PMID- 27483086
TI - The Use of CAD/CAM Technology for Fabricating Cast Gold Survey Crowns under
Existing Partial Removable Dental Prosthesis. A Clinical Report.
AB - The fabrication of a survey crown under an existing partial removable dental
prosthesis (PRDP) has always been a challenge to many dental practitioners. This
clinical report presents a technique for fabricating accurate cast gold survey
crowns to fit existing PRDPs using CAD/CAM technology. The report describes a
technique that would digitally scan the coronal anatomy of a cast gold survey
crown and an abutment tooth under existing PRDPs planned for restoration, prior
to any preparation. The information is stored in the digital software where all
the coronal anatomical details are preserved without any modifications. The
scanned designs are then applied to the scanned teeth preparations, sent to the
milling machine and milled into full-contour clear acrylic resin burn-out
patterns. The acrylic resin patterns are tried in the patient's mouth the same
day to verify the full seating of the PRDP components. The patterns are then
invested and cast into gold crowns and cemented in the conventional manner.
PMID- 27483087
TI - Reply.
PMID- 27483088
TI - Impact of Rheumatoid Arthritis on the Mortality of Elderly Patients Who Develop
Cancer: A Population-Based Study.
AB - OBJECTIVE: Comorbidity among cancer patients poses additional risks for
mortality. The possible impact of rheumatoid arthritis (RA) on cancer patient
survival is unclear. Our objective was to examine survival among elderly patients
with RA who develop cancer. METHODS: Patients diagnosed with breast, prostate,
colorectal, or lung cancer between 2001 and 2010 were identified from the Texas
Cancer Registry and Medicare-linked databases. The cohort was categorized into 3
groups according to the number of claims patients had with a diagnosis of RA in
the year prior to the cancer diagnosis: 2-RA (patients with >=2 claims), 1-RA (1
claim), and no claims. Overall survival was estimated for these groups and for
each cancer, using Cox proportional hazards models adjusting for covariates.
RESULTS: The cohort included 139,097 patients with cancer (35,026 breast, 43,181
prostate, 31,103 colorectal, and 29,787 lung); 1.7% had 1 RA claim, and 1.1% had
2 or more. Adjusted hazard ratios for patients in the 2-RA group were 1.41 (95%
confidence interval [95% CI] 1.21-1.65) for breast and 1.53 (95% CI 1.26-1.85)
for prostate. No significant differences were observed for those with colorectal
or lung cancer. CONCLUSION: Mortality was increased by 40% and 50%, respectively,
in elderly patients with RA who developed breast or prostate cancer, after
controlling for other comorbidities. This association was not seen in cancers
with shorter survival time (colorectal or lung). Research is needed to determine
whether the increased risk is related to comorbid burden or to differential
utilization of cancer or rheumatoid therapies in patients with both diseases.
PMID- 27483089
TI - First-Trimester Diagnosis of Congenital Diaphragmatic Hernia.
PMID- 27483090
TI - Synthesis of Spherical Carbon Nitride-Based Polymer Composites by Continuous
Aerosol-Photopolymerization with Efficient Light Harvesting.
AB - Here we report a novel, facile, and sustainable approach for the preparation of
spherical submicrometer carbon nitride-based polymer composites by a continuous
aerosol-photopolymerization process. In this regard, spherical mesoporous carbon
nitride (SMCN) nanoparticles were initially prepared via a nanocasting approach
using spray-drying synthesized spherical mesoporous silica (SMS) nanoparticles as
hard templates. In addition to experimental characterization, the effect of
porosity on the light absorption enhancement and consequently the generation rate
of electron-hole pairs inside the SMCN was simulated using a three-dimensional
finite difference time-domain (FDTD) method. To produce the carbon nitride-based
polymer composite, SMCN nanoparticles exhibit excellent performance in
photopolymerization of butyl acrylate (PBuA) monomer in the presence of n
methyldiethanolamine (MDEA) as a co-initiator in a continuous aerosol-based
process. In this one-pot synthesis, SMCN nanoparticles act not only as
photoinitiators but at the same time as fillers and templates. The average
aerosol residence time in the photoreactor is about 90 s. The presented aerosol
photopolymerization process avoids the need for solvent and surfactant, operates
at room temperature, and, more importantly, is suitable to produce the spherical
composite with hydrophobic polymers. Furthermore, we simulated the condition of
SMCN nanoparticles during illumination in the gas phase process, which can freely
rotate. The results demonstrated that the hole (h(+)) density is almost equally
distributed in the whole part of the SMCN nanoparticles due to their rotation,
leading to efficient light harvesting and more homogeneous photoreaction. The
combination of the outstanding features of environmentally friendly SMCN,
photopolymerization, and aerosol processing might open new avenues, especially in
green chemistry, to produce novel polymer composites with multifunctional
properties.
PMID- 27483091
TI - Halo-Type Distraction Device Used to Treat a Severe Midface Depression Fracture.
AB - The deep layers of the nasoethmoid region comprise a thin-walled lacrimal bone, a
paper-thin ethmoid plate, and ethmoidal cells, forming an extremely fragile and
easily crushed structure. In a nasoethmoid complex fracture where the support
structure itself is destroyed, epithesis and immobilization are difficult and can
lead to residual saddle nose deformities. Therefore, bone grafts are often
necessary at a later date. Recently, the authors occasionally see reports of
nasoethmoid complex fractures that are treated with Halo distraction devices.
Advantages of this device are that it applies constant traction to maintain the
shape of the structures until the ruptured nasoethmoid bone and mucosa are
repaired, thus minimizing relapse. There is no need for rigid fixation with a
plate, no limitations on how much distraction is possible, and no major skin
incisions are required for the approach. The authors treated a 30-year-old man
who suffered a severe and widespread depressed facial deformation due to a
nasoethmoid fracture that included a midface comminuted fracture using a Halo
type distraction device. A gentle traction was maintained on the nasoethmoid bone
and part of the maxilla pulling it forward, and resulted in an extremely good
outcome both esthetically and functionally. This method is believed to be
extremely useful and effective, requiring only minimally invasive surgery for
comminuted midface fractures involving a nasoethmoid fracture with a depressed
frontal process of the maxilla. Below, the authors provide a detailed description
of their experience with this device.
PMID- 27483092
TI - Penetrating Neck Injury Remnant Mimicking Chronic Cutaneous Neck Fistula.
PMID- 27483093
TI - Assessment of Smell Function in Syndromic Craniosynostosis Patients.
AB - Craniosynostosis is defined as premature fusion of the cranial suture lines and
is part of a syndrome in 15% to 40% of the patients. There is limited literature
available regarding these children's ability to smell. Most of them will undergo
numerous surgical procedures, some of which may alter their sense of smell,
potentially leading to significant social as well as safety implications. Ethical
approval was obtained for this pilot study. Children with syndromic
craniosynostosis were recruited and underwent anterior rhinoscopy, prior to
performing a smell test utilizing the Sensonic pediatric Smell wheel. The results
were compared to an age-matched control group. Eight children with syndromic
craniosynostosis participated in the study. Of a possible total score of 11,
their mean average score was 6.6 and the median was 6. In comparison, the mean
average score for the control group was 7.5 and the median was 7. Although the
study group was small, this pilot study demonstrates that children with syndromic
craniosynostosis have a similar ability to identify smells to an age-matched
cohort. Further research can now be undertaken to see whether or not midface
advancement procedures affect these children's sense of smell.
PMID- 27483094
TI - Symptomatic Giant Lipoma Under the Latissimus Muscle.
AB - Lipoma is a common benign tumor derived from stroma that can arise in any
location where fat is normally present. Giant lipoma is defined as a lesion that
is >10 cm in length and weighs >1000 g. Axillary region might have been exposed
to microtraumas with each movement of upper extremity, leading to the development
of giant lipoma. In this report, a 56-year-old man visited us because of a soft
tissue mass on the left axilla that had been noticed 5 years before. We removed
the tumor from the patient under general anesthesia. A lipoma measuring 21 cm *
12 cm in size was removed, and the weight of the mass was 455 g. The case of our
patient is very interesting because there have been few reported patients with a
diagnosis of a giant lipoma in a sublatissimusdorsi muscle.
PMID- 27483095
TI - Overcorrection of a Medial Orbital Wall Fracture Using the Endonasal Approach.
AB - Although the endonasal approach is frequently used, and the inadvertent
displacement of a bone fragment into the orbital cavity is possible, no reports
have yet described the overcorrection of medial orbital wall fractures using the
endonasal approach. The authors report 2 patients of the overcorrection of a
medial orbital wall fracture using an endonasal approach.In the first patient, a
26-year-old Chinese-Korean woman experienced a fracture of the right medial
orbital wall without entrapment of the medial rectus muscle. Eleven days after
the trauma, endonasal reduction was performed. Postoperative computed tomography
revealed overcorrection of the medial orbital wall and lateral displacement of
the medial rectus muscle. On postoperative day 19, exophthalmos of the operated
side was still observed (o.d. 20 mm/o.s. 17 mm). In the second patient, a 25-year
old Korean man experienced a fracture of the left medial orbital wall without
entrapment of the medial rectus muscle. Postoperative computed tomography showed
overcorrection of the medial orbital wall and a laterally displaced medial rectus
muscle. On postoperative day 4, exophthalmos of the operated side was observed
(o.d. 23 mm/o.s. 26 mm).For fractures of the medial wall, surgery should be
performed according to the recommended indications. When the endonasal approach
is used to treat medial orbital wall fractures, great care is required in
reducing the herniated orbital tissue and inserting the sheet to avoid
overcorrection.
PMID- 27483096
TI - Orbital Rehabilitation Implant-Retained: An Alternative to Adhesives Cutaneous
Hypersensitivity.
PMID- 27483097
TI - Muscle Tension Line Groups Reconstruction in Bilateral Cleft Lip Repair.
AB - BACKGROUND: Bilateral cleft lip is considered to be the most difficult cleft lip
to repair. More and more surgeries are concerned about the reconstruction of
orbicularis muscle and the pursuit of philtrum shaping in bilateral cleft lip
repair, but most have little success. Years of study on the orbicularis muscle of
children with cleft lip resulted in authors' creation of muscle tension line
groups theory. Through implementation of this theory, the authors have achieved
favorable results in microform cleft lip repair. The authors also applied this
concept to bilateral cleft lip repair. METHODS: Between January 2010 and December
2014, 31 children with bilateral cleft lip received operations in authors'
department, and underwent muscle tension line group reconstruction in accordance
with the theory of muscle tension line groups. Two third-party doctors judged
postoperative results using a 3-point visual analogue scale. RESULTS: Twenty-two
of the 31 children completed a follow-up 6 months to 1 year after surgery. Most
postoperative and follow-up results were satisfactory. CONCLUSION: Fully
reconstructed muscle tension line groups can not only assist with close
fractures, but, for example, also help adduct the nasal alar, and elevate the
nasal floor. Furthermore, the surgery can be used to reconstruct the 3
dimensional structure of the philtrum. Ultimately, surgical application of the
muscle tension line groups theory proved its feasibility and potential for
further development.
PMID- 27483098
TI - Caudal Septal Stabilization Suturing Technique to Treat Crooked Noses.
AB - AIM: To rotate the nasal axis and septum to the midline using an L-strut graft
and a novel caudal septal stabilization suturing technique to treat crooked
noses. PATIENTS AND METHODS: Thirty-six patients were included in the study.
First, an L-strut graft was prepared by excising the deviated cartilage site in
all patients. Second, multiple stabilization suturing, which we describe as a
caudal septal stabilization suturing technique with a "fishing net"-like
appearance, was applied between the anterior nasal spine and caudal septum in all
patients. This new surgical technique, used to rotate the caudal septum, was
applied to 22 I-type and 14 C-type crooked noses. Correction rates for the
crooked noses were compared between the 2 inclination types with angular
estimations. RESULTS: Deviation angles were measured using the AutoCAD 2012
software package and frontal (anterior) views, with the Frankfurt horizontal line
parallel to the ground. Nasal axis angles showing angle improvement graded 4
categories as excellent, good, acceptable, and unsuccessful for evaluations at 6
months after surgery in the study. The success rate in the C-type nasal
inclination was 86.7% (+/-21.9) and 88% (+/-16.7) in the I-type. The overall
success rate of L-strut grafting and caudal septal stabilization suturing in
crooked nose surgeries was 87.5% (+/-18.6). "Unsuccessful" results were not
reported in any of the patients. CONCLUSIONS: L-strut grafting and caudal septal
stabilization suturing techniques are efficacious in crooked noses according to
objective measurement analysis results. However, a longer follow-up duration in a
larger patient population is needed.
PMID- 27483099
TI - Traumatic Fracture of the Premaxilla in the Bilateral Cleft Patient.
AB - Traumatic fracture of the premaxilla is a rare event, and there is minimal data
regarding the presentation, management, and outcome of these patients. This
article reports 2 patients with bilateral cleft lip and palate who each presented
with traumatic fracture and displacement of the premaxilla. To authors'
knowledge, the occurrence and management of a traumatic fracture and displacement
of the premaxilla in a patient with cleft lip and palate has not been reported.
PMID- 27483100
TI - Descriptive Analysis of Sphenovomerine Suture and Its Importance in Neurosurgery.
AB - PURPOSE: Articulation of rostrum of sphenoid bone with alae of vomer forms a
schindylesis type of joint. The circumference of this joint, called
sphenovomerine suture (SVS), is very important in establishing a reliable
surgical field in the endoscopic transsphenoidal pituitary surgery. Because of
its vital role in endoscopic transsphenoidal pituitary surgery, this radio
anatomical study was designed to establish the morphological properties of SVS.
METHODS: In this study, the authors examined SVS in 235 patients (121 females and
114 males) on the computed tomography images of the paranasal sinus and made 4
measurements to describe SVS. RESULTS: The mean distance between superior margin
of the upper labial philtrum and top of SVS was 6.66 +/- 0.43 cm for females and
7.44 +/- 0.54 cm for males. The distance between the top of SVS and dorsum sellae
was 3.08 +/- 0.33 cm for females and 3.19 +/- 0.32 cm for males, the alae of
vomer angle in the upper surface was 74.22 +/- 20.06 degrees for females and
74.23 +/- 19.68 degrees for males. The distance between the most lateral points
of 2 alae of vomer was 0.99 +/- 0.17 and 1.01 +/- 0.19 cm for females and males,
respectively. CONCLUSIONS: For an easy and successful operation, removal of the
SVS is very important as it will provide a better view of the sellar base and
make the management of the surgical instruments easier in the wider safe surgical
field thus created.
PMID- 27483101
TI - Sunken Eye Induced by Superior Orbital Wall Defect After Craniofacial Surgery.
AB - Enophthalmos after a ventriculo-peritoneal (V-P) shunt placement is very rare.
Previous defects of the orbital wall with intracranial hypotension can cause
enophthalmos after V-P shunting. The authors present 2 patients of enophthalmos
with orbital wall defects resulting from anterior clinoidectomy that was
performed during previous aneurysmal surgery. Both patients received a V-P shunt
for hydrocephalus after subarachnoid hemorrhage. Although the hydrocephalus was
improved by V-P shunts in both patients, sunken eyes were observed. The patients
received reconstructive surgery of the superior orbital wall using titanium mesh
and recovered after surgery without any neurological deficits. Here, the authors
present 2 patients of enophthalmos with orbital wall defects treated by orbital
wall reconstruction.
PMID- 27483102
TI - A Rare Case of Unilateral Isolated Naso-Ocular Cleft Treated by a Rotation
Advancement Technique.
AB - The isolated naso-ocular cleft is rare. In this article, the authors report an
extremely rare case of unilateral isolated naso-ocular cleft. And a new rotation
advancement technique was used in repair. Result was satisfied, especially the
esthetical scar location. But if an upper lid flap was performed simultaneously,
the result should be better.
PMID- 27483103
TI - Lobular Capillary Hemangioma Originating From the Posterior Portion of the
Inferior Turbinate.
PMID- 27483104
TI - The Surgical Strategy for the Intraorbital Foreign Bodies.
AB - PURPOSE: Four patients with intraorbital foreign bodies admitting to our clinic
between 2001 and 2011 are presented. Their clinical and radiologic findings and
surgical strategies are discussed. OBJECTIVE: The success of surgery for the
intraorbital foreign bodies largely depends on the determination of the exact
localization of them. Radiologic examination should follow clinical diagnosis.
Computed tomographic views are especially required to demonstrate the foreign
body. MATERIALS AND METHODS: Four patients with different etiologies of trauma
are presented. Each had computed tomography views for foreign body localization.
All but 1 had surgery for removal of the object under general anesthesia.
RESULTS: No complications were observed postoperatively. Only 1 patient is
followed up without an operation due to the risk of damaging delicate structures
that the foreign body is close to. He has no loss of function. CONCLUSION: Early
removal of foreign bodies in orbital region is usually preferred due to the risk
of neurologic damage and other complications. Surgical removal is quite
challenging for foreign bodies like wood. Magnets can be used for metallic
bodies.
PMID- 27483105
TI - Nasal Tip Schwannoma Coexisting With Vestibular Schwannoma.
AB - Although a schwannoma can originate from any central or peripheral nerves,
schwannomas originating from the nasal tip are extremely rare and only 4 cases
have been reported so far in English literature. These 4 cases appeared solely
without any other accompanying schwannomas. However, the authors recently treated
a patient with a nasal tip schwannoma coexisting with vestibular schwannoma. The
nasal tip schwannoma was successfully removed without cosmetic deformity by using
an open rhinoplasty approach.
PMID- 27483106
TI - Orbital Fat Prolapse Into the Nasal Cavity in Orbital Blowout Fracture.
AB - In this study, the authors describe the first report of 2 patients of fat
prolapse into the nasal cavity by orbital blowout fracture. The patients were a
58-year-old male and an 86-year-old female. The patients could not attain
binocular single vision in any eye position because of severe impairment of the
extraocular muscle motility. Computed tomographic images of both patients
revealed orbital blowout fractures with orbital fat prolapse into the nasal
cavity. The fractures were reduced under transconjunctival/transcaruncular and
endonasal endoscopic approaches. Six months postoperatively, the patients
attained a binocular single vision field, including in the primary eye position.
PMID- 27483107
TI - Oral Lesions in Pycnodysostosis Syndrome: Eleven Years of Follow-Up.
AB - Pycnodysostosis is a rare genetic disease that is characterized by
osteosclerosis, short stature, and bone fragility. There are not cases of gnathic
bones lesions reported on the international literature. This study aims to
describe a clinical case of a 10-year-old girl with pycnodysostosis syndrome and
an uncommon association with 4 distinct lesions (dentigerous cyst, central giant
cell lesions, and 2 fibro-osseous lesions).
PMID- 27483108
TI - Dumbbell-Shaped Epidural Cavernous Hemangioma in the Thoracic Spine Mimicking
Schwannoma.
AB - Dumbbell-shaped epidural cavernous hemangiomas (CHs) are extremely rare, and they
are easily misdiagnosed as spinal schwannomas. Herein, the authors report 1 rare
case of dumbbell-shaped epidural CH in the thoracic spine. To the best of our
knowledge, only a few cases of dumbbell-shaped epidural CHs in thoracic spine
have been reported. Furthermore, the clinical characteristics and treatments for
spinal epidural CHs were investigated and reviewed.
PMID- 27483109
TI - Membrane Compartmentalization Reducing the Mobility of Lipids and Proteins within
a Model Plasma Membrane.
AB - The cytoskeleton underlying cell membranes may influence the dynamic organization
of proteins and lipids within the bilayer by immobilizing certain transmembrane
(TM) proteins and forming corrals within the membrane. Here, we present coarse
grained resolution simulations of a biologically realistic membrane model of
asymmetrically organized lipids and TM proteins. We determine the effects of a
model of cytoskeletal immobilization of selected membrane proteins using long
time scale coarse-grained molecular dynamics simulations. By introducing
compartments with varying degrees of restraints within the membrane models, we
are able to reveal how compartmentalization caused by cytoskeletal immobilization
leads to reduced and anomalous diffusional mobility of both proteins and lipids.
This in turn results in a reduced rate of protein dimerization within the
membrane and of hopping of membrane proteins between compartments. These
simulations provide a molecular realization of hierarchical models often invoked
to explain single-molecule imaging studies of membrane proteins.
PMID- 27483110
TI - The effects of different types of ankle-foot orthoses on postural responses in
individuals with walking impairments.
AB - The aim of this study was to examine the immediate and long-term effects of
different ankle-foot orthosis (AFO) types on postural responses in patients with
various pathological conditions who, because of their walking disorders, wore an
AFO. A total of 37 patients with different pathological conditions who visited
the outpatient clinic for orthotics because of walking problems, already used or
were referred for an AFO and had no other impairments that may influence balance
were included in the study. The participants were divided into four groups
according to the type of AFO that they wore. The postural responses were assessed
with and without AFO using two force-plates following perturbations in different
directions at the level of the pelvis. The centre of pressure was examined in the
sagittal and frontal plane and compared with the normative data from healthy
individuals. The results showed an improvement in postural responses to the
lateral and backward perturbation directions when wearing the AFO, particularly
responses in the anterior-posterior direction. The best results were achieved
with the custom-made posterior leaf spring AFO for correction of equinovarus
deformity. The time of wearing the AFO had an impact on postural responses in
perturbation directions where the patients could not rely only on AFO. The custom
made AFO improved overall postural responses, especially dynamic stability, in
lateral directions, whereas all stiff AFOs contributed towards an improvement in
responses to all perturbations to the affected side. Results showed that long
term use of an AFO can be important for the overall improvement of postural
responses.
PMID- 27483111
TI - Adolf Meyer: His Achievements and Legacy.
AB - This lecture, given to celebrate the centennial of the founding of the Henry
Phipps Psychiatric Service at Johns Hopkins, addresses the career and
contributions to psychiatry and neurology of Adolf Meyer, the first Phipps
Professor. It reviews his achievements historically describing the bleak clinical
situation of psychiatry when he began as a neuropathologist at Kankakee Hospital
in Illinois in 1892, what he did to address them, the sources of help he found
and exploited from leading figures in the emerging Progressive Era (1890-1917) in
American life, and how he confronted and overcame resistances to his empirical,
psychobiological conceptions of mental illness as he advanced. His legacy is
reflected in the signal contributions of four leaders of American psychiatry
(Drs. Leo Kanner, Alexander Leighton, Jerome Frank, and Paul Lemkau) who had been
his residents and in those aspects of contemporary teaching and research at
Hopkins that reflect his thought.
PMID- 27483112
TI - Profiles of Depression Help Seeking Among Black Americans: A Latent Class
Approach.
AB - Although Black Americans have lower prevalence of depression compared to non
Hispanic Whites (10% vs. 17%), they are nearly twice as likely to have worse
outcomes. One contributor to poor depression outcomes involves the ways in which
Black Americans seek help for depression. However, little is known about
depression help-seeking behavior, and the use of multiple sources of help, among
Black Americans. This study used latent class analysis to identify unique
constellations of depression help seeking, from multiple sources, among African
American and Black Caribbeans. Results indicated four profiles of depression help
seeking including Informal/Primary Care Utilizers (41.4%), Formal Mental Health
Utilizers (40.6%), All Support Utilizers (9.8%), and Mixed Source Utilizers
(8.2%). The constellation of each profile and demographic differences in class
assignment are discussed. Results have implications for tailored depression
interventions for Black Americans including community-based psychoeducation and
cultural competence training for mental health providers.
PMID- 27483113
TI - Psychiatric Disorders and Predictors Hereof Among Refugee Children in Early
Adulthood: A Register-Based Cohort Study.
AB - Studies show a high level of mental health problems among refugee children and
adults. This study aimed to examine psychiatric disorders among refugee children
in early adulthood. A total of 15,264 young adult refugees, who obtained
residence permission January 1, 1993 to December 31, 2010, were matched 1:6 on
age and sex with 99,313 Danish-born children. Rate ratios (RR) of having a first
time in- or outpatient hospital diagnosis with an affective (F30-39), psychotic
(F29-30), neurotic (F40-48), or any psychiatric disorder (F00-99) according to
ICD-10 were computed. Refugees had higher RRs of psychotic (RR: 1.81, 95%CI: 1.41
2.32) and nervous (RR: 1.28, 95% CI: 1.14-1.43) disorders compared with Danish
born children. The RRs of having an affective disorder among refugees was 0.74
(95% CI: 0.60-0.90) compared with Danish-born children. Sex, geographical origin,
migrant status, household income, age at residence permission, and
accompanied/unaccompanied arrival predicted psychiatric contacts among refugees.
A focus on both prevention and treatment in vulnerable groups is needed.
PMID- 27483114
TI - Sensory Gating Deficits in First-Episode Psychosis: Evidence From
Neurophysiology, Psychophysiology, and Neuropsychology.
AB - Sensory gating deficits are commonly found in patients with schizophrenia.
However, there is still scarce research on this issue. Thirty-eight patients with
first-episode psychosis (FEP) were compared to thirty-eight controls. A condition
test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and
some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used
(i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention
and vigilance). The ERP components measured were P50, N1, and P2. The PPI
intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing
speed and attention/vigilance cognitive domains were selected. FEP patients
showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and
in all the MCCB subtests selected. We obtained significant relationships in N1
with PPI-60, and with one MCCB subtest for processing speed. In addition, this
same subtest showed significant association with P2. Therefore, sensory gating
functioning is widely impaired since the very early stages of schizophrenia.
PMID- 27483115
TI - Electrical conductivity of oxidized-graphenic nanoplatelets obtained from bamboo:
effect of the oxygen content.
AB - The large-scale production of graphene and reduced-graphene oxide (rGO) requires
low-cost and eco-friendly synthesis methods. We employed a new, simple, cost
effective pyrolytic method to synthetize oxidized-graphenic nanoplatelets (OGNP)
using bamboo pyroligneous acid (BPA) as a source. Thorough analyses via high
resolution transmission electron microscopy and electron energy-loss spectroscopy
provides a complete structural and chemical description at the local scale of
these samples. In particular, we found that at the highest carbonization
temperature the OGNP-BPA are mainly in a sp(2) bonding configuration (sp(2)
fraction of 87%). To determine the electrical properties of single nanoplatelets,
these were contacted by Pt nanowires deposited through focused-ion-beam-induced
deposition techniques. Increased conductivity by two orders of magnitude is
observed as oxygen content decreases from 17% to 5%, reaching a value of 2.3 *
10(3) S m(-1) at the lowest oxygen content. Temperature-dependent conductivity
reveals a semiconductor transport behavior, described by the Mott three
dimensional variable range hopping mechanism. From the localization length, we
estimate a band-gap value of 0.22(2) eV for an oxygen content of 5%. This
investigation demonstrates the great potential of the OGNP-BPA for technological
applications, given that their structural and electrical behavior is similar to
the highly reduced rGO sheets obtained by more sophisticated conventional
synthesis methods.
PMID- 27483116
TI - [Not Available].
PMID- 27483117
TI - [Not Available].
PMID- 27483118
TI - [Not Available].
PMID- 27483119
TI - [Not Available].
PMID- 27483120
TI - [Not Available].
PMID- 27483121
TI - Mixotrophy in the Marine Plankton.
AB - Mixotrophs are important components of the bacterioplankton, phytoplankton,
microzooplankton, and (sometimes) zooplankton in coastal and oceanic waters.
Bacterivory among the phytoplankton may be important for alleviating inorganic
nutrient stress and may increase primary production in oligotrophic waters.
Mixotrophic phytoflagellates and dinoflagellates are often dominant components of
the plankton during seasonal stratification. Many of the microzooplankton
grazers, including ciliates and Rhizaria, are mixotrophic owing to their
retention of functional algal organelles or maintenance of algal endosymbionts.
Phototrophy among the microzooplankton may increase gross growth efficiency and
carbon transfer through the microzooplankton to higher trophic levels.
Characteristic assemblages of mixotrophs are associated with warm, temperate, and
cold seas and with stratification, fronts, and upwelling zones. Modeling has
indicated that mixotrophy has a profound impact on marine planktonic ecosystems
and may enhance primary production, biomass transfer to higher trophic levels,
and the functioning of the biological carbon pump.
PMID- 27483122
TI - N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed
in silico with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and
breast cancer cells.
AB - Epigenetic alterations are associated with cancer and their targeting is a
promising approach for treatment of this disease. Among current epigenetic drugs,
histone deacetylase (HDAC) inhibitors induce changes in gene expression that can
lead to cell death in tumors. Valproic acid (VPA) is a HDAC inhibitor that has
antitumor activity at mM range. However, it is known that VPA is a hepatotoxic
drug. Therefore, the aim of this study was to design a set of VPA derivatives
adding the arylamine core of the suberoylanilide hydroxamic acid (SAHA) with
different substituents at its carboxyl group. These derivatives were submitted to
docking simulations to select the most promising compound. The compound 2 (N-(2
hydroxyphenyl)-2-propylpentanamide) was the best candidate to be synthesized and
evaluated in vitro as an anti-cancer agent against HeLa, rhabdomyosarcoma and
breast cancer cell lines. Compound 2 showed a better IC50 (MUM range) than VPA
(mM range) on these cancer cells. And also, 2 was particularly effective on
triple negative breast cancer cells. In conclusion, 2 is an example of drugs
designed in silico that show biological properties against human cancer difficult
to treat as triple negative breast cancer.
PMID- 27483123
TI - Network-level Mechanisms of Ketamine Anesthesia.
PMID- 27483124
TI - Success of Intubation Rescue Techniques after Failed Direct Laryngoscopy in
Adults: A Retrospective Comparative Analysis from the Multicenter Perioperative
Outcomes Group.
AB - BACKGROUND: Multiple attempts at tracheal intubation are associated with
mortality, and successful rescue requires a structured plan. However, there
remains a paucity of data to guide the choice of intubation rescue technique
after failed initial direct laryngoscopy. The authors studied a large
perioperative database to determine success rates for commonly used intubation
rescue techniques. METHODS: Using a retrospective, observational, comparative
design, the authors analyzed records from seven academic centers within the
Multicenter Perioperative Outcomes Group between 2004 and 2013. The primary
outcome was the comparative success rate for five commonly used techniques to
achieve successful tracheal intubation after failed direct laryngoscopy: (1)
video laryngoscopy, (2) flexible fiberoptic intubation, (3) supraglottic airway
as part of an exchange technique, (4) optical stylet, and (5) lighted stylet.
RESULTS: A total of 346,861 cases were identified that involved attempted
tracheal intubation. A total of 1,009 anesthesia providers managed 1,427 cases of
failed direct laryngoscopy followed by subsequent intubation attempts (n = 1,619)
that employed one of the five studied intubation rescue techniques. The use of
video laryngoscopy resulted in a significantly higher success rate (92%; 95% CI,
90 to 93) than other techniques: supraglottic airway conduit (78%; 95% CI, 68 to
86), flexible bronchoscopic intubation (78%; 95% CI, 71 to 83), lighted stylet
(77%; 95% CI, 69 to 83), and optical stylet (67%; 95% CI, 35 to 88). Providers
most frequently choose video laryngoscopy (predominantly GlideScope [Verathon,
USA]) to rescue failed direct laryngoscopy (1,122/1,619; 69%), and its use has
increased during the study period. CONCLUSIONS: Video laryngoscopy is associated
with a high rescue intubation success rate and is more commonly used than other
rescue techniques.
PMID- 27483125
TI - Avoiding Repeated Attempts at Tracheal Intubation: Can Videolaryngoscopes Be the
Answer?
PMID- 27483126
TI - Contribution of the Suppressor of Variegation 3-9 Homolog 1 in Dorsal Root
Ganglia and Spinal Cord Dorsal Horn to Nerve Injury-induced Nociceptive
Hypersensitivity.
AB - BACKGROUND: Peripheral nerve injury-induced gene alterations in the dorsal root
ganglion (DRG) and spinal cord likely participate in neuropathic pain genesis.
Histone methylation gates gene expression. Whether the suppressor of variegation
3-9 homolog 1 (SUV39H1), a histone methyltransferase, contributes to nerve injury
induced nociceptive hypersensitivity is unknown. METHODS: Quantitative real-time
reverse transcription polymerase chain reaction analysis, Western blot analysis,
or immunohistochemistry were carried out to examine the expression of SUV39H1
mRNA and protein in rat DRG and dorsal horn and its colocalization with DRG MU
opioid receptor (MOR). The effects of a SUV39H1 inhibitor (chaetocin) or SUV39H1
siRNA on fifth lumbar spinal nerve ligation (SNL)-induced DRG MOR down-regulation
and nociceptive hypersensitivity were examined. RESULTS: SUV39H1 was detected in
neuronal nuclei of the DRG and dorsal horn. It was distributed predominantly in
small DRG neurons, in which it coexpressed with MOR. The level of SUV39H1 protein
in both injured DRG and ipsilateral fifth lumbar dorsal horn was time dependently
increased after SNL. SNL also produced an increase in the amount of SUV39H1 mRNA
in the injured DRG (n = 6/time point). Intrathecal chaetocin or SUV39H1 siRNA as
well as DRG or intraspinal microinjection of SUV39H1 siRNA impaired SNL-induced
allodynia and hyperalgesia (n = 5/group/treatment). DRG microinjection of SUV39H1
siRNA also restored SNL-induced DRG MOR down-regulation (n = 6/group).
CONCLUSIONS: The findings of this study suggest that SUV39H1 contributes to nerve
injury-induced allodynia and hyperalgesia through gating MOR expression in the
injured DRG. SUV39H1 may be a potential target for the therapeutic treatment of
nerve injury-induced nociceptive hypersensitivity.
PMID- 27483127
TI - Sedation with Dexmedetomidine or Propofol Impairs Hypoxic Control of Breathing in
Healthy Male Volunteers: A Nonblinded, Randomized Crossover Study.
AB - BACKGROUND: In contrast to general anesthetics such as propofol, dexmedetomidine
when used for sedation has been put forward as a drug with minimal effects on
respiration. To obtain a more comprehensive understanding of the regulation of
breathing during sedation with dexmedetomidine, the authors compared ventilatory
responses to hypoxia and hypercapnia during sedation with dexmedetomidine and
propofol. METHODS: Eleven healthy male volunteers entered this randomized
crossover study. Sedation was administered as an intravenous bolus followed by an
infusion and monitored by Observer's Assessment of Alertness/Sedation (OAA/S)
scale, Richmond Agitation Sedation Scale, and Bispectral Index Score. Hypoxic and
hypercapnic ventilatory responses were measured at rest, during sedation (OAA/S 2
to 4), and after recovery. Drug exposure was verified with concentration analysis
in plasma. RESULTS: Ten subjects completed the study. The OAA/S at the sedation
goal was 3 (3 to 4) (median [minimum to maximum]) for both drugs. Bispectral
Index Score was 82 +/- 8 and 75 +/- 3, and the drug concentrations in plasma at
the sedation target were 0.66 +/- 0.14 and 1.26 +/- 0.36 MUg/ml for
dexmedetomidine and propofol, respectively. Compared with baseline, sedation
reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82
and 86% for dexmedetomidine and propofol, respectively. In addition, some
volunteers displayed upper airway obstruction and episodes of apnea during
sedation. CONCLUSIONS: Dexmedetomidine-induced sedation reduces ventilatory
responses to hypoxia and hypercapnia to a similar extent as sedation with
propofol. This finding implies that sedation with dexmedetomidine interacts with
both peripheral and central control of breathing.
PMID- 27483128
TI - Anesthesiologists and Healthcare Redesign: Time to Team Up with Experts.
PMID- 27483129
TI - Pharmacokinetic Studies of Sustained-Release Depot of Dexamethasone in Beagle
Dogs.
AB - PURPOSE: To examine the pharmacokinetic characteristics of sustained-release
dexamethasone depots in two separate canine studies. METHODS: Dexamethasone
depots loaded with a clinically representative (0.4 mg) dose (DEXTENZATM; Ocular
Therapeutix) or an elevated (0.7 mg) dose were inserted into the canaliculi of
beagle eyes (n = 37 and n = 34, respectively). Tear fluid was collected for
pharmacokinetic analysis of dexamethasone in both studies at predetermined time
points. Explanted 0.4 mg depots were collected weekly to measure remaining drug
level. Clinical observations and ophthalmic examinations were performed in both
studies at each visit. RESULTS: The 0.4 mg depots released a median 308 MUg by
day 15 and tapered to complete drug release by day 28. Median dexamethasone tear
fluid concentrations in the 0.4 mg study group decreased from 2,805 ng/mL at day
7 to 0 ng/mL on day 28. Median dexamethasone tear fluid concentrations in the 0.7
mg study group decreased from 4,370 ng/mL at 6 h post insertion to 830 ng/mL on
day 35. Mean +/- standard deviation intraocular pressures in the 0.4 and 0.7 mg
study groups were 20.7 +/- 2.8 and 19.0 +/- 4.1 mmHg at baseline, respectively,
and demonstrated no meaningful change (20.5 +/- 3.0 and 20.6 +/- 2.9 mmHg,
respectively) over the studies' durations. No ocular toxicities were attributed
to the dexamethasone depot. CONCLUSION: Sustained-release dexamethasone produced
no identifiable ocular toxicity in this animal model, and pharmacokinetics
demonstrated a sustained and tapered drug release over 28 days at a 0.4 mg dose
and exceeded 35 days at a 0.7 mg dose.
PMID- 27483130
TI - Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and
Combination Therapy for Attention-Deficit/Hyperactivity Disorder.
AB - OBJECTIVES: This study examines cardiovascular (CV) effects of guanfacine
immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and
their combination (COMB) during acute and long-term treatment of youth with
attention-deficit/hyperactivity disorder. METHODS: Two hundred seven participants
aged 7-14 years enrolled in an 8-week double-blind randomized trial of GUAN-IR (1
3 milligrams (mg)/day), DMPH (5-20 mg/day), or COMB with fixed-flexible dosing
and titrated to optimal behavioral response. Heart rate, systolic blood pressure
(BP), diastolic BP, and electrocardiograms were assessed at baseline, end of
blinded optimization, and over a 1-year open-label maintenance phase. RESULTS:
During acute titration, GUAN-IR decreased heart rate, systolic BP, and diastolic
BP; DMPH increased heart rate, systolic BP, diastolic BP, and corrected QT (QTc)
interval; COMB increased diastolic BP, but had no effects on heart rate, systolic
BP, or QTc. During maintenance, GUAN-IR-associated decreases in heart rate and
DMPH-associated increases in systolic BP returned to baseline values. Other
variables across the three groups remained unchanged from the end of blinded
titration. There were no discontinuations due to CV adverse events. CONCLUSION:
GUAN-IR, DMPH, and COMB were well tolerated and safe. Expected changes in CV
parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB
values falling intermediately between the two other treatment groups. No serious
CV events occurred in any participant. GUAN-IR- and DMPH-associated CV changes
generally returned to baseline with sustained therapy. These data suggest that
COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant
monotherapy, possibly reducing risk of the small but statistically significant
changes associated with either single treatment. Clinicaltrials.gov Identifier:
NCT00429273.
PMID- 27483131
TI - Multiple metrics quantify and differentiate responses of vegetation to
composition B.
AB - Quantifying vegetation response to explosive compounds has focused predominantly
on morphological impacts and uptake efficiency. A more comprehensive
understanding of the total impacts of explosives on vegetation can be gained
using a multivariate approach. We hypothesized that multiple variables
representing morphological and physiological responses will more clearly
differentiate species and treatments than any single variable. Individuals of
three plant species were placed in soils contaminated with Composition B, which
comprises 60% hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 40% 2,4,6
trinitrotoluene (TNT), and grown for 2 months. Response metrics used included
photosynthetic operation, water relations, growth characteristics, as well as
nitrogen and carbon concentrations and isotopic compositions. Individual metrics
showed high variability in response across the three species tested. Water
relations and nitrogen isotopic composition exhibited the most consistent
response across species. By comparing multiple variables simultaneously, better
separation of both species and exposure was observed. The inclusion of novel
metrics can reinforce previously established concepts and provide a new
perspective. Additionally, the inclusion of various other metrics can greatly
increase the ability to identify and differentiate particular groups. By using
multivariate analyses and standard vegetation metrics, new aspects of the
vegetation response to explosive compounds can be identified.
PMID- 27483132
TI - Infectious Complications after Major Abdominal Cancer Surgery: In Search of
Improvable Risk Factors.
AB - BACKGROUND: Major resections for esophageal, gastric, hepatic, pancreatic, and
colorectal cancer continue to be associated with a high peri-operative morbidity
of up to 30%-40%. To a large extent, this morbidity is caused by infectious
complications that add up to a considerable burden to patients and hospital
costs. The objective of this large retrospective cross-sectional study was to
determine independent patient and operation-related risk factors for infectious
complications after major abdominal cancer operations to elucidate how infection
rates can be reduced and improve health-care quality. PATIENTS AND METHODS: In
1,389 cancer patients who underwent a major resection procedure between 2009 and
2013, infectious complications and their independent determinants were analyzed
by multivariable logistic regression (p < 0.05). RESULTS: Male gender was a risk
factor for infections in general, whereas patients >=65 y (odds ratio [OR] 1.75;
p = 0.008), urinary tract infection (OR 0.51; p = 0.004), American Society of
Anesthesiologists score (OR 1.55; p = 0.004), overall (OR 1.70; p = 0.037),
vascular (OR 1.59; p = 0.020), and neurologic comorbidity (OR 2.22; p = 0.001)
were associated significantly with pneumonia. Intra-abdominal drainage (OR 1.41;
p = 0.024) and a duration of surgery of >=180 min (OR 1.85; p = 0.001) were risk
factors for surgical site infections. Total parenteral nutrition was
significantly associated with intravascular catheter-induced infections (OR
18.09; p < 0.001) and sepsis (OR 6.69; p < 0.001). CONCLUSIONS: In this study,
several independent risk factors for infectious complications in major abdominal
cancer operations were identified, providing opportunities for further reducing
peri-operative infections. General awareness and focus on preventing infectious
complications may have a significant impact on health-care outcomes and costs.
PMID- 27483133
TI - Investigation of Metabolism of Exogenous Glucose at the Early Stage and Onset of
Diabetes Mellitus in Otsuka Long-Evans Tokushima Fatty Rats Using [1, 2, 3
13C]Glucose Breath Tests.
AB - This study aimed to evaluate changes in glucose metabolism at the early stage and
onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats.
Specifically, after the oral administration of [1, 2, 3-13C]glucose, the levels
of exhaled 13CO2, which most likely originated from pyruvate decarboxylation and
tricarboxylic acid, were measured. Eight OLETF rats and eight control rats (Long
Evans Tokushima Otsuka [LETO]) were administered 13C-glucose. Three types of 13C
glucose breath tests were performed thrice in each period at 2-week intervals. [3
13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule,
which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C
at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on
metabolic differences of the labeled sites, glucose metabolism was evaluated
using the results of three breath tests. The increase in 13CO2 excretion in OLETF
rats was delayed in all three breath tests compared to that in control rats,
suggesting that OLETF rats had a lower glucose metabolism than control rats. In
addition, overall glucose metabolism increased with age in both groups. The
utilization of [2-13C]glucose was suppressed in OLETF rats at 6-12 weeks of age,
but they showed higher [3-13C]glucose oxidation than control rats at 22-25 weeks
of age. In the [1-13C]glucose breath test, no significant differences in the area
under the curve until 180 minutes (AUC180) were observed between OLETF and LETO
rats of any age. Glucose metabolism kinetics were different between the age
groups and two groups of rats; however, these differences were not significant
based on the overall AUC180 of [1-13C]glucose. We conclude that breath 13CO2
excretion is reduced in OLETF rats at the primary stage of prediabetes,
indicating differences in glucose oxidation kinetics between OLETF and LETO rats.
PMID- 27483134
TI - Graphene Jet Nanomotors in Remote Controllable Self-Propulsion Swimmers in Pure
Water.
AB - A remote controllable working graphite nanostructured swimmer based on a graphene
jet nanomotor has been demonstrated for the first time. Graphite particles with
pyramidal-like morphologies were fabricated by the creation of suitable defects
in wide high-purity graphite flakes followed by a severe sonication. The
particles were able to be self-exfoliated in water after Na intercalation between
the graphene constituents. The self-exfoliation resulted in jet ejection of
graphene flakes from the end of the swimmers (with speeds as high as ~7000 m/s),
producing a driving force (at least ~0.7 L (pN) where L (MUm) is swimmer size)
and consequently the motion of the swimmer (with average speed of ~17-40 MUm/s).
The jet ejection of the graphene flakes was assigned to the explosion of H2
nanobubbles produced between the Na intercalated flakes. The direction of motion
of the swimmers equipped with TiO2 nanoparticles (NPs) can be controlled by
applying a magnetic field in the presence of UV irradiation (higher UV intensity,
lower radius of rotation). In fact, the negative surface charge of the graphene
flakes of the swimmers increased by UV irradiation due to transferring the
photoexcited electrons of TiO2 NPs into the flakes. Because of higher production
of H2 nanobubbles under UV irradiation, the speed of swimmers exposed to UV light
significantly increased. In contrast, UV irradiation with various intensities
could not affect total distance traversed by the self-exfoliated swimmers having
the same initial sizes. These confirmed the mass ejection mechanism for motion of
the swimmers. The self-exfoliation of swimmers (and so their motion) occurred
only in water (and not, e.g., in organic solutions). Such swimmers promise the
design of remote controllable nanovehicles with the capability of initiating
and/or improving their operations in response to environmental changes in order
to realize broad ranges of versatile and fantastic nanotechnology-based
applications.
PMID- 27483135
TI - Surface Molecules Released by Trypanosoma cruzi Metacyclic Forms Downregulate
Host Cell Invasion.
AB - BACKGROUND: The question whether metacylic trypomastigote (MT) forms of different
T. cruzi strains differentially release surface molecules, and how they affect
host cell invasion, remains to be fully clarified. We addressed that question
using T. cruzi strains that differ widely in the ability to invade cells.
METHODOLOGY/PRINCIPAL FINDINGS: Metacyclic forms were incubated at 37 degrees C
for 1 h in complete D10 medium or in nutrient-deprived PBS containing Ca2+ and
Mg2+ (PBS++). The conditioned medium (CM), collected after parasite
centrifugation, was used for cell invasion assays and Western blot analysis,
using monoclonal antibodies directed to gp82 and gp90, the MT surface molecules
that promote and negatively regulate invasion, respectively. CM of poorly
invasive G strain (G-CM) contained high amounts of gp90 and gp82, either in
vesicles or as soluble molecules. CM of highly invasive CL strain (CL-CM)
contained gp90 and gp82 at very low levels. HeLa cells were incubated for 1 h
with CL strain MT in D10, in absence or in the presence of G-CM or CL-CM.
Parasite invasion was significantly inhibited by G-CM, but not by CL-CM. As G
strain MT invasion rate in D10 is very low, assays with this strain were
performed in PBS++, which induces invasion-promoting lysosome-spreading. G-CM,
but not CL-CM, significantly inhibited G strain internalization, effect that was
counteracted by preincubating G-CM with an anti-gp90 monoclonal antibody or anti
gp82 polyclonal antibody that do not recognize live MT. G strain CM generated in
PBS++ contained much lower amounts of gp90 and gp82 as compared to CM produced in
D10, and exhibited lower inhibitory effect on host cell invasion.
CONCLUSION/SIGNIFICANCE: Our data suggest that the surface molecules
spontaneously released by MT impair parasite-host cell interaction, gp82
presumably competing with the molecule expressed on MT surface for the host cell
receptor, and gp90 further contributing to down modulate invasion.
PMID- 27483136
TI - South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant
Shigella sonnei: A Cross-Sectional Study.
AB - BACKGROUND: Antimicrobial resistance is a major issue in the Shigellae,
particularly as a specific multidrug-resistant (MDR) lineage of Shigella sonnei
(lineage III) is becoming globally dominant. Ciprofloxacin is a recommended
treatment for Shigella infections. However, ciprofloxacin-resistant S. sonnei are
being increasingly isolated in Asia and sporadically reported on other
continents. We hypothesized that Asia is a primary hub for the recent
international spread of ciprofloxacin-resistant S. sonnei. METHODS AND FINDINGS:
We performed whole-genome sequencing on a collection of 60 contemporaneous
ciprofloxacin-resistant S. sonnei isolated in four countries within Asia
(Vietnam, n = 11; Bhutan, n = 12; Thailand, n = 1; Cambodia, n = 1) and two
outside of Asia (Australia, n = 19; Ireland, n = 16). We reconstructed the recent
evolutionary history of these organisms and combined these data with their
geographical location of isolation. Placing these sequences into a global
phylogeny, we found that all ciprofloxacin-resistant S. sonnei formed a single
clade within a Central Asian expansion of lineage III. Furthermore, our data show
that resistance to ciprofloxacin within S. sonnei may be globally attributed to a
single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I, and
gyrA-D87G mutations. Geographical data predict that South Asia is the likely
primary source of these organisms, which are being regularly exported across Asia
and intercontinentally into Australia, the United States and Europe. Our analysis
was limited by the number of S. sonnei sequences available from diverse
geographical areas and time periods, and we cannot discount the potential
existence of other unsampled reservoir populations of antimicrobial-resistant S.
sonnei. CONCLUSIONS: This study suggests that a single clone, which is widespread
in South Asia, is likely driving the current intercontinental surge of
ciprofloxacin-resistant S. sonnei and is capable of establishing endemic
transmission in new locations. Despite being limited in geographical scope, our
work has major implications for understanding the international transfer of
antimicrobial-resistant pathogens, with S. sonnei acting as a tractable model for
studying how antimicrobial-resistant Gram-negative bacteria spread globally.
PMID- 27483137
TI - Sustaining and Expanding Telehealth: A Survey of Business Models from Selected
Prominent U.S. Telehealth Centers.
AB - INTRODUCTION: Telehealth centers across the country, including our own center,
are addressing sustainability and best practice business models. We undertook
this survey to explore the business models being used at other established
telehealth centers. In the literature on telehealth and sustainability, there is
a paucity of comparative studies as to how successful telehealth centers
function. METHODS: In this study, we compared the business models of 10
successful telehealth centers. We conducted the study by interviewing key
individuals at the centers, either through teleconference or telephone. RESULTS:
We found that there are five general approaches to sustaining a telehealth
center: grants, telehealth network membership fees, income from providing
clinical services, per encounter charges, and operating as a cost center. We also
found that most centers use more than one approach. CONCLUSION: We concluded
that, although the first four approaches can contribute to the success of a
center, telehealth centers are and should remain cost centers for their
respective institutions.
PMID- 27483139
TI - Formation of Highly Thermostable Copper-Containing Energetic Coordination
Polymers Based on Oxidized Triaminoguanidine.
AB - A series of novel highly thermostable energetic coordination polymers (ECPs),
with promising mechanical sensitivity properties, were prepared by an in situ
oxidation-coordination reaction of triaminoguanidine hydrochloride with copper
nitrate in aqueous solution. The molecular structures and properties of these
ECPs could be tuned, by varying the ratios and concentrations of the starting
materials. Our ECPs exhibit remarkable thermostability (>390 degrees C) and very
low sensitivity to impact (Im > 98 J). The best-performing material (ECP-5) has a
calculated detonation velocity of 8969 m.s(-1) and a decomposition peak
temperature of 396.9 degrees C, demonstrating an outstanding balance between two
inherently contradicting properties: high detonation performance and very low
sensitivity.
PMID- 27483138
TI - Shared Genetic Factors Involved in Celiac Disease, Type 2 Diabetes and Anorexia
Nervosa Suggest Common Molecular Pathways for Chronic Diseases.
AB - BACKGROUND AND OBJECTIVES: Genome-wide association studies (GWAS) have identified
several genetic regions involved in immune-regulatory mechanisms to be associated
with celiac disease. Previous GWAS also revealed an over-representation of genes
involved in type 2 diabetes and anorexia nervosa associated with celiac disease,
suggesting involvement of common metabolic pathways for development of these
chronic diseases. The aim of this study was to extend these previous analyses to
study the gene expression in the gut from children with active celiac disease.
MATERIAL AND METHODS: Thirty six target genes involved in type 2 diabetes and
four genes associated with anorexia nervosa were investigated for gene expression
in small intestinal biopsies from 144 children with celiac disease at median
(range) age of 7.4 years (1.6-17.8) and from 154 disease controls at a median
(range) age 11.4.years (1.4-18.3). RESULTS: A total of eleven of genes were
differently expressed in celiac patients compared with disease controls of which
CD36, CD38, FOXP1, SELL, PPARA, PPARG, AGT previously associated with type 2
diabetes and AKAP6, NTNG1 with anorexia nervosa remained significant after
correction for multiple testing. CONCLUSION: Shared genetic factors involved in
celiac disease, type 2 diabetes and anorexia nervosa suggest common underlying
molecular pathways for these diseases.
PMID- 27483140
TI - Meniscus Shape and Wetting Competition of a Drop between a Cone and a Plane.
AB - The formation of a liquid bridge between a cone and a plane is related to dip-pen
nanolithography. The meniscus shape and rupture process of a liquid meniscus
between a cone and a plane are investigated by Surface Evolver, many-body
dissipative particle dynamics, and macroscopic experiments. Dependent on the cone
geometry, cone-plane separation, and wetting properties of cone and plane, three
types of menisci can be observed before rupture and two types of wetting
competition outcomes are seen after breakup. It is interesting to find that after
rupture, the bulk of the liquid bridge volume is not necessarily retained by the
cone which is more wettable. In fact, a sharp hydrophilic cone often loses
wetting competition to a hydrophobic plane. To explain our findings, the
"apparent" contact angle of the cone is introduced and the behavior of drop-on
cone/plane system is analogous to that of a liquid bridge between two parallel
planes based on this concept.
PMID- 27483141
TI - Systematic Proteomic Identification of the Heat Shock Proteins (Hsp) that
Interact with Estrogen Receptor Alpha (ERalpha) and Biochemical Characterization
of the ERalpha-Hsp70 Interaction.
AB - Heat shock proteins (Hsps) are known to associate with estrogen receptors (ER)
and regulate ER-mediated cell proliferation. Historically, the studies in this
area have focused on Hsp90. However, some critical aspects of the Hsp-ERalpha
interactions remain unclear. For example, we do not know which Hsps are the major
or minor ERalpha interactants and whether or not different Hsp isoforms associate
equally with ERalpha. In the present study, through a quantitative proteomic
method we found that 21 Hsps and 3 Hsp cochaperones were associated with ERalpha
in human 293T cells that were cultured in a medium containing necessary elements
for cell proliferation. Four Hsp70s (Hsp70-1, Hsc70, Grp75, and Grp78) were the
most abundant Hsps identified to associate with ERalpha, followed by two Hsp90s
(Hsp90alpha and Hsp90beta) and three Hsp110s (Hsp105, HspA4, and HspA4L).
Hsp90alpha was found to be 2-3 times more abundant than Hsp90beta in the ERalpha
containing complexes. Among the reported Hsp cochaperones, we detected
prostaglandin E synthase 3 (p23), peptidyl-prolyl cis-trans isomerase FKBP5
(FKBP51), and E3 ubiquitin-protein ligase CHIP (CHIP). Studies with the two most
abundant ERalpha-associated Hsps, Hsp70-1 and Hsc70, using human breast cancer
MCF7 cells demonstrate that the two Hsps interacted with ERalpha in both the
cytoplasm and nucleus when the cells were cultured in a medium supplemented with
fetal bovine serum and phenol red. Interestingly, the ERalpha-Hsp70-1/Hsc70
interactions were detected only in the cytoplasm but not in the nucleus under
hormone starvation conditions, and stimulation of the starved cells with 17beta
estradiol (E2) did not change this. In addition, E2-treatment weakened the
ERalpha-Hsc70 interaction but had no effect on the ERalpha-Hsp70-1 interaction.
Further studies showed that significant portions of Hsp70-1 and Hsc70 were
associated with transcriptionally active chromatin and inactive chromatin, and
the two Hsps interacted with ERalpha in both forms of the chromatins in MCF7
cells.
PMID- 27483142
TI - Asymmetric Regulation of Peripheral Genes by Two Transcriptional Regulatory
Networks.
AB - Transcriptional regulatory network (TRN) reconstitution and deconstruction occur
simultaneously during reprogramming; however, it remains unclear how the starting
and targeting TRNs regulate the induction and suppression of peripheral genes.
Here we analyzed the regulation using direct cell reprogramming from human dermal
fibroblasts to monocytes as the platform. We simultaneously deconstructed
fibroblastic TRN and reconstituted monocytic TRN; monocytic and fibroblastic gene
expression were analyzed in comparison with that of fibroblastic TRN
deconstruction only or monocytic TRN reconstitution only. Global gene expression
analysis showed cross-regulation of TRNs. Detailed analysis revealed that
knocking down fibroblastic TRN positively affected half of the upregulated
monocytic genes, indicating that intrinsic fibroblastic TRN interfered with the
expression of induced genes. In contrast, reconstitution of monocytic TRN showed
neutral effects on the majority of fibroblastic gene downregulation. This study
provides an explicit example that demonstrates how two networks together regulate
gene expression during cell reprogramming processes and contributes to the
elaborate exploration of TRNs.
PMID- 27483156
TI - Art in the Digital Age
AB - The genre of "computer art" began in the 1950s, when long exposure photography
was used to capture images created by an oscilloscope manipulating electronic
waves on a small fluorescent screen. Through the 1960s, most works of computer
art were created using plotters and impact printers by the scientists and
engineers who had access to emerging computing technology. By the 1970s, artists
were learning to program, and some universities began to integrate computers into
the fine arts curriculum. The widespread adoption of computers and the
availability of off-the-shelf paint programs in the 1980s brought computer art to
the masses. At the same time, computer graphics and special effects were
beginning their takeover of the entertainment industry through Hollywood films,
TV shows, and video games. By the 1990s, the term computer art was fading, and
computers were becoming a mainstream part of arts and entertainment.
PMID- 27483159
TI - The Application of Magnetic Bead Selection to Investigate Interactions between
the Oral Microbiota and Salivary Immunoglobulins.
AB - The effect of humoral immunity on the composition of the oral microbiota is less
intensively investigated than hygiene and diet, in part due to a lack of simple
and robust systems for investigating interactions between salivary
immunoglobulins and oral bacteria. Here we report the application of an ex situ
method to investigate the specificity of salivary immunoglobulins for salivary
bacteria. Saliva collected from six volunteers was separated into immunoglobulin
and microbial fractions, and the microbial fractions were then directly exposed
to salivary immunoglobulins of "self" and "non-self" origin. Antibody-selected
bacteria were separated from their congeners using a magnetic bead system,
selective for IgA or IgG isotypes. The positively selected fractions were then
characterized using gel-based eubacterial-specific DNA profiling. The eubacterial
profiles of positively selected fractions diverged significantly from profiles of
whole salivary consortia based on volunteer (P<= 0.001%) and immunoglobulin
origin (P<= 0.001%), but not immunoglobulin isotype (P = 0.2). DNA profiles of
separated microbial fractions were significantly (p<= 0.05) less diverse than
whole salivary consortia and included oral and environmental bacteria. Consortia
selected using self immunoglobulins were generally less diverse than those
selected with immunoglobulins of non-self origin. Magnetic bead separation
facilitated the testing of interactions between salivary antibodies and oral
bacteria, showing that these interactions are specific and may reflect
differences in recognition by self and non-self immunoglobulins. Further
development of this system could improve understanding of the relationship
between the oral microbiota and the host immune system and of mechanisms
underlying the compositional stability of the oral microbiota.
PMID- 27483161
TI - Cationic Ionic Liquids Organic Ligands Based Metal-Organic Frameworks for
Fabrication of Core-Shell Microspheres for Hydrophilic Interaction Liquid
Chromatography.
AB - In this study, new metal-organic frameworks (MOFs) nanocrystals modified SiO2
core-shell microspheres were designed with cationic ionic liquids (ILs) 1,3-bis(4
carboxybutyl)imidazolium bromide (ILI) as organic ligands. By further adjustment
the growth cycles, the new ILI-01@SiO2 core-shell stationary phase was facilely
fabricated. The developed stationary phase was respectively characterized via
element analysis, thermogravimetric analysis, scanning electron microscopy, X-ray
diffraction, and Fourier transform infrared spectrometry. Because the
introduction of cationic imidazolium-based ILs ILI for fabrication of the MOFs
nanocrystals shell, the new stationary phase exhibits the retention mechanism of
hydrophilic interaction liquid chromatography (HILIC). Many polar samples, such
as amides, vitamins, nucleic acid bases, and nucleosides, were utilized to
investigate the performance of the prepared ILI-01@SiO2 column. Compared to the
conventional aminosilica column, the new ILI-01@SiO2 column displays high
separation selectivity in a shorter separation time. Furthermore, the new ILI
01@SiO2 column was also used for detection of illegal melamine addition in the
baby formula. All the above results demonstrate the new ILI-01@SiO2 core-shell
stationary phase is of good potentials for high-selectivity separation the polar
samples.
PMID- 27483160
TI - The Yield of Community-Based "Retrospective" Tuberculosis Contact Investigation
in a High Burden Setting in Ethiopia.
AB - OBJECTIVE: To determine the yield and determinants of retrospective TB contact
investigation in selected zones in Ethiopia. MATERIALS AND METHODS: This was a
community-based cross-sectional study conducted during June-October 2014.Trained
lay providers performed symptom screening for close contacts of index cases with
all types of TB registered for anti-TB treatment within the last three years. We
used logistic regression to determine factors associated with TB diagnosis among
the contacts. RESULTS: Of 272,441 close contacts of 47, 021 index cases screened,
13,886 and 2, 091 had presumptive and active TB respectively. The yield of active
TB was thus 768/100, 000, contributing 25.4% of the 7,954 TB cases reported from
the study zones over the study period. The yield was highest among workplace
contacts (12,650/100, 000). Active TB was twice more likely among contacts whose
index cases had been registered for TB treatment within the last 12 months
compared with those who had been registered 24 or more months earlier (adjusted
odds ratio, AOR: 1.77 95% CI 1.42-2.21). Sex or clinical type of TB in index
cases was not associated with the yield. Smear negative (SS-) index cases (AOR:
1.74 955 CI 1.13-2.68), having index cases who registered for treatment within
<12 months (AOR: 2.41 95% CI 1.51-3.84) and being household contact (AOR: 0.072
95% CI 0.01-0.52) were associated with the occurrence of active TB in children.
CONCLUSIONS: The yield of retrospective contact investigation was about six times
the case notification in the study zones, contributing a fourth of all TB cases
notified over the same period. The yield was highest among workplace contacts and
in those with recent past history of contact. Retrospective contact screening can
serve as additional strategy to identify high risk groups not addressed through
currently recommended screening approaches.
PMID- 27483162
TI - The PE_PGRS Proteins of Mycobacterium tuberculosis Are Ca(2+) Binding Mediators
of Host-Pathogen Interaction.
AB - The phenomenal success of Mycobacterium tuberculosis (M.tb) as a pathogen is
primarily based on its ability to modulate host immune responses. The genome of
M.tb encodes multiple immunomodulatory proteins, including several members of the
multigenic PE_PPE family of which the PE_PGRS proteins are a subset. Curiously,
56 of the 61 PE_PGRS proteins contain multiple copies of the glycine-rich
sequence motif GGXGXD/NXUX, a nonapeptide sequence predicted to bind Ca(2+), but
the functional significance of these motifs remains a mystery. Here we provide
evidence via isothermal titration calorimetry, (45)Ca blotting, fluorescence, and
circular dichroism spectroscopy that Ca(2+) binds to the PE_PGRS proteins,
PE_PGRS33 (Rv1818c) (10 motifs) and PE_PGRS61 (Rv3653) (one motif). Ca(2+) was
observed not to bind to PE_PGRS8 (Rv0742), which lacks nonapeptide motifs. Using
recombinant Mycobacterium smegmatis strains expressing Rv1818c and Rv3653 and the
THP-1 macrophage model of infection, we show that the two proteins mediate Ca(2+)
dependent upregulation of the anti-inflammatory cytokine IL-10, events critical
to the pathogenesis of M.tb. Both Rv1818c and Rv3653 interact with TLR2 in a
Ca(2+)-dependent manner, providing a novel mechanistic basis for their
immunomodulatory effects. Mutations in the nonapeptide motif of Rv3653 led to
compromised Ca(2+) binding, validating the functional criticality of this motif.
This study demonstrates for the first time not only their Ca(2+) binding
properties but also an essential role for Ca(2+) in the functioning of the M.tb
PE_PGRS proteins, opening up the possibility of developing novel anti
tuberculosis therapeutics that inhibit Ca(2+)-PE_PGRS binding.
PMID- 27483164
TI - "The Golden Method": Electrochemical Synthesis Is an Efficient Route to Gold
Complexes.
AB - Gold compounds to be obtained by the direct electrochemical oxidation of a noble
metal are reported. This achievement provides an alternative procedure to
obtaining neutral gold compounds with potential medical or catalytic
applications.
PMID- 27483163
TI - Aminophylline Dosage In Asthma Exacerbations in Children: A Systematic Review.
AB - BACKGROUND: Adequate asthma treatment of childhood exacerbations with IV
aminophylline depends on appropriate dosage. Recommendations to aim for a target
therapeutic range may be inappropriate as serum concentrations correlate poorly
with clinical improvement. This review aims to evaluate the evidence for the
optimum dosage strategy of intravenous aminophylline in children suffering an
exacerbation of asthma. METHODS: A systematic review comparing dosage regimens of
intravenous aminophylline in children suffering an exacerbation of asthma.
Primary outcomes were time until resolution of symptoms, mortality and need for
mechanical ventilation. Secondary outcomes were date until discharge criteria are
met, actual discharge and adverse effects. DATA SOURCES: CENTRAL, CINAHL, MEDLINE
and Web of Science. Search performed in March 2016. ELIGIBILITY CRITERIA: Studies
using intravenous aminophylline in children with an acute exacerbation of asthma
which reported the dosage and clinical outcomes. FINDINGS: 14 RCTs were included.
There is a poor relationship between the dosage administered to children and
symptom resolution, length of stay or need for mechanical ventilation. This study
is limited due to its use of indirect evidence. CONCLUSION: The currently
recommended dosage regimens may not represent the optimum safety and efficacy of
intravenous aminophylline. There is a need to develop the evidence base
correlating dosage with patient centered clinical outcomes, to improve
prescribing practices.
PMID- 27483165
TI - Facile Synthesis of Sub-20 nm Silver Nanowires through a Bromide-Mediated Polyol
Method.
AB - Essentially all of the Ag nanowires reported in the literature have sizes larger
than 30 nm in diameter. In this article, we report a simple and robust approach
to the synthesis of Ag nanowires with diameters below 20 nm and aspect ratios
over 1000 using a one-pot polyol method. The Ag nanowires took a penta-twinned
structure, and they could be obtained rapidly (<35 min) and in high morphology
purity (>85% of the as-obtained solid product) under atmospheric pressure. The
key to the success of this synthesis is to restrain the nanowires from lateral
growth by employing both Br(-) ions and poly(vinylpyrrolidone) with a high
molecular weight of 1 300 000 g/mol to cap the {100} side faces, together with
the use of a syringe pump to slowly introduce AgNO3 into the reaction solution.
By optimizing the ratios between the capping agents and AgNO3, we were able to
slow down the reduction kinetics and effectively direct the Ag nanowires to grow
along the longitudinal direction only. The nanowires showed great mechanical
flexibility and could be bent with acute angles without breaking. Because of
their small diameters, the transverse localized surface plasmon resonance peak of
the Ag nanowires could be pushed down to the ultraviolet region, below 400 nm,
making them ideal conductive elements for the fabrication of touch screens, solar
cells, and smart windows.
PMID- 27483166
TI - Total Focusing Method With Virtual Sources in the Presence of Unknown Geometry
Interfaces.
AB - Auto-focused virtual source imaging (AVSI) has been recently presented as an
alternative method for synthetic aperture focusing through arbitrarily shaped
interfaces with arrays. This paper extends the AVSI concept to the case of the
total focusing method (TFM-AVSI) using several virtual receivers for each virtual
source. This approach overcomes the known contrast limitation of AVSI, while
preserving the advantage of performing synthetic focusing in the second medium
only [no time-of-flight (TOF) calculations through the interface]. In contrast,
equipment with more active channels must be used to digitalize the signals
received by all the array elements after each focused emission. When compared
with the conventional TFM, the proposed method reduces the processing complexity
of the most time consuming task: TOF calculation in the presence of interfaces.
This improvement could lead to more efficient real-time implementations of the
TFM in non-destructive testing applications where water immersion or flexible
wedges are used. In this paper, the mathematical formulation for the new method
is given, accounting for the surface slope and the array angular sensitivity. Its
performance is evaluated by numerical simulation, experimentally and compared
with AVSI and the conventional TFM. It was found that the TFM-AVSI achieves the
same resolution and contrast as that of the TFM, although it shows a wider blind
zone below the interface due to focusing with normal incidence.
PMID- 27483171
TI - Thermodynamic Hydricity of Transition Metal Hydrides.
AB - Transition metal hydrides play a critical role in stoichiometric and catalytic
transformations. Knowledge of free energies for cleaving metal hydride bonds
enables the prediction of chemical reactivity, such as for the bond-forming and
bond-breaking events that occur in a catalytic reaction. Thermodynamic hydricity
is the free energy required to cleave an M-H bond to generate a hydride ion (H(
)). Three primary methods have been developed for hydricity determination: the
hydride transfer method establishes hydride transfer equilibrium with a hydride
donor/acceptor pair of known hydricity, the H2 heterolysis method involves
measuring the equilibrium of heterolytic cleavage of H2 in the presence of a
base, and the potential-pKa method considers stepwise transfer of a proton and
two electrons to give a net hydride transfer. Using these methods, over 100
thermodynamic hydricity values for transition metal hydrides have been determined
in acetonitrile or water. In acetonitrile, the hydricity of metal hydrides spans
a range of more than 50 kcal/mol. Methods for using hydricity values to predict
chemical reactivity are also discussed, including organic transformations, the
reduction of CO2, and the production and oxidation of hydrogen.
PMID- 27483170
TI - De Novo Assembly and Comparative Transcriptome Analyses of Red and Green Morphs
of Sweet Basil Grown in Full Sunlight.
AB - Sweet basil (Ocimum basilicum), one of the most popular cultivated herbs
worldwide, displays a number of varieties differing in several characteristics,
such as the color of the leaves. The development of a reference transcriptome for
sweet basil, and the analysis of differentially expressed genes in acyanic and
cyanic cultivars exposed to natural sunlight irradiance, has interest from
horticultural and biological point of views. There is still great uncertainty
about the significance of anthocyanins in photoprotection, and how green and red
morphs may perform when exposed to photo-inhibitory light, a condition plants
face on daily and seasonal basis. We sequenced the leaf transcriptome of the
green-leaved Tigullio (TIG) and the purple-leaved Red Rubin (RR) exposed to full
sunlight over a four-week experimental period. We assembled and annotated 111,007
transcripts. A total of 5,468 and 5,969 potential SSRs were identified in TIG and
RR, respectively, out of which 66 were polymorphic in silico. Comparative
analysis of the two transcriptomes showed 2,372 differentially expressed genes
(DEGs) clustered in 222 enriched Gene ontology terms. Green and red basil mostly
differed for transcripts abundance of genes involved in secondary metabolism.
While the biosynthesis of waxes was up-regulated in red basil, the biosynthesis
of flavonols and carotenoids was up-regulated in green basil. Data from our study
provides a comprehensive transcriptome survey, gene sequence resources and
microsatellites that can be used for further investigations in sweet basil. The
analysis of DEGs and their functional classification also offers new insights on
the functional role of anthocyanins in photoprotection.
PMID- 27483172
TI - Correction: Prooxidative Potential of Photo-Irradiated Aqueous Extracts of Grape
Pomace, a Recyclable Resource from Winemaking Process.
AB - [This corrects the article DOI: 10.1371/journal.pone.0158197.].
PMID- 27483175
TI - Atypical presentation of posterior reversible encephalopathy syndrome: Clinical
and radiological characteristics in eclamptic patients.
AB - Posterior reversible encephalopathy syndrome (PRES) is an obstetric emergency
frequently occurring in a pregnant or puerperal woman, manifested with an acute
headache, consciousness impairment, seizures, and visual deficits and is
associated with white matter changes predominantly affecting the posterior
parietal and occipital lobes of the brain. Apart from the above-described typical
location of the changes, the most common atypical location involves the brain
stem and basal ganglia. Since magnetic resonance imaging (MRI) is more sensitive
and specific imaging technique compared to computerized tomography, establishing
the diagnosis and follow-up in patients with PRES is based mainly on MRI
findings. It is particularly important not to exclude PRES as a possible
diagnosis when we have the appropriate clinical presentation accompanied by the
atypical radiological findings, since this clinical-radiological syndrome can
often be manifested with an atypical MRI image.
PMID- 27483173
TI - MTHFR and ACE Polymorphisms Do Not Increase Susceptibility to Migraine Neither
Alone Nor in Combination.
AB - OBJECTIVE: The aim of this study was to confirm previous reports in order to
substantiate the hypothesis that functional variants of two genes, namely
methylenetetrahydrofolate reductase and angiotensin I converting enzyme, both
involved in an important pathway of migraine, increase migraine susceptibility
when present in combination. BACKGROUND: Migraine is a complex genetic disease.
The migraine attack is thought to be the result of an interaction of neuronal and
vascular events, possibly originating in the brainstem leading to activation of
the pain processing trigeminovascular system. Functional variants in the
methylenetetrahydrofolate gene and the angiotensin I converting enzyme have
influence on vascular mechanism and have been investigated intensively in
migraine. The published results were inconsistent; however, both polymorphisms in
combination have been shown to increase migraine susceptibility. METHODS: In this
genetic association study, the prevalence of the functionally relevant
polymorphisms C677T in the MTHFR gene and I/D polymorphism in the ACE gene was
compared in 420 patients with migraine vs 258 migraine-free controls using a chi
square statistic and binary logistic regression. RESULTS: Susceptibility to any
type of migraine (migraine with aura, migraine without aura, and both types
combined) was neither increased by each polymorphism on its own, nor in
combination (MTHFR: X(2) = 0.18 [P = .91]; ACE: X(2) = 1.62 [P = .45];
combined: OR = 1.02 [95% CI 0.98-1.05] P = .97). CONCLUSIONS: We could not
replicate a previous study that showed significant increase in migraine
susceptibility for two functional polymorphisms in genes affecting relevant
pathways.
PMID- 27483180
TI - Missense splice variant (g.20746A>G, p.Ile183Val) of interferon gamma receptor 1
(IFNGR1) coincidental with mycobacterial osteomyelitis - a screen of
osteoarticular lesions.
AB - Previously, dominant partial interferon-gamma receptor 1 (IFN-g-R1)
susceptibility to environmental mycobacteria was found with IFNGR1 deletions or
premature stop. Our aim was to search for IFNGR1 variants in patients with
mycobacterial osteoarticular lesions. Biopsies from the patients were examined
for acid-fast bacilli, inflammatory cell infiltration, and mycobacterial niacin.
Mycobacterial rRNA was analyzed using a target-amplified rRNA probe test.
Peripheral-blood-leukocyte genomic DNA was isolated from 19 patients using the
QIAamp DNA Mini Kit, and all IFNGR1 exons were sequenced using an ABIPRISM 3130
device. After the discovery of an exon 5 variant, a Polish newborn population
sample (n = 100) was assayed for the discovered variant. Splice sites and
putative amino acid interactions were analyzed. All patients tested were positive
for mycobacteria; one was heterozygous for the IFNGR1 exon 5 single-nucleotide
missense substitution (g.20746A>G, p.Ile183Val). No other variant was found. The
splice analysis indicated the creation of an exonic splicing silencer, and
alternatively, molecular graphics indicated that the p.Ile183Val might alter beta
strand packing (loss of van der Waals contacts; Val183/Pro205), possibly altering
the IFN-g-R1/IFN-g-R2 interaction. The probability of non-deleterious variant was
estimated as <10%. Heterozygous IFNGR1:p.Ile183Val (frequency 0.003%) was found
to be coincidental with mycobacterial osteomyelitis. The small amount of
variation detected in the patients with osteoarticular lesions indicates that
screens should not yet be restricted: Intronic variants should be analyzed as
well as the other genes affecting Type 1 T-helper-cell-mediated immunity.
PMID- 27483185
TI - Can text messages increase safer sex behaviours in young people? Intervention
development and pilot randomised controlled trial.
AB - BACKGROUND: Younger people bear the heaviest burden of sexually transmitted
infections (STIs). Partner notification, condom use and STI testing can reduce
infection but many young people lack the knowledge, skills and confidence needed
to carry out these behaviours. Text messages can provide effective behavioural
support. The acceptability and feasibility of a randomised controlled trial of
safer sex support delivered by text message are not known. OBJECTIVES: To assess
the acceptability and feasibility of a randomised controlled trial of a safer sex
intervention delivered by text message for young people aged 16-24 years. DESIGN:
(1) Intervention development; (2) follow-up procedure development; (3) a pilot,
parallel-arm randomised controlled trial with allocation via remote automated
randomisation (ratio of 1 : 1) (participants were unmasked, whereas researchers
analysing samples and data were masked); and (4) qualitative interviews. SETTING:
Participants were recruited from sexual health services in the UK. PARTICIPANTS:
Young people aged 16-24 years diagnosed with chlamydia or reporting unprotected
sex with more than one partner in the last year. INTERVENTIONS: A theory- and
evidence-based safer sex intervention designed, with young people's input, to
reduce the incidence of STIs by increasing the correct treatment of STIs, partner
notification, condom use and STI testing before unprotected sex with a new
partner. The intervention was delivered via automated mobile phone messaging over
12 months. The comparator was a monthly text message checking contact details.
MAIN OUTCOME MEASURES: (1) Development of the intervention based on theory,
evidence and expert and user views; (2) follow-up procedures; (3) pilot trial
primary outcomes: full recruitment within 3 months and follow-up rate for the
proposed primary outcomes for the main trial; and (4) participants' views and
experiences regarding the acceptability of the intervention. RESULTS: In total,
200 participants were randomised in the pilot trial, of whom 99 were allocated to
the intervention and 101 were allocated to the control. We fully recruited early
and achieved an 81% follow-up rate for our proposed primary outcome of the
cumulative incidence of chlamydia at 12 months. There was no differential follow
up between groups. In total, 97% of messages sent were successfully delivered to
participants' mobile phones. Recipients reported that the tone, language, content
and frequency of messages were appropriate. Messages reportedly increased
knowledge of and confidence in how to use condoms and negotiate condom use and
reduced stigma about STIs, enabling participants to tell a partner about a STI.
CONCLUSIONS: Our research shows that the intervention is acceptable and feasible
to deliver. Our pilot trial demonstrated that a main trial is feasible. It
remains unclear which behaviour change techniques and elements of the
intervention or follow-up procedures are associated with effectiveness. A further
limitation is that in the trial one person entering data and the participants
were unmasked. A randomised controlled trial to establish the effects of the
intervention on STIs at 12 months is needed. TRIAL REGISTRATION: Current
Controlled Trials ISRCTN02304709. 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. 20,
No. 57. See the NIHR Journals Library website for further project information.
PMID- 27483186
TI - Identification of Covalent Binding Sites Targeting Cysteines Based on
Computational Approaches.
AB - Covalent drugs have attracted increasing attention in recent years due to good
inhibitory activity and selectivity. Targeting noncatalytic cysteines with
irreversible inhibitors is a powerful approach for enhancing pharmacological
potency and selectivity because cysteines can form covalent bonds with inhibitors
through their nucleophilic thiol groups. However, most human kinases have
multiple noncatalytic cysteines within the active site; to accurately predict
which cysteine is most likely to form covalent bonds is of great importance but
remains a challenge when designing irreversible inhibitors. In this work, FTMap
was first applied to check its ability in predicting covalent binding site
defined as the region where covalent bonds are formed between cysteines and
irreversible inhibitors. Results show that it has excellent performance in
detecting the hot spots within the binding pocket, and its hydrogen bond
interaction frequency analysis could give us some interesting instructions for
identification of covalent binding cysteines. Furthermore, we proposed a simple
but useful covalent fragment probing approach and showed that it successfully
predicted the covalent binding site of seven targets. By adopting a distance
based method, we observed that the closer the nucleophiles of covalent warheads
are to the thiol group of a cysteine, the higher the possibility that a cysteine
is prone to form a covalent bond. We believe that the combination of FTMap and
our distance-based covalent fragment probing method can become a useful tool in
detecting the covalent binding site of these targets.
PMID- 27483188
TI - Metabolomics to Detect Response of Lettuce (Lactuca sativa) to Cu(OH)2
Nanopesticides: Oxidative Stress Response and Detoxification Mechanisms.
AB - There has been an increasing influx of nanopesticides into agriculture in recent
years. Understanding the interaction between nanopesticides and edible plants is
crucial in evaluating the potential impact of nanotechnology on the environment
and agriculture. Here we exposed lettuce plants to Cu(OH)2 nanopesticides (1050
2100 mg/L) through foliar spray for one month. Inductively coupled plasma-mass
spectrometry (ICP-MS) results indicate that 97-99% (1353-2501 mg/kg) of copper
was sequestered in the leaves and only a small percentage (1-3%) (17.5-56.9
mg/kg) was translocated to root tissues through phloem loading. Gas
chromatography-time-of-flight mass spectrometry (GC-TOF-MS) based metabolomics
combined with partial least squares-discriminant analysis (PLS-DA) multivariate
analysis revealed that Cu(OH)2 nanopesticides altered metabolite levels of
lettuce leaves. Tricarboxylic (TCA) cycle and a number of amino acid-related
biological pathways were disturbed. Some antioxidant levels (cis-caffeic acid,
chlorogenic acid, 3,4-dihydroxycinnamic acid, dehydroascorbic acid) were
significantly decreased compared to the control, indicating that oxidative stress
and a defense response occurred. Nicotianamine, a copper chelator, increased by
12-27 fold compared to the control, which may represent a detoxification
mechanism. The up-regulation of polyamines (spermidine and putrescine) and
potassium may mitigate oxidative stress and enhance tolerance. The data presented
here provide a molecular-scale perspective on the response of plants to copper
nanopesticides.
PMID- 27483187
TI - Increased activity in frontal motor cortex compensates impaired speech perception
in older adults.
AB - Understanding speech in noisy environments is challenging, especially for
seniors. Although evidence suggests that older adults increasingly recruit
prefrontal cortices to offset reduced periphery and central auditory processing,
the brain mechanisms underlying such compensation remain elusive. Here we show
that relative to young adults, older adults show higher activation of frontal
speech motor areas as measured by functional MRI during a syllable identification
task at varying signal-to-noise ratios. This increased activity correlates with
improved speech discrimination performance in older adults. Multivoxel pattern
classification reveals that despite an overall phoneme dedifferentiation, older
adults show greater specificity of phoneme representations in frontal
articulatory regions than auditory regions. Moreover, older adults with stronger
frontal activity have higher phoneme specificity in frontal and auditory regions.
Thus, preserved phoneme specificity and upregulation of activity in speech motor
regions provide a means of compensation in older adults for decoding impoverished
speech representations in adverse listening conditions.
PMID- 27483189
TI - An aminopyrimidine-functionalized cage-based metal-organic framework exhibiting
highly selective adsorption of C2H2 and CO2 over CH4.
AB - There has been considerable interest in adsorptive separation of C2H2/CH4 and
CO2/CH4 gas mixtures due to its industrial significance and scientific challenge.
In this work, we have designed and synthesized a bent diisophthalate ligand
functionalized with aminopyrimidine groups, and constructed via a solvothermal
reaction, a porous copper-based framework. Single-crystal X-ray diffraction
studies show that the framework is a three-dimensional network containing three
different types of polyhedral nanocages, which are stacked together to form two
distinct types of one-dimensional channels along the crystallographic c axis. The
compound after activation shows exceptionally high C2H2 and CO2 uptakes of 211
and 120 cm(3) (STP) g(-1) at 295 K and 1 atm, as well as impressive adsorption
selectivities towards C2H2 and CO2 over CH4. High C2H2 and CO2 uptake capacities
as well as significant adsorption selectivities of C2H2 and CO2 over CH4 imply
potential applications in the adsorptive separation and purification of C2H2/CH4
and CO2/CH4 gas mixtures, which have been verified by column breakthrough
experiments. Several important binding sites for C2H2 and CO2 in ZJNU-54 were
revealed by quantum chemical calculations, demonstrating that the organic linkers
in ZJNU-54 form unique structures that facilitate the adsorption of C2H2, while
the amine groups and the Lewis basic pyrimidine-ring nitrogen sites in the
organic linker improve the adsorption energies for CO2, finally leading to the
increase of adsorption capacities for these two gas molecules. This work provides
an efficient strategy for incorporating specific functional groups into cage
based MOFs for generating new adsorbents for highly selective gas storage and
separation.
PMID- 27483192
TI - Photoisomerization of beta-Ionone Protonated Schiff Base in the Gas Phase.
AB - The photoisomerization of beta-ionone protonated Schiff base (BIPSB) is
investigated in the gas phase by irradiating mobility-selected ions in a tandem
ion mobility spectrometer with tunable radiation. Four distinguishable isomers
are produced by electrospray ionization whose structures are deduced from their
collision cross sections and photoisomerization behavior along with density
functional theory calculations. They include two geometric isomers of BIPSB with
trans or cis configurations about the polyene chain's terminal C?N double bond, a
bicyclic structure formed through electrocyclization of the polyene chain, and a
Z-retro-gamma-ionone isomer. Although trans-BIPSB and 9-cis-BIPSB have similar
photoisomerization action spectra, with a maximum response at 375 nm, they
photoconvert to different isomers. The trans-BIPSB isomer transforms to the
bicyclic form upon exposure to light over the 320-400 nm range, whereas the cis
BIPSB isomer is prevented by steric hindrance from forming the bicyclic BIPSB
isomer following irradiation and is proposed instead to form the 7,9-di-cis
isomer. Neither the bicyclic isomer nor the Z-retro-gamma-ionone isomer respond
strongly to near-UV light.
PMID- 27483190
TI - Side-Chain Conformational Preferences Govern Protein-Protein Interactions.
AB - Protein secondary structures serve as geometrically constrained scaffolds for the
display of key interacting residues at protein interfaces. Given the critical
role of secondary structures in protein folding and the dependence of folding
propensities on backbone dihedrals, secondary structure is expected to influence
the identity of residues that are important for complex formation. Counter to
this expectation, we find that a narrow set of residues dominates the binding
energy in protein-protein complexes independent of backbone conformation. This
finding suggests that the binding epitope may instead be substantially influenced
by the side-chain conformations adopted. We analyzed side-chain conformational
preferences in residues that contribute significantly to binding. This analysis
suggests that preferred rotamers contribute directly to specificity in protein
complex formation and provides guidelines for peptidomimetic inhibitor design.
PMID- 27483193
TI - Atomically Thin MoS2 Narrowband and Broadband Light Superabsorbers.
AB - We present a combined theoretical and experimental effort to enable strong light
absorption (>70%) in atomically thin MoS2 films (<=4 layers) for either
narrowband incidence with arbitrarily prespecified wavelengths or broadband
incidence like solar radiation. This is achieved by integrating the films with
resonant photonic structures that are deterministically designed using a unique
reverse design approach based on leaky mode coupling. The design starts with
identifying the properties of leaky modes necessary for the targeted strong
absorption, followed by searching for the geometrical features of nanostructures
to support the desired modes. This process is very intuitive and only involves a
minimal amount of computation, thanks to the straightforward correlations between
optical functionality and leaky modes as well as between leaky modes and the
geometrical feature of nanostructures. The result may provide useful guidance for
the development of high-performance atomic-scale photonic devices, such as solar
cells, modulators, photodetectors, and photocatalysts.
PMID- 27483194
TI - The Role of the Hydrogen Source on the Selective Production of gamma
Valerolactone and 2-Methyltetrahydrofuran from Levulinic Acid.
AB - A mechanistic study of the hydrogenation reaction of levulinic acid (LA) to 2
methyltetrahydrofuyran (MTHF) was performed using three different solvents under
reactive H2 and inert N2 atmospheres. Under the applied reaction conditions,
catalytic transfer hydrogenation and hydrogenation with molecular H2 were
effective at producing high yields of gamma-valerolactone. However, the
conversion of this stable intermediate to MTHF required the combination of both
hydrogen sources (the solvent and the H2 atmosphere) to achieve good yields. The
reaction system with 2-propanol as solvent and Ni-Cu/Al2 O3 as catalyst allowed
full conversion of LA and a MTHF yield of 80 % after 20 h reaction time at 250
degrees C and 40 bar of H2 (at room temperature). The system showed the same
catalytic activity at LA feed concentrations of 5 and up to 30 wt%, and also when
high acetone concentration at the beginning of the reaction were added, which
confirmed the potential industrial applications of this solvent/catalyst system.
PMID- 27483195
TI - pKa at Quartz/Electrolyte Interfaces.
AB - Acidity of silanol sites at the crystalline quartz/aqueous electrolyte (NaCl,
NaI, KCl) interfaces are calculated from ab initio molecular dynamics
simulations. pKa's are found to follow a combination of the cationic and anionic
Hofmeister series in the order pKa(neat solution) < pKa(NaCl) < pKa(NaI) <
pKa(KCl), in agreement with experimental measurements. Rationalization of this
ranking is achieved in terms of the microscopic local solvation of the protonated
silanols and their conjugated bases, the silanolates SiO(-). The change in the
pKa is the result of both water destructuring by alkali halides, as well as of
the specific cation/SiO(-) interaction, depending on the electrolyte. Molecular
modeling at the atomistic level is required to achieve such comprehension, with
ab initio molecular dynamics being able to model complex inhomogeneous charged
interfaces and the associated interfacial chemical reactivity.
PMID- 27483196
TI - Differential influences of local subpopulations on regional diversity and
differentiation for greater sage-grouse (Centrocercus urophasianus).
AB - The distribution of spatial genetic variation across a region can shape
evolutionary dynamics and impact population persistence. Local population
dynamics and among-population dispersal rates are strong drivers of this spatial
genetic variation, yet for many species we lack a clear understanding of how
these population processes interact in space to shape within-species genetic
variation. Here, we used extensive genetic and demographic data from 10
subpopulations of greater sage-grouse to parameterize a simulated approximate
Bayesian computation (ABC) model and (i) test for regional differences in
population density and dispersal rates for greater sage-grouse subpopulations in
Wyoming, and (ii) quantify how these differences impact subpopulation regional
influence on genetic variation. We found a close match between observed and
simulated data under our parameterized model and strong variation in density and
dispersal rates across Wyoming. Sensitivity analyses suggested that changes in
dispersal (via landscape resistance) had a greater influence on regional
differentiation, whereas changes in density had a greater influence on mean
diversity across all subpopulations. Local subpopulations, however, varied in
their regional influence on genetic variation. Decreases in the size and
dispersal rates of central populations with low overall and net immigration (i.e.
population sources) had the greatest negative impact on genetic variation.
Overall, our results provide insight into the interactions among demography,
dispersal and genetic variation and highlight the potential of ABC to disentangle
the complexity of regional population dynamics and project the genetic impact of
changing conditions.
PMID- 27483197
TI - A Sequential Method to Prepare Polymorphs and Solvatomorphs of [Fe(1,3-bpp)2
](ClO4 )2 ?nH2 O (n=0, 1, 2) with Varying Spin-Crossover Behaviour.
AB - Two polymorphs of the spin crossover (SCO) compound [Fe(1,3-bpp)2 ](ClO4 )2 (1
and 2; 1,3-bpp=2-(pyrazol-1-yl)-6-(pyrazol-3-yl)pyridine) were prepared using a
novel, stepwise procedure. Crystals of 1 deposit from dry solvents, while 2 is
obtained from a solid-state procedure, by sequentially removing lattice H2 O
molecules from the solvatomorph [Fe(1,3-bpp)2 ](ClO4 )2 ?2 H2 O (2?2 H2 O), using
single-crystal-to-single-crystal (SCSC) transformations. Hydrate 2?2 H2 O is
obtained through the same reaction as 1, now with 2.5 % of water added. Compounds
2 and 2?2 H2 O are unstable in the atmosphere and absorb or lose one equivalent
of water, respectively, to both yield the stable solvatomorph [Fe(1,3-bpp)2
](ClO4 )2 ?H2 O (2?H2 O), also following SCSC processes. The four derivatives
have been characterised by single-crystal X-ray diffraction (SCXRD). Furthermore,
the homogeneity of the various compounds as well as their SCSC interconversions
have been confirmed by powder X-ray diffraction (PXRD). Polymorphs 1 and 2
exhibit abrupt SCO behaviour near room temperature with T1/2? =279/316 K and
T1/2? =276/314 K (near 40 K of shift) and different cooperativity.
PMID- 27483198
TI - Acute mountain sickness and duration of pre-exposure to high altitude.
PMID- 27483199
TI - Tuning Slow Magnetic Relaxation in a Two-Dimensional Dysprosium Layer Compound
through Guest Molecules.
AB - A novel two-dimensional dysprosium(III) complex,
[Dy(L)(CH3COO)].0.5DMF.H2O.2CH3OH (1), has been successfully synthesized from a
new pyridine-N-oxide (PNO)-containing ligand, namely, N'-(2-hydroxy-3
methoxybenzylidene)pyridine-N-oxidecarbohydrazide (H2L). Single-crystal X-ray
diffraction studies reveal that complex 1 is composed of a dinuclear dysprosium
subunit, which is further extended by the PNO part of the ligand to form a two
dimensional layer. Magnetic studies indicate that complex 1 shows well-defined
temperature- and frequency-dependent signals under a zero direct-current (dc)
field, typical of slow magnetic relaxation with an effective energy barrier Ueff
of 33.6 K under a zero dc field. Interestingly, powder X-ray diffraction and
thermogravimetric analysis reveal that compound 1 undergoes a reversible phase
transition that is induced by the desorption and absorption of methanol and water
molecules. Moreover, the desolvated sample [Dy(L)(CH3COO)].0.5DMF (1a) also
exhibits slow magnetic relaxation but with a higher anisotropic barrier of 42.0
K, indicating the tuning effect of solvent molecules on slow magnetic relaxation.
PMID- 27483200
TI - The Acid and/or Thermal Mediated Ring Contraction of 4H-1,2,6-Thiadiazines To
Afford 1,2,5-Thiadiazoles.
AB - A near-quantitative acid and/or thermal mediated ring contraction of 3',5'
diarylspiro(benzo[d][1,3]dioxole-2,4'-[1,2,6]thiadiazines) affords 3-aryl-4-(2
arylbenzo[d][1,3]dioxol-2-yl)-1,2,5-thiadiazoles. The reaction scope was studied
providing 11 examples of this ring contraction. A double Wagner-Meerwein reaction
mechanism is proposed.
PMID- 27483201
TI - Reply to "Allocation Based on Virtual Crossmatch Alone: Not Yet Ready for
Primetime".
PMID- 27483202
TI - Reply.
PMID- 27483203
TI - Spatiotemporal relationship between adult census size and genetic population size
across a wide population size gradient.
AB - Adult census population size (N) and effective number of breeders (Nb ) are
highly relevant for designing effective conservation strategies. Both parameters
are often challenging to quantify, however, making it of interest to determine
whether one parameter can be generalized from the other. Yet, the spatiotemporal
relationship between N and Nb has not been well characterized empirically in many
taxa. We analysed this relationship for 5-7 consecutive years in twelve brook
trout populations varying greatly in N (49-10032) and Nb (3-567) and identified
major environmental variables affecting the two parameters. N or habitat size
alone explained 47-57% of the variance in Nb , and Nb was strongly correlated
with effective population size. The ratio Nb /N ranged from 0.01 to 0.45 and
increased at small N or following an annual decrease in N, suggesting density
dependent constraints on Nb . We found no evidence for a consistent, directional
difference between variability in Nb and/or Nb /N among small and large
populations; however, small populations had more varying temporal variability in
Nb /N ratios than large populations. Finally, Nb and Nb /N were 2.5- and 2.3-fold
more variable among populations than temporally within populations. Our results
demonstrate a clear linkage between demographic and evolutionary parameters,
suggesting that Nb could be used to approximate N (or vice versa) in natural
populations. Nevertheless, using one variable to infer the other to monitor
trends within populations is less recommended, perhaps even less so in small
populations given their less predictable Nb vs. N dynamics.
PMID- 27483204
TI - Synthetic biology for basic and applied plant research.
PMID- 27483205
TI - Synthetic redesign of plant lipid metabolism.
AB - Plant seed lipid metabolism is an area of intensive research, including many
examples of transgenic events in which oil composition has been modified. In the
selected examples described in this review, progress towards the predictive
manipulation of metabolism and the reconstitution of desired traits in a non
native host is considered. The advantages of a particular oilseed crop, Camelina
sativa, as a flexible and utilitarian chassis for advanced metabolic engineering
and applied synthetic biology are considered, as are the issues that still
represent gaps in our ability to predictably alter plant lipid biosynthesis.
Opportunities to deliver useful bio-based products via transgenic plants are
described, some of which represent the most complex genetic engineering in plants
to date. Future prospects are considered, with a focus on the desire to
transition to more (computationally) directed manipulations of metabolism.
PMID- 27483206
TI - Direct Monitoring of gamma-Glutamyl Transpeptidase Activity In Vivo Using a
Hyperpolarized (13) C-Labeled Molecular Probe.
AB - The gamma-glutamyl transpeptidase (GGT) enzyme plays a central role in
glutathione homeostasis. Direct detection of GGT activity could provide critical
information for the diagnosis of several pathologies. We propose a new molecular
probe, gamma-Glu-[1-(13) C]Gly, for monitoring GGT activity in vivo by
hyperpolarized (HP) (13) C magnetic resonance (MR). The properties of gamma-Glu
[1-(13) C]Gly are suitable for in vivo HP (13) C metabolic analysis since the
chemical shift between gamma-Glu-[1-(13) C]Gly and its metabolic product, [1-(13)
C]Gly, is large (4.3 ppm) and the T1 of both compounds is relatively long (30 s
and 45 s, respectively, in H2 O at 9.4 T). We also demonstrate that gamma-Glu-[1
(13) C]Gly is highly sensitive to in vivo modulation of GGT activity induced by
the inhibitor acivicin.
PMID- 27483207
TI - Mesoporous Carbon Materials with Functional Compositions.
AB - Since the 1990s, there has been rapidly expanding development of solid materials
with mesoporous structure, of which mesoporous carbons are an important family.
Toward the design of functional materials, mesoporous carbons with various
compositions have been prepared for specific uses, such as catalysts, adsorbents,
and electrode materials. Some of those novel materials indeed show promising
performance in several fields, such as nitrogen-doped mesoporous carbon for
oxygen reduction reactions in fuel cells and mesoporous carbon nitride for
photocatalysis. This Minireview summarizes recent advances in the design,
synthesis, characterization, and application of mesoporous carbons with
functional compositions and briefly discusses next-generation mesoporous carbons.
PMID- 27483208
TI - Regional distribution of ventilation in horses in dorsal recumbency during
spontaneous and mechanical ventilation assessed by electrical impedance
tomography: a case series.
AB - OBJECTIVE: To evaluate the regional distribution of ventilation in horses during
spontaneous breathing and controlled mechanical ventilation (CMV) using
electrical impedance tomography (EIT). STUDY DESIGN: Prospective, experimental
case series. ANIMALS: Four anaesthetized experimental horses. METHODS: Horses
were anaesthetized with isoflurane in an oxygen-air mixture and medetomidine
continuous rate infusion, placed in dorsal recumbency with an EIT belt around the
thorax, and allowed to breathe spontaneously until PaCO2 reached 13.3 kPa (100
mmHg), when volume CMV was started. For each horse, the EIT signal was recorded
for at least 2 minutes immediately before (T1), and at 30 (n = 3) or 60 (n = 1)
minutes after the start of CMV (T2). The centre of ventilation (CoV), dependent
silent spaces (DSS) (likely to represent atelectatic lung areas), non-dependent
silent spaces (NSS) (likely to represent lung areas with low ventilation) and
total ventilated area (TVA) were evaluated. Cardiac output (CO) was measured and
venous admixture and oxygen delivery (DO2) were calculated at T1 and T2. Data are
presented as median and range. RESULTS: After the initiation of CMV, the CoV
moved ventrally towards the non-dependent lung by 10% [from 57.4% (49.6-60.2%) to
48.3% (41.9-54.4%)]. DSS increased [from 4.1% (0.2-13.9%) to 18.7% (7.5-27.5%)],
while NSS [21.7% (9.4-29.2%) to 9.9% (1.0-20.7%)] and TVA [920 (699-1051) to 837
(662-961) pixels] decreased. CO, venous admixture and DO2 also decreased.
CONCLUSIONS AND CLINICAL RELEVANCE: In spontaneously breathing anaesthetized
horses in dorsal recumbency, ventilation was essentially centred within the
dependent dorsal lung regions and moved towards non-dependent ventral regions as
soon as CMV was started. This shows a major lack of ventilation in the dependent
lung, which may be indicative of atelectasis.
PMID- 27483209
TI - An Efficient Particle-Based DNA Circuit System: Catalytic Disassembly of DNA/PEG
Modified Gold Nanoparticle-Magnetic Bead Composites for Colorimetric Detection of
miRNA.
AB - An efficient particle-based DNA circuit system for a new colorimetric miRNA assay
is designed and devised based on a catalytic disassembly strategy through a
target miRNA-triggered DNA circuit mechanism. The new particle-based DNA circuit
system shows a rapid color change as well as significant improvement of
sensitivity without need for other enzymes or instruments.
PMID- 27483210
TI - Digital Versus Conventional Impressions in Fixed Prosthodontics: A Review.
AB - PURPOSE: To conduct a systematic review to evaluate the evidence of possible
benefits and accuracy of digital impression techniques vs. conventional
impression techniques. MATERIALS AND METHODS: Reports of digital impression
techniques versus conventional impression techniques were systematically searched
for in the following databases: Cochrane Central Register of Controlled Trials,
PubMed, and Web of Science. A combination of controlled vocabulary, free-text
words, and well-defined inclusion and exclusion criteria guided the search.
RESULTS: Digital impression accuracy is at the same level as conventional
impression methods in fabrication of crowns and short fixed dental prostheses
(FDPs). For fabrication of implant-supported crowns and FDPs, digital impression
accuracy is clinically acceptable. In full-arch impressions, conventional
impression methods resulted in better accuracy compared to digital impressions.
CONCLUSIONS: Digital impression techniques are a clinically acceptable
alternative to conventional impression methods in fabrication of crowns and short
FDPs. For fabrication of implant-supported crowns and FDPs, digital impression
systems also result in clinically acceptable fit. Digital impression techniques
are faster and can shorten the operation time. Based on this study, the
conventional impression technique is still recommended for full-arch impressions.
PMID- 27483211
TI - Are Rheumatoid Factor, Anti-Citrullinated Protein Antibodies, and Anti
Carbamylated Protein Antibodies Linked by Posttranslational Modification of IgG?
Comment on the Article by Koppejan et al.
PMID- 27483212
TI - Generalized Hyperalgesia in Children and Adults Diagnosed With Hypermobility
Syndrome and Ehlers-Danlos Syndrome Hypermobility Type: A Discriminative
Analysis.
AB - OBJECTIVE: Lowered pressure-pain thresholds have been demonstrated in adults with
Ehlers-Danlos syndrome hypermobility type (EDS-HT), but whether these findings
are also present in children is unclear. Therefore, the objectives of the study
were to determine whether generalized hyperalgesia is present in children with
hypermobility syndrome (HMS)/EDS-HT, explore potential differences in pressure
pain thresholds between children and adults with HMS/EDS-HT, and determine the
discriminative value of generalized hyperalgesia. METHODS: Patients were
classified in 1 of 3 groups: HMS/EDS-HT, hypermobile (Beighton score >=4 of 9),
and healthy controls. Descriptive data of age, sex, body mass index, Beighton
score, skin laxity, and medication usage were collected. Generalized hyperalgesia
was quantified by the average pressure-pain thresholds collected from 12
locations. Confounders collected were pain locations/intensity, fatigue, and
psychological distress. Comparisons between children with HMS/EDS-HT and
normative values, between children and adults with HMS/EDS-HT, and corrected
confounders were analyzed with multivariate analysis of covariance. The
discriminative value of generalized hyperalgesia employed to differentiate
between HMS/EDS-HT, hypermobility, and controls was quantified with logistic
regression. RESULTS: Significantly lower pressure-pain thresholds were found in
children with HMS/EDS-HT compared to normative values (range -22.0% to -59.0%; P
<= 0.05). When applying a threshold of 30.8 N/cm2 for males and 29.0 N/cm2 for
females, the presence of generalized hyperalgesia discriminated between
individuals with HMS/EDS-HT, hypermobility, and healthy controls (odds ratio
6.0). CONCLUSION: Children and adults with HMS/EDS-HT are characterized by
hypermobility, chronic pain, and generalized hyperalgesia. The presence of
generalized hyperalgesia may indicate involvement of the central nervous system
in the development of chronic pain.
PMID- 27483213
TI - Ultrasound Mediated One-Pot, Three Component Synthesis, Docking and ADME
Prediction of Novel 5-Amino-2-(4-chlorophenyl)-7-Substituted Phenyl-8,8a-dihydro
7H-(1,3,4)thiadiazolo(3,2-alpha)pyrimidine-6-carbonitrile Derivatives as
Anticancer Agents.
AB - Herein, we report an environmentally friendly, rapid, and convenient one-pot
ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7-substituted phenyl
8,8a-dihydro-7H-(1,3,4)thiadiazolo(3,2-alpha)pyrimidine-6-carbonitrile
derivatives. The in-vitro anticancer activities of these compounds were evaluated
against four human tumor cell lines. Among all the synthesized derivatives,
compound 4i, which has substituent 3-hydroxy-4-methoxyphenyl is found to have the
highest GI50 value of 32.7 MUM, 55.3 MUM, 34.3 MUM, 28.9 MUM for MCF-7, K562,
HeLa and PC-3 cancer cell lines respectively. A docking study of the newly
synthesized compounds were performed, and the results showed good binding mode in
the active site of thymidylate synthase enzyme. ADME properties of synthesized
compounds were also studied and showed good drug like properties.
PMID- 27483214
TI - Influences of Adhesion Variability on the "Living" Dynamics of Filamentous
Bacteria in Microfluidic Channels.
AB - Microfabricated devices have increasingly incorporated bacterial cells for
microscale studies and exploiting cell-based functions in situ. However, the role
of surface interactions in controlling the bacterial cell behavior is not well
understood. In this study, microfluidic substrates of varied bacterial-binding
affinity were used to probe the interaction-driven behavior of filamentous
Escherichia coli. In particular, cell alignment under controlled shear flow as
well as subsequent orientation and filamentation were compared between cells
presenting distinct outer membrane phenotypes. We demonstrated that filaments
retained position under flow, which allowed for dynamic single-cell monitoring
with in situ elongation of over 100 MUm for adherent cells. This maximum was not
reached by planktonic cells and was, therefore, adhesion-dependent. The bound
filaments initially aligned with flow under a range of flow rates and their
continual elongation was traced in terms of length and growth path; analysis
demonstrated that fimbriae-mediated adhesion increased growth rate, increased
terminal length, as well as dramatically changed the adherent geometry,
particularly buckling behavior. The effects to filament length and buckling were
further exaggerated by the strongest, specificity-driven adhesion tested. Such
surface-guided control of the elongation process may be valuable to yield
interesting "living" filamentous structures in microdevices. In addition, this
work may offer a biomedically relevant platform for further elucidation of
filamentation as an immune-resistant morphology. Overall, this work should
inspire broader exploration of microfabricated devices for the study and
application of single bacterial cells.
PMID- 27483215
TI - Native Mass Spectrometry in Fragment-Based Drug Discovery.
AB - The advent of native mass spectrometry (MS) in 1990 led to the development of new
mass spectrometry instrumentation and methodologies for the analysis of
noncovalent protein-ligand complexes. Native MS has matured to become a fast,
simple, highly sensitive and automatable technique with well-established utility
for fragment-based drug discovery (FBDD). Native MS has the capability to
directly detect weak ligand binding to proteins, to determine stoichiometry,
relative or absolute binding affinities and specificities. Native MS can be used
to delineate ligand-binding sites, to elucidate mechanisms of cooperativity and
to study the thermodynamics of binding. This review highlights key attributes of
native MS for FBDD campaigns.
PMID- 27483216
TI - Bioactive Molecule Prediction Using Extreme Gradient Boosting.
AB - Following the explosive growth in chemical and biological data, the shift from
traditional methods of drug discovery to computer-aided means has made data
mining and machine learning methods integral parts of today's drug discovery
process. In this paper, extreme gradient boosting (Xgboost), which is an ensemble
of Classification and Regression Tree (CART) and a variant of the Gradient
Boosting Machine, was investigated for the prediction of biological activity
based on quantitative description of the compound's molecular structure. Seven
datasets, well known in the literature were used in this paper and experimental
results show that Xgboost can outperform machine learning algorithms like Random
Forest (RF), Support Vector Machines (LSVM), Radial Basis Function Neural Network
(RBFN) and Naive Bayes (NB) for the prediction of biological activities. In
addition to its ability to detect minority activity classes in highly imbalanced
datasets, it showed remarkable performance on both high and low diversity
datasets.
PMID- 27483217
TI - N,N'-Bis(2-cyclohexylethyl)naphtho[2,3-b:6,7-b']dithiophene Diimides: Effects of
Substituents.
AB - Naphtho[2,3-b:6,7-b']dithiophene-4,5,9,10-tetracarboxylic diimide (NDTI) is a
promising electron-deficient building block for n-type organic conductors, and
the performance of NDTI-based field-effect transistors (FETs) is largely
dependent on the substituents that alter the supramolecular organization in the
solid state and, in turn, the intermolecular orbital overlap. For this reason,
the rational selection of substituent on imide nitrogen atoms and/or thiophene
alpha-positions is the key to developing superior n-type organic semiconductors.
We here report new NDTI derivatives having N-(2-cyclohexylethyl) groups. Despite
their one-dimensional packing structures in the solid state regardless of the
presence or absence of chlorine groups at the thiophene alpha-positions, their
FETs show promising performance with electron mobilities higher than 0.1 cm2.V(
1).s(-1) under ambient conditions. We also discuss how the cyclohexylethyl groups
affect the packing structure in comparison with analogous n-octyl derivatives
having the same number of carbon atoms.
PMID- 27483218
TI - Lutein, a Natural Carotenoid, Induces alpha-1,3-Glucan Accumulation on the Cell
Wall Surface of Fungal Plant Pathogens.
AB - alpha-1,3-Glucan, a component of the fungal cell wall, is a refractory
polysaccharide for most plants. Previously, we showed that various fungal plant
pathogens masked their cell wall surfaces with alpha-1,3-glucan to evade plant
immunity. This surface accumulation of alpha-1,3-glucan was infection specific,
suggesting that plant factors might induce its production in fungi. Through
immunofluorescence observations of fungal cell walls, we found that carrot
(Daucus carota) extract induced the accumulation of alpha-1,3-glucan on germlings
in Colletotrichum fioriniae, a polyphagous fungal pathogen that causes
anthracnose disease in various dicot plants. Bioassay-guided fractionation of
carrot leaf extract successfully identified two active substances that caused
alpha-1,3-glucan accumulation in this fungus: lutein, a carotenoid widely
distributed in plants, and stigmasterol, a plant-specific membrane component.
Lutein, which had a greater effect on C. fioriniae, also induced alpha-1,3-glucan
accumulation in other Colletotrichum species and in the phylogenetically distant
rice pathogen Cochliobolus miyabeanus, but not in the rice pathogen Magnaporthe
oryzae belonging to the same phylogenetic subclass as Colletotrichum. Our results
suggested that fungal plant pathogens reorganize their cell wall components in
response to specific plant-derived compounds, which these pathogens may encounter
during infection.
PMID- 27483219
TI - Coffee Consumption and Oxidative Stress: A Review of Human Intervention Studies.
AB - Research on the potential protective effects of coffee and its bioactives
(caffeine, chlorogenic acids and diterpenes) against oxidative stress and related
chronic disease risk has been increasing in the last years. The present review
summarizes the main findings on the effect of coffee consumption on protection
against lipid, protein and DNA damage, as well as on the modulation of
antioxidant capacity and antioxidant enzymes in human studies. Twenty-six dietary
intervention studies (involving acute and chronic coffee intake) have been
considered. Overall, the results suggest that coffee consumption can increase
glutathione levels and improve protection against DNA damage, especially
following regular/repeated intake. On the contrary, the effects of coffee on
plasma antioxidant capacity and antioxidant enzymes, as well as on protein and
lipid damage, are unclear following both acute and chronic exposure. The high
heterogeneity in terms of type of coffee, doses and duration of the studies, the
lack of information on coffee and/or brew bioactive composition, as well as the
choice of biomarkers and the methods used for their evaluation, may partially
explain the variability observed among findings. More robust and well-controlled
intervention studies are necessary for a thorough understanding of the effect of
coffee on oxidative stress markers in humans.
PMID- 27483220
TI - Efficacy of Acetylshikonin in Preventing Obesity and Hepatic Steatosis in db/db
Mice.
AB - Zicao (Lithospermum erythrorhizon) has been used in clinics as a traditional
Chinese medicine for thousands of years. Acetylshikonin (AS) is the main
ingredient of Zicao, Xinjiang, China. The objective of this study was to
investigate the anti-obesity and anti-nonalcoholic fatty liver disease (NAFLD)
efficacy of AS in a model of spontaneous obese db/db mice. Mice were divided into
Wild Type (WT) groups and db/db groups, which received no treatment or treatment
with 100 mg/kg/day clenbuterol (CL) hydrochloride or 540 mg/kg/day AS by oral
gavage for eight weeks. The results provided the evidence that AS prevented
obesity and NAFLD including reduction in body weight, food efficiency ratio,
serum triglyceride (TG) and free fatty acid (FFA) levels in db/db mice.
Administration of AS markedly suppressed the levels of hepatic alanine
aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory
cytokines in treated groups when compared with that of db/db groups. Further
investigation of the lipid synthesis-related protein using Western blotting
revealed that hepatic protein expression of sterol regulatory element-binding
protein-1 (SREBP-1), fatty acid synthetase (FAS) and 3-hydroxy-3-methylglutaryl
coenzyme A reductase (HMGCR) were significantly downregulated by AS treatment.
These findings suggest that AS exerts anti-obesity and anti-NAFLD effects through
the regulation of lipid metabolism and anti-inflammatory effects.
PMID- 27483221
TI - In Vitro Neuroprotective and Anti-Inflammatory Activities of Natural and Semi
Synthetic Spirosteroid Analogues.
AB - Two spirosteroid analogues were synthesized and evaluated for their in vitro
neuroprotective activities in PC12 cells, against glutamate-induced
excitotoxicity and mitochondrial damage in glucose deprivation conditions, as
well as their anti-inflammatory potential in LPS/IFNgamma-stimulated microglia
primary cultures. We also evaluated the in vitro anti-excitotoxic and anti
inflammatory activities of natural and endogenous steroids. Our results show that
the plant-derived steroid solasodine decreased PC12 glutamate-induced
excitotoxicity, but not the cell death induced by mitochondrial damage and
glucose deprivation. Among the two synthetic spirosteroid analogues, only the
(25R)-5alpha-spirostan-3,6-one (S15) protected PC12 against ischemia-related in
vitro models and inhibited NO production, as well as the release of IL-1beta by
stimulated primary microglia. These findings provide further insights into the
role of specific modifications of the A and B rings of sapogenins for their
neuroprotective potential.
PMID- 27483222
TI - Recent Advances in Metal-Free Quinoline Synthesis.
AB - The quinoline ring system is one of the most ubiquitous heterocycles in the
fields of medicinal and industrial chemistry, forming the scaffold for compounds
of great significance. These include anti-inflammatory and antitumor agents, the
antimalarial drugs quinine and chloroquine, and organic light-emitting diodes.
Quinolines were first synthesized in 1879, and since then a multitude of
synthetic routes have been developed. Many of these methods, such as the Skraup,
Doebner-Von Miller, and Friedlander quinoline syntheses, are well-known but
suffer from inefficiency, harsh reaction conditions, and toxic reagents. This
review focuses on recent transition metal-free processes toward these important
heterocycles, including both novel routes and modifications to established
methods. For example, variations on the Skraup method include microwave
irradiation, ionic liquid media, and novel annulation partners, all of which have
shown increased reaction efficiency and improved yield of the heteroring
unsubstituted quinoline products. Similarly, modifications to other synthetic
routes have been implemented, with the quinoline products displaying a wide
variety of substitution patterns.
PMID- 27483223
TI - Isolation of a Cyclic (Alkyl)(amino)germylene.
AB - A 1,4-addition of a dichlorogermylene dioxane complex with alpha,beta-unsaturated
imine 1 gave a dichlorogermane derivative 2 bearing a GeC3N five-membered ring
skeleton. By reducing 2 with KC8, cyclic (alkyl)(amino)germylene 3 was
synthesized and fully characterized. Germylene 3 readily reacted with TEMPO, N2O
and S8, producing the 1:2 adduct 4, the oxo-bridged dimer 5 and the sulfido
bridged dimer 6, respectively.
PMID- 27483224
TI - Prenylated Chalcone 2 Acts as an Antimitotic Agent and Enhances the
Chemosensitivity of Tumor Cells to Paclitaxel.
AB - We previously reported that prenylated chalcone 2 (PC2), the O-prenyl derivative
(2) of 2'-hydroxy-3,4,4',5,6'-pentamethoxychalcone (1), induced cytotoxicity of
tumor cells via disruption of p53-MDM2 interaction. However, the cellular changes
through which PC2 exerts its cytotoxic activity and its antitumor potential,
remain to be addressed. In the present work, we aimed to (i) characterize the
effect of PC2 on mitotic progression and the underlying mechanism; and to (ii)
explore this information to evaluate its ability to sensitize tumor cells to
paclitaxel in a combination regimen. PC2 was able to arrest breast adenocarcinoma
MCF-7 and non-small cell lung cancer NCI-H460 cells in mitosis. All mitosis
arrested cells showed collapsed mitotic spindles with randomly distributed
chromosomes, and activated spindle assembly checkpoint. Live-cell imaging
revealed that the compound induced a prolonged delay (up to 14 h) in mitosis,
culminating in massive cell death by blebbing. Importantly, PC2 in combination
with paclitaxel enhanced the effect on cell growth inhibition as determined by
cell viability and proliferation assays. Our findings demonstrate that the
cytotoxicity induced by PC2 is mediated through antimitotic activity as a result
of mitotic spindle damage. The enhancement effects of PC2 on chemosensitivity of
cancer cells to paclitaxel encourage further validation of the clinical potential
of this combination.
PMID- 27483225
TI - Chemo-Enzymatic Synthesis of Chiral Epoxides Ethyl and Methyl (S)-3-(Oxiran-2
yl)propanoates from Renewable Levoglucosenone: An Access to Enantiopure (S)-Dairy
Lactone.
AB - Chiral epoxides-such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)
1a/1b)-are valuable precursors in many chemical syntheses. Until recently, these
compounds were synthesized from glutamic acid in four steps (deamination,
reduction, tosylation and epoxide formation) in low to moderate overall yield
(20%-50%). Moreover, this procedure requires some harmful reagents such as sodium
nitrite ((eco)toxic) and borane (carcinogen). Herein, starting from
levoglucosenone (LGO), a biobased chiral compound obtained through the flash
pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo
enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation,
palladium-catalyzed hydrogenation, tosylation and treatment with sodium
ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S)-3
(oxiran-2-yl)propanoates in 57% overall yield, respectively. To demonstrate the
potentiality of this new synthetic pathway from LGO, the synthesis of high value
added (S)-dairy lactone was undertaken from these epoxides and provided the
target in 37% overall yield from LGO.
PMID- 27483226
TI - A Well-Defined {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} Complex Catalyzed Hiyama
Coupling of Aryl Bromides with Arylsilanes.
AB - A palladium (II) complex {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} catalyzed Hiyama
cross-coupling reaction between aryl bromides and arylsilanes has been developed.
The substituted biaryls were produced in moderate to high yields, regardless of
electron-withdrawing or electron-donating.
PMID- 27483227
TI - Selective Extraction of Flavonoids from Sophora flavescens Ait. by
Mechanochemistry.
AB - Flavonoids from Sophora flavescens were selectively extracted by mechanochemical
promoted extraction technology (MPET) after using response surface methodology to
determine the optimal extraction parameters. The highest yield of 35.17 mg/g was
achieved by grinding the roots with Na2CO3 (15%) at 440 rpm/min for 17.0 min and
water was used as the sole solvent with a ratio of solvent to solid material of
25 mL/g. Flavonoids prepared by MPET demonstrated relatively higher antioxidant
activities in subsequent DPPH and hydroxyl radical scavenging assays. Main
constituents in the extracts, including kurarinol, kushenol I/N and kurarinone,
were characterized by HPLC-MS/MS, indicating good selective extraction by MPET.
Physicochemical property changes of powder during mechanochemical milling were
identified by scanning electron microscopy, X-ray powder diffraction, and UV-Vis
diffuse-reflectance spectroscopy. Compared with traditional extraction methods,
MPET possesses notable advantages of higher selectivity, lower extraction
temperature, shorter extraction time, and organic solvent free properties.
PMID- 27483228
TI - Chemical Composition and Inhibitory Effect of Lentinula edodes Ethanolic Extract
on Experimentally Induced Atopic Dermatitis in Vitro and in Vivo.
AB - The ethanolic extract of Lentinula edodes was partially analyzed and then
characterized for its efficacy in treating atopic dermatitis. Polyphenols were
determined to be the major antioxidant component in the extract (6.12 mg/g),
followed by flavonoids (1.76 mg/g), beta-carotene (28.75 MUg/g), and lycopene
(5.25 MUg/g). An atopic dermatitis (AD) model was established and epidermal and
dermal ear thickness, mast cell infiltration, and serum immunoglobulin levels
were measured after oral administration of the L. edodes extract for 4 weeks. L.
edodes extract decreased Dermatophagoides farinae extract (DFE) and 4
dinitrochlorobenzene (DNCB)-induced expression of several inflammatory cytokines
in the ears, cervical lymph nodes, and splenocytes. Consequently, L. edodes
extract may have therapeutic potential in the treatment of AD attributable to its
immunomodulatory effects.
PMID- 27483229
TI - Phenylethanoid Glycosides: Research Advances in Their Phytochemistry,
Pharmacological Activity and Pharmacokinetics.
AB - Phenylethanoid glycosides (PhGs) are widely distributed in traditional Chinese
medicines as well as in other medicinal plants, and they were characterized by a
phenethyl alcohol (C6-C2) moiety attached to a beta-glucopyranose/beta
allopyranose via a glycosidic bond. The outstanding activity of PhGs in diverse
diseases proves their importance in medicinal chemistry research. This review
summarizes new findings on PhGs over the past 10 years, concerning the new
structures, their bioactivities, including neuroprotective, anti-inflammatory,
antioxidant, antibacterial and antivirus, cytotoxic, immunomodulatory, and enzyme
inhibitory effects, and pharmacokinetic properties.
PMID- 27483230
TI - Antioxidant Capacities of Fractions of Bamboo Shaving Extract and Their
Antioxidant Components.
AB - This research was conducted for evaluation of antioxidant activities of four
fractions from bamboo shavings extract (BSE) and their antioxidant components.
The antioxidant capacities of BSE and four fractions on ABTS, DPPH, FRAP and
total antioxidant capacity assays exhibited the following descending order: DF >
n-butanol fraction (BF) > BSE ~ ethyl acetate fraction (AF) > water fraction
(WF). Among the identified phenolic compounds, caffeic acid exhibited the highest
antioxidant capacities on DPPH, FRAP and total antioxidant capacity assays. An
extremely significant positive correlation between the antioxidant activities
with the contents of total flavonoids, total phenolic acids, or total phenolics
was observed in this study. The result indicated that the bamboo shaving extract
and its solvent fractions could act as natural antioxidants in light of their
potent antioxidant activities.
PMID- 27483231
TI - Computational Approaches to Toll-Like Receptor 4 Modulation.
AB - Toll-like receptor 4 (TLR4), along with its accessory protein myeloid
differentiation factor 2 (MD-2), builds a heterodimeric complex that specifically
recognizes lipopolysaccharides (LPS), which are present on the cell wall of Gram
negative bacteria, activating the innate immune response. Some TLR4 modulators
are undergoing preclinical and clinical evaluation for the treatment of sepsis,
inflammatory diseases, cancer and rheumatoid arthritis. Since the relatively
recent elucidation of the X-ray crystallographic structure of the extracellular
domain of TLR4, research around this fascinating receptor has risen to a new
level, and thus, new perspectives have been opened. In particular, diverse
computational techniques have been applied to decipher some of the basis at the
atomic level regarding the mechanism of functioning and the ligand recognition
processes involving the TLR4/MD-2 system at the atomic level. This review
summarizes the reported molecular modeling and computational studies that have
recently provided insights into the mechanism regulating the
activation/inactivation of the TLR4/MD-2 system receptor and the key interactions
modulating the molecular recognition process by agonist and antagonist ligands.
These studies have contributed to the design and the discovery of novel small
molecules with promising activity as TLR4 modulators.
PMID- 27483232
TI - Pro-Apoptotic Activity of New Honokiol/Triphenylmethane Analogues in B-Cell
Lymphoid Malignancies.
AB - Honokiol and triphenylmethanes are small molecules with anti-tumor properties.
Recently, we synthesized new honokiol analogues (HAs) that possess common
features of both groups. We assessed the anti-tumor effectiveness of HAs in B
cell leukemia/lymphoma cells, namely in chronic lymphocytic leukemia (CLL) cells
ex vivo and in pre-B-cell acute lymphoblastic leukemia (Nalm-6), Burkitt lymphoma
(BL; Raji), diffuse large B-cell lymphoma (DLBCL; Toledo) and multiple myeloma
(MM; RPMI 8226) cell lines. Four of these compounds appeared to be significantly
active against the majority of cells examined, with no significant impact on
healthy lymphocytes. These active HAs induced caspase-dependent apoptosis,
causing significant deregulation of several apoptosis-regulating proteins.
Overall, these compounds downregulated Bcl-2 and XIAP and upregulated Bax, Bak
and survivin proteins. In conclusion, some of the HAs are potent tumor-selective
inducers of apoptosis in ex vivo CLL and in BL, DLBCL and MM cells in vitro.
Further preclinical studies of these agents are recommended.
PMID- 27483233
TI - A General Catalytic Enantioselective Transfer Hydrogenation Reaction of beta,beta
Disubstituted Nitroalkenes Promoted by a Simple Organocatalyst.
AB - Given its synthetic relevance, the catalytic enantioselective reduction of
beta,beta-disubstituted nitroalkenes has received a great deal of attention.
Several bio-, metal-, and organo-catalytic methods have been developed, which
however are usually applicable to single classes of nitroalkene substrates. In
this paper, we present an account of our previous work on this transformation,
which implemented with new disclosures and mechanistic insights results in a very
general protocol for nitroalkene reductions. The proposed methodology is
characterized by (i) a remarkably broad scope encompassing various nitroalkene
classes; (ii) Hantzsch esters as convenient (on a preparative scale) hydrogen
surrogates; (iii) a simple and commercially available thiourea as catalyst; (iv)
user-friendly procedures. Overall, the proposed protocol gives a practical
dimension to the catalytic enantioselective reduction of beta,beta-disubstituted
nitroalkenes, offering a useful and general platform for the preparation of
nitroalkanes bearing a stereogenic center at the beta-position in a highly
enantioenriched form. A transition state model derived from control kinetic
experiments combined with literature data is proposed and discussed. This model
accounts and justifies the observed experimental results.
PMID- 27483234
TI - Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery:
Future Implications for Ocular Delivery.
AB - Therapeutic proteins and peptides have become notable in the drug delivery arena
for their compatibility with the human body as well as their high potency.
However, their biocompatibility and high potency does not negate the existence of
challenges resulting from physicochemical properties of proteins and peptides,
including large size, short half-life, capability to provoke immune responses and
susceptibility to degradation. Various delivery routes and delivery systems have
been utilized to improve bioavailability, patient acceptability and reduce
biodegradation. The ocular route remains of great interest, particularly for
responsive delivery of macromolecules due to the anatomy and physiology of the
eye that makes it a sensitive and complex environment. Research in this field is
slowly gaining attention as this could be the breakthrough in ocular drug
delivery of macromolecules. This work reviews stimuli-responsive polymeric
delivery systems, their use in the delivery of therapeutic proteins and peptides
as well as examples of proteins and peptides used in the treatment of ocular
disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound
and magnetic field. In addition, it discusses the current progress in responsive
ocular drug delivery. Furthermore, it explores future prospects in the use of
stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli
responsive polymers offer great potential in improving the delivery of ocular
therapeutics, therefore there is a need to consider them in order to guarantee a
local, sustained and ideal delivery of ocular proteins and peptides, evading
tissue invasion and systemic side-effects.
PMID- 27483235
TI - The in Vitro and in Vivo Antitumor Activities of Tetracyclic Triterpenoids
Compounds Actein and 26-Deoxyactein Isolated from Rhizome of Cimicifuga foetida
L.
AB - AIMS: This work aims to study the in vitro and in vivo antitumor activities of
tetracyclic triterpenoids compounds actein and 26-deoxyactein. Further, the
mechanism is investigated. METHODS: In vitro, a modified MTT method was used to
assay the cytotoxicities of actein and 26-deoxyactein in 12 human tumor cell
lines. In vivo, mouse sarcoma S180 and human lung cancer A549 cells were
respectively implanted subcutaneously in ICR mice and nude mice to establish
implanted tumor models. Flow cytometry (FCM) was used to assay the cycle
distribution of the tumor cells. Immunohistochemistry was used to measure CD31
positive expression in the xenogrft tumor by analyzing microvessel density (MVD).
In addition, acute toxicities of actein and 26-deoxyactein were also evaluated.
RESULTS: Actein and 26-deoxyactein inhibited the proliferation of the 12 human
cancer cell lines tested with the values of 50% inhibitory concentrations (IC50)
between 12.29 and 88.39 MUg/mL. In vivo, both actein (3-27 mg/kg) and 26
deoxyactein (3-27 mg/kg) significantly inhibited the growth of the implanted
sarcoma S180 in a dose-dependent manner. Actein (10, 30 mg/kg) and 26-deoxyactein
(10, 30 mg/kg) markedly inhibited the xenograft growth with T/C (%) values of
38%, 55% for actein, and 35%, 49% for 26-deoxyactein. Compared with the vehicle
control, actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) significantly
reduced the MVD in the xenograft tumor. The FCM result showed that human leukemia
HL-60 cells were arrested at G1 phase after treated with either actein (6.25-25
MUg/mL) or 26-deoxyactein (6.25-25 MUg/mL) for 48 h. A limited trial in mice
showed that both of the minimal lethal doses (MLDs) of actein and 26-deoxyactein
were over 5 g/kg. CONCLUSIONS: Both actein and 26-deoxyactein have low
toxicities. Importantly, both these two tetracyclic triterpenoids compounds
isolated from rhizome of Cimicifuga foetida L. have significant antitumor
activities in vitro and in vivo, which is associated with cell cycle arrest and
angiogenesis inhibition.
PMID- 27483236
TI - Antiproliferative and Pro-Apoptotic Effect of Novel Nitro-Substituted
Hydroxynaphthanilides on Human Cancer Cell Lines.
AB - Ring-substituted hydroxynaphthanilides are considered as cyclic analogues of
salicylanilides, compounds possessing a wide range of pharmacological activities,
including promising anticancer properties. The aim of this study was to evaluate
the potential anticancer effect of novel nitro-substituted hydroxynaphthanilides
with a special focus on structure-activity relationships. The antiproliferative
effect was assessed by Water Soluble Tetrazolium Salts-1 (WST-1) assay, and
cytotoxicity was evaluated via dye exclusion test. Flow cytometry was used for
cell cycle analysis and detection of apoptosis using Annexin V-FITC/PI assay.
Protein expression was estimated by Western blotting. Our data indicate that the
potential to cause the antiproliferative effect increases with the shift of the
nitro substituent from the ortho- to the para-position. The most potent
compounds, 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide (2), and 2
hydroxy-N-(4-nitrophenyl)-naphthalene-1-carboxamide (6) showed antiproliferative
activity against THP-1 and MCF-7 cancer cells without affecting the proliferation
of 3T3-L1 non-tumour cells. Compounds 2 and 6 induced the accumulation of THP-1
and MCF-7 cells in G1 phase associated with the downregulation of cyclin E1
protein levels, while the levels of cyclin B1 were not affected. Moreover,
compound 2 was found to exert the pro-apoptotic effect on the THP-1 cells. These
results suggest that hydroxynaphthanilides might represent a potential model
structure for the development of novel anticancer agents.
PMID- 27483237
TI - Genome-Wide Identification and Characterization of Carboxypeptidase Genes in
Silkworm (Bombyx mori).
AB - The silkworm (Bombyx mori) is an economically-important insect that can secrete
silk. Carboxypeptidases have been found in various metazoan species and play
important roles in physiological and biochemical reactions. Here, we analyzed the
silkworm genome database and characterized 48 carboxypeptidases, including 34
metal carboxypeptidases (BmMCP1-BmMCP34) and 14 serine carboxypeptidases (BmSCP1
BmSCP14), to better understand their diverse functions. Compared to other
insects, our results indicated that carboxypeptidases from silkworm have more
family members. These silkworm carboxypeptidases could be divided into four
families: Peptidase_M2 carboxypeptidases, Peptidase_M14 carboxypeptidases,
Peptidase_S10 carboxypeptidases and Peptidase_S28 carboxypeptidases. Microarray
analysis showed that the carboxypeptidases had distinct expression patterns,
whereas quantitative real-time PCR demonstrated that the expression level of 13
carboxypeptidases significantly decreased after starvation and restored after re
feeding. Overall, our study provides new insights into the functional and
evolutionary features of silkworm carboxypeptidases.
PMID- 27483238
TI - Screening and Validation of Housekeeping Genes of the Root and Cotyledon of
Cunninghamia lanceolata under Abiotic Stresses by Using Quantitative Real-Time
PCR.
AB - Cunninghamia lanceolata (Chinese fir) is a fast-growing and commercially
important conifer of the Cupressaceae family. Due to the unavailability of
complete genome sequences and relatively poor genetic background information of
the Chinese fir, it is necessary to identify and analyze the expression levels of
suitable housekeeping genes (HKGs) as internal reference for precise analysis.
Based on the results of database analysis and transcriptome sequencing, we have
chosen five candidate HKGs (Actin, GAPDH, EF1a, 18S rRNA, and UBQ) with
conservative sequences in the Chinese fir and related species for quantitative
analysis. The expression levels of these HKGs in roots and cotyledons under five
different abiotic stresses in different time intervals were measured by qRT-PCR.
The data were statistically analyzed using the following algorithms: NormFinder,
BestKeeper, and geNorm. Finally, RankAggreg was applied to merge the sequences
generated from three programs and rank these according to consensus sequences.
The expression levels of these HKGs showed variable stabilities under different
abiotic stresses. Among these, Actin was the most stable internal control in
root, and GAPDH was the most stable housekeeping gene in cotyledon. We have also
described an experimental procedure for selecting HKGs based on the de novo
sequencing database of other non-model plants.
PMID- 27483239
TI - Full-Length cDNA Cloning, Molecular Characterization and Differential Expression
Analysis of Lysophospholipase I from Ovis aries.
AB - Lysophospholipase I (LYPLA1) is an important protein with multiple functions. In
this study, the full-length cDNA of the LYPLA1 gene from Ovis aries (OaLypla1)
was cloned using primers and rapid amplification of cDNA ends (RACE) technology.
The full-length OaLypla1 was 2457 bp with a 5'-untranslated region (UTR) of 24
bp, a 3'-UTR of 1740 bp with a poly (A) tail, and an open reading frame (ORF) of
693 bp encoding a protein of 230 amino acid residues with a predicted molecular
weight of 24,625.78 Da. Phylogenetic analysis showed that the OaLypla1 protein
shared a high amino acid identity with LYPLA1 of Bos taurus. The recombinant
OaLypla1 protein was expressed and purified, and its phospholipase activity was
identified. Monoclonal antibodies (mAb) against OaLypla1 that bound native
OaLypla1 were generated. Real-time PCR analysis revealed that OaLypla1 was
constitutively expressed in the liver, spleen, lung, kidney, and white blood
cells of sheep, with the highest level in the kidney. Additionally, the mRNA
levels of OaLypla1 in the buffy coats of sheep challenged with virulent or
avirulent Brucella strains were down-regulated compared to untreated sheep. The
results suggest that OaLypla1 may have an important physiological role in the
host response to bacteria. The function of OaLypla1 in the host response to
bacterial infection requires further study in the future.
PMID- 27483240
TI - Minocycline Loaded Hybrid Composites Nanoparticles for Mesenchymal Stem Cells
Differentiation into Osteogenesis.
AB - Bone transplants are used to treat fractures and increase new tissue development
in bone tissue engineering. Grafting of massive implantations showing slow curing
rate and results in cell death for poor vascularization. The potentials of
biocomposite scaffolds to mimic extracellular matrix (ECM) and including new
biomaterials could produce a better substitute for new bone tissue formation. A
purpose of this study is to analyze polycaprolactone/silk fibroin/hyaluronic
acid/minocycline hydrochloride (PCL/SF/HA/MH) nanoparticles initiate human
mesenchymal stem cells (MSCs) proliferation and differentiation into
osteogenesis. Electrospraying technique was used to develop PCL, PCL/SF,
PCL/SF/HA and PCL/SF/HA/MH hybrid biocomposite nanoparticles and characterization
was analyzed by field emission scanning electron microscope (FESEM), contact
angle and Fourier transform infrared spectroscopy (FT-IR). The obtained results
proved that the particle diameter and water contact angle obtained around 0.54 +/
0.12 to 3.2 +/- 0.18 um and 43.93 +/- 10.8 degrees to 133.1 +/- 12.4 degrees
respectively. The cell proliferation and cell-nanoparticle interactions analyzed
using (3-(4,5-dimethyl thiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)
2H-tetrazolium inner salt) MTS assay (Promega, Madison, WI, USA), FESEM for cell
morphology and 5-Chloromethylfluorescein diacetate (CMFDA) dye for imaging live
cells. Osteogenic differentiation was proved by expression of osteocalcin,
alkaline phosphatase activity (ALP) and mineralization was confirmed by using
alizarin red (ARS). The quantity of cells was considerably increased in
PCL/SF/HA/MH nanoparticles when compare to all other biocomposite nanoparticles
and the cell interaction was observed more on PCL/SF/HA/MH nanoparticles. The
electrosprayed PCL/SF/HA/MH biocomposite nanoparticle significantly initiated
increased cell proliferation, osteogenic differentiation and mineralization,
which provide huge potential for bone tissue engineering.
PMID- 27483241
TI - A Female-Biased Odorant Receptor from Apolygus lucorum (Meyer-Dur) Tuned to Some
Plant Odors.
AB - Apolygus lucorum (Meyer-Dur) (Hemiptera: Miridae) is a serious pest of cotton,
jujube, grape and many other crops around the world. Understanding how olfactory
information directs this insect to its host plants may provide environment
friendly approaches to the control of its population in agriculture. In our
study, we cloned an odorant receptor gene, AlucOR46, that was specifically
expressed in antennae and female-biased. Functional expression of AlucOR46 in
Xenopus oocytes showed that it is tuned to six plant volatiles (S)-(-)-Limonene,
(R)-(+)-Limonene, (E)-2-Hexenal, (E)-3-Hexenol, 1-Heptanol and (1R)-(-)-Myrtenol.
Electroantennogram (EAG) recordings revealed that all six compounds could elicit
electrophysiological responses from the antennae of A. lucorum, higher in
females. Our results are in agreement with previous reports showing that (E)-2
Hexenal could attract female A. lucorum in behavior experiments. These results
suggest that AlucOR46 might play an important role in locating the host plants of
A. lucorum and therefore represents a suitable target for green pest control.
PMID- 27483242
TI - Theoretical and Kinetic Tools for Selecting Effective Antioxidants: Application
to the Protection of Omega-3 Oils with Natural and Synthetic Phenols.
AB - Radical-scavenging antioxidants play crucial roles in the protection of
unsaturated oils against autoxidation and, especially, edible oils rich in omega
3 because of their high sensitivity to oxygen. Two complementary tools are
employed to select, among a large set of natural and synthetic phenols, the most
promising antioxidants. On the one hand, density functional theory (DFT)
calculations provide bond dissociation enthalpies (BDEs) of 70 natural (i.e.,
tocopherols, hydroxybenzoic and cinnamic acids, flavonoids, stilbenes, lignans,
and coumarins) and synthetic (i.e., 2,6-di-tert-butyl-4-methylphenol (BHT), 3
tert-butyl-4-hydroxyanisol (BHA), and tert-butylhydroquinone (TBHQ)) phenols.
These BDEs are discussed on the basis of structure-activity relationships with
regard to their potential antioxidant activities. On the other hand, the kinetic
rate constants and number of hydrogen atoms released per phenol molecule are
measured by monitoring the reaction of phenols with 2,2-diphenyl-1-picrylhydrazyl
(DPPH(*)) radical. The comparison of the results obtained with these two
complementary methods allows highlighting the most promising antioxidants.
Finally, the antioxidant effectiveness of the best candidates is assessed by
following the absorption of oxygen by methyl esters of linseed oil containing 0.5
mmol L(-1) of antioxidant and warmed at 90 degrees C under oxygen atmosphere.
Under these conditions, some natural phenols namely epigallocatechin gallate,
myricetin, rosmarinic and carnosic acids were found to be more effective
antioxidants than alpha-tocopherol.
PMID- 27483243
TI - Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2
Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468
Cells as Apoptosis-Inducing Agents.
AB - On account of its poor prognosis and deficiency of therapeutic stratifications,
triple negative breast cancer continues to form the causative platform of an
incommensurate number of breast cancer deaths. Aiming at the development of
potent anticancer agents as a continuum of our previous efforts, a novel series
of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-w was synthesized and
evaluated for its anti-proliferative activity towards triple negative breast
cancer (TNBC) MDA-MB-468 cells. Compound 5k was the most active analog against
MDA-MB-468 (IC50 = 19.90 +/- 1.37 uM), with 2.1-fold increased activity compared
to 5-fluorouracil (IC50 = 41.26 +/- 3.77 uM). Compound 5k was able to induce
apoptosis in MDA-MB-468, as evidenced by the marked boosting in the percentage of
florecsein isothiocyanate annexin V (Annexin V-FITC)-positive apoptotic cells
(upper right (UR) + lower right (LR)) by 2.8-fold in comparison to control
accompanied by significant increase in the proportion of cells at pre-G1 (the
first gap phase) by 8.13-fold in the cell-cycle analysis. Moreover, a
quantitative structure activity relationship (QSAR) model was established to
investigate the structural requirements orchestrating the anti-proliferative
activity. Finally, we established a theoretical kinetic study.
PMID- 27483245
TI - Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and
Clinical Evidence.
AB - An increase in the rates of morbidity and mortality associated with diabetic
complications is a global concern. Glycemic control is important to prevent the
development and progression of diabetic complications. Various classes of anti
diabetic agents are currently available, and their pleiotropic effects on
diabetic complications have been investigated. Incretin-based therapies such as
dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor
agonists (GLP-1RA) are now widely used in the treatment of patients with type 2
diabetes. A series of experimental studies showed that incretin-based therapies
have beneficial effects on diabetic complications, independent of their glucose
lowering abilities, which are mediated by anti-inflammatory and anti-oxidative
stress properties. Based on these findings, clinical studies to assess the
effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and
macrovascular complications have been performed. Several but not all studies have
provided evidence to support the beneficial effects of incretin-based therapies
on diabetic complications in patients with type 2 diabetes. We herein discuss the
experimental and clinical evidence of incretin-based therapy for diabetic
complications.
PMID- 27483244
TI - Effects of Secondary Plant Metabolites on Microbial Populations: Changes in
Community Structure and Metabolic Activity in Contaminated Environments.
AB - Secondary plant metabolites (SPMEs) play an important role in plant survival in
the environment and serve to establish ecological relationships between plants
and other organisms. Communication between plants and microorganisms via SPMEs
contained in root exudates or derived from litter decomposition is an example of
this phenomenon. In this review, the general aspects of rhizodeposition together
with the significance of terpenes and phenolic compounds are discussed in detail.
We focus specifically on the effect of SPMEs on microbial community structure and
metabolic activity in environments contaminated by polychlorinated biphenyls
(PCBs) and polyaromatic hydrocarbons (PAHs). Furthermore, a section is devoted to
a complex effect of plants and/or their metabolites contained in litter on
bioremediation of contaminated sites. New insights are introduced from a study
evaluating the effects of SPMEs derived during decomposition of grapefruit peel,
lemon peel, and pears on bacterial communities and their ability to degrade PCBs
in a long-term contaminated soil. The presented review supports the "secondary
compound hypothesis" and demonstrates the potential of SPMEs for increasing the
effectiveness of bioremediation processes.
PMID- 27483246
TI - The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty
Liver Disease and Cardiovascular Disease.
AB - The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity,
and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for
cardiovascular disease (CVD), has dramatically increased worldwide over the last
decades. Although dietary habit is the main etiologic factor, there is an
imperfect correlation between dietary habits and the development of metabolic
disease. Recently, research has focused on the role of the microbiome in the
development of these disorders. Indeed, gut microbiota is implicated in many
metabolic functions and an altered gut microbiota is reported in metabolic
disorders. Here we provide evidence linking gut microbiota and metabolic
diseases, focusing on the pathogenetic mechanisms underlying this association.
PMID- 27483247
TI - Genetic Mapping of a Major Resistance Gene to Pea Aphid (Acyrthosipon pisum) in
the Model Legume Medicago truncatula.
AB - Resistance to the Australian pea aphid (PA; Acyrthosiphon pisum) biotype in
cultivar Jester of the model legume Medicago truncatula is mediated by a single
dominant gene and is phloem-mediated. The genetic map position for this
resistance gene, APR (Acyrthosiphon pisum resistance), is provided and shows that
APR maps 39 centiMorgans (cM) distal of the A. kondoi resistance (AKR) locus,
which mediates resistance to a closely related species of the same genus
bluegreen aphid (A. kondoi). The APR region on chromosome 3 is dense in classical
nucleotide binding site leucine-rich repeats (NLRs) and overlaps with the region
harbouring the RAP1 gene which confers resistance to a European PA biotype in the
accession Jemalong A17. Further screening of a core collection of M. truncatula
accessions identified seven lines with strong resistance to PA. Allelism
experiments showed that the single dominant resistance to PA in M. truncatula
accessions SA10481 and SA1516 are allelic to SA10733, the donor of the APR locus
in cultivar Jester. While it remains unclear whether there are multiple PA
resistance genes in an R-gene cluster or the resistance loci identified in the
other M. truncatula accessions are allelic to APR, the introgression of APR into
current M. truncatula cultivars will provide more durable resistance to PA.
PMID- 27483248
TI - Association between IRS1 Gene Polymorphism and Autism Spectrum Disorder: A Pilot
Case-Control Study in Korean Males.
AB - The insulin-like growth factor (IGF) pathway is thought to play an important role
in brain development. Altered levels of IGFs and their signaling regulators have
been shown in autism spectrum disorder (ASD) patients. In this study, we
investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the
insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway,
were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and
rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD
patients and 147 male control subjects. A significant association between
rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) =
0.66, 95% confidence interval (CI) = 0.46-0.95) and dominant models (p = 0.013,
OR = 0.57, 95% CI = 0.37-0.89). Allele frequency analysis also showed an
association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46-0.94).
These results suggest that IRS1 may contribute to the susceptibility of ASD in
Korean males.
PMID- 27483249
TI - Peroxisome Proliferator-Activated Receptor gamma Expression Is Inversely
Associated with Macroscopic Vascular Invasion in Human Hepatocellular Carcinoma.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
activated nuclear receptor that regulates cellular lipid and glucose metabolism
and also plays an inhibitory role in various cancers. However, the role of
PPARgamma in hepatocellular carcinoma (HCC) remains controversial. This study
aimed to investigate the prognostic value of PPARgamma in HCC and its role in
inhibiting tumor progression, namely, HCC cell growth, migration, and
angiogenesis. Immunohistochemical PPARgamma staining was examined in 83 HCC
specimens to investigate the clinicopathological correlations between PPARgamma
expression and various parameters. The functional role of PPARgamma was
determined via PPARgamma overexpression and knockdown in HCC cells. Patients with
low HCC tissue PPARgamma expression were significantly younger (p = 0.006), and
exhibited more tumor numbers (p = 0.038), more macroscopic vascular invasion
(MVI) (p = 0.008), and more advanced TNM (size of primary tumor, number of
regional lymph nodes, and distant metastasis) stages at diagnosis (p = 0.013)
than patients with high HCC tissue PPARgamma expression. PPARgamma knockdown
increased HCC cell growth, migration, and angiogenesis, while PPARgamma
overexpression reduced HCC cell growth, migration, and angiogenesis. These
results suggest that low PPARgamma expression is an independent predictor of more
MVI in HCC patients. PPARgamma contributes to the suppression of HCC cell growth,
migration, and angiogenesis. Therefore, PPARgamma may be a therapeutic target in
HCC patients.
PMID- 27483250
TI - Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical
Orthogonal Arrays of Particles in Astrocytomas?
AB - The astrocytic endfoot membranes of the healthy blood-brain barrier-contacting
the capillary-are covered with a large number of the water channel aquaporin 4
(AQP4). They form orthogonal arrays of particles (OAPs), which consist of AQP4
isoform M1 and M23. Under pathologic conditions, AQP4 is distributed over the
whole cell and no or only small OAPs are found. From cell culture experiments, it
is known that cells transfected only with AQP4-M1 do not form OAPs or only small
ones. We hypothesized that in astrocytomas the situation may be comparable to the
in vitro experiments expecting an upregulation of AQP4-M1. Quantitative Real-time
PCR (qRT-PCR) of different graded astrocytomas revealed an upregulation of both
isoforms AQP4 M1 and M23 in all astrocytomas investigated. In freeze fracture
replicas of low-grade malignancy astrocytomas, more OAPs than in high-grade
malignancy astrocytomas were found. In vitro, cultured glioma cells did not
express AQP4, whereas healthy astrocytes revealed a slight upregulation of both
isoforms and only a few OAPs in freeze fracture analysis. Taken together, we
found a correlation between the decrease of OAPs and increasing grade of
malignancy of astrocytomas but this was not consistent with an upregulation of
AQP4-M1 in relation to AQP4 M23.
PMID- 27483252
TI - Correction: Yan Chen, et al. Dual Agent Loaded PLGA Nanoparticles Enhanced
Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model. Int. J.
Mol. Sci. 2014, 15, 2761-2772.
AB - Theauthorswishtomakeachangetotheirpublishedpaper[1].[...].
PMID- 27483251
TI - The Interactions of Aquaporins and Mineral Nutrients in Higher Plants.
AB - Aquaporins, major intrinsic proteins (MIPs) present in the plasma and
intracellular membranes, facilitate the transport of small neutral molecules
across cell membranes in higher plants. Recently, progress has been made in
understanding the mechanisms of aquaporin subcellular localization, transport
selectivity, and gating properties. Although the role of aquaporins in
maintaining the plant water status has been addressed, the interactions between
plant aquaporins and mineral nutrients remain largely unknown. This review
highlights the roles of various aquaporin orthologues in mineral nutrient uptake
and transport, as well as the regulatory effects of mineral nutrients on
aquaporin expression and activity, and an integrated link between aquaporins and
mineral nutrient metabolism was identified.
PMID- 27483253
TI - Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone
Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells.
AB - We examined the effects of the histone deacetylase inhibitor (HDACi)
suberoylanilide hydroxamic acid (SAHA) combined with the vascular endothelial
growth factor receptor-1/2 inhibitor (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)
2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast cancer cells (triple-negative) in
the form of both a cocktail of the separate compounds and a chemically
synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3
dihydro-1H-indol-5-yl]octanediamide). Comparative flow cytometric and Western
blot analyses were performed on cocktail- and hybrid-treated cells to evaluate
cell cycle distribution, autophagy/apoptosis modulation, and mitochondrial
metabolic state in order to understand the cellular basis of the cytotoxic
effect. Cell cycle analysis showed a perturbation of the rate of progression
through the cycle, with aspects of redistribution of cells over different cycle
phases for the two treatments. In addition, the results suggest that the two
distinct classes of compounds under investigation could induce cell death by
different preferential pathways, i.e., autophagy inhibition (the cocktail) or
apoptosis promotion (the hybrid), thus confirming the enhanced potential of the
hybrid approach vs. the combination approach in finely tuning the biological
activities of target cells and also showing the hybrid compound as an additional
promising drug-like molecule for the prevention or therapy of "aggressive" breast
carcinoma.
PMID- 27483254
TI - Urinary Dopamine as a Potential Index of the Transport Activity of Multidrug and
Toxin Extrusion in the Kidney.
AB - Dopamine is a cationic natriuretic catecholamine synthesized in proximal tubular
cells (PTCs) of the kidney before secretion into the lumen, a key site of its
action. However, the molecular mechanisms underlying dopamine secretion into the
lumen remain unclear. Multidrug and toxin extrusion (MATE) is a H+/organic cation
antiporter that is highly expressed in the brush border membrane of PTCs and
mediates the efflux of organic cations, including metformin and cisplatin, from
the epithelial cells into the urine. Therefore, we hypothesized that MATE
mediates dopamine secretion, a cationic catecholamine, into the tubule lumen,
thereby regulating natriuresis. Here, we show that [3H]dopamine uptake in human
(h) MATE1-, hMATE-2K- and mouse (m) MATE-expressing cells exhibited saturable
kinetics. Fluid retention and decreased urinary excretion of dopamine and Na+
were observed in Mate1-knockout mice compared to that in wild-type mice.
Imatinib, a MATE inhibitor, inhibited [3H]dopamine uptake by hMATE1-, hMATE2-K-
and mMATE1-expressing cells in a concentration-dependent manner. At clinically
relevant concentrations, imatinib inhibited [3H]dopamine uptake by hMATE1- and
hMATE2-K-expressing cells. The urinary excretion of dopamine and Na+ decreased
and fluid retention occurred in imatinib-treated mice. In conclusion, MATE
transporters secrete renally-synthesized dopamine, and therefore, urinary
dopamine has the potential to be an index of the MATE transporter activity.
PMID- 27483255
TI - Navicula sp. Sulfated Polysaccharide Gels Induced by Fe(III): Rheology and
Microstructure.
AB - A sulfated polysaccharide extracted from Navicula sp. presented a yield of 4.4 (%
w/w dry biomass basis). Analysis of the polysaccharide using gas chromatography
showed that this polysaccharide contained glucose (29%), galactose (21%),
rhamnose (10%), xylose (5%) and mannose (4%). This polysaccharide presented an
average molecular weight of 107 kDa. Scanning electron microscopy (SEM)
micrographs showed that the lyophilized Navicula sp. polysaccharide is an
amorphous solid with particles of irregular shapes and sharp angles. The
polysaccharide at 1% (w/v) solution in water formed gels in the presence of 0.4%
(w/v) FeCl3, showing elastic and viscous moduli of 1 and 0.7 Pa, respectively.
SEM analysis performed on the lyophilized gel showed a compact pore structure,
with a pore size of approximately 150 nm. Very few studies on the gelation of
sulfated polysaccharides using trivalent ions exist in the literature, and, to
the best of our knowledge, this study is the first to describe the gelation of
sulfated polysaccharides extracted from Navicula sp.
PMID- 27483256
TI - VEGF and FGF2 Improve Revascularization, Survival, and Oocyte Quality of
Cryopreserved, Subcutaneously-Transplanted Mouse Ovarian Tissues.
AB - This study was conducted to investigate the effect of the vascular endothelial
growth factor (VEGF) and fibroblast growth factor 2 (FGF2) on revascularization,
survival, and oocyte quality of cryopreserved, subcutaneously-transplanted mouse
ovarian tissue. Autologous subcutaneous transplantation of vitrified-thawed mouse
ovarian tissues treated with (experimental group) or without (control group) VEGF
and FGF2 was performed. After transplantation to the inguinal region for two or
three weeks, graft survival, angiogenesis, follicle development, and oocyte
quality were examined after gonadotropin administration. VEGF coupled with FGF2
(VEGF/FGF2) promoted revascularization and significantly increased the survival
rate of subcutaneously-transplanted cryopreserved ovarian tissues compared with
untreated controls. The two growth factors did not show long-term effects on the
ovarian grafts. In contrast to the untreated ovarian grafts, active
folliculogenesis was revealed as the number of follicles at various stages and of
mature oocytes in antral follicles after gonadotropin administration were
remarkably higher in the VEGF/FGF2-treated groups. Although the fertilization
rate was similar between the VEGF/FGF2 and control groups, the oocyte quality was
much better in the VEGF/FGF2-treated grafts as demonstrated by the higher ratio
of blastocyst development. Introducing angiogenic factors, such as VEGF and FGF2,
may be a promising strategy to improve revascularization, survival, and oocyte
quality of cryopreserved, subcutaneously-transplanted mouse ovarian tissue.
PMID- 27483257
TI - SMA Human iPSC-Derived Motor Neurons Show Perturbed Differentiation and Reduced
miR-335-5p Expression.
AB - Spinal Muscular Atrophy (SMA) is a neuromuscular disease caused by mutations in
the Survival Motor Neuron 1 gene, resulting in very low levels of functional
Survival of Motor Neuron (SMN) protein. SMA human induced Pluripotent Stem Cells
(hiPSCs) represent a useful and valid model for the study of the disorder, as
they provide in vitro the target cells. MicroRNAs (miRNAs) are often reported as
playing a key role in regulating neuronal differentiation and fate specification.
In this study SMA hiPSCs have been differentiated towards early motor neurons and
their molecular and immunocytochemical profile were compared to those of wild
type cells. Cell cycle proliferation was also evaluated by fluorescence-activated
cell sorting (FACS). SMA hiPSCs showed an increased proliferation rate and also
higher levels of stem cell markers. Moreover; when differentiated towards early
motor neurons they expressed lower levels of NCAM and MN specific markers. The
expression of miR-335-5p; already identified to control self-renewal or
differentiation of mouse embryonic stem cells (mESCs); resulted to be reduced
during the early steps of differentiation of SMA hiPSCs compared to wild type
cells. These results suggest that we should speculate a role of this miRNA both
in stemness characteristic and in differentiation efficiency of these cells.
PMID- 27483260
TI - A Next-Generation Sequencing Approach to Identify Gene Mutations in Early- and
Late-Onset Hypertrophic Cardiomyopathy Patients of an Italian Cohort.
AB - Sequencing of sarcomere protein genes in patients fulfilling the clinical
diagnostic criteria for hypertrophic cardiomyopathy (HCM) identifies a disease
causing mutation in 35% to 60% of cases. Age at diagnosis and family history may
increase the yield of mutations screening. In order to assess whether Next
Generation Sequencing (NGS) may fulfil the molecular diagnostic needs in HCM, we
included 17 HCM-related genes in a sequencing panel run on PGM IonTorrent. We
selected 70 HCM patients, 35 with early (<=25 years) and 35 with late (>=65
years) diagnosis of disease onset. All samples had a 98.6% average of target
regions, with coverage higher than 20* (mean coverage 620*). We identified 41
different mutations (seven of them novel) in nine genes: MYBPC3 (17/41 = 41%);
MYH7 (10/41 = 24%); TNNT2, CAV3 and MYH6 (3/41 = 7.5% each); TNNI3 (2/41 = 5%);
GLA, MYL2, and MYL3 (1/41=2.5% each). Mutation detection rate was 30/35 (85.7%)
in early-onset and 8/35 (22.9%) in late-onset HCM patients, respectively (p <
0.0001). The overall detection rate for patients with positive family history was
84%, and 90.5% in patients with early disease onset. In our study NGS revealed
higher mutations yield in patients with early onset and with a family history of
HCM. Appropriate patient selection can increase the yield of genetic testing and
make diagnostic testing cost-effective.
PMID- 27483259
TI - Is the Mouse a Good Model of Human PPARgamma-Related Metabolic Diseases?
AB - With the increasing number of patients affected with metabolic diseases such as
type 2 diabetes, obesity, atherosclerosis and insulin resistance, academic
researchers and pharmaceutical companies are eager to better understand metabolic
syndrome and develop new drugs for its treatment. Many studies have focused on
the nuclear receptor peroxisome proliferator-activated receptor gamma
(PPARgamma), which plays a crucial role in adipogenesis and lipid metabolism.
These studies have been able to connect this transcription factor to several
human metabolic diseases. Due to obvious limitations concerning experimentation
in humans, animal models-mainly mouse models-have been generated to investigate
the role of PPARgamma in different tissues. This review focuses on the metabolic
features of human and mouse PPARgamma-related diseases and the utility of the
mouse as a model.
PMID- 27483261
TI - Time-Varying Vocal Folds Vibration Detection Using a 24 GHz Portable Auditory
Radar.
AB - Time-varying vocal folds vibration information is of crucial importance in speech
processing, and the traditional devices to acquire speech signals are easily
smeared by the high background noise and voice interference. In this paper, we
present a non-acoustic way to capture the human vocal folds vibration using a 24
GHz portable auditory radar. Since the vocal folds vibration only reaches several
millimeters, the high operating frequency and the 4 * 4 array antennas are
applied to achieve the high sensitivity. The Variational Mode Decomposition (VMD)
based algorithm is proposed to decompose the radar-detected auditory signal into
a sequence of intrinsic modes firstly, and then, extract the time-varying vocal
folds vibration frequency from the corresponding mode. Feasibility demonstration,
evaluation, and comparison are conducted with tonal and non-tonal languages, and
the low relative errors show a high consistency between the radar-detected
auditory time-varying vocal folds vibration and acoustic fundamental frequency,
except that the auditory radar significantly improves the frequency-resolving
power.
PMID- 27483258
TI - Molecular Mechanisms of Cutaneous Inflammatory Disorder: Atopic Dermatitis.
AB - Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting
from interactions between genetic susceptibility and environmental factors. The
pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is
still challenging. There is accumulating evidence for new gene polymorphisms
related to the epidermal barrier function and innate and adaptive immunity in
patients with AD. Newly-found T cells and dendritic cell subsets, cytokines,
chemokines and signaling pathways have extended our understanding of the
molecular pathomechanism underlying AD. Genetic changes caused by environmental
factors have been shown to contribute to the pathogenesis of AD. We herein
present a review of the genetics, epigenetics, barrier dysfunction and
immunological abnormalities in AD with a focus on updated molecular biology.
PMID- 27483262
TI - Three-Dimensional Photon Counting Imaging with Axially Distributed Sensing.
AB - In this paper, we review three-dimensional (3D) photon counting imaging with
axially distributed sensing. Under severely photon-starved conditions, we have
proposed various imaging and algorithmic approaches to reconstruct a scene in 3D,
which are not possible by using conventional imaging system due to lack of
sufficient number of photons. In this paper, we present an overview of optical
sensing and imaging system along with dedicated algorithms for reconstructing 3D
scenes by photon counting axially distributed sensing, which may be implemented
by moving a single image sensor along its optical axis. To visualize the 3D
image, statistical estimation methods and computational reconstruction of axially
distributed sensing is applied.
PMID- 27483263
TI - Monolithic Cylindrical Fused Silica Resonators with High Q Factors.
AB - The cylindrical resonator gyroscope (CRG) is a typical Coriolis vibratory
gyroscope whose performance is determined by the Q factor and frequency mismatch
of the cylindrical resonator. Enhancing the Q factor is crucial for improving the
rate sensitivity and noise performance of the CRG. In this paper, for the first
time, a monolithic cylindrical fused silica resonator with a Q factor approaching
8 * 105 (ring-down time over 1 min) is reported. The resonator is made of fused
silica with low internal friction and high isotropy, with a diameter of 25 mm and
a center frequency of 3974.35 Hz. The structure of the resonator is first briefly
introduced, and then the experimental non-contact characterization method is
presented. In addition, the post-fabrication experimental procedure of Q factor
improvement, including chemical and thermal treatment, is demonstrated. The Q
factor improvement by both treatments is compared and the primary loss mechanism
is analyzed. To the best of our knowledge, the work presented in this paper
represents the highest reported Q factor for a cylindrical resonator. The
proposed monolithic cylindrical fused silica resonator may enable high
performance inertial sensing with standard manufacturing process and simple post
fabrication treatment.
PMID- 27483264
TI - Object Detection Applied to Indoor Environments for Mobile Robot Navigation.
AB - To move around the environment, human beings depend on sight more than their
other senses, because it provides information about the size, shape, color and
position of an object. The increasing interest in building autonomous mobile
systems makes the detection and recognition of objects in indoor environments a
very important and challenging task. In this work, a vision system to detect
objects considering usual human environments, able to work on a real mobile
robot, is developed. In the proposed system, the classification method used is
Support Vector Machine (SVM) and as input to this system, RGB and depth images
are used. Different segmentation techniques have been applied to each kind of
object. Similarly, two alternatives to extract features of the objects are
explored, based on geometric shape descriptors and bag of words. The experimental
results have demonstrated the usefulness of the system for the detection and
location of the objects in indoor environments. Furthermore, through the
comparison of two proposed methods for extracting features, it has been
determined which alternative offers better performance. The final results have
been obtained taking into account the proposed problem and that the environment
has not been changed, that is to say, the environment has not been altered to
perform the tests.
PMID- 27483265
TI - Fast Object Motion Estimation Based on Dynamic Stixels.
AB - The stixel world is a simplification of the world in which obstacles are
represented as vertical instances, called stixels, standing on a surface assumed
to be planar. In this paper, previous approaches for stixel tracking are extended
using a two-level scheme. In the first level, stixels are tracked by matching
them between frames using a bipartite graph in which edges represent a matching
cost function. Then, stixels are clustered into sets representing objects in the
environment. These objects are matched based on the number of stixels paired
inside them. Furthermore, a faster, but less accurate approach is proposed in
which only the second level is used. Several configurations of our method are
compared to an existing state-of-the-art approach to show how our methodology
outperforms it in several areas, including an improvement in the quality of the
depth reconstruction.
PMID- 27483266
TI - Practical Application of Electrochemical Nitrate Sensor under Laboratory and
Forest Nursery Conditions.
AB - The reduction of nitrate leaching to ensure greater protection of groundwater
quality has become a global issue. The development of new technologies for more
accurate dosing of nitrates helps optimize fertilization programs. This paper
presents the practical application of a newly developed electrochemical sensor
designed for in situ quantification of nitrate. To our knowledge, this paper is
the first to report the use of electrochemical impedance to determine nitrate
concentrations in growing media under forest nursery conditions. Using impedance
measurements, the sensor has been tested in laboratory and compared to
colorimetric measurements of the nitrate. The developed sensor has been used in
water-saturated growing medium and showed good correlation to certified methods,
even in samples obtained over a multi-ion fertilisation season. A linear and
significant relationship was observed between the resistance and the
concentration of nitrates (R2 = 0.972), for a range of concentrations of
nitrates. We also observed stability of the sensor after exposure of one month to
the real environmental conditions of the forest nursery.
PMID- 27483267
TI - A Robust Distributed Multipoint Fiber Optic Gas Sensor System Based on AGC
Amplifier Structure.
AB - A harsh environment-oriented distributed multipoint fiber optic gas sensor system
realized by automatic gain control (AGC) technology is proposed. To improve the
photoelectric signal reliability, the electronic variable gain can be modified in
real time by an AGC closed-loop feedback structure to compensate for optical
transmission loss which is caused by the fiber bend loss or other reasons. The
deviation of the system based on AGC structure is below 4.02% when photoelectric
signal decays due to fiber bending loss for bending radius of 5 mm, which is 20
times lower than the ordinary differential system. In addition, the AGC circuit
with the same electric parameters can keep the baseline intensity of signals in
different channels of the distributed multipoint sensor system at the same level.
This avoids repetitive calibrations and streamlines the installation process.
PMID- 27483268
TI - Micromechanical Characterization of Polysilicon Films through On-Chip Tests.
AB - When the dimensions of polycrystalline structures become comparable to the
average grain size, some reliability issues can be reported for the moving parts
of inertial microelectromechanical systems (MEMS). Not only the overall behavior
of the device turns out to be affected by a large scattering, but also the
sensitivity to imperfections gets enhanced. In this work, through on-chip tests,
we experimentally investigate the behavior of thin polysilicon samples using
standard electrostatic actuation/sensing. The discrepancy between the target and
actual responses of each sample has then been exploited to identify: (i) the
overall stiffness of the film and, according to standard continuum elasticity, a
morphology-based value of its Young's modulus; (ii) the relevant over-etch
induced by the fabrication process. To properly account for the aforementioned
stochastic features at the micro-scale, the identification procedure has been
based on particle filtering. A simple analytical reduced-order model of the
moving structure has been also developed to account for the nonlinearities in the
electrical field, up to pull-in. Results are reported for a set of ten film
samples of constant slenderness, and the effects of different actuation
mechanisms on the identified micromechanical features are thoroughly discussed.
PMID- 27483269
TI - Safety and Traceability in Patient Healthcare through the Integration of RFID
Technology for Intravenous Mixtures in the Prescription-Validation-Elaboration
Dispensation-Administration Circuit to Day Hospital Patients.
AB - This work presents the integration of the RFID technology with the aim of
ensuring the traceability of patients and minimization of adverse events during
the process of prescription-validation-elaboration-dispensation-administration of
medication by means of the implementation of various passive and active WIFI RFID
systems in the Pharmacy and Day Hospital services of the Complejo Hospitalario
Universitario A Coruna. Obtaining patient traceability and using the patient/drug
binomial during this process allows us to minimize the occurrence of adverse
events. The key points in this work are the unmistakably unique identification
and accurate real time location of the controlled items (patients and
medication). RFID technology has proved to be invaluable in assisting with the
everyday clinical practice of a hospital, and has been successfully implemented
in this environment and others. In services such as the day hospital, the
implementation of said technology is further justified by the high costs of the
service and the high risk to the patient.
PMID- 27483270
TI - A Long-Term Performance Enhancement Method for FOG-Based Measurement While
Drilling.
AB - In the oil industry, the measurement-while-drilling (MWD) systems are usually
used to provide the real-time position and orientation of the bottom hole
assembly (BHA) during drilling. However, the present MWD systems based on
magnetic surveying technology can barely ensure good performance because of
magnetic interference phenomena. In this paper, a MWD surveying system based on a
fiber optic gyroscope (FOG) was developed to replace the magnetic surveying
system. To accommodate the size of the downhole drilling conditions, a new design
method is adopted. In order to realize long-term and high position precision and
orientation surveying, an integrated surveying algorithm is proposed based on
inertial navigation system (INS) and drilling features. In addition, the FOG
based MWD error model is built and the drilling features are analyzed. The state
space system model and the observation updates model of the Kalman filter are
built. To validate the availability and utility of the algorithm, the semi
physical simulation is conducted under laboratory conditions. The results
comparison with the traditional algorithms show that the errors were suppressed
and the measurement precision of the proposed algorithm is better than the
traditional ones. In addition, the proposed method uses a lot less time than the
zero velocity update (ZUPT) method.
PMID- 27483271
TI - Fiber-Optic Surface Temperature Sensor Based on Modal Interference.
AB - Spatially-integrated surface temperature sensing is highly useful when it comes
to controlling processes, detecting hazardous conditions or monitoring the health
and safety of equipment and people. Fiber-optic sensing based on modal
interference has shown great sensitivity to temperature variation, by means of
cost-effective image-processing of few-mode interference patterns. New
developments in the field of sensor configuration, as described in this paper,
include an innovative cooling and heating phase discrimination functionality and
more precise measurements, based entirely on the image processing of interference
patterns. The proposed technique was applied to the measurement of the integrated
surface temperature of a hollow cylinder and compared with a conventional
measurement system, consisting of an infrared camera and precision temperature
probe. As a result, the optical technique is in line with the reference system.
Compared with conventional surface temperature probes, the optical technique has
the following advantages: low heat capacity temperature measurement errors,
easier spatial deployment, and replacement of multiple angle infrared camera
shooting and the continuous monitoring of surfaces that are not visually
accessible.
PMID- 27483272
TI - Eigenspace-Based Generalized Sidelobe Canceler Beamforming Applied to Medical
Ultrasound Imaging.
AB - The use of a generalized sidelobe canceler (GSC) can significantly improve the
lateral resolution of medical ultrasound systems, but the contrast improvement
isn't satisfactory. Thus a new Eigenspace-based generalized sidelobe canceler
(EBGSC) approach is proposed for medical ultrasound imaging, which can improve
both the lateral resolution and contrast of the system. The weight vector of the
EBGSC is obtained by projecting the GSC weight vector onto a vector subspace
constructed from the eigenstructure of the covariance matrix, and using the new
weight vector instead of the GSC ones leads to reduced sidelobe level and
improved contrast. Simulated and experimental data are used to evaluate the
performance of the proposed method. The Field II software is applied to obtain
the simulated echo data of scattering points and circular cysts. Imaging of
scattering points show that EBGSC has the same full width at half maximum (FWHM)
as GSC, while the lateral resolution improves by 35.3% and 52.7% compared with
synthetic aperture (SA) and delay-and-sum (DS), respectively. Compared with GSC,
SA and DS, EBGSC improves the peak sidelobe level (PSL) by 23.55, 33.11 and 50.38
dB, respectively. Also the cyst contrast increase by EBGSC was calculated as
16.77, 12.43 and 26.73 dB, when compared with GSC, SA and DS, respectively.
Finally, an experiment is conducted on the basis of the complete echo data
collected by a medical ultrasonic imaging system. Results show that the proposed
method can produce better lateral resolution and contrast than non-adaptive
beamformers.
PMID- 27483273
TI - Exact Distributions of Finite Random Matrices and Their Applications to Spectrum
Sensing.
AB - The exact and simple distributions of finite random matrix theory (FRMT) are
critically important for cognitive radio networks (CRNs). In this paper, we unify
some existing distributions of the FRMT with the proposed coefficient matrices
(vectors) and represent the distributions with the coefficient-based
formulations. A coefficient reuse mechanism is studied, i.e., the same
coefficient matrices (vectors) can be exploited to formulate different
distributions. For instance, the same coefficient matrices can be used by the
largest eigenvalue (LE) and the scaled largest eigenvalue (SLE); the same
coefficient vectors can be used by the smallest eigenvalue (SE) and the Demmel
condition number (DCN). A new and simple cumulative distribution function (CDF)
of the DCN is also deduced. In particular, the dimension boundary between the
infinite random matrix theory (IRMT) and the FRMT is initially defined. The
dimension boundary provides a theoretical way to divide random matrices into
infinite random matrices and finite random matrices. The FRMT-based spectrum
sensing (SS) schemes are studied for CRNs. The SLE-based scheme can be considered
as an asymptotically-optimal SS scheme when the dimension K is larger than two.
Moreover, the standard condition number (SCN)-based scheme achieves the same
sensing performance as the SLE-based scheme for dual covariance matrix K = 2 .
The simulation results verify that the coefficient-based distributions can fit
the empirical results very well, and the FRMT-based schemes outperform the IRMT
based schemes and the conventional SS schemes.
PMID- 27483274
TI - Applying High-Speed Vision Sensing to an Industrial Robot for High-Performance
Position Regulation under Uncertainties.
AB - It is traditionally difficult to implement fast and accurate position regulation
on an industrial robot in the presence of uncertainties. The uncertain factors
can be attributed either to the industrial robot itself (e.g., a mismatch of
dynamics, mechanical defects such as backlash, etc.) or to the external
environment (e.g., calibration errors, misalignment or perturbations of a
workpiece, etc.). This paper proposes a systematic approach to implement high
performance position regulation under uncertainties on a general industrial robot
(referred to as the main robot) with minimal or no manual teaching. The method is
based on a coarse-to-fine strategy that involves configuring an add-on module for
the main robot's end effector. The add-on module consists of a 1000 Hz vision
sensor and a high-speed actuator to compensate for accumulated uncertainties. The
main robot only focuses on fast and coarse motion, with its trajectories
automatically planned by image information from a static low-cost camera. Fast
and accurate peg-and-hole alignment in one dimension was implemented as an
application scenario by using a commercial parallel-link robot and an add-on
compensation module with one degree of freedom (DoF). Experimental results
yielded an almost 100% success rate for fast peg-in-hole manipulation (with
regulation accuracy at about 0.1 mm) when the workpiece was randomly placed.
PMID- 27483275
TI - A Design Method of Code Correlation Reference Waveform in GNSS Based on Least
Squares Fitting.
AB - The multipath effect is one of the main error sources in the Global Satellite
Navigation Systems (GNSSs). The code correlation reference waveform (CCRW)
technique is an effective multipath mitigation algorithm for the binary phase
shift keying (BPSK) signal. However, it encounters the false lock problem in code
tracking, when applied to the binary offset carrier (BOC) signals. A least
squares approximation method of the CCRW design scheme is proposed, utilizing the
truncated singular value decomposition method. This algorithm was performed for
the BPSK signal, BOC(1,1) signal, BOC(2,1) signal, BOC(6,1) and BOC(7,1) signal.
The approximation results of CCRWs were presented. Furthermore, the performances
of the approximation results are analyzed in terms of the multipath error
envelope and the tracking jitter. The results show that the proposed method can
realize coherent and non-coherent CCRW discriminators without false lock points.
Generally, there is performance degradation in the tracking jitter, if compared
to the CCRW discriminator. However, the performance promotions in the multipath
error envelope for the BOC(1,1) and BPSK signals makes the discriminator
attractive, and it can be applied to high-order BOC signals.
PMID- 27483276
TI - Gaussian Process Regression Plus Method for Localization Reliability Improvement.
AB - Location data are among the most widely used context data in context-aware and
ubiquitous computing applications. Many systems with distinct deployment costs
and positioning accuracies have been developed over the past decade for indoor
positioning. The most useful method is focused on the received signal strength
and provides a set of signal transmission access points. However, compiling a
manual measuring Received Signal Strength (RSS) fingerprint database involves
high costs and thus is impractical in an online prediction environment. The
system used in this study relied on the Gaussian process method, which is a
nonparametric model that can be characterized completely by using the mean
function and the covariance matrix. In addition, the Naive Bayes method was used
to verify and simplify the computation of precise predictions. The authors
conducted several experiments on simulated and real environments at Tianjin
University. The experiments examined distinct data size, different kernels, and
accuracy. The results showed that the proposed method not only can retain
positioning accuracy but also can save computation time in location predictions.
PMID- 27483277
TI - Integrating a DNA Strand Displacement Reaction with a Whispering Gallery Mode
Sensor for Label-Free Mercury (II) Ion Detection.
AB - Mercury is an extremely toxic chemical pollutant of our environment. It has
attracted the world's attention due to its high mobility and the ease with which
it accumulates in organisms. Sensitive devices and methods specific for detecting
mercury ions are, hence, in great need. Here, we have integrated a DNA strand
displacement reaction with a whispering gallery mode (WGM) sensor for
demonstrating the detection of Hg(2+) ions. Our approach relies on the
displacement of a DNA hairpin structure, which forms after the binding of mercury
ions to an aptamer DNA sequence. The strand displacement reaction of the DNA
aptamer provides highly specific and quantitative means for determining the
mercury ion concentration on a label-free WGM sensor platform. Our approach also
shows the possibility for manipulating the kinetics of a strand displacement
reaction with specific ionic species.
PMID- 27483278
TI - A Novel Single-Excitation Capacitive Angular Position Sensor Design.
AB - This paper presents a high-precision capacitive angular position sensor (CAPS).
The CAPS is designed to be excited by a single voltage to eliminate the matching
errors of multi-excitations, and it is mainly composed of excitation electrodes,
coupling electrodes, petal-form sensitive electrodes and a set of collection
electrodes. A sinusoidal voltage is applied on the excitation electrodes, then
the voltage couples to the coupling electrodes and sensitive electrodes without
contact. The sensitive electrodes together with the set of collection electrodes
encode the angular position to amplitude-modulated signals, and in order to
increase the scale factor, the sensitive electrodes are patterned in the shape of
petal-form sinusoidal circles. By utilizing a resolver demodulation method, the
amplitude-modulated signals are digitally decoded to get the angular position. A
prototype of the CAPS is fabricated and tested. The measurement results show that
the accuracy of the sensor is 0.0036 degrees , the resolution is 0.0009 degrees
and the nonlinearity over the full range is 0.008 degrees (after compensation),
indicating that the CAPS has great potential to be applied in high-precision
applications with a low cost.
PMID- 27483279
TI - Design of an HF-Band RFID System with Multiple Readers and Passive Tags for
Indoor Mobile Robot Self-Localization.
AB - Radio frequency identification (RFID) technology has already been explored for
efficient self-localization of indoor mobile robots. A mobile robot equipped with
RFID readers detects passive RFID tags installed on the floor in order to locate
itself. The Monte-Carlo localization (MCL) method enables the localization of a
mobile robot equipped with an RFID system with reasonable accuracy, sufficient
robustness and low computational cost. The arrangements of RFID readers and tags
and the size of antennas are important design parameters for realizing accurate
and robust self-localization using a low-cost RFID system. The design of a
likelihood model of RFID tag detection is also crucial for the accurate self
localization. This paper presents a novel design and arrangement of RFID readers
and tags for indoor mobile robot self-localization. First, by considering small
sized and large-sized antennas of an RFID reader, we show how the design of the
likelihood model affects the accuracy of self-localization. We also design a
novel likelihood model by taking into consideration the characteristics of the
communication range of an RFID system with a large antenna. Second, we propose a
novel arrangement of RFID tags with eight RFID readers, which results in the RFID
system configuration requiring much fewer readers and tags while retaining
reasonable accuracy of self-localization. We verify the performances of MCL-based
self-localization realized using the high-frequency (HF)-band RFID system with
eight RFID readers and a lower density of RFID tags installed on the floor based
on MCL in simulated and real environments. The results of simulations and real
environment experiments demonstrate that our proposed low-cost HF-band RFID
system realizes accurate and robust self-localization of an indoor mobile robot.
PMID- 27483280
TI - Development of a Distributed Crack Sensor Using Coaxial Cable.
AB - Cracks, the important factor of structure failure, reflect structural damage
directly. Thus, it is significant to realize distributed, real-time crack
monitoring. To overcome the shortages of traditional crack detectors, such as the
inconvenience of installation, vulnerability, and low measurement range, etc., an
improved topology-based cable sensor with a shallow helical groove on the outside
surface of a coaxial cable is proposed in this paper. The sensing mechanism,
fabrication method, and performances are investigated both numerically and
experimentally. Crack monitoring experiments of the reinforced beams are also
presented in this paper, illustrating the utility of this sensor in practical
applications. These studies show that the sensor can identify a minimum crack
width of 0.02 mm and can measure multiple cracks with a spatial resolution of 3
mm. In addition, it is also proved that the sensor performs well to detect the
initiation and development of cracks until structure failure.
PMID- 27483282
TI - Maximum Data Collection Rate Routing Protocol Based on Topology Control for
Rechargeable Wireless Sensor Networks.
AB - In Rechargeable Wireless Sensor Networks (R-WSNs), in order to achieve the
maximum data collection rate it is critical that sensors operate in very low duty
cycles because of the sporadic availability of energy. A sensor has to stay in a
dormant state in most of the time in order to recharge the battery and use the
energy prudently. In addition, a sensor cannot always conserve energy if a
network is able to harvest excessive energy from the environment due to its
limited storage capacity. Therefore, energy exploitation and energy saving have
to be traded off depending on distinct application scenarios. Since higher data
collection rate or maximum data collection rate is the ultimate objective for
sensor deployment, surplus energy of a node can be utilized for strengthening
packet delivery efficiency and improving the data generating rate in R-WSNs. In
this work, we propose an algorithm based on data aggregation to compute an upper
data generation rate by maximizing it as an optimization problem for a network,
which is formulated as a linear programming problem. Subsequently, a dual problem
by introducing Lagrange multipliers is constructed, and subgradient algorithms
are used to solve it in a distributed manner. At the same time, a topology
controlling scheme is adopted for improving the network's performance. Through
extensive simulation and experiments, we demonstrate that our algorithm is
efficient at maximizing the data collection rate in rechargeable wireless sensor
networks.
PMID- 27483281
TI - A Portable Real-Time Ringdown Breath Acetone Analyzer: Toward Potential Diabetic
Screening and Management.
AB - Breath analysis has been considered a suitable tool to evaluate diseases of the
respiratory system and those that involve metabolic changes, such as diabetes.
Breath acetone has long been known as a biomarker for diabetes. However, the
results from published data by far have been inconclusive regarding whether
breath acetone is a reliable index of diabetic screening. Large variations exist
among the results of different studies because there has been no "best-practice
method" for breath-acetone measurements as a result of technical problems of
sampling and analysis. In this mini-review, we update the current status of our
development of a laser-based breath acetone analyzer toward real-time, one-line
diabetic screening and a point-of-care instrument for diabetic management. An
integrated standalone breath acetone analyzer based on the cavity ringdown
spectroscopy technique has been developed. The instrument was validated by using
the certificated gas chromatography-mass spectrometry. The linear fittings
suggest that the obtained acetone concentrations via both methods are consistent.
Breath samples from each individual subject under various conditions in total,
1257 breath samples were taken from 22 Type 1 diabetic (T1D) patients, 312 Type 2
diabetic (T2D) patients, which is one of the largest numbers of T2D subjects ever
used in a single study, and 52 non-diabetic healthy subjects. Simultaneous blood
glucose (BG) levels were also tested using a standard diabetic management BG
meter. The mean breath acetone concentrations were determined to be 4.9 +/- 16
ppm (22 T1D), and 1.5 +/- 1.3 ppm (312 T2D), which are about 4.5 and 1.4 times of
the one in the 42 non-diabetic healthy subjects, 1.1 +/- 0.5 ppm, respectively. A
preliminary quantitative correlation (R = 0.56, p < 0.05) between the mean
individual breath acetone concentration and the mean individual BG levels does
exist in 20 T1D subjects with no ketoacidosis. No direct correlation is observed
in T1D subjects, T2D subjects, and healthy subjects. The results from a
relatively large number of subjects tested indicate that an elevated mean breath
acetone concentration exists in diabetic patients in general. Although many
physiological parameters affect breath acetone, under a specifically controlled
condition fast (<1 min) and portable breath acetone measurement can be used for
screening abnormal metabolic status including diabetes, for point-of-care
monitoring status of ketone bodies which have the signature smell of breath
acetone, and for breath acetone related clinical studies requiring a large number
of tests.
PMID- 27483283
TI - Dynamic Calibration and Verification Device of Measurement System for Dynamic
Characteristic Coefficients of Sliding Bearing.
AB - The identification accuracy of dynamic characteristics coefficients is difficult
to guarantee because of the errors of the measurement system itself. A novel
dynamic calibration method of measurement system for dynamic characteristics
coefficients is proposed in this paper to eliminate the errors of the measurement
system itself. Compared with the calibration method of suspension quality, this
novel calibration method is different because the verification device is a spring
mass system, which can simulate the dynamic characteristics of sliding bearing.
The verification device is built, and the calibration experiment is implemented
in a wide frequency range, in which the bearing stiffness is simulated by the
disc springs. The experimental results show that the amplitude errors of this
measurement system are small in the frequency range of 10 Hz-100 Hz, and the
phase errors increase along with the increasing of frequency. It is preliminarily
verified by the simulated experiment of dynamic characteristics coefficients
identification in the frequency range of 10 Hz-30 Hz that the calibration data in
this frequency range can support the dynamic characteristics test of sliding
bearing in this frequency range well. The bearing experiments in greater
frequency ranges need higher manufacturing and installation precision of
calibration device. Besides, the processes of calibration experiments should be
improved.
PMID- 27483284
TI - Analysis on Node Position of Imperfect Resonators for Cylindrical Shell
Gyroscopes.
AB - For cylindrical shell gyroscopes, node position of their operating eigenmodes has
an important influence on the gyroscopes' performance. It is considered that the
nodes are equally separated from each other by 90 degrees when the resonator
vibrates in the standing wave eigenmode. However, we found that, due to
manufacturing errors and trimming, the nodes may not be equally distributed. This
paper mainly analyzes the influences of unbalanced masses on the cylindrical
resonators' node position, by using FEM simulation and experimental measurement.
PMID- 27483285
TI - Genetic Particle Swarm Optimization-Based Feature Selection for Very-High
Resolution Remotely Sensed Imagery Object Change Detection.
AB - In the field of multiple features Object-Based Change Detection (OBCD) for very
high-resolution remotely sensed images, image objects have abundant features and
feature selection affects the precision and efficiency of OBCD. Through object
based image analysis, this paper proposes a Genetic Particle Swarm Optimization
(GPSO)-based feature selection algorithm to solve the optimization problem of
feature selection in multiple features OBCD. We select the Ratio of Mean to
Variance (RMV) as the fitness function of GPSO, and apply the proposed algorithm
to the object-based hybrid multivariate alternative detection model. Two
experiment cases on Worldview-2/3 images confirm that GPSO can significantly
improve the speed of convergence, and effectively avoid the problem of premature
convergence, relative to other feature selection algorithms. According to the
accuracy evaluation of OBCD, GPSO is superior at overall accuracy (84.17% and
83.59%) and Kappa coefficient (0.6771 and 0.6314) than other algorithms.
Moreover, the sensitivity analysis results show that the proposed algorithm is
not easily influenced by the initial parameters, but the number of features to be
selected and the size of the particle swarm would affect the algorithm. The
comparison experiment results reveal that RMV is more suitable than other
functions as the fitness function of GPSO-based feature selection algorithm.
PMID- 27483286
TI - Modeling and Experimental Analysis on the Temperature Response of AlN-Film Based
SAWRs.
AB - The temperature responses of aluminum nitride (AlN) based surface acoustic wave
resonator (SAWR) are modeled and tested. The modeling of the electrical
performance is based on a modified equivalent circuit model introduced in this
work. For SAWR consisting of piezoelectric film and semiconducting substrate,
parasitic parameters from the substrate is taken into consideration for the
modeling. By utilizing the modified model, the high temperature electrical
performance of the AlN/Si and AlN/6H-SiC based SAWRs can be predicted, indicating
that a substrate with a wider band gap will lead to a more stable high
temperature behavior, which is further confirmed experimentally by high
temperature testing from 300 K to 725 K with SAWRs having a wavelength of 12 MUm.
Temperature responses of SAWR's center frequency are also calculated and tested,
with experimental temperature coefficient factors (TCF) of center frequency being
-29 ppm/K and -26 ppm/K for the AlN/Si and AlN/6H-SiC based SAWRs, which are
close to the predicted values.
PMID- 27483287
TI - On-Ground Processing of Yaogan-24 Remote Sensing Satellite Attitude Data and
Verification Using Geometric Field Calibration.
AB - Satellite attitude accuracy is an important factor affecting the geometric
processing accuracy of high-resolution optical satellite imagery. To address the
problem whereby the accuracy of the Yaogan-24 remote sensing satellite's on-board
attitude data processing is not high enough and thus cannot meet its image
geometry processing requirements, we developed an approach involving on-ground
attitude data processing and digital orthophoto (DOM) and the digital elevation
model (DEM) verification of a geometric calibration field. The approach focuses
on three modules: on-ground processing based on bidirectional filter, overall
weighted smoothing and fitting, and evaluation in the geometric calibration
field. Our experimental results demonstrate that the proposed on-ground
processing method is both robust and feasible, which ensures the reliability of
the observation data quality, convergence and stability of the parameter
estimation model. In addition, both the Euler angle and quaternion could be used
to build a mathematical fitting model, while the orthogonal polynomial fitting
model is more suitable for modeling the attitude parameter. Furthermore, compared
to the image geometric processing results based on on-board attitude data, the
image uncontrolled and relative geometric positioning result accuracy can be
increased by about 50%.
PMID- 27483288
TI - TRPV1 and TRPM8 in Treatment of Chronic Cough.
AB - Chronic cough is common in the population, and among some there is no evident
medical explanation for the symptoms. Such a refractory or idiopathic cough is
now often regarded as a neuropathic disease due to dysfunctional airway ion
channels, though the knowledge in this field is still limited. Persistent
coughing and a cough reflex easily triggered by irritating stimuli, often in
combination with perceived dyspnea, are characteristics of this disease. The
patients have impaired quality of life and often reduced work capacity, followed
by social and economic consequences. Despite the large number of individuals
suffering from such a persisting cough, there is an unmet clinical need for
effective cough medicines. The cough treatment available today often has little
or no effect. Adverse effects mostly follow centrally acting cough drugs
comprised of morphine and codeine, which demands the physician's awareness. The
possibilities of modulating airway transient receptor potential (TRP) ion
channels may indicate new ways to treat the persistent cough "without a reason".
The TRP ion channel vanilloid 1 (TRPV1) and the TRP melastin 8 (TRPM8) appear as
two candidates in the search for cough therapy, both as single targets and in
reciprocal interaction.
PMID- 27483289
TI - Differential Activation of TRP Channels in the Adult Rat Spinal Substantia
Gelatinosa by Stereoisomers of Plant-Derived Chemicals.
AB - Activation of TRPV1, TRPA1 or TRPM8 channel expressed in the central terminal of
dorsal root ganglion (DRG) neuron increases the spontaneous release of l
glutamate onto spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons
which play a pivotal role in regulating nociceptive transmission. The TRP
channels are activated by various plant-derived chemicals. Although stereoisomers
activate or modulate ion channels in a distinct manner, this phenomenon is not
fully addressed for TRP channels. By applying the whole-cell patch-clamp
technique to SG neurons of adult rat spinal cord slices, we found out that all of
plant-derived chemicals, carvacrol, thymol, carvone and cineole, increase the
frequency of spontaneous excitatory postsynaptic current, a measure of the
spontaneous release of l-glutamate from nerve terminals, by activating TRP
channels. The presynaptic activities were different between stereoisomers
(carvacrol and thymol; (-)-carvone and (+)-carvone; 1,8-cineole and 1,4-cineole)
in the extent or the types of TRP channels activated, indicating that TRP
channels in the SG are activated by stereoisomers in a distinct manner. This
result could serve to know the properties of the central terminal TRP channels
that are targets of drugs for alleviating pain.
PMID- 27483290
TI - 5-Episinuleptolide Decreases the Expression of the Extracellular Matrix in Early
Biofilm Formation of Multi-Drug Resistant Acinetobacter baumannii.
AB - Nosocomial infections and increasing multi-drug resistance caused by
Acinetobacter baumannii have been recognized as emerging problems worldwide.
Moreover, A. baumannii is able to colonize various abiotic materials and medical
devices, making it difficult to eradicate and leading to ventilator-associated
pneumonia, and bacteremia. Development of novel molecules that inhibit bacterial
biofilm formation may be an alternative prophylactic option for the treatment of
biofilm-associated A. baumannii infections. Marine environments, which are unlike
their terrestrial counterparts, harbor an abundant biodiversity of marine
organisms that produce novel bioactive natural products with pharmaceutical
potential. In this study, we identified 5-episinuleptolide, which was isolated
from Sinularia leptoclados, as an inhibitor of biofilm formation in ATCC 19606
and three multi-drug resistant A. baumannii strains. In addition, the anti
biofilm activities of 5-episinuleptolide were observed for Gram-negative bacteria
but not for Gram-positive bacteria, indicating that the inhibition mechanism of 5
episinuleptolide is effective against only Gram-negative bacteria. The mechanism
of biofilm inhibition was demonstrated to correlate to decreased gene expression
from the pgaABCD locus, which encodes the extracellular polysaccharide poly-beta
(1,6)-N-acetylglucosamine (PNAG). Scanning electron microscopy (SEM) indicated
that extracellular matrix of the biofilm was dramatically decreased by treatment
with 5-episinuleptolide. Our study showed potentially synergistic activity of
combination therapy with 5-episinuleptolide and levofloxacin against biofilm
formation and biofilm cells. These data indicate that inhibition of biofilm
formation via 5-episinuleptolide may represent another prophylactic option for
solving the persistent problem of biofilm-associated A. baumannii infections.
PMID- 27483291
TI - High-EPA Biomass from Nannochloropsis salina Cultivated in a Flat-Panel Photo
Bioreactor on a Process Water-Enriched Growth Medium.
AB - Nannochloropsis salina was grown on a mixture of standard growth media and pre
gasified industrial process water representing effluent from a local biogas
plant. The study aimed to investigate the effects of enriched growth media and
cultivation time on nutritional composition of Nannochloropsis salina biomass,
with a focus on eicosapentaenoic acid (EPA). Variations in fatty acid
composition, lipids, protein, amino acids, tocopherols and pigments were studied
and results compared to algae cultivated on F/2 media as reference. Mixed growth
media and process water enhanced the nutritional quality of Nannochloropsis
salina in laboratory scale when compared to algae cultivated in standard F/2
medium. Data from laboratory scale translated to the large scale using a 4000 L
flat panel photo-bioreactor system. The algae growth rate in winter conditions in
Denmark was slow, but results revealed that large-scale cultivation of
Nannochloropsis salina at these conditions could improve the nutritional
properties such as EPA, tocopherol, protein and carotenoids compared to
laboratory-scale cultivated microalgae. EPA reached 44.2% +/- 2.30% of total
fatty acids, and alpha-tocopherol reached 431 +/- 28 ug/g of biomass dry weight
after 21 days of cultivation. Variations in chemical compositions of
Nannochloropsis salina were studied during the course of cultivation.
Nannochloropsis salina can be presented as a good candidate for winter time
cultivation in Denmark. The resulting biomass is a rich source of EPA and also a
good source of protein (amino acids), tocopherols and carotenoids for potential
use in aquaculture feed industry.
PMID- 27483293
TI - Assessing the Contribution of the Environmental Parameters to Eutrophication with
the Use of the "PaD" and "PaD2" Methods in a Hypereutrophic Lake.
AB - Lake Pamvotis (Greece) is a shallow hypereutrophic lake with a natural tendency
to eutrophication. Several restoration measures were applied, but with no long
term success. To examine the causes for this an Artificial Neural Network (ANN)
was created in order to simulate the chlorophyll-a (Chl-a) levels and to
investigate the role of the associated environmental parameters. The ANN managed
to simulate with good correlation the simulated Chl-a and can be considered as a
reliable predictor. The relative importance of the environmental parameters to
the simulated Chl-a was calculated with the use of the "Partial Derivatives"
("PaD") sensitivity method. The water temperature (WT) and soluble reactive
phosphorus (SRP) had the highest relative importance, with values of 50% and 17%,
respectively. The synergistic effect of the paired parameters was calculated with
the use of the "PaD2" algorithm. The SRP-WT paired parameter was the most
influential, with a relative contribution of 22%. The ANN showed that Lake
Pamvotis is prone to suffer the effects of climatic change, because of the major
contribution of WT. The ANN also revealed that combined nutrients reduction would
improve water quality status. The ANN findings can act as an advisory tool
regarding any restoration efforts.
PMID- 27483294
TI - Bi-Objective Modelling for Hazardous Materials Road-Rail Multimodal Routing
Problem with Railway Schedule-Based Space-Time Constraints.
AB - The transportation of hazardous materials is always accompanied by considerable
risk that will impact public and environment security. As an efficient and
reliable transportation organization, a multimodal service should participate in
the transportation of hazardous materials. In this study, we focus on
transporting hazardous materials through the multimodal service network and
explore the hazardous materials multimodal routing problem from the operational
level of network planning. To formulate this problem more practicably, minimizing
the total generalized costs of transporting the hazardous materials and the
social risk along the planned routes are set as the optimization objectives.
Meanwhile, the following formulation characteristics will be comprehensively
modelled: (1) specific customer demands; (2) multiple hazardous material flows;
(3) capacitated schedule-based rail service and uncapacitated time-flexible road
service; and (4) environmental risk constraint. A bi-objective mixed integer
nonlinear programming model is first built to formulate the routing problem that
combines the formulation characteristics above. Then linear reformations are
developed to linearize and improve the initial model so that it can be
effectively solved by exact solution algorithms on standard mathematical
programming software. By utilizing the normalized weighted sum method, we can
generate the Pareto solutions to the bi-objective optimization problem for a
specific case. Finally, a large-scale empirical case study from the Beijing
Tianjin-Hebei Region in China is presented to demonstrate the feasibility of the
proposed methods in dealing with the practical problem. Various scenarios are
also discussed in the case study.
PMID- 27483292
TI - Fucoidans in Nanomedicine.
AB - Fucoidans are widespread cost-effective sulfated marine polysaccharides which
have raised interest in the scientific community over last decades for their wide
spectrum of bioactivities. Unsurprisingly, nanomedicine has grasped these
compounds to develop innovative therapeutic and diagnostic nanosystems. The
applications of fucoidans in nanomedicine as imaging agents, drug carriers or for
their intrinsic properties are reviewed here after a short presentation of the
main structural data and biological properties of fucoidans. The origin and the
physicochemical specifications of fucoidans are summarized in order to discuss
the strategy of fucoidan-containing nanosystems in Human health. Currently, there
is a need for reproducible, well characterized fucoidan fractions to ensure
significant progress.
PMID- 27483295
TI - Endocrine Aspects of Environmental "Obesogen" Pollutants.
AB - Growing evidence suggests the causal link between the endocrine-disrupting
chemicals (EDCs) and the global obesity epidemics, in the context in the so
called "obesogenic environment". Dietary intake of contaminated foods and water,
especially in association with unhealthy eating pattern, and inhalation of
airborne pollutants represent the major sources of human exposure to EDCs. This
is of particular concern in view of the potential impact of obesity on chronic
non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and
hormone-sensitive cancers. The key concept is the identification of adipose
tissue not only as a preferential site of storage of EDCs, but also as an
endocrine organ and, as such, susceptible to endocrine disruption. The timing of
exposure to EDCs is critical to the outcome of that exposure, with early lifetime
exposures (e.g., fetal or early postnatal) particularly detrimental because of
their permanent effects on obesity later in life. Despite that the mechanisms
operating in EDCs effects might vary enormously, this minireview is aimed to
provide a general overview on the possible association between the pandemics of
obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs
exposure and latent onset of obesity.
PMID- 27483296
TI - Expression of Hepcidin and Ferroportin in the Placenta, and Ferritin and
Transferrin Receptor 1 Levels in Maternal and Umbilical Cord Blood in Pregnant
Women with and without Gestational Diabetes.
AB - BACKGROUND: Regulation of iron transfer from mother to fetus via the placenta is
not fully understood and the relationship between stored iron status in the
mothers' serum and gestational diabetes (GDM) in case-control studies is
controversial. The present study aimed to detect circulating soluble transferrin
receptor (sTfR) and ferritin levels in maternal and umbilical cord blood. We also
examined the expression of hepcidin (Hep), transferrin receptor (TfR1), and
ferroportin (FPN) in the placenta in pregnant women with and without GDM at full
term. METHODS: Eighty-two women participated (42 with GDM and 40 without GDM
[controls]). Maternal samples were collected at 37-39 weeks' gestation. Umbilical
cord blood was collected at birth. Ferritin and sTfR levels in maternal serum and
umbilical cord blood, and Hep, TfR1, and FPN protein expression in plac enta were
compared between the GDM and non-GDM groups. Serum ferritin (SF) was measured by
electrochemiluminescence assay and sTfR was measured by ELISA. Hep, TfR1, and FPN
expression was measured by immunohistochemistry. RESULTS: Maternal serum sTfR
levels were significantly elevated in the GDM group compared with the non-GDM
group (p = 0.003). SF levels in cord blood in the GDM group were significantly
higher than those in the non-GDM group (p = 0.003). However, maternal hemoglobin
and SF, and umbilical cord sTfR levels were not different between the groups. In
placental tissue, FPN expression was higher and hepcidin expression was lower in
the GDM group compared with the non-GDM group (p = 0.000 and p = 0.044,
respectively). There was no significant difference in TfR1 between the groups (p
= 0.898). CONCLUSIONS: Women with GDM transport iron more actively than those
without GDM at term pregnancy. Maternal iron metabolism in GDM may play a role in
fetal/placental iron demand and in the overall outcome of pregnancy.
PMID- 27483298
TI - The Optimum Production Method for Quality Improvement of Recycled Aggregates
Using Sulfuric Acid and the Abrasion Method.
AB - There has been increased deconstruction and demolition of reinforced concrete
structures due to the aging of the structures and redevelopment of urban areas
resulting in the generation of massive amounts of construction. The production
volume of waste concrete is projected to increase rapidly over 100 million tons
by 2020. However, due to the high cement paste content, recycled aggregates have
low density and high absorption ratio. They are mostly used for land reclamation
purposes with low added value instead of multiple approaches. This study was
performed to determine an effective method to remove cement paste from recycled
aggregates by using the abrasion and substituting the process water with acidic
water. The aim of this study is to analyze the quality of the recycled fine
aggregates produced by a complex method and investigate the optimum manufacturing
conditions for recycled fine aggregates based on the design of experiment. The
experimental parameters considered were water ratio, coarse aggregate ratio, and
abrasion time and, as a result of the experiment, data concerning the properties
of recycled sand were obtained. It was found that high-quality recycled fine
aggregates can be obtained with 8.57 min of abrasion-crusher time and a recycled
coarse aggregate ratio of over 1.5.
PMID- 27483297
TI - Polybrominated Diphenyl Ethers in Maternal Serum, Breast Milk, Umbilical Cord
Serum, and House Dust in a South Korean Birth Panel of Mother-Neonate Pairs.
AB - Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants.
Although many reports have indicated an association between exposure to PBDEs and
developmental neurotoxicity, the relative contributions of different sources of
dust PBDE congeners to the levels in various tissues of mother-baby pairs is not
well understood. The aims of this study were thus to measure the quantitative
relationship between the level of PBDEs in house dust and tissues of mother
neonate pairs, and to investigate the chemical sources of the PBDEs. Forty-one
mother-neonate pairs were recruited and provided samples of maternal serum (n =
29), umbilical cord serum (n = 25), breast milk (n = 50), and house dust (n =
41), where PBDEs were determined with high-resolution gas chromatography coupled
with high-resolution mass spectrometry. While deca- (e.g., BDE 209, detected
100%), nona- (BDE 206/207, 95.1%), octa- (BDE 183, 100%), penta- (BDE 99/153,
100%, 98%) and tetra-BDEs (BDE 47, 100%) were detected abundantly in dust, penta-
(BDE 99, 76%, 92%) and tetra-BDEs (BDE 47, 84%, 98%) were detected abundantly in
umbilical cord serum and breast milk, respectively; tetra-BDEs (BDE 47, 86%) were
detected more often relative to other congeners in maternal serum. Spearman's
pairwise comparison showed that the levels of BDE 47 (rho = 0.52, p < 0.001) and
99 (rho = 0.64, p < 0.01) in umbilical cord serum were associated with BDE 209
levels in dust; BDE 47 in maternal serum also showed correlation with BDE 99 in
cord serum (rho = 0.48, p < 0.01) but there was no significant correlation
between maternal BDE 47 and dust BDE 209. On the other hand, a comparison of the
distribution among congeners suggested probable associations of BDE 47 in
maternal serum, breast milk, and umbilical cord serum with BDE 209 in dust; and
of BDE 99 in maternal and umbilical cord serum, breast milk, and dust with BDE
209 in dust. Although further studies are needed, a radar chart-based
distributional comparison among congeners supported associations between BDE 47
or -99 in human tissues and BDE 209 in dust.
PMID- 27483299
TI - Analysis of Consumption of Energy Drinks by a Group of Adolescent Athletes.
AB - BACKGROUND: Energy drinks (EDs) have become widely popular among young adults
and, even more so, among adolescents. Increasingly, they are consumed by
athletes, particularly those who have just begun their sporting career.
Uncontrolled and high consumption of EDs, in addition to other sources of
caffeine, may pose a threat to the health of young people. Hence, our objective
was to analyze the consumption of EDs among teenagers engaged in sports,
including quantity consumed, identification of factors influencing consumption,
and risks associated with EDs and EDs mixed with alcohol (AmEDs). METHODS: The
study involved a specially designed questionnaire, which was completed by 707
students, 14.3 years of age on average, attending secondary sports schools.
RESULTS: EDs were consumed by 69% of the young athletes, 17% of whom drank EDs
quite often: every day or 1-3 times a week. Most respondents felt no effects
after drinking EDs, but some reported symptoms, including insomnia, anxiety,
tachycardia, nervousness and irritability. The major determinant of the choice of
EDs was taste (47%), followed by price (21%). One in ten respondents admitted to
consumption of AmEDs. Among the consequences reported were: abdominal pains,
nausea, vomiting, amnesia, headache, and hangover. CONCLUSIONS: EDs consumption
among adolescent athletes was relatively high. Considering the habit of AmEDs and
literature data, it is worth emphasizing that it may lead to health problems in
the near future, alcohol- or drug-dependence, as well as other types of risk
behaviour.
PMID- 27483300
TI - Prevalence and Risk Factors of Heart Failure with Preserved Ejection Fraction: A
Population-Based Study in Northeast China.
AB - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has attracted
increasing attention worldwide. We aimed to estimate the prevalence of HFpEF and
analyze its correlates in a sample of residents of northeast China; METHODS: A
population-based study of 2230 participants >=35 years old was conducted in rural
areas of Liaoning Province from January 2012 through August 2013. Information
about lifestyle and other potential risk factors was obtained. HFpEF was
diagnosed according to the recommendations of European Society of Cardiology;
RESULTS: The overall prevalence of HFpEF was 3.5% (1.8% in men and 4.9% in
women). The prevalence of HFpEF increased with age in both genders and was
greater in women than in men for every age group. Multivariable logistic
regression analysis found that female gender (OR, 3.575; 95% CI, 1.761-7.256),
hypertension (OR, 3.711; 95% CI, 2.064-6.674), and history of heart disease
(2.086; 95% CI, 1.243-3.498) were associated factors for prevalent HFpEF;
CONCLUSIONS: In a general population from rural northeast China, we found that
female gender, hypertension, and history of heart disease were risk factors for
prevalent HFpEF.
PMID- 27483301
TI - Measles Virus Host Invasion and Pathogenesis.
AB - Measles virus is a highly contagious negative strand RNA virus that is
transmitted via the respiratory route and causes systemic disease in previously
unexposed humans and non-human primates. Measles is characterised by fever and
skin rash and usually associated with cough, coryza and conjunctivitis. A
hallmark of measles is the transient immune suppression, leading to increased
susceptibility to opportunistic infections. At the same time, the disease is
paradoxically associated with induction of a robust virus-specific immune
response, resulting in lifelong immunity to measles. Identification of CD150 and
nectin-4 as cellular receptors for measles virus has led to new perspectives on
tropism and pathogenesis. In vivo studies in non-human primates have shown that
the virus initially infects CD150+ lymphocytes and dendritic cells, both in
circulation and in lymphoid tissues, followed by virus transmission to nectin-4
expressing epithelial cells. The abilities of the virus to cause systemic
infection, to transmit to numerous new hosts via droplets or aerosols and to
suppress the host immune response for several months or even years after
infection make measles a remarkable disease. This review briefly highlights
current topics in studies of measles virus host invasion and pathogenesis.
PMID- 27483302
TI - NXT1, a Novel Influenza A NP Binding Protein, Promotes the Nuclear Export of NP
via a CRM1-Dependent Pathway.
AB - Influenza remains a serious worldwide public health problem. After infection,
viral genomic RNA is replicated in the nucleus and packed into viral
ribonucleoprotein, which will then be exported to the cytoplasm via a cellular
chromosome region maintenance 1 (CRM1)-dependent pathway for further assembly and
budding. However, the nuclear export mechanism of influenza virus remains
controversial. Here, we identify cellular nuclear transport factor 2 (NTF2)-like
export protein 1 (NXT1) as a novel binding partner of nucleoprotein (NP) that
stimulates NP-mediated nuclear export via the CRM1-dependent pathway. NXT1
knockdown cells exhibit decreased viral replication kinetics and nuclear
accumulated viral RNA and NP. By contrast, NXT1 overexpression promotes nuclear
export of NP in a CRM1-dependent manner. Pull-down assays suggest the formation
of an NXT1, NP, and CRM1 complex, and demonstrate that NXT1 binds to the C
terminal region of NP. These findings reveal a distinct mechanism for nuclear
export of the influenza virus and identify the NXT1/NP interaction as a potential
target for antiviral drug development.
PMID- 27483303
TI - Low Iron Diet Increases Susceptibility to Noise-Induced Hearing Loss in Young
Rats.
AB - We evaluated the role of iron deficiency (ID) without anemia on hearing function
and cochlear pathophysiology of young rats before and after noise exposure. We
used rats at developmental stages as an animal model to induce ID without anemia
by dietary iron restriction. We have established this dietary restriction model
in the rat that should enable us to study the effects of iron deficiency in the
absence of severe anemia on hearing and ribbon synapses. Hearing function was
measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem
response (ABR). Then, the young rats were exposed to loud noise on PND 21. After
noise exposure, hearing function was again measured. We observed the morphology
of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the
expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the
cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR
wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave
I (3.11 +/- 0.96 uV, 3.52 +/- 1.31 uV, and 4.37 +/- 1.08 uV, respectively) in
pups from the ID group were decreased compared to the control (5.92 +/- 1.67 uV,
6.53 +/- 1.70 uV, and 6.90 +/- 1.76 uV, respectively) (p < 0.05). Moreover, ID
without anemia did not impair the morphology hair cells and SGCs, but decreased
the number of ribbon synapses. Before noise exposure, the mean number of ribbon
synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44
+/- 1.21) compared to that seen in the control (13.08 +/- 1.36) (p < 0.05). In
addition, the numbers of ribbon synapses per IHC of young rats in the control (ID
group) were 6.61 +/- 1.59, 3.07 +/- 0.83, 5.85 +/- 1.63 and 12.25 +/- 1.97 (3.75
+/- 1.45, 2.03 +/- 1.08, 3.81 +/- 1.70 and 4.01 +/- 1.65) at 1, 4, 7 and 14 days
after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in
young rats from the ID group were significantly elevated at 7 and 14 days after
noise exposure compared to control (p < 0.05). The average number of young rat
SGCs from the ID group were significantly decreased in the basal turn of the
cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed
the recovery from noise-induced hearing loss and ribbon synapses damage,
increased SGCs loss, and upregulated prestin after noise exposure. Thus, the
cochleae in rat pups with ID without anemia were potentially susceptible to loud
noise exposure, and this deficit may be attributed to the reduction of ribbon
synapses and SGCs.
PMID- 27483304
TI - Validity and Reproducibility of a Dietary Questionnaire for Consumption
Frequencies of Foods during Pregnancy in the Born in Guangzhou Cohort Study
(BIGCS).
AB - This study aimed to examine the reproducibility and validity of a new food
frequency questionnaire (FFQ) used in a birth cohort study to estimate the usual
consumption frequencies of foods during pregnancy. The reference measure was the
average of three inconsecutive 24 h diet recalls (24 HR) administrated between
two FFQs, and the reproducibility was measured by repeating the first FFQ (FFQ1)
approximately eight weeks later (FFQ2). A total of 210 pregnant women from the
Born in Guangzhou Cohort Study (BIGCS) with full data were included in the
analysis. The Spearman's correlation coefficients of FFQ1 and FFQ2 ranged from
0.33 to 0.71. The intraclass correlation coefficients of the two FFQs ranged from
0.22 to 0.71. The Spearman's correlation coefficients of the 24 HR and FFQ2
ranged from 0.23 to 0.62. Cross-classification analysis showed 65.1% of
participants were classified into same and contiguous quintiles, while only 3.2%
were misclassified into the distant quintiles. Bland-Altman methods showed good
agreement for most food groups across the range of frequencies between FFQ1 and
FFQ2. Our findings indicated that the reproducibility and validity of the FFQ
used in BIGCS for assessing the usual consumption frequencies of foods during
pregnancy were acceptable.
PMID- 27483305
TI - Suppressive Effects of Tea Catechins on Breast Cancer.
AB - Tea leaf (Camellia sinensis) is rich in catechins, which endow tea with various
health benefits. There are more than ten catechin compounds in tea, among which
epigallocatechingallate (EGCG) is the most abundant. Epidemiological studies on
the association between tea consumption and the risk of breast cancer were
summarized, and the inhibitory effects of tea catechins on breast cancer, with
EGCG as a representative compound, were reviewed in the present paper. The
controversial results regarding the role of tea in breast cancer and areas for
further study were discussed.
PMID- 27483306
TI - The Association of Vitamin D Status with Dyslipidaemia and Biomarkers of
Endothelial Cell Activation in Older Australians.
AB - BACKGROUND/AIMS: Vitamin D has been investigated for many non-skeletal effects.
The objective of this study was to determine whether circulating lipids, systemic
inflammation, and biomarkers of endothelial cell activation varied with the
vitamin D status of older Australians. METHODS: One hundred and one participants
were proportionately and randomly sampled across tertiles of 25 hydroxy vitamin D
(25(OH)D) from a larger cohort of free living older adults (T1 median = 97; T2
median = 74.5; T3 median = 56.8 nmol/L). Overnight fasting blood samples were
assayed for 25(OH)D, parathyroid hormone (PTH), insulin, triacylglycerol (TAG),
total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high
density lipoprotein cholesterol (HDL-C). Markers of systemic inflammation (high
sensitivity C-reactive protein (hsCRP), tumour necrosis factor-alpha (TNF-alpha))
and endothelial activation (hepatocyte growth factor (HGF), P-selectin and
soluble vascular cell adhesion molecule (sVCAM), soluble intracellular adhesion
molecule (sICAM)) were determined. A general linear model multivariate analysis
with a backward elimination procedure was performed. RESULTS: Eighty-three
participants (48 women, 35 men), aged 65 +/- 7.7 years, BMI 28 +/- 4.5 kg/m2,
with complete data were analyzed. The final parsimonious model controlled for
age, gender, BMI, and McAuley's index, but excluded season, medications, and PTH.
There were significant differences across 25(OH)D tertiles in TC (T1 < T3, p =
0.003; T2 < T3, p = 0.001), LDL-C (T1 < T3, p = 0.005; T2 < T3, p = 0.001), TAG
(T2 < T3, p = 0.026), HGF (T1 > T3, p = 0.009) and sVCAM (T1 > T3, P = 0.04).
CONCLUSIONS: Higher vitamin D status may protect the endothelium through reduced
dyslipidaemia and increased HGF.
PMID- 27483307
TI - Dietary Interventions and Changes in Cardio-Metabolic Parameters in Metabolically
Healthy Obese Subjects: A Systematic Review with Meta-Analysis.
AB - The aim of this systematic review was to assess the effect of diet on changes in
parameters describing the body size phenotype of metabolically healthy obese
subjects. The databases Medline, Scopus, Web of Knowledge and Embase were
searched for clinical studies carried out between 1958 and June 2016 that
reported the effect of dietary intervention on BMI, blood pressure, concentration
of fasting triglyceride (TG), high density lipoprotein cholesterol (HDL-C),
fasting glucose level, the homoeostatic model assessment of insulin resistance
(HOMA-IR) and high sensitivity C-Reactive Protein (hsCRP) in metabolically
healthy, obese subjects. Twelve clinical studies met inclusion criteria. The
combined analyzed population consists of 1827 subjects aged 34.4 to 61.1 with a
BMI > 30 kg/m2. Time of intervention ranged from eight to 104 weeks. The baseline
characteristics related to lipid profile were more favorable for metabolically
healthy obese than for metabolically unhealthy obese. The meta-analyses revealed
a significant associations between restricted energy diet and BMI (95% confidence
interval (CI): -0.88, -0.19), blood pressure (systolic blood pressure (SBP):
4.73 mmHg; 95% CI: -7.12, -2.33; and diastolic blood pressure (DBP): -2.75 mmHg;
95% CI: -4.30, -1.21) and TG (-0.11 mmol/l; 95% CI: -0.16, -0.06). Changes in
fasting glucose, HOMA-IR and hsCRP did not show significant changes. Sufficient
evidence was not found to support the use of specific diets in metabolically
healthy obese subjects. This analysis suggests that the effect of caloric
restriction exerts its effects through a reduction in BMI, blood pressure and
triglycerides in metabolically healthy obese (MHO) patients.
PMID- 27483309
TI - Trends and Predictors of Prelacteal Feeding Practices in Nigeria (2003-2013).
AB - Prelacteal feeding practices are associated with an increased risk of diarrhoea
and many early-life diseases. This paper examined trends and predictors of
prelacteal feeding practices in Nigeria. A sample of 6416 infants aged 0-6 months
from the Nigeria Demographic and Health Survey data for the period (2003-2013)
was used. Trends and multilevel logistic regression analyses were used to
determine the predictors. The trends of prelacteal feeding rates fluctuated
between 55% and 66% over the study period and were significantly lower among
mothers with secondary or higher levels of education (13.1%, 95% confidence
interval (CI): 0.54-25.9, p-value = 0.041), delivered at the health facility
(13.7%, CI: 1.39-25.9, p-value = 0.029), from more affluent households (18.7%,
CI: 1.53-35.9, p-value = 0.033), and lived in urban areas (26.9%, CI: 18.3-35.5,
p-value < 0.001). Multivariable analyses revealed that mothers with no schooling,
younger mothers (aged 15-24 years), mothers who delivered at home, and delivered
by caesarean section were more likely to introduce prelacteal feeds. Many mothers
still engage in prelacteal feeding practices in Nigeria, with prelacteal feeding
more prevalent in young mothers, mothers with no schooling, and mothers who
delivered at home. Interventions involving community health volunteers are needed
to improve feeding practices in Nigeria.
PMID- 27483308
TI - Regular-Fat Dairy and Human Health: A Synopsis of Symposia Presented in Europe
and North America (2014-2015).
AB - In recent history, some dietary recommendations have treated dairy fat as an
unnecessary source of calories and saturated fat in the human diet. These
assumptions, however, have recently been brought into question by current
research on regular fat dairy products and human health. In an effort to
disseminate, explore and discuss the state of the science on the relationship
between regular fat dairy products and health, symposia were programmed by dairy
industry organizations in Europe and North America at The Eurofed Lipids Congress
(2014) in France, The Dairy Nutrition Annual Symposium (2014) in Canada, The
American Society for Nutrition Annual Meeting held in conjunction with
Experimental Biology (2015) in the United States, and The Federation of European
Nutrition Societies (2015) in Germany. This synopsis of these symposia describes
the complexity of dairy fat and the effects regular-fat dairy foods have on human
health. The emerging scientific evidence indicates that the consumption of
regular fat dairy foods is not associated with an increased risk of
cardiovascular disease and inversely associated with weight gain and the risk of
obesity. Dairy foods, including regular-fat milk, cheese and yogurt, can be
important components of an overall healthy dietary pattern. Systematic
examination of the effects of dietary patterns that include regular-fat milk,
cheese and yogurt on human health is warranted.
PMID- 27483310
TI - Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human
Keratinocytes.
AB - Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the
cells, which induces the cellular senescence and photoaging. The present study
investigated the protective effects of garlic on photo-damage and cellular
senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free
system was used to examine the scavenging activity of 2,2-diphenyl-1
picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic
extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as
interleukin (IL)-1beta and IL-6, senescence associated-beta-galactosidase (SA
beta-gal) activity, and silent information regulator T1 (SIRT1) activity were
determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical
and NO scavenging activity in cell free system exhibiting IC50 values of 2.50
mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production
of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced
by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA
and protein expressions were significantly reduced by garlic treatment (50 ug/mL)
comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory
cytokine productions (IL-6 and IL-1beta) were significantly inhibited by
pretreatment with garlic in a dose-dependent manner. SA-beta-gal activity, a
classical biomarker of cellular senescence, and SIRT1 activity, which has
attracted attention as an anti-aging factor in recent years, were ameliorated by
garlic treatment in UV-irradiated HaCaT cells. The present study provides the
first evidence of garlic inhibiting UVB-induced photoaging as a result of
augmentation of cellular senescence in HaCaT human keratinocytes.
PMID- 27483311
TI - Lipid-Induced Insulin Resistance in Skeletal Muscle: The Chase for the Culprit
Goes from Total Intramuscular Fat to Lipid Intermediates, and Finally to Species
of Lipid Intermediates.
AB - The skeletal muscle is the largest organ in the body. It plays a particularly
pivotal role in glucose homeostasis, as it can account for up to 40% of the body
and for up to 80%-90% of insulin-stimulated glucose disposal. Hence, insulin
resistance (IR) in skeletal muscle has been a focus of much research and review.
The fact that skeletal muscle IR precedes beta-cell dysfunction makes it an ideal
target for countering the diabetes epidemic. It is generally accepted that the
accumulation of lipids in the skeletal muscle, due to dietary lipid oversupply,
is closely linked with IR. Our understanding of this link between
intramyocellular lipids (IMCL) and glycemic control has changed over the years.
Initially, skeletal muscle IR was related to total IMCL. The inconsistencies in
this explanation led to the discovery that particular lipid intermediates are
more important than total IMCL. The two most commonly cited lipid intermediates
for causing skeletal muscle IR are ceramides and diacylglycerol (DAG) in IMCL.
Still, not all cases of IR and dysfunction in glycemic control have shown an
increase in either or both of these lipids. In this review, we will summarise the
latest research results that, using the lipidomics approach, have elucidated DAG
and ceramide species that are involved in skeletal muscle IR in animal models and
human subjects.
PMID- 27483312
TI - A Diet Score Assessing Norwegian Adolescents' Adherence to Dietary
Recommendations-Development and Test-Retest Reproducibility of the Score.
AB - Assessment of adolescents' dietary habits is challenging. Reliable instruments to
monitor dietary trends are required to promote healthier behaviours in this
group. The purpose of this cross-sectional study was to assess adolescents'
adherence to Norwegian dietary recommendations with a diet score and to report
results from, and test-retest reliability of, the score. The diet score involved
seven food groups and one physical activity indicator, and was applied to answers
from a semi-quantitative food frequency questionnaire (FFQ) administered twice.
Reproducibility of the score was assessed with Cohen's Kappa (kappa statistics)
at an interval of three months. The setting was eight lower-secondary schools in
Hordaland County, Norway, and subjects were adolescents (n = 472) aged 14-15
years and their caregivers. Results showed that the proportion of adolescents
consistently classified by the diet score was 87.6% (kappa = 0.465). For food
groups, proportions ranged from 74.0% to 91.6% (kappa = 0.249 to kappa = 0.573).
Less than 40% of the participants were found to adhere to recommendations for
frequencies of eating fruits, vegetables, added sugar, and fish. Highest
compliance to recommendations was seen for choosing water as beverage and limit
the intake of red meat. The score was associated with parental socioeconomic
status. The diet score was found to be reproducible at an acceptable level.
Health promoting work targeting adolescents should emphasize to increase the
intake of recommended foods to approach nutritional guidelines.
PMID- 27483313
TI - Usual Intake of Key Minerals among Children in the Second Year of Life, NHANES
2003-2012.
AB - Iron, calcium, and zinc are important nutrients for the young, developing child.
This study describes the usual intake of iron, calcium, and zinc among US
children in the second year of life using two days of dietary intake data from
the National Health and Nutrition Examination Survey 2003-2012. Estimates were
calculated using PC-SIDE to account for within and between person variation. Mean
usual iron, calcium, and zinc intakes were 9.5 mg/day, 1046 mg/day, and 7.1
mg/day, respectively. Over a quarter of children had usual iron intakes less than
the Recommended Dietary Allowance (RDA) (26.1%). Eleven percent of children had
usual calcium intakes below the RDA and over half of children had usual intakes
of zinc that exceeded the tolerable upper intake level (UL). Two percent or less
had usual intakes below the Estimated Average Requirement (EAR) for iron,
calcium, and zinc. Our findings suggest that during 2003-2012, one in four
children and one in ten children had usual intakes below the RDA for iron and
calcium, respectively. Children who are not meeting their nutrient requirements
could be at increased risk for developing deficiencies such as iron deficiency or
could lead to a shortage in adequate nutrients required for growth and
development. One in every two children is exceeding the UL for zinc, but the
interpretation of these estimates should be done with caution given the limited
data on adverse health outcomes. Continued monitoring of zinc intake and further
assessment for the potential of adverse health outcomes associated with high zinc
intakes may be needed.
PMID- 27483314
TI - Lean Mass and Body Fat Percentage Are Contradictory Predictors of Bone Mineral
Density in Pre-Menopausal Pacific Island Women.
AB - Anecdotally, it is suggested that Pacific Island women have good bone mineral
density (BMD) compared to other ethnicities; however, little evidence for this or
for associated factors exists. This study aimed to explore associations between
predictors of bone mineral density (BMD, g/cm2), in pre-menopausal Pacific Island
women. Healthy pre-menopausal Pacific Island women (age 16-45 years) were
recruited as part of the larger EXPLORE Study. Total body BMD and body
composition were assessed using Dual X-ray Absorptiometry and air-displacement
plethysmography (n = 83). A food frequency questionnaire (n = 56) and current
bone-specific physical activity questionnaire (n = 59) were completed. Variables
expected to be associated with BMD were applied to a hierarchical multiple
regression analysis. Due to missing data, physical activity and dietary intake
factors were considered only in simple correlations. Mean BMD was 1.1 +/- 0.08
g/cm2. Bone-free, fat-free lean mass (LMO, 52.4 +/- 6.9 kg) and age were
positively associated with BMD, and percent body fat (38.4 +/- 7.6) was inversely
associated with BMD, explaining 37.7% of total variance. Lean mass was the
strongest predictor of BMD, while many established contributors to bone health
(calcium, physical activity, protein, and vitamin C) were not associated with BMD
in this population, partly due to difficulty retrieving dietary data. This
highlights the importance of physical activity and protein intake during any
weight loss interventions to in order to minimise the loss of muscle mass, whilst
maximizing loss of adipose tissue.
PMID- 27483316
TI - Dietary Inflammatory Index and Risk of Colorectal Cancer: A Case-Control Study in
Korea.
AB - The role of diet-associated inflammation in colorectal cancer is of interest.
Accordingly, we aimed to examine whether the dietary inflammatory index (DII) was
associated with the risk of colorectal cancer in a case-control study conducted
in Korea. The DII was based on dietary intake, which was determined by a 106-item
semi-quantitative food frequency questionnaire completed by 923 colorectal cancer
cases and 1846 controls. Logistic regression was used to estimate odd ratios
(ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by the
anatomical site of the cancer, sex, and other risk factors. Higher DII scores
were associated with an increased incidence of colorectal cancer (OR (95% CI) =
2.16 (1.71, 2.73) for highest vs. lowest tertile). The magnitude differed by
anatomical site and sex. This association was slightly weaker in subjects with
proximal colon cancer (1.68 (1.08, 2.61)) and was stronger in women (2.50 (1.64,
3.82)). Additionally, stronger associations were observed in subjects who were
older than 50 years (p for interaction = 0.004) and engaged in physical activity
(p for interaction < 0.001). Results from this study suggest that diet-associated
inflammation may increase the risk of colorectal cancer, and this effect may
differ by certain factors, such as anatomical site, age, sex, and lifestyle.
PMID- 27483315
TI - Bioactive Compounds and Their Neuroprotective Effects in Diabetic Complications.
AB - Hyperglycemia, hyperlipidemia and impaired insulin signaling during the
development of diabetes can cause diabetic complications, such as diabetic
neuropathy, resulting in significant morbidity and mortality. Although various
therapeutics are available for the treatment of diabetic neuropathy, no absolute
cure exists, and additional research is necessary to comprehensively understand
the underlying pathophysiological pathways. A number of studies have demonstrated
the potential health benefits of bioactive compounds, i.e., flavonoids and
vitamins, which may be effective as supplementary treatments for diabetes and its
complications. In this review, we highlight the most recent reports about the
mechanisms of action of bioactive compounds (flavonoids and vitamins) possessing
potential neuroprotective properties in diabetic conditions. Additional clinical
studies are required to determine the appropriate dose and duration of bioactive
compound supplementation for neuroprotection in diabetic patients.
PMID- 27483317
TI - Protein-Pacing Caloric-Restriction Enhances Body Composition Similarly in Obese
Men and Women during Weight Loss and Sustains Efficacy during Long-Term Weight
Maintenance.
AB - Short-Term protein-pacing (P; ~6 meals/day, >30% protein/day) and caloric
restriction (CR, ~25% energy deficit) improves total (TBF), abdominal (ABF) and
visceral (VAT) fat loss, energy expenditure, and biomarkers compared to heart
healthy (HH) recommendations (3 meals/day, 15% protein/day) in obese adults. Less
is known whether obese men and women respond similarly to P-CR during weight loss
(WL) and whether a modified P-CR (mP-CR) is more efficacious than a HH diet
during long-term (52 week) weight maintenance (WM). The purposes of this study
were to evaluate the efficacy of: (1) P-CR on TBF, ABF, resting metabolic rate
(RMR), and biomarkers between obese men and women during WL (weeks 0-12); and (2)
mP-CR compared to a HH diet during WM (weeks 13-64). During WL, men (n = 21) and
women (n = 19) were assessed for TBF, ABF, VAT, RMR, and biomarkers at weeks 0
(pre) and 12 (post). Men and women had similar reductions (p < 0.01) in weight
(10%), TBF (19%), ABF (25%), VAT (33%), glucose (7%-12%), insulin (40%), leptin
(>50%) and increase in % lean body mass (9%). RMR (kcals/kg bodyweight) was
unchanged and respiratory quotient decreased 9%. Twenty-four subjects (mP-CR, n =
10; HH, n = 14) completed WM. mP-CR regained significantly less body weight (6%),
TBF (12%), and ABF (17%) compared to HH (p < 0.05). Our results demonstrate P-CR
enhances weight loss, body composition and biomarkers, and maintains these
changes for 52-weeks compared to a traditional HH diet.
PMID- 27483318
TI - Beverage Intake Assessment Questionnaire: Relative Validity and Repeatability in
a Spanish Population with Metabolic Syndrome from the PREDIMED-PLUS Study.
AB - We assess the repeatability and relative validity of a Spanish beverage intake
questionnaire for assessing water intake from beverages. The present analysis was
performed within the framework of the PREDIMED-PLUS trial. The study participants
were adults (aged 55-75) with a BMI >=27 and <40 kg/m2, and at least three
components of Metabolic Syndrome (MetS). A trained dietitian completed the
questionnaire. Participants provided 24-h urine samples, and the volume and urine
osmolality were recorded. The repeatability of the baseline measurement at 6 and
1 year was examined by paired Student's t-test comparisons. A total of 160
participants were included in the analysis. The Bland-Altman analysis showed
relatively good agreement between total daily fluid intake assessed using the
fluid-specific questionnaire, and urine osmolality and 24-h volume with parameter
estimates of -0.65 and 0.22, respectively (R2 = 0.20; p < 0.001). In the
repeatability test, no significant differences were found between neither type of
beverage nor total daily fluid intake at 6 months and 1-year assessment, compared
to baseline. The proposed fluid-specific assessment questionnaire designed to
assess the consumption of water and other beverages in Spanish adult individuals
was found to be relatively valid with good repeatability.
PMID- 27483320
TI - Associations of Fat Mass and Fat-Free Mass with Physical Fitness in 4-Year-Old
Children: Results from the MINISTOP Trial.
AB - Physical fitness is a powerful marker of health in youth. Studies in adolescents
and adults suggest that higher fat mass is related to worse physical fitness.
However, there is limited knowledge whether fat mass and fat-free mass are
associated with physical fitness already in preschoolers. Baseline data from the
MINISTOP (Mobile-based INtervention Intended to STop Obesity in Preschoolers)
trial was utilized for this cross-sectional analysis. Body composition was
assessed using air-displacement plethysmography. Fat mass index [fat mass
(kg)/height2 (m)] and fat-free mass index [fat-free mass (kg)/height2 (m)] were
used to provide height-adjusted measures of body composition. Physical fitness
was measured using the PREFIT (FITness testing in PREschool children) battery,
which assesses cardiorespiratory fitness, upper-body and lower-body muscular
strength as well as motor fitness. In total, this study included 303 children
(168 boys and 135 girls), who were on average 4.48 +/- 0.15 years old. Higher fat
mass index was associated with worse cardiorespiratory fitness (standardized beta
= -0.17, p = 0.002), lower-body muscular strength (beta = -0.17, p = 0.003) and
motor fitness (beta = -0.21, p < 0.001) in regression analyses adjusted for age,
sex and mutually adjusted for fat-mass index and fat-free mass index. Conversely,
higher fat-free mass index was associated with better cardiorespiratory fitness
(beta = 0.18, p = 0.002), upper-body muscular strength (beta = 0.39, p < 0.001),
lower-body muscular strength (beta = 0.22, p < 0.001) and motor fitness (beta =
0.17, p = 0.004). Thus, fat mass and fat-free mass in preschoolers appear to have
joint but opposite associations with physical fitness, an important marker for
current and future health.
PMID- 27483319
TI - Probiotics and Time to Achieve Full Enteral Feeding in Human Milk-Fed and Formula
Fed Preterm Infants: Systematic Review and Meta-Analysis.
AB - Probiotics have been linked to a reduction in the incidence of necrotizing
enterocolitis and late-onset sepsis in preterm infants. Recently, probiotics have
also proved to reduce time to achieve full enteral feeding (FEF). However, the
relationship between FEF achievement and type of feeding in infants treated with
probiotics has not been explored yet. The aim of this systematic review and meta
analysis was to evaluate the effect of probiotics in reducing time to achieve FEF
in preterm infants, according to type of feeding (exclusive human milk (HM) vs.
formula). Randomized-controlled trials involving preterm infants receiving
probiotics, and reporting on time to reach FEF were included in the systematic
review. Trials reporting on outcome according to type of feeding (exclusive HM
vs. formula) were included in the meta-analysis. Fixed-effect or random-effects
models were used as appropriate. Results were expressed as mean difference (MD)
with 95% confidence interval (CI). Twenty-five studies were included in the
systematic review. In the five studies recruiting exclusively HM-fed preterm
infants, those treated with probiotics reached FEF approximately 3 days before
controls (MD -3.15 days (95% CI -5.25/-1.05), p = 0.003). None of the two studies
reporting on exclusively formula-fed infants showed any difference between
infants receiving probiotics and controls in terms of FEF achievement. The
limited number of included studies did not allow testing for other subgroup
differences between HM and formula-fed infants. However, if confirmed in further
studies, the 3-days reduction in time to achieve FEF in exclusively HM-fed
preterm infants might have significant implications for their clinical
management.
PMID- 27483321
TI - Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by
the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches.
AB - In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and
15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure
to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted
into DON after their ingestion through hydrolysis of the acetyl moiety, the
site(s) of such deacetylation being still uncharacterized. We used in vitro and
ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and
cells/tissues present on their way from the food matrix to the blood in humans.
We found that luminal deacetylation by digestive enzymes and bacteria is limited.
Using human cells, tissues and S9 fractions, we were able to demonstrate that
small intestine and liver possess strong deacetylation capacity compared to colon
and kidneys. Interestingly, in most cases, deacetylation was more efficient for
3ADON than 15ADON. Although we initially thought that carboxylesterases (CES)
could be responsible for the deacetylation of 3/15ADON, the use of pure human
CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken
together, our original model system allowed us to identify the small intestine
and the liver as the main site of deacetylation of ingested 3/15ADON in humans.
PMID- 27483322
TI - Human Papillomavirus Genotype Distribution in Invasive Cervical Cancer in
Pakistan.
AB - Few studies have assessed the burden of human papillomavirus (HPV) infection in
Pakistan. We aim to provide specific information on HPV-type distribution in
invasive cervical cancer (ICC) in the country. A total of 280 formalin-fixed
paraffin-embedded tissue blocks were consecutively selected from Shaukat Khanum
Memorial Cancer Hospital and Research Centre (Lahore, Pakistan). HPV-DNA was
detected by SPF10 broad-spectrum PCR followed by DNA enzyme immunoassay and
genotyping by LiPA25. HPV-DNA prevalence was 87.5% (95%CI: 83.0-91.1), with 96.1%
of cases histologically classified as squamous cell carcinoma. Most of the HPV
DNA positive cases presented single infections (95.9%). HPV16 was the most common
type followed by HPV18 and 45. Among HPV-DNA positive, a significantly higher
contribution of HPV16/18 was detected in Pakistan (78.4%; 72.7-83.3), compared to
Asia (71.6%; 69.9-73.4) and worldwide (70.8%; 69.9-71.8) and a lower contribution
of HPVs31/33/45/52/58 (11.1%; 7.9-15.7 vs. 19.8%; 18.3-21.3 and 18.5%; 17.7
19.3). HPV18 or HPV45 positive ICC cases were significantly younger than cases
infected by HPV16 (mean age: 43.3, 44.4, 50.5 years, respectively). A routine
cervical cancer screening and HPV vaccination program does not yet exist in
Pakistan; however, the country could benefit from national integrated efforts for
cervical cancer prevention and control. Calculated estimations based on our
results show that current HPV vaccine could potentially prevent new ICC cases.
PMID- 27483323
TI - The Balance between Recombination Enzymes and Accessory Replicative Helicases in
Facilitating Genome Duplication.
AB - Accessory replicative helicases aid the primary replicative helicase in
duplicating protein-bound DNA, especially transcribed DNA. Recombination enzymes
also aid genome duplication by facilitating the repair of DNA lesions via strand
exchange and also processing of blocked fork DNA to generate structures onto
which the replisome can be reloaded. There is significant interplay between
accessory helicases and recombination enzymes in both bacteria and lower
eukaryotes but how these replication repair systems interact to ensure efficient
genome duplication remains unclear. Here, we demonstrate that the DNA content
defects of Escherichia coli cells lacking the strand exchange protein RecA are
driven primarily by conflicts between replication and transcription, as is the
case in cells lacking the accessory helicase Rep. However, in contrast to Rep,
neither RecA nor RecBCD, the helicase/exonuclease that loads RecA onto dsDNA
ends, is important for maintaining rapid chromosome duplication. Furthermore,
RecA and RecBCD together can sustain viability in the absence of accessory
replicative helicases but only when transcriptional barriers to replication are
suppressed by an RNA polymerase mutation. Our data indicate that the minimisation
of replisome pausing by accessory helicases has a more significant impact on
successful completion of chromosome duplication than recombination-directed fork
repair.
PMID- 27483325
TI - Deliberate Establishment of Asymptomatic Bacteriuria-A Novel Strategy to Prevent
Recurrent UTI.
AB - We have established a novel strategy to reduce the risk for recurrent urinary
tract infection (UTI), where rapidly increasing antibiotic resistance poses a
major threat. Epidemiologic studies have demonstrated that asymptomatic
bacteriuria (ABU) protects the host against symptomatic infections with more
virulent strains. To mimic this protective effect, we deliberately establish ABU
in UTI-prone patients, who are refractory to conventional therapy. The patients
are inoculated with Escherichia coli (E. coli) 83972, now widely used as a
prototype ABU strain. Therapeutic efficacy has been demonstrated in a placebo
controlled trial, supporting the feasibility of using E. coli 83972 as a tool to
prevent recurrent UTI and, potentially, to outcompete antibiotic-resistant
strains from the human urinary tract. In addition, the human inoculation protocol
offers unique opportunities to study host-parasite interaction in vivo in the
human urinary tract. Here, we review the clinical evidence for protection using
this approach as well as some molecular insights into the pathogenesis of UTI
that have been gained during these studies.
PMID- 27483324
TI - Telomerase: The Devil Inside.
AB - High telomerase activity is detected in nearly all human cancers but most human
cells are devoid of telomerase activity. There is well-documented evidence that
reactivation of telomerase occurs during cellular transformation. In humans,
tumors can rely in reactivation of telomerase or originate in a telomerase
positive stem/progenitor cell, or rely in alternative lengthening of telomeres, a
telomerase-independent telomere-length maintenance mechanism. In this review, we
will focus on the telomerase positive tumors. In this context, the recent
findings that telomerase reverse transcriptase (TERT) promoter mutations
represent the most common non-coding mutations in human cancer have flared up the
long-standing discussion whether cancer originates from telomerase positive stem
cells or telomerase reactivation is a final step in cellular transformation.
Here, we will discuss the pros and cons of both concepts in the context of
telomere length-dependent and telomere length-independent functions of
telomerase. Together, these observations may provoke a re-evaluation of telomere
and telomerase based therapies, both in telomerase inhibition for cancer therapy
and telomerase activation for tissue regeneration and anti-ageing strategies.
PMID- 27483326
TI - The Impact of Rendered Protein Meal Oxidation Level on Shelf-Life, Sensory
Characteristics, and Acceptability in Extruded Pet Food.
AB - Pet foods are expected to have a shelf-life for 12 months or more. Sensory
analysis can be used to determine changes in products and to estimate products'
shelf-life. The objectives of this study were to (1) investigate how increasing
levels of oxidation in rendered protein meals used to produce extruded pet food
affected the sensory properties and (2) determine the effect of shelf-life on pet
owners' acceptability of extruded pet food diet formulated without the use of
preservative. Pet food diets contained beef meat bone meal (BMBM) and chicken
byproduct meal (CBPM) in which the oxidation was retarded with ethoxyquin, mixed
tocopherols, or none at all, and then extruded into dry pet foods. These samples
represented low, medium, and high oxidation levels, respectively. Samples were
stored for 0, 3, 6, 9, and 12 months at ambient temperature. Each time point,
samples were evaluated by six highly trained descriptive panelists for sensory
attributes related to oxidation. Samples without preservatives were chosen for
the acceptability test, since the differences in sensory characteristics over
storage time were more distinguishable in those samples. Pet owners evaluated
samples for aroma, appearance and overall liking. Descriptive sensory analysis
detected significant changes in oxidized-related sensory characteristics over
storage time. However, the differences for CBPM samples were more pronounced and
directional. The consumer study showed no differences in pet owners'
acceptability for BMBM samples. However, the noticeable increase in aroma
characteristics (rancid aroma 0.33-4.21) in CBPM samples over storage time did
have a negative effect on consumer's liking (overall liking 5.52-4.95).
PMID- 27483327
TI - Combining Coagulation/MIEX with Biological Activated Carbon Treatment to Control
Organic Fouling in the Microfiltration of Secondary Effluent.
AB - Coagulation, magnetic ion exchange resin (MIEX) and biological activated carbon
(BAC) were examined at lab scale as standalone, and sequential pre-treatments for
controlling the organic fouling of a microfiltration membrane by biologically
treated secondary effluent (BTSE) using a multi-cycle approach. MIEX gave
slightly greater enhancement in flux than coagulation due to greater removal of
high molecular weight (MW) humic substances, although it was unable to remove
high MW biopolymers. BAC treatment was considerably more effective for improving
the flux than coagulation or MIEX. This was due to the biodegradation of
biopolymers and/or their adsorption by the biofilm, and adsorption of humic
substances by the activated carbon, as indicated by size exclusion
chromatography. Coagulation or MIEX followed by BAC treatment further reduced the
problematic foulants and significantly improved the flux performance. The unified
membrane fouling index showed that the reduction of membrane fouling by
standalone BAC treatment was 42%. This improved to 65%, 70%, and 93% for alum,
ferric chloride and MIEX pre-treatment, respectively, when followed by BAC
treatment. This study showed the potential of sequential MIEX and BAC pre
treatment for controlling organic fouling and thus enhancing the performance of
microfiltration in the reclamation of BTSE.
PMID- 27483329
TI - Effects of Cardiorespiratory Fitness and Obesity on Salivary Secretory IgA and
Alpha-Amylase in South African Children.
AB - This study examined whether cardiorespiratory fitness (CRF) and body composition
are associated with salivary secretory immunoglobulin A (SIgA), a mucosal
immunity marker, and salivary alpha-amylase (sAA), a marker of stress-related
sympathetic nervous system (SNS) activity, in South African children. Morning
(7:30-8:00 a.m.) saliva samples were collected from 132 children (10.05 +/- 1.68
years old, 74 females, 58 males). Body composition, resting blood pressure, and
predicted maximal aerobic capacity (VO2max) were determined, and SIgA and sAA
were quantified. Obese children had significantly higher sAA compared with
overweight and normal weight children (p < 0.01). SIgA secretion rate was
significantly lower in obese and overweight vs. normal weight children (p <
0.01). Multiple-linear regression analysis revealed that body mass index (BMI) (p
< 0.05) and diastolic blood pressure (DBP) (p < 0.05) were independent predictors
of sAA with CRF acting as a mitigator. Age and BMI predicted SIgA secretion rate
(p < 0.05) with BMI (p < 0.001) found to be an independent predictor of SIgA
secretion rate. Obesity, based on BMI, was associated with elevated SNS activity
and lowered mucosal immunity. CRF-mitigated sympathetic activation was not
associated with mucosal immunity.
PMID- 27483330
TI - Fluorene-Perylene Diimide Arrays onto Graphene Sheets for Photocatalysis.
AB - A facile approach for introducing photoactive poly(fluorene-perylene diimide)
arrays (PFPDI) onto graphene sheets was accomplished. Noncovalent PFPDI/graphene
ensembles formed via pi-pi stacking interactions between the two components and
covalent PFPDI-graphene hybrids realized upon a Stille polycondensation reaction
between an iodobenzyl-functionalized graphene, a 9,9-dialkyl substituted fluorene
diboronic acid, and a 1,7-dibromo-PDI derivative were prepared. The morphology of
PFPDI/graphene and PFPDI-graphene was evaluated by high-resolution transmission
electron microscopy (HR-TEM), revealing the presence of even monolayered graphene
sheets. Moreover, their photophysical and redox properties as assessed by
electronic absorption spectroscopy and steady-state as well as time-resolved
photoluminescence assays and electrochemistry, respectively, disclosed charge
transfer characteristics owing to the high photoluminescence quenching of PFPDI
in the presence of graphene and the fast component attributed to the decay of the
emission intensity of the singlet excited state of PFPDI in both PFPDI/graphene
and PFPDI-graphene. Next, testing their ability to operate in energy conversion
schemes, the PFPDI-graphene was successfully employed as catalyst for the
reduction of 4-nitrophenol to 4-aminophenol. Notably, the kinetics for the
reduction were enhanced by visible light photoirradiation as compared to dark
conditions as well as the presence of PFPDI-graphene, contrasting the case where
only PFPDI, in the absence of graphene, was employed. Finally, recycling of the
catalyst PFPDI-graphene was achieved and reutilization in successive reduction
reactions of 4-nitrophenol was found to proceed with the same efficiency.
PMID- 27483328
TI - Functional Consequences of Differential O-glycosylation of MUC1, MUC4, and MUC16
(Downstream Effects on Signaling).
AB - Glycosylation is one of the most abundant post-translational modifications that
occur within the cell. Under normal physiological conditions, O-linked
glycosylation of extracellular proteins is critical for both structure and
function. During the progression of cancer, however, the expression of aberrant
and truncated glycans is commonly observed. Mucins are high molecular weight
glycoproteins that contain numerous sites of O-glycosylation within their
extracellular domains. Transmembrane mucins also play a functional role in
monitoring the surrounding microenvironment and transducing these signals into
the cell. In cancer, these mucins often take on an oncogenic role and promote a
number of pro-tumorigenic effects, including pro-survival, migratory, and
invasive behaviors. Within this review, we highlight both the processes involved
in the expression of aberrant glycan structures on mucins, as well as the
potential downstream impacts on cellular signaling.
PMID- 27483331
TI - Vision-related Quality of Life in Glaucoma Suspect or Early Glaucoma Patients.
AB - PURPOSE: To determine the association of vision-related quality of life (QoL) to
demographic factors and visual function in glaucoma suspect or early glaucoma
patients. MATERIALS AND METHODS: We administered the 25-item National Eye
Institute Visual Function Questionnaire (VFQ-25) on the same day as a
comprehensive ocular examination to participants either with glaucoma or at high
risk for developing glaucoma. Regression models were used to determine the
association between VFQ-25 composite and subscale scores, visual field status,
logMAR equivalent visual acuity (VA), age, and sex. In all analyses we used data
from the eye with the best mean deviation (MD), best pattern SD, and best VA.
RESULTS: Data from 198 participants were analyzed. The mean best MD (+/-SD) was
0.02+/-1.52 dB (range, -5.11 to 2.63 dB) and the mean best pattern SD was 1.75+/
1.03 dB (range, 0.91 to 8.36 dB). The mean VFQ-25 composite score was 91.6+/-6.7
(range, 54.5 to 100.0). Composite score and the Distance Activities, Color Vision
subscale scores were associated with best MD (P<=0.05). The General Vision and
Driving subscale scores were associated with best VA (P<=0.03). The composite
score and the Distance Activities, Driving, and Color Vision subscale scores were
associated with age (P<=0.05). Finally, the Distance Activities, Driving, and
Peripheral Vision subscale scores were associated with sex (P<=0.04).
CONCLUSIONS: Vision-related QoL is associated with visual field status even in
early and suspected glaucoma. It is also associated with VA, age, and sex.
Particular decreases in QoL are related to distance activities, driving, and
color vision.
PMID- 27483332
TI - Spontaneous Resolution of Presumed Idiopathic Elevated Episcleral Venous
Pressure.
AB - PURPOSE: To report a case of presumed idiopathic elevated episcleral venous
pressure (EVP) initially requiring medical management. METHODS: We present a case
report of a 28-year-old white man presenting with eye redness and soreness as a
referral to the glaucoma service. He was diagnosed with idiopathic elevated EVP
after systematic workup. RESULTS: Unilateral elevated intraocular pressure was
detected along with dilated episcleral vessels, mild cupping of optic nerve head,
and blood in Schlemm's canal, yet negative angiographic imaging and
hypercoagulable labs. Topical antiglaucoma medication normalized intraocular
pressure, which then maintained with resolution of episcleral vessel caliper and
blood in Schlemm's canal after discontinuation of medication. CONCLUSIONS: This
is the first reported case of spontaneous resolution of presumed idiopathic
elevated EVP, persisting after discontinuation of medical therapy and without
surgical intervention.
PMID- 27483333
TI - New Ultrasound Biomicroscopy Iris Findings in Juvenile Xanthogranuloma.
AB - We report a case of juvenile xanthogranuloma in a 12-month-old girl presenting
with heterochromia, hyphema, and elevated intraocular pressure. This case
demonstrates new ultrasound biomicroscopy iris findings of a generalized bumpy
iris contour, suggesting diffuse heterogeneous involvement. This imaging finding
has not been previously described. Untreated, iris juvenile xanthogranuloma may
lead to corneal blood staining, glaucoma, and amblyopia. An understanding of the
full range of ultrasound features of juvenile xanthogranuloma expands our
appreciation for the clinical findings in this condition.
PMID- 27483334
TI - Gas-Phase Interaction of Anions with Polyisobutylenes: Collision-Induced
Dissociation Study and Quantum Chemical Modeling.
AB - The gas-phase interaction of anions including fluoride, chloride, bromide,
iodide, ethyl sulfate, chlorate, and nitrate with polyisobutylene (PIB)
derivatives was studied using collision-induced dissociation (CID). The gas-phase
adducts of anions with PIBs ([PIB + anion](-)) were generated from the
electrosprayed solution of PIBs in the presence of the corresponding anions. The
so-formed adducts subjected to CID showed a loss of anion at different
characteristic collision energies, thus allowing the study of the strength of
interaction between the anions and nonpolar PIBs having different end-groups. The
values of characteristic collision energies (the energy needed to obtain 50%
fragmentation) obtained by CID experiments correlated linearly with the binding
enthalpies between the anion and PIB, as determined by density functional theory
calculations. In the case of halide ions, the critical energies for dissociation,
that is, the binding enthalpies for [PIB + anion](-) adducts, increased in the
order of I(-) < Br(-) < Cl(-) < F(-). Furthermore, it was found that the binding
enthalpies for the adducts formed with halide ions decreased approximately with
the square radius of the halide ion, suggesting that the strength of interaction
is mainly determined by the "surface" charge density of the halide ion. In
addition, the characteristic collision energy versus the number of isobutylene
units revealed a linear dependence.
PMID- 27483335
TI - Work Characteristics as Predictors of Correctional Supervisors' Health Outcomes.
AB - OBJECTIVE: This study examined associations among health behaviors, psychosocial
work factors, and health status. METHODS: Correctional supervisors (n = 157)
completed a survey that assessed interpersonal and organizational views on
health. Chi-square and logistic regressions were used to examine relationships
among variables. RESULTS: Respondents had a higher prevalence of obesity and
comorbidities compared with the general US adult population. Burnout was
significantly associated with nutrition, physical activity, sleep duration, sleep
quality, diabetes, and anxiety/depression. Job meaning, job satisfaction, and
workplace social support may predict health behaviors and outcomes. CONCLUSIONS:
Correctional supervisors are understudied and have poor overall health status.
Improving health behaviors of middle-management employees may have a beneficial
effect on the health of the entire workforce. This paper demonstrates the
importance of psychosocial work factors that may contribute to health behaviors
and outcomes.
PMID- 27483336
TI - Air Pollution During Pregnancy and Cord Blood Immune System Biomarkers.
AB - OBJECTIVES: We aimed to determine whether average and trimester-specific
exposures to ambient measures of nitrogen dioxide (NO2) and particular matter
(PM2.5) were associated with elevated cord blood concentrations of immunoglobulin
E (IgE) and two epithelial cell produced cytokines: interleukin-33 (IL-33) and
thymic stromal lymphopoietin (TSLP). METHODS: This study utilized data and
biospecimens from the Maternal-Infant Research on Environmental Chemicals (MIREC)
Study. There were 2001 pregnant women recruited between 2008 and 2011 from 10
Canadian cities. Maternal exposure to NO2 and PM2.5 was estimated using land use
regression and satellite-derived models. RESULTS: We observed statistically
significant associations between maternal NO2 exposure and elevated cord blood
concentrations of both IL-33 and TSLP among girls but not boys. CONCLUSIONS:
Maternal NO2 exposure may impact the development of the newborn immune system as
measured by cord blood concentrations of two cytokines.
PMID- 27483338
TI - Transmission electron microscopy of carbon-coated and iron-doped titania
nanoparticles.
AB - We present a study on the properties of iron (Fe)-doped and carbon (C)-coated
titania (TiO2) nanoparticles (NPs) which has been compiled by using x-ray
diffraction (XRD), transmission electron microscopy (TEM), and x-ray
photoelectron spectroscopy (XPS). These TiO2 NPs were prepared by using the flame
synthesis method. This method allows the simultaneous C coating and Fe doping of
TiO2 NPs. XRD investigations revealed that the phase of the prepared NPs was
anatase TiO2. Conventional TEM analysis showed that the average size of the TiO2
NPs was about 65 nm and that the NPs were uniformly coated with the element C.
Furthermore, from the x-ray energy dispersive spectrometry analysis, it was found
that about 8 at.% Fe was present in the synthesized samples. High-resolution TEM
(HRTEM) revealed the graphitized carbon structure of the layer surrounding the
prepared TiO2 NPs. HRTEM analysis further revealed that the NPs possessed the
crystalline structure of anatase titania. Energy-filtered TEM (EFTEM) analysis
showed the C coating and Fe doping of the NPs. The ratio of L3 and L2 peaks for
the Ti-L23 and Fe-L23 edges present in the core loss electron energy loss
spectroscopy (EELS) revealed a +4 oxidation state for the Ti and a +3 oxidation
state for the Fe. These EELS results were further confirmed with XPS analysis.
The electronic properties of the samples were investigated by applying Kramers
Kronig analysis to the low-loss EELS spectra acquired from the prepared NPs. The
presented results showed that the band gap energy of the TiO2 NPs decreased from
an original value of 3.2 eV to about 2.2 eV, which is quite close to the ideal
band gap energy of 1.65 eV for photocatalysis semiconductors. The observed
decrease in band gap energy of the TiO2 NPs was attributed to the presence of Fe
atoms at the lattice sites of the anatase TiO2 lattice. In short, C-coated and Fe
doped TiO2 NPs were synthesized with a rather cost-effective and comparatively
easily scalable method. The presented analysis enables us to predict the
excellent efficiency of these NPs for solar-cell and photo-catalysis
applications.
PMID- 27483337
TI - Chronic Condition Combinations and Productivity Loss Among Employed Nonelderly
Adults (18 to 64 Years).
AB - OBJECTIVE: We examined the relationship between specific chronic condition
combinations and productivity loss measured by missed work days among nonelderly
employed adults with at least two physical chronic conditions of arthritis,
diabetes mellitus, heart disease, and hypertension. METHODS: We analyzed data
from the Medical Expenditure Panel Survey for the years 2004 to 2012. RESULTS:
Adults with arthritis/diabetes/heart disease had the highest average missed work
days (14.42). In the adjusted model, compared with adults with
arthritis/hypertension, adults with diabetes/heart disease and arthritis/heart
disease/hypertension had significantly higher missed work days, while adults with
diabetes/hypertension had significantly lower missed work days. CONCLUSION:
Specific chronic condition combinations have a high burden of disease in terms of
productivity loss. Workplace health programs that address multiple health
conditions at the same time should be implemented to reduce missed work days.
PMID- 27483339
TI - Accelerating Drug Development: Antiviral Therapies for Emerging Viruses as a
Model.
AB - Drug discovery and development is a lengthy and expensive process. Although no
one, simple, single solution can significantly accelerate this process, steps can
be taken to avoid unnecessary delays. Using the development of antiviral
therapies as a model, we describe options for acceleration that cover target
selection, assay development and high-throughput screening, hit confirmation,
lead identification and development, animal model evaluations, toxicity studies,
regulatory issues, and the general drug discovery and development infrastructure.
Together, these steps could result in accelerated timelines for bringing
antiviral therapies to market so they can treat emerging infections and reduce
human suffering.
PMID- 27483340
TI - A Life of Neurotransmitters.
AB - Development of scientific creativity is often tied closely to mentorship. In my
case, two years with Julius Axelrod, the sum total of my research training, was
transformative. My mentoring generations of graduate students and postdoctoral
fellows has been as nurturing for me as it has been for them. Work in our lab
over fifty years has covered the breadth of neurotransmitters and related
substances, focusing on the discovery and characterization of novel messenger
molecules. I can't conceptualize a more rewarding professional life.
PMID- 27483341
TI - Single-Photon Emission Computed Tomography/Computed Tomography Imaging in a
Rabbit Model of Emphysema Reveals Ongoing Apoptosis In Vivo.
AB - Evaluation of lung disease is limited by the inability to visualize ongoing
pathological processes. Molecular imaging that targets cellular processes related
to disease pathogenesis has the potential to assess disease activity over time to
allow intervention before lung destruction. Because apoptosis is a critical
component of lung damage in emphysema, a functional imaging approach was taken to
determine if targeting apoptosis in a smoke exposure model would allow the
quantification of early lung damage in vivo. Rabbits were exposed to cigarette
smoke for 4 or 16 weeks and underwent single-photon emission computed
tomography/computed tomography scanning using technetium-99m-rhAnnexin V-128.
Imaging results were correlated with ex vivo tissue analysis to validate the
presence of lung destruction and apoptosis. Lung computed tomography scans of
long-term smoke-exposed rabbits exhibit anatomical similarities to human
emphysema, with increased lung volumes compared with controls. Morphometry on
lung tissue confirmed increased mean linear intercept and destructive index at 16
weeks of smoke exposure and compliance measurements documented physiological
changes of emphysema. Tissue and lavage analysis displayed the hallmarks of smoke
exposure, including increased tissue cellularity and protease activity.
Technetium-99m-rhAnnexin V-128 single-photon emission computed tomography signal
was increased after smoke exposure at 4 and 16 weeks, with confirmation of
increased apoptosis through terminal deoxynucleotidyl transferase dUTP nick end
labeling staining and increased tissue neutral sphingomyelinase activity in the
tissue. These studies not only describe a novel emphysema model for use with
future therapeutic applications, but, most importantly, also characterize a
promising imaging modality that identifies ongoing destructive cellular processes
within the lung.
PMID- 27483342
TI - Multidrug-Resistant Aeromonas veronii Recovered from Channel Catfish (Ictalurus
punctatus) in China: Prevalence and Mechanisms of Fluoroquinolone Resistance.
AB - To emphasize the importance of the appropriate use of antibiotics in aquaculture
systems, the prevalence of resistance to 25 antimicrobials was investigated in 42
Aeromonas veronii strains isolated from farm-raised channel catfish in China in
2006-2012. All experiments were based on minimal inhibitory concentrations
(MICs), and susceptibility was assessed according to the Clinical and Laboratory
Standards Institute. Some isolates displayed antibiotic resistance to the latest
generation fluoroquinolones (i.e., ciprofloxacin, levofloxacin, and norfloxacin)
in vitro. Therefore, we screened for genes conferring resistance to
fluoroquinolones and performed conjugation experiments to establish the
resistance mechanisms. The antibiotic resistance rates were 14.29-21.42% to three
kinds of fluoroquinolones: ciprofloxacin, levofloxacin, and norfloxacin. Among
the 42 strains isolated, 15 carried the qnrS2 gene. The MICs of the
fluoroquinolones in transconjugants with qnrS2 were more than fourfold higher
compared with the recipient. Among the fluoroquinolone-resistant A. veronii
strains, eight had point mutations in both gyrA codon 83 (Ser83->Ile83) and parC
codon 87 (Ser87->Ile87). However, five isolates with point mutations in parC
codon 52 remained susceptible to the three fluoroquinolones. In conclusion, the
mechanisms of fluoroquinolone resistance in A. veronii isolates may be related to
mutations in gyrA codon 83 and parC codon 87 and the presence of the qnrS2 gene.
PMID- 27483343
TI - The SMAD Pathway Is Required for Hepcidin Response During Endoplasmic Reticulum
Stress.
AB - Hepcidin, the iron hormone, is regulated by a number of stimulatory and
inhibitory signals. The cAMP responsive element binding protein 3-like 3
(CREB3L3) mediates hepcidin response to endoplasmic reticulum (ER) stress. In
this study we asked whether hepcidin response to ER stress also requires the
small mother against decapentaplegic (SMAD)-1/5/8 pathway, which has a major role
in hepcidin regulation in response to iron and other stimuli. We analyzed
hepcidin mRNA expression and promoter activity in response to ER stressors in
HepG2 cells in the presence of the bone morphogenetic protein (BMP) type I
receptor inhibitor LDN-193189, mutated hepcidin promoter or small interfering RNA
against different SMAD proteins. We then used a similar approach in vivo in wild
type, Smad1/5, or Creb3l3-/- animals undergoing ER stress. In vitro, LDN-193189
prevented hepcidin mRNA induction by different ER stressors. Seemingly, mutation
of a BMP-responsive element in the hepcidin promoter prevented ER stress-mediated
up-regulation. Moreover, in vitro silencing of SMAD proteins by small interfering
RNA, in particular SMAD5, blunted hepcidin response to ER stress. On the
contrary, hepcidin induction by ER stress was maintained when using antibodies
against canonical BMP receptor ligands. In vivo, hepcidin was induced by ER
stress and prevented by LDN-193189. In addition, in Smad1/5 knockout mice, ER
stress was unable to induce hepcidin expression. Finally, in Creb3l3 knockout
mice, in response to ER stress, SMAD1/5 were correctly phosphorylated and
hepcidin induction was still appreciable, although to a lesser extent as compared
with the control mice. In conclusion, our study indicates that hepcidin induction
by ER stress involves the central regulatory SMAD1/5 pathway.
PMID- 27483344
TI - Correlation between afferent rearrangements and behavioral deficits after local
excitotoxic insult in the mammalian vestibule: a rat model of vertigo symptoms.
AB - Damage to inner ear afferent terminals is believed to result in many auditory and
vestibular dysfunctions. The sequence of afferent injuries and repair, as well as
their correlation with vertigo symptoms, remains poorly documented. In
particular, information on the changes that take place at the primary vestibular
endings during the first hours following a selective insult is lacking. In the
present study, we combined histological analysis with behavioral assessments of
vestibular function in a rat model of unilateral vestibular excitotoxic insult.
Excitotoxicity resulted in an immediate but transient alteration of the balance
function that was resolved within a week. Concomitantly, vestibular primary
afferents underwent a sequence of structural changes followed by spontaneous
repair. Within the first two hours after the insult, a first phase of pronounced
vestibular dysfunction coincided with extensive swelling of afferent terminals.
In the next 24 h, a second phase of significant but incomplete reduction of the
vestibular dysfunction was accompanied by a resorption of swollen terminals and
fiber retraction. Eventually, within 1 week, a third phase of complete balance
restoration occurred. The slow and progressive withdrawal of the balance
dysfunction correlated with full reconstitution of nerve terminals. Competitive
re-innervation by afferent and efferent terminals that mimicked developmental
synaptogenesis resulted in full re-afferentation of the sensory epithelia. By
deciphering the sequence of structural alterations that occur in the vestibule
during selective excitotoxic impairment, this study offers new understanding of
how a vestibular insult develops in the vestibule and how it governs the
heterogeneity of vertigo symptoms.
PMID- 27483345
TI - The role of the dopamine D1 receptor in social cognition: studies using a novel
genetic rat model.
AB - Social cognition is an endophenotype that is impaired in schizophrenia and
several other (comorbid) psychiatric disorders. One of the modulators of social
cognition is dopamine, but its role is not clear. The effects of dopamine are
mediated through dopamine receptors, including the dopamine D1 receptor (Drd1).
Because current Drd1 receptor agonists are not Drd1 selective, pharmacological
tools are not sufficient to delineate the role of the Drd1. Here, we describe a
novel rat model with a genetic mutation in Drd1 in which we measured basic
behavioural phenotypes and social cognition. The I116S mutation was predicted to
render the receptor less stable. In line with this computational prediction, this
Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1
expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to
decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic
motoric and neurological parameters, as well as locomotor activity and anxiety
like behaviour. However, measures of social cognition like social interaction,
scent marking, pup ultrasonic vocalizations and sociability, were strongly
reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field
of neuroscience a novel genetic rat model to study a series of psychiatric
disorders including schizophrenia, autism, depression, bipolar disorder and drug
addiction.
PMID- 27483346
TI - Nicotine ameliorates schizophrenia-like cognitive deficits induced by maternal
LPS exposure: a study in rats.
AB - Maternal exposure to infectious agents is a predisposing factor for schizophrenia
with associated cognitive deficits in offspring. A high incidence of smoking in
these individuals in adulthood might be, at least in part, due to the cognitive
enhancing effects of nicotine. Here, we have used prenatal exposure to maternal
lipopolysaccharide (LPS, bacterial endotoxin) at different time points as a model
for cognitive deficits in schizophrenia to determine whether nicotine reverses
any associated impairments. Pregnant rats were treated subcutaneously with LPS
(0.5 mg/kg) at one of three neurodevelopmental time periods [gestation days (GD)
10-11, 15-16, 18-19]. Cognitive assessment in male offspring commenced in early
adulthood [postnatal day (PND) 60] and included: prepulse inhibition (PPI),
latent inhibition (LI) and delayed non-matching to sample (DNMTS). Following PND
100, daily nicotine injections (0.6 mg/kg, subcutaneously) were administered, and
animals were re-tested in the same tasks (PND 110). Only maternal LPS exposure
early during fetal neurodevelopment (GD 10-11) resulted in deficits in all tests
compared to animals that had been prenatally exposed to saline at the same
gestational time point. Repeated nicotine treatment led to global (PPI) and
selective (LI) improvements in performance. Early but not later prenatal LPS
exposure induced consistent deficits in cognitive tests with relevance for
schizophrenia. Nicotine reversed the LPS-induced deficits in selective attention
(LI) and induced a global enhancement of sensorimotor gating (PPI).
PMID- 27483347
TI - Increased trabecular bone and improved biomechanics in an osteocalcin-null rat
model created by CRISPR/Cas9 technology.
AB - Osteocalcin, also known as bone gamma-carboxyglutamate protein (Bglap), is
expressed by osteoblasts and is commonly used as a clinical marker of bone
turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a
mediator of changes to the skeleton, endocrine system, reproductive organs and
central nervous system. However, differences between mouse and human osteocalcin
at both the genome and protein levels have challenged the validity of
extrapolating findings from the osteocalcin-deficient mouse model to human
disease. The rat osteocalcin (Bglap) gene locus shares greater synteny with that
of humans. To further examine the role of osteocalcin in disease, we created a
rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat
osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of
fertilized single cell Sprague-Dawley embryos, and animals were bred to
homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X
ray absorptiometry (DXA), glucose tolerance testing (GTT), insulin tolerance
testing (ITT), microcomputed tomography (uCT), and a three-point break
biomechanical assay were performed on the excised femurs at 5 months of age.
Complete loss of osteocalcin resulted in bones with significantly increased
trabecular thickness, density and volume. Cortical bone volume and density were
not increased in null animals. The bones had improved functional quality as
evidenced by an increase in failure load during the biomechanical stress assay.
Differences in glucose homeostasis were observed between groups, but there were
no differences in body weight or composition. This rat model of complete loss of
osteocalcin provides a platform for further understanding the role of osteocalcin
in disease, and it is a novel model of increased bone formation with potential
utility in osteoporosis and osteoarthritis research.
PMID- 27483348
TI - Identification of a nutrient-sensing transcriptional network in monocytes by
using inbred rat models on a cafeteria diet.
AB - Obesity has reached pandemic levels worldwide. The current models of diet-induced
obesity in rodents use predominantly high-fat based diets that do not take into
account the consumption of variety of highly palatable, energy-dense foods that
are prevalent in Western society. We and others have shown that the cafeteria
(CAF) diet is a robust and reproducible model of human metabolic syndrome with
tissue inflammation in the rat. We have previously shown that inbred rat strains
such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF
diets with distinct metabolic and morphometric profiles. Here, we show a
difference in plasma MCP-1 levels and investigate the effect of the CAF diet on
peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells,
in WKY and LEW rats. We found that 75.5% of the differentially expressed
transcripts under the CAF diet were upregulated in WKY rats and were functionally
related to the activation of the immune response. Using a gene co-expression
network constructed from the genes differentially expressed between CAF diet-fed
LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2
(Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes.
The Acss2 genomic region is significantly enriched for previously established
metabolism quantitative trait loci in the rat. Notably, monocyte expression
levels of Acss2 significantly correlated with plasma glucose, triglyceride,
leptin and non-esterified fatty acid (NEFA) levels as well as morphometric
measurements such as body weight and the total fat following feeding with the CAF
diet in the rat. These results show the importance of the genetic background in
nutritional genomics and identify inbred rat strains as potential models for CAF
diet-induced obesity.
PMID- 27483349
TI - Conditional deletion of AP-2beta in mouse cranial neural crest results in
anterior segment dysgenesis and early-onset glaucoma.
AB - Anterior segment dysgenesis (ASD) encompasses a group of developmental disorders
in which a closed angle phenotype in the anterior chamber of the eye can occur
and 50% of patients develop glaucoma. Many ASDs are thought to involve an
inappropriate patterning and migration of the periocular mesenchyme (POM), which
is derived from cranial neural crest cells (NCCs) and mesoderm. Although, the
mechanism of this disruption is not well understood, a number of transcriptional
regulatory molecules have previously been implicated in ASDs. Here, we
investigate the function of the transcription factor AP-2beta, encoded by Tfap2b,
which is expressed in NCCs and their derivatives. Wnt1-Cre-mediated conditional
deletion of Tfap2b in NCCs resulted in post-natal ocular defects typified by
opacity. Histological data revealed that the conditional AP-2beta NCC knockout
(KO) mutants exhibited dysgenesis of multiple structures in the anterior segment
of the eye including defects in the corneal endothelium, corneal stroma, ciliary
body and disruption in the iridocorneal angle with adherence of the iris to the
cornea. We further show that this phenotype leads to a significant increase in
intraocular pressure and a subsequent loss of retinal ganglion cells and optic
nerve degeneration, features indicative of glaucoma. Overall, our findings
demonstrate that AP-2beta is required in the POM for normal development of the
anterior segment of the eye and that the AP-2beta NCC KO mice might serve as a
new and exciting model of ASD and glaucoma that is fully penetrant and with early
post-natal onset.
PMID- 27483350
TI - A rat model for hepatitis E virus.
AB - Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and
chronic hepatitis E is increasingly recognized as an important problem in the
transplant setting. Nevertheless, the fundamental understanding of the biology of
HEV replication is limited and there are few therapeutic options. The development
of such therapies is partially hindered by the lack of a robust and convenient
animal model. We propose the infection of athymic nude rats with the rat HEV
strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the
infectivity of its capped RNA transcripts was confirmed in vitro and in vivo
Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated
for in vitro antiviral studies. Interestingly, rat HEV proved to be less
sensitive to the antiviral activity of alpha-interferon, ribavirin and
mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof
of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was
swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon
replicated with comparable efficiency as the wild-type construct, confirming that
LA-B350 strain is amenable to humanization (replacement of certain sequences or
motifs by their counterparts from human HEV strains). Finally, ribavirin
effectively inhibited LA-B350 replication in athymic nude rats, confirming the
suitability of the rat model for antiviral studies.
PMID- 27483351
TI - MicroRNA screening identifies a link between NOVA1 expression and a low level of
IKAP in familial dysautonomia.
AB - Familial dysautonomia (FD) is a rare neurodegenerative disease caused by a
mutation in intron 20 of the IKBKAP gene (c.2204+6T>C), leading to tissue
specific skipping of exon 20 and a decrease in the synthesis of the encoded
protein IKAP (also known as ELP1). Small non-coding RNAs known as microRNAs
(miRNAs) are important post-transcriptional regulators of gene expression and
play an essential role in the nervous system development and function. To better
understand the neuronal specificity of IKAP loss, we examined expression of
miRNAs in human olfactory ecto-mesenchymal stem cells (hOE-MSCs) from five
control individuals and five FD patients. We profiled the expression of 373
miRNAs using microfluidics and reverse transcription coupled to quantitative PCR
(RT-qPCR) on two biological replicate series of hOE-MSC cultures from healthy
controls and FD patients. This led to the total identification of 26 dysregulated
miRNAs in FD, validating the existence of a miRNA signature in FD. We then
selected the nine most discriminant miRNAs for further analysis. The signaling
pathways affected by these dysregulated miRNAs were largely within the nervous
system. In addition, many targets of these dysregulated miRNAs had been
previously demonstrated to be affected in FD models. Moreover, we found that four
of our nine candidate miRNAs target the neuron-specific splicing factor NOVA1. We
demonstrated that overexpression of miR-203a-3p leads to a decrease of NOVA1,
counter-balanced by an increase of IKAP, supporting a potential interaction
between NOVA1 and IKAP. Taken together, these results reinforce the choice of
miRNAs as potential therapeutic targets and suggest that NOVA1 could be a
regulator of FD pathophysiology.
PMID- 27483352
TI - Autophagy resolves early retinal inflammation in Igf1-deficient mice.
AB - Insulin-like growth factor-1 (IGF-1) is a growth factor with differentiating,
anti-apoptotic and metabolic functions in the periphery, and anti-inflammatory
properties in the nervous system. Mice that have mutations in the Igf1 gene,
rendering the gene product inactive (Igf1(-/-)), present with age-related visual
loss accompanied by structural alterations in the first synapses of the retinal
pathway. Recent advances have revealed a crucial role of autophagy in immunity
and inflammation. Keeping in mind this close relationship, we aimed to decipher
these processes in the context of the defects that occur during ageing in the
retina of Igf1(-/-) mice. Tnfa and Il1b mRNAs, and phosphorylation of JNK and p38
MAPK were elevated in the retinas of 6- and 12-month old Igf1(-/-) mice compared
to those in age-matched Igf1(+/+) controls. In 6-month-old Igf1(-/-) retinas,
increased mRNA levels of the autophagy mediators Becn1, Atg9, Atg5 and Atg4,
decreased p62 (also known as SQSTM1) protein expression together with an
increased LC3-II:LC3-I ratio reflected active autophagic flux. However, in
retinas from 12-month-old Igf1(-/-) mice, Nlrp3 mRNA, processing of the IL1beta
pro-form and immunostaining of active caspase-1 were elevated compared to those
in age-matched Igf1(+/+) controls, suggesting activation of the inflammasome.
This effect concurred with accumulation of autophagosomes and decreased
autophagic flux in the retina. Microglia localization and status of activation in
the retinas of 12-month-old Igf1(+/+) and Igf1(-/-) mice, analyzed by
immunostaining of Cd11b and Iba-1, showed a specific distribution pattern in the
outer plexiform layer (OPL), inner plexiform layer (IPL) and inner nuclear layer
(INL), and revealed an increased number of activated microglia cells in the
retina of 12-month-old blind Igf1(-/-) mice. Moreover, reactive gliosis was
exclusively detected in the retinas from 12-month-old blind Igf1(-/-) mice. In
conclusion, this study provides new evidence in a mouse model of IGF-1 deficiency
that autophagy is an adaptive response that might confer protection against
persistent inflammation in the retina during ageing.
PMID- 27483353
TI - YBR/EiJ mice: a new model of glaucoma caused by genes on chromosomes 4 and 17.
AB - A variety of inherited animal models with different genetic causes and distinct
genetic backgrounds are needed to help dissect the complex genetic etiology of
glaucoma. The scarcity of such animal models has hampered progress in glaucoma
research. Here, we introduce a new inherited glaucoma model: the inbred mouse
strain YBR/EiJ (YBR). YBR mice develop a form of pigmentary glaucoma. They
exhibit a progressive age-related pigment-dispersing iris disease characterized
by iris stromal atrophy. Subsequently, these mice develop elevated intraocular
pressure (IOP) and glaucoma. Genetic mapping studies utilizing YBR as a glaucoma
susceptible strain and C57BL/6J as a glaucoma-resistant strain were performed to
identify genetic loci responsible for the iris disease and high IOP. A recessive
locus linked to Tyrp1(b) on chromosome 4 contributes to iris stromal atrophy and
high IOP. However, this is not the only important locus. A recessive locus on YBR
chromosome 17 causes high IOP independent of the iris stromal atrophy. In
specific eyes with high IOP caused by YBR chromosome 17, the drainage angle
(through which ocular fluid leaves the eye) is largely open. The YBR alleles of
genes on chromosomes 4 and 17 underlie the development of high IOP and glaucoma
but do so through independent mechanisms. Together, these two loci act in an
additive manner to increase the susceptibility of YBR mice to the development of
high IOP. The chromosome 17 locus is important not only because it causes IOP
elevation in mice with largely open drainage angles but also because it
exacerbates IOP elevation and glaucoma induced by pigment dispersion. Therefore,
YBR mice are a valuable resource for studying the genetic etiology of IOP
elevation and glaucoma, as well as for testing new treatments.
PMID- 27483355
TI - A chemical with proven clinical safety rescues Down-syndrome-related phenotypes
in through DYRK1A inhibition.
AB - DYRK1A is important in neuronal development and function, and its excessive
activity is considered a significant pathogenic factor in Down syndrome and
Alzheimer's disease. Thus, inhibition of DYRK1A has been suggested to be a new
strategy to modify the disease. Very few compounds, however, have been reported
to act as inhibitors, and their potential clinical uses require further
evaluation. Here, we newly identify CX-4945, the safety of which has been already
proven in the clinical setting, as a potent inhibitor of DYRK1A that acts in an
ATP-competitive manner. The inhibitory potency of CX-4945 on DYRK1A (IC50=6.8 nM)
in vitro was higher than that of harmine, INDY or proINDY, which are well-known
potent inhibitors of DYRK1A. CX-4945 effectively reverses the aberrant
phosphorylation of Tau, amyloid precursor protein (APP) and presenilin 1 (PS1) in
mammalian cells. To our surprise, feeding with CX-4945 significantly restored the
neurological and phenotypic defects induced by the overexpression of minibrain,
an ortholog of human DYRK1A, in the Drosophila model. Moreover, oral
administration of CX-4945 acutely suppressed Tau hyperphosphorylation in the
hippocampus of DYRK1A-overexpressing mice. Our research results demonstrate that
CX-4945 is a potent DYRK1A inhibitor and also suggest that it has therapeutic
potential for DYRK1A-associated diseases.
PMID- 27483354
TI - Alterations in nuclear structure promote lupus autoimmunity in a mouse model.
AB - Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the
development of autoantibodies that recognize components of the cell nucleus. The
vast majority of lupus research has focused on either the contributions of immune
cell dysfunction or the genetics of the disease. Because granulocytes isolated
from human SLE patients had alterations in neutrophil nuclear morphology that
resembled the Pelger-Huet anomaly, and had prominent mis-splicing of mRNA
encoding the nuclear membrane protein lamin B receptor (LBR), consistent with
their Pelger-Huet-like nuclear morphology, we used a novel mouse model system to
test the hypothesis that a disruption in the structure of the nucleus itself also
contributes to the development of lupus autoimmunity. The lupus-prone mouse
strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a
heterozygous autosomal dominant mutation in Lbr (B6.Lbr(ic/+)), and the
(NZW*B6.Lbr(ic))F1 offspring were evaluated for induction of lupus autoimmunity.
Only female (NZW*B6.Lbr(ic))F1 mice developed lupus autoimmunity, which included
splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by
immune complex deposition, and perivascular and tubule infiltration of
mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged
female MRL-Fas(lpr) mice, and were predominantly of the IgG2 subclasses. The anti
nuclear antibody staining profile of female (NZW*B6.Lbr(ic))F1 sera was complex,
and consisted of an anti-nuclear membrane reactivity that colocalized with the A
type lamina, in combination with a homogeneous pattern that was related to the
recognition of histones with covalent modifications that are associated with gene
activation. An anti-neutrophil IgM recognizing calreticulin, but not
myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus,
alterations in nuclear structure contribute to lupus autoimmunity when expressed
in the context of a lupus-prone genetic background, suggesting a mechanism for
the development of lupus autoimmunity in genetically predisposed individuals that
is induced by the disruption of nuclear architecture.
PMID- 27483356
TI - Small heat shock proteins mediate cell-autonomous and -nonautonomous protection
in a Drosophila model for environmental-stress-induced degeneration.
AB - Cell and tissue degeneration, and the development of degenerative diseases, are
influenced by genetic and environmental factors that affect protein misfolding
and proteotoxicity. To better understand the role of the environment in
degeneration, we developed a genetic model for heat shock (HS)-stress-induced
degeneration in Drosophila This model exhibits a unique combination of features
that enhance genetic analysis of degeneration and protection mechanisms involving
environmental stress. These include cell-type-specific failure of proteostasis
and degeneration in response to global stress, cell-nonautonomous interactions
within a simple and accessible network of susceptible cell types, and precise
temporal control over the induction of degeneration. In wild-type flies, HS
stress causes selective loss of the flight ability and degeneration of three
susceptible cell types comprising the flight motor: muscle, motor neurons and
associated glia. Other motor behaviors persist and, accordingly, the
corresponding cell types controlling leg motor function are resistant to
degeneration. Flight motor degeneration was preceded by a failure of muscle
proteostasis characterized by diffuse ubiquitinated protein aggregates. Moreover,
muscle-specific overexpression of a small heat shock protein (HSP), HSP23,
promoted proteostasis and protected muscle from HS stress. Notably, neurons and
glia were protected as well, indicating that a small HSP can mediate cell
nonautonomous protection. Cell-autonomous protection of muscle was characterized
by a distinct distribution of ubiquitinated proteins, including perinuclear
localization and clearance of protein aggregates associated with the perinuclear
microtubule network. This network was severely disrupted in wild-type
preparations prior to degeneration, suggesting that it serves an important role
in muscle proteostasis and protection. Finally, studies of resistant leg muscles
revealed that they sustain proteostasis and the microtubule cytoskeleton after HS
stress. These findings establish a model for genetic analysis of degeneration and
protection mechanisms involving contributions of environmental factors, and
advance our understanding of the protective functions and therapeutic potential
of small HSPs.
PMID- 27483359
TI - At Least They Know I Give a Damn!
PMID- 27483358
TI - Comparison of the long-term effects of single-dose methotrexate and salpingectomy
on ovarian reserve in terms of anti-mullerian hormone levels.
AB - The aim of this study was to compare the effects of single-dose methotrexate
(MTX) and salpingectomy on ovarian reserve in women with ectopic pregnancy in the
late post-treatment period. A total of 181 patients were included in the study;
56 of them received a single-dose of MTX, 45 of them had undergone salpingectomy
treatment for ectopic pregnancy in the previous 12-18 months, and 80 healthy
women constituted an age-matched control group. The anti-mullerian hormone (AMH),
follicle stimulating hormone (FSH) and oestrogen (E2) levels, as well as antral
follicle counts (AFC) of the patients were evaluated. The average age was similar
in both groups (p = 0.094) and there was no statistically significant difference
in the smoking status of the patients (p = 0.949). None of the three groups
displayed a significant difference in terms of AFC (p = 0.528), AMH (p = 0.147),
FSH (p = 0.393) and E2 levels (p = 0.117). In the treatment of ectopic pregnancy
neither the single-dose MTX application nor the salpingectomy had any permanent
detrimental effect on the ovarian reserve; serum AMH levels and AFC are unaltered
in the long term following single-dose MTX or salpingectomy.
PMID- 27483357
TI - The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma
driven by expression of ALK and MYCN.
AB - The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has
shown remarkable clinical efficacy in treatment of ALK-positive non-small cell
lung cancer. However, in neuroblastoma, activating mutations in the ALK kinase
domain are typically refractory to crizotinib treatment, highlighting the need
for more potent inhibitors. The next-generation ALK inhibitor PF-06463922 is
predicted to exhibit increased affinity for ALK mutants prevalent in
neuroblastoma. We examined PF-06463922 activity in ALK-driven neuroblastoma
models in vitro and in vivo In vitro kinase assays and cell-based experiments
examining ALK mutations of increasing potency show that PF-06463922 is an
effective inhibitor of ALK with greater activity towards ALK neuroblastoma
mutants. In contrast to crizotinib, single agent administration of PF-06463922
caused dramatic tumor inhibition in both subcutaneous and orthotopic xenografts
as well as a mouse model of high-risk neuroblastoma driven by Th-ALK(F1174L)/MYCN
Taken together, our results suggest PF-06463922 is a potent inhibitor of
crizotinib-resistant ALK mutations, and highlights an important new treatment
option for neuroblastoma patients.
PMID- 27483360
TI - Adjunctive Amantadine Treatment for Aggressive Behavior in Children: A Series of
Eight Cases.
AB - PURPOSE: Amantadine has a growing body of evidence for the treatment of
aggressive behavior in patients with traumatic brain injury, autism spectrum
disorder, and developmental disability. We describe our experience with
adjunctive amantadine treatment for aggressive behavior in eight hospitalized
children. METHODS: We conducted a retrospective chart review of psychiatric
inpatients initiated on amantadine for the management of aggressive behavior.
RESULTS: The majority of patients were male (n = 7) ranging in age from 6 to 10
years (mean 8.5). The most common diagnoses were attention-deficit/hyperactivity
disorder (n = 6), intermittent explosive disorder (n = 4), oppositional defiant
disorder (n = 4), and bipolar disorder (n = 3). Five patients had either
borderline intellectual functioning or an unspecified cognitive disorder, and
four patients had either confirmed or suspected in utero substance exposure.
Included patients received amantadine for a minimum of 20 days. Mean adjunctive
amantadine starting dose was 2.6 mg/(kg.day) and mean discharge dose was 6.7
mg/(kg.day). The treating child and adolescent psychiatrist described five
patients as very much improved and three patients as much improved following
amantadine therapy. Average seclusions and PRN medications per week were reduced
from baseline to week 1 of amantadine (1.81, 95% CI [1.02, 2.61] versus 0.25, 95%
CI [0.00, 0.55] (p = 0.01) and 4, 95% CI [2.22, 5.78] versus 1.63, 95% CI [0.71,
2.54] (p = 0.02)), respectively. Both physical restraints and seclusions were
reduced from baseline in the second week of amantadine (1.56, 95% CI [0.45, 2.68]
versus 0.00, 95% CI [0.00, 0.00] [p = 0.04] and 1.81, 95% CI [1.02, 2.61] versus
0.13, 95% CI [0.00, 0.35] [p = 0.01]), respectively. No adverse events related to
amantadine were identified. CONCLUSIONS: We describe clinical improvement
supported by objective measures in eight children with aggressive behavior
treated with adjunctive amantadine. These findings warrant further investigation
as patients were taking other mood stabilizing medications and there are
limitations associated with retrospective chart reviews.
PMID- 27483361
TI - Clinical and genetic characteristics in patients with Huntington's disease from
China.
AB - Huntington's disease (HD) is a neurodegenerative disease caused by the expansion
of unstable CAG repeats in the HTT gene. There are scarce data about HD in China.
Fifty-eight HD patients were consecutively recruited and assessed using the
Unified HD Rating Scale (UHDRS) motor section and UHDRS behaviour assessment
(UHDRS-b). Genetic analyses were also conducted. Thirty-three women and Twenty
five men were diagnosed with a mean age of 46.1 +/- 11.2 years and a mean number
of CAG triplet repeats 44.6 +/- 4.4. CAG triplet repeat number was negatively
correlated with age at onset, and positively correlated with UHDRS-b total score,
and its subdomains including depressed mood, low self-esteem, anxiety and
irritability. On the other hand, negative correlations were identified between
age at onset and UHDRS-b total score, and its subdomains include low self-esteem,
anxiety, suicidal thought, irritability and apathy. Disease durations were
correlated with UHDRS motor scores and anxiety domain of UHDRS-b. This is the
largest series of Chinese HD patients with demographic, clinical and genetic data
confirms the demographic features of Chinese HD patients are comparable to those
in other ethnic backgrounds. CAG triplet repeat number may also predict the
severity of behaviour problems in HD patients besides its predication for age of
onset.
PMID- 27483362
TI - Inclusion of Vancomycin as Part of Broad-Spectrum Coverage Does Not Improve
Outcomes in Patients with Intra-Abdominal Infections: A Post Hoc Analysis.
AB - BACKGROUND: Management of complicated intra-abdominal infections (cIAIs) includes
broad-spectrum antimicrobial coverage and commonly includes vancomycin for the
empiric coverage of methicillin-resistant Staphylococcus aureus (MRSA). Ideally,
culture-guided de-escalation follows to promote robust antimicrobial stewardship.
This study assessed the impact and necessity of vancomycin in cIAI treatment
regimens. PATIENTS AND METHODS: A post hoc analysis of the Study to Optimize
Peritoneal Infection Therapy (STOP-IT) trial was performed. Patients receiving
piperacillin-tazobactam (P/T) and/or a carbapenem were included with
categorization based on use of vancomycin. Univariate and multivariable analyses
evaluated effects of including vancomycin on individual and the composite of
undesirable outcomes (recurrent IAI, surgical site infection [SSI], or death).
RESULTS: The study cohort included 344 patients with 110 (32%) patients receiving
vancomycin. Isolation of MRSA occurred in only eight (2.3%) patients. Vancomycin
use was associated with a similar composite outcome, 29.1%, vs. no vancomycin,
22.2% (p = 0.17). Patients receiving vancomycin had (mean [standard deviation])
higher Acute Physiology and Chronic Health Evaluation II scores (13.1 [6.6] vs.
9.4 [5.7], p < 0.0001), extended length of stay (12.6 [10.2] vs. 8.6 [8.0] d, p <
0.001), and prolonged antibiotic courses (9.1 [8.0] vs. 7.1 [4.9] d, p = 0.02).
After risk adjustment in a multivariate model, no significant difference existed
for the measured outcomes. CONCLUSIONS: This post hoc analysis reveals that
addition of vancomycin occurred in nearly one third of patients and more often in
sicker patients. Despite this selection bias, no appreciable differences in
undesired outcomes were demonstrated, suggesting limited utility for adding
vancomycin to cIAI treatment regimens.
PMID- 27483363
TI - Comparison of the ability of mammalian eEF1A1 and its oncogenic variant eEF1A2 to
interact with actin and calmodulin.
AB - The question as to why a protein exerts oncogenic properties is answered mainly
by well-established ideas that these proteins interfere with cellular signaling
pathways. However, the knowledge about structural and functional peculiarities of
the oncoproteins causing these effects is far from comprehensive. The 97.5%
homologous tissue-specific A1 and A2 isoforms of mammalian translation elongation
factor eEF1A represent an interesting model to study a difference between protein
variants of a family that differ in oncogenic potential. We propose that the
different oncogenic impact of A1 and A2 might be explained by differences in
their ability to communicate with their respective cellular partners. Here we
probed this hypothesis by studying the interaction of eEF1A with two known
partners - calmodulin and actin. Indeed, an inability of the A2 isoform to
interact with calmodulin is shown, while calmodulin is capable of binding A1 and
interferes with its tRNA-binding and actin-bundling activities in vitro. Both A1
and A2 variants revealed actin-bundling activity; however, the form of bundles
formed in the presence of A1 or A2 was distinctly different. Thus, a potential
inability of A2 to be controlled by Ca2+-mediated regulatory systems is revealed.
PMID- 27483364
TI - Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA
expression in advanced serous ovarian cancer.
AB - Most members of the kallikrein-related peptidase family have been demonstrated to
be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion,
and resistance to chemotherapy. In the present study, we assessed the mRNA
expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with
advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation
between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed,
indicating coordinate expression of both peptidases. No significant associations
of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were
found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were
significantly linked with shortened overall survival (OS) (hazard ratio [HR] =
2.07, p = 0.007). While KLK8 values were not associated with patients' outcome,
high KLK6+KLK8 values were significantly associated with shorter progression-free
survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the
case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis,
elevated KLK6 mRNA values, apart from residual tumor mass, remained an
independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA
and protein levels correlate, KLK6 may represent an attractive therapeutic target
for potent and specific inhibitors of its enzymatic activity.
PMID- 27483365
TI - An Evaluation of Mobile Applications for Reproductive Endocrinology and
Infertility Providers.
AB - OBJECTIVE: To identify and rate reproductive endocrinology and infertility (REI)
mobile applications (apps) targeted toward REI providers. DESIGN: A list of REI
apps was found in both the Apple iTunes and Google Play stores using the
following seven MeSH terms: reproductive endocrinology, REI, infertility,
fertility, In Vitro Fertilization, IVF, and embryology. Patient-centered apps
were excluded. The remaining apps were then evaluated for accuracy using reliable
references. SETTING: Mobile technology. PATIENTS/INTERVENTIONS: None. MAIN
OUTCOME MEASURES: Accurate apps were evaluated for comprehensiveness (the extent
of the ability to aid in clinical decision-making) and rated with objective and
subjective components using the APPLICATIONS scoring system. RESULTS: Using the
seven REI-related MeSH terms, 985 apps and 1,194 apps were identified in the
Apple iTunes and Google Play stores, respectively. Of these unique apps, only 20
remained after excluding patient-centered apps. Upon further review for
applicability to REI specifically and content accuracy, only seven apps remained.
These seven apps were then rated using the APPLICATIONS scoring system.
CONCLUSION: Only 0.32% of 2,179 apps reviewed for this study were useful to REI
providers. There is potential for further mobile resource development in the area
of REI, given the limited number and varying comprehensiveness and quality of
available apps.
PMID- 27483366
TI - Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral
Therapy.
AB - BACKGROUND: A major challenge to HIV eradication strategies is the lack of an
accurate measurement of the total burden of replication-competent HIV (the
"reservoir"). We assessed the association of anti-HIV antibody responses and the
estimated size of the reservoir during antiretroviral therapy (ART). METHODS: We
evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems
(LIPS) assay in relation to several blood-based HIV reservoir measures: total and
2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA
(rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR),
and replication-competent virus (outgrowth assay). We also assessed total HIV DNA
and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and
linear regressions were performed using log-transformed blood- or tissue-based
reservoir measurements as predictors and log-transformed antibody levels as
outcome variables. RESULTS: Among 51 chronically HIV-infected ART-suppressed
participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9
years), the most statistically significant associations were between antibody
responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold
increase per two-fold RNA increase, P = 0.004) and between antibody responses to
matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two
fold DNA increase, P = 0.003). However, these associations were not statistically
significant after a stringent Bonferroni-adjustment of P<0.00045. Multivariate
models including age and duration of ART did not markedly alter results.
CONCLUSIONS: Our findings suggest that anti-HIV antibody responses may reflect
the size of the HIV reservoir during chronic treated HIV disease, possibly via
antigen recognition in reservoir sites. Larger, prospective studies are needed to
validate the utility of antibody levels as a measure of the total body burden of
HIV during treatment.
PMID- 27483367
TI - Hand Mycetoma: The Mycetoma Research Centre Experience and Literature Review.
AB - Mycetoma is a devastating, neglected tropical disease characterised by extensive
tissue involvement resulting in destruction, deformities and disabilities in the
affected patients. The hand is commonly affected by mycetoma thus compromises its
functionality and hinder the patient's daily activities of living. In this
communication, we report on 533 patients with hand mycetoma managed over a period
of 24 years at the Mycetoma Research Centre, University of Khartoum, Khartoum,
Sudan. Eumycetoma was the commonest type of mycetoma (83.3%) encountered. Males
were predominately affected (69.2%) with a sex ratio of 2.2:1. The majority of
the patients (84%) were young adult below the age of 40 years old at
presentation. The generality of patients (86.4%) were from the Sudan mycetoma
belt. Children and adolescents (28.1%), farmers (18.2%) and workers (17.4%) were
more frequently affected. The majority of patients (67.4%) had disease duration
of less than 5 years at presentation. The study, did not document significant
history of local trauma, familial tendency, concomitant medical diseases or other
predisposing cause for mycetoma in this population. Pain (23.1%) was not a
disease feature in this series and 52% of patients had past surgery for mycetoma
and recurrence. The right hand was affected most (60.4%), and 64% of them had
small lesion at presentation. Conventional x-ray was only helpful in patients
with advanced disease and the MRI accurately determined the disease extension.
Cytological smears, surgical biopsies histopathological examination and grains
culture were the principal diagnostic tools for causative organisms'
identification. In the present series it was difficult to determine the treatment
outcome due to high patients follow up dropout.
PMID- 27483368
TI - Adverse Renal, Endocrine, Hepatic, and Metabolic Events during Maintenance Mood
Stabilizer Treatment for Bipolar Disorder: A Population-Based Cohort Study.
AB - BACKGROUND: There is limited, poorly characterized information about adverse
events occurring during maintenance treatment of bipolar disorder. We aimed to
determine adverse event rates during treatment with lithium, valproate,
olanzapine, and quetiapine. METHODS AND FINDINGS: We conducted a propensity score
adjusted cohort study using nationally representative United Kingdom electronic
health records from January 1, 1995, until December 31, 2013. We included
patients who had a diagnosis of bipolar disorder and were prescribed lithium (n =
2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as
maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney
disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2
diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity
score included important demographic, physical health, and mental health
predictors of drug treatment allocation. The median duration of drug treatment
was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed
lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of
chronic kidney disease stage 3 or more severe, following adjustment for
propensity score, age, and calendar year, and accounting for clustering by
primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval
[CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001,
quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in
those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR
0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of
new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003,
olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR
0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p =
0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced
relative to lithium. However, rates of greater than 15% weight gain on valproate,
olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p <
0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95%
CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of
hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p =
0.017). We found no significant difference in rates of chronic kidney disease
stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or
hepatotoxicity. Despite estimates being robust following sensitivity analyses,
limitations include the potential for residual confounding and ascertainment bias
and an inability to examine dosage effects. CONCLUSIONS: Lithium use is
associated with more renal and endocrine adverse events but less weight gain than
commonly used alternative mood stabilizers. Risks need to be offset with the
effectiveness and anti-suicidal benefits of lithium and the potential metabolic
side effects of alternative treatment options.
PMID- 27483369
TI - Modelling Transcapillary Transport of Fluid and Proteins in Hemodialysis
Patients.
AB - BACKGROUND: The kinetics of protein transport to and from the vascular
compartment play a major role in the determination of fluid balance and plasma
refilling during hemodialysis (HD) sessions. In this study we propose a whole
body mathematical model describing water and protein shifts across the capillary
membrane during HD and compare its output to clinical data while evaluating the
impact of choosing specific values for selected parameters. METHODS: The model
follows a two-compartment structure (vascular and interstitial space) and is
based on balance equations of protein mass and water volume in each compartment.
The capillary membrane was described according to the three-pore theory. Two
transport parameters, the fractional contribution of large pores (alphaLP) and
the total hydraulic conductivity (LpS) of the capillary membrane, were estimated
from patient data. Changes in the intensity and direction of individual fluid and
solute flows through each part of the transport system were analyzed in relation
to the choice of different values of small pores radius and fractional
conductivity, lymphatic sensitivity to hydraulic pressure, and steady-state
interstitial-to-plasma protein concentration ratio. RESULTS: The estimated values
of LpS and alphaLP were respectively 10.0 +/- 8.4 mL/min/mmHg (mean +/- standard
deviation) and 0.062 +/- 0.041. The model was able to predict with good accuracy
the profiles of plasma volume and serum total protein concentration in most of
the patients (average root-mean-square deviation < 2% of the measured value).
CONCLUSIONS: The applied model provides a mechanistic interpretation of fluid
transport processes induced by ultrafiltration during HD, using a minimum of
tuned parameters and assumptions. The simulated values of individual flows
through each kind of pore and lymphatic absorption rate yielded by the model may
suggest answers to unsolved questions on the relative impact of these not
measurable quantities on total vascular refilling and fluid balance.
PMID- 27483370
TI - Immunologic Function and Molecular Insight of Recombinant Interleukin-18.
AB - In recent years, cytokine-mediated therapy has emerged as further advance
alternative in cancer therapy. Interleukin-18 (IL-18) has exhibited interesting
anti-cancer properties especially when combined with IL-12. We engineered IL-18
in order to improve its activity using single point mutagenesis. IL-18 mutants
were constructed according to binding residues and polarity which we tried to
increase polarity in M33Q and M60Q, enhanced cationicity in E6K, and flexibility
in T63A. All IL-18 proteins were expressed in Pichia pastoris, purified, and then
measured the activity by treating with the NK-92MI cell line to evaluate
interferon-gamma (IFN-gamma) stimulation. The E6K and T63A mutant forms showed
higher activity with respect to native proteins at the concentration of 200 ng mL
1 by inducing the expression of IFN-gamma, about factors of 9 and 4,
respectively. Meanwhile, M33Q and M60Q had no significant activity to induce IFN
gamma. Interestingly, the combination of E6K and T63A mutations could synergize
the induction activity of IL-18 to be 16 times at 200 ng mL-1. Furthermore,
molecular dynamics studies have elucidated the effect due to mutation on
conformation of the binding site of IL-18. The results turn out that E6K provides
structural perseverance against mutation, while M33Q and M60Q promote vivid
overall change in protein conformation, especially at the binding site. For T63A,
mutation yields small difference in structure but clearly increases structural
flexibility. However, a small structural change was observed when T63A was
combined with E6K. Our research resulted in a novel version of IL-18 which could
be a new key candidate for cytokine-mediated therapy.
PMID- 27483371
TI - How Does Awareness Modulate Goal-Directed and Stimulus-Driven Shifts of Attention
Triggered by Value Learning?
AB - In order to behave adaptively, attention can be directed in space either
voluntarily (i.e., endogenously) according to strategic goals, or involuntarily
(i.e., exogenously) through reflexive capture by salient or novel events. The
emotional or motivational value of stimuli can also strongly influence
attentional orienting. However, little is known about how reward-related effects
compete or interact with endogenous and exogenous attention mechanisms,
particularly outside of awareness. Here we developed a visual search paradigm to
study subliminal value-based attentional orienting. We systematically manipulated
goal-directed or stimulus-driven attentional orienting and examined whether an
irrelevant, but previously rewarded stimulus could compete with both types of
spatial attention during search. Critically, reward was learned without conscious
awareness in a preceding phase where one among several visual symbols was
consistently paired with a subliminal monetary reinforcement cue. Our results
demonstrated that symbols previously associated with a monetary reward received
higher attentional priority in the subsequent visual search task, even though
these stimuli and reward were no longer task-relevant, and despite reward being
unconsciously acquired. Thus, motivational processes operating independent of
conscious awareness may provide powerful influences on mechanisms of attentional
selection, which could mitigate both stimulus-driven and goal-directed shifts of
attention.
PMID- 27483372
TI - Kin Recognition in a Clonal Fish, Poecilia formosa.
AB - Relatedness strongly influences social behaviors in a wide variety of species.
For most species, the highest typical degree of relatedness is between full
siblings with 50% shared genes. However, this is poorly understood in species
with unusually high relatedness between individuals: clonal organisms. Although
there has been some investigation into clonal invertebrates and yeast, nothing is
known about kin selection in clonal vertebrates. We show that a clonal fish, the
Amazon molly (Poecilia formosa), can distinguish between different clonal
lineages, associating with genetically identical, sister clones, and use multiple
sensory modalities. Also, they scale their aggressive behaviors according to the
relatedness to other females: they are more aggressive to non-related clones. Our
results demonstrate that even in species with very small genetic differences
between individuals, kin recognition can be adaptive. Their discriminatory
abilities and regulation of costly behaviors provides a powerful example of
natural selection in species with limited genetic diversity.
PMID- 27483373
TI - Variation in Indole-3-Acetic Acid Production by Wild Saccharomyces cerevisiae and
S. paradoxus Strains from Diverse Ecological Sources and Its Effect on Growth.
AB - Phytohormone indole-3-acetic acid (IAA) is the most common naturally occurring
and most thoroughly studied plant growth regulator. Microbial synthesis of IAA
has long been known. Microbial IAA biosynthesis has been proposed as possibly
occurring through multiple pathways, as has been proven in plants. However, the
biosynthetic pathways of IAA and the ecological roles of IAA in yeast have not
been widely studied. In this study, we investigated the variation in IAA
production and its effect on the growth of Saccharomyces cerevisiae and its
closest relative Saccharomyces paradoxus yeasts from diverse ecological sources.
We found that almost all Saccharomyces yeasts produced IAA when cultured in
medium supplemented with the primary precursor of IAA, L-tryptophan (L-Trp).
However, when cultured in medium without L-Trp, IAA production was only detected
in three strains. Furthermore, exogenous added IAA exerted stimulatory and
inhibitory effects on yeast growth. Interestingly, a negative correlation was
observed between the amount of IAA production in the yeast cultures and the IAA
inhibition ratio of their growth.
PMID- 27483374
TI - Myosin Light Chain Kinase (MLCK) Gene Influences Exercise Induced Muscle Damage
during a Competitive Marathon.
AB - Myosin light chain kinase (MLCK) phosphorylates the regulatory light chain (RLC)
of myosin producing increases in force development during skeletal muscle
contraction. It has been suggested that MLCK gene polymorphisms might alter RLC
phosphorylation thereby decreasing the ability to produce force and to resist
strain during voluntary muscle contractions. Thus, the genetic variations in the
MLCK gene might predispose some individuals to higher values of muscle damage
during exercise, especially during endurance competitions. The aim of this
investigation was to determine the influence of MLCK genetic variants on exercise
induced muscle damage produced during a marathon. Sixty-seven experienced runners
competed in a marathon race. The MLCK genotype (C37885A) of these marathoners was
determined. Before and after the race, a sample of venous blood was obtained to
assess changes in serum myoglobin concentrations and leg muscle power changes
were measured during a countermovement jump. Self-reported leg muscle pain and
fatigue were determined by questionnaires. A total of 59 marathoners (88.1%) were
CC homozygotes and 8 marathoners (11.9%) were CA heterozygotes. The two groups of
participants completed the race with a similar time (228 +/- 33 vs 234 +/- 39
min; P = 0.30) and similar self-reported values for fatigue (15 +/- 2 vs 16 +/- 2
A.U.; P = 0.21) and lower-limb muscle pain (6.2 +/- 1.7 vs 6.6 +/- 1.8 cm; P =
0.29). However, CC marathoners presented higher serum myoglobin concentrations
(739 +/- 792 vs 348 +/- 144 MUg.mL-1; P = 0.03) and greater pre-to-post- race leg
muscle power reduction (-32.7 +/- 15.7 vs -21.2 +/- 21.6%; P = 0.05) than CA
marathoners. CA heterozygotes for MLCK C37885A might present higher exercise
induced muscle damage after a marathon competition than CC counterparts.
PMID- 27483375
TI - Gender disparities in mortality from infectious diseases in Serbia, 1991-2014: a
time of civil wars and global crisis.
AB - Infectious diseases remain one of the leading causes of death worldwide. The aim
of this descriptive epidemiological study was to analyse the trends in mortality
from infectious diseases in Serbia (excluding the Autonomous Province of Kosovo &
Metohia) from 1991 to 2014 using joinpoint regression analysis. The mortality
rates from infectious diseases were found to have increased markedly from 1991 to
1994 (+12.4% per year), followed by a significant decline from 1994 to 2009 (
4.6% per year) and then another increase from 2009 to 2014 (+4.3% per year).
Throughout the study period, mortality rates were consistently higher in men than
in women. Although a substantial decline was observed for young people of both
sexes, no consistent pattern was evident for the middle-aged nor the elderly.
Since 1991, septicaemia has emerged as a leading cause of infectious disease
mortality, particularly in older men. The Yugoslav civil wars in the 1990s and
the global financial crisis in 2008 corresponded with changes in the trends in
mortality from infectious diseases in Serbia, with the elderly showing particular
vulnerability during those time periods. Data presented in this study might be
useful to improve control of infectious diseases in Serbia.
PMID- 27483376
TI - Characteristics of child daycare centres associated with clustering of major
enteropathogens.
AB - Insights into transmission dynamics of enteropathogens in children attending
daycare are limited. Here we aimed at identifying daycare centre (DCC)
characteristics associated with time-clustered occurrence of enteropathogens in
DCC-attending children. For this purpose, we used the KIzSS network, which
comprises 43 DCCs that participated in infectious disease surveillance in The
Netherlands during February 2010-February 2013. Space-time scan statistics were
used to identify clusters of rotavirus, norovirus, astrovirus, Giardia lamblia
and Cryptosporidium spp. in a two-dimensional DCC characteristic space
constructed using canonical correlation analysis. Logistic regression models were
then used to further identify DCC characteristics associated with increased or
decreased odds for clustering of enteropathogens. Factors associated with
increased odds for enteropathogen clustering in DCCs were having indoor/outdoor
paddling pools or sandpits, owning animals, high numbers of attending children,
and reporting outbreaks to local health authorities. Factors associated with
decreased odds for enteropathogen clustering in DCCs were cleaning child potties
in designated waste disposal stations, cleaning vomit with chlorine-based
products, daily cleaning of toys, extra cleaning of toys during a suspected
outbreak, and excluding children with gastroenteritis. These factors provide
targets for reducing the burden of gastrointestinal morbidity associated with
time-clustered occurrence of major enteropathogens in DCC attendees.
PMID- 27483377
TI - The authors reply.
PMID- 27483378
TI - Mapping Uncertainty Due to Missing Data in the Global Ocean Health Index.
AB - Indicators are increasingly used to measure environmental systems; however, they
are often criticized for failing to measure and describe uncertainty. Uncertainty
is particularly difficult to evaluate and communicate in the case of composite
indicators which aggregate many indicators of ecosystem condition. One of the
ongoing goals of the Ocean Health Index (OHI) has been to improve our approach to
dealing with missing data, which is a major source of uncertainty. Here we: (1)
quantify the potential influence of gapfilled data on index scores from the 2015
global OHI assessment; (2) develop effective methods of tracking, quantifying,
and communicating this information; and (3) provide general guidance for
implementing gapfilling procedures for existing and emerging indicators,
including regional OHI assessments. For the overall OHI global index score, the
percent contribution of gapfilled data was relatively small (18.5%); however, it
varied substantially among regions and goals. In general, smaller territorial
jurisdictions and the food provision and tourism and recreation goals required
the most gapfilling. We found the best approach for managing gapfilled data was
to mirror the general framework used to organize, calculate, and communicate the
Index data and scores. Quantifying gapfilling provides a measure of the
reliability of the scores for different regions and components of an indicator.
Importantly, this information highlights the importance of the underlying
datasets used to calculate composite indicators and can inform and incentivize
future data collection.
PMID- 27483379
TI - Circumventing the natural, frequent oestrogen waves of the female cheetah
(Acinonyx jubatus) using oral progestin (Altrenogest).
AB - Cheetah are induced ovulators, experiencing short, variable oestrogen waves year
round. Exogenous gonadotrophin administration induces ovulation, but success is
variable and often improves if ovaries are quiescent. After affirming the
presence of short-term oestrogenic waves, we examined the effect of the timing of
administration of exogenous equine and human chorionic gonadotrophins (eCG-hCG)
within the oestrogen concentration pattern on subsequent follicle development and
oocyte and corpus luteum quality. We also investigated ovarian suppression using
an oral progestin (Altrenogest, 7 days) and assessed whether Altrenogest
moderated adrenal activity by reducing glucocorticoid metabolites. All cheetahs
exhibited short (every ~7-10 days), sporadic, year-round increases in faecal
oestradiol punctuated by unpredictable periods (4-10 weeks) of baseline
oestradiol (anoestrous). Gonadotrophin (eCG-hCG) efficacy was not affected by
oestradiol 'wave' pattern if administered >=3 days after an oestrogen peak. Such
cheetahs produced normative faecal progestagen patterns and higher numbers
(P<0.06) of mature oocytes than females given gonadotrophins <=2 days after an
oestradiol peak. Altrenogest supplementation expanded the interval between
oestradiol peaks to 12.9 days compared with 7.3 days without progestin
pretreatment. Altrenogest-fed females excreted less (P<0.05) glucocorticoid
metabolites than non-supplemented counterparts. Results show that Altrenogest is
effective for suppressing follicular activity, may contribute to reduced
glucocorticoid production and may result in more effective ovulation induction
via gonadotrophin therapy.
PMID- 27483380
TI - MicroRNAs as biomarkers for major depression: a role for let-7b and let-7c.
AB - There is a growing emphasis in the field of psychiatry on the need to identify
candidate biomarkers to aid in diagnosis and clinical management of depression,
particularly with respect to predicting response to specific therapeutic
strategies. MicroRNAs are small nucleotide sequences with the ability to regulate
gene expression at the transcriptomic level and emerging evidence from a range of
studies has highlighted their biomarker potential. Here we compared healthy
controls (n=20) with patients diagnosed with major depression (n=40) and who were
treatment-resistant to identify peripheral microRNA biomarkers, which could be
used for diagnosis and to predict response to electroconvulsive therapy (ECT) and
ketamine (KET) infusions, treatments that have previously shown to be effective
in treatment-resistant depression (TRD). At baseline and after treatment, blood
samples were taken and symptom severity scores rated using the Hamilton
Depression Rating Scale (HDRS). Samples were analyzed for microRNA expression
using microarray and validated using quantitative PCR. As expected, both
treatments reduced HDRS scores. Compared with controls, the baseline expression
of the microRNA let-7b was less by ~40% in TRD patients compared with controls.
The baseline expression of let-7c was also lower by ~50% in TRD patients who
received ECT. Bioinformatic analysis revealed that let-7b and let-7c regulates
the expression of 27 genes in the PI3k-Akt-mTOR signaling pathway, which has
previously been reported to be dysfunctional in depression. The expression of miR
16, miR-182, miR-451 and miR-223 were similar to that in controls. Baseline
microRNA expression could not predict treatment response and microRNAs were
unaffected by treatment. Taken together, we have identified let-7b and let-7c as
candidate biomarkers of major depression.
PMID- 27483381
TI - Persistent post-stroke depression in mice following unilateral medial prefrontal
cortical stroke.
AB - Post-stroke depression (PSD) is a common outcome following stroke that is
associated with poor recovery. To develop a preclinical model of PSD, we targeted
a key node of the depression-anxiety circuitry by inducing a unilateral ischemic
lesion to the medial prefrontal cortex (mPFC) stroke. Microinjection of male
C57/BL6 mice with endothelin-1 (ET-1, 1600 pmol) induced a small (1 mm(3)) stroke
consistently localized within the left mPFC. Compared with sham control mice, the
stroke mice displayed a robust behavioral phenotype in four validated tests of
anxiety including the elevated plus maze, light-dark, open-field and novelty
suppressed feeding tests. In addition, the stroke mice displayed depression-like
behaviors in both the forced swim and tail suspension test. In contrast, there
was no effect on locomotor activity or sensorimotor function in the horizontal
ladder, or cylinder and home cage activity tests, indicating a silent stroke due
to the absence of motor abnormalities. When re-tested at 6 weeks post stroke, the
stroke mice retained both anxiety and depression phenotypes. Surprisingly, at 6
weeks post stroke the lesion site was infiltrated by neurons, suggesting that the
ET-1-induced neuronal loss in the mPFC was reversible over time, but was
insufficient to promote behavioral recovery. In summary, unilateral ischemic
lesion of the mPFC results in a pronounced and persistent anxiety and depression
phenotype with no evident sensorimotor deficits. This precise lesion of the
depression circuitry provides a reproducible model to study adaptive cellular
changes and preclinical efficacy of novel interventions to alleviate PSD
symptoms.
PMID- 27483382
TI - Transcriptomic signatures of neuronal differentiation and their association with
risk genes for autism spectrum and related neuropsychiatric disorders.
AB - Genes for autism spectrum disorders (ASDs) are also implicated in fragile X
syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and
converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell
line, the most widely used system to study neurodevelopment, is currently
discussed for its applicability to model cortical development. We implemented an
optimal neuronal differentiation protocol of this system and evaluated
neurodevelopment at the transcriptomic level using the CoNTeXT framework, a
machine-learning algorithm based on human post-mortem brain data estimating
developmental stage and regional identity of transcriptomic signatures. Our
improved model in contrast to currently used SH-SY5Y models does capture early
neurodevelopmental processes with high fidelity. We applied regression modelling,
dynamic time warping analysis, parallel independent component analysis and
weighted gene co-expression network analysis to identify activated gene sets and
networks. Finally, we tested and compared these sets for enrichment of risk genes
for neuropsychiatric disorders. We confirm a significant overlap of genes
implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this
observation, we report that risk genes affect pathways specific for each disorder
during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were
enriched among the positive regulators, but only ID-implicated genes were also
negative regulators of neuronal differentiation. ASD and ID genes were involved
in dendritic branching modules, but only ASD risk genes were implicated in
histone modification or axonal guidance. Only ID genes were over-represented
among cell cycle modules. We conclude that the underlying signatures are disorder
specific and that the shared genetic architecture results in overlaps across
disorders such as ID in ASD. Thus, adding developmental network context to
genetic analyses will aid differentiating the pathophysiology of neuropsychiatric
disorders.
PMID- 27483384
TI - Correction: Direct Measurements of Oxygen Gradients in Spheroid Culture System
Using Electron Parametric Resonance Oximetry.
AB - [This corrects the article DOI: 10.1371/journal.pone.0149492.].
PMID- 27483383
TI - An enzyme in the kynurenine pathway that governs vulnerability to suicidal
behavior by regulating excitotoxicity and neuroinflammation.
AB - Emerging evidence suggests that inflammation has a key role in depression and
suicidal behavior. The kynurenine pathway is involved in neuroinflammation and
regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of
suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite
quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased.
The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits
QUIN formation by competitive production of the neuroprotective metabolite
picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess
QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal
behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients
exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the
Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess
behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide
polymorphisms (SNPs) in 77 of the patients and 150 population-based controls.
Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF
(P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in
CSF were sustained over 2 years after the suicide attempt based on repeated
measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in
suicide attempters and associated with increased CSF QUIN. Taken together, our
data suggest that increased QUIN levels may result from reduced activity of ACMSD
in suicidal subjects. We conclude that measures of kynurenine metabolites can be
explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic
target in suicidal behavior.
PMID- 27483385
TI - A perspective on liquid salts for energy and materials.
AB - Liquid salts comprising molten salts and ionic liquids offer important media to
address both energy and materials challenges. Here we review topics presented in
this Faraday Discussion volume related to improved electrowinning of metals,
optimisation of processes, new electrochemical device concepts, chemistry in
ionic liquids, conversion of biomass, carbon chemistry and nuclear applications.
The underlying phenomenology is then reviewed and commentary given. Some future
applications are then discussed, further exemplifying the high potential rewards
achievable from these chemistries.
PMID- 27483387
TI - Body mass-corrected molecular rate for bird mitochondrial DNA.
AB - Mitochondrial DNA remains one of the most widely used molecular markers to
reconstruct the phylogeny and phylogeography of closely related birds. It has
been proposed that bird mitochondrial genomes evolve at a constant rate of ~0.01
substitution per site per million years, that is that they evolve according to a
strict molecular clock. This molecular clock is often used in studies of bird
mitochondrial phylogeny and molecular dating. However, rates of mitochondrial
genome evolution vary among bird species and correlate with life history traits
such as body mass and generation time. These correlations could cause systematic
biases in molecular dating studies that assume a strict molecular clock. In this
study, we overcome this issue by estimating corrected molecular rates for birds.
Using complete or nearly complete mitochondrial genomes of 475 species, we show
that there are strong relationships between body mass and substitution rates
across birds. We use this information to build models that use bird species' body
mass to estimate their substitution rates across a wide range of common
mitochondrial markers. We demonstrate the use of these corrected molecular rates
on two recently published data sets. In one case, we obtained molecular dates
that are twice as old as the estimates obtained using the strict molecular clock.
We hope that this method to estimate molecular rates will increase the accuracy
of future molecular dating studies in birds.
PMID- 27483388
TI - Arene Selectivity by a Flexible Coordination Polymer Host.
AB - The coordination polymers [Ag4 (O2 CCF3 )4 (phen)3 ]? phen?arene (1?phen?arene)
(phen=phenazine; arene=toluene, p-xylene or benzene) have been synthesised from
the solution phase in a series of arene solvents and crystallographically
characterised. By contrast, analogous syntheses from o-xylene and m-xylene as the
solvent yield the solvent-free coordination polymer [Ag4 (O2 CCF3 )4 (phen)2 ]
(2). Toluene, p-xylene and benzene have been successfully used in mixed-arene
syntheses to template the formation of coordination polymers 1?phen?arene, which
incorporate o- or m-xylene. The selectivity of 1?phen?arene for the arene guests
was determined, through pairwise competition experiments, to be p
xylene>toluene~benzene>o-xylene>m-xylene. The largest selectivity coefficient was
determined as 14.2 for p-xylene:m-xylene and the smallest was 1.0 for
toluene:benzene.
PMID- 27483389
TI - CaMKII inhibition promotes neuronal apoptosis by transcriptionally upregulating
Bim expression.
AB - The effects of Ca/calmodulin-dependent protein kinase II (CaMKII) on neuronal
apoptosis are complex and contradictory, and the underlying mechanisms remain
unclear. Bcl-2-interacting mediator of cell death (Bim) is an important
proapoptotic protein under many physiological and pathophysiological conditions.
However, there is no evidence that CaMKII and Bim are mechanistically linked in
neuronal apoptosis. In this study, we showed that CaMKII inhibition by the
inhibitors KN-62 and myristoylated autocamtide-2-related inhibitory peptide
promoted apoptosis in cerebellar granule neurons in a dose-dependent manner.
CaMKII inhibition increased Bim protein and messenger RNA levels. The expression
of early growth response factor-1, a transcription factor of Bim, was also
induced by CaMKII inhibitors. These data suggested that CaMKII repressed the
transcriptional expression of Bim. Moreover, knockdown of Bim using small
interfering RNAs attenuated the proapoptotic effects of CaMKII inhibition. Taken
together, this is the first report to show that CaMKII inhibition
transcriptionally upregulates Bim expression to promote neuronal apoptosis,
providing new insights into the proapoptotic mechanism of CaMKII inhibition.
PMID- 27483390
TI - Diagnostic dry bone histology in human paleopathology.
AB - Paleopathology is the study of trauma and disease as may be observed in ancient
(human) remains. In contrast to its central role in current medical practice,
microscopy plays a rather modest role in paleopathology. This is at least
partially due to the differences between fresh and decomposed (i.e., skeletonized
or "dry bone") tissue samples. This review discusses these differences and
describes how they affect the histological analysis of paleopathological
specimens. First, we provide a summary of some general challenges related to the
histological analysis of palaeopathological specimens. Second, the reader is
introduced in bone tissue histology and bone tissue dynamics. The remainder of
the paper is dedicated to the diagnostic value of dry bone histology. Its value
and limitations are illustrated by comparing several well-studied
paleopathological cases with similar contemporary, clinical cases. This review
illustrates that due to post-mortem loss of soft tissue, a limited number of
disorders display pathognomonic features during histological analysis of
skeletonized human remains. In the remainder of cases, histology may help to
narrow down the differential diagnosis or is diagnostically unspecific. A
comprehensive, multidisciplinary diagnostic approach therefore remains essential.
Clin. Anat. 29:831-843, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27483391
TI - Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass
balance, elimination route, and metabolite profile in cancer patients.
AB - AIM: This trial (NCT: 01713036) investigated the absolute bioavailability, mass
balance and metabolite profile of pimasertib in a new design combining these
investigations in a single group of patients. METHODS: Six male patients with
pathologically confirmed, locally advanced or metastatic solid tumours were
enrolled. Exclusion criteria included Eastern Cooperative Oncology Group
performance status >1. In Part A of the trial, patients received a 60 mg oral
dose of unlabelled pimasertib followed by an intravenous (i.v.) tracer dose of
[14 C]pimasertib 2 MUg (equalling 9 kBq) as a bolus injection, one hour after the
oral dose, on Day 1. On Day 8, all patients received 60 mg pimasertib capsules
spiked with 2.6 MBq of [14 C]pimasertib. Patients received 60 mg oral unlabelled
pimasertib twice daily from Day 3 to Day 21 of Part A and in subsequent 21-day
cycles in Part B. RESULTS: Following i.v. administration, [14 C]pimasertib
exhibited a geometric mean total body clearance of 45.7 l h-1 (geometric
coefficient of variation [geometric CV]: 47.2%) and a volume of distribution of
229 l (geometric CV: 42.0%). Absolute bioavailability was 73%. The majority of
the oral [14 C] dose (85.1%) was recovered in excreta. Total radioactivity was
mainly excreted into urine (52.8%) and faeces (30.7%) with 78.9% of the [14 C]
dose recovered as metabolites. Two major circulating metabolites were identified
in plasma: a carboxylic acid (M445) and a phosphoethanolamine conjugate (M554).
The safety profile was in line with the published pimasertib trials. CONCLUSION:
Pimasertib showed a favourable pharmacokinetic profile with high absolute
bioavailability and a unique metabolic pathway (conjugation with
phosphoethanolamine).
PMID- 27483392
TI - Power and Confounding in Diffuse Alveolar Hemorrhage Secondary to Antineutrophil
Cytoplasmic Antibody-Associated Vasculitis: Comment on the Article by Cartin-Ceba
et al.
PMID- 27483393
TI - Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal
Transplant Patients: A Validation Study.
AB - Genome-wide association studies (GWAS) are designed to investigate single
nucleotide polymorphisms (SNPs) and the association with a clinical phenotype. A
previous GWAS performed in 300 renal transplant recipients identified two SNPs
(rs3811321 and rs6565887) associated with serum creatinine and clinical outcome.
We sought to validate these findings. Genotyping of the two SNPs was performed
using Taqman assays in 1638 Caucasians participating in the Assessment of LEscol
in Renal Transplant (ALERT) study. Primary endpoint was death-censored graft
loss, and secondary endpoint was all-cause mortality. Applying Cox regression, no
crude association to graft loss was found for rs3811321 on chromosome 14 (hazard
ratio [HR] 0.87, 95% CI 0.59-1.29, p = 0.50) or rs6565887 on chromosome 18 (HR
0.88, CI 0.62-1.25, p = 0.48). Multivariable adjustments did not change results,
nor did evaluation of the number of risk alleles formed by the two SNPs. No
association with mortality was detected. In conclusion, an impact of two SNPs on
chromosomes 14 and 18 on death-censored graft survival or all-cause mortality was
not confirmed. Our results emphasize the importance of validating findings from
high-throughput genetics studies and call for large collaborative research
initiatives in the field of transplantation outcomes.
PMID- 27483395
TI - Directed Assembly of Soft Anisotropic Nanoparticles by Colloid Electrospinning.
AB - Directed assembly of triblock copolymer worms to produce nanostructured fibers is
achieved via colloid electrospinning. These copolymer worms are conveniently
prepared by polymerization-induced self-assembly in concentrated aqueous
dispersion. Addition of a second water-soluble component, poly(vinyl alcohol), is
found to be critical for the production of well-defined fibers: trial experiments
performed using the worms alone produce only spherical microparticles.
Transmission electron microscopy studies confirm that the worm morphology
survives electrospinning and the worms become orientated parallel to the main
axis of the fibers during their generation. The average deviant angle (thetadev )
between the worm orientation and fiber axis decreases from 17 degrees to 9
degrees as the worm/PVA mass ratio increases from 1.15:1 to 5:1, indicating a
greater degree of worm alignment within fibers with higher worm contents and
smaller fiber diameters. Thus triblock copolymer fibers of ~300 +/- 120 nm
diameter can be readily produced that comprise aligned worms on the nanoscale.
PMID- 27483394
TI - Systemic inflammation in decompensated cirrhosis: Characterization and role in
acute-on-chronic liver failure.
AB - Acute-on-chronic liver failure (ACLF) in cirrhosis is characterized by acute
decompensation (AD), organ failure(s), and high short-term mortality. Recently,
we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the
expression of an acute exacerbation of the SI already present in decompensated
cirrhosis. This study was aimed at testing this hypothesis and included 522
patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI
was assessed by measuring 29 cytokines and the redox state of circulating albumin
(HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction
(SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations.
Measurements were performed at enrollment (baseline) in all patients and
sequentially during hospitalization in 255. The main findings of this study were:
(1) Patients with AD without ACLF showed very high baseline levels of
inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed
significantly higher levels of these markers than those without ACLF; (2)
different cytokine profiles were identified according to the type of ACLF
precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial
infection, and others); (3) severity of SI and frequency and severity of ACLF at
enrollment were strongly associated. The course of SI and the course of ACLF
(improvement, no change, or worsening) during hospitalization and short-term
mortality were also strongly associated; and (4) the strength of association of
ACLF with SI was higher than with SCD. CONCLUSION: These data support SI as the
primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249-1264).
PMID- 27483396
TI - Photon Energy Becomes the Third Dimension in Crystallographic Texture Analysis.
AB - Conventional analysis of the preferred orientation of crystallites
(crystallographic texture) involves X-ray diffraction with area detectors and 2D
data output. True 3D, spatially resolved information requires sample rotation in
the beam, thus changing the probed volume, which introduces signal smearing and
precludes the scanning of complex structures. This obstacle has been overcome by
energy-dispersive Laue diffraction. A method has been devised to reach a large
portion of reciprocal space and translate the X-ray photon energy into the
missing third dimension of space. Carbon fibers and lobster exoskeleton as
examples of biomineralized tissue have been analyzed. The major potential of this
method lies in its "one-shot" nature and the direct 3D information requiring no
previous knowledge of the sample. It allows the texture of large samples with
complex substructures to be scanned and opens up the conceptual possibility of
following texture changes in situ, for example, during crystallization.
PMID- 27483397
TI - Gated Channels and Selectivity Tuning of CO2 over N2 Sorption by Post-Synthetic
Modification of a UiO-66-Type Metal-Organic Framework.
AB - The highly porous and stable metal-organic framework (MOF) UiO-66 was altered
using post-synthetic modifications (PSMs). Prefunctionalization allowed the
introduction of carbon double bonds into the framework through a four-step
synthesis from 2-bromo-1,4-benzenedicarboxylic acid; the organic linker 2-allyl
1,4-benzenedicarboxylic acid was obtained. The corresponding functionalized MOF
(UiO-66-allyl) served as a platform for further PSMs. From UiO-66-allyl, epoxy,
dibromide, thioether, diamine, and amino alcohol functionalities were
synthesized. The abilities of these compounds to adsorb CO2 and N2 were compared,
which revealed the structure-selectivity correlations. All synthesized MOFs
showed profound thermal stability together with an increased ability for
selective CO2 uptake and molecular gate functionalities at low temperatures.
PMID- 27483399
TI - In-vitro antileishmanial potential of peptide drug hirudin.
AB - Hirudin is clinically an important drug used for the treatment of cardiac
diseases, but has never been elucidated for antileishmanial potential. This study
was designed to determine the therapeutic utility of hirudin against
leishmaniasis. Binding affinities of 28 potent proteinase inhibitors were
screened computationally against leishmanolysin (GP63), out of which hirudin
exhibited higher binding affinity with GP63 and good expected IC50 values.
Experimentally, hirudin showed most promising activity against promastigote and
axenic amastigote forms of leishmanial parasites with IC50 values of 0.60 +/-
0.36 MUg/mL and 0.43 +/- 0.23 MUg/mL, respectively, in a dose- and time-dependent
assay. The cytotoxicity assay revealed no adverse effects on human macrophages
with LD50 value of 860.11 +/- 53.44 MUg/mL. Hirudin caused leishmanial cell death
mainly by apoptosis and membrane permeability. In spite of the basic knowledge
obtained, hirudin mechanism is considerably less prone to the induction of
resistance than classical drugs. Collectively, this study fosters further studies
for the hirudin as new antileishmania lead with a new mode of action.
PMID- 27483398
TI - Cell wall biochemical alterations during Agrobacterium-mediated expression of
haemagglutinin-based influenza virus-like vaccine particles in tobacco.
AB - Influenza virus-like particles (VLPs) have been shown to induce a safe and potent
immune response through both humoral and cellular responses. They represent
promising novel influenza vaccines. Plant-based biotechnology allows for the
large-scale production of VLPs of biopharmaceutical interest using different
model organisms, including Nicotiana benthamiana plants. Through this platform,
influenza VLPs bud from the plasma membrane and accumulate between the membrane
and the plant cell wall. To design and optimize efficient production processes, a
better understanding of the plant cell wall composition of infiltrated tobacco
leaves is a major interest for the plant biotechnology industry. In this study,
we have investigated the alteration of the biochemical composition of the cell
walls of N. benthamiana leaves subjected to abiotic and biotic stresses induced
by the Agrobacterium-mediated transient transformation and the resulting high
expression levels of influenza VLPs. Results show that abiotic stress due to
vacuum infiltration without Agrobacterium did not induce any detectable
modification of the leaf cell wall when compared to non infiltrated leaves. In
contrast, various chemical changes of the leaf cell wall were observed post
Agrobacterium infiltration. Indeed, Agrobacterium infection induced deposition of
callose and lignin, modified the pectin methylesterification and increased both
arabinosylation of RG-I side chains and the expression of arabinogalactan
proteins. Moreover, these modifications were slightly greater in plants
expressing haemagglutinin-based VLP than in plants infiltrated with the
Agrobacterium strain containing only the p19 suppressor of silencing.
PMID- 27483400
TI - [Not Available].
AB - In this case report we illustrate how incorrectly prepared and cooked seeds from
white lupin - a common snack among people from parts of the Mediterranean and
Middle East - caused an anticholinergic syndrome in a previously healthy man. The
symptoms subsided without treatment and the patient was discharged from the
hospital in good health. Anticholinergic syndrome results from inhibition of the
parasympatic nervous system. The symptoms commonly include dry mouth, confusion,
hallucinations, fever, tachycardia, and urine retention. The syndrome may most
frequently be provoked by overdose of drugs such as prometazin, hyoscyamin, and
biperidin or by ingestion of plants such as belladonna, datura and henbane. The
aim of this report is to increase clinicians' awareness of white lupin's
anticholinergic effects.
PMID- 27483402
TI - [Not Available].
PMID- 27483401
TI - [Not Available].
AB - Biochemical changes after strenuous exercise - data from the Kalmar Ironman
Strenuous and prolonged exercise like marathon, ultra running and triathlon can
lead to changes in biomarkers of cardiac, muscle and kidney functional damage. We
present the data of 30 (15 men, 15 women) participants of the Kalmar Ironman
2015. Pre-race electrocardiograms and echocardiograms showed a high frequency of
abnormalities. Post race elevations of troponin T, creatine kinase, myoglobin, N
terminal prohormone of brain natriuretic peptide, and creatinine returned to
normal in almost all cases within 5-8 days. In all but one participant the
troponin T pattern was compatible with the diagnosis of myocardial infarction. It
is an up-to-date unanswered question whether the increase of troponin represents
myocardial damage or just is a benign consequence of an intermittent change of
the permeability of myocardial cell membranes.
PMID- 27483403
TI - [Not Available].
PMID- 27483405
TI - [Not Available].
PMID- 27483404
TI - [Not Available].
PMID- 27483406
TI - [Not Available].
PMID- 27483408
TI - [Not Available].
PMID- 27483407
TI - [Not Available].
PMID- 27483409
TI - Irrigating grazed pasture decreases soil carbon and nitrogen stocks.
AB - The sustainability of using irrigation to produce food depends not only on the
availability of sufficient water, but also on the soil's 'response' to
irrigation. Stocks of carbon (C) and nitrogen (N) are key components of soil
organic matter (SOM), which is important for sustainable agricultural production.
While there is some information about the effects of irrigation on soil C stocks
in cropping systems, there is a paucity of such studies in pastoral food
production systems. For this study, we sampled soils from 34 paired, irrigated
and unirrigated pasture sites across New Zealand (NZ) and analysed these for
total C and N. On average, irrigated pastures had significantly (P < 0.05) less
soil carbon (C) and nitrogen (N) than adjacent unirrigated pastures, with
differences of 6.99 t C ha-1 and 0.58 t N ha-1 in the uppermost 0.3 m.
Differences in C and N tended to occur throughout the soil profile, so the
cumulative differences increased with depth, and the proportion of the soil C
lost from deeper horizons was large. There were no relationships between
differences in soil C and N stocks and the length of time under irrigation. This
study suggests SOM will decrease when pastures under a temperate climate are
irrigated. On this basis, increasing the area of temperate pasture land under
irrigation would result in more CO2 in the atmosphere and may directly and
indirectly increase N leaching to groundwater. Given the large and increasing
area of land being irrigated both in NZ and on a global scale, there is an urgent
need to determine whether the results found in this study are also applicable in
other regions and under different land management systems (e.g. arable).
PMID- 27483410
TI - Improvement of High-Density Lipoprotein Function in Patients With Early
Rheumatoid Arthritis Treated With Methotrexate Monotherapy or Combination
Therapies in a Randomized Controlled Trial.
AB - OBJECTIVE: Abnormal function of high-density lipoprotein (HDL) has been
implicated as a potential mechanism for the increased incidence of cardiovascular
(CV) disease in patients with rheumatoid arthritis (RA). This study was
undertaken to evaluate changes in HDL function and HDL-associated proteins over 2
years of follow-up in patients with early RA receiving either methotrexate (MTX)
monotherapy, MTX + etanercept (ETN) combination therapy, or MTX + sulfasalazine
(SSZ) + hydroxychloroquine (HCQ) triple therapy in the Treatment of Early
Aggressive Rheumatoid Arthritis (TEAR) trial. METHODS: The antioxidant capacity
of HDL, paraoxonase 1 (PON-1) activity, and levels of HDL-associated haptoglobin
(Hp), HDL-associated apolipoprotein A-I (Apo A-I), and myeloperoxidase (MPO) were
measured in 550 TEAR participants at 4 time points (time 0 [pretreatment] and at
24, 48, and 102 weeks of treatment). Repeated-measures analysis using mixed
effects linear models with an autoregressive covariate structure was performed to
model the within-subject covariance over time. RESULTS: Mixed-effects models,
which were controlled for traditional CV risk factors, treatment regimen,
prednisone use, and statin use, demonstrated significant associations between RA
disease activity, measured using the Disease Activity Score in 28 joints,
erythrocyte sedimentation rate, or C-reactive protein level, and the profile of
HDL function over time. Specifically, decreases in RA disease activity over time
were associated with increases in PON-1 activity and levels of HDL-associated Apo
A-I, and decreases in the HDL inflammatory index and levels of MPO and HDL
associated Hp. CONCLUSION: Reduced disease activity in patients with early RA
treated with MTX monotherapy, MTX + ETN combination therapy, or MTX + SSZ + HCQ
triple therapy in the TEAR trial was associated with improvements in the HDL
function profile. Additional studies are warranted to evaluate abnormal HDL
function as a potential mechanism and therapeutic target for CV risk in patients
with RA.
PMID- 27483411
TI - Is the Site of Back Pain Related to the Location of Magnetic Resonance Imaging
Lesions in Patients With Chronic Back Pain? Results From the Spondyloarthritis
Caught Early Cohort.
AB - OBJECTIVE: To determine associations between magnetic resonance imaging (MRI)
lesions originating from either axial spondyloarthritis (SpA) or from
degeneration and pain in patients with chronic back pain of <2 years duration.
METHODS: Patients from the Spondyloarthritis Caught Early (SPACE) cohort
identified the sites of pain (thoracic, lumbar, buttock). The average MRI scores
from 2 readers for axial SpA lesions and from 2 different readers for
degenerative lesions were used. Associations between sacroiliac (SI) joint
lesions and buttock pain were investigated by logistic regression analysis, and
associations between axial SpA or degenerative lesions and pain in the spine
(thoracic and lumbar) were investigated using generalized estimating equations.
Interactions with sex, age, HLA-B27, and fulfillment of Assessment of
SpondyloArthritis international Society (ASAS) criteria were tested. RESULTS: In
348 patients (126 males, 127 fulfilling ASAS criteria, mean age 29.4 years),
spinal MRI (and SI joint images in 342) were available. Pain was localized in the
thoracic spine (35.9%), the lumbar spine (82.5%), or in the buttock(s) (57.8%).
Inflammatory lesions of the SI joint (odds ratio [OR] 1.06; P = 0.04) and
erosions of the SI joint in patients <25 years (OR 1.16; P = 0.04) were
associated with buttock pain. Axial SpA spinal lesions were not associated with
pain. Modic type 1 lesions in patients >35 years (OR 5.19; P = 0.001), high
intensity zone lesions in females not fulfilling ASAS criteria (OR 5.09; P =
0.001), and herniation in various subgroups (OR range 2.07-4.66) were associated
with pain. CONCLUSION: Specific degenerative lesions, but not typical axial SpA
lesions, of the spine are associated with pain at the same location in some
subgroups. Inflammatory lesions in the SI joint are associated with buttock pain.
PMID- 27483412
TI - Association between Mediterranean diet and head and neck cancer: results of a
large case-control study in Italy.
AB - The Mediterranean diet (MD) is a known protective factor for head and neck cancer
(HNC); however, there is still a lack of studies investigating this association
by HNC subsite. The aim of the present study was therefore to evaluate the
association between adherence to MD and HNC overall and by cancer subsite, as
well as the effect of the individual food components on HNC risk. A case-control
study was carried out at the Gemelli Hospital of Rome (Italy). A total of 500 HNC
cases and 433 controls were interviewed. Dietary intake was assessed through a
validated food frequency questionnaire that collected information on over 25 food
items. Odds ratios (ORs) and 95% confidence intervals (CI) of HNC were calculated
using a multiple logistic regression model. We found a reduced risk of both oral
cavity and pharynx cancer (OR=0.61; CI: 0.54-0.70) and larynx cancer (OR=0.64;
CI: 0.56-0.73) with increasing adherence to MD. We also found a high consumption
of fruit, vegetables, and legumes to be significantly associated with a lower
risk of larynx as well as oral cavity and pharynx cancers. Our study showed that
adherence to MD acts protectively against HNC overall and by cancer subsite.
PMID- 27483413
TI - Prostate cancer incidence and mortality in Portugal: trends, projections and
regional differences.
AB - There is a large geographical variability in prostate cancer incidence and
mortality trends, mostly because of heterogeneity in control efforts across
regions. We aimed to describe the time trends in prostate cancer incidence and
mortality in Portugal, overall and by region, and to estimate the number of
incident cases and deaths in 2020. The number of cases and incidence rates in
1998-2009 were collected from the Regional Cancer Registries. The number of
deaths and mortality rates were obtained from the WHO mortality database (1988
2003 and 2007-2013) and Statistics Portugal (2004-2006; 1991-2013 by region).
JoinPoint analyses were used to identify significant changes in trends in age
standardized incidence and mortality rates. Incidence and mortality predictions
for 2020 were performed using Poisson regression models and population
projections provided by Statistics Portugal. In Portugal, prostate cancer
incidence has been increasing since 1998 (1.8%/year), with the exception of the
North Region, with a decrease since 2006 (-3.2%/year). An overall mortality
decline has been observed since 1997 (-2.2%/year), although there were two
patterns of mortality variation at the regional level: one with an inflection
point or significant variation in the rates and the other without significant
variation. If these trends are maintained, ~8600 incident cases and 1700 deaths
may be expected to occur in Portugal in 2020. Despite the overall increasing
incidence and decreasing mortality, there is a large heterogeneity across
regions. Future studies should address regional differences in the trends of
prostate specific antigen screening and in the effective management of prostate
cancer.
PMID- 27483414
TI - The Addition of Epinephrine to Proxymetacaine or Oxybuprocaine Solution Increases
the Depth and Duration of Cutaneous Analgesia in Rats.
AB - BACKGROUND: The aim of this experiment was to investigate the interaction between
epinephrine and 2 local anesthetics (proxymetacaine or oxybuprocaine) using
subcutaneous injections under the hairy skin, thereby simulating infiltration
blocks. METHODS: Using a rat model of cutaneous trunci muscle reflex in response
to local skin pinpricks, the anesthetic properties of proxymetacaine and
oxybuprocaine alone and in combination with epinephrine as an infiltrative
anesthetic were tested. Isobolographic analysis was used for the analgesic
interactions between adjuvant epinephrine and the local anesthetics. Lidocaine
was used as a control group. RESULTS: Oxybuprocaine, proxymetacaine, and
lidocaine elicited a dose-dependent block to pinpricks. On the 50% effective dose
(ED50) basis, their relative potencies were proxymetacaine [0.126 (0.113-0.141)
MUmol] greater than oxybuprocaine [0.208 (0.192-0.226) MUmol] greater than
lidocaine [6.331 (5.662-7.079) MUmol] (P < 0.01 for each comparison). On an
equipotent basis (ED25, ED50, and ED75), sensory block duration elicited by
oxybuprocaine or proxymetacaine was greater than that elicited by lidocaine (P <
0.01). Coadministration of proxymetacaine, oxybuprocaine, or lidocaine with
epinephrine produced a synergistic analgesic effect and prolonged the cutaneous
analgesic effect. After adding epinephrine, oxybuprocaine was much faster,
reaching its maximal blockade, than proxymetacaine or lidocaine (P < 0.01).
CONCLUSIONS: We concluded that proxymetacaine and oxybuprocaine were more potent
and produced greater duration of nociceptive block than lidocaine. The use of
epinephrine augmented the potency and prolonged the duration of proxymetacaine,
oxybuprocaine, and lidocaine as an infiltrative anesthetic.
PMID- 27483415
TI - Relative Contribution of Adjuvants to Local Anesthetic for Prolonging the
Duration of Peripheral Nerve Blocks in Rats.
AB - BACKGROUND AND OBJECTIVES: A chemically compatible, safe 4-drug multimodal
formulation of bupivacaine combined with 3 adjuvants (clonidine, buprenorphine,
and dexamethasone) has been proposed for long-lasting single-injection peripheral
nerve blocks in patients. However, the relative importance of each of the
adjuvants of the 4-drug formulation in producing long-lasting nerve blocks has
not been determined. The aim of this study in rats was to determine which
adjuvants (clonidine, buprenorphine, or dexamethasone) are essential for
producing a long-lasting nerve block. METHODS: After baseline sensory and motor
responses were recorded, 0.1 mL of drug solution was injected into the sciatic
notch of rats. Animals were reevaluated at 10-minute intervals after injection
for the absence or presence of sensory and motor response in the sciatic nerve.
The 4-drug formulation of 0.25% bupivacaine plus all 3 adjuvants (clonidine,
buprenorphine, and dexamethasone), 0.25% bupivacaine with 1 or 2 of the adjuvants
added separately, and 0.25% bupivacaine alone were compared for duration of nerve
block. RESULTS: The 4-drug multimodal solution produced a longer duration of
sensory and motor nerve block than 0.25% bupivacaine alone (P < 0.0001).
Bupivacaine plus clonidine also produced a longer duration of nerve block than
0.25% bupivacaine alone (P = 0.0157), but bupivacaine plus buprenorphine or
bupivacaine plus dexamethasone did not prolong nerve block compared to
bupivacaine alone. There was no difference (P = 0.1414) in the duration of nerve
block between the 4-drug multimodal solution versus bupivacaine plus clonidine.
CONCLUSIONS: This animal study confirmed that the 4-drug multimodal formulation
proposed for clinical nerve block produces superior duration of action compared
to local anesthetic alone. This rat sciatic nerve model also indicated that one
of the 3 adjuvants, clonidine, could by itself account for the extended duration
of nerve block of bupivacaine.
PMID- 27483416
TI - Drug Resistance Characteristics and Macrolide-Resistant Mechanisms of
Streptococcus pneumoniae in Wenzhou City, China.
AB - BACKGROUND Streptococcus pneumoniae (SP) is a Gram-positive, alpha-hemolytic,
facultative anaerobic member of the genus Streptococcus. The erythromycin
resistant methylase (erm) gene and macrolide efflux (mef) gene are the 2 main
genes that can mediate SP. Transposon (Tn) also plays an important role in the
collection and metastasis of the gene. In the present study we investigated the
drug resistance characteristics and the macrolide-resistant mechanisms of SP in
Wenzhou City, China. MATERIAL AND METHODS Sixty-eight strains of SP were isolated
from sputum samples of hospitalized children in the Second Affiliated Hospital of
Wenzhou Medical University. These strains were analyzed using antimicrobial
susceptibility tests to determine their drug resistance to 10 kinds of
antibacterials. Macrolide-resistant phenotypes were identified using K-B method.
PCR method was used to analyze the erm B gene, mef A gene, and int Tn gene.
RESULTS Drug resistance rates of 68 strains of SP were 98.5%, 100.0%, 63.2%,
52.9%, 94.1%, 89.7%, 0.0%, 0.0%, 16.2%, and 14.7% for clindamycin, erythromycin,
penicillin G, cefotaxime, tetracycline, sulfamethoxazole/trimethoprim,
levofloxacin, vancomycin, chloramphenicol, and amoxicillin, respectively. Total
detection rates of the erm B gene, mef A gene, and int Tn gene were 98.5%, 91.2%,
and 100.0%, respectively. CONCLUSIONS SP shows significant multi-drug resistance
in Wenzhou City, whereas there is no clinical value of macrolides antibiotics for
SP. cMLSB mediated by erm B gene is the most predominant phenotype among
macrolide-resistant SP. The int Tn gene may play an important role in horizontal
transfer and clonal dissemination of SP drug resistance genes in Wenzhou City.
PMID- 27483417
TI - Combined Approach to Phacoemulsification and Trabeculectomy Results in Less Ideal
Refractive Outcomes Compared With the Sequential Approach.
AB - PURPOSE: To compare the refractive outcomes of combined versus sequential
trabeculectomy and then phacoemulsification. METHODS: We compared eyes that
underwent uncomplicated combined phacotrabeculectomy (combined group, 87 eyes),
phacoemulsification at least 3 months after trabeculectomy (sequential group, 56
eyes), and phacoemulsification only (control group, 78 eyes) between January 1,
2006 and January 1, 2014. The main outcome measure was refractive prediction
error (RPE)-defined as postoperative subjective spherical equivalent refraction
minus predicted spherical equivalent refraction. RESULTS: The study population
was predominantly Chinese and the mean age at their cataract surgery was 67.2+/
9.59 years. Compared with controls, RPE (-0.40+/-0.70 vs. -0.01+/-0.50, P<0.001)
and mean absolute error (0.62+/-0.50 vs. 0.39+/-0.31, P=0.003) were greater for
the combined group but not for the sequential group. Proportionately fewer
patients in the combined group achieved final subjective refraction within +/
0.5D (27.6% vs. 46.2%, P=0.01) compared with controls. Within the sequential
group, there were no differences in RPE when the fellow eye axial length was used
to predict refractive outcome (P=0.17) or between the group with precataract
surgery IOPs of <=11 mm Hg (-0.28+/-0.82) and the group with >11 mm Hg (-0.28+/
0.53, P=0.99). For the sequential group, the use of contact A scan yielded less
RPE compared with IOLMaster (P=0.01). CONCLUSIONS: Combined approach to
trabeculectomy and phacoemulsification resulted in greater myopic RPEs that were
expectedly greater than those found in the phacoemulsification group.
PMID- 27483418
TI - Structure-Functional Parameters in Differentiating Between Patients With
Different Degrees of Glaucoma.
AB - PURPOSE: We evaluated spectral-domain optical coherence tomography (SD-OCT)
parameters and visual field parameters in patients with different degrees of open
angle glaucoma (preperimetric, mild, moderate, and severe glaucoma) to determine
which parameter best identifies each glaucomatous group. MATERIALS AND METHODS: A
total of 131 patients (66 preperimetric, 41 mild, 35 moderate, 40 severe
glaucomatous eyes) and 40 normal eyes (control group) were included in this
prospective study. The SD-OCT parameters [mean ganglion cell complex (GCC),
superior GCC, inferior GCC, global loss volume, focal loss volume, mean
circumpapillary retinal nerve fiber layer (RNFL), superior circumpapillary
retinal nerve fiber layer [cpRNFL], and inferior cpRNFL] and visual field
parameters (mean deviation and pattern SD) were evaluated. The area under the
receiver operating characteristic curve (AUROC) was calculated for each parameter
to determine which best identified glaucomatous changes. RESULTS: Of the SD-OCT
parameters, inferior (AUROC, 0.792) and mean GCC thickness (AUROC, 0.741) best
discriminated between normal eyes and preperimetric glaucoma eyes. CONCLUSIONS:
GCC measurements were more efficient than cpRNFL measurements in detecting
preperimetric glaucomatous damage. This finding could be an aid to an early
diagnosis.
PMID- 27483419
TI - Bleb Revision With Temporalis Fascia Autograft.
AB - PURPOSE: We report the first description of temporalis fascia autograft to repair
a late leakage bleb with scleral defect that occurred long time after
trabeculectomy with mitomycin C. PATIENT: A 65-year-old woman was referred to our
hospital with chronic late bleb leakage on her right eye. She had previously
undergone a trabeculectomy with mitomycin C 3 years ago for a pigmentary
glaucoma. Bleb leakage occurred 11/2 year after the initial surgery. She
underwent 2 surgical revisions consisting of a conjunctival advancement then an
autologous conjunctival with partial scleral grafts without success. The initial
best-corrected visual acuity of the right eye was 20/50 (Snellen scale). Slit
lamp examination revealed an avascular filtering bleb with leakage (massive
positive Seidel test) and a scleral defect. The anterior chamber was deep and
intraocular pressure (IOP) was 9 mm Hg.Faced with the risk of blebitis,
endophthalmitis, and with the failure of the previous surgeries announced
earlier, a surgical revision with autologous superficial temporalis fascia graft
was decided to repair the leaking bleb. After local anesthesia, a sample of
superficial temporalis fascia was harvested. The necrotic avascular conjunctiva
around the bleb was dissected to separate and excise it from the sclera. The
autologous fascia graft was sutured on the scleral defect with 10-0 nylon.
Subsequently healthy conjunctiva was sutured above the graft. RESULTS: No bleb
leakage occurred postoperatively, best-corrected visual acuity improved to 20/25,
and IOP remained within normal levels 6 months after surgery without IOP-lowering
medication. CONCLUSIONS: Superficial temporalis fascia autograft seems to be an
effective, safe, and easy technique for ophthalmologists. It is a new procedure
in the management of late-onset bleb leakage.
PMID- 27483420
TI - Long-term Outcomes of a Modified Technique Using the Baerveldt Glaucoma Implant
for the Treatment of Refractory Glaucoma.
AB - PURPOSE OF THE STUDY: The purpose of the study was to evaluate the long-term
effectiveness and safety profile of Baerveldt glaucoma implant (BGI) in patients
with refractory glaucoma operated using a modified technique to avoid
postoperative complications. PATIENTS AND METHODS: A total of 160 eyes from 147
glaucomatous patients were enrolled in a consecutive interventional
noncomparative case series. All the patients were treated with a 350-mm BGI using
a modified technique. Intraocular pressure (IOP), the number of medications, the
complications, and the postoperative interventions were reported preoperatively
and during the follow-up. Postoperative IOP and the rate of complications were
the primary outcome measures. The complete and qualified surgical success was the
second endpoint. RESULTS: BGI obtained a mean IOP reduction from 31.8+/-6.4 mm Hg
(baseline) to 14.4+/-3.5 mm Hg after a mean follow-up period of 38.4+/-9.6
months. The mean number of medications reduced between preoperative (n=3.17+/
1.03) and postoperative period (n=0.58+/-0.83) (P<0.0001). Cumulative probability
of maintaining an IOP between 5 and 21 mm Hg and/or a 25% or greater reduction in
IOP was 78.7% at 1 year and 72.1% at 4 years, including 39 eyes (24.4%) in which
postoperative interventions were required (qualified success). If we exclude
those eyes from the analysis, the probability of complete success was 93.4% at 1
year and 91.4% at 4 years in 75.4% of the eyes. CONCLUSIONS: This modified
technique achieved a high percentage of surgical success during the whole follow
up time and was effective in preventing the most serious immediate complications
of nonvalved tube shunts.
PMID- 27483421
TI - Association of the BDNF Val66Met polymorphism with BMI in chronic schizophrenic
patients and healthy controls.
AB - Several lines of evidence suggest that a functional variant of the brain-derived
neurotrophic factor gene (BDNF Val66Met) correlates with a number of eating
disorders. Studies have also shown that the BDNF Val66Met polymorphism was
associated with weight gain in patients with schizophrenia on long-term
antipsychotic treatment. This study aimed to determine whether there was a
relationship between the BDNF Val66Met polymorphism and BMI values in patients
with chronic schizophrenia. We compared 308 Han Chinese patients with
schizophrenia on long-term antipsychotic medication with 304 healthy normal
controls on BDNF polymorphism. Body weight and BMI were measured before breakfast
on the day blood samples were taken. The symptomatology of schizophrenia was
assessed using the Positive and Negative Syndrome Scale. The results showed that
the BDNF Val66Met polymorphism was associated with the BMI value, with genotype
having a strong effect on the mean BMI value in male but not in female patients.
Our results suggest that variation in the BDNF gene may be a risk factor for
weight gain in male patients with schizophrenia on long-term antipsychotic
treatment.
PMID- 27483426
TI - Natural Mineral-Based Solid Oxide Fuel Cell with Heterogeneous Nanocomposite
Derived from Hematite and Rare-Earth Minerals.
AB - Solid oxide fuel cells (SOFCs) have attracted much attention worldwide because of
their potential for providing clean and reliable electric power. However, their
commercialization is subject to the high operating temperatures and costs. To
make SOFCs more competitive, here we report a novel and attractive nanocomposite
hematite-LaCePrOx (hematite-LCP) synthesized from low-cost natural hematite and
LaCePr-carbonate mineral as an electrolyte candidate. This heterogeneous
composite exhibits a conductivity as high as 0.116 S cm(-1) at 600 degrees C
with an activation energy of 0.50 eV at 400-600 degrees C. For the first time, a
fuel cell using such a natural mineral-based composite demonstrates a maximum
power density of 625 mW cm(-2) at 600 degrees C and notable power output of 386
mW cm(-2) at 450 degrees C. The extraordinary ionic conductivity and device
performances are primarily attributed to the heterophasic interfacial conduction
effect of the hematite-LCP composite. These superior properties, along with the
merits of ultralow cost, abundant storage, and eco-friendliness, make the new
composite a highly promising material for commercial SOFCs.
PMID- 27483428
TI - Measurements of nanoresonator-qubit interactions in a hybrid quantum
electromechanical system.
AB - Experiments to probe the basic quantum properties of motional degrees of freedom
of mechanical systems have developed rapidly over the last decade. One promising
approach is to use hybrid electromechanical systems incorporating superconducting
qubits and microwave circuitry. However, a critical challenge facing the
development of these systems is to achieve strong coupling between mechanics and
qubits while simultaneously reducing coupling of both the qubit and mechanical
mode to the environment. Here we report measurements of a qubit-coupled
mechanical resonator system consisting of an ultra-high-frequency nanoresonator
and a long coherence-time superconducting transmon qubit, embedded in a
superconducting coplanar waveguide cavity. It is demonstrated that the
nanoresonator and transmon have commensurate energies and transmon coherence
times are one order of magnitude larger than for all previously reported qubit
coupled nanoresonators. Moreover, we show that numerical simulations of this new
hybrid quantum system are in good agreement with spectroscopic measurements and
suggest that the nanoresonator in our device resides at low thermal occupation
number, near its ground state, acting as a dissipative bath seen by the qubit. We
also outline how this system could soon be developed as a platform for
implementing more advanced experiments with direct relevance to quantum
information processing and quantum thermodynamics, including the study of
nanoresonator quantum noise properties, reservoir engineering, and nanomechanical
quantum state generation and detection.
PMID- 27483429
TI - Odor Identification Test in Idiopathic REM-Behavior Disorder and Parkinson's
Disease in China.
AB - BACKGROUND: Olfactory dysfunction is common in Parkinson's disease (PD) and
idiopathic rapid eye movement sleep behavior disorder (iRBD), which is a risk
factor in the development of PD. However, a few studies have conflicting results
when comparing dysosmia in the patients with iRBD and PD. There is no study
investigating the olfactory function in Chinese patients with iRBD. Additionally,
the Sniffin' Sticks screening 12 test (SS-12) contains several odors that are not
familiar to people in different cultures. METHODS: Odor identification was
evaluated in iRBD patients (n = 54), PD patients (n = 54) and healthy controls (n
= 54). With the identification data, a brief odor identification test was
established and then validated in other subjects. RESULTS: Odor identification
scores in iRBD patients were significantly higher than those in PD patients
(P<0.001) but lower than those in controls (P<0.001). At the cut-off value of
7.5, the Sniffin' Sticks clearly differentiated iRBD and PD patients from the
controls, and the brief test could increase the specificity in diagnosing PD.
Neither the Sniffin' Sticks nor the brief test could clearly differentiate PD and
iRBD patients from each other. CONCLUSIONS: Olfaction is more impaired in PD
patients than in iRBD patients, possibly due to the heterogeneity of iRBD
patients. The Sniffin' Sticks could be a useful tool for differentiating iRBD
patients from the healthy population, and it could be useful for screening people
at high-risk of PD in China, especially when combined with polysomnography. To
reduce the expense and time required for the Sniffin' Sticks test, this study
shows that a brief test is feasible.
PMID- 27483430
TI - Multidrug-Resistant Tuberculosis Treatment in North Korea: Is Scale-Up Possible?
AB - Kwonjune Seung and colleagues describe the Eugene Bell Foundation's experience of
treating MDR-TB in North Korea.
PMID- 27483431
TI - Post-exposure Treatment with Anti-rabies VHH and Vaccine Significantly Improves
Protection of Mice from Lethal Rabies Infection.
AB - Post-exposure prophylaxis (PEP) against rabies infection consists of a
combination of passive immunisation with plasma-derived human or equine immune
globulins and active immunisation with vaccine delivered shortly after exposure.
Since anti-rabies immune globulins are expensive and scarce, there is a need for
cheaper alternatives that can be produced more consistently. Previously, we
generated potent virus-neutralising VHH, also called Nanobodies, against the
rabies glycoprotein that are effectively preventing lethal disease in an in vivo
mouse model. The VHH domain is the smallest antigen-binding functional fragment
of camelid heavy chain-only antibodies that can be manufactured in microbial
expression systems. In the current study we evaluated the efficacy of half-life
extended anti-rabies VHH in combination with vaccine for PEP in an intranasal
rabies infection model in mice. The PEP combination therapy of systemic anti
rabies VHH and intramuscular vaccine significantly delayed the onset of disease
compared to treatment with anti-rabies VHH alone, prolonged median survival time
(35 versus 14 days) and decreased mortality (60% versus 19% survival rate), when
treated 24 hours after rabies virus challenge. Vaccine alone was unable to rescue
mice from lethal disease. As reported also for immune globulins, some
interference of anti-rabies VHH with the antigenicity of the vaccine was
observed, but this did not impede the synergistic effect. Post exposure treatment
with vaccine and human anti-rabies immune globulins was unable to protect mice
from lethal challenge. Anti-rabies VHH and vaccine act synergistically to protect
mice after rabies virus exposure, which further validates the possible use of
anti-rabies VHH for rabies PEP.
PMID- 27483432
TI - The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers.
AB - Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays
a key role in the progression and development of human cancers. Although the
prognostic and clinicopathological features of SIRT3 expression in various
cancers have been investigated by different research groups, however,
inconsistent and opposing results can be observed. In this study, we therefore
performed a meta-analysis to evaluate the significance of SIRT3 expression in
various cancers. Systematic literature searching was performed in PubMed, Embase,
China National Knowledge Infrastructure, and Wanfang Data up to November 2015.
Total effect analyses and subgroup analyses were performed to evaluate the
relationship between SIRT3 expression and overall survival, cancer/non-cancer
tissues, lymph node metastasis, pathological differentiation, tumor node
metastasis (TNM) stage, tumor size, and gender, in various cancer patients.
Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were
calculated to clarify the risk or hazard association. A total of 14 studies
comprising 2165 cancer patients were included to assess the association between
SIRT3 immunohistochemical expression and overall survival or clinicopathological
characteristics. SIRT3 expression was significantly associated with overall
survival in gastric cancer (HR = 0.62, 95% CI = 0.43-0.89, P = 0.009) and
hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42-0.74, P<0.0001),
cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI
= 0.01-0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR =
2.20, 95% CI = 1.49-3.26, P<0.0001), and also pathological differentiation in
hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48-0.98, P = 0.04) and
gastric cancer patients (OR = 0.33, 95% CI = 0.21-0.50, P<0.00001), by subgroup
analyses. Furthermore, SIRT3 expression was significantly associated with
pathological differentiation in total effect analysis (OR = 0.46, 95% CI = 0.29
0.74, P = 0.001). No detectable relation between SIRT3 expression and other
clinicopathological parameters were found. This meta-analysis indicates that
SIRT3 expression level is associated with prognostic and clinical features in
specific cancers.
PMID- 27483433
TI - Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian
Cancer-Associated Peritonitis.
AB - The most common properties of oncogenes are cell proliferation and the prevention
of apoptosis in malignant cells, which, as a consequence, induce tumor formation
and dissemination. However, the effects of oncogenes on the tumor
microenvironment (TME) have not yet been examined in detail. The accumulation of
ascites accompanied by chronic inflammation and elevated concentrations of VEGF
is a hallmark of the progression of ovarian cancer. We herein demonstrated the
mechanisms by which oncogenes contribute to modulating the ovarian cancer
microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer
cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the
peritoneal cavities of C57/BL6 mice and the production of ascites was assessed.
ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in
vivo, whereas no significant differences were observed in proliferative activity
in vitro. ID8-KRAS in particular induced the production of ascites, which
accumulated between approximately two to three weeks after the injection, more
rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and
seven weeks, respectively). VEGF concentrations in ascites significantly
increased in c-MYC-induced ovarian cancer, whereas the concentrations of
inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian
cancer and were accompanied by an increased number of neutrophils in ascites. A
cytokine array revealed that KRAS markedly induced the expression of granulocyte
macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest
that oncogenes promote cancer progression by modulating the TME in favor of
cancer progression.
PMID- 27483434
TI - Luminescent platforms for monitoring changes in the solubility of amylin and
huntingtin in living cells.
AB - Luminescent, cell-based assays capable of monitoring the aggregation potential of
the disease-relevant proteins known as amylin (type 2 diabetes) and huntingtin
(Huntington's disease) are presented. These sensitive platforms report on the
influence of mutations as well as small molecules on protein solubility.
PMID- 27483435
TI - Protein Kinase RNA-Like Endoplasmic Reticulum Kinase-Mediated Bcl-2 Protein
Phosphorylation Contributes to Evodiamine-Induced Apoptosis of Human Renal Cell
Carcinoma Cells.
AB - We investigated the anticancer mechanism of evodiamine (EVO) against the
viability of human A498 renal cell carcinoma (RCC) cells in vitro and in vivo.
The in vitro study showed that EVO decreased the viability of A498 cells with the
occurrence of apoptotic characteristics such as hypodiploid cells, DNA ladders,
chromatin-condensed cells, and cleaved caspase (Casp)-3/poly(ADP ribose)
polymerase (PARP) proteins. Pharmacological studies using chemical inhibitors of
mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)
indicated that phosphorylation of the c-Jun N-terminal kinase (JNK) protein
participated in EVO-induced cell death of A498 cells, and application of the JNK
inhibitor, SP600125 (SP), inhibited EVO-induced cleavage of the Casp-3/PARP
proteins and chromatin condensation according to Giemsa staining. EVO disruption
of the mitochondrial membrane potential (MMP) with increased protein levels of
the phosphorylated Bcl-2 protein (p-Bcl-2) was prevented by JNK inhibitors in
A498 cells. A structure-activity relationship study showed that a methyl group at
position 14 in EVO was important for its apoptotic effects and increased p-Bcl-2
protein in A498 cells. Furthermore, significant increases in the phosphorylated
endoplasmic reticular stress protein, protein kinase RNA-like endoplasmic
reticulum kinase (p-PERK at Thr980), by EVO were detected in A498 cells, and the
PERK inhibitor, GSK2606414, significantly suppressed EVO-induced apoptosis, p
JNK, p-PERK, and cleaved PARP proteins. The in vivo study showed that EVO
significantly reduced RCC growth elicited by a subcutaneous injection of A498
cells, and an increased protein level of p-PERK was observed according to an
immunohistochemical analysis. Apoptosis by EVO was also demonstrated in other RCC
cells such as 786-O, ACHN, and Caki-1 cells. This is the first study to
demonstrate the anti-RCC effect of EVO via apoptosis in vitro and in vivo, and
activation of JNK and PERK to induce Bcl-2 protein phosphorylation, which led to
disruption of the MMP.
PMID- 27483437
TI - Flow Cytometric Immunophenotyping Is Sensitive for the Early Diagnosis of De Novo
Aggressive Natural Killer Cell Leukemia (ANKL): A Multicenter Retrospective
Analysis.
AB - Aggressive natural killer cell leukemia (ANKL) is a fatal hematological neoplasm
characterized by a fulminating clinical course and extremely high mortality.
Current diagnosis of this disease is not effective during the early stages and it
is easily misdiagnosed as other NK cell disorders. We retrospectively analyzed
the clinical characteristics and flow cytometric immunophenotype of 47 patients
with ANKL. Patients with extranodal NK/T cell lymphoma, nasal type (ENKTL) and
chronic lymphoproliferative disorder of NK cell (CLPD-NK), who were diagnosed
during the same time period were used for comparisons. Abnormal NK cells in ANKL
were found to have a distinctiveCD56bright/CD16dim immunophenotype and markedly
increased Ki-67 expression, whereas CD57 negativity and reduced expression of
killer immunoglobulin-like receptor (KIR), CD161, CD7, CD8 and perforin were
exhibited compared with other NK cell proliferative disorders (p<0.05). The
positive rates of flow cytometry detection (97.4%) was higher than those of
cytomorphological (89.5%), immunohistochemical (90%), cytogenetic (56.5%) and F
18 fluorodeoxyglucose positron emission tomography/computer tomography (18-FDG
PET/CT) examinations (50%) (p<0.05). ANKL is a highly aggressive leukemia with
high mortality. Flow cytometry detection is sensitive for the early and
differential diagnosis of ANKL with high specificity.
PMID- 27483438
TI - Oxidized Lipoprotein as a Major Vessel Cell Proliferator in Oxidized Human Serum.
AB - Oxidative stress is correlated with the incidence of several diseases such as
atherosclerosis and cancer, and oxidized biomolecules have been determined as
biomarkers of oxidative stress; however, the detailed molecular relationship
between generated oxidation products and the promotion of diseases has not been
fully elucidated. In the present study, to clarify the role of serum oxidation
products in vessel cell proliferation, which is related to the incidence of
atherosclerosis and cancer, the major vessel cell proliferator in oxidized human
serum was investigated. Oxidized human serum was prepared by free radical
exposure, separated using gel chromatography, and then each fraction was added to
several kinds of vessel cells including endothelial cells and smooth muscle
cells. It was found that a high molecular weight fraction in oxidized human serum
specifically induced vessel cell proliferation. Oxidized lipids were contained in
this high molecular weight fraction, while cell proliferation activity was not
observed in oxidized lipoprotein-deficient serum. Oxidized low-density
lipoproteins induced vessel cell proliferation in a concentration-dependent
manner. Taken together, these results indicate that oxidized lipoproteins
containing lipid oxidation products function as a major vessel cell proliferator
in oxidized human serum. These findings strongly indicate the relevance of
determination of oxidized lipoproteins and lipid oxidation products in the
diagnosis of vessel cell proliferation-related diseases such as atherosclerosis
and cancer.
PMID- 27483439
TI - Benefits of Intraaortic Balloon Support for Myocardial Infarction Patients in
Severe Cardiogenic Shock Undergoing Coronary Revascularization.
AB - BACKGROUND: Prior studies have suggested intraaortic balloon pump (IABP) have a
neutral effect on acute myocardial infarction (AMI) patients with cardiogenic
shock (CS). However, the effects of IABP on patients with severe CS remain
unclear. We therefore investigated the benefits of IABP in AMI patients with
severe CS undergoing coronary revascularization. METHODS AND RESULTS: This study
identified 14,088 adult patients with AMI and severe CS undergoing coronary
revascularization from Taiwan's National Health Insurance Research Database
between January 1, 1997 and December 31, 2011, dividing them into the IABP group
(n = 7044) and the Nonusers group (n = 7044) after propensity score matching to
equalize confounding variables. The primary outcomes included myocardial
infarction(MI), cerebrovascular accidents or cardiovascular death. In-hospital
events including dialysis, stroke, pneumonia and sepsis were secondary outcomes.
Primary outcomes were worse in the IABP group than in the Nonusers group in 1
month (Hazard ratio (HR) = 1.97, 95% confidence interval (CI) = 1.84-2.12). The
MI rate was higher in the IABP group (HR = 1.44, 95% CI = 1.16-1.79), and the
cardiovascular death was much higher in the IABP group (HR = 2.07, 95% CI = 1.92
2.23). The IABP users had lower incidence of dialysis (8.5% and 9.5%, P = 0.04),
stroke (2.6% and 3.8%, P<0.001), pneumonia (13.9% and 16.5%, P<0.001) and sepsis
(13.2% and 16%, P<0.001) during hospitalization than Nonusers. CONCLUSION: The
use of IABP in patients with myocardial infarction and severe cardiogenic shock
undergoing coronary revascularization did not improve the outcomes of recurrent
myocardial infarction and cardiovascular death. However, it did reduce the
incidence of dialysis, stroke, pneumonia and sepsis during hospitalization.
PMID- 27483440
TI - Epigenetic contribution to successful polyploidizations: variation in global
cytosine methylation along an extensive ploidy series in Dianthus broteri
(Caryophyllaceae).
AB - Polyploidization is a significant evolutionary force in plants which involves
major genomic and genetic changes, frequently regulated by epigenetic factors. We
explored whether natural polyploidization in Dianthus broteri complex resulted in
substantial changes in global DNA cytosine methylation associated to ploidy.
Global cytosine methylation was estimated by high-performance liquid
chromatography (HPLC) in 12 monocytotypic populations with different ploidies
(2*, 4*, 6*, 12*) broadly distributed within D. broteri distribution range. The
effects of ploidy level and local variation on methylation were assessed by
generalized linear mixed models (GLMMs). Dianthus broteri exhibited a higher
methylation percent (~33%) than expected by its monoploid genome size and a large
variation among study populations (range: 29.3-35.3%). Global methylation tended
to increase with ploidy but did not significantly differ across levels due to
increased variation within the highest-order polyploidy categories. Methylation
varied more among hexaploid and dodecaploid populations, despite such cytotypes
showing more restricted geographic location and increased genetic relatedness
than diploids and tetraploids. In this study, we demonstrate the usefulness of an
HPLC method in providing precise and genome reference-free global measure of DNA
cytosine methylation, suitable to advance current knowledge of the roles of this
epigenetic mechanism in polyploidization processes.
PMID- 27483441
TI - High Fat Diet Inhibits Dendritic Cell and T Cell Response to Allergens but Does
Not Impair Inhalational Respiratory Tolerance.
AB - The incidence of obesity has risen to epidemic proportions in recent decades,
most commonly attributed to an increasingly sedentary lifestyle, and a 'western'
diet high in fat and low in fibre. Although non-allergic asthma is a well
established co-morbidity of obesity, the influence of obesity on allergic asthma
is still under debate. Allergic asthma is thought to result from impaired
tolerance to airborne antigens, so-called respiratory tolerance. We sought to
investigate whether a diet high in fats affects the development of respiratory
tolerance. Mice fed a high fat diet (HFD) for 8 weeks showed weight gain,
metabolic disease, and alteration in gut microbiota, metabolites and glucose
metabolism compared to age-matched mice fed normal chow diet (ND). Respiratory
tolerance was induced by repeated intranasal (i.n.) administration of ovalbumin
(OVA), prior to induction of allergic airway inflammation (AAI) by sensitization
with OVA in alum i.p. and subsequent i.n. OVA challenge. Surprisingly,
respiratory tolerance was induced equally well in HFD and ND mice, as evidenced
by decreased lung eosinophilia and serum OVA-specific IgE production. However, in
a pilot study, HFD mice showed a tendency for impaired activation of airway
dendritic cells and regulatory T cells compared with ND mice after induction of
respiratory tolerance. Moreover, the capacity of lymph node cells to produce IL-5
and IL-13 after AAI was drastically diminished in HFD mice compared to ND mice.
These results indicate that HFD does not affect the inflammatory or B cell
response to an allergen, but inhibits priming of Th2 cells and possibly dendritic
cell and regulatory T cell activation.
PMID- 27483442
TI - Transcriptome modulation during host shift is driven by secondary metabolites in
desert Drosophila.
AB - High-throughput transcriptome studies are breaking new ground to investigate the
responses that organisms deploy in alternative environments. Nevertheless, much
remains to be understood about the genetic basis of host plant adaptation. Here,
we investigate genome-wide expression in the fly Drosophila buzzatii raised in
different conditions. This species uses decaying tissues of cactus of the genus
Opuntia as primary rearing substrate and secondarily, the necrotic tissues of the
columnar cactus Trichocereus terscheckii. The latter constitutes a harmful host,
rich in mescaline and other related phenylethylamine alkaloids. We assessed the
transcriptomic responses of larvae reared in Opuntia sulphurea and T.
terscheckii, with and without the addition of alkaloids extracted from the
latter. Whole-genome expression profiles were massively modulated by the rearing
environment, mainly by the presence of T. terscheckii alkaloids. Differentially
expressed genes were mainly related to detoxification, oxidation-reduction and
stress response; however, we also found genes involved in development and
neurobiological processes. In conclusion, our study contributes new data onto the
role of transcriptional plasticity in response to alternative rearing
environments.
PMID- 27483443
TI - Outcomes and satisfaction of two optional cadaveric dissection courses: A 3-year
prospective study.
AB - Teaching time dedicated to anatomy education has been reduced at many medical
schools around the world, including Nova Medical School in Lisbon, Portugal. In
order to minimize the effects of this reduction, the authors introduced two
optional, semester-long cadaveric dissection courses for the first two years of
the medical school curriculum. These courses were named Regional Anatomy I (RAI)
and Regional Anatomy II (RAII). In RAI, students focus on dissecting the thorax,
abdomen, pelvis, and perineum. In RAII, the focus shifts to the head, neck, back,
and upper and lower limbs. This study prospectively analyzes students' academic
achievement and perceptions within the context of these two, newly-introduced,
cadaveric dissection courses. Students' satisfaction was assessed anonymously
through a questionnaire that included items regarding students' perception of the
usefulness of the courses for undergraduate teaching, as well as with regards to
future professional activity. For each of the three academic years studied, the
final score (1 to 20) in General Anatomy (GA), RAI, and RAII was on average 14.26
+/- 1.89; 16.94 +/- 1.02; 17.49 +/- 1.01, respectively. The mean results were
lower in GA than RAI or RAII (P < 0.001). Furthermore, students who undertook
these courses ranked them highly with regards to consolidating their knowledge of
anatomy, preparing for other undergraduate courses, and training for future
clinical practice. These survey data, combined with data on participating
students' academic achievement, lend strong support to the adoption of similar
courses as complementary and compulsory disciplines in a modern medical
curriculum. Anat Sci Educ 10: 127-136. (c) 2016 American Association of
Anatomists.
PMID- 27483444
TI - Vapor-Phase Deposition and Modification of Metal-Organic Frameworks: State-of-the
Art and Future Directions.
AB - Materials processing, and thin-film deposition in particular, is decisive in the
implementation of functional materials in industry and real-world applications.
Vapor processing of materials plays a central role in manufacturing, especially
in electronics. Metal-organic frameworks (MOFs) are a class of nanoporous
crystalline materials on the brink of breakthrough in many application areas.
Vapor deposition of MOF thin films will facilitate their implementation in micro-
and nanofabrication research and industries. In addition, vapor-solid
modification can be used for postsynthetic tailoring of MOF properties. In this
context, we review the recent progress in vapor processing of MOFs, summarize the
underpinning chemistry and principles, and highlight promising directions for
future research.
PMID- 27483445
TI - Ethics Reporting in Biospecimen and Genetic Research: Current Practice and
Suggestions for Changes.
AB - Modern approaches for research with human biospecimens employ a variety of
substantially different types of ethics approval and informed consent. In most
cases, standard ethics reporting such as "consent and approval was obtained" is
no longer meaningful. A structured analysis of 120 biospecimen studies recently
published in top journals revealed that more than 85% reported on consent and
approval, but in more than 90% of cases, this reporting was insufficient and thus
potentially misleading. Editorial policies, reporting guidelines, and material
transfer agreements should include recommendations for meaningful ethics
reporting in biospecimen research. Meaningful ethics reporting is possible
without higher word counts and could support public trust as well as networked
research.
PMID- 27483446
TI - Analysis of Multiple HPV E6 PDZ Interactions Defines Type-Specific PDZ
Fingerprints That Predict Oncogenic Potential.
AB - The high-risk Human Papillomavirus (HPV) E6 oncoproteins are characterised by the
presence of a class I PDZ-binding motif (PBM) on their extreme carboxy termini.
The PBM is present on the E6 proteins derived from all cancer-causing HPV types,
but can also be found on some related non-cancer-causing E6 proteins. We have
therefore been interested in investigating the potential functional differences
between these different E6 PBMs. Using an unbiased proteomic approach in
keratinocytes, we have directly compared the interaction profiles of these
different PBMs. This has allowed us to identify the potential PDZ target
fingerprints of the E6 PBMs from 7 different cancer-causing HPV types, from 3 HPV
types with weak cancer association, and from one benign HPV type that possesses
an ancestral PBM. We demonstrate a striking increase in the number of potential
PDZ targets bound by each E6 PBM as cancer-causing potential increases, and show
that the HPV-16 and HPV-18 PBMs have the most flexibility in their PDZ target
selection. Furthermore, the specific interaction with hScrib correlates directly
with increased oncogenic potential. In contrast, hDlg is bound equally well by
all the HPV E6 PBMs analysed, indicating that this is an evolutionarily conserved
interaction, and was most likely one of the original E6 PBM target proteins that
was important for the occupation of a potential new niche. Finally, we present
evidence that the cell junction components ZO-2 and beta-2 syntrophin are novel
PDZ domain-containing targets of a subset of high-risk HPV types.
PMID- 27483448
TI - Solitary fibrous tumour presenting as a submucosal colonic polyp: a new addition
to the family of mesenchymal polyps of the gastrointestinal tract.
PMID- 27483447
TI - Validation of a Chiral Liquid Chromatographic Method for the Degradation Behavior
of Flumequine Enantiomers in Mariculture Pond Water.
AB - In this work, flumequine (FLU) enantiomers were separated using a Chiralpak OD-H
column, with n-hexane-ethanol (20:80, v/v) as the mobile phase at a flow rate of
0.6 mL/min. Solid phase extraction (SPE) was used for cleanup and enrichment. The
limit of detection, limit of quantitation, linearity, precision, and
intra/interday variation of the chiral high-performance liquid chromatography
(HPLC) method were determined. The developed method was then applied to
investigate the degradation behavior of FLU enantiomers in mariculture pond water
samples. The results showed that the degradation of FLU enantiomers under
natural, sterile, or dark conditions was not enantioselective. Chirality 28:649
655, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27483449
TI - Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine
Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis:
Implications for Disease Pathogenesis.
AB - OBJECTIVE: Antibodies to the citrullinated protein antigens (ACPAs) are important
in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the
prevalence of ACPAs with different fine specificities in different populations is
unclear. This study sought to examine the fine specificity of the antibody
responses toward citrullinated proteins in RA patients from Malaysia, an area
where genetic and environmental determinants of RA are different from those in
more frequently studied cohorts of Caucasian subjects. METHODS: A multiplex
analytic microarray system was used to analyze the occurrence of antibodies to 10
different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17,
Vim60-75], fibrinogen [Fibalpha563-583, Fibalpha580-600, Fibbeta36-52, Fibbeta62
81a, Fibbeta62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in
serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827
healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction
threshold for each peptide was set separately for each population based on a
specificity of 98%. RESULTS: Distinct differences in the frequencies of 5 ACPA
fine specificities (Vim60-75, Vim2-17, Fibbeta62-81b, Eno5-21, and CitCII355-378)
were found between the Malaysian and Swedish RA populations, despite a nearly
identical percentage of patients in each population who were positive for anti
cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with
Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%,
corrected P [Pcorr ] = 1.06 * 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr =
0.02) were significantly higher, while the frequencies of antibodies to Vim2-17
(25% versus 32%, Pcorr = 1.91 * 10-4 ), Fibbeta62-81b (15% versus 30%, Pcorr =
2.47 * 10-22 ), and Eno5-21 (23% versus 50%, Pcorr = 3.64 * 10-57 ) were
significantly lower. CONCLUSION: Serum ACPA fine specificities differ between RA
patients in different populations, although the total proportions of individuals
positive for ACPAs are similar. Differing patterns of ACPA fine specificity could
be attributed to variations in genetic and/or environmental factors.
PMID- 27483450
TI - Effect of Conidiobolus coronatus on the Cuticular and Internal Lipid Composition
of Tettigonia viridissima Males.
AB - Conidiobolus coronatus is an entomopathogenic fungus which has a potential as a
biological control agent of insects. The cuticular and internal lipid composition
of infected and noninfected Tettigonia viridissima males were analyzed by GC/MS.
A total of 49 compounds were identified in the infected and noninfected males,
including fatty acids, fatty acid methyl esters (FAMEs), n-alkanes, alcohols,
sterols, and other organic compounds. The most abundant components of the
cuticular and internal lipids of the insects were fatty acids. After exposure to
C. coronatus, the cuticular lipids of the T. viridissima males contained 17 free
fatty acids from C(8) to C(22), while the cuticular lipids of the noninfected
insects contained only 15 fatty acids from C(12) to C(24). The cuticular and
internal lipids of both the infected and the noninfected males also contained
five FAMEs from C(15) to C(19), seven n-alkanes from C(25) to C(34), five
alcohols from C(16) to C(25), five sterols, and the following six other organic
compounds: azelaic acid, phenylacetic acid, glutaric acid, benzoic acid, sebacic
acid, and glycerol. The compounds which were present only in the cuticular lipids
of the infected males could be due to fungal infection.
PMID- 27483451
TI - Prospective study of guideline-tailored therapy with direct-acting antivirals for
hepatitis C virus-associated mixed cryoglobulinemia.
AB - : Hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) vasculitis
commonly regresses upon virus eradication, but conventional therapy with
pegylated interferon and ribavirin yields approximately 40% sustained virologic
responses (SVR). We prospectively evaluated the efficacy and safety of sofosbuvir
based direct-acting antiviral therapy, individually tailored according to the
latest guidelines, in a cohort of 44 consecutive patients with HCV-associated MC.
In two patients MC had evolved into an indolent lymphoma with monoclonal B-cell
lymphocytosis. All patients had negative HCV viremia at week 12 (SVR12) and at
week 24 (SVR24) posttreatment, at which time all had a clinical response of
vasculitis. The mean (+/-standard deviation) Birmingham Vasculitis Activity Score
decreased from 5.41 (+/-3.53) at baseline to 2.35 (+/-2.25) (P < 0.001) at week 4
on treatment to 1.39 (+/-1.48) (P < 0.001) at SVR12 and to 1.27 (+/-1.68) (P <
0.001) at SVR24. The mean cryocrit value fell from 7.2 (+/-15.4)% at baseline to
2.9 (+/-7.4)% (P < 0.01) at SVR12 and to 1.8 (+/-5.1)% (P < 0.001) at SVR24.
Intriguingly, in the 2 patients with MC and lymphoma there was a partial clinical
response of vasculitis and ~50% decrease of cryocrit, although none experienced a
significant decrease of monoclonal B-cell lymphocytosis. Adverse events occurred
in 59% of patients and were generally mild, with the exception of 1 patient with
ribavirin-related anemia requiring blood transfusion. CONCLUSION: Interferon
free, guideline-tailored therapy with direct-acting antivirals is highly
effective and safe for HCV-associated MC patients; the overall 100% rate of
clinical response of vasculitis, on an intention-to-treat basis, opens the
perspective for curing the large majority of these so far difficult-to-treat
patients. (Hepatology 2016;64:1473-1482).
PMID- 27483452
TI - A Novel and Non-Cytotoxic Self-Healing Supramolecular Elastomer Synthesized with
Small Molecular Biological Acids.
AB - A novel and non-cytotoxic self-healing supramolecular elastomer (SE) is
synthesized with small-molecular biological acids by hydrogen-bonding
interactions. The synthesized SEs behave as rubber at room temperature without
additional plasticizers or crosslinkers, which is attributed to the phase
separated structure. The SE material exhibits outstanding self-healing capability
at room temperature and essential non-cytotoxicity, which makes it a potential
candidate for biomedical applications.
PMID- 27483453
TI - A Precise Chemical Strategy To Alter the Receptor Specificity of the Adeno
Associated Virus.
AB - The ability to target the adeno-associated virus (AAV) to specific types of
cells, by altering the cell-surface receptor it binds, is desirable to generate
safe and efficient therapeutic vectors. Chemical attachment of receptor-targeting
agents onto the AAV capsid holds potential to alter its tropism, but is limited
by the lack of site specificity of available conjugation strategies. The
development of an AAV production platform is reported that enables incorporation
of unnatural amino acids (UAAs) into specific sites on the virus capsid.
Incorporation of an azido-UAA enabled site-specific attachment of a cyclic-RGD
peptide onto the capsid, retargeting the virus to the alphav beta3 integrin
receptors, which are overexpressed in tumor vasculature. Retargeting ability was
site-dependent, underscoring the importance of achieving site-selective capsid
modification. This work provides a general chemical approach to introduce various
receptor binding agents onto the AAV capsid with site selectivity to generate
optimized vectors with engineered infectivity.
PMID- 27483454
TI - Synthesis of an Open-Cage Structure POSS Containing Various Functional Groups and
Their Effect on the Formation and Properties of Langmuir Monolayers.
AB - Recently, silsesquioxanes have been recognized as a new group of film-forming
materials. This study has been aimed at determining the effect of the kind of
functional groups present in two different open-cage structure POSS molecules on
the possibility of the formation of Langmuir monolayers and their properties. To
achieve this goal, two new POSS derivatives (of open-cage structures) containing
polyether and fluoroalkyl functional groups have been synthesized on the basis of
a hydrosilylation process. An optimization of the process was performed, which
makes it possible to obtain the above-mentioned derivatives with high yields. In
the next step, the Langmuir technique was applied to measurements of the surface
pressure (pi) - the mean molecular area (A) isotherms during the compression of
monolayers formed by molecules of the two POSS derivatives considered.
Subsequently, the monolayers were transferred onto quartz plates according to the
Langmuir-Blodgett technique. Both derivatives are able to form insoluble Langmuir
films at the air-water interface, which can be transferred onto a solid substrate
and effectively change its wetting properties.
PMID- 27483455
TI - On Children, Blood, and Cancer: A new section of PBC.
PMID- 27483456
TI - Real-time PCR detection of Didemnum perlucidum (Monniot, 1983) and Didemnum
vexillum (Kott, 2002) in an applied routine marine biosecurity context.
AB - Prevention and early detection are well recognized as the best strategies for
minimizing the risks posed by nonindigenous species (NIS) that have the potential
to become marine pests. Central to this is the ability to rapidly and accurately
identify the presence of NIS, often from complex environmental samples like
biofouling and ballast water. Molecular tools have been increasingly applied to
assist with the identification of NIS and can prove particularly useful for
taxonomically difficult groups like ascidians. In this study, we have developed
real-time PCR assays suited to the specific identification of the ascidians
Didemnum perlucidum and Didemnum vexillum. Despite being recognized as important
global pests, this is the first time specific molecular detection methods have
been developed that can support the early identification and detection of these
species from a broad range of environmental sample types. These fast, robust and
high-throughput assays represent powerful tools for routine marine biosecurity
surveillance, as detection and confirmation of the early presence of species
could assist in the timely establishment of emergency responses and control
strategies. This study applied the developed assays to confirm the ability to
detect Didemnid eDNA in water samples. While previous work has focused on
detection of marine larvae from water samples, the development of real-time PCR
assays specifically aimed at detecting eDNA of sessile invertebrate species in
the marine environment represents a world first and a significant step forwards
in applied marine biosecurity surveillance. Demonstrated success in the detection
of D. perlucidum eDNA from water samples at sites where it could not be visually
identified suggests value in incorporating such assays into biosecurity survey
designs targeting Didemnid species.
PMID- 27483457
TI - The carbon fertilization effect over a century of anthropogenic CO2 emissions:
higher intracellular CO2 and more drought resistance among invasive and native
grass species contrasts with increased water use efficiency for woody plants in
the US Southwest.
AB - From 1890 to 2015, anthropogenic carbon dioxide emissions have increased
atmospheric CO2 concentrations from 270 to 400 mol mol-1 . The effect of
increased carbon emissions on plant growth and reproduction has been the subject
of study of free-air CO2 enrichment (FACE) experiments. These experiments have
found (i) an increase in internal CO2 partial pressure (ci ) alongside
acclimation of photosynthetic capacity, (ii) variable decreases in stomatal
conductance, and (iii) that increases in yield do not increase commensurate with
CO2 concentrations. Our data set, which includes a 115-year-long selection of
grasses collected in New Mexico since 1892, is consistent with an increased ci as
a response to historical CO2 increase in the atmosphere, with invasive species
showing the largest increase. Comparison with Palmer Drought Sensitivity Index
(PDSI) for New Mexico indicates a moderate correlation with Delta13 C (r2 =
0.32, P < 0.01) before 1950, with no correlation (r2 = 0.00, P = 0.91) after
1950. These results indicate that increased ci may have conferred some drought
resistance to these grasses through increased availability of CO2 in the event of
reduced stomatal conductance in response to short-term water shortage. Comparison
with C3 trees from arid environments (Pinus longaeva and Pinus edulis in the US
Southwest) as well as from wetter environments (Bromus and Poa grasses in New
Mexico) suggests differing responses based on environment; arid environments in
New Mexico see increased intrinsic water use efficiency (WUE) in response to
historic elevated CO2 while wetter environments see increased ci . This study
suggests that (i) the observed increases in ci in FACE experiments are consistent
with historical CO2 increases and (ii) the CO2 increase influences plant
sensitivity to water shortage, through either increased WUE or ci in arid and wet
environments, respectively.
PMID- 27483458
TI - Ustekinumab Treatment and Improvement of Physical Function and Health-Related
Quality of Life in Patients With Psoriatic Arthritis.
AB - OBJECTIVE: To examine the effects of ustekinumab on patient-reported outcomes
(PROs) in PSUMMIT 1 and PSUMMIT 2 patients with active psoriatic arthritis (PsA)
who were methotrexate (MTX) naive, MTX experienced, or anti-tumor necrosis factor
(TNF) experienced. METHODS: Patients in the phase 3, PSUMMIT 1 (n = 615) and
PSUMMIT 2 (n = 312) studies randomly (1:1:1) received placebo, ustekinumab 45-mg,
or ustekinumab 90-mg subcutaneous injections at weeks 0, 4, 16, 28, 40, and 52.
The PROs (Health Assessment Questionnaire [HAQ] disability index [DI],
Dermatology Life Quality Index [DLQI], 36-Item Short Form [SF-36] health survey
physical (PCS) and mental component summary scores, patient assessments of pain
and disease activity, and impact of disease on productivity) were assessed at
weeks 0, 24, and 52. In these post hoc analyses, outcomes were compared between
the ustekinumab and placebo groups for 3 mutually exclusive antecedent-exposure
populations from the combined studies: MTX/anti-TNF naive (placebo, n = 56; 45
mg, n = 58; and 90 mg, n = 66), MTX experienced, biologic agent naive (placebo, n
= 192; 45 mg, n = 190; and 90 mg, n = 185), and anti-TNF experienced with or
without MTX (placebo, n = 62; 45 mg, n = 60; and 90 mg, n = 58). RESULTS: At week
24, mean improvements from baseline in HAQ DI, DLQI, and SF-36 PCS scores were
significantly greater in both ustekinumab groups versus placebo across antecedent
exposure groups. Greater proportions of ustekinumab-treated than placebo-treated
patients (all P < 0.05) had clinically meaningful improvements in HAQ DI (>=0.3),
DLQI (>=5), and SF-36 (>=5) scores at week 24, irrespective of drug exposure.
Improvements in pain, disease activity, and impact of disease on productivity
were similar, and benefits were maintained through week 52. CONCLUSION:
Significant improvements in PROs with ustekinumab versus placebo were observed in
3 antecedent-exposure populations of PsA patients, including those with prior MTX
and anti-TNF use.
PMID- 27483459
TI - Soft Ngram Representation and Modeling for Protein Remote Homology Detection.
AB - Remote homology detection represents a central problem in bioinformatics, where
the challenge is to detect functionally related proteins when their sequence
similarity is low. Recent solutions employ representations derived from the
sequence profile, obtained by replacing each amino acid of the sequence by the
corresponding most probable amino acid in the profile. However, the information
contained in the profile could be exploited more deeply, provided that there is a
representation able to capture and properly model such crucial evolutionary
information. In this paper, we propose a novel profile-based representation for
sequences, called soft Ngram. This representation, which extends the traditional
Ngram scheme (obtained by grouping N consecutive amino acids), permits
considering all of the evolutionary information in the profile: this is achieved
by extracting Ngrams from the whole profile, equipping them with a weight
directly computed from the corresponding evolutionary frequencies. We illustrate
two different approaches to model the proposed representation and to derive a
feature vector, which can be effectively used for classification using a support
vector machine (SVM). A thorough evaluation on three benchmarks demonstrates that
the new approach outperforms other Ngram-based methods, and shows very promising
results also in comparison with a broader spectrum of techniques.
PMID- 27483460
TI - Batch Mode TD($?lambda$ ) for Controlling Partially Observable Gene Regulatory
Networks.
AB - External control of gene regulatory networks (GRNs) has received much attention
in recent years. The aim is to find a series of actions to apply to a gene
regulation system making it avoid its diseased states. In this work, we propose a
novel method for controlling partially observable GRNs combining batch mode
reinforcement learning (Batch RL) and TD() algorithms. Unlike the existing
studies inferring a computational model from gene expression data, and obtaining
a control policy over the constructed model, our idea is to interpret the time
series gene expression data as a sequence of observations that the system
produced, and obtain an approximate stochastic policy directly from the gene
expression data without estimation of the internal states of the partially
observable environment. Thereby, we get rid of the most time consuming phases of
the existing studies, inferring a model and running the model for the control.
Results show that our method is able to provide control solutions for regulation
systems of several thousands of genes only in seconds, whereas existing studies
cannot solve control problems of even a few dozens of genes. Results also show
that our approximate stochastic policies are almost as good as the policies
generated by the existing studies.
PMID- 27483461
TI - Triangular Alignment (TAME): A Tensor-Based Approach for Higher-Order Network
Alignment.
AB - Network alignment has extensive applications in comparative interactomics.
Traditional approaches aim to simultaneously maximize the number of conserved
edges and the underlying similarity of aligned entities. We propose a novel
formulation of the network alignment problem that extends topological similarity
to higher-order structures and provides a new objective function that maximizes
the number of aligned substructures. This objective function corresponds to an
integer programming problem, which is NP-hard. Consequently, we identify a
closely related surrogate function whose maximization results in a tensor
eigenvector problem. Based on this formulation, we present an algorithm called
Triangular AlignMEnt (TAME), which attempts to maximize the number of aligned
triangles across networks. Using a case study on the NAPAbench dataset, we show
that triangular alignment is capable of producing mappings with high node
correctness. We further evaluate our method by aligning yeast and human
interactomes. Our results indicate that TAME outperforms the state-of-art
alignment methods in terms of conserved triangles. In addition, we show that the
number of conserved triangles is more significantly correlated, compared to the
conserved edge, with node correctness and co-expression of edges. Our formulation
and resulting algorithms can be easily extended to arbitrary motifs.
PMID- 27483462
TI - Investigation of hexagonal boron nitride as an atomically thin corrosion
passivation coating in aqueous solution.
AB - Hexagonal boron nitride (h-BN) atomic layers were utilized as a passivation
coating in this study. A large-area continuous h-BN thin film was grown on nickel
foil using a chemical vapor deposition method and then transferred onto sputtered
copper as a corrosion passivation coating. The corrosion passivation performance
in a Na2SO4 solution of bare and coated copper was investigated by
electrochemical methods including cyclic voltammetry (CV), Tafel polarization and
electrochemical impedance spectroscopy (EIS). CV and Tafel analysis indicate that
the h-BN coating could effectively suppress the anodic dissolution of copper. The
EIS fitting result suggests that defects are the dominant leakage source on h-BN
films, and improved anti-corrosion performances could be achieved by further
passivating these defects.
PMID- 27483463
TI - The Toll Signaling Pathway in the Chinese Oak Silkworm, Antheraea pernyi: Innate
Immune Responses to Different Microorganisms.
AB - The Toll pathway is one of the most important signaling pathways regulating
insect innate immunity. Spatzle is a key protein that functions as a Toll
receptor ligand to trigger Toll-dependent expression of immunity-related genes.
In this study, a novel spatzle gene (ApSPZ) from the Chinese oak silkworm
Antheraea pernyi was identified. The ApSPZ cDNA is 1065 nucleotides with an open
reading frame (ORF) of 777 bp encoding a protein of 258 amino acids. The protein
has an estimated molecular weight of 29.71 kDa and an isoelectric point (PI) of
8.53. ApSPZ is a nuclear and secretory protein with no conserved domains or
membrane helices and shares 40% amino acid identity with SPZ from Manduca sexta.
Phylogenetic analysis indicated that ApSPZ might be a new member of the Spatzle
type 1 family, which belongs to the Spatzle superfamily. The expression patterns
of several genes involved in the Toll pathway were examined at different
developmental stages and various tissues in 5th instar larvae. The examined
targets included A. pernyi spatzle, GNBP, MyD88, Tolloid, cactus and dorsalA. The
RT-PCR results showed that these genes were predominantly expressed in immune
responsive fat body tissue, indicating that the genes play a crucial role in A.
pernyi innate immunity. Moreover, A. pernyi infection with the fungus Nosema
pernyi and the gram-positive bacterium Enterococcus pernyi, but not the gram
negative bacterium Escherichia coli, activated the Toll signaling pathway. These
results represent the first study of the Toll pathway in A. pernyi, which
provides insight into the A. pernyi innate immune system.
PMID- 27483464
TI - Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A
Prognostic Modelling Study.
AB - INTRODUCTION: Over 80% of the nearly 1 million men diagnosed with prostate cancer
annually worldwide present with localised or locally advanced non-metastatic
disease. Risk stratification is the cornerstone for clinical decision making and
treatment selection for these men. The most widely applied stratification systems
use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason
grade, and clinical stage to classify patients as low, intermediate, or high
risk. There is, however, significant heterogeneity in outcomes within these
standard groupings. The International Society of Urological Pathology (ISUP) has
recently adopted a prognosis-based pathological classification that has yet to be
included within a risk stratification system. Here we developed and tested a new
stratification system based on the number of individual risk factors and
incorporating the new ISUP prognostic score. METHODS AND FINDINGS: Diagnostic
clinicopathological data from 10,139 men with non-metastatic prostate cancer were
available for this study from the Public Health England National Cancer
Registration Service Eastern Office. This cohort was divided into a training set
(n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set
(n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow
up was 6.9 y, and the primary outcome measure was prostate-cancer-specific
mortality (PCSM). An external validation cohort (n = 1,706) was also used.
Patients were first categorised as low, intermediate, or high risk using the
current three-stratum stratification system endorsed by the National Institute
for Health and Care Excellence (NICE) guidelines. The variables used to define
the groups (PSA concentration, Gleason grading, and clinical stage) were then
used to sub-stratify within each risk category by testing the individual and then
combined number of risk factors. In addition, we incorporated the new ISUP
prognostic score as a discriminator. Using this approach, a new five-stratum risk
stratification system was produced, and its prognostic power was compared against
the current system, with PCSM as the outcome. The results were analysed using a
Cox hazards model, the log-rank test, Kaplan-Meier curves, competing-risks
regression, and concordance indices. In the training set, the new risk
stratification system identified distinct subgroups with different risks of PCSM
in pair-wise comparison (p < 0.0001). Specifically, the new classification
identified a very low-risk group (Group 1), a subgroup of intermediate-risk
cancers with a low PCSM risk (Group 2, hazard ratio [HR] 1.62 [95% CI 0.96
2.75]), and a subgroup of intermediate-risk cancers with an increased PCSM risk
(Group 3, HR 3.35 [95% CI 2.04-5.49]) (p < 0.0001). High-risk cancers were also
sub-classified by the new system into subgroups with lower and higher PCSM risk:
Group 4 (HR 5.03 [95% CI 3.25-7.80]) and Group 5 (HR 17.28 [95% CI 11.2-26.67])
(p < 0.0001), respectively. These results were recapitulated in the testing set
and remained robust after inclusion of competing risks. In comparison to the
current risk stratification system, the new system demonstrated improved
prognostic performance, with a concordance index of 0.75 (95% CI 0.72-0.77)
versus 0.69 (95% CI 0.66-0.71) (p < 0.0001). In an external cohort, the new
system achieved a concordance index of 0.79 (95% CI 0.75-0.84) for predicting
PCSM versus 0.66 (95% CI 0.63-0.69) (p < 0.0001) for the current NICE risk
stratification system. The main limitations of the study were that it was
registry based and that follow-up was relatively short. CONCLUSIONS: A novel and
simple five-stratum risk stratification system outperforms the standard three
stratum risk stratification system in predicting the risk of PCSM at diagnosis in
men with primary non-metastatic prostate cancer, even when accounting for
competing risks. This model also allows delineation of new clinically relevant
subgroups of men who might potentially receive more appropriate therapy for their
disease. Future research will seek to validate our results in external datasets
and will explore the value of including additional variables in the system in
order in improve prognostic performance.
PMID- 27483465
TI - Deep Sequencing Reveals Novel Genetic Variants in Children with Acute Liver
Failure and Tissue Evidence of Impaired Energy Metabolism.
AB - BACKGROUND & AIMS: The etiology of acute liver failure (ALF) remains elusive in
almost half of affected children. We hypothesized that inherited mitochondrial
and fatty acid oxidation disorders were occult etiological factors in patients
with idiopathic ALF and impaired energy metabolism. METHODS: Twelve patients with
elevated blood molar lactate/pyruvate ratio and indeterminate etiology were
selected from a retrospective cohort of 74 subjects with ALF because their fixed
and frozen liver samples were available for histological, ultrastructural,
molecular and biochemical analysis. RESULTS: A customized next-generation
sequencing panel for 26 genes associated with mitochondrial and fatty acid
oxidation defects revealed mutations and sequence variants in five subjects.
Variants involved the genes ACAD9, POLG, POLG2, DGUOK, and RRM2B; the latter not
previously reported in subjects with ALF. The explanted livers of the patients
with heterozygous, truncating insertion mutations in RRM2B showed patchy micro-
and macrovesicular steatosis, decreased mitochondrial DNA (mtDNA) content <30% of
controls, and reduced respiratory chain complex activity; both patients had good
post-transplant outcome. One infant with severe lactic acidosis was found to
carry two heterozygous variants in ACAD9, which was associated with isolated
complex I deficiency and diffuse hypergranular hepatocytes. The two subjects with
heterozygous variants of unknown clinical significance in POLG and DGUOK
developed ALF following drug exposure. Their hepatocytes displayed abnormal
mitochondria by electron microscopy. CONCLUSION: Targeted next generation
sequencing and correlation with histological, ultrastructural and functional
studies on liver tissue in children with elevated lactate/pyruvate ratio expand
the spectrum of genes associated with pediatric ALF.
PMID- 27483466
TI - Gongjin-Dan Enhances Hippocampal Memory in a Mouse Model of Scopolamine-Induced
Amnesia.
AB - We evaluated the neuropharmacological effects of Gongjin-Dan (GJD) on the memory
impairment caused by scopolamine injection. BALB/c mice were orally treated with
GJD (100, 200, or 400 mg/kg, daily) or tacrine (THA, 10 mg/kg) for 10 days, and
scopolamine (2 mg/kg) was injected intraperitoneally. The radial arm maze and
passive avoidance tests were performed to evaluate the animal's learning and
memory. Scopolamine increased the task completing time, the number of total
errors (reference and working memory error) in the radial arm maze task, and the
latency time in the passive avoidance test, which were significantly ameliorated
by treatment with GJD. The GJD treatment also attenuated the scopolamine-induced
hyperactivation of acetylcholinesterase activity, and suppression of the
expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF)
and their receptors in the hippocampus. These effects of GJD were supported by
both the doublecortin (DCX)-positive staining and Nissl staining, which were used
to measure hippocampal neurogenesis and atrophy, respectively. These findings
strongly suggest that GJD exerts a potent anti-amnesic effect, and its underlying
mechanism might involve the modulation of cholinergic activity.
PMID- 27483467
TI - Perfectionism and Effort-Related Cardiac Activity: Do Perfectionists Try Harder?
AB - Do perfectionists try harder? Previous research on perfectionism and effort has
used self-report items and task performance as indicators of effort. The current
study investigated whether individual differences in perfectionism predicted
effort-related cardiac activity during a mental effort task. Based on past
research that suggests adaptive perfectionism is associated with higher effort,
it was hypothesized that self-oriented perfectionism (SOP) would predict
increased effort on the task. One hundred and eleven college students completed
the Multidimensional Perfectionism Scale (MPS) and a self-paced parity task in
which they received a small cash reward (3 cents) for each correct response.
Impedance cardiography was used to assess autonomic reactivity, and regression
models tested whether SOP and socially prescribed perfectionism (SPP) explained
autonomic reactivity. Overall, participants showed both sympathetic (faster pre
ejection period; PEP) and parasympathetic activation (elevated high-frequency
heart rate variability; HRV) during the task, reflecting higher effort and
engagement. Contrary to predictions, individual differences in perfectionism did
not moderate cardiac reactivity. These findings draw attention to the importance
of assessing physiological components of effort and motivation directly rather
than inferring them from task performance or self-reported effort.
PMID- 27483468
TI - PD-1 Antibody Monotherapy for Malignant Melanoma: A Systematic Review and Meta
Analysis.
AB - Antibodies targeting programmed death 1 (PD-1) help prevent tumor cells from
escaping immune-mediated destruction. We conducted this systematic review and
meta-analysis to gain insight into the efficacy of PD-1 antibodies for the
treatment of melanoma. Five trials involving 2,828 adult patients were included
in this meta-analysis. In patients with previously untreated or refractory
melanoma, treatment with PD-1 antibodies significantly improved the six-month
progression-free survival (PFS) (HR 0.55, 95% CI 0.50-0.60, P<0.00001) and the
overall response rate (OR 3.89, 95% CI 3.12-4.83, P<0.00001). This meta-analysis
indicated that anti-PD-1 treatment might provide a significant survival benefit
in patients with melanoma. In addition, we found that patients treated with
nivolumab reported significantly fewer treatment-related adverse events (OR 0.74,
95% CI 0.57-0.97, P = 0.03) than those treated with other agents, but there was a
dose-dependent increase in the frequency of adverse events in patients treated
with pembrolizumab.
PMID- 27483469
TI - CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway
Critical for Spermatogenesis.
AB - Cystic fibrosis is the most common genetic disease among Caucasians and affects
tissues including lung, pancreas and reproductive tracts. It has been shown that
Endoplasmic Reticulum (ER) stress and heat shock response are two major
deregulated functional modules related to CFTR dysfunction. To identify the
impact of CFTR deletion during spermatogenesis, we examined the expression of
spermiogenesis-related genes in the testis of CFTR mutant mice (CF mice). We
confirmed expression changes of MSY2, a germ cell specific RNA binding protein,
resulting from deletion of CFTR in testis. Furthermore, real time PCR and Western
blot results showed that an inflammatory response was activated in CF mice
testis, as reflected by the altered expression of cytokines. We demonstrate for
the first time that expression of MSY2 is decreased in CF mice. Our results
suggest that CFTR deletion in testis influences inflammatory responses and these
features are likely to be due to the unique environment of the seminiferous
tubule during the spermatogenesis process. The current study also suggests
avenues to understand the pathophysiology of CFTR during spermatogenesis and
provides targets for the possible treatment of CFTR-related infertility.
PMID- 27483470
TI - A Single-Batch Fermentation System to Simulate Human Colonic Microbiota for High
Throughput Evaluation of Prebiotics.
AB - We devised a single-batch fermentation system to simulate human colonic
microbiota from fecal samples, enabling the complex mixture of microorganisms to
achieve densities of up to 1011 cells/mL in 24 h. 16S rRNA gene sequence analysis
of bacteria grown in the system revealed that representatives of the major phyla,
including Bacteroidetes, Firmicutes, and Actinobacteria, as well as overall
species diversity, were consistent with those of the original feces. On the
earlier stages of fermentation (up to 9 h), trace mixtures of acetate, lactate,
and succinate were detectable; on the later stages (after 24 h), larger amounts
of acetate accumulated along with some of propionate and butyrate. These patterns
were similar to those observed in the original feces. Thus, this system could
serve as a simple model to simulate the diversity as well as the metabolism of
human colonic microbiota. Supplementation of the system with several prebiotic
oligosaccharides (including fructo-, galacto-, isomalto-, and xylo
oligosaccharides; lactulose; and lactosucrose) resulted in an increased
population in genus Bifidobacterium, concomitant with significant increases in
acetate production. The results suggested that this fermentation system may be
useful for in vitro, pre-clinical evaluation of the effects of prebiotics prior
to testing in humans.
PMID- 27483471
TI - Influence of LAR and VAR on Para-Aminopyridine Antimalarials Targetting Haematin
in Chloroquine-Resistance.
AB - Antimalarial chloroquine (CQ) prevents haematin detoxication when CQ-base
concentrates in the acidic digestive vacuole through protonation of its p
aminopyridine (pAP) basic aromatic nitrogen and sidechain diethyl-N. CQ export
through the variant vacuolar membrane export channel, PFCRT, causes CQ-resistance
in Plasmodium falciparum but 3-methyl CQ (sontochin SC), des-ethyl amodiaquine
(DAQ) and bis 4-aminoquinoline piperaquine (PQ) are still active. This is
determined by changes in drug accumulation ratios in parasite lipid (LAR) and in
vacuolar water (VAR). Higher LAR may facilitate drug binding to and blocking
PFCRT and also aid haematin in lipid to bind drug. LAR for CQ is only 8.3; VAR is
143,482. More hydrophobic SC has LAR 143; VAR remains 68,523. Similarly DAQ with
a phenol substituent has LAR of 40.8, with VAR 89,366. In PQ, basicity of each
pAP is reduced by distal piperazine N, allowing very high LAR of 973,492,
retaining VAR of 104,378. In another bis quinoline, dichlorquinazine (DCQ), also
active but clinically unsatisfactory, each pAP retains basicity, being insulated
by a 2-carbon chain from a proximal nitrogen of the single linking piperazine.
While LAR of 15,488 is still high, the lowest estimate of VAR approaches 4.9
million. DCQ may be expected to be very highly lysosomotropic and therefore
potentially hepatotoxic. In 11 pAP antimalarials a quadratic relationship between
logLAR and logResistance Index (RI) was confirmed, while log (LAR/VAR) vs logRI
for 12 was linear. Both might be used to predict the utility of structural
modifications.
PMID- 27483472
TI - Genetic Variation of 25 Y-Chromosomal and 15 Autosomal STR Loci in the Han
Chinese Population of Liaoning Province, Northeast China.
AB - In the present study, we investigated the genetic characteristics of 25 Y
chromosomal and 15 autosomal short tandem repeat (STR) loci in 305 unrelated Han
Chinese male individuals from Liaoning Province using AmpFISTR(r) Yfiler(r) Plus
and IdentifilerTM PCR amplification kits. Population comparison was performed
between Liaoning Han population and different ethnic groups to better understand
the genetic background of the Liaoning Han population. For Y-STR loci, the
overall haplotype diversity was 0.9997 and the discrimination capacity was
0.9607. Gene diversity values ranged from 0.4525 (DYS391) to 0.9617 (DYS385). Rst
and two multi-dimensional scaling plots showed that minor differences were
observed when the Liaoning Han population was compared to the Jilin Han Chinese,
Beijing Han Chinese, Liaoning Manchu, Liaoning Mongolian, Liaoning Xibe, Shandong
Han Chinese, Jiangsu Han Chinese, Anhui Han Chinese, Guizhou Han Chinese and
Liaoning Hui populations; by contrast, major differences were observed when the
Shanxi Han Chinese, Yunnan Bai, Jiangxi Han Chinese, Guangdong Han Chinese,
Liaoning Korean, Hunan Tujia, Guangxi Zhuang, Gansu Tibetan, Xishuangbanna Dai,
South Korean, Japanese and Hunan Miao populations. For autosomal STR loci, DP
ranged from 0.9621 (D2S1338) to 0.8177 (TPOX), with PE distributing from 0.7521
(D18S51) to 0.2988 (TH01). A population comparison was performed and no
statistically significant differences were detected at any STR loci between
Liaoning Han, China Dong, and Shaanxi Han populations. The results showed that
the 25 Y-STR and 15 autosomal STR loci in the Liaoning Han population were
valuable for forensic applications and human genetics, and Liaoning Han was an
independent endogenous ethnicity with a unique subpopulation structure.
PMID- 27483474
TI - SleepSense: A Noncontact and Cost-Effective Sleep Monitoring System.
AB - Quality of sleep is an important indicator of health and well being. Recent
developments in the field of in-home sleep monitoring have the potential to
enhance a person's sleeping experience and contribute to an overall sense of well
being. Existing in-home sleep monitoring devices either fail to provide adequate
sleep information or are obtrusive to use. To overcome these obstacles, a
noncontact and cost-effective sleep monitoring system, named SleepSense, is
proposed for continuous recognition of the sleep status, including on-bed
movement, bed exit, and breathing section. SleepSense consists of three parts: a
Doppler radar-based sensor, a robust automated radar demodulation module, and a
sleep status recognition framework. Herein, several time-domain and frequency
domain features are extracted for the sleep recognition framework. A prototype of
SleepSense is presented and evaluated using two sets of experiments. In the short
term controlled experiment, the SleepSense achieves an overall 95.1% accuracy
rate in identifying various sleep status. In the 75-minute sleep study,
SleepSense demonstrates wide usability in real life. The error rate for breathing
rate extraction in this study is only 6.65%. These experimental results indicate
that SleepSense is an effective and promising solution for in-home sleep
monitoring.
PMID- 27483473
TI - How Quorum Sensing Connects Sporulation to Necrotrophism in Bacillus
thuringiensis.
AB - Bacteria use quorum sensing to coordinate adaptation properties, cell fate or
commitment to sporulation. The infectious cycle of Bacillus thuringiensis in the
insect host is a powerful model to investigate the role of quorum sensing in
natural conditions. It is tuned by communication systems regulators belonging to
the RNPP family and directly regulated by re-internalized signaling peptides. One
such RNPP regulator, NprR, acts in the presence of its cognate signaling peptide
NprX as a transcription factor, regulating a set of genes involved in the
survival of these bacteria in the insect cadaver. Here, we demonstrate that, in
the absence of NprX and independently of its transcriptional activator function,
NprR negatively controls sporulation. NprR inhibits expression of Spo0A-regulated
genes by preventing the KinA-dependent phosphorylation of the phosphotransferase
Spo0F, thus delaying initiation of the sporulation process. This NprR function
displays striking similarities with the Rap proteins, which also belong to the
RNPP family, but are devoid of DNA-binding domain and indirectly control gene
expression via protein-protein interactions in Bacilli. Conservation of the Rap
residues directly interacting with Spo0F further suggests a common inhibition of
the sporulation phosphorelay. The crystal structure of apo NprR confirms that
NprR displays a highly flexible Rap-like structure. We propose a molecular
regulatory mechanism in which key residues of the bifunctional regulator NprR are
directly and alternatively involved in its two functions. NprX binding switches
NprR from a dimeric inhibitor of sporulation to a tetrameric transcriptional
activator involved in the necrotrophic lifestyle of B. thuringiensis. NprR thus
tightly coordinates sporulation and necrotrophism, ensuring survival and
dissemination of the bacteria during host infection.
PMID- 27483475
TI - Body-Earth Mover's Distance: A Matching-Based Approach for Sleep Posture
Recognition.
AB - Sleep posture is a key component in sleep quality assessment and pressure ulcer
prevention. Currently, body pressure analysis has been a popular method for sleep
posture recognition. In this paper, a matching-based approach, Body-Earth Mover's
Distance (BEMD), for sleep posture recognition is proposed. BEMD treats pressure
images as weighted 2D shapes, and combines EMD and Euclidean distance for
similarity measure. Compared with existing work, sleep posture recognition is
achieved with posture similarity rather than multiple features for specific
postures. A pilot study is performed with 14 persons for six different postures.
The experimental results show that the proposed BEMD can achieve 91.21% accuracy,
which outperforms the previous method with an improvement of 8.01%.
PMID- 27483476
TI - Computer simulations of the interaction of human immunodeficiency virus (HIV)
aspartic protease with spherical gold nanoparticles: implications in acquired
immunodeficiency syndrome (AIDS).
AB - The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus
aspartic protease (HIVPR) is modelled using a regime of molecular dynamics
simulations. The simulations of the 'docking', first as a rigid-body complex, and
eventually through flexible-fit analysis, creates 36 different complexes from
four initial orientations of the nanoparticle strategically positioned around the
surface of the enzyme. The structural deviations of the enzymes from the initial
x-ray crystal structure during each docking simulation are assessed by
comparative analysis of secondary structural elements, root mean square
deviations, B-factors, interactive bonding energies, dihedral angles, radius of
gyration (R g), circular dichroism (CD), volume occupied by C alpha ,
electrostatic potentials, solvation energies and hydrophobicities. Normalisation
of the data narrows the selection from the initial 36 to one 'final' probable
structure. It is concluded that, after computer simulations on each of the 36
initial complexes incorporating the 12 different biophysical techniques, the top
five complexes are the same no matter which technique is explored. The
significance of the present work is an expansion of an earlier study on the
molecular dynamic simulation for the interaction of HIVPR with silver
nanoparticles. This work is supported by experimental evidence since the initial
'orientation' of the AgNP with the enzyme is the same as the 'final' AuNP-HIVPR
complex generated in the present study. The findings will provide insight into
the forces of the binding of the HIVPR to AuNP. It is anticipated that the
protocol developed in this study will act as a standard process for the
interaction of any nanoparticle with any biomedical target.
PMID- 27483477
TI - Clinical relevance of isolated prolongation of the activated partial
thromboplastin time in a cohort of adults undergoing surgical procedures.
AB - BACKGROUND: Coagulation screening prior to surgery is performed routinely
worldwide to identify patients at risk of bleeding during the procedure. Evidence
from medical and surgical literature suggests that the activated partial
thromboplastin time (aPTT) alone is suitable for predicting individual bleeding
risk during surgery and it is current practice in our hospital to measure this
parameter. MATERIALS AND METHODS: We retrospectively reviewed aPTT ratio results
in 8,069 consecutive adult subjects undergoing elective surgery from January 1 to
December 31, 2014 to confirm the validity of this approach. RESULTS: In 7,606
patients (94.2%) the aPTT ratio was within the normal range while it was abnormal
in 463 (5.8%). Out of these 463, 223 aPTT ratios were between 1.2 and 1.3 and we
considered these results not worthy enough of further investigations. In 240
patients the aPTT ratio was higher than 1.3; in the vast majority of these cases
(201/240; 83%) this abnormality was associated with oral anticoagulant treatment.
Seventeen of the other 39 cases underwent detailed investigations which revealed
lupus anticoagulant (n=7), decompensated chronic liver disease (n=4), factor XII
deficiency (n=3), mild combined reduction of FXI and FXII (n=1) and mild
haemophilia A (n=2). The other 22 patients underwent successful surgery without
further investigation. DISCUSSION: Our results from a pre-surgical setting seem
to confirm the low prevalence of coagulation defects in the general population.
Increased aPTT ratios were mainly attributable to oral anticoagulant therapy,
with a few cases caused by mild, clinically irrelevant clotting factor
deficiencies. A carefully taken personal history, including medications (i.e.
oral anticoagulants) and/or previous bleeding symptoms seem more useful than
coagulation screening tests to predict the risk of bleeding.
PMID- 27483478
TI - Borrowing (once again) from the animal kingdom.
PMID- 27483479
TI - Anticoagulants for the prevention and treatment of catheter-related thrombosis in
adults and children on parenteral nutrition: a systematic review and critical
appraisal.
AB - BACKGROUND: Patients on parenteral nutrition require a central venous access and
are at risk of catheter-related thrombosis, pulmonary embolism, and vena cava
syndrome. Parenteral nutrition guidelines suggest anticoagulation for the primary
prevention of catheter-related thrombosis during long-term parenteral nutrition.
We conducted a systematic review of the efficacy, safety and feasibility of
anticoagulant use for preventing and treating catheter-related thrombosis during
parenteral nutrition. MATERIALS AND METHODS: We searched for interventional and
observational studies on adults and children receiving systemic anticoagulants
during either short- or long-term parenteral nutrition delivered via central
venous access. Primary outcomes were: objectively-confirmed catheter-related
thrombosis, pulmonary embolism and bleeding. Secondary outcomes were: heparin
induced thrombocytopenia, prevalence of anticoagulation, and quality of
International Normalised Ratio management in vitamin K antagonist-treated
patients. RESULTS: We identified 1,199 studies, of which 23 were included. Seven
interventional studies of short-term parenteral nutrition (adult population, n=5)
were classified as low-quality: in those, intravenous unfractionated heparin did
not prevent catheter-related thrombosis if compared to saline. No interventional
studies were conducted in patients on long-term parenteral nutrition.
Observational data were sparse, rarely focusing on anticoagulation, and overall
of low quality. The reported use of anticoagulants was between 22 and 66% in
recent multicentre cohorts. DISCUSSION: The amount and quality of data in this
area are very suboptimal: most studies are outdated and involved heterogeneous
populations. Currently, there is insufficient evidence to allow conclusions to be
reached regarding the efficacy and safety of anticoagulants in this setting.
PMID- 27483481
TI - The relative efficacy of three interventions to favour return to give blood.
AB - BACKGROUND: The aim of the study was to test the relative efficacy of action
planning and reward distribution to promote retention of whole blood donors.
MATERIALS AND METHODS: A sample of 7,399 donors was randomised to one of three
interventions: "action planning" (n=2,585); "reward" (n=2,397); and "thank you"
(n=2,417). Participants in the action planning condition were invited to write
the date of their next donation on a post-it note before taking it home at the
end of the donation process. Participants in the "reward" condition were given an
anti-theft credit card sleeve at the end of the donation process. The "thank you"
intervention is the usual condition at the end of the process; it was considered
the control condition. The dependent variable was the proportion of donors who
registered to give blood at six months. RESULTS: Overall, 4,444 (60.06%) donors
registered to give blood at six months. There were no differences between the
three interventions in the proportions of donors who registered to give blood
(d.f. 2, chi-square=3.72, p<0.15). However, gender modified the effect of the
intervention (d.f. 2, chi-square=6.57, p<0.0375); more women registered in the
"thank you" condition than in the other two. DISCUSSION: The results suggest that
action planning and the distribution of a reward have no motivational effect on
the return to give blood. Nonetheless, women appear to respond more negatively to
these interventions at the end of the donation process.
PMID- 27483480
TI - Molecular immunohaematology round table discussions at the AABB Annual Meeting,
Anaheim 2015.
PMID- 27483482
TI - Platelet gel: a new therapeutic tool with great potential.
AB - Chronic wounds, such as diabetic foot ulcers, represent a serious clinical
problem for patients and clinicians. Management of these wounds has a strong
economic impact worldwide. Complications resulting from injuries are a frequent
cause of morbidity and mortality. Chronic wounds lead to infections, painful
dressings and prolonged hospitalisation. This results in poor patient Quality of
Life and in high healthcare costs. Platelet concentrates (PC) are defined as
autologous or allogeneic platelet derivatives with a platelet concentration
higher than baseline. PC are widely used in different areas of Regenerative
Medicine in order to enhance wound healing processes; they include platelet-rich
plasma (PRP), platelet gel (PG), platelet-rich fibrin (PRF), serum eye drops (E
S), and PRP eye drops (E-PRP). This review highlights the use of platelet-rich
plasma (PRP) and platelet gel (PG) preparation for clinical use.
PMID- 27483483
TI - Intravenous iron supplementation with intra-articular administration of
tranexamic acid reduces the rate of allogeneic transfusions after simultaneous
bilateral total knee arthroplasty.
AB - BACKGROUND: Peri-operative intravenous administration of iron supplementation
seems a good option to reduce allogeneic blood transfusion in major orthopaedic
surgery. However, its efficacy in simultaneous bilateral total knee arthroplasty
has not been studied. MATERIALS AND METHODS: From December 2014 to May 2015, a
total of 72 consecutive patients underwent simultaneous bilateral total knee
arthroplasty and received peri-operative intravenous iron supplementation (iron
isomaltoside 1000: 600 mg pre-operatively and 400 mg 1 week post-operatively) and
intra-articular tranexamic acid (2 g in 20 mL saline at the end of surgery), and
were managed with a restrictive transfusion trigger (haemoglobin <7 g/dL). Post
operatively, we observed patients closely for symptoms of anaemia and checked
their haemoglobin levels on days 1, 6 and 13 after surgery. RESULTS: The mean
baseline haemoglobin level was 13.1 g/dL. The levels remained above 7.0 g/dL on
post-operative days 1, 6 and 13 (mean, 11.4 g/dL, 9.9 g/dL and 10.4 g/dL,
respectively) in all but one patient who experienced melaena and required
allogeneic blood transfusion. DISCUSSION: Intravenous iron supplementation
combined with intra-articular administration of tranexamic acid seems to be an
effective strategy for reducing the rate of allogeneic blood transfusion in
patients undergoing simultaneous bilateral total knee arthroplasty managed with a
restrictive transfusion trigger.
PMID- 27483484
TI - Porcine recombinant factor VIII: an additional weapon to handle anti-factor VIII
antibodies.
AB - This review focuses on the use of recombinant porcine factor VIII (FVIII) for the
treatment of bleeding episodes in patients with severe haemophilia A complicated
by inhibitors and in those with acquired haemophilia A due to the onset of anti
FVIII autoantibodies. We present the main characteristics of recombinant porcine
factor VIII (FVIII) and provide a summary of the published results of the
clinical studies of this novel recombinant FVIII. There is a special emphasis on
how the use of recombinant porcine factor VIII (FVIII) is expected to improve the
clinical management of these patients.
PMID- 27483485
TI - The increased demand for plasma-derived factor VIII in Italy.
PMID- 27483486
TI - Quality indicators for Transfusion Medicine in Spain: a survey among hospital
transfusion services.
AB - BACKGROUND: Transfusion services in the European Union must implement quality
management systems to improve quality. Quality indicators (QI) play a key role in
quality management because they can supply important information about the
performance of the transfusion service, which can then be used for benchmarking.
However, little is known about the actual use of QI in hospitals. We tried to
ascertain the use and characteristics of QI in Spanish hospital transfusion
services. MATERIALS AND METHODS: We performed a survey among transfusion services
in order to learn which QI they use. We classified indicators into categories and
concepts, according to the steps of the transfusion process or the activities the
indicators referred to. RESULTS: Seventy-six hospitals (17.9% of the hospitals
actively transfusing in the country) reported 731 QI. Twenty-two of them (29%)
were tertiary level hospitals. The number of indicators per hospital and by
activity varied greatly. QI were assigned to some basic categories: transfusion
process (23% of indicators), transfusion activity and stock management (22%),
haemovigilance (20%), stem cell transplantation (9%), transfusion laboratory
(9%), quality management system (8%), blood donation (3.4%), apheresis and
therapeutic activities (2.5%) and immunohaematology of pregnancy (2%).
DISCUSSION: Although most hospitals use QI in their quality management system and
share a core group of indicators, we found a great dispersion in the number and
characteristics of the indicators used. The use of a commonly agreed set of QI
could be an aid to benchmarking among hospitals and to improving the transfusion
process.
PMID- 27483487
TI - Functional characterisation of the type 1 von Willebrand disease candidate VWF
gene variants: p.M771I, p.L881R and p.P1413L.
AB - BACKGROUND: Abnormalities in the biosynthetic pathway or increased clearance of
plasma von Willebrand factor (VWF) are likely to contribute to decreased plasma
VWF levels in inherited type 1 von Willebrand disease (VWD). Recent studies
demonstrated that 65% of type 1 VWD patients have candidate VWF mutations, the
majority of which are missense variants. The purpose of this study was to explore
the effects of three VWF missense mutations (p.M771I, p.L881R and p.P1413L)
located in different functional domains of VWF, reported as candidate mutations
in type 1 VWD patients in the course of the MCMDM-1VWD study. MATERIALS AND
METHODS: The focus of these studies was on the intracellular biosynthetic
processing and localisation of VWF in a heterologous cell system. Molecular
dynamic simulation for p.M771I and p.P1413L was also performed to analyse the
conformational effects of the changes. RESULTS: As determined by
immunofluorescence antibody staining and confocal microscopy of HEK293 cells, the
intracellular localisation of recombinant VWF with the p.M771I variation was
impaired. Transient transfection studies and phorbol myristate acetate
stimulation in COS-7 cells revealed significant intracellular retention. In
addition, major loss of VWF multimers was observed for only the p.M771I mutation.
Molecular dynamic simulations on p.M771I mutant VWF revealed distinct structural
rearrangements including a large deviation in the E' domain, and significant loss
of beta-sheet secondary structure. DISCUSSION: The pathogenic effects of
candidate VWF gene mutations were explored in this study. In vitro expression
studies in heterologous cell systems revealed impaired secretion of VWF and a
dominant negative effect on the processing of the wild-type protein for only the
p.M771I mutation and none of the mutations affected the regulated secretion.
PMID- 27483489
TI - 27 Congreso Anual de la SETS: Bilbao (Espana), 23-25 Junio 2016.
PMID- 27483488
TI - Hepatitis E virus infections in travellers: assessing the threat to the
Australian blood supply.
AB - BACKGROUND: In many developed countries hepatitis E virus (HEV) infections have
occurred predominantly in travellers to countries endemic for HEV. HEV is a
potential threat to blood safety as the virus is transfusion-transmissible. To
minimise this risk in Australia, individuals diagnosed with HEV are deferred.
Malarialdeferrals, when donors are restricted from donating fresh blood
components following travel toanareain which malaria is endemic, probably also
decrease the HEV risk, by deferring donors who travel to many countries also
endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases
in Australia, in order to determine whether infection in travellers poses a risk
to Australian blood safety. MATERIALS AND METHODS: Details of all notified HEV
cases in Australia from 2002 to 2014 were accessed, and importation rates
estimated. Countries in which HEV was acquired were compared to those for which
donations are restricted following travel because of a malaria risk. RESULTS:
Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India
accounted for most of these infections, although the importation rate was highest
for Nepal and Bangladesh. Countries for which donations are restricted following
travel due to malaria risk accounted for 94% of overseas-acquired HEV cases.
DISCUSSION: The vast majority of overseas-acquired HEV infections were in
travellers returning from South Asian countries, which are subject to donation
related travel restrictions for malaria. This minimises the risk HEV poses to the
Australian blood supply.
PMID- 27483490
TI - Physical-Perceptual Correspondence for Dynamic Thermal Stimulation.
AB - Thermal displays have been applied in various haptic applications, from material
simulation to interpersonal communication; however, there is insufficient
knowledge about the temporal processing in human thermal sense to provide a
knowledge basis for thermal display design. In this study, we investigated the
physical-perceptual correspondence for dynamic thermal stimulation to shed a
light on the temporal processing of human thermal sense. In the experiments,
participants reported subjective timings of the temperature onset and temperature
peak of continuous temperature changes applied to the thenar eminence. We found
that the physical-perceptual correspondence was not consistent for warm and cold
stimulations. For warm stimulation, the subjective experience always came after
the corresponding physical event. On the other hand, for cold stimulation, while
the subjective onset always lagged the physical onset, the subjective temperature
peak preceded the physical temperature peak. We analyzed these results in the
framework of linear systems theory. The results suggest that the senses of warmth
and cold have distinct temporal filtering properties, with the sense of cold
being more transient than the sense of warmth. These findings advance our
knowledge regarding temporal processing in human thermal sense and serve as a
basis for thermal display design.
PMID- 27483491
TI - Hierarchical Address Event Routing for Reconfigurable Large-Scale Neuromorphic
Systems.
AB - We present a hierarchical address-event routing (HiAER) architecture for scalable
communication of neural and synaptic spike events between neuromorphic
processors, implemented with five Xilinx Spartan-6 field-programmable gate arrays
and four custom analog neuromophic integrated circuits serving 262k neurons and
262M synapses. The architecture extends the single-bus address-event
representation protocol to a hierarchy of multiple nested buses, routing events
across increasing scales of spatial distance. The HiAER protocol provides
individually programmable axonal delay in addition to strength for each synapse,
lending itself toward biologically plausible neural network architectures, and
scales across a range of hierarchies suitable for multichip and multiboard
systems in reconfigurable large-scale neuromorphic systems. We show approximately
linear scaling of net global synaptic event throughput with number of routing
nodes in the network, at 3.6*107 synaptic events per second per 16k-neuron node
in the hierarchy.
PMID- 27483492
TI - 3D Ta/TaO x /TiO2/Ti synaptic array and linearity tuning of weight update for
hardware neural network applications.
AB - The implementation of highly anticipated hardware neural networks (HNNs) hinges
largely on the successful development of a low-power, high-density, and reliable
analog electronic synaptic array. In this study, we demonstrate a two-layer
Ta/TaO x /TiO2/Ti cross-point synaptic array that emulates the high-density three
dimensional network architecture of human brains. Excellent uniformity and
reproducibility among intralayer and interlayer cells were realized. Moreover, at
least 50 analog synaptic weight states could be precisely controlled with minimal
drifting during a cycling endurance test of 5000 training pulses at an operating
voltage of 3 V. We also propose a new state-independent bipolar-pulse-training
scheme to improve the linearity of weight updates. The improved linearity
considerably enhances the fault tolerance of HNNs, thus improving the training
accuracy.
PMID- 27483493
TI - Interval-Valued Model Level Fuzzy Aggregation-Based Background Subtraction.
AB - In a recent work, the effectiveness of neighborhood supported model level fuzzy
aggregation was shown under dynamic background conditions. The multi-feature
fuzzy aggregation used in that approach uses real fuzzy similarity values, and is
robust for low and medium-scale dynamic background conditions such as swaying
vegetation, sprinkling water, etc. The technique, however, exhibited some
limitations under heavily dynamic background conditions, as features have high
uncertainty under such noisy conditions and these uncertainties were not captured
by real fuzzy similarity values. Our proposed algorithm is particularly focused
toward improving the detection under heavy dynamic background conditions by
modeling uncertainties in the data by interval-valued fuzzy set. In this paper,
real-valued fuzzy aggregation has been extended to interval-valued fuzzy
aggregation by considering uncertainties over real similarity values. We build up
a procedure to calculate the uncertainty that varies for each feature, at each
pixel, and at each time instant. We adaptively determine membership values at
each pixel by the Gaussian of uncertainty value instead of fixed membership
values used in recent fuzzy approaches, thereby, giving importance to a feature
based on its uncertainty. Interval-valued Choquet integral is evaluated using
interval similarity values and the membership values in order to calculate
interval-valued fuzzy similarity between model and current. Adequate qualitative
and quantitative studies are carried out to illustrate the effectiveness of the
proposed method in mitigating heavily dynamic background situations as compared
to state-of-the-art.
PMID- 27483494
TI - Pinning Control of Lag-Consensus for Second-Order Nonlinear Multiagent Systems.
AB - Lag consensus means that the corresponding state vectors of the followers are
behind the leader with a lag time. In this paper, Lyapunov functional and matrix
theory are applied to analyze pinning-controlled lag consensus of second-order
nonlinear multiagent systems. The focus is twofold: 1) to find out which agents
should be pinned and 2) to determine what the coupling strength should be, so
that the multiagent systems can reach lag consensus. Moreover, the practical
problem in a noisy environment is considered. Finally, an illustrative example is
provided to demonstrate the effectiveness of the proposed pinning control
protocol.
PMID- 27483495
TI - Dynamics of Metabolism and Decision Making During Alcohol Consumption: Modeling
and Analysis.
AB - Heavy alcohol consumption is considered an important public health issue in the
United States as over 88 000 people die every year from alcohol-related causes.
Research is being conducted to understand the etiology of alcohol consumption and
to develop strategies to decrease high-risk consumption and its consequences, but
there are still important gaps in determining the main factors that influence the
consumption behaviors throughout the drinking event. There is a need for
methodologies that allow us not only to identify such factors but also to have a
comprehensive understanding of how they are connected and how they affect the
dynamical evolution of a drinking event. In this paper, we use previous empirical
findings from laboratory and field studies to build a mathematical model of the
blood alcohol concentration dynamics in individuals that are in drinking events.
We characterize these dynamics as the result of the interaction between a
decision-making system and the metabolic process for alcohol. We provide a model
of the metabolic process for arbitrary alcohol intake patterns and a
characterization of the mechanisms that drive the decision-making process of a
drinker during the drinking event. We use computational simulations and Lyapunov
stability theory to analyze the effects of the parameters of the model on the
blood alcohol concentration dynamics that are characterized. Also, we propose a
methodology to inform the model using data collected in situ and to make
estimations that provide additional information to the analysis. We show how this
model allows us to analyze and predict previously observed behaviors, to design
new approaches for the collection of data that improves the construction of the
model, and help with the design of interventions.
PMID- 27483496
TI - School Siting Near Industrial Chemical Facilities: Findings from the U.S.
Chemical Safety Board's Investigation of the West Fertilizer Explosion.
AB - BACKGROUND: The U.S. Chemical Safety and Hazard Investigation Board (CSB)
investigated the 17 April 2013 explosion at the West Fertilizer Company (WFC)
that resulted in 15 fatalities, more than 260 injuries, and damage to more than
150 buildings. Among these structures were four nearby school buildings
cumulatively housing children in grades kindergarten-12, a nursing care facility,
and an apartment complex. The incident occurred during the evening when school
was not in session, which reduced the number of injuries. OBJECTIVES: The goal of
this commentary is to illustrate the consequences of siting schools near
facilities that store or use hazardous chemicals, and highlight the need for
additional regulations to prevent future siting of schools near these facilities.
DISCUSSION: We summarize the findings of the CSB's investigation related to the
damaged school buildings and the lack of regulation surrounding the siting of
schools near facilities that store hazardous chemicals. CONCLUSIONS: In light of
the current lack of federal authority for oversight of land use near educational
institutions, state and local governments should take a proactive role in
promulgating state regulations that prohibit the siting of public receptors, such
as buildings occupied by children, near facilities that store hazardous
chemicals. CITATION: Tinney VA, Denton JM, Sciallo-Tyler L, Paulson JA. 2016.
School siting near industrial chemical facilities: findings from the U.S.
Chemical Safety Board's investigation of the West Fertilizer Explosion. Environ
Health Perspect 124:1493-1496; http://dx.doi.org/10.1289/EHP132.
PMID- 27483497
TI - Modeling human diseases: an education in interactions and interdisciplinary
approaches.
AB - Traditionally, most investigators in the biomedical arena exploit one model
system in the course of their careers. Occasionally, an investigator will switch
models. The selection of a suitable model system is a crucial step in research
design. Factors to consider include the accuracy of the model as a reflection of
the human disease under investigation, the numbers of animals needed and ease of
husbandry, its physiology and developmental biology, and the ability to apply
genetics and harness the model for drug discovery. In my lab, we have primarily
used the zebrafish but combined it with other animal models and provided a
framework for others to consider the application of developmental biology for
therapeutic discovery. Our interdisciplinary approach has led to many insights
into human diseases and to the advancement of candidate drugs to clinical trials.
Here, I draw on my experiences to highlight the importance of combining multiple
models, establishing infrastructure and genetic tools, forming collaborations,
and interfacing with the medical community for successful translation of basic
findings to the clinic.
PMID- 27483498
TI - Show and tell: disclosure and data sharing in experimental pathology.
AB - Reproducibility of data from experimental investigations using animal models is
increasingly under scrutiny because of the potentially negative impact of poor
reproducibility on the translation of basic research. Histopathology is a key
tool in biomedical research, in particular for the phenotyping of animal models
to provide insights into the pathobiology of diseases. Failure to disclose and
share crucial histopathological experimental details compromises the validity of
the review process and reliability of the conclusions. We discuss factors that
affect the interpretation and validation of histopathology data in publications
and the importance of making these data accessible to promote replicability in
research.
PMID- 27483499
TI - Evaluating the Impact of the U.S. National Toxicology Program: A Case Study on
Hexavalent Chromium.
AB - BACKGROUND: Evaluating the impact of federally funded research with a broad,
methodical, and objective approach is important to ensure that public funds
advance the mission of federal agencies. OBJECTIVES: We aimed to develop a
methodical approach that would yield a broad assessment of National Toxicology
Program's (NTP's) effectiveness across multiple sectors and demonstrate the
utility of the approach through a case study. METHODS: A conceptual model was
developed with defined activities, outputs (products), and outcomes (proximal,
intermediate, distal) and applied retrospectively to NTP's research on hexavalent
chromium (CrVI). Proximal outcomes were measured by counting views of and
requests for NTP's products by external stakeholders. Intermediate outcomes were
measured by bibliometric analysis. Distal outcomes were assessed through Web and
LexisNexis searches for documents related to legislation or regulation changes.
RESULTS: The approach identified awareness of NTP's work on CrVI by external
stakeholders (proximal outcome) and citations of NTP's research in scientific
publications, reports, congressional testimonies, and legal and policy documents
(intermediate outcome). NTP's research was key to the nation's first-ever
drinking water standard for CrVI adopted by California in 2014 (distal outcome).
By applying this approach to a case study, the utility and limitations of the
approach were identified, including challenges to evaluating the outcomes of a
research program. CONCLUSIONS: This study identified a broad and objective
approach for assessing NTP's effectiveness, including methodological needs for
more thorough and efficient impact assessments in the future. Citation: Xie Y,
Holmgren S, Andrews DMK, Wolfe MS. 2017. Evaluating the impact of the U.S.
National Toxicology Program: a case study on hexavalent chromium. Environ Health
Perspect 125:181-188; http://dx.doi.org/10.1289/EHP21.
PMID- 27483501
TI - Crisis Standards of Care: A Systems Framework for Catastrophic Disaster Response.
PMID- 27483500
TI - Residential Exposure to Natural Background Radiation and Risk of Childhood Acute
Leukemia in France, 1990-2009.
AB - BACKGROUND: Exposures to high-dose ionizing radiation and high-dose rate ionizing
radiation are established risk factors for childhood acute leukemia (AL). The
risk of AL following exposure to lower doses due to natural background radiation
(NBR) has yet to be conclusively determined. METHODS: AL cases diagnosed over
1990-2009 (9,056 cases) were identified and their municipality of residence at
diagnosis collected by the National Registry of Childhood Cancers. The Geocap
study, which included the 2,763 cases in 2002-2007 and 30,000 population
controls, was used for complementary analyses. NBR exposures were modeled on a
fine scale (36,326 municipalities) based on measurement campaigns and geological
data. The power to detect an association between AL and dose to the red bone
marrow (RBM) fitting UNSCEAR (United Nations Scientific Committee on the Effects
of Atomic Radiation) predictions was 92%, 45% and 99% for exposure to natural
gamma radiation, radon and total radiation, respectively. RESULTS: AL risk,
irrespective of subtype and age group, was not associated with the exposure of
municipalities to radon or gamma radiation in terms of yearly exposure at age
reached, cumulative exposure or RBM dose. There was no confounding effect of
census-based socio-demographic indicators, or environmental factors (road
traffic, high voltage power lines, vicinity of nuclear plants) related to AL in
the Geocap study. CONCLUSIONS: Our findings do not support the hypothesis that
residential exposure to NBR increases the risk of AL, despite the large size of
the study, fine scale exposure estimates and wide range of exposures over France.
However, our results at the time of diagnosis do not rule out a slight
association with gamma radiation at the time of birth, which would be more in
line with the recent findings in the UK and Switzerland.
PMID- 27483502
TI - Healing the Wounds After the Fight: Army Medical Care to Repatriated Captives,
Part II.
PMID- 27483503
TI - 10-Pound Weight Loss and Lower Abdominal Pain.
PMID- 27483504
TI - A New Era of Partnership Between The Uniformed Services University and The Armed
Forced Medical College, Pune, India.
PMID- 27483505
TI - Waiting for the Cry.
PMID- 27483506
TI - The Impact of Combat Deployment on Health Care Provider Burnout in a Military
Emergency Department: A Cross-Sectional Professional Quality of Life Scale V
Survey Study.
AB - BACKGROUND: Compassion fatigue is a problem for many health care providers
manifesting as physical, mental, and spiritual exhaustion. Our objective was to
evaluate the association between prior combat deployment and compassion fatigue
among military emergency medicine providers. METHODS: We conducted a
nonexperimental cross-sectional survey of health care providers assigned to the
San Antonio Military Medical Center, Department of Emergency Medicine. We used
the Professional Quality of Life Scale V survey instrument that evaluates
provider burnout, secondary traumatic stress, and compassion satisfaction.
Outcomes included burnout, secondary traumatic stress, and compassion
satisfaction raw scores. Scores were compared between providers based on previous
combat deployments using two-tailed independent sample t tests and multiple
regression models. RESULTS: Surveys were completed by 105 respondents: 42 nurses
(20 previously deployed), 30 technicians (11 previously deployed), and 33
physicians (16 previously deployed). No statistically significant differences in
burnout, secondary traumatic stress, or compassion satisfaction scores were
detected between previously deployed providers versus providers not previously
deployed. DISCUSSION: There was no association between previous combat deployment
and emergency department provider burnout, secondary traumatic stress, or
compassion satisfaction scores.
PMID- 27483507
TI - A Qualitative Study of Male Veterans' Violence Perpetration and Treatment
Preferences.
AB - Prevention and treatment of intimate partner violence (IPV) has increasingly
focused on engaging men; however, very little work has examined how men manage
the negative emotions associated with relationship conflict, as well as their
preferences for and perceived barriers to treatment. Given the overrepresentation
of IPV among men with post-traumatic stress disorder, the perspectives of male
veterans with and without post-traumatic stress disorder are critical to
informing IPV prevention and treatment within the Veterans Administration (VA)
healthcare system. This qualitative study involved interviews with 25 male
veterans who reported recent IPV perpetration. Interview themes included coping
with emotions associated with violence and preferences and barriers to seeking
treatment related to IPV. Results found the participants were interested in
receiving IPV treatment at the Veterans Administration, and interviews offered
several suggestions for developing or adapting prevention and treatment options
for male veterans and their families to take into account violence in their
relationships.
PMID- 27483508
TI - Seeking Safety Pilot Outcome Study at Walter Reed National Military Medical
Center.
AB - Post-traumatic stress disorder (PTSD) and substance use disorder are two of the
most prominent psychiatric disorders among military service members. Seeking
Safety (SS) is an evidence-based behavioral therapy model for this comorbidity.
This article reports results of a study of SS conducted in a military setting.
Our pilot trial addressed outcomes, feasibility, and satisfaction. SS was
conducted as is to evaluate its impact without adaptation for military culture.
The sample was 24 outpatient service members (from the Army, Navy, Air Force, and
Marines) with 33% minority representation. Inclusion criteria were current PTSD
and/or SUD. Ten clinicians participated in this study after receiving SS
training. Results showed significant improvements on most outcomes, including
substance use on the Brief Addiction Monitor; PTSD symptoms on the PTSD Checklist
Military Version (total and criterion D); and the Trauma Symptom Checklist-40
(sexual abuse trauma index and anxiety subscale); functioning on the Sheehan
Disability Scale (total and family subscale); psychopathology on the Zung
Depression Scale total; the Behavior and Symptom Identification Scale (BASIS)-24
(total and subscales depression functioning, emotional liability, and psychosis);
and the Brief Symptom Inventory-18 (total and anxiety subscale); and coping on
the Coping Self-Efficacy Scale (total). Satisfaction was strong. Discussion
includes methodology limitations and next steps.
PMID- 27483509
TI - Dialectical Behavior Therapy Training and Desired Resources for Implementation:
Results From a National Program Evaluation in the Veterans Health Administration.
AB - CONTEXT: Little is known about nonresearch training experiences of providers who
implement evidence-based psychotherapies for suicidal behaviors among veterans.
EVIDENCE ACQUISITION: This national program evaluation identified the history of
training, training needs, and desired resources of clinicians who work with at
risk veterans in a national health care system. This sequential mixed methods
national program evaluation used a post-only survey design to obtain needs
assessment data from clinical sites (N = 59) within Veterans Health
Administration (VHA) facilities that implemented dialectical behavior therapy
(DBT). Data were also collected on resources preferred to support ongoing use of
DBT. RESULTS: While only 33% of clinical sites within VHA facilities reported
that staff attended a formal DBT intensive training workshop, nearly 97% of
participating sites reported having staff who completed self-study using DBT
manuals. Mobile apps for therapists and clients and templates for documentation
in the electronic health records to support measurement-based care were desired
clinical resources. CONCLUSION: Results indicate that less-intensive training
models can aid staff in implementing DBT in real-world health care settings.
While more training is requested, a number of VHA facilities have successfully
implemented DBT into the continuum of care for veterans at risk for suicide.
PMID- 27483510
TI - Effect of Uniform Design on the Speed of Combat Tourniquet Application: A
Simulation Study.
AB - BACKGROUND: Tourniquets are issued to deployed members of both the United States
(U.S. military and the Australian Defence Force (ADF). The ease of removing the
tourniquet from the pocket of the combat uniform may influence its time to
application. The ADF uniform uses buttons to secure the pocket, whereas the U.S.
uniform uses a hook and loop fastener system. National differences in training
may influence the time to and effectiveness of tourniquet application.
OBJECTIVES: To compare the time taken to retrieve and apply a tourniquet from the
pocket of the Australian and the U.S. combat uniform and compare the
effectiveness of tourniquet application. METHODS: Twenty participants from both
nations were randomly selected. Participants were timed on their ability to
remove a tourniquet from their pockets and then apply it effectively. RESULTS:
The U.S. personnel removed their tourniquets in shorter time (median 2.5 seconds)
than Australians (median 5.72 seconds, p < 0.0001). ADF members (mean 41.36
seconds vs. 58.87 seconds, p < 0.037) applied the tourniquet more rapidly once
removed from the pocket and trended to apply it more effectively (p = 0.1).
CONCLUSIONS: The closure system of pockets on the combat uniform might influence
the time taken to apply a tourniquet. Regular training might also reduce the time
taken to apply a tourniquet effectively.
PMID- 27483511
TI - Assessing the Dengue Diagnosis Capability Gap in the Military Health System.
AB - Dengue, one of the most widespread infectious diseases, has affected U.S.
military readiness throughout history. We explored the dengue diagnosis
capability gap by circulating a questionnaire among military end users to
determine in what capacity diagnostic test results are needed and how these
results would be used at various roles of care in the Military Health System.
Results were used to generate target product profiles for potential diagnostic
tests. We determined that at far-forward locations, diagnostic tests need to be
rugged and easy to use and are primarily needed to inform medical evacuation
decisions. In mobile or fixed hospitals, diagnostics can be less portable but
must be accurate enough to inform patient care decisions reliably. We then
evaluated the suitability of using rapid diagnostic tests and enzyme-linked
immunosorbent assays based on published performance characteristics, and we used
a model to determine positive and negative predictive values in certain simulated
deployments. In far-forward settings, a rapid diagnostic test comprising both
antigen- and antibody-based detection can fulfill the capability gap with
reasonable accuracy, whereas at higher roles of care immunoglobulin M-enzyme
linked immunosorbent assay was determined to be the most suitable option.
PMID- 27483512
TI - Supplemental Oxygen Requirements of Critically Injured Adults: An Observational
Trial.
AB - OBJECTIVES: The optimal amount of oxygen to deploy with pararescue personnel for
combat casualty care is currently unknown. The purpose of this prospective
observational trial was to determine the proportion of trauma patients requiring
supplemental oxygen, whether high or low flow rates were needed, and to evaluate
associations between injury characteristics and oxygen requirements. SUBJECTS AND
METHODS: Over 6 months, dedicated study assistants observed oxygen requirements
and delivery during the first 3 hours of emergency care for trauma patients
meeting our institution's highest level trauma team activation criteria. RESULTS:
The mean age of 204 enrolled subjects was 37 years, 79% were male, median injury
severity score was 9 (interquartile range 1-21), 58% suffered penetrating
injuries. Most (69%) were admitted; 17% went directly to the operating room, and
38% went directly to the intensive care unit from the emergency department.
136/160 nonintubated patients were managed with no or low-flow supplemental
oxygen. Penetrating injuries were less likely to require supplemental oxygen
(relative risk 0.65, 95% confidence interval 0.50-0.84). Subjects with Glasgow
Coma Scale scores <15, abdominal or chest injury, or hypotension were more likely
to require supplemental oxygen. CONCLUSION: There is significant opportunity to
reduce the need for high-flow oxygen delivery to the battlespace.
PMID- 27483513
TI - Elbow Arthrodesis as a Salvage Procedure for Combat-Related Upper Extremity
Trauma.
AB - INTRODUCTION: Upper extremity amputation is associated with significant
disability. Elbow arthrodesis (EA) is a rarely indicated salvage procedure with a
narrow set of indications. The purpose of this case series is to describe the
clinical course of those patients undergoing an EA following severe combat
related, upper extremity trauma. METHODS: 5 patients treated for combat-related
upper extremity injuries treated with an EA between 2003 and 2012 were
identified. Demographic information, injury characteristics, and treatment course
were evaluated. RESULTS: 5 male patients with a mean age of 23.8 years were
treated with an EA in relative extension following severe upper extremity trauma.
3 patients undergoing EA had concomitant bilateral above-knee amputations and 2
patients underwent fusion of their dominant arm. Successful arthrodesis was
achieved in all patients. All patients reported good pain control without
evidence of deep infection, the mean time from injury to arthrodesis was 305
days, and the mean time to arthrodesis was 714 days. The mean fusion angle among
these patients was 138 degrees . CONCLUSION: EA following severe combat-related,
upper extremity trauma is a viable treatment option. In the multiply injured
patient, arthrodesis in a position of extension may be advantageous to
accommodate transfers and mobility.
PMID- 27483514
TI - An Analysis and Summary of the Recommendations Made by the U.S. DoD 2010-2014
Recovering Warrior Task Force.
AB - In 2010, the U.S. Congress directed the Department of Defense to establish the
Recovering Warrior Task Force (RWTF) to examine the effectiveness of, and
recommend improvements to, military programs and policies for the care,
management, and transition of wounded, ill, and injured personnel. To meet its
comprehensive mandate, RWTF gathered extensive primary and secondary data that,
in combination with RWTF members' relevant experience and expertise, informed and
substantiated the recommendations that RWTF published each year. With the 2014
sunset of the Task Force, the authors, who provided research support to RWTF
throughout its tenure, sought to systematically summarize RWTF's overall
impressions regarding the shortfalls in the RW program and policy arena by
analyzing the 87 recommendations that these shortfalls motivated. Our 3-part
qualitative analysis included sorting by congressionally determined topics,
thematic analysis, and examining topic/theme convergence. We use the results of
these analyses as a framework for discussing program and policy areas that RWTF
found most in need of attention over its 4 years of operation. Among these were
continuing gaps in Department of Defense-wide policy governing the delivery of
needed resources to RWs and family caregivers, which result in disparities across
Services, Components, and locations.
PMID- 27483515
TI - Pilot Study: The Role of Predeployment Ethics Training, Professional Ethics, and
Religious Values on Naval Physicians' Ethical Decision Making.
AB - Military physicians serving overseas in cross-cultural settings face the
challenge of meeting patients' needs and adhering to their personal and
professional ethics while abiding by military obligations and duties.
Predeployment ethics training for Naval physicians continues to be received in
many forms, if received at all, and has largely not addressed their specific
roles as medical providers in the military. This study explores the perceived
effectiveness of predeployment ethics training received by Naval physicians.
Additionally, it considers the contribution of different types of ethics
training, religious values, and the professional ethics on Naval physicians'
perceived ability to effectively manage ethically challenging scenarios while on
deployment. A total of 49 Naval physicians participated in an online survey.
16.3% reported not receiving any form of ethics training before deployment. Of
those that reported receiving ethics training before deployment, 92.7% found the
ethics training received was helpful in some way while on deployment. While a
medical school course was most contributory overall to their ability to handle
ethically difficult situations while on deployment (70.7%), what most Naval
physicians felt would help them better handle these types of situations would be
a mandatory military training/military course (63.2%) or personal mentorship
(57.9%).
PMID- 27483516
TI - Psychophysiological Investigation of Combat Veterans with Subthreshold Post
traumatic Stress Disorder Symptoms.
AB - OBJECTIVE: Military service members (SMs) with subthreshold combat-related post
traumatic stress disorder (PTSD) symptoms often have clinically significant
functional impairment, even though they do not meet full PTSD criteria. We
therefore assessed the psychophysical responses of SMs, upon their return from
Afghanistan or Iraq, to a fear conditioning paradigm to better understand the
biological underpinnings of symptom severity. METHODS: Heart rate (HR), skin
conductance, electromyography startle, and respiratory rate (RR) were monitored
throughout three distinct phases of the paradigm-fear acquisition, fear
inhibition, and fear extinction-while plasma catecholamines (epinephrine,
norepinephrine, and dopamine) were measured at the end of fear inhibition.
RESULTS: Those with higher PTSD symptom severity demonstrated elevations in HR
and startle response to danger cues; elevated self-reported depression and
anxiety; impaired functional status; poor skin conductance discrimination between
danger and safety; and increases in HR and RR during fear extinction. Moreover,
an inverse relationship was seen between plasma dopamine and HR during fear
inhibition for those with high symptoms. CONCLUSION: Overall, the physiological
responses we observed in our subthreshold PTSD population parallel what has been
previously observed in full PTSD, making a case for addressing subthreshold PTSD
symptoms in combat veterans.
PMID- 27483517
TI - Poorer Physical Health is Associated With Greater Mental Health Service
Utilization in a Sample of Depressed U.S. Army National Guard Soldiers.
AB - OBJECTIVE: Operation Iraqi Freedom/Operation Enduring Freedom service members
returning from deployment suffer from high rates of depression and report low
levels of physical functioning compared to age-adjusted norms. Treatment for
depression may be limited in this group and there are few data on whether
Veterans receive medication treatment versus psychotherapy. We assessed rates of
depression, physical functioning, and treatment with either medication or
psychotherapy among recently returning service members. METHODS: Study
participants were recruited from National Guard soldiers in a Midwestern state (n
= 1,448). Logistic regression modeling was used to examine associations between
physical health and odds of receiving different types of mental health treatment
for depressed individuals (n = 299). RESULTS: 21% of soldiers reported
significant depression and 44% of depressed service members reported poor
physical health. Poorer physical health was associated with increased odds of any
treatment (odds ratio: 1.27, confidence interval: 1.1-1.45) and medication
treatment (odds ratio: 1.23, confidence interval: 1.08-1.40) but physical health
was not associated with individual psychotherapy. CONCLUSIONS: Poor physical
health is associated with increased likelihood of pharmacological but not
individual psychotherapeutic treatment. Physical health problems may increase the
need for depression care or increase contact with the medical system leading to
higher levels of pharmacological treatment. Access to psychotherapy may need to
be increased for Veterans with poor physical health.
PMID- 27483518
TI - Alcohol Use and Reasons for Drinking as Risk Factors for Suicidal Behavior in the
U.S. Army.
AB - OBJECTIVE: High levels of alcohol use and alcohol-related problems are associated
with suicidal behaviors (i.e., seriously considering and/or attempting suicide)
in military and civilian populations. Examination of reasons for drinking alcohol
may identify subgroups of soldiers who may either be at risk for suicidal
behaviors or resilient to suicidality. METHOD: We examined the associations among
reasons for drinking, level of alcohol use, and past year suicidality in 3,813
U.S. Army soldiers using the Department of Defense Survey of Health-Related
Behaviors among Active Duty Military Personnel. RESULTS: Six percent of soldiers
reported suicidal thoughts and behaviors within the past year. Those who reported
the highest level of alcohol use were more likely to have seriously considered
and/or attempted suicide. Drinking to avoid rejection/"fit in" was associated
with suicidality, even after adjusting for level of alcohol consumption, post
traumatic stress disorder, and depression. Although unadjusted analyses revealed
a relation of pleasure-seeking drinking motives to suicidality, this association
did not remain significant after controlling for covariates. CONCLUSIONS:
Drinking to avoid rejection/"fit in" is associated with suicidality above overall
alcohol consumption. Screening for this reason for drinking may be useful for
suicide prediction and prevention.
PMID- 27483519
TI - The Impact of Environment and Occupation on the Health and Safety of Active Duty
Air Force Members: Database Development and De-Identification.
AB - Preparing data for medical research can be challenging, detail oriented, and time
consuming. Transcription errors, missing or nonsensical data, and records not
applicable to the study population may hamper progress and, if unaddressed, can
lead to erroneous conclusions. In addition, study data may be housed in multiple
disparate databases and complex formats. Merging methods may be incomplete to
obtain temporally synchronized data elements. We created a comprehensive database
to explore the general hypothesis that environmental and occupational factors
influence health outcomes and risk-taking behavior among active duty Air Force
personnel. Several databases containing demographics, medical records, health
survey responses, and safety incident reports were cleaned, validated, and linked
to form a comprehensive, relational database. The final step involved removing
and transforming personally identifiable information to form a Health Insurance
Portability and Accountability Act compliant limited database. Initial data
consisted of over 62.8 million records containing 221 variables. When completed,
approximately 23.9 million clean and valid records with 214 variables remained.
With a clean, robust database, future analysis aims to identify high-risk career
fields for targeted interventions or uncover potential protective factors in low
risk career fields.
PMID- 27483520
TI - Evaluating the Impact of Hospital Efficiency on Wellness in the Military Health
System.
AB - Like all health care delivery systems, the U.S. Department of Defense Military
Health System (MHS) strives to achieve top preventative care and population
health outcomes for its members while operating at an efficient level and
containing costs. The objective of this study is to understand the overall
efficiency performance of military hospitals and investigate the relationship
between efficiency and wellness. This study uses data envelopment analysis and
stochastic frontier analysis to compare the efficiency of 128 military treatment
facilities from the Army, Navy, and Air Force during the period of 2011 to 2013.
Fixed effects panel regression is used to determine the association between the
hospital efficiency and wellness scores. The results indicate that data
envelopment analysis and stochastic frontier analysis efficiency scores are
congruent in direction. Both results indicate that the majority of the MHS
hospitals and clinics can potentially improve their productive efficiency by
managing their input resources better. When comparing the performance of the
three military branches of service, Army hospitals as a group outperformed their
Navy and Air Force counterparts; thus, best practices from the Army should be
shared across service components. The findings also suggest no statistically
significant, positive association between efficiency and wellness over time in
the MHS.
PMID- 27483521
TI - Burnout in U.S. Military Orthopaedic Residents and Staff Physicians.
AB - OBJECTIVE: The purpose of this study was to measure the prevalence of burnout
among military orthopaedic residents and staff surgeons at the U.S. Army Medical
Center. METHODS: 37 residents and 21 staff surgeons of a military orthopaedic
residency program were asked to voluntarily complete an anonymous electronic
survey. The survey consisted of two parts: first, a demographic section including
questions about relationship status, work hours, deployment history, medical
education debt, mentorship, and job satisfaction and second, the Maslach Burnout
Inventory. RESULTS: 27 residents and 11 staff completed the survey for a 67%
response rate. The rate of burnout among military orthopaedic surgeons in our
study was 7.7% (3.7% of residents and 16.7% of staff surgeons). In addition,
25.6% of surgeons (33% of residents and 8.3% of staff) were found to be at risk
of burnout. CONCLUSIONS: Future studies should focus on causal relationships
among specific aspects of the work environment and possible preventive or
protective measures. Expanding future studies to include multiple study sites
would improve the quality and generalizability of the results.
PMID- 27483522
TI - Reporting Military Sexual Trauma: A Mixed-Methods Study of Women Veterans'
Experiences Who Served From World War II to the War in Afghanistan.
AB - Since 2004, there has been increased effort to reduce military sexual trauma
(MST) in the U.S. military. Although MST covers a range of inappropriate
behaviors, the majority of research, treatment, and outreach are focused on
sexual assault and the experiences of individuals serving in Afghanistan and
Iraq. During a study on veterans' involvement in a national peace organization,
participants were asked about their military experiences. Veterans served from
World War II to current conflicts in Iraq and Afghanistan. Emerging out of the
responses were descriptions of women's experiences with MST, barriers to
reporting incidents of sexual misconduct and sexual assault, and the challenges
they faced when seeking care. Data were gathered using anonymous questionnaires
and semi-structured interviews. Out of 52 female veterans, the majority (90%) was
subjected to at least one form of MST, and 15% (8) attempted to report the
incident(s). Over half of the assailants were of a higher rank than the
survivors. The majority of veterans remained silent due to lack of options to
report, the status of perpetrators, and fear of retaliation. These data provide a
glimpse into the challenges many women veterans faced when seeking assistance
reporting incidents or obtaining health care for their MST.
PMID- 27483523
TI - Role 1 Pediatric Trauma Care on the Israeli-Syrian Border-First Year of the
Humanitarian Effort.
AB - BACKGROUND: This article summarizes the experience with Role 1 care for 135
Syrian children who received medical care during the year 2013 as part of an
ongoing humanitarian effort. METHODS: The database included demographic
information, point-of-injury assessment and outcome, and was analyzed using SPSS.
RESULTS: Trauma casualties were the majority of the group (84 cases), and mostly
male. Almost one-third of casualties arrived more than 6 hours after injury, and
time of injury was unknown in another third. The most common mechanism of injury
was shrapnel (51.2%), followed by gunshot wounds (22.6%). Gunshot wound victims
were significantly older than shrapnel and artillery victims (p < 0.01, < 0.05,
respectively). Only 14 cases (14.28%) underwent previous interventions in Syria.
Most of the casualties (44 cases, 52.4%) underwent at least one procedure during
Role 1 treatment with a high overall success rate (93.18%) that was not
correlated to Advanced Life Support provider type (physician [MD], emergency
medical technician-paramedic, or both). Mortality was low (3 cases). CONCLUSION:
The study cohort exhibits several unique features, including a delay in arrival
to medical care, paucity of prior care and information, and the specific
mechanisms of injury. Our study suggests that Advanced Life Support providers do
not differ significantly in Role 1 treatment choices and procedure success.
PMID- 27483524
TI - Parenting Stress After Deployment in Navy Active Duty Fathers.
AB - Military fathers are being deployed, and leaving their families, for greater
lengths of time and more frequently than ever before. The purpose of this study
was to examine the impact of recent deployment on parenting stress in U.S. Navy
fathers with young children. Of the 111 participants who completed the one-time
study questionnaire at a large military outpatient clinic on the Eastern
seaboard, 67.6% had returned from a ship-based deployment. Regression analyses
were performed, using the Parenting Stress Index as the outcome variable,
deployment elements (such as time away from home in the past 5 years) as
predictors, and adjusting for other factors such as post-traumatic stress
disorder (PTSD) and depression. Higher perceived threat and greater warfare
exposure were both associated with increased parenting stress (p < 0.05) in the
unadjusted model. These associations were greatly attenuated and no longer
significant after adjustment for depression. In addition, rates of positive
screens for PTSD and depression (17.1%) in this sample were higher than in other
recent studies. In summary, these data indicate that various deployment factors
are associated with increased parenting stress in Navy fathers back from
deployment within the past year; these relationships are largely explained by
depressive symptoms. Clinical implications are discussed.
PMID- 27483525
TI - Evaluation of a Technology-Based Adaptive Learning and Prevention Program for
Stress Response-A Randomized Controlled Trial.
AB - To prevent deployment-related disorders, Chaos Driven Situations Management
Retrieval System (CHARLY), a computer-aided training platform with a biofeedback
interface has been developed. It simulates critical situations photorealistic for
certain target and occupational groups. CHARLY was evaluated as a 1.5 days
predeployment training method comparing it with the routine training. The
evaluation was carried out for a matched random sample of N = 67 soldiers
deployed in Afghanistan (International Security Assistance Force). Data
collection took place before and after the prevention program and 4 to 6 weeks
after deployment, which included mental state, post-traumatic stress disorder
(PTSD) symptoms, knowledge of and attitude toward PTSD, and deployment-specific
stressors. CHARLY has been significantly superior to the control group in terms
of psychoeducation and attitude change. As to the mental state, both groups
showed a significant increase in stress after deployment with significant lower
increase in CHARLY. For PTSD-specific symptoms, CHARLY achieved a significant
superiority. The fact that PTSD-specific scales showed significant differences at
the end of deployment substantiates the validity of a specifically preventive
effect of CHARLY. The study results tentatively indicate that highly
standardized, computer-based primary prevention of mental disorders in soldiers
on deployment might be superior to other more personal and less standardized
forms of prevention.
PMID- 27483526
TI - Staying Strong With Schools: A Civilian School-Based Intervention to Promote
Resilience for Military-Connected Children.
AB - Since September 11, 2001, over 2 million U.S. service members have been deployed
to Iraq or Afghanistan, resulting in hundreds of thousands of military-connected
children (MCC) having experienced a parental deployment. Although parental
deployments have significantly burdened these children, few evidence-based
interventions designed to support their resilience to these stressors are
available. To address this gap, we developed a civilian school-based intervention
to promote resilience in MCC living in the community. Our intervention, Staying
Strong With Schools (SSWS), aims to deliver: a training to all school
professionals early in the school year to educate them about challenges for
children and families experiencing parental deployment and signs of deployment
related distress; and a year-long training for the school guidance counselor who
coordinates communication and provides psychosocial support to MCC within the
school community. We piloted SSWS in two civilian elementary schools and found
promising feasibility and acceptability.
PMID- 27483527
TI - Variable Mortality From the 1918-1919 Influenza Pandemic During Military
Training.
AB - During the 1918-1919 pandemic, influenza mortality widely varied across
populations and locations. Records of U.S. military members in mobilization camps
(n = 40), military academies, and officer training schools were examined to
document differences in influenza experiences during the fall 1918. During the
fall-winter 1918-1919, mortality percentages were higher among soldiers in U.S.
Army mobilization camps (0.34-4.3%) than among officer trainees (0-1.0%).
Susceptibility to infection and clinical expressions of 1918 pandemic influenza
varied largely based on host epidemiological characteristics rather than the
inherent virulence of the virus.
PMID- 27483528
TI - Feasibility and Patient Acceptance of Emergency Department-Based Influenza
Vaccination in a Military Medical Center.
AB - Influenza vaccination rates in the United States remain low. Many emergency
department (ED) patients may not routinely seek care elsewhere. In a survey of ED
visitors, 36.8% of unvaccinated respondents were willing to consider influenza
vaccination during their visit. Participants at high risk for influenza
complications were more likely to have been previously vaccinated, but
unvaccinated participants at high risk were not significantly more likely to
consider ED-based vaccination compared with other participants. ED-based
influenza vaccination may be an effective method to expand vaccine coverage.
PMID- 27483529
TI - Military Occupations Most Affected by Head/Sensory Injuries and the Potential Job
Impact of Those Injuries.
AB - OBJECTIVE: Identifying Department of Defense (DoD) occupations affected by
injuries to the head and sensory systems. METHODS: We explored the Defense
Medical Epidemiology Database to identify occupations with the highest incidence
of injured personnel, then ranked how frequently they occurred in a top 10 list
for each of four injury categories (head/brain, visual, auditory, vestibular)
encompassing 25 injury codes. Across all four categories, the most affected
occupations were identified, among which we chose three Army combat-related
military occupational specialties (MOSs) for detailed study. We identified skills
needed to perform these MOSs and explored whether MOS-critical deficits could be
expected following the injuries. RESULTS: Some DoD occupations are more likely to
suffer from these injuries, including Infantry, Combat Operations Control,
Artillery/Gunnery, Motor Vehicle Operator, Combat Engineering, and
Armor/Amphibious. Within these DoD occupations, we explored three Army combatant
MOSs: Infantry (11B), Cavalry Scout (19D), and Artillery (13B), confirming that
these jobs are likely to be disrupted by injuries within the four categories.
CONCLUSIONS: Head and sensory injuries disproportionately affect certain military
occupations. Relatively few injuries disrupt combat-related abilities that are
job critical (e.g., firearms operation) and job specific (e.g., Artillery gunnery
problems); these should be the focus of efforts to improve rehabilitation and RTD
outcomes.
PMID- 27483530
TI - Perceptions of ICU Diary Utility and Feasibility in a Combat ICU.
AB - Severely injured patients have difficulty recalling their intensive care unit
(ICU) experience which may contribute to emotional trauma. An ICU patient journal
contains a short summary of key events during the ICU stay, and has been shown to
improve emotional well-being. This project evaluated the feasibility and
perceptions of ICU journals in a combat ICU. A one-page survey was distributed to
ICU nursing staff at Craig Joint Theater Hospital before and after the use of ICU
journals as a process improvement initiative. 16 preimplementation and 10
postimplementation surveys were collected to determine the perception of the
utility and feasibility of ICU journals, as well as changes to nursing job
satisfaction. Overall, nurses had positive perceptions of ICU journaling; after
implementation they felt it could also benefit nurses (31% vs. 80%, p = 0.002).
ICU nurses that used journals were also more likely to feel their work makes a
difference (90%, p = 0.012) and they could connect with their patient on a
personal level (50%, p = 0.037). Primary barriers were time to journal and legal
concerns. This study demonstrates with the right guidance, ICU journals can be
incorporated into an ICU in a deployed environment and nursing staff feel they
benefit the patient, family, unit, and staff.
PMID- 27483531
TI - Descriptive Epidemiology of Musculoskeletal Injuries in the Army 101st Airborne
(Air Assault) Division.
AB - The purpose of this study was to describe the epidemiology of musculoskeletal
injuries among Soldiers of the 101st Airborne (Air Assault) Division. A total of
451 subjects (age: 27.6 +/- 6.2 years, gender: males 395/451 = 87.6%)
volunteered. Musculoskeletal injury data were extracted from subjects' medical
charts and injuries that occurred during 1 year were described. Injury frequency,
injury anatomic location and sublocation, injury cause, activity when injury
occurred, and injury type were described. Injury frequency was 29.5 injuries per
100 subjects per year. Most injures affected the lower extremity (60.2% of
injuries) and common anatomic sublocations for injuries were the ankle (17.3%)
and knee (15.0%). Frequent causes of injuries were running (13.5%) and direct
trauma (9.0%). Physical training was associated with 29.3% of the injuries. A
majority of injuries were classified as pain/spasm/ache (29.3%), without further
elucidation of pathology. Other frequent injury types were sprain (21.8%) and
strain (14.3%). The descriptive epidemiology of musculoskeletal injuries in this
population underscores the need to explore the modifiable risk factors of
potentially preventable lower extremity injuries associated with physical
training and running. There is scope for the development of an optimized and
targeted physical training program for injury prevention in this population.
PMID- 27483532
TI - Efficacy of Hemostatic Agents in Humans With Rotational Thromboelastometry: An in
vitro Study.
AB - OBJECTIVES: Hemorrhage is the leading cause of preventable death in military
conflicts. Different types of hemostatic dressings have been compared in animal
studies for their ability to control bleeding. However, the effects of hemostatic
agents in animals may be different from those in humans. The aim of this study
was to assess the efficacy of hemostatic dressings in human blood. METHODS:
Clotting time, clot formation time, alpha-angle, maximum clot firmness, and lysis
index of human blood incubated with QuikClot Gauze, Celox Gauze, QuikClot ACS+,
and standard gauze, were compared using rotational thromboelastometry (ROTEM).
Nonactivated, intrinsically activated, extrinsically activated, and fibrin-based
ROTEM were used to elucidate different mechanisms of action of those dressings.
RESULTS: QuikClot Gauze was the most efficacious hemostatic dressing, followed by
Celox Gauze and standard gauze. QuikClot ACS+ was clearly outperformed.
CONCLUSIONS: Modern hemostatic dressings such as QuikClot Gauze and Celox Gauze
should be preferred to previous generations of hemostatic dressings, such as
QuikClot ACS+. In vitro studies like ROTEM can provide valuable information about
the mechanisms of action of hemostatic dressings. A combination of different
mechanisms of action may increase the efficacy of hemostatic dressings.
PMID- 27483533
TI - The Relationship Between Enlistment Body Mass Index and the Development of
Obstructive Sleep Apnea in the U.S. Military.
AB - BACKGROUND: The incidence of obstructive sleep apnea (OSA) in the military has
risen dramatically. OSA is considered "service connected" and compensable by the
Veterans Administration. The association between body mass index (BMI) (kg/m(2))
measured at initial enlistment and development of OSA has yet to be assessed.
METHODS: Data were obtained from the Defense Medical Surveillance System, the
Armed Forces Health Surveillance Center, U.S. Department of Defense, Silver
Spring, Maryland (inclusive dates:1993-2012; release date: December 2013). A
study population of 550,000 randomly-selected active duty enlisted personnel was
followed retrospectively from January 1, 2008, through December 31, 2012, or
until diagnosis with OSA, separation from the military, or death occurred. The
main exposure of interest was BMI recorded at time of enlistment. RESULTS:
Adjusted hazard ratios for enlistment BMI were calculated using BMI of 23 to 23.9
as reference. Exponentially increasing risk for OSA was observed as BMI
increased. The heaviest individuals (BMI > 35) were at the highest risk (hazard
ratio: 3.93; 95% confidence interval [CI]: 3.35-4.62) for developing OSA.
CONCLUSION: Enlistment BMI's role in developing OSA may be valuable in designing
screening tools and preventive interventions in higher-risk groups, as well as
prompt further consideration in the realm of military enlistment policy.
PMID- 27483534
TI - Effect of a Polyp Tracking and Notification Program on Colon Adenoma Surveillance
and Compliance to Guideline Recommendations.
AB - BACKGROUND: Colorectal cancer is the third leading cause of cancer in the United
States. Surveillance colonoscopy has been shown to reduce colorectal cancer risk.
Medical institutions have implemented polyp tracking and notification programs
(registries) to ensure adequate surveillance. AIM: To assess the effectiveness of
a registry notification program initiated in January 2006 on the surveillance
colonoscopy completion rate and adherence to surveillance guidelines. METHODS:
Retrospective record review of beneficiaries with an adenomatous polyp between
2004 and 2007, with expected repeat surveillance colonoscopy between 2007 and
2012. Records were divided in 2 groups: Pre-Registry (4/04-12/05) and Registry
(1/06-6/07). Successful surveillance was defined as beneficiaries who completed
or were offered a colonoscopy within 12 months after the recommended interval.
RESULTS: A total of 853 beneficiary records were reviewed, with 88 records
excluded. Pre-Registry mean age was 60.1 years and %male gender was 63.5%,
compared to Registry mean age of 60.9 years and %male gender of 58.4%.
Significantly more beneficiaries completed or were offered colonoscopy
surveillance in the Registry group, compared to the Pre-Registry group, (85.1%
vs. 43.7%, p < 0.001). CONCLUSION: The use of a polyp tracking registry and
notification program improves adherence to current polyp surveillance guidelines.
PMID- 27483535
TI - Intimate Partner Maltreatment Recidivism in U.S. Air Force Families.
AB - Research has demonstrated that perpetrator characteristics (gender, age, and
military status) and incident characteristics (perpetrator substance use and
initial incident severity) are associated with intimate partner maltreatment
recidivism. This study assessed whether these variables were associated with
intimate partner maltreatment recidivism in U.S. Air Force families during a 16
yr period (1997-2013). During the study period, 21% of the intimate partner
maltreatment perpetrators in the U.S. Air Force committed more than one incident
of maltreatment. In terms of perpetrator characteristics, male perpetrators
reoffended more than female perpetrators, younger perpetrators reoffended more
than older perpetrators, and active duty perpetrators reoffended more than
civilians. Whether a perpetrator was enlisted or an officer was not associated
with the likelihood of recidivism. In terms of incident characteristics,
substance use (which was mainly alcohol use) during an initial maltreatment
incident was associated with recidivism, but the severity of perpetrators'
initial maltreatment incident was not. However, for perpetrators who reoffended,
the severity of their initial incident was associated with the severity of
subsequent incidents. On the basis of these findings, the need for targeted
interventions to reduce intimate partner maltreatment recidivism is discussed.
PMID- 27483536
TI - Characterization of Metacarpal Fractures in a Military Population.
AB - The purpose of this study was to investigate the incidence and type of metacarpal
(MC) fractures in a military population, and whether these fractures are related
to age, military occupational specialty, aggression, or accidental injury. A
retrospective record-based review was conducted at a single military center over
a 5-year period. Service members with index finger through small finger MC
fracture were identified. Data were collected utilizing Armed Forces Health
Longitudinal Technology Application and electronic profile (e-profile) databases.
Data collected included demographic information, mechanism of injury, nature of
injury, total number of visits, and estimated time on physical restriction. 400
patients met inclusion criteria. Males accounted for 94% of the study population,
75% of fractures were of the small finger MC, 54% of patients were between 20 and
24 years, 90% were sustained by junior enlisted personnel, and most occurred by
punching. Men aged <25 years were more likely to have intentional injuries. Total
time on limited duty profile averaged 38 days and the average medically
nondeployable profile was 26 days. MC fractures most commonly affect young, male,
junior enlisted service members and are often self-inflicted. As a result, these
injuries account for time lost at work, reduced job performance, and decreased
medical readiness.
PMID- 27483537
TI - Comparison of Penetrating Neck Injury Management in Combat Versus Civilian
Trauma: A Review of 55 Cases.
AB - The objective was to describe a case series of penetrating neck injuries (PNIs)
and compare their management in combat versus civilian trauma. METHODS: From 2012
to 2014, all soldiers and civilians referred to Percy Military Training Hospital
for PNI were analyzed. The mechanism of injury, type and site of the lesion, and
initial emergency management were noted. RESULTS: Among the 55 patients, 26 were
wounded in action, and 29 were civilians. PNIs were commonly stab wounds
resulting from an assault. Anatomical zone II, as well as the central neck
compartment, was the most affected area. The most affected organ was the larynx.
74% of patients underwent computed tomography angiography (CTA), surgical
exploration was performed for 42% of patients, and 33% of patients required
intensive care unit monitoring. The differences between the two groups in terms
of management were not statistically significant. CONCLUSIONS: The current
management is based on clinical examination and CTA and is similar between
soldiers and civilians. Surgical exploration is less commonly used than CTA,
which is a fast and accurate method to evaluate PNI for stable patients. The
classification by compartment seems more relevant than the classification by
anatomical zone, particularly in absence of medical imaging.
PMID- 27483538
TI - Pandemic, 1918.
PMID- 27483539
TI - Consider Autotransfusion in the Field.
AB - Massive hemothorax is a life-threatening condition that can present as
hemorrhagic shock, cardiogenic shock, or elements of both. It is described by the
American College of Surgeons, in the 9th Edition of Advanced Trauma Life Support,
as a rapid accumulation of more than 1,500 mL of blood or one-third or more of
the patient's blood volume. The use of autotransfusion systems has been
implemented for the treatment of hemothorax in hospital settings. The
implementation of autotransfusion has been documented in situations where an
extended period can elapse before definitive treatment can occur. This article is
the first described case where an autotransfusion system has been implemented in
a prehospital setting, at a Role 1 medical facility, for massive hemothorax in
Afghanistan.
PMID- 27483540
TI - A Patient-Controlled Analgesia Adaptor to Mitigate Postsurgical Pain for Combat
Casualties With Multiple Limb Amputation: A Case Series.
AB - The use of explosive armaments during Operation Iraqi Freedom, Operation Enduring
Freedom, and Operation New Dawn has resulted in a significant number of injured
U.S. service members. These weapons often generate substantial extremity trauma
requiring multiple surgical procedures to preserve life, limb, and restore
function. For those individuals who require multiple surgeries, the use of
patient-controlled analgesia (PCA) devices can be an effective way to achieve
adequate pain management and promote successful rehabilitation and recovery
during inpatient treatment. A subpopulation of patients are unable to
independently control a PCA device because of severe multiple limb dysfunction
and/or loss. In response to the needs of these patients, our team designed and
developed a custom adaptor to assist service members who would otherwise not be
able to use a PCA. Patient feedback of the device indicated a positive response,
improved independence, and overall satisfaction during inpatient hospitalization.
PMID- 27483541
TI - Functional Improvement Following Diastasis Rectus Abdominus Repair in an Active
Duty Navy Female.
AB - Return to physical activity following childbirth can be a difficult process
complicated by structural changes during pregnancy. A common problem is the
development of a diastasis of the rectus abdominus (DRA), defined as a horizontal
separation of the abdominus muscles at the linea alba. Recent data indicate that
the greater the distance of separation of the muscle, the worse the functional
ability. We describe a 24-year-old active duty U.S. Navy female G1P2 with a
diagnosis of DRA. At 2 months postpartum, she was referred to physical therapy
because of back pain and inability to meet baseline activities of daily living.
After 4 months of physical therapy, she was unable to complete curl ups as
required by U.S. Navy physical fitness standards. Abdominoplasty with imbrication
of the abdominal wall diastasis was performed followed by additional physical
therapy, after which she returned to baseline functioning. The restoration of
functional ability postoperatively suggests there is a therapeutic indication for
surgical correction of DRA. In high-functioning military patients with DRA who
fail to return to baseline level of activity following a trial of physical
therapy, surgical intervention should be considered to obtain the optimal
functional ability.
PMID- 27483542
TI - Chronic Left Lower Lobe Pulmonary Infiltrates During Military Deployment.
AB - Deployment to Southwest Asia is associated with increased airborne hazards such
as geologic dusts, burn pit smoke, vehicle exhaust, or air pollution. There are
numerous ongoing studies to evaluate the potential effects of inhaled particulate
matter on reported increases in acute and chronic respiratory symptoms. Providers
need to be aware of potential causes of pulmonary disease such as acute
eosinophilic pneumonia, asthma, and vocal cord dysfunction that have been
associated with deployment. Other pulmonary disorders such as interstitial lung
disease are infrequently reported. Not all deployment-related respiratory
complaints may result from deployment airborne hazards and a broad differential
should be considered. We present the case of a military member with a prolonged
deployment found to have lobar infiltrates secondary to pulmonary vein stenosis
from treatment for atrial fibrillation.
PMID- 27483543
TI - Occult Pneumomediastinum in the Deployed Setting: Evaluation and Management.
AB - Pneumomediastinum can occur after both blunt and penetrating trauma. The greatest
concern involving this finding in a trauma patient is an aerodigestive tract
injury. Prompt evaluation, identification, and management of these injuries are
extremely important. This case describes a soldier who was involved in an
improvised explosive device blast with no evidence of cavity penetration. During
the routine evaluation of his head and neck an occult pneumomediastinum was
identified. The patient was asymptomatic and was further evaluated with computed
tomography because of the absence of endoscopy and bronchoscopy in theatre. The
imaging showed no evidence of esophageal or tracheobronchial injury. The patient
was observed and when noted to be stable was transferred to the local Role 3
hospital for management of his other injuries.
PMID- 27483544
TI - Penetrating Orbital Injury From a Needlefish.
AB - Orbital penetrating injuries are an unfortunately common occurrence; however,
those from marine animals are rare. Injuries from marine animals can be quite
profound and there are no known reports of complete visual recovery after an
orbital penetrating injury. Complications range from secondary infection to a
carotid-cavernous fistula, which can complicate the management of these patients.
We report a case of penetrating orbital injury from a needlefish with complete
return of visual function after surgical removal of foreign debris and an
extended course of antibiotics.
PMID- 27483545
TI - Cirrhosis in an Active Duty Soldier With Concomitant Isolated Polycystic Disease
and H63D Homozygosity.
AB - We report the case of a 45-year-old male soldier who was evaluated for a rapidly
expanding hepatic mass following cholecystectomy and was eventually found to have
isolated polycystic liver disease and express HFE H63D homozygosity. Both H63D
homozygosity and isolated polycystic liver disease are only rarely associated
with clinical cirrhosis. This is the first reported case of their concomitant
presentation.
PMID- 27483546
TI - Specialists seek to enhance trust in their credentials.
PMID- 27483547
TI - Need, fairness debated in nonprofit roles.
PMID- 27483548
TI - Technicians pushing for new name: veterinary nurse.
PMID- 27483549
TI - Practicing caution with prescription of antimicrobials.
PMID- 27483550
TI - The authors respond.
PMID- 27483551
TI - Fond memories of veterinary mentors.
PMID- 27483552
TI - Treatment of immune-mediated polyarthritis in dogs.
PMID- 27483554
TI - Findings of Research Misconduct.
PMID- 27483553
TI - [Forms of intra-erythrocytes asexual multiplication of P. falciparium. Production
of monoclonal antibodies].
PMID- 27483555
TI - Women's Health Coverage Since the ACA: Improvements for Most, But Insurer
Exclusions Put Many at Risk.
AB - Issue: Since enactment of the Affordable Care Act (ACA), many more women have
health insurance than before the law, in part because it prohibits insurer
practices that discriminate against women. However, gaps in women's health
coverage persist. Insurers often exclude health services that women are likely to
need, leaving women vulnerable to higher costs and denied claims that threaten
their economic security and physical health. Goal: To uncover the types and
incidence of insurer exclusions that may disproportionately affect women's
coverage. Method: The authors examined qualified health plans from 109 insurers
across 16 states for 2014, 2015, or both years. Key findings and conclusions: Six
types of services are frequently excluded from insurance coverage: treatment of
conditions resulting from noncovered services, maintenance therapy, genetic
testing, fetal reduction surgery, treatment of self-inflicted conditions, and
preventive services not covered by law. Policy change recommendations include
prohibiting variations within states' "essential health benefits" benchmark plans
and requiring transparency and simplified language in plan documents.
PMID- 27483556
TI - Rapid separation of the major phospholipid classes on a single aminopropyl
cartridge.
AB - A rapid method for the separation of the individual phospholipid classes
phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS)
and phosphatidylinositol (PI) by a single solid-phase extraction was developed.
PC, PE, PS and PI were sequentially eluted from aminopropyl bonded silica with
acetonitrile/n-propanol (2?1, vol/vol), methanol, isopropanol/methanolic HCl
(4?1, vol/vol) and methanol/methanolic HCl (9?1, vol/vol). Standard recoveries
were over 95% for PC and PE and over 85% for PS and PI with undistorted fatty
acid composition. The separation of complex lipid mixtures on aminopropyl
minicolumns can be refined to the level of individual phospholipid classes.
PMID- 27483557
TI - General ward and pneumonia size as predictors of noninvasive ventilation failure.
AB - INTRODUCTION: Shortage of intensive care beds has led to more frequent use of
noninvasive ventilation (NIV) outside respiratory units, and data on NIV efficacy
and safety on general wards is lacking. OBJECTIVE: The aim was to identify
potential predictors for NIV failure. METHODS: This was a retrospective analysis
of patients treated with NIV at the Institute for Pulmonary Diseases of Vojvodina
from 2009 to 2013. Demographics, blood gases, chest radiographs, setting, and
outcomes were analyzed to identify predictors of NIV failure. RESULTS: A total of
138 patients (65% men, mean age 66 +/- 11 years) were treated with NIV.
Indications for NIV were acute exacerbation of chronic obstructive pulmonary
disease (85%) and cardiogenic pulmonary edema (7%), as well as respiratory
insufficiency related to obesity and central hypoventilation (5%) and
neuromuscular disease (3%). Rate of NIV failure was 34.8%. In 86 patients NIV was
applied in the High Dependency Unit (HDU), while 52 received NIV on the general
ward. Baseline characteristics in terms of gender, arterial blood gases, and the
extent of consolidation on chest radiographs were similar. Patients treated in
HDU were younger (64.4 +/- 1.2 vs. 69.4 +/- 1.5 years, p < 0.001). NIV on the
general ward compared to HDU had higher rates of NIV failure (28/52 vs. 20/86, p
< 0.001). Presence of consolidation involving two or more quadrants on chest
radiograph (55% vs. 29%, p < 0.001) was associated with NIV failure. When
adjusted for age and the extent of consolidation on chest radiograph, NIV failure
was still less likely in patients treated in HDU (OR 0.23, 95% Cl 0.10-0.50).
CONCLUSION: Patients with consolidation on chest X-ray and patients treated with
NIV outside of dedicated respiratory units are at a higher risk for NIV failure.
PMID- 27483558
TI - Comparison of the efficiency of clomiphene citrate and letrozole in combination
with metformin in moderately obese clomiphene citrate-resistant polycystic
ovarian syndrome patients.
AB - INTRODUCTION: Polycystic ovary syndrome is the most common endocrinopathy in
women of reproductive-age. Therapy for those who want to get pregnant involves
ovulation induction using clomiphene citrate, metformin, letrozole and
gonadotropins. OBJECTIVE: The aim of the study was to compare the efficacy of
combinations of clomiphene citrate-metformin and letrozole-metformin in obese
patients who are resistant to clomiphene citrate alone. METHODS: The
investigation was conducted as a retrospective study involving 60 moderately
obese patients with polycystic ovary syndrome. Thirty-one of them received the
clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was
carried out for the procedures of intrauterine insemination (IUI). RESULTS: The
age of patients, duration of infertility, and body mass index in both groups were
similar. There was statistically significant difference in the thickness of the
endometrium in favor of the group having the letrozole-metformin therapy (8.9 +/-
1.7 mm) compared with the group receiving the clomiphene citrate-metformin
treatment (6.3 +/- 1.3 mm). The number of follicles was not statistically
significantly different. Pregnancy rate in the first cycle of IUI in the
clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also
was not statistically different. After the third IUI cycle, the pregnancy rate
was significantly higher in the letrozole group (20.6%), while in the clomiphene
citrate group it was (9.6%). CONCLUSION: This retrospective study demonstrated
the advantages of the use of letrozole over clomiphene citrate in combination
with metformin in moderately obese patients with polycystic ovary syndrome who
are resistant to stimulation with clomiphene citrate alone.
PMID- 27483559
TI - The effect of anterior cruciate ligament reconstruction on hamstring and
quadriceps muscle function outcome ratios in male athletes.
AB - INTRODUCTION: Maximal strength ratios such as the limb symmetry index (LSI) and
hamstring-to-quadriceps ratio (HQ) may be considered the main outcome measures in
the monitoring of recovery after anterior cruciate ligament (ACL) reconstruction.
Although explosive strength is much more important than maximal strength, it is
generally disregarded in the follow-up of muscle function recovery. OBJECTIVE:
The purpose of this study was to compare ratios between maximal (Fmax) and
explosive strength (rate of force development--RFD) in individuals with ACL
reconstruction. METHODS: Fifteen male athletes were enrolled and had maximum
voluntary isometric quadriceps and hamstring contractions tested (4.0 +/- 0.1
months post reconstruction). In addition to Fmax RFD was estimated (RFDmax, as
well as RFD at 50, 100, and 200 ms from onset of contraction) and LSI and HQ
ratios were calculated. RESULTS: The involved leg demonstrated significant
hamstring and quadriceps deficits compared to uninvolved leg (p < 0.01). Deficits
were particularly significant in the involved quadriceps, causing higher HQ
ratios (average 0.63), compared to the uninvolved leg (0.44). LSI was
significantly lower for RFD variables (average 55%) than for Fmax (66%).
CONCLUSION: The assessment of RFD may be considered an objective recovery
parameter for one's readiness to return to sports and should be an integral part
of standard follow-up protocol for athletes after ACL reconstruction. Moreover,
the combination of indices derived from maximal and explosive strength may
provide better insight in muscle strength balance, as well as a clear picture of
functional implications.
PMID- 27483560
TI - Ability to solve riddles in patients with speech and language impairments after
stroke.
AB - INTRODUCTION: Successful riddle solving requires recognition of the meaning of
words, attention, concentration, memory, connectivity and analysis of riddle
content, and sufficiently developed associative thinking. OBJECTIVE: The aim of
the study was to determine the ability to solve riddles in stroke patients who do
or do not have speech and language disorders (SLDs), to determine the presence of
SLDs in relation to the lesion localization, as well as to define the
relationship between riddle-solving and functional impairment of a body side.
METHODS: The sample consisted of 88 patients. The data used included age, sex,
educational level, time of stroke onset, presence of an SLD, lesion localization,
and functional damage of the body side. The patients were presented with a task
of solving 10 riddles. RESULTS: A significant SLD was present in 38.60% of the
patients. Brain lesions were found distributed at 46 different brain sites.
Patients with different lesion localization had different success in solving
riddles. Patients with perisylvian cortex brain lesions, or patients with
Wernicke and global aphasia, had the poorest results. The group with SLDs had an
average success of solved riddles of 26.76% (p = 0.000). The group with right
sided functional impairments had average success of 37.14%, and the group with
functional impairments of the left side of the body 56.88% (p = 0.002).
CONCLUSION: Most patients with SLDs had a low ability of solving riddles. Most of
the patients with left brain lesions and perisylvian cortex damage demonstrated
lower ability in solving riddles in relation to patients with right hemisphere
lesions.
PMID- 27483561
TI - Determinants of job satisfaction of healthcare professionals in public hospitals
in Belgrade, Serbia--Cross-sectional analysis.
AB - INTRODUCTION: The quality of health care significantly depends on the
satisfaction of the employees. OBJECTIVE: The objective of this study was to
establish the level of professional satisfaction of healthcare professionals in
state hospitals in Belgrade, Serbia, and to determine and to rank the factors
which impact on their satisfaction or dissatisfaction. METHOD: Professional
satisfaction survey was designed and conducted as a cross-sectional study in
2008. Completed questionnaires were returned by 6,595 healthcare professionals
from Belgrade's hospitals. Statistical analysis was performed using the Student's
t-test, chi2 test and ANOVA. Factor analysis was applied in order to define
determinants of professional satisfaction, i.e. dissatisfaction. RESULTS: This
study showed that the degree of professional satisfaction of Serbian healthcare
professionals was low. The main causes of professionals'dissatisfaction were
wages, equipment, the possibility of continuous medical education/training and
the opportunities for professional development. Healthcare professionals with
university education were more satisfied with all the individual aspects of job
satisfaction than those with secondary school and college education. CONCLUSION:
There were significantly more healthcare professionals satisfied with their job
among males, older than 60 years, in the age group 50-59 years, with managerial
function, and with 30 or more years of service. Development strategy of human
resources in the Serbian health care system would significantly improve the
professional satisfaction and quality of the provided health care.
PMID- 27483562
TI - Outcome of orthograde endodontic retreatment--A two-year follow-up.
AB - INTRODUCTION: Endodontic retreatment is a complex intervention that requires
detailed analysis of possible reasons for failure, and flawless practical
execution of the procedure. OBJECTIVE: The aim of the study was to assess the
outcome of endodontic retreatment based on clinical and radiographic criteria
after a two-year observation period. METHODS: Clinical study included 49 teeth
indicated for endodontic retreatment based on periapical index (PAI). All teeth
were divided into two groups. Group I comprised teeth without any periapical
lesion (PAI score of 1 and 2) while Group II consisted of teeth with visible
periapical radiolucency (PAI score of 3, 4, and 5). Endodontic retreatment was
completed in two visits with inter-appointment medication of 2% chlorhexidine and
calcium hydroxide for two weeks. Outcome of endodontic retreatment was evaluated
12-24 months after final obturation. RESULTS: Endodontic retreatment was
successful in 93.3% in Group I after 24 months. In Group II, successful treatment
and complete healing was found in 52.9% of teeth, whereas 14.7% of teeth showed
only partial healing. However, clinical symptomatology was not present in any of
the cases. Considering the absence of clinical signs and subjective symptoms,
retreatment was successful in 67.6% of cases where chronic periapical
inflammation was present. CONCLUSION: Endodontic retreatment was successful in
high percentage in teeth with and without periapical lesions.
PMID- 27483563
TI - Posture in dentists: Sitting vs. standing positions during dentistry work--An EMG
study.
AB - INTRODUCTION: Adequate working posture is important for overall health.
Inappropriate posture may increase fatigue, decrease efficiency, and eventually
lead to injuries. OBJECTIVE: The purpose was to examine posture positions used
during dentistry work. METHODS: In order to quantify different posture positions,
we recorded muscle activity and positions of body segments. The position
(inclination) data of the back was used to assess two postures: sitting and
standing during standard dental interventions. RESULTS: During standard
interventions, whether sitting or standing, a tilt of less than 20 degrees was
most prevalent in the forward and lateral flexion directions. Amplitude of
electromyography signals corresponding to the level of muscle activity were
higher in sitting compared with the electromyography in standing position for all
muscle groups on the left and right side of the body. Significant difference
between muscle activity in two working postures was evident in splenius capitis
muscle on the left (p = 0.032), on the right side of the body (p = 0.049) and in
muscle activity of mastoid muscle on the left side (p = 0.029). CONCLUSION: These
findings show that risk for increased fatigue and possible injures can be reduced
by combining the sitting and standing occupational postures.
PMID- 27483564
TI - Analysis of load distribution in tooth-implant supported fixed partial dentures
by the use of resilient abutment.
AB - INTRODUCTION: Differences between the tooth and implant response to load can lead
to many biological and technical implications in the conditions of occlusal
forces. OBJECTIVE: The objective of this study was to analyze load distribution
in tooth/implant-supported fixed partial dentures with the use of resilient TSA
(Titan Shock Absorber, BoneCare GmbH, Augsburg, Germany) abutment and
conventional non-resilient abutment using finite element method. METHODS: This
study presents two basic 3D models. For one model a standard non-resilient
abutment is used, and on the implant of the second model a resilient TSA abutment
is applied. The virtual model contains drawn contours of tooth, mucous membranes,
implant, cortical bones and spongiosa, abutment and suprastructure. The
experiment used 500 N of vertical force, applied in three different cases of
axial load. Calculations of von Mises equivalent stresses of the tooth root and
periodontium, implants and peri-implant tissue were made. RESULTS: For the model
to which a non-resilient abutment is applied, maximum stress values in all three
cases are observed in the cortical part of the bone (maximum stress value of 49.7
MPa). Measurements of stress and deformation in the bone tissue in the model with
application of the resilientTSA abutment demonstrated similar distribution;
however, these values are many times lower than in the model with non-resilient
TSA abutment (maximum stress value of 28.9 MPa). CONCLUSION: Application of the
resilient TSA abutment results in more equal distribution of stress and
deformations in the bone tissue under vertical forces. These values are many
times lower than in the model with the non-resilient abutment.
PMID- 27483565
TI - Surgical treatment of intramural hematoma of the ascending aorta.
AB - INTRODUCTION: Intramural hematoma of the aorta presents potentially fatal
condition developing as a result of a vasa vasorum rupture. It is a major risk
factor for developing a frank aortic dissection. CASE OUTLINE: A 65-year-old
woman was admitted to our clinic for the second time, after her symptoms of chest
pain and vertigo (with no electrocardiographic signs of myocardial infarction)
hadn't disappeared after several months of medicament treatment (indicated in the
first hospitalization). Computed tomography arteriography of the aorta showed no
sign of acute aortic dissection, but revealed a contrast depo in the aortic wall
of 8 x 14 mm dimensions, with no extravasation of contrast. Also, massive
pericardial effusion was observed (10-30 mm in thickness). Transesophageal
echocardiography confirmed these findings completely. The patient underwent
surgery, in which plaque exulceration was detected on the convex side of the
ascending aorta, 3 cm above the aortic valve, 1 cm in diameter, with no signs of
intimal tear. A resection of the ascending aorta was performed, and the aorta was
reconstructed with a 30 mm Dacron tube graft. The patient was discharged on the
14th postoperative day with satisfactory results. CONCLUSION: Intramural hematoma
is not a common event, but it is potentially a fatal one. Open surgery in
patients with an intramural hematoma is an effective treatment strategy, although
percutaneous endovascular treatment options are being described.
PMID- 27483566
TI - Challenges in interpretation of thyroid hormone test results.
AB - INTRODUCTION: In interpreting thyroid hormones results it is preferable to think
of interference and changes in concentration of their carrier proteins. OUTLINE
OF CASES: We present two patients with discrepancy between the results of thyroid
function tests and clinical status. The first case presents a 62-year-old patient
with a nodular goiter and Hashimoto thyroiditis. Thyroid function test showed low
thyroid-stimulating hormone (TSH) and normal to low fT4. By determining thyroid
status (TSH, T4, fT4,T3, fT3) in two laboratories, basal and after dilution, as
well as thyroxine-binding globulin (TBG), it was concluded that the thyroid
hormone levels were normal. The results were influenced by heterophile antibodies
leading to a false lower TSH level and suspected secondary hypothyroidism.The
second case, a 40-year-old patient, was examined and followed because of the
variable size thyroid nodule and initially borderline elevated TSH, after which
thyroid status showed low level of total thyroid hormones and normal TSH. Based
on additional analysis it was concluded that low T4 and T3 were a result of low
TBG. It is a hereditary genetic disorder with no clinical significance.
CONCLUSION: Erroneous diagnosis of thyroid disorders and potentially harmful
treatment could be avoided by proving the interference or TBG deficiency whenever
there is a discrepancy between the thyroid function results and the clinical
picture.
PMID- 27483567
TI - Severe neonatal subgaleal hemorrhage as the first presentation of hemophilia A.
AB - INTRODUCTION: Subgaleal hemorrhage is a rare but potentially fatal birth trauma.
It is caused by rupture of the emissary veins (connections between the dural
sinuses and scalp veins), followed by the accumulation of blood between the
epicranial aponeurosis and the periosteum. Usually, it is associated with
instrumental delivery (vacuum extraction, forceps delivery), but it may also
occur spontaneously, suggesting the possibility of congenital bleeding disorder.
CASE OUTLINE: A full term male neonate was born at 40 weeks gestation by
spontaneous vaginal delivery, with birth weight of 3,700 g. The Apgar scores were
9 and 10 at 1 and 5 minutes, respectively. At the age of 23 hours, the baby
became pale and lethargic. Large fluctuant swelling on his head was noted. He
developed severe anemia and hypovolemia as a result of massive subgaleal
hemorrhage. After successful treatment, the baby fully recovered. Follow-up and
further evaluation revealed hemophilia A as a result of a de novo mutation.
CONCLUSION: This case illustrates that subgaleal hemorrhage may be the first
presentation of hemophilia A. Infants without obvious risk factors for developing
subgaleal hemorrhage should be evaluated for congenital bleeding disorder.
Successful outcome in affected infants requires early diagnosis, careful
monitoring and prompt treatment.
PMID- 27483568
TI - Hypercalcemia with multiple osteolytic lesions and increased circulating tumor
necrosis factor in an adult patient with B-cell acute lymphoblastic leukemia.
AB - INTRODUCTION: Acute lymphoblastic leukemia (ALL) is very rarely presented with
diffuse osteolytic lesions and hypercalcemia. CASE OUTLINE: We report a 28-year
old male with the B-cell ALL who presented with extensive osteolytic lesions,
bone pain, hepatosplenomegaly, and pancytopenia without circulating blasts in
peripheral blood. An increased serum level of tumor necrosis factor (TNF-alpha)
was registered while the levels of IL-1alpha and IL-1beta were normal. The
patient failed to achieve remission on two induction regimens but achieved one
after the successful allogeneic stem cell transplantation, which lasted for six
months, after which he developed a relapse and died. CONCLUSION: The presented
case may serve as a clinical demonstration of possible involvement of TNF-alpha
as a pathogenic factor in the evolution of osteolytic lesions that are
occasionally observed in patients with ALL. This might have relevance in the
management of such patients as chemotherapy alone may not represent the
beneficial option in this clinical context.
PMID- 27483569
TI - Laparoscopic gastric wedge resection as the method of choice in the treatment of
gastrointestinal stromal tumors--A case report.
AB - INTRODUCTION: The gastrointestinal stromal tumors (GIST) are the most frequent
mesenchymal tumors of the gastrointestinal tract. The surgery of resectable
gastric GIST is the primary therapy for these tumors, but the decision regarding
the surgical radicality of the procedures is still a point of discussion among
surgeons and oncologists. CASE OUTLINE: A 74-year-old patient was admitted to
hospital with signs of bleeding from the upper parts of the gastrointestinal
tract. Urgent gastroscopy was performed and a subepithelial gastric lesion with
bleeding ulceration was noted in the region of the fornix. A computed tomography
scan of the abdomen showed a tumor in the fornix region with the dimensions of 48
x 32 mm, which was growing mostly intraluminally. After an adequate preoperative
preparation the patient underwent a laparoscopic wedge resection of gastric
fornix with intramural tumor lesion. The histopathological analysis of the
specimen showed a well differentiated GIST (histological grade Gi), of the
spindle cell type. Based on the immunohistochemical analysis of thespecimen it
was concluded that the patient was in the IA stage of the disease with a low risk
of malignant progression. In the population of patients with GIST, this is the
most common group (43%), with low malignant potential, and relapses present in
only 3.6% of cases.The patient started with oral food intake on the first
postoperative day, the first bowel movement occurred 36 hours after surgery, and
the patient was released from hospital on the fourth postoperative day.
CONCLUSION: Based on the aforementioned, we consider that the laparoscopic
gastric wedge resection is a safe and efficient surgical procedure. This is
primary therapy for most common group of patients with resectable gastric GIST.
PMID- 27483570
TI - Granulomatous interstitial nephritis associated with influenza A: H1N1 infection-
A case report.
AB - INTRODUCTION: The causes of acute tubulointerstitial nephritis can be grouped
into four broad categories: medications, infections, immunologic diseases, or
idiopathic processes. Here we report a 17-year-old female who developed acute
kidney injury (AKI) due to granulomatous interstitial nephritis (GIN) associated
with influenza A: H1N1 infection. CASE OUTLINE: The illness presented after two
weeks of respiratory tract infection, skin rash and hypermenorrhea. On admission
the patient was febrile, with bilateral pedal edema, macular skin rash, and
auscultatory finding that suggested pneumonia. Laboratory investigations showed
normocytic anemia, azotemia, hematuria and proteinuria. Renal ultrasound was
normal. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, lupus
anticoagulant, antiphospholipid antibodies were negative with normal complement.
Urine cultures including analysis for Mycobacterium tuberculosis were negative.
The diagnosis of influenza A: H1N1 infection was made by positive serology. A
kidney biopsy showed interstitial nephritis with peritubular granulomas.
Glomeruli were normal. Staining for immunoglobulins A, M, G, and F was negative.
The girl was treated with oseltamivir phosphate (Tamiflu; Genentech, Inc., South
San Francisco, CA, USA) for five days, as well as with tapered prednisone after a
starting dose of 2 mg/kg. The treatment resulted in a complete remission during
two years of follow-up. CONCLUSION: We present a severe but reversible case of
GIN and AKI associated with influenza A: H1N1 infection. Although a causal effect
cannot be confirmed, this case suggests that influenza A: H1N1 should be
considered in the differential diagnosis of GIN manifested with AKI in children.
PMID- 27483571
TI - A massive bleeding from a gastrointestinal stromal tumor of a Meckel's
diverticulum.
AB - INTRODUCTION: Meckel's diverticulum is the most common congenital anomaly of the
gastro intestinal tract, present in about 2% of population. CASE OUTLINE: The
article presents the case of a 44-year-old otherwise healthy man with anemia, who
was diagnosed lower gastrointestinal bleeding. An abdominal CT scan revealed a
clearly demarcated solid tumor in hypogastric region, measuring 65 x 45 mm. A
laparotomy through lower midline incision was performed. A surgical resection of
a lesion of a Meckel's diverticulum was carried out and a final diagnosis of
gastrointestinal stromal tumor was made.The patient made an uneventful recovery.
CONCLUSION: The preoperative diagnosis of a complicated Meckel's diverticulum may
be challenging. CT is usually an adequate method to diagnose tumors arising from
Meckel's diverticulum.
PMID- 27483572
TI - Carbon nanomaterials: Biologically active fullerene derivatives.
AB - Since their discovery, fullerenes, carbon nanotubes, and graphene attract
significant attention of researches in various scientific fields including
biomedicine. Nano-scale size and a possibility for diverse surface modifications
allow carbon nanoallotropes to become an indispensable nanostructured material in
nanotechnologies, including nanomedicine. Manipulation of surface chemistry has
created diverse populations of water-soluble derivatives of fullerenes, which
exhibit different behaviors. Both non-derivatized and derivatized fullerenes show
various biological activities. Cellular processes that underline their toxicity
are oxidative, genotoxic, and cytotoxic responses.The antioxidant/cytoprotective
properties of fullerenes and derivatives have been considered in the prevention
of organ oxidative damage and treatment. The same unique physiochemical
properties of nanomaterials may also be associated with potential health hazards.
Non-biodegradability and toxicity of carbon nanoparticles still remain a great
concern in the area of biomedical application. In this review, we report on basic
physical and chemical properties of carbon nano-clusters--fullerenes, nanotubes,
and grapheme--their specificities, activities, and potential application in
biological systems. Special emphasis is given to our most important results
obtained in vitro and in vivo using polyhydroxylated fullerene derivative
C60(OH)24.
PMID- 27483573
TI - [Acute renal failure in patients with tumour lysis sindrome].
AB - 'Hematologic malignancies (leukemia, lymphoma, multiple myeloma, et al.), as well
as solid tumours (renal, liver, lung, ovarian, etc.), can lead to acute or
chronic renal failure.The most common clinical manifestation is acute renal
failure within the tumour lysis syndrome (TLS). It is characterized by specific
laboratory and clinical criteria in order to prove that kidney disorders result
from cytolysis of tumour cells after chemotherapy regimen given, although on
significantly fewer occasions it is likely to occur spontaneously or after
radiotherapy. Essentially, failure is the disorder of functionally conserved
kidney or of kidney with varying degrees of renal insufficiency, which render the
kidney impaired and unable to effectively eliminate the end products of massive
cytolysis and to correct the resulting disorders: hyperuricemia, hyperkalemia,
hypocalcaemia, hyperphosphatemia, and others. The risk of TLS depends on tumour
size, proliferative potential of malignant cells, renal function and the presence
of accompanying diseases and disorders. Hydration providing adequate diuresis and
administration of urinary suppressants (allopurinol, febuxostat) significantly
reduce the risk of developing TLS. If prevention of renal impairment isn't
possible, the treatment should be supplemented with hemodynamic monitoring and
pharmacological support, with the possible application of recombinant urate
oxidase enzyme (rasburicase). Depending on the severity of azotemia and
hydroelectrolytic disorders, application of some of the methods of renal
replacement therapy may be considered.
PMID- 27483575
TI - Editorial.
PMID- 27483574
TI - [Treatment by bloodletting in the past and present].
AB - INTRODUCTION: Therapeutic bloodletting has been practiced at least 3000 years as
one of the most frequent methods of treatment in general, whose value was not
questioned until the 19th century, when it was gradually abandoned in Western
medicine, while it is still practiced in Arabic and traditional Chinese medicine.
CONTENT: In modern medicine bloodletting is practiced for very few indications.
Its concept was modeled on the process of menstrual bleeding, for which it was
believed to"purge women of bad humours. "Thus, bloodletting was based more on the
belief that it helps in the reestablishment of proper balance of body "humours"
than on the opinion that it serves to remove excessive amount of blood as well as
to remove toxic "pneumas" that accumulate in human body. It was indicated for
almost all known diseases, even in the presence of severe anemia. Bloodletting
was carried out by scarification with cupping, by phlebotomies (venesections),
rarely by arteriotomies, using specific instruments called lancets, as well as
leeches. In different periods of history bloodletting was practiced by priests,
doctors, barbers, and even by amateurs. In most cases, between one half of liter
and two liters of blood used to be removed. Bloodletting was harmful to vast
majority of patients and in some of them it is believed that it was either fatal
or that it strongly contributed to such outcome. In the 20th century in the
"Western"medicine bloodletting was still practiced in the treatment of
hypertension and in severe cardiac insufficiency and pulmonary edema, but these
indications were later abandoned. CONCLUSION: Bloodletting is still indicated for
a few indications such as polycythemia, haemochromatosis, and porphyria cutanea
tarda, while leeches are still used in plastic surgery, replantation and other
reconstructive surgery, and very rarely for other specific indications.
PMID- 27483576
TI - [Today's importance of ultrasound in ENT].
AB - Since ultrasound has been established for diagnosis in ENT several new techniques
have been introduced. But also ultrasonography has technically developed and thus
has earned even more importance and indications. This was to be shown by this
paper as well as the advantages and pitfalls. Ultrasound is quite useful in
inflammatory, infectious and tumor pathology in order to make a better diagnosis
or staging and to help the surgeon for punture or incision of a pathologic lesion
(cytology, bacteriology, drainage). Especially in ENT oncology and post-treatment
follow up ultrasound is a very precious technique. Ultrasound can be realized by
the ENT specialist himself anywhere and at any time. It is a non aggressive, non
invasive technique and its cost is relatively low. Unfortunately by itself it is
not very performant to distinguish benign and malignant lesions. But its
specificity can be considerably enhanced by combinating it with cytology (UGFNAB,
ultrasound guided fine needle aspiration biopsy). Another important field of
ultrasound is the examination of salivary glands.
PMID- 27483577
TI - Value of the preservation of an osseous mandibular rim with a fibula free flap
reconstruction.
AB - BACKGROUND: Reconstruction of the mandible with microvascularized fibula
transplants is actually a well-established procedure, yet the major component is
the limited diameter of the diaphysis that can induce oral rehabilitation's
failure, especially in dentate patients. In this paper, we report our surgical
procedure allowing preservation of the mandibular height. The primary objective
was to assess aesthetic and functional improvements of preservation of an osseous
mandibular rim with a fibula free flap reconstruction. PATIENTS AND METHODS: Five
patients (all males, mean age of 60 years) were treated with this method.
Aetiologies were tumour in 3 cases, and osteoradionecrosis in the two others
cases. We described all step of our surgical procedure and the functional,
aesthetic and carcinologic results were evaluated. The follow up varies from 6 to
30 months. RESULTS: One patient died at 12 days from unrelated affection. For the
other patients, both the aesthetics and functional outcomes were better than in
case of mandibular interruption surgery. In fact, the mandibular contour of the
mandibule was preserved and the height of mandible was restored. One patient is
in progress of dental rehabilitation with osseous implants. Carcinologically, no
local recurrence was observed. CONCLUSION: This technique is reliable and enables
to optimize oral rehabilitation with endosteal implants. Nevertheless, we
consider that the 3D scanner is essential before the intervention to evaluate the
osseous reach. Moreover, if necessarily the procedure can be modified
intraoperatively.
PMID- 27483578
TI - Cholesteatoma presenting as a late complication of cochlear implant surgery: Case
report and literature review.
AB - A male patient with post lingual hearing loss was implanted at 16 years of age
with a Nucleus cochlear implant (Cochlear) in his left ear. Twenty two years
later, he developed a cholesteatoma in relation to the mastoid portion of the
facial nerve and in contact with the electrodes array. The cholesteatoma was
removed and the ear canal reconstructed. There was no post-operative facial palsy
and the cochlear implant was preserved. Although cholesteatoma is a rare
complication of the cochlear implant surgery, it still can occur and can be a
source of potential damage to the implant. The origin of this late-presenting
complication could be excessive bone drilling associated with the pressure caused
by the loop of the electrodes array on the posterior canal wall. Implanted
patients must have a close and particular long-term follow-up, especially when a
surgical breach of the canal wall or a tear of the tympanic membrane have
occurred during surgery, as well as in those patients in whom excessive thinning
out of the posterior meatal wall was done.
PMID- 27483579
TI - [Sarcoidosis of the thyroid: A case report].
AB - OBJECTIVE: To present a case of thyroid sarcoidosis revealed by a multinodular
goiter and cervical and mediastinal adenopathies. METHODS: We summarize the
clinical presentation of a thyroid sarcoidosis. A review of literature regarding
this topic is also presented. RESULTS: A 48-year-old woman presented dysphagia
without dyspnea. Clinical and radiological explorations find a multinodular
goiter with cervical and mediastinal adenopathies. The symptomatic side of the
goiter and the association with adenopathies justify the surgery. Total
thyroidectomy and mediastinal lymphadenectomy are processed. Histopathological
examination of the thyroid reveal a goiter without malignity, a vesicular nodule,
and non necrotizing granulomas consistent with sarcoidosis, as in the adenopathy.
CONCLUSION: The interest here, is the difficulty to make the diagnostic without
histopathology, between a thyroid cancer with lymphadenopathies and
extrapulmonary sarcoidosis (involving thyroid and adenopathies).
PMID- 27483580
TI - Chondrosarcoma of the hyoid bone: Case report and review of the literature.
AB - INTRODUCTION: Chondrosarcomas are cartilaginous tumors that range from low-grade
tumors with low metastatic potential to high-grade aggressive tumors with
premature and high metastatic rate. Low-grade types have few karyotype
abnormalities and are near-diploid, while high-grade chondrosarcomas originate
from complex karyotypes and are aneuploid. The most common karyotype aberrations
found include 12q13-15 and 9p21 rearrangements. Here, it is presented a case of
chondrosarcoma of the hyoid bone with its image, surgical procedure and
pathological correlation as well as a review of the literature. CASE
PRESENTATION: A sixty-three year old man presented with a large cervical mass
located at submental level. The CT scan revealed a voluminous and well-limited
mass of 5 x 4 x 3 cm located in the suprahyoid region. The operative finding
revealed a grade 2 chondrosarcoma originating from the hyoid bone. DISCUSSION:
Chondrosarcoma of the. hyoid bone is a rare pathology, thus making it difficult
to diagnose. Fine needle biopsies have high diagnostic accuracy, although correct
grading is only obtained 46% of the time. CT scan is the golden standard to
characterize tumor extension and origin. Surgical excision is the treatment of
choice for chondrosarcoma.
PMID- 27483581
TI - Epitympanic osteoma of the middle ear: A case report and literature review.
AB - INTRODUCTION: Contrary to osteomas and exostosis of the external ear canal,
middle ear osteomas are rare benign tumors that are usually revealed by
progressive hearing loss. CASE REPORT: We here report the case of 56-year-old
woman who had a left ear conductive hearing loss. A CT-scan showed a bone-density
tumor in the left posterior epitympanum, hanging up to the tegmen tympani. A
surgical middle ear exploration showed an epitympanic osteoma, confirmed by a
histological exploration. The tumor was left in place and an ossicular prosthesis
was inserted, which permitted a significant gain in the audiogram air-bone gap.
DISCUSSION: Middle ear osteomas are rare benign tumors (31 cases described from
1964), with male preponderance (sex ratio: 1.75). They always present with a
hearing loss, and the diagnosis is made by CT-scan. The treatment is surgical in
cases of significant discomfort and generally produces a good improvement in
symptoms.
PMID- 27483582
TI - [A post-styloid mass revealing a parapharyngeal schwannoma].
AB - INTRODUCTION: The schwannoma of the glossopharyngeal nerve is a rare etiology
among the tumor masses developed in the parapharyngeal space. CASE REPORT: We
report the case of a 33 years old woman in whom a large schwannoma of the left
glossopharyngeal nerve was discovered incidentally on a brain MRI. Respiratory
evolutionary prognosis imposed trans-oral surgical treatment. DISCUSSION: We
discuss the diagnostic and therapeutic strategy for the benign tumors of the
parapharyngeal space. CONCLUSION: The schwannoma of the glossopharyngeal nerve is
a benign rare lesion. The difficulty lies on the surgical strategy and the choice
of the approach. The functional suites are marked by difficulty swallowing and
require intensive speech therapy.
PMID- 27483583
TI - What's the matter with Florida? Healthcare fraud flourishes despite enforcement
efforts.
PMID- 27483584
TI - Providers invest in the next frontier by delving into patients' genetic data.
PMID- 27483585
TI - Big surpluses, big debate: Not-for-profits dominate top 10 list of most
profitable hospitals.
PMID- 27483586
TI - Commercial insurance margins offset rising Medicare losses.
PMID- 27483587
TI - Logistics: The next target in the war on device costs.
PMID- 27483588
TI - Breast cancer screening guidelines spark a racial divide.
PMID- 27483589
TI - The great cost shift.
PMID- 27483590
TI - Guidance on 340B drug program delivers mismatch of policy and priorities from
HHS.
PMID- 27483591
TI - 'Healthcare has a bull's-eye on its back'.
PMID- 27483592
TI - Find the right tech tools for population management.
PMID- 27483594
TI - How anger is fraying the doctor-patient relationship.
PMID- 27483593
TI - GETTING PAID FOR HOME VISITS.
PMID- 27483595
TI - Prepare now before CMS removes the ICD-10 safety net.
PMID- 27483596
TI - Urgent care and how it relates to your practice.
PMID- 27483597
TI - MACRAnomics: A guide for physicians.
PMID- 27483598
TI - Don't skip your security risk assessment.
PMID- 27483599
TI - What single-payer healthcare would mean to doctors.
PMID- 27483600
TI - Still time for Congress to act on healthcare.
PMID- 27483602
TI - Lifelong Learning Opportunities for Personal Growth.
PMID- 27483601
TI - Discovering the Art of Nursing: Meet Judith Kimchi-Woods.
PMID- 27483603
TI - Choosing an Educational Program That is the Right Fit.
PMID- 27483604
TI - Considerations in Choosing Career Goals.
PMID- 27483605
TI - Questions for New President of ONA Sally Morgan.
PMID- 27483606
TI - Reference Proposals: Defining Initiatives for the Biennium.
PMID- 27483607
TI - SPENCER COX: THE LEGACY OF AN ACTIVIST.
PMID- 27483608
TI - CEOs reject veering sharply from ACA's path.
PMID- 27483609
TI - Hospitals push Medicare to soften readmission penalties in light of socio
economic risks.
PMID- 27483611
TI - Hedge fund boss drops CHS, UHS stocks, pares back health insurance investments.
PMID- 27483610
TI - Out-of-network ER pay and charges fuel ire from docs and patients alike.
PMID- 27483612
TI - Tapping new dimensions. Manufacturers, drugmakers see promise in 3-D printing.
PMID- 27483613
TI - Moving patient payment upfront.
PMID- 27483614
TI - What's a new cancer drug worth?
PMID- 27483615
TI - Proposed consolidation among health insurers could be hazardous to the nation's
health.
PMID- 27483616
TI - Helping ex-inmates get Medicaid.
PMID- 27483617
TI - 'Legislation that requires health systems to post their charges ... just doesn't
help'.
PMID- 27483619
TI - Problems with Drugs or Alcohol?
PMID- 27483618
TI - The Top Five Risk Management Principles for Florida Dentists.
PMID- 27483620
TI - Case Study: Process Failures Lead to Patient Harm.
PMID- 27483621
TI - Taking Ownership for Your Leadership. Three Steps to Creating a Culture of
Learning in Your Practice.
PMID- 27483623
TI - The Myth of Philanthropy.
PMID- 27483622
TI - Five Tips to Building a Successful Sleep Practice.
PMID- 27483624
TI - Diagnostic Discussion: Malignant melanoma.
PMID- 27483625
TI - DDS: Double Down Solution to Florida's Access to Care. Florida's DDS Coordinator
Helps Program Grow.
PMID- 27483626
TI - The Myth of More.
PMID- 27483627
TI - [Pyrophosphate in medicine].
AB - In all organisms from bacteria to humans, specific hydrolases--pyrophosphatases-
hydrolyse inorganic pyrophosphate to phosphate. Without this, DNA, RNA and
protein synthesis stops. Pyrophosphatases are thus essential for all life. In
humans, disorders in pyrophosphate metabolism cause chondrocalcinosis and
hypophosphatasia. Currently, pyrophosphate analogues, e.g. alendronate, are in
clinical use in osteoporosis and Paget's disease but also for e.g. complications
of prostate cancer. In bacteria and protozoan parasites, membrane-bound
pyrophosphatases (mPPases), which do not occur in humans, convert pyrophosphate
to a proton or sodium gradient. mPPases, which are crucial for protozoan
parasites, are thus promising drug targets e.g. for malaria and leishmaniasis.
PMID- 27483628
TI - [The latest antipsychotics--novelties or reiteration of the old?].
AB - Both conventional and more recent antipsychotics are effective in the treatment
of hallucinatory and delusional symptoms in psychotic patients. With the
exception of clozapine, no major differences in the efficacy of different
antipsychotics have been found in clinical drug trials. There are, however,
significant differences between drugs in their adverse effects, and the new
antipsychotics or dosage forms introduced over the past ten years actually
provide novel alternatives for the treatment of patients having body weight
issues or cardiometabolic risk factors. Long-acting injections in turn reduce the
need for psychiatric hospital care.
PMID- 27483629
TI - [Update on current care guidelines: Self-medication, Current Care Guideline].
AB - Self-medication should always be temporary. Self-medication can be used to relief
or treat many symptoms and conditions. In general self-medication is safe when
used properly. However all medicines may cause adverse events or have
interactions with other drugs. It is important to consider all used drugs and
other self-medication products when new drugs are added to the medication list.
Persons using the drugs as well as health care personnel should be aware of
benefits and harms of drugs.The guideline has recommendations for 10 symptoms
that are typically treated with self-medication.
PMID- 27483630
TI - [Risk factors and possibilities of prevention of bowel cancer].
AB - The incidence of bowel cancer has doubled over the past 50 years. Although the
treatment outcome has improved, 40% of those affected with the disease still die
from it. Treatment in the terminal phase of the disease is expensive and requires
plenty of resources without resulting in patient recovery. Bowel cancer could
theoretically be reduced by changing the living habits. Focusing of endoscopy
resources to screening of symptomless patients would be a more realistic means.
Because bowel cancer develops through an endoscopically detectable and slow
growing precancerous adenoma, it is possible to reduce massive disease burden
through screening.
PMID- 27483631
TI - [Principles of oncologic drug therapy following surgery for bowel cancer].
AB - Adjuvant chemotherapy for 6 months following curative resection of colorectal
cancer (CRC) reduces recurrence risk and improves survival in lymph node
positive, stage III disease. In stage II CRC the benefit of adjuvant chemotherapy
is smaller and only recommended if high risk prognostic factors are present.
Microsatellite instability in stage II CRC is associated with a favourable
prognosis and when present adjuvant chemotherapy is not needed. Adjuvant
chemotherapy improves disease outcome also in elderly patients (>= 70 years) with
stage III CRC, but is not recommended in stage II disease. Adjuvant chemotherapy
should be started within 8 weeks following surgery.
PMID- 27483632
TI - [Novel techniques in the treatment of rectal cancer].
AB - Rectal cancer is the eighth and tenth most common kind of cancer in men and
women, respectively, with an increasing frequency of occurrence. Together with
cancer of the large intestine it forms the third most common cancer entity.
Surgical therapy is the most important form of treatment of rectal cancer; in
combination with adjuvant therapy it will cure a significant proportion of the
patients and provide relief for tumor-induced hemorrhagic and obstructive
symptoms. The operation has usually been conducted as an open surgery with the
use of simple instruments. In recent times, the operative techniques have become
more versatile, and mini-invasive techniques have resulted in quicker recovery of
the patients from the operation.
PMID- 27483633
TI - [Streamlined treatment pathway for a colorectal cancer patient].
AB - The organization of colorectal cancer patient treatment, the pathway, is an
important component of the quality of care of a large patient group as nearly
3000 colorectal cancer patients are diagnosed and treated annually in Finland. By
designing and describing the whole pathway, the more streamlined approach can be
made and thus improve patient care. Multidisciplinary team work between
colorectal surgeons, oncologists, pathologists and radiologists is flexible team
work, having been proven to improve overall treatment results. This method of
working together is also a good tool for the development of the pathway to a
better organized treatment.
PMID- 27483634
TI - [Imaging of rectal cancer--key to treatment decisions].
AB - The current guidelines (EURECCA consensus statement 2013) for preoperative
imaging of rectal cancer recommend MRI for local staging and CT of the chest,
abdomen and pelvis for detection of distant metastases. High resolution MR
enables preoperative identification of poor prognostic features. These poor
prognostic features are correlated with an increased risk of local recurrence
and/or metastatic disease. MRI enables the preoperative multidisciplinary team to
decide whether a patient benefits from adjuvant therapy and which surgical
technique should be used. A radiological structured report helps clinicians get
the most out of the report and increases the number of optimal reports.
PMID- 27483635
TI - [Multidisciplinary tailoring of therapy of metastatic colon cancer].
AB - Treatment of colon cancer requires multidisciplinary team work. The multitude of
therapies in metastatic colon cancer have led to longer overall survival with
fewer symptoms. Median survival has increased from 5 months with the best
supportive care to 30-40 months in randomized studies, even with curative
treatment in some patients. Tailoring of the treatment is best done by a
multidisciplinary team considering radiotherapy and operation of the primary
tumor, resection of liver, lung and peritoneal metastases, medical treatment
alternatives, palliative care, ablative methods etc. Without skillful surgeons,
oncologists, pathologists, geneticists, radiologists etc. the best treatment
opportunities may be missed.
PMID- 27483636
TI - [What will determine the first-line treatment of a patient with rectal cancer?].
AB - Treatment of a rectal cancer patient is devised by a multidisciplinary expert
team. The first thing to be solved is whether a curative treatment, one slowing
the progression of the disease, or a symptomatic treatment is aimed at. The
extent of the disease is assessed by using whole body CT scan and MR imaging of
the rectum. When aiming at curative treatment, the need for preoperative
radiation therapy and the surgical technique is assessed on the basis of MRI and
clinical examination. The patient's physical condition, associated diseases or
pelvic radiotherapy previously applied due to other diseases may restrict the
choice of treatment. In an advanced disease, cytostatic chemotherapy is usually
the first-line therapy, unless the tumor is obstructing the bowel.
PMID- 27483637
TI - [Is there a threat to ban the herbicide glyphosate?].
PMID- 27483638
TI - [Iodized salt as a supplement - necessary or not?].
PMID- 27483639
TI - [Health promotion program "care for chronic condition" is extended].
PMID- 27483640
TI - [With kinesthetic infant handling for better quality of life].
PMID- 27483641
TI - [Wanderer between the worlds].
PMID- 27483642
TI - [With introduction of the nursing complex measures score the first successes
appeared in nursing].
PMID- 27483643
TI - [Researchers of tomorrow. A visit to the student laboratory of air and space
travel].
PMID- 27483644
TI - [Hospital CIRS net Germany delivers valuable instructions for nursing
organization, delegation and coordination in the nursing and physician realm].
PMID- 27483645
TI - [A happy solution for Gabriel - seriously ill boy may go from the intensive care
unit to his home. Nursing counseling suggested ways and possible help sources].
PMID- 27483646
TI - [What Kind of Physicians are Anesthesiologists?].
PMID- 27483647
TI - [Ultrasound-guided Rectus Sheath Block vs Transversus Abdominis Plane Block in
Children Undergoing Umbilical Hernia Repair].
AB - BACKGROUND: Although many reports describe the usefulness of the rectus sheath
block (RSB) in the umbilical hernia repair, the efficacy of the transversus
abdominis plane block (TAPB) is rarely reported. The purpose of this study was to
compare the efficacy and technique of ultrasound-guided RSB and TAPB in children
undergoing umbilical hernia repair. METHODS: Thirty-four children younger than 12
years of age scheduled for umbilical hernia repair were enrolled in this
prospective observer-blinded randomized clinical trial. They were randomly
assigned either to RSB group (median age, 3.7 years) or TAPB group (median age,
3.8 years). After the induction of general anesthesia with sevoflurane, nitrous
oxide, and oxygen children in both groups received regional anesthesia with 0.3
ml x kg(-1) of 0.25% ropivacaine on each side under ultrasound guidance.
Hemodynamic changes at the skin incision, postoperative pain scores and parental
satisfaction were recorded. Anesthesiologists rated the quality of ultrasound
images and easiness of the block performance. RESULTS: The patients' demographics
of the two groups were similar. There were no significant differences in the time
needed for the block procedure, quality of ultrasound images and the change of
the heart rate and blood pressure at the skin incision between the two groups.
Postoperative pain score (immediately, 2 and 4 hours after the operation), need
for rescue analgesia and satisfaction of the parents also did not differ. There
were no major complications in the patients. CONCLUSION: TAPB provided comparable
perioperative analgesia and easiness of block performance to RSB in the pediatric
umbilical hernia repair.
PMID- 27483648
TI - [Assessment of Fibrinogen Replacement Therapy by the Combined Simulation of the
Fibrinogen Concentration and Fibrin Polymerization].
AB - BACKGROUND: Fibrinogen replacement therapy is effective for attaining
perioperative hemostasis in critical bleeding due to acquired hypofibrinogenemia.
By simulating the fibrinogen level and fibrin polymerization, we compared the
effect of fibrinogen replacement therapy using cryoprecipitate or fibrinogen
concentrate versus the effect of fresh frozen plasma. METHODS: We simulated the
plasma concentration of fibrinogen during fibrinogen replacement therapy in a
model of cardiopulmonary bypass (CPB) and intensive care unit (ICU). We estimated
fibrin polymerization (FIBTEM A10, thromboelastometry) by the simulated
fibrinogen level, and compared this value with the fibrinogen level and FIBTEM in
clinical patients. RESULTS: In the simulation model of CPB and ICU,
cryoprecipitate and fibrinogen concentrate both effectively restored the
fibrinogen level and FIBTEM, compared to fresh frozen plasma. In clinical
patients, the simulated values of the fibrinogen level and FIBTEM after
administering the fibrinogen concentrate were similar to the measured values.
CONCLUSIONS: In the simulation model, which combines the fibrinogen level and
fibrin polymerization, cryoprecipitate and fibrinogen concentrate effectively
normalize the fibrinogen level and fibrin polymerization, compared to fresh
frozen plasma. The fibrinogen concentrate also demonstrated efficacy in treating
hypofibrinogenemia in clinical patients. The combined simulation model is useful
in assessing the efficacy of fibrinogen replacement therapy by cryoprecipitate or
by fibrinogen concentrate.
PMID- 27483649
TI - [Evaluation of the Effects of Remifentanil Doses on Hemodynamics and Perfusion
Index at the Onset of Pneumoperitoneum during Laparoscopic Surgery].
AB - BACKGROUND: The aim of this study was to investigate whether changes in perfusion
index (PI) correlate with non-invasive haemodynamic parameters (HR, BP) following
the onset of pneumoperitoneum under two doses (moderate-dose (MD) and high-dose
(HD)) of remifentanil and to compare its reliability. METHODS: We divided 33
patients who were scheduled for laparoscopic surgery under general anesthesia
into two groups according to the dose of continuously infused remifentanil:
moderate dose 0.5 MUg x kg(-1) x min(1) (MD group, n = 16) and high dose 1.0 MUg
x kg(-1) x min(-1) (HD group, n = 17). Non-invasive blood pressure (NIBP), HR,
and PI were measured before the start of surgery (time 1), after the start of
surgery (time 2), before the start of pneumoperitoneum (time 3), and 1 min after
the stable state of pneumoperitoneum (time 4). RESULTS: PI decreased from the
baseline after pneumoperitoneum in MD group, on the other hand PI did not change
in HD group. Between the two groups, the magnitude of the PI changes was
statistically different although MBP and HR were not statistically different
CONCLUSIONS: PI may be a reliable and easier alternative to conventional
haemodynamic parameters for detection of stress response to pneumoperitoneum
during remifentanil anaesthesia in adult patients.
PMID- 27483650
TI - [Fibrin-related Markers in Acute Phase of Pulmonary Embolism and Deep Venous
Thrombosis].
AB - BACKGROUND: The fibrin-related markers are considered to be useful in diagnosing
pulmonary embolism (PE) and deep vein thrombus (DVT). We measured D-dimer (DD)
and soluble fibrin monomer complex (SFMC) in these cases, in order to examine the
usefulness of these markers. METHODS: PE patients (P group: 14 cases) and DVT
patients (D group : 16 cases) treated in our hospital, were examined. We measured
the value of DD and SFMC on the first visit day and the second day. In PE cases,
comparative examination of the markers were carried out between dead and survived
cases. RESULTS: The value of both markers in P group ware significantly higher
compared with D group, on the second day. There was a significant correlation
between SFMC and DD in P group, but in D group, significant correlation was not
observed. CONCLUSIONS: It seems that measuring DD and SFMC is useful to evaluate
the pathology of PE and DVT.
PMID- 27483651
TI - [The Influence of Preoperative Oral Carbohydrate Administration on Perioperative
Blood Sugar Levels and Patients' Satisfaction].
AB - BACKGROUND: After introducing preoperative oral carbohydrate as a part of
enhanced recovery after surgery (ERAS) protocols, we assessed the influence of
carbohydrate administration on the perioperative blood sugar levels (BS), the
variation of vital signs and patients' satisfaction. METHODS: After IRB's
approval and obtaining patients' consent, patients were divided into two groups;
taking carbohydrate (Group AW) or not (Group NAW). Anesthesia was induced and
maintained with total intravenous anesthesia using propofol, remifentanil and
rocuronium. We measured BS six times during perioperative period. We also
compared blood pressures and heart rates during induction of anesthesia.
Moreover, we carried out questionnaire surveys about degree of satisfaction for
ERAS among patients and nurses. RESULTS: Heart rates were significantly higher in
Group AW (P < 0.05), but there were no significant difference in blood pressures
or BS between the groups. Patients in Group AW had more anxiety for surgeries (P
= 0.003), but more than 85% of patients and nurses were satisfied with
carbohydrates. CONCLUSIONS: The carbohydrate administration had little influence
on the perioperative vital signs. However, we gained high reputations from
patients and paramedics.
PMID- 27483652
TI - [Perioperative Management of a Child with Vocal Adhesion Leading to Unexpected
Difficult Airway].
AB - We report a child with vocal cord adhesion encountered during induction of
anesthesia. A 4-month-old girl was scheduled for bilateral lip plasty. She was
intubated for one week due to pneumonia at the age of 3 days. Hoarseness and
stridor appeared just after extubation. Although laryngo-fiberoptic examination
had been tried several times, otorhinologists could not find any abnormality. We
once decided to postpone the operation because of severe stridor. However,
laryngofiberoptic examination could not reveal any abnormality, and we
rescheduled the operation. Tracheal intubation using laryngoscope was not
possible due to vocal cord adhesion. Finally, 2.5 mm ID tracheal tube was
intubated by using a fiberscope, and lip plasty was performed. The patient stayed
in the ICU for 7 days after surgery. Tracheotomy was performed 3 weeks after the
operation. We should pay attention to stridor in an infant before general
anesthesia, since it suggests severe airway narrowing although laryngo-fiberoptic
examination could not find any abnormalities.
PMID- 27483653
TI - [Successful One-lung Ventilation with a Right-sided Double-lumen Tube in a
Patient with a Right Upper Tracheal Bronchus, who Underwent Left Pneumonectomy
for Left Hilar Lung Cancer].
AB - A 60-year-old male patient with left hilar lung cancer was scheduled to undergo
left pneumonectomy or left sleeve lower lobectomy. Preoperative computer
tomographic and bronchoscopic examinations revealed that the bronchus (B1) to the
right apical segment (S1) was a tracheal bronchus (TB) originating from the
trachea approximately 10 mm above the carina. Because the left main bronchus was
to be dissected, a right-sided double-lumen tube (DLT) was selected to completely
protect the right lung from spillage of secretions or cancer cells from the left
lung. The right-sided DLT was placed so as to fit its lateral opening of the
bronchial lumen to normal upper branches (B2, B3), while sacrificing ventilation
of S1 with an abnormal branch (B1). However, one-lung ventilation (OLV) of the
right lung could not be achieved, since a gas leakage from the opened tracheal
lumen occurred, most probably due to intra-lobar micro-airway communications
between S1 and S2/S3. The DLT was withdrawn until the blue bronchial cuff
occluded the orifice of the TB (B1). Although the upper half of the blue
bronchial cuff appeared above the tracheal carina, OLV through the two bronchial
lumen openings could be achieved due to a specific, slanted doughnut shape of the
blue bronchial cuff and the location of the abnormal branch (B1) approximate to
the carina. Left pneumonectomy using successful OLV was completed safely without
hypoxemia or hypercapnea. Our experience indicates that management of OLV for
patients with a thoracheal bronchus needs special considerations of the exact
location of the TB and intra-lobar micro-airway communications, in addition to
types of scheduled surgical procedures.
PMID- 27483654
TI - [Utility of McGRATH MAC for a Patient with a Large Epiglottic Cyst].
AB - A 76-year-old man with an epiglottic cyst was scheduled for transoral rigid
endoscopic epiglottic cystectomy under general anesthesia. The epiglottic cyst
was found accidentally when he had an operation of radical cystectomy 2 weeks
before. When he had the radical cystectomy, the ventilation through a mask was
easy. He had no subjective respiratory symptoms. We chose rapid induction with
propofol, remifentanl, and rocuronium. When we inserted the McGRATH MAC
laryngoscope, we could only see a big epiglottic cyst not vocal cord but the
pressure on the neck enabled the laryngologist to see the vocal cord. We could
identify the space through which we could insert tracheal tube without touching
the cyst. After the operation, his trachea was extubed.
PMID- 27483655
TI - [Emergent Caesarean Section in a Patient with a Mediastinal Tumor and Von
Recklinghausen Disease: A Case Report].
AB - It is rare to encounter a pregnant patient with a mediastinal tumor, and if the
tumor size increases as the pregnancy progresses, this increase can cause
complications such as airway constriction and vascular occlusion. We report a
case of a pregnant patient diagnosed with von Recklinghausen disease at the age
of seven and diagnosed with a mediastinal tumors just after her present
admission. The impending suffocation progressed and fetal heart rate decreased
during her hospitalization. Her trachea was intubated and she was moved to an
operating room for an emergent cesarean section under general anesthesia. With
this rapid response, we could rescue both patient and infant. If the size of
mediastinal tumor increases as pregnancy progresses, the tumor will cause
suffocation by airway compression from the outside, in addition to specific
airway edema on the inward side. The present case demonstrates that appropriate
desisoins must be made for airway manegement and initiation of surgery.
PMID- 27483656
TI - [Anesthetic Management of Peritonectomy and Extended Operation for Peritoneal
Pseudomyxoma Combined with Massive Ascites].
AB - We report successful anesthetic management of extended operation for peritoneal
pseudomyxoma combined with massive ascites (16.5 l). A 66-year-old man (weight 76
kg) who could not keep a supine position due to massive ascites associated with
peritoneal pseudomyxoma was scheduled for elective peritonectomy and extended
surgery. With the patient in the semisitting position, we administered 3%
sevoflurane to induce loss of consciousness while preserving spontaneous
ventilation. We then performed crush induction with propofol and rocuronium after
topical anesthesia to the tongue base. Tracheal intubation with the Macintosh
laryngoscope was successful. During the operation, we aspirated about 16.5 l of
ascites over 20 l normal saline irrigation. To maintain the body temperature, we
performed both active and passive extracorporeal warming. The operation included
not only total peritonectomy but also distal gastrectomy, right colon resection,
splenectomy, and cholecystectomy. To perform effective postoperative analgesia,
we placed two epidural catheters from the upper and lower thoracic epidural
spaces. The patient was extubated 3 days after operation, and discharged
uneventfully on the 18th postoperative day.
PMID- 27483657
TI - [A Case of EXIT (Ex-utero Intrapartum Treatment) in a Fetus with Prenatal
Diagnosis of a Giant Cervical Tumor: Successful Airway Management but without
Indication of Treatment for a Tumor].
AB - The ex-utero intrapartum treatment (EXIT) is a rare procedure, and often comes as
an emergency surgery. A careful preparation is crucial and a multidisciplinary
team discussion during the prenatal period is necessary because it may be
practically and ethically difficult to plan a surgical treatment for a fetus for
EXIT. An elective caesarean section and EXIT for a fetus with a giant cervical
tumor, which may cause airway obstruction and difficult intubation, were
scheduled. The anesthesiologist tried oral intubation by direct laryngoscope;
however, neither blade nor rigid bronchoscope insertion was impossible as a firm
mass protruded in oral cavity from the left side. Tracheotomy was successfully
performed and the airway was secured. As for maternal anesthesia, adequate
uterine relaxation was obtained by inhalational agents and nitroglycerine. After
ligation of the umbilical cord, anesthesia was maintained with propofol and
fentanyl, and good uterine contraction was provided by infusion of oxytocin. The
duration of EXIT was 44 minutes. The fetal tumor, containing both solid and
cystic components, was 14 centimeters in diameter, and infiltrated into
intracranial space. There was no indication of resection nor chemotherapy for the
tumor. Palliative care was selected, and the neonate died forty days after birth.
PMID- 27483658
TI - [Anesthetic Management of a 69-year-old Patient with Eisenmenger Syndrome for
Abdominoperineal Resection].
AB - Although life expectancy of the patients with Eisenmenger syndrome (ES) is
currently reported to be lower than 40 years, life span of the patients with ES
may be extended because of development of medical care. According to recently
reported middle-aged patients with ES undergoing non-cardiac surgeries, per
operative mortality and morbidity of the patients with ES undergoing non-cardiac
surgeries may be lower than previously thought, and even elderly patients may be
able to undergo major surgeries such as laparotomies for cancers. We described
the anesthetic management of a 69-year-old patient with ES who had undergone
abdominoperineal resection. In the anesthetic management it is important to
maintain adequate blood volumne and systemic vascular resistance and this avoids
increases of right-to-left shunt. Perioperative monitoring of pulmonary arterial
pressure was useful for hemodynamic management. Good pain control and management
of body temperature were also needed for a perioperative course with no adverse
events. The appropriate anesthetic management of the 69-year-old patient with ES
for abdominoperineal resection resulted in the successful perioperative course.
PMID- 27483659
TI - [Acute Postoperative Negative Pressure Pulmonary Edema Caused by the Compression
of Brachiocephalic Artery].
AB - We report a case of negative-pressure pulmonary edema occurring by tracheal
obstruction caused by the brachiocephalic artery. The patient had deformed thorax
with cerebral palsy, which deformed thorax placing the brachiocephalic artery
high over the trachea, resulting in close and tight contact between the artery
and trachea. Additional deformity of the thorax associated with myotonic attacks
after general anesthesia might shorten the distance between the sternal notch and
the vertebral body, resulting in the tracheal obstruction by the artery.
PMID- 27483660
TI - [Safe and Effective Analgesia with Bilateral Continuous TAP Block for a Patient
with Marfan Syndrome after Open Abdominal Aortic Aneurysm Repair].
AB - A patient with Marfan syndrome underwent emergency open abdominal aortic aneurysm
repair. She was referred to our department for postoperative analgesia. Taking
the risk of possible dural ectasia into consideration, we avoided epidural block.
Alternatively, we performed bilateral continuous transversus abdominis plane
(TAP) block with sufficient analgesia. Lumbosacral dural ectasia is frequently
observed in patients with Marfan syndrome. A few reports described that their
fragile dura may contribute to an increased risk of dural puncture and postdural
puncture headache (PDPH). Thus, in planning neuraxial block for a patient with
Marfan syndrome, the possible consequences of lumbosacral dural ectasia should be
considered. A case we herein present shows bilateral continuous TAP block could
be a safe and effective alternative to epidural block.
PMID- 27483661
TI - [The Use of Arginine Vasopressin and PhosphodiesteraseIII Inhibitor for
Circulatory Shock after the Resection of a Massive Adrenal Pheochromocytoma].
AB - A 72-year-old man developed hypertensive crisis five month previously, and was
diagnosed with massive adrenal pheochromocytoma, with a diameter of 14.5 cm.
Preoperative echocardiography revealed normal cardiac function. The open
abdominal surgery was performed under general anesthesia. During manipulation of
the tumor he developed hypertension and tachycardia. Severe hypotension (50/25
mmHg) and mild bradycardia (70 beats x min(-1)) followed the resection of the
tumor. In addition to volume replacement noradrenaline and adrenaline were
administered, but the systolic blood pressure rose only to 60-70 mmHg. In order
to treat vasodilatory shock, we started to administer arginine vasopressin
infusion at 0.03 units x min(-1). His systolic blood pressure rose to 90 mmHg.
The patient was transferred to the intensive care unit (ICU) postoperatively. The
echocardiography revealed diffuse hypokinetic cardiac function. In order to treat
cardiogenic shock, we started to administer olprinone (phosphodiesteraseIII
inhibitor, infusion of 0.1 MUg x kg(-1) x min(-1)). On postoperative day 2,
circulatory shock improved and the patient was discharged from the ICU. In
conclusion, circulatory shock after the resection of a massive pheochromocytoma
was due to the down regulation of alpha and beta adrenergic receptors. The non
adrenergic vasoconstrictor and inotrope were useful for this situation.
PMID- 27483662
TI - [Involuntary Movement of Bilateral Lower Limbs Caused by Epidural Anesthesia: A
Case Report].
AB - Regional anesthesia, especially epidural anesthesia, rarely causes involuntary
movement Here we present a case of a patient who demonstrated myoclonus-like
involuntary movement of the lower limbs during continuous infusion of
ropivacaine, fentanyl, and droperidol through the thoracic epidural catheter.
This movement disappeared when the epidural infusion was stopped, but reappeared
when the epidural infusion was restarted. Naloxone did not eliminate the movement
The patient was thereafter discharged uneventfully. This case and other reports
in the literature suggest that involuntary movement associated with regional
anesthesia is rare and self-limiting. However, careful consideration should be
given to exclude other, potentially dangerous complications.
PMID- 27483663
TI - [Anesthetic Management of Cesarean Section in a Pregnant Woman with Advanced
Tongue Cancer].
AB - It is very difficult to decide the best time to deliver the baby for a pregnant
woman with advanced cancer. We experienced the perioperative and perinatal
management of a 39-year-old pregnant woman with advanced tongue cancer. The
cancer had already metastasized to the lung and lymph nodes. Furthermore a
recurrent thumb-sized tumor was found in her mouth. She had firmly desired to
discontinue all anticancer treatment for protecting the fetus. On the other hand,
her family could not accept her determination yet. Therefore the medical team was
organized with doctors and co-medicals from multiple departments such as
gynecology, pediatrics, radiology, oncology, midwife, psychotherapy and
anesthesiology. After several conferences including herself and family, finally
cesarean section was scheduled for the 30th gestational week. Prepared for
unexpected emergency delivery, airway stenosis was ruled out by fiberoptic
laryngoscopy and the consent for emergency tracheostomy was obtained. The
operation was performed successfully under spinal anesthesia without any severe
troubles. Medical care as a team from early phase enabled elaborate observation
and preparation through the perioperative and perinatal period. Furthermore, it
was efficient to provide satisfaction to the patient and her family as well.
PMID- 27483664
TI - [Anesthetic Management of a Patient who Developed Intraoperative Paroxysmal
Supraventricular Tachycardia with Pulseless Electric Activity].
AB - A 75-year-old woman was scheduled to undergo an ileus operation under general
combined with epidural anesthesia. Preoperative electrocardiogram (ECG) showed
first-degree atrioventricular block. The patient received no preoperative
antiarrhythmic medication. During surgery, paroxysmal supraventricular
tachycardia (PSVT) occurred unexpectedly with radial artery pulsation
disappearing, indicating pulseless electric activity (PEA). After a five-second
episode of PSVT, her sinus rhythm recovered spontaneously. However, the patient
had repeated short duration of PSVT with PEA. Continuous infusion of ultra-short
acting beta-blocker landiolol successfully terminated the PSVT, and sinus rhythm
was restored. Postoperative ECG showed sinus rhythm. This case report indicates
that beta-blocker can be a drug of choice in patients with PSVT associated with
PEA.
PMID- 27483665
TI - [Two Cases of Caudal Alcohol Block for Perineal Pain that Occurred in Cancer End
of-Life].
AB - We experienced two cases of end-of-life cancer patients with perineal pain, whose
pain was relieved by 5 ml absolute ethanol caudal block. Although the first
injection was ineffective, the second injection resulted in significant relief of
pain in both cases. Although the indication should be carefully considered,
alcohol caudal block is an analgesic method worth considering for the end-of-life
cancer patients complaining of perineal pain.
PMID- 27483666
TI - [Pressure Ulcer Caused by Long-term Keeping of the Same Body Position during
Epidural Labour Analgesia].
AB - We report the case of a 34-year-old woman (height: 153 cm, weight : 62.4 kg, non
pregnant weight : 52 kg, uniparous) without underlying diseases who developed
pressure ulcer due to keeping a similar body position during long-term epidural
delivery. Induction of childbirth was started in gestational week 40, causing
reduction of fetal heart rate, which improved after adoption of a right lateral
recumbent position. Severe contractions occurred and epidural labour analgesia
was started. The fetal heart rate decreased again and induction of childbirth was
suspended, but the right lateral recumbent position was maintained. Epidural
administration was continued due to persistent contractions. Next morning,
induction of childbirth was restarted and birth occurred in approximately 6
hours. The right lateral recumbent position was maintained for approximately 20
hours. At childbirth, a pressure ulcer was present in the intertrochanteric part
of the right femur. The causes included insufficient knowledge of medical staff
about the risk of pressure ulcer during epidural delivery, and no position
change. A decreased sensation and blocked motor nerve caused by epidural
anesthesia might have accelerated pressure ulcer development. This case suggests
that preventive measures against pressure ulcer are required in epidural
anesthesia in pregnant women.
PMID- 27483667
TI - [A Case of Rocuronium Anaphylaxis in which Anesthesia was Safely Performed after
Selection of an Alternative Drug after a Skin Test].
AB - We report our experience of a patient with a history of anaphylactic shock
suspected to be caused by rocuronium who was scheduled to undergo hepatic tumor
resection. The patient was a 17-year-old female (height : 166 cm, weight : 46
kg). During general anesthesia at another hospital several years ago, she had an
anaphylactic shock, and rocuronium was suspected to be the offending drug. To
collect information and search for the cause, skin tests were performed for
rocuronium, vecuronium and suxamethonium. She was positive for rocuronium, and
negative for other drugs. At anesthesia induction, we administered vecuronium and
confirmed no development of anaphylaxis before commencement of surgery. In the
perioperative period, she had no symptoms that indicated anaphylaxis. Since there
is potential high cross-reactivity among muscle relaxants, it is important to
perform a test for alternative drugs when a muscle relaxant may be a cause of
anaphylaxis. Selection and administration of an alternative drug should be
carefully performed, even when a skin test is negative for the alternative drug.
PMID- 27483668
TI - [Anesthetic Management of a Patient with Central Core Disease for Scoliosis
Surgery].
AB - Central core disease (CCD) is a dominantly inherited congenital myopathy. CCD is
also associated with muscular and skeletal abnormalities such as abnormal
curvature of the spine (scoliosis), hip dislocation, and joint deformities. CCD
and malignant hyperthermia (MH) are both associated with mutations in the
ryanodine receptor on chromosome 19q13.1. An 11-year-old boy with CCD complicated
with severe scoliosis was scheduled for spinal fusion surgery under general
anesthesia. Furthermore, he had trismus caused by temporomandibular contracture.
He was considered as MH susceptible. Anesthesia was managed with remifentanil and
propofol without using muscle relaxtants and volatile anesthetics. We could
intubate the trachea with Airtraq laryngoscope without any complications. The
perioperative course was uneventful.
PMID- 27483669
TI - [A Case of Acetaminophen Poisoning Associated with Tramcet Overdose].
AB - Tramcet is a mixture of tramadol and acetaminophen. Acetaminophen poisoning may
be caused by excessive intake of Tramcet. A 17-year-old female took excessive
quantity of Tramcet before noon. She reported it herself in the emergency room.
Her main complaint was nausea and dizziness. Acetaminophen may cause liver damage
with dose-dependent manner. Because there was a possibility of acetaminophen
poisoning, we started oral acetylcysteine. She was discharged from hospital 5
days later without side effects of acetylecysteine and liver damage.
PMID- 27483670
TI - [The Formative Years of Modern Anesthesiology in Japan--A Dialogue between Hideo
Yamamura and Akitomo Matsuki].
AB - In a dialogue with Akitomo Matsuki as the moderator, Hideo Yamamura, the first
Professor of Anesthesiology in Japan at the University of Tokyo who had
enormously contributed toward improving the standard of the specialty in Japan,
gave detailed accounts of following topics: his training as a surgeon, Saklad's
lectures in 1950, the establishment of a departmental anesthesia group, the
conversion to anesthesiologist, studying in the United States, the foundation of
the Japan Society of Anesthesiology, movements for the governmental approval of
registered anesthesiologists and the qualification system of board certified
anesthesiologists, international activities in holding the Second Asian
Australasian Congress of Anaesthesiologists in 1966 and the Fifth World Congress
of Anaesthesiologists in 1972, and the opening of pain clinics and the foundation
of its society. Yamamura's accounts illustrate unknown episodes in the history of
the formative period of modern anesthesiology in Japan.
PMID- 27483671
TI - LEVERAGE YOUR VALUE. How to negotiate narrow neworks.
PMID- 27483672
TI - MACRA likely will mean penalties for small practices.
PMID- 27483673
TI - Transitional care management. Billing and coding it the right way.
PMID- 27483674
TI - How physicians can deal with high-deductible plans.
PMID- 27483675
TI - POPULATION HEALTH. Making it work.
PMID- 27483676
TI - New Health IT program continues legacy of Meaningful Use.
PMID- 27483677
TI - Take a step-by-step approach to HIPAA compliance.
PMID- 27483678
TI - THE FUTURE OF THE AFFORDABLE CARE ACT.
PMID- 27483679
TI - The role of private counsel in medical malpractice cases.
PMID- 27483680
TI - Medicare overpayment rule leaves practices scrambling.
PMID- 27483681
TI - Getting the most out of CME on a budget.
PMID- 27483682
TI - GOP Doctors Caucus looking at ambitious 2016.
PMID- 27483683
TI - [Not Available].
PMID- 27483684
TI - [Differential diagnostic considerations using ICD-10 in chronic back pain with
special regard to persistent somatoform pain disorder with somatic and
psychological factors (ICD-10 F45.41)].
AB - It is often difficult to pass an expert opinion in cases of chronic back pain.
This article analyses the differential diagnostic considerations related to
coding various causes in line with ICD-10. It emphasises the I importance of
making a careful distinction between orthopoedic and psychiatric conditions and
disorders. Simultaneous coding of orthopoedic and psychiatric illnesses and
disorders based on a distinct cluster of symptoms necessitates an
interdisciplinary approach that consistently applies the ICD-10 definitions of
mental an behavioural disorders in order to clearly identify the main reason for
a functional impairment in the insurance and sociomedical context. Persistant
somatoform pain disorder with somatic and psychological factors (ICD-10 F45.41)
should be regarded as related to the underlying disease and be used primarily as
an additional and descriptive diagnosis.
PMID- 27483685
TI - [Medical negligence].
AB - Medical negligence is a matter of growing public interest. This review outlines
various aspects of medical negligence: epidemiology, taxonomy, and the risks,
causes, psychology, management and prevention of errors.
PMID- 27483686
TI - [Postvaccinal complication and medical malpractice law].
AB - The case report involves a 38-year-old female patient with muscular atrophy,
paresis and sensory deficits in the right upper limb following several
vaccinations. A legal dispute ensued over whether medical malpractice could have
caused the neurological deficits. Medical malpractice could not be confirmed.
Even vaccinations administered correctly can lead to neurological impairment.
PMID- 27483687
TI - [Quantified self movement--the new mantra of life insurance companies].
AB - Wearables are small personal minicomputers that register biometric data. In such
a way, the insurance industry hopes to create new sales opportunities and
products, and simplify underwriting. Lower premiums will promote the use of
wearables. The related possibilities and unanswered questions are discussed in
this article. Utilisation of big data offers the insurance industry a range of
new opportunities. The benefit must be proven in the future, however.
PMID- 27483688
TI - [Potential for intervention of private health insurers in discharge management
using the example of stroke patients].
AB - The study reveals that stroke patients today can still experience gaps in the
provision of healthcare and fragmented therapy. This is often the case on
transferral from the inpatient to outpatient sector, causing complications that
could be avoided by means of good discharge management across all sectors.
Private health insurance can actively support and positively influence the
treatment process in the form of case management. Individual contact with stroke
patients and their relatives allows for early planning and organisation of the
next steps, and offers patients the support they need during a difficult phase of
life.
PMID- 27483689
TI - [Not Available].
PMID- 27483690
TI - [Not Available].
PMID- 27483691
TI - [Not Available].
PMID- 27483692
TI - [Not Available].
PMID- 27483693
TI - [Not Available].
PMID- 27483694
TI - [Not Available].
PMID- 27483695
TI - ADVANCEMENT REGARDING THE ROLE OF ENDOTHELIUM IN ARTERIAL WALL DYSFUNCTION.
PMID- 27483696
TI - EATING BEHAVIOR IN RESPONSE TO ACUTE STRESS.
AB - Obesity is a medical and social problem with a dramatically increasing
prevalence. It is important to take action since childhood to prevent and treat
obesity and metabolic syndrome. Infantile obesity affects all body systems
starting in childhood and continuing to adulthood. Understanding the impact of
stressors on weight status may be especially important for preventing obesity.
The relationship between stress, eating behavior and obesity is not fully
understood. However, there is evidence that stress causes disorders in
hypothalamic-pituitary-adrenal (HPA) axis, system that regulates both stress and
feeding responses. Also, the response is different depending on the type of
stressors. Chronic stress, especially when people live in a palatable food
environment, induces HPA stimulation, excess glucocorticoids, insulin resistance,
which lead to inhibition of lipid mobilization, accumulation of triglyceride and
retention of abdominal fat.
PMID- 27483697
TI - NEW CLASS OF DRUGS: THERAPEUTIC RNAi INHIBITION OF PCSK9 AS A SPECIFIC LDL-C
LOWERING THERAPY.
AB - Hyperlipidemia is a well-known risk factor for coronary heart disease, the
leading cause of death for both men and women. Current lipid-lowering treatment
is not always efficient, therefore new pharmacological interventions that reduce
LDL cholesterol (LDL-C) have been developed. This paper presents new class of
specific LDL lipid-lowering drugs under investigation in phase II or III clinical
trials. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9),
a key enzyme in cholesterol homeostasis, improve the liver's ability to clear LDL
from the plasma, reducing LDL-C levels. Currently, three monoclonal antibodies
PCSK9 inhibitors (alirocumab, evolocumab and bococizumab) are evaluated in
clinical outcome trials. ALN-PCSsc, the new first-in- class therapeutic RNA
interference (RNAi) inhibitor of proprotein convertase subtilisin/kexin type 9
(PCSK9) is also the first-in-class investigational medicine that acts by turning
off PCSK9 synthesis in the liver. The development leadership of ALN-PCSsc has now
transferred from Alnylam Pharmaceuticals to The Medicines Company, who has
initiated the ORION-1 Phase II study at the beginning of 2016. ALN-PCSsc has
significant potential given its highly competitive profile as compared with
monoclonal antibodies anti-PCSK9 MAbs, a recently approved class of LDL-C
lowering drugs.
PMID- 27483698
TI - SCORING IN ACUTE PANCREATITIS: WHEN IMAGING IS APPROPRIATE?.
AB - Acute pancreatitis (AP) is a frequent presentation to the emergency departments
with a rising incidence and a great variability in clinical severity and outcome.
The aim of this review is to offer a succinct presentation on acute pancreatitis
scoring systems and the use of different imaging methods in severity prediction:
Ranson criteria, Glasgow criteria, Hong Kong Score, Acute Physiology and Chronic
Health Evaluation II (APACHE II), computed tomography scoring systems, Bedside
Index of Severity in Acute Pancreatitis (BISAP) score, Panc 3, Japanese Severity
Score (JSS), Harmless Acute Pancreatitis Score (HAPS), Pancreatitis Outcome
Prediction (POP), Sequential Organ Failure Assessment (SOFA). This article also
describes the Revised Atlanta Classification of AP (2012) and the correlation
with computed tomography.
PMID- 27483699
TI - INFLUENCE OF SLEEP ON OBESITY IN CHILDREN.
AB - Childhood obesity is a global epidemic with long term implications. The main
cause of obesity is an increase in calorie intake and a decrease in physical
activity, but also there is clear evidence suggesting a link between the duration
and quality of sleep and obesity risk. Good sleep habits are involved in
increased ability to concentrate at school, improvement of general state, immune
system development, increased quality of life. On the other hand, there are
several mechanisms by which chronic sleep deprivation induces weight gain:
disturbance of hormones that control hunger center, increased time for meals,
reduced physical activity, metabolic changes. Recently, nighttime sleep duration
has declined, in contrast with the increasing prevalence of obesity. Childhood
sleep habits have a long term effect on weight, with repercussions even into
adulthood. This is the reason why there is increasing interest to include sleep
quality on the list for childhood obesity prevention. Sleep represents an
important and independent risk factor of obesity in children and adolescents and
it should be taken into consideration in the management of obesity.
PMID- 27483700
TI - MUSCULOSKELETAL IMPAIRMENT IN PRYMARY HYPOTHYROIDISM.
AB - This article contains bibliographical data concerning the rheumatic clinical
manifestations in hypothyroidism: polyarthralgias, lack of recent skill of fine
movements of the hands, carpal tunnel syndrome or tarsal, degenerative
arthropathy or acute type (gout, chondrocalcinosis), adhesive capsulitis (frozen
shoulder syndrome), generalized muscular stiffness, hypothyroid myopathy,
secondary osteoarthritis, Dupuytren's contracture, "trigger finger" (also called
as stenosing tenosynovitis or trigger thumb) etc. and data on the short history,
epidemiology, of these disorders. Review include 60 bibliographical sources.
PMID- 27483701
TI - POTENTIAL NEW ROLES OF LEPTIN IN HEALTH AND DISEASE.
AB - Leptin is an adipose-tissue specific cytokine described 20 years ago and
classically thought to be involved in regulation of food intake and energy
homeostasis. More recently, leptin was proven to exert other multiple roles in
carbohydrate and lipid metabolism, reproductive system, and inflammatory and
immune reactions. Emerging data propose leptin to be a modulator of bone mass. In
some particular circumstances leptin synthesis follow specific patterns in
inflammation and sepsis, not being proportional with fat mass. Therefore, it may
be used as diagnostic or prognostic marker for critical illness.
PMID- 27483702
TI - TREATMENT OF METABOLIC ALTERATIONS IN POLYCYSTIC OVARY SYNDROME.
AB - Polycystic ovary syndrome is a common endocrinopathy characterized by oligo
ovulation or anovulation, signs of androgen excess and multiple small ovarian
cysts. It includes various metabolic abnormalities: insulin resistance,
hyperinsulinemia, impaired glucose tolerance, visceral obesity, inflammation and
endothelial dysfunction, hypertension and dyslipidemia. All these metabolic
abnormalities have long-term implications. Treatment should be individualized and
must not address a single sign or symptom. Studies are still needed to determine
the benefits and the associated risks of the medication now available to
practitioners.
PMID- 27483703
TI - MEDICAL PRACTICE IN CHILDREN PRESENTING FEVER WITH PETECHIAL RASH TO AN EMERGENCY
DEPARTMENT.
AB - INTRODUCTION: The association of fever and petechiae in children is one of the
most alarming findings for a paediatrician. To quickly distinguish between benign
and life-threatening conditions is challenging in many cases. We aimed to
evaluate the clinical practice of children presenting with fever and petechiae as
initial symptoms. METHODS: 41 patients (age 3 months-11 years) presenting with
fever and petechiae were identified in an Emergency Paediatric Assessment Unit
over a period of 9 months. General data, symptoms and signs were assessed for
each patient. The work-up consisted in: complete blood count, inflammatory tests,
coagulation tests, Monospot test, nasopharyngeal rapid tests, blood culture, and
cerebrospinal fluid culture where appropriate. RESULTS: Most children were <5
years of age (70.7%). Female to male ratio was 1:2.4. The most common clinical
diagnoses were: viral respiratory illness (48.8%, 20/41) and upper respiratory
tract infection (17.1%, 7/41). Meningococcal disease was found in one case. CRP>6
mg/l was poorly correlated with serious illness. The following variables were
strongly associated with serious illness: ill appearance, shivering, lethargy,
back rigidity, ESR>50 mm/h and prolonged capillary refill time. 59% (24/41) of
children were treated with antibiotics, however, at discharge 42%(10/24) of them,
did not have a work-up suggestive for a bacterial illness. CONCLUSIONS: Screening
for low prevalence but high morbidity conditions, as the meningococcal disease,
with an extensive work-up is time and resource consuming and may lead to
unmotivated antibiotic use. Larger studies are needed to change the emergency
practice for management of fever and rash.
PMID- 27483704
TI - ANATOMICAL AND CLINICAL ORBSERVATIONS ON STRUCTURAL CHANGES OF THE HIP JOINT.
AB - The hip, the second largest joint of the human body, with its primary
contribution to locomotion, is exposed to numerous traumatic or non-traumatic
risks. Regardless of the initial pathology, there is always almost the same
result: diminution of range of motion, onset of pain and functional impotence, as
well as change of biomechanics of walking. Through its high frequency, morpho
functional imbalance (clinically expressed both imagistic and biologically, in
one or several joints), osteoarthritis is a disease with a multifactorial
etiology and a complex pathogeny. MATERIAL AND METHOD: The study included 244
patients aged between 18-85 years, clinically and paraclinically investigated,
especially for the osteoarthritis of the hip, admitted to Rheumatology Clinic I,
Rehabilitation Hospital in Iasi, from January 2012 to December 2014. RESULTS AND
DISCUSSION: The high prevalence of degenerative diseases of the joints in old age
is analyzed in accordance with the results of the estimations, which showed that,
in fact, most of the patients remain undetected, undiagnosed and untreated. Main
symptoms are pain in the coxofemoral joint, radiating or not on the lateral or
anterior face of the thigh down to the knee, morning stiffness after a long rest,
limping or walking with small steps, and muscle atrophy of the group of muscles
that are responsible for the stability of the joint. CONCLUSIONS: A strict
discipline is needed from the patient's side, in order to keep and apply the
doctor's indications in a chronic disease that requires a long therapy, on one
hand; on the other hand, a close cooperation between various experts is needed,
in order to customize and apply the most effective program, at the right time.
PMID- 27483706
TI - CORTICOSTEROID TREATMENT IN THE SETTING OF DECOMPENSATED LIVER CIRRHOSIS WITH
RELATIVE ADRENAL INSUFFICIENCY: A CASE REPORT AND A BRIEF REVIEW OF THE
LITERATURE.
AB - Relative adrenal insufficiency (RAI) is the term used to describe inadequate
production or action of glucocorticoids with respect to the severity of the
illness. RAI is frequently found in critically ill patients particularly with
septic complications and it is also present in both critically ill and stable
patients with liver cirrhosis. In the following study a case report of a patient
with decompensated cirrhosis and RAI is presented followed by a brief review of
the literature. A 65-year-old male with liver cirrhosis of alcoholic etiology was
admitted to hospital with bilateral leg edema, ascites, and marked weakness. At
admission, his blood pressure was 82/52 mmHg and he had sinus tachycardia of
130/min. Laboratory analysis revealed hyponatremia (122 mmol/L), while ascites
fluid analysis showed no infection. During the first 48 hours of hospitalization
the patient remained persistently hypotensive despite adequate vascular filling
and the addition of noradrenaline. A standard-dose short synacthen test was
performed which revealed a poor cortisol response, which is a compatible
criterion for the diagnosis of RAI. Intravenous hydrocortisone therapy was
initiated, which resulted in a rapid improvement in patient's general condition,
and increase in blood pressure. As the patient became hemodynamically stable
without the need of noradrenaline, the hydrocortisone dose was weaned
progressively, and he was discharged after 18 days of hospitalization in a stable
condition.
PMID- 27483705
TI - EXTRADIGESTIVE MANIFESTATIONS OF GASTROESOPHAGEAL REFLUX DISEASE: DEMOGRAPHIC,
CLINICAL, BIOLOGICAL AND ENDOSCOPIC FEATURES.
AB - Gastroesophageal reflux disease (GERD) with extradigestive manifestations is a
disorder increasingly recognized both by gastroenterologists, pneumologists,
otolaryngologists and cardiologists. AIM: To evaluate the demographical,
clinical, biological and endoscopic features of the patients with
gastroesophageal reflux disease and extradigestive manifestations (chronic
laryngitis, asthma, pseudoangina). MATERIAL AND METHODS: Prospective case-control
study, including 137 patients selected from patients referred to the Iasi
Institute of Gastroenterology and Hepatology between July 2014-September 2015. In
the presence of typical GERD symptoms (heartburn or regurgitation), the patients
were assessed by upper digestive endoscopy for the detection or exclusion of
esophagitis. Despite the absence of esophageal lesions, the patients were further
assessed by impedance-pHmetry. RESULTS: Depending on the dominant extradigestive
manifestation, the patients were assigned into 3 groups: 94 chronic laryngitis
patients, 24 asthma patients and 19 pseudoangina patients. Females were more
frequent among pseudoangina patients (68.4%). Mean age of the male patients with
dysphonia or asthma was lower (p=0.002), the majority (78.1%) living in urban
areas. Obesity was predominant in pseudoangina group (52.6%), as compared to
dysphonia group (16%) the differences being statistically significant (p=0.002).
A share of 57.9% of pseudoangina patients were dyslipidemic, in contrast to
dysphonia (24.5%) or asthma group (37.5%) (p=0.013). Esophagitis was also more
frequent at pseudoangina group (84.2%), but with no significant statistical
difference between the study groups (79.8% and 75%, respectively) (p=0.115). It
seems that Helicobacterpylori infection tends to be protective in patients with
GERD and pseudoangina (RR=0.61), but it can not be extrapolated to the general
population (p=0.459). CONCLUSION: GERD with extradigestive manifestations is a
prevalent and heterogeneous disease. There are demographic, clinical, biological
and endoscopic differences between patiens with extradigestive GERD.
PMID- 27483707
TI - THE "DARK SIDE" OF DEEP VEIN THROMBOSIS--CASE REPORT.
AB - Venous thromboembolism (VTE) is an increasingly common cause of morbidity and
mortality in cancer patients. In various malignancies the incidence of thrombosis
ranges from 5% to 60%, that is four times higher in cancer patients compared to
the general population. Large retrospective studies have shown that in men the
tumors which are most commonly associated with VTE are lung cancer and pancreatic
cancer and, in women cancer of the genital area, pancreas, colon and rectum.
Thromboembolic events may often occur before the cancer diagnosis. We present the
case of a 41-year-old female patient with a history of genital cancer which was
surgically treated and who is now admitted for clinical signs of ileofemoral deep
vein thrombosis (DVT) of the left leg. The diagnosis was confirmed by laboratory
data and Doppler ultrasound and the patient received anticoagulant treatment.
Given the history of the patient, abdominal and pelvic ultrasound and computer
tomography (CT) were performed to detect the cause who predisposed to the
thrombotic event. These confirmed the ovarian cancer, this time on the right
side, and the presence of hepatic and pulmonary metastasis. This case highlights
the importance of screening for a cause of the thromboembolic event in patients,
especially in those who have a history of a neoplasia.
PMID- 27483708
TI - NEUROPSYCHOLOGICAL GROUNDS IN THE AWAKE BRAIN SURGERY.
AB - Traditionally, the awake cerebral neurosurgical interventions are carried out
when the primary motor areas and the areas involved in language are concerned.
This procedure is also known as mapping (Intraoperative Brain Mapping). The
intraoperative neuropsychological protocol supposes the setting of a list of
steps and tasks that the patient must perform during the surgery, taking into
account the lesion localization (both the cortical and the subcortical
structures), the cognitive functions involved and the individual particularities
of each patient. As a result of the high validity of certain tests, we propose a
common minimal set of tests, which can allow a minimal standardization and
replicability.
PMID- 27483709
TI - VENOUS ULCER--A NEW THERAPEUTIC APPROACH.
AB - Trophic leg ulcer is a major health problem affecting approximately 1-2% of the
population, the incidence being higher in the elderly (70-80 years). It is a
multifactorial condition, but the most common cause is chronic venous
insufficiency. This can be attributed to reflux in the saphenous system and calf
perforator vein incompetence. These were first described by Linton, the first
intervention designed to correct perforator vein incompetence bearing his name.
Today Linton's operation has been abandoned due to the large unaesthetic incision
and great postoperative pain. Also, ulcer healing time is long (2 months) and
recurrence rate is high. Currently a series of minimally invasive procedures are
used to close these perforator veins, such as ultrasound-guided sclerotherapy.
The advantages of these techniques are less discomfort to the patients, low rate
of complications, short hospital stay.
PMID- 27483710
TI - CLASIC VERSUS NOVEL IN REDUCTION OF ACUTE ANTERIOR DISLOCATION OF THE SHOULDER: A
COMPARISON OF FOUR REDUCTION TECHNIQUES.
AB - AIM: The purpose of our study is to compare four different techniques for
reduction shoulder dislocation in term of efficacy, duration until reduction and
pain felt by patient during the procedure. MATERIAL AND METHODS: During 2015
year, we conducted a study on 50 chronological patients with anterior shoulder
dislocation. After exclusion of four patients, the remaining 46 (74% males, mean
age 44.6 +/- 20.03 years, range 18 to 89) were randomly assigned in four groups
and reduced by Cunningham (C), Kocher (K), Mothes (M) and Hipocrat (H)
techniques. All the patients were sedated using Midazolam (2 mg) and Fentanyl (1
microg/kgbw) except patients who underwent Cunningham technique. RESULTS: The
success rate was 76.9% in C group, 98.4% in K group, 90.2% in M group and 87.96%
in H group (p>0.05). The level of pain in C group was similar to the other groups
in the absence of pain medication (p<0.05). CONCLUSIONS: Cunningham technique is
a simple, single person technique, drug free, less painful and safer, comparable
with other "classical" methods.
PMID- 27483711
TI - BILATERAL BREAST CANCER: DIAGNOSIS AND PROGNOSIS.
AB - AIM: To assess bilateral breast cancer patients, initially diagnosed with stage
II unilateral breast cancer. MATERIAL AND METHODS: 113 patients with stage 0-II
breast cancer diagnosed between 1983 and 2011 were assessed. Of these, 8 patients
had bilateral breast cancer: 7 patients with metachronous bilateral breast cancer
and 1 patient with synchronous breast cancer. Breast ultrasound, mammography,
computed tomography and magnetic resonance imaging were used to diagnose
recurrence, loco regional and distant metastasis. RESULTS: Age at diagnosis
ranged from 37 to 59 years, with a maximum age incidence in the 4th decade (age
between: 31-40 years). The average time interval between the two breast cancers
was 8.125 years. The most common histological type was invasive ductal carcinoma.
All eight patients with bilateral breast cancer had at least one type of
recurrence/metastasis, mostly in the liver, and statistically the pleuropulmonary
and liver metastases were the most frequent causes of death. CONCLUSIONS:
Patients in the 4th decade diagnosed with unilateral breast cancer are at risk of
developing bilateral breast cancer. In metachronous breast cancer, the time
interval between the detection of the second breast cancer and death is directly
proportional to the time interval between the two breast cancers. TASTASES,
DEATH.
PMID- 27483712
TI - COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN
FIBROCYSTIC MASTOSIS.
AB - AIM: Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most
treatments for fibrocystic mastosis are: hormonl, with beneficial results and non
hormonal, with fluctuating results. MATERIAL AND METHODS: A number of 210 cases
were studied, which were divided into 7 groups. The study lasted for 9 months and
it was carried out on the basis of a personal examination sheet. The following
were monitored: age groups, mastodynia, reducing breast nodules, a significant
reduction in the volume of the mastosic cysts, reducion of the fibrous tissue,
medication tolerance. RESULTS: Mastodynia has declined by 90% in the cases
treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and
Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the
advantages and disadvantages of drugs (contraindications, side effects), age
category, breast pain reduction, antiproliferative activity, tolerability,
relapse allow us to assess the benefit-risk. Even in those circumstances that
remained incompletely clarified for objective reasons, related to the
inaccurate/incorrect reporting by the patients, there is a significant difference
(p < 0.05) between the frequency of relapses following the treatment with
Tamoxifen and the other categories of drugs who were administered. CONCLUSIONS:
Our study shows that in the groups that were administered Logest, Utrogestan and
Bromocriptine, only antalgic effects were achieved (disappearance or only
decrease of mastodynia) and no anti-proliferative effects were obtained.
Basically, hormone treatment should be made based on a histopathological
examination.
PMID- 27483713
TI - OUTCOMES OF SURGERY IN PROLIFERATIVE VITREORETINOPATHY.
AB - AIM: To present the anatomical and functional outcomes of surgery in cases of
rhegmatogenous retinal detachment complicated (at presentation) by proliferative
vitreoretinopathy (PVR). MATERIAL AND METHODS: Retrospective study of the cases
operated upon by a single surgeon between October 2012 and September 2014.
RESULTS: A total of 49 eyes of 49 patients had PVR at presentation (12 cases with
PVR stage B, 21 with stage C and 16 with stage D). 82% had a VA < or = 0.05 at
presentation. Peripheral retinectomy was the primary surgery in 57% of cases.
Reinterventions was required in 16.3% of the cases (silicon oil extraction was
not considered reintervention). Although at the first postoperative examination
32% of eyes had an IOP > 21 mmHg without medication, only 8% retained a high lOP
at the last visit. At the last visit 73.4% of eyes presented attached retina (an
additional 6% had an attached macula under silicone oil, but sub retinal fluid in
the inferior quadrants). A final VA > or = 0.05 was recorded in 67.3% of eyes (of
which half had VA > or = 0.1) CONCLUSIONS: In cases presenting with retinal
detachment complicated by PVR the possibility of reinterventions and the risk of
intraocular hypertension should be considered. Unfortunately, even some cases
with favorable anatomical outcome will not present ambulatory vision. Keywords:
PMID- 27483714
TI - EARLY COMPLICATIONS FOLLOWING ANATOMIC LUNG RESECTIONS--EXPERIENCE OF A THORACIC
SURGICAL ONCOLOGY UNIT.
AB - AIM: To analyze the medical and socioeconomic impact of the complications of
anatomic lung resections performed at the Thoracic Surgery Unit of the Iasi
Regional Cancer Institute. METHODS: This retrospective study included patients
who underwent anatomic lung resections between January 2013 and August 2015.
RESULTS: Over this interval a total of 172 major lung resections were performed:
31 (18.02%) pneumonectomies, 5 (2.91%) bilobectomies, and 136 (79.06%)
lobectomies. Complications occurred in 36 patients, including bronchial stump
fistula in 7 patients (4.06%), bronchopneumonia (9/5.23%), pleural empyema
without bronchoscopically documented bronchial stump fistula (1/0.58%),
chylothorax (1/0.58%), postoperative arrhythmia (3/1.74%), early postoperative
stroke (1/0.58%), prolonged air leak (requiring hospital stay longer than 14
days) (11/6.38%), and postoperative hemothorax requiring reintervention
(3/1.74%). Secondary to complications, a number of 3 (1.74%) patients died early
postoperatively. CONCLUSIONS: The incidence of immediate and early postoperative
complications is comparable to those reported by other authors.
PMID- 27483715
TI - INFLUENCE OF GLAUCOMA ON DIABETES-INDUCED CHANGES IN THE ANTERIOR OCULAR SEGMENT.
AB - AIM: To monitor the influence of glaucoma on the changes caused by diabetes in
the anterior ocular segment. MATERIAL AND METHODS: Prospective, comparative
clinical study, which included the patients with glaucoma and diabetes assessed
at the Iasi "Sf. Spiridon" Hospital, "Euro Medi Center" Clinic and "Oftaprof"
Clinic. The study included a number of 142 patients, divided into two groups: 67
patients with glaucoma and diabetes (study group) and 75 patients with diabetes
mellitus (control group). Upon enrollment the patients were subjected to a
complete assessment of their ophthalmologic and metabolic status. Monitored
aspects: prevalence of lens changes, extent of ocular surface disease and
identification of the changes in corneal biomechanical parameters in the patients
with glaucoma and diabetes. RESULTS: In both monitored groups, the cortical lens
changes prevailed, both at the beginning and at the end of the study, with no
statistically significant differences between groups (p>0.05). The risk of
developing lens changes reaches 50% in the patients who have had diabetes for 20
years. In the patients in the study group, tear secretion was significantly lower
at the end of the study (Schirmer's test values 11.61 vs. 10.67 mm, p=0.045).
Tear film instability was present in 37.3% of the patients. Corneal hysteresis
(CH) and comeal resistance factor were significantly reduced in the group with
glaucoma and diabetes, as compared to the group with diabetes (p=0.001).
CONCLUSIONS: There is significant ocular surface disease in the patients with
glaucoma and diabetes, as compared to those with diabetes alone. Glaucoma and the
number of antiglaucoma drugs are associated with a significant reduction in tear
secretion. The association of glaucoma resulted in the reduction in CH and
corneal resistance factor in the patients with glaucoma and diabetes as compared
to the healthy ones.
PMID- 27483716
TI - LEFT ATRIAL, LEFT ATRIAL APPENDAGE AND PULMONARY VEINS ANATOMICAL VARIANTS IN
PATIENTS WITH ATRIAL FIBRILLATION VERSUS PATIENTS IN SINUS RHYTHM.
AB - The aim of the study is to evaluate by multidetector computed tomography (MDCT)
the prevalence, location and size of LA (left atrial) diverticula and accessory
appendages, the prevalence of PVs anatomical variants and LAA (left atrial
appendage) shapes in patients with atrial fibrillation (AF) compared to patients
in sinus rhythm (SR). Images obtained by MDCT in a group of 100 patients with <1
year paroxysmal or persistent AF prior to radiofrequency catheter ablation and in
a group of 100 patients in SR with unconfirmed or insignificant (<50%) coronary
arteries stenoses were compared. The prevalence of LA diverticula (22% in AF
group, 19% in SR group) and accessory appendages (6% in AF group, 5% in SR group)
was not significantly different between the two groups. Similar sizes of LA
diverticula and accessory appendages were registered in patients with AF and in
SR. The prevalence of a common left venous trunk was significantly higher in
patients with AF (30%) compared to patients in SR (18%) (p=0.047) and proved to
be an independent predictor for AF (odds ratio (OR) 1.32; 95% confidence interval
(CI) 0.93-1.51; p=0.002) at multivariate logistic regression. LAA had a complex
shape but no significant differences concerning the prevalence of the 4 major
types were registered between the groups. In conclusion, the only parameter
associated with AF was the presence of a left common trunk suggesting that it is
either a consequence or a predisposing factor for the development of AF.
PMID- 27483717
TI - IMMUNOHISTOCHEMISTRY IN ENDOMETRIAL HYPERPLASIA AND ENDOMETRIAL ADENOCARCINOMA.
AB - AIM: Endometrial hyperplasia is a proliferation of endometrial glands due to the
prolonged stimulation with estrogens of the endometrium that occurs in women
receiving exogenous estrogens, with anovulatory cycles, or in patients with
ovarian tumours with estrogen secretion. MATERIAL AND METHODS: The study
performed by the authors included 575 patients with endometrial hyperplasia and
163 patients with endometrial adenocarcinoma admitted to the "Cuza-Voda"
Obstetrics and Gynaecology Clinical Hospital of Iasi, between 2005-2007. RESULTS:
There were selected, for these immunohistochemistry reactions, 22 cases of simple
hyperplasia without atypia, 26 cases of complex hyperplasia without atypia, 23
cases of endometrial adenocarcinoma of endometrioid type, well differentiated, 22
cases of endometrial adenocarcinoma of endometrioid type, moderately
differentiated, and 19 cases of non-endometrioid adenocarcinomas represented by
nine clear cells and 10 serous endometrial adenocarcinomas. Estrogen receptors
have been positive in about 85-90% of the tumour cells of the well-differentiated
endometrial adenocarcinomas of endometrioid type (GI). In endometrioid-type
endometrial adenocarcinomas moderately differentiated (GII), the estrogen
receptors were positive in approximately 70-85% of the tumour cells. CONCLUSIONS:
Endometrial hyperplasia, especially complex endometrial hyperplasia with atypia,
increase the risk for endometrial adenocarcinoma, and their early detection
becomes mandatory under cancer prevention. Well-differentiated endometrioid
endome- trial adenocarcinomas were ER and PR-positive, so that the ER expression
correlated with the PR expression. Well-differentiated endometrioid endometrial
adenocarcinomas (GI) in the studied group also showed a higher content of ER and
PR compared to the endometrial moderately-differentiated endometrioid endometrial
adenocarcinomas (GII). In nonendometrioid adenocarcinomas, represented by clear
cell endometrial adenocarcinomas, the ER content was reduced and the PR
expression was negative. Serous adenocarcinomas failed to show an
immunohistochemically expression for ER and PR.
PMID- 27483718
TI - THE RELEVANCE OF CYTOLOGICAL DIAGNOSTIC IN THE MAMMARY GLAND CANCER.
AB - Breast cancer is the second leading cause of cancer death in women, while in
Eastern Europe the most common form of diagnosed cancer. Out of the multiple
possibilities of early detection of mammary neoplasia that have been elaborated,
only mammography has proved to be a simple, efficient method and of a high
sensitivity, almost 90% However, the cytological confirmation of diagnosis allows
us to perform the preoperative radiotherapy treatment or poly chemotherapy.
MATERIAL AND METHODS: we analyzed the informative value of these diagnosis
methods in stage I mammary gland cancer (MGC). In this way, in the present paper
we demonstrated that collecting samples through fine-needle aspiration biopsy
allows the cytological confirmation of the diagnosis of stage I MGC in 30.7%
cases. RESULTS AND DISCUSSION: In stage I MGC young patients, under 35 years, the
cytological confirmation rate is 22.2% and is lower as compared to the
cytological confirmation rate in patients older than 35 years which is 37.9%
Also, for a tumor diameter < 0.5 cm, the prevalence of cytological confirmation
was only 10.3%, while for the diameter of 0.6-1.0 cm the cytological confirmation
was around 40.0%. Therefore, in order to improve the cytological diagnosis
confirmation rate the tumor biopsy through the USG of the mammary glands is
required. Moreover, the cytological investigation of the smear obtained by the
first and second puncture was instrumental in confirming the diagnosis in 41.3%
and 17.4% cases; the subsequent repetition of the punctures was not useful as it
helped to confirmation of the diagnosis only in 9.3% cases. The frequency of
diagnosis cytological confirmation depends on the tumor histopathological form
and type of growth. CONCLUSIONS: Thus, the lowest prevalence was in the mixed
forms--12.5% cases, lobular cancer--24.4% cases, while regarding the type of
growth, for the rare forms the cytological confirmation rate was 7.7% and 31.5%
cases for the schiros growth type.
PMID- 27483719
TI - PANCREATIC CANCER CT IMAGING: COMPARISON WITH SURGERY.
AB - AIM: To establish the best protocol for pancreatic computer tomography and
criteria for staging (mainly for vascular invasion). MATERIAL AND METHODS: Our
research included 49 consecutive patients with pancreatic cancer examined at the
Iasi "Sf. Spiridon" Hospital between January and December 2014 with a Siemens 16
Emotion CT unit. CT protocol included no enhanced CT and pancreatic phase of the
superior abdomen, portal venous phase of the abdomen and pelvis. RESULTS AND
DISCUSSION: The study patients were stratified into 5 age groups and the most
frequently affected by pancreatic cancer were the patients aged 60 to 79 years.
For T staging the extension in the per pancreatic fat tissue, into surrounding
organs (5 patients had extension in other organs) and vessels was evaluated. We
determined the degree of contact between the tumor and the artery, thrombosis and
deformity of the veins and we have found 8 resettable lesions, 28 tumors in stage
T3 and 13 pancreatic cancers in stage T4. Thirty-three patients had
lymphadenopathies and 31 of them had distant metastases. CONCLUSIONS: Our study
proved that computed tomography is a good method of examination for pancreatic
cancer when the right imaging protocol is used; during the pancreatic phase the
arteries and the tumor are well depicted, liver metastases are best evaluated
during the portal venous phase. The best criterion for arterial invasion is tumor
contiguity with more than half of vessel circumference, and for vein invasion
deformity or thrombosis. Comparison with surgical staging was o good backup for
the radiologist and depicted several differences with imaging staging, more often
understating than over staging.
PMID- 27483720
TI - MANAGEMENT OF BILATERAL FEMORAL NECK FRACTURE IN A NONAGENARIAN PATIENT--CASE
REPORT.
AB - Simultaneous bilateral femoral neck fracture is rare injury. Cases with this type
of fracture have been reported in the literature since the 1950s, following the
introduction of electroconvulsive therapy which generates violent hip muscle
contractions. In young patients' simultaneous bilateral femoral neck fracture
results from high energy trauma (car accident or fall from height) in a normal
bone. Pathological changes in bone structure occurring in chronic kidney disease,
vitamin D deficiency, osteomalacia, osteoporosis, metabolic imbalances and
administration of corticosteroids explain the occurrence of this particular type
of fracture following low-energy trauma. We present the case of a 90-year-old
female patient who suffered a simple fall from her own height resulting in a
Garden IV bilateral femoral neck fracture. Our therapeutic option in this patient
was bilateral uncemented bipolar hemiarthroplasty in a single session using a
single tray of sterile surgical instruments and two sterile drapes. Postoperative
outcome was very good, allowing the initiation of functional recovery on the
first postoperative day. Uncemented hemiarthroplasty proved to be a good choice
in such a patient in the associated diseases may trigger the risk of
cardiovascular disturbances specific to bone cement implantation syndrome.
PMID- 27483721
TI - COMBINED APPROACH FOR LARGE TUMORS OF THE NOSE AND PARANASAL SINUSES--CASE
REPORT.
AB - Due to the insidious onset and common symptoms, the diagnostic of sinonasal
tumors is late in the evolution. Usually, at that time, the preferred endoscopic
approach alone is not recommended, therefore a mixed openendoscopic approach
appears to be the best choice in terms of exposure of the tumor and a clear
margin resection. The purpose of this case report study is to demonstrate the
necessity of careful preoperative assessment and the advantages of combined
approach for a complete resection and favorable long-term results.
PMID- 27483722
TI - SURGICAL TREATMENT OF POSTPARTUM ILIOFEMORAL DEEP VEIN THROMBOSIS--CASE REPORTS.
AB - The writing committee for Antithrombotic Therapy for Venous Thromboembolic
Disease of the 2008 ACCP guidelines made the following recommendations for
thrombus removal strategies in patients with deep vein thrombosis (DVT): open
surgical thrombectomy is recommended in patients with acute iliofemoral DVT to
reduce symptoms and post-thrombotic morbidity; whenever available, catheter
directed thrombolysis is preferred to surgical venous thrombectomy, the risk of
hemorrhage being diminished; surgical venous thrombectomy is recognized to be
efficient in cases where catheter-directed thrombolysis is unavailable or the
patients are not suitable candidates for such a procedure. Randomized studies
comparing surgical thrombectomy and anticoagulant therapy in patients with
iliofemoral DVT (IFDVT) showed that at 6 months, 5 years, and 10 years the
patients in the thrombectomy group presented increased permeability, lower venous
pressure, less edema, and fewer postthrombotic symptoms compared to the patients
receiving anticoagulant therapy. In this article we present 3 cases of IFDVT in
postpartum patients diagnosed by Doppler ultrasound of the deep venous system.
The 3 patients received anticoagulant therapy prior to surgery. Surgery consisted
in thrombectomy of the common, superficial and deep femoral veins, external and
internal iliac veins, and femoral-saphenous arteriovenous fistula. The patients
received postoperative antithrombotic therapy and were followed-up at 3, 6 and 9
months by Doppler ultrasound of the deep venous system.
PMID- 27483723
TI - ADENOCARCINOMA AND TUBERCULOSIS OF THE SIGMOID COLON AND FALLOPIAN TUBE--A RARE
ASSOCIATION. A CASE REPORT AND REVIEW OF THE LITERATURE.
AB - Association of adenocarcinoma and tuberculosis (TB) of the sigmoid colon is a
rare clinical condition even in an endemic country as Romania, with challenging
diagnosis and treatment. Case report. We present the case of a 57-year-old female
patient who was admitted on emergency basis for a diagnosis of obstructive
sigmoid adenocarcinoma. The patient was operated on and it an obstructive sigmoid
tumor with serosal invasion, adherent (invading) to the body of uterus and left
adnexa and urinary bladder serosa, no liver or peritoneal metastases. A
sigmoidectomy was performed "en bloc" with subtotal hysterectomy, left
adnexectomy and extramucosal cistectomy. The histopathological exam showed a
moderately differentiated, ulcerated adenocarcinoma, widely infiltrating the
colon wall invading the myometrium. Ziehl Neelsen (ZN) stain identified the
presence of metachromatic bacillary structures in the colonic wall, lymph nodes
and adnexal areas. Postoperative course was uneventful and the patient was
discharged 10 days postoperatively in good clinical condition. After one year
when the patient completed the full course of anti-tubercular drugs, a thorough
work-up was performed. Colonoscopy, CT of the thorax, abdomen, pelvis showed no
signs of recurrence while tumoral marker CEA (1.62 ng/ml - n<3.4) and QFT
(Quantiferon-TB Gold) test were within normal range. Discussion and conclusion.
Although digestive tuberculosis is included in differential diagnosis for those
patients presenting abdominal pain or obstructive digestive symptoms in endemic
regions, in this case the absence of TB infection criteria and positive
endoscopic biopsy for colonic adenocarcinoma did not allow a complete pre- or
perioperative diagnosis.
PMID- 27483724
TI - PELVIC ACTINOMYCOSIS MIMICKING A LOCALLY ADVANCED PELVIC MALIGNANCY--CASE REPORT.
AB - We present the case of a former user of an intrauterine contraceptive device
(IUD) for 10 years, diagnosed with a bulky, fixed pelvic tumor involving the
internal genital organs and the recto sigmoid, causing luminal narrowing of the
rectum, interpreted as locally advanced pelvic malignancy, probably of genital
origin. Intraoperatively, a high index of suspicion made us collect a sample from
the fibrous wall of the tumor mass, large Actinomyces colonies were thus
identified. Surgery consisted in debridement, removal of a small amount of pus
and appendectomy, thus avoiding a mutilating and useless surgery. Specific
antibiotic therapy was administered for 3 months, with favorable postoperative
and long-term outcomes. Pelvic actinomycosis should always be considered in the
differential diagnosis of pelvic tumors in women using an IUD. The association of
long-term antibiotic treatment is essential to eradicate the infection and
prevent relapses.
PMID- 27483725
TI - MITOCHONDRIAL MYOPATHY: A NEW THERAPEUTIC APPROACH.
AB - Restoration of deoxyribonucleic acid in mitochondrial myopathies may occur after
a mechanical or chemical injury of striated muscle or by endurance training.
Therapies with enzymes, gene therapies, or treatments with substances that
stimulate mitochondrial biogenesis are used at the moment. Genesis of
mitochondria may also come from myonuclei by releasing the nuclear respiratory
factor-1/2 during muscle contractions. Multiplying of myonuclei depends on muscle
satellite cell activation. Since the electromyostimulation increase the number of
circulating stem cells that may participate in the genesis of new muscle fibers
(adding to the deposit of specific stem cells of the muscle), and intermittent
hypoxia stimulates the proliferation of muscle satellite cells, we propose to
combine the two processes for the treatment of mitochondrial myopathies.
Respective combined therapy may be useful for restoring damaged mitochondria by
drug side effects.
PMID- 27483726
TI - VITAMIN D AND TISSULAR EXPRESSION OF VITAMIN D RECEPTOR IN OBESITY.
AB - Vitamin D (VitD), a lipid-soluble hormone, is able to regulate the transcription
of many genes through vitamin D receptor (vitD receptor-VDR). It has been shown
that VitD deficiency is associated with obesity, characterized by a low degree
inflammatory state, which contribute to the pathogeny of metabolic syndrome and
type 2 diabetes mellitus. VitD deficiency is a public health problem, at the same
time the global prevalence of obesity and cardiovascular diseases is continuously
growing. Evidence from recent studies on animal models suggest that VitD or VDR
deficiency promotes cardiomyocyte hypertrophy, which can be one of the mechanisms
for increasing cardiovascular risk. The heart is one of the target organs of
action for VitD, because VDR is expressed in cardiomyocytes. Also, previous in
vitro studies have shown that VitD is able to inhibit the production of monocyte
chemotactic factors (MCP-1) and other pro-inflammatory mediators in human
preadipocytes and mature adipocytes. Inflammation is an important factor in the
pathogenesis of atherosclerosis. In obesity there are not known data about
correlations between plasma levels of VitD and VDR expression in the subcutaneous
fat tissue, epicardial visceral adipose tissue, and in particular in myocardium.
Also, there are still no studies to test VDR expression in myocardial cells and
to investigate the results of dietary VitD supplementation on the expression of
VDR in the epicardial adipose tissue and myocardium.
PMID- 27483727
TI - CONSIDERATIONS ON ANATOMY AND PHYSIOLOGY OF LYMPH VESSELS OF UPPER AERO DIGESTIVE
ORGANS AND CERVICAL SATELLITE LYMPH NODE GROUP.
AB - The almost constant local regional development of the cancers of upper aero
digestive organs requires the same special attention to cervical lymph node
metastases, as well as to the primary neoplastic burning point. The surgical
therapy alone or associated has a mutilating, damaging character, resulting in
loss of an organ and function, most of the times with social implications,
involving physical distortions with aesthetic consequences, which make the
reintegration of the individual into society questionable. The problem of
cervical lymph node metastases is vast and complex, reason why we approached
several anatomical and physiological aspects of lymph vessels of the aero
digestive organs. Among the available elements during treatment, the headquarters
of the tumour, its histologic degree, and its infiltrative nature, each of them
significantly influences the possibility of developing metastases.
PMID- 27483728
TI - STRESS IN PEDIATRIC PATIENTS--THE EFFECT OF PROLONGED HOSPITALIZATION.
AB - Long-term hospitalization emotionally impacts any patient, especially children,
and is defined as a long period of time during which the patient is hospitalized
and experiences isolation from his or her family, friends and home. Stressful
situations trigger a nonspecific response that involves multiple physiological
mechanisms. Currently, because of the complexity of these mechanisms, there are
no laboratory markers that allow the quantification of the stress intensity felt
by the patient. Laboratory determinations currently used in evaluating the
response to stress are neuroendocrine, immunological and metabolic. The
neuroendocrine system is the first to respond to stressful events. Stress
stimulates the hypothalamus, leading to the release of CRH, which stimulates the
pituitary gland to produce ACTH. Chronic stress directs the synthesis towards
cortisol, which may lead to hypo secretion of the other adrenal steroid hormones.
The hospital and the disease are stressors for children and caregivers, since
stress can interfere with the normal development of young patients, affecting
them in the long term. Admitting a child to hospital means interrupting his or
her normal daily life and changing the environment that is familiar to him or
her. Therefore, the involvement of the family doctor is very important, as many
conditions can be solved by visiting his or her office and thus eliminating the
need for hospitalization in a pediatric hospital. If, however, the nature of the
condition requires that the child should be seen by a pediatrician, the period of
hospitalization should not be much extended so as to prevent the appearance of
other possible problems that might influence the child's state.
PMID- 27483729
TI - EPIDEMIOLOGIC RESEARCH REGARDING THE IMPACT OF RISK FACTORS ON HEALTH-RELEATED
QUALITY OF LIFE IN CANCER PATIENTS.
AB - AIM: To assess the health-related quality of life in cancer patients and the
relative and attributable risks for the degree of dissatisfaction related to
intrinsic and extrinsic factors. MATERIAL AND METHODS: Our research included 128
cancer patients treated at the Surgical Clinic II of the Iasi Regional Cancer
Institute between December 2014 and June 2015. Thus, data were collected by using
an inquiry sheet derived from the SF-36 questionnaire, which included closed and
open questions about the quality of life, socioemographic data and such risk
factors as smoking, alcohol use, related diseases and risk behaviours. Results:
The patient sample had a mean age of 60.85 years, 51.6% of them lived in urban
areas, were high school graduates, and of low economic status. DISCUSSION: As to
the behavioural risk factors we found that over 80% of the patients were non
smokers, did not use alcohol, and were normal weighted. Pain was experienced by
70.7% of the cancer patients and depression affected 74% of the study cases.
Patients were asked to self-assess their own health status on a scale of 0
(worst) to 100 (the best health status). CONCLUSIONS: Our study showed a poor
health status (mean score 65) in the study cancer patients. The relative and
attributable risks for the degree of dissatisfaction related to intrinsic and
extrinsic factors were calculated and ranked factors in decreasing order:
smoking, depression, pain, alcohol use, male gender, obesity, low income. We
found that prolonged'suffering affects the psyche and causes depression and that
the patients of low financial status, most of them living in villages, have
difficulty in accessing medical care. The obtained data about the quality of life
in relation with risk factors are in agreement with the data in the literature.
PMID- 27483730
TI - ALCOHOL CONSUMPTION WITH FAMILY PATTERN RELATED TO STRONG PERSONALITIES: A CASE
CONTROL STUDY IN MARRIED ROMANIAN STUDENTS.
AB - In the study conducted the aim was to investigate strong personalities (SP)
related to alcohol consumption in married students from Romania. MATERIAL OF
STUDY: Consisted in 2 samples: a case-sample (23 alcohol consumer students with a
family pattern of weekly consumption, 47.8% male and 52.2% female, aged 21-29
years) and a control-sample (42 no-alcohol consumer students without a family
pattern of consumption, 26.2% male and 73.8% female, aged 21-29 years), selected
from a sample of 176 married students. METHOD: An observational inquiry (case
control) consisted in applying 2 questionnaires: Health Questionnaire (60 items,
7: Q43-Q49 -alcohol consumption) and Strong Personalities Questionnaire (88
items, alpha-Crohnbach index-0.823). Statistical analysis was performed by the
aid of SPSS 20 Program. RESULTS: For alcohol consumer students with weekly
pattern of consumption the main reason of alcohol consumption was curiosity
(60.9%) and the most frequent consumed alcohol was beer (38.6%, 500-3000
ml/week). Personalities' profiles revealed V-hyperthymic, III-hyperperseverant
and X-emotive strong personalities (SP) as being symptomatic (over 50%
symptomatic level-SL) for both samples, with a difference (control-case) for X
emotive SP (71.7% students--57.1% students, respectively). I-demonstrative, VII
cyclothymic and IV-unruly SP presented a difference between case (symptomatic:
61.8%; 61.8% and 61.8% students, respectively) and control (symptomatic: 36.8%;
37.5% and 45% students, respectively) samples. A statistically significant
difference case-control samples was demonstrated for I-Demonstrative (item S29:
chi square chi2 = 10.65; Sig.0.002; gamma correlation gamma=0.73; Sig.0.002) and
for X-emotive (item S25: chi2 = 8.76; gamma = -0.66; Sig.0.003) SP. In
conclusion, a relation SP-alcohol consumption in married students is suggested.
PMID- 27483731
TI - EVALUATION OF THE SYNTHESIS AND STRUCTURE OF NEW AZETIDIN-2-ONES OF FERULIC ACID.
AB - AIM: To synthesize some new azetidin-2-ones of ferulic acid and to evaluate them
from physicochemical and spectral point of view. MATERIAL AND METHODS: The
synthesis was carried out in several steps: (i) obtaining the ferulic acid
chloride; (ii) obtaining the ferulic acid hydrazide with hydrazine hydrate (98%);
(iii) condensation of ferulic acid hydrazide with different benzaldehydes (2
hydroxy-/2-nitro-/4-chloro-/4- fluoro-/4-bromo-benzaldehyde) in order to obtain
the corresponding hydrazones; (iv) cy- clization of ferulic acid hydrazones with
chloroacethyl chloride in freshly distilled toluene medium and in the presence of
triethylamine, resulting in the corresponding azetidin-2-ones. RESULTS: Six new
azetidin-2-ones of ferulic acid were synthesized. They were characterized in
terms of their physicochemical properties and their structure was confirmed by IR
and 1H-NMR spectroscopy. CONCLUSIONS: Six new azetidin-2-ones of ferulic acid
were synthesized, physicochemically characterized and validated spectrally. A
PMID- 27483732
TI - EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.
AB - L-Arginine is an a-amino acid which plays important roles in different diseases
or processes, such as Alzheimer disease, inflammatory process, healing and tissue
regeneration and it also could be useful as an anti-atherosclerotic agent. AIM:
Considering the large amount of studies on the beneficial effects of different
antioxidants, this paper is focused on the evaluation of the antioxidant
potential of some imine derivatives, synthesized by the authors and described in
a previous article. MATERIAL AND METHODS: The evaluation of the antioxidant power
was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric
reducing antioxidant power (FRAP) assays, tests described in the literature and
which are used with some minor modifications. RESULTS: It was found that most of
the imine derivatives are more active than the L-Arginine in the PPAP and FRAP
assays. The most active derivative was the compound obtained by condensation of L
arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g).
CONCLUSIONS: Following the described protocol, some imine derivatives of L
arginine were evaluated in terms of antioxidant potential using in vitro methods.
The most favorable influence was obtained by the aromatic substitution with nitro
and hydroxyl, the corresponding derivatives being the most active derivatives
compared to L-arginine.
PMID- 27483733
TI - INFLUENCE OF CARBOXYMETHYLCELLULOSE SODIUM AND LUTROL ON THE SWELLING INDEX AND
DISINTEGRATION TIME OF BIOMUCOADHESIVE TABLETS WITH MICONAZOLE NITRATE.
AB - PURPOSE. To develop original pharmaceutical formulation with miconazole nitrate,
biomucoadhesive tablets, used in antifungal medication. MATERIAL AND METHODS: The
oral biomucoadhesive tablets with miconazole nitrate were developed by direct
compression of the excipient mixture: carboxymethylcellulose sodium and lutrol
6000, excipients used for bioadhesivity, mannitol as a sugar substitute and
aerosil as a lubricant. The main goal of the study is to determine the
disintegration time and the swelling index of biomucoadhesive tablets with
miconazole nitrate in order to estimate the time of contact with mucosa,
respectively the prolongation of drug substance release. RESULTS: The swelling
index was calculated depending on time in all the 5 formulations that included
the carboxymethylcellulose sodium and Lutrol 6000 as matrix-forming, and the
studied were time and association ratio between polymers. CONCLUSIONS: Analysing
the results, we noticed that out of the four excipients we used,
carboxymethylcellulose sodium had the higher influence on the swelling index and
disintegration time.
PMID- 27483734
TI - IN VITRO MEASUREMENT OF TOTAL ANTIOXIDANT CAPACITY OF CRATAEGUS MACRACANTHA LODD
LEAVES.
AB - Crataegus macracantha Lodd, family Rosaceae, is a very rare species in Europe,
and unlike Crataegus monogyna is less investigated for pharmacologic activity.
AIM: To analyze the ability of the lyophilisate of extract obtained from leaves
of Crataegus macracantha Lodd (single plant at the Iasi Botanical Garden) to
capture free radicals in vitro. MATERIAL AND METHODS: The lyophilisate obtained
in Department of Pharmacognosy, Faculty of Pharmacy, "Grigore T. Popa" University
of Medicine and Pharmacy Iasi. The decreased absorbance of chromophore
chlorpromazine radical cation in the presence of the lyophilized solutions was
studied spectrophotometrically. The indicator radical cation, obtained by
oxidation of chlorpromazine by potassium persulfate, has the maximum absorbance
at 525 nm. Ascorbic acid was used as a standard antioxidant. RESULTS: The
absorbance of radical solution was determined after the addition of a certain
amount of lyophilisate at different time intervals. The antioxidant activity was
calculated using the calibration curve obtained by plotting the variation in
radical solution absorbance depending on ascorbic acid concentration. For each
ascorbic acid concentration the area under the curve was calculated from plotting
the percentage inhibition of the absorbance at two pre-established time
intervals. CONCLUSIONS: The results confirm the antioxidant activity of the
leaves of Crataegus Macracantha Lodd and by optimizing the proposed analytical
methods the antiradical activity can be quickly evaluated with minimal reagent
consumption.
PMID- 27483735
TI - CATECHINS PROFILE, CAFFEINE CONTENT AND ANTIOXIDANT ACTIVITY OF CAMELLIA SINENSIS
TEAS COMMERCIALIZED IN ROMANIA.
AB - AIM: Catechins profile, caffeine content and antioxidant activity of different
green tea and white tea samples commercialized on the Romanian market were
investigated. MATERIAL AND METHODS: Five green tea samples and five white tea
samples commonly available on the Romanian market were processed by infusion and
the lyophilisates of infusions were analyzed. Total phenolic content was
determined using the Folin-Ciocalteu method. Catechins and caffeine profile was
analyzed by RP-HPLC-DAD (Agilent Eclipse XDB-C18 column, binary mobile phase (A)
3% acetic acid and (B) methanol). In vitro antioxidant activity was assessed by
free radical scavenging and ferrous ion chelating assays. RESULTS AND
DISCUSSIONS: Total phenolic content ranged between 44.73 +/- 0.63 and 63.57 +/-
0.45 GAE% in green tea samples and between 9.69 +/- 0.90 and 52.99 +/- 0.45 GAE%
in white tea samples. RP-HPLC-DAD analysis allowed the identification of
epigallocatechin gallate (45.18-118.58 mg/g lyophilisate) and caffeine (47.79
108.07 mg/g lyophilisate) in all tea samples; epicatechin was detected in all
samples (5.04-31.04 mg/g lyophilisate) except for two white teas infusions. Green
tea samples scavenged DPPH radical and chelated ferrous ion with EC50=9.68 +/-
0.02-16.11 +/- 0.02 microg/mL and 10.91 +/- 0.04-18.65 +/- 0.03 microg/mL,
respectively. For white teas, EC50 values varied between 9.50 +/- 0.02-20.95 +/-
0.02 microg/mL in DPPH assay and 12.49 +/- 0.03-20.32 +/- 0.07 microg/mL in
ferrous ion chelating assay. CONCLUSIONS: This study showed a large variability
in the content of catechins and caffeine and in the antioxidant capacity of both
green and white tea samples.
PMID- 27483736
TI - LOW LEVELS OF SERUM CYANOCOBALAMIN IN A METFORMIN-TREATED PATIENT. CASE REPORT
AND COMPARISON WITH LITERATURE DATA.
AB - Metformin is a widely used oral antidiabetic biguanide compound. According to the
literature, metformin may lower the serum cyanocobalamin levels. We present the
case of a 71-old-male treated with metformin for 15 years. When presenting to a
periodic checkup, low serum cyanocobalamin levels where found. Laboratory tests
showed levels below normal range for hemoglobin (12.7 g/dL) and hematocrit
(37.8%). After patient reevaluation, a change in antidiabetic treatment will be
considered if metformin will be found the cause of low serum cyanocobalamin
levels. Other cases reported in the literature support this hypothesis,
justifying the study of the influence of metformin therapy on serum vitamin B12
levels in patients diagnosed with diabetes. The influence of patient age,
metformin dosage, duration of treatment and time since diabetes diagnosis on
serum levels of vitamin B12 also need to be determined.
PMID- 27483737
TI - Andrew Herxheimer: his life's work, to be continued.
PMID- 27483738
TI - Phonological Encoding in Mandarin Chinese: Evidence from Tongue Twisters.
AB - Models of connected speech production in Mandarin Chinese must specify how
lexical tone, speech segments, and phrase-level prosody are integrated in speech
production. This study used tongue twisters to test predictions of the two
different models of word form encoding. Tongue twisters were constructed from 5
sets of characters that rotated pairs of initial segments or pairs of tones, or
both, across format (ABAB, ABBA), and across position of the characters in four
character tongue twister strings. Fifty two native Mandarin Chinese speakers read
aloud 120 tongue twisters, repeating each one six times in a row. They made a
total of 3503 (2.34%) segment errors and 1372 (.92%) tone errors. Segment errors
occurred on the onsets of the first and third characters in the ABBA but not ABAB
segment-alternating tongue twisters, and on the onsets of the second and fourth
characters of the tone-alternating tongue twisters. Tone errors were highest on
the third and fourth characters in the tone-alternating tongue twisters. The
pattern of tone errors is consistent with the claim that tone is associated to a
metrical frame prior to segment encoding, while the format by position
interaction found for the segment-alternating tongue twisters suggest
articulatory gestures oscillate in segment production as proposed by gestural
phonology.
PMID- 27483739
TI - Tune in to the Tone: Lexical Tone Identification is Associated with Vocabulary
and Word Recognition Abilities in Young Chinese Children.
AB - Lexical tone is one of the most prominent features in the phonological
representation of words in Chinese. However, little, if any, research to date has
directly evaluated how young Chinese children's lexical tone identification
skills contribute to vocabulary acquisition and character recognition. The
present study distinguished lexical tones from segmental phonological awareness
and morphological awareness in order to estimate the unique contribution of
lexical tone in early vocabulary acquisition and character recognition. A sample
of 199 Cantonese children aged 5-6 years was assessed on measures of lexical tone
identification, segmental phonological awareness, morphological awareness,
nonverbal ability, vocabulary knowledge, and Chinese character recognition. It
was found that lexical tone awareness and morphological awareness were both
associated with vocabulary knowledge and character recognition. However, there
was a significant relationship between lexical tone awareness and both vocabulary
knowledge and character recognition, even after controlling for the effects of
age, nonverbal ability, segmental phonological awareness and morphological
awareness. These findings suggest that lexical tone is a key factor accounting
for individual variance in young children's lexical acquisition in Chinese, and
that lexical tone should be considered in understanding how children learn new
Chinese vocabulary words, in either oral or written forms.
PMID- 27483740
TI - Priming Implicit Prosody: Prosodic Boundaries and Individual Differences.
AB - Using the structural priming paradigm, the present study explores predictions
made by the implicit prosody hypothesis (IPH) by testing whether an implicit
prosodic boundary generated from a silently read sentence influences attachment
preference for a novel, subsequently read sentence. Results indicate that such
priming does occur, as evidenced by an effect on relative clause attachment. In
particular, priming an implicit boundary directly before a relative clause--cued
by commas in orthography--encouraged high attachment of that relative clause,
although the size of the effect depended somewhat on individual differences in
pragmatic/communication skills (as measured by the Autism Spectrum Quotient).
Thus, in addition to supporting the basic claims of the IPH, the present study
demonstrates the relevance of such individual differences to sentence processing,
and that implicit prosodic structure, like syntactic structure, can be primed.
PMID- 27483741
TI - Asking or Telling--Real-time Processing of Prosodically Distinguished Questions
and Statements.
AB - We introduce a targeted language game approach using the visual world, eye
movement paradigm to assess when and how certain intonational contours affect the
interpretation of utterances. We created a computer-based card game in which
elliptical utterances such as "Got a candy" occurred with a nuclear contour most
consistent with a yes-no question (H* H-H%) or a statement (L* L-L%). In
Experiment I we explored how such contours are integrated online. In Experiment 2
we studied the expectations listeners have for how intonational contours signal
intentions: do these reflect linguistic categories or rapid adaptation to the
paradigm? Prosody had an immediate effect on interpretation, as indexed by the
pattern and timing of fixations. Moreover, the association between different
contours and intentions was quite robust in the absence of clear syntactic cues
to sentence type, and was not due to rapid adaptation. Prosody had immediate
effects on interpretation even though there was a construction-based bias to
interpret "got a" as a question. Taken together, we believe this paradigm will
provide further insights into how intonational contours and their phonetic
realization interact with other cues to sentence type in online comprehension.
PMID- 27483742
TI - Social Expectation Improves Speech Perception in Noise.
AB - Listeners' use of social information during speech perception was investigated by
measuring transcription accuracy of Chinese-accented speech in noise while
listeners were presented with a congruent Chinese face, an incongruent Caucasian
face, or an uninformative silhouette. When listeners were presented with a
Chinese face they transcribed more accurately than when presented with the
Caucasian face. This difference existed both for listeners with a relatively high
level of experience and for listeners with a relatively low level of experience
with Chinese-accented English. Overall, these results are inconsistent with a
model of social speech perception in which listener bias reduces attendance to
the acoustic signal. These results are generally consistent with exemplar models
of socially indexed speech perception predicting that activation of a social
category will raise base activation levels of socially appropriate episodic
traces, but the similar performance of more and less experienced listeners
suggests the need for a more nuanced view with a role for both detailed
experience and listener stereotypes.
PMID- 27483743
TI - Abstract and Lexically Specific Information in Sound Patterns: Evidence from /r/
sandhi in Rhotic and Non-rhotic Varieties of English.
AB - Phonological theories differ as to whether phonological knowledge is abstract
(e.g., phonemic), concrete (e.g., exemplar-based), or some combination of the
two. The abstractness/concreteness of phonological knowledge was examined by
analyzing the process of /r/-sandhi in two corpora of spoken English. Two
predictions of exemplar-based theories were examined: the extent to which a word
manifests a particular sound pattern like /r/-deletion should be influenced by
(1) its lexical frequency and (2) its distribution in the language with respect
to the sound pattern's conditioning environment. Lexical frequency was found to
influence /r/-sandhi in a corpus of rhotic American English but not in a corpus
of predominantly non-rhotic British English. No effect of a word's long-term
distribution was found in either corpus. These results support theories proposing
that phonological knowledge is both word-specific and abstract and indicate that
speakers do not store all phonetic detail that is in principle available to them.
The factors that may favor the use of word-specific versus abstract
representations are discussed.
PMID- 27483744
TI - Generalization of Phonetic Detail: Cross-Segmental, Within-Category Priming of
VOT.
AB - The current study examined whether fine-grained phonetic detail (voice onset time
(VOT)) of one segment (/p/ or /k/) generalizes to a different segment (/t/)
within the same natural class. Two primes were constructed to exploit the natural
variation of VOT: a velar stop followed by a high vowel (keen) resulting in a
naturally long VOT and a labial stop followed by a low vowel (pan) resulting in a
naturally shorter VOT. Two experiments were conducted, one in which the speakers
produced both the prime and the target, and a second in which the speakers heard
the primes and then produced the targets. In Experiment 1, VOTs for initial /t/
were shorter following pan than following keen. In Experiment 2 where
participants heard the primes, priming was found only when the primes had
unexpected relative VOT values (short for keen and long for pan). These results
provide evidence for cross-segmental generalization of phonetic detail and also
suggest that natural, within-category variability is encoded during language
processing.
PMID- 27483745
TI - A Special Section on The Role of Nanotechnology for Sustainable Energy and
Environment.
PMID- 27483746
TI - A Review on Quantitative Measurement of Cell Adhesion Strength.
AB - There is an explosion of interest in characterizing cell adhesion process and the
mechanochemical players that is critical to a wide range of physiological and
pathological consequences. Much, however, still remains uncertain and
controversial about the quantitative measurement of cell adhesion strength (i.e.,
cell-substratum adhesion force, cell-cell adhesion force, etc.). The main reason
for this deficit is a lack of well-established and comprehensive experimental
methods that quantitatively measure cell adhesion strength at cellular and even
molecular levels. This leads to the need for conducting a literature review on
the methods for characterizing the adhesion force of anchorage-dependent cells.
In this review article, we discern and critique available techniques for
measuring cell adhesion strength that is required for an adherent cell (or cells)
of interest to detach from the neighboring cell or the substratum. This review
focuses on recent advances in the technique for measuring cell adhesion strength
to weigh up the strengths and weaknesses of each technique, together with a brief
description for the biological aspects of cell adhesion process. The summary of
this article might help us both to develop a standard method for measuring cell
adhesion strength and to broaden and deepen our understanding of cell adhesion
process.
PMID- 27483747
TI - Recent Advances in Nanoplasmonic Sensors for Environmental Detection and
Monitoring.
AB - The great attention in environmental pollution urges the development of
innovative monitoring system enabling rapid, sensitive, specific detection and
easy operation. Recent progress in nanoplasmonic sensors allowing real-time,
highly-sensitive, label-free and multiplex detection provides a promising
alternative to conventional environmental analyzing techniques. This review
summarizes novel nanoplasmonic approaches categorized by optical detection
technologies, which include surface plasmon resonance spectroscopy, dark-field
nanospectroscopy, Raman spectroscopy, and even naked eyes. The focus of this
review will be on how plasmonic nanostructures can be utilized to detect
environmental pollutants, and remarkable accomplishments to enhance the detection
performances. In addition, we discuss current challenge and future direction for
ubiquitous environmental sensing and monitoring.
PMID- 27483748
TI - Review of Molecular Simulations of Methane Storage in Metal-Organic Frameworks.
AB - Methane storage in porous materials is one of the hot issues because it can
replace dangerous high-pressure compressed natural gas (CNG) tanks in natural gas
vehicles. Among the diverse adsorbents, metal-organic frameworks (MOFs) are
considered to be promising due to their extremely high surface areas and low
crystal densities. Molecular simulation has been considered as an important tool
for finding an appropriate MOF for methane storage. We review several important
roles of molecular modeling for the studies of methane adsorption in MOFs.
PMID- 27483749
TI - CO2 Adsorption Over Metal-Organic Frameworks: A Mini Review.
AB - Metal-organic frameworks (MOFs) are a class of porous materials that are
comprised of metal ion-containing nodes linked by multi-dentate organic ligand
bridges principally through coordination bonding. Over the last few decades, MOFs
have been studied widely as CO2 adsorbents. CO2 adsorption in MOFs can be
enhanced by tuning their physicochemical properties. This short review discusses
CO2 adsorption over MOFs with particular focus on the contributory effects of (1)
inherent textural properties, (2) coordinatively unsaturated open metal sites,
(3) surface functionalization, (4) structural interpenetration (catenation), and
(5) ion-exchange.
PMID- 27483750
TI - Synthesis of TiO2 Materials Using Ionic Liquids and Its Applications for
Sustainable Energy and Environment.
AB - Titanium dioxide (TiO2) has received significant attention because of the global
climate change and the consumption of fossil fuel resources. Specifically, using
TiO2 in photocatalytic applications, such as the removal of organic pollutants
and a hydrogen production has become an important issue. Thus, many researchers
have attempted to prepare highly active TiO2 materials using various synthetic
approaches. Modifications of the conventional sol-gel method, such as the
addition of surfactants, have been employed in synthetic procedures. Moreover,
hydrothermal, solvothermal, sonochemical and microwave methods have also been
used as alternative approaches. Recently, the use of ionic liquids represents a
burgeoning direction in inorganic material synthesis. Ionic liquids are
exceptional solvents consisting of ions possessing low vapor pressure and tunable
solvent properties. This article reviews the preparation of TiO2 materials using
ionic liquids with various synthetic approaches. Also, sustainable energy and
environmental cleanup applications of TiO2 materials, including the treatment of
hazardous organic substances and hydrogen energy derived from electrochemical
methods, are discussed.
PMID- 27483751
TI - A Comprehensive Review of Gas Sensors Using Carbon Materials.
AB - In recent years, interest in carbon materials for use in gas sensors has
increased. Carbon materials have unique electrical, optical and mechanical
properties, making these materials very interesting. In this review, the
properties of carbon materials are first introduced. Surface modification for
carbon materials, fabrication for gas sensors, and the gas-sensing conditions and
mechanisms according to the different types of carbon materials are chiefly
described. In particular, this review focuses on the enhancement of the gas
sensing properties of carbon materials depending on the modification methods used
and its mechanism.
PMID- 27483752
TI - Electrochemical Properties of Graphene Oxide/Resol Composites as Electrode
Materials for Supercapacitor Applications.
AB - RGO/Resol carbon composites were prepared from a mixture of reduced GO and a low
molecular-weight phenolic resin (Resol) solution. The effects of the calcination
temperature, amount of Resol added and KOH treatment on the electrochemical
performance of the RGO/Resol composites were investigated. The physical and
electrochemical properties of the composite materials were characterized by
scanning electron microscopy (SEM), X-ray diffraction (XRD), Brunauer, Emmett and
Teller (BET) surface areas measurements, and cyclic voltammetry (CV). The
relationships between their physical properties and their electrochemical
performance were examined for use as super-capacitors (SCs). The RGO/Resol
composite calcined at 400 degrees C after the KOH loading showed dramatically
improved electrochemical properties, showing a high BET surface and capacitance
of 2190 m2/g and 220 F/g, respectively. The RGO/Resol composites calcined after
the KOH treatment showed much better capacitor performance than those treated
only thermally at the same temperature without KOH impregnation. The fabrication
of high surface electrodes was essential for improving the SCs properties.
PMID- 27483753
TI - Dynamic Behavior of Nano-Size Dust Particles in a Magnetic Field Channel.
AB - Removal of very small dust from indoor public spaces, such as metro subway
stations, is a challenge. A large proportion of subway dust, particularly that of
submicron sizes, contains iron compounds. This study sought to understand the
dynamic behavior of such fine iron dust in a magnetic field. The computer aided
fluid dynamics (CFD) calculation revealed that the design and configuration of a
rectangular flow channel with magnets determine the dynamic motion of particles.
An attractive magnetic emitter arrangement produced higher magnetic flux density
than a repulsive arrangement. Additional ferromagnetic wire mesh inserted into
the duct channel could provide a more systematic magnetic field and collect more
dust. The field gradient for 0.3 mm thick wire was more than twice that of 0.5 mm
wire. The provision of a magnetic field could contribute a 20% increase in 100 nm
particle collection and an increase of 5% in 10 nm.
PMID- 27483754
TI - The Effect of K and Acidity of NiW-Loaded HY Zeolite Catalyst for Selective Ring
Opening of 1-Methylnaphthalene.
AB - Bi-functional catalysts were prepared using HY zeolites with various SiO2/Al2O3
ratios for acidic function, NiW for metallic function, and K for acidity control.
1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in
heavy oil, and its selective ring opening reaction was investigated using the
prepared bi-functional catalysts with different levels of acidity in a fixed bed
reactor system. In NiW/HY catalysts without K addition, the acidity decreased
with the SiO2/Al2O3 mole ratio of the HY zeolite. Ni1.1W1.1/HY(12) catalyst
showed the highest acidity but slightly lower yields for the selective ring
opening than Ni1.1W1.1/HY(30) catalyst. The acidity of the catalyst seemed to
play an important role as the active site for the selective ring opening of 1
methylnaphthalene but there should be some optimum catalyst acidity for the
reaction. Catalyst acidity could be controlled between Ni1.1W1.1/HY(12) and
Ni1.1W1.1/HY(30) by adding a moderate amount of K to Ni1.1W1.1/HY(12) catalyst.
K0.3Ni1.1W1.1/HY(12) catalyst should have the optimum acidity for the selective
ring opening. The addition of a moderate amount of K to the NiW/HY catalyst must
improve the catalytic performance due to the optimization of catalyst acidity.
PMID- 27483755
TI - Adsorption and Photocatalytic Degradation of Methylene Blue Using Potassium
Polytitanate and Solar Simulator.
AB - Solar photocatalytic degradation of organic water pollutants can be used to
degrade toxic organic pollutants in water. In this study, potassium titanate
nanofibres were synthesized by an aqueous peroxide route at high pH and examined
as photocatalysts for photodegradation of methylene blue (MB) using a solar
simulator. Initially, MB was adsorbed on the surface of potassium polytitanates
to achieve adsorption equilibrium before the photocatalysts were illuminated
using solar simulator. The results showed that potassium polytitanate nanofibres
were effective adsorbents of MB and also facilitated its photocatalytic
degradation. Sulphate ion evolution during photocatalysis confirmed that some
mineralisation occurred and hence photo-oxidative degradation of MB took place.
The optimum operational conditions for the photocatalytic degradation of MB were
found at 0.05 g/L of photocatalyst load, 10 mg/L MB and pH 7. The stability and
regeneration of the photocatalyst specimen was also studied for 3 degradation
cycles using adsorption/photocatalysis model. Morphological structure analysis of
potassium titanate showed nanocrystallines structure of longitudinally-oriented
isolated fibre with a length up to several micrometres with diameters ranging
from 10 to 20 nanometres.
PMID- 27483756
TI - Roles of Promoters in V2O5/TiO2 Catalysts for Selective Catalytic Reduction of
NOx with NH3: Effect of Order of Impregnation.
AB - Recently, various promoters for commercial selective catalytic reduction (SCR)
catalysts are used to improve DeNOx activity at low temperature. We aimed at
finding the optimum condition to prepare V2O5/TiO2 catalyst by changing promoters
(W, Ce, Zr and Mn), not only for improving SCR reactivity, but also for reducing
N2O formation at high temperature. In addition, we changed the order of
impregnation between promoter and vanadium precursors on TiO2 support and
observed its effect on activity and N2O selectivity. We utilized various
analytical techniques, such as N2 adsorption-desorption, X-ray Diffraction (XRD),
Raman spectroscopy, UV-visible Diffuse Reflectance Spectroscopy (UV-vis DRS) and
Temperature Programmed Reduction with hydrogen (H2-TPR) to investigate the
physicochemical properties of V2O5/TiO2 catalysts. It was found that W and Ce
added V2O5/TiO2 catalysts showed the most active DeNOx properties at low
temperature. Additionally, the difference in impregnation order affected the SCR
activity. The superiority of low temperature activity of the vanadium firstly
added catalysts (W or Ce/V/TiO2) is attributed to the formation of more
polymerized V2O5 on the sample.
PMID- 27483757
TI - Heterogeneous Electrocatalyst of Palladium-Cobalt-Phosphorus on Carbon Support
for Oxygen Reduction Reaction in High Temperature Proton Exchange Membrane Fuel
Cells.
AB - Palladium-cobalt-phosphorus (PdCoP) catalysts supported on carbon (Ketjen Black)
were investigated as a cathode catalyst for oxygen reduction reaction (ORR) in
high temperature proton exchange membrane fuel cells (HT-PEMFCs). The PdCoP
catalyst was synthesized via a modified polyol process in teflon-sealed reactor
by microwave-heating. From X-ray diffraction and transmission electron
microscopic analysis, the PdCoP catalyst exhibits a face-centered cubic
structure, similar to palladium (Pd), which is attributed to form a good solid
solution of Co atoms and P atoms in the Pd lattice. The PdCoP nanoparticles with
average diameter of 2.3 nm were uniformly distributed on the carbon support. The
electrochemical surface area (ECSA) and ORR activity of PdP, PdCo and PdCoP
catalysts were measured using a rotating disk electrode technique with cyclic
voltammetry and the linear sweep method. The PdCoP catalysts showed the highest
performances for ECSA and ORR, which might be attributed both to formation of
small nanoparticle by phosphorus atom and to change in lattice constant of Pd by
cobalt atom. Furthermore, The HT-PEMFCs single cell performance employing PdCoP
catalyst exhibited an enhanced cell performance compared to a single cell using
the PdP and PdCo catalysts. This result indicates the importance of electric and
geometric control of Pd alloy nanoparticles that can improve the catalytic
activity. This synergistic combination of Co and P with Pd could provide the
direction of development of non-Pt catalyst for fuel cell system.
PMID- 27483758
TI - Effectiveness of Modal Decomposition for Tapping Atomic Force Microscopy
Microcantilevers in Liquid Environment.
AB - The modal decomposition of tapping mode atomic force microscopy microcantilevers
in liquid environments was studied experimentally. Microcantilevers with
different lengths and stiffnesses and two sample surfaces with different elastic
moduli were used in the experiment. The response modes of the microcantilevers
were extracted as proper orthogonal modes through proper orthogonal
decomposition. Smooth orthogonal decomposition was used to estimate the resonance
frequency directly. The effects of the tapping setpoint and the elastic modulus
of the sample under test were examined in terms of their multi-mode responses
with proper orthogonal modes, proper orthogonal values, smooth orthogonal modes
and smooth orthogonal values. Regardless of the stiffness of the microcantilever
under test, the first mode was dominant in tapping mode atomic force microscopy
under normal operating conditions. However, at lower tapping setpoints, the
flexible microcantilever showed modal distortion and noise near the tip when
tapping on a hard sample. The stiff microcantilever had a higher mode effect on a
soft sample at lower tapping setpoints. Modal decomposition for tapping mode
atomic force microscopy can thus be used to estimate the characteristics of
samples in liquid environments.
PMID- 27483759
TI - Physico-Chemical Property and Catalytic Activity of a CeO2-Doped MnO(x)-TiO2
Catalyst with SO2 Resistance for Low-Temperature NH3-SCR of NO(x).
AB - The effects of CeO2 addition on the catalytic activity and the SO2 resistance of
CeO2-doped MnO(x)-TiO2 catalysts were investigated for the low-temperature
selective catalytic reduction (SCR) with NH3 of NO(x) emissions in marine
applications. The most active catalyst was obtained from 30 wt% CeO2-MnO(x)-TiO2
catalyst in the whole temperature range of 100-300 degrees C at a low gas hourly
space velocity (GHSV) of 10,000 h(-)1, and its de-NO(x) efficiency was higher
than 90% over 250 degrees C. The enhanced catalytic activity may contribute to
the dispersion state and catalytic acidity on the catalyst surface, and the
highly dispersed Mn and Ce on the nano-scaled TiO2 catalyst affects the increase
of Lewis and Bronsted acid sites. A CeO2-rich additive on MnO(x)-TiO2 could
provide stronger catalytic acid sites, associated with NH3 adsorption and the SCR
performance. As the results of sulfur resistance in flue gas that contains SO2,
the de-NO(x) efficiency of MnO(x)-TiO2 decreased by 15% over 200 degrees C,
whereas that of 30 wt% ceria-doped catalyst increased by 14-21% over 150 degrees
C. The high SO2 resistance of CeO2-MnO(x)-TiO2 catalysts that resulted from the
addition of ceria suppressed the formation of Mn sulfate species, which led to
deactivation on the surface of nano-catalyst.
PMID- 27483760
TI - Aromatization of Ethanol Over Desilicated ZSM-5 Zeolites: Effect of Pore Size in
the Mesoporous Region.
AB - Mesoporous ZSM-5 zeolites were obtained from microporous ZSM-5 by desilication
using aqueous NaOH solutions, and their catalytic activity in the aromatization
of ethanol was investigated in order to understand the effects of pore size, in
the mesoporous region, on the product distribution and stability of the
catalysts. Mesopores generally enhanced the selectivities towards aromatics and
stability for aromatization. Mesopores with a maximum pore diameter of around 13
nm were the most effective in the aromatization process (especially for benzene
and toluene), suggesting that pore-diameter optimization is necessary for
efficient catalysis such as aromatization.
PMID- 27483761
TI - Effect of Gold Particle Size on Steam Reforming of Methanol Over Au/CeO2-ZrO2
Catalysts.
AB - We examined the effect of the particle size of gold on steam reforming of
methanol over Au/CeO2-ZrO2 catalysts. Gold was loaded onto CeO2-ZrO2 through
deposition-precipitation. The average particle size (2-12 nm) of the gold was
controlled by thermal reduction under H2 at various temperatures and by chemical
reduction with various reducing agents. The catalytic activity decreased
significantly with increasing particle size of the gold. The turnover frequency
at the interface between gold and a support appeared to be independent of
particle size in the range 2-5 nm, which implies that the perimeter of the
particle may be the active site for this reaction. Methanol adsorption and
conversion over these catalysts were also investigated with in-situ diffuse
reflectance infrared Fourier transform spectroscopy. Analytical results for
various adsorbed intermediate species during methanol conversion suggests that
transformation of methoxy species is facilitated by use of smaller gold
particles.
PMID- 27483762
TI - Stabilization of Hydrogen Production via Methanol Steam Reforming in Microreactor
by Al2O3 Nano-Film Enhanced Catalyst Adhesion.
AB - In hydrogen production by methanol steam reforming reaction with microchannel
reactor, Al2O3 thin film formed by atomic layer deposition (ALD) was introduced
on the surface of microchannel reactor prior to the coating of catalyst
particles. Methanol conversion rate and hydrogen production rate, increased in
the presence of Al2O3 thin film. Over-view and cross-sectional scanning electron
microscopy study showed that the adhesion between catalyst particles and the
surface of microchannel reactor enhanced due to the presence of Al2O3 thin film.
The improvement of hydrogen production rate inside the channels of microreactor
mainly came from the stable fixation of catalyst particles on the surface of
microchannels.
PMID- 27483763
TI - Low Frequency Ultrasonication of Degussa P25 TiO2 and Its Superior Photocatalytic
Properties.
AB - We report the simple and effective method for enhancing the photocatalytic
properties of Degussa P25 TiO2 by low frequency ultrasonication. The improvement
in the crystallinity of ultrasonicated TiO2 was confirmed by the X-ray
diffraction and Raman spectroscopy studies. Further, the X-ray photoelectron
spectroscopy was utilized to study the changes in chemical nature and band edge
due to the effect of ultrasonication and H2O2 solvent. The transmission electron
microscope (TEM) was used to analysis the surface distortion. The Moire fringes
in TEM were examined to understand the partial transformation of amorphous to
crystalline anatase structure and overlapping of rutile over anatase crystal. The
photocatalytic results indicated improvement in the degradation of methylene blue
dye. The degradation efficiency was estimated to be 86% for ultrasonicated TiO2,
which is higher as compared to 40% of P25. The rate constant values revealed four
times superior degradation property of ultrasonicated TiO2. The improvement in
the photocatalytic efficiency was correlated to the formation of rutile/anatase
TiO2 aggregation and its consequences on electron-hole recombination.
PMID- 27483764
TI - Electro-Catalytic Activity of RuO2-IrO2-Ta2O5 Mixed Metal Oxide Prepared by Spray
Thermal Decomposition for Alkaline Water Electrolysis.
AB - Oxygen evolution reaction for alkaline water electrolysis was studied using
various mixed metal oxide catalysts. Mixed metal oxide electrodes consisting of
RuO2, IrO2, and Ta2O5 with various ratios on a titanium substrate were prepared
by spray thermal decomposition. The crystallinity of the synthesized catalyst was
investigated via X-ray diffraction, and the oxidation state of each component was
determined using X-ray photoelectron spectroscopy (XPS). Surface morphology was
investigated by scanning electron microscopy, and the roughness factor was
determined by cyclic voltammetry (CV) in 1 M H2SO4. Electo-catalytic activity for
oxygen evolution reaction was measured by cyclic voltammetry (CV) in 1 M KOH at
room temperature, and it was found to be strongly dependent.on composition of
catalyst. Among all electrodes tested, catalyst with a composition of Ru:Ir:Ta =
1:2:2.5 exhibited the highest current density of 100 mA cm(-2) at 1.67 V,
corresponding to an overpotential of 0.44 V.
PMID- 27483765
TI - Sulfation and Desulfation Behavior of Pt-BaO/MgO-Al2O3 NOx Storage Reduction
Catalyst.
AB - The comparative study between Pt-BaO/Al2O3 and Pt-BaO/MgO-Al2O3 gives the
information about the effect of MgO addition to Al2O3 support on the sulfation
and desulfation behavior of Pt-BaO/MgO-Al2O3 NOx storage reduction catalyst. The
sulfated two samples were analyzed by using element analysis (EA), X-ray
diffraction (XRD), H2 temperature programmed reaction (H2 TPRX) and NOx uptake
measurement. The amount of sulfur uptake on 2 wt% Pt-20 wt% BaO/Al2O3 and 2 wt%
Pt-20 wt% BaO/MgO-Al2O3 are almost identical as 0.45 and 0.40 of S/Ba,
respectively, which yields the drastic decrease in NOx uptake for both sulfated
samples. However, after desulfa- tion with H2 at 600 degrees C, the residual
sulfur amount on MgO-Al2O3 supported catalyst is three times larger than that on
Al2O3 supported one, indicating that sulfur species formed on the former are more
stable than those on the latter. It is also well corresponding to the H2 TPRX
results where the main H2S peak from MgO-Al2O3 supported sample is observed at
higher temperature than Al2O3 supported one, resulting in the lower NOx uptake
activity of former sample than the latter one. Meanwhile, after desulfation of
MgO-Al2O3 supported sample at 700 degrees C and 800 degrees C, the activity is
recovered more significantly due to the removal of the large amount of sulfur
while Al2O3 supported one decreases monotonically due to the sintering of Pt
crystallite and the formation of BaAl2O4 phase. It is summarized that MgO-Al2O3
supported catalyst enhances the thermal stability of the catalyst, however, forms
the stable sulfate species, which needs to be improved to develop the more sulfur
resistant NSR catalyst system.
PMID- 27483766
TI - Morphology Control of Zinc Oxide Nanostructure on Single Layer Graphene.
AB - Various morphologies of zinc oxide (ZnO) nanostructures on single layer graphene
were synthesized by electrodeposition method. The current density was utilized to
control the morphology of the ZnO. The Scanning Electron Microscope (SEM) was
used to examine the surface morphology of the samples. SEM analysis shows
morphology changes to nanorod, flower, and flakes with increase in the current
density from 0.1, 0.2, and 0.3 mA/cm(-1) respectively. The XRD, XPS, and Raman
spectroscopy were adopted to characterize the ZnO nanostructure and to understand
the formation of various morphologies. The Raman result clearly shows extra modes
due to for flakes structure caused by c-axis orientation along the substrate
direction. Further, XPS data also supports formation of ZnO without any other
intermediate compound such as Zn(OH)2. The formation of various morphologies was
correlated to the formation different ratio of Zn2+ and OH- ions and the change
in growth direction due to various current densities.
PMID- 27483767
TI - Contact Force Compensated Thermal Stimulators for Holistic Haptic Interfaces.
AB - We present a contact force compensated thermal stimulator that can provide a
consistent tempera- ture sensation on the human skin independent of the contact
force between the thermal stimulator and the skin. Previous passive thermal
stimulators were not capable of providing a consistent tem- perature on the human
skin even when using identical heat source voltage due to an inconsistency of the
heat conduction, which changes due to the force-dependent thermal contact
resistance. We propose a force-based feedback method that monitors the contact
force and controls the heat source voltage according to this contact force, thus
providing consistent temperature on the skin. We composed a heat circuit model
equivalent to the skin heat-transfer rate as it is changed by the contact forces;
we obtained the optimal voltage condition for the constant skin heat-transfer
rate independent of the contact force using a numerical estimation simulation
tool. Then, in the experiment, we heated real human skin at the obtained heat
source voltage condition, and investigated the skin heat transfer-rate by
measuring the skin temperature at various times at different levels of contact
force. In the numerical estimation results, the skin heat-transfer rate for the
contact forces showed a linear profile in the contact force range of 1-3 N; from
this profile we obtained the voltage equation for heat source control. In the
experimental study, we adjusted the heat source voltage according to the contact
force based on the obtained equation. As a result, without the heat source
voltage control for the contact forces, the coefficients of variation (CV) of the
skin heat-transfer rate in the contact force range of 1-3 N was found to be
11.9%. On the other hand, with the heat source voltage control for the contact
forces, the CV of the skin heat-transfer rate in the contact force range of 1-3 N
was found to be barely 2.0%, which indicate an 83.2% improvement in consistency
compared to the skin heat-transfer rate without the heat source voltage control.
The present technique provides a consistent temperature sensation on the human
skin independent of the body movement environment; therefore, it has high
potential for use in holistic haptic interfaces that have thermal displays.
PMID- 27483768
TI - Quantitative Assessment of Friction Characteristics of Single-Layer MoS2 and
Graphene Using Atomic Force Microscopy.
AB - Atomically thin layered materials such as MoS2 and graphene have attracted a lot
of interest as protective coating layers for micro- and nano-electromechanical
devices based on their superior mechanical properties and chemical inertness. In
this work, the frictional characteristics of single layer MoS2 and graphene
prepared by the mechanical exfoliation method were quantitatively investigated
using atomic force microscopy. The results showed that both MoS2 and graphene
exhibited relatively low friction forces of 1-3 nN under normal forces ranging
from 1 to 30 nN. However, a higher increase in the friction force as the normal
force increased was observed in the case of MoS2. The differences in the adhesion
characteristics and mechanical properties of atomically thin layered materials
may influence the puckering of the layer, which in turn influences the frictional
behavior.
PMID- 27483769
TI - Catalytic Reforming of Lignin-Derived Bio-Oil Over a Nanoporous Molecular Sieve
Silicoaluminophosphate-11.
AB - Catalytic pyrolysis of lignin, a major constituent of biomass, was performed. A
nanoporous molecular sieve silicoaluminophosphate-11 (SAPO-11) was selected as
catalyst. Thermogravimetric analysis showed that 500 degrees C was the optimal
pyrolysis temperature. Pyrolyzer-gas chromatography/mass spectroscopy was used to
investigate the pyrolysis product distribution. Production of phenolics, the
dominant product from the pyrolysis of lignin, was promoted by the increase in
the catalyst dose. In particular, low-molecular-mass phenolics were produced more
over SAPO-11, while high-molecular-mass phenolics and double-bond-containing
phenolics were produced less. The fraction of aromatic compounds, including
benzene, toluene, xylene, and ethylbenzene, was also increased by catalytic
reforming. The catalytic effects were more pronounced when the catalyst/biomass
ratio was increased. The enhanced production of aromatic compounds by an acidic
catalyst obtained in this study is in good agreement with the results of previous
studies.
PMID- 27483770
TI - Effects of Porous Carbon Cathode Additives on the Electrochemical Performance of
Li-S Cells.
AB - In this paper, the effects of porous carbon additives, which included
microporous, mesoporous and macroporous carbon, on the electrochemical properties
of a sulfur cathode were examined. The type of carbon additive significantly
affected the initial capacity reduction, though it did not affect the cycling
stability of the sulfur cathodes. The cathodes that incorporated mesoporous and
macroporous carbon additives delivered much higher initial capacities of -970 and
-900 mAh/g, respectively, compared with those (-715 mAh/g) with graphite and
microporous carbon additives. The EDS results showed that these features are
strongly related to the absorption characteristics of the carbon additives.
Importantly, it was found that the macroporous carbons with a pore size of -65 nm
effectively confined dissolved polysulfides. Interestingly, the sulfur cathodes
with microporous carbon additives exhibited extremely similar electrochemical
behavior to those with nonporous graphite, which suggests that activated carbon
particles do not serve as polysulfide reservoirs during discharge.
PMID- 27483771
TI - Green Synthesis of Metal Nanoparticles Using Sprout Plants: Pros and Cons.
AB - A critical need in the field of nanotechnology is the development of a
sustainable and eco-friendly process for the synthesis of metallic nanoparticles
(NPs). To accomplish this, the use of live plants becomes essential for the
production of low-cost, energy-efficient, and nontoxic metallic NPs. In this
study, we tried in-vivo synthesis (green synthesis) of silver and gold NPs using
seeds of bean, radish, and alfalfa, which were grown hydroponically in aqueous
solutions containing metal salts, 20-25 nm sized NPs were found on the inner
surfaces of the plants' vascular cylinders and cortex. The amounts of NPs taken
up by the intracellular systems were clearly dependent on the exposure time and
concentration of the metal salts. Although these results regarding the green
synthesis of NPs on the growth of plant species are somewhat interesting and
effective, metal salts adversely affected the root growth of the plants. Silver
ions in the growth media showed a more negative impact on root growth compared to
gold ions. Therefore, even though biosynthesis of metal NPs using live plants is
considered as green synthesis, we have to consider their phytotoxicity on plant
growth.
PMID- 27483772
TI - Characterization on the Expanding Nature of Graphite in Microwave-Irradiated
Exfoliation.
AB - Much still remains uncertain and controversial about the mechanophysical
parameters involved in graphite exfoliation. Here, we quantify the expansion
characteristics of natural graphite in the microwave-irradiated exfoliation where
KMnO4 and HNO3 are used as an oxidant and an intercalant, respectively. As a mark
of the degree to which graphite becomes exfoliated, the expansion ratio of
graphite is investigated as a function of mix ratio by weight of 3 ingredients
(i.e., graphite, KMnO4, and HNO3), mixing time, and graphite physical properties.
The findings of this study will lead to a better understanding of graphite
exfoliation and make it possible to achieve the industrial-scale production of
defect-free graphene.
PMID- 27483773
TI - Inhibitory Effects of Silver Nanoparticles on Removal of Organic Pollutants and
Sulfate in an Anaerobic Biological Wastewater Treatment Process.
AB - The increasing use of silver nanoparticles (AgNPs) in commercial products and
industrial processes raises issues regarding the toxicity of sludge biomass in
biological wastewater treatment plants, due to potential antimicrobial
properties. This study investigated the effects of AgNPs on removal of organic
pollutants and sulfate in an anaerobic biological sulfate reduction process. At
AgNPs concentrations of up to 10 mg/L, no significant inhibition of sulfate and
COD removal was observed. However, at higher concentrations (50-200 mg/L) sulfate
and COD removal efficiencies were significantly decreased to 51.8% and 33.6%,
respectively. Sulfate and COD reduction followed first-order kinetics at AgNPs
concentrations of up to 10 mg/L and second-order kinetics at AgNPs concentrations
of 50-200 mg/L. Lactate dehydrogenase release profiles showed increases in
cytotoxicity at AgNPs concentrations greater than 50 mg/L suggesting cell
membrane disruption. Analysis of extracellular polymeric substances (EPS) from
sulfidogenic sludge biomass and of Fourier transform infrared (FT-IR) spectra
showed a decrease in concentrations of carbohydrates, proteins, humic substances,
and lipids in the presence of AgNPs. Moreover, the interaction of AgNPs with
sludge biomass and the damage caused to cell walls were confirmed through
scanning electron microscopy with energy dispersive X-ray spectroscopy.
PMID- 27483774
TI - Formation of RNA Beads from Various DNA Nanoring Structures.
AB - By taking advantages of rolling circle transcription, one of the powerful methods
to overcome the instability of RNA, we successfully synthesized RNA particles
having high copy numbers of RNA strands. To examine dependence of RNA particle
formation to template circular DNA strands, we synthesized RNA beads with 65-nt,
92-nt and 200-nt DNA nanoring structures as template circular DNA. Our conclusion
is that characteristics of RNA beads could be controlled with various template
circular DNA for RCT. It is feasible that our RNA beads could be used for RNAzyme
based metal sensors such as aqueous lead ion sensing. In this case, we expect
that multi-metal ion detection would be possible by using 200-nt circular DNA
bearing multiple desired functions as a template for RNA bead formation.
Furthermore, certain features of RNA beads such as sensitivity to nuclease
digestion and maximum loading amount of drugs when used as a carrier are expected
to be further adjusted by choosing appropriate porosity and size.
PMID- 27483775
TI - Effective Removal of Heavy Metals from Wastewater Using Modified Clay.
AB - We report an economical and eco-friendly way to remove the heavy metal pollutant
using modified clay. The modification of clay was done by calcining the natural
clay from Kyushu region in Japan. Further, the removal efficiency for various pH
and contact time was evaluated. The morphology of the clays was studied using the
scanning electron microscopy (SEM). The structural and chemical analyses of
modified clay were done by using X-ray diffraction (XRD), Raman spectroscopy, and
Energy dispersion analysis (EDAX) to understand the properties related to the
removal of heavy metal pollutant. Further, we studied the absorption efficiency
of clay for various pH and contacting time using Ni polluted water. The modified
clays show better removal efficiency for all pH with different saturation time.
The adsorption follows pseudo-second order kinetics and the adsorption capacity
of modified clay is 1.5 times larger than that of natural clay. The increase in
the adsorption efficiency of modified clay was correlated to the increase in
hematite phase along with increase in surface area due to surface morphological
changes.
PMID- 27483776
TI - Surface-Energetic Heterogeneity of Nanoporous Solids for CO2 and CO Adsorption:
The Key to an Adsorption Capacity and Selectivity at Low Pressures.
AB - This study has been focused on surface energetic heterogeneity of zeolite (H
mordenite, "HM"), activated carbon ("RB2") and metal-organic framework family
("Z1200") materials and their isotherm features in adsorption of CO2 and CO at 25
degrees C and low pressures <= 850 Torr. The nanoporous solids showed not only
distinctive shape of adsorption isotherms for CO2 with relatively high
polarizability and quadrupole moment but also different capacities in the CO2
adsorption. These differences between the adsorbents could be well correlated
with their surface nonuniformity. The most heterogeneous surfaces were found with
the HM that gave the highest CO2 uptake at all pressures allowed, while the Z1200
consisted of completely homogeneous surfaces and even CO2 adsorption linearly
increased with pressure. An intermediate character was indicated on the surface
of RB2 and thus this sorbent possessed isotherm features between the HM and Z1200
in CO2 adsorption. Such different surface energetics was fairly consistent with
changes in CO2/CO selectivity on the nanoporous adsorbents up to equilibrated
pressures near 850 Torr.
PMID- 27483777
TI - Conversion of Acetic Acid from the Catalytic Pyrolysis of Xylan Over CeO2.
AB - CeO2 was synthesized hydrothermally in supercritical water and applied to the
catalytic pyrolysis of xylan. Acetic acid, which is the main component in bio-oil
produced from the non-catalytic pyrolysis of xylan, deteriorates the fuel quality
of the oil. Catalysis over CeO2 effectively converted the acetic acid to ketone
species, such as acetone, thereby reducing the acidity of the oil considerably.
The content of aromatics in bio-oil was also increased substantially by
catalysis.
PMID- 27483778
TI - Facile Synthesis of Iron Oxide/Graphene Nanocomposites Using Liquid Phase Plasma
Method.
AB - Liquid phase plasma (LPP) method was applied, for the first time, to the
impregnation of iron oxide nanoparticles onto graphene sheet. Iron oxide
nanoparticles with the size of 50 nm were precipitated with uniform dispersion on
the surface of graphene sheet. The amount of iron oxide nanoparticles
precipitated on graphene sheets increased with increasing LPP process times. The
XPS, Raman and EDX analyses showed that the iron oxide/graphene composites
synthesized by the LPP process.
PMID- 27483779
TI - Aerosol-Processed Nanomaterials for Antimicrobial Air Filtration.
AB - Health-care products are a dominant application of various nanotechnologies.
Silver nanoparticles are widely used in commercial products requiring
antimicrobial activity. Due to the limitations of wet processing in
nanotechnology applications, dry aerosol processes have been developed for indoor
antimicrobial air filtration. In this work, various aerosol processes for the
synthesis or generation of nanomaterials, natural-product nanoparticles, and
hybrid nanoparticles are reviewed. Key aerosol processes and the morphologies of
various antimicrobial nanoparticles generated using a variety of systems or
deposited on filter fibers are introduced.
PMID- 27483780
TI - Application of Silver and Silver Oxide Nanoparticles Impregnated on Activated
Carbon to the Degradation of Bromate.
AB - Silver and silver oxide nanoparticles were impregnated on the surface of powdered
activated carbon (PAC) using a single-step liquid phase plasma (LPP) method.
Spherical silver and silver oxide nanoparticles of 20 to 100 nm size were
dipersed evenly on the surface of PAC. The impregnated PAC exhibited a higher
activity for the decomposition of bromate than bare PAC. The XPS, Raman and EDX
analyses showed that the Ag/PAC composites synthesized by the LPP process.
PMID- 27483781
TI - Facile Synthesis of F-TiO2/TiOF2 Mixture by High-Thermal Direct Fluorination and
Its Photocatalytic Evaluation.
AB - In this study, the mixture of F-TiO2/TiOF2 has been easily synthesized using
titanium (IV) isopropoxide (TTIP) as titanium source by direct fluorination at
high temperature according to different partial pressure of fluorine gas. The
morphological properties and crystalline of thermally fluorinated photocatalysts
were investigated using scanning electron microscope (SEM) and X-ray diffraction
(XRD). Chemical composition and optical properties of thermally fluorinated
photocatalysts were analyzed by X-ray Photoelectron Spectroscopy (XPS) and
Photoluminescence (PL) spectrometer. The phase of F-TiO2/TiOF2 mixture was
generated with different proportion by high-thermal direct fluorination. With the
increase of the fluorine partial pressure, the proportion of cubic-shaped TiOF2
increased in comparison with globular-shaped TiO2. Also, the degradation rate
constant of thermally fluorinated photocatalysts exhibited approximately 70 times
more than that of TiO2, which were not treated fluorine gas. It is attributable
to the increase of the surface hydroxyl group content and oxygen vacancies.
PMID- 27483782
TI - Synthesis and Characterisation of Porous Titania-Silica Composite Aerogel for
NO(x) and Acetaldehyde Removal.
AB - In this study, the synthesis of porous titania-silica (TiO2-SiO2) composite
aerogel at ambient pressure by using non-hazardous chemicals as a source of
silica was investigated. TiO2-SiO2 composite aerogels were characterised and
their photocatalytic performances were investigated for the removal efficiency of
acetaldehyde and NO(x) under UV light. Results showed that porous composite
aerogel with aggregated morphology, high surface area and an increased
mesoporosity were formed. TiO2-SiO2(1.8) composite, with high Ti/Si ratio, showed
the best results in terms of photocatalytic removal of acetaldehyde and nitrogen
oxide.
PMID- 27483783
TI - Synthesis of Dicyclopentadiene Oligomer Over Nanoporous Al-MCM-41 Catalysts.
AB - One step reaction composed of DCPD oligomerization and DCPD oligomer
isomerization was investigated over nanoporous Al-MCM-41 catalysts. The effects
of aluminum grafting over MCM-41 on the catalyst characteristics were studied
with respect to the synthesis of TCPD isomer. Physical and chemical properties of
the catalysts were analyzed by N2 adsorption, temperature-programmed desorption
of ammonia, and infrared spectroscopy of adsorbed pyridine. The overall number of
acid sites as well as the number of Lewis acid sites increased with increasing of
aluminum content over MCM-41. When utilizing MCM-41 and Al-MCM-41 as the
catalyst, DCPD oligomerization reaction activity greatly increased compared to
the thermal reaction. The highest TCPD isomer selectivity over the Al-MCM-41
catalyst with the highest aluminum content could be ascribed to the largest
amount of acid sites. This study showed an increased level of TCPD isomer
selectivity by an increasing level of Lewis acid sites through aluminum addition
over MCM-41.
PMID- 27483784
TI - The Study on the Performance of Carbon Supported PtSnM (M = W, Pd, and Ni)
Ternary Electro-Catalysts for Ethanol Electro-Oxidation Reaction.
AB - PtSn/C and Pt5Sn4M/C (M = W, Pd, Ni) electrocatalysts were prepared by
impregnation method using NaBH4 as a reducing agent. Chemical composition,
crystalline size, and alloy formation were determined by EDX, XRD and TEM. The
average particle sizes of the synthesized catalysts were approximately 3.64-4.95
nm. The electro-chemical properties were measured by CO stripping, cyclic
voltammetry, linear sweep voltammetry, and chronoamperometry. The maximum
specific activity of the electro-catalysts for ethanol electro-oxidation was
406.08 mA m(-2) in Pt5Sn4Pd/C. The poisoning rate of the Pt5Sn4Pd/C (0.0017% s(
1)) was 4.5 times lower than that of the PtSn/C (0.0076% s(-1)).
PMID- 27483785
TI - Mn(2+)-Ion Site Distribution of Zeolite Y (FAU, Si/Al = 1.56) Depending on the
Ion-Exchange Ratio.
AB - To investigate the tendency of Mn(2+)-ion exchange into zeolite Y, four single
crystals of fully dehydrated Mn2+, Na(+)-exchanged zeolite Y (Si/Al = 1.56) were
prepared by the exchange of Na75-Y (INa75I[Si117Al75,O384]-FAU) with aqueous of
various concentrations by Mn2+ and Na+ in a total 0.05 M for molar ratios of 1:1
(crystal 1), 1:25 (crystal 2), 1:50 (crystal 3), and 1:100 (crystal 4),
respectively, followed by vacuum dehydration at 400 degrees C. Their single
crystal structures were determined by synchrotron X-ray diffraction techniques in
the cubic space group Fd3(-)m and were refined to the final error indices R1/wR2
= 0.0440/0.1545, 0.0369/0.1153, 0.0373/0.1091, and 0.0506/0.1667, respectively.
Their unit-cell formulas are approximately LMn33.5Na8I[Si117Al75O384]-FAU,
IMn20.5Na34I[Si117Al75O384]-FAU, IMn20.5Na34I[Si117Al75O384]-FAU, and
IMn16.5Na42I[Si117Al75O384]-FAU, respectively. The degree of Mn2+-ion exchange
increases from 44.3% to 89.1% with increasing the initial Mn2+ concentrations as
Na+ content and the unit cell constant of the zeolite framework decrease.
PMID- 27483786
TI - Synthesis of Hybrid Reduced Graphene Oxide Decorated with Ru(bpy)3(2+)-Doped
Silica Nanoparticles.
AB - Hybrid materials consisting of electrically conductive reduced graphene oxide
(RGO) and Ru(bpy)3(2+)-doped silica (Ru@SiO2) nanoparticles were synthesized by
hydrolysis of TEOS in the presence of Ru(bpy)3Cl2 and RGO. Many spherical Ru@SiO2
nanoparticles, of an average size of 96 nm, were observed to be strongly anchored
on a planar RGO surface in SEM and TEM images. FTIR and EDS analyses confirmed
the chemical compositions and functional groups of Ru@SiO2 and partially reduced
RGO. The RGO prepared by 200 degrees C thermal treatment of GO in N2 was probed
to have a multilayered sheet structure by XRD. An absorption spectrum of the
hybrid exhibited a considerable red-shift in the characteristic visible peak of
free Ru(bpy)3(2+) centered at 452 nm due to electrostatic interactions between
Ru(bpy)3(2+) and negatively charged silica, indicating strong immobilization of
Ru(bpy)3(2+) in the silica matrix.
PMID- 27483787
TI - L-Lactide Ring-Opening Polymerization with Tris(acetylacetonate)Titanium(IV) for
Renewable Material.
AB - A new Ti-type of catalyst for L-lactide polymerization was synthesized by
reaction of titanium(IV) isopropoxide (TTIP) with acetylacetone (AA). Moreover,
PLA was prepared by the bulk ring-opening polymerization using synthesized Ti
catalyst. Polymerization behaviors were examined depending on monomer/catalyst
molar ratio, polymerization temperature and time. The structure of synthesized
catalysts was verified with FT-IR and 1H NMR and the properties of poly(L
lactide) (PLLA) were examined by GPC, DSC and FT-IR. There existed about 30
minutes of induction time at the monomer/catalyst molar ratio of 300. The
molecular weight (MW) increased as monomer/catalyst molar ratio increased. The MW
increased almost linearly as polymerization progressed. Increasing polymerization
temperature increased the molecular weight of PLLA as well as monomer/catalyst
molar ratio. The melting point (T(m)) of polymers was in the range of 142 to 167
degrees C. Lower T(m) was expected to be resulted from relatively lower molecular
weight.
PMID- 27483788
TI - Heterogeneous Decomposition of Volatile Organic Compounds by Visible-Light
Activated N, C, S-Embedded Titania.
AB - In this study, a N-, C-, and S-doped titania (NCS-TiO2) composite was prepared by
combining the titanium precursor with a single dopant source, and the
photocatalytic activity of this system for the decomposition of volatile organic
compounds (VOCs) at indoor-concentration levels, under exposure to visible light,
was examined. The NCS-TiO2 composite and the pure TiO2 photocatalyst, used as a
reference, were characterized via X-ray diffraction, scanning electron
microscopy, ultraviolet-visible diffuse reflectance spectroscopy, X-ray
photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The
average efficiencies of benzene, toluene, ethyl benzene, and o-xylene
decomposition using NCS-TiO2 for were 70, 87, -100, and -100%, respectively,
whereas the values obtained using the pure TiO2 powder were -0, 18, 49, and 51%,
respectively. These results suggested that, for the photocatalytic decomposition
of toxic VOCs under visible-light exposure conditions, NCS-TiO2 was superior to
the reference photocatalyst. The decomposition efficiencies of the target VOCs
were inversely related to the initial concentration and relative humidity as well
as to the air-flow rate. The decomposition efficiencies of the target chemicals
achieved with a conventional lamp/NCS-TiO2 system were higher than those achieved
with a light emitting diode/NCS-TiO2 system. Overall, NCS-TiO2 can be used for
the efficient decomposition of VOCs under visible-light exposure, if the
operational conditions are optimized.
PMID- 27483789
TI - Evaluation of Cytotoxicity and Hypoxic Effect of Nitroimidazole Embedded
Nanoparticles.
AB - Adenylate cyclase is a key intracellular enzyme involved in energy imbalance
leading to tumor hypoxia and cytotoxicity. In this study, adenylate cyclase
activities in isolated hepatocytes and Kupffer cells were compared in the
presence of several metabolic stimulators. In cultured hepatocyte cells,
adenylate cyclase was stimulated by guanylyl imidotriphosphate (GITP), guanosine
triphosphate (GTP), progesterone and nitroimidazole embedded nanoparticle (NNP)
effectors, while prostaglandin E2 and F2alpha were used as effectors in cultured
Kupffer cells. The results showed that NNPs decreased adenylate cyclase specific
activity in a dose-dependent manner after preincubation of hepatocytes with NNPs.
The NNPs stimulated adenylate cyclase activities in hepatocytes were evaluated
based on measurement of cyclic adenosine monophosphate (cAMP). The stimulatory
effects of NNPs on adenylate cyclase were independent of the presence of GTP and
may have been due to a direct effect on the catalytic subunit of adenylate
cyclase. In addition, basal cAMP generation in hepatocyte cells was efficiently
suppressed by the NNPs. In conclusion, NNPs exerted direct effects on the
catalytic subunit of the adenylate cyclase system, and adenylate cyclase was
hormone sensitive in liver cells.
PMID- 27483790
TI - Catalytic Fast Pyrolysis of Wild Reed Over Nanoporous SBA-15 Catalysts.
AB - Wild reed was pyrolyzed over two nanoporous SBA-15 catalysts with different acid
characteristics: Si-SBA-15 and Al-SBA-15. Al was grafted on Si-SBA-15 to increase
the acidity and enhance the catalytic activity. Fast pyrolysis was carried out
using a pyrolysis-gas chromatography/mass spectrometry system at 550 degrees C
for real-time analysis of the products. Significant improvement of the product
bio-oil quality was attained by catalytic reforming over nanoporous Al-SBA-15.
The fraction of total oxygenates was reduced because of the decrease in. the
fraction of ketones, aldehydes, and carboxylates, which deteriorate the fuel
quality of bio-oil. On the other hand, the fractions of furans and aromatics,
which are the chemicals with high value-added, were increased by the catalytic
reforming. The catalytic activity of Al-SBA-15 was considerably higher than that
of Si-SBA-15 because the incorporation of Al increased the catalyst acidity.
PMID- 27483791
TI - Highly Dispersed Pt Nanoparticles for the Production of Aromatic Hydrocarbons by
the Catalytic Degrading of Alkali Lignin.
AB - Aromatic hydrocarbons were produced from lignin, a complex natural amorphous
polymer commonly regarded as by-product of the pulping process and from biofuel
production. The catalytic decomposition of lignin using supported Pt catalysts
was performed to produce small molecule hydrocarbons. Aromatic small-molecule
hydrocarbon products were identified and quantified using GC/MS and GC-FID, which
demonstrated that 27.6% of aromatic hydrocarbons were obtained from the activated
carbon-supported Pt (Pt/AC) catalyst which had the highest Pt surface area.
PMID- 27483792
TI - Catalytic Depolymerization of Alkali Lignin Using Supported Pt Nanoparticle
Catalysts.
AB - Alkali lignin, a byproduct of the pulping process, was depolymerized using Pt
nanoparticle catalysts. A depolymerized lignin with a lower molecular weight was
obtained and characterized with GPC and NMR. 31P-NMR using OH-sensitive probing
molecules showed the formation of guaiacyl OHs during the reaction, indicating
the cleavage of guaiacyl ether bonds.
PMID- 27483793
TI - Complete Oxidation of Benzene Over CuO-CeO2 Catalysts Prepared Using Different
Process.
AB - Catalytic combustion of benzene over CuO-CeO2 mixed oxides has been investigated.
The CuO-CeO2 mixed oxides were prepared using various methods and characterized
by XRD, BET and TPR. For the CuO-CeO2 catalysts with a Cu/(Cu + Ce) molar ratio
of more than 0.5, highly dispersed copper oxide species were shown at 2theta =
35.5 degrees and 38.8 degrees. The CuO-CeO2 catalyst prepared using co
precipitation method showed the highest activity. In addition, the highest
activity is shown on Cu0.35 (the index denotes the molar ratio Cu/(Cu + Ce))
sample and then it decreases on Cu0.5 and Cu0.6 samples.
PMID- 27483794
TI - Direct Dehydrogenation of n-Butane Over Pt/Sn/Zn-K/Al2O3 Catalyst: Effect of
Hydrogen in the Feed.
AB - Al2O3 was prepared by a sol-gel method for use as a support. Pt/Sn/Zn-K/Al2O3
catalyst was then prepared by a sequential impregnation method, and it was
applied to the direct dehydrogenation of n-butane to n-butenes and 1,3-butadiene.
Physicochemical properties of Pt/Sn/Zn-K/Al2O3 catalyst were examined by X-ray
diffraction (XRD), nitrogen adsorption-desorption isotherm, inductively coupled
plasma atomic emission spectroscopy (ICP-AES), temperature-programmed reduction
(TPR), CO chemisorption, and temperature-programmed oxidation (TPO) measurements.
In order to improve the catalyst stability, the effect of hydrogen in the feed on
the catalytic performance in the direct dehydrogenation of n-butane was studied.
The catalyst stability and reusability in the direct dehydrogenation of n-butane
was also investigated. Experimental results revealed that the addition of
hydrogen in the feed decreased conversion of n-butane and yield for total
dehydrogenation products but improved the stability of the catalyst. The
catalytic activity and stability of regenerated Pt/Sn/Zn-K/Al2O3 catalyst in the
presence of hydrogen slightly decreased compared to those of fresh Pt/Sn/Zn
K/Al2O3 catalyst due to the slight sintering of platinum particles.
PMID- 27483795
TI - Bio-Diesel Production from Deoxygenation Reaction Over Ce0.6Zr0.4O2 Supported
Transition Metal (Ni, Cu, Co, and Mo) Catalysts.
AB - Ce0.6Zr0.4O2 supported transition metal (Me = Ni, Cu, Co, and Mo) catalysts have
been investigated to screen for the catalytic activity and selectivity for
deoxygenation reaction of oleic acid. Me-Ce0.6Zr0.4O2 catalysts were prepared by
a co-precipitation method. Ni-Ce0.6Zr0.4O2 catalyst exhibited much higher oleic
acid conversion, selectivity for C9 to C17 compounds, and oxygen removal
efficiency than the others. This is mainly ascribed to the presence of free Ni
species, synergy effects between Ni and Ce0.6Zr0.4O2, and the highest BET surface
area.
PMID- 27483796
TI - Technical Advances in Intracellular Detection Using Immuno-Gold Particles: Simple
Cryofixation with Metal Contact Quick Freezing.
AB - The preparation of biological specimens using cryofixation techniques ensures
excellent visibility of intracellular structures and preserves the antigenic
sites of subcellular molecules. Hence, cryofixation is an effective method of
preparing samples for analyses using antibodies conjugated to gold nanoparticles
that are designed to detect the localization of specific target molecules within
cells. However, cryofixation cannot be utilized easily because it requires
expensive equipment and skilled technologists, resulting in a high level of
expense for researchers. Here, we describe a simple technical approach to
cryofixation that uses metal contact quick freezing followed by a modified freeze
substitution technique and immuno-gold labeling electron microscopy. Micrograph
images of cells prepared using this modified cryofixation method demonstrated its
superiority over chemical fixation for high contrast visualization of the
morphologies of cellular components and preservation of antigenicity for immuno
gold labeling. This report provides valuable technical information related to the
advancement of metal contact quick freezing techniques, which can be used to
visualize biomedical events of interest in an easy, simple, and rapid manner.
PMID- 27483797
TI - Preparation of Nano-Porous Activated Carbon Aerogel Using a Single-Step
Activation Method for Use as High-Power EDLC Electrode in Organic Electrolyte.
AB - Carbon aerogel was chemically activated with KOH using two different activation
methods (conventional activation method and single-step activation method) to
yield the nano-porous activated carbon aerogel. Both nano-porous activated carbon
aerogels exhibited a better capacitive behavior than carbon aerogel in organic
electrolyte. However, a drastic decrease in the specific capacitance with
increasing current density was observed in the ACA_C (activated carbon aerogel
prepared by a conventional activation method), which is a general tendency of
carbon electrode for EDLC in organic electrolyte. Interestingly, the specific
capacitance of ACA_S electrode (activated carbon aerogel prepared by a single
step activation method) decreased slowly with increasing current density and its
CV curve maintained a rectangular shape well even at a high scan rate of 500
mV/s. The enhanced electrochemical performance of ACA_S at a high current density
was attributed to its low ionic resistance caused by the well-developed pore
structure with appropriate pore size for easy moving of organic electrolyte ion.
Therefore, it can be concluded that single-step activation method could be one of
the efficient methods for preparation of nano-porous activated carbon aerogel
electrode for high-power EDLC in organic electrolyte.
PMID- 27483798
TI - Hydrogen Production by Steam Reforming of Liquefied Natural Gas (LNG) Over Nickel
Phosphorus-Alumina Xerogel Catalyst Prepared by a Carbon-Templating Epoxide
Driven Sol-Gel Method.
AB - A nickel-phosphorus-alumina xerogel catalyst was prepared by a carbon-templating
epoxide-driven sol-gel method (denoted as CNPA catalyst), and it was applied to
the hydrogen production by steam reforming of liquefied natural gas (LNG). For
comparison, a nickel-phosphorus-alumina xerogel catalyst was also prepared by a
similar method in the absence of carbon template (denoted as NPA catalyst). The
effect of carbon template addition on the physicochemical properties and
catalytic activities of the catalysts in the steam reforming of LNG was
investigated. Both CNPA and NPA catalysts showed excellent textural properties
with well-developed mesoporous structure. However, CNPA catalyst retained a more
reducible nickel aluminate phase than NPA catalyst. XRD analysis of the reduced
CNPA and NPA catalysts revealed that nickel sintering on the CNPA catalyst was
suppressed compared to that on the NPA catalyst. From H2-TPD and CH4-TPD
measurements of the reduced CNPA and NPA catalysts, it was also revealed that
CNPA catalyst with large amount of hydrogen uptake and strong hydrogen-binding
sites showed larger amount of methane adsorption than NPA catalyst. In the
hydrogen production by steam reforming of LNG, CNPA catalyst with large methane
adsorption capacity showed a better catalytic activity than NPA catalyst.
PMID- 27483799
TI - Catalytic Performance of Microwave Functionalized NH2-MIL-53 for Cyclic Carbonate
Synthesis from CO2 and Epoxides.
AB - The efficacy of microwave irradiation in the quaternization of amino
functionalized MIL-53 metal-organic framework (MOF) as well as the catalytic
activity of the resultant MOF in the cycloaddition of carbon dioxide with
epoxides under solvent-free conditions has been studied. A series of NH2-MIL-53
were synthesized and quaternized by reacting alkyl halide of various alkyl chains
and anions under microwave irradiation. The post-functionalized F-MIL-53-AXs were
characterized through solid-state XRD, FT-IR, XPS, and TGA. F-MIL-53-Mel prepared
by microwave method showed higher AGC yield than that by the conventional heating
method. F-MIL-53-AXs with iodide anion exhibited the best catalytic activity
irrespective of the alkyl chain length, in agreement with the generally accepting
order of nucleophilicity, Cl
1 wt% Pd/SiO2 > 1 wt% Pd/gamma-Al2O3. A
strong interaction between the palladium and support was found, which affected
the palladium surface concentration and particle size. The higher catalytic
activity of the Pd/TiO2 catalyst was attributed to the higher palladium surface
concentration and larger particle size.
PMID- 27483804
TI - Effect of Molar Concentration of NH4OH on Photocatalytic Activity in Preparation
of Nanosized TiO2 Powder from Spent Titanium Chip by Sol-Gel Method.
AB - The TiO2 powder was prepared from the spent titanium chips by applying the sol
gel method. The spent titanium chip was dissolved in HCl solution, and then NH4OH
solution was added. The molar concentration of NH4OH solution was 2 M, 4 M, 8 M,
and 10 M. Obtained TiO2 powders were calcined at 200 degrees C, 400 degrees C,
and 600 degrees C. The prepared TiO2 powder was characterized using a particle
size analysis, BET surface area, and XRD analysis. The crystal structure of the
TiO2 powder was rutile type and anatase. The highest BET surface area of TiO2
powder was 432.8 m2/g. The photocatalytic property of the TiO2 powder was
evaluated as decomposition rate of methylene blue(MB) by using a liquid phase
stirred reactor. UV source was a UV-A, and concentration of MB in most
experiments was 8 ppm. The concentration of MB was measured by absorbance at 664
nm using UV spectroscopy. Photocatalytic efficiency of prepared TiO2 powder
depended highly on concentration of NH4OH solution. The TiO2 powder prepared with
8 M-NH4OH solution showed the highest efficiency, the decomposition efficiency at
decomposition time of 2 hr and MB concentration of pH 8 was 98%.
PMID- 27483805
TI - Catalytic Decomposition of N2O at Low Temperature by Reduced Cobalt Oxides.
AB - Various forms of cobalt oxide (Co3O4 and C0203) were subsequently prepared and
tested for decomposition of N2O at low temperature in a fix bed differential
reactor at steady state conditions. These different types of oxides were prepared
by precipitation method (PM) and by calcination of commercially available CoCO3.
Commercially available cobalt oxides C03O4 and C02O3 were also tested for N2O
decomposition at different temperatures. All types of prepared and commercially
available cobalt oxide were found inactive for N2O decomposition in the presence
of oxygen at temperature less than 300 degrees C. Similar unsatisfactory results
were found at low temperature N2O decomposition after impregnation of alkali
metal (10% Na) and alkaline earth metal (10% Ba) over Co3O4. These catalysts were
then reduced under reduction media (H2 gas). It was found that after reduction
cobalt oxide catalysts became active for N2O decomposition for short time in the
presence of oxygen at low temperature. The reduced form of Co3O4 catalyst showed
enormous efficiency i.e., 98% at temperature (300 degrees C) under the same
conditions. From results it seems that Co3O4 itself is not active for N2O
decomposition but its reduced form is highly active for this reaction due to
oxidation state change of C03O4 during reduction process.
PMID- 27483806
TI - Progress on Synthesis and Applications of Cr2O3 Nanoparticles.
AB - As is known to us that nanosized chromic oxide (Cr2O3) is an important transition
metal oxide. Because it has many excellent properties, it can be used in many
fields such as pigment, catalyst, Lithium material etc. This article briefly
reviewed the preparation and applications of Cr2O3 nanoparticles. In this paper,
some specific applications will be listed according to different fields.
Nanosized chromic oxide (Cr2O3) can be obtained via many methods. A summary of
the methods have been made. The preparation methods are divided into three main
types, including vapor phase method, solid phase method and liquid phase method.
Simultaneously, different types of methods have been simply evaluated in this
paper. And the advantage and disadvantage are simply noted.
PMID- 27483807
TI - Effect of Nitrogen and Hydrogen Gases on the Synthesis of Carbon Nanomaterials
from Coal Waste Fly Ash as a Catalyst.
AB - Various reducing and inert gases have been used in the catalytic chemical vapour
deposition (CCVD) synthesis of carbon nanomaterials (CNMs). In this paper we
report on the effects that hydrogen and nitrogen gases have on the production of
CNMs from acetylene on fly ash catalysts. Parameters such as temperature and gas
environments were investigated. Transmission electron microscopy (TEM) revealed
that CNMs of various morphologies such as carbon nanofibers (CNFs) and carbon
nanospheres (CNSs) were formed. When hydrogen was used the carbonaceous products
were formed in higher yields as compared to when nitrogen was used. This could be
due to the multifunctional roles that hydrogen plays as compared to nitrogen.
Laser Raman and Mossbauer spectroscopy measurements revealed that three types of
products were formed, namely: amorphous carbon, graphitic carbon and iron
carbide. Significantly cementite (Fe3C) was identified as the main intermediate
carbide species in the catalytic growth of well-ordered CNMs.
PMID- 27483808
TI - Analysis of the Impact of Variations on Signal Electro-Migration and Optimization
of Interconnects in FinFET Designs.
AB - The An AC current induced electro-migration (EM) on clock and logic signals
becomes a significant problem even in the presence of reverse-recovery effect.
Compared to power network, clock and logic signal interconnects are much narrower
and suffer from fast switching and large driving current from FinFETs. Thus, the
high current density on those signal interconnects can cause a serious failure.
In this paper, we analyze EM on signal interconnects in 16 nm FinFET design, and
characterize the impact of process variations, e.g., lithography and etch
process, CMP (chemical-mechanical polishing) process, redundant via, etc. We also
analyze signal-line EM with transistor-level PVT (process-voltage-temperature)
variation corners. Then we optimize the signal lines with various design
approaches to mitigate EM problem in 16 nm design.
PMID- 27483809
TI - Facet-Controlled CeO2 Nanocrystals for Oxidative Coupling of Methane.
AB - Whether the catalysts of the high temperature reaction such methane oxidation
coupling has a structure-sensitive catalytic behavior or not, it is discussed and
confirmed the shape-specific impact on methane activity by designing the
catalysts with different crystal facets exposed. CeO2 nanowires enclosed by {110}
and {100} planes show the higher CH4 conversion and higher C2 hydrocarbons (C2H4
and C2H6) selectivity, compared with particle CeO2 rounded by {111} and {100}
planes, suggesting that CeO2 (110) surface favors the activation of CH4.
Encouraged by the result, to control facet-controlled synthesis of catalysts for
tailoring the catalytic properties at high temperature, the CeO2 (110) surface is
chosen as doped sites to form the doped catalyst such as Ca doped CeO2 nanowires
for OCM reaction, enhancing C2 hydrocarbons selectivity dramatically and
suppressing the deep oxidation product (CO and CO2) selectivity.
PMID- 27483810
TI - Dual Effort to Correlate the Electron Field Emission Performance of Carbon
Nanotubes with Synthesis As Well As Annealing Temperature: Theoretical Support of
the Experimental Finding.
AB - Here a dual approach has been adopted to study the effect of both synthesis as
well as annealing temperature on the electron field emission property of
differently synthesized carbon nanotubes (CNTs) that include solid state chemical
reaction as well as chemical vapour deposition (CVD). Experimental findings were
supported by theoretical simulation. All the samples were characterized by X-ray
diffraction (XRD), Fourier transformed infrared spectroscopy, Raman spectroscopy,
field emission scanning electron microscopy (FESEM) and transmission electron
microscopy (TEM). XRD as well as TEM study confirms the amorphous nature (aCNTs)
of the samples for both the synthesis techniques which is attributed to lower
synthesis temperature. Prominent morphological differences of these two types of
aCNTs are clearly observed from both FESEM and TEM images. It is found that
electron field emission characteristics of aCNTs synthesized by CVD shows better
field emission properties as compared to aCNTs synthesized by solid state
reaction. Finite element based simulation shows that temperature has prominent
effect on morphology, screening effect or degree of graphitization that leads to
improved field emission characteristics for the CVD synthesized aCNTs.
PMID- 27483811
TI - Neuromorphic System Based on CMOS Inverters and Si-Based Synaptic Device.
AB - We developed an analog neuron circuit that can work with Si-based synaptic
devices. N-channel and p-channel synaptic devices connected to current mirrors
constitute the synaptic connection and integration parts to implement the
excitation and inhibition mechanisms of biological neurons. The normal inverter
controlling delay time and the modified inverter making negative pulse constitute
the action-potential generation part to generate output action-potential.
Connecting output potential to the synaptic device, we implement the spike-timing
dependent-plasticity (STDP) mechanism, adjusting the conductance of synapse. As
we have constituted the analog neuron circuit using 4-terminal synaptic device
without additional switch and logic operation, we can emulate the operation of
the neuron with minimum number of devices and power dissipation.
PMID- 27483812
TI - The Influence of Variability Sources on SRAM Stability in 90 A Non-Rectangular
Bulk FinFET SRAM Cell.
AB - The temperature dependency of influence of variability sources on SRAM stability
were simulated and analyzed in 90 A non-rectangular Bulk FinFET SRAM cell. RDF is
the most dominant variability source. In addition, it is also shown that standard
deviation of read static noise margin (sigma(RSNM)) by WFV and RDF decreases with
increasing temperature, whereas sigma-(RSNM) by LER increases with increasing
temperature. Finally, the analyses on the simulation results mentioned above were
performed.
PMID- 27483813
TI - Applying Electrospun Gelatin/Poly(lactic acid-co-glycolic acid) Bilayered
Nanofibers to Fabrication of Meniscal Tissue Engineering Scaffold.
AB - The menisci are fibrocartilaginous tissues composed primarily of an interlacing
network of collagen fibers with nanoscale diameter. Electrospinning is a suitable
process of producing nanoscale fibers that mimic collagen fibers. In this study,
a bilayered scaffold (group B), which consists of a gelatin nanofiber mesh and a
PLGA nanofiber mesh, has been fabricated through an electrospinning method. At
the same time, we electrospun pure PLGA fibrous mesh (group A) and gelatin/PLGA
composite fibrous mesh (group C) as control groups. In order to compare all
scaffold morphologies, the scaffolds were imaged by SEM and some parameters were
measured and analyzed as following: Diameters of fibrils are from the smallest of
less than average 0.14 MUm for group C to the biggest of nearly average 0.38 MUm
for group B. The scaffolds pore diameters are from average 4.9 MUm for group A to
average 11.2 MUm for group B. Porosity rates show that the group B has the
highest porosity rate at about 91%. The scaffolds' properties were compared and
analyzed, including hydrophilicity property (water contact angle) and mechanical
properties (tensile strength). The results of water contact angle showed the
group B is the most hydrophil among the groups. The results of tensile strength
showed the tensile strength of group C is the weakest among the groups. All the
results showed significant differences between the groups. Finally, in vitro, the
meniscal cells derived from New Zealand white rabbits menisci were seeded in the
scaffolds. We observed the cells proliferation behavior in the scaffolds. All
above demonstrates that a bi-layered gelatin/PLGA scaffold reveals not only
concurrent effects of mechanics and cytocompatibility in a fibrous context, but
also a promising scaffold for future meniscal repair strategies.
PMID- 27483814
TI - Efficient Fenton Oxidation of Congo Red Dye by Magnetic MgFe2O4 Nanorods.
AB - We reported a highly active magnetic MgFe2O4 nanorods catalyst by annealing
Mg(OH)2 deposited alpha-FeOOH nanorods. The catalyst was fully characterized by X
ray diffraction (XRD), High Resolution Transmission Electron Microscopy (HRTEM),
and Vibrating Sample Magnetometer (VSM), and the results showed that the magnetic
MgFe2O4 nanorods were a diameter of 50 nm. The as-prepared MgFe2O4 nanorods were
used to catalyze Fenton oxidation of Congo red (CR) solution, and the degradation
rate of CR reached 95% after 2 h. The catalytic activity remained high after five
cycles. The magnetic MgFe2O4 nanorods could be easily separated from organic
solvent. The effects of parameters such as temperature, dosage of catalyst, and
H2O2 were also analyzed. This opens new perspectives for the synthesis of one
dimensional magnetic catalyst based on a template method and effective treatment
of aqueous hazardous dye.
PMID- 27483815
TI - Magnetic Nanoparticles: Synthesis, Characterization and Magnetic Properties of
Cobalt Aluminum Ferrite.
AB - Nanoparticles of the ferrite system CoFe(2-x)Al(x)O4 (x = 0.0, 0.3, 0.7 and 1.0)
were synthesized through the co-precipitation technique. Thermal decomposition
process and formation of a single crystalline phase were followed using thermal
differential analysis technique (DTA). X-ray powder diffraction patterns of the
samples confirmed the formation of a nano-size single spinel phase. The average
crystallite size was found to be in the range 20-63 nm for all samples. This was
further confirmed by TEM of one of the samples, with concentration x = 1.0 which
was found statistically to be 27 nm. This agrees well with the value of 24 nm
deduced by means of X-ray diffraction method for the same sample. A considerable
decrease in the intensity of the octahedral bands is observed as the aluminum
concentration increases, and even vanishes completely at x = 1.0 indicating the
migration of cations between the octahedral and tetrahedral sites. The magnetic
hysteresis loops at room temperature showed decrease in both, coercivity and
saturation magnetization as the non-magnetic Al3+ ions content increases. The
relative values of M(r0/M(s) were found to be between 0.44 and 0.31 for the
samples with a remarkable change in the squareness of the loops. This is highly
beneficial for the microwave and memory devices applications of these nano sized
ferrite system.
PMID- 27483816
TI - Analysis of the Electrical Properties of an Electron Injection Layer in Alq3
Based Organic Light Emitting Diodes.
AB - We investigated the carrier transfer and luminescence characteristics of organic
light emitting diodes (OLEDs) with structure ITO/HAT-CN/NPB/Alq3/Al, ITO/HAT
CN/NPB/Alq3/Liq/Al, and ITO/HAT-CN/NPB/Alq3/LiF/A. The performance of the OLED
device is improved by inserting an electron injection layer (EIL), which induces
lowering of the electron injection barrier. We also investigated the electrical
transport behaviors of p-Si/Alq3/Al, p-Si/Alq3/Liq/Al, and p-Si/Alq3/LiF/Al
Schottky diodes, by using current-voltage (L-V) and capacitance-voltage (C-V)
characterization methods. The parameters of diode quality factor n and barrier
height phi(b) were dependent on the interlayer materials between Alq3 and Al. The
barrier heights phi(b) were 0.59, 0.49, and 0.45 eV, respectively, and the diode
quality factors n were 1.34, 1.31, and 1.30, respectively, obtained from the I-V
characteristics. The built in potentials V(bi) were 0.41, 0.42, and 0.42 eV,
respectively, obtained from the C-V characteristics. In this experiment, Liq and
LiF thin film layers improved the carrier transport behaviors by increasing
electron injection from Al to Alq3, and the LiF schottky diode showed better I-V
performance than the Liq schottky diode. We confirmed that a Liq or LiF thin film
inter-layer governs electron and hole transport at the Al/Alq3 interface, and has
an important role in determining the electrical properties of OLED devices.
PMID- 27483817
TI - Accurate Analysis and Characterization of Silicon Field Effect Transistor-Based
Terahertz Wave Detector with Quasi-Plasma Two-Dimensional Electron Gas.
AB - We report the nonresonant plasmonic terahertz (THz) wave detector based on the
silicon (Si) field effect transistor (FET) with a technology computer-aided
design (TCAD) platform. The plasma wave behavior has been modeled by a quasi
plasma electron box as a two-dimensional electron gas (2DEG) in the channel of
the FET. The incoming alternating current (AC) signal as the THz wave radiation
can induce the direct-current (DC) voltage difference between the source and
drain, which is called the photoresponse. For accurate analysis of the modulation
and propagation of the channel electron density as the plasma wave, we have
characterized the quasi-plasma 2DEG model with two key parameters, such as quasi
plasma 2DEG length (I(QP)) and density (N(QP)). By using our normalization
method, I(QP) and N(QP) is defined exactly as extracting the average point of the
electron density. We also investigate the performance enhancement of the
plasmonic terahertz wave detector based on Si FET by scaling down the gate oxide
thickness (t(ox)), which is a significant parameter of FET-based plasmonic
terahertz detector for the channel electron density modulation. According to
scaling down t(ox), the responsivity (R(v)) and noise equivalent power (NEP),
which are the important performance metrics of the THz wave detector, have been
enhanced. The proposed methodologies will provide the advanced physical analysis
and structural design platform for developing the plasmonic terahertz detectors
operating in nonresonant regime.
PMID- 27483818
TI - Multiple Negative Differential Resistance Device by Using the Ambipolar Behavior
of Tunneling Field Effect Transistor with Fast Switching Characteristics.
AB - We propose a novel double-peak negative differential resistance (NDR)
characteristic at the conventional single-peak MOS-NDR circuit by employing
ambipolar behavior of TFET. The fluctuated voltage transfer curve (VTC) from
ambipolar inverter is analyzed with simple model and successfully demonstrated
with TFET, as a practical example, on the device simulation. We also verified
that the fluctuated VTC generates additional peak and valleys on NDR
characteristics by using circuit simulations. Moreover, by adjusting the
threshold voltage of conventional MOSFET, ultra-high 1st and 2nd peak-to-valley
current ratio (PVCR) over 10(7) is obtained with fully suppressed valley
currents. The proposed double-peak NDR circuit expected to apply on faster
switching and low power multi-functional applications.
PMID- 27483819
TI - Effects of High-Pressure Hydrogen Annealing (HPHA) on Reliability Characteristics
of RRAM.
AB - Reliability characteristics (retention and endurance) of RRAM are critical for
its practical realization and need to be improved. In this work, we confirmed the
trade-off between retention and endurance by using various top electrode
thickness conditions. The trade-off between retention and endurance
characteristics was mainly due to the different amount of oxygen in scavenging
layer (Ta) and the amount of oxygen vacancy in switching layer (HfO2). The amount
of the oxygen in scavenging layer (Ta) and the amount of the oxygen vacancy in
switching layer (HfO2) will be increased with the increase of Ta thickness.
Therefore, the thicker Ta cells have worse retention because the large amount of
oxygen in scavenging layer (Ta) can diffuse back into switching layer (HfO2) and
recombine with oxygen vacancies in the filament. However, it has longer endurance
because the large amount of oxygen vacancy in switching layer (HfO2) can be a
source of the filament. Hence, there exists a trade-off relation between
retention and endurance under the various Ta thickness conditions. To improve
both retention and endurance characteristics, we proposed a new method by using
high-pressure hydrogen annealing (HPHA). The thin Ta cells have longer retention
and worse endurance because it has small amount of both oxygen in scavenging
layer (Ta) and oxygen vacancy in switching layer (HfO2). Therefore, to generate
more oxygen vacancies in switching layer (HfO2) maintaining small amount of
oxygen in scavenging layer (Ta), we treated the samples by HPHA before Ta
deposition. Finally, we obtained both improved retention and endurance
characteristics in HfO2 based RRAM devices after high-pressure hydrogen annealing
treatment.
PMID- 27483820
TI - Synthesis of Leucas Aspera Extract Loaded Gold-PLA-PEG-PLA Amphiphilic Copolymer
Nanoconjugates: In Vitro Cytotoxicity and Anti-Inflammatory Activity Studies.
AB - Gold nanoparticles (GNPs) are synthesized using the medicinal plant Leucas Aspera
extract (LAE) and poly lactic acid-co-poly ethylene glycol-co-poly lactic acid
(PLA-PEG-PLA) copolymer by water-in-oil (W/O) emulsion method. The proposed
method of W/O emulsion technique involves synthesis of GNPs and loading of Leucas
Aspera extract on to the PLA-PEG-PLA copolymer matrix simultaneously. The
synthesized GNPs are characterized by Fourier transform infra-red (FTIR)
spectroscopy, dynamic light scattering (DLS), X-ray diffractometry (XRD) and
transmission electron microscopy (TEM). The GNPs-LAE loaded polymer NPs are
examined for the in vitro cytotoxicity on South African green monkey's kidney
cells. The GNPs-LAE loaded polymer nanoconjugates exhibit maximum up to 95% of
cell viability with 100 MUg concentration of GNPs in the sample. The GNPs-LAE
loaded polymer NPs exhibit better anti-inflammatory activity when compared to the
pure LAE.
PMID- 27483821
TI - Electrostatic Layer-By-Layer Self-Assembled Graphene/Multi-Walled Carbon
Nanotubes Hybrid Multilayers as Efficient 'All Carbon' Supercapacitors.
AB - In this work, covalently bonded graphene/carbon nanotube (Gr/CNT) conjoined
materials are fabricated as engineered three-dimensional hybrid multilayer
supercapacitors for high-performance integrated electrochemical energy storage.
Stable aqueous dispersion of polymer-modified graphene sheets are prepared in the
presence of cationic poly(ethyleneimine), PEI (PEI-Gr) for sequential or
electrostatic layer-by-layer (E-LBL) self-assembly with negatively charged acid
oxidized or functionalized multi-walled CNT (fMWCNT), forming (PEI-Gr/fMWCNT)n
architecture as "all carbon" super-capacitor, where n = 1, 2, 4, 6, 9, 12 and 15.
These films possess an interconnected network of mesoporous nanocarbon structure
with well-defined interfaces allowing sufficient surface adsorption and faster
ion transport due to short diffusion distances. They exhibit nearly rectangular
cyclic voltammograms at an exceedingly high scan rate of 1 V/s with an average
specific capacitance of -450 F g(-1) and specific energy density of 75.5 Wh kg(
1) based on electrode weight, measured at a current density of 0.3 A g(-1),
comparable to that of Ni metal hydride battery and charged/discharged within a
few seconds or a minute. This is attributed to the maximized synergistic effect
of the highest specific surface areas by preventing re-aggregation of PEI-Gr or
PEI-rGO via fMWCNT as spacers. We also determined relative contributions of the
interfacial capacitance (C(dl)) and charge transfer (R(ct)) properties of the
hybrids and investigated interfacial properties by SECM technique.
PMID- 27483822
TI - Effects of Low Temperature Anneal on the Interface Properties of Thermal Silicon
Oxide for Silicon Surface Passivation.
AB - High quality surface passivation has gained a significant importance in
photovoltaic industry for reducing the surface recombination and hence
fabricating low cost and high efficiency solar cells using thinner wafers. The
formation of good-quality SiO2 films and SiO2/Si interfaces at low processing
temperatures is a prerequisite for improving the conversion efficiency of
industrial solar cells with better passivation. High-temperature annealing in
inert ambient is promising to improve the SiO2/Si interface. However, annealing
treatments could cause negative effects on SiO2/Si interfaces due to its chemical
at high temperatures. Low temperature post oxidation annealing has been carried
out to investigate the structural and interface properties of Si-SiO2 system.
Quasi Steady State Photo Conductance measurements shows a promising effective
carrier lifetime of 420 MUs, surface recombination velocity of 22 cm/s and a low
interface trap density (D(it)) of 4 x 10(11) states/cm2/eV after annealing. The
fixed oxide charge density was reduced to 1 x 10(11)/cm2 due to the annealing at
500 degrees C. The FWHM and the Si-O peak wavenumber corresponding to the samples
annealed at 500 degrees C reveals that the Si dangling bonds in the SiO2 films
due to the oxygen defects was reduced by the low temperature post oxidation
annealing.
PMID- 27483823
TI - Fabrication and Characteristics of High Mobility InSnZnO Thin Film Transistors.
AB - In this paper, we describe the fabrication of thin film transistors (TFTs) with
amorphous indium-tin-zinc-oxide (ITZO) as the active material. A transparent ITZO
channel layer was formed under an optimized oxygen partial pressure (OPP (%) =
O2/(Ar + O2)) and subsequent annealing process. The electrical properties
exhibited by this device include field-effect mobility (MU(eff)), sub-threshold
swing (SS), and on/off current ratio (I(ON/OFF)) values of 28.97 cm2/V x s, 0.2
V/decade, and 2.64 x 10(7), respectively. The average transmittance values for
each OPP condition in the visible range were greater than 80%. The positive gate
bias stress resulted in a positive threshold voltage (V(th)) shift in the
transfer curves and degraded the parameters MU(eff) and SS. These phenomena
originated from electron trapping from the ITZO channel layer into the oxide/ITZO
interface trap sites.
PMID- 27483824
TI - Synthesis and Application of Si/Carbon Nanofiber Composites Based on Ni and Mo
Catalysts for Anode Material of Lithium Secondary Batteries.
AB - In this paper, carbon nanofibers (CNFs) and Si/carbon nanofiber composites were
synthesized for use as the anode material of lithium secondary batteries.
Catalysts were prepared based on Ni and Mo metals and CNFs were grown through
chemical vapor deposition (CVD). In addition, the grown CNFs were mixed with
silicon particles to synthesize Si/carbon nanofibers composites. The
physiochemical characteristics of the synthesized CNFs and Si/carbon nanofiber
composites were analyzed by SEM, EDS, XRD, Raman, BET and XPS. The
electrochemical characteristics were investigated by using cyclic voltammetry and
galvanostatic charge-discharge. Using CNFs and Si/carbon nanofiber composites as
the anode material, three electrode cells were assembled and the electrochemical
characteristics were measured using LiPF6 and LiClO4 as electrolytes. As a result
of the galvanostatic charge-discharge of CNFs that were grown through catalysts
with Ni and Mo concentration ratio of 6:4, the initial discharge capacity when
using LiPF6 as the electrolyte was 570 mAh/g and the retention rate was 15.05%.
In the case of using LiClO4 as the electrolyte, the initial discharge capacity
was 263 mAh/g and the retention rate was 67.23%.
PMID- 27483825
TI - Analysis of Current Fluctuation Due to Trap and Percolation Path in Nano-Scale
Bulk FinFET.
AB - An electron in the channel can be trapped into the trap inside gate oxide and
detrapped into the channel, resulting in the fluctuation in drain current. To
investigate the drain current fluctuation (DeltaI(D)) caused by
trapping/detrapping of an electron in 22 nm bulk FinFET, 3-D device simulation
was performed extensively. The DeltaI(D) is changed by changing the position of
the trap in the gate oxide along the surface of fin body. In the bulk FinFET, the
trap located near the center of side surface of the fin body gives the larger
DeltaI(D) compared to those of the traps located at the top center, top corner,
and side bottom. At a fixed trap position, the shallower trap depth (x(T)) from
the interface between the gate oxide and the fin body gives the lager DeltaI(D).
With decreasing fin width (W(fin)) and fin height (H(fin)), the DeltaI(D)
increases. Especially, decreasing H(fin) increases DeltaI(D) significantly. As
the trap is close to a percolation path, the DeltaI(D) also increases.
PMID- 27483826
TI - Post-Cleaning Effect on a HfO2 Gate Stack Using a NF3/NH3 Plasma.
AB - The effects of dry cleaning of a HfO2 gate stack using NF3 only and a NF3/NH3 gas
mixture plasma were investigated. The plasma dry cleaning process was carried out
after HfO2 deposition using an indirect down-flow capacitively coupled plasma
(CCP) system. An analysis of the chemical composition of the HfO2 gate stacks by
XPS indicated that fluorine was incorporated into the HfO2 films during the
plasma dry cleaning. Significant changes in the HfO2 chemical composition were
observed as a result of the NF3 dry cleaning, while they were not observed in
this case of NF3/NH3 dry cleaning. TEM results showed that the interfacial layer
(IL) between the HfO2 and Si thickness was increased by the plasma dry cleaning.
However, in the case of NF3/NH3 dry cleaning using 150 W, the IL thickness was
suppressed significantly compared to the sample that had not been dry cleaned.
Its electrical properties were also improved, including the low gate leakage
currents, and reduced EOT. Finally, the finding show that the IL thickness of the
HfO2 gate stack can be controlled by using the novel NF3/NH3 dry cleaning process
technique without any the significant changes in chemical composition and metal
oxide-semiconductor (MOS) capacitor characteristics.
PMID- 27483827
TI - Synthesis of Fe Doped ZnO Nanowire Arrays that Detect Formaldehyde Gas.
AB - Owing to their chemical and thermal stability and doping effects on providing
electrons to the conduction band, doped ZnO nanowires have generated interest for
use in electronic devices. Here we report hydrothermally grown Fe-doped ZnO
nanowires and their gas-sensing properties. The synthesized nanowires have a high
crystallinity and are 60 nm in diameter and 1.7 MUm in length. Field-emission
scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X
ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) are employed to
understand the doping effects on the microstructures and gas sensing properties.
When the Fe-doped ZnO nanowire arrays were evaluated for gas sensing, responses
were recorded through changes in temperature and gas concentration. Gas sensors
consisting of ZnO nanowires doped with 3-5 at.% Fe showed optimum formaldehyde
(HCHO) sensing performance at each working temperature.
PMID- 27483828
TI - Resistive Switching in Al/Al2O3/TiO2/Al/PES Flexible Device for Nonvolatile
Memory Application.
AB - Resistive switching memory devices with superior properties are possibly used in
next-generation nonvolatile memory to replace the flash memory. In addition,
flexible electronics has also attracted much attention because of its light
weight and flexibility. Therefore, an Al/Al2O3/TiO2/Al/PES flexible resistive
switching memory is employed in this study. The resistive switching
characteristics and stability of the flexible device are improved by inserting
the Al2O3 film. The resistive switching of the flexible device can be repeated
over hundreds of times after the bending test. A possible resistive switching
model of the flexible device is also proposed. In addition, the non-volatility of
the flexible device is demonstrated. Based on our research results, the proposed
Al2O3/TiO2-based resistive switching memory is possibly used in next-generation
flexible electronics and nonvolatile memory applications.
PMID- 27483829
TI - Conformational, Optoelectronic and Vibrational Properties of the Entacapone
Molecule: A Quantum Chemistry Study.
AB - A quantum chemistry study were carried out looking for the conformational,
optoelectronic and vibrational properties of the entacapone molecule, an
efficient drug used in the Parkinson's disease treatment. Classical annealing was
performed to explore the entacapone's molecular configurations, searching for
optimal geometries. The quantum optimization calculations were made using three
different functional combination levels of the density functional theory (DFT).
The structural data (bond length, bond and torsion angles), charge population
analysis (absorption spectra) and molecular orbital study (HOMO and LUMO) were
obtained considering the lower energy optimized conformation of the entacapone
molecule. Furthermore, a complete assignment of the harmonic vibrational
frequencies were achieved through their infrared (IR) and Raman spectra.
PMID- 27483830
TI - Graphene Oxide Modified TiO2 Micro Whiskers and Their Photo Electrochemical
Performance.
AB - Harnessing the solar energy and producing clean fuel hydrogen through efficient
photo-electrochemical water splitting has remained one of the most challenging
endeavors in materials science. The core problem is to develop a suitable photo
catalyst material that absorbs a significant part of the solar spectrum and
produces electron-hole pairs that can be easily separated without recombination.
In the recent times, the composite of Titanium dioxide with graphene have been
investigated to explore the advantages of both class of materials. Here we report
on the photo-electrochemical properties of reduced graphene oxide functionalised
TiO2 whiskers. The TiO2 whiskers are obtained from potassium titanium oxide
(KTi8O16) synthesized through hydrothermal technique followed by ion exchange
method and heat treatment. Graphene oxide was deposited on the as prepared TiO2
whiskers using hydrothermal method. As formed samples were characterized by Raman
spectroscopy to confirm the presence of reduced graphene oxide (RGO) attached to
TiO2 whiskers. Comparative photo electrochemical studies were carried out for
TiO2 and reduced graphene oxide modified TiO2 whiskers. Among these, RGO modified
TiO2 whiskers show significantly higher photo current density possibly due to
enhancement in charge separation ability and longer electron life times.
PMID- 27483831
TI - The Role of Nanocrystal Size in Solution Processable CdSe:P3HT Hybrid
Photovoltaic Devices.
AB - Hybrid photovoltaic devices were fabricated using different sizes of CdSe quantum
dots with different loading concentrations in P3HT matrix. CdSe quantum dots were
synthesized chemically using olive oil as the capping agent, instead of toxic
phosphine. The efficiency of hybrid poly-(3-hexylthiophene-2,5-diyl) P3HT:CdSe
photovoltaic device was found to depend on the size as well as the loading of the
nanocrystals. A maximum power conversion efficiency of -0.8% was achieved under
AM1.5G solar illumination for the device with -5.3 nm CdSe nanocrystals. A hybrid
photovoltaic device was demonstrated on polyethylene terephthalate (PET)
substrates paving the way to achieve flexible,transparent and printable devices.
PMID- 27483832
TI - Boron Oxygen Pair Effect in p+ Emitter and Nanosized Boron Rich Layer by Fold
Coordination Analysis for Crystalline Silicon Solar Cell Applications.
AB - N-type substrates possess better material characteristics than p-type substrates
for high efficiency mass producible Si solar cells with HIT, IBC structures. The
major drawbacks of these structures are a complicated fabrication process and an
expensive unit cost. In this paper, the boron emitter doping profile of a
nanosized boron rich layer (BRL), for which the boron and oxygen concentrations
are correlated, is optimized to fabricate high efficiency solar cells on an n
type substrate. Boron doping was carried out using a BBr3 furnace with varying
oxygen gas ratios and the surface was treated with acid etching. The effect of
the oxygen on the nanosized BRL was analyzed using both FTIR spectroscopy and
XPS, where by conductivity and the Si-B bond were observed for the three-fold and
four-fold coordinated borons, respectively. The results showed that the oxygen
quantities in the boron doped emitter and the nanosized BRL affected the
characteristics of the solar cell. Regarding the solar cells that were fabricated
using the boron emitter and shallow emitter (90 ohm/sq) processes, the open
circuit voltage increased by 54 mV and the short circuit current (J(sc))
increased by 3.7 mA/cm2. The J(sc) increase was due to an increased quantum
efficiency in the short wavelength range. The shallow emitter etch back process
minimized the boron-oxygen defects in the doping profile.
PMID- 27483833
TI - Trap Profiling Based on Frequency Varied Charge Pumping Method for Hot Carrier
Stressed Thin Gate Oxide Metal Oxide Semiconductors Field Effect Transistors.
AB - In this study, pulse frequency and reverse bias voltage is modified in charge
pumping and advanced technique is presented to extract oxide trap profile in hot
carrier stressed thin gate oxide metal oxide semiconductor field effect
transistors (MOSFETs). Carrier trapping-detrapping in a gate oxide was analyzed
after hot carrier stress and the relationship between trapping depth and
frequency was investigated. Hot carrier induced interface traps appears in whole
channel area but induced border traps mainly appears in above pinch-off region
near drain and gradually decreases toward center of the channel. Thus, hot
carrier stress causes interface trap generation in whole channel area while most
border trap generation occurs in the drain region under the gate. Ultimately,
modified charge pumping method was performed to get trap density distribution of
hot carrier stressed MOSFET devices, and the trapping-detrapping mechanism is
also analyzed.
PMID- 27483834
TI - Effects of Sulfurization Temperature on Cu(In, Ga)S2 Thin Film Solar Cell
Performance by Rapid Thermal Process.
AB - Cu(In, Ga)S2 (CIGS) absorbers were prepared using two-step process. Cu-In-Ga
precursors were deposited by sputtering method and then were sulfurized by rapid
thermal process based on H2S gas. Sulfurization temperature was changed from 470
degrees C to 510 degrees C. As the processing temperature increased, larger
grains and denser absorbers were observed. The polycrystalline chalcopyrite
structure of CuInGaS2 was shown in all samples, and their XRD peak was dominantly
observed at (112) direction. CIGS thin film solar cells were fabricated with wide
bandgap absorbers obtained by varying sulfurization temperature. The best
efficiency was shown with the processing temperature of 490 degrees C and 8.93%
with 1.507 eV of wide optical bandgap.
PMID- 27483835
TI - Fabrication of InGaZnO Nonvolatile Memory Devices at Low Temperature of 150
degrees C for Applications in Flexible Memory Displays and Transparency Coating
on Plastic Substrates.
AB - We directly deposited amorphous InGaZnO (a-IGZO) nonvolatile memory (NVM) devices
with oxynitride-oxide-dioxide (OOO) stack structures on plastic substrate by a DC
pulsed magnetron sputtering and inductively coupled plasma chemical vapor
deposition (ICPCVD) system, using a low-temperature of 150 degrees C. The
fabricated bottom gate a-IGZO NVM devices have a wide memory window with a low
operating voltage during programming and erasing, due to an effective control of
the gate dielectrics. In addition, after ten years, the memory device retains a
memory window of over 73%, with a programming duration of only 1 ms. Moreover,
the a-IGZO films show high optical transmittance of over 85%, and good uniformity
with a root mean square (RMS) roughness of 0.26 nm. This film is a promising
candidate to achieve flexible displays and transparency on plastic substrates
because of the possibility of low-temperature deposition, and the high
transparent properties of a-IGZO films. These results demonstrate that the a-IGZO
NVM devices obtained at low-temperature have a suitable programming and erasing
efficiency for data storage under low-voltage conditions, in combination with
excellent charge retention characteristics, and thus show great potential
application in flexible memory displays.
PMID- 27483836
TI - Highly Durable Ti-Mesh Based Triboelectric Nanogenerator for Self-Powered Device
Applications.
AB - We describe a highly durable Ti-mesh based triboelectric nanogenerator (Ti-TENG)
with a sandwich structure that harvests electrical energy from contact
electrification. The electrical output from the fabricated Ti-TENG by compressing
and releasing strain was measured under different applied loads and frequencies.
The Ti-TENG generated a peak voltage and current up to -1.1 V and -14 nA at an
applied force of 30 N and frequency of 1.1 Hz. Obtained potentials were used to
charge a capacitor and power a commercially available light emitting diode (LED).
In particular, the Ti-TENG, which exhibited high electrical stability, can be
used in applications requiring high levels of robustness and durability. For
example, the Ti-TENG was applied as step counter while walking and running,
demonstrating its capability to self-power devices. We believe that the device
provides a highly promising, robust and durable platform for self-powered
applications that effectively harnesses energy from mechanical movements.
PMID- 27483837
TI - Hydrogenated Amorphous Silicon Germanium Active Layer for Top Cell of a Multi
Junction Cell Structure.
AB - Intrinsic hydrogenated amorphous silicon-germanium (a-SiGe:H) alloy is generally
used in the bottom cell because of its low band gap. The a-SiGe:H has a higher
photo conductivity in comparison to the a-Si:H; thus, it is expected that the a
SiGe:H can show better short circuit current density than that of the a-Si:H
based solar cell. Therefore, we optimized a-SiGe:H active layer that can be a
suitable choice for the front cell of a multi junction.solar cell. Furthermore,
we carried out a comparative study of the solar cells that have a-SiGe:H and a
Si:H as respective active layers. The a-SiGe:H based solar cells show higher
short circuit current density, while the a-Si:H based cells show higheropen
circuit voltage. The current-voltage characteristics of these cells are as
follows: (a) V(oc) = 770 mV, J(sc) = 15.0 mA/cm2, FF = 64.5%, and eta = 7.47% for
a-SiGe:H based cell; and (b) V(oc) = 826 mV, J(sc) = 13.63 mA/cm2, FF = 72.0%,
and eta = 8.1% for a-Si:H based cell.
PMID- 27483838
TI - Improvement of Charge Transportation in Si Quantum Dot-Sensitized Solar Cells
Using Vanadium Doped TiO2.
AB - The multiple exciton generation characteristics of quantum dots have been
expected to enhance the performance of photochemical solar cells. In previous
work, we first introduced Si quantum dot for sensitized solar cells. The Si
quantum dots were fabricated by multi-hollow discharge plasma chemical vapor
deposition, and were characterized optically and morphologically. The Si quantum
dot-sensitized solar cells had poor performance due to significant electron loss
by charge recombination. Although the large Si particle size resulted in the
exposure of a large TiO2 surface area, there was a limit to ho much the particle
size could be decreased due to the reduced absorbance of small particles.
Therefore, this work focused on decreasing the internal impedance to improve
charge transfer. TiO2 was electronically modified by doping with vanadium, which
can improve electron transfer in the TiO2 network, and which is stable in the
redox electrolyte. Photogenerated electrons can more easily arrive at the
conductive electrode due to the decreased internal impedance. The dark
photovoltaic properties confirmed the reduction of charge recombination, and the
photon-to-current conversion efficiency reflected the improved electron transfer.
Impedance analysis confirmed a decrease in internal impedance and an increased
electron lifetime. Consequently, these improvements by vanadium doping enhanced
the overall performance of Si quantum dot-sensitized solar cells.
PMID- 27483839
TI - Salicylic Acid-Based Organic Dyes Acting as the Photosensitizer for Solar Cells.
AB - A D-pi-A metal-free organic dye, featuring salicylic acid as a novel
acceptor/anchoring unit, has been designed, synthesized and applied to dye
sensitized solar cell. The detailed photophysical, electrochemical, photovoltaic
and sensitizing properties of the organic dye were investigated, in addition to
the computational studies of the dye and dye-(TiO2)6 system. A solar cell device
using this new organic dye as a sensitizer produced a solar to electric power
conversion efficiency (PCE) of 3.49% (J(sc) = 6.69 mAcm-2, V(oc) = 0.74 V and ff
= 0.70) under 100 mWcm(-2) simulated AM 1.5 G solar irradiation, demonstrating
that the salicylic acid-based organic dye is a suitable alternative to currently
used organometallic dyes.
PMID- 27483840
TI - Method for Fabricating Textured High-Haze ZnO:Al Transparent Conduction Oxide
Films on Chemically Etched Glass Substrates.
AB - We developed a technique for forming textured aluminum-doped zinc oxide (ZnO:Al)
transparent conductive oxide (TCO) films on glass substrates, which were etched
using a mixture of hydrofluoric (HF) and hydrochloric (HCl) acids. The etching
depth and surface roughness increased with an increase in the HF content and the
etching time. The HF-based residues produced insoluble hexafluorosilicate anion-
and oxide impurity-based semipermeable films, which reduced the etching rate.
Using a small amount of HCl dissolved the Ca compounds, helping to fragment the
semipermeable film. This formed random, complex structures on the glass
substrates. The angled deposition of three layers of ZnO:Al led to the synthesis
of multiscaled ZnO:Al textures on the glass substrates. The proposed approach
resulted in textured ZnO:Al TCO films that exhibited high transmittance (-80%)
and high haze (> 40%) values over wavelengths of 400-1000 nm, as well as low
sheet resistances (< 18 Omega/sq)..Si tandem solar cells based on the ZnO:Al
textured TCO films exhibited photocurrents and cell efficiencies that were 40%
higher than those of cells with conventional TCO films.
PMID- 27483841
TI - Characteristics of Nitrogen Doped Diamond-Like Carbon Films Prepared by
Unbalanced Magnetron Sputtering for Electronic Devices.
AB - Synthetic diamond-like carbon (DLC) is a carbon-based material used mainly in
cutting tool coatings and as an abrasive material. The market for DLC has
expanded into electronics, optics, and acoustics because of its distinct
electrical and optical properties. In this work, n-doped DLC (N:DLC) films were
deposited on p-type silicon substrates using an unbalanced magnetron sputtering
(UBMS) method. We investigated the effect of the working pressure on the
microstructure and electrical properties of n-doped DLC films. The structural
properties of N:DLC films were investigated by Raman spectroscopy and SEM-EDX,
and the electrical properties of films were investigated by observing the changes
in the resistivity and current-voltage (I-V) properties. The N:DLC films prepared
by UBMS in this study demonstrated good conducting and physical properties with n
doping.
PMID- 27483842
TI - Electrical Characteristics of Metal-Oxide-Semiconductor Capacitor with High
kappa/Metal Gate Using Oxygen Scavenging Process.
AB - It has been widely accepted that the mismatch of lattice constants between HfO2
and Si generates interface traps at the HfO2-Si interface, which causes the
degradation of device performances. For better interface quality, very thin SiO2
film (< 2 nm) has been inserted as an interlayer (IL) between HfO2 and Si despite
of the increase of EOT. In order to obtain both the better interface quality and
the reduction of EOT, we used Ti metal on HfO2/IL SiO2 stack as a scavenging
layer to absorb oxygens in the SiO2 and various annealing conditions were applied
to optimize the thickness of the SiO2. As a result, we can effectively shrink the
EOT from 3.55 nm to 1.15 nm while maintaining the same physical thickness of gate
stacks. Furthermore, the diffusion of oxygen was confirmed by high resolution
transmission electron microscopy (HRTEM) and time-of-flight secondary ion mass
Spectrometry (SIMS).
PMID- 27483843
TI - The Analysis of Characteristics in Dry and Wet Environments of Silicon Nanowire
Biosensor.
AB - Our study investigates differences in sensitivity of dry and wet environment in
the field of biosensing experiment in detail and depth. The sensitivity of
biosensing varies by means of surrounding conditions of silicon nanowire field
effect transistor (SiNW FET). By examining charged polymer reaction in the
silicon nanowire transistor (SiNW), we have discovered that the threshold voltage
(V(T)) shift and change of subthreshold slope (SS) in wet environment are smaller
than that of the air. Furthermore, we analyzed the sensitivity through modifying
electrolyte concentration in the wet condition, and confirmed that V(T) shift
increases in low concentration condition of phosphate buffered saline (PBS) due
to the Debye length. We believe that the results we have found in this study
would be the cornerstone in contributing to advanced biosensing experiment in the
future.
PMID- 27483844
TI - Interfacial Layer Control by Dry Cleaning Technology for Polycrystalline and
Single Crystalline Silicon Growth.
AB - Native oxide removal prior to poly-Si contact and epitaxial growth of Si is the
most critical technology to ensure process and device performances of poly-Si
plugs and selective epitaxial growth (SEG) layers for DRAM, flash memory, and
logic device. Recently, dry cleaning process for interfacial oxide removal has
attracted a world-wide attention due to its superior passivation properties to
conventional wet cleaning processes. In this study, we investigated the surface
states of Si substrate during and after dry cleaning process, and the role of
atomic elements including fluorine and hydrogen on the properties of subsequent
deposited silicon layer using SIMS, XPS, and TEM analysis. The controlling of
residual fluorine on the Si surface after dry cleaning is a key factor for clean
interface. The mechanism of native oxide re-growth caused by residual fluorine
after dry cleaning is proposed based on analytical results.
PMID- 27483845
TI - GaN Epitaxial Layer Grown with Conductive Al(x)Ga(1-x)N Buffer Layer on SiC
Substrate Using Metal Organic Chemical Vapor Deposition.
AB - This study investigated GaN epitaxial layer growth with a conductive Al(x)Ga(1
x)N buffer layer on n-type 4H-SiC by high-temperature metalorganic chemical vapor
deposition (HT-MOCVD). The Al composition of the Al(x)Ga(1-x)N buffer was varied
from 0% to 100%. In terms of the crystal quality of the GaN layer, 79% Al was the
optimal composition of the Al(x)Ga(1-x)N buffer layer in our experiment. A
vertical conductive structure was fabricated to measure the current voltage (I-V)
characteristics as a function of Al composition, and the I-V curves showed that
the resistance increased with increasing Al concentration of the Al(x)Ga(1-x)N
buffer layer.
PMID- 27483846
TI - Dual-Gate p-GaN Gate High Electron Mobility Transistors for Steep Subthreshold
Slope.
AB - A steep subthreshold slope characteristic is achieved through p-GaN gate HEMT
with dual-gate structure. Obtained subthreshold slope is less than 120 MUV/dec.
Based on the measured and simulated data obtained from single-gate device,
breakdown of parasitic floating-base bipolar transistor and floating gate charged
with holes are responsible to increase abruptly in drain current. In the dual
gate device, on-current degrades with high temperature but subthreshold slope is
not changed. To observe the switching speed of dual-gate device and transient
response of drain current are measured. According to the transient responses of
drain current, switching speed of the dual-gate device is about 10(-5) sec.
PMID- 27483847
TI - Reaction Mechanism Underlying Atomic Layer Deposition of Antimony Telluride Thin
Films.
AB - The mechanism underlying the deposition of SbTe films by alternating exposures to
Sb(NMe2)3 and Te(GeMe3)2 was investigated. Sb(NMe2)3 and Te(GeMe3)2 were selected
because they have very high vapor pressure and are free of Si, Cl, and O atoms in
the molecules. The mechanism of deposition was proposed by density functional
theory (DFT) calculation and was verified by in-situ quartz crystal microbalance
(QCM) analysis. DFT calculation expected the ligand-exchange reactions between
the Sb and Te precursors to form Me2NGeMe3 as the byproduct. QCM analysis
indicated that a single -NMe2 group in Sb(NMe2)3 reacts with -TeGeMe3 on the
surface to form an Sb2Te3 film, and that a small fraction of Sb is incorporated
into the film by the thermal decomposition of Sb(NMe2)3. The Te(GeMe3)2 molecules
were thermally stable up to 120 degrees C, while the Sb(NMe2)3 molecules
decomposed at temperatures of 60 degrees C and higher. Sb-rich SbTe films with
different Sb contents were prepared by controlling the partial decomposition of
Sb(NMe2)3 molecules, which was enhanced by increasing the pulse time of the
precursor.
PMID- 27483848
TI - Bacteria-Directed Construction of ZnO/CdS Hollow Rods and Their Enhanced
Photocatalytic Activity.
AB - Zinc oxide (ZnO) hollow rods were fabricated by precipitation method with
Bacillus subtilis as template. CdS nanoparticles were then decorated on the
surface of the ZnO rods through hydrothermal method. The as-prepared samples were
characterized using X-ray diffraction, scanning electron microscopy, high
resolution transmission electron microscope and ultraviolet-visible spectroscopy
techniques. The ZnO/CdS composite hollow rods copied the morphology of Bacillus
subtiis. A possible formation mechanism of the rods was proposed. The
photocatalytic activity of the samples was further evaluated through the
photodegradation of Rhodamine B under a simulated solar-light irradiation.
Results indicated that the photocatalytic activity of the rods improved greatly.
PMID- 27483849
TI - Preparation, Characterization and Intracellular Imaging of 2,4
Dichlorophenoxyacetic Acid Conjugated Gold Nanorods.
AB - Visualizing the biodistribution of pesticides inside living cells is great
importance for enhancing targeting of pesticides. Here we reported for the first
time that gold nanorods (Au NRs) with size of 39.4 nm x 11.3 nm could be used as
a fluorescent tracer to examine the distribution of a typical herbicide, 2,4
dichlorophenoxyacetic acid (2,4-D), in tobacco bright yellow 2 (BY-2) cells. The
nanostructures of hybrid materials were analyzed by using Raman spectra and X-ray
photoelectron spectroscopy (XPS), including spectra assignments and electronic
property. These data revealed 2,4-D has successfully conjugated MP-Au NRs
according to Raman and XPS. The biodistribution of the conjugates inside BY-2
cells was directly examined at 12 and 24 h by the two-photon microscopy. The
intensity of two-photon luminescence (TPL) inside cells demonstrated that the
conjugates could be localized and excluded by BY-2 cells. Thus, this labeling
approach opens up new avenues to the facile and efficient labeling of pesticides.
PMID- 27483850
TI - The Influence of Chelating Agent on the Structural and Magnetic Properties of
CoFe2O4, Nanoparticles.
AB - We have studied the influence of chelating agents (glycerin and sucrose) on the
structural and magnetic properties of cobalt ferrite (CoFe2O4) nanoparticles
synthesized via co-precipitation method. The Rietveld refinements from X-ray
diffraction patterns confirm that all samples are single phase identified in a
cubic crystalline system belonging to the space group Fd-3m. Besides, we have
verified that the addition of chelating agents produces a decreasing in the
particles average size from 14(2) to 5(1) nm. Magnetization measurements as a
function of temperature show a decrease in the blocking temperature (T(B)) to
sample obtained with addition of sucrose. A superparamagnetic behavior at room
temperature was observed by magnetic measurements as function of field in the
sample with 0.020 mol/L of sucrose. The results show that character chelating of
sucrose reduces the coalescence effect and magnetic interaction in the CoFe2O4
nanoparticles. These results suggest that sucrose could be an alternative to
control the structural and magnetic properties of other oxides nanoparticles.
PMID- 27483851
TI - Enhanced Cytotoxicity of Biomolecules Loaded Metallic Silver Nanoparticles
Against Human Liver (HepG2) and Prostate (PC3) Cancer Cell Lines.
AB - Green nanoparticle synthesis was achieved using environmentally acceptable plant
extracts reducing and capping agents. The present study was based on assessments
to the anticancer activities to determine the effect of synthesized silver
nanoparticles (AgNPs) from three medicinal plants on human liver (HepG2) and
prostate (PC3) cancer cell lines. The synthesis of AgNPs using Plumbago zeylanica
(Pz), Semecarpus anacardium (Sa) and Terminalia arjuna (Ta) plant extracts in the
reaction mixture was monitored by UV-visible spectroscopy. FTIR results clearly
illustrated that the plant extracts containing prominent peaks of functional
groups and biomolecules viz., tannins, phenols, flavonoids and triterpenoids
those act as capping agents and involved in the stabilization of the synthesised
silver nanoparticles. Synthesized AgNPs were spherical and cuboid in shape which
is determined by SEM. Average size of the AgNPs were between 80-98, 60-95 and 34
70 nm for PzAgNPs, SaAgNPs and TaAgNPs, respectively. Further, the synthesized
AgNPs were characterized by XRD, EDX, DLS and Zeta potential analysis. Moreover,
the synthesized AgNPs exhibited a dose-dependent cytotoxicity against human liver
and prostate cancer cell lines. The inhibitory concentration (IC50) values of
HepG2, PC3 and Vero cells were found to be 70.97, 58.61, 96.41; 10.04, 42.77,
83.86; and 28.42, 41.78, 69.48 MUg/ml for PzAgNPs, SaAgNPs and TaAgNPs at 48 h
incubation. An induction of apoptosis was confirmed by DNA fragmentation,
Hoechst, Rhodamine and AO/EtBr staining. The present results strongly suggested
that the AgNPs synthesized using P. zeylanica, S. anacardium and T. arjuna
extracts showed potential anticancer activity of HepG2 and PC3 cell lines.
PMID- 27483852
TI - Naturally Produced Co/CoO Nanocrystalline Magnetic Multilayers: Structure and
Inverted Hysteresis.
AB - Cobalt-based multilayers with excellent sequencing are grown via radiofrequency
magnetron sputtering with the use of one Co target and natural oxidation. The Co
layers are continuous, fully textured {111} and have the face centered cubic
structure. At the end of deposition of each Co layer air is let to flow into the
vacuum chamber via a fine (leak) valve. The top of Co is oxidized. The oxidized
layers consist of cubic CoO crystallites. Near the film surface hexagonal Co(OH)2
is also detected. Magneto-optical Kerr effect hysteresis loops show in-plane
magnetized films. The magnetic saturation field in the out-of-plane measurements
is large exceeding 12 kOe. This observation supports indirectly the fact that Co
is face centered cubic; if it was c-axis textured hexagonal the
magnetocrystalline anisotropy would be large resulting in smaller values of the
saturation field. As the Co-layer thickness decreases the in-plane loops show
reduced remanence, slow approach to magnetic saturation and the out-of-plane
loops show inverted hysteresis and/or crossing loop features with sizeable
remanence. The effects are discussed with respect to the enhanced orbital
magnetic moment of Co and the antiferromagnetic coupling between Co spins at the
Co/CoO interface.
PMID- 27483853
TI - Influence of Heat Treatment Conditions on the Properties of Vanadium Oxide Thin
Films for Thermochromic Applications.
AB - In present work, the effects of the heat treatment on the structural, optical,
and thermochromic properties of vanadium oxide films were investigated. Vanadium
dioxide (VO2) thin films were deposited on glass substrate by reactive pulsed DC
magnetron sputtering from a vanadium metal target in mixture atmosphere of argon
and oxygen gas. Various heat treatment conditions were applied in order to
evaluate their influence on the crystal phases formed, surface morphology, and
optical properties. The films were characterized by an X-ray diffraction (XRD) in
order to investigate the crystal structure and identify the phase change as post
annealing temperature of 500-600 degrees C for 5 minutes. Surface conditions of
the obtained VO2(M) films were analyzed by field emission scanning electron
microscopy (FE-SEM) and the semiconductor-metal transition (SMT) characteristics
of the VO2 films were evaluate by optical spectrophotometry in the UV-VIS-NIR,
controlling temperature of the films.
PMID- 27483854
TI - Characteristics of SnO2:Sb Films as Transparent Conductive Electrodes of Flexible
Inverted Organic Solar Cells.
AB - Antimony-doped tin oxide (ATO) films were deposited on polyethersulfone (PES)
substrates by means of a radio frequency (RF) magnetron sputtering method, using
a SnO2 target mixed with 6 wt% Sb at room temperature and using various RF
powers; these films were used as transparent electrodes in inverted organic solar
cells (IOSC). We investigated the structural, optical, and electrical properties
of the resulting films by means of various analyses, including X-ray diffraction
(XRD), UV-visible spectroscopy, and Hall effect measurements. The crystallinity
and conductivity of the ATO films were increased by increasing the RF power used.
Based on the experimental data acquired, we fabricated IOSCs based on ATO
electrodes deposited by using various conditions. Each IOSC device was composed
of an ATO electrode, a ZnO buffer layer, a photoactive layer (P3HT:PCBM), and an
Al cathode. The IOSC based on an ATO electrode fabricated at the RF power of 160
W exhibited good device performance due to the electrode's high conductivity and
crystallinity.
PMID- 27483855
TI - Effective Light Trapping in Thin Film Silicon Solar Cells with Nano- and
Microscale Structures on Glass Substrate.
AB - For thin film silicon-based solar cells, effective light trapping at a broad
range of wavelengths (400-1100 nm) is necessary. Normally, etching is only
carried out with TCOs, such as SnO2:F and impurity doped ZnO, to form nano-sized
craters in the surface morphology to confer a light trapping effect. However, in
this study, prior to ZnO:Al etching, periodic structures on the glass substrates
were made by photolithography and wet etching to increase the light scattering
and internal reflection. The use of periodic structures on the glass substrate
resulted in higher haze ratios in the range from 550 nm to 1100 nm, which is the
optical absorption wavelength region for thin film silicon solar cells, than
obtained by simple ZnO:Al etching. The periodically textured glass with micro
sized structures compensates for the low haze ratio at the middle and long
wavelengths of wet etched ZnO:Al. ZnO:Al was deposited on the periodically
textured glass, after which the ZnO:Al surface was also etched randomly using a
mixed acid solution to form nano-sized craters. The thin film silicon solar cells
with 350-nm-thick amorphous silicon absorber layer deposited on the periodic
structured glass and etched ZnO:Al generated up to 10.68% more photocurrent, with
11.2% increase of the conversion efficiency compared to the cell deposited on
flat glass and etched ZnO:Al.
PMID- 27483856
TI - Improving Memory Characteristics of Hydrogenated Nanocrystalline Silicon
Germanium Nonvolatile Memory Devices by Controlling Germanium Contents.
AB - Nonvolatile memory (NVM) with silicon dioxide/silicon nitride/silicon oxynitride
(ONO(n)) charge trap structure is a promising flash memory technology duo that
will fulfill process compatibility for system-on-panel displays, down-scaling
cell size and low operation voltage. In this research, charge trap flash devices
were fabricated with ONO(n) stack gate insulators and an active layer using
hydrogenated nanocrystalline silicon germanium (nc-SiGe:H) films at a low
temperature. In this study, the effect of the interface trap density on the
performance of devices, including memory window and retention, was investigated.
The electrical characteristics of NVM devices were studied controlling Ge content
from 0% to 28% in the nc-SiGe:H channel layer. The optimal Ge content in the
channel layer was found to be around 16%. For nc-SiGe:H NVM with 16% Ge content,
the memory window was 3.13 V and the retention data exceeded 77% after 10 years
under the programming condition of 15 V for 1 msec. This showed that the memory
window increased by 42% and the retention increased by 12% compared to the nc
Si:H NVM that does not contain Ge. However, when the Ge content was more than
16%, the memory window and retention property decreased. Finally, this research
showed that the Ge content has an effect on the interface trap density and this
enabled us to determine the optimal Ge content.
PMID- 27483857
TI - Characteristics of W Doped Nanocrystalline Carbon Films Prepared by Unbalanced
Magnetron Sputtering.
AB - Nanocrystalline tungsten doped carbon (WC) films were prepared by unbalanced
magnetron sputtering. Tungsten was used as the doping material in carbon thin
films with the aim of application as a contact strip in an electric railway. The
structural, physical, and electrical properties of the fabricated WC films with
various DC bias voltages were investigated. The films had a uniform and smooth
surface. Hardness and frication characteristics of the films were improved, and
the resistivity and sheet resistance decreased with increasing negative DC bias
voltage. These results are associated with the nanocrystalline WC phase and sp(2)
clusters in carbon networks increased by ion bombardment enhanced with increasing
DC bias voltage. Consequently, the increase of sp(2) clusters containing WC
nanocrystalline in the carbon films is attributed to the improvement in the
physical and electrical properties.
PMID- 27483858
TI - Transparent Electrode for Si Heterojunction Photoelectric Devices.
AB - The transparent conductive oxide layers are of great interest in recent
researches because of their tunable properties which avail them to be used in
varieties of applications. The important and most widely used TCO materials such
as ITO and AZO films were prepared with three different layer thicknesses using
DC sputtering system. The structural, optical and electrical characteristics of
both ITO and AZO samples were analyzed and compared to reveal thickness dependent
tunable properties of TCO materials. The maximum transmittance of 99.5% was
obtained for AZO films at 600-700 nm wavelength range. The resistivity of ITO
films was 200 times lesser than that of AZO films. The internal and external
quantum efficiencies of ITO devices increased with increasing layer thickness
whereas this situation was just opposite in case of AZO devices. The optical and
electrical properties of ITO samples were found easily adjustable by changing
layer thickness as compared to AZO samples. This study explores the strong
association between the layer thickness and the properties of TCO films. This
would be useful to extend the applications boundary of TCO materials.
PMID- 27483859
TI - Gravure-Offset Printed Metallization of Multi-Crystalline Silicon Solar Cells
with Low Metal-Line Width for Mass Production.
AB - The gravure offset method has been developed toward an industrially viable
printing technique for electronic circuitry. In this paper, a roller type gravure
offset manufacturing process was developed to fabricate fine line for using front
electrode for solar cells. In order to obtain the optimum metallization printing
lines, thickness of 20 MUm which is narrow line is required. The main targets are
the reduction of metallized area to reduce the shading loss, and a high
conductivity to transport the current as loss free as possible out of the cell.
However, it is well known that there is a poor contact resistance between the
front Ag electrode and the n(+) emitter. Nickel plating was conducted to prevent
the increase of contact resistance and the increase of fill factor (FF). The
performance of n-Si/Ag (seed layer)/Ni solar cells were observed in 609 mV of
open circuit voltage, 35.54 mA/cm2 of short circuit current density, 75.75% of
fill factor, and 16.04% of conversion efficiency.
PMID- 27483860
TI - Improvement of Pre-Annealed Cu(In, Ga)Se2 Absorbers for High Efficiency.
AB - We used a DC-sputtering method to deposit the precursor (Cu3Ga/In) onto Mo with 1
um thick/soda-lime glass (SLG). We moved it onto a graphite crucible for the pre
annealing process, and the pressure of the process tube was about 10 torr without
Ar gas flow. The crucible in quartz tube was heated by halogen lamp to 250
degrees C for 30 min, and then raised to 550 degrees C for 10 min under a
selenium atmosphere. To complete the solar cells, a buffer layer of 50 nm CdS was
then deposited by chemical bath deposition (CBD), followed by a double layer
(high resistivity/low resistivity) of RF sputtered i-ZnO/Al-ZnO thin films. The
Al front contacts were deposited by thermal evaporator.
PMID- 27483861
TI - Improvement in the Photocurrent of Inverted Organic Solar Cells Using MoO(x)
Doped TAPC as a P-Type Optical Spacer.
AB - In this work, we demonstrate enhancement in the short-circuit current of inverted
organic photovoltaic cells (OPVs) using a p-type optical spacer. The p-type
optical spacer, which consists of molybdenum oxide (MoO(x))-doped 1,1-bis[(di-4
tolylamino)phenyl]cyclohexane (TAPC), shows improved transmittance at visible
light with high electrical conductivity. The electrical field distribution of
incident light at the active layer of OPVs can be controlled by tuning the
thickness of the optical spacer in the OPVs. Specifically, the incorporation of
the 20-nm optical spacer layer in the OPV leads to enhanced spectral response of
the device in the wavelength range of 400-600 nm, which is consistent with the
combined results of improved optical absorption and better charge transport
characteristics. As a result, the OPV with a 20-nm p-type optical spacer shows
improvement in the short-circuit current compared with a device with 10 nm of
embedded MoO(x).
PMID- 27483862
TI - Enhanced Haze Ratio on Glass by Novel Vapor Texturing Method.
AB - State-of-the-art optical trapping designs are required to enhance the light
trapping capabilities of tandem thin film silicon solar cells. The wet etch
process is used to texture the glass surface by dipping in diluted acidic
solutions such as HNO3 (nitric acid) and HF (hydrofluoric acid). For vapor
texturing, the vapor was generated by adding silicon to HF:HNO3 acidic solution.
The anisotropic etching of vapor textured wafers resulted in an etching depth of
about 2.78 MUm with reduced reflectance of 5%. We achieved a high haze value of
74.6% at a 540 nm wavelength by increasing the etching time and HF concentration.
PMID- 27483863
TI - Dibenzothiophene-Substituted Fullerene Derivative as Electron Acceptor for
Polymer Solar Cells.
AB - A new fullerene derivative, [6,6]-dibenzo[b,d]thiophene-C61-butyric acid methyl
ester (DBTC61BM) was synthesized from C60 using tosylhydrazone, and used as an
electron-acceptor material for poly(3-hexylthiophene) (P3HT)-based organic
photovoltaic cells. The synthesized DBTC61BM was used to modify the basic
structure of [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) by replacing the
aromatic part with dibenzo[b,d]thiophene. The solubilities of DBTC61BM and PC61BM
are similar; they have good solubilities in common organic solvents such as
dichloromethane, chloroform, toluene, and 1,2-dichlorobenzene. The Stern-Volmer
quenching constant (K(sv)) of DBTC61BM was 7.14 x 10(3) M(-1), and was correlated
with the binding affinity between the fluorophore and a quencher. The lowest
unoccupied molecular orbital energy level of DBTC61BM was -3.71 eV. The charge
carrier mobility of a P3HT:DBTC61BM blend film was determined using the space
charge-limited current method; the electron mobility value obtained for the
P3HT:DBTC61BM blend film was 2.13 x 10(-4) cm2 V(-1) s(-1). Photovoltaic devices
were fabricated using P3HT as the electron donor and DBTC61BM as the electron
acceptor. Among the fabricated devices, photovoltaic cells with the structure
ITO/PEDOT:PSS/P3HT:DBTC61BM/LiF/Al showed the highest power conversion
efficiency, namely 3.23%, with an open-circuit voltage of 0.64 V, short-circuit
current density of 8.14 mA cm(-2), and fill factor of 0.59, under AM 1.5 G (100
mW cm(-2)) illumination.
PMID- 27483864
TI - Patterning ITO by Template-Assisted Colloidal-Lithography for Enhancing Power
Conversion Efficiency in Organic Photovoltaic.
AB - Highly structured interfaces are very desirable in organic photovoltaic solar
cells (OPVs), in order to enhance power conversion efficiency (PCE) by decreasing
of the transport path for excited charge carriers in the absorber and increasing
the optical path length for photon absorption. Many complicated, high-cost
lithographic methods have been attempted to modify the surface of the absorber or
substrate. However, solution-based colloidal-lithography processes are scalable
and cost-effective, but generally result in non-uniform structured surfaces. In
this report, we demonstrated an optimized silica-templated colloidal
lithographical approach to create a well-defined and controlled transparent ITO
layer for enhancing power conversion efficiency (PCE). Additionally,
morphological effects of the patterned ITO on optical properties and PCE were
analyzed in detail.
PMID- 27483865
TI - Hydrogenated g-C4N3 for Metal-Free Photocatalysis: A First-Principles Study.
AB - Using the first principles method, we explored physical properties of
hydrogenated g-C4N3. We found that the vacany site became the most stable H
adsorption site. The electronic band structure and magnetic properties were
strongly affected by the H adsorption concentration. At low H concentration, the
g-C4N3 still preserved half metallic state. However, we observed a semiconducting
band gap at 14.3% H concentration and the magnetic state disappeared. Despite
this suppression of magnetic state, we found that the semiconducting H-g-C4N3
could be used for metal-free photocatalyst. The calculated band gap was 2.93 eV,
and this corresponds to an optical wavelength of 423 nm. The conduction band (CB)
edge was positioned at 1.54 eV higher in energy than H+/H2 level. This indicates
that it has a strong ability to reduce H+ to H2. At the same time, the valence
band (VB) edge position was 0.15 eV lower in energy than O2/H2O level. Overall,
we propose that the hydrogenated g-C4N3 can be used as a potential metal-free
photocatalytic material.
PMID- 27483866
TI - Chemical Amination via Cycloaddition of Graphene for Use in a Glucose Sensor.
AB - Graphene was chemically aminated via cycloaddition. Aziridine-ring linkages were
formed by covalently modifying the C-C double bonds in graphene. The aminated
graphene presents an enhanced hydrophilicity, the contact angle with water
decreases from 80.5 degrees to 58.5 degrees. And the conductivity of aminated
graphene exhibits exponential decay as the reaction time increase. If the
reaction time is 90 min, the resistance of aminated graphene was increased from
32 Omega to -2744 Omega. Because the amino group has good biocompatibility, the
aminated graphene is designed for use as an enzyme sensor platform, such as
glucose sensor based on glucose oxidase. The aminated graphene exhibited a good
detection response for glucose. The increase in device current is about 12% in
1.2 mg/mL glucose solution.
PMID- 27483867
TI - Design and Fabrication of Integrated Fabry-Perot Type Color Reflector for
Reflective Displays.
AB - A Fabry-Perot type integrated color reflector, with red/blue/green colors as
subpixels, was designed and fabricated with Si substrate. Ag films were used as
reflective mirror layers, SiO2 films were used as Fabry-Perot cavity layers and W
films were used as partially reflective layers for the cavity. To minimize the
effects of the thickness variation of the oxide cavity layers, the structure of
the color reflector was optimized, and the differential deposition scheme was
devised and applied in the fabrication process. The integrated color reflector
was successfully fabricated with the proposed fabrication scheme. The measured
white reflectance was > 45% in the visible spectrum range and -49% at 550 nm
wavelength. The fabricated reflector had moderate color gamut of 17% of the
National Television System Committee (NTSC) standard and it showed very high
white reflectivity. The fabricated color reflector is expected to be applicable
to reflective displays.
PMID- 27483868
TI - Dependence of Grain Size on the Performance of a Polysilicon Channel TFT for 3D
NAND Flash Memory.
AB - We investigated the dependence of grain size on the performance of a
polycrystalline silicon (poly-Si) channel TFT for application to 3D NAND Flash
memory devices. It has been found that the device performance and memory
characteristics are strongly affected by the grain size of the poly-Si channel.
Higher on-state current, faster program speed, and poor endurance/reliability
properties are observed when the poly-Si grain size is large. These are mainly
attributed to the different local electric field induced by an oxide valley at
the interface between the poly-Si channel and the gate oxide. In addition, the
trap density at the gate oxide interface was successfully measured using a charge
pumping method by the separation between the gate oxide interface traps and traps
at the grain boundaries in the poly-Si channel. The poly-Si channel with larger
grain size has lower interface trap density.
PMID- 27483869
TI - Performance of AlGaN/GaN Nanowire Omega-Shaped-Gate Fin-Shaped Field-Effect
Transistor.
AB - The AlGaN/GaN nanowire omega-shaped-gate FinFET have been successfully fabricated
demonstrating much improved performance compared to conventional AlGaN/GaN
MISHFET. The AlGaN/GaN omega-shaped-gate FinFET exhibited the remarkable on-state
performances, such as maximum drain current of 1.1 A/mm, low on-resistance, and
low current collapse compared to that of the conventional device structure. In
addition, the excellent off-state performances were measured: low off-state
leakage current as low as -10(-10) mA, the theoretical SS value of -62 mV/dec,
and high I(ON)/I(OFF) ratio (-10(9)). Improved dc performances were obtained for
omega-shaped-gate structure due to the fully depletion of the active fin body and
perfectly separation of the depleted fin from the underlying thick GaN buffer
layer. Furthermore, the additional reason for the enhanced device performance of
the proposed device is the improved gate controllability compared to the
conventional MISHFET. The proposed nano-structure device is very promising
candidate for the steep switching device applications.
PMID- 27483870
TI - Characteristics of Ga-Rich Cu(In, Ga)Se2 Solar Cells Grown on Ga-Doped ZnO Back
Contact.
AB - Wide bandgap Cu(In,Ga)Se2 (CIGS) thin films were deposited on Ga-rich Ga:ZnO
(GZO) or MoN/GZO by single-stage co-evaporation. CIGS/TCO interface phases, such
as resistive n-type Ga2O3, which are likely to have formed during the high
temperature growth of Ga-rich CIGS, can deteriorate the solar cell performance.
Although some Ga accumulation was observed in both of the CIGS/GZO and
CIGS/MoN/GZO interfaces formed at 520 degrees C, the Ga oxide layer was absent.
On the other hand, their current-voltage characteristics showed strong roll-over
behavior regardless of the MoN diffusion barrier. The strong Schottky barrier
formation at the CLGS/GZO junction due to the low work function of GZO, was
attributed to current blocking at a high forward bias.
PMID- 27483871
TI - Transparent Layer Derived from Layered Europium Hydroxide Sensitized with 2
Thenoyltrifluoroacetone.
AB - In this study, we present a novel layered material (LEuH-TTA) consisting of
layered europium hydroxide (LEuH) and organic sensitizer 2
thenoyltrifluoroacetone (TTA) in a simple and environmental benign way and it was
characterized by FT-IR and XRD. The luminescence intensity of LEuH-TTA increased
significantly after modified with TTA, almost 8 times that of LEuH at 612 nm. The
luminescence behavior of LEuH-TTA was investigated by luminescence analysis, the
results showed that red emission is caused by energy transfer from the TTA ligand
to the coordinated Eu3+ ions. Furthermore, the thickness of luminescence film was
measured and the SEM showed that it is about 1 MUm.
PMID- 27483872
TI - CO2 Capturing and Mineralization by (Mg)-Phyllosilicate Coated with Fabrics.
AB - To promote the practicality of magnesium (Mg)-phyllosilicate as a potent
carbonation agent, two inexpensive cotton and nylon fabrics are selected and
examined to assess their feasibility for use as supporting media of Mg
phyllosilicate. Mg-phyllosilicate is coated onto the fabrics via a sol-gel
method, whose mechanism is explained. The characteristics of the Mg
phyllosilicate coated cotton, along with those of the carbonation products, are
explored. Mg-phyllosilicate is found to mediate the carbon dioxide (CO2)
mineralization process actively, even on cotton of a supporting material.
Conclusively, the obtained results clearly support the potential of
mineralization as a feasible option for capturing CO2, in particular with the
abiotic catalyst of Mg-phyllosilicate coated onto flexible cotton.
PMID- 27483873
TI - Non-Stoichiometric Amorphous Indium Selenide Thin Films as a Buffer Layer for
CIGS Solar Cells with Various Temperatures in Rapid Thermal Annealing.
AB - The conventional structure of most of copper indium gallium diselenide (Culn(1
x)Ga(x)Se2, CIGS) solar cells includes a CdS thin film as a buffer layer. Cd-free
buffer layers have attracted great interest for use in photovoltaic applications
to avoid the use of hazardous and toxic materials. The RF magnetron sputtering
method was used with an InSe2 compound target to prepare the indium selenide
precursor. Rapid thermal annealing (RTA) was conducted in ambient N2 gas to
control the concentration of volatile Se from the precursor with a change in
temperature. The nature of the RTA-treated indium selenide thin films remained
amorphous under annealing temperatures of <= 700 degrees C. The Se concentration
of the RTA-treated specimens demonstrated an opposite trend to the annealing
temperature. The optical transmittance and band gap energies were 75.33% and
2.451-3.085 eV, respectively, and thus were suitable for the buffer layer. As the
annealing temperature increased, the resistivity decreased by an order-of
magnitude from 10(4) to 10(1) Omega-cm. At lower Se concentrations, the
conductivity abruptly changed from p-type to n-type without crystallite formation
in the amorphous phase, with the carrier concentration in the order of 10(17) cm(
3).
PMID- 27483874
TI - Optimization of CdS Buffer Layer for High Efficiency CIGS Solar Cells.
AB - In present work, effects of the thickness on the structural and optical
properties of chemically deposited CdS thin films were investigated. In addition,
we fabricated Cu(In, Ga)Se2 solar cells with various thicknesses of CdS buffer
layer and optimized the thickness for a high efficiency. When the CdS thin films
were thicker, the crystallinity improved but the transmittance decreased. The
short-circuit current density (J(sc)) and the fill factor are the major
efficiency limiting factors for the CIGS solar cells. As the thickness of the CdS
buffer layer, the open-circuit voltage (V(oc)) and the fill factor increased,
whereas the J(sc) slightly decreased. The improvement of the fill factor and thus
efficiency resulted from larger shunt resistance. For the solar cells without a
high resistive intrinsic ZnO layer, the highest efficiency was acquired at the
thickness of 89 nm. With further increasing the thickness, the J(sc) decreased
significantly, resulting in poor efficiency.
PMID- 27483875
TI - Characteristics of Sputtered ZnO Thin Films for an Inverted Organic Solar Cell.
AB - Several research groups have claimed high energy conversion efficiency in organic
solar cells. However, it still has low efficiency and is unstable, because
organic materials are easily oxidized by atmospheric humidity and UV light. In
this work, ZnO thin film as the blocking layer attributed to the interference of
the injection of the hole from the P3HT and no charge carrier recombination. We
obtained the maximum power conversion efficiency of 1.9% under AM 1.5 G spectral
illumination of 100 MWcm(-2), when we used a ZnO film of 60 nm and the optimized
P3HT:PCBM, and Au as the back electrode to solve the reaction problem of Al
electrode and to control the work function between the HOMO level of P3HT and the
energy level of the metal electrode. Power conversion efficiency of inverted
organic solar cell (IOSC) is significantly dependent on the thickness of the ZnO
thin film deposited by unbalanced magnetron sputtering method. Also, the
stability of IOSC is measured under ambient conditions.
PMID- 27483876
TI - Synthesis of CZTS Nanoparticles for Low-Cost Solar Cells.
AB - In this work, uniformly sized Cu2ZnSnS4 (CZTS) nanoparticles with easy control of
chemical composition were synthesized and printable ink containing CZTS
nanoparticles was prepared for low-cost-solar cell applications. In addition, we
studied the effects of synthesis conditions, such as reaction temperature and
time, on properties of the CZTS nanoparticles. For CZTS nanoparticles synthesis
process, the reactants were mixed as the 2:1:1:4 molar ratios. The reaction
temperature and time was varied from 220 degrees C to 320 degrees C and from 3
hours to 5 hours, respectively. The crystal structure and morphology of CZTS
nanoparticles prepared under the various conditions were investigated by X-ray
diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM), and
energy dispersive X-ray spectroscopy (EDS) was used for compositional analysis of
the CZTS nanoparticles.
PMID- 27483877
TI - Structural, Electrical, and Optical Properties of ZnO Film Used as Buffer Layer
for CIGS Thin-Film Solar Cell.
AB - The CuIn(x)Ga(1-x)Se2 (CIGS) using the solution-based fabrication method is
attractive for thin film solar cells because of its possibilities for large-area
and low-cost production. ZnO films between transparent conductive oxide (TCO) and
the CdS films can improve the performances of CIGS thin-film solar cells. In this
study, we investigated the characteristics of ZnO film between TCO and CIGS
layers in a solar cell (AZO/ZnO/CdS/CIGS/Mo), which were deposited at various
thicknesses to investigate the role of the films in CIGS solar cells. It was
confirmed that the conversion efficiency of a CIGS solar cell depends on the ZnO
film. For a ZnO film thickness of 80 nm, the highest power conversion efficiency
that a solar cell achieved was J(sc) of 18.73 mA/cm2.
PMID- 27483878
TI - DRAM Weak Cell Characterization for Retention Time.
AB - This work proposes a sequence of tests for detecting refresh weak cells based on
data retention time distribution in the main cell array of DRAMs and verify the
feasibility of the proposed method through analysis of 30 nm design-rule DRAM
cells with Recess Channel Array Transistor (RCAT) and Buried Channel Array
Transistor (BCAT). Basic idea of the proposed mechanism is to test with different
bias conditions and break down retention failures based on their root causes such
as Gate Induced Drain Leakage, sub-threshold leakage and junction leakage. This
categorization helps to determine the physical locations of each failure group,
enabling precise Physical Failure Analysis (PFA). The characterization of data
retention weak cells for 30 nm design rule DRAMs with BCAT and RCAT has been
investigated. Most weak cells were classified as GIDL leaky cells in both cases.
In the case of BCAT, the distance between the word line and the storage node,
caused by the process distribution, is the main origin of weak cells. In the case
of RCAT, the sharp corner of the active layer in the storage node is the main
cause of weak cells.
PMID- 27483879
TI - Electrical and Optical Properties of Hydrogen Doped Aluminum-Doped Zinc Oxide
Thin Films for Low Cost Applications.
AB - Aluminum-doped zinc oxide (AZO) thin films were prepared on glass substrate using
a magnetron sputtering system. In this work, a powder target was used as a source
material for low cost applications, instead of a conventional sintered ceramic
target. The effects of the hydrogen gas ratio on the electrical and optical
properties of the AZO films. The hydrogen doped AZO (AZO:H) films had a hexagonal
polycrystalline structure. A small amount of hydrogen gas deteriorated the
electrical and optical properties of the AZO:H films. However, these properties
improved, as the H2/(H2 + Ar) gas ratio increased. The AZO:H films grown at an
H2/(H2+Ar) ratio of 10% showed good properties for low cost applications, such as
a low resistivity of 1.35 x 10(-3) Omega-cm, high average transmittance of 83.1%
in the visible range of light.
PMID- 27483880
TI - Influence of Deposition Pressure on the Properties of Round Pyramid Textured a
Si:H Solar Cells for Maglev.
AB - HIT (Heterojunction with Intrinsic Thin-layer) photovoltaic cells is one of the
highest efficiencies in the commercial solar cells. The pyramid texturization for
reducing surface reflectance of HIT solar cells silicon wafers is widely used.
For the low leakage current and high shunt of solar cells, the intrinsic
amorphous silicon (a-Si:H) on substrate must be uniformly thick of pyramid
structure. However, it is difficult to control the thickness in the traditional
pyramid texturing process. Thus, we textured the intrinsic a-Si:H thin films with
the round pyramidal structure by using HNO3, HF, and CH3COOH solution. The
characteristics of round pyramid a-Si:H solar cells deposited at pressure of 500,
1000, 1500, and 2000 mTorr by PECVD (Plasma Enhanced Chemical Vapor Deposition)
was investigated. The lifetime, open circuit voltage, fill factor and efficiency
of a-Si:H solar cells were investigated with respect to various deposition
pressure.
PMID- 27483881
TI - Simultaneous Engineering of the Substrate Temperature and Mixing Ratio to Improve
the Performance of Organic Photovoltaic Cells.
AB - In this study, we investigated the effect of the donor/acceptor mixing ratio and
the substrate temperature (T(SUB)) during the co-deposition process on the
performance of bulk heterojunction organic photovoltaic cells. We found that the
ratio of dispersed donor islands (less than 10 nm), which hinders charge carrier
transport, increased as the donor concentration (C(D)) increased in the film
processed at room temperature. By contrast, the donor cluster (larger than 10
nm), providing percolation paths for the carriers, was enlarged in the film
containing a high C(D) fabricated at high T(SUB) (70 degrees C). This enhanced
phase separation in the mixed layer led to an improved fill factor and a
decreased activation energy of the short-circuit current (J(SC)). Therefore, we
demonstrated a 23% improvement in the device performance by employing an elevated
T(SUB) and optimized mixing ratio in comparison with the device fabricated at
room temperature.
PMID- 27483882
TI - Work Function Modification of Tungsten-Doped Indium Oxides Deposited by the Co
Sputtering Method.
AB - We have studied the work function modification of tungsten-doped indium oxides
(IWOs) through the co-sputtering of indium oxide (In2O3) and indium tungsten
oxide (In2O3 80 wt% + WO3 20 wt%) via a radio frequency (RF) magnetron sputtering
system. By controlling the elemental deposition of IWOs, the resultant work
functions varied from 4.37 eV to 4.1 eV. The IWO thin films showed excellent
properties for application as transparent conducting oxide materials in the
region of 0 to 2.43 at.% of tungsten versus the total metal content. The carrier
concentration of n-type IWO thin films varied from 8.39 x 10(19) cm(-3) to 8.58 x
10(21) cm(-3), while the resistivity varied from 3.15 x 10(-4) Omegacm to 2.26 x
10(-3) Omegacm. The largest measured optical band gap was 3.82 eV determined at
2.43 at.% of tungsten atoms relative to the total amount of metal atoms, while
the smallest optical band gap was 3.6 eV at 4.78 at.% of tungsten. IWO films
containing more than 2.43 at.% of tungsten atoms relative to the total number of
metal atoms revealed an average transmittance of over 80% within the visible
light region.
PMID- 27483883
TI - Effect of Reaction Temperature of CdS Buffer Layers by Chemical Bath Deposition
Method.
AB - This study investigated CdS deposition on a Cu(In,Ga)Se2 (CIGS) film via chemical
bath deposition (CBD) in order to obtain a high-quality optimized buffer layer.
The thickness and reaction temperature (from 50 degrees C to 65 degrees C) were
investigated, and we found that an increase in the reaction temperature during
CBD, resulted in a thicker CdS layer. We obtained a thin film with a thickness of
50 nm at a reaction temperature of 60 degrees C, which also exhibited the highest
photoelectric conversion efficiency for use in solar cells. Room temperature time
resolved photoluminescence (TR-PL) measurements were performed on the
Cu(In,Ga)Se2 (CIGS) thin film and CdS/CIGS samples to determine the recombination
process of the photo-generated minority carrier. The device performance was found
to be dependent on the thickness of the CdS layer. As the thickness of the CdS
increases, the fill factor and the series resistance increased to 61.66% and
decreased to 8.35 Omega, respectively. The best condition was observed at a
reaction temperature of 60 degrees C, and its conversion efficiency was 12.20%.
PMID- 27483884
TI - Rapid Annealing of Cu-In-Ga-Se Precursors by Electron Beam Irradiation Method.
AB - Cu-In-Ga-Se precursors were prepared by RF- and DC-sputtering methods and then
irradiated with an in-situ electron beam irradiation unit. Ternary (In,Ga)Se2 and
binary CuSe targets were simultaneously used for preparation of precursors. The
electron dose and irradiation time were kept constant at 300 seconds and 200 W of
RF power, respectively, while intensities of accelerated electrons were varied
from 2.5 to 4.5 keV. The thickness of all e-beam irradiated CuInGaSe2 (CIGS)
films decreased from 1,250 nm to 470 nm. The crystalline properties of e-beam
irradiated CIGS films were clearly shown on all samples and the highest intensity
of (112) peak at 3.5 keV. The compositional ratio of Cu/(In + Ga) in the e-beam
sample irradiated at 3.5 keV was coincident with that of the precursors. The
degree of Ga content on the depth of the e-beam sample irradiated at 3.5 keV was
uniformly distributed between the TCO/CdS layer and Mo back contact. Electron
beam irradiation onto Cu-In-Ga-Se precursors as a rapid annealing method could be
an excellent candidate for crystallization to the Cu(In,Ga)Se2 films.
PMID- 27483885
TI - Characterization of Flexible CIGS Thin Film Solar Cells or Stainless Steel with
Intrinsic ZnO Diffusion Barriers.
AB - ZnO diffusion barrier layer was deposited by RF magnetron sputtering by using the
same method as intrinsic ZnO layer. The CIGS solar cells were fabricated on
stainless steel substrate. The 50-200 nm thin ZnO diffusion barriers effectively
reduced the diffusion of Fe and Cr, from stainless steel substrates into the CIGS
absorbers. The CIGS solar cells with ZnO diffusion barriers increased the J(sc)
and FF, which resulted in an increase of cell efficiency from 5.9% up to 9.06%.
PMID- 27483886
TI - Amorphous Indium Selenide Thin Films Prepared by RF Sputtering: Thickness-Induced
Characteristics.
AB - The influence of indium composition, controlled by changing the film thickness,
on the optical and electrical properties of amorphous indium selenide thin films
was studied for the application of these materials as Cd-free buffer layers in
CI(G)S solar cells. Indium selenide thin films were prepared using RF magnetron
sputtering method. The indium composition of the amorphous indium selenide thin
films was varied from 94.56 to 49.72 at% by increasing the film thickness from 30
to 70 nm. With a decrease in film thickness, the optical transmittance increased
from 87.63% to 96.03% and Eg decreased from 3.048 to 2.875 eV. Carrier
concentration and resistivity showed excellent values of >=1015 cm(-3) and <=
10(4) Omega x cm, respectively. The conductivity type of the amorphous indium
selenide thin films could be controlled by changing the film-thickness-induced
amount of In. These results indicate the possibility of tuning the properties of
amorphous indium selenide thin films by changing their composition for use as an
alternate buffer layer material in CI(G)S solar cells.
PMID- 27483887
TI - Preparation of BaTiO3/Cu2O and BaTiO3/Cu2O/Au Complexes: Their Photocatalytic and
Antipathogenic Effect.
AB - BaTiO3/Cu2O and BaTiO3/Cu2O/Au complexes were prepared from CuCl2, HAuCl4
solution, and BaTiO3 by the solution method. BaTiO3 particles were dispersed in a
CuCl2 solution, and the BaTiO3/CuO complex was produced through crystallization
of CuO onto the BaTiO3 surface by hydrolysis of CuCl2 in the first stage. After
the reaction, CuO was reduced to Cu2O by treatment with glucose, thereby yielding
the BaTiO3/Cu2O complex. The BaTiO3/Cu2O/Au complex was prepared by treating the
BaTiO3/Cu2O particles with HAuCl4. Under visible light, the obtained
BaTiO3/Cu2O0/Au complex showed higher photocatalytic activity than the Degussa P
25sample. In addition, the BaTiO3/Cu2O complex showed excellent antipathogenic
effect.
PMID- 27483888
TI - Influence of Oxygen Gas Ratio on the Properties of Aluminum-Doped Zinc Oxide
Films Prepared by Radio Frequency Magnetron Sputtering.
AB - Aluminum-doped zinc oxide (AZO) thin films were deposited on glass and polyimide
substrates using radio frequency magnetron sputtering. We investigated the
effects of the oxygen gas ratio on the properties of the AZO films for
Cu(In,Ga)Se2 thin-film solar cell applications. The structural and optical
properties of the AZO thin films were measured using X-ray diffraction (XRD),
field emission scanning electron microscope (FE-SEM), and UV-Visible-NIR
spectrophotometry. The oxygen gas ratio played a crucial role in controlling the
optical as well as electrical properties of the films. When oxygen gas was added
into the film, the surface AZO thin films became smoother and the grains were
enlarged while the preferred orientation changed from (0 0 2) to (1 0 0) plane
direction of the hexagonal phase. An improvement in the transmittance of the AZO
thin films was achieved with the addition of 2.5-% oxygen gas. The electrical
resistivity was highly increased even for a small amount of the oxygen gas
addition.
PMID- 27483889
TI - Effects of Bias Pulsing on Etching of SiO2 Pattern in Capacitively-Coupled
Plasmas for Nano-Scale Patterning of Multi-Level Hard Masks.
AB - In order to study the effects of bias pulsing on the etching characteristics of a
silicon dioxide (SiO2) layer using multi-level hard mask (MLHM) structures of ArF
photoresist/bottom anti-reflected coating/SiO2/amorphous carbon layer (ACL)/SiO2,
the effects of bias pulsing conditions on the etch characteristics of a SiO2
layer with an ACL mask pattern in C4F8/CH2F2/O2/Ar etch chemistries were
investigated in a dual-frequency capacitively-coupled plasma (CCP) etcher. The
effects of the pulse frequency, duty ratio, and pulse-bias power in the 2 MHz low
frequency (LF) power source were investigated in plasmas generated by a 27.12 MHz
high-frequency (HF) power source. The etch rates of ACL and SiO2 decreased, but
the etch selectivity of SiO2/ACL increased with decreasing duty ratio. When the
ACL and SiO2 layers were etched with increasing pulse frequency, no significant
change was observed in the etch rates and etch selectivity. With increasing LF
pulse-bias power, the etch rate of ACL and SiO2 slightly increased, but the etch
selectivity of SiO2/ACL decreased. Also, the precise control of the critical
dimension (CD) values with decreasing duty ratio can be explained by the
protection of sidewall etching of SiO2 by increased passivation. Pulse-biased
etching was successfully applied to the patterning of the nano-scale line and
space of SiO2 using an ACL pattern.
PMID- 27483890
TI - Analysis of Stress Effect on (110)-Oriented Single-Gate SOI nMOSFETs Using a
Silicon-Thickness-Dependent Deformation Potential.
AB - The stress effect in uniaxially strained (100)- and (110)-oriented single-gate
(SG) silicon-on-insulator (SOI) n-type metal-oxide-semiconductor field-effect
transistors (MOSFETs) was analyzed. A model of a silicon-thickness-dependent
deformation potential (D(as_T(si))) was used for accurate calculation of mobility
using a Schrodinger-Poisson solver. The simulation results obtained using the
D(ac_T(si)) model exhibited excellent agreement with the measured mobility for
both strained and unstrained conditions. The enhancements in electron mobility
under conditions of longitudinal tensile strain were analyzed as a function of
the silicon thickness and strain. As the silicon thickness decreased, the
mobility enhancement in (100) SG MOSFETs reached a peak, whereas it diminished in
(110) SG MOSFETs. As the strain increased, mobility enhancement increased in the
(110) case, whereas it saturated in the (100) case. Therefore, larger mobility
enhancement in the (110) orientation is expected. These differences in
enhancement between the (100) and (110) cases resulted from differences in the
quantization mass, which affect the energy difference between the 1st subbands of
two-fold and four-fold degenerate valleys, as well as occupancy change.
PMID- 27483891
TI - InGaAs/InP Avalanche Photodiode for Single Photon Detection with Zinc Diffusion
Process Using Metal Organic Chemical Vapor Deposition.
AB - In this paper, we describe a design, simulation, and fabrication of an InGaAs/InP
single photon avalanche photodiode (SPAD), which requires a much higher gain,
compared to APD's for conventional optical communications. To achieve a higher
gain, an efficient multiplication width control is essential because it
significantly affects the overall performance including not only gain but also
noise characteristics. Normally, the multiplication layer width is controlled by
the Zinc diffusion process. For the reliable and controllable diffusion process,
we used metal organic chemical vapor deposition (MOCVD). The controllability of
the proposed diffusion process is proved by the diffusion depth measurement of
the fabricated devices which show the proportional dependence on the square root
of the diffusion time. As a result, we successfully implemented the SPAD that
exhibits a high gain enough to detect single photons and a very low dark current
level of about 0.1 nA with 0.95 breakdown voltage. The single photon detection
efficiency of 15% was measured at the 100 kHz gate pulse rate and the temperature
of 230 K.
PMID- 27483892
TI - Electrical Characteristics of Top-Gated Graphene Field Effect Transistors
Fabricated on Stainless Steel (STS) Substrate.
AB - Top-gated Graphene transistors with Al2O3 gate-dielectric on the flexible
stainless steel substrate have been demonstrated. Graphene was synthesized on
copper foil using a chemical vapor deposition method and transferred onto the
stainless steel substrate by wet transfer technique. The stainless steel
substrate was polished by chemical mechanical polishing method and the spin-on
glass layer was coated on the surface to improve the surface roughness. The
average surface roughness R(a) was as low as 5.9 nm from the AFM measurement. The
measured hole and electron mobilities from the current-voltage characteristics at
room temperature were calculated as high as 310 and 45 cm2/Vs, respectively. In
addition, the effect of surrounding temperature up to 355 K on the electrical
variations was investigated. The mobility was inversely proportional to the
temperature with negligible hysteresis where the temperature coefficient was
calculated as low as -0.65 %/K.
PMID- 27483893
TI - Multi-Bit Nano-Electromechanical Nonvolatile Memory Cells (Zigzag T Cells) for
the Suppression of Bit-to-Bit Interference.
AB - Multi-bit nano-electromechanical (NEM) nonvolatile memory cells such as T cells
were proposed for higher memory density. However, they suffered from bit-to-bit
interference (BI). In order to suppress BI without sacrificing cell size, this
paper proposes zigzag T cell structures. The BI suppression of the proposed
zigzag T cell is verified by finite-element modeling (FEM). Based on the FEM
results, the design of zigzag T cells is optimized.
PMID- 27483894
TI - Two-Step Growth of Epitaxial InP Layers by Metal Organic Chemical Vapor
Deposition.
AB - In this study, we report experimental results on the epitaxial growth of InP
layer on GaAs (001) substrate by using MOCVD. We have systematically controlled
nucleation steps in order to obtain InP epitaxial layers with high crystallinity
quality. The controlling parameters were flow ratio of V/IIIsources and
thicknesses of nucleation layer for nucleation steps. We successfully improved
the surface roughness and crystallinity of IIP epitaxial layers on GaAs
substrates.
PMID- 27483895
TI - Nano-Nucleation Characteristic of Cu-Ag Alloy Directly Electrodeposited on W
Diffusion Barrier for Microelectronic Device Interconnect.
AB - Cu-Ag alloy interconnect is promising for ultra-large-scale integration (ULSI)
microelectronic system of which device dimension keeps shrinking. In this study,
seedless electrodeposition of Cu-Ag alloy directly on W diffusion barrier as
interconnect technology is presented in respect of nano-nucleation control.
Chemical equilibrium state of electrolyte was fundamentally investigated
according to the pH of electrolyte because direct nano-nucleation of Cu-Ag alloy
on W surface is challenging. Chelation behavior of Cu2+ and Ag+ ions with citrate
(Cit) and ammonia ligands was dependent on the pH of electrolyte. The amount and
kind of Cu- and Ag-based complexes determine the deposition rate, size, elemental
composition, and surface morphology of Cu-Ag alloy nano-nuclei formed on W
surface.
PMID- 27483896
TI - Charge Carrier Transport Through the Interface Between Hybrid Electrodes and
Organic Materials in Flexible Organic Light Emitting Diodes.
AB - We investigated the electronic properties of composite-type hybrid transparent
conductive electrodes (h-TCEs) based on Ag nanowire networks (AgNWs) and indium
tin oxide (ITO). These h-TCEs were developed to replace ITO, and their mechanical
flexibility is superior to that of ITO. However, the characteristics of charge
carriers and the mechanism of charge-carrier transport through the interface
between the h-TCE and an organic material are not well understood when the h-TCE
is used as the anode in a flexible organic light-emitting diode (f-OLED). AgNWs
were spin coated onto polymer substrates, and ITO was sputtered atop the AgNWs.
The electronic energy structures of h-TCEs were investigated by ultraviolet
photoelectron spectroscopy. f-OLEDs were fabricated on both h-TCEs and ITO for
comparison. The chemical bond formation at the interface between the h-TCE and
the organic layer in f-OLEDs was investigated by X-ray photoelectron
spectroscopy. The performances of f-OLEDs were compared based on the analysis
results.
PMID- 27483897
TI - Effects of Precursor Concentration on Structural and Optical Properties of ZnO
Thin Films Grown on Muscovite Mica Substrates by Sol-Gel Spin-Coating.
AB - The structural and optical properties of the ZnO thin films grown on mica
substrates for different precursor concentrations were investigated. The surface
morphologies of all the samples indicated that they consisted of granular
structures with spherical nano-sized crystallites. The thickness of the ZnO thin
films increased significantly and the optical band gap exhibited a blue shift
with an increase in the precursor concentration. It is remarkable that the
highest I(NBE)/I(DLE) ratio was observed for the ZnO thin film with 0.8 M
precursor concentration, even though cracks formed on the surface of this film.
PMID- 27483898
TI - Synthesis, Morphology Control and Electromagnetic Wave Absorption Properties of
Electrospun FeCo Alloy Nanofibers.
AB - Recently, increasing interest has been focused on one-dimensional (1 D) magnetic
nanomaterials that have significant anisotropic electromagnetic parameters and
size effects that can be used to achieve improved shielding efficiency. In this
study, the simple, low-cost and scalable synthesis of FeCo nanofibers is
demonstrated by combining an electrospinning process with sequential thermal
treatment involving calcination in air followed by reduction in H2 atmosphere. A
citric acid has an influence on the morphology of the electrospun product. The as
spun precursor nanofibers are transformed into CoFe2O4 and FeCo phases through
the sequential thermal treatment while maintaining the fibrous shapes. To
evaluate the electromagnetic (EM) wave-absorbing abilities of the FeCo
nanofibers, epoxy matrix composites with the nanofibers are fabricated. The
composites show excellent EM wave absorption properties where the power loss of
the FeCo nanofibers increased to 20 GHz without any degradation.
PMID- 27483899
TI - Preparation and Characterization of Nanostructured Manganese Oxide for
Supercapacitors.
AB - Nanostructured manganese oxides were synthesized by a sol-gel method using
manganese acetate (MnAc2) and citric acid (C6H8O7,) as precursors, and
characterized by Brunauer-Emmett-Teller (BET) analysis, Barrett-Joyner-Halenda
(BJH), X-ray diffraction (XRD), scanning electron microscopy (SEM), and
transmission electron microscopy (TEM) techniques. The nano-rod structure of MnO2
developed gradually when the calcination temperature varied from 380 to 580
degrees C. As the pH increased, the pore size increased, while the specific
surface area decreased. The effects of the pH and calcination temperature on the
electrochemical properties of the nano-MnO2 electrode, including the
supercapacitive behavior, were investigated by cyclic voltammetry (CV) tests. The
tests were performed between 0 and 0.8 V versus Ag/AgCl in 1 M Na2SO4 electrolyte
at various scan rates (10-200 mVs(-1)). The specific capacitance of the SP-380
sample, prepared at pH 6, was equal to 269.3 Fg(-1). After 300 cycles,
approximately a 3.4% increase of the specific capacitance was measured,
confirming the excellent cyclability.
PMID- 27483900
TI - Morphology and Optical Properties of Bare and Silica Coated Hybrid Silver
Nanoparticles.
AB - Owing to their wide applications in the field of optoelectronics, photonics,
catalysis, and medicine; plasmonic metal nanoparticles are attaining considerable
interest nowadays. The optical properties of these metal nanoparticles depend
upon their size, shape, and surrounding medium. The present work studies the
morphology and optical properties of bare silver nanoparticles and silica coated
hybrid silver nanoparticles. Aqueous phase mediated synthesis and water-in-oil
microemulsion mediated synthesis are two different wet chemical routes employed
for nanosynthesis. Direct coating of silica is performed in water-in-oil
microemulsion on pre-synthesized silver nanoparticles using tetraethyl
orthosilicate as silica precursor. This study shows that using different wet
chemical routes the size of the synthesized nanoparticles could be tuned. In
addition, using reverse micelles as nanoreactors, the thickness of the silica
shell around the core silver nanoparticles could be significantly controlled.
Further, the optical properties of silver nanoparticles could be adjusted through
the size and the surface coating.
PMID- 27483901
TI - Carbon Nanomaterials Alter Global Gene Expression Profiles.
AB - Carbon nanomaterials (CNMs), which include carbon nanotubes (CNTs) and their
derivatives, have diverse technological and biomedical applications. The
potential toxicity of CNMs to cells and tissues has become an important emerging
question in nanotechnology. To assess the toxicity of CNTs and fullerenol
C60(OH)24, we in the present work used the budding yeast Saccharomyces
cerevisiae, one of the simplest eukaryotic organisms that share fundamental
aspects of eukaryotic cell biology. We found that treatment with CNMs, regardless
of their physical shape, negatively affected the growth rates, end-point cell
densities and doubling times of CNM-exposed yeast cells when compared to
unexposed cells. To investigate potential mechanisms behind the CNMs-induced
growth defects, we performed RNA-Seq dependent transcriptional analysis and
constructed global gene expression profiles of fullerenol C60(OH)24- and CNT
treated cells. When compared to non-treated control cells, CNM-treated cells
displayed differential expression of genes whose functions are implicated in
membrane transporters and stress response, although differentially expressed
genes were not consistent between CNT- and fullerenol C60(OH)24-treated groups,
leading to our conclusion that CNMs could serve as environmental toxic factors to
eukaryotic cells.
PMID- 27483902
TI - A Hydrostatic Bearing Test System for Measuring Bearing Load Using Magnetic-Fluid
Lubricants.
AB - This paper conducts a study on the design of a hydrostatic bearing test system.
It involves the determination of viscous properties of magnetic-fluid lubricants.
The load of a hydrostatic thrust bearing using a water-based magnetite nanofluid
of varying volume flow rate is measured under an applied external induction field
via the test system. Results reveal that the presence of nanoparticles in a
carrier liquid would cause an enhanced bearing load. Such an effect could be
further magnified by increasing the lubricant volume flow rate or the external
induction field strength.
PMID- 27483903
TI - Analysis of the Effect of Silicon with Nano-Size Surface Structure on an
Electrode Formed Using Screen Printing.
AB - In this paper, we report an investigation into the effects of the texturing size
of silicon on the efficiency of a screen-printed Si solar cell. To accomplish
this, we produced solar cells with various textured surfaces. The method we used
to produce these cells included methods such as anisotropic chemical etching
(texturing size of about 4 MUm) using a mixed solution of KOH and IPA, reactive
ion etching (texturing size of about 0.2 MUm), and Ag catalyzed etching
(texturing size of about 90 nm). The solar cells with an Ag-catalyzed etching
textured structure showed the lowest efficiency of 11.87%, with the highest
series resistance of 1.32 Omega. In the case of anisotropic chemical etching, the
solar cell had the best efficiency of 17.84%, with the lowest series resistance.
This means that the electrodes and silicon surfaces were not well-connected with
the nano-sized textured silicon surface. The results revealed that conventional
silver paste at an average of 1.6 MUm is unsuitable for nano-sized textured Si
solar cells.
PMID- 27483904
TI - Structural and Optical Properties of Sputtered Cadmium Telluride Thin Films
Deposited on Flexible Substrates for Photovoltaic Applications.
AB - Cadmium telluride (CdTe) is a photovoltaic technology based on the use of thin
films of CdTe to absorb and convert sunlight into electricity. In this paper,
polycrystalline CdTe thin films were deposited using radio frequency magnetron
sputtering onto flexible substrates including polyimide and molybdenum foil. The
structural and optical properties of the films grown at various sputtering
pressures were investigated using X-ray diffraction (XRD), field-emission
scanning electron microscope (FE-SEM), and UV/Nis/NIR spectrophotometry. The
sputtering pressure was found to have significant effects on the structural
properties, including crystallinity, preferential orientation, and
microstructure. Deterioration of the optical properties of CdTe thin films were
observed at high sputtering pressure.
PMID- 27483905
TI - Sintering and Microstructure of BaTiO3 Nano Particles Synthesized by Molten Salt
Method.
AB - In order to establish thinner dielectric layers in thick film electronic
components such as MLCC (Multilayer ceramic capacitor), BaTiO3 nanoparticles have
been utilized. However, studies on the synthesis of nanoparticles smaller than 20
nm, the characteristics of the BaTiO3 powder, and the powder's sintering are
lacking. Therefore, this paper aims to synthesize BaTiO3 particles smaller than
20 nm by using the molten salt method and evaluate the microstructure and
dielectric properties by varying the sintering temperature from 750 degrees C to
1200 degrees C. Through the molten salt method and by using KOH-KCl mixed salt,
20 nm BaTiO3 powder was synthesized at a low temperature of 150 degrees C.
Sintering the pellets formed from the synthesized 20 nm BaTiO3 nano powder led to
the observation of an unusual phenomenon where the particles grew to approximate
sizes below 850 degrees C where densification progressed. At sintering
temperatures above 950 degrees C, particles that expanded into rod shapes were
observed and these particles were identified to be unreacted TiO2 based on the
results of the EDX (Energy Dispersive X-ray Spectroscopy) analysis and phase
analysis results.
PMID- 27483906
TI - Thermally Induced Tensile Strain of Epitaxial Ge Layers Grown by a Two-Step e
Beam Evaporation Process on Si Substrates.
AB - We have investigated the thermally induced tensile strain in Ge-on-Si for use in
optical sources of interconnection systems. Epitaxial Ge layers were grown using
a two-step hetero-epitaxy at low and high temperatures. The as-grown Ge-on-Si was
then annealed for direct bandgap conversion. A tensile strain of 0.06% in the as
grown Ge increased to 0.31% after annealing at 850 degrees C. As the thermal
budget of this post-growth anneal was increased, the tensile strain of relaxed Ge
on-Si also increases and a Si-Ge alloy forms. Physical characterization indicates
a tunable tensile stain in Ge-on-Si can be realized using post-growth annealing,
which will allow for a wide range of frequencies in optical interconnections.
PMID- 27483907
TI - Self-Boosted Tunnel Field-Effect Transistor Using Nitride Charge Trapping Layer
for Low Supply Voltage Operation.
AB - Tunneling field-effect transistors (TFETs) have been studied as a candidate for
low-power device due to the remarkable subthreshold characteristics. However,
digital circuits composed of TFET have significantly large propagation delay
compared with the conventional MOSFET circuits because of small current
drivability and large gate-to-drain capacitance. In this work, the electrical
characteristics of the self-boosted TFETs with nitride charge trapping layer have
been studied using TCAD simulations. Trapped charges in the nitride layer improve
subthreshold characteristics and on-current (I(ON)) of both nTFET and pTFET
during gate bias sweep. In addition, the benefits of the self-boosted TFET
devices to low supply voltage system application are investigated. Energy
consumption and propagation delay of both conventional and self-boosted TFET
inverters are compared by the mixed-mode circuit simulation study. Energy
consumption is almost same but the propagation delay of the self-boosted TFET
inverter is reduced especially for ultra-low voltage operation where system delay
is increased dramatically.
PMID- 27483908
TI - Extraction of Distance Between Interface Trap and Oxide Trap from Random
Telegraph Noise in Gate-Induced Drain Leakage.
AB - This paper presents an analysis of the Random Telegraph Noise (RTN) of the Gate
Induced Drain Leakage (GIDL) of a Metal Oxide Semiconductor Field Effect
Transistor (MOSFET). The RTN data that was measured and analytical equations are
used to extract the values of the parameters for the vertical distance of the
oxide trap from the interface and of the energy level of the interface trap.
These values and equations allow for the distance r between the interface trap
and the oxide trap to be extracted. For the first time, the accurate field
enhancement factor gamma(F), which depends on the magnitude of the electric field
at the Si/SiO2 interface, was used to calculate the current ratio before and
after the electron trapping, and the value extracted for r is completely
different depending on the enhancement factor that is used.
PMID- 27483909
TI - Development of Multi-Degree-Of-Freedom Piezoelectric Energy Harvester Using
Interdigital Shaped Cantilevers.
AB - A piezoelectric vibration energy harvester with interdigital shaped cantilever
was developed by using silicon bulk micromachining technology. The proposed
energy harvester was designed to obtain multi degree-of-freedom (m-DOF). Most of
the piezoelectric vibration energy harvesters are comprised of mass-loaded
cantilever beams having several resonant frequencies. The second resonant
frequency of such a device has lower amplitude compared to its first resonant
frequency (fundamental frequency). Therefore, the interdigital shaped cantilever
has been proposed for multiple fundamental resonant frequencies. The fabricated
piezoelectric vibration energy harvester is composed of main cantilever (MC), sub
main cantilever (SMC), and secondary cantilevers (SC). MC surrounds SMC and SC
which have same dimension of 5600 x 800 x 10 MUm3. The fabricated piezoelectric
energy harvester can generate 51.4 mV(p-p) and 11 mV(p-p) of output voltages at
24.2 Hz and 33 Hz of its resonant frequencies by MC. Moreover, it can generate 8
mV(p-p) and 6.6 mV(p-p) of output voltages at 24.2 Hz and 33.2 Hz of its resonant
frequencies by SMC; and 364 mV(p-p) of output voltage at 33.6 Hz of its resonant
frequency by SC.
PMID- 27483910
TI - Influence of Number Fluctuation and Position Variation of Channel Dopants and
Gate Metal Grains on Tunneling Field-Effect Transistors (TFETs).
AB - The influence of number fluctuation and position variation on channel dopants and
gate metal grains on tunneling field-effect transistors (TFETs) have been
discussed in comparison with metal-oxide-semiconductor FETs (MOSFETs). Based on
the simulation results of randomly generated device samples, the shape of the
statistical threshold voltage (V(th)) distribution of TFETs associated with
individual variation sources such as random dopant fluctuation (RDF) and work
function variation (WFV) have been found to be significantly different than that
of MOSFETs. This analysis provides a detailed insight into the variation sources
related to underlying physics of TFETs.
PMID- 27483911
TI - Development and Operation of Dual-Mode Analyzers for Wireless Power
Consortium/Power Matters Alliance Wireless Power Systems.
AB - We have designed a protocol analyzer to be used in wireless power systems and
analyzed the operation of wireless chargers defined by standards of Qi of
Wireless Power Consortium (WPC) and Power Matters Alliance (PMA) protocols. The
integrated circuit (IC, or microchip) developed so far for wireless power
transmission is not easily adopted by chargers for specific purposes. A device
for measuring the performance of test equipment currently available is required
to transform and expand the types of protocol. Since a protocol analyzer with
these functions is required, we have developed a device that can analyze the two
protocols of WPC and PMA at the same time. As a result of our research, we
present a dual-mode system that can analyze the protocols of both WPC and PMA.
PMID- 27483912
TI - Surfactant Effect in Polypyrrole and Polypyrrole with Multi Wall Carbon Nanotube
Counter Electrodes: Improved Power Conversion Efficiency of Dye-Sensitized Solar
Cell.
AB - In our present study, polypyrrole-1 (PPy1), polypyrrole-2 (PPy2), and polypyrrole
2/multi wall carbon nanotube composite film (PPy2/MWCNT) were proposed as counter
electrodes (CEs) in dye-sensitized solar cells (DSSCs) to replace the precious Pt
CE. These films were fabricated on fluorine-doped tin oxide substrates by using a
facile electrochemical polymerization route, and served as CEs in DSSCs. It is
shown that the introduction of anionic surfactant, sodium dodecyl sulfate (SDS),
enhanced the catalytic activity, thus leading to an improvement in the
performance of PPy2. Further, introduction of MWCNT resulted in increase in
conversion efficiency of DSSCs with PPy2/MWCNT composite film. The Tafel and
electrochemical impedance analysis revealed that the PPy2 and PPy2/MWCNT CEs
prepared with anionic surfactant possessed more catalytic activity and lower
charge transfer resistance in comparison with PPy1 -based CE. This resulted in a
better conversion efficiency of 5.88% for PPy2/MWCNT-based DSSC under 1 sun
condition, reaching 86% of the DSSC based on reference Pt counter electrode
(6.86%). These results indicate that the composite film with high catalytic
properties for I3- reduction can potentially be used as the CE in a high
performance DSSC.
PMID- 27483913
TI - Use of Artificial Neural Network for the Simulation of Radon Emission
Concentration of Granulated Blast Furnace Slag Mortar.
AB - In this study, an artificial neural networks study was carried out to predict the
quantity of radon of Granulated Blast Furnace Slag (GBFS) cement mortar. A data
set of a laboratory work, in which a total of 3 mortars were produced, was
utilized in the Artificial Neural Networks (ANNs) study. The mortar mixture
parameters were three different GBFS ratios (0%, 20%, 40%). Measurement radon of
moist cured specimens was measured at 3, 10, 30, 100, 365 days by sensing
technology for continuous monitoring of indoor air quality (IAQ). ANN model is
constructed, trained and tested using these data. The data used in the ANN model
are arranged in a format of two input parameters that cover the cement, GBFS and
age of samples and, an output parameter which is concentrations of radon emission
of mortar. The results showed that ANN can be an alternative approach for the
predicting the radon concentration of GBFS mortar using mortar ingredients as
input parameters.
PMID- 27483914
TI - Characterization of a Fe-Based Soft Magnetic Alloy System with High Saturation
Magnetization.
AB - The ratios of Fe/Co and Fe/B in a ferromagnetic alloy system, Fe(87-x-y) Co(x)
Ti7 Zr6 By (x = 20, 30, and 40 at% and y = 2 and 4 at%), which was produced by
the melt-spinning technique in the form of thin ribbons, were investigated to
improve the saturation magnetization. The thermal properties T(x) were in the
range of 792.0 K to 838.0 K, and it decreased by decreasing Fe/Co ratio. In the
as-spun amorphous ribbons, the saturation magnetization and coercivity ranged
from 137.5 emu/g to 164.2 emu/g and from 0.027 Oe to 1.245 Oe, respectively. The
optimum Fe/Co ratio for the Fe(83-x) Co(x) Ti7 Zr6 B4 system was determined to be
64:36. In other words, the optimum system was Fe60 Co25 Ti7 Zr6 B2, which
exhibited robust soft magnetic properties, such as a low coercivity of 0.252 Oe,
and high saturation magnetization of 164.2 emu/g (1.55 T). Also, in this system,
magnetic properties such as the saturation magnetization and coercivity increased
with decreasing Fe/Co ratio.
PMID- 27483915
TI - Growth and Structural Characteristics of CuGaSe2 Films Fabricated from Metallic
Precursors Followed by an Elemental Se Reaction Process.
AB - We investigated the growth, structural and optical characteristics of CuGaSe2
thin films prepared with the selenium reaction. Metallic precursor layers from
Cu0:5Ga0.5 and Cu0.8Ga0.2 alloy targets were prepared on a sodalime glass
substrate by using DC magnetron sputtering, and then annealed to form CuGaSe2 in
a rapid thermal process (RTP) with selenium radicals generated by a thermal
cracker. The base and sputtering pressures were < 5 x 10(-7) Torr and 30 mTorr,
respectively. At ambient temperature, the precursors from the Cu0.5Ga0.5 and
Cu0.8Ga0.2 targets were deposited at the rates of 42 nm/min. and 45 nm/min.,
respectively. The film thicknesses were about 300 nm. Selenization was carried
out at different annealing temperatures of T(a) = 450 degrees C, 500 degrees C,
550 degrees C, and 600 degrees C for time periods of 15 min., 30 min., and 60
min. We found that high quality CuGaSe2 films of crystal grains (-1 MUm in dia.)
fabricated with a reaction using elemental Se at temperatures as low as 450
degrees C for 30 min. When T(a) <= 350 degrees C, the Se reaction was
insufficient to form CuGaSe2. However, the annealing time had little effect on
the formation of CuGaSe2 at T(a) >= 450 degrees C. For all the samples, the
photoluminescence (PL) emission was only from the donor-acceptor interband
transition D1A1 for all the composition ratios of the films [Ga]/[Cu] -1.
PMID- 27483916
TI - Low-Temperature Process for Atomic Layer Chemical Vapor Deposition of an Al2O3
Passivation Layer for Organic Photovoltaic Cells.
AB - Flexible organic photovoltaic (OPV) cells have drawn extensive attention due to
their light weight, cost efficiency, portability, and so on. However, OPV cells
degrade quickly due to organic damage by water vapor or oxygen penetration when
the devices are driven in the atmosphere without a passivation layer. In order to
prevent damage due to water vapor or oxygen permeation into the devices,
passivation layers have been introduced through methods such as sputtering,
plasma enhanced chemical vapor deposition, and atomic layer chemical vapor
deposition (ALCVD). In this work, the structural and chemical properties of Al2O3
films, deposited via ALCVD at relatively low temperatures of 109 degrees C, 200
degrees C, and 300 degrees C, are analyzed. In our experiment, trimethylaluminum
(TMA) and H2O were used as precursors for Al2O3 film deposition via ALCVD. All of
the Al2O3 films showed very smooth, featureless surfaces without notable defects.
However, we found that the plastic flexible substrate of an OPV device passivated
with 300 degrees C deposition temperature was partially bended and melted,
indicating that passivation layers for OPV cells on plastic flexible substrates
need to be formed at temperatures lower than 300 degrees C. The OPV cells on
plastic flexible substrates were passivated by the Al2O3 film deposited at the
temperature of 109 degrees C. Thereafter, the photovoltaic properties of
passivated OPV cells were investigated as a function of exposure time under the
atmosphere.
PMID- 27483917
TI - Effects of Plasma Treatment on Carbon Nanowalls Grown by Microwave Plasma
Enhanced Chemical Vapor Deposition.
AB - In this study, the effects of post-plasma treatment on synthesized carbon
nanowalls (CNWs) grown with a microwave were investigated. CNWs were synthesized
by microwave plasma enhanced chemical vapor deposition (PECVD), employing a
mixture of CH4 and H2 gases. The plasma treatment was done in different plasma
environments (O2 and H2) but under the same condition of synthesized CNWs. Raman
spectroscopy, field emission scanning electron microscopy (FE-SEM), energy
dispersive X-ray spectroscopy (EDS), and fourier transform infrared spectroscopy
(FT-IR) were used to analyze the effects of the post-plasma treatment on the
synthesized CNWs. After the H2 post-plasma treatment, no significant changes in
the appearance and characteristics of the CNWs were observed. After the O2 post
plasma treatment, on the other hand, the CNWs were etched at a rate of 18.05
nm/sec. The Raman analysis confirmed, however, that the structural changes in the
CNWs caused by the O2 post-plasma treatment were insignificant.
PMID- 27483918
TI - Reaction Gas Ratio Effect on the Growth of a Diamond Film Using Microwave Plasma
Enhanced Chemical Vapor Deposition.
AB - In this study, diamond films were prepared using the microwave plasma-enhanced
chemical vapor deposition (PECVD) system, which included a DC bias system to
enhance the nucleation of the films. The films were synthesized on Si wafers with
different ratios of methane (CH4) and hydrogen (H2) gases. We have studied the
effects of the CH4-to-H2 ratio on the structural and optical properties of
diamond films. The thickness and surface profile of the films were characterized
via field emission scanning electron microscopy (FE-SEM). Raman was used to
investigate the structural properties of the diamond films. The refractive
indexes as functions of the CH4-to-H2 ratio were measured using an ellipsometer.
The FE-SEM analysis showed that the 3 and 5 sccm CH4 created diamond films. The
Raman analysis indicated that a nanocrystalline diamond film was formed at 3
sccm; a general diamond film, at 5 sccm; and films similar to the a-C:H film, at
7 sccm. The ellipsometer measurement showed that the refractive index of the
synthesized diamond film was around 2.42 at 3 sccm. This value decreased as the
CH4 volume increased.
PMID- 27483919
TI - Optical Properties of Oxygen Plasma-Treated Carbon Nanowalls Grown on Glass
Substrates.
AB - In this paper, we investigated the effect of oxygen (02) plasma treatment on a
synthesized carbon nanowall (CNW). A microwave plasma-enhanced chemical vapor
deposition (PECVD) system was facilitated to grow CNWs on a glass, using a
mixture of CH4 and H2 gases. First, the CNWs were post-plasma-treated for
different treatment durations, and then their optical properties were analyzed.
In addition, the cross-sectional and planar images of the CNWs were examined via
field-emission scanning electron microscopy (FE-SEM) depending on the different
post-plasma-treatment durations. Then the structural characteristics were
analyzed via Raman spectroscopy, and the changes in the light transmittance
depending on the O2 plasma treatment durations were analyzed using UV-Vis
spectroscopy. The effects of the post-plasma treatments on the synthesized CNWs
were evaluated. The results confirmed that O2 gas is effective for plasma etching
of CNWs.
PMID- 27483920
TI - Properties of Dye-Sensitized Solar Cells Using Carbon Nanowall Counter
Electrodes.
AB - This research investigates plasma-treated and metal-coated carbon nanowalls
(CNWs) for use as counter electrodes of dye-sensitized solar cells (DSSCs). The
CNWs were synthesized on a fluorine-tin-oxide (FTO) glass substrate using the
microwave plasma-enhanced chemical vapor deposition (PECVD) system with methane
(CH4) gas. The post-plasma treatment was performed on the CNWs with hydrogen (H2)
plasma using PECVD, and the CNWs were sputter-coated with metal films using the
RF magnetron sputtering system with a four-inch tungsten (W) target. Then the
post-plasma-treated and metal-coated CNWs were used as counter electrodes for the
fabrication of the DSSCs. Field-emission scanning electron microscopy (FE-SEM)
was performed to obtain cross-sectional and planar images of the grown CNWs. The
energy conversion efficiencies of the DSSCs manufactured using the post-plasma
treated and metal-layer-coated CNWs as the counter electrodes were measured.
PMID- 27483921
TI - Effect of Perovskite Overlayers on TiO2 Electrodes in Perovskite-Sensitized Solar
Cells.
AB - In this paper, we have studied the effect of the thickness of a CH3NH3PbI3
perovskite overlayer on mesoporous TiO2 electrodes in perovskite solar cells. The
overlayers were prepared by spin coating PbI2 films on the electrodes, which were
subsequently exposed to a CH3NH3I/2-propanol solution. We controlled the
thickness of the perovskite overlayer by changing the PbI2 solution
concentration. The thicknesses of the overlayers spin-coated from 0.5, 0.75, 0.9,
and 1 M PbI2 solutions were approximately 179, 262, 316, and 341 nm,
respectively. Perovskite solar cells with an approximately 316-nm-thick overlayer
showed the highest efficiency of 9.11%. We conclude that optimization of the
perovskite overlayer thickness in the solar cell structure is necessary to
improve the cell efficiency.
PMID- 27483922
TI - Influence of Deposition Conditions on Properties of All Sputtered CdS/CdTe Thin
Film Solar Cells.
AB - The effects of deposition conditions, such as substrate temperature and CdCl2
post treatments, on the structural and optical properties of CdTe films were
investigated. In addition, CdS/CdTe thin-film solar cells were fabricated by an
all-sputtering process, and their photovoltaic characteristics were studied. The
CdTe films had a polycrystalline, cubic structure with a preferred orientation of
the [1 1 1] direction parallel to the substrate surface, regardless of the
substrate temperature. As the substrate temperature increased, the crystallinity
of CdTe films improved. The grain size of the CdTe films increased after CdCl2
post treatment. In addition, the optical band gap increased with the substrate
temperature. The conversion efficiency of the CdS/CdTe solar cell improved at
higher substrate temperatures. The maximum efficiency, 9.23%, was obtained at a
substrate temperature of 400 degrees C, with an open-circuit voltage (V(oc)) of
0.78 V, a short-circuit current density (J(sc)) of 20.4 mA/cm2, and a fill factor
of 0.58.
PMID- 27483923
TI - Surface Stabilized InP/GaP/ZnS Quantum Dots with Mg Ions for WLED Application.
AB - One of the most highlighted cadmium-free quantum dots (QDs), InP-based QDs, have
improved their optical properties. However, InP-based QDs have some practical
drawbacks, for example, stability, compared with CdSe-based QDs. Poor stability
of InP-based QDs yields critical problems, such as agglomeration and
photoluminescence quenching in light emitting diode (LED). It has to be solved
for applications and most research has focused on thick outer shells as an
effective solution. We introduced magnesium cations for improving stability of
InP-based QDs. We applied very small amounts of Mg cations as surface
stabilizers, as a result, stability of QDs is clearly improved. Then, QD based
LED chips also yield improved values including RA of 84.4, CCT of 3799 K, and
luminous efficiency of 129.57 Im/W, which are highly improved data compared with
our previous results.
PMID- 27483924
TI - Universal Verification Methodology Based Register Test Automation Flow.
AB - In today's SoC design, the number of registers has been increased along with
complexity of hardware blocks. Register validation is a time-consuming and error
pron task. Therefore, we need an efficient way to perform verification with less
effort in shorter time. In this work, we suggest register test automation flow
based UVM (Universal Verification Methodology). UVM provides a standard
methodology, called a register model, to facilitate stimulus generation and
functional checking of registers. However, it is not easy for designers to create
register models for their functional blocks or integrate models in test-bench
environment because it requires knowledge of SystemVerilog and UVM libraries. For
the creation of register models, many commercial tools support a register model
generation from register specification described in IP-XACT, but it is time
consuming to describe register specification in IP-XACT format. For easy creation
of register model, we propose spreadsheet-based register template which is
translated to IP-XACT description, from which register models can be easily
generated using commercial tools. On the other hand, we also automate all the
steps involved integrating test-bench and generating test-cases, so that
designers may use register model without detailed knowledge of UVM or
SystemVerilog. This automation flow involves generating and connecting test-bench
components (e.g., driver, checker, bus adaptor, etc.) and writing test sequence
for each type of register test-case. With the proposed flow, designers can save
considerable amount of time to verify functionality of registers.
PMID- 27483925
TI - Effects of Lithium Oxide Addition on Sintering Behavior and Electrical
Conductivity of Ce0.8Gd0.2O1.9 Ceramics Prepared by Commercial Powders.
AB - The densification behavior and electrical conductivity of Ce0.8Gd0.2O1.9 ceramics
with lithium oxide concentrations ranging from 0 to 7 mol% were investigated. The
sintered density was found to increase with increasing Li2O content up to 2 mol%
and then to decrease somewhat upon further Li20 addition. Dense Ce0.8Gd0.2O1.9
ceramics with 97% of the theoretical density could be obtained by sintering the
milled mixture with 2 mol% Li2O addition at 1250 degrees C for 5 h. The
conductivity of the 2 mol% Li2O-added specimen showed a maximum value of 4.99 x
10(-3) Omega(-1) x cm(-1) at 700 degrees C. Pure Ce0.8Gd0.2O1.9 ceramics needed
to be sintered at 1550 degrees C in order to obtain an equivalent theoretical
density and conductivity. The addition of Li2O was found to promote the sintering
properties and electrical conductivities of Gd2O3-doped CeO2.
PMID- 27483927
TI - Nanoporous Electrospun Fibrous Meshes: Size-Controlled Reverse Micelles Strategy.
AB - A simple and efficient method to fabricate size-controlled nanoporous-nanofibrous
meshes has been demonstrated by introducing and removing novel size-controllable
porogens, reverse micelles, on electrospun polymeric nanofibers. Poly(D,L
lactide) and reverse micelles composed of amphiphilic diblock copolymer,
poly(ethylene glycol) methyl ether-block-poly(epsilon-caprolactone), were first
dissolved in an acetone/chloroform (3:1, v/v) mixture and then electrospun into
nanofibers, followed by 70% EtOH post-treatment. During the post-treatment, the
reverse micelles were dissolved in 70% EtOH at room temperature thus separated
from the poly(D,L-lactide) nanofibers backbone, resulting in a nanoporous
nanofibrous structure. The pores on the nanofibers are size-controllable because
the sizes of the reverse micelles can be adjusted by varying the water content
inside them. The sizes of reverse micelles, which ranged from 100 nm to 700 nm,
are investigated by dynamic light scattering. The pores of various sizes on the
poly(D,L-lactide) nanofibers have areas ranging from 20 MUm2 to 80 MUm2 were
observed by field-emission scanning electron microscopy.
PMID- 27483926
TI - Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric
Nanoparticles: Towards Effective Delivery of Neuropeptides.
AB - Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L
pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and
certain central nervous system (CNS) disorders, including schizophrenia,
Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound
effects on the CNS. However, TRH's therapeutic activity is severely hampered
because of instability and hydrophilicity owing to its peptidic nature which
results into ineffective penetration into the blood brain barrier. In the present
study, we report the synthesis and stability studies of novel chitosan engineered
TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim
of such an encapsulation is to allow effective delivery of TRH in biological
systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out
manually in solution phase followed by its encapsulation using PLGA to form
polymeric nanoparticles (NPs) via nanoprecipitation technique. Different
parameters such as type of organic phase, concentration of stabilizer, ratio of
organic phase and aqueous phase, rate of addition of organic phase were
optimized, tested and evaluated for particle size, encapsulation efficiency, and
stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to
achieve positive surface charge rendering them potential membrane penetrating
agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were
characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom
Electron Microscopy (TEM) and Infra-red spectroscopic techniques.
PMID- 27483928
TI - Crystal Structure and Photocatalytic Activity of Al-Doped TiO2 Nanofibers for
Methylene Blue Dye Degradation.
AB - Al-TiO2 nanofibers were prepared using a sol-gel derived electrospinning by
varying the Al/Ti molar ratio from 0 to 0.73 to investigate the effect of Al
doping on the crystal structure and the photocatalytic activity of Al-TiO2 for
methylene blue (MB) degradation. XRD results indicated that as the Al/Ti molar
ratio rose, crystal structure of Al-TiO2 was changed from anatase/rutile
(undoped), anatase (0.07-0.18), to amorphous phase (0.38-0.73), which was
confirmed by XPS and Raman analysis. The degradation kinetic constant increased
from 7.3 x 10(-4) min(-1) to 4.5 x 10(-3) min(-1) with the increase of Al/Ti
molar ratios from 0 to 0.38, but decreased to 3.4 x 10(-3) min(-1) when the Al/Ti
molar ratio reached 0.73. The Al-TiO2 catalyst doped with 0.38 Al/Ti molar ratio
demonstrated the best MB degradation. Experimental results indicated that the Al
doping in Al-TiO2 was mainly attributed to the crystal structure of TiO2 and the
photocatalytic degradation of MB.
PMID- 27483931
TI - Applications of TiO2, ZnO and Ag Nanomaterials to Denim Fabric.
AB - In previous studies much research has reported the determination of applications
of TiO2 (rutile and anatase), ZnO and Ag nanomaterials onto various textile
surfaces, but in this study for the first time application to denim fabric and
testing of the finished fabric for antimicrobial activities of these
nanomaterials was investigated. The presence of nanoparticles on dyed denim
fabric surfaces was confirmed by Scanning Electron Microscope (SEM). The
nanomaterial-impregnated denim fabric (100% cotton) showed significant
antibacterial activity against Staphylococcus aureus, Escherichia coli and
Escherichia coli isolated from pasta. Additionally, the UV tests indicated
excellent improvement in the UV absorbing activity of the TiO2 (rutile and
anatase), ZnO and Ag nanomaterial-treated fabrics.
PMID- 27483930
TI - Polydopamine-Coated TiO2 Nanotubes for Selective Photocatalytic Oxidation of
Benzyl Alcohol to Benzaldehyde Under Visible Light.
AB - TiO2 nanotube arrays grown by anodization were coated with thin layers of
polydopamine as visible light sensitizer. The PDA-coated TiO2 scaffolds were used
as photocatalyst for selective oxidation of benzyl alcohol under monochromatic
irradiation at 473 nm. Benzaldehyde was selectively formed and no by-products
could be detected. A maximized reaction yield was obtained in O2-saturated
acetonitrile. A mechanism is proposed that implies firstly the charge carrier
generation in polydopamine as a consequence of visible light absorption.
Secondly, photo-promoted electrons are injected in TiO2 conduction band, and
subsequently transferred to dissolved O2 to form O*2- radicals. These radicals
react with benzyl alcohol and lead to its selective dehydrogenation oxidation
towards benzaldehyde.
PMID- 27483929
TI - Effects of Platinum Nanocolloid in Combination with Gamma Irradiation on Normal
Human Esophageal Epithelial Cells.
AB - Our previous study demonstrated that platinum nanocolloid (Pt-nc), combined with
lower-dose gamma irradiation at 3, 5, and 7 Gy significantly decreased
proliferation and accelerated apoptosis of the human esophageal squamous cell
carcinoma-derived cell line KYSE-70. The aim of the present study was to
determine, under the same conditions as our previous study where gamma rays
combined with Pt-nc were carcinostatic to KYSE-70 cells, if we could induce a
radioprotective or the radiation-sensitizing effect on the human normal
esophageal epithelial cells (HEEpiC). HEEpiC were treated with various Pt-nc
concentrations and then irradiated with various gamma-ray doses. The
proliferative status of HEEpiC was evaluated using trypan blue dye-exclusion and
WST-8 assays. The cellular and nucleic morphological features were determined
using crystal violet and Hoechst 33342 stainings, respectively. The intracellular
level of reactive oxygen species (ROS) in HEEpiC was evaluated with a nitro blue
tetrazolium (NBT) assay. The apoptotic status was detected with caspase-3, Bax,
and Bcl-2 by Western blotting. Either Pt-nc or gamma irradiation could inhibit
the growth of HEEpiC; however, their combined use exerted a significant
proliferation-inhibitory effect in a Pt-nc dose-dependent manner than gamma
irradiation alone. Pt-nc resulted in radiation sensitization rather than
radiation protection on HEEpiC in vitro similar to KYSE-70 cells, when Pt-nc was
administrated alone or combined with gamma irradiation. Thus, Pt-nc has an
inhibitory effect on cell proliferation, a facilitative effect on apoptosis, and
a certain degree of toxicity against HEEpiC.
PMID- 27483932
TI - Nano-Web Cobalt Modified Silica Nanoparticles Catalysts for Water Oxidation and
MB Oxidative Degradation.
AB - Dioxygen generating materials, using water as oxygen source, can be used as
catalysts in hypoxic environments. Cobalt(II) modified silica (SiO2@NPCo)
nanoparticles were synthesized through coordination of cobalt(II) ions with
nitrogen atoms from 2-acetylpyridine modified silica (SiO2@NP). The SiO2@NPCo
nanoparticles further reacted with 1,3,5-benzenetricarboxylic acids, forming
porous nano-web nanoparticles (SiO2@NPCoCOOH). The synthesized SiO2@NPCoCOOH
nanoparticles were demonstrated as better white LED light driven photochemical
catalysts for oxidation of water than individual nanoparticles (SiO2@NPCo).
Moreover, the SiO2@NPCoCOOH/water system could decrease the content of methylene
blue (MB) in solution and therefore, the nanoweb cobalt(II) modified silica
nanoparticles can be environmentally friendly catalysts for oxidative degradation
of MB, using water as the oxygen source.
PMID- 27483933
TI - Advances in Poly(4-aminodiphenylaniline) Nanofibers Preparation by
Electrospinning Technique.
AB - Polyaniline (PANI) nanofibers are drawing a great deal of interest from academia
and industry due to their multiple applications, especially in biomedical field.
PANI nanofibers were successfully electrospun for the first time by MacDiarmid
and co-workers at the beginning of the millennium and since then many efforts
have been addressed to improve their quality. However, traditional PANI prepared
from aniline monomer shows some drawbacks, such as presence of toxic (i.e.,
benzidine) and inorganic (salts and metals) co-products, that complicate polymer
post-treatment, and low solubility in common organic solvents, making hard its
processing by electrospinning technique. Some industrial sectors, such as medical
and biomedical, need to employ materials free from toxic and polluting species.
In this regard, the oxidative polymerization of N-(4-aminophenyl)aniline, aniline
dimer, to produce poly(4-aminodiphenylaniline), P4ADA, a kind of PANI, represents
an innovative alternative to the traditional synthesis because the obtained
polymer results free from carcinogenic and/or polluting co-products, and,
moreover, more soluble than traditional PANI. This latter feature can be
exploited to obtain P4ADA nanofibers by electrospinning technique. In this paper
we report the advances obtained in the P4ADA nanofibers electrospinnig. A
comparison among polyethylene oxide (PEO), polymethyl methacrylate (PMMA) and
polystyrene (PS), as the second polymer to facilitate the electrospinning
process, is shown. In order to increase the conductivity of P4ADA nanofibers, two
strategies were adopted and compared: selective insulating binder removal from
electrospun nanofibers by a rinsing tratment, afterwards optimizing the minimum
amount of binder necessary for the electrospinning process. Moreover, the effect
of PEO/P4ADA weight ratio on the fibers morphology and conductivity was
highlighted.
PMID- 27483934
TI - Characterization of Zn(O,S) Buffer Layers for Cu(In,Ga)Se2 Solar Cells.
AB - Zn(O,S) thin films were deposited using a ZnS target under Ar/O2 gases by radio
frequency magnetron sputtering. As the O2 concentration increased, the deposition
rates of the Zn(O,S) films decreased due to increase of O-. The crystalline
structure of Zn(O,S) was maintained at up to 0.6% O2, while the films became
unstable at the condition exceeding 0.8% O2. This was attributed to incomplete
nucleation and film growth on the substrate at the room temperature.
Additionally, optical emission spectroscopy analysis indicated that an increased
O- intensity at high O2 concentration was responsible for the slow deposition
rate and increased oxygen concentration of the films. X-ray diffraction and
scanning electron microscopy revealed the formation of a Zn(O,S) crystal
structure with partial substitution of O for S and uniform and dense grains of
the films. X-ray photoelectron spectroscopy showed that the Zn(O,S) films have a
uniform composition of each element and consisted of a mixed crystal structure of
Zn(O,S) with Zn-O bonding. Overall, the results of this study confirmed that
Zn(O,S) films deposited by radio-frequency sputtering using Ar/O2 gas at room
temperature can be applied to Cu(In,Ga)Se2 solar cells as a buffer layer.
PMID- 27483935
TI - Effects of Bending Radii on the Characteristics of Flexible Organic Solar Cells
Investigated by Impedance Analysis.
AB - Flexible organic solar cells (OSCs) were fabricated on an indium-tin-oxide
(ITO)/poly(ethylene terephthalate) (PET) substrate and were subjected to bending
tests with various bending radii. We observed that the photovoltaic properties of
the OSCs precipitously deteriorated at a bending radius <= 0.75 cm. In order to
investigate the effects of the bending test, the changes in the surface
morphology and the sheet resistance of the ITO-coated PET samples were
investigated, and the photovoltaic properties of bent and unbent OSCs were
evaluated. Thereafter, equivalent circuits for the OSCs were assumed and the
change in their parameters, such as resistance and capacitance, was observed.
PMID- 27483936
TI - Effects of Plasma Polymer Films and Their Deposition Powers on the Barrier
Characteristics of the Multilayer Encapsulation for Organic Devices.
AB - Organic electronic devices (OEDs) are quite suitable for use in flexible devices
due to their ruggedness and flexibility. A number of researchers have studied the
use of OEDs on flexible substrates in transparent, flexible devices in the near
future. However, water and oxygen can permeate through the flexible substrates
and can reduce the longevity of OEDs made from organic materials, which are weak
to moisture and oxygen. In order to prevent the degradation of the OEDs,
researchers have applied an encapsulation layer to the flexible substrates. In
this study, Al2O3/plasma polymer film/Al2O3 multi-layers were deposited on
polyethylene-naphthalate substrates through a combination of atomic layer
deposition and plasma-enhanced chemical vapor deposition (PECVD). The plasma
polymer film, which is located between the Al2O3 films, is deposited via PECVD
with the use of a tetrakis(trimethylsilyloxy)silane precursor. The power of the
plasma deposition varied from 10 to 50 W. The hydrophobicity of the plasma
polymer film surfaces was investigated by measuring the water contact angle. The
chemical structures of the plasma polymer films were measured via ex-situ Fourier
transform infrared analysis. The permeation curves of the various films were
analyzed by performing a calcium (Ca)-test.
PMID- 27483937
TI - Electrical and Optical Properties of Si-Incorporated a-C:H Films via the Radio
Frequency Plasma-Enhanced Chemical Vapor Deposition Method.
AB - The optical and electrical properties of silicon-incorporated hydrogenated
amorphous carbon (a-C:H:Si) films deposited via the radio frequency (RF) plasma
enhanced chemical vapor deposition (PECVD) method using a mixture of CH4, H2, and
SiH4 were observed. The silane gas whose ranged from 0 to 25 vol.% [SiH4/(SiH4 +
CH4) was fed into the reactor while the other deposition parameters were kept
constant. The basic properties of these films were investigated via Raman
spectroscopy, UV-visible spectrometry, I-V measurement, and surface profiling.
The experiment results showed that the film thickness increased from 300 nm to
800 nm for the same deposition time as the silane gas increased. The Raman
spectrum obtained from the silicon-incorporated a-C:H films suggested that the
film property changed from graphitic-like to more diamond-like. As the silane gas
increased, the optical gap, E04, slightly increased from 1.98 eV to 2.62 eV. It
was shown that the Si atoms incorporated into the a-C:H films reduced the size of
the sp2 clusters. As for the I-V characteristics, the Si-incorporated a-C:H films
had a lower leakage current than the a-C:H films without Si.
PMID- 27483938
TI - Optimization of the ZnS Buffer Layer by Chemical Bath Deposition for Cu(In,Ga)Se2
Solar Cells.
AB - We evaluated a ZnS buffer layer prepared using a chemical bath deposition (CBD)
process for application in cadmium-free Cu(In,Ga)Se2 (CIGS) solar cells. The ZnS
buffer layer showed good transmittance (above 90%) in the spectral range from 300
to 800 nm and was non-toxic compared with the CdS buffer layers normally used in
CIGS solar cells. The CBD process was affected by several deposition conditions.
The deposition rate was dependent on the ammonia concentration (complexing
agent). When the ammonia concentration was either too high or low, a decrease in
the deposition rate was observed. In addition, post heat treatments at high
temperatures had detrimental influences on the ZnS buffer layers because portions
of the ZnS thin films were transformed into ZnO. With optimized deposition
conditions, a CIGS solar cell with a ZnS buffer layer showed an efficiency of
14.18% with a 0.23 cm2 active area under 100 mW/cm2 illumination.
PMID- 27483939
TI - Crystallization Behavior of Amorphous Si3N4 and Particle Size Control of the
Crystallized alpha-Si3N4.
AB - Amorphous silicon nitride powder prepared by low-temperature vapor-phase reaction
was heat treated at various temperatures for different periods of time to examine
the crystallization behavior. The effects of the heat-treatment temperature and
duration on the degree of crystallization were investigated along with the effect
of the heat-up rate on the particle size, and its distribution, of the
crystallized alpha-phase silicon nitride powder. A phase transition from
amorphous to alpha-phase occurred at a temperature above 1400 degrees C. The
crystallization. process was completed after heat treatment at 1500 degrees C for
3 h or at 1550 degrees C for 1 h. The crystallization process starts at the
surface of the amorphous particle: while the outer regions of the particle become
crystalline, the inner part remains amorphous. The re-arrangement of the Si and N
atoms on the surface of the amorphous particle leads to the formation of
hexagonal crystals that are separated from the host amorphous particle. The
particle size and size distribution can be controlled by varying the heat
treatment profile (namely, the heat-treatment temperature, heating rate, and
heating duration at the specified temperature), which can be used to control the
relative extent of the nucleation and growth. The completion of most of the
nucleation process by lowering the heat-up rate can be used to achieve a singlet
particle size distribution. Bimodal particle size distribution can be achieved by
fast heat-up during the crystallization process.
PMID- 27483940
TI - Electrodeposition of Nanotwin Cu by Pulse Current for Through-Si-Via (TSV)
Process.
AB - Recently, the through-Si-via (TSV) had been focused as an optimal solution for
interconnecting the 3-dimensionaly stacked semiconductor devices. One of core
processes in the TSV technology is the Cu filling process which electrochemically
forms the Cu in the via with high aspect ratio. The nanotwin Cu is effective
candidate for replacing the conventional electrodeposited Cu due to its ultrahigh
mechanical strength and good electrical conductivity. In this work, the formation
of the nanotwin Cu in the TSV by applying pulse current was systematically
studied. Also, TSV filling behavior by electrodeposition with pulse current was
compared with direct current. The variation of mechanical properties as well as
the electrical resistivity of electrodeposited Cu by the pulse current also
investigated.
PMID- 27483941
TI - Extreme Ultraviolet Multilayer Defect Compensation in Computational Lithography.
AB - For the extreme ultraviolet (EUV) lithography, multilayer (ML) defects such as
bump and pit defects can disrupt the phase of reflected field and degrade aerial
images on wafer. In this paper, a defect printability and repair simulator (DPRS)
is introduced to predict and repair the effect of ML defects in EUV aerial
images. DPRS is composed of multilayer growth by using Gaussian function and
Stearns's method, mask simulation by using a scattering matrix (S-matrix)
analysis method, and projection simulation by using Kohler's illumination. For
bump and pit ML defects, the combining the modified absorber and the layer-by
layer ML peeling is better than other methods. This study can be helpful in
understanding EUV defect and also give insight into the EUV defect compensation
for the device volume production.
PMID- 27483942
TI - Assembly of Submicron Sized Ag, Co, and Ni Particles Into Thin Films at
Liquid/Liquid Interfaces.
AB - Submicron sized particles of Ag, Co and Ni were synthesised by reducing metal
salts in ethylene glycol (EG) in the presence of polyvinylpyrrolidone (PVP).
These particles on dispersion in water when held in contact with a toluene layer
were found to assemble into dense films extending over large areas at the
interface between the two liquids. The effect of reaction conditions (solvent,
precursor concentration, temperature) on the synthesis and assembly of the
particles was studied. The characteristics of the interfacial deposits and the
particulate dispersions were studied by scanning electron microscopy (SEM), X-ray
diffraction (XRD), ultraviolet-visible (UV-Vis) spectroscopy and dynamic light
scattering (DLS).
PMID- 27483943
TI - Silica Modified Chitosan/Polyethylenimine Nanogel for Improved Stability and Gene
Carrier Ability.
AB - Although chitosan-based hydrogel has been widely used as a gene carrier material,
further improvement in this aspect is still needed. Herein a new method was
proposed for preparing the effective chitosan-based gene carrier nanogel. The new
method based on the fact that supra-molecular interactions between silica,
polyethylenimine (PEI) and chitosan could be used to self-assemble them together
to form a rigid and stable gene carrier material in the reverse microemulsion
system. When compared with chemical cross-linking route, the proposed method is
simple and easy to adjust components of the resulting nanogel and, therefore, can
improve its gene carrying ability. Our results showed that, doping of the PEI and
silica into the chitosan hydrogel obviously increased its strength, stability and
gene carrying ability.
PMID- 27483944
TI - [Foreword].
PMID- 27483945
TI - [Epigenetic alterations and biological phenomena caused by mutation in an IDH
gene].
PMID- 27483946
TI - [Senescence-inducing stress and glycolytic enzyme, PGAM].
PMID- 27483947
TI - [Regulation of cellular energy metabolism by prolyl hydroxylase PHD].
PMID- 27483948
TI - [Post-transcriptional regulation and metabolism].
PMID- 27483949
TI - [Metabolic activation by a histone H3 lysine 36 demethylase, Fbxl10 in
leukemogenesis].
PMID- 27483950
TI - [Regulation of RNA methylation and epigeneticis effects by the ALKBH family].
PMID- 27483951
TI - [Molecular basis of tRNA methylthiolation and the pathological implications].
PMID- 27483952
TI - [Control of undifferentiated state by RB tumor suppressor].
PMID- 27483953
TI - [Hippocampus-synthesized androgens and estrogens enhance memory formation].
PMID- 27483954
TI - [Structure and function of glycolipids].
PMID- 27483955
TI - [Molecular dynamics and regulatory mechanisms for signals of glycosphingolipids
in membrane lipid rafts].
PMID- 27483956
TI - [Study on functional structures of artificial antibodies].
PMID- 27483957
TI - [Why Won't the Intractable MRSA Infections Go Away?].
PMID- 27483958
TI - [Structural basis of synaptic organizer complexes for inducing synapse formation
in the central nervous system].
PMID- 27483959
TI - [Methionine metabolism regulates biotransformation of glucose via protein
arginine methylation in cancer cells].
PMID- 27483960
TI - [N-glycans in the maintenance of stemness].
PMID- 27483961
TI - [Dynamic Recognition of Unfolded Proteins by the Trigger Factor Chaperone as
investigated by NMR].
PMID- 27483962
TI - [Host cholesterol biosynthesis as a potential target for anti-hepatitis C virus
strategies].
PMID- 27483963
TI - [Heterotrimeric G protein Gbetagamma subunits-regulated Rho family small G
protein-specific guanine nucleotide exchange factors].
PMID- 27483964
TI - [Pattern recognition receptor-mediated sensing mechanism during hepatitis virus
infection].
PMID- 27483965
TI - LONG-TERM THRIVERS.
PMID- 27483966
TI - HEALING THROUGH BARRIERS.
PMID- 27483967
TI - BEYOND OUR COMFORT ZONE.
PMID- 27483968
TI - TAINTED PASSION.
PMID- 27483969
TI - AMBASSADOR KATE.
PMID- 27483970
TI - GRINDR AND PrEP.
PMID- 27483971
TI - 'SOMETHING MORE IMPORTANT THAN FEAR'.
PMID- 27483972
TI - HEALTHCARE FORECASTING IN THE UNITED ARAB EMIRATES (UAE).
AB - This study has been designed to address the issue of the forecasting of the
healthcare needs of the United Arab Emirate (UAE) from 1974 to 2011. This
includes predicting the health system's need for hospitals and hospital beds, as
well as the public health manpower (example, physicians, nurses) requirements.
The analysis was based on historical data: the number of hospitals, number of
nurses, number of hospital beds, which have been posited as the measures of life
expectancy in the Emirate. The study found that, although significant changes
designed to enhance public health outcomes in the UAE have been made, beds to
population ratio was the most significant factor in enhancing healthcare and the
public health.
PMID- 27483973
TI - A POST ANALYSIS OF A PREVENTIVE AND CHRONIC HEALTHCARE TOOL.
AB - This study uses the data set from Kaiser Permanente to examine the post
implementation of a preventive and chronic care that utilizes clinical
information system, delivery system design, and clinical decision support to
maximize the office visit. The analysis suggests a significant positive
relationship between frequency of utilization rates to address preventive and
chronic care gaps. There is no implication of a significant positive relationship
with the successfully captured rate, which satisfies closing the care gap within
45 days. The use of the preventive care tool will assist members in satisfying
the preventive care gap, cervical cancer screening, within 45 days of the
encounter.
PMID- 27483974
TI - EARNINGS MANAGEMENT IN U.S. HOSPITALS.
AB - OBJECTIVE: This paper examines the hospital management practices of manipulating
financial earnings within the bounds of generally accepted accounting principles
(GAAP). STUDY DESIGN: We conduct regression analyses that relate earnings
management to hospital characteristics to assess the economic determinants of
hospital earnings management behavior. METHOD AND DATA: From the CMS Cost Reports
we collected hospital financial data of all U.S. hospitals that request
reimbursement from the federal government for treating Medicare patients, and
regress discretionary accruals on hospital size, profitability, asset liquidity,
operating efficiency, labor cost, and ownership. RESULTS: Hospitals with higher
profit margin, current ratio, working capital, days of patient receivables
outstanding and total wage are associated with more earnings management, whereas
those with larger size and higher debt level, asset turnover, days cash on hand,
fixed asset age are associated with lower level of earnings manipulation.
Additionally, managers of non-profit hospitals are more likely to undertake some
form of window-dressing by manipulating accounting accruals without changing
business models or pricing strategies than their public hospital counterparts.
CONCLUSIONS: We provide direct evidence of the use of discretionary accruals to
manage financial earnings among U.S. hospitals and the finding has profound
policy implications in terms of assessing the pervasiveness of accounting
manipulation and the overall integrity of financial reporting in this very
special public and quasi-public service sector.
PMID- 27483975
TI - COSTS OF DEPRESSION FROM CLAIMS DATA FOR MEDICARE RECIPIENTS IN A POPULATION
BASED SAMPLE.
AB - BACKGROUND: Many persons with depressive disorder are not treated and associated
costs are not recorded. AIMS OF THE STUDY: To determine whether major depressive
disorder (MDD) is associated with higher medical cost among Medicare recipients.
METHODS: Four waves of the Baltimore-Epidemiologic Catchment Area (Baltimore ECA)
Study conducted between 1981 and 2004 were linked to Medicare claims data for the
years 1999 to 2004 from the Centers for Medicare and Medicaid Services (CMS).
Generalized linear models specified with a gamma distribution and log link
function were used to examine direct medical care costs associated with MDD.
RESULTS: Medicare recipients with no history of MDD in either the ECA or CMS data
had mean six-year medical costs of US $40,670, compared to $87,445 for Medicare
recipients with MDD as recorded in CMS data and $43,583 for those with MDD as
recorded in Baltimore-ECA data. Multivariable regressions found that compared to
Medicare recipients with no history of depression, those with depression
identified in the CMS data had significantly higher medical costs; about 1.87
times (95% confidence interval (CI) 1.32 to 2.67) higher. Medicare recipients
with a history of depression identified in the ECA data were no more likely to
have higher costs than were Medicare recipients with no history of depression
(relative ratio 1.33, 95% CI 0.87 to 2.02). DISCUSSION: Medicare recipients with
a history of depression identified in claims data had significantly higher
medical costs than recipients with no history of depression. However, no
significant differences were found between Medicare recipients with depression in
the community-based Baltimore ECA data and those with no history of depression.
The results show that the source of diagnosis, in treatment versus survey data,
produces differences in results as regards costs. LIMITATIONS: This study
involved only Medicare recipients with claims data over the six years 1999 to
2004. Many of the ECA respondents were too young to qualify for Medicare.
IMPLICATIONS FOR HEALTH POLICY: Depressive disorder involves substantial medical
care costs. The findings provide information on the economic burden of
depression, an important but often omitted dimension and perspective of the
burden of mental illnesses.
PMID- 27483976
TI - QUANTITATIVE ASSESSMENT OF SOME PREVENTIVE HEALTH SERVICES PROVIDED FOR
ADOLESCENT INDIVIDUALS IN DUBAI.
AB - The United Arab Emirate (UAE) of Dubai, faces significant adolescent health
problems. In 2009, evidence based clinical guidelines were developed for primary
health care professionals in Dubai to help reduce adolescent health problems.
This research study explores adolescents' self-reports about health education
services received between 2008 and 2010. The sample consisted of 730 public high
school students in grades 10 through 12 between the ages of 15 and 19. 357
(48.9%) of the sample were males and 373 (51.1%) were female. The major language
spoken in the home was Arabic (77.4%). All students completed a 27-item survey in
Arabic that was adapted from the Young Adult Health Care Survey (YAHCS). The
YAHCS is a 56-item research instrument traditionally administered in English and
Spanish. The sample reported they had received little or no health education from
their health care providers. 94.2% reported receiving no information about using
a helmet for bicycle and motorbike safety; 88.2% reported receiving no
information about drug use; and 81.9% reported that they received no information
about smoking. The instrument also explored the health education material
students received within the last 12 months. 65.5% of the sample reported seeing
and/or hearing safety tips; 84.9% reported hearing and/or seeing health
information about healthy diet, physical activity and exercise; and 79.2%
reported seeing and/or hearing information about the risks of smoking and
substance abuse.
PMID- 27483977
TI - FACTORS ASSOCIATED WITH THE UPTAKE OF SODIUM DICHLOROISOCYANURATE (NADCC) TABLETS
AS HOUSEHOLD WATER-TREATMENT PRODUCT AMONG CAREGIVERS OF CHILDREN UNDER FIVE IN
BENIN, WEST AFRICA.
AB - Improving access to safe drinking water is a critical step in mitigating
diarrheal diseases that affect millions of children under 5 years throughout the
developing world each year. While the delivery of safe water is out of the reach
of many countries, the utilization of Sodium dichloroisocyanurate (NaDCC) is a
proven cost-effective alternative to prevent diarrhea caused by waterborne
pathogens. However, its uptake remains low in many developing countries, such as
the Republic of Benin. This study examines the trends and the determinants of
NaDCC uptake in Benin. Population Services International and its affiliate
conducted two multistage household surveys among caregivers of children under
five in Benin to examine the practices towards diarrheal disease in children
under five and identify the factors associated with the use of NaDCC in this
population. 2912 respondents/caregivers of children under five were interviewed
in 2009 versus 3196 in 2011. The proportion of caregivers who reported ever
treating water with NaDCC increased from 5.8% in 2009 to 11.5% in 2011, p <
0.001. The logistic regression model showed that caregivers who knew places that
sell NaDCC in the community; those who felt capable of utilizing NADCC correctly
to treat drinking water as well as caregivers who reported to be Muslim were more
likely than their counterparts to use NaDCC as water treatment product. In order
to increase the use of NADCC among caregivers, the Government of Benin and its
development partners should focus not only on making NADCC available in the
community and informing the community members about the different points of sale,
but also in building up the capacity and confidence of caregivers in utilizing
it.
PMID- 27483978
TI - AN OVERVIEW OF THE EFFICACY OF THE 12-STEP GROUP THERAPY FOR SUBSTANCE ABUSE
TREATMENT.
AB - This study was designed to determine if 12-Steps groups efficacy for substance
abuse treatment significantly improve abstinence rates of heroin addicts in the
short run and long run (1-year and 5-year period); and if abstinence rates are
found to be lower for heroin addicts that have attended 12-Step groups at the 1
year mark, and if similar results would be expected at the 5-year mark. Secondary
data from the Inter-University Consortium of Political and Social Research
(ICPSR) was extracted and analyzed for the aforementioned hypothesis. Using SSPS
to test the research hypothesis for the 1-Year Follow Up, the chi-square test
shows a p-value below of .10, and the analysis determined that there was
significant evidence to support the hypothesis that cases in a 12-Steps or self
help program have a higher success than cases not in a program for the 1-year
follow up. For 5-Year Follow Up, the cases that attended a 12-Step program or a
self-help program and about 27% went on to use heroin during the last 12 months
compared to 34% cases that did not go to a program.
PMID- 27483979
TI - The streamlined Allostatic Load Index: a replication of study results.
AB - According to the World Health Organization stress in the workplace is becoming a
major challenge of employers worldwide. While perceived stress levels can be
assessed by questionnaires there is growing evidence that stress-related wear and
tear of our body can be measured by the Allostatic Load Index (ALI). In a sample
of 12,477 German industrial employees (19.6% female, 18-65 years) self-rated
stress was explored by the effort-reward imbalance (ERI) questionnaire. A
voluntary health check included biomarkers such as diastolic blood pressure,
waist circumference, glycosylated hemoglobin, low-density lipoprotein, and heart
rate variability. Based on predefined subclinical cutoff values, a 5-variable ALI
was calculated. Differences in ALI according to low (ERI <=1.0) and high (ERI
>1.0) stress levels were tested. The association of ERI and ALI was explored
using logistic regression analysis controlling for multiple confounders.
Employees perceiving high stress levels showed significant higher ALI scores (p <
.001) compared to lower stressed employees. This association was stronger in men
and independent of age. ALI was associated with work stress in adjusted models
(OR 1.18 +/- .08 [95% CI 1.03, 1.36]; p < .05). This study replicates former
results in a large sample of industrial employees indicating that work stress is
associated with a short form ALI.
PMID- 27483980
TI - Business and Breakthrough: Framing (Expanded) Genetic Carrier Screening for the
Public.
AB - A growing body of research has given attention to issues surrounding genetic
testing, including expanded carrier screening (ECS), an elective medical test
that allows planning or expecting parents to consider the potential occurrence of
genetic diseases and disorders in their children. These studies have noted the
role of the mass media in driving public perceptions about such testing, giving
particular attention to ways in which coverage of genetics and genetic testing
broadly may drive public attitudes and choices concerning the morality, legality,
ethics, and parental well-being involved in genetic technologies. However, few
studies have explored how mass media are covering the newer test, ECS. Drawing on
health-related framing studies that have shown in varying degrees the impact
particular frames such as gain/loss and thematic/episodic can have on the public,
this study examines the frame selection employed by online media in its coverage
of ECS. This analysis-combined with an analysis of the sources and topics used in
such coverage and how they relate to selected frames-helps to clarify how mass
media are covering an increasingly important medical test and offers
considerations of how such coverage may inform mass media scholarship as well as
health-related practices.
PMID- 27483981
TI - Investigating a toxic risk (self-inflicted) the example of conventional and
advanced studies of a novel Tobacco Heating System.
AB - This special issue of Regulatory Toxicology and Pharmacology contains 9
scientific papers from Philip Morris International about the laboratory and 1
about early clinical investigation of a novel 'Tobacco Heating System'. The
studies have employed conventional and a wide range of newer 'omics and
bioinformatics techniques to seek and explore potential toxic actions of the
inhalable vapour it generates. The methods of study and display of results
employed are considered to be a valuable guide and model for wider application in
other toxicological investigations because they are directed more to proximal
causes of effects than to the cruder distal end points revealed by conventional,
empirical procedures. As such they should be regarded as a paradigm for the
applicability and accuracy of the testing and prediction of toxic risks.
PMID- 27483982
TI - Placental gene expression of the placental growth factor (PlGF) in intrauterine
growth restriction.
AB - OBJECTIVE: We analyzed changes in gene expression of placental growth factor
(PIGF) in human placental samples obtained postpartum from pregnancies with IUGR.
METHODS: During a twelve-month study period representing the calendar year of
2012 placental samples from 101 pregnancies with IUGR and from 140 normal
pregnancies were obtained for analysis of a potential difference in PIGF gene
expression. RESULTS: There was no significant difference in gene activity of the
PIGF gene between the IUGR versus normal pregnancy groups (Ln2alpha: 0.92; p <
0.06). Within the IUGR group, no fetal gender-dependent differences were seen in
placental PIGF gene expression (Ln2alpha: 0.72; p = 0.05). Placental PIGF gene
activity was significantly lower in fetuses with more severe IUGR versus less
severe cases (Ln2alpha: -1.49; p < 0.03). CONCLUSION: We found no difference in
gene expression of PIGF in placental samples obtained from IUGR pregnancies
versus normal pregnancy suggesting the absence of a direct role of PIGF gene
activity in the development of defective angiogenesis in IUGR during the later
stages of gestation. However, in more severe cases of intrauterine growth
restriction PIGF expression does show a significant decrease indicating its
potential role in the profound defect in angiogenesis in these cases.
PMID- 27483984
TI - Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation
Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing
Technology.
AB - Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing
tool. CRISPR/Cas9 has been well studied in model plant species for targeted
genome editing. However, few studies have been reported on plant species without
whole genome sequence information. Currently, no study has been performed to
manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II
CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome
repair, the 4'OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates
the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription,
viral-based TRV and synthetic binary plasmids were designed and delivered into
plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated
transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis.
Our results showed that the biosynthesis of BIAs (e.g. morphine, thebaine) was
significantly reduced in the transgenic plants suggesting that 4'OMT2 was
efficiently knocked-out by our CRISPR-Cas9 genome editing approach. In addition,
a novel uncharacterized alkaloid was observed only in CRISPR/Cas9 edited plants.
Thus, the applicabilitiy of the CRISPR/Cas9 system was demonstrated for the first
time for medicinal aromatic plants by sgRNAs transcribed from both synthetic and
viral vectors to regulate BIA metabolism and biosynthesis.
PMID- 27483985
TI - Bacterial repopulation of drinking water pipe walls after chlorination.
AB - The short-term kinetics of bacterial repopulation were evaluated after
chlorination of high-density polyethylene (HDPE) colonized with drinking water
biofilms and compared with bare HDPE surfaces. The effect of chlorination was
partial as a residual biofilm persisted and was time-limited as repopulation
occurred immediately after water resupply. The total number of bacteria reached
the same levels on both the bare and chlorinated biofilm-fouled HDPE after a
seven-day exposure to drinking water. Due to the presence of a residual biofilm,
the hydrophobicity of chlorinated biofilm-fouled surface exhibited much lower
adhesion forces (2.1 nN) compared to bare surfaces (8.9 nN). This could explain
the rapid repopulation after chlorination, with a twofold faster bacterial
accumulation rate on the bare HDPE surface. gamma-Proteobacteria dominated the
early stages of repopulation of both surfaces and a shift in the dominance
occurred over the colonization time. Such observations define a timescale for
cleaning frequency in industrial environments and guidelines for a rinsing
procedure using drinking water.
PMID- 27483986
TI - Autophagy promotes cell motility by driving focal adhesion turnover.
AB - In eukaryotic cells, cell migration is a dynamic and complex process that
involves finely tuned orchestration of a multitude of proteins including, for
example, those involved in focal adhesions (FAs). Cell migration plays an
indispensable role in particular stages of development and its proper regulation
is crucial in various biological processes, from wound healing to the immune
response. FAs are transmembrane protein complexes that traverse cytoskeletal
infrastructures all the way to the extracellular matrix, producing traction at
the leading edge of the cell, thus allowing for motility. The assembly of FAs has
been extensively studied, whereas disassembly remains poorly understood. Here, we
highlight 2 recent studies (see the corresponding puncta in the previous and
current issues of the journal) that demonstrate a requirement for
macroautophagy/autophagy in FA disassembly. These studies also provide a deeper
understanding of how autophagy can contribute to cell migration among multiple
cell types.
PMID- 27483987
TI - Modelling chronotaxicity of cellular energy metabolism to facilitate the
identification of altered metabolic states.
AB - Altered cellular energy metabolism is a hallmark of many diseases, one notable
example being cancer. Here, we focus on the identification of the transition from
healthy to abnormal metabolic states. To do this, we study the dynamics of energy
production in a cell. Due to the thermodynamic openness of a living cell, the
inability to instantaneously match fluctuating supply and demand in energy
metabolism results in nonautonomous time-varying oscillatory dynamics. However,
such oscillatory dynamics is often neglected and treated as stochastic. Based on
experimental evidence of metabolic oscillations, we show that changes in
metabolic state can be described robustly by alterations in the chronotaxicity of
the corresponding metabolic oscillations, i.e. the ability of an oscillator to
resist external perturbations. We also present a method for the identification of
chronotaxicity, applicable to general oscillatory signals and, importantly, apply
this to real experimental data. Evidence of chronotaxicity was found in
glycolytic oscillations in real yeast cells, verifying that chronotaxicity could
be used to study transitions between metabolic states.
PMID- 27483988
TI - Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and
Potential Hurdles.
AB - Hematopoietic stem and progenitor cells (HSPCs) have great therapeutic potential
because of their ability to both self-renew and differentiate. It has been
proposed that, given their unique properties, a small number of genetically
modified HSPCs could accomplish lifelong, corrective reconstitution of the entire
hematopoietic system in patients with various hematologic disorders. Scientists
have demonstrated that gene addition therapies-targeted to HSPCs and using
integrating retroviral vectors-possess clear clinical benefits in multiple
diseases, among them immunodeficiencies, storage disorders, and
hemoglobinopathies. Scientists attempting to develop clinically relevant gene
therapy protocols have, however, encountered a number of unexpected hurdles
because of their incomplete knowledge of target cells, genomic control, and gene
transfer technologies. Targeted gene-editing technologies using engineered
nucleases such as ZFN, TALEN, and/or CRISPR/Cas9 RGEN show great clinical
promise, allowing for the site-specific correction of disease-causing mutations-a
process with important applications in autosomal dominant or dominant-negative
genetic disorders. The relative simplicity of the CRISPR/Cas9 system, in
particular, has sparked an exponential increase in the scientific community's
interest in and use of these gene-editing technologies. In this minireview, we
discuss the specific applications of gene-editing technologies in human HSPCs, as
informed by prior experience with gene addition strategies. HSPCs are desirable
but challenging targets; the specific mechanisms these cells evolved to protect
themselves from DNA damage render them potentially more susceptible to
oncogenesis, especially given their ability to self-renew and their long-term
proliferative potential. We further review scientists' experience with gene
editing technologies to date, focusing on strategies to move these techniques
toward implementation in safe and effective clinical trials.
PMID- 27483990
TI - Potentiation of sprint cycling performance: the effects of a high-inertia
ergometer warm-up.
AB - Participant and protocol factors affect post-activation potentiation response.
Performance enhancement is more consistent in highly-trained participants
following multiple sets of a biomechanically similar conditioning activity.
Providing optimal conditions, 6 international-level sprint cyclists executed
multiple sets of short maximal conditioning contractions on a high-inertia
ergometer before metered sprint performance. Three trial conditions were
completed on separate days after a standardised warm-up: dynamic (DYN: 4 * 4
crank-cycles), isometric (ISO: 4 * 5-sec maximal voluntary contraction (MVC)),
and control (CON: rest). Performance was measured from standing start to maximum
velocity on an inertial-load ergometer at baseline (Pre), 4 (Post4), 8 (Post8)
and 16 (Post16) min post-conditioning. Performance and biomechanical measures
were assessed across 4 sprint segments, with magnitude-based inferences used to
assess the likelihood that any affect was beneficial. Performance time only
improved in DYN Post4, a 3.9% reduction during the first crank cycle (92%
likely). On the ascending limb of the power-cadence relationship, peak torque and
average power increased by 6.2% (94% likely) and 4.0% (87% likely), respectively.
In ISOPost16, optimal cadence increased (82% likely) and average power improved
over the descending limb (76% likely). DYN and ISO potentiated extremities of the
torque-cadence relationship at distinct recovery times post-conditioning. This
study suggests merit in including a high-inertia warm-up for sprint cycling.
PMID- 27483989
TI - Angiopoietin-like protein 2 expression is suppressed by angiotensin II via the
angiotensin II type 1 receptor in rat cardiomyocytes.
AB - The present study aimed to determine the inhibitory effects of angiotensin II
(AngII) on angiopoietin-like protein 2 (Angptl2) in rat primary cardiomyocytes,
and to investigate the potential association between angiotensin II type 1
receptor (AT1R) and these effects. Cardiomyocytes were isolated from 3-day-old
Wistar rats, and were cultured and identified. Subsequently, the expression
levels of Angptl2 were detected following incubation with various concentrations
of AngII for various durations using western blotting, reverse transcription
quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and
immunofluorescence. Finally, under the most appropriate conditions (100 nmol/l
AngII, 24 h), the cardiomyocytes were divided into six groups: Normal, AngII,
AngII + losartan, normal + losartan, AngII + PD123319 and normal + PD123319
groups, in order to investigate the possible function of AT1R in Angptl2
suppression. Losartan and PD123319 are antagonists of AT1R and angiotensin II
type 2 receptor, respectively. The statistical significance of the results was
analyzed using Student's t-test or one-way analysis of variance. The results
demonstrated that Angptl2 expression was evidently suppressed (P<0.05) following
incubation with 100 nmol/l AngII for 24 h. Conversely, the expression levels of
Angptl2 were significantly increased in the AngII + losartan group compared with
the AngII group (P<0.01). However, no significant difference was detected between
the AngII + PD123319, normal + losartan or normal + PD123319 groups and the
normal group. The present in vitro study indicated that AngII was able to
suppress Angptl2 expression, whereas losartan was able to significantly reverse
this decrease by inhibiting AT1R.
PMID- 27483991
TI - VivaScope(r) 1500 and 3000 systems for detecting and monitoring skin lesions: a
systematic review and economic evaluation.
AB - BACKGROUND: Skin cancer is one of the most common cancers in the UK. The main
risk factor is exposure to ultraviolet radiation from sunlight or the use of
sunbeds. Patients with suspicious skin lesions are first examined with a
dermoscope. After examination, those with non-cancerous lesions are discharged,
but lesions that are still considered clinically suspicious are surgically
removed. VivaScope((r)) is a non-invasive technology designed to be used in
conjunction with dermoscopy to provide a more accurate diagnosis, leading to
fewer biopsies of benign lesions or to provide more accurate presurgical margins
reducing the risk of cancer recurrence. OBJECTIVES: To evaluate the clinical
effectiveness and cost-effectiveness of VivaScope((r)) 1500 (Caliber Imaging and
Diagnostics, Rochester, NY, USA; Lucid Inc., Rochester, NY, USA; or Lucid Inc.,
MAVIG GmbH, Munich, Germany) and VivaScope((r)) 3000 (Caliber Imaging and
Diagnostics, Rochester, NY, USA) in the diagnosis of equivocal skin lesions, and
VivaScope 3000 in lesion margin delineation prior to surgical excision of
lesions. DATA SOURCES: Databases (MEDLINE, EMBASE and The Cochrane Library) were
searched on 14 October 2014, reference lists of included papers were assessed and
clinical experts were contacted for additional information on published and
unpublished studies. METHODS: A systematic review was carried out to identify
randomised controlled trials (RCTs) or observational studies evaluating
dermoscopy plus VivaScope, or VivaScope alone, with histopathology as the
reference test. A probabilistic de novo economic model was developed to
synthesise the available data on costs and clinical outcomes from the UK NHS
perspective. All costs were expressed as 2014 prices. RESULTS: Sixteen studies
were included in the review, but they were too heterogeneous to be combined in a
meta-analysis. One of two diagnostic studies that were deemed most representative
of UK clinical practice reported that dermoscopy plus VivaScope 1500 was
significantly more sensitive than dermoscopy alone in the diagnosis of melanoma
(97.8% vs. 94.6%; p = 0.043) and significantly more specific than dermoscopy
alone in the diagnosis of non-melanoma (92.4% vs. 26.74%; p < 0.000001). The
results of another study suggest 100% [95% confidence interval (CI) 86.16% to
100%] sensitivity for dermoscopy plus VivaScope 1500 versus 100% (95% CI 91.51%
to 100%) for dermoscopy alone. Specificity varied from 51.77% to 80.2% depending
on the analysis set used. In terms of margin delineation with VivaScope, one
study found that 17 out of 29 patients with visible lentigo maligna (LM) had
subclinical disease of > 5 mm beyond the dermoscopically identified margin. Using
'optimistic' diagnostic data, the economic model resulted in an incremental cost
effectiveness ratio (ICER) of L8877 per quality-adjusted life-year (QALY) (L9362
per QALY), while the 'less favourable' diagnostic data resulted in an ICER of
L19,095 per QALY (L25,453 per QALY) in the diagnosis of suspected melanomas.
VivaScope was also shown to be a dominant strategy when used for the diagnostic
assessment of suspected basal cell carcinoma (BCC). Regarding margin delineation
of LM, mapping with VivaScope was cost-effective, with an ICER of L10,241 per
QALY (L11,651 per QALY). However, when VivaScope was used for diagnosis as well
as mapping of LM, then the intervention cost was reduced and VivaScope became a
dominant strategy. LIMITATIONS: There is an absence of UK data in the included
studies and, therefore, generalisability of the results to the UK population is
unclear. CONCLUSIONS: The use of VivaScope appears to be a cost-effective
strategy in the diagnostic assessment of equivocal melanomas and BCCs, and in
margin delineation of LM prior to surgical treatment. FUTURE WORK: High-quality
RCTs are required in a UK population to assess the diagnostic accuracy of
VivaScope in people with equivocal lesions. STUDY REGISTRATION: This study is
registered as PROSPERO CRD42014014433. FUNDING: The National Institute for Health
Research Health Technology Assessment programme.
PMID- 27483992
TI - Development and characterization of repellent formulations based on
nanostructured hydrogels.
AB - Diseases caused by insects could lead to epidemic scenarios in urban areas and
insect repellents are a shield against a wide range of insects, but they need to
be safe without compromising efficacy. Ethyl butylacetylaminopropionate (EB) is a
synthetic mosquito repellent, which could be used in products for adults and
children due to its low-allergenic potential. The aim of this study was to
develop and characterize EB and Poloxamer 407 nanoemulsions regarding their
droplets mean size, pH, rheological properties, cytotoxicity and in vitro
permeation profile. The developed formulations (F1 with 12.5% of EB and F2 with
25% of EB) were compared with a commercial formulation containing 12.5% of EB.
Droplets mean size was determined by DLS, and for both nanoemulsions they were
around 200 nm; however, the commercial formulation presented a droplets mean size
of 10 nm, which could contribute to its high permeation. F1 and F2 presented a
gel-like behavior, however F2 presented lower viscosity due to the presence of
more EB between the polymer chains preventing them to interact with each other.
Also, F2 was less retained by the epidermis when compared to F1 probably due to
its lower viscosity. For the cytotoxicity assay only F2, which presented the
highest concentration of EB was tested, and it was not toxic to the cells. This
result could be also extended to F1 which presented half the EB concentration.
The present study demonstrated that EB and Poloxamer 407 nanoemulsions are
promising as new insect-repellent formulations.
PMID- 27483993
TI - Cost and impact of policies to remove and reduce fees for obstetric care in
Benin, Burkina Faso, Mali and Morocco.
AB - BACKGROUND: Across the Africa region and beyond, the last decade has seen many
countries introducing policies aimed at reducing financial barriers to obstetric
care. This article provides evidence of the cost and effects of national policies
focussed on improving financial access to caesarean and facility deliveries in
Benin, Burkina Faso, Mali and Morocco. METHODS: The study uses a comparative case
study design with mixed methods, including realist evaluation components. This
article presents results across 14 different data collection tools, used in 4-6
research sites in each of the four study countries over 2011-13. The methods
included: document review; interviews with key informants; analysis of secondary
data; structured extraction from medical files; cross-sectional surveys of
patients and staff; interviews with patients and observation of care processes.
RESULTS: The article finds that the policies have contributed to continued
increases in skilled birth attendance and caesarean sections and a narrowing of
inequalities in all four countries, but these trends were already occurring so a
shift cannot be attributed solely to the policies. It finds a significant
reduction in financial burdens on households after the policy, suggesting that
the financial protection objectives may have been met, at least in the short
term, although none achieved total exemption of targeted costs. Policies are
domestically financed and are potentially sustainable and efficient, and were
relatively thoroughly implemented. Further, we find no evidence of negative
effects on technical quality of care, or of unintended negative effects on
untargeted services. CONCLUSIONS: We conclude that the policies were effective in
meeting financial protection goals and probably health and equity goals, at
sustainable cost, but that a range of measures could increase their effectiveness
and equity. These include broadening the exempted package (especially for those
countries which focused on caesarean sections alone), better calibrated payments,
clearer information on policies, better stewardship of the local health system to
deal with underlying systemic weaknesses, more robust implementation of
exemptions for indigents, and paying more attention to quality of care,
especially for newborns.
PMID- 27483994
TI - The impact of differences between subjective and objective social class on life
satisfaction among the Korean population in early old age: Analysis of Korean
longitudinal study on aging.
AB - BACKGROUND: Several previous studies have established the relationship between
the effects of socioeconomic status or subjective social strata on life
satisfaction. However, no previous study has examined the relationship between
social class and life satisfaction in terms of a disparity between subjective and
objective social status. OBJECTIVE: To investigate the relationship between
differences in subjective and objective social class and life satisfaction.
METHODS: Data from the Korean Longitudinal Study of Aging with 8252 participants
aged 45 or older was used. Life satisfaction was measured by the question, "How
satisfied are you with your quality of life?" The main independent variable was
differences in objective (income and education) and subjective social class,
which was classified according to nine categories (ranging from high-high to low
low). This association was investigated by linear mixed model due to two waves
data nested within individuals. RESULTS: Lower social class (income, education,
subjective social class) was associated with dissatisfaction. The impact of
objective and subjective social class on life satisfaction varied according to
the level of differences in objective and subjective social class. Namely, an
individual's life satisfaction declined as objective social classes decreased at
the same level of subjective social class (i.e., HH, MH, LH). In both dimensions
of objective social class (education and income), an individual's life
satisfaction declined as subjective social class decreased by one level (i.e.,
HH, HM, HL). CONCLUSION: Our findings indicated that social supports is needed to
improve the life satisfaction among the population aged 45 or more with low
social class. The government should place increased focus on policies that
encourage not only the life satisfaction of the Korean elderly with low objective
social class, but also subjective social class.
PMID- 27483995
TI - The chaotic journey: Recovering from hip fracture in a nursing home.
AB - PURPOSE OF THE STUDY: To understand the journey experienced by nursing home
residents following hip fracture and impressions of an outreach rehabilitation
program offered after their return home. DESIGN AND METHODS: A qualitative
investigation was undertaken in parallel with a randomised controlled trial
investigating the efficacy and cost utility of providing a hospital outreach
rehabilitation program for older nursing home residents who have recently
returned from hospital following hip fracture. Family members and nursing home
staff of 28 (out of the first 30) participants (14 from intervention and 14 from
control) agreed to participate in interviews and focus groups to provide
information and perceptions of each person's journey. NVivo 10 qualitative data
analysis software package was used to identify major themes (via open, then axial
and finally selective coding). RESULTS: Both family members and staff described
nursing home residents with dementia as receiving poor post-operative care from
hospital staff who seemed unfamiliar with dementia and delirium. Discharge from
hospital soon after surgery (median 4.5days) occurred with poor transfer of
information. Difficulties with residents' emotions, pain management and
commencing mobilisation seemed more prevalent within usual care group, whereas
fewer overall problems were encountered by those with access to a geriatrician
and additional therapy. IMPLICATIONS: This research suggests that an integrated
care pathway including the hospital stay and first weeks back at nursing homes
should be developed. Performance indicators should include carer measures on the
quality of the transfer, pain management measures in the first month and return
to walking.
PMID- 27483996
TI - Diagnosed diabetes mellitus and in-hospital stroke mortality in a major sub
Saharan African urban medical unit.
AB - BACKGROUND: Estimates from developed countries show that early mortality after
stroke is unaffected by diabetes status. Despite the high burden of both
conditions in sub-Saharan Africa, data on the association between diabetes status
and early mortality are lacking. OBJECTIVE: In a major referral hospital in the
Capital city of Cameroon, among acute stroke patients diagnosed using the World
Health Organization criteria, we compared mortality rates in patents with and
without known diabetes. METHODS: Stroke patients with and without known diabetes
were compared for demographic characteristics, risk factors, clinical,
radiological, laboratory characteristic, and in-hospital mortality.
Heterogeneities in mortality rates across major subgroups were investigated via
interaction tests, and logistic regression accelerated failure-time models used
to adjust for confounders. RESULTS: Of the 1667 acute stroke patients included,
213 (12.8%) had diabetes mellitus. In general diabetic patients were older
(median age 64.0 vs. 62.0 years, p=0.0006), and were more likely to have other
stroke risk factors including a higher triglyceride levels on admission (106 vs.
97mg/dL, p=0.044), a history of stroke (19.7% vs. 13.6%, p=0.022), and a history
of hypertension (89.7% vs. 64.8%, p<0.0001). The death rates of diabetic patients
and that of non-diabetic patients were similar (22.1% vs. 20.1%. p=0.524). This
finding was similar across all pre-specified groups, with no evidence of
interaction. Diabetes was unrelated with mortality in adjusted regression models.
CONCLUSION: Diabetes is frequent among stroke patients in this setting, and often
co-exists with other stroke risk factors. In-hospital mortality rate is equally
high in diabetic and non-diabetic patients.
PMID- 27483997
TI - Membership in a diabetes-care network and adherence to clinical practice
guidelines for treating type 2 diabetes among general practitioners: A four-year
follow-up.
AB - OBJECTIVES: To assess whether private general practitioners (GPs) belonging to a
diabetes-care network adhered more closely to clinical practice guidelines for
diabetes care than GPs not in such a network, for all their patients with type 2
diabetes treated with medication (patients with diabetes), regardless of whether
they received care through a network (that is, whether a halo effect occurred).
RESEARCH DESIGN AND MEASURES: The study, based on health insurance reimbursement
databases in southeastern France, included 468 GPs in two networks and 468 non
network GPs in the same geographical area, matched one-to-one by propensity
scores. We followed up their patients with diabetes (n=22,808) from 2008 through
2011, conducting multivariate time-to-event analyses (Cox models) that took the
matching design into account to evaluate time from inclusion until performance of
the given number of each of six recommended examinations/tests. RESULTS: GPs
belonging to a diabetes-care network adhered more closely to clinical practice
guidelines but our result were slightly pronounced. Hazard ratios (HR) were
significantly higher for patients of network GPs for the implementation of 3
HbA1C assays (HRa=1.13; [95%CI=1.10-1.16]), or 1 microalbuminuria assay (1.4
[1.35-1.45]); they were lower for LDL-cholesterol assays (1.04 [1.01-1.07]) and
ophthalmological checkups (1.07 [1.04-1.10]), and not significant for creatinemia
or cardiac monitoring. CONCLUSIONS: Network GPs had better diabetes monitoring
practices for all their patients with diabetes than the other GPs, especially for
the most diabetes-specific tests. Further research is needed in other settings to
confirm the existence of this halo effect.
PMID- 27483998
TI - A combined NMR and molecular dynamics simulation study to determine the
conformational properties of rat/mouse 35-55 myelin oligodendrocyte glycoprotein
epitope implicated in the induction of experimental autoimmune encephalomyelitis.
PMID- 27483999
TI - Capparis Spinosa L. promotes anti-inflammatory response in vitro through the
control of cytokine gene expression in human peripheral blood mononuclear cells.
AB - BACKGROUND: Capparis Spinosa L. is an aromatic plant growing wild in dry regions
around the Mediterranean basin. Capparis Spinosa was shown to possess several
properties such as antioxidant, antifungal, and anti-hepatotoxic actions. In this
work, we aimed to evaluate immunomodulatory properties of Capparis Spinosa leaf
extracts in vitro on human peripheral blood mononuclear cells (PBMCs) from
healthy individuals. RESULTS: Using MTT assay, we identified a range of Capparis
Spinosa doses, which were not toxic. Unexpectedly, we found out that Capparis
Spinosa aqueous fraction exhibited an increase in cell metabolic activity, even
though similar doses did not affect cell proliferation as shown by CFSE.
Interestingly, Capparis Spinosa aqueous fraction appeared to induce an overall
anti-inflammatory response through significant inhibition of IL-17 and induction
of IL-4 gene expression when PBMCs were treated with the non toxic doses of 100
and/or 500 MUg/ml. Phytoscreening analysis of the used Capparis Spinosa
preparations showed that these contain tannins; sterols, alkaloids; polyphenols
and flavonoids. Surprisingly, quantification assays showed that our Capparis
Spinosa preparation contains low amounts of polyphenols relative to Capparis
Spinosa used in other studies. This Capparis Spinosa also appeared to act as a
weaker scavenging free radical agent as evidenced by DPPH radical scavenging
test. Finally, polyphenolic compounds including catechin, caffeic acid, syringic
acid, rutin and ferulic acid were identified by HPLC, in the Capparis spinosa
preparation. CONCLUSION: Altogether, these findings suggest that our Capparis
Spinosa preparation contains interesting compounds, which could be used to
suppress IL-17 and to enhance IL-4 gene expression in certain inflammatory
situations. Other studies are underway in order to identify the compound(s)
underlying this effect.
PMID- 27484000
TI - The mid-term outcome of primary open valvotomy for critical aortic stenosis in
early infancy - a retrospective single center study over 18 years.
AB - BACKGROUND: The objective of this study was to examine early and long-term
results of surgical aortic valvotomy in neonates and infants aged less than four
months and to identify predictors of outcome. METHODS: Between August 1994 and
April 2012, 83 consecutive patients younger than 4 months of age underwent open
heart valvotomy for critical aortic stenosis in our institution. Median age was
17 days (range 0-111 days). We examined clinical records to establish
determinants of outcome and illustrate long-term results. RESULTS: Fifty-six
patients (67 %) were neonates. Associated cardiac malformations were found in 24
patients (29 %), including multilevel left heart obstruction in 5. The median
follow-up was 4.2 years. The time-related survival rate was 87 and 85 % at 5 and
15 years, respectively. The time-related survival without reintervention was
respectively 51, 35 and 18 % at 5, 10 and 15 years. The time-related survival
without aortic valve replacement was respectively 67, 54 and 39 % at 5, 10 and 15
years. Ventricular dysfunction (p = 0.04), delayed sternal closure (p = 0.007),
endocardial fibroelastosis (p = 0.02) and low z-score of the aortic annulus (p =
0.04) were found predictors of global mortality. Ventricular dysfunction (p =
0.01) and endocardial fibroelastosis (p = 0.04) were found predictors of
reintervention. CONCLUSIONS: The experience, in our center, on the management of
critical aortic stenosis, shows a low early and late mortality, but the aortic
valvotomy is a palliative procedure and we see unfortunately a high rate of
reintervention among which the aortic valve replacement. These results suggest to
reconsider the use of aortic balloon valvotomy, and particularly for the neonates
with a low cardiac output in order to avoid the myocardial stress and the
neurological injury due to the cardiopulmonary bypass.
PMID- 27484001
TI - Exercise strategies to protect against the impact of short-term reduced physical
activity on muscle function and markers of health in older men: study protocol
for a randomised controlled trial.
AB - BACKGROUND: Muscles get smaller and weaker as we age and become more vulnerable
to atrophy when physical activity is reduced or removed. This research is
designed to investigate the potentially protective effects of two separate
exercise strategies against loss in skeletal muscle function and size, and other
key indices of health, following 14 days of reduced physical activity in older
men. METHODS: Three groups of 10 older men (aged 65-80 years) will undertake 2
weeks of reduced activity by decreasing daily steps from more than 3500 to less
than 1500 (using pedometers to record step count). Two of the three groups will
then undertake additional exercise interventions, either: 4 weeks of progressive
resistance training prior to the step-reduction intervention (PT-group), or home
based 'exercise snacking' three times per day during the step-reduction
intervention (ES-group). The third group undertaking only the step-reduction
intervention (control) will provide a comparison against which to assess the
effectiveness of the protective exercise strategies. Pre and post step-reduction
assessments of muscle function, standing balance, anthropometry and muscle
architecture will be taken. Pre and post step-reduction in postprandial metabolic
control, resting systemic inflammation, adipose inflammation, oxidative stress,
immune function, sleep quality, dietary habits, and quality of life will be
measured. The stress response to exercise, and signalling protein and gene
expression for muscle protein synthesis and breakdown following an acute bout of
exercise will also be assessed pre and post step-reduction. Rates of muscle
protein synthesis and adipose triglyceride turnover during the step-reduction
intervention will be measured using stable isotope methodology. All participants
will then undertake 2 weeks of supervised resistance training with the aim of
regaining any deficit from baseline in muscle function and size. DISCUSSION: This
study aims to identify exercise strategies that could be implemented to protect
against loss of muscle power during 2 weeks of reduced activity in older men, and
to improve understanding of the way in which a short-term reduction in physical
activity impacts upon muscle function and health. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT02495727 (Initial registration: 25 June 2015).
PMID- 27484002
TI - An exploration of men's experiences of undergoing active surveillance for
favourable-risk prostate cancer: A mixed methods study protocol.
AB - BACKGROUND: Prostate cancer is one of the most common male cancers worldwide.
Active Surveillance (AS) has been developed to allow men with lower risk disease
to postpone or avoid the adverse side effects associated with curative treatments
until the disease progresses. Despite the medical benefits of AS, it is reported
that living with untreated cancer can create a significant emotional burden for
patients. METHODS/DESIGN: The aim of this study is to gain insight into the
experiences of men eligible to undergo AS for favourable-risk PCa. This study has
a mixed-methods sequential explanatory design consisting of two phases:
quantitative followed by qualitative. Phase 1 has a multiple point, prospective,
longitudinal exploratory design. Ninety men diagnosed with favourable-risk
prostate cancer will be assessed immediately post-diagnosis (baseline) and
followed over a period of 12 months, in intervals of 3 month. Ninety age-matched
men with no cancer diagnosis will also be recruited using peer nomination and
followed up in the same 3 month intervals. Following completion of Phase 1, 10-15
AS participants who have reported both the best and worst psychological
functioning will be invited to participate in semi-structured qualitative
interviews. Phase 2 will facilitate further exploration of the quantitative
results and obtain a richer understanding of participants' personal
interpretations of their illness and psychological wellbeing. DISCUSSION: To our
knowledge, this is the first study to utilise early baseline measures; include a
healthy comparison group; calculate sample size through power calculations; and
use a mixed methods approach to gain a deeper more holistic insight into the
experiences of men diagnosed with favourable-risk prostate cancer.
PMID- 27484003
TI - Expression Profiling of Activin type IIB Receptor During Ontogeny in Broiler and
Indigenous Chicken.
AB - Augmenting the meat production is among the primary breeding objective of genetic
selection programs in poultry production. However, the knowledge about the
expression of genes regulating muscle growth at the molecular level is
inadequate. Activin type IIB receptor (ACTRIIB) has been reported to play vital
role in the negative regulation of muscle growth by binding to multiple members
of transforming growth factor-beta superfamily. The present investigation was
carried out to comprehend the trend of ACTRIIB messenger RNA in pectoralis major
muscle during embryonic (E5-20) and post embryonic age (days 1, 14, 28, and 42)
in both Control Broiler (CB) and Aseel by using Real-time PCR. The expression
profile of ACTRIIB gene displayed a similar trend in CB and Aseel, however Aseel
showed significantly (P < 0.001) higher transcription throughout the period. The
fold change in expression of ACTRIIB in Aseel relative to CB varied from 3.94 to
14.72 folds and 3.28 to 7.14 folds during embryonic and post embryonic age,
respectively. ACTRIIB exhibited its peak on E7, E11, and E16 during embryonic
age, which coincides with the formation of primary and secondary muscle fibers in
both lines. While at the time of post-embryonic age, ACTRIIB showed highest
transcription on day 1 and lowest transcription on day 28 in both CB and Aseel.
Within each line, the expression of ACTRIIB differed significantly (P < 0.001)
between days in the course of embryonic and post-embryonic period. ACTRIIB gene
expression had significant (P < 0.05) effect on all carcass traits except neck
weight. Our results suggest that Aseel expressed higher levels of ACTRIIB
transcript than CB. The study inferred that expression pattern of ACTRIIB was
analogous in both CB and Aseel, which might imply that molecular mechanisms
underlying muscle development and regulation are comparable in nature.
PMID- 27484005
TI - A cross-sectional, facility based study of comorbid non-communicable diseases
among adults living with HIV infection in Zimbabwe.
AB - BACKGROUND: Increased antiretroviral therapy uptake in sub-Saharan Africa has
resulted in improved survival of the infected. Opportunistic infections are
declining as leading causes of morbidity and mortality. Though comprehensive data
are lacking, concern has been raised about the rapid emergence of non
communicable diseases (NCDs) in the African HIV care setting. We therefore set
out to characterise the NCD/HIV burden among adults living and ageing with HIV
infection in Zimbabwe. METHODS: We conducted a cross-sectional study among
patients receiving care in a public sector facility. We reviewed patient records
and determined the prevalence of comorbid and multi-morbid NCDs. Associations
with patient characteristics were evaluated using univariate and multi-variate
logistic regression modelling. Significance testing was done using 2-sided p
values and 95 % confidence intervals calculated. RESULTS: We recruited 1033
participants. 31 % were men. Significant gender differences included: older
median age, more advanced disease at baseline, and greater use of stavudine and
protease inhibitor containing regimens in men compared to women. The prevalence
of comorbidity and multi-morbidity were, respectively, 15.3 % (95 % CI 13.3-17.7
%) and 4.5 % (95 % CI 3.4-6.0 %). Women had higher rates than men of both co
morbidity and multi-morbid ity: 21.8 vs. 14.9 %; p = 0.010 and 5.3 vs. 2.9 %; p =
0.025 respectively. The commonly observed individual NCDs were hypertension [10.2
%; (95 % CI 8.4-12.2 %)], asthma [4.3 % (95 % CI 3.1-5.8 %)], type 2 diabetes
mellitus [2.1 % (95 % CI 1.3-3.2 %)], cancer [1.8 % (95 % CI 1.1-2.8 %)], and
congestive cardiac failure [1.5 % (95 % CI 0.9-2.5 %)]. After adjusting for
confounding, only age categories 45-<=55 years (AOR 2.25; 95 % CI 1.37-3.69) and
>55 years (AOR 5.42; 95 % CI 3.17-9.26), and female gender (AOR 2.12; 95 % CI
1.45-3.11) remained significantly and strongly associated with comorbidity risk.
CONCLUSIONS: We found a substantial burden of comorbid non-communicable diseases
among HIV infected patients in a high HIV and low-income setting. Integrating non
communicable diseases care, including active screening, with HIV care is
recommended.
PMID- 27484007
TI - Corrigendum.
PMID- 27484006
TI - A meta-analysis of long follow-up outcomes of laparoscopic Nissen (total) versus
Toupet (270 degrees ) fundoplication for gastro-esophageal reflux disease based
on randomized controlled trials in adults.
AB - BACKGROUND: Laparoscopic Nissen fundoplication (LNF) is the most common surgical
procedure for the surgical management of gastro-esophageal reflux disease (GERD).
Laparoscopic Toupet fundoplication (LTF) has been reported to have a lower
prevalence of postoperative complications yet still obtain a similar level of
reflux control. We conducted a meta-analysis to confirm the value of LNF and LTF.
METHODS: PubMed, Medline, Embase, Cochrane Library and Springerlink were searched
for randomized controlled trials (RCTs) comparing LNF and LTF. Data regarding the
benefits and adverse results of two techniques were extracted and compared using
a meta-analysis. RESULTS: Eight eligible RCTs comparing LNF (n = 625) and LTF (n
= 567) were identified. There were no significant differences between LNF and LTF
with regard to hospitalization duration, perioperative complications, patient
satisfaction, postoperative heartburn, regurgitation, postoperative DeMeester
scores, or esophagites. A shorter operative time and higher postoperative lower
esophageal sphincter pressure were associated with LNF. Prevalence of
postoperative dysphagia, gas-bloating, inability to belch, dilatation for
dysphagia and reoperation were higher after LNF, but subgroup analyses showed
that differences with respect to dysphagia between LNF and LTF disappeared over
time. Subgroup analyses did not support "tailored therapy" according to
preoperative esophageal motility. CONCLUSIONS: LNF and LTF have equivalently good
control of GERD and result in a similar prevalence of patient satisfaction. Based
on current evidence, it is not rational or advisable to abandon LNF when choosing
a surgical procedure for GERD.
PMID- 27484008
TI - Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper
Tract Urothelial Carcinomas and other Kidney Carcinomas.
AB - Collecting duct carcinoma (CDC) is a kidney cancer subtype that is thought to
arise from principal cells in distal parts of the collecting ducts. Some studies
suggested an overlap of CDC with upper tract urothelial carcinoma (UTUC), making
the pathological diagnosis challenging. Herein, we performed for the first time
transcriptome sequencing of CDC and compared them to UTUC and renal cell
carcinoma subtypes. We discovered that CDC displays a unique transcriptomic
signature among kidney cancer subtypes, with a putative cell of origin in the
distal convoluted tubules. Hierarchical unsupervised clustering reveals that the
CDC signature is closer to that of other RCC subtypes than to UTUC, which is
similar to that of bladder carcinoma. CDC is characterized by a metabolic shift,
with impairment of oxidoreductase activity, pyruvate metabolism and the
tricarboxlyic acid cycle, as well as an immunogenic response consistent with
increased tumor infiltrating lymphocytes, particularly within metastatic cases.
In addition, pathways differentially altered between CDC and UTUC point to a
basal-like phenotype of CDC in contrast to the luminal-like signature of UTUC. We
conclude that CDC harbors a pathognomonic transcriptomic signature characterized
by immunogenic and a metabolic aberrations, indicating that targeting these
processes might provide therapeutic options for patients.
PMID- 27484009
TI - Explaining large mortality differences between adjacent counties: a cross
sectional study.
AB - BACKGROUND: Extensive geographic variation in adverse health outcomes exists, but
global measures ignore differences between adjacent geographic areas, which often
have very different mortality rates. We describe a novel application of advanced
spatial analysis to 1) examine the extent of differences in mortality rates
between adjacent counties, 2) describe differences in risk factors between
adjacent counties, and 3) determine if differences in risk factors account for
the differences in mortality rates between adjacent counties. METHODS: We
conducted a cross-sectional study in Missouri, USA with 2005-2009 age-adjusted
all-cause mortality rate as the outcome and county-level explanatory variables
from a 2007 population-based survey. We used a multi-level Gaussian model and a
full Bayesian approach to analyze the difference in risk factors relative to the
difference in mortality rates between adjacent counties. RESULTS: The average
mean difference in the age-adjusted mortality rate between any two adjacent
counties was -3.27 (standard deviation = 95.5) per 100,000 population (maximum =
258.80). Six variables were associated with mortality differences: inability to
obtain medical care because of cost (beta = 2.6), hospital discharge rate (beta =
1.03), prevalence of fair/poor health (beta = 2.93), and hypertension (beta =
4.75) and poverty prevalence (beta = 6.08). CONCLUSIONS: Examining differences in
mortality rates and associated risk factors between adjacent counties provides
additional insight for future interventions to reduce geographic disparities.
PMID- 27484010
TI - OPRM1 genotype interacts with serotonin system dysfunction to predict alcohol
heightened aggression in primates.
AB - Although the notion that alcohol promotes violence is widespread, not all
individuals are aggressive while intoxicated. Genetic variation could be a
contributing factor to individual differences in alcohol-heightened aggression.
The present study examines the effects of OPRM1C77G genotype on responses to
threat in rhesus macaques under normal conditions and following alcohol
administration. Prior studies have shown that a low CSF level of 5-HIAA is a
trait marker for individuals prone to escalated aggression. We wanted to examine
whether the predictive value for this marker on aggression was moderated by OPRM1
genotype. Animals were administered alcohol (BAC 100-200 mg%), were provoked by a
human intruder, and aggressive responses were recorded. Factor analysis was
performed to generate aggressive response factors, which were then used as
dependent variables for ANOVA, with OPRM1 genotype and CSF 5-HIAA as independent
variables. Factor analysis generated three factors ('Threatening', 'Distance
Decreasing' and 'High Intensity'). We found that High Intensity aggression was
increased among carriers of the OPRM1 G allele, especially among individuals with
low CSF levels of 5-HIAA. Aggression in the non-intoxicated state was predicted
by 5-HIAA, but not by genotype. This study demonstrates that OPRM1 genotype
predicts alcohol-heightened aggression in rhesus macaques with low CSF levels of
5-HIAA. Because OPRM1 variation predicts similar effects on alcohol response and
behavior in humans and macaques, this study could suggest a role for OPRM1
genotype in alcohol-heightened aggression in humans. If so, it may be that
compounds that block this receptor could reduce alcohol-associated violence in
selected patient populations.
PMID- 27484011
TI - Chemistry, manufacturing and control (CMC) and clinical trial technical support
for influenza vaccine manufacturers.
AB - With the support of the Biomedical Advanced Research and Development Authority
(BARDA) of the US Department of Health and Human Services, PATH has contributed
to the World Health Organization's (WHO's) Global Action Plan for Influenza
Vaccines (GAP) by providing technical and clinical assistance to several
developing country vaccine manufacturers (DCVMs). GAP builds regionally based
independent and sustainable influenza vaccine production capacity to mitigate the
overall global shortage of influenza vaccines. The program also ensures adequate
influenza vaccine manufacturing capacity in the event of an influenza pandemic.
Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of
Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH
also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil;
Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology
Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing
influenza vaccine manufacturing capability and required technical support from
PATH to improve vaccine yield, process efficiency, and product formulation. PATH
has provided customized technical support for the manufacturing process to each
DCVM based on their respective requirements. Additionally, PATH, working with
BARDA and WHO, supported several DCVMs in the clinical development of influenza
vaccine candidates progressing toward national licensure or WHO prequalification.
As a result of the activities outlined in this review, several companies were
able to make excellent progress in developing state-of-the-art manufacturing
processes and completing early phase clinical trials. Licensure trials are
currently ongoing or planned for several DCVMs.
PMID- 27484012
TI - Influence of adenovirus and MVA vaccines on the breadth and hierarchy of T cell
responses.
AB - Viral-vectored vaccines are in clinical development for several infectious
diseases where T-cell responses can mediate protection, and responses to sub
dominant epitopes is needed. Little is known about the influence of MVA or
adenoviral vectors on the hierarchy of the dominant and sub-dominant T-cell
epitopes. We investigated this aspect in mice using a malaria immunogen. Our
results demonstrate that the T-cell hierarchy is influenced by the timing of
analysis, rather than by the vector after a single immunization, with hierarchy
changing over time. Repeated homologous immunization reduced the breadth of
responses, while heterologous prime-boost induced the strongest response to the
dominant epitope, albeit with only modest response to the sub-dominant epitopes.
PMID- 27484014
TI - Radiotherapy for breast cancer: The predictable consequences of an unmet need.
AB - Radiotherapy has had a transformative impact on the treatment of breast cancer,
but is unavailable to the majority of breast cancer patients in low- and middle
income countries. In these settings, where many women present with advanced
disease at an age when they are often the primary caregiver for their families,
the lack of access to radiotherapy is particularly devastating. Until recently,
this disparity has been largely neglected in the medical literature and it had
been difficult to convince governments, industry, and policymakers of the
importance of investing in radiotherapy, as well as broader cancer control
strategies, in low-resource settings. The Lancet Radiotherapy Commission report
published in 2015 challenged many assumptions about the affordability of
radiotherapy treatment. Data from the Commission is presented here to support
radiotherapy investment for breast cancer and discuss how the morbidity and
premature mortality among adult women caused by breast cancer has a huge
detrimental effect on both the health sector and the economy.
PMID- 27484013
TI - Effect of 4 % chlorhexidine on cord colonization among hospital and community
births in India: a randomized controlled study.
AB - BACKGROUND: Infections are the single most important cause of neonatal mortality
in developing countries. Results from trials in Asia evaluating the effect of
chlorhexidine on neonatal mortality have been encouraging but limited data are
available on the impact of cord cleansing on bacterial colonization. Further, no
data from facility deliveries and impact with time is available. This pilot study
was aimed to evaluate the impact of 4 % commercially prepared chlorhexidine on
cord colonization and density of colonization among newborns in India. METHODS:
Three hundred twenty-six newborns (hospital-247; community-79) were enrolled
within 24 h of birth and randomly assigned to one of three groups: chlorhexidine,
placebo or dry cord care. Umbilical swabs were collected at baseline, 2- and 48-
hours after intervention application. RESULTS: At baseline, growth positivity
(any bacterial growth) was 20 % (50 of 247 swabs) and 81 % (64 of 79 swabs) among
hospital and community born neonates, respectively. In both settings,
chlorhexidine compared to placebo and dry cord care, reduced colonization
following 2- and 48-hour post application. Chlorhexidine significantly reduced 48
hour post application colony counts in comparison to placebo [Hospital: mean
difference = -1.01; 95 % CI: -1.72, -0.30 Community: mean difference = -1.76; 95
% CI: -2.60, -0.93] and dry cord care [Hospital: mean difference = -1.16; 95 %
CI: -1.93, -0.39 Community: mean difference = -2.23; 95 % CI: -3.18, -1.29].
Differences were similar for gram-positive and gram-negative bacteria.
CONCLUSIONS: Cord cleansing with 4 % chlorhexidine soon after birth reduced
colonization as well as density of colonization significantly; however this pilot
study does not address the impact of chlorhexidine on mortality. The control
preparation neither increased or decreased colonization. TRIAL REGISTRATION:
CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01528852, Registered February
7, 2012.
PMID- 27484015
TI - Perspectives from a weary surgical oncologist in Sub-Saharan Africa.
AB - This is an personal reflection on the challenges of managing advanced breast
cancer in a resource-poor setting, focussing on financial constraints,
unavailability of treatment options, and the personal cost to patient and
surgeon.
PMID- 27484016
TI - Effects of a regional guideline for completion axillary lymph node dissection in
women with breast cancer to reduce variation in surgical practice: A qualitative
study of physicians' views.
AB - BACKGROUND: Recently the impact of completion axillary lymph node dissection
(cALND) after positive sentinel lymph node biopsy on significant outcomes has
been questioned, leading to variation in surgical practice. To address this
variation, a multidisciplinary working group created a regional guideline for
cALND. We explored the views and experiences of surgeons, medical oncologists
(MOs), radiation oncologists (ROs) in a qualitative study that examined guideline
implementation in practice. METHODS: The Pathman framework (awareness, agreement,
adoption and adherence) informed the interview guide design and analysis. Semi
structured interviews were conducted with MOs, ROs and surgeons and transcribed.
Transcripts were coded independently by 2 members of the study team and analyzed.
Disagreements were resolved through consensus. RESULTS: Twenty-eight physicians
(5 MO; 6RO; 17S) of 41 (68% of those approached) were interviewed. Ten of 11
(91%) hospital sites (54% community; 46% academic) and all 4 cancer clinics
within the region were represented. Twenty-seven physicians (96%) were aware of
the guideline, with all physicians reporting agreement and general adherence to
the guideline. Most physicians indicated nodal factors, age and patient
preference were key components of cALND decision-making. Physicians from all
disciplines perceived that the guideline helped reduce variation in practice
across the region. There were concerns that the guideline could be applied
rigidly and not permit individual decision-making. CONCLUSIONS: Physicians
identified breast cancer as an increasingly complex and multidisciplinary issue.
Facilitators to guideline implementation included perceived flexibility and buy
in from all disciplines, while individual patient factors and controversial
supporting evidence may hinder its implementation.
PMID- 27484017
TI - Similar biological activity in skin prick test for Oralair(r) (8200 BAU) and
Grazax(r) (6200 BAU) reinforces effective SLIT dosing level.
AB - In Europe, allergen extracts are standardized based on skin prick wheal size in
20-30 allergic subjects. To understand the biological activity of clinically
effective Sublingual immunotherapy, we used this method to determine the
biological activity of solution and tablet Timothy grass pollen (TIM) extracts,
compared to an FDA-approved extract (Reference) of 10 000 BAU/ml. Blinded,
quadruplicate skin prick tests with concentrate and three serial half-log
dilutions allowed the construction of a semilogarithmic regression line per
extract. Bioequivalent allergy units (BAU) values were obtained from the
comparison with reference. Extracts and dilutions showed a neat linear dose
response (all: R2 > 0.98) in 33 rhinitis patients. Relative potencies:
Staloral(r) 12 000 BAU/ml, Soluprick(r) 10 300 BAU/ml, Oralair(r) 8200 BAU, and
Grazax(r) 6200 BAU. Even though all extract concentrates differed in wheal size
(P = 0.01-0.001), Grazax(r) producing a 25% smaller wheal size than Oralair(r) ,
and the biological activity of these clinically effective TIM tablets led in the
same range (6200-8200 BAU; 0.92-1.23 cm2 ). SLIT dose-finding studies for other
pollens might start with allergen extracts producing 1.1 cm2 wheal surface.
PMID- 27484018
TI - Impact of an evidence-based guideline on the management of community-acquired
bacterial meningitis: a prospective cohort study.
AB - OBJECTIVES: To study the impact of an evidence-based guideline on the management
of community-acquired bacterial meningitis. METHODS: We performed an interrupted
time series analysis in a prospective nationwide cohort study from 2006 to 2015.
The guideline stresses the importance of cranial imaging before lumbar puncture
(LP) in selected patients based on clinical criteria, and early treatment with
amoxicillin and a third-generation cephalosporin for adults with suspected
community-acquired bacterial meningitis. The guideline was published in April
2013. RESULTS: We included 1326 episodes before and 210 episodes after guideline
introduction. Cranial imaging was performed before LP in 497 (84%) of 591
episodes with clinical criteria warranting computed tomography (CT). The
guideline did not improve this (increase of 2%; 95% confidence interval (CI), -15
to 19). Without these criteria, imaging before LP occurred in 606 (67%) of 900
episodes, also without effect of the guideline (increase of 1%; 95% CI, -25 to
28). The estimate of effect of the guideline for treatment with the recommended
antibiotic regimen was an increase of 19.5% (95% CI, 13.5 to 25.5), and there was
a trend towards more frequent initiation of treatment before CT. There was no
association between delay in antibiotic treatment due to imaging before LP and
unfavourable outcome (odds ratio, 1.14; 95% CI 0.86 to 1.52). CONCLUSIONS:
Cranial imaging is performed before LP in the majority of patients with bacterial
meningitis, irrespective of guideline indications. The guideline introduction was
associated with a trend towards early initiation of treatment before imaging and
with increased adherence to antibiotic policy.
PMID- 27484019
TI - Corrigendum to 'Response to Letter to the Editor "Alcohol hand rub consumption
objectives in European hospitals need to be revisited"' [Clin Microbiol Infect
(2016) 578].
PMID- 27484020
TI - Discontinuation of echinocandin and azole treatments led to the disappearance of
an FKS alteration but not azole resistance during clonal Candida glabrata
persistent candidaemia.
AB - To give an indication of a fitness cost conferred by FKS mutation-associated
echinocandin resistance in Candida glabrata during human infection. Six C.
glabrata clinical strains sequentially isolated from blood and a hepatic abscess
in a solid organ transplant recipient were analysed. The patient had received
long-term azole and echinocandin therapy for invasive aspergillosis and
persistent candidaemia. Minimal inhibitory concentrations were determined by the
European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth
microdilution method. Molecular mechanisms of antifungal resistance were
determined by sequencing hot spots of the FKS. Strain relatedness was determined
using a microsatellite-based typing method. Typing analysis revealed an identical
microsatellite pattern for all isolates, supporting a close relation. The first
C. glabrata isolate showed wild-type phenotype (i.e. susceptibility to
echinocandins and low level of azole resistance). After voriconazole therapy, the
C. glabrata quickly acquired pan-azole resistance. Later, echinocandin treatment
led to the emergence of a FKS2 S663P alteration and echinocandin resistance.
After disruption of both azole and echinocandin therapy in favour of liposomal
amphotericin B, C. glabrata isolates regained full susceptibility to echinocandin
and lost the FKS2 S663P alteration while nonetheless maintaining their pan-azole
resistance. Our clinical report supports the potential existence of a fitness
cost conferred by FKS mutation in C. glabrata, as disruption of treatment led to
a rapid disappearance of the resistant clone. This suggests that a more
restricted use and/or a discontinuous administration of echinocandins may limit
the spread of clinical resistance to this class.
PMID- 27484022
TI - Abstracts of the 50th Workshop for Pediatric Research.
PMID- 27484021
TI - Reduced nocturnal hypoglycaemia with basal insulin peglispro compared with
insulin glargine: pooled analyses of five randomized controlled trials.
AB - Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential
action, resulting from reduced peripheral effects. This report summarizes
hypoglycaemia data from five BIL phase III studies with insulin glargine as the
comparator, including three double-blind trials. Prespecified pooled analyses (n
= 4927) included: patients with type 2 diabetes (T2D) receiving basal insulin
only, those with T2D on basal-bolus therapy, and those with type 1 diabetes
(T1D). BIL treatment resulted in a 36-45% lower nocturnal hypoglycaemia rate
compared with glargine, despite greater reduction in glycated haemoglobin (HbA1c)
and higher basal insulin dosing. The total hypoglycaemia rate was similar in
patients with T2D on basal treatment only, trended towards being higher (10%) in
patients with T2D on basal-bolus treatment (p = .053), and was 15% higher (p <
.001) with BIL versus glargine in patients with T1D, with more daytime
hypoglycaemia in the T1D and T2D groups who were receiving basal-bolus therapy.
In T1D, during the maintenance treatment period (26-52 weeks), the total
hypoglycaemia rate was not significantly different. There were no differences in
severe hypoglycaemia in the T1D or T2D pooled analyses. BIL versus glargine
treatment resulted in greater HbA1c reduction with less nocturnal hypoglycaemia
in all patient populations, higher daytime hypoglycaemia with basal-bolus therapy
in the T1D and T2D groups, and an associated increase in total hypoglycaemia in
the patients with T1D.
PMID- 27484023
TI - Acceptability and feasibility of point-of-care CD4 testing on HIV continuum of
care in low and middle income countries: a systematic review.
AB - BACKGROUND: CD4 testing is, and will remain an important part of HIV treatment
and care in low and middle income countries (LMICs). We report the findings of a
systematic review assessing acceptability and feasibility of POC CD4 testing in
field settings. METHODS: Electronic databases were searched for studies published
in English between 2005 and 2015 that describe POC CD4 platforms. Studies
conducted in LMICs and under field conditions outside a laboratory environment
were eligible. Qualitative and descriptive data analysis was used to present the
findings. RESULTS: Twelve studies were included, 11 of which were conducted in
sub-Saharan countries and used one POC CD4 test (The Alere Pima CD4). Patients
reported positively regarding the implementation of POC CD4 testing at primary
health care and community level with >=90 % of patients accepting the test across
various study settings. Health service providers expressed preference toward POC
CD4 testing as it is easy-to-use, efficient and satisfied patients' needs to a
greater extent as compared to conventional methods. However, operational
challenges including preference toward venous blood rather than finger-prick
sampling, frequent device failures and operator errors, quality of training for
test operators and supervisors, and increased staff workload were also
identified. CONCLUSIONS: POC CD4 testing seems acceptable and feasible in LIMCs
under field conditions. Further studies using different POC CD4 tests available
on the market are required to provide critical data to support countries in
selection and implementation of appropriate POC CD4 technologies.
PMID- 27484025
TI - [Co-existence of cardiovascular risk factors in patients with diabetes and
peripheral vascular disease].
PMID- 27484024
TI - The dehydroalanine effect in the fragmentation of ions derived from polypeptides.
AB - The fragmentation of peptides and proteins upon collision-induced dissociation
(CID) is highly dependent on sequence and ion type (e.g. protonated,
deprotonated, sodiated, odd electron, etc.). Some amino acids, for example
aspartic acid and proline, have been found to enhance certain cleavages along the
backbone. Here, we show that peptides and proteins containing dehydroalanine, a
non-proteinogenic amino acid with an unsaturated side-chain, undergo enhanced
cleavage of the N-Calpha bond of the dehydroalanine residue to generate c- and z
ions. Because these fragment ion types are not commonly observed upon activation
of positively charged even-electron species, they can be used to identify
dehydroalanine residues and localize them within the peptide or protein chain.
While dehydroalanine can be generated in solution, it can also be generated in
the gas phase upon CID of various species. Oxidized S-alkyl cysteine residues
generate dehydroalanine upon activation via highly efficient loss of the alkyl
sulfenic acid. Asymmetric cleavage of disulfide bonds upon collisional activation
of systems with limited proton mobility also generates dehydroalanine.
Furthermore, we show that gas-phase ion/ion reactions can be used to facilitate
the generation of dehydroalanine residues via, for example, oxidation of S-alkyl
cysteine residues and conversion of multiply-protonated peptides to radical
cations. In the latter case, loss of radical side-chains to generate
dehydroalanine from some amino acids gives rise to the possibility for residue
specific backbone cleavage of polypeptide ions. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27484026
TI - Reference Values of Total Lean Mass, Appendicular Lean Mass, and Fat Mass
Measured with Dual-Energy X-ray Absorptiometry in a Healthy Mexican Population.
AB - The aim of this study was to develop age- and gender-specific reference values of
total lean body mass (LBM), appendicular lean body mass (ALBM), and fat mass (FM)
by dual-energy X-ray absorptiometry (DXA) data in a healthy Mexican population. A
cross-sectional analysis was conducted on 9518 healthy subjects 7-89 years of age
participating in the baseline measurement of the Health Workers Cohort Study.
Using DXA, LBM, ALBM, and FM were measured. Using these data, LBM index (LBMI),
ALBM index (ALBMI), and fat mass index (FMI) were calculated. LMI, ALMI, and FMI
were calculated as the LBM, ALBM, and FM kg divided by the height in meters
squared. Males and females were analyzed separately; sex-specific means and
standard deviations for LBM, ALBM, FM, LBMI, ALBMI, and FMI were calculated. A
total of 2829 males and 6694 females were included in the final analysis. Strong
sex gaps were observed after 12 years in LBM, ALBM, LBMI, and ALBMI (P < 0.01).
LBM and ALBM values continue to increase for males up to age 20; females
plateaued approximately after age 15. Significant sex differences were also
observed for FM and FMI. Significant sex- and age-related differences exist in
LBM, ALBM, and FM in the Mexican population. In addition, given the null data
available in this area, these reference values may be useful in the evaluation of
a variety of childhood and adult abnormalities involving lean body mass deficits,
mainly in the assessment of muscle wasting, with important medical and
epidemiological uses.
PMID- 27484027
TI - Associations Between Body Composition and Bone Health in Children and
Adolescents: A Systematic Review.
AB - More clarification on the associations between children's and adolescents' lean
and fat mass (LM and FM) on the one hand and their bone health on the other hand
is needed, given the rising prevalence of overweight and obesity in this
population. This systematic literature review aimed to describe the current
evidence on these associations. Data sources were Medline/PubMed, EMBASE, CINAHL
and The Cochrane Library (up to November 2014). Search items included LM, FM,
children and adolescents (0-18 years), bone health measured with dual-energy X
ray absorptiometry and peripheral quantitative computed tomography (pQCT) and
search items concerning study design: observational and longitudinal studies. The
study populations were healthy children and adolescents including obese children.
Children with other diseases and clinical series of study subjects were excluded.
Based on the studies included in this review (n = 19), there is a consensus that
the contribution of LM to the variance of the different bone parameters is larger
than the contribution of FM and that an increase in LM is associated with an
increase in bone parameters. Most of the studies indicated that the increase in
bone parameters seen in overweight and obese children and adolescents is due to
an increase in LM and not to greater FM. The results on the association between
body fat and bone parameters were contradictory and depended on children's age
and sex. Still more data from studies with a longitudinal study design using
(high resolution) pQCT and a representative sample are needed to get further
insight in the associations between body fat and bone parameters in children,
specifically concerning differences in sex, skeletal site and fat depots.
PMID- 27484029
TI - Down to the Molecular Mechanisms of Host-Pathogen Interactions.
PMID- 27484028
TI - Decompensated liver cirrhosis and neural regulation of mesenteric vascular tone
in rats: role of sympathetic, nitrergic and sensory innervations.
AB - We evaluated the possible alterations produced by liver cholestasis (LC), a model
of decompensated liver cirrhosis in sympathetic, sensory and nitrergic nerve
function in rat superior mesenteric arteries (SMA). The vasoconstrictor response
to electrical field stimulation (EFS) was greater in LC animals. Alpha
adrenoceptor antagonist phentolamine and P2 purinoceptor antagonist suramin
decreased this response in LC animals more than in control animals. Both non
specific nitric oxide synthase (NOS) L-NAME and calcitonin gene related peptide
(CGRP) (8-37) increased the vasoconstrictor response to EFS more strongly in LC
than in control segments. Vasomotor responses to noradrenaline (NA) or CGRP were
greater in LC segments, while NO analogue DEA-NO induced a similar vasodilation
in both experimental groups. The release of NA was not modified, while those of
ATP, nitrite and CGRP were increased in segments from LC. Alpha 1 adrenoceptor,
Rho kinase (ROCK) 1 and 2 and total myosin phosphatase (MYPT) expressions were
not modified, while alpha 2B adrenoceptor, nNOS expression and nNOS and MYPT
phosphorylation were increased by LC. Together, these alterations might
counteract the increased splanchnic vasodilation observed in the last phases of
decompensated liver cirrhosis.
PMID- 27484030
TI - Mixed dentition space analysis among Nepalese Brahmins/Chhetris.
AB - BACKGROUND: Mixed dentition space analysis forms an important part of orthodontic
diagnosis and treatment planning. Regression equations are widely used for mixed
dentition analysis which can vary among races. This study aimed to find out the
new regression equation in estimating the size of unerupted canines and premolars
for Nepalese Brahmins/Chhetris. METHODS: Hundred Nepalese Brahmins/Chhetris (50
males and 50 females) who met our criteria were selected among the patients
attending to the Orthodontic Out-Patient Department, Institute of Medicine,
Kathmandu. The mesiodistal widths of all mandibular permanent incisors; maxillary
and mandibular canines and premolars were measured and analyzed. The results were
also compared with predicted values from the Moyers and the Tanaka and Johnston
methods. Correlation and linear regression analyses were performed between the
predicted and actual tooth sizes for Nepalese Brahmins/Chhetris and standard
regression equations were developed. RESULTS: No significant differences were
observed when the sum of canine and premolars of one quadrant is compared between
sides and sex. Significant and high positive correlations were found between the
mandibular incisors and the combined mesiodistal widths of the canines and
premolars for the maxillary (r = 0.72) and mandibular (r = 0.73) segments.
Significant differences were observed between the measured values from this study
and from Moyers (50 % and 75 % probability) and Tanaka-Johnston methods.
CONCLUSIONS: The equations and charts commonly used for North American children
(50(th) or 75(th) percentile) did not accurately predict for our sample, so new
regression equations and tables were developed for Nepalese Brahmins/Chhetris
children.
PMID- 27484031
TI - Complete human CD1a deficiency on Langerhans cells due to a rare point mutation
in the coding sequence.
PMID- 27484032
TI - Rapid molecular diagnostics of severe primary immunodeficiency determined by
using targeted next-generation sequencing.
AB - BACKGROUND: Primary immunodeficiency diseases (PIDDs) are inherited disorders of
the immune system. The most severe form, severe combined immunodeficiency (SCID),
presents with profound deficiencies of T cells, B cells, or both at birth. If not
treated promptly, affected patients usually do not live beyond infancy because of
infections. Genetic heterogeneity of SCID frequently delays the diagnosis; a
specific diagnosis is crucial for life-saving treatment and optimal management.
OBJECTIVE: We developed a next-generation sequencing (NGS)-based multigene
targeted panel for SCID and other severe PIDDs requiring rapid therapeutic
actions in a clinical laboratory setting. METHODS: The target gene capture/NGS
assay provides an average read depth of approximately 1000*. The deep coverage
facilitates simultaneous detection of single nucleotide variants and exonic copy
number variants in one comprehensive assessment. Exons with insufficient coverage
(<20* read depth) or high sequence homology (pseudogenes) are complemented by
amplicon-based sequencing with specific primers to ensure 100% coverage of all
targeted regions. RESULTS: Analysis of 20 patient samples with low T-cell
receptor excision circle numbers on newborn screening or a positive family
history or clinical suspicion of SCID or other severe PIDD identified deleterious
mutations in 14 of them. Identified pathogenic variants included both single
nucleotide variants and exonic copy number variants, such as hemizygous nonsense,
frameshift, and missense changes in IL2RG; compound heterozygous changes in ATM,
RAG1, and CIITA; homozygous changes in DCLRE1C and IL7R; and a heterozygous
nonsense mutation in CHD7. CONCLUSION: High-throughput deep sequencing analysis
with complete clinical validation greatly increases the diagnostic yield of
severe primary immunodeficiency. Establishing a molecular diagnosis enables early
immune reconstitution through prompt therapeutic intervention and guides
management for improved long-term quality of life.
PMID- 27484033
TI - Successful hematopoietic stem cell transplantation for myelofibrosis in an adult
with warts-hypogammaglobulinemia-immunodeficiency-myelokathexis syndrome.
PMID- 27484034
TI - Reply.
PMID- 27484035
TI - Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant
translocation (PVT1) as a novel regulator of the asthmatic phenotype in human
airway smooth muscle.
AB - BACKGROUND: The mechanism underlying nonsevere and severe asthma remains unclear,
although it is commonly associated with increased airway smooth muscle (ASM)
mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating
healthy primary airway smooth muscle cells (ASMCs), whereas changed expression
has been observed in CD8 T cells from patients with severe asthma. METHODS:
Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified
as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to
dexamethasone and FCS. mRNA and lncRNA expression was measured by using a
microarray and quantitative real-time PCR. Bioinformatic analysis was used to
examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant
translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small
interfering RNAs, and the effect on ASMC phenotype was examined. RESULTS: The
mRNA expression profile was significantly different between patient groups after
exposure to dexamethasone and FCS, and these were associated with biological
pathways that might be relevant to the pathogenesis of asthma, including cellular
proliferation and pathways associated with glucocorticoid activity. We also
observed a significant change in lncRNA expression, yet the expression of only
one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive
nonsevere asthma and increased in patients with corticosteroid-insensitive severe
asthma. Subsequent targeting studies demonstrated the importance of this lncRNA
in controlling both proliferation and IL-6 release in ASMCs from patients with
severe asthma. CONCLUSIONS: lncRNAs are associated with the aberrant phenotype
observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in
reducing airway remodeling in asthmatic patients.
PMID- 27484036
TI - T-cell receptor-mediated cross-reactivity to different allergens is driven by
recognition of homologous, phylogenetically conserved epitopes.
PMID- 27484037
TI - Relationships among aeroallergen sensitization, peripheral blood eosinophils, and
periostin in pediatric asthma development.
AB - BACKGROUND: Biomarkers, preferably noninvasive, that predict asthma inception in
children are lacking. OBJECTIVE: Little is known about biomarkers of type 2
inflammation in early life in relation to asthma inception. We evaluated
aeroallergen sensitization, peripheral blood eosinophils, and serum periostin as
potential biomarkers of asthma in children. METHODS: Children enrolled in the
Childhood Origins of ASThma study were followed prospectively from birth. Blood
samples were collected at ages 2, 4, 6, and 11 years, and serum-specific IgE
levels, blood eosionophil counts, and periostin levels were measured in 244
children. Relationships among these biomarkers, age, and asthma were assessed.
RESULTS: Serum periostin levels were approximately 2- to 3-fold higher in
children than previously observed adult levels. Levels were highest at 2 years
(145 ng/mL), and did not change significantly between 4 and 11 years (128 and 130
ng/mL). Age 2 year periostin level of 150 ng/mL or more predicted asthma at age 6
years (odds ratio [OR], 2.3; 95% CI, 1.3-4.4). Eosinophil count of 300 cells/MUL
or more and aeroallergen sensitization at age 2 years were each associated with
increased risk of asthma at age 6 years (OR, 3.1; 95% CI, 1.7-6.0 and OR, 3.3;
95% CI, 1.7-6.3). Children with any 2 of the biomarkers had a significantly
increased risk of developing asthma by school age (>=2 biomarkers vs none: OR,
6.6; 95% CI, 2.7-16.0). CONCLUSIONS: Serum periostin levels are significantly
higher in children than in adults, likely due to bone turnover, which impairs
clinical utility in children. Early life aeroallergen sensitization and elevated
blood eosinophils are robust predictors of asthma development. Children with
evidence of activation of multiple pathways of type 2 inflammation in early life
are at greatest risk for asthma development.
PMID- 27484038
TI - Tumor progression locus 2 reduces severe allergic airway inflammation by
inhibiting Ccl24 production in dendritic cells.
AB - BACKGROUND: The molecular and cellular pathways driving the pathogenesis of
severe asthma are poorly defined. Tumor progression locus 2 (TPL-2) (COT, MAP3K8)
kinase activates the MEK1/2-extracellular-signal regulated kinase 1/2 MAP kinase
signaling pathway following Toll-like receptor, TNFR1, and IL-1R stimulation.
OBJECTIVE: TPL-2 has been widely described as a critical regulator of
inflammation, and we sought to investigate the role of TPL-2 in house dust mite
(HDM)-mediated allergic airway inflammation. METHODS: A comparative analysis of
wild-type and Map3k8-/- mice was conducted. Mixed bone marrow chimeras,
conditional knockout mice, and adoptive transfer models were also used.
Differential cell counts were performed on the bronchoalveolar lavage fluid,
followed by histological analysis of lung sections. Flow cytometry and
quantitative PCR was used to measure type 2 cytokines. ELISA was used to assess
the production of IgE, type 2 cytokines, and Ccl24. RNA sequencing was used to
characterize dendritic cell (DC) transcripts. RESULTS: TPL-2 deficiency led to
exacerbated HDM-induced airway allergy, with increased airway and tissue
eosinophilia, lung inflammation, and IL-4, IL-5, IL-13, and IgE production.
Increased airway allergic responses in Map3k8-/- mice were not due to a cell
intrinsic role for TPL-2 in T cells, B cells, or LysM+ cells but due to a
regulatory role for TPL-2 in DCs. TPL-2 inhibited Ccl24 expression in lung DCs,
and blockade of Ccl24 prevented the exaggerated airway eosinophilia and lung
inflammation in mice given HDM-pulsed Map3k8-/- DCs. CONCLUSIONS: TPL-2 regulates
DC-derived Ccl24 production to prevent severe type 2 airway allergy in mice.
PMID- 27484039
TI - Wnt3a is critical for endothelial progenitor cell-mediated neural stem cell
proliferation and differentiation.
AB - The present study aimed to determine whether co-culture with bone marrow-derived
endothelial progenitor cells (EPCs) affects the proliferation and differentiation
of spinal cord-derived neural stem cells (NSCs), and to investigate the
underlying mechanism. The proliferation and differentiation of the NSCs were
evaluated by an MTT cell proliferation and cytotoxicity assay, and
immunofluorescence, respectively. The number of neurospheres and the number of
beta-tubulin III-positive cells were detected by microscopy. The wingless-type
MMTV integration site family, member 3a (Wnt3a)/beta-catenin signaling pathway
was analyzed by western blot analysis and reverse transcription-quantitative
polymerase chain reaction to elucidate the possible mechanisms of EPC-mediated
NSC proliferation and differentiation. The results revealed that co-culture with
EPCs significantly induced NSC proliferation and differentiation. In addition, co
culture with EPCs markedly induced the expression levels of Wnt3a and beta
catenin and inhibited the phosphorylation of glycogen synthase kinase 3beta (GSK
3beta). By contrast, Wnt3a knockdown using a short hairpin RNA plasmid in the
EPCs reduced EPC-mediated NSC proliferation and differentiation, accompanied by
inhibition of the EPC-mediated expression of beta-catenin, and its
phosphorylation and activation of GSK-3beta. Taken together, the findings of the
present study demonstrated that Wnt3a was critical for EPC-mediated NSC
proliferation and differentiation.
PMID- 27484040
TI - A sandwich-like strategy for the label-free detection of oligonucleotides by
surface plasmon fluorescence spectroscopy (SPFS).
AB - For the detection of oligonucleotides a sandwich-like detection strategy has been
developed by which the background fluorescence is significantly lowered in
comparison with surface-bound molecular beacons. Surface bound optical molecular
beacons are DNA hairpin structures comprising a stem and a loop. The end of the
stem is modified with a fluorophore and a thiol anchor for chemisorption on gold
surfaces. In the closed state the fluorophore is in close proximity to the gold
surface, and most of the fluorescence is quenched. After hybridization with a
target the hairpin opens, the fluorophore and surface become separated, and the
fluorescence drastically increases. Using this detection method the sensitivity
is limited by the difference in the fluorescence intensity in the closed and open
state. As the background fluorescence is mainly caused by non-quenched
fluorophores, a strategy to reduce the background fluorescence is to cut the
beacon in two halves. First a thiolated ssDNA capture probe strand (first half)
is chemisorbed to a gold surface together with relatively short thiol spacers.
Next the target is hybridized by one end to the surface-anchored capture probe
and by the other to a fluorophore-labeled reporter probe DNA (second half). The
signal readout is done by surface plasmon fluorescence spectroscopy (SPFS). Using
this detection strategy the background fluorescence can be significantly lowered,
and the detection limit is lowered by more than one order of magnitude. The
detection of a target takes only a few minutes and the sensor chips can be used
for multiple detection steps without a significant decrease in performance.
PMID- 27484041
TI - Transperineal sonographic findings of vulvar neurofibromatosis Type 1.
PMID- 27484042
TI - The protective role of vitamin D3 in a murine model of asthma via the suppression
of TGF-beta/Smad signaling and activation of the Nrf2/HO-1 pathway.
AB - Asthma is a common worldwide health burden, the prevalence of which is
increasing. Recently, the biologically active form of vitamin D3, 1,25
dihydroxyvitamin D3, has been reported to have a protective role in murine
asthma; however, the molecular mechanisms by which vitamin D3 attenuates asthma
associated airway injury remain elusive. In the present study, BALB/c mice were
sensitized to ovalbumin (OVA) and were administered 100 ng 1,25-dihydroxyvitamin
D3 (intraperitoneal injection) 30 min prior to each airway challenge. The
inflammatory responses were measured by ELISA, airway damage was analyzed by
hematoxylin and eosin staining, airway remodeling was analyzed by Masson staining
and periodic acid-Schiff staining, markers of oxidative stress were measured by
commercial kits, and the expression levels of alpha-smooth muscle actin (alpha
SMA) and the activity of the NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO
1) and the transforming growth factor-beta (TGF-beta)/Smad signaling pathways
were measured by immunohistochemistry and western blotting. The results
demonstrated that OVA-induced airway inflammation and immunoglobulin E
overexpression were significantly reduced by vitamin D3 treatment. In addition,
treatment with vitamin D3 decreased alpha-SMA expression, collagen deposition and
goblet cell hyperplasia, and inhibited TGF-beta/Smad signaling in the asthmatic
airway. The upregulated levels of malondialdehyde, and the reduced activities of
superoxide dismutase and glutathione in OVA-challenged mice were also markedly
restored following vitamin D3 treatment. Furthermore, treatment with vitamin D3
enhanced activation of the Nrf2/HO-1 pathway in the airways of asthmatic mice. In
conclusion, these findings suggest that vitamin D3 may protect airways from
asthmatic damage via the suppression of TGF-beta/Smad signaling and activation of
the Nrf2/HO-1 pathway; however, these protective effects were shown to be
accompanied by hypercalcemia.
PMID- 27484043
TI - Analysis of 3D strain in the human medial meniscus.
AB - This study presents a method to evaluate three-dimensional strain in meniscal
tissue using medical imaging. Strain is calculated by tracking small teflon
markers implanted within the meniscal tissue using computed tomography imaging.
The results are presented for strains in the middle and posterior third of the
medial menisci of 10 human cadaveric knees, under simulated physiologically
relevant loading. In the middle position, an average compressive strain of 3.4%
was found in the medial-lateral direction, and average tensile strains of 1.4%
and 3.5% were found in the anterior-posterior and superior-inferior directions
respectively at 5 degrees of knee flexion with an applied load of 1* body
weight. In the posterior position, under the same conditions, average compressive
strains of 2.2% and 6.3% were found in the medial-lateral and superior-inferior
directions respectively, and an average tensile strain of 3.8% was found in the
anterior-posterior direction. No statistically significant difference between
strain in the middle or posterior of the meniscus or between the global strains
is uncovered.
PMID- 27484044
TI - Reply to Comment on 'A new method to measure electron density and effective
atomic number using dual-energy CT images'.
AB - In this note, we would like to respond to the comments made by Professor Bouchard
on our recent published work and clarify some aspects of it.
PMID- 27484045
TI - Alkylamine-functionalized hexagonal boron nitride nanoplatelets as a novel
material for the reduction of friction and wear.
AB - Hexagonal boron nitride nanoplatelets (h-BNNPs), which are structurally analogous
to graphene, were prepared via the ultrasound-assisted exfoliation of h-BN powder
using N-methyl pyrrolidone as the solvent. The alkylamines with variable alkyl
chains and electron-rich nitrogen atoms were grafted onto the boron sites of the
h-BNNPs based on Lewis acid-base chemistry. The grafting of the alkylamines onto
the h-BNNPs was confirmed using FTIR, XPS, TGA and (13)C SSNMR analyses. The
crystalline and structural features of the alkylamine-functionalized h-BNNPs were
studied using XRD and HRTEM analyses. The TGA and FTIR results revealed a higher
grafting of octadecylamine (ODA) on the h-BNNPs compared to trioctylamine (TOA).
The cohesive interaction between the alkyl chains grafted onto the h-BNNPs and
the hydrocarbon chains of mineral lube base oil facilitates the dispersion of the
alkylamine-functionalized h-BNNPs. The TOA-grafted h-BNNPs (h-BNNPs-TOA)
exhibited long-term dispersion stability compared to the ODA-grafted h-BNNPs and
this was attributed to a higher degree of van der Waals interactions between the
octyl chains of the TOA molecules grafted onto the h-BNNPs and the hydrocarbon
chains of the mineral lube base oil. The tribo-performance of the h-BNNPs-TOA as
an additive to mineral lube base oil was evaluated in terms of the coefficient of
friction and wear using ball-on-disc contact geometry. A minute dosing (0.02 mg
mL(-1)) of h-BNNPs-TOA significantly improved the lubrication characteristics of
the mineral lube base oil and showed a 35 and 25% reduction of friction and wear,
respectively. The presence of boron and nitrogen on the worn scar of an aluminium
disc, as deduced from elemental mapping, confirmed the formation of a tribo
chemical thin film of h-BN lamellae on the contact interfaces, which not only
reduced the friction but also protected the contact interfaces against
undesirable wear events.
PMID- 27484046
TI - Longitudinal bone growth is impaired by direct involvement of caffeine with
chondrocyte differentiation in the growth plate.
AB - We showed previously that caffeine adversely affects longitudinal bone growth and
disrupts the histomorphometry of the growth plate during the pubertal growth
spurt. However, little attention has been paid to the direct effects of caffeine
on chondrocytes. Here, we investigated the direct effects of caffeine on
chondrocytes of the growth plate in vivo and in vitro using a rapidly growing
young rat model, and determined whether they were related to the adenosine
receptor signaling pathway. A total of 15 male rats (21 days old) were divided
randomly into three groups: a control group and two groups fed caffeine via
gavage with 120 and 180 mg kg-1 day-1 for 4 weeks. After sacrifice, the tibia
processed for the analysis of the long bone growth and proliferation of
chondrocytes using tetracycline and BrdU incorporation, respectively. Caffeine
fed animals showed decreases in matrix mineralization and proliferation rate of
growth plate chondrocytes compared with the control. To evaluate whether caffeine
directly affects chondrocyte proliferation and chondrogenic differentiation,
primary rat chondrocytes were isolated from the growth plates and cultured in
either the presence or absence of caffeine at concentrations of 0.1-1 mm,
followed by determination of the cellular proliferation or expression profiles of
cellular differentiation markers. Caffeine caused significant decreases in
extracellular matrix production, mineralization, and alkaline phosphatase
activity, accompanied with decreases in gene expression of the cartilage-specific
matrix proteins such as aggrecan, type II collagen and type X. Our results
clearly demonstrate that caffeine is capable of interfering with cartilage
induction by directly inhibiting the synthetic activity and orderly expression of
marker genes relevant to chondrocyte maturation. In addition, we found that the
adenosine type 1 receptor signaling pathway may be partly involved in the
detrimental effects of caffeine on chondrogenic differentiation, specifically
matrix production and mineralization, as evidenced by attenuation of the
inhibitory effects of caffeine by blockade of this receptor. Thus, our study
provides novel information on the integration of caffeine and adenosine receptor
signaling during chondrocyte maturation, extending our understanding of the
effect of caffeine at a cellular level on chondrocytes of the growth plate.
PMID- 27484047
TI - Victimization of Lesbian, Gay, and Bisexual People in Childhood: Associations
with Attempted Suicide.
AB - Higher rates of attempted suicide have been documented among people who identify
themselves as gay, lesbian, and bisexual (LGB) compared with heterosexuals. This
study sought to ascertain the association between childhood abuse and neglect and
attempted suicide, comparing LGBs and heterosexuals. Childhood sexual abuse among
men and childhood sexual and physical abuse among women were found to mediate the
association between LGB identity and attempted suicide. The experience of
childhood abuse likely plays a significant role in the relationship between LGB
identity and attempted suicide, but other factors such as experience of
discrimination are also important.
PMID- 27484049
TI - 1st Joint ANIRCEF-SISC Congress.
PMID- 27484048
TI - Efficacy and safety of mycophenolate mofetil in patients with active moderate-to
severe Graves' orbitopathy.
AB - CONTEXT: Graves' orbitopathy (GO) is a potentially sight-threatening disease for
which currently available medical therapy is not reliably successful.
Mycophenolate mofetil (MMF) is a selective immunosuppressant used widely in many
autoimmune diseases. Preliminary studies have shown that MMF is effective in the
treatment of active GO. OBJECTIVE: To evaluate the efficacy and safety of MMF in
patients with active moderate-to-severe GO. PATIENTS: One hundred and 74 patients
with active moderate-to-severe GO were randomized to receive either MMF or
glucocorticoids (GC). MAIN OUTCOME MEASURES: The primary outcome was overall
response at the 12th and 24th weeks; the outcome assessments included clinical
activity score (CAS), soft tissue involvement, pain, visual acuity, proptosis,
diplopia and reduction in eye movements. The secondary outcome was changes in
those individual parameters. Adverse effects were recorded at each visit.
RESULTS: A greater overall response rate was found in the MMF group compared with
the GC group at the 24th week (91.3% vs 67.9%, P = 0.000). MMF therapy showed a
better CAS response than GC (92.5% vs 70.5% improved, P < 0.05). Patients treated
with MMF showed a significantly improved rate of diplopia and proptosis than
patients treated with GC at the 24th week (90.4% and 68.8% improved,
respectively). Disease reactivation was not observed in the patients treated with
MMF but was observed in five patients after GC therapy. Adverse events occurred
in 4 of 80 patients treated with MMF (5%), all of which were mild to moderate. A
severe adverse event was only observed in one patient treated with GC but not at
all in patients treated with MMF. CONCLUSION: Compared with GC treatment, MMF
therapy is more effective and safer for patients with active moderate-to-severe
GO.
PMID- 27484050
TI - Antimicrobial Susceptibility Patterns of Clostridium difficile Isolates from
Family Dairy Farms.
AB - A significant risk factor for developing Clostridium difficile infection (CDI) in
humans and animals is associated with the antimicrobial use. It has often been
hypothesized that farm animals could be the source for human infection with
Clostridium difficile (CD). In the European Union, family-run dairy farms are the
predominant farming model, which are more interlinked within the community
compared to large-scale intensive dairy or beef farms. Therefore, it is important
to investigate antimicrobial susceptibility patterns of CD in such environment. A
total of 159 CD isolates from 20 family dairy farms were tested with a customized
broth microdilution plate for their antimicrobial resistance. Seventeen
antimicrobials were selected (amoxicillin, ceftriaxone, clindamycin, daptomycin,
erythromycin, fusidic acid, imipenem, levofloxacin, linezolid, metronidazole,
moxifloxacin, oxacillin, rifampicin, tetracycline, tigecycline,
trimethoprim/sulfamethoxazole and vancomycin), which are commonly used for
treatment of CDI in veterinary and human medicine, or were previously applied in
CD epidemiological studies. Antimicrobials, which are used for treatment of CDI
in humans (metronidazole, vancomycin, fusidic acid, tigecycline, linezolid)
inhibited CD growth in vitro. Most CD isolates were resistant to erythromycin
(93.1%), daptomycin (69.2%) and clindamycin (46.5%). High multiple-resistance was
found in CD ribotype 012 (n = 5, 100%), some CD SLO 060 (n = 4, 25%) and one CD
033 (n = 1, 1.1%). High multiple-resistance in this study was linked with CD
ribotypes and not with the origin of CD. The low prevalence of these ribotypes
(6.3%; 10/159) indicates that family-run dairy farms are an unlikely source of CD
with multiple-resistance to antimicrobials.
PMID- 27484051
TI - Angelman syndrome-derived neurons display late onset of paternal UBE3A silencing.
AB - Genomic imprinting is an epigenetic phenomenon resulting in parent-of-origin
specific gene expression that is regulated by a differentially methylated region.
Gene mutations or failures in the imprinting process lead to the development of
imprinting disorders, such as Angelman syndrome. The symptoms of Angelman
syndrome are caused by the absence of functional UBE3A protein in neurons of the
brain. To create a human neuronal model for Angelman syndrome, we reprogrammed
dermal fibroblasts of a patient carrying a defined three-base pair deletion in
UBE3A into induced pluripotent stem cells (iPSCs). In these iPSCs, both parental
alleles are present, distinguishable by the mutation, and express UBE3A. Detailed
characterization of these iPSCs demonstrated their pluripotency and exceptional
stability of the differentially methylated region regulating imprinted UBE3A
expression. We observed strong induction of SNHG14 and silencing of paternal
UBE3A expression only late during neuronal differentiation, in vitro. This new
Angelman syndrome iPSC line allows to study imprinted gene regulation on both
parental alleles and to dissect molecular pathways affected by the absence of
UBE3A protein.
PMID- 27484052
TI - Contrasting Frustrated Lewis Pair Reactivity with Selenium- and Boron-Based Lewis
Acids.
AB - The activation of pi-bonds in diynyl esters has been investigated by using soft
and hard Lewis acids. In the case of the soft selenium Lewis acid PhSeCl,
sequential activation of the alkyne bonds leads initially to an isocoumarin (1
equiv PhSeCl) and then to a tetracyclic conjugated structure with the isocoumarin
subunit fused to a benzoselenopyran (3 equiv PhSeCl). Conversely, the reaction
with the hard Lewis acidic borane B(C6 F5 )3 initiates a cascade reaction to
yield a complex pi-conjugated system containing phthalide and indene subunits.
PMID- 27484053
TI - Congenital heart defects in newborns with apparently isolated single
gastrointestinal malformation: A retrospective study.
AB - BACKGROUND: Congenital gastrointestinal system malformations/abdominal wall
defects (GISM) may appear as isolated defects (single or complex), or in
association with multiple malformations. The high incidence of association of
GISM and congenital heart defects (CHD) in patients with syndromes and
malformative sequences is known, but less expected is the association of
apparently isolated single GISM and CHD. The aim of this study was to investigate
the frequency of CHD in newborns with isolated GISM, and the possibility to
modify the diagnostic-therapeutic approach just before the onset of cardiac
symptoms or complications. METHODS: Anamnestic, clinical, and imaging data of
newborns requiring abdominal surgery for GISM, between 2009 and 2014, were
compared with a control group of healthy newborns. Distribution of GISM and
cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes
were identified. RESULTS: Seventy-one newborns with isolated GISM were included
in this study. More frequent GISM were intestinal rotation and fixation
disorders. CHD were observed in 15.5% of patients, augmenting their risk for
morbidity. Risk factors for morbidity related to sepsis were identified in
central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover,
28.2% of newborns presented only functional cardiac disorders but an unexpectedly
higher mortality. CONCLUSIONS: The high incidence of congenital heart disease in
infants with apparently isolated GISM confirms the need to perform an
echocardiographic study before surgery to improve perioperative management and
prevent complications such as sepsis and endocarditis.
PMID- 27484054
TI - Development and validation of a streamlined autism case confirmation approach for
use in epidemiologic risk factor research in prospective cohorts.
AB - The cost associated with incorporating standardized observational assessments and
diagnostic interviews in large-scale epidemiologic studies of autism spectrum
disorders (ASD) risk factors can be substantial. Streamlined approaches for
confirming ASD case status would benefit these studies. We conducted a multi
site, cross-sectional criterion validity study in a convenience sample of 382
three-year olds scheduled for neurodevelopmental evaluation. ASD case
classification as determined by three novel assessment instruments (the Early
Video-guided Autism Screener E-VAS; the Autism Symptom Interview, ASI; the
Screening Tool for Autism in Toddlers Expanded, STAT-E) each designed to be
administered in less than 30 minutes by lay staff, was compared to ADOS scores
and DSM-based diagnostic assessment from a qualified clinician. Sensitivity and
specificity of each instrument alone and in combination were estimated.
Alternative cutpoints were identified under different criteria and two-stage
cross validation was used to avoid overfitting. Findings were interpreted in the
context of a large, prospective pregnancy cohort study utilizing a two-stage
approach to case identification. Under initial cutpoints, sensitivity ranged from
0.63 to 0.92 and specificity from 0.35 to 0.70. Cutpoints giving equal weight to
sensitivity and specificity resulted in sensitivity estimates ranging from 0.45
to 0.83 and specificity ranging from 0.49 to 0.86. Several strategies were well
suited for application as a second-stage case-confirmation. These included the
STAT-E alone and the parallel administration of both the E-VAS and the ASI. Use
of more streamlined methods of case-confirmation in large-scale prospective
cohort epidemiologic investigations of ASD risk factors appears feasible. Autism
Res 2017, 10: 485-501. (c) 2016 International Society for Autism Research, Wiley
Periodicals, Inc.
PMID- 27484055
TI - Expression pattern of matrix metalloproteinases changes during folliculogenesis
in the cat ovary.
AB - Matrix metalloproteinase (MMP) has been implicated as having roles in ovarian
folliculogenesis. Here, we determined the expression pattern of six MMPs (MMP1,
MMP2, MMP3, MMP7, MMP9 and MMP13) and their endogenous tissue inhibitor, TIMP1,
during cat follicle growth. Different developmental stage follicles were
mechanically isolated and gene expression analysed by real-time qPCR while MMP1,
2, 9 and 13 localization was determined by immunohistochemistry. With the
exception of MMP13, the amount of MMP mRNA was lowest in primordial follicles and
increased thereafter. Peak levels were detected in early antral follicles for
MMP1 (72.2-fold increase above primordial follicle amount), MMP2 (10-fold), MMP3
(57-fold) and MMP9 (2.8-fold). MMP7 transcripts increased 2-fold by the primary
follicle stage and then plateaued. MMP13 mRNA peaked in primary follicles (2.5
fold) and was lower in more advanced counterparts. TIMP1 sharply increased (6
fold) in secondary follicles and gradually declined in the later stages. MMP1 and
MMP9 expression were expressed in the granulosa cells of all follicle stages.
MMP2 was immunoreactive in early and antral follicles, especially at granulosa
cells adjacent to the antral cavity. By contrast, the MMP13 was weakly detected
in primary follicles onward. In summary, there are distinctive and consistent
changes in MMPs and TIMP1 expression during follicle development, suggesting that
these enzymes play one or more roles in cat folliculogenesis. In particular, high
mRNA and protein expression levels of MMP1 and MMP2, especially at the antral
stage, indicate that these enzymes likely are involved in antrum formation and
expansion.
PMID- 27484056
TI - 1,3,4-Thiadiazole Based Anticancer Agents.
AB - In recent years, researchers like medicinal chemists in the field of medicinal
chemistry have widely utilized the 1,3,4-thiadiazole nucleus to investigate its
biological and pharmacological effects. This heterocyclic structure has
demonstrated various bioactivities such as antifungal, antimicrobial, antiviral,
antileishmanial, anti-inflammatory, antihypertensive, antiepileptic, and
anticancer effects among others. Anticancer activity is one of its promising
effect as five membered heterocyclic rings have widely been investigated by
researchers in the recent years. Herein, we reviewed the chemical structures
bearing 1,3,4-thiadiazole template exerting anticancer activity.
PMID- 27484058
TI - Building a More Diverse Workforce in HIV/AIDS Research: The Time has Come.
AB - Investigators from diverse racial and ethnic backgrounds are grossly
underrepresented in the nation's biomedical research enterprise. Projections of
current demographic trends suggest that population growth rates of minority
populations will outpace that of the Caucasian population by 2060. Thus, this
workforce will remain a poor reflection of the U.S. POPULATION: As a result of
this underrepresentation of all sectors of the U.S. populace, the majority of the
HIV research involving minority populations-those disproportionately impacted by
HIV infection-will be conducted by investigators who do not resemble them.
Although this does not necessarily preclude scientifically valid and important
research, it produces research without the important cultural and contextual
issues that can enhance the utility and generalizability of specific findings or
interventions. The goal of this review is to not only raise awareness of the
small numbers of minority investigators engaged in biomedical research, but also
to identify the challenges to recruiting and retaining these investigators. In
this article, while we discuss issues of diversity in general, the focus will be
upon the mental health aspects of the HIV epidemic for illustrative purposes: to
demonstrate the issues associated with enhancing investigator diversity as a
strategy for remediating the chronic shortage of historically underrepresented
investigators in scientific research. After presenting the magnitude of the
problem and a rationale for enhancing diversity of the biomedical research
workforce, we identify a number of potential reasons and challenges for the
shortage of minority investigators. Aspects of the mentoring process, together
with ten key suggestions, are discussed as the backdrop for the supplement papers
that follow (dealing with mentoring principles, challenges, and mentoring-related
issues on mentee, mentor, mentee-mentor relationship, and programs). By
identifying these realities we hope to: (1) promote greater discussions of these
challenges in academic institutions and settings; (2) suggest meaningful
strategies to address these challenges; and (3) foster a national discussion
about the long-term investment necessary for permanent change, as there are no
easy 'fixes' for these challenges.
PMID- 27484059
TI - Future HIV Mentoring Programs to Enhance Diversity.
AB - This paper proposes a general template to guide future mentoring program
development addressing: (i) considerations to ensure an adequate research
workforce; (ii) key guidelines and principles of mentoring; and (iii) use of a
logic model to develop program milestones, outcomes and evaluation. We focus on
these areas to guide and inform the most effective mentoring program components,
which we find to be more helpful than identifying specific features and
ingredients. Although the focus is on the development of a new generation of
investigators from diverse backgrounds, this template may also apply to mentoring
programs for other investigators and for disciplines beyond HIV.
PMID- 27484057
TI - Disrupted autophagy undermines skeletal muscle adaptation and integrity.
AB - This review assesses the importance of proteostasis in skeletal muscle
maintenance with a specific emphasis on autophagy. Skeletal muscle appears to be
particularly vulnerable to genetic defects in basal and induced autophagy,
indicating that autophagy is co-substantial to skeletal muscle maintenance and
adaptation. We discuss emerging evidence that tension-induced protein unfolding
may act as a direct link between mechanical stress and autophagic pathways.
Mechanistic links between protein damage, autophagy and muscle hypertrophy, which
is also induced by mechanical stress, are still poorly understood. However, some
mouse models of muscle disease show ameliorated symptoms upon effective targeting
of basal autophagy. These findings highlight the importance of autophagy as
therapeutic target and suggest that elucidating connections between protein
unfolding and mTOR-dependent or mTOR-independent hypertrophic responses is likely
to reveal specific therapeutic windows for the treatment of muscle wasting
disorders.
PMID- 27484060
TI - Mentoring the Mentors of Underrepresented Racial/Ethnic Minorities Who are
Conducting HIV Research: Beyond Cultural Competency.
AB - The majority of literature on mentoring focuses on mentee training needs, with
significantly less guidance for the mentors. Moreover, many mentoring the mentor
models assume generic (i.e. White) mentees with little attention to the concerns
of underrepresented racial/ethnic minorities (UREM). This has led to calls for
increased attention to diversity in research training programs, especially in the
field of HIV where racial/ethnic disparities are striking. Diversity training
tends to address the mentees' cultural competency in conducting research with
diverse populations, and often neglects the training needs of mentors in working
with diverse mentees. In this article, we critique the framing of diversity as
the problem (rather than the lack of mentor consciousness and skills), highlight
the need to extend mentor training beyond aspirations of cultural competency
toward cultural humility and cultural safety, and consider challenges to
effective mentoring of UREM, both for White and UREM mentors.
PMID- 27484061
TI - Exercise Promotion in Geriatric Oncology.
AB - Evidence of the benefits of exercise for people with cancer from diagnosis
through survivorship is growing. However, most cancers occur in older adults and
little exercise advice is available for making specific recommendations for older
adults with cancer. Individualized exercise prescriptions are safe, feasible, and
beneficial for the geriatric oncology population. Oncology providers must be
equipped to discuss the short- and long-term benefits of exercise and assist
older patients in obtaining appropriate exercise prescriptions. This review
provides detailed information about professionals and their roles as it relates
to functional assessment, intervention, and evaluation of the geriatric oncology
population. This review addresses the importance of functional status assessment
and appropriate referrals to other oncology professionals.
PMID- 27484062
TI - Immune Checkpoint Blockade: A New Era for Non-Small Cell Lung Cancer.
AB - Despite better understanding of it's molecular biology, non-small cell lung
cancer (NSCLC) remains a challenging disease to treat. Unfortunately, treatment
options are still very limited and prognosis for advanced disease is poor. Immune
surveillance plays a crucial role in a host's defence against tumour cells, and
this is particular relevant for lung cancer due to it's high somatic mutational
load, which increases the chances for the immune system to recognize cancer cells
as 'non-self'. Novel immunotherapies are emerging as an effective treatment for
this disease. In this review, we present the data on immune checkpoint inhibitors
for NSCLC, describing their mechanism of action, data efficacy from recent
clinical trials, and strategies to select patients more likely to benefit from
these agents.
PMID- 27484063
TI - Perifollicular blood flow and its relationship with endometrial vascularity,
follicular fluid EG-VEGF, IGF-1, and inhibin-a levels and IVF outcomes.
AB - PURPOSE: The aim of this study is to investigate the association of
perifollicular blood flow (PFBF) with follicular fluid EG-VEGF, inhibin-a, and
insulin-like growth factor-1 (IGF-1) concentrations, endometrial vascularity, and
IVF outcomes. METHODS: Forty women with tubal factor infertility were included in
a prospective cohort study. Each woman underwent IVF/ICSI procedure. Individual
follicles of >=16 mm (n = 156) were evaluated by power Doppler analysis and
categorized as well-vascularized follicles (WVFs) or poorly vascularized
follicles (PVFs). WVFs referred to those with perifollicular vascularity of 51
100 %. Each follicular fluid (FF) was individually aspirated and FF/serum EG
VEGF, inhibin-a, and FF IGF-1 levels were evaluated. Zones III-IV endometrial
vascularity was classified as a well-vascularized endometrium (WVE). The presence
of a WVE and mature oocytes, in addition to the embryo quality and clinical
pregnancy rate (CPR), were recorded for each follicle. The main outcome measures
were FF serum EG-VEGF, inhibin-a, IGF-1 levels, and WVE and IVF outcome per PFBF.
RESULTS: For WVFs, the level of FF EG-VEGF (p = 0.008), oocyte quality (p =
0.001), embryo quality (p = 0.002), a WVE (p = 0.001), and CPR (p = 0.04)
increased significantly. The pregnant group was characterized by increased
numbers of WVFs (p = 0.044), a WVE (p = 0.022), and increased levels of FF IGF-1
(p = 0.001) and serum EG-VEGF (p = 0.03). FF IGF-1 >50 ng/mL (AUC 0.72) had 75 %
sensitivity and 64 % specificity for predicting CPR. CONCLUSIONS: WVFs yield high
quality oocytes and embryos, a WVE, increased FF EG-VEGF levels, and increased
CPRs.
PMID- 27484064
TI - Hepatocellular carcinoma with gastric metastasis treated by simultaneous hepatic
and gastric resection: report of a case.
AB - Hepatocellular carcinoma (HCC) with gastric metastasis is extremely rare. There
have been few reports on curative surgical resection for gastric metastasis of
HCC. We herein report such a case successfully treated by simultaneous surgical
resection. A 73-year-old male was admitted for evaluation and treatment of a
liver tumor. Computed tomography showed an exophytic tumor of 170 mm in diameter
located in the left lobe of the liver with poor delineation to the gastric wall.
Upper gastrointestinal endoscopy revealed a submucosal tumor with ulceration in
the antrum of the stomach. With a diagnosis of HCC with invasion to the gastric
wall, an en bloc resection was planned, and the patient underwent laparotomy. The
patients underwent left hemihepatectomy with partial resection of the stomach for
adhesion and distal gastrectomy for the tumor. Pathological examination of the
liver tumor revealed poorly differentiated HCC, and pathological diagnosis of the
tumor in the submucosal and muscular layer of the stomach was compatible with
metastasis from HCC, which was separate from the liver tumor. Therefore, we
diagnosed the tumor as HCC with hematogenous gastric metastasis. The patient
remains well with no evidence of tumor recurrence as of 13 months after
resection.
PMID- 27484065
TI - Cultural variation in antismoking video ads between the United States, Taiwan,
and China.
AB - Antitobacco advertisement components, including types of messages and advertising
appeals, have not been evaluated among multinational groups. This study
identified and compared the content of antismoking video ads across three
countries. We reviewed 86 antismoking video advertisements for the following
information: severity of the consequences of smoking, types of risks, appeals to
audiences' self-efficacy, benefits of not smoking, targeted social-ecological
level and types of message appeal used. Two researchers independently coded each
advertisement with an average inter-coder reliability of 0.79.Analyses showed a
variety of focuses: smoking-related health risks (86%), severe consequences of
smoking (54.7%), self-efficacy beliefs (40.7%) and benefits of not smoking
(84.9%). Compared to the United States and Taiwanese ads, Chinese ads were more
likely to target at the community level (10% versus 23.3% versus 47.2%).
Additionally, 55% of the United States ads used the fear approach, whereas 61.1%
of Chinese ads used the social approach. Taiwanese ads were evenly distributed
among both approaches. In conclusion, the countries used different targeting
strategies and approaches during message delivery. Although China's neighboring
country, Taiwan, has many similar cultural aspects, including the same language,
they are greatly influenced by US antitobacco campaigns. As a result, Taiwan's
tobacco campaigns appear to have similar components to both China and the United
States. Further research is warranted to understand the reasons for each method
and to examine the effectiveness of the ads in reducing smoking rates.
PMID- 27484066
TI - Mesenchymal stem cells attenuate ischemia-reperfusion injury after prolonged cold
ischemia in a mouse model of lung transplantation: a preliminary study.
AB - PURPOSE: Mesenchymal stem cells (MSCs) suppress inflammation and immune
responses. We conducted this study to find out if MSCs attenuate ischemia
reperfusion injury in a mouse model of lung transplantation. METHODS: C57BL/6J
mouse lungs perfused with low-potassium dextran glucose solution were preserved
at 4 degrees C for 18 h. Human MSCs were slowly injected into the left pulmonary
artery of the lung grafts, and orthotopic left lung transplantation was then
performed. The lung isografts were reperfused for 6 h, and bronchoalveolar lavage
fluid (BALF) from the left lung graft was collected. We measured the protein
concentration, cell count, and proinflammatory cytokine concentrations in the
BALF. RESULTS: The protein concentration and cell count in the BALF were
significantly lower in the MSC-administered grafts than in the PBS-administered
controls. Concentrations of proinflammatory cytokines, including IL-1beta, IL
17A, and TNF-alpha, in BALF tended to be lower in the MSC-administered grafts
than in the controls, but the difference was not significant. CONCLUSION: The pre
transplant administration of MSCs via the pulmonary artery of the lung graft
attenuated ischemia-reperfusion injury after prolonged cold ischemia in this
mouse model of lung transplantation.
PMID- 27484067
TI - Does segmentectomy really preserve the pulmonary function better than lobectomy
for patients with early-stage lung cancer?
AB - PURPOSE: Recently, segmentectomy has been considered as an alternative to
lobectomy in early peripheral non-small lung cancer (NSCLC); however, controversy
has remained regarding the long-term functional advantage after segmentectomy.
The aim of this study was to analyze the postoperative lung function after
segmentectomy and lobectomy for non-small cell lung cancer. METHODS: Patients
with p-T1aN0M0 NSCLC who had undergone segmentectomy (n = 37) or lobectomy (n =
33) were retrospectively analyzed. The ratios of postoperative to preoperative
forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were
defined as the recovery rates. The radiological lung volume and weight were
evaluated before and more than 6 months after surgery, and the postoperative
values were compared with the predicted values that were calculated from the
preoperative values, subtracting the resected lobes or segments. RESULTS: The
clinical characteristics, including the preoperative lung function showed no
significant differences between the groups. No statistical differences were
recognized in the trend lines for recovery ratios of FVC and FEV1.0 (P = 0.96 and
P = 0.33). The recovery ratios for radiologic lung volume and weight showed no
significant differences (P = 0.46 and P = 0.22). The postoperative lung volume
and weight were almost the same as the predicted values after segmentectomy,
whereas those after lobectomy were significantly higher than the predicted
values. CONCLUSIONS: No functional advantage for segmentectomy was observed
during long-term follow-up, possibly due to compensatory lung growth after
lobectomy.
PMID- 27484069
TI - Functional study of the upregulation of miRNA-27a and miRNA-27b in 3T3-L1 cells
in response to berberine.
AB - Berberine is the major active component of Rhizoma Coptidis derived from a
traditional Chinese herbal medicine and is known to regulate micro (mi)RNA
levels, although the mechanism for this action remains unknown. The present study
confirmed that treatment of 3T3-L1 cells with berberine inhibited cell viability
and differentiation in a dose- and time-dependent manner, and significantly
increased the mRNA expression levels of miRNA-27a and miRNA-27b. In addition, in
3T3-L1 cells treated with berberine, overexpression of miRNA-27a and miRNA-27b
improved the berberine-mediated inhibition of cell differentiation and reduction
of triglyceride contents. By contrast, miRNA-27a and miRNA-27b inhibitors
attenuated the berberine-mediated inhibition of cell differentiation and
reduction of triglyceride contents. Additionally, peroxisome proliferator
activated receptors (PPAR)-gamma was confirmed to be a target of miRNA-27a in the
3T3-L1 cells. A dual-luciferase reporter assay indicated that the expression of
PPAR-gamma was negatively regulated by miRNA-27a. These findings may provide
novel mechanistic insight into the antiobesity effects of certain compounds in
traditional Chinese herbal medicine.
PMID- 27484070
TI - Standard Approaches to the Acetabulum Part 1: Kocher-Langenbeck Approach.
AB - Historically, standard approaches for surgical treatment of displaced acetabular
fractures were the KocherLangenbeck approach, the ilioinguinal approach and the
extended iliofemoral approach (12). Presently, several modifications of these
approaches are accepted alternatives, especially anterior modifications based on
the intrapelvic approach described by Hirvensalo (8). Single access approaches
allowing visualization of one acetabular column are the posterior Kocher
Langenbeck approach and the anterior ilioinguinal approach (12) and the use of a
single approach is favoured (9, 24). For more complex situations, in the 80s and
90s extended approaches (extended iliofemoral approach according to Letournel
(12), its modification to Reinert (19) (Baltimore approach), and the Triradiate
approach according to Mears (14)) were introduced. These approaches are presently
rarely choosen due to the extensive soft tissue dissection and higher
complication rates (28). Alternatively, the combination of an anterior and
posterior standard approach was recommended (7, 21, 22) having the disadvantage
of longer operating time and blood loss and showed no superior results compared
to a single approach. The meta-analysis by Giannoudis et al. stated that 48,7% of
patients were treated using the Kocher-Langenbeck approach, followed by 21,9%
ilioinguinal approaches and 12,4% extended approaches (6). More recent data from
the years 2005-2007, showed that anterior approaches are now predominantly used
according to a higher number of acetabular fractures with anterior column
involvement. Overall, more than 40% of all patients with acetabular fractures are
still approached via the Kocher-Langenbeck approach (18). Therefore, the Kocher
Langenbeck approach is still a "working horse" in approaching displaced
acetabular fractures. The Kocher-Langenbeck approach consists of two parts. In
1874 von Langenbeck described a longitudinal incision starting from above the
greater sciatic notch to the greater trochanter, dissecting the gluteal muscles
for treating hip joint infections (11). Theodor Kocher in 1911 described a curved
incision starting from the posterior-inferior corner of the greater trochanter,
running across the postero-superior tip of the greater trochanter passing oblique
in line with the fibres of the gluteus maximus muscle in direction to the
posterior superior iliac spine (10). The aim of the present analysis is the
detailed anatomi - cal analysis of this standard approach, focusing on fracture
indication, positioning of the patient, exposure, dissection, reduction
techniques of special fracture types, approach modifications/extensions,
complications and approach-specific results.
PMID- 27484068
TI - S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine
Bronchopulmonary Dysplasia.
AB - Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung
disease and profound, refractory bronchospasm. It is observed among survivors of
premature birth who have been treated with prolonged supplemental oxygen.
Therapeutic options are limited. Using a neonatal mouse model of BPD, we show
that hyperoxia increases activity and expression of a mediator of endogenous
bronchoconstriction, S-nitrosoglutathione (GSNO) reductase. MicroRNA-342-3p,
predicted in silico and shown in this study in vitro to suppress expression of
GSNO reductase, was decreased in hyperoxia-exposed pups. Both pretreatment with
aerosolized GSNO and inhibition of GSNO reductase attenuated airway
hyperresponsiveness in vivo among juvenile and adult mice exposed to neonatal
hyperoxia. Our data suggest that neonatal hyperoxia exposure causes detrimental
effects on airway hyperreactivity through microRNA-342-3p-mediated upregulation
of GSNO reductase expression. Furthermore, our data demonstrate that this adverse
effect can be overcome by supplementing its substrate, GSNO, or by inhibiting the
enzyme itself. Rates of BPD have not improved over the past two decades; nor have
new therapies been developed. GSNO-based therapies are a novel treatment of the
respiratory problems that patients with BPD experience.
PMID- 27484071
TI - [Minimal Invasive Fixation of Pelvic Injury: CT-Study of the Pelvic Bone
Dimensions].
AB - PURPOSE OF THE STUDY This radiographic study was focused on measuring the
dimensions of pelvic bones at sites of minimally invasive screw insertion with
the aim to assess the risk of damage to vascular and nervous structures. MATERIAL
AND METHODS The group consisted of 77 patients (39 women and 38 men) aged between
19 and 85 years (average, 65; women, 65; men, 64) who underwent CT examination of
the pelvis because of reasons other than injury. On the left side, a total of 14
dimensions of the superior pubic ramus, supraacetabular region, retroacetabular
region, quadrilateral surface of the acetabulum and lateral foraminal sides of
the S1 and S2 vertebral bodies were measured. The results were evaluated using
descriptive statistics. RESULTS The inner antero-posterior dimension of the
isthmic area of the superior pubic ramus was 8 mm or less in four women (10.3%)
and 9 or 10 mm in further 14 women (35.9%). The inner cranio-caudal dimension of
the superior pubic ramus was 8 mm or less in 14 women (35.9%) and 9 or 10 mm in
further 16 women (41.0%). These dimensions obtained in men were as follows: 8 mm
and less in three men (7.9%) (7 mm in one, 8 mm in two), and 9 or 10 mm in nine
men. Sizes of the other pelvic bones were large enough to allow for safe
insertion of single screws. DISCUSSION Single screws most frequently used in
minimally invasive treatment of pelvic fractures are cannulated screws 7.3 mm or
6.5 mm in diameter; less frequently used are 4.5-mm cancellous screws (e.g. in
treatment of avulsion injuries) or long 3.5-mm cortical "creeping" screws to be
inserted in the superior pubic ramus. The use of "creeping" screws reported by
several authors indicates problems associated with placement of standard screws
(diameter, 7.3 mm and 6.5 mm) through the isthmus into the superior ramus. In
slim high pelvises of some patients with gracile skeletons or in low pelvises of
small women, the screws can protrude over the cortical margin. However, the risk
of injury to nervous or vascular structures is low when the intraosseous screw is
exactly inserted and it is so even in case its thread cuts into cortical bone.
Neither the femoral artery nor the femoral nerve is situated too close to the
superior pubic ramus. The "corona mortis" may potentially be jeopardised because
of its contact with both the superior and posterior cortical bones of the
superior ramus, but it usually follows a course more lateral to the isthmus of
the ramus. CONCLUSIONS The results of the study showed that the size of the
superior pubic ramus in its isthmic area may cause difficulties during insertion
of cannulated screws with standard diameters (7.3 mm and 6.5 mm) in the majority
of women and in some men. The risk of damage to vascular and nervous structures
during screw insertion is associated only with the superior and posterior walls
of the superior pubic ramus and with the area of the S2 foramen in case the
correct procedure of intraosseous screw insertion is not strictly followed. KEY
WORDS: retrograde pubic screw, iliosacral screw, supraacetabular screw,
retrograde posterior column screw.
PMID- 27484072
TI - [Analysis of Oxidative Damage to Components Removed from Beznoska/Poldi Total Hip
Replacements].
AB - PURPOSE OF THE STUDY Ultrahigh molecular weight polyethylene (UHMWPE) is today
the most frequently used bearing surface in total joint replacements (TJR)
because of its properties, i.e., excellent biocompatibility, good mechanical and
tribological performance and high wear resistance. UHMWPE liners are the most
loaded TJR components and, therefore, their properties are decisive for TJR
longevity. This study had three objectives: 1) to evaluate the oxidative
degradation of explanted UHMWPE components; 2) to look for a statistically
significant relationship between the extent of oxidative degradation and the
durability of joint replacements; and 3) to investigate whether the durability of
a TJR was related to the type of sterilisation used in manufacture. MATERIAL AND
METHODS The study included 26 acetabular components obtained at revision
arthroplasty between 2004 and 2013 from patients in whom a Beznoska/Poldi total
hip replacement was used in the period from 1977 to 2002. The average age of the
patients at the time of primary implantation was 57.9 years, the average
longevity of the components removed was 18.63 years (range, 6.9 to 27.9 years).
Samples of worn out and unworn areas from explanted components were processed in
a three-step procedure in order to finally obtain 2-mm microtome sections. These
were studied by infrared microspectroscopy. Oxidative damage to UHMWPE was
determined as the oxidation index (OI); radiation damage to UHMWPE during
sterilization was evaluated as the transvinylene index (VI); oxidation-induced
changes in the polymer structure and its properties were characterised as the
crystallinity index (CI); and local changes in mechanical properties due to
oxidative degradation were assessed as microhardness (MH). Spearman's correlation
coefficient and the Wilcoxon two-sample test were used for statistical analysis.
RESULTS The OI values (average and maximum) in both worn out and unworn surface
areas were related to component longevity. The difference between the oxidation
index of ruptured components and that of the other components was statistically
significant. Significant differences were also found between the average and
maximum OI values of worn out areas and those of unworn surfaces. The
relationship between the average oxidation index in both the unworn and worn out
areas of UHMWPE components and the longevity of cracked components was
statistically significant. DISCUSSION Our results show that the OI values
obtained by microspectroscopy correlated with both the microscopic damage and the
longevity of UHMWPE liners and the correlation was statistically significant also
in relation to the longevity of total replacements. Relationships amongst OI, VI,
CI and MH values as well as their relation to failure and longevity of total
replacements are discussed. CONCLUSIONS It can be concluded that infrared
microspectroscopic measurement of OI values is a simple and fast method to
characterise UHMWPE liners. In addition, the IR spectra also show other
supplementary characteristics, such as VI and CI indices. These values provide
information on the quality of various UHMWPE types currently used in TJR surgery.
The types of UHMWPE which exhibit high oxidative degradation should be avoided in
clinical practice due to increased risk of early TJR failure. Responsible
orthopedic surgeons should be aware of this fact and, if possible, collaborate
with an independent, noncommercial laboratory in order to evaluate the quality of
various UHMWPE liners used in their hospitals. KEY WORDS: UHMWPE, oxidation,
total joint replacement, infrared spectroscopy, microhardness.
PMID- 27484073
TI - [Alloplastic Materials and their Propensity to Bacterial Colonisation].
AB - PURPOSE OF THE STUDY The alloplastic materials currently used for protective
surface layers on implants were tested in vitro under microbiological laboratory
conditions by contamination with microbial agents most frequently found in deep
infection of total joint replacements. The objective was to find out how the
resistance to bacterial colonisation was related to different surface finishes.
MATERIAL AND METHODS Each of 14 samples of alloplastic material currently used in
the manufacture of orthopaedic implants was inoculated with each of the group of
microorganisms most frequently infecting joint replacements; these were
Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa,
Enterococcus faecalis and Escherichia coli. At 24 hours of incubation, biofilms
produced on sample surfaces were collected, stained with crystalline violet and
assessed by spectrophotometry. The average value of biofilm absorbances (AV595)
for the group of microorganism tested was taken as a basic characteristic of each
material sample indicating its sensitivity to bacterial. RESULTS Of the metal
materials with smooth surface finish, Vitalium (AV595, 0.368) showed the lowest
affinity to microbial colonisation; next was titanium (AV595, 0.459) and steel
(AV595, 0.505). A significant increase in sensitivity to bacterial colonisation
was recorded in all types of surface finish of steel (AV595, 0.571) and in
titanium alloy with a rough surface texture (AV595, 0.737 to 1.676); p < 0.05.
Porous titanium surfaces significantly increased material affinity to
colonisation. DISCUSSION Our study had certain limitations concerning in vitro
evaluation of porous surfaces that have high affinity to bacterial colonisation.
Porous titanium, and its hydroxyapatite layer in particular, considerably
promotes osteoblast colonisation of the surface as well as implant
osseointegration in the bone bed. Microorganisms therefore have no room for
surface colonisation. Problematic may remain the surface parts outside contact
with bone that keep their affinity to bacterial colonisation. CONCLUSIONS The
material of choice for cemented implants is Vitalium which, of all metal
surfaces, has the lowest sensitivity to bacterial colonisation. The materials of
choice for cementless implants are titanium alloys. However, an osteoactive
surface not in contact with bone remains a problem. On the one hand, its
roughness and porosity are crucial to good osseointegration, on the other hand,
its affinity to bacterial colonisation is high. KEY WORDS: alloplastic material,
biofilm, joint replacement infection.
PMID- 27484074
TI - [Management of Osteochondral Lesions of the Ankle Joint by Implantation of
Autologous Chondrocytes].
AB - PUPOSE OF THE STUDY The treatment of osteochondral lesions of weight-bearing
joints remains a serious therapeutic challenge, largely due to the minimal
ability of articular hyaline cartilage to regenerate. The authors present the
long-term clinical and MRI results of treating deep chondral and osteochondral
defects of the ankle joint by the method of implantation of autologous
chondrocytes in the form of a solid chondrograft. MATERIAL AND METHODS The method
of solid chondrograft implantation in the ankle joint was used in our Department
from the year 2003. Between 2003 and 2013, this method was used in 31 patients,
16 men and 15 women. Their average age at the time of implantation was 29 years
(16 to 50 years). The follow-up period ranged from 16 to 145 months (average, 57
months). The clinical outcome was evaluated using the Mazur questionnaire. At
follow-up all patients underwent regular MRI examinations and the results were
assessed on the basis of Magnetic Resonance Observation of Cartilage Repair
Tissue (MOCART) scores. Twelve patients required a second-look arthroscopy.
RESULTS A comparison of the Mazur pre-operative scores with those obtained at 1,
2 and 5 years post-operatively showed marked improvement of ankle joint function.
The average pre-operative value of 30.0 (based on responses of 31 patients)
increased to the average of 89.7 (based on results of 11 patients). At 1 year
post-operatively, the average MOCART score for a group of 18 patients was 78.3;
at 5 post-operative years, the average value for nine patients examined was 77.0.
Complete filling of defects at 1 year of follow-up was found in 88.1% and , at 5
years, it was recorded in 83.3% of the patients examined. DISCUSSION The
articular hyaline cartilage is a highly differentiated tissue and its ability of
repair is very limited. Therefore every damage to the articular surface should be
regarded as a pre-arthritic condition// disease. Currently, there are several
options of treating a damaged articular cartilage, but none of them makes its
complete healing certain. A lot of studies concerned with longterm results of
implanting autologous chondrocytes in the knee are available in the literature,
but only few authors present long-term clinical and radiographic outcomes of
ankle joint treatment similar to ours. CONCLUSIONS Based on our clinical and MRI
results, the method of autologous chondrocyte implantation can be recommended
since it has good long-term results, provides repair of articular cartilage and
allows for patients' return to activities of daily living. KEY WORDS: chondral
defect, hyaline cartilage, autologous chondrocyte, ankle joint.
PMID- 27484075
TI - [Use of Patient Specific Instruments at Total Knee Arthroplasty. One-Year Results
of a Prospective Randomised Study].
AB - PURPOSE OF THE STUDY The aim of this prospective study was to evaluate, at one
year of follow-up, radiographic and clinical results of total knee arthroplasty
(TKA) performed with use of Zimmer(r) Patient Specific Instruments (PSIs) which
allow for planning and customising each patient's TKA. MATERIAL AND METHODS Of
the patients with knee arthritis who were eligible for joint replacement, 23 were
randomly selected and included in this study. There were 11 men and 12 women,
with 11 right and 12 left knee joints. On the basis of pre-operative CT scans,
PSI custom-made pin guides, which conformed to the individual patient's anatomy,
were produced and then used in the THA surgery involving a NexGen (CR) system.
All patients were examined before surgery and at 1 year after THA. The evaluation
at a follow-up visit included standing full-length radiographs (antero-posterior
and lateral), Knee Score results, range of motion (ROM), patient's satisfaction
report, and post-operative complications. The X-ray views were examined for
mechanical leg axis alignment, TKA alignment in antero-posterior and lateral
projection and signs of potential loosening. RESULTS At 1 post-operative year,
the average Knee Society Score (KSS) was 85.5 points and the average functional
score was 82.6 point. The satisfaction rate was 94% and, on a school rating
system, the average mark was 1.3. The average postoperative ROM value was 116
degrees . All patients were willing to undergo the surgery again. The only
complication was thrombosis in one patient. Radiographic findings of knee
alignment were optimal in 18, correct (up to 3 degrees deviation) in three and
incorrect (above 3 degrees deviation) in two patients. Radiographic signs of
loosening were not recorded. DISCUSSION Correct knee alignment is one of the
requirements for achieving a good TKA outcome. Various techniques are used to
improve the total knee process (computer-aided surgery, customised guides).
Zimmer Patient Specific Instruments provide advanced pre-operative planning and
more accurate implant sizing and alignment. An experienced surgeon can achieve
the same good results with conventional planning under standard conditions but
the use of PSIs is clearly more beneficial in patients with extra-articular
deformities and in patients in whom femoral intramedullary guides cannot be
employed. To produce a custom-made pin guide requires a CT scan of the whole leg
and is also associated with additional paperwork. The PSIs simplify the total
knee process from start to finish and surgeons have complete flexibility to make
fine-tuning adjustments during the procedure. CONCLUSIONS Zimmer Patient Specific
Instruments allow for exact alignment of both the femoral and the tibial
component in a TKA process. Under standard circumstances, clinical and
radiographic outcomes are comparable with those of conventional planning.
However, the use of PSIs is clearly more beneficial in patients with extra
articular deformities and in patients in whom femoral intramedullary guides
cannot be employed. KEY WORDS: total knee arthroplasty, TKA, Patient Specific
Instruments, PSIs.
PMID- 27484076
TI - [Positions of Sustentacular Screw in Osteosynthesis of Calcaneal Fractures:
Clinical and Radiographic Study].
AB - PURPOSE OF THE STUDY The aim of the study was to analyse the options for
sustentacular screw placement in osteosynthesis of intra-articular fractures of
the heel bone and to assess the effect of various screw positions on failure to
maintain the reduction in the postoperative period. In addition, problems related
to screw-end protrusion over the medial cortical bone or to screw penetration
into the talocalcaneal joint were assessed. MATERIAL AND METHODS The group
comprised 23 patients with a total of 25 intra-articular fractures of the heel
bone treated by surgery. The procedure involved insertion of a sustentacular
screw under fluoroscopic guidance. Post-operatively, screw position in the
sustentacular fragment was evaluated on CT scans. During follow-up, attention was
focused on the effect of screw placement on maintenance of fracture reduction,
and clinical symptoms potentially associated with screw malposition were
recorded. RESULTS All sustentacular screws were fixed sustentacular fragments.
Seven screws (28%) were inserted in the talar shelf, seven (28%) were placed
under and nine (36%) over the sustentaculum tali. Two screws penetrated into the
talocalcaneal joint (8%). The end of a screw projecting by 2 mm over the medial
wall of the calcaneus was found in 11 cases (44%). Two patients with screws
penetrating into the talocalcaneal joint had problems. On the other hand, no
clinical effect of a screw extending over the medial wall of the calcaneus was
recorded. No significant association of screw position with late //delayed
failure of fracture reduction was detected. DISCUSSION Although the ideal
trajectory for a sustentacular screw have been defined using a model of the
calcaneus, it is not easy to achieve optimal screw placement due to the complex
anatomy of the calcaneus and limited possibilities of intra-operative control of
screw insertion. Any sustentacular screw malposition is a potential risk factor,
particularly if the screw has penetrated into the talocalcaneal joint. Therefore,
it will be useful to seek methods allowing for safer screw insertion and
elimination of risks associated with screw misplacement. The technique of
sustentacular screw insertion by means of a compression-based device, described
by the authors, designated to allow for screw placement in distal humerus
fractures is one of the options. CONCLUSIONS Optimisation of techniques for
sustentacular screw insertion in the osteosynthesis of calcaneal fractures should
contribute to reduction of risks related to screw malposition. The assessment of
effects which the position of a screw may have on delayed failure of fracture
reduction should be based on a thorough biomechanical study. KEY WORDS:
sustentacular screw, calcaneal fracture, insertion, malposition.
PMID- 27484077
TI - Eastbourne Miami-J Protocol: a Pilot Study for the Care of Cervical Injuries in
the Community.
AB - PURPOSE OF THE STUDY The aim of this pilot study was to develop The Eastbourne
Miami-J Protocol for care of cervical injuries within the community. Led by
orthopaedic senior practitioners, a multidisciplinary approach was developed to
provide education and collar care for patients on a weekly basis. MATERIALS AND
METHODS A total of 51 patients (17 male and 33 female), mean age 74 years (21 to
95) with CT confirmed cervical injuries during November 2010 and May 2014
followed the Eastbourne Miami-J Protocol. RESULTS Patients required collar care
on average for 7.25 weeks. Thirty-two patients had single level cervical injuries
with C2 the commonest. Complications included: 6 patients with psychosocial
issues; 10 patients with skin erythema due to ill-fitting collars and 2 patients
with skin breakdown requiring dressings. CONCLUSION The Eastbourne Miami-J
protocol demonstrates that a multidisciplinary approach, championed by the
casting department, can provide care for patients with cervical injuries within
the community. KEY WORDS: cervical spine, C-spine, cervical collar, community,
rehabilitation.
PMID- 27484078
TI - [Giant Ganglioneuroma of the Spine and Mediastinum].
AB - The case of a 15-year-old girl with a large ganglioneuroma in the mediastinum and
spinal canal is presented. The tumour initially manifested as scoliosis. Its
diagnosis was made on the basis of CT scanning and magnetic resonance imaging,
and confirmed by thoracoscopic mediastinal biopsy. Radical tumour excision was
indicated. The first stage involved removal of the tumour from the spinal canal
through a posterior approach, and transpedicular fixation of the spinal column
with correction of the curve. At the second-stage procedure, the tumour was
removed from the pleural cavity and mediastinum through thoracotomy. At two years
after surgery, the spondylodesis was completed with autologous bone grafts that
healed within 6 months. At 3-year follow-up the patient was with neither clinical
findings, nor subjective complains and imaging methods showed no signs of tumour
recurrence. KEY WORDS: ganglioneuroma, scoliosis, correction, thoracotomy, spinal
canal, mediastinum.
PMID- 27484079
TI - [Isolated Displaced Fracture of the Acromion - Case Report].
AB - Displaced fractures of the acromion are rare injuries. A 45-year-old lady
presented with an isolated acromion fracture (type III, Kuhn classification)
resulting from a direct blow to the top of her right shoulder in a fall while
skiing. After standard clinical and radiological examination of the shoulder, an
open reduction and internal plate fixation using a postero-superior approach to
the scapula was performed. Early rehabilitation of the arm and shoulder was
initiated. At 50 days after surgery the patient achieved a full range of motion
in her right shoulder and muscle strength equal to that of the contralateral
extremity. By 12 weeks radiographic union of the fracture was recorded. The final
functional outcome after open reduction and internal plate fixation of the
fracture was comparable with results reported in the literature and, in
comparison with conservative treatment, the risk of non-union was significantly
reduced. KEY WORDS: acromion fracture, scapula, osteosynthesis.
PMID- 27484080
TI - [Generalised Form of Synovial Chondromatosis of the Knee Joint].
AB - This study describes a diagnostic and therapeutic algorithm in a 53-year-old male
patient who was diagnosed with a synovial chondromatosis of the knee joint
extending to the popliteal fossa and soft tissues around the knee. Because of the
presence of massive nodules, the patient was indicated for total synovectomy,
with removal of pathologically changed cartilaginous tissue, performed by
combined anterior and posterior approaches to the knee joint. Despite complete
removal of the synovium and loose cartilage bodies and the patient's pain relief
in the post-operative time, three years after the operation new problems
appeared. Magnetic resonance imaging (MRI) confirmed a relapse of synovial
chondromatosis and the patient was indicated for revision surgery of the knee
joint. The results of physical examination and MRI scans, and intra-operative
findings in the patient are reported. KEY WORDS: synovial chondromatosis, total
synovectomy, direct anterior and posterior approaches to the knee joint.
PMID- 27484081
TI - Insurance-related disparities in primary care quality among U.S. Type 2 diabetes
patients.
AB - BACKGROUND: This study explored insurance-related disparities in primary care
quality among Americans with type 2 diabetes. METHODS: Data came from the
household component of the 2012 Medical Expenditure Panel Survey (MEPS). Analysis
focused on adult subjects with type 2 diabetes. Logistic regressions were
performed to investigate the associations between insurance status and primary
care attributes related to first contact, longitudinality, comprehensiveness, and
coordination, while controlling for confounding factors. RESULTS: Preliminary
findings revealed differences among three insurance groups in the first contact
domain of primary care quality. After controlling for confounding factors, these
differences were no longer apparent, with all insurance groups reporting similar
primary care quality according to the four domains of interest in the study.
There were significant differences in socioeconomic status among different
insurance groups. CONCLUSION: This study reveals equitable primary care quality
for diabetes patients despite their health insurance status. In addition to
insurance-related differences, the other socioeconomic stratification factors are
assumed to be the root cause of disparities in care. This research emphasizes the
crucial role that primary care plays in the accessibility and quality of care for
chronically ill patients. Policy makers should continue their commitment to
reduce gaps in insurance coverage and improve access as well as quality of
diabetic care.
PMID- 27484082
TI - A phase III, multi-centre, double-masked randomised controlled trial of
adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus
standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma
(ASCOT): statistical analysis plan.
AB - BACKGROUND: Open globe ocular trauma complicated by intraocular scarring
(proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially
treatable condition for which, at present, surgery is often unsatisfactory and
visual results frequently poor. To date, no pharmacological adjuncts to surgery
have been proven to be effective. The aim of the Adjunctive Steroid Combination
in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether
adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can
improve the outcome of vitreoretinal surgery in patients with open globe ocular
trauma. This article presents the statistical analysis plan for the main
publication as approved and signed off by the Trial Steering Committee prior to
the first data extraction for the Data Monitoring Committee meeting report.
METHODS/DESIGN: ASCOT is a pragmatic, multi-centre, parallel-group, double-masked
randomised controlled trial. The aim of the study is to recruit from 20-25
centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two
treatment arms. Both groups will receive standard surgical treatment and care;
the intervention arm will additionally receive a pre-operative steroid
combination (triamcinolone acetonide) into the vitreous cavity consisting of 4
mg/0.1 ml and 40 mg/1 ml sub-Tenon's. Participants will be followed for 6 months
post-surgery. The primary outcome is the proportion of patients achieving a
clinically meaning improvement in visual acuity in the study eye at 6 months
after initial surgery, defined as a 10 letter score improvement in the ETDRS (the
standard scale to test visual acuity). TRIAL REGISTRATION: ISRCTN30012492 .
Registered on 5 September 2014. EudraCT2014-002193-37 . Registered on 5 September
2014.
PMID- 27484083
TI - The best time for surgery on a patient with recurrent pneumothorax and
undetectable culprit lesions is at the exact time air leakage is discovered: a
case report.
AB - BACKGROUND: One cause of recurrent spontaneous pneumothorax includes overlooking
bullae during a previous surgery for pneumothorax; and the identification of the
culprit lesions is necessary for prevention of recurrence. CASE PRESENTATION: A
28-year-old man was referred to our hospital because of spontaneous right-sided
pneumothorax. He underwent video-assisted thoracoscopic surgery, which did not
reveal air leakage. The patient was subsequently seen at our hospital for 2
additional episodes of recurrent right-sided pneumothorax. At the third admission
we observed intermittent air leakage while the patient was in the sitting
position after chest drainage, and we performed surgery. An intraoperative
submersion test showed air leakage dorsally from the pleural surface of S(6) and
a minute culprit lesion, which were not seen at the first operation and confirmed
the leakage site. The area was ligated and coated with regenerated oxidized
cellulose mesh and autologous blood. CONCLUSION: In cases of pneumothorax with
repeated recurrence, the best time to perform surgery on the patient with
undetectable culprit lesion is the exact time that air leakage is observed.
PMID- 27484085
TI - Risk factors associated with intestinal parasitic infections among inmates of
Kisii prison, Kisii county, Kenya.
AB - BACKGROUND: Intestinal parasitic infections are a major health problem worldwide.
In Kenya intestinal parasitic infections are highly prevalent especially in
prisons due to poor and/or inadequate infrastructure. The aim of this study was
to establish the risk factors associated with intestinal parasites infection
among inmates of Kisii prison, Kisii county, Kenya. METHODS: Fresh stool samples
of 384 inmates in Kisii prison aged 20 years and above, were screened for
intestinal parasitic infections between February and August 2015. Stool samples
were processed using direct fecal smear and formol-ether sedimentation techniques
for confirmation then they were examined microscopically. Multiple logistic
regression analysis was used to establish the relationship of various factors and
practices with the occurrence of intestinal parasites. The differences were
considered statistically significant at P < 0.05. RESULTS AND DISCUSSION: Of the
384 inmates screened, 95 (24.7 %) were infected with one or more intestinal
parasites. Of the positive inmates, 58 (15.1 %) were infected with one species of
protozoa while 24 (5.2 %) were infected with at least one species of helminthes
and 13 (3.5 %) had mixed infections of species of intestinal parasites. Washing
of hands before meals and after visiting toilets significantly reduced risk of
infections (P < 0.05). The level of education was inversely related to the risk
of intestinal parasites infection where by inmates at post primary education were
least infected with intestinal parasites infection as compared to unschooled
inmates (P < 0.05). Wearing of shoes was seen to significantly reduce parasitic
infections (P <= 0.05). Duties assigned to inmates did not significantly
determine the risk of intestinal parasitic infection (P > 0.05). Male inmates had
significantly more intestinal parasites infections 57 (21.8 %) compared to
females 28 (8.1 %) (P < 0.05). Inmates within ages 20-29 years were more infected
(11.3 %) compared to the age group of >60 years (0.6 %) (P < 0.05). There was no
statistical significant difference between the number of infections among the
length of the jail terms (P < 0.05). CONCLUSIONS: Prevalence of intestinal
parasites was high among inmates in the study area than the general population.
Practices like wearing of shoes, washing of hands before meals after visiting a
toilet and level of education affect the spread of the infections.
PMID- 27484084
TI - ClpP-deletion impairs the virulence of Legionella pneumophila and the optimal
translocation of effector proteins.
AB - BACKGROUND: The opportunistic bacterial pathogen Legionella pneumophila uses
substrate effectors of Dot/Icm type IVB secretion system (T4BSS) to accomplish
survival and replication in amoebae cells and mammalian alveolar macrophages.
During the conversion between its highly resistant, infectious dormant form and
vigorously growing, uninfectious replicative form, L. pneumophila utilizes a
complicated regulatory network in which proteolysis may play a significant role.
As a highly conserved core protease, ClpP is involved in various cellular
processes as well as virulence in bacteria, and has been proved to be required
for the expression of transmission traits and cell division of L. pneumophila.
RESULTS: The clpP-deficient L. pneumophila strain failed to replicate and was
digested in the first 3 h post-infection in mammalian cells J774A.1. Further
investigation demonstrates that the clpP deficient mutant strain was unable to
escape the endosome-lysosomal pathway in host cells. We also found that the clpP
deficient mutant strain still expresses T4BSS components, induces contact
dependent cytotoxicity and translocate effector proteins RalF and LegK2,
indicating that its T4BSS was overall functional. Interestingly, we further found
that the translocation of several effector proteins is significantly reduced
without ClpP. CONCLUSIONS: The data indicate that ClpP plays an important role in
regulating the virulence and effector translocation of Legionella pneumophila.
PMID- 27484086
TI - Risk factors and spatial distribution of extended spectrum beta-lactamase
producing- Escherichia coli at retail poultry meat markets in Malaysia: a cross
sectional study.
AB - BACKGROUND: The significant role of retail poultry meat as an important exposure
pathway for the acquisition and transmission of extended spectrum beta-lactamase
producing Escherichia coli (ESBL-EC) into the human population warrants
understanding concerning those operational practices associated with
dissemination of ESBL-EC in poultry meat retailing. Hence, the objective of this
study was to determine the prevalence, spatial distribution and potential risk
factors associated with the dissemination of ESBL-EC in poultry meat retail at
wet-markets in Selangor, Malaysia. METHODS: Poultry meat (breast, wing, thigh,
and keel) as well as the contact surfaces of weighing scales and cutting boards
were sampled to detect ESBL-EC by using culture and disk combination methods and
polymerase chain reaction assays. Besides, questionnaire was used to obtain data
and information pertaining to those operational practices that may possibly
explain the occurrence of ESBL-EC. The data were analysed using logistic
regression analysis at 95 % CI. RESULTS: The overall prevalence of ESBL-EC was
48.8 % (95 % CI, 42 - 55 %). Among the risk factors that were explored, type of
countertop, sanitation of the stall environment, source of cleaning water, and
type of cutting board were found to be significantly associated with the presence
of ESBL-EC. CONCLUSIONS: Thus, in order to prevent or reduce the presence of ESBL
EC and other contaminants at the retail-outlet, there is a need to design a
process control system based on the current prevailing practices in order to
reduce cross contamination, as well as to improve food safety and consumer
health.
PMID- 27484087
TI - Appraisal of clinical practice guidelines on community-acquired pneumonia in
children with AGREE II instrument.
AB - BACKGROUND: Community-acquired pneumonia (CAP) remains a major cause of morbidity
and mortality worldwide among children. The growing number of guidelines have
been accompanied with a growing concern about variance and conflicts among
guideline recommendations. There is a need to critically appraise clinical
practice guidelines (CPGs) in order to ensure safe and effective practices.
METHODS: A literature search was systematically conducted in English and Chinese
major academic databases (from January 2000 to March 2015). CPGs related to CAP
in children were evaluated by four independent assessors, according to AGREE II
instruments. Standardized domain scores were calculated for each guideline. Inter
rater reliability was assessed by intraclass correlation coefficient. The
software used for analysis was SPSS 17.0. RESULTS: A total of 10 guidelines met
the inclusion criteria and were appraised. Scope and purpose (69.03 %) and
clarity of presentation (83.33 %) achieved relative high scores, while the scores
of the other four domains were low: stakeholder involvement (42.78 %), rigour of
development (44.95 %), applicability (37.60 %), and editorial independence (23.74
%). 3 guidelines were strongly recommended as a result of the overall scores were
greater than 60 %. CONCLUSION: The qualities of CPGs for CAP in children were
generally acceptable with several flaws. Stakeholder involvement, rigour of
development, applicability and editorial independence should be considered and
well described in the future development of CPGs.
PMID- 27484088
TI - The efficacy of sound regulations on the listening levels of pop concerts.
AB - This analysis of new and previously collected data was done to validate the
efficacy of recommendations for limits regarding sound exposure levels at live
pop concerts. After the World Health Organization (WHO) recommended limiting the
sound levels at such concerts to avoid noise induced hearing damage among the
audience, the actual levels at concerts where these recommendations are observed,
have stabilized around 100 dBA. This is a level that is considered acceptable by
WHO. At concerts where there are no limitations, however, the sound levels in the
audience area are still increasing far beyond safe limits and thus the exposure
may represent a serious threat to people's hearing.
PMID- 27484089
TI - The success of the Uttarakhand Cluster: a case study of organisational change
towards disability inclusive development.
AB - BACKGROUND: Persons with disability are often marginalised and excluded from
international development efforts. This case study reviews the success of
Uttarakhand Cluster of development NGOs in changing organisational behaviour
towards being disability inclusive in their development (DID) activities.
METHODS: A triangulation of qualitative research methods was used, including key
informant interviews, focus group discussions and review of textual data.
RESULTS: The results synthesise data into Kotter's framework for organisational
change, explaining the different stages of change experienced by the Cluster as
it moved towards DID. Development of a disability mission, sharing of capacity
and resources, and presence of disability champions were key in the
organisations' transition towards DID. CONCLUSION: This case study demonstrates
that the Cluster, a low - cost network, was able to drive organisational change
and promote DID.
PMID- 27484090
TI - Factor structure and psychometric properties of Chinese version of Beck Anxiety
Inventory in Chinese doctors.
AB - This study analyses the factor structure and psychometric properties of the
Chinese version of Beck Anxiety Inventory on Chinese doctors. Participants
include 762 doctors sampled in 18 public hospitals in three cities in Eastern
China. Exploratory factor analysis is employed to identify the potential factor
structure of the inventory. Confirmatory factor analysis is referred to for model
fit. The results indicate that the Chinese version of Beck Anxiety Inventory has
satisfactory reliability and validity, but its factor structure is unstable and
has great differences compared with international versions. Naming the four
extracted factors is difficult. In general, the Chinese version of Beck Anxiety
Inventory is appropriate for Chinese doctors and can be used as a good screener
to detect the anxiety of Chinese doctors.
PMID- 27484091
TI - A closer look at school bonding among African American adolescents in low-income
communities: A latent class analysis.
AB - Positive school bonding is a significant precursor to students' school success.
However, African American youth report lower school success compared with their
White counterparts. This study examined correlates of school bonding among 633
African American youth who were recruited from community settings in Chicago.
Major findings indicated that negative peer norms, exposure to community
violence, and poor mental health were negatively correlated with school bonding,
while parental monitoring, positive self-regard, and future orientation were
correlated with higher school motivation. Students classified as having high or
moderate school bonding were more likely to live with both parents, experience
higher levels of parental monitoring, and exhibit positive self-regard.
Implications are discussed in view of these findings.
PMID- 27484092
TI - Resilience and hope during advanced disease: a pilot study with metastatic
colorectal cancer patients.
AB - BACKGROUND: The balance between hope-hopelessness plays an important role in the
way terminally ill patients report quality of life, and personal resilience may
be related to hope at the end of life. The objective of this study was to explore
associations between personal resilience, hope, and other possible predictors of
hope in advanced cancer patients. METHODS: A cross-sectional pilot study was
carried out with metastatic colorectal cancer patients in a tertiary hospital.
The patients answered the Connor-Davidson Resilience Scale, Herth Hope Index,
Barthel Index, an instrument addressing family and social support, visual-numeric
scales for pain and suffering, a two-item screening for depression, socio
demographic and socio-economic information about the family. RESULTS: Forty-four
patients were interviewed (mean age 56 years; range 29-86). A strong correlation
was noted between resilience and hope (0.63; p < 0.05). No correlation was found
between hope and independence for activities of daily living, support from family
and community, and pain and suffering levels. Of the 44 patients, 20 presented
with depressive symptoms. These depressive patients had lower resilience (p =
0.005) and hope (p = 0.003), and higher scores of suffering (p < 0.001). The
association between resilience and hope kept stable after adjusting for age,
gender, and presence of depression (p < 0.001). CONCLUSION: Given that resilience
is a dynamic, changeable path that can improve hope, resilience-fostering
interventions should be most valued in palliative care settings and should be
commenced as soon as possible with cancer patients. Patients with advanced stages
of non-malignant conditions would also probably benefit from such interventions.
PMID- 27484093
TI - The clinical significance of forkhead box protein A1 and its role in colorectal
cancer.
AB - Forkhead box protein A1 (FOXA1) is a transcription factor; recent studies have
reported that FOXA1 has an oncogenic or tumor suppressive role in human
malignancies, and its expression is associated with the prognosis of patients
with cancer. However, further studies are required to determine the clinical
significance of FOXA1 and its role in colorectal cancer (CRC). In the present
study, FOXA1 expression was detected in 90 samples of CRC tissues and matched
noncancerous tissues using immunohistochemistry. In these cases, FOXA1 expression
was detected in 57.8% (52/90) of the CRC samples, whereas only 37.8% (34/90) of
the noncancerous specimens exhibited a positive FOXA1 signal. In addition, the
present study demonstrated that the mRNA expression levels of FOXA1 were
significantly increased in CRC tissues compared with in matched tumor-adjacent
tissues. Furthermore, the positive expression of FOXA1 was associated with poor
clinicopathological characteristics of CRC, including poor tumor differentiation,
large tumor size, lymph node metastases and advanced tumor-node-metastasis tumor
stage. Notably, patients with CRC with positive FOXA1 expression exhibited a
significantly reduced 5-year survival rate compared with those with negative
FOXA1 expression. Multivariate Cox regression analysis revealed that FOXA1
expression was an independent prognostic indicator for patients with CRC. In
addition, FOXA1 knockdown evidently inhibited cell proliferation and induced
apoptosis in SW480 and HCT116 CRC cells. Notably, FOXA1 knockdown also
prominently reduced the expression of yes-associated protein (YAP) in SW480 and
HCT116 cells. In conclusion, the results of the present study indicated that
FOXA1 may be considered a potential prognostic marker, and may promote tumor
growth of CRC by upregulating YAP expression.
PMID- 27484094
TI - Atorvastatin ameliorates endothelium-specific insulin resistance induced by high
glucose combined with high insulin.
AB - The aim of the present study was to establish an endothelial cell model of
endothelium-specific insulin resistance to evaluate the effect of atorvastatin on
insulin resistance-associated endothelial dysfunction and to identify the
potential pathway responsible for its action. Cultured human umbilical vein
endothelial cells (HUVECs) were pretreated with different concentrations of
glucose with, or without, 10-5 M insulin for 24 h, following which the cells were
treated with atorvastatin. The tyrosine phosphorylation of insulin receptor (IR)
and insulin receptor substrate-1 (IRS-1), the production of nitric oxide (NO),
the activity and phosphorylation level of endothelial NO synthase (eNOS) on
serine1177, and the mRNA levels of endothelin-1 (ET-1) were assessed during the
experimental procedure. Treatment of the HUVECs with 30 mM glucose and 10-5 M
insulin for 24 h impaired insulin signaling, with reductions in the tyrosine
phosphorylation of IR and protein expression of IRS-1 by almost 75 and 65%,
respectively. This, in turn, decreased the activity and phosphorylation of eNOS
on serine1177, and reduced the production of NO by almost 80%. By contrast, the
mRNA levels of ET-1 were upregulated. All these changes were ameliorated by
atorvastatin. Taken together, these results demonstrated that high concentrations
of glucose and insulin impaired insulin signaling leading to endothelial
dysfunction, and that atorvastatin ameliorated these changes, acting primarily
through the phosphatidylinositol 3-kinase/Akt/eNOS signaling pathway.
PMID- 27484096
TI - Reduced Mucosa-associated Butyricicoccus Activity in Patients with Ulcerative
Colitis Correlates with Aberrant Claudin-1 Expression.
AB - BACKGROUND AND AIMS: Butyricicoccus is a butyrate-producing clostridial cluster
IV genus whose numbers are reduced in the stool of ulcerative colitis [UC]
patients. Conditioned medium of Butyricicoccus [B.] pullicaecorum prevents tumour
necrosis factor alpha [TNFalpha]-induced increase in epithelial permeability in
vitro. Since butyrate influences intestinal barrier integrity, we further
investigated the relationship between the abundance of mucosa-associated
Butyricicoccus and the expression of butyrate-regulated tight junction [TJ]
genes. METHODS: Tight junction protein 1 [TJP1], occludin [OCLN], claudin-1
[CLDN1], and Butyricicoccus 16S rRNA expression was analysed in a collection of
colonic biopsies of healthy controls and UC patients with active disease. The
effect of butyrate and B. pullicaecorum conditioned medium on TJ gene expression
was investigated in TNFalpha-stimulated Caco-2 monolayers and inflamed mucosal
biopsies of UC patients. RESULTS: TJP1 expression was significantly decreased in
inflamed UC mucosa, whereas CLDN1 mRNA levels were increased. OCLN did not differ
significantly between the groups. Mucosa-associated Butyricicoccus 16S rRNA
transcripts were reduced in active UC patients compared with healthy controls.
Interestingly, Butyricicoccus activity negatively correlated with CLDN1
expression. Butyrate reversed the inflammation-induced increase of CLDN1 protein
levels, and stimulation of inflamed UC biopsies with B. pullicaecorum conditioned
medium normalized CLDN1 mRNA levels. CONCLUSIONS: Butyricicoccus is a mucosa
associated bacterial genus under-represented in colonic mucosa of patients with
active UC, whose activity inversely correlates with CLDN1 expression. Butyrate
and B. pullicaecorum conditioned medium reduce CLDN1 expression, supporting its
use as a pharmabiotic preserving epithelial TJ integrity.
PMID- 27484095
TI - Integrated molecular pathway analysis informs a synergistic combination therapy
targeting PTEN/PI3K and EGFR pathways for basal-like breast cancer.
AB - BACKGROUND: The basal-like breast cancer (BLBC) subtype is characterized by
positive staining for basal mammary epithelial cytokeratin markers, lack of
hormone receptor and HER2 expression, and poor prognosis with currently no
approved molecularly-targeted therapies. The oncogenic signaling pathways driving
basal-like tumorigenesis are not fully elucidated. METHODS: One hundred sixteen
unselected breast tumors were subjected to integrated analysis of
phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations by
immunohistochemistry, mutation analysis, and gene expression profiling. Incidence
and relationships between molecular biomarkers were characterized. Findings for
select biomarkers were validated in an independent series. Synergistic cell
killing in vitro and in vivo tumor therapy was investigated in breast cancer cell
lines and mouse xenograft models, respectively. RESULTS: Sixty-four % of cases
had an oncogenic alteration to PIK3CA, PTEN, or INPP4B; when including upstream
kinases HER2 and EGFR, 75 % of cases had one or more aberration including 97 % of
estrogen receptor (ER)-negative tumors. PTEN-loss was significantly associated to
stathmin and EGFR overexpression, positivity for the BLBC markers cytokeratin
5/14, and the BLBC molecular subtype by gene expression profiling, informing a
potential therapeutic combination targeting these pathways in BLBC. Combination
treatment of BLBC cell lines with the EGFR-inhibitor gefitinib plus the PI3K
pathway inhibitor LY294002 was synergistic, and correspondingly, in an in vivo
BLBC xenograft mouse model, gefitinib plus PI3K-inhibitor PWT-458 was more
effective than either monotherapy and caused tumor regression. CONCLUSIONS: Our
study emphasizes the importance of PI3K/PTEN pathway activity in ER-negative and
basal-like breast cancer and supports the future clinical evaluation of combining
EGFR and PI3K pathway inhibitors for the treatment of BLBC.
PMID- 27484097
TI - Phase 1 Clinical Study of siRNA Targeting Carbohydrate Sulphotransferase 15 in
Crohn's Disease Patients with Active Mucosal Lesions.
AB - BACKGROUND AND AIMS: Carbohydrate sulphotransferase 15 [CHST15] is a specific
enzyme biosynthesizing chondroitin sulphate E that binds various pathogenic
mediators and is known to create local fibrotic lesions. We evaluated the safety
of STNM01, a synthetic double-stranded RNA oligonucleotide directed against
CHST15, in Crohn's disease [CD] patients whose mucosal lesions were refractory to
conventional therapy. METHODS: This was a randomized, double-blind, placebo
controlled, concentration-escalation study of STNM01 by a single-dose endoscopic
submucosal injection in 18 CD patients. Cohorts of increasing concentration of
STNM01 were enrolled sequentially as 2.5nM [n = 3], 25nM [n = 3], and 250nM [n =
3] were applied. A cohort of placebo [n = 3] was included in each concentration.
Safety was monitored for 30 days. Pharmacokinetics was monitored for 24h. The
changes from baseline in the segmental Simple Endoscopic Score for CD [SES-CD] as
well as the histological fibrosis score were evaluated. RESULTS: STNM01 was well
tolerated and showed no drug-related adverse effects in any cohort of treated
patients. There were no detectable plasma concentrations of STNM01 at all
measured time points in all treatment groups. Seven of nine subjects who received
STNM01 showed reduction in segmental SES-CD at Day 30, when compared with those
who received placebo. Histological analyses of biopsy specimens revealed that
STNM01 reduced the extent of fibrosis. CONCLUSION: Local application of STNM01 is
safe and well tolerated in CD patients with active mucosal lesions.
PMID- 27484098
TI - A case of IgG4-related hepatic inflammatory pseudotumor replaced by an abscess
after steroid treatment.
AB - BACKGROUND: Hepatic inflammatory pseudotumor (IPT) is a rare disease which often
mimics a malignant tumor and is therefore often misdiagnosed and surgically
resected. Recently, a concept of IgG4-related diseases (IgG4-RD) has been
proposed that is becoming widely recognized and includes IgG4-related hepatic
IPT. Corticosteroids are widely accepted as the standard treatment. CASE
PRESENTATION: A 72-year-old Japanese man, who had been followed for ten years
after surgery and chemotherapy for treatment of hilar and lower bile duct
cancers, developed intermittent fever and abdominal pain and visited this
hospital. Blood examinations revealed an inflammatory reaction, worsened glucose
intolerance, and an increased level of serum IgG4 (137 mg/dL). Computed
tomography (CT) revealed a 5 cm-sized mass in hepatic segment 7. Because of his
cancer history, not only was a benign mass suspected, but there was also the
possibility of a recurrent biliary malignancy. Liver biopsy was performed and the
histology met the criteria for IgG4-related IPT. Corticosteroid therapy was
initiated and his symptoms quickly resolved. However, two months later, a repeat
CT demonstrated that the hepatic mass had been replaced by an abscess. The
abscess was initially refractory, despite tapering corticosteroid treatment,
controlling diabetes by intensive insulin therapy, administration of antibiotics,
and percutaneous abscess drainage. Finally, after six months, the condition
resolved. CONCLUSION: The diagnosis of hepatic IPT is sometimes difficult. To
differentiate it from a malignant tumor, histological examination is necessary.
Although corticosteroids are recognized as the standard therapy, unexpected and
critical complications can develop in cases of IgG4-related hepatic IPT.
PMID- 27484099
TI - Contents of Ag and other metals in food-contact plastics with nanosilver or Ag
ion and their migration into food simulants.
AB - Six nanosilver-labelled products and five silver ion (Ag(+))-labelled products
were investigated to measure the migration of Ag from food-contact plastics,
including nanosilver into various food simulants. The products were obtained in
Japanese markets in 2012. Zinc (Zn), another major antimicrobial agent, and three
harmful metals, cadmium (Cd), lead (Pb) and arsenic (As), were also examined. Ag
and Zn were detected in all six nanosilver products at concentrations of 21-200
and 8.4-140 mg kg(-1), respectively. These metals were also detected in all five
Ag(+) products at the same level as nanosilver products. Cd, Pb and As were not
detected in any sample. Migrations of Ag and Zn were highest in 4% acetic acid,
but also observed in water and 20% ethanol. Big differences were not observed in
the migration ratio between nanosilver products and Ag(+) products. The
ultrafiltration experiments suggested that the Ag that migrated from nanosilver
products into 4% acetic acid was in its ionic form, while that into water and 20%
ethanol was in its nanoparticle form.
PMID- 27484100
TI - CT in ovarian cancer staging: how to review and report with emphasis on abdominal
and pelvic disease for surgical planning.
AB - CT of the abdomen and pelvis is the first line imaging modality for staging,
selecting treatment options and assessing disease response in ovarian cancer. The
staging CT provides disease distribution, disease burden and is the imaging
surrogate for surgico-pathological FIGO staging. Optimal cyto-reductive surgery
offers patients' the best chance for disease control or cure, but sub-optimal
resection confers no advantage over chemotherapy and adversely increases the risk
of post surgical complications. Although there is extensive literature comparing
performance of CT against laparoscopy and surgery, for the staging abdominal and
pelvic CT, there are currently no accepted guidelines for interpretation or
routinely used minimum data set templates for reporting these complex CT scans
often with extensive radiological findings. This review provides a systematic
approach for identifying the important radiological findings and highlighting
important sites of disease within the abdomen and pelvis, which may alter or
preclude surgery at presentation or after adjuvant chemotherapy. The distribution
of sites and volume of disease can be used to categorize patients as suitable,
probably suitable or not suitable for optimal cyto-reductive surgery. This
categorization can potentially assist oncological surgeons and oncologists as a
semi objective assessment tool useful for selecting patient treatment,
streamlining multi disciplinary discussion and improving the reproducibility and
correlation of CT with surgical findings. The review also highlights sites of
disease and complications of ovarian cancer which should be included as part of
the radiological report as these may require additional surgical input from non
gynaecological surgeons or influence treatment selection.
PMID- 27484101
TI - Creating Possible ... Aesthetically Engaging Life Amid Reminders of Our
Mortality.
PMID- 27484102
TI - The impact of uphill cycling and bicycle suspension on downhill performance
during cross-country mountain biking.
AB - Non-propulsive work demand has been linked to reduced energetic economy of cross
country mountain biking. The purpose of this study was to determine mechanical,
physiological and performance differences and observe economy while riding a
downhill section of a cross-country course prior to and following the metabolic
"load" of a climb at race pace under two conditions (hardtail and full
suspension) expected to alter vibration damping mechanics. Participants completed
1 lap of the track incorporating the same downhill section twice, under two
conditions (hardtail and full suspension). Performance was determined by time to
complete overall lap and specific terrain sections. Power, cadence, heart rate
and oxygen consumption were sampled and logged every second while triaxial
accelerometers recorded accelerations (128 Hz) to quantify vibration. No
differences between performance times (P = 0.65) or power outputs (P = 0.61) were
observed while physiological demand of loaded downhill riding was significantly
greater (P < 0.0001) than unloaded. Full suspension decreased total vibrations
experienced (P < 0.01) but had no effect on performance (P = 0.97) or
physiological (P > 0.05) measures. This study showed minimal advantage of a full
suspension bike in our trial, with further investigations over a full race
distance warranted.
PMID- 27484103
TI - An integrated approach of network-based systems biology, molecular docking, and
molecular dynamics approach to unravel the role of existing antiviral molecules
against AIDS-associated cancer.
AB - A serious challenge in cancer treatment is to reposition the activity of various
already known drug candidates against cancer. There is a need to rewrite and
systematically analyze the detailed mechanistic aspect of cellular networks to
gain insight into the novel role played by various molecules. Most Human
Immunodeficiency Virus infection-associated cancers are caused by oncogenic
viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS
associated cancers marks the severity of AIDS, there might be possible
interconnections between the targets and mechanism of both the diseases. We have
explored the possibility of certain antiviral compounds to act against major AIDS
associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer
with the help of systems pharmacology approach that includes screening for
targets and molecules through the construction of a series of drug-target and
drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B)
and the target "HRAS" were finally screened with the help of molecular docking
and molecular dynamics simulation. The results provide novel antiviral molecules
against HRAS target to treat AIDS defining cancers and an insight for
understanding the pharmacological, therapeutic aspects of similar unexplored
molecules against various cancers.
PMID- 27484104
TI - NBR1-dependent selective autophagy is required for efficient cell-matrix adhesion
site disassembly.
AB - Macroautophagy/autophagy has classically been recognized for its vital role in
supporting cellular survival during various stresses. However, emerging work has
demonstrated that selective autophagy has an impact on diverse cell biological
processes by mediating the degradation of various cellular contents during normal
cellular homeostasis. We recently established that selective autophagy supports
cell migration by promoting the turnover of integrin-based cell-matrix adhesion
sites, or focal adhesions (FAs). The autophagy cargo receptor NBR1 acts as a
critical mediator of this pathway by promoting targeting of autophagosomes to
FAs, leading to their disassembly via the sequestration of FA proteins. Our
results demonstrate FAs as a new cellular target for selective autophagy.
PMID- 27484105
TI - Exaggerated phosphorylation of brain tau protein in CRH KO mice exposed to
repeated immobilization stress.
AB - Neuroendocrine and behavioral stress responses are orchestrated by corticotropin
releasing hormone (CRH) and norepinephrine (NE) synthesizing neurons. Recent
findings indicate that stress may promote development of neurofibrillary
pathology in Alzheimer's disease. Therefore, we investigated relationships among
stress, tau protein phosphorylation, and brain NE using wild-type (WT) and CRH
knockout (CRH KO) mice. We assessed expression of phosphorylated tau (p-tau) at
the PHF-1 epitope and NE concentrations in the locus coeruleus (LC), A1/C1 and
A2/C2 catecholaminergic cell groups, hippocampus, amygdala, nucleus basalis
magnocellularis, and frontal cortex of unstressed, singly stressed or repeatedly
stressed mice. Moreover, gene expression and protein levels of tyrosine
hydroxylase (TH) and CRH receptor mRNA were determined in the LC. Plasma
corticosterone levels were also measured. Exposure to a single stress increases
tau phosphorylation throughout the brain in WT mice when compared to singly
stressed CRH KO animals. In contrast, repeatedly stressed CRH KO mice showed
exaggerated tau phosphorylation relative to WT controls. We also observed
differences in extent of tau phosphorylation between investigated structures,
e.g. the LC and hippocampus. Moreover, CRH deficiency leads to different
responses to stress in gene expression of TH, NE concentrations, CRH receptor
mRNA, and plasma corticosterone levels. Our data indicate that CRH effects on tau
phosphorylation are dependent on whether stress is single or repeated, and
differs between brain regions. Our findings indicate that CRH attenuates
mechanisms responsible for development of stress-induced tau neuropathology,
particularly in conditions of chronic stress. However, the involvement of central
catecholaminergic neurons in these mechanisms remains unclear and is in need of
further investigation.
PMID- 27484106
TI - Static and Functional Balance in Individuals With COPD: Comparison With Healthy
Controls and Differences According to Sex and Disease Severity.
AB - BACKGROUND: Studies have shown that individuals with COPD have impaired body
balance, probably caused by the disease's multisystemic manifestations plus age
related decline in balance, potentially increasing the risk of falling and its
consequences. However, little is known about the profile of individuals with COPD
who present balance impairments, especially related to sex and disease severity
stages. The aim of this work was to compare static and functional balance between
subjects with COPD and healthy controls and to check possible differences
according to sex and degrees of disease severity. METHODS: Forty-seven subjects
with COPD and 25 healthy controls were included in this study. Their static
balance was assessed in one-legged stance using a force platform and functional
balance with the Timed Up and Go test. Additionally, participants performed
spirometry, the 6-min walk test and isometric quadriceps maximal voluntary
contraction assessment. Disease severity was classified according to the Global
Initiative for Obstructive Lung Disease stages and BODE (body mass index, air
flow obstruction, dyspnea, and exercise capacity) scores. RESULTS: In comparison
with healthy controls, subjects with COPD had worse static (center of pressure
displacement area: 9.3 +/- 1.9 cm2 vs 11.6 +/- 4.0 cm2, respectively, P = .01)
and functional balance (Timed Up and Go test: 8.5 +/- 1.3 s vs 10.3 +/- 1.8 s,
respectively, P < .001). In the COPD group, men performed better in the Timed Up
and Go test than women (9.8 +/- 1.2 s vs 10.9 +/- 2.2 s, respectively, P = .03),
whereas women presented a better static balance in comparison with men for all
parameters related to center of pressure (P < .005 for all). Disease severity did
not affect any balance results. CONCLUSIONS: Individuals with COPD had worse
static and functional balance in comparison with healthy controls. Sex can
mediate these results, depending on the type of balance evaluation (force
platform or functional test). Balance performance was similar among the groups
classified according to disease severity.
PMID- 27484107
TI - Impulse Oscillometry and Spirometry Small-Airway Parameters in Mild to Moderate
Bronchiectasis.
AB - BACKGROUND: Both impulse oscillometry and spirometry can reflect small-airway
disorders. The objective of this work was to investigate the diagnostic value of
impulse oscillometry and spirometry small-airway parameters and their correlation
with radiology, disease severity, and sputum bacteriology in mild to moderate
bronchiectasis (bronchiectasis severity index <9) and to validate these findings
in sensitivity analyses (mild bronchiectasis). METHODS: We recruited 94 subjects
with mild to moderate bronchiectasis and 26 healthy subjects. The diagnostic
value of small-airway parameters was compared using the receiver operating
characteristic curve. Chest high-resolution computed tomography (HRCT), impulse
oscillometry measurement, spirometry, and sputum culture were performed.
Correlation between small-airway parameters and clinical indices was determined,
adjusting for age, sex, body mass index, and smoking history. Sensitivity
analyses were repeated when excluding subjects with bronchiectasis severity index
>=9 or HRCT score >=13. RESULTS: Impulse oscillometry and spirometry small-airway
parameters could discriminate mild to moderate bronchiectasis from healthy
subjects and correlated significantly with HRCT score and the number of
bronchiectatic lobes and the bronchiectasis severity index (all P < .01). Small
airway parameters were more aberrant in subjects with dyshomogeneity and cystic
bronchiectasis but were independent of Pseudomonas aeruginosa isolation or the
location of predominant bronchiectatic lobes. Spirometry, but not impulse
oscillometry, small-airway parameters differed statistically between subjects
with isolated peripheral-airway bronchiectasis and those with peripheral plus
central-airway bronchiectasis (all P < .01). Subgroup analyses yielded similar
findings, except for the lack of correlation between small-airway parameters and
clinical parameters in subjects with HRCT score <=6. CONCLUSIONS: Impulse
oscillometry and spirometry small-airway parameters have similar diagnostic value
in reflecting peripheral-airway disorders and correlate with the HRCT scores, the
bronchiectasis severity index, and the number of bronchiectatic lobes in mild to
moderate bronchiectasis. Assessment of small-airway parameters should be
incorporated in future lung function investigations in bronchiectasis.
PMID- 27484108
TI - Rationale and Description of Right Ventricle-Protective Ventilation in ARDS.
AB - Pulmonary vascular dysfunction is associated with ARDS and leads to increased
right-ventricular afterload and eventually right-ventricular failure, also called
acute cor pulmonale. Interest in acute cor pulmonale and its negative impact on
outcome in patients with ARDS has grown in recent years. Right-ventricular
function in these patients should be closely monitored, and this is helped by the
widespread use of echocardiography in intensive care units. Because mechanical
ventilation may worsen right-ventricular failure, the interaction between the
lungs and the right ventricle appears to be a key factor in the ventilation
strategy. In this review, a rationale for a right ventricle-protective
ventilation approach is provided, and such a strategy is described, including the
reduction of lung stress (ie, the limitation of plateau pressure and driving
pressure), the reduction of PaCO2 , and the improvement of oxygenation. Prone
positioning seems to be a crucial part of this strategy by protecting both the
lungs and the right ventricle, resulting in increased survival of patients with
ARDS. Further studies are required to validate the positive impact on prognosis
of right ventricle-protective mechanical ventilation.
PMID- 27484109
TI - Modalities and Complications Associated With the Use of High-Flow Nasal Cannula:
Experience in a Pediatric ICU.
AB - BACKGROUND: High-flow nasal cannula (HFNC) therapy is increasingly used in
pediatric ICUs as an intermediate level of support between conventional oxygen
delivery and noninvasive ventilation (NIV). The safety of HFNC has seldom been
studied, and some cases of barotrauma have been reported. This retrospective
study aims to describe HFNC use in a tertiary care pediatric ICU, with a focus on
the complications associated with this therapy. METHODS: Between January 2013 and
January 2014, all children <18 y old treated with HFNC in the pediatric ICU were
included. Demographic data, HFNC settings, chest radiograph reports, and blood
gas values were gathered from the electronic medical records. Episodes of
pneumothorax, pneumomediastinum, and significant epistaxis were noted.
Pneumothorax was distinguished from chest tube-related air leak (frequent after
cardiac surgery), which was defined as a small pneumothorax with no clinical
impact that resolved spontaneously after chest tube removal. RESULTS: During the
1-y study period, there were 177 HFNC episodes, involving 145 subjects with a
median (interquartile range) age of 8 (2-28) months. HFNC was used as primary
support in 31% of episodes, after extubation in 36% and after NIV in 18%. HFNC
was administered exclusively for nitric oxide delivery in 16% of episodes. Two
children (1%) developed new pneumothoraces that required chest tube insertion,
whereas 5 (3%) chest tube-related air leaks were noted. One (0.6%) episode of
significant epistaxis was noted. Among 6 preexisting pneumothoraces, none
worsened under HFNC. Failure of HFNC occurred in 32 episodes, requiring
transition to NIV in 28 cases and endotracheal intubation in 5 cases.
CONCLUSIONS: Support with HFNC following a clinical protocol in pediatric ICUs
was associated with a relatively low rate of complications. Since HFNC use is
increasing, further evidence is needed to confirm its efficacy and safety.
PMID- 27484110
TI - Silica Exposure and Effect on Peak Expiratory Flow: Slate Pencil Workers' Study.
AB - BACKGROUND: Peak expiratory flow (PEF) is a spirometric test that detects
obstructive changes in the respiratory tract; has good correlation with the FEV1;
and is much less expensive, simpler, and easier to perform under field conditions
than FEV1. Chronic silicosis is also known to have obstructive features in
advanced stages. Thus, this study was performed to assess the effect of silica
exposure on PEF and the factors related to it. METHODS: The present study was
carried out among 193 slate pencil cutting workers of Multanpura village of
Madhya Pradesh, India. An interview technique was used to record demographic
characteristics and occupational history on a predesigned form, which included a
questionnaire regarding occupational history and silica-related respiratory
morbidities. This was followed by a complete medical examination and measurement
of PEF using a spirometer. RESULTS: The mean age was 43.35 +/- 11.31 y, and the
mean duration of exposure was 18.72 +/- 9.33 y. In the present study, PEF was
found to be significantly reduced in those age >=40 y, those who were female,
those having duration of exposure >10 y, and those having respiratory morbidity,
whereas the reduction in PEF was statistically nonsignificant for smokers.
CONCLUSIONS: Higher age, female sex, higher duration of exposure, and respiratory
morbidity were found to be important correlates of PEF.
PMID- 27484111
TI - A neural substrate for object permanence in monkey inferotemporal cortex.
AB - We take it for granted that objects continue to exist after being occluded. This
knowledge - known as object permanence - is present even in childhood, but its
neural basis is not fully understood. Here, we show that monkey inferior temporal
(IT) neurons carry potential signals of object permanence even in animals that
received no explicit behavioral training. We compared two conditions with
identical visual stimulation: the same object emerged from behind an occluder as
expected following its occlusion, or unexpectedly after occlusion of a different
object. Some neurons produced a larger (surprise) signal when the object emerged
unexpectedly, whereas other neurons produced a larger (match) signal when the
object reappeared as expected. Neurons carrying match signals also reinstated
selective delay period activity just before the object emerged. Thus, signals
related to object permanence are present in IT neurons and may arise through an
interplay of memory and match computations.
PMID- 27484112
TI - The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During
Endotoxemia.
AB - Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)
induced endotoxic shock in animals as well as in critically ill patients. Here we
studied the role of the thyroid hormone receptors (TRs) in activation of STAT3,
NF-kappaB and ERK, which play a key role in the response to inflammatory
cytokines during sepsis. TR knockout mice showed down-regulation of hepatic
inflammatory mediators, including interleukin 6 (IL-6) in response to LPS.
Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act
as endogenous repressors of these pathways. Furthermore, hyperthyroidism
increased cytokine production and mortality in response to LPS, despite
decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly
repress the response of the cells to inflammatory mediators. Indeed, we found
that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and
hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone
strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3
recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs
are potent regulators of inflammatory responses and immune homeostasis during
sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism
for preventing deleterious effects of excessive hormone signaling during
infections.
PMID- 27484113
TI - High intensity focused ultrasound in the treatment of breast fibroadenomata:
results of the HIFU-F trial.
AB - OBJECTIVES: Breast fibroadenomata (FAD) are the most common breast lumps in
women. High intensity focused ultrasound (HIFU) is a non-invasive ablative
technique that can be used to treat FAD but is associated with prolonged
treatment times. In the HIFU-F trial, we evaluated the change in volume over time
with circumferential HIFU treatment of FAD and compared this to no treatment.
METHODS: Patients >=18 years, diagnosed with symptomatic, palpable FAD, visible
on ultrasound (US) were recruited. Twenty patients were treated using US-guided
HIFU under local anaesthesia. Another 20 participants underwent an US 6 months
after diagnosis. Outcome measures included: reduction in treatment time compared
to whole lesion ablation; feasibility to achieve a 50% reduction in volume after
6 months; decrease in volume compared to a control group and reduction in
symptoms. RESULTS: Circumferential ablation reduced the mean treatment time by
37.5% (SD 20.1%) compared to whole lesion ablation. US demonstrated a significant
mean reduction in FAD volume of 43.5% (SD 38.8%; p = 0.016, paired t-test) in the
HIFU group compared to 4.6% (SD 46.0%; p = 0.530) in the control group after 6
months. This mean reduction in FAD volume between the two groups was significant
in favour of the HIFU group (p = 0.002, grouped t-test). Pre-treatment pain
completely resolved in 6 out of 8 patients 6 months post-treatment. CONCLUSION:
Circumferential HIFU ablation of FAD is feasible, with a significant reduction in
pain and volume compared to control participants. It provides a simple, non
invasive, outpatient-based alternative to surgical excision for FAD.
PMID- 27484114
TI - Polydopamine Thin Films as Protein Linker Layer for Sensitive Detection of
Interleukin-6 by Surface Plasmon Enhanced Fluorescence Spectroscopy.
AB - Polydopamine (PDA) thin films are introduced to the surface modification of
biosensor surfaces utilizing surface plasmon enhanced fluorescence spectroscopy
(SPFS) as the linker layer of capture antibody on to the sensor surfaces. The
capture antibody can be directly attached to the sensor surface without using any
coupling agent by functionalizing the gold sensor surface with PDA thin films.
The PDA coating is performed by a single-step preparation process by applying the
dopamine solution on the sensor surface, which requires an extremely short
incubation time (10 min). The real-time in situ measurement of the adsorption
kinetics of the capture antibody onto the PDA-coated sensor surface is studied by
surface plasmon resonance (SPR) spectroscopy. It reveals that the immobilization
of capture antibody immediately occurs after introduction of a solution
containing capture antibody, and the sensor surface is fully covered with the
capture antibody. The sensitive detection of the cytokine marker interleukin-6
(IL-6) is performed by SPFS using a sandwich assay format with fluorescently
labeled detection antibody. The sensor chips functionalized by PDA chemistry
exhibited sensitive sensor responses with low nonspecific adsorption of the
detection antibody onto the sensor surface. The detection limit of IL-6 with the
developed SPFS biosensor is determined to be 2 pg/mL (100 fM), which is within
the range of the diagnostic criteria. Our observation elucidates the remarkable
utility of PDA coatings for chemical modification of the metallic sensor surfaces
by a simple, brief, and inexpensive manner.
PMID- 27484116
TI - Peripheral KATP activation inhibits pain sensitization induced by skin/muscle
incision and retraction via the nuclear factor-kappaB/c-Jun N-terminal kinase
signaling pathway.
AB - The aim of the current study was to assess the effect of pinacidil activation of
ATP-sensitive potassium (KATP) channels prior to skin/muscle incision and
retraction (SMIR) surgery on peripheral and central sensitization, and
investigate molecular interferential targets for preventive analgesia. Male
Sprague-Dawley rats were randomly assigned to one of the following five groups:
Control, incision (sham surgery), incision plus retraction (SMIR) group, SMIR
plus pinacidil (pinacidil) group and the SMIR plus pyrrolidine dithiocarbamate
(PDTC) group. The rats in the pinacidil and PDTC groups were intraperitoneally
injected with pinacidil or PDTC, respectively, prior to the SMIR procedure. The
mechanical withdrawal threshold (MWT) was determined. Western blotting was
performed to detect the alterations in the subunits of the KATP channels, Kir6.1
and SUR2, levels of nuclear factor-kappaB (NF-kappaB) in the tissue around the
incision and c-Jun N-terminal kinase (JNK) in the spinal cord. There was a
significant increase observed in the levels of NF-kappaB and JNK following SMIR
surgery compared with the control group, and a significant reduction in MWT and
the levels of Kir6.1 and SUR2. Additionally, intraperitoneal administration of
pinacidil inhibited the reduction in MWT, and Kir6.1 and SUR2 levels. SMIR was
observed to result in increases in the levels of NF-kappaB and JNK. In addition,
in the PDTC group, the alterations in MWT, NF-kappaB, JNK, Kir6.1 and SUR2
resulting from SMIR were blocked. The results of the current study suggest that
the deteriorations in the microenvironment resulting from the SMIR procedure can
induce peripheral and central sensitization, and that the activation of
peripheral KATP by pinacidil prior to SMIR is able to inhibit peripheral and
central sensitization via the NF-kappaB/JNK signaling pathway, thus resulting in
preventive analgesia.
PMID- 27484115
TI - Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone
Formation.
AB - The precipitation of excess biliary cholesterol as solid crystals is a
prerequisite for cholesterol gallstone formation, which occurs due to disturbed
biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of
genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse
and form gallstones. We have previously observed that the levels of osteopontin
(OPN) in bile and gallbladder were reduced in gallstone patients. However, the
role and mechanism for hepatic OPN in cholesterol gallstone formation is
undetermined. In this study, we found that the expression of hepatic OPN was
increased in gallstone patients compared with gallstone-free counterparts. Then,
we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone
formation than wild type mice. Further mechanistic studies revealed that this
protective effect was associated with alterations of bile composition and was
caused by the increased hepatic CYP7A1 expression and the reduced expression of
hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the
expression of hepatic OPN and the expression of these hepatic genes were
validated in gallstone patients. Taken together, our findings reveal that hepatic
OPN contributes to cholesterol gallstone formation by regulating biliary
metabolism and might be developed as a therapeutic target for gallstone
treatments.
PMID- 27484117
TI - EDITORIAL: Chemodescriptor Based QSARs of Structurally Homogeneous Versus
Heterogeneous Chemical Data Sets: Some Comments on the Congenericity Principle
vis-a-vis Diversity Begets Diversity Principle.
PMID- 27484118
TI - Molecular Dynamics Simulation Reveal the Mechanism of Resistance of Mutant Actins
to Latrunculin A - Insight into Specific Modifications to Design Novel Drugs to
Overcome Resistance.
AB - BACKGROUND: Mutant actins D157E and R183A-D184A are reported to resist the
anticancer drug Latrunculin A (LAT); though identified, the mechanism of
resistance is not clearly understood. OBJECTIVE: To design better molecules that
can overcome the resistance caused by mutations it is important to define precise
pharmacophoric regions in LAT based on the mechanism of resistance on the mutant
actin -LAT interactions. METHODS: To address this we have conducted 20 nano
seconds (ns) simulation of mutant actins - LAT complex and compared it with the
20ns simulation of wild actin - LAT complex. Functions as the binding free
energy, distance between LAT and binding site residues, LAT and actin domains,
dihedral angle analysis, motional correlation were studied of these simulations.
RESULTS: Grounded on these studies, four sites in LAT are identified to be
crucial for modification. Bulkier ring moieties containing nitrogen in place of
the double bonded oxygen in the macrocyclic lactone ring may be considered to
establish interactions with Glu214. The nitrogen in 2-thiazolidinone moiety can
be substituted with a hydrophobic ring to stabilise the interaction with the
Asp157Glu and the oxygen in the cyclohexane of LAT with hydrophilic groups to
strengthen their interaction with Tyr69. The nitrogen of the 2-thiazolidinone
moiety can be replaced with nitrogen containing rings to improve inhibition of
the actin polymerisation. Apart from this chemical groups on the sulphur of 2
thiazolidinone moiety to improve the hydrophobic interaction with actin is also
identified for modification. CONCLUSION: Based on this a combinatorial library of
46 LAT analogs was generated and docked with the wild and mutant actins to
identify potent leads to become anti-actin anticancer drugs.
PMID- 27484119
TI - Biological sex identification in the endangered dusky gopher frog (Lithobates
sevosa): a comparison of body size measurements, secondary sex characteristics,
ultrasound imaging, and urinary hormone analysis methods.
AB - BACKGROUND: Accurate sex identification techniques are important for wildlife
demographic studies and for genetic management of captive breeding colonies.
Various non-invasive methods for identification of biological sex in the weakly
dimorphic endangered dusky gopher frog (DGF; Lithobates sevosa) were explored to
support planned recovery efforts for this species including breeding and
augmentation of wild populations. METHODS: Body size (snout-vent length and body
weight) measurements, observation of nuptial pads, ultrasound imaging, and
urinary hormone analysis for testosterone and estrone were performed on 27 male
and 19 female DGFs. For each method, the mean and range of measurement values
were determined for male and female DGFs housed in a captive breeding population.
The ability of these methods to accurately predict the true biological sex of the
individuals was assessed retrospectively. RESULTS: Body size measurements were of
limited use for sex identification purposes, as males and females demonstrated
overlapping body lengths and weights. Observation of the presence/absence of
nuptial pads in males and females, respectively, proved to be accurate and easy
to perform in most cases. Ultrasound imaging was useful for predicting the sex of
female frogs, particularly when females were gravid. Commercial enzyme
immunoassay kits were validated to measure urinary hormones in the DGF. Mean
urinary testosterone (males: 2.22 +/- 0.38 ng/ml; females: 0.92 +/- 0.11 ng/ml)
and estrone (males: 0.08 +/- 0.01 ng/ml; females: 1.50 +/- 0.39 ng/ml)
concentrations were significantly (p < 0.05) different between the sexes.
However, there was some overlap in hormone concentrations between the sexes. When
a ratio of testosterone (T) to estrone (E) concentrations was calculated for each
individual, males demonstrated significantly greater T/E ratios compared to
females (p < 0.05). Use of this ratio showed greater accuracy in predicting the
sex of the animal compared to using testosterone or estrone concentrations alone.
CONCLUSIONS: Monitoring for presence/absence of nuptial pads and using urinary
testosterone to estrone hormone ratios were the most accurate methods for
identifying the biological sex of adult DGFs. Urinary hormone measurements for
sex identification may be useful in other weakly dimorphic and monomorphic
amphibian species in both ex situ and in situ settings.
PMID- 27484120
TI - Genetic and pathogenic difference between Streptococcus agalactiae serotype Ia
fish and human isolates.
AB - BACKGROUND: Streptococcus agalactiae (GBS) is a common pathogen to infect
newborn, woman, the elderly, and immuno-compromised human and fish. 37 fish
isolates and 554 human isolates of the GBS in 2007-2012 were investigated in
serotypes, antibiotic susceptibility, genetic difference and pathogenicity to
tilapia. RESULTS: PCR serotyping determined serotype Ia for all fish GBS isolates
and only in 3.2 % (3-4.2 %) human isolates. For fish isolates, all consisted a
plasmid less than 6 kb and belonged to ST7 type, which includes mainly pulsotypes
I and Ia, with a difference in a deletion at the largest DNA fragment. These fish
isolates were susceptible to all antimicrobials tested in 2007 and increased in
non-susceptibility to penicillin, and resistance to clindamycin and ceftriaxone
in 2011. Differing in pulsotype and lacking plasmid from fish isolates, human
serotype Ia isolates were separated into eight pulsotypes II-IX. Main clone ST23
included pulsotypes II and IIa (50 %) and ST483 consisted of pulsotype III. Human
serotype Ia isolates were all susceptible to ceftriaxone and penicillin and few
were resistant to erythromycin, azithromycin, clindamycin, levofloxacin and
moxifloxacine with the resistant rate of 20 % or less. Using tilapia to analyze
the pathogenesis, fish isolates could cause more severe symptoms, including
hemorrhage of the pectoral fin, hemorrhage of the gill, and viscous black and
common scites, and mortality (>95 % for pulsotype I) than the human isolates (<30
%); however, the fish pulostype Ia isolate 912 with deletion caused less symptoms
and the lowest mortality (<50 %) than pulsotype I isolates. CONCLUSION: Genetic,
pathogenic, and antimicrobial differences demonstrate diverse origin of human and
fish serotype Ia isolates. The pulsotype Ia of fish serotype Ia isolates may be
used as vaccine strains to prevent the GBS infection in fish.
PMID- 27484121
TI - Hemolytic anemia caused by aortic flap and inversion of felt strip after
ascending aorta replacement.
AB - BACKGROUNDS: Hemolysis related to a kinked prosthetic graft or inner felt strip
is a very rare complication after aortic surgery. We describe herein a case of
hemolytic anemia that developed due to aortic flap of the dissection and
inversion of an inner felt strip that was applied at the proximal anastomosis of
a replaced ascending aorta 10 years previously. CASE PRESENTATION: A 74-year-old
woman presented with consistent hemolytic anemia 10 years after replacement of
the ascending aorta to treat Stanford type A acute aortic dissection. The cause
of hemolysis was attributed to mechanical injury of red blood cells at a site of
stenosis caused by aortic flap of the dissection and inversion of the felt strip
used for the proximal anastomosis. Repeated resection of the strip and graft
replacement of the ascending aorta resolved this problem. CONCLUSIONS: We
considered that blood flow disrupted by a jet of blood at the site of the
proximal inner felt strip was the cause of severe hemolysis, we describe rare
hemolytic anemia at the site of aortic flap and inverted felt strip after
replacement of the ascending aorta.
PMID- 27484122
TI - Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate,
scores of the short form of the Glasgow composite measure pain scale and visual
analog scale for stress and pain behavior in dogs before and after
ovariohysterectomy.
AB - BACKGROUND: The stress reaction induced by surgery and associated pain may be
detrimental for patient recovery and should be minimized. The neuropeptide
chromogranin A (CGA) has shown promise as a sensitive biomarker for stress in
humans. Little is known about CGA and its derived peptides, catestatin (CST) and
vasostatin (VS), in dogs undergoing surgery. The objectives of this study were to
investigate and compare concentrations of CGA epitopes CST and VS, cortisol, body
temperature, heart rate, respiratory rate, scores of the short form of the
Glasgow composite measure pain scale (CMPS-SF) and visual analog scales (VAS) for
stress and pain behavior in dogs before and after ovariohysterectomy. METHODS:
Thirty healthy privately owned female dogs admitted for elective
ovariohysterectomy were included. Physical examination, CMPS-SF, pain behavior
VAS, and stress behavior VAS were recorded and saliva and blood samples were
collected before surgery, 3 h after extubation, and once at recall 7-15 days
after surgery. Dogs were premedicated with morphine and received carprofen as
analgesia for 7 days during the postoperative period. RESULTS: At 3 h after
extubation, CMPS-SF and pain behavior VAS scores had increased (p < 0.0001) and
stress behavior VAS scores, temperature, respiratory rate (p < 0.0001), plasma
CST concentrations (p = 0.002) had decreased significantly compared to before
surgery. No significant differences were observed in the subjective and
physiological parameters between before surgery and at recall, but plasma CST (p
= 0.04) and serum cortisol (p = 0.009) were significantly lower at recall. Plasma
VS, saliva CST, and heart rate did not differ significantly at any observed time.
CONCLUSION: Study parameters for evaluating surgery-induced stress and pain
changed in dogs subjected to ovariohysterectomy. To further evaluate CST and VS
usefulness as pain biomarkers, studies on dogs in acute painful situations are
warranted.
PMID- 27484123
TI - What criteria do decision makers in Thailand use to set priorities for vaccine
introduction?
AB - BACKGROUND: There is a need to identify rational criteria and set priorities for
vaccines. In Thailand, many licensed vaccines are being considering for
introduction into the Expanded Program on Immunization; thus, the government has
to make decisions about which vaccines should be adopted. This study aimed to set
priorities for new vaccines and to facilitate decision analysis. METHODS: We used
a best-worst scaling study for rank-ordering of vaccines. The candidate vaccines
were determined by a set of criteria, including burden of disease, target age
group, budget impact, side effect, effectiveness, severity of disease, and cost
of vaccine. The criteria were identified from a literature review and by in
depth, open-ended interviews with experts. The priority-setting model was
conducted among three groups of stakeholders, including policy makers, healthcare
professionals and healthcare administrators. The vaccine data were mapped and
then calculated for the probability of selection. RESULTS: From the candidate
vaccines, the probability of hepatitis B vaccine being selected by all
respondents (96.67 %) was ranked first. This was followed, respectively, by
pneumococcal conjugate vaccine-13 (95.09 %) and Haemophilus influenzae type b
vaccine (90.87 %). The three groups of stakeholders (policy makers, healthcare
professionals and healthcare administrators) showed the same ranking trends. Most
severe disease, high fever rate and high disease burden showed the highest
coefficients for criterion levels being selected by all respondents. This result
can be implied that a vaccine which can prevent most severe disease with high
disease burden and has low safety has a greater chance of being selected by
respondents in this study. CONCLUSIONS: The priority setting of vaccines through
a multiple-criteria approach could contribute to transparency and accountability
in the decision-making process. This is a step forward in the development of an
evidence-based approach that meets the need of developing country. The
methodology is generalizable but its application to another country would require
the criteria as relevant to that country.
PMID- 27484124
TI - Measuring the burden of preventable diabetic hospitalisations in the Mexican
Institute of Social Security (IMSS).
AB - BACKGROUND: The prevalence of diabetes among adults in Mexico has increased
markedly from 6.7 % in 1994 to 14.7 % in 2015. Although the main diabetic
complications can be prevented or delayed with timely and effective primary care,
a high percentage of diabetic patients have developed them imposing an important
preventable burden on Mexican society and on the health system. This paper
estimates the financial and health burden caused by potentially preventable
hospitalisations due to diabetic complications in hospitals operated by the
largest social security institution in Latin America, the Mexican Institute of
Social Security (IMSS), in the period 2007-2014. METHODS: Hospitalisations in
IMSS hospitals whose main cause was a diabetic complication were identified. The
financial burden was estimated using IMSS diagnostic-related groups. To estimate
the health burden, DALYs were computed under the assumption that patients would
not have experienced complications if they had received timely and effective
primary care. RESULTS: A total of 322,977 hospitalisations due to five diabetic
complications were identified during the period studied, of which
hospitalisations due to kidney failure and diabetic foot represent 78 %. The
financial burden increased by 8.4 % in real terms between 2007 and 2014. However,
when measured as cost per IMSS affiliate, it decreased by 11.3 %. The health
burden had an overall decrease of 13.6 % and the associated DALYs in 2014 reached
103,688. CONCLUSIONS: Resources used for the hospital treatment of diabetic
complications are then not available for other health care interventions. In
order to prevent these hospitalisations more resources might need to be invested
in primary care; the first step could be to consider the financial burden of
these hospitalisations as a potential target for switching resources from
hospital care to primary care services. However, more evidence of the
effectiveness of different primary care interventions is needed to know how much
of the burden could be prevented by better primary care.
PMID- 27484125
TI - Placenta abruption surface and perinatal outcome.
AB - OBJECTIVE: To identify the relationship between the placenta abruption (PA)
surface and the perinatal outcome. METHODS: This prospective descriptive study
was carried out from 1 February to 30 September 2014. We recruited all women
whose delivery was complicated by PA with onset preceded by the presence of
active fetal movement. PA surface was assessed by placental examination after
delivery. Main outcome measures were gestational age, Apgar score, and location
and percentage of PA. Data were analyzed using SPSS 17.0 Fisher's exact test was
used for comparison. RESULTS: PA occurred in 47 women (1.3%). Mean gestational
age was 36.0 weeks. PA percentages varied between 5% and 60%. Detachment >=45%
was always associated with stillbirth and was significantly observed in central
PA (p < 0.0002), while separation of 25-44% was associated with various degrees
of neonatal asphyxia. Compared to marginal separation of the placenta, central
separation was significantly associated with stillbirth (77.8% versus 10.5%, p <
0.0002) and perinatal death (88.9% versus 13.1%, p < 0.0001). CONCLUSION: PA
surface >=45% was associated with stillbirth. This knowledge can be helpful in
identifying the cause of stillbirth when PA is found. Central PA was
significantly associated with poor perinatal outcome and PA surface >=45%.
Therefore, its diagnosis calls for rapid intervention.
PMID- 27484126
TI - Effectiveness and cost-utility of a guided self-help exercise program for
patients treated with total laryngectomy: protocol of a multi-center randomized
controlled trial.
AB - BACKGROUND: Total laryngectomy with or without adjuvant (chemo)radiation often
induces speech, swallowing and neck and shoulder problems. Speech, swallowing and
shoulder exercises may prevent or diminish these problems. The aim of the present
paper is to describe the study, which is designed to investigate the
effectiveness and cost-utility of a guided self-help exercise program built into
the application "In Tune without Cords" among patients treated with total
laryngectomy. METHODS/DESIGN: Patients, up to 5 years earlier treated with total
laryngectomy with or without (chemo)radiation will be recruited for participation
in this study. Patients willing to participate will be randomized to the
intervention or control group (1:1). Patients in the intervention group will be
provided access to a guided self-help exercise program and a self-care education
program built into the application "In Tune without Cords". Patients in the
control group will only be provided access to the self-care education program.
The primary outcome is the difference in swallowing quality (SWAL-QOL) between
the intervention and control group. Secondary outcome measures address speech
problems (SHI), shoulder disability (SDQ), quality of life (EORTC QLQ-C30, QLQ
H&N35 and EQ-5D), direct and indirect costs (adjusted iMCQ and iPCQ measures) and
self-management (PAM). Patients will be asked to complete these outcome measures
at baseline, immediately after the intervention or control period (i.e. at 3
months follow-up) and at 6 months follow-up. DISCUSSION: This randomized
controlled trial will provide knowledge on the effectiveness of a guided self
help exercise program for patients treated with total laryngectomy. In addition,
information on the value for money of such an exercise program will be provided.
If this guided self-help program is (cost)effective for patients treated with
total laryngectomy, the next step will be to implement this exercise program in
current clinical practice. TRIAL REGISTRATION: NTR5255 Protocol version 4 date
September 2015.
PMID- 27484127
TI - Establishment of reference intervals of thyroid function tests from cord blood of
neonates in two selected hospitals, Addis Ababa, Ethiopia.
AB - BACKGROUND: Reference intervals are affected by different factors such as
lifestyle, ethnicity, age/developmental stage, gender, nutrition and other
environmental factors (Clin Biochem Rev: 29,2008). Therefore, it is obvious that
it should be established for every population in different regions even within a
country. Then the aim of this study is to establish population specific reference
intervals of thyroid stimulating hormone, free thyroxine and free triidothyronine
levels of cord blood. RESULTS: One hundred twenty three cord blood samples
collected from the umbilical cord of newborns were analyzed for thyroid
stimulating hormone, free thyroxine and free triidothyronine values. The birth
weights ranged between 2500 and 4700 g with mean (SD) value of 3241.46 (459.495)
gram. Their gestational age ranged between 37 and 44 weeks with an average of
39.74 weeks. The 2.5(th) and 97.5(th) percentiles of values were found to be 3.48
mIU/L and 27.57 mIU/L for thyroid stimulating hormone, 0.89 ng/dl and 1.53 ng/dl
for free thyroxine and 1.19 pg/ml and 2.51 pg/ml for free triidothyronine
respectively. CONCLUSION: In the present study the reference intervals of thyroid
stimulating hormone, free thyroxine and free triidothyronine were established and
based on the results obtained, were 3.48-27.56 mIU/L for thyroid stimulating
hormone, 0.89-1.53 ng/dl for free thyroxine and 1.19-2.51 pg/ml for free
triidothyronine. It has been concluded that the result can provide us with an
important baseline to establish population specific reference intervals for our
country using large scale studies.
PMID- 27484128
TI - Pathogenic Differences between Nipah Virus Bangladesh and Malaysia Strains in
Primates: Implications for Antibody Therapy.
AB - Nipah virus (NiV) is a paramyxovirus that causes severe disease in humans and
animals. There are two distinct strains of NiV, Malaysia (NiVM) and Bangladesh
(NiVB). Differences in transmission patterns and mortality rates suggest that
NiVB may be more pathogenic than NiVM. To investigate pathogenic differences
between strains, 4 African green monkeys (AGM) were exposed to NiVM and 4 AGMs
were exposed to NiVB. While NiVB was uniformly lethal, only 50% of NiVM-infected
animals succumbed to infection. Histopathology of lungs and spleens from NiVB
infected AGMs was significantly more severe than NiVM-infected animals.
Importantly, a second study utilizing 11 AGMs showed that the therapeutic window
for human monoclonal antibody m102.4, previously shown to rescue AGMs from NiVM
infection, was much shorter in NiVB-infected AGMs. Together, these data show that
NiVB is more pathogenic in AGMs under identical experimental conditions and
suggests that postexposure treatments may need to be NiV strain specific for
optimal efficacy.
PMID- 27484130
TI - Current and future treatments of alopecia areata and trichotillomania in
children.
AB - INTRODUCTION: Treatment options for hair disorders are generally very limited.
These options are even more limited in children due to the lack of trials and
clinical research. Moreover, physicians are sometimes scared to treat children
with drugs without safety data, especially because most hair disorders are
benign. AREAS COVERED: The objective of this paper is to review current and
future treatments for alopecia areata and trichotillomania, two disorders that
are sometimes encountered in differential diagnosis or even occur together and
probably affect the mental condition of the patient involved more than others.
EXPERT OPINION: Hair disorders are very stressful in paediatric population. Both
physicians and families are often unsatisfied leading to non-compliance. New
drugs with less side- effects are needed to increase the percentage of cure. It
is also crucial to refine genetic studies on alopecia areata in order to identify
new potential drugs worth studying. Moreover, studies on trichotillomania should
not be evaluated only by psychiatrics, but also by dermatologists.
PMID- 27484129
TI - Increased CSF levels of aromatic amino acids in hip fracture patients with
delirium suggests higher monoaminergic activity.
AB - BACKGROUND: To examine whether delirium in hip fracture patients was associated
with changes in the levels of amino acids and/or monoamine metabolites in
cerebrospinal fluid (CSF) and serum. METHODS: In this prospective cohort study,
77 patients admitted with an acute hip fracture to Oslo University Hospital,
Norway, were studied. The concentrations of amino acids in CSF and serum were
determined by high performance liquid chromatography. The patients were assessed
daily for delirium by the Confusion Assessment Method (pre-operatively and post
operative day 1-5 (all) or until discharge (delirious patients)). Pre-fracture
dementia status was decided by an expert panel. Serum was collected pre
operatively and CSF immediately before spinal anesthesia. RESULTS: Fifty-three
(71 %) hip fracture patients developed delirium. In hip fracture patients without
dementia (n = 39), those with delirium had significantly higher CSF levels of
tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and
the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those
without delirium. The same amino acids were also higher in CSF in delirious
patients with dementia (n = 38). The correlations between serum and CSF amino
acid levels were poor. CONCLUSION: Higher CSF levels of monoamine precursors in
hip fracture patients with delirium suggest a higher monoaminergic activity in
the central nervous system during delirium in this patient group.
PMID- 27484131
TI - Analog filtering methods improve leading edge timing performance of multiplexed
SiPMs.
AB - Multiplexing many SiPMs to a single readout channel is an attractive option to
reduce the readout complexity of high performance time of flight (TOF) PET
systems. However, the additional dark counts and shaping from each SiPM cause
significant baseline fluctuations in the output waveform, degrading timing
measurements using a leading edge threshold. This work proposes the use of a
simple analog filtering network to reduce the baseline fluctuations in highly
multiplexed SiPM readouts. With 16 SiPMs multiplexed, the FWHM coincident timing
resolution for single [Formula: see text] mm LYSO crystals was improved from 401
+/- 4 ps without filtering to 248 +/- 5 ps with filtering. With 4 SiPMs
multiplexed, using an array of [Formula: see text] mm LFS crystals the mean time
resolution was improved from 436 +/- 6 ps to 249 +/- 2 ps. Position
information was acquired with a novel binary positioning network. All experiments
were performed at room temperature with no active temperature regulation. These
results show a promising technique for the construction of high performance
multiplexed TOF PET readout systems using analog leading edge timing pickoff.
PMID- 27484133
TI - 5th Norwegian Environmental Toxicology Symposium: Recognizing, understanding, and
minimizing the impacts of human activity.
PMID- 27484132
TI - Association between SKIV2L polymorphism rs429608 and age-related macular
degeneration: A meta-analysis.
AB - PURPOSE: This study was conducted to comprehensively evaluate the potential
association of SKIV2L polymorphism rs429608 with age-related macular degeneration
(AMD) through a meta-analysis. METHODS: We performed a literature search in
EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for AMD
genetic studies published before August 30, 2015. Odds ratios (ORs) and 95%
confidence intervals (95% CIs) were calculated for single-nucleotide
polymorphisms (SNPs) using fixed-effect models or random effect models according
to between-study heterogeneity. Publication bias analyses were conducted using
Egger's test. RESULTS: A total of five studies from published articles were
included, and a total number of 2789 AMD cases and 3451 healthy controls were
tested in this meta-analysis. The results demonstrated that SKIV2L rs429608 is
associated with AMD under allelic model (A vs. G; OR = 0.52, 95% CI 0.44-0.62, p
< 0.001), heterozygous model (AG vs. GG; OR = 0.51; 95%CI, 0.38-0.68; p < 0.001;
PQ = 0.48; I2 = 0) and dominant model (AA+AG vs. GG; OR = 0.49; 95%CI 0.37-0.65;
p < 0.001; PQ = 0.44; I2 = 0), but not under other genetic models. CONCLUSIONS:
This meta-analysis showed that SKIV2L rs429608 was statistically associated with
AMD and it might exert a protective effect on AMD. Further investigations are
needed to validate the association and confirm the role of SKIV2L in AMD.
PMID- 27484134
TI - Lipid peroxidation and oxidative stress responses in juvenile salmon exposed to
waterborne levels of the organophosphate compounds tris(2-butoxyethyl)- and
tris(2-chloroethyl) phosphates.
AB - There is limited knowledge on the toxicological, physiological, and molecular
effects attributed to organophosphate (OP) compounds currently used as flame
retardants or additives in consumer products. This study investigated the effects
on oxidative stress and lipid peroxidation in juvenile Atlantic salmon liver and
brain samples after exposure to two OP compounds, tris(2-butoxyethyl) phosphate
(TBOEP) and tris(2-chloroethyl) phosphate (TCEP). In this study, groups of
juvenile Atlantic salmon were exposed using a semistatic experimental protocol
over a 7-d period to 3 different concentrations (0.04, 0.2, or 1 mg/L) of TBOEP
and TCEP. When toxicological factors such as bioaccumulation and
bioconcentration, and chemical structural characteristics and behavior, including
absorption to solid materials, are considered, these concentrations represent
environmentally relevant concentrations. The concentrations of the contaminants
were derived from levels of their environmental occurrence. The expression of
genes related to oxidative stress-glutathione peroxidase (GPx), glutathione
reductase (GR), glutathione S-transferase (GST)-and to lipid peroxidation
peroxisome proliferator-activated receptors (PPAR)-were determined using
quantitative (real-time) polymerase chain reaction (PCR). The presence of PPAR
proteins was also investigated using immunochemical methods. Levels of
thiobarbituric acid-reactive substances (TBARS) in liver were used as a measure
of lipid peroxidation. Overall, our data show an increase in lipid peroxidation,
and this was associated with an augmented expression of genes from the
glutathione family of responses. Interestingly, PPAR expression in liver after
exposure to TBOEP and TCEP was consistently decreased compared to controls, while
expression in brain did not show a similar trend. The results suggest that OP
contaminants may induce oxidative stress and thus production of reactive oxygen
substances (ROS), and modulate lipid peroxidation processes in organisms.
PMID- 27484135
TI - Behavioral responses of brown shrimp (Crangon crangon) to reduced seawater pH
following simulated leakages from sub-sea geological storage of CO2.
AB - Large-scale storage of CO2 within sub-sea geological formations is a viable
option for reducing the volume of this greenhouse gas released directly to the
atmosphere from anthropogenic activities. Risks to benthic marine life following
possible leakage of gas through the seabed from this carbon capture and storage
(CCS) initiative are not yet well established. This study examined behavior
(activity patterns) in brown shrimp (Crangon crangon), exposed to a range of
reduced seawater pH conditions (7.6, 7, or 6.5) simulating leakage scenarios of
varying scales. Brown shrimp have an endogenous rhythmicity associated with their
activity, which dictates they are most active during hours of darkness,
presumably as protection against vision-dependent predators. This endogenous
rhythm in activity continues to be expressed when shrimp are held under constant
low-light conditions in the lab and provides an ecologically relevant endpoint to
measure when examining the influence of reduced pH on the behavior of these
animals. No marked differences in activity pattern were observed between control
shrimp maintained at pH 8.1 and those at pH 7.6. However, changes in activity
were evident at pH 7 and pH 6.5, where significant shifts in timing and intensity
of activity occurred. There was an unexpected increase in activity within periods
of expected light, probably signaling efforts by shrimp to migrate away from
reduced seawater pH conditions. The loss of this important member of the benthic
community due to migration may have important consequences for many of the
resilient species that remain.
PMID- 27484136
TI - Endocrine effects of real-life mixtures of persistent organic pollutants (POP) in
experimental models and wild fish.
AB - A series of studies have assessed the occurrence, levels, and potential adverse
effects of persistent organic pollutants (POP) in fish from Lake Mjosa. In this
lake, high levels of various POP were detected in biota. Fish from the nearby
Lake Losna contain background levels of POP and served as reference (controls) in
these studies. Significantly higher prevalence of mycobacteriosis and
pathological changes were documented in burbot (Lota lota) from Mjosa compared to
burbot from Losna. Further, transcriptional profiling identified changes in gene
expression in burbot from Mjosa compared to burbot from Losna associated with
drug metabolism enzymes and oxidative stress. POP extracted from burbot liver oil
from the two lakes was used to expose zebrafish (Danio rerio) during two
consecutive generations. During both generations, POP mixtures from both lakes
increased the rate of mortality, induced earlier onset of puberty, and skewed sex
ratio toward males. However, opposite effects on weight gain were found in
exposure groups compared to controls during the two generations. Exposure to POP
from both lakes was associated with suppression of ovarian follicle development.
Analyses of genome-wide transcription profiling identified functional networks of
genes associated with weight homeostasis, steroid hormone functions, and insulin
signaling. In human cell studies using adrenocortical H295R and primary porcine
theca and granulosa cells, exposure to lake extracts from both populations
modulated steroid hormone production with significant difference from controls.
The results suggest that POP from both lakes may possess the potential to induce
endocrine disruption and may adversely affect health in wild fish.
PMID- 27484137
TI - Acute toxicity of dispersed crude oil on the cold-water copepod Calanus
finmarchicus: Elusive implications of lipid content.
AB - In this investigation, acute toxicity data were used from two previously reported
studies where cold-water copepods were exposed to mechanically dispersed (MD) and
chemically (CD) dispersed oil. In one of these studies, concentration-dependent
mortality was observed, whereas no apparent relationship between exposure
concentration and mortality was found in the other. The only marked difference
between the studies is that copepods in the first experiment displayed a lower
lipid sac volume (on average) than in the second one. In this study additional
biometric data on lipid content were utilized and observed effects and
toxicokinetics modeling applied in order to investigate whether differences in
sensitivity between copepod cohorts might be explained by differences in lipid
content. Results suggest that although a considerable lipid sac might retard
toxicokinetics, the observed differences in lipid volume are not sufficient to
explain differences in toxicity. Further, there are no apparent indications that
acute toxic stress leads to lipid depletion, or that acute increased mortality
rate selectively affects lipid-poor individuals. It is conceivable that other
potential explanations exist, but the causal relationship between lipid content
and increased mortality frequency remains elusive.
PMID- 27484138
TI - Exposure of first-feeding cod larvae to dispersed crude oil results in similar
transcriptional and metabolic responses as food deprivation.
AB - Exposure of first-feeding cod larvae (Gadus morhua) to dispersed oil results in
reduced feeding during an important transition period. First-feeding cod larvae
were subjected to a 4-d treatment of food deprivation and sampled for microarray
analyses. These microarray data were combined with data from cod larvae treated
with mechanically and chemically dispersed oil in an attempt to understand to
what extent starvation might explain some of the effects observed in first
feeding cod larvae during oil exposure. Transcriptional profiling of cod larvae
suggested that the influence of oil exposure was almost as dramatic as being
completely deprived of food. Protein and cellular degradation and loss of amino
acids and glucose appear to be concomitant responses to both oil exposure and
starvation. Fluorescence imaging of gut content indicated low uptake of food, and
reduced growth (decrease in dry weight and in carbon and nitrogen content) was
also noted in oil-exposed larvae, providing phenotypic anchoring of microarray
data. The study displays the importance in combining use of high-throughput
molecular tools with assessment of fitness-related endpoints in order to provide
a greater understanding of toxicant-induced responses. This combined-approach
investigation suggests that reduction of food uptake is an important process to
be included when predicting effects of accidental oil spills. Finally, when
comparing data from two oil treatments, exposure to chemically dispersed oil did
not appear to result in greater toxicity than exposure to mechanically dispersed
oil.
PMID- 27484139
TI - Predicting environmental risk: A road map for the future.
AB - Frameworks for environmental risk assessment (ERA) focus on comparing results
from separate exposure and effect assessments. Exposure assessment generally
relies on mechanistic fate models, whereas the effects assessment is anchored in
standard test protocols and descriptive statistics. This discrepancy prevents a
useful link between these two pillars of ERA, and jeopardizes the realism and
efficacy of the entire process. Similar to exposure assessment, effects
assessment requires a mechanistic approach to translate the output of fate models
into predictions for impacts on populations and food webs. The aim of this study
was to discuss (1) the central importance of the individual level, (2) different
strategies of dealing with biological complexity, and (3) the role that
toxicokinetic-toxicodynamic (TKTD) models, energy budgets, and molecular biology
play in a mechanistic revision of the ERA framework. Consequently, an outline for
a risk assessment paradigm was developed that incorporates a mechanistic effects
assessment in a consistent manner, and a "roadmap for the future." Such a roadmap
may play a critical role to eventually arrive at a more scientific and efficient
ERA process, and needs to be used to shape our long-term research agendas.
PMID- 27484140
TI - Individual and molecular level effects of produced water contaminants on nauplii
and adult females of Calanus finmarchicus.
AB - In the Barents Sea region new petroleum fields are discovered yearly and
extraction of petroleum products is expected to increase in the upcoming years.
Despite enhanced technology and stricter governmental legislation, establishment
of the petroleum industry in the Barents Sea may potentially introduce a new
source of contamination to the area, as some discharges of produced water will be
allowed. Whether the presence of produced water poses a risk to the Arctic marine
life remains to be investigated. The aim of this study was to examine effects of
exposure to several compounds found in produced water-a mixture of selected
organic compounds (APW), radium-226 ((226)Ra), barium (Ba), and a scale inhibitor
on the copepod species Calanus finmarchicus. Experiments were performed using
exposure concentrations at realistic levels based on those detected in the
vicinity of known discharge points. The influence of lethal and sublethal effects
on early life stages was determined and significantly lower survival in the APW
exposure groups was found. In the Ba treatment the life stage development did not
proceed to the same advanced stages as observed in the control (filtered sea
water). The scale inhibitor and (226)Ra treatments showed no significant
difference from control. In addition, adult females were exposed to APW, (226)Ra,
and a mixture of the two. Both individual-level effects (egg production and
feeding) and molecular-level effects (gene expression) were assessed. On the
individual level endpoints, only treatments including APW produced an effect
compared to control. However, on the molecular level the possibility that also
(226)Ra induced toxicologically relevant effects cannot be ruled out.
PMID- 27484141
TI - Parental exposure to natural mixtures of persistent organic pollutants (POP)
induced changes in transcription of apoptosis-related genes in offspring
zebrafish embryos.
AB - Apoptosis is an integral element of development that may also be initiated by
environmental contaminants. The aim of the present study was to assess potential
changes in the regulation of apoptotic genes in zebrafish embryos following
parental exposure to two natural mixtures of persistent organic pollutants (POP).
The mixture from Lake Mjosa contained exceptionally high concentrations of
polybrominated diphenyl ethers (PBDE), as well as relatively high levels of
polychlorinated biphenyls (PCB) and dichlorodiphenyltrichloroethane (DDT). The
mixture from Lake Losna contained background concentrations of POP. Genes
involved in the apoptotic machinery were screened for their expression profile at
four time points during embryonic development. Thirteen and 15 genes involved in
apoptosis were found to be significantly upregulated in the high-exposure and
background exposure groups, respectively, compared with controls. Modulation of
apoptotic genes was restricted only to the first time point, which corresponds
with the blastula stage. Although there were substantial differences in POP
concentrations between mixtures, genes underlying the apoptosis process showed
almost similar responses to the two mixtures. In both exposure groups the main
executors of apoptosis p53, casp 2, casp 6, cassp 8, and BAX displayed
upregulation compared to controls, suggesting that these POP induce apoptosis via
a p53-dependent mechanism. Upregulation of genes that play a critical role in
apoptosis suggests that disturbance of normal apoptotic signaling during
gametogenesis and embryogenesis may be one of the central mechanisms involved in
adverse reproductive effects produced by POP in zebrafish.
PMID- 27484142
TI - Transcriptional effects of metal-rich acid drainage water from the abandoned
Lokken Mine on Atlantic salmon (Salmo salar) smolt.
AB - Runoff of metals represents one of the major environmental challenges related to
historic and ongoing mining activity. In this study, transcriptomics (direct RNA
sequencing [RNA-seq] and reverse-transcription quantitative polymerase chain
reaction [RT-qPCR]) was used to predict toxicity of metal-rich acid mine drainage
(AMD) water collected in the abandoned copper (Cu) mine called Lokken Mine on
Atlantic salmon liver and kidney, the main target organs of Cu-induced toxicity
in fish. Smolts were exposed to control and diluted AMD water, which contains a
mixture of metals but is especially enriched with Cu, at 4 concentrations in
freshwater (FW) for 96 h, and then were transferred to and kept in seawater (SW)
for another 24 h. Significant accumulation of Cu was observed in the gills, but
not liver and kidney tissues, after 96 h of exposure. Short-term exposure to
metal-rich ADM (high exposure group) significantly upregulated 3201 transcripts
and downregulated 3782 transcripts in liver. The strongest effect attributed to
exposure was observed on the KEGG pathway "protein processing in endoplasmic
reticulum," followed by "steroid biosynthesis." Gene ontology (GO) analysis
suggested that exposure predominantly affected "protein folding," possibly by
disrupting disulfide bonds as a result of endoplasmic-reticulum-generated stress,
and "sterol biosynthetic processes." Transfer to uncontaminated SW for 24 h
amended the transcription of several genes, suggesting a transient effect of
treatment on some mechanisms. In conclusion, the data show that trace metals in
AMD from abandoned pyrite mines might disturb molecular mechanisms linked to
protein folding in Atlantic salmon smolt endoplasmic reticulum.
PMID- 27484143
TI - Biological effects of polycyclic aromatic hydrocarbons (PAH) and their first
metabolic products in in vivo exposed Atlantic cod (Gadus morhua).
AB - The monitoring of the presence of polycyclic aromatic hydrocarbons (PAH) in the
aquatic environment is a worldwide activity since some of these compounds are
well-established carcinogens and mutagens. Contaminants in this class are in fact
regarded as priority hazardous substances for environmental pollution (Water
Framework Directive 2000/60/EC). In this study, Atlantic cod (Gadus morhua) was
selected to assess in vivo effects of two PAH and their first metabolic products,
namely, the corresponding trans-dihydrodiols, using biological markers. Fish were
exposed for 1 wk to a single PAH (naphthalene or chrysene) and its synthetic
metabolites ((1R,2R)-1,2-dihydronaphthalene-1,2-diol and (1R,2R)-1,2
dihydrochrysene-1,2-diol) by intraperitoneal injection in a continuous seawater
flow system. After exposure, PAH metabolism including PAH metabolites in bile and
ethoxyresorufin O-deethylase (EROD) activity, oxidative stress glutathione S
transferases (GST) and catalase (CAT) activities, and genotoxicity such as DNA
adducts were evaluated, as well as general health conditions including condition
index (CI), hepatosomatic index (HSI), and gonadosomatic index (GSI). PAH
metabolite values were low and not significantly different when measured with the
fixed-wavelength fluorescence screening method, while the gas chromatography-mass
spectroscopy (GC-MS) method showed an apparent dose response in fish exposed to
naphthalene. DNA adduct levels >=0.16 * 10(-8) relative adduct level (RAL) were
detected. It should be noted that 0.16 * 10(-8) RAL is considered the maximal
acceptable background level for this species. The other biomarkers activities of
catalase, GST, and EROD did not display a particular compound- or dose-related
response. The GSI values were significantly lower in some chrysene- and in both
naphthalene- and naphthalene diol-exposed groups compared to control.
PMID- 27484144
TI - An evaluation of coral lophelia pertusa mucus as an analytical matrix for
environmental monitoring: A preliminary proteomic study.
AB - For the environmental monitoring of coral, mucus appears to be an appropriate
biological matrix due to its array of functions in coral biology and the non
intrusive manner in which it can be collected. The aim of the present study was
to evaluate the feasibility of using mucus of the stony coral Lophelia pertusa
(L. pertusa) as an analytical matrix for discovery of biomarkers used for
environmental monitoring. More specifically, to assess whether a mass
spectrometry-based proteomic approach can be applied to characterize the protein
composition of coral mucus and changes related to petroleum discharges at the
seafloor. Surface-enhanced laser desorption/ionization-time of flight mass
spectrometry (SELDI-TOF MS) screening analyses of orange and white L. pertusa
showed that the mucosal protein composition varies significantly with color
phenotype, a pattern not reported prior to this study. Hence, to reduce
variability from phenotype difference, L. pertusa white individuals only were
selected to characterize in more detail the basal protein composition in mucus
using liquid chromatography, mass spectrometry, mass spectrometry (LC-MS/MS). In
total, 297 proteins were identified in L. pertusa mucus of unexposed coral
individuals. Individuals exposed to drill cuttings in the range 2 to 12 mg/L
showed modifications in coral mucus protein composition compared to unexposed
corals. Although the results were somewhat inconsistent between individuals and
require further validation in both the lab and the field, this study demonstrated
preliminary encouraging results for discovery of protein markers in coral mucus
that might provide more comprehensive insight into potential consequences
attributed to anthropogenic stressors and may be used in future monitoring of
coral health.
PMID- 27484145
TI - Effect of dispersed crude oil on the feeding activity, retention efficiency, and
filtration rate of differently sized blue mussels (Mytilus edulis).
AB - The use of physiological response endpoints in environmental monitoring
represents an opportunity to provide an integrated picture of health status and
ecological fitness of individuals, and may provide an indication of potential
longer term effects on aquatic organisms in the environment. The feeding behavior
response sensitivity of blue mussels (Mytilus edulis) of differing size to
dispersed crude oil (DCO) was investigated in a lab exposure experiment. The
ability of mussels to recover following a single exposure was also investigated,
as well as the response to consecutive exposures, in order to assess the utility
of employing the same individuals in chronic environmental monitoring. Feeding
physiology was assessed by measuring retention efficiency and filtration rate of
individual mussels in a live-algae feeding assay. In addition, the percentage of
mussels actively filtering during testing was calculated. The feeding physiology
parameters were sensitive and able to discriminate exposed mussels from controls.
Further, data indicated that larger mussels appear more suitable in environmental
monitoring, as these animals showed both sensitivity and an ability to adapt and
recover from exposure while remaining sensitive to subsequent treatments. Smaller
mussels were also sensitive to the measured endpoints, even if these animals
suffered higher rates of mortality during the exposure. Finally, when exposed to
the high concentration of DCO, mussels displayed a tendency to close the valves
and terminate filtration.
PMID- 27484146
TI - p18 inhibits reprogramming through inactivation of Cdk4/6.
AB - Pluripotent stem cells (PSCs), including embryonic and induced pluripotent stem
cells (iPSCs), show atypical cell cycle regulation characterized by a high
proliferation rate and a shorter G1 phase compared with somatic cells. The
mechanisms by which somatic cells remodel their cell cycle to achieve the high
proliferation rate of PSCs during reprogramming are unclear. Here we identify
that the Ink4 protein p18, which is expressed at high levels in somatic cells but
at low levels in PSCs, is a roadblock to successful reprogramming. Mild
inhibition of p18 expression enhances reprogramming efficiency, while ectopic
expression of p18 completely blocks reprogramming. Mechanistic studies show that
expression of wild-type p18, but not a p18(D68N) mutant which cannot inhibit
Cdk4/6, down-regulates expression of Cdk4/6 target genes involved in DNA
synthesis (TK, TS, DHFR, PCNA) and cell cycle regulation (CDK1 and CCNA2) and
thus inhibits reprogramming. These results indicate that p18 blocks reprogramming
by targeting Cdk4/6-mediated cell cycle regulation. Taken together, our results
define a novel pathway that inhibits somatic cell reprogramming, and provide a
new target to enhance reprogramming efficiency.
PMID- 27484147
TI - Chronic myeloid leukemia patients call for quality and consistency when generics
are introduced to treat their cancer.
PMID- 27484148
TI - Analysis of different components in the peritumoral tissue microenvironment of
colorectal cancer: A potential prospect in tumorigenesis.
AB - The present study aimed to observe the varying expression of biomarkers in the
microenvironment adjacent to colorectal cancer lesions to provide additional
insight into the functions of microenvironment components in carcinogenesis and
present a novel or improved indicator for early diagnosis of cancer. A total of
144 human samples from three different locations in 48 patients were collected,
these locations were 10, 5 and 2 cm from the colorectal cancer lesion,
respectively. The biomarkers analyzed included E-cadherin, cytokeratin 18 (CK18),
hyaluronidase-1 (Hyal-1), collagen type I (Col-I), Crumbs3 (CRB3), vimentin,
proteinase activated receptor 3 (PAR-3), alpha-smooth muscle actin (alpha-SMA),
cyclin D1 (CD1) and cluster of differentiation (CD)133. In addition, crypt
architecture was observed. Related functional analysis of proteins was performed
using hierarchical index cluster analysis. More severe destroyed crypt
architecture closer to the cancer lesions was observed compared with the 10 cm
sites, with certain crypts degraded entirely. Expression levels of E-cadherin,
CK18, CRB3 and PAR-3 were lower in 2 cm sites compared with the 10 cm sites (all
P<0.001), while the expression levels of the other biomarkers in the 2 cm sites
were increased compared with 10 cm sites (all P<0.0001). Notably, the expression
of CK18 in 2 cm sites was higher than in the 5 cm site (P<0.0001), which was
different from the expression of E-cadherin, CRB3 and PAR-3. The expression
levels of Hyal-1 and Col-I at the 2 cm sites were lower than that of the 5 cm
sites (P>0.05 and P=0.0001, respectively), while the expression of vimentin,
alpha-SMA, CD1 and CD133 were not. Hyal-1 and Col-I may be independently
important in cancer initiation in the tumor microenvironment. The results of the
present study suggest that the biomarkers in the tissue microenvironment are
associated with early tumorigenesis and may contribute to the development of
carcinomas. These observations may be useful for early diagnosis of colorectal
cancer.
PMID- 27484150
TI - Spatiotemporal dynamics of autophagy receptors in selective mitophagy.
AB - Damaged mitochondria are turned over through a process of selective autophagy
termed mitophagy. In mitophagy, unhealthy mitochondria are recognized and
ubiquitinated by Parkinson disease-linked proteins PINK1 and PARK2. The
subsequent recruitment of ubiquitin-binding autophagy receptors leads in turn to
the sequestration of the damaged organelles into LC3-positive phagophores,
precursors to autophagosomes. The precise identity of these receptors and how
they are regulated has been the focus of considerable attention. Our recent work
uses live-cell imaging to explore the dynamics and regulation of autophagy
receptor recruitment. Utilizing multiple paradigms to induce mitochondrial
damage, we identified the rapid, 2-step recruitment of autophagy receptors OPTN,
CALCOCO2/NDP52, and TAX1BP1. All 3 receptors are recruited to damaged
mitochondria with similar kinetics; however, only OPTN is necessary for efficient
formation of a phagophore sequestering damaged mitochondria from the cytosol.
OPTN is co-recruited to damaged mitochondria along with its upstream kinase TBK1.
Depletion of OPTN or TBK1, or expression of amyotrophic lateral sclerosis (ALS)
linked mutations in either protein, interfere with efficient autophagic
engulfment of depolarized mitochondria. These observations suggest that
insufficient autophagy of damaged mitochondria may contribute to
neurodegenerative disease.
PMID- 27484149
TI - Perceived Risk of HIV Infection Among Drug-Using African American Male Prisoners:
One Year After Community Re-entry.
AB - BACKGROUND: African Americans represent 13% of the U.S. population but 46% of
people living with HIV and nearly 40% of state and federal prisoners.
Disproportionate rates of HIV among African American males involved in the
criminal justice system have been associated with risk factors, including:
contracting sexually transmitted infections (STIs), substance misuse, and
inconsistent condom use. However, many African American males may not perceive an
elevated risk of HIV upon re-entering the community. OBJECTIVE: The current study
examines correlates of perceived HIV risk among incarcerated African American
drug-using males about one year after release from prison. METHODS: Derived from
a larger Health Services Utilization study, interviewing (N = 661) incarcerated
men at baseline with a 92% follow-up rate approximately one year after community
re-entry, the current study is a secondary data analyses from self-identified
African American men (N = 250). After list-wise deletion, the total N = 221 for
the final study results. RESULTS: An ordered logistic regression model examining
perceived risk of HIV as the dependent variable found age, cocaine use before
sex, and condom use were significant correlates in the model. Alcohol use before
sex mediated the relationship between cocaine use before sex and perceived HIV
risk. CONCLUSIONS: Results suggest men in this study are engaged in HIV risk
behaviors and risk perception varies. Implications for individual-level,
community-level and policy interventions are discussed.
PMID- 27484151
TI - Thyroid Function Characteristics and Determinants: The Rotterdam Study.
AB - BACKGROUND: Information on determinants and change of thyroid function over time
is sparse and conflicting but crucial for clinical interpretation and research.
Therefore, our aim was to systematically investigate determinants of thyroid
stimulating hormone (TSH), free thyroxine (FT4) (as markers of thyroid function),
their mutual relation (as marker of thyroid function set point) and changes in
thyroid function over time. METHODS: We included 9402 participants from the
Rotterdam Study not taking thyroid medication and with available thyroid function
measurements. Repeated measurements (6.5-year interval) were available for 1225
participants. The association of selected determinants with TSH, FT4, and their
mutual relation (reflecting thyroid function set point) was estimated using
linear regression models using restricted cubic splines with three knots. The
factors investigated were age, sex, body mass index (BMI), tobacco smoking,
alcohol use, thyroperoxidase antibodies (TPOAb), and common genetic factors.
RESULTS: Most influential determinants of TSH were age, smoking, genetic
determinants, and TPOAb levels (p < 0.001). For FT4, most influential
determinants were age, BMI, sex, genetic determinants and TPOAb levels (p <
0.001). Older age, female sex, and increased TPOAb levels were associated with a
stronger relation between TSH and FT4. TSH levels did not change over time,
irrespective of age. FT4 levels increased over time, most prominently in those
older than 65 years of age (mean increase of 4.5 pmol/L). CONCLUSIONS: The main
factors that influence the relationship between thyroid hormone and molar
concentrations of TSH in our population-based cohort study are age, smoking, BMI,
TPOAb levels, and common genetic variants. The set point that determines TSH
secretion as it relates to negative thyroid hormone feedback is modified by age,
sex and TPOAb positivity. FT4 levels increase over time, with a more pronounced
increase in the elderly, while TSH values seem stable over time. Our results
question the current notion of an increase of TSH with increasing age.
PMID- 27484152
TI - Predictors of Cell Phone Use in Distracted Driving: Extending the Theory of
Planned Behavior.
AB - This study examines the predictors of six distracted driving behaviors, and the
survey data partially support Ajzen's (1991) Theory of Planned Behavior (TPB).
The data suggest that the attitude variable predicted intention to engage in all
six distracted driving behaviors (reading and sending text messages, making and
answering cell phone calls, reading/viewing social media, and posting on social
media while driving). Extending the model to include past experience and the
variable perceived safety of technology yielded an improvement in the prediction
of the distraction variables. Specifically, past experience predicted all six
distracted driving behaviors, and the variable perceived safety of technology
predicted intentions to read/view social media and intention to post on social
media while driving. The study provides evidence for the importance of
incorporating expanded variables into the original TPB model to predict cell
phone use behaviors while driving, and it suggests that it is essential to tailor
campaign materials for each specific cell phone use behavior to reduce distracted
driving.
PMID- 27484153
TI - Acute effects of small changes in crank length on gross efficiency and pedalling
technique during submaximal cycling.
AB - The main purpose of this study was to assess the acute effects of small changes
in crank length (assumable by competitive cyclists) on metabolic cost and
pedalling technique during submaximal cycling. Twelve amateur road cyclists
performed three sets of submaximal pedalling (150, 200 and 250 W) at a constant
cadence (91.3 +/- 0.8 rpm) in a randomised order with three commonly used crank
lengths, preferred (172.5-175 mm), +5 mm and -5 mm. Energy cost of pedalling,
kinetic and kinematic variables were simultaneously registered. Changes in crank
length had no significant effect on heart rate (144 +/- 13, 145 +/- 12 and 145 +/
13 bpm, respectively) and gross efficiency (GE) (20.4 +/- 2.1, 20.1 +/- 2.2 and
20.3 +/- 2.4%, respectively). A longer crank induced a significant (P < 0.05)
reduction of positive impulse proportion (PIP) (0.9-1.9%) due to a greater
maximum (1.0-2.3 N . m) and minimum torque (1.0-2.2 N . m). At the same time, the
maximum flexion and range of motion of the hip and knee joints were significantly
increased (1.8-3.4 degrees and P < 0.05), whereas the ankle joint was not
affected. In conclusion, the biomechanical changes due to a longer crank did not
alter the metabolic cost of pedalling, although they could have long-term adverse
effects. Therefore, in case of doubt between two lengths, the shorter one might
be recommended.
PMID- 27484154
TI - Mutations induce conformational changes in folliculin C-terminal domain: possible
cause of loss of guanine exchange factor activity and Birt-Hogg-Dube syndrome.
PMID- 27484155
TI - Keep in touch (KIT): perspectives on introducing internet-based communication and
information technologies in palliative care.
AB - BACKGROUND: Hospitalized palliative patients need to keep in touch with their
loved ones. Regular social contact may be especially difficult for individuals on
palliative care in-patient units due to the isolating nature of hospital
settings. Technology can help mitigate isolation by facilitating social
connection. This study aimed to explore the acceptability of introducing internet
based communication and information technologies for patients on a palliative
care in-patient unit. METHODS: In the first phase of the Keep in Touch (KIT)
project, a diverse group of key informants were consulted regarding their
perspectives on web-based communication on in-patient palliative care units.
Participants included palliative patients, family members, direct care providers,
communication and information technology experts, and institutional
administrators. Data was collected through focus groups, interviews and drop-in
consultations, and was analyzed for themes, consensus, and major differences
across participant groups. RESULTS: Hospitalized palliative patients and their
family members described the challenges of keeping in touch with family and
friends. Participants identified numerous examples of ways that communication and
information technologies could benefit patients' quality of life and care.
Patients and family members saw few drawbacks associated with the use of such
technology. While generally supportive, direct care providers were concerned that
patient requests for assistance in using the technology would place increased
demands on their time. Administrators and IT experts recognized issues such as
privacy and costs related to offering these technologies throughout an
organization and in the larger health care system. CONCLUSIONS: This study
affirmed the acceptability of offering internet-based communication and
information technologies on palliative care in-patient units. It provides the
foundation for trialing these technologies on a palliative in-patient unit.
Further study is needed to confirm the feasibility of offering these technologies
at the bedside.
PMID- 27484156
TI - The use of DNA barcodes in food web construction-terrestrial and aquatic
ecologists unite!
AB - By depicting who eats whom, food webs offer descriptions of how groupings in
nature (typically species or populations) are linked to each other. For asking
questions on how food webs are built and work, we need descriptions of food webs
at different levels of resolution. DNA techniques provide opportunities for
highly resolved webs. In this paper, we offer an expose of how DNA-based
techniques, and DNA barcodes in particular, have recently been used to construct
food web structure in both terrestrial and aquatic systems. We highlight how such
techniques can be applied to simultaneously improve the taxonomic resolution of
the nodes of the web (i.e., the species), and the links between them (i.e., who
eats whom). We end by proposing how DNA barcodes and DNA information may allow
new approaches to the construction of larger interaction webs, and overcome some
hurdles to achieving adequate sample size. Most importantly, we propose that the
joint adoption and development of these techniques may serve to unite approaches
to food web studies in aquatic and terrestrial systems-revealing the extent to
which food webs in these environments are structured similarly to or differently
from each other, and how they are linked by dispersal.
PMID- 27484157
TI - Expression of interferon regulatory factor 5 is regulated by the Sp1
transcription factor.
AB - The transcription factor, interferon regulatory factor 5 (IRF5), is important in
the induction of type I interferon, proinflammatory cytokines and chemokines, and
is involved in autoimmune diseases and tumourigenesis. However, the mechanisms
underlying the transcriptional regulation of wild-type IRF5 remain to be fully
elucidated. The present study was primarily designed to clarify whether
specificity protein 1 (Sp1) was involved in the regulation of IRF5. Initially,
the IRF5 promoter region was cloned and its promoter activity was examined using
Hela and HEK 293 cells. Deletion analyses revealed that the region spanning -179
to +62 was the minimal promoter of IRF5. Bioinformatics analyses showed that this
region contained three putative Sp1 binding sites, and mutational analyses
revealed that all the Sp1 sites contributed to transcriptional activity.
Secondly, the overexpression of Sp1 was found to increase the activity of the
IRF5 promoter and the mRNA level of IRF5, determined using reporter gene assays
and polymerase chain reaction analysis, respectively. By contrast, treatment with
mithramycin and Sp1 small interfering RNA significantly reduced the activity of
the IRF5 promoter and the mRNA level of IRF5. Finally, the results of an
electrophoretic mobility shift assay and a chromatin immunoprecipitation assay
demonstrated that Sp1 bound to the promoter region of IRF5 in vitro and in vivo.
These results suggested that the Sp1 transcription factor is the primary
determinant for activating the basal transcription of the IRF5.
PMID- 27484158
TI - Cost-effectiveness of a herpes zoster vaccination program among the French
elderly people.
AB - A vaccine against herpes zoster (HZ) and its complications has already proven
safe and effective against infection and pain and against the related
deterioration of quality of life in the elderly. In order to inform the
vaccination decision-making process regarding inclusion of this vaccine in the
French immunization schedule, we assessed the cost-effectiveness of several
vaccination scenarios, compared to no vaccination. We chose to use a previously
published Markov model. Starting vaccination in elderly individuals aged 65, 70
and 75 y old appears more cost-effective than vaccination for those aged 60 y
old, with a cost-effectiveness ratio between 30,000 and 35,000 euros per quality
adjusted-life year (QALY) gained for the first 3 age groups versus 54,500 ?; for
the latter group. These results largely contributed to the recommendation to
include the HZ vaccination in the French immunization schedule for people aged
between 65 and 74 y old in France.
PMID- 27484159
TI - Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA)
for the treatment of acute ischaemic stroke.
AB - BACKGROUND: The objective of this study was to characterize the comorbidities in
a population of patients with an acute ischaemic stroke, comparing patients that
received recombinant tissue plasminogen activator (rt-PA) to those that did not
receive rt-PA. METHOD: In a retrospective sample of 663 patients admitted for
acute ischaemic stroke, this study analysed the effects of co-morbid conditions
in the use of rt-PA. It determined non-cerebrovascular risk factors
(comorbidities) that differentiate patients who received rt-PA from those who did
not receive rt-PA. RESULT: Patients with a history of carotid stenosis, CHF and
previous strokes are significantly (p < 0.05) associated with high risk of not
receiving rt-PA. A significant number of patients with a history of hypertension
and smoking received rt-PA (p < 0.05). CONCLUSION: The findings indicate that
certain risk factors including carotid stenosis, CHF and previous stroke history
impact the treatment of patients with acute ischaemic stroke, specifically the
decision to administer rt-PA. Treatment with rt-PA is dependent on stroke
severity and onset to treatment time, but the findings suggest that rt-PA use may
also depend on patient comorbidities.
PMID- 27484160
TI - Structural modulation of lithium metal-electrolyte interface with three
dimensional metallic interlayer for high-performance lithium metal batteries.
AB - The use of lithium (Li) metal anodes has been reconsidered because of the
necessity for a higher energy density in secondary batteries. However, Li metal
anodes suffer from 'dead' Li formation and surface deactivation which
consequently form a porous layer of redundant Li aggregates. In this work, a
fibrous metal felt (FMF) as a three-dimensional conductive interlayer was
introduced between the separator and the Li metal anode to improve the
reversibility of the Li metal anode. The FMF can facilitate charge transfer in
the porous layer, rendering it electrochemically more active. In addition, the
FMF acted as a robust scaffold to accommodate Li deposits compactly in its
interstitial sites. The FMF-integrated Li metal (FMF/Li) electrode operated with
a small polarisation even at a current density of 10 mA cm(-2), and it exhibited
a seven times longer cycle-life than that of an FMF-free Li electrode in a
symmetric cell configuration. A Li metal battery (LMB) using the FMF/Li electrode
and a LiFePO4 electrode exhibited a two-fold increase in cycling stability
compared with that of a bare Li metal electrode, demonstrating the practical
effectiveness of this approach for high performance LMBs.
PMID- 27484161
TI - ZnCr2S4: Highly effective photocatalyst converting nitrate into N2 without over
reduction under both UV and pure visible light.
AB - We propose several superiorities of applying some particular metal sulfides to
the photocatalytic nitrate reduction in aqueous solution, including the high
density of photogenerated excitons, high N2 selectivity (without over-reduction
to ammonia). Indeed, ZnCr2S4 behaved as a highly efficient photocatalyst, and
with the assistance of 1 wt% cocatalysts (RuOx, Ag, Au, Pd, or Pt), the
efficiency was greatly improved. The simultaneous loading of Pt and Pd led to a
synergistic effect. It offered the highest nitrate conversion rate of ~45 mg N/h
together with the N2 selectivity of ~89%. Such a high activity remained steady
after 5 cycles. The optimal apparent quantum yield at 380 nm was 15.46%. More
importantly, with the assistance of the surface plasma resonance effect of Au,
the visible light activity achieved 1.352 mg N/h under full arc Xe-lamp, and
0.452 mg N/h under pure visible light (lambda > 400 nm). Comparing to the
previous achievements in photocatalytic nitrate removal, our work on ZnCr2S4
eliminates the over-reduction problem, and possesses an extremely high and steady
activity under UV-light, as well as a decent conversion rate under pure visible
light.
PMID- 27484162
TI - Leveraging the power of pooled data for cancer outcomes research.
AB - BACKGROUND: Clinical trials continue to be the gold standard for determining the
efficacy of novel cancer treatments, but they may also expose participants to the
potential risks of unpredictable or severe toxicities. The development of
validated tools that better inform patients of the benefits and risks associated
with clinical trial participation can facilitate the informed consent process.
The design and validation of such instruments are strengthened when we leverage
the power of pooled data analysis for cancer outcomes research. MAIN BODY: In a
recent study published in the Journal of Clinical Oncology entitled "Determinants
of early mortality among 37,568 patients with colon cancer who participated in 25
clinical trials from the adjuvant colon cancer endpoints database," using a large
pooled analysis of over 30,000 study participants who were enrolled in clinical
trials of adjuvant therapy for early-stage colon cancer, we developed and
validated a nomogram depicting the predictors of early cancer mortality. This
database of pooled individual-level data allowed for a comprehensive analysis of
poor prognostic factors associated with early death; furthermore, it enabled the
creation of a nomogram that was able to reliably capture and quantify the benefit
to-risk profile for patients who are considering clinical trial participation.
This tool can facilitate treatment decision-making discussions. CONCLUSION: As
China and other Asian countries continue to conduct oncology clinical trials,
efforts to collate patient-level information from these studies into a large data
repository should be strongly considered since pooled data can increase future
capacity for cancer outcomes research, which, in turn, can enhance patient
physician discussions and optimize clinical care.
PMID- 27484163
TI - Reviewing the Nutrition and Health Claims Regulation (EC) No. 1924/2006: What do
we know about its challenges and potential impact on innovation?
AB - Health claims potentially represent an opportunity for firms to engage in product
differentiation and thereby induce investment into R&D and innovation in the food
sector. The Nutrition and Health Claims Regulation (EC) No. 1924/2006 (NHCR) aims
at protecting and promoting innovation as one of its objectives. However,
existing studies indicate that this regulation may create several challenges for
innovation in the food sector. To this end, we review the challenges related to
the NHCR (Article 13.1) and its impact on innovation. Extant literature suggests
that companies face challenges related to changing list of ingredients, missing
transparency, wording of claims, limited financial resources, limited R&D
resources, switching product categories and abandoning the functional foods
sector. Moreover, current studies imply that so far the NHCR (in specific Article
13.1) does not seem to encourage innovation in the EU food sector.
PMID- 27484165
TI - Huge enhancement of upconversion luminescence by broadband dye sensitization of
core/shell nanocrystals.
AB - Upconversion nanocrystals (UCNCs) hold promise for bioimaging, solar cells,
photocatalysis and volumetric displays. However, their upconversion luminescence
intensities are usually low due to the weak and narrowband near-infrared
absorption of lanthanide ions. Herein, we introduce and validate a strategy to
hugely enhance upconversion luminescence intensity by using an organic near
infrared dye as an antenna to sensitize core/shell UCNCs. The dye can increase
absorptivity and broaden the absorption spectrum of the UCNCs. Such dye
sensitization, in combination with a core/shell structure, can tremendously
enhance the upconversion luminescence (UCL) intensity of the UCNCs. The UCL
intensity of dye-sensitized UCNCs excited at 820 nm is 800-folds higher than that
of pure UCNCs excited at 980 nm. Further enhancement can be obtained by
optimization of the dye emission and UCNC absorption spectral overlap. Moreover,
the proposed approach can be extended to cover any part of the solar spectrum by
using a set of dyes. This work provides new insights into the efficient
enhancement of upconversion luminescence of the UCNCs and facilitates their
applications.
PMID- 27484164
TI - High fat diet-induced TGF-beta/Gbb signaling provokes insulin resistance through
the tribbles expression.
AB - Hyperglycemia, hyperlipidemia, and insulin resistance are hallmarks of obesity
induced type 2 diabetes, which is often caused by a high-fat diet (HFD). However,
the molecular mechanisms underlying HFD-induced insulin resistance have not been
elucidated in detail. In this study, we established a Drosophila model to
investigate the molecular mechanisms of HFD-induced diabetes. HFD model flies
recapitulate mammalian diabetic phenotypes including elevated triglyceride and
circulating glucose levels, as well as insulin resistance. Expression of glass
bottom boat (gbb), a Drosophila homolog of mammalian transforming growth factor
beta (TGF-beta), is elevated under HFD conditions. Furthermore, overexpression of
gbb in the fat body produced obese and insulin-resistant phenotypes similar to
those of HFD-fed flies, whereas inhibition of Gbb signaling significantly
ameliorated HFD-induced metabolic phenotypes. We also discovered that tribbles, a
negative regulator of AKT, is a target gene of Gbb signaling in the fat body.
Overexpression of tribbles in flies in the fat body phenocopied the metabolic
defects associated with HFD conditions or Gbb overexpression, whereas tribbles
knockdown rescued these metabolic phenotypes. These results indicate that HFD
induced TGF-beta/Gbb signaling provokes insulin resistance by increasing tribbles
expression.
PMID- 27484166
TI - Infrared matrix-assisted laser desorption electrospray ionization mass
spectrometry imaging analysis of biospecimens.
AB - Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)
mass spectrometry imaging (MSI) is a technique well suited for analysis of
biological specimens. This tutorial review focuses on recent advancements and
applications of IR-MALDESI MSI to better understand key biological questions.
Through optimization of user-defined source parameters, comprehensive and
quantitative MSI data can be obtained for a variety of analytes. The effect of an
ice matrix layer is well defined in the context of desorption dynamics and
resulting ion abundance. Optimized parameters and careful control of conditions
affords quantitative MSI data which provides valuable information for targeted,
label-free drug distribution studies and untargeted metabolomic datasets.
Challenges and limitations of MSI using IR-MALDESI are addressed in the context
of the bioimaging field.
PMID- 27484167
TI - Dislocation Reduction and Stress Relaxation of GaN and InGaN Multiple Quantum
Wells with Improved Performance via Serpentine Channel Patterned Mask.
AB - The existence of high threading dislocation density (TDD) in GaN-based epilayers
is a long unsolved problem, which hinders further applications of defect
sensitive GaN-based devices. Multiple-modulation of epitaxial lateral overgrowth
(ELOG) is used to achieve high-quality GaN template on a novel serpentine channel
patterned sapphire substrate (SCPSS). The dislocation blocking brought by the
serpentine channel patterned mask, coupled with repeated dislocation bending, can
reduce the dislocation density to a yet-to-be-optimized level of ~2 * 10(5) to 2
* 10(6) cm(-2). About 80% area utilization rate of GaN with low TDD and stress
relaxation is obtained. The periodical variations of dislocation density, optical
properties and residual stress in GaN-based epilayers on SCPSS are analyzed. The
quantum efficiency of InGaN/GaN multiple quantum wells (MQWs) on it can be
increased by 52% compared with the conventional sapphire substrate. The reduced
nonradiative recombination centers, the enhanced carrier localization, and the
suppressed quantum confined Stark effect, are the main determinants of improved
luminous performance in MQWs on SCPSS. This developed ELOG on serpentine shaped
mask needs no interruption and regrowth, which can be a promising candidate for
the heteroepitaxy of semipolar/nonpolar GaN and GaAs with high quality.
PMID- 27484169
TI - The gestational diabetes tsunami: Can we survive it?
PMID- 27484171
TI - Clostridium difficile PCR ribotypes 001 and 176 - the common denominator of C.
difficile infection epidemiology in the Czech Republic, 2014.
AB - In 2014, 18 hospitals in the Czech Republic participated in a survey of the
incidence of Clostridium difficile infections (CDI) in the country. The mean CDI
incidence was 6.1 (standard deviation (SD):7.2) cases per 10,000 patient bed-days
and 37.8 cases (SD: 41.4) per 10,000 admissions. The mean CDI testing frequency
was 39.5 tests (SD: 25.4) per 10,000 patient bed-days and 255.8 tests (SD: 164.0)
per 10,000 admissions. A total of 774 C. difficile isolates were investigated, of
which 225 (29%) belonged to PCR ribotype 176, and 184 isolates (24%) belonged to
PCR ribotype 001. Multilocus variable-number tandem repeat analysis (MLVA)
revealed 27 clonal complexes formed by 84% (190/225) of PCR ribotype 176
isolates, and 14 clonal complexes formed by 77% (141/184) of PCR ribotype 001
isolates. Clonal clusters of PCR ribotypes 176 and 001 were observed in 11 and 7
hospitals, respectively. Our data demonstrate the spread of two C. difficile PCR
ribotypes within 18 hospitals in the Czech Republic, stressing the importance of
standardising CDI testing protocols and implementing mandatory CDI surveillance
in the country.
PMID- 27484170
TI - Identification of a PTPN11 hot spot mutation in a child with atypical LEOPARD
syndrome.
AB - LEOPARD syndrome (LS) is an autosomal dominant inherited disorder primarily
caused by mutations in the PTPN11, RAF1 and BRAF genes. Characteristic features
include lentigines, craniofacial dysmorphism, myocardium or valve abnormalities,
eletrocardiographic conduction defects and deafness. LS, neurofibromatosis type
1, Noonan syndrome and Legius syndrome are a group of highly overlapped disorders
termed 'RASopathies'. Therefore, clinical discrimination between these syndromes
represents a huge challenge. The present study reports a young child diagnosed
with LS via identification of a common p.Thr468Met mutation in PTPN11. Taking
into account two Taiwanese LS cases with an identical mutation, Thr468Met is
likely to be the most prevalent mutation in the Chinese population. Furthermore,
this study suggests that a clinical diagnosis of LS should be considered for
individuals with congenital cardiac defects and atypical lentigines (i.e., light
brown freckles) scattered particularly on the face.
PMID- 27484172
TI - The Human Capital of Knowledge Brokers: An analysis of attributes, capacities and
skills of academic teaching and research faculty at Kenyan schools of public
health.
AB - BACKGROUND: Academic faculty involved in public health teaching and research
serve as the link and catalyst for knowledge synthesis and exchange, enabling the
flow of information resources, and nurturing relations between 'two distinct
communities' - researchers and policymakers - who would not otherwise have the
opportunity to interact. Their role and their characteristics are of particular
interest, therefore, in the health research, policy and practice arena,
particularly in low- and middle-income countries. We investigated the individual
attributes, capacities and skills of academic faculty identified as knowledge
brokers (KBs) in schools of public health (SPH) in Kenya with a view to informing
organisational policies around the recruitment, retention and development of
faculty KBs. METHODS: During April 2013, we interviewed 12 academics and faculty
leadership (including those who had previously been identified as KBs) from six
SPHs in Kenya, and 11 national health policymakers with whom they interact. Data
were qualitatively analyzed using inductive thematic analysis to unveil key
characteristics. RESULTS: Key characteristics of KBs fell into five categories:
sociodemographics, professional competence, experiential knowledge, interactive
skills and personal disposition. KBs' reputations benefitted from their
professional qualifications and content expertise. Practical knowledge in policy
relevant situations, and the related professional networks, allowed KB's to
navigate both the academic and policy arenas and also to leverage the necessary
connections required for policy influence. Attributes, such as respect and a
social conscience, were also important KB characteristics. CONCLUSION: Several
changes in Kenya are likely to compel academics to engage increasingly with
policymakers at an enhanced level of debate, deliberation and discussion in the
future. By recognising existing KBs, supporting the emergence of potential KBs,
and systematically hiring faculty with KB-specific characteristics, SPHs can
enhance their collective human capital and influence on public health policy and
practice. Capacity strengthening of tangible skills and recognition of less
tangible personality characteristics could contribute to enhanced academic
policymaker networks. These, in turn, could contribute to the relevance of SPH
research and teaching programs as well as evidence-informed public health
policies.
PMID- 27484173
TI - The beneficial effects of cognitive training with simple calculation and reading
aloud in an elderly postsurgical population: study protocol for a randomized
controlled trial.
AB - BACKGROUND: This project proposes a pilot study to investigate the positive
healing effects of cognitive training with simple arithmetic and reading aloud on
elderly postsurgical patients. Elderly patients undergoing surgery have an
increased risk of Postoperative Cognitive Decline (POCD), a condition in which
learning, memory, and processing speed is greatly reduced after surgery. Since
elderly patients are more likely to exhibit symptoms of POCD, the incidence is
increasing as the population receiving surgery has aged. Little effort has been
expended, however, to find treatments for POCD. Learning therapy, which consists
of a combination of reading aloud and solving simple arithmetic problems, was
developed in Japan as a treatment for Alzheimer's Disease to improve cognitive
functions. Because patients with Alzheimer's Disease experience similar issues as
those with POCD in learning, memory, and processing speed, a cognitive
intervention based on the learning-therapy treatments used for Alzheimer's
Disease could show advantageous outcomes for those at risk of POCD.
METHODS/DESIGN: Cognitive function will be measured before and after surgery
using three different tests (Mini-Mental Status Exam, Frontal Assessment Battery,
and Cogstate computerized tests). Subjects will be randomly divided into two
groups-one that receives a Simple Calculation and Reading Aloud intervention
(SCRA) and a waitlisted control group that does not receive SCRA. To measure
cognition before and after the intervention, the previously mentioned three tests
will be used. The obtained data will be analyzed using statistical tests such as
ANCOVA to indicate whether the cognitive intervention group has made improvements
in their cognitive functions. In addition, questionnaires will also be
administered to collect data on mental and emotional statuses. DISCUSSION: This
report will be the first pilot study to investigate the beneficial effects of
SCRA on elderly surgical patients. Previous studies have shown sufficient
evidence on the effectiveness of learning therapy in healthy elderly people and
in those with Dementia. Therefore, this study will clarify whether SCRA can
improve cognitive function in the more specialized group of elderly surgical
patients. TRIAL REGISTRATION: University Hospital Medical Information Network
Clinical Trial Registry, UMIN000019832 . Registered on 18 November 2015.
PMID- 27484174
TI - A novel role for STOMATAL CARPENTER 1 in stomata patterning.
AB - BACKGROUND: Guard cells (GCs) are specialised cells within the plant epidermis
which form stomatal pores, through which gas exchange can occur. The GCs derive
through a specialised lineage of cell divisions which is specified by the
transcription factor SPEECHLESS (SPCH), the expression of which can be detected
in undifferentiated epidermal cells prior to asymmetric division. Other
transcription factors may act before GC specification and be required for correct
GC patterning. Previously, the DOF transcription factor STOMATAL CARPENTER 1
(SCAP1) was shown to be involved in GC function, by activating a set of GC
specific genes required for GC maturation and activity. It is thus far unknown
whether SCAP1 can also affect stomatal development. RESULTS: Here we show that
SCAP1 expression can also be observed in young leaf primordia, before any GC
differentiation occurs. The study of transgenic plants carrying a proSCAP1:GUS
GFP transcriptional fusion, coupled with qPCR analyses, indicate that SCAP1
expression peaks in a temporal window which is coincident with expression of
stomatal patterning genes. Independent scap1 loss-of-function mutants have a
reduced number of GCs whilst SCAP1 over expression lines have an increased number
of GCs, in addition to altered GC distribution and spacing patterns. The study of
early markers for stomatal cell lineage in a background carrying gain-of-function
alleles of SCAP1 revealed that, compared to the wild type, an increased number of
protodermal cells are recruited in the GC lineage, which is reflected in an
increased number of meristemoids. CONCLUSIONS: Our results suggest an early role
for SCAP1 in GC differentiation. We propose that a function of SCAP1 is to
integrate different aspects of GC biology including specification, spacing,
maturation and function.
PMID- 27484175
TI - Editorial (Mini Thematic Isssue: Learning and Well-Being in Later Life).
PMID- 27484176
TI - Screening differential circular RNA expression profiles reveals the regulatory
role of circTCF25-miR-103a-3p/miR-107-CDK6 pathway in bladder carcinoma.
AB - Circular RNAs (circRNAs), a kind of non-coding RNAs, have shown large
capabilities in gene regulation. However, the mechanisms underlying circRNAs
remain largely unknown so far. Recent studies demonstrated that circRNAs play
miRNA sponge effects and regulate gene expression by microRNA response elements.
Here, we screened circRNA expression profiles of bladder carcinoma using
microarray assay. A total of 469 dysregulated circular transcripts are found in
bladder cancer compared with normal tissues, among which 285 were up-regulated
and 184 were down-regulated. Six circRNAs were identified to have significant
differences by qRT-PCR. We speculated that circRNAs might involve in cancer
related pathways via interactions with miRNA by multiple bioinformatical
approaches. Therefore, we further predicted that circTCF25 could sequester miR
103a-3p/miR-107, which potentially lead to the up-regulation of thirteen targets
related to cell proliferation, migration and invasion. Subsequently, we
demonstrated that over-expression of circTCF25 could down-regulate miR-103a-3p
and miR-107, increase CDK6 expression, and promote proliferation and migration in
vitro and vivo. This is the first study to exploit circRNA profiling and
circRNA/miRNA interactions in bladder cancer. Our work laid the foundation to
investigate the functions of circRNAs in cancers. The data also suggest that
circTCF25 might be a new promising marker for bladder cancer.
PMID- 27484178
TI - State-civil society partnerships for HIV/AIDS treatment and prevention in Ghana:
exploring factors associated with successes and challenges.
AB - BACKGROUND: The past decade has seen an increased number of state-civil society
partnerships in the global Human Immunodeficiency Virus/Acquired Immune
Deficiency Syndrome (HIV/AIDS) response of many countries. However, there has
been limited research carried out concerning the successes and challenges of
these partnerships. METHODS: In-depth qualitative interviews were conducted with
23 participants from 21 different state-civil society partnerships throughout
Ghana including all three major geographical zones (Northern, Middle, and
Southern zones) to examine the nature of these partnerships and their positive
and negative effects in responding to the national HIV/AIDS epidemic. RESULTS:
Major themes included: 1) commitment by the government and civil society
organizations to work cooperatively in order to support the development and
implementation of HIV/AIDS interventions in Ghana; 2) the role of civil society
organizations in facilitating community mobilization; capacity building; and
information, resources and skills exchange to increase the efficiency and
effectiveness of these partnerships for HIV prevention and treatment; and 3)
significant challenges including funding issues and other structural barriers for
these partnerships that need to be addressed moving forward. CONCLUSIONS: Future
research should focus on examining the impact of recommended changes on state
civil partnerships and studying the extent and nature of these partnerships in
other countries in order to establish the generalizability of the findings from
this study.
PMID- 27484177
TI - Factors associated with married women's support of male circumcision for HIV
prevention in Uganda: a population based cross-sectional study.
AB - BACKGROUND: Despite the protective effect of male circumcision (MC) against HIV
in men, the acceptance of voluntary MC in priority countries for MC scale-up such
as Uganda remains limited. This study examined the role of women's
sociodemographic characteristics, knowledge of HIV and sexual bargaining power as
determinants of women's support of male circumcision (MC). METHODS: Data from the
Uganda AIDS Indicator Survey, 2011 were analyzed (n = 4,874). Bivariate and
multivariate logistic regression analyses with random intercept were conducted to
identify factors that influence women's support of MC. RESULTS: Overall, 67.0 %
(n = 3,276) of the women in our sample were in support of MC but only 28.0 % had
circumcised partners. Women who had the knowledge that circumcision reduces HIV
risk were about 6 times as likely to support MC than women who lacked that
knowledge [AOR (adjusted odds ratio) = 5.85, 95 % CI (confidence interval) = 4.83
7.10]. The two indicators of women's sexual bargaining power (i.e., ability to
negotiate condom use and ability to refuse sex) were also positively associated
with support of MC. Several sociodemographic factors particularly wealth index
were also positively associated with women's support of MC. CONCLUSIONS: The
findings in this study will potentially inform intervention strategies to enhance
uptake of male circumcision as a strategy to reduce HIV transmission in Uganda.
PMID- 27484179
TI - Grey matter atrophy in prodromal stage of dementia with Lewy bodies and
Alzheimer's disease.
AB - BACKGROUND: Little is known about the patterns of brain atrophy in prodromal
dementia with Lewy bodies (pro-DLB). METHODS: In this study, we used SPM8 with
diffeomorphic anatomical registration through exponentiated lie algebra to
measure grey matter (GM) volume and investigate patterns of GM atrophy in pro-DLB
(n = 28) and prodromal Alzheimer's disease (pro-AD) (n = 27) and compared and
contrasted them with those in elderly control subjects (n = 33) (P <= 0.05
corrected for family-wise error). RESULTS: Patients with pro-DLB showed
diminished GM volumes of bilateral insulae and right anterior cingulate cortex
compared with control subjects. Comparison of GM volume between patients with pro
AD and control subjects showed a more extensive pattern, with volume reductions
in temporal (hippocampi and superior and middle gyri), parietal and frontal
structures in the former. Direct comparison of prodromal groups suggested that
more atrophy was evident in the parietal lobes of patients with pro-AD than
patients with pro-DLB. In patients with pro-DLB, we found that visual
hallucinations were associated with relative atrophy of the left cuneus.
CONCLUSIONS: Atrophy in pro-DLB involves the insulae and anterior cingulate
cortex, regions rich in von Economo neurons, which we speculate may contribute to
the early clinical phenotype of pro-DLB.
PMID- 27484181
TI - The potential role of incorporating real-time PCR and DNA sequencing for
amplification and detection of 16S rRNA gene signatures in neonatal sepsis.
AB - OBJECTIVES: This study aimed to explore whether 16S rRNA gene amplification by
real time PCR and sequencing could serve as genetic-based methods in rapid and
accurate diagnosis of neonatal sepsis. PATIENTS AND METHODS: This case control
study was conducted on 40 neonates suffering from sepsis like manifestations
recruited from the neonatal intensive care unit of Menoufia university hospital
over a period of 6 months. Their blood samples were used for paired analysis of
bacterial growth using BACTEC 9050 instrument and real time PCR assay with
subsequent DNA sequencing for bacterial species identification. RESULTS: The
detection rate of culture proven sepsis was 70%. By using real time 16S r RNA PCR
amplification method, the detection of bacteria was improved to 80%. Real time
PCR revealed sensitivity, specificity, positive predictive value and negative
predictive value of [100%, 66.7%, 87.5% and 100%] respectively. Compared to
culture, the 16S rRNA real time PCR demonstrated a high negative value for ruling
out neonatal sepsis. There was significant statistical difference between the PCR
positive and negative cases as regards the hematological sepsis score. The
results demonstrated the ability of DNA sequencing to recognize 4 pathogens which
were negative by blood culture. The time consumed to detect sepsis using blood
culture was up to 5 days while it took up to 16 h only by PCR and sequencing
methods. CONCLUSION: 16S rRNA gene amplification by real time PCR and sequence
analysis could be served as ideal and reliable genetic-based methods to diagnose
and rule out sepsis with provision of additional data that cannot be obtained by
routine laboratory tests with a shorter turnaround time than those with culture
based protocols.
PMID- 27484180
TI - Vinflunine for the treatment of breast cancer.
AB - INTRODUCTION: Breast cancer is the most frequently diagnosed cancer and the
highest cause of cancer mortality in females worldwide. The development of drugs
improving overall survival in late-stage metastatic breast cancer remains a
challenge. Vinflunine is the most recently developed drug in the vinca alkaloid
class. Its arrival has been eagerly awaited for treatment of solid tumors, and in
particular, for metastatic breast cancer. AREAS COVERED: The pharmacological
features of vinflunine are described. Its clinical development as monotherapy or
in combination in metastatic breast cancer is detailed. A literature search on
the topic was conducted through PubMed, clinical trials and the proceedings of
the main cancer congresses. EXPERT OPINION: The overall results from phase III
studies, and in particular those that combined vinflunine with capecitabine, have
been less favorable. The combination's effectiveness was at best moderate
compared with other drugs which also target metastatic breast cancer, and
complicated by significant hematological and gastrointestinal adverse effects.
Its use in advanced metastatic breast cancer cannot currently be recommended.
PMID- 27484182
TI - Mediastinal chyloma after lung cancer surgery: case report.
AB - BACKGROUND: Chylothorax is a relatively rare but well-known complication of
thoracic surgery. CASE PRESENTATION: A 70-year-old man underwent right upper and
middle bilobectomy and systematic lymph node dissection through a posterolateral
thoracotomy for lung cancer. On the second postoperative day, he developed
chylothorax that was treated with dietary management and pleurodesis. The
discharge diminished and his chest tube was removed on the ninth postoperative
day. On the 14(th) postoperative day, the patient complained of dyspnea and
dysphagia, and imaging studies revealed mediastinal chyloma. Thoracoscopic
surgical drainage was performed and the site of chyle leakage was sutured.
CONCLUSIONS: This report presents an unexpected complication of chemical
pleurodesis and reviews the indications for surgical intervention in cases of
postoperative chylothorax.
PMID- 27484183
TI - Emergent behavior in strongly correlated electron systems.
AB - I describe early work on strongly correlated electron systems (SCES) from the
perspective of a theoretical physicist who, while a participant in their
reductionist top-down beginnings, is now part of the paradigm change to a bottom
up 'emergent' approach with its focus on using phenomenology to find the
organizing principles responsible for their emergent behavior disclosed by
experiment-and only then constructing microscopic models that incorporate these.
After considering the organizing principles responsible for the emergence of
plasmons, quasiparticles, and conventional superconductivity in SCES, I consider
their application to three of SCES's sister systems, the helium liquids, nuclei,
and the nuclear matter found in neutron stars. I note some recent applications of
the random phase approximation and examine briefly the role that paradigm change
is playing in two central problems in our field: understanding the emergence and
subsequent behavior of heavy electrons in Kondo lattice materials; and finding
the mechanism for the unconventional superconductivity found in heavy electron,
organic, cuprate, and iron-based materials.
PMID- 27484184
TI - Factors influencing transitional care from adolescents to young adults with
cancer in Taiwan: A population-based study.
AB - BACKGROUND: To investigate the progress of transition from paediatric to adult
health care for patients with cancer in Taiwan's medical system. METHODS: The
data were retrieved from the Longitudinal Health Insurance Database (LHID), which
contains the original inpatient and outpatient medical claims data for 1,000,000
enrollees randomly sampled from the NHIRD between 1997 and 2010. RESULTS: Among
the 1,411 cancer patients selected for this study, 98.09 % received adult
oriented therapy before the age of 18. In addition, only 1.91 % of the patients
received paediatric-oriented therapy during adolescence. The primary factors that
determine whether these patients would receive paediatric-oriented therapy or
adult-oriented therapy at an early age were as follows: the age of the patient at
the first visit and the performance-level of the hospital (p < 0.001).
CONCLUSIONS: Previous studies conducted in developed countries have demonstrated
that the unwillingness of patients to switch from paediatric-oriented therapy to
adult-oriented therapy being the major obstacle that hinders the transition
process. However, this study revealed a different result: the implementation of
the National Health Insurance system in Taiwan makes healthcare affordable for
the adolescent patients who may not possess adequate knowledge about paediatric
health care and may not appreciate paediatric-oriented therapy, thereby hindering
the transition process.
PMID- 27484185
TI - CHEK2 represses breast stromal fibroblasts and their paracrine tumor-promoting
effects through suppressing SDF-1 and IL-6.
AB - BACKGROUND: Active fibroblasts, the predominant and the most active cells of
breast cancer stroma, are responsible for tumor growth and spread. However, the
molecular mediators and pathways responsible for stromal fibroblast activation,
and their paracrine pro-carcinogenic effects are still not well defined. The
CHEK2 tumor suppressor gene codes for a protein kinase, which plays important
roles in the cellular response to various genotoxic stresses. METHODS:
Immunoblotting, quantitative RT-PCR and Immunofluorescence were used to assess
the expression of CHEK2 in different primary breast fibroblasts and in tissues.
The effect of CHEK2 on the expression and secretion of SDF-1 and IL-6 was
evaluated by immunoblotting and ELISA. The WST-1 colorimetric assay was used to
assess cell proliferation, while the BD BioCoat Matrigel invasion chambers were
utilized to determine the effects of CHEK2 on the migratory and the invasiveness
capacities of breast stromal fibroblasts as well as breast cancer cells. RESULTS:
We have shown that CHEK2 is down-regulated in most cancer-associated fibroblasts
(CAFs) as compared to their corresponding tumor counterpart fibroblasts (TCFs) at
both the mRNA and protein levels. Interestingly, CHEK2 down-regulation using
specific siRNA increased the expression/secretion of both cancer-promoting
cytokines SDF-1 and IL-6, and transdifferentiated stromal fibroblasts to
myofibroblasts. These cells were able to enhance the proliferation of non
cancerous epithelial cells, and also boosted the migration/invasion abilities of
breast cancer cells in a paracrine manner. The later effect was SDF-1/IL-6
dependent. Importantly, ectopic expression of CHEK2 in active CAFs converted
these cells to a normal state, with lower migration/invasion capacities and
reduced paracrine pro-carcinogenic effects. CONCLUSION: These results indicate
that CHEK2 possesses non-cell-autonomous tumor suppressor functions, and present
the Chk2 protein as an important mediator in the functional interplay between
breast carcinomas and their stromal fibroblasts.
PMID- 27484186
TI - Remediation of mercury-polluted soils using artificial wetlands.
AB - Mexico's mercury mining industry is important for economic development, but has
unfortunately contaminated soils due to open-air disposal. This case was seen at
two sites in the municipality of Pinal de Amoles, State of Queretaro, Mexico.
This paper presents an evaluation of mercury dynamics and biogeochemistry in two
soils (mining waste soil) using ex-situ wetlands over 36 weeks. In soils sampled
in two former mines of Pinal de Amoles, initial mercury concentrations were 424
+/- 29 and 433 +/- 12 mg kg-1 in La Lorena and San Jose, former mines,
respectively. Typha latifolia and Phragmites australis were used and 20 reactors
were constructed (with and without plants). The reactors were weekly amended with
a nutrient solution (NPK), for each plant, at a pH of 5.0. For remediation using
soils from San Jose 70-78% of mercury was removed in T. latifolia reactors and 76
82% in P. australis reactors, and for remediation of soils from La Lorena,
mercury content was reduced by 55-71% using T. latifolia and 58-66% in P.
australis reactors. Mercury emissions into the atmosphere were estimated to be 2
4 mg m-2 h-1 for both soils.
PMID- 27484188
TI - Advanced Mitigation Process (AMP) for Improving Laser Damage Threshold of Fused
Silica Optics.
AB - The laser damage precursors in subsurface of fused silica (e.g. photosensitive
impurities, scratches and redeposited silica compounds) were mitigated by mineral
acid leaching and HF etching with multi-frequency ultrasonic agitation,
respectively. The comparison of scratches morphology after static etching and
high-frequency ultrasonic agitation etching was devoted in our case. And
comparison of laser induce damage resistance of scratched and non-scratched fused
silica surfaces after HF etching with high-frequency ultrasonic agitation were
also investigated in this study. The global laser induce damage resistance was
increased significantly after the laser damage precursors were mitigated in this
case. The redeposition of reaction produce was avoided by involving multi
frequency ultrasonic and chemical leaching process. These methods made the
increase of laser damage threshold more stable. In addition, there is no scratch
related damage initiations found on the samples which were treated by Advanced
Mitigation Process.
PMID- 27484187
TI - Ruling out nosocomial transmission of Cryptosporidium in a renal transplantation
unit: case report.
AB - BACKGROUND: Cryptosporidium spp. is a ubiquitous parasite affecting humans as
well as domestic and wild vertebrates, causing diarrhea in both immunocompetent
and immunocompromised hosts worldwide. Its transmission occurs primarily by the
fecal-oral route. In humans, C. parvum and C. hominis are the most prevalent
species, whereas immunocompetent and immunocompromised individuals can also be
infected by other zoonotic species. Renal transplant patients are prone to
develop cryptosporidiosis, which can induce severe and life-threatening diarrhea.
CASE PRESENTATION: We report here a series of nearly concomitant cases of acute
symptomatic cryptosporidiosis in three renal transplant patients attending the
Strasbourg University Hospital Nephrology Unit. The clinical presentation was
persistent diarrhea and acute renal failure. The diagnosis was confirmed by
microscopic stool examination using a modified Ziehl-Neelsen staining method and
species identification by molecular tools. All patients were treated with
nitazoxanide and recovered from diarrhea after 14 days of therapy. CONCLUSION:
Genotypic species identification was not consistent with an epidemic context,
thus underlining the need for genotyping to monitor at risk patients.
PMID- 27484189
TI - The Value of Mitotic Count and Ki67 Proliferation Index in Congenital Mesoblastic
Nephroma.
AB - OBJECTIVE: We aimed to define the histopathologic features and proliferative rate
of congenital mesoblastic nephroma (CMN) as a risk factor for recurrence.
METHODS: Fourteen cases of CMN among 138 registered pediatric renal tumors were
retrospectively reviewed. The prognostic impact for mitotic rate and Ki67 index
was investigated. RESULTS: There were four (28.6%) classic, six (42.9%) cellular,
and four (28.6%) mixed type CMNs, with average Ki-67 counts of 16.75% in the
classic CMN, and 53.2% in the tumors with cellular components (both mixed and
cellular CMNs). Twelve patients (85.7%) were aged less than six months. Tumors
with cellular component showed significantly larger tumor diameter and higher Ki
67 index (p = 0.015 and p = 0.016, respectively). The patient with cellular CMN,
whose tumor showed the highest mitotic rate (4.9/HPF), but not the highest Ki67
index (57.4%), died of recurrent disease with distant metastasis. CONCLUSION:
Proliferative markers-mitotic count and Ki67 index-have limited value to predict
recurrence or metastasis in CMNs with a cellular component.
PMID- 27484192
TI - Abstracts of the 51st Workshop for Pediatric Research.
PMID- 27484190
TI - Innate lymphoid cells: models of plasticity for immune homeostasis and rapid
responsiveness in protection.
AB - Innate lymphoid cells (ILCs) have stormed onto the immune landscape as "newly
discovered" cell types. These tissue-resident sentinels are enriched at mucosal
surfaces and engage in complex cross talk with elements of the adaptive immune
system and microenvironment to orchestrate immune homeostasis. Many parallels
exist between innate cells and T cells leading to the initial partitioning of
ILCs into rather rigid subsets that reflect their "adaptive-like" effector
cytokines profiles. ILCs themselves, however, have unique attributes that are
only just beginning to be elucidated. These features result in complementarity
with, rather than complete duplication of, functions of the adaptive immune
system. Key transcription factors determine the pathway of differentiation of
progenitors towards an ILC1, ILC2, or ILC3 subset. Once formed, flexibility in
the responses of these subsets to stimuli unexpectedly allows transdifferentation
between the different subsets and the acquisition of altered phenotypes and
function. This provides a mechanism for rapid innate immune responsiveness. Here,
we discuss the models of differentiation for maintenance and activation of tissue
resident ILCs in maintaining immune homeostasis and protection.
PMID- 27484191
TI - #Vapelife: An Exploratory Study of Electronic Cigarette Use and Promotion on
Instagram.
AB - BACKGROUND: The growth of social networking services has enabled the sharing of
electronic cigarette opinions and experiences via user-generated content.
OBJECTIVES: This exploratory study analyzed electronic cigarette content found on
the visual social networking service, Instagram, in order to highlight public
health challenges created by this content and support understanding of electronic
cigarette promotion and usage. METHODS: A qualitative content analysis was
performed on Instagram posts made with the hashtags #ecig or #vape in October
2014. Images, text, and hashtags from 85 posts (43 #ecig, 42 #vape) were
analyzed. In addition, the total number of posts made with eight key electronic
cigarette hashtags was recorded at four points between March 2014 and October
2015. RESULTS: The total number of #vape posts on Instagram grew by 4,163,274
during the study period, while #ecig posts increased by 741,916. Of the posts
examined in-depth, corporate users made up over half of posts. No posts were
critical of electronic cigarettes. Few mentioned electronic cigarettes in the
context of health benefits. No posts included major brands, and mod style
electronic cigarettes were mentioned or depicted in over half of posts. A
majority of posts included hashtags expressing vaping identity and community. In
addition, users mentioned novel practices such as sub-ohming.
Conclusions/Importance: Instagram users in our sample characterized electronic
cigarettes primarily as novel devices rather than equivalents to cigarettes.
Further, hashtag communities and identities appear to be forming around vaping.
Future research should consider the public health implications of these hashtags,
as well as novel electronic cigarette practices.
PMID- 27484194
TI - Prevalence and assessment of traumatic brain injury in prison inmates: A
systematic PRISMA review.
AB - OBJECTIVES: The primary objectives of the present systematic PRISMA review were:
(1) to explore the range of prevalence of TBI in offenders and whether this is
higher than in a control sample; (2) to determine which screening measures are
available and evaluate the evidence on these; and, lastly, (3) to evaluate
whether prevalence of TBI is associated with increased prevalence of other health
conditions and/or offending behaviour. METHODS: The present systematic PRISMA
review explores the peer-reviewed literature published since 2005 which has
investigated TBI in incarcerated populations using five databases (CINAHL,
MEDLINE, PsycARTICLES, Psychology and Behavioral Sciences Collection, PsycINFO)
in addition to separate searches conducted on 'Google Scholar' using specific
search criteria. RESULTS: Seventeen studies were identified which explored the
prevalence of TBI in inmates. Only five of the seventeen studies which
investigated prevalence of TBI in offender populations looked at juvenile
offending. Interestingly, only seven of the 17 studies included both male and
female samples (two of which did not report findings separately for males and
females). In terms of the assessments used to investigate prevalence, three
studies investigated the prevalence of TBI using The Ohio State University (OSU)
TBI Identification method (OSU-TBI-ID). Nine studies used one or two questions in
order to elicit information on whether the offender had previously experienced a
TBI. Only two studies used the Traumatic Brain Injury Questionnaire (TBIQ). One
study used the Brain Injury Screening Index (BISI). One study investigated
patients discharged from non-federal South Carolina Emergency Departments or
hospitals with a TBI-related ICD-9-CM code. Lastly evidence of TBI checklist from
medical record (14 items) was used in one study. CONCLUSIONS: In terms of the
implication for further research and practice, the studies identified in this
review clearly emphasize the need to account for TBI in managing care in offender
populations, which may contribute to reduction in offending behaviours.
Additionally, there is a need for further research investigating the clinical
utility of screening tools for detecting TBI in offender populations such as The
Traumatic Brain Injury Questionnaire (TBIQ), The Brain Injury Screening Index
(BISI) and The Ohio State University (OSU-TBI-ID) TBI Identification method.
PMID- 27484193
TI - Endocannabinoid system: Role in depression, reward and pain control (Review).
AB - Depression and pain co-exist in almost 80% of patients and are associated with
impaired health-related quality of life, often contributing to high mortality.
However, the majority of patients who suffer from the comorbid depression and
pain are not responsive to pharmacological treatments that address either pain or
depression, making this comorbidity disorder a heavy burden on patients and
society. In ancient times, this depression-pain comorbidity was treated using
extracts of the Cannabis sativa plant, known now as marijuana and the mode of
action of Delta9-tetrahydrocannabinol, the active cannabinoid ingredient of
marijuana, has only recently become known, with the identification of cannabinoid
receptor type 1 (CB1) and CB2. Subsequent investigations led to the
identification of endocannabinoids, anandamide and 2-arachidonoylglycerol, which
exert cannabinomimetic effects through the CB1 and CB2 receptors, which are
located on presynaptic membranes in the central nervous system and in peripheral
tissues, respectively. These endocannabinoids are produced from membrane lipids
and are lipohilic molecules that are synthesized on demand and are eliminated
rapidly after their usage by hydrolyzing enzymes. Clinical studies revealed
altered endocannabinoid signaling in patients with chronic pain. Considerable
evidence suggested the involvement of the endocannabinoid system in eliciting
potent effects on neurotransmission, neuroendocrine, and inflammatory processes,
which are known to be deranged in depression and chronic pain. Several synthetic
cannabinomimetic drugs are being developed to treat pain and depression. However,
the precise mode of action of endocannabinoids on different targets in the body
and whether their effects on pain and depression follow the same or different
pathways, remains to be determined.
PMID- 27484195
TI - Muscleblind-like 3 deficit results in a spectrum of age-associated pathologies
observed in myotonic dystrophy.
AB - Myotonic dystrophy type I (DM1) exhibits distinctive disease specific phenotypes
and the accelerated onset of a spectrum of age-associated pathologies. In DM1,
dominant effects of expanded CUG repeats result in part from the inactivation of
the muscleblind-like (MBNL) proteins. To test the role of MBNL3, we deleted Mbnl3
exon 2 (Mbnl3(DeltaE2)) in mice and examined the onset of age-associated diseases
over 4 to 13 months of age. Accelerated onset of glucose intolerance with
elevated insulin levels, cardiac systole deficits, left ventricle hypertrophy, a
predictor of a later onset of heart failure and the development of subcapsular
and cortical cataracts is observed in Mbnl3(DeltaE2) mice. Retention of embryonic
splice isoforms in adult organs, a prominent defect in DM1, is not observed in
multiple RNAs including the Insulin Receptor (Insr), Cardiac Troponin T (Tnnt2),
Lim Domain Binding 3 (Ldb3) RNAs in Mbnl3(DeltaE2) mice. Although rare DM1-like
splice errors underlying the observed phenotypes cannot be excluded, our data in
conjunction with the reported absence of alternative splice errors in embryonic
muscles of a similar Mbnl3(DeltaE2) mouse by RNA-seq studies, suggest that
mechanisms distinct from the adult retention of embryonic splice patterns may
make important contributions to the onset of age-associated pathologies in DM1.
PMID- 27484196
TI - iLIR database: A web resource for LIR motif-containing proteins in eukaryotes.
AB - Atg8-family proteins are the best-studied proteins of the core autophagic
machinery. They are essential for the elongation and closure of the phagophore
into a proper autophagosome. Moreover, Atg8-family proteins are associated with
the phagophore from the initiation of the autophagic process to, or just prior
to, the fusion between autophagosomes with lysosomes. In addition to their
implication in autophagosome biogenesis, they are crucial for selective autophagy
through their ability to interact with selective autophagy receptor proteins
necessary for the specific targeting of substrates for autophagic degradation. In
the past few years it has been revealed that Atg8-interacting proteins include
not only receptors but also components of the core autophagic machinery, proteins
associated with vesicles and their transport, and specific proteins that are
selectively degraded by autophagy. Atg8-interacting proteins contain a short
linear LC3-interacting region/LC3 recognition sequence/Atg8-interacting motif
(LIR/LRS/AIM) motif which is responsible for their interaction with Atg8-family
proteins. These proteins are referred to as LIR-containing proteins (LIRCPs). So
far, many experimental efforts have been carried out to identify new LIRCPs,
leading to the characterization of some of them in the past 10 years. Given the
need for the identification of LIRCPs in various organisms, we developed the iLIR
database ( https://ilir.warwick.ac.uk ) as a freely available web resource,
listing all the putative canonical LIRCPs identified in silico in the proteomes
of 8 model organisms using the iLIR server, combined with a Gene Ontology (GO)
term analysis. Additionally, a curated text-mining analysis of the literature
permitted us to identify novel putative LICRPs in mammals that have not
previously been associated with autophagy.
PMID- 27484198
TI - Innate heart regeneration: endogenous cellular sources and exogenous therapeutic
amplification.
AB - INTRODUCTION: The -once viewed as heretical- concept of the adult mammalian heart
as a dynamic organ capable of endogenous regeneration has recently gained
traction. However, estimated rates of myocyte turnover vary wildly and the
underlying mechanisms of cardiac plasticity remain controversial. It is still
unclear whether the adult mammalian heart gives birth to new myocytes through
proliferation of resident myocytes, through cardiomyogenic differentiation of
endogenous progenitors or through both mechanisms. AREAS COVERED: In this review,
the authors discuss the cellular origins of postnatal mammalian cardiomyogenesis
and touch upon therapeutic strategies that could potentially amplify innate
cardiac regeneration. EXPERT OPINION: The adult mammalian heart harbors a limited
but detectable capacity for spontaneous endogenous regeneration. During normal
aging, proliferation of pre-existing cardiomyocytes is the dominant mechanism for
generation of new cardiomyocytes. Following myocardial injury, myocyte
proliferation increases modestly, but differentiation of endogenous progenitor
cells appears to also contribute to cardiomyogenesis (although agreement on the
latter point is not universal). Since cardiomyocyte deficiency underlies almost
all types of heart disease, development of therapeutic strategies that amplify
endogenous regeneration to a clinically-meaningful degree is of utmost
importance.
PMID- 27484197
TI - Reversible lysine acetylation is involved in DNA replication initiation by
regulating activities of initiator DnaA in Escherichia coli.
AB - The regulation of chromosomal replication is critical and the activation of DnaA
by ATP binding is a key step in replication initiation. However, it remains
unclear whether and how the process of ATP-binding to DnaA is regulated. Here, we
show that DnaA can be acetylated, and its acetylation level varies with cell
growth and correlates with DNA replication initiation frequencies in E. coli.
Specifically, the conserved K178 in Walker A motif of DnaA can be acetylated and
its acetylation level reaches the summit at the stationary phase, which prevents
DnaA from binding to ATP or oriC and leads to inhibition of DNA replication
initiation. The deacetylation process of DnaA is catalyzed by deacetylase CobB.
The acetylation process of DnaA is mediated by acetyltransferase YfiQ, and
nonenzymatically by acetyl-phosphate. These findings suggest that the reversible
acetylation of DnaA ensures cells to respond promptly to environmental changes.
Since Walker A motif is universally distributed across organisms, acetylation of
Walker A motif may present a novel regulatory mechanism conserved from bacteria
to eukaryotes.
PMID- 27484199
TI - Impact of literacy and years of education on the diagnosis of dementia: A
population-based study.
AB - BACKGROUND: The effect of different educational indices on clinical diagnosis of
dementia requires more investigation. OBJECTIVE: We compared the differential
influence of two educational indices (EIs): years of schooling and level of
education (i.e., null/low literacy, can read and write, primary school, and
secondary school) on global cognition, functional performance, and the
probability of having a dementia diagnosis. METHOD: A total of 3,816 participants
were selected from the population-based study of older adults "Neurological
Disorders in Central Spain" (NEDICES). The 37-item version of the Mini-Mental
State Examination (MMSE-37) and the Pfeffer's questionnaire were applied to
assess cognitive and functional performance, respectively. The diagnosis of
dementia was performed by expert neurologists according to Diagnostic and
Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria. Logistic
regression models adjusted for potential confounders were carried out to test the
association between the two EIs and dementia diagnosis. RESULTS: Both EIs were
significantly associated with cognitive and functional scores, but individuals
with null/low literacy performed significantly worse on MMSE-37 than literates
when these groups were compared in terms of years of schooling. The two EIs were
also related to an increased probability of dementia diagnosis in logistic
models, but the association's strength was stronger for level of education than
for years of schooling. CONCLUSION: Literacy predicted cognitive performance over
and above the years of schooling. Lower education increases the probability of
having a dementia diagnosis but the impact of different EIs is not uniform.
PMID- 27484200
TI - Leaching of PAHs from agricultural soils treated with oil shale combustion ash:
an experimental study.
AB - The present study focuses on the fate of polycyclic aromatic hydrocarbons (PAHs)
in soils amended with oil shale ash (OSA). Leachability studies to assess the
release of PAHs to the environment are essential before the application of OSA in
agriculture. A quantitative estimation of the leaching of PAHs from two types of
soil and two types of OSA was undertaken in this study. Two leaching approaches
were chosen: (1) a traditional one step leaching scheme and (2) a leaching scheme
with pretreatment, i.e.., incubation of the material in wet conditions imitating
the field conditions, followed by a traditional leaching procedure keeping the
total amount of water constant. The total amount of PAHs leached from soil/OSA
mixtures was in the range of 15 to 48 MUg/kg. The amount of total PAHs leached
was higher for the incubation method, compared to the traditional leaching
method, particularly for Podzolic Gleysols soil. This suggests that for the
incubation method, the content of organic matter and clay minerals of the soil
influence the fate of PAHs more strongly compared to the traditional leaching
scheme. The amount of PAHs leached from OSA samples is higher than from soil/OSA
mixtures, which suggests soils to inhibit the release of PAHs. Calculated amount
of PAHs from experimental soil and OSA leaching experiments differed considerably
from real values. Thus, it is not possible to estimate the amount of PAHs leached
from soil/OSA mixtures based on the knowledge of the amount of PAHs leached from
soil and OSA samples separately.
PMID- 27484201
TI - Residue decline and risk assessment of fluopyram + tebuconazole (400SC) in/on
onion (Allium cepa).
AB - A method was validated for estimating fluopyram and tebuconazole in onion on LC
MS/MS using dispersive QuEChERS. Three sprays of a combination fungicide
fluopyram + tebuconazole (Luna experience, 400 SC) were applied @ 75 + 75 and 150
+ 150 g a.i. ha-1 at an interval of 10 days on onion using Knapsack sprayer.
First spray was made at bulb setting stage. Spring onion samples were drawn at 0
(1 h), 1, 3, 5, 7, 10, 15, and 20 days and matured onion bulb at harvest (52
days) after the last spray. Soil samples were also drawn at harvest. Foliar
application of the combination product resulted in 1.14 and 2.86 mg kg-1
fluopyram residues on spring onion at standard and double dose, respectively, one
hour after the last application. The levels of fluopyram residues gradually
declined and recorded 0.25 and 0.58 mg kg-1 on 20th day of application with half
lives of 8.8 and 9.1 days at standard and double dose, respectively. For
tebuconazole, the corresponding residues observed after 1 h (0 day) of
application were 0.92 and 2.29 mg kg-1. The levels declined gradually to 0.12 and
0.33 mg kg-1 on 20th days with half-life of 6.7 to 7.7 days at standard and
double dose, respectively. Here, we are proposing a pre-harvest interval of 7 day
for fluopyram and tebuconazole in spring onion when applied at 75 + 75 g a.i. ha
1 (400 SC). Risk assessment was done by calculating hazard quotient and by
comparing theoretical maximum residue intake (TMRI) with maximum permissible
intake (MPI). In all the cases, results of the study showed that HQ (Hazard
Quotient) <=1 and TMDI < MPI. Hence, the use of this combination product can be
recommended with pre harvest interval of 7 days. The data can be used in
establishing MRLs (maximum residue limits) for spring onion after considering
multilocation trials.
PMID- 27484203
TI - Strategies for bioengineered scaffolds that support adipose stem cells in
regenerative therapies.
AB - Regenerative medicine possesses the potential to ameliorate damage to tissue that
results from a vast range of conditions, including traumatic injury, tumor
resection and inherited tissue defects. Adult stem cells, while more limited in
their potential than pluripotent stem cells, are still capable of differentiating
into numerous lineages and provide feasible allogeneic and autologous treatment
options for many conditions. Adipose stem cells are one of the most abundant
types of stem cell in the adult human. Here, we review recent advances in the
development of synthetic scaffolding systems used in concert with adipose stem
cells and assess their potential use for clinical applications.
PMID- 27484202
TI - Heavy metals in tissues of scorpionfish (Scorpaena porcus) caught from Black Sea
(Turkey) and potential risks to human health.
AB - Scorpionfish (Scorpaena porcus) is a demersal fish species commercially important
for its of which meat is tough and delicious. The aim of this study was to
determine heavy metal (Al, Cu, Ni, As, Cd, Hg, Pb, U) concentrations in this fish
species which is traditionally consumed in the Black Sea Area and, to compare the
concentrations of various toxic elements in different organs of the fish
specimens (muscle, liver, gill, and skin). Within this scope, the mineralization
was performed using microwave digestion system. Thirty-two scorpionfish caught
from Sinop Inland Port during 2010 were analyzed. The heavy metal concentrations
were determined with the method of inductively coupled plasma mass spectroscopy
(ICP-MS). Verification of the method was demonstrated by analysis of standard
reference material (NRCC-TORT-2 lobster hepatopancreas). After evaluation of the
results, it was determined that the highest heavy metal accumulation was
generally found in the liver. The maximum aluminum level and the minimum uranium
level were found in the analyzed tissues. In terms of heavy metals, Al, Cu, Cd,
and Hg showed a statistically significant difference between tissues (p < 0.05).
It was determined that heavy metal concentrations obtained from the muscle
tissues did not exceed the national and international recommended limits; and
also it was found that daily intake amounts did not exceed tolerable daily intake
amounts. Furthermore, in THQ based risk evaluation, the value 1 which is crucial
for children and adults was not surpassed. In terms of public health, it was
found out that there was not any risk in consumption of scorpionfish in the study
area.
PMID- 27484204
TI - Impact of tumor histology and grade on treatment success of percutaneous renal
cryoablation.
AB - BACKGROUND: We analyzed oncological outcomes in patients who underwent
percutaneous renal cryoablation (PRC) with documented renal cell carcinoma (RCC)
by perioperative biopsy. METHODS: Multicenter retrospective analysis of 153
patients [median follow-up 48 months] who underwent PRC from 09/2005 to 08/2014
was performed. We divided the cohort into patients who developed recurrence
versus no recurrence. Kaplan-Meier analyses examined recurrence-free survival
(RFS) according to grade and histology. Multivariable analysis (MVA) was
performed to identify factors associated with tumor recurrence. RESULTS: One
hundred and fifty-three patients were analyzed [18 patients (11.8 %) with
recurrence and 135 (88.2 %) patients without recurrence]. There were no
differences between the groups with respect to demographics, RENAL score, and
number of probes utilized. Recurrence group had larger tumor size (3.1 vs. 2.4
cm; p = 0.011), upper pole tumor location (p = 0.016), and greater proportions of
high-grade tumor (33 vs. 0.7 %; p < 0.001) and clear cell histology (77.8 vs.
45.9 %; p = 0.011). Four-year RFS was 100 versus 80 % for grade 1 versus grade
2/3 tumors (p = 0.0002), and 97 versus 88 % for other RCC versus clear cell RCC
(p = 0.07). MVA demonstrated tumor size >3 cm (OR 2.46; p = 0.019), clear cell
histology (OR 2.12; p = 0.027), and high tumor grade (OR 2.33, p < 0.001) as
independent risk factors associated with tumor recurrence. CONCLUSIONS:
Association of higher grade and clear cell histology with recurrence and
progression suggests need for increased emphasis on preoperative risk
stratification by biopsy, with grade 1 and non-clear cell RCC being associated
with improved treatment success than higher grade and clear cell RCC.
PMID- 27484205
TI - Neural supply of the male urethral sphincter: comprehensive anatomical review and
implications for continence recovery after radical prostatectomy.
AB - PURPOSE: To review the anatomical facts of urethral sphincter (US) innervation
discovered over the last three decades and to determine the implications for
continence recovery after radical prostatectomy (RP). METHODS: Using the
PubMed(r) database, we searched for peer-reviewed articles in English between
January 1985 and September 2015, with the following terms: 'urethral sphincter,'
'urethral rhabdosphincter,' 'urinary continence and nerve supply' and
'neuroanatomy and nerve sparing.' The anatomical methodology, number of bodies
examined, data, figures, relevant facts and text were analyzed. RESULTS:
Seventeen articles on 254 anatomical subjects were reviewed. Coexisting pathways
were described in every article. Dissection, histology, simulation or electron
microscopy evidence supported arguments for somatic and autonomic pathways. From
the most to the least substantiated, somatic sphincteric fibers were described
extra- or intrapelvic as: direct from the distal pudendal nerve (PuN), recurrent
from the dorsal nerve of the penis, from the proximal PuN with an intrapelvic
course, extrapudendal somatic fibers dispersed among autonomic pelvic fibers.
From the pelvic plexus, or from the neurovascular bundles, autonomic fibers to
the US have been described in 13 of the reviewed articles, with at least each of
the available anatomical methods. CONCLUSION: Because continence depends on a
number of factors, it is challenging to delineate the specific impact of
periprostatic nerve sparing on continence, but the anatomical data suggest that
RP surgeons should steer toward the preservation and protection of these nerves
whenever possible.
PMID- 27484206
TI - Future directions in prostate cancer testing: a comment upon results from the
prospective population-based diagnostic STHLM3 study-Gronberg H et al. Lancet
Oncology. 2015 Nov 9; doi:10.1016/S1470-2045(15)00361-7.
PMID- 27484207
TI - Early Childhood Environment and Genetic Interactions: the Diathesis for Suicidal
Behavior.
AB - Adverse childhood experiences are associated with higher risk for suicide and
suicidal behavior later in life. There are known associations between childhood
trauma, particularly sexual abuse, and higher rates of suicide, non-lethal
suicide attempts, and non-suicidal self-injurious behaviors in adolescence and
adulthood. Emotional abuse/neglect, disrupted parental attachment, and cumulative
effect of multiple forms of maltreatment, also increase risk. Yet, the causal
relationship remains unclear. The diathesis-stress model provides a framework for
understanding how early life adverse experiences contribute to suicide
vulnerability. Current findings from the fields of biology, neurology, and
genetics shed new light on mediating variables and possible causal links between
early childhood trauma and suicide. In this paper, we review recent advances,
particularly regarding the interaction of early life environmental adverse events
with genetics factors, that increase the diathesis for psychological traits are
associated with subsequent deliberate self-harm behaviors.
PMID- 27484208
TI - miR-22-5p revealed as a potential biomarker involved in the acute phase of
myocardial infarction via profiling of circulating microRNAs.
AB - Acute myocardial infarction (AMI) is a life-threatening episode of coronary
artery disease. Recently, circulating myocardial-derived microRNAs (miRNAs) have
been reported as potential biomarkers of infarction. The present study aimed to
identify differentially expressed miRNAs in patients with ST-segment elevation
myocardial infarction that could be potentially dysregulated in response to early
myocardial damage. miRNA expression profile analysis was performed using the
Serum/Plasma Focus miRNA Polymerase Chain Reaction (PCR) panel of Exiqon A/S
(Vedbaek, Denmark) on plasma samples of patients on the first day of AMI
(admission) and on samples from the identical patients collected six months
following AMI. Selected miRNAs were validated by reverse transcription
quantitative PCR (RT-qPCR) using independent patients with AMI and a control
group of patients with a stable coronary artery disease. Thirty-two species of
plasma miRNA were differentially expressed (P<0.05) on admission compared with
six months following AMI. Subsequent validation in an independent patient group
confirmed that miR-133b and miR-22-5p were significantly up-regulated in the
serum of patients with AMI. The receiver operating characteristic (ROC) curve
analysis demonstrated a diagnostic utility for miR-22-5p, which has not
previously been reported to be associated with AMI. Among the selected miRNAs,
miR-22-5p represents a novel promising biomarker for the diagnosis of AMI.
PMID- 27484209
TI - Factors influencing the health-related quality of life of Chinese advanced cancer
patients and their spousal caregivers: a cross-sectional study.
AB - BACKGROUND: Cancer and its treatment have a major impact on the lives of patients
and their intimate partners, such as on their health-related quality of life
(HRQOL). The aims of this study are to: (i) assess the HRQOL of advanced cancer
patients and spousal caregivers, and explore the relationship between the HRQOL
of cancer patients and that of their spousal caregivers; (ii) detect factors
influencing the HRQOL of cancer patients and spousal caregivers; and (iii)
explore the impact of anxiety and depression on the HRQOL of couples. METHODS: A
total of 131 couples where one of the partners was hospitalized for advanced
cancer were invited to complete a survey to assess their demographic and
background information, HRQOL, and anxiety and depression. HRQOL was measured
using the SF-12, while anxiety and depression were measured using the Hospital
Anxiety and Depression Scale. Data were analyzed using a T-test, Pearson
correlations, multiple linear regressions, and structural equation modeling.
RESULTS: In general, the spousal caregivers had higher levels of HRQOL (seven out
of eight SF-12 domains and two SF-12 dimensions) p = 0.038-0.000, anxiety (p =
0.002), and depression (p = 0.011) than patients. Correlations of HRQOL between
patients and spouses were small to moderate (r = 0.193-0.398). Multiple
independent factors influencing the physical component summary (PCS), mental
component summary (MCS), vitality (VT), and role emotional (RE) sections of the
SF-12 were identified, including: gender, time since diagnosis, levels of
education, working status, the extent to which spousal caregivers were informed
about the disease, improved marital relationship after the diagnosis of cancer,
and anxiety and depression. For both patients and spousal caregivers, the
strongest independent factor influencing HRQOL (SF-12 PCS, MCS, VT, and RE) was
anxiety and depression. Anxiety and depression may have both actor and partner
effects on the HRQOL of couples to various degrees. CONCLUSIONS: The findings of
this study call attention to the HRQOL of couples and its influencing factors.
Individual characteristics of cancer patients and spouses, marital relationship,
and anxiety and depression are highlighted as areas in which couples coping with
cancer could benefit from interventions to improve their HRQOL.
PMID- 27484210
TI - mTOR is a fine tuning molecule in CDK inhibitors-induced distinct cell death
mechanisms via PI3K/AKT/mTOR signaling axis in prostate cancer cells.
AB - Purvalanol and roscovitine are cyclin dependent kinase (CDK) inhibitors that
induce cell cycle arrest and apoptosis in various cancer cells. We further
hypothesized that co-treatment of CDK inhibitors with rapamycin, an mTOR
inhibitor, would be an effective combinatory strategy for the inhibition of
prostate cancer regard to androgen receptor (AR) status due to inhibition of
proliferative pathway, PI3K/AKT/mTOR, and induction of cell death mechanisms.
Androgen responsive (AR+), PTEN(-/-) LNCaP and androgen independent (AR-),
PTEN(+/-) DU145 prostate cancer cells were exposed to purvalanol (20 uM) and
roscovitine (30 uM) with or without rapamycin for 24 h. Cell viability assay,
immunoblotting, flow cytometry and fluorescence microscopy was used to define the
effect of CDK inhibitors with or without rapamycin on proliferative pathway and
cell death mechanisms in LNCaP and DU145 prostate cancer cells. Co-treatment of
rapamycin modulated CDK inhibitors-induced cytotoxicity and apoptosis that CDK
inhibitors were more potent to induce cell death in AR (+) LNCaP cells than AR (
) DU145 cells. CDK inhibitors in the presence or absence of rapamycin induced
cell death via modulating upstream PI3K/AKT/mTOR signaling pathway in LNCaP
cells, exclusively only treatment of purvalanol have strong potential to inhibit
both upstream and downstream targets of mTOR in LNCaP and DU145 cells. However,
co-treatment of rapamycin with CDK inhibitors protects DU145 cells from apoptosis
via induction of autophagy mechanism. We confirmed that purvalanol and
roscovitine were strong apoptotic and autophagy inducers that based on regulation
of PI3K/AKT/mTOR signaling pathway. Co-treatment of rapamycin with purvalanol and
roscovitine exerted different effects on cell survival and death mechanisms in
LNCaP and DU145 cell due to their AR receptor status. Our studies show that co
treatment of rapamycin with CDK inhibitors inhibit prostate cancer cell viability
more effectively than either agent alone, in part, by targeting the mTOR
signaling cascade in AR (+) LNCaP cells. In this point, mTOR is a fine-tuning
player in purvalanol and roscovitine-induced apoptosis and autophagy via
regulation of PI3K/AKT and the downstream targets, which related with cell
proliferation.
PMID- 27484211
TI - Inhibition of autophagy by chloroquine induces apoptosis in primary effusion
lymphoma in vitro and in vivo through induction of endoplasmic reticulum stress.
AB - Autophagy plays a crucial role in cancer cell survival and the inhibition of
autophagy is attracting attention as an emerging strategy for the treatment of
cancer. Chloroquine (CQ) is an anti-malarial drug, and is also known as an
inhibitor of autophagy. Recently, it has been found that CQ induces cancer cell
death through the inhibition of autophagy; however, the underlying mechanism is
not entirely understood. In this study, we identified the role of CQ-induced
cancer cell death using Primary Effusion Lymphoma (PEL) cells. We found that a CQ
treatment induced caspase-dependent apoptosis in vitro. CQ also suppressed PEL
cell growth in a PEL xenograft mouse model. We showed that CQ activated
endoplasmic reticulum (ER) stress signal pathways and induced CHOP, which is an
inducer of apoptosis. CQ-induced cell death was significantly decreased by
salbrinal, an ER stress inhibitor, indicating that CQ-induced apoptosis in PEL
cells depended on ER stress. We show here for the first time that the inhibition
of autophagy induces ER stress-mediated apoptosis in PEL cells. Thus, the
inhibition of autophagy is a novel strategy for cancer chemotherapy.
PMID- 27484212
TI - "Heart failure, whole-body insulin resistance and myocardial insulin resistance:
An intriguing puzzle".
PMID- 27484213
TI - Conducting and interpreting high-quality systematic reviews and meta-analyses.
AB - Systematic reviews and meta-analyses are powerful tools for summarizing existing
literature and combining evidence from multiple studies. These methods employ
complex searches, statistical techniques, and presentation techniques with which
the clinical audience may not be very familiar. This review article aims to
familiarize the clinical audience with the various techniques employed to conduct
a high-quality systematic review and meta-analysis.
PMID- 27484214
TI - Prospective evaluation of shape similarity based pose prediction method in D3R
Grand Challenge 2015.
AB - Evaluation of ligand three-dimensional (3D) shape similarity is one of the
commonly used approaches to identify ligands similar to one or more known active
compounds from a library of small molecules. Apart from using ligand shape
similarity as a virtual screening tool, its role in pose prediction and pose
scoring has also been reported. We have recently developed a method that utilizes
ligand 3D shape similarity with known crystallographic ligands to predict binding
poses of query ligands. Here, we report the prospective evaluation of our pose
prediction method through the participation in drug design data resource (D3R)
Grand Challenge 2015. Our pose prediction method was used to predict binding
poses of heat shock protein 90 (HSP90) and mitogen activated protein kinase
kinase kinase kinase (MAP4K4) ligands and it was able to predict the pose within
2 A root mean square deviation (RMSD) either as the top pose or among the best of
five poses in a majority of cases. Specifically for HSP90 protein, a median RMSD
of 0.73 and 0.68 A was obtained for the top and the best of five predictions
respectively. For MAP4K4 target, although the median RMSD for our top prediction
was only 2.87 A but the median RMSD of 1.67 A for the best of five predictions
was well within the limit for successful prediction. Furthermore, the performance
of our pose prediction method for HSP90 and MAP4K4 ligands was always among the
top five groups. Particularly, for MAP4K4 protein our pose prediction method was
ranked number one both in terms of mean and median RMSD when the best of five
predictions were considered. Overall, our D3R Grand Challenge 2015 results
demonstrated that ligand 3D shape similarity with the crystal ligand is
sufficient to predict binding poses of new ligands with acceptable accuracy.
PMID- 27484216
TI - Moms and Media: Exploring the Effects of Online Communication on Infant Feeding
Practices.
AB - Using a survey of mothers with young children (N = 455), this study applies
Fishbein and Ajzen's reasoned action approach (RAA) to examine the relationship
between online communication and infant feeding practices. Contrary to
expectations, attitudes, perceived normative pressure, and perceived behavioral
control (PBC) did not fully mediate the relationship between time spent online
and behavioral intentions. Our findings indicate a significant, direct, negative
association between time spent online and breastfeeding intentions In this
article, theoretical and practical implications for health communication are
discussed.
PMID- 27484215
TI - Hydrogen polysulfide (H2S n ) signaling along with hydrogen sulfide (H2S) and
nitric oxide (NO).
AB - Hydrogen sulfide (H2S) is a physiological mediator with various roles, including
neuro-modulation, vascular tone regulation, and cytoprotection against ischemia
reperfusion injury, angiogenesis, and oxygen sensing. Hydrogen polysulfide (H2S n
), which possesses a higher number of sulfur atoms than H2S, recently emerged as
a potential signaling molecule that regulates the activity of ion channels, a
tumor suppressor, transcription factors, and protein kinases. Some of the
previously reported effects of H2S are now attributed to the more potent H2S n .
H2S n is produced by 3-mercaptopyruvate sulfurtransferase (3MST) from 3
mercaptopyruvate (3MP) and is generated by the chemical interaction of H2S with
nitric oxide (NO). H2S n sulfhydrates (sulfurates) cysteine residues of target
proteins and modifies their activity, whereas H2S sulfurates oxidized cysteine
residues as well as reduces cysteine disulfide bonds. This review focuses on the
recent progress made in studies concerning the production and physiological roles
of H2S n and H2S.
PMID- 27484217
TI - The incidence and mortality of major cancers in China, 2012.
AB - BACKGROUND: The National Central Cancer Registry (NCCR) collected population
based cancer registration data in 2012 from local registries and estimated the
cancer incidence and mortality in China. METHODS: In the middle of 2015, 261
cancer registries submitted reports on new cancer cases and deaths occurred in
2012. Qualified data from 193 registries were used for analysis after evaluation.
Crude rates, number of cases, and age-standardized rates stratified by area
(urban/rural), sex, age group, and cancer type were calculated according to the
national population in 2012. RESULTS: The covered population were 198,060,406
from 193 qualified cancer registries (74 urban and 119 rural registries). The
major indicators of quality control, percentage of cases morphologically verified
(MV%), death certificate-only cases (DCO%), and the mortality to incidence (M/I)
ratio, were 69.13%, 2.38%, and 0.62, respectively. It was estimated that there
were 3,586,200 new cancer cases and 2,186,600 cancer deaths in 2012 in China with
an incidence of 264.85/100,000 [age-standardized rate of incidence by the Chinese
standard population (ASRIC) of 191.89/100,000] and a mortality of 161.49/100,000
[age-standardized rate of mortality by the Chinese standard population (ASRMC) of
112.34/100,000]. The ten most common cancer sites were the lung, stomach, liver,
colorectum, esophagus, female breast, thyroid, cervix, brain, and pancreas,
accounting for approximately 77.4% of all new cancer cases. The ten leading
causes of cancer death were lung cancer, liver cancer, gastric cancer, esophageal
cancer, colorectal cancer, pancreatic cancer, female breast cancer, brain tumor,
leukemia, and lymphoma, accounting for 84.5% of all cancer deaths. CONCLUSIONS:
Continuous cancer registry data provides basic information in cancer control
programs. The cancer burden in China is gradually increasing, both in urban and
rural areas, in males and females. Efficient cancer prevention and control, such
as health education, tobacco control, and cancer screening, should be paid
attention by the health sector and the whole society of China.
PMID- 27484218
TI - Synthesis and characterization of a Bi10O8(OAr)16 oxo-cluster supported by p-tert
butylcalix[5]arene ligands.
AB - Reaction of a non-dried monobenzylated [(t)BuC5(OBn)(OH)4] ligand with excess of
Bi[N(SiMe3)2]3 yields a mixture of the dimeric complex 1 [Bi{(t)BuC5(OBn)(OH)}]2
in 12% yield and complex 2 [Bi10O8{(t)BuC5(OBn)(OH)}4] in 48% yield. The highly
symmetric complex 2 features a Bi10O8(OAr)16 central core with tetra-, hexa- and
heptacoordinated bismuth(iii) centers, and (MU2)-(MU4) bridging oxygen atoms all
arranged in a I4 symmetrical pattern. Cluster 2 represents the largest bismuth
oxo-cluster supported by calix[n]arene ligands reported to date.
PMID- 27484219
TI - Thyroid Function Variations Within the Reference Range Do Not Affect Quality of
Life, Mood, or Cognitive Function in Community-Dwelling Older Men.
AB - BACKGROUND: Variations in thyroid function within the laboratory reference range
have been associated with a number of clinical outcomes. However, quality of
life, mood, and cognitive function have not been extensively studied, and it is
not clear whether mild variations in thyroid function have major effects on these
neurocognitive outcomes. METHODS: Data were analyzed from the Osteoporotic
Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years
and older in the United States. A total of 539 participants who were not taking
thyroid medications and had age-adjusted TSH levels within the reference range
underwent detailed testing of quality of life, mood, and cognitive function at
baseline. The same quality of life, mood, and cognitive outcomes were measured
again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed
using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent
variables, adjusting for relevant covariates. RESULTS: At baseline, there were no
associations between TSH or FT4 levels and measures of quality of life, mood, or
cognition in the 539 euthyroid men. Baseline thyroid function did not predict
changes in these outcomes over a mean of 6 years in the 193 men in the
longitudinal analysis. CONCLUSIONS: Variations in thyroid function within the age
adjusted laboratory reference range are not associated with variations in quality
of life, mood, or cognitive function in community-dwelling older men.
PMID- 27484220
TI - Identification and analysis of copine/BONZAI proteins among evolutionarily
diverse plant species.
AB - Copines are evolutionarily conserved calcium-dependent membrane-binding proteins
with potentially critical biological functions. In plants, the function of these
proteins has not been analyzed except for in Arabidopsis thaliana where they play
critical roles in development and disease resistance. To facilitate functional
studies of copine proteins in crop plants, genome-wide identification, curation,
and phylogeny analysis of copines in 16 selected plant species were conducted.
All the identified 32 plant copines have conserved features of the two C2 domains
(C2A and C2B) and the von Willebrand factor A (vWA) domain. Different from animal
and protozoa copines, plant copines have glycine at the second residue
potentially acquiring a unique protein myristoylation modification. Phylogenetic
analysis suggests that copine was present as one copy when evolving from green
algae to basal flowering plants, and duplicated before the divergence of monocots
and dicots. In addition, gene expression and protein localization study of rice
copines suggests both conserved and different properties of copines in dicots and
monocots. This study will contribute to uncovering the role of copine genes in
different plant species.
PMID- 27484221
TI - Mycobacterium tuberculosis H37 Rv1222: structural insight in transcription
inhibition.
PMID- 27484222
TI - Ru-Containing Magnetically Recoverable Catalysts: A Sustainable Pathway from
Cellulose to Ethylene and Propylene Glycols.
AB - Biomass processing to value-added chemicals and biofuels received considerable
attention due to the renewable nature of the precursors. Here, we report the
development of Ru-containing magnetically recoverable catalysts for cellulose
hydrogenolysis to low alcohols, ethylene glycol (EG) and propylene glycol (PG).
The catalysts are synthesized by incorporation of magnetite nanoparticles (NPs)
in mesoporous silica pores followed by formation of 2 nm Ru NPs. The latter are
obtained by thermal decomposition of ruthenium acetylacetonate in the pores. The
catalysts showed excellent activities and selectivities at 100% cellulose
conversion, exceeding those for the commercial Ru/C. High selectivities as well
as activities are attributed to the influence of Fe3O4 on the Ru(0)/Ru(4+) NPs. A
facile synthetic protocol, easy magnetic separation, and stability of the
catalyst performance after magnetic recovery make these catalysts promising for
industrial applications.
PMID- 27484223
TI - Boronic acid based imprinted electrochemical sensor for rutin recognition and
detection.
AB - Multi-walled carbon nanotubes (MWNTs) and boronic acid based molecular imprinting
polymer (MIP) were successively modified on a glassy carbon electrode surface to
fabricate a novel electrochemical sensor for rutin recognition and detection. 3
Aminophenylboronic acid (APBA) was chosen as a monomer for the
electropolymerization of MIP film in the presence of rutin. In addition to the
imprinted cavities in MIP film to complement the template molecule in shape and
functional groups, the high affinity between the boronic acid group of APBA and
vicinal diols of rutin also enhanced the selectivity of the sensor, which made
the sensor display a good selectivity to rutin. Moreover, the modified MWNTs
improved the sensitivity of the sensor for rutin detection. The mole ratios of
rutin and APBA, electropolymerized scan cycles and rates, and pH value of the
detection solution were optimized. Under optimal conditions, the sensor was used
to detect rutin in a linear range from 4.0 * 10-7 to 1.0 * 10-5 mol L-1 with a
detection limit of 1.1 * 10-7 mol L-1. The sensor has also been applied to assay
rutin in tablets with satisfactory results.
PMID- 27484224
TI - Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): safety and
efficacy of low-dose prostacyclin administration and blood pressure target in
addition to standard therapy, as compared to standard therapy alone, in post
cardiac arrest syndrome patients: study protocol for a randomized controlled
trial.
AB - BACKGROUND: Morbidity and mortality following initial survival of cardiac arrest
remain high despite great efforts to improve resuscitation techniques and post
resuscitation care, in part due to the ischemia-reperfusion injury secondary to
the restoration of the blood circulation. Patients resuscitated from cardiac
arrest display evidence of endothelial injury and coagulopathy
(hypocoagulability, hyperfibrinolysis), which in associated with poor outcome.
Recent randomized controlled trials have revealed that treatment with infusion of
prostacyclin reduces endothelial damage after major surgery and AMI. Thus, a
study is pertinent to investigate if prostacyclin infusion as a therapeutic
intervention reduces endothelial damage without compromising, or even improving,
the hemostatic competence in resuscitated cardiac arrest patients. Post-cardiac
arrest patients frequently have a need for vasopressor therapy (catecholamines)
to achieve the guideline-supported blood pressure goals. To evaluate a possible
catecholamine interaction with the primary endpoints of this study, included
patients will be randomized into two different blood pressure goals within
guideline-recommended targets. METHODS/DESIGN: A randomized, placebo-controlled,
double-blind investigator-initiated pilot trial in 40 out-of-hospital-cardiac
arrest (OHCA) patients will be conducted. Patients will be randomly assigned to
either the active treatment group (48 hours of active study drug (iloprost, 1
ng/kg/min) or to the control group [placebo (saline) infusion]. Target mean blood
pressure levels will be allocated 1:1 to 65 mmHg or approximately 75 mmHg, which
gives four different permutations, namely: (i) iloprost/65 mHg, (ii) iloprost/75
mmHg, (iii) placebo/65 mmHg, and (iv) placebo/75 mmHg. All randomized patients
will be treated in accordance with state-of-the art therapy including targeted
temperature management. The primary endpoint of this study is change in
biomarkers indicative of endothelial activation and damage, [soluble
thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial
growth factor (sVEGF), nucleosomes] and sympathoadrenal over activation
(epinephrine/norepinephrine) from baseline to 48 hours post-randomization. The
secondary endpoints of this trial will include: (1) the hemostatic profile
[change in functional hemostatic blood test (thrombelastography (TEG) and whole
blood platelet aggregometry (multiplate)) blood cell and endothelial cell-derived
microparticles]; (2) feasibility of blood pressure target intervention (target 90
%); (3) interaction of primary endpoints and blood pressure target; (4) levels of
neuron-specific enolase at 48 hours post-inclusion according to blood pressure
targets. DISCUSSION: The ENDO-RCA study is a pilot study trial that investigates
safety and efficacy of low-dose infusion of prostacyclin administration as
compared to standard therapy in post-cardiac arrest syndrome patients. TRIAL
REGISTRATION: Trial registration at ClinicalTrials.gov (identifier NCT02685618 )
on 18 February 2016.
PMID- 27484225
TI - Does molecular analysis increase the efficacy of bronchoalveolar lavage in the
diagnosis and management of respiratory infections in hemato-oncological
patients?
AB - OBJECTIVES: The identification of the specific pathogen responsible for a
respiratory infection in patients with hematological malignancies (HM) would
ensure relevant treatment and prevent toxicity associated with anti-infective
therapy. This large-scale study aimed to explore the clinical impact of
fiberoptic bronchoscopy with bronchoalveolar lavage (FOB-BAL) in conjunction with
molecular analysis on the diagnosis and management of respiratory infections in
hemato-oncological patients. METHODS: All consecutive patients with HM and
pulmonary infiltrates, who underwent FOB-BAL between January 2008 and January
2013, were included in the analysis. Clinical characteristics, FOB-BAL results,
and treatment adjustments were recorded, and factors predicting a positive BAL
were assessed. RESULTS: Four hundred and twenty-five FOB-BAL procedures were
analyzed. BAL revealed a specific diagnosis in 219 (51.5%) patients, 208 of them
with a pulmonary infection. Infectious etiological agents found were mainly
Aspergillus spp (n=142), bacterial species (n=44), and Pneumocystis jirovecii
(n=34). Multivariate analysis showed that a lymphoproliferative disease, >=2
symptoms (dyspnea/cough/hemoptysis/pleuritic pain), and less than 4 days between
symptom appearance and FOB-BAL, predicted a positive FOB-BAL result. BAL results
prompted a treatment modification in 48% of subjects. CONCLUSIONS: FOB-BAL in
conjunction with molecular assays is efficient in the rapid detection of life
threatening infections, allowing for adjustment of anti-infective therapy, which
may result in better outcomes and reduce treatment-related toxicity.
PMID- 27484226
TI - Gtpbp2 is a positive regulator of Wnt signaling and maintains low levels of the
Wnt negative regulator Axin.
AB - BACKGROUND: Canonical Wnt signals, transduced by stabilized beta-catenin, play
similar roles across animals in maintaining stem cell pluripotency, regulating
cell differentiation, and instructing normal embryonic development. Dysregulated
Wnt/beta-catenin signaling causes diseases and birth defects, and a variety of
regulatory processes control this pathway to ensure its proper function and
integration with other signaling systems. We previously identified GTP-binding
protein 2 (Gtpbp2) as a novel regulator of BMP signaling, however further
exploration revealed that Gtpbp2 can also affect Wnt signaling, which is a novel
finding reported here. RESULTS: Knockdown of Gtpbp2 in Xenopus embryos causes
severe axial defects and reduces expression of Spemann-Mangold organizer genes.
Gtpbp2 knockdown blocks responses to ectopic Wnt8 ligand, such as organizer gene
induction in ectodermal tissue explants and induction of secondary axes in whole
embryos. However, organizer gene induction by ectopic Nodal2 is unaffected by
Gtpbp2 knockdown. Epistasis tests, conducted by activating Wnt signal
transduction at sequential points in the canonical pathway, demonstrate that
Gtpbp2 is required downstream of Dishevelled and Gsk3beta but upstream of beta
catenin, which is similar to the previously reported effects of Axin1
overexpression in Xenopus embryos. Focusing on Axin in Xenopus embryos, we find
that knockdown of Gtpbp2 elevates endogenous or exogenous Axin protein levels.
Furthermore, Gtpbp2 fusion proteins co-localize with Dishevelled and co
immunoprecipitate with Axin and Gsk3b. CONCLUSIONS: We conclude that Gtpbp2 is
required for canonical Wnt/beta-catenin signaling in Xenopus embryos. Our data
suggest a model in which Gtpbp2 suppresses the accumulation of Axin protein, a
rate-limiting component of the beta-catenin destruction complex, such that Axin
protein levels negatively correlate with Gtpbp2 levels. This model is supported
by the similarity of our Gtpbp2-Wnt epistasis results and previously reported
effects of Axin overexpression, the physical interactions of Gtpbp2 with Axin,
and the correlation between elevated Axin protein levels and lost Wnt
responsiveness upon Gtpbp2 knockdown. A wide variety of cancer-causing Wnt
pathway mutations require low Axin levels, so development of Gtpbp2 inhibitors
may provide a new therapeutic strategy to elevate Axin and suppress aberrant beta
catenin signaling in cancer and other Wnt-related diseases.
PMID- 27484227
TI - Dexmedetomidine-ketamine versus Dexmedetomidine-midazolam-fentanyl for monitored
anesthesia care during chemoport insertion: a Prospective Randomized Study.
AB - BACKGROUND: Dexmedetomidine as a sole agent showed limited use for painful
procedures due to its insufficient sedative/analgesic effect, pronounced
hemodynamic instability and prolonged recovery. The aim of this study was to
compare the effects of dexmedetomidine-ketamine (DK) versus dexmedetomidine
midazolam-fentanyl (DMF) combination on the quality of sedation/analgesia and
recovery profiles for monitored anesthesia care (MAC). METHODS: Fifty six
patients undergoing chemoport insertion were randomly assigned to group DK or
DMF. All patients received 1 MUg.kg(-1) dexmedetomidine over 10 min followed by
0.2-1.0 MUg.kg(-1)h(-1) in order to maintain 3 or 4 of modified Observer's
Assessment of Analgesia and Sedation score checked every 3 min. At the start of
dexmedetomidine infusion, patients in group DK or DMF received 0.5 mg.kg(-1)
ketamine or 0.05 mg.kg(-1) midazolam + 0.5 MUg.kg(-1) fentanyl intravenously,
respectively. When required, rescue sedatives (0.5 mg.kg-1 of ketamine or 0.05
mg.kg-1 of midazolam) and analgesics (0.5 mg.kg-1 of ketamine or 0.5 MUg.kg-1 of
fentanyl) were given to the patients in DK or DMF group, respectively. The
primary outcome of this study was the recovery parameters (time to spontaneous
eye opening and the length of the recovery room stay). The secondary outcomes
were parameters indicating quality of sedation/analgesia, cardiorespiratory
variables, and satisfaction scores. RESULTS: There were no significant
differences in the onset time, time to spontaneous eye opening, recovery room
stay, the incidences of inadequate analgesia, hypotension and bradycardia between
the two groups. Despite lower infusion rate of dexmedetomidine, more patients in
the DMF group had bispectral index (BIS) < 60 than in the DK group and vice versa
for need of rescue sedatives. The satisfaction scores of patients, surgeon, and
anesthesiologist in the DMF group were significantly better than the DK group.
CONCLUSIONS: The DK and DMF groups showed comparable recovery time, onset time,
cardiorespiratory variables, and analgesia. However, the DMF group showed a
better sedation quality and satisfaction scores despite the lower infusion rate
of dexmedetomidine, and a higher incidence of BIS < 60 than the DK group. TRIAL
REGISTRATION: Clinical Trial Registry of Korea KCT0000951 , registered
12/12/2013.
PMID- 27484228
TI - Ovarian Stimulation, Intrauterine Insemination, Multiple Pregnancy and Major
Congenital Malformations: A Systematic Review and Meta- Analysis- The ART_Rev
Study.
AB - INTRODUCTION: Multiple pregnancies are a recognized adverse effect of assisted
reproductive technologies; nevertheless, there is no consensus on the incremental
risk associated with the ovarian stimulation (OS) used alone and intrauterine
insemination (IUI). The relationship between OS and IUI and the risk of major
congenital malformations (MCM) is unclear. OBJECTIVE: To summarise the literature
and evaluate the risk of multiple pregnancy and MCM associated with OS used alone
and IUI used with or without OS compared to natural conception (spontaneously
conceived infants without any type of fertility treatments). METHODS: We carried
out a systematic review to identify published papers between 1966 and 2014 in
MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. We
included observational studies and randomized clinical trials related to the risk
of multiple pregnancies and MCM conceived following OS alone or IUI compared to
natural conception (spontaneously conceived infants without any fertility
treatments). The quality of the included studies was evaluated using The Cochrane
Collaboration's tool for assessing risk of bias for RCTs and the Newcastle-Ottawa
Scale for observational studies. RESULTS: There were 63 studies included in this
review. Our systematic review suggests that the use of any OS alone was
associated with an increased risk of multiple pregnancy compared to natural
conception (pooled RR 8.80, 95% CI 5.09- 15.20; p= 0.000; 9 studies). Similar
increases in the risk of multiple pregnancies were observed following clomiphene
citrate used without assisted reproductive technologies. Compared to natural
conception, the use of IUI with or without OS was associated with an increased
risk of multiple pregnancy (pooled RR 9.73, 95% CI 7.52 -12.60; p= 0.000; 6
studies). Compared to natural conception, the use of any OS alone was associated
with an increased risk of any MCM (RR pooled 1.18, 95%CI 1.03-1.36; 11 studies),
major musculoskeletal malformations (pooled RR 1.48, 95%CI 1.21-1.81; 7 studies),
and malformations of the nervous system (pooled RR 1.73, 95%CI 1.15-2.61; 6
studies). Compared to natural conception, the use of IUI was associated with an
increased risk of any MCM (pooled RR 1.23, 95%CI 1.10-1.37; 10 studies), major
urogenital (pooled RR 1.52, 95%CI 1.04-2.22; 7 studies), and musculoskeletal
malformations (pooled RR 1.54, 95%CI 1.20-1.98; 7 studies). The overall quality
of the included studies was acceptable. CONCLUSIONS: The increased risk of
multiple pregnancy and certain types of MCM associated with the use of less
invasive fertility treatments, such as OS and IUI, found in this review,
highlights the importance of the practice framing. Heterogeneity in OS protocols,
the combination with other fertility agents, the limited number of studies and
the methodological quality differences reduce our ability to draw conclusions on
specific treatment. More observational studies, assessing the risk of multiple
pregnancy or MCM, as a primary outcome, using standardized methodologies, in
larger and better clinically defined populations are needed.
PMID- 27484229
TI - Geniculate Ganglion Tumors: Clinical Presentation and Surgical Results.
AB - OBJECTIVE: Facial nerve tumors are rare lesions mostly located in the geniculate
ganglion. This study aims to compare those tumors limited to the geniculate
ganglion in terms of clinical features and postoperative outcomes. STUDY DESIGN:
Case series with chart review. SETTINGS: University tertiary reference center.
SUBJECTS AND METHODS: Medical charts were reviewed for 17 patients who had
surgery for geniculate ganglion tumor removal (10 hemangiomas, 6 schwannomas, 1
meningioma). Hemangiomas and schwannomas were compared for preoperative facial
nerve function, hearing, tumor size, and postoperative outcomes. RESULTS: Facial
palsy was observed in all cases. Regarding the preoperative facial nerve
function, severe facial palsy (House-Brackmann grades V and VI) was present in
70% of cases for hemangiomas and for no case of schwannoma (P = .01), although
hemangiomas were significantly smaller tumors (P = .01). Hearing loss was
observed in 4 cases (23.5%) and was related to tumor volume (P < .0001). A
complete excision was achieved in all cases, and a facial nerve graft was
performed immediately after interruption in 16 patients (94%). Postoperative
facial nerve function was improved or stabilized in 94% of cases. A preoperative
House-Brackman grade VI was shown as a negative factor for postoperative facial
nerve function. CONCLUSIONS: Differences in clinical presentations could help in
establishing the good therapeutic option depending on the tumor type. Surgery,
when indicated, is safe and effective, and postoperative outcomes are not related
to tumor type.
PMID- 27484230
TI - Predicting Outcomes after Uvulopalatopharyngoplasty for Adult Obstructive Sleep
Apnea: A Meta-analysis.
AB - OBJECTIVE: Uvulopalatopharyngoplasty (UPPP) remains one of the most common
surgical treatments for patients with obstructive sleep apnea. However, the
results after UPPP are unpredictable. The purpose of this meta-analysis is to
identify predictors of success after UPPP. DATA SOURCES: A literature search was
performed utilizing PubMed, EMBASE, SCOPUS, and the Cochrane Library. REVIEW
METHODS: The keywords and medical subject heading terms used were
uvulopalatopharyngoplasty and UPPP. Studies were included if UPPP was used as a
single surgical procedure for the treatment of obstructive sleep apnea and
results were presented separately as responder (surgical success) and
nonresponder (surgical failure). Exclusion criteria included pediatric patients
and other surgical procedures (eg, nasal and hypopharyngeal) performed at the
same time as the UPPP. Age, body mass index, preoperative apnea-hypopnea index,
Friedman stage, and several cephalometric variables were compared between
responders and nonresponders. RESULTS: A total of 1257 studies were screened,
with 15 studies included in this meta-analysis. Our results demonstrate that
Friedman stage I is a strong predictor for success after UPPP, while Friedman
stage III and low hyoid position are negative predictors. Age, body mass index,
preoperative apnea-hypopnea index, and other cephalometric measurements were not
significant. CONCLUSION: Friedman stage and hyoid position are important
predictors for UPPP.
PMID- 27484231
TI - Laryngeal Verrucous Carcinoma.
AB - Objective Laryngeal verrucous carcinoma (LVC) is a rare, locally invasive
neoplasm comprising 1% to 3.4% of laryngeal carcinomas. Management strategies are
a topic of ongoing conversation, and no definitive treatment protocol based on T
stage and presentation exists. This review examines characteristics, treatment
modalities, and patient outcomes of LVC. Data Sources PubMed, MEDLINE, EMBASE,
and Web of Science. Methods Databases were searched through October 29, 2015, for
literature detailing individual patient cases of LVC. Variables analyzed included
patient demographics, tumor characteristics, tumor size, treatment, and outcomes.
Results Thirty-seven articles with 369 cases were included. LVC was found more
commonly in males (13.8:1), at an average age of 58.7 years, and located in the
glottis (74.0%). Most patients had local disease at presentation (94.9%). The
most common presenting symptom was hoarseness (92.3%). The most common primary
treatment was surgery alone (72.3%), with local excision as the most common
technique (56.8%). In patients with data available on both surgical modality and
T stage, most patients who presented as T1 and were managed surgically underwent
local excision (79.2%). Surgical treatment alone led to high rates of disease
free survival at follow-up (86.8%). A large number of patients presenting with T1
disease were disease free at follow-up (88.6%). Overall survival was 80.3%.
Conclusion LVC is most often managed surgically. The extent of surgical resection
may be guided by T stage, with smaller tumors resected via local excision and
larger tumors via partial or total laryngectomy. Regardless of T stage or
therapy, LVC has a good posttreatment prognosis.
PMID- 27484232
TI - Laryngeal, Retropharyngeal, and Cervical Glomangiopericytomas: A Case Report.
PMID- 27484233
TI - Therapeutic Mastoidectomy in the Management of Noncholesteatomatous Chronic
Otitis Media: Literature Review and Cost Analysis.
AB - OBJECTIVE: Despite evidence that therapeutic mastoidectomy does not improve
outcomes in noncholesteatomatous chronic otitis media, it remains widely
performed. An up-to-date systematic review is undertaken and conclusions drawn
regarding the best evidence-based practice of its management. DATA SOURCES:
PubMed, Google Scholar, Medline Embase, Cochrane, and Web of Science. REVIEW
METHOD: A combination of the following words was used: chronic otitis media,
chronic suppurative otitis media, COM, CSOM, mastoidectomy, tympanoplasty,
atelectasis, retraction, tympanic perforation, and therapeutic. RESULTS: From
1742 studies, 7 were selected for full analysis with respect to the benefit of
mastoidectomy in the management of active and inactive mucosal chronic otitis
media. Most were retrospective studies, with 1 prospective randomized controlled
trial available. Overall, there was no evidence to support routine mastoidectomy
in conjunction with tympanoplasty in chronic otitis media. For ears with
sclerotic mastoids, the evidence suggested that there may be some benefit as a
staged procedure. Two studies were analyzed for the benefit of mastoidectomy in
addition to tympanoplasty for the management of the atelectatic ear (inactive
squamous chronic otitis media). The conclusion was also that mastoidectomy added
no benefit. CONCLUSIONS: Examination of the available literature supports the
notion that therapeutic mastoidectomy does not lend any additional benefit to the
management of noncholesteatomatous chronic otitis media. This has implications
for patient care, both clinically and financially. Further research, ideally in
the form of a prospective, multi-institutional, geographically wide, ethnically
diverse, randomized controlled trial, is needed to further support this notion.
PMID- 27484234
TI - Perceptual Assessment of Velopharyngeal Dysfunction by Otolaryngology Residents.
AB - OBJECTIVE: To assess the ability of otolaryngology residents to rate the
hypernasal resonance of patients with velopharyngeal dysfunction. We hypothesize
that experience (postgraduate year [PGY] level) and training will result in
improved ratings of speech samples. STUDY DESIGN: Prospective cohort study.
SETTING: Otolaryngology training programs at 2 academic medical centers. SUBJECTS
AND METHODS: Thirty otolaryngology residents (PGY 1-5) were enrolled in the
study. All residents rated 30 speech samples at 2 separate times. Half the
residents completed a training module between the rating exercises, with the
other half serving as a control group. Percentage agreement with the expert
rating of each speech sample and intrarater reliability were calculated for each
resident. Analysis of covariance was used to model accuracy at session 2.
RESULTS: The median percentage agreement at session 1 was 53.3% for all
residents. At the second session, the median scores were 53.3% for the control
group and 60% for the training group, but this difference was not statistically
significant. Intrarater reliability was moderate for both groups. Residents were
more accurate in their ratings of normal and severely hypernasal speech. There
was no correlation between rating accuracy and PGY level. Score at session 1
positively correlated with score at session 2. CONCLUSION: Perceptual training of
otolaryngology residents has the potential to improve their ratings of hypernasal
speech. Length of time in residency may not be best predictor of perceptual
skill. Training modalities incorporating practice with hypernasal speech samples
could improve rater skills and should be studied more extensively.
PMID- 27484235
TI - Discharge Destination after Head and Neck Surgery: Predictors of Discharge to
Postacute Care.
AB - OBJECTIVE: In recent decades, there has been a reduction in the length of
postoperative hospital stay, with a corresponding increase in discharge to
postacute care. Discharge to postacute care facilities represents a meaningful
patient-centered outcome; however, little has been published about this outcome
after head and neck surgery. STUDY DESIGN: Retrospective review of national
database. SETTING: American College of Surgeons National Surgical Quality
Improvement Program from 2011 to 2013. SUBJECTS AND METHODS: We compared the rate
of discharge to home versus postacute care facilities in patients admitted after
head and neck surgery and used multivariable logistic regression to identify
predictors of discharge to postacute care. RESULTS: The overall rate of discharge
to postacute care facilities after head and neck surgery (n = 15,890) was 15.7%
after major surgery (including laryngectomy, composite resection, and free tissue
transfer), 4.4% after moderate surgery (including regional tissue transfer,
oropharyngeal or oral cavity resection, and neck dissection), and 1.1% after
minor head and neck surgery (including endocrine or salivary gland surgery). On
multivariable analysis, significant preoperative predictors of discharge to
postacute care were advanced age, functional status, major or moderate surgical
procedures, tracheostomy, advanced American Society of Anesthesiologists class,
low body mass index, and dyspnea. CONCLUSION: Our study indicates that patients
undergoing major or moderate head and neck surgery, patients with reduced
functional status, and patients with advanced comorbidities are at substantial
risk of discharge to postacute care. The possibility of discharge to postacute
care should be discussed with high-risk patients.
PMID- 27484236
TI - Bimodal Stimulation in Prelingually Deaf Children: Lessons from a Cross-sectional
Survey.
AB - OBJECTIVE: (1) To survey the use of bimodal stimulation by prelingually deaf
children receiving unilateral cochlear implantation and (2) to investigate
demographic and audiologic factors explaining the use of bimodal stimulation.
STUDY DESIGN: Cross-sectional survey. SETTING: Tertiary care institution.
SUBJECTS AND METHODS: The study included 44 unilaterally implanted prelingually
deaf children from a single institution, with a minimum follow-up of 1 year.
During routine follow-up visits, an examiner interviewed parents on their
children's use of bimodal stimulation. At the same time, residual hearing and
hearing aid gain in the contralateral ear were assessed. RESULTS: Approximately
half of patients (52%) used bimodal stimulation. On average, bimodal users showed
better mean unaided and aided thresholds than nonbimodal users (P < .001). A mean
250- to 500-Hz unaided threshold <=90 dB HL in the contralateral, nonimplanted
ear was associated with a higher probability of bimodal use (P = .008). Parental
satisfaction with the contralateral hearing aid was inversely correlated with
mean 125- to 500-Hz and 1000- to 4000-Hz unaided thresholds (P < .001) and mean
250- to 500-Hz and 1000- to 4000-Hz aided thresholds (P < .001). CONCLUSIONS: A
mean 250- to 500-Hz unaided threshold <=90 dB HL is associated with a higher
probability of bimodal use by prelingually deaf children. Better residual hearing
is associated with a higher degree of parental satisfaction with the
contralateral hearing aid. This information could be useful to counsel parents of
prelingually deaf children, when deciding between bimodal stimulation and
simultaneous bilateral cochlear implantation.
PMID- 27484238
TI - Mild Camurati-Engelamann disease presenting with exophthalmos as the first and
only manifestation: A case report.
AB - Camurati-Engelmann disease (CED; MIM 131300), or progressive diaphyseal
dysplasia, is a rare autosomal dominant bone disease, which is caused by
mutations in the transforming growth factor-beta1 (TGFbeta1) gene on chromosome
19q13.1-13.3. Extremely variable penetrance has been reported to be associated
with CED, the most common features of which are limb pain, waddling gait and
muscle weakness. The present study reported on a consanguineous Chinese family
with one affected individual that initially presented with exophthalmos, which
has not previously been reported as an initial manifestation of CED. The proband
was a 22-year-old woman that presented with progressive proptosis. Except for
increased serum levels of alkaline phosphatase and C-terminal telopeptide of type
I collagen, no other biochemical abnormalities were detected. Whole-body
radiological and bone scintigraphic investigations revealed that hyperostosis and
sclerosis predominantly affected the cranial bones, including the skull base, and
only mildly affected the long bones. A heterozygous mutation involving a G to A
transition at the cDNA position +653 of TGFbeta1 was detected in the patient
only, but not in her family members, by automated DNA sequencing using an ABI DNA
sequencer (Model 377). Based on the clinical, biochemical, radiological and
genetic findings, a diagnosis of CED was confirmed. Considering the phenotypic
variability associated with CED and the unique manifestations of the patient
described in the present study, CED should be taken into account regarding the
differential diagnosis of exophthalmos.
PMID- 27484237
TI - Genetic and Environmental Determinants of Otitis Media in an Indigenous Filipino
Population.
AB - OBJECTIVE: To identify genetic and environmental risk factors for otitis media in
an indigenous Filipino population. STUDY DESIGN: Cross-sectional study. SETTING:
Indigenous Filipino community. SUBJECTS AND METHODS: Clinical history and
information on breastfeeding, tobacco smoke exposure, and swimming were obtained
from community members. Heads of households were interviewed for family history
and personal beliefs on ear health. Height and weight were measured. Otoscopic
findings were described for the presence and character of perforation or
discharge. An A2ML1 duplication variant that confers otitis media susceptibility
was Sanger sequenced in all DNA samples. Co-occurrence of middle ear bacteria
detected by 16S rRNA gene sequencing was determined according to A2ML1 genotype
and social cluster. RESULTS: The indigenous Filipino population has a ~50%
prevalence of otitis media. Young age was associated with otitis media (4 age
strata; P = .004); however, age was nonsignificant as a bistratal or continuous
variable. There was no association between otitis media and sex, body mass index,
breastfeeding, tobacco exposure, or deep swimming. In multivariate analyses,
A2ML1 genotype is the strongest predictor of otitis media, with an odds ratio of
3.7 (95% confidence interval: 1.3-10.8; P = .005). When otitis media diagnoses
were plotted across ages, otitis media was observed within the first year of
life, and chronic otitis media persisted up to adulthood, particularly in A2ML1
variant carriers. CONCLUSION: Among indigenous Filipinos, A2ML1 genotype is the
primary risk factor for otitis media and main determinant of disease progression,
although age, the middle ear microbiome, and social clusters might modulate the
effect of the A2ML1 genotype.
PMID- 27484240
TI - Copper-Catalyzed N-Arylation of 2-Pyridones Employing Diaryliodonium Salts at
Room Temperature.
AB - A new and mild synthetic approach for the N-arylation of 2-pyridones with
diaryliodonium salts has been developed. Most reactions proceed readily at room
temperature in the presence of 10 mol % of copper chloride. As a result, a wide
range of N-arylpyridine-2-ones were synthesized in yields of 23% to 99%. With
this method, an antifibrotic drug, Pirfenidone, was successfully synthesized in
99% yield within 30 min at room temperature.
PMID- 27484239
TI - Real-time imaging of Huntingtin aggregates diverting target search and gene
transcription.
AB - The presumptive altered dynamics of transient molecular interactions in vivo
contributing to neurodegenerative diseases have remained elusive. Here, using
single-molecule localization microscopy, we show that disease-inducing Huntingtin
(mHtt) protein fragments display three distinct dynamic states in living cells -
1) fast diffusion, 2) dynamic clustering and 3) stable aggregation. Large, stable
aggregates of mHtt exclude chromatin and form 'sticky' decoy traps that impede
target search processes of key regulators involved in neurological disorders.
Functional domain mapping based on super-resolution imaging reveals an unexpected
role of aromatic amino acids in promoting protein-mHtt aggregate interactions.
Genome-wide expression analysis and numerical simulation experiments suggest mHtt
aggregates reduce transcription factor target site sampling frequency and impair
critical gene expression programs in striatal neurons. Together, our results
provide insights into how mHtt dynamically forms aggregates and disrupts the
finely-balanced gene control mechanisms in neuronal cells.
PMID- 27484241
TI - Statin-induced myopathy in a usual care setting-a prospective observational study
of gender differences.
AB - PURPOSE: The study aims to identify the occurrence and remission of statin
induced myopathy including patient perception and symptom characteristics with a
gender perspective. METHODS: The study was designed as a prospective, non
interventional investigation in 192 outpatients receiving statin treatment in
usual care with 12 months follow-up. Main outcome measure was myopathy related to
statin treatment and classified as probable using WHO criteria for adverse drug
reaction (ADR) assessment. RESULTS: Fourteen percent developed myopathy, risk
ratio for women 1.52 [95 % CI 1.37; 1.66] as compared to men. The majority graded
their pain as "severe." CK values were within normal range. Eighty percent of the
women compared to 43 % of the men reported that the muscular symptoms affected
their daily life activities to a moderate or severe extent. For those who stopped
treatment, mypopathy was the reason for 70 % of the women and 25 % of the men.
There was a difference in mean dose between men with and without myopathy, but
not in women. Among the patients with myopathy, 76 % reported other ADRs as
compared to 21 % of the patients without myopathy (p = 0.002). Twenty-nine
percent of the women and 18 % of the men reported other ADRs. CONCLUSION: Women
reported a higher frequency of myopathy and other ADRs as well as a larger impact
on daily life activities. In men, but not in women, the risk of myopathy was dose
dependent. Patients with myopathy were more susceptible to other statin-induced
ADRs which raises the question about common underlying mechanisms.
PMID- 27484242
TI - Prevention of selective outcome reporting: let us start from the beginning.
AB - BACKGROUND: Healthcare professionals and patients could be negatively influenced
in their judgments by articles and meta-analyses presenting selective outcome
reporting. Clinical trials should be transparent from inception to the
publication of results. To this end, trial prospective registration is an ethical
and scientific requirement that have shown to be effective in preventing
selective reporting of outcomes. However, even journals with a clear pre
registration policy publish trial results that were retrospectively registered.
SITUATION: Analyses of registration of randomized clinical trials recently
published in top specialty journals and of meta-analyses with suspicion of
including trials with outcome reporting bias have shown that retrospective
registration is in the range from 56 to 76 %. This translates into publication of
primary endpoints that differ from those included in the registry: some 30 % of
trials showed discrepancies between the primary endpoint in the trial registry
and the article. Furthermore, it has been shown that 8 % of all clinical trials
published by 6 high-impact ICMJE-member journals was retrospectively registered
after primary endpoint ascertainment could have had taken place, raising concerns
that endpoints may not have been pre-specified, or were changed. With regards to
meta-analyses, 34 % of Cochrane systematic reviews included one or more trials
with a high suspicion of selective reporting bias for the primary outcome.
PROPOSAL: Retrospective registration of trials may foster selective outcome
reporting unless journal editors implement specific quality control processes
aiming to prevent or minimize this type of bias. Prospective registration of
trials-and protocol public disclosure if proven effective in future studies
prevents outcome reporting bias, a must to ensure clinicians and patients have
access to reliable clinical trial results. Journal editors should enforce, rather
than encourage, appropriate measures to ensure publication of trials free of
outcome reporting bias.
PMID- 27484243
TI - Hepatoprotection and hepatotoxicity of Heshouwu, a Chinese medicinal herb:
Context of the paradoxical effect.
AB - Heshouwu (Polygonum multiflorum Thunb.) has been a common Chinese medicine and a
folk Taoist medicine for over a thousand years. There are two drug forms,
Shengshouwu (Polygoni Multiflori Radix) and Zhiheshouwu (Polygoni Multiflori
Radix Prapaerata) in the Chinese Pharmacopoeia. In this review, we retrieved
articles with such keywords as Heshouwu, liver protection and liver toxicity in
the databases of PubMed and the China National Knowledge Infrastructure (CNKI).
Hepatoprotection and hepatotoxicity of Shengshouwu and Zhiheshouwu in vitro and
in vivo, and their clinical settings and adverse drug reactions (ADR) were
summarized, analyzed and critically reviewed. In bench research, both drug forms
had effects against nonalcoholic fatty liver disease, oxidation, fibrosis,
cirrhosis, and liver cancer. Clinically, Heshouwu was used for treating fatty
liver disease (FLD), hyperlipidemia, cirrhosis and hepatitis B. In contrast, both
drug forms could lead to drug-induced liver injury and even death in vitro, in
vivo and in clinical settings. In addition, the active components of both drug
forms had hepatic benefits and toxicity in interaction with emodin, physcion, and
probably 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-d-glucoside (TSG). In
conclusion, Heshouwu exhibited both hepatoprotection and hepatotoxicity. It is
essential to evaluate the advantages and disadvantages when Heshouwu is in
clinical use.
PMID- 27484244
TI - In vivo evaluation of mutagenic and recombinagenic activities of Brazilian
propolis.
AB - Propolis is a resinous, complex mixture of compounds collected by the bee species
Apis mellifera. This study investigated the genotoxicity of green and brown
propolis collected in southeast Brazil using the somatic mutation and
recombination test (SMART) in Drosophila melanogaster. The effect of five
concentrations (0.5, 1.0, 2.0, 4.0, and 7.5 mg/mL) of both propolis types was
analyzed in standard (ST) and high-bioactivation (HB) crosses, which have normal
and high levels of cytochrome P450 enzymes, respectively. The results show that
the types of propolis evaluated have no mutagenic action, in either cross.
Moreover, chromatography findings revealed that the propolis types analyzed have
different chemical compositions. Brown propolis had lower levels of polyphenols
(~7.2 mg/mL), compared to the green type (34.9 mg/g). Taken together, the
findings of the present study and literature reports point to the safety in
consuming low amounts of propolis, considering the risk of genetic damage, and
confirm the absence of mutagenic and recombinagenic actions of the propolis types
investigated.
PMID- 27484245
TI - Space-related confabulations after right hemisphere damage.
AB - Confabulations usually refer to memory distortions, characterized by the
production of verbal statements or actions that are inconsistent with the
patient's history and present situation. However, behavioral patterns reminiscent
of memory confabulations can also occur in patients with right hemisphere damage,
in relation to their personal, peripersonal or extrapersonal space. Thus, such
patients may be unaware of their left hemiplegia and confabulate about it
(anosognosia), deny the ownership of their left limbs (somatoparaphrenia), insult
and hit them (misoplegia), or experience a "third", supernumerary left limb.
Right brain-damaged patients can also sometimes confabulate about the left,
neglected part of images presented in their peripersonal space, or believe to be
in another place (reduplicative paramnesia). We review here these instances of
confabulation occurring after right hemisphere damage, and propose that they
might reflect, at least partially, the attempts of the left hemisphere to make
sense of inappropriate input received from the damaged right hemisphere.
PMID- 27484246
TI - Direct evidence for role of anti-saliva antibodies against salivary gland
homogenate of P. argentipes in modulation of protective Th1-immune response
against Leishmania donovani.
AB - Currently the main concerns regarding control of visceral leishmaniasis (VL)
caused by L. donovani are immunosuppression, relating toxicity of anti
leishmanial drug and little development in appropriate vaccine and vector (P.
argentipes) control. Reports available from ex-vivo studies reflect significance
of vector salivary gland homogenate (SGH) in reverting immunosuppression of
infected VL subjects and as such the immunogenic nature of SGH can be a strategy
to modulate immune system and anti-leishmanial function to enable immune response
to control the disease. Several related studies also identified a better utility
of vector anti-saliva antibodies in achieving such effects by an adoptive
transfer approach instead of direct stimulation with SGH protein. However,
conclusive evidences on VL cases are far beyond satisfactory to suggest role of
SGH into modulation of host immune response in VL subjects in India. This study
was under taken to make comparison on change in cytokines (TH1 and TH2) response
pattern and anti-leishmanial macrophage (Mphi) function following stimulation of
their PBMCS with SGH protein derived from P. argentipes sand fly vector for VL or
anti SGH antibodies raised in rabbit. This study reports for the first time that
L. donovani sensitized healthy subject demonstrates an up-regulated Interferon
gamma (TH1) and down regulate Interleukin-10 (TH2) production following
stimulation of their PBMCs by P. argentipes anti-saliva antibodies accompanied
with an improvement in anti-leishmanial Mphi function for nitric oxide (NO)
production. Subsequent experiments suggest that P. argentipes based anti-SGH
antibodies when used to stimulate LD infected PBMCs in healthy subjects resulted
in better clearance of Leishmania amastigotes load compare to SGH protein.
Possibly the immunogenic components of anti-saliva an antibody maintains the
level of protective cytokine (INF-gamma) and seems to restrict the infection by
host protection by vector saliva.
PMID- 27484247
TI - In-silico optimisation of two-dimensional high performance liquid chromatography
for the determination of Australian methamphetamine seizure samples.
AB - In-silico optimisation of a two-dimensional high performance liquid
chromatography (2D-HPLC) separation protocol has been developed for the
interrogation of methamphetamine samples including model, real world seizure, and
laboratory synthesised samples. The protocol used Drylab((r)) software to rapidly
identify the optimum separation conditions from a library of chromatography
columns. The optimum separation space was provided by the Phenomonex Kinetex PFP
column (first dimension) and an Agilent Poroshell 120 EC-C18 column (second
dimension). To facilitate a rapid 2D-HPLC analysis the particle packed C18 column
was replaced with a Phenomenex Onyx Monolithic C18 withought sacrificing
separation performance. The Drylab((r)) optimised and experimental separations
matched very closely, highlighting the robust nature of HPLC simulations. The
chemical information gained from an intermediate methamphetamine sample was
significant and complimented that generated from a pure seizure sample. The
influence of the two-dimensional separation on the analytical figures of merit
was also investigated. The limits of detection for key analytes in the second
dimension determined for methamphetamine (4.59*10(-4)M), pseudoephedrine
(4.03*10(-4)M), caffeine (5.16*10(-4)M), aspirin (9.32*10(-4)M), paracetamol
(5.93*10(-4)M) and procaine (2.02*10(-3)M).
PMID- 27484248
TI - Can "contamination" occur in body bags?-The example of background fibres in body
bags used in Australia.
AB - Impurities that are transferred to a crime scene or a body can have a significant
negative impact on the investigation if the existence of the contamination is not
known, and the source of the contamination is not identified. Forensic
consumables, such as DNA swabs, have been known to have caused contaminations,
wrongfully linking crimes throughout Europe. In that context, this study focused
on body bags, widely used to transfer a corpse from the crime scene to the
morgue. Our preliminary survey showed that several countries and Australian
Jurisdictions are conducting the sampling of trace evidence at the morgue after
the transportation of the body. Potential impurities present in body bags could
thus interfere with pertinent traces. The aim of this work was to qualify and
quantify the background contamination of trace evidence in body bags used within
Australia. Fifteen body bags from four Australian Jurisdictions or laboratories
were searched for micro traces. Impurities such as fibres and unidentified
particles were detected in each examined body bag, with an estimated average of
3603 coloured fibres and 1429 unidentified particles. This number of fibres is
similar to the amount found on a vinyl cinema seat in other studies. Various
other contaminants such as pieces of fabric, hairs, parts of insects or feathers
were also observed. It is hypothesised that these impurities are introduced
during the manufacturing process. This high number of impurities can lead to
incorrect conclusions and misleading investigative leads. This paper presents an
overview of the problems these impurities can cause and proposes several
strategies to prevent future issues.
PMID- 27484249
TI - Evaluation of the Reliability of Cone-beam Computed Tomography Scanning and
Electronic Apex Locator Measurements in Working Length Determination of Teeth
with Large Periapical Lesions.
AB - INTRODUCTION: This study evaluates the endodontic working-length measurements in
teeth with large periapical lesions and persistent intracanal exudate by using
preexisting cone-beam computed tomography (CBCT). It compares the measurements
with clinical root canal lengths determined by using 2 electronic apex locators.
METHODS: All patients had undergone a CBCT scan independent of the present study
and needed root canal treatment of at least 1 tooth visible in the field of view.
Seventy-three teeth with single roots and canals were studied. An endodontist
measured each root canal length with 2 different electronic apex locators. The
measurements were repeated 3 times by using a digital caliper, and the mean was
recorded. This mean was compared with the root canal length as measured on CBCT
sections by an oral radiologist not involved in the endodontic treatment. The
CBCT measurements were taken twice for analysis of intrarater reliability. The
data were statistically analyzed. RESULTS: There were no significant measurement
differences between the methods used (P > .05). CONCLUSIONS: In teeth with large
periapical lesions and persistent intracanal exudate, measurement of the root
canal length by using CBCT was as reliable as measurements that used apex
locators.
PMID- 27484250
TI - Effects of a Bioactive Scaffold Containing a Sustained Transforming Growth Factor
beta1-releasing Nanoparticle System on the Migration and Differentiation of Stem
Cells from the Apical Papilla.
AB - INTRODUCTION: This 2-part study hypothesized that a bioactive scaffold containing
a sustained transforming growth factor (TGF)-beta1-releasing nanoparticle system
will promote migration and enhance differentiation of stem cells from the apical
papilla (SCAP). The study aimed to develop and characterize a novel modified
chitosan-based scaffold containing TGF-beta1-releasing chitosan nanoparticles
(TGF-beta1-CSnp) to enhance migration and differentiation of SCAP. METHODS: Part
I concerns the synthesis and characterization of a carboxymethyl chitosan-based
scaffold and TGF-beta1-CSnp. Part II examines the effect of sustained TGF-beta1
release from scaffold containing TGF-beta1-CSnp on odontogenic differentiation of
SCAP. RESULTS: The scaffold demonstrated properties conducive to cellular
activities. The incorporation of TGF-beta1 in CSnp allowed sustained release of
TGF-beta1, facilitating delivery of a critical concentration of TGF-beta1 at the
opportune time. TGF-beta1 bioactivity was maintained for up to 4 weeks. SCAP
showed greater viability, migration, and biomineralization in the presence of TGF
beta1-CSnp than in the presence of free TGF-beta1. SCAP cultured in TGF-beta1
CSnp + scaffold showed significantly higher dentin matrix protein-1 and dentin
sialophosphoprotein signals compared with free TGF-beta1 + scaffold or CSnp +
scaffold. CONCLUSIONS: These experiments highlighted the potential of a
carboxymethyl chitosan-based scaffold with growth factor releasing nanoparticles
to promote migration and differentiation of SCAP. The results of this study may
have direct application to improve current endodontic regenerative protocols.
PMID- 27484251
TI - Quality attributes and microbial survival on whole cantaloupes with antimicrobial
coatings containing chitosan, lauric arginate, cinnamon oil and
ethylenediaminetetraacetic acid.
AB - Cantaloupes are susceptible to microbiological contamination in pre- or
postharvest environments. Novel intervention strategies, such as antimicrobial
coatings, are needed to improve the microbiological safety of cantaloupes. The
objective of this study was to prepare whole cantaloupes coated with mixtures
containing chitosan, lauric arginate (LAE), cinnamon oil (CO), and
ethylenediaminetetraacetic acid (EDTA) and determine survival characteristics of
inoculated foodborne pathogens during storage as well as cantaloupe quality
attributes. Chitosan coating with 0.1% LAE, 0.1% EDTA, and 1% CO was the most
effective for inactivating foodborne pathogens inoculated on cantaloupes. This
coating caused a >3logCFU/cm(2) reduction of Escherichia coli O157:H7 and
Listeria monocytogenes immediately after coating and reduced Salmonella enterica
to below the detection limit during a 14-day storage. Total molds and yeasts also
were reduced to the detection limit by the coating. The redness and yellowness of
uncoated cantaloupes were significantly higher than coated ones from day 6. The
firmness of uncoated cantaloupes and those coated with chitosan only was
significantly lower than other treatments from day 10. No significant differences
were found in total soluble solids content or weight loss between coated and
uncoated cantaloupes. Results showed the potential benefits of applying the
coating mixtures to improve the quality and microbiological safety of
cantaloupes.
PMID- 27484252
TI - Social capital and refraining from medical care among elderly people in Japan.
AB - BACKGROUND: Refraining from required medical care can worsen health, particularly
for the elderly, and increase public medical expenditure, which destabilizes the
financial aspect of social security. Social capital, such as trust between
residents and the norms of reciprocity in the community, is a possible measure to
prevent refraining from medical care. METHODS: We studied survey data collected
in a small area in Japan that included a high response rate (91.6 %) to evaluate
refraining from medical care. Self-reported refraining from required medical care
from among 1016 elderly people, aged >=60 (male = 490; female = 526), was used as
a dependent variable. Social capital indicators were mean values of people's
attitude toward the generalized trust and norms of reciprocity in each community.
We estimated the association between community level social capital and
individuals' probability of refraining from medical care while controlling
individual factors such as age, education, and marital status. RESULTS: Logit
estimation results showed that only generalized trust is associated with low
probability of refraining from medical care among the elderly in small
communities. The marginal effect for 0.1 increase in community level trust is 4 %
decrease in the probability of refraining from medical care. In larger
communities, generalized trust is not associated with the probability of
refraining from medical care. CONCLUSIONS: This finding suggests that the
generalized trust is effective in smaller communities as far as related to access
to medical care. In small communities, policy to increase generalized trust to
support medical care for elderly is recommended.
PMID- 27484253
TI - Comprehending Sentences With the Body: Action Compatibility in British Sign
Language?
AB - Previous studies show that reading sentences about actions leads to specific
motor activity associated with actually performing those actions. We investigate
how sign language input may modulate motor activation, using British Sign
Language (BSL) sentences, some of which explicitly encode direction of motion,
versus written English, where motion is only implied. We find no evidence of
action simulation in BSL comprehension (Experiments 1-3), but we find effects of
action simulation in comprehension of written English sentences by deaf native
BSL signers (Experiment 4). These results provide constraints on the nature of
mental simulations involved in comprehending action sentences referring to
transfer events, suggesting that the richer contextual information provided by
BSL sentences versus written or spoken English may reduce the need for action
simulation in comprehension, at least when the event described does not map
completely onto the signer's own body.
PMID- 27484255
TI - Hemophagocytic lymphohistiocytosis with leukoencephalopathy in a patient with
dermatomyositis accompanied with peripheral T-cell lymphoma: a case report.
AB - BACKGROUND: Hemophagocytic lymphohistiocytosis associated with autoimmune
diseases is seen in patients with systemic juvenile idiopathic arthritis, adult
onset Still's disease, and systemic lupus erythematosus, whereas it is rarely
seen in patients with dermatomyositis. In addition, central nervous system
involvement with dermatomyositis is rare. To the best of our knowledge, this is
the first case of hemophagocytic lymphohistiocytosis complicated by
leukoencephalopathy in a patient with dermatomyositis accompanied with peripheral
T-cell lymphoma. CASE PRESENTATION: A 17-year-old Asian male adolescent with
dermatomyositis and hemophagocytic lymphohistiocytosis that were controlled with
corticosteroid therapy presented to our hospital with high fever and altered
consciousness. Brain magnetic resonance imaging revealed multiple cerebral
lesions. We diagnosed the central nervous system lesions as leukoencephalopathy
secondary to dermatomyositis and hemophagocytic lymphohistiocytosis. Because
corticosteroid and cyclophosphamide pulse therapy was ineffective, he was treated
with a modified hemophagocytic lymphohistiocytosis-2004 protocol, which resulted
in the disappearance of the lesions of his central nervous system. CONCLUSIONS:
Our findings suggest that the hemophagocytic lymphohistiocytosis-2004 protocol
including etoposide should be initiated immediately in patients with
hemophagocytic lymphohistiocytosis who respond poorly to treatment for the
underlying disease. Moreover, irrespective of the underlying disease, patients
with hemophagocytic lymphohistiocytosis with central nervous system lesions might
require bone marrow transplantation.
PMID- 27484256
TI - Anxiety associated with diagnostic uncertainty in early pregnancy.
AB - OBJECTIVES: To determine anxiety levels of women presenting to an early pregnancy
assessment unit (EPAU) with abdominal pain and/or vaginal bleeding and to assess
how these levels change over time and according to ultrasonographic diagnosis.
METHODS: We undertook a prospective cohort study in an EPAU in a large UK
teaching hospital. Women with abdominal pain and/or vaginal bleeding in early
pregnancy (< 12 weeks' gestation) presenting for the first time were eligible for
inclusion in the study. State anxiety levels were assessed using the standardized
short form of Spielberger's state-trait anxiety inventory (STAI) on three
occasions (before, immediately after and 48-72 hours after an ultrasound scan).
Scores were correlated with ultrasonographic diagnosis. The diagnosis was either
certain or uncertain. Certain diagnoses were either positive, i.e. a viable
intrauterine pregnancy (IUP), or negative, i.e. a non-viable IUP or ectopic
pregnancy. Uncertain diagnoses included pregnancy of unknown location and
pregnancy of uncertain viability. Statistical analysis involved mixed ANOVAs and
the post-hoc Tukey-Kramer test. RESULTS: A total of 160 women were included in
the study. Anxiety levels decreased over time for women with a certain diagnosis
(n = 128), even when negative (n = 64), and increased over time for women with an
uncertain diagnosis (n = 32). Before the ultrasound examination, anxiety levels
were high (STAI value, 21.96 +/- 1.11) and there was no significant difference
between the five groups. Immediately after the ultrasound examination, anxiety
levels were lower in the viable IUP group (n = 64; 7.75 +/- 1.13) than in any
other group. The difference between the five groups was significant (P < 0.005).
After 48-72 hours, women with a certain diagnosis had significantly lower anxiety
levels than had those with an uncertain diagnosis (10.77 +/- 4.30 vs 22.94 +/-
1.65; P < 0.005). CONCLUSIONS: The experience of abdominal pain and/or vaginal
bleeding in early pregnancy is highly anxiogenic. Following an ultrasound
examination, the certainty of the diagnosis affects anxiety levels more than does
the positive or negative connotations associated with the diagnosis per se.
Healthcare providers should be aware of this when communicating uncertain
diagnoses. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27484254
TI - A retrospective study of predictive factors for unexpectedly prolonged or
shortened progression-free survival and overall survival among patients with
metastatic renal cell carcinoma who received first-line targeted therapy.
AB - BACKGROUND: To identify predictors of prolonged or shortened progression-free
survival (PFS) and overall survival (OS) among patients with metastatic renal
cell carcinoma (mRCC) who received first-line targeted therapies. METHODS: This
retrospective study included 146 patients with mRCC who were treated during 2007
2015. These patients were divided into a group with the worst response (WG), an
expected group (EG), and a group with the best response (BG), based on their PFS
(<=3 monthsnths, 3-18 monthsnths, and >18 monthsnths, respectively) and OS (<1
year, 1-3 years, and >3 years, respectively). To identify significant predictive
factors, the BG and WG were compared to the EG using the Memorial Sloan Kettering
Cancer Center and Heng risk models. RESULTS: The overall PFS and OS were 9.3
months and 16.4 months, respectively. The median PFS for the WG (41.8 %), EG
(45.9 %), and BG (12.3 %) were 2.7 months, 9.3 months, and 56.6 months,
respectively, and the median OS for the WG (45.9 %), EG (35.6 %), and BG (18.5 %)
were 5.5 months, 21.6 months, and 63.1 months, respectively; these outcomes were
significantly different (p < 0.001). Nephrectomy (odds ratio [OR]: 7.15) was a
significant predictor of PFS in the BG, and the significant predictors of OS in
the BG were MSKCC intermediate risk (OR: 0.12), poor risk (OR: 0.04), and a
disease-free interval of <1 year (OR: 0.23) (all, p < 0.05). Anemia (OR: 3.25)
was a significant predictor of PFS in the WG, and the significant predictors of
OS were age (OR: 1.05), anemia (OR: 4.13), lymphocytopenia (OR: 4.76), disease
free interval of <1 year (OR: 4.8), and synchronous metastasis (OR: 3.52) (all, p
< 0.05). CONCLUSION: We identified several significant predictors of unexpectedly
good and poor response to first-line targeted therapy among patients with mRCC.
PMID- 27484257
TI - Characterising the extent of misreporting of high blood pressure, high
cholesterol, and diabetes using the Australian Health Survey.
AB - BACKGROUND: Measuring and monitoring the true prevalence of risk factors for
chronic conditions is essential for evidence-based policy and health service
planning. Understanding the prevalence of risk factors for cardiovascular disease
(CVD) in Australia relies heavily on self-report measures from surveys, such as
the triennial National Health Survey. However, international evidence suggests
that self-reported data may substantially underestimate actual risk factor
prevalence. This study sought to characterise the extent of misreporting in a
large, nationally-representative health survey that included objective measures
of clinical risk factors for CVD. METHODS: This study employed a cross-sectional
analysis of 7269 adults aged 18 years and over who provided fasting blood samples
as part of the 2011-12 Australian Health Survey. Self-reported prevalence of high
blood pressure, high cholesterol and diabetes was compared to measured
prevalence, and univariate and multivariate logistic regression analyses
identified socio-demographic characteristics associated with underreporting for
each risk factor. RESULTS: Approximately 16 % of the total sample underreported
high blood pressure (measured to be at high risk but didn't report a diagnosis),
33 % underreported high cholesterol, and 1.3 % underreported diabetes. Among
those measured to be at high risk, 68 % did not report a diagnosis for high blood
pressure, nor did 89 % of people with high cholesterol and 29 % of people with
high fasting plasma glucose. Younger age was associated with underreporting high
blood pressure and high cholesterol, while lower area-level disadvantage and
higher income were associated with underreporting diabetes. CONCLUSIONS:
Underreporting has important implications for CVD risk factor surveillance,
policy planning and decisions, and clinical best-practice guidelines. This
analysis highlights concerns about the reach of primary prevention efforts in
certain groups and implications for patients who may be unaware of their disease
risk status.
PMID- 27484258
TI - Context processing in adolescents with autism spectrum disorder: How complex
could it be?
AB - The ability of individuals with Autism Spectrum Disorder (ASD) to process context
has long been debated: According to the Weak Central Coherence theory, ASD is
characterized by poor global processing, and consequently-poor context
processing. In contrast, the Social Cognition theory argues individuals with ASD
will present difficulties only in social context processing. The complexity
theory of autism suggests context processing in ASD will depend on task
complexity. The current study examined this controversy through two priming
tasks, one presenting human stimuli (facial expressions) and the other presenting
non-human stimuli (animal faces). Both tasks presented visual targets, preceded
by congruent, incongruent, or neutral auditory primes. Local and global
processing were examined by presenting the visual targets in three spatial
frequency conditions: High frequency, low frequency, and broadband. Tasks were
administered to 16 adolescents with high functioning ASD and 16 matched typically
developing adolescents. Reaction time and accuracy were measured for each task in
each condition. Results indicated that individuals with ASD processed context for
both human and non-human stimuli, except in one condition, in which human stimuli
had to be processed globally (i.e., target presented in low frequency). The task
demands presented in this condition, and the performance deficit shown in the ASD
group as a result, could be understood in terms of cognitive overload. These
findings provide support for the complexity theory of autism and extend it. Our
results also demonstrate how associative priming could support intact context
processing of human and non-human stimuli in individuals with ASD. Autism Res
2017, 10: 520-530. (c) 2016 International Society for Autism Research, Wiley
Periodicals, Inc.
PMID- 27484259
TI - Enhancement of Tb(III) -Cu(II) Single-Molecule Magnet Performance through
Structural Modification.
AB - We report a series of 3d-4f complexes {Ln2 Cu3 (H3 L)2 Xn } (X=OAc(-) , Ln=Gd, Tb
or X=NO3 (-) , Ln=Gd, Tb, Dy, Ho, Er) using the 2,2'-(propane-1,3
diyldiimino)bis[2-(hydroxylmethyl)propane-1,3-diol] (H6 L) pro-ligand. All
complexes, except that in which Ln=Gd, show slow magnetic relaxation in zero
applied dc field. A remarkable improvement of the energy barrier to reorientation
of the magnetisation in the {Tb2 Cu3 (H3 L)2 Xn } complexes is seen by changing
the auxiliary ligands (X=OAc(-) for NO3 (-) ). This leads to the largest reported
relaxation barrier in zero applied dc field for a Tb/Cu-based single-molecule
magnet. Ab initio CASSCF calculations performed on mononuclear Tb(III) models are
employed to understand the increase in energy barrier and the calculations
suggest that the difference stems from a change in the Tb(III) coordination
environment (C4v versus Cs ).
PMID- 27484260
TI - Thoracoscopic lobectomy for lung cancer in a patient with a partial anomalous
pulmonary venous connection: a case report.
AB - BACKGROUND: A partial anomalous pulmonary venous connection is a rare congenital
defect in which blood from the pulmonary vein is returned to the right atrium.
Asymptomatic patients with a partial anomalous pulmonary venous connection with a
small left-to-right shunt do not require surgical treatment. If such patients
require a major lung resection, the surgical procedure could precipitate fetal
right heart failure if the anomalous venous connection remains uncorrected. CASE
PRESENTATION: A 59-year-old man was found to have an abnormal shadow on chest
roentgenogram. Chest computed tomography imaging showed a mass in the right upper
lobe. At the same time, we incidentally found an anomalous vessel. We diagnosed
the abnormality as a partial anomalous pulmonary venous connection. Because the
mass may have been lung cancer, a right upper lobectomy was performed using video
assisted thoracoscopic surgery. The right upper lobe vein drained into the
superior vena cava. The anomaly was not corrected and the surgery was successful.
His postoperative course was uneventful without cardiac failure. CONCLUSIONS:
Before performing a major lung resection, surgeons should be aware of this rare
anomaly and carefully interpret clinical images of all pulmonary veins.
PMID- 27484263
TI - The expanding role of methotrexate for treating skin disease.
PMID- 27484261
TI - Wheat bran components modulate intestinal bacteria and gene expression of barrier
function relevant proteins in a piglet model.
AB - The objective of this study was to determine the impact of wheat bran and its
main polysaccharides on intestinal bacteria and gene expression of intestinal
barrier function relevant proteins. Thirty freshly weaned male piglets were
assigned randomly to five dietary treatment groups with six piglets per group.
Accordingly, five synthetic diets including a basal control diet without fiber
components (CON), wheat bran diet (10% wheat bran, WB), arabinoxylan diet (AX),
cellulose diet (CEL) and combined diet of arabinoxylan and cellulose (CB) were
studied. The piglets were fed ad libitum for 30 d. Lower Escherichia coli (E.
coli) populations in WB group and higher probiotic (Lactobacillus and
Bifidobacterium) populations in groups fed diets containing arabinoxylan (WB, AX
and CB) were observed and compared with CON group. Compared with CON group, the
gene expressions of cystic fibrosis transmembrane conductance regulator (CFTR),
calcium-activated chloride channel regulator 1 (CLCA1) and voltage-gated chloride
channel 2 (CIC2) were suppressed in the WB group. And wheat bran down-regulated
gene expression of pro-inflammation (TNF-alpha, IL-1beta, IL-6) and TLRs/MyD88/NF
kappaB pathway compared with CON group. In conclusion, wheat bran and its main
polysaccharides could change intestinal microflora and down-regulate the gene
expression of intestinal barrier function relevant proteins in the distal small
intestinal mucosa.
PMID- 27484264
TI - Bookish inclinations.
PMID- 27484265
TI - Hirsutism management needs to be more patient oriented.
PMID- 27484266
TI - Helicobacter cinaedi - an emerging form of cellulitis.
PMID- 27484267
TI - Cutaneous T-cell lymphomas: an urgent need for more improved therapies.
PMID- 27484268
TI - Collaboration between dermatologists and dentists in autoimmune bullous diseases
and immunoglobulin A antibodies in pemphigus.
PMID- 27484269
TI - Is there a pathogenic role for IgE in psoriasis?
PMID- 27484270
TI - CARD14 mutations may predict response to antitumour necrosis factor-alpha therapy
in psoriasis: a potential further step towards personalized medicine.
PMID- 27484271
TI - Quantifying disease extent in pemphigus.
PMID- 27484272
TI - Discordance between physician assessment of psoriasis and patient self
assessment: the importance of itch.
PMID- 27484273
TI - Deciphering the lipidomic profile of irritant contact dermatitis.
PMID- 27484274
TI - Not the usual suspect: a case of basal cell naevus syndrome caused by a SMO
mutation alone.
PMID- 27484275
TI - British Association of Dermatologists' guidelines for the safe and effective
prescribing of methotrexate for skin disease 2016.
PMID- 27484276
TI - An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting
simultaneous kidney and pancreas transplantation for type 1 diabetes.
AB - Malignant melanoma is a high-risk skin cancer that, in potential transplant
recipients, is considered a substantial contraindication to solid organ
transplantation due to significant risk of recurrence with immunosuppression.
Current guidelines stipulate waiting between 3 and 10 years after melanoma
diagnosis. However, in young patients with end-stage organ failure and malignant
melanoma, complex ethical and moral issues arise. Assessment of the true risk
associated with transplantation in these patients is difficult due to lack of
prospective data, but an autonomous patient can make a decision that clinicians
may perceive to be high risk. The national and worldwide shortage of available
organs also has to be incorporated into the decision to maximize the net benefit
and minimize the risk of graft failure and mortality. The incidence of malignant
melanoma worldwide is increasing faster than that of any other cancer and
continues to pose ethically challenging decisions for transplant specialists
evaluating recipients for solid organ transplantation.
PMID- 27484278
TI - Corrigenda.
PMID- 27484277
TI - Cover Image: Acquired generalized lipodystrophy in a patient with systemic lupus
erythematosus.
PMID- 27484279
TI - Corrigenda.
PMID- 27484281
TI - Corrigenda.
PMID- 27484280
TI - Corrigenda.
PMID- 27484283
TI - Image Gallery: Dermoscopy of phthiriasis pubis: a handy and useful tool.
PMID- 27484286
TI - Duration of action of two insulin glargine products, LY2963016 insulin glargine
and Lantus insulin glargine, in subjects with type 1 diabetes mellitus.
AB - AIMS: LY2963016 (LY IGlar) and Lantus (IGlar) are insulin glargine products
manufactured by distinct processes, but with identical amino acid sequences. This
study compared the duration of action of LY IGlar and IGlar in subjects with type
1 diabetes mellitus (T1DM). MATERIALS AND METHODS: This was a randomized, double
blind, single-dose, two-period, crossover study. Twenty subjects underwent 42
hour euglycaemic clamps after a single subcutaneous 0.3-U/kg dose of LY IGlar or
IGlar. In this study, the duration of action was defined as the time required for
blood glucose levels to rise consistently above a predefined cut-off of 8.3
mmol/L (150 mg/dL) from a state of euglycaemia. Blood samples were collected to
measure blood glucose for pharmacodynamic (PD) evaluations. RESULTS: End of
action was reached within 42 hours in 26 of 40 clamps (13 LY IGlar and 13 IGlar).
The median duration of action for all subjects was 37.1 and 40.0 hours, and the
mean duration of action (calculated using only patients who reached end of
action) was 23.8 and 25.5 hours for LY IGlar and IGlar, respectively. The
duration of action was demonstrated to be similar between the treatments using
time-to-event analysis (log-rank test of equality p = .859). Following
administration of LY IGlar and IGlar, the PD parameters of maximum glucose
infusion rate (R max ) and total glucose infusion during the clamp (G tot ) were
comparable. CONCLUSION: LY IGlar and IGlar had similar duration of action and
comparable PD parameters in subjects with T1DM.
PMID- 27484287
TI - Extraction and isolation of lithospermic acid B from Salvia miltiorrhiza Bunge
using aqueous two-phase extraction followed by high-performance liquid
chromatography.
AB - A rapid and effective method integrating separation and purification of
lithospermic acid B from Salvia miltiorrhiza Bunge was developed by combining an
aqueous two-phase system extraction with preparative chromatography. An aqueous
two-phase system of n-butyl alcohol/KH2 PO4 was chosen from seven systems. The
influence of parameters including concentration of KH2 PO4 , n-butyl alcohol
concentration, pH, and the ratio of an aqueous two-phase system to crude extract
were investigated using a single factor design. Response surface methodology was
subsequently used to find the optimal compositions of an aqueous two-phase
system. Keeping a solvent-to-solid ratio of 10, the final optimized composition
of an aqueous two-phase system was 39.1% w/w n-butyl alcohol and 22.6% w/w KH2
PO4 . Under these conditions a recovery yield of 99.8% and a high partition
coefficient of 310.4 were obtained. In a pilot-scale experiment using optimized
conditions, 18.79 g of lithospermic acid B with a purity of 70.5% and in a yield
of 99.8% was separated from 0.5 kg of crude extract. Subsequently, 9.94 g
lithospermic acid B with a purity of 99.3% and recovery yield of 70.3% was
obtained with a preparative chromatographic process, and the two-step total
recovery was 70.1%.
PMID- 27484288
TI - The future of academic innovation in the field of medical devices: is innovation
still possible in orthopedics?
AB - Academic research is essential to bring disruptive innovation on medical devices
market because the risk-taking is too high for companies and their investors.
Performing clinical trials is essential to technical files but no one wants to
accept responsibility for implanted off-label devices. The paper explains the
academic process for innovation. We see that academic research depends, at the
end, on the motivation of companies to develop a product. The key to innovation
stands in the early collaboration between the surgeons, the research teams and
the companies in a project. Innovation is a good idea supported by the expertise
of the right people at the right moment. In orthopaedics, we need, more than
ever, to stay focused on the patient benefits.
PMID- 27484289
TI - MicroRNA-491 regulates the proliferation and apoptosis of CD8(+) T cells.
AB - T lymphocyte-mediated immune responses are critical for antitumour immunity;
however, T cell function is impaired in the tumour environment. MicroRNAs are
involved in regulation of the immune system. While little is known about the
function of intrinsic microRNAs in CD8(+) T cells in the tumour microenvironment.
Here, we found that miR-491 was upregulated in CD8(+) T cells from mice with
colorectal cancer. Retroviral overexpression of miR-491 in CD8(+) and CD4(+) T
cells inhibited cell proliferation and promoted cell apoptosis and decreased the
production of interferon-gamma in CD8(+) T cells. We found that miR-491 directly
targeted cyclin-dependent kinase 4, the transcription factor T cell factor 1 and
the anti-apoptotic protein B-cell lymphoma 2-like 1 in CD8(+) T cells.
Furthermore, tumour-derived TGF-beta induced miR-491 expression in CD8(+) T
cells. Taken together, our results suggest that miR-491 can act as a negative
regulator of T lymphocytes, especially CD8(+) T cells, in the tumour environment;
thus, this study provides a novel insight on dysfunctional CD8(+) T cells during
tumourigenesis and cancer progression. In conclusion, miR-491 may be a new target
for antitumour immunotherapy.
PMID- 27484290
TI - The HOVON68 CLL trial revisited: performance status and comorbidity affect
survival in elderly patients with chronic lymphocytic leukemia.
AB - In the HOVON68 CLL trial, patients 65 to 75 years of age had no survival benefit
from the addition of low-dose alemtuzumab to fludarabine and cyclophosphamide
(FC) in contrast to younger patients. The reasons are explored in this 5-year
trial update using both survival analysis and competing risk analysis on non-CLL
related mortality. Elderly FCA patients died more frequently from causes not
related to CLL, and more often related to comorbidity (mostly cardiovascular)
than to infection. In a Cox multivariate analysis, del(17p), performance status
>0, and comorbidity were associated with a higher non-CLL-related mortality in
the elderly independent of the treatment modality. Thus, while the 'fit' elderly
with no comorbidity or performance status of 0 might potentially benefit from
chemo-immunotherapy with FC, caution is warranted, when considering alemtuzumab
treatment in elderly patients with cardiovascular comorbidity.
PMID- 27484291
TI - Whole-animal genome-wide RNAi screen identifies networks regulating male germline
stem cells in Drosophila.
AB - Stem cells are regulated both intrinsically and externally, including by signals
from the local environment and distant organs. To identify genes and pathways
that regulate stem-cell fates in the whole organism, we perform a genome-wide
transgenic RNAi screen through ubiquitous gene knockdowns, focusing on regulators
of adult Drosophila testis germline stem cells (GSCs). Here we identify 530 genes
that regulate GSC maintenance and differentiation. Of these, we further knock
down 113 selected genes using cell-type-specific Gal4s and find that more than
half were external regulators, that is, from the local microenvironment or more
distal sources. Some genes, for example, versatile (vers), encoding a
heterochromatin protein, regulates GSC fates differentially in different cell
types and through multiple pathways. We also find that mitosis/cytokinesis
proteins are especially important for male GSC maintenance. Our findings provide
valuable insights and resources for studying stem cell regulation at the
organismal level.
PMID- 27484293
TI - ESICM LIVES 2014.
PMID- 27484292
TI - Effect of high pressure treatment on the aging characteristics of Chinese liquor
as evaluated by electronic nose and chemical analysis.
AB - Several high pressure (HP) treatments (100-400 MPa; 15 and 30 min) were applied
to Chinese "Junchang" liquor, and aging characteristics of the liquor were
evaluated. Results from the principal component analysis and the discriminant
factor analysis of E-Nose demonstrated that HP treatment at 300 and 400 MPa
resulted in significant (p < 0.05) changes in aroma components of the liquor. An
increase in total ester content and a decrease in total acid content were
observed for all treated samples (p < 0.05), which was verified by gas
chromatography analysis. In addition, a slight decrease in alcohol content was
found for HP treatment at 400 MPa for 30 min. These changes and trends were in
accordance with the natural aging process of Chinese liquor. However, HP
treatment caused a slight increase in solid content, which might be somewhat
undesirable. Sensory evaluation results confirmed that favorable changes in color
and flavor of Chinese liquor were induced by HP treatment; however, overall gaps
still existed between the quality of treated and six-year aged samples. HP
treatment demonstrated a potential to accelerate the natural aging process for
Chinese liquor, but long term studies may be needed further to realize the full
potential.
PMID- 27484294
TI - Assessment of antisperm antibodies in a sample of Egyptian patients with
hepatitis C virus infection.
AB - Association of hepatitis C virus (HCV) with autoimmune phenomena and impaired
semen parameters has been previously reported. The aim of this study was to
investigate the influence of HCV infection on the development of antisperm
antibodies (ASAs) in HCV-positive males. The study was conducted on 30 HCV
infected individuals and 30 healthy control subjects. In both patients and
control groups, liver enzymes and reproductive hormones were measured; computer
assisted semen analysis (CASA) was performed; HCV-RNA in serum was measured and
IgG and IgA ASAs in semen were determined. Free testosterone, sperm
concentration, progressive and total motility were significantly lower in HCV
patients than in the control group, whereas ASAs of the IgG and IgA classes were
significantly higher in HCV patients. However, correlations between viral load
and the examined semen parameters and ASAs were nonsignificant. In conclusion,
HCV may be responsible for the increased ASAs detected in HCV patients in the
present study, possibly providing another plausible explanation for the decreased
sperm motility reported in HCV patients. These findings could be of value in
fertility management of HCV patients.
PMID- 27484295
TI - Laser cooling in solids: advances and prospects.
AB - This review discusses the progress and ongoing efforts in optical refrigeration.
Optical refrigeration is a process in which phonons are removed from a solid by
anti-Stokes fluorescence. The review first summarizes the history of optical
refrigeration, noting the success in cooling rare-earth-doped solids to cryogenic
temperatures. It then examines in detail a four-level model of rare-earth-based
optical refrigeration. This model elucidates the essential roles that the various
material parameters, such as the spacing of the energy levels and the radiative
quantum efficiency, play in the process of optical refrigeration. The review then
describes the experimental techniques for cryogenic optical refrigeration of rare
earth-doped solids employing non-resonant and resonant optical cavities. It then
examines the work on laser cooling of semiconductors, emphasizing the differences
between optical refrigeration of semiconductors and rare-earth-doped solids and
the new challenges and advantages of semiconductors. It then describes the
significant experimental results including the observed optical refrigeration of
CdS nanostructures. The review concludes by discussing the engineering challenges
to the development of practical optical refrigerators, and the potential
advantages and uses of these refrigerators.
PMID- 27484296
TI - Prevalence of prediabetes and its association with obesity among college students
in Kuwait: A cross-sectional study.
AB - This cross-sectional study sought to estimate the prevalence of prediabetes and
assess its association with obesity among young adults in Kuwait; a country with
a high prevalence of obesity and diabetes. The estimated prevalence of
prediabetes was 6.3% (95% CI: 4.8-8.1) and obesity was associated with elevated
prediabetes prevalence.
PMID- 27484298
TI - Characteristics and Outcomes of Blood Product Transfusion During Critical Care
Transport.
AB - BACKGROUND: Civilian out-of-hospital transfusions have not been adequately
studied. This study seeks to characterize patients receiving out-of-hospital
blood product transfusion during critical care transport. STUDY DESIGN AND
METHODS: We studied patients transported by a regional critical care air-medical
service who received blood products during transport. This service carries two
units of uncrossmatched packed Red Blood Cells (pRBCs) on every transport in
addition to blood obtained from referring facilities. The pRBC are administered
according to a protocol for the treatment of hemorrhagic shock or based on
medical command physician order. Transfusion amount was categorized into three
groups based on the volume transfused (<350 mL, 350-700 mL, >700 mL). The
association between prehospital transfusion and in-hospital outcomes (mortality,
subsequent blood transfusion and emergent surgery) was estimated using logistic
regression models, controlling for age, first systolic blood pressure, first
heart rate, Glasgow Coma Score, time of transfer, and length of hospital
admission. RESULTS: Among the 1,440 critical care transports with transfusions
examined, 81% were for medical patients, being gastrointestinal hemorrhage the
most common indication (26%, CI 24-28%). pRBC transfusions were associated with
emergent surgery (OR = 1.81, 95% CI = 1.31-2.52) and in-hospital transfusions (OR
= 2.00, 95% CI = 1.46-2.76). Those with transfusions >700 mL were associated with
emergent surgery (OR = 1.79, 95% CI = 1.10-2.92) and mortality (OR = 2.11; 95% CI
= 1.21-3.69). CONCLUSIONS: In this sample, the majority of patients receiving
blood products during air-medical transport were transfused for medic conditions;
gastrointestinal hemorrhage was the most common chief complaint. The pRBC
transfusions were associated with emergent surgery and in-hospital transfusion.
Transfusions of >700 mL were associated with mortality.
PMID- 27484299
TI - One-year effects of two intensive inpatient treatments for severely obese
children and adolescents.
AB - BACKGROUND: Intensive inpatient lifestyle treatment may be a suitable alternative
for severely obese children and adolescents who do not benefit from ambulatory
obesity treatment. The aim was to evaluate the effectiveness of two intensive one
year lifestyle treatments with varying inpatient periods for severely obese
children and adolescents with regard to SDS-BMI and cardiometabolic risk factors.
METHODS: The study was designed as a randomized controlled trial with two active
treatment groups. Eighty participants (8-19 years) with severe obesity received
treatment at a specialized childhood obesity center in the Netherlands. Severe
obesity was defined as a SDS-BMI >= 3.0 or a SDS-BMI >= 2.3 in combination with
obesity-related comorbidity. Participants received an intensive one-year
lifestyle treatment with an inpatient period of either two months and biweekly
return visits during the next four months (short-stay group) or six months (long
stay group), both followed by six monthly return visits. Outcomes were assessed
at baseline, six and 12 months and included SDS-BMI as primary outcome and
cardiometabolic risk factors such as SDS-waist circumference, systolic- and
diastolic blood pressure, and blood measurements as secondary outcomes. To
evaluate differences in the course of the primary- and secondary outcomes over
time between the two treatment groups, Generalized Estimating Equations (GEE)
were performed. RESULTS: No differences in the course of SDS-BMI or secondary
outcomes over time were found between the two treatment groups after one year of
treatment. SDS-BMI decreased statistically significantly after one year of
treatment compared with baseline in both groups (0.33 (0.48) in the short-stay
and 0.52 (0.49) in the long-stay group). Similar results were found for SDS-waist
circumference, diastolic blood pressure and HDL-cholesterol. CONCLUSIONS: Since
there were no significant differences in effects between the short- and long-stay
treatment and considering the burden of the long-stay treatment for children and
families, we recommend implementation of the short-stay treatment. TRIAL
REGISTRATION: Netherlands Trial Register NTR1678 , registered 20-Feb-2009.
PMID- 27484300
TI - Engineering Saccharomyces cerevisiae for improvement in ethanol tolerance by
accumulation of trehalose.
AB - A genetic recombinant Saccharomyces cerevisiae starter with high ethanol
tolerance capacities was constructed. In this study, the gene of trehalose-6
phosphate synthase (encoded by tps1), which catalyzes the first step in trehalose
synthesis, was cloned and overexpressed in S. cerevisiae. Moreover, the gene of
neutral trehalase (encoded by nth1, trehalose degrading enzyme) was deleted by
using a disruption cassette, which contained long flanking homology regions of
nth1 gene (the upstream 0.26 kb and downstream 0.4 kb). The engineered strain
increased its tolerance against ethanol and glucose stress. The growth of the
wild strain was inhibited when the medium contained 6 % or more ethanol, whereas
growth of the engineered strain was affected when the medium contained 10 % or
more ethanol. There was no significant difference in the ethanol yield between
the wild strain and the engineered strain when the fermentation broth contained
10 % glucose (p > 0.05). The engineered strain showed greater ethanol yield than
the wild type strain when the medium contained more than 15 % glucose (p < 0.05).
Higher intracellular trehalose accumulation by overexpression of tps1 and
deletion of nth1 might provide the ability for yeast to protect against
environmental stress.
PMID- 27484301
TI - Estimating the probability of coexistence in cross-feeding communities.
AB - The dynamics of many microbial ecosystems are driven by cross-feeding
interactions, in which metabolites excreted by some species are metabolised
further by others. The population dynamics of such ecosystems are governed by
frequency-dependent selection, which allows for stable coexistence of two or more
species. We have analysed a model of cross-feeding based on the replicator
equation, with the aim of establishing criteria for coexistence in ecosystems
containing three species, given the information of the three species' ability to
coexist in their three separate pairs, i.e. the long term dynamics in the three
two-species component systems. The triple-system is studied statistically and the
probability of coexistence in the species triplet is computed for two models of
species interactions. The interaction parameters are modelled either as
stochastically independent or organised in a hierarchy where any derived
metabolite carries less energy than previous nutrients in the metabolic chain. We
differentiate between different modes of coexistence with respect to the pair
wise dynamics of the species, and find that the probability of coexistence is
close to 12 for triplet systems with three pair-wise coexistent pairs and for the
so-called intransitive systems. Systems with two and one pair-wise coexistent
pairs are more likely to exist for random interaction parameters, but are on the
other hand much less likely to exhibit triplet coexistence. Hence we conclude
that certain species triplets are, from a statistical point of view, rare, but if
allowed to interact are likely to coexist. This knowledge might be helpful when
constructing synthetic microbial communities for industrial purposes.
PMID- 27484302
TI - Examining the Relationship Between Traumatic Brain Injury and Substance Use
Outcomes in the Canadian Population.
AB - BACKGROUND: The literature has opposing views regarding the magnitude of the
association between substance use and TBI. Most studies have examined clinical
samples which are not representative of the entire head injured population.
Clinical samples provide very limited insight into TBI patients whom do not seek
care. OBJECTIVES: This paper examines the associations between TBI and substance
use/misuse. Its primary aim is to test whether or not individuals with a past
year TBI have higher rates of substance use/misuse than Canadians without a TBI
or back and/or spine injury controls drawing on self-report population level
data. METHODS: Using the 2009-2010 Canadian Community Health Survey, a nationally
representative cross-sectional survey of Canadians 12 years and older, this paper
assessed substance use (i.e., illicit drug use; drinking and binge drinking;
current smoking) among those with a TBI, as compared to two control groups: (1)
individuals with a back or spinal injury (BSI); and (2) healthy noninjured
controls. Multivariate regressions (logistic and multinomial), both unadjusted
and adjusting for a range of injury and sociodemographic covariates, were used in
hypothesis testing. RESULTS: Those with a past-year TBI demonstrated
significantly elevated rates of illicit drug use relative to non-injured
Canadians. Relative to the BSI group those with a TBI were less likely to drink
alcohol, did not differ in binge drinking, cigarette smoking and illicit drug
use. CONCLUSION: Health care professionals working with the TBI population should
integrate screening, brief intervention, and referral programming as a means to
reduce future harm related to substance misuse.
PMID- 27484303
TI - Coding in 2D: Using Intentional Dispersity to Enhance the Information Capacity of
Sequence-Coded Polymer Barcodes.
AB - A 2D approach was studied for the design of polymer-based molecular barcodes.
Uniform oligo(alkoxyamine amide)s, containing a monomer-coded binary message,
were synthesized by orthogonal solid-phase chemistry. Sets of oligomers with
different chain-lengths were prepared. The physical mixture of these uniform
oligomers leads to an intentional dispersity (1st dimension fingerprint), which
is measured by electrospray mass spectrometry. Furthermore, the monomer sequence
of each component of the mass distribution can be analyzed by tandem mass
spectrometry (2nd dimension sequencing). By summing the sequence information of
all components, a binary message can be read. A 4-bytes extended ASCII-coded
message was written on a set of six uniform oligomers. Alternatively, a 3-bytes
sequence was written on a set of five oligomers. In both cases, the coded binary
information was recovered.
PMID- 27484304
TI - Herpes simplex virus type 1 and type 2 in the Netherlands: seroprevalence, risk
factors and changes during a 12-year period.
AB - BACKGROUND: Genital herpes results in considerable morbidity, including risk of
neonatal herpes, and is increasingly being caused by Herpes Simplex Virus (HSV)
type 1. Possibly children are less often HSV-1 infected, leaving them susceptible
until sexual debut. We assessed changes in the Dutch HSV-1 and HSV-2
seroprevalence over time and determinants associated with HSV seropositivity.
METHODS: We used data from two population-based seroepidemiological studies
conducted in 1995-6 and 2006-7 with a similar study design. Serum samples of 6
months to 44-year-old participants were tested for type-specific HSV antibodies
using HerpesSelect(r) with a cut-off level of >1.10 for seropositivity. Age and
sex-specific HSV-1 and HSV-2 seroprevalence was weighted for the Dutch
population. Logistic regression was performed to investigate determinants
associated with HSV seropositivity. RESULTS: Overall, weighted HSV-1
seroprevalence was significantly lower in 2006-7 [42.7 % 95 % confidence interval
(CI) 39.9-45.4] than in 1995-6 (47.7 % 95 % CI 44.8-50.7), especially among 10-
to 14-year-olds. Overall, weighted HSV-2 seroprevalence remained stable: 6.8 % in
1995-6 and 6.0 % in 2006-7. Adults who ever had sexual intercourse were more
often seropositive for HSV-1 [adjusted Odds Ratio (aOR) 1.69 95 % CI 1.33-2.16]
and HSV-2 (aOR 2.35 95 % CI 1.23-4.52). Age at sexual debut was the only sexual
risk determinant associated with HSV-1 seropositivity. CONCLUSIONS: Because of
the lower HSV-1 seroprevalence in 2006-7 compared to 1995-6, more adults are
susceptible to genital HSV-1, including women of reproductive age. Given the
higher risk of neonatal herpes when HSV is acquired during pregnancy, prevention
and control measures during pregnancy also targeting HSV-1, are important.
PMID- 27484305
TI - Effects of arbuscular mycorrhizal fungi on CH4 emissions from rice paddies.
AB - Arbuscular mycorrhizal fungi (AMF) play a key role in soil carbon storage and
release; however, they have never been considered as a factor affecting methane
(CH4) emissions from rice paddies. To reveal the role of AMF, the diurnal
variations of CH4 emissions from the noninoculated and inoculated rice field
plots were compared at midseason drainage, reflooding stage, and end-of-season
drainage. The results showed that the diurnal variation patterns in the two
treatments both closely tracked soil water content at midseason drainage and end
of-season drainage, while correlated very well with the stomatal conductance of
rice at reflooding stage. There were no significant differences between
treatments in soil water content and stomatal conductance. However, the diurnal
CH4 emission fluxes at the three stages ranged from 4.8 to 39.3, 0.9 to 12.4, and
0.2 to 2.3 mg m-2 h-1 in the noninoculated plots, and those in the inoculated
plots ranged from 2.1 to 18.7, 0.9 to 5.0, and 0.3 to 1.2 mg m-2 h-1. The
significant differences resulted from carbon-to-nitrogen ratios (C:N) of the
noninoculated and inoculated soil, which had a negative linear correlation with
maximum diurnal CH4 fluxes. Compared with the noninoculated treatment,
inoculating with AMF significantly increased soil C:N by improving the dry matter
of rice, which intensified N limit for CH4 production.
PMID- 27484306
TI - Expanding the phenotypic spectrum of Succinyl-CoA ligase deficiency through
functional validation of a new SUCLG1 variant.
AB - Deficiency of the TCA cycle enzyme Succinyl-CoA Synthetase/Ligase (SCS), due to
pathogenic variants in subunits encoded by SUCLG1 and SUCLA2, causes
mitochondrial encephalomyopathy, methylmalonic acidemia, and mitochondrial DNA
(mtDNA) depletion. In this study, we report an 11year old patient who presented
with truncal ataxia, chorea, hypotonia, bilateral sensorineural hearing loss and
preserved cognition. Whole exome sequencing identified a heterozygous known
pathogenic variant and a heterozygous novel missense variant of uncertain
clinical significance (VUS) in SUCLG1. To validate the suspected pathogenicity of
the novel VUS, molecular and biochemical analyses were performed using primary
skin fibroblasts from the patient. The patient's cells lack the SUCLG1 protein,
with significantly reduced levels of SUCLA2 and SUCLG2 protein. This leads to
essentially undetectable SCS enzyme activity, mtDNA depletion, and cellular
respiration defects. These abnormal phenotypes are rescued upon ectopic
expression of wild-type SUCLG1 in the patient's fibroblasts, thus functionally
confirming the pathogenic nature of the SUCLG1 VUS identified in this patient and
expanding the phenotypic spectrum for SUCLG1 deficiency.
PMID- 27484307
TI - Stable isotope composition of cocoa beans of different geographical origin.
AB - The isotopic profile (delta(13) C, delta(15) N, delta(18) O, delta(2) H,
delta(34) S) was used to characterise a wide selection of cocoa beans from
different renowned production areas (Africa, Asia, Central and South America).
The factors most influencing the isotopic signatures of cocoa beans were climate
and altitude for delta(13) C and the isotopic composition of precipitation water
for delta(18) O and delta(2) H, whereas delta(15) N and delta(34) S were
primarily affected by geology and fertilisation practises. Multi-isotopic
analysis was shown to be sufficiently effective in determining the geographical
origin of cocoa beans, and combining it with Canonical Discriminant Analysis led
to more than 80% of samples being correctly reclassified. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27484308
TI - Anatomical imbalance between cortical networks in autism.
AB - Influential psychological models of autism spectrum disorder (ASD) have proposed
that this prevalent developmental disorder results from impairment of global
(integrative) information processing and overload of local (sensory) information.
However, little neuroanatomical evidence consistent with this account has been
reported. Here, we examined relative grey matter volumes (rGMVs) between three
cortical networks, how they changed with age, and their relationship with core
symptomatology. Using public neuroimaging data of high-functioning ASD males and
age-/sex-/IQ-matched controls, we first identified age-associated atypical
increases in rGMVs of the regions of two sensory systems (auditory and visual
networks), and an age-related aberrant decrease in rGMV of a task-control system
(fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the
auditory network in ASD adults was associated with the severity of autistic socio
communicational core symptom, that of the visual network was instead correlated
with the severity of restricted and repetitive behaviours in ASD. Notably, the
atypically decreased rGMV of FPN predicted both of the two core symptoms. These
findings suggest that disproportionate undergrowth of a task-control system (FPN)
may be a common anatomical basis for the two ASD core symptoms, and relative
overgrowth of the two different sensory systems selectively compounds the
distinct symptoms.
PMID- 27484309
TI - Indications to Epigenetic Dysfunction in the Pathogenesis of Common Variable
Immunodeficiency.
AB - Primary immunodeficiencies (PIDs) are a group of rare genetic diseases resulting
in the impairment of one or more functions of the human immune system. Common
variable immunodeficiency (CVID) is one of the most prevalent PIDs, yet despite
extensive genetic analysis, most patients do not have a monogenetic diagnosis.
This has led to the theory that CVID must be a polygenetic condition. An
alternative theory to a monogenetic or polygenetic underlying cause of CVID is
that it is epigenetic phenomena that are causal in the majority of CVID patients.
I will briefly discuss epigenetic regulation in B-cell biology and development,
current examples of epigenetic diseases causing CVID-like primary antibody
deficiencies, and how these observations may guide future investigation into the
role of epigenetics in CVID.
PMID- 27484310
TI - Insulin degludec + liraglutide: a complementary combination.
AB - INTRODUCTION: The treatment of patients with type 2 diabetes mellitus remains
challenging, as it goes beyond adequate glycemic control, in particular
addressing weight, blood pressure and other contributors to cardiovascular
disease. In addition, the progressive nature of type 2 diabetes mellitus demands
the intensification and combination of glucose lowering therapies. In many
patients, there is a clinical inertia for the initiation of insulin therapy,
leading to failure in reaching glycemic targets in many patients. AREAS COVERED:
Recently a fixed-ratio combination therapy of the basal insulin degludec and the
glucagon-like peptide-1 analogue liraglutide has been developed and approved by
the EMA. The rationale for this combination, as well as an overview of the
published phase III clinical trials (DUAL I,II,V), are covered, highlighting the
most important conclusions. EXPERT OPINION: The combination therapy of insulin
degludec and liraglutide is an attractive therapeutic strategy in patients with
type 2 diabetes mellitus as it gives a robust glycemic control with a low risk
for hypoglycemia and less weight gain or even weight loss. The fixed-ratio
combination of insulin degludec and liraglutide offers a smart therapeutic
strategy in patients with type 2 diabetes mellitus where basal insulin needs to
be initiated or intensified.
PMID- 27484311
TI - Dynamics Correlation Network for Allosteric Switching of PreQ1 Riboswitch.
AB - Riboswitches are a class of metabolism control elements mostly found in bacteria.
Due to their fundamental importance in bacteria gene regulation, riboswitches
have been proposed as antibacterial drug targets. Prequeuosine (preQ1) is the
last free precursor in the biosynthetic pathway of queuosine that is crucial for
translation efficiency and fidelity. However, the regulation mechanism for the
preQ1 riboswitch remains unclear. Here we constructed fluctuation correlation
network based on all-atom molecular dynamics simulations to reveal the regulation
mechanism. The results suggest that the correlation network in the bound
riboswitch is distinctly different from that in the apo riboswitch. The community
network indicates that the information freely transfers from the binding site of
preQ1 to the expression platform of the P3 helix in the bound riboswitch and the
P3 helix is a bottleneck in the apo riboswitch. Thus, a hypothesis of "preQ1
binding induced allosteric switching" is proposed to link riboswitch and
translation regulation. The community networks of mutants support this
hypothesis. Finally, a possible allosteric pathway of A50-A51-A52-U10-A11-G12-G56
was also identified based on the shortest path algorithm and confirmed by
mutations and network perturbation. The novel fluctuation network analysis method
can be used as a general strategy in studies of riboswitch structure-function
relationship.
PMID- 27484312
TI - Frontotemporal dementia and language networks: cortical thickness reduction is
driven by dyslexia susceptibility genes.
AB - Variations within genes associated with dyslexia result in a language network
vulnerability, and in patients with Frontotemporal Dementia (FTD), language
disturbances represent a disease core feature. Here we explored whether
variations within three related-dyslexia genes, namely KIAA0319, DCDC2, and
CNTNAP, might affect cortical thickness measures in FTD patients. 112 FTD
patients underwent clinical and neuropsychological examination, genetic analyses
and brain Magnetic Resonance Imaging (MRI). KIAA0319 rs17243157 G/A, DCDC2
rs793842 A/G and CNTNAP2 rs17236239 A/G genetic variations were assessed.
Cortical thickness was analysed by Freesurfer. Patients carrying KIAA0319 A*(AG
or AA) carriers showed greater cortical thickness atrophy in the left fusiform
and inferior temporal gyri, compared to KIAA0319 GG (p <= 0.001). Patients
carrying CNTNAP2 G*(GA or GG) showed reduced cortical thickness in the left
insula thenCNTNAP2 AA carriers (p<=0.001). When patients with both at-risk
polymorphisms were considered (KIAA0319 A* and CNTNAP2 G*), greater and addictive
cortical thickness atrophy of the left insula and the inferior temporal gyrus was
demonstrated (p <= 0.001). No significant effect of DCDC2 was found. In FTD,
variations of KIAA0319 and CNTNAP2 genes were related to cortical thickness
abnormalities in those brain areas involved in language abilities. These findings
shed light on genetic predisposition in defining phenotypic variability in FTD.
PMID- 27484313
TI - CCR4 and CAF1 deadenylases have an intrinsic activity to remove the post-poly(A)
sequence.
AB - MicroRNAs (miRNAs) recruit the CCR4-NOT complex, which contains two deadenylases,
CCR4 and CAF1, to promote shortening of the poly(A) tail. Although both CCR4 and
CAF1 generally have a strong preference for poly(A) RNA substrates, it has been
reported from yeast to humans that they can also remove non-A residues in vitro
to various degrees. However, it remains unknown how CCR4 and CAF1 remove non-A
sequences. Herein we show that Drosophila miRNAs can promote the removal of 3'
terminal non-A residues in an exonucleolytic manner, but only if an upstream
poly(A) sequence exists. This non-A removing reaction is directly catalyzed by
both CCR4 and CAF1 and depends on the balance between the length of the internal
poly(A) sequence and that of the downstream non-A sequence. These results suggest
that the CCR4-NOT complex has an intrinsic activity to remove the 3'-terminal non
A modifications downstream from the poly(A) tail.
PMID- 27484316
TI - Proteomic analysis of the effects of CSF-1 and IL-1alpha on dental follicle
cells.
AB - Tooth eruption is a complex physiological process involving both osteogenesis and
bone resorption. Signals from the dental follicle (DF) regulate bone remodeling
during tooth eruption. Interleukin-1alpha (IL-1alpha) may be the initial promoter
of tooth eruption, whereas colony-stimulating factor-1 (CSF-1) may attract
monocytes into the DF and stimulate osteoclast differentiation. In the present
study, differential proteomics was employed to explore protein changes in rat DF
cells (DFCs) under the effects of CSF-1 and IL-1alpha. A total of 47 protein
spots were differentially expressed in rat DFCs, and 40 protein spots were
identified by MALDI-TOF-MS. The identified proteins were grouped into functional
categories including cytoskeletal proteins, metal-binding proteins, proteins
involved in secretion and degradation, cell cycle proteins and stress proteins.
In IL-1alpha-induced rat DFCs, 31 proteins were upregulated compared with the
control and included heat shock protein beta-1 (HSP25, also known as
HSP27/HSPbeta1), vimentin, TMEM43, the GTP-binding protein Rab-3D, 6-pyruvoyl
tetrahydrobiopterin synthase and actin. In total, 7 proteins were downregulated,
including serum albumin, GIPC1, DNA primase large subunit, cullin-5 and cyclin
G1. In CSF-1-induced rat DFCs, 3 proteins were upregulated and 7 proteins were
downregulated when compared with the controls. The upregulated proteins included
the GTP-binding protein Rab-3D and alpha-actin. The downregulated proteins
included cullin-5, serum albumin, PDZ domain-containing protein and cyclin-G1.
The differential expression of vimentin, actin, HSP25 and Rab-3D was verified by
western blotting and reverse transcription-quantitative polymerase chain reaction
analyses. The present findings provide an insight into the mechanisms involved in
tooth eruption.
PMID- 27484317
TI - Left Ventricular Mechanics in Untrained and Trained Males with Tetraplegia.
AB - Reduced left ventricular (LV) function is common in tetraplegia, yet it is
unknown whether intrinsic myocardial function is attenuated. This study examined
the effect of SCI and exercise-training status on LV mechanics (intrinsic
function) and LV systolic/diastolic function by comparing untrained (UT) and
trained (TT) individuals with tetraplegia and able-bodied (AB) individuals.
Individuals with tetraplegia had a traumatic, chronic, motor-complete cervical
spinal cord injury. Nine UT males (40 +/- 10 years), 8 TT males (30 +/- 5 years),
and nine AB males (37 +/- 9 years) participated in the study. LV indices were
assessed using two-dimensional transthoracic echocardiography, with speckle
tracking analysis for the determination of LV mechanics. For systolic function,
stroke volumes were lower in both UT (59 +/- 9 mL; p < 0.001) and TT (63 +/- 9
mL; p < 0.001) relative to AB (82 +/- 11 mL), whereas systolic mechanics were
similar across groups. Diastolic function was only reduced in UT, including a
lower ratio of early-to-late transmitral filling velocity (1.55 +/- 0.28)
relative to TT (2.07 +/- 0.42; p < 0.05) and AB (2.44 +/- 0.61; p < 0.01) and
longer isovolumetric relaxation times in UT (101 +/- 7 ms) relative to TT (88 +/-
11 ms; p < 0.05) and AB (85 +/- 6 ms; p < 0.01). Diastolic mechanics (apical
circumferential strain rate) were significantly enhanced in TT (3.03 +/- 0.83 s
1) compared to AB (1.85 +/- 0.65 s-1; p < 0.05). There was a trend (p = 0.062)
for a between-group difference in apical radial diastolic strain rate (UT: -2.51
+/- 0.83 s-1; TT: -3.92 +/- 1.96 s-1; AB: -1.84 +/- 0.46 s-1). In tetraplegia,
attenuated LV systolic function is not attributed to intrinsic dysfunction,
whereas exercise-training status appears to improve both global LV diastolic
function and LV mechanics.
PMID- 27484319
TI - Promoting Global Health - Prevention and Treatment of Substance Abuse and HIV in
Asia.
AB - This special issue contains 20 papers including 3 Perspectives, 1 Brief Report, 6
Invited Reviews, and 10 Original Articles, which highlight the work by presenters
at the second meeting of the biennial Conference Series to Promote Global Health
held on April 22-24, 2015 in Hangzhou, Zhejiang, China. These papers focused on
the prevalent substance misuse of amphetamine-type-stimulants and opioids, and
the increasing prevalence of HIV-infection in Asian countries. The Conference
Series is sponsored by the National Institute on Drug Abuse of the U.S. National
Institutes of Health, with the goal of exchanging knowledge and ideas related to,
and promoting international collaborative work on, the prevention and treatment
of substance use disorders and HIV-infection, in order to promote health in Asian
and Pacific Islanders and other populations.
PMID- 27484318
TI - Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human
Studies and Animal Models.
AB - Methamphetamine (Meth) use is frequent among HIV-infected persons. Combined HIV
and Meth insults may exacerbate neural injury in vulnerable neuroanatomic
structures or circuitries in the brain, leading to increased behavioral
disturbance and cognitive impairment. While acute and chronic effects of Meth in
humans and animal models have been studied for decades, the neurobehavioral
effects of Meth in the context of HIV infection are much less explored. In-depth
understanding of the scope of neurobehavioral phenotypes and mechanisms in
HIV/Meth intersection is needed. The present report summarizes published research
findings, as well as unpublished data, in humans and animal models with regard to
neurobehavioral disturbance, neuroimaging, and neuropathology, and in vitro
experimental systems, with an emphasis on findings emerging from the National
Institute on Drug Abuse (NIDA) funded Translational Methamphetamine AIDS Research
Center (TMARC). Results from human studies and animal (primarily HIV-1 gp120
transgenic mouse) models thus far suggest that combined HIV and Meth insults
increase the likelihood of neural injury in the brain. The neurobehavioral
effects include cognitive impairment and increased tendencies toward impaired
behavioral inhibition and social cognition. These impairments are relevant to
behaviors that affect personal and social risks, e.g. worse medication adherence,
riskier behaviors, and greater likelihood of HIV transmission. The underlying
mechanisms may include electrochemical changes in neuronal circuitries, injury to
white matter microstructures, synaptodendritic damage, and selective neuronal
loss. Utilization of research methodologies that are valid across species is
instrumental in generating new knowledge with clinical translational value.
PMID- 27484320
TI - Longer coronary anastomosis provides lower energy loss in coronary artery bypass
grafting.
AB - Distal anastomosis technique affects graft patency and long-term outcomes in
coronary artery bypass grafting, however, there is no standard for the
appropriate length of distal anastomosis. The purpose of this study is to
evaluate whether longer distal anastomosis provides higher quality of distal
anastomosis and better hemodynamic patterns. Off pump CABG training simulator,
YOUCAN (EBM Corporation, Japan), was used for distal anastomosis model. Two
lengths of distal anastomosis model (10 versus 4 mm) were prepared by end-to-side
anastomosis technique. After CT scan constructed three-dimensional inner shape of
distal anastomosis, computational flow dynamics (CFD) was used to analyze
hemodynamic patterns. The working flow was defined as Newtonian fluid with
density of 1050 kg/m3 and viscosity of 4 mPa s. The boundary condition was set to
100 mmHg at inlet, 50 ml/min at outlet, and 100 % stenosis of proximal coronary
artery. Three-dimensional CT imaging showed quality of distal anastomosis in 10
mm model was more uniform without vessel wall inversion or kinking compared to 4
mm model. Anastomotic flow area was significantly larger in 10 mm model than that
in 4 mm model (28.67 +/- 4.91 versus 8.89 +/- 3.18 mm2, p < 0.0001). Anastomotic
angle was significantly smaller in 10 mm model compared to 4 mm model (10.2 +/-
5.65 degrees versus 20.6 +/- 3.31 degrees , p < 0.0001). CFD analysis
demonstrated 10 mm model had streamlined flow with smooth graft curvature,
whereas 4 mm model had abrupt blood flow direction changes with flow separation
at the toe. 10 mm model had significantly lower energy loss than 4 mm model
(34.78 +/- 6.90 versus 77.10 +/- 21.47 MUW, p < 0.0001). Longer distal
anastomosis provided higher quality of distal anastomosis, larger anastomotic
flow area, smaller anastomotic angle, and smoother graft curvatures. These
factors yielded lower energy loss at distal anastomosis.
PMID- 27484321
TI - The impact of a simulated intervention on attitudes of undergraduate nursing and
medical students towards end of life care provision.
AB - BACKGROUND: The concerns of undergraduate nursing and medical students' regarding
end of life care are well documented. Many report feelings of emotional distress,
anxiety and a lack of preparation to provide care to patients at end of life and
their families. Evidence suggests that increased exposure to patients who are
dying and their families can improve attitudes toward end of life care. In the
absence of such clinical exposure, simulation provides experiential learning with
outcomes comparable to that of clinical practice. The aim of this study was
therefore to assess the impact of a simulated intervention on the attitudes of
undergraduate nursing and medical students towards end of life care. METHODS: A
pilot quasi-experimental, pretest-posttest design. Attitudes towards end of life
care were measured using the Frommelt Attitudes Towards Care of the Dying Part B
Scale which was administered pre and post a simulated clinical scenario. 19
undergraduate nursing and medical students were recruited from one large Higher
Education Institution in the United Kingdom. RESULTS: The results of this pilot
study confirm that a simulated end of life care intervention has a positive
impact on the attitudes of undergraduate nursing and medical students towards end
of life care (p < 0.001). CONCLUSIONS: Active, experiential learning in the form
of simulation teaching helps improve attitudes of undergraduate nursing and
medical students towards end of life. In the absence of clinical exposure,
simulation is a viable alternative to help prepare students for their
professional role regarding end of life care.
PMID- 27484322
TI - The Application of Standards and Recommendations to Clinical Ethics Consultation
in Practice: An Evaluation at German Hospitals.
AB - The executive board of the Academy for Ethics in Medicine (AEM) and two AEM
working groups formulated standards and recommendations for clinical ethics
consultation in 2010, 2011, and 2013. These guidelines comply with the
international standards like those set by the American Society for Bioethics and
Humanities. There is no empirical data available yet that could indicate whether
these standards and recommendations have been implemented in German hospitals.
This desideratum is addressed in the present study. We contacted 1.858 German
hospitals between September 2013 and January 2014. A follow-up survey was
conducted between October 2014 and January 2015. The data of the initial survey
and the follow-up survey were merged and evaluated. The statements of the
participants were compared with the standards and recommendations. The standards
of the AEM concerning the tasks of clinical ethics consultation (including ethics
consultation, ethics training and the establishment of policy guidelines) are
employed by a majority of participants of the study. Almost all of these
participants document their consultation activities by means of protocols or
entries in the patient file. There are deviations from the recommendations of the
AEM working groups regarding the drafting of statutes, activity reports, and
financial support. The activities of clinical ethics consultation predominantly
comply with the standards of the AEM and recommendations for the documentation.
The recommendations for evaluation should be improved in practice. This applies
particularly for activity reports in order to evaluate the activities. Internal
evaluation could take place accordingly.
PMID- 27484323
TI - Impact factors 2015; NHJ on the rise!
PMID- 27484324
TI - Assessment of mineral intake in the diets of Polish postmenopausal women in
relation to their BMI-the RAC-OST-POL study : Mineral intake in relation to BMI.
AB - BACKGROUND: The diets of postmenopausal women in Western countries tend to be
deficient in minerals, even if the energy value is at the recommended level. The
objective of the presented population-based cohort study was to assess the intake
of minerals (sodium, potassium, calcium, phosphorus, magnesium, iron, zinc and
copper) in the diets of women aged above 55 years and to analyse the relations
between BMI and mineral intake in this group. METHODS: The study was conducted in
a group of 406 women who were randomly recruited from the general population of
those aged above 55 years. The main outcome measures included BMI, reported
sodium, potassium, calcium, phosphorus, magnesium, iron, zinc and copper intake
assessed by dietary record (conducted during two typical, non-consecutive days).
The distribution was verified with the use of the Shapiro-Wilk test. The
comparison between groups was conducted using ANOVA with the LSD post hoc test or
Kruskal-Wallis ANOVA with multiple comparisons. A comparison of satisfying
nutritional needs was conducted using the chi-square test. RESULTS: Normal body
weight individuals were characterised by lower sodium intake per 1000 kcal of
diet than obese class II and III individuals (BMI >= 35.0 kg/m(2)). Overweight
individuals were characterised by lower potassium and magnesium intake per 1000
kcal of diet than obese class I individuals (BMIepsilon < 30.0; 35.0 kg/m(2)).
The majority of individuals was characterised by insufficient potassium, calcium
and magnesium intake. No differences in satisfying nutritional needs between BMI
groups were observed for all minerals. CONCLUSIONS: Following an improperly
balanced diet was observed in the group of postmenopausal female individuals
analysed. It was stated that the daily intake of all the assessed minerals was
not BMI-dependent for the postmenopausal female individuals, but the nutrient
density of diet (for sodium, potassium and magnesium) was associated with BMI.
PMID- 27484325
TI - Intention to Use Long-Term Care Facilities: Differences beween Korean Pre-elderly
and Korean Baby-boomers.
AB - With the rapidly increasing number of older adults, dealing with long-term care
(LTC) needs becomes an emerging issue in South Korea. This study aims to examine
factors affecting the intention to use longtermcare facilities with two groups of
young-old adults: (1) Korean pre-elderly (KPE) and (2) Korean babyboomers (KBB).
Guided by Andersen's behavioral model of health service use and prior research,
predisposing characters, enabling resources, need factors, availabilities of
informal care and self-care activities were used as predictors. In the final
analyses, 803 KPE and 966 KBB were included. The results of logistic regression
analyses showed different findings in two groups. Age, education, spouse's
physicalhealth, and self-care activities for relationship with family and friends
are significantly associated with intention to use LTC facilities among KPE.
However, income, physical health of respondents, and relationship satisfaction
with children are significantly related to intention of use LTC facilities in the
group of KBB. This study suggests different LTC needs between KPE and KBB. Health
care professionals and policy makers need to consider such differences to provide
quality LTC care for them.
PMID- 27484327
TI - Base-controlled [3+3] cycloaddition of isoquinoline N-oxides with azaoxyallyl
cations.
AB - A base-controlled [3+3] cycloaddition reaction of isoquinoline N-oxides with
azaoxyallyl cations is developed. 1,11b-dihydro-[1,2,4]oxadiazino[3,2
a]isoquinolin-2(3H)-ones are obtained when isoquinoline N-oxides are treated with
alpha-halohydroxamates in the presence of sodium carbonate, while 2-(isoquinolin
1-yloxy)acetamides are unexpectedly produced when the base is changed to cesium
carbonate. This transformation proceeds through an azaoxyallyl cation generated
in situ from alpha-bromohydroxamate, and the [3+3] cycloaddition reaction is the
key step for the final outcome.
PMID- 27484326
TI - Socioeconomic Status, Health Behaviors, Obesity and Self-Rated Health among Older
Arabs in Israel.
AB - Socioeconomic inequalities in health are well documented. Recently, researchers
have shown interest in exploring the mechanisms by which measures of SES operate
through it to impact SRH, such as material, psychosocial and behavioral factors.
To examine the relationships between SES indicators and self-rated health (SRH);
and to determine whether health behaviors and obesity mediate the association
between SES indicators and SRH. A secondary analysis of data previously collected
through the third survey of socioeconomic and health status of the Arab
population in Israel, in which the SRH of 878 Arab-Israelis age 50 or older were
analyzed using logistic regression. The results showed that higher education
level and current employment in old age are associated with better SRH. However,
neither subjective economic status nor family income was associated with SRH.
Greater physical activity was found to be related to good?very good SRH, while
obesity was associated with less than good SRH. Finally, health behaviors
(physical activity) and obesity were revealed as mediators between SES indicators
(education and employment status) and SRH. The results highlight the importance
of high education level and employment status in old age to reduce health
inequalities. The findings also show that the relationship between SES and SRH
can operate through behavioral mechanisms (i.e., physical activity) and their
consequences (i.e., obesity), that can, however, be changed in old age.
PMID- 27484329
TI - Narratives of Stress in Health Meanings of African Americans in Lake County,
Indiana.
AB - Across the life course, African Americans bear an unequal burden of disease
compared to other racial groups. In spite of the widespread acknowledgment of
racial health disparities, the voices of African Americans, their articulations
of health and their local etiologies of health disparities are limited. In this
article, we highlight the important role of communication scholarship to
understand the everyday enactment of health disparities. Drawing upon the culture
centered approach (CCA) to co-construct narratives of health with African
Americans residents of Lake County, Indiana, we explore the presence of stress in
the everyday narratives of health. These narratives voice the social and
structural sources of stress, and articulate resistive coping strategies embedded
in relationship to structures.
PMID- 27484328
TI - Canine babesiosis and tick activity monitored using companion animal electronic
health records in the UK.
AB - Recent publications highlighting autochthonous Babesia canis infection in dogs
from Essex that have not travelled outside the UK are a powerful reminder of the
potential for pathogen emergence in new populations. Here the authors use
electronic health data collected from two diagnostic laboratories and a network
of 392 veterinary premises to describe canine Babesia cases and levels of Babesia
concern from January 2015 to March 2016, and the activity of ticks during
December 2015-March 2016. In most areas of the UK, Babesia diagnosis in this
population was rare and sporadic. In addition, there was a clear focus of Babesia
cases in the affected area in Essex. Until February 2016, analysis of health
records indicated only sporadic interest in Babesia largely in animals coming
from overseas. Following media coverage in March 2016, there was a spike in owner
concern that was geographically dispersed beyond the at-risk area. Tick activity
(identified as ticks being removed from animals in veterinary consultations) was
consistent but low during the period preceding the infections (<5 ticks/10,000
consultations), but increased in March. This highlights the use of electronic
health data to describe rapidly evolving risk and concern that follows the
emergence of a pathogen.
PMID- 27484330
TI - The Safety and Efficacy of Weekly Paclitaxel Administration for Anaplastic
Thyroid Cancer Patients: A Nationwide Prospective Study.
AB - BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive
malignancy, with a median survival of less than 6 months due to rapid progression
and resistance to multimodal therapies. Effective treatment strategies have not
been identified. A prospective clinical study was performed to objectively
evaluate outcomes of treatment with paclitaxel. METHODS: An investigator
initiated, multicenter, nonrandomized, open-label, single-arm study to evaluate
the feasibility and efficacy of weekly paclitaxel (80 mg/m(2)) administration for
patients with pathologically confirmed ATC was conducted in a nationwide
organization. RESULTS: Feasibility was analyzed in 56 patients. More than one
course of treatment was performed in 52 (93%) patients retaining sufficient dose
intensity (>84%). No patient had to terminate the treatment because of an adverse
event. The median overall survival was 6.7 months [confidence interval 4.4-9.0].
The 6-month survival was 54%. Among the 42 patients with an evaluable lesion,
none demonstrated complete remission, 9 (21%) showed partial remission, 22 (52%)
achieved stable disease, and 8 (19%) exhibited progressive disease; 3 did not
complete the initial treatment course. The objective response rate was 21%, and
the clinical benefit rate was 73%. The median time to progression was 1.6 months.
Statistically, no additional effect of concomitant radiation was demonstrated in
6 patients receiving combined therapy. Eight patients, in whom a complete post
treatment surgical removal of the tumor was feasible, survived significantly
longer (median 7.6 months [CI 8.1-23.0]) than the other 34 patients in whom the
tumor could not be completely removed after chemotherapy (5.4 months [CI 3.0
7.8], p = 0.018). SUMMARY: The study demonstrates objective and accurate
information concerning the feasibility and efficacy of a standardized treatment
with weekly paclitaxel administration for ATC patients. CONCLUSIONS: Weekly
paclitaxel administration for ATC patients can be of clinical benefit in a neo
adjuvant setting.
PMID- 27484331
TI - The effect of melatonin and vitamin C treatment on the experimentally induced
tympanosclerosis: study in rats.
AB - INTRODUCTION: The ethiopathogenesis of tympanosclerosis has not been completely
under- stood yet. Recent studies have shown that free oxygen radicals are
important in the formation of tympanosclerosis. Melatonin and Vitamin C are known
to be a powerful antioxidant, interacts directly with Reactive Oxygen Species and
controls free radical-mediated tissue damage. OBJECTIVE: To demonstrate the
possible preventative effects of melatonin and Vitamin C on tympanosclerosis in
rats by using histopathology and determination of total antioxidant status total
antioxidant status. METHODS: Standard myringotomy and standard injury were
performed in the middle ear of 24 rats. The animals were divided into three
groups: Group 1 received melatonin, Group 2 received vitamin C, and Group 3
received saline solution. RESULTS: The mean values of total antioxidant status
were similar in the all study groups before the treatment period. The mean values
of total antioxidant status were significantly higher in the melatonin and
vitamin C groups compared to control group but vitamin C with melatonin groups
were similar after the treatment period (p<0.001). Minimum and maximum wall
thicknesses were lower in the melatonin and vitamin C groups compared to the
control group but the differences were insignificant. CONCLUSION: Melatonin
increases total antioxidant status level and might have some effect on
tympanosclerosis that develops after myringotomy.
PMID- 27484332
TI - Characterization of interactions of simvastatin, pravastatin, fluvastatin, and
pitavastatin with bovine serum albumin: multiple spectroscopic and molecular
docking.
AB - The binding interactions of simvastatin (SIM), pravastatin (PRA), fluvastatin
(FLU), and pitavastatin (PIT) with bovine serum albumin (BSA) were investigated
for determining the affinity of four statins with BSA through multiple
spectroscopic and molecular docking methods. The experimental results showed that
SIM, PRA, FLU, and PIT statins quenched the intrinsic fluorescence of BSA through
a static quenching process and the stable stains-BSA complexes with the binding
constants in the order of 104 M-1 at 298 K were formed through intermolecular
nonbond interaction. The values of DeltaH0, DeltaS0 and DeltaG0 in the binding
process of SIM, PRA, FLU, and PIT with BSA were negative at the studied
temperature range, suggesting that the binding process of four statins and BSA
was spontaneous and the main interaction forces were van der Waals force and
hydrogen-bonding interactions. Moreover, the binding of four statins with BSA was
enthalpy-driven process due to |DeltaH degrees |>|TDeltaS degrees | under the
studied temperature range. From the results of site marker competitive
experiments and molecular docking, subdomain IIIA (site II) was the primary
binding site for SIM, PRA, FLU, and PIT on BSA. The results of UV-vis absorption,
synchronous fluorescence, 3D fluorescence and FT-IR spectra proved that the
slight change in the conformation of BSA, while the significant changes in the
conformation of SIM, PRA, FLU, and PIT drug in statin-BSA complexes, indicating
that the flexibility of statin molecules plays an important role in increasing
the stability of statin-BSA complexes.
PMID- 27484333
TI - Magnetic field effects of photocarrier generation in bulk heterojunctions at low
temperature.
AB - We report an experimental investigation of the magnetic field effect (MFE) in
polymer bulk heterojunction devices at temperatures below 10 K using photocarrier
extraction by linearly increasing voltages. The examined devices were composed of
an active layer of poly(3-hexylthiophene) and [6,6]-phenyl-C61-butyric acid
methyl ester. In the experiments, the delay time (td) dependence of the MFE was
investigated in detail. For td < 80 MUs, a positive MFE was observed in the field
region B < 0.1 T and a negative MFE was observed for B > 0.2 T. For td > 8 ms,
only a positive MFE proportional to B2 was observed. For the photocurrent pulse
detected immediately after light irradiation, the MFE was negligibly small. In a
high magnetic field of 15 T, a significant MFE exceeding 80% was observed at 1.8
K for td = 800 ms. We discuss the results based on a model of triplet-singlet (or
singlet-triplet) conversion in the magnetic field and estimate the exchange
integral for the charge-transfer exciton in this photovoltaic cell.
PMID- 27484334
TI - Statistical analysis plan for the PlAtelet Transfusion in Cerebral Haemorrhage
(PATCH) trial: a multicentre randomised controlled trial.
AB - BACKGROUND: Use of antiplatelet therapy shortly before stroke due to spontaneous
primary intracerebral haemorrhage (ICH) is associated with higher case fatality
in comparison to ICH without prior antithrombotic drug use. The PlAtelet
Transfusion in Cerebral Haemorrhage (PATCH) trial aimed to assess the effect of
platelet transfusion in patients presenting with ICH while using antiplatelet
therapy. The main hypothesis of PATCH was that platelet transfusion would reduce
death or dependence by reducing ICH growth. METHODS/DESIGN: PATCH was a
multicentre prospective, randomised, open, blinded endpoint (PROBE) parallel
group trial, conducted at 60 hospitals in The Netherlands, Scotland and France.
Forty-one sites enrolled 190 patients with spontaneous supratentorial ICH aged
>=18 years, who had used antiplatelet therapy for >=7 days preceding ICH, if
Glasgow Coma Scale was >=8. Participants were randomised (1:1, with a secure web
based system using permuted blocks, stratified by study centre and type of
antiplatelet therapy pre-ICH) to receive either platelet transfusion within 6
hours of symptom onset and 90 minutes of diagnostic brain imaging, or standard
care without platelet transfusion. The primary outcome was modified Rankin Scale
(mRS) score assessed blind to treatment allocation at 3 months after ICH. Planned
secondary outcomes included ICH growth on brain imaging performed approximately
24 hours after randomisation, survival at 3 months, disability at 3 months scored
using the Amsterdam Medical Centre linear disability score, heterogeneity of
treatment effect on mRS and ICH growth according to presence of the computed
tomography angiography spot sign, causes of poor outcome, and cost-effectiveness.
Safety outcomes were transfusion reactions, thromboembolic complications, and
serious adverse events occurring during hospitalisation. This statistical
analysis plan was written without knowledge of the unblinded data. TRIAL
REGISTRATION: The trial was registered with the Netherlands Trial Register on 29
April 2008 ( NTR1303 ).
PMID- 27484335
TI - 1,3,4-Thiadiazole derivatives of R-(+)-limonene benzaldehyde-thiosemicarbazones
cause death in Trypanosoma cruzi through oxidative stress.
AB - This work evaluated the in vitro and in vivo activity of TDZ 2 on Trypanosoma
cruzi amastigotes and determined the possible mechanism of action of this
compound on T. cruzi death. TDZ 2 inhibited T. cruzi proliferation in vitro and
had low haemolytic potential. It also induced morphological and ultrastructural
alterations. We observed a reduction of cell volume, the depolarization of the
mitochondrial membrane, an increase in ROS production, lipoperoxidation of the
cell membrane, lipid bodies formation and production of nitric oxide, a decrease
in reduced thiols levels and, presence of autophagic vacuoles. The in vivo study
found a reduction of parasitemia in animals treated with TDZ 2 alone or combined
with benznidazole. Altogether, the alterations induced by TDZ 2 point to an
oxidative stress condition that lead to T. cruzi cell death.
PMID- 27484336
TI - Development of sedentary behavior across childhood and adolescence: longitudinal
analysis of the Gateshead Millennium Study.
AB - BACKGROUND: In many parts of the world policy and research interventions to
modify sedentary behavior of children and adolescents are now being developed.
However, the evidence to inform these interventions (e.g. how sedentary behavior
changes across childhood and adolescence) is limited. This study aimed to assess
longitudinal changes in sedentary behavior, and examine the degree of tracking of
sedentary behavior from age 7y to 15y. METHODS: Participants were part of the
Gateshead Millennium Study cohort. Measures were made at age 7y (n = 507), 9y (n
= 510), 12y (n = 425) and 15y (n = 310). Participants were asked to wear an
ActiGraph GT1M and accelerometer epochs were defined as sedentary when recorded
counts were <=25 counts/15 s. Differences in sedentary time and sedentary
fragmentation were examined using the Friedman test. Tracking was examined using
Spearman's correlation coefficients and trajectories over time were assessed
using multilevel linear spline modelling. RESULTS: Median daily sedentary time
increased from 51.3% of waking hours at 7y to 74.2% at 15y. Sedentary
fragmentation decreased from 7y to 15y. The median number of breaks/hour
decreased from 8.6 to 4.1 breaks/hour and the median bout duration at 50% of the
cumulative sedentary time increased from 2.4 min to 6.4 min from 7y to 15y.
Tracking of sedentary time and sedentary fragmentation was moderate from 7y to
15y however, the rate of change differed with the steepest increases/decreases
seen between 9y and 12y. CONCLUSION: In this study, sedentary time was high and
increased to almost 75% of waking hours at 15y. Sedentary behavior became
substantially less fragmented as children grew older. The largest changes in
sedentary time and sedentary fragmentation occurred between 9y to 12y, a period
which spans the transition to secondary school. These results can be used to
inform future interventions aiming to change sedentary behavior.
PMID- 27484338
TI - Boolean network identification from perturbation time series data combining
dynamics abstraction and logic programming.
AB - Boolean networks (and more general logic models) are useful frameworks to study
signal transduction across multiple pathways. Logic models can be learned from a
prior knowledge network structure and multiplex phosphoproteomics data. However,
most efficient and scalable training methods focus on the comparison of two time
points and assume that the system has reached an early steady state. In this
paper, we generalize such a learning procedure to take into account the time
series traces of phosphoproteomics data in order to discriminate Boolean networks
according to their transient dynamics. To that end, we identify a necessary
condition that must be satisfied by the dynamics of a Boolean network to be
consistent with a discretized time series trace. Based on this condition, we use
Answer Set Programming to compute an over-approximation of the set of Boolean
networks which fit best with experimental data and provide the corresponding
encodings. Combined with model-checking approaches, we end up with a global
learning algorithm. Our approach is able to learn logic models with a true
positive rate higher than 78% in two case studies of mammalian signaling
networks; for a larger case study, our method provides optimal answers after 7min
of computation. We quantified the gain in our method predictions precision
compared to learning approaches based on static data. Finally, as an application,
our method proposes erroneous time-points in the time series data with respect to
the optimal learned logic models.
PMID- 27484337
TI - Periodic mechanical stress induces the extracellular matrix expression and
migration of rat nucleus pulposus cells by upregulating the expression of
intergrin alpha1 and phosphorylation of downstream phospholipase Cgamma1.
AB - Intervertebral disk degeneration (IDD) is a major cause of low back pain and an
important socioeconomic burden. Degradation of the extracellular matrix (ECM) of
nucleus pulposus (NP) cells in the interverterbal disk is important for IDD.
Stress of a suitable frequency and amplitude promotes the synthesis of the ECM of
NP cells, however, the associated mechanisms remain to be fully elucidated The
present study aimed to investigate the effect of integrin alpha1 on the migration
and ECM synthesis of NP cells under soft periodic mechanical stress. Rat NP cells
were isolated and plated onto slides, and were then treated with or without the
use of a periodic mechanical stress system. The expression levels of integrin
alpha1, alpha5 and alphav, ECM collagen 2A1 (Col2A1) and aggrecan, and the
phosphorylation of phospholipase C-gamma1 (PLCgamma1) were measured using reverse
transcription-quantitative polymerase chain reaction and western blot analyses.
Cell migration was assayed using a scratch experiment. The results showed that
exposure to periodic mechanical stress significantly induced the mRNA expression
levels of Col2A1 and aggrecan, cell migration, mRNA expression of integrin alpha1
and phosphorylation of PLC-gamma1 of the NP, compared with the control (P<0.05).
Inhibition of the PLCgamma1 protein by U73122 significantly decreased the ECM
expression under periodic mechanical stress (P<0.05). Small interfering RNA
mediated integrin alpha1 gene knockdown suppressed the mRNA expression levels of
Col2A1 and aggrecan, and suppressed the migration and phosphorylation of
PLCgamma1 of the NP cells under periodic mechanical stress, compared with the
control (P<0.05). In conclusion, periodic mechanical stress induced ECM
expression and the migration of NP cells via upregulating the expression of
integrin alpha1 and the phosphorylation of downstream PLCgamma1. These findings
provide novel information to aid the understanding of the pathogenesis and
development of IDD.
PMID- 27484340
TI - Total Synthesis of (-)-Carinatine A and (+)-Lycopladine A.
AB - An efficient synthesis of two Lycopodium alkaloids, (-)-carinatine A and (+)
lycopladine A, is achieved in eight steps. The synthesis features an
intramolecular aldol reaction for assembling the 6,5-fused ring system, a
subsequent Tsuji-Trost allylation for generating a quarternary carbon center, and
a 6pi-electrocyclization to form the pyridine ring.
PMID- 27484339
TI - Effects of remifentanil and remifentanil-alfentanil administration on emergence
agitation after brief ophthalmic surgery in children.
AB - BACKGROUND: Sevoflurane is commonly usedin pediatric anesthesia due to its non
irritating airway properties, and rapid induction and emergence. However, it is
associated with emergence agitation (EA) in children. EA may cause injury to the
child or damage to the surgical site and is a cause of stress to both caregivers
and families. The efficacy of remifentanil and additional alfentanil on EA in the
pediatric patients underwent ophthalmic surgery with sevofluraneanesthesiawas not
well evaluated to date. This study was designed to compare the effects of
remifentanil and remifentanil plus alfentanil on EA in children undergoing
ophthalmic surgery with sevofluraneanesthesia. METHODS: Children (aged 3-9 years)
undergoing ophthalmic surgery undersevoflurane anesthesia were randomly assigned
to group S (sevoflurane alone), group R (sevofluraneandremifentanil infusion, 0.1
MUg/kg/min), or group RA (sevoflurane withremifentanil infusion and intravenous
injection of alfentanil 5 MUg/kg 10 min before the end of surgery). Mean arterial
pressure (MAP), heart rate (HR), and sevoflurane concentration were checked every
15 min after induction of anesthesia. The incidence of EA, time to extubation
from discontinuation of sevoflurane inhalation, and time to discharge from the
postanesthesia care unit was assessed. RESULTS: The incidence of EA was
significantly lower in groups R (32 %, 11/34; P = 0.01) and RA (31 %, 11/35; P =
0.008) than group S (64 %, 21/33). The time to extubation was prolonged in group
RA (11.2 +/- 2.3 min; P = 0.004 and P = 0.016) compared with groups S (9.2 +/-
2.3 min) andR (9.5 +/- 2.4 min). MAP and HR were similar in all three groups,
apart from a reduction in HR at 45 min in groups R and RA. However, the
sevoflurane concentration was lower in groups R and RA than group S (P < 0.001).
CONCLUSIONS: The administration of remifentanil to children undergoing ophthalmic
surgery undersevoflurane anesthesia reduced the incidence of EA without
clinically significant hemodynamic changes. However, the addition of alfentanil(5
MUg/kg)10 min before the end of surgery provided no additional benefit compared
withremifentanil alone. TRIAL REGISTRATION: CLINICAL TRIAL NUMBER: NCT02486926 ,
June.29.2015.
PMID- 27484341
TI - Visually Induced Inhibition of Return Affects the Integration of Auditory and
Visual Information.
AB - Multisensory integration (MSI) and exogenous spatial attention can both speedup
responses to perceptual events. Recently, it has been shown that audiovisual
integration at exogenously attended locations is reduced relative to unattended
locations. This effect was observed at short cue-target intervals (200-250 ms).
At longer intervals, however, the initial benefits of exogenous shifts of spatial
attention at the cued location are often replaced by response time (RT) costs
(also known as Inhibition of Return, IOR). Given these opposing cueing effects at
shorter versus longer intervals, we decided to investigate whether MSI would also
be affected by IOR. Uninformative exogenous visual spatial cues were presented
between 350 and 450 ms prior to the onset of auditory, visual, and audiovisual
targets. As expected, IOR was observed for visual targets (invalid cue RT < valid
cue RT). For auditory and audiovisual targets, neither IOR nor any spatial cueing
effects were observed. The amount of relative multisensory response enhancement
and race model inequality violation was larger for uncued as compared with cued
locations indicating that IOR reduces MSI. The results are discussed in the
context of changes in unisensory signal strength at cued as compared with uncued
locations.
PMID- 27484342
TI - Comparative Transcriptomic Analysis of the Response of Dunaliella acidophila
(Chlorophyta) to Short-Term Cadmium and Chronic Natural Metal-Rich Water
Exposures.
AB - Heavy metals are toxic compounds known to cause multiple and severe cellular
damage. However, acidophilic extremophiles are able to cope with very high
concentrations of heavy metals. This study investigated the stress response under
natural environmental heavy metal concentrations in an acidophilic Dunaliella
acidophila. We employed Illumina sequencing for a de novo transcriptome assembly
and to identify changes in response to high cadmium concentrations and natural
metal-rich water. The photosynthetic performance was also estimated by pulse
amplitude-modulated (PAM) fluorescence. Transcriptomic analysis highlights a
number of processes mainly related to a high constitutive expression of genes
involved in oxidative stress and response to reactive oxygen species (ROS), even
in the absence of heavy metals. Photosynthetic activity seems to be unaltered
under short-term exposition to Cd and chronic exposure to natural metal-rich
water, probably due to an increase in the synthesis of structural photosynthetic
components preserving their functional integrity. An overrepresentation of Gene
Ontology (GO) terms related to metabolic activities, transcription, and
proteosomal catabolic process was observed when D. acidophila grew under chronic
exposure to natural metal-rich water. GO terms involved in carbohydrate metabolic
process, reticulum endoplasmic and Golgi bodies, were also specifically
overrepresented in natural metal-rich water library suggesting an endoplasmic
reticulum stress response.
PMID- 27484343
TI - The Interplay Between Predation, Competition, and Nutrient Levels Influences the
Survival of Escherichia coli in Aquatic Environments.
AB - Nutrient levels, competition from autochthonous microorganisms, and protozoan
predation may all influence survival of fecal microorganisms as they transition
from the gastrointestinal tract to aquatic habitats. Although Escherichia coli is
an important indicator of waterborne pathogens, the effects of environmental
stressors on its survival in aquatic environments remain poorly understood. We
manipulated organic nutrient, predation, and competition levels in outdoor
microcosms containing natural river water, sediments, and microbial populations
to determine their relative contribution to E. coli survival. The activities of
predator (protozoa) and competitor (indigenous bacteria) populations were
inhibited by adding cycloheximide or kanamycin. We developed a statistical model
of E. coli density over time that fits with the data under all experimental
conditions. Predation and competition had significant negative effects on E. coli
survival, while higher nutrient levels increased survival. Among the main
effects, predation accounted for the greatest variation (40 %) compared with
nutrients (25 %) or competition (15 %). The highest nutrient level mitigated the
effect of predation on E. coli survival. Thus, elevated organic nutrients may
disproportionately enhance the survival of E. coli, and potentially that of other
enteric bacteria, in aquatic habitats.
PMID- 27484344
TI - Attitudes and barriers uncontrolled asthma in Spain. Abanico study.
PMID- 27484345
TI - Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced
osteoarthritic pain in rats.
AB - BACKGROUND: Osteoarthritis (OA) is a chronic progressive joint disease
characterized by advanced joint pain, subchondral bone sclerosis and articular
cartilage degeneration. Resveratrol has been shown to have anti-inflammatory,
cardioprotective and antioxidant properties and to inhibit platelet aggregation
and coagulation. However, the effects of resveratrol on OA have not been
examined. In this study, we investigate the protective effects of resveratrol on
monosodium iodoacetate (MIA)-induced OA through inhibition of cyclooxygenase (COX
2) and inducible nitric oxide synthase (iNOS) signaling pathway in a rat model.
METHODS: A single intra-articular injection of MIA was injected into rats for the
induction of OA. The mechanical, heat and cold hyperalgesia were measured at days
0, 7 and 14. The serum and synovial fluid levels of IL-1beta, IL-10 and TNF-alpha
and osteocalcin were measured by enzyme-linked immunosorbent assay. The mRNA and
protein expressions of IL-1beta, IL-10, TNF-alpha, Il-6, MMP-13 and COX-2 and
iNOS were determined by RT-PCR and western blot, respectively. Osteoarthritic
lesion in the knee joint was evaluated by histological analysis. RESULTS: MIA
injected rats treated with resveratrol at a dose of either 5 or 10mg/kg body
weight were significantly reduced hyperalgesia of mechanical, heat and cold and
increased the vertical and horizontal movements. Subsequently, MIA-injected rats
increased serum and synovial fluid levels of IL-1beta, IL-10, IL-6, TNF-alpha,
MMP-13 and osteoclastic activity marker, osteocalcin and its articular cartilage
mRNA and protein expressions. Further, MIA-injected rats increased COX-2 and iNOS
mRNA and protein expressions were decreased by resveratrol. The protective effect
of resveratrol was comparable to a reference drug, etoricoxib. The cartilage
damage induced by MIA were attenuated by resveratrol. CONCLUSIONS: Taken
together, resveratrol has the potential to improve MIA-induced cartilage damage
by inhibiting the levels and expressions of inflammatory mediators suggesting
that resveratrol may be a potential therapeutic agent for OA.
PMID- 27484346
TI - New effective azelaic acid liposomal gel formulation of enhanced pharmaceutical
bioavailability.
AB - Azelaic acid is a naturally occurring saturated C9-dicarboxylic acid which has
been shown to be effective in the treatment of comedonal acne and inflammatory
acne, as well as hiperpigmentary skin disorders. The aim of the present study is
to compare new developed liposomal hydrogel (lipogel) and commercially available
product in terms of the active substance-azelaic acid bioavailability. Topical
formulations were evaluated for physical parameters, such as pH measurement,
organoleptic evaluation and liposome size analysis in lipogel formulation. In
addition, studies were performed on in vitro antimicrobial preservation,
stability and accumulation in the stratum corneum according to guidelines
established by European Pharmacopoeia and International Conferences on
Harmonisation. The new formula for liposomal gel with azelaic acid has the
stability required for pharmaceutical preparations. Moreover, presented
formulation F2 reveals a very high accumulation (187.5MUg/cm2) of an active
substance in the stratum corneum, which results in opportunity to decrease of the
API content to 10% in comparison to a reference formula: commercially available
cream with 20% of azelaic acid. The study reveals that the final formula of
lipogel F2 with azelaic acid had acceptable physical parameters that showed that
they were compatible with the skin and in addition this formulation passed
stability studies. In vitro antimicrobial preservation studies showed that the
formulated lipogel F2 showed strong antibacterial activity; thus, no
preservatives were added to the final composition of the preparation. The present
study concludes that the formulated lipogel F2 with azelaic acid is stable,
efficient in antimicrobial preservation and reveals improved active substance
bioavailability.
PMID- 27484347
TI - The combined application of human adipose derived stem cells and Chondroitinase
ABC in treatment of a spinal cord injury model.
AB - BACKGROUND: Although stem cell therapy has become a major focus as a new option
for management of spinal cord injury (SCI), its effectiveness should be promoted.
In this study, we investigated the effects of co-administrating human adipose
derived stem cells (hADSCs) and Chondroitinase ABC (ChABC) in a rat model of
spinal cord injury. MATERIAL AND METHODS: hADSCs derived from superficial layer
of abdominal adipose tissue were used to treat a contusion-induced SCI. Animals
were randomly allocated to five equal groups including sham (only laminectomy),
SCI (SCI+vehicle injection), hADSCs (1*106 hADSCs/10MUl intra-spinal injection),
ChABC (10MUl of 100U/ml ChABC intra-spinal injection injection), and
hADSCs+ChABC. Basso, Beattie and Bresnahan tests were used to evaluate locomotor
function. 8weeks after treatment, cavity size, myelination, cell differentiation
(neuron and astrocyte), and chondroitin sulfate amount were analyzed. RESULTS:
hADSC transplanted animals, ChABC injected animals (P<0.001), and hADSC+ChABC
treated rats (P<0.001) displayed significant motor improvement compared to SCI
group. Combination therapy of hADSCs and ChABC led to greater locomotor recovery
compared to using hADSCs (P<0.001) or ChABC (P<0.01) alone. Spinal cords in the
combined and single therapy groups had cavities filled with myelinated areas and
less chondroitin sulfate content in comparison with the control group (P<0.001).
hADSCs expressed GFAP, B III tubulin and Map2. CONCLUSION: Combination therapy
with ChABC and hADSCs exhibits more significant functional recovery than single
therapy using either. This result may be applicable in selection of the best
therapeutic strategy for SCI.
PMID- 27484348
TI - Implementing shared decision making in federally qualified health centers, a
quasi-experimental design study: the Office-Guidelines Applied to Practice
(Office-GAP) program.
AB - BACKGROUND: Use of Shared Decision-Making (SDM) and Decision Aids (DAs) has been
encouraged but is not regularly implemented in primary care. The Office
Guidelines Applied to Practice (Office-GAP) intervention is an application of a
previous model revised to address guidelines based care for low-income
populations with diabetes and coronary heart disease (CHD). OBJECTIVE: To
evaluate Office-GAP Program feasibility and preliminary efficacy on medication
use, patient satisfaction with physician communication and confidence in decision
in low-income population with diabetes and coronary heart disease (CHD) in a
Federally Qualified Healthcare Center (FQHC). METHOD: Ninety-five patients
participated in an Office-GAP program. A quasi-experimental design study, over 6
months with 12-month follow-up. Office-GAP program integrates health literacy,
communication skills education for patients and physicians, patient/physician
decision support tools and SDM into routine care. MAIN MEASURES: 1)
Implementation rates of planned program elements 2) Patient satisfaction with
communication and confidence in decision, and 3) Medication prescription rates.
We used the GEE method for hierarchical logistic models, controlling for
confounding. RESULTS: Feasibility of the Office-GAP program in the FQHC setting
was established. We found significant increase in use of Aspirin/Plavix, statin
and beta-blocker during follow-up compared to baseline: Aspirin OR 1.5 (95 % CI:
1.1, 2.2) at 3-months, 1.9 (1.3, 2.9) at 6-months, and 1.8 (1.2, 2.8) at 12
months. Statin OR 1.1 (1.0, 1.3) at 3-months and 1.5 (1.1, 2.2) at 12-months;
beta-blocker 1.8 (1.1, 2.9) at 6-months and 12-months. Program elements were
consistently used (>= 98 % clinic attendance at training and tool used). Patient
satisfaction with communication and confidence in decision increased.
CONCLUSIONS: The use of Office-GAP program to teach SDM and use of DAs in real
time was demonstrated to be feasible in FQHCs. It has the potential to improve
satisfaction with physician communication and confidence in decisions and to
improve medication use. The Office-GAP program is a brief, efficient platform for
delivering patient and provider education in SDM and could serve as a model for
implementing guideline based care for all chronic diseases in outpatient clinical
settings. Further evaluation is needed to establish feasibility outside clinical
study, reach, effectiveness and cost-effectiveness of this approach.
PMID- 27484349
TI - Radiation recall gastritis secondary to combination of gemcitabine and erlotinib
in pancreatic cancer and response to PPI - a case report.
AB - BACKGROUND: Radiation recall gastritis is rare but can be induced after
concurrent chemoradiation for pancreatic cancer. We report a patient with
pancreatic cancer who developed radiation-recall gastritis related to a
combination of gemcitabine and erlotinib. CASE PRESENTATION: A 54-year-old female
with unresectable pancreatic cancer received gemcitabine in combination with
radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After
completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and
vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall
thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple
gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was
continued on maintenance chemotherapy. Two months later, the patient presented
with the similar symptoms and persistent gastric ulcers were observed during
subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI
therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine
and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan
and EGD at 6 months demonstrated resolution of the gastric ulcers. CONCLUSIONS:
Physicians should be aware of the possibility of radiation recall gastritis
associated with a combination of gemcitabine and erlotinib. Administration of
PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the
presence of radiation recall gastritis; however further studies are warranted.
PMID- 27484350
TI - Three siblings with familial non-medullary thyroid carcinoma: a case series.
AB - BACKGROUND: In 2015, thyroid carcinoma affected approximately 63,000 people in
the USA, yet it remains one of the most treatable cancers. It is mainly
classified into medullary and non-medullary types. Conventionally, medullary
carcinoma was associated with heritability but increasing reports have now begun
to associate non-medullary thyroid carcinoma with a genetic predisposition as
well. It is important to identify a possible familial association in patients
diagnosed with non-medullary thyroid carcinoma because these cancers behave more
destructively than would otherwise be expected. Therefore, it is important to
aggressively manage such patients and screening of close relatives might be
justified. Our case series presents a diagnosis of familial, non-syndromic, non
medullary carcinoma of the thyroid gland in three brothers diagnosed over a span
of 6 years. CASE PRESENTATIONS: We report the history, signs and symptoms,
laboratory results, imaging, and histopathology of the thyroid gland of three
Pakistani brothers of 58 years, 55 years, and 52 years from Sindh with non
medullary thyroid carcinoma. Only Patients 1 and 3 had active complaints of
swelling and pruritus, respectively, whereas Patient 2 was asymptomatic. Patients
2 and 3 had advanced disease at presentation with lymph node metastasis. All
patients underwent a total thyroidectomy with Patients 2 and 3 requiring a neck
dissection as well. No previous exposure to radiation was present in any of the
patients. Their mother had died from adrenal carcinoma but also had a swelling in
the front of her neck which was never investigated. All patients remained stable
at follow-up. CONCLUSIONS: Non-medullary thyroid carcinoma is classically
considered a sporadic condition. Our case report emphasizes a high index of
suspicion, a detailed family history, and screening of first degree relatives
when evaluating patients with non-medullary thyroid carcinoma to rule out
familial cases which might behave more aggressively.
PMID- 27484351
TI - Cohort of one million patients initiating antidepressant treatment in France: 12
month follow-up.
AB - AIMS: Previous studies have shown that the recommended minimum 6-month period for
antidepressant treatment is actually observed for only a minority of patients.
The objectives of this study were to characterise patients with newly prescribed
antidepressant treatment in France and identify factors possibly associated with
insufficient duration of treatment or the occurrence of certain events such as
sick leave, hospitalisations and suicide attempts. METHODS: Data were extracted
from the French health insurance database (SNIIRAM) and the national
hospitalisation database (PMSI) for patients covered by the main French health
insurance scheme representing 75% of the French population. Patients were
included if they had a newly prescribed antidepressant in 2011, but no prior
psychiatric diagnosis identified in the databases and no significant psychiatric
medication (such as antipsychotic or mood stabiliser) in 2009-2010. RESULTS: A
total of 998 710 patients (2% of the overall population), with a mean age of 50
years and 66% of females, initiated an antidepressant in 2011, which was
prescribed by a general practitioner in 89% of cases. Five generic names,
including three selective serotonin reuptake inhibitors, accounted for 75% of
first prescriptions. Only one reimbursement was observed for 40% of patients.
Treatment duration was less than 6 months for more than 80% of patients, more
frequently for low income earners, and varied according to age, gender and
region. The median time lag between first visit and antidepressant initiation was
27 days. Hospitalisation related to a psychiatric disease over the following 12
months was observed for 3% of patients. CONCLUSION: Duration of treatment and
follow-up were both insufficient for the majority of French patients initiating
antidepressant treatment in 2011, which may reflect poor quality of care for
people with mood or anxiety disorders, possibly because of overdiagnosis and
inappropriate drug treatment, or poor adherence and side effects, or poor follow
up.
PMID- 27484352
TI - Alkyltelluro Substitution Improves the Radical-Trapping Capacity of Aromatic
Amines.
AB - The synthesis of a variety of aromatic amines carrying an ortho-alkyltelluro
group is described. The new antioxidants quenched lipidperoxyl radicals much more
efficiently than alpha-tocopherol and were regenerable by aqueous-phase N
acetylcysteine in a two-phase peroxidation system. The inhibition time for diaryl
amine 9 b was four-fold longer than recorded with alpha-tocopherol. Thiol
consumption in the aqueous phase was found to correlate inversely to the
inhibition time and the availability of thiol is the limiting factor for the
duration of antioxidant protection. The proposed mechanism for quenching of
peroxyl radicals involves O-atom transfer from peroxyl to Te followed by H-atom
transfer from amine to alkoxyl radical in a solvent cage.
PMID- 27484353
TI - Neighborhood safety factors associated with older adults' health-related
outcomes: A systematic literature review.
AB - RATIONALE: Neighborhood safety is important for older adults' health and
wellbeing, but there has not been a synthesis in the literature of what is
currently known about this construct. OBJECTIVES: This systematic literature
review, following the PRISMA guidelines, focuses on identifying neighborhood
safety factors associated with health-related outcomes and behaviors of older
adults in the U.S. METHODS: A search was conducted in 2014 via Academic Search
Complete, CINAHL, Embase, MEDLINE, SportDis, and Transportation Databases. Based
on our inclusion and exclusion criteria, we identified thirty-two articles for
review. RESULTS: Sixteen studies examined health outcomes such as health status,
mental health, physical function, morbidity/mortality, and obesity; the other
sixteen studies focused on health behaviors, such as physical activity and
walking. Four domains of neighborhood safety were identified: overall/general
neighborhood safety; crime-related safety; traffic-related safety; and proxies
for safety (e.g., vandalism, graffiti). Overall/general neighborhood safety
appeared most relevant to mental health and physical function. Traffic-related
safety was most pertinent to physical activity, while crime-related safety was
more consistently associated with mental health and walking. While all safety
variables were significantly associated with mental health, no significant
associations were found for obesity. We also found that specific measures or
constructs of safety were not applied consistently across the examined studies,
making it difficult to compare the results. CONCLUSION: This review identified
several important gaps in the existing studies dealing with neighborhood safety
health relationships among older adults. Further studies are needed that examine
the different roles of multidimensional neighborhood safety in promoting the
community health, not only in the U.S., but globally.
PMID- 27484354
TI - Strengthening health disaster risk management in Africa: multi-sectoral and
people-centred approaches are required in the post-Hyogo Framework of Action era.
AB - BACKGROUND: In November 2012, the 62nd session of the Regional Committee for
Africa adopted a comprehensive 10-year regional strategy for health disaster risk
management (DRM). This was intended to operationalize the World Health
Organization's core commitments to health DRM and the Hyogo Framework for Action
2005-2015 in the health sectors of the 47 African member states. This study
reported the formative evaluation of the strategy, including evaluation of the
progress in achieving nine targets (expected to be achieved incrementally by
2014, 2017, and 2022). We proposed recommendations for accelerating the
strategy's implementation within the Sendai Framework for Disaster Risk
Reduction. METHODS: This study used a mixed methods design. A cross-sectional
quantitative survey was conducted along with a review of available reports and
information on the implementation of the strategy. A review meeting to discuss
and finalize the study findings was also conducted. RESULTS: In total, 58 % of
the countries assessed had established DRM coordination units within their
Ministry of Health (MOH). Most had dedicated MOH DRM staff (88 %) and national
level DRM committees (71 %). Only 14 (58 %) of the countries had health DRM
subcommittees using a multi-sectoral disaster risk reduction platform. Less than
40 % had conducted surveys such as disaster risk analysis, hospital safety index,
and mapping of health resources availability. Key challenges in implementing the
strategy were inadequate political will and commitment resulting in poor funding
for health DRM, weak health systems, and a dearth of scientific evidence on
mainstreaming DRM and disaster risk reduction in longer-term health system
development programs. CONCLUSIONS: Implementation of the strategy was behind
anticipated targets despite some positive outcomes, such as an increase in the
number of countries with health DRM incorporated in their national health
legislation, MOH DRM units, and functional health sub-committees within national
DRM committees. Health system-based, multi-sectoral, and people-centred
approaches are proposed to accelerate implementation of the strategy in the post
Hyogo Framework of Action era.
PMID- 27484355
TI - Coronary artery rupture in blunt thoracic trauma: a case report and review of
literature.
AB - BACKGROUND: Blunt thoracic trauma can rarely result in coronary artery injury.
Blunt trauma can result in occlusion of any of the coronary arteries or can lead
to its rupture and bleeding. Traumatic coronary artery occlusion can lead to
myocardial infarction, while its rupture and bleeding can result in
hemopericardium and cardiac tamponade, and can be rapidly fatal. Survival after
coronary artery rupture in blunt thoracic trauma is exceedingly rare. CASE
PRESENTATION: We present a case of a young male who sustained a blunt thoracic
trauma in a motor vehicle collision, that resulted in rupture of the left
anterior descending (LAD) coronary artery and subsequent cardiac tamponade.
Prompt surgical intervention with pericardiotomy and ligation of the artery has
resulted in survival of the patient. CONCLUSIONS: In cases of traumatic coronary
artery rupture, early surgical intervention is crucial to avoid mortality.
Ligation of the injured coronary is a viable option in selected cases, and can be
the most expeditious option in patients in extremis.
PMID- 27484357
TI - Mediterranean diet and nonalcoholic fatty liver disease: molecular mechanisms of
protection.
AB - Nutritional habits modifications have shown an important impact in preventing and
ameliorating metabolic alterations, such as nonalcoholic fatty liver disease
(NAFLD). Among several dietary approaches that exert positive effects in NAFLD
patients, the Mediterranean dietary pattern has shown notable benefits. This
review explores the molecular mechanisms through which the Mediterranean diet
would improve risk factors associated with metabolic syndrome and NAFLD. The main
features of the Mediterranean diet acting on metabolism are represented by its
whole-grain and low glycemic index cereal-based items, its fatty acid profile,
and its content in phytochemical compounds. Carbohydrate-rich foods high in
dietary fiber inducing low glycemic response are able to interact with glucose
and insulin metabolism. Unsaturated fatty acids are associated with better
hepatic lipid metabolism. Finally, phytochemical compounds, such as dietary
polyphenols, are thought to ameliorate inflammation, which is considered one of
the mechanisms through which NALFD may evolve into nonalcoholic steatohepatitis
(NASH).
PMID- 27484356
TI - Longitudinal study of computerized cardiotocography in early fetal growth
restriction.
AB - OBJECTIVES: To explore whether, in early fetal growth restriction (FGR), the
longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be
used to identify imminent fetal distress and whether abnormalities of FHR
recordings are associated with 2-year infant outcome. METHODS: The original
TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus
(DV) Doppler pulsatility index (PI), in combination with safety-net criteria of
very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could
improve 2-year infant survival without neurological impairment in comparison with
delivery based on CTG monitoring only. This was a secondary analysis of women who
delivered before 32 weeks and had consecutive STV data recorded > 3 days before
delivery and known infant outcome at 2 years of age. Women who received
corticosteroids within 3 days of delivery were excluded. Individual regression
line algorithms of all STV values, except the last one before delivery, were
calculated. Life tables and Cox regression analysis were used to calculate the
daily risk for low STV or very low STV and/or FHR decelerations (below DV group
safety-net criteria) and to assess which parameters were associated with this
risk. Furthermore, it was assessed whether STV pattern, last STV value or
recurrent FHR decelerations were associated with 2-year infant outcome. RESULTS:
One hundred and forty-nine women from the original TRUFFLE study met the
inclusion criteria. Using the individual STV regression lines, prediction of a
last STV below the cut-off used by the CTG monitoring group had sensitivity of
42% and specificity of 91%. For each day after study inclusion, the median risk
for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2-7%) and for
very low STV and/or recurrent FHR decelerations (below DV group safety-net
criteria) was 5% (IQR, 4-7%). Measures of STV pattern, fetal Doppler (arterial or
venous), birth-weight multiples of the median and gestational age did not
usefully improve daily risk prediction. There was no association of STV
regression coefficients, a low last STV and/or recurrent FHR decelerations with
short- or long-term infant outcomes. CONCLUSION: The TRUFFLE study showed that a
strategy of DV monitoring with safety-net criteria of very low STV and/or
recurrent FHR decelerations for delivery indication could increase 2-year infant
survival without neurological impairment. This post-hoc analysis demonstrates
that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group
safety-net criteria, is 5%, and that prediction is not possible. This supports
the rationale for CTG monitoring more often than daily in these high-risk
fetuses. Low STV and/or recurrent FHR decelerations were not associated with
adverse infant outcome and it appears safe to delay intervention until such
abnormalities occur, as long as DV-PI is within normal range. Copyright (c) 2016
ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27484358
TI - Non-monotonic temperature dependence of radiation defect dynamics in silicon
carbide.
AB - Understanding response of solids to particle irradiation remains a major
materials physics challenge. This applies even to SiC, which is a prototypical
nuclear ceramic and wide-band-gap semiconductor material. The lack of
predictability is largely related to the complex, dynamic nature of radiation
defect formation. Here, we use a novel pulsed-ion-beam method to study dynamic
annealing in 4H-SiC ion-bombarded in the temperature range of 25-250 degrees C.
We find that, while the defect recombination efficiency shows an expected
monotonic increase with increasing temperature, the defect lifetime exhibits a
non-monotonic temperature dependence with a maximum at ~100 degrees C. This
finding indicates a change in the dominant defect interaction mechanism at ~100
degrees C. The understanding of radiation defect dynamics may suggest new paths
to designing radiation-resistant materials.
PMID- 27484359
TI - Determination of haloacetic acids in water using layered double hydroxides as a
sorbent in dispersive solid-phase extraction followed by liquid chromatography
with tandem mass spectrometry.
AB - In the present study, highly efficient and simple dispersive solid-phase
extraction procedure for the determination of haloacetic acids in water samples
has been established. Three different types of layered double hydroxides were
synthesized and used as a sorbent in dispersive solid-phase extraction. Due to
the interesting behavior of layered double hydroxides in an acidic medium (pH?4),
the analyte elution step was not needed; the layered double hydroxides are simply
dissolved in acid immediately after extraction to release the analytes which are
then directly introduced into a liquid chromatography with tandem mass
spectrometry system for analysis. Several dispersive solid-phase extraction
parameters were optimized to increase the extraction efficiency of haloacetic
acids such as temperature, extraction time and pH. Under optimum conditions, good
linearity was achieved over the concentration range of 0.05-100 MUg/L with
detection limits in the range of 0.006-0.05 MUg/L. The relative standard
deviations were 0.33-3.64% (n = 6). The proposed method was applied to different
water samples collected from a drinking water plant to determine the
concentrations of haloacetic acids.
PMID- 27484360
TI - Novel complex mutation in NPM1 gene in patient with acute myeloid leukemia.
PMID- 27484361
TI - Multivariate analysis of ultrasound-recorded dorsal strain sequences:
Investigation of dynamic neck extensions in women with chronic whiplash
associated disorders.
AB - Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden
that is common after a whiplash injury. Tools to assist in the diagnosis of WAD
and an increased understanding of neck muscle behaviour are needed. We examined
the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus
healthy controls during the entire sequence of a dynamic low-loaded neck
extension exercise, which was recorded using real-time ultrasound movies with
high frame rates. Principal component analysis and orthogonal partial least
squares were used to analyse mechanical muscle strain (deformation in elongation
and shortening). The WAD group showed more shortening during the neck extension
phase in the trapezius muscle and during both the neck extension and the return
to neutral phase in the multifidus muscle. For the first time, a novel non
invasive method is presented that is capable of detecting altered dorsal muscle
strain in women with WAD during an entire exercise sequence. This method may be a
breakthrough for the future diagnosis and treatment of WAD.
PMID- 27484362
TI - Drosophila melanogaster females restore their attractiveness after mating by
removing male anti-aphrodisiac pheromones.
AB - Males from many species ensure paternity by preventing their mates from
copulating with other males. One mate-guarding strategy involves marking females
with anti-aphrodisiac pheromones (AAPs), which reduces the females'
attractiveness and dissuades other males from courting. Since females benefit
from polyandry, sexual conflict theory predicts that females should develop
mechanisms to counteract AAPs to achieve additional copulations, but no such
mechanisms have been documented. Here we show that during copulation Drosophila
melanogaster males transfer two AAPs: cis-Vaccenyl Acetate (cVA) to the females'
reproductive tract, and 7-Tricosene (7-T) to the females' cuticle. A few hours
after copulation, females actively eject cVA from their reproductive tract, which
results in increased attractiveness and re-mating. Although 7-T remains on those
females, we show that it is the combination of the two chemicals that reduces
attractiveness. To our knowledge, female AAP ejection provides the first example
of a female mechanism that counter-acts chemical mate-guarding.
PMID- 27484363
TI - Testicular toxicity following separate and combined administration of PDE5
inhibitors and opioid: assessment of recovery following their withdrawal.
AB - We previously observed that PDE5 inhibitors and opioids were widely abused in
Nigeria. Here, we examined the effect of high doses of sildenafil, tadalafil,
tramadol and sildenafil + tramadol on reproductive toxicity in male rats. Rats
were either administered normal saline (0.2 ml), sildenafil (10 mg/kg), tadalafil
(10 mg/kg), tramadol (20 mg/kg) or sildenafil + tramadol (10 and 20 mg/kg
respectively) p. o. for 8 weeks. The recovery groups were allowed 8-week recovery
period before sacrifice. Results showed that body weight change, testicular and
epididymal weights, epididymal sperm count and sperm viability were significantly
reduced in all treated groups compared with the control. Spermatozoa with
abnormal morphology were significantly increased in all treated groups compared
with the control. Superoxide dismutase (SOD), catalase (CAT), glutathione
peroxidase (GPx) and glutathione (GSH) were significantly reduced, while
malondialdehyde (MDA) was significantly increased in all treated groups compared
with the control. The severity of toxicity was highest in sildenafil + tramadol
group. There was no complete recovery from reproductive toxicity following
withdrawal of the various treatments. High doses of sildenafil, tadalafil,
tramadol or sildenafil + tramadol result in testicular oxidative stress-induced
reproductive toxicity with poor reversal following withdrawal.
PMID- 27484364
TI - Symbiotic gut commensal bacteria act as host cathepsin S activity regulators.
AB - Cathepsin S (CTSS) is a lysosomal protease whose activity regulation is important
for MHC-II signaling and subsequent activation of CD4+ T cell mediated immune
responses. Dysregulation of its enzymatic activity or enhanced secretion into
extracellular environments is associated with the induction or progression of
several autoimmune diseases. Here we demonstrate that commensal intestinal
bacteria influence secretion rates and intracellular activity of host CTSS and
that symbiotic bacteria, i.e. Bacteroides vulgatus mpk, may actively regulate
this process and help to maintain physiological levels of CTSS activities in
order to prevent from induction of pathological inflammation. The symbiont
controlled regulation of CTSS activity is mediated by anticipating reactive
oxygen species induction in dendritic cells which, in turn, maintains cystatin C
(CysC) monomer binding to CTSS. CysC monomers are potent endogenous CTSS
inhibitors. This Bacteroides vulgatus caused and CysC dependent CTSS activity
regulation is involved in the generation of tolerant intestinal dendritic cells
contributing to prevention of T-cell mediated induction of colonic inflammation.
Taken together, we demonstrate that symbionts of the intestinal microbiota
regulate host CTSS activity and secretion and might therefore be an attractive
approach to deal with CTSS associated autoimmune diseases.
PMID- 27484365
TI - Strategies for Improving Patient Comfort During Intravitreal Injections: Results
from a Survey-Based Study.
AB - INTRODUCTION: Many ocular diseases require intravitreal injections of
pharmacological agents. Optimizing patients' experiences during injections is
important to ensure compliance and maintenance of quality of life. The objective
of this study was to identify strategies to help alleviate discomfort during
intravitreal injections. METHODS: A cross-sectional study surveying 128 patients
during clinic visits between 2014 and 2015 in two outpatient Retina Clinics (one
academic and one private). Patients receiving an intravitreal injection(s) for
any retinal disorder were given a questionnaire with 10-yes/no responses for
various potential strategies. Responses were stratified by sex, age (<30 years,
30-60 years, and >60 years) and total number of prior injections (0-9 injections,
10-20 injections and >20 injections). RESULTS: A total of 128 patients were
surveyed: 59 males, 41 females and 28 with no sex specified. Our results
identified four favorable strategies as those receiving more than 50% "yes"
votes. These included the presence of technician/staff during the procedure, the
use of a neck pillow, a verbal warning before the injection and performing
injections in both eyes on the same day. Other specific strategies were
identified for females, younger patients and those with greatest experience.
These included: females preferred having their hand held during injections (P =
0.001) and using a stress ball (P = 0.000) when compared to males. Stratifying by
age, patients 30-60 years old preferred having their hand held (P = 0.008) and
background music (P = 0.007). Stratifying by prior injections, patients with >20
prior injections preferred having their hand held (P = 0.001), using a stress
ball (P = 0.021) and, if necessary, having bilateral injections performed the
same day to improve comfort (P = 0.037). CONCLUSIONS: Having an extra staff
member present during the injection, having a neck pillow, having a verbal
warning prior to injection and having both eyes injected on the same day were
indicated as favorable strategies by over half of those surveyed. Further,
specific strategies were identified for females, younger patients (30-60 years
old) and those with greatest experience (>20 injections).
PMID- 27484366
TI - Introduction to the special issue on crystal structure prediction.
PMID- 27484367
TI - Crystal structure prediction: are we there yet?
AB - This contribution comments on the advances of the latest Crystal Structure
Prediction blind test and the challenges still lying ahead.
PMID- 27484369
TI - Transferable force field for crystal structure predictions, investigation of
performance and exploration of different rescoring strategies using DFT-D
methods.
AB - A new force field, here called AZ-FF, aimed at being used for crystal structure
predictions, has been developed. The force field is transferable to a new type of
chemistry without additional training or modifications. This makes the force
field very useful in the prediction of crystal structures of new drug molecules
since the time-consuming step of developing a new force field for each new
molecule is circumvented. The accuracy of the force field was tested on a set of
40 drug-like molecules and found to be very good where observed crystal
structures are found at the top of the ranked list of tentative crystal
structures. Re-ranking with dispersion-corrected density functional theory (DFT
D) methods further improves the scoring. After DFT-D geometry optimization the
observed crystal structure is found at the leading top of the ranking list. DFT-D
methods and force field methods have been evaluated for use in predicting
properties such as phase transitions upon heating, mechanical properties or
intrinsic crystalline solubility. The utility of using crystal structure
predictions and the associated material properties in risk assessment in
connection with form selection in the drug development process is discussed.
PMID- 27484370
TI - An optimized intermolecular force field for hydrogen-bonded organic molecular
crystals using atomic multipole electrostatics.
AB - We present a re-parameterization of a popular intermolecular force field for
describing intermolecular interactions in the organic solid state. Specifically
we optimize the performance of the exp-6 force field when used in conjunction
with atomic multipole electrostatics. We also parameterize force fields that are
optimized for use with multipoles derived from polarized molecular electron
densities, to account for induction effects in molecular crystals.
Parameterization is performed against a set of 186 experimentally determined, low
temperature crystal structures and 53 measured sublimation enthalpies of hydrogen
bonding organic molecules. The resulting force fields are tested on a validation
set of 129 crystal structures and show improved reproduction of the structures
and lattice energies of a range of organic molecular crystals compared with the
original force field with atomic partial charge electrostatics. Unit-cell
dimensions of the validation set are typically reproduced to within 3% with the
re-parameterized force fields. Lattice energies, which were all included during
parameterization, are systematically underestimated when compared with measured
sublimation enthalpies, with mean absolute errors of between 7.4 and 9.0%.
PMID- 27484371
TI - Crystal structure prediction of rigid molecules.
AB - A non-polarizable force field based on atomic multipoles fit to reproduce
experimental crystal properties and ab initio gas-phase dimers is described. The
Ewald method is used to calculate both long-range electrostatic and 1/r(6)
dispersion energies of crystals. The dispersion energy of a crystal calculated by
a cutoff method is shown to converge slowly to the exact Ewald result. A method
for constraining space-group symmetry during unit-cell optimization is derived.
Results for locally optimizing 4427 unit cells including volume, cell parameters,
unit-cell r.m.s.d. and CPU timings are given for both flexible and rigid molecule
optimization. An algorithm for randomly generating rigid molecule crystals is
described. Using the correct experimentally determined space group, the average
and maximum number of random crystals needed to find the correct experimental
structure is given for 2440 rigid single component crystals. The force field
energy rank of the correct experimental structure is presented for the same set
of 2440 rigid single component crystals assuming the correct space group. A
complete crystal prediction is performed for two rigid molecules by searching
over the 32 most probable space groups.
PMID- 27484372
TI - Organic crystal polymorphism: a benchmark for dispersion-corrected mean-field
electronic structure methods.
AB - We analyze the energy landscape of the sixth crystal structure prediction blind
test targets with various first principles and semi-empirical quantum chemical
methodologies. A new benchmark set of 59 crystal structures (termed POLY59) for
testing quantum chemical methods based on the blind test target crystals is
presented. We focus on different means to include London dispersion interactions
within the density functional theory (DFT) framework. We show the impact of
pairwise dispersion corrections like the semi-empirical D2 scheme, the Tkatchenko
Scheffler (TS) method, and the density-dependent dispersion correction dDsC.
Recent methodological progress includes higher-order contributions in both the
many-body and multipole expansions. We use the D3 correction with Axilrod-Teller
Muto type three-body contribution, the TS based many-body dispersion (MBD), and
the nonlocal van der Waals density functional (vdW-DF2). The density functionals
with D3 and MBD correction provide an energy ranking of the blind test polymorphs
in excellent agreement with the experimentally found structures. As a
computationally less demanding method, we test our recently presented minimal
basis Hartree-Fock method (HF-3c) and a density functional tight-binding
Hamiltonian (DFTB). Considering the speed-up of three to four orders of
magnitudes, the energy ranking provided by the low-cost methods is very
reasonable. We compare the computed geometries with the corresponding X-ray data
where TPSS-D3 performs best. The importance of zero-point vibrational energy and
thermal effects on crystal densities is highlighted.
PMID- 27484368
TI - Report on the sixth blind test of organic crystal structure prediction methods.
AB - The sixth blind test of organic crystal structure prediction (CSP) methods has
been held, with five target systems: a small nearly rigid molecule, a polymorphic
former drug candidate, a chloride salt hydrate, a co-crystal and a bulky flexible
molecule. This blind test has seen substantial growth in the number of
participants, with the broad range of prediction methods giving a unique insight
into the state of the art in the field. Significant progress has been seen in
treating flexible molecules, usage of hierarchical approaches to ranking
structures, the application of density-functional approximations, and the
establishment of new workflows and 'best practices' for performing CSP
calculations. All of the targets, apart from a single potentially disordered Z' =
2 polymorph of the drug candidate, were predicted by at least one submission.
Despite many remaining challenges, it is clear that CSP methods are becoming more
applicable to a wider range of real systems, including salts, hydrates and larger
flexible molecules. The results also highlight the potential for CSP calculations
to complement and augment experimental studies of organic solid forms.
PMID- 27484373
TI - How important is thermal expansion for predicting molecular crystal structures
and thermochemistry at finite temperatures?
AB - Molecular crystals expand appreciably upon heating due to both zero-point and
thermal vibrational motion, yet this expansion is often neglected in molecular
crystal modeling studies. Here, a quasi-harmonic approximation is coupled with
fragment-based hybrid many-body interaction calculations to predict thermal
expansion and finite-temperature thermochemical properties in crystalline carbon
dioxide, ice Ih, acetic acid and imidazole. Fragment-based second-order Moller
Plesset perturbation theory (MP2) and coupled cluster theory with singles,
doubles and perturbative triples [CCSD(T)] predict the thermal expansion and the
temperature dependence of the enthalpies, entropies and Gibbs free energies of
sublimation in good agreement with experiment. The errors introduced by
neglecting thermal expansion in the enthalpy and entropy cancel somewhat in the
Gibbs free energy. The resulting ~ 1-2 kJ mol(-1) errors in the free energy near
room temperature are comparable to or smaller than the errors expected from the
electronic structure treatment, but they may be sufficiently large to affect free
energy rankings among energetically close polymorphs.
PMID- 27484374
TI - Generation of crystal structures using known crystal structures as analogues.
AB - This analysis attempts to answer the question of whether similar molecules
crystallize in a similar manner. An analysis of structures in the Cambridge
Structural Database shows that the answer is yes - sometimes they do,
particularly for single-component structures. However, one does need to define
what we mean by similar in both cases. Building on this observation we then
demonstrate how this correlation between shape similarity and packing similarity
can be used to generate potential lattices for molecules with no known crystal
structure. Simple intermolecular interaction potentials can be used to minimize
these potential lattices. Finally we discuss the many limitations of this
approach.
PMID- 27484375
TI - Exploring polymorphism of benzene and naphthalene with free energy based enhanced
molecular dynamics.
AB - Prediction and exploration of possible polymorphism in organic crystal compounds
are of great importance for industries ranging from organic electronics to
pharmaceuticals to high-energy materials. Here we apply our crystal structure
prediction procedure and the enhanced molecular dynamics based sampling approach
called the Crystal-Adiabatic Free Energy Dynamics (Crystal-AFED) method to
benzene and naphthalene. Crystal-AFED allows the free energy landscape of
structures to be explored efficiently at any desired temperature and pressure.
For each system, we successfully predict the most stable crystal structures at
atmospheric pressure and explore the relative Gibbs free energies of predicted
polymorphs at high pressures. Using Crystal-AFED sampling, we find that mixed
structures, which typically cannot be discovered by standard crystal structure
prediction methods, are prevalent in the solid forms of these compounds at high
pressure.
PMID- 27484377
TI - Effect of packing motifs on the energy ranking and electronic properties of
putative crystal structures of tricyano-1,4-dithiino[c]-isothiazole.
AB - We present an analysis of putative structures of tricyano-1,4-dithiino[c]
isothiazole (TCS3), generated within the sixth crystal structure prediction blind
test. Typical packing motifs are identified and characterized in terms of
distinct patterns of close contacts and regions of electrostatic and dispersion
interactions. We find that different dispersion-inclusive density functional
theory (DFT) methods systematically favor specific packing motifs, which may
affect the outcome of crystal structure prediction efforts. The effect of crystal
packing on the electronic and optical properties of TCS3 is investigated using
many-body perturbation theory within the GW approximation and the Bethe-Salpeter
equation (BSE). We find that a structure with Pna21 symmetry and a bilayer
packing motif exhibits intermolecular bonding patterns reminiscent of pi-pi
stacking and has markedly different electronic and optical properties than the
experimentally observed P21/n structure with a cyclic dimer motif, including a
narrower band gap, enhanced band dispersion and broader optical absorption. The
Pna21 bilayer structure is close in energy to the observed structure and may be
feasible to grow.
PMID- 27484376
TI - Using crystal structure prediction to rationalize the hydration propensities of
substituted adamantane hydrochloride salts.
AB - The crystal energy landscapes of the salts of two rigid pharmaceutically active
molecules reveal that the experimental structure of amantadine hydrochloride is
the most stable structure with the majority of low-energy structures adopting a
chain hydrogen-bond motif and packings that do not have solvent accessible voids.
By contrast, memantine hydrochloride which differs in the substitution of two
methyl groups on the adamantane ring has a crystal energy landscape where all
structures within 10 kJ mol(-1) of the global minimum have solvent-accessible
voids ranging from 3 to 14% of the unit-cell volume including the lattice energy
minimum that was calculated after removing water from the hydrated memantine
hydrochloride salt structure. The success in using crystal structure prediction
(CSP) to rationalize the different hydration propensities of these substituted
adamantane hydrochloride salts allowed us to extend the model to predict under
blind test conditions the experimental crystal structures of the previously
uncharacterized 1-(methylamino)adamantane base and its corresponding
hydrochloride salt. Although the crystal structure of 1-(methylamino)adamantane
was correctly predicted as the second ranked structure on the static lattice
energy landscape, the crystallization of a Z' = 3 structure of 1
(methylamino)adamantane hydrochloride reveals the limits of applying CSP when the
contents of the crystallographic asymmetric unit are unknown.
PMID- 27484378
TI - An insight into real and average structure from diffuse X-ray scattering - a case
study.
AB - Two-dimensional diffuse X-ray scattering from an organic salt [N-(3-(2,6
dimethylanilino)-1-methylbut-2-enylidene)-2,6-dimethylanilinium chloride,
C21H27N2(+)Cl(-)] was interpreted with the help of an analytical model of diffuse
scattering. An analysis of the relationship between symmetry and diffuse
scattering for the studied system has been undertaken. The symmetry of the system
explains the extinction pattern, taking the form of curves, on the diffuse
scattering planes. We have also tested the relationship between the average
structure model and scattering intensities. Two models, differing in their
representation of overlapping atoms, were used. In the case of diffuse scattering
the difference between resulting intensities is immense, while for the Bragg
intensities it is much smaller. This sensitivity of diffuse scattering could
potentially be used to improve the description of the average structure.
PMID- 27484379
TI - Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing
of related triterpene molecules.
AB - The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are
reported. X-ray crystallography revealed that despite differences in the size of
the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of
molecular self-assembly is similar in all three cases but differs significantly
from that observed in other known GE esters. According to our analysis, the two
basic patterns of self-assembly of GE esters observed in their unsolvated
crystals correspond to two distinct orientations of the ester groups relative to
the triterpene backbone. Moreover, comparison of the self-assembly modes of GE
esters in their unsolvated forms with the supramolecular organization of GE and
carbenoxolone in their solvated crystals revealed that ester substituents replace
solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton,
resulting in similar packing arrangements of these compounds.
PMID- 27484380
TI - Growth, morphology, structure and characterization of L-histidinium dihydrogen
arsenate orthoarsenic acid single crystal.
AB - L-Histidinium dihydrogen arsenate orthoarsenic acid (LHAS) crystals were grown by
the slow evaporation method. Single-crystal X-ray diffraction confirms monoclinic
structure. The growth rates of various planes of LHAS crystals were estimated by
morphological study. Hirshfeld surface and fingerprint plots were analyzed to
investigate the intermolecular interactions at 0.002 a.u. present in the crystal
structure. The functional groups and phase behavior of the compound are studied
by FTIR spectroscopy and differential scanning calorimetry (DSC). A ferroelectric
to paraelectric phase transition at 307 K was observed in dielectric studies. The
piezoelectric charge coefficients of the grown crystal were found to be 2 pC/N.
The values of coercive field (Ec), remnant polarization (Pr) and spontaneous
polarization (Ps) in the hysteresis loop are found to be 5.236 kV cm(-1), 0.654
uC cm(-2) and 2.841 uC cm(-2), respectively. Piezoelectricity and
ferroelectricity are reported for the first time in LHAS crystals. The mechanical
strength was confirmed from microhardness study and void volume. Due to the low
value of the dielectric constant, and good piezoelectric and ferroelectric
properties, LHAS crystals can be used in microelectronics, sensors and advanced
electronic devices.
PMID- 27484381
TI - Bond-length distributions for ions bonded to oxygen: alkali and alkaline-earth
metals.
AB - Bond-length distributions have been examined for 55 configurations of alkali
metal ions and 29 configurations of alkaline-earth-metal ions bonded to oxygen,
for 4859 coordination polyhedra and 38 594 bond distances (alkali metals), and
for 3038 coordination polyhedra and 24 487 bond distances (alkaline-earth
metals). Bond lengths generally show a positively skewed Gaussian distribution
that originates from the variation in Born repulsion and Coulomb attraction as a
function of interatomic distance. The skewness and kurtosis of these
distributions generally decrease with increasing coordination number of the
central cation, a result of decreasing Born repulsion with increasing
coordination number. We confirm the following minimum coordination numbers:
([3])Li(+), ([3])Na(+), ([4])K(+), ([4])Rb(+), ([6])Cs(+), ([3])Be(2+),
([4])Mg(2+), ([6])Ca(2+), ([6])Sr(2+) and ([6])Ba(2+), but note that some
reported examples are the result of extensive dynamic and/or positional short
range disorder and are not ordered arrangements. Some distributions of bond
lengths are distinctly multi-modal. This is commonly due to the occurrence of
large numbers of structure refinements of a particular structure type in which a
particular cation is always present, leading to an over-representation of a
specific range of bond lengths. Outliers in the distributions of mean bond
lengths are often associated with anomalous values of atomic displacement of the
constituent cations and/or anions. For a sample of ([6])Na(+), the ratio
Ueq(Na)/Ueq(bonded anions) is partially correlated with <([6])Na(+)-O(2-)> (R(2)
= 0.57), suggesting that the mean bond length is correlated with
vibrational/displacement characteristics of the constituent ions for a fixed
coordination number. Mean bond lengths also show a weak correlation with bond
length distortion from the mean value in general, although some coordination
numbers show the widest variation in mean bond length for zero distortion, e.g.
Li(+) in [4]- and [6]-coordination, Na(+) in [4]- and [6]-coordination. For
alkali-metal and alkaline-earth-metal ions, there is a positive correlation
between cation coordination number and the grand mean incident bond-valence sum
at the central cation, the values varying from 0.84 v.u. for ([5])K(+) to 1.06
v.u. for ([8])Li(+), and from 1.76 v.u. for ([7])Ba(2+) to 2.10 v.u. for
([12])Sr(2+). Bond-valence arguments suggest coordination numbers higher than
[12] for K(+), Rb(+), Cs(+) and Ba(2+).
PMID- 27484382
TI - On the effective ionic radii for ammonium.
AB - A set of effective ionic radii corresponding to different coordination numbers
(CNs) and compatible with the radii system by Shannon [Acta Cryst. (1976), A32,
751-767] has been derived for ammonium: 1.40 A (CN = IV), 1.48 A (CN = VI), 1.54
A (CN = VIII) and 1.67 A (CN = XII). The bond-valence parameters r0 = 2.3433 A
and B = 0.262 A have been determined for ammonium-fluorine bonds.
PMID- 27484383
TI - Structure and topology of three-dimensional hydrocarbon polymers.
AB - A new family of three-dimensional hydrocarbon polymers which are more
energetically favorable than benzene is proposed. Although structurally these
polymers are closely related to well known diamond and lonsdaleite carbon
structures, using topological arguments we demonstrate that they have no known
structural analogs. Topological considerations also give some indication of
possible methods of synthesis. Taking into account their exceptional optical,
structural and mechanical properties these polymers might have interesting
applications.
PMID- 27484384
TI - Modulated crystal structure of InMo4O6.
AB - The (3 + 1)-dimensional modulated crystal structure of the metal-rich cluster
compound InMo4O6 was solved and refined from single-crystal data in the
superspace group P4/mbm(00gamma)00ss [q = 0, 0, 0.1536 (4); a = 9.6664 (9), c =
2.8645 (3) A; R1(all) = 0.046, wR(all) = 0.076]. The crystal structure is closely
related to the NaMo4O6 structure type. It is built from rods of Mo6 clusters
condensed via trans edges. These form channels parallel to [001], in which In6
and In7 oligomers alternate. Weak diffuse planes parallel to (001)* interconnect
the satellite reflections; they occur due to two-dimensional rod disorder of the
In oligomer chains.
PMID- 27484385
TI - Structures of N-acetyl-DL-isoleucine, N-acetyl-DL-alloisoleucine and their
ammonium salts; role of ammonium ions in crystal structure formation.
AB - The crystal structures of N-acetyl-DL-isoleucine, N-acetyl-DL-alloisoleucine and
their ammonium salts show that these four compounds exist as racemic compounds
around room temperature. The two ammonium salts are arranged around a 21 screw
axis, forming a helical column which consists of ammonium ions and single
enantiomeric anions similar to the crystals of the ammonium salts of optically
active N-acetyl-L-isoleucine and N-acetyl-D-alloisoleucine. The ammonium ion and
the carboxylate ion in the helix are connected by three hydrogen bonds, the
fourth hydrogen bond being formed between the ammonium ion and an external acetyl
amino group of the neighboring helical column. The fourth hydrogen bond is formed
between the ammonium ion and an external acetyl amino group of the neighboring 21
column. Ammonium N-acetyl-DL-alloisoleucinate was revealed to exist as an
unstable racemic compound due to conformational similarity between the racemic
and optically active compounds in the solid state and was optically resolved by
fractional crystallization at 293 K.
PMID- 27484386
TI - Magnetic Resonance Imaging Underestimation of Prostate Cancer Geometry: Use of
Patient Specific Molds to Correlate Images with Whole Mount Pathology.
AB - PURPOSE: We evaluated the accuracy of magnetic resonance imaging in determining
the size and shape of localized prostate cancer. MATERIALS AND METHODS: The
subjects were 114 men who underwent multiparametric magnetic resonance imaging
before radical prostatectomy with patient specific mold processing of the
specimen from 2013 to 2015. T2-weighted images were used to contour the prostate
capsule and cancer suspicious regions of interest. The contours were used to
design and print 3-dimensional custom molds, which permitted alignment of excised
prostates with magnetic resonance imaging scans. Tumors were reconstructed in 3
dimensions from digitized whole mount sections. Tumors were then matched with
regions of interest and the relative geometries were compared. RESULTS: Of the
222 tumors evident on whole mount sections 118 had been identified on magnetic
resonance imaging. For the 118 regions of interest mean volume was 0.8 cc and the
longest 3-dimensional diameter was 17 mm. However, for matched pathological
tumors, of which most were Gleason score 3 + 4 or greater, mean volume was 2.5 cc
and the longest 3-dimensional diameter was 28 mm. The median tumor had a 13.5 mm
maximal extent beyond the magnetic resonance imaging contour and 80% of cancer
volume from matched tumors was outside region of interest boundaries. Size
estimation was most accurate in the axial plane and least accurate along the base
apex axis. CONCLUSIONS: Magnetic resonance imaging consistently underestimates
the size and extent of prostate tumors. Prostate cancer foci had an average
diameter 11 mm longer and a volume 3 times greater than T2-weighted magnetic
resonance imaging segmentations. These results may have important implications
for the assessment and treatment of prostate cancer.
PMID- 27484389
TI - Experimental design-based optimization of lipid nanocarrier as delivery system
against Mycobacterium species: in vitro and in vivo evaluation.
AB - The study aimed to optimize self-nanoemulsifying drug delivery system using
experimental design using excipients holding innate anti-mycobacterium activities
followed with characterizations for responses such as optical clarity (Y1), zone
of inhibition (ZOI) against Mycobacterium smegmatis strains (Y2, Y3), and
globular size (Y4). The optimized formulations (OF1-OF3) were further
characterized for responses and evaluated for zeta potential, minimum inhibition
concentration (MIC) against non-pathogenic and tubercular strains, morphological
(electron microscopy and atomic force microscopy), and confocal laser scanning
microscopy (CLSM) studies. The desirability analysis suggested that the predicted
values of the OF1 for the responses Y1, Y2, Y3, and Y4 were 0.137, 22.77 mm, 21.9
mm, and 191.11 nm, respectively. The morphological assessment confirmed the in
vitro studies and established the inhibition mechanism as evidenced with oozing,
ablation, and cell-wall fragmentation followed with cell disruption. The OF1,
OF2, and OF3 showed an MIC value at 8.8 +/- 0.56 mg/ml, 12.5 +/- 0.22 mg/ml, and
15.0 +/- 0.4 mg/ml, respectively, corroborating effectiveness against tubercular
strain. CLSM studies revealed 75.1, 80.3, and 88.7% as an intense fluorescence
intensity of OF1, OF2, and OF3, respectively, as compared with dye solution
(~53%). Conclusively, it can be inferred that the delivery of anti-tubercular
drugs might be reassessed using excipients with inherent anti-mycobacterium
activities.
PMID- 27484391
TI - Sub-Saharan African migrant youths' help-seeking barriers and facilitators for
mental health and substance use problems: a qualitative study.
AB - BACKGROUND: Many young migrants and their parents are reluctant to seek help for
mental health and substance use problems. Help-seeking delays can result in
longer duration of untreated problems and poorer outcomes. In this study, we
aimed to identify the help-seeking barriers and facilitators for anxiety,
depression and alcohol and drug use problems in young people from recently
established sub-Saharan African migrant communities. METHODS: A qualitative
study, incorporating individual, in-depth interviews and focus group discussions,
was undertaken in Melbourne, Australia. Twenty-eight young sub-Saharan African
migrants participated in the individual interviews, and 41 sub-Saharan African
born parents and key community leaders participated in 4 focus groups. All
participants were aged 16 years or over. A thematic analysis of the data was
undertaken. RESULTS: Themes and related sub-themes were abstracted from the data,
reflecting the young people's, parents' and key community leaders' beliefs about
barriers and facilitators to help-seeking for mental health and substance use
problems. Four help-seeking barriers were identified: stigma of mental illness,
lack of mental health literacy in parents and young people, lack of cultural
competency of formal help sources, and financial costs deterring access. Five
help-seeking facilitators were abstracted: being open with friends and family,
strong community support systems, trustworthiness and confidentiality of help
sources, perceived expertise of formal help-sources, increasing young people's
and parents' mental health literacy. CONCLUSION: Programs that identify and build
on help-seeking facilitators while addressing help-seeking barriers are needed to
address mental health issues among young sub-Saharan African migrants. Strategies
to address help-seeking barriers should consider counteracting stigma and
increasing mental health literacy in sub-Saharan African communities, increasing
health providers' cultural competency and perceived trustworthiness, and
addressing financial barriers to accessing services.
PMID- 27484392
TI - Mostly Smokers: Identifying Subtypes of Emerging Adult Substance Users.
AB - BACKGROUND: The concurrent use of marijuana and other substances among emerging
adults (ages 18-25) is a major public health problem. This study examined if
there are distinct subtypes of emerging adult marijuana users and if these are
associated with demographic and substance use variables. METHODS: The design was
a cross-sectional interview with a community sample of 1,503 emerging adults in
the northeastern U.S. who reported last month marijuana use. We used latent class
analysis (LCA) to identify distinct subtypes of emerging adults who used
additional substances and examined predictors of the latent classes. RESULTS: We
identified three distinct classes of emerging adults who use substances: "mostly
smokers" (those who primarily use marijuana and nicotine), "moderate users"
(those who primarily use marijuana and/or heavy episodic alcohol), and
"polysubstance users." Polysubstance users had higher probabilities of use of all
assessed substances (e.g. cocaine, opiates, sleep medications, stimulants,
synthetic marijuana, and inhalants) than the other two groups. Not being
currently enrolled in school and male gender were associated with mostly smokers
and polysubstance users group status. CONCLUSIONS: We identified a distinct group
of emerging adult marijuana users who primarily smoke marijuana and cigarettes,
suggesting that there could be a shared vulnerability for risk of co-occurrence.
PMID- 27484393
TI - Homochiral [2.2]Paracyclophane Self-Assembly Promoted by Transannular Hydrogen
Bonding.
AB - [2.2]paracyclophane (pCp), unlike many pi-building blocks, has been virtually
unexplored in supramolecular constructs. Reported here is the synthesis and
characterization of the first pCp derivatives capable of programmed self-assembly
into extended cofacial pi-stacks in solution and the solid state. The design
employs transannular (intramolecular) hydrogen bonds (H-bonds), hitherto
unstudied in pCps, between pseudo-ortho-positioned amides of a pCp-4,7,12,15
tetracarboxamide (pCpTA) to preorganize the molecules for intermolecular H
bonding with pi-stacked neighbors. X-ray crystallography confirms the formation
of homochiral, one-dimensional pCpTA stacks helically laced with two H-bond
strands. The chiral sense is dictated by the planar chirality (Rp or Sp ) of the
pCpTA monomers. A combination of NMR, IR, and UV/Vis studies confirms the
formation of the first supramolecular pCp polymers in solution.
PMID- 27484394
TI - Sexual objectification in women's daily lives: A smartphone ecological momentary
assessment study.
AB - Sexual objectification, particularly of young women, is highly prevalent in
modern industrialized societies. Although there is plenty of experimental and
cross-sectional research on objectification, prospective studies investigating
the prevalence and psychological impact of objectifying events in daily life are
scarce. We used ecological momentary assessment to track the occurrence of
objectifying events over 1 week in the daily lives of young women (N = 81).
Participants reported being targeted by a sexually objectifying event - most
often the objectifying gaze - approximately once every 2 days and reported
witnessing sexual objectification of others approximately 1.35 times per day.
Further, multilevel linear regression analyses showed that being targeted by
sexual objectification was associated with a substantial increase in state self
objectification. Overall, individual differences had little impact in moderating
these effects.
PMID- 27484395
TI - Effects of Funnelliformis mosseae inoculation on alleviating atrazine damage in
Canna indica L. var. flava Roxb.
AB - Atrazine residue in the environment continually damages plants and therefore
requires immediate attention and effective development of methods for its
decontamination. The effects of Funnelliformis mosseae inoculation on growth and
physiology in atrazine-treated Canna indica L. var. flava Roxb. were
investigated. At atrazine concentrations up to 15 mg L-1, the growth of C. indica
plants were negatively affected. Inoculation with F. mosseae alleviated the
atrazine inhibition of plant growth and biomass. Furthermore, the chlorophyll
content and root function increased under F. mosseae inoculation, and the
oxidative stress of malondialdehyde, peroxidase, and superoxide dismutase
activities induced by atrazine were also alleviated by F. mosseae inoculation.
The removal rate of atrazine by untreated C. indica was significant, with removal
rates of 20.5-55.3% by the end of a 14-day experiment; however, F. mosseae
inoculation increased the removal rate to 35.6-75.1%. In conclusion, F. mosseae
inoculation can alleviate the damage induced by atrazine in C. indica.
Accordingly, C. indica inoculated with F. mosseae has excellent potential to be
used in phytoremediation in habitats polluted by high atrazine concentrations.
PMID- 27484396
TI - Polarized dosimetry method for Gafchromic EBT3.
AB - PURPOSE: To analyze the changes in the polarization state of the flatbed scanner
light caused by the EBT3 films and to propose a new method for correcting the
lateral effects. METHODS AND MATERIALS: The polarization changes induced by
radiochromic films are analyzed using linear polarizing film. Based on the
results, the linear polarizing films are used in the scanning process of the EBT3
films. This method is tested against the conventional EBT3 dosimetry using a
series of simple regular beams and 21 cases of IMRT. RESULTS: The mean results
are statically different from the conventional dosimetry with EBT3. Depending on
the transmission axis of the polarizing sheet, the results are better or worse
compared to conventional dosimetry EBT3 film. When the transmission axis of the
polarizing sheet is parallel to the coating direction, the dosimetry results are
better and its variability is smaller. However, when the polarizer transmission
axis is perpendicular to the coating direction, results are worse as well as its
variability. CONCLUSION: Using a polarized film with the polarization axis
parallel to the coating direction of the radiochromic film, and preferably above
it, significantly improves the dosimetry results and is an easy and inexpensive
way to correct the lateral artifacts of the conventional EBT3 dosimetry.
PMID- 27484397
TI - Spectral optimization of iodine-enhanced CT: Quantifying the effect of tube
voltage on image quality and radiation exposure determined at an anthropomorphic
phantom.
AB - PURPOSE: To provide an experimental basis for spectral optimization of iodine
enhanced CT by a quantitative analysis of image quality and radiation dose
characteristics consistently measured for a large variety of scan settings at an
anthropomorphic phantom. METHODS: CT imaging and thermoluminescent dosimetry were
performed at an anthropomorphic whole-body phantom with iodine inserts for
different tube voltages (U, 70-140kV) and current-time products (Q, 60-300mAs).
For all U-Q combinations, the iodine contrast (C), the noise level (N) and, from
these, the contrast-to-noise ratio (CNR) of reconstructed CT images were
determined and parameterized as a function of U, Q or the measured absorbed dose
(D). Finally, two characteristic curves were derived that give the relative
increase of CNR at constant D and the relative decrease of D at constant CNR when
lowering U. RESULTS: Lowering U affects the measured CNR only slightly but
markedly reduces D. For example, reducing U from 120kV to 70kV increases the CNR
at constant D by a factor of nearly 1.8 or, alternatively, reduces D at constant
CNR by a factor of nearly 5. CONCLUSION: Spectral optimization by lowering U is
an effective approach to attain the necessary CNR for a specific diagnostic task
at hand while at the same time reducing radiation exposure as far as practically
achievable. The characteristic curves derived in this study from extensive
measurements at a reference 'person' can support CT users in an easy-to-use
manner to select an appropriate voltage for various clinical scenarios.
PMID- 27484398
TI - Early-Stage Capital Cost Estimation of Biorefinery Processes: A Comparative Study
of Heuristic Techniques.
AB - Biorefineries offer a promising alternative to fossil-based processing industries
and have undergone rapid development in recent years. Limited financial resources
and stringent company budgets necessitate quick capital estimation of pioneering
biorefinery projects at the early stages of their conception to screen process
alternatives, decide on project viability, and allocate resources to the most
promising cases. Biorefineries are capital-intensive projects that involve state
of-the-art technologies for which there is no prior experience or sufficient
historical data. This work reviews existing rapid cost estimation practices,
which can be used by researchers with no previous cost estimating experience. It
also comprises a comparative study of six cost methods on three well-documented
biorefinery processes to evaluate their accuracy and precision. The results
illustrate discrepancies among the methods because their extrapolation on
biorefinery data often violates inherent assumptions. This study recommends the
most appropriate rapid cost methods and urges the development of an improved
early-stage capital cost estimation tool suitable for biorefinery processes.
PMID- 27484399
TI - Risk factors for tuberculosis smear non-conversion in Eden district, Western
Cape, South Africa, 2007-2013: a retrospective cohort study.
AB - BACKGROUND: Tuberculosis (TB) continues to be a major global health problem.
While progress has been made to improve TB cure rates, South Africa's 76 % smear
positive pulmonary TB (PTB) case cure rate remains below the WHO target of 85 %.
We report on the trends of TB smear non-conversion and their predictors at the
end of an intensive phase of treatment, and how this impacted on treatment
outcomes of smear-positive PTB cases in Eden District, Western Cape Province,
South Africa. METHODS: Routinely collected, retrospective data of smear-positive
PTB cases from the electronic TB register in Eden District between 2007 and 2013
was extracted. Non-conversion was defined as persistent sputum smear-positive PTB
cases at the end of the two or three month intensive phase of treatment. Chi
square test for linear trend and simple linear regression analysis were used to
analyse the change in percentages and slope of TB smear non-conversion rates over
time. Risk factors for TB non-conversion, and their impact on treatment outcomes,
were evaluated using logistic regression models. RESULTS: Of 12,742 total smear
positive PTB cases included in our study, 12.8 % (n = 1627) did not sputum smear
convert; 13.3 % (1411 of 10,574) of new cases and 9.9 % (216 of 2168) of re
treatment cases. Although not statistically significant in either new or re
treatment cases, between 2007 and 2013, smear non-conversion decreased from 16.4
to 12.7 % (slope = -0.60; 95 % CI: -1.49 to 0.29; p = 0.142) in new cases, and
from 11.3 to 10.8 % in re-treatment cases (slope = -0.29; 95 % CI: -1.06 to 0.48;
p = 0.376). Male gender, HIV co-infection and a >2+ acid fast bacilli (AFB) smear
grading at the start of TB treatment were independent risk factors for non
conversion (p < 0.001). Age was a risk factor for non-conversion in new cases,
but not for re-treatment cases. Non-conversion was also associated with
unsuccessful treatment outcomes (p < 0.01), including treatment default and
treatment failure. CONCLUSIONS: Smear-positive PTB cases, especially men and
those with identified risk factors for non-conversion, should be closely
monitored throughout their treatment period. The South African TB control program
should invest in patient adherence counselling and education to mitigate TB non
conversion risk factors, and to improve conversion and TB cure rates.
PMID- 27484400
TI - Helicobacter pylori infection contributes to placental impairment in
preeclampsia: basic and clinical evidences.
AB - BACKGROUND: Preeclampsia (PE) is a major cause of maternal and neonatal morbidity
and mortality. Epidemiological association between Helicobacter pylori (Hp)
infection and PE onset has been widely shown. The aim of this study was to
analyze a possible correlation between Hp infection and the severity of clinical
presentation of PE and to identify an immunologic mechanism triggered by Hp
infection potentially contributing to the pathogenesis of PE. MATERIALS AND
METHODS: Sera from 93 preeclamptic women and 87 healthy pregnant women were
tested for Hp infection by immunoassay and for anti-CagA antibodies by Western
blot assay. The serologic results were correlated with the clinical features of
PE. The functional effect of serum IgG fractions, positive or negative for Hp,
from preeclamptic women or controls were tested on trophoblast and endothelial
cell cultures and in a murine model of angiogenesis. RESULTS: Preeclamptic women
showed higher seroprevalence of Hp infection (57.0%) compared to controls (33.3%)
(P<.001). The seropositivity for CagA-positive strains of Hp was 45.2% in
preeclamptic women vs 13.7% in controls (P<.001). In PE women, Hp infection was
associated with abnormality of uterine arteries Doppler (P<.001). Hp+ IgG
fractions from preeclamptic women bound to trophoblast and endometrial
endothelial cell cultures, reducing in vitro invasiveness and angiogenesis,
respectively, and inhibited angiogenesis in mice. CONCLUSIONS: Our data show, for
the first time, an association between Hp infection and PE with abnormal uterine
arteries Doppler velocimetry, suggesting a role for Hp infection in impairing
placental development and increasing the risk to develop PE. This study opens the
new perspective of a potential screening and treatment for Hp infection in
pregnancy.
PMID- 27484401
TI - High-brightness organic light-emitting diodes for optogenetic control of
Drosophila locomotor behaviour.
AB - Organic light emitting diodes (OLEDs) are in widespread use in today's mobile
phones and are likely to drive the next generation of large area displays and
solid-state lighting. Here we show steps towards their utility as a platform
technology for biophotonics, by demonstrating devices capable of optically
controlling behaviour in live animals. Using devices with a pin OLED
architecture, sufficient illumination intensity (0.3 mW.mm(-2)) to activate
channelrhodopsins (ChRs) in vivo was reliably achieved at low operating voltages
(5 V). In Drosophila melanogaster third instar larvae expressing ChR2(H134R) in
motor neurons, we found that pulsed illumination from blue and green OLEDs
triggered robust and reversible contractions in animals. This response was
temporally coupled to the timing of OLED illumination. With blue OLED
illumination, the initial rate and overall size of the behavioural response was
strongest. Green OLEDs achieved roughly 70% of the response observed with blue
OLEDs. Orange OLEDs did not produce contractions in larvae, in agreement with the
spectral response of ChR2(H134R). The device configuration presented here could
be modified to accommodate other small model organisms, cell cultures or tissue
slices and the ability of OLEDs to provide patterned illumination and spectral
tuning can further broaden their utility in optogenetics experiments.
PMID- 27484404
TI - Tissue engineering using pluripotent stem cells: multidisciplinary approaches to
accelerate bench-to-bedside transition.
PMID- 27484403
TI - Composite alginate gels for tunable cellular microenvironment mechanics.
AB - The mechanics of the cellular microenvironment can be as critical as biochemistry
in directing cell behavior. Many commonly utilized materials derived from extra
cellular-matrix create excellent scaffolds for cell growth, however, evaluating
the relative mechanical and biochemical effects independently in 3D environments
has been difficult in frequently used biopolymer matrices. Here we present 3D
sodium alginate hydrogel microenvironments over a physiological range of
stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen
fibers. We use confocal microscopy to measure the growth of multi-cellular
aggregates (MCAs), of increasing metastatic potential in different elastic moduli
of hydrogels, with and without binding factors. We find that the hydrogel
stiffness regulates the growth and morphology of these cell clusters; MCAs grow
larger and faster in the more rigid environments similar to cancerous breast
tissue (E = 4-12 kPa) as compared to healthy tissue (E = 0.4-2 kpa). Adding
binding factors from collagen and RGD peptides increases growth rates, and change
maximum MCA sizes. These findings demonstrate the utility of these independently
tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer
microenvironments may increase cell proliferation.
PMID- 27484402
TI - Association between bilirubin and risk of Non-Alcoholic Fatty Liver Disease based
on a prospective cohort study.
AB - The study aimed to assess the association between total, direct, and indirect
bilirubin and nonalcoholic fatty live disease (NAFLD) risk given its high
prevalence and serious clinical prognosis. Among 27,009 subjects who participated
in a healthy screening program from the Dongfeng-Tongji cohort study in 2008,
8189 eligible subjects (aged 35-86 years; males, 43.95%) were ultimately
enrolled. The incidence rates of NAFLD in 2013 were compared with respect to
baseline bilirubin levels among subjects free of NAFLD, and the effect sizes were
estimated by logistic regression analysis. During 5 years follow-up, we observed
1956 cases of newly developed NAFLD with the overall incidence of 23.88%. Direct
bilirubin was presented to inversely associate with NAFLD risk. Compared with
quartile 1 of direct bilirubin, the multivariable-adjusted ORs (95% CIs) for
NAFLD of quartile 2 to 4 were 1.104 (0.867-1.187), 0.843 (0.719-0.989), and 0.768
(0.652-0.905), respectively, P for trend 0.002). Similarly, inverse effects of
direct bilirubin on NAFLD incidence were also observed when stratified by sex and
BMI. However, no significant associations were found between total, and indirect
bilirubin and NAFLD risk. Direct bilirubin reduced NAFLD risk independent of
possible confounders among middle-aged and elderly Chinese population, probably
based on the endogenous antioxidation of bilirubin.
PMID- 27484405
TI - Semaphorin 3A-modified adipose-derived stem cell sheet may improve
osseointegration in a type 2 diabetes mellitus rat model.
AB - Although titanium (Ti) implants are considered to be an optimal choice for the
replacement of missing teeth, it remains difficult to obtain sufficient
osseointegration in patients with type 2 diabetes mellitus (T2DM). The present
study aimed to investigate whether adipose-derived stem cells (ASCs) may be used
to improve Ti implant osseointegration in T2DM conditions with the addition of
semaphorin 3A (Sema3A), a recently identified osteoprotective protein. Cell
morphology was observed using a scanning electron microscope. Cell proliferation
was determined using Cell Counting Kit-8. Osteogenic differentiation was
confirmed by the staining of alkaline phosphatase, collagen secretion and calcium
deposition. An in vivo evaluation was performed in the T2DM rat model, which was
induced by a high-fat diet and a low-dose streptozotocin intraperitoneal
injection. A Sema3A-modified ASC sheet was wrapped around the Ti implant, which
was subsequently inserted into the tibia. The rats were then exposed to Sema3A
stimulation. The morphology and proliferation ability of ASCs remained unchanged;
however, their osteogenic differentiation ability was increased. Micro-computed
tomography scanning and histological observations confirmed that formation of new
bone was improved with the use of the Sema3A-modified ASCs sheet. The present
study indicated that the Sema3A-modified ASCs sheet may be used to improve
osseointegration under T2DM conditions.
PMID- 27484407
TI - Bupropion improved apathy in behavioral variant frontotemporal dementia: a case
report.
AB - Apathy is a common neurobehavioral sign in cases of behavioral variant
frontotemporal dementia. However, there is still no established sustained
effective treatment. We present the case of a 65-year-old man with behavioral
variant frontotemporal dementia who suffered from severe apathy, but his apathy
improved after a 10-month period of bupropion treatment. His single photon
emission computed tomography report also showed slight improvement. To the best
of our knowledge, such a case with imaging evidence has never been reported.
Further studies to correlate the effects of bupropion on apathy in behavioral
variant frontotemporal dementia patients are clearly needed.
PMID- 27484408
TI - Effect of variety on content of bioactive phenolic compounds in common elder
(Sambucus nigra L.).
AB - The inflorescence of common elder (Sambucus nigra L., Adoxaceae) is known to be
rich in phenolic compounds. The content of five selected phenolic compounds
(rutin, chlorogenic acid, isoquercitrin, isorhamnetin-3-O- rutinoside and
dicaffeoylquinic acid) was determined in methanolic extracts from flowers and
floral stems by HPLC in samples obtained from 20 varieties of S. nigra cultivated
in Czech Republic. In all samples, there were determined rutin (11-54 mg/g),
chlorogenic acid (23-46 mg/g), isoquercitrin (0.6-18 mg/g), isorhamnetin-3-O
rutinoside (3-10 mg/g), calculated on air-dried material. The content of
dicaffeoylquinic acid was 0-13 mg/g of air-dried material. The amount of the
analysed compounds in floral stems was lower than the flowers. The results are a
unique set of information on the content of main phenolics in the inflorescence
of cultured elderberry varieties.
PMID- 27484409
TI - A novel approach to neonatal abdominal surgery via a circular incision around the
umbilical cord.
AB - We present a new, scarless, circular incisional approach around the umbilical
cord for neonates with intestinal atresia. This novel approach achieves truly
woundless surgery. It is simple, safe, and can be used for an intestinal surgical
treatment in neonates.
PMID- 27484406
TI - Regulation of centriolar satellite integrity and its physiology.
AB - Centriolar satellites comprise cytoplasmic granules that are located around the
centrosome. Their molecular identification was first reported more than a quarter
of a century ago. These particles are not static in the cell but instead
constantly move around the centrosome. Over the last decade, significant advances
in their molecular compositions and biological functions have been achieved due
to comprehensive proteomics and genomics, super-resolution microscopy analyses
and elegant genetic manipulations. Centriolar satellites play pivotal roles in
centrosome assembly and primary cilium formation through the delivery of
centriolar/centrosomal components from the cytoplasm to the centrosome. Their
importance is further underscored by the fact that mutations in genes encoding
satellite components and regulators lead to various human disorders such as
ciliopathies. Moreover, the most recent findings highlight dynamic structural
remodelling in response to internal and external cues and unexpected positive
feedback control that is exerted from the centrosome for centriolar satellite
integrity.
PMID- 27484410
TI - The outcomes of a frenulotomy on breastfeeding infants followed up for 3 months
at Thammasat University Hospital.
AB - PURPOSE: To study the effects of frenulotomy on nipple pain, latch and the
success in exclusive breastfeeding (EBF) at 3-month follow-up. METHODS: A
prospective cross-sectional study of 328 mother-infant pairs with both tongue-tie
and breastfeeding problems was performed. Nipple pain and latch were evaluated
using numeric rating scale and LATCH score, respectively, and compared between
pre and post-operatively at 24 h and 1 week. The success rate of EBF was assessed
at 3 months after frenulotomy. RESULTS: Nipple pain score were significantly
decreased (median difference = 3 and 4, P < 0.001) and LATCH score were
significantly increased (mean difference = 1.92 and 2.13, P < 0.001) at 24 h and
1 week post-operatively. At 3 months, a success rate of EBF was 66.67 %.
Multivariable analysis clustering by maternal age of 18 years was performed.
Factors that were significantly (P < 0.05) associated with the success were:
girls, age at surgery <=24 h, higher number of children in family, low birth
weight, tongue-tie severity, nipple grading, LATCH score >=8 and nipple sensation
at 1 week after surgery. CONCLUSION: Frenulotomy could significantly reduce
nipple pain and increase LATCH score in tongue-tied infants with breastfeeding
difficulty. Several factors are positively associated with the success of EBF.
Tongue-tie severity, LATCH score and nipple sensation were the factors that can
be modified by frenulotomy.
PMID- 27484411
TI - Classification of ankle joint movements based on surface electromyography signals
for rehabilitation robot applications.
AB - Electromyography (EMG)-based control is the core of prostheses, orthoses, and
other rehabilitation devices in recent research. Nonetheless, EMG is difficult to
use as a control signal given the complex nature of the signal. To overcome this
problem, the researchers employed a pattern recognition technique. EMG pattern
recognition mainly involves four stages: signal detection, preprocessing feature
extraction, dimensionality reduction, and classification. In particular, the
success of any pattern recognition technique depends on the feature extraction
stage. In this study, a modified time-domain features set and logarithmic
transferred time-domain features (LTD) were evaluated and compared with other
traditional time-domain features set (TTD). Three classifiers were employed to
assess the two feature sets, namely linear discriminant analysis (LDA), k nearest
neighborhood, and Naive Bayes. Results indicated the superiority of the new time
domain feature set LTD, on conventional time-domain features TTD with the average
classification accuracy of 97.23 %. In addition, the LDA classifier outperformed
the other two classifiers considered in this study.
PMID- 27484412
TI - Classifications In Brief: The Paprosky Classification of Femoral Bone Loss.
PMID- 27484413
TI - CORR Insights((r)): Shoulder Activity Level is Associated with Type of Employment
and Income in the Normative Population Without Shoulder Disorders.
PMID- 27484414
TI - Improving palliative care in selected settings in England using quality
indicators: a realist evaluation.
AB - BACKGROUND: There is a gap between readily available evidence of best practice
and its use in everyday palliative care. The IMPACT study evaluated the potential
of facilitated use of Quality Indicators as tools to improve palliative care in
different settings in England. METHODS: 1) Modelling palliative care services and
selecting a set of Quality Indicators to form the core of an intervention, 2)
Case studies of intervention using the Quality Indicator set supported by an
expert in service change in selected settings (general practice, community
palliative care teams, care homes, hospital wards, in-patient hospices) with a
before-and-after evaluation, and 3) realist evaluation of processes and outcomes
across settings. Participants in each setting were supported to identify no more
than three Quality Indicators to work on over an eight-month period in 2013/2014.
RESULTS: General practices could not be recruited to the study. Care homes were
recruited but not retained. Hospital wards were recruited and retained, and using
the Quality Indicator (QI) set achieved some of their desired changes. Hospices
and community palliative care teams were able to use the QI set to achieve almost
all their desired changes, and develop plans for quality improvements.
Improvements included: increasing the utility of electronic medical records,
writing a manual for end of life care, establishing working relationships with a
hospice; standardising information transfer between settings, holding regular
multi-disciplinary team meetings, exploration of family carers' views and
experiences; developing referral criteria, and improvement of information
transfer at patient discharge to home or to hospital. Realist evaluation
suggested that: 1) uptake and use of QIs are determined by organisational
orientation towards continuous improvement; 2) the perceived value of a QI
package was not powerful enough for GPs and care homes to commit to or sustain
involvement; 3) the QI set may have been to narrow in focus, or more specialist
than generalist; and 4) the greater the settings' 'top-down' engagement with this
change project, the more problematic was its implementation. CONCLUSIONS: Whilst
use of QIs may facilitate improvements in specialist palliative care services,
different QI sets may be needed for generalist care settings.
PMID- 27484415
TI - Measurement of Uranium Isotope Ratios in Keratinous Materials: A Noninvasive
Bioassay for Special Nuclear Material.
AB - Hair, toenail, and fingernail are noninvasive, integrative biological monitors
routinely used to assess mineral intake.1-4 In this study, we demonstrate the
feasibility of distinguishing between exposure to natural, depleted, and enriched
U by measuring the (235)U/(238)U, (234)U/(238)U, and (236)U/(238)U ratios in the
hair, fingernails, and toenails of occupationally exposed workers and control
volunteers. The exposure history of cases and controls to non-natural U was
assessed through voluntary self-reporting using a simple questionnaire. The
measured U isotope ratios and U concentration in the hair, toenail, and
fingernail of cases were compared to a nonexposed control group. No difference
was observed in the uranium concentration between the two groups. Significant
differences between the cases and the control group were observed in the
(235)U/(238)U and (236)U/(238)U isotope ratios but not the (234)U/(238)U. This is
the first time that hair, fingernail, and toenail have been demonstrated to be
sensitive to occupational exposure to enriched and depleted U, a result with
significant implications for proliferation compliance monitoring.
PMID- 27484417
TI - [Aggression and restlessness following baclofen overdose: the narrow line between
intoxication and withdrawal symptoms].
AB - BACKGROUND: Baclofen is increasingly prescribed for alcohol dependency.
Subsequently, the risk of self-intoxication with this medicinal product is
increasing. CASE DESCRIPTION: A 23-year-old man with a history of alcohol
dependence was admitted to our hospital after self-intoxication with 2700 mg
baclofen and 330 mg mirtazapine. Respiratory insufficiency as a result of the
baclofen intoxication required intubation and admission to the ICU. During the
first day, despite the use of sedatives, the patient became intermittently
agitated and aggressive. In the following days, he developed severe delirium,
probably due to baclofen withdrawal. The reintroduction of baclofen quickly
resolved these symptoms. CONCLUSION: In the case of baclofen, in practice it is
difficult to differentiate between intoxication and withdrawal. To prevent
potentially severe withdrawal symptoms, we recommend reintroduction of baclofen
when the first signs of restlessness and agitation arise following intoxication.
PMID- 27484416
TI - Repurposing FDA-approved drugs for anti-aging therapies.
AB - There is great interest in drugs that are capable of modulating multiple aging
pathways, thereby delaying the onset and progression of aging. Effective
strategies for drug development include the repurposing of existing drugs already
approved by the FDA for human therapy. FDA approved drugs have known mechanisms
of action and have been thoroughly screened for safety. Although there has been
extensive scientific activity in repurposing drugs for disease therapy, there has
been little testing of these drugs for their effects on aging. The pool of FDA
approved drugs therefore represents a large reservoir of drug candidates with
substantial potential for anti-aging therapy. In this paper we employ
FINDSITEcomb, a powerful ligand homology modeling program, to identify binding
partners for proteins produced by temperature sensing genes that have been
implicated in aging. This list of drugs with potential to modulate aging rates
was then tested experimentally for lifespan and healthspan extension using a
small invertebrate model. Three protein targets of the rotifer Brachionus
manjavacas corresponding to products of the transient receptor potential gene 7,
ribosomal protein S6 polypeptide 2 gene, or forkhead box C gene, were screened
against a compound library consisting of DrugBank drugs including 1347 FDA
approved, non-nutraceutical molecules. Twenty nine drugs ranked in the top 1 %
for binding to each target were subsequently included in our experimental
analysis. Continuous exposure of rotifers to 1 uM naproxen significantly extended
rotifer mean lifespan by 14 %. We used three endpoints to estimate rotifer
health: swimming speed (mobility proxy), reproduction (overall vitality), and
mitochondria activity (cellular senescence proxy). The natural decline in
swimming speed with aging was more gradual when rotifers were exposed to three
drugs, so that on day 6, mean swimming speed of females was 1.19 mm/s for
naproxen (P = 0.038), 1.20 for fludarabine (P = 0.040), 1.35 for hydralazine (P =
0.038), as compared to 0.88 mm/s in the control. The average reproduction of
control females in the second half of their reproductive lifespan was 1.08 per
day. In contrast, females treated with 1 uM naproxen produced 1.4 offspring per
day (P = 0.027) and females treated with 10 uM fludarabine or 1 uM hydralazine
produced 1.72 (P = <0.001) and 1.66 (P = 0.001) offspring per day, respectively.
Mitochondrial activity naturally declines with rotifer aging, but B. manjavacas
treated with 1 uM hydralazine or 10 uM fludarabine retained 49 % (P = 0.038) and
89 % (P = 0.002) greater mitochondria activity, respectively, than untreated
controls. Our results demonstrate that coupling computation to experimentation
can quickly identify new drug candidates with anti-aging potential. Screening
drugs for anti-aging effects using a rotifer bioassay is a powerful first step in
identifying compounds worthy of follow-up in vertebrate models. Even if lifespan
extension is not observed, certain drugs could improve healthspan, slowing age
dependent losses in mobility and vitality.
PMID- 27484418
TI - [The unresponsive wakefulness syndrome: Dutch perspectives].
AB - The unresponsive wakefulness syndrome (UWS), formerly known as the vegetative
state, is one of the most dramatic outcomes of acquired brain injury. Patients
with UWS open their eyes spontaneously but demonstrate only reflexive behavior;
there are no signs of consciousness. Research shows that, for years now, the
Netherlands has the world's lowest documented prevalence of UWS. Unfortunately,
this small group of vulnerable patients does not receive the care it needs.
Access to specialized rehabilitation is limited, misdiagnosis rates are high and
a substantial number of UWS patients receive life-prolonging treatment beyond
chances of recovery, despite a framework allowing for discontinuation of such
treatment once recovery of consciousness has become unlikely. By comparing data
from 2012 with that of 2003, this paper illustrates the current situation and
outlook for UWS patients in the Netherlands and makes recommendations for the
optimization of treatment and care, as well as for future research.
PMID- 27484419
TI - [Skin to skin contact and breast-feeding after birth: not always without risk!].
AB - Skin-to-skin contact after birth is propagated to facilitate breast-feeding and
mother-child bonding. We describe two term infants with sudden unexpected
postnatal collapse (SUPC) during skin-to-skin contact. The infants were found
with abnormal colour, hypotonia and apnoea, in a prone position on the chest of
their mothers, both of whom were primipara with a high BMI. After stimulation,
both infants recovered completely. No specific potential cause, other than the
position, could be found. These cases illustrate that skin-to-skin contact after
birth is not without risk. In available literature, risk factors for SUPC include
primiparity and infant orientation such as prone and lateral positions. These
positions are also risk factors for sudden infant death syndrome (SIDS). To
improve safety, a primipara should be supervised during skin-to-skin contact and
not be left alone in the first hours after delivery; the infant should be
guaranteed a free airway, especially when the mother has a high BMI.
PMID- 27484420
TI - [Kleine Levin Syndrome: more than just periodic hypersomnia].
AB - BACKGROUND: Kleine Levin Syndrome (KLS) is a rare disease with periodic
hypersomnia as its main feature. Hyperphagia and hypersexuality are also
described as classical symptoms, although quite recently it has become clear that
the full triad is absent in the majority of patients. CASE DESCRIPTION: A 14-year
old boy developed KLS after a period of flu-like symptoms. Over the course of
three years he suffered from seven one-week episodes of extreme hypersomnia
(sleeping 18 hours a day), depersonalisation, apathy, anxiety, paranoia,
confusion, hallucinations and uninhibited sexual behaviour. He ate little.
Ancillary investigations did not reveal any abnormalities. In between these
episodes he had no symptoms. CONCLUSION: From this case description and a summary
of the symptoms of twelve other patients with KLS, it appears that
neuropsychiatric symptoms are much more prominent than hyperphagia and
hypersexuality. It is important that the typical KLS phenotype be reappraised, so
that the condition can be recognised early and patients managed appropriately.
PMID- 27484421
TI - [The placebo effects of good communication].
AB - - Good communication is important for patients and can elicit placebo effects:
true psychobiological effects not attributable to the medical-technical
intervention.- It is, however, often unclear which communication behaviours
influence specific patient outcomes.- In this article we present insights into
the potential effect of specific communication, via specific mechanisms, on
specific patient outcomes, including patients' perception of pain.- A recent
systematic review and additional literature demonstrate that (a) manipulating
patients' expectations, (b) demonstrating empathy, and (c) providing procedural
information, might influence patient outcomes.- These placebo effects probably
occur via (a) neurobiological responses comparable to the effects of pain
medication, (b) reduction of anxiety and stress, and
PMID- 27484422
TI - [A woman with a cavity in an intervertebral disc on the CT-scan].
AB - The CT scan of a 77-year-old woman showed hypodense structures in the spine
called vacuum phenomenon as an incidental finding. The cause in the majority of
cases is the degeneration of tissue but vacuum phenomenon is also associated with
other disorders. It is important to distinguish between benign causes and
malignant causes. Unfamiliarity with this vacuum phenomenon may lead to
suboptimal treatment.
PMID- 27484423
TI - [Photo stories instead of leaflets: support for people with low health literacy].
AB - In the Netherlands, almost 30 percent of adults have limited levels of health
literacy. They have difficulties finding, understanding and using health
information. Comprehensible health information is extra important for people with
low health literacy. A systematic review revealed that narrative health
communication is a promising strategy to increase comprehension. We have
investigated which interventions may improve comprehensibility of health-related
documents for older adults with different levels of health literacy. We are
currently exploring if and how photo stories on care and health topics can
support people with low health literacy.
PMID- 27484424
TI - [A girl with a cold foot].
AB - A 14-year-old girl presented with a progressively cold, pale foot. Pedal pulses
were absent and there was sensory and motor loss. CT angiography revealed a
thromboembolic occlusion of the crural arteries and a popliteal artery
entrapment. Following thromboembolectomy with popliteal artery patch angioplasty
and release of the gastrocnemius muscle, the girl fully recovered.
PMID- 27484425
TI - [Practice assistant sometimes misses urgent request for help: telephone triage in
general practice].
AB - OBJECTIVE: To assess the organisation and appropriateness of telephone triage in
general practices in the Netherlands. DESIGN: Cross-sectional observational
study. METHODS: Via e-mail we invited all members of the Dutch Association of
practice assistants to complete an online survey. The questionnaire included
questions about practice assistants' background characteristics and the
practices' triage organisation. Furthermore, they were asked to assess the
indicated type of care for a number of fictive case scenarios involving a variety
of health problems and levels of urgency. To determine the appropriateness of the
respondents' assessments, each was compared to a reference standard agreed by
experts. In addition, the association between practice assistants' background
characteristics and organizational setup of the triage organisation with the
appropriateness of triage was examined. RESULTS: The response rate was 41.1%
(N=973). The required care was assessed appropriately in 63.6% of the cases, over
estimated in 19.3% and under-estimated in 17.1% of cases. The sensitivity of
identifying patients with a highly urgent problem was 76.7%, whereas the
specificity was 94.0%. The appropriateness of the assessments of the required
care was higher for more experienced assistants and assistants with regular daily
work meetings with the GP. Triage training, use of a triage tool and
authorization of advice provision were not associated with appropriateness of
triage. CONCLUSION: Triage by practice assistants in general practices is
efficient, but potentially unsafe in highly urgent cases. It is therefore
important to train practice assistants in the identification of highly urgent
cases.
PMID- 27484426
TI - [Supervisors being assessed].
AB - OBJECTIVE: Since 2015, a permanent quality cycle is mandatory for medical
residency specialist training. One aspect of this cycle is the System for
Evaluation of Teaching Qualities (SETQ), which allows trainees to give feedback
about their supervisor. We analysed how these quality evaluations are discussed
within groups of supervisors. DESIGN: Questionnaire study amongst residency
training program directors. METHOD: From September 2013 till February 2014, an
online questionnaire was distributed amongst 255 program directors of medical
residency specialist training in 54 teaching hospitals. The questionnaire
assessed (a) if feedback was discussed, (b) the purpose of the feedback
discussions, (c) their format, (d) the perceived outcomes and (e) any need for
supervisor support in relation to any future feedback discussions. RESULTS: The
response rate for the questionnaire was 61%. The majority of supervisor groups
(86%) followed up on their individual SETQ feedback. Formats included
individually between the program director and supervisor (34%), in a peer group
of supervisors (69%), and in group format involving both trainees and supervisors
(68%). Respondents listed the mutual learning process and devising improvement
plans as aims of discussing feedback in a group format. There is considerable
variation between groups of supervisors in terms of how the feedback is
discussed. Over fifty percent of the group discussions resulted in concrete
agreements for improvement plans. CONCLUSION: The feedback by trainees on the
teaching performance of their supervisors is not wasted. The vast majority of
supervisors follow up on their teaching performance feedback in peer group
meetings.
PMID- 27484427
TI - [A man with slowly progressive dyspnea on exertion].
AB - A 42-year-old man with a medical history of liver cirrhosis and portal
hypertension was admitted to the hospital because of slowly progressive shortness
of breath and hypoxemia. The diagnosis hepatopulmonary syndrome was confirmed by
a pulmonary perfusion scan with 99m Tc-albumin. The scan showed a right-left
shunt, because the 99m Tc-albumin transited the lungs and appeared in the brain,
the thyroid gland, the kidneys and the spleen. The patient received a liver
transplantation, which is considered the only definitive treatment.
PMID- 27484428
TI - [A woman with abdominal pain and retroperitoneal free air].
AB - A 62-year-old female was admitted to the hospital with pain in the lower abdomen
and fever since 1 week. A CT scan showed retroperitoneal air around the inferior
mesenteric vein and diverticulitis of the sigmoid. We made the diagnosis of
intramesocolic diverticular perforation of the sigmoid, a rare phenomenon, and
performed an emergency sigmoidectomy.
PMID- 27484429
TI - [Big data, Roemer's law and avoidable hospital admissions].
AB - From an analysis of data from 23 European countries to determine the impact of
primary care on avoidable hospital admissions for uncontrolled diabetes it
appeared that, contrary to expectation, countries with strong primary care did
not have a lower rate of avoidable hospital admission. It is clear that Roemer's
law, 'a bed built is a bed filled,' still applies. However, the validity of this
sort of analysis can be questioned, as these data are highly aggregated, and
registration quality differs between countries. It is also questionable if these
datasets can be considered as 'big data' as there are relatively small numbers
per country. Big data analyses are useful for discerning patterns and formulating
hypotheses, but not for proving causality. An unwanted side effect of this kind
of analysis might be that policymakers use these not so valid results to underpin
their policy to their advantage.
PMID- 27484430
TI - [Triage in primary care: overkill?].
AB - Based on triage during out-of-hours emergency services with physical contact with
patients, the Dutch Triage Standard - a telephone triage algorithm - has been
developed for use in primary care out-of-hours services. However, it is also used
in the daytime setting. We argue that this tool should be evaluated by actually
evaluating the telephone contacts that are backed up during triage and using the
final diagnoses of these contacts as the reference standard. We have serious
doubts whether the Dutch Triage Standard is an effective tool in the primary care
daytime setting with its very low prevalence of high urgency. Adequate triage is
time consuming, and may result in reduced accessibility thus creating critical
situations. Well-evaluated pilots should precede large-scale implementation of
decision support systems.
PMID- 27484431
TI - ['Primum non nocebo' and the obligatory placebo; how can we better please the
patient?].
AB - There is ample evidence to support the notion that the context of a treatment
influences the efficacy of that treatment. Most doctors feel uncomfortable with
the intentional introduction of contextual elements that have no plausible
biological effect, because it is not in line with their biomechanical world view
and training. Withholding certain information to prevent nocebo effects may even
go against our duty to inform patients. We argue that our primary duty is to
serve the interest of our patients and that to withhold positive contextual
elements or to introduce negative contextual elements conflicts with this duty.
PMID- 27484432
TI - [Practice guideline 'Urinary incontinence in women' from the Dutch College of
General Practitioners].
AB - - The Dutch College of General Practitioners' (NHG) practice guideline 'Urinary
incontinence in women' provides guidelines for diagnosis and management of
stress, urgency and mixed urinary incontinence in adult women.- General
practitioners (GPs) should be alert to signals for urinary incontinence in women
and offer active diagnosis and treatment if necessary.- Shared decision making is
central in the guideline; the GP and the patient should discuss therapeutic
options and decide on treatment policy in mutual consultation.- Women with stress
urinary incontinence can choose between pelvic floor exercises or a pessary as
initial treatment. Placing a midurethral sling (MUS) will be discussed if initial
treatment is insufficiently effective or in the case of serious symptoms.- When
bladder training is ineffective in urgency incontinence, the GP will discuss the
pros and cons of adding an anticholinergic agent.- Exercise therapy can take
place in the GPs practice or under supervision of a pelvic physical therapist.
PMID- 27484433
TI - Molecular mechanisms of experience-dependent structural and functional plasticity
in the brain.
AB - Experiences and environments have a variety of effects on brain plasticity at
levels ranging from the molecular and cellular to the behavioral. Brain
plasticity is one of the most important characteristics of animal survival. In
particular, environmental enrichment and exercise induce many structural and
functional changes in the brain, and it is noteworthy that these changes result
in further beneficial effects at behavioral levels, such as improved learning
behavior and antidepressant effects. The effects of enrichment and exercise, and
the mechanisms involved in both, provide crucial evidence for the prevention and
treatment of brain disorders. However, the enriched environment- and exercise
induced mechanisms underlying the structural and behavioral effects in the brain
remain poorly understood. In this review I discuss the molecular mechanisms of
environment- and experience-dependent brain plasticity based on the results of
studies carried out by our research group at the Department of Neuroscience and
Cell Biology, Osaka University. This review consists of three parts: first, a
description of a role for the motor protein KIF1A in enhanced synaptogenesis and
memory function induced by environmental enrichment; second, a discussion of the
function of the 5-HT3 receptor in hippocampal neurogenesis and behavioral changes
induced by exercise; third, a discussion of the role of the 5-HT3 receptor in
fear extinction.
PMID- 27484434
TI - Exercise-induced hypoalgesia: potential mechanisms in animal models of
neuropathic pain.
AB - Physical exercise, such as forced treadmill running and swimming, can
sufficiently improve mechanical allodynia and heat hyperalgesia in animal models
of neuropathic pain (NPP), including partial sciatic nerve ligation, chronic
constriction injury, and spinal nerve ligation models. Thus, physical exercise
has been established as a low-cost, safe, and effective way to manage NPP
conditions, but the exact mechanisms underlying such exercise-induced hypoalgesia
(EIH) are not fully understood. A growing body of evidence has identified several
factors that work at different levels of the nervous system as playing important
roles in producing EIH in animal models of NPP. The objective of this review is
to provide an overview of key players associated with EIH, and then to discuss
our current understanding of the mechanisms underlying EIH. Relevant studies have
demonstrated that physical exercise can dramatically alter the levels of
inflammatory cytokines, neurotrophins, neurotransmitters, endogenous opioids, and
histone acetylation at various sites in the nervous system, such as injured
peripheral nerves, dorsal root ganglia, and spinal dorsal horn in animal models
of NPP, thereby contributing to the production of EIH. These results suggest that
EIH is produced through multiple cellular and molecular events in the pain
pathway.
PMID- 27484435
TI - Endohedral dynamics of push-pull rotor-functionalized cages.
AB - A series of [Pd2L4] coordination cages featuring endohedral functionalities in
central backbone positions was synthesized. Although attached via C[double bond,
length as m-dash]C double bonds, the substituents behave as molecular rotors.
This is explained by their pronounced donor-acceptor character which lowers
rotational barriers and allows for electronic control over the spinning rates
inside the cage. The dynamic behaviour of the free ligands, assembled cages and
host-guest complexes is compared with the aid of NMR experiments, X-ray structure
analysis and molecular modelling.
PMID- 27484436
TI - Comparison of concurrent treatment with vitamin K2 and risedronate compared with
treatment with risedronate alone in patients with osteoporosis: Japanese
Osteoporosis Intervention Trial-03.
AB - The aim of this study was to investigate the efficacy of concurrent treatment
with vitamin K2 and risedronate compared with treatment with risedronate alone in
patients with osteoporosis and to explore subsets of patients for which
concurrent treatment is particularly efficacious. Women with osteoporosis aged 65
years or older were recruited from 123 institutes in Japan and allocated to take
either vitamin K2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or
risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the
incidence of any fracture (vertebral and nonvertebral). The secondary end points
were bone mineral density, height, undercarboxylated osteocalcin concentration,
quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral
fractures occurred in 117 or 22 sites respectively among 931 patients in the
risedronate and vitamin K2 group and in 104 or 26 sites respectively among 943
patients in the risedronate alone group. The rates of any incident fracture were
similar between the two groups (incidence rate ratio 1.074, 95 % confidence
interval 0.811-1.422, p = 0.62), implying that the primary end point was not met.
There were no differences in the degree of increase in bone mineral density
between the two groups. Undercarboxylated osteocalcin concentration decreased
from 5.81 +/- 3.93 ng/mL to 2.59 +/- 1.52 ng/mL at 6 months in the risedronate
and vitamin K2 group, whereas the change in the risedronate alone group was
minimal (from 5.96 +/- 4.36 ng/mL to 4.05 +/- 3.40 ng/mL at 6 months) (p < 0.01).
The treatment discontinuation rate was higher in the risedronate and vitamin K2
group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse
drug reactions were reported. In conclusion, concurrent treatment with vitamin K2
and risedronate was not efficacious compared with monotherapy with risedronate in
terms of fracture prevention.
PMID- 27484439
TI - Prevalence of depression in patients of type 2 diabetes mellitus: A cross
sectional study in a tertiary care centre.
AB - AIMS: The present study aims to study the prevalence of depression in patients
with uncomplicated type II diabetes mellitus and to find its association with
various socio-demographic factors in the same. MATERIALS AND METHODS: A cross
sectional, single interview study was performed in an outpatient department of an
endocrinology institute. Total 80 type II DM patients without any associated
complications of diabetes were included in this study. To diagnose Depressive
Episode, structured clinical interview for DSM V was applied. Severity of
depression was assessed by Hamilton Rating Scale for Depression (HAM-D). To
assess socio-demographic characteristics of the patients, all of them were
evaluated with a semi-structured socio-demographic performa. RESULTS: 38.75%
patients (N=31) were found to be suffering from depression. Among them 48.38%
were moderately depressed and none were suffering from very severe depression.
Significant association was not found between depression and socio-demographic
factors of age (p=0.920), gender (p=0.251), economic profile (p=0.583), local
background of the patient (p=0.646), educational qualification (p=0.935) and
marital status (p=0.644). Similarly no association was found with duration of
diabetes, HbA1c and BMI. CONCLUSION: Exclusion of complicated cases didn't seem
to influence overall prevalence of depression, although reduction in severity was
apparent. Thus even in those diabetic patients who are leading a complication
free life, a detailed psychiatric analysis to rule out depression is mandatory.
PMID- 27484437
TI - The Effects of Supplementation with p-Synephrine Alone and in Combination with
Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance
Exercise.
AB - OBJECTIVE: The purpose of this study was to examine the metabolic, lipolytic, and
cardiovascular responses to supplementation with p-synephrine alone and in
combination with caffeine during resistance exercise (RE). METHODS: Twelve
healthy men performed a control RE protocol (6 * 10 repetitions of squats) and
were randomly assigned (using a double-blind crossover design with random
protocol sequencing) to a supplement sequence: p-synephrine (S; 100 mg), p
synephrine + caffeine (SCF; 100 mg of p-synephrine plus 100 mg of caffeine), or a
placebo (P). Subjects reported to the lab at a standard time, consumed a
supplement, sat quietly for 45 minutes, performed the RE protocol, and sat
quietly for 30 minutes. Blood samples were collected at rest (T1), after sitting
quietly for 45 minutes (T2), immediately following RE (T3), and 15 minutes (T4)
and 30 minutes (T5) postexercise. Oxygen consumption (VO2) and heart rate (HR)
data were collected throughout. RESULTS: Serum glycerol was significantly
elevated at T2 only in S and SCF and T3 to T5 in all treatments. Nonesterified
fatty acid (NEFA) concentrations did not differ between treatments. Plasma
glucose was significantly elevated compared to T1 with highest area under the
curve values seen in SCF. Mean VO2 and energy expenditure (EE) were significantly
higher in S and SCF through 30 minutes postexercise. Fat oxidation rates favored
S and SCF between 25 and 30 minutes postexercise. Mean HR during RE was
significantly highest in SCF. CONCLUSIONS: Supplementation with S and SCF
increases lipolysis primarily at rest and increases VO2, EE, and fat oxidation
rates 30 minutes following RE. No HR changes were observed unless caffeine was
added.
PMID- 27484441
TI - Effect of omega-3 fatty acids supplementation on insulin resistance in women with
polycystic ovary syndrome: Meta-analysis of randomized controlled trials.
AB - BACKGROUND: Several studies have shown that omega-3 polyunsaturated fatty acids
(PUFA) may improve insulin resistance in various diseases. However, the possible
effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
supplementation on insulin resistance in PCOS still remains unclear. We evaluated
the effect of omega-3 PUFA supplementation on insulin resistance in women with
PCOS in a meta-analysis. METHODS: Literature searches of MEDLINE, PubMed Central
and EMBASE for publications in English were conducted up to December 2015. We
included all randomized controlled trials (RCTs) that investigated effects of
omega-3 fatty acids supplements on insulin resistance in women with PCOS. Results
are summarized as mean differences (MD) with 95% confidence intervals (CI).
Effect sizes of eligible studies were pooled using random-effects models (the
DerSimonian-Laird estimator). We assessed the potential sources of heterogeneity
using the standard chi2 test. RESULTS: Of 1202 papers, three RCTs were eligible
for inclusion which involved 72 cases and 73 controls. The dose range for omega3
supplement was 1.2g to 3.6g and the duration of follow-up was from 6 to 8 weeks.
There was no significant effect of omega-3 fatty acids supplements compared to
placebo on insulin resistance (MD: 6.18; CI; -3.347, 15.382; p=0.208) and HOMA
IR (MD: 0.276; 95% CI=-1.428, 1.981; p=0.751) in women with PCOS. CONCLUSION: The
results provide an evidence that supplementation with omega-3 fatty acids may not
have a beneficial effect on improving insulin resistance in women with PCOS.
PMID- 27484440
TI - A study on comparative efficacy and cost effectiveness of Pregabalin and
Duloxetine used in diabetic neuropathic pain.
AB - AIM: The study was designed for comparing the efficacy and cost effectiveness of
Pregabalin and Duloxetine used in Diabetic Neuropathic Pain. METHODS: The
prospective interventional 6 month study was conducted in a diabetic clinic of a
500 bedded tertiary care hospital in South India. The subjects having diagnosed
with diabetic neuropathy and not treated with Pregabalin and Duloxetine or any
other drugs of its class were selected. The data were collected using NPS and
Neuro QoL questionnaires. The cost of both drugs used in the study was calculated
as the mean of the price of 3 leading common brands of those drugs. The
comparative efficacy was calculated by comparing the mean difference produced by
both drugs in NPS and QoL scores. The cost effectiveness were calculated by ICER
ratio. RESULTS: The results have shown a significant improvement in the mean
difference of NPS and Neuro QoL scores of both Pregabalin (p=<0.001) and
Duloxetine (p=<0.001) before and after the therapy, the Duloxetine dominates over
Pregabalin in both. The mean cost of Pregabalin for 3 months therapy was found to
be INR 668.7 and that for Duloxetine was INR 756. Duloxetine showed a better
effect but more expensive. ICER ratio was calculated and found that a cost of INR
61.47 per extra QoL gained by Duloxetine. CONCLUSION: The study have revealed
that, both drugs are found to be effective.On conducting cost effective analysis,
a significant better improvement in QoL of patients was obtained by Duloxetine
with comparatively mild increase in the price.
PMID- 27484443
TI - The first organocopper tetrazole derivative: synthesis and characterization.
AB - 1-(5-Amino-3-azapentyl)tetrazole dihydrochloride (HL.2HCl) was prepared by
heterocyclization of diethylenetriamine with triethyl orthoformate and sodium
azide followed by treatment with potassium carbonate and hydrochloric acid. The
reaction of CuCl2, HL.2HCl and triethylamine (NEt3) in a molar ratio of 1 : 1 : 3
in water was found to generate a novel organometallic tetrazole derivative
Cu2L2Cl2. This compound is present as a binuclear centrosymmetric molecular
complex, in which C-deprotonated tetrazole L acts as a chelating ligand via the
two amino N and tetrazole ring C coordination sites and the two copper atoms are
linked together through two tetrazole ring N(4)-C(5) bridges. This complex is the
first organocopper tetrazole derivative. When the molar ratio of the reagents in
the abovementioned reaction was changed to 1 : 2 : 2, the complex Cu(HL)2Cl2 was
formed along with Cu2L2Cl2. Pure Cu(HL)2Cl2 was isolated after reaction of the
reagents in a molar ratio of 1 : 3 : 6. The complex Cu(HL)2Cl2 is present as a
mononuclear molecular complex, with a chelating coordination mode of HL via the
two amino N atoms only. Both complexes as well as HL.2HCl were characterized by
single-crystal X-ray analysis.
PMID- 27484442
TI - Automated assignment of NMR chemical shifts based on a known structure and 4D
spectra.
AB - Apart from their central role during 3D structure determination of proteins the
backbone chemical shift assignment is the basis for a number of applications,
like chemical shift perturbation mapping and studies on the dynamics of proteins.
This assignment is not a trivial task even if a 3D protein structure is known and
needs almost as much effort as the assignment for structure prediction if
performed manually. We present here a new algorithm based solely on 4D
[(1)H,(15)N]-HSQC-NOESY-[(1)H,(15)N]-HSQC spectra which is able to assign a large
percentage of chemical shifts (73-82 %) unambiguously, demonstrated with proteins
up to a size of 250 residues. For the remaining residues, a small number of
possible assignments is filtered out. This is done by comparing distances in the
3D structure to restraints obtained from the peak volumes in the 4D spectrum.
Using dead-end elimination, assignments are removed in which at least one of the
restraints is violated. Including additional information from chemical shift
predictions, a complete unambiguous assignment was obtained for Ubiquitin and 95
% of the residues were correctly assigned in the 251 residue-long N-terminal
domain of enzyme I. The program including source code is available at
https://github.com/thomasexner/4Dassign .
PMID- 27484444
TI - Recurrent Ventricular Tachycardia and Peripheral Gangrene in a Young Child.
AB - A 10-year-old girl presented with sudden onset recurrent ventricular tachycardia
and symmetrical distal peripheral gangrene. She also had pulmonary
thromboembolism and cerebral sinus venous thrombosis. Investigations revealed
anemia, hemolysis, hypocomplementemia, and elevated IgM anti-beta2 glycoprotein
antibody levels. Electrocardiogram and echocardiogram suggested features of a
rare cardiac anomaly, which was confirmed at autopsy.
PMID- 27484445
TI - Cultivating Lifelong Learning Skills During Graduate Medical Training.
AB - Lifelong learning is referred to as learning practiced by the individual for the
whole life, is flexible, and is accessible at all times. Medical Council of India
has included lifelong learning as a competency in its new regulations for
graduate medical training. Acquisition of metacognitive skills, self-directed
learning, self-monitoring, and reflective attitude are the main attributes of
lifelong learning; and all of these can be inculcated in the students by using
appropriate instructional methodologies. It is time to deliberate upon the
instructional designs to foster the lifelong learning skills and behaviors in
medical graduates. In this communication, we aim to debrief the concept of
lifelong learning, particularly in context with medical training and detailing
the process that can be explicitly used to cultivate the attitude of lifelong
learning in medical graduates.
PMID- 27484446
TI - Risk Factors for Central line associated Bloodstream Infections.
AB - OBJECTIVE: To carry out surveillance of central line associated bloodstream
infections in a Pediatric intensive care unit (PICU) and determine associated
risk factors. METHODS: This prospective study was conducted over 1.5 years in the
PICU. CDC definitions for these infections were followed and associated risk
factors were identified. RESULTS: Of 265 enrolled children with central line, 13
developed blood stream infections (incidence density 5.03/1000 central line
days). Significant risk factors included changing the central-line, especially
triple lumen, and frequently accessing the central line. CONCLUSION: Central line
associated bloodstream infections are preventable primary bacteremias and
intervention strategies for prevention should be based on evidence generated to
devise future protocols.
PMID- 27484447
TI - Xpert MTB/RIF for Diagnosis of Tuberculosis and Drug Resistance in Indian
Children.
PMID- 27484448
TI - Maternal Age at Childbirth and Perinatal and Under five Mortality in a
Prospective Birth Cohort from Delhi.
AB - OBJECTIVE: To evaluate the relationship between maternal age at child birth, and
perinatal and under-five mortality. DESIGN: Prospective birth cohort. SETTING:
Urban community. PARTICIPANTS: 9169 pregnancies in the New Delhi Birth Cohort
resulted in 8181 live births. These children were followed for survival status
and anthropometric measurements at birth (+3 days), 3,6,9 and 12 months (7 days),
and every 6 months thereafter until 21 years age. Information on maternal age at
child birth and socio-demographic profile was also obtained. OUTCOME MEASURES:
Offspring mortality from 28 weeks gestation till 5 years age. RESULTS: Offspring
mortality (stillbirths - 5 years; n=328) had a U-shaped association with maternal
age (P<0.001). Compared to the reference group (20-24 years), younger (<=19
years) and older (>=35 years) maternal ages were associated with a higher risk of
offspring mortality (HR: 1.68; 95% CI 1.16, 2.43 and HR 1.48; 95% CI 1.01, 2.16,
respectively). In young mothers, the increased risk persisted after adjustment
for socio-economic confounders (maternal education, household income and wealth;
HR 1.51; 95% CI 1.03, 2.20) and further for additional behavioral (place of
delivery) and biological mediators (gestation and birthweight) (HR 2.14; 95% CI
1.25,3.64). Similar associations were documented for post-perinatal deaths but
for perinatal mortality the higher risk was not statistically significant (P
>0.05). In older mothers, the increased mortality risk was not statistically
significant (P >0.05) after adjustment for socio-economic confounders.
CONCLUSION: Young motherhood is associated with an increased risk of post
perinatal mortality and measures to prevent early childbearing should be
strengthened.
PMID- 27484449
TI - Point of Care Neonatal Ultrasound - Head, Lung, Gut and Line Localization.
AB - CONTEXT: Knowledge and skills of heart, head, lung, gut and basic abdominal
ultrasound is of immense utility to clinicians in their day-to-day patient
management, and in acute events, in the absence of specialist service back-up.
This review examines the potential role of clinician-performed ultrasound in the
neonatal intensive care unit. EVIDENCE ACQUISITION: The bibliographic search of
English-language literature was performed electronically using PubMed and EMBASE
databases for the different topics we have covered under this review. RESULTS:
Bedside head ultrasound can be used to identify and screen for intraventricular
hemorrhage, periventricular leukomalacia and post-hemorrhagic ventricular
dilatation. It is also a useful adjuvant tool in the evaluation of hypoxic
ischemic encephalopathy. The relatively new lung ultrasound technique is useful
in identifying transient tachypnea, pneumonia, pneumothorax, fluid overload and
pleural effusion. Gut ultrasound is useful in identifying necrotizing
enterocolitis and probably is better than X-ray in prognostication. Ultrasound is
also useful in identifying vascular line positions without radiation exposure.
MAIN CONCLUSIONS: Ultrasound performed by the clinician has an extensive role in
the neonatal intensive care unit. Basic ultrasound knowledge of head, lung and
gut is a useful supplement to clinical decision-making.
PMID- 27484450
TI - Ineffective correction of PPARgamma signaling in cystic fibrosis airway
epithelial cells undergoing repair.
AB - Peroxisome proliferator-activated receptor gamma (PPARgamma) represents a
potential target to treat airway mucus hypersecretion in cystic fibrosis (CF). We
aimed to determine if PPARgamma is altered in CF human airway epithelial cells
(HAECs), if PPARgamma contributes to mucin expression and HAEC differentiation,
and if PPARgamma ligand therapy corrects the CF phenotype. To this end, well
differentiated CF and NCF HAEC primary cultures were wounded to monitor the
expression of key genes involved in PPARgamma activation and mucus homeostasis,
and to evaluate the effect of a PPARgamma agonist, at different times of repair.
Hydroxyprostaglandin dehydrogenase (HPGD) converts prostaglandin E2 to 15-keto
PGE2 (15kPGE2), an endogenous PPARgamma ligand. Interestingly, PPARgamma and HPGD
expression dramatically decreased in CF HAECs. These changes were accompanied by
an increase in the expression of MUC5B. The correlation between PPARgamma and
MUC5B was confirmed in an airway epithelial cell line after CFTR knock-down.
Exposure of HAECs to 15kPGE2 did not correct the CF phenotype but revealed a
defect in the process of basal cell (BC) differentiation. The HPGD/PPARgamma axis
is deregulated in primary HAEC cultures from CF patients, which may impact the
maturation of BCs to differentiated luminal cells. Importantly, PPARgamma therapy
was inefficient in correcting the CF defect.
PMID- 27484451
TI - Wtip is required for proepicardial organ specification and cardiac left/right
asymmetry in zebrafish.
AB - Wilm's tumor 1 interacting protein (Wtip) was identified as an interacting
partner of Wilm's tumor protein (WT1) in a yeast two-hybrid screen. WT1 is
expressed in the proepicardial organ (PE) of the heart, and mouse and zebrafish
wt1 knockout models appear to lack the PE. Wtip's role in the heart remains
unexplored. In the present study, we demonstrate that wtip expression is
identical in wt1a-, tcf21-, and tbx18-positive PE cells, and that Wtip protein
localizes to the basal body of PE cells. We present the first genetic evidence
that Wtip signaling in conjunction with WT1 is essential for PE specification in
the zebrafish heart. By overexpressing wtip mRNA, we observed ectopic expression
of PE markers in the cardiac and pharyngeal arch regions. Furthermore, wtip
knockdown embryos showed perturbed cardiac looping and lacked the
atrioventricular (AV) boundary. However, the chamber-specific markers amhc and
vmhc were unaffected. Interestingly, knockdown of wtip disrupts early left-right
(LR) asymmetry. Our studies uncover new roles for Wtip regulating PE cell
specification and early LR asymmetry, and suggest that the PE may exert non
autonomous effects on heart looping and AV morphogenesis. The presence of cilia
in the PE, and localization of Wtip in the basal body of ciliated cells, raises
the possibility of cilia-mediated PE signaling in the embryonic heart.
PMID- 27484453
TI - MANAGEMENT OF ENDOCRINE DISEASE: The effect of vitamin D supplementation on
glycaemic control in patients with type 2 diabetes mellitus: a systematic review
and meta-analysis.
AB - OBJECTIVE: Epidemiologic studies suggest that vitamin D status plays a role in
glycaemic control in patients with type 2 diabetes. However, intervention studies
yielded inconsistent results. The aim of this study is to systematically review
the effect of vitamin D supplementation on glycaemic control in patients with
type 2 diabetes. METHODS: Systematic review and meta-analysis. We searched
Medline, Embase and the Cochrane Library for RCTs examining the effect of vitamin
D supplementation on glycaemic control in patients with type 2 diabetes. A random
effects model meta-analysis was performed to obtain a summarized outcome of
vitamin D supplementation on HbA1c, fasting glucose and homeostasis model
assessment - insulin resistance (HOMA-IR). RESULTS: Twenty-three RCTs were
included in this systematic review representing a total of 1797 patients with
type 2 diabetes. Mean (+/- s.d.) change in serum 25-hydroxyvitamin D varied from
1.8 +/- 10.2 nmol/L to 80.1 +/- 54.0 nmol/L. Nineteen studies included HbA1c as
outcome variable. Combining these studies no significant effect in change of
HbA1c was seen after vitamin D intervention compared with placebo. A significant
effect of vitamin D supplementation was seen on fasting glucose in a subgroup of
studies (n = 4) with a mean baseline HbA1c >= 8% (64 mmol/mol) (standardized
difference in means: 0.36; 95% CI: 0.12-0.61, P = 0.003). CONCLUSIONS: Current
evidence of RCTs does not support short-term vitamin D supplementation in a
heterogeneous population with type 2 diabetes. However, in patients with poorly
controlled diabetes, a favourable effect of vitamin D is seen on fasting glucose.
PMID- 27484452
TI - A brief history of the search for the protein(s) involved in the acute regulation
of steroidogenesis.
AB - The synthesis of steroid hormones occurs in specific cells and tissues in the
body in response to trophic hormones and other signals. In order to synthesize
steroids de novo, cholesterol, the precursor of all steroid hormones, must be
mobilized from cellular stores to the inner mitochondrial membrane (IMM) to be
converted into the first steroid formed, pregnenolone. This delivery of
cholesterol to the IMM is the rate-limiting step in this process, and has long
been known to require the rapid synthesis of a new protein(s) in response to
stimulation. Although several possibilities for this protein have arisen over the
past few decades, most of the recent attention to fill this role has centered on
the candidacies of the proteins the Translocator Protein (TSPO) and the
Steroidogenic Acute Regulatory Protein (StAR). In this review, the process of
regulating steroidogenesis is briefly described, the characteristics of the
candidate proteins and the data supporting their candidacies summarized, and some
recent findings that propose a serious challenge for the role of TSPO in this
process are discussed.
PMID- 27484454
TI - MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia:
mechanisms, implications and treatment.
AB - BACKGROUND: Patients with moderate to severe hypothyroidism and mainly patients
with myxedema may exhibit reduced sodium levels (<135 mmol/L). SUMMARY: The aim
of this short review is the presentation of the mechanisms of hyponatremia and of
the available data regarding its implications and treatment in patients with
hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid
stimulating hormone determination is mandatory during the evaluation of patients
with reduced serum sodium levels. The main mechanism for the development of
hyponatremia in patients with chronic hypothyroidism is the decreased capacity of
free water excretion due to elevated antidiuretic hormone levels, which are
mainly attributed to the hypothyroidism-induced decrease in cardiac output.
However, recent data suggest that the hypothyroidism-induced hyponatremia is
rather rare and probably occurs only in severe hypothyroidism and myxedema. Other
possible causes and superimposed factors of hyponatremia (e.g. drugs, infections,
adrenal insufficiency) should be considered in patients with mild/moderate
hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually
adequate for the management of mild hyponatremia in patients with hypothyroidism.
Patients with possible hyponatremic encephalopathy should be urgently treated
according to current guidelines. CONCLUSIONS: Severe hypothyroidism may be the
cause of hyponatremia. All hypothyroid patients with low serum sodium levels
should be evaluated for other causes and superimposed factors of hyponatremia and
treated accordingly.
PMID- 27484455
TI - Application of Roof-Shape Amines as Chiral Solvating Agents for Discrimination of
Optically Active Acids by NMR Spectroscopy: Study of Match-Mismatch Effect and
Crystal Structure of the Diastereomeric Salts.
AB - Optically active roof-shape amines were prepared and scanned as chiral solvating
agents to study molecular recognition of acids by NMR analysis. Three types of
amines were studied to establish a match-mismatch effect for structurally diverse
acid analytes. Single-crystal X-ray diffraction analysis was performed on the
diastereomeric salts of roof-shape amines and both isomers of mandelic acid to
establish molecular conformation and correlate the absolute configuration with
the observed NMR shift. The present system also recognizes the two isomers of
weakly acidic BINOL and its derivatives.
PMID- 27484456
TI - Transcranial direct current stimulation in post-stroke sub-acute aphasia: study
protocol for a randomized controlled trial.
AB - BACKGROUND: Transcranial direct current stimulation (tDCS) is a promising new
technique to optimize the effect of regular Speech and Language Therapy (SLT) in
the context of aphasia rehabilitation. The present study focuses on the effect of
tDCS provided during SLT in the sub-acute stage after stroke. The primary aim is
to evaluate the potential effect of tDCS on language functioning, specifically on
word-finding, as well as generalization effects to verbal communication. The
secondary aim is to evaluate its effect on social participation and quality of
life, and its cost-effectiveness. METHODS: We strive to include 58 stroke
patients with aphasia, enrolled in an inpatient or outpatient stroke
rehabilitation program, in a multicenter, double-blind, randomized controlled
trial with two parallel groups and 6 months' follow-up. Patients will participate
in two separate intervention weeks, with a pause of 2 weeks in between, in the
context of their regular aphasia rehabilitation program. The two intervention
weeks comprise daily 45-minute sessions of word-finding therapy, combined with
either anodal tDCS over the left inferior frontal gyrus (1 mA, 20 minutes;
experimental condition) or sham-tDCS over the same region (control condition).
The primary outcome measure is word-finding. Secondary outcome measures are
verbal communication, social participation, quality of life, and cost
effectiveness of the intervention. DISCUSSION: Our results will contribute to the
discussion on whether tDCS should be implemented in regular aphasia
rehabilitation programs for the sub-acute post-stroke population in terms of
(cost-)effectiveness. TRIAL REGISTRATION: Nederlands Trail Register: NTR4364 .
Registered on 21 February 2014.
PMID- 27484457
TI - Development and validation of the Self-Regulation of Eating Behaviour
Questionnaire for adults.
AB - BACKGROUND: Eating self-regulatory capacity can help individuals to cope with the
obesogenic environment and achieve, as well as maintain, a healthy weight and
diet. At present, there is no comprehensive, reliable and valid questionnaire for
assessing this capacity and measuring change in response to self-regulation
interventions in adults. This paper reports the development of the Self
regulation of Eating Behaviour Questionnaire (SREBQ) for use in UK adults, and
presents evidence for its reliability and construct validity. The development of
the SREBQ involved generation of an item pool, followed by two pilot studies
(Samples 1 and 2) and a test of the questionnaire's underlying factor structure
(Sample 3). The final version of the SREBQ was then assessed for reliability and
construct validity (Sample 4). RESULTS: Development of the SREBQ resulted in a 5
item questionnaire. The face validity was satisfactory, as assessed by the pilot
studies. The factor structure analysis (Sample 3) suggested that it has a single
underlying factor, which was confirmed in a second sample (Sample 4). The SREBQ
had strong construct validity, showing a positive correlation with general
measures of self-regulation. It was also positively correlated with motivation
and behavioural automaticity, and negatively correlated with food responsiveness
and emotional over-eating (p < 0.001). It showed good discriminant validity, as
it was only weakly associated with satiety responsiveness, food fussiness and
slowness in eating. CONCLUSIONS: The SREBQ is a reliable and valid measure for
assessment of eating self-regulatory capacity in the general UK adult population.
PMID- 27484459
TI - A biologically-assisted curved muscle model of the lumbar spine: Model
validation.
AB - BACKGROUND: Biomechanical models have been developed to predict spinal loads in
vivo to assess potential risk of injury in workplaces. Most models represent
trunk muscles with straight-lines. Even though straight-line muscles behave
reasonably well in simple exertions, they could be less reliable during complex
dynamic exertions. A curved muscle representation was developed to overcome this
issue. However, most curved muscle models have not been validated during dynamic
exertions. Thus, the objective of this study was to investigate the fidelity of a
curved muscle model during complex dynamic lifting tasks, and to investigate the
changes in spine tissue loads. METHODS: Twelve subjects (7 males and 5 females)
participated in this study. Subjects performed lifting tasks as a function of
load weight, load origin, and load height to simulate complex exertions. Moment
matching measures were recorded to evaluate how well the model predicted spinal
moments compared to measured spinal moments from T12/L1 to L5/S1 levels.
FINDINGS: The biologically-assisted curved muscle model demonstrated better model
performance than the straight-line muscle model between various experimental
conditions. In general, the curved muscle model predicted at least 80% of the
variability in spinal moments, and less than 15% of average absolute error across
levels. The model predicted that the compression and anterior-posterior shear
load significantly increased as trunk flexion increased, whereas the lateral
shear load significantly increased as trunk twisted more asymmetric during
lifting tasks. INTERPRETATION: A curved muscle representation in a biologically
assisted model is an empirically reasonable approach to accurately predict spinal
moments and spinal tissue loads of the lumbar spine.
PMID- 27484458
TI - Dreaming under anesthesia: is it a real possiblity? Investigation of the effect
of preoperative imagination on the quality of postoperative dream recalls.
AB - BACKGROUND: Images evoked immediately before the induction of anesthesia by means
of suggestions may influence dreaming during anesthesia. This study is a
retrospective re-evaluation of the original prospective randomized trial.
METHODS: Dream reports were studied in two groups. In group 1. dreams of patients
who received suggestions, and in group 2, those of the control group of patients
who did not. The incidence of dream reports and the characteristics and the theme
of the reported dreams were compared among the groups. RESULTS: In general, the
control and the psychological intervention groups were different in terms of
dreaming frequency, and non-recall dreaming. The incidence of dream reports was
significantly higher in the suggestion group (82/190 at 10 min and 71/190 at 60
min respectively) than in the control group (16/80 at 10 min and 13/80 at 60 min,
respectively; p10 = 0.001 and p60 = 0.002). There were no differences in the
nature (thought- like or cinematic), quality (color or B&W) and the mood
(positive vs. negative) of the recalled dreams. In general, the contents of the
imaginary favorite place and the reported dream were identical in 73.2 %. Among
the topics most successfully applied in the operating theater were loved ones
(83.8 %), holiday (77.8 %) and sport (63.6 %). CONCLUSION: The results of the
present study suggest that dreams during anesthesia are influenced by suggestions
administered immediately preceding anesthesia. TRIAL REGISTRATION: The study was
registered in ClinicalTrials.gov. Identifier: Q1 NCT01839201 , Date: 12 Apr.
2013.
PMID- 27484460
TI - Preferred SLA class I/class II haplotype combinations in German Landrace pigs.
AB - Major histocompatibility complex (MHC) molecules are responsible for the antigen
presentation to T lymphocytes. High recombination rates in the MHC genes, as
observed in humans, are believed to serve the evolutionary goal to achieve a high
genetic diversity, allowing for a broad and efficient immune response. In a
cohort of 155 pedigreed German Landrace pigs (65 founders and 90 piglets), we
found that MHC genes occur in particular class I and class II haplotype
combinations. This phenomenon has not been described before, probably because
most of the earlier MHC studies in pigs were not pedigree-based. After comparing
our data with published genotypes of different European pig breeds and Asian
pigs, we hypothesise that the combination of particular but different haplotypes
in different geographical regions may have developed under the evolutionary
pressure of regionally endemic pathogens. This proposed mechanism ensures an
efficient immune response despite low recombination rates.
PMID- 27484462
TI - Shell Biorefinery: Dream or Reality?
AB - Shell biorefinery, referring to the fractionation of crustacean shells into their
major components and the transformation of each component into value-added
chemicals and materials, has attracted growing attention in recent years. Since
the large quantities of waste shells remain underexploited, their valorization
can potentially bring both ecological and economic benefits. This Review provides
an overview of the current status of shell biorefinery. It first describes the
structural features of crustacean shells, including their composition and their
interactions. Then, various fractionation methods for the shells are introduced.
The last section is dedicated to the valorization of chitin and its derivatives
for chemicals, porous carbon materials and functional polymers.
PMID- 27484461
TI - Construction and internal validation of a new mortality risk score for patients
admitted to the intensive care unit.
AB - BACKGROUND: The existing models to predict mortality in intensive care units
(ICU) present difficulties in clinical practice. OBJECTIVES: The aim of this
study was to develop and internally validate a points system to predict mortality
in the ICU, which can be applied instantly and with high discriminating power.
METHODS: This cohort study comprised all patients admitted to the ICU in a
Spanish region between January 2013 and April 2014, followed from admission to
death or discharge (N=1113). Primary variable: ICU mortality. Secondary variables
at admission: gender, Fried criteria for frailty, function scale, medical
admission, cardiac arrest, cardiology admission, sepsis, mechanical ventilation,
inotropic support, age, frailty index and clinical frailty scale. The sample was
divided randomly into two groups (80% and 20%): construction (n=844) and internal
validation (n=269). Construction: A logistic regression model was implemented and
adapted to the points system. VALIDATION: the area under the ROC curve (AUC) of
the model was calculated and the risk quintiles were created to determine whether
differences existed between observed and expected deaths. RESULTS: The points
system included: function scale, medical admission, cardiology admission, sepsis,
mechanical ventilation and inotropic support. The validation showed: (i) AUC=0.95
(95% CI: 0.91-0.99, p<.001); (ii) No differences between observed and expected
deaths (p=.799). CONCLUSIONS: A predictive model of mortality in the ICU has been
constructed and internally validated. This model improves on the previous models
through its simplicity, its discriminating power and free use. External
validation studies are needed in other geographical areas.
PMID- 27484463
TI - Clinical significance of the oral corticosteroid reversibility test in asthma
with fixed airflow obstruction.
PMID- 27484464
TI - Missed Opportunity: Why Parents Refuse Influenza Vaccination for Their
Hospitalized Children.
AB - BACKGROUND AND OBJECTIVES: Hospitals are required to screen and administer the
influenza vaccine to all admitted children unless contraindicated or refused by
parents, yet vaccination rates remain low. Our goal was to examine reasons for
refusal among pediatric patients admitted during influenza season. METHODS: All
children age 6 months to 18 years admitted to 2 network community hospitals from
October 1, 2013 to March 31, 2014, without contraindications, were offered
influenza vaccination prior to discharge. Parents who refused vaccination were
asked their reason for refusal. Chi-square tests and logistic regression were
used to determine factors associated with refusing the vaccine in the inpatient
setting. RESULTS: Three hundred twenty-five of 786 unique patients admitted
during influenza season were eligible for vaccination. Of these, 49.8% refused.
Parents of females, whites, and those with private insurance were more likely to
refuse vaccination. Patients whose immunization status was otherwise up to date
were more likely to accept (Odds Ratio 2.39, 95% Confidence Interval 1.05-5.41).
Commonly cited reasons for refusal were: preference to have vaccination by the
primary care provider (24.1%), concern for side effects (16.1%), not wanting
vaccination (13%), doubt in efficacy (8%), concern that the child was already
sick (6.8%), no prior influenza vaccination (6.7%) and feeling that it was not
needed (5.6%). CONCLUSIONS: Hospitalization during influenza season provides an
opportunity for health-care providers to educate families about influenza and
vaccinate patients if appropriate. However, nearly half of parents of eligible
children declined vaccination. More study is required to determine strategies
that can increase influenza vaccination acceptance.
PMID- 27484465
TI - Types of health care facilities and the quality of primary care: a study of
characteristics and experiences of Chinese patients in Guangdong Province, China.
AB - BACKGROUND: In China, most people tend to use hospitals rather than health
centers for their primary care generally due to the perception that quality of
care provided in the hospital setting is superior to that provided at the health
centers. No studies have been conducted in China to compare the quality of
primary care provided at different health care settings. The purpose of this
study is to compare the quality of primary care provided in different types of
health care facilities in China. METHODS: A cross-sectional survey with patients
was conducted in Guangdong province of China, using the validated Chinese Primary
Care Assessment Tool (PCAT). ANOVA was performed to compare the overall and 10
domains of primary care quality for patients in tertiary, secondary, and primary
health care settings. Multivariate analyses were used to assess the association
between types of facility and quality of primary care attributes while
controlling for sociodemographic and health care characteristics. RESULTS: The
final number of respondents was 864 including 161 from county hospitals, 190 from
rural community health centers (CHCs), 164 from tertiary hospitals, 80 from
secondary hospitals, and 269 from urban CHCs. Type of health care facilities was
significantly associated with total PCAT score and domain scores. CHC was
associated with higher total PCAT score and scores for first contact-access,
ongoing care, comprehensiveness-services available, and community orientation
than secondary and/or tertiary hospitals, after controlling for patients'
demographic and health characteristics. Higher PCAT score was associated with
greater satisfaction with primary care received. CHC patients were more likely to
report satisfactory experiences compared to patients from secondary and tertiary
facilities. CONCLUSIONS: The study demonstrated that CHCs provided better quality
primary care when compared with secondary and tertiary health care facilities,
justifying CHCs as a model of primary care delivery.
PMID- 27484467
TI - Inflammatory bowel disease mimicking granulomatosis with polyangiitis: a case
report.
AB - BACKGROUND: We report a case in which the extraintestinal manifestations of
inflammatory bowel disease preceded development of gastrointestinal symptoms by
nearly 9 months in the context of an unusual autoantibody panel, mimicking
granulomatosis with polyangiitis. This case highlights the intricacies and
overlap of autoimmune diseases, and illustrates an interesting clinical
phenotype: cytoplasmic anti-neutrophil cytoplasmic antibody positive inflammatory
bowel disease with predominantly extraintestinal manifestations. Perinuclear anti
neutrophil cytoplasmic antibody positivity has been frequently reported in
association with inflammatory bowel disease, but cytoplasmic anti-neutrophil
cytoplasmic antibody positivity is uncommon. CASE PRESENTATION: A 54-year-old
African-American man presented to our internal medicine resident clinic at the
Johns Hopkins Hospital with several months of systemic inflammatory features:
anterior uveitis, auricular chondritis, monoarthritis, fever, and weight loss. He
did not have a primary care physician due to lack of health insurance and had
been seen in our emergency department several times over the past year. These
features fit nicely with a diagnosis of granulomatosis with polyangiitis,
especially given positive cytoplasmic anti-neutrophil cytoplasmic antibodies.
However, 9 months into his clinical course he developed hematochezia with
perirectal abscess and fistula. A colonoscopy with biopsy confirmed a diagnosis
of inflammatory bowel disease. CONCLUSIONS: This case highlights the fact that
extraintestinal manifestations may precede gastrointestinal symptoms of
inflammatory bowel disease for months, which may delay diagnosis if not
understood and recognized. It further highlights an interesting disease phenotype
that has not been widely reported, but may deserve further study. Lastly, the
case stresses the importance of the internist in identifying a unifying diagnosis
in a slowly evolving clinical process with the assistance of subspecialists. In
this respect, the case is of interest to general internists, as well as
rheumatologists and gastroenterologists.
PMID- 27484466
TI - Inhibition of nuclear factor-kappa B enhances the tumor growth of ovarian cancer
cell line derived from a low-grade papillary serous carcinoma in p53-independent
pathway.
AB - BACKGROUND: NF-kB can function as an oncogene or tumor suppressor depending on
cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has
never been tested. We sought to elucidate the function of NF-kB in the low-grade
serous ovarian cancer. METHODS: The ovarian cancer cell line, HOC-7, derived from
a low-grade papillary serous carcinoma. Introduction of a dominant negative
mutant, IkBalphaM, which resulted in decrease of NF-kB function in ovarian cancer
cell lines. The transcription ability, tumorigenesis, cell proliferation and
apoptosis were observed in derivative cell lines in comparison with parental
cells. RESULTS: Western blot analysis indicated increased expression of the anti
apoptotic proteins Bcl-xL and reduced expression of the pro-apoptotic proteins
Bax, Bad, and Bid in HOC-7/IKBalphaM cell. Further investigations validate this
conclusion in KRAS wildtype cell line SKOV3. Interesting, NF-kB can exert its pro
apoptotic effect by activating mitogen-activated protein kinase (MAPK)
phosphorylation in SKOV3 ovarian cancer cell, whereas opposite changes detected
in p-MEK in HOC-7 ovarian cancer cell, the same as some chemoresistant ovarian
cancer cell lines. In vivo animal assay performed on BALB/athymic mice showed
that injection of HOC-7 induced subcutaneous tumor growth, which was completely
regressed within 7 weeks. In comparison, HOC-7/IKBalphaM cells caused sustained
tumor growth and abrogated tumor regression, suggesting that knock-down of NF-kB
by IKBalphaM promoted sustained tumor growth and delayed tumor regression in HOC
7 cells. CONCLUSION: Our results demonstrated that NF-kB may function as a tumor
suppressor by facilitating regression of low grade ovarian serous carcinoma
through activating pro-apoptotic pathways.
PMID- 27484468
TI - Can policy ameliorate socioeconomic inequities in obesity and obesity-related
behaviours? A systematic review of the impact of universal policies on adults and
children.
AB - This systematic review examined the impact of universal policies on socioeconomic
inequities in obesity, dietary and physical activity behaviours among adults and
children. PRISMA-Equity guidelines were followed. Database searches spanned from
2004 to August 2015. Eligible studies assessed the impact of universal policies
on anthropometric, dietary or physical activity-related outcomes in adults or
children according to socioeconomic position. Thirty-six studies were included.
Policies were classified as agentic, agento-structural or structural, and their
impact on inequities was rated as positive, neutral, negative or mixed according
to the dominant associations observed. Most policies had neutral impacts on
obesity-related inequities regardless of whether they were agentic (60% neutral),
agento-structural (68% neutral) or structural (67% neutral). The proportion of
positive impacts was similar across policy types (10% agentic, 18% agento
structural and 11% structural), with some differences for negative impacts (30%
agentic, 14% agento-structural and 22% structural). The majority of associations
remained neutral when stratified by participant population, implementation level
and socioeconomic position measures and by anthropometric and behavioural
outcomes. Fiscal measures had consistently neutral or positive impacts on
inequities. Findings suggest an important role for policy in addressing obesity
in an equitable manner and strengthen the case for implementing a broad
complement of policies spanning the agency-structure continuum.
PMID- 27484469
TI - Comparison of glycosaminoglycan chemical exchange saturation transfer using
Gaussian-shaped and off-resonant spin-lock radiofrequency pulses in
intervertebral disks.
AB - PURPOSE: To investigate, if a train of spin-lock pulses (chemical exchange
saturation transfer with spin-lock pulses = CESL) improves biochemical
glycosaminoglycan imaging compared with conventional chemical exchange saturation
transfer with Gaussian-shaped pulses (CEST) in lumbar intervertebral discs.
METHODS: T2 , CEST, and CESL imaging was performed in lumbar intervertebral discs
of 15 healthy volunteers at 3 Tesla. Mean and standard deviation of the
asymmetric magnetization transfer ratio (MTRasym ), the asymmetric spin-lock
ratio (SLRasym ) and T2 values were calculated for nucleus pulposus (NP) and
annulus fibrosus (AF). Wilcoxon test was used to analyze differences between
MTRasym and SLRasym . Pearson correlation was used to determine the relationship
between MTRasym , SLRasym and T2 . RESULTS: Data showed no significant difference
between MTRasym and SLRasym (NP: P = 0.35; AF: P = 0.34). MTRasym and SLRasym
values differed significantly between NP and AF (MTRasym : P = 0.014, SLRasym : P
= 0.005). T2 values correlated significantly with MTRasym (NP: rho = 0.76, P <
0.001; AF: rho = 0.60, P < 0.001) and SLRasym (NP: rho = 0.73, P < 0.001; AF: rho
= 0.47, P < 0.001). CONCLUSION: CESL does not improve the chemical exchange
asymmetry effect compared with conventional CEST, but leads to comparable
results. Magn Reson Med 78:280-284, 2017. (c) 2016 International Society for
Magnetic Resonance in Medicine.
PMID- 27484471
TI - Exploring the Nutrition and Health Claims Regulation (EC) No. 1924/2006: What is
the impact on innovation in the EU food sector?
AB - Literature suggests that despite its positive aim of promoting innovation, the
Nutrition and Health Claims Regulation (EC) No. 1924/2006 (NHCR) may bring along
several compliance challenges, which might affect innovation in the EU food
sector. This study investigates the challenges faced by companies to comply with
the NHCR (specifically Article 13.1) and their impact on innovation. To this end,
we conducted an online survey with 105 companies involved in the EU food sector.
Results indicate that companies perceive wording of claims, missing transparency
and limited financial resources as major challenges to comply with the NHCR
(Article 13.1). Companies reported not to have increased their R&D expenditure or
innovation activities after the NHCR (Article 13.1) was implemented. Thus, this
study highlights specific compliance challenges related to the NHCR (Article
13.1) and indicates that currently, the regulation does not seem to have fostered
innovation in the EU food sector.
PMID- 27484470
TI - Physical activity, body mass index and heart rate variability-based stress and
recovery in 16 275 Finnish employees: a cross-sectional study.
AB - BACKGROUND: Physical inactivity, overweight, and work-related stress are major
concerns today. Psychological stress causes physiological responses such as
reduced heart rate variability (HRV), owing to attenuated parasympathetic and/or
increased sympathetic activity in cardiac autonomic control. This study's purpose
was to investigate the relationships between physical activity (PA), body mass
index (BMI), and HRV-based stress and recovery on workdays, among Finnish
employees. METHODS: The participants in this cross-sectional study were 16 275
individuals (6863 men and 9412 women; age 18-65 years; BMI 18.5-40.0 kg/m(2)).
Assessments of stress, recovery and PA were based on HRV data from beat-to-beat R
R interval recording (mainly over 3 days). The validated HRV-derived variables
took into account the dynamics and individuality of HRV. Stress percentage (the
proportion of stress reactions, workday and working hours), and stress balance
(ratio between recovery and stress reactions, sleep) describe the amount of
physiological stress and recovery, respectively. Variables describing the
intensity (i.e. magnitude of recognized reactions) of physiological stress and
recovery were stress index (workday) and recovery index (sleep), respectively.
Moderate to vigorous PA was measured and participants divided into the following
groups, based on calculated weekly PA: inactive (0 min), low (0 < 150 min),
medium (150-300 min), and high (>300 min). BMI was calculated from self-reported
weight and height. Linear models were employed in the main analyses. RESULTS:
High PA was associated with lower stress percentages (during workdays and working
hours) and stress balance. Higher BMI was associated with higher stress index,
and lower stress balance and recovery index. These results were similar for men
and women (P < 0.001 for all). CONCLUSION: Independent of age and sex, high PA
was associated with a lower amount of stress on workdays. Additionally, lower BMI
was associated with better recovery during sleep, expressed by a greater amount
and magnitude of recovery reactions, which suggests that PA in the long term
resulting in improved fitness has a positive effect on recovery, even though high
PA may disturb recovery during the following night. Obviously, several factors
outside of the study could also affect HRV-based stress.
PMID- 27484472
TI - Outcomes following emergent open repair for thoracic aortic dissection are
improved at higher volume centers in direct admissions and transfers.
AB - BACKGROUND: The purpose of this study is (1) to define the proportion of patients
undergoing emergent open repair of thoracic aortic dissection admitted directly
through the emergency room versus those transferred from outside hospitals and
(2) to determine if a volume-outcomes relationship exists for those patients
across admission types. METHODS: De-identified patient-level data was obtained
from the Nationwide Inpatient Sample (2004-2008). Patients undergoing emergent
aortic surgery for thoracic aortic dissection (n = 1,507) were identified by ICD
9 codes and stratified by annual center volume into low volume (<=5 cases/year)
(n = 963; 63.9 %), intermediate volume (6-10 cases/year) (n = 370; 24.5 %), and
high volume (>=11 cases/year) (n = 174; 11.6 %) groups. The analysis was further
stratified by admission type: direct admission (DA), transfer admission (TA), and
other. The primary outcome was in-hospital mortality. Multivariate logistic
regression analysis was performed comparing outcomes between high vs low and high
vs intermediate volume centers. RESULTS: Overall in-hospital mortality was 21.8 %
(n = 328/1,507). Absolute percent mortality at high volume centers was
significantly lower (12.6 %) than at medium (20.6 %) and low volume (23.9 %)
centers. For DA patients, mortality was 10.6, 21.4, and 24.0 % for high, medium,
and low volume centers respectively. For TA patients, mortality was 10.2, 12.7,
and 23.5 % for high, medium, and low volume centers, respectively. Multivariate
analysis suggested that patients in low volume center were more likely to die
compared to high volume center (Odds Ratio 2.06, 95 % CI 1.25 - 3.38, p = 0.004).
Admission source was not associated with increased mortality. CONCLUSIONS: Direct
admissions comprise the largest proportion of dissections regardless of volume
strata, and they comprise the largest proportion in the low and intermediate
volume cohorts. Admission to low volume center is an independent risk factor for
increased mortality. Patients transferred to high volume centers from low volume
centers have similar outcome as direct admits in terms of mortality.
PMID- 27484473
TI - Effect of magnesium ions on the structure of DNA thin films: an infrared
spectroscopy study.
AB - Utilizing Fourier transform infrared spectroscopy we have investigated the
vibrational spectrum of thin dsDNA films in order to track the structural changes
upon addition of magnesium ions. In the range of low magnesium concentration
([magnesium]/[phosphate] = [Mg]/[P] < 0.5), both the red shift and the intensity
of asymmetric PO2 stretching band decrease, indicating an increase of magnesium
phosphate binding in the backbone region. Vibration characteristics of the A
conformation of the dsDNA vanish, whereas those characterizing the B conformation
become fully stabilized. In the crossover range with comparable Mg and intrinsic
Na DNA ions ([Mg]/[P] ~ 1) B conformation remains stable; vibrational spectra
show moderate intensity changes and a prominent blue shift, indicating a
reinforcement of the bonds and binding in both the phosphate and the base
regions. The obtained results reflect the modified screening and local charge
neutralization of the dsDNA backbone charge, thus consistently demonstrating that
the added Mg ions interact with DNA via long-range electrostatic forces. At high
Mg contents ([Mg]/[P] > 10), the vibrational spectra broaden and show a striking
intensity rise, while the base stacking remains unaffected. We argue that at
these extreme conditions, where a charge compensation by vicinal counterions
reaches 92-94%, DNA may undergo a structural transition into a more compact form.
PMID- 27484474
TI - Differential peak calling of ChIP-seq signals with replicates with THOR.
AB - The study of changes in protein-DNA interactions measured by ChIP-seq on dynamic
systems, such as cell differentiation, response to treatments or the comparison
of healthy and diseased individuals, is still an open challenge. There are few
computational methods comparing changes in ChIP-seq signals with replicates.
Moreover, none of these previous approaches addresses ChIP-seq specific
experimental artefacts arising from studies with biological replicates. We
propose THOR, a Hidden Markov Model based approach, to detect differential peaks
between pairs of biological conditions with replicates. THOR provides all pre-
and post-processing steps required in ChIP-seq analyses. Moreover, we propose a
novel normalization approach based on housekeeping genes to deal with cases where
replicates have distinct signal-to-noise ratios. To evaluate differential peak
calling methods, we delineate a methodology using both biological and simulated
data. This includes an evaluation procedure that associates differential peaks
with changes in gene expression as well as histone modifications close to these
peaks. We evaluate THOR and seven competing methods on data sets with distinct
characteristics from in vitro studies with technical replicates to clinical
studies of cancer patients. Our evaluation analysis comprises of 13 comparisons
between pairs of biological conditions. We show that THOR performs best in all
scenarios.
PMID- 27484475
TI - YphC and YsxC GTPases assist the maturation of the central protuberance, GTPase
associated region and functional core of the 50S ribosomal subunit.
AB - YphC and YsxC are GTPases in Bacillus subtilis that facilitate the assembly of
the 50S ribosomal subunit, however their roles in this process are still
uncharacterized. To explore their function, we used strains in which the only
copy of the yphC or ysxC genes were under the control of an inducible promoter.
Under depletion conditions, they accumulated incomplete ribosomal subunits that
we named 45SYphC and 44.5SYsxC particles. Quantitative mass spectrometry analysis
and the 5-6 A resolution cryo-EM maps of the 45SYphC and 44.5SYsxC particles
revealed that the two GTPases participate in the maturation of the central
protuberance, GTPase associated region and key RNA helices in the A, P and E
functional sites of the 50S subunit. We observed that YphC and YsxC bind
specifically to the two immature particles, suggesting that they represent either
on-pathway intermediates or that their structure has not significantly diverged
from that of the actual substrate. These results describe the nature of these
immature particles, a widely used tool to study the assembly process of the
ribosome. They also provide the first insights into the function of YphC and YsxC
in 50S subunit assembly and are consistent with this process occurring through
multiple parallel pathways, as it has been described for the 30S subunit.
PMID- 27484476
TI - Origins of tmRNA: the missing link in the birth of protein synthesis?
AB - The RNA world hypothesis refers to the early period on earth in which RNA was
central in assuring both genetic continuity and catalysis. The end of this era
coincided with the development of the genetic code and protein synthesis,
symbolized by the apparition of the first non-random messenger RNA (mRNA). Modern
transfer-messenger RNA (tmRNA) is a unique hybrid molecule which has the
properties of both mRNA and transfer RNA (tRNA). It acts as a key molecule during
trans-translation, a major quality control pathway of modern bacterial protein
synthesis. tmRNA shares many common characteristics with ancestral RNA. Here, we
present a model in which proto-tmRNAs were the first molecules on earth to
support non-random protein synthesis, explaining the emergence of early genetic
code. In this way, proto-tmRNA could be the missing link between the first mRNA
and tRNA molecules and modern ribosome-mediated protein synthesis.
PMID- 27484477
TI - Identification of distinct biological functions for four 3'-5' RNA polymerases.
AB - The superfamily of 3'-5' polymerases synthesize RNA in the opposite direction to
all other DNA/RNA polymerases, and its members include eukaryotic tRNA(His)
guanylyltransferase (Thg1), as well as Thg1-like proteins (TLPs) of unknown
function that are broadly distributed, with family members in all three domains
of life. Dictyostelium discoideum encodes one Thg1 and three TLPs (DdiTLP2,
DdiTLP3 and DdiTLP4). Here, we demonstrate that depletion of each of the genes
results in a significant growth defect, and that each protein catalyzes a unique
biological reaction, taking advantage of specialized biochemical properties.
DdiTLP2 catalyzes a mitochondria-specific tRNA(His) maturation reaction, which is
distinct from the tRNA(His) maturation reaction typically catalyzed by Thg1
enzymes on cytosolic tRNA. DdiTLP3 catalyzes tRNA repair during mitochondrial
tRNA 5'-editing in vivo and in vitro, establishing template-dependent 3'-5'
polymerase activity of TLPs as a bona fide biological activity for the first time
since its unexpected discovery more than a decade ago. DdiTLP4 is cytosolic and,
surprisingly, catalyzes robust 3'-5' polymerase activity on non-tRNA substrates,
strongly implying further roles for TLP 3'-5' polymerases in eukaryotes.
PMID- 27484478
TI - Meiotic prophase roles of Rec8 in crossover recombination and chromosome
structure.
AB - Rec8 is a prominent component of the meiotic prophase chromosome axis that
mediates sister chromatid cohesion, homologous recombination and chromosome
synapsis. Here, we explore the prophase roles of Rec8. (i) During the meiotic
divisions, Rec8 phosphorylation mediates its separase-mediated cleavage. We show
here that such cleavage plays no detectable role for chromosomal events of
prophase. (ii) We have analyzed in detail three rec8 phospho-mutants, with 6, 24
or 29 alanine substitutions. A distinct 'separation of function' phenotype is
revealed. In the mutants, axis formation and recombination initiation are normal,
as is non-crossover recombination; in contrast, crossover (CO)-related events are
defective. Moreover, the severities of these defects increase coordinately with
the number of substitution mutations, consistent with the possibility that global
phosphorylation of Rec8 is important for these effects. (iii) We have analyzed
the roles of three kinases that phosphorylate Rec8 during prophase. Timed
inhibition of Dbf4-dependent Cdc7 kinase confers defects concordant with rec8
phospho-mutant phenotypes. Inhibition of Hrr25 or Cdc5/polo-like kinase does not.
Our results suggest that Rec8's prophase function, independently of cohesin
cleavage, contributes to CO-specific events in conjunction with the maintenance
of homolog bias at the leptotene/zygotene transition of meiotic prophase.
PMID- 27484479
TI - Self-assembly of fully addressable DNA nanostructures from double crossover
tiles.
AB - DNA origami and single-stranded tile (SST) are two proven approaches to self
assemble finite-size complex DNA nanostructures. The construction elements
appeared in structures from these two methods can also be found in multi-stranded
DNA tiles such as double crossover tiles. Here we report the design and
observation of four types of finite-size lattices with four different double
crossover tiles, respectively, which, we believe, in terms of both complexity and
robustness, will be rival to DNA origami and SST structures.
PMID- 27484480
TI - Identify bilayer modules via pseudo-3D clustering: applications to miRNA-gene
bilayer networks.
AB - Module identification is a frequently used approach for mining local structures
with more significance in global networks. Recently, a wide variety of bilayer
networks are emerging to characterize the more complex biological processes. In
the light of special topological properties of bilayer networks and the
accompanying challenges, there is yet no effective method aiming at bilayer
module identification to probe the modular organizations from the more inspiring
bilayer networks. To this end, we proposed the pseudo-3D clustering algorithm,
which starts from extracting initial non-hierarchically organized modules and
then iteratively deciphers the hierarchical organization of modules according to
a bottom-up strategy. Specifically, a modularity function for bilayer modules was
proposed to facilitate the algorithm reporting the optimal partition that gives
the most accurate characterization of the bilayer network. Simulation studies
demonstrated its robustness and outperformance against alternative competing
methods. Specific applications to both the soybean and human miRNA-gene bilayer
networks demonstrated that the pseudo-3D clustering algorithm successfully
identified the overlapping, hierarchically organized and highly cohesive bilayer
modules. The analyses on topology, functional and human disease enrichment and
the bilayer subnetwork involved in soybean fat biosynthesis provided both the
theoretical and biological evidence supporting the effectiveness and robustness
of pseudo-3D clustering algorithm.
PMID- 27484481
TI - A multi-step model for facilitated unwinding of the yeast U4/U6 RNA duplex.
AB - The small nuclear RNA (snRNA) components of the spliceosome undergo many
conformational rearrangements during its assembly, catalytic activation and
disassembly. The U4 and U6 snRNAs are incorporated into the spliceosome as a base
paired complex within the U4/U6.U5 small nuclear ribonucleoprotein (tri-snRNP).
U4 and U6 are then unwound in order for U6 to pair with U2 to form the
spliceosome's active site. After splicing, U2/U6 is unwound and U6 annealed to U4
to reassemble the tri-snRNP. U6 rearrangements are crucial for spliceosome
formation but are poorly understood. We have used single-molecule Forster
resonance energy transfer and unwinding assays to identify interactions that
promote U4/U6 unwinding and have studied their impact in yeast. We find that
U4/U6 is efficiently unwound using DNA oligonucleotides by coupling unwinding of
U4/U6 stem II with strand invasion of stem I. Unwinding is stimulated by the U6
telestem, which transiently forms in the intact U4/U6 RNA complex. Stabilization
of the telestem in vivo results in accumulation of U4/U6 di-snRNP and impairs
yeast growth. Our data reveal conserved mechanisms for U4/U6 unwinding and
indicate telestem dynamics are critical for tri-snRNP assembly and stability.
PMID- 27484482
TI - Co-incident insertion enables high efficiency genome engineering in mouse
embryonic stem cells.
AB - CRISPR/Cas9 nucleases have enabled powerful, new genome editing capabilities;
however, the preponderance of non-homologous end joining (NHEJ) mediated repair
events over homology directed repair (HDR) in most cell types limits the ability
to engineer precise changes in mammalian genomes. Here, we increase the
efficiency of isolating precise HDR-mediated events in mouse embryonic stem (ES)
cells by more than 20-fold through the use of co-incidental insertion (COIN) of
independent donor DNA sequences. Analysis of on:off-target frequencies at the
Lef1 gene revealed that bi-allelic insertion of a PGK-Neo cassette occurred more
frequently than expected. Using various selection cassettes targeting multiple
loci, we show that the insertion of a selectable marker at one control site
frequently coincided with an insertion at an unlinked, independently targeted
site, suggesting enrichment of a sub-population of HDR-proficient cells. When
individual cell events were tracked using flow cytometry and fluorescent protein
markers, individual cells frequently performed either a homology-dependent
insertion event or a homology-independent event, but rarely both types of
insertions in a single cell. Thus, when HDR-dependent selection donors are used,
COIN enriches for HDR-proficient cells among heterogeneous cell populations. When
combined with a self-excising selection cassette, COIN provides highly efficient
and scarless genome editing.
PMID- 27484484
TI - Ovarian masses with papillary projections diagnosed and removed during pregnancy:
ultrasound features and histological diagnosis.
AB - OBJECTIVE: To elucidate the ultrasound features that can discriminate between
benign and malignant ovarian cysts with papillary projections but no other solid
component in pregnant women. METHODS: Thirty-four women with an ultrasound
diagnosis of an ovarian cyst with papillary projections but no other solid
component that had been removed surgically during pregnancy were identified from
the databases of four ultrasound units. Some clinical and ultrasound information
was collected prospectively. Missing information was obtained retrospectively
from ultrasound images, ultrasound reports and patient records. Using
prospectively and retrospectively collected data, the ultrasound appearance of
the tumors was described using the terms and definitions of the International
Ovarian Tumor Analysis group. The ultrasound characteristics were compared with
the histological diagnosis. RESULTS: Of the 34 cases included, 19 (56%) lesions
were benign (16 decidualized endometriomas, one cystadenofibroma, one simple
cyst, one struma ovarii), 12 (35%) were borderline tumors and three (9%) were
primary invasive tumors (two immature teratomas, one endometrioid
cystadenocarcinoma). The contour of the cyst papillations was smooth in 79%
(15/19) of benign tumors vs 27% (4/15) of malignant tumors (P = 0.002). The
cystic content showed ground-glass echogenicity in 74% (14/19) of benign tumors
vs 13% (2/15) of malignant tumors (P = 0.0006). All ovarian masses with smooth
papillations and ground-glass content (n = 12) were decidualized endometriomas.
The papillary projections were vascularized and the color score was 3 or 4 in 88%
(14/16) of decidualized endometriomas vs 42% (5/12) of borderline tumors (P =
0.013). CONCLUSIONS: In pregnant women, ovarian cysts with ground-glass
echogenicity and papillations with a smooth contour on ultrasound are most likely
to be decidualized endometriomas. Cysts with anechoic or low-level echogenicity
and papillations with an irregular contour suggest borderline malignancy.
Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27484483
TI - An aromatic-rich loop couples DNA binding and ATP hydrolysis in the PriA DNA
helicase.
AB - Helicases couple ATP hydrolysis to nucleic acid binding and unwinding via
molecular mechanisms that remain poorly defined for most enzyme subfamilies
within the superfamily 2 (SF2) helicase group. A crystal structure of the PriA
SF2 DNA helicase, which governs restart of prematurely terminated replication
processes in bacteria, revealed the presence of an aromatic-rich loop (ARL) on
the presumptive DNA-binding surface of the enzyme. The position and sequence of
the ARL was similar to loops known to couple ATP hydrolysis with DNA binding in a
subset of other SF2 enzymes, however, the roles of the ARL in PriA had not been
investigated. Here, we show that changes within the ARL sequence uncouple PriA
ATPase activity from DNA binding. In vitro protein-DNA crosslinking experiments
define a residue- and nucleotide-specific interaction map for PriA, showing that
the ARL binds replication fork junctions whereas other sites bind the leading or
lagging strands. We propose that DNA binding to the ARL allosterically triggers
ATP hydrolysis in PriA. Additional SF2 helicases with similarly positioned loops
may also couple DNA binding to ATP hydrolysis using related mechanisms.
PMID- 27484485
TI - Enantiomeric separation of new phytoalexin analogs with cyclofructan chiral
stationary phases in normal-phase mode.
AB - For the first time, three different derivatized cyclofructan chiral stationary
phases were used for the direct high-performance liquid chromatographic
enantiomeric separation of 11 new racemic analogs of a natural indole
phytoalexin. This class of compounds is known to have significant
antiproliferative activity and other potentially useful pharmacological
properties. The effect of various experimental factors was investigated to
optimize the separations in the normal-phase mode. It was found that the nature
of polar modifier and additive in the mobile phase have significant impact on the
enantioseparations. Better chiral recognition of analyzed compounds was achieved
on (R)-naphthylethyl carbamate cyclofructan 6 than on isopropyl carbamate
cyclofructan 6 and dimethylphenyl carbamate cyclofructan 7. The thermodynamic
parameters showed that the chiral separation was enthalpy controlled in all
cases.
PMID- 27484486
TI - Facilitators and Barriers to Implementing Transitional Care Managers Within a
Public Health Care System.
AB - Transitional care is crucial to ensure quality of care and safety for elderly
patients. In the context of health care reforms promoting a shift from a hospital
centered approach to a home care approach, transitional care becomes a vital
component and social workers can play an important role in easing transitions.
Most recent studies have focused on the development or improvement of
transitional care intervention models or tools, but few have addressed
implementation issues. In this study, the implementation process of an innovative
intervention aiming to integrate transitional care managers (TCMs) from Health
and Social Services Centres (HSSC) within two Canadian hospitals was evaluated.
Data collection comprised focus groups (n = 8), direct observations, meeting
minutes, activity grids and logbooks. To facilitate the implementation of TCMs,
decisions were made to clearly indicate their involvement in patients' files and
concentrated their efforts on a restricted number of units. Barriers included
confusion about target clientele, inequitable information exchange between
partners, limited powers regarding coordination of care, and organizational
constraints limiting additional measures to improve transitional care. Evaluating
implementation processes is crucial to efficiently identify obstacles and apply
additional implementation strategies to promote the integration of new practices
within the health care system.
PMID- 27484488
TI - Higher Doses of Fish Oil-Based Lipid Emulsions Used to Treat Inadequate Weight
Gain and Rising Triene:Tetraene Ratio in a Severely Malnourished Infant With
Intestinal Failure-Associated Liver Disease.
AB - Fish oil-based lipid emulsions (FOLEs) have been used to treat cholestasis in
children with intestinal failure-associated liver disease (IFALD). When FOLEs are
dosed at 1 g/kg/d, essential fatty acid (EFA) deficiency typically does not
occur. We describe the clinical course of a severely malnourished parenteral
nutrition-dependent infant with IFALD. Baseline EFA panels were normal upon
starting FOLE at 1 g/kg/d. Despite biochemical improvement in IFALD, weight
velocity was below target and biochemical EFA status worsened, even after
correction for other factors affecting weight. The FOLE dose was increased to 1.5
g/kg/d, resulting in improvement of weight velocity and EFA status. This suggests
that in severely malnourished infants being treated for IFALD, higher doses of
FOLE may be required for adequate growth and to prevent EFA deficiency.
PMID- 27484487
TI - Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood
group B antigen: Functionality and stability studies.
AB - Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce
haemagglutination and are used worldwide for diagnostic blood typing. Contrary to
the current belief that IgGs are too small to simultaneously bind antigens on two
different erythrocytes, we obtained agglutinating mouse IgG3 that recognized
antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing
isotype that has the ability to form Fc-dependent oligomers. However, F(ab')2
fragments of the IgG3 were sufficient to agglutinate type B red blood cells;
therefore, IgG3-triggered agglutination did not require oligomerization.
Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than
other mouse IgG subclasses and that the unique properties of mouse IgG3 are
likely due to the structure of its hinge region. With a focus on applications in
diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood
typing reagents using an accelerated storage approach and differential scanning
calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid
decrease in IgM activity was caused by aggregation of the molecules and a
previously unknown posttranslational proteolytic processing of the MU heavy
chain. Our data point to mouse IgG3 as a potent diagnostic tool.
PMID- 27484489
TI - Nutrition Therapy in Critically Ill Patients Following Cardiac Surgery: Defining
and Improving Practice.
AB - BACKGROUND: Malnutrition is a predictor of poor outcome following cardiac
surgery. We define nutrition therapy after cardiac surgery to identify
opportunities for improvement. METHODS: International prospective studies in 2007
2009, 2011, and 2013 were combined. Sites provided institutional and patient
characteristics from intensive care unit (ICU) admission to ICU discharge for a
maximum of 12 days. Patients had valvular, coronary artery bypass graft (CABG)
surgery, or combined procedures and were mechanically ventilated and staying in
the ICU for >=3 days. RESULTS: There were 787 patients from 144 ICUs. In total,
120 patients (15.2%) had valvular surgery, 145 patients (18.4%) had CABG, and 522
patients (66.3%) underwent a combined procedure. Overall, 60.1% of patients
received artificial nutrition support. For these patients, 78% received enteral
nutrition (EN) alone, 17% received a combination of EN and parenteral nutrition
(PN), and 5% received PN alone. The remaining 314 patients (40%) received no
nutrition. The mean (SD) time from ICU admission to EN initiation was 2.3 (1.8)
days. The adequacy of calories was 32.4% +/- 31.9% from EN and PN and 25.5% +/-
27.9% for patients receiving only EN. In EN patients, 57% received promotility
agents and 20% received small bowel feeding. There was no significant
relationship between increased energy or protein provision and 60-day mortality.
CONCLUSION: Postoperative cardiac surgery patients who stay in the ICU for 3 or
more days are at high risk for inadequate nutrition therapy. Further studies are
required to determine if targeted nutrition therapy may alter clinical outcomes.
PMID- 27484490
TI - The Cost and Outcome Effectiveness of Total Hip Replacement: Technique Choice and
Volume-Output Effects Matter.
AB - BACKGROUND: Total hip replacement (THR) must be managed in a more sustainable
manner. More cost-effective surgical techniques and the
centralization/regionalization of services are two solutions. The former requires
an assessment of newer minimally invasive and muscle-sparing surgical techniques.
The latter necessitates an effective volume-outcome (VO) relationship. Prior
studies have failed to evaluate and control for the VO relation. OBJECTIVE: The
objective of this study was to evaluate the relative cost and outcome
effectiveness of two minimally invasive and one muscle-sparing techniques while
evaluating and controlling for a potentially endogenous VO relation. METHODS: An
all payer claims database for all THR performed in Maine in 2011 was used. The
cost and outcome effectiveness of newer minimally invasive (modified Hardinge)
and muscle-sparing (modified Watson-Jones) techniques were compared with the
standard bearer posterior minimally invasive method. Using regression analysis,
the outcomes analyzed were as follows: total costs, length of hospital stay,
nursing care and home discharges, and use of physical therapy. Regression
analysis was also used to evaluate and control for VO effects. RESULTS: (1) Newer
muscle-sparing and minimally invasive approaches are substantially more
effective; (2) irrespective of technique, higher volume surgeons are more
effective; (3) technique-specific VO effects for more complex techniques exist
and show substantial savings when yearly volume exceeds 30-50; and (4) the
anterolateral muscle-sparing technique is accessible to the average surgeon.
CONCLUSION: Reliance on newer surgical techniques and
centralization/regionalization of THR services can reduce costs.
PMID- 27484491
TI - Investigation of mechanisms of vagus nerve stimulation for seizure using finite
element modeling.
AB - OBJECTIVE: While the efficacy of vagus nerve stimulation (VNS) to reduce seizures
in pharmaco-resistant patients is clinically proven, its efficacy and side
effects mechanisms are not fully understood. Our goals were 1) to use a finite
element model (FEM) and axon models to examine different fiber activation and
blocking thresholds and 2) examine fiber activation and blocking in three fiber
groups likely to be responsible for efficacy and side effects. METHODS: Using
FEM, we examined the field potential along axons within a vagus nerve model with
fascicles. These data were input to a computational fiber model to estimate
numbers of axons activated across all diameters. We estimated numbers of
activated and blocked fibers by diameter. RESULTS: 1) At the low end of VNS
amplitudes, little efficacy for seizure control is appreciated while large Abeta
fibers associated with the recurrent laryngeal nerve are recruited. As amplitudes
are increased, Abeta fibers can produce hoarseness, and next recruited are fast B
fibers associated with the aortic fascicle. We hypothesize these B fibers are the
source of efficacy in treating seizure. As amplitudes are further increased,
coughing may occur, possibly due to recruitment of smaller and deeper pulmonary
fibers. 2) Clinical parameters are in a range that could cause inadvertent
blocking at the cathode and activation at the anode. Conversely, innovative
approaches to field shape and charge-balancing can allow controlled fiber
activation at the cathode for maximum activation of the fibers responsible for
efficacy, and possibly blocking at the anode to minimize side effects and expand
therapeutic range. In design and operation, the cathode and anode can each be
approached as a band pass filter. SIGNIFICANCE: The B fiber group is necessary
and possibly sufficient to produce VNS efficacy in epilepsy. This group may
emanate from aortic baroreceptors that, via synapses in the solitary tract
nucleus, stimulate the locus coeruleus, hypothalamus and other influential
targets such as the hippocampus. Responder rates may be increased with a lead
that fully encircles the nerve. With better identification of the fiber groups
involved in VNS, efficacy, side effects, therapeutic range and responder rates
can be optimized.
PMID- 27484492
TI - Pre-Clinical Study of a Novel Recombinant Botulinum Neurotoxin Derivative
Engineered for Improved Safety.
AB - Cyto-012 is a recombinant derivative of Botulinum neurotoxin Type A (BoNT/A). It
primarily differs from wild type (wt) BoNT/A1 in that it incorporates two amino
acid substitutions in the catalytic domain of the light chain (LC)
metalloprotease (E224 > A and Y366 > A), designed to provide a safer clinical
profile. Cyto-012 is specifically internalized into rat cortical and hippocampal
neurons, and cleaves Synaptosomal-Associated Protein 25 (SNAP-25), the substrate
of wt BoNT/A, but exhibits slower cleavage kinetics and therefore requires a
higher absolute dose to exhibit pharmacologic activity. The pharmacodynamics of
Cyto-012 and wt BoNT/A have similar onset and duration of action using the
Digital Abduction Assay (DAS). Intramuscular LD50 values for Cyto-012 and wt
BoNT/A respectively, were 0.63 ug (95% CI = 0.61, 0.66) and 6.22 pg (95% CI =
5.42, 7.02). ED50 values for Cyto-012 and wt BoNT/A were respectively, 0.030 ug
(95% CI = 0.026, 0.034) and 0.592 pg (95% CI = 0.488, 0.696). The safety margin
(intramuscular LD50/ED50 ratio) for Cyto-012 was found to be improved 2-fold
relative to wt BoNT/A (p < 0.001). The DAS response to Cyto-012 was diminished
when a second injection was administered 32 days after the first. These data
suggest that the safety margin of BoNT/A can be improved by modulating their
activity towards SNAP-25.
PMID- 27484493
TI - Perceptions of childhood undernutrition among rural households on the Kenyan
coast - a qualitative study.
AB - BACKGROUND: Nutrition plays an important role in child survival and development.
Treatment action in the management of child health and nutrition is influenced by
perceptions of illness, and gender plays an important role. However, little is
known about if and how moderate undernutrition is recognised among lay
populations, or how local social norms and intra-household dynamics affect
decisions to seek biomedical assistance for nutritional concerns. In this paper
we describe how childhood nutritional problems are recognised and understood
within rural households. We demonstrate how context influences local constructs
of 'normal', and suggest the centrality of gender in the management of child
health and nutrition in our research context. METHODS: This qualitative study was
undertaken in Kilifi County on the Kenyan Coast. A set of 15 households whose
children were engaged in a community-based nutrition intervention were followed
up over a period of twelve months. Over a total of 54 household visits, group and
individual in-depth interviews were conducted with a range of respondents,
supplemented by non-participant observations. Eight in-depth interviews with
community representatives were also conducted. RESULTS: Local taxonomies of
childhood undernutrition were found to overlap with, but differ from, biomedical
categories. In particular, moderate undernutrition was generally not recognised
as a health problem requiring treatment action, but rather as routine and
manageable, typically seasonal, weight-loss. Where symptoms were considered more
serious and requiring remedial action, household management strategies were
typically based on perceived aetiology of the illness. Additionally, gender
emerged as a potentially central theme in childhood nutrition problems and
related management. Women reported that they have primary responsibility for
ensuring children's good health and nutritional status, and that they are often
held accountable when their children are of sub-optimal health. CONCLUSION:
Perceptions of child nutrition and illness and gendered roles within households
influence treatment action, and engagement with nutrition interventions.
Community-based nutrition interventions must recognise these complex realities.
PMID- 27484494
TI - [Chronic coronary occlusions : When and how should revascularization be
performed?]
AB - Chronic occlusion of coronary arteries also known as chronic total occlusions
(CTO) are found in approximately 20 % of patients undergoing percutaneous
coronary interventions (PCI) and in approximately 50 % of patients after coronary
artery bypass grafts (CABG). As a result of technical advancements in retrograde
recanalization techniques specialized centers can now achieve success rates of
over 85 %, regardless of the CTO anatomy. Given the complexity of retrograde CTO
techniques, a consensus paper issued by the Euro CTO Club requires interventional
cardiologists to have sufficient experience in antegrade approaches (>300
antegrade CTO cases and >50 per year) with an additional training program (25
retrograde cases each as first and second operating surgeon) before becoming a
qualified independent retrograde surgeon. The increased investment in time and
technical resources can only be justified if the patient has a clear clinical
benefit. This technical advancement and the progressively clearer evidence that
complete revascularization can be achieved in patients with multivessel coronary
artery disease have attracted growing interest in recent years from
interventional cardiologists in the recanalization of CTO.
PMID- 27484495
TI - Kidney epithelium specific deletion of kelch-like ECH-associated protein 1
(Keap1) causes hydronephrosis in mice.
AB - BACKGROUND: Transcription factor Nrf2 protects from experimental acute kidney
injury (AKI) and is promising to limit progression in human chronic kidney
disease (CKD) by upregulating multiple antioxidant genes. We recently
demonstrated that deletion of Keap1, the endogenous inhibitor of Nrf2, in T
lymphocytes significantly protects from AKI. In this study, we investigated the
effect of Keap1 deletion on Nrf2 mediated antioxidant response in the renal
tubular epithelial cells. METHODS: We deleted Keap1 exon 2 and 3 in the renal
tubular epithelial cells by crossing Ksp-Cre mice with Keap1 floxed (Keap1 (f/f))
mice. Deletion of Keap1 gene in the kidney epithelial cells of Ksp-Keap1 (-/-)
mice and its effect on Nrf2 target gene expression was performed using PCR and
real-time PCR respectively. Histological evaluation was performed on H&E stained
sections. Complete blood count, serum and urine analysis were performed to assess
systemic effects of defective kidney development. Student's T test was used to
determine statistical difference between the groups. RESULTS: Ksp-Cre resulted in
the deletion of Keap1 exon 2 and 3 and subsequent upregulation of Nrf2 target
genes, Nqo1, Gclm and Gclc in the kidney epithelial cells of Ksp-Keap1 (-/-) mice
at baseline. Renal epithelial cell specific deletion of Keap1 in Ksp-Keap1 (-/-)
mice caused marked renal pelvic expansion and significant compression of
medullary parenchyma consistent with hydronephrosis in both (3 month-old) males
and females. Kidneys from 6 month-old Ksp-Keap1 (-/-) mice showed progressive
hydronephrosis. Hematological, biochemical and urinary analysis showed
significantly higher red blood cell count (p = 0.04), hemoglobin (p = 0.01),
hematocrit (p = 0.02), mean cell volume (p = 0.02) and mean cell hemoglobin
concentration (p = 0.003) in Ksp-Keap1 (-/-) mice in comparison to Keap1 (f/f)
mice. CONCLUSIONS: These unexpected findings demonstrate that Keap1 deletion in
renal tubular epithelial cells results in an abnormal kidney development
consistent with hydronephrosis and reveals a novel Keap1 mediated signaling
pathway in renal development.
PMID- 27484496
TI - Numerical Bifurcation Analysis of Physiologically Structured Populations:
Consumer-Resource, Cannibalistic and Trophic Models.
AB - With the aim of applying numerical methods, we develop a formalism for
physiologically structured population models in a new generality that includes
consumer-resource, cannibalism and trophic models. The dynamics at the population
level are formulated as a system of Volterra functional equations coupled to ODE.
For this general class, we develop numerical methods to continue equilibria with
respect to a parameter, detect transcritical and saddle-node bifurcations and
compute curves in parameter planes along which these bifurcations occur. The
methods combine curve continuation, ODE solvers and test functions. Finally, we
apply the methods to the above models using existing data for Daphnia magna
consuming Algae and for Perca fluviatilis feeding on Daphnia magna. In
particular, we validate the methods by deriving expressions for equilibria and
bifurcations with respect to which we compute errors, and by comparing the
obtained curves with curves that were computed earlier with other methods. We
also present new curves to show how the methods can easily be applied to derive
new biological insight. Schemes of algorithms are included.
PMID- 27484497
TI - Comfort experience in palliative care: a phenomenological study.
AB - BACKGROUND: Palliative care aims to provide maximum comfort to the patient.
However it is unknown what factors facilitate or hinder the experience of
comfort, from the perspective of inpatients of palliative care units. This lack
of knowledge hinders the development of comfort interventions adjusted to these
patients. The aim of this research is to describe the comfort and discomfort
experienced by inpatients at palliative care units. METHODS: A phenomenological
descriptive study was undertaken. Ten inpatients were recruited from a Spanish
palliative care unit and seven from a Portuguese palliative care unit. Data were
collected using individual interviews and analysed following the method of
Giorgi. RESULTS: Four themes reflect the essence of the lived experience: The
Palliative Care as a response to the patient's needs with advanced disease,
attempt to naturalize advanced disease, confrontation with their own
vulnerability, openness to the spiritual dimension. CONCLUSIONS: Informants
revealed that they experience comfort through humanized care, differentiated
environment, symptomatic control, hope and relationships. The discomfort emerges
from the losses and powerlessness against their situation. Even if such findings
may seem intuitive, documenting them is essential because it invites us to
reflect on our convictions about what it means to be comfortable for these
patients, and allows incorporating this information in the design of focused
interventions to maximize the comfort experience.
PMID- 27484498
TI - Systems Pharmacology Dissection of the Protective Effect of Myricetin Against
Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart.
AB - In this paper, we investigated the multi-target effect of myricetin as a
therapeutic for cardiovascular disease, using an acute ischemia/reperfusion
induced myocardial injury model to gain insight into its mechanism of action. The
compound-target interaction profiles of myricetin were determined using a
combination of text mining, chemometric and chemogenomic methods. The effect of
myricetin on cardiac function was investigated by carrying out experiments in
rats subjected to ischemia/reperfusion (I/R) using Langendorff retrograde
perfusion technology. Compared to the I/R group, pretreatment with 5 MUM
myricetin was observed to improve the maximum up/down rate of left ventricular
pressure (dp/dt max) and coronary flow, raise left ventricular developed
pressure, and decrease creatine kinase and lactate dehydrogenase levels in
coronary flow. In addition, myricetin treatment was shown to have beneficial
effects through its ability to reduce both infarct size and levels of
cardiomyocyte apoptosis. Myricetin was also observed to have antioxidant
properties, as evidenced by its ability to reduce MDA levels, while increasing
both SOD levels and the GSH/GSSG ratio. Finally, an upregulation of 6
phosphogluconate dehydrogenase and fatty acid synthase expression and a
downregulation of cyclooxygenase-2, cytochrome P450 and p38 mitogen-activated
protein kinase expression suggest that myricetin acts through mechanisms which
alter relevant signaling pathways. In summary, our results demonstrate that
myricetin has protective cardiovascular effects against I/R-induced myocardial
injury.
PMID- 27484499
TI - Safety and efficacy in ablation of premature ventricular contraction: data from
the German ablation registry.
AB - BACKGROUND: Patients with frequent premature ventricular contractions (PVCs) are
often highly symptomatic with significantly reduced quality-of-life. We evaluated
the outcome and success of PVC ablation in patients in the German Ablation
Registry. METHODS: The German Ablation Registry is a nationwide prospective
multicenter database of patients who underwent an ablation procedure, initiated
by the "Stiftung Institut fur Herzinfarktforschung" (IHF), Ludwigshafen, Germany.
Data were acquired from March 2007 to May 2011. Patients underwent PVC ablation
in the enrolling ablation centers. RESULTS: A total of 408 patients (age 53.5 +/-
15 years, 55 % female) undergoing ablation for PVCs were included. 32 % of
patients showed a co-existing structural heart disease. Acute ablation success of
the procedure was 82 % in the overall patient group. In patients without
structural heart disease, acute success was significantly higher compared with
patients with structural heart disease (86 vs. 74 %, p = 0.002). All patients
were discharged alive after a median of 3 days. No patient suffered an acute
myocardial infarction, stroke, or major bleeding. After 12 months' follow-up, 99
% of patients were still alive showing a significant different mortality between
patients with structural heart disease compared with those without (2.3 vs. 0 %,
p = 0.012). In addition, 76 % of patients showed significantly improved symptoms
after 12 months of follow-up. CONCLUSION: Based on the data from this registry,
ablation of PVCs is a safe and efficient procedure with an excellent outcome and
improved symptoms after 12 months.
PMID- 27484500
TI - Biological study of the effect of water soluble [N-(2-hydroxybenzyl)-L-aspartato]
gallium complexes on breast carcinoma and fibrosarcoma cells.
AB - Two water soluble gallium complexes described as [Ga(III)LCl], where L is the
deprotonated form of N-2-hydroxybenzyl aspartic acid derivatives, were
synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry,
and elemental analysis. The 2-(5-chloro-2-hydroxybenzylamino)succinic acid
derivative (GS2) has been found to be a promising anticancer drug candidate. This
compound was found to be more cytotoxic against human breast carcinoma MDA-MB231
and fibrosarcoma HT-1080 cell lines than the unsubstituted derivative and GaCl3.
GS2 was able to induce apoptosis through downregulation of AKT phosphorylation,
G2M arrest in cell cycle, and caspase 3/7 pathway. This gallium complex was found
to induce an increase in mitochondrial ROS level in HT-1080 cells but not in MDA
MB231 cells. This suggests that the mechanism of action of GS2 would not be
mediated by the drug-induced oxidative stress but probably by directly and
indirectly inhibiting the AKT cell-signaling pathway.
PMID- 27484501
TI - Immunomodulatory Properties of Mesenchymal Stem Cells Can Mitigate Oxidative
Stress and Inflammation Process in Human Mustard Lung.
AB - Oxidative stress and inflammation are one of the main pathological consequences
of sulfur mustard on human lungs. Unfortunately, there is no effective treatment
to mitigate pathological effects of sulfur mustard in mustard lungs. Here, we
aimed to evaluate potential efficacy of systemic mesenchymal stem cells
administration on expression of oxidative stress- and inflammation-related genes
in sulfur mustard-exposed patients. Our patient received 100 million cells per
injection, which was continued for four injections within 2 months. Sputum
samples were provided after each injection. Oxidative stress was evaluated by
determining sputum levels of malondialdehyde and glutathione. Furthermore,
changes in expression of several oxidative stress- (metallothionein 3,
glutathione reductase, oxidative stress responsive 1, glutathione peroxidase 2,
lacto peroxidase, forkhead box M1) and inflammation-related genes (matrix
metallopeptidase 2, matrix metallopeptidase 9, transforming growth factor-beta1,
vascular endothelial growth factor, metallopeptidase inhibitor 1,
metallopeptidase inhibitor 2) were also evaluated using real-time PCR after
treatments. Two-lung epithelial-specific proteins including Clara cell protein 16
and Mucin-1 protein levels were measured using enzyme immunoassay method. No
significant differences were found between serum levels of Clara cell protein 16
and serum Mucin-1 protein in patient before and after cell therapy. Most of the
oxidative stress responsive genes, particularly oxidative stress responsive 1,
were overexpressed after treatments. Expressions of antioxidants genes such as
metallothionein 3, glutathione reductase and glutathione peroxidase 2 were
increased after cell therapy. Upon comparison of inflammation-related genes, we
observed upregulation of vascular endothelial growth factor and matrix
metallopeptidase 9 after mesenchymal stem cells therapy. Additionally, a trend
for increased value of glutathione and decreased levels of malondialdehyde was
observed from baseline to final evaluation times. Mesenchymal stem cells
administration mitigates oxidative stress and inflammation in sulfur mustard
exposed patients.
PMID- 27484502
TI - Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible
tolerance to cancer drugs.
AB - Acquired resistance to cancer drug therapies almost always occurs in advanced
stage patients even following a significant response to treatment. In addition to
mutational mechanisms, various non-mutational resistance mechanisms have now been
recognized. We previously described a chromatin-mediated subpopulation of
reversibly drug-tolerant persisters that is dynamically maintained within a wide
variety of tumour cell populations. Here we explore a potential role for
microRNAs in such transient drug tolerance. Functional screening of 879 human
microRNAs reveals miR-371-3p as a potent suppressor of drug tolerance. We
identify PRDX6 (peroxiredoxin 6) as a key target of miR-371-3p in establishing
drug tolerance by regulating PLA2/PKCalpha activity and reactive oxygen species.
PRDX6 expression is associated with poor prognosis in cancers of multiple tissue
origins. These findings implicate miR-371-3p as a suppressor of PRDX6 and suggest
that co-targeting of peroxiredoxin 6 or modulating miR-371-3p expression together
with targeted cancer therapies may delay or prevent acquired drug resistance.
PMID- 27484503
TI - Patterns of Primary Immunodeficiency Disorders Among a Highly Consanguineous
Population: Cairo University Pediatric Hospital's 5-Year Experience.
AB - INTRODUCTION: Primary immunodeficiency disorders (PIDs) are heterogeneous
disorders that mainly present with severe, persistent, unusual, or recurrent
infections in childhood. Reports from different parts of the world indicate a
difference between Western and Eastern populations. AIM: The aim of this study
was to report on the different patterns of PIDs and identify subgroup
characteristics in a highly consanguineous population in Egypt. METHODS: We
performed a retrospective chart review for children below 18 years diagnosed with
PID at Cairo University Pediatric Hospital from 2010 to 2014. RESULTS: Four
hundred seventy-six children were diagnosed with PID disorders. Major categories
included combined immunodeficiency disorders, which constituted a large
proportion (30 %) of cases, along with predominantly antibody disorders (18 %)
followed by syndromic combined disorders (16.8 %), phagocytic disorders (13.2 %),
immune dysregulation disorders (10.5 %), and autoinflammatory disorders (9 %).
CONCLUSION: PIDs have different patterns within inbred populations with high
consanguinity.
PMID- 27484504
TI - Phenotypic and Functional Comparison of Class Switch Recombination Deficiencies
with a Subgroup of Common Variable Immunodeficiencies.
AB - Primary antibody deficiencies (PADs) are the most common immunodeficiency in
humans, characterized by low levels of immunoglobulins and inadequate antibody
responses upon immunization. These PADs may result from an early block in B cell
development with a complete absence of peripheral B cells and lack of
immunoglobulins. In the presence of circulating B cells, some PADs are
genetically caused by a class switch recombination (CSR) defect, but in the most
common PAD, common variable immunodeficiency (CVID), very few gene defects have
as yet been characterized despite various phenotypic classifications. Using a
functional read-out, we previously identified a functional subgroup of CVID
patients with plasmablasts (PBs) producing IgM only. We have now further
characterized such CVID patients by a direct functional comparison with patients
having genetically well-characterized CSR defects in CD40L, activation-induced
cytidine deaminase (AID) and uracil N-glycosylase activity (UNG). The CSR-like
CVID patients showed a failure in B cell activation patterns similar to the
classical AID/UNG defects in three out of five CVID patients and distinct more
individual defects in the two other CVID cases when tested for cellular
activation and PB differentiation. Thus, functional categorization of B cell
activation and differentiation pathways extends the expected variation in CVID to
CSR-like defects of as yet unknown genetic etiology.
PMID- 27484505
TI - The shouted voice: A pilot study of laryngeal physiology under extreme
aerodynamic pressure.
AB - INTRODUCTION: The objective was to study the behavior of the larynx during
shouted voice production, when the larynx is exposed to extremely high subglottic
pressure. MATERIALS AND METHODS: The study involved electroglottographic,
acoustic, and aerodynamic analyses of shouts produced at maximum effort by three
male participants. RESULTS AND DISCUSSION: Under a normal speaking voice, the
voice sound pressure level (SPL) is proportional to the subglottic pressure.
However, when the subglottic pressure reached high levels, the voice SPL reached
a maximum value and then decreased as subglottic pressure increased further.
Furthermore, the electroglottographic signal sometimes lost its periodicity
during the shout, suggesting irregular vocal fold vibration.
PMID- 27484506
TI - Soleal vein dilatation assessed by ultrasonography is an independent predictor
for deep vein thrombosis after major orthopedic surgery.
AB - BACKGROUND: Deep vein thrombosis (DVT) develops after major orthopedic surgery
despite the current use of prophylaxis. DVT frequently develops in the soleal
vein (SV) and might develop easily at the site of SV dilatation because of blood
flow stasis. However, whether preoperative SV dilatation detected by
ultrasonography predicts DVT after major orthopedic surgery remains unknown.
OBJECTIVE: We examined whether SV dilatation detected by preoperative
ultrasonography predicts DVT after major orthopedic surgery. METHODS:
Ultrasonography was performed preoperatively and postoperatively in 243 patients
with orthopedic diseases (mean age of 67+/-13 years, 77% women) who underwent
total hip arthroplasty (THA, n=180) or total knee arthroplasty (TKA, n=63).
Presence of DVT was diagnosed by ultrasonography and SV diameter >=10mm was
defined as SV dilatation. Patients with preoperative DVT were excluded. RESULTS:
Sixty-nine patients (28%) developed postoperative DVT. SV dilatation was found in
24 patients (10%), and 16 (67%) of those patients had postoperative DVT.
Multivariate logistic regression analysis showed that female gender [odds ratio
(OR): 4.09, p=0.004], TKA (OR: 2.52, p=0.011), and SV dilatation (OR: 6.67,
p<0.001), but not presence of comorbidities, medications, or plasma d-dimer
value, independently predict postoperative DVT. Subgroup analyses according to
the operation site showed that female gender (OR: 3.27, p=0.043) and SV
dilatation (OR: 3.72, p=0.022) were independent predictors of postoperative DVT
in the THA group. SV dilatation (OR: 12.0, p=0.027) was an independent predictor
of postoperative DVT also in the TKA group. CONCLUSIONS: In addition to gender
and TKA, SV dilatation detected by ultrasonography is an independent predictor of
DVT after major orthopedic surgery. Determination of SV diameter by
ultrasonography before major orthopedic surgery is useful for assessing the risk
of postoperative DVT.
PMID- 27484508
TI - Identification of new potent phthalazine derivatives with VEGFR-2 and EGFR kinase
inhibitory activity.
AB - Efforts to develop new antitumor agents are now directed towards multitarget
therapies that are believed to have high potency and low tendency to resistance
compared to conventional drugs. Herein, we highlighted the synthesis and
antitumor activity of five series of phthalazine-based compounds featuring a
variety of bioactive chemical fragments at position 1 of the phthalazine nucleus.
The antitumor activity of the target compounds was performed against fourteen
cancer cell lines where all compounds were active in the nanomolar level. In
addition, the mechanism of action of the target compounds was investigated
through an enzymatic inhibitory assay against VEGFR-2 and EGFR kinases, revealing
potent and preferential activity toward VEGFR-2. Binding mode of the most active
compounds was studied using docking experiment.
PMID- 27484507
TI - Effect of inspiratory muscle training with load compared with sham training on
blood pressure in individuals with hypertension: study protocol of a double-blind
randomized clinical trial.
AB - BACKGROUND: Hypertension is a complex chronic condition characterized by elevated
arterial blood pressure. Management of hypertension includes non-pharmacologic
strategies, which may include techniques that effectively reduce autonomic
sympathetic activity. Respiratory exercises improve autonomic control over
cardiovascular system and attenuate muscle metaboreflex. Because of these
effects, respiratory exercises may be useful to lower blood pressure in subjects
with hypertension. METHODS/DESIGN: This randomized, double-blind clinical trial
will test the efficacy of inspiratory muscle training in reducing blood pressure
in adults with essential hypertension. Subjects are randomly allocated to
intervention or control groups. Intervention consists of inspiratory muscle
training loaded with 40 % of maximum inspiratory pressure, readjusted weekly.
Control sham intervention consists of unloaded exercises. Systolic and diastolic
blood pressures are co-primary endpoint measures assessed with 24 h ambulatory
blood pressure monitoring. Secondary outcome measures include cardiovascular
autonomic control, inspiratory muscle metaboreflex, cardiopulmonary capacity, and
inspiratory muscle strength and endurance. DISCUSSION: Previously published work
suggests that inspiratory muscle training reduces blood pressure in persons with
hypertension, but the effectiveness of this intervention is yet to be
established. We propose an adequately sized randomized clinical trial to test
this hypothesis rigorously. If an effect is found, this study will allow for the
investigation of putative mechanisms to mediate this effect, including autonomic
cardiovascular control and metaboreflex. TRIAL REGISTRATION: ClinicalTrials.gov
NCT02275377 . Registered on 30 September 2014.
PMID- 27484509
TI - Design, synthesis and evaluation of pyrazole derivatives as non-nucleoside
hepatitis B virus inhibitors.
AB - In continuation of our efforts toward the discovery of potent non-nucleoside
hepatitis B virus (HBV) inhibitors with novel structures, we have employed
bioisosterism and hybrid pharmacophore-based strategy to explore the chemically
diverse space of bioactive compounds. In this article, the original thiazole
platform was replaced with pyrazole scaffold to yield the optimal pharmacophore
moieties in order to generate novel non-nucleoside HBV inhibitors with desirable
potency. Some of the new compounds were able to inhibit HBV activity in the low
micromolar range. In particular, compound 6a3 displayed the most potent activity
against the secretion of HBsAg and HBeAg with IC50 of 24.33 MUM and 2.22 MUM,
respectively. The preliminary structure-activity relationship (SAR) of this new
series of compounds was investigated, which may help designing more potent
molecules.
PMID- 27484510
TI - Synthesis and biological evaluation of C1-O-substituted-3-(3-butylamino-2-hydroxy
propoxy)-xanthen-9-one as topoisomerase IIalpha catalytic inhibitors.
AB - Topoisomerase II poison blocks the transitorily generated DNA double-strand
breaks (DSBs) from religation, thereby causes severe DNA damage and gene
toxicity. While topoisomerase II catalytic inhibitor does not form cleavable DNA
enzyme complex because its function attributes to inhibition of the catalytic
steps of the enzyme such as before generating DNA DSBs or in the last step of the
catalytic cycle after religation. It has been reported that the stabilizing
effect of etoposide on transient cleavable DNA-topoisomerase IIbeta complex
attributes to its secondary malignancy. Therefore, topoisomerase IIalpha has been
considered as more attractive target than topoisomerase IIbeta for the
development of chemotherapeutic agents. In the previous work, we reported
compounds I and II as novel topoisomerase IIalpha catalytic inhibitors targeting
for ATP binding site of human topoisomerase IIalpha ATP-binding domain. As a
continuous work, we have designed and synthesized 43 compounds of C1-O-alkyl and
arylalkyl substitiuted compounds with or without methoxy group on ring A. In the
topoisomerase IIalpha inhibitory test, among the tested C1-O-4-chlorophenethyl
substituted compounds 37 and 47 were more active than others, and compound 37
showed strongest topoisomerase IIalpha inhibitory activity with 94.4% and 23.0%
inhibition, respectively, at 100 and 20 MUM. Compounds 37 and 47 have also showed
much enhanced cytotoxic activity against T47D cells; IC50 (MUM): 0.63 +/- 0.01
and 0.19 +/- 0.02, respectively, which are stronger than reference drugs. Band
depletion assay and cleavage complex assay results showed compounds 37 and 47
were potential topoisomerase IIalpha catalytic inhibitor with low DNA damage.
PMID- 27484511
TI - Aromatic heterocyclic esters of podophyllotoxin exert anti-MDR activity in human
leukemia K562/ADR cells via ROS/MAPK signaling pathways.
AB - Currently, multi-drug resistance (MDR) to antineoplastic drugs is a major
obstacle to successful treatment of carcinoma. Looking for novel agents with anti
MDR activity is an effectively way to overcome cancer drug resistance. Our
previous study showed that podophyllotoxin derivative exhibited potent anti
proliferative effect and down-regulated the expression level of P-gp in K562/ADR
cells, which probably was related with the MAPK pathways. However, the relation
of P-gp expression and MAPK pathways still remains unclear. In this study, a
series of aromatic heterocyclic esters of podophyllotoxin were synthesized and
their anticancer effects were evaluated against two human chronic myeloid
leukemia cell lines (K562 and K562/ADR), simultaneously, the initial structure
activity relationship was summarized. The most potent compound, Z5, displayed an
IC50 value of 0.032 +/- 0.006 MUM against K562/ADR cells, with a lower resistant
factor value of 1.280. Treatment of K562/ADR cells with Z5 caused S cell cycle
arrest through reductions in cyclinA, cyclinB1, CDK1 and CDK2 levels. Moreover,
Z5 treatment resulted in the induction of apoptosis as characterized by DNA
staining, flow cytometry analysis and cleavage of procaspases-3, -8, -9 and PARP.
Notably, Z5 significantly inhibited P-gp expression in K562/ADR cells.
Additionally, Z5 also caused reactive oxygen species (ROS) generation, which was
further demonstrated by preincubation with the antioxidant N-acetylcysteine
(NAC). Western blotting revealed that Z5 markedly stimulated the MAPK pathways,
including ERK1/2, JNK and P38, however, the mechanisms were prevented by NAC.
Finally, the employment of NAC and MAPK inhibitors (U0126, SP600125 and SB203580)
remarkably blocked the S phase arrest, apoptosis and down-regulation of P-gp
induced by Z5. Taken together, Z5 strongly possessed the potential anti-MDR
activity in K562/ADR cells through ROS/MAPK pathways-dependent S phase arrest,
apoptosis and down-regulation of P-gp expression.
PMID- 27484512
TI - Therapeutic potential of coumarins as antiviral agents.
AB - Coumarins have received a considerable attention in the last three decades as a
lead structures for the discovery of orally bioavailable non-peptidic antiviral
agents. A lot of structurally diverse coumarins analogues were found to display
remarkable array of affinity with the different molecular targets for antiviral
agents and slight modifications around the central motif result in pronounced
changes in its antiviral spectrum. This manuscript thoroughly reviews the design,
discovery and structure-activity relationship studies of the coumarin analogues
as antiviral agents focusing mainly on lead optimization and its development into
clinical candidates.
PMID- 27484513
TI - The therapeutic journey of pyridazinone.
AB - Pyridazinones have drawn a substantial attention within the field of research
analysis and development. The moiety is a subject matter of intensive research
because of its wide spectrum of biological activities and therapeutic
applications. The synthesis of pyridazinone and investigation of their chemical
and biological activities have gained additional importance in recent years. In
this review, we have compiled and discussed various biological and therapeutic
potential of pyridazinone derivatives.
PMID- 27484514
TI - Rational modification of donepezil as multifunctional acetylcholinesterase
inhibitors for the treatment of Alzheimer's disease.
AB - A series of novel donepezil derivatives was designed, synthesized and evaluated
as multifunctional acetylcholinesterase (AChE) inhibitors for the treatment of
Alzheimer's disease (AD). The screening results indicated that most of the
compounds exhibited potent inhibition of AChE with IC50 values in the nanomolar
range. Moreover, these derivatives displayed good antioxidant, Abeta interaction,
blood-brain barrier penetration (PAMPA-BBB+) and ADMET properties (in silico).
Among them, 5c demonstrated excellent AChE inhibition (IC50: 85 nM for eeAChE, 73
nM for hAChE), metal chelation, and inhibitory effects on self-induced, hAChE
induced and Cu(2+)-induced Abeta1-42 aggregation (18.5%, 72.4% and 46.3%, at 20
MUM). Kinetic analysis and molecular modeling studies suggested that 5c could
bind simultaneously to the catalytic active site (CAS) and peripheral anionic
site (PAS) of AChE. More importantly, 5c exhibited significant neuroprotective
potency against Abeta1-42-induced PC12 cell injury. Furthermore, the step-through
passive avoidance test showed 5c significantly reversed scopolamine-induced
memory deficit and no hepatotoxicity in mice. These results indicated that 5c
might be a promising drug candidate for AD therapy.
PMID- 27484515
TI - Synthesis and structure-activity relationship study of tacrine-based pyrano[2,3
c]pyrazoles targeting AChE/BuChE and 15-LOX.
AB - A series of tacrine-based pyrazolo[4',3':5,6]pyrano[2,3-b]quinolines and related
compounds were designed and synthesized for targeting AChE, BuChE and 15-LOX
enzymes in the field of Alzheimer's disease therapy. Most of compounds showed
potent activity against cholinesterases and mild potency toward 15-LOX enzyme. In
particular, compounds 29, 32 and 40 displayed inhibition at nano-molar level
against AChE and BuChE (IC50s = 0.005-0.08 MUM), being more potent than reference
drug tacrine. Moreover, compound 32 with IC50 value of 31 MUM was the most potent
compound against 15-LOX. The cytotoxicity assay on HepG2 cells revealed that
compounds 29 and 32 showed no significant cytotoxic activity even at
concentration of 50 MUM. The cytotoxicity of compounds 29 and 32 was
significantly less than that of tacrine at higher concentrations.
PMID- 27484516
TI - 2,4,5-Trisubstituted thiazole derivatives as HIV-1 NNRTIs effective on both wild
type and mutant HIV-1 reverse transcriptase: Optimization of the substitution of
positions 4 and 5.
AB - In our previous work, novel 2,4,5-trisubstituted thiazole derivatives (TSTs) were
synthesized, and their activities were evaluated against HIV-1 reverse
transcriptase. Some interesting results were obtained, which led us to a new
discovery regarding these TSTs. In the present study, 21 new 2,4,5-trisubstituted
thiazole derivatives were rationally designed and synthesized as HIV-1 non
nucleoside reverse transcriptase inhibitors (NNRTIs) in accordance with our
previous study. Among the synthesized target compounds, compounds 14, 16, 17, and
19 showed more potent inhibitory activities against HIV-1 with an IC50 value of
0.010 MUM. Compounds 4, 9, 10, 11, 13 and 16 were further tested on nine NNRTI
resistant HIV-1 strains, and all of these compounds exhibited inhibitory effects.
A molecular docking study was conducted, and the results showed a consistent and
stable binding mode for the typical compounds. These results have provided deeper
insights and SAR of these types of NNRTIs.
PMID- 27484518
TI - Metal storage in reeds from an acid mine drainage contaminated field.
AB - Phragmites australis has been used to treat acid mine drainage (AMD)-contaminated
soil. However, the mechanism about metal translocation in reeds was not widely
reported. This study investigated metal (Fe, Al, and Mn) storage location in
reeds grown in five different sampling sites of an AMD field. As expected, the
more metals in soil, the more metals entered the belowground organs of plants.
Reeds grown in soils with the highest levels of metals accumulated 0.16 +/- 0.04
mg/g Mn, 16.29 +/- 4.15 mg/g Fe, and 1.31 +/- 0.22 mg/g Al in roots. Most of the
iron was sequestered in the roots, while Al was transferred to the shoots.
Histological staining found that most of the iron was sequestered in the
exodermis, while Al extended the endodermis of roots. Al even entered the stele
of roots grown in soil with higher Al levels. The epidermis, cortex, and central
cylinder of rhizomes were the main tissues for Fe and Al storage. The more metals
in rhizomes, the stronger intensity of the staining was observed around the
vascular systems of rhizomes. No structural difference was observed among reeds
collected from different sites. Further studies may be needed to enhance the
transfer of metals in reeds and increase the phytoremediation efficiency.
PMID- 27484519
TI - Urgent action needed to address key worker housing crisis.
AB - We report this week that a group of nurses living in a block of flats in south
east London faced with a 20% rent hike have been given just 8 weeks to pay up or
move out.
PMID- 27484517
TI - Synthesis and cytotoxic activity of novel A-ring cleaved ursolic acid derivatives
in human non-small cell lung cancer cells.
AB - Ursolic acid (UA) is a pentacyclic triterpenoid with recognized anticancer
properties. We prepared a series of new A-ring cleaved UA derivatives and
evaluated their antiproliferative activity in non-small cell lung cancer (NSCLC)
cell lines using 2D and 3D culture models. Compound 17, bearing a cleaved A-ring
with a secondary amide at C3, was found to be the most active compound, with
potency in 2D systems. Importantly, even in 3D systems, the effect was maintained
albeit a slight increase in the IC50. The molecular mechanism underlying the
anticancer activity was further investigated. Compound 17 induced apoptosis via
activation of caspase-8 and caspase-7 and via decrease of Bcl-2. Moreover,
induction of autophagy was also detected with increased levels of Beclin-1 and
LC3A/B-II and decreased levels of mTOR and p62. DNA synthetic capacity and cell
cycle profiles were not affected by the drug, but total RNA synthesis was
modestly but significantly decreased. Given its activity and mechanism of action,
compound 17 might represent a potential candidate for further cancer research.
PMID- 27484520
TI - Large tax rebates possible for thousands of nurses.
AB - Nurses who took part in an NHS training scheme could be eligible for tax rebates
that may be worth thousands of pounds.
PMID- 27484521
TI - Star turn.
AB - A nursing assistant's moving version of an Adele hit has been viewed thousands of
times around the world.
PMID- 27484522
TI - Staff told to 'back off' over allegations of surgeon misconduct - hearing told.
AB - A senior nurse at an NHS hospital instructed a colleague not to raise concerns
about a surgeon who operated on the wrong finger of a patient, a Nursing and
Midwifery Council (NMC) hearing was told.
PMID- 27484524
TI - Nurse's murder sentence is upheld.
AB - Former nurse Victorino Chua has failed in a bid to challenge his conviction and
sentence.
PMID- 27484525
TI - Rent crisis exposed as key workers hit with 20% hike.
AB - The RCN has called for more affordable accommodation for nurses as key workers in
London faced a 20% rent hike.
PMID- 27484527
TI - Brexit could hit nursing regulator's finances.
AB - The UK's decision to leave the EU could hit the Nursing and Midwifery Council's
income, the regulator has warned.
PMID- 27484528
TI - nursing.standard.com.
AB - 1 The first-ever publication of statistics on female genital mutilation (FGM) has
revealed 5,700 new cases in England over the past year. Nurses, midwives, doctors
and teachers are legally required to report cases of FGM involving girls aged
under 18 to the police. Read more rcni.com/FGM-reporting.
PMID- 27484529
TI - University of Salford's L1.7m training facilities recreate real hospital
environment.
AB - The next generation of nurses and midwives will be honing their skills on
manikins that can breathe, 'speak', sweat and blink at a L1.7 million training
suite at the University of Salford.
PMID- 27484530
TI - Raising awareness with Sir Elton John.
AB - A sexual health nurse joined Sir Elton John and Prince Harry at a conference in
South Africa to raise awareness of HIV/Aids.
PMID- 27484531
TI - Length of service proposal to reduce student debt.
AB - How much graduate nurses repay their student debt could be linked to length of
service in the NHS, a nursing expert has said.
PMID- 27484532
TI - 'Weak' research undermines profession.
AB - The contribution of nursing is being underestimated because of 'weak and small
scale' research, a leading workforce expert has warned.
PMID- 27484533
TI - Call to boost peers with nursing background to House of Lords.
AB - Increasing the number of nurse peers in the House of Lords would give the
profession more political cache, according to a University of Sydney professor of
nursing and midwifery.
PMID- 27484534
TI - Healthcare workers urged to improve hand hygiene to prevent spread of AMR.
AB - Nurses can help to prevent the spread of antimicrobial resistance by improving
their hand hygiene, a health professional has said.
PMID- 27484535
TI - The lasting legacy of #hellomynameis.
AB - Three years ago, while in hospital with a post-operative infection, Kate Granger
discussed with her husband the failure of some staff on a ward to introduce
themselves to her.
PMID- 27484538
TI - Sickle cell disease.
AB - Essential facts Sickle cell disease is a group of disorders of red blood cells
that is believed to affect up to 15,000 people in the UK. The lifelong condition
can have a significant impact on morbidity and mortality.
PMID- 27484539
TI - Rise in alcohol tax could cut violence-related A&E visits.
AB - A small rise in alcohol duty could cut violence-related emergency department
visits by 6,000 a year in England and Wales, say researchers.
PMID- 27484540
TI - Exercise as effective as surgery for common knee injury.
AB - Supervised exercise therapy should be considered as a treatment option for middle
aged patients with a common knee injury, say researchers.
PMID- 27484541
TI - Patients with sleep apnoea and resistant hypertension at increased risk of heart
disease.
AB - People with resistant hypertension are more likely to experience sleep apnoea
than those with nonresistant hypertension, increasing the risk of ischaemic heart
events and congestive heart failure, new study results suggests.
PMID- 27484543
TI - Computer model sheds light on amyloid plaque formation.
AB - Researchers from the University of Cambridge's department of chemistry have shown
that it may be possible to control the mechanism that leads to the rapid build-up
of amyloid plaques - a key hallmark of Alzheimer's disease.
PMID- 27484544
TI - Inside the fragile world of eating disorders.
AB - 'Take yourself back to the age of 15. What thoughts swirled around your head? Did
you worry about how you looked or what your friends and teachers thought of you?'
Wendy Clarke, specialist lead for eating disorders at Aneurin Bevan University
Health Board in South Wales, believes nurses should be asking themselves these
questions if they are to fully empathise, engage with and help young people with
eating disorders.
PMID- 27484545
TI - Gardening your way to health.
AB - A King's Fund report published in May found overwhelming evidence of the
beneficial effects of gardening on physical and mental wellbeing.
PMID- 27484546
TI - Revalidation is not a test.
AB - Much has been written about the steps necessary for nurses and midwives to comply
with revalidation. But what does it actually achieve?
PMID- 27484547
TI - Organise a learning event and see the benefits.
AB - The first step is to make managers aware of your intentions and get them on
board. They can advise you about the best time to have the event to ensure a good
turnout. If you have decided on a theme, make sure you line up a guest speaker
early. Your motto has to be 'fail to prepare, prepare to fail'.
PMID- 27484548
TI - Building bridges in an uncertain world.
AB - Three months into my new role at the International Council of Nurses (ICN), it is
clear that nursing is high on the agenda of big global institutions.
PMID- 27484549
TI - What needs to change.
AB - Earlier this year we heard how Southern Health NHS Foundation Trust had failed to
investigate the deaths of more than 1,000 patients with mental health problems.
It was a reminder to me of the importance of my work as a clinical adviser to the
Parliamentary and Health Service Ombudsman, the body that makes final decisions
on unresolved complaints about the NHS in England.
PMID- 27484550
TI - Getting over the bursary blues.
AB - The decision to scrap bursaries will discourage people from applying for degree
courses.
PMID- 27484551
TI - Specialist complex care.
AB - I agree with your editorial on how NHS England and the Department of Health (DH)
have failed to realise that specialist care for complex diseases requires
experienced and knowledgeable support.
PMID- 27484554
TI - District nursing is vital.
AB - Queen's Nursing Institute chief executive Crystal Oldman has welcomed the RCN
congress resolution urging RCN council to lobby for all district nurses to have a
specialist practice qualification. This provides the ideal route for future
talent and must be supported.
PMID- 27484555
TI - Correction.
AB - The CPD article Palliative and end of life care for people living with dementia
in care homes: part 2 (29 June 2016) wrongly referred to oxycodone as a 'mild'
opioid. Oxycodone is a controlled opioid for the management of high levels of
pain and care must be taken in its administration.
PMID- 27484556
TI - Readers' panel - Should personal use of illegal drugs be decriminalised?
AB - Our experts consider a hot topic of the day.
PMID- 27484557
TI - Learning can be a joy when others are willing to teach.
AB - 'He who is afraid of asking is ashamed of learning,' says a Danish proverb. I get
the drift, but I think 'he who is afraid of asking is being taught by the wrong
person' is nearer the mark.
PMID- 27484559
TI - Headspace - Guided Meditation and Mindfulness Techniques.
AB - Mindfulness has been recommended by the National Institute for Health and Care
Excellence and the NHS to help mental wellbeing, but can the Headspace app be
used by nurses and health professionals in clinical settings?
PMID- 27484561
TI - Student life - Twitter - a great medium for learning and debate.
AB - Twitter is ideal for nurses and nursing students to start a discussion and
debate, share innovative practice and, as lifelong learners, keep up to date with
evidence-based care. The social media platform is often the first place new ideas
and concepts are aired. Even if you don't tweet, it is likely you know about
campaigns that used Twitter to raise awareness, such as the late Kate Granger's
#hellomnynameis campaign. Tommy Whitelaw, a keynote speaker at this year's RCN
congress in Glasgow, tweets under @TommyNtour to raise awareness of dementia by
sharing his mother's story.
PMID- 27484562
TI - All patients deserve holistic care.
AB - Towards the end of my first year of training, I was on placement on a hospital
ward when I heard the alarm bell go off in a bathroom.
PMID- 27484563
TI - Learning how to promote effective communication.
AB - With the importance attached to freedom of speech, it is easy to take voicing
your thoughts for granted. But communication can be a challenge for many people.
PMID- 27484564
TI - 'You have to explain the risks and benefits'.
AB - Oncology trials nurse Juliah Jonasi became a clinical nurse researcher five years
ago, and has not looked back. 'I don't think I would want to do anything else
now,' she says.
PMID- 27484565
TI - 'I love the variety of the role'.
AB - Jason Warriner held senior NHS nursing positions before becoming clinical
director at the Terrence Higgins Trust. He was also a UK director of quality and
clinical services at Marie Stopes International, and chair of the RCN public
health nursing forum.
PMID- 27484566
TI - How to submit your revalidation application.
AB - Rationale and key points This is the final in a series of eight articles
providing information about the Nursing and Midwifery Council revalidation
process. This article focuses on submitting a revalidation application to the
NMC. " Nurses and midwives must demonstrate that they have: completed 450 hours
of practice, or 900 hours if revalidating as both a nurse and midwife; undertaken
35 hours of continuing professional development, 20 hours of which must be
participatory; recorded five examples of feedback on their practice; written five
reflective accounts; had a reflective discussion with an NMC registrant; and
sought confirmation that they have met these requirements. " Nurses and midwives
who fail to submit their revalidation application by the stated date will put the
renewal of their registration at risk. Reflective activity 'How to' revalidate
articles can help to update your practice and provide information about the
revalidation process, including how you can submit your revalidation application.
Reflect on and write a short account of: 1. The professional accountability
associated with declaring that you have met the revalidation requirements. 2. How
you could use this article to educate your colleagues. Subscribers can upload
their reflective accounts at: rcni.com/portfolio .
PMID- 27484567
TI - Assessment and accountability: part 3 - sign-off mentors.
AB - Assessment in clinical practice is a complex role undertaken by mentors and
practice teachers. This article is the third of three articles about assessment
in practice. Part one focused on the importance of assessment and identified
assessment methods used in clinical practice, while part two discussed the
importance of feedback and managing failing students. This article examines the
concepts of responsibility and accountability as well as ethical issues for
mentors and practice teachers in relation to the assessment process. The role of
the sign-off mentor, the issue of due regard, and ethical principles are
discussed. The meaning of competence and partnership working when making
assessment decisions are explored. This article relates to the third domain and
outcomes of the Nursing and Midwifery Council's Standards to Support Learning and
Assessment in Practice on assessment and accountability.
PMID- 27484568
TI - Assessment of injury severity in patients with major trauma.
AB - Major trauma centres provide specialised care for patients who have experienced
serious traumatic injury. This article provides information about major trauma
centres and outlines the assessment tools used in this setting. Since patients in
major trauma centres will be transferred to other settings, including inpatient
wards and primary care, this article is relevant for both nurses working in major
trauma centres and in these areas. Traumatic injuries require rapid assessment to
ensure the patient receives prompt, adequate and appropriate treatment. A range
of assessment tools are available to assist nurses in major trauma centres and
emergency care to assess the severity of a patient's injury. The most commonly
used tools are triage, Catastrophic Haemorrhage Airway to Exposure assessment,
pain assessment and the Glasgow Coma Scale. This article summarises the use of
these assessment tools in these settings, and discusses the use of the Injury
Severity Score (ISS) to determine the severity of patient injuries.
PMID- 27484569
TI - Nursing and Midwifery Council revalidation.
AB - What was the nature of the CPD activity and/or practice-related feedback and/or
event or experience in your practice? The CPD article discussed the Nursing and
Midwifery Council (NMC) revalidation process for nurses and midwives in the UK.
It outlined the requirements for revalidation that every nurse and midwife in the
UK must meet to remain on the NMC register.
PMID- 27484570
TI - 'I could not have survived without Kelly and her team'.
AB - With her team of unsung heroes at Sandwell General Hospital in the West Midlands,
Kelly carries out sterling work in the aftercare of patients with bowel cancer,
rectal cancer and other debilitating aspects of incontinence.
PMID- 27484571
TI - Appropriate care for people with learning disabilities.
AB - How can nurses meet the healthcare needs of people with learning disabilities in
the community? Solutions include addressing communication difficulties and issues
of consent, and developing professionals' education.
PMID- 27484572
TI - Telehealth brings benefits.
AB - A telehealth clinical lead writing in Primary Health Care says that for the NHS
to thrive, front line staff and patients must be empowered. New ways of working
are needed and the use of technology should be maximised. Telehealth allows
nurses to work more efficiently, communicate better with patients and families,
and improve health outcomes cost-effectively. The author encourages frontline
nurses to implement changes in the work place and suggests NHS Change Day in
October as a starting point. The article also notes the importance of social
media in opening up opportunities to connect with other nurses.
PMID- 27484573
TI - Big picture.
AB - 'Higher doses of radiotherapy could result in prostate cancer patients undergoing
treatment in half of the time'.
PMID- 27484574
TI - Developing a career in nursing research.
AB - What is the best way to build a career in nursing research? In Nurse Researcher
Michelle Cleary and colleagues provide an overview of the career essentials for
nurses at the beginning careers as researchers. They discusses collaborations,
research support, grants, supervising students and climbing the research career
ladder.
PMID- 27484575
TI - Online.
AB - 'I recently found myself on a placement with limited learning opportunities,
which I found exasperating. Yet it is important to reflect on our experiences,
even the bad ones. There is always a lesson to learn, however small'.
PMID- 27484576
TI - Post hoc analysis of the glutamics-trial: intravenous glutamate infusion and use
of inotropic drugs after cabg.
AB - BACKGROUND: Intravenous glutamate reduced the risk of developing severe
circulatory failure after isolated coronary artery bypass graft surgery (CABG)
for acute coronary syndrome (ACS) in a double-blind randomised clinical trial
(GLUTAMICS-ClinicalTrials.gov Identifier: NCT00489827 ). Here our aim was to
study if glutamate was associated with reduced the use of inotropes. METHODS:
Post-hoc analysis of 824 patients undergoing isolated CABG for ACS in the
GLUTAMICS-trial. ICU-records were retrospectively scrutinised including hourly
registration of inotropic drug infusion, dosage and total duration during the
operation and postoperatively. RESULTS: ICU-records were found for 171 out of 177
patients who received inotropes perioperatively. Only one fourth of the patients
treated with inotropes fulfilled study criteria for postoperative heart failure
at weaning from cardiopulmonary bypass (CPB) or later in the ICU. Inotropes were
mainly given preemptively to facilitate weaning from CPB or to treat
postoperative circulatory instability (bleeding, hypovolaemia). Except for a
significantly lower use of epinephrine there were only trends towards lower need
of other inotropes overall in the glutamate group. In patients treated with
inotropes (glutamate n = 17; placebo n = 13) who fulfilled study criteria for
left ventricular failure at weaning from CPB the average duration of inotropic
treatment (34 +/- 20 v 80 +/- 77 h; p = 0.014) and the number of inotropes used
(1.35 +/- 0.6 v 1.85 +/- 0.7; p = 0.047) were lower in the glutamate group.
CONCLUSIONS: Intravenous glutamate was associated with a minor influence on
inotrope use overall in patients undergoing CABG for ACS whereas a considerable
and significant reduction was observed in patients with heart failure at weaning
from CPB.
PMID- 27484577
TI - Cryopreservation of Peruvian Paso horse spermatozoa: dimethylacetamide preserved
an optimal sperm function compared to dimethyl sulfoxide, ethylene glycol and
glycerol.
AB - The objective was to evaluate the effect of different cryoprotectant agents in
the cryopreservation of Peruvian Paso horse semen. Twenty semen samples were
collected from five Peruvian Paso horse stallions. Each sample was divided into
12 parts to form the groups: dimethylacetamide (DMA), dimethyl sulfoxide (DMSO),
ethylene glycol (EG) and glycerol (GLY), at 3%, 4% and 5%. Samples were frozen
using a rate-controlled freezer. Sperm parameters evaluated were motility and
viability/acrosomal status. After thawing, progressive motility in DMA group was
higher (p < .05) than in DMSO, EG and GLY groups. Similarly, viable acrosome
intact spermatozoa were higher (p < .05) using DMA in comparison with DMSO. No
differences were found when comparing concentrations for any of the
cryoprotectant agents. In conclusion, DMA seems to be a good cryoprotectant agent
for the cryopreservation of Peruvian Paso horse stallion semen.
PMID- 27484578
TI - Diverse modes of NMDA receptor positive allosteric modulation: Mechanisms and
consequences.
AB - NMDA Receptors (NMDARs) play key roles in synaptic physiology and NMDAR
hypofunction has been implicated in various neurological conditions. In recent
years an increasing number of positive allosteric modulators (PAMs) of NMDARs
have been discovered and characterized. These diverse PAM classes vary not only
in their binding sites and GluN2 subunit selectivity profiles, but also in the
nature of their impacts on channel function. Major differences exist in the
degree of slowing of channel deactivation and shifting of apparent agonist
affinity between different classes of PAMs. Here we review the diverse modes of
potentiation by the currently known classes of NMDAR PAMs and discuss the
potential consequences of different types of potentiation in terms of desirable
and undesirable effects on brain function. This article is part of the Special
Issue entitled 'Ionotropic glutamate receptors'.
PMID- 27484579
TI - Preferential Nucleation during Polymorphic Transformations.
AB - Polymorphism is the ability of a solid material to exist in more than one phase
or crystal structure. Polymorphism may occur in metals, alloys, ceramics,
minerals, polymers, and pharmaceutical substances. Unresolved are the conditions
for preferential nucleation during polymorphic transformations in which
structural relationships or special crystallographic orientation relationships
(OR's) form between the nucleus and surrounding matrix grains. We measured in
situ and simultaneously the nucleation rates of grains that have zero, one, two,
three and four special OR's with the surrounding parent grains. These experiments
show a trend in which the activation energy for nucleation becomes smaller - and
therefore nucleation more probable - with increasing number of special OR's.
These insights contribute to steering the processing of polymorphic materials
with tailored properties, since preferential nucleation affects which crystal
structure forms, the average grain size and texture of the material, and thereby
to a large extent - the final properties of the material.
PMID- 27484580
TI - Race and General Strain Theory: Examining the Impact of Racial Discrimination and
Fear on Adolescent Marijuana and Alcohol Use.
AB - BACKGROUND: To extend our knowledge of general strain theory by exploring how
under-researched strains such as racial discrimination, witnessing violence,
physical victimization and verbal bullying affect adolescent substance use while
considering differences according to racial identification. METHODS: This
research utilized data from wave three of the Project on Human Development in
Chicago Neighborhoods. Statistical analysis was primarily composed of path
analysis using full information maximum likelihood parameter estimates. RESULTS:
The findings reveal that reporting fear decreased alcohol and marijuana use among
adolescents and that racial discrimination, witnessing violence, and being the
victim of verbal bullying indirectly affected marijuana and alcohol use through
fear. No support was found for depression as a mediating variable. Physical
victimization was the only social strain that had a direct positive effect on
marijuana and alcohol use but only for Hispanics and African Americans.
CONCLUSIONS: The results suggest that strains may be operating differently and
there may be differential levels of exposure to certain strains according to
one's race.
PMID- 27484582
TI - Elucidating the effects of pH shift on IgG1 monoclonal antibody acidic charge
variant levels in Chinese hamster ovary cell cultures.
AB - Charge variants, especially acidic charge variants, in recombinant monoclonal
antibodies are critical quality attributes, which can affect antibodies'
properties in vitro and in vivo. Meanwhile, charge variants are cumulative
effects of various post-translational modifications and chemical degradations on
antibody. In this work, to investigate the effect of lowering culture pH in the
stationary phase on acidic charge variant contents in fed-batch cultures and its
mechanism, cell culture experiments in 2-L bioreactors were firstly performed to
explore the changes in the charge distribution under the pH downshift condition
using weak cation exchange chromatography. It is found that acidic charge variant
contents were significantly decreased by pH downshift. Then, to reveal the
mechanism by which the content of acidic charge variants is reduced under pH
downshift condition, the variation of post-translational modifications and
chemical degradations under the pH downshift condition was explored. Meanwhile,
the structure of the acidic charge variants was characterized. Several analysis
experiments including size exclusion chromatography, capillary electrophoresis
sodium dodecyl sulfate under non-reducing conditions, tryptic peptide map, and
reduced antibody mass were applied in this study. The results show that the
mechanism by which the content of acidic charge variants is reduced is that the
contents of disulfide bond reduction, galactosylation, and asparagine deamination
of the HC-N388 in the Fc domain were reduced by pH downshift.
PMID- 27484581
TI - Solar-Driven H2 O2 Generation From H2 O and O2 Using Earth-Abundant Mixed-Metal
Oxide@Carbon Nitride Photocatalysts.
AB - Light-driven generation of H2 O2 only from water and molecular oxygen could be an
ideal pathway for clean production of solar fuels. In this work, a mixed metal
oxide/graphitic-C3 N4 (MMO@C3 N4 ) composite was synthesized as a dual-functional
photocatalyst for both water oxidation and oxygen reduction to generate H2 O2 .
The MMO was derived from a NiFe-layered double hydroxide (LDH) precursor for
obtaining a high dispersion of metal oxides on the surface of the C3 N4 matrix.
The C3 N4 is in the graphitic phase and the main crystalline phase in MMO is
cubic NiO. The XPS analyses revealed the doping of Fe(3+) in the dominant NiO
phase and the existence of surface defects in the C3 N4 matrix. The formation and
decomposition kinetics of H2 O2 on the MMO@C3 N4 and the control samples,
including bare MMO, C3 N4 matrix, Ni- or Fe-loaded C3 N4 and a simple mixture of
MMO and C3 N4 , were investigated. The MMO@C3 N4 composite produced 63 MUmol L(
1) of H2 O2 in 90 min in acidic solution (pH 3) and exhibited a significantly
higher rate of production for H2 O2 relative to the control samples. The positive
shift of the valence band in the composite and the enhanced water oxidation
catalysis by incorporating the MMO improved the light-induced hole collection
relative to the bare C3 N4 and resulted in the enhanced H2 O2 formation. The
positively shifted conduction band in the composite also improved the selectivity
of the two-electron reduction of molecular oxygen to H2 O2 .
PMID- 27484583
TI - Chaperone-assisted expression of KfiC glucuronyltransferase from Escherichia coli
K5 leads to heparosan production in Escherichia coli BL21 in absence of the
stabilisator KfiB.
AB - The heparosan synthase of Escherichia coli K5 is composed of the
glycosyltransferases KfiA and KfiC which synthesize the polysaccharide heparosan
(N-acetylheparosan). A third protein, KfiB, is required to stabilize the KfiAC
complex in the bacteria and to transport this complex to the inner membrane where
the initiation of polymerization occurs. In this report, we fused KfiC with the
E. coli trigger factor (TF) to stabilize KfiC, thus activating the enzyme in the
absence of KfiB. Different recombinant plasmids were constructed to compare the
impact of the presence or absence of KfiB and the presence of the trigger factor
as a fusion protein. Several E. coli BL21-derived strains were transformed with
recombinant plasmids and cultivated in fed-batch conditions on minimal medium.
The bTCA strain overexpressing fused TF-KfiC together with KfiA and KfiD, but
lacking KfiB produced 1.5 g/L of total heparosan after 24 h of fed-batch
cultivation. This heparosan was essentially intracellular early in the culture,
providing evidence that KfiB primarily plays a role in the exportation process.
However, over time, heparosan became mostly extracellular, likely due to passive
diffusion or partial cell disruption upon product accumulation.
PMID- 27484584
TI - High Mobility Group A proteins in esophageal carcinomas.
AB - We have recently shown that HMGA2 is overexpressed in esophageal squamous cell
carcinoma (ESCC) and its detection allows to discriminate between cancer and
normal surrounding tissue proposing HMGA2 as a novel diagnostic marker.
Interestingly, esophageal adenocarcinoma shows an opposite behavior with the
overexpression of HMGA1 but not HMGA2. Moreover, we show that the suppression of
HMGA2 in 2 ESCC cell lines reduces the malignant phenotype. Then, this paper
highlights a differential induction of the HMGA proteins, depending on the cancer
histological type, and reinforces the perspective of an innovative esophageal
cancer therapy based on the suppression of the HMGA protein function and/or
expression.
PMID- 27484585
TI - Factors that can alter the melatonin circadian rhythm.
PMID- 27484586
TI - The effect of PAMAM dendrimer concentration, generation size and surface
functional group on the aqueous solubility of candesartan cilexetil.
AB - This article investigates the aqueous solubility of the poorly soluble drug
candesartan cilexetil (CC) in the presence of poly(amidoamine) (PAMAM)
dendrimers. The effect of variables such as concentration, generation size (G2
G4), and surface groups (NH2, COOH and TRIS) of PAMAMs on the aqueous solubility
of CC was studied. A two-factor factorial (3 * 3) ANOVA design was used to study
the effect of generation size and surface functional group of the PAMAMs. The
results showed that the aqueous solubility of CC in the presence of carboxyl and
TRIS-terminated PAMAMs was higher than those of amine-terminated PAMAMs, and the
effect of surface functional group of the PAMAMs on the aqueous solubility of CC
was dependent on the generation size (p < 0.05). The sequence of the observed
solubility fold enhancement due to PAMAMs was G4.COOH (8378)>G3.COOH
(3456)>G4.TRIS (2362)>G2.COOH (1013)>G3.TRIS (749)>G2.TRIS (293)>G4.NH2
(91)>G3.NH2 (50)>G2.NH2 (37). The CC-PAMAM dendrimer inclusion complexes were
characterized by UV-Vis, attenuated total reflectance-Fourier transform infrared
spectroscopy (ATR-FTIR) and differential thermal analysis (DTA) techniques.
Regarding the results of these techniques, improvement in the solubility of CC is
expected primarily through the intermolecular hydrogen bonding between the drug
and internal tertiary and surface functional groups of the studied PAMAMs.
PMID- 27484587
TI - Optimization of Reference Genes for Normalization of Reverse Transcription
Quantitative Real-Time Polymerase Chain Reaction Results in Senescence Study of
Mesenchymal Stem Cells.
AB - Recently, it has been suggested that cellular senescence is associated with stem
cell exhaustion, which reduces the regenerative potential of tissues and
contributes to aging and age-related diseases. Mesenchymal stem cells (MSCs)
attract a large amount of attention in stem cell research and regeneration
medicine because they possess multiple advantages and senescent MSCs could be one
of the most useful stem cell models in aging studies. It is important to
quantitatively evaluate senescence markers to both identify and study the
mechanisms involved in MSC senescence. Reverse transcription quantitative real
time polymerase chain reaction (RT-qPCR) is currently the most widely used tool
to quantify the mRNA levels of markers. However, no report has demonstrated the
optimal reference genes that should be used to normalize RT-qPCR in senescence
studies of MSCs. In this study, we compared 16 commonly used reference genes
(GAPDH, ACTB, RPL13A, TBP, B2M, GUSB, RPLPO, YWHAZ, RPS18, EEF1A1, ATP5F1, HPRT1,
PGK1, TFRC, UBC, and PPIA) in proliferating or replicative-senescent human
adipose-derived MSCs (hAD-MSCs) that were isolated from seven healthy donors aged
29-59 years old. Three algorithms (geNorm, NormFinder, and BestKeeper) were used
to determine the most optimal reference gene. The results showed that PPIA
exhibited the most stable expression during senescence, while the widely used
ACTB exhibited the lowest stability. We also confirmed that different reference
genes lead to different evaluations of senescence markers. Our work ensures that
results obtained from senescence studies of hAD-MSCs will be appropriately
evaluated in both basic research and clinical trials.
PMID- 27484588
TI - X-chromosome gene dosage as a determinant of impaired pre and postnatal growth
and adult height in Turner syndrome.
PMID- 27484589
TI - Astaxanthin blocks preeclampsia progression by suppressing oxidative stress and
inflammation.
AB - To investigate the antioxidative effect of astaxanthin on Nomega-nitro-L-arginine
methyl ester (L-NAME)-induced preeclamptic rats. Cell survival, the level of
reactive oxygen species (ROS) and the changes in mitochondrial membrane potential
(MMP) were examined in astaxanthin and H2O2-treated human umbilical vein
endothelial cells (HUVECs). The preeclamptic Sprague-Dawley (SD) rat model was
established by injection of L-NAME and treatment with astaxanthin. The activities
of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide synthase
(NOS) in serum were analyzed. Pathological changes were examined by hematoxylin
and eosin (H&E) staining. The expression of nuclear factor (NF)-kappaB, Rho
associated protein kinase II (ROCK II), heme oxygenase-1 (HO-1) and caspase 3 in
preeclamptic placentas were examined by immunohistochemistry. Astaxanthin
significantly reduced H2O2-induced HUVEC cell death, decreased ROS and increased
MMP. Astaxanthin significantly reduced blood pressure and the content of MDA, but
significantly increased the activity of SOD in preeclamptic rats. The urinary
protein and the level of NO and NOS were also decreased. H&E staining revealed
that the thickness of the basilar membrane was increased, while the content of
trophoblast cells and spiral arteries were reduced following astaxanthin
treatment. Immunohistochemistry results showed that the expression of NF-kappaB,
ROCK II and caspase 3 in preeclamptic placentas was significantly decreased after
astaxanthin treatment, while HO-1 expression was increased. In conclusion,
astaxanthin inhibited H2O2-induced oxidative stress in HUVECs. Astaxanthin
treatment significantly improved L-NAME-induced preeclamptic symptoms and reduced
the oxidative stress and inflammatory damages in preeclamptic placentas.
Astaxanthin treatment may effectively prevent and treat preeclampsia.
PMID- 27484591
TI - Regiodivergent Ring-Opening Reaction of Trichloromethylcyclopropane Carboxylates.
AB - Reagent-controlled regiodivergent ring-opening reactions of
trichloromethylcyclopropane carboxylates have been developed. The
regioselectivity of bond cleavage is completely controlled by the proper choice
of silver salts; the treatment of trichloromethylcyclopropane with AgBF4 led to
C2-C3 bond cleavage and fluorination to afford fluorinated beta,gamma-unsaturated
ester with high stereoselectivity, while the reaction with AgOAc in THF gave a
gamma,delta-unsaturated ester through the reductive cleavage of the C1-C2 bond.
PMID- 27484590
TI - Eating, feeding, and feeling: emotional responsiveness mediates longitudinal
associations between maternal binge eating, feeding practices, and child weight.
AB - BACKGROUND: Although it is known that maternal disordered eating is related to
restrictive feeding practices, there is little research exploring mechanisms for
this association or its effects on other feeding practices. The purpose of this
study was to assess whether maternal emotion responses mediate the association
between maternal binge eating (BE) and child feeding practices, in order to
identify potential risk factors for feeding practices that influence child
weight. METHODS: This longitudinal observational study included (n = 260) mothers
and children from the STRONG Kids Panel Survey. At Wave 1, children were an
average of 37 months old (SD = 6.9), and at Wave 2 children were an average of 57
months old (SD = 8.3). Mothers self-reported their frequency of binge eating
behavior (Wave 1), responses to children's negative emotions (Wave 1), feeding
practices (Wave 1 and Wave 2), and child height and weight were measured at both
time points. Using bias-corrected bootstrapping procedures, we tested the
hypothesis that longitudinal associations between maternal BE and nonresponsive
parent feeding practices would be mediated by parents' unsupportive responses to
children's negative emotion. We also tested a serial mediation model positing
that maternal BE predicts child body mass index (BMI) percentile change 18-24
months later, indirectly through unsupportive responses to negative emotion and
nonresponsive feeding practices. RESULTS: Maternal BE predicted use of more
nonresponsive feeding practices (e.g. Emotion Regulation, Restriction for Health,
Pressure to Eat, and Food as Reward), indirectly through more Distress responses
to children's negative emotions. In the serial mediation model, maternal BE was
associated with greater use of Distress responses, which indirectly predicted
higher child BMI percentile through Food as Reward feeding practices.
CONCLUSIONS: These results suggest that maternal eating and emotion
responsiveness are important for understanding the interpersonal context of
feeding behaviors, and child weight outcomes. Distress responses may serve as a
risk factor for use of unhealthful feeding practices among mothers with BE and
these responses may increase children's risk for weight gain. TRIAL REGISTRATION:
This study used an observational prospective design. Therefore, it has not been
registered as a clinical intervention trial.
PMID- 27484592
TI - Onco-Golgi: The Missed Target.
AB - The Golgi apparatus or complex, a highly dynamic organelle, is a factory in which
proteins are processed and sorted for transport to various target organelles.(1)
It was first discovered by Camillo Golgi in 1898 and was described as an
intracellular reticular apparatus stained by the 'black reaction' in neuronal
cells.(1,2) Despite of several research works, this complex remains one of the
most inexplicable structures of the cytoplasmic organelles.
PMID- 27484593
TI - Prophylactic and Therapeutic Antibiotic Patterns of Lebanese Dentists for the
Management of Dentoalveolar Abscesses.
AB - INTRODUCTION: General dentists issue approximately 10% of antibiotic
prescriptions across the global medical community consummation. The use of
antibiotics for the management of dentoalveolar infections should be considered
only in the presence of an increased risk of a systemic involvement or to prevent
metastatic infections. This study aimed to investigate the prophylactic and
therapeutic antibiotic prescription patterns of Lebanese dentists for the
management of dentoalveolar abscesses. The aim was to evaluate the influence of
the patients' medical condition and clinical signs data on the patterns of
antibiotics prescription. MATERIALS AND METHODS: Only patients with a
dentoalveolar abscess were included in the study. Age, medical history, reason
for consultation, clinical signs and symptoms, diagnosis, type of local
treatment, and type of antibiotherapy were collected for each patient attending
dental clinics in Beirut. The data were analyzed with chi-square test and
multivariate regression. RESULTS: Out of the 563 initial patients, 127 were
selected for the study and received a local treatment. The patient's medical
condition and age did not affect the decision to prescribe antibiotics 36.2%
patients with pain and 11.8% patients with swelling were prescribed antibiotics.
Pain and swelling contributed to a higher level of antibiotic prescription
compared to other signs and symptoms. Antibiotics were prescribed inappropriately
to 51.76 and 38.10% among patients with an acute or chronic dentoalveolar abscess
respectively. The main prescribed antibiotic was amoxicillin. CONCLUSION: This
study showed that dentists often did not follow the current prophylactic and
therapeutic antibiotic prescription guidelines. CLINICAL SIGNIFICANCE:
Antibiotics prescriptions in dentistry will be more pertinent, leading to a
decrease in inadequacy of prescriptions, microbial resistance, and the
development of multiresistant germs against antibiotics.
PMID- 27484594
TI - Assessment of Dental Arch Changes and Buccal Bone Thickness in Patients treated
with Self-ligating Brackets.
AB - AIMS: To evaluate changes in transverse dimensions of upper arch and thickness of
the buccal bone plate in patients undergoing orthodontic treatment during the
leveling phase. MATERIALS AND METHODS: Sixteen patients aged between 11 and 30
years, presenting with class I and II malocclusion, with minimum of 2 mm crowding
treated without extraction, were divided into two groups: GI (n = 8), self
ligating brackets (Easyclip Aditek), and GII (n = 8), conventional preadjusted
brackets (3M Unitek). The intercanines, interpremolar, and intermolar widths were
measured in dental casts using a digital caliper, before (T1) and after 6 months
of treatment (T2). Measurements of the thickness of the bone plate were performed
by using cone-beam computed tomography (CBCT) scans and Dolphin three-dimensional
program. Paired and nonpaired t tests were applied to analyze the results in and
between the groups for the changes in the transversal arch dimensions and buccal
bone thickness. RESULTS: In all statistical tests, the significance level was set
at 5%. A nonsignificant increase in transverse dimensions and a slight reduction
on thickness of the buccal bone plate were observed in both groups. CONCLUSION:
The dimensional changes of transverse and thickness of the bone plate during the
initial phase of treatment were similar, regardless of the bracket design.
CLINICAL SIGNIFICANCE: It should be noted that the bracket design does not
influence the treatment course regarding transversal dimensions and buccal bone
thickness.
PMID- 27484595
TI - Evaluation of Gingival Health Status among 6- and 12-years-old Children in Dhamar
City, Yemen: A Cross-sectional Study.
AB - INTRODUCTION: Epidemiological data on gingivitis in children are important for
understanding the natural course of the disease, identifying its risk factors,
and predicting its time trends. The objective of this study was to evaluate the
prevalence and severity of gingivitis among 6- and 12-year-old school children in
Dhamar city, Yemen. MATERIALS AND METHODS: A total of 663 children (310 children
of 6 years old and 353 children of 12 years old) were examined from 10 public
primary schools. Gingival health status was assessed using the plaque index (PI),
calculus index (CI), and gingival index (GI) on the six Ramfjord teeth. The
latter index was used to categorize gingivitis severity at the subject level.
Data were analyzed using independent f-test, chi-squared test, and Spearman's
correlation. A p-value of < 0.05 was considered significant. RESULTS: Both age
groups had high mean of PI and GI with nonsignificant difference. The 12-year-old
children had calculus deposits much higher than the 6-year-old group with
significant difference. There was a significant correlation between age and
gender of the whole sample with CI [(odds ratio, OR = 1.65, p = 0.003) and (OR =
0.74, p = 0.05) respectively]. Most of the participants presented with gingival
inflammation, which was less in 12-year-old females. CONCLUSION: Poor oral
hygiene and mild gingivitis were highly prevalent among Yemeni school children.
CLINICAL SIGNIFICANCE: The early assessment and intervention of gingivitis and
periodontitis will minimize the chance of tooth loss. It has been reported that
marginal gingivitis begins early in childhood, increases in prevalence and
severity at puberty, and then subsides slightly to the remainder of the second
decade of life.
PMID- 27484596
TI - An Evaluation of GuttaFlow2 in Filling Artificial Internal Resorption Cavities:
An in vitro Study.
AB - INTRODUCTION: Obturation of root canal with internal resorption represents a
major challenge in Endodontics. In spite of that, usual obturation techniques are
often employed without considering the best technique to solve this problem. The
goal of this study was to investigate the ability of GuttaFlow2 in filling
artificial internal resorption cavities. MATERIALS AND METHODS: The study sample
included 36 human upper central incisors that were prepared using Protaper system
(F4). Internal resorption cavities were prepared by cutting each tooth at 7 mm
from the apex and preparing hemispherical cavities on both the sides and then re
attaching them. The sample was randomly separated into three groups (n = 12 in
each group). In the first group, thermal injection technique (Obtura II) was
employed and served as the control group. In the second group, injection of cold
free-flow obturation technique with a master cone (GF2-C) was employed, whereas
in the third group injection of cold free-flow obturation without a master cone
(GF2) was followed. The teeth were re-cut at the same level as before and
examined under a stereomicroscope. Subsequently, the captured images were
transferred to AutoCAD program to measure the percentage of total filling "TF,"
gutta-percha "G," sealer "S," and voids "V" out of the total surface of the cross
sections. RESULTS: All materials showed high filling properties in terms of
"total filling," ranging from 99.17% (for Obtura II) to 99.72% (for GF2-C).
Regarding gutta-percha percentages of filling, they ranged from 83.15 to 83.93%,
whereas those for the sealer ranged from 5.71 to 15.24%. GuttaFlow2 group with a
master cone appeared to give the best results despite the insignificant
differences among the three groups. CONCLUSION: The GuttaFlow2 with a master cone
technique seemed to be a promising filling material and gave results similar to
those observed with Obtura II. It is recommended for use to obturate internal
resorption cavities in clinical practice due to its good adaptability to root
canal walls, ease of handling, and application. CLINICAL SIGNIFICANCE: Internal
resorption defects can be successfully filled with GuttaFlow2 material when
supplemented with a master cone, and the results are comparable with those
obtained with the Obtura II technique.
PMID- 27484597
TI - Assessment of the Influence of Meal Type on Fluoride Absorption due to Ingestion
of professionally Applied Gels.
AB - AIMS: The aim of this study is to assess the influence of eating, prior to
application of professionally used gels, on the rate of fluoride absorption due
to the ingestion of 1.23% acidulated phosphate fluoride (APF). MATERIALS AND
METHODS: After fasting for 12 hours, 16 adult volunteers (> 65 kg) ingested two
types of meal: Breakfast (n = 8) and Lunch (n = 8). Accidental ingestion of
fluoride gel used in molding trays was simulated (12,300 ppm; 61.5 mg F; pH =
4.65) 15 minutes after eating. After ingestion of the fluoride solution, 3 mL of
venous blood were collected at the following times: Zero (before ingestion) and
15, 30, 45 minutes, 1, 2, and 3 hours. Fluoride concentrations in blood plasma
were determined using an ion selective electrode. RESULTS: With the exception of
time 0 (p > 0.05), the average blood plasma concentration of the breakfast group
(BG) (0.34 +/- 0.04 mg/L) was higher than that of the lunch group (LG) (0.24 +/-
0.03 mg/L), with the moment of peak concentration being 2 hours after ingestion
for both groups (BG = 0.4 mg/L; LG = 0.28 mg/L). CONCLUSION: Results reinforce
the idea that eating before undergoing professional application of fluoride is a
factor of extreme importance regarding its safety, and that the time following a
patient's heaviest meal should be the time of choice for planning clinical care.
CLINICAL SIGNIFICANCE: Our results should be considered when planning collective
action that involves the application of the gel on children in a school
environment, thus ensuring the procedure's safety.
PMID- 27484598
TI - In vitro Analysis of Cytotoxicity of Temporary Resilient Relining Materials.
AB - AIMS: The aim of this study is to evaluate the in vitro response of human
gingival fibroblasts in primary cultures to two materials for temporary relining
of dentures: Temporary Soft (TDV, Brazil) and Trusoft (Bosworth, USA) for 24
hours, 7 and 30 days by using a multi-parametric analysis. MATERIALS AND METHODS:
Each material sample (TDV, TS, Polystyrene, Latex) was prepared and incubated in
a culture medium for 1, 7, and 30 days at 37 degrees C. Human gingival
fibroblasts were exposed to the extracts and cell viability was evaluated by a
multi-parametric assay, which allowed sequential analysis of mitochondrial
activity (XTT), membrane integrity [neutral red (NR)], and cell density [crystal
violet dye exclusion (CVDE)] in the same cells. Analysis of variance (ANOVA) was
used to test the interactions of the three sources of variation (material, test
method, and time) with the proportions of viable cells for each relining
material. RESULTS: Both evaluated materials (TDV and TS) had low cytotoxic
effects during 1, 7, and 30 days after manipulation of the material, as assessed
by all three methods used. A statistical difference was found when comparing the
negative control group (latex fragments) with the other groups, which showed high
toxicity and low percentage of cell viability in all tests used. There was no
significant difference among other materials (p > 0.05). CONCLUSION: Low
cytotoxicity levels were detected by representatives of the major groups of
temporary prosthetic relining materials, as evaluated by multiple cellular
viability parameters in human fibroblasts. CLINICAL SIGNIFICANCE: There are
various soft materials on the market for relining prostheses; however, the
effects of these materials on tissues need to be clarified to avoid problems for
patients.
PMID- 27484599
TI - Functional Evaluation of the Behavior of Masticatory Muscles in
Zygomaticomaxillary Complex Fracture: A Prospective Study.
AB - AIMS: The purpose of this study is to functionally evaluate the behavior of the
masticatory muscles (masseter and temporalis) following zygomaticomaxillary
complex (ZMC) fractures by assessing bite force, electromyography (EMG), and
mandibular movements. MATERIALS AND METHODS: Group I consisted of 20 patients
with unilateral ZMC fractures who were treated surgically with one-, two-, or
three-point fixations at the frontozygomatic, infraorbital, or
zygomaticomaxillary buttress region as per clinical and radiological assessments.
Group II control group included 20 normal patients. The muscle activity was
functionally evaluated before and after the surgery for a period of 6 months. The
evaluation consisted of bite force measurement, EMG analysis of masseter and
temporalis muscles, and measurements of mandibular movements. RESULTS: There was
an increase in bite force and EMG activity throughout the evaluated postoperative
period, but at the end of 6 months, the values were still below the control
levels for majority of the patients. Maximum mouth opening increased considerably
after the surgery. CONCLUSION: According to bite force and EMG, the masticatory
musculature returned to near normal levels by the 3rd month after the surgery.
CLINICAL SIGNIFICANCE: Management of fractures of the zygoma by open reduction
and fixation raises the question of the location of fixation points owing to the
action of masseter and temporalis on the ZMC. This study supports the current
clinical concept of minimized fixation in treating ZMC fractures.
PMID- 27484600
TI - Assessment of Patients Referred to Specialty Dental Hospitals for Dental Implant
Procedure: A Retrospective Cohort Analysis.
AB - INTRODUCTION: One of the most common and effective ways of replacing missing
teeth is by dental implants. Both quality and quantity of bone along with the
area of implant placement govern the prognosis of the implant procedure. Certain
risk factors predispose the implant treatment to high failure rate. Hence, we
assessed the implant patients who were referred from private practitioners to the
specialty hospitals from 2010 to 2014. MATERIALS AND METHODS: All the patients
being referred from private clinics to the specialty dental hospital for the
purpose of prosthetic rehabilitation by dental implants from June 2010 to July
2014 were included in the present study. Skilled oral and maxillofacial surgeons
were appointed for performing the implant surgical procedures. Prosthetic
rehabilitation was done after 6 to 8 weeks and after 10 to 14 weeks in implant
cases without and with bone augmentation procedures respectively. Distribution of
dental implants based on the indications, location, dimension of augmentation
procedure, and complication of implants was analyzed and assessed for the level
of significance. RESULTS: Of the patients, 712 were females, while the remaining
were males. Most of the patients were in the age group of 50 to 59 years. As
compared with completely edentulous patients, most of the patients required
rehabilitation by a single implant. Maximum dental implants were placed in
maxillary premolar region and mandibular first molar region. Over 1,000 cases in
this study required rehabilitation by augmentation procedure. CONCLUSION:
Partially edentulous patients are most commonly referred to specialized dental
hospitals for prosthetic rehabilitation by dental implants, mostly with the
purpose of implant placement. Failure rate can be minimized by following strict
patient selection protocols along with following a standard surgical criterion.
CLINICAL SIGNIFICANCE: Following standard surgical protocols and strict treatment
planning, prognosis of the dental implant procedures can be improved to a greater
extent, thereby increasing its clinical success rate.
PMID- 27484601
TI - Assessment of Oral Status in Pediatric Patients with Special Health Care Needs
receiving Dental Rehabilitation Procedures under General Anesthesia: A
Retrospective Analysis.
AB - INTRODUCTION: Dental problems serve as additional burden on the children with
special health care needs (CSHCN) because of additional hospitalization pressure,
they face for the treatment of various serious medical problems. These patients
have higher incidence of dental caries due to increased quantity of sugar
involved in the drug therapies and lower salivary flow in the oral cavity. Such
patients are difficult to treat with local anesthesia or inhaled sedatives.
Single-sitting dental treatment is possible in these patients with general
anesthesia. Therefore, we conducted this retrospective analysis of oral health
status of CSHCN receiving various dental treatments in a given population.
MATERIALS AND METHODS: A total of 200 CSHCN of age 14 years or less reporting in
the pediatric wing of the general hospital from 2005 to 2014 that underwent
comprehensive dental treatment under general anesthesia were included in the
study. Patients with history of any additional systemic illness, any malignancy,
any known drug allergy, or previous history of any dental treatment were excluded
from the study. Complete mouth rehabilitation was done in these patients under
general anesthesia following standard protocols. Data regarding the patient's
disability, type, duration, and severity of disability was collected and
analyzed. All the results were analyzed by Statistical Package for the Social
Sciences (SPSS) software. Chi-square test, Student's t-test, and one-way analysis
of variance were used to assess the level of significance. RESULTS: Statistically
significant results were obtained while analyzing the subject's decayed missing
filled/decayed extracted filled teeth indices divided based on age. Significant
difference was observed only in cases where patients underwent complete crown
placement even when divided based on type of disability. While analyzing the
prevalence, statistically significant results were observed in patients when
divided based on their age. CONCLUSION: In CSHCN, dental pathologies and caries
indices are increased regardless of the type or extent of disability. CLINICAL
SIGNIFICANCE: Children with special health care needs should be given special
oral health care, and regular dental checkup should be conducted as they are more
prone to have dental problems.
PMID- 27484602
TI - Comparative Evaluation of C-reactive Proteins in Pregnant Women with and without
Periodontal Pathologies: A Prospective Cohort Analysis.
AB - INTRODUCTION: Inflammation of tooth supporting structures is referred to as
periodontitis. C-reactive proteins (CRP) levels are usually increased in case of
chronic inflammatory process like periodontitis. Association of CRP with
pregnancy has been observed in the past, which includes most commonly preterm
delivery, preeclampsia, etc. Therefore, it can be hypothesized that CRP may act
as a link between periodontitis and adverse pregnancy outcomes. Hence, we aim to
evaluate the plasma CRP levels in pregnant women with and without periodontal
pathologies. MATERIALS AND METHODS: The study included 210 pregnant women who
reported to the hospital with periodontal problems and for routine checkups. All
the patients were divided into three groups based on the presence and absence of
periodontal pathologies. Russell's Periodontal Index Score was used for the
evaluation of periodontal status of the subjects. RESULTS: While comparing the
mean CRP levels in all the three study groups, statistically significant results
were obtained. Statistically significant results were obtained while comparing
the mean CRP levels in group C patients before treatment and after treatment
therapy. The CRP levels were estimated by taking blood samples. Paired t-test and
one-way analysis of variance was used to assess the correlation between the two
parameters. CONCLUSION: Casual association might exist between the CRP levels and
periodontal diseases in pregnant women and the CRP levels may also get elevated
in pregnant women.
PMID- 27484603
TI - Nonsurgical Periodontal Therapy decreases the Severity of Rheumatoid Arthritis: A
Case-control Study.
AB - INTRODUCTION: Rheumatoid arthritis (RA) and periodontitis are common chronic
inflammatory conditions. Several studies suggested a relationship between RA and
periodontitis. Recent studies have shown a beneficial effect of periodontal
treatment on the severity of active RA. So the aim of this study was to examine
the effect of nonsurgical periodontal therapy on the clinical parameters of RA.
MATERIALS AND METHODS: A total of 60 subjects with moderate-to-severe chronic
generalized periodontitis and active RA in the age range 18 to 65 were selected
for the study. They were divided into two groups. Group A (control group)
consisted of 30 subjects with chronic generalized periodontitis and RA, and group
B of 30 subjects with chronic generalized peri-odontitis and RA and they received
nonsurgical periodontal therapy (scaling, root planning, and oral hygiene
instructions). Evaluation of clinical observations of Simplified Oral Hygiene
Index (OHI-S), gingival index (GI), bleeding on probing (BOP), probing pocket
depth (PPD), clinical attachment level (CAL), number of swollen joints (SJ),
number of tender joints (TJ), values of erythrocyte sedimentation rate (ESR),
visual analogue scale (VAS) for patient's global assessment, 3 months disease
activity score (DAS) index, and C-reactive protein (CRP) was done at baseline and
3 months. Statistical evaluation of clinical observations was carried out.
RESULTS: Group B subjects who received nonsurgical periodon-tal therapy showed
statistically significant improvement in all periodontal and RA parameters at 3
months, compared with group A who did not receive periodontal therapy.
CONCLUSION: It can be concluded from the result that nonsurgical periodontal
therapy may contribute to reduction in severity and symptoms of RA. CLINICAL
SIGNIFICANCE: Rheumatoid arthritis patients should be evaluated for periodontitis
and treated for the same in order to reduce its severity level.
PMID- 27484604
TI - Evaluation of Spontaneous Bone Regeneration after Enucleation of Large Cysts of
the Jaws using Radiographic Computed Software.
AB - INTRODUCTION: Spontaneous regeneration of bone is commonly seen in the small
surgical defects caused by enucleation of cysts. However, in case of large
surgical defects caused by the enucleation, spontaneous regeneration of bone is a
rare phenomenon and it depends on factors, such as age of the patient, intact
periosteum, and proper stabilization. MATERIALS AND METHODS: The study included
16 patients, who reported to the department of oral and maxillofacial surgery
with the complaint of pain and swelling in the jaws diagnosed as cyst. The sample
included equal numbers of male and female subjects aged between 15 and 40 years.
Panoramic radiographs were taken pre- and postoperatively on day 2 of the
enucleation. The dimensions of the cyst were evaluated on the radiograph
according to the proforma. Subsequent radiographs were taken at regular intervals
of 1.5, 3, and 6 months using standard parameters and were analyzed using MCIDTM
analysis software of imaging research. RESULTS: Mean reduction was seen in up to
39 and 60% in the cystic cavity size and increase in the mean density up to 59
and 90.2% at 3 and 6 months intervals respectively. CONCLUSION: Spontaneous bone
regeneration was seen even after primary closure of the large cystic defect
without the need for placement of foreign substances or grafts and it also
eliminated the complications resulting from placement of foreign substance.
Further studies are required in a larger sample with longer follow-up durations
to confirm the outcome of the present work for the benefit of patients. CLINICAL
SIGNIFICANCE: The present study depicted that spontaneous bone regeneration can
occur with accepted results after simple enucleation of jaw cyst without the aid
of any graft material. Hence, simple enucleation may be considered as a first
line of treatment modality for cystic lesion of the jaws. This simplifies the
surgical procedure, decreases the economic and biologic costs, and reduces the
risk of postoperative complications. Follow-up is necessary along with patient's
compliance for the success of treatment.
PMID- 27484605
TI - The Effect of Using Self-ligating Brackets on Maxillary Canine Retraction: A
Split-mouth Design Randomized Controlled Trial.
AB - INTRODUCTION: The results of previous studies about the efficacy of using self
ligating brackets (SLBs) in controlling canine movement during retraction are not
in harmony. Therefore, the current study aimed to compare the effects of using
new passive SLBs on maxillary canine retraction with sliding mechanics vs
conventional ligating brackets (CLBs) tied with metal ligatures. MATERIALS AND
METHODS: The sample comprised 15 adult patients (4 males, 11 females; 18-24
years) requiring bilateral extraction of maxillary first premolars. Units of
randomization are the left or right maxillary canines within the same patient.
The two maxillary canines in each patient were randomly assigned to one of the
two groups in a simple split-mouth design. The canines in the SLBs group (n = 15)
were bracketed with SLBs (Damon QTM), while the canines in the CLBs group (n =
15) were bracketed with conventional brackets (Mini Master Series). Transpalatal
bars were used for anchorage. After leveling and alignment, 0.019 * 0.025"
stainless steel working archwires were placed. Canines were retracted using a
nickel-titanium close-coil springs with a 150 gm force. The amount and rate of
maxillary canine retraction, canine rotation, and loss of anchorage were measured
on study models collected at the beginning of canine retraction (T0) and 12 weeks
later (T1). Differences were analyzed using paired-samples t-tests. RESULTS: The
effect differences were statistically significant (p < 0.001). Using Damon QTM
SLBs, the amount and rate of canine retraction were greater, while canine
rotation and anchorage loss were less. CONCLUSION: From a clinical perspective,
extraction space closure can be accomplished more effectively using SLBs.
CLINICAL SIGNIFICANCE: Self-ligating brackets gave better results compared to the
CLBs in terms of rate of movement, amount of canine rotation following
extraction, and anchorage loss.
PMID- 27484606
TI - Oral Cancer-related Inherited Cancer Syndromes: A Comprehensive Review.
AB - Oral squamous cell carcinoma is the most common malignancy of the oral cavity,
which is usually preceded by a myriad of oral potentially malignant disorders
(OPMDs). In the classification of OPMDs, inherited cancer syndromes (ICSs) were
proposed as one of the categories. Inherited cancer syndromes are genetic
disorders in which inherited genetic mutation in one or more genes predispose the
affected individuals to the development of cancer and may also cause its early
onset. Many of these syndromes are caused by mutations in tumor suppressor genes,
oncogenes, and genes involved in angiogenesis. General dental practitioners
frequently come across OPMDs in their day-to-day practice. It becomes of
paramount importance to have knowledge about these rare but prognostically
important OPMDs. With this view in mind, in this article, efforts have been made
to comprehensively discuss about various ICSs that have higher potential of
transformation into oral cancer. The ICSs discussed in this article are xeroderma
pigmentosum (XP), ataxia telangiectasia (AT), Bloom syndrome (BS), Fanconi's
anemia (FA), and Li-Fraumeni syndrome (LFS), with special emphasis on signs,
symptoms, and genetic considerations.
PMID- 27484607
TI - Decompensated HCV patients with co morbidities including HIV who are medically
treated are shown to minimize decompensation related admissions and healthcare
cost: A case series.
AB - Hepatitis C virus infection is a hot topic for both effective treatment and
elevated cost. This case series describes the cost saving for the healthcare
system of any nation of treating HCV in many situations, including that of overt
cirrhosis. Case#1 is of a HCV/HIV infected cirrhotic patient with MELD score of
17, Child Pugh score B, recurrent esophageal bleeds ceased after successful
treatment with sofosbuvir and simepravir. Case#2 is a patient also co-infected
with HCV/HIV MELD score of 18, Child Pugh score B, with grade 3 esophageal
varices and frequent bleed with significant anemia. With a regimen of sofosbuvir
and ribavirin the patient had no more hospitalization for GI bleed. HCV infection
is still underdiagnosed, picking up on it early, sufficient treatment and follow
up may reduce healthcare costs in the long run by significant measures.
PMID- 27484608
TI - Mapping the MMPI-2-RF Specific Problems Scales Onto Extant Psychopathology
Structures.
AB - A main objective in developing the Minnesota Multiphasic Personality Inventory-2
Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008 ) was to link the
hierarchical structure of the instrument's scales to contemporary psychopathology
and personality models for greater enhancement of construct validity. Initial
evidence published with the Restructured Clinical scales has indicated promising
results in that the higher order structure of these measures maps onto those
reported in the extant psychopathology literature. This study focused on
evaluating the internal structure of the Specific Problems and Interest scales,
which have not yet been examined in this manner. Two large, mixed-gender
outpatient and correctional samples were used. Exploratory factor analyses
revealed consistent evidence for a 4-factor structure representing somatization,
negative affect, externalizing, and social detachment. Convergent and
discriminant validity analyses in the outpatient sample yielded a pattern of
results consistent with expectations. These findings add further evidence to
indicate that the MMPI-2-RF hierarchy of scales map onto extant psychopathology
literature, and also add support to the notion that somatization and detachment
should be considered important higher order domains in the psychopathology
literature.
PMID- 27484609
TI - Improved Broth Microdilution Method for Antimicrobial Susceptibility Testing of
Francisella Noatunensis Orientalis.
AB - In this project we optimized a minimal inhibitory concentration testing protocol
for Francisella noatunensis orientalis. Thirty-three F. noatunensis orientalis
isolates recovered from different fish species and locations were tested, and
Escherichia coli ATCC 25922 was used as a quality control reference strain. A
modified cation-adjusted Mueller Hinton broth supplemented with 2% IsoVitalex and
0.1% glucose (MMH) was tested at a pH of 6.4 +/- 0.1, 7.1 +/- 0.1, and 7.3 +/-
0.1. Growth curves generated for F. noatunensis orientalis indicated that MMH at
a pH of 6.4 +/- 0.1 provided optimal growth. There were no significant
differences in the growth curves obtained from isolates recovered from different
fish species or from fresh or marine water. The pH of 6.4 +/- 0.1 in the MMH
media interfered with the inhibitory properties of the potentiated sulfonamides
(ormetoprim-sulfadimethoxine and trimethoprim-sulfamethoxazole) when using the E.
coli ATCC reference strain. Minimal inhibitory concentrations of eight
antimicrobials (gentamicin, enrofloxacin, ampicillin, oxytetracycline,
erythromycin, florfenicol, flumequine, and oxolinic acid) were similar for all F.
noatunensis orientalis isolates. The in vitro susceptibility data provided here
can provide a baseline for monitoring the development of antimicrobial resistance
among F. noatunensis orientalis isolates, as well as provide valuable data in the
development of potential therapeutics. Received October 27, 2015; accepted April
13, 2016.
PMID- 27484610
TI - Materials and surface modification for tissue engineered vascular scaffolds.
AB - Although vascular implantation has been used as an effective treatment for
cardiovascular disease for many years, off-the-shelf and regenerable vascular
scaffolds are still not available. Tissue engineers have tested various materials
and methods of surface modification in the attempt to develop a scaffold that is
more suitable for implantation. Extracellular matrix-based natural materials and
biodegradable polymers, which are the focus of this review, are considered to be
suitable materials for production of tissue-engineered vascular grafts. Various
methods of surface modification that have been developed will also be introduced,
their impacts will be summarized and assessed, and challenges for further
research will briefly be discussed.
PMID- 27484611
TI - LC-MS profiling of glucosinolates in the seeds of Brassica elongata Ehrh., and of
the two stenoendemic B. botteri Vis and B. cazzae Ginzb. & Teyber.
AB - The glucosinolates (GLs) present in seed extracts of Brassica elongata Ehrh., B.
botteri Vis and B. cazzae Ginzb. & Teyber from Croatia were identified by LC-MS.
4-Hydroxyindol-3-ylmethyl GL (3) was the major GL in the seeds of B. elongata,
along with the four minor GLs 2-(R)-hydroxy-3-butenyl- (1), 3-butenyl- (2), 4
pentenyl- (4) and indol-3-ylmethyl (5). The seeds of B. botteri (Vis island) and
B. cazzae (Susac island) contained 2 as the major GL as well as 1, 3, 5 and 4
methoxyindol-3-ylmethyl GL (6). However, the GLs in B. botteri (Palagruza island)
differed from other varieties having 2-propenyl GL (7) as the major GL in the
seeds, and the four minor GLs 2, 3, 5 and 6. This first report of the GL content
in the seeds of B. elongata, B. botteri and B. cazzae indicates that the unique
GL profiles could be specific to the geographical origin of the plant.
PMID- 27484612
TI - Red light activated "caged" reagents for microRNA research.
AB - "Caged" reagents for miRNA research (siRNA targeting EGFR, involved in miRNA
maturation, and mimics of miR-20a, playing a key role in tumor formation and
metastasis) were prepared. It was demonstrated that these reagents can be
activated by non-toxic to cells red light both in cells and in cell free
settings.
PMID- 27484613
TI - Spectroscopically Characterized Synthetic Mononuclear Nickel-Oxygen Species.
AB - Iron, copper, and manganese are the predominant metals found in oxygenases that
perform efficient and selective hydrocarbon oxidations and for this reason, a
large number of the corresponding metal-oxygen species has been described.
However, in recent years nickel has been found in the active site of enzymes
involved in oxidation processes, in which nickel-dioxygen species are proposed to
play a key role. Owing to this biological relevance and to the existence of
different catalytic protocols that involve the use of nickel catalysts in
oxidation reactions, there is a growing interest in the detection and
characterization of nickel-oxygen species relevant to these processes. In this
Minireview the spectroscopically/structurally characterized synthetic superoxo,
peroxo, and oxonickel species that have been reported to date are described. From
these studies it becomes clear that nickel is a very promising metal in the field
of oxidation chemistry with still unexplored possibilities.
PMID- 27484614
TI - Atypical Cat Scratch Disease With Hepatosplenic Involvement.
PMID- 27484615
TI - Xanthogranulomatous Cholecystitis as the Cause of Abdominal Pain in a 15-Year-Old
Boy.
PMID- 27484617
TI - Direct NHC-catalysed redox amidation using CO2 for traceless masking of amine
nucleophiles.
AB - The N-heterocyclic carbene (NHC)-catalysed redox amidation reaction is poorly
developed and usually requires catalytic co-additives for electron-rich amine
nucleophiles. We report a masking strategy (using CO2) that couples release of
the free amine nucleophile to catalytic turnover, and in doing so, enables direct
catalytic redox amidation of electron-rich amines.
PMID- 27484616
TI - A Multinuclear Metal Complex Based DNase-Mimetic Artificial Enzyme: Matrix
Cleavage for Combating Bacterial Biofilms.
AB - Extracellular DNA (eDNA) is an essential structural component during biofilm
formation, including initial bacterial adhesion, subsequent development, and
final maturation. Herein, the construction of a DNase-mimetic artificial enzyme
(DMAE) for anti-biofilm applications is described. By confining passivated gold
nanoparticles with multiple cerium(IV) complexes on the surface of colloidal
magnetic Fe3 O4 /SiO2 core/shell particles, a robust and recoverable artificial
enzyme with DNase-like activity was obtained, which exhibited high cleavage
ability towards both model substrates and eDNA. Compared to the high
environmental sensitivity of natural DNase in anti-biofilm applications, DMAE
exhibited a much better operational stability and easier recoverability. When
DMAE was coated on substratum surfaces, biofilm formation was inhibited for
prolonged periods of time, and the DMAE excelled in the dispersion of established
biofilms of various ages. Finally, the presence of DMAE remarkably potentiated
the efficiency of traditional antibiotics to kill biofilm-encased bacteria and
eradiate biofilms.
PMID- 27484618
TI - Laserballoon and Cryoballoon Pulmonary Vein Isolation in Persistent and
Longstanding Persistent Atrial Fibrillation.
AB - BACKGROUND: Visually guided laserballoon (LB) ablation has recently been
introduced for pulmonary vein (PV) isolation (PVI). We analyzed efficacy and
safety results of the newly introduced LB ablation technique in patients with
persistent and longstanding persistent atrial fibrillation (AF), and compared
this with an established standard method using the cryoballoon (CB). METHODS: A
total of 35 patients with symptomatic persistent AF underwent LB ablation and
were followed-up for 1 year. Results were compared to 35 patients who underwent
CB ablation at the same institution and case matched for age, sex, CHA2 DS2 -VASc
score, and left atrial volume. RESULTS: Complete isolation of all PVs was
achieved in 68.6% in the LB and 97.1% in the CB group (P < 0.01). No significant
differences were found for AF-free survival after 12 months in the complete
cohort of all patients (LB: 53.3% vs CB: 70.4%; P = n.s.) and after excluding
patients without complete PVI (LB: 57.8% vs CB: 72.5%; P = n.s.). LB ablation
resulted in longer procedure (158.5 +/- 37.9 minutes vs 110.9 +/- 26.5 minutes; P
< 0.01) and fluoroscopy durations (28.4 +/- 11.1 minutes vs 23.5 +/- 9.4 minutes;
P = 0.04.), and a trend toward more major complications (14.3% vs 2.9%; P =
n.s.). Procedure durations and complications declined over time and were level
with CB-treated patients when reaching the last quartile of the LB patients.
CONCLUSION: PVI in patients with persistent AF using the LB or the CB resulted in
comparable success rates. Initial prolongations in procedure and safety
parameters as a result of a learning curve effect for the LB have to be
considered before starting to use this technique.
PMID- 27484619
TI - Macromolecular crowding explains overflow metabolism in cells.
AB - Overflow metabolism is a metabolic phenotype of cells characterized by mixed
oxidative phosphorylation (OxPhos) and fermentative glycolysis in the presence of
oxygen. Recently, it was proposed that a combination of a protein allocation
constraint and a higher proteome fraction cost of energy generation by OxPhos
relative to fermentation form the basis of overflow metabolism in the bacterium,
Escherichia coli. However, we argue that the existence of a maximum or optimal
macromolecular density is another essential requirement. Here we re-evaluate our
previous theory of overflow metabolism based on molecular crowding following the
proteomic fractions formulation. We show that molecular crowding is a key factor
in explaining the switch from OxPhos to overflow metabolism.
PMID- 27484620
TI - Ovarian nongestational choriocarcinoma and associated adenocarcinoma with the
same germ cell origin determined by a molecular genetic approach: A case report.
AB - Ovarian non-gestational choriocarcinomas co-existing with adenocarcinoma are
extremely rare and have been reported as epithelial ovarian carcinomas of a "non
germ cell origin" with "choriocarcinomatous differentiation". Although the
cellular origin of non-gestational choriocarcinoma may be post-meiotic ovarian
germ cells or the dedifferentiation of epithelial ovarian carcinoma, detailed
genetic evidence has not yet been obtained to support this. We herein present a
case of ovarian non-gestational choriocarcinoma co-existing with adenocarcinoma
in a 29-year-old woman. The tumor rapidly increased in size and lung metastases
appeared soon after parturition. We genetically demonstrated that the cellular
origin of ovarian non-gestational choriocarcinoma was a post-meiotic germ cell
derivation using a short tandem repeat analysis. The co-existing adenocarcinoma
component was also shown to be of the same germ cell origin. These tumors showed
the same homozygous pattern. A molecular genetic approach may be important for
understanding the clinicopathological features of such tumors.
PMID- 27484621
TI - Automated detection and labeling of high-density EEG electrodes from structural
MR images.
AB - OBJECTIVE: Accurate knowledge about the positions of electrodes in
electroencephalography (EEG) is very important for precise source localizations.
Direct detection of electrodes from magnetic resonance (MR) images is
particularly interesting, as it is possible to avoid errors of co-registration
between electrode and head coordinate systems. In this study, we propose an
automated MR-based method for electrode detection and labeling, particularly
tailored to high-density montages. APPROACH: Anatomical MR images were processed
to create an electrode-enhanced image in individual space. Image processing
included intensity non-uniformity correction, background noise and goggles
artifact removal. Next, we defined a search volume around the head where
electrode positions were detected. Electrodes were identified as local maxima in
the search volume and registered to the Montreal Neurological Institute standard
space using an affine transformation. This allowed the matching of the detected
points with the specific EEG montage template, as well as their labeling.
Matching and labeling were performed by the coherent point drift method. Our
method was assessed on 8 MR images collected in subjects wearing a 256-channel
EEG net, using the displacement with respect to manually selected electrodes as
performance metric. MAIN RESULTS: Average displacement achieved by our method was
significantly lower compared to alternative techniques, such as the
photogrammetry technique. The maximum displacement was for more than 99% of the
electrodes lower than 1 cm, which is typically considered an acceptable upper
limit for errors in electrode positioning. Our method showed robustness and
reliability, even in suboptimal conditions, such as in the case of net rotation,
imprecisely gathered wires, electrode detachment from the head, and MR image
ghosting. SIGNIFICANCE: We showed that our method provides objective, repeatable
and precise estimates of EEG electrode coordinates. We hope our work will
contribute to a more widespread use of high-density EEG as a brain-imaging tool.
PMID- 27484623
TI - A CRISPR-Cas9 sex-ratio distortion system for genetic control.
AB - Genetic control aims to reduce the ability of insect pest populations to cause
harm via the release of modified insects. One strategy is to bias the
reproductive sex ratio towards males so that a population decreases in size or is
eliminated altogether due to a lack of females. We have shown previously that sex
ratio distortion can be generated synthetically in the main human malaria vector
Anopheles gambiae, by selectively destroying the X-chromosome during
spermatogenesis, through the activity of a naturally-occurring endonuclease that
targets a repetitive rDNA sequence highly-conserved in a wide range of organisms.
Here we describe a CRISPR-Cas9 sex distortion system that targets ribosomal
sequences restricted to the member species of the Anopheles gambiae complex.
Expression of Cas9 during spermatogenesis resulted in RNA-guided shredding of the
X-chromosome during male meiosis and produced extreme male bias among progeny in
the absence of any significant reduction in fertility. The flexibility of CRISPR
Cas9 combined with the availability of genomic data for a range of insects
renders this strategy broadly applicable for the species-specific control of any
pest or vector species with an XY sex-determination system by targeting sequences
exclusive to the female sex chromosome.
PMID- 27484622
TI - Mental disorders among college students in the World Health Organization World
Mental Health Surveys.
AB - BACKGROUND: Although mental disorders are significant predictors of educational
attainment throughout the entire educational career, most research on mental
disorders among students has focused on the primary and secondary school years.
METHOD: The World Health Organization World Mental Health Surveys were used to
examine the associations of mental disorders with college entry and attrition by
comparing college students (n = 1572) and non-students in the same age range (18
22 years; n = 4178), including non-students who recently left college without
graduating (n = 702) based on surveys in 21 countries (four low/lower-middle
income, five upper-middle-income, one lower-middle or upper-middle at the times
of two different surveys, and 11 high income). Lifetime and 12-month prevalence
and age-of-onset of DSM-IV anxiety, mood, behavioral and substance disorders were
assessed with the Composite International Diagnostic Interview (CIDI). RESULTS:
One-fifth (20.3%) of college students had 12-month DSM-IV/CIDI disorders; 83.1%
of these cases had pre-matriculation onsets. Disorders with pre-matriculation
onsets were more important than those with post-matriculation onsets in
predicting subsequent college attrition, with substance disorders and, among
women, major depression the most important such disorders. Only 16.4% of students
with 12-month disorders received any 12-month healthcare treatment for their
mental disorders. CONCLUSIONS: Mental disorders are common among college
students, have onsets that mostly occur prior to college entry, in the case of
pre-matriculation disorders are associated with college attrition, and are
typically untreated. Detection and effective treatment of these disorders early
in the college career might reduce attrition and improve educational and
psychosocial functioning.
PMID- 27484624
TI - Synthetic and Natural Lipase Inhibitors.
AB - Lipases are enzymes that catalyse the hydrolysis of ester bonds of triglycerides
ranging among biocatalysts of considerable physiological significance and
industrial potential. Better understanding of the catalytic functions and
achieving the possibility to control the biocatalysis process, in particular
exploring some activators and inhibitors of lipases, seems to be crucial in the
context of novel applications. The lipase activity is a function of interfacial
composition: the enzyme can be there activated as well as denaturated or
deactivated and the interface is an appropriate site for modulating lipolysis.
Lipase inhibitor, interacts directly with the enzyme and inhibits lipase action.
Alternatively, some compounds can postpone the lipolytic reaction via adsorption
to the interphase or to the substrate molecules. The aim of this review is to
summarise the current knowledge concerning human, animal and microbial lipase
inhibitors, which were grouped into two categories: synthetic lipase inhibitors
(including phosphonates, boronic acids and fats analogues) and natural compounds
(including beta-lactones and some botanical foodstuffs - plant extracts and plant
metabolites, mainly polyphenols and saponins as well as peptides and some dietary
fibers). The topics discussed include also inhibition issues from the viewpoint
of obesity treatment. Among natural compounds able to inhibit lipase activity are
beta- lactones including orlistat. Orlistat is the only registered drug for
obesity treatment in many countries and lipases are essential enzymes for lipid
absorption - thus fat absorption or obesity can be controlled by lipase
inhibition, especially pancreatic lipase which is responsible for the hydrolysis
of over 80% of total dietary fats. Its effectiveness in obesity treatment was
also described.
PMID- 27484625
TI - New Progress in Azole Compounds as Antimicrobial Agents.
AB - The increasing incidence of microbial resistance and newly emerging pathogens
have become a serious challenge for public health. More and more efforts have
been directed to the development of new antimicrobial agents with distinct
mechanisms from the well-known classes of clinical drugs. The extensive clinical
utilization of azole-based medicinal drugs has evoked numerous attentions, and
their researches and developments have been a quite rapid developing and active
highlight topic with an infinite space. Consideration of our researches on azole
compounds and other literature in recent three years, this review scientifically
reviewed the new progress of azole derivatives as antibacterial, antifungal,
antitubercular and antiviral agents, including mono-nitrogen azoles (oxazoles,
thiazoles and carbazoles), bis-nitrogen azoles (imidazoles, pyrazoles and
benzimidazoles) and tri-nitrogen azoles (triazoles and benzotriazoles) as well as
tetrazole derivatives. It was hoped that this review would be helpful for the
design and development of highly efficient azole derivatives with high
bioactivity and low toxicity.
PMID- 27484626
TI - Evolving Novel Chemical Entities for Management of Benign Prostatic Hyperplasia.
AB - BACKGROUND: Proliferation of the smooth muscle and epithelial cells within the
prostatic transition zone in older men leads to benign prostatic hyperplasia
(BPH), which is hallmarked by the troublesome lower urinary tract symptoms. The
affair responsible for the initiation and promotion of disease is still
unresolved, though alpha-blockers and 5alpha-reductase inhibitors are used as
management options for relief from the dynamic and static components
respectively. METHOD: Combination therapy including both the alpha blocker and
5alpha-reductase inhibitor is emerging as inclusive parcel for treatment.
However, selective androgen receptor modulators (SARM) and selective estrogen
receptor modulators (SERM) are the other management resources, which are in the
limelight. RESULT: This review gives a glimpse of BPH and the various chemical
entities which have been reported in literature till date for the condition since
2005.
PMID- 27484628
TI - Synergistic photomagnetic effects in coordination polymer heterostructure
particles of Hofmann-like Fe(4-phenylpyridine)2[Ni(CN)4].0.5H2O and
K0.4Ni[Cr(CN)6]0.8.nH2O.
AB - New nanometer scale heterostructure particles of the two-dimensional Hofmann-like
Fe(ii) spin-crossover network, Fe(phpy)2[Ni(CN)4].0.5H2O {phpy = 4
phenylpyridine}, and the Prussian blue analogue K0.4Ni1.0[Cr(CN)6]0.8.nH2O (NiCr
PBA) have been developed, exhibiting synergistic photomagnetic effects, whereby
the LIESST (light-induced electron spin-state trapping) effect in the Hofmann
like material induces a magnetization change in the NiCr-PBA. A variety of
microscopic and spectroscopic techniques demonstrate the heterogeneous growth of
the NiCr-PBA on the Hofmann seed particles and show the Hofmann compound retains
its thermal and photoinduced spin transition properties in the heterostructure.
The photoinduced magnetization change in the NiCr-PBA network arises from
coupling of the two lattices despite dissimilar structure types. Isothermal
magnetization minor hysteresis loop studies at 5 K show light absorption leads to
changes in the local anisotropy of NiCr-PBA magnetic domains, providing direct
evidence for a general magnetomechanical mechanism of light-switchable magnetism
in coordination polymer heterostructures combining a photoactive material with a
magnet.
PMID- 27484627
TI - Recent Advances in the Discovery of HIF-1alpha-p300/CBP Inhibitors as Anti-Cancer
Agents.
AB - Hypoxia-inducible factor-1 (HIF-1), a heterodimeric (containing alpha and beta
subunits) transcription factor, is involved in hypoxia response pathway that
regulates the expression of many tumorrelated genes. The stabilized HIF-1
heterodimer couples to the general co-activators p300/CBP (CREB binding protein),
forming an active transcription factor to initiate hypoxic responses. Inhibiting
the transcription factor-coactivator HIF-1alpha-p300/CBP interaction represents
an attractive approach for blocking hypoxia pathway in tumors. Recently, diverse
HIF-1alpha-p300/CBP inhibitors have been designed and their anti-tumor activities
have been evaluated. The developments of inhibitors of HIF-1alpha- p300/CBP are
discussed in this review. An outline of structures and biological activities of
these inhibitors can be traced, along with the approaches for inhibitors
discovery. The challenges in identifying novel and selective potent inhibitors of
HIF-1alpha-p300/CBP are also put forward.
PMID- 27484629
TI - Modulatory effects of levamisole and garlic oil on the immune response of Wistar
rats: Biochemical, immunohistochemical, molecular and immunological study.
AB - Levamisole (LEVA) and garlic are prevalent immunomodulators in humans and
animals. Therefore, the present study aimed to examine the immunomodulatory
effects of LEVA and garlic oil (GO) alone or in combination on the immune
response of Wistar rats. A total of 24 male Wistar rats were allocated into four
equal groups: Control group, which was given ad libitum access to food and water;
and groups 2-4, which were orally administered LEVA [2.5 mg/kg body weight (BW)
every 2 days], GO, (5 ml/kg BW daily), or LEVA plus GO, respectively for 4
consecutive weeks. Serum immunoglobulin (Ig)G and IgM levels were measured using
a radial immunodiffusion assay. Serum cytokine levels, including interferon (IFN)
gamma, interleukin (IL)-5 and tumor necrosis factor (TNF)-alpha, were measured
using enzyme-linked immunosorbent assay kits. Total blood counts were measured
automatically using a cell counter. Serum lysozyme enzymatic activity was
determined by measuring the diameters of the zones of clearance relative to
lysozyme. Immunohistochemical detection of CD4 and CD8 was carried out using the
streptavidin-biotin-peroxidase method. Furthermore, the mRNA expression levels of
IL-4, IL-5 and IL-12 were measured in the leukocytes and thymus gland by semi
quantitative polymerase chain reaction. The results revealed that LEVA increased
serum levels of IFN-gamma, IL-5 and TNF-alpha cytokines, whereas co
administration of LEVA and GO decreased the stimulatory action of LEVA alone.
LEVA and GO alone increased the serum levels of IgG, IgM and total blood cell
counts, and co-administration of GO and LEVA inhibited the effects of LEVA. At
the cellular level, in the spleen, LEVA increased immunoreactivity of CD4 and
CD8, whereas co-administration of GO with LEVA decreased this strong expression.
At the molecular level, in leukocytes, LEVA upregulated the mRNA expression
levels of IL-2, IL-4 and IL-5, whereas GO alone downregulated mRNA expression. Co
administration of GO with LEVA inhibited the LEVA-induced upregulation of IL-2,
IL-4 and IL-5 mRNA expression. In the thymus, both LEVA and GO upregulated the
mRNA expression levels of IL-4 and IL-5, whereas LEVA alone did not affect IL-12
mRNA expression. Co-administration of GO with LEVA inhibited LEVA-induced
upregulation of IL-4 and GO-induced upregulation of IL-12 expression, and had an
additive upregulatory effect on IL-5 expression. In conclusion, LEVA stimulated T
helper (Th)1 cytokines, whereas GO stimulated a Th2 response, and co
administration of GO with LEVA inhibited the stimulatory effects of LEVA and
balanced the Th1/Th2 response.
PMID- 27484631
TI - Cognitive performance, fatigue and event-related potentials in patients with
clinically isolated syndrome.
AB - OBJECTIVES: Cognitive impairment and fatigue are regarded as important aspects of
multiple sclerosis. The aim of this study was to evaluate cognitive performance,
the level of fatigue and parameters of event-related potentials (ERP) in patients
diagnosed with clinically isolated syndrome (CIS). PATIENTS AND METHODS: The
study comprised 44 patients with CIS and 45 healthy controls. Cognitive
performance was assessed using the Brief Repeatable Battery of Neuropsychological
Tests (BRBNT), fatigue - using the Fatigue Severity Scale (FSS) and Modified
Fatigue Impact Scale (MFIS). Auditory ERP were performed and the parameters of
N200 and P300 components were analyzed. Neuropsychological and
electrophysiological measures were referred to clinical and radiological features
of the disease activity. RESULTS: Forty five% of patients failed in at least one
test from BRBNT, mainly within the domains of memory and attention. In 18% of
patients FSS corresponded with moderate or severe fatigue. The mean latency of
N200 and P300 was significantly longer and amplitude of P300 was lower in those
patients with CIS than in the controls. Significant correlations were found
between the results of MFIS and tests evaluating verbal memory and attention, as
well as between N200 latency and results of tests for verbal memory. CONCLUSIONS:
Cognitive performance and fatigue deserve attention from the earliest clinical
stage of MS. Abnormalities of event-related potentials in CIS suggest early
impact of the disease on functional neural networks.
PMID- 27484630
TI - The dimerization equilibrium of a ClC Cl(-)/H(+) antiporter in lipid bilayers.
AB - Interactions between membrane protein interfaces in lipid bilayers play an
important role in membrane protein folding but quantification of the strength of
these interactions has been challenging. Studying dimerization of ClC-type
transporters offers a new approach to the problem, as individual subunits adopt a
stable and functionally verifiable fold that constrains the system to two states
monomer or dimer. Here, we use single-molecule photobleaching analysis to
measure the probability of ClC-ec1 subunit capture into liposomes during
extrusion of large, multilamellar membranes. The capture statistics describe a
monomer to dimer transition that is dependent on the subunit/lipid mole fraction
density and follows an equilibrium dimerization isotherm. This allows for the
measurement of the free energy of ClC-ec1 dimerization in lipid bilayers,
revealing that it is one of the strongest membrane protein complexes measured so
far, and introduces it as new type of dimerization model to investigate the
physical forces that drive membrane protein association in membranes.
PMID- 27484632
TI - Improving the applicability of guidelines on nonmelanoma skin cancer in frail
older adults: a multidisciplinary expert consensus and systematic review of
current guidelines.
AB - BACKGROUND: Balancing treatment decisions in frail older adults with nonmelanoma
skin cancer (NMSC) can be challenging. Clinical practice guidelines (CPGs) could
provide assistance. OBJECTIVES: To collect and prioritize items related to frail
older adults with NMSC for integration into CPGs and to assess the current extent
of this integration. METHODS: Items were collected and prioritized by a
multidisciplinary working group (29 members) using a modified Delphi procedure
and a five-point Likert scale. To assess current integration of these items in
CPGs, a systematic review was subsequently performed by two independent reviewers
using five medical databases (PubMed, Embase, Cochrane Library, SUMsearch and
Trip Database), websites of guideline developers/databases, and (inter)national
dermatological societies. RESULTS: Prioritization of a final 13-item list showed
that 'limited life expectancy' (4.5 +/- 0.9) and 'treatment goals other than
cure' (4.4 +/- 0.7) were most desired to be integrated into CPGs; both were
included in six (46%) of the CPGs found (n = 13). Attention to 'tumour
characteristics' and 'comorbidities' were included in CPGs most often (100% and
77%, respectively). CONCLUSIONS: More attention to items related to frail older
adults in NMSC CPGs is broadly desired, but CPG integration of these items is
currently limited. More integration might stimulate more holistic, personalized
and patient-centred care in frail older adults.
PMID- 27484633
TI - Dimers or trimers? A characterization of the halogen bonded complexes of CF3X
(X=I or Br) with dimethyl ether and acetone in cryosolutions.
AB - Acetone molecules dissolved in liquid krypton are inclined to self-associate into
dimers. This behavior affects its use as a prototype Lewis base in studies of
weak intermolecular interactions. In this study infrared spectra of mixed
solutions of dimethyl ether and CF3X and of acetone and CF3X (with X=I or Br)
dissolved in liquid argon and liquid krypton are recorded at constant
temperature. The dataset for dimethyl ether is used to validate a numerical
method based on least-squares fitting of a model including contributions of both
monomers and a heterodimer with 1:1 stoichiometry. The resulting monomer and
dimer spectra show excellent agreement with previous studies found in literature.
The analysis of the dataset for acetone requires an extension of the model with
contributions for the acetone homodimer and for (acetone)2.CF3X and
acetone.(CF3X)2 trimers. The results show that many signals for acetone.CF3I and
(acetone)2.CF3I are observed, while only a few bands due to acetone.(CF3I)2
occur. The use of numerical approaches adjusted to the specificities of a mixture
of two compounds allows to reliably resolve overlapping spectra of monomers and
heterocomplexes and characterizing heterocomplex features that could not be
deduced using earlier methods. To support the assignments made, ab initio
calculations predicting geometries, relative stabilities and harmonic vibrational
frequencies for the species envisaged are performed.
PMID- 27484634
TI - Resting state theta band source distribution and functional connectivity in
remitted schizophrenia.
AB - Increased resting theta activity is one consistent observation occurring during
all the phases of schizophrenia. However, the resting theta oscillations during
the remission phase are yet unclear. We studied resting theta current source
density and functional connectivity in remitted schizophrenia and compared with
healthy controls. Significantly increased current source density was found in the
dominant anterior cingulate cortex. Increased connectivity between the inferior
parietal lobe bilaterally and between the left inferior parietal lobe and right
middle frontal gyrus was also found. It may be concluded that schizophrenia
patients have aberrant regional theta band current source density and functional
connectivity even during remission.
PMID- 27484635
TI - Decreased VEGFR2 expression and increased phosphorylated Akt1 in the prefrontal
cortex of individuals with schizophrenia.
AB - The Akt signaling pathway involves various cellular processes and depends on
extracellular stimuli. Since Akt signaling participates in cytoprotection,
synapse plasticity, axon extension, and neurotransmission in the nervous system,
alteration in Akt signaling might be a potential cause of schizophrenia. In this
study, we performed multiplex fluorescent bead based immunoassays for members of
the Akt signaling pathway in postmortem brains of controls and patients with
schizophrenia. Vascular endothelial growth factor receptor 2 (VEGFR2/KDR) was
significantly decreased in the prefrontal cortex (PFC) of patients with
schizophrenia, and the expression level of VEGFR2 was inversely correlated with
the positive symptom subscale of the Diagnostic Instrument for Brain Studies
(DIBS) in patients with schizophrenia. There was also an increase in
phosphorylated Akt1 in the PFC in the patients, though the ratio of phospho/total
Akt1 is not significantly different. In the nucleus accumbens (NAcc) there was no
significant difference in expression and phosphorylation levels of Akt signaling
proteins. Genetic analysis revealed a significant correlation of a SNP of KDR
(rs7692791) with ERK1/2 and Akt1 phospho/total rates. Since VEGFR2 participates
in angiogenesis and neurotrophic activation, either or both functions might be
responsible for onset of schizophrenia.
PMID- 27484636
TI - Tannerella forsythia GroEL induces inflammatory bone resorption and synergizes
with interleukin-17.
AB - Tannerella forsythia is a major periodontal pathogen, and T. forsythia GroEL is a
molecular chaperone homologous to human heat-shock protein 60. Interleukin-17 (IL
17) has been implicated in the pathogenesis of periodontitis and several systemic
diseases. This study investigated the potential of T. forsythia GroEL to induce
inflammatory bone resorption and examined the cooperative effect of IL-17 and T.
forsythia GroEL on inflammatory responses. Human gingival fibroblasts (HGFs) and
periodontal ligament (PDL) fibroblasts were stimulated with T. forsythia GroEL
and/or IL-17. Gene expression of IL-6, IL-8, and cyclooxygenase-2 (COX-2) and
concentrations of IL-6, IL-8, and prostaglandin E2 (PGE2 ) were measured by real
time reverse transcription polymerase chain reaction and enzyme-linked
immunosorbent assays, respectively. After stimulation of MG63 cells with T.
forsythia GroEL and/or IL-17, gene expression of osteoprotegerin (OPG) was
examined. After subcutaneous injection of T. forsythia GroEL and/or IL-17 above
the calvaria of BALB/c mice, calvarial bone resorption was assessed by micro
computed tomography and histological examination. Tannerella forsythia GroEL
induced IL-6 and IL-8 production in HGFs and PDL cells, and IL-17 further
promoted IL-6 and IL-8 production. Both T. forsythia GroEL and IL-17
synergistically increased PGE2 production and inhibited OPG gene expression.
Calvarial bone resorption was induced by T. forsythia GroEL injection, and
simultaneous injection of T. forsythia GroEL and IL-17 further increased bone
resorption. These results suggest that T. forsythia GroEL is a novel virulence
factor that can contribute to inflammatory bone resorption caused by T. forsythia
and synergizes with IL-17 to exacerbate inflammation and bone resorption.
PMID- 27484637
TI - Melatonin-induced increase in sensitivity of human hepatocellular carcinoma cells
to sorafenib is associated with reactive oxygen species production and mitophagy.
AB - Effects of sorafenib in hepatocellular carcinoma (HCC) are frequently transient
due to tumor-acquired resistance, a phenotype that could be targeted by other
molecules to reduce this adaptive response. Because melatonin is known to exert
antitumor effects in HCC cells, this study investigated whether and how melatonin
reduces resistance to sorafenib. Susceptibility to sorafenib (10 nmol/L to 50
MUmol/L) in the presence of melatonin (1 and 2 mmol/L) was assessed in HCC cell
lines HepG2, HuH7, and Hep3B. Cell viability was reduced by sorafenib from 1
MUmol/L in HepG2 or HuH7 cells, and 2.5 MUmol/L in Hep3B cells. Co-administration
of melatonin and sorafenib exhibited a synergistic cytotoxic effect on HepG2 and
HuH7 cells, while Hep3B cells displayed susceptibility to doses of sorafenib that
had no effect when administrated alone. Co-administration of 2.5 MUmol/L
sorafenib and 1 mmol/L melatonin induced apoptosis in Hep3B cells, increasing
PARP hydrolysis and BAX expression. We also observed an early colocalization of
mitochondria with lysosomes, correlating with the expression of mitophagy markers
PINK1 and Parkin and a reduction of mitofusin-2 and mtDNA compared with sorafenib
administration alone. Moreover, increased reactive oxygen species production and
mitochondrial membrane depolarization were elicited by drug combination,
suggesting their contribution to mitophagy induction. Interestingly, Parkin
silencing by siRNA to impair mitophagy significantly reduced cell killing, PARP
cleavage, and BAX expression. These results demonstrate that the pro-oxidant
capacity of melatonin and its impact on mitochondria stability and turnover via
mitophagy increase sensitivity to the cytotoxic effect of sorafenib.
PMID- 27484638
TI - Canine distemper virus isolated from a monkey efficiently replicates on Vero
cells expressing non-human primate SLAM receptors but not human SLAM receptor.
AB - BACKGROUND: In 2008, an outbreak of canine distemper virus (CDV) infection in
monkeys was reported in China. We isolated CDV strain (subsequently named Monkey
BJ01-DV) from lung tissue obtained from a rhesus monkey that died in this
outbreak. We evaluated the ability of this virus on Vero cells expressing SLAM
receptors from dog, monkey and human origin, and analyzed the H gene of Monkey
BJ01-DV with other strains. RESULTS: The Monkey-BJ01-DV isolate replicated to the
highest titer on Vero cells expressing dog-origin SLAM (10(5.2+/-0.2) TCID50/ml)
and monkey-origin SLAM (10(5.4+/-0.1) TCID50/ml), but achieved markedly lower
titers on human-origin SLAM cells (10(3.3+/-0.3) TCID50/ml). Phylogenetic
analysis of the full-length H gene showed that Monkey-BJ01-DV was highly related
to other CDV strains obtained during recent CDV epidemics among species of the
Canidae family in China, and these Monkey strains CDV (Monkey-BJ01-DV, CYN07-dV,
Monkey-KM-01) possessed a number of amino acid specific substitutions (E276V,
Q392R, D435Y and I542F) compared to the H protein of CDV epidemic in other
animals at the same period. CONCLUSIONS: Our results suggested that the monkey
origin-CDV-H protein could possess specific substitutions to adapt to the new
host. Monkey-BJ01-DV can efficiently use monkey- and dog-origin SLAM to infect
and replicate in host cells, but further adaptation may be required for efficient
replication in host cells expressing the human SLAM receptor.
PMID- 27484640
TI - New congenital coronary artery anomaly - double supply of single left anterior
descending coronary artery from the left and right coronary sinuses: a case
report.
AB - BACKGROUND: A normal anatomy of coronary arteries is important to have adequate
cardiac muscle blood supply especially during extraneous physical activities.
This case report describes a rare coronary anomaly in which the accessory
coronary artery arose from the right coronary artery, reentered the left anterior
descending coronary artery, and then ran as a single vessel. CASE PRESENTATION:
We present a case of a coronary anomaly in a 47-year-old white man who presented
with atypical angina. Computed tomographic angiography and coronary angiography
showed a variant of dual left anterior descending coronary artery not previously
described. Our patient's accessory coronary artery arose from his right coronary
artery. It took an intramuscular course beneath the right ventricular outflow
tract in the interventricular septal area to the anterior interventricular
sulcus, giving off septal perforators that reentered his medial left anterior
descending coronary artery. Both vessels ran after the anastomosis in the
anterior interventricular sulcus as a single vessel. CONCLUSIONS: We propose that
this anomaly represents a new variant of coronary artery anomaly. This coronary
artery anomaly does not cause ischemia. Recognition of this coronary anomaly is
important in patients undergoing percutaneous coronary intervention or coronary
artery bypass graft operations.
PMID- 27484639
TI - Overexpression of the miR-141/200c cluster promotes the migratory and invasive
ability of triple-negative breast cancer cells through the activation of the FAK
and PI3K/AKT signaling pathways by secreting VEGF-A.
AB - BACKGROUND: The role of microRNA-200 (miR-200) family members in the migration
and invasion of breast cancer is controversial. This study investigated the
mechanisms by which the miR-200 family members modulated the migratory and
invasive abilities of an aggressive triple-negative breast cancer (TNBC) cell
line, MDA-MB-231. METHODS: The miR-200 family (miR-200b/200a/429 and miR-141/200c
clusters) and green fluorescence protein (GFP) were transduced into MDA-MB-231
cells using a lentiviral system. Stable cells highly expressing the miR-200
family and GFP were isolated by puromycin selection and fluorescence-activated
cell sorting. Gene expression was evaluated using real-time polymerase chain
reaction (PCR) and reverse transcriptase-PCR (RT-PCR). The migratory and invasive
abilities were assessed using trans-well and wound-healing assays. The secreted
cytokines and growth factors in cultured media were quantified using a Bio
Plex200 multiplex array system. Western blot assays and immunofluorescence
staining were conducted to investigate miR-200 family-regulated signaling
pathways. The entire dataset obtained in this study was statistically evaluated
using a one-way ANOVA followed by a t-test. RESULTS: The stable overexpression of
the miR-200b/200a/429 or miR-141/200c cluster suppressed cell growth and
significantly increased migration and invasion of MDA-MB-231 cells. miR-141/200c
overexpression was more effective in decreasing cell growth and promoting
migration and invasion of MDA-MB-231 cells than was miR-200b/200a/429
overexpression. In addition, the overexpression of the miR-200b/200a/429 or miR
141/200c cluster led to an increase in the phosphorylation of focal adhesion
kinase (FAK) and protein kinase B (AKT). Chemical inhibitors of FAK and
phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT suppressed the
migration and invasion of MDA-MB-231 cells that was enhanced by the
overexpression of the miR-200b/200a/429 or miR-141/200c cluster. Compared to the
miR-200b/200a/429 cluster-transduced MDA-MB-231 cells, the miR-141/200c cluster
transduced MDA-MB-231 cells exhibited a significant increase in vascular
endothelial growth factor (VEGF)-A secretion and integrin-alphaV (integrin
alphaV) expression. Treatment with an anti-VEGF-A-neutralizing antibody inhibited
the increase in migration and invasion in both the miR-200b/200a/429- and miR
141/200c-transduced MDA-MB-231 cells but significantly reduced the
phosphorylation of FAK and AKT in only the miR-141/200c cluster-transduced MDA-MB
231 cells. CONCLUSIONS: Taken together, our data demonstrate a mechanism in which
the miR-141/200c cluster, through FAK- and PI3K/AKT-mediated signaling by means
of increased VEGF-A secretion, promotes the migratory and invasive abilities of
MDA-MB-231 cells.
PMID- 27484641
TI - Protein kinase A inhibitor, H89, significantly enhances survival rate of
dissociated human embryonic stem cells following cryopreservation.
AB - OBJECTIVES: Human embryonic stem cells (hESCs) have huge potential for
establishment of disease models and for treating degenerative diseases. However,
the extremely low survival level of dissociated hESCs following cryopreservation
is been a tremendous problem to allow for their rapid expansion, genetic
manipulation and future medical applications. In this study, we have aimed to
develop an efficient strategy to improve survival of dissociated hESCs after
cryopreservation. MATERIALS AND METHODS: Human embryonic stem cells (H9 line),
dissociated into single cells, were cryopreserved using the slow-freezing method.
Viable cells and their colony numbers in culture after cryopreservation were
evaluated when treated with protein kinase A inhibitor H89. Western blotting was
carried out to investigate mechanisms of low survival levels of dissociated hESCs
following cryopreservation. Immunofluorescence, reverse transcription-polymerase
chain reaction (RT-PCR), in vitro and in vivo differentiation were performed to
testify to pluripotency and differentiation ability of hte cryopreserved cells
treated with H89. RESULTS: H89 significantly improved survival level of
dissociated hESCs after cryopreservation through ROCK inhibition. H89-treated
cells still maintained their pluripotency and differentiation capacity.
CONCLUSIONS: This new approach for cryopreservation of single hESCs, using H89,
can promote potential use of hESCs in regenerative medicine in the future.
PMID- 27484642
TI - The impact of phylogenetic dating method on interpreting trait evolution: a case
study of Cretaceous-Palaeogene eutherian body-size evolution.
AB - The fossil record of the earliest Cenozoic contains the first large-bodied
placental mammals. Several evolutionary models have been invoked to explain the
transition from small to large body sizes, but methods for determining
evolutionary mode of trait change depend on input from tree topology and
divergence dates. Different dating methods may therefore affect inference of
evolutionary model. Here, we fit models of body mass evolution onto dated
phylogenies of Cretaceous and Palaeogene mammals, comparing the effect of dating
method on interpretation of evolutionary model. Among traditional
palaeontological dating approaches, an Ornstein-Uhlenbeck model with high alpha
parameters is recovered as best-fitting when minimum-age dating is used, while
branch-sharing methods are highly sensitive to topology. Release or release
radiate models are preferred when Bayesian fossilized birth-death method is used,
but when using stochastic cal3 dating of trees, a model of increased evolutionary
rate without a release in constraint at the Cretaceous-Palaeogene boundary has
highest support. These results demonstrate unambiguously that choice of dating
method is critical for interpretation of continuous trait evolution, and that
care must therefore be taken to consider these effects in macroevolutionary
studies.
PMID- 27484643
TI - Male-biased sex allocation in ageing parents; a longitudinal study in a long
lived seabird.
AB - Optimal sex allocation is frequency-dependent, but senescence may cause behaviour
at old age to be suboptimal. We investigated whether sex allocation changes with
parental age, using 16 years of data comprising more than 2500 molecularly sexed
offspring of more than 600 known-age parents in common terns (Sterna hirundo),
slightly sexually size-dimorphic seabirds. We decomposed parental age effects
into within-individual change and sex allocation-associated selective
(dis)appearance. Individual parents did not differ consistently in sex
allocation, but offspring sex ratios at fledging changed from female- to male
biased as parents aged. Sex ratios at hatching were not related to parental age,
suggesting sons to outperform daughters after hatching in broods of old parents.
Our results call for the integration of sex allocation theory with theory on
ageing and demography, as a change in sex allocation with age per se will cause
the age structure of a population to affect the frequency-dependent benefits and
the age-specific strength of selection on sex allocation.
PMID- 27484644
TI - Exoskeletons and economics: indoor arthropod diversity increases in affluent
neighbourhoods.
AB - In urban ecosystems, socioeconomics contribute to patterns of biodiversity. The
'luxury effect', in which wealthier neighbourhoods are more biologically diverse,
has been observed for plants, birds, bats and lizards. Here, we used data from a
survey of indoor arthropod diversity (defined throughout as family-level
richness) from 50 urban houses and found that house size, surrounding vegetation,
as well as mean neighbourhood income best predict the number of kinds of
arthropods found indoors. Our finding, that homes in wealthier neighbourhoods
host higher indoor arthropod diversity (consisting of primarily non-pest
species), shows that the luxury effect can extend to the indoor environment. The
effect of mean neighbourhood income on indoor arthropod diversity was
particularly strong for individual houses that lacked high surrounding vegetation
ground cover, suggesting that neighbourhood dynamics can compensate for local
choices of homeowners. Our work suggests that the management of neighbourhoods
and cities can have effects on biodiversity that can extend from trees and birds
all the way to the arthropod life in bedrooms and basements.
PMID- 27484645
TI - Aposematism: balancing salience and camouflage.
AB - Aposematic signals are often characterized by high conspicuousness. Larger and
brighter signals reinforce avoidance learning, distinguish defended from
palatable prey and are more easily memorized by predators. Conspicuous
signalling, however, has costs: encounter rates with naive, specialized or
nutritionally stressed predators are likely to increase. It has been suggested
that intermediate levels of aposematic conspicuousness can evolve to balance
deterrence and detectability, especially for moderately defended species. The
effectiveness of such signals, however, has not yet been experimentally tested
under field conditions. We used dough caterpillar-like baits to test whether
reduced levels of aposematic conspicuousness can have survival benefits when
predated by wild birds in natural conditions. Our results suggest that, when
controlling for the number and intensity of internal contrast boundaries
(stripes), a reduced-conspicuousness aposematic pattern can have a survival
advantage over more conspicuous signals, as well as cryptic colours. Furthermore,
we find a survival benefit from the addition of internal contrast for both high
and low levels of conspicuousness. This adds ecological validity to evolutionary
models of aposematic saliency and the evolution of honest signalling.
PMID- 27484646
TI - Survival is linked with reaction time and spatial memory in African striped mice.
AB - Studying the association between fitness and cognition in free-living animals is
a fundamental step in the elucidation of the evolution of cognition. We assessed
whether survival until the onset of the breeding season was related to reaction
time or spatial memory in the African striped mouse Rhabdomys pumilio, a rodent
that has to survive summer drought before breeding. We tested a total of 90
individuals at the beginning of summer. Female survival was related to a faster
response to predation stimuli. Male survival increased with greater spatial
memory, possibly because it is important for males to remember the configuration
of the environment during dispersal. This study revealed that individual
variation in reaction time and spatial memory can be related to survival
probability, which is important for understanding the selection pressures acting
on basic cognitive traits.
PMID- 27484647
TI - Partially incorrect fossil data augment analyses of discrete trait evolution in
living species.
AB - Ancestral state reconstruction of discrete character traits is often vital when
attempting to understand the origins and homology of traits in living species.
The addition of fossils has been shown to alter our understanding of trait
evolution in extant taxa, but researchers may avoid using fossils alongside
extant species if only few are known, or if the designation of the trait of
interest is uncertain. Here, I investigate the impacts of fossils and incorrectly
coded fossils in the ancestral state reconstruction of discrete morphological
characters under a likelihood model. Under simulated phylogenies and data,
likelihood-based models are generally accurate when estimating ancestral node
values. Analyses with combined fossil and extant data always outperform analyses
with extant species alone, even when around one quarter of the fossil information
is incorrect. These results are especially pronounced when model assumptions are
violated, such as when there is a trend away from the root value. Fossil data are
of particular importance when attempting to estimate the root node character
state. Attempts should be made to include fossils in analysis of discrete traits
under likelihood, even if there is uncertainty in the fossil trait data.
PMID- 27484648
TI - Trait-mediated indirect interactions of ant shape on the attack of caterpillars
and fruits.
AB - Mainly owing to their high diversity and abundance, ants are formidable as
predators and defenders of foliage. Consequently, ants can exclude both
invertebrate and vertebrate activity on plants via direct and indirect
interactions as already shown in many previous studies. Here we present empirical
evidence that objects resembling ant shape on dummy caterpillars were able to
repel visually oriented predators. Moreover, we also show that rubber ants on
dummy fruits can repel potential fruit dispersers. Our results have direct
implications on the ecological and evolutionary dynamics of interactions in ant
based systems, as ant presence could affect the fitness of its partners. In
short, our study highlights the importance of visual cues in interspecific
interactions and opens a new way to study the effects of ant presence to test
ecological and evolutionary hypotheses.
PMID- 27484649
TI - Bioturbation enhances the aerobic respiration of lake sediments in warming lakes.
AB - While lakes occupy less than 2% of the total surface of the Earth, they play a
substantial role in global biogeochemical cycles. For instance, shallow lakes are
important sites of carbon metabolism. Aerobic respiration is one of the important
drivers of the carbon metabolism in lakes. In this context, bioturbation impacts
of benthic animals (biological reworking of sediment matrix and ventilation of
the sediment) on sediment aerobic respiration have previously been
underestimated. Biological activity is likely to change over the course of a year
due to seasonal changes of water temperatures. This study uses microcosm
experiments to investigate how the impact of bioturbation (by Diptera,
Chironomidae larvae) on lake sediment respiration changes when temperatures
increase. While at 5 degrees C, respiration in sediments with and without
chironomids did not differ, at 30 degrees C sediment respiration in microcosms
with 2000 chironomids per m(2) was 4.9 times higher than in uninhabited
sediments. Our results indicate that lake water temperature increases could
significantly enhance lake sediment respiration, which allows us to better
understand seasonal changes in lake respiration and carbon metabolism as well as
the potential impacts of global warming.
PMID- 27484650
TI - Early diving behaviour in juvenile penguins: improvement or selection processes.
AB - The early life stage of long-lived species is critical to the viability of
population, but is poorly understood. Longitudinal studies are needed to test
whether juveniles are less efficient foragers than adults as has been
hypothesized. We measured changes in the diving behaviour of 17 one-year-old king
penguins Aptenodytes patagonicus at Crozet Islands (subantartic archipelago)
during their first months at sea, using miniaturized tags that transmitted diving
activity in real time. We also equipped five non-breeder adults with the same
tags for comparison. The data on foraging performance revealed two groups of
juveniles. The first group made shallower and shorter dives that may be
indicative of early mortality while the second group progressively increased
their diving depths and durations, and survived the first months at sea. This
surviving group of juveniles required the same recovery durations as adults, but
typically performed shallower and shorter dives. There is thereby a relationship
between improved diving behaviour and survival in young penguins. This long
period of improving diving performance in the juvenile life stage is potentially
a critical period for the survival of deep avian divers and may have implications
for their ability to adapt to environmental change.
PMID- 27484651
TI - Association of interleukin-16 polymorphisms with disease progression and
susceptibility in endometriosis.
AB - Interleukin-16 (IL-16) is a multifunctional pro-inflammatory cytokine that was
previously found in association with complex disorders, and it is now cleared
that this cytokine plays a critical role in regulation of cellular functions such
as homoeostasis. Due to the complexity of endometriosis and its resemblance to
cancer, we designed present case-control study to determine the effects of
genetic polymorphisms of the human IL-16 gene on Iranian women's susceptibility
to endometriosis. A total of 126 patients with endometriosis (stages I-IV) and
144 healthy women as control group were recruited to the study. We genotyped four
single nucleotide polymorphisms of IL-16 gene (rs11556218 T>G, rs4778889 T>C,
rs4072111 C>T and rs1131445 C>T). Genotyping was performed using PCR and
restriction fragment length polymorphism. Our results showed that genotype
distribution in two exonic polymorphisms including rs11556218 and rs4072111 was
significantly different between Endometriosis patients and healthy individuals (P
< 0.05). We have also found an association between rs4072111 and rs1131445 with
progression to the severe stages (III-IV) of endometriosis (P < 0.05). Finally,
we may conclude that IL-16 gene polymorphisms are highly associated with
increased risk of endometriosis and could be considered as a susceptibility
factor for endometriosis.
PMID- 27484653
TI - The "Other" in Ourselves: Exploring the Educational Power of the Humanities and
Arts.
PMID- 27484652
TI - Have adults lost their sense of play? An observational study of the social
dynamics of physical (in)activity in German and Hawaiian leisure settings.
AB - BACKGROUND: Physical inactivity is one of the biggest health problems nowadays.
Recent research shows that socio-cultural barriers to physical activity are
mostly related to modern lifestyles. However, there is a lack of research on how
social and group dynamics influence engagement in physical activity. Furthermore,
there are few cross-cultural studies that have compared the social dynamics of
(in)activity in different cultural settings. This paper therefore aims to analyse
how social group dynamics influence physical activity and inactivity in informal
social environments and whether physical activity is influenced by the socio
cultural settings. METHODS: The paper presents the qualitative data collected
within a covert participant observation study. Data was collected by keeping
observational notes in order to record typical, regular patterns regarding
physical (in)activity related behaviour of groups at an artificial open air
swimming pool in Germany and a natural pond in Hawai'i. The data collection
period was eight and a half months. Data was interpreted based on constant
comparative analysis in order to identify most generative patterns in the field
notes. RESULTS: Group structures appear to play a significant role regarding the
activity of the group members. In this study, we identified four key factors that
influence group based physical activity: 1) Physical activity seems to be a group
disturbing behaviour particularly in larger groups of adults; 2) Physical
activity appears to be more functional and less joyful in adults than in
children; 3) Group activity is influenced by (in)activity anchors, including
'domestication' of a group's site, obesity, and controlling parents. 4) Physical
activity is to a certain extent socially contagious, particularly with regard to
playful activities. CONCLUSIONS: Successful promotion of physical activity should
target the social structures of inactive individuals' groups. In this regard, one
of the main problems is that fun and wellbeing, as very important targets of
public health strategies for the adult population, appear not to be compatible
with physical activity. Developing strategies to reframe physical activity rather
as 'fun' and less as functional may be one way to engage inactive individuals in
physical activity in leisure settings.
PMID- 27484654
TI - State of rare disease management in Southeast Asia.
AB - BACKGROUND: Rare diseases, also referred to as orphan diseases, are characterised
by their low prevalence with majority of them are chronically debilitating and
life threatening. Given the low prevalence and the widely dispersed but very
small patient base for each disease, there may often be a disproportion in the
availability of treatments and resources to manage patients, spur research and
train experts. This is especially true in Southeast Asian countries that are
currently in the process of implementing or revising their universal health
coverage schemes. This paper aims to examine the status of rare disease
management in Southeast Asian countries. It will serve as the basis for a more
active discussion on how countries in the region can address an under-recognised
rare disease burden and enhance national and regional capacities. METHODS: The
study consists of literature reviews and key stakeholders interviews in six focus
countries, including the Philippines, Singapore, Malaysia, Indonesia, Vietnam,
and Thailand and five countries as best practice, comprising of France, Canada,
Australia, Taiwan, and South Korea. Rare disease management initiatives across
each country were examined based on the World Health Organization's framework for
action in strengthening health systems. RESULTS: The results suggest rare disease
management remains challenging across Southeast Asia, as many of the focus
countries face fundamental issues from basic healthcare systems to funding.
Nonetheless, there are substantial improvement opportunities, including
leveraging best practices from around the world and organising a multi
stakeholder and regional approach and strategy. CONCLUSIONS: Southeast Asian
countries have made significant progress in the management of rare disease, but
there remain key areas for substantial development opportunities.
PMID- 27484655
TI - Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment
with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems.
AB - Direct-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective
antiviral activity with few side effects. However, the selection of DAA
resistance mutants is a growing problem that needs to be resolved. In contrast,
miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and
a high barrier to drug resistance. In the present study, we evaluated three DAAs
(simeprevir, daclatasvir, and sofosbuvir) in combination with anti-miR-122
treatment against HCV genotype 1a in cell cultures. We found that combination
treatments with anti-miR-122 and a DAA had additive or synergistic antiviral
effects. The EC50 values of simeprevir in simeprevir-resistant mutants were
significantly decreased by combining simeprevir with anti-miR-122. A similar
reduction in EC50 in daclatasvir-resistant mutants was achieved by combining
daclatasvir with anti-miR-122. Combination treatment in HCV-replicating cells
with DAA and anti-miR-122 sharply reduced HCV RNA amounts. Conversely, DAA single
treatment with simeprevir or daclatasvir reduced HCV RNA levels initially, but
the levels later rebounded. DAA-resistant mutants were less frequently observed
in combination treatments than in DAA single treatments. In summary, the addition
of miR-122 antagonism to DAA single treatments had additive or synergistic
antiviral effects and helped to efficiently suppress HCV replication and the
emergence of DAA-resistant mutants.
PMID- 27484656
TI - The Cardiac Conduction System: Generation and Conduction of the Cardiac Impulse.
AB - In this article, the authors outline the key components behind the automated
generation of the cardiac impulses and the effect these impulses have on cardiac
myocytes. Also, a description of the key components of the normal cardiac
conduction system is provided, including the sinoatrial node, the
atrioventricular node, the His bundle, the bundle branches, and the Purkinje
network. Finally, an outline of how each stage of the cardiac conduction system
is represented on the electrocardiogram is described, allowing the reader of the
electrocardiogram to translate background information about the normal cardiac
conduction system to everyday clinical practice.
PMID- 27484657
TI - The Normal Electrocardiogram: Resting 12-Lead and Electrocardiogram Monitoring in
the Hospital.
AB - The electrocardiogram (ECG) is a well-established diagnostic tool extensively
used in clinical settings. Knowledge of cardiac rhythm and mastery of cardiac
waveform interpretation are fundamental for intensive care nurses. Recognition of
the normal findings for the 12-lead ECG and understanding the significance of
changes from baseline in continuous cardiac monitoring are essential steps toward
ensuring safe patient care. This article highlights historical developments in
electrocardiography, describes the normal resting 12-lead ECG, and discusses the
need for continuous cardiac monitoring. In addition, future directions for the
ECG are explored briefly.
PMID- 27484658
TI - Bradyarrhythmias: Clinical Presentation, Diagnosis, and Management.
AB - Bradyarrhythmias are common clinical findings consisting of physiologic and
pathologic conditions (sinus node dysfunction and atrioventricular [AV]
conduction disturbances). Bradyarrhythmias can be benign, requiring no treatment;
however, acute unstable bradycardia can lead to cardiac arrest. In patients with
confirmed or suspected bradycardia, a thorough history and physical examination
should include possible causes of sinoatrial node dysfunction or AV block.
Management of bradycardia is based on the severity of symptoms, the underlying
causes, presence of potentially reversible causes, presence of adverse signs, and
risk of progression to asystole. Pharmacologic therapy and/or pacing are used to
manage unstable or symptomatic bradyarrhythmias.
PMID- 27484659
TI - Paroxysmal Supraventricular Tachycardia: Pathophysiology, Diagnosis, and
Management.
AB - Paroxysmal supraventricular tachycardia (PSVT) is a well-known and thoroughly
studied clinical syndrome, characterized by regular tachycardia rhythm with
sudden onset and abrupt termination. Most patients present with palpitations and
dizziness, and their electrocardiogram demonstrates a narrow QRS complex and
regular tachycardia with hidden or inverted P waves. PSVT is caused by re-entry
due to the presence of inhomogeneous, accessory, or concealed conducting
pathways. Hemodynamically stable patients are treated by vagal maneuvers,
intravenous adenosine, diltiazem, or verapamil, hemodynamically unstable patients
are treated by cardioversion. Patients with symptomatic and recurrent PSVT can be
treated with long-term drug treatment or catheter ablation.
PMID- 27484660
TI - Ventricular Tachycardias: Characteristics and Management.
AB - Ventricular tachycardias include ventricular tachycardia, ventricular
fibrillation, and torsades de pointes; although these rhythms may be benign and
asymptomatic, others may be life threatening and lead to increased morbidity and
mortality. To optimize patient outcomes, ventricular tachycardias need to be
rapidly diagnosed and managed, and often the electrocardiogram (ECG) is the first
and only manifestation of a cardiac defect. Understanding of the initial
electrocardiographic pattern and subsequent changes can lead to early
intervention and an improved outcome. This article describes mechanisms, ECG
characteristics, and management of ventricular tachycardias.
PMID- 27484662
TI - Acute Coronary Syndrome and ST Segment Monitoring.
AB - Acute coronary syndrome (ACS) is caused by a critical obstruction of a coronary
artery because of atherosclerotic coronary artery disease. Three specific
conditions are included: ST elevation myocardial infarction, non-ST elevation
myocardial infarction, and unstable angina. The ST segment on the
electrocardiogram is a sensitive and specific marker of myocardial ischemia and
infarction; however, ST segment deviation is regional not global, thus the ECG
lead must be placed over the affected region of the myocardium. This article
describes ACS and infarction and the use of ST segment monitoring to detect these
conditions.
PMID- 27484661
TI - Cardiac Monitoring in the Emergency Department.
AB - Patients present to the emergency department (ED) with a wide range of complaints
and ED clinicians are responsible for identifying which conditions are life
threatening. Cardiac monitoring strategies in the ED include, but are not limited
to, 12-lead electrocardiography and bedside cardiac monitoring for arrhythmia and
ischemia detection as well as QT-interval monitoring. ED nurses are in a unique
position to incorporate cardiac monitoring into the early triage and risk
stratification of patients with cardiovascular emergencies to optimize patient
management and outcomes.
PMID- 27484663
TI - Basic Cardiac Electrophysiology and Common Drug-induced Arrhythmias.
AB - Drugs can be a double-edged sword, providing the benefit of symptom alleviation
and disease modification but potentially causing harm from adverse cardiac
arrhythmic events. Proarrhythmia is the ability of a drug to cause an arrhythmia,
the number one reason for drugs to be withdrawn from the patient. Drug-induced
arrhythmias are defined as the production of de novo arrhythmias or aggravation
of existing arrhythmias, as a result of previous or concomitant pharmacologic
treatment. This review summarizes normal cardiac cell and tissue functioning and
provides an overview of drugs that effect cardiac repolarization and the adverse
effects of commonly administered antiarrhythmics.
PMID- 27484664
TI - Arrhythmias and Cardiac Bedside Monitoring in the Neonatal Intensive Care Unit.
AB - Cardiac physiology is unique in neonates and infants; there are several
physiologic changes that occur in the first weeks of life. Important changes can
be captured on the bedside monitor and provide vital data in a noninvasive way to
providers. The importance of diligent observation cannot be overstated. Bedside
monitoring has improved in the last decade, which has enhanced the ability to
detect changes in heart rates and rhythms. The purpose here is to review cardiac
physiology, describe those arrhythmias able to be observed on bedside monitors,
and highlight heart rate changes that can be early signs of sepsis.
PMID- 27484665
TI - In-Hospital Cardiac Arrest: An Update on Pulseless Electrical Activity and
Asystole.
AB - Nonshockable rhythms, including pulseless electrical activity (PEA) and asystole,
precede more than 70% of in-hospital cardiac arrests (I-HCA). Compared with
shockable rhythms (ventricular fibrillation and ventricular tachycardia),
nonshockable rhythms have higher mortality and morbidity. Therefore,
investigating the underlying mechanisms of these arrhythmias to improve the
quality of care and outcome for patients who suffer cardiac arrest is a priority.
As the first responders to I-HCA, nurses must have the proper knowledge and
training to provide timely and efficient cardiopulmonary resuscitation therapy.
This article provides an overview of nonshockable cardiac arrhythmias preceding I
HCA as a means of addressing the gap between science and clinical practice.
PMID- 27484666
TI - Cardiac Arrhythmias.
PMID- 27484667
TI - Prognostic enrichment design in clinical trials for autosomal dominant polycystic
kidney disease: the HALT-PKD clinical trial.
AB - Background: Patients with mild autosomal dominant polycystic kidney disease
(ADPKD) are less likely to be informative in randomized clinical trials (RCTs).
We previously developed an imaging classification of ADPKD (typical diffuse cyst
distribution Class 1A-E and atypical cyst distribution Class 2) for prognostic
enrichment design in RCTs. We investigated whether using this classification
would have increased the power to detect a beneficial treatment effect of
rigorous blood pressure (BP) control on HALT-PKD participants with early disease
(Study A). Methods: Post hoc analysis of the early disease HALT-PKD study, an RCT
that studied the effect of rigorous versus standard BP control on rates of total
kidney volume (TKV) increase and estimated glomerular filtration rate (eGFR)
decline in ADPKD patients with eGFR >60 mL/min/1.73 m2. Results: Five hundred and
fifty-one patients were classified by two observers (98.2% agreement) into Class
1A (6.2%), 1B (20.3%), 1C (34.1%), 1D (22.1%), 1E (11.8%) and 2 (5.4%). The TKV
increase and eGFR decline became steeper from Class 1A through 1E. Rigorous BP
control had been shown to be associated with slower TKV increase, without a
significant overall effect on the rate of eGFR decline (faster in the first 4
months and marginally slower thereafter). Merging Classes 1A and 2 (lowest
severity), 1B and 1C (intermediate severity) and 1D and 1E (highest severity)
detected stronger beneficial effects on TKV increase and eGFR decline in Class 1D
and E with a smaller number of patients. Conclusions: Strategies for prognostic
enrichment, such as image classification, should be used in the design of RCTs
for ADPKD to increase their power and reduce their cost.
PMID- 27484668
TI - Fermentative production of high titer gluconic and xylonic acids from corn stover
feedstock by Gluconobacter oxydans and techno-economic analysis.
AB - High titer gluconic acid and xylonic acid were simultaneously fermented by
Gluconobacter oxydans DSM 2003 using corn stover feedstock after dry dilute
sulfuric acid pretreatment, biodetoxification and high solids content hydrolysis.
Maximum sodium gluconate and xylonate were produced at the titer of 132.46g/L and
38.86g/L with the overall yield of 97.12% from glucose and 90.02% from xylose,
respectively. The drawbacks of filamentous fungus Aspergillus niger including
weak inhibitor tolerance, large pellet formation and no xylose utilization were
solved by using the bacterium strain G. oxydans. The obtained sodium
gluconate/xylonate product was highly competitive as cement retarder additive to
the commercial product from corn feedstock. The techno-economic analysis (TEA)
based on the Aspen Plus modeling was performed and the minimum sodium
gluconate/xylonate product selling price (MGSP) was calculated as $0.404/kg. This
study provided a practical and economic competitive process of lignocellulose
utilization for production of value-added biobased chemicals.
PMID- 27484669
TI - Boosting dark fermentation with co-cultures of extreme thermophiles for
biohythane production from garden waste.
AB - Proof of principle of biohythane and potential energy production from garden
waste (GW) is demonstrated in this study in a two-step process coupling dark
fermentation and anaerobic digestion. The synergistic effect of using co-cultures
of extreme thermophiles to intensify biohydrogen dark fermentation is
demonstrated using xylose, cellobiose and GW. Co-culture of Caldicellulosiruptor
saccharolyticus and Thermotoga maritima showed higher hydrogen production yields
from xylose (2.7+/-0.1molmol(-1) total sugar) and cellobiose (4.8+/-0.3molmol(-1)
total sugar) compared to individual cultures. Co-culture of extreme thermophiles
C. saccharolyticus and Caldicellulosiruptor bescii increased synergistically the
hydrogen production yield from GW (98.3+/-6.9Lkg(-1) (VS)) compared to individual
cultures and co-culture of T. maritima and C. saccharolyticus. The biochemical
methane potential of the fermentation end-products was 322+/-10Lkg(-1) (CODt).
Biohythane, a biogas enriched with 15% hydrogen could be obtained from GW,
yielding a potential energy generation of 22.2MJkg(-1) (VS).
PMID- 27484670
TI - Mitigation of carbon dioxide by oleaginous microalgae for lipids and pigments
production: Effect of light illumination and carbon dioxide feeding strategies.
AB - Oleaginous microalgae Nannochloropsis sp. was selected as potential strain for
CO2 mitigation into lipids and pigments. The synergistic effects of light
intensity and photoperiod were evaluated to provide the adequate light energy for
this strain. The saturation light intensity was 60MUmol.photon.m(-2)s(-1). With
full illumination, the biomass obtained was 0.850+/-0.16g.L(-1) with a lipid
content of 44.7+/-1.2%. The pigments content increased with increasing light
energy supply. Three main operating factors including initial cell concentration,
CO2 content and gas flow rate were optimized through Response Surface
Methodology. The feedings with low CO2 content at high gas flow rate gave the
maximum biomass but with low lipid content. After optimization, the biomass and
lipid production were increased up to 1.30+/-0.103g.L(-1) and 0.515+/-0.010g.L(
1), respectively. The CO2 fixation rate was as high as 0.729+/-0.04g.L(-1)d(-1).
The fatty acids of Nannochloropsis sp. lipids were mainly C16-C18 indicating its
potential use as biodiesel feedstocks.
PMID- 27484671
TI - Study on the bio-methane yield and microbial community structure in enzyme
enhanced anaerobic co-digestion of cow manure and corn straw.
AB - The use of enzymes to improve anaerobic co-digestion (AcoD) of cow manure and
corn straw was explored in this study, including cellulase pretreatment and
direct additions of amylase and protease. The effects of enzymes on microbial
community structure were investigated though PCR-DGGE method. Results showed that
AcoD with amylase achieved the highest methane yield of 377.63ml.CH4/g.VS, which
was an increase of 110.79%. The methane increment consumed the amylase of
4.18*10(-5)g/ml.CH4. Enzymes mainly affected the bacteria in the hydrolysis stage
rather than the bacteria in the hydrogenesis and acetogenesis stage and the
archaea in the methanogenesis stage. However, the experimental results
demonstrated that enzymes had no negative influence on microbial communities; the
predominant microbial communities were similar. Therefore, AcoD with amylase was
an effective way to improve the bio-methane yield of cow manure and corn straw.
PMID- 27484672
TI - Butanol production in acetone-butanol-ethanol fermentation with in situ product
recovery by adsorption.
AB - Activated carbon Norit ROW 0.8, zeolite CBV901, and polymeric resins Dowex
Optipore L-493 and SD-2 with high specific loadings and partition coefficients
were studied for n-butanol adsorption. Adsorption isotherms were found to follow
Langmuir model, which can be used to estimate the amount of butanol adsorbed in
acetone-butanol-ethanol (ABE) fermentation. In serum-bottle fermentation with in
situ adsorption, activated carbon showed the best performance with 21.9g/L of
butanol production. When operated in a fermentor, free- and immobilized-cell
fermentations with adsorption produced 31.6g/L and 54.6g/L butanol with
productivities of 0.30g/L.h and 0.45g/L.h, respectively. Thermal desorption
produced a condensate containing ~167g/L butanol, which resulted in a highly
concentrated butanol solution of ~640g/L after spontaneous phase separation. This
in situ product recovery process with activated carbon is energy efficient and
can be easily integrated with ABE fermentation for n-butanol production.
PMID- 27484673
TI - Interplay between up-regulation of cytochrome-c-oxidase and hemoglobin
oxygenation induced by near-infrared laser.
AB - Photobiomodulation, also known as low-level laser/light therapy (LLLT), refers to
the use of red-to-near-infrared light to stimulate cellular functions for
physiological or clinical benefits. The mechanism of LLLT is assumed to rely on
photon absorption by cytochrome c oxidase (CCO), the terminal enzyme in the
mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy
metabolism. In this study, we used broadband near-infrared spectroscopy (NIRS) to
measure the LLLT-induced changes in CCO and hemoglobin concentrations in human
forearms in vivo. Eleven healthy participants were administered with 1064-nm
laser and placebo treatments on their right forearms. The spectroscopic data were
analyzed and fitted with wavelength-dependent, modified Beer-Lambert Law. We
found that LLLT induced significant increases of CCO concentration (Delta[CCO])
and oxygenated hemoglobin concentration (Delta[HbO]) on the treated site as the
laser energy dose accumulated over time. A strong linear interplay between
Delta[CCO] and Delta[HbO] was observed for the first time during LLLT, indicating
a hemodynamic response of oxygen supply and blood volume closely coupled to the
up-regulation of CCO induced by photobiomodulation. These results demonstrate the
tremendous potential of broadband NIRS as a non-invasive, in vivo means to study
mechanisms of photobiomodulation and perform treatment evaluations of LLLT.
PMID- 27484674
TI - Parenting while living with advanced cancer: A qualitative study.
AB - BACKGROUND: Patients with advanced cancer who have dependent children are an
important population with a life-limiting illness and high levels of
psychological distress. Few studies have addressed the experience of being a
parent with advanced cancer and their potential palliative needs. AIM: To
describe the experience of living with advanced cancer as a parent, including
illness experience, parental concerns, and treatment decision making and to
explore whether these experiences differ by their functional status. DESIGN: We
conducted a cross-sectional, qualitative study using in-depth, semi-structured
interviews. Data were analyzed using thematic content analysis. SETTING AND
PARTICIPANTS: A total of 42 participants with metastatic cancer and with at least
one child under the age of 18 years were recruited from a comprehensive cancer
center. 25 participants were rated as having high functional status (the Eastern
Cooperative Oncology Group (ECOG) Performance Status Scale = 0-1) and 17 with low
functional status (ECOG=2-4). RESULTS: We identified four themes regarding the
experience of being a parent with advanced cancer: (1) parental concerns about
the impact of their illness and death on their children, (2) "missing out" and
losses of parental role and responsibilities, (3) maintaining parental
responsibilities despite life-limiting illness, and (4) parental identity
influencing decision making about treatment. Parental functional status
influenced not only physical responsibilities but also intensified parenting
psychological concerns. CONCLUSION: Parents with metastatic cancer may have
unique palliative care needs as they experience parenting concerns while managing
the psychological and physical demands of advanced cancer.
PMID- 27484675
TI - Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative
Vosaroxin: A New Therapeutic Agent for Acute Myeloid Leukemia.
AB - Vosaroxin is a first-in-class anticancer quinolone derivative that targets
topoisomerase II and induces site-selective double-strand breaks in DNA, leading
to tumor cell apoptosis. Vosaroxin has chemical and pharmacologic characteristics
distinct from other topoisomerase II inhibitors due to its quinolone scaffold.
The efficacy and safety of vosaroxin in combination with cytarabine were
evaluated in patients with relapsed/refractory acute myeloid leukemia (AML) in a
phase III, randomized, multicenter, double-blind, placebo-controlled study
(VALOR). In this study, the addition of vosaroxin produced a 1.4-month
improvement in median overall survival (OS; 7.5 months with vosaroxin/cytarabine
vs. 6.1 months with placebo/cytarabine; hazard ratio [HR] 0.87, 95 % confidence
interval [CI] 0.73-1.02; unstratified log-rank p [Formula: see text] 0.061;
stratified log-rank p [Formula: see text]0.024), with the greatest OS benefit
observed in patients >=60 years of age (7.1 vs. 5.0 months; HR 0.75, 95 % CI 0.62
0.92; p [Formula: see text]0.003) and patients with early relapse (6.7 vs. 5.2
months; HR 0.77, 95 % CI 0.59-1.00; p [Formula: see text] 0.039), two AML patient
groups that typically have poor prognosis. Here we review the chemical and
pharmacologic properties of vosaroxin, how these properties are distinct from
those of currently available topoisomerase II inhibitors, how they may contribute
to the efficacy and safety profile observed in the VALOR trial, and the status of
clinical development of vosaroxin for treatment of AML.
PMID- 27484676
TI - Klokwerk + study protocol: An observational study to the effects of night-shift
work on body weight and infection susceptibility and the mechanisms underlying
these health effects.
AB - BACKGROUND: Night-shift work may cause severe disturbances in the worker's
circadian rhythm, which has been associated with the onset of health problems and
diseases. As a substantial part of the workforce is exposed to night-shift work,
harmful aspects of night-shift work should not be overlooked. The aim of the
Klokwerk + study is to study the effects of night-shift work on body weight and
infection susceptibility and the mechanisms underlying these health effects.
First, we will study the relation between night-shift work exposure and body
weight and between night-shift work exposure and infection susceptibility.
Second, we will examine the mechanisms linking night-shift work exposure to body
weight and infection susceptibility, with a specific focus on sleep, physical
activity, diet, light exposure, vitamin D level, and immunological factors.
Lastly, we will focus on the identification of biomarkers for chronic circadian
disturbance associated with night-shift work. METHODS/DESIGN: The design of this
study is a prospective observational cohort study consisting of 1,960 health care
workers aged 18-65 years. The study population will consist of a group of night
shift workers and an equally sized group of non-night-shift workers. During the
study, there will be two measurement periods. As one of the main outcomes of this
study is infection susceptibility, the measurement periods will take place at
approximately the first (September/October) (T0) and the last month (April/May)
(T1, after 6 months) of the flu season. The measurements will consist of
questionnaires, anthropometric measurements, a smartphone application to
determine infection susceptibility, food diaries, actigraphy, light sensors, and
blood sample analyses. DISCUSSION: The Klokwerk + study will contribute to the
current need for high-quality data on the health effects of night-shift work and
its underlying behavioral and physiological mechanisms. The findings can be the
starting point for the development of interventions that prevent negative health
effects caused by night-shift work. In addition, the identification of biomarkers
indicative of loss of homeostasis due to circadian disturbance may be an
important asset in monitoring the effects of such interventions.
PMID- 27484677
TI - Optimization of Routine Monitoring of Workers Exposed to Plutonium Aerosols.
AB - In case of incidental confinement failure, mixed oxide (MOX) fuel preparation may
expose workers to plutonium aerosols. Due to its potential toxicity, occupational
exposure to plutonium compounds should be kept as low as reasonably achievable.
To ensure the absence of significant intake of radionuclides, workers at risk of
internal contamination are monitored by periodic bioassay planned in a routine
monitoring programme. From bioassay results, internal dose may be estimated.
However, accurate dose calculation relies on known exposure conditions, which are
rarely available when the exposure is demonstrated by routine monitoring only.
Therefore, internal dose calculation is subject to uncertainty from unknown
exposure conditions and from activity measurement variability. The present study
calculates the minimum detectable dose (MDD) for a routine monitoring programme
by considering all plausible conditions of exposure and measurement uncertainty.
The MDD evaluates the monitoring quality and can be used for optimization. Here,
MDDs were calculated for the monitoring of workers preparing MOX fuel. Uncertain
parameters were modelled by probability distributions defined according to
information provided by experts of routine monitoring, of workplace radiological
protection and of bioassay analysis. Results show that the current monitoring is
well adapted to potential exposure. A sensitivity study of MDD highlights high
dependence on exposure condition modelling. Integrating all expert knowledge is
therefore crucial to obtain reliable MDD estimates, stressing the value of a
holistic approach to worker monitoring.
PMID- 27484679
TI - [Osteosynthesis of displaced fractures of the greater tuberosity with the Bamberg
plate].
AB - OBJECTIVE: Internal fixation of displaced fractures of the greater tuberosity
allowing functional aftercare. INDICATIONS: Displaced fractures of the greater
tuberosity >5 mm. Displaced fractures of the greater tuberosity >3 mm in athletes
or overhead workers. Multiply fragmented fractures of the greater tuberosity.
CONTRAINDICATIONS: Displaced 3- or 4-part fractures of the proximal humerus.
Nondisplaced fractures of the greater tuberosity. SURGICAL TECHNIQUE: Exposure of
the fracture of the greater tuberosity by an anterolateral approach. Open
reduction and temporary retention with a Kirschner wire or a "Kugelspiebeta" or
reinforcement of the supraspinatus tendon and distal retention. Bending and
positioning of the Bamberg plate and fixation by conventional or locking screws.
Optional fixation of the rotator cuff to the plate. Exact monitoring of the
implant position using the image intensifier to avoid inadequate distalization of
the greater tuberosity. POSTOPERATIVE MANAGEMENT: Arm sling (e. g. Gilchrist) for
2 weeks. Start passive assisted exercise on postoperative day 1. Movement allowed
up to the pain threshold. Physiotherapeutic treatment to prevent adhesions and
capsular shrinking. RESULTS: In all, 10 patients with displaced fractures of the
greater tuberosity underwent osteosynthesis using the Bamberg plate. After a
follow-up of at least 6 months, a Constant-Murley score of 94.2 points (range 91
98 points) was achieved. The patients' average age was 45.6 years (range 29-68
years).
PMID- 27484678
TI - [Surgical treatment of anterosuperior impingement of the shoulder].
AB - OBJECTIVE: Therapy of intraarticular lesions and elimination of structural risk
factors for those suffering from clinical manifest anterosuperiorer impingement
(ASI) of the shoulder. This includes as a maximum version the arthroscopic repair
of supraspinatus (SST) and subscapularis tendon (SCT) tears with subsequent
subpectoral tenodesis of the long head of the biceps tendon (LBT) and
arthroscopic coracoplasty. INDICATIONS: Clinical manifest anterosuperiorer
impingement of the shoulder with anterior shoulder pain, failed conservative
treatment and clear intraarticular damage in radiological imaging. This involves
in detail lesions of the SST, SCT and damage to the LBT. CONTRAINDICATIONS: Lack
of structural intraarticular lesions or massive osteoarthritis. Persistent
dysfunction of active and passive glenohumeral and scapulathoracal motion, due to
neurologic deficits or stiff shoulder. A hypertrophic or deformed healed coracoid
process is seen as a structural risk factor for suffering from ASI and should be
addressed surgically when causing impingement. SURGICAL TECHNIQUE: Arthroscopic
tenotomy of the LBT with subsequent repair of the SST and SCT. Arthroscopic
coracoplasty if indicated and subpectoral tenodesis of the long head of the
biceps. POSTOPERATIVE MANAGEMENT: No biceps activity and intermittent
immobilization in sling for 6 weeks. Limitation of abduction, flexion and
external rotation for 6 weeks depending on rotator cuff tendon repair. Start of
sport-specific training after 3 months, over-head sports 6 months
postoperatively. RESULTS: The arthroscopic repair of anterosuperior rotator cuff
tears provides reliable results for improvement in function, decreases in pain
and improvement in shoulder scores. The overall rate of adverse events is low.
PMID- 27484680
TI - Total synthesis of teixobactin.
AB - To cope with the global bacterial multidrug resistance, scientific communities
have devoted significant efforts to develop novel antibiotics, particularly those
with new modes of actions. Teixobactin, recently isolated from uncultured
bacteria, is considered as a promising first-in-class drug candidate for clinical
development. Herein, we report its total synthesis by a highly convergent Ser
ligation approach and this strategy allows us to prepare several analogues of the
natural product.
PMID- 27484681
TI - Fluid overload in the ICU: evaluation and management.
AB - BACKGROUND: Fluid overload is frequently found in acute kidney injury patients in
critical care units. Recent studies have shown the relationship of fluid overload
with adverse outcomes; hence, manage and optimization of fluid balance becomes a
central component of the management of critically ill patients. DISCUSSION: In
critically ill patients, in order to restore cardiac output, systemic blood
pressure and renal perfusion an adequate fluid resuscitation is essential.
Achieving an appropriate level of volume management requires knowledge of the
underlying pathophysiology, evaluation of volume status, and selection of
appropriate solution for volume repletion, and maintenance and modulation of the
tissue perfusion. Numerous recent studies have established a correlation between
fluid overload and mortality in critically ill patients. Fluid overload
recognition and assessment requires an accurate documentation of intakes and
outputs; yet, there is a wide difference in how it is evaluated, reviewed and
utilized. Accurate volume status evaluation is essential for appropriate therapy
since errors of volume evaluation can result in either in lack of essential
treatment or unnecessary fluid administration, and both scenarios are associated
with increased mortality. There are several methods to evaluate fluid status;
however, most of the tests currently used are fairly inaccurate. Diuretics,
especially loop diuretics, remain a valid therapeutic alternative. Fluid overload
refractory to medical therapy requires the application of extracorporeal
therapies. In critically ill patients, fluid overload is related to increased
mortality and also lead to several complications like pulmonary edema, cardiac
failure, delayed wound healing, tissue breakdown, and impaired bowel function.
Therefore, the evaluation of volume status is crucial in the early management of
critically ill patients. Diuretics are frequently used as an initial therapy;
however, due to their limited effectiveness the use of continuous renal
replacement techniques are often required for fluid overload treatment.
Successful fluid overload treatment depends on precise assessment of individual
volume status, understanding the principles of fluid management with
ultrafiltration, and clear treatment goals.
PMID- 27484682
TI - Association Between Initial Opioid Prescribing Patterns and Subsequent Long-Term
Use Among Opioid-Naive Patients: A Statewide Retrospective Cohort Study.
AB - BACKGROUND: Long-term efficacy of opioids for non-cancer pain is unproven, but
risks argue for cautious prescribing. Few data suggest how long or how much
opioid can be prescribed for opioid-naive patients without inadvertently
promoting long-term use. OBJECTIVE: To examine the association between initial
opioid prescribing patterns and likelihood of long-term use among opioid-naive
patients. DESIGN: Retrospective cohort study; data from Oregon resident
prescriptions linked to death certificates and hospital discharges. PARTICIPANTS:
Patients filling opioid prescriptions between October 1, 2012, and September 30,
2013, with no opioid fills for the previous 365 days. Subgroup analyses examined
patients under age 45 who did not die in the follow-up year, excluding most
cancer or palliative care patients. MAIN MEASURES: Exposure: Numbers of
prescription fills and cumulative morphine milligram equivalents (MMEs) dispensed
during 30 days following opioid initiation ("initiation month"). OUTCOME:
Proportion of patients with six or more opioid fills during the subsequent year
("long-term users"). KEY RESULTS: There were 536,767 opioid-naive patients who
filled an opioid prescription. Of these, 26,785 (5.0 %) became long-term users.
Numbers of fills and cumulative MMEs during the initiation month were associated
with long-term use. Among patients under age 45 using short-acting opioids who
did not die in the follow-up year, the adjusted odds ratio (OR) for long-term use
among those receiving two fills versus one was 2.25 (95 % CI: 2.17, 2.33).
Compared to those who received < 120 total MMEs, those who received between 400
and 799 had an OR of 2.96 (95 % CI: 2.81, 3.11). Patients initiating with long
acting opioids had a higher risk of long-term use than those initiating with
short-acting drugs. CONCLUSIONS: Early opioid prescribing patterns are associated
with long-term use. While patient characteristics are important, clinicians have
greater control over initial prescribing. Our findings may help minimize the risk
of inadvertently initiating long-term opioid use.
PMID- 27484683
TI - A co-design process developing heuristics for practitioners providing end of life
care for people with dementia.
AB - BACKGROUND: The end of life for someone with dementia can present many challenges
for practitioners; such as, providing care if there are swallowing difficulties.
This study aimed to develop a toolkit of heuristics (rules-of-thumb) to aid
practitioners making end-of-life care decisions for people with dementia.
METHODS: An iterative co-design approach was adopted using a literature review
and qualitative methods, including; 1) qualitative interviews and focus groups
with family carers and 2) focus groups with health and care professionals. Family
carers were recruited from a national charity, purposively sampling those with
experience of end-of-life care for a person with dementia. Health and care
professionals were purposively sampled to include a broad range of expertise
including; general practitioners, palliative care specialists, and geriatricians.
A co-design group was established consisting of health and social care experts
and family carers, to synthesise the findings from the qualitative work and
produce a toolkit of heuristics to be tested in practice. RESULTS: Four broad
areas were identified as requiring complex decisions at the end of life; 1)
eating/swallowing difficulties, 2) agitation/restlessness, 3) ending life
sustaining treatment, and 4) providing "routine care" at the end of life. Each
topic became a heuristic consisting of rules arranged into flowcharts.
Eating/swallowing difficulties have three rules; ensuring eating/swallowing
difficulties do not come as a surprise, considering if the situation is an
emergency, and considering 'comfort feeding' only versus time-trialled artificial
feeding. Agitation/restlessness encourages a holistic approach, considering the
environment, physical causes, and the carer's wellbeing. Ending life-sustaining
treatment supports practitioners through a process of considering the benefits of
treatment versus quality-of-life and comfort. Finally, a heuristic on providing
routine care such as bathing, prompts practitioners to consider adapting the
delivery of care, in order to promote comfort and dignity at the end of life.
CONCLUSIONS: The heuristics are easy to use and remember, offering a novel
approach to decision making for dementia end-of-life care. They have the
potential to be used alongside existing end-of-life care recommendations, adding
more readily available practical assistance. This is the first study to
synthesise experience and existing evidence into easy-to-use heuristics for
dementia end-of-life care.
PMID- 27484685
TI - Circulating ferritin concentrations are differentially associated with serum
adipokine concentrations in Japanese men and premenopausal women.
AB - PURPOSE: Increased iron storage, as measured by circulating ferritin, has been
linked to an increased risk of various diseases including diabetes. We examined
the association of circulating ferritin with serum adiponectin, leptin, resistin,
plasminogen activator inhibitor-1 (PAI-1), and visfatin levels. METHODS: We
conducted a cross-sectional study among 429 Japanese employees (284 men and 145
premenopausal women, mean age: 42.5 +/- 10.5 years). Serum adipokines were
measured using Luminex suspension bead-based multiplexed array, and serum
ferritin was determined using a chemiluminescence immunoassay. Multivariable
regression analysis was performed to calculate mean concentrations of adipokine
according to the tertile of ferritin concentrations with adjustment for potential
confounders. RESULTS: Leptin and visfatin concentrations increased with
increasing ferritin concentrations in men after multivariable adjustment of
physical activity, smoking, alcohol use, and body mass index (P for trend = 0.02
and 0.01 for leptin and visfatin, respectively). Serum ferritin concentrations
were inversely and significantly associated with adiponectin in women (P for
trend = 0.01). Resistin and PAI-1 were not appreciably associated with ferritin
concentration. CONCLUSIONS: Increased iron storage may be associated with higher
circulating concentrations of leptin and visfatin in men and with lower
concentrations of adiponectin in women.
PMID- 27484686
TI - Risks associated with antipsychotic treatment in pregnancy: Comparative cohort
studies based on electronic health records.
AB - BACKGROUND: Limited information is available on whether antipsychotics prescribed
in pregnancy are associated with increased risks of adverse outcomes. METHODS: We
used electronic health records from pregnant women and their children to examine
risks of adverse maternal and child outcomes in three cohorts of women who: (A)
received antipsychotic treatment in pregnancy (n=416) (B) discontinued
antipsychotic treatment before pregnancy (n=670), and (C) had no records of
antipsychotic treatment before or during pregnancy (n=318,434). Absolute and risk
ratios were estimated and adjusted for health and lifestyle and concomitant
medications. RESULTS: Caesarean section was more common in cohort A (25%) than C
(18%), but non-significant after adjustment for health and lifestyle factors
(Risk Ratio (adj.) 1.09 (95% CI: 0.92, 1.30). Proportion of gestational diabetes
was similar in cohort A (2.6%) and B (2.7%), but lower in A than B after
adjustments (RRadj: 0.43 (0.20, 0.93). Premature birth/low birthweight were more
common in cohort A (10%) than B (4.3%) and C (3.9%), A versus B (RRadj: 2.04
(1.13, 3.67), A versus C (RRadj: 1.43 (0.99, 2.05). Major congenital
malformations were more common in A (3.4%), than B (2.2%) and C (2%). However no
significant difference was observed (A versus B: RRadj: 1.79 (0.72, 4.47) A
versus C RRadj: 1.59 (0.84, 3.00)). Risks estimates were similar for women
prescribed atypical and typical antipsychotics. CONCLUSIONS: Antipsychotic
treatment in pregnancy carries limited risks of adverse pregnancy and birth
outcomes once adjustments have been made for health and lifestyle factors.
PMID- 27484687
TI - Synthesis and characterization of a novel near-infrared fluorescent probe for
applications in imaging A549 cells.
AB - OBJECTIVE: To design and synthesize a novel near-infrared (NIR) fluorescent probe
based on indocyanine Green (ICG), that can be applied in imaging living cells.
RESULTS: A highly fluorescent novel NIR fluorescent probe (IR-793) was
synthesized in two steps. IR-793 had better fluorescence and optical stability
than ICG. In addition, no obvious cytotoxicity effect of IR-793 was observed and
cell viability was above 75% at the maximum concentration (120 nM). IR-793 also
exhibited good performance in imaging living A549 cells. CONCLUSION: IR-793, a
novel NIR fluorescent probe that is stable, low-cost, highly fluorescent and low
cytotoxicity, has been designed and synthesized for imaging living cells.
PMID- 27484684
TI - Vitamin D Deficiency and Rheumatoid Arthritis.
AB - Vitamin D (VitD) is a hormone primarily synthesized in human skin under the
stimulation of ultraviolet radiation. Beyond its endocrine role in bone
metabolism, VitD is endowed with remarkable immunomodulatory properties. The
effects of VitD on the immune system include the enhancement of microbicidal
ability of monocytes/macrophages and the down-modulation of inflammatory
cytokines produced by T lymphocytes. VitD deficiency is involved in many health
problems, including immune-mediated diseases such as autoimmune disorders.
Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease
that compromises the joints, causing cartilage destruction and bone erosion. RA
treatment usually consists of combined therapies that generally suppress the
entire immune response leading to increased susceptibility to infections. This
review describes the main effects of VitD on innate and adaptive immune system
and also VitD status in inflammatory rheumatic diseases such as RA. Despite some
controversies, the majority of reports reinforce the idea that lower VitD levels
correlate with more severe clinical manifestations in RA and other rheumatic
diseases. Therefore, supplementation with VitD to achieve normal serum levels is
worthwhile as an aforethought. Original data concerning the potential
applicability of 1,25-dihydroxyvitamin D3 (VitD3), the active form of vitamin D,
as a tolerogenic adjuvant are also included. In this sense, the effect of VitD3
associated with proteoglycan (PG), which is a specific cartilage antigen, was
tested in the course of experimental arthritis. This association significantly
lowered clinical scores and local histopathological alterations. Even though
local analysis of T cell subsets and cytokine production did not reveal any
difference between the experimental groups, VitD3+PG association significantly
reduced cytokine production by spleen cells. These results suggest that VitD3
played a role as a tolerogenic adjuvant by down-modulating the course of
experimental RA. Considering this tolerogenic effect of VitD3+PG association,
further investigations will reveal its plausible use in human RA.
PMID- 27484688
TI - Silencing of Mythimna separata chitinase genes via oral delivery of in planta
expressed RNAi effectors from a recombinant plant virus.
AB - OBJECTIVES: To evaluate transient expression of RNA interference (RNAi) effectors
in Nicotiana benthamiana plants by using recombinant virus vectors and also oral
delivery of the effectors for silencing of Mythimna separata endogenous gene
expression. RESULTS: Mythimna separata is a serious pest of corn production in
China. To evaluate RNAi approaches to target specific RNAs in M. separate, we
cloned fragments of the M. separata chitinase sequences into a virus vector in
order to produce RNAi effectors during virus infection and replication in plants.
When the infected plants were fed to M. separata, expression levels of target
MseChi1 and MseChi2 genes were down-regulated by 76 and 45 %, respectively, and
sequence-specific siRNAs were detected in recipient insects. RNAi-based silencing
of chitinase genes also led to body weight decreases by 43 %. CONCLUSION: Our
research demonstrates target mRNA knockdown and suggests a promising application
for controlling of M. separata by in planta expression of RNAi effectors using a
recombinant plant virus.
PMID- 27484689
TI - Exosomes derived from tumor cells genetically modified to express Mycobacterium
tuberculosis antigen: a novel vaccine for cancer therapy.
AB - OBJECTIVES: To examine the potential of exosomes derived from the tumor cells,
which had been genetically modified to express a Mycobacterium tuberculosis
antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor
antigens. RESULTS: We transfected B16 melanoma cells with a plasmid encoding the
M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The
secreted exosomes bearing both tumor-associated antigens and the pathogenic
antigen (or their epitopes) were collected. When the exosomes were injected into
foot pads of mice, they significantly (p < 0.05) evoked cellular immunity against
both ESAT-6, and B16 tumor cells. Intra-tumoral injection of the exosomes
significantly suppressed (p < 0.001) tumor growth in syngeneic B16 tumor-bearing
mice, while the exosomes derived from the non-transfected B16 cells showed no
effect on tumor growth, although both exosomes should have similar tumor
antigens. CONCLUSIONS: Exosomes bearing both tumor antigens and the M.
tuberculosis antigen (or their epitopes) have a high potential as a candidate for
cancer vaccine to overcome the immune escape by tumor cells.
PMID- 27484690
TI - The influence of water resistance therapy on vocal fold vibration: a high-speed
digital imaging study.
AB - PURPOSE: This study investigated the influence of tube phonation into water on
vocal fold vibration. METHOD: Eight participants were analyzed via high-speed
digital imaging while phonating into a silicon tube with the free end submerged
into water. Two test sequences were studied: (1) phonation pre, during, and post
tube submerged 5 cm into water; and (2) phonation into tube submerged 5 cm, 10
cm, and 18 cm into water. Several glottal area parameters were calculated using
phonovibrograms. RESULTS: The results showed individual differences. However,
certain trends were possible to identify based on similar results found for the
majority of participants. Amplitude-to-length ratio, harmonic-to-noise ratio, and
spectral flatness (derived from glottal area) decreased for all tube immersion
depths, while glottal closing quotient increased for 10 cm immersion and contact
quotient for 18 cm immersion. Closed quotient decreased during phonation into the
tube at 5 cm depth, and jitter decreased during and after it. CONCLUSION: Results
suggest that the depth of tube submersion appears to have an effect on phonation.
Shallow immersion seems to promote smoother and more stable phonation, while
deeper immersion may involve increased respiratory and glottal effort to
compensate for the increased supraglottal resistance. This disparity, which is
dependent upon the degree of flow resistance, should be considered when choosing
treatment exercises for patients with various diagnoses, namely hyperfunctional
or hypofunctional dysphonia.
PMID- 27484691
TI - In This Issue: Antiestrogen Withdrawal, Yoga, and a Reflection on Quality of
Clinical Trials.
PMID- 27484693
TI - Modulation of cardiac autonomic tone in non-hypotensive hypovolemia during blood
donation.
AB - Non-hypotensive hypovolemia, observed during mild haemorrhage or blood donation
leads to reflex readjustment of the cardiac autonomic tone. In the present study,
the cardiac autonomic tone was quantified using heart rate and blood pressure
variability during and after non-hypotensive hypovolemia of blood donation. 86
voluntary healthy male blood donors were recruited for the study (age 35 +/- 9
years; weight 78 +/- 12 kg; height 174 +/- 6 cms). Continuous lead II ECG and
beat-to-beat blood pressure was recorded before, during and after blood donation
followed by offline time and frequency domain analysis of HRV and BPV. The
overall heart rate variability (SDNN and total power) did not change during or
after blood donation. However, there was a decrease in indices that represent the
parasympathetic component (pNN50 %, SDSD and HF) while an increase was observed
in sympathetic component (LF) along with an increase in sympathovagal balance
(LF:HF ratio) during blood donation. These changes were sustained for the period
immediately following blood donation. No fall of blood pressure was observed
during the period of study. The blood pressure variability showed an increase in
the SDNN, CoV and RMSSD time domain measures in the post donation period. These
results suggest that mild hypovolemia produced by blood donation is non
hypotensive but is associated with significant changes in the autonomic tone. The
increased blood pressure variability and heart rate changes that are seen only in
the later part of donation period could be because of the progressive hypovolemia
associated parasympathetic withdrawal and sympathetic activation that manifest
during the course of blood donation.
PMID- 27484694
TI - Phytoremediation: State-of-the-art and a key role for the plant microbiome in
future trends and research prospects.
AB - Phytoremediation is increasingly adopted as a more sustainable approach for soil
remediation. However, significant advances in efficiency are still necessary to
attain higher levels of environmental and economic sustainability. Current
interventions do not always give the expected outcomes in field settings due to
an incomplete understanding of the multicomponent biological interactions. New
advances in -omics are gradually implemented for studying microbial communities
of polluted land in situ. This opens new perspectives for the discovery of
biodegradative strains and provides us new ways of interfering with microbial
communities to enhance bioremediation rates. This review presents retrospectives
and future perspectives for plant microbiome studies relevant to
phytoremediation, as well as some knowledge gaps in this promising research
field. The implementation of phytoremediation in soil clean-up management systems
is discussed, and an overview of the promoting factors that determine the growth
of the phytoremediation market is given. Continuous growth is expected since
elimination of contaminants from the environment is demanded. The evolution of
scientific thought from a reductionist view to a more holistic approach will
boost phytoremediation as an efficient and reliable phytotechnology. It is
anticipated that phytoremediation will prove the most promising for organic
contaminant degradation and bioenergy crop production on marginal land.
PMID- 27484695
TI - Targeted tissue perfusion versus macrocirculation-guided standard care in
patients with septic shock (TARTARE-2S): study protocol and statistical analysis
plan for a randomized controlled trial.
AB - BACKGROUND: Septic shock has a 90-day mortality risk of up to 50 %. The
hemodynamic targets, including mean arterial pressure (MAP) are not based on
robust clinical data. Both severe hypotension and high doses of vasopressors may
be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is
relevant. METHODS/DESIGN: The targeted tissue perfusion versus macrocirculation
guided standard care in patients with septic shock (TARTARE-2S) trial is a
prospective, two-parallel-group, randomized, open-label, multicenter trial with
assessor-blinded outcome evaluation. We will randomize at least 200 patients with
septic shock in four European intensive care units (ICUs) to test whether a
tissue perfusion-guided treatment strategy based on capillary refill time,
peripheral temperature, arterial lactate concentrations, and accepting lower MAP
levels, leads to a faster resolution of shock than macrocirculation target-guided
standard care. The primary outcome measure is days alive in 30 days with normal
arterial blood lactate (first value of <2 mmol/L) and without any inotropic or
vasopressor agent. Secondary outcomes include individual components of the
primary outcome, days alive without renal replacement, days alive without
mechanical ventilation in 30 days, and new acute kidney injury. The sample size
enables detection of a 13.5-h difference in the primary outcome with a type 1
error of 5 % and power of 80 %, assuming 25 % mortality and a mean of 650 h (SD
30) among the 30-day survivors. After 150 included patients the statistician
masked for allocation group will recalculate the sample size potentially
increasing the sample up to 300. The Data Safety and Monitoring Board (DSMB) will
review the safety data after 100 patients. DISCUSSION: The TARTARE-2S trial will
provide important clinical data on treatment targets in septic shock, evaluating
the impact of clinical tissue perfusion-guided hemodynamic treatment on a
surrogate outcome combining resolution of shock (hyperlactatemia and
vasopressors/inotropes), and 30-day mortality. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT02579525 . Registered on 19 October 2015.
PMID- 27484696
TI - Preventive effects of Resveratrol against azoxymethane-induced testis injury in
rats.
AB - To evaluate the protective effects of Resveratrol (RES) on azoxymethane (AOM)
induced testicular damage using histopathology and biochemical analyses, 28 male
rats were randomly divided into four groups. Groups were control, RES, AOM and
ARES. At the end of the 7 weeks, following routine tissue processing procedure,
testis sections were stained with haematoxylin-eosin and Masson's trichrome. The
blood samples were taken for biochemical analysis of testosterone, total
oxidative stress, total antioxidant status and oxidative stress index.
Degenerative changes in the seminiferous tubules such as atrophy, loss in the
number of germ cells and arrested spermatogenic cell, and increase in the
connective tissue of the tunica albuginea in the groups with AOM treatment were
found. RES treatment (ARES) reduced the number of affected seminiferous tubules
significantly (p < .05) compared to AOM alone. The testosterone levels in AOM
group were significantly lower than in the control group (p < .05). The total
oxidative stress levels were significantly higher in AOM group compared to
control group (p < .05). The total antioxidant status levels in ARES group were
significantly higher than in the AOM group (p < .05). This study results suggest
that an antioxidant like Resveratrol may be useful for decreasing the harmful
effects of azoxymethane.
PMID- 27484697
TI - Cognitive fusion and emotion differentiation: does getting entangled with our
thoughts dysregulate the generation, experience and regulation of emotion?
AB - We tested whether cognitive fusion impairs emotion differentiation and thereby
mediates relations between cognitive fusion and depression and panic symptoms
among 55 adults (Mage = 26.8 (3.9), 50.9% women). Using visual stimuli, we
elicited multiple emotion states and measured (a) emotional intensity - the
subjective emotion intensity of elicited emotions (i.e. Specific Emotion
Intensity - SEI), as well as (b) emotional differentiation - the degree of co
activation of multiple negative emotions when a specific emotion was elicited
(i.e. Multiple Emotion Co-Activation - MECA). First, as hypothesised, we found
that cognitive fusion predicted lower levels of emotion differentiation (MECA).
In contrast, as hypothesised, these effects were significantly greater than the
(null) effects of cognitive fusion on emotion intensity (SEI). Second, as
predicted, MECA, but not SEI, predicted depression and panic symptoms. Finally,
we found that MECA mediated the effects of cognitive fusion on depression and
panic symptoms. The present findings contribute novel, preliminary empirical
insight into associations between cognitive fusion, impaired emotion
differentiation and mental ill-health.
PMID- 27484692
TI - Are Alcohol Anti-relapsing and Alcohol Withdrawal Drugs Useful in Cannabinoid
Users?
AB - Cannabinoids are still classified as illegal psychoactive drugs despite their
broad and increasingly acknowledged therapeutic potential. These substances are
most famous for their wide recreational use, particularly among young adults to
either alter the state of consciousness, intensify pleasure induced by other
psychoactive substances or as an alternative to the previously abused drugs. It
is important to emphasize that cannabinoids are often taken together with a
variety of medications intended for the treatment of alcohol use disorder (AUD)
or alcohol withdrawal syndrome (AWS). These medications include disulfiram,
acamprosate, and naltrexone. In this paper, we summarize recent advances in the
knowledge of possible beneficial effects and interactions between cannabinoids
and drugs commonly used for treatment of AUD and AWS either comorbid or existing
as a separate disorder.
PMID- 27484698
TI - Effect of stress and attention on startle response and prepulse inhibition.
AB - The startle reflex magnitude can be modulated when a weak stimulus is presented
before the onset of the startle stimulus, a phenomenon termed prepulse inhibition
(PPI). Previous research has demonstrated that emotional processes can modulate
PPI and startle intensity, but the available evidence is inconclusive. In order
to obtain additional evidence in this domain, we conducted two experiments
intended to analyze the effect of induced stress and attentional load on PPI and
startle magnitude. Specifically, in Experiment 1 we used a between subject
strategy to evaluate the effect on startle response and PPI magnitude of
performing a difficult task intended to induce stress in the participants, as
compared to a group exposed to a control task. In Experiment 2 we evaluated the
effect of diverting attention from the acoustic stimulus on startle and PPI
intensity. The results seem to indicate that induced stress can reduce PPI, and
that startle reflex intensity is reduced when attention is directed away from the
auditory stimulus that induces the reflex.
PMID- 27484699
TI - Melatonin modulates tonic immobility and vigilance behavioural responses of
broiler chickens to lighting regimens during the hot-dry season.
AB - Experiments were conducted with the aim of determining the influence of melatonin
administration on vigilance and tonic immobility (TI) responses of Marshall
broiler chickens. The broiler chickens were reared on different lighting regimens
and subjected to heat stress during the hot-dry season. Simple random sampling
was used to assign 300 broiler chicks into three groups, comprising 100 broiler
chicks each. Group I (12D:12L cycle) was raised under natural photoperiod of 12-h
light and 12-h darkness, without melatonin supplementation. Group II (CL) was
kept under 24-h continuous lighting, without melatonin administration. Group III
(CL+MEL) was raised under 24-h continuous lighting; with melatonin
supplementation at 0.5mg/kg per os, via drinking water using a syringe. Beginning
from day-old, broiler chickens in group III were individually administered with
melatonin once daily for 8weeks at 17:00h. TI was induced by manual restraint,
and vigilance elicited at self-righting graded for three days, two weeks apart,
in 15 labeled broiler chickens from each of the three groups; at 06:00h, 13:00h
and 18:00h, starting from week 4-8. Each broiler chicken was laid on its back in
a U-shaped cradle, covered with cloth. Thermal microenvironment parameters of dry
bulb temperature (DBT) and relative humidity (RH) were recorded at the
experimental site, concurrently during the vigilance and TI tests. Inside the
broiler chickens' house, the weekly temperature-humidity index (THI) was lowest
at week 4 of the study, with the value of 48.60+/-0.08 degrees C. At week 4, the
relationship between the THI and TI induction attempts was stronger in 12D:12L
cycle (r=0.589, P<0.001) than CL (r=0.264, P>0.05) or CL+MEL (r=0.096, P>0.05)
broiler chickens. This indicated that the broiler chickens on 12D:12L cycle were
more active compared to their melatonin-treated counterparts, apparently due to
adverse effects of high DBT and high RH on the broiler chickens during the hot
dry season. The highest numbers of TI induction trial attempts were recorded at
13:00h in 12D:12L cycle and CL groups (2.13+/-0.34 and 2.15+/-0.22,
respectively), when the broiler chickens were at week 8. The overall mean values
of induction trial attempts differed significantly (P<0.0001) between the groups;
with the lowest mean values of 1.22+/-0.4 recorded in CL+MEL broiler chickens. At
day 42, the lowest mean TI duration of 101.87+/-10.24s in the CL group, recorded
at 06:00h rose (P<0.001) to 184.07+/-23.69s at 13:00h. The overall mean duration
of TI differed significantly (P<0.0001) again between the groups; with the
highest mean duration of 167.82+/-8.35s, recorded in CL+MEL broiler chickens
administered with melatonin. The overall mean vigilance behavioural ranking
values of 1.85+0.07 and 1.70+0.08, obtained in 12D:12L cycle and CL broiler
chickens, respectively were higher (P<0.0001) than the value of 1.44+0.05
recorded in melatonin-treated broiler chickens. The results indicated that
broiler chickens belonging to both 12D:12L cycle and CL groups were more
emotional, fearful or anxious, compared to CL+MEL broiler chickens. It was
concluded that melatonin administration elicits boldness and confidence by
suppressing freezing behaviour in broiler chickens, and it may improve their
welfare and productivity.
PMID- 27484700
TI - Mapping epigenetic changes to the host cell genome induced by Burkholderia
pseudomallei reveals pathogen-specific and pathogen-generic signatures of
infection.
AB - The potential for epigenetic changes in host cells following microbial infection
has been widely suggested, but few examples have been reported. We assessed
genome-wide patterns of DNA methylation in human macrophage-like U937 cells
following infection with Burkholderia pseudomallei, an intracellular bacterial
pathogen and the causative agent of human melioidosis. Our analyses revealed
significant changes in host cell DNA methylation, at multiple CpG sites in the
host cell genome, following infection. Infection induced differentially
methylated probes (iDMPs) showing the greatest changes in DNA methylation were
found to be in the vicinity of genes involved in inflammatory responses,
intracellular signalling, apoptosis and pathogen-induced signalling. A comparison
of our data with reported methylome changes in cells infected with M.
tuberculosis revealed commonality of differentially methylated genes, including
genes involved in T cell responses (BCL11B, FOXO1, KIF13B, PAWR, SOX4, SYK),
actin cytoskeleton organisation (ACTR3, CDC42BPA, DTNBP1, FERMT2, PRKCZ, RAC1),
and cytokine production (FOXP1, IRF8, MR1). Overall our findings show that
pathogenic-specific and pathogen-common changes in the methylome occur following
infection.
PMID- 27484701
TI - Effects of Dexmedetomidine on motor- and somatosensory-evoked potentials in
patients with thoracic spinal cord tumor: a randomized controlled trial.
AB - BACKGROUND: We hypothesized that the addition of dexmedetomidine in a clinically
relevant dose to propofol-remifentanil anesthesia regimen does not exert an
adverse effect on motor-evoked potentials (MEP) and somatosensory-evoked
potentials (SSEP) in adult patients undergoing thoracic spinal cord tumor
resection. METHODS: Seventy-one adult patients were randomized into three groups.
Propofol group (n = 25): propofol-remifentanil regimenand the dosage was adjusted
to maintain the bispectral index (BIS) between 40 and 50. DP adjusted group (n =
23): Dexmedetomidine (0.5 MUg/kg loading dose infused over 10 min followed by a
constant infusion of 0.5 MUg/kg/h) was added to the propofol-remifentanil regimen
and propofol was adjusted to maintain BIS between 40 and 50. DP unadjusted group
(n = 23): Dexmedetomidine (administer as DP adjusted group) was added to the
propofol-remifentanil regimen and propofol was not adjusted. All patients
received MEP, SSEP and BIS monitoring. RESULTS: There were no significant changes
in the amplitude and latency of MEP and SSEP among different groups (P > 0.05).
The estimated propofol plasma concentration in DP adjusted group (2.7 +/- 0.3
MUg/ml) was significantly lower than in propofol group (3.1 +/- 0.2 MUg/ml) and
DP unadjusted group (3.1 +/- 0.2 MUg/ml) (P = 0.000). BIS in DP unadjusted group
(35 +/- 5) was significantly lower than in propofol group (44 +/- 3) (P = 0.000).
CONCLUSIONS: The addition of dexmedetomidine to propofol-remifentanil regimen
does not exert an adverse effect on MEP and SSEP monitoring in adult patients
undergoing thoracic spinal cord tumor resection. TRIAL REGISTRATION: The study
was registered with the Chinese Clinical Trial Registry on January 31st, 2014.
The reference number was ChiCTR-TRC-14004229.
PMID- 27484702
TI - Chronic Smoking, Trait Anxiety, and the Physiological Response to Stress.
AB - BACKGROUND AND OBJECTIVES: Both chronic smoking and trait anxiety have been
associated with dysregulations in psychobiological stress response systems.
However, these factors have not been studied in conjunction. We expected trait
anxiety and smoking status to attenuate stress reactivity. Furthermore, we
expected an allostatic load effect resulting in particularly attenuated stress
reactivity in high-anxious smokers. In addition, high-anxious smokers were
expected to exhibit increased urges to smoke in response to stress. METHODS: 115
smokers and 37 nonsmokers, aged 18-64 years, completed a laboratory session
including mental stressors such as evaluated public speaking and mental
arithmetic. Trait anxiety was assessed using Spielberger's State-Trait Anxiety
Inventory. Cardiovascular autonomic indices, salivary cortisol, and the desire to
smoke were measured at baseline, during stressors, and at recovery. RESULTS:
Regression analyses showed that smokers exhibited attenuated cardiovascular
stress responses in comparison to nonsmokers. Higher trait anxiety predicted
attenuated systolic blood pressure responses to stress. No interaction effect of
smoking status and trait anxiety was found in stress response measures. Higher
trait anxiety predicted an increased desire to smoke in response to stress among
smokers. CONCLUSION: Results indicate that both smoking status and trait anxiety
are associated with blunted sympatho-adrenal cardiovascular stress reactivity.
Elevated urges to smoke in response to stress found among smokers with high trait
anxiety suggest an important role of anxiety in smoking propensity and relapse.
PMID- 27484704
TI - Blunt traumatic rupture of the right ventricle: visualization of spurting blood
using transthoracic echocardiography.
PMID- 27484703
TI - Delayed gadolinium-enhanced MRI of cartilage and T2 mapping for evaluation of
reparative cartilage-like tissue after autologous chondrocyte implantation
associated with Atelocollagen-based scaffold in the knee.
AB - OBJECTIVE: To elucidate the quality of tissue-engineered cartilage after an
autologous chondrocyte implantation (ACI) technique with Atelocollagen gel as a
scaffold in the knee in the short- to midterm postoperatively, we assessed
delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage
(dGEMRIC) and T2 mapping and clarified the relationship between T1 and T2 values
and clinical results. MATERIALS AND METHODS: In this cross-sectional study, T1
and T2 mapping were performed on 11 knees of 8 patients (mean age at ACI, 37.2
years) with a 3.0-T MRI scanner. T1implant and T2implant values were compared
with those of the control cartilage region (T1control and T2control). Lysholm
scores were also assessed for clinical evaluation. The relationships between the
T1 and T2 values and the clinical Lysholm score were also assessed. RESULTS:
There were no significant differences in the T1 values between the T1implant
(386.64 +/- 101.78 ms) and T1control (375.82 +/- 62.89 ms) at the final follow
up. The implants showed significantly longer T2 values compared to the control
cartilage (53.83 +/- 13.89 vs. 38.21 +/- 4.43 ms). The postoperative Lysholm
scores were significantly higher than the preoperative scores. A significant
correlation was observed between T1implant and clinical outcomes, but not between
T2implant and clinical outcomes. CONCLUSION: Third-generation ACI implants might
have obtained an almost equivalent glycosaminoglycan concentration compared to
the normal cartilage, but they had lower collagen density at least 3 years after
transplantation. The T1implant value, but not the T2 value, might be a predictor
of clinical outcome after ACI.
PMID- 27484705
TI - Rapid reconstitution of CD4 T cells and NK cells protects against CMV
reactivation after allogeneic stem cell transplantation.
AB - BACKGROUND: Epstein-Barr virus and Cytomegalovirus reactivations frequently occur
after allogeneic stem cell transplantation (SCT). METHODS: Here we investigated
the role of immune cell reconstitution in the onset and subsequent severity of
EBV- and CMV-reactivation. To this end, 116 patients were prospectively sampled
for absolute T cell (CD4 and CD8), B-cell (CD19) and NK-cell (CD16 and CD56)
numbers weekly post-SCT during the first 3 months and thereafter monthly until 6
months post-SCT. Viral load was monitored in parallel. RESULTS: In contrast to
the general belief, we found that early T-cell reconstitution does not play a
role in the onset of viral reactivation. CMV reactivation in the first 7 weeks
after SCT however resulted in higher absolute CD8(+) T-cell numbers 6 months post
SCT in patients with high-level reactivation, many of which were CMV-specific.
Interestingly, rapid reconstitution of CD4(+) T-cells, as well as NK cells and
the presence of donor KIR3DL1, are associated with the absence of CMV
reactivation after SCT, suggestive of a protective role of these cells. In
contrast, EBV-reactivations were not affected in any way by the level of immune
reconstitution after SCT. CONCLUSION: In conclusion, these data suggest that
CD4(+) T-cells and NK cells, rather than CD8(+) T-cells, are associated with
protection against CMV-reactivation.
PMID- 27484707
TI - Preparation of a compressible and hierarchically porous polyimide sponge via the
sol-gel process of an aliphatic tetracarboxylic dianhydride and an aromatic
triamine.
AB - A compressible and monolithic microporous polyimide sponge was prepared from an
aliphatic tetracarboxylic dianhydride and an aromatic triamine. The sponge had a
hierarchical pore structure, in which spherical microporous polyimide particles
were interconnected to form a macroscopic network. It showed an amphiphilic
character, because of the balanced presence of hydrophobic and hydrophilic
groups.
PMID- 27484706
TI - Active CMV and EBV infections in renal transplant recipients with unexplained
fever and elevated serum creatinine.
AB - Proper identification of active cytomegalovirus (CMV) and Epstein-Barr virus
(EBV) infections are helpful for monitoring antiviral treatment in transplant
recipients. Qualitative and quantitative CMV, EBV DNA PCR techniques in the
context of serological tests are performed for early detection and
differentiation of active and latent CMV and EBV infections in renal
transplantation. Basically, 129 renal transplanted recipients monitored carefully
and hospitalized for unexplained elevated creatinine levels or high fever and 21
of their donors were studied. CMV DNA was detected in 63.5% of the febrile
episodes following transplantation and in 46.42% of readmitted patients using
qualitative PCR method. In the first group, 15% of the patients and in the second
group 42.85% of the patients had copy numbers more than cutoff point (900
copies/mL). Cutoff point had 100% sensitivity and 82.5% specificity for active
and symptomatic CMV infection. Only 15.5% of the subjects were positive for EBV
infection by qualitative PCR method. Among them 5% had >2000 copies/mL and were
symptomatic. One subject with a history of three times hospitalization had higher
EBV viral load and developed post-transplant lymphoproliferative disorder. CMV
load was significantly correlated with elevated creatinine levels (OR = 3.1, p =
0.006), abnormal heart sounds (OR = 4.7; p = 0.02) and hypertension (OR = 3.6; p
= 0.03). Only qRT-PCR could differentiate between latent and active infections
and might be clinically useful for monitoring symptomatic CMV and EBV infections
and initiation of the antiviral therapy. Elevated creatinine levels,
hypertension, and abnormal heart sounds could be considered as main
manifestations of HCMV infection in kidney recipients.
PMID- 27484709
TI - bFGF Promotes Migration and Induces Cancer-Associated Fibroblast Differentiation
of Mouse Bone Mesenchymal Stem Cells to Promote Tumor Growth.
AB - Tumors recruit bone mesenchymal stem cells (BMSCs) to localize to tumor sites,
which induces their conversion into cancer-associated fibroblasts (CAFs) that
facilitate tumor progression. However, this process is poorly understood on the
molecular level. In this study, we found that 4T1 breast cancer cells promoted
the migration of BMSCs, and bFGF neutralizing antibody inhibited the migration of
BMSCs induced by a tumor-conditioned medium. In addition, exogenous bFGF enhanced
the migration of BMSCs in a dose-dependent manner in vitro. Furthermore, BMSCs
promoted the proliferation of 4T1 tumor cells under BMSC-conditioned medium and
in tumor xenograft model. Dramatically, BMSCs expressed CAF markers and produced
collagen in the tumor microenvironment, and this transition was blocked by bFGF
antibody. In addition, exogenous bFGF induced CAF differentiation of BMSCs. And
bFGF increased phosphorylation of Erk1/2 and Smad3 in BMSCs and Erk inhibitor
PD98059 was shown to block bFGF-induced Erk and Smad3 phosphorylation, suggesting
that Erk/Smad3 signaling pathway involved in BMSC transdifferentiation induced by
bFGF. Collectively, our results indicate that bFGF signaling plays indispensable
roles in BMSC recruitment and transdifferentiation into CAFs and the consequent
protumor effects, and targeting tumor stroma through bFGF inhibition maybe a
promising strategy to suppress tumor progression.
PMID- 27484708
TI - The African-specific S47 polymorphism of p53 alters chemosensitivity.
AB - The TP53 protein is known to affect the sensitivity of tumor cells to cell death
by DNA damaging agents. We recently reported that human and mouse cells
containing an African-specific coding region variant of p53, Pro47Ser (hereafter
S47), are impaired in the transactivation of a small subset of p53 target genes
including GLS2 and SCO2, and are markedly resistant to cisplatin. Further, mice
containing this variant are markedly predisposed to cancer. Together these
findings suggested that cancer-affected humans with the S47 variant might not be
effectively treated with cisplatin. To more directly test this premise, we
created transformed derivatives of mouse embryo fibroblasts (MEFs) containing
wild type p53 (WT) and the S47 variant and analyzed them for chemosensitivity. We
find that transformation with E1A and Ras actually reverses the
chemosensitivity/transcriptional differences between WT p53 and S47.
Specifically, E1A/Ras-transformed S47 cells show increased sensitivity to
cisplatin and paclitaxel, and comparable transactivation of GLS2 and SCO2,
compared to cells with WT p53. These data suggest that the functional differences
between WT p53 and S47 in primary cells may not hold true for transformed cells.
They also offer hope that cisplatin and paclitaxel may be effective
chemotherapeutic drugs for S47 individuals with cancer.
PMID- 27484710
TI - Effect of multipurpose solutions on in vivo surface wettability of a silicone
hydrogel lens.
AB - PURPOSE: To compare the in vivo surface wettability of silicone hydrogel (SiHy)
contact lenses pre-soaked overnight in different multipurpose solutions (MPS) and
normal saline. METHODS: In this double-blinded, randomized and self-controlled
study, 36 subjects were fitted with three pairs of contact lenses (senofilcon A)
pre-soaked overnight in five different MPS and saline in a randomized order. Each
pair of lenses (pre-soaked in two different solutions the night before) were worn
for 15min before assessment of pre-lens non-invasive tear break-up time (PL
NITBUT) using the Medmont corneal topographer (video recording). Corneal
integrity was assessed using a slit lamp and a resting interval of 20min was
allowed between each pair of lenses to ensure post-lens wear corneal integrity.
RESULTS: Thirty subjects completed the study. The median PL-NITBUT ranged from
2.84s to 3.08s with lenses pre-soaked in different MPS, compared to 2.78s with
lenses pre-soaked in saline. No significant differences in PL-NITBUT were found
among lenses pre-soaked in different solutions (p=0.647). CONCLUSION: In vivo
surface wettability, in terms of PL-NITBUT after 15min of lens wear, of
senofilcon A contact lenses pre-soaked overnight in different MPS were not
significantly different from those pre-soaked in saline.
PMID- 27484711
TI - Influenza A Virus in Backyard Pigs and Poultry in Rural Cambodia.
AB - Surveillance of influenza virus in humans and livestock is critical, given the
worldwide public health threats and livestock production losses. Livestock
farming involving close proximity between humans, pigs and poultry is often
practised by smallholders in low-income countries and is considered an important
driver of influenza virus evolution. This study determined the prevalence and
genetic characteristics of influenza A virus (IAV) in backyard pigs and poultry
in Cambodia. A total of 751 animals were tested by matrix gene-based rRT-PCR, and
influenza virus was detected in 1.5% of sampled pigs, 1.4% of chickens and 1.0%
of ducks, but not in pigeons. Full-length genome sequencing confirmed triple
reassortant H3N2 in all IAV-positive pigs and various low pathogenic avian
influenza subtypes in poultry. Phylogenetic analysis of the swine influenza
viruses revealed that these had haemagglutinin and neuraminidase genes
originating from human H3N2 viruses previously isolated in South-East Asia.
Phylogenetic analysis also revealed that several of the avian influenza subtypes
detected were closely related to internal viral genes from highly pathogenic H5N1
and H9N2 formerly sequenced in the region. High sequence homology was likewise
found with influenza A viruses circulating in pigs, poultry and wild birds in
China and Vietnam, suggesting transboundary introduction and cocirculation of the
various influenza subtypes. In conclusion, highly pathogenic subtypes of
influenza virus seem rare in backyard poultry, but virus reassortment, involving
potentially zoonotic and pandemic subtypes, appears to occur frequently in
smallholder pigs and poultry. Increased targeted surveillance and monitoring of
influenza circulation on smallholdings would further improve understanding of the
transmission dynamics and evolution of influenza viruses in humans, pigs and
poultry in the Mekong subregion and could contribute to limit the influenza
burden.
PMID- 27484712
TI - Forecast models for suicide: Time-series analysis with data from Italy.
AB - The prediction of suicidal behavior is a complex task. To fine-tune targeted
preventative interventions, predictive analytics (i.e. forecasting future risk of
suicide) is more important than exploratory data analysis (pattern recognition,
e.g. detection of seasonality in suicide time series). This study sets out to
investigate the accuracy of forecasting models of suicide for men and women. A
total of 101 499 male suicides and of 39 681 female suicides - occurred in Italy
from 1969 to 2003 - were investigated. In order to apply the forecasting model
and test its accuracy, the time series were split into a training set (1969 to
1996; 336 months) and a test set (1997 to 2003; 84 months). The main outcome was
the accuracy of forecasting models on the monthly number of suicides. These
measures of accuracy were used: mean absolute error; root mean squared error;
mean absolute percentage error; mean absolute scaled error. In both male and
female suicides a change in the trend pattern was observed, with an increase from
1969 onwards to reach a maximum around 1990 and decrease thereafter. The
variances attributable to the seasonal and trend components were, respectively,
24% and 64% in male suicides, and 28% and 41% in female ones. Both annual and
seasonal historical trends of monthly data contributed to forecast future trends
of suicide with a margin of error around 10%. The finding is clearer in male than
in female time series of suicide. The main conclusion of the study is that models
taking seasonality into account seem to be able to derive information on
deviation from the mean when this occurs as a zenith, but they fail to reproduce
it when it occurs as a nadir. Preventative efforts should concentrate on the
factors that influence the occurrence of increases above the main trend in both
seasonal and cyclic patterns of suicides.
PMID- 27484713
TI - Neural speech recognition: continuous phoneme decoding using spatiotemporal
representations of human cortical activity.
AB - OBJECTIVE: The superior temporal gyrus (STG) and neighboring brain regions play a
key role in human language processing. Previous studies have attempted to
reconstruct speech information from brain activity in the STG, but few of them
incorporate the probabilistic framework and engineering methodology used in
modern speech recognition systems. In this work, we describe the initial efforts
toward the design of a neural speech recognition (NSR) system that performs
continuous phoneme recognition on English stimuli with arbitrary vocabulary sizes
using the high gamma band power of local field potentials in the STG and
neighboring cortical areas obtained via electrocorticography. APPROACH: The
system implements a Viterbi decoder that incorporates phoneme likelihood
estimates from a linear discriminant analysis model and transition probabilities
from an n-gram phonemic language model. Grid searches were used in an attempt to
determine optimal parameterizations of the feature vectors and Viterbi decoder.
MAIN RESULTS: The performance of the system was significantly improved by using
spatiotemporal representations of the neural activity (as opposed to purely
spatial representations) and by including language modeling and Viterbi decoding
in the NSR system. SIGNIFICANCE: These results emphasize the importance of
modeling the temporal dynamics of neural responses when analyzing their
variations with respect to varying stimuli and demonstrate that speech
recognition techniques can be successfully leveraged when decoding speech from
neural signals. Guided by the results detailed in this work, further development
of the NSR system could have applications in the fields of automatic speech
recognition and neural prosthetics.
PMID- 27484714
TI - Optimal configurations for bipolar radiofrequency ablation that allow deeper
lesion formation: Good catheter-tip cooling, good catheter-tissue contact, and
the next approach.
PMID- 27484715
TI - Prevalence and mechanism of rotor activation identified during atrial
fibrillation by noncontact mapping: Lack of evidence for a role in the
maintenance of atrial fibrillation.
AB - BACKGROUND: It remains unclear whether atrial fibrillation (AF) is maintained by
the rotor. OBJECTIVE: We evaluated the role of the rotor and examined its
mechanism. METHODS: Among 75 patients with AF (60 paroxysmal, 15 persistent AF)
who underwent 3-dimensional noncontact left atrial mapping during AF, we examined
the prevalence and location of rotor activation and elucidated its mechanism.
Catheter ablation was performed in a stepwise fashion (linear roof lesion and
complex fractionated atrial electrogram ablation after pulmonary vein [PV)
isolation) until AF termination. RESULTS: Rotor activation was observed in 11
patients (14.7%; 10 paroxysmal and 1 persistent AF) (tachycardia cycle length
160.0 +/- 19.8 ms). Rotors were observed transiently (duration 6128 +/- 9094 ms)
during AF at the roof (n = 5), septum (n = 3), and ostium of the left superior PV
(n = 3). Five rotors circulated in clockwise and 6 in counterclockwise
directions. The length of the block line at the center of the rotor was 15.2 +/-
6.9 mm. The electrograms at the block line showed low-amplitude multiple
deflections (n = 7) or double potentials (n = 4), and the amplitudes during rotor
activation were significantly lower than those during sinus rhythm (0.27 +/- 0.18
mV vs 1.22 +/- 0.92 mV; P < .01). No conduction disturbances were found during
sinus rhythm, suggesting that the central line of block was formed functionally.
AF was terminated by PV isolation alone without additional lesions in patients
with rotors. CONCLUSION: Functionally formed rotor activation was observed during
AF in a limited number of patients. These rotor activations may not be related to
AF maintenance, but rather may reflect a transient organization of random
propagation.
PMID- 27484716
TI - Celastrol inhibits IL-1beta-induced inflammation in orbital fibroblasts through
the suppression of NF-kappaB activity.
AB - Graves' disease is an autoimmune disease of the thyroid gland, which is
characterized by hyperthyroidism, diffuse goiter and Graves' ophthalmopathy (GO).
Although several therapeutic strategies for the treatment of GO have been
developed, the effectiveness and the safety profile of these therapies remain to
be fully elucidated. Therefore, examination of novel GO therapies remains an
urgent requirement. Celastrol, a triterpenoid isolated from traditional Chinese
medicine, is a promising drug for the treatment of various inflammatory and
autoimmune diseases. CCK-8 and apoptosis assays were performed to investigate
cytotoxicity of celastrol and effect on apoptosis on orbital fibroblasts. Reverse
transcription-polymerase chain reaction, western blotting and ELISAs were
performed to examine the effect of celastrol on interleukin (IL)-1beta-induced
inflammation in orbital fibroblasts from patients with GO. The results
demonstrated that celastrol significantly attenuated the expression of IL-6, IL
8, cyclooxygenase (COX)-2 and intercellular adhesion molecule-1 (ICAM-1), and
inhibited IL-1beta-induced increases in the expression of IL-6, IL-8, ICAM-1 and
COX-2. The levels of prostaglandin E2 in orbital fibroblasts induced by IL-1beta
were also suppressed by celastrol. Further investigation revealed that celastrol
suppressed the IL-1beta-induced inflammatory responses in orbital fibroblasts
through inhibiting the activation of nuclear factor (NF)-kappaB. Taken together,
these results suggested that celastrol attenuated the IL-1beta-induced pro
inflammatory pathway in orbital fibroblasts from patients with GO, which was
associated with the suppression of NF-kappaB activation.
PMID- 27484717
TI - Aluminum alkoxide, amide and halide complexes supported by a bulky dipyrromethene
ligand: synthesis, characterization, and preliminary epsilon-caprolactone
polymerization activity.
AB - Aluminum halide, alkoxide and amide complexes 2-6 of the form (N,N)AlX2-nYn (n =
0, 1 and (N,N) = 1,9-dimesityl-5-phenyldipyrromethene (1)) were synthesized and
characterized by NMR spectroscopy and X-ray crystallography. The in situ
generated lithium salt of dipyrromethene 1 was reacted with AlX3 to afford
aluminum halide complexes (N,N)AlX2 (X = Cl (2), I (3)) which were isolated as
dichroic crystals. Salt metathesis reactions were employed to produce alkoxide
complexes (N,N)Al(Cl)(O(t)Bu) (4) and (N,N)Al(O(t)Bu)2 (5) from compound 2. The
dimethylamide complex (N,N)Al(NMe2)2 (6) was prepared by reaction of
dipyrromethene 1 with [Al(NMe2)3]2. Crystallographic data revealed that the
dipyrromethene is non-planar when bulky coligands are present as in compounds 3
6, while in the dichloride complex 2 the dipyrromethene is planar. Halide
complexes 2 and 3 reacted with adventitious moisture in toluene to afford
crystalline acid-base adducts (N,N)H.HX, (X = Cl (7), I (8)), which adopted
structures reminiscent of anion receptors. Alkoxide and dimethylamide complexes 5
and 6 were also applied as precatalysts for the ring-opening polymerization of
epsilon-caprolactone and preliminary results are reported.
PMID- 27484718
TI - Effects and synergy of feed ingredients on canine neoplastic cell proliferation.
AB - BACKGROUND: Adjunctive use of nutraceuticals in human cancer has shown promise,
but little work has been done in canine neoplasia. Previous human research has
shown that polyphenols and carotenoids can target multiple pathways in vitro and
in vivo. These compounds could synergize or antagonize with currently used
chemotherapies, either increasing or decreasing the effectiveness of these drugs.
Considering the routine and well controlled feeding practices of most dogs, the
use of nutraceuticals incorporated into pet food is attractive, pending proof
that the extracts are able to improve remission rates. The aim of this study was
to examine five feed ingredients for antiproliferative effects, as well as the
interaction with toceranib phosphate and doxorubicin hydrochloride, when treating
canine neoplastic cell lines in vitro. RESULTS: Screening using MTT proliferation
assays showed that green tea, turmeric, and rosemary extracts were the most
effective. Turmeric extract (TE) was the most potent and exhibited synergy with a
rosemary extract (RE) at concentrations from 1 to 25 MUg mL(-1). This combination
had an additive or synergistic effect with chemotherapeutic agents at selected
concentrations within each cell line. No significant effects on cell viability
were observed when the combination therapy was used with normal primary cells.
CONCLUSIONS: The use of turmeric and rosemary extracts in combination may be
worthwhile to investigate in the pre-clinical and clinical neoplastic considering
there are no negative effects on traditional chemotherapy treatment. Further
studies into the pharmacokinetics and mechanisms of action of these extracts
should be investigated.
PMID- 27484719
TI - Redox-responsive alginate microsphere containing cystamine.
AB - Redox-responsive microspheres were prepared by solidifying the alginate- and
cystamine-containing water droplets of O/W emulsion using calcium ion. Emulsions
were prepared using alginate/cystamine mixture solution whose the carboxylic
group/the amino group molar ratio was 1:1, 1:2, and 1:3, and whose the total
concentration was kept to 2% (w/v). The microspheres on Scanning electron
microscopy photographs were almost spherical and they were less than 1 MUm in
diameter. According to the energy-dispersive X-ray spectroscopy, the sulfur
content of the microspheres was found to be 6.1, 11.4, and 14.8% (w/w),
respectively, not markedly different from the calculated content. The release
degree of blue dextran loaded in the microspheres was higher as the cystamine
content was higher. Microspheres released almost the same amount of dye
regardless of dithiothreitol (DTT, a reducing agent) concentration when the
cystamine content was relatively low (e.g. 14.5% (w/w)), whereas they released
dye in DTT concentration-dependent manner when the cystamine content was
relatively high (e.g. 27.0 and 35.1% (w/w)). The light scattering intensity of
alginate/cystamine mixture solution was stronger at a larger amount of cystamine,
indicating that cystamine could cross-link alginate chains. The light scattering
intensity decreased with increasing DTT concentration, possibly because of the
breakdown of the disulfide bond of cystamine. The breakdown of the disulfide bond
could account for why the DTT concentration-dependent release of dye loaded in
the microspheres was observed.
PMID- 27484720
TI - KCNE4 and KCNE5: K(+) channel regulation and cardiac arrhythmogenesis.
AB - KCNE proteins are single transmembrane-segment voltage-gated potassium (Kv)
channel ancillary subunits that exhibit a diverse range of physiological
functions. Human KCNE gene mutations are associated with various
pathophysiological states, most notably cardiac arrhythmias. Of the five isoforms
in the human KCNE gene family, KCNE4 and the X-linked KCNE5 are, to date, the
least-studied. Recently, however, interest in these neglected genes has been
stoked by their putative association with debilitating or lethal cardiac
arrhythmias. The sometimes-overlapping functional effects of KCNE4 and KCNE5 vary
depending on both their Kv alpha subunit partner and on other ancillary subunits
within the channel complex, but mostly fall into two contrasting categories -
either inhibition, or fine-tuning of gating kinetics. This review covers current
knowledge regarding the molecular mechanisms of KCNE4 and KCNE5 function, human
disease associations, and findings from very recent studies of cardiovascular
pathophysiology in Kcne4(-/-) mice.
PMID- 27484722
TI - Inherited platelet function disorders. Diagnostic approach and management.
AB - Inherited platelet function disorders (IPFDs) make up a significant proportion of
congenital bleeding diatheses, but they remain poorly understood and often
difficult to diagnose. Therefore, a rational diagnostic approach, based on a
standardized sequence of laboratory tests, with consecutive steps of increasing
level of complexity, plays a crucial role in the diagnosis of most IPFDs. In this
review we discuss a diagnostic approach through platelet phenotyping and
genotyping and we give an overview of the options for the management of bleeding
in these disorders and an account of the few systematic studies on the bleeding
risk associated with invasive procedures and its treatment.
PMID- 27484721
TI - The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading
to alphavbeta5 integrin activation and TRAIL resistance in human lung cancer
cells.
AB - BACKGROUND: Fibronectin is a mechanically sensitive protein which is organized in
the extracellular matrix as a network of interacting fibrils. The lung tumor
stroma is enriched for fibronectin which is thought to contribute to metastasis
and drug resistance. Fibronectin is an elastic, multi-modular protein made up of
individually folded domains, some of which can stretch in response to increased
mechanical tension. Very little is known about the relationship of fibronectin's
unfolded domains to lung cancer resistance to chemotherapy. In the present study,
we evaluated the impact of unfolding the first Type III domain of fibronectin
(FnIII-1c) on TNF-related apoptosis inducing ligand (TRAIL) resistance. METHODS:
NCI-H460 non-small cell lung cancer cells were treated with FnIII-1c then
assessed for TRAIL-induced apoptosis. Subsequent analysis of FnIII-1c-mediated
signaling pathways was also completed. Human non-small cell lung cancer tissue
sections were assessed for the expression of vitronectin by immunohistochemistry.
RESULTS: FnIII-1c inhibited TRAIL-induced activation of caspase 8 and subsequent
apoptosis in NCI-H460 lung cancer cells. FnIII-1c treatment was associated with
the activation of the phosphatidylinositol-3-kinase/alpha serine/threonine kinase
(PI3K/Akt) pathway and the alphavbeta5 integrin receptor for vitronectin, both of
which were required for TRAIL resistance. Immunohistochemical staining of
sections from non-small cell lung cancers showed that vitronectin was localized
around blood vessels and in the tumor-stroma interface. CONCLUSIONS: Unfolding of
Type III domains within the fibronectin matrix may promote TRAIL resistance
through the activation of a PI3K/Akt/alphavbeta5 signaling axis and point to a
novel mechanism by which changes in secondary structure of fibronectin contribute
to cancer cell resistance to apoptosis.
PMID- 27484723
TI - Nickel-Promoted Recognition of Long DNA Sites by Designed Peptide Derivatives.
AB - We describe the synthesis of designed peptidic modules that self-assemble in
specific DNA sequences of 12 base pairs in the presence of Ni(II) salts. The
modules consist of modified fragments of transcription factors that have been
appropriately engineered to include metal-chelating His and bipyridine ligands.
PMID- 27484724
TI - Unraveling the Thermodynamics of the Folding and Interconversion of Human
Telomere G-Quadruplexes.
AB - Why human telomere DNA fragments fold into different G-quadruplex structures with
parallel, hybrid, and antiparallel strand orientations depending on the
temperature and concentration of co-solutes remains poorly understood. Similarly,
the formation of intermediate structures along the folding or interconversion
pathways is not well understood. Herein, we address these questions by
introducing a conceptual framework, based on the global thermodynamic analysis of
DSC and CD spectroscopy data, which led to a detailed description of the
topological phase space (phase diagram) of the stability of the human telomere
fragment 5'-AGGG(TTAGGG)3 -3' (Tel22). This framework clarifies the driving
forces of quadruplex folding and interconversion processes over a wide range of
temperatures and ion (K(+) , Na(+) ) and polyethylene glycol (PEG) concentrations
and demonstrates their linkage to the human telomere DNA structural features.
PMID- 27484725
TI - Co-expression of ING4 and P53 enhances hypopharyngeal cancer chemosensitivity to
cisplatin in vivo.
AB - Hypopharyngeal cancer is a distinct type of malignant head and neck tumor, which
exhibits low sensitivity to anti-cancer drugs. The importance of developing
methods for reducing chemotherapy resistance, and improving and enhancing
prognosis has previously been emphasized and is considered a challenge for
effective clinical treatment of hypopharyngeal cancer. The current study
investigated the effects of co-expression of inhibitor of growth protein 4 (ING4)
and P53, a tumor suppressor gene, on chemosensitivity to cisplatin in human
hypopharyngeal cancer xenografts in vivo, and the potential molecular mechanisms
involved. A tumor model was established by injecting athymic nude mice with FADU
human hypopharyngeal cancer cells. Five days after intratumoral and peritumoral
injections of an empty adenoviral vector (Ad), Ad-ING4-P53, cisplatin, or a
combination of Ad-ING4-P53 and cisplatin (Ad-ING4-P53 + cisplatin) every other
day for 5 days, the mice were euthanized and their tumors, livers, and kidneys
were removed. The tumor weights were used to calculate the inhibition rate, and
the expression levels of ING4 and P53 were detected by reverse transcription
polymerase chain reaction. Additionally, apoptotic cells were detected using
terminal deoxynucleotidyl transferase dUTP nick end labeling, and
immunohistochemistry determined the levels ING4, P53, B-cell lymphoma-2 (Bcl-2)
and Bcl-2 associated X protein (Bax) protein expression. The results demonstrated
increased expression of ING4 and P53 in the Ad-ING4-P53 groups compared with PBS
and Ad groups, indicating successful introduction of the genes into the tumor
cells. Notably, the Ad-ING4-P53 + cisplatin group exhibited a higher inhibition
rate compared with the four other groups. The results of immunohistochemistry
analysis demonstrated that Bax expression was increased and Bcl-2 was decreased
in the Ad-ING4-P53 + cisplatin group. This suggested that the enhanced cisplatin
chemosensitivity with Ad-ING4-P53 gene therapy in hypopharyngeal cancer
xenografts may be associated with apoptosis induction through upregulation of Bax
expression and downregulation of Bcl-2. The results of the present study
indicated that gene therapy combined with cisplatin treatment may be a promising
treatment for human hypopharyngeal cancer.
PMID- 27484726
TI - Functioning in the Real World: Using Storytelling to Improve Validity in the
Assessment of Executive Functions.
AB - Real-world contexts differ in the clarity of expectations for desired responses,
as do assessment procedures, ranging along a continuum from maximal conditions
that provide well-defined expectations to typical conditions that provide ill
defined expectations. Executive functions guide effective social interactions,
but relations between them have not been studied with measures that are matched
in the clarity of response expectations. In predicting teacher-rated social
competence (SC) from kindergarteners' performance on tasks of executive functions
(EFs), we found better model-data fit indexes when both measures were similar in
the clarity of response expectations for the child. The maximal EF measure, the
Developmental Neuropsychological Assessment, presents well-defined response
expectations, and the typical EF measure, 5 scales from the Thematic Apperception
Test (TAT), presents ill-defined response expectations (i.e., Abstraction,
Perceptual Integration, Cognitive-Experiential Integration, and Associative
Thinking). To assess SC under maximal and typical conditions, we used 2 teacher
rated questionnaires, with items, respectively, that emphasize well-defined and
ill-defined expectations: the Behavior Rating Inventory: Behavioral Regulation
Index and the Social Skills Improvement System: Social Competence Scale. Findings
suggest that matching clarity of expectations improves generalization across
measures and highlight the usefulness of the TAT to measure EF.
PMID- 27484728
TI - Long -term results of transradial rotational atherectomy for heavily calcified
coronary artery lesions.
AB - OBJECTIVE: Percutaneous coronary intervention (PCI) for the heavily calcified
coronary lesions remains a challenge, and the periprocedural complication rates
of the transfemoral approach are high. This study was conducted to investigate
the feasibility and long-term results of the transradial approach for rotational
atherectomy (RA) prior to stent implantation via the transradial approach in
patients with heavily calcified coronary artery lesions. METHODS: RA followed by
stent implantation via the transradial approach was performed in 47 patients with
severely calcified coronary artery lesions in this retrospectively case-control
study. The success rate of the procedure and the 3-year follow-up (36+/-7.5
months) results were analyzed. RESULTS: RA with subsequent stent implantation or
balloon angioplasty procedures were successfully performed in all cases. 6F
guiding catheters were used in 45 cases, and 7F catheters were used in 2
patients. Rotablation was performed with a 1.25-mm burr in 29 cases, a 1.25-mm
burr followed by a 1.5-mm burr in 17 patients, and a 1.75-mm burr in 1 patient.
Percutaneous transluminal coronary angioplasty after RA was performed, followed
by stent implantation in all 47 patients. Restenosis was found in 7 cases (7/38)
at 13 months (13+/-3.6) and in 13 cases (13/28) at 36 months (36+/-7.5) after the
procedure; 3 patients died during the 3-year follow-up. The post-procedure
cumulative 3-year event-free survival rate was 78%. CONCLUSION: RA prior to stent
implantation via the transradial approach is feasible and safe, the success rate
is high, and long-term outcome is satisfactory in patients with heavily calcified
lesions of the coronary artery.
PMID- 27484729
TI - Hematological and Histological Changes in Prussian Carp Carassius gibelio
Infected with Cyprinid Herpesvirus 2.
AB - Outbreaks of cyprinid herpesvirus 2 (CyHV-2) disease, also known as herpesviral
hematopoietic necrosis, among cultured Prussian Carp Carassius gibelio has
occurred each year in Jiangsu province, China, since 2009. In autumn 2014,
hematological, blood biochemical, and histological changes in naturally infected
moribund Prussian Carp were investigated after CyHV-2 was confirmed as the sole
etiologic agent by etiological analyses. Total erythrocyte count, total leukocyte
count, hemoglobin concentration, and thrombocyte count were significantly reduced
(P < 0.01), whereas erythrocyte osmotic brittleness was significantly increased
(P < 0.01) in infected fish compared with control fish. In addition, monocyte
count was higher (P < 0.01) and lymphocyte count was lower (P < 0.01) in diseased
fish than in control fish. The blood biochemical analyses indicated significant
increases (P < 0.01) in the activities of alanine aminotransferase, aspartate
aminotransferase, alkaline phosphatase, and lactate dehydrogenase as well as in
the levels of total protein, globulin, total bilirubin, creatinine, and urea
along with significant decreases (P < 0.01) in glucose and albumin in the
diseased group. Histopathological examinations indicated that the kidneys and
spleens of moribund Prussian Carp were the most severely lesioned organs,
followed by the gills and hearts. Hypertrophied nuclei with marginated chromatin
also appeared in the hearts and renal tubular epithelia from diseased fish.
Pathological analysis of blood cells showed that approximately 78% of
erythrocytes and 94% of leukocytes were lesioned with different levels of
degeneration and necrosis in the diseased group. These previously unreported
observations may be useful in the diagnosis of CyHV-2 disease. Received May 11,
2015; accepted March 24, 2016.
PMID- 27484727
TI - Adipose tissue-derived stem cells suppress hypertrophic scar fibrosis via the
p38/MAPK signaling pathway.
AB - BACKGROUND: Hypertrophic scars (HS) generally occur after injury to the deep
layers of the dermis, resulting in functional deficiency for patients. Growing
evidence has been identified that the supernatant of adipose tissue-derived stem
cells (ADSCs) significantly ameliorates fibrosis of different tissues, but
limited attention has been paid to its efficacy on attenuating skin fibrosis. In
this study, we explored the effect and possible mechanism of ADSC-conditioned
medium (ADSC-CM) on HS. METHOD: Real-time quantitative polymerase chain reaction
(qRT-PCR) and Western blotting were used to detect the expression of collagen I
(Col1), collagen III (Col3), and alpha-smooth muscle actin (alpha-SMA) after
fibroblasts and cultured HS tissues were stimulated with ADSC-CM and p38
inhibitor/activator. Immunofluorescence staining was performed to test the
expression of alpha-SMA. Masson's trichrome staining, hematoxylin and eosin (H&E)
staining, and immunohistochemistry staining were carried out to assess the
histological and pathological change of collagen in the BALB/c mouse excisional
model. All data were analyzed by using SPSS17.0 software. Statistical analysis
was performed by Student's t tests. RESULTS: The in vitro and ex vivo study
revealed ADSC-CM decreased the expression of Col1, Col3, and alpha-SMA. Together,
thinner and orderly arranged collagen was manifested in HS tissues cultured with
ADSC-CM. Dramatically, the assessed morphology showed an accelerated healing
rate, less collagen deposition, and col1- and col3-positive cells in the ADSC-CM
treated group. Importantly, the protein level of p-p38 was downregulated in a
concentration-dependent manner in HS-derived fibroblasts with ADSC-CM treatment,
which further decreased the expression of p-p38 after the application of its
inhibitor, SB203580. SB203580 led to an obvious decline in the expression of
Col1, Col3, and alpha-SMA in fibroblasts and cultured HS tissues and presented
more ordered arrangement and thinner collagen fibers in BALB/c mice. Lastly,
anisomycin, an agonist of p38, upregulated the expression of fibrotic proteins
and revealed more disordered structure and denser collagen fibers. CONCLUSION:
This study demonstrated that ADSC-CM could decrease collagen deposition and scar
formation in in vitro, ex vivo and in vivo experiments. The regulation of the
p38/MAPK signaling pathway played an important role in the process. The
application of ADSC-CM may provide a novel therapeutic strategy for HS treatment,
and the anti-scarring effect can be achieved by inhibition of the p38/MAPK
signaling pathway.
PMID- 27484731
TI - Effects of melatonin and gonadal androgens on cell proliferation in the pituitary
of viscachas (Lagostomus maximus maximus).
AB - OBJECTIVES: Melatonin and androgens are involved in the regulation of cell
proliferation. However, effects of these hormones on pituitary pars distalis (PD)
of male viscachas is not fully understood. In the present study, we analysed
melatonin and gonadal androgens' effects on proliferating cell nuclear antigen
(PCNA) expression. MATERIALS AND METHODS: Pituitary glands from foetuses,
immature individuals, prepubertal individuals and adult viscachas during their
reproductive cycle, after melatonin administration and after castration, were
used. PCNA-ir cells were detected by immunocytochemistry and morphometrically
quantified using image analysis. RESULTS: Total percentage of PCNA-ir cells
varied seasonally in the adult pituitary, with maximum values during the
reproductive period and minima during gonadal regression periods. Percentages of
PCNA-ir cells increased after melatonin administration, whereas it decreased
after castration. Caudal end and ventral regions were the PD zones which were
most affected by seasonal variations and castration. PCNA expression was highest
in foetal pituitary from midpregnancy. Numbers of PCNA-ir cells decreased during
sexual maturity. CONCLUSIONS: Our results demonstrate the effect of gonadal
androgens on cell proliferation during the reproductive period and sexual
maturity of these animals. Exogenous melatonin increased PD cell proliferation in
adults. Thus, these hormones seem to be involved in different mechanisms that
regulate cell renewal of PD in this seasonally breeding rodent.
PMID- 27484730
TI - Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in
hepatocellular carcinoma cells.
AB - Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers;
however, traditional chemotherapy often suffers from low efficiency caused by
drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and
arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo
NP) with significant drug synergy and pH-triggered drug release for effective
treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP
exhibits the synergistic effect of DNA damage by DOX along with DNA repair
interference by ATO, which results in unprecedented killing efficiency on DOX
resistant cancer cells. More importantly, we explored the possible mechanism is
that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP,
which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation
suppression and DNA lesions accumulation. This study provides a smart drug
delivery strategy to develop a novel synergistic combination therapy for
effectively overcome drug- resistant cancer cells.
PMID- 27484732
TI - A new sesquiterpene lactone from yacon leaves.
AB - The chemical constituents of 60% EtOH extract of yacon leaves were separated to
yield a new compound, together with four known compounds, which were isolated for
the first time from yacon. The new compound was characterised and named as
chlorodalin (1) on the basis of NMR (1D and 2D), HR-MS and other spectral
methods. The cytotoxic activities of 1-5 were evaluated on two human tumour cell
lines and the new compound showed significant cytotoxic activity.
PMID- 27484733
TI - Melatonin enhances thermotolerance by promoting cellular protein protection in
tomato plants.
AB - Melatonin is a pleiotropic signaling molecule that provides physiological
protection against diverse environmental stresses in plants. Nonetheless, the
mechanisms for melatonin-mediated thermotolerance remain largely unknown. Here,
we report that endogenous melatonin levels increased with a rise in ambient
temperature and that peaked at 40 degrees C. Foliar pretreatment with an optimal
dose of melatonin (10 MUmol/L) or the overexpression of N-acetylserotonin
methyltransferase (ASMT) gene effectively ameliorated heat-induced
photoinhibition and electrolyte leakage in tomato plants. Both exogenous
melatonin treatment and endogenous melatonin manipulation by overexpression of
ASMT decreased the levels of insoluble and ubiquitinated proteins, but enhanced
the expression of heat-shock proteins (HSPs) to refold denatured and unfolded
proteins under heat stress. Meanwhile, melatonin also induced expression of
several ATG genes and formation of autophagosomes to degrade aggregated proteins
under the same stress. Proteomic profile analyses revealed that protein
aggregates for a large number of biological processes accumulated in wild-type
plants. However, exogenous melatonin treatment or overexpression of ASMT reduced
the accumulation of aggregated proteins. Aggregation responsive proteins such as
HSP70 and Rubisco activase were preferentially accumulated and ubiquitinated in
wild-type plants under heat stress, while melatonin mitigated heat stress-induced
accumulation and ubiquitination of aggregated proteins. These results suggest
that melatonin promotes cellular protein protection through induction of HSPs and
autophagy to refold or degrade denatured proteins under heat stress in tomato
plants.
PMID- 27484734
TI - Seropositivity of Varicella zoster virus in vaccinated Korean children and MAV
vaccine group.
AB - In 2005, a single-dose varicella vaccination was incorporated into the national
immunization program in Korea. Although the Oka strain is the most commonly
circulating Varicella zoster virus (VZV) genotype in Korea, a domestically
manufactured vaccine based on the MAV strain is widely distributed in Korea. High
vaccination coverage was achieved, but breakthrough infections were frequently
reported. Therefore, in this study, we aimed to analyze the maintenance of
immunity after single-dose vaccination and to compare the immunity provided by
the MAV and Oka vaccines. Enzyme-linked immunosorbent assays of samples from 715
vaccinated Korean children were used to assess seropositivity rates against VZV.
Additionally, fluorescent-antibody-to-membrane-antigen (FAMA) tests were
performed in 35 individuals in the MAV vaccine group, and seropositivity rates
against the Oka strain were determined. The progressive decrease of the
seropositivity rate was demonstrated from ages 1 to 4 as follows: 65% in age 1,
59% in age 2, 53% in age 3, 49% in age 4. It then increased to 62% in age 5 and
70% in age 6. Both the MAV and Oka vaccine groups showed a progressive decrease
of the seropositivity rate from the age of 1 to 4 years, but the MAV vaccine
group had higher seropositivity rates. In FAMA test, the MAV group demonstrated
71% seropositivity against the Oka strain. This study indicates that immunity
wanes after single-dose varicella vaccination and that the MAV vaccine is not
inferior to the Oka vaccine in providing immunity against VZV. The MAV vaccine
also induced cross-immunity against circulating Oka strain.
PMID- 27484735
TI - Self-Printing on Graphitic Nanosheets with Metal Borohydride Nanodots for
Hydrogen Storage.
AB - Although the synthesis of borohydride nanostructures is sufficiently established
for advancement of hydrogen storage, obtaining ultrasmall (sub-10 nm) metal
borohydride nanocrystals with excellent dispersibility is extremely challenging
because of their high surface energy, exceedingly strong
reducibility/hydrophilicity and complicated composition. Here, we demonstrate a
mechanical-force-driven self-printing process that enables monodispersed (~6 nm)
NaBH4 nanodots to uniformly anchor onto freshly-exfoliated graphitic nanosheets
(GNs). Both mechanical-forces and borohydride interaction with GNs stimulate
NaBH4 clusters intercalation/absorption into the graphite interlayers acting as a
'pen' for writing, which is accomplished by exfoliating GNs with the 'printed'
borohydrides. These nano-NaBH4@GNs exhibit favorable thermodynamics (decrease in
?H of ~45%), rapid kinetics (a greater than six-fold increase) and stable de-/re
hydrogenation that retains a high capacity (up to ~5 wt% for NaBH4) compared with
those of micro-NaBH4. Our results are helpful in the scalable fabrication of zero
dimensional complex hydrides on two-dimensional supports with enhanced hydrogen
storage for potential applications.
PMID- 27484736
TI - Happle-Tinschert syndrome can be caused by a mosaic SMO mutation and is suggested
to be a variant of Curry-Jones syndrome.
PMID- 27484737
TI - The withdrawal of antiepileptic drugs in patients with low-grade and anaplastic
glioma.
AB - INTRODUCTION: The withdrawal of antiepileptic drugs (AEDs) in World Health
Organization (WHO) grade II-III glioma patients with epilepsy is controversial,
as the presence of a symptomatic lesion is often related to an increased risk of
seizure relapse. However, some glioma patients may achieve long-term seizure
freedom after antitumor treatment, raising questions about the necessity to
continue AEDs, particularly when patients experience serious drug side effects.
Areas covered: In this review, we show the evidence in the literature from 1990
2016 for AED withdrawal in glioma patients. We put this issue into the context of
risk factors for developing seizures in glioma, adverse effects of AEDs, seizure
outcome after antitumor treatment, and outcome after AED withdrawal in patients
with non-brain tumor related epilepsy. Expert commentary: There is currently
scarce evidence of the feasibility of AED withdrawal in glioma patients. AED
withdrawal could be considered in patients with grade II-III glioma with a
favorable prognosis, who have achieved stable disease and long-term seizure
freedom. The potential benefits of AED withdrawal need to be carefully weighed
against the presumed risk of seizure recurrence in a shared decision-making
process by both the clinical physician and the patient.
PMID- 27484738
TI - ff14IDPs force field improving the conformation sampling of intrinsically
disordered proteins.
AB - Intrinsically disordered proteins are proteins which lack of specific tertiary
structure and unable to fold spontaneously without the partner binding. These
intrinsically disordered proteins are found to associate with various diseases,
such as diabetes, cancer, and neurodegenerative diseases. However, current widely
used force fields, such as ff99SB, ff14SB, OPLS/AA, and Charmm27, are
insufficient in sampling the conformational characters of intrinsically
disordered proteins. In this study, the CMAP method was used to correct the
phi/psi distributions of disorder-promoting amino acids. The simulation results
show that the force filed parameters (ff14IDPs) can improve the phi/psi
distributions of the disorder-promoting amino acids, with RMSD less than 0.10%
relative to the benchmark data of intrinsically disordered proteins. Further test
suggests that the calculated secondary chemical shifts under ff14IDPs are in
quantitative agreement with the data of NMR experiment for five tested systems.
In addition, the simulation results show that ff14IDPs can still be used to model
structural proteins, such as tested lysozyme and ubiquitin, with better
performance in coil regions than the original general Amber force field ff14SB.
These findings confirm that the newly developed Amber ff14IDPs is a robust model
for improving the conformation sampling of intrinsically disordered proteins.
PMID- 27484739
TI - Diffuse reduction of cerebral grey matter volumes in Erdheim-Chester disease.
AB - BACKGROUND: Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis
characterized by systemic inflammation and granulomatous infiltration of multiple
organs including the central nervous system (CNS), bones, and retroperitoneum.
CNS infiltration occurs in one third of patients, but cognitive changes are
common in patients without CNS disease. Here we investigate whether there is a
neuroanatomic basis to observed cognitive deficits, even in absence of CNS
disease. METHODS: We present a volumetric analysis of eleven ECD patients without
CNS tumors or prior neurotoxic treatments. RESULTS: Compared to age-matched
controls, ECD patients have diffuse, bihemispheric reduction in cortical
thickness and subcortical gray matter. CONCLUSIONS: These findings provide the
first corroborating evidence for neurologic disease in ECD patients without
direct CNS infiltration.
PMID- 27484740
TI - Socioeconomic costs and health-related quality of life in juvenile idiopathic
arthritis: a cost-of-illness study in the United Kingdom.
AB - BACKGROUND: Juvenile idiopathic arthritis (JIA) refers to a number of rare
chronic inflammatory diseases. Although JIA imposes a significant societal
burden, limited data are available on the cost of JIA. The study's objective is
to quantify the socioeconomic burden of JIA patients in the United Kingdom (UK),
along with their health-related quality of life (HRQoL). METHODS: A bottom-up,
cross-sectional, cost-of-illness analysis of 23 patients was carried out. To
collect data on demographic characteristics, health resource utilization,
informal care, productivity losses and HRQoL, questionnaires were administered to
and completed by patients or their caregivers. The EuroQol five dimensions (EQ
5D) instrument was used to measure HRQoL. RESULTS: This study found that the
average annual cost for a JIA patient was ?31,546, with direct health care costs
equalling ?14,509 (46.0 % of total costs), direct non-health care costs amounting
to ?8,323 (26.4 %) and productivity losses being ?8,715 (27.6 %). This was
calculated using unit costs for 2012. The largest expenditures on average were
accounted for by early retirement (27.0 %), followed by informal care (24.1 %),
medications (21.1 %), outpatient and primary health care visits (13.2 %) and
diagnostic tests (7.9 %). Important differences existed between JIA patients in
need of caregiver assistance and those with no need (?39,469 vs. ?25,452
respectively). Among adult JIA patients, mean EQ-5D index scores and visual
analogue scale (VAS) scores were found to be 0.26 and 49.00 respectively; the
same scores among caregivers were 0.66 and 67.14 respectively. CONCLUSION: JIA
poses a significant cost burden on the UK society. Over half of the total average
costs (54 %) are related to non-health care and productivity losses. HRQoL of JIA
patients is considerably worse than the UK general population.
PMID- 27484741
TI - Bioaccumulation of thallium and other trace metals in Biscutella laevigata nearby
a decommissioned zinc-lead mine (Northeastern Italian Alps).
AB - The mineral body exploited in Salafossa (Eastern Dolomites) was one of the
largest lead/zinc-containing mineral deposits in Europe. Both metals were mainly
present as sulphides (sphalerite, ZnS and galena, PbS). Mining activity started
around 1550, but it was only around 1960 that the richest veins of the minerals
were discovered. The mine closed in 1985, and concentrations of several trace
metals, such as thallium (Tl), iron (Fe), manganese (Mn), lead (Pb) and zinc
(Zn), were detected in the soils and plant samples (Biscutella laevigata L.) that
were collected from eighteen sites selected outside the mine. B. laevigata is a
pseudometallophyta species, and it often grows near mining areas where the soil's
metal concentrations are significantly higher than those of soil with a natural
geochemical background. The total metal concentrations in the plant tissue (roots
and leaves of Biscutella laevigata) and in the soil samples - both bulk-soil and
the B. laevigata root system (rhizo-soil) - were determined through Inductively
Coupled Plasma Optical Emission Spectrometry (ICP-OES). The metal extractability
and leachability of the soil samples were estimated using soil extractions with
DTPA (Diethylenetriaminepentaacetic acid). In addition, metal mobility caused by
rainwater runoff was estimated by using a leaching test with a dilute solution of
H2SO4 and HNO3. The results showed that metals were present in a chemical form
available for uptake by the plants' roots. In fact, high concentrations of the
metals were also found in the plant tissue (roots and leaves) of B. laevigata,
and these concentrations were higher than those whose soils present natural
geochemical background levels in the corresponding rhizo-soil. Thus, B. laevigata
has shown a marked ability to bioaccumulate trace metals, especially Tl and, to a
lesser extent, Zn, Pb, Fe and Mn, and it can influence metal mobility in the
rhizo-soil. To assess the uptake and translocation processes of the trace metals,
resulting in their bioaccumulation, two different indices were calculated: the
enrichment factor in roots (EFr), as the ratio between the metal concentration in
belowground biomass and in the respective rhizo-soil, and the translocation
factor (TF), as the ratio between the metal concentration in the leaves and the
corresponding roots. For both indices, values > 1 denoted enrichment of the metal
in the roots or its translocation to the upper tissues. The results showed that
EFr and TF were considerably high only for Tl, reaching a maximum value of 60 for
EFr and 11.6 for TF. Conversely, the other investigated metals did not show
significant bioaccumulation (EFr < 1), and they showed TF > 1 only at a few
sites.
PMID- 27484742
TI - A health fundraising experiment using the "foot-in-the-door" technique.
AB - Foot-in-the-door (FITD) involves obtaining compliance with a small request to
boost compliance with a larger request. Only a few studies to date have tested
the technique in health and fundraising contexts, and even fewer have examined
the psychological processes involved. To address these gaps, we conducted an
experiment as an actual fundraiser for a cancer-awareness organization. The
technique activated a self-concept as a supporter of cancer awareness among those
in the FITD condition. Donation amount was also higher among those in FITD, but
only among those with higher levels of worry and low to moderate levels of
preference for consistency.
PMID- 27484744
TI - Fimbriatols A-J, Highly Oxidized ent-Kaurane Diterpenoids from Traditional
Chinese Plant Flickingeria fimbriata (B1.) Hawkes.
AB - Fimbriatols A-J (1-10), ten new ent-kaurane diterpenoids possessing differently
highly oxidized sites, were isolated from Flickingeria fimbriata (B1.) Hawkes.
The structures of these new compounds were determined by HRESI-MS, NMR, CD
spectra and X-ray diffraction analysis. Compound 1 displayed moderately
inhibitory ratio (48.5%) compared with the positive compound NSC-87877 (81.6%) at
the concentration of 0.022 MUg/mL. Compounds 7-10 possess 3, 4-seco-ent-kaurane
skeleton containing a disaccharide moiety with an unusual linkage at C-2' to C
1'' instead of the common linkage at C-6' to C-1'', and this is the first report
in 600 more ent-kauranes found in nature, which might be originated from ent
kaurane diterpenoids through post-modified reactions of Baeyer-Villiger
oxygenation and glycosylation.
PMID- 27484743
TI - S-Nitrosoglutathione ameliorates acute renal dysfunction in a rat model of
lipopolysaccharide-induced sepsis.
AB - OBJECTIVE: Sepsis induces an inflammatory response that results in acute renal
failure (ARF). The current study is to evaluate the role of S-Nitrosoglutathione
(GSNO) in renoprotection from lipopolysaccharide (LPS)-induced sepsis. METHODS:
Rats were divided to three groups. First group received LPS (5 mg/kg body
weight), second group was treated with LPS + GSNO (50 MUg/kg body weight), and
third group was administered with vehicle (saline). They were sacrificed on day 1
and 3 post-LPS injection. Serum levels of nitric oxide (NO), creatinine and blood
urea nitrogen (BUN) were analysed. Tissue morphology, T lymphocyte infiltrations,
and the expression of inflammatory (TNF-alpha, iNOS) and anti-inflammatory (IL
10) mediators as well as glutathione (GSH) levels were determined. KEY FINDING:
Lipopolysaccharide significantly decreased body weight and increased cellular T
lymphocyte infiltration, caspase-3 and iNOS and decreased PPAR-gamma in renal
tissue. NO, creatinine and BUN were significantly elevated after LPS challenge,
and they significantly decreased after GSNO treatment. TNF-alpha level was found
significantly increased in LPS-treated serum and kidney. GSNO treatment of LPS
challenged rats decreased caspase-3, iNOS, TNF-alpha, T lymphocyte infiltration
and remarkably increased levels of IL-10, PPAR-gamma and GSH. CONCLUSION: GSNO
can be used as a renoprotective agent for the treatment of sepsis-induced acute
kidney injury.
PMID- 27484745
TI - Design and characterization of a polyamine derivative inhibiting the expression
of type III secretion system in Pseudomonas aeruginosa.
AB - The type III secretion system (TTSS) of Pseudomonas aeruginosa is a key virulence
determinant for infection of eukaryotic hosts. Based on the findings that
spermidine-mediated host-pathogen signalling is important for activation of type
III secretion systems (TTSS), in this study, we designed, synthesized and
evaluated a series of polyamine derivatives for their potentials in inhibiting
the expression TTSS in P. aeruginosa. In vitro assay of 15 compounds synthesized
in this study unveiled stringent structural requirements for TTSS-inhibitory
activity. Among them, R101SPM, a conjugate between rhodamine 101 and spermine,
showed a potent activity in inhibition of the TTSS gene expression and in
attenuation of the TTSS-mediated cytotoxicity on human cells. In vivo analysis
demonstrated that R101SPM could rescue mice from the lethal infection by P.
aeruginosa. Moreover, genetic analysis showed that the full TTSS-inhibitory
activity of R101SPM required a functional spermidine transporter. Taken together,
our results present a new class of lead molecules for developing anti-virulence
drugs and demonstrate that the spermidine transporter SpuDEGHF of P. aeruginosa
is a promising drug target.
PMID- 27484746
TI - The Medina Embolic Device: early clinical experience from a single center.
AB - OBJECTIVE: To report our initial experience with the Medina Embolic Device (MED)
in unruptured intracranial aneurysms either as sole treatment or in conjunction
with additional devices. METHODS: 15 consecutive patients (6 women, 9 men) with
unruptured aneurysms were treated between September 2015 and April 2016. The
aneurysm fundus measured at least 5 mm. We evaluated the angiographic appearances
of treated aneurysms at the end of the procedure and at follow-up, the clinical
status, complications, and requirement for adjunctive devices. RESULTS: The MED
was successfully deployed in all but one case and adjunctive devices were
required in 10 cases. Aneurysm locations were middle cerebral artery bifurcation
(n=3), internal carotid artery (ICA) bifurcation (n=1), supraclinoid ICA (n=5),
posterior communicating artery (n=1), anterior communicating artery (n=2),
cavernous ICA (n=2), distal basilar sidewall (n=1), basilar tip (n=1). Three
patients had complications although none could be attributed to the MED.
Immediate angiographic results were modified Raymond-Roy classification (mRRC)
I=1, mRRC II=5, mRRC IIIa=3, mRRC IIIb=5, and one patient showed contrast stasis
within the fundus of the aneurysm. Follow-up angiography was available in 11
patients, with four showing complete aneurysm exclusion, six with stable remnants
and one patient with an enlarging neck remnant. CONCLUSIONS: The MED represents a
major step forward in the treatment of intracranial aneurysms. It can result in
rapid exclusion of an aneurysm from the circulation and has a good safety
profile. We believe that the true value of the MED will be in combining its use
with adjunctive devices such as endoluminal flow diverters that will result in
rapid aneurysmal exclusion.
PMID- 27484747
TI - List-learning and verbal memory profiles in childhood epilepsy syndromes.
AB - Findings of material-specific influences on memory performance in pediatric
epilepsy are inconsistent and merit further investigation. This study compared 90
children (aged 6years to 16years) with childhood absence epilepsy (CAE), frontal
lobe epilepsy (FLE), and temporal lobe epilepsy (TLE) to determine whether they
displayed distinct list-learning and verbal memory profiles on the California
Verbal Learning Test - Children's Version (CVLT-C). Group comparison identified
greater risk of memory impairment in children with TLE and FLE syndromes but not
for those with CAE. While children with TLE performed worst overall on Short
Delay Free Recall, groups with TLE and FLE performed similarly on Long Delay Free
Recall. Contrast indices were then employed to explore these differences.
Children with TLE demonstrated a significantly greater retroactive interference
(RI) effect compared with groups with FLE and CAE. Conversely, children with FLE
demonstrated a significantly worse learning efficiency index (LEI), which
compares verbal memory following repetition with initial recall of the same list,
than both children with TLE and CAE. These findings indicated shallow encoding
related to attentional control for children with FLE and retrieval deficits in
children with TLE. Finally, our combined sample showed significantly higher rates
of extreme contrast indices (i.e., 1.5 SD difference) compared with the CVLT-C
standardization sample. These results underscore the high prevalence of memory
dysfunction in pediatric epilepsy and offer support for distinct patterns of
verbal memory performance based on childhood epilepsy syndrome.
PMID- 27484748
TI - The relationship between white matter abnormalities and cognitive functions in
new-onset juvenile myoclonic epilepsy.
AB - Diffusion tensor imaging (DTI) has revealed evidence of subcortical white matter
abnormalities in the frontal area in juvenile myoclonic epilepsy (JME). Decreased
fractional anisotropy (FA) and increased mean diffusivity (MD) in the
corticothalamic pathway have been detected in adult patients with JME. It has
been demonstrated that, in adult patients with JME, frontal dysfunction is
related to subcortical white matter damage and decreased volume in frontal
cortical gray matter and the thalamus. Many studies have focused on adult
patients. Twenty-four patients and 28 controls were evaluated. The group with JME
had significantly worse results for the word fluency, trail-B, and Stroop tests
that assessed executive functions. A significant decrease in FA values in the
dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the
right thalamus, the posterior cingulate, the corpus callosum anterior, the corona
radiata, and the middle frontal white matter (MFWM) and an increase in ADC values
in patients with JME were detected. The correlation between FA values in DLPFC
and the letter fluency test results was positive, and the correlation with the
Stroop and trail-B test results was negative. We found a negative correlation
between SMA, anterior thalamus, and MFWM FA values and the trail-B test results
and a positive correlation between the SMA, anterior thalamus, and MFWM FA values
and the letter fluency test results. We detected white matter and gray matter
abnormalities in patients with new-onset JME using DTI. In addition, we
determined the relationship between cognitive deficit and microstructural
abnormalities by evaluating the correlation between the neuropsychological test
battery results and DTI parameters. We evaluated newly diagnosed patients with
JME in our study. That leads us to believe that microstructural abnormalities
exist from the very beginning of the disease and that they result from the
genetic basis of the disease.
PMID- 27484749
TI - Management of Juvenile Idiopathic Arthritis: A Clinical Guide.
AB - Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease
of childhood. The outcome in patients with JIA has markedly improved with the
advent of biologic drugs. Although early aggressive therapy with biologics seems
to be very effective, this approach leads to overtreatment in patients who would
respond to classic disease-modifying anti-rheumatic drugs. Therefore,
methotrexate remains first-line long-term therapy for most children with
polyarticular JIA. Tumor necrosis factor-alpha inhibitors have shown tremendous
benefit in children with refractory non-systemic JIA. Similar effects have been
observed with interleukin-1 and interleukin-6 blockade in patients with systemic
JIA. Correct choice and timely use of available medications to achieve early and
sustained remission with as few side effects as possible remain challenges for
the treating physician. In this review, a practical, clinically oriented guide to
the management of JIA is provided, focusing on pharmacological treatment with non
steroidal anti-inflammatory drugs, intra-articular and systemic corticosteroids,
disease-modifying anti-rheumatic drugs, and biologic agents. In addition, issues
regarding treatment failure, early aggressive treatment, and drug tapering are
discussed, with alternative treatment options being suggested.
PMID- 27484750
TI - Alcohol consumption among partners of pregnant women in Sweden: a cross sectional
study.
AB - BACKGROUND: Antenatal care in Sweden involves a visit in pregnancy week 6-7 for
counseling about lifestyle issues, including alcohol. The aim of this study was
to investigate alcohol consumption among partners of pregnant women, their
motives for changing drinking patterns when becoming a parent and their
perceptions of the midwife's counseling about alcohol. METHOD: The study was
conducted at 30 antenatal care centers across Sweden in 2009-2010. All partners
who accompanied a pregnant women in pregnancy week >17 were asked to participate.
The questionnaire included questions on alcohol consumption. RESULTS:
Questionnaires from 444 partners were analyzed. Most, 95 %, of the partners
reported alcohol consumption before pregnancy; 18 % were binge drinking (6
standard drinks or more per occasion, each drink containing 12 grams of pure
alcohol) at least once every month during the last year. More than half, 58 %, of
all partners had decreased their alcohol consumption following pregnancy
recognition and a higher proportion of binge drinkers decreased their consumption
compared to non-frequent binge drinkers (p = 0.025). Their motives varied; the
pregnancy itself, fewer social gatherings (potentially involving alcohol
consumption) and a sense of responsibility for the pregnant partner were
reported. Of the partners, 37 % reported support for decreased drinking from
others (pregnant partner, parents, friend or workmates). Further, most partners
appreciated the midwife's counseling on alcohol. CONCLUSION: A majority of
partners decreased their alcohol consumption in transition to parenthood, which
also appears to be a crucial time for changing alcohol-drinking patterns. The
partners with higher AUDIT-C scores reported more support for decreased drinking.
Most partners appreciated the midwife's talk about alcohol and pregnancy and
those who filled out AUDIT in early pregnancy reported that the counseling was
more engaging. During pregnancy it is possible to detect partners with high
alcohol consumption, and promote interventions for decreased drinking, also for
the partners. Written information addressing alcohol use and directed to partners
is needed.
PMID- 27484751
TI - Quantum electromechanics on silicon nitride nanomembranes.
AB - Radiation pressure has recently been used to effectively couple the quantum
motion of mechanical elements to the fields of optical or microwave light.
Integration of all three degrees of freedom-mechanical, optical and microwave
would enable a quantum interconnect between microwave and optical quantum
systems. We present a platform based on silicon nitride nanomembranes for
integrating superconducting microwave circuits with planar acoustic and optical
devices such as phononic and photonic crystals. Using planar capacitors with
vacuum gaps of 60 nm and spiral inductor coils of micron pitch we realize
microwave resonant circuits with large electromechanical coupling to planar
acoustic structures of nanoscale dimensions and femtoFarad motional capacitance.
Using this enhanced coupling, we demonstrate microwave backaction cooling of the
4.48 MHz mechanical resonance of a nanobeam to an occupancy as low as 0.32. These
results indicate the viability of silicon nitride nanomembranes as an all-in-one
substrate for quantum electro-opto-mechanical experiments.
PMID- 27484752
TI - Comment on "Costs associated with emergency care and hospitalization for severe
hypoglycemia".
PMID- 27484753
TI - Reply from the authors to "Comments on 'Association of consumption of dairy
products and meat with retinal vessel calibers in subjects at increased
cardiovascular risk'".
PMID- 27484754
TI - Comments on "Impact of lifestyle interventions on depressive symptoms in
individuals at-risk of, or with, type 2 diabetes mellitus: Clinical importance of
lifestyle interventions".
PMID- 27484755
TI - The association of lean and fat mass with all-cause mortality in older adults:
The Cardiovascular Health Study.
AB - BACKGROUND AND AIMS: Understanding contributions of lean and fat tissue to
cardiovascular and non-cardiovascular mortality may help clarify areas of
prevention in older adults. We aimed to define distributions of lean and fat
tissue in older adults and their contributions to cause-specific mortality.
METHODS AND RESULTS: A total of 1335 participants of the Cardiovascular Health
Study (CHS) who underwent dual-energy x-ray absorptiometry (DEXA) scans were
included. We used principal components analysis (PCA) to define two independent
sources of variation in DEXA-derived body composition, corresponding to principal
components composed of lean ("lean PC") and fat ("fat PC") tissue. We used Cox
proportional hazards regression using these PCs to investigate the relationship
between body composition with cardiovascular and non-cardiovascular mortality.
Mean age was 76.2 +/- 4.8 years (56% women) with mean body mass index 27.1 +/-
4.4 kg/m2. A greater lean PC was associated with lower all-cause (HR = 0.91, 95%
CI 0.84-0.98, P = 0.01) and cardiovascular mortality (HR = 0.84, 95% CI 0.74
0.95, P = 0.005). The lowest quartile of the fat PC (least adiposity) was
associated with a greater hazard of all-cause mortality (HR = 1.24, 95% CI 1.04
1.48, P = 0.02) relative to fat PCs between the 25th-75th percentile, but the
highest quartile did not have a significantly greater hazard (P = 0.70).
CONCLUSION: Greater lean tissue mass is associated with improved cardiovascular
and overall mortality in the elderly. The lowest levels of fat tissue mass are
linked with adverse prognosis, but the highest levels show no significant
mortality protection. Prevention efforts in the elderly frail may be best
targeted toward improvements in lean muscle mass.
PMID- 27484756
TI - Efficacy and safety of linagliptin according to patient baseline characteristics:
A pooled analysis of three phase 3 trials.
AB - BACKGROUND AND AIMS: We aimed to determine if patient baseline characteristics
affect responses to linagliptin and identify relevant predictors of glycated
hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM).
METHODS AND RESULTS: Data were pooled from three 24-week, placebo-controlled
trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were
categorized according to baseline characteristics: age, T2DM duration, gender,
body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA
IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks
were assessed with analysis of covariance (ANCOVA). The proportion of patients
with baseline HbA1c >7% achieving HbA1c of <=7% at week 24 were evaluated.
Independent predictors of HbA1c response with linagliptin were analyzed in a
multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean
(SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (
0.42% [+/-0.11] to -0.79% [0.08]; all p < 0.001). Within subgroups, HbA1c
reduction was more pronounced in patients without MetS (-0.74% [0.06]; treatment
interaction p = 0.0489). The proportion of patients with baseline HbA1c >7%
achieving a target HbA1c <=7% was greater with linagliptin versus placebo (30.2%
vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics
significantly predicting HbA1c reductions after 24 weeks were fasting plasma
glucose and race (both p < 0.05). CONCLUSION: This post-hoc analysis supports
that linagliptin achieved clinically meaningful improvements in hyperglycemia in
patients with diverse clinical characteristics. These improvements were more
pronounced in patients without MetS.
PMID- 27484757
TI - Daytime napping, sleep duration and increased 8-year risk of type 2 diabetes in a
British population.
AB - BACKGROUND AND AIMS: Few studies have prospectively examined the relationship
between daytime napping and risk of type 2 diabetes. We aimed to study the
effects of daytime napping and the joint effects of napping and sleep duration in
predicting type 2 diabetes risk in a middle- to older-aged British population.
METHODS AND RESULTS: In 1998-2000, 13 465 individuals with no known diabetes
participating in the European Prospective Investigation into Cancer-Norfolk study
reported daytime napping habit and 24-h sleep duration. Incident type 2 diabetes
cases were identified through multiple data sources until 31 July 2006. After
adjustment for age and sex, daytime napping was associated with a 58% higher
diabetes risk. Further adjustment for education, marital status, smoking, alcohol
intake, physical activity, comorbidities and hypnotic drug use had little
influence on the association, but additional adjustment for BMI and Waist
Circumference attenuated the Odds ratio (OR) (95% CI) to 1.30 (1.01, 1.69). The
adjusted ORs (95% CI) associated with short and long sleep duration were 1.46
(1.10, 1.90) and 1.64 (1.16, 2.32), respectively. When sleep duration and daytime
napping were examined together, the risk of developing diabetes more than doubled
for those who took day naps and had less than 6 h of sleep, compared to those who
did not nap and had 6-8 h of sleep. CONCLUSION: Daytime napping was associated
with an increased risk of type 2 diabetes, particularly when combined with short
sleep duration. Further physiological studies are needed to confirm the
interaction between different domains of sleep in relation to diabetes risk.
PMID- 27484759
TI - Characterisation of the responsive properties of two running-specific prosthetic
models.
AB - BACKGROUND: The need for information regarding running-specific prosthetic
properties has previously been voiced. Such information is necessary to assist in
athletes' prostheses selection. OBJECTIVES: This study aimed to describe the
characteristics of two commercially available running-specific prostheses. STUDY
DESIGN: The running-specific prostheses were tested (in an experimental setup)
without the external interference of athlete performance variations. METHODS:
Four stiffness categories of each running-specific prosthetic model (XtendTM and
XtremeTM) were tested at seven alignment setups and three drop masses (28, 38 and
48 kg). Results for peak ground reaction force (GRFpeak), contact time ( tc),
flight time ( tf), reactive strength index (RSI) and maximal compression (Delta
L) were determined during controlled dropping of running-specific prostheses onto
a force platform with different masses attached to the experimental setup.
RESULTS: No statistically significant differences were found between the
different setups of the running-specific prostheses. Statistically significant
differences were found between the two models for all outcome variables (GRFpeak,
Xtend > Xtreme; tc, Xtreme > Xtend; tf, Xtreme > Xtend; RSI, Xtend > Xtreme;
Delta L, Xtreme > Xtend; p < 0.05). CONCLUSION: These findings suggest that the
Xtreme stores more elastic energy than the Xtend, leading to a greater
performance response. The specific responsive features of blades could guide
sprint athletes in their choice of running-specific prostheses. Clinical
relevance Insights into the running-specific prosthesis (RSP) properties and an
understanding of its responsive characteristics have implications for athletes'
prosthetic choice. Physiologically and metabolically, a short sprint event (i.e.
100 m) places different demands on the athlete than a long sprint event (i.e. 400
m), and the RSP should match these performance demands.
PMID- 27484758
TI - [Chest pain at 32 weeks' gestation: pregnancy-related spontaneous coronary artery
dissection].
AB - A 32-year-old woman at 32 weeks gestation presented with cardiac arrest due to
ventricular tachycardia following acute chest pain at home. After immediate
defibrillation with return of spontaneous circulation (ROSC), an ST segment
elevation myocardial infarction due to coronary artery dissection was confirmed.
Two drug-eluting stents were implanted and she was placed on dual antiplatelet
therapy (DAPT). The echocardiogram showed akinesis of the apex and anterior wall.
The patients risk for stent thrombosis was considered high and therefore DAPT was
continued until cesarean section at 35 weeks gestation. Intraoperatively she
received two units of packed red blood cells, one platelet concentrate, 4 g
fibrinogen and 2 g tranexamic acid. Left ventricular ejection fraction
deteriorated 8 days after delivery and the patient developed congestive heart
failure.
PMID- 27484761
TI - Self-Efficacy, Depression, and Self-Care Activities in Adult Jordanians with Type
2 Diabetes: The Role of Illness Perception.
AB - Diabetes mellitus is reaching epidemic levels worldwide. In a developing country
like Jordan, type 2 diabetes mellitus (T2DM) has reached a prevalence rate of
17.1%. This cross-sectional study examined the relationship between self-care
activities and: illness perception, depression, social support, religiosity and
spiritual coping, and self-efficacy among patients with T2DM. A random sample of
220 patients with T2DM, who attended Jordan University Hospital in Jordan were
enrolled. The data were collected through a structured interview and the medical
files. The instruments consisted of a sociodemographic and clinical standardised
questionnaires: Brief Illness Perception Questionnaire, Patients' Health
Questionnaire-9; ENRICH Social Support Instrument; Religious and Spiritual Coping
Subscale; Diabetes Management Self-Efficacy Scale; and Summary of Diabetes Self
Care Activities. Bivariate analysis investigated the relationship between
variables. Structure Equation Modelling (SEM) was performed to test the proposed
conceptual model. The study found that approximately 70% of the respondents
suffered some form of depressive symptoms. The SEM showed a direct relationship
between self-efficacy and self-care activities (beta = 0.40; p < 0.001).
Depression was indirectly related to self-care activities through self-efficacy
(beta = -0.20; p = 0.003); nevertheless, it was directly related to perception
of: treatment control, consequences, and emotional representations. Overall, the
sequence between illness perception and self-efficacy was mediated by depression.
Strategies to promote self-efficacy and illness perception are vital in
customising a diabetes health plan to meet Arabic cultural expectations.
PMID- 27484760
TI - Integrating emotional and psychological support into the end-stage renal disease
pathway: a protocol for mixed methods research to identify patients' lower-level
support needs and how these can most effectively be addressed.
AB - BACKGROUND: As a result of difficulties related to their illness, diagnosis and
treatment, patients with end-stage renal disease experience significant emotional
and psychological problems, which untreated can have considerable negative impact
on their health and wellbeing. Despite evidence that patients desire improved
support, management of their psychosocial problems, particularly at the lower
level, remains sub-optimal. There is limited understanding of the specific
support that patients need and want, from whom, and when, and also a lack of data
on what helps and hinders renal staff in identifying and responding to their
patients' support needs, and how barriers to doing so might be overcome. Through
this research we therefore seek to determine what, when, and how, support for
patients with lower-level emotional and psychological problems should be
integrated into the end-stage renal disease pathway. METHODS/DESIGN: The research
will involve two linked, multicentre studies, designed to identify and consider
the perspectives of patients at five different stages of the end-stage renal
disease pathway (Study 1), and renal staff working with them (Study 2). A
convergent, parallel mixed methods design will be employed for both studies, with
quantitative and qualitative data collected separately. For each study, the data
sets will be analysed separately and the results then compared or combined using
interpretive analysis. A further stage of synthesis will employ data-driven
thematic analysis to identify: triangulation and frequency of themes across
pathway stages; patterns and plausible explanations of effects. DISCUSSION: There
is an important need for this research given the high frequency of lower-level
distress experienced by end-stage renal disease patients and lack of progress to
date in integrating support for their lower-level psychosocial needs into the
care pathway. Use of a mixed methods design across the two studies will generate
a holistic patient and healthcare professional perspective that is more likely to
identify viable solutions to enable implementation of timely and integrated care.
Based on the research outputs, appropriate support interventions will be
developed, implemented and evaluated in a linked follow-on study.
PMID- 27484762
TI - Schidandrin B kills tumor cells by initiating apoptosis in glioma SHG-44 cells.
AB - OBJECTIVE: To observe the proliferation inhibition, cell cycle, and apoptosis of
human glioma cell line SHG-44 treated with different concentration of Schidandrin
B and explore the effect of Schidandrin B on glioma SHG-44 cells. METHODS: Glioma
SHG-44 cells were treated with Schidandrin B (0, 50, 100 or 200 MUg/mL) for 24,
48, 72 and 96 h, and cells were treated with vehicle as control. Viability of
cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) analysis; cell cycle was examined with flow cytometry assay;
apoptosis was detected with annexin V assay. Bax and caspase-3 proteins
expression were checked by Western blot. RESULTS: MTT analysis showed that
viability of glioma SHG-44 cells significantly decreased after exposure to
Schidandrin B for the indicated time. Flow cytometry revealed that the number of
cells in the sub G1 phase was increased, however, the number of cells in G0/G1, S
and G2/M phases were decreased after treatment with 50, 100 or 200 MUg/mL
Schidandrin B, compared with the respective control group. Annexin V analysis
confirmed that apoptosis rates of the control group, 50, 100, and 200 MUg/mL
Schidandrin B group were 1.76%+/-0.47%, 13.98%+/-5.05%, 19.64%+/-5.53% and
63.28%+/-6.88% respectively, apoptotic rate increased significantly with dose
dependent manner, and apoptosis of cells were observed under the inverted
microscope after 100 MUg/mL Schidandrin B treatment. Bax and caspase-3 protein
were highly expressed in Schidandrin B group compared with the control group.
CONCLUSION: The apoptosis could be induced by different concentration of
Schidandrin B on glioma SHG-44 cells, and the mechanism may be directly excited
by Schidandrin B in glioma SHG-44 cells through activating mitochondrial pathway.
PMID- 27484763
TI - Clinical observation of Shuanghuang Shengbai Granule () on prevention and
treatment of myelosuppression caused by chemotherapy in cancer patients.
AB - OBJECTIVE: To study the efficacy and safety of Shuanghuang Shengbai Granule (,
SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer
patients caused by chemotherapy. METHODS: A total of 330 patients were randomly
assigned to the treatment group (220 cases, analysed 209 cases) and the control
group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The
patients in the treatment group at the first day of chemotherapy started to take
SSG for 14 days, while the patients in the control group took Leucogon Tablets.
The changes of the blood routine, clinical symptoms and immune function in both
groups were observed for safety and efficacy evaluation. RESULTS: At the 7th day
of chemotherapy, the white blood cells (WBCs) level in the treatment group was
significantly higher than that in the control group (P<0.05). After treatment,
the WBCs rate in the normal range accounted for 50.2% in the treatment group, the
myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7%
of patients emerged grade III and grade IV myelosuppression, respectively. The
incidence of myelosuppression of the treatment group was significantly lower than
that of the control group (P<0.05). The total effective rate of Chinese medicine
syndrome in the treatment group was significantly higher than that in the control
group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were
maintained in the normal range. Compared with that before treatment, the levels
of CD3+ and CD4+ cells were significantly increased in the treatment group after
treatment (P<0.05). The discrepancy of CD3+ and CD4+ cell activity before and
after treatment in both groups were significantly different (P<0.05). No obvious
adverse event occurred in both groups. CONCLUSION: SSG had a protection effect on
bone marrow suppression, and alleviated the clinical symptoms together with
clinical safety.
PMID- 27484764
TI - Chinese medicine as complementary therapy for female infertility.
AB - Chinese medicine (CM) has been used in clinical treatment for thousands of years
in China, Japan, Korea, and other countries. CM is at present attracting many
attentions around the world for reproductive health care and disease prevention,
including treatment of female infertility. This review focuses on the CM
treatment for female infertility patients, and supplies a summary on the
efficacy, safety, and mechanism of some Chinese herbal medicines, herbal medicine
derived active compounds, and acupuncture. A large number of researches have
reported that CM could alleviate or even cure female infertility by regulating
hormone, improving reproductive outcome of in vivo fertilization, affecting
embryonic implantation, curing polycystic ovarian syndrome, endometriosis, pelvic
inflammatory disease, relieving mental stress, and regulating immune system.
Meanwhile, a few studies claimed that there was little adverse reaction of CM in
randomized controlled trials. However, up to present there is a lack of adequate
evidences with molecular mechanistic researches and randomized controlled trials
to prove the CM as an effective and safe treatment for infertility. Thus, utility
of CM as a complementary medicine will be a feasible method to improve the
outcome of female infertility treatment.
PMID- 27484765
TI - Is manipulative therapy clinically necessary for relief of neck pain? A
systematic review and meta-analysis.
AB - OBJECTIVE: To summarize and critically assess the effificacy of Eastern and
Western manipulative therapies for the treatment of neck pain in adults. METHODS:
A search of PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials,
ClinicalTrials.gov, EMBASE, etc. from their inception date to January 2014 with
Chinese, Japanese, and Korean databases. Two reviewers independently selected
randomized controlled trials (RCTs) with negative control or blank control,
extracted data and assessed methodological quality. Meta-analysis and levels of
evidence were performed by Revman5.1 and Grades of Recommendations Assessment,
Development and Evaluation (GRADE) approach. RESULTS: Nineteen clinical trials
with adequate randomization were included in this review, 11 of them had a low
risk of bias. The primary outcome for short-term pain had no significant
differences, however, the secondary outcome, only the Numerical Pain Rating Scale
(NPRS) score of intermediate-term [n=916, pooled mean differences (MD) =-0.29,
P=0.02], the Neck Disability Index (NDI) score of short-term (n=1,145, pooled MD=
2.10, P<0.01), and intermediate-term (n=987, pooled MD=-1.45, P=0.01) were
signifificantly reduced with moderate quality evidence. However, it supported the
minimally clinically important difference (MCID) of the Visual Analogue Scale and
NPRS pain score to be 13 mm, while NDI was 3.5 points. The meta-analysis only
suggested a trend in favor of manipulative therapy rather than clinical
signifificance. CONCLUSIONS: The results do not support the existing evidences
for the clinical value of Eastern or Western manipulative therapy for neck pain
of short-term follow-up according to MCIDs. The limitations of our review related
to blinding, allocation concealment and small sample size.
PMID- 27484766
TI - Efficacy of Aidi Injection () on overexpression of P-glycoprotein induced by
vinorelbine and cisplatin regimen in patients with non-small cell lung cancer.
AB - OBJECTIVE: To investigate the efficacy of Aidi Injection () on overexpression of
P-glycoprotein (P-gp) induced by vinorelbine and cisplatin (NP) regimen in
patients with non-small cell lung cancer (NSCLC), and study the difference
between intravenous administration and targeting intratumor administration of
Aidi Injection with thoracoscope. METHODS: Totally 150 patients with NSCLC were
randomly assigned to the control group, the intravenous group and the intratumor
group by the random envelope method, 50 cases in each group. The patients were
treated with NP regimen (2 cycles), NP regimen (2 cycles) plus Aidi intravenous
injection, or NP regimen (2 cycles) plus Aidi intratumor injection with
thoracoscope, respectively for 6 weeks. The clinical effificacy was observed
based on Response Evaluation Criteria in Solid Tumors (RECIST) rules, the
expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after
treatment, the safety was evaluated by monitoring the toxicity in the process of
treatment, and the progression-free survival (PFS) was measured. RESULTS: Fifteen
cases dropped out because of the irreconcilable conditions which had no
relationship with the treatment, 4 in the control group, 5 in the intravenous
group, and 6 in the intratumor group, respectively. Compared with the control
group, the response rates (complete remission + partial response) and the disease
control rates (complete remission + partial response + stable disease) were
significantly higher, the P-gp expressions were significantly decreased after 3
and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were
significantly longer in the intravenous and intratumor groups (P<0.05 or P<0.01),
and the intratumor group showed better effects than the intravenous group (P<0.05
or P<0.01). Compared with the control group, the occurrences of rash, nausea and
leukocytopenia were signifificantly decreased in the intravenous and intratumor
groups (P<0.05), but without signifificant difference between the intravenous and
intratumor groups (P>0.05). CONCLUSION: Aidi Injection not only improves the
effificacy of NP regime, but also has the function of reducing adverse events and
preventing against overexpression of P-gp induced by chemotherapy of NP regimen.
PMID- 27484767
TI - Ethanol extract of Phellinus merrillii protects against diethylnitrosamine- and 2
acetylaminofluorene-induced hepatocarcinogenesis in rats.
AB - OBJECTIVE: To study whether the ethanol extract of Phellinus merrillii (EPM) has
chemopreventive potential against liver carcinogenesis. METHODS: Thirty male
Spraque-Dawley rats were randomly divided into control group, EPM control group,
hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in
each group. Using the Solt and Farber protocol in a rat model of
hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine
(DEN)-initiated, 2-acetylaminofluorene (2-AAF) and partial hepatectomy (PH)
promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and
histological examinations, together with the serum levels of glutamic oxaloacetic
transaminase (sGOT), glutamic pyruvic transaminase (sGPT) and gamma-glutamyl
transpeptidase (gamma-GT) were measured. RESULTS: Treatment of EPM at the
concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the
development of carcinogenesis and reduced the levels of sGOT, sGPT, and serum
gamma-GT of rats as compared with the hepatocarcinoma control group (P<0.05 or
P<0.01). These phenotypes were accompanied by a significant increase in natural
killer cell activity. CONCLUSION: EPM showed a strong liver preventive effect
against DEN+2-AAF+PH-induced hepatocarcinogenesis in a rat model.
PMID- 27484768
TI - Inhibitory effects of an aqueous extract from Cortex Phellodendri on the growth
and replication of broad-spectrum of viruses in vitro and in vivo.
AB - BACKGROUND: Cortex Phellodendri (C. Phellodendri), the dried trunk bark of
Phellodendron amurense Ruprecht, has been known as a traditional herbal medicine,
showing several bioactivities. However, antiviral activity of C. Phellodendri
aqueous extract (CP) not reported in detail, particularly aiming the prophylactic
effectiveness. METHODS: In vitro CP antiviral activity evaluated against
Influenza A virus (PR8), Vesicular Stomatitis Virus (VSV), Newcastle Disease
Virus (NDV), Herpes Simplex Virus (HSV), Coxsackie Virus (H3-GFP) and Enterovirus
71 (EV-71) infection on immune (RAW264.7) and epithelial (HEK293T/HeLa) cells.
Such antiviral effects were explained by the induction of antiviral state which
was determined by phosphorylation of signal molecules, secretion of IFNs and
cytokines, and cellular antiviral mRNA expression. Furthermore, Compounds present
in the aqueous fractions confirmed by HPLC analysis and evaluated their anti
viral activities. Additionally, in vivo protective effect of CP against divergent
influenza A subtypes was determined in a BALB/c mouse infection model. RESULTS:
An effective dose of CP significantly reduced the virus replication both in
immune and epithelial cells. Mechanically, CP induced mRNA expression of anti
viral genes and cytokine secretion in both RAW264.7 and HEK293T cells.
Furthermore, the main compound identified was berberine, and shows promising
antiviral properties similar to CP. Finally, BALB/c mice treated with CP
displayed higher protection levels against lethal doses of highly pathogenic
influenza A subtypes (H1N1, H5N2, H7N3 and H9N2). CONCLUSION: CP including
berberine play an immunomodulatory role with broad spectrum antiviral activity,
due to induction of antiviral state via type I IFN stimulation mechanism.
Consequently, C. Phellodendri could be a potential source for promising natural
antivirals or to design other antiviral agents for animal and humans.
PMID- 27484769
TI - A Regional Outbreak of Clostridium difficile PCR-Ribotype 027 Infections in
Southeastern France from a Single Long-Term Care Facility.
AB - OBJECTIVE To describe and analyze a large outbreak of Clostridium difficile 027
(CD-027) infections. METHODS Confirmed CD-027 cases were defined as CD infection
plus real-time polymerase chain reaction assay (PCR) positive for CD-027.
Clinical and microbiological data on patients with CD-027 infection were
collected from January 2013 to December 2015 in the Provence-Alpes-Cote-d'Azur
region (southeastern France). RESULTS In total, 19 healthcare facilities reported
144 CD-027 infections (112 confirmed and 32 probable CD-027 infections) during a
22-month period outbreak. Although the incidence rate per 10,000 bed days was
lower in long-term care facilities (LTCFs) than in acute care facilities (0.05 vs
0.14; P<.001), cases occurred mainly in LTCFs, one of which was the probable
source of this outbreak. After centralization of CD testing, the rate of
confirmed CD-027 cases from LTCFs or residential-care homes increased
significantly (69% vs 92%; P<.001). Regarding confirmed CD-027 patients, the sex
ratio and the median age were 0.53 and 84.2 years, respectively. The 30-day crude
mortality rate was 31%. Most patients (96%) had received antibiotics within 3
months prior to the CD colitis diagnosis. During the study period, the rate of
patients with CD-027 (compared with all patients tested in the point-of-care
laboratories) decreased significantly (P=.03). CONCLUSIONS A large CD-027
outbreak occurred in southeastern France as a consequence of an initial cluster
of cases in a single LTCF. Successful interventions included rapid isolation and
testing of residents with potentially infectious diarrhea and cohorting of case
patients in a specialized infectious diseases ward to optimize management. Infect
Control Hosp Epidemiol 2016;1-5.
PMID- 27484770
TI - Kyphoscoliosis peptidase (KY) mutation causes a novel congenital myopathy with
core targetoid defects.
PMID- 27484771
TI - The expression of monocarboxylate transporters in thyroid carcinoma can be
associated with the morphological features of BRAF V600E mutation.
AB - BRAF V600E mutation, usually performed by DNA techniques, is one of the most
common diagnostic markers in papillary thyroid carcinoma. Few papers have
demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid
carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological
features of BRAF V600E on papillary thyroid carcinomas. These features seem to be
linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are
hypothesized to have a dominant role as lactate transporters. We investigated the
association between these morphological features and monocarboxylate transporters
1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy
favoring papillary thyroid carcinoma". These cases were processed with liquid
based cytology and underwent BRAF V600E mutational analysis (pyrosequencing) on
liquid-based cytology and monocarboxylate transporters immunostaining on
histology. The expression of monocarboxylate transporter 1, monocarboxylate
transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi
quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated
and 15 wild type cases showed 100 % cyto-histological concordance. The
cytological evaluation revealed plump cells and sickle nuclear shape in 100 %
mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the
mutated cases especially in both the plump cells and sickle-shaped nuclei,
whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p =
0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated
and 40 % in wild types (p < 0.005). Furthermore, 20 % of the wild types showed
weak monocarboxylate transporter 1 nuclear expression associated to a less
aggressive behavior. The analysis of glucose trasporter-1 and carbonic anhidrase
did not highlight any statistical significance (p > 0.05). This is the first
report analyzing the association between monocarboxylate transporter expression
and the morphological features of BRAF V600E mutated papillary thyroid carcinomas
suggesting the possible involvement of lactate in the morphological features.
PMID- 27484772
TI - Metabolic implications of menstrual cycle length in non-hyperandrogenic women
with polycystic ovarian morphology.
AB - This cross-sectional study aimed to investigate the association between menstrual
cycle lenght and metabolic parameters in non-hyperandrogenic women with
polycystic ovarian morphology, n = 250. Metabolic profiles of all participants
were evaluated using anthropometric parameters (body mass index, waist
circumference), parameters of dyslipidemia (total cholesterol, HDL-cholesterol,
triglycerides) and markers of insulin resistance (fasting insulin, homeostasis
model assessment for insulin resistance index). The associations between
menstrual cycle lenght and cardiometabolic risk factors such as insulin
resistance, dyslipidemia, and obesity were investigated. In non-hyperandrogenic
women with polycystic ovarian morphology, menstrual cycle lenght was associated
with hypertriglyceridemia and insulin resistance independently of body mass
index. Moreover, menstrual cycle lenght added value to body mass index in
predicting hypertriglyceridemia. The optimal menstrual cycle lenght cut-off value
for identifying of non-hyperandrogenic women with polycystic ovarian morphology
at metabolic risk was found to be 45 days. Metabolic profile of non
hyperandrogenic women with polycystic ovarian morphology (n = 75) with menstrual
cycle lenght >45 days was similar to that of hyperandrogenic women with
polycystic ovarian morphology (n = 138) while metabolic profile of non
hyperandrogenic women with polycystic ovarian morphology with menstrual cycle
lenght <=45 days (n = 112) was similar to that of controls (n = 167). Non
hyperandrogenic women with polycystic ovarian morphology with menstrual cycle
lenght >45 days had higher prevalence of cardiometabolic risk factors compared to
those with menstrual cycle lenght <=45 days. Non-hyperandrogenic women with
polycystic ovarian morphology are not metabolically homogeneous. Menstrual cycle
lenght is an easy-to-obtain clinical parameter positively associated with the
probability of unfavorable metabolic status in non-hyperandrogenic women with
polycystic ovarian morphology. Menstrual cycle lenght cut-off value of 45 days
was found to have the best capacity in discriminating non-hyperandrogenic women
with polycystic ovarian morphology with and without metabolic derangement(s)
corroborating in favor of the cardiometabolic risk factors screening and
management in non-hyperandrogenic women with polycystic ovarian morphology with
menstrual cycle lenght >45 days through strategies for prevention of
cardiovascular disease.
PMID- 27484773
TI - Infectious diseases and immunological responses in adult subjects with lifetime
untreated, congenital GH deficiency.
AB - Growth hormone is important for the development and function of the immune
system, but there is controversy on whether growth hormone deficiency is
associated to immune disorders. A model of isolated growth hormone deficiency may
clarify if the lack of growth hormone is associated with increased susceptibility
to infections, or with an altered responsiveness of the immune system. We have
studied the frequency of infectious diseases and the immune function in adults
with congenital, untreated isolated growth hormone deficiency. In a cross
sectional study, 35 adults with isolated growth hormone deficiency due to a
homozygous mutation in the growth hormone releasing hormone receptor gene and 31
controls were submitted to a clinical questionnaire, physical examination
serology for tripanosomiasis, leishmaniasis, HIV, tetanus, hepatitis B and C, and
serum total immunoglobulin G, M, E and A measurement. The immune response was
evaluated in a subset of these subjects by skin tests and response to vaccination
for hepatitis B, tetanus, and bacillus Calmette-Guerin. There was no difference
between the groups in history of infectious diseases and baseline serology.
Isolated growth hormone deficiency subjects had lower total IgG, but within
normal range. There was no difference in the response to any of the vaccinations
or in the positivity to protein Purified Derived, streptokinase or candidin.
Adult untreated isolated growth hormone deficiency does not cause an increased
frequency of infectious diseases, and does not alter serologic tests, but is
associated with lower total IgG levels, without detectable clinical impact.
PMID- 27484774
TI - Role and regulation of ferritin-like proteins in iron homeostasis and oxidative
stress survival of Caulobacter crescentus.
AB - Iron is an essential nutrient that is poorly available to living organisms but
can be harmful when in excess due to the production of reactive oxygen species.
Bacteria and other organisms use iron storage proteins called ferritins to avoid
iron toxicity and as a safe iron source in the cytosol. The alpha-proteobacterium
Caulobacter crescentus has two putative ferritins, Bfr and Dps, and some other
proteins belonging to the ferritin-like superfamily, among them the one encoded
by CC_0557. In this work, we have analyzed the role and regulation of these three
putative ferritin-like proteins. Using lacZ-transcriptional fusions, we found
that bfr expression is positively regulated (2.5-fold induction) by the Fe
responsive regulator Fur in iron sufficiency, as expected for an iron storage
protein. Expression of dps was induced 1.5-fold in iron limitation in a Fur
independent manner, while the expression of the product of CC_0557 was unaffected
by either iron supply or Fur. With respect to growth phase, while bfr expression
was constant during growth, expression of dps (1.4-fold) and CC_0557 (around
seven times) increased in the transition from exponential to stationary phase.
Deletion mutant strains for each gene and a double dps/bfr mutant were obtained
and tested for oxidative stress resistance. The dps mutant was very sensitive to
H2O2, and this phenotype was not relieved by the addition of the iron chelator
2',2-dipyridyl in the conditions tested. While bfr and CC_0557 showed no
phenotype as to H2O2 resistance, the double dps/bfr mutant had a similar
phenotype to the dps mutation alone. These findings indicate that in C.
crescentus Bfr contributes to iron homeostasis and Dps has a role in protection
against oxidative stress. The role of the protein CC_0557 containing a ferritin
like fold remains unclear.
PMID- 27484776
TI - Understanding body representations.
PMID- 27484775
TI - Linking patients with community resources: use of a free YMCA membership among
low-income black women.
AB - Given the increasing interest in expanding obesity prevention efforts to cover
community-based programs, we examined whether individuals would access a YMCA for
physical activity promotion. We provided a no-cost 12-month YMCA membership to
socioeconomically disadvantaged black women who were randomized to the
intervention arm of a weight gain prevention trial (n = 91). Analyses examined
associations of membership activation and use with baseline psychosocial,
contextual, health-related, and sociodemographic factors. Many participants (70.3
%) activated their memberships; however, use was low (42.2 % had no subsequent
visits, 46.9 % had one to ten visits). There were no predictors of membership
activation, but individuals living below/borderline the federal poverty line were
more likely to use the center (1+ visits), as were those who met physical
activity guidelines at baseline. More comprehensive and intensive interventions
may be necessary to promote use of community resources-even when provided free
among high-risk populations of women with obesity that live in rural areas of the
USA.
PMID- 27484777
TI - Primary Care Behavioral Health Provider Training: Systematic Development and
Implementation in a Large Medical System.
AB - The expansion of integrated, collaborative, behavioral health services in primary
care requires a trained behavioral health workforce with specific competencies to
deliver effective, evidence-informed, team-based care. Most behavioral health
providers do not have training or experience working as primary care behavioral
health consultants (BHCs), and require structured training to function
effectively in this role. This article discusses one such training program
developed to meet the needs of a large healthcare system initiating widespread
implementation of the primary care behavioral health model of service delivery.
It details the Department of Defense's experience in developing its extensive BHC
training program, including challenges of addressing personnel selection and
hiring issues, selecting a model for training, developing and implementing a
phased training curriculum, and improving the training over time to address
identified gaps. Future directions for training improvements and lessons learned
in a large healthcare system are discussed.
PMID- 27484778
TI - Testing vision with angular and radial multifocal designs using Adaptive Optics.
AB - Multifocal vision corrections are increasingly used solutions for presbyopia. In
the current study we have evaluated, optically and psychophysically, the quality
provided by multizone radial and angular segmented phase designs. Optical and
relative visual quality were evaluated using 8 subjects, testing 6 phase designs.
Optical quality was evaluated by means of Visual Strehl-based-metrics (VS). The
relative visual quality across designs was obtained through a psychophysical
paradigm in which images viewed through 210 pairs of phase patterns were
perceptually judged. A custom-developed Adaptive Optics (AO) system, including a
Hartmann-Shack sensor and an electromagnetic deformable mirror, to measure and
correct the eye's aberrations, and a phase-only reflective Spatial Light
Modulator, to simulate the phase designs, was developed for this study. The
multizone segmented phase designs had 2-4 zones of progressive power (0 to +3D)
in either radial or angular distributions. The response of an "ideal observer"
purely responding on optical grounds to the same psychophysical test performed on
subjects was calculated from the VS curves, and compared with the relative visual
quality results. Optical and psychophysical pattern-comparison tests showed that
while 2-zone segmented designs (angular & radial) provided better performance for
far and near vision, 3- and 4-zone segmented angular designs performed better for
intermediate vision. AO-correction of natural aberrations of the subjects
modified the response for the different subjects but general trends remained. The
differences in perceived quality across the different multifocal patterns are, in
a large extent, explained by optical factors. AO is an excellent tool to simulate
multifocal refractions before they are manufactured or delivered to the patient,
and to assess the effects of the native optics to their performance.
PMID- 27484780
TI - Acid Fast Property of Histoplasma: A Concept Revitalized.
PMID- 27484779
TI - Control of fibrotic changes through the synergistic effects of anti-fibronectin
antibody and an RGDS-tagged form of the same antibody.
AB - TGF-beta and myofibroblasts play a key role in fibrosis, characterized by
aberrant synthesis and deposition of extracellular matrix (ECM) proteins, such as
fibronectin (Fn) and collagen type I. There are two major roles played by
integrins in the fibrotic pathology: (i) Fn-integrin interaction, coupled with
cytokines like TGF-beta, facilitates the self-polymerization of Fn and regulates
cell-matrix fibrillar adhesions, thereby promoting fibrillogenesis; (ii) Integrin
interaction with an RGD (arginine-glycine-aspartic) consensus sequence in the
latent TGF-beta, resulting in its activation. This study describes an anti
fibrotic strategy using a combination of two antibodies: Fn52 (targeted against
the N-terminal 30 kDa region of fibronectin, a major site for Fn self
association), and its engineered form, Fn52RGDS (which binds to integrins).
Interestingly, a synergistic effect of the cocktail in causing a decline in
fibrotic features was confirmed in the context of fibrotic posterior capsular
opacification (PCO), mediated by the lens epithelial cells (left behind after
cataract surgery). Inclusion of Fn52RGDS to Fn52 aids in better diffusion of the
antibodies; such combination therapies could be useful in the context of
pathologies involving extensive remodeling of the fibronectin matrix, where the
thick ECM offers a major challenge for efficient drug delivery.
PMID- 27484781
TI - Parenthood, Child Care, and Heroin Use: Outcomes After Three Years.
AB - BACKGROUND: Internationally there is a lack of measurement on the impact of
childcare on people who use drugs. OBJECTIVES: The aim of this article was to
longitudinally measure drug use, familial and social status and criminal
involvement between parents and nonparents who use heroin and have children in
their care. METHODS: From 2003 to 2006, 404 participants were recruited to the
Research Outcome Study in Ireland Evaluating Drug Treatment Effectiveness (ROSIE)
as part of a longitudinal cohort study design. Participants completed the
Maudsley Addiction Profile and 88% (n = 356) completed interviews at the 3-year
period. One way between groups ANOVA with post hoc tests and backward, stepwise
multiple regression were employed for analysis. RESULTS: At follow-up, parents
who had children in their care used heroin (p = .004), illicit methadone (p <=
.001) and cocaine (p = .024) on fewer days than those who had no children, or
those who had children but did not have children in their care. These differences
were not observed at intake. Living with someone at intake who used drugs was
found to be significantly associated with increased heroin (p <= .001),
benzodiazepine (p = .039), and tobacco (p = .030) use at 3 years. Furthermore, a
change in childcare status to caring for a child was associated with increased
cannabis use (p = .025). Conclusion/Importance: While caring for children was
associated with reduced heroin use at 3 years, living with a person who used at
intake removed this effect, thus indicating that while individual based addiction
theories reflected observed outcomes, social network connectedness was more
influential.
PMID- 27484782
TI - A single-blind, dose escalation, phase I study of high-fluence light-emitting
diode-red light (LED-RL) on human skin: study protocol for a randomized
controlled trial.
AB - BACKGROUND: Skin fibrosis is involved in a variety of pathologic conditions
ranging from scar formation secondary to surgery or trauma to immune-mediated
processes. Skin fibrosis is a significant international health problem with an
estimated incidence of greater than 100 million people affected per year
worldwide with few effective treatment options available. Preliminary in vitro
data generated by our research group suggests that red light can function as a
stand-alone treatment for skin fibrosis. To our knowledge, no prior clinical
trials have been performed to determine the safety of high-fluence (dose) light
emitting diode-red light (LED-RL) phototherapy. The goal of this study is to
evaluate the safety of LED-RL fluences from 160 J/cm(2) up to 640 J/cm(2) in
healthy subjects. METHODS/DESIGN: This is a single-blind, dose escalation,
randomized controlled, phase I study to evaluate the safety of high-fluence LED
RL on human skin. The protocol for dose escalation requires subjects be enrolled
sequentially in groups of five. Within each group, three subjects will be
randomized to LED-RL phototherapy and two subjects randomized to mock therapy.
Subjects in group 1 randomized to LED-RL phototherapy will receive the maximum
recommended starting dose (160 J/cm(2)). LED-RL dose will be escalated in
subsequent groups (320 J/cm(2), 480 J/cm(2) and 640 J/cm(2)). The maximally
tolerated dose (MTD) is defined as the dose level below the dose producing
unacceptable but reversible toxicity and is considered to be the upper limit of
subject tolerance. After either a MTD has been established, or the study endpoint
of 640 J/cm(2) has been achieved, an additional 27 LED-RL phototherapy subjects
(for a total of 30) and 18 mock therapy subjects (for a total of 20) (determined
randomly) will be enrolled. Each subject will receive a total of nine procedures,
three times per week for three consecutive weeks. DISCUSSION: This study may
provide important safety information on the effects of high-fluence LED-RL
phototherapy on human skin and help facilitate future phase II studies to
evaluate the efficacy of high-fluence LED-RL as a potential noninvasive, safe,
portable, at-home therapy for treatment of skin fibrosis. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02630303 . Registered on 9 December 2015.
PMID- 27484783
TI - Dexmedetomidine versus remifentanil for sedation during awake intubation using a
Shikani optical stylet: a randomized, double-blinded, controlled trial.
AB - BACKGROUND: The purpose of this study was to compare the efficacy and safety of
dexmedetomidine versus remifentanil for sedation during awake intubation using a
Shikani optical stylet (SOS). METHODS: Sixty-eight patients with cervical trauma
or severe cervical spondylosis undergoing cervical spinal surgery were enrolled
in this prospective study. They were randomly assigned to receive dexmedetomidine
(Group D) or remifentanil (Group R). In Group D, the patients received an
intravenous loading dose of dexmedetomidine 1 MUg . kg(-1) over 10 min followed
by a continuous infusion of 0.7 MUg . kg(-1) . h(-1). In Group R, a target
controlled infusion of remifentanil was administered to achieve a plasma
concentration of 2.5 ng . ml(-1), increased to 3 ng . ml(-1) 10 min later. An
endotracheal tube was inserted using a SOS under dexmedetomidine or remifentanil
sedation after topical anesthesia to the airway. Midazolam was given as rescue
sedation. We recorded the first attempt intubation success rate, the dose of
midazolam, duration of intubation, Ramsay Sedation Scale (RSS) score, tracheal
tube tolerance score, duration of drug infusion, adverse events and patient
satisfaction score. RESULTS: The RSS score was significantly higher in Group D
than in Group R. First attempt success rate, rescue midazolam dose and the
duration of intubation did not differ between the groups. Patients in Group R
were significantly more tolerant of the tracheal tube. The incidence of hypoxia
was significantly higher in Group R than Group D, but there was no significant
difference in the incidence of other adverse events between the groups. The
hemodynamic responses of the two groups were similar, but more patients in Group
R were able to recall airway instrumentation. CONCLUSIONS: Both dexmedetomidine
and remifentanil are effective sedatives for awake intubation using an SOS.
Although the first attempt success rates were similar, patients sedated with
remifentanil tolerated the tracheal tube better after intubation with moderately
increased risk of desaturation. TRIAL REGISTRATION: www.chictr.org.cn ; ChiCTR
TRC-13003052 (February 4th, 2013).
PMID- 27484784
TI - Activating Transcription Factor 4 (ATF4)-ATF3-C/EBP Homologous Protein (CHOP)
Cascade Shows an Essential Role in the ER Stress-Induced Sensitization of
Tetrachlorobenzoquinone-Challenged PC12 Cells to ROS-Mediated Apoptosis via Death
Receptor 5 (DR5) Signaling.
AB - Tetrachlorobenzoquinone (TCBQ) is a downstream metabolite of pentachlorophenol
(PCP). Previously, we demonstrated that TCBQ caused cytotoxicity due to
mitochondrial-related apoptosis. Here, we confirmed the upregulation of death
receptor 5 (DR5) followed by the construction of the death-inducing signaling
complex (DISC). We also detected the activation of the caspase cascade, which was
correlated with TCBQ-induced apoptotic cell death in PC12 cells. The upregulation
of DR5 included transcriptional activation and de novo protein synthesis in
response to TCBQ. We also identified the endoplasmic reticulum (ER) as a new
target for the TCBQ challenge in PC12 cells. The protein kinase R-like ER
kinase/eukaryotic translation initiation factor 2alpha (PERK/eIF2alpha)-mediated
activating transcription factor 4 (ATF4)-ATF3-C/EBP homologous protein (CHOP)
signaling pathway contributed to the process of TCBQ-induced ER stress. Blocking
ATF4, ATF3, or CHOP signaling by gene silencing technology resulted in decreased
cell apoptosis after exposure to TCBQ. Finally, NAC ameliorated TCBQ-induced
apoptosis and ER stress, which illustrated that TCBQ-induced apoptosis is somehow
ROS-dependent. In summary, this study provided important mechanistic insight into
how TCBQ utilizes ER stress-related signaling to exhibit pro-apoptotic activity
in PC12 cells.
PMID- 27484785
TI - Renal ischemia/reperfusion against nephrectomy for induction of acute lung injury
in rats.
AB - PURPOSE: Acute kidney injury (AKI) induces acute lung injury (ALI) through
releasing injurious mediators or impairing clearance of systemic factors. To
determine the links between AKI and ALI, pulmonary and blood variables were
evaluated following induction of AKI via different experimental models of
bilateral renal ischemia/reperfusion (BIR: renal ischemia with uremia),
unilateral renal ischemia/reperfusion (UIR: renal ischemia without uremia),
bilateral nephrectomy (BNX: uremia without renal ischemia), and unilateral
nephrectomy (UNX: without uremia and renal ischemia). METHODS: Ninety male
Sprague-Dawley rats were divided into six groups. Animals had 1-h bilateral or 2
h unilateral renal ischemia followed by 24-h reperfusion in the BIR and UIR
groups, respectively, and 24-h period following bilateral or unilateral
nephrectomy in the BNX and UNX groups, respectively. There were also sham and
control groups with and without sham-operation, respectively. RESULTS: Plasma
malondialdehyde and nitric oxide were elevated by BIR more than UIR, but not
changed by UNX and BNX. UIR slightly increased plasma creatinine, whereas BIR and
BNX largely increased plasma creatinine, urea, K+ and osmolality and decreased
arterial HCO3-, pH, and CO2. UNX and UIR did not affect lung, but BIR and BNX
induced ALI with equal capillary leak and macrophages infiltration. However,
there were more prominent lung edema and vascular congestion following BNX and
more severe neutrophils infiltration and PaO2/FiO2 reduction following BIR.
CONCLUSION: Acutely accumulated systemic mediators following renal failure in the
absence of kidneys vary from those due to combined renal failure with ischemic
reperfused kidneys and consequently they induce ALI with distinct
characteristics.
PMID- 27484787
TI - Enzyme-mediated polymerization inside engineered protein cages.
AB - Engineered variants of the capsid-forming enzyme lumazine synthase, AaLS, were
used as nanoreactors for an enzyme-mediated polymerization. Oxidation of 3,3
diaminobenzidine (DAB) by the engineered ascorbate peroxidase APEX2 encapsulated
in AaLS capsids resulted in templated formation of polyDAB-capsid nanoparticles
of homogeneous size and shape.
PMID- 27484786
TI - Expression of cancer related BRCA1 missense variants decreases MMS-induced
recombination in Saccharomyces cerevisiae without altering its nuclear
localization.
AB - BRCA1 tumor suppressor gene is found mutated in familial breast and ovarian
cancer. Most cancer related mutations were found located at the RING (Really
Interesting New Gene) and at the BRCT (BRca1 C-Terminal) domain. However, 20 y
after its identification, the biological role of BRCA1 and which domains are more
relevant for tumor suppression are still being elucidated. We previously reported
that expression of BRCA1 cancer related variants in the RING and BRCT domain
increases spontaneous homologous recombination in yeast indicating that BRCA1 may
interact with yeast DNA repair/recombination. To finally demonstrate whether
BRCA1 interacts with yeast DNA repair, we exposed yeast cells expressing BRCA1wt,
the cancer-related variants C-61G and M1775R to different doses of the alkylating
agent methyl methane-sulfonate (MMS) and then evaluated the effect on survival
and homologous recombination. Cells expressing BRCA1 cancer variants were more
sensitive to MMS and less inducible to recombination as compared to cell
expressing BRCA1wt. Moreover, BRCA1-C61G and -M1775R did not change their nuclear
localization form as compared to the BRCA1wt or the neutral variant R1751Q
indicating a difference in the DNA damage processing. We propose a model where
BRCA1 cancer variants interact with the DNA double strand break repair pathways
producing DNA recombination intermediates, that maybe less repairable and
decrease MMS-induced recombination and survival. Again, this study strengthens
the use of yeast as model system to characterize the mechanisms leading to cancer
in humans carrying the BRCA1 missense variant.
PMID- 27484788
TI - From Early Embryonic to Adult Stage: Comparative Study of Action Potentials of
Native and Pluripotent Stem Cell-Derived Cardiomyocytes.
AB - Cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPS-CMs) are
promising candidates for cell therapy, drug screening, and developmental studies.
It is known that iPS-CMs possess immature electrophysiological properties, but an
exact characterization of their developmental stage and subtype differentiation
is hampered by a lack of knowledge of electrophysiological properties of native
CMs from different developmental stages and origins within the heart. Thus, we
sought to systematically investigate action potential (AP) properties of native
murine CMs and to establish a database that allows classification of stem cell
derived CMs. Hearts from 129S2PasCrl mice were harvested at days 9-10, 12-14, and
16-18 postcoitum, as well as 1 day, 3-4 days, 1-2 weeks, 3-4 weeks, and 6 weeks
postpartum. AP recordings in left and right atria and at apical, medial, and
basal left and right ventricles were performed with sharp glass microelectrodes.
Measurements revealed significant changes in AP morphology during pre- and
postnatal murine development and significant differences between atria and
ventricles, enabling a classification of developmental stage and subtype
differentiation of stem cell-derived CMs based on their AP properties. For iPS
CMs derived from cell line TiB7.4, a typical ventricular phenotype was
demonstrated at later developmental stages, while there were electrophysiological
differences from atrial as well as ventricular native CMs at earlier stages. This
finding supports that iPS-CMs can develop AP properties similar to native CMs,
but points to differences in the maturation process between iPS-CMs and native
CMs, which may be explained by dissimilar conditions during in vitro
differentiation and in vivo development.
PMID- 27484789
TI - Imaging prediction of residual hepatocellular carcinoma after locoregional
therapy in patients undergoing liver transplantation or partial hepatectomy.
AB - PURPOSE: Locoregional therapies for hepatocellular carcinoma (HCC) offer
alternatives for patients unable to undergo resection or awaiting transplant. We
sought to evaluate the prevalence and interobserver agreement of imaging features
suggestive of viable tumor at posttherapy CT/MRI and to determine a size
threshold for tumor detection. METHODS: Patients having undergone liver
transplant or hepatectomy between 2012 and 2014 with presurgical embolization or
ablation of HCC were identified. Imaging was retrospectively reviewed, and
enhancement characteristics of each lesion were noted by two radiologists.
Original pathology slides were reviewed, and the size of nodular viable tumor was
noted, if present. Cohen's kappa was used to evaluate interobserver agreement.
RESULTS: 87 patients with 129 HCCs were reviewed retrospectively following IRB
approval. 50% (65/129) of lesions showed viable tumor at pathology. 86 lesions
(67%) were imaged with CT and 43 (33%) with MR. Of viable lesions, 25 (38%)
showed nodular arterial enhancement and 18 (28%) demonstrated washout. One lesion
had capsule appearance. Sensitivity/specificity for nodular enhancement, washout,
and capsule were 0.38/0.83, 0.28/0.89, and 0.02/1.00, respectively. Overall
detection rate was 41% of <1 cm, 54% of 1-2 cm, and 57% of >2 cm viable lesions.
CONCLUSIONS: Nodular arterial enhancement was most frequently observed, followed
by washout. Both showed moderate interobserver agreement. Sensitivity of any
imaging feature was less than 50%, though findings were specific for viable
disease. There is limited detection of nodules of viable tumor <1 cm and only
marginal detection of larger lesions, though MRI outperformed CT for the
detection of subcentimeter viable tumor.
PMID- 27484790
TI - Trans 18-carbon monoenoic fatty acid has distinct effects from its isomeric cis
fatty acid on lipotoxicity and gene expression in Saccharomyces cerevisiae.
AB - Epidemiological studies have suggested that an excess intake of trans-unsaturated
fatty acids increases the risk of coronary heart disease. However, the mechanisms
of action of trans-unsaturated fatty acids in eukaryotic cells remain unclear.
Since the budding yeast Saccharomyces cerevisiae can grow using fatty acids as
the sole carbon source, it is a simple and suitable model organism for
understanding the effects of trans-unsaturated fatty acids at the molecular and
cellular levels. In this study, we compared the physiological effects of Delta9
cis and trans 18-carbon monoenoic fatty acids (oleic acid and elaidic acid) in
yeast cells. The results obtained revealed that the two types have distinct
effects on the expression of OLE1, which encodes Delta9 desaturase, and
lipotoxicity in are1Deltaare2Deltadga1Deltalro1Delta and gat1Delta cells. Our
results suggest that cis and trans 18-carbon monoenoic fatty acids exert
different physiological effects in the regulation of gene expression and
processing of excess fatty acids in yeast.
PMID- 27484792
TI - Genetic Characterization of Serotypes A and Asia-1 Foot-and-mouth Disease Viruses
in Balochistan, Pakistan, in 2011.
AB - This study reports characterization of foot-and-mouth disease virus (FMDV) in
samples collected from Balochistan, Pakistan. FMDV was detected by pan-FMDV real
time RT-PCR in 31 samples (epithelial and oral swabs) collected in 2011 from
clinical suspect cases. Of these, 29 samples were serotyped by serotype-specific
real-time RT-PCR assays and were confirmed by sequencing the VP1 coding region.
Sixteen samples were found positive for serotype A and eight for serotype Asia-1,
whereas five samples were found positive for both serotypes A and Asia-1. Two
serotype A positive samples were found positive for two different strains of
serotype A FMDV each. Phylogenetic analyses of serotype A FMDVs showed
circulation of at least three different sublineages within the A-Iran05 lineage.
These included two earlier reported sublineages, A-Iran05HER-10 and A-Iran05FAR
11 , and a new sublineage, designated here as A-Iran05BAL-11 . This shows that
viruses belonging to the A-Iran05 lineage are continuously evolving in the
region. Viruses belonging to the A-Iran05FAR-11 sublineage showed close identity
with the viruses circulating in 2009 in Pakistan and Afghanistan. However,
viruses belonging to the A-Iran05HER-10 detected in Balochistan, Pakistan, showed
close identity with the viruses circulating in Kyrgyzstan, Iran and Kazakhstan in
2011 and 2012, showing that viruses responsible for outbreak in these countries
have a common origin. Serotype Asia-1 FMDVs reported in this study all belonged
to the earlier reported Group-VII (Sindh-08), which is currently a dominant
strain in the West Eurasian region. Detection of two different serotypes of FMDV
or/and two different strains of the same serotype in one animal/sample shows
complexity in occurrence of FMD in the region.
PMID- 27484791
TI - Molecular and epigenetic features of melanomas and tumor immune microenvironment
linked to durable remission to ipilimumab-based immunotherapy in metastatic
patients.
AB - BACKGROUND: Ipilimumab (Ipi) improves the survival of advanced melanoma patients
with an incremental long-term benefit in 10-15 % of patients. A tumor signature
that correlates with this survival benefit could help optimizing individualized
treatment strategies. METHODS: Freshly frozen melanoma metastases were collected
from patients treated with either Ipi alone (n: 7) or Ipi combined with a
dendritic cell vaccine (TriMixDC-MEL) (n: 11). Samples were profiled by
immunohistochemistry (IHC), whole transcriptome (RNA-seq) and methyl-DNA
sequencing (MBD-seq). RESULTS: Patients were divided in two groups according to
clinical evolution: durable benefit (DB; 5 patients) and no clinical benefit (NB;
13 patients). 20 metastases were profiled by IHC and 12 were profiled by RNA- and
MBD-seq. 325 genes were identified as differentially expressed between DB and NB.
Many of these genes reflected a humoral and cellular immune response. MBD-seq
revealed differences between DB and NB patients in the methylation of genes
linked to nervous system development and neuron differentiation. DB tumors were
more infiltrated by CD8(+) and PD-L1(+) cells than NB tumors. B cells (CD20(+))
and macrophages (CD163(+)) co-localized with T cells. Focal loss of HLA class I
and TAP-1 expression was observed in several NB samples. CONCLUSION: Combined
analyses of melanoma metastases with IHC, gene expression and methylation
profiling can potentially identify durable responders to Ipi-based immunotherapy.
PMID- 27484794
TI - Stacking fault energy of face-centered cubic metals: thermodynamic and ab initio
approaches.
AB - The formation energy of the interface between face-centered cubic (fcc) and
hexagonal close packed (hcp) structures is a key parameter in determining the
stacking fault energy (SFE) of fcc metals and alloys using thermodynamic
calculations. It is often assumed that the contribution of the planar fault
energy to the SFE has the same order of magnitude as the bulk part, and thus the
lack of precise information about it can become the limiting factor in
thermodynamic predictions. Here, we differentiate between the interfacial energy
for the coherent fcc(1 1 1)/hcp(0 0 0 1) interface and the 'pseudo-interfacial
energy' that enters the thermodynamic expression for the SFE. Using first
principles calculations, we determine the coherent and pseudo-interfacial
energies for six elemental metals (Al, Ni, Cu, Ag, Pt, and Au) and three
paramagnetic Fe-Cr-Ni alloys. Our results show that the two interfacial energies
significantly differ from each other. We observe a strong chemistry dependence
for both interfacial energies. The calculated pseudo-interfacial energies for the
Fe-Cr-Ni steels agree well with the available literature data. We discuss the
effects of strain on the description of planar faults via thermodynamic and ab
initio approaches.
PMID- 27484793
TI - Circadian variation of cytotoxicity and genotoxicity induced by an
immunosuppressive agent "Mycophenolate Mofetil" in rats.
AB - Immunosuppressive drugs such as Mycophenolate Mofetil (MMF) are used to suppress
the immune system activity in transplant patients and reduce the risk of organ
rejection. The present study investigates whether the potential cytotoxicity and
genotoxicity varied according to MMF dosing-time in Wistar Rat. A potentially
toxic MMF dose (300 mg/kg) was acutely administered by the i.p. route in rats at
four different circadian stages (1, 7, 13 and 19 hours after light onset, HALO).
Rats were sacrificed 3 days following injection, blood and bone marrow were
removed for determination of cytotoxicity and genotoxicity analysis. The
genotoxic effect of this pro-drug was investigated using the comet assay and the
micronucleus test. Hematological changes were also evaluated according to
circadian dosing time. MMF treatment induced a significant decrease at 7 HALO in
red blood cells, in the hemoglobin rate and in white blood cells. These
parameters followed a circadian rhythm in controls or in treated rats with an
acrophase located at the end of the light-rest phase. A significant,
thrombocytopenia was observed according to MMF circadian dosing time.
Furthermore, abnormally shaped red cells, sometimes containing micronuclei,
poikilocytotic in red cells and hypersegmented neutrophil nuclei were observed
with MMF treatment. The micronucleus test revealed damage to chromosomes in rat
bone marrow; the comet assay showed significant DNA damage. This damage varied
according to circadian MMF dosing time. The injection of MMF in the middle of the
dark-activity phase produced a very mild hematological toxicity and low
genotoxicity. Conversely, it induced maximum hematological toxicity and
genotoxicity when the administration occurred in the middle of the light-rest
phase, which is physiologically analogous to the end of the activity of the
diurnal phase in human patients.
PMID- 27484795
TI - Codon usage in Alphabaculovirus and Betabaculovirus hosted by the same insect
species is weak, selection dominated and exhibits no more similar patterns than
expected.
AB - Mutations shape synonymous codon usage bias in certain organism genomes, while
selection shapes it in others. Lepidopteran-specific Alphabaculovirus and
Betabaculovirus are two large genera in the family of Baculoviridae. In this
study, we analyzed the codon usage patterns in 17 baculoviruses, including 10
alphabaculoviruses and 7 betabaculoviruses, which were isolated from seven insect
species, and we characterized the codon usage patterns between Alphabaculovirus
and Betabaculovirus. Our results show that all the baculoviruses possessed a
general weak trend of codon bias. The differences of ENc (effective number of
codons) values, nucleotide contents and the impacts of nucleotide content on ENc
value within alpha-/betabaculovirus pairs were independent of whether the host
species are the same or different. Furthermore, the majority of amino acid
sequences adopted codons unequally in all viruses, but the numbers of common
preferred codons between alpha- and betabaculoviruses hosted by the same insect
species were not significantly different from the differences observed between
alpha- and betabaculoviruses hosted by different insect species. In addition, the
amino acids that adopt the same synonymous codon composition between alpha- and
betabaculoviruses hosted by the same insect species were statistically as few as
those between alpha- and betabaculoviruses hosted by different insect species.
Correspondence analysis revealed that no major factors resulted in the codon bias
in these baculoviruses, implying multiple minor influential factors exist.
Neutrality plot analysis indicated that selection pressure dominated mutations in
shaping the codon usage. However, the levels of selection pressure were not
significantly different among viruses hosted by the same insect species. We
expect that evolution would cause the alpha- and betabaculoviruses hosted by the
same insect species to share more patterns, but this effect was not observed.
PMID- 27484796
TI - Effects of cisplatin on the LSD1-mediated invasion and metastasis of prostate
cancer cells.
AB - Prostate cancer poses a major public health problem in men. Metastatic prostate
cancer is incurable, and ultimately threatens the life of patients. Lysine
specific demethylase 1 (LSD1) is an androgen receptor-interacting protein that
exerts a key role in regulating gene expression and is involved in numerous
biological processes associated with prostate cancer. Cisplatin, also known as
cis-diamminedichloroplatinum or DDP, is a standard chemotherapeutic agent used to
treat prostate cancer; however, it has the disadvantage of various serious side
effects. The present study aimed to investigate the effects of LSD1 knockdown,
and the interplay between LSD1 and DDP, on prostate cancer cell proliferation,
apoptosis and invasion, and, therefore, the potential of LSD1 as a target for
prostate cancer therapy. Flow cytometric analysis, Cell Counting kit 8 assay,
Transwell assay and western blotting results revealed that LSD1 knockdown, in
combination with DDP treatment, exerted antiproliferative, proapoptotic and anti
invasive effects on PC3 prostate cancer cells. In addition, knockdown of LSD1
acted synergistically with DDP, thereby enhancing the induction of apoptosis, and
the inhibition of proliferation and invasion in prostate cancer cells. These
results indicated that LSD1 may serve as a potential therapeutic target, and may
enhance the sensitivity of PC3 cells to DDP.
PMID- 27484797
TI - Blue Light-excited Light-Oxygen-Voltage-sensing Domain 2 (LOV2) Triggers a
Rearrangement of the Kinase Domain to Induce Phosphorylation Activity in
Arabidopsis Phototropin1.
AB - Phototropin1 is a blue light (BL) receptor in plants and shows BL-dependent
kinase activation. The BL-excited light-oxygen-voltage-sensing domain 2 (LOV2) is
primarily responsible for the activation of the kinase domain; however, the
molecular mechanism by which conformational changes in LOV2 are transmitted to
the kinase domain remains unclear. Here, we investigated BL-induced structural
changes of a minimum functional fragment of Arabidopsis phototropin1 composed of
LOV2, the kinase domain, and a linker connecting the two domains using small
angle x-ray scattering (SAXS). The fragment existed as a dimer and displayed
photoreversible SAXS changes reflected in the radii of gyration of 42.9 A in the
dark and 48.8 A under BL irradiation. In the dark, the molecular shape
reconstructed from the SAXS profiles appeared as two bean-shaped lobes in a
twisted arrangement that was 170 A long, 80 A wide, and 50 A thick. The molecular
shape under BL became slightly elongated from that in the dark. By fitting the
crystal structure of the LOV2 dimer and a homology model of the kinase domain to
their inferred shapes, the BL-dependent change could be interpreted as the
positional shift in the kinase domain relative to that of the LOV2 dimer. In
addition, we found that lysine 475, a functionally important residue, in the N
terminal region of LOV2 plays a critical role in transmitting the structural
changes in LOV2 to the kinase domain. The interface between the domains is
critical for signaling, suitably changing the structure to activate the kinase in
response to conformational changes in the adjoining LOV2.
PMID- 27484798
TI - The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3beta Interaction
Protein (GSKIP) Regulates beta-Catenin through Its Interactions with Both Protein
Kinase A (PKA) and GSK3beta.
AB - The A-kinase anchoring protein (AKAP) GSK3beta interaction protein (GSKIP) is a
cytosolic scaffolding protein binding protein kinase A (PKA) and glycogen
synthase kinase 3beta (GSK3beta). Here we show that both the AKAP function of
GSKIP, i.e. its direct interaction with PKA, and its direct interaction with
GSK3beta are required for the regulation of beta-catenin and thus Wnt signaling.
A cytoplasmic destruction complex targets beta-catenin for degradation and thus
prevents Wnt signaling. Wnt signals cause beta-catenin accumulation and
translocation into the nucleus, where it induces Wnt target gene expression.
GSKIP facilitates control of the beta-catenin stabilizing phosphorylation at Ser
675 by PKA. Its interaction with GSK3beta facilitates control of the
destabilizing phosphorylation of beta-catenin at Ser-33/Ser-37/Thr-41. The
influence of GSKIP on beta-catenin is explained by its scavenger function; it
recruits the kinases away from the destruction complex without forming a complex
with beta-catenin. The regulation of beta-catenin by GSKIP is specific for this
AKAP as AKAP220, which also binds PKA and GSK3beta, did not affect Wnt signaling.
We find that the binding domain of AKAP220 for GSK3beta is a conserved GSK3beta
interaction domain (GID), which is also present in GSKIP. Our findings highlight
an essential compartmentalization of both PKA and GSK3beta by GSKIP, and ascribe
a function to a cytosolic AKAP-PKA interaction as a regulatory factor in the
control of canonical Wnt signaling. Wnt signaling controls different biological
processes, including embryonic development, cell cycle progression, glycogen
metabolism, and immune regulation; deregulation is associated with diseases such
as cancer, type 2 diabetes, inflammatory, and Alzheimer's and Parkinson's
diseases.
PMID- 27484799
TI - Human Naa50 Protein Displays Broad Substrate Specificity for Amino-terminal
Acetylation: DETAILED STRUCTURAL AND BIOCHEMICAL ANALYSIS USING TETRAPEPTIDE
LIBRARY.
AB - Amino-terminal acetylation is a critical co-translational modification of the
newly synthesized proteins in a eukaryotic cell carried out by six amino-terminal
acetyltransferases (NATs). All NATs contain at least one catalytic subunit, and
some contain one or two additional auxiliary subunits. For example, NatE is a
complex of Naa10, Naa50, and Naa15 (auxiliary). In the present study, the crystal
structure of human Naa50 suggested the presence of CoA and acetylated
tetrapeptide (AcMMXX) that have co-purified with the protein. Biochemical and
thermal stability studies on the tetrapeptide library with variations in the
first and second positions confirm our results from the crystal structure that a
peptide with Met-Met in the first two positions is the best substrate for this
enzyme. In addition, Naa50 acetylated all MXAA peptides except for MPAA.
Transcriptome analysis of 10 genes that make up six NATs in humans from eight
different cell lines suggests that components of NatE are transcribed in all cell
lines, whereas others are variable. Because Naa10 is reported to acetylate all
amino termini that are devoid of methionine and Naa50 acetylates all other
peptides that are followed by methionine, we believe that NatE complex can be a
major contributor for amino-terminal acetylation at the ribosome exit tunnel.
PMID- 27484800
TI - Ligand-induced Epitope Masking: DISSOCIATION OF INTEGRIN alpha5beta1-FIBRONECTIN
COMPLEXES ONLY BY MONOCLONAL ANTIBODIES WITH AN ALLOSTERIC MODE OF ACTION.
AB - We previously demonstrated that Arg-Gly-Asp (RGD)-containing ligand-mimetic
inhibitors of integrins are unable to dissociate pre-formed integrin-fibronectin
complexes (IFCs). These observations suggested that amino acid residues involved
in integrin-fibronectin binding become obscured in the ligand-occupied state.
Because the epitopes of some function-blocking anti-integrin monoclonal
antibodies (mAbs) lie near the ligand-binding pocket, it follows that the
epitopes of these mAbs may become shielded in the ligand-occupied state. Here, we
tested whether function-blocking mAbs directed against alpha5beta1 can interact
with the integrin after it forms a complex with an RGD-containing fragment of
fibronectin. We showed that the anti-alpha5 subunit mAbs JBS5, SNAKA52, 16, and
P1D6 failed to disrupt IFCs and hence appeared unable to bind to the ligand
occupied state. In contrast, the allosteric anti-beta1 subunit mAbs 13, 4B4, and
AIIB2 could dissociate IFCs and therefore were able to interact with the ligand
bound state. However, another class of function-blocking anti-beta1 mAbs,
exemplified by Lia1/2, could not disrupt IFCs. This second class of mAbs was also
distinguished from 13, 4B4, and AIIB2 by their ability to induce homotypic cell
aggregation. Although the epitope of Lia1/2 was closely overlapping with those of
13, 4B4, and AIIB2, it appeared to lie closer to the ligand-binding pocket. A new
model of the alpha5beta1-fibronectin complex supports our hypothesis that the
epitopes of mAbs that fail to bind to the ligand-occupied state lie within, or
very close to, the integrin-fibronectin interface. Importantly, our findings
imply that the efficacy of some therapeutic anti-integrin mAbs could be limited
by epitope masking.
PMID- 27484802
TI - Can herbicide safeners allow selective control of weedy rice infesting rice
crops?
AB - BACKGROUND: Rice is a major field crop of paramount importance for global food
security. However, the increased adoption of more profitable and resource
efficient direct-seeded rice (DSR) systems has contributed to greater weed
infestations, including weedy rice, which has become a severe problem in several
Asian regions. In this study we have developed a conceptually novel method to
protect rice plants at high doses of clomazone and triallate. RESULTS: The
insecticide phorate applied to rice seeds provided a substantial level of
protection against the herbicides clomazone or triallate. A quantity of 15 kg
phorate ha-1 significantly increased the LD50 values, which were more than
twofold greater than for rice plants treated only with clomazone. A quantity of
20 kg phorate ha-1 in combination with 2000 g triallate ha-1 safened rice plants
(80% survival) with LD50 >3.4-fold greater than in phorate-untreated rice. Weed
control efficacy was not lowered by the presence of phorate-treated rice seeds.
CONCLUSION: Weedy rice is one of the most damaging global weeds and a major
threat to DSR systems. In this study we have developed a proof-of-concept method
to allow selective weedy rice control in rice crops. We call for herbicide
discovery programmes and research to identify candidate safener and herbicide
combinations to achieve selective herbicide control of weedy rice and alleviate
weed infestations in global rice crops. (c) 2016 Society of Chemical Industry.
PMID- 27484803
TI - Solvothermal synthesis of a silicon hierarchical structure composed of 20 nm Si
nanoparticles coated with carbon for high performance Li-ion battery anodes.
AB - A silicon hierarchical structure composed of 20 nm Si nanoparticles (Si-20) is
synthesized using a solvothermal method. After coating with a carbon layer by
pyrolysis of acetylene gas, the fabricated Si-20@C composites exhibit a superior
cycling performance with 915.8 mA h g(-1) at 3.6 A g(-1) over 500 cycles and a
high rate performance with 746.2 mA h g(-1) at 10.8 A g(-1).
PMID- 27484801
TI - Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2
positive breast cancer patients treated with chemotherapy and HER2-targeted
agents in the CherLOB trial.
AB - BACKGROUND: The aim of this work was to evaluate the impact of (and relative
contribution of) tumor-related and immune-related diversity of HER2-positive
disease on the response to neoadjuvant chemotherapy plus anti-HER2 agents.
PATIENTS AND METHODS: The CherLOB phase II study randomized 121 HER2-positive
breast cancer patients to neoadjuvant chemotherapy plus trastuzumab, lapatinib or
both. Tumor samples from diagnostic core biopsy were centralized. Tumor
infiltrating lymphocytes (TILs) were evaluated on H&E slides. Intrinsic subtyping
was carried out using the research-based 50-gene prediction analysis of a
microarray (PAM50) subtype predictor. Immune-related gene signatures were also
evaluated. RESULTS: Continuous Str-TILs and It-TILs were significantly associated
with pCR [OR 1.03, 95% CI 1.02-1.05 (P < 0.001) and OR 1.09, 95% CI 1.04-1.15 (P
< 0.001) for Str-TILs and It-TILs, respectively]. According to PAM50, the subtype
distribution was as follows: HER2-enriched 26.7%, Luminal A 25.6%, Luminal B
16.3%, Basal-like 14% and Normal-like 17.4%. The highest rate of pCR was observed
for the HER2-enriched subtype (50%), followed by Basal-like, Luminal B and
Luminal A (chi(2) test, P = 0.026). Immune gene signatures significantly
associated with pCR in univariate analyses were identified: most of them
maintained a significant association with pCR in multivariate analyses corrected
for PAM50 subtypes, whereas TILs did not. CONCLUSIONS: In this study, both tumor
related and immune-related features contribute to the modulation of pCR after
neoadjuvant chemotherapy plus anti-HER2 agents. Immune signatures rather than
TILs added significant prediction of pCR beyond PAM50 intrinsic subtypes.
PMID- 27484804
TI - Reduction, alignment and visualisation of large diverse sequence families.
AB - BACKGROUND: Current volumes of sequence data can lead to large numbers of hits
identified on a search, typically in the range of 10s to 100s of thousands. It is
often quite difficult to tell from these raw results whether the search has been
a success or has picked-up sequences with little or no relationship to the query.
The best approach to this problem is to cluster and align the resulting families,
however, existing methods concentrate on fast clustering and either do not align
the sequences or only perform a limited alignment. RESULTS: A method (MULSEL) is
presented that combines fast peptide-based pre-sorting with a following cascade
of mini-alignments, each of which are generated with a robust profile/profile
method. From these mini-alignments, a representative sequence is selected, based
on a variety of intrinsic and user-specified criteria that are combined to
produce the sequence collection for the next cycle of alignment. For moderate
sized sequence collections (10s of thousands) the method executes on a laptop
computer within seconds or minutes. CONCLUSIONS: MULSEL bridges a gap between
fast clustering methods and slower multiple sequence alignment methods and
provides a seamless transition from one to the other. Furthermore, it presents
the resulting reduced family in a graphical manner that makes it clear if family
members have been misaligned or if there are sequences present that appear
inconsistent.
PMID- 27484805
TI - Reproducibility and uptake time dependency of volume-based parameters on FDG-PET
for lung cancer.
AB - BACKGROUND: Volume-based parameters, such as metabolic tumor volume (MTV) and
total lesion glycolysis (TLG), on F-18 fluorodeoxyglucose (FDG) positron emission
tomography (PET) are useful for predicting treatment response in nonsmall cell
lung cancer (NSCLC). We aimed to examine intra- and inter-operator
reproducibility to measure the MTV and TLG, and to estimate their dependency on
the uptake time. METHODS: Fifty NSCLC patients underwent preoperative FDG-PET.
After an injection of FDG, the whole body was scanned twice: at the early phase
(61.4 +/- 2.8 min) and delayed phase (117.7 +/- 1.6 min). Two operators
independently defined the tumor boundary using three different delineation
methods: (1) the absolute SUV threshold method (MTVp and TLGp; p = 2.0, 2.5, 3.0,
3.5), (2) the fixed% SUVmax threshold method (MTVq% and TLGq%; q = 35, 40, 45),
and (3) the adaptive region-growing method (MTVARG and TLGARG). Parameters were
compared between operators and between phases. RESULTS: Both the intra- and inter
operator reproducibility were high for all parameters using any method (intra
class correlation > 0.99 each). MTV3.0 and MTV3.5 resulted in a significant
increase from the early to delayed phase (P < 0.05 for both), whereas MTV2.0 and
MTV2.5 neither increased nor decreased (P = n.s.). All of the MTVq% values
significantly decreased over time (P < 0.01), whereas MTVARG and TLG with any
delineation method increased significantly (P < 0.05). CONCLUSIONS: High
reproducibility of MTV and TLG was obtained by all of the methods used. MTV2.0
and MTV2.5 were the least sensitive to uptake time, and may be good alternatives
when we compare images acquired with different uptake times, although applying
constant uptake time is important for volume measurement.
PMID- 27484806
TI - A prognostic predictor panel with DNA methylation biomarkers for early-stage lung
adenocarcinoma in Asian and Caucasian populations.
AB - BACKGROUND: The incidence of lung adenocarcinoma (LUAD) is increasing worldwide
with different prognosis even in early-stage patients. We aimed to identify a
prognostic panel with multiple DNA methylation biomarkers to predict survival in
early-stage LUAD patients of different racial groups. METHODS: The methylation
array, pyrosequencing methylation assay, Cox regression and Kaplan-Meier analyses
were conducted to build the risk score equations of selected probes in a training
cohort of 69 Asian LUAD patients. The risk score model was verified in another
cohort of 299 Caucasian LUAD patients in The Cancer Genome Atlas (TCGA) database.
RESULTS: We performed a Cox regression analysis, in which the regression
coefficients were obtained for eight probes corresponding to eight genes (AGTRL1,
ALDH1A3, BDKRB1, CTSE, EFNA2, NFAM1, SEMA4A and TMEM129). The risk score was
derived from sum of each methylated probes multiplied by its corresponding
coefficient. Patients with the risk score greater than the median value showed
poorer overall survival compared with other patients (p = 0.007). Such a risk
score significantly predicted patients showing poor survival in TCGA cohort (p =
0.036). A multivariate analysis was further performed to demonstrate that the
eight-probe panel association with poor outcome in early-stage LUAD patients
remained significant even after adjusting for different clinical variables
including staging parameters (hazard ratio, 2.03; p = 0.039). CONCLUSIONS: We
established a proof-of-concept prognostic panel consisting of eight-probe
signature to predict survival of early-stage LUAD patients of Asian and Caucasian
populations.
PMID- 27484809
TI - Meeting Report and Special Issue Preface: The 54th Seminar of the Korean Society
of Gastrointestinal Endoscopy.
PMID- 27484808
TI - Molecularly Imprinted Intelligent Scaffolds for Tissue Engineering Applications.
AB - The development of molecularly imprinted polymers (MIPs) using biocompatible
production methods enables the possibility to further exploit this technology for
biomedical applications. Tissue engineering (TE) approaches use the knowledge of
the wound healing process to design scaffolds capable of modulating cell behavior
and promote tissue regeneration. Biomacromolecules bear great interest for TE,
together with the established recognition of the extracellular matrix, as an
important source of signals to cells, both promoting cell-cell and cell-matrix
interactions during the healing process. This review focuses on exploring the
potential of protein molecular imprinting to create bioactive scaffolds with
molecular recognition for TE applications based on the most recent approaches in
the field of molecular imprinting of macromolecules. Considerations regarding
essential components of molecular imprinting technology will be addressed for TE
purposes. Molecular imprinting of biocompatible hydrogels, namely based on
natural polymers, is also reviewed here. Hydrogel scaffolds with molecular memory
show great promise for regenerative therapies. The first molecular imprinting
studies analyzing cell adhesion report promising results with potential
applications for cell culture systems, or biomaterials for implantation with the
capability for cell recruitment by selectively adsorbing desired molecules.
PMID- 27484807
TI - Therapeutic effects of human gingiva-derived mesenchymal stromal cells on murine
contact hypersensitivity via prostaglandin E2-EP3 signaling.
AB - BACKGROUND: The immunomodulatory and anti-inflammatory functions of human gingiva
derived mesenchymal stromal cells (GMSCs) have been demonstrated in contact
hypersensitivity (CHS) models; however, their therapeutic effect during the late
phase of CHS has been poor. METHODS: The murine CHS model was induced by applying
oxazolone to the ears of mice. Mesenchymal stromal cells were applied via two
methods (intravenous or local injection) at three time points: 1 day before
sensitization, 1 day before challenge, or 1 h after challenge. Prostaglandin E2
(PGE2) and sulprostone were administered subcutaneously 1 h after challenge.
RESULTS: The application of GMSCs, bone marrow mesenchymal stem cells, and
adipose-derived stem cells all effectively suppressed CHS; however, GMSC
treatment exhibited the greatest efficacy. Local injection of GMSCs led to a more
marked attenuation of CHS compared with intravenous injection, especially during
the late phase of CHS, and this manifested as decreased infiltration of
inflammatory cells, suppression of the levels of various proinflammatory
cytokines, reconstruction of the disrupted Th1/Th2 balance, and upregulation of
regulatory T cells in the allergen contact areas. Pretreatment with indomethacin
significantly abrogated the GMSC-mediated immunosuppressive effects, while PGE2
application reversed the effects of indomethacin pretreatment of GMSCs. Moreover,
GMSC administration promoted the expression of EP3, a prostaglandin E receptor,
and the application of sulprostone, an agonist of EP3, significantly attenuated
CHS to a similar degree as that of GMSC administration. CONCLUSIONS: GMSCs have
reproducible and powerful immunomodulatory functions. Local injection of GMSCs is
the superior mode for therapeutic application. PGE2-EP3 signaling plays an
important role in the immunomodulatory functions of GMSCs in murine CHS.
PMID- 27484810
TI - How to Improve the Quality of Screening Endoscopy in Korea: National Endoscopy
Quality Improvement Program.
AB - In Korea, gastric cancer screening, either esophagogastroduodenoscopy or upper
gastrointestinal series (UGIS), is performed biennially for adults aged 40 years
or older. Screening endoscopy has been shown to be associated with localized
cancer detection and better than UGIS. However, the diagnostic sensitivity of
detecting cancer is not satisfactory. The National Endoscopy Quality Improvement
(QI) program was initiated in 2009 to enhance the quality of medical institutions
and improve the effectiveness of the National Cancer Screening Program (NCSP).
The Korean Society of Gastrointestinal Endoscopy developed quality standards
through a broad systematic review of other endoscopic quality guidelines and
discussions with experts. The standards comprise five domains: qualifications of
endoscopists, endoscopic unit facilities and equipment, endoscopic procedure,
endoscopy outcomes, and endoscopic reprocessing. After 5 years of the QI program,
feedback surveys showed that the perception of QI and endoscopic practice
improved substantially in all domains of quality, but the quality standards need
to be revised. How to avoid missing cancer in endoscopic procedures in daily
practice was reviewed, which can be applied to the mass screening endoscopy. To
improve the quality and effectiveness of NCSP, key performance indicators,
acceptable quality standards, regular audit, and appropriate reimbursement are
necessary.
PMID- 27484811
TI - Predictors of Inadequate Bowel Preparation and Salvage Options on Colonoscopy.
AB - Inadequate bowel preparation is observed in more than 25% of all colonoscopies.
Identification of predictive factors for inadequate colon cleaning is helpful and
more detailed preparation methods should be used for patients at high risk. Age,
male sex, inpatient status, and comorbidities were identified as independent risk
factors in several previous studies. In patients with insufficient colon
preparation, colon irrigation with endoscopic pumps or next-day colonoscopy
following further bowel cleaning should be performed. In order to improve the
efficacy and safety of both bowel preparation and colonoscopy, the endoscopic
team should identify the patient's medical conditions and choose the optimal
bowel preparation agent and regimen.
PMID- 27484812
TI - Optimal Colonoscopy Surveillance Interval after Polypectomy.
AB - The detection and removal of adenomatous polyps and postpolypectomy surveillance
are considered important for the control of colorectal cancer (CRC). Surveillance
using colonoscopy is an effective tool for preventing CRC after colorectal
polypectomy, especially if compliance is good. In current practice, the intervals
between colonoscopies after polypectomy are variable. Different recommendations
for recognizing at risk groups and defining surveillance intervals after an
initial finding of colorectal adenomas have been published. However, high-grade
dysplasia and the number and size of adenomas are known major cancer predictors.
Based on this, a subgroup of patients that may benefit from intensive
surveillance colonoscopy can be identified.
PMID- 27484813
TI - Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease.
AB - Patients with inflammatory bowel disease have significantly increased in recent
decades in Korea. Intestinal tuberculosis (ITB) and intestinal Behcet's disease
(BD), which should be differentiated from Crohn's disease (CD), are more frequent
in Korea than in the West. Thus, the accurate diagnosis of these inflammatory
diseases is problematic in Korea and clinicians should fully understand their
clinical and endoscopic characteristics. Ulcerative colitis mostly presents with
rectal inflammation and continuous lesions, while CD presents with discontinuous
inflammatory lesions and frequently involves the ileocecal area. Involvement of
fewer than four segments, a patulous ileocecal valve, transverse ulcers, and
scars or pseudopolyps are more frequently seen in ITB than in CD. A few ulcers
with discrete margins are a typical endoscopic finding of intestinal BD. However,
the differential diagnosis is difficult in many clinical situations because
typical endoscopic findings are not always observed. Therefore, clinicians should
also consider symptoms and laboratory, pathological, and radiological findings,
in addition to endoscopic findings.
PMID- 27484814
TI - Recent Advanced Endoscopic Management of Endoscopic Retrograde
Cholangiopancreatography Related Duodenal Perforations.
AB - The management strategy for endoscopic retrograde cholangiopancreatography
related duodenal perforation can be determined based on the site and extent of
injury, the patient's condition, and time to diagnosis. Most cases of
perivaterian or bile duct perforation can be managed with a biliary stent or
nasobiliary drainage. Duodenal wall perforations had been treated with immediate
surgical repair. However, with the development of endoscopic devices and
techniques, endoscopic closure has been reported to be a safe and effective
treatment that uses through-the-scope clips, ligation band, fibrin glue,
endoclips and endoloops, an over-the-scope clipping device, suturing devices,
covering luminal stents, and open-pore film drainage. Endoscopic therapy could be
instituted in selected patients in whom perforation was identified early or
during the procedure. Early diagnosis, proper conservative management, and
effective endoscopic closure are required for favorable outcomes of non-surgical
management. If endoscopic treatment fails, or in the cases of clinical
deterioration, prompt surgical management should be considered.
PMID- 27484816
TI - Three-dimensional analysis of marginal and internal fit of copings fabricated
with polyetherketoneketone (PEKK) and zirconia.
AB - PURPOSE: The purpose of this in vitro study was to compare and analyze the three
dimensional marginal and internal fit of PEKK and zirconia copings. METHODS: Two
acrylic models of the right maxillary canine, first molar were fabricated as
master dies and duplicated by one-step dual viscosity impressions. Five stone
replicas from each model were digitized with a blue-light scanner and copings
were machined from Pekkton and Zirconia blanks. The inner surface of all the
copings and two original acrylic models were digitized by a highly accurate
optical scanner. By superimposing the digitized coping data with the CAD
reference die three-dimensionally, visual fit-discrepancies were drawn by
calculating the root mean square (RMS) and visualized on a color-difference map.
Each calculated RMS-value was statistically analyzed by 3-way ANOVA. In addition,
Student's t-test was conducted in order to verify the significance (alpha=.05) of
fit-discrepancies based on the type of abutment tooth and the materials. RESULTS:
Mean RMS-values for marginal fit (internal fit) ranged from 51.64+/-1.5 (36.12+/
1.34) to 69.62+/-8.11 (41.6+/-1.63)MUm. Differences in marginal fit (canine:
P=.001; molar: P=.047) and internal fit (canine: P=.017; molar: P=.046) were
statistically significant. The results of the 3-way ANOVA showed statistically
significant differences in the RMS values of the two groups for the material
(P<.001), the types of the abutment tooth (P<.001), and the measured region
(P<.001). CONCLUSIONS: The marginal and internal fit of both PEKK and zirconia
copings of both canine and molar were within the clinically acceptable range.
However, the PEKK presented better fitness compared with the zirconia.
PMID- 27484815
TI - Primary immunodeficiency associated with chromosomal aberration - an ESID survey.
AB - BACKGROUND: Patients with syndromic features frequently suffer from recurrent
respiratory infections, but little is known about the spectrum of immunological
abnormalities associated with their underlying chromosomal aberrations outside
the well-known examples of Down and DiGeorge syndromes. Therefore, we performed
this retrospective, observational survey study. METHODS: All members of the
European Society for Immunodeficiencies (ESID) were invited to participate by
reporting their patients with chromosomal aberration (excluding Down and DiGeorge
syndromes) in combination with one or more identified immunological abnormalities
potentially relating to primary immunodeficiency. An online questionnaire was
used to collect the patient data. RESULTS: Forty-six patients were included from
16 centers (24 males, 22 females; median age 10.4 years [range 1.0-69.2 years];
36 pediatric, 10 adult patients). A variety of chromosomal aberrations associated
with immunological abnormalities potentially relating to primary immune
deficiency was reported. The most important clinical presentation prompting the
immunological evaluation was 'recurrent ear-nose-throat (ENT) and airway
infections'. Immunoglobulin isotype and/or IgG-subclass deficiencies were the
most prevalent immunological abnormalities reported. CONCLUSIONS: Our survey
yielded a wide variety of chromosomal aberrations associated with immunological
abnormalities potentially relating to primary immunodeficiency. Although
respiratory tract infections can often also be ascribed to other causes (e.g.
aspiration or structural abnormalities), we show that a significant proportion of
patients also have an antibody deficiency requiring specific treatment (e.g.
immunoglobulin replacement, antibiotic prophylaxis). Therefore, it is important
to perform immunological investigations in patients with chromosomal aberrations
and recurrent ENT or airway infections, to identify potential immunodeficiency
that can be specifically treated.
PMID- 27484817
TI - CIP2A regulates proliferation and apoptosis of multiple myeloma cells.
AB - Multiple myeloma (MM) is one of the most common causes of mortality from
hematological malignancy in China. Recent studies have demonstrated that
cancerous inhibitor of protein phosphatase 2A (CIP2A) may exhibit a role in
promoting the growth of cancer; however, the function of CIP2A in MM remains
unknown. In the present study, the expression and molecular mechanism underlying
the effects of CIP2A in patients with MM and in MM cell lines were elucidated.
Firstly, the expression of CIP2A was detected in patients with MM and in MM cell
lines by reverse transcription-quantitative polymerase chain reaction.
Furthermore, silencing of CIP2A with short hairpin RNA was performed in MM cells,
and the impact on the proliferation and apoptosis of RPMI-8226 cells was analyzed
(as endogenous CIP2A is highly expressed in RPMI-8226 cell lines compared with
other cells). CIP2A was significantly elevated in patients with MM and in MM cell
lines, and silencing of CIP2A could inhibit the proliferation ability of RPMI
8226 cells in vitro. In addition, CIP2A knockdown induced apoptosis and led to
substantial reduction of c-Myc protein levels in MM cell lines. This study
suggested that CIP2A inhibition may provide a promising therapeutic strategy for
patients with MM.
PMID- 27484818
TI - First molecular detection and characterization of Sarcocystis species in
slaughtered cattle in North-West Tunisia.
AB - Sarcocystis spp. is one of the most prevalent foodborne parasites infecting both
animals and humans. Consumption of raw or undercooked infected meat is a risk
factor of human intestinal sarcocystosis. The present study aimed to estimate the
prevalence of Sarcocystis species infecting slaughtered Tunisian cattle in North
West Tunisia (Beja governorate). DNA was extracted from 150 beef meat samples and
a PCR-restriction fragment length polymorphism was used for identification. The
overall infection prevalence of Sarcocystis spp. was 38% (57/150). Two species
were identified, namely S. hominis (25%; 39/150) and S. cruzi (12%; 18/150). For
both species, the highest prevalence was in Thibar locality (52.9 and 17.6% for
S. hominis and S. cruzi, respectively). The molecular prevalence of S. cruzi was
significantly higher in animals aged between two and eight years (19.2%; 10/52).
This is the first molecular identification of Sarcocystis species in Tunisian
cattle. Further studies in both human and animal Tunisian populations are needed
to rank this parasitic disease among others.
PMID- 27484819
TI - Eutrophication, Ammonia Intoxication, and Infectious Diseases: Interdisciplinary
Factors of Mass Mortalities in Cultured Nile Tilapia.
AB - The present study was designed to assess the possible causes of the mass
mortalities of Nile Tilapia Oreochromis niloticus at El-Behera Governorate,
Egypt, in relationship to environmental and microbiotic factors. Water samples
were collected from fish farms at different locations and from Lake Edku to
analyze water temperature, water pH, salinity, biological oxygen demand,
dissolved oxygen, total ammonia nitrogen, and un-ionized ammonia. A number of
moribund and freshly dead fish were sampled and submitted to our laboratory for
microbiological, molecular, and histopathological examination. Water analysis of
the fish farms revealed noticeable increases in the previously mentioned
physicochemical parameters. Clinical examinations of moribund fish showed severe
gill rot and massive external and internal hemorrhages. Ordinary and molecular
laboratory findings confirmed the presence of Branchiomyces sp. in gill tissue
and mixed bacterial fish pathogens (Streptococcus agalactiae, Vibrio
alginolyticus, V. parahaemolyticus, Pseudomonas anguilliseptica, and P.
aeruginosa) in visceral organs. The histopathological and transmission electron
microscopic examinations revealed severe necrosis of gill filaments and blockage
of branchial blood vessels and lamellar capillaries with Branchiomyces sp. hyphae
and spores mixed with different shapes of bacteria. Severe inflammations were
detected in liver, kidney, heart, and brain tissues. Ultimately, we can conclude
that the syndrome of mass fish kills in this area is a consequence of ecological
damage to the aquatic environment, which is mainly related to natural and
anthropogenic factors, as well as to the presence of infectious agents. Received
September 30, 2015; accepted April 12, 2016.
PMID- 27484820
TI - Factors associated with diagnostic stage of hip osteoarthritis due to acetabular
dysplasia among Japanese female patients: a cross-sectional study.
AB - BACKGROUND: In Japan, the majority of hip osteoarthritis (OA) was caused by
acetabular dysplasia, and about 90 % of patients were female. The present study
focused on Japanese female patients with hip OA due to acetabular dysplasia, and
examined the associated factors with OA staging at diagnosis, in special
reference to body weight. METHODS: Study subjects were 336 Japanese women who
were newly diagnosed with hip OA caused by acetabular dysplasia at 15 hospitals
in 2008. The self-administered questionnaire elicited patients' body weight at
age 20 and at OA diagnosis. Four ranked OA staging according to radiographic
findings of the hip joint (pre-OA, initial stage, advanced stage or terminal
stage) was regarded as the outcome index. Proportional odds models in logistic
regression were used to calculate odds ratios (ORs) and 95 % confidence intervals
(CIs) for severer stage of OA. RESULTS: At diagnosis, 45 % of patients suffered
from terminal stage of OA, whereas 13 % and 14 % were categorized into pre-OA and
initial stage, respectively. After adjustment for potential confounders, weight
gain since age 20 revealed the increased ORs for severer OA stage at diagnosis
(OR 2.02; 95 % CI, 1.07-3.80). Other significant characteristics were age (67+
vs. 20-49 years, OR 12.4), lower education (junior high school vs. junior college
or higher, OR 4.00), parity (OR 2.19), lower acetabular head index (<60.0 vs.
71.1+, OR 2.36), and longer duration since symptom onset (6.0+ vs. <1.0 year, OR
2.94). CONCLUSIONS: Weight gain since age 20 might be involved in mechanisms of
OA development, which is independent of age or severity of acetabular dysplasia.
PMID- 27484821
TI - Patient Education for Consumer-Mediated HIE. A Pilot Randomized Controlled Trial
of the Department of Veterans Affairs Blue Button.
AB - OBJECTIVES: Consumer-mediated health information exchange (HIE) is one of the
three types of HIE designated by the Office of the National Coordinator. HIE is
intended to improve the quality of care while reducing cost, yet empirical
support for this claim is mixed. Future research should identify the contexts
whereby HIE is most effective. METHODS: This study was conducted as a pilot two
arm randomized controlled trial. In the intervention arm, 27 veterans were taught
how to generate a Continuity of Care Document (CCD) within the Blue Button
feature of their VA patient portal and were then asked to share it with their
community non-VA provider. In the attention control condition, 25 Veterans were
taught how to look up health information on the Internet. The impact of this
training on the next non-VA medical visit was examined. RESULTS: Nineteen (90%)
veterans in the intervention arm shared their CCD with their non-VA provider as
compared with 2 (17%) in the attention control arm (p<0.001). Both veterans and
non-VA providers indicated high satisfaction with the CCD. Comparison of medical
records between the VA and non-VA providers did not indicate improved medication
reconciliation (p=0.72). If veterans shared their CCD prior to their non-VA
providers ordering laboratory tests, the number of duplicate laboratories was
significantly reduced (p=0.02). CONCLUSIONS: In this pilot randomized controlled
trial, training 52 veterans to share their CCD was feasible and accepted by both
patients and providers. Sharing this document appeared to reduce duplicate
laboratory draws, but did not have an impact on documented medication list
concordance.
PMID- 27484822
TI - Estimating Marginal Healthcare Costs Using Genetic Variants as Instrumental
Variables: Mendelian Randomization in Economic Evaluation.
AB - Accurate measurement of the marginal healthcare costs associated with different
diseases and health conditions is important, especially for increasingly
prevalent conditions such as obesity. However, existing observational study
designs cannot identify the causal impact of disease on healthcare costs. This
paper explores the possibilities for causal inference offered by Mendelian
randomization, a form of instrumental variable analysis that uses genetic
variation as a proxy for modifiable risk exposures, to estimate the effect of
health conditions on cost. Well-conducted genome-wide association studies provide
robust evidence of the associations of genetic variants with health conditions or
disease risk factors. The subsequent causal effects of these health conditions on
cost can be estimated using genetic variants as instruments for the health
conditions. This is because the approximately random allocation of genotypes at
conception means that many genetic variants are orthogonal to observable and
unobservable confounders. Datasets with linked genotypic and resource use
information obtained from electronic medical records or from routinely collected
administrative data are now becoming available and will facilitate this form of
analysis. We describe some of the methodological issues that arise in this type
of analysis, which we illustrate by considering how Mendelian randomization could
be used to estimate the causal impact of obesity, a complex trait, on healthcare
costs. We describe some of the data sources that could be used for this type of
analysis. We conclude by considering the challenges and opportunities offered by
Mendelian randomization for economic evaluation.
PMID- 27484823
TI - Service evaluation of an educational intervention to improve sexual health
services in primary care implemented using a step-wedge design: analysis of
chlamydia testing and diagnosis rate changes.
AB - BACKGROUND: Providing sexual health services in primary care is an essential step
towards universal provision. However they are not offered consistently. We
conducted a national pilot of an educational intervention to improve staff's
skills and confidence to increase chlamydia testing rates and provide condoms
with contraceptive information plus HIV testing according to national guidelines,
known as 3Cs&HIV. The effectiveness of the pilot on chlamydia testing and
diagnosis rates in general practice was evaluated. METHODS: The pilot was
implemented using a step-wedge design over three phases during 2013 and 2014 in
England. The intervention combined educational workshops with posters, testing
performance feedback and continuous support. Chlamydia testing and diagnosis
rates in participating general practices during the control and intervention
periods were compared adjusting for seasonal trends in chlamydia testing and
differences in practice size. Intervention effect modification was assessed for
the following general practice characteristics: chlamydia testing rate compared
to national median, number of general practice staff employed, payment for
chlamydia screening, practice urban/rurality classification, and proximity to
sexual health clinics. RESULTS: The 460 participating practices conducted 26,021
tests in the control period and 18,797 tests during the intervention period.
Intention-to-treat analysis showed no change in the unadjusted median tests and
diagnoses per month per practice after receiving training: 2.7 vs 2.7; 0.1 vs
0.1. Multivariable negative binomial regression analysis found no significant
change in overall testing or diagnoses post-intervention (incidence rate ratio
(IRR) 1.01, 95 % confidence interval (CI) 0.96-1.07, P = 0.72; 0.98 CI 0.84-1.15,
P = 0.84, respectively). Stratified analysis showed testing increased
significantly in practices where payments were in place prior to the intervention
(IRR 2.12 CI 1.41-3.18, P < 0.001) and in practices with 6-15 staff (6-10 GPs IRR
1.35 (1.07-1.71), P = 0.012; 11-15 GPs IRR 1.37 (1.09-1.73), P = 0.007).
CONCLUSION: This national pilot of short educational training sessions found no
overall effect on chlamydia testing in primary care. However, in certain sub
groups chlamydia testing rates increased due to the intervention. This
demonstrates the importance of piloting and evaluating any service improvement
intervention to assess the impact before widespread implementation, and the need
for detailed understanding of local services in order to select effective
interventions.
PMID- 27484824
TI - Patient and physician views of accompanied consultations in occupational health.
AB - Background: Accompanied (triadic) consultations, or consultations where a third
person is present, are poorly researched and little research has been carried out
in an occupational health (OH) setting. Aims: To elicit the views of patients and
OH physicians about accompanied consultations. Methods: OH receptionists gave a
self-administered questionnaire to patients after they attended OH consultations
with a companion. We interviewed participating OH physicians to ascertain their
views on accompanied consultations. Results: Twenty-six patient questionnaires
were completed (response rate 52%). Seventy-three per cent (19) of responders
were accompanied by a spouse and 12% (3) by non-family members. Patients reported
their companion was helpful with recall of information (100%), supportive (100%),
provided extra information to the physician (81%) and enabled them to discuss the
outcome afterwards (92%). In two consultations, the companion attended to provide
support on procedural matters. Patients were not concerned that the consultation
might involve sensitive discussion or physical examination. OH physicians
reported concerns that the companion would make the consultation more difficult
or influence its outcome. They felt that written information, guidelines and
training in how to manage accompanied consultations would be useful. Conclusions:
Patients who attended OH consultations with a companion felt the companion was
beneficial to the consultation and did not have concerns about personal issues.
OH physicians felt that further guidance and training on accompanied
consultations would be useful. Written information could usefully be provided to
patients attending an OH consultation with a companion.
PMID- 27484825
TI - [Robot-assisted minimally invasive esophagectomy. German version].
AB - Esophagolymphadenectomy is the cornerstone of multimodality treatment for
resectable esophageal cancer. The preferred surgical approach is transthoracic,
with a two-field lymph node dissection and gastric conduit reconstruction. A
minimally invasive approach has been shown to reduce postoperative complications
and increase quality of life. Robot-assisted minimally invasive esophagectomy
(RAMIE) was developed to facilitate this complex thoracoscopic procedure. RAMIE
has been shown to be safe with good oncologic results and reduced morbidity. The
use of RAMIE opens new indications for curative surgery in patients with T4b
tumors, high mediastinal tumors, and lymph node metastases after neoadjuvant
treatment.
PMID- 27484826
TI - [Infections of the spine : Therapeutic strategies].
AB - Spinal infections are relatively rare entities but the incidence is significantly
increasing due to the rapidly growing numbers of interventions on the spine.
Primary infections of intervertebral discs (spondylodiscitis) and vertebral
bodies (spondylitis) are distinguished from secondary postinterventional
infections. Treatment relies primarily on either conservative or surgical
management. In the absence of indications for surgery, a conservative approach is
indicated when the patient is neurologically intact and the bony destruction is
minimal. Conservative therapeutic options are based on the microbiological
diagnosis and use of antibiotics, immobilization, analgesics and orthotics.
Indications for a surgical intervention are the presence of neurological
deficits, intraspinal abscesses, extensive osseous destruction and failure of
conservative management. Surgical therapy focusses on the decompression of neural
structures, debridement and eradication of the focus of infection, pathogen
identification, correction of the deformity and restoration of a physiological
spinal profile. Following a postoperative infection a timely diagnosis including
assessment of the extent of infection is crucial. In the case of a purely
superficial infection, antibiotic prophylaxis and close monitoring is indicated.
If findings are pronounced surgical revision, debridement together with
antibiotic therapy and if necessary vacuum-assisted closure as well as revision
ranging from exchange of implants to complete removal of osteosynthetic material
are required. Spinal infections are severe conditions frequently with residual
long-term sequelae, whether the patients are managed conservatively or
surgically.
PMID- 27484829
TI - [Lower right abdominal pain in a young woman : An ordinary appendicitis].
PMID- 27484827
TI - [Treatment of periprosthetic infections].
AB - The increasing number of prosthesis implantations and higher life expectancy lead
to a growing number of periprosthetic infections (PPI). Optimal therapy
necessitates interdisciplinary coordination of surgical and antimicrobial
treatment. Challenges in the treatment are the increased occurrence of resistant
pathogens, selection of adequate antimicrobial and surgical treatment strategies,
inappropriate pretreatment and comorbidities of patients. Current treatment
concepts lead to a high success rate in terms of infection eradication, when
correctly applied. The individual expectations and underlying conditions of each
patient must be considered when determining the therapy concept. The first step
is to distinguish between acute and chronic infections. In acute infections the
prosthesis can be retained but chronic infections necessitate a complete exchange
of the prosthesis. Complicating factors, such as compromising soft tissue and
bone conditions, osteomyelitis and infections caused by difficult-to-treat
bacteria should, however, always be treated by a complete exchange of the
prosthesis, even for acute infections. The antimicrobial treatment must be
tailored to the causative agent, the surgical strategy as well as comorbidities
and drug intolerances of the patient. It is important to distinguish between
biofilm-active eradication therapy with rifampicin for gram-positive pathogens
and quinolones for gram-negative organisms and suppression therapy. This article
gives a structured presentation of the therapy algorithm.
PMID- 27484828
TI - [Promoting Young Talents in Trauma Surgery through Students-On-Call].
AB - BACKGROUND: Due to restrictions on admission to medical school, changing claims
to an optimized work-life balance and occupational perspectives, surgical
professions in particular are struggling with strategies to motivate young
academics. Surgical disziplines aim towards a profound transfer of knowledge and
pique student's interest by ensuring a sustainable education at university.
OBJECTIVES: The goal of this study was to evaluate a Students-On-Call System
(SOCS) and to identify a financial benefit. MATERIALS AND METHODS: In this study
the SOCS was compared pre-/postevaluation using questionnaires and the supporting
X-rays within a curricular teaching module of orthopedic trauma surgery, with
students in the fourth semester of specialism and those in the practical semester
at medical school. RESULTS: The students of SOCS showed significantly better
results prior to the course and afterwards than the two other groups. By
establishing SOCS medical students get involved into the treatment of emergency
patients in the trauma resuscitation unit (TRU) and operating room (OR). Students
get the chance to enhance their comprehension of diagnostics, therapy and
decision making in surgical context. This highly valuable traineeship combines a
minimized teaching effort with an effective motivation of young academcis for the
surgical profession. A SOCS has reduced the workload of medical colleagues.
Establishing SOCS spare the residents being on call and results in reduced costs
of 23,659.86 Euro per year. CONCLUSION: The results presented show that the SOCS
leads to an excellent cost-benefit balance, which has been established in
multiple surgical departments at the medical school of the University of
Gottingen. Apart from practice-oriented surgical teaching, the SOCS is a way of
promoting successful young talent saving resources in the medical on-call
services.
PMID- 27484830
TI - A Multidimensional Diversity-Oriented Synthesis Strategy for Structurally Diverse
and Complex Macrocycles.
AB - Synthetic macrocycles are an attractive area in drug discovery. However, their
use has been hindered by a lack of versatile platforms for the generation of
structurally (and thus shape) diverse macrocycle libraries. Herein, we describe a
new concept in library synthesis, termed multidimensional diversity-oriented
synthesis, and its application towards macrocycles. This enabled the step
efficient generation of a library of 45 novel, structurally diverse, and highly
functionalized macrocycles based around a broad range of scaffolds and
incorporating a wide variety of biologically relevant structural motifs. The
synthesis strategy exploited the diverse reactivity of aza-ylides and imines, and
featured eight different macrocyclization methods, two of which were novel.
Computational analyses reveal a broad coverage of molecular shape space by the
library and provides insight into how the various diversity-generating steps of
the synthesis strategy impact on molecular shape.
PMID- 27484831
TI - Hybrid external fixation in the treatment of tibial pilon fractures: A
retrospective analysis of 162 fractures.
AB - OBJECTIVES: To determine the efficacy of hybrid external fixation in the
treatment of tibial pilon fractures. DESIGN: Retrospective, multicentre study.
PATIENTS/PARTICIPANTS: Adult patients with tibial pilon fractures treated with
hybrid external fixation. INTERVENTION: Fracture reduction with ligamentotaxis
and fixation with XCaliber hybrid external fixator. MAIN OUTCOME MEASUREMENTS:
Fracture union, complications, functional outcome (Mazur Ankle Score). RESULTS:
Union was obtained in 159 fractures at an average of 125days; there were three
delayed unions and three non-unions. The most frequent complication was
superficial pin-track infections (48), all of which responded to local wound care
and antibiotics. There were no deep infections and no DVT. Only one fracture had
loss of reduction that required frame revision. The overall functional scores
were 91 (excellent) for AO/OTA type A fractures, 89 (good) for type B fractures,
and 75 (satisfactory) for type C fractures. CONCLUSIONS: Hybrid external fixation
is an effective method of stabilising tibial pilon fractures, particularly those
with marked comminution. The minimally-invasive technique and stable fixation
enable early mobilisation, with good functional results and minimal
complications. LEVEL OF EVIDENCE: Level IV Case series.
PMID- 27484832
TI - Two new sesquiterpenoids produced by halophilic Nocardiopsis chromatogenes YIM
90109.
AB - Two new germacradiene-type sesquiterpenoids, including 1(10)E,5E-germacradiene
9beta,11-diol (or 9beta-hydroxyl germacradienol) (1) and 11-hydroxy-1(10)E,5E
germacradien-2-one (2-oxygermacradienol) (2), together with a known geosmin-type
sesquiterpenoid (1beta,4beta,4abeta,7alpha,8aalpha)-4,8a
dimethyloctahydronaphthalene-1,4a,7(2H)-triol (3), were elucidated by their NMR
spectroscopic data, HR-ESI-MS and single-crystal X-ray diffraction from the
halophilic strain Nocardiopsis chromatogenes YIM 90109. The antimicrobial
activities were evaluated by paper diffusion method.
PMID- 27484833
TI - Divergent Annexin A1 expression in periphery and gut is associated with systemic
immune activation and impaired gut immune response during SIV infection.
AB - HIV-1 disease progression is paradoxically characterized by systemic chronic
immune activation and gut mucosal immune dysfunction, which is not fully defined.
Annexin A1 (ANXA1), an inflammation modulator, is a potential link between
systemic inflammation and gut immune dysfunction during the simian
immunodeficiency virus (SIV) infection. Gene expression of ANXA1 and cytokines
were assessed in therapy-naive rhesus macaques during early and chronic stages of
SIV infection and compared with SIV-negative controls. ANXA1 expression was
suppressed in the gut but systemically increased during early infection.
Conversely, ANXA1 expression increased in both compartments during chronic
infection. ANXA1 expression in peripheral blood was positively correlated with
HLA-DR+CD4+ and CD8+ T-cell frequencies, and negatively associated with the
expression of pro-inflammatory cytokines and CCR5. In contrast, the gut mucosa
presented an anergic cytokine profile in relation to ANXA1 expression. In vitro
stimulations with ANXA1 peptide resulted in decreased inflammatory response in
PBMC but increased activation of gut lymphocytes. Our findings suggest that ANXA1
signaling is dysfunctional in SIV infection, and may contribute to chronic
inflammation in periphery and with immune dysfunction in the gut mucosa. Thus,
ANXA1 signaling may be a novel therapeutic target for the resolution of immune
dysfunction in HIV infection.
PMID- 27484834
TI - Spontaneous temperature-sensitive Pluronic((r)) based niosomes: Triggered drug
release using mild hyperthermia.
AB - Inclusion of lipids or polymers with a transition temperature closer to
physiological body temperature (40-42 degrees C) is a strategy used in tumor
therapy for more than 30 years, because it allows induction of drug release from
delivery systems by mild hyperthermia. Unfortunately, most of these thermo
sensitive carriers are removed from circulation before completion of their
function. Thus, novel multi-functional niosomes possessing spontaneous stealth
and thermo-sensitive properties were developed from L64 Pluronic((r)) and L64ox
as its derivative, in presence or absence of cholesterol. The use of L64 both as
amphiphilic constituent and thermo-sensitive molecule, gave the possibility to
bypass the use of additional excipients and increased the system
biocompatibility. Niosomes diameter ranged from 400 to 750nm and were long term
stable. Calcein and 5-FU possess great affinity to niosomal matrices rich in PEO
groups. Negative Z-potential values were attributed to the negative charges onto
the niosomes surface and generally change according to the temperature. The in
vitro drugs release studies were performed at 25 degrees C, 37 degrees C and 42
degrees C, that are representative of certain conditions (storage, physiological
condition and mild hyperthermia, respectively). Results showed that L64-based
niosomes possess spontaneous thermo-sensitive properties: drugs releases were
found to be more pronounced at 42 degrees C. These early results are a promising
first step for the development of multi-functional devices that combine several
advantages such as stealth properties and temperature controllability at the
desired location and time, for a more specific and efficient pharmacological
therapy.
PMID- 27484835
TI - Tumor microenvironment-responsive micelles for pinpointed intracellular release
of doxorubicin and enhanced anti-cancer efficiency.
AB - Internal stimuli, such as intracellular lysosomal pH, enzyme, redox and
reduction, can be applied to improve biological specificity of chemotherapeutic
drugs for cancer therapy. Thus, functionalized copolymers based on their response
to specific microenvironment of tumor regions have been designed as smart drug
vesicles for enhanced anti-cancer efficiency and reduced side effects. Herein, we
reported dually pH/reduction-responsive novel micelles based on self-assembly of
carboxymethyl chitosan-cysteamine-N-acetyl histidine (CMCH-SS-NA) and doxorubicin
(DOX). The tailor-made dually responsive micelles demonstrated favorable
stability in normal physiological environment and triggered rapid drug release in
acidic and/or reduction environment. Additionally, the nanocarriers responded to
the intracellular environment in an ultra-fast manner within several minutes,
which led to the pinpointed release of DOX in tumor cells effectively and ensured
higher DOX concentrations within tumor areas with the aid of targeted delivery,
thereby leading to enhanced tumor ablation. Thus, this approach with sharp drug
release behavior represented a versatile strategy to provide a promising paradigm
for cancer therapy.
PMID- 27484836
TI - Angiopep2-functionalized polymersomes for targeted doxorubicin delivery to
glioblastoma cells.
AB - A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on
polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS
PMOXA) diblock copolymers was developed to evaluate their potential to actively
target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated
to the surface of preformed Ps to target the low density lipoprotein receptor
related protein 1 that are overexpressed in blood brain barrier (BBB) and glioma
cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%.
The angiopep2-functionalized Ps showed no cellular toxicity after 24h and
enhanced the cellular uptake around 5 times more in U87MG glioblastoma cells
compared to the non-targeted Ps. The encapsulation efficiency of doxorubicin
(DOX) in Ps was 13% by co-solvent method, compared to a film rehydration method
(4%). The release profiles of the DOX from Ps showed a release of 42% at pH 5.5
and 40% at pH 7.4 after 24h, indicating that Ps can efficiently retain the DOX
with a slow release rate. Furthermore, the in vitro antiproliferative activity of
DOX-loaded Ps-Angiopep2 showed enhanced toxicity to U87MG glioblastoma cells,
compared to non-targeted Ps. Overall, our in vitro results suggested that
angiopep2-conjugated Ps can be used as nanocarriers for efficient targeted DOX
delivery to glioblastoma cells.
PMID- 27484837
TI - Mutations in the TMCO3 Gene are Associated with Cornea Guttata and Anterior Polar
Cataract.
AB - The molecular basis for cornea guttata and anterior polar cataract remains
idiopathic in most cases. In this study, our aim was to identify the disease
associated gene in Chinese patients with these conditions. Patients with the
conditions from two Chinese families, and ten sporadic patients, were
investigated. Genome-wide linkage and exome sequencing analyses showed
transmembrane and coiled-coil domain 3 (TMCO3) as the disease candidate gene for
a coding heterozygous mutation c.41C > T, resulting in a P14L amino acid change
that co-segregated with the disease phenotype as discovered in Family A. TMCO3
belongs to the monovalent cation: protein antiporter 2 transporter family, a
moderately large group whose members all share a very similar function under
normal physiological conditions. The gene is expressed in the human cornea, lens
capsule, and choroid-retinal pigment epithelium. This study reveals, for the
first time, that mutations in TMCO3 are associated with cornea guttata and
anterior polar cataract, warranting further investigation into the pathogenesis
of this disorder.
PMID- 27484838
TI - IGFBP5 enhances osteogenic differentiation potential of periodontal ligament stem
cells and Wharton's jelly umbilical cord stem cells, via the JNK and MEK/Erk
signalling pathways.
AB - OBJECTIVES: Mesenchymal stem cell (MSC)-mediated tissue regeneration represents a
promising strategy for repair of tissue defects, but its molecular mechanisms
remain unclear, restricting the use of MSCs. Our previous study indicated that
insulin-like growth factor-binding protein 5 (IGFBP5) exerted a valuable effect
on osteogenic differentiation of MSCs, but its molecular mechanisms underlying
directed differentiation remained unclear. In this study, we have investigated
the molecular role of IGFBP5 in regulating this osteogenic differentiation
potential. MATERIALS AND METHODS: Periodontal ligament stem cells (PDLSCs) were
isolated from periodontal ligament tissue. Wharton's jelly of umbilical cord stem
cells (WJCMSCs) was obtained commercially. Lentiviral IGFBP5 shRNA was used to
silence IGFBP5. Retroviruses expressing wild-type IGFBP5 were used to overexpress
IGFBP5 in the WJCMSCs. Recombinant human IGFBP5 protein (rhIGFBP5) was used to
treat PDLSCs for 24 h. Western blot analysis was used to detect the MAPK
signalling pathway, and alkaline phosphatase (ALP) activity, Alizarin Red
staining and quantitative calcium analysis were used to study osteogenic
differentiation potentials. RESULTS: Overexpression of IGFBP5 or rhIGFBP5
increased expression levels of phosphorylated c-Jun N-terminal kinase (p-JNK),
phosphorylated mitogen-activated protein kinase 1 and 2 (p-MEK1/2) and
phosphorylated extracellular regulated protein kinases (p-Erk1/2) in both WJCMSCs
and PDLSCs. Consistently, silenced IGFBP5 was found to effectively inhibit
expression of p-JNK, p-Erk1/2 and p-MEK1/2 in PDLSCs and WJCMSCs. Furthermore,
inhibition of JNK by its inhibitor, SP600125, or MEK/Erk signalling by its
inhibitor, PD98059, dramatically blocked IGFBP5-enhanced ALP activity and in
vitro mineralization in both PDLSCs and WJCMSCs. CONCLUSIONS: Our results
demonstrated that IGFBP5 promoted osteogenic differentiation potentials of PDLSCs
and WJCMSCs via the JNK and MEK/Erk signalling pathways.
PMID- 27484839
TI - A Validation Study of the Need for Affect Questionnaire-Short Form in Legal
Contexts.
AB - We evaluated the psychometric properties of scores on the Need for Affect-Short
Form (NAQ-S) in 3 samples: undergraduate students (Sample I), jury-eligible
community members (Sample II), and forensic clinicians (Sample III). Concerning
factor structure, the NAQ-S 2-factor structure displayed good fit to the data in
Sample I, with mostly acceptable levels of internal consistency for both approach
and avoidance scores. Construct validity patterns were observed such that
approach scores were most strongly correlated with female gender and trait
agreeableness scores, whereas avoidance scores were most strongly correlated to
trait agreeableness scores. Criterion validity associations emerged in that
approach scores displayed main effects on mock juror judgments in hate crimes,
and forensic clinician judgments of violence risk estimation. Finally, avoidance
scores displayed moderating effects on recommended sentencing length by hate
crime victim type. Implications are discussed for emotion in legal decision
making and future research.
PMID- 27484841
TI - PCR methodology and applications for the detection of human fungal pathogens.
AB - INTRODUCTION: Polymerase chain reaction (PCR) has emerged as a promising
technology for the rapid and reliable detection and identification of medical
mycoses. Recent technological advancements - including microarray, multiplex PCR
with magnetic resonance, and beacon probes - have mitigated the technical
difficulties of performing nucleic amplification in fungi, thereby improving the
sensitivity and specificity of PCR-based assays. In this paper, we examine
current applications of PCR in the diagnosis of human fungal infections and look
ahead to emerging techniques that may play a larger role in molecular diagnostics
in the future. AREAS COVERED: This review includes a brief overview of the
advantages and disadvantages of PCR using various clinical specimens, manual
versus automated DNA extraction procedures, panfungal versus specific targets,
and spectrum of pathogens detected. This is followed by a brief synopsis of
species-specific PCR approaches and a more in-depth look at the obstacles to
widespread implementation. Expert commentary: The review concludes with a short
perspective for the next five years, including the hurdles to standardization and
validation, as well as the role of PCR coupled with electrospray-ionization mass
spectrometry (PCR/ESI-MS) or nuclear magnetic resonance for the diagnosis of
medical mycoses.
PMID- 27484840
TI - MRF4 negatively regulates adult skeletal muscle growth by repressing MEF2
activity.
AB - The myogenic regulatory factor MRF4 is highly expressed in adult skeletal muscle
but its function is unknown. Here we show that Mrf4 knockdown in adult muscle
induces hypertrophy and prevents denervation-induced atrophy. This effect is
accompanied by increased protein synthesis and widespread activation of muscle
specific genes, many of which are targets of MEF2 transcription factors. MEF2
dependent genes represent the top-ranking gene set enriched after Mrf4 RNAi and a
MEF2 reporter is inhibited by co-transfected MRF4 and activated by Mrf4 RNAi. The
Mrf4 RNAi-dependent increase in fibre size is prevented by dominant negative
MEF2, while constitutively active MEF2 is able to induce myofibre hypertrophy.
The nuclear localization of the MEF2 corepressor HDAC4 is impaired by Mrf4
knockdown, suggesting that MRF4 acts by stabilizing a repressor complex that
controls MEF2 activity. These findings open new perspectives in the search for
therapeutic targets to prevent muscle wasting, in particular sarcopenia and
cachexia.
PMID- 27484842
TI - Cytotoxicity of methanol extracts of 10 Cameroonian medicinal plants towards
multi-factorial drug-resistant cancer cell lines.
AB - BACKGROUND: Cancer chemotherapy is still hampered by clinical failures due to
multi-drug resistance (MDR) of tumor cells. In the present study, we have
investigated the cytotoxicity of 20 methanol extracts from 10 medicinal plants
against the sensitive leukemia CCRF-CEM cells. The most cytotoxic extracts were
then further tested on a panel of 8 human cancer cell lines, including various
MDR phenotypes. METHODS: The cytotoxicity of the 20 methanol extracts from 10
Cameroonian medicinal plants was determined using a resazurin reduction assay.
Meanwhile, flow cytometry was used to measure cell cycle, apoptosis,
mitochondrial membrane potential (MMP), and reactive oxygen species (ROS).
RESULTS: In the preliminary assay using CCRF-CEM cells, 12 extracts from five
plants displayed IC50 values below 80 MUg/mL, namely Albizia adianthifolia,
Alchornea cordifolia, Alchornea laxiflora, Pennisetum purpureum, and Spathodea
campanulata. the four best extracts were from two plants: Albizia adianthifolia
roots (AAR) and bark (AAB) as well as Alchornea cordifolia leaves (ACL) and bark
(ACB) had respective IC50 values of 0.98 MUg/mL, 1.45 MUg/mL, 8.02 MUg/mL and
12.57 MUg/mL in CCRF-CEM cells. They were further tested in 8 other cell lines as
well as in normal AML12 hepatocytes. IC50 values ranging from 2.71 MUg/mL
(towards glioblastoma U87MG.DeltaEGFR cells) to 10.30 MUg/mL (towards breast
adenocarcinoma MDA-MB-231-BCRP cells) for AAB, from 3.43 MUg/mL (towards U87MG
cells) to 10.77 MUg/mL (towards colon carcinoma HCT116 (p53 (-/-) ) cells) for
AAR and from 0.11 MUg/mL (towards CCRF-CEM cells) to 108 MUg/mL (towards leukemia
CEM/ADR5000 cells) for doxorubicin (as control drug) were obtained. ACL and ACB
extracts displayed selective activities. AAR and ACL extracts induced apoptosis
in CCRF-CEM cells, through caspases activation and loss of MMP, while apoptotic
cell death was mediated by MMP diruption and increase ROS production for ACL.
CONCLUSION: Some of the tested plants namely Albizia adianthifolia, Alchornea
cordifolia, Alchornea laxiflora, Pennisetum purpureum, Spathodea campanulata
represent a potential source of novel anticancer drugs. Especially, Albizia
adianthifolia and Alchornea cordifolia revealed considerable cytotoxic activities
that could be exploited to develop phytomedicines to fight cancers including MDR
phenotypes.
PMID- 27484844
TI - Differential abundance of muscle proteome in cultured channel catfish (Ictalurus
punctatus) subjected to ante-mortem stressors and its impact on fillet quality.
AB - The effects of environmental and handling stress during catfish (Ictalurus
punctatus) aquaculture were evaluated to identify the biochemical alterations
they induce in the muscle proteome and their impacts on fillet quality.
Temperature (25 degrees C and 33 degrees C) and oxygen (~2.5mg/L [L] and >5mg/L
[H]) were manipulated followed by sequential socking (S) and transport (T) stress
to evaluate changes in quality when fish were subjected to handling (25-H-ST;
temperature-oxygen-handling), oxygen stress (25-L-ST), temperature stress (33-H
ST) and severe stress (33-L-ST). Instrumental color and texture of fillets were
evaluated, and muscle proteome profile was analyzed. Fillet redness, yellowness
and chroma decreased, and hue angle increased in all treatments except
temperature stress (33-H-ST). Alterations in texture compared to controls were
observed when oxygen levels were held high. In general, changes in the abundance
of structural proteins and those involved in protein regulation and energy
metabolism were identified. Rearing under hypoxic conditions demonstrated a shift
in metabolism to ketogenic pathways and a suppression of the stress-induced
changes as the severity of the stress increased. Increased proteolytic activity
observed through the down-regulation of various structural proteins could be
responsible for the alterations in color and texture.
PMID- 27484843
TI - Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0
Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi
institutional Series.
AB - BACKGROUND: Three prospective randomised trials reported discordant findings
regarding the impact of adjuvant radiation therapy (aRT) versus observation for
metastasis-free survival (MFS) and overall survival (OS) among patients with
pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these
trials systematically included patients who underwent early salvage radiation
therapy (esRT). OBJECTIVE: To test the hypothesis that aRT was associated with
better cancer control and survival compared with observation followed by esRT.
DESIGN, SETTING, AND PARTICIPANTS: Using a multi-institutional cohort from seven
tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with
undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009.
Patients were stratified into two groups: aRT (group 1) versus observation
followed by esRT in case of PSA relapse (group 2). Specifically, esRT was
administered at a PSA level <=0.5ng/ml. INTERVENTION: We compared aRT versus
observation followed by esRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The
evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested
the association between groups (aRT vs observation followed by esRT) and
oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or
higher), pathologic Gleason score (<=6, 7, or >=8), surgical margin status
(negative vs positive), and year of surgery. An interaction with groups and
baseline patient risk was tested for the hypothesis that the impact of aRT versus
observation followed by esRT was different by pathologic characteristics. The
nonparametric curve fitting method was used to explore graphically the
relationship between MFS and OS at 8 yr and baseline patient risk (derived from
the multivariable analysis). RESULTS AND LIMITATIONS: Overall, 243 patients (48%)
underwent aRT, and 267 (52%) underwent initial observation. Within the latter
group, 141 patients experienced PSA relapse and received esRT. Median follow-up
after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136),
respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr
after surgery were not significantly different between the two groups. These
results were confirmed in multivariable analysis, in which observation followed
by esRT was not associated with a significantly higher risk of distant metastasis
(hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared
with aRT. Using the nonparametric curve fitting method, a comparable proportion
of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer
features (p=0.9 and p=0.7, respectively). Limitations consisted of the
retrospective nature of the study and the relatively small size of the patient
population. CONCLUSIONS: At long-term follow-up, no significant differences
between aRT and esRT were observed for MFS and OS. Our study, although based on
retrospective data, suggests that esRT does not compromise cancer control and
potentially reduces overtreatment associated with aRT. PATIENT SUMMARY: At long
term follow-up, no significant differences in terms of distant metastasis and
mortality were observed between immediate postoperative adjuvant radiation
therapy (aRT) and initial observation followed by early salvage radiation therapy
(esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT
does not compromise cancer control and potentially reduces overtreatment
associated with aRT.
PMID- 27484845
TI - Production and characterization of spray-dried theophylline powders prepared from
fresh milk for potential use in paediatrics.
AB - OBJECTIVE: This work evaluates the potential of using fresh milk to deliver
theophylline to children. METHODS: Theophylline-fresh milk systems were prepared
using different solids ratios (0 : 1-1 : 0) and three fat contents in commercial
milks (low, medium and high), which were spray-dried at different inlet air
temperatures (Tinlet - 105, 130 and 150 degrees C). The process was evaluated
for yield and the resulting powders for moisture content (MC), particle size and
shape, density and wettability. Theophylline-milk potential interactions
(differential scanning calorimetry (DSC) and FT-IR) and chemical (theophylline
content) and microbiological stability of powders (shelf and in-use) were also
evaluated. KEY FINDINGS: The production yield (13.6-76.0%), MC (0.0-10.3%) and
contact angles in water (77.29-93.51 degrees ) were significantly (P < 0.05)
affected by Tinlet , but no differences were found concerning the mean particle
size (3.0-4.3 MUm) of the different powders. The milk fat content significantly
(P < 0.05) impacted on the density (1.244-1.552 g/cm3 ). Theophylline content
remained stable after 6 months of storage, before extemporaneous reconstitution.
After reconstitution in water, low-fat milk samples (stored at 4 degrees C) met
the microbial pharmacopoeia criteria for up to 7 days. No theophylline-milk
components interaction was observed. CONCLUSION: Spray-dried milk-composed
powders may be used as vehicles for theophylline delivery in paediatrics
following further characterization and in-vivo evaluation.
PMID- 27484846
TI - Hairy matters: MtDNA quantity and sequence variation along and among human head
hairs.
AB - Hairs from the same donor have been found to differ in mtDNA sequence within and
among themselves and from other tissues, which impacts interpretation of results
obtained in a forensic setting. However, little is known on the magnitude of this
phenomenon and published data on systematic studies are scarce. We addressed this
issue by generating mtDNA control region (CR) profiles of >450 hair fragments
from 21 donors by Sanger-type sequencing (STS). To mirror forensic scenarios, we
compared hair haplotypes from the same donors to each other, to the corresponding
buccal swab reference haplotypes and analyzed several fragments of individual
hairs. We also investigated the effects of hair color, donor sex and age, mtDNA
haplogroup and chemical treatment on mtDNA quantity, amplification success and
variation. We observed a wide range of individual CR sequence variation. The
reference haplotype was the only or most common (>=75%) hair haplotype for most
donors. However, in two individuals, the reference haplotype was only found in
about a third of the investigated hairs, mainly due to differences at highly
variable positions. Similarly, most hairs revealed the reference haplotype along
their entire length, however, about a fifth of the hairs contained up to 71% of
segments with deviant haplotypes, independent of the longitudinal position.
Variation affected numerous positions, typically restricted to the individual
hair and in most cases heteroplasmic, but also fixed (i.e. homoplasmic)
substitutions were observed. While existing forensic mtDNA interpretation
guidelines were found still sufficient for all comparisons to reference
haplotypes, some comparisons between hairs from the same donor could yield false
exclusions when those guidelines are strictly followed. This study pinpoints the
special care required when interpreting mtDNA results from hair in forensic
casework.
PMID- 27484847
TI - Propensity score-based analysis of outcomes of laparoscopic versus open liver
resection for colorectal metastases.
AB - BACKGROUND: There is a need for high-level evidence regarding the added value of
laparoscopic (LLR) compared with open (OLR) liver resection. The aim of this
study was to compare the surgical and oncological outcomes of patients with
colorectal liver metastases (CRLM) undergoing LLR and OLR using propensity score
matching to minimize bias. METHODS: This was a single-centre retrospective study
using a prospective database of patients undergoing liver resection for CRLM
between August 2004 and April 2015. Co-variates selected for matching included:
number and size of lesions, tumour location, extent and number of resections,
phase of surgical experience, location and lymph node status of primary tumour,
perioperative chemotherapy, unilobar or bilobar disease, synchronous or
metachronous disease. Prematching and postmatching analyses were compared.
Surgical and oncological outcomes were analysed. RESULTS: Some 176 patients
undergoing LLR and 191 having OLR were enrolled. After matching, 133 patients
from each group were compared. At prematching analysis, patients in the LLR group
showed a longer overall survival (OS) and higher R0 rate than those in the OLR
group (P = 0.047 and P = 0.030 respectively). Postmatching analyses failed to
confirm these results, showing similar OS and R0 rate between the LLR and OLR
group (median OS: 55.2 versus 65.3 months respectively, hazard ratio 0.70 (95 per
cent c.i. 0.42 to 1.05; P = 0.082); R0 rate: 92.5 versus 86.5 per cent, P =
0.186). The 5-year OS rate was 62.5 (95 per cent c.i. 45.5 to 71.5) per cent) for
OLR and 64.3 (48.2 to 69.5) per cent for LLR. Longer duration of surgery, lower
blood loss and morbidity, and shorter postoperative stay were found for LLR on
postmatching analysis. CONCLUSION: Propensity score matching showed that LLR for
CRLM may provide R0 resection rates and long-term OS comparable to those for OLR,
with lower blood loss and morbidity, and shorter postoperative hospital stay.
PMID- 27484849
TI - Tin nanoparticles as an effective conductive additive in silicon anodes.
AB - We have found that the addition of tin nanoparticles to a silicon-based anode
provides dramatic improvements in performance in terms of both charge capacity
and cycling stability. Using a simple procedure and off-the-shelf additives and
precursors, we developed a structure in which the tin nanoparticles are
segregated at the interface between the silicon-containing active layer and the
solid electrolyte interface. Even a minor addition of tin, as small as ~2% by
weight, results in a significant decrease in the anode resistance, as confirmed
by electrochemical impedance spectroscopy. This leads to a decrease in charge
transfer resistance, which prevents the formation of electrically inactive "dead
spots" in the anode structure and enables the effective participation of silicon
in the lithiation reaction.
PMID- 27484848
TI - Multiple sclerosis: clinical profiling and data collection as prerequisite for
personalized medicine approach.
AB - Multiple sclerosis (MS) is a highly heterogeneous disease as it can present inter
individually as well as intra-individually, with different disease phenotypes
emerging during different stages in the long-term disease course. In addition to
advanced immunological, genetic and magnetic resonance imaging (MRI) profiling of
the patient, the clinical profiling of MS patients needs to be widely implemented
in clinical practice and improved by including a greater range of relevant
parameters as patient-reported outcomes. It is crucial to implement a high
standard of clinical characterization of individual patients as this is key to
effective long-term observation and evaluation.To generate reliable real-world
data, individual clinical data should be collected in specific MS registries
and/or using intelligent software instruments as the Multiple Sclerosis
Documentation System 3D. Computational analysis of biological processes will play
a key role in the transition to personalized MS treatment. Major breakthroughs in
the areas of bioinformatics and computational systems biology will be required to
process this complex information to enable improved personalization of treatment
for MS patients.
PMID- 27484850
TI - Optogenetic and chemogenetic strategies for sustained inhibition of pain.
AB - Spatially targeted, genetically-specific strategies for sustained inhibition of
nociceptors may help transform pain science and clinical management. Previous
optogenetic strategies to inhibit pain have required constant illumination, and
chemogenetic approaches in the periphery have not been shown to inhibit pain.
Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be
used to persistently inhibit pain for long periods of time through infrequent
transdermally delivered light pulses, reducing required light exposure by >98%
and resolving a long-standing limitation in optogenetic inhibition. We
demonstrate that the viral expression of the hM4D receptor in small-diameter
primary afferent nociceptor enables chemogenetic inhibition of mechanical and
thermal nociception thresholds. Finally, we develop optoPAIN, an optogenetic
platform to non-invasively assess changes in pain sensitivity, and use this
technique to examine pharmacological and chemogenetic inhibition of pain.
PMID- 27484851
TI - Clinicopathological feature and prognosis of primary hepatic gastrointestinal
stromal tumor.
AB - Compared to gastric gastrointestinal stromal tumor (GIST), hepatic GIST is very
rare in clinic. Reports on clinicopathological feature and prognosis of this rare
disease are limited in literature. The purpose of this study was, therefore, to
summarize clinical and pathological features as well as prognosis of the primary
hepatic GIST. One case of primary hepatic GIST from our center and 22 cases
reported in MEDLINE or China National Knowledge Infrastructure (CNKI) were
enrolled into this study. Clinicopathological features as well as survival data
of hepatic GIST were analyzed and compared with 297 gastric GISTs and 59 small
intestinal GISTs from our center. Majority of the 22 cases (95.7%) of hepatic
GIST was larger than 5 cm in size, and 75.0% of the tumors were over 5/50 HPF in
mitotic index. Most of the hepatic GISTs (85.7%) displayed spindle cell shape in
morphology. All of the hepatic GIST (100%) enrolled in this study were classified
as high-risk category by the National Institute of Health (NIH) risk
classification. The 5-year median disease-free survival (DFS) time was 24.0
months and 5-year disease-specific survival (DSS) rate was 33.3%, respectively.
Distribution of clinicopathological features was significantly different among
hepatic, gastric, and small intestinal GIST. The DFS and DSS of hepatic GIST were
significantly lower than those of the other two groups. Majority of the hepatic
GIST is large in size and highly malignant. Prognosis of the primary hepatic GIST
is worse than that of gastric GIST and small intestinal GIST.
PMID- 27484853
TI - Evidence for a functional role of calsequestrin 2 in mouse atrium.
AB - AIM: Several genetically modified mice models were studied so far to investigate
the role of cardiac calsequestrin (CSQ2) for the contractile function of the
ventricle and for the occurrence of ventricular tachycardia. Using a CSQ2
knockout mouse, we wanted to study also the atrial function of CSQ2. METHODS: The
influence of CSQ2 on atrial function and, for comparison, ventricular function
was studied in isolated cardiac preparations and by echocardiography as well as
electrocardiography in mice with deletion of CSQ2. RESULTS: Using deletion of
exon 1, we have successfully generated a constitutive knockout mouse of the
calsequestrin 2 gene (CSQ2-/- ). CSQ2 protein was absent in the heart (atrium,
ventricle), but also in oesophagus and skeletal muscle of homozygous knockout
mice. In 6-month-old CSQ2-/- mice, relative left atrial weight was increased,
whereas relative heart weight was unchanged. The staircase phenomena in paced
left atrial preparations on force of contraction and the post-rest potentiation
were different between wild type and CSQ2-/- indicative for a decreased
sarcoplasmic Ca2+ load and supporting an important role of CSQ2 also in the
atrium. The incidence of arrhythmias was increased in CSQ2-/- . In 2-year-old
CSQ2-/- mice, cardiac hypertrophy and heart failure were noted possibly as a
result of chronically increased cytosolic Ca2+ levels. CONCLUSION: These data
suggest a functional role of CSQ2 not only in the ventricle but also in the
atrium of mammalian hearts. Loss of CSQ2 function can cause not only arrhythmias,
but also cardiac hypertrophy and heart failure.
PMID- 27484852
TI - KIF1A mediates axonal transport of BACE1 and identification of independently
moving cargoes in living SCG neurons.
AB - Neurons rely heavily on axonal transport to deliver materials from the sites of
synthesis to the axon terminals over distances that can be many centimetres long.
KIF1A is the neuron-specific kinesin with the fastest reported anterograde motor
activity. Previous studies have shown that KIF1A transports a subset of synaptic
proteins, neurofilaments and dense-core vesicles. Using two-colour live imaging,
we showed that beta-secretase 1 (BACE1)-mCherry moves together with KIF1A-GFP in
both the anterograde and retrograde directions in superior cervical ganglions
(SCG) neurons. We confirmed that KIF1A is functionally required for BACE1
transport by using KIF1A siRNA and a KIF1A mutant construct (KIF1A-T312M) to
impair its motor activity. We further identified several cargoes that have little
or no co-migration with KIF1A-GFP and also move independently from BACE1-mCherry.
Together, these findings support a primary role for KIF1A in the anterograde
transport of BACE1 and suggest that axonally transported cargoes are sorted into
different classes of carrier vesicles in the cell body and are transported by
cargo-specific motor proteins through the axon.
PMID- 27484854
TI - Neural architecture of the "transient" ON directionally selective (class IIb1)
ganglion cells in rabbit retina, partly co-stratified with starburst amacrine
cells.
AB - Recent physiological studies coupled with intracellular staining have subdivided
ON directionally selective (DS) ganglion cells of rabbit retina into two types.
One exhibits more "transient" and more "brisk" responses (ON DS-t), and the other
has more "sustained' and more "sluggish" responses (ON DS-s), although both
represent the same three preferred directions and show preference for low
stimulus velocity, as reported in previous studies of ON DS ganglion cells in
rabbit retina. ON DS-s cells have the morphology of ganglion cells previously
shown to project to the medial terminal nucleus (MTN) of the accessory optic
system, and the MTN-projecting, class IVus1 cells have been well-characterized
previously in terms of their dendritic morphology, branching pattern, and
stratification. ON DS-t ganglion cells have a distinctly different morphology and
exhibit heterotypic coupling to amacrine cells, including axon-bearing amacrine
cells, with accompanying synchronous firing, while ON DS-s cells are not coupled.
The present study shows that ON DS-t cells are morphologically identical to the
previously well-characterized, "orphan" class IIb1 ganglion cell, previously
regarded as a member of the "brisk-concentric" category of ganglion cells. Its
branching pattern, quantitatively analyzed, is similar to that of the
morphological counterparts of X and Y cells, and very different from that of the
ON DS-s ganglion cell. Close analysis of the dendritic stratification of class
IIb1 ganglion cells together with fiducial cells indicates that they differ from
that of the ON DS-s cells. In agreement with one of the three previous studies,
class IIb1/ON DS-t cells, unlike class IVus1/ON DS-s ganglion cells, in the main
do not co-stratify with starburst amacrine cells. As the present study shows,
however, portions of their dendrites do deviate from the main substratum, coming
within range of starburst boutons. Parsimony favors DS input from starburst
amacrine cells both to ON DS-s and to ON DS-t ganglion cells, given the
similarity of their DS responses, but further studies will be required to
substantiate the origin of the DS responses of ON DS-t cells. Previously reported
OFF DS responses in ON DS-t cells, unmasked by pharmacological agents, and
mediated by gap junctions with amacrine cells, suggests an unusual trans
sublaminar organization of directional selectivity in the inner plexiform layer,
connecting sublamina a and sublamina b.
PMID- 27484855
TI - High frequency of vertebral fracture and low bone quality in patients with
rheumatoid arthritis-Results from TOMORROW study.
AB - OBJECTIVES: Osteoporosis is one of the complications in patients with rheumatoid
arthritis (RA). In this study, we researched the morbidity of existing vertebral
fractures and the risk factors for vertebral fractures in patients with RA.
METHODS: This study included 413 participants, 208 patients with RA, and 205 age-
and sex-matched controls without RA. Clinical data, radiographic assessment of
vertebral fracture from T4 to L4 in thoracic and lumber spine, bone mineral
density (BMD), and bone metabolic markers (BMM) were analyzed. RESULTS: Vertebral
fractures were observed more frequently, severe and multiple in patients with RA.
In the logistic regression analysis, age (adjusted odds ratios (OR): 1.07, 95%
confidence interval (CI): 1.04-1.09) and RA (adjusted OR: 1.72, 95% CI: 1.04
2.83) were risk factors for existing vertebral fracture. Moreover, two bone
matrix-related markers, undercarboxylated osteocalcin (ucOC) (adjusted OR: 1.68,
95% CI: 1.02-2.78), and urinary pentocidine (adjusted OR: 2.51, 95% CI: 1.48
4.24) were associated with existing vertebral fracture. CONCLUSIONS: High
frequent, multiple, and severe vertebral fractures were found in patients with RA
compared to the controls. Low bone quality might be the cause of the frequent
prevalence of vertebral fracture in patients with RA.
PMID- 27484856
TI - The biplanar open wedge high tibial osteotomy preserving the tibial tubercle.
AB - BACKGROUND: High tibial osteotomy (HTO) is a treatment option for relatively
young patients with isolated medial compartment arthritis of the knee. Medial
open wedge osteotomies allow easier control of correction, but can lead to
patella infera as a result of distalization of the tibial tubercle. This
retrospective study reports results of a biplanar tibial tubercle preserving HTO,
designed to preserve patellar height. METHODS: The study is a retrospective
analysis of 12 consecutive patients (11 men, 1 woman) average age 39.6 years who
underwent the procedure between 2009 and 2012. A biplanar open wedge tibial
osteotomy was performed and stabilised with a medial locking plate. Patients were
allowed full weight bearing at 6 weeks. Preoperative and postoperative function
was recorded on the Oxford knee score, Lysholm score and Tegner activity scale.
Minimum follow up was 26 months. RESULTS: All patients had healing of the
osteotomy with no delayed union. Eleven patients reported improvement in symptoms
with an average preoperative Oxford score of 26 and postoperative score of 39 out
of 48. The Lysholm score improved from 58 to 72 out of 100. There was one point
improvement in Tegner activity scale. There was no statistical difference in
patellar height before and one year after surgery. The correction in varus
averaged 8.3 degrees . CONCLUSION: The biplanar High tibial Osteotomy allows
preservation of patellar height, while achieving desired varus correction.
PMID- 27484858
TI - Enduring sleep complaints predict health problems: a six-year follow-up of the
survey of health and retirement in Europe.
AB - OBJECTIVES: Sleep complaints are common and enduring among old people. The study
aimed to extend current knowledge by exploring the effects of episodic versus
chronic sleep complaints on a range of physical and mental health outcomes.
METHODS: Older adults (N = 8934, mean age = 64) who participated in Waves 1, 2
and 4 of the Survey of Health, Ageing and Retirement in Europe (SHARE) reported
sleep and health outcome measures. Episodic sleep complaints, in the first or in
the second wave and chronic sleep complaints, in both waves were recorded.
Outcomes in Wave 4 included physical symptoms, difficulties in activities of
daily living and low quality of life. RESULTS: Logistic regressions examined
whether episodic and chronic sleep complaints at W1 and W2 predict W4 health
outcomes. Chronic sleep complaints predicted worse outcomes, compared to no sleep
difficulties and to episodic sleep complaints, even after adjusting for
demographic characteristics and previous levels of health. CONCLUSION: Sleep
complaints and mainly chronic sleep complaints are related to elevated risk of
future health and functional problems. Caregivers are encouraged to address sleep
complaints and provide their older patients with help before sleep complaints
become persistent.
PMID- 27484859
TI - Online Determination of Graphene Lattice Orientation Through Lateral Forces.
AB - Rapid progress in graphene engineering has called for a simple and effective
method to determine the lattice orientation on graphene before tailoring graphene
to the desired edge structures and shapes. In this work, a wavelet transform
based frequency identification method is developed to distinguish the lattice
orientation of graphene. The lattice orientation is determined through the
different distribution of the frequency power spectrum just from a single scan
line. This method is proven both theoretically and experimentally to be useful
and controllable. The results at the atomic scale show that the frequencies vary
with the lattice orientation of graphene. Thus, an adjusted angle to the desired
lattice orientation (zigzag or armchair) can easily be calculated based on the
frequency obtained from the single scan line. Ultimately, these results will play
a critical role in wafer-size graphene engineering and in the manufacturing of
graphene-based nanodevices.
PMID- 27484860
TI - Influence of Thickness on the Electrical Transport Properties of Exfoliated
Bi2Te3 Ultrathin Films.
AB - In this work, the mechanical exfoliation method has been utilized to fabricate
Bi2Te3 ultrathin films. The thickness of the ultrathin films is revealed to be
several tens of nanometers. Weak antilocalization effects and Shubnikov de Haas
oscillations have been observed in the magneto-transport measurements on
individual films with different thickness, and the two-dimensional surface
conduction plays a dominant role. The Fermi level is found to be 81 meV above the
Dirac point, and the carrier mobility can reach ~6030 cm(2)/(Vs) for the 10-nm
film. When the film thickness decreases from 30 to 10 nm, the Fermi level will
move 8 meV far from the bulk valence band. The coefficient alpha in the Hikami
Larkin-Nagaoka equation is shown to be ~0.5, manifesting that only the bottom
surface of the Bi2Te3 ultrathin films takes part in transport conductions. These
will pave the way for understanding thoroughly the surface transport properties
of topological insulators.
PMID- 27484857
TI - Finding their way: themes in germ cell migration.
AB - Embryonic germ cell migration is a vital component of the germline lifecycle. The
translocation of germ cells from the place of origin to the developing somatic
gonad involves several processes including passive movements with underlying
tissues, transepithelial migration, cell adhesion dynamics, the establishment of
environmental guidance cues and the ability to sustain directed migration. How
germ cells accomplish these feats in established model organisms will be
discussed in this review, with a focus on recent discoveries and themes conserved
across species.
PMID- 27484861
TI - Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of
Therapeutics for Niemann-Pick Disease Type A.
AB - : : Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by
mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency
in ASM function results in lysosomal accumulation of sphingomyelin and
neurodegeneration. Currently, there is no effective treatment for NPA. To
accelerate drug discovery for treatment of NPA, we generated induced pluripotent
stem cells from two patient dermal fibroblast lines and differentiated them into
neural stem cells. The NPA neural stem cells exhibit a disease phenotype of
lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this
disease model, we also evaluated three compounds that reportedly reduced
lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme
replacement therapy with ASM. We found that alpha-tocopherol, delta-tocopherol,
hydroxypropyl-beta-cyclodextrin, and ASM reduced sphingomyelin accumulation and
enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells
possess the characteristic NPA disease phenotype that can be ameliorated by
tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of
cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate
that the NPA neural stem cells can be used as a new cell-based disease model for
further study of disease pathophysiology and for high-throughput screening to
identify new lead compounds for drug development. SIGNIFICANCE: Currently, there
is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate
drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were
generated from patient dermal fibroblasts and differentiated into neural stem
cells. By using the differentiated NPA neuronal cells as a cell-based disease
model system, alpha-tocopherol, delta-tocopherol, and hydroxypropyl-beta
cyclodextrin significantly reduced sphingomyelin accumulation in these NPA
neuronal cells. Therefore, this cell-based NPA model can be used for further
study of disease pathophysiology and for high-throughput screening of compound
libraries to identify lead compounds for drug development.
PMID- 27484869
TI - Linking cognitive and visual perceptual decline in healthy aging: The information
degradation hypothesis.
AB - Several hypotheses attempt to explain the relation between cognitive and
perceptual decline in aging (e.g., common-cause, sensory deprivation, cognitive
load on perception, information degradation). Unfortunately, the majority of past
studies examining this association have used correlational analyses, not allowing
for these hypotheses to be tested sufficiently. This correlational issue is
especially relevant for the information degradation hypothesis, which states that
degraded perceptual signal inputs, resulting from either age-related
neurobiological processes (e.g., retinal degeneration) or experimental
manipulations (e.g., reduced visual contrast), lead to errors in perceptual
processing, which in turn may affect non-perceptual, higher-order cognitive
processes. Even though the majority of studies examining the relation between age
related cognitive and perceptual decline have been correlational, we reviewed
several studies demonstrating that visual manipulations affect both younger and
older adults' cognitive performance, supporting the information degradation
hypothesis and contradicting implications of other hypotheses (e.g., common
cause, sensory deprivation, cognitive load on perception). The reviewed evidence
indicates the necessity to further examine the information degradation hypothesis
in order to identify mechanisms underlying age-related cognitive decline.
PMID- 27484870
TI - Devices for visually impaired people: High technological devices with low user
acceptance and no adaptability for children.
AB - Considering that cortical plasticity is maximal in the child, why are the
majority of technological devices available for visually impaired users meant for
adults and not for children? Moreover, despite high technological advancements in
recent years, why is there still no full user acceptance of existing sensory
substitution devices? The goal of this review is to create a link between
neuroscientists and engineers by opening a discussion about the direction that
the development of technological devices for visually impaired people is taking.
Firstly, we review works on spatial and social skills in children with visual
impairments, showing that lack of vision is associated with other sensory and
motor delays. Secondly, we present some of the technological solutions developed
to date for visually impaired people. Doing this, we highlight the core features
of these systems and discuss their limits. We also discuss the possible reasons
behind the low adaptability in children.
PMID- 27484871
TI - Commentary on the special issue "The Adolescent Brain": How can we run operant
paradigms in a preclinical adolescent model? Technical tips and future
perspectives.
PMID- 27484868
TI - Consequences of adolescent use of alcohol and other drugs: Studies using rodent
models.
AB - Studies using animal models of adolescent exposure to alcohol, nicotine,
cannabinoids, and the stimulants cocaine, 3,4-methylenedioxymethampethamine and
methamphetamine have revealed a variety of persisting neural and behavioral
consequences. Affected brain regions often include mesolimbic and prefrontal
regions undergoing notable ontogenetic change during adolescence, although it is
unclear whether this represents areas of specific vulnerability or particular
scrutiny to date. Persisting alterations in forebrain systems critical for
modulating reward, socioemotional processing and cognition have emerged,
including apparent induction of a hyper-dopaminergic state with some drugs and/or
attenuations in neurons expressing cholinergic markers. Disruptions in cognitive
functions such as working memory, alterations in affect including increases in
social anxiety, and mixed evidence for increases in later drug self
administration has also been reported. When consequences of adolescent and adult
exposure were compared, adolescents were generally found to be more vulnerable to
alcohol, nicotine, and cannabinoids, but generally not to stimulants. More work
is needed to determine how adolescent drug exposure influences sculpting of the
adolescent brain, and provide approaches to prevent/reverse these effects.
PMID- 27484872
TI - Affordance processing in segregated parieto-frontal dorsal stream sub-pathways.
AB - The concept of affordances indicates "action possibilities" as characterized by
object properties the environment provides to interacting organisms. Affordances
relate to both perception and action and refer to sensory-motor processes
emerging from goal-directed object interaction. In contrast to stable properties,
affordances may vary with environmental context. A sub-classification into stable
and variable affordances was proposed in the framework of the ROSSI project
(Borghi et al., 2010; Borghi and Riggio, 2015, 2009). Here, we present a
coordinate-based meta-analysis of functional imaging studies on object
interaction targeting consistent anatomical correlates of these different types
of affordances. Our review revealed the existence of two parallel (but to some
extent overlapping) functional pathways. The network for stable affordances
consists of predominantly left inferior parietal and frontal cortices in the
ventro-dorsal stream, whereas the network for variable affordances is localized
preferentially in the dorso-dorsal stream. This is in line with the proposal of
differentiated affordances: stable affordances are characterized by the knowledge
of invariant object features, whereas variable affordances underlie adaptation to
changing object properties.
PMID- 27484873
TI - Structural evolution and strength change of a metallic glass at different
temperatures.
AB - The structural evolution of a Zr64.13Cu15.75Ni10.12Al10 metallic glass is
investigated in-situ by high-energy synchrotron X-ray radiation upon heating up
to crystallization. The structural rearrangements on the atomic scale during the
heating process are analysed as a function of temperature, focusing on shift of
the peaks of the structure factor in reciprocal space and the pair distribution
function and radial distribution function in real space which are correlated with
atomic rearrangements and progressing nanocrystallization. Thermal expansion and
contraction of the coordination shells is measured and correlated with the bulk
coefficient of thermal expansion. The characteristics of the microstructure and
the yield strength of the metallic glass at high temperature are discussed aiming
to elucidate the correlation between the atomic arrangement and the mechanical
properties.
PMID- 27484874
TI - A robust preference for cheap-and-easy strategies over reliable strategies when
verifying personal memories.
AB - People depend on various sources of information when trying to verify their
autobiographical memories. Yet recent research shows that people prefer to use
cheap-and-easy verification strategies, even when these strategies are not
reliable. We examined the robustness of this cheap strategy bias, with scenarios
designed to encourage greater emphasis on source reliability. In three
experiments, subjects described real (Experiments 1 and 2) or hypothetical
(Experiment 3) autobiographical events, and proposed strategies they might use to
verify their memories of those events. Subjects also rated the reliability, cost,
and the likelihood that they would use each strategy. In line with previous work,
we found that the preference for cheap information held when people described how
they would verify childhood or recent memories (Experiment 1), personally
important or trivial memories (Experiment 2), and even when the consequences of
relying on incorrect information could be significant (Experiment 3). Taken
together, our findings fit with an account of source monitoring in which the
tendency to trust one's own autobiographical memories can discourage people from
systematically testing or accepting strong disconfirmatory evidence.
PMID- 27484875
TI - Total hip replacement: increasing femoral offset improves functional outcome.
AB - INTRODUCTION: The aim of this study was to assess the independent effect of
radiographic measures of implant position, relative to pre-operative anatomical
assessment, on the functional outcome of total hip arthroplasty according to
change in the Oxford hip score (OHS) 1 year post surgery. METHODS: A prospective
cohort study was preformed to assess whether improvement in functional outcome
(change in OHS at 1 year) and the relationship with femoral offset and length,
and acetabular offset and height. After a power calculation 359 patients were
recruited to the study and radiographic measures were performed by blinded
observers. Regression analysis was used to assess the independent effect of the
four radiographic measurements after adjusting for confounding variables.
RESULTS: There was a significant (p < 0.001) decrease in acetabular offset [5.3
mm, 95 % confidence interval (CI) 4.4-6.2] and increase in femoral offset (6.1
mm, 95 % CI 5.4-6.8). Hence there was no significant change in overall offset.
Femoral offset was the only radiographic measure to be achieved statistical
significance (r = 0.198, 95 % CI 0.063-0.333, p = 0.004) in relation to clinical
outcome, with increasing offset being associated with a greater improvement in
the OHS. On combining femoral and acetabular offset increasing offset was
associated with a greater improvement in the OHS (r = 0.10, 95 % CI 0.01-0.19, p
= 0.04). CONCLUSION: This study supports the long-held biomechanical theory of
medialisation of the acetabular component with compensatory increased femoral
offset results in improved functional outcome.
PMID- 27484876
TI - Graft position in arthroscopic anterior cruciate ligament reconstruction:
anteromedial versus transtibial technique.
AB - INTRODUCTION: When treating anterior cruciate ligament (ACL) injuries, the
position of the ACL graft plays a key role in regaining postoperative knee
function and physiologic kinematics. In this study, we aimed to compare graft
angle, graft position in tibial tunnel, and tibial and femoral tunnel positions
in patients operated with anteromedial (AM) and transtibial (TT) methods to those
of contralateral healthy knees. MATERIALS AND METHODS: Forty-eight patients who
underwent arthroscopic ACL reconstruction with ipsilateral hamstring tendon
autograft were included. Of these, 23 and 25 were treated by AM and TT
techniques, respectively. MRI was performed at 18.4 and 19.7 months
postoperatively in AM and TT groups. Graft angles, graft positions in the tibial
tunnel and alignment of tibial and femoral tunnels were noted and compared in
these two groups. The sagittal graft insertion tibia midpoint distance (SGON) has
been used for evaluation of graft position in tunnel. RESULTS: Sagittal ACL graft
angles in operated and healthy knees of AM patients were 57.78 degrees and 46.80
degrees (p < 0.01). With respect to TT patients, ACL graft angle was 58.87
degrees and 70.04 degrees on sagittal and frontal planes in operated knees
versus 47.38 degrees and 61.82 degrees in healthy knees (p < 0.001). ACL graft
angle was significantly different between the groups on both sagittal and frontal
planes (p < 0.001). Sagittal graft insertion tibia midpoint distance ratio was
0.51 and 0.48 % in the operated and healthy knees of AM group (p < 0.001) and
0.51 and 0.48 % in TT group (p < 0.001). Sagittal tibial tunnel midpoint distance
ratio did not differ from sagittal graft insertion tibia midpoint distance of
healthy knees in either group. Femoral tunnel clock position was better in AM
[right knee 10:19 o'clock-face position (310 degrees +/- 4 degrees ); left knee
1:40 (50 degrees +/- 3 degrees )] compared with TT group [right knee 10:48 (324
degrees +/- 5 degrees ); left knee 1:04 (32 degrees +/- 4 degrees )]. With
respect to the sagittal plane, the anterior-posterior position of femoral tunnel
was better in AM patients. Lysholm scores and range of motion of operated knees
in the AM and TT groups showed no significant difference (p > 0.05). CONCLUSIONS:
Precise reconstruction on sagittal plane cannot be obtained with either AM or TT
technique. However, AM technique is superior to TT technique in terms of
anatomical graft positioning. Posterior-placed grafts in tibial tunnel prevent
ACL reconstruction, although tibial tunnel is drilled on sagittal plane.
PMID- 27484877
TI - Association Between Any Major Discrimination and Current Cigarette Smoking Among
Adult African American Men.
AB - BACKGROUND: Findings from previous research has demonstrated a positive
relationship between interpersonal discrimination and cigarette smoking.
Cigarette smoking is proposed to be an externalizing coping mechanism used to
alleviate discrimination. At the national level, it is unclear if discrimination
is associated with cigarette smoking among African American men. OBJECTIVE: The
aim of the study was to examine the association between discrimination and
cigarette smoking among a national sample of African American men. METHODS: Using
data from the National Survey of American Life (n = 1,271), multivariable
logistic regression was used to examine the relationship between discrimination
and cigarette smoking. RESULTS: Thirty-two percent of the men were current
smokers. Controlling for everyday discrimination, major discrimination, major
stress, depressive symptoms, age, being married, household income, and education,
African American men who experienced major discrimination had a higher odd of
being a current smoking (odds ratio: 1.11, 95% confidence interval: 1.02-1.21)
than African American men who did not experience major discrimination.
Conclusion/Importance: Findings suggest that African American men may use
cigarette smoking as a mechanism to alleviate the experiences of discrimination.
Future studies should continue to examine factors associated with African
American men's smoking behavior in efforts to inform culturally relevant
interventions.
PMID- 27484879
TI - Treatment of early-stage human epidermal growth factor 2-positive cancers among
medicare enrollees: age and race strongly associated with non-use of trastuzumab.
AB - Adjuvant trastuzumab for human epidermal growth factor receptor-2 (HER2)-positive
breast cancer is highly efficacious regardless of age. Recent data suggested that
many older patients with HER2-positive disease do not receive adjuvant
trastuzumab. Nevertheless, some of this 'under-treatment' may be clinically
appropriate. We used Surveillance, Epidemiology and End Results (SEER)-Medicare
data to identify patients aged >= 66 with stage >= Ib-III, HER2-positive breast
cancer diagnosed during 2010-2011 (HER2 status available) who did not have a
history of congestive heart failure. We described all systemic treatments
received and sociodemographic and clinical characteristics associated with
treatment patterns. Among 770 women 44.4 % did not receive trastuzumab, including
21.8 % who received endocrine therapy only, 6.3 % who received chemotherapy (+/
endocrine therapy) and 16.2 % who did not receive any systemic therapy. In
addition to age and grade, race was strongly associated with non-use of
trastuzumab (64.4 % of Non-Hispanic blacks vs. 43.6 % of whites did not receive
trastuzumab, adjusted ORNon-Hispanic black vs. white = 3.14, 95 %CI = 1.38-7.17),
and many patients with stage III disease did not receive trastuzumab. Further,
16.2 % of patients did not receive any systemic treatment and this occurred more
frequently for black patients. Over 40 % of older patients with indication to
receive adjuvant trastuzumab did not receive it and nearly 20 % of these patients
did not receive any other treatment. Although treatment omission may be
appropriate in some cases, we observed concerning differences in trastuzumab
receipt, particularly for black women. Strategies to optimize care for older
patients and to eliminate treatment disparities are urgently needed.
PMID- 27484878
TI - Brainstem Monitoring in the Neurocritical Care Unit: A Rationale for Real-Time,
Automated Neurophysiological Monitoring.
AB - Patients with severe traumatic brain injury or large intracranial space-occupying
lesions (spontaneous cerebral hemorrhage, infarction, or tumor) commonly present
to the neurocritical care unit with an altered mental status. Many experience
progressive stupor and coma from mass effects and transtentorial brain herniation
compromising the ascending arousal (reticular activating) system. Yet, little
progress has been made in the practicality of bedside, noninvasive, real-time,
automated, neurophysiological brainstem, or cerebral hemispheric monitoring. In
this critical review, we discuss the ascending arousal system, brain herniation,
and shortcomings of our current management including the neurological exam,
intracranial pressure monitoring, and neuroimaging. We present a rationale for
the development of nurse-friendly-continuous, automated, and alarmed-evoked
potential monitoring, based upon the clinical and experimental literature,
advances in the prognostication of cerebral anoxia, and intraoperative
neurophysiological monitoring.
PMID- 27484880
TI - A pooled analysis of CYP2D6 genotype in breast cancer prevention trials of low
dose tamoxifen.
AB - Decreased CYP2D6 activity is associated with lower levels of active tamoxifen
metabolites. We examined the impact of CYP2D6 genotype on tamoxifen
pharmacokinetics, biomarker activity, and efficacy in a pooled analysis of low
dose tamoxifen. Four randomized breast cancer prevention trials of very-low-dose
(1 mg/day, n = 52 or 10 mg/week, n = 152) or low-dose tamoxifen (5 mg/day, n =
171) were pooled. DNA from 367 subjects was genotyped for CYP2D6 alleles
associated with absent (PM allele: *3, *4, *5, *6, *7, *8, *12, and *14), reduced
(IM allele: *9, *10, *17, *29, *41), normal (EM allele), or increased (UM: *XN)
enzyme activity. Associations of tamoxifen, metabolites, activity biomarkers, and
event-free survival with rapid (UM/EM, UM/IM, EM/EM, EM/IM, or EM/PM alleles)
versus slow metabolizers (PM/IM or PM/PM) were investigated through random
effects models, with 'study' as the random factor, and Cox regression models,
adjusting for confounders. Rapid metabolizers had higher endoxifen levels than
slow metabolizers: 15.3 versus 12.2 ng/mL (P = 0.018) with 5 mg/day, and 3.8
versus 2.8 ng/mL (P = 0.004) with 1 mg/day or 10 mg/week tamoxifen. The IGF-I
decrease correlated with endoxifen (P = 0.002) and 4-hydroxytamoxifen levels,
demonstrating steeper decreases at higher metabolite levels (P = 0.001). After a
median follow-up of 12 years, rapid metabolizers with prior history of breast
neoplasms allocated to tamoxifen 5 mg/day had a 60 % reduction of risk of
recurrences (HR = 0.40, 95 % CI: 0.16-0.99) compared to slow metabolizers. CYP2D6
genotype may have an impact on tamoxifen efficacy at low doses. Trials
investigating tamoxifen dose adjustments based on the woman's hormonal context
and CYP2D6 genotype are warranted.
PMID- 27484882
TI - New Insights into the Reliability of Automatic Dynamic Methods for Oral
Bioaccessibility Testing: A Case Study for BGS102 soil.
AB - Dynamic flow-through extraction is attracting a great deal of attention for real
time monitoring of the bioaccessible fraction of metal species in environmental
solid substrates compared to its batchwise manual counterparts. There is however
a lack of studies on the harmonization and validation of in vitro dynamic methods
for physiologically based extraction tests against in vivo bioavailability
methods. This work is aimed at evaluating the reliability of dynamic flow-through
extraction methods for estimation of oral bioaccessible fractions of Cu, Zn, Pb,
Ni, Cr, and As under worst-case extraction conditions in the gastric compartment
based on the BGS102 guidance soil using the in vivo validated Unified BARGE (UBM)
test, commonly performed under batchwise mode. Good overall agreement between
batch and dynamic UBM results was obtained for the tested elements, except for
Pb, as a consequence of the slow leaching kinetics identified with the dynamic
method and the contribution of readsorption phenomena in the course of the
gastric digestion. Metal-soil phase associations and their relationship with
gastric bioaccessible fractions were elucidated using the so-called Chemometric
Identification of Substrates and Element Distributions method based on sequential
extraction with a variety of chemicals of increasing acidity as applied to both
static and dynamic bioaccessibility data.
PMID- 27484881
TI - Higher Activities of Defense-Associated Enzymes may Contribute to Greater
Resistance of Manchurian Ash to Emerald Ash Borer Than A closely Related and
Susceptible Congener.
AB - Emerald ash borer (EAB) is an invasive beetle native to Asia that infests and
kills ash (Fraxinus spp.) in North America. Previous experiments indicated that
larvae feeding on co-evolved, resistant Manchurian ash (F. mandshurica) have
increased antioxidant and quinone-protective enzyme activities compared to larvae
feeding on susceptible North American species. Here, we examined mechanisms of
host-generated oxidative and quinone-based stress and other putative defenses in
Manchurian ash and the closely related and chemically similar, but susceptible,
black ash (F. nigra), with and without exogenous application of methyl jasmonate
(MeJA) to induce resistance mechanisms. Peroxidase activities were 4.6-13.3 times
higher in Manchurian than black ash, although both species appeared to express
the same three peroxidase isozymes. Additionally, peroxidase-mediated protein
cross-linking activity was stronger in Manchurian ash. Polyphenol oxidase, beta
glucosidase, chitinase, and lipoxygenase activities also were greater in
Manchurian ash, but only lipoxygenase activity increased with MeJA application.
Phloem H2O2 levels were similar and were increased by MeJA application in both
species. Lastly, trypsin inhibitor activity was detected in methanol and water
extracts that were not allowed to oxidize, indicating the presence of phenolic
based trypsin inhibitors. However, no proteinaceous trypsin inhibitor activity
was detected in either species. In response to MeJA application, Manchurian ash
had higher trypsin inhibitor activity than black ash using the unoxidized water
extracts, but no treatment effects were detected using methanol extracts. Based
on these results we hypothesize that peroxidases, lignin polymerization, and
quinone generation contribute to the greater resistance to EAB displayed by
Manchurian ash.
PMID- 27484883
TI - Curcumin alleviates ischemia reperfusion-induced acute kidney injury through NMDA
receptor antagonism in rats.
AB - OBJECTIVE: The present study investigated the role of N-methyl-d-aspartate (NMDA)
receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)
induced acute kidney injury (AKI) in rats. METHODS: Rats were subjected to
bilateral renal I/R (40 min I, 24 hours R) to induce AKI. Kidney injury was
assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric
acid, potassium level, fractional excretion of sodium, and macroproteinuria.
Oxidative stress in renal tissues was assessed by measuring myeloperoxidase
activity, thiobarbituric acid reactive substances, superoxide anion generation,
and reduced glutathione content. Hematoxylin & eosin staining was done to assess
histological changes in renal tissues. Curcumin (30 and 60 mg/kg) was
administered one hour before subjecting rats to AKI. In separate groups, NMDA
receptor agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were
administered prior to curcumin treatment in rats followed by AKI. RESULTS: I/R
induced AKI was demonstrated by significant change in plasma and urine parameters
along with marked increase in oxidative stress and histological changes in renal
tissues that were aggravated with pretreatment of glutamic acid and spermidine in
rats. Administration of curcumin resulted in significant protection against AKI.
However, glutamic acid and spermidine pretreatments prevented curcumin-mediated
renoprotection. CONCLUSION: It is concluded that NMDA receptor antagonism
significantly contributes towards curcumin-mediated protection against I/R
induced AKI.
PMID- 27484884
TI - One-dimensional self-assembly of perylene-diimide dyes by unidirectional transit
of zeolite channel openings.
AB - Confined supramolecular architectures of chromophores are key components in
artificial antenna composites for solar energy harvesting and storage. A typical
fabrication process, based on the insertion of dye molecules into zeolite
channels, is still unknown at the molecular level. We show that slipping of
perylene diimide dyes into the one-dimensional channels of zeolite L and
travelling inside is only possible because of steric-interaction-induced
cooperative vibrational modes of the host and the guest. The funnel-like
structure of the channel opening, larger at the entrance, along with a
directionally asymmetric entrance-exit probability, ensures a favorable self
assembly process of the perylene units.
PMID- 27484885
TI - SUMO wrestles breaks to the nuclear ring's edge.
PMID- 27484886
TI - A putative adenosine kinase family protein possesses adenosine diphosphatase
activity.
AB - Adenosine kinase is a potential target for development of new types of drugs. The
COG1839 family has been defined as "adenosine-specific kinase" family based on
structural analysis and the adenosine-binding ability of a family member,
PAE2307. However, there has been no experimental evidence with regard to the
enzymatic function of this protein family. Here we measured the enzymatic
activity of TTHA1091, a COG1839 family protein from Thermus thermophilus HB8. The
phosphorylation of adenosine by TTHA1091 was undetectable when ATP or ADP were
used as phosphate donor. However, the degradation of ADP to AMP was detected,
indicating that this protein possessed adenosine diphosphatase (ADPase) activity.
The (ADPase) activity was inhibited by divalent cations and was specific to ADP
and CDP. Thus, this study provides the first experimental evidence for the
enzymatic function of the "adenosine-specific kinase" family and suggests a need
to reexamine its functional annotation.
PMID- 27484887
TI - Sugammadex facilitates early recovery after surgery even in the absence of
neuromuscular monitoring in patients undergoing laryngeal microsurgery: a single
center retrospective study.
AB - BACKGROUND: In many countries, routine clinical anaesthesia does not always
involve neuromuscular monitoring. In these clinical settings, the efficacy and
safety of sugammadex use has not yet been confirmed. We investigated the efficacy
and safety of sugammadex in the absence of neuromuscular monitoring. METHODS: One
hundred and forty patients who underwent laryngeal microsurgery with the use of
rocuronium as a neuromuscular blocking agent, without the use of a neuromuscular
monitoring device, were retrospectively investigated. The patients were randomly
chosen among all the patients who met the inclusion criteria at a tertiary
university hospital between July 2013 and February 2015 and were allocated to
group S (sugammadex group) or group P (pyridostigmine group) according to the
neuromuscular reversal agent administered. Five patients were excluded from
analysis and 135 patients completed the study. Primary outcome was extubation
time. Secondary outcomes were anaesthesia time, the correlation between
anaesthesia time and extubation time, the total amount of rocuronium, and
postoperative adverse events in the post-anaesthesia care unit (PACU). RESULTS:
Extubation time was significantly shorter in group S (6.3 +/- 3.9 min) than in
group P (9.0 +/- 5.4 min). Anaesthesia time was also significantly shorter in
group S (30.7 +/- 10.3 min) than in group P (35.8 +/- 12.6 min). In the patients
with an anaesthesia time of 30 min or less, there was a positive correlation
between anaesthesia time and extubation time in group P (r = 0.453), but there
was no significant relationship in group S. The total amount of rocuronium used
was higher in group S (0.62 +/- 0.11 mg kg(-1)) than in group P (0.38 +/- 0.14 mg
kg(-1)). Postoperative adverse events in the PACU were comparable between the
groups, except for tachycardia events: the incidence of tachycardia was
significantly lower in group S (8.0 %) than in group P (17.3 %). CONCLUSIONS:
Sugammadex could shorten anaesthesia and extubation times as well as recovery
time in the PACU and reduce postoperative hemodynamic complications in a clinical
setting in the absence of neuromuscular monitoring. This may enhance the
patients' recovery in the operating room and PACU while improving the
postoperative condition of patients. TRIAL REGISTRATION: The trial was registered
in the UMIN clinical trials registry ( www.umin.ac.jp/ctr/index/htm ; unique
trial number: UMIN000016602; registration number: R000019266 ; principal
investigator's name: Byung Gun Lim; date of registration: February 22, 2015).
PMID- 27484888
TI - [Is stress cardiovascular magnetic resonance really useful to detect ischemia and
predict events in patients with different cardiovascular risk profile?]
AB - OBJECTIVE: The aim of this study was to evaluate the diagnostic and prognostic
usefulness of stress cardiovascular magnetic resonance (stress CMR) in patients
with different cardiovascular risk profile and to assess if the degree of
hypoperfusion is important to guide clinical decisions. METHOD: We included
patients submitted to adenosine stress CMR to rule out myocardial ischemia. We
evaluated its diagnostic accuracy with likelihood ratio (LR) and its prognostic
value with survival curves and a Cox regression model. RESULTS: 295 patients were
studied. The positive LR was 3.40 and the negative one 0.47. The maximal
usefulness of the test was found in patients without previous ischemic
cardiomyopathy (positive LR 4.85), patients with atypical chest pain (positive LR
8.56), patients with low or intermediate cardiovascular risk (positive LR 3.87)
and those with moderate or severe hypoperfusion (positive LR 8.63). Sixty
cardiovascular major events were registered. The best survival prognosis was
found in patients with a negative result (p=0.001) or mild hypoperfusion
(p=0.038). In the multivariate analysis, a moderate or severe hypoperfusion
increased cardiovascular event probability (HR=2.2; IC 95% 1.26-3.92), with no
differences between a mild positive and a negative result (HR=0.93; IC 95% 0.38
2.28). CONCLUSIONS: Stress CMR was specially useful in patients with low or
intermediate cardiovascular risk, patients with atypical chest pain, patients
without previous ischemic cardiomyopathy and those with moderate or severe
hypoperfusion. Hypoperfusion degree was the main issue factor to guide clinical
decisions.
PMID- 27484889
TI - Development of a Novel Reverse Transcription Loop-Mediated Isothermal
Amplification Assay for the Rapid Detection of African Horse Sickness Virus.
AB - African horse sickness (AHS) is a disease of equids caused by African Horse
Sickness Virus (AHSV) and is transmitted by Culicoides midges. AHS is endemic in
sub-Saharan Africa, but during the past century, outbreaks of significant
economic importance and elevated mortality have been recorded in Northern African
countries, the Iberian and Arabian Peninsula, the Middle East and the Indian
subcontinent. Effective control combines the application of early warning
systems, accurate laboratory diagnosis and reporting, animal movement
restrictions, suitable vaccination and surveillance programs, and the
coordination of all these measures by efficient veterinary services. Conventional
reverse-transcriptase (RT) PCR (RT-PCR) and real-time RT-PCR (rRT-PCR) assays
have improved the sensitivity and rapidity of diagnosing AHS, resulting in the
adoption of these methods as recommended tests by the World Organisation for
Animal Health (OIE). However, currently these assays are only performed within
laboratory settings; therefore, the development of field diagnostics for AHS
would improve the fast implementation of control policies. Loop-mediated
isothermal amplification (LAMP) is an isothermal, autocycling, strand
displacement nucleic acid amplification technique which can be performed in the
field. LAMP assays are attractive molecular assays because they are simple to
use, rapid, portable and have sensitivity and specificity within the range of rRT
PCR. This study describes the development of a novel RT-LAMP assay for the
detection of AHSV. The AHSV RT-LAMP assay has an analytical sensitivity of 96.1%
when considering an rRT-PCR cut-off value of CT > 36, or 91.3% when no rRT-PCR
cut-off is applied. Diagnostic sensitivity and specificity were 100%. This assay
provides for a rapid and low cost AHS diagnostic for use in the field.
PMID- 27484890
TI - Dilatation of the initially non-aneurysmal ascending aorta after replacement of a
bicuspid versus tricuspid aortic valve.
AB - Objective To compare the aortic diameter after isolated aortic valve replacement
(AVR) in patients with a bicuspid (BAV) or tricuspid aortic valve (TAV) and an
initially normal ascending aorta. Methods Patients with an ascending aortic
diameter of < 45 mm who had undergone isolated AVR were studied. Ultrasonic
cardiographic measurements of the ascending aortic diameter made pre- and
postoperatively and follow-up data concerning adverse aortic events and death
were analyzed. Results A total of 613 patients were included in this
retrospective study; of these, 211 had a BAV and 402 had a TAV. In both groups,
the ascending aorta significantly expanded but was non-aneurysmal during follow
up; however, the difference between the two groups was not significant. Cox
regression analysis showed no significant effect associated with the presence of
a BAV on adverse aortic events or death. Conclusion Dilatation of the ascending
aorta was observed after AVR in both groups, but was not more pronounced in
patients with a BAV. Long-term follow-up for ascending aortic aneurysm is
necessary after AVR in both patients with a BAV and those with a TAV.
PMID- 27484891
TI - Parents' assessment of circadian preference in elementary school-aged children:
Validity and relations to educational outcomes.
AB - Meta-analyses suggest that morning-oriented students obtain better school grades
than evening-oriented students. This finding has generally been found for
students in high school using self-report data for the assessment of circadian
preference. Two studies (N = 2718/192) investigated whether these findings
generalize across samples (i.e. elementary school-aged students) and methods
(i.e. parent reports). These studies also explored whether the relation between
circadian preference and school achievement could be explained within an
expectancy-value framework. To this end, the Lark-Owl Chronotype Indicator (LOCI)
was modified to obtain parents' evaluations of their children's circadian
preference, while students completed a battery of assessments designed to explore
the test-criterion evidence. Structural equation modeling and correlational
analyses revealed: (1) morning and evening orientation were two separable factors
of children's circadian preference; (2) correlations with behavioral (e.g. sleep
and eating times) and psychological (e.g. cognitive ability) data supported the
test-criterion validity of both factors; (3) morning orientation was positively
related to school achievement and (4) consistent with an expectancy-value
framework this relation was mediated by children's academic self-concept (ASC).
These findings have important research and policy implications for considering
circadian preference in the schooling of elementary students.
PMID- 27484892
TI - Spin excitations in systems with hopping electron transport and strong position
disorder in a large magnetic field.
AB - We discuss the spin excitations in systems with hopping electron conduction and
strong position disorder. We focus on the problem in a strong magnetic field when
the spin Hamiltonian can be reduced to the effective single-particle Hamiltonian
and treated with conventional numerical technics. It is shown that in a 3D system
with Heisenberg exchange interaction the spin excitations have a delocalized part
of the spectrum even in the limit of strong disorder, thus leading to the
possibility of the coherent spin transport. The spin transport provided by the
delocalized excitations can be described by a diffusion coefficient. Non
homogenous magnetic fields lead to the Anderson localization of spin excitations
while anisotropy of the exchange interaction results in the Lifshitz localization
of excitations. We discuss the possible effect of the additional exchange-driven
spin diffusion on the organic spin-valve devices.
PMID- 27484893
TI - Chaperone mediated autophagy in aging: Starve to prosper.
AB - The major lysosomal proteolytic pathways essential for maintaining proper
cellular homeostasis are macroautophagy, chaperone-mediated autophagy (CMA) and
microautophagy. What differentiates CMA from the other types of autophagy is the
fact that it does not involve vesicle formation; the unique feature of this
pathway is the selective targeting of substrate proteins containing a CMA
targeting motif and the direct translocation into the lysosomal lumen, through
the aid of chaperones/co-chaperones localized both at the cytosol and the
lysosomes. CMA operates at basal conditions in most mammalian cell models
analyzed so far, but it is mostly activated in response to stressors, such as
trophic deprivation or oxidative stress. The activity of CMA has been shown to
decline with age and such decline, correlating with accumulation of
damaged/oxidized/aggregated proteins, may contribute to tissue dysfunction and,
possibly, neurodegeneration. Herein, we review the recent knowledge regarding the
molecular components, regulation and physiology of the CMA pathway, the
contribution of impaired CMA activity to poor cellular homeostasis and
inefficient response to stress during aging, and discuss the therapeutic
opportunities offered by the restoration of CMA-dependent proteolysis in age
associated degenerative diseases.
PMID- 27484894
TI - Cerebral circulation in aging.
AB - Cerebral circulation is known to be protected by the regulatory function against
the hypoperfusion that will affect the cognitive function as a result of brain
ischemia and energy failure. The regulatory function includes cerebrovascular
autoregulation, chemical control, metabolic control, and neurogenic control, and
those compensatory mechanisms can be influenced by hypertension, atherosclerosis,
cardiac diseases, cerebrovascular diseases and aging. On the other hand, large
and/or small infarction, intracranial hemorrhage, subarachnoid hemorrhage,
atherosclerosis, amylod angiopathy are also more directly associated with
cognitive decline not only in those with vascular cognitive impairment or
vascular dementia but also those with Alzheimer's disease.
PMID- 27484895
TI - Testing patient targeted therapies in patients with temporomandibular joint
disorder with the arthrokinetic reflex: individual patient research.
AB - Traditional research in the health sciences has involved control and experimental
groups of patients, and descriptive and inferential statistical analyses
performed on the measurements obtained from the samples in each group. As the
novel model of translational healthcare, which integrates translational research
and translational effectiveness, becomes increasingly established in modern
contemporary medicine, healthcare continues to evolve into a model of care that
is evidence-based, effectiveness-focused and patient-centered. Patient-centered
care and patient-targeted therapies require the timely and critical development
and validation of a new research paradigm, individual patient research (IPR), as
opposed to the customary group research approach. Here, we propose a model of
individual patient research to define and characterize the effectiveness of a
novel therapeutic intervention for temporomandibular joint disorder. The
intervention must be tailor-made for each individual patient, and the data from
each patient must be analyzed individually. We propose that this endeavor is best
achieved by means of an adaptive cluster randomized stepped wedge blinded
controlled trial, because it permit individual patient outcomes research and
analysis, ensures equipoise, and maintains adequate power. The patient targeted
therapies section of the Journal of Translational Medicine must endeavor to
facilitate the dissemination of studies that focus broadly on translational
research for the ultimate benefit of individual patients.
PMID- 27484897
TI - Giant spin-phonon bottleneck effects in evaporable vanadyl-based molecules with
long spin coherence.
AB - Vanadium(iv) complexes have recently shown record quantum spin coherence times
that in several circumstances are limited by spin-lattice relaxation. The role of
the environment and vibronic properties in the low temperature dynamics is here
investigated by a comparative study of the magnetization dynamics as a function
of crystallite size and the steric hindrance of the beta-diketonate ligands in
VO(acac)2 (1), VO(dpm)2 (2) and VO(dbm)2 (3) evaporable complexes (acac- =
acetylacetonate, dpm- = dipivaloylmethanate, and dbm- = dibenzoylmethanate). A
pronounced crystallite size dependence of the relaxation time is observed at
unusually high temperatures (up to 40 K), which is associated with a giant spin
phonon bottleneck effect. We model this behaviour by an ad hoc force field
approach derived from density functional theory calculations, which evidences a
correlation of the intensity of the phenomenon with ligand dimensions and the
unit cell size.
PMID- 27484896
TI - LncRNA HOTAIR controls the expression of Rab22a by sponging miR-373 in ovarian
cancer.
AB - Increasing evidence suggests that the long non-coding RNA, HOX transcript
antisense intergenic RNA (HOTAIR) is widely involved in the progression and
metastasis of cancer. However, the specific role of HOTAIR in ovarian
carcinogenesis remains to be fully elucidated. In the present study, the levels
of HOTAIR were detected in 30 paired cancer and noncancer tissues using reverse
transcription-quantitative polymerase chain reaction analysis. The effect of
HOTAIR on the ovarian cancer cells was examined by overexpression or small
interfering RNA interference experiments. To examine the competitive endogenous
RNA (ceRNAs) mechanism, a luciferase reporter assay was used. In patients with
ovarian cancer, HOTAIR was significantly upregulated. Furthermore, the
upregulation of HOTAIR increased the proliferation, migration and invasion of
ovarian cancer cells. By contrast, the knockdown of HOTAIR repressed cell
invasion and viability. HOTAIR functioned as a ceRNA, and acted as a sink for
microRNA (miR)-373, thereby regulating the expression of Rab22a. The upregulation
of HOTAIR contributed to the malignant progression of ovarian cancer cells.
Therefore, the positive regulation between HOTAIR and Rab22a can be partially
attributed to the ceRNA regulatory network through miR-373.
PMID- 27484898
TI - Amitraz and its metabolite differentially activate alpha- and beta-adrenergic
like octopamine receptors.
AB - BACKGROUND: Amitraz is a formamidine acaricide and insecticide used to control
ticks, mites and fleas. N2 -(2,4-Dimethylphenyl)-N1 -methyformamidine (DPMF), a
metabolite of amitraz, is thought to be an active agent that exerts acaricidal
and insecticidal effects by acting as an agonist on octopamine receptors. The
emergence of cattle ticks resistant to amitraz is a serious problem that requires
urgent attention. The objective of this research was to determine which type of
octopamine receptor is the primary target of amitraz and thereby understand the
molecular mechanisms of action and resistance to amitraz. RESULTS: Amitraz and
DPMF potently activated Bombyx mori alpha- and beta-adrenergic-like octopamine
receptors (alpha- and beta-AL OARs) that were stably expressed in HEK-293 cells.
Notably, DPMF elevated intracellular cAMP levels, with an EC50 of 79.6 pm in beta
AL OARs, the transcripts of which were prevalently and widely localised in B.
mori body parts. Furthermore, DPMF elevated the intracellular Ca2+ levels, with
an EC50 of 1.17 nm in alpha-AL OARs. CONCLUSION: Although both amitraz and DPMF
acted as OAR agonists, the metabolite DPMF was more potent than amitraz and
differentially activated alpha- and beta-AL OARs. The present findings provide a
basis for studies to examine the mechanism of amitraz resistance and to develop
novel acaricides and insecticides. (c) 2016 Society of Chemical Industry.
PMID- 27484900
TI - Chemotherapy and radiation therapy elicits tumor specific T cell responses in a
breast cancer patient.
AB - BACKGROUND: Experimental evidence and clinical studies in breast cancer suggest
that some anti-tumor therapy regimens generate stimulation of the immune system
that accounts for tumor clinical responses, however, demonstration of the
immunostimulatory power of these therapies on cancer patients continues to be a
formidable challenge. Here we present experimental evidence from a breast cancer
patient with complete clinical response after 7 years, associated with
responsiveness of tumor specific T cells. METHODS: T cells were obtained before
and after anti-tumor therapy from peripheral blood of a 63-years old woman
diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated
with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac
toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after
8 months of treatment. Using in vitro cell cultures stimulated with autologous
monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we
characterize by flow cytometry the phenotype of tumor associated antigens (TAAs)
HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vbeta
repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes
(TILs) were performed in order to correlate both repertoires prior and after
therapy. RESULTS: We evidence a functional recovery of T cell responsiveness to
polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide
pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti
tumor therapy. The ex vivo analysis of the TCR-Vbeta repertoire of TAA specific T
cells in blood and TILs showed that whereas the TCR-Vbeta04-02 clonotype is
highly expressed in TILs the HER2/neu specific T cells are expressed mainly in
blood after therapy, suggesting that this particular TCR was selectively enriched
in blood after anti-tumor therapy. CONCLUSIONS: Our results show the benefits of
anti-tumor therapy in a breast cancer patient with clinical complete response in
two ways, by restoring the responsiveness of T cells by increasing the frequency
and activation in peripheral blood of tumor specific T cells present in the tumor
before therapy.
PMID- 27484899
TI - BRG1 interacts with GLI2 and binds Mef2c gene in a hedgehog signalling dependent
manner during in vitro cardiomyogenesis.
AB - BACKGROUND: The Hedgehog (HH) signalling pathway regulates cardiomyogenesis in
vivo and in differentiating P19 embryonal carcinoma (EC) cells, a mouse embryonic
stem (mES) cell model. To further assess the transcriptional role of HH
signalling during cardiomyogenesis in stem cells, we studied the effects of
overexpressing GLI2, a primary transducer of the HH signalling pathway, in mES
cells. RESULTS: Stable GLI2 overexpression resulted in an enhancement of cardiac
progenitor-enriched genes, Mef2c, Nkx2-5, and Tbx5 during mES cell
differentiation. In contrast, pharmacological blockade of the HH pathway in mES
cells resulted in lower expression of these genes. Mass spectrometric analysis
identified the chromatin remodelling factor BRG1 as a protein which co
immunoprecipitates with GLI2 in differentiating mES cells. We then determined
that BRG1 is recruited to a GLI2-specific Mef2c gene element in a HH signalling
dependent manner during cardiomyogenesis in P19 EC cells, a mES cell model.
CONCLUSIONS: Thus, we propose a mechanism where HH/GLI2 regulates the expression
of Mef2c by recruiting BRG1 to the Mef2c gene, most probably via chromatin
remodelling, to ultimately regulate in vitro cardiomyogenesis.
PMID- 27484902
TI - Identification of endoplasmic reticulum-shaping proteins in Plasmodium parasites.
PMID- 27484901
TI - Motor neuron-derived Thsd7a is essential for zebrafish vascular development via
the Notch-dll4 signaling pathway.
AB - BACKGROUND: Development of neural and vascular systems displays astonishing
similarities among vertebrates. This parallelism is under a precise control of
complex guidance signals and neurovascular interactions. Previously, our group
identified a highly conserved neural protein called thrombospondin type I domain
containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell
migration, tube formation and sprouting. In addition, we showed that thsd7a could
be detected in the nervous system and was required for intersegmental vessels
(ISV) patterning during zebrafish development. However, the exact origin of
THSD7A and its effect on neurovascular interaction remains unclear. RESULTS: In
this study, we discovered that zebrafish thsd7a was expressed in the primary
motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron
formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic
zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct
phenotypes that are very similar to the loss of Notch-delta like 4 (dll4)
signaling. Transcript profiling further revealed that expression levels of
notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in
the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate
angiogenic sprouting via Notch-dll4 signaling during development. CONCLUSIONS:
Our results suggested that motor neuron-derived Thsd7a plays a significant role
in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch
dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development
of both neural and vascular systems.
PMID- 27484903
TI - Beyond the classroom lecture: Liang Wang's personal war on tuberculosis in China.
PMID- 27484904
TI - Elimination of the geomagnetic field stimulates the proliferation of mouse neural
progenitor and stem cells.
AB - Living organisms are exposed to the geomagnetic field (GMF) throughout their
lifespan. Elimination of the GMF, resulting in a hypogeomagnetic field (HMF),
leads to central nervous system dysfunction and abnormal development in animals.
However, the cellular mechanisms underlying these effects have not been
identified so far. Here, we show that exposure to an HMF (<200 nT), produced by a
magnetic field shielding chamber, promotes the proliferation of neural
progenitor/stem cells (NPCs/NSCs) from C57BL/6 mice. Following seven-day HMF
exposure, the primary neurospheres (NSs) were significantly larger in size, and
twice more NPCs/NSCs were harvested from neonatal NSs, when compared to the GMF
controls. The self-renewal capacity and multipotency of the NSs were maintained,
as HMF-exposed NSs were positive for NSC markers (Nestin and Sox2), and could
differentiate into neurons and astrocyte/glial cells and be passaged
continuously. In addition, adult mice exposed to the HMF for one month were
observed to have a greater number of proliferative cells in the subventricular
zone. These findings indicate that continuous HMF-exposure increases the
proliferation of NPCs/NSCs, in vitro and in vivo. HMF-disturbed NPCs/NSCs
production probably affects brain development and function, which provides a
novel clue for elucidating the cellular mechanisms of the bio-HMF response.
PMID- 27484905
TI - The effect of door-to-balloon delay in primary percutaneous coronary intervention
on clinical outcomes of STEMI: a systematic review and meta-analysis protocol.
AB - BACKGROUND: Acute myocardial infarction (AMI) is a medical emergency in which
sudden occlusion of coronary artery(ies) results in ischemia and necrosis of the
cardiac tissues. Reperfusion therapies that aim at reopening the occluded artery
remain the mainstay of treatment for AMI. Primary percutaneous coronary
intervention (PCI), which enables the restoration of blood flow by reopening the
occluded artery(ies) via a catheter with an inflatable balloon, is currently the
preferred treatment for AMI with ST segment elevation (STEMI). The door-to
balloon (D2B) delay refers to the time interval counting from the arrival of a
patient with STEMI at a hospital to the time of the balloon inflation (or stent
deployment) that reopens the occluded artery(ies). Reducing this delay in primary
PCI is thought to be an important strategy toward achieving better patient
outcomes. Unfortunately, significant reduction of D2B delay in the USA over the
last decade has not been shown to be associated with improved STEMI mortality. It
has been suggested that the lack of impact could be due to the expanding use of
primary PCI in STEMI as well as the survival cohort effect, leading to a shift
toward a higher risk population receiving the procedure. Others have suggested
that reduction in D2B delay may not be as impactful as expected, given that it
only represents a small fraction of the total ischemic time. Although most
existing evidence have pointed to the presence of a beneficial effect of shorter
D2B delay, some inconsistencies however exist. This study aims to synthesize
available evidence in order to answer the following questions: (1) what is the
overall effect of D2B delay on clinical outcomes in patients with STEMI treated
with primary PCI? (2) What factors explain the differences of the effect
estimates among the studies? (3) What are the important strength and limitation
of the existing body of evidence? METHOD: We will search PubMed/MEDLINE, EMBASE,
ClinicalTrials.gov, WHO International Clinical Trials Registry, CINAHL Database,
and the Cochrane Library using a predefined search strategy. Other sources of
literature will include proceedings from the European Society of Cardiology, the
American College of Cardiology, the American Heart Association, the EUROPCR, and
the ProQuest Dissertations and Theses Database. We will include data from
observational studies (case-control and cohort study design) and randomized
control trials (that have investigated the relationship of D2B time and clinical
outcome(s) in an adult (older than 18) STEMI population). Mortality (cardiac
related and all-cause) and incidence heart failure (HF) have been prioritized as
the primary outcomes. All eligible studies will be assessed for risk of bias
using the Risk Of Bias in Non-randomized Studies - of Interventions tool. The
Grading of Recommendations, Assessment, and Evaluation (GRADE) framework will be
used to report the quality of evidence and strength of recommendations. We will
proceed to analyze the data quantitatively if the pre-specified conditions are
satisfied. DISCUSSION: Recent discussion on the negative findings of improved D2B
delay over time being unrelated to better STEMI outcomes at the population level
has reminded us of an important knowledge gap we have on this domain. This
systematic review will serve to address some of these key questions not
previously examined. Answers to these questions could clarify the controversies
and offer empirical support for or against the suggested hypotheses. SYSTEMATIC
REVIEW REGISTRATION: PROSPERO CRD42015026069.
PMID- 27484906
TI - MicroRNA-203 As a Stemness Inhibitor of Glioblastoma Stem Cells.
AB - Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all
glioblastoma (GBM) cells that are in large part responsible for tumor growth and
the high grade of therapeutic resistance that is so characteristic of GBM.
MicroRNAs (miR) have been implicated in regulating the expression of oncogenes
and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are
a potential target for cancer therapy. In the current study, miR-203 expression
was reduced in CD133(+) GBM-SCs derived from six human GBM biopsies. MicroRNA-203
transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere
assay and increased expression of glial and neuronal differentiation markers. In
addition, a reduced proliferation rate and an increased rate of apoptosis were
observed. Therefore, miR-203 has the potential to reduce features of stemness,
specifically in GBM-SCs, and is a logical target for GBM gene therapy.
PMID- 27484907
TI - Epigenetic and Glucocorticoid Receptor-Mediated Regulation of Glutathione
Peroxidase 3 in Lung Cancer Cells.
AB - Glutathione peroxidase 3 (GPx3), an antioxidant enzyme, acts as a modulator of
redox signaling, has immunomodulatory function, and catalyzes the detoxification
of reactive oxygen species (ROS). GPx3 has been identified as a tumor suppressor
in many cancers. Although hyper-methylation of the GPx3 promoter has been shown
to down-regulate its expression, other mechanisms by which GPx3 expression is
regulated have not been reported. The aim of this study was to further elucidate
the mechanisms of GPx3 regulation. GPx3 gene analysis predicted the presence of
ten glucocorticoid response elements (GREs) on the GPx3 gene. This result
prompted us to investigate whether GPx3 expression is regulated by the
glucocorticoid receptor (GR), which is implicated in tumor response to
chemotherapy. The corticosteroid dexamethasone (Dex) was used to examine the
possible relationship between GR and GPx3 expression. Dex significantly induced
GPx3 expression in H1299, H1650, and H1975 cell lines, which exhibit low levels
of GPx3 expression under normal conditions. The results of EMSA and ChIP-PCR
suggest that GR binds directly to GRE 6 and 7, both of which are located near the
GPx3 promoter. Assessment of GPx3 transcription efficiency using a luciferase
reporter system showed that blocking formation of the GR-GRE complexes reduced
luciferase activity by 7-8-fold. Suppression of GR expression by siRNA
transfection also induced down-regulation of GPx3. These data indicate that GPx3
expression can be regulated independently via epigenetic or GR-mediated
mechanisms in lung cancer cells, and suggest that GPx3 could potentiate
glucocorticoid (GC)-mediated anti-inflammatory signaling in lung cancer cells.
PMID- 27484908
TI - Expanding the clinical spectrum of COL1A1 mutations in different forms of
glaucoma.
AB - BACKGROUND: Primary congenital glaucoma (PCG) and early onset glaucomas are one
of the major causes of children and young adult blindness worldwide. Both
autosomal recessive and dominant inheritance have been described with involvement
of several genes including CYP1B1, FOXC1, PITX2, MYOC and PAX6. However,
mutations in these genes explain only a small fraction of cases suggesting the
presence of further candidate genes. METHODS: To elucidate further genetic causes
of these conditions whole exome sequencing (WES) was performed in an Italian
patient, diagnosed with PCG and retinal detachment, and his unaffected parents.
Sanger sequencing of the complete coding region of COL1A1 was performed in a
total of 26 further patients diagnosed with PCG or early onset glaucoma.
Exclusion of pathogenic variations in known glaucoma genes as CYP1B1, MYOC,
FOXC1, PITX2 and PAX6 was additionally done per Sanger sequencing and Multiple
Ligation-dependent Probe Amplification (MLPA) analysis. RESULTS: In the patient
diagnosed with PCG and retinal detachment, analysis of WES data identified
compound heterozygous variants in COL1A1 (p.Met264Leu; p.Ala1083Thr). Targeted
COL1A1 screening of 26 additional patients detected three further heterozygous
variants (p.Arg253*, p.Gly767Ser and p.Gly154Val) in three distinct subjects: two
of them diagnosed with early onset glaucoma and mild form of osteogenesis
imperfecta (OI), one patient with a diagnosis of PCG at age 4 years. All five
variants affected evolutionary, highly conserved amino acids indicating important
functional restrictions. Molecular modeling predicted that the heterozygous
variants are dominant in effect and affect protein stability and thus the amount
of available protein, while the compound heterozygous variants act as recessive
alleles and impair binding affinity to two main COL1A1 binding proteins: Hsp47
and fibronectin. CONCLUSIONS: Dominant inherited mutations in COL1A1 are known
causes of connective tissues disorders such as OI. These disorders are also
associated with different ocular abnormalities, although recognition of the
common pathology for both features is seldom being recognized. Our results expand
the role of COL1A1 mutations in different forms of early-onset glaucoma with and
without signs of OI. Thus, we suggest including COL1A1 mutation screening in the
genetic work-up of glaucoma cases and detailed ophthalmic examinations with
fundus analysis in patients with OI.
PMID- 27484909
TI - Alginate Microfiber System for Expansion and Direct Differentiation of Human
Embryonic Stem Cells.
AB - Pluripotent human embryonic stem cells (hESCs) are a potential renewable cell
source for regenerative medicine and drug testing. To obtain adequate cell
numbers for these applications, there is a need to develop scalable cell culture
platforms to propagate hESCs. In this study, we encapsulated hESCs in calcium
alginate microfibers as single cells, for expansion and differentiation under
chemically defined conditions. hESCs were suspended in 1% (w/v) alginate solution
at high cell density (>10(7) cells/mL) and extruded at 5 m/min into a low calcium
concentration bath (10 mM) for gelation. Mild citrate buffer (2.5 mM), which did
not affect hESCs viability, was used to release the cells from the calcium
alginate hydrogel. Encapsulation as single cells was critical, as this allowed
the hESCs to grow in the form of relatively small and uniform aggregates. This
alginate microfiber system allowed for expansion of an hESC line, HUES7, for up
to five passages while maintaining pluripotency. Immunohistochemistry, polymerase
chain reaction, and other analyses showed that passage 5 (P5) HUES7 cells
expressed proteins and genes characteristic of pluripotent stem cells, possessed
normal karyotype, and were able to form representative tissues of the three
embryonic germ layers in vitro and in vivo. Encapsulated HUES7 cells at P5 could
also be induced to directly differentiate into liver-like cells. Collectively,
our experiments show that the alginate microfiber system can be used as a three
dimensional cell culture platform for long-term expansion and differentiation of
hESCs under defined conditions.
PMID- 27484910
TI - Identification of a novel beta-adrenergic octopamine receptor-like gene (betaAOR
like) and increased ATP-binding cassette B10 (ABCB10) expression in a
Rhipicephalus microplus cell line derived from acaricide-resistant ticks.
AB - BACKGROUND: The cattle tick Rhipicephalus (Boophilus) microplus is an
economically important parasite of livestock. Effective control of ticks using
acaricides is threatened by the emergence of resistance to many existing
compounds. Several continuous R. microplus cell lines have been established and
provide an under-utilised resource for studies into acaricide targets and
potential genetic mutations associated with resistance. As a first step to
genetic studies using these resources, this study aimed to determine the presence
or absence of two genes and their transcripts that have been linked with
acaricide function in cattle ticks: beta-adrenergic octopamine receptor (betaAOR,
associated with amitraz resistance) and ATP-binding cassette B10 (ABCB10,
associated with macrocyclic lactone resistance) in six R. microplus cell lines,
five other Rhipicephalus spp. cell lines and three cell lines representing other
tick genera (Amblyomma variegatum, Ixodes ricinus and Hyalomma anatolicum).
METHODS: End-point polymerase chain reaction (PCR) was used for detection of the
betaAOR gene and transcripts in DNA and RNA extracted from the tick cell lines,
followed by capillary sequencing of amplicons. Quantitative real-time PCR (qPCR)
was performed to determine the levels of expression of ABCB10. RESULTS: betaAOR
gene expression was detected in all Rhipicephalus spp. cell lines. We observed a
second amplicon of approximately 220 bp for the betaAOR gene in the R. microplus
cell line BME/CTVM6, derived from acaricide-resistant ticks. Sequencing of this
transcript variant identified a 36 bp insertion in the betaAOR gene, leading to a
12-amino acid insertion (LLKTLALVTIIS) in the first transmembrane domain of the
protein. In addition, nine synonymous SNPs were also discovered in R.
appendiculatus, R. evertsi and R. sanguineus cell lines. Some of these SNPs
appear to be unique to each species, providing potential tools for
differentiating the tick species. The BME/CTVM6 cell line had significantly
higher ABCB10 (P = 0.002) expression than the other R. microplus cell lines.
CONCLUSIONS: The present study has identified a new betaAOR gene and demonstrated
a higher ABCB10 expression level in the BME/CTVM6 cell line, indicating that tick
cell lines provide a useful experimental tool for acaricide resistance studies
and further elucidation of tick genetics.
PMID- 27484911
TI - Giant ventral hernia-relationship between abdominal wall muscle strength and
hernia area.
AB - BACKGROUND: Symptoms arising from giant ventral hernia have been considered to be
related to weakening of the abdominal muscles. The aim of this study was to
investigate the relationship between the area of the abdominal wall defect and
abdominal wall muscle strength measured by the validated BioDex system together
with a back/abdominal unit. METHODS: Fifty-two patients with giant ventral hernia
(>10 cm wide) underwent CT scan, clinical measurement of hernia size and BioDex
measurement of muscle strength prior to surgery. The areas of the hernia derived
from CT scan and from clinical measurement were compared with BioDex forces in
the modalities extension, flexion and isometric contraction. The Spearman rank
test was used to calculate correlations between area, BMI, gender, age, and
muscle strength. RESULT: The hernia area calculated from clinical measurements
correlated to abdominal muscle strength measured with the Biodex for all
modalities (p-values 0.015-0.036), whereas no correlation was seen with the area
calculated by CT scan. No relationship was seen between BMI, gender, age and the
area of the hernia. DISCUSSION: The inverse correlation between BioDex abdominal
muscle strength and clinically assessed hernia area, seen in all modalities, was
so robust that it seems safe to conclude that the area of the hernia is an
important determinant of the degree of loss of abdominal muscle strength. Results
using hernia area calculated from the CT scan showed no such correlation and this
would seem to concur with the results from a previous study by our group on
patients with abdominal rectus diastasis. In that study, defect size assessed
clinically, but not that measured by CT scan, was in agreement with the size of
the diastasis measured intra-operatively. The point at which the area of a hernia
begins to correlate with loss of abdominal wall muscle strength remains unknown
since this study only included giant ventral hernias.
PMID- 27484912
TI - Peripheral nervous system assessment in acromegaly patients under somatostatin
analogue therapy.
AB - PURPOSE: Acromegaly is known to affect peripheral nervous system (PNS) causing
carpal tunnel syndrome (CTS) and polyneuropathy. The frequency of these disorders
and the evaluation methods vary among studies. In the present study, we aimed to
examine PNS of acromegaly patients under somatostatin analogue (SSA) therapy.
METHODS: Forty-eight acromegaly patients (26 F/22 M, 45.58 +/- 11.6 years) under
SSA treatment and 44 healthy controls (25 F/19 M, 47.46 +/- 8.7 years) were
assessed by symptom questionnaires, neurologic examination and
electrophysiological studies. RESULTS: 87.5 % of the acromegaly patients had at
least one abnormal finding regarding PNS. With the incorporation of palm-wrist
median nerve conduction velocity method, we detected CTS in 50 % of patients.
Polyneuropathy was less frequent (29.2 %). Both conditions were independent from
the coexisting diabetes mellitus (p = 0.22 for CTS, p = 0.71 for polyneuropathy).
Polyneuropathy but not CTS was more common among biochemically uncontrolled
acromegaly patients rather than those under control (p = 0.03; p = 0.68,
respectively). CONCLUSION: Our findings emphasize the high prevalence of
peripheral nervous system involvement in acromegaly patients under SSA therapy
and importance of neurological evaluation of these patients. Early diagnosis and
treatment of the disease may reduce the PNS involvement.
PMID- 27484913
TI - Malignant peritoneal mesothelioma and Crohn disease.
AB - AIMS: Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma
(MM) has been reported in the setting of Crohn ileitis. To our knowledge,
peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not
been reported. The purpose of this study is to report the clinicopathological
characteristics of patients with peritoneal MM and IBD. METHODS: A database of
approximately 3800 MM was reviewed for cases of MM in patients with IBD. RESULTS:
Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified,
including two women and one man ranging in age from 56 to 65 years. All had a
long-standing history of diarrhoea and an established diagnosis of CD of 3 years
or greater duration. Two had epithelial MM and one had biphasic MM. Only one had
documented asbestos exposure. CONCLUSIONS: Peritoneal MM occurs rarely in
patients with IBD, but interestingly, has only been observed in the setting of CD
and not in patients with ulcerative colitis. Chronic inflammation has been
associated with the development of MM in rare instances and these three cases
suggest that CD with transmural inflammation may also be a precursor. The precise
role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM
remains to be determined.
PMID- 27484914
TI - HBME-1 is expressed by erythroid precursors in early maturation stage and can be
a valuable tool for evaluation of dyserythropoiesis in bone marrow core biopsy
specimens.
AB - The reaction of Hector Battifora mesothelial epitope-1 (HBME-1) antibody with
scattered pronormoblasts in normal bone marrow core biopsy specimens has been
reported. This study evaluated the immunohistochemical profile of HBME-1 in a
panel of 52 normal, dyserythropoietic and neoplastic marrow samples. We compared
the staining property of HBME-1 with that of the commonly used erythroid marker,
glycophorin A (CD235a) and in each case, we semi-quantitatively evaluated the
HBME-1/CD235a-positive cells ratio. In normal samples, HBME-1 labelled scattered
immature erythroid precursors. In dyserythropoietic specimens, HBME-1 stained
nucleated erythroid precursors in varying degrees, from pronormoblast through
normoblast stages, with the highest intensity in immature forms. Overall, the
cellular background of non-erythroid progenitors, erythrocytes and neoplastic
cells did not react with HBME-1, except in leukaemia cases with myelodysplasia
related changes. Our study shows that HBME-1 is a useful marker to identify
immature erythroid precursors and that an HBME-1/CD235a-positive cells ratio
>=10% is associated with dyserythropoiesis.
PMID- 27484915
TI - The impact of alcohol care teams on emergency secondary care use following a
diagnosis of alcoholic liver disease - a national cohort study.
AB - BACKGROUND: The increasing mortality rates from alcohol-related liver disease
(ARLD) are a public health concern. To address this, alcohol care teams (ACT)
case-find and lead management of alcohol issues for these patients. Local
assessments of ACTs have shown reductions in emergency admissions and emergency
department attendances. We examine the impact of ACTs on emergency hospital
activity following a diagnosis of ARLD. METHODS: Administrative Hospital Episode
Statistics (HES) data were extracted. Information on ACT provision at English NHS
hospital trusts and sites in 2009/10 was taken from a survey by Public Health
England. We undertook a difference-in-difference analysis to compare emergency
hospital activity for a cohort of individuals diagnosed with ARLD who presented
to hospitals either with or without an ACT in the one year before and after a
first ARLD diagnosis during 2009/10. RESULTS: Over the study period, 9,165
individuals eligible for inclusion in our study had a first diagnosis of ARLD.
4,768 presented to one of 41 hospital trusts with an ACT (59 sites) and 4,397
presented to one of 50 non-ACT hospital trusts (65 sites). Whilst age and sex
demographics were similar between the two cohorts, the ACT hospital cohort had a
higher proportion of individuals in the most deprived quintile (41.6 % v 28.5 % p
< .0001). In the difference-in-difference analysis, the presence of an ACT at a
hospital trust was not associated with a change in all-cause emergency admissions
(0.020 (95 % CI -0.070, 0.111), p = 0.656), alcohol-related emergency admissions
(-0.025 (95 % CI -0.104, 0.054), p = 0.536) or all-cause emergency department
attendances (0.042 (95 % CI -0.087, 0.171), p = 0.521). Sensitivity analyses by
sex and hospital site did not affect the study findings. CONCLUSIONS: In this
study, the presence of an ACT at the NHS hospital trust where individuals have
their first recorded diagnosis of ARLD does not appear to be associated with
subsequent emergency hospital activity within these populations. Further analysis
focussing on the components and specific effects of ACT interventions on
individuals and systems both pre- and post-diagnosis of ARLD may reveal important
avenues to improve care.
PMID- 27484916
TI - Local Treatment of Penile Prosthesis Infection as Alternative to Immediate
Salvage Surgery.
AB - INTRODUCTION: Penile prosthesis (PP) is the established treatment for patients
with erectile dysfunction (ED) who do not respond to phosphodiesterase inhibitors
and intracavernosal injections. In general, these devices have been largely
successful but there are not free of serious complication such as PP infection
(PPI). PPI requires immediate surgical removal or salvage rescue of the PP. AIM:
In this report, we present two clinical cases with inflatable PP (IPP) treated
locally with antibiotic and high pressure irrigation and then avoid the PP
removal or salvage rescue. METHODS: We present two patients with PPI in our
institution and literature review. MAIN OUTCOME MEASURES: Resolution of the two
cases. RESULTS: Patient A (A) was 44 years old and patient B (B) 51 years old
presented PPI after three weeks (A) and eight weeks (B). Both patients were
diabetic. Physical exploration revealed an open scrotal incision at its margin
with a clear discharge. The rest of the incision and scrotum were clean and dry.
They had not scrotum pain/tenderness or systemic/septic symptoms. The bacterial
culture of the incisional drainage revealed a Staphylococcus aureus (A) and
Staphylococcus epidermidis (B). In both cases, we performed an excision of the
tissue around the pump with a high pressure pulsed irrigation (Interpulse;
Stryker Corp, Kalamazoo, MI, USA). For the irrigation we used three different
solutions that included povidone-iodine, antibiotics (gentamicin plus
vancomicin), and hydrogen peroxyde. Finally, we performed a multilayered surgical
closure with the use of aspirate drainage over 24 hours and intravenous
antibiotics. The patients had a total resolution of its symptoms after 20 months
(A) and 36 months (B), and the IPP worked properly. CONCLUSION: This treatment
could be an option for to perform specific patients with local IPP infection
without systemic symptoms instead of surgical removal.
PMID- 27484917
TI - What Do Patients Want? A Needs Assessment of Vulvodynia Patients Attending a
Vulvar Diseases Clinic.
AB - INTRODUCTION: Vulvodynia is a chronic pain disorder that negatively impacts the
quality of life of affected women. AIM: The goal of this study was to identify
unmet needs among localized provoked vulvodynia patients. METHODS: A qualitative
needs assessment was performed in a subspecialized vulvar clinic in a single
academic institution in Canada. Semistructured interviews were conducted,
recorded, and analyzed using the constant comparative method of grounded theory
to identify common themes. MAIN OUTCOME MEASURES: Interviews were conducted until
theme saturation was achieved. RESULTS: A diverse sample of 8 patients completed
all components of the study. The most prominent unmet needs raised by patients in
their interviews were categorized into 3 main themes: (1) challenges related to
obtaining a diagnosis of vulvodynia and finding practitioners who are
knowledgeable about vulvodynia; (2) challenges related to the current impact of
the disease physically, emotionally, and in social relationships with patients'
intimate partners; and (3) barriers to adherence with recommended therapy.
Solutions recommended by patients include better education of physicians
regarding vulvodynia and the development of multidisciplinary programs that
provide access to physiotherapy, sex therapy, mindfulness and psychology services
on-site, information classes for new patients, and the creation of peer support
networks for patients and their partners. CONCLUSION: A patient-focused needs
assessment suggests optimal vulvodynia care requires better education of
physicians and a multimodal approach to therapy, ideally with multiple services
offered in 1 location.
PMID- 27484918
TI - A New Paradigm to Analyze Data Completeness of Patient Data.
AB - BACKGROUND: There is a need to develop a tool that will measure data completeness
of patient records using sophisticated statistical metrics. Patient data
integrity is important in providing timely and appropriate care. Completeness is
an important step, with an emphasis on understanding the complex relationships
between data fields and their relative importance in delivering care. This tool
will not only help understand where data problems are but also help uncover the
underlying issues behind them. OBJECTIVES: Develop a tool that can be used
alongside a variety of health care database software packages to determine the
completeness of individual patient records as well as aggregate patient records
across health care centers and subpopulations. METHODS: The methodology of this
project is encapsulated within the Data Completeness Analysis Package (DCAP)
tool, with the major components including concept mapping, CSV parsing, and
statistical analysis. RESULTS: The results from testing DCAP with Healthcare Cost
and Utilization Project (HCUP) State Inpatient Database (SID) data show that this
tool is successful in identifying relative data completeness at the patient,
subpopulation, and database levels. These results also solidify a need for
further analysis and call for hypothesis driven research to find underlying
causes for data incompleteness. CONCLUSION: DCAP examines patient records and
generates statistics that can be used to determine the completeness of individual
patient data as well as the general thoroughness of record keeping in a medical
database. DCAP uses a component that is customized to the settings of the
software package used for storing patient data as well as a Comma Separated
Values (CSV) file parser to determine the appropriate measurements. DCAP itself
is assessed through a proof of concept exercise using hypothetical data as well
as available HCUP SID patient data.
PMID- 27484919
TI - Resveratrol inhibits phosphorylation within the signal transduction and activator
of transcription 3 signaling pathway by activating sirtuin 1 in SW1353
chondrosarcoma cells.
AB - The present study assessed the mechanism by which resveratrol (Res) inhibits the
growth of SW1353 chondrosarcoma cells and examined whether sirtuin 1 (Sirt1)
activation affects phosphorylation within the signal transduction and activator
of transcription 3 (STAT3) signaling pathway. The present study used SW1353
chondrosarcoma cells in the logarithmic phase of growth (control and treatment
groups). The latter group was treated with Res at 25 and 50 umol/l for 24 h, and
cell viability, proliferation and apoptosis were analyzed using the cell counting
kit-8 assay, colony counting and Hoechst staining, respectively. The expression
levels of caspase-3, cleaved caspase-3, B-cell lymphoma-2 (BCL-2), BCL-2
associated X protein (Bax), STAT3 and phosphorylated (p-)STAT3) were measured by
Western blotting. SW1353 cells were transfected with small interfering (si)RNA
targeting Sirt1 and the expression levels of Sirt1, STAT3 and p-STAT3 were
assessed. Exposure of SW1353 cells to Res reduced cell viability in a dose
dependent manner (P<0.01). Additionally, cell proliferation was significantly
inhibited and the cell nuclei exhibited apoptotic characteristics. Cleaved
caspase-3, Sirt1 and Bax levels were upregulated. The expression levels of BCL-2
and p-STAT3 were downregulated. Additionally, the BCL-2/Bax ratio was reduced
compared with the control group. The total STAT3 level was unaffected. Res
treatment activated Sirt1, however, in cells transfected with Sirt1-siRNA, the
ability of resveratrol to suppress p-STAT3 expression was compromised. Overall,
it was revealed that Res treatment induced apoptosis, inhibited proliferation and
affected phosphorylation within the STAT3 signaling pathway by activating Sirt1
in SW1353 chondrosarcoma cells.
PMID- 27484920
TI - Effect of Tributyltin, Cadmium, and Their Combination on Physiological Responses
in Juvenile Grass Carp.
AB - Tributyltin (TBT) and cadmium (Cd) are two common pollutants in aquatic
environments. This study was designed to examine the physiological responses of
juvenile Grass Carp Ctenopharyngodon idella to TBT, Cd, and their combination.
Fish were apportioned into a control group, a TBT group (7.5 MUg/L), a Cd group
(2.97 mg/L), and a TBT-Cd group (7.5 MUg/L TBT, 2.97 mg/L Cd(2+)) for 7 d. The
following activities were measured: Na(+),K(+)-ATPase in gill tissues; nitric
oxide synthase (NOS), acetylcholinesterase (AChE), and monoamine oxidase (MAO) in
brain tissues; and lipid peroxidation (LPO), malondialdehyde (MDA), total
antioxidative capacity (T-AOC), and glutathione (GSH) in liver tissues. Cadmium
induced stress was suggested by alterations in antioxidant responses (MDA, LPO,
and T-AOC) and neurological parameters (AChE, MAO, and NOS). Cadmium also induced
Na(+),K(+)-ATPase and GSH activity. Compared with the responses among the Cd
group, the combination of TBT and Cd not only decreased the level of GSH and
Na(+),K(+)-ATPase but also increased the levels of MDA, LPO, AChE, MAO, and NOS.
These results suggest that a combination of TBT and Cd could reduce the adverse
effects of Cd on Grass Carp. However, the exact mechanisms for the combined
effects TBT and Cd on these biomarkers require further investigation. Received
September 28, 2015; accepted April 17, 2016.
PMID- 27484921
TI - Structural characterization of suppressor lipids by high-resolution mass
spectrometry.
AB - RATIONALE: Suppressor lipids were originally identified in 1993 and reported to
encompass six lipid classes that enable Saccharomyces cerevisiae to live without
sphingolipids. Structural characterization, using non-mass spectrometric
approaches, revealed that these suppressor lipids are very long chain fatty acid
(VLCFA)-containing glycerophospholipids with polar head groups that are typically
incorporated into sphingolipids. Here we report, for the first time, the
structural characterization of the yeast suppressor lipids using high-resolution
mass spectrometry. METHODS: Suppressor lipids were isolated by preparative
chromatography and subjected to structural characterization using hybrid
quadrupole time-of-flight and ion trap-orbitrap mass spectrometry. RESULTS: Our
investigation recapitulates the overall structural features of the suppressor
lipids and provides an in-depth characterization of their fragmentation pathways.
Tandem mass analysis identified the positionally defined molecular lipid species
phosphatidylinositol (PI) 26:0/16:1, PI mannoside (PIM) 16:0/26:0 and PIM
inositol-phosphate (PIMIP) 16:0/26:0 as abundant suppressor lipids. This finding
differs from the original study that only inferred the positional isomer PI
16:0/26:0 and prompts new insight into the biosynthesis of suppressor lipids.
Moreover, we also report the identification of a novel suppressor lipid featuring
an amino sugar residue linked to a VLCFA-containing PI molecule. CONCLUSIONS:
Fragmentation pathways of yeast suppressor lipids have been delineated. In
addition, the fragmentation information has been added to our open source ALEX
lipid database to support automated identification and quantitative monitoring of
suppressor lipids in yeast and bacteria that produce similar lipid molecules.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27484922
TI - After-hours primary care for people with intellectual disabilities in The
Netherlands-Current arrangements and challenges.
AB - BACKGROUND: Little is known about the organisation of after-hours primary care
for people with intellectual disabilities (ID), and mainstream care is not self
evidently accessible or fit for this group. A first step towards improvement is a
greater understanding of current after-hours primary ID care. AIMS: This study
explores the organisation of and experiences with after-hours primary care
provided for people with ID in The Netherlands. METHODS AND PROCEDURES: A
telephone survey amongst 68 care provider services including questions on
organisational characteristics, problem areas, facilitators, and inhibitors.
OUTCOMES AND RESULTS: A multitude of different after-hours primary care
arrangements were found. Primary care physicians (PCPs) were involved in almost
all care provider services, often in alliance with PCP cooperatives. Specialised
ID physicians had differing roles as gatekeeper, primary caregiver, or
consultant. Most problems during the after-hours arose regarding daily care
professionals' competences. Facilitators and inhibitors of after-hours primary
care were themed around complexity of, and need for, specialised care,
multidisciplinary team of professionals, communication and information, and
prerequisites at organisational level. CONCLUSIONS AND IMPLICATIONS: Evidence on
specific after-hours health needs of people with ID is needed to strengthen
collaboration between specialist ID care services and mainstream healthcare
services to adequately provide care.
PMID- 27484923
TI - Searching for rare diseases in PubMed: a blind comparison of Orphanet expert
query and query based on terminological knowledge.
AB - BACKGROUND: Despite international initiatives like Orphanet, it remains difficult
to find up-to-date information about rare diseases. The aim of this study is to
propose an exhaustive set of queries for PubMed based on terminological knowledge
and to evaluate it versus the queries based on expertise provided by the most
frequently used resource in Europe: Orphanet. METHODS: Four rare disease
terminologies (MeSH, OMIM, HPO and HRDO) were manually mapped to each other
permitting the automatic creation of expended terminological queries for rare
diseases. For 30 rare diseases, 30 citations retrieved by Orphanet expert query
and/or query based on terminological knowledge were assessed for relevance by two
independent reviewers unaware of the query's origin. An adjudication procedure
was used to resolve any discrepancy. Precision, relative recall and F-measure
were all computed. RESULTS: For each Orphanet rare disease (n = 8982), there was
a corresponding terminological query, in contrast with only 2284 queries provided
by Orphanet. Only 553 citations were evaluated due to queries with 0 or only a
few hits. There were no significant differences between the Orpha query and
terminological query in terms of precision, respectively 0.61 vs 0.52 (p = 0.13).
Nevertheless, terminological queries retrieved more citations more often than
Orpha queries (0.57 vs. 0.33; p = 0.01). Interestingly, Orpha queries seemed to
retrieve older citations than terminological queries (p < 0.0001). CONCLUSION:
The terminological queries proposed in this study are now currently available for
all rare diseases. They may be a useful tool for both precision or recall
oriented literature search.
PMID- 27484924
TI - Long-term functional outcomes following mesh-augmented posterior vaginal prolapse
repair.
AB - OBJECTIVE: To assess long-term patient-centered functional outcomes following
posterior vaginal wall repair using mesh implants. METHOD: The present
prospective telephone interview study enrolled a cohort of women who had
undergone posterior vaginal wall repair with mesh between January 1, 2006 and
February 28, 2009, at a single center in Israel. Patients were asked to report
long-term outcomes, and demographic, clinical, intraoperative, and postoperative
follow-up data were retrieved from patients' medical files. Multivariable
logistic regression models were used to asses associations between baseline
characteristics and long-term outcomes. RESULTS: In total, 102 patients were
contacted, with 80 (78.4%) at 61-83months after surgery agreeing to participate.
A recurrence of prolapse symptoms was reported by 14 patients (18%) (12 required
a corrective procedure), mesh had been removed from two patients owing to
erosion/extrusion, and two others had undergone removal of granulation tissue.
Long-term, bothersome symptoms were reported by 13 (16%) patients. Parity and
previous hysterectomy were associated with lower odds of long-term adverse
outcomes, and the location of the apical (C/D) pelvic organ prolapse
quantification point and a change in its position following surgery were
associated with increased odds of adverse outcomes. CONCLUSION: The long-term
adverse-outcome rate was low for patients who underwent posterior vaginal mesh
augmentation. These results highlight the importance of apical support for good
long-term functional outcomes.
PMID- 27484925
TI - Area under curve of temporal estradiol measurements for prediction of the
detrimental effect of estrogen exposure on implantation.
AB - OBJECTIVE: To assess whether the area under the curve of temporal estradiol
measurements (AUCEM) during cycles of assisted reproductive technology (ART) can
be used to predict failure of implantation and clinical pregnancy. METHODS: In a
prospective study, women aged 24-39years undergoing ART at a center in Turkey
were enrolled between January and December 2014. Eligible patients had a regular
menstrual cycle, normal levels of serum prolactin, and no hormone treatment
within the past 3months. The area under the curve of the time course of estradiol
measurements was calculated for each participant, and assessed for its ability to
predict successful implantation. RESULTS: Among 282 participants, 109 (38.6%)
women had successful implantation. There was a significant difference between the
two groups of women in AUCEM, estradiol per day (AUCEM divided by duration of
stimulation), and endometrial thickness on the day of human chorionic
gonadotropin administration (P<0.05 for all). CONCLUSION: The area under the
curve of estradiol measurements during ART cycles might be useful for predicting
failure of implantation and clinical pregnancy.
PMID- 27484927
TI - Defense Mechanism Card Pull in TAT Stories.
AB - This study investigates the question of whether different Thematic Apperception
Test (TAT; Murray, 1943 ) cards are likely to prompt stories that are
characterized by different defense mechanisms. This condition is known as card
pull and refers to the probability that different TAT cards elicit different
personality scores for the same variable. If so, the assessment of defense use
would be importantly influenced by the TAT cards used in an assessment. TAT
stories from 3 different community samples were examined (Ns = 91, 98, 121),
using a statistical method developed by Stein et al ( 2014 ). The results
indicated that different TAT cards pull for different defenses, as assessed by
the Defense Mechanism Manual (DMM: Cramer, 1991b ). However, the nature of card
pull was not always consistent across samples. These dissimilarities could be due
to group differences, or to the presence of different TAT cards used in the test
battery, indicating that card pull is importantly determined by context.
PMID- 27484926
TI - Cingulin and actin mediate midbody-dependent apical lumen formation during
polarization of epithelial cells.
AB - Coordinated polarization of epithelial cells is a key step during morphogenesis
that leads to the formation of an apical lumen. Rab11 and its interacting protein
FIP5 are necessary for the targeting of apical endosomes to the midbody and
apical membrane initiation site (AMIS) during lumenogenesis. However, the
machinery that mediates AMIS establishment and FIP5-endosome targeting remains
unknown. Here we identify a FIP5-interacting protein, Cingulin, which localizes
to the AMIS and functions as a tether mediating FIP5-endosome targeting. We
analysed the machinery mediating AMIS recruitment to the midbody and determined
that both branched actin and microtubules are required for establishing the site
of the nascent lumen. We demonstrate that the Rac1-WAVE/Scar complex mediates
Cingulin recruitment to the AMIS by inducing branched actin formation, and that
Cingulin directly binds to microtubule C-terminal tails through electrostatic
interactions. We propose a new mechanism for apical endosome targeting and AMIS
formation around the midbody during epithelial lumenogenesis.
PMID- 27484928
TI - Synaptic Basis for the Generation of Response Variation in Auditory Cortex.
AB - Cortical neurons can exhibit significant variation in their responses to the same
sensory stimuli, as reflected by the reliability and temporal precision of
spikes. However the synaptic mechanism underlying response variation still
remains unclear. Here, in vivo whole-cell patch-clamp recording of excitatory
neurons revealed variation in the amplitudes as well as the temporal profiles of
excitatory and inhibitory synaptic inputs evoked by the same sound stimuli in
layer 4 of the rat primary auditory cortex. Synaptic inputs were reliably induced
by repetitive stimulation, although with large variation in amplitude. The
variation in the amplitude of excitation was much higher than that of inhibition.
In addition, the temporal jitter of the synaptic onset latency was much smaller
than the jitter of spike response. We further demonstrated that the amplitude
variation of excitatory inputs can largely account for the spike variation, while
the jitter in spike timing can be primarily attributed to the temporal variation
of excitatory inputs. Furthermore, the spike reliability of excitatory but not
inhibitory neurons is dependent on tone frequency. Our results thus revealed an
inherent cortical synaptic contribution for the generation of variation in the
spike responses of auditory cortical neurons.
PMID- 27484929
TI - Gastroprotective potential of hydro-alcoholic extract of Pattanga (Caesalpinia
sappan Linn.).
AB - ETHNO-PHARMACOLOGICAL RELEVANCE: Pattanga is botanically equated as Caesalpinia
sappan Linn. (Family: Caesalpiniaceae) and is used in Ayurveda system of medicine
since ages. According to Ayurveda, useful part is Heartwood, which is bitter,
astringent and acrid and is useful in vitiated conditions of vata and pitta,
burning sensation, wounds, ulcers, leprosy, skin diseases, menorrhagia,
leucorrhea, and diabetes. It is used as a major ingredient in Ayurvedic
formulations and preparations like Patrangasava, Chandanadya Thalia, and
Karpuradyarka. AIM OF THE STUDY: The present study is planned to evaluate the
gastroprotective activity of the selected Ayurvedic drug using three different in
vivo gastric ulcer models, so as to provide scientific evidence for the Ayurvedic
claims. MATERIALS AND METHODS: For this study, Wistar albino rats fasted
overnight were selected. The hydroalcoholic extract of Caesalpinia sappan
heartwood at the dose level 250 and 500mg/kg body weight was selected and
administered orally before necrotizing agents. Antioxidant and antiulcer
parameters were evaluated and the stomach samples were subjected for
histopathological studies. In addition, PGE2 estimation and protein expressions
of COX-1, COX-2 and iNOS were analyzed by Western blot. The plant extract was
subjected to LCMS/MS analysis. In addition, Cytoprotective effect in isolated
gastric mucosal cells, TUNEL Assay, Acid neutralizing capacity assay, H+/K+
ATPase inhibitory assay were performed. RESULTS: The ulcer protection was found
to be 92%, 86% and 64% against ethanol, NSAID and pylorus ligation induced ulcer
respectively. The hydro-alcoholic extract of C. sappan heartwood exhibited
cytoprotective effect with 76.82% reduction against indomethacin-induced
cytotoxicity at the concentration of 25ug/ml. C. sappan showed 63.91% inhibition
in H+/K+ ATPase inhibitory assay at the concentration 500ug/ml. CONCLUSIONS: Our
results depict that Caesalpinia sappan heartwood possesses gastroprotective
activity, possibly mediated through cytoprotection and antioxidant mechanisms.
The data obtained in the present study provides scientific support for the
traditional use of Caesalpinia sappan in the management of peptic ulcer.
PMID- 27484931
TI - Ethnopharmacological study and topical anti-inflammatory activity of crude
extract from Poikilacanthus glandulosus (Nees) Ariza leaves.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological studies are important tools
as records and documentation of the empirical uses of medicinal plants in
traditional communities with the purpose of generating useful knowledge to lead
to the development of new medicines, biodiversity conservation and enhancement of
knowledge and local culture. Poikilacanthus glandulosus is widely used by the
population of City of Santiago, in Brazil, nevertheless, it does not have any
validation regarding its use and its medicinal effects. AIM: The objective of
this study was to perform one ethnopharmacological survey about P. glandulosus in
the City of Santiago and determine the anti-inflammatory activity in order to
prove its uses in popular medicine. METHODS: Personal and ethnopharmacological
data were collected through a prepared questionnaire. The phytochemical analysis
was performed observing the individual methodology for each reaction and by HPLC
UV. The antiedematogenic and anti-inflammatory (cell infiltration and
histological procedure) activities of the P. glandulosus (0.01-1000MUg/ear) were
evaluated in the ear edema model induced by topical application of croton oil.
RESULTS: P. glandulosus is known in City of Santiago as "Gaiana" and its
macerated leaves and branches are prepared with alcohol or sugarcane liquor
especially for insect bites, cicatrization and inflammation. HPLC analysis
revealed the presence of maslinic acid (2.024+/-0.10mg/g), uvaol (0.124+/
0.02mg/g) and sitosterol (0.502+/-0.05mg/g). The topical application of crude
extract of P. glandulosus reduced in a dose-dependent manner the croton oil
induced ear edema and myeloperoxidase activity (neutrophils infiltration marker)
with maximum inhibition of 87+/-2% and 64+/-12%, respectively at 1000ug/ear.
Dexamethasone (100ug/ear), used as a positive control, inhibited croton oil
induced ear edema in 89+/-3% and decreased myeloperoxidase activity in 50+/-3%.
Both P. glandulosus as dexamethasone reduced cell infiltration when evaluated by
histological procedure CONCLUSION: This work allowed us to understand the specie
P. glandulosus through ethnopharmacological study and it showed that the crude
extract presented antiedematogenic and anti-inflammatory actions, proving their
traditional use as anti-inflammatory.
PMID- 27484930
TI - Ethnopharmacology in the fight against Plasmodium parasites and brain disorders:
In memoriam of Philippe Rasoanaivo.
AB - Prof. Philippe Rasoanaivo was a highly dedicated and brilliant scientist in the
field of ethnopharmacology. He worked for the Institut Malgache de Recherches
Appliquees and the University of Antananarivo, Madagascar. His research was
mainly focused on the endemic medicinal and aromatic plants used by traditional
healers in Madagascar against a range of parasites, with special reference to
Plasmodium spp. In this Editorial, we resumed the key findings of his research
activity, with special reference to the discovery of alkaloids that markedly
enhance the action of chloroquine against malaria parasites.
PMID- 27484932
TI - Nitrate uptake varies with tide height and nutrient availability in the
intertidal seaweed Fucus vesiculosus.
AB - Intertidal seaweeds must cope with a suite of stressors imposed by aerial
exposure at low tide, including nutrient limitation due to emersion. Seaweeds can
access nutrients only when submerged, so individuals living higher compared to
lower on the shore may have adaptations allowing them to acquire sufficient
amounts of nutrients to survive and maintain growth. Using a combination of
observations and experiments, we aimed to identify intraspecific variation in
nitrate uptake rates across the intertidal distribution of F. vesiculosus, as
well as test for acclimation in response to a change in tide height. We
replicated our study at sites spanning nearly the entire Gulf of Maine coastline,
to examine how local environmental variability may alter intraspecific variation
in nitrate uptake. We found that average nitrate uptake rates were ~18% higher in
upper compared to lower intertidal Fucus vesiculosus. Furthermore, we found
evidence for both acclimation and adaptation to tide height during a transplant
experiment. F. vesiculosus transplanted from the lower to the upper intertidal
zone was characterized by increased nitrate uptake, but individuals transplanted
from the upper to the lower intertidal zone retained high uptake rates. Our
observations differed among Gulf of Maine regions and among time points of our
study. Importantly, these differences may reflect associations between nitrate
uptake rates and abiotic environmental conditions and seaweed nutrient status.
Our study highlights the importance of long-term variation in ambient nutrient
supply in driving intraspecific variation of seaweeds across the intertidal
gradient and local and seasonal variation in ambient nutrient levels in mediating
intraspecific differences.
PMID- 27484933
TI - Editorial: the burden of chronic liver disease - an ecological method sees the
wood for the trees.
PMID- 27484934
TI - Editorial: the burden of chronic liver disease - an ecological method sees the
wood for the trees. Authors' reply.
PMID- 27484935
TI - Editorial: dark chocolate may improve NAFLD and metabolic syndrome by reducing
oxidative stress.
PMID- 27484936
TI - Letter: clinical outcomes of HBsAg loss in chronic HBV infection.
PMID- 27484937
TI - Letter: clinical outcomes of HBsAg loss in chronic HBV infection - author's
reply.
PMID- 27484938
TI - Letter: long-term safety of nucleoside and nucleotide analogues in HBV
monoinfected patients.
PMID- 27484939
TI - Letter: long-term safety of nucleoside and nucleotide analogues in HBV
monoinfected patients - authors' reply.
PMID- 27484940
TI - Corrigendum.
PMID- 27484941
TI - Recurrent selection explains parallel evolution of genomic regions of high
relative but low absolute differentiation in a ring species.
AB - Recent technological developments allow investigation of the repeatability of
evolution at the genomic level. Such investigation is particularly powerful when
applied to a ring species, in which spatial variation represents changes during
the evolution of two species from one. We examined genomic variation among three
subspecies of the greenish warbler ring species, using genotypes at 13 013 950
nucleotide sites along a new greenish warbler consensus genome assembly. Genomic
regions of low within-group variation are remarkably consistent between the three
populations. These regions show high relative differentiation but low absolute
differentiation between populations. Comparisons with outgroup species show the
locations of these peaks of relative differentiation are not well explained by
phylogenetically conserved variation in recombination rates or selection. These
patterns are consistent with a model in which selection in an ancestral form has
reduced variation at some parts of the genome, and those same regions experience
recurrent selection that subsequently reduces variation within each subspecies.
The degree of heterogeneity in nucleotide diversity is greater than explained by
models of background selection, but is consistent with selective sweeps. Given
the evidence that greenish warblers have had both population differentiation for
a long period of time and periods of gene flow between those populations, we
propose that some genomic regions underwent selective sweeps over a broad
geographic area followed by within-population selection-induced reductions in
variation. An important implication of this 'sweep-before-differentiation' model
is that genomic regions of high relative differentiation may have moved among
populations more recently than other genomic regions.
PMID- 27484942
TI - SCAT3 assessment of non-head injured and head injured athletes competing in a
large international youth soccer tournament.
AB - To our knowledge, no study has evaluated Sideline Concussion Assessment Tool -3rd
Edition (SCAT3) scores during competition in athletes who have not had a head
injury. The purpose of our pilot study was to compare SCAT3 scores in non-injured
(NI), injured (but not head injured) (I), and head injured (HI) youth soccer
players during competition and to establish preliminary baseline data for non
head injured athletes in a competitive setting. The HI group demonstrated
significantly more symptoms (M = 9.7, SE = 0.8) than the I and NI (3.3, SE = 1.2,
and 3.2, SE = 0.7, respectively) groups. The HI group also demonstrated a
significantly higher symptom severity score (25.3, SE = 2.8) than the I and NI
groups (7.7, SE = 4.1, and 5.9, SE = 2.5, respectively). There were no
statistically significant differences in mean total Standardized Assessment of
Concussion (SAC) scores and mean subsection SAC scores between the groups.
Clinicians should also be aware that non-injured in-competition athletes may
report more symptoms on the SCAT3 than those evaluated in a non-competition
setting.
PMID- 27484943
TI - Stabilization of a Chiral Dirhodium Carbene by Encapsulation and a Discussion of
the Stereochemical Implications.
AB - For the first time, the stereochemical course of an asymmetric cyclopropanation
can be discussed on the basis of experimental structural information on a
pertinent chiral dirhodium carbene intermediate. Key to success was the formation
of racemic single crystals of a heterochiral [Rh2 {(S*)-PTTL}4 {=C(Ar)COOMe}][Rh2
{(R*)-PTTL}4 ] (Ar=MeOC6 H4 ; PTTL=N-phthaloyl-tert-leucinate) capsule, which has
been characterized by X-ray diffraction. NMR spectroscopic data confirm that the
obtained structural portrait is also relevant in solution and provide additional
information about the dynamics of this species. The chiral binding pocket is
primarily defined by the conformational preferences of the N-phthaloyl-protected
amino acid ligands and reinforced by a network of weak interligand interactions
that get stronger when chlorinated phthalimide residues are used.
PMID- 27484944
TI - Multiple regression analysis to assess the role of plankton on the distribution
and speciation of mercury in water of a contaminated lagoon.
AB - Spatial and seasonal variation of mercury species aqueous concentrations and
distributions was carried out during six sampling campaigns at four locations
within Laranjo Bay, the most mercury-contaminated area of the Aveiro Lagoon
(Portugal). Inorganic mercury (IHg(II)) and methylmercury (MeHg) were determined
in filter-retained (IHgPART, MeHgPART) and filtered (<0.45MUm) fractions
(IHg(II)DISS, MeHgDISS). The concentrations of IHgPART depended on site and on
dilution with downstream particles. Similar processes were evidenced for
MeHgPART, however, its concentrations increased for particles rich in phaeophytin
(Pha). The concentrations of MeHgDISS, and especially those of IHg(II)DISS,
increased with Pha concentrations in the water. Multiple regression models are
able to depict MeHgPART, IHg(II)DISS and MeHgDISS concentrations with salinity
and Pha concentrations exhibiting additive statistical effects and allowing
separation of possible addition and removal processes. A link between
phytoplankton/algae and consumers' grazing pressure in the contaminated area can
be involved to increase concentrations of IHg(II)DISS and MeHgPART. These
processes could lead to suspended particles enriched with MeHg and to the
enhancement of IHg(II) and MeHg availability in surface waters and higher
transfer to the food web.
PMID- 27484945
TI - Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis
of nuclear waste packages.
AB - A small scale sample nuclear waste package, consisting of a 28mm diameter uranium
penny encased in grout, was imaged by absorption contrast radiography using a
single pulse exposure from an X-ray source driven by a high-power laser. The
Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil,
in order to generate a bright burst of highly penetrating X-rays (with energy
>500keV), with a source size of <0.5mm. BAS-TR and BAS-SR image plates were used
for image capture, alongside a newly developed Thalium doped Caesium Iodide
scintillator-based detector coupled to CCD chips. The uranium penny was clearly
resolved to sub-mm accuracy over a 30cm(2) scan area from a single shot
acquisition. In addition, neutron generation was demonstrated in situ with the X
ray beam, with a single shot, thus demonstrating the potential for multi-modal
criticality testing of waste materials. This feasibility study successfully
demonstrated non-destructive radiography of encapsulated, high density, nuclear
material. With recent developments of high-power laser systems, to 10Hz
operation, a laser-driven multi-modal beamline for waste monitoring applications
is envisioned.
PMID- 27484946
TI - Comparative metagenomic analysis of PAH degradation in soil by a mixed microbial
consortium.
AB - In this study, we used a taxonomic and functional metagenomic approach to analyze
some of the effects (e.g. displacement, permanence, disappearance) produced
between native microbiota and a previously constructed Polycyclic Aromatic
Hydrocarbon (PAH)-degrading microbial consortium during the bioremediation
process of a soil polluted with PAHs. Bioaugmentation with a fungal-bacterial
consortium and biostimulation of native microbiota using corn stover as
texturizer produced appreciable changes in the microbial diversity of polluted
soils, shifting native microbial communities in favor of degrading specific
populations. Functional metagenomics showed changes in gene abundance suggesting
a bias towards aromatic hydrocarbon and intermediary degradation pathways, which
greatly favored PAH mineralization. In contrast, pathways favoring the formation
of toxic intermediates such as cytochrome P450-mediated reactions were found to
be significantly reduced in bioaugmented soils. PAH biodegradation in soil using
the microbial consortium was faster and reached higher degradation values (84%
after 30 d) as a result of an increased co-metabolic degradation when compared
with other mixed microbial consortia. The main differences between inoculated and
non-inoculated soils were observed in aromatic ring-hydroxylating dioxygenases,
laccase, protocatechuate, salicylate and benzoate-degrading enzyme genes. Based
on our results, we propose that several concurrent metabolic pathways are taking
place in soils during PAH degradation.
PMID- 27484947
TI - Oil removal of spent hydrotreating catalyst CoMo/Al2O3 via a facile method with
enhanced metal recovery.
AB - Deoiling process is a key issue for recovering metal values from spent
hydrotreating catalysts. The oils can be removed with organic solvents, but the
industrialized application of this method is greatly hampered by the high cost
and complex processes. Despite the roasting method is simple and low-cost, it
generates hardest-to-recycle impurities (CoMoO4 or NiMoO4) and enormous toxic
gases. In this study, a novel and facile approach to remove oils from the spent
hydrotreating catalysts is developed. Firstly, surface properties of spent
catalysts are characterized to reveal the possibility of oil removal. And then,
oils are removed with water solution under the conditions of 90 degrees C, 0.1wt%
SDS, 2.0wt% NaOH and 10ml/gL/S ratio for 4h. Finally, thermal treatment and
leaching tests are carried out to further explore the advantages of oil removal.
The results show that no hardest-to-recycle impurity CoMoO4 is found in XPS
spectra of thermally treated samples after deoiling and molybdenum is leached
completely with sodium carbonate solution. It means that the proposed deoiling
method can not only remove oils simply and without enormous harmful gases
generating, but also avoid the generation of detrimental impurity and promote
recycling of valuable metals from spent hydrotreating catalysts.
PMID- 27484948
TI - Rice ingestion is a major pathway for human exposure to organophosphate flame
retardants (OPFRs) in China.
AB - Although organophosphate flame retardants (OPFRs) have been shown to accumulate
in abiotic and biotic environmental compartments, data about OPFRs concentrations
in various foods are limited and are none in humans through diets. In this work,
the concentrations of 6 typical OPFRs were investigated in 50 rice samples, 75
commonly consumed foods and 45 human hair samples from China. The dietary intakes
of OPFRs for adult people via food ingestion were estimated. The concentrations
of SigmaOPFRs in foods ranged from 0.004ng/g to 287ng/g. OPFRs were detected in
53.3% of the human hair samples. The highest OPFRs concentrations were found in
rice and vegetables. Tri(2-chloroethyl)phosphate(TCEP), tris(2
chloroisopropyl)phosphate(TCIPP), and tri(2-ethyltexyl)phosphate(TEHP) were
predominant in all food samples. OPFRs concentrations in foods were not
significantly affected by the packaging materials. The mean dietary intakes of
SigmaOPFRs for adult males and females were 539 and 601ng/kg body weight/day,
respectively. The greatest contribution to these values is from rice, accounting
for approximately 60% of the total intake, particularly from rice protein. Rice
ingestion was considered a potential major pathway for human exposure to OPFRs,
and regional differences in the levels of OPFRs in foods and dietary differences
should be given more attention in the future.
PMID- 27484950
TI - Strong, healthy, energized: Striving for a healthy weight in an older lesbian
population.
AB - The Office on Women's Health funded five pilot healthy weight intervention
studies for lesbian and bisexual (LB) women, which included a program called
Strong. Healthy. Energized (SHE). SHE was a 12-session program, targeted toward
LB women age 60 and older, which focused on exercise, including a pedometer to
track steps; nutrition; stress management; and group discussions. The program
enrolled 39 participants. Waist circumference decreased by 3.7% across the group
(p < .01). Participants with the lowest one-third baseline step count saw a
marked step increase. This intervention was effective in improving health
behaviors and short-term health outcomes for older LB women.
PMID- 27484951
TI - New family of biosensors for monitoring BTX in aquatic and edaphic environments.
AB - Benzene, toluene, ethylbenzene and xylenes (BTEX) contamination is a serious
threat to public health and the environment, and therefore, there is an urgent
need to detect its presence in nature. The use of whole-cell reporters is an
efficient, easy-to-use and low-cost approach to detect and follow contaminants
outside specialized laboratories; this is especially important in oil spills that
are frequent in marine environments. The aim of this study is the construction of
a bioreporter system and its comparison and validation for the specific detection
of monocyclic aromatic hydrocarbons in different host bacteria and environmental
samples. Our bioreporter system is based on the two component regulatory system
TodS-TodT of P. putida DOT-T1E, and the PtodX promoter fused to the GFP protein
as the reporter protein. For the construction of different biosensors, this
bioreporter was transferred into three different bacterial strains isolated from
three different environments, and their performance was measured. Validation of
the biosensors on water samples spiked with petrol, diesel and crude oil on
contaminated waters from oil spills and on contaminated soils demonstrated that
they can be used in mapping and monitoring some BTEX compounds (specifically
benzene, toluene and two xylene isomers). Validation of biosensors is an
important issue for the integration of these devices into pollution-control
programmes.
PMID- 27484949
TI - microRNA-132/212 deficiency enhances Abeta production and senile plaque
deposition in Alzheimer's disease triple transgenic mice.
AB - The abnormal regulation of amyloid-beta (Abeta) metabolism (e.g., production,
cleavage, clearance) plays a central role in Alzheimer's disease (AD). Among
endogenous factors believed to participate in AD progression are the small
regulatory non-coding microRNAs (miRs). In particular, the miR-132/212 cluster is
severely reduced in the AD brain. In previous studies we have shown that miR
132/212 deficiency in mice leads to impaired memory and enhanced Tau pathology as
seen in AD patients. Here we demonstrate that the genetic deletion of miR-132/212
promotes Abeta production and amyloid (senile) plaque formation in triple
transgenic AD (3xTg-AD) mice. Using RNA-Seq and bioinformatics, we identified
genes of the miR-132/212 network with documented roles in the regulation of Abeta
metabolism, including Tau, Mapk, and Sirt1. Consistent with these findings, we
show that the modulation of miR-132, or its target Sirt1, can directly regulate
Abeta production in cells. Finally, both miR-132 and Sirt1 levels correlated with
Abeta load in humans. Overall, our results support the hypothesis that the miR
132/212 network, including Sirt1 and likely other target genes, contributes to
abnormal Abeta metabolism and senile plaque deposition in AD. This study
strengthens the importance of miR-dependent networks in neurodegenerative
disorders, and opens the door to multifactorial drug targets of AD by targeting
Abeta and Tau.
PMID- 27484952
TI - REM sleep behavior disorder was associated with Parkinson's disease: a community
based study.
AB - BACKGROUND: Our study was aimed to validate a modified RBD (REM sleep behavior
disorder) single question (RBD1Q-C), study the prevalence of probable RBD (pRBD)
in a rural community based on RBD1Q-C and investigate the association between
pRBD and Parkinson's disease (PD). METHODS: The validation study of RBD1Q-C
included 32 Chinese participants (14 idiopathic RBD patients and 18 controls).
All participants underwent a polysomnogram (PSG). We then conducted a door-to
door survey to estimate the prevalence of pRBD assessed by RBD1Q-C, and its
association with PD among 19614 residents who lived in Malu community of
Shanghai, China. RESULTS: RBD1Q-C demonstrated a high sensitivity of 100%, a
moderate specificity of 55.6%. The agreement between RBD1Q-C and PSG-based RBD
diagnosis was good (k = 0.552). PPV of the RBD1Q-C was 63.6% and NPV was 100%.
The prevalence of pRBD in Malu community was 4.9%. In people over 50 years old,
presence of pRBD was significantly associated with increased risk of having PD
(odds ratio = 2.61, 95% CI: 1.56-4.39). CONCLUSION: RBD1Q-C was shown to be a
useful screening tool. Based on the RBD1Q-C, we found that pRBD was not rare in
Chinese rural population and associated with odds of PD, calling for more
attention from patients, caregivers and physicians.
PMID- 27484953
TI - Microhardness of human cancellous bone tissue in progressive hip osteoarthritis.
AB - Bone tissue is a biological system in which the dynamic processes of, among
others, bone formation or internal reconstruction will determine the spatial
structure of the tissue and its mechanical properties. The appearance of a factor
disturbing the balance between biological processes, e.g. a disease, will cause
changes in the spatial structure of bones, thus affecting its mechanical
properties. One of the bone diseases most common in an increasingly ageing
population is osteoarthritis, also referred to as degenerative joint disease. It
is estimated that in 2050 about 1300 million people will show symptoms of OA. The
appearance of a pathological stimulus disturbs the balance of the processes of
degradation and synthesis of articular cartilage, chondrocytes and the
extracellular matrix, and the subchondral bone layer. As osteoarthritis
progresses, study of the epiphysis reveals increasingly widespread changes of the
articular surface and the internal structure of bone tissue. In this paper, the
authors point out the differences in the mechanical properties of cancellous bone
tissue forming the proximal epiphysis of the femoral bone during the progressive
stages of OA. In order to determine microproperties of bone trabeculae, specimens
from different stages of the disease (N=9) were subjected to microindentation
testing, which made it possible to determine the material properties of bone
tissue, such as microhardness HV and Young's modulus E. In addition, mechanical
tests were supplemented with Raman spectroscopy, which determine the degree of
bone mineralization, and measurements of structural properties based on analysis
using microCT. The conducted tests were used to establish both quantitative and
quantitative description of changes in the structural and mechanical properties
connected with reorganization of trabeculae making up the bone in the various
stages of osteoarthritis. The proposed description will supplement existing
knowledge in the literature about identification of the processes occurring
during the development of this disease.
PMID- 27484954
TI - A simultaneous diagnosis and genotyping method for global surveillance of
cetacean morbillivirus.
AB - Cetacean morbillivirus (CeMV) is considered one of the most important viral
pathogens in cetaceans. CeMV outbreaks of lethal disease have repeatedly been
observed in Europe, the Americas, and Australia, while large herds of gregarious
species were found to be the likely reservoirs and sources of CeMV infection to
susceptible species in the Atlantic and Pacific Oceans. Furthermore, three new
strains were detected recently in Hawaii, Brazil and Australia. To clarify the
real global distribution of CeMV and possible carriers, we showed a novel
technique successfully diagnosing and distinguishing different virus strains
(DMV, PWMV and novel CeMVs) using FFPE samples from 1996 to 2011. This efficient
method that combines qRT-PCR and high resolution melting (HRM) could be applied
to the future retrospective global studies for better understanding of different
prevalence and outbreak conditions among ocean basins and the mechanism of
variable host response to pathogens.
PMID- 27484956
TI - Detecting hepatitis B virus in surgical smoke emitted during laparoscopic
surgery.
AB - BACKGROUND: Hepatitis B virus (HBV) transmission is known to occur through direct
contact with infected blood. There has been some suspicion that the virus can
also be detected in aerosol form. However, this has never been directly shown.
The purpose of this study was to sample and analyse surgical smoke from
laparoscopic surgeries on patients with hepatitis B to determine whether HBV is
present. METHODS: A total of 11 patients who underwent laparoscopic or robotic
abdominal surgeries between October 2014 and February 2015 at Korea University
Anam Hospital were included in this study. A high efficiency collector was used
to obtain surgical smoke in the form of hydrosol. The smoke was analysed by using
nested PCR. RESULTS: Robotic or laparoscopic colorectal resections were performed
in 5 cases, laparoscopic gastrectomies in 3 cases and laparoscopic hepatic wedge
resections in another 3 cases. Preoperatively, all of the patients had positive
hepatitis B surface antigen (HBsAg). 2 patients had detectable HBsAb, and 2 were
positive for hepatitis B e antigen. 3 patients were taking antihepatitis B viral
medications at the time of the study. The viral load measured in the patients'
blood was undetectable to 1.7*108 IU/mL. HBV was detected in surgical smoke in 10
of the 11 cases. CONCLUSIONS: HBV is detectable in surgical smoke. This study
provides preliminary data in the investigation of airborne HBV infection.
PMID- 27484955
TI - Risk of renal cell carcinoma following exposure to metalworking fluids among
autoworkers.
AB - OBJECTIVES: Metalworking fluids (MWF), used to cool and lubricate metal in
occupational settings, are linked to several cancers but data on kidney cancer
are limited. We examine how MWF influence the rate of renal cell carcinoma (RCC)
in a large prospective study. METHODS: A cohort of Michigan autoworkers
consisting of 33 421 individuals was followed from 1985 to 2009. The cohort was
linked to the Michigan Cancer Registry to identify new cases of RCC. We analysed
RCC in relation to cumulative exposure to each specific type of MWF (straight,
soluble and synthetic) and all 3 types pooled into a single MWF variable, with a
15-year lag. Cox proportional hazards regression with splines were used to
estimate hazard ratios (HRs) and 95% confidence intervals (CIs), controlling for
age, gender, race, calendar year, year hired, time since hire, plant and other
MWF types. RESULTS: There were 135 incident cases. A linear increase in the log
HR was observed for RCC with increasing cumulative exposure to each MWF type and
total MWF exposure. At the mean of total MWF exposure (18.80 mg/m(3)-year), the
estimated HR was 1.11 (95% CI 1.04 to 1.19). CONCLUSIONS: Our results provide
evidence for a dose-dependent association between MWF exposure and RCC. The
influence of components of oil-based and water-based MWF needs further
examination.
PMID- 27484958
TI - Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in
ultraviolet B-irradiated hairless mice.
AB - We investigated whether cilostazol, an activator of cyclic adenosine
monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet
B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol
decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as
increased staining of collagen fibers and inhibition of reactive oxygen species
(ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase
matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly
decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed
that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and
nuclear factor (NF)-kappaB was significantly inhibited by cilostazol, whereas the
activation of Akt was significantly enhanced by cilostazol. Confirmation of
localized protein expression in the skin revealed marked p38 MAPK and NF-kappaB
activation that was mainly detected in the dermis. Marked Akt activation was
mainly detected in the epidermis. Our results suggest that cilostazol may have
anti-photoaging effects on UVB-induced wrinkle formation by maintaining the
extracellular matrix density in the dermis, which occurs via regulation of ROS
and related p38 MAPK and NF-kappaB signaling, and subsequent down-regulation of
MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle
formation.
PMID- 27484959
TI - Modulation of type 1 and type 2 diabetes risk by the intestinal microbiome.
AB - The prevalence of type 1 and type 2 diabetes have both risen dramatically over
the last 50 years. Recent findings point towards the gut microbiota as a
potential contributor to these trends. The hundred trillion bacteria residing in
the mammalian gut have established a symbiotic relation with their host and
influence many aspects of host metabolism, physiology, and immunity. In this
review, we examine recent data linking gut microbiome composition and function to
anti-pancreatic immunity, insulin-resistance, and obesity. Studies in rodents and
human longitudinal studies suggest that an altered gut microbiome characterized
by lower diversity and resilience is associated with type 1 and type 2 diabetes.
Through its metabolites and enzymatic arsenal, the microbiota shape host
metabolism, energy extracted from the diet and contribute to the normal
development of the immune system and to tissue inflammation. Increasing evidence
underscores the importance of the maternal microbiome, the gestational
environment and the conditions of newborn delivery in establishing the gut
microbiota of the offspring. Perturbations of the maternal microbiome during
gestation, or that of the offspring during early infant development may promote a
pro-inflammatory environment conducive to the development of autoimmunity and
metabolic disturbance. Collectively the findings reviewed herein underscore the
need for mechanistic investigations in rodent models and in human studies to
better define the relationships between microbial and host inflammatory activity
in diabetes, and to evaluate the potential of microbe-derived therapeutics in the
prevention and treatment of both forms of diabetes.
PMID- 27484957
TI - Noninvasive early detection of anthracycline-induced cardiotoxicity in patients
with hematologic malignancies using the phased tracking method.
AB - Anthracyclines are among the most effective and widely used anticancer drugs;
however, their use is limited by serious cardiotoxicity. Early detection is
necessary to prevent the high mortality rate associated with heart failure (HF).
We evaluated cardiac function in 142 patients using conventional echocardiography
and the phased tracking method (PTM), which was measured using the minute
vibration and the rapid motion components, neither of which is recognized in
standard M-mode nor in tissue Doppler imaging. For systolic function comparison,
we compared left ventricular ejection fraction (LVEF) in conventional
echocardiography with the average velocity of ventricular septum myocytes (Vave )
in the PTM. The Vave of 12 healthy volunteers was 1.5 (m/s)/m or more. At
baseline of 99 patients, there was a positive correlation between LVEF and Vave
in all patients. There were no significant differences in baseline cardiac
function between patients with and without HF. There was a negative correlation
between the cumulative anthracycline dose and LVEF or Vave among all patients. We
determined that Vave 1.5 (m/s)/m was equivalent to LVEF 60%, 1.25 (m/s)/m to 55%,
and 1.0 (m/s)/m to 50%. During the follow-up period, there was a pathological
decrease in LVEF (<55%) and Vave (<1.25 m/s/m) in patients with HF; decreases in
Vave were detected significantly earlier than those in LVEF (P < 0.001). When
Vave declined to 1.5 (m/s)/m or less, careful continuous observation and cardiac
examination was required. When Vave further declined to 1.0 (m/s)/m or lower,
chemotherapy was postponed or discontinued; thus, serious drug-induced
cardiomyopathy was avoided in patients who did not relapse. The PTM was superior
to echocardiography for early, noninvasive detection and intermediate-term
monitoring of left ventricle systolic function associated with anthracycline
chemotherapy, among patients with hematologic malignancies. The PTM was an
effective laboratory procedure to avoid the progression to serious
cardiomyopathy.
PMID- 27484960
TI - The ALPPS procedure for hepatocellular carcinoma larger than 10 centimeters.
AB - INTRODUCTION: The only means of achieving long-term survival in hepatocellular
carcinoma is complete tumor resection or liver transplantation. Patients with
large hepatocellular carcinomas are currently not considered for liver
transplantation. Associating liver partition and portal vein ligation for staged
hepatectomy (ALPPS) is indicated in selected patients. We present the case of a
patient with a huge hepatocellular carcinoma who underwent an ALPPS procedure.
PRESENTATION OF CASE: A 57-year-old man initially presented with a tumor
measuring 19cm*10cm in the right lobe of the liver. The liver function was normal
and there was no evidence of portal hypertension. The first part of the procedure
was performed without mobilizing the liver. The middle hepatic vein was divided
during parenchymal transection. The second procedure was performed after 15days.
During that procedure the right hepatic artery, right bile duct, and the right
hepatic vein were ligated and divided. Liver segments 4-8 with the tumor were
removed. The patient developed moderate ascites but recovered after ten days.
After 90days, the patient is doing well with no signs of recurrence. DISCUSSION:
Hepatocellular carcinoma is a complicated disease and ALPPS is not considered an
optimal treatment option. However, patients with large tumors are not considered
for liver transplantation or chemotherapy. Patients with Child-Pugh A liver
disease without portal hypertension can benefit from surgical treatment for
hepatocellular carcinoma; in some situations, surgery may be considerably better
than other forms of treatment. CONCLUSION: ALPPS should be considered in selected
patients with large hepatocellular carcinomas.
PMID- 27484961
TI - Methods for investigating the local spatial anisotropy and the preferred
orientation of cones in adaptive optics retinal images.
AB - The ability to noninvasively image the cone photoreceptor mosaic holds
significant potential as a diagnostic for retinal disease. Central to the
realization of this potential is the development of sensitive metrics for
characterizing the organization of the mosaic. Here we evaluated previously
described and newly-developed (Fourier- and Radon-based) methods of measuring
cone orientation in simulated and real images of the parafoveal cone mosaic. The
proposed algorithms correlated well across both simulated and real mosaics,
suggesting that each algorithm provides an accurate description of photoreceptor
orientation. Despite high agreement between algorithms, each performed
differently in response to image intensity variation and cone coordinate jitter.
The integration property of the Fourier transform allowed the Fourier-based
method to be resistant to cone coordinate jitter and perform the most robustly of
all three algorithms. Conversely, when there is good image quality but unreliable
cone identification, the Radon algorithm performed best. Finally, in cases where
the cone coordinate reliability was excellent, the method previously described by
Pum and colleagues performed best. These descriptors are complementary to
conventional descriptive metrics of the cone mosaic, such as cell density and
spacing, and have the potential to aid in the detection of photoreceptor
pathology.
PMID- 27484962
TI - Fractalkine/CX3CL1 in rheumatoid arthritis.
AB - Fractalkine is a CX3C chemokine that exists in both membrane-bound and soluble
forms. Interaction between fractalkine and its unique receptor (CX3CR1) induces
cell adhesion, chemotaxis, crawling, "accessory cell" activity, and survival. The
serum level of fractalkine is elevated in patients with rheumatoid arthritis (RA)
and is correlated with disease activity. Peripheral blood CD16+ monocytes and a
subset of T cells express CX3CR1, while fractalkine is expressed on fibroblast
like synoviocytes and endothelial cells in the synovial tissue of patients with
RA. Fractalkine expression is enhanced by tumor necrosis factor-alpha and
interferon-gamma, and it promotes the migration of monocytes, T cells, and
osteoclast precursors into RA synovial tissue. Fractalkine also induces the
production of inflammatory mediators by macrophages, T cells, and fibroblast-like
synoviocytes. Moreover, fractalkine promotes angiogenesis and osteoclastogenesis.
In an animal model of RA, arthritis was improved by the abrogation of
fractalkine. Recently, a clinical trial of an anti-fractalkine monoclonal
antibody for the treatment of RA commenced in Japan. We review the multiple roles
of fractalkine in the pathogenesis of RA and its potential as a therapeutic
target for this disease.
PMID- 27484963
TI - Aging of the endocrine system and its potential impact on sarcopenia.
AB - Sarcopenia, occurring as a primary consequence of aging, is a progressive
generalized decline of skeletal muscle mass, strength and function. The
pathophysiology of sarcopenia is complex and multifactorial. One major cause of
muscle mass and strength loss with aging appears to be the alteration in hormonal
networks involved in the inflammatory processes, muscle regeneration and protein
synthesis. This review describes the recent findings concerning the role of the
aging on the endocrine system in the development of sarcopenia. We also report
the benefits and safety of hormone replacement therapy in elderly subjects and
discuss future perspectives in the therapy and prevention of skeletal muscle
aging.
PMID- 27484964
TI - Fetal cerebral and umbilical Doppler in pregnancies complicated by late-onset
placental abruption.
AB - OBJECTIVE: To evaluate whether changes in the cerebroplacental Doppler and birth
weight (BW) suggestive of chronic fetal hypoxemia, precede the development of
late-onset placental abruption (PA) after 32 weeks. METHODS: In a multicenter
retrospective study, the Doppler examinations of the fetal umbilical artery (UA)
and middle cerebral artery (MCA) recorded after 32 weeks were collected in
pregnancies subsequently developing PA. The BW centiles were calculated and the
MCA pulsatility indices (PI), and UA PI were converted into multiples of the
median (MoM). Afterwards, a comparison was made with a group of fetuses, which
did not develop PA. Logistic regression was used to adjust for potential
confounders and evaluate the feasibility of the prediction model. RESULTS:
Pregnancies complicated by late-onset PA (n = 31) presented lower MCA PI (p =
0.015) and were smaller (p < 0.001) than those who did not (n = 1294). Logistic
regression analysis indicated that cerebral vasodilation was more important than
umbilical flow in the explanation of PA (MCA PI OR = 0.106, p = 0.014 and UA PI
OR 1.901, p = 0.32). In addition, the influence of BW exerted was residual (BW
centile OR = 0.989, p = 0.15). CONCLUSIONS: Fetuses developing late-onset PA
demonstrate significant cerebral vasodilation with scarce placental dysfunction,
suggesting the existence of some kind of chronic hypoxemia that follows the late
onset pattern.
PMID- 27484965
TI - Repetitive thinking, executive functioning, and depressive mood in the elderly.
AB - OBJECTIVES: Previous findings and the depressive-executive dysfunction hypothesis
suggest that the established association between executive functioning and
depression is accounted for by repetitive thinking. Investigating the association
between executive functioning, repetitive thinking, and depressive mood, the
present study empirically tested this mediational model in a sample of older
adults, while focusing on both concrete and abstract repetitive thinking. This
latter distinction is important given the potential protective role of concrete
repetitive thinking, in contrast to the depletive effect of abstract repetitive
thinking. METHOD: A sample of 43 elderly volunteers, between 75 and 95 years of
age, completed tests of executive functioning (the Stroop test, the Trail Making
test, and the Fluency test), and questionnaires of repetitive thinking and
depression. RESULTS: Positive correlations were observed between abstract
repetitive thinking and depressive mood, and between concrete repetitive thinking
and executive functioning; a negative correlation was observed between depressive
mood and executive functioning. Further, mediational analysis evidenced that the
relation between executive functioning and depressive mood was mediated by
abstract repetitive thinking. CONCLUSION: The present data provide, for the first
time, empirical support to the depressive-executive dysfunction hypothesis: the
lack of executive resources would favor a mode of abstract repetitive thinking,
which in turn would deplete mood. It suggests that clinical intervention
targeting depression in the elderly should take into consideration repetitive
thinking modes and the executive resources needed to disengage from rumination.
PMID- 27484966
TI - Exploring the interaction between picoplatin and human serum albumin: The effects
on protein structure and activity.
AB - For the first time, the effects of picoplatin on the structure and esterase-like
catalytic activity of human serum albumin (HSA) have been investigated by
spectroscopic approaches and molecular modeling. The circular dichroism (CD)
spectral examinations indicated that the binding of picoplatin with HSA induced a
slight decrease of a-helix content of protein and unfolded the constituent
polypeptides of the protein. The synchronous fluorescence and three-dimensional
fluorescence spectral methods were used to estimate the effect of picoplatin on
the micro-environmental changes of the Trp and Tyr residues of HSA, indicating
that the micro-environment around the Tyr and Trp residue is partly disturbed by
picoplatin. UV-vis absorption spectral result indicated the formation of the
ground state complex between picoplatin with HSA. The ANS binding assay indicated
the existence of competitive combination of picoplatin and ANS with HSA. The
studies on the effects of picoplatin on the binding of HSA with bilirubin and
heme showed that picoplatin binding caused a change of angle between two
chromophores of bound bilirubin and the binding site of picoplatin does not
locate in subdomain IB in HSA that bound with heme. The molecular modeling
results showed that picoplatin binds to the connection between domain I and
domain II by hydrophobic, hydrogen bonds, and van der Waals forces. In addition,
HSA maintains most of its esterase activity in the presence of picoplatin. The
investigations on how picoplatin interacts with HSA are important for the
understanding of the anticancer mechanism and toxicity of platinum-based
anticancer drug.
PMID- 27484967
TI - Adjusting irradiance to enhance growth and lipid production of Chlorella vulgaris
cultivated with monosodium glutamate wastewater.
AB - Light is one of the most important factors affecting microalgae growth and
biochemical composition. The influence of illumination on Chlorella vulgaris
cultivated with diluted monosodium glutamate wastewater (MSGW) was investigated.
Six progressive illumination intensities (0, 30, 90, 150, 200 and 300MUmol.m(
2)s(-1)), were used for C. vulgaris cultivation at 25 degrees C. Under
150MUmol.m(-2)s(-1), the corresponding specific light intensity of 750*10(
6)MUmol.m(-2)s(-1) per cell, algae obtained the maximum biomass concentration
(1.46g.L(-1)) on the 7th day, which was 3.5 times of that under 0MUmol.m(-2)s(
1), and the greatest average specific growth rate (0.79 d(-1)) in the first
7days. The results showed the importance role of light in mixotrophic growth of
C. vulgaris. High light intensities of 200 and 300MUmol.m(-2)s(-1) would inhibit
microalgae growth to a certain degree. The algal lipid content was the greatest
(30.5%) at 150MUmol.m(-2)s(-1) light intensity, which was 2.42 times as high as
that cultured in dark. The protein content of C. vulgaris decreased at high light
intensities of 200 and 300MUmol.m(-2)s(-1). The effect of irradiance on
carbohydrate content was inversely correlated with that on protein. The available
light at an appropriate intensity, not higher than 200MUmol.m(-2)s(-1), was
feasible for economical cultivation of C. vulgaris in MSGW.
PMID- 27484968
TI - An erythematous palmoplantar rash due to human parechovirus.
PMID- 27484969
TI - Developing, implementing and evaluating integrated care models for infants,
children, young people and their families.
PMID- 27484970
TI - New patient-reported experience measure for children with allergic disease:
development, validation and results from integrated care.
AB - OBJECTIVES: To develop and validate a new allergy-specific patient-reported
experience measure (PREM) for children and their parents, and to collect feedback
in an integrated care setting. DESIGN: Two allergy-specific PREMs were produced
using focus groups, cognitive testing, two prospective validation studies
(collaboration: Royal College of Paediatrics and Child Health, Picker Institute
Europe, Imperial College/London): 'Your Allergy Care', for children aged 8-16
years; 'Your Child's Allergy Care', for parents of children aged 0-7 years.
SETTING: Community event, primary/secondary/tertiary allergy care settings. MAIN
OUTCOME MEASURES: Performance of PREMs in validation study; reported experience
of allergy care. PARTICIPANTS: 687 children with allergic conditions and their
parents/carers. RESULTS: In total, 687 questionnaires were completed; 503/687
(253 child; 250 parent) for the final survey. In both surveys, demographic
variations were not associated with differences in results. Although 71% of
patients reported one or more allergic conditions (food allergy/eczema/hay
fever/asthma), 62% required multiple visits before receiving final diagnosis.
Overall, patient experience was good for communication with patient/parent,
competence and confidence in ability, and 73% felt looked after 'very well' and
23% 'quite well'. Areas for improvement included communication with
nurseries/schools, more information on side effects, allergic conditions and
allergen/irritant avoidance. Allergy care in primary/emergency care settings was
associated with higher problem-scores (worse experience) than in specialist
clinics. CONCLUSIONS: These new PREMs will allow allergy-specific patient
experience reporting for children and parents and help identification of priority
areas for improvement and commissioning of care. Efforts towards better allergy
care provision must be targeted at primary and emergency care settings and
underpinned by improving communication between healthcare providers and the
community.
PMID- 27484971
TI - Outcome of adenotonsillectomy in children with Down syndrome and obstructive
sleep apnoea.
AB - OBJECTIVE: To evaluate the outcome of adenotonsillectomy (AT) in a cohort of
children with Down syndrome (DS) and obstructive sleep apnoea (OSA). DESIGN:
Retrospective, cross-sectional study. SETTING: Tertiary care centre. PATIENTS:
Children with DS and OSA, without previous upper airway (UA) surgery.
INTERVENTIONS: AT and full overnight polysomnography. MAIN OUTCOME RESULTS: A
significant improvement of the obstructive apnoea-hypopnoea index (oAHI) after AT
was obtained. No differences in sleep efficiency or sleep fragmentation were
found postoperatively. Almost half of the children had persistent OSA (oAHI
>=5/hour). RESULTS: Data are presented as median (lower-upper quartile). Thirty
four children were included, median age 4.0 years (2.7-5.8), body mass index
(BMI) z-score 0.81 (-0.46-1.76), and oAHI 11.4/hour (6.5-22.7). The majority
presented with severe OSA (58.9%). AT was performed in 22 children, tonsillectomy
in 10 and adenoidectomy in two. Postoperatively, a significant improvement of the
oAHI was measured from 11.4/hour (6.5-22.7) to 3.6/hour (2.1-9.5) (p=0.001), with
a parallel increase of the minimum oxygen saturation (p=0.008). Children with
initially more severe OSA had significantly more improvement after UA surgery
(p=0.001). Persistent OSA was found in 47.1% of the children. CONCLUSIONS: AT
results in a significant improvement of OSA in children with DS without a change
in sleep efficiency or sleep stage distribution. Severe OSA was associated with a
larger reduction of OSA severity. Almost half of the children had persistent OSA,
which was not correlated to age, gender or BMI z-score.
PMID- 27484972
TI - Hemodynamics through the congenitally bicuspid aortic valve: a computational
fluid dynamics comparison of opening orifice area and leaflet orientation.
AB - A computational fluid dynamics model of a bicuspid aortic valve has been
developed using idealised three-dimensional geometry. The aim was to compare how
the orifice area and leaflet orientation affect the hemodynamics of a pure
bicuspid valve. By applying physiologic material properties and boundary
conditions, blood flow shear stresses were predicted during peak systole. A
reduced orifice area altered blood velocity, the pressure drop across the valve
and the wall shear stress through the valve. Bicuspid models predicted impaired
blood flow similar to a stenotic valve, but the flow patterns were specific to
leaflet orientation. Flow patterns developed in bicuspid aortic valves, such as
helical flow, were sensitive to cusp orientation. In conclusion, the reduced
opening area of a bicuspid aortic valve amplifies any impaired hemodynamics, but
cusp orientation determines subsequent flow patterns which may determine the
specific regions downstream from the valve most at risk of clinical
complications.
PMID- 27484973
TI - Preoperative hemoglobin level: the best predictor of transfusion of packed red
cells.
AB - Blood transfusions could have serious consequences for patients. A reduction in
the transfusion rate could be accomplished by an optimized blood management.
Clear guidelines and awareness among all employees at a single institution have
resulted in a reduction in transfusion rates in recent years. Identification of
the group of patients who still received a blood transfusion in recent years
could result in a further reduction. This study enrolled 4022 patients undergoing
cardiothoracic surgery between 2008 and 2013. Patients were divided into three
groups: "no blood transfusion", "transfusion of packed red cells only" and "any
other combinations of blood transfusion". In total, 16 variables were tested for
their association with the administration of homologous blood. The variables
associated with blood transfusion were included in a stepwise multinomial
logistic regression analysis to find the variables with the strongest
association.For the transfusion of packed red cells only and any other
combinations of blood transfusion, the following predictors are found: gender,
age, weight, type of surgery, reoperation, unstable angina pectoris,
endocarditis, recent myocardial infarction, preoperative creatinine level,
preoperative hemoglobin level and preoperative platelet count. The best predictor
for the transfusion of packed red cells is preoperative hemoglobin level (4.1 to
7.8 mmol/l). For other blood products, the strongest association was found with
type of surgery (aortic surgery, ventricular septal rupture and intracardiac
tumour).
PMID- 27484974
TI - Cross-talk between the dipeptidyl peptidase-4 and stromal cell-derived factor-1
in stem cell homing and myocardial repair: Potential impact of dipeptidyl
peptidase-4 inhibitors.
AB - Dipeptidyl peptidase-4 (DPP-4), glycyl-prolyl-naphthylamidase, is a serine
protease that catalyzes the hydrolysis of various proline-containing
polypeptides. It is involved in the inactivation of glucagon-like peptide-1 (GLP
1) and glucose-dependent insulinotropic polypeptide (GIP), having in this way a
profound influence on glucose metabolism. During organ damage, stromal and
endothelial cells produce a chemokine known as stromal cell-derived factor-1 (SDF
1), a powerful chemoattractant of stem/progenitor cells. SDF-1 binds to a
specific alpha-chemokine receptor (CXCR4) and can be degraded by proteases,
including matrix DPP-4/CD26, presented in the circulation, or activated in
injured tissues. DPP-4 inhibition has received considerable attention because of
its significant therapeutic benefits in the regulation of insulin secretion and
tissue insulin sensitivity, the regulation of tumor growth and metastasis,
angiogenesis, tissue repair, especially after myocardial infarction, and
regulation of endocrine function. Inhibition of circulating proteases appears to
maintain the optimal endogenous SDF-1 concentration and may enhance homing of
endothelial progenitor cells. In the present article, we present an overview of
some basic facts about the role of DPP-4 in glucose homeostasis, the mechanism of
its inhibition, and a brief summary of available DPP-4 inhibitors. Furthermore,
since protection against the overactivity of proteases is important for
restorating cardiac function and repair after myocardial damage, necrosis and
apoptosis, we propose that administration of a DPP-4 inhibitor may also be
beneficial following myocardial infarction by the prevention of cleavage of stem
cell chemoattractant cytokine SDF-1.
PMID- 27484975
TI - Study of Binding Interaction between Pif80 Protein Fragment and Aragonite.
AB - Pif is a crucial protein for the formation of the nacreous layer in Pinctada
fucata. Three non-acidic peptide fragments of the aragonite-binding domain
(Pif80) are selected, which contain multiple copies of the repeat sequence DDRK,
to study the interaction between non-acidic peptides and aragonite. The
polypeptides DDRKDDRKGGK (Pif80-11) and DDRKDDRKGGKDDRKDDRKGGK (Pif80-22) have
similar binding affinity to aragonite. Solid-state NMR data indicate that the
backbones of Pif80-11 and Pif80-22 peptides bound on aragonite adopt a random
coil conformation. Pif80-11 is a lot more effective than Pif80-22 in promoting
the nucleation of aragonite on the substrate of beta-chitin. Our results suggest
that the structural arrangement at a protein-mineral interface depends on the
surface structure of the mineral substrate and the protein sequence. The side
chains of the basic residues, which function as anchors to the aragonite surface,
have uniform structures. The role of basic residues as anchors in protein-mineral
interaction may play an important role in biomineralization.
PMID- 27484976
TI - Changes in Gastric Volume and Their Implications for Weight Loss after
Laparoscopic Sleeve Gastrectomy.
AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a relatively new surgical
technique for the treatment of morbid obesity. It is unclear whether the volume
of the gastric remnant can expand after surgery as a result of intraluminal
pressure maintained over time. If this were the case, the increased volume could
affect weight loss and the improvement in comorbidities. This study aims to
assess the evolution of residual gastric volume (RGV) during the first year after
LSG and its relationship with weight loss. MATERIAL AND METHODS: We conducted a
prospective study of 112 patients who underwent LSG from February 2009 to
December 2013. In order to measure the RGV after surgery, all patients were
evaluated radiologically by an esophagogastroduodenal (EGD) transit at 1 and 12
postoperative months. RESULTS: All patients showed a significant reduction in BMI
compared with the preoperative measurement (33.48 +/- 5.78 vs. 50.54 +/- 6.69
kg/m2; p < 0.001). Increased RGV was observed when comparing the results obtained
by EGD transit at 1 (68.39 +/- 25.89 cm3) and 12 postoperative months (122.58 +/-
38.76 cm3; p < 0.001). There was no association between increase in gastric
volume and weight loss at 1-year follow-up (r = 0.01; p = 0.910). CONCLUSIONS:
The volume of the gastric remnant increased significantly during the first year
after LSG. However, this increase was not associated with weight loss. Further
prospective research with longer follow-up periods is needed to confirm or
contrast the present results.
PMID- 27484977
TI - Arsenic, Lead, and Cadmium in U.S. Mushrooms and Substrate in Relation to Dietary
Exposure.
AB - Wild mushrooms can absorb high quantities of metal(loid)s, yet the concentration,
speciation, and localization of As, Pb, and Cd in cultivated mushrooms,
particularly in the United States, are unresolved. We collected 40 samples of 12
types of raw mushrooms from 2 geographic locations that produce the majority of
marketable U.S. mushrooms and analyzed the total As, Pb, and Cd content, the
speciation and localization of As in select samples, and assessed the metal
sources and substrate-to-fruit transfer at one representative farm. Cremini
mushrooms contained significantly higher total As concentrations than Shiitake
and localized the As differently; while As in Cremini was distributed throughout
the fruiting body, it was localized to the hymenophore region in Shiitake. Cd was
significantly higher in Royal Trumpet than in White Button, Cremini, and
Portobello, while no difference was observed in Pb levels among the mushrooms.
Concentrations of As, Pb, and Cd were less than 1 MUg g(-1) d.w. in all mushroom
samples, and the overall risk of As, Cd, and Pb intake from mushroom consumption
is low in the U.S. However, higher percentages of tolerable intake levels are
observed when calculating risk based on single serving-sizes or when substrate
contains elevated levels of metal(loid)s.
PMID- 27484979
TI - Solvent-dependent singlet oxygen lifetimes: temperature effects implicate
tunneling and charge-transfer interactions.
AB - The effect of solvent on the lifetime of singlet oxygen, O2(a(1)Deltag),
particularly the pronounced H/D solvent isotope effect, has drawn the attention
of chemists for almost 50 years. The currently accepted model for this phenomenon
is built on a foundation in which the electronic excitation energy of
O2(a(1)Deltag) is transferred to vibrational modes in a solvent molecule, with
oxygen returning to its ground electronic state, O2(X(3)Sigmag(-)). This model of
electronic-to-vibrational (e-to-v) energy transfer specifically focusses on the
solvent as a "sink" for the excitation energy of O2(a(1)Deltag). On the basis of
temperature-dependent changes in the solvent-mediated O2(a(1)Deltag) lifetime, we
demonstrate that this energy-sink-based model has limitations and needs to be re
formulated. We now show that the effect of solvent on the O2(a(1)Deltag) lifetime
is more reasonably interpreted by considering an activation barrier that reflects
the extent to which a solvent molecule perturbs the forbidden O2(a(1)Deltag) ->
O2(X(3)Sigmag(-)) transition. For a given solvent molecule, this barrier reflects
contributions from (a) the oxygen-solvent charge transfer state that mediates
nonradiative coupling between the O2(a(1)Deltag) and O2(X(3)Sigmag(-)) states,
and (b) vibrations of specific bonds in the solvent molecule. The latter
establishes connectivity to the desirable features of the energy-sink-based
model. Moreover, temperature-dependent H/D solvent isotope effects imply that
tunneling through this barrier plays a role in the mechanism for O2(a(1)Deltag)
deactivation, even at room temperature. Although we focus on a long-standing
problem involving O2(a(1)Deltag), our results and interpretation touch
fundamental issues of interest to chemists at large.
PMID- 27484978
TI - Monoamines and cortisol as potential mediators of the relationship between
exercise and depressive symptoms.
AB - A randomized controlled trial was conducted to assess the effects of exercise
plus pharmacotherapy on monoamine neurotransmitters (dopamine, noradrenaline,
adrenaline, serotonin) and cortisol levels. A total of 26 women with clinical
depression were randomly assigned to one of the two groups: aerobic exercise plus
pharmacotherapy or only pharmacotherapy. The exercise program consisted of
aerobic exercise, 45-50 min/session, three times/week, for 16 weeks. The
biological parameters were measured before and after the exercise program. Adding
exercise to pharmacotherapy had no additional effects on monoamines and cortisol
plasma levels. These data are preliminary outcomes from a small sample and should
be replicated.
PMID- 27484980
TI - Long-Term Outcomes and Prognostic Factors in Periampullary Carcinoma.
AB - PURPOSE: The aim of the study was to analyze the long-term survival and the
various prognostic factors that influence overall survival in patients undergoing
pancreaticoduodenectomy (PD) with non-pancreatic periampullary carcinomas.
METHODS: A retrospective analysis of consecutive patients diagnosed with non
pancreatic periampullary carcinomas who underwent PD at a tertiary cancer center
was performed. Univariate analysis of various prognostic factors influencing the
disease-free survival (DFS) was performed using log-rank test. Factors identified
to be significant in univariate analysis were included in the multivariate
analysis, which was performed using the Cox proportional hazard model. The
survival estimates were calculated by life-table method. Statistical significance
was considered when p value was <0.05. The SPSS v16.0.1 software was used for
statistical analysis. RESULTS: Between 1995 and 2010, 78 patients underwent PD
with or without (Whipple's operation) pylorus preservation for non-pancreatic
periampullary adenocarcinomas. Of these, eight patients received adjuvant
chemotherapy. The most common subsite was ampulla (60 patients), followed by the
second part duodenum (11 patients), and distal common bile duct (7 patients). The
median duration of follow-up of all patients in this study was 50 months. The
recurrence rate was 39.7 %. The 5-year disease-free survival and overall survival
was 57 %. Patients without nodal metastasis had a non-significant trend towards
better 5-year disease-free survival when compared to those with nodal metastasis
(64 vs 45 %, p = 0.11). On multivariate analysis, it was found that male gender
(p = 0.05) and presence of lymphovascular invasion (p = 0.04) predicted a
significantly poor 5-year disease-free survival. CONCLUSION: Periampullary
carcinomas have a favorable prognosis after surgery. Male gender and presence of
lymphovascular invasion are independent prognostic factors in patients diagnosed
with non-pancreatic periampullary carcinomas who underwent PD in this study.
PMID- 27484981
TI - Mechanisms behind Topoisomerase II SUMOylation in chromosome segregation.
PMID- 27484983
TI - Probing the Influence of Amino Acids on Photoluminescence from Carbon Nanotubes
Suspended with DNA.
AB - The quantitative analysis of amino acid levels in the human organism is required
for the early clinical diagnosis of a variety of diseases. In this work the
influence of 13 amino acid doping on the photoluminescence (PL) from the
semiconducting single-walled carbon nanotubes (SWNTs) suspended with single
stranded DNA (ssDNA) in water has been studied. Amino acid doping leads to the PL
enhancement and the strongest increase was found after cysteine doping of the
nanotube suspension while addition of other amino acids yielded the significantly
smaller effect. The emphasis of cysteine molecules is attributed to presence of
the reactive thiol group that turns cysteine into reducing agent that passivates
the p-defects on the nanotube sidewall and increases the PL intensity. The
reasons of PL enhancement after doping with other amino acids are discussed. The
response of nanotube PL to cysteine addition depends on the nanotube aqueous
suspension preparation with tip or bath sonication treatment. The enhancement of
the emission from different nanotube species after cysteine doping was analyzed
too. It was shown that the increase of the carbon nanotube PL at addition of
cysteine allows successful monitoring of the cysteine concentration in aqueous
solution in the range of 50-1000 MUM.
PMID- 27484982
TI - Meiotic pairing and gene expression disturbance in germ cells from an infertile
boar with a balanced reciprocal autosome-autosome translocation.
AB - Individuals carrying balanced constitutional reciprocal translocations generally
have a normal phenotype, but often present reproductive disorders. The aim of our
research was to analyze the meiotic process in an oligoasthenoteratospermic boar
carrying an asymmetric reciprocal translocation involving chromosomes 1 and 14.
Different multivalent structures (quadrivalent and trivalent plus univalent) were
identified during chromosome pairing analysis. Some of these multivalents were
characterized by the presence of unpaired autosomal segments with histone
gammaH2AX accumulation sometimes associated with the XY body. Gene expression in
spermatocytes was studied by RNA-DNA-FISH and microarray-based testis
transcriptome analysis. Our results revealed a decrease in gene expression for
chromosomes 1 and 14 and an up-regulated expression of X-chromosome genes for the
translocated boar compared with normal individuals. We hypothesized that the
observed meiotic arrest and reproductive failure in this boar might be due to
silencing of crucial autosomal genes (MSUC) and disturbance of meiotic sex
chromosome inactivation (MSCI). Further analysis revealed abnormal meiotic
recombination (frequency and distribution) and the production of a high rate of
unbalanced spermatozoa.
PMID- 27484984
TI - Synthesis, Aggregation Induced Emission and Mechanochromic Luminescence of New
beta-Diketone Derivatives Bearing Tetraphenylene Moieties.
AB - A series of beta-diketone derivatives bearing tetraphenylene (TPE) moieties were
synthesized and characterized. Their photophysical properties were investigated
systematically via spectroscopic and theoretical methods. All compounds exhibit
broad absorption bands between 300 and 450 nm, which are assigned to the 1pi-pi*
transition of the conjugated system mixed intramolecular charge-transfer (ICT)
transitions. Meanwhile, the emission of these compounds in solution at room
temperature (lambda em = 458 ~ 509 nm) can be attributed to the 1pi,pi*/1ICT
state. Introduction of freely rotatable TPE to conventional beta-diketone
luminophors quenches their light emissions in the solutions, but endows these
molecules with aggregation-induced emission (AIE) characteristics in the
condensed phase due to the restriction of intramolecular rotation. The
spectroscopic studies and theoretical calculations indicate that the
photophysical properties of these beta-diketone derivatives can be tuned by the
appended substituents, which would be useful for rational design of AIE compounds
with high solid state luminescence performance. Furthermore, these AIE-active
compounds exhibited distinct piezofluorochromic properties and switched
reversibly upon grinding-fuming. Their photophysical properties have been
investigated with the aim to provide a basis for elucidating the structure
property correlations and developing new multi-stimuli responsive luminescent
materials.
PMID- 27484985
TI - Relationship between fasting glucose levels and in-hospital mortality in Chinese
patients with acute myocardial infarction and diabetes mellitus: a retrospective
cohort study.
AB - BACKGROUND: Previous studies have demonstrated that elevated admission and
fasting glucose (FG) is associated with worse outcomes in patients with acute
myocardial infarction (AMI). However, the quantitative relationship between FG
levels and in-hospital mortality in patients with AMI remains unknown. The aim of
the study is to assess the prevalence of elevated FG levels in hospitalized
Chinese patients with AMI and diabetes mellitus and to determine the quantitative
relationship between FG levels and the in-hospital mortality as well as the
optimal level of FG in patients with AMI and diabetes mellitus. METHODS: A
retrospective study was carried out in 1856 consecutive patients admitted for AMI
and diabetes mellitus from 2002 to 2013. Clinical variables of baseline
characteristics, in-hospital management and in-hospital adverse outcomes were
recorded and compared among patients with different FG levels. RESULTS: Among all
patients recruited, 993 patients (53.5 %) were found to have FG >=100 mg/dL who
exhibited a higher in-hospital mortality than those with FG < 100 mg/dL (P <
0.001). Although there was a high correlation between FG levels and in-hospital
mortality in all patients (r = 0.830, P < 0.001), the relationship showed a J
curve configuration with an elevated mortality when FG was less than 80 mg/dL.
Using multivariate logistic regression models, we identified that age, FG levels
and Killip class of cardiac function were independent predictors of in-hospital
mortality in AMI patients with diabetes mellitus. CONCLUSIONS: More than half of
patients with AMI and diabetes mellitus have FG >=100 mg/dL and the relationship
between in-hospital mortality and FG level was a J-curve configuration. Both FG
>= 100 mg/dL and FG <80 mg/dL were identified to be independent predictors of in
hospital mortality and thus the optimal FG level in AMI patients with diabetes
mellitus appears to be 80-100 mg/dL.
PMID- 27484987
TI - Impact of e-cigarette refill liquid with or without nicotine on liver function in
adult rats.
AB - This study was conducted to evaluate the effects of e-cigarette refill liquid
administration alone or with nicotine on the antioxidant defense status,
functional and histopathological changes in adult rat liver tissue. For this
purpose, 32 rats were treated for 28 days as follows: control group was injected
intra-peritoneally with physiological saline; e-cigarette 0% treated group
received an intra-peritoneal injection of e-liquid without nicotine diluted in
physiological saline, e-cigarette-treated group received an intra-peritoneal
injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted
in physiological saline and nicotine-treated group received an intra-peritoneal
injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological
saline. In e-liquid without nicotine-exposed group, activities of the liver
biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline
phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress
indicators showed decreased total protein content, associated with a reduction in
the antioxidant enzymes activities superoxide dismutase, catalase and glutathione
S-transferase, and an elevation in malondialdehyde content, highlighting the
promotion of lipid peroxidation and oxidative stress. Histological studies
identified inflammatory cells infiltration and cell death. Thus, e-liquid seems
to promote oxidative tissue injuries, which in turn lead to the observed
histopathological finding. In comparison, nicotine alone induced less oxidative
stress and less histopathological disorders, whereas e-liquid with nicotine gave
rise to more histopathological injuries. Thereby, e-liquid, per se, is able to
induce hepatotoxicity and supplementation with nicotine worsens this state.
PMID- 27484986
TI - Therapeutic effects of paeonol on methyl-4-phenyl-1,2,3,6
tetrahydropyridine/probenecid-induced Parkinson's disease in mice.
AB - Paeonol is a major phenolic compound of the Chinese herb, Cortex Moutan, and is
known for its antioxidant, anti-inflammatory and antitumor properties. The
present study was designed to investigate the therapeutic potential and
underlying mechanisms of paeonol on a 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine/probenecid (MPTP/p)-induced mouse model of Parkinson's disease
(PD). MPTP (25 mg/kg), followed by probenecid (250 mg/kg), was administered via
i.p. injection for five consecutive days to induce the mouse model of PD. Paeonol
(20 mg/kg) was administrated orally for 21 days. Behavior was assessed using the
rotarod performance and open-field tests. Additionally, the levels of tyrosine
hydroxylase (TH), microglia, interleukin-1beta (IL-1beta), and brain-derived
neurotrophic factor (BDNF) in the substantia nigra pars compacta (SNpc) were
evaluated by immunohistochemical staining. MPTP/p-induced motor deficits were
observed to be significantly improved following long-term treatment with paeonol.
Paeonol treatment decreased MPTP/p-induced oxidative stress, as determined by
evaluating the activity levels of superoxide dismutase, catalase and glutathione.
Additionally, MPTP/p-induced neuroinflammation was assessed by examining the
levels of microglia and IL-1beta, which were significantly decreased following
paeonol treatment. Paeonol treatment improved the MPTP/p-induced dopaminergic
neurodegeneration, as measured by observing the increased TH level in the SNpc.
Furthermore, the BDNF level was significantly elevated in the paeonol treatment
group compared with mice treated with MPTP/p only. In conclusion, paeonol exerted
therapeutic effects in the MPTP/p-induced mouse model of PD, possibly by
decreasing the damage from oxidative stress and neuroinflammation, and by
enhancing the neurotrophic effect on dopaminergic neurons. The results
demonstrate paeonol as a potential novel treatment for PD.
PMID- 27484988
TI - Scar Assessment After Breast Augmentation Surgery with Axillary Incision versus
Inframammary Fold Incision: Long-Term Follow-Up in Chinese Patients.
AB - BACKGROUND: The inframammary fold (IMF) incision is widely used in Western
countries for breast augmentation surgery, whereas the axillary incision is the
dominant approach used in China, because many Chinese surgeons believe that the
Asian population has a higher risk of developing hypertrophic scars. However,
comparative data of scar assessment through different incisions in Chinese
patients are scarce. The aims of the study were as follows: (1) to evaluate the
outcomes of scar assessment using the Vancouver scar scale (VSS), combined with
patient satisfaction scoring, in the scar assessment after breast augmentation
surgery; (2) to compare the long-term cosmetic effects of surgical scars between
axillary and IMF incisions. METHODS: Consecutive patients coming to our
department for follow-up care at least 1 year after primary breast augmentation
surgeries with axillary and IMF incisions between January 1, 2014 and December
31, 2014 were included in the research. Internal consistency, inter-rater
reliability, and convergent validity were examined for the VSS and patient
satisfaction scoring. The baseline characteristics and scar scores were tested
using the Mann-Whitney U-test and Student's t test between the two groups.
RESULTS: Sixty-one patients underwent implantation surgeries through the axillary
incisions, and 17 patients through the IMF incisions. There were no significant
differences in age, follow-up time, body mass index, implant volume, or implant
projection between groups. Reliability and validity of the VSS and patient
satisfaction scoring were satisfactory. The scores of pigmentation were higher in
the IMF group than those in the axilla group with statistical significance (P <
0.05). The scores of other subscales, overall VSS scores, and patient
satisfaction were not statistically significant. The scars were significantly
longer in the axilla group compared with the IMF group (P < 0.05). CONCLUSIONS:
The VSS combined with patient satisfaction scoring constitutes an effective tool
to evaluate incision scars after augmentation mammaplasty. Scars in the axilla
and IMF can achieve comparable cosmetic effects and patient satisfaction in
Chinese women. Chinese patients with proper indications can receive breast
augmentation surgery through the IMF incision, with fewer risks and less trauma,
and get satisfactory scar appearance as through the axillary incision. LEVEL OF
EVIDENCE III: 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- 27484990
TI - Burkitt Lymphoma Presenting as an Intracardiac Mass: Case Report and Review of
Literature.
AB - BACKGROUND Non-neoplastic causes such as infections and thrombi account for most
intracardiac masses. Primary tumors such as myxomas and metastasis from breast
cancer, lung cancer, or melanomas account for many of the remaining cases.
Burkitt lymphoma manifesting as an intracardiac mass is a rare entity, with 21
cases reported in the English literature. CASE REPORT We report the case of a man
infected with human immunodeficiency virus (HIV) who presented with non-specific
cardiac symptoms and was later found to have intracardiac mass caused by Burkitt
lymphoma. His rapid decline with unexpected complications was reversed with
prompt management. Subsequent to induction, the patient achieved a near complete
response with considerable improvement in his condition. CONCLUSIONS Lymphoma
should be considered in the differential diagnosis of intracardiac masses.
Associated cardiac symptoms are frequently non-specific and can often be
overlooked or underappreciated. Burkitt lymphoma has a short doubling time and an
intracardiac lesion can become life-threatening in a matter of days. Early
recognition and prompt treatment are crucial to achieving optimal outcomes.
PMID- 27484989
TI - Lack of concordance between residual viremia and viral variants driving de novo
infection of CD4(+) T cells on ART.
AB - BACKGROUND: In most patients, current antiretroviral therapy (ART) regimens can
rapidly reduce plasma viral load. However, even after years of effective
treatment, a significant proportion of patients show residual plasma viremia
below the clinical detection limit. Although residual viremia might be associated
with increased chronic immune activation and morbidity, its origin and its
potential role in the replenishment of the viral reservoir during suppressive ART
is not completely understood. We performed an in-depth genetic analysis of the
total and episomal cell-associated viral DNA (vDNA) repertoire in purified CD4(+)
T cell subsets of three HIV-infected individuals, and used phylogenetic analysis
to explore its relationship with plasma viruses. RESULTS: The predominant
proviral reservoir was established in naive or memory (central and transitional)
CD4(+) T cell subsets in patients harboring X4- or R5-tropic viruses,
respectively. Regardless of the viral tropism, most plasma viruses detected under
suppressive ART resembled the proviral reservoir identified in effector and
transitional memory CD4(+) T-cell subsets in blood, suggesting that residual
viremia originates from these cells in either blood or lymphoid tissue. Most
importantly, sequences in episomal vDNA in CD4(+) T-cells were not well
represented in residual viremia. CONCLUSIONS: Viral tropism determines the
differential distribution of viral reservoir among CD4(+) T-cell subsets. In
spite of viral tropism, the effector and transitional memory CD4(+) T-cells
subsets are the main source of residual viremia during suppressive ART, even
though their contribution to the total proviral pool is small. However, the lack
of concordance between residual viremia and viral variants driving de novo
infection of CD4(+) T cells on ART may reflect the predominance of defective
plasma HIV RNA genomes. These findings highlight the need for monitoring the
multiple viral RNA/DNA persistence markers, based on their differential
contribution to viral persistence.
PMID- 27484991
TI - Preparation of chicken IgY against recombinant E2 protein of bovine viral
diarrhea virus (BVDV) and development of ELISA and ICA for BVDV detection.
AB - Bovine viral diarrhea virus (BVDV) infects cattle and may lead to persistent
infection (PI). The PI animals harbor BVDV throughout their life and become
immune tolerant against BVDV. Thus, diagnosis of this virus in herd is highly
important. Recombinant E2 protein expression (using pET-32a in Escherichia coli)
was confirmed by SDS-PAGE and Western blotting; then purified by Ni+ affinity
chromatography. Chickens were immunized with BVDV-E2 protein, and IgY antibodies
were extracted from egg yolk by PEG-6000. The peak titer of anti-BVDV-E2-IgY was
1:128,000 after the fifth immunization. IgY-based enzyme-linked immuno sorbent
assay (ELISA) and immunochromatographic assay (ICA) were further developed.
Coincidence of ELISA and ICA test with RT-PCR was 95.45 and 90.91%, respectively.
The anti-BVDV-E2 IgY could be used in routine screening of BVDV infection.
Besides, it can also be applicable while licensing and/or using live vaccines;
screening of imported products containing bovine serum and strong surveillance of
BVDV outbreaks.
PMID- 27484992
TI - Parallel or convergent evolution in human population genomic data revealed by
genotype networks.
AB - BACKGROUND: Genotype networks are representations of genetic variation data that
are complementary to phylogenetic trees. A genotype network is a graph whose
nodes are genotypes (DNA sequences) with the same broadly defined phenotype. Two
nodes are connected if they differ in some minimal way, e.g., in a single
nucleotide. RESULTS: We analyze human genome variation data from the 1,000
genomes project, and construct haploid genotype (haplotype) networks for 12,235
protein coding genes. The structure of these networks varies widely among genes,
indicating different patterns of variation despite a shared evolutionary history.
We focus on those genes whose genotype networks show many cycles, which can
indicate homoplasy, i.e., parallel or convergent evolution, on the sequence
level. CONCLUSION: For 42 genes, the observed number of cycles is so large that
it cannot be explained by either chance homoplasy or recombination. When
analyzing possible explanations, we discovered evidence for positive selection in
21 of these genes and, in addition, a potential role for constrained variation
and purifying selection. Balancing selection plays at most a small role. The 42
genes with excess cycles are enriched in functions related to immunity and
response to pathogens. Genotype networks are representations of genetic variation
data that can help understand unusual patterns of genomic variation.
PMID- 27484993
TI - Recapitulating epithelial tumor microenvironment in vitro using three dimensional
tri-culture of human epithelial, endothelial, and mesenchymal cells.
AB - BACKGROUND: Three-dimensional (3-D) cultures of cancer cells can potentially
bridge the gap between 2-D drug screening and in vivo xenografts. The objective
of this study was to characterize the cellular and extracellular matrix
characteristics of spheroids composed of human lung epithelial cells (epi),
pulmonary vascular endothelial (endo) cells, and human marrow-derived mesenchymal
stems cells (MSCs). METHODS: Spheroids composed of epi/endo/MSCs, termed herein
as synthetic tumor microenvironment mimics (STEMs), were prepared by the hanging
drop method. Cellular composition and distribution in the STEMs was characterized
using fluorescence microscopy. Induction of reactive oxygen species and
upregulation of efflux transporters was quantified using fluorometry and PCR,
respectively, and phenotypic markers were qualitatively assessed using
immunohistochemistry. RESULTS: STEMs exhibited three unique characteristics not
captured in other spheroid cultures namely, the presence of a spheroid core
devoid of epithelial cells and primarily composed of MSCs, a small viable
population of endothelial cells hypothesized to be closely associated with MSCs
within the hypoxic core, and discrete regions with high expression for vimentin
and cytokeratin-18, whose co-expression is co-related with enhanced metastasis.
Although cells within STEMs show elevated levels of reactive oxygen species and
mRNA for ABC-B1, an efflux transporter associated with drug resistance, they
exhibited only modest resistance to paclitaxel and gemcitabine in comparison to 2
D tri-cultures. CONCLUSIONS: The epi/endo/MSC spheroid model described herein
offers a promising platform for understanding tumor biology and drug testing in
vitro.
PMID- 27484994
TI - The influence of body composition on renal function in patients with coronary
artery disease and its prognostic significance: a retrospective cohort study.
AB - OBJECTIVE: We try to analyse the effect of renal functions on death in CAD
patients with different body compositions. METHODS: A retrospective analysis was
conducted in 2989 consecutive patients with CAD confirmed by coronary angiography
were enrolled and were grouped into two categories: basically preserved renal
function (PRF) (eGFR >=60 ml/min) and obviously reduced renal function (RRF)
(eGFR <60 ml/min). The influence of renal insufficiency on mortality of CAD was
detected in every tertile of body composition, including body mass index (BMI),
body fat (BF) and lean mass index (LMI). The end points were all-cause mortality.
RESULTS: The mean follow-up time was 29.1 +/- 12.5 months and death events
occurred in 271 cases. The percentage of patients with RRF was positively
correlated with BF and inversely correlated with the LMI, but no relationship to
BMI. The survival curves showed that the risk of death was significantly higher
in the RRF patients in all subgroups stratified using BMI, BF, or LMI (log rank
test, all p < 0.001). The COX multivariate regression analysis showed that the
risk of death was significantly higher in the RRF patients with high BF (HR 1.95,
CI 1.25-3.05) and low LMI (HR 1.82, CI 1.19-2.79). Meanwhile, risk of death was
significantly higher in RRF patients with a high BMI (HR 2.08, CI 1.22-3.55) or
low BMI (HR 1.98, CI 1.28-3.08) but this risk was not significant in patients
with a medium BMI (HR 1.12, 0.65-1.94). The subgroup analysis of patients with
acute coronary syndrome (ACS) showed similar results. CONCLUSIONS: For patients
with CAD, renal insufficiency was positively correlated with BF, inversely
correlated with LMI, and unrelated to BMI. The effect of renal insufficiency on
the risk of death of CAD was related to body composition.
PMID- 27484995
TI - Characteristics and trends in publication of scientific papers presented at the
European Congress of Radiology: a comparison between 2000 and 2010.
AB - OBJECTIVE: To determine journal publication rates of scientific papers presented
orally at the European Congress of Radiology (ECR) 2010, with comparison of
country data to ECR 2000. METHODS: All oral presentations from ECR 2010 were
evaluated for publication between 2010 and 2014 using the MEDLINE database.
Countries, collaborations, subspecialties, modalities and study design were
ranked by publication percentage. Chi-square tests were used to compare
publication percentages for each category of variables. Hazard ratios (HR) were
calculated for each country relative to the host nation, Austria. ECR 2010
country statistics were compared with analogous data from ECR 2000. RESULTS: In
total, 360/840 abstracts were subsequently published (43 %). The author's country
of origin (p = 0.02), subspecialty (p = 0.02) and study design (p = 0.001) were
significantly associated with subsequent publication. Switzerland, the
Netherlands, France and Germany were among the top six countries by publication
percentage in 2000 and 2010. In 2010, Switzerland had the highest publication
rate (62 %) and HR in comparison to Austria (HR 2.62 [1.31-5.25], p = 0.01).
Three Asian nations increased relative publication rates over the 10-year period.
CONCLUSION: Several European nations consistently convert relatively high
percentages of oral abstracts at ECR into publications, and the influence of
Asian countries is increasing. MAIN MESSAGES: * Certain European nations
consistently publish high percentages of orally presented abstracts at ECR. * The
influence of several Asian countries on ECR is increasing. * Country,
subspecialty and study design are significantly associated with journal
publication. * Authors collaborating internationally have the highest publication
rates and mean impact factors. * Among all modalities, PET-CT, MRI and CT have
the highest publication percentages.
PMID- 27484997
TI - Effects of unequal electrode pairs on an x-strip thickness-shear mode multi
channel quartz crystal microbalance.
AB - We study the thickness-shear vibrations of an x-strip monolithic piezoelectric
plate made from AT-cut quartz crystals with two unequal electrode pairs. The
Tiersten-Smythe scalar differential equations for electroded and unelectroded
quartz plates are separately employed, resulting in free vibration distributions
and frequencies of operating modes. The vibrations of these operating modes are
mainly trapped in the electroded regions. The loss of the structural symmetry can
lead to a weak vibration interaction between two electroded regions. The
influences of electrode difference on the vibration and frequency interference
between two adjacent resonators are investigated in detail. The obtained results
provide a fundamental reference to the design and optimization of multi-channel
quartz crystal microbalance.
PMID- 27484996
TI - Checklist to operationalize measurement characteristics of patient-reported
outcome measures.
AB - BACKGROUND: The purpose of this study was to advance a checklist of evaluative
criteria designed to assess patient-reported outcome (PRO) measures'
developmental measurement properties and applicability, which can be used by
systematic reviewers, researchers, and clinicians with a varied range of
expertise in psychometric measure development methodology. METHODS: A directed
literature search was performed to identify original studies, textbooks,
consensus guidelines, and published reports that propose criteria for assessing
the quality of PRO measures. Recommendations from these sources were iteratively
distilled into a checklist of key attributes. Preliminary items underwent
evaluation through 24 cognitive interviews with clinicians and quantitative
researchers. Six measurement theory methodological novices independently applied
the final checklist to assess six PRO measures encompassing a variety of methods,
applications, and clinical constructs. Agreement between novice and expert scores
was assessed. RESULTS: The distillation process yielded an 18-item checklist with
six domains: (1) conceptual model, (2) content validity, (3) reliability, (4)
construct validity, (5) scoring and interpretation, and (6) respondent burden and
presentation. With minimal instruction, good agreement in checklist item ratings
was achieved between quantitative researchers with expertise in measurement
theory and less experienced clinicians (mean kappa 0.70; range 0.66-0.87).
CONCLUSIONS: We present a simplified checklist that can help guide systematic
reviewers, researchers, and clinicians with varied measurement theory expertise
to evaluate the strengths and weakness of candidate PRO measures' developmental
properties and the appropriateness for specific applications.
PMID- 27485001
TI - Checkpoint Immunotherapy: Picking a Winner.
AB - Robust biomarkers of response that predict which patients will or will not
respond to immune checkpoint blockade need to be identified. New data suggest
that the presence of an adaptive immune signature in the tumor biopsies of
patients with melanoma early on therapy compared to pretreatment can identify
responders from nonresponders. Cancer Discov; 6(8); 818-20. (c)2016 AACR.See
related article by Chen et al., p. 827.
PMID- 27485002
TI - Adipocytes and Neutrophils Give a Helping Hand to Pancreatic Cancers.
AB - Obesity-induced inflammation can build up a confined microenvironment in
pancreatic adenocarcinoma that is associated with increased desmoplasia,
neutrophil recruitment, reduced delivery of chemotherapeutic drugs, and immune
evasion. Targeting molecular pathways empowering this circuit might represent a
necessary measure to reach clinical efficacy for combination therapies in
patients with excess body weight. Cancer Discov; 6(8); 821-3. (c)2016 AACR.See
related article by Incio et al., p. 852.
PMID- 27484998
TI - A Korean multi-center, real-world, retrospective study of first-line pazopanib in
unselected patients with metastatic renal clear-cell carcinoma.
AB - BACKGROUND: The efficacy and/or tolerability of pazopanib in patients with
metastatic renal cell carcinoma (mRCC) have been found to differ in Western and
Asian populations. This retrospective multicenter study analyzed the results of
first-line pazopanib treatment in 93 consecutive patients with mRCC who were
treated at the medical oncology departments of three tertiary cancer centers in
Seoul, Korea. METHODS: The decision to administer pazopanib as first-line therapy
was at the discretion of the treating physician in all patients with mRCC.
Patients enrolled in clinical trials were excluded to ensure that the results
would reflect real-world outcomes representative of daily clinical settings. All
patients received 800 mg/day pazopanib. Outcomes included response rate,
progression-free survival (PFS), overall survival (OS), and safety. RESULTS: The
93 patients included72 (77 %) male and 21 (23 %) female individuals, of median
age 65 years (range, 19-84 years). The median number of metastatic sites per
patient was two (range, 1-5), with the lungs being the most frequently involved
site. Most patients had favorable (n = 46) or intermediate (n = 36) risk as
determined by Memorial Sloan Kettering Cancer Center criteria. Pazopanib was
generally welltolerated: the major hematologic adverse effect was grade 1/2
anemia (14 %); and the most frequently observed non-hematologic toxicity was
grade 1/2 mucositis (22 %), followed by hair discoloration and hypertension. Of
the 93 patients, three (3 %) showed complete response, 52 (56 %) showed partial
response, and 21 (23 %) showed stable disease, making the objective response rate
59 % and the disease control rate 82 %. At a median follow-up of 21 months, the
estimated median PFS and OS were 12.2 months (95 % confidence interval, 7.1-17.4
months) and 21.9 months (95 % confidence interval, 12.9-30.9 months),
respectively. CONCLUSIONS: In this retrospective study, first-line therapy with
pazopanib demonstrated clinically relevant efficacy and tolerability in
unselected real-world Korean patients with mRCC. OS and PFS of these Korean
patients were similar to those reported in phase III trials.
PMID- 27485003
TI - Genomic Amplifications Cause False Positives in CRISPR Screens.
AB - In CRISPR-based screens for essential genes, Munoz and colleagues and Aguirre and
colleagues show that gene-independent targeting of genomic amplifications in
human cancer cell lines reduces proliferation or survival. The correlation
between CRISPR target site copy number and lethality demonstrates the need for
scrutiny and complementary approaches to rule out off-target effects and false
positives in CRISPR screens. Cancer Discov; 6(8); 824-6. (c)2016 AACR.See related
article by Munoz et al., p. 900See related article by Aguirre et al., p. 914.
PMID- 27485004
TI - Cerebral vasoconstriction reactions and plasma levels of ETBR, ET-1, and eNOS in
patients with chronic high altitude disease.
AB - The aim of the present study was to examine cerebral vasoconstriction in patients
with chronic high altitude disease [cerebrovascular reactivity (CVR)], and to
evaluate differences in alterations of brain vascular contractile reactivity of
chronic mountain sickness (CMS) patients and healthy controls. Alterations of
endothelin (ET) and its receptor, as well as endothelial nitric oxide synthase
(eNOS) levels in the plasma were examined to determine the cerebral reservation
capacities in CMS patients. Transcranial Doppler ultrasound and carbon dioxide
analysis methods were used to detect the CVR variances. At the same time, enzyme
linked immunosorbent assay approaches were utilized to detect the ET and ET B
receptor and the eNOS levels in serum of the CMS patients and healthy controls.
CVR and CVRI levels in CMS patients were lower than those of the healthy control
subjects and the difference was statistically significant (P<0.05). By contrast,
eNOS and ET-1 levels were not statistically significant for CMS and healthy
controls (P>0.05). However, the ET receptor concentration level was higher in CMS
than the healthy controls. Thus, ET-1 may not be a direct etiological variation
but may play compensatory roles in CMS patients. The results of the study may
provide scientific clues for the prevention and treatment of CMS with higher
blood coagulation states of cerebral infarction in patients with chronic high
altitude disease.
PMID- 27485006
TI - Treatment for non-thyroidal illness syndrome in advanced chronic kidney disease:
a single-blind controlled study.
AB - AIM: Non-thyroidal illness syndrome (NTIS) is common among patients with advanced
chronic kidney disease (CKD) and is strongly associated with poor prognosis.
However, it remains unclear in how to correct this disorder and this study aimed
to evaluate the effectiveness of sodium bicarbonate (SB) and N-acetyl-cysteine
(NAC) for correcting NTIS status. METHODS: Patients with CKD stage 3-4 were
single-blind, placebo-controlled treated with placebo, SB, or NAC for 18 weeks.
The primary end points were the correction of NTIS and the occurrence of end
stage renal disease (ESRD). The secondary point was the change in estimated
glomerular filtration rate (eGFR) after the follow-up. RESULTS: The Kaplan-Meier
survival analysis showed significant lower correcting ratio of NTIS in control
group compared with SB group [Hazard ratio (HR) 0.19, 95 % confidence interval
(CI) 0.04-0.89, p = 0.035] and NAC group (HR 0.09, 95 % CI 0.02-0.38, p = 0.001),
and increased ESRD risk in control group than in SB group (HR 1.97, 95 % CI 1.02
3.84, p = 0.045) and NAC group (HR 5.50, 95 % CI 2.23-13.57, p < 0.001). The Cox
regression analysis demonstrated significantly different effectiveness of
placebo, SB and NAC on NTIS correction and ESRD risk, p < 0.05, respectively.
Variance analysis displayed a greater reduction in eGFR in controls than in SB (p
= 0.044) and NAC group (p < 0.001). CONCLUSION: SB and NAC are effective in
promoting the recovery from NTIS status and delaying the deterioration of renal
function in advanced CKD patients.
PMID- 27485005
TI - A proteomics approach reveals molecular manipulators of distinct cellular
processes in the salivary glands of Glossina m. morsitans in response to
Trypanosoma b. brucei infections.
AB - BACKGROUND: Glossina m. morsitans is the primary vector of the Trypanosoma brucei
group, one of the causative agents of African trypanosomoses. The parasites
undergo metacyclogenesis, i.e. transformation into the mammalian-infective
metacyclic trypomastigote (MT) parasites, in the salivary glands (SGs) of the
tsetse vector. Since the MT-parasites are largely uncultivable in vitro,
information on the molecular processes that facilitate metacyclogenesis is
scanty. METHODS: To bridge this knowledge gap, we employed tandem mass
spectrometry to investigate protein expression modulations in parasitized (T. b.
brucei-infected) and unparasitized SGs of G. m. morsitans. We annotated the
identified proteins into gene ontologies and mapped the up- and downregulated
proteins within protein-protein interaction (PPI) networks. RESULTS: We
identified 361 host proteins, of which 76.6 % (n = 276) and 22.3 % (n = 81) were
up- and downregulated, respectively, in parasitized SGs compared to unparasitized
SGs. Whilst 32 proteins were significantly upregulated (> 10-fold), only salivary
secreted adenosine was significantly downregulated. Amongst the significantly
upregulated proteins, there were proteins associated with blood feeding,
immunity, cellular proliferation, homeostasis, cytoskeletal traffic and
regulation of protein turnover. The significantly upregulated proteins formed
major hubs in the PPI network including key regulators of the Ras/MAPK and
Ca(2+)/cAMP signaling pathways, ubiquitin-proteasome system and mitochondrial
respiratory chain. Moreover, we identified 158 trypanosome-specific proteins,
notable of which were proteins in the families of the GPI-anchored surface
glycoproteins, kinetoplastid calpains, peroxiredoxins, retrotransposon host spot
multigene and molecular chaperones. Whilst immune-related trypanosome proteins
were over-represented, membrane transporters and proteins involved in translation
repression (e.g. ribosomal proteins) were under-represented, potentially
reminiscent of the growth-arrested MT-parasites. CONCLUSIONS: Our data implicate
the significantly upregulated proteins as manipulators of diverse cellular
processes in response to T. b. brucei infection, potentially to prepare the MT
parasites for invasion and evasion of the mammalian host immune defences. We
discuss potential strategies to exploit our findings in enhancement of
trypanosome refractoriness or reduce the vector competence of the tsetse vector.
PMID- 27485007
TI - Comparative effectiveness of angiotensin receptor blockers vs. angiotensin
converting enzyme inhibitors on cardiovascular outcomes in patients initiating
peritoneal dialysis.
AB - BACKGROUND: There is evidence that angiotensin-converting enzyme inhibitors
(ACEI) and angiotensin-II receptor blockers (ARB) may reduce cardiovascular (CV)
risk in patients undergoing peritoneal dialysis (PD), but no studies have
compared the effectiveness between these drug classes. In this observational
cohort study, we compared the association of ARB vs. ACEI use on CV outcomes in
patients initiating PD. METHODS: We identified from the US Renal Data System all
adult patients who initiated PD from 2007 to 2011 and participated in Medicare
Part D, a federal prescription drug benefits program, for the first 90 days of
dialysis. Patients who filled a prescription for an ACEI or ARB in those 90 days
were considered users. We excluded patients who used both ACEI and ARB. We
applied Cox proportional hazards regression to an inverse probability of
treatment-weighted cohort to estimate the hazard ratios (HR) for the combined
outcome of all-cause death, ischemic stroke, or myocardial infarction; all-cause
mortality; and CV death. RESULTS: Among 1892 patients using either drug class, 39
% were ARB users. We observed 624 events over 2,898 person-years of follow-up,
for a composite event rate of 22 events per 100 person-years. We observed no
differences between ARB vs. ACEI users: composite outcome HR 0.94, 95 %
confidence interval (CI) 0.79-1.11; all-cause mortality HR 0.92, 95 % CI 0.76
1.10; CV death HR: 1.06, 95 % CI 0.80-1.41. CONCLUSION: We identified no
significant difference in the risks of CV events or death between users of ARBs
vs. ACEIs in patients initiating PD, thus supporting their mostly interchangeable
use in this population.
PMID- 27485008
TI - Substrate Factors Determine Roadside Vegetation Structure and Species Richness: A
Case Study Along a Meridional Gradient in Fennoscandia.
AB - This study assessed the effects of road-related alteration of substrate,
including increased salinity, on vegetation along a meridional gradient in
Fennoscandia. Vegetation community composition were surveyed in 29 randomly
selected 1-m(2) sized roadside plots. Number of plant species and plant cover (%)
on the plots were positively interrelated (p < 0.0001). Both variables also
decreased towards the north and with increasing coarseness of the substrate.
Canonical correspondence analysis (CCA) indicated that roadside vegetation
diversity and composition were most related to the importance of the road (i.e.
its size and traffic intensity) and substrate pH. Road importance affects plant
dispersal, whereas substrate pH was found to be a factor limiting growth. CCA
indicated also that vegetation composition was affected by the meridional
gradient and by the substrate salinity; both substrate salinity pH and salinity
were not related to meridional gradient. Our results indicate that roadside
vegetation diversity and composition is driven by natural and anthropogenic
factors.
PMID- 27485009
TI - Continued Studies on the Effects of Simazine on the Liver Histological Structure
and Metamorphosis in the Developing Xenopus laevis.
AB - This study continued our previous work (Sai et al. in Bull Environ Contam Toxicol
95:157-163, 2015a) by analysing the effects of simazine on the liver histological
structure and metamorphosis in the developing Xenopus laevis. Tadpoles (Nieuwkoop
Faber stage 46) were exposed to simazine at 0.1, 1.2, 11.0 and 100.9 MUg/L for
100 days. When tadpoles were exposed to simazine at 11.0 and 100.9 ug/L, an
increased mortality and damaged liver tissues were observed together with
significant inhibition of percent of X. laevis completing metamorphosis on days
80 and 90 and prolonged time of completing metamorphosis. On the other hand, we
found that simazine has no significant effects on liver weight and altered
hepatosomatic index. Results of this study may be considered to inform risk
assessment of the effects of simazine on the development of X. laevis.
PMID- 27485010
TI - Prevalence and correlates of achieving recommended physical activity levels among
children living in rural South Asia-A multi-centre study.
AB - BACKGROUND: We report the prevalence of recommended physical activity levels
(RPALs) and examine the correlates of achieving RPALs in rural South Asian
children and analyse its association with anthropometric outcomes. METHODS: This
analysis on rural South Asian children aged 5-14 years (n = 564) is a part of the
Chronic Disease Risk Factor study conducted at three sites in India (Chennai n =
146; Goa n = 218) and Bangladesh (Matlab; n = 200). Data on socio-demographic and
lifestyle factors (physical activity (PA); diet) were collected using an
interviewer-administered questionnaires, along with objective anthropometric
measurements. Multivariate logistic regression models were used to examine
whether RPALs (active travel to school (yes/no); leisure-time PA >= 1 h/day;
sedentary-activity <= 2 h/day) were associated with socio-demographic factors,
diet and other forms of PA. Multivariate linear regression models were used to
investigate associations between RPALs and anthropometrics (BMI- and waist z
scores). RESULTS: The majority of children (71.8 %) belonged to households where
a parent had at least a secondary education. Two-thirds (66.7 %) actively
travelled to school; 74.6 % reported >=1 h/day of leisure-time PA and 55.7 % had
<=2 h/day of sedentary-activity; 25.2 % of children reported RPALs in all three
dimensions. Older (10-14 years, OR = 2.0; 95 % CI: 1.3, 3.0) and female (OR =
1.7; 95 % CI: 1.1, 2.5) children were more likely to travel actively to school.
Leisure-time PA >= 1 h/day was more common among boys (OR = 2.5; 95 % CI: 1.5,
4.0), children in Matlab, Bangladesh (OR = 3.0; 95 % CI: 1.6, 5.5), and those
with higher processed-food consumption (OR = 2.3; 95 % CI: 1.2, 4.1). Sedentary
activity <= 2 h/day was associated with younger children (5-9 years, OR = 1.6; 95
% CI: 1.1, 2.4), children of Goa (OR = 3.5; 95 % CI: 2.1, 6.1) and Chennai (OR =
2.5; 95 % CI: 1.5, 4.3) and low household education (OR = 2.1; 95 % CI: 1.1,
4.1). In multivariate analyses, sedentary activity <= 2 h/day was associated with
lower BMI-z-scores (beta = -0.3; 95 % CI: -0.5, -0.08) and lower waist-z-scores
(beta = -1.1; 95 % CI: -2.2, -0.07). CONCLUSION: Only one quarter of children in
these rural areas achieved RPAL in active travel, leisure and sedentary activity.
Improved understanding of RPAL in rural South Asian children is important due to
rapid socio-economic transition.
PMID- 27485011
TI - Tolerogenic dendritic cells for reprogramming of lymphocyte responses in
autoimmune diseases.
AB - Dendritic cells (DCs) control immune responses by driving potent inflammatory
actions against external and internal threats while generating tolerance to self
and harmless components. This duality and their potential to reprogram immune
responses in an antigen-specific fashion have made them an interesting target for
immunotherapeutic strategies to control autoimmune diseases. Several protocols
have been described for in vitro generation of tolerogenic DCs (tolDCs) capable
of modulating adaptive immune responses and restoring tolerance through different
mechanisms that involve anergy, generation of regulatory lymphocyte populations,
or deletion of potentially harmful inflammatory T cell subsets. Recently, the
capacity of tolDCs to induce interleukin (IL-10)-secreting regulatory B cells has
been demonstrated. In vitro assays and rodent models of autoimmune diseases
provide insights to the molecular regulators and pathways enabling tolDCs to
control immune responses. Here we review mechanisms through which tolDCs modulate
adaptive immune responses, particularly focusing on their suitability for
reprogramming autoreactive CD4+ effector T cells. Furthermore, we discuss recent
findings establishing that tolDCs also modulate B cell populations and discuss
clinical trials applying tolDCs to patients with autoimmune diseases.
PMID- 27485012
TI - Complement and thrombosis in the antiphospholipid syndrome.
AB - The involvement of complement activation in the pathophysiology of
antiphospholipid syndrome (APS) was first reported in murine models of
antiphospholipid antibody (aPL)-related pregnancy morbidities. We previously
reported that complement activation is prevalent and may function as a source of
procoagulant cell activation in the sera of APS patients. Recently,
autoantibodies against C1q, a component of complement 1, were reported to be
correlated with complement activation in systemic lupus erythematosus. These
antibodies target neoepitopes of deformed C1q bound to various molecules (i.e.,
anionic phospholipids) and induce accelerated complement activation. We found
that anti-C1q antibodies are more frequently detected in primary APS patients
than in control patients and in refractory APS patients with repeated thrombotic
events. The titer of anti-C1q antibodies was significantly higher in refractory
APS patients than in APS patients without flare. The binding of C1q to anionic
phospholipids may be associated with the surge in complement activation in
patients with anti-C1q antibodies when triggered by 'second-hit' biological
stressors such as infection. Such stressors will induce overexpression of anionic
phospholipids, with subsequent increases in deformed C1q that is targeted by anti
C1q antibodies.
PMID- 27485013
TI - From VGKC to LGI1 and Caspr2 encephalitis: The evolution of a disease entity over
time.
AB - A wide variety of clinical syndromes has been associated with antibodies to
voltage-gated potassium channels (VGKCs). Six years ago, it was discovered that
patients do not truly have antibodies to potassium channels, but to associated
proteins. This enabled the distinction of three VGKC-positive subgroups: anti
LGI1 patients, anti-Caspr2 patients and VGKC-positive patients lacking both
antibodies. Patients with LGI1-antibodies have a limbic encephalitis, often with
hyponatremia, and about half of the patients have typical faciobrachial dystonic
seizures. Caspr2-antibodies cause a more variable syndrome of peripheral or
central nervous system symptoms, almost exclusively affecting older males.
Immunotherapy seems to be beneficial in patients with antibodies to LGI1 or
Caspr2, stressing the need for early diagnosis. Half of the VGKC-positive
patients lack antibodies to both LGI1 and Caspr2. This is a heterogeneous group
of patients with a wide variety of clinical syndromes, raising the question
whether VGKC-positivity is truly a marker of disease in these patients. Data
regarding this issue are limited, but a recent study did not show any clinical
relevance of VGKC-positivity in the absence of antibodies to LGI1 and Caspr2. The
three VGKC-positive subgroups are essentially different, therefore, the lumping
term 'VGKC-complex antibodies' should be abolished.
PMID- 27485014
TI - Science Signaling Podcast for 2 August 2016: Patient-specific protein complexes.
AB - This Podcast features an interview with Adam Schrum and Steven Neier, authors of
a Research Article that appears in the 2 August 2016 issue of Science Signaling,
about a method for identifying protein-protein interactions in patient tissue
samples. The authors used this method to compare signaling complexes downstream
of the T cell receptor in T cells from healthy skin with those in T cells from
the skin of patients with the autoimmune disease alopecia areata. The study
revealed differences in the relative abundance of some protein complexes between
T cells from the control and patient groups. This technique could be adapted for
use as a diagnostic tool to stratify patients by molecular phenotype and predict
the therapeutic strategy that is likely to work best for each patient.Listen to
Podcast.
PMID- 27485016
TI - Small heterodimer partner SHP mediates liver X receptor (LXR)-dependent
suppression of inflammatory signaling by promoting LXR SUMOylation specifically
in astrocytes.
AB - Liver X receptors (LXRs) suppress the expression of inflammatory genes in a
context-specific manner. In astrocytes, SUMOylation of LXRs promotes their anti
inflammatory effects. We found that small heterodimer partner (SHP), also known
as NR0B2 (nuclear receptor subfamily 0, group B, member 2), facilitates the anti
inflammatory actions of LXRs by promoting their SUMOylation. Knockdown of SHP
abrogated SUMOylation of LXRs, preventing their anti-inflammatory effects, in
primary rat astrocytes but not macrophages. The underlying mechanisms differed
according to LXR isoform. SHP promoted SUMO2 and SUMO3 attachment to LXRalpha by
interacting directly with the histone deacetylase and E3 SUMO ligase HDAC4. In
contrast, SHP promoted SUMO1 attachment to LXRbeta by stabilizing the E3 SUMO
ligase PIAS1. SHP bound PIAS1 and disrupted its interaction with the E3 ubiquitin
ligase SIAH1. Knocking down SIAH1 rescued LXRbeta SUMOylation in SHP-deficient
astrocytes. Our data collectively suggested that SHP mediates the anti
inflammatory actions of LXRs through differential regulation of receptor
SUMOylation specifically in astrocytes, thereby revealing potential avenues for
therapeutic development in diseases associated with brain inflammation.
PMID- 27485015
TI - Peripheral motor neuropathy is associated with defective kinase regulation of the
KCC3 cotransporter.
AB - Using exome sequencing, we identified a de novo mutation (c.2971A>G; T991A) in
SLC12A6, the gene encoding the K(+)-Cl(-) cotransporter KCC3, in a patient with
an early-onset, progressive, and severe peripheral neuropathy primarily affecting
motor neurons. Normally, the WNK kinase-dependent phosphorylation of T(991)
tonically inhibits KCC3; however, cell swelling triggers Thr(991)
dephosphorylation to activate the transporter and restore cell volume. KCC3 T991A
mutation in patient cells abolished Thr(991) phosphorylation, resulted in
constitutive KCC3 activity, and compromised cell volume homeostasis.
KCC3(T991A/T991A) mutant mice exhibited constitutive KCC3 activity and
recapitulated aspects of the clinical, electrophysiological, and
histopathological findings of the patient. These results suggest that the
function of the peripheral nervous system depends on finely tuned, kinase
regulated KCC3 activity and implicate abnormal cell volume homeostasis as a
previously unreported mechanism of axonal degeneration.
PMID- 27485017
TI - Multiplex matrix network analysis of protein complexes in the human TCR
signalosome.
AB - Multiprotein complexes transduce cellular signals through extensive interaction
networks, but the ability to analyze these networks in cells from small clinical
biopsies is limited. To address this, we applied an adaptable multiplex matrix
system to physiologically relevant signaling protein complexes isolated from a
cell line or from human patient samples. Focusing on the proximal T cell receptor
(TCR) signalosome, we assessed 210 pairs of PiSCES (proteins in shared complexes
detected by exposed surface epitopes). Upon stimulation of Jurkat cells with
superantigen-loaded antigen-presenting cells, this system produced high
dimensional data that enabled visualization of network activity. A comprehensive
analysis platform generated PiSCES biosignatures by applying unsupervised
hierarchical clustering, principal component analysis, an adaptive nonparametric
with empirical cutoff analysis, and weighted correlation network analysis. We
generated PiSCES biosignatures from 4-mm skin punch biopsies from control
patients or patients with the autoimmune skin disease alopecia areata. This
analysis distinguished disease patients from the controls, detected enhanced
basal TCR signaling in the autoimmune patients, and identified a potential
signaling network signature that may be indicative of disease. Thus, generation
of PiSCES biosignatures represents an approach that can provide information about
the activity of protein signaling networks in samples including low-abundance
primary cells from clinical biopsies.
PMID- 27485018
TI - Development of an open-source web-based intervention for Brazilian smokers - Viva
sem Tabaco.
AB - BACKGROUND: Web-based interventions for smoking cessation available in Portuguese
do not adhere to evidence-based treatment guidelines. Besides, all existing web
based interventions are built on proprietary platforms that developing countries
often cannot afford. We aimed to describe the development of "Viva sem Tabaco",
an open-source web-based intervention. RESULTS: The development of the
intervention included the selection of content from evidence-based guidelines for
smoking cessation, the design of the first layout, conduction of 2 focus groups
to identify potential features, refinement of the layout based on focus groups
and correction of content based on feedback provided by specialists on smoking
cessation. At the end, we released the source-code and intervention on the
Internet and translated it into Spanish and English. CONCLUSIONS: The
intervention developed fills gaps in the information available in Portuguese and
the lack of open-source interventions for smoking cessation. The open-source
licensing format and its translation system may help researchers from different
countries deploying evidence-based interventions for smoking cessation.
PMID- 27485020
TI - Biological maturity-associated variance in peak power output and momentum in
academy rugby union players.
AB - The study aimed to evaluate the mediating effect of biological maturation on
anthropometrical measurements, performance indicators and subsequent selection in
a group of academy rugby union players. Fifty-one male players 14-17 years of age
were assessed for height, weight and BMI, and percentage of predicted mature
status attained at the time of observation was used as an indicator of maturity
status. Following this, initial sprint velocity (ISV), Wattbike peak power output
(PPO) and initial sprint momentum (ISM) were assessed. A bias towards on-time (n
= 44) and early (n = 7) maturers was evident in the total sample and magnified
with age cohort. Relative to UK reference values, weight and height were above
the 90th and 75th centiles, respectively. Significant (p <= .01) correlations
were observed between maturity status and BMI (r = .48), weight (r = .63) and
height (r = .48). Regression analysis (controlling for age) revealed that
maturity status and height explained 68% of ISM variance; however, including BMI
in the model attenuated the influence of maturity status below statistical
significance (p = .72). Height and BMI explained 51% of PPO variance, while no
initial significant predictors were identified for ISV. The sample consisted of
players who were on-time and early in maturation with no late maturers
represented. This was attributable, in part, to the mediating effect of
maturation on body size, which, in turn, predicted performance variables.
PMID- 27485019
TI - Resurgence of Schmallenberg Virus in Belgium after 3 Years of Epidemiological
Silence.
AB - In spring 2016, three years after the last reported outbreak of Schmallenberg
virus (SBV) in Belgium, an abortion was notified in a two year old Holstein
heifer that previously had not been vaccinated against SBV. The autopsy of the
eight-month-old malformed foetus revealed hydrocephalus, torticollis and
arthrogryposis. Foetal brain tissue and blood were found to be SBV-positive by RT
PCR and ELISA tests, respectively. Evidencing the circulation of SBV in Belgium
in the autumn 2015 is important to anticipate future outbreaks and advise
veterinarians about the risks associated with calving, as more bovine foetuses
might have been infected.
PMID- 27485021
TI - Complex band structure of topological insulator Bi2Se3.
AB - Topological insulators are very interesting from a fundamental point of view, and
their unique properties may be useful for electronic and spintronic device
applications. From the point of view of applications it is important to
understand the decay behavior of carriers injected in the band gap of the
topological insulator, which is determined by its complex band structure (CBS).
Using first-principles calculations, we investigate the dispersion and symmetry
of the complex bands of Bi2Se3 family of three-dimensional topological
insulators. We compare the CBS of a band insulator and a topological insulator
and follow the CBS evolution in both when the spin-orbit interaction is turned
on. We find significant differences in the CBS linked to the topological band
structure. In particular, our results demonstrate that the evanescent states in
Bi2Se3 are non-trivially complex, i.e. contain both the real and imaginary
contributions. This explains quantitatively the oscillatory behavior of the band
gap obtained from Bi2Se3 (0 0 0 1) slab calculations.
PMID- 27485022
TI - Hamostaseologie - Progress in Haemostasis. Recent achievements and future
directions.
PMID- 27485023
TI - Molecular complexity of the megakaryocyte-platelet system in health and disease.
PMID- 27485024
TI - Cellular and molecular mechanisms of acute exposure to sulfur mustard: a
systematic review.
AB - CONTEXT: Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent
in several battles and is still a potential worldwide menace. Besides local
absorption, particularly in the skin, eyes and lungs, systemic spread of the
agent also has detrimental effects on gonads, bone marrow and nervous system.
Moreover, chronic exposure of SM to respiratory system causes death. Inducing
oxidative stress, and disturbing DNA and tissue repair systems, inflammation and
cell death signaling pathways have been introduced as molecular mechanisms of the
injury. METHODS: In this systematic review, more than 1200 (2000-2014) articles
focusing on gross or molecular pathological reports in the acute phase of the
respiratory injury after SM exposure were reviewed, followed by two different
layers of gross and molecular pathological data (clinic and laboratory)
integrated together in a spatio-temporal order. Role of epithelial, neutrophil
and macrophage cells and three signaling pathways of inflammation, oxidative
stress and cell death are covered in details. RESULTS AND CONCLUSION: Our results
propose a critical role of interleukin-17 producing cells in acute and chronic
inflammatory responses.
PMID- 27485025
TI - Moderate Humidity Delays Electron-Hole Recombination in Hybrid Organic-Inorganic
Perovskites: Time-Domain Ab Initio Simulations Rationalize Experiments.
AB - Experiments show both positive and negative changes in performance of hybrid
organic-inorganic perovskite solar cells upon exposure to moisture. Ab initio
nonadiabatic molecular dynamics reveals the influence of humidity on nonradiative
electron-hole recombination. In small amounts, water molecules perturb perovskite
surface and localize photoexcited electron close to the surface. Importantly,
deep electron traps are avoided. The electron-hole overlap decreases, and the
excited state lifetime increases. In large amounts, water forms stable hydrogen
bonded networks, has a higher barrier to enter perovskite, and produces little
impact on charge localization. At the same time, by contributing high frequency
polar vibrations, water molecules increase nonadiabatic coupling and accelerate
recombination. In general, short coherence between electron and hole benefits
photovoltaic response of the perovskites. The calculated recombination time
scales show excellent agreement with experiment. The time-domain atomistic
simulations reveal the microscopic effects of humidity on perovskite excited
state lifetimes and rationalize the conflicting experimental observations.
PMID- 27485027
TI - Stress and Humoral Innate Immune Response of Gilthead Seabream Sparus aurata
Cultured in Sea Cages.
AB - Innate and acquired immune responses of Gilthead Seabream Sparus aurata was
studied under normal culture and short-term stressful conditions for 18 months in
offshore sea cages in Alghero Bay, Italy. Every 45 d, 50 fish were sampled and
divided into two groups: fish in the first group (normal culture conditions) were
bled after harvesting; fish in the second group were put into a tank under
stressful conditions (crowding and confinement) and bled after 2 h. Innate
humoral immunity, such as complement-like, hemagglutination, and lysozyme
activities, was determined in the sera of both groups. Pathogen challenge was not
performed, but the specific humoral immune response was assessed against the most
common pathogens affecting cultured fish in Sardinia. Stressed fish, compared
with the control, showed a lower lysozyme activity against Vibrio (Listonella)
anguillarum, which was not clearly correlated with temperatures. Complement-like
activity differed between the first and second half of the study and, at the end
of the trial, a slightly higher activity was recorded in the controls than in the
stressed fish. Hemagglutination activity was mainly higher in the stressed fish
than in control fish. Confinement, crowding, and cold water temperature caused
decreased lysozyme activity in short-term stressed Gilthead Seabream compared
with those reared normally. The specific humoral immune response, against V.
anguillarum, Tenacibaculum mesophilum, Enterococcus Seriolicida, and Aeromonas
sobria, fluctuated during the rearing period, particularly during the first year
of culture. Received October 12, 2015; accepted March 24, 2016.
PMID- 27485026
TI - Notch signalling mediates reproductive constraint in the adult worker honeybee.
AB - The hallmark of eusociality is the reproductive division of labour, in which one
female caste reproduces, while reproduction is constrained in the subordinate
caste. In adult worker honeybees (Apis mellifera) reproductive constraint is
conditional: in the absence of the queen and brood, adult worker honeybees
activate their ovaries and lay haploid male eggs. Here, we demonstrate that
chemical inhibition of Notch signalling can overcome the repressive effect of
queen pheromone and promote ovary activity in adult worker honeybees. We show
that Notch signalling acts on the earliest stages of oogenesis and that the
removal of the queen corresponds with a loss of Notch protein in the germarium.
We conclude that the ancient and pleiotropic Notch signalling pathway has been co
opted into constraining reproduction in worker honeybees and we provide the first
molecular mechanism directly linking ovary activity in adult worker bees with the
presence of the queen.
PMID- 27485028
TI - The acute and temporary modulation of PERIOD genes by hydrocortisone in healthy
subjects.
AB - The physiological stress system and the circadian clock system communicate with
each other at different signaling levels. The steroid hormone cortisol, the end
effector of the hypothalamus-pituitary-adrenal axis, is released in response to
stress and acts as a mediator in circadian rhythms. We determined the effect of
escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3)
in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is
involved in the cortisol-mediated PERIOD gene expression. Forty participants (50%
males and 50% females) were randomly assigned to groups receiving a saline
placebo solution or 3 mg, 6 mg, 12 mg and 24 mg of hydrocortisone. Blood was
drawn every 15 min to measure quantitative gene expression of PER1, PER2 and
PER3. A potential role of the GR was determined by an ex vivo study stimulating
whole blood with hydrocortisone and RU486 (a GR antagonist). As a result,
moderate doses of hydrocortisone produced an acute and temporary induction of
PER1 and PER3 mRNA levels, whereas PER2 was not responsive to the hormone
administration. The cortisol-dependent induction of PER1 was blocked by the GR
antagonist in whole blood after treatment with hydrocortisone and RU486 ex vivo.
In conclusion, acute pharmacological stress modulated the expression of PER1 and
PER3 in whole blood temporarily in our short-term sampling design, suggesting
that these circadian genes mediate stable molecular mechanisms in the periphery.
PMID- 27485030
TI - Development of an Allergy Immunotherapy Leads to a New Type of Hepatitis B
Vaccine.
PMID- 27485031
TI - Genetic variation in photosynthetic performance and tolerance to osmotic stress
(desiccation, freezing, hyposalinity) in the rocky littoral foundation species
Fucus vesiculosus (Fucales, Phaeophyceae).
AB - Genetic diversity may play an analogous role to species diversity, as it can
contribute to ecosystem function and stability, and provision of ecosystem
services. In the Baltic Sea, perennial algal beds are often comprised of only
Fucus vesiculosus and the amount of genetic variation in fitness-related traits
(i.e., the ability of the alga to photosynthesize or withstand stress) will thus
determine the alga's local persistence in a changing environment. To study
genetic variation in the crucial traits behind persistence we grew replicate
vegetative branches that came from the same genotype in common gardens. We
quantified osmotic stress tolerance and recovery responses by exposing branches
to desiccation, freezing, and hyposalinity regimens. Our results show that
genetic variation among genotypes was apparent for some photosynthetic parameters
(maximal electron transport rate, saturation irradiance for electron transport,
nonphotochemical quenching) and growth. Algae tolerated freezing (1,440 min at
2.5 degrees C) and hyposalinity (1,560 min at 2.5) well, but did not recover from
desiccation (70 min at 12 degrees C, causing ~94% water loss). Furthermore, we
found very little if any evidence on genetic variation in tolerance to these
stressors. Our results suggest that low salinity and cold winters in the northern
marginal populations selected for hyposalinity and freezing tolerant genotypes,
possibly eroding genetic variation in tolerance, but that tolerance to harsh
desiccation has been lost, likely due to relaxed selection. The overall
availability of genetic variation in fitness related traits might be supportive
for F. vesiculosus during adaptation to gradual changes of its environment.
PMID- 27485029
TI - Creation of a model to predict survival in patients with refractory coeliac
disease using a multinational registry.
AB - BACKGROUND: Refractory coeliac disease is a severe complication of coeliac
disease with heterogeneous outcome. AIM: To create a prognostic model to estimate
survival of patients with refractory coeliac disease. METHODS: We evaluated
predictors of 5-year mortality using Cox proportional hazards regression on
subjects from a multinational registry. Bootstrap resampling was used to
internally validate the individual factors and overall model performance. The
mean of the estimated regression coefficients from 400 bootstrap models was used
to derive a risk score for 5-year mortality. RESULTS: The multinational cohort
was composed of 232 patients diagnosed with refractory coeliac disease across
seven centres (range of 11-63 cases per centre). The median age was 53 years and
150 (64%) were women. A total of 51 subjects died during a 5-year follow-up
(cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox
proportional hazards model, the following variables were significantly associated
with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year
increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal
intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin
(per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple
weighted three-factor risk score was created to estimate 5-year survival.
CONCLUSIONS: Using data from a multinational registry and previously reported
risk factors, we create a prognostic model to predict 5-year mortality among
patients with refractory coeliac disease. This new model may help clinicians to
guide treatment and follow-up.
PMID- 27485032
TI - Mono- and multimeric ferrocene congeners of quinoline-based polyamines as
potential antiparasitics.
AB - A series of mono- and multimeric polyamine-containing ferrocenyl complexes
containing a quinoline motif were prepared. The complexes were characterised by
standard techniques. The molecular structure of the monomeric salicylaldimine
derivative was elucidated using single crystal X-ray diffraction and was
consistent with the proposed structure. The antiplasmodial activity of the
compounds were evaluated in vitro against both the NF54 (chloroquine-sensitive)
and K1 (chloroquine-resistant) strains of Plasmodium falciparum. The polyamine
derivatives exhibit good resistance index values suggesting that these systems
are beneficial in overcoming the resistance experienced by chloroquine.
Mechanistic studies suggest that haemozoin formation may be the target of these
quinoline complexes in the parasite. Some of the complexes exhibit moderate to
high cytotoxicity against WHCO1 oesophageal cancer cells in vitro. The monomeric
ferrocenyl-amine complexes exhibit potent activity against this particular cell
line. The complexes were also screened against the G3 strain of Trichomonas
vaginalis and the salicylaldimine complexes demonstrated promising activity at
the tested concentration. All of these compounds show no inhibitory effect on
several common normal flora bacteria, indicative of their selectivity for
eukaryotic pathogens and cancer.
PMID- 27485034
TI - Psychologists Should Help Curb the Wave of U. S. Gun Violence.
PMID- 27485033
TI - Diffusion tensor imaging and histology of developing hearts.
AB - Diffusion tensor imaging (DTI) has emerged as a promising method for noninvasive
quantification of myocardial microstructure. However, the origin and behavior of
DTI measurements during myocardial normal development and remodeling remain
poorly understood. In this work, conventional and bicompartmental DTI in addition
to three-dimensional histological correlation were performed in a sheep model of
myocardial development from third trimester to postnatal 5 months of age.
Comparing the earliest time points in the third trimester with the postnatal 5
month group, the scalar transverse diffusivities preferentially increased in both
left ventricle (LV) and right ventricle (RV): secondary eigenvalues D2 increased
by 54% (LV) and 36% (RV), whereas tertiary eigenvalues D3 increased by 85% (LV)
and 67% (RV). The longitudinal diffusivity D1 changes were small, which led to a
decrease in fractional anisotropy by 41% (LV) and 33% (RV) in 5 month versus
fetal hearts. Histological analysis suggested that myocardial development is
associated with hyperplasia in the early stages of the third trimester followed
by myocyte growth in the later stages up to 5 months of age (increased average
myocyte width by 198%, myocyte length by 128%, and decreased nucleus density by
70% between preterm and postnatal 5 month hearts.) In a few histological samples
(N = 6), correlations were observed between DTI longitudinal diffusivity and
myocyte length (r = 0.86, P < 0.05), and transverse diffusivity and myocyte width
(r = 0.96, P < 0.01). Linear regression analysis showed that transverse
diffusivities are more affected by changes in myocyte size and nucleus density
changes than longitudinal diffusivities, which is consistent with predictions of
classical models of diffusion in porous media. Furthermore, primary and secondary
DTI eigenvectors during development changed significantly. Collectively, the
findings demonstrate a role for DTI to monitor and quantify myocardial
development, and potentially cardiac disease. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27485035
TI - Specific alleles at immune genes, rather than genome-wide heterozygosity, are
related to immunity and survival in the critically endangered Attwater's prairie
chicken.
AB - The negative effects of inbreeding on fitness are serious concerns for
populations of endangered species. Reduced fitness has been associated with lower
genome-wide heterozygosity and immune gene diversity in the wild; however, it is
rare that both types of genetic measures are included in the same study. Thus, it
is often unclear whether the variation in fitness is due to the general effects
of inbreeding, immunity-related genes or both. Here, we tested whether genome
wide heterozygosity (20 990 SNPs) and diversity at nine immune genes were better
predictors of two measures of fitness (immune response and survival) in the
endangered Attwater's prairie-chicken (Tympanuchus cupido attwateri). We found
that postrelease survival of captive-bred birds was related to alleles of the
innate (Toll-like receptors, TLRs) and adaptive (major histocompatibility
complex, MHC) immune systems, but not to genome-wide heterozygosity. Likewise, we
found that the immune response at the time of release was related to TLR and MHC
alleles, and not to genome-wide heterozygosity. Overall, this study demonstrates
that immune genes may serve as important genetic markers when monitoring fitness
in inbred populations and that in some populations specific functional genes may
be better predictors of fitness than genome-wide heterozygosity.
PMID- 27485036
TI - Genome-wide identification and gene expression profiling of ubiquitin ligases for
endoplasmic reticulum protein degradation.
AB - Endoplasmic reticulum (ER)-associated degradation (ERAD) is a mechanism by which
unfolded proteins that accumulate in the ER are transported to the cytosol for
ubiquitin-proteasome-mediated degradation. Ubiquitin ligases (E3s) are a group of
enzymes responsible for substrate selectivity and ubiquitin chain formation. The
purpose of this study was to identify novel E3s involved in ERAD. Thirty-seven
candidate genes were selected by searches for proteins with RING-finger motifs
and transmembrane regions, which are the major features of ERAD E3s. We performed
gene expression profiling for the identified E3s in human and mouse tissues.
Several genes were specifically or selectively expressed in both tissues; the
expression of four genes (RNFT1, RNF185, CGRRF1 and RNF19B) was significantly
upregulated by ER stress. To determine the involvement of the ER stress
responsive genes in ERAD, we investigated their ER localisation, in vitro
autoubiquitination activity and ER stress resistance. All were partially
localised to the ER, whereas CGRRF1 did not possess E3 activity. RNFT1 and
RNF185, but not CGRRF1 and RNF19B, exhibited significant resistance to ER
stressor in an E3 activity-dependent manner. Thus, these genes are possible
candidates for ERAD E3s.
PMID- 27485038
TI - RBC omega-3 predicts risk for death.
PMID- 27485037
TI - OpEx - a validated, automated pipeline optimised for clinical exome sequence
analysis.
AB - We present an easy-to-use, open-source Optimised Exome analysis tool, OpEx
(http://icr.ac.uk/opex) that accurately detects small-scale variation, including
indels, to clinical standards. We evaluated OpEx performance with an
experimentally validated dataset (the ICR142 NGS validation series), a large 1000
exome dataset (the ICR1000 UK exome series), and a clinical proband-parent trio
dataset. The performance of OpEx for high-quality base substitutions and short
indels in both small and large datasets is excellent, with overall sensitivity of
95%, specificity of 97% and low false detection rate (FDR) of 3%. Depending on
the individual performance requirements the OpEx output allows one to optimise
the inevitable trade-offs between sensitivity and specificity. For example, in
the clinical setting one could permit a higher FDR and lower specificity to
maximise sensitivity. In contexts where experimental validation is not possible,
minimising the FDR and improving specificity may be a preferable trade-off for
slightly lower sensitivity. OpEx is simple to install and use; the whole pipeline
is run from a single command. OpEx is therefore well suited to the increasing
research and clinical laboratories undertaking exome sequencing, particularly
those without in-house dedicated bioinformatics expertise.
PMID- 27485039
TI - The sympathetic nervous system affects the susceptibility and course of
Trypanosoma cruzi infection.
AB - Trypanosoma cruzi (T. cruzi) is an intracellular parasite that causes Chagas'
disease, a major health problem in Latin America. Using a murine model of
infection with this parasite, we have previously shown that corticosterone blood
levels are markedly elevated during the course of the disease in C57Bl/6 male
mice and that this increase is protective for the host by restricting the
production of pro-inflammatory cytokines. Since the hypothalamus-pituitary
adrenal (HPA) axis usually operates in a concerted way with the sympathetic
nervous system (SNS), we have now studied whether noradrenergic nerves can affect
the course of T. cruzi infection and the sexual dimorphism observed in the
disease. We found a decreased splenic noradrenaline concentration and content,
paralleled by a reduction in noradrenergic nerve fibers in the spleen of infected
mice, and increased HPA axis activity. These alterations were more marked in
males than in females. When the spontaneous loss of noradrenergic nerve fibers
was advanced by chemical sympathectomy prior to infection, males died earlier and
mortality significantly increased in females. Chemical denervation did not
significantly affect the concentration of specific IgM and IgG2a antibodies to T.
cruzi, and did not worsen myocarditis, but resulted in increased parasitemia and
IL-6 and IFN-gamma blood levels. The results obtained in this model of parasitic
disease provide further indications of the relevance of interactions between the
immune system and the SNS for host defense.
PMID- 27485040
TI - beta-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2
spectrum.
AB - beta-Adrenergic signaling can regulate macrophage involvement in several diseases
and often produces anti-inflammatory properties in macrophages, which are similar
to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is
not clear that beta-adrenergic-stimulated macrophages may be classified strictly
as M2. In this in vitro study, we utilized recently published criteria and
transcriptome-wide bioinformatics methods to map the relative polarity of murine
beta-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results
show that beta-adrenergic-stimulated macrophages did not fit entirely into any
one pre-defined category of the M1-M2 spectrum but did express genes that are
representative of some M2 side categories. Moreover, transcript origin analysis
of genome-wide transcriptional profiles located beta-adrenergic-stimulated
macrophages firmly on the M2 side of the M1-M2 spectrum and found active
suppression of M1 side gene transcripts. The signal transduction pathways
involved were mapped through blocking experiments and bioinformatics analysis of
transcription factor binding motifs. M2-promoting effects were mediated
specifically through beta2-adrenergic receptors and were associated with CREB,
C/EBPbeta, and ATF transcription factor pathways but not with established M1-M2
STAT pathways. Thus, beta-adrenergic-signaling induces a macrophage transcriptome
that locates on the M2 side of the M1-M2 spectrum but likely accomplishes this
effect through a signaling pathway that is atypical for M2-spectrum macrophages.
PMID- 27485041
TI - Prevalence of hand syndromes among patients with diabetes mellitus in Taiwan: A
population-based study.
AB - BACKGROUND: Population-based data for diabetic hand syndrome (DHS) are limited.
The aim of the present epidemiological study was to estimate the overall and
cause-specific prevalence and rate ratio (RR) of DHS in patients with diabetes.
METHODS: The present study was a cross-sectional study based on a random sample
of 57 093 diabetics and matched controls, both identified from Taiwan National
Health Insurance claims in 2010. The DHS analyzed in the present study included
carpal tunnel syndrome (CTS), stenosing flexor tenosynovitis (SFT), limited joint
mobility (LJM), and Dupuytren's disease (DD). RESULTS: The prevalence of overall
DHS was estimated at 2472 per 105 for the diabetics, compared with 1641 per 105
for the controls, representing a prevalence RR of 1.51 (95 % confidence interval
[CI] 1.39-1.64). Stratified analyses further revealed that the significantly
increased prevalence of overall DHS was more evident in females than males (1.59
vs 1.36) and was only noted in diabetics aged >=35 years. Cause-specific analysis
suggested that patients with diabetes had the highest prevalence of CTS (1244 per
105 ), followed by SFT (1209 per 105 ), LJM (39 per 105 ), and DD (6 per 105 ).
In addition, diabetes was only significantly associated with CTS (RR 1.34; 95 %
CI 1.20-1.51) and SFT (1.74; 95 % CI 1.54-1.97). CONCLUSION: The prevalence of
overall and certain cause-specific DHS was significantly elevated in patients
with diabetes in Taiwan.
PMID- 27485042
TI - Diagnostic mistakes of culturally diverse individuals when using North American
neuropsychological tests.
AB - Although the role of culture has increasingly gained acceptance in clinical
neuropsychology, relatively minimal research exists regarding the actual impact
on clinical activities. In this study, we assess how using North American
neuropsychological tests affects diagnostic accuracy in cognitive disorders of
culturally diverse individuals. To address this question, participants from
Colombia, Morocco, and Spain were administered five commonly used
neuropsychological tests and the test results were used to determine whether they
would be classified as having the DSM-5 diagnostic criteria for Mild Cognitive
and Major Cognitive Disorder. Results reveal that diagnostic error occurred up to
20% of the time, and that the frequency of misdiagnosis differed by nationality.
These results provide evidence that using tests from one culture to assess
individuals from other cultures produces significant false positives. Findings
are discussed in terms of the foundations of neuropsychological assessment and
its relationship to cultural variables.
PMID- 27485043
TI - Apprehensive about retirement: Women, life transitions, and relationships.
AB - Understanding women's attitudes toward retirement is crucial for being able to
help women adjust to this transition. The present study uses interviews and
questionnaires to understand retirement ambivalence and the role that close
relationships play in women's retirement experiences. Findings indicate that
women have mixed feelings about retirement; they are both excited and fearful.
They particularly enjoy the freedom and control this transition brings but are
also moderately fearful of retirement, especially about shifting relationships. A
better-quality relationship correlates with greater satisfaction and less fear.
Such insights can be used to help women prepare for this major transition.
PMID- 27485044
TI - Regiodivergent Intermolecular [3+2] Cycloadditions of Vinyl Aziridines and
Allenes: Stereospecific Synthesis of Chiral Pyrrolidines.
AB - The first rhodium-catalyzed intermolecular [3+2] cycloaddition reaction of vinyl
aziridines and allenes for the synthesis of enantioenriched functionalized
pyrrolidines was realized. [3+2] cycloaddition with the proximal C=C bond of N
allenamides gave 3-methylene-pyrrolidines in high regio- and
diastereoselectivity, whereas, 2-methylene-pyrrolidines were obtained as the
major products by the cycloadditions of vinyl aziridines with the distal C=C bond
of allenes. Use of readily available starting materials, a broad substrate scope,
high selectivity, mild reaction conditions, as well as versatile
functionalization of the cycloadducts make this approach very practical and
attractive.
PMID- 27485045
TI - Anterior inferior cerebellar artery aneurysms: Segments and results of surgical
and endovascular managements.
AB - BACKGROUND: Anterior inferior cerebellar artery (AICA) aneurysms are rare and
published clinical experience with these aneurysms is limited. OBJECTIVE: The
objective of this article is to report angiographic characteristics and results
associated with premeatal, meatal and postmeatal segments, surgical and
endovascular therapies. METHODS: A literature review was performed through PubMed
using "anterior inferior cerebellar artery aneurysm" through January 2016.
Clinical data, angiograms, management techniques, and patient outcomes were
reviewed for 47 collected cases in 30 previous reports. RESULTS: Of these
aneurysms, 21 (44.7%) were associated with meatal segment, 10 (21.3%) were
postmeatal and 16 (34.0%) were premeatal. Patients with meatal aneurysms are more
likely to present with subarachnoid hemorrhage and hearing loss and facial palsy
(77.8%). Patient outcomes of meatal aneurysms presented with more neuropathies
(51.7%) and cerebellar symptoms (14.3%) (p = 0.049). Four cases of meatal
aneurysm with preoperative cranial nerve deficits (two VII and two VIII) showed
improvement after surgery. Endovascular treatment achieved outcomes similar to
surgical treatment (p = 0.327). CONCLUSIONS: AICA aneurysms have a predilection
for meatal segment. Patients with meatal aneurysms are more likely to present
with subarachnoid hemorrhage and hearing loss and facial palsy. Patient outcomes
of meatal aneurysms presented with more neuropathies and cerebellar symptoms.
Endovascular treatment achieved outcomes similar to surgical treatment.
PMID- 27485046
TI - Modification of cerebral vascular anatomy induced by Leo stent placement
depending on the site of stenting: A series of 102 cases.
AB - BACKGROUND AND PURPOSE: Recent studies demonstrated the capacity of stents to
modify cerebral vascular anatomy. This study evaluates arterial anatomy
deformation after Leo stent placement according to the stenting site and the
impact on the immediate postoperative and six-month degree of aneurysmal
occlusion. MATERIALS AND METHODS: A total of 102 stents were placed against the
neck of aneurysms situated in the anterior cerebral circulation. Aneurysms were
classified into two groups: The first was called the distal group (n = 62) and
comprised aneurysms situated in the middle cerebral and anterior communicating
arteries and the second was called the proximal group (n = 40) and comprised
aneurysms in other sites. The stented arterial segment was classified as deformed
or non-deformed by blinded review and superimposition of anonymised films before
and after stenting. The degree of occlusion was determined immediately
postoperatively and at six months. RESULTS: Significantly, anatomical deformity
was observed in the distal group compared to the proximal group (85% vs 28%). No
significant difference was observed between the two groups in terms of
postoperative degree of occlusion. At six months, a significant difference was
observed between the two groups: three recurrences in the distal group vs 10
recurrences in the proximal group. Two (3%) recurrences were observed in the
deformed group vs 11 (31%) recurrences in the non-deformed group. CONCLUSIONS:
Arterial deformity induced by stenting is even more marked for distal aneurysms.
The recurrence rate is smaller when the stent placement results in an arterial
anatomical change. The percentage of recurrence is lower when anatomy was amended
by stent implantation.
PMID- 27485047
TI - Rational approach, technique and selection criteria treating lumbar disk
herniations by oxygen-ozone therapy.
AB - Radicular lumbar back pain is an important public health problem not yet
benefiting from a unequivocal treatment approach. Medical and physical therapies
represent the first solution; however, when these fail, the second therapeutic
step is still controversial and mini-invasive treatments may play an important
role. In these cases oxygen-ozone therapy has been proved to be a very safe and
effective option that is widely used with different modalities. This paper, by
reviewing oxygen-ozone therapy literature data, aims to describe the rationale of
oxygen-ozone therapy for the treatment of lumbar disk herniations, propose an
effective procedural technique and clarify patient selection criteria;
furthermore, complications and follow-up management are also considered.
PMID- 27485048
TI - Large basilar perforator pseudoaneurysm: A case report.
AB - Basilar perforator aneurysms are rare and a communication between a basilar
perforator and a separate pseudoaneurysm cavity is extremely rare. We describe a
case presenting with high grade subarachnoid hemorrhage which on further
investigation delineated a 2-3 mm dissecting basilar perforator aneurysm
communicating superiorly into a contained 6 mm pseudoaneurysm cavity. This case
illustrates an unusual neurovascular pathology with low potential for successful
endovascular treatment such as coil embolization or intracranial flow diverter
stenting. Conservative medical management remains the main stay of treatment for
such poor surgical candidates.
PMID- 27485049
TI - The sense of body ownership relaxes temporal constraints for multisensory
integration.
AB - Experimental work on body ownership illusions showed how simple multisensory
manipulation can generate the illusory experience of an artificial limb as being
part of the own-body. This work highlighted how own-body perception relies on a
plastic brain representation emerging from multisensory integration. The
flexibility of this representation is reflected in the short-term modulations of
physiological states and perceptual processing observed during these illusions.
Here, we explore the impact of ownership illusions on the temporal dimension of
multisensory integration. We show that, during the illusion, the temporal window
for integrating touch on the physical body with touch seen on a virtual body
representation, increases with respect to integration with visual events seen
close but separated from the virtual body. We show that this effect is mediated
by the ownership illusion. Crucially, the temporal window for visuotactile
integration was positively correlated with participants' scores rating the
illusory experience of owning the virtual body and touching the object seen in
contact with it. Our results corroborate the recently proposed causal inference
mechanism for illusory body ownership. As a novelty, they show that the ensuing
illusory causal binding between stimuli from the real and fake body relaxes
constraints for the integration of bodily signals.
PMID- 27485051
TI - Secular trends in physical fitness and body size in Lithuanian children and
adolescents between 1992 and 2012.
AB - BACKGROUND AND METHODS: There is a paucity of data on contemporary secular trends
on the different aspects of physical fitness in school-aged children and
adolescents. This study presents the largest ever data set on changes in fitness
between 1992, 2002 and 2012 for both genders of schoolchildren aged 11-18 years
(n=16 199). Eurofit test battery was used to assess the balance, flexibility,
muscular strength and power, agility and cardiorespiratory fitness.
Anthropometrics were also measured and body mass index (BMI) was calculated.
RESULTS: The study has shown loss of flexibility, leg muscle power, upper body
strength and cardiorespiratory fitness between 1992 and 2012, although there was
an improvement in abdominal muscle strength in girls, agility in boys and balance
in both genders during the same period. At large, negative trends in aspects of
fitness seen between 1992 and 2002 have not slowed down between 2002 and 2012.
Positive trends in agility and abdominal muscle strength seen before 2002 have
regressed or were reversed between 2002 and 2012, while balance continued to
improve at increased pace. While the BMI continued to increase in all groups,
analysis of covariance has shown that it was not the main cause of changes in
fitness. CONCLUSIONS: The general decline in physical fitness in Lithuanian
schoolchildren observed between 1992 and 2002 continued between 2002 and 2012,
although some aspects of fitness showed a positive trend. If this general
negative trend continues, it will compromise the well-being of future adults and
create a serious economic burden on the society.
PMID- 27485050
TI - Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary
analysis of the mothers, omega-3, and mental health study.
AB - BACKGROUND: Vitamin D insufficiency may be associated with depressive symptoms in
non-pregnant adults. We performed this study to evaluate whether low maternal
vitamin D levels are associated with depressive symptoms in pregnancy. METHODS:
This study was a secondary analysis of a randomized trial designed to assess
whether prenatal omega-3 fatty acid supplementation would prevent depressive
symptoms. Pregnant women from Michigan who were at risk for depression based on
Edinburgh Postnatal Depression Scale Score or history of depression were
enrolled. Participants completed the Beck Depression Inventory (BDI) and Mini
International Neuropsychiatric Interview at 12-20 weeks, 26-28 weeks, 34-36
weeks, and 6-8 weeks postpartum. Vitamin D levels were measured at 12-20 weeks (N
= 117) and 34-36 weeks (N = 112). Complete datasets were available on 105
subjects. Using regression analyses, we evaluated the relationship between
vitamin D levels with BDI scores as well as with MINI diagnoses of major
depressive disorder and generalized anxiety disorder. Our primary outcome measure
was the association of maternal vitamin D levels with BDI scores during early and
late pregnancy and postpartum. RESULTS: We found that vitamin D levels at 12-20
weeks were inversely associated with BDI scores both at 12-20 and at 34-36 weeks'
gestation (P < 0.05, both). For every one unit increase in vitamin D in early
pregnancy, the average decrease in the mean BDI score was .14 units. Vitamin D
levels were not associated with diagnoses of major depressive disorder or
generalized anxiety disorder. CONCLUSIONS: In women at risk for depression, early
pregnancy low vitamin D levels are associated with higher depressive symptom
scores in early and late pregnancy. Future investigations should study whether
vitamin D supplementation in early pregnancy may prevent perinatal depressive
symptoms. TRIAL REGISTRATION: https://clinicaltrials.gov/ REGISTRATION NUMBER:
NCT00711971.
PMID- 27485052
TI - Competing risk analysis of factors related to long-term incidence of CHD.
AB - BACKGROUND: The 5-year follow-up results for the 1202 middle-aged men prospective
study of coronary heart disease (CHD) incidence were published in 1980. This
paper extends the follow-up, relating the development of CHD to 10 risk factors.
METHODS: The population studied comprised all men born in the 10-year period 1909
1918 aged 45-64 years at baseline who were registered in 6 group practices in
Belfast. Some 1202 CHD-free men entered the study. Study end points included: (a)
the development of CHD, (b) the development of myocardial infarction, (c) the
development of angina pectoris, (d) death from myocardial infarction and (e)
death from other causes. The men were followed for an average of 6.9 years, and
the influence of 10 risk factors was assessed by Cox's proportional hazards model
in a competing risk framework. RESULTS: The analysis of first major CHD event
identified four risk factors-diastolic blood pressure, serum cholesterol, T wave
abnormality and tobacco index. First myocardial infarction depended on diastolic
blood pressure, ST abnormality and tobacco index, while time to first angina
pectoris depended on serum cholesterol, T abnormality, tobacco index and age at
entry. These findings do not support the hypothesis of a common risk factor
profile in the myocardial infarction and angina pectoris groups. The sensitivity
of all models was poor. DISCUSSION: The study confirms the role of known risk
factors in the development of first CHD event. It also suggests that the risk
factors involved in developing myocardial infarction and angina pectoris differ.
The poor sensitivity of models suggests the presence of unmeasured risk factors
in the aetiology of CHD.
PMID- 27485053
TI - Recent cohort effects in suicide in Scotland: a legacy of the 1980s?
AB - BACKGROUND: Mortality rates are higher in Scotland relative to England and Wales,
even after accounting for deprivation. This 'excess' mortality is partly due to
higher mortality from alcohol-related and drug-related deaths, violence and
suicide (particularly in young adults). This study investigated whether cohort
effects from exposure to neoliberal politics from the 1980s might explain the
recent trends in suicide in Scotland. METHODS: We analysed suicide deaths data
from 1974 to 2013 by sex and deprivation using shaded contour plots and intrinsic
estimator regression modelling to identify and quantify relative age, period and
cohort effects. RESULTS: Suicide was most common in young adults (aged around 25
40 years) living in deprived areas, with a younger peak in men. The peak age for
suicide fell around 1990, especially for men for whom it dropped quickly from
around 50 to 30 years. There was evidence of an increased risk of suicide for the
cohort born between 1960 and 1980, especially among men living in the most
deprived areas (of around 30%). The cohort at highest risk occurred earlier in
the most deprived areas, 1965-1969 compared with 1970-1974. CONCLUSIONS: The risk
of suicide increased in Scotland for those born between 1960 and 1980, especially
for men living in the most deprived areas, which resulted in a rise in age
standardised rates for suicide among young adults during the 1990s. This is
consistent with the hypothesis that exposure to neoliberal politics created a
delayed negative health impact.
PMID- 27485054
TI - Association between targeted somatic mutation (TSM) signatures and HGS-OvCa
progression.
AB - Evidence already exists that the activation-induced cytidine deaminase
(AID/APOBEC) and the adenosine deaminase (ADAR) families of enzymes are
implicated as powerful mutagens in oncogenic processes in many somatic tissues.
Each deaminase is identified by the DNA or RNA nucleotide sequence ("motif")
surrounding the nucleotide targeted for deamination. The primary objective of
this study is to develop an in silico approach to identify nucleotide sequence
changes of the target motifs of key deaminases during oncogenesis. If successful,
a secondary objective is to investigate if such changes are associated with
disease progression indicators that include disease stage and progression-free
survival time. Using a discovery cohort of 194 high-grade serous ovarian
adenocarcinoma (HGS-OvCa) exomes, the results confirm the ability of the novel in
silico approach used to identify changes in the preferred target motifs for AID,
APOBEC3G, APOBEC3B, and ADAR1 during oncogenesis. Using this approach, a set of
new cancer-progression associated signatures (C-PASs) were identified.
Furthermore, it was found that the C-PAS identified can be used to differentiate
between the cohort of patients that remained progression-free for longer than 60
months, from those in which disease progressed within 60 months (sensitivity 95%,
specificity 90%). The spectrum of outcomes observed here could provide a
foundation for future clinical assessment of susceptibility variants in ovarian,
and several other cancers as disease progresses. The ability of the in silico
methodology used to identify changes in deaminase motifs during oncogenesis also
suggests new links between immune system function and tumorigenesis.
PMID- 27485056
TI - Hepatic resection for metastatic breast cancer: an exercise in selection bias.
PMID- 27485055
TI - Visual Outcome and Related Factors in Bilateral Total Congenital Cataract
Patients: A Prospective Cohort Study.
AB - This study is to evaluate the visual outcome and identify its crucial related
factors in children undergoing cataract surgery for bilateral total congenital
cataract (CC). This prospective study included consecutive bilateral total
cataract patients undergoing primary surgery at Zhongshan Ophthalmic Center
(ZOC), Guangzhou, China from Jan 2010 to May 2014. Visual outcome was estimated
by best-corrected visual acuity (BCVA) at last follow-up. Potential related
factors, including gender, age at last follow-up, age at primary surgery,
surgical procedure, postoperative complications (PCs), frequency of follow-up and
changes in spectacles were evaluated. Eighty-eight children (176 eyes) were
included in the cohort. The mean post-operative BCVA (logMAR) was 1.07 +/- 0.53
at the mean follow-up duration 31.07 +/- 19.36 months. Multivariable generalized
estimating equations (GEEs) showed BCVA was significantly associated with PCs,
age at last follow-up and age at primary surgery. Partial correlation analysis
indicated age at primary surgery was positively correlated with BCVA controlling
for the other factors, both for the whole age range (R = 0.415, P < 0.001) and
age >6 months (R = 0.867, P < 0.001). Better visual acuity was related to early
primary surgery and low PC occurrence in children with bilateral total CC. Timely
surgical intervention and strict control of PCs would be potential steps to
achieving better visual outcome.
PMID- 27485057
TI - Positive para-aortic lymph nodes following pancreatectomy for pancreatic cancer.
Systematic review and meta-analysis of impact on short term survival and
association with clinicopathologic features.
AB - BACKGROUND: The relation between para-aortic lymph nodes (PALN) involvement and
pancreatic ductal adenocarcinoma (PDAC) survival, along with the optimal handling
of this particular lymph node station remain unclear. A systematic review and
meta-analysis was performed to assess this. METHODS: A search of Medline, Embase,
Ovid and Cochrane databases was performed until July 2015 to identify studies
reporting on the relation of PALN involvement and PDAC outcomes and a meta
analysis was performed following data extraction. RESULTS: Ten retrospective
studies and two prospective non randomized studies (2467 patients) were included.
Patients with positive PALN had worse one (p < 0.00001) and two year (p <
0.00001) survival when compared with patients with negative PALN. Even when
comparing only patients with positive lymph nodes (N1), patients with PALN
involvement presented with a significant lower one (p = 0.03) and two (p = 0.002)
year survival. PALN involvement was associated with an increased possibility of
positive margin (R1) resection (p < 0.00001), stations' 12, 14 and 17 malignant
infiltration (p < 0.00001), but not with tumour stage (p = 0.78). DISCUSSION:
Involvement of PALN is associated with decreased survival in pancreatic cancer
patients. However, existence of long term survivors among this subgroup of
patients should be further evaluated, in order to identify factors associated
with their favourable prognosis.
PMID- 27485058
TI - Defining post-operative pancreatitis as a new pancreatic specific complication
following pancreatic resection.
AB - INTRODUCTION: Post-operative pancreatic fistula has been well defined. However
the underlying aetiology remains poorly understood. The aim of this review was to
investigate whether the underlying aetiology for a proportion of patients
suffering from post-operative pancreatic fistula was due to post-operative
pancreatitis. METHOD: A systematic literature review according to the PRISMA
guidelines. The date range was from 2005 to 2016. The search strategy included
the terms: post-operative pancreatitis, pathophysiology, post-operative
pancreatic fistula, pancreaticoduodenectomy, ischaemic pancreatitis,
microcirculation and pancreatitis, serum and drain amylase and lipase. The data
was summarised without quantitative or qualitative analysis. RESULTS: There
exists significant physiological, biochemical, clinical and histological evidence
in the literature that a proportion of post-operative pancreatic fistula is due
to post-operative pancreatitis. A new definition of post-operative pancreatitis
based on the presence of biochemical evidence for pancreatic inflammation
(urinary trypsinogen-2 >50 ug/L or serum amylase/lipase > upper limit of normal)
between post-operative days 0-2. Predicted severity is based on C-reactive
protein with a cut-off of 180 mg/L at post-operative day 2. The proposed grading
of severity is in line with previous work by international study group of
pancreatic surgery. CONCLUSION: Post-operative pancreatitis should be recognised
as a separate pancreatic specific complication following pancreatic resection.
Improved recognition may allow better understanding of potential methods of
prevention, treatment and prediction of severity.
PMID- 27485060
TI - Effects of Rowachol on prevention of postcholecystectomy pain after laparoscopic
cholecystectomy: prospective multicenter randomized controlled trial.
AB - BACKGROUND: Postcholecystectomy pain (PCP) is characterized by abdominal pain
after cholecystectomy. However, prevention of PCP is not well known yet. The
purpose of this study was to determine whether Rowachol might be useful in
preventing PCP. METHODS: Between May 2013 and January 2014, a total of 138
patients with gallbladder disease who were scheduled to undergo laparoscopic
cholecystectomy were randomly assigned to orally receive 100 mg Rowachol or
placebo three times daily for 3 months after surgery. Abdominal pain was assessed
using the European Organization for Research and Treatment of Cancer QLQ-C30
questionnaire. RESULTS: Incidence of PCP in the placebo group (n = 9, 14.3%) was
higher than that in the Rowachol group (n = 3, 4.7%) with statistically marginal
significance (P = 0.08). Risk factor analysis implicated PCP with increased
difficulty in performing LC, more frequent pathology with acute cholecystitis,
and absence of postoperative Rowachol treatment. Multivariate analysis revealed
that greater difficulty of laparoscopic cholecystectomy (HR = 5.78, 95% CI 1.36
24.40, P < 0.05), and absence of postoperative Rowachol treatment (HR = 2.54, 95%
CI 1.10-10.39, P < 0.05) were independent risk factors for development of PCP.
CONCLUSION: Rowachol might be beneficial for prevention of PCP after laparoscopic
cholecystectomy.
PMID- 27485059
TI - Systematic review of peri-operative prognostic biomarkers in pancreatic ductal
adenocarcinoma.
AB - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated
with a poor prognosis. This systematic review aimed to summarize the literature
regarding potential prognostic biomarkers to facilitate validation studies and
clinical application. METHODS: A systematic review was performed (2004-2014)
according to PRISMA guidelines. Studies were ranked using REMARK criteria and the
following outcomes were examined: overall/disease free survival, nodal
involvement, tumour characteristics, metastasis, recurrence and resectability.
RESULTS: 256 biomarkers were identified in 158 studies. 171 biomarkers were
assessed with respect to overall survival: urokinase-type plasminogen activator
receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers
were assessed for disease free survival: CD24 and S100A4 were the highest
ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and
FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin
and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for
metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed
resectability: sCD40L, s100a2, Ca 19-9, CEA. CONCLUSION: This review has
identified and ranked specific biomarkers that should be a primary focus of
ongoing validation and clinical translational work in PDAC.
PMID- 27485061
TI - Early surgical bypass versus endoscopic stent placement in pancreatic cancer.
AB - INTRODUCTION: The optimal treatment for biliary obstruction in pancreatic cancer
remains controversial between surgical bypass and endoscopic stenting. METHODS:
Retrospective analysis of unresected pancreatic cancer patients in the Healthcare
Cost and Utilization Project Florida State Inpatient and Ambulatory Surgery
databases (2007-2011). Propensity score matching by procedure. Primary outcome
was reintervention, and secondary outcomes were readmission, overall length of
stay (LOS), discharge home, death and cost. Multivariate analyses performed by
logistic regression. RESULTS: In a matched cohort of 622, 20.3% (63) of
endoscopic and 4.5% (14) of surgical patients underwent reintervention (p <
0.0001) and 56.0% (174) vs. 60.1% (187) were readmitted (p = 0.2909). Endoscopic
patients had lower median LOS (10 vs. 19 days, p < 0.0001) and cost ($21,648 vs.
$38,106, p < 0.0001) as well as increased discharge home (p = 0.0029). No
difference in mortality on index admission. On multivariate analysis, initial
procedure not predictive of readmission (p = 0.1406), but early surgical bypass
associated with lower odds of reintervention (OR = 0.233, 95% CI 0.119, 0.434).
DISCUSSION: Among propensity score-matched patients receiving bypass vs.
stenting, readmission and mortality rates are similar. However, candidates for
both techniques may experience fewer subsequent procedures if offered early
biliary bypass with the caveats of decreased discharge home and increased
cost/LOS.
PMID- 27485062
TI - Evaluating the risk of hepatocellular carcinoma in patients with prominently
elevated liver stiffness measurements by FibroScan: a multicentre study.
AB - BACKGROUND AND AIMS: There are limited data on the significance of liver
stiffness measurements (LSM) by transient elastography in the upper extreme end
of the measurable spectrum. This multicentre retrospective observational study
evaluated the risk of hepatocellular carcinoma (HCC) in patients with LSM >=20
kPa. METHODS: 432 cirrhosis patients with LSM >=20 kPa between June 2007 and
October 2015 were retrospectively followed-up through electronic records.
RESULTS: A minimum 1-year follow-up was available for 278 patients (177 men;
average age 57, range 18-84). LSM ranged from 20.0 to 75.0 kPa (mean 34.6 kPa).
Cumulative incidences of HCC were 19 (6.8%), 30 (10.8%) and 41 (14.7%) at 1, 2
and 3 years, respectively. HCC was associated with age (p = 0.003), higher LSM (p
= 0.005) and viral aetiology (p = 0.007). Patients were divided into 4 groups
based on LSM at entry: 20-25 kPa (n = 74); 25-30 kPa (n = 62); 30-40 kPa (n =
75); >40 kPa (n = 67). Compared to the 20-25 kPa group, the 30-40 kPa group had a
hazard ratio (HR) of 3.0 (95% CI, 1.1-8.3; p = 0.037), and the >40 kPa group had
a HR of 4.8 (95% CI, 1.7-13.4; p = 0.003). CONCLUSIONS: This study shows an
association between LSM at the upper extreme and HCC risk. Physicians may find
this beneficial as a non-invasive dynamic approach to assessing HCC risk in
cirrhosis patients.
PMID- 27485063
TI - Sequential transarterial chemoembolization and portal vein embolization before
resection is a valid oncological strategy for unilobar hepatocellular carcinoma
regardless of the tumor burden.
AB - OBJECTIVE: To investigate the long-term oncological outcome of patients with
resectable hepatocellular carcinoma (HCC) undergoing sequential transarterial
chemoembolization (TACE) and portal vein embolization (PVE). METHODS: Analysis of
all Child A HCC patients who underwent TACE-PVE before major liver resection from
2006 to 2012 was performed according to whether or not they underwent surgical
resection as planned. RESULTS: 54 patients (50 men, 93% median 69-years (range 44
87)) were included. Thirty-nine (72%) patients underwent resection, including
19/25, 16/23, and 4/6 of patients with BCLC A, B, and C (p = 0.839). Twenty-two
(56%) had tumor recurrence (median delay 10 months) including 9/19, 11/16, and
2/4 of the patients with BCLC A, B, and C (p = 0.430). Survival was significantly
better in resected patients as compared to those who were not resected (median
overall survival (OS): 44 vs. 18 months; p < 0.001). Recurrence was associated
with a poorer prognosis as compared to patients without recurrence (median OS 43
months vs. not reached; p < 0.001). BCLC stage did not influence survival (p =
0.13). CONCLUSION: In patients with large unilobar HCC, TACE-PVE leads to
resection in most patients, with a good oncological outcome regardless of the
tumor burden. When this strategy fails, patients can be managed with TACE despite
prior PVE.
PMID- 27485064
TI - Liver function declines with increased age.
AB - INTRODUCTION: Age itself is not considered a contraindication for high impact
surgery. However, the aging process of the liver remains largely unknown. This
study evaluates age-dependent changes in liver function using a quantitative
liver function test. METHODS: Between January 2005 and December 2014, 508
patients underwent (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) for the
assessment of liver function. These included 203 patients with healthy livers
(group A) and 57 patients with HCC and Child-Pugh A (group B). (99m)Tc-mebrofenin
uptake-rate of the whole liver corrected for body surface area (cMUR) was
calculated for all patients. Linear regression analysis was performed to assess
the relationship between age and cMUR. RESULTS: The mean cMUR was 8.50 +/-
2.05%/min/m(2) and 6.94 +/- 2.03%/min/m(2) in group A and B, respectively. A
negative linear correlation was found between patient's age and cMUR in group A,
r = 0.244, p = 0.000. In group B, there was no correlation between age and cMUR,
however, a trend in decline of liver function with age was noted. CONCLUSION:
This study shows that liver function deteriorates with age. Since the
regenerative capacity of the liver correlates with liver function, this finding
should be taken into account when assessing surgical risk in patients considered
for major liver resection.
PMID- 27485065
TI - Trends in the scientific program of the Americas Hepato-Pancreato-Biliary
Association (AHPBA) Annual Meeting over the past decade: the more things change,
the more they stay the same.
AB - BACKGROUND: Numerous clinical and basic science innovations have been presented
at the AHPBA. The objective was to define changes in content and methodology of
the scientific program over the past decade. METHODS: AHPBA abstracts from the
past 10-years were reviewed by 2 investigators (volume, content, origin,
methodology). RESULTS: Of 2194 total AHPBA abstracts (2005-2015), the volume per
year decreased over time (2005 = 283; 2015 = 177; p < 0.05). Contribution from
the United States increased (USA = 65% (41-76%); p < 0.05). Topic categories were
consistent across years (liver = 38% (30-46%), pancreas = 29% (27-48%), biliary =
13% (5-16%); p > 0.05). Amongst liver topics, primary tumors increased in volume
(13% (8-18%)). Colorectal metastases were stable (19% (15-28%)) but more frequent
than primary hepatic tumors overall (p < 0.05). Amongst pancreas topics, cancer
and cysts increased significantly (30% (18-39%) and 4% (0-5%) respectively).
While transplantation topics decreased (7% (3-12%), education abstracts increased
(1% (0-3%; p < 0.05). Retrospective methodology was consistent amongst 83% (75
91%) of abstracts despite a decrease in prospective studies (9% (3-17%; p <
0.05). Basic science (11% (4-15%)) topics decreased, while large
registry/database (9% (0-23%)) abstracts increased (p < 0.05). DISCUSSION:
Abstracts related to primary hepatic tumors, pancreatic cancer, pancreatic cystic
neoplasms, and education have increased over the past decade of the AHPBA. The
decrease in prospective methodology combined with few randomized trials remains
concerning.
PMID- 27485066
TI - The role of liver-directed surgery in patients with hepatic metastasis from
primary breast cancer: a multi-institutional analysis.
AB - BACKGROUND: Data on surgical management of breast liver metastasis are limited.
We sought to determine the safety and long-term outcome of patients undergoing
hepatic resection of breast cancer liver metastases (BCLM). METHODS: Using a
multi-institutional, international database, 131 patients who underwent surgery
for BCLM between 1980 and 2014 were identified. Clinicopathologic and outcome
data were collected and analyzed. RESULTS: Median tumor size of the primary
breast cancer was 2.5 cm (IQR: 2.0-3.2); 58 (59.8%) patients had primary tumor
nodal metastasis. The median time from diagnosis of breast cancer to
metastasectomy was 34 months (IQR: 16.8-61.3). The mean size of the largest liver
lesion was 3.0 cm (2.0-5.0); half of patients (52.0%) had a solitary metastasis.
An R0 resection was achieved in most cases (90.8%). Postoperative morbidity and
mortality were 22.8% and 0%, respectively. Median and 3-year overall-survival was
53.4 months and 75.2%, respectively. On multivariable analysis, positive surgical
margin (HR 3.57, 95% CI 1.40-9.16; p = 0.008) and diameter of the BCLM (HR 1.03,
95% CI 1.01-1.06; p = 0.002) remained associated with worse OS. DISCUSSION: In
selected patients, resection of breast cancer liver metastases can be done safely
and a subset of patients may derive a relatively long survival, especially from a
margin negative resection.
PMID- 27485069
TI - Scotopic vision in the monkey is modulated by the G protein-coupled receptor 55.
AB - The endogenous cannabinoid system plays important roles in the retina of mice and
monkeys via their classic CB1 and CB2 receptors. We have previously reported that
the G protein-coupled receptor 55 (GPR55), a putative cannabinoid receptor, is
exclusively expressed in rod photoreceptors in the monkey retina, suggesting its
possible role in scotopic vision. To test this hypothesis, we recorded full-field
electroretinograms (ERGs) after the intravitreal injection of the GPR55 agonist
lysophosphatidylglucoside (LPG) or the selective GPR55 antagonist CID16020046
(CID), under light- and dark-adapted conditions. Thirteen vervet monkeys
(Chlorocebus sabaeus) were used in this study: four controls (injected with the
vehicle dimethyl sulfoxide, DMSO), four injected with LPG and five with CID. We
analyzed amplitudes and latencies of the a-wave (photoreceptor responses) and the
b-wave (rod and cone system responses) of the ERG. Our results showed that after
injection of LPG, the amplitude of the scotopic b-wave was significantly higher,
whereas after the injection of CID, it was significantly decreased, compared to
the vehicle (DMSO). On the other hand, the a-wave amplitude, and the a-wave and b
wave latencies, of the scotopic ERG responses were not significantly affected by
the injection of either compound. Furthermore, the photopic ERG waveforms were
not affected by either drug. These results support the hypothesis that GPR55
plays an instrumental role in mediating scotopic vision.
PMID- 27485070
TI - The S-curve for forecasting waste generation in construction projects.
AB - Forecasting construction waste generation is the yardstick of any effort by
policy-makers, researchers, practitioners and the like to manage construction and
demolition (C&D) waste. This paper develops and tests an S-curve model to
indicate accumulative waste generation as a project progresses. Using 37,148
disposal records generated from 138 building projects in Hong Kong in four
consecutive years from January 2011 to June 2015, a wide range of potential S
curve models are examined, and as a result, the formula that best fits the
historical data set is found. The S-curve model is then further linked to project
characteristics using artificial neural networks (ANNs) so that it can be used to
forecast waste generation in future construction projects. It was found that,
among the S-curve models, cumulative logistic distribution is the best formula to
fit the historical data. Meanwhile, contract sum, location, public-private
nature, and duration can be used to forecast construction waste generation. The
study provides contractors with not only an S-curve model to forecast overall
waste generation before a project commences, but also with a detailed baseline to
benchmark and manage waste during the course of construction. The major
contribution of this paper is to the body of knowledge in the field of
construction waste generation forecasting. By examining it with an S-curve model,
the study elevates construction waste management to a level equivalent to project
cost management where the model has already been readily accepted as a standard
tool.
PMID- 27485071
TI - Chimeric antigen receptor-engineered primary natural killer cells: a tool to
improve adoptive tumor immunotherapy.
PMID- 27485072
TI - Research progress in the field of immunotherapeutic vaccination in human TB and
the way ahead.
PMID- 27485073
TI - Self-administered hyaluronidase-facilitated subcutaneous immunoglobulin therapy
in complicated primary antibody deficiencies.
AB - Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIg) is a new
immunoglobulin product for replacement therapy in patients with primary antibody
deficiencies (PAD). The pre-administration of recombinant human hyaluronidase
associated with 10% immunoglobulin allowed the infusion of larger (up to 600 ml)
amounts of immunoglobulin at a single infusion site, enabling patients to receive
the necessary treatment in a single monthly dose. Here, we report the
effectiveness and the tolerability of fSCIg in patients with severe PAD-related
comorbidities: refractory autoimmune thrombocytopenia; systemic granulomatous
disease; severe enteropathy, and Type I diabetes. We conclude that fSCIg could be
a feasible option to improve the adherence to replacement therapy also by
patients with severe PAD.
PMID- 27485074
TI - Cytokine-induced killer cell therapy-associated idiopathic thrombocytopenic
purpura: rare but noteworthy.
AB - Idiopathic thrombocytopenic purpura (ITP) is characterized by a diminished
platelet count, an autoimmune condition with antibodies against platelets and an
increased tendency to bleed. The association between ITP and solid tumors is
uncommon. Cytokine-induced killer (CIK) cell therapy is a well tolerated and
promising cancer treatment with minimal toxicity. For the first time, CIK cell
therapy was reported to be followed by ITP. The mechanism through which CIK
induces ITP remains unclear. Imbalanced ratio of Th cells, decreased numbers or
impaired function of Treg cells and excessive secretion of cytokines inducing
abnormal activation of B cells may be among the possible reasons. Therefore, a
better understanding of this rare condition will require further investigation of
these cases.
PMID- 27485075
TI - A pooled analysis of nivolumab for the treatment of advanced non-small-cell lung
cancer and the role of PD-L1 as a predictive biomarker.
AB - BACKGROUND: Recent studies with nivolumab (a monoclonal antibody against
programmed cell death 1 [PD-1] receptor) have shown promise non-small-cell lung
cancer (NSCLC) treatment. METHODS: To review available clinical trials data in
order to assess nivolumab efficacy and the role of tumoral PDL-1 expression as a
biomarker. RESULTS: Nine eligible studies included 2102 patients. In the second
line setting, nivolumab achieved a 1-year survival rate of 41%; and in the first
line, a 1-year survival rate of 76%. For those with PD-L1 expression <1%,
nivolumab showed a trend for improved survival compared with docetaxel.
CONCLUSIONS: The available data reinforce nivolumab activity against NSCLC in
first-line or subsequent lines. Although PD-L1 expression is related to greater
response, PD-L1 negative patients had also some benefit.
PMID- 27485076
TI - Use of LDH and autoimmune side effects to predict response to ipilimumab
treatment.
AB - BACKGROUND: Ipilimumab is a cytotoxic T-lymphocyte antigen-4 antibody that
enhances T-cell activity and proliferation. METHODS: In a retrospective analysis
of 86 patients the clinical benefits of ipilimumab treatment were correlated with
laboratory and clinical data. RESULTS: A lactate dehydrogenase (LDH) value within
the normal range before the start of therapy was significantly correlated with
better OS (p <= 0.009). An increase in LDH level after two cycles was indicative
of a poor outcome, and was significantly negatively correlated with treatment
response and overall survival and progression-free survival. 42% of all patients
suffered from autoimmune toxicity (CTCAE grades 2-4). The occurrence of
autoimmune toxicity clearly correlated with clinical benefit. CONCLUSION: Changes
in LDH level and side effects correlate with response to therapy and survival.
PMID- 27485077
TI - A recombinant TGF-beta1 vaccine ameliorates diabetic nephropathy in OLETF rats.
AB - AIM: The aim of this study was to investigate the potential of a recombinant
vaccine encoding TGF-beta1 in OLETF rats with diabetic nephropathy (DN). METHODS:
OLETF rats were treated with vehicle or TGF-beta1 vaccine. LETO rats were used as
normal controls. At 42 weeks after immunization with vaccine, samples from blood,
urine and kidney were collected for biochemical, histologic, immunohistochemical
and molecular analyses. RESULTS: OLETF rats treated with the vaccine reduced
blood glucose levels, improved renal pathological changes, and inhibited
overexpression of TGF-beta1 and p-Smad3, as well as MCP-1, TNF-alpha and IL
1beta. CONCLUSION: TGF-beta1 vaccine attenuated diabetic nephropathy in OLETF
rats through reduction of inflammation, improvement of kidney fibrosis and
partial correction of glucose metabolism.
PMID- 27485078
TI - Tumor-derived vaccines containing CD200 inhibit immune activation: implications
for immunotherapy.
AB - There are over 400 ongoing clinical trials using tumor-derived vaccines. This
approach is especially attractive for many types of brain tumors, including
glioblastoma, yet so far the clinical response is highly variable. One
contributor to poor response is CD200, which acts as a checkpoint blockade,
inducing immune tolerance. We demonstrate that, in response to vaccination,
glioma-derived CD200 suppresses the anti-tumor immune response. In contrast, a
CD200 peptide inhibitor that activates antigen-presenting cells overcomes immune
tolerance. The addition of the CD200 inhibitor significantly increased leukocyte
infiltration into the vaccine site, cytokine and chemokine production, and
cytolytic activity. Our data therefore suggest that CD200 suppresses the immune
system's response to vaccines, and that blocking CD200 could improve the efficacy
of cancer immunotherapy.
PMID- 27485079
TI - Current status of engineered T-cell therapy for synovial sarcoma.
AB - Synovial sarcoma is a rare soft tissue sarcoma characterized by a t(X;18)
translocation, which results in a SYT-SSX gene fusion. In the metastatic setting,
chemotherapy has limited, durable efficacy prompting the necessity for new
therapeutic modalities. One emerging new strategy involves T-cell-directed
therapy such as tumor-infiltrating lymphocytes or the development of T cells that
are genetically engineered to express a T-cell receptor against a cancer testis
antigen. Of these approaches, engineered T cells that recognize NY-ESO-1 are the
furthest along in development. Completed and on-going clinical trials have shown
promise and there are efforts to continue to optimize the current approach.
PMID- 27485080
TI - PD-L1 expression and outcome of advanced melanoma patients treated with anti-PD
1/PD-L1 agents: a meta-analysis.
AB - AIM: This meta-analysis aims at assessing the correlation of PD-L1 levels and
response PD-1/PD-L1 inhibitors in advanced malignant melanoma. METHODS: Eligible
studies included those evaluating PD-1/PD-L1 inhibitors in advanced melanoma and
correlating the outcomes to PD-L1 levels. RESULTS: After preclusion of ineligible
studies, 11 studies were included. For PD-L1 >1% patients versus PD-L1 <1%
patients treated with PD-1/PD-L1 targeted agents, the OR of ORR was 2.81 (95% CI:
1.64-4.82; p = 0.0002); while for PD-L1 >5% patients versus PD-L1 <5% patients,
it was 2.22 (95% CI: 1.71-2.87; p < 0.00001). CONCLUSION: The current analysis
indicates the value of PD-L1 positivity in predicting higher response from PD
1/PD-L1 agents. This molecular predictor - together with other predictors - may
help further individualize treatment options for metastatic melanoma patients.
PMID- 27485081
TI - Perspectives of ofatumumab as CD20 targeted therapy in rheumatoid arthritis and
other autoimmune diseases.
AB - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition viewed
as a severe destructive disease. The treatment strategies include anti-CD20
monoclonal antibody (mAb)-targeting B cells. Ofatumumab specifically targets a
membrane-proximal epitope on the CD20 molecule distinct from other anti-CD20
antibodies including rituximab and ocrelizumab, and bind the epitope located on
the large loop of CD20. This explains a more durable B-cell depletion and a
different pharmacodynamic. We review the pharmacodynamic of B-cell depletion and
analyze the results in RA and other B-cell-mediated autoimmune diseases. The
randomized trial in RA showed clinical efficacy comparable to rituximab at week
24. However, structural impact has not been demonstrated. Studies including RA
patients refractory to rituximab would be useful to define the optimal strategy
of ofatumumab therapy.
PMID- 27485083
TI - Tau-based therapeutics for Alzheimer's disease: active and passive immunotherapy.
AB - Pharmacological manipulation of tau protein in Alzheimer's disease included
microtubule-stabilizing agents, tau protein kinase inhibitors, tau aggregation
inhibitors, active and passive immunotherapies and, more recently, inhibitors of
tau acetylation. Animal studies have shown that both active and passive
approaches can remove tau pathology and, in some cases, improve cognitive
function. Two active vaccines targeting either nonphosphorylated (AAD-vac1) and
phosphorylated tau (ACI-35) have entered Phase I testing. Notwithstanding, the
recent discontinuation of the monoclonal antibody RG7345 for Alzheimer's disease,
two other antitau antibodies, BMS-986168 and C2N-8E12, are also currently in
Phase I testing for progressive supranuclear palsy. After the recent impressive
results in animal studies obtained by salsalate, the dimer of salicylic acid,
inhibitors of tau acetylation are being actively pursued.
PMID- 27485084
TI - Strategies to control human cytomegalovirus infection in adult hematopoietic stem
cell transplant recipients.
AB - Human cytomegalovirus (HCMV) represents the major viral complication after
hematopoietic stem cell transplantation. HCMV infection may be controlled by the
reconstituting immune system and remain subclinical or can lead to severe
systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune
reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV
disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre
emptive therapy strategies guided by virological monitoring dramatically reduced
the occurrence of HCMV disease. However, late-onset end-organ disease may occur
in some patients with apparent immune reconstitution. In the near future,
introduction of immunological monitoring and immunotherapies could markedly
improve management of HCMV infection.
PMID- 27485085
TI - Erratum.
PMID- 27485082
TI - Anti-GD2 mAbs and next-generation mAb-based agents for cancer therapy.
AB - Tumor-specific monoclonal antibodies (mAbs) have demonstrated efficacy in the
clinic, becoming an important approach for cancer immunotherapy. Due to its
limited expression on normal tissue, the GD2 disialogangloside expressed on
neuroblastoma cells is an excellent candidate for mAb therapy. In 2015,
dinutuximab (an anti-GD2 mAb) was approved by the US FDA and is currently used in
a combination immunotherapeutic regimen for the treatment of children with high
risk neuroblastoma. Here, we review the extensive preclinical and clinical
development of anti-GD2 mAbs and the different mechanisms by which they mediate
tumor cell killing. In addition, we discuss different mAb-based strategies that
capitalize on the targeting ability of anti-GD2 mAbs to potentially deliver, as
monotherapy, or in combination with other treatments, improved antitumor
efficacy.
PMID- 27485086
TI - Evaluation of Giardia lamblia thioredoxin reductase as drug activating enzyme and
as drug target.
AB - The antioxidative enzyme thioredoxin reductase (TrxR) has been suggested to be a
drug target in several pathogens, including the protist parasite Giardia lamblia.
TrxR is also believed to catalyse the reduction of nitro drugs, e.g.
metronidazole and furazolidone, a reaction required to render these compounds
toxic to G. lamblia and other microaerophiles/anaerobes. It was the objective of
this study to assess the potential of TrxR as a drug target in G. lamblia and to
find direct evidence for the role of this enzyme in the activation of
metronidazole and other nitro drugs. TrxR was overexpressed approximately 10-fold
in G. lamblia WB C6 cells by placing the trxR gene behind the arginine deiminase
(ADI) promoter on a plasmid. Likewise, a mutant TrxR with a defective disulphide
reductase catalytic site was strongly expressed in another G. lamblia WB C6 cell
line. Susceptibilities to five antigiardial drugs, i.e. metronidazole,
furazolidone, nitazoxanide, albendazole and auranofin were determined in both
transfectant cell lines and compared to wildtype. Further, the impact of all five
drugs on TrxR activity in vivo was measured. Overexpression of TrxR rendered G.
lamblia WB C6 more susceptible to metronidazole and furazolidone but not to
nitazoxanide, albendazole, and auranofin. Of all five drugs tested, only
auranofin had an appreciably negative effect on TrxR activity in vivo, albeit to
a much smaller extent than expected. Overexpression of TrxR and mutant TrxR had
hardly any impact on growth of G. lamblia WB C6, although the enzyme also exerts
a strong NADPH oxidase activity which is a source of oxidative stress. Our
results constitute first direct evidence for the notion that TrxR is an activator
of metronidazole and furazolidone but rather question that it is a relevant drug
target of presently used antigiardial drugs.
PMID- 27485087
TI - High-throughput in vitro assay to evaluate the cytotoxicity of liberated platinum
compounds for stimulating neural electrodes.
AB - BACKGROUND: It is currently unclear how the platinum (Pt) species released from
platinum-containing stimulating electrodes may affect the health of the
surrounding tissue. This study develops an effective system to assess the
cytotoxicity of any electrode-liberated Pt over a short duration, to screen
systems before future in vivo testing. NEW METHOD: A platinum electrode was
stimulated for two hours under physiologically relevant conditions to induce the
liberation of Pt species. The total concentration of liberated Pt species was
quantified and the concentration found was used to develop a range of Pt species
for our model system comprised of microglia and neuron-like cells. RESULTS: Under
our stimulation conditions (k=2.3, charge density of 57.7MUC/cm2), Pt was
liberated to a concentration of 1ppm. Interestingly, after 24h of Pt exposure,
the dose-dependent cytotoxicity plots revealed that cell death became
statistically significant at 10ppm for microglia and 20ppm for neuronal cells.
However, in neuron-like cell cultures, concentrations above 1ppm resulted in
significant neurite loss after 24h. COMPARISON WITH EXISTING METHODS: To our
knowledge, there does not exist a simple, in vitro assay system for assessing the
cytotoxicity of Pt liberated from stimulating neural electrodes. CONCLUSIONS:
This work describes a simple model assay that is designed to be applicable to
almost any electrode and stimulation system where the electrode is directly
juxtaposed to the neural target. Based on the application, the duration of
stimulation and Pt exposure may be varied.
PMID- 27485088
TI - Excitation Light Dose Engineering to Reduce Photo-bleaching and Photo-toxicity.
AB - It is important to determine the most effective method of delivering light onto a
specimen for minimal light induced damage. Assays are presented to measure photo
bleaching of fluorophores and photo-toxicity to living cells under different
illumination conditions. Turning the light off during part of the experimental
time reduced photo-bleaching in a manner proportional to the time of light
exposure. The rate of photo-bleaching of EGFP was reduced by 9-fold with light
pulsing on the micro-second scale. Similarly, in living cells, rapid line
scanning resulted in reduced cell stress as measured by mitochondrial potential,
rapid cell protrusion and reduced cell retraction. This was achieved on a
commercial confocal laser scanning microscope, without any compromise in image
quality, by using rapid laser scan settings and line averaging. Therefore this
technique can be implemented broadly without any software or hardware upgrades.
Researchers can use the rapid line scanning option to immediately improve image
quality on fixed samples, reduce photo-bleaching for large high resolution 3D
datasets and improve cell health in live cell experiments. The assays developed
here can be applied to other microscopy platforms to measure and optimize light
delivery for minimal sample damage and photo-toxicity.
PMID- 27485089
TI - Differing Philosophical Approaches to Treating Patients.
PMID- 27485090
TI - Availability and Readability of Online Patient Education Materials Regarding
Regional Anesthesia Techniques for Perioperative Pain Management.
AB - Objective: Patient education materials (PEM) should be written at a sixth-grade
reading level or lower. We evaluated the availability and readability of online
PEM related to regional anesthesia and compared the readability and content of
online PEM produced by fellowship and nonfellowship institutions. Methods: With
IRB exemption, we constructed a cohort of online regional anesthesia PEM by
searching Websites from North American academic medical centers supporting a
regional anesthesiology and acute pain medicine fellowships and used a
standardized Internet search engine protocol to identify additional nonfellowship
Websites with regional anesthesia PEM based on relevant keywords. Readability
metrics were calculated from PEM using the TextStat 0.1.4 textual analysis
package for Python 2.7 and compared between institutions with and without a
fellowship program. The presence of specific descriptive PEM elements related to
regional anesthesia was also compared between groups. Results: PEM from 17
fellowship and 15 nonfellowship institutions were included in analyses. The mean
(SD) Flesch-Kincaid Grade Level for PEM from the fellowship group was 13.8 (2.9)
vs 10.8 (2.0) for the nonfellowship group (p = 0.002). We observed no other
differences in readability metrics between fellowship and nonfellowship
institutions. Fellowship-based PEM less commonly included descriptions of the
following risks: local anesthetic systemic toxicity (p = 0.033) and injury due to
an insensate extremity (p = 0.003). Conclusions: Available online PEM related to
regional anesthesia are well above the recommended reading level. Further,
fellowship-based PEM posted are at a higher reading level than PEM posted by
nonfellowship institutions and are more likely to omit certain risk descriptions.
PMID- 27485091
TI - Rationalising pKa shifts in Bacillus circulans xylanase with computational
studies.
AB - Bacillus circulans xylanase (BcX), a family 11 glycoside hydrolase, catalyses the
hydrolysis of xylose polymers with a net retention of stereochemistry. Glu172 in
BcX is believed to act as a general acid by protonating the aglycone during
glycosylation, and then as a general base to facilitate the deglycosylation step.
The key to the dual role of this general acid/base lies in its protonation
states, which depend on its intrinsic pKa value and the specific environment
which it resides within. To fully understand the detailed molecular features in
BcX to establish the dual role of Glu172, we present a combined study based on
both atomistic simulations and empirical models to calculate pKa shifts for the
general acid/base Glu172 in BcX at different functional states. Its pKa values
and those of nearby residues, obtained based on QM/MM free energy calculations,
MCCE and PROPKA, show a good agreement with available experimental data.
Additionally, our study provides additional insights into the effects of
structural and electrostatic perturbations caused by mutations and chemical
modifications, suggesting that the local solvation environment and mutagenesis of
the residues adjacent to Glu172 establish its dual role during hydrolysis. The
strengths and limitations of various methods for calculating pKas and pKa shifts
have also been discussed.
PMID- 27485092
TI - The Rainbow Scale for Assessing Breast Ptosis: Validation of Three Different
Views.
AB - BACKGROUND: Photographic scales have become an increasingly used tool in
objectively assessing outcomes in aesthetic surgery. However, no online
photographic scale for assessing breast ptosis has been developed yet that is
readily available. OBJECTIVES: This study was designed to validate the online
Rainbow Scale for the assessment of breast ptosis for the anterior-posterior
(AP), lateral, and oblique views. METHODS: For the five grades of the Rainbow
Scale format, standardized reference photographs were selected. Six plastic
surgeons rated 15 photographs for each view three times. Intra- and inter
observer agreements were calculated by using the weighted kappa coefficient and
differences in intra- and inter-observer agreements between the three views were
assessed for statistical significance using the Kruskal-Wallis test. RESULTS: The
mean intra-observer agreements were 0.91 (range, 0.82-0.98) for the AP view, 0.88
(range, 0.77-1.00) for the oblique view, and 0.86 (range, 0.74-0.97) for the
lateral view and did not vary significantly between all three views. The mean
inter-observer agreements were 0.88 (range, 0.77-0.95) for the AP view, 0.84
(range, 0.72-0.94) for the oblique view, and 0.82 (range, 0.58-0.95) for the
lateral view. The mean inter-observer agreements of the AP view varied
significantly from the oblique view (P = .012) and the lateral view (P = .001).
CONCLUSIONS: The Rainbow Scale for breast ptosis has been validated for the AP
view, the lateral view, and the oblique view and is reproducible and reliable for
the assessment of breast ptosis in three different views in an online setup.
LEVEL OF EVIDENCE: 4 Diagnostic.
PMID- 27485093
TI - Metabolic demand of the hepatic cell cycle.
PMID- 27485094
TI - Repair of segmental radial defects in dogs using tailor-made titanium mesh cages
with plates combined with calcium phosphate granules and basic fibroblast growth
factor-binding ion complex gel.
AB - Repair of large segmental defects of long bones are a tremendous challenge that
calls for a novel approach to supporting immediate weight bearing and bone
regeneration. This study investigated the functional and biological
characteristics of a combination of a tailor-made titanium mesh cage with a plate
(tTMCP) with tetrapod-shaped alpha tricalcium phosphate granules (TB) and basic
fibroblast growth factor (bFGF)-binding ion complex gel (f-IC gel) to repair 20
mm segmental radial defects in dogs. The defects were created surgically in 18
adult beagle dogs and treated by implantation of tTMCPs with TB with (TB-gel
group) or without (TB group) f-IC gel. Each tTMCP fitted the defect well, and all
dogs could bear weight on the affected limb immediately after surgery. Dogs were
euthanized 4, 8 and 24 weeks after implantation. Histomorphometry showed greater
infiltration of new vessels and higher bone union rate in the TB-gel group than
in the TB group. The lamellar bone volume and mineral apposition rate did not
differ significantly between the groups, indicating that neovascularization may
be the primary effect of f-IC gel on bone regeneration. This combination method
which is tTMCP combined with TB and f-IC gel, would be useful for the treatment
of segmental long bone defects.
PMID- 27485095
TI - Cadmium Isotope Fractionation in Soil-Wheat Systems.
AB - Analyses of stable metal isotope ratios constitute a novel tool in order to
improve our understanding of biogeochemical processes in soil-plant systems. In
this study, we used such measurements to assess Cd uptake and transport in wheat
grown on three agricultural soils under controlled conditions. Isotope ratios of
Cd were determined in the bulk C and A horizons, in the Ca(NO3)2-extractable Cd
soil pool, and in roots, straw, and grains. The Ca(NO3)2-extractable Cd was
isotopically heavier than the Cd in the bulk A horizon (Delta(114/110)Cdextract
Ahorizon = 0.16 to 0.450/00). The wheat plants were slightly enriched in light
isotopes relative to the Ca(NO3)2-extractable Cd or showed no significant
difference (Delta(114/110)Cdwheat-extract = -0.21 to 0.030/00). Among the plant
parts, Cd isotopes were markedly fractionated: straw was isotopically heavier
than roots (Delta(114/110)Cdstraw-root = 0.21 to 0.410/00), and grains were
heavier than straw (Delta(114/110)Cdgrain-straw = 0.10 to 0.510/00). We suggest
that the enrichment of heavy isotopes in the wheat grains was caused by
mechanisms avoiding the accumulation of Cd in grains, such as the chelation of
light Cd isotopes by thiol-containing peptides in roots and straw. These results
demonstrate that Cd isotopes are significantly and systematically fractionated in
soil-wheat systems, and the fractionation patterns provide information on the
biogeochemical processes in these systems.
PMID- 27485096
TI - Cranium asymmetry in a modern Greek population sample of known age and sex.
AB - The aim of this paper is to evaluate and quantify cranium asymmetry, sexual
differences in the set of individual asymmetry scores, and the relationship
between fluctuating asymmetry and age, in a modern Greek population sample. In
addition, we test for the developmental origins of health and disease hypothesis
by assessing the correlation between fluctuating asymmetry and cause of death.
The study sample consisted of 173 crania of known sex and adult age (92 males, 81
females) belonging to individuals who lived in Greece during the twentieth
century. The three-dimensional coordinates of 77 ectocranial landmarks were
digitized using a Microscribe 3DX contact digitizer and landmark configurations
were analyzed using the generalized least-squares Procrustes method. Regarding
directional asymmetry, the results show that the human skull has a tendency for a
left-side excess for the Greek population. No significant directional asymmetry
differences between the sexes are found. The highest levels of fluctuating
asymmetry for both sexes are located on the skull base. The levels of fluctuating
asymmetry in all cranial regions appear higher for males than females.
Nevertheless, these differences do not present any statistical significance
between sexes. Additionally, there is no relationship between fluctuating
asymmetry scores and age for both males and females. Finally, the results of this
study could not confirm that early development has a significant impact on adult
health outcomes.
PMID- 27485097
TI - Study of genetic markers of CODIS and ESS systems in a population of individuals
from Cabo Verde living in Lisboa.
AB - Twenty-two autosomal short tandem repeats included in the PowerPlex(r) Fusion
System Amplification kit (Promega Corporation) were genotyped in a population
sample of 500 unrelated individuals from Cabo Verde living in Lisboa. Allelic
frequency data and forensic and statistical parameters were calculated and
evaluated in this work. The genetic relationship among immigrant population from
Cabo Verde living in Lisboa and other populations, such as Brazilian and Angola
immigrants living in Lisboa; Afro-Americans, Caucasians, Hispanics and Asians
living in the USA and the population from Lisboa was assessed, and a
multidimensional scaling plot was drown to show these results.
PMID- 27485098
TI - Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies,
including brain tumours.
AB - Hyperbaric oxygen (HBO) therapy is widely used as an adjunctive treatment for
various pathological states, predominantly related to hypoxic and/or ischaemic
conditions. It also holds promise as an approach to overcoming the problem of
oxygen deficiency in the poorly oxygenated regions of the neoplastic tissue.
Occurrence of local hypoxia within the central areas of solid tumours is one of
the major issues contributing to ineffective medical treatment. However, in anti
cancer therapy, HBO alone gives a limited curative effect and is typically not
applied by itself. More often, HBO is used as an adjuvant treatment along with
other therapeutic modalities, such as radio- and chemotherapy. This review
outlines the existing data regarding the medical use of HBO in cancer treatment,
with a particular focus on the use of HBO in the treatment of brain tumours. We
conclude that the administration of HBO can provide many clinical benefits in the
treatment of tumours, including management of highly malignant gliomas. Applied
immediately before irradiation, it is safe and well tolerated by patients,
causing rare and limited side effects. The results obtained with a combination of
HBO/radiotherapy protocol proved to be especially favourable compared to
radiation treatment alone. HBO can also increase the cytostatic effect of certain
drugs, which may render standard chemotherapy more effective. The currently
available data support the legitimacy of conducting further research on the use
of HBO in the treatment of malignancies.
PMID- 27485099
TI - Parenting Strategies to Deal with Children's Anxiety: Do Parents Do What They Say
They Do?
AB - Parents' perceptions about their strategies to deal with children's anxiety have
been minimally explored. Based on a mixed-method approach, the current study
compared the strategies that parents said they use more frequently to deal with
their child's anxious behaviors and the strategies they actually used during two
mildly anxiogenic interactions with their child. Forty-two parents of children
with anxiety disorders, aged 9-12 years, participated in the study. Semi
structured interviews were administered to identify parental perceptions about
their strategies to deal with their children's anxiety. Subsequently dyadic
interactions were observed and coded by two independent coders. We found
discrepancies relating to four strategies. Significantly more parents used
strategies based on overinvolvement and anxious behavior during the interactions
than had been reported by them in the interviews. In contrast, reassurance and
reinforcement of avoidance/dependence were used in interactions by fewer parents
than would be expected, according to the interviews. Relevant implications for
assessment and intervention with families of anxious children are suggested.
PMID- 27485100
TI - Augmenting Cognitive Behavior Therapy for School Refusal with Fluoxetine: A
Randomized Controlled Trial.
AB - This study investigates whether the augmentation of cognitive behavior therapy
(CBT) with fluoxetine improves outcomes in anxious school refusing adolescents
(11-16.5 years). Sixty-two participants were randomly allocated to CBT alone, CBT
+ fluoxetine or CBT + placebo. All treatments were well tolerated; with one
suicide-attempt in the CBT + placebo group. All groups improved significantly on
primary (school attendance) and secondary outcome measures (anxiety, depression,
self-efficacy and clinician-rated global functioning); with gains largely
maintained at 6-months and 1-year. Few participants were anxiety disorder free
after acute treatment. During the follow-up period anxiety and depressive
disorders continued to decline whilst school attendance remained stable, at
around 54 %. The only significant between-group difference was greater adolescent
reported treatment satisfaction in the CBT + fluoxetine group than the CBT alone
group. These results indicate the chronicity of school refusal, and the need for
future research into how to best improve school attendance rates.
PMID- 27485102
TI - Editorial.
PMID- 27485101
TI - MicroRNA-26a protects against cardiac hypertrophy via inhibiting GATA4 in rat
model and cultured cardiomyocytes.
AB - Pathological cardiac hypertrophy is characterized by deleterious changes
developed in cardiovascular diseases, whereas microRNAs (miRNAs) are involved in
the mediation of cardiac hypertrophy. To investigate the role of microRNA-26a
(miR-26a) in regulating cardiac hypertrophy and its functioning mechanisms,
overexpression and suppression of miR-26a via its mimic and inhibitor in a
transverse abdominal aortic constriction (TAAC)-induced rat model and in
angiotensin II (Ang II)-induced cardiomyocytes (CMs) was performed. In the rat
model, the heart weight (HW) compared with the body weight (BW), the CM area, and
expression of the hypertrophy-associated factors, atrial natriuretic factor (ANF)
and beta-myosin heavy chain (beta-MHC), were assessed. In CMs, the protein
synthesis rate was determined using a leucine incorporation assay. Mutation of
the GATA-binding protein 4 (GATA4) 3'-untranslated region (UTR) and
overexpression of GATA4 were performed to confirm whether GATA4 is the target of
miR-26a. The results indicated that miR-26a was significantly downregulated in
the heart tissue of the rat model, as well as in Ang II-induced CMs (P<0.05). The
TAAC-induced rat model exhibited a higher HW/BW ratio, a larger CM area, and
higher expression levels of ANF and beta-MHC. CMs, upon Ang II treatment, also
demonstrated a larger CM area, higher levels of ANF and beta-MHC, as well as
accelerated protein synthesis. miR-26a was not able to regulate GATA4 with
mutations in the 3'-UTR, indicating that GATA4 was the direct target of miR-26a.
Overexpression of GATA4 abrogated the inhibitory functions of miR-26a in cardiac
hypertrophy. Taken together, the present study suggested an anti-hypertrophic
role of miR-26a in cardiac hypertrophy, possibly via inhibition of GATA4. These
findings may be useful in terms of facilitating cardiac treatment, with potential
therapeutic targets and strategies.
PMID- 27485103
TI - Aspartate kinase involved in 4-hydroxy-3-nitrosobenzamide biosynthesis in
Streptomyces murayamaensis.
AB - Streptomyces murayamensis carries two aspartate kinase (AK) genes: one for the
biosynthesis of lysine, threonine, and methionine, and the other (nspJ) contained
in the biosynthetic gene cluster for the secondary metabolite, 4-hydroxy-3
nitrosobenzamide, for catalyzing the first reaction. AKs involved in the
biosynthesis of amino acids are often regulated allosterically by the end
products. In the present study, we characterized NspJ to investigate whether AKs
involved in secondary metabolism were also allosterically regulated. NspJ was in
alpha2beta2 and (alpha2beta2)2 heterooligomeric forms, and was insensitive to all
the compounds tested including lysine, threonine, and methionine. The reduction
in the activity following the removal of ammonium sulfate, which induced subunit
dissociation, suggests that the beta subunit may be involved in stabilizing the
structure of the alpha subunit in order to exhibit its activity. This study has
provided the first example of a feedback-insensitive alpha2beta2-type AK, which
is involved in the secondary metabolism.
PMID- 27485104
TI - Two-Tension-Band Technique in Revision Surgery for Fixation Failure of Patellar
Fractures.
AB - BACKGROUND Failed patellar fracture fixation is rare, and is usually attributed
to technical errors. There are no specific details available on how to address
this problem. We present our two-tension-band technique for fixing patellar
fractures. MATERIAL AND METHODS Between March 2010 and March 2013, 4 men and 2
women with failed fixation patellar fractures were treated in our department.
Their average age was 34 years (range 23-49 years). The initial fracture type was
C1 in 3, C2 in 1, and C3 in 2, according to the AO classification. The initial
fracture patterns included 3 transverse and 3 comminuted fractures. There were no
open fractures. All patients underwent internal fixation with a modified anterior
tension band (MATB) supplemented with cerclage wiring. All failures were caused
by tension bands sliding past the tip of the Kirschner wires. The mean time
between the primary and revision operations was 16.2 months (range 2-63 months).
We revised the fractures by two-separate-tension-band technique. RESULTS The mean
follow-up was 52 months (range 31-67 months). All patients healed
radiographically without complications at an average of 14.7 weeks (range 8-20
weeks). The Bostman knee score was excellent in 3 and good in 3. All patients
regained full extension and the mean range of flexion was 147.5 degrees (135-155
degrees ). CONCLUSIONS Use of this two-tension-band technique can avoid technical
errors and provide more secure fixation. We recommend it for both primary and
revision surgery of patellar fractures.
PMID- 27485105
TI - Effects of HeartWare ventricular assist device on the von Willebrand factor:
results of an academic Belgian center.
AB - BACKGROUND: Left Ventricular Assist Device (LVAD) is a promising therapy for
patients with advanced heart failure (HF), but bleeding complications remain an
important issue. Previous series show that acquired von Willebrand syndrome was
present in up to 100 % of first generation LVAD recipients. We report the effects
of new generation LVADs on vW factor (vWF) metabolism and activity in our center.
METHODS: Fifteen LVAD recipients (HeartWare(r), Framingham, MA, USA) were
compared to 12 HF patients, matched for age and body mass index. vWF antigen and
activity, as well as D-dimers, were measured on hemostasis analyzers. A vWF LVAD
induced alteration was evocated when the [vWF activity]/[vWF antigen] ratio was
<0.6. ADAMTS13 and high molecular weight multimers of vWF were also assessed.
RESULTS: LVAD recipients had similar levels of endothelial vWF production than
the HF subjects (137 +/- 14.5 vs. 147 +/- 11.7 %; respectively, p = 0.611) but a
decreased vWF activity (90 +/- 11 vs. 132.6 +/- 13 %; respectively, p = 0.017).
[vWF activity]/[vWF antigen] ratio was 0.65 +/- 0.02 in the LVAD recipients and
0.92 +/- 0.06 in the subjects with HF (p = 0.001). ADAMTS13 activity was 80.3 +/-
4.7 % in LVAD recipients and 96.2 +/- 3.5 % in the HF patients (p = 0.016). LVAD
patients disclosed markedly elevated D-dimers (3217.7 +/- 735 vs. 680.6 +/- 223.2
ng/mL FEU in the HF patients, p = 0.006). The LVAD patients experienced one major
hemorrhagic event and one systemic thrombotic event during the median follow-up
of 345 days. CONCLUSIONS: LVAD recipients achieved a new hemostatic equilibrium
characterized by infrequent major hemorrhagic and thrombotic events, despite a
mildly impaired vWF function and a markedly enhanced thrombin formation. TRIAL
REGISTRATION: ISRCTN39517567.
PMID- 27485107
TI - Use of a Simulated Model to Teach Male Adult Circumcision in Sub-Saharan Africa.
AB - Male adult circumcision (MC) has been shown to reduce the risk of HIV
transmission in men by 50-60 %. An upscaling in the training of providers to
perform circumcision is necessary to meet demand since MC is a key component of
essential surgery in the context of universal health coverage. We piloted a low
cost, high-fidelity model for training adult circumcision. Multi-centre,
multinational data were collected on 74 trainees and clinicians (trainers) in sub
Saharan Africa. Both trainers and trainees gave excellent feedback for the model
(content and face validity). The simulated model enables a safe and realistic
simulation experience to perform MC. The model is quick to set up and easily
transportable to multiple teaching sites.
PMID- 27485108
TI - A new xyelotomid (Hymenoptera) from the Middle Jurassic of China displaying
enigmatic venational asymmetry.
AB - BACKGROUND: Pterygota insects typically have symmetric veins in left and right
wings. For studying taxonomy and phylogeny of fossil insects, venational patterns
are commonly used as diagnostic characters, in conjunction with preserved body
characters. Some examples of asymmetrical venation are known among extant
insects, but only a few fossil insects with asymmetric wings have been reported,
among which a previously described xyelotomid of Hymenoptera, Xyelocerus
diaphanous, displays an unusual, small cell of vein Rs in the left forewing, but
not in the right. RESULTS: Herein we report a new sawfly of the family
Xyelotomidae, Aethotoma aninomorpha gen. et sp. nov., from the late Middle
Jurassic of China having a simple Sc in the forewing and Sc with two branches in
the hind wing. In additional, the new specimen exhibits an enigmatic venational
asymmetry. In the right forewing, crossvein 2r-rs of forms a loop, then forks
into 2 long branches reaching Rs, while 2r-rs of the left forewing forks into 2
short branches reaching Rs, in contrast to a linear 2r-rs in typical fossil and
extant sawflies. CONCLUSION: Such rare asymmetrical venation found from fossil
sawflies provides a glance at early occurrences of venational variability and
instability, or possibly aberrational development, for insects in the late Middle
Jurassic.
PMID- 27485106
TI - Robot-aided assessment of lower extremity functions: a review.
AB - The assessment of sensorimotor functions is extremely important to understand the
health status of a patient and its change over time. Assessments are necessary to
plan and adjust the therapy in order to maximize the chances of individual
recovery. Nowadays, however, assessments are seldom used in clinical practice due
to administrative constraints or to inadequate validity, reliability and
responsiveness. In clinical trials, more sensitive and reliable measurement
scales could unmask changes in physiological variables that would not be visible
with existing clinical scores.In the last decades robotic devices have become
available for neurorehabilitation training in clinical centers. Besides training,
robotic devices can overcome some of the limitations in traditional clinical
assessments by providing more objective, sensitive, reliable and time-efficient
measurements. However, it is necessary to understand the clinical needs to be
able to develop novel robot-aided assessment methods that can be integrated in
clinical practice.This paper aims at providing researchers and developers in the
field of robotic neurorehabilitation with a comprehensive review of assessment
methods for the lower extremities. Among the ICF domains, we included those
related to lower extremities sensorimotor functions and walking; for each chapter
we present and discuss existing assessments used in routine clinical practice and
contrast those to state-of-the-art instrumented and robot-aided technologies.
Based on the shortcomings of current assessments, on the identified clinical
needs and on the opportunities offered by robotic devices, we propose future
directions for research in rehabilitation robotics. The review and
recommendations provided in this paper aim to guide the design of the next
generation of robot-aided functional assessments, their validation and their
translation to clinical practice.
PMID- 27485109
TI - In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor
therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive
detection of emerging drug-resistant mutants.
AB - BACKGROUND: Imatinib-resistant chronic myeloid leukemia (CML) patients receiving
second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib
have a higher risk of disease relapse and progression and not infrequently BCR
ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this
setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater
chances of efficacy for subsequent salvage therapy and limit the biological
consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already
set up and validated next-generation deep amplicon sequencing (DS) assay, we
aimed to assess whether DS may allow a larger window of detection of emerging BCR
ABL1 KD mutants predicting for an impending relapse. METHODS: a total of 125
longitudinal samples from 51 CML patients who had acquired dasatinib- or
nilotinib-resistant mutations during second-line therapy were analyzed by DS from
the time of failure and mutation detection by conventional sequencing backwards.
BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had
'optimal response', 'warning' or 'failure' at the time of first mutation
detection by DS. RESULTS: DS was able to backtrack dasatinib- or nilotinib
resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median
mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5
%); median interval between detection by DS and detection by conventional
sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were
detectable at baseline. In the remaining cases, response level at the time
mutations were first detected by DS could be defined as 'Warning' (according to
the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as
'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or
nilotinib-resistant mutations were detected by DS in 15 randomly selected
patients with 'warning' at various timepoints, that later turned into optimal
responders with no treatment changes. CONCLUSIONS: DS enables a larger window of
detection of emerging BCR-ABL1 KD mutations predicting for an impending relapse.
A 'Warning' response may represent a rational trigger, besides 'Failure', for DS
based mutation screening in CML patients undergoing second-line TKI therapy.
PMID- 27485110
TI - The comprehensive profile of fermentation products during in situ CO2 recycling
by Rubisco-based engineered Escherichia coli.
AB - BACKGROUND: In our previous study, the feasibility of Rubisco-based engineered E.
coli (that contains heterologous phosphoribulokinase (PrkA) and Rubisco) for in
situ CO2 recycling during the fermentation of pentoses or hexoses was
demonstrated. Nevertheless, it is perplexing to see that only roughly 70 % of the
carbon fed to the bacterial culture could be accounted for in the standard
metabolic products. This low carbon recovery during fermentation occurred even
though CO2 emission was effectively reduced by Rubisco-based engineered pathway.
RESULTS: In this study, the heterologous expression of form I Rubisco was found
to enhance the accumulation of pyruvate in Escherichia coli MZLF [E. coli
BL21(DE3) Deltazwf, Deltaldh, Deltafrd]. This may be attributed to the enhanced
glycolytic reaction supported by the increased biomass and the ethanol/acetate
ratio. Besides, it was found that the transcription of arcA (encodes the redox
dependent transcriptional activators ArcA that positively regulates the
transcription of pyruvate formate-lyase) was down-regulated in the presence of
Rubisco. The enhanced accumulation of pyruvate also occurs when PrkA is co
expressed with Rubisco in E. coli MZLF. Furthermore, E. coli containing Rubisco
based engineered pathway has a distinct profile of the fermentation products,
indicating CO2 was converted into fermentation products. By analyzing the ratio
of total C-2 (2-carbon fermentation products) to total C-1 (1-carbon fermentation
product) of MZLFB (MZLF containing Rubisco-based engineered pathway), it is
estimated that 9 % of carbon is directed into Rubisco-based engineered pathway.
CONCLUSIONS: Here, we report for the first time the complete profile of
fermentation products using E. coli MZLF and its derived strains. It has been
shown that the expression of Rubisco alone in MZLF enhances the accumulation of
pyruvate. By including the contribution of pyruvate accumulation, the perplexing
problem of low carbon recovery during fermentation by E. coli containing Rubisco
based engineered pathway has been solved. 9 % of glucose consumption is directed
from glycolysis to Rubisco-based engineered pathway in MZLFB. The principle
characteristics of mixotroph MZLFB are the high bacterial growth and the low CO2
emission.
PMID- 27485111
TI - A protocol for a systematic review of non-randomised evaluations of strategies to
improve participant recruitment to randomised controlled trials.
AB - BACKGROUND: Randomised controlled trials guard against selection bias and
therefore offer the fairest way of evaluating healthcare interventions such as
medicinal products, devices and services. Recruitment to trials can be extremely
difficult, and poor recruitment can lead to extensions to both time and budget
and may result in an underpowered study which does not satisfactorily answer the
original research question. In the worst cases, a trial may be abandoned, causing
huge waste. The evidence to support the choice of recruitment interventions is
currently weak. Non-randomised evaluations of recruitment interventions are
currently rejected on grounds of poor methodological quality, but systematic
evaluation and assessment of this substantial body of work (using Grading of
Recommendations Assessment, Development and Evaluation (GRADE) where possible)
may provide useful information to support and inform the recruitment decisions of
trialists and the research priorities of methodology researchers. METHODS: The
following databases will be searched for relevant studies: Cochrane Methodology
Register, MEDLINE, EMBASE, CINAHL and PsycINFO. Any non-randomised study that
includes a comparison of two or more interventions to improve recruitment to
randomised controlled trials will be included. We will not apply any restrictions
on publication date, language or journal. The primary outcome will be the number
of individuals or centres recruited into a randomised controlled trial. The
secondary outcome will be cost per recruit. Two reviewers will independently
screen abstracts for eligible studies, and then, full texts of potentially
relevant records will be reviewed. Disagreements will be resolved through
discussion. The methodological quality of studies will be assessed using the
Cochrane risk of bias tool for non-randomised studies, and the GRADE system will
be used if studies are pooled. DISCUSSION: This review aims to summarise the
evidence on methods used to improve recruitment to randomised controlled trials.
Carrying out a systematic review including only data from non-randomised studies
is a novel approach, and one which some may argue is futile. However, we believe
that the systematic evaluation of what is likely to be a substantial amount of
research activity is necessary, worthwhile, and will yield valuable results for
the clinical trials community regardless of whether the outcomes find in favour
of one or more interventions. Should the results of this review suggest that non
randomised evaluations do have something to offer trialists planning their
recruitment strategies, the review may be combined in the future with the
Cochrane review of randomised evaluations to produce a full review of recruitment
strategies encompassing both randomised and non-randomised evaluation methods.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037718.
PMID- 27485112
TI - Tescalcin expression contributes to invasive and metastatic activity in
colorectal cancer.
AB - We reported previously that tescalcin (TESC) levels were higher in tissue and
serum from colorectal cancer (CRC) patients and suggested that TESC was a
potential oncotarget in CRC. The aim of this study was to investigate the
function of TESC in CRC invasion and metastatic potential. TESC expression was
knocked down in CRC cells using small interfering RNA (siRNA). The expression of
TESC siRNA reduced cell migration and invasion by inhibiting matrix
metalloprotease (MMP) and the epithelial-mesenchymal transition (EMT) pathway. RT
PCR and Western blot analysis showed that TESC siRNA induced E-cadherin.
Consistently, TESC overexpression in HCT116 (HCT/TESC) cells enhanced cell
migration and invasion by activating MMP and the EMT pathway and reducing E
cadherin. The formation of liver metastatic nodules in vivo was strongly
increased in mice injected with HCT/TESC cells compared with that in mice
injected with HCT/mock cells. This study demonstrates that TESC is involved in
cell migration, invasion, and EMT during CRC tumor invasion. These results
implicate TESC as a metastatic mediator and provide a biological rationale for
the adverse prognosis associated with elevated TESC expression in human CRC.
PMID- 27485114
TI - Construction and application of a lung cancer stem cell model: antitumor drug
screening and molecular mechanism of the inhibitory effects of sanguinarine.
AB - Lung cancer is a neoplasm with a 5-year survival rate of less than 15 % and a
leading cause of death worldwide, despite recent progress in treatment and
diagnostic methods. Lung cancer stem-like cells (CSCs) are pivotal in lung cancer
metastasis and drug resistance. This study aimed to develop lung CSCs that stably
express stem cell properties through transfection to further screen traditional
Chinese herbal compounds. Lung adenocarcinoma stem cells, which include various
phenotypic subgroups, are normally characterized by high expression levels of
pluripotent stem cell genes, particularly Nanog and OCT4. Plasmids containing
Nanog and OCT4 were constructed and transfected into cells, and lung CSCs were
identified not only in vitro using RT-PCR, Western blotting, plate cloning,
sphere formation, drug resistance, and transwell migration but also in vivo using
a nude mouse tumorigenicity assay. Subsequently, sanguinarine, which is derived
from the whole leaves of the traditional Chinese medicine celandine, was
identified through the high-throughput screening of a small-molecule compound
library. Investigation of the molecular mechanisms of the effects of sanguinarine
revealed that it significantly inhibited lung CSC proliferation, invasion, and
apoptosis, possibly via downregulation of the Wnt/beta-catenin signaling pathway.
Our results indicate that lung CSCs established by gene transfection may provide
a stable and effective method of constructing CSCs to effectively screen
potential antitumor drugs. Furthermore, these results suggest that sanguinarine
may be a natural antitumor compound that targets lung CSCs, laying a foundation
for further clinical study.
PMID- 27485113
TI - Identification of novel biomarkers associated with poor patient outcomes in
invasive breast carcinoma.
AB - Breast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38
million new cases and 460,000 deaths worldwide annually. Despite the significant
advances in the identification of molecular markers and different modalities of
treatment for primary BC, the ability to predict its metastatic behavior is still
limited. The purpose of this study was to identify novel molecular markers
associated with distinct clinical outcomes in a Brazilian cohort of BC patients.
We generated global gene expression profiles using tumor samples from 24 patients
with invasive ductal BC who were followed for at least 5 years, including a group
of 15 patients with favorable outcomes and another with nine patients who
developed metastasis. We identified a set of 58 differentially expressed genes (p
<= 0.01) between the two groups. The prognostic value of this metastasis
signature was corroborated by its ability to stratify independent BC patient
datasets according to disease-free survival and overall survival. The
upregulation of B3GNT7, PPM1D, TNKS2, PHB, and GTSE1 in patients with poor
outcomes was confirmed by quantitative reverse transcription polymerase chain
reaction (RT-qPCR) in an independent sample of patients with BC (47 with good
outcomes and eight that presented metastasis). The expression of BCL2-associated
agonist of cell death (BAD) protein was determined in 1276 BC tissue samples by
immunohistochemistry and was consistent with the reduced BAD mRNA expression
levels in metastatic cases, as observed in the oligoarray data. These findings
point to novel prognostic markers that can distinguish breast carcinomas with
metastatic potential from those with favorable outcomes.
PMID- 27485115
TI - Clinical significance of beta2-adrenergic receptor expression in patients with
surgically resected gastric adenocarcinoma.
AB - The beta2-adrenergic receptor (beta2-AR) is highly expressed in various human
neoplasms and has been considered a novel therapeutic target of cancer treatment.
However, the clinicopathological significance of beta2-AR expression in patients
with gastric cancer (GC) remains unclear. The aim of this study was to explore
beta2-AR expression and its prognostic significance. A total of 331 patients with
surgically resected GC were evaluated. Tumor sections were stained
immunohistochemically for beta2-AR. And, we confirmed beta2-AR expression in the
GC cell lines by Western blot. beta2-AR was highly expressed in 30.5 % of GC
patients. Expression was significantly associated with age, T factor, tumor
differentiation, histology of non-signet cells, lymphatic permeation, and
vascular invasion. And, all the GC cell lines expressed beta2-AR. On univariate
analysis, age, disease stage, T factor, N factor, lymphatic permeation, vascular
invasion, and beta2-AR expression were significantly associated with overall
survival. Although the multivariate analysis did not indicate that beta2-AR
expression was independently prognostic of survival, high-level beta2-AR
expression was associated with significantly poorer survival of GC patients with
well or moderately differentiated tumors. beta2-AR expression was a significant
predictor of tumor aggressiveness in, and poorer survival of, patients with GC.
PMID- 27485116
TI - Tumor suppressor Fbxw7 antagonizes WNT signaling by targeting beta-catenin for
degradation in pancreatic cancer.
AB - Pancreatic cancer is one of the deadliest solid malignancies associated with
aberrant Wnt signaling activation. Fbxw7 mutations have been implicated in the
development of pancreatic cancer, whereas the exact mechanism of this ubiquitin
ligase as a tumor suppressor remains unclear in pancreatic carcinogenesis. Here,
we describe that Fbxw7 is downregulated upon pancreatic cancer development.
Depletion of Fbxw7 results in tumor suppression in pancreatic cancer cells, while
Fbxw7 overexpression inhibits pancreatic cancer cell proliferation and invasion.
Considering the negative correlation between Fbxw7 and beta-catenin, we find that
Fbxw7 antagonizes Wnt signaling through targeting beta-catenin for its
degradation. Moreover, the inhibitory effect of Fbxw7 on pancreatic cancer cell
proliferation is mainly executed by the destruction of the Wnt/beta-catenin
signaling pathway. We also reveal that c-myc, a widely accepted target of Fbxw7,
is also transcriptionally regulated by the Fbxw7/beta-catenin axis in pancreatic
cancer cells. Collectively, our results demonstrate that Fbxw7 is a novel
regulator of Wnt/beta-catenin signaling-dependent regulation of pancreatic cancer
cell growth and invasion, and inactivation of Fbxw7 in pancreatic cancer tissues
might be the reason for the aberrant activation of Wnt signaling.
PMID- 27485117
TI - Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the
fragile X mouse model.
AB - Astrocytes are key participants in various aspects of brain development and
function, many of which are executed via secreted proteins. Defects in astrocyte
signaling are implicated in neurodevelopmental disorders characterized by
abnormal neural circuitry such as Fragile X syndrome (FXS). In animal models of
FXS, the loss in expression of the Fragile X mental retardation 1 protein (FMRP)
from astrocytes is associated with delayed dendrite maturation and improper
synapse formation; however, the effect of astrocyte-derived factors on the
development of neurons is not known. Thrombospondin-1 (TSP-1) is an important
astrocyte-secreted protein that is involved in the regulation of spine
development and synaptogenesis. In this study, we found that cultured astrocytes
isolated from an Fmr1 knockout (Fmr1 KO) mouse model of FXS displayed a
significant decrease in TSP-1 protein expression compared to the wildtype (WT)
astrocytes. Correspondingly, Fmr1 KO hippocampal neurons exhibited morphological
deficits in dendritic spines and alterations in excitatory synapse formation
following long-term culture. All spine and synaptic abnormalities were prevented
in the presence of either astrocyte-conditioned media or a feeder layer derived
from FMRP-expressing astrocytes, or following the application of exogenous TSP-1.
Importantly, this work demonstrates the integral role of astrocyte-secreted
signals in the establishment of neuronal communication and identifies soluble TSP
1 as a potential therapeutic target for Fragile X syndrome.
PMID- 27485118
TI - A rare cardiopulmonary parasite of the European badger, Meles meles: first
description of the larvae, ultrastructure, pathological changes and molecular
identification of Angiostrongylus daskalovi Janchev & Genov 1988.
AB - BACKGROUND: Angiostrongylus daskalovi is a rare cardiopulmonary nematode
infecting badgers. The parasite was described in 1988 and, since then, found only
once in mustelids in Europe. The present study aims to report new cases of patent
A. daskalovi infection in badgers from northern Romania and to provide new
information on its ultrastructure, molecular diagnosis, and pathology. METHODS:
Eight road-killed or hunted badgers originating from Maramures and Alba counties
in Romania were collected and necropsied. Adults and larvae of cardio-pulmonary
nematodes were collected and examined by light and scanning electron microscopy
(SEM). Genomic DNA was extracted from adults and first-stage larvae (L1). PCR
amplification of the internal transcribed spacer 2 (ITS2, ~500 bp) of the rRNA
gene was performed. Amplicons were purified, sequenced, and compared to those
available in the GenBank database. Histopathological examination of the lungs was
performed and lesions described. RESULTS: The necropsy revealed the presence of
nematodes in the pulmonary arteries of three animals. All parasites were mature
adults and the coproscopic examination showed the presence of eggs and L1 larvae
in all three positive animals. Light microscopy examination confirmed the
morphological and morphometric similarity of parasites to Angiostrongylus
daskalovi. SEM highlighted the typical angiostrongylid structure of the rays of
the copulatory bursa and the anterior extremity, with the presence of six sensory
papillae surrounding the mouth opening in which a triangular tooth was visible.
The first-stage larva (L1) of A. daskalovi is described here for the first time.
Histopathological examination of the lungs showed chronic interstitial verminous
pneumonia due to the presence of adult parasites. Molecular analysis showed 100 %
nucleotide similarity to an Angiostrongylus sp. isolate originating from a badger
from Spain, tentatively identified as A. daskalovi. CONCLUSIONS: Our study
unequivocally demonstrates the presence of A. daskalovi in European badgers from
Romania, provides the first description of the larvae and reveals new data about
the ultrastructure of adult parasites and their pathological impact, contributing
to the understanding of the phylogenetic relationships with other congeneric
species.
PMID- 27485119
TI - Quality of life effects of androgen deprivation therapy in a prostate cancer
cohort in New Zealand: can we minimize effects using a stratification based on
the aldo-keto reductase family 1, member C3 rs12529 gene polymorphism?
AB - BACKGROUND: Androgen deprivation therapy (ADT) is an effective palliation
treatment in men with advanced prostate cancer (PC). However, ADT has well
documented side effects that could alter the patient's health-related quality of
life (HRQoL). The current study aims to test whether a genetic stratification
could provide better knowledge for optimising ADT options to minimize HRQoL
effects. METHODS: A cohort of 206 PC survivors (75 treated with and 131 without
ADT) was recruited with written consent to collect patient characteristics,
clinical data and HRQoL data related to PC management. The primary outcomes were
the percentage scores under each HRQoL subscale assessed using the European
Organisation for Research and Treatment of Cancer Quality of Life questionnaires
(QLQ-C30 and PR25) and the Depression Anxiety Stress Scales developed by the
University of Melbourne, Australia. Genotyping of these men was carried out for
the aldo-keto reductase family 1, member C3 (AKR1C3) rs12529 single nucleotide
polymorphism (SNP). Analysis of HRQoL scores were carried out against ADT
duration and in association with the AKR1C3 rs12529 SNP using the generalised
linear model. P-values <0 . 05 were considered significant, and were further
tested for restriction with Bonferroni correction. RESULTS: Increase in hormone
treatment-related effects were recorded with long-term ADT compared to no ADT.
The C and G allele frequencies of the AKR1C3rs12529 SNP were 53.4 % and 46.6 %
respectively. Hormone treatment-related symptoms showed an increase with ADT when
associated with the AKR1C3 rs12529 G allele. Meanwhile, decreasing trends on
cancer-specific symptoms and increased sexual interest were recorded with no ADT
when associated with the AKR1C3 rs12529 G allele and reverse trends with the C
allele. As higher incidence of cancer-specific symptoms relate to cancer
retention it is possible that associated with the C allele there could be higher
incidence of unresolved cancers under no ADT options. CONCLUSIONS: If these
findings can be reproduced in larger homogeneous cohorts, a genetic
stratification based on the AKR1C3 rs12529 SNP, can minimize ADT-related HRQoL
effects in PC patients. Our data additionally show that with this stratification
it could also be possible to identify men needing ADT for better oncological
advantage.
PMID- 27485120
TI - "Did you ever drink more?" A detailed description of pregnant women's drinking
patterns.
AB - BACKGROUND: This paper presents drinking patterns in a prospective study of a
population-based cohort of 1570 pregnant women using a combination of dose and
timing to give best estimates of prenatal alcohol exposure (PAE). Novel
assessments include women's special occasion drinking and alcohol use prior to
pregnancy recognition. METHODS: Information on up to nine types of alcoholic
drink, with separate frequencies and volumes, including drinking on special
occasions outside a 'usual' pattern, was collected for the periconceptional
period and at four pregnancy time points. Weekly total and maximum alcohol
consumption on any one occasion was calculated and categorised. Drinking patterns
are described in the context of predictive maternal characteristics. RESULTS:
41.3 % of women did not drink during pregnancy, 27 % drank in first trimester
only; most of whom stopped once they realised they were pregnant (87 %). When
compared to women who abstained from alcohol when pregnant, those who drank in
the first trimester only were more likely to have an unplanned pregnancy and not
feel the effects of alcohol quickly. Almost a third of women continued to drink
alcohol at some level throughout pregnancy (27 %), around half of whom never
drank more than at low or moderate levels. When compared with abstainers and to
women who only drank in trimester one, those who drank throughout pregnancy
tended to be in their early to mid-thirties, smoke, have a higher income and
educational attainment. Overall, almost one in five women (18.5 %) binge drank
prior to pregnancy recognition, a third of whom were identified with a question
about 'special occasion' drinking. Women whose age at first intoxication was less
than 18 years (the legal drinking age in Australia), were significantly more
likely to drink in pregnancy and at binge levels prior to pregnancy recognition.
CONCLUSIONS: We have identified characteristics of pregnant women who either
abstain, drink until pregnancy awareness or drink throughout pregnancy. These may
assist in targeting strategies to enhance adherence to an abstinence policy and
ultimately allow for appropriate follow-up and interpretation of adverse child
outcomes. Our methodology also produced important information to reduce
misclassification of occasional binge drinking episodes and ensure clearly
defined comparison groups.
PMID- 27485121
TI - LIMT is a novel metastasis inhibiting lncRNA suppressed by EGF and downregulated
in aggressive breast cancer.
AB - Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in
pathogenesis, including cancer. Recently, lncRNAs have been implicated in
progression of specific subtypes of breast cancer. One aggressive, basal-like
subtype associates with increased EGFR signaling, while another, the HER2
enriched subtype, engages a kin of EGFR Based on the premise that EGFR-regulated
lncRNAs might control the aggressiveness of basal-like tumors, we identified
multiple EGFR-inducible lncRNAs in basal-like normal cells and overlaid them with
the transcriptomes of over 3,000 breast cancer patients. This led to the
identification of 11 prognostic lncRNAs. Functional analyses of this group
uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly
conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors,
and the low expression of which predicts poor patient prognosis. Interestingly,
EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at
the respective promoter. We also find that LIMT inhibits extracellular matrix
invasion of mammary cells in vitro and tumor metastasis in vivo In conclusion,
lncRNAs dynamically regulated by growth factors might act as novel drivers of
cancer progression and serve as prognostic biomarkers.
PMID- 27485123
TI - MRI-based ACL graft maturity does not predict clinical and functional outcomes
during the first year after ACL reconstruction.
AB - PURPOSE: To determine whether magnetic resonance image (MRI)-based graft maturity
predicts clinical and functional scores during the first year after ACL
reconstruction. METHODS: Patients with unilateral ACL reconstruction were
prospectively invited to participate in this study, and they were examined using
a 3.0-T MRI scan at 3, 6, and 12 months after the operation. Clinical
examinations were performed on the same day, including subjective functional
examinations, physical examinations and the KT-1000 test. MRI measurements were
focused on the graft signal intensity of the ACL graft using the signal/noise
quotient value from a region of interest analysis. RESULTS: Finally, a total of
38 participants with ACL reconstruction were recruited for this study, including
21 with autograft tendons and 17 with allograft tendons. Generally, the
signal/noise quotient values of the ACL grafts increased from 3 to 6 months and
then decreased from 6 to 12 months. There was no significant association between
graft signal/noise quotient value and IKDC, Lysholm, or Tegner scores at each
time point. Graft signal/noise quotient value had a significant positive
association with ATTD for the cohort (p = 0.002) and for the autograft group (p =
0.004) at 3 months. However, there was no significant association between graft
signal/noise quotient value and ATTD at 6 or 12 months, respectively. CONCLUSION:
The MRI-based graft maturity does not have the ability to predict clinical and
functional outcomes in patients at the first-year follow-up. Graft maturity
should not be used as an objective test to determine the appropriate time to
return to sports during the first year after ACL reconstruction. The results from
this study will allow clinicians to determine graft-specific health to determine
whether the graft is healed enough to return to sports during the first
postoperative year. LEVEL OF EVIDENCE: III.
PMID- 27485122
TI - miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in
Alzheimer's brain.
AB - microRNA-132 (miR-132) is involved in prosurvival, anti-inflammatory and memory
promoting functions in the nervous system and has been found consistently
downregulated in Alzheimer's disease (AD). Whether and how miR-132 deficiency
impacts AD pathology remains, however, unaddressed. We show here that miR-132
loss exacerbates both amyloid and TAU pathology via inositol 1,4,5-trisphosphate
3-kinase B (ITPKB) upregulation in an AD mouse model. This leads to increased
ERK1/2 and BACE1 activity and elevated TAU phosphorylation. We confirm
downregulation of miR-132 and upregulation of ITPKB in three distinct human AD
patient cohorts, indicating the pathological relevance of this pathway in AD.
PMID- 27485124
TI - Anteroposterior translation and range of motion after total knee arthroplasty
using posterior cruciate ligament-retaining versus posterior cruciate ligament
substituting prostheses.
AB - PURPOSE: It is still controversial whether anteroposterior (AP) translation
magnitude after total knee arthroplasty (TKA) affects clinical outcomes,
particularly range of motion (ROM). This study examined the following two
questions: (1) are AP translations at the mid- and long-term follow-up different
for knees within the same patient treated with posterior cruciate ligament
retaining (PCLR) versus posterior cruciate ligament-substituting (PCLS) mobile
bearing TKA prosthesis designs? (2) Is the ROM at the mid- and long-term follow
up for knees treated with PCLR and PCLS designs correlated with the AP
translation? METHODS: Thirty-seven patients undergoing sequential bilateral TKA
for osteoarthritis were prospectively enrolled. Patients received a PCLR implant
in one knee and a PCLS implant in the other and were followed-up for an average
9.8 +/- 3.2 years. The AP translations at 30 degrees and 75 degrees of knee
flexion and the ROM of both knees were assessed. RESULTS: The implant design (p <
0.001), but not flexion angle (n.s.), had a significant effect on AP translation.
AP translation values were larger in PCLR knees than in PCLS knees at both
flexion angles (p < 0.0001). The ROM at the final follow-up in the two implant
designs was similar (both 115 degrees , n.s.). There was a weak correlation
between ROM and AP translation at 30 degrees in the PCLR knees (r = 0.397, p =
0.015), but no correlation at 75 degrees or in the PCLS knees. CONCLUSIONS:
Differently constrained prosthesis designs resulted in significantly different AP
translational values within the same patient. This indicates that achieving good
clinical outcomes and ROM after TKA may not be strongly influenced by the
specifics of each patient's anatomical characteristics, but instead by knee
constrainment. Clinically, this means that surgeons should familiarize themselves
with the AP translation of the implant being used, as this may be the most
important factor for optimizing outcomes after mobile-bearing TKA. Level of
evidence II, prospective, comparative study.
PMID- 27485125
TI - Comparison between cylindrical axis-reference and articular surface-reference
femoral bone cut for total knee arthroplasty.
AB - PURPOSE: Reproducing a functional flexion-extension axis (FEA) of the femur is
key to achieving successful collateral ligament balance and joint line in total
knee arthroplasty (TKA). This study compared the feasibility of cylindrical axis
(CA)-reference bone cut and articular surface-reference bone cuts in reproducing
the FEA for Japanese osteoarthritis patients. METHODS: The study enrolled 122
knees from 86 patients who underwent primary TKA due to grade III or IV
osteoarthritis. Data from pre-operative CT were reconstructed into three
dimensional (3D) models using 3D-planning software. Cylindrical radii of the
condyles were measured, and femoral bone cut angles relative to anatomical
landmarks were determined in the coronal and axial reference planes based on CA
reference and articular surface-reference methods. RESULTS: Mean cylindrical
radii for medial and lateral femoral condyles were 17.4 +/- 1.6 and 17.3 +/- 1.4
mm, respectively. Of the 122 knees, 46 exhibited >1 mm of difference between
condyles. Fifty-three and 22 knees exhibited >2 degrees of angular difference
between CA-reference and articular surface-reference bone cuts in the coronal and
axial planes. Mean angle of the CA and surgical epicondylar axis in 3D space was
4.6 +/- 2.1 degrees . As practical parameters for TKA, the angle between CA and
IM rod was significantly larger than that between the distal articular surface
line and IM rod in the coronal plane (p < 0.0001), indicating that CA-reference
involves a smaller valgus bone cut of the distal femur than articular surface
reference. CONCLUSIONS: CA-reference bone cut of the femur is preferable to
articular surface-reference bone cut for reproducing FEA in Japanese OA patients,
in whom more than one-third of knees exhibited asymmetry of radii between medial
and lateral condyles. In clinical practice, the CA-reference bone cut represents
a good technical option for kinematically aligned TKA in the Japanese population.
PMID- 27485126
TI - Natural history and risk stratification of patients undergoing non-invasive
ventilation in a non-ICU setting for severe COPD exacerbations.
PMID- 27485127
TI - Determinants of a successful problem list to support the implementation of the
problem-oriented medical record according to recent literature.
AB - BACKGROUND: A problem-oriented approach is one of the possibilities to organize a
medical record. The problem-oriented medical record (POMR) - a structured
organization of patient information per presented medical problem- was introduced
at the end of the sixties by Dr. Lawrence Weed to aid dealing with the
multiplicity of patient problems. The problem list as a precondition is the
centerpiece of the problem-oriented medical record (POMR) also called problem
oriented record (POR). Prior to the digital era, paper records presented a flat
list of medical problems to the healthcare professional without the features that
are possible with current technology. In modern EHRs a POMR based on a structured
problem list can be used for clinical decision support, registries, order
management, population health, and potentially other innovative functionality in
the future, thereby providing a new incentive to the implementation and use of
the POMR. METHODS: On both 12 May 2014 and 1 June 2015 a systematic literature
search was conducted. From the retrieved articles statements regarding the POMR
and related to successful or non-successful implementation, were categorized.
Generic determinants were extracted from these statements. RESULTS: In this
research 38 articles were included. The literature analysis led to 12 generic
determinants: clinical practice/reasoning, complete and accurate problem list,
data structure/content, efficiency, functionality, interoperability, multi
disciplinary, overview of patient information, quality of care, system support,
training of staff, and usability. CONCLUSIONS: Two main subjects can be
distinguished in the determinants: the system that the problem list and POMR is
integrated in and the organization using that system. The combination of the two
requires a sociotechnical approach and both are equally important for successful
implementation of a POMR. All the determinants have to be taken into account, but
the weight given to each of the determinants depends on the organizationusing the
problem list or POMR.
PMID- 27485128
TI - Characterization and quantification of dissolved organic carbon releases from
suspended and sedimented leaf fragments and of residual particulate organic
matter.
AB - Bank filtration is a powerful and established barrier for pathogens and organic
pollutants. The aerobic degradation of the pollutants competes with the microbial
respiration of dissolved and particulate organic matter (DOC and POC). The fate
of terrestrial POC (tPOC) in bank filtration is currently not fully understood.
In the present study, fallen leaves of different local trees were milled,
characterized and investigated as tPOC in both batch and column experiments. The
respective contents of carbon and nitrogen differed slightly, but the different
leaves released significantly different DOC fractions as determined by size
exclusion chromatography. While high molecular weight biopolymers were degraded
by indigenous microorganisms, humic substances were not degraded within 96days in
batch experiments. DOC release and POC wash-out in column experiments led to a
slight decrease of tPOC depositions, but more than 80% of the initial tPOC
remained after 54days thus representing a long-term organics reservoir for
microbial respiration. The release of humic substances from autumnal leaf litter
inputs is a plausible explanation for comparably high DOC concentrations
(approximately 4.5mg/L) in Berlin drinking water that mainly originates from lake
bank filtration.
PMID- 27485129
TI - Engineered nanomaterial-mediated changes in the metabolism of terrestrial plants.
AB - Engineered nanomaterials (ENMs) possess remarkable physicochemical
characteristics suitable for different applications in medicine, pharmaceuticals,
biotechnology, energy, cosmetics and electronics. Because of their ultrafine size
and high surface reactivity, ENMs can enter plant cells and interact with
intracellular structures and metabolic pathways which may produce toxicity or
promote plant growth and development by diverse mechanisms. Depending on their
type and concentration, ENMs can have positive or negative effects on
photosynthesis, photochemical fluorescence and quantum yield as well as
photosynthetic pigments status of the plants. Some studies have shown that ENMs
can improve photosynthetic efficiency via increasing chlorophyll content and
light absorption and also broadening the spectrum of captured light, suggesting
that photosynthesis can be nano-engineered for harnessing more solar energy. Both
up- and down-regulation of primary metabolites such as proteins and carbohydrates
have been observed following exposure of plants to various ENMs. The potential
capacity of ENMs for changing the rate of primary metabolites lies in their close
relationship with activation and biosynthesis of the key enzymes. Several classes
of secondary metabolites such as phenolics, flavonoids, and alkaloids have been
shown to be induced (mostly accompanied by stress-related factors) in plants
exposed to different ENMs, highlighting their great potential as elicitors to
enhance both quantity and quality of biologically active secondary metabolites.
Considering reports on both positive and negative effects of ENMs on plant
metabolism, in-depth studies are warranted to figure out the most appropriate
ENMs (type, size and optimal concentration) in order to achieve the desirable
effect on specific metabolites in a given plant species. In this review, we
summarize the studies performed on the impacts of ENMs on biosynthesis of plant
primary and secondary metabolites and mention the research gaps that currently
exist in this field.
PMID- 27485130
TI - Evaluation of different approaches to describe the sorption and desorption of
phosphorus in soils on experimental data.
AB - Phosphorus is an essential element to enhance the needed increase in crop
production in the forthcoming century. On the other hand environmental losses of
phosphorus cause eutrophication of surface waters. Both problems call for
reliable models to predict the behaviour of phosphorus in agricultural soils. In
this study the performances of five different sorption approaches were evaluated.
The ultimate aim was to identify the most suitable concept for large scale
predictions of P dynamics in soils, in terms of a high comparability between
observations and predictions with a minimum amount of input data. The model
results were compared with unique data from long term (10-15years) experimental
field studies of grassland including situations with P mining, equilibrium P
fertilization and P surpluses and a pot experiment with P mining. The model
performance was evaluated while using site specific constants and generic
constants for adsorption and desorption. Three rate limited models (DPPS,
INITIATOR and ANIMO) showed good performance when site specific constants were
used but the performance of the equilibrium model (NEWS-Dynamic) was reasonably
comparable. Model performance was better for experiments with a P surplus than
for P mining and was also better for sandy soils as compared to clay and peat
soils. However, long term desorption rates had to be calibrated for each
application rate. The performance of all models declined when generic data were
used. We conclude that none of the included models properly describe what happens
when the soil changes its P status, considering that parameterization needs to be
treatment-specific to obtain reliable predictions. Considering this flaw, models
of intermediate complexity, including both equilibrium and rate limited sorption,
and a limited data demand, like DPPS and INITIATOR, seem most suited for regional
model application.
PMID- 27485131
TI - Low-level environmental arsenic exposure correlates with unexplained male
infertility risk.
AB - Humans are exposed to arsenic via drinking water, dietary intake and inhaled
particulates. Endemic chronic arsenic exposure related reproductive toxicity is
well documented, but the effect of low-level general environmental arsenic
exposure on unexplained male infertility (UMI) remains unclear. In this case
control study, we aimed to investigate the relationship between non-geogenic
environmental arsenic exposure and UMI risk. One hundred and one infertile men
with normal semen as cases and sixty one fertile men as controls were recruited.
Five urinary arsenic species: pentavalent arsenate (Asi(V)), trivalent arsenite
(Asi(III)), methylated to monomethylarsonic acid (MMA(V)), dimethylarsinic acid
(DMA(V)), arsenobetaine (AsB) were quantitatively measured by liquid
chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS). To
assess the semen quality, semen volume, sperm concentration, total motility, and
progressive motility were measured. The nonparametric Mann-Whitney U test was
used to compare the differences of arsenic species and index between the case and
the control group; we observed that concentrations of Asi(V), AsB, MMA(V),
DMA(V), total inorganic As and total As were significantly higher in the cases
than the controls. The urine Asi(V) level increased more than twenty folds in
case group. Moreover, higher redox index (Asi(V)/Asi(III)) and lower primary
arsenic methylation index (PMI=MMA(V)/Asi) were observed for case group.
Furthermore, through the logistic regression analysis, we observed that the urine
Asi(V) level and PMI were most significantly associated with UMI risk among the
observations. Specifically, in comparison to the first quartile, the subjects
with higher Asi(V) levels were more likely to exhibit UMI with increasing
adjusted odds ratios (AORs) (adjusted by age, body mass index, drinking status
and smoking status) of 8.39 [95% confidence interval (CI), 2.59-27.17], 13.12
(95% CI, 3.44-50.12) and 36.51 (95% CI, 8.25-161.66) at the second, third and
fourth quartiles, respectively. Also a concentration-dependent decrease of AOR
was also observed for PMI in comparison to the fourth quartile: 15.43 [95% CI,
4.28-55.69], 9.69 (95% CI, 2.78-33.78) and 6.93 (95% CI, 2.21-21.76) at the
first, second and third quartiles, respectively. These findings provide evidences
that low-level environmental arsenic exposure was positively associated with UMI
risk.
PMID- 27485132
TI - Playing Action Video Games Improves Visuomotor Control.
AB - Can playing action video games improve visuomotor control? If so, can these games
be used in training people to perform daily visuomotor-control tasks, such as
driving? We found that action gamers have better lane-keeping and visuomotor
control skills than do non-action gamers. We then trained non-action gamers with
action or nonaction video games. After they played a driving or first-person
shooter video game for 5 or 10 hr, their visuomotor control improved
significantly. In contrast, non-action gamers showed no such improvement after
they played a nonaction video game. Our model-driven analysis revealed that
although different action video games have different effects on the sensorimotor
system underlying visuomotor control, action gaming in general improves the
responsiveness of the sensorimotor system to input error signals. The findings
support a causal link between action gaming (for as little as 5 hr) and
enhancement in visuomotor control, and suggest that action video games can be
beneficial training tools for driving.
PMID- 27485133
TI - Why Do People Tend to Infer "Ought" From "Is"? The Role of Biases in Explanation.
AB - People tend to judge what is typical as also good and appropriate-as what ought
to be. What accounts for the prevalence of these judgments, given that their
validity is at best uncertain? We hypothesized that the tendency to reason from
"is" to "ought" is due in part to a systematic bias in people's (nonmoral)
explanations, whereby regularities (e.g., giving roses on Valentine's Day) are
explained predominantly via inherent or intrinsic facts (e.g., roses are
beautiful). In turn, these inherence-biased explanations lead to value-laden
downstream conclusions (e.g., it is good to give roses). Consistent with this
proposal, results from five studies (N = 629 children and adults) suggested that,
from an early age, the bias toward inherence in explanations fosters inferences
that imbue observed reality with value. Given that explanations fundamentally
determine how people understand the world, the bias toward inherence in these
judgments is likely to exert substantial influence over sociomoral understanding.
PMID- 27485134
TI - The Bitter Truth About Sugar and Willpower: The Limited Evidential Value of the
Glucose Model of Ego Depletion.
AB - The idea behind ego depletion is that willpower draws on a limited mental
resource, so that engaging in an act of self-control impairs self-control in
subsequent tasks. To present ego depletion as more than a convenient metaphor,
some researchers have proposed that glucose is the limited resource that becomes
depleted with self-control. However, there have been theoretical challenges to
the proposed glucose mechanism, and the experiments that have tested it have
found mixed results. We used a new meta-analytic tool, p-curve analysis, to
examine the reliability of the evidence from these experiments. We found that the
effect sizes reported in this literature are possibly influenced by publication
or reporting bias and that, even within studies yielding significant results, the
evidential value of this research is weak. In light of these results, and pending
further evidence, researchers and policymakers should refrain from drawing any
conclusions about the role of glucose in self-control.
PMID- 27485135
TI - Molecular Programming of Tumor-Infiltrating CD8+ T Cells and IL15 Resistance.
AB - Despite clinical potential and recent advances, durable immunotherapeutic
ablation of solid tumors is not routinely achieved. IL15 expands natural killer
cell (NK), natural killer T cell (NKT) and CD8(+) T-cell numbers and engages the
cytotoxic program, and thus is under evaluation for potentiation of cancer
immunotherapy. We found that short-term therapy with IL15 bound to soluble IL15
receptor alpha-Fc (IL15cx; a form of IL15 with increased half-life and activity)
was ineffective in the treatment of autochthonous PyMT murine mammary tumors,
despite abundant CD8(+) T-cell infiltration. Probing of this poor responsiveness
revealed that IL15cx only weakly activated intratumoral CD8(+) T cells, even
though cells in the lung and spleen were activated and dramatically expanded.
Tumor-infiltrating CD8(+) T cells exhibited cell-extrinsic and cell-intrinsic
resistance to IL15. Our data showed that in the case of persistent viral or tumor
antigen, single-agent systemic IL15cx treatment primarily expanded antigen
irrelevant or extratumoral CD8(+) T cells. We identified exhaustion, tissue
resident memory, and tumor-specific molecules expressed in tumor-infiltrating
CD8(+) T cells, which may allow therapeutic targeting or programming of specific
subsets to evade loss of function and cytokine resistance, and, in turn, increase
the efficacy of IL2/15 adjuvant cytokine therapy. Cancer Immunol Res; 4(9); 799
811. (c)2016 AACR.
PMID- 27485136
TI - Therapeutic HPV Cancer Vaccine Targeted to CD40 Elicits Effective CD8+ T-cell
Immunity.
AB - Human papillomavirus (HPV), particularly HPV16 and HPV18, can cause cancers in
diverse anatomical sites, including the anogenital and oropharyngeal (throat)
regions. Therefore, development of safe and clinically effective therapeutic
vaccines is an important goal. Herein, we show that a recombinant fusion protein
of a humanized antibody to CD40 fused to HPV16.E6/7 (alphaCD40-HPV16.E6/7) can
evoke HPV16.E6/7-specific CD8+ and CD4+ T-cell responses in head-and-neck cancer
patients in vitro and in human CD40 transgenic (hCD40Tg) mice in vivo The
combination of alphaCD40-HPV16.E6/7 and poly(I:C) efficiently primed HPV16.E6/7
specific T cells, particularly CD8+ T cells, in hCD40Tg mice. Inclusion of
montanide enhanced HPV16.E6/7-specific CD4+, but not CD8+, T-cell responses.
Poly(I:C) plus alphaCD40-HPV16.E6/7 was sufficient to mount both preventative and
therapeutic immunity against TC-1 tumors in hCD40Tg mice, significantly
increasing the frequency of HPV16-specific CD8+ CTLs in the tumors, but not in
peripheral blood. In line with this, tumor volume inversely correlated with the
frequency of HPV16.E6/7-specific CD8+ T cells in tumors, but not in blood. These
data suggest that CD40-targeting vaccines for HPV-associated malignancies can
provide a highly immunogenic platform with a strong likelihood of clinical
benefit. Data from this study offer strong support for the development of CD40
targeting vaccines for other cancers in the future. Cancer Immunol Res; 4(10);
823-34. (c)2016 AACR.
PMID- 27485137
TI - Analyses of Pretherapy Peripheral Immunoscore and Response to Vaccine Therapy.
AB - Tumor immunoscore analyses, especially for primary colorectal cancer and melanoma
lesions, provide valuable prognostic information. Metastatic lesions of many
carcinoma types, however, are often not easily accessible. We hypothesized that
immune cells in peripheral blood may differ among individual patients with
metastatic disease, which, in turn, may influence their response to
immunotherapy. We thus analyzed immune cell subsets within peripheral blood
mononuclear cells to determine if a "peripheral immunoscore" could have any
prognostic significance for patients before receiving immunotherapy. Patients
with metastatic breast cancer were randomly assigned to receive docetaxel +/-
PANVAC vaccine. In another trial, prostate cancer patients with metastatic bone
lesions were randomly assigned to receive a bone-seeking radionuclide +/-
PROSTVAC vaccine. Predefined analyses of "classic" immune cell types (CD4, CD8,
natural killer cells, regulatory T cells, myeloid-derived suppressor cells, and
ratios) revealed no differences in progression-free survival (PFS) for either arm
in both trials. Predefined analyses of refined immune cell subsets for which a
biologic function had been previously reported also showed no significant
prognostic value in PFS for patients receiving either docetaxel or radionuclide
alone; however, in patients receiving these agents in combination with vaccine,
the peripheral immunoscore of refined subsets revealed statistically significant
differences in PFS (P < 0.001) for breast cancer patients receiving docetaxel
plus vaccine, and in prostate cancer patients receiving radionuclide plus vaccine
(P = 0.004). Larger randomized studies will be required to validate these
findings. These studies, however, provide the rationale for the evaluation of
refined immune cell subsets to help determine which patients may benefit most
from immunotherapy. Cancer Immunol Res; 4(9); 755-65. (c)2016 AACR.
PMID- 27485138
TI - Survival of neonates and predictors of their mortality in Tigray region, Northern
Ethiopia: prospective cohort study.
AB - BACKGROUND: Neonatal mortality accounts for an estimated 2.8 million deaths
worldwide, which constitutes 44 % of under-5-mortality and 60 % of infant
mortality. Neonatal mortality predictors vary by country with the availability
and quality of health care. Therefore, aim of this study was to estimate survival
time and identify predictors of neonatal mortality in Tigray region, northern
Ethiopia. METHOD: A prospective cohort study design was carried out among a
cohort of neonates delivered in seven hospitals of Tigray from April to July,
2014 and followed up for a total of 28 days. Data were collected by interviewing
mothers using structured questionnaires and assessments of the neonate and
mothers by midwives. Kaplan-Meier, Log rank test and Cox-proportional hazard
regressions were used. STATA V-11 program was used for data entry, cleaning and
analysis. RESULTS: From 1152 neonates, 68 died (neonatal mortality rate 62.5/1000
live births), 73.52 % of the neonates died within 7 days, 60 were lost to follow
up and the percentage of survival at 28 days was 93.96 % (95 % CI: 92.4, 95.2 %).
Predictors of neonatal mortality were: normal birth weight (AHR: 0.45, 95 % CI:
0.24, 0.84), not initiating exclusive breastfeeding (AHR: 7.5, 95 % CI: 3.77,
15.05), neonatal complications (AHR: 0.14, 95 % CI 0.07, 0.29), maternal
complications (AHR: 0.37, 95 % CI: 0.22, 0.63) and proximity (AHR: 2.5, 95 % CI:
1.29, 4.91). CONCLUSION: Neonatal mortality is unacceptably very high. Managing
complications and low birth weight, initiating exclusive breast feeding,
improving quality of services and ensuring a continuum of care are recommended to
increase survival of neonates.
PMID- 27485139
TI - Neuroprotective effect of ginsenoside Rg1 prevents cognitive impairment induced
by isoflurane anesthesia in aged rats via antioxidant, anti-inflammatory and anti
apoptotic effects mediated by the PI3K/AKT/GSK-3beta pathway.
AB - Ginsenoside Rg1 is the primary active substance in ginseng, and it has multiple
pharmacological actions. Investigations on the pharmacologic action of
ginsenoside Rg1 have developed, with a particular focus on the regulation of
metabolism. The present study hypothesized that the neuroprotective effects of
ginsenoside Rg1 prevent cognitive impairment induced by isoflurane anesthesia via
antioxidant, anti-inflammatory and anti-apoptotic effects, mediated by the
phosphoinositide 3-kinase (PI3K)/AKT/glycogen synthase kinase-3beta (GSK-3beta)
pathway in aged rats. Sprague-Dawley rats were divided into isoflurane and
ginsenoside Rg1 groups and were treated with 20 mg/kg ginsenoside Rg1 for 7 days.
Morris water maze was performed to analyze the cognitive function of the rats.
Enzyme-linked immunosorbent assays were used to analyze the levels of
malondialdehyde, glutathione, interleukin (IL)-1beta, IL-6 and caspase 3. The
protein expression levels of AKT, GSK 3beta, p21WAF1/CIP1 and p53 were measured
using western blot analysis. Ginsenoside Rg1 significantly improved cognitive
function, and exhibited antioxidant and anti-inflammatory effects, demonstrating
the neuroprotective effects of ginsenoside Rg1 against the effect of isoflurane
anesthesia in the rats. In addition, ginsenoside Rg1 significantly reduced
caspase-3 activity, upregulated the expression of PI3K/AKT/GSK-3beta and
downregulated the mRNA expression levels of p21WAF1/CIP1 and p53 in the aged rats
exposed to isoflurane anesthesia. The data obtained in the present study provided
evidence that the neuroprotective effects of ginsenoside Rg1 prevented the
cognitive impairment induced by isoflurane anesthesia via antioxidant, anti
inflammatory and anti-apoptotic effects, mediated by the PI3K/AKT/GSK-3beta
pathway.
PMID- 27485140
TI - Implications of different criteria for percutaneous coronary intervention-related
myocardial infarction on study results of three large phase III clinical trials:
The CHAMPION experience.
AB - AIMS: The purpose of this study was to test whether different results between
Cangrelor versus standard therapy to acHieve optimal Management of Platelet
InhibitiON (CHAMPION) PCI/PLATFORM and PHOENIX trials are due in part to
different definitions of percutaneous coronary intervention (PCI)-related
myocardial infarction (MI). METHODS AND RESULTS: In patients with acute coronary
syndrome (ACS), the definition of MI was identical in CHAMPION PCI and PLATFORM
and did not require an assessment of baseline cardiac biomarker status, while in
PHOENIX specific MI criteria were associated with different patient
presentations. The same MI criteria were used in PCI, PLATFORM, and PHOENIX for
patients with stable angina. Logistic regression assessed the effect of cangrelor
on MI (PCI- and non-PCI related) in the combined PCI/PLATFORM population and in
PHOENIX. Consistency of cangrelor's effect in PCI/PLATFORM and in PHOENIX in
patients with stable angina and in those with an ACS (with or without ST
elevation) was evaluated. Overall, the incidence of PCI-related MI at 48 h was
6.3% in PCI/PLATFORM and 4.0% in PHOENIX. In patients with ACS, MI incidence was
6.4% in PCI/PLATFORM and 1.7% in PHOENIX, and 6.3% and 5.6%, respectively in
stable angina patients. Cangrelor's effect on PCI-related MI differed between
PCI/PLATFORM (odds ratio (OR) 1.03, 95% confidence interval (CI) 0.90-1.17) and
PHOENIX (OR 0.80, 95% CI 0.66-0.98) with pINT=0.04. This difference was mostly
evident in patients with ACS ( pINT= 0.06) while the effect was consistent in
patients with stable angina ( pINT=0.81). Results were similar when all MIs were
analyzed. CONCLUSIONS: The definition of PCI-related MI has important
implications for event rates, treatment effect, and study results. This
illustrates the importance of a rigorous assessment of PCI-related MI in clinical
trials of patients with an ACS.
PMID- 27485141
TI - Editor's Choice-Sex differences in young patients with acute myocardial
infarction: A VIRGO study analysis.
AB - AIMS: Young women with acute myocardial infarction (AMI) have a higher risk of
adverse outcomes than men. However, it is unclear how young women with AMI are
different from young men across a spectrum of characteristics. We sought to
compare young women and men at the time of AMI on six domains of demographic and
clinical factors in order to determine whether they have distinct profiles.
METHODS AND RESULTS: Using data from Variation in Recovery: Role of Gender on
Outcomes of Young AMI Patients (VIRGO), a prospective cohort study of women and
men aged ?55 years hospitalized for AMI ( n = 3501) in the United States and
Spain, we evaluated sex differences in demographics, healthcare access,
cardiovascular risk and psychosocial factors, symptoms and pre-hospital delay,
clinical presentation, and hospital management for AMI. The study sample included
2349 (67%) women and 1152 (33%) men with a mean age of 47 years. Young women with
AMI had higher rates of cardiovascular risk factors and comorbidities than men,
including diabetes, congestive heart failure, chronic obstructive pulmonary
disease, renal failure, and morbid obesity. They also exhibited higher levels of
depression and stress, poorer physical and mental health status, and lower
quality of life at baseline. Women had more delays in presentation and presented
with higher clinical risk scores on average than men; however, men presented with
higher levels of cardiac biomarkers and more classic electrocardiogram findings.
Women were less likely to undergo revascularization procedures during
hospitalization, and women with ST segment elevation myocardial infarction were
less likely to receive timely primary reperfusion. CONCLUSIONS: Young women with
AMI represent a distinct, higher-risk population that is different from young
men.
PMID- 27485142
TI - Age-related commonalities and differences in the relationship between executive
functions and intelligence: Analysis of the NAB executive functions module and
WAIS-IV scores.
AB - Data from five subtests of the Executive Functions Module of the German
Neuropsychological Assessment Battery (NAB) and all ten core subtests of the
German Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) were used to
examine the relationship between executive functions and intelligence in a
comparison of two age groups: individuals aged 18-59 years and individuals aged
60-88 years. The NAB subtests Categories and Word Generation demonstrated a
consistent correlation pattern for both age groups. However, the NAB Judgment
subtest correlated more strongly with three WAIS-IV indices, the Full Scale IQ
(FSIQ), and the General Ability Index (GAI) in the older adult group than in the
younger group. Additionally, in the 60-88 age group, the Executive Functions
Index (EFI) was more strongly correlated with the Verbal Comprehension Index
(VCI) than with the Perceptual Reasoning Index (PRI). Both age groups
demonstrated a strong association of the EFI with the FSIQ and the Working Memory
Index (WMI). The results imply the potential diagnostic utility of the Judgment
subtest and a significant relationship between executive functioning and
crystallized intelligence at older ages. Furthermore, it may be concluded that
there is a considerable age-independent overlap between the EFI and general
intelligence, as well as between the EFI and working memory.
PMID- 27485143
TI - Allantoin, a stress-related purine metabolite, can activate jasmonate signaling
in a MYC2-regulated and abscisic acid-dependent manner.
PMID- 27485144
TI - From nanoemulsions to self-nanoemulsions, with recent advances in self
nanoemulsifying drug delivery systems (SNEDDS).
AB - INTRODUCTION: Lipid-based drug delivery systems (LBDDS) are the most promising
technique to formulate the poorly water soluble drugs. Nanotechnology strongly
influences the therapeutic performance of hydrophobic drugs and has become an
essential approach in drug delivery research. Self-nanoemulsifying drug delivery
systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and
nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with
poor aqueous solubility. Areas covered: The review in its first part shortly
describes the LBDDS, nanoemulsions and clarifies the ambiguity between
nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS
and elaborates on the current developments and modifications in this area without
discussing their associated preparation techniques and excipient properties.
Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability
of poorly water soluble drugs. The stability of SNEDDS is further increased by
solidification. Controlled release and supersaturation can be achieved, and are
associated with increased patient compliance and improved drug loads,
respectively. Presence of biodegradable ingredients and ease of large-scale
manufacturing combined with a lot of 'drug-targeting opportunities' give SNEDDS a
clear distinction and prominence over other solubility enhancement techniques.
PMID- 27485146
TI - Field-induced dielectric response saturation in o-TaS3.
AB - We investigated dependence of the dielectric properties on temperature and
electric field below 50 K along the chain direction of o-TaS3. With external
electric field increase, two threshold features could be identified. For electric
fields somewhat larger than the lower threshold [Formula: see text], the
dielectric constant starts to decrease whereas the conductivity increases due to
the tunnelling of solitons. For higher external electric field we observe a
saturation of dielectric response and analyze that the possible reasons may be
related to the polarization behavior of charged solitons. With a decrease in
temperature, the effect of external field on the dielectric response of the
system weakens gradually and at 13 K it diminishes due to soliton freezing.
PMID- 27485145
TI - Ten-year alcohol consumption typologies and trajectories of C-reactive protein,
interleukin-6 and interleukin-1 receptor antagonist over the following 12 years:
a prospective cohort study.
AB - BACKGROUND: Moderate alcohol consumption is thought to confer cardiometabolic
protective effects. Inflammatory pathways are hypothesized to partly underlie
this association. OBJECTIVES: The aim of this study was to examine the
association between typologies of alcohol consumption and markers of
inflammation, and their rate of change over time. METHODS: Data were collected
from 8209 participants [69% men; mean age, 50 years (SD 6.1)] of the British
Whitehall II study. Alcohol consumption typologies were defined using up to three
measures during an approximately 10-year period spanning from 1985 to 1994 as (i)
stable nondrinkers, (ii) stable moderate drinkers (referent), (iii) stable heavy
drinkers, (iv) nonstable drinkers and (v) former drinkers. C-reactive protein
(CRP), interleukin (IL)-6 and IL-1 receptor antagonist (IL-1 RA) were measured up
to three times in the following 12 years. RESULTS: Stable moderate drinkers had
lower levels of CRP than stable nondrinkers, stable heavy drinkers, former
drinkers and nonstable drinkers, but there were no differences in the rate of
change in CRP over time between groups. Stable nondrinkers had higher levels of
IL-6 as did stable heavy drinkers; rates of change in IL-6 over time were also
increased in the latter group. Stable nondrinkers also had higher levels of IL-1
RA. These associations were robust to adjustment for confounding factors.
CONCLUSION: Our novel investigation of 10-year drinking typologies shows that
stable moderate alcohol consumption is associated with a long-term inflammatory
marker profile that is consistent with conferring a reduced risk of developing
coronary heart disease.
PMID- 27485147
TI - Circadian variation in clinical features and outcome of intracerebral hemorrhage:
The INTERACT studies.
AB - Previous studies consistently reported a diurnal variation in the occurrence of
intracerebral hemorrhage (ICH), with a morning peak. However, limited knowledge
exists on the circadian pattern of ICH severity and outcome. This study aimed to
determine possible associations between ICH onset time and admission severity and
90-day outcomes using the combined data set of the pilot and main-phase Intensive
blood pressure (BP) reduction in an acute cerebral hemorrhage trial (INTERACT).
The ICH onset time was categorized into three groups (1: 00:00-07:59; 2: 08:00
15:59; and 3: 16:00-23:59). We found an association between onset time and low
Glasgow Coma Scale score: aOR (time 1: 1.72, 95% CI 1.12-2.66; time 3: 1.95, 95%
CI 1.31-2.89, p = 0.003; in comparison to time 2). There was no association
between onset time and volume of ICH (adjusted p = 0.354) or 90-day outcomes of
death or major disability, and death and major disability separately (all
adjusted p > 0.4). The results showed that more severe cases of ICH patients,
defined by a reduced level of consciousness, had late afternoon to early morning
stroke onset, but this was unrelated to baseline hematoma volume or location.
There was no circadian influence on ICH clinical outcome.
PMID- 27485148
TI - Electrokinetic supercharging in nonaqueous capillary electrophoresis for online
preconcentration and determination of tamoxifen and its metabolites in human
plasma.
AB - An online preconcentration method, namely electrokinetic supercharging (EKS), was
evaluated for the determination of tamoxifen and its metabolites in human plasma
in nonaqueous capillary electrophoresis with ultraviolet detection (NACE-UV).
This method was comprehensively optimized in terms of the leading electrolyte
(LE) and terminating electrolyte (TE) injection lengths, as well as
electrokinetic sample injection time. The optimized EKS conditions employed were
as follows: hydrodynamic injection (HI) of 10mM potassium chloride as LE at
150mbar for 36s (4% of total capillary volume). The sample was injected at 10kV
for 300s, followed by HI of 10mM pimozide as TE at 150mbar for 36s (4% of total
capillary volume). Separation was performed in 7.5mM deoxycholic acid sodium
salt, 15mM acetic acid and 1mM 18-crown-6 in 100% methanol at +25kV with UV
detection at 205nm. Under optimized conditions, the sensitivity was enhanced
between 160- and 600-fold when compared with our previously developed method
based on HI at 150mbar for 12s. The detection limit of the method for tamoxifen
and its metabolites were 0.05-0.25ng/mL, with RSDs between 2.1% and 3.5%.
Recoveries in spiked human plasma were 95.6%-99.7%. A comparison was also made
between the proposed EKS approach and the standard field-amplified sample
injection (FASI) technique. EKS proved to be 3-5 times more sensitive than the
FASI. The new EKS method was applied to the analysis of tamoxifen and its
metabolites in plasma samples from breast cancer patients after liquid-liquid
extraction.
PMID- 27485149
TI - Pharmacokinetics of ketamine and three metabolites in Beagle dogs under
sevoflurane vs. medetomidine comedication assessed by enantioselective capillary
electrophoresis.
AB - Ketamine is often used for anesthesia in veterinary medicine. One possible
comedication is the sedative alpha2-agonist medetomidine. Advantages of that
combination are the compensation of side effects of the two drugs and the
anesthetic-sparing effect of medetomidine. In vitro studies showed that
medetomidine has an inhibitive effect on the formation of norketamine.
Norketamine is the first metabolite of ketamine and is also active. It is
followed by others like 6-hydroxynorketamine and 5,6-dehydronorketamine (DHNK).
In an in vivo pharmacokinetic study Beagle dogs under sevoflurane anesthesia
(mean end-tidal concentration 3.0+/-0.2%) or following medetomidine sedation
(450MUg/m2) received 4mg/kg racemic ketamine or 2mg/kg S-ketamine. Blood samples
were collected between 0 and 900min after drug injection. 50MUL aliquots of
plasma were pretreated by liquid-liquid extraction prior to analysis of the
reconstituted extracts with a robust enantioselective capillary electrophoresis
assay using highly sulfated gamma-cyclodextrin as chiral selector and
electrokinetic sample injection of the analytes from the extract across a short
buffer plug without chiral selector. Levels of S- and R-ketamine, S- and R
norketamine, (2S,6S)- and (2R,6R)-hydroxynorketamine and S- and R-DHNK were
determined. Data were analyzed with compartmental pharmacokinetic models which
included two compartments for the ketamine and norketamine enantiomers and a
single compartment for the DHNK and 6-hydroxynorketamine stereoisomers.
Medetomidine showed an effect on the formation and elimination of all
metabolites. Stereoselectivities were detected for 6-hydroxynorketamine and DHNK,
but not for ketamine and norketamine.
PMID- 27485150
TI - Development of tropine-salt aqueous two-phase systems and removal of hydrophilic
ionic liquids from aqueous solution.
AB - A novel aqueous two-phase systems (ATPS) composed of a small molecule organic
compound tropine and an organic or inorganic salt aqueous solution has been
developed for the first time. The phase behavior of tropine-salt ATPS was
systemically investigated and the phase equilibrium data were measured in
different temperatures and concentrations and correlated by the Merchuk equation
with satisfactory results. The detection of the conductivity and particle size
proved the formation of micelle in the process of forming tropine-salt ATPS. The
separation application of the ATPS was assessed with the removal of hydrophilic
benzothiazolium-based ionic liquids (ILs) from aqueous solution. The result
showed that ILs were effectively extracted into the top tropine-rich phase.
Finally, ILs in the top tropine-rich phase were further separated by the means of
adsorption-desorption with DM301 macroporous resin and ethanol. The method of
novel tropine-salt ATPS combined with adsorption-desorption is demonstrated a
promising alternative thought and approach for the removal or recovery of
hydrophilic compounds from aqueous media and also could provide a potential
application for bio-separation.
PMID- 27485151
TI - Gas chromatography fractionation platform featuring parallel flame-ionization
detection and continuous high-resolution analyte collection in 384-well plates.
AB - Gas chromatography (GC) is a superior separation technique for many compounds.
However, fractionation of a GC eluate for analyte isolation and/or post-column
off-line analysis is not straightforward, and existing platforms are limited in
the number of fractions that can be collected. Moreover, aerosol formation may
cause serious analyte losses. Previously, our group has developed a platform that
resolved these limitations of GC fractionation by post-column infusion of a trap
solvent prior to continuous small-volume fraction collection in a 96-wells plate
(Pieke et al., 2013 [17]). Still, this GC fractionation set-up lacked a chemical
detector for the on-line recording of chromatograms, and the introduction of trap
solvent resulted in extensive peak broadening for late-eluting compounds. This
paper reports advancements to the fractionation platform allowing flame
ionization detection (FID) parallel to high-resolution collection of a full GC
chromatograms in up to 384 nanofractions of 7s each. To this end, a post-column
split was incorporated which directs part of the eluate towards FID. Furthermore,
a solvent heating device was developed for stable delivery of preheated/vaporized
trap solvent, which significantly reduced band broadening by post-column
infusion. In order to achieve optimal analyte trapping, several solvents were
tested at different flow rates. The repeatability of the optimized GC fraction
collection process was assessed demonstrating the possibility of up-concentration
of isolated analytes by repetitive analyses of the same sample. The feasibility
of the improved GC fractionation platform for bioactivity screening of toxic
compounds was studied by the analysis of a mixture of test pesticides, which
after fractionation were subjected to a post-column acetylcholinesterase (AChE)
assay. Fractions showing AChE inhibition could be unambiguously correlated with
peaks from the parallel-recorded FID chromatogram.
PMID- 27485153
TI - Influences of Sex and Age on the Hematological Profile of the Jundia (Silver
Catfish) Rhamdia quelen.
AB - In this study, sex and age influenced the hematological profiles of Jundia
(Silver Catfish) Rhamdia quelen. Females showed lower levels of hemoglobin, young
fish increased lymphocyte counts, and older fish increased hematocrit values.
These results indicate that, depending on age and sex, the fish have disparate
hematological profiles. For this reason, it is important to consider the sex and
age of an R. quelen when examining the impact of environmental and management
factors on this species in terms of their hematological profiles. Received May
24, 2015; accepted March 24, 2016.
PMID- 27485152
TI - Prevalence of cardiovascular-related comorbidity in ankylosing spondylitis,
psoriatic arthritis and psoriasis in primary care: a matched retrospective cohort
study.
AB - The aim of this study is to compare the prevalence of cardiovascular (CVD)
related comorbidities in patients with ankylosing spondylitis (AS), psoriatic
arthritis (PsA) or psoriasis (Ps) in UK primary care against matched cohorts.
Matched retrospective cohort study used a primary care consultation database.
Three cohorts were constructed using all patients with a Read code diagnosis of
AS, PsA or Ps between 1999 and 2009; each cohort was then compared in a 1:4 ratio
to a matched cohort. The prevalence of CVD-related comorbidities (hypertension,
ischaemic heart disease, hyperlipidaemia and diabetes mellitus) were identified
by the first consultation of a comorbid Read code, in those with an inflammatory
condition of interest. The prevalence of CVD-related comorbidities was compared
between each inflammatory cohort and their matched cohort using Fisher's exact
test. Ninety-four AS, 106 PsA and 290 Ps patients were identified. Compared with
matched cohorts, the most prevalent CVD-related comorbidity in patients with AS
was hypertension (35 (37.2 %) vs. 96 matched (25.5 %), p = 0.03); this was also
the case for PsA (41 (38.7 %) vs. 114 matched (26.9 %), p = 0.02). No differences
were seen in the prevalence of other CVD-related comorbidities in those with AS,
PsA or Ps compared to their matched cohorts. Our findings provide UK comparisons
of CVD-related comorbidities in patients with AS, PsA and Ps alone; specifically,
demonstrating increased prevalence of hypertension in AS and PsA cohorts compared
to their matched cohorts. This further supports the argument for more evidence in
the need for screening and intervention around CVD comorbidities in inflammatory
conditions.
PMID- 27485154
TI - Effect of OATP-binding on the prediction of biliary excretion.
AB - 1. Biliary excretion of compounds is dependant on several transporter proteins
for the active uptake of compounds from the blood into the hepatocytes. Organic
anion-transporting polypeptides (OATPs) are some of the most abundant transporter
proteins in the sinusoidal membrane and have been shown to have substrate
specificity similar to the structural characteristics of cholephilic compounds.
2. In this study, we sought to use measures of OATP binding as predictors of
biliary excretion in conjunction with molecular descriptors in a quantitative
structure-activity relationship (QSAR) study. Percentage inhibitions of three
subtypes of OATPs were used as surrogate indicators of OATP substrates. Several
statistical modelling techniques were incorporated including classification and
regression trees, boosted trees, random forest and multivariate adaptive
regression splines (MARS) in order to first develop QSARs for the prediction of
OATP inhibition of compounds. The predicted OATP percentage inhibition using
selected models were then used as features of the QSAR models for the prediction
of biliary excretion of compounds in rat. 3. The results indicated that
incorporation of predicted OATP inhibition improves accuracy of biliary excretion
models. The best result was obtained from a simple regression tree that used
predicted OATP1B1 percentage inhibition at the root node of the tree.
PMID- 27485155
TI - "Knowing Your Status and Knowing Your Partner's Status Is Really Where It
Starts": A Qualitative Exploration of the Process by Which a Sexual Partner's HIV
Status Can Influence Sexual Decision Making.
AB - Gay and bisexual men are at disproportionate risk for human immunodeficiency
virus (HIV) infection. While prevention efforts often emphasize consistent condom
use, there is growing evidence that men are using seroadaptive safer-sex
strategies, such as serosorting and seropositioning. This qualitative analysis of
204 HIV-negative and HIV-positive gay and bisexual men explored the ways that a
sexual partner's HIV status can influence safer-sex strategies and sexual
decisions. The majority of the respondents reported that they were influenced by
their partners' HIV status. Those respondents who reported no influence discussed
adhering to safer-sex rules that were not dependent on partner status and a lack
of concern about HIV. Conversely, respondents who reported influence identified
three primary areas of influence: psychological impacts, partner preference and
selection, and specific behavioral intentions and strategies. A conceptual model
explicating a potential process by which respondents use partner serostatus
information in shaping sexual decisions is presented.
PMID- 27485156
TI - Phenotypic and genotypic characterization of enteroaggregative Escherichia coli
isolates from pediatric population in Pakistan.
AB - Enteroaggregative Escherichia coli (EAEC) are a leading cause of diarrhea among
children. The objective of this study was to define the frequency of EAEC among
diarrheal children from flood-affected areas as well as sporadic cases, determine
multidrug resistance, and evaluation of virulence using an in vivo model of
pathogenesis. Stool samples were collected from 225 diarrheal children from 2010
to 2011 from flood-affected areas as well as from sporadic cases in Pakistan.
Identified EAEC isolates were characterized by phylogrouping, antibiotic
resistance patterns including the extended-spectrum beta lactamase spectrum,
single nucleotide polymorphism detection in gyrA and parC, and virulence
potential using wax worm, G. mellonella. A total of 35 (12.5%) confirmed EAEC
isolates were identified among 225 E. coli isolates. EAEC isolates displayed high
resistance to tetracycline, ampicillin, and cefaclor. A total of 34.28% were ESBL
positive. Single nucleotide polymorphism detection revealed 37.14% and 68.57%
isolates were positive for SNPs in gyrA (A660 -T660 ) and parC (C330 -T330 ),
respectively. Phylogrouping revealed that B2 phylogroup was more prevalent among
all EAEC isolates tested followed by D, A, B1, and non-typeable (NT). Infection
of G. mellonella with EAEC showed that killing infective dose was 100% higher
than E. coli DH5 alpha control. EAEC are prevalent among Pakistani children with
diarrhea, they are highly resistant to antibiotics, and predominantly fall into
B2 phylogroup. Epidemiologic surveillance of EAEC and other E. coli pathotypes is
critical to assess not only the role of these pathogens in diarrheal disease but
also to determine the extent of multidrug resistance among the population.
PMID- 27485157
TI - Combination of collagen and fibronectin to design biomimetic interfaces: Do these
proteins form layer-by-layer assemblies?
AB - Layer-by-layer (LbL) assembly is a surface modification method which may bring
complexity to biointerfaces designed to control cell-material interactions. This
work aims at investigating the LbL assembly of two extracellular matrix proteins,
collagen (Col) and fibronectin (Fn), on polystyrene substrates. LbL assembly,
which is widely applied to polyelectrolytes, is not easily transferred to
proteins. Different buffers and conditions are tested, and LbL assembly is
compared to the simultaneous adsorption of Fn and Col. Build-up and properties of
the films are monitored using quartz crystal microbalance, ellipsometry, water
contact angle measurements, and atomic force microscopy. Results show that
denatured Col leads to smoother films, and that the addition of a
polyethyleneimine anchoring layer increases film thickness. A more regular
construction and thicker films are obtained with Hepes (pH 7.4) compared to other
buffers. However, the LbL assembly is not sustainable and stops after the
deposition of a few layers. Films obtained by simultaneous adsorption have lower
water contact angles, different morphologies, lower water content and are as
thick or thicker compared to the ones prepared by the LbL method. The present
work shows that collagen and fibronectin are not involved in a true LbL assembly
process. The obtained biointerfaces however exhibit different properties compared
to those obtained by the one-step adsorption of these proteins. These differences
could be exploited to control cell fate.
PMID- 27485158
TI - Mental health and breast cancer screening utilization among older Hispanic women.
AB - Considerable racial and ethnic differences exist in the way the burden of cancer
is experienced in the United States for older Hispanic women. This study utilized
data from the 2008 wave of the Health and Retirement Study to investigate the
mental health factors associated with older Hispanic women's participation in
breast cancer screening services. Logistic regression models were used. Findings
indicated that anxiety and positive affect were associated with a greater
likelihood of participating in breast cancer screening. Despite ongoing national
conversations, evidence indicates there is agreement that underserved women need
to be screened, particularly the older Hispanic population.
PMID- 27485159
TI - Serum cell death biomarker mirrors liver cancer regression after transarterial
chemoembolisation.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) represents an increasing health
problem with limited therapeutic options. In patients with intermediate disease
stage, transarterial chemoembolisation (TACE) is widely applied. Treatment
response is routinely assessed by imaging techniques according to the
international response evaluation criteria in solid tumours (RECIST), which
consider tumour regression or additionally tumour necrosis (modified RECIST).
Evaluation of treatment response, however, by these methods is time- and cost
intensive and usually performed at earliest several months following TACE. AIM:
To investigate the suitability of novel non-invasive cell death biomarkers for an
earlier prediction of TACE response. METHODS: We analysed activation of pro
apoptotic caspases and the proteolytic cleavage of the caspase substrate CK-18 in
liver tissues and sera from HCC patients by immunohistochemistry, a luminometric
substrate assay and ELISA. RESULTS: Both caspase activity and caspase-cleaved CK
18 fragments were elevated in HCC patients compared to healthy controls. CK-18
serum levels significantly increased during the first 3 days and peaked at day
two following TACE. Interestingly, we found significant differences in CK-18
levels between patients with and without tumour regression. Detection of CK-18
fragments revealed a promising performance for the early prediction of TACE
response with an area under the curve value of 0.76. CONCLUSIONS: Caspase-cleaved
CK-18 levels mirror liver cancer regression and allow an earlier prediction of
TACE response. The concordance with mRECIST suggests that the detection of CK-18
levels immediately after TACE might be used as a short-term decision guide to
continue or change HCC therapy.
PMID- 27485160
TI - Optimal Device Independent Quantum Key Distribution.
AB - We consider an optimal quantum key distribution setup based on minimal number of
measurement bases with binary yields used by parties against an eavesdropper
limited only by the no-signaling principle. We note that in general, the maximal
key rate can be achieved by determining the optimal tradeoff between measurements
that attain the maximal Bell violation and those that maximise the bit
correlation between the parties. We show that higher correlation between shared
raw keys at the expense of maximal Bell violation provide for better key rates
for low channel disturbance.
PMID- 27485161
TI - More than meets the eye: Emergent properties of transcription factors networks in
Arabidopsis.
AB - Uncovering and mathematically modeling Transcription Factor Networks (TFNs) are
the first steps in engineering plants with traits that are better equipped to
respond to changing environments. Although several plant TFNs are well known, the
framework for systematically modeling complex characteristics such as switch-like
behavior, oscillations, and homeostasis that emerge from them remain elusive.
This review highlights literature that provides, in part, experimental and
computational techniques for characterizing TFNs. This review also outlines
methodologies that have been used to mathematically model the dynamic
characteristics of TFNs. We present several examples of TFNs in plants that are
involved in developmental and stress response. In several cases, advanced
algorithms capture or quantify emergent properties that serve as the basis for
robustness and adaptability in plant responses. Increasing the use of
mathematical approaches will shed new light on these regulatory properties that
control plant growth and development, leading to mathematical models that predict
plant behavior. This article is part of a Special Issue entitled: Plant Gene
Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan
Springer.
PMID- 27485162
TI - Early suppression effect in human primary visual cortex during Kanizsa illusion
processing: A magnetoencephalographic evidence.
AB - Detection of illusory contours (ICs) such as Kanizsa figures is known to depend
primarily upon the lateral occipital complex. Yet there is no universal agreement
on the role of the primary visual cortex in this process; some existing evidence
hints that an early stage of the visual response in V1 may involve relative
suppression to Kanizsa figures compared with controls. Iso-oriented luminance
borders, which are responsible for Kanizsa illusion, may evoke surround
suppression in V1 and adjacent areas leading to the reduction in the initial
response to Kanizsa figures. We attempted to test the existence, as well as to
find localization and timing of the early suppression effect produced by Kanizsa
figures in adult nonclinical human participants. We used two sizes of visual
stimuli (4.5 and 9.0 degrees ) in order to probe the effect at two different
levels of eccentricity; the stimuli were presented centrally in passive viewing
conditions. We recorded magnetoencephalogram, which is more sensitive than
electroencephalogram to activity originating from V1 and V2 areas. We restricted
our analysis to the medial occipital area and the occipital pole, and to a 40-120
ms time window after the stimulus onset. By applying threshold-free cluster
enhancement technique in combination with permutation statistics, we were able to
detect the inverted IC effect-a relative suppression of the response to the
Kanizsa figures compared with the control stimuli. The current finding is highly
compatible with the explanation involving surround suppression evoked by iso
oriented collinear borders. The effect may be related to the principle of sparse
coding, according to which V1 suppresses representations of inner parts of
collinear assemblies as being informationally redundant. Such a mechanism is
likely to be an important preliminary step preceding object contour detection.
PMID- 27485163
TI - Branched Arylalkenes from Cinnamates: Selectivity Inversion in Heck Reactions by
Carboxylates as Deciduous Directing Groups.
AB - A decarboxylative Mizoroki-Heck coupling of aryl halides with cinnamic acids has
been developed in which the carboxylate group directs the arylation into its beta
position before being tracelessly removed through protodecarboxylation. In the
presence of a copper/palladium catalyst, both electron-rich and electron
deficient aryl bromides and chlorides bearing numerous functionalities were
successfully coupled with broadly available cinnamates, with selective formation
of 1,1-disubstituted alkenes. This reaction concept, in which the carboxylate
acts as a deciduous directing group, ideally complements traditional 1,2
selective Heck reactions of styrenes.
PMID- 27485164
TI - Acquired cold urticaria: Clinical features, particular phenotypes, and disease
course in a tertiary care center cohort.
AB - BACKGROUND: Data about special phenotypes, natural course, and prognostic
variables of patients with acquired cold urticaria (ACU) are scarce. OBJECTIVES:
We sought to describe the clinical features and disease course of patients with
ACU, with special attention paid to particular phenotypes, and to examine
possible parameters that could predict the evolution of the disease. METHODS:
This study was a retrospective chart review of 74 patients with ACU who visited a
tertiary referral center of urticaria between 2005 and 2015. RESULTS: Fourteen
patients (18.9%) presented with life-threatening reactions after cold exposure,
and 21 (28.4%) showed negative results after cold stimulation tests (classified
as atypical ACU). Nineteen patients (25.7%) achieved complete symptoms resolution
at the end of the surveillance period and had no subsequent recurrences. Higher
rates of atypical ACU along with a lower likelihood of achieving complete symptom
resolution was observed in patients who had an onset of symptoms during childhood
(P < .05). In patients with atypical ACU, shorter disease duration and lower
doses of antihistamines required for achieving disease control were detected (P <
.05). Age at disease onset, symptom severity, and cold urticaria threshold values
were found to be related to disease evolution (P < .05). LIMITATIONS: This study
was limited by its retrospective nature. CONCLUSIONS: The knowledge of the
clinical predictors of the disease evolution along with the clinical features of
ACU phenotypes would allow for the establishment of an early and proper
therapeutic strategy.
PMID- 27485165
TI - MicroRNA-101 inhibits the proliferation and invasion of bladder cancer cells via
targeting c-FOS.
AB - MicroRNAs (miRs) have important roles in the parthenogenesis of malignancies.
While it has been suggested that deregulation of miR-101 is involved in bladder
cancer, the underlying mechanisms have remained largely elusive. The present
study aimed to investigate the roles of miR-101 in the regulation of bladder
cancer cell proliferation and invasion. Reverse-transcription quantitative
polymerase chain reaction analysis revealed that the expression of miR-101 was
significantly reduced in the HT-1376, BIU87, T24 and 5637 several human bladder
cancer cell lines compared to that in the SV-HUC-1 normal bladder epithelial cell
line. Furthermore, a Targetscan search and a luciferase assay were used to
identify c-FOS as a novel target of miR-101, and western blot analysis indicated
that the protein expression of c-FOS was shown to be negatively regulated by miR
101 in bladder cancer T24 cells; however, c-FOS mRNA expression was not affected.
In addition, plasmid-mediated overexpression of miR-101 and small hairpin RNA
mediated inhibition of c-FOS significantly inhibited the proliferation and
invasive capacity of T24 cells, as indicated by an MTT and a Transwell assay,
respectively. However, plasmid-mediated overexpression of c-FOS reversed the
inhibitory effects of miR-101 overexpression on T24-cell proliferation and
invasion. In conclusion, the present study demonstrated that miR-101 inhibits the
proliferation and invasion of bladder cancer cells, at least partly via targeting
c-FOS, suggesting that miR-101/c-FOS signaling may represent a potential
therapeutic target for bladder cancer.
PMID- 27485166
TI - Erratum: Pubertal development in healthy children is mirrored by DNA methylation
patterns in peripheral blood.
PMID- 27485167
TI - Pathology reporting of malignant pleural mesothelioma first diagnosis: A
population-based approach.
AB - Accurate pathologic diagnosis and reporting in malignant pleural mesothelioma are
essential for clinical care, and cancer registration. Practical guidelines for
pathologists are provided in publications and textbooks but it is unclear how
these recommendations are applied in routine practice. We investigated the
characteristics of pathology reports, and the extent to which they meet guideline
standards. We reviewed 819 pathology reports relating to a first diagnosis of
malignant pleural mesothelioma. Data sources were a regional section of the
Italian network of the Mesothelioma Registry (2001-2014) and a pathology archive
(1990-2000). We evaluated tumor characteristics, the diagnosis field including
terminology and immunohistochemistry (IHC) workup, and report completeness (the
proportion of items recorded). We investigated also two IHC panels identified by
the most used markers in current practical guidelines, one best suited for
epithelioid mesotheliomas (combinations of at least 2 positive and at least 2
negative mesothelioma markers) and the other best suited for sarcomatoid
mesotheliomas (positive mesothelioma markers plus cytokeratins). Reports (753
histology, 66 cytology, IHC-confirmed 86%) were 74% complete and always
narrative. Missing data were related to clinical history (76%), tumor laterality
(61%), specimen size (38%), and histological subtype (23%). The proportion of
cases with IHC was higher for epithelioid (90%) than sarcomatoid mesothelioma
(87%). Compliance to IHC recommendations was higher for epithelioid (59%) than
sarcomatoid mesothelioma (11%). The mean number of stains was significantly
higher for sarcomatoid than epithelioid mesothelioma (p<0.000; Kruskal-Wallis
test). Our findings show that although guidelines are designed to improve actual
reporting practices, there is ample room for improvement in their application to
standardize the diagnosis of mesothelioma. Synoptic pathology reporting needs to
be implemented to better utilize pathology information.
PMID- 27485168
TI - Charles Bonnet syndrome successfully treated with levetiracetam.
PMID- 27485169
TI - Extensive bilateral striopallidodentate calcinosis: a 50 years history of
hypoparathyroidism presenting like a parkinsonian syndrome.
PMID- 27485170
TI - Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a
cluster of severe Guillain-Barre syndrome.
AB - Few regional and seasonal Guillain-Barre syndrome (GBS) clusters have been
reported so far. It is unknown whether patients suffering from sporadic GBS
differ from GBS clusters with respect to clinical and paraclinical parameters,
HLA association and antibody response to glycosphingolipids and Campylobacter
jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich
area in Germany with 14 of those admitted within a period of 3 months in fall
2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes
DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid
antibodies was carried out. Clinical and paraclinical findings (Cj
seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were
obtained and analyzed. GBS cluster patients were characterized by a more severe
clinical phenotype with more patients requiring mechanical ventilation and higher
frequencies of autoantibodies against sulfatide, GalC and certain ganglioside
epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj
seropositivity tended to be higher within GBS cluster patients (69 %) as compared
to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II
allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS
patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher
frequencies of autoantibodies against glycosphingolipids. HLA class II allele
DQB1*05:01 might contribute to clinical worsening in the cluster patients.
PMID- 27485171
TI - Cortical thinning in drug-naive Parkinson's disease patients with depression.
AB - To shed more light on the contribution of brain structural changes to PD-related
depressive symptoms, this study conducted cortical thickness analysis in drug
naive PD patients with and without depression. We recruited 27 PD patients with
depression (PD-Dep), 29 PD patients without depression (PD-NDep), and 56 normal
controls. T1 weighted magnetic resonance imaging and surface-based morphometric
analyses were performed to examine morphometric abnormalities in PD patients and
their relationship to depression. We found decreased thickness in the left
prefrontal cortex in PD-Dep group compared with PD-NDep group. No significant
difference was found between PD patients and controls. In addition, we found
there is a trend of inverse correlation between the structural changes and the
score of depressive symptom in depressed PD patients. This study demonstrates
that cortical thinning in prefrontal area in drug-naive PD patients with
depression and highlights the critical role of prefrontal region in the
depression associated with PD.
PMID- 27485173
TI - The influence of pi-conjugation on competitive pathways: charge transfer or
electron transfer in new D-pi-A and D-pi-Si-pi-A dyads.
AB - In order to elucidate the influence of pi-conjugation on photoinduced electron
transfer (PET) and intramolecular charge transfer processes, donor-pi-acceptor
dyads (D-pi-A (1) and D-pi-Si-pi-A (2)) were newly synthesized. In these dyads,
carbazole and triazine moieties acted as the electron donor and acceptor,
respectively. The fluorescence of dyad 1 red-shifted as the solvent polarity was
increased. The electron charge distribution of the excited state of dyad 1 was
delocalized in the acceptor moiety, forming the charge transfer D(delta+)-pi
A(delta-) dyad in the excited state. In the excited state of dyad 1, the pi
conjugation acted as the linker for charge transfer between the donor and
acceptor moieties. A large dipole moment change (DeltaMU = 45.6 D) between the
ground and excited states was determined using the Lippert-Mataga plot.
Furthermore, the fluorescence of dyad 1 was observed upon two-photon excitation.
In contrast, dyad 2, in which the pi-conjugation is disconnected by a Si-atom in
the linker, displayed weak dual-emission: a short-wavelength emission at around
350 nm arising from the monomeric species and a long-wavelength one assigned to
the emission from an intramolecular exciplex between the donor and acceptor
moieties. The weak emission of dyad 2 indicates that the D(+)-pi-Si-pi-A(-)
species was generated through a PET process in the excited state. The cationic
radical species of the carbazole and the anionic radical species of the triazine,
which show transient absorption (TA) bands at around 780 and 530 nm,
respectively, were characterized using the femtosecond TA method.
PMID- 27485172
TI - Thalamic interictal epileptiform discharges in deep brain stimulated epilepsy
patients.
AB - The relationships between interictal epileptiform discharges (IEDs) in the
anterior (ANT) and dorsomedial nuclei (DMNT) of the thalamus and electro-clinical
parameters in pharmacoresistant focal epilepsy patients receiving intrathalamic
electrodes for deep brain stimulation (DBS) were investigated. Thalamus-localized
IEDs (LIEDs) and surface EEG (sEEG)-IEDs were evaluated in eight patients who
underwent ANT-DBS. Occurrence and frequency of ANT- and DMNT-LIEDs and pre
operative sEEG-IEDs were examined with respect to seizure onset location and
seizure outcome following ANT-DBS. LIEDs were identified in all eight patients,
in the ANT, DMNT, or both. ANT-LIEDs were observed in all patients with an
unequivocal temporal seizure onset zone. The ANT-LIED frequency correlated with
pre-surgical sEEG-IED frequency (rho = 0.76, p = 0.033) and predicted ANT-DBS
responsiveness (T = -2.6; p = 0.0428). Of the five patients with bilateral sEEG
IEDs, all had ANT-LIEDs, but only one patient had DMNT-LIEDs. All patients with
no or unilateral sEEG-IEDs had DMNT-LIEDs. Observation of LIEDS in the ANT and
DMNT supports the hypothesis that these nuclei are involved in propagation of
focal epileptic activity. Their correspondence with differing electro-clinical
features suggests that these nuclei are functionally distinguishable nodes within
the epileptic networks of individual patients.
PMID- 27485174
TI - Incidence, risk factors and outcomes of acute kidney injury (AKI) in patients
with acute-on-chronic liver failure (ACLF) of underlying cirrhosis.
AB - BACKGROUND AND AIMS: Acute kidney injury (AKI) is a life-threatening complication
in patients with acute-on-chronic liver failure (ACLF) of underlying cirrhosis.
However, the characteristics of AKI in these patients have not been clarified.
Our aim was to determine the incidence and risk factors of AKI and the
association between AKI severity and 180-day transplant-free survival. METHODS:
We performed a retrospective cohort analysis of patients with ACLF of underlying
cirrhosis in a single center from January 2009 through December 2014. AKI was
defined by the criteria proposed by International Club of Ascites (ICA). The
incidence and risk factors of AKI development and its relationship to 180-day
transplant-free survival rates were evaluated. RESULTS: Of 1032 patients with
ACLF of underlying cirrhosis, 121 (11.72 %) had AKI at admission, and 319 (30.9
%) developed AKI during hospitalization. We established a logistic regression
model including four independent factors with AKI development: MELD score [odds
ratio (OR), 1.1; 95 % confidence interval (CI), 1.07-1.14], presence of ascites
(OR, 3.80; 95 % CI, 2.13-6.78), sepsis/infection (OR, 2.25; 95 % CI, 1.66-3.03)
and acute variceal bleed (OR, 1.78; 95 % CI, 1.00-3.19). The area under receiver
operating characteristics of the model in internal and external validations were
0.95 and 0.85, respectively. Patients with mild-A AKI had a higher 180-day
transplant-free survival rate (23.8 %) than patients with mild-B AKI (19.0 %) or
marked AKI (5.9 %) (all p < 0.001). AKI patients with a peak value of sCr <1.5
mg/dl had higher 180-day transplant-free survival rates compared to those with a
peak value of sCr ?1.5 mg/dl (23.8 % vs. 14.7 %, p < 0.001). CONCLUSIONS: We
developed a clinical risk model for predicting development of AKI with great
accuracy. Combining the ICA-AKI criteria and the peak value of sCr with 1.5 mg/dl
provides a good prognostic method for patients with ACLF of underlying cirrhosis.
PMID- 27485176
TI - Mcm10: The glue at replication forks.
PMID- 27485177
TI - Inter-disciplinarity in sport sciences: The neuroscience example.
AB - Sport science is a relatively recent domain of research born from the
interactions of different disciplines related to sport. According to the European
College of sport science ( http://sport-science.org ): "scientific excellence in
sport science is based on disciplinary competence embedded in the understanding
that its essence lies in its multi- and interdisciplinary character". In this
respect, the scientific domain of neuroscience has been developed within such a
framework. Influenced by the apparent homogeneity of this scientific domain, the
present paper reviews three important research topics in sport from a
neuroscientific perspective. These topics concern the relationship between mind
and motor action, the effects of cognition on motor performance, and the study of
certain mental states (such as the "flow" effect, see below) and motor control
issues to understand, for example, the neural substrates of the vertical squat
jump. Based on the few extensive examples shown in this review, we argue that by
adopting an interdisciplinary paradigm, sport science can emulate neuroscience in
becoming a mono-discipline.
PMID- 27485175
TI - Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer.
AB - The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is
controversial and there are currently no reliable factors allowing for individual
selection of patients with high risk of relapse for such therapy. We searched for
microRNA-based signature with prognostic significance in this group. We assessed
by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage
pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared
between two groups of patients: 40 and 45 patients who did and did not develop
distant metastases after resection, respectively. Additionally, miRNA expression
was compared between CC and normal colon mucosa samples and between the mismatch
repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR
939 was significantly correlated with shorter distant metastasis-free survival
(DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature
of five miRNAs (miR-1296, miR-135b, miR-539, miR-572 and miR-185) was found to be
prognostic [p = 1.28E-07, HR 8.4 (95 % CI: 3.81-18.52)] for DMFS and cross
validated in a leave-one-out analysis, with the sensitivity and specificity of 74
and 78 %, respectively. The expression of miR-592 was significantly associated
with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs
were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR
423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may
be predictive for the risk of distant relapse in early stage CC and confirmed
previously reported association between miR-592 expression and MMR status.
PMID- 27485178
TI - Removal of oxytetracycline and determining its biosorption properties on aerobic
granular sludge.
AB - This study investigates biosorption of Oxytetracycline, a broad-spectrum
antibiotic, using aerobic granular sludge as an adsorbent in aqueous solutions. A
sequencing batch reactor fed by a synthetic wastewater was operated to create
aerobic granular sludge. Primarily, the pore structure and surface area of
granular sludge, the chemical structure and the molecular sizes of the
pharmaceutical, operating conditions, such as pH, stirring rate, initial
concentration of Oxytetracycline, during adsorption process was verified.
Subsequently, thermodynamic and kinetic aspects of the adsorption were examined
and adsorption isotherm studies were carried out. It was shown that the aerobic
granular sludge was a good alternative for biosorption of this pharmaceutical.
The pharmaceutical was adsorbed better at pH values of 6-8. The adsorption
efficiency increased with rising ionic strength. Also, it was seen that the
adsorption process was an exothermic process in terms of thermodynamics. The
adsorption can be well explained by Langmuir isotherm model.
PMID- 27485179
TI - Arsenate Accumulation, Distribution, and Toxicity Associated with Titanium
Dioxide Nanoparticles in Daphnia magna.
AB - Titanium dioxide nanoparticles (nano-TiO2) are widely used in consumer products.
Nano-TiO2 dispersion could, however, interact with metals and modify their
behavior and bioavailability in aquatic environments. In this study, we
characterized and examined arsenate (As(V)) accumulation, distribution, and
toxicity in Daphnia magna in the presence of nano-TiO2. Nano-TiO2 acts as a
positive carrier, significantly facilitating D. magna's ability to uptake As(V).
As nano-TiO2 concentrations increased from 2 to 20 mg-Ti/L, total As increased by
a factor of 2.3 to 9.8 compared to the uptake from the dissolved phase. This is
also supported by significant correlations between arsenic (As) and titanium (Ti)
signal intensities at concentrations of 2.0 mg-Ti/L nano-TiO2 (R = 0.676, P <
0.01) and 20.0 mg-Ti/L nano-TiO2 (R = 0.776, P < 0.01), as determined by LA-ICP
MS. Even though As accumulation increased with increasing nano-TiO2
concentrations in D. magna, As(V) toxicity associated with nano-TiO2 exhibited a
dual effect. Compared to the control, the increased As was mainly distributed in
BDM (biologically detoxified metal), but Ti was mainly distributed in MSF (metal
sensitive fractions) with increasing nano-TiO2 levels. Differences in subcellular
distribution demonstrated that adsorbed As(V) carried by nano-TiO2 could
dissociate itself and be transported separately, which results in increased
toxicity at higher nano-TiO2 concentrations. Decreased As(V) toxicity associated
with lower nano-TiO2 concentrations results from unaffected As levels in MSFs
(when compared to the control), where several As components continued to be
adsorbed by nano-TiO2. Therefore, more attention should be paid to the potential
influence of nano-TiO2 on bioavailability and toxicity of cocontaminants.
PMID- 27485180
TI - miR-128 promoted adipogenic differentiation and inhibited osteogenic
differentiation of human mesenchymal stem cells by suppression of VEGF pathway.
AB - CONTEXT: MicroRNA-128 (miR-128), a brain-enriched microRNA, has been reported to
participate in the regulation of cell differentiation, but its potential roles in
adipogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs)
have not been addressed. OBJECTIVE: The study was conducted to investigate the
effects and mechanism of miR-128 on adipogenic and osteogenic differentiation of
hMSCs. MATERIALS AND METHODS: Morphology of hMSCs, lipid droplets and calcium
nodules were observed and photographed by LSM microscopy. Expression of
CCAAT/enhancer binding protein-alpha (C/EBPalpha), peroxisome proliferator
activated receptor-gamma (PPARgamma), miR-128, vascular endothelial growth factor
(VEGF), osteocalcin (OCN) and Runt-related transcription factor 2 (RUNX2) was
determined by RNA preparation and reverse transcription polymerase chain reaction
(RT-PCR), protein expression of VEGF was analyzed by Western blot. RESULTS: It
was suggested that miR-128 expression showed a 4.56-fold induction by adipogenic
treatment and a 58.8% reduction by osteogenic treatment. Over-expression of miR
128, promoted adipogenic differentiation while inhibited osteogenic
differentiation. In contrast, adipocyte formation was inhibited and osteogenesis
was enhanced in cells slicing miR-128. Furthermore, over-expression of miR-128
down-regulated VEGF expression in adipogenically and osteogenically
differentiated cells. We further identified VEGF as a key regulator in miR-128
induced adipogenic and osteogenic differentiation. Following knockdown of VEGF,
the effects of over-expression of miR-128 on adipogenic and osteogenic
differentiation of hMSCs were limited. CONCLUSION: It was indicated that miR-128
could regulate adipogenic and osteogenic differentiation of hMSCs significantly
through the suppression of VEGF pathway.
PMID- 27485182
TI - Human gut microbiota plays a role in the metabolism of drugs.
AB - BACKGROUND AND AIMS: The gut microbiome, an aggregate genome of trillions of
microorganisms residing in the human gastrointestinal tract, is now known to play
a critical role in human health and predisposition to disease. It is also
involved in the biotransformation of xenobiotics and several recent studies have
shown that the gut microbiota can affect the pharmacokinetics of orally taken
drugs with implications for their oral bioavailability. METHODS: Review of
Pubmed, Web of Science and Science Direct databases for the years 1957-2016.
RESULTS AND CONCLUSIONS: Recent studies make it clear that the human gut
microbiota can play a major role in the metabolism of xenobiotics and, the
stability and oral bioavailability of drugs. Over the past 50 years, more than 30
drugs have been identified as a substrate for intestinal bacteria. Questions
concerning the impact of the gut microbiota on drug metabolism, remain unanswered
or only partially answered, namely (i) what are the molecular mechanisms and
which bacterial species are involved? (ii) What is the impact of host genotype
and environmental factors on the composition and function of the gut microbiota,
(iii) To what extent is the composition of the intestinal microbiome stable,
transmissible, and resilient to perturbation? (iv) Has past exposure to a given
drug any impact on future microbial response, and, if so, for how long? Answering
such questions should be an integral part of pharmaceutical research and
personalised health care.
PMID- 27485181
TI - Executive function in children with prenatal cocaine exposure (12-15years).
AB - PURPOSE: Prenatal exposure to cocaine (PCE) may alter areas of the brain dense
with monoamine receptors such as the prefrontal cortex and negatively affect
cognitive processes implicated in executive function (EF). This study
investigated the effects of PCE on EF at 12 and 15years. METHODS: EF was examined
in 189 PCE and 183 non-cocaine exposed (NCE) children who were primarily African
American and of low socioeconomic status. Caregivers rated their child on the
Behavior Rating Inventory of Executive Function (BRIEF) at ages 12 and 15. The
BRIEF includes two summary scales and eight subscales: Behavioral Regulation
Index (BRI) (Inhibit, Shift, and Emotion) and Metacognition Index (MI) (Monitor,
Working Memory, Plan/Organize, Organization of Materials and Task Completion).
Two additional measures were included at age 15 (BRIEF Self-Report and the CANTAB
Stockings of Cambridge (SOC)). RESULTS: Girls with PCE were perceived by
caregivers to have more behavioral regulation problems at age 12 (p<0.005) and
more metacognitive problems at age 12 (p<0.003) than NCE females, but there was
no association for males. PCE girls improved in behavioral regulation (p<0.05)
and metacognition (p<0.04) from 12 to 15years compared to NCE girls based on
caregiver report. By self-report PCE was associated with problems of inhibition
(p<0.006). Girls with PCE performed more poorly on number of moves to complete
the SOC, requiring planning and problem solving, than NCE girls. CONCLUSION:
Prenatally cocaine exposed girls were perceived by caregivers as having problems
of behavioral regulation, and by self-report, inhibitory control problems. Girls
with PCE also performed more poorly on a task of planning and problem solving at
age 15 which corresponded to caregiver report at age 12. Early assessment and
remediation of these weaknesses in girls may improve school performance and
behavior associated with poor EF.
PMID- 27485183
TI - The impact of cardiovascular drugs on the efficacy of local anesthesia in
dentistry.
AB - BACKGROUND AND AIM: Drugs used chronically by patients with diseases of the
cardiovascular system (group C of the ATC classification) may act on adrenergic
receptors and/or certain ion channels, which gives them the potential to interact
with the action of local dental anesthetics. The aim of the study was to
investigate the effect of systemically administered chronic cardiovascular
medication (oral route) on the efficacy of intraoral local anesthesia in patients
with diseases of the cardiovascular system. PATIENTS AND METHODS: This was a
prospective cohort study which analyzed the efficacy of local terminal anesthesia
(onset of anesthesia, duration anesthetized area) in the upper jaw of 70
patients: 40 patients on medication for cardiovascular system disorders and 30
patients who were not using these drugs (the control group). The following
cardiovascular drugs were used: beta blockers, angiotensin converting enzyme
inhibitors, calcium channel blockers, vasodilatators, diuretics, angiotensin
receptor blockers, antiarrhythmics, statins and alfa blockers. RESULTS: The onset
of anesthesia on the vestibular side was faster in those taking cardiovascular
drugs (40.50+/-19.87 s) than the control patients (58.93+/-31.07 s; P = 0.004)
and duration of anesthesia on this side was shorter. Although the difference was
not significant, it was evident that on vestibular and palatal side the
anesthetized area was more rapidly reduced in the patients taking cardiovascular
drugs. The duration of cardiovascular therapy also had a significant impact on
the anesthetized area. CONCLUSION: Drugs acting on cardiovascular system may
influence the effect of local anesthetics used in dentistry, possibly through
interaction with autonomic receptors and ion channels.
PMID- 27485184
TI - Significant phenotype variability of congenital central hypoventilation syndrome
in a family with polyalanine expansion mutation of the PHOX2B gene.
AB - BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare genetic
disorder resulting from mutations in the PHOX2B gene located on chromosome
4p12.3, characterized by hypoventilation secondary to missing responses to both
hypercapnia and hypoxia. CASE REPORT: Proband. A girl, hospitalised 5 times for
respiratory failure from 6 weeks old, presented at 4 years of age severe cyanosis
related to pneumonia. Tracheostomy was done, and she was discharged home using a
portable positive pressure ventilator during sleep. Proband's father: The father
was retrospectively found out to suffer from severe headache and excessive
daytime sleepiness. Molecular genetic evaluation of PHOX2B gene was performed and
casual polyalanine repeat expansion mutation c.741_755dup15 in exon 3 was found
both in proband and her father in heterozygous form. The proband's grandmother
died of respiratory failure after administration of benzodiazepine at the age of
fifty years. Considering the grandmother's history, she is highly suspected of
having had CCHS as well. CONCLUSION: Repeated respiratory failure of girl was
explained by PHOX2B mutation and Ondina curse. Proband's father has incompletely
penetrated PHOX2B heterozygous mutation as well and proband's grandmother died
probably from the consequences of drug interaction with PHOX2B mutated background
as well. Both daughter and father currently require overnight mechanical
ventilatory support. Although most PHOX2B mutations occur de novo, our case is a
rare three generation family affected by autosomal dominant inheritance with
incomplete penetrance manifested as the late-form of CCHS and proven PHOX2B
mutation in two generations.
PMID- 27485185
TI - SPECT/CT imaging in breast cancer - current status and challenges.
AB - BACKGROUND: The increasing incidence of breast cancer worldwide raises the
importance of improving imaging techniques for disease stratification after early
lesion detection. SPECT/CT imaging is now widely available but its diagnostic
potential is not fully utilized for more specific purposes including breast
cancer patient stratification. METHODS AND RESULTS: A Pubmed search for both
original and review articles related to the value of SPECT/CT in breast cancer
patients and comparison to other diagnostic methods. 62 articles were found using
the key words SPECT/CT, Fusion Image and Breast Cancer. Development of a new
generation of SPECT/CT systems and their introduction into practice has changed
the old diagnostic algorithm. The increasing importance of SPECT/CT in the
detection of bone metastases is confirmed. The diagnostic accuracy of new
SPECT/CT instruments in the diagnostics of bone metastases is nearly comparable
to PET/CT scans. SPECT/CT is more widely available and costs less than PET. It is
able not only to identify a sentinel lymph nodes in atypical localizations but
also to detect sentinel lymph nodes non visualized on previous planar scans.
SPECT/CT offers precise anatomic localization of sentinel lymph nodes, thereby
facilitating surgery. Knowledge of precise sentinel lymph node localization can
also be applied in radiotherapy. CONCLUSIONS: The role of hybrid SPECT/CT imaging
in breast cancer patients is changing. It is a powerful modality for skeletal and
nodal staging in breast cancer patients with important impact on therapy.
PMID- 27485186
TI - Requirement of TLR4 signaling for the induction of a Th1 immune response elicited
by oligomannose-coated liposomes.
AB - We have previously demonstrated that administration of oligomannose-coated
liposomes (OMLs), in which an antigen is encased, induce antigen-specific Th1
immune responses and CTLs. In the present study, we showed that TLR4 signaling is
required for the induction of specific immune responses following OML
administration. In C3H/HeJ mice, which express a dysfunctional TLR4, the antigen
specific Th1 immune response could not be elicited following intraperitoneal
administration of OVA-encased OMLs (OML/OVA). However, OML uptake by peritoneal
cells, the subsequent production of IL-12 and the upregulation of co-stimulatory
molecules and MHC class II on the cells in response to OML uptake occurred in
C3H/HeJ mice to the same extent as in wild type C3H/HeN mice. In addition,
peritoneal phagocytic cells from TLR4(-/-) mice that ingest OML/OVA can activate
CD4(+) T cells from OT-II mice. On the other hand, the number of OML-ingesting
peritoneal cells that migrated into mesenteric lymph nodes in C3H/HeJ mice was
significantly less than that in C3H/HeN mice. Therefore, the chemotactic
capability of OML-ingesting peritoneal phagocytes to the draining lymph nodes
rather than the activation and maturation of the cells in response to OML uptake
is impaired by lack of TLR4 signaling, and disorder of the Th1 immune response
elicited by OMLs in mice, which lack TLR4 signaling, is due to the impairment of
cell migration following OML uptake.
PMID- 27485187
TI - Regulation of B cell functions by Toll-like receptors and complement.
AB - B cell functions triggered by the clonally-rearranged antigen-specific B cell
receptor (BCR) are regulated by several germ-line encoded receptors - including
Toll-like receptors (TLRs) and complement receptors (CRs). Simultaneous or
sequential engagement of these structures expressed either on the cell membrane
or intracellularly, may fundamentally alter and fine tune activation, antibody
and cytokine production of B cells. Here we review the expression and function of
TLRs and various C3 fragment binding CRs on B cells, emphasizing their role in
different human B cell subsets under physiological and pathological conditions.
Studies underlining the importance of the crosstalk between TLRs and CRs in
regulating B cell functions are also highlighted.
PMID- 27485189
TI - Erratum to: Ethnic/Racial Disparities in the Fetal Growth Outcomes of Ecuadorian
Newborns.
PMID- 27485188
TI - Residential Environment for Outdoor Play Among Children in Latino Farmworker
Families.
AB - Child health and development benefit from physical activity. This analysis
describes the residential play environment for children aged 2-4 years in
farmworker families, their parent-reported levels of play and media time, and the
association of residential environment with play and media time. Mothers with a
child aged 2-4 years in farmworker families (n = 248) completed interviews over 2
years. Outcome measures were daily outdoor play time and media time. Measures of
the residential environment included physical and social components. The mean
min/day for outdoor play was 81.8 (SD 57.3) at baseline, 111.4 (SD 90.1) at year
1 follow-up, and 103.6 (SD 76.2) at year 2 follow-up. The mean media min/day at
baseline was 83.8 (SD 64.3), 93.7 (SD 80.3) min/day at year 1 follow-up, and 59.9
min/day (SD (45.6) at year 2 follow-up. One additional person per bedroom was
associated with 6 fewer min/day with media. The addition of each age appropriate
toy was associated with an additional 12.3 min/day of outdoor play. An additional
type of inappropriate media was associated with 6.8 more min/day with media.
These results suggest changes to the residential environment to improve physical
activity among children in Latino farmworker families.
PMID- 27485190
TI - Coulomb Screening and Coherent Phonon in Methylammonium Lead Iodide Perovskites.
AB - Methylammonium lead iodide (CH3NH3PbI3) hybrid perovskite in the tetragonal and
orthorhombic phases have different exciton binding energies and demonstrate
different excitation kinetics. Here, we explore the role that crystal structure
plays in the kinetics via fluence dependent transient absorption spectroscopy. We
observe stronger saturation of the free carrier concentration under high pump
energy density in the orthorhombic phase relative to the tetragonal phase. We
attribute this phenomenon to small dielectric constant, large exciton binding
energy, and weak Coulomb screening, which results in difficult exciton
dissociation under high light intensity in the orthorhombic phase. At higher
excitation intensities, we observe a coherent phonon with an oscillation
frequency of 23.4 cm(-1) at 77 K, whose amplitude tracks the increase of the
first-order lifetime.
PMID- 27485191
TI - Instructive percutaneous coronary intervention to avoid the risk of side branch
occlusion at a lesion with a lotus root appearance: a case report.
AB - BACKGROUND: A lotus root appearance is a rare entity, and there is little
opportunity to perform coronary intervention for this kind of lesion. Because of
its peculiar anatomical characteristics, one of the problems regarding
percutaneous coronary intervention (PCI) for these lesions is related to the
involvement of branch vessels. CASE PRESENTATION: We encountered a case of PCI
for a stenotic lesion with a lotus root appearance in the mid-portion of the
right coronary artery (RCA). To avoid the risk of right ventricular (RV) branch
occlusion due to stent deployment in the main RCA, we re-crossed the third
guidewire into the main RCA via the nearest point to the RV branch ostium through
the communicating vascular lumen. Thereafter, we deployed a drug-eluting stent in
the main RCA crossing over the RV branch, and the ostium of the RV branch
remained intact, as we expected. CONCLUSIONS: This case is the first report in
the world describing the details of how to maintain the patency of the side
branch bifurcating from a lesion with a lotus root appearance under optical
coherence tomography guidance.
PMID- 27485193
TI - Molecular Informatics Going "Fully Online".
PMID- 27485192
TI - Abdomen/pelvis computed tomography in staging of pediatric Hodgkin Lymphoma: is
it always necessary?
AB - The purpose of the study was to determine if abdomen/pelvis computed tomography
(CT) can be safety omitted in the initial staging of a subgroup of children
affected by Hodgkin Lymphoma (HL). Every participating center of A.I.E.O.P
(Associazione Italiana di Ematologia ed Oncologia Pediatrica) sent local staging
reports of 18F-fluorodeoxyglucose positron emission tomography (PET) and
abdominal ultrasound (US) along with digital images of staging abdomen/pelvis CT
to the investigation center where the CT scans were evaluated by an experienced
pediatric radiologist. The local radiologist who performed the US was unaware of
local CT and PET reports (both carried out after US), and the reviewer
radiologist examining the CT images was unaware of local US, PET and CT reports.
A new abdominal staging of 123 patients performed on the basis of local US
report, local PET report, and centralized CT report was then compared to a
simpler staging based on local US and PET. No additional lesion was discovered by
CT in patients with abdomen/pelvis negativity in both US and PET or isolated
spleen positivity in US (or US and PET), and so it seems that in the initial
staging, abdomen/pelvis CT can be safety omitted in about 1/2 to 2/3 of children
diagnosed with HL.
PMID- 27485194
TI - Bilinear Model for the Size-Dependency of the CYP3A4 Inhibitory Activity of
Structurally Diverse Compounds.
AB - A quantitative structure-activity relationship analysis of the inhibitory
activity of structurally diverse compounds on recombinant human CYP3A4 is
presented using a bilinear approach based on our previously developed LinBiExp
model. Using only two main descriptors, molecular size and an indicator variable
for the presence of triazole/imidazole moieties, this approach can account for
close to 65 % of the variability in the inhibitory activity of more than 70
compounds and provides clear evidence that molecular size plays an important, but
nonlinear role. Strongest inhibitory activity is likely to occur for compounds
close to an optimal size, which is roughly that of the well-know CYP3A4-inhibitor
ketoconazole. The activity-limiting role of size was also confirmed on a large
dataset of 3438 compounds (PubChem Bioassay AID 884). This model provides a
simple, intuitive interpretation and can serve as the starting point for more
complex descriptions of the CYP3A4 inhibitory activity.
PMID- 27485195
TI - Pharmacophore Model Refinement for 11beta-Hydroxysteroid Dehydrogenase
Inhibitors: Search for Modulators of Intracellular Glucocorticoid Concentrations.
AB - 11beta-Hydroxysteroid dehydrogenases (11beta-HSD) control the intracellular
concentrations of glucocorticoids: 11beta-HSD1 converts the inactive cortisone to
the active cortisol, and 11beta-HSD2 is responsible for the opposite reaction.
Inhibition of 11beta-HSD1 is beneficial in the treatment of metabolic syndrome,
whereas 11beta-HSD2 inhibition leads to hypertension. Therefore, 11beta-HSD1
inhibitors should be selective over 11beta-HSD2. To support drug discovery and
toxicological studies, we have previously reported pharmacophore models for
11beta-HSD1 and 2 inhibition. These models represent the common chemical features
of 11beta-HSD inhibitors, which were used as virtual screening filter. Since new
inhibitors are constantly discovered, the quality of the pharmacophore models has
to be evaluated in order to maintain a good predictive power. In this study, we
report a systematic evaluation and refinement of our pharmacophore model
collection. We employed our models for virtual screening, especially focusing on
the 11beta-HSD2 inhibition. In total, 42 compounds were biologically evaluated
and among these we discovered 17 11beta-HSD inhibitors that decreased the
residual enzyme activity to 50% or less at the concentration of 20 uM. The
experimental 11beta-HSD1 and 2 readouts from these compounds were used for
further model refinement. Evaluation metrics were applied for a quantitative
comparison of the old and newly generated models which resulted in a set of
improved pharmacophore models offering reliable in silico tools for the
identification of novel and selective 11beta-HSD inhibitors.
PMID- 27485196
TI - Applicability Domain Dependent Predictive Uncertainty in QSAR Regressions.
AB - Predictive models used in decision making, such as QSARs in chemical regulation
or drug discovery, call for evaluated approaches to quantitatively assess
associated uncertainty in predictions. Uncertainty in less reliable predictions
may be captured by locally varying predictive errors. In the current study, model
based bootstrapping was combined with analogy reasoning to generate predictive
distributions varying in magnitude over a model's domain of applicability. A
resampling experiment based on PLS regressions on four QSAR data sets
demonstrated that predictive errors assessed by k nearest neighbour or weighted
PRedicted Error Sum of Squares (PRESS) on samples of external test data or by
internal cross-validation improved the performance of the uncertainty assessment.
Analogy using similarity defined by Euclidean distances, or differences in
standard deviation in perturbed predictions, resulted in better performances than
similarity defined by distance to, or density of, the training data. Locally
assessed predictive distributions had on average at least as good coverage as
Gaussian distribution with variance assessed from the PRESS. An R-code is
provided that evaluates performances of the suggested algorithms to assess
predictive error based on log likelihood scores and empirical coverage graphs,
and which applies these to derive confidence intervals or samples from the
predictive distributions of query compounds.
PMID- 27485197
TI - Application of EMBM to Structure-Based Design of Warheads for Protease
Inhibitors.
AB - Most CADD tools handle non-covalent enzyme inhibitors, despite the growing
interest of the pharma industry in covalent inhibitors. We have recently
introduced an enzyme mechanism-based method, EMBM, as a computational tool for
binding trend analysis and prediction of chemical sites (CS) of reversible
covalent enzyme inhibitors. In the current study we demonstrate the utility of
EMBM to structure-based applications. In this mode, the energy of the enzyme
inhibitor covalent bond is accounted for by the W1 and W2 covalent descriptors we
have developed, whereas the non-covalent interactions between the inhibitor CS
and the enzyme active site can be estimated directly on the 3D structure of the
enzyme-inhibitor complex.
PMID- 27485198
TI - Integrating Computational Modeling and Experimental Assay to Discover New Potent
ACE-Inhibitory Peptides.
AB - Human angiotensin-I-converting enzyme (ACE) is an important target of
antihypertensive therapy, which possesses a bulky, hydrophobic pocket that is
physicochemically compatible with a wide variety of peptide substrates and small
molecule ligands. Rational design of potent ACE inhibitors has long been an
attractive topic in the chemical, biological and medical communities. In the
present study, an integrative protocol is described to optimize and modify
peptides bound with ACE based on their complex three-dimensional structures. The
protocol combines a number of sophisticated computational methods including
molecular dynamics (MD) simulation, quantitative structure-activity relationship
(QSAR), molecular mechanics/Poisson-Boltzmann surface area (MM-PB/SA) and quantum
mechanics/molecular mechanics (QM/MM) to discover new potent ACE-inhibitory
peptides. With this strategy hundreds of potential peptides are generated
virtually, from which several promising candidates are synthesized and assayed in
vitro using a standard Fmoc -protected amino acid solid phase synthesis and
spectrophotometric method, respectively. Six peptides are found to have potency
against ACE, four of which (LVY, VLKP, MLPVY and LKIPLY) show satisfactory
inhibitory capability (pIC50 =5.84, 5.27, 5.40 and 5.57, respectively).
Subsequently, the complex structures of tripeptide LVY and hexapeptide LKIPLY
with ACE are computationally modeled and their binding free energies are
estimated as - 34.2 and - 57.8 kcal/mol, respectively, by using a rigorous QM/MM
scheme. Intensive steric collisions are observed around the C-terminus of peptide
ligands in the bound state. Based upon the findings the C-terminal residues of
the two peptides are modified to small, hydrophobic amino acids Val and Ala,
resulting in mutated peptides LVA and LKIPVA, respectively. Consequently, a
significant improvement in ACE-inhibitory activity is observed for the LKIPVA
mutant (pIC50 increases from 5.57 to 6.07), whereas only a modest activity change
was associated with the LVA mutant (pIC50 decreases from 5.84 to 5.80).
PMID- 27485199
TI - Alkylphosphocholines as Promising Antitumor Agents: Exploring the Role of
Structural Features on the Hemolytic Potential.
AB - Alkylphosphocholines (APC) are promising antitumor agents, which have the
cellular membrane as primary target; however, red blood cell damage limits their
wide therapeutic use. A variety of APC analogs has been synthesized and tested
showing less hemolytic effect than the class prototype, Miltefosine (HePC). In
this work, chemometric methods were applied to a set of 34 APC derivatives to
identify the most relevant structural and molecular features of hemolytic
activity. The APC derivatives were divided into three groups: (i) N
methylpiperidine and N-methylmorpholine derivatives with a long alkyl chain or
flexible cyclopentadecyl rings, displaying a hemolytic rate of 17 %; (ii)
adamantyl and cyclopentadecyl derivatives, showing an average hemolysis of 39 %;
and, N,N,N-trimethylammonium, trans-N,N,N-trimethylcyclohexanamine, and trans
N,N,N-trimethylcyclopentanamine derivatives, whose average hemolysis was 41 %.
The findings suggested that the presence of either bulky cationic head groups, or
rings such as adamantyl and cyclohexyl, primarily increases the hemolysis of
compounds with eleven atoms in the alkyl chain. Moreover, the macrocyclic
cyclopentadecyl seems to be important to the hemolytic potential especially of
compounds with five carbon atoms in the alkyl chain. Regarding linear carbon
chain derivatives with no ring substitution, less bulky cationic head groups seem
to favor hemolysis. Thus, in order to design more potent and less toxic APC
antitumors, the reported structural/molecular patterns should not be included in
their structure.
PMID- 27485200
TI - Prediction of Protein?Protein Interaction Pocket Using L-Shaped PLS Approach and
Its Visualizations by Generative Topographic Mapping.
AB - Protein?protein interaction (PPI) pockets in a host?guest protein system were
predicted using an L-shaped partial least squares (LPLS) method. LPLS is an
extension of standard PLS regression, where, in addition to response vector y and
regressor matrix X, an extra data matrix Z is constructed which summarizes the
background information on X. The regressor matrix X is a similarity matrix of
Tanimoto coefficients of the paired fingerprints of pockets, while the background
information Z constitutes eleven physico-chemical and geometrical parameters for
describing a pocket. The Boolean response vector y specifies whether each pocket
is PPI or non-PPI (indicated by 1 and 0, respectively). Constructing two LPLS
models, we successfully predicted the PPI pockets of two protein clusters.
Clusters 1 and 2 comprised the X-ray crystal structures of protein-peptide
complexes and protein-protein complexes, respectively. From the loading plots
derived from each model, we could speculate the geometrical constraints of the
PPI pockets. These two models are exclusively unique and it was validated by the
cross-prediction simulations. The PPI pockets of cluster 1 were projected onto 2D
maps by generative topographic mapping (GTM) and the molecular lipophilic
potentials (MLP). Among three examples, the MLP distributions were highly similar
because the specimens shared the same p53 guest peptides. Contribution to the
Autumn School of Chemoinformatics in Nara, Japan, November 27-28, 2013.
PMID- 27485201
TI - Modeling the Biodegradability of Chemical Compounds Using the Online CHEmical
Modeling Environment (OCHEM).
AB - Biodegradability describes the capacity of substances to be mineralized by free
living bacteria. It is a crucial property in estimating a compound's long-term
impact on the environment. The ability to reliably predict biodegradability would
reduce the need for laborious experimental testing. However, this endpoint is
difficult to model due to unavailability or inconsistency of experimental data.
Our approach makes use of the Online Chemical Modeling Environment (OCHEM) and
its rich supply of machine learning methods and descriptor sets to build
classification models for ready biodegradability. These models were analyzed to
determine the relationship between characteristic structural properties and
biodegradation activity. The distinguishing feature of the developed models is
their ability to estimate the accuracy of prediction for each individual
compound. The models developed using seven individual descriptor sets were
combined in a consensus model, which provided the highest accuracy. The
identified overrepresented structural fragments can be used by chemists to
improve the biodegradability of new chemical compounds. The consensus model, the
datasets used, and the calculated structural fragments are publicly available at
http://ochem.eu/article/31660.
PMID- 27485202
TI - Effect of evodiamine on the proliferation and apoptosis of A549 human lung cancer
cells.
AB - Evodia rutaecarpa is a plant, which has antitumor activity. Evodiamine is an
alkaloid with antitumor activity present in E. rutaecarpa and has potential to be
developed into a therapeutic antitumor agent. The present study investigated the
effect of evodiamine on the proliferation of A549 human lung cancer cells and the
mechanism underlying these effects. The results indicated that evodiamine
significantly inhibited proliferation, induced apoptosis and the expression of
reactive oxygen species, arrested the cell cycle, regulated the expression of
Survivin, Bcl-2 and Cyclin B1, regulated the activity of caspase-3/8 and
glutathione in tumor cells, and decreased the activity of AKT/nuclear factor
kappaB (NF-kappaB) and Sonic hedgehog/GLI family zinc finger 1 (SHH/GLI1)
signaling pathways in A549 cells. In conclusion, the evodiamine-induced
inhibition of the proliferation of A549 lung cancer cells may be attributable to
its ability to promote oxidative injury in the cells, induce apoptosis, arrest
the cell cycle and regulate the AKT/NF-kappaB and SHH/GLI1 signaling pathways,
subsequently controlling the expression of tumor-associated genes.
PMID- 27485203
TI - Delimitating cryptic species in the Gracilaria domingensis complex
(Gracilariaceae, Rhodophyta) using molecular and morphological data.
AB - Species in the genus Gracilaria that display conspicuously flattened vegetative
morphologies are a taxonomically challenging group of marine benthic red algae.
This is a result of their species richness, morphological similarity, and broad
phenotypic plasticity. Within this group, the Gracilaria domingensis complex is
one of the most common, conspicuous, and morphologically variable species along
the tropical western Atlantic Ocean. Previous research has identified that
members of this complex belong to two distantly related clades. However, despite
this increased phylogentic resolution, species delimitations within each of these
clades remain unclear. Our study assessed the species diversity within this
difficult complex using morphological and molecular data from three genetic
markers (cox1, UPA, and rbcL). We additionally applied six single-marker species
delimitation methods (SDM: ABGD, GMYCs, GMYCm, SPN, bPTP, and PTP) to rbcL, which
were largely in agreement regarding species delimitation. These results, combined
with our analysis of morphology, indicate that the G. domingensis complex
includes seven distinct species, each of which are not all most closely related:
G. cervicornis; a ressurected G. ferox; G. apiculata subsp. apiculata; a new
species, Gracilaria baiana sp. nov.; G. intermedia subsp. intermedia; G.
venezuelensis; and G. domingensis sensu stricto, which includes the later
heterotypic synonym, G. yoneshigueana. Our study demonstrates the value of
multipronged strategies, including the use of both molecular and morphological
approaches, to decipher cryptic species of red algae.
PMID- 27485205
TI - A high-resolution map of the gut microbiota in Atlantic salmon (Salmo salar): A
basis for comparative gut microbial research.
AB - Gut health challenges, possibly related to alterations in gut microbiota, caused
by plant ingredients in the diets, cause losses in Atlantic salmon production. To
investigate the role of the microbiota for gut function and health, detailed
characterization of the gut microbiota is needed. We present the first in-depth
characterization of salmon gut microbiota based on high-throughput sequencing of
the 16S rRNA gene's V1-V2 region. Samples were taken from five intestinal
compartments: digesta from proximal, mid and distal intestine and of mucosa from
mid and distal intestine of 67.3 g salmon kept in seawater (12-14 degrees C) and
fed a commercial diet for 4 weeks. Microbial richness and diversity differed
significantly and were higher in the digesta than the mucosa. In mucosa,
Proteobacteria dominated the microbiota (90%), whereas in digesta both
Proteobacteria (47%) and Firmicutes (38%) showed high abundance. Future studies
of diet and environmental impacts on gut microbiota should therefore
differentiate between effects on mucosa and digesta in the proximal, mid and the
distal intestine. A core microbiota, represented by 22 OTUs, was found in 80% of
the samples. The gut microbiota of Atlantic salmon showed similarities with that
of mammals.
PMID- 27485204
TI - PKM2 dephosphorylation by Cdc25A promotes the Warburg effect and tumorigenesis.
AB - Many types of human tumour cells overexpress the dual-specificity phosphatase
Cdc25A. Cdc25A dephosphorylates cyclin-dependent kinase and regulates the cell
cycle, but other substrates of Cdc25A and their relevant cellular functions have
yet to be identified. We demonstrate here that EGFR activation results in c-Src
mediated Cdc25A phosphorylation at Y59, which interacts with nuclear pyruvate
kinase M2 (PKM2). Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2
dependent beta-catenin transactivation and c-Myc-upregulated expression of the
glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates
itself in a positive feedback loop. Cdc25A-mediated PKM2 dephosphorylation
promotes the Warburg effect, cell proliferation and brain tumorigenesis. In
addition, we identify positive correlations among Cdc25A Y59 phosphorylation,
Cdc25A and PKM2 in human glioblastoma specimens. Furthermore, levels of Cdc25A
Y59 phosphorylation correlate with grades of glioma malignancy and prognosis.
These findings reveal an instrumental function of Cdc25A in controlling cell
metabolism, which is essential for EGFR-promoted tumorigenesis.
PMID- 27485206
TI - Polybrominated diphenylethers (PBDEs) and their hydroxylated metabolites (OH
PBDEs) in female serum from Dalian, China.
AB - Seven polybrominated diphenyl ethers (PBDEs) and eleven hydroxylated PBDEs (OH
PBDEs) were selected to investigate their contamination status in 32 female serum
samples from Dalian, China. These studied PBDEs and OH-PBDEs were found in most
of the serum samples with the concentrations of SigmaPBDEs and SigmaOH-PBDEs
ranging from 1.07 to 38.7ng/g lipid (median: 5.56ng/g lipid) and from 0.011 to
0.436ng/g lipid (median: 0.069ng/g lipid), respectively. More impressively, BDE
47 and OH-BDE-47 were the predominant congeners in female serum, accounting for
52% of SigmaPBDEs and 46% of SigmaOH-PBDEs, respectively. Correspondence analysis
indicated that significant (p<0.05) positive correlations were observed between
BDE-47 and its metabolites such as 6-OH-BDE-47, 3-OH-BDE-47 and 4'-OH-BDE-49. In
addition, the positive significant (p<0.05) correlation was shown between ?PBDEs
and lipid contents but between concentrations of ?PBDEs and ages or BMIs, as well
as for ?OH-PBDEs.
PMID- 27485208
TI - Pituitary response to thyrotropin releasing hormone in children with overweight
and obesity.
AB - Thyroid stimulating hormone (TSH) concentrations in the high normal range are
common in children with overweight and obesity, and associated with increased
cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms
underlying these high TSH concentrations mainly focused on factors promoting
thyrotropin releasing hormone (TRH) production as a cause for high TSH
concentrations. However, it is unknown whether TSH release of the pituitary in
response to TRH is affected in children with overweight and obesity. Here we
describe TSH release of the pituitary in response to exogenous TRH in 73
euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH
concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these
concentrations were positively associated with TSH concentrations 20 minutes
after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area
under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These
results suggest that pituitary TSH release in response to TRH stimulation might
be an important factor contributing to high normal serum TSH concentrations,
which is a regular finding in children with overweight and obesity. The clinical
significance and the intermediate factors contributing to pituitary TSH release
need to be elucidated in future studies.
PMID- 27485209
TI - Tracking tool for frailty: ABCDEF.
AB - The aging population leads to psychological, medical and social reflection for
optimal care of the elderly, especially characterized by a frailty state. The
frailty is the cause of morbi-mortality require screening to anticipate these
complications. The objective was to evaluate the statistical performance and
feasibility of the tool "ABCDEF" to screen frailty defined by Fried's criteria. A
prospective multicenter study including 300 ambulatory elderly consultants was
conducted. ABCDEF appears feasible without major prior training or special
equipment by any doctor or caregiver during an assessment in 98% of consultants.
His sensitivity to detect frailty, is of 75% and specificity of 64%. The frailty
tracking threshold is 3 criteria (6). Its negative predictive value is
interesting because it eliminates the hypothesis of frailty in 91% of cases. This
tracking tool requires, when abnormal, further geriatric assessment. It provides
a standardized and normative approach to describe frailty whose frequency is high
in people older than 80 and whose consequences are major.
PMID- 27485207
TI - Genetic analysis of variation in lifespan using a multiparental advanced
intercross Drosophila mapping population.
AB - BACKGROUND: Considerable natural variation for lifespan exists within human and
animal populations. Genetically dissecting this variation can elucidate the
pathways and genes involved in aging, and help uncover the genetic mechanisms
underlying risk for age-related diseases. Studying aging in model systems is
attractive due to their relatively short lifespan, and the ability to carry out
programmed crosses under environmentally-controlled conditions. Here we
investigate the genetic architecture of lifespan using the Drosophila Synthetic
Population Resource (DSPR), a multiparental advanced intercross mapping
population. RESULTS: We measured lifespan in females from 805 DSPR lines, mapping
five QTL (Quantitative Trait Loci) that each contribute 4-5 % to among-line
lifespan variation in the DSPR. Each of these QTL co-localizes with the position
of at least one QTL mapped in 13 previous studies of lifespan variation in flies.
However, given that these studies implicate >90 % of the genome in the control of
lifespan, this level of overlap is unsurprising. DSPR QTL intervals harbor 11-155
protein-coding genes, and we used RNAseq on samples of young and old flies to
help resolve pathways affecting lifespan, and identify potentially causative loci
present within mapped QTL intervals. Broad age-related patterns of expression
revealed by these data recapitulate results from previous work. For example, we
see an increase in antimicrobial defense gene expression with age, and a decrease
in expression of genes involved in the electron transport chain. Several genes
within QTL intervals are highlighted by our RNAseq data, such as Relish, a
critical immune response gene, that shows increased expression with age, and UQCR
14, a gene involved in mitochondrial electron transport, that has reduced
expression in older flies. CONCLUSIONS: The five QTL we isolate collectively
explain a considerable fraction of the genetic variation for female lifespan in
the DSPR, and implicate modest numbers of genes. In several cases the candidate
loci we highlight reside in biological pathways already implicated in the control
of lifespan variation. Thus, our results provide further evidence that functional
genetics tests targeting these genes will be fruitful, lead to the identification
of natural sequence variants contributing to lifespan variation, and help uncover
the mechanisms of aging.
PMID- 27485210
TI - Highly Efficient Multiphoton-Pumped Frequency-Upconversion Stimulated Blue
Emission with Ultralow Threshold from Highly Extended Ladder-Type Oligo(p
phenylene)s.
AB - A series of highly extended pi-conjugated ladder-type oligo(p-phenylene)s
containing up to 10 phenyl rings with (L)-Ph(n)-NPh (n=7-10) or without
diphenylamino endcaps (L)-Ph(n) (n=7 and 8) were synthesized and investigated for
their multiphoton absorption properties for frequency upconverted blue
ASE/lasing. Extremely large two-photon absorption (2PA) cross-sections and highly
efficient 2PA ASE/lasing with ultralow threshold were achieved. (L)-Ph(10)-NPh
exhibits the highest intrinsic 2PA cross-section of 3643 GM for a blue emissive
organic fluorophore reported so far. The record-high 2PA pumped ASE/lasing
efficiency of 2.06 % was obtained by un-endcapped oligomer, (L)-Ph(8) rather than
that with larger sigma2 , suggesting that a molecule with larger sigma2 is not
guaranteed to exhibit higher eta2 . All of these oligomers exhibit exceptionally
ultralow 2PA pumped ASE/lasing thresholds, among which the lowest 2PA pumped
threshold of circa 0.26 MUJ was achieved by (L)-Ph(10)-NPh.
PMID- 27485211
TI - Low prevalence of dihydro folate reductase (dhfr) and dihydropteroate synthase
(dhps) quadruple and quintuple mutant alleles associated with SP resistance in
Plasmodium vivax isolates of West Bengal, India.
AB - BACKGROUND: Emergence of chloroquine resistant Plasmodium vivax is a serious
obstacle towards malaria control in India. This study elucidates the temporal
pattern of antifolate [sulfadoxine-pyrimethamine (SP)] resistance in P. vivax
infection by means of genetic polymorphisms, especially analysing the single
nucleotide polymorphisms of dihydrofolate reductase (pvdhfr) and dihydropteroate
synthase (pvdhps) gene among the field isolates of urban Kolkata Municipal
Corporation and rural Purulia region of West Bengal, India. METHODS: Blood
samples were collected from 99 microscopically diagnosed P. vivax patients (52
from Kolkata Municipal Corporation and 47 from Purulia). Parasitic DNA was
extracted followed by polymerase chain reaction and sequencing of different
codons of pvdhfr gene (15, 33, 50, 57, 58, 61, 64, 117, and 173 codons) and
pvdhps gene (373, 380, 382, 383, 384, 512, 553, 585, and 601 codons) were
performed to identify the mutations. RESULTS: Prevalence of double mutant dhfr
A15P33N50F57 R 58 T61V64 N 117 I173 allele (53.85 %) was observed in Kolkata
Municipal Corporation (KMC) whereas in Purulia, wild dhfr
A15P33N50F57S58T61V64S117I173 allele was predominated (48.94 %). In pvdhps gene a
significant number of isolates (17.31 %) in KMC contained the double mutant
S373E380S382 G 383 P384K512 G 553 V585M601 allele. pvdhfr and pvdhps combination
haplotype revealed the emergence of quadruple (13.46 %) and quintuple (3.84 %)
mutant allele in KMC, which might result in poor clinical response against
antifolate drugs. CONCLUSION: The study reveals that P. vivax parasites in rural
Purulia may still be susceptible to SP but additional caution should be taken for
treatment of vivax malaria in KMC to limit the blooming of quadruple and
quintuple mutant allele in the remainder of the West Bengal, India.
PMID- 27485212
TI - Acute upregulation of neuronal mitochondrial type-1 cannabinoid receptor and it's
role in metabolic defects and neuronal apoptosis after TBI.
AB - Metabolic defects and neuronal apoptosis initiated by traumatic brain injury
(TBI) contribute to subsequent neurodegeneration. They are all regulated by
mechanisms centered around mitochondrion. Type-1 cannabinoid receptor (CB1) is a
G-protein coupled receptor (GPCR) enriched on neuronal plasma membrane. Recent
evidences point to the substantial presence of CB1 receptors on neuronal
mitochondrial outer membranes (mtCB1) and the activation of mtCB1 influences
aerobic respiration via inhibiting mitochondrial cyclic adenosine monophosphate
(cAMP)/protein kinase A (PKA)/complex I pathway. The expression and role of
neuronal mtCB1 under TBI are unknown. Using TBI models of cultured neurons, wild
type and CB1 knockout mice, we found mtCB1 quickly upregulated after TBI.
Activation of mtCB1 promoted metabolic defects accompanied with ATP shortage but
protected neurons from apoptosis. Selective activation of plasma membrane CB1
showed no effects on neuronal metabolism and apoptosis. Activation of mtCB1
receptors inhibited mitochondrial cAMP/PKA/complex I and resulted in exacerbated
metabolic defects accompanied with a higher ratio of ATP reduction to oxygen
consumption decrease as well as neuronal apoptosis. Further research found the
remarkable accumulation of protein kinase B (AKT) on neuronal mitochondria
following TBI and the activation of mtCB1 upregulated mitochondrial AKT/complex V
activity. Upregulation of mitochondrial AKT/complex V activity showed anti
apoptosis effects and alleviated ATP shortage in metabolic defects. Taken
together, we have identified mtCB1 quickly upregulate after TBI and a dual role
the mtCB1 might play in metabolic defects and neuronal apoptosis initiated by
TBI: the inhibition of mitochondrial cAMP/PKA/complex I aggravates metabolic
defects, energy insufficiency as well as neuronal apoptosis, but the coactivation
of mitochondrial AKT/complex V mitigates energy insufficiency and neuronal
apoptosis.
PMID- 27485213
TI - The impact of identifying carotid plaque on addressing cardiovascular risk in
psoriatic arthritis.
AB - BACKGROUND: Patients with psoriatic arthritis (PsA) are at an increased risk for
cardiovascular (CV) disease. The aim of this study was to identify the frequency
of carotid plaque in asymptomatic patients with psoriatic arthritis at baseline
and follow-up screening, and to assess for the impact of demonstrating plaque on
management of traditional cardiovascular risk factors. METHODS: Eighty-seven PsA
patients underwent carotid duplex ultrasound screening. Repeat carotid duplex
ultrasound was offered to all patients between 12 and 30 months. Preventive
cardiology referrals were generated for all patients through the electronic
health record. Traditional cardiovascular risk factors, medication use, and rates
of utilization of preventive cardiology services were compared between patients
with and without plaque. RESULTS: Carotid plaque was identified in 34/87 (39 %)
of PsA patients. Age and triglyceride levels were predictors of plaque presence.
Patients with plaque trended toward higher rates of smoking and diabetes, and
higher low-density lipoprotein levels. Only 9/87 (10 %) patients completed at
least one visit with preventive cardiology after enrollment despite referral. Low
use of statin (21 %) and antiplatelet (27 %) medication was observed. Rates of
biologic medication use for PsA were higher (75 %) than studies in similar
cohorts of patients with carotid plaque. No association was seen between disease
duration or activity and the presence of carotid plaque. CONCLUSION: Despite
demonstration of high cardiac risk by the presence of carotid plaque,
implementation of preventive cardiovascular services and rates of statin and
antiplatelet use remained low. Age and triglyceride levels were significant
variables in predicting plaque presence. There is no evidence that demonstration
of plaque resulted in further evaluation or changes in treatment regimens to
address heightened cardiovascular risk.
PMID- 27485214
TI - Relative abdominal adiposity is associated with chronic low back pain: a
preliminary explorative study.
AB - BACKGROUND: Although previous research suggests a relationship between chronic
low back pain (cLBP) and adiposity, this relationship is poorly understood. No
research has explored the relationship between abdominal-specific subcutaneous
and visceral adiposity with pain and disability in cLBP individuals. The aim of
this study therefore was to examine the relationship of regional and total body
adiposity to pain and disability in cLBP individuals. METHODS: A preliminary
explorative study design of seventy (n = 70) adult men and women with cLBP was
employed. Anthropometric and adiposity measures were collected, including body
mass index, waist-to-hip ratio, total body adiposity and specific ultrasound
based abdominal adiposity measurements. Self-reported pain and disability were
measured using a Visual Analogue Scale (VAS) and the Oswestry Disability Index
(ODI) questionnaires respectively. Relationships between anthropometric and
adiposity measures with pain and disability were assessed using correlation and
regression analyses. RESULTS: Significant correlations between abdominal to
lumbar adiposity ratio (A-L) variables and the waist-to-hip ratio with self
reported pain were observed. A-L variables were found to predict pain, with 9.1
30.5 % of the variance in pain across the three analysis models explained by
these variables. No relationships between anthropometric or adiposity variables
to self-reported disability were identified. CONCLUSIONS: The findings of this
study indicated that regional distribution of adiposity via the A-L is associated
with cLBP, providing a rationale for future research on adiposity and cLBP.
PMID- 27485215
TI - 10-Year experience regarding the reliability and morbidity of radio guided lymph
node biopsy in penile cancer patients and the associated radiation exposure of
medical staff in this procedure.
AB - BACKGROUND: The guidelines of the European Association of Urologists (EAU), of
the German Society of Nuclear Medicine (DGN), and the European Society for
Medical Oncology (ESMO) recommend sentinel lymph node biopsy (SLNB) for lymph
node staging in penile cancer with non-palpable inguinal lymph nodes as one
diagnostic method. Despite this, the method is neither widely nor regularly
applied in Germany - the same applies to many other countries, which may be due
to insecurity in dealing with open radioactive tracers. This study aims to assess
the reliability and morbidity of this method, as well as the associated
radioactive burden for clinical staff. METHODS: Between 2006 and 2016, 34
patients with an invasive penile carcinoma and inconspicuous inguinal lymph node
status underwent SLNB in 57 groins after application of a radiotracer (Tc-99 m
nanocolloid). We collected the results prospectively. The reliability of the
method was assessed by determining the false-negative rate. In addition, we
evaluated complication rates and determined the radioactive burden for the
clinical staff both pre- and intraoperatively. RESULTS: SLNB was performed in 34
patients with penile cancer with non-palpable inguinal lymph nodes in 57 groins.
In two patients inguinal lymph node metastases were detected by means of SLNB. In
one patient recurrent inguinal lymph node disease was found after negative SLNB
in both groins. Thus, the false negative rate was 3.13 % per patient (1/32
patients) and 3.51 % per groin (2/57 groins). The morbidity rate was 2.94 % per
patient (1/34 patients) and 1.75 % per groin (1/57 groins). Radiation exposure
for the clinical staff during this procedure was low at a maximum of ca. four
MUSV per intervention. CONCLUSIONS: SLNB is a reliable method with low morbidity
that is associated with a low radiation burden for clinical staff. Due to the
enhanced methodological and logistic demands, this intervention should be
performed in specialized centres and in an interdisciplinary approach.
PMID- 27485216
TI - Molecular analysis of myocilin and optineurin genes in Korean primary glaucoma
patients.
AB - To investigate the underlying genetic influences of primary glaucoma in Korea,
molecular analysis was performed in 112 sporadic cases, and results compared with
healthy controls. The myocilin (MYOC) and optineurin (OPTN) genes were directly
sequenced in 112 unrelated patients, including 17 with primary open-angle
glaucoma, 19 with juvenile open-angle glaucoma, and 76 with normal tension
glaucoma. Healthy unrelated Korean individuals (n=100) were used as the non
selected population control. A total of three MYOC and four OPTN variants
potentially associated with primary glaucoma were identified in 4 and 18
patients, respectively. A novel variant of MYOC, p.Leu255Pro, was predicted to be
potentially pathogenic by in silico analysis. Another, p.Thr353Ile, has been
previously reported. These two missense variants were detected in patients with a
family history of glaucoma. Combined heterozygous variants p.[Thr123=;Ile288=]
were identified in 2 of 112 (2%) patients but not in healthy controls. Among OPTN
variants, a novel variant p.Arg271Cys was identified. Homozygous
p.[Thr34=;Thr34=] (4/112, 4%), homozygous p.[Met98Lys;Met98Lys] (4/112, 4%), or
combined heterozygous p.[Thr34=;Arg545Gln] (9/112, 8%) was significantly
associated with the development of primary glaucoma [odds ratio (OR)=8.768, 95%
confidence interval (CI)=1.972-38.988; relative risk=1.818, 95% CI=1.473-2.244;
P=0.001]. The present study provides insight into the genetic or haplotype
variants of MYOC and OPTN genes contributing to primary glaucoma. Haplotype
variants identified in the present study may be regarded as potential
contributing factors of primary glaucoma in Korea. Further studies, including
those on additional genes, are required to elucidate the underlying pathogenic
mechanism using a larger cohort to provide additional statistical power.
PMID- 27485218
TI - Biosynthesis of Carotenoids in Plants: Enzymes and Color.
AB - Carotenoids are the most important biocolor isoprenoids responsible for yellow,
orange and red colors found in nature. In plants, they are synthesized in
plastids of photosynthetic and sink organs and are essential molecules for
photosynthesis, photo-oxidative damage protection and phytohormone synthesis.
Carotenoids also play important roles in human health and nutrition acting as
vitamin A precursors and antioxidants. Biochemical and biophysical approaches in
different plants models have provided significant advances in understanding the
structural and functional roles of carotenoids in plants as well as the key
points of regulation in their biosynthesis. To date, different plant models have
been used to characterize the key genes and their regulation, which has increased
the knowledge of the carotenoid metabolic pathway in plants. In this chapter a
description of each step in the carotenoid synthesis pathway is presented and
discussed.
PMID- 27485217
TI - Carotenoid Distribution in Nature.
AB - Carotenoids are naturally occurring red, orange and yellow pigments that are
synthesized by plants and some microorganisms and fulfill many important
physiological functions. This chapter describes the distribution of carotenoid in
microorganisms, including bacteria, archaea, microalgae, filamentous fungi and
yeasts. We will also focus on their functional aspects and applications, such as
their nutritional value, their benefits for human and animal health and their
potential protection against free radicals. The central metabolic pathway leading
to the synthesis of carotenoids is described as the three following principal
steps: (i) the synthesis of isopentenyl pyrophosphate and the formation of
dimethylallyl pyrophosphate, (ii) the synthesis of geranylgeranyl pyrophosphate
and (iii) the synthesis of carotenoids per se, highlighting the differences that
have been found in several carotenogenic organisms and providing an evolutionary
perspective. Finally, as an example, the synthesis of the xanthophyll astaxanthin
is discussed.
PMID- 27485219
TI - Structures and Analysis of Carotenoid Molecules.
AB - Modifications of the usual C40 linear and symmetrical carotenoid skeleton give
rise to a wide array of structures of carotenes and xanthophylls in plant
tissues. These include acyclic, monocyclic and dicyclic carotenoids, along with
hydroxy and epoxy xanthophylls and apocarotenoids. Carotenols can be unesterified
or esterified (monoester) in one or two (diester) hydroxyl groups with fatty
acids. E-Z isomerization increases the array of possible plant carotenoids even
further. Screening and especially quantitative analysis are being carried out
worldwide. Visible absorption spectrometry and near infrared reflectance
spectroscopy have been used for the initial estimation of the total carotenoid
content or the principal carotenoid content when large numbers of samples needed
to be analyzed within a short time, as would be the case in breeding programs.
Although inherently difficult, quantitative analysis of the individual
carotenoids is essential. Knowledge of the sources of errors and means to avoid
them has led to a large body of reliable quantitative compositional data on
carotenoids. Reverse-phase HPLC with a photodiode array detector has been the
preferred analytical technique, but UHPLC is increasingly employed. HPLC-MS has
been used mainly for identification and NMR has been useful in unequivocally
identifying geometric isomers.
PMID- 27485220
TI - Carotenoids and Photosynthesis.
AB - Carotenoids are ubiquitous and essential pigments in photosynthesis. They absorb
in the blue-green region of the solar spectrum and transfer the absorbed energy
to (bacterio-)chlorophylls, and so expand the wavelength range of light that is
able to drive photosynthesis. This is an example of singlet-singlet energy
transfer, and so carotenoids serve to enhance the overall efficiency of
photosynthetic light reactions. Carotenoids also act to protect photosynthetic
organisms from the harmful effects of excess exposure to light. Triplet-triplet
energy transfer from chlorophylls to carotenoids plays a key role in this
photoprotective reaction. In the light-harvesting pigment-protein complexes from
purple photosynthetic bacteria and chlorophytes, carotenoids have an additional
role of structural stabilization of those complexes. In this article we review
what is currently known about how carotenoids discharge these functions. The
molecular architecture of photosynthetic systems will be outlined first to
provide a basis from which to describe carotenoid photochemistry, which underlies
most of their important functions in photosynthesis.
PMID- 27485221
TI - Regulation of Carotenoid Biosynthesis in Photosynthetic Organs.
AB - A substantial proportion of the dazzling diversity of colors displayed by living
organisms throughout the tree of life is determined by the presence of
carotenoids, which most often provide distinctive yellow, orange and red hues.
These metabolites play fundamental roles in nature that extend far beyond their
importance as pigments. In photosynthetic lineages, carotenoids are essential to
sustain life, since they have been exploited to maximize light harvesting and
protect the photosynthetic machinery from photooxidative stress. Consequently,
photosynthetic organisms have evolved several mechanisms that adjust the
carotenoid metabolism to efficiently cope with constantly fluctuating light
environments. This chapter will focus on the current knowledge concerning the
regulation of the carotenoid biosynthetic pathway in leaves, which are the
primary photosynthetic organs of most land plants.
PMID- 27485222
TI - Regulation of Carotenoid Biosynthesis During Fruit Development.
AB - Carotenoids are recognized as the main pigments in most fruit crops, providing
colours that range from yellow and pink to deep orange and red. Moreover, the
edible portion of widely consumed fruits or their derived products represent a
major dietary source of carotenoids for animals and humans. Therefore, these
pigments are crucial compounds contributing to fruit aesthetic and nutritional
quality but may also have protecting and ecophysiological functions in coloured
fruits. Among plant organs, fruits display one of the most heterogeneous
carotenoids patterns in terms of diversity and abundance. In this chapter a
comprehensive list of the carotenoid content and profile in the most commonly
cultivated fleshy fruits is reported. The proposed fruit classification systems
attending to carotenoid composition are revised and discussed. The regulation of
carotenoids in fruits can be rather complex due to the dramatic changes in
content and composition during ripening, which are also dependent on the fruit
tissue and the developmental stage. In addition, carotenoid accumulation is a
dynamic process, associated with the development of chromoplasts during ripening.
As a general rule, carotenoid accumulation is highly controlled at the
transcriptional level of the structural and accessory proteins of the
biosynthetic and degradation pathways, but other mechanisms such as post
transcriptional modifications or the development of sink structures have been
recently revealed as crucial factors in determining the levels and stability of
these pigments. In this chapter common key metabolic reactions regulating
carotenoid composition in fruit tissues are described in addition to others that
are restricted to certain species and generate unique carotenoids patterns. The
existence of fruit-specific isoforms for key steps such as the phytoene synthase,
lycopene beta-cyclases or catabolic carotenoid cleavage dioxygenases has allowed
an independent regulation of the pathway in fruit tissues and a source of
variability to create novel activities or different catalytic properties. Besides
key genes of the carotenoid pathway, changes in carotenoid accumulation could be
also directly influenced by differences in gene expression or protein activity in
the pathway of carotenoid precursors and some relevant examples are discussed.
The objective of this chapter is to provide an updated review of the main
carotenoid profiles in fleshy fruits, their pattern of changes during ripening
and our current understanding of the different regulatory levels responsible for
the diversity of carotenoid accumulation in fruit tissues.
PMID- 27485223
TI - Carotenoid Biosynthesis in Daucus carota.
AB - Carrot (Daucus carota) is one of the most important vegetable cultivated
worldwide and the main source of dietary provitamin A. Contrary to other plants,
almost all carrot varieties accumulate massive amounts of carotenoids in the
root, resulting in a wide variety of colors, including those with purple, yellow,
white, red and orange roots. During the first weeks of development the root,
grown in darkness, is thin and pale and devoid of carotenoids. At the second
month, the thickening of the root and the accumulation of carotenoids begins, and
it reaches its highest level at 3 months of development. This normal root
thickening and carotenoid accumulation can be completely altered when roots are
grown in light, in which chromoplasts differentiation is redirected to
chloroplasts development in accordance with an altered carotenoid profile. Here
we discuss the current evidence on the biosynthesis of carotenoid in carrot roots
in response to environmental cues that has contributed to our understanding of
the mechanism that regulates the accumulation of carotenoids, as well as the
carotenogenic gene expression and root development in D. carota.
PMID- 27485224
TI - Carotenoids in Microalgae.
AB - Carotenoids are a class of isoprenoids synthesized by all photosynthetic
organisms as well as by some non-photosynthetic bacteria and fungi with broad
applications in food, feed and cosmetics, and also in the nutraceutical and
pharmaceutical industries. Microalgae represent an important source of high-value
products, which include carotenoids, among others. Carotenoids play key roles in
light harvesting and energy transfer during photosynthesis and in the protection
of the photosynthetic apparatus against photooxidative damage. Carotenoids are
generally divided into carotenes and xanthophyls, but accumulation in microalgae
can also be classified as primary (essential for survival) and secondary (by
exposure to specific stimuli).In this chapter, we outline the high value
carotenoids produced by commercially important microalgae, their production
pathways, the improved production rates that can be achieved by genetic
engineering as well as their biotechnological applications.
PMID- 27485226
TI - Plastids and Carotenoid Accumulation.
AB - Plastids are ubiquitously present in plants and are the organelles for carotenoid
biosynthesis and storage. Based on their morphology and function, plastids are
classified into various types, i.e. proplastids, etioplasts, chloroplasts,
amyloplasts, and chromoplasts. All plastids, except proplastids, can synthesize
carotenoids. However, plastid types have a profound effect on carotenoid
accumulation and stability. In this chapter, we discuss carotenoid biosynthesis
and regulation in various plastids with a focus on carotenoids in chromoplasts.
Plastid transition related to carotenoid biosynthesis and the different capacity
of various plastids to sequester carotenoids and the associated effect on
carotenoid stability are described in light of carotenoid accumulation in plants.
PMID- 27485225
TI - Apocarotenoids: A New Carotenoid-Derived Pathway.
AB - Carotenoids are precursors of carotenoid derived molecules termed apocarotenoids,
which include isoprenoids with important functions in plant-environment
interactions such as the attraction of pollinators and the defense against
pathogens and herbivores. Apocarotenoids also include volatile aromatic compounds
that act as repellents, chemoattractants, growth simulators and inhibitors, as
well as the phytohormones abscisic acid and strigolactones. In plants,
apocarotenoids can be found in several types of plastids (etioplast, leucoplast
and chromoplast) and among different plant tissues such as flowers and roots. The
structural similarity of some flower and spice isoprenoid volatile organic
compounds (beta-ionone and safranal) to carotenoids has led to the recent
discovery of carotenoid-specific cleavage oxygenases, including carotenoid
cleavage dioxygenases and 9-cis-epoxydioxygenases, which tailor and transform
carotenoids into apocarotenoids. The great diversity of apocarotenoids is a
consequence of the huge amount of carotenoid precursors, the variations in
specific cleavage sites and the modifications after cleavage. Lycopene, beta
carotene and zeaxanthin are the precursors of the main apocarotenoids described
to date, which include bixin, crocin, picrocrocin, abscisic acid, strigolactone
and mycorradicin.The current chapter will give rise to an overview of the
biosynthesis and function of the most important apocarotenoids in plants, as well
as the current knowledge about the carotenoid cleavage oxygenase enzymes involved
in these biosynthetic pathways.
PMID- 27485227
TI - Evidence of Epigenetic Mechanisms Affecting Carotenoids.
AB - Epigenetic mechanisms are able to regulate plant development by generating non
Mendelian allelic interactions. An example of these are the responses to
environmenal stimuli that result in phenotypic variability and transgression
amongst important crop traits. The need to predict phenotypes from genotypes to
understand the molecular basis of the genotype-by-environment interaction is a
research priority. Today, with the recent discoveries in the field of
epigenetics, this challenge goes beyond analyzing how DNA sequences change. Here
we review examples of epigenetic regulation of genes involved in carotenoid
synthesis and degradation, cases in which histone- and/or DNA-methylation, and
RNA silencing at the posttranscriptional level affect carotenoids in plants.
PMID- 27485228
TI - Manipulation of Carotenoid Content in Plants to Improve Human Health.
AB - Carotenoids are essential components for human nutrition and health, mainly due
to their antioxidant and pro-vitamin A activity. Foods with enhanced carotenoid
content and composition are essential to ensure carotenoid feasibility in
malnourished population of many countries around the world, which is critical to
alleviate vitamin A deficiency and other health-related disorders. The pathway of
carotenoid biosynthesis is currently well understood, key steps of the pathways
in different plant species have been characterized and the corresponding genes
identified, as well as other regulatory elements. This enables the manipulation
and improvement of carotenoid content and composition in order to control the
nutritional value of a number of agronomical important staple crops.
Biotechnological and genetic engineering-based strategies to manipulate
carotenoid metabolism have been successfully implemented in many crops, with
Golden rice as the most relevant example of beta-carotene improvement in one of
the more widely consumed foods. Conventional breeding strategies have been also
adopted in the bio-fortification of carotenoid in staple foods that are highly
consumed in developing countries, including maize, cassava and sweet potatoes, to
alleviate nutrition-related problems. The objective of the chapter is to
summarize major breakthroughs and advances in the enhancement of carotenoid
content and composition in agronomical and nutritional important crops, with
special emphasis to their potential impact and benefits in human nutrition and
health.
PMID- 27485229
TI - Modern Breeding and Biotechnological Approaches to Enhance Carotenoid
Accumulation in Seeds.
AB - There is an increasing demand for carotenoids, which are fundamental components
of the human diet, for example as precursors of vitamin A. Carotenoids are also
potent antioxidants and their health benefits are becoming increasingly evident.
Protective effects against prostate cancer and age-related macular degeneration
have been proposed for lycopene and lutein/zeaxanthin, respectively.
Additionally, beta-carotene, astaxanthin and canthaxanthin are high-value
carotenoids used by the food industry as feed supplements and colorants. The
production and consumption of these carotenoids from natural sources, especially
from seeds, constitutes an important step towards fortifying the diet of
malnourished people in developing nations. Therefore, attempts to metabolically
manipulate beta-carotene production in plants have received global attention,
especially after the generation of Golden Rice (Oryza sativa). The endosperms of
Golden Rice seeds synthesize and accumulate large quantities of beta-carotene
(provitamin A), yielding a characteristic yellow color in the polished grains.
Classical breeding efforts have also focused in the development of cultivars with
elevated seed carotenoid content, with maize and other cereals leading the way.
In this communication we will summarize transgenic efforts and modern breeding
strategies to fortify various crop seeds with nutraceutical carotenoids.
PMID- 27485230
TI - Carotenoids as a Source of Antioxidants in the Diet.
AB - Carotenoids, widely distributed fat-soluble pigments, are responsible for the
attractive colorations of several fruits and vegetables commonly present in our
daily diet. They are particularly abundant in yellow-orange fruits (carrots,
tomatoes, pumpkins, peppers, among others) and, although masked by chlorophylls,
in dark green leafy vegetables. Several health benefits have been attributed to
carotenoids or to foods rich in these pigments, by means of different mechanisms
of-action, including the role as provitamin A of almost 50 different carotenoids
and the antioxidant activity that protects cells and tissues from damage of free
radicals and singlet oxygen, providing enhancement of the immune function,
protection from sunburn reactions and delaying the onset of certain types of
cancer. Common food sources and the efficiency of the absorption of carotenoids,
analytical approaches used for measurement of their antioxidant effect and an
overview of some epidemiological studies that have been performed to assess the
beneficial impact of carotenoids in human health are outlined in this chapter.
PMID- 27485231
TI - Carotenoids in Adipose Tissue Biology and Obesity.
AB - Cell, animal and human studies dealing with carotenoids and carotenoid
derivatives as nutritional regulators of adipose tissue biology with implications
for the etiology and management of obesity and obesity-related metabolic diseases
are reviewed. Most studied carotenoids in this context are beta-carotene,
cryptoxanthin, astaxanthin and fucoxanthin, together with beta-carotene-derived
retinoids and some other apocarotenoids. Studies indicate an impact of these
compounds on essential aspects of adipose tissue biology including the control of
adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress
and the production of adipose tissue-derived regulatory signals and inflammatory
mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis
and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in
brown and white adipocytes, and counteract obesity in animal models. Intake,
blood levels and adipocyte content of carotenoids are reduced in human obesity.
Specifically designed human intervention studies in the field, though still
sparse, indicate a beneficial effect of carotenoid supplementation in the accrual
of abdominal adiposity. In summary, studies support a role of specific
carotenoids and carotenoid derivatives in the prevention of excess adiposity, and
suggest that carotenoid requirements may be dependent on body composition.
PMID- 27485232
TI - Absorption of Carotenoids and Mechanisms Involved in Their Health-Related
Properties.
AB - Carotenoids participate in the normal metabolism and function of the human body.
They are involved in the prevention of several diseases, especially those related
to the inflammation syndrome. Their main mechanisms of action are associated to
their potent antioxidant activity and capacity to regulate the expression of
specific genes and proteins. Recent findings suggest that carotenoid metabolites
may explain several processes where the participation of their parent carotenoids
was unclear. The health benefits of carotenoids strongly depend on their
absorption and transformation during gastrointestinal digestion. The estimation
of the 'bioaccessibility' of carotenoids through in vitro models have made
possible the evaluation of the effect of a large number of factors on key stages
of carotenoid digestion and intestinal absorption. The bioaccessibility of these
compounds allows us to have a clear idea of their potential bioavailability, a
term that implicitly involves the biological activity of these compounds.
PMID- 27485233
TI - Transcriptome of the Caribbean stony coral Porites astreoides from three
developmental stages.
AB - BACKGROUND: Porites astreoides is a ubiquitous species of coral on modern
Caribbean reefs that is resistant to increasing temperatures, overfishing, and
other anthropogenic impacts that have threatened most other coral species. We
assembled and annotated a transcriptome from this coral using Illumina sequences
from three different developmental stages collected over several years: free
swimming larvae, newly settled larvae, and adults (>10 cm in diameter). This
resource will aid understanding of coral calcification, larval settlement, and
host-symbiont interactions. FINDINGS: A de novo transcriptome for the P.
astreoides holobiont (coral plus algal symbiont) was assembled using 594 Mbp of
raw Illumina sequencing data generated from five age-specific cDNA libraries. The
new transcriptome consists of 867 255 transcript elements with an average length
of 685 bases. The isolated P. astreoides assembly consists of 129 718 transcript
elements with an average length of 811 bases, and the isolated Symbiodinium sp.
assembly had 186 177 transcript elements with an average length of 1105 bases.
CONCLUSIONS: This contribution to coral transcriptome data provides a valuable
resource for researchers studying the ontogeny of gene expression patterns within
both the coral and its dinoflagellate symbiont.
PMID- 27485234
TI - The Manchester procedure versus vaginal hysterectomy in the treatment of uterine
prolapse: a review.
AB - INTRODUCTION AND HYPOTHESIS: Uterine prolapse is a common health problem and the
number of surgical procedures is increasing. No consensus regarding the surgical
strategy for repair of uterine prolapse exists. Vaginal hysterectomy (VH) is the
preferred surgical procedure worldwide, but uterus-preserving alternatives
including the Manchester procedure (MP) are available. The objective was to
evaluate if VH and the MP are equally efficient treatments for uterine prolapse
with regard to anatomical and symptomatic outcome, quality of life score,
functional outcome, re-operation and conservative re-intervention rate,
complications and operative outcomes. METHODS: We systematically searched Embase,
PubMed, the Cochrane databases, Clinicaltrials and Clinical trials register using
the MeSh terms "uterine prolapse", "uterus prolapse", "vaginal prolapse" "pelvic
organ prolapse", "prolapsed uterus", "Manchester procedure" and "vaginal
hysterectomy". No limitations regarding language, study design or methodology
were applied. In total, nine studies published from 1966 to 2014 comparing the MP
to VH were included. RESULTS: The anatomical recurrence rate for the middle
compartment was 4-7 % after VH, whereas recurrence was very rare after the MP.
The re-operation rate because of symptomatic recurrence was higher after VH (9
13.1 %) compared with MP (3.3-9.5 %) and more patients needed conservative re
intervention (14-15 %) than after MP (10-11 %). After VH, postoperative bleeding
and blood loss tended to be greater, bladder lesions and infections more frequent
and the operating time longer. CONCLUSIONS: This review is in favour of the MP,
which seems to be an efficient and safe treatment for uterine prolapse. We
suggest that the MP might be considered a durable alternative to VH in uterine
prolapse repair.
PMID- 27485235
TI - Is Immunomodulation a Principal Mechanism Underlying How Cell-Based Therapies
Enhance Stroke Recovery?
AB - Inflammation within the brain and in peripheral tissues contributes to brain
injury following ischemic stroke. Therapeutic modulation of the inflammatory
response has been actively pursued as a novel stroke treatment approach for
decades, without success. In recent years, extensive studies support the high
potential for cell-based therapies to become a new treatment modality for stroke
and other neurological disorders. In this review, we explore different types of
cellular therapies and discuss how they modulate central and peripheral
inflammatory processes after stroke. Apart from identifying potential targets for
cell therapy, we also discuss paracrine and immunomodulatory mechanisms of cell
therapy.
PMID- 27485236
TI - Prophylactic Antibiotic Therapy for Preventing Poststroke Infection.
AB - Infections, in particular pneumonia, are common complications in patients with
acute stroke and are associated with a less favorable neurologic and functional
outcome. Patients with severe stroke and dysphagia are at highest risk of
infection. Experimental and clinical data suggest stroke-induced immunodeficiency
as a major factor contributing to the high incidence of infection after stroke.
Preclinical studies support the potential benefit of preventive antibiotic
therapy in acute stroke for lowering the incidence of infection and improving
clinical outcome. Several smaller clinical trials on preventive antibiotic
therapy in patients with stroke conducted during the last 10 years yielded
inconclusive results. Recently, 2 large, open-label, controlled trials failed to
demonstrate an improved clinical outcome after preventive antibiotic therapy in
patients with acute stroke treated in specialized stroke units. In the
"Preventive Antibiotics in Stroke Study", antibiotic therapy lowered the rate of
infection but did not influence outcome. In the STROKE-INF study, performed in
patients with dysphagia after stroke, antibiotic therapy did not lower the
incidence of pneumonia and had no prognostic significance. At present, preventive
antibiotic therapy cannot be recommended as a therapeutic option for acute
stroke.
PMID- 27485237
TI - Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker
Muscular Dystrophy.
AB - Patients suffering from Becker muscular dystrophy (BMD) have dysfunctional
dystrophin proteins and are deficient in neuronal nitric oxide synthase (nNOS) in
muscles. This causes functional ischemia and contributes to muscle wasting.
Similar functional ischemia may be present in brains of patients with BMD, who
often have mild cognitive impairment, and nNOS may be important for the
regulation of the microvascular circulation in the brain. We hypothesized that
treatment with sildenafil, a phosphodiesterase type 5 inhibitor that potentiates
nitric oxide responses, would augment both the blood oxygen level-dependent
(BOLD) response and cerebral blood flow (CBF) in patients with BMD. Seventeen
patients (mean +/- SD age 38.5 +/- 10.8 years) with BMD were included in this
randomized, double-blind, placebo-controlled, crossover trial. Twelve patients
completed the entire study. Effects of sildenafil were assessed by 3 T magnetic
resonance (MR) scanning, evoked potentials, somatosensory task-induced BOLD
functional MR imaging, regional and global perfusion, and angiography before and
after 4 weeks of sildenafil, 20 mg (Revatio in gelatine capsules, oral, 3 times
daily), or placebo treatment. Sildenafil increased the event-related sensory and
visual BOLD response compared with placebo (p < 0.01). However, sildenafil did
not alter CBF, measured by MR phase contrast mapping, or the arterial diameter of
the middle cerebral artery, measured by MR angiography. We conclude that nNOS may
play a role in event-related neurovascular responses. Further studies in patients
with BMD may help clarify the roles of dystrophin and nNOS in neurovascular
coupling in general, and in patients with BMD in particular.
PMID- 27485239
TI - Maternal Sleep Quality and Diurnal Cortisol Regulation Over Pregnancy.
AB - Poor sleep in pregnancy is related to adverse neonatal health. Elevated maternal
cortisol has been proposed as a pathway, yet the association in pregnancy is not
well understood. The goals of the current study were to examine associations
between (a) sleep and cortisol, (b) sleep, cortisol, and neonatal outcomes, and
(c) variables that could explain these associations. Two hundred pregnant women
completed the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk,
Berman, & Kupfer, 1989) and provided diurnal salivary cortisol samples at two
times over pregnancy. Poor sleep quality was associated with greater evening
cortisol concentrations at 36 weeks' gestation. This association was mediated by
anxiety symptoms. Higher evening cortisol at 36 weeks' gestation was associated
with shorter gestation.
PMID- 27485240
TI - Brief report on a systematic review of youth violence prevention through media
campaigns: Does the limited yield of strong evidence imply methodological
challenges or absence of effect?
AB - BACKGROUND: We present a brief report on a systematic review which identified,
assessed and synthesized the existing evidence of the effectiveness of media
campaigns in reducing youth violence. METHODS: Search strategies made use of
terms for youth, violence and a range of terms relating to the intervention. An
array of academic databases and websites were searched. RESULTS: Although media
campaigns to reduce violence are widespread, only six studies met the inclusion
criteria. There is little strong evidence to support a direct link between media
campaigns and a reduction in youth violence. Several studies measure proxies for
violence such as empathy or opinions related to violence, but the link between
these measures and violence perpetration is unclear. Nonetheless, some evidence
suggests that a targeted and context-specific campaign, especially when combined
with other measures, can reduce violence. However, such campaigns are less cost
effective to replicate over large populations than generalised campaigns.
CONCLUSIONS: It is unclear whether the paucity of evidence represents a null
effect or methodological challenges with evaluating media campaigns. Future
studies need to be carefully planned to accommodate for methodological
difficulties as well as to identify the specific elements of campaigns that work,
especially in lower and middle income countries.
PMID- 27485241
TI - Antenatal care use in urban areas in two European countries: Predisposing,
enabling and pregnancy-related determinants in Belgium and the Netherlands.
AB - BACKGROUND: Examining determinants of antenatal care (ANC) is important to
stimulate equitable distribution of ANC across Europe. This study (1) compares
ANC utilisation in Belgium and the Netherlands and (2) identifies predisposing,
enabling and pregnancy-related determinants. METHODS: Secondary data analysis is
performed using data from Belgium, and the Netherlands. The content and timing of
care during pregnancy (CTP) tool measured ANC use. Non-parametric tests and
ordinal logistic regression are performed to gain insight in the determinants of
health care use. RESULTS: Dutch women receive appropriate ANC more often than
Belgian women. Multivariate analysis showed that lower education, unemployment,
lower continuity of care and non-attendance of antenatal classes are associated
with a lower likelihood of having more appropriate ANC. CONCLUSIONS: Predisposing
and pregnancy related variables are most important to influence the content and
timing of ANC, irrespective of the country women live in. Lower health literacy
in socially vulnerable women might explain the predisposing determinants of
health care use in both countries. Stimulating accessibility to antenatal courses
or organising public education are recommendations for practice. Regarding
pregnancy-related determinants, improving continuity of care can optimise ANC use
in both countries.
PMID- 27485238
TI - Microglia and Monocyte-Derived Macrophages in Stroke.
AB - Historically, the brain has been considered an immune-privileged organ separated
from the peripheral immune system by the blood-brain barrier. However, immune
responses do occur in the brain in neurological conditions in which the integrity
of the blood-brain barrier is compromised, exposing the brain to peripheral
antigens and endogenous danger signals. While most of the associated pathological
processes occur in the central nervous system, it is now clear that peripheral
immune cells, especially mononuclear phagocytes, that infiltrate into the injury
site play a key role in modulating the progression of primary brain injury
development. As inflammation is a necessary and critical component for the
subsequent injury resolution process, understanding the contribution of
mononuclear phagocytes on the regulation of inflammatory responses may provide
novel approaches for potential therapies. Furthermore, predisposed comorbid
conditions at the time of stroke cause the alteration of stroke-induced immune
and inflammatory responses and subsequently influence stroke outcome. In this
review, we summarize a role for microglia and monocytes/macrophages in acute
ischemic stroke in the context of normal and metabolically compromised
conditions.
PMID- 27485243
TI - Weight-Related Goal Setting in a Telephone-Based Preventive Health-Coaching
Program: Demonstration of Effectiveness.
AB - PURPOSE: This study investigated whether participants in a 6-month telephone
based coaching program, who set physical activity, nutrition, and weight loss
goals had better outcomes in these domains. DESIGN: Quasi-experimental design.
SETTING: The Australian Get Healthy Information and Coaching Service (GHS), a
free population-wide telephone health-coaching service that includes goal setting
as a key component of its coaching program. PARTICIPANTS: Consenting GHS coaching
participants who had completed coaching between February 2009 and December 2012
(n = 4108). MEASURES: At baseline, participants select a goal for the coaching
program, and sociodemographic variables are collected. Self-reported weight,
height, waist circumference, physical activity, and nutrition-related behaviors
are assessed at baseline and 6 months. ANALYSIS: Descriptive analysis was
performed on key sociodemographic variables, and the relationship between goal
type and change in health outcomes was assessed using a series of linear mixed
models that modeled change from baseline to 6 months. RESULTS: Participants who
set goals in relation to weight management and physical activity achieved better
results in these areas than those who set alternate goals, losing more than those
who set alternate goals (1.5 kg and 0.9 cm in waist circumference) and increasing
walking per week (40 minutes), respectively. There was no difference in food
related outcomes for those that set nutrition-related goals. CONCLUSION: Goal
setting for weight management and increasing physical activity in the overweight
and obese population, undertaken in a telephone-based coaching program, can be
effective.
PMID- 27485242
TI - The skin microbiome in allergen-induced canine atopic dermatitis.
AB - BACKGROUND: Studies focusing on next-generation sequencing of the bacterial 16S
rRNA gene have allowed detailed surveys of skin bacterial populations
(microbiota) of the skin. HYPOTHESIS/OBJECTIVES: This study evaluated temporal
changes in the skin microbiota in a canine model of atopic dermatitis. ANIMALS:
Eight atopic dogs previously sensitized with house dust mites (HDM). METHODS: The
dogs were topically challenged on the right groin with HDM allergens. Swabs were
collected from the challenged and the contralateral nonchallenged sites prior to
provocation (pre-challenge; baseline sample) and on days 1, 7, 14, 21 and 28
after allergen challenge. The 16S rRNA gene was amplified, sequenced and
analysed. Staphylococcus spp. and Staphylococcus pseudintermedius were quantified
with quantitative PCR (RT-qPCR). RESULTS: Skin lesions developed in all dogs on
the challenged sites. Differences in bacterial groups were observed on the
challenged site over time. Relatively lower abundances of Fusobacteriaceae on Day
7, and, based on LEfSe, increased abundances of Corynebacteriaceae on Day 1, and
Staphylococcaceae on days 7, 14 and 21, were observed on the challenged site,
compared to the contralateral site. Results of RT-qPCR correlated with those of
next-generation sequencing, with significantly increased numbers of
Staphylococcus spp. and S. pseudintermedius on Day 21, and days 7 and 21 on the
challenged site compared to the contralateral site, respectively. CONCLUSIONS AND
CLINICAL IMPORTANCE: This study demonstrates that an allergen challenge in
sensitized dogs leads to bacterial dysbiosis with increased abundance of S.
pseudintermedius at the site of lesion induction.
PMID- 27485244
TI - Phenomenological theory of uniaxial relaxor ferroelectrics.
AB - A phenomenological thermodynamic theory of uniaxial relaxor strontium barium
niobate [Formula: see text] is developed using the Landau-Devonshire approach
with two order parameters. The fourth-order thermodynamic potential allowed to
explain the shape of the polarization hysteresis loops experimentally observed at
different temperatures. We show that the broad maximum of the dielectric
permittivity is not related to the phase transition and arise due to the coupling
between polarization and true order parameter which has antiferroelectric nature.
We found that the phase transition temperature is much higher than the maximum of
the dielectric permittivity and very likely corresponds to so-called Burn's
temperature. True order parameter has no simple relation with polar modes.
PMID- 27485245
TI - Pulling it all together: The road to lasting bilingualism for children with
developmental disabilities.
AB - Children with DD must and do become bilingual, but the research reported in this
special issue raises questions about equitable access to bilingual opportunities
and provision of appropriate supports to ensure optimal bilingual growth in these
children. The purpose of the present article was to apply the findings from our
international collaboration to inform policy and practice on bilingualism in
children with developmental disabilities (DD). To do this, we first overview the
research presented in detail in other articles of this special issue: a narrative
literature review, a review of site policies and practices related to special
education and language education, a qualitative analysis of key informant
interviews, and a quantitative analysis of surveys of practitioners. From these
overviews emerge a complex set of contextual factors that impact bilingual
development in children with DD. We then use the Bioecological Systems model of
Bronfenbrenner and Morris (2007) and conceptual maps (C-maps) to examine the
particular circumstances of three hypothetical children with DD who are in very
different bilingual contexts. In so doing, areas of both positive and negative
influence on lasting bilingualism are identified for each child. We end with
recommendations for increasing access to and support for bilingualism in children
with DD.
PMID- 27485246
TI - Functional independence measure for elderly patients undergoing aortic valve
replacement.
AB - OBJECTIVE: This study aimed to evaluate the efficacy of the Functional
Independence Measure to assess preoperative frailty for elderly patients
undergoing surgical aortic valve replacement. METHODS: Eighty-five patients >65
years who survived elective isolated aortic valve replacement from January 2008
to October 2015 were included. The mean age at the operation was 78 +/- 6 years
old (n = 28 males, n = 57 females). The patients were divided into two groups
according to their status at discharge: impossible to discharge home or
hospitalization for >30 days (compromised group, n = 8), or unaffected
(unaffected group, n = 77). Preoperative frailty was evaluated with the
Functional Independence Measure, which comprises 18 items divided into six
domains: self-care, sphincter control, mobility, locomotion, communication, and
social cognition. RESULTS: The preoperative total Functional Independence Measure
score was significantly lower in the compromised group (79 +/- 32) than in the
unaffected group (120 +/- 9, p < 0.01). The preoperative motor Functional
Independence Measure score was significantly lower in the compromised group (45
+/- 24) than in the unaffected group (85 +/- 9, p = <0.01). The duration of
postoperative intubation, intensive care unit stay, and postoperative
hospitalization were significantly longer in the compromised group than in the
unaffected group (48 +/- 67 vs 16 +/- 12 h, p < 0.01; 6.7 +/- 5.3 vs 3.4 +/- 2.0
days, p < 0.01; 34 +/- 27 vs 23 +/- 11 days, p = 0.02, respectively).
CONCLUSIONS: The preoperative Functional Independence Measure is effective for
assessing preoperative frailty in elderly patients undergoing aortic valve
replacement in terms of predicting operative morbidity.
PMID- 27485247
TI - Predictors of patent false lumen of the aortic arch after hemiarch replacement.
AB - BACKGROUND: Hemiarch replacement for acute type A aortic dissection is less
invasive than total arch replacement but involves increased risk of late aortic
arch dilation because of patent false lumen of the aortic arch. If we can predict
this risk, it may be a valuable prognostic indicator for selecting surgical
procedures for acute type A aortic dissection. METHODS: We reviewed our surgical
experience to predict patent false lumen. From January 2009 to November 2014, we
performed 108 hemiarch replacement procedures for acute type A aortic dissection
that had patent false lumen of the ascending aortic arch. We identified 56
patients who had preoperative and postoperative contrast-enhanced computed
tomography. Patients' preoperative characteristics, preoperative and
postoperative contrast-enhanced computed tomography findings, intraoperative
findings and postoperative course were investigated. RESULTS: Of the 56 patients,
32 (57.1 %) were men and their mean age at surgery was 63.7 +/- 11.8 years.
Overall in-hospital mortality rate was 7.1 % (4 patients). According to
postoperative imaging findings, 56 patients were classified into two groups:
group A (39 patients), with patent false lumen, and group B (17 patients), with
thrombosed false lumen. Logistic regression analysis revealed that
brachiocephalic artery dissection and no tear resection contributed to
postoperative patent false lumen of the aortic arch more strongly than did other
factors. CONCLUSIONS: Brachiocephalic artery dissection and no tear resection are
potential predictors of patent false lumen of the aortic arch after hemiarch
replacement.
PMID- 27485248
TI - Preoperative simulation of minimally invasive aortic valve replacement using
patient-specific replica.
AB - Exposure of surgeons to minimally invasive cardiac surgery is typically limited.
We developed a patient-specific aortic root silicon replica for simulating
minimally invasive aortic valve replacement (MIAVR). From this 3D model,
important anatomical information was obtained. To understand the best procedural
option, different techniques were attempted without time limitation, leading to
the complete planning of the operation. The patient-specific replica and
simulated surgery were useful for preoperative training and planning for the
MIAVR procedure.
PMID- 27485249
TI - Impact of the size mismatch between saphenous vein graft and coronary artery on
graft patency.
AB - BACKGROUND: The saphenous vein graft (SVG) is widely used in coronary artery
bypass grafting because of its availability and ease of use. However, the patency
rate of the SVG grafted to the right coronary artery (RCA) is poor. Diameter
mismatch between the coronary artery and SVG is an important cause of graft
occlusion. In this study, we assessed how the degree of diameter mismatch affects
SVG patency. METHODS: We reviewed the records of 123 patients who underwent aorto
right coronary artery bypass grafting with an SVG. The patency rate of the SVG,
SVG diameter, RCA diameter and SVG-RCA diameter ratio (SR ratio) was assessed
based on angiography and CT. RESULTS: The mean SVG diameter was 3.61 +/- 0.72 mm,
the mean RCA diameter was 1.57 +/- 0.32 mm and the mean SR ratio was 2.37 +/-
0.57. Cumulative patency rate of the SVG was 95.5 % at the early phase, 85.2 % at
1 year, and 70.2 % at 5 years. Multivariate analysis showed that the SR ratio was
an independent predictor of SVG occlusion. The cutoff value of the SR ratio was
2.8, calculated from the point of maximal specificity (81.2 %) and sensitivity
(64.7 %), and the area under the ROC curve was 0.734. When the SR ratio was
<=2.8, the 3-year patency rate was 86.1 %. CONCLUSIONS: A mismatch between SVG
diameter and RCA diameter has an impact on the patency rate of the SVG.
Evaluation of the saphenous vein before surgery and selection of a graft to
minimize mismatch should improve SVG patency.
PMID- 27485250
TI - Premature mammary gland involution with repeated corticosterone injection in
interleukin 10-deficient mice.
AB - Recently, we found that maternal stress could induce premature mammary gland
involution in interleukin 10 knock out (IL-10-/-) mice. To elucidate correlation
between stress, IL-10, and mammary gland involution, corticosterone was injected
into the lactating wild type and IL-10-deficient mice and assessed mammary gland
phenotype. Repetitive corticosterone injection developed premature mammary gland
involution only in B6.IL-10-/- mice; moreover, it induced alopecia in nursing
pups. Corticosterone injection induced several typical changes such as mammary
gland epithelial cell apoptosis, macrophage infiltration, fat deposition in
adipocyte, STAT3 phosphorylation, and upregulation of tyrosine hydroxylase gene
in adrenal gland. Overall incidence of pup alopecia and mammary gland involution
was relatively high in corticosterone than control B6.IL-10-/- group (57% vs.
20%). Our finding demonstrates that IL-10 is important for stress modulation, and
B6.Il-10-/- with corticosterone has several advantage such as simple to
establish, well-defined onset of mammary gland involution, high incidence, and
inducing pup alopecia.
PMID- 27485251
TI - Minimally invasive microneedles for ocular drug delivery.
AB - INTRODUCTION: Anterior and posterior segment eye diseases are highly challenging
to treat, due to the barrier properties and relative inaccessibility of the
ocular tissues. Topical eye drops and systemically delivered treatments result in
low bioavailability. Alternatively, direct injection of medication into the
ocular tissues is clinically employed to overcome the barrier properties, but
injections cause significant tissue damage and are associated with a number of
untoward side effects and poor patient compliance. Microneedles (MNs) has been
recently introduced as a minimally invasive means for localizing drug formulation
within the target ocular tissues with greater precision and accuracy than the
hypodermic needles. Areas covered: This review article seeks to provide an
overview of a range of challenges that are often faced to achieve efficient
ocular drug levels within targeted tissue(s) of the eye. It also describes the
problems encountered using conventional hypodermic needle-based ocular injections
for anterior and posterior segment drug delivery. It discusses research carried
out in the field of MNs, to date. Expert opinion: MNs can aid in localization of
drug delivery systems within the selected ocular tissue. And, hold the potential
to revolutionize the way drug formulations are administered to the eye. However,
the current limitations and challenges of MNs application warrant further
research in this field to enable its widespread clinical application.
PMID- 27485252
TI - When less could be more: Investigating the effects of a brief internet-based
imagery cognitive bias modification intervention in depression.
AB - Depression is a highly prevalent condition worldwide, yet multiple barriers to
treatments means that the development of low intensive and easily accessible
psychological interventions is crucially needed. The current study sought to
investigate the efficacy of a brief, self-administered imagery cognitive bias
modification (imagery CBM) procedure delivered online to a sample of 101
individuals with depressive symptoms. Compared to a closely matched control
condition or a waitlist condition, imagery CBM led to greater improvements in
depressive symptoms (d = 0.86, 95% CI = [0.33, 1.3] and d = 1.17, 95% CI = [0.62,
1.65]) interpretation bias and anhedonia. Despite the limitation to a two week
follow-up, the study findings highlight the potential of imagery CBM as a brief,
easily accessible intervention for depression that can be delivered remotely in
peoples' home.
PMID- 27485253
TI - Evaluation of synergistic effects of sulforaphene with photodynamic therapy in
human cervical cancer cell line.
AB - Sulforaphene from cruciferous vegetable has shown to modulate various signaling
pathways of apoptosis. But it has not yet been studied extensively for the
cervical cancer treatment. Previous studies show the promising role of
photodynamic therapy for cervical cancer. Here, we confirm that sulforaphene can
synergistically enhance the efficacy of photodynamic therapy. Human cervical
cancer cells HeLa were treated with a very low dose of sulforaphene (2.0 MUg/ml)
and photodynamic therapy with radachlorin (0.5 MUg/ml) at a fluence of 27 J/cm2
(30 milliwatts/cm2, lambdamax ~ 670 +/- 3 nm). The combination treatment showed a
synergistic effect to induce apoptosis. The mitochondrial apoptotic pathway was
activated via caspase 3 and caspase 9. On the other hand, caspase 12 and C/EBP
homologous protein (CHOP) were expressed that indicated endoplasmic reticulum
stress. This combination treatment also activated death receptor pathway via
activation of caspase 8 and inhibited cell proliferation via down-regulation of
EGFR. Thus, several apoptotic pathways were simultaneously activated in this
combination treatment which results in a synergistic efficacy of sulforaphene
with photodynamic therapy. Therefore, this study could be useful in the
improvement of therapies for human cervical and other types of cancers.
PMID- 27485255
TI - Local thermal sensation modeling-a review on the necessity and availability of
local clothing properties and local metabolic heat production.
AB - Local thermal sensation modeling gained importance due to developments in
personalized and locally applied heating and cooling systems in office
environments. The accuracy of these models depends on skin temperature prediction
by thermophysiological models, which in turn rely on accurate environmental and
personal input data. Environmental parameters are measured or prescribed, but
personal factors such as clothing properties and metabolic rates have to be
estimated. Data for estimating the overall values of clothing properties and
metabolic rates are available in several papers and standards. However, local
values are more difficult to retrieve. For local clothing, this study revealed
that full and consistent data sets are not available in the published literature
for typical office clothing sets. Furthermore, the values for local heat
production were not verified for characteristic office activities, but were
adapted empirically. Further analyses showed that variations in input parameters
can lead to local skin temperature differences (?Tskin,loc = 0.4-4.4 degrees C).
These differences can affect the local sensation output, where ?Tskin,loc = 1
degrees C is approximately one step on a 9-point thermal sensation scale. In
conclusion, future research should include a systematic study of local clothing
properties and the development of feasible methods for measuring and validating
local heat production.
PMID- 27485254
TI - Rapid Detection of Cyprinid Herpesvirus 3 in Latently Infected Koi by Recombinase
Polymerase Amplification.
AB - Since the emergence of cyprinid herpesvirus 3 (CyHV-3), outbreaks have been
devastating to Common Carp Cyprinus carpio and koi (a variant of Common Carp),
leading to high economic losses. Current diagnostics for detecting CyHV-3 are
limited in sensitivity and are further complicated by latency. Here we describe
the detection of CyHV-3 by recombinase polymerase amplification (RPA). The RPA
assay can detect as low as 10 copies of the CyHV-3 genome by an isothermal
reaction and yields results in approximately 20 min. Using the RPA assay, the
CyHV-3 genome can be detected in the total DNA of white blood cells isolated from
koi latently infected with CyHV-3, while less than 10% of the latently infected
koi can be detected by a real-time PCR assay in the total DNA of white blood
cells. In addition, RPA products can be detected in a lateral flow device that is
cheap and fast and can be used outside of the diagnostic lab. The RPA assay and
lateral flow device provide for the rapid, sensitive, and specific amplification
of CyHV-3 that with future modifications for field use and validation could lead
to enhanced surveillance and early diagnosis of CyHV-3 in the laboratory and
field. Received September 14, 2015; accepted April 9, 2016.
PMID- 27485256
TI - Simple and rapid characterization of novel large germline deletions in SDHB, SDHC
and SDHD-related paraganglioma.
AB - Germline mutations in genes encoding subunits of succinate dehydrogenase (SDH)
are associated with hereditary paraganglioma and pheochromocytoma. Although most
mutations in SDHB, SDHC and SDHD are intraexonic variants, large germline
deletions may represent up to 10% of all variants but are rarely characterized at
the DNA sequence level. Additional phenotypic effects resulting from deletions
that affect neighboring genes are also not understood. We performed multiplex
ligation-dependent probe amplification, followed by a simple long-range PCR
'chromosome walking' protocol to characterize breakpoints in 20 SDHx-linked
paraganglioma-pheochromocytoma patients. Breakpoints were confirmed by
conventional PCR and Sanger sequencing. Heterozygous germline deletions of up to
104 kb in size were identified in SDHB, SDHC, SDHD and flanking genes in 20
paraganglioma-pheochromocytoma patients. The exact breakpoint could be determined
in 16 paraganglioma-pheochromocytoma patients of which 15 were novel deletions.
In six patients proximal genes were also deleted, including PADI2, MFAP2, ATP13A2
(PARK9), CFAP126, TIMM8B and C11orf57. These genes were either partially or
completely deleted, but did not modify the phenotype. This study increases the
number of known SDHx deletions by over 50% and demonstrates that a significant
proportion of large gene deletions can be resolved at the nucleotide level using
a simple and rapid method.
PMID- 27485257
TI - Utilizing single- and double-transfected cell models expressing human organic
anion transporter 1 and human cytochrome P450 1A2 to investigate the interactions
with ingredients of herbal medicines.
AB - 1. Cell models expressing human drug transporters and enzymes are useful tools to
understand the process of drug disposition in vitro. However, no study on
transfected cells stably co-expressing human organic anion transporter 1 (hOAT1)
and/or human cytochrome P450 1A2 (hCYP1A2) is available. In this study, cell
models stably expressing hOAT1 and/or hCYP1A2 were established, and were used to
investigate the interactions of ingredients of herbal medicines (IHMs) with hOAT1
and/or hCYP1A2. 2. The MDCK cells were stable transfected with recombinant
plasmids expressing hOAT1 and/or hCYP1A2. Cellular uptake assay and CYP450
activity assay showed that the transfected cells were available. A marked high
expression of hOAT1 and hCYP1A2 mRNA was also validated by quantitative RT-PCR.
Totally 6 IHMs which significantly inhibited the activity of hOAT1 were screened
out by employing hOAT1 expressing cells. The contribution of hOAT1 and hCYP1A2 to
the toxicity of aristolochic acid I (AAI) was further determined. Compared to
mock cells, all transfected cells showed a decrease in viability after being
treated with AAI. 3. A method to establish transfected cell expressing drug
metabolism enzymes and/or transporters was provided in our study. Three IHMs
(dihydrotanshinone I, cryptotanshinone, and tanshinone I) were confirmed as novel
inhibitors of hOAT1. Furthermore, a synergistic effect of hOAT1 and hCYP1A2 on
AAI-induced toxicity was also observed in this investigation.
PMID- 27485259
TI - Long-term care in Spain: Difficulties in professionalizing services.
AB - The aim of this article is to analyze the difficulties in professionalizing the
long-term care system in Spain. Since 2006, the new Spanish law has recognized
care as a subjective right, and regulations are being designed to create a
framework for its professionalization. Nowadays, family remains the most
important group of providers who care for their elders, and women remain the main
informal caregivers. Why do families resist using public long-term care services
and professional carers included in the new law? The hypothesis highlights
sociocultural factors as an obstacle to professionalization of long-term care
services in addition to political and economic factors. The results show
qualitative data about expectations, preferences, and discourses that women
caregivers have in relation to their responsibility. The empirical material
includes 25 interviews with different profiles of caregivers and six focus groups
with family caregivers. The article suggests that the Spanish ideal of care is a
problem for the professionalization of services because the family remains as the
main provider of care-without specific skills, knowledge, and abilities.
PMID- 27485260
TI - Positive Feelings After Casual Sex: The Role of Gender and Traditional Gender
Role Beliefs.
AB - The purpose of this study was to identify predictors of positive and negative
affect following casual sex. Specifically, the primary goal was to investigate
how traditional gender-role beliefs, peer approval of casual sex, perceptions of
others, sexual assertiveness, and sexual pleasure influence affective
experiences. Second, we aimed to determine the extent to which these associations
were comparable for men and women. Although we expected mean differences on many
of these constructs (e.g., men perceiving more peer approval), we expected the
relationships between these constructs to be comparable for women and men.
Participants ages 18 to 35 (N = 585) were recruited from a large university and
Amazon Mechanical Turk (MTurk) and described their most recent casual sex
experience in a self-report questionnaire. Structural equation modeling (SEM)
analyses indicated that gender-role beliefs were significantly associated with
less sexual assertiveness and more negative perceptions of others; for women they
were also associated with less peer approval of casual sex. For women and men,
sexual assertiveness predicted sexual pleasure; and sexual pleasure was
associated with affect. To decrease the gender discrepancy in positive affect and
sexual pleasure, it is important to develop a comprehensive understanding of the
interrelationships among norms, casual sex experiences, and affect.
PMID- 27485261
TI - Role of physician perception of patient smile on pretest probability assessment
for acute pulmonary embolism.
AB - BACKGROUND: Many clinicians use a global visual interpretation of patient
appearance to decide if a patient looks sick or not. For patients with suspected
acute pulmonary embolism (PE), we tested the relationship between visual
appearance of a happy patient facial affect and probability of PE+ on CT
pulmonary angiography (CTPA). METHODS: Eligible patients were selected by usual
care to undergo CTPA, the criterion standard for PE+ or PE-. Prior to CTPA
result, trained study personnel obtained physician pretest probability using the
gestalt method (visual analogue scale, 0%-100%), the Wells score (0-12) and
physicians' impression of whether the patient smiled during the initial
examination (smile+). Patients' faces were also video recorded and analysed with
an automated neural network-based algorithm (Noldus FaceReader) for happy affect.
RESULTS: Of the 208 patients enrolled, 27 were PE+ and smile+ was more frequent
in patients with PE+ than PE-, a finding confirmed by the Noldus. The diagnostic
sensitivity and specificity of smile was low, and physicians overestimated
presence of an alternative diagnosis more likely to PE with smile+ than smile-
patients in patients with true PE. As a result, the area under the receiver
operating characteristic curve (AUROC) was lower for the Wells score in smile+
patients. However, the physicians' mean gestalt estimate of PE did not differ
with smile status, nor did smile status affect the AUROC for gestalt.
CONCLUSIONS: In patients with suspected PE, physician recollection of patients'
smile+ was more common in PE+ patients, and was associated with a less accurate
Wells score, primarily because physicians overestimated probability of
alternative diagnosis. However, the overall diagnostic accuracy of physicians'
gestalt did not differ with perceived smile status. These data suggest that the
patients' smile had less effect on the numeric gestalt pretest probability
assessment than on the binary decision about an alternative diagnosis.
PMID- 27485262
TI - Out-of-hospital cardiac arrest attended by ambulance services in Ireland: first 2
years' results from a nationwide registry.
AB - BACKGROUND: National data collection provides information on out-of-hospital
cardiac arrest (OHCA) incidence, management and outcomes that may not be
generalisable from smaller studies. This retrospective cohort study describes the
first 2 years' results from the Irish National Out-of-Hospital Cardiac Arrest
Register (OHCAR). METHODS: Data on OHCAs attended by emergency medical services
(EMS) where resuscitation was attempted (EMS-treated) were collected from
ambulance services and entered onto OHCAR. Descriptive analysis of the study
population was performed, and regression analysis was performed on the subgroup
of adult patients with a bystander-witnessed event of presumed cardiac aetiology
and an initial shockable rhythm (Utstein group). RESULTS: 3701 EMS-treated OHCAs
were recorded for the study period (1 January 2012-31 December 2013). Incidence
was 39/100 000 population/year. In the Utstein group (n=577), compared with the
overall group, there was a higher proportion of male patients, public event
location, bystander cardiopulmonary resuscitation (CPR) and early defibrillation.
Median EMS call-response interval was similar in both groups. A higher proportion
of patients in the Utstein group achieved return of spontaneous circulation (35%
vs 17%) and survival to hospital discharge (22% vs 6%). After multivariate
adjustment for the Utstein group, the following variables were found to be
independent predictors of the outcome survival to hospital discharge: public
event location (OR 3.1 (95% CI 1.9 to 5.0)); bystander CPR (2.4 (95% CI 1.2 to
4.9)); EMS response of 8 min or less (2.2 (95% CI 1.3 to 3.6)). CONCLUSIONS: This
study highlights the role of nationwide registries in quantifying, monitoring and
benchmarking OHCA incidence and outcome, providing baseline data upon which
service improvement effects can be measured.
PMID- 27485263
TI - Structure-antiproliferative activity studies on l-proline- and homoproline-4-N
pyrrolidine-3-thiosemicarbazone hybrids and their nickel(ii), palladium(ii) and
copper(ii) complexes.
AB - Two water-soluble thiosemicarbazone-proline (H2L(1)) and thiosemicarbazone
homoproline hybrids (H2L(2)) were synthesised. By reaction of H2L(1) with
NiCl2.6H2O, PdCl2 and CuCl2.2H2O in ethanol, the series of square-planar
complexes [Ni(H2L(1))Cl]Cl.1.3H2O (1.1.3H2O), [Pd(H2L(1))Cl]Cl.H2O (2.H2O) and
[Cu(H2L(1))Cl]Cl.0.7H2O (3.0.7H2O) was prepared, and starting from H2L(2) and
CuCl2.2H2O in methanol, the complex [Cu(H2L(2))Cl2].H2O (4.H2O) was obtained. The
compounds have been characterised by elemental analysis, spectroscopic methods
(IR, UV-vis and NMR spectroscopy), ESI mass spectrometry and single crystal X-ray
crystallography (H2L(1), 1, 2 and 4). As a solid, 1 is diamagnetic, while it is
paramagnetic in methanolic solution. The effective magnetic moment of 3.26 B.M.
at room temperature indicates the change in coordination geometry from square
planar to octahedral upon dissolution. The in vitro anticancer potency of ligand
precursors H2L(1) and H2L(2) and metal complexes 1-4 was studied in three human
cancer cell lines (A549, CH1 and SW480) and in noncancerous murine embryonal
fibroblasts (NIH/3T3), and the mechanism of cell death was also assayed by flow
cytometry. Clear-cut structure-activity relationships have been established. The
metal ions exert marked effects in a divergent manner: copper(ii) increases,
whereas nickel(ii) and palladium(ii) decrease the cytotoxicity of the hybrids.
The antiproliferative activity of H2L(1) and metal complexes 1-3 decreases in all
three tumour cell lines in the following rank order: 3 > H2L(1) > 1 > 2. The role
of square-planar geometry in the underlying mechanism of cytotoxicity of the
metal complexes studied seems to be negligible, while structural modifications at
the terminal amino group of thiosemicarbazide and proline moieties are
significant for enhancing the antiproliferative activity of both hybrids and
copper(ii) complexes.
PMID- 27485265
TI - Ethnobotanical study of wild edible plants in Burji District, Segan Area Zone of
Southern Nations, Nationalities and Peoples Region (SNNPR), Ethiopia.
AB - BACKGROUND: An ethnobotanical study of wild edible plants was conducted in Burji
District, Segan Area Zone of Southern Nations, Nationalities and Peoples Region,
Ethiopia. The objective of the study was to identify and document wild edible
plants and the associated ethnobotanical knowledge of the local people. METHODS:
Relevant ethnobotanical data focused on wild edible plants were collected using
guided field walk, semi-structured interview, and direct field observation.
Informant consensus method and group discussion were conducted for crosschecking
and verification of the information. Both descriptive statistics and quantitative
ethnobotanical methods were used for data analysis. RESULTS: We documented 46
species distributed in 37 genera and 29 families based on local claims of use as
food. Local users collect most of these plants from the wild. The common plant
families that encompass more number of wild edible plant species were
Anacardiaceae (five species) followed by Boraginaceae, Fabaceae and Solanaceae
which contributed three species each. CONCLUSION: The study showed the existence
of a number of wild edible plants which mitigate food insecurity situations
during problematic times that the people of the area face occasionally.
Informants stated that wild growing edible plants are under threat due to
increased anthropogenic pressure and disturbed climatic conditions. This calls
for urgent and collaborative actions to keep the balance between edible plants
availability in the wild and their utilization by the community. Furthermore, the
study attempted to prioritize very important wild edible plants as perceived by
the local people for possible domestication and/or sustainable utilization.
PMID- 27485264
TI - Fiberless multicolor neural optoelectrode for in vivo circuit analysis.
AB - Maximizing the potential of optogenetic approaches in deep brain structures of
intact animals requires optical manipulation of neurons at high spatial and
temporal resolutions, while simultaneously recording electrical data from those
neurons. Here, we present the first fiber-less optoelectrode with a
monolithically integrated optical waveguide mixer that can deliver multicolor
light at a common waveguide port to achieve multicolor modulation of the same
neuronal population in vivo. We demonstrate successful device implementation by
achieving efficient coupling between a side-emitting injection laser diode (ILD)
and a dielectric optical waveguide mixer via a gradient-index (GRIN) lens. The
use of GRIN lenses attains several design features, including high optical
coupling and thermal isolation between ILDs and waveguides. We validated the
packaged devices in the intact brain of anesthetized mice co-expressing
Channelrhodopsin-2 and Archaerhodopsin in pyramidal cells in the hippocampal CA1
region, achieving high quality recording, activation and silencing of the exact
same neurons in a given local region. This fully-integrated approach demonstrates
the spatial precision and scalability needed to enable independent activation and
silencing of the same or different groups of neurons in dense brain regions while
simultaneously recording from them, thus considerably advancing the capabilities
of currently available optogenetic toolsets.
PMID- 27485266
TI - Lymphatic Leak Occurring After Surgical Lymph Node Dissection: A Preliminary
Study Assessing the Feasibility and Outcome of Lymphatic Embolization.
AB - PURPOSE: To analyze imaging findings of lymphatic leakage associated with
surgical lymph node dissection on lymphangiography and assess the outcome of
lymphatic embolization. MATERIALS AND METHODS: This retrospective study comprised
21 consecutive patients who were referred for lymphatic intervention between
March 2014 and April 2015 due to postsurgical lymphatic leaks. Lymphangiography
was performed through inguinal lymph nodes to identify the leak. When a leak was
found, lymphatic embolization was performed by fine-needle injection of N-butyl
cyanoacrylate into the site of leakage or into an inflow lymphatic vessel or into
a pelvic lymph node located below the leakage. Electronic medical records and
imaging studies were reviewed to assess the outcome. RESULT: Lymphangiography
revealed single or multiple leaks in all but one patient. Lymphatic embolization
was performed in 20 patients with leaks. Including the patient who did not
undergo embolization, 17 patients (81.0 %) showed initial response to treatment.
Three patients underwent repeated embolization with successful results. The
overall success rate was 95.2 %. The mean duration of hospitalization after
lymphatic intervention was 5.9 days. During a mean follow-up period of 11 months,
two patients developed localized swelling in the groin following lipiodol
injection. There were no complications related to lymphatic embolization. Three
patients were found to have developed small, asymptomatic lymphoceles on CT or
MRI that did not require further treatment. CONCLUSION: Lymphangiography is
useful for detecting lymphatic leakage occurring after lymph node dissection.
Furthermore, lymphatic embolization is feasible, effective, and safe for managing
leaks demonstrated on lymphangiography.
PMID- 27485267
TI - Transperineal Prostate Core Needle Biopsy: A Comparison of Coaxial Versus
Noncoaxial Method in a Randomised Trial.
AB - PURPOSE: To compare the procedural time and complication rate of coaxial
technique with those of noncoaxial technique in transperineal prostate biopsy.
MATERIALS AND METHODS: Transperineal prostate biopsy with coaxial (first group, n
= 120) and noncoaxial (second group, n = 120) methods was performed randomly in
240 patients. The procedural time was recorded. The level of pain experienced
during the procedure was assessed on a visual analogue scale (VAS), and the rate
of complications was evaluated in comparison of the two methods. RESULTS: The
procedural time was significantly shorter in the first group (p < 0.001). In the
first group, pain occurred less frequently (p = 0.002), with a significantly
lower VAS score being experienced (p < 0.002). No patient had post procedural
fever. Haematuria (p = 0.029) and haemorrhage from the site of biopsy (p < 0.001)
were seen less frequently in the first group. There was no significant difference
in the rate of urethral haemorrhage between the two groups (p = 0.059). Urinary
retention occurred less commonly in the first group (p = 0.029). No significant
difference was seen in the rate of dysuria between the two groups (p = 0.078).
CONCLUSIONS: Transperineal prostate biopsy using a coaxial needle is a faster and
less painful method with a lower rate of complications compared with conventional
noncoaxial technique.
PMID- 27485268
TI - Quantitative Real-Time Fluoroscopy Analysis on Measurement of the Hepatic
Arterial Flow During Transcatheter Arterial Chemoembolization of Hepatocellular
Carcinoma: Comparison with Quantitative Digital Subtraction Angiography Analysis.
AB - PURPOSE: To quantify the arterial flow change during transcatheter arterial
chemoembolization (TACE) for hepatocellular carcinoma (HCC) using digital
subtraction angiography, quantitative color-coding analysis (d-QCA), and real
time subtraction fluoroscopy QCA (f-QCA). MATERIALS AND METHODS: This prospective
study enrolled 20 consecutive patients with HCC who had undergone TACE via a
subsegmental approach between February 2014 and April 2015. The TACE endpoint was
a sluggish antegrade tumor-feeding arterial flow. d-QCA and f-QCA were used for
determining the relative maximal density time (rTmax) of the selected arteries.
The rTmax of the selected arteries was analyzed in d-QCA and f-QCA before and
after TACE, and its correlation in both analyses was evaluated. RESULTS: The pre-
and post-TACE rTmax of the embolized segmental artery in d-QCA and f-QCA were
1.59 +/- 0.81 and 2.97 +/- 1.80 s (P < 0.001) and 1.44 +/- 0.52 and 2.28 +/- 1.02
s (P < 0.01), respectively. The rTmax of the proximal hepatic artery did not
significantly change during TACE in d-QCA and f-QCA. The Spearman correlation
coefficients of the pre- and post-TACE rTmax of the embolized segmental artery
between d-QCA and f-QCA were 0.46 (P < 0.05) and 0.80 (P < 0.001). Radiation
doses in one series of d-QCA and f-QCA were 140.7 +/- 51.5 milligray (mGy) and
2.5 +/- 0.7 mGy, respectively. CONCLUSIONS: f-QCA can quantify arterial flow
changes with a higher temporal resolution and lower radiation dose. Flow
quantification of the embolized segmental artery using f-QCA and d-QCA is highly
correlated.
PMID- 27485269
TI - Amine coupling versus biotin capture for the assessment of sulfonamide as ligands
of hCA isoforms.
AB - This work was dedicated to the development of a reliable SPR method allowing the
simultaneous and quick determination of the affinity and selectivity of designed
sulfonamide derivatives for hCAIX and hCAXII versus hCAII, in order to provide an
efficient tool to discover drugs for anticancer therapy of solid tumors. We
performed for the first time a comparison of two immobilization approaches of hCA
isoforms. First one relies on the use of an amine coupling strategy, using a CM7
chip to obtain higher immobilization levels than with a CM5 chip and consequently
the affinity with an higher precision (CV% < 10%). The second corresponds to a
capture of proteins on a streptavidin chip, named CAP chip, after optimization of
biotinylation conditions (amine versus carboxyl coupling, biotin to protein
ratio). Thanks to the amine coupling approach, only hCAII and hCAXII isoforms
were efficiently biotinylated to reach relevant immobilization (3000 RU and 2700
RU, respectively) to perform affinity studies. For hCAIX, despite a successful
biotinylation, capture on the CAP chip was a failure. Finally, concordance
between affinities obtained for the three derivatives to CAs isozymes on both
chips has allowed to valid the approaches for a further screening of new
derivatives.
PMID- 27485270
TI - Development of a scintillation proximity binding assay for high-throughput
screening of hematopoietic prostaglandin D2 synthase.
AB - Prostaglandin D2 synthase (PGDS) catalyzes the isomerization of prostaglandin H2
(PGH2) to prostaglandin D2 (PGD2). PGD2 produced by hematopoietic prostaglandin
D2 synthase (H-PGDS) in mast cells and Th2 cells is proposed to be a mediator of
allergic and inflammatory responses. Consequently, inhibitors of H-PGDS represent
potential therapeutic agents for the treatment of inflammatory diseases such as
asthma. Due to the instability of the PGDS substrate PGH2, an in-vitro enzymatic
assay is not feasible for large-scale screening of H-PGDS inhibitors. Herein, we
report the development of a competition binding assay amenable to high-throughput
screening (HTS) in a scintillation proximity assay (SPA) format. This assay was
used to screen an in-house compound library of approximately 280,000 compounds
for novel H-PGDS inhibitors. The hit rate of the H-PGDS primary screen was found
to be 4%. This high hit rate suggests that the active site of H-PGDS can
accommodate a large diversity of chemical scaffolds. For hit prioritization,
these initial hits were rescreened at a lower concentration in SPA and tested in
the LAD2 cell assay. 116 compounds were active in both assays with IC50s ranging
from 6 to 807 nM in SPA and 82 nM to 10 MUM in the LAD2 cell assay.
PMID- 27485271
TI - Type-specific photoreceptor loss in pigeons after disruption of parasympathetic
control of choroidal blood flow by the medial subdivision of the nucleus of
Edinger-Westphal.
AB - The medial part of the nucleus of Edinger-Westphal (EWM) in birds mediates light
regulated adaptive increases in choroidal blood flow (ChBF). We sought to
characterize the effect of loss of EWM-mediated ChBF regulation on photoreceptor
health in pigeons housed in either moderate intensity diurnal or constant light
(CL). Photoreceptor abundance following complete EWM destruction was compared to
that following a lesion in the pupil control circuit (as a control for spread of
EWM lesions to the nearby pupil-controlling lateral EW) or following no EW
damage. Birds were housed post-lesion in a 12 h 400 lux light/12 h dark light
cycle for up to 16.5 months, or in constant 400 lux light for up to 3 weeks.
Paraformaldehyde-glutaraldehyde fixed eyes were embedded in plastic, sectioned,
slide-mounted, and stained with toluidine blue/azure II. Blinded analysis of
photoreceptor outer segment abundance was performed, with outer segment types
distinguished by oil droplet tint and laminar position. Brains were examined
histologically to assess lesion accuracy. Disruption of pupil control had no
adverse effect on photoreceptor outer segment abundance in either diurnal light
or CL, but EWM destruction led to 50-60% loss of blue/violet cone outer segments
in both light conditions, and a 42% loss of principal cone outer segments in CL.
The findings indicate that adaptive regulation of ChBF by the EWM circuit plays a
role in maintaining photoreceptor health and mitigates the harmful effect of
light on photoreceptors, especially short wavelength-sensitive cone
photoreceptors.
PMID- 27485272
TI - Antioxidant status of serum bilirubin and uric acid in patients with polymyositis
and dermatomyositis.
AB - OBJECTIVE: Oxidative stress and variations in antioxidant status are implicated
in the pathogenesis of inflammatory and autoimmune diseases. Polymyositis and
dermatomyositis (PM/DM) are autoimmune diseases with inflammatory cells
infiltrating into skeletal muscles, and the antioxidant status is still
controversial. The aim of our study was to investigate the correlation between
PM/DM and the antioxidant status of serum bilirubin (Tbil, Dbil and Ibil) and
uric acid (UA). MATERIALS AND METHODS: We measured serum concentrations of
bilirubin (Tbil, Dbil and Ibil) and uric acid in 384 individuals, including 110
PM/DM patients and 274 healthy controls. RESULTS: We found that PM/DM patients
had significantly lower serum concentrations of bilirubin (Tbil and Ibil) and
uric acid than healthy controls, whether male or female. Also, after separately
adjusting the covariances of age and gender, Tbil, Dbil, Ibil and UA were all
relevant factors for PM/DM. Moreover, there were no significant differences in
serum antioxidant molecule levels between PM and DM subgroups. CONCLUSION: Our
study demonstrated the low serum levels of bilirubin and uric acid in patients
with PM/DM. This suggested low antioxidant status in PM/DM patients with
excessive oxidative stress.
PMID- 27485275
TI - Dissociative trance and spirit possession: Challenges for cultures in transition.
AB - The cross-cultural validity of dissociative possession and trance disorders is a
matter of some debate, limiting research and meaningful interpretation of
prevalence data. Intimate to these concerns is the status of spirit possession
categories studied in the social sciences, particularly anthropology. These two
categories are phenomenologically related and display similar epidemiological
associations. In India, dissociative and conversion disorders are fairly common
in clinical settings. There is no doubt that there are true cultural variations
in possession and trance disorders. A new framework may enable clinicians to
better understand possession states and spirit possession.
PMID- 27485274
TI - Population genomics reveals multiple drivers of population differentiation in a
sex-role-reversed pipefish.
AB - A major goal of molecular ecology is to identify the causes of genetic and
phenotypic differentiation among populations. Population genomics is suitably
poised to tackle these key questions by diagnosing the evolutionary mechanisms
driving divergence in nature. Here, we set out to investigate the evolutionary
processes underlying population differentiation in the Gulf pipefish, Syngnathus
scovelli. We sampled approximately 50 fish from each of 12 populations
distributed from the Gulf coast of Texas to the Atlantic coast of Florida and
performed restriction-site-associated DNA sequencing to identify SNPs throughout
the genome. After imposing quality and stringency filters, we selected a panel of
6348 SNPs present in all 12 populations, 1753 of which were not physically
linked. We identified a genome-wide pattern of isolation by distance, in addition
to a more substantial genetic break separating populations in the Gulf of Mexico
from those in the Atlantic. We also used several divergence outlier approaches
and tests for genotype-environment correlations to identify 400 SNPs putatively
involved in local adaptation. Patterns of phenotypic differentiation and
variation diverged from the overall genomic pattern, suggesting that selection,
phenotypic plasticity or demographic factors may be shaping phenotypes in
distinct populations. Overall, our results suggest that population divergence is
driven by a variety of factors in S. scovelli, including neutral processes and
selection on multiple traits.
PMID- 27485273
TI - Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter
methylation and global DNA hypomethylation in type I and type II ovarian cancers.
AB - BACKGROUND: In this retrospective study we evaluated the respective correlations
and clinical relevance of FOLR1 mRNA expression, FOLR1 promoter specific
methylation and global DNA hypomethylation in type I and type II ovarian cancer.
METHODS: Two hundred fifty four ovarian cancers, 13 borderline tumours and 60
samples of healthy fallopian epithelium and normal ovarian epithelium were
retrospectively analysed for FOLR1 expression with RT-PCR. FOLR1 DNA promoter
methylation and global DNA hypomethylation (measured by means of LINE1 DNA
hypomethylation) were evaluated with MethyLight technique. RESULTS: No
correlation between FOLR1 mRNA expression and its specific promoter DNA
methylation was found neither in type I nor in type II cancers, however, high
FOLR1 mRNA expression was found to be correlated with global DNA hypomethylation
in type II cancers (p = 0.033). Strong FOLR1 mRNA expression was revealed for
Grades 2-3, FIGO stages III-IV, residual disease > 0, and serous histotype. High
FOLR1 expression was found to predict increased platinum sensitivity in type I
cancers (odds ratio = 3.288; 1.256-10.75; p = 0.020). One-year survival analysis
showed in type I cancers an independent better outcome for strong expression of
FOLR1 in FIGO stage III and IV. For the entire follow up period no significant
independent outcome for FOLR1 expression was revealed. In type I cancers LINE 1
DNA hypomethylation was found to exhibit a worse PFS and OS which were confirmed
to be independent in multivariate COX regression model for both PFS (p = 0.026)
and OS (p = 0.012). CONCLUSION: No correlations were found between FOLR1
expression and its specific promoter methylation, however, high FOLR1 mRNA
expression was associated with DNA hypomethylation in type II cancers. FOLR1 mRNA
expression did not prove to predict clinical outcome in type II cancers, although
strong FOLR1 expression generally denotes ovarian cancers with highly aggressive
phenotype. In type I cancers, however, strong FOLR1 expression has been found to
be a reliable indicator of improved platinum responsiveness reflecting a
transient better one-year follow up outcome in highly FOLR1 expressing type I
cancers. An independent prognostic role of global DNA hypomethylation was
demonstrated in type I tumours.
PMID- 27485276
TI - Coke Formation in a Zeolite Crystal During the Methanol-to-Hydrocarbons Reaction
as Studied with Atom Probe Tomography.
AB - Understanding the formation of carbon deposits in zeolites is vital to developing
new, superior materials for various applications, including oil and gas
conversion processes. Herein, atom probe tomography (APT) has been used to
spatially resolve the 3D compositional changes at the sub-nm length scale in a
single zeolite ZSM-5 crystal, which has been partially deactivated by the
methanol-to-hydrocarbons reaction using (13) C-labeled methanol. The results
reveal the formation of coke in agglomerates that span length scales from tens of
nanometers to atomic clusters with a median size of 30-60 (13) C atoms. These
clusters correlate with local increases in Bronsted acid site density,
demonstrating that the formation of the first deactivating coke precursor
molecules occurs in nanoscopic regions enriched in aluminum. This nanoscale
correlation underscores the importance of carefully engineering materials to
suppress detrimental coke formation.
PMID- 27485277
TI - Controversies in Veterinary Nephrology: Renal Diets Are Indicated for Cats with
International Renal Interest Society Chronic Kidney Disease Stages 2 to 4: The
Pro View.
AB - Renal diets have been the mainstay of therapy for cats with chronic kidney
disease (CKD) for many decades. Clinical trials in cats with CKD have shown them
to be effective in improving survival, reducing uremic crises, and improving
serum urea nitrogen and phosphorous concentrations. It has shown that, when food
intake is adequate, renal diets can maintain body weight and body condition
scores for up to 2 years. Although some have questioned whether renal diets
provide adequate protein and have advocated feeding higher-protein diets to cats
with CKD, there is currently no convincing evidence in support of this proposal.
PMID- 27485278
TI - Management of Proteinuria in Dogs and Cats with Chronic Kidney Disease.
AB - Proteinuria is a negative prognostic indicator for dogs and cats with chronic
kidney disease. A normal dog or cat should excrete very little protein and have a
urine protein:creatinine ratio that is less than 0.4 or less than 0.2,
respectively; persistent proteinuria above this magnitude warrants attention.
Administration of angiotensin converting enzyme inhibitors and/or angiotensin
receptor blockers, blood pressure control and nutritional modification are
considered a standard of care for renal proteinuria. Renal biopsy and
administration of immunosuppressive agents should be considered in animals with
glomerular proteinuria that have not responded to standard therapy. Targeted
patient monitoring is essential when instituting management of proteinuria.
PMID- 27485279
TI - Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury:
The Role of Novel Biomarkers as Early and Accurate Diagnostics.
AB - Chronic kidney disease (CKD) and acute kidney injury (AKI) are interconnected and
the presence of one is a risk for the other. CKD is an important predictor of AKI
after exposure to nephrotoxic drugs or major surgery, whereas persistent or
repetitive injury could result in the progression of CKD. This brings new
perspectives to the diagnosis and monitoring of kidney diseases highlighting the
need for a panel of kidney-specific biomarkers that reflect functional as well as
structural damage and recovery, predict potential risk and provide prognosis.
This article discusses the kidney-specific biomarkers, symmetric dimethylarginine
(SDMA), clusterin, cystatin B, and inosine.
PMID- 27485280
TI - Protective effects of ghrelin against oxidative stress, inducible nitric oxide
synthase and inflammation in a mouse model of myocardial ischemia/reperfusion
injury via the HMGB1 and TLR4/NF-kappaB pathway.
AB - The present study aimed to investigate the protective effects of ghrelin against
oxidative stress, inducible nitric oxide synthase (iNOS) and inflammation in a
mouse model of myocardial ischemia/reperfusion injury (MIRI). In addition, the
study aimed to determine its underlying mechanisms. A mouse model of MIRI was
used in vivo, in order to ascertain the protective effects of ghrelin on MIRI.
Commercial kits were used to measure the serum levels of creatine kinase (CK) and
lactate dehydrogenase (LDH) in MIRI mice. Furthermore, Evan's Blue
triphenyltetrazolium chloride solution was used to analyze the protective effects
of ghrelin against infarct size in MIRI mice. The underlying mechanisms were
determined by measuring MIRI-induced tumor necrosis factor (TNF)-alpha,
interleukin (IL)-6, superoxide dismutase (SOD), glutathione (GSH), GSH-peroxidase
(GSH-PX), malondialdehyde (MDA) and caspase-3/caspase-9 activities, and iNOS,
high mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4) and nuclear factor
(NF)-kappaB protein expression in MIRI mice. The results demonstrated that MIRI
led to an increase in infarct size; CK, LDH, TNF-alpha, IL-6, MDA, caspase-3 and
caspase-9 serum levels; and iNOS protein expression. MIRI resulted in inhibition
of SOD, FSH and GSH-PX levels. Conversely, these alterations were significantly
inhibited following treatment with ghrelin. In addition, the protective effects
of ghrelin against MIRI suppressed HMGB1, TLR4 and NF-kappaB protein expression
in MIRI mice. The present study revealed that ghrelin exerted protective effects
against oxidative stress, iNOS and inflammation in MIRI mice via the
HMGB1/TLR4/NF-kappaB pathway.
PMID- 27485281
TI - Distribution of tetracycline resistance genes in anaerobic treatment of waste
sludge: The role of pH in regulating tetracycline resistant bacteria and
horizontal gene transfer.
AB - Although pH value has been widely regarded as an important factor that affects
resource recovery of waste sludge, the potential influence of diverse pHs on the
distribution of tetracycline resistance genes (TRGs) during sludge anaerobic
treatment is largely unknown. Here we reported that in the range of pH 4-10, 0.58
1.18 log unit increase of target TRGs was observed at pH 4, compared with that at
pH 7, while 0.70-1.31 log unit further removal were obtained at pH 10. Mechanism
study revealed that varied pHs not only altered the community structures of
tetracycline resistant bacteria (TRB), but also changed their relative
abundances, benefitting the propagation (acidic pHs) or attenuation (alkaline
pHs) of TRB. Further investigation indicated that the amount and gene-possessing
abilities of key genetic vectors for horizontal TRGs transfer were greatly
promoted at acidic pHs but restricted under alkaline conditions.
PMID- 27485282
TI - Glucose supplementation-induced changes in the Auxenochlorella protothecoides
fatty acid composition suitable for biodiesel production.
AB - This study evaluates the effect of different concentrations of glucose
supplementation on growth, lipid accumulation, and the fatty acid profile in the
Auxenochlorella protothecoides. Addition of glucose promoted the growth rate and
decreased the chlorophyll content. Compared with photoautotrophic cells, an
increase in the lipid content was observed in mixotrophic cells. The glucose
addition induced changes in the fatty acid profile. Higher content of saturated
fatty acids was found in the case of cells growing in the glucose-free medium.
Oleic acid was the predominant component in mixotrophic cells supplemented with
5gL(-1) glucose, while linoleic acids dominated in cultures supplemented with
both 1 and 3gL(-1) glucose. The use of glucose was associated with decreased
levels of linolenic acid and PUFA. The changes in the fatty acid profile in
mixotrophic cells are favourable for biodiesel production.
PMID- 27485283
TI - Ion mobility spectrometry-mass spectrometry examination of the structures,
stabilities, and extents of hydration of dimethylamine-sulfuric acid clusters.
AB - We applied an atmospheric pressure differential mobility analyzer (DMA) coupled
to a time-of-flight mass spectrometer to examine the stability, mass-mobility
relationship, and extent of hydration of dimethylamine-sulfuric acid cluster
ions, which are of relevance to nucleation in ambient air. Cluster ions were
generated by electrospray ionization and were of the form:
[H((CH3)2NH)x(H2SO4)y](+) and [(HSO4)((CH3)2NH)x(H2SO4)y](-), where 4 <= x <= 8,
and 5 <= y <= 12. Under dry conditions, we find that positively charged cluster
ions dissociated via loss of both multiple dimethylamine and sulfuric acid
molecules after mobility analysis but prior to mass analysis, and few parent ions
were detected in the mass spectrometer. Dissociation also occurred for negative
ions, but to a lesser extent than for positive ions for the same mass
spectrometer inlet conditions. Under humidified conditions (relative humidities
up to 30% in the DMA), positively charged cluster ion dissociation in the mass
spectrometer inlet was mitigated and occurred primarily by H2SO4 loss from ions
containing excess acid molecules. DMA measurements were used to infer collision
cross sections (CCSs) for all identifiable cluster ions. Stokes-Millikan equation
and diffuse/inelastic gas molecule scattering predicted CCSs overestimate
measured CCSs by more than 15%, while elastic-specular collision model
predictions are in good agreement with measurements. Finally, cluster ion
hydration was examined by monitoring changes in CCSs with increasing relative
humidity. All examined cluster ions showed a modest amount of water molecule
adsorption, with percentage increases in CCS smaller than 10%. The extent of
hydration correlates directly with cluster ion acidity for positive ions.
PMID- 27485284
TI - Long-Term, Prospective Performance of the MD Anderson Dysphagia Inventory in "Low
Intermediate Risk" Oropharyngeal Carcinoma After Intensity Modulated Radiation
Therapy.
AB - PURPOSE: To characterize long-term MD Anderson Dysphagia Inventory (MDADI)
results after primary intensity modulated radiation therapy (IMRT) for
oropharyngeal carcinoma (OPC) among patients with "low-intermediate risk" OPC who
would be eligible for current trials (eg, ECOG 3311, NRG HN002, CRUK PATHOS).
METHODS AND MATERIALS: A retrospective pooled analysis combined data from 3
single-institution clinical trials for advanced-stage head and neck carcinoma.
Inclusion criteria were clinical stage III/IV OPC (T1-2/N1-2b, T3/N0-2b) treated
with definitive split-field IMRT and prospectively collected MDADI at baseline
and at least 1 posttreatment interval available in trial databases. Patients were
sampled to represent likely human papillomavirus (HPV)-associated disease
(HPV+/p16+ or <10 pack-years if HPV/p16 unknown). The MDADI composite scores were
collected at baseline and 6, 12, and 24 months after treatment. Pairwise tests
were Bonferroni corrected for multiple comparisons. RESULTS: Forty-six patients
were included. All received bilateral neck irradiation with a median dose of 70
Gy and systemic therapy (57% concurrent, 43% induction only). Overall the mean
baseline MDADI composite score was 90.1, dropping to 74.6 at 6 months (P<.0001)
and rising to 78.5 (P<.0001) and 83.1 (P=.002) by 12 and 24 months relative to
baseline, respectively, representing a clinically meaningful drop in MDADI scores
at 6 months that partially recovers by 24 months (6 vs 24 months, P=.05). Poor
MDADI scores (composite <60) were reported in 4%, 11%, 15%, and 9% of patients at
baseline and 6, 12, and 24 months, respectively. Fifteen percent of patients had
a persistently depressed composite score by at least 20 points at the 24-month
interval. CONCLUSION: "Low-intermediate risk" patients with OPC treated with
laryngeal/esophageal inlet dose-optimized split-field IMRT are highly likely to
report recovery of acceptable swallowing function in long-term follow-up. Only
15% report poor swallowing function and/or persistently depressed MDADI at 12
months or more after IMRT. These data serve as a benchmark future trial design
and endpoint interpretation.
PMID- 27485286
TI - MCM2-7 conformational changes in the presence of DNA.
PMID- 27485285
TI - Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a
Data Dependent Acquisition and SWATH-MS Combined Workflow.
AB - PURPOSE: Early and accurate assessment of radiation injury by radiation
responsive biomarkers is critical for triage and early intervention. Biofluids
such as urine and serum are convenient for such analysis. Recent research has
also suggested that exosomes are a reliable source of biomarkers in disease
progression. In the present study, we analyzed total urine proteome and exosomes
isolated from urine or serum for potential biomarkers of acute and persistent
radiation injury in mice exposed to lethal whole body irradiation (WBI). METHODS
AND MATERIALS: For feasibility studies, the mice were irradiated at 10.4 Gy WBI,
and urine and serum samples were collected 24 and 72 hours after irradiation.
Exosomes were isolated and analyzed using liquid chromatography mass
spectrometry/mass spectrometry-based workflow for radiation exposure signatures.
A data dependent acquisition and SWATH-MS combined workflow approach was used to
identify significantly exosome biomarkers indicative of acute or persistent
radiation-induced responses. For the validation studies, mice were exposed to 3,
6, 8, or 10 Gy WBI, and samples were analyzed for comparison. RESULTS: A
comparison between total urine proteomics and urine exosome proteomics
demonstrated that exosome proteomic analysis was superior in identifying
radiation signatures. Feasibility studies identified 23 biomarkers from urine and
24 biomarkers from serum exosomes after WBI. Urinary exosome signatures
identified different physiological parameters than the ones obtained in serum
exosomes. Exosome signatures from urine indicated injury to the liver,
gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular
injuries and acute inflammation in response to radiation. Selected urinary
exosomal biomarkers also showed changes at lower radiation doses in validation
studies. CONCLUSIONS: Exosome proteomics revealed radiation- and time-dependent
protein signatures after WBI. A total of 47 differentially secreted proteins were
identified in urinary and serum exosomes. Together, these data showed the
feasibility of defining biomarkers that could elucidate tissue-associated and
systemic response caused by high-dose ionizing radiation. This is the first
report using an exosome proteomics approach to identify radiation signatures.
PMID- 27485288
TI - Effect of gear ratio on peak power and time to peak power in BMX cyclists.
AB - The aim of this study was to ascertain if gear ratio selection would have an
effect on peak power and time to peak power production in elite Bicycle Motocross
(BMX) cyclists. Eight male elite BMX riders volunteered for the study. Each rider
performed three, 10-s maximal sprints on an Olympic standard indoor BMX track.
The riders' bicycles were fitted with a portable SRM power meter. Each rider
performed the three sprints using gear ratios of 41/16, 43/16 and 45/16 tooth.
The results from the 41/16 and 45/16 gear ratios were compared to the current
standard 43/16 gear ratio. Statistically, significant differences were found
between the gear ratios for peak power (F(2,14) = 6.448; p = .010) and peak
torque (F(2,14) = 4.777; p = .026), but no significant difference was found for
time to peak power (F(2,14) = 0.200; p = .821). When comparing gear ratios, the
results showed a 45/16 gear ratio elicited the highest peak power,1658 +/- 221 W,
compared to 1436 +/- 129 W and 1380 +/- 56 W, for the 43/16 and 41/16 ratios,
respectively. The time to peak power showed a 41/16 tooth gear ratio attained
peak power in -0.01 s and a 45/16 in 0.22 s compared to the 43/16. The findings
of this study suggest that gear ratio choice has a significant effect on peak
power production, though time to peak power output is not significantly affected.
Therefore, selecting a higher gear ratio results in riders attaining higher power
outputs without reducing their start time.
PMID- 27485287
TI - Colorectal cancer in southern Israel: Comparison between Bedouin Arab and Jewish
patients.
AB - PURPOSE: Colorectal cancer (CRC) is the second most common malignancy and the
third leading cause of cancer deaths in Israel; it is less common among the Arab
than the Jewish population. This study compares the clinico-pathologic features,
treatment, and prognosis between Bedouin-Arab (BA) and Jewish CRC patients
treated at our medical centre. METHODS: The medical records of 56 BA patients
with CRC were compared retrospectively to 115 Jewish patients. Collected data
included age, gender, history of smoking, family history of cancer, presenting
symptoms, laboratory tests, previous malignancy, tumor characteristics, surgery
type, stoma formation and closure, types of adjuvant treatment, and outcome.
RESULTS: BA patients were younger (mean age 68 versus 57 years, p < 0.001),
showed a higher incidence in females (p = 0.045), and had a lower frequency of a
family history of cancer (p = 0.005) compared to Jewish patients. BA patients had
a higher presentation of rectal bleeding and a lower rate of anemia at tumor
diagnosis (p = 0.05 and p = 0.004, respectively) with a more distal location of
the tumor (p = 0.003). BA patients more often received chemotherapy and
radiotherapy (p = 0.02 and p = 0.04, respectively). Disease-free survival was
shorter among BA patients (p = 0.023); overall survival was similar in both
groups. CONCLUSIONS: CRC in BAs is characterized by a higher proportion of
female, younger age, and higher proportion of distal location compared to Jewish
patients. These differences in biology may be related to differences in past
lifestyles and diet of BA compared to Jewish patients, and are expected to
decrease in the following years as the BA population continues to undergo
"westernization" changes.
PMID- 27485289
TI - Isotopic Composition of Atmospheric Mercury in China: New Evidence for Sources
and Transformation Processes in Air and in Vegetation.
AB - The isotopic composition of atmospheric total gaseous mercury (TGM) and particle
bound mercury (PBM) and mercury (Hg) in litterfall samples have been determined
at urban/industrialized and rural sites distributed over mainland China for
identifying Hg sources and transformation processes. TGM and PBM near
anthropogenic emission sources display negative delta(202)Hg and near-zero
Delta(199)Hg in contrast to relatively positive delta(202)Hg and negative
Delta(199)Hg observed in remote regions, suggesting that different sources and
atmospheric processes force the mass-dependent fractionation (MDF) and mass
independent fractionation (MIF) in the air samples. Both MDF and MIF occur during
the uptake of atmospheric Hg by plants, resulting in negative delta(202)Hg and
Delta(199)Hg observed in litter-bound Hg. The linear regression resulting from
the scatter plot relating the delta(202)Hg to Delta(199)Hg data in the TGM
samples indicates distinct anthropogenic or natural influences at the three study
sites. A similar trend was also observed for Hg accumulated in broadleaved
deciduous forest foliage grown in areas influenced by anthropogenic emissions.
The relatively negative MIF in litter-bound Hg compared to TGM is likely a result
of the photochemical reactions of Hg(2+) in foliage. This study demonstrates the
diagnostic stable Hg isotopic composition characteristics for separating
atmospheric Hg of different source origins in China and provides the isotopic
fractionation clues for the study of Hg bioaccumulation.
PMID- 27485290
TI - Tiron ameliorates oxidative stress and inflammation in a murine model of airway
remodeling.
AB - Airway remodeling includes lung structural changes that have a role in the
irreversibility of pulmonary dysfunction shown in chronic bronchial asthmatics.
The current experiment investigated the effect of the mitochondrial antioxidant,
tiron in comparison with dexamethasone (DEXA) on airway remodeling in chronic
asthma. Sensitized BALB/c mice were challenged with ovalbumin (OVA) aerosol for
8weeks, OVA sensitized-challenged mice were treated with either DEXA or tiron,
respectively. After that, lung tissue and bronchoaveolar lavage fluid (BALF) were
used for measurement of different biological markers. Lungs were examined for
histopathological changes and immunohistochemistry. Upon comparing with vehicle
treated animals, trion or DEXA treatment significantly reduced eosinophils,
lymphocytes, neutrophils and macrophages count in the BALF. Both drugs
significantly alleviated chronic OVA-induced oxidative stress as illustrated by
decreased pulmonary malondialdenhyde (MDA) and increased glutathione (GSH) and
superoxide dismutase (SOD) levels. Asthmatic mice exhibited elevated levels of
NOx, IL-13 and TGF-beta1 that were reduced by DEXA and tiron. Histopathological
changes and increased immunoreactivity of nuclear factor-Kappa B (NF-kappa B) in
OVA-challenged mice were minimized by tiron and DEXA treatment. In conclusion, in
this model of chronic asthma DEXA and tiron ameliorated airway remodeling and
inflammation in experimental chronic asthma with no difference between the effect
of tiron and DEXA. Tiron has a potential role as adjuvant treatment in chronic
asthma.
PMID- 27485292
TI - Calcium-induced conformational changes of Thrombospondin-1 signature domain:
implications for vascular disease.
AB - CONTEXT: Thrombospondin1 (TSP1) participates in numerous signaling pathways
critical for vascular physiology and disease. The conserved signature domain of
thrombospondin 1 (TSP1-Sig1) comprises three epidermal growth factor (EGF), 13
calcium-binding type 3 thrombospondin (T3) repeats, and one lectin-like module
arranged in a stalk-wire-globe topology. TSP1 is known to be present in both
calcium-replete (Holo-) and calcium-depleted (Apo-) state, each with distinct
downstream signaling effects. OBJECTIVE: To prepare a homology model of TSP1-Sig1
and investigate the effect of calcium on its dynamic structure and interactions.
METHODS: A homology model of Holo-TSP1-Sig1 was prepared with TSP2 as template in
Swissmodel workspace. The Apo-form of the model was obtained by omitting the
bound calcium ions from the homology model. Molecular dynamics (MD) simulation
studies (100 ns) were performed on the Holo- and Apo- forms of TSP1 using
Gromacs4.6.5. RESULTS AND DISCUSSION: After simulation, Holo-TSP1-Sig1 showed
significant reorientation at the interface of the EGF1-2 and EGF2-3 modules. The
T3 wire is predicted to show the maximum mobility and deviation from the initial
model. In Apo-TSP1-Sig1 model, the T3 repeats unfolded and formed coils with
predicted increase in flexibility. Apo-TSP1-Sig1model also predicted the exposure
of the binding sites for neutrophil elastase, integrin and fibroblast growth
factor 2. We present a structural model and hypothesis for the role of TSP1-Sig1
interactions in the development of vascular disorders. CONCLUSION: The simulated
model of the fully calcium-loaded and calcium-depleted TSP1-Sig1 may enable the
development of its interactions as a novel therapeutic target for the treatment
of vascular diseases.
PMID- 27485291
TI - The role of the CCN family of proteins in blood cancers.
AB - Haematopoiesis is the term used to describe the production of blood cells. This
is a tightly regulated hierarchical system in which mature circulating blood
cells develop from a small population of haematopoietic stem (HSC) and progenitor
cells within the microenvironment of the bone marrow. Molecular and genetic
abnormalities arising in these stem cells lead to a block in the normal programme
of proliferation and differentiation and result in the development of the blood
cancers known as the leukaemias and lymphomas. Recently the regulatory role of
the bone marrow microenvironment or niche has also become increasingly
recognised. The interface between the bone and bone marrow (endosteum) and the
region surrounding the blood vessels (perivascular) provide distinct niches
harbouring quiescent HSC or proliferative HSC respectively. Current
chemotherapeutic regimes can often successfully target the proliferative HSC but
disease relapse occurs due to residual quiescent HSC. Understanding these
developmental and regulatory processes and the associated cell communication
mechanisms are thus crucial to the development of new treatment strategies. The
CCN family of proteins have been recognised to play a key role in all aspects of
haematopoiesis.
PMID- 27485293
TI - The Moses-Littenberg meta-analytical method generates systematic differences in
test accuracy compared to hierarchical meta-analytical models.
AB - OBJECTIVE: To compare meta-analyses of diagnostic test accuracy using the Moses
Littenberg summary receiver operating characteristic (SROC) approach with those
of the hierarchical SROC (HSROC) model. STUDY DESIGN AND SETTING: Twenty-six data
sets from existing test accuracy systematic reviews were reanalyzed with the
Moses-Littenberg model, using equal weighting ("E-ML") and weighting by the
inverse variance of the log DOR ("W-ML"), and with the HSROC model. The
diagnostic odds ratios (DORs) were estimated and covariates added to both models
to estimate relative DORs (RDORs) between subgroups. Models were compared by
calculating the ratio of DORs, the ratio of RDORs, and P-values for detecting
asymmetry and effects of covariates on DOR. RESULTS: Compared to the HSROC model,
the Moses-Littenberg model DOR estimates were a median of 22% ("E-ML") and 47%
("W-ML") lower at Q*, and 7% and 42% lower at the central point in the data.
Instances of the ML models giving estimates higher than the HSROC model also
occurred. Investigations of heterogeneity also differed; the Moses-Littenberg
models on average estimating smaller differences in RDOR. CONCLUSIONS: Moses
Littenberg meta-analyses can generate lower estimates of test accuracy, and
smaller differences in accuracy, compared to mathematically superior hierarchical
models. This has implications for the usefulness of meta-analyses using this
approach. We recommend meta-analysis of diagnostic test accuracy studies to be
conducted using available hierarchical model-based approaches.
PMID- 27485294
TI - Hydantoin: The mechanism of its in vitro anti-enterovirus activity revisited.
AB - It has been generally accepted that hydantoin [5-(3,4
dichlorophenyl)methylhydantoin] exerts its anti-enterovirus activity by solely
inhibiting viral assembly. However, we here show that hydantoin inhibits
enteroviral RNA synthesis as well as subgenomic replication in a dose-dependent
manner. We demonstrate that inhibition of RNA synthesis is the predominant
mechanism of action at relatively high concentrations of hydantoin. However, at
lower concentrations inhibition of viral morphogenesis is the main mechanism of
action. Thus, hydantoin inhibits enteroviral replication by two distinct
mechanisms.
PMID- 27485295
TI - Tax on saturated fat-does it work?
PMID- 27485296
TI - Evolution of Nonmirror Image Fluorescence Spectra in Conjugated Polymers and
Oligomers.
AB - The nonmirror image relationship between absorption and fluorescence spectra of
conjugated polymers contrasts with most organic chromophores and is widely
considered a signature of interchromopohore energy funneling. We apply broad-band
ultrafast fluorescence spectroscopy to resolve the evolution of fluorescence
spectra for dilute solutions of conjugated oligothiophenes, where no energy
transfer is possible. Fluorescence spectra evolve from a mirror image of
absorption, which lacks vibronic structure, toward a spectrally narrower and
vibronically structured species on the hundreds of femtosecond to early
picosecond time scale. Our analysis of this fluorescence spectral evolution shows
that a broad distribution of torsional conformers is driven to rapidly planarize
in the excited state, including in solid films, which is supported by Raman
spectroscopy and quantum chemical modeling. Our data have important implications
for understanding different energy-transfer regimes that are delineated by
structural relaxation.
PMID- 27485298
TI - Spiritual Factors Predict State and Trait Anxiety.
AB - This research study was designed to examine the effect of spiritual well-being
and spirituality on state and trait anxiety. Two hundred and thirty-eight adults
in the USA were surveyed using the State-Trait Anxiety Inventory, Duke University
Religion Index, Spiritual Well-Being Scale, and Participant Questionnaire.
Results indicate that spiritual well-being can predict 39.1 % of an adult's state
anxiety and 37.9 % of trait anxiety. Furthermore, frequency of religious
attendance, frequency of private religious activity, and intrinsic religiosity
can predict 6.2 % of an adult's state anxiety and 8.6 % of trait anxiety.
Recommendations for researchers and implications for clinicians are discussed.
PMID- 27485299
TI - Neuroprotection induced by post-conditioning following ischemia/reperfusion in
mice is associated with altered microRNA expression.
AB - Ischemic preconditioning and ischemic postconditioning (IPostC) represent
promising strategies to reduce ischemia-reperfusion (I/R) injury and attenuate
the lethal ischemic damage following stroke. However, the mechanism underlying
this attenuation remains to be elucidated. It was hypothesized that alterations
in microRNA (miRNA) expression in the cerebral cortex and hippocampus of mice
following I/R is associated with the functional improvement induced by IPostC.
Behavioral changes were assessed in a mouse model of I/R in the absence or
presence of IPostC, followed by microarray analyses to investigate the
expressional alterations of miRNAs in the cerebral cortex and hippocampus of
mice. The results of the present study revealed that IPostC abrogated the
neurological impairment and hippocampus-associated cognitive deficits induced by
I/R, and upregulated or downregulated the expression levels of numerous miRNAs.
Furthermore, the upregulation of miR-19a, and the downregulation of miR-1, let-7f
and miR-124 expression levels following IPostC was confirmed utilizing reverse
transcription-quantitative polymerase chain reaction. The results of the present
study demonstrated that alterations in miRNA expression in the cerebral cortex
and hippocampus of mice following I/R was associated with the neuroprotection
induced by IPostC.
PMID- 27485300
TI - 'Quasi-Mixture' Descriptors for QSPR Analysis of Molecular Macroscopic
Properties. The Critical Properties of Organic Compounds.
AB - Rational approach towards the QSAR/QSPR modeling requires the descriptors to be
computationally efficient, yet physically and chemically meaningful. On the basis
of existing simplex representation of molecular structure (SiRMS) the novel
'quasi-mixture' descriptors were developed in order to accomplish the goal of
characterization molecules on 2D level (i.e. without explicit generation of 3D
structure and exhaustive conformational search) with account for potential
intermolecular interactions. The critical properties of organic compounds were
chosen as target properties for the estimation of descriptors' efficacy because
of their well-known physical nature, rigorously estimated experimental errors and
large quantity of experimental data. Among described properties are critical
temperature, pressure and volume. Obtained models have high statistical
characteristics, therefore showing the efficacy of suggested 'quasi-mixture'
approach. Moreover, 'quasi-mixture' approach, as a branch of the SiRMS, allows to
interpret results in terms of simple basic molecular properties. The obtained
picture of influences corresponds to the accepted theoretical views.
PMID- 27485301
TI - Global Performance and Trend of QSAR/QSPR Research: A Bibliometric Analysis.
AB - A bibliometric analysis based on the Science Citation Index Expanded was
conducted to provide insights into the publication performance and research trend
of quantitative structure-activity relationship (QSAR) and quantitative structure
property relationship (QSPR) from 1993 to 2012. The results show that the number
of articles per year quadrupled from 1993 to 2006 and plateaued since 2007.
Journal of Chemical Information and Modeling was the most prolific journal. The
internal methodological innovations in acquiring molecular descriptors and
modeling stimulated the articles' increase in the research fields of drug design
and synthesis, and chemoinformatics; while the external regulatory demands on
model validation and reliability fueled the increase in environmental sciences.
"Prediction endpoints", "statistical algorithms", and "molecular descriptors"
were identified as three research hotspots. The articles from developed countries
were larger in number and more influential in citation, whereas those from
developing countries were higher in output growth rates.
PMID- 27485297
TI - Impact of aerobic exercise on levels of IL-4 and IL-10: results from two
randomized intervention trials.
AB - The mechanisms whereby regular exercise reduces chronic inflammation remain
unclear. We investigated whether regular aerobic exercise alters basal levels of
interleukin (IL)-10 and IL-4 in two randomized trials of physical activity. The
Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA, n = 320) and
the Breast Cancer and Exercise Trial in Alberta (BETA, n = 400) were two-center,
two-armed randomized trials in inactive, healthy, postmenopausal women. Both
trials included an exercise intervention prescribed five times/week and no
dietary changes. In ALPHA, the exercise group was prescribed 225 min/week versus
no activity in the controls. BETA examined dose-response effects comparing 300
(HIGH) versus 150 (MODERATE) min/week. Plasma concentrations of IL-10 and IL-4
were measured at baseline, 6, and 12 months. Intention-to-treat (ITT) analysis
was performed using linear mixed models adjusted for baseline biomarker
concentrations. Circulating anti-inflammatory cytokine levels decreased among all
groups, with percent change ranging from -3.4% (controls) to -8.2% (HIGH) for IL
4 and -1.6% (controls) to -7.5% (HIGH) for IL-10. No significant group
differences were found for IL-4 (ALPHA P = 0.54; BETA P = 0.32) or IL-10 (ALPHA P
= 0.84; BETA P = 0.68). Some evidence for moderation of the effect of exercise by
baseline characteristics was found for IL-10 but not for IL-4. Results from these
two large randomized aerobic exercise intervention trials suggest that aerobic
exercise does not alter IL-10 or IL-4 in a manner consistent with chronic disease
and cancer prevention.
PMID- 27485302
TI - Computational Prediction of Drug?Target Interactions Using Chemical, Biological,
and Network Features.
AB - Drug?target interactions (DTIs) are central to current drug discovery processes.
Efforts have been devoted to the development of methodology for predicting DTIs
and drug?target interaction networks. Most existing methods mainly focus on the
application of information about drug or protein structure features. In the
present work, we proposed a computational method for DTI prediction by combining
the information from chemical, biological and network properties. The method was
developed based on a learning algorithm-random forest (RF) combined with
integrated features for predicting DTIs. Four classes of drug?target interaction
networks in humans involving enzymes, ion channels, G-protein-coupled receptors
(GPCRs) and nuclear receptors, are independently used for establishing predictive
models. The RF models gave prediction accuracy of 93.52 %, 94.84 %, 89.68 % and
84.72 % for four pharmaceutically useful datasets, respectively. The prediction
ability of our approach is comparative to or even better than that of other DTI
prediction methods. These comparative results demonstrated the relevance of the
network topology as source of information for predicting DTIs. Further analysis
confirmed that among our top ranked predictions of DTIs, several DTIs are
supported by databases, while the others represent novel potential DTIs. We
believe that our proposed approach can help to limit the search space of DTIs and
provide a new way towards repositioning old drugs and identifying targets.
PMID- 27485303
TI - Molecular Dynamics of Major Allergens from Alternaria, Birch Pollen and Peach.
AB - In the search for factors that make a protein allergenic (an issue that remains
so far elusive) some common features of allergens such as small size, high
stability and lipid binding are recognized in spite of their structural
diversity. Other relevant but still poorly understood feature is their capability
to form homodimers. We investigated by means of Molecular Dynamics (MD)
calculations the stability in solution of several dimers of three major allergens
from Alternaria mold, birch pollen, and peach fruit known to play essential roles
in allergic disease. By running 20 ns MD simulations we found essential
properties on solution that provide information of interest on their
dimerization, stability of their epitopes and dynamical features of ligand
binding cavities. Our results show that three essential allergen proteins display
a distinct behavior on their trends to form homodimers in solution.
PMID- 27485304
TI - Interaction of Flaviviruses with Reproduction Inhibitors Binding in beta-OG
Pocket: Insights from Molecular Dynamics Simulations.
AB - Flaviviral diseases, including dengue fever, West Nile fever, yellow fever, tick
borne encephalitis, Omsk haemorrhagic fever, and Powassan encephalitis, threaten
human health all over the world. Lack of effective antivirals targeting
replication cycle of flaviviruses makes the search of such compounds a
challenging task. Recently we have identified a reproduction inhibitor effective
against tick-borne encephalitis virus and Powassan virus (POWV) (ACS Med. Chem.
Lett., 2013, 4, 869-874). To enable using this inhibitor as a template for 3D
pharmacophore search, a biologically active conformation of this molecule should
have been established. Here we performed molecular dynamics simulations of the
complexes between the different enantiomers of the inhibitor and POWV envelope
(E) proteins, putative targets of the inhibitor, in the different protonation
states corresponding to the different stages of membrane fusion process. Several
stable conformations of the inhibitor were identified, opening routes for further
design of more advanced molecules.
PMID- 27485305
TI - Erratum: Fractal Dimensions of Macromolecular Structures.
PMID- 27485308
TI - Evidence that birds sleep in mid-flight.
AB - Many birds fly non-stop for days or longer, but do they sleep in flight and if
so, how? It is commonly assumed that flying birds maintain environmental
awareness and aerodynamic control by sleeping with only one eye closed and one
cerebral hemisphere at a time. However, sleep has never been demonstrated in
flying birds. Here, using electroencephalogram recordings of great frigatebirds
(Fregata minor) flying over the ocean for up to 10 days, we show that they can
sleep with either one hemisphere at a time or both hemispheres simultaneously.
Also unexpectedly, frigatebirds sleep for only 0.69 h d(-1) (7.4% of the time
spent sleeping on land), indicating that ecological demands for attention usually
exceed the attention afforded by sleeping unihemispherically. In addition to
establishing that birds can sleep in flight, our results challenge the view that
they sustain prolonged flights by obtaining normal amounts of sleep on the wing.
PMID- 27485306
TI - Altered corticospinal function during movement preparation in humans with spinal
cord injury.
AB - KEY POINTS: In uninjured humans, transmission in the corticospinal pathway
changes in a task-dependent manner during movement preparation. We investigated
whether this ability is preserved in humans with incomplete chronic cervical
spinal cord injury (SCI). Our results show that corticospinal excitability is
altered in the preparatory phase of an upcoming movement when there is a need to
suppress but not to execute rapid index finger voluntary contractions in
individuals with SCI compared with controls. This is probably related to impaired
transmission at a cortical and spinal level after SCI. Overall our findings
indicate that deficits in corticospinal transmission in humans with chronic
incomplete SCI are also present in the preparatory phase of upcoming movements.
ABSTRACT: Corticospinal output is modulated in a task-dependent manner during the
preparatory phase of upcoming movements in humans. Whether this ability is
preserved after spinal cord injury (SCI) is unknown. In this study, we examined
motor evoked potentials elicited by cortical (MEPs) and subcortical (CMEPs)
stimulation of corticospinal axons and short-interval intracortical inhibition in
the first dorsal interosseous muscle in the preparatory phase of a reaction time
task where individuals with chronic incomplete cervical SCI and age-matched
controls needed to suppress (NOGO) or initiate (GO) ballistic index finger
isometric voluntary contractions. Reaction times were prolonged in SCI
participants compared with control subjects and stimulation was provided ~90 ms
prior to movement onset in each group. During NOGO trials, both MEPs and CMEPs
remained unchanged compared to baseline in SCI participants but were suppressed
in control subjects. Notably, during GO trials, MEPs increased to a similar
extent in both groups but CMEPs increased only in controls. The magnitude of
short-interval intracortical inhibition increased in controls but not in SCI
subjects during NOGO trials and decreased in both groups in GO trials. These
novel observations reveal that humans with incomplete cervical SCI have an
altered ability to modulate corticospinal excitability during movement
preparation when there is a need to suppress but not to execute upcoming rapid
finger movements, which is probably related to impaired transmission at a
cortical and spinal level. Thus, deficits in corticospinal transmission after
human SCI extend to the preparatory phase of upcoming movements.
PMID- 27485307
TI - Mortality among head trauma patients taking preinjury antithrombotic agents: a
retrospective cohort analysis from a Level 1 trauma centre.
AB - BACKGROUND: Bleeding represents the most well-known and the most feared
complications caused by the use of antithrombotic agents. There is, however,
limited documentation whether pre-injury use of antithrombotic agents affects
outcome after head trauma. The aim of this study was to define the relationship
between the use of preinjury antithrombotic agents and mortality among elderly
people sustaining blunt head trauma. METHODS: A retrospective cohort analysis was
performed on the hospital based trauma registry at Oslo University Hospital.
Patients aged 55 years or older sustaining blunt head trauma between 2004 and
2006 were included. Multivariable logistic regression analyses were used to
identify independent predictors of 30-day mortality. Separate analyses were
performed for warfarin use and platelet inhibitor use. RESULTS: Of the 418
patients admitted with a diagnosis of head trauma, 137 (32.8 %) used pre-injury
antithrombotic agents (53 warfarin, 80 platelet inhibitors, and 4 both). Seventy
patients died (16.7 %); 15 (28.3 %) of the warfarin users, 12 (15.0 %) of the
platelet inhibitor users, and two (50 %) with combined use of warfarin and
platelet inhibitors, compared to 41 (14.6 %) of the non-users. There was a
significant interaction effect between warfarin use and the Triage Revised Trauma
Score collected upon the patients' arrival at the hospital. After adjusting for
potential confounders, warfarin use was associated with increased 30-day
mortality among patients with normal physiology (adjusted OR 8,3; 95 % CI, 2.0 to
34.8) on admission, but not among patients with physiological derangement on
admission. Use of platelet inhibitors was not associated with increased
mortality. CONCLUSIONS: The use of warfarin before trauma was associated with
increased 30-day mortality among a subset of patients. Use of platelet inhibitors
before trauma was not associated with increased mortality. These results indicate
that patients on preinjury warfarin may need closer monitoring and follow up
after trauma despite normal physiology on admission to the emergency department.
PMID- 27485309
TI - Abundant immunoglobulin (Ig)G4-positive plasma cells in interstitial pneumonia
without extrathoracic lesions of IgG4-related disease: is this finding specific
to IgG4-related lung disease?
AB - AIMS: There have been few reports on immunoglobulin-G4 (IgG4)-related
interstitial pneumonia (IP), and its clinical features remain unclear. The
objective of this study was to assess whether IP with marked IgG4-positive plasma
cell infiltration without extrathoracic lesions of IgG4-related disease (RD)
should be diagnosed as a subtype of IgG4-RD or a separate entity. METHODS AND
RESULTS: All consecutive patients with surgical lung biopsy-proven idiopathic IP
with an IgG4/IgG-positive cell ratio of >40% and >50 IgG4+ plasma cells in a high
power field without extrathoracic lesions of IgG4-RD were reviewed
retrospectively. Five patients were enrolled into this study. All patients were
male with a history of smoking. Four patients met the comprehensive diagnostic
criteria for IgG4-RD. The remaining patient lacked data related to the serum IgG4
level. Histologically, a non-specific IP pattern was observed in all patients.
The key morphological features of IgG4-RD, such as storiform fibrosis and
obliterative phlebitis with lymphoplasmacytic infiltration in a loose background
texture, were absent in every patient. In contrast, venule obstruction by densely
packed lymphoplasmacytic infiltration was observed in two patients. Marked
scarring and remodelling of the lung were also noted, which is not seen typically
in IgG4-RD. A favourable response to corticosteroid monotherapy was observed in
all patients; however, two patients developed lung cancer during the course of
observation. CONCLUSIONS: IP with marked IgG4-positive plasma cell infiltration
without extrathoracic lesions of IgG4-RD had different pathological features from
those of IgG4-RD, and it is appropriate to regard this as a separate entity.
PMID- 27485311
TI - Commentary to "Effect of postoperative weight gain on the risk of channel
revision following continent catheterizable urinary channel surgery".
PMID- 27485310
TI - Rbfox2 function in RNA metabolism is impaired in hypoplastic left heart syndrome
patient hearts.
AB - Hypoplastic left heart syndrome (HLHS) is a fatal congenital heart disease in
which the left side of the heart is underdeveloped, impairing the systemic
circulation. Underdeveloped left ventricle exerts biomechanical stress on the
right ventricle that can progress into heart failure. Genome-wide transcriptome
changes have been identified at early stages in the right ventricle (RV) of
infants with HLHS, although the molecular mechanisms remain unknown. Here, we
demonstrate that the RNA binding protein Rbfox2, which is mutated in HLHS
patients, is a contributor to transcriptome changes in HLHS patient RVs. Our
results indicate that majority of transcripts differentially expressed in HLHS
patient hearts have validated Rbfox2 binding sites. We show that Rbfox2 regulates
mRNA levels of targets with 3'UTR binding sites contributing to aberrant gene
expression in HLHS patients. Strikingly, the Rbfox2 nonsense mutation identified
in HLHS patients truncates the protein, impairs its subcellular distribution and
adversely affects its function in RNA metabolism. Overall, our findings uncover a
novel role for Rbfox2 in controlling transcriptome in HLHS.
PMID- 27485312
TI - Structural basis for misregulation of kinesin KIF21A autoinhibition by CFEOM1
disease mutations.
AB - Tight regulation of kinesin activity is crucial and malfunction is linked to
neurological diseases. Point mutations in the KIF21A gene cause congenital
fibrosis of the extraocular muscles type 1 (CFEOM1) by disrupting the
autoinhibitory interaction between the motor domain and a regulatory region in
the stalk. However, the molecular mechanism underlying the misregulation of
KIF21A activity in CFEOM1 is not understood. Here, we show that the KIF21A
regulatory domain containing all disease-associated substitutions in the stalk
forms an intramolecular antiparallel coiled coil that inhibits the kinesin.
CFEOM1 mutations lead to KIF21A hyperactivation by affecting either the
structural integrity of the antiparallel coiled coil or the autoinhibitory
binding interface, thereby reducing its affinity for the motor domain.
Interaction of the KIF21A regulatory domain with the KIF21B motor domain and
sequence similarities to KIF7 and KIF27 strongly suggest a conservation of this
regulatory mechanism in other kinesin-4 family members.
PMID- 27485313
TI - Label-free optical quantification of structural alterations in Alzheimer's
disease.
AB - We present a wide-field quantitative label-free imaging of mouse brain tissue
slices with sub-micrometre resolution, employing holographic microscopy and an
automated scanning platform. From the measured light field images, scattering
coefficients and anisotropies are quantitatively retrieved by using the modified
the scattering-phase theorem, which enables access to structural information
about brain tissues. As a proof of principle, we demonstrate that these
scattering parameters enable us to quantitatively address structural alteration
in the brain tissues of mice with Alzheimer's disease.
PMID- 27485314
TI - A Biodegradable Polydopamine-Derived Electrode Material for High-Capacity and
Long-Life Lithium-Ion and Sodium-Ion Batteries.
AB - Polydopamine (PDA), which is biodegradable and is derived from naturally
occurring products, can be employed as an electrode material, wherein
controllable partial oxidization plays a key role in balancing the proportion of
redox-active carbonyl groups and the structural stability and conductivity.
Unexpectedly, the optimized PDA derivative endows lithium-ion batteries (LIBs) or
sodium-ion batteries (SIBs) with superior electrochemical performances, including
high capacities (1818 mAh g(-1) for LIBs and 500 mAh g(-1) for SIBs) and good
stable cyclabilities (93 % capacity retention after 580 cycles for LIBs; 100 %
capacity retention after 1024 cycles for SIBs), which are much better than those
of their counterparts with conventional binders.
PMID- 27485315
TI - Social Network Behavior and Engagement Within a Smoking Cessation Facebook Page.
AB - BACKGROUND: Social media platforms are increasingly being used to support
individuals in behavior change attempts, including smoking cessation. Examining
the interactions of participants in health-related social media groups can help
inform our understanding of how these groups can best be leveraged to facilitate
behavior change. OBJECTIVE: The aim of this study was to analyze patterns of
participation, self-reported smoking cessation length, and interactions within
the National Cancer Institutes' Facebook community for smoking cessation support.
METHODS: Our sample consisted of approximately 4243 individuals who interacted
(eg, posted, commented) on the public Smokefree Women Facebook page during the
time of data collection. In Phase 1, social network visualizations and centrality
measures were used to evaluate network structure and engagement. In Phase 2, an
inductive, thematic qualitative content analysis was conducted with a subsample
of 500 individuals, and correlational analysis was used to determine how
participant engagement was associated with self-reported session length. RESULTS:
Between February 2013 and March 2014, there were 875 posts and 4088 comments from
approximately 4243 participants. Social network visualizations revealed the
moderator's role in keeping the community together and distributing the most
active participants. Correlation analyses suggest that engagement in the network
was significantly inversely associated with cessation status (Spearman
correlation coefficient = -0.14, P=.03, N=243). The content analysis of 1698
posts from 500 randomly selected participants identified the most frequent
interactions in the community as providing support (43%, n=721) and announcing
number of days smoke free (41%, n=689). CONCLUSIONS: These findings highlight the
importance of the moderator for network engagement and provide helpful insights
into the patterns and types of interactions participants are engaging in. This
study adds knowledge of how the social network of a smoking cessation community
behaves within the confines of a Facebook group.
PMID- 27485316
TI - Relational categories are more mutable than entity categories.
AB - Across three experiments, we explore differences between relational categories
whose members share common relational patterns-and entity categories, whose
members share common intrinsic properties. Specifically, we test the claim that
relational concepts are more semantically mutable in context, and therefore less
stable in memory, than entity concepts. We compared memory for entity nouns and
relational nouns, tested either in the same context as at encoding or in a
different context. We found that (a) participants show better recognition
accuracy for entity nouns than for relational nouns, and (b) recognition of
relational nouns is more impaired by a change in context than is recognition of
entity nouns. We replicated these findings even when controlling for factors
highly correlated with relationality, such as abstractness-concreteness. This
suggests that the contextual mutability of relational concepts is due to the core
semantic property of conveying relational structure and not simply to
accompanying characteristics such as abstractness. We note parallels with the
distinction between nouns and verbs and suggest implications for lexical and
conceptual structure. Finally, we relate these patterns to proposals that a deep
distinction exists between words with an essentially referential function and
those with a predicate function.
PMID- 27485317
TI - Estimation of genetic parameters and detection of chromosomal regions affecting
the major milk proteins and their post translational modifications in Danish
Holstein and Danish Jersey cattle.
AB - BACKGROUND: In the Western world bovine milk products are an important protein
source in human diet. The major proteins in bovine milk are the four caseins
(CN), alphaS1-, alphaS2-, beta-, and k-CN and the two whey proteins, beta-LG and
alpha-LA. It has been shown that both the amount of specific CN and their
isoforms including post-translational modifications (PTM) influence technological
properties of milk. Therefore, the aim of this study was to 1) estimate genetic
parameters for individual proteins in Danish Holstein (DH) (n = 371) and Danish
Jersey (DJ) (n = 321) milk, and 2) detect genomic regions associated with
specific milk protein and their different PTM forms using a genome-wide
association study (GWAS) approach. RESULTS: For DH, high heritability estimates
were found for protein percentage (0.47), casein percentage (0.43), k-CN (0.77),
beta-LG (0.58), and alpha-LA (0.40). For DJ, high heritability estimates were
found for protein percentage (0.70), casein percentage (0.52), and alpha-LA
(0.44). The heritability for G-k-CN, U-k-CN and GD was higher in the DH compared
to the DJ, whereas the heritability for the PD of alphaS1-CN was lower in DH
compared to DJ, whereas the PD for alphaS2-CN was higher in DH compared to DJ.
The GWAS results for the main milk proteins were in line what has been earlier
published. However, we showed that there were SNPs specifically regulating G-k-CN
in DH. Some of these SNPs were assigned to casein protein kinase genes (CSNK1G3,
PRKCQ). CONCLUSION: The genetic analysis of the major milk proteins and their PTM
forms revealed that these were heritable in both DH and DJ. In DH, genomic
regions specific for glycosylation of k-CN were detected. Furthermore, genomic
regions for the major milk proteins confirmed the regions on BTA6 (casein
cluster), BTA11 (PEAP), and BTA14 (DGAT1) as important regions influencing
protein composition in milk. The results from this study provide confidence that
it is possible to breed for specific milk protein including the different PTM
forms.
PMID- 27485318
TI - Influence of asthma status on sleep variability in overweight/obese youth.
AB - OBJECTIVE: Pediatric asthma and overweight/obesity (OV/OB) frequently co-occur
and youth with both conditions exhibit poor sleep/bedtime habits. This study
assessed differences in week-to-weekend bedtime/wake time variability among OV/OB
youth with/without comorbid asthma, and tested whether variability predicted
weekday sleep. METHODS: OV/OB youth (n = 142; 28% comorbid asthma; 7-12 years)
wore an Accelerometer for 5 days (2 weekend days), providing estimates of week-to
weekend bedtime/wake-time variability, weekday Total Sleep Time (TST), weekday
time in bed (TIB), and weekday wake after sleep onset (WASO). RESULTS: There were
no demographic differences between groups beyond lower family income for the
OV/OB+asthma group. The OV/OB+asthma group exhibited later weekday (mean
OV/OB+asthma = 10:39 pm, mean OV/OB only = 10:30pm) and weekend (mean
OV/OB+asthma = 11:41 pm, mean OV/OB only = 11:17pm) bedtimes, earlier weekday
waketimes (mean OV/OB+asthma = 6:40 am, mean OV/OB only = 6:51 am), and similar
weekend waketimes (mean OV/OB+asthma = 7:54 pm, mean OV/OB only = 7:52 pm.
Univariate MANOVA follow-ups indicated a main effect of asthma group for week-to
weekend bedtime and waketime variability, with the OV/OB+asthma group evidencing
approximately 30 minutes greater bedtime (OV/OB+asthma mean = 90 minutes) and
waketime (OV/OB+asthma mean = 108 minutes) variability. Within the OV/OB+asthma
group, greater waketime variability predicted fewer minutes of weekday TIB and
WASO. Within the OV/OB only group, wake time variability predicted fewer minutes
of weekday TIB. CONCLUSION: Findings suggest that asthma status confers risk for
more week-to-weekend variability among currently OV/OB youth, and that greater
variability shortens the weekday sleep period. Further research on reasons for
greater week-to-weekend sleep variability in asthma is needed.
PMID- 27485319
TI - Prevalence of glutamine deficiency in ICU patients: a cross-sectional analytical
study.
AB - BACKGROUND: Not only is glutamine deficiency an independent predictor of
mortality in intensive care unit (ICU) patients, but glutamine supplementation is
also recommended for its proven outcome benefits. However, recent data suggest
that early glutamine supplementation in certain patient groups increase
mortality. The aim of this study was to investigate plasma glutamine levels of
adult ICU patients in the South African setting and to determine relationships
between glutamine levels, gender, diagnostic categories and selected inflammatory
markers. The data from this study will be used as baseline measurement to support
a large scale study that will be undertaken in the South African ICU population.
METHODS: This cross-sectional, analytical study included 60 mixed adult ICU
patients within 24 h post ICU admission. Plasma glutamine levels were determined
on admission. The relationship between glutamine levels, Interleukin-6 (IL-6) and
C-reactive protein (CRP); as well as gender- and diagnosis-related differences in
glutamine levels were also investigated. A non-parametric ROC curve was computed
to determine the CRP concentration cut-off point above which glutamine becomes
deficient. RESULTS: The median plasma glutamine level (497 MUmol/L) was in the
normal range; however, 38.3 % (n = 23) of patients had deficient (<420 MUmol/L)
and 6.7 % (n = 4) had supra-normal glutamine levels (>930 MUmol/L). No
significant difference could be detected between glutamine levels and gender or
diagnosis categories as a group. When only the medical and surgical categories
were compared, the median plasma glutamine level of the medical patients were
significantly lower than that of the surgical patients (p = 0.042). Glutamine
showed inverse associations with CRP levels (r = -0.44, p < 0.05) and IL-6
concentrations (r = -0.23, p = 0.08). A CRP cut-off value of 95.5 mg/L was
determined above which glutamine levels became deficient. CONCLUSIONS: About a
third of patients (38 %) were glutamine deficient on admission to ICU, whereas
some presented with supra-normal levels. While glutamine levels correlated
inversely with inflammatory markers, and a CRP value of above 95.5 mg/L indicated
potential glutamine deficiency, the clinical application of this finding needs
further investigation.
PMID- 27485320
TI - Immunomodulatory effects of Longdan Xiegan Tang on CD4+/CD8+ T cells and
associated inflammatory cytokines in rats with experimental autoimmune uveitis.
AB - Longdan Xiegan Tang (LXT) is a mixture of herbal extracts commonly used in
traditional Chinese medicine that may exert immunomodulatory effects for the
treatment of autoimmune diseases. However, the detailed mechanisms that mediate
the actions of LXT are unclear. The present study induced an experimental
autoimmune uveitis (EAU) model in Lewis rats via injection of IRBP1177-1191
emulsion. The model was used to investigate the effects of LXT on EAU rats and
assess the efficacy of LXT by measuring clinical manifestations and
histopathological changes caused by EAU. Additionally, alterations in the ratio
of CD4+/CD8+-T cells were determined by flow cytometry, and the expression of
interferon (IFN)-gamma, interleukin (IL)-17, IL-10 and tumor necrosis factor
(TNF)-alpha were measured using reverse transcription-quantitative polymerase
chain reaction and enzyme-linked immunosorbent assay analysis. The results of the
present study demonstrate that LXT can efficiently alleviate the symptoms of EAU,
inhibit the differentiation of uveitogenic CD4+ T cells and reduce the expression
of proinflammatory cytokines, including IFN-gamma, IL-17 and TNF-alpha.
Furthermore, LXT promotes the production of IL-10 and accelerates the recovery of
EAU, indicating that the immunomodulatory effects of LXT may potentially be used
for the treatment of uveitis.
PMID- 27485321
TI - Synaptic plasticity and spatial working memory are impaired in the CD mouse model
of Williams-Beuren syndrome.
AB - Mice heterozygous for a complete deletion (CD) equivalent to the most common
deletion found in individuals with Williams-Beuren syndrome (WBS) recapitulate
relevant features of the neurocognitive phenotype, such as hypersociability,
along with some neuroanatomical alterations in specific brain areas. However, the
pathophysiological mechanisms underlying these phenotypes still remain largely
unknown. We have studied the synaptic function and cognition in CD mice using
hippocampal slices and a behavioral test sensitive to hippocampal function. We
have found that long-term potentiation (LTP) elicited by theta burst stimulation
(TBS) was significantly impaired in hippocampal field CA1 of CD animals. This
deficit might be associated with the observed alterations in spatial working
memory. However, we did not detect changes in presynaptic function, LTP induction
mechanisms or AMPA and NMDA receptor function. Reduced levels of Brain-derived
neurotrophic factor (BDNF) were present in the CA1-CA3 hippocampal region of CD
mice, which could account for LTP deficits in these mice. Taken together, these
results suggest a defect of CA1 synapses in CD mice to sustain synaptic strength
after stimulation. These data represent the first description of synaptic
functional deficits in CD mice and further highlights the utility of the CD model
to study the mechanisms underlying the WBS neurocognitive profile.
PMID- 27485322
TI - Precarious employment is a risk factor for poor mental health in young
individuals in Sweden: a cohort study with multiple follow-ups.
AB - BACKGROUND: The globalisation of the economy and the labour markets has resulted
in a growing proportion of individuals who find themselves in a precarious labour
market situation, especially among the young. This pertains also to the Nordic
countries, despite their characterisation as well developed welfare states with
active labour market policies. This should be viewed against the background of a
number of studies, which have shown that several aspects of precarious employment
are detrimental to mental health. However, longitudinal studies from the Nordic
region that examine the impact of precarious labour market conditions on mental
health in young individuals are currently lacking. The present study aims to
examine this impact in a general cohort of Swedish young people. METHODS: Postal
questionnaires were sent out in 1999/2000 to a stratified random sample of the
Scania population, Sweden; the response rate was 58 %. All of those who responded
at baseline were invited to follow-ups after 5 and 10 years. Employment
precariousness was determined based on detailed questions about present
employment, previous unemployment, and self-rated risk of future unemployment.
Mental health was assessed by GHQ-12. For this study individuals in the age range
of 18-34 years at baseline, who were active in the labour market (employed or
seeking job) and had submitted complete data from 1999/2000, 2005, and 2010 on
employment precariousness and mental health status, were selected (N = 1135).
RESULTS: Forty-two percent of the participants had a precarious employment
situation at baseline. Labour market trajectories that included precarious
employment in 1999/2000 or 2005 predicted poor mental health in 2010: the
incidence ratio ratio was 1.4 (95 % CI: 1.1-2.0) when excluding all individuals
with mental health problems at baseline and adjusting for age, gender, social
support, social capital, and economic difficulties in childhood. The population
attributable fraction regarding poor mental health in the studied age group was
18 %. CONCLUSIONS: This study supported the hypothesis that precarious employment
should be regarded as an important social determinant for subsequent development
of mental health problems in previously mentally healthy young people.
PMID- 27485323
TI - MRI-detected osteitis is not associated with the presence or level of ACPA alone,
but with the combined presence of ACPA and RF.
AB - BACKGROUND: In rheumatoid arthritis (RA) bone marrow edema (BME, osteitis) and
anti-citrullinated protein antibodies (ACPA) are associated with radiographic
progression. ACPA have been associated with BME, but it is unknown if this
association is confined to ACPA and BME. We performed cross-sectional analysis of
the association of ACPA, rheumatoid factor (RF) and anti-carbamylated protein
(anti-CarP) antibodies with BME and other types of inflammation (synovitis,
tenosynovitis) detected by magnetic resonance imaging (MRI). METHODS: Disease
modifying antirheumatic drug (DMARD)-naive patients with early arthritis (n =
589), included in the Leiden Early Arthritis Clinic cohort, underwent contrast
enhanced 1.5 T MRI of unilateral wrist, metacarpophalangeal and
metatarsophalangeal-joints at baseline. BME, synovitis and tenosynovitis were
scored by two readers. ACPA, rheumatoid factor (RF) and anti-CarP were determined
at baseline. RESULTS: In univariable analyses ACPA-positive patients had higher
BME scores than ACPA-negative patients (median 4.5 vs. 2.0, p < 0.001), but not
more synovitis and tenosynovitis. Also RF (median 3.75 vs. 2.0, p < 0.001) and
anti-CarP antibodies (median 3.5 vs. 2.5, p = 0.012) were associated with higher
BME scores. Because the autoantibodies were concomitantly present, analyses were
stratified for the presence of different autoantibody combinations. ACPA-positive
(ACPA+), RF-negative (RF-), anti-CarP-negative (anti-CarP-) patients did not have
higher BME-scores than ACPA-negative (ACPA-), RF-, anti-CarP- patients. However
ACPA+, RF-positive (RF+), anti-CarP- patients and ACPA+, RF+, anti-CarP-positive
(anti-CarP+) patients had higher BME scores than ACPA-, RF-, anti-CarP- patients
(median 5.0 and 4.5 vs. 2.0, p < 0.001 and p < 0.001). ACPA levels were not
associated with BME scores. Analyses within RA- and UA-patients revealed similar
results. CONCLUSIONS: The presence of ACPA alone or ACPA level was not
statistically significantly associated with BME scores, but the combined presence
of ACPA and RF was associated with more BME. This suggests an additive role of RF
to ACPA in mediating osteitis.
PMID- 27485324
TI - Utility of repeat cytological assessment of thyroid nodules initially classified
as benign: clinical insights from multidisciplinary care in an Irish tertiary
referral centre.
AB - BACKGROUND: Fine needle aspiration biopsy (FNAB) is the tool of choice for
evaluating thyroid nodules with the majority classified as benign following
initial assessment. However, concern remains about false negative results and
some guidelines have recommended routine repeat aspirates. We aimed to assess the
utility of routine repeat FNAB for nodules classified as benign on initial biopsy
and to examine the impact of establishing a multidisciplinary team for the care
of these patients. METHODS: We performed a retrospective review of 400
consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our
hospital between July 2008 and July 2011. Data recorded included demographic,
clinical, histological and radiological variables. RESULTS: Three hundred and
fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two
hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of
routine repeat biopsy increased significantly over the time course of the study
(p for trend = 0.012). Nine Thy 2 nodules were classified differently on the
basis of routine repeat biopsy; one patient was classified as malignant on repeat
biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified
as a follicular lesions on repeat biopsy-six diagnosed as benign following
lobectomy; two declined lobectomy and were followed radiologically with no nodule
size increase. CONCLUSIONS: The false negative rate of an initial benign cytology
result, from a thyroid nodule aspirate, is low. In the setting of an experienced
multidisciplinary thyroid team, routine repeat aspiration is not justified.
PMID- 27485325
TI - Diagnostic Efficiency of Caregiver Report on the SCARED for Identifying Youth
Anxiety Disorders in Outpatient Settings.
AB - This study investigated the diagnostic and clinical utility of the parent-rated
Screen for Child Anxiety Related Emotional Disorders (SCARED-P) for detecting
youth anxiety disorders. Youth ages 6 to 12 years, 11 months were recruited from
9 outpatient mental health clinics (N = 707). Consensus diagnoses were based on
semistructured interviews (Schedule for Affective Disorders and Schizophrenia for
School-Age Children) with youth and caregivers; 31% were diagnosed with at least
one anxiety disorder. Caregivers completed the SCARED-P to describe youth anxiety
levels. SCARED-P scores were not considered during the consensus diagnoses. Areas
under the curve (AUCs) from receiver operating characteristic analyses and
diagnostic likelihood ratios (DLRs) quantified performance of the SCARED-P total
score and subscale scores (generalized anxiety disorder and separation anxiety
disorder). SCARED-P total scores had variable efficiency (AUCs = .69-.88), and
Generalized Anxiety Disorder and Separation Anxiety subscale scores were
excellent (AUCs = .86-.89) for identifying specific anxiety disorders. Optimal
subscale cutoff scores were computed to help rule in (DLRs = 2.7-5.4) or rule out
(DLRs < 1.0) anxiety disorders among youth. Results suggest that the Generalized
Anxiety Disorder and Separation Anxiety SCARED-P subscales accurately identify
their respective matched diagnoses. DLRs may aid clinicians in screening for
youth anxiety disorders and improve accuracy of diagnosis.
PMID- 27485326
TI - Cell-Free Production of Membrane Proteins in Escherichia coli Lysates for
Functional and Structural Studies.
AB - The complexity of membrane protein synthesis is largely reduced in cell-free
systems and it results into high success rates of target expression. Protocols
for the preparation of bacterial lysates have been optimized in order to ensure
reliable efficiencies in membrane protein production that are even sufficient for
structural applications. The open accessibility of the semisynthetic cell-free
expression reactions allows to adjust membrane protein solubilization conditions
according to the optimal folding requirements of individual targets. Two basic
strategies will be exemplified. The post-translational solubilization of membrane
proteins in detergent micelles is most straightforward for crystallization
approaches. The co-translational integration of membrane proteins into preformed
nanodiscs will enable their functional characterization in a variety of natural
lipid environments.
PMID- 27485327
TI - Membrane Protein Production in the Yeast, S. cerevisiae.
AB - The first crystal structures of recombinant mammalian membrane proteins were
solved in 2005 using protein that had been produced in yeast cells. One of these,
the rabbit Ca(2+)-ATPase SERCA1a, was synthesized in Saccharomyces cerevisiae.
All host systems have their specific advantages and disadvantages, but yeast has
remained a consistently popular choice in the eukaryotic membrane protein field
because it is quick, easy and cheap to culture, whilst being able to post
translationally process eukaryotic membrane proteins. Very recent structures of
recombinant membrane proteins produced in S. cerevisiae include those of the
Arabidopsis thaliana NRT1.1 nitrate transporter and the fungal plant pathogen
lipid scramblase, TMEM16. This chapter provides an overview of the methodological
approaches underpinning these successes.
PMID- 27485328
TI - Membrane Protein Production in Escherichia coli: Protocols and Rules.
AB - Functional and structural studies on membrane proteins are limited by the
difficulty to produce them in large amount and in a functional state. In this
review, we provide protocols to achieve high-level expression of membrane
proteins in Escherichia coli. The T7 RNA polymerase-based expression system is
presented in detail and protocols to assess and improve its efficiency are
discussed. Protocols to isolate either membrane or inclusion bodies and to
perform an initial qualitative test to assess the solubility of the recombinant
protein are also included.
PMID- 27485329
TI - Codon Optimizing for Increased Membrane Protein Production: A Minimalist
Approach.
AB - Reengineering a gene with synonymous codons is a popular approach for increasing
production levels of recombinant proteins. Here we present a minimalist
alternative to this method, which samples synonymous codons only at the second
and third positions rather than the entire coding sequence. As demonstrated with
two membrane-embedded transporters in Escherichia coli, the method was more
effective than optimizing the entire coding sequence. The method we present is
PCR based and requires three simple steps: (1) the design of two PCR primers, one
of which is degenerate; (2) the amplification of a mini-library by PCR; and (3)
screening for high-expressing clones.
PMID- 27485330
TI - Generation of Tetracycline-Inducible Mammalian Cell Lines by Flow Cytometry for
Improved Overproduction of Membrane Proteins.
AB - Overexpression of mammalian membrane proteins in mammalian cells is an effective
strategy to produce sufficient protein for biophysical analyses and structural
studies, because the cells generally express proteins in a correctly folded
state. However, obtaining high levels of expression suitable for protein
purification on a milligram scale can be challenging. As membrane protein
overexpression often has a negative impact on cell viability, it is usual to make
stable cell lines where the protein of interest is expressed from an inducible
promoter. Here we describe a methodology for optimizing the inducible production
of any membrane protein fused to GFP through the isolation of clonal cell lines.
Flow cytometry is used to sort uninduced cells and the most fluorescent 5 % of
the cell population are used to make clonal cell lines.
PMID- 27485331
TI - Membrane Protein Production in Lactococcus lactis for Functional Studies.
AB - Due to their unique properties, expression and study of membrane proteins in
heterologous systems remains difficult. Among the bacterial systems available,
the Gram-positive lactic bacterium, Lactococcus lactis, traditionally used in
food fermentations, is nowadays widely used for large-scale production and
functional characterization of bacterial and eukaryotic membrane proteins. The
aim of this chapter is to describe the different possibilities for the functional
characterization of peripheral or intrinsic membrane proteins expressed in
Lactococcus lactis.
PMID- 27485332
TI - Expression of Viral Envelope Glycoproteins in Drosophila melanogaster S2 Cells.
AB - The expression of recombinant viral envelope glycoproteins in S2 (Drosophila
melanogaster) has been performed with good results. This chapter contains
protocols for the utilization of this system for the expression and analysis of
proteins presented in cell plasma membrane.
PMID- 27485333
TI - Leishmania tarentolae as a Promising Tool for Expressing Polytopic and Multi
Transmembrane Spans Eukaryotic Membrane Proteins: The Case of the ABC Pump ABCG6.
AB - This chapter includes a practical method of membrane protein production in
Leishmania tarentolae cells. We routinely use it to express membrane proteins of
the ABC (adenosine triphosphate-binding cassette) family, here exemplified with
ABCG6 from L. braziliensis, implicated in phospholipid trafficking and drug
efflux. The pLEXSY system used here allows membrane protein production with a
mammalian-like N-glycosylation pattern, at high levels and at low costs. Also the
effects of an N-terminal truncation of the protein are described. The method is
described to allow any kind of membrane protein production.
PMID- 27485334
TI - Overexpression, Membrane Preparation, and Purification of a Typical Multidrug ABC
Transporter BmrA.
AB - The production and purification is normally the first step in any biophysical or
biochemical study of a new target protein. For membrane proteins, due to their
generally low expression levels and hydrophobic properties this is often a major
hurdle. Some multidrug transporters are members of one of the largest families of
membrane proteins, the ABC ("ATP-binding cassette"), and are responsible for the
uptake and export of a wide variety of molecules. This can lead to resistance
when those molecules are antibiotics or chemotherapy drugs. To better understand
their role in multidrug resistance pure and active protein is required. Here we
outline a protocol to produce a highly pure and functionally active multidrug
transporter BmrA that is suitable for use in biophysical and biochemical studies.
We show that BmrA can be heterologously overexpressed in huge amount in E. coli
and extracted from the membrane in a functionally active form.
PMID- 27485335
TI - Expression of Eukaryotic Membrane Proteins in Pichia pastoris.
AB - A key point when it comes to heterologous expression of eukaryotic membrane
proteins (EMPs) is the choice of the best-suited expression platform. The yeast
Pichia pastoris has proven to be a very versatile system showing promising
results in a growing number of cases. Indeed, its particular methylotrophic
characteristics combined to the very simple handling of a eukaryotic
microorganism that possesses the majority of mammalian-like machineries make it a
very competitive expression system for various complex proteins, in amounts
compatible with functional and structural studies. This chapter describes a set
of robust methodologies routinely used for the successful expression of a variety
of EMPs, going from yeast transformation with the recombinant plasmid to the
analysis of the quality and quantity of the proteins produced.
PMID- 27485336
TI - Integral Membrane Protein Expression in Saccharomyces cerevisiae.
AB - Eukaryotic integral membrane proteins are challenging targets for crystallography
or functional characterization in a purified state. Since expression is often a
limiting factor when studying this difficult class of biological macromolecules,
the intent of this chapter is to focus on the expression of eukaryotic integral
membrane proteins (IMPs) using the model organism Saccharomyces cerevisiae. S.
cerevisiae is a prime candidate for the expression of eukaryotic IMPs because it
offers the convenience of using episomal expression plasmids, selection of
positive transformants, posttranslational modifications, and it can properly fold
and target IMPs. Here we present a generalized protocol and insights based on our
collective knowledge as an aid to overcoming the challenges faced when expressing
eukaryotic IMPs in S. cerevisiae.
PMID- 27485337
TI - High-Throughput Baculovirus Expression System for Membrane Protein Production.
AB - The ease of use, robustness, cost-effectiveness, and posttranslational machinery
make baculovirus expression system a popular choice for production of eukaryotic
membrane proteins. This system can be readily adapted for high-throughput
operations. This chapter outlines the techniques and procedures for cloning,
transfection, small-scale production, and purification of membrane protein
samples in a high-throughput manner.
PMID- 27485338
TI - Small-Scale Screening to Large-Scale Over-Expression of Human Membrane Proteins
for Structural Studies.
AB - Membrane protein structural studies are frequently hampered by poor expression.
The low natural abundance of these proteins implies a need for utilizing
different heterologous expression systems. E. coli and yeast are commonly used
expression systems due to rapid cell growth at high cell density, economical
production, and ease of manipulation. Here we report a simplified, systematically
developed robust strategy from small-scale screening to large-scale over
expression of human integral membrane proteins in the mammalian expression system
for structural studies. This methodology streamlines small-scale screening of
several different constructs utilizing fluorescence size-exclusion chromatography
(FSEC) towards optimization of buffer, additives, and detergents for achieving
stability and homogeneity. This is followed by the generation of stable clonal
cell lines expressing desired constructs, and lastly large-scale expression for
crystallization. These techniques are designed to rapidly advance the structural
studies of eukaryotic integral membrane proteins including that of human membrane
proteins.
PMID- 27485339
TI - Purification of Human and Mammalian Membrane Proteins Expressed in Xenopus laevis
Frog Oocytes for Structural Studies.
AB - This protocol describes the isolation of recombinant human and mammalian membrane
proteins expressed in Xenopus laevis frog oocytes for structural studies. The
cDNA-derived cRNA of the desired genes is injected into several hundreds of
oocytes, which are incubated for several days to allow protein expression.
Recombinant proteins are then purified via affinity chromatography. The novelty
of this method comes from the design of a plasmid that produces multi-tagged
proteins and, most importantly, the development of a protocol for efficiently
discarding lipids, phospholipids, and lipoproteins from the oocyte egg yolk,
which represent the major contaminants in protein purifications. Thus, the high
protein purity and good yield obtained from this method allows protein structure
determination by transmission electron microscopy of single detergent-solubilized
protein particles and of 2D crystals of membrane protein embedded in lipid
bilayers. Additionally, a radiotracer assay for functional analysis of the
expressed target proteins in oocytes is described. Overall, this method is a
valuable option for structural studies of mammalian and particularly human
proteins, for which other expression systems often fail.
PMID- 27485340
TI - Membrane Protein Solubilization and Composition of Protein Detergent Complexes.
AB - Membrane proteins are typically expressed in heterologous systems with a view to
in vitro characterization. A critical step in the preparation of membrane
proteins after expression in any system is the solubilization of the protein in
aqueous solution, typically using detergents and lipids, to obtain the protein in
a form suitable for purification, structural or functional analysis. This process
is particularly difficult as the objective is to prepare the protein in an
unnatural environment, a protein detergent complex, separating it from its
natural lipid partners while causing the minimum destabilization or modification
of the structure. Although the process is difficult, and relatively hard to
master, an increasing number of membrane proteins have been successfully isolated
after expression in a wide variety of systems. In this chapter we give a general
protocol for preparing protein detergent complexes that is aimed at guiding the
reader through the different critical steps. In the second part of the chapter we
illustrate how to analyze the composition of protein detergent complexes; this
analysis is important as it has been found that compositional variation often
causes irreproducible results.
PMID- 27485341
TI - Detergent-Free Membrane Protein Purification.
AB - Membrane proteins are localized within a lipid bilayer; in order to purify them
for functional and structural studies the first step must involve solubilizing or
extracting the protein from these lipids. To date this has been achieved using
detergents which disrupt the bilayer and bind to the protein in the transmembrane
region. However finding conditions for optimal extraction, without destabilizing
protein structure, is time consuming and expensive. Here we present a recently
developed method using a styrene-maleic acid (SMA) co-polymer instead of
detergents. The SMA co-polymer extracts membrane proteins in a small disc of
lipid bilayer which can be used for affinity chromatography purification, thus
enabling the purification of membrane proteins while maintaining their native
lipid bilayer environment.
PMID- 27485342
TI - Conformational Dynamics and Interactions of Membrane Proteins by
Hydrogen/Deuterium Mass Spectrometry.
AB - Hydrogen/deuterium exchange associated with mass spectrometry has been recently
used to characterize the dynamics and the interactions of membrane proteins. Here
we describe experimental workflow enabling localization of the regions involved
in conformational changes or interactions.
PMID- 27485343
TI - Lessons from an alpha-Helical Membrane Enzyme: Expression, Purification, and
Detergent Optimization for Biophysical and Structural Characterization.
AB - This chapter outlines the protocol developed in our lab to produce a multipass
alpha-helical membrane protein. We present our work flow, from ortholog selection
to protein purification, including molecular biology for plasmid construction,
protein expression in E. coli, membrane isolation and detergent solubilization,
protein purification and tag removal, biophysical assessment of protein stability
in different detergents, and detergent concentration determination using thin
layer chromatography. We focus on results from our ongoing work with
intramembrane aspartyl proteases from archaeal organisms.
PMID- 27485344
TI - Method to Screen Multidrug Transport Inhibitors Using Yeast Overexpressing a
Human MDR Transporter.
AB - Multidrug resistance has appeared to mitigate the efficiency of anticancer drugs
and the possibility of successful cancer chemotherapy. The Hedgehog receptor
Patched is a multidrug transporter expressed in several cancers and as such it
represents a new target to circumvent chemotherapy resistance. In this chapter,
we describe the screening test developed to identify molecules able to inhibit
the drug efflux activity of Patched. This screening test uses yeast
overexpressing functional human Patched that have been shown to resist to
chemotherapeutic agents. This test can be adapted to other MDR transporters.
PMID- 27485345
TI - INC-Seq: accurate single molecule reads using nanopore sequencing.
AB - BACKGROUND: Nanopore sequencing provides a rapid, cheap and portable real-time
sequencing platform with the potential to revolutionize genomics. However,
several applications are limited by relatively high single-read error rates (>10
%), including RNA-seq, haplotype sequencing and 16S sequencing. RESULTS: We
developed the Intramolecular-ligated Nanopore Consensus Sequencing (INC-Seq) as a
strategy for obtaining long and accurate nanopore reads, starting with low input
DNA. Applying INC-Seq for 16S rRNA-based bacterial profiling generated full
length amplicon sequences with a median accuracy >97 %. CONCLUSIONS: INC-Seq
reads enabled accurate species-level classification, identification of species at
0.1 % abundance and robust quantification of relative abundances, providing a
cheap and effective approach for pathogen detection and microbiome profiling on
the MinION system.
PMID- 27485346
TI - Humanizing the zebrafish liver shifts drug metabolic profiles and improves
pharmacokinetics of CYP3A4 substrates.
AB - Understanding and predicting whether new drug candidates will be safe in the
clinic is a critical hurdle in pharmaceutical development, that relies in part on
absorption, distribution, metabolism, excretion and toxicology studies in vivo.
Zebrafish is a relatively new model system for drug metabolism and toxicity
studies, offering whole organism screening coupled with small size and potential
for high-throughput screening. Through toxicity and absorption analyses of a
number of drugs, we find that zebrafish is generally predictive of drug toxicity,
although assay outcomes are influenced by drug lipophilicity which alters drug
uptake. In addition, liver microsome assays reveal specific differences in
metabolism of compounds between human and zebrafish livers, likely resulting from
the divergence of the cytochrome P450 superfamily between species. To reflect
human metabolism more accurately, we generated a transgenic "humanized" zebrafish
line that expresses the major human phase I detoxifying enzyme, CYP3A4, in the
liver. Here, we show that this humanized line shows an elevated metabolism of
CYP3A4-specific substrates compared to wild-type zebrafish. The generation of
this first described humanized zebrafish liver suggests such approaches can
enhance the accuracy of the zebrafish model for toxicity prediction.
PMID- 27485347
TI - Influence of the Time of Intravenous Administration of Paracetamol on its
Pharmacokinetics and Ocular Disposition in Rabbits.
AB - BACKGROUND AND OBJECTIVES: Paracetamol is one of the most common analgesics and
antipyretics applied in health care. The aim of the study was to investigate the
influence of the time-of-day administration on the paracetamol pharmacokinetics
and its penetration into aqueous humour (AH). METHODS: Rabbits were divided into
three groups: I-receiving paracetamol at 08.00 h, II-receiving paracetamol at
16.00 h, and III-receiving paracetamol at 24.00 h. Paracetamol was administered
intravenously at a single dose of 35 mg/kg. The concentrations of paracetamol and
its metabolite (paracetamol glucuronide) in the plasma, as well as in AH were
measured with the validated HPLC-UV method. RESULTS: No significant differences
in the pharmacokinetic parameters of paracetamol was observed. When the drug was
administered at 24.00 h, elimination half-life (t 1/2kel) of paracetamol
glucuronide was longer than when the drug was administered 08.00 h (P = 0.0193).
In addition, a statistically significant increase in the paracetamol
glucuronide/paracetamol ratio was observed when the drug was administered at
08.00 vs. 16.00 h (P <= 0.0001) and 24.00 h (P <= 0.0001). CONCLUSIONS: There was
no chronobiological effect on the pharmacokinetic parameters of paracetamol.
PMID- 27485348
TI - CPP2-p16MIS treatment-induced colon carcinoma cell death in vitro and prolonged
lifespan of tumor-bearing mice.
AB - BACKGROUND: Cell-penetrating peptides (CPPs) are a research hotspot due to their
noninvasive delivery ability. Among the identified CPPs, the TAT and R8 peptides
have been preferentially applied to transduction into different cells. However,
this process is nonselective among various cells. Recent research suggested that
CPP2 could selectively penetrate human colorectal cancer (CRC) cells. METHODS:
Using in vitro experiments, the mean fluorescence intensity of fluorescein
isothiocyanate-labeled CPPs (CPPs-FITC) incubated with different cell lines was
compared to corroborate the colon tumor targeting ability of CPP2. The targeting
ability of CPP2 was determined in the same way in tumor-bearing mice. We
synthesized antitumor peptides by fusing CPP2 to the minimal inhibitory sequence
of p16 (p16MIS), which had the ability to restore the function of lost p16, the
expression of which was absent in tumor cell lines of various origins. The
antitumor effect of the combined peptide was tested in both CRC cell lines and
tumor-bearing mice. RESULTS: In each CRC cell line, the mean fluorescence
intensity of CPP2-FITC was higher than that of the TAT-FITC (p < 0.001) and R8
FITC (p < 0.001) groups. CPP2-p16MIS, the targeting carrier, showed a higher
antitumor response in the in vitro cell research. CPP2-p16MIS showed a prolonged
mean lifespan of tumor-bearing mice, further characterizing its role in specific
tumor-targeting ability in vivo. Survival analysis showed that the mice treated
with CPP2-p16MIS had significantly longer survival than the mice treated with
phosphate-buffered saline (p < 0.05) or those treated with control peptides,
including the CPP2 (p < 0.05) and p16MIS (p < 0.05) groups. CONCLUSION: CPP2
could more selectively penetrate CRC cells than TAT or R8 as well as effectively
deliver the p16MIS to the tumor.
PMID- 27485349
TI - The care center influences the management of lymphoma patients in a universal
health care system: an observational cohort study.
AB - BACKGROUND: Healthcare providers-related disparities in adherence to the
treatment plan among lymphoma patients are found even in a universal healthcare
system, but the mechanism remains unclear. We investigated the association
between the type of care center and the relative dose intensity and determined
whether it persists after adjustment for patients' recruitment differences.
METHODS: Prospective observational cohort study of 294 patients treated with
standard protocols for diffuse large B-cell lymphoma (DLBCL) in teaching or
community public hospitals or in private centers in the French Midi-Pyrenees
region from 2006-2013. To test our assumptions, we used multinomial and mixed
effect logistic models progressively adjusted for patients' biomedical
characteristics, socio-spatial characteristics and treatment-related toxicity
events. RESULTS: Patients treated using standard protocols in the teaching
hospital had more advanced stage and poorer initial prognosis without limitation
regarding the distance from the residence to the care center. Patients'
recruitment profile across the different types of care center failed to explain
the difference in relative dose intensity. Low relative dose intensity was less
often observed in teaching hospital than elsewhere. CONCLUSION: We showed that
even in a universal healthcare system, disparities in the management of DLBCL
patients' do exist according to the types of care center. A main issue may be to
find and diffuse the reasons of this benefit in cancer management in the teaching
hospital to the other centers.
PMID- 27485350
TI - Ireland's contribution to urology and nephrology research in the new millennium:
a bibliometric analysis.
AB - INTRODUCTION: Bibliometrics is the statistical analysis of written publications.
Bibliometric analyses have been performed across a range of biomedical
disciplines. The aim of this study was to provide a comprehensive qualitative and
quantitative analysis of Irish urology and nephrology research and to analyse how
this compares internationally. METHODS: We performed a retrospective bibliometric
analysis of the top 20 ranking journals in the field of "Urology and Nephrology"
based on their 5 years impact factor, as obtained from the ISI Journal Citation
Report database over the 15-year study period, 2000-2015. Utilising the Pubmed
database, a search phrase was constructed using country of affiliation, year of
publication and journal title. The abstracts of the Irish publications identified
were analysed for their institution of origin, article theme and content.
RESULTS: A total of 67,740 article abstracts were analysed over the 15 years
study period. As anticipated, the USA accounted for the largest number of
publications by a country [28,206 (41.64 % of all articles)]. Ireland contributed
347 articles in total (0.51 % of all articles); however, ranking according to
population per million was 13th worldwide. Ireland's contribution to urology and
nephrology research was highest in the BJUI-British Journal of Urology
International [76 articles (21.90 % of Irish total)]. CONCLUSION: We believe this
study to be the largest bibliometric analysis in the field of urology and
nephrology internationally. This study provides a novel overview of the current
Irish urology- and nephrology-related research, and examines how our results
compare within the international community.
PMID- 27485351
TI - Physiological mechanisms of QRS narrowing in bundle branch block patients
undergoing permanent His bundle pacing.
AB - His bundle pacing is increasingly used to avoid chronic right ventricular pacing,
and electrically resynchronize ventricular activation by narrowing or normalizing
the QRS interval in left and right bundle branch block. The mechanisms by which
this occurs remain poorly understood. In this review, the proposed mechanisms and
evidence supporting them are discussed. Also discussed are aspects of mechanisms
that are not completely supported by the evidence. We also review the differences
and physiological bases for direct vs. indirect His bundle capture, and the
physiological mechanisms for QRS narrowing vs. normalization following His bundle
pacing.
PMID- 27485352
TI - Cervical reconstruction techniques. After adequate selection of the patient
report of a series of 34 patients treated with winged expandable cages.
AB - After single or multilevel cervical corpectomy for the treatment of different
diseases, many surgical options have been proposed over the years. As a single
device, a winged expandable titanium cage (WETC) has been developed. We report
the use of this device and our clinical results at 24 months of follow-up in a
prospective series of 34 patients who underwent single or multilevel corpectomy
for the treatment of cervical spondylosis. Thirty-four consecutive patients
underwent single or multilevel cervical corpectomy followed by the insertion of a
WETC for the treatment of cervical spondylosis at Department of Neurology and
Psychiatry "Sapienza" University of Rome, Italy, from May 2011 to May 2013.
Patients affected by cervical spondylosis with cervical lordosis >0 degrees were
included. Patients affected by cervical lordosis <0 degrees , osteoporosis, or
other cervical diseases were excluded. The mean postsurgical Nurick's grade was
significantly lower than the mean presurgical Nurick's grade (mean = 0.98 for
postsurgical Nurick's grade and mean = 2.42 for presurgical Nurick's grade). Four
patients (11.7 %) presented subsidence respectively of 1, 2, 2, and 3 mm at 24
months of radiological follow-up. Postoperative complications occurred in five
patients (14.7 %). Our case series at 24 months of follow-up demonstrates that
the use of a WETC obtains good clinical results after single or multiple
corpectomy in patients not affected by osteoporosis who do not require cervical
lordosis correction. During the insertion of the device, an adequate preparation
of the end plates is suggested and their over distraction should be avoided.
PMID- 27485353
TI - Cellular plasticity: 1712 to the present day.
AB - Cell identity is a fundamental feature of cells. Tissues are often organized into
cellular hierarchies characterized by progressive differentiation and
developmental commitment. However, it is been historically evident that the cells
of many organisms of various phyla, especially in the context of injury, exhibit
remarkable plasticity in terms of their ability to convert into other cell types.
Recent modern studies, using genetic lineage tracing, have demonstrated that many
mature functional cells retain a potential to undergo lineage reversion
(dedifferentiation) or to convert into cells of other more distant lineages
(transdifferentiation) following injury. Similarly, mimicking progenitor cell
transdetermination, stem cells can interconvert. These forms of plasticity may be
essential for organismal survival, and are likely part and parcel of
regeneration.
PMID- 27485355
TI - The Order of Addition of Immunocompromise: The Effects of HIV Infection on
Fibrosis Progression Among Hepatitis C Virus-Infected Patients.
PMID- 27485354
TI - Human ULK1 Variation and Susceptibility to Mycobacterium tuberculosis Infection.
AB - BACKGROUND: Unlike tuberculosis, few studies have evaluated a host genetic basis
for variability in susceptibility to latent Mycobacterium tuberculosis infection
(LTBI). We performed a candidate gene association study of autophagy-related
genes and LTBI. METHODS: We enrolled close contacts of individuals with pulmonary
tuberculosis, assessed LTBI status, and determined clinical and sociodemographic
risk factors for LTBI. In participants who self-identified as Asian or black, we
compared haplotype-tagging single-nucleotide polymorphisms (SNPs) in ULK1 and
GABARAP between cases (n = 143) and controls (n = 106). Using CRISPR/Cas9 in U937
monocytes, we investigated the effect of ULK1 deficiency on cytokine expression,
autophagy, and M. tuberculosis replication. RESULTS: In Asian participants, we
identified 2 ULK1 SNPs (rs12297124 and rs7300908) associated with LTBI. After
adjustment for population admixture and clinical risk for LTBI, each rs12297124
minor allele conferred 80% reduction in LTBI risk (odds ratio, 0.18; 95%
confidence interval, .07-.46). Compared with controls, ULK1-deficient cells
exhibited decreased tumor necrosis factor secretion after stimulation with Toll
like receptor ligands and M. tuberculosis whole-cell lysate, increased M.
tuberculosis replication, and decreased selective autophagy. CONCLUSIONS: These
results demonstrate a strong association of rs12297124, a noncoding ULK1 SNP,
with LTBI and a role for ULK1 regulation of TNF secretion, nonspecific and M.
tuberculosis-induced autophagy, and M. tuberculosis replication in monocytes.
PMID- 27485356
TI - Fibrosis Progression in Patients With Chronic Hepatitis C Virus Infection.
AB - BACKGROUND: Fibrosis progression varies markedly in hepatitis C virus (HCV)
infected individuals. We investigated factors that influence fibrosis progression
in chronic HCV infection. METHODS: HCV-infected patients who underwent at least 2
liver biopsies were included in this study. Associations between fibrosis
progression and epidemiologic, virologic, and disease-associated factors were
analyzed using logistic regression and multistate Markov modeling. RESULTS: We
analyzed 936 biopsy specimens obtained from 378 individuals. Mean age (+/-SD) at
first biopsy was 48.3 +/- 9.3 years, 59.3% of patients were male, 59.9% were
white, and 86.7% were infected with HCV genotype 1. Fibrosis progression and
cirrhosis occurred in 57.4% and 5.8%, respectively. Fibrosis progression between
the first and last biopsies was associated with lower fibrosis in the first
biopsy specimen (P < .001) and with the occurrence of at least 1 flare in the
alanine aminotransferase (ALT) level (>200 U/L; P = .007). We found the highest
fibrosis progression rate between stages 0 and 1 and the lowest between stages 2
and 3. Increased necroinflammation and higher ALT level were associated with
faster progression. HCV genotype 3-infected patients were more likely to progress
to cirrhosis (P < .001). CONCLUSIONS: Fibrosis progression in HCV is not linear
but varies according to stage, with the highest progression in patients with the
lowest fibrosis severity. Patients who experience flares in the ALT level are
also more likely to progress.
PMID- 27485358
TI - Armah et al (J Infect Dis 2016; 213:1678-85).
PMID- 27485359
TI - Surgery for Benign Gynecological Disorders Improve Endometrium Receptivity.
AB - Regardless of the anatomical locations, some benign gynecological disorders
(BGDs) such as peritoneal endometriosis, ovarian endometrioma, adenomyosis,
uterine leiomyomas, endometrial polyps, uterine septum, and hydrosalpinges may
lead to implantation failure. Despite progress in medical therapies, surgery
remains a mainstay of BGDs treatment. Although our knowledge of endometrial
receptivity after BGDs surgery is limited, it has allowed for significant
improvement in the treatment of female subfertility. Many researchers studied on
pregnancy outcome following BGDs surgery, but they did not investigate the
possible impact of surgery on endometrial receptivity. They, therefore, concluded
that pregnancy rates improved after BGDs surgery based on clinical observations.
Many of these clinicians believe that surgical resection of BGDs leads to removal
of local mechanical effect over the endometrium. Moreover, they accept that BGDs
surgery may inhibit the detrimental signaling and secretion of some molecules
from the BGDSs into the endometrium that may lead to favorable effect on the
endometrium. However, so far, data from randomized controlled trials or
systematic review or meta-analyses to answer the question whether surgical
treatment of BGDs can improve endometrial receptivity are lacking. The purpose of
this systematic review was to evaluate the results of available publications
dealing with the impact of reproductive surgery for BGDs on endometrial
receptivity.
PMID- 27485361
TI - Exposure to Zearalenone During Early Pregnancy Causes Estrogenic Multitoxic
Effects in Mice.
AB - Although zearalenone (ZEN; Sigma Chemicals, St Louis, Missouri) is a well-known
mycotoxin with estrogenic activity, the toxic effects of ZEN during pregnancy are
unknown. This study compared the effects of daily subcutaneous injections of ZEN
(2, 4, or 8 mg/kg) with those of 17beta-estradiol (E2; [Sigma Chemicals] 0.8,
1.6, or 3.2 MUg/kg) in mice. Injections were administered on gestational days
(GDs) 1 to 5, the period including implantation which is sensitive to hormonal
balance. The effects of ZEN or E2 were evaluated by comparing the number of live
fetuses, their weight, and absorbed conceptuses on GD 18, with those in vehicle
treated controls. In addition, implantation, embryos in the oviducts and those in
uteri without implantation sites were investigated on GD 5. In mice treated with
the highest dose of ZEN or E2, decidual responses and plasma progesterone
concentrations were measured on GDs 5 and 6, respectively, and delayed
implantation was investigated on GDs 9 and 14. The results showed that treatment
with ZEN, in a manner similar to that seen for E2, led to obstruction of
essential processes for establishing and maintaining pregnancy, such as embryo
migration from oviducts to uteri, the decidual response, and activation of luteal
function. Zearalenone also induced delayed implantation and loss of conceptuses
and at low doses caused a retarded growth of the fetuses after normal
implantation. It was therefore concluded that ZEN causes multiple estrogenic
toxic actions when administered during early pregnancy in mice.
PMID- 27485360
TI - Panel of Autoimmune Markers for Noninvasive Diagnosis of Minimal-Mild
Endometriosis.
AB - Endometriosis, characterized by the presence of endometrial-like tissue at
extrauterine sites, is a common, chronic, estrogen-dependent, inflammatory
condition associated with pelvic pain, subfertility, dysmenorrhea, and
dyspareunia, affecting about 10% of reproductive-age women in any population. The
diagnosis of endometriosis is usually delayed on an average by 8 to 11 years
leading to significant consequences in terms of disease progression. The current
study was aimed to validate enzyme-linked immunosorbent assay based on the
epitopes of stomatin-like protein 2, tropomodulin 3 (TMOD3), and tropomyosin 3
(TPM3) for diagnosis of minimal-mild endometriosis (revised American Fertility
Society Classification (rAFS) stage I-II) and to compare the performance with the
reported markers: cancer antigen (CA) 125, CA19-9, alpha-enolase,
Serine/threonine-protein kinase (PDIK1L), and syntaxin 5. This was a cross
sectional, multicenter study conducted during the year 2012 to 2015. Women with
minimal-mild endometriosis (rAFS stage I-II [n = 133]) and healthy controls (n =
104) were screened for 11 novel autoimmune markers and reported markers alpha
enolase, PDIK1L, syntaxin 5, CA-125, and CA19-9. The sensitivity and diagnostic
accuracy of serum antibodies against all the 11 epitopes were higher than that of
CA-125, CA19-9, alpha-enolase, PDIK1L, and syntaxin 5 for diagnosis of rAFS stage
I to II endometriosis. The sensitivity of 6 biomarkers (anti-TMOD3b-autoAb, anti
TMOD3c-autoAb, anti-TMOD3d-autoAb, anti-TPM3a-autoAb, anti-TPM3c-autoAb, and anti
TPM3d-autoAb) was higher at the specificity of >=80% for diagnosis of rAFS stage
I to II endometriosis as well as ultrasound-negative endometriosis. Further,
logistic regression models of this panel of biomarkers showed increase in
sensitivity, specificity, and diagnostic accuracy than individual biomarkers. The
panel of 6 autoimmune biomarkers could be useful in setting up of noninvasive
diagnostic test for detection of minimal-mild endometriosis.
PMID- 27485362
TI - Ultrasound-Assisted Catheter-Directed Thrombolysis in High-Risk and Intermediate
High-Risk Pulmonary Embolism: Results From a Single-Center Cohort.
AB - We present our single-center results on ultrasound-assisted thrombolysis (USAT)
in patients with pulmonary embolism (PE) at intermediate high risk (IHR) and high
risk (HR). Our study consisted of 75 patients with PE who underwent USAT (60 at
IHR and 15 at HR). The median time delay from symptoms to USAT was 5 days.
Ultrasound-assisted thrombolysis resulted in improvements in tricuspid annular
plane systolic excursion; pulmonary artery (PA) systolic and mean pressures;
Qanadli score; right to left ventricle diameter ratio and right to left atrial
diameter ratio; and diameters of main, right, and left PA regardless of the
baseline risk status ( P < .0001 for all). Death was documented in 4 patients,
and major and minor bleeding were noted in 2 and 5 of the patients, respectively.
No PE-related event was noted during postdischarge follow-up period of median 310
days. Our study revealed that USAT facilitates the resolution of PA thrombotic
burden, recovery of pulmonary hemodynamics, and right heart functions with
acceptable rates of procedure-related complications in patients with PE,
irrespective of the IHR or HR status.
PMID- 27485357
TI - Renal Impairment and Cardiovascular Disease in HIV-Positive Individuals: The
D:A:D Study.
AB - BACKGROUND: While the association between renal impairment and cardiovascular
disease (CVD) is well established in the general population, the association
remains poorly understood in human immunodeficiency virus (HIV)-positive
individuals. METHODS: Individuals with >=2 estimated glomerular filtration rate
(eGFR) measurements after 1 February 2004 were followed until CVD, death, last
visit plus 6 months, or 1 February 2015. CVD was defined as the occurrence of
centrally validated myocardial infarction, stroke, invasive cardiovascular
procedures, or sudden cardiac death. RESULTS: During a median follow-up duration
of 8.0 years (interquartile range, 5.4-8.9 years) 1357 of 35 357 individuals
developed CVD (incidence rate, 5.2 cases/1000 person-years [95% confidence
interval {CI}, 5.0-5.5]). Confirmed baseline eGFR and CVD were closely related
with 1.8% of individuals (95% CI, 1.6%-2.0%) with an eGFR > 90 mL/minute/1.73
m(2) estimated to develop CVD at 5 years, increasing to 21.1% (95% CI, 6.6%
35.6%) among those with an eGFR <= 30 mL/minute/1.73 m(2) The strong univariate
relationship between low current eGFR and CVD was primarily explained by
increasing age in adjusted analyses, although all eGFRs <= 80 mL/minute/1.73 m(2)
remained associated with 30%-40% increased CVD rates, and particularly high CVD
rates among individuals with an eGFR <= 30 mL/minute/1.73 m(2) (incidence rate
ratio, 3.08 [95% CI, 2.04-4.65]). CONCLUSIONS: Among HIV-positive individuals in
a large contemporary cohort, a strong relation between confirmed impaired eGFR
and CVD was observed. This finding highlights the need for renal preventive
measures and intensified monitoring for emerging CVD, particularly in older
individuals with continuously low eGFRs.
PMID- 27485363
TI - Strategies Preventing Contrast-Induced Nephropathy After Coronary Angiography: A
Comprehensive Meta-Analysis and Systematic Review of 125 Randomized Controlled
Trials.
AB - This systematic review with meta-analysis sought to determine the strength of
evidence for the effects of hydration (sodium bicarbonate [SB] and normal saline
[NS]), supplementations ( N-acetylcysteine [NAC] and vitamin C), and some common
drugs (adenosine antagonists [AAs], statins, loop diuretics, and angiotensin
converting enzyme inhibitors [ACEIs]) on the incidence of contrast-induced
nephropathy (CIN) and requirement for hemodialysis after coronary angiography.
After screening, a total of 125 trials that reported outcomes were identified.
Pooled analysis indicated beneficial effects of SB versus NS (odds ratio [OR] =
0.73; 95% confidence interval [CI]: 0.56-0.94; P = .01), NAC (OR = 0.79; 95% CI:
0.70-0.88; P = .001), vitamin C (OR = 0.64; 95% CI: 0.45-0.89; P = .01), statins
(OR = 0.45; 95% CI: 0.35-0.57; P = .001), AA (OR = 0.28; 95% CI: 0.14-0.47; P =
.001), loop diuretics (OR = 0.97; 95% CI: 0.33-2.85; P = .9), and ACEI (OR =
1.06; 95% CI: 0.69-1.61; P = .8). Overall, hydration with SB, use of supplements,
such as NAC and vitamin C, and administration of statins and AA should always be
considered for the prevention of CIN after coronary angiography.
PMID- 27485364
TI - Patient and Therapist Agreement on Performance-Rated Ability Using the de Morton
Mobility Index.
AB - OBJECTIVE: To determine the level of agreement between patient self-report and
therapist-assessed performance of mobility using the de Morton Mobility Index
(DEMMI). DESIGN: Interrater agreement study. SETTING: Outpatient hospital clinic.
PARTICIPANTS: Consecutive sample of patients (N=128) undergoing preoperative
assessment for elective lower limb (LL) arthroplasty. INTERVENTIONS: Participants
completed a therapist-directed assessment of the DEMMI followed by self-report of
performance. A random subsample (n=62, 48%) also completed a self-report of
anticipated performance before the therapist-directed assessment. Both raters
(participant and therapist) were blinded to the scores obtained from the other
rater. MAIN OUTCOME MEASURES: Interrater agreement between patient self-report
and therapist-directed assessment of the total DEMMI scores was assessed using
the intraclass correlation coefficient model 2,1 (ICC2,1) with a 95% confidence
interval. The Bland-Altman plots were also used to illustrate the agreement
between the 2 raters. RESULTS: The intraclass correlation coefficient (ICC)
between patient self-report after performance and therapist-directed assessment
of the total DEMMI score was .967 (95% confidence interval, .952-.977). The ICC
between patient self-report of anticipated performance and therapist-directed
assessment of the total DEMMI score was .830 (95% confidence interval, .730
.894). The Bland-Altman plots depicted higher levels of agreement among
participants with impaired levels of mobility (<=74 out of 100) than did those
with near-maximum DEMMI scores. CONCLUSIONS: Patient self-report of anticipated
performance is an acceptable proxy for DEMMI scores derived from the therapist
rating of performance. Caution should be exercised when interpreting self-report
scores of patients with near-maximum levels of mobility. Further research is
required to establish whether these results can be generalized across a range of
patient populations and to clinicians with differing backgrounds and expertise.
PMID- 27485365
TI - Social Isolation and Physical Barriers in the Houses of Stroke Survivors in Rural
China.
AB - OBJECTIVE: To describe the home barriers and social isolation of stroke survivors
in the rural areas of China and to explore which home barriers are associated
with social isolation. DESIGN: Cross-sectional survey. SETTING: Structured
interviews and observation in the participants' homes. PARTICIPANTS: Community
dwelling stroke survivors in the rural areas of China (N=818). INTERVENTIONS: Not
applicable. MAIN OUTCOME MEASURES: Physical barriers in rural homes were surveyed
using a home fall hazards assessment. Social isolation was identified if >=2 of
the following indicators were observed: low frequency of getting out of the home,
lacking leisure activities, and living alone in the previous 3 months. RESULTS:
The prevalence rates of 18 among 30 home barriers were >20%, and the highest was
93% (lack of handrails in the bathroom). The prevalence of social isolation was
30%. Three home barriers were independently related to social isolation. These
were a distant toilet (odds ratio [OR], 2.363; 95% confidence interval [CI],
1.527-3.658; P<.001), unsuitable seating (OR, 1.571; 95% CI, 1.026-2.404;
P=.038), and inaccessible light switches (OR, 1.572; 95% CI, 1.064-2.324;
P=.023). CONCLUSIONS: Many barriers exist in the houses of stroke survivors in
rural China. Some of them are related to social isolation. Eliminating or
decreasing home barriers could be a feasible and effective approach to reducing
social isolation.
PMID- 27485366
TI - Gait Retraining With Real-Time Biofeedback to Reduce Knee Adduction Moment:
Systematic Review of Effects and Methods Used.
AB - OBJECTIVE: To review the current literature regarding methods and effects of real
time biofeedback used as a method for gait retraining to reduce knee adduction
moment (KAM), with intended application for patients with knee osteoarthritis
(KOA). DATA SOURCES: Searches were conducted in MEDLINE, Embase, CINAHL,
SPORTDiscus, Web of Science, and Cochrane Central Register of Controlled Trials
with the keywords gait, feedback, and knee osteoarthritis from inception to May
2015. STUDY SELECTION: Titles and abstracts were screened by 1 individual for
studies aiming to reduce KAM. Full-text articles were assessed by 2 individuals
against predefined criteria. DATA EXTRACTION: Data were extracted by 1 individual
according to a predefined list, including participant demographics and training
methods and effects. DATA SYNTHESIS: Electronic searches resulted in 190
potentially eligible studies, from which 12 met all inclusion criteria. Within
group standardized mean differences (SMDs) for reduction of KAM in healthy
controls ranged from .44 to 2.47 and from .29 to .37 in patients with KOA. In
patients with KOA, improvements were reported in pain and function, with SMDs
ranging from .55 to 1.16. Methods of implementation of biofeedback training
varied between studies, but in healthy controls increased KAM reduction was noted
with implicit, rather than explicit, instructions. CONCLUSIONS: This review
suggests that biofeedback gait training is effective primarily for reducing KAM
but also for reducing pain and improving function in patients with KOA. The
review was limited by the small number of studies featuring patients with KOA and
the lack of controlled studies. The results suggest there is value and a need in
further researching biofeedback training for reducing KAM. Future studies should
include larger cohorts of patients, long-term follow-up, and controlled trials.
PMID- 27485367
TI - Novel method using 3-dimensional segmentation in spectral domain-optical
coherence tomography imaging in the chick reveals defocus-induced regional and
time-sensitive asymmetries in the choroidal thickness.
AB - Studies into the mechanisms underlying the active emmetropization process by
which neonatal refractive errors are corrected, have described rapid,
compensatory changes in the thickness of the choroidal layer in response to
imposed optical defocus. While high frequency A-scan ultrasonography, as
traditionally used to characterize such changes, offers good resolution of
central (on-axis) changes, evidence of local retinal control mechanisms make it
imperative that more peripheral, off-axis changes also be tracked. In this study,
we used in vivo high resolution spectral domain-optical coherence tomography (SD
OCT) imaging in combination with the Iowa Reference Algorithms for 3-dimensional
segmentation, to more fully characterize these changes, both spatially and
temporally, in young, 7-day old chicks (n = 15), which were fitted with monocular
+15 D defocusing lenses to induce choroidal thickening. With these tools, we were
also able to localize the retinal area centralis, which was used as a landmark
along with the ocular pectin in standardizing the location of scans and aligning
them for subsequent analyses of choroidal thickness (CT) changes across time and
between eyes. Values were derived for each of four quadrants, centered on the
area centralis, and global CT values were also derived for all eyes. Data were
compared with on-axis changes measured using ultrasonography. There were
significant on-axis choroidal thickening that was detected after just one day of
lens wear (~190 um), and regional (quadrant-related) differences in choroidal
responses were also found, as well as global thickness changes 1 day after
treatment. The ratio of global to on-axis choroidal thicknesses, used as an index
of regional variability in responses, was also found to change significantly,
reflecting the significant central changes. In summary, we demonstrated in vivo
high resolution SD-OCT imaging, used in combination with segmentation algorithms,
to be a viable and informative approach for characterizing regional (spatial),
time-sensitive changes in CT in small animals such as the chick.
PMID- 27485368
TI - Comparison of results of graft uptake using tragal cartilage perichondrium
composite graft versus temporalis fascia in patients undergoing surgery for
chronic otitis media - squamous type.
AB - BACKGROUND: To assess, analyze and compare the results of graft uptake using
Tragal Cartilage-Perichondrium Composite (TCPC) graft with Temporalis Fascia (TF)
graft in patients who undergoing surgery for chronic otitis media - squamous
type. METHODS: Patients aged 13 years and above with diagnosis of chronic otitis
media - squamous type undergoing modified radical mastoidectomy, either primary
or revision surgery with grafting of tympanic membrane (TM) and patients
undergoing excision of postero-superior retraction pocket (PSRP) were included in
this study. Patients were divided in two groups: Group A-patients undergoing TCPC
graft and Group B -patients undergoing TF graft. Graft uptake results were
assessed between 8-12 weeks of surgery. RESULTS: In both Groups there were 30
patients each. In Group A successful graft uptake was seen in 27 patients (90 %)
and failure of graft uptake was seen in 3 patients(10 %). In Group B successful
graft uptake was seen in 28 patients (93.3 %) and failure in 2 patients (6.67
%).Out of the total 60 patients, 11 patients had PSRP. All 6 patients with PSRP
in Group A had successful graft uptake and no retraction. Among the 5 patients
with PSRP in Group B all patients had sucessful graft uptake, however, in 2
patients retraction of the tympanic membrane was seen similar to the preoperative
findings. CONCLUSIONS: There was no statistical difference (p = 0.433) between
the use of temporalis fascia or tragal cartilage perichondrium in patients
undergoing surgery for chronic otitis media - squamous type.
PMID- 27485369
TI - Variant origin and course of left circumflex coronary artery.
AB - Variant origin of left circumflex coronary artery (LCx) from right aortic sinus
is a well-recognized coronary variation, usually without any clinical
consequences. However, the variant origin and trajectory of the artery may have
major implications during percutaneous coronary intervention, coronary artery
surgery, aortic and mitral valve replacement procedures. We observed a variant
LCx in a heart specimen belonging to 45-year-female with no history of
hypertension, diabetes mellitus and coronary artery disease. The artery arose
along with the right coronary artery from a common ostium in right aortic sinus
and depicted a retroaortic course. The vessel was located at the level of aortic
annulus and 6.6 mm above mitral valve annulus. The degree of luminal stenosis in
variant LCx was higher than that in right coronary artery (RCA) and left anterior
descending artery (LAD). Appropriate anatomical knowledge of the location and
course of variant LCx is important for successful coronary interventions and
valve replacement procedures.
PMID- 27485370
TI - 3D spin-flop transition in enhanced 2D layered structure single crystalline
TlCo2Se2.
AB - The enhanced 2D layered structure single crystalline TlCo2Se2 has been
successfully fabricated, which exhibits field-induced 3D spin-flop phase
transitions. In the case of the magnetic field parallel to the c-axis (B//c), the
applied magnetic field induces the evolution of the noncollinear helical magnetic
coupling into a ferromagnetic (FM) state with all the magnetization of the Co ion
parallel to the c-axis. A striking variation of the field-induced strain within
the ab-plane is noticed in the magnetic field region of 20-30 T. In the case of
the magnetic field perpendicular to the c-axis (B ? c), the inter-layer helical
antiferromagnetic (AFM) coupling may transform to an initial canted AFM coupling,
and then part of it transforms to an intermediate metamagnetic phase with the
alignment of two-up-one-down Co magnetic moments and finally to an ultimate FM
coupling in higher magnetic fields. The robust noncollinear AFM magnetic coupling
is completely destroyed above 30 T. In combination with the measurements of
magnetization, magnetoresistance and field-induced strain, a complete magnetic
phase diagram of the TlCo2Se2 single crystal has been depicted, demonstrating
complex magnetic structures even though the crystal geometry itself gives no
indication of the magnetic frustration.
PMID- 27485371
TI - Biological effects of compressive forces exerted on particulate bone grafts
during socket preservation: animal study.
AB - OBJECTIVES: To compare different compressive forces exerted on a particulate
graft material during socket preservation and their effects on bone regeneration.
MATERIAL AND METHODS: Six male dogs were used. The second, third, and fourth
premolars, and the first molar were extracted bilaterally at the lower jaws. A
particulate synthetic biphasic grafting material (60% HA and 40% beta-tricalcium
phosphate) was used. Three different standardized compressive forces were applied
randomly during the socket preservation. The sample was divided into four
experimental groups Test A (10 g), Test B (50 g), Test C (200 g), and Control
(empty sockets). Collagen membranes were placed, and primary closure was
obtained. Two months after the surgery the animals were sacrificed, and
histomorphometric analysis of non-decalcified samples was performed at the
coronal, middle, and apical thirds. RESULTS: Grafted sockets resulted in higher
bony contour (3 +/- 0.43 mm2 ; P < 0.05). The particles penetrated up to the
apical third in the group C but not in the other test groups and controls (P <
0.05). The percentage of new bone were higher at the coronal and apical thirds
for Controls and group C compared to A and B groups (P < 0.05). The residual
graft was higher for group C (53 +/- 1.4%), followed by group B (45 +/- 3.1%) and
group A (35 +/- 1.9%; P < 0.05). The percentages of connective tissue were higher
at the middle third without differences between groups (P > 0.05). CONCLUSIONS:
Within the limitations of this experimental animal study, it might be concluded
that grafted sockets compressed with 200 g force will have higher bony contours;
higher compressive forces facilitate the penetration of the particulate graft
material into the apical area of the socket and results in more bone formation at
the coronal, middle, and apical thirds.
PMID- 27485373
TI - Effect of cadmium on phenolic compounds, antioxidant enzyme activity and
oxidative stress in blueberry (Vaccinium corymbosum L.) plantlets grown in vitro.
AB - Cadmium (Cd(2+)) can affect plant growth due to its mobility and toxicity. We
evaluated the effects of Cd(2+) on the production of phenolic compounds and
antioxidant response of Vaccinium corymbosum L. Plantlets were exposed to Cd(2+)
at 50 and 100uM for 7, 14 and 21 days. Accumulation of malondialdehyde (MDA),
hydrogen peroxide (H2O2) and the antioxidant enzyme SOD was determined. The
profile of phenolic compounds was evaluated using LC-MS. The antioxidant activity
was measured using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the ferric reducing
antioxidant power test (FRAP). Cd(2+) increased the content of MDA, with the
highest increase at 14 days. The presence of Cd(2+) resulted in changes in
phenolic compounds. The main phenolic compound found in blueberry plantlets was
chlorogenic acid, whose abundance increased with the addition of Cd(2+) to the
medium. The changes in the composition of phenolic compounds showed a positive
correlation with the antioxidant activity measured using FRAP. Our results
suggest that blueberry plantlets produced phenolic compounds with reducing
capacity as a selective mechanism triggered by the highest activity of Cd(2+).
PMID- 27485372
TI - Prevalence of Sexual Aggression Victimization and Perpetration in a Sample of
Female and Male College Students in Turkey.
AB - In Turkey, there is a shortage of studies on the prevalence of sexual aggression
among young adults. The present study examined sexual aggression victimization
and perpetration since the age of 15 in a convenience sample of N = 1,376 college
students (886 women) from four public universities in Ankara, Turkey. Prevalence
rates for different coercive strategies, victim-perpetrator constellations, and
sexual acts were measured with a Turkish version of the Sexual Aggression and
Victimization Scale (SAV-S). Overall, 77.6% of women and 65.5% of men reported at
least one instance of sexual aggression victimization, and 28.9% of men and 14.2%
of women reported at least one instance of sexual aggression perpetration.
Prevalence rates of sexual aggression victimization and perpetration were highest
for current or former partners, followed by acquaintances/friends and strangers.
Alcohol was involved in a substantial proportion of the reported incidents. The
findings are the first to provide systematic evidence on sexual aggression
perpetration and victimization among college students in Turkey, including both
women and men.
PMID- 27485374
TI - Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells
through ROS elevation and MRP1 downregulation.
AB - BACKGROUND: Chemoresistance is one of the most leading causes for tumor
progression and recurrence of bladder cancer. Reactive oxygen species (ROS) plays
a key role in the chemosensitivity of cancer cells. In the present study, emodin
(1,3,8-trihydroxy-6-methylanthraquinone) was applied as a ROS generator in
combination with cisplatin in T24 and J82 human bladder cancer cells. METHODS:
Cell viability and apoptosis rate of different treatment groups were detected by
3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and flow
cytometry (FCM). The expression of transporters was measured at both the
transcription and translation levels using PCR and western blotting. In vitro
findings were confirmed by in vivo experiments using tumor-bearing mice. The
expression of multidrug resistance-associated protein 1 (MRP1) in tumour tissue
was measured using immunohistochemistry and side effects of the emodin/cisplatin
co-treatment were investigated by histological examination. RESULTS: Emodin
increased the cellular ROS level and effectively enhanced the cisplatin-induced
cytotoxicity of T24 and J82 human bladder cancer cells through decreasing
glutathione-cisplatin (GSH-cisplatin) conjugates. It blocked the chemoresistance
of T24 and J82 cells to cisplatin through suppressing the expression of MRP1.
This effect was specific in T24 and J82 cells but not in HCV-29 normal bladder
epithelial cells. Consistent with in vitro experiments, emodin/cisplatin co
treatment increased the cell apoptosis and repressed the MRP1 expression in
xenograft tumors, and without obvious systemic toxicity. CONCLUSIONS: This study
revealed that emodin could increase the cisplatin-induced cytotoxicity against
T24 and J82 cells via elevating the cellular ROS level and downregulating MRP1
expression. We suggest that emodin could serve as an effective adjuvant agent for
the cisplatin-based chemotherapy of bladder cancer.
PMID- 27485375
TI - Assessing treatment barriers in eating disorders: A systematic review.
AB - This systematic review evaluated methods used to assess treatment barriers among
individuals with eating disorders or disordered eating. A total of 11 studies
were identified and evaluated according to attributes considered important in the
accurate assessment of treatment barriers. The majority of studies used
qualitative methods, with five studies utilizing either a checklist or scale
based instrument. Adequate psychometric investigation was lacking. This review
highlights the paucity of research examining barriers to accessing and/or
receiving treatment in disordered eating populations. There is a need for
development of psychometrically sound instruments that assess the range and
relative interference of specific barriers experienced in this population.
PMID- 27485376
TI - A role for Rtt109 in buffering gene-dosage imbalance during DNA replication.
AB - Chromatin can function as an integrator of DNA-related processes, allowing
communication, for example, between DNA replication and gene transcription. Such
communication is needed to overcome the gene-dosage imbalance introduced during
DNA replication, when certain genes are replicated prior to others. Increased
transcription of early replicating genes could alter regulatory balances. This
does not occur, suggesting a mechanism that suppresses expression from newly
replicated DNA. Critical to this buffering is Rtt109, which acetylates the
internal K56 residue of newly synthesized histone H3 prior to incorporation onto
DNA. H3K56ac distinguishes replicated from non-replicated DNA, communicating this
information to the transcription machinery to ensure expression homeostasis
during S phase.
PMID- 27485377
TI - Bayesian adaptive patient enrollment restriction to identify a sensitive
subpopulation using a continuous biomarker in a randomized phase 2 trial.
AB - With the development of molecular targeted drugs, predictive biomarkers have
played an increasingly important role in identifying patients who are likely to
receive clinically meaningful benefits from experimental drugs (i.e., sensitive
subpopulation) even in early clinical trials. For continuous biomarkers, such as
mRNA levels, it is challenging to determine cutoff value for the sensitive
subpopulation, and widely accepted study designs and statistical approaches are
not currently available. In this paper, we propose the Bayesian adaptive patient
enrollment restriction (BAPER) approach to identify the sensitive subpopulation
while restricting enrollment of patients from the insensitive subpopulation based
on the results of interim analyses, in a randomized phase 2 trial with time-to
endpoint outcome and a single biomarker. Applying a four-parameter change-point
model to the relationship between the biomarker and hazard ratio, we calculate
the posterior distribution of the cutoff value that exhibits the target hazard
ratio and use it for the restriction of the enrollment and the identification of
the sensitive subpopulation. We also consider interim monitoring rules for
termination because of futility or efficacy. Extensive simulations demonstrated
that our proposed approach reduced the number of enrolled patients from the
insensitive subpopulation, relative to an approach with no enrollment
restriction, without reducing the likelihood of a correct decision for next trial
(no-go, go with entire population, or go with sensitive subpopulation) or correct
identification of the sensitive subpopulation. Additionally, the four-parameter
change-point model had a better performance over a wide range of simulation
scenarios than a commonly used dichotomization approach. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27485378
TI - Vigabatrin efficacy in GPR56-associated polymicrogyria: The role of GABAA
receptor pathway.
PMID- 27485379
TI - Commentary on clinical significance of CYP2C9-status-guided valproic acid therapy
in children.
PMID- 27485380
TI - In response: Commentary on clinical significance of CYP2C9-status-guided valproic
acid therapy in children.
PMID- 27485381
TI - RT-qPCR for the diagnosis of dermatophilosis in horses.
AB - BACKGROUND: Dermatophilus congolensis causes a crusting dermatitis that affects
horses. Diagnosis requires the identification of the organism with cytological
evaluation of crust samples. This method can lack sensitivity in chronic cases.
HYPOTHESIS/OBJECTIVES: To develop a probe-based real time quantitative polymerase
chain reaction (RT-qPCR) test to assist with the diagnosis of dermatophilosis in
horses. ANIMALS: Twenty six privately owned horses and seven horses from a
research colony were used. METHODS: Crust samples, collected from 14 horses with
suspected dermatophilosis and 12 horses with crusting skin disease not
characteristic of dermatophilosis, were evaluated by cytological evaluation and
RT-qPCR; the latter was also performed on hair samples collected from seven
healthy horses. RESULTS: Cytological evaluation revealed organisms consistent
with Dermatophilus congolensis from nine horses with suspected dermatophilosis,
with only a few organisms seen from five samples. Cytological evaluation of all
other crusts was negative for Dermatophilus. Other bacterial organisms were
detected on cytological evaluation from 15 samples. RT-qPCR for Dermatophilus was
positive from 11 crusts, whereas all other samples were negative. Two samples
were cytologically negative but RT-qPCR positive for Dermatophilus. No samples
were cytologically positive but RT-qPCR negative for Dermatophilus. CONCLUSION:
Results of this study show that RT-qPCR may be a more sensitive and easier method
than cytological evaluation for the diagnosis of dermatophilosis in horses.
PMID- 27485382
TI - Effect of SO2 and steam on CO2 capture performance of biomass-templated calcium
aluminate pellets.
AB - Four types of synthetic sorbents were developed for high-temperature post
combustion calcium looping CO2 capture using Longcal limestone. Pellets were
prepared with: lime and cement (LC); lime and flour (LF); lime, cement and flour
(LCF); and lime, cement and flour doped with seawater (LCFSW). Flour was used as
a templating material. All samples underwent 20 cycles in a TGA under two
different calcination conditions. Moreover, the prepared sorbents were tested for
10 carbonation/calcination cycles in a 68 mm-internal-diameter bubbling fluidized
bed (BFB) in three environments: with no sulphur and no steam; in the presence of
sulphur; and with steam. When compared to limestone, all the synthetic sorbents
exhibited enhanced CO2 capture performance in the BFB experiments, with the
exception of the sample doped with seawater. In the BFB tests, the addition of
cement binder during the pelletisation process resulted in the increase of CO2
capture capacity from 0.08 g CO2 per g sorbent (LF) to 0.15 g CO2 per g sorbent
(LCF) by the 10th cycle. The CO2 uptake in the presence of SO2 dramatically
declined by the 10th cycle; for example, from 0.22 g CO2 per g sorbent to 0.05 g
CO2 per g sorbent in the case of the untemplated material (LC). However, as
expected all samples showed improved performance in the presence of steam, and
the decay of reactivity during the cycles was less pronounced. Nevertheless, in
the BFB environment, the templated pellets showed poorer CO2 capture performance.
This is presumably because of material loss due to attrition under the FB
conditions. By contrast, the templated materials performed better than
untemplated materials under TGA conditions. This indicates that the reduction of
attrition is critical when employing templated materials in realistic systems
with FB reactors.
PMID- 27485383
TI - Direct and quantitative evaluation of the human CYP3A4 contribution (fm) to drug
clearance using the in vitro SILENSOMES model.
AB - 1. Among the different in vitro studies recommended by the regulatory agencies,
no gold-standard model can easily and directly measure the quantitative CYP450
contributions to drug biotransformation. In this article, we propose an original
strategy, called SilensomesTM, to produce human liver microsomes silenced for one
specific CYP450, thanks to specific mechanism-based inhibitors (MBI). 2. Using
azamulin as a specific CYP3A4 MBI, we demonstrated the proof of concept that
CYP3A4 can be totally, specifically (even against 3A5) and permanently (at least
for six years) inhibited by our process. Thus, comparing clearance in control and
CYP3A4-SilensomesTM, CYP3A4 contributions were determined for 11 CYP3A4
substrates which correlated with known in vivo contributions and revealed
accuracy with less than 10% error. In comparison, contributions determined using
recombinant human CYP450 (rhCYP450s) were less accurate (more than 10% error for
30% of the tested CYP3A4 substrates). 3. This easy and ready-to-use in vitro
method combines the advantages of existing models (specificity of rhCYP450s and
representativeness of HLM) without their drawbacks. The same strategy could be
used to silence other major CYP450s one-by-one to provide a complete direct
CYP450 quantitative phenotyping kit.
PMID- 27485384
TI - Loss of coxsackie and adenovirus receptor expression in human colorectal cancer:
A potential impact on the efficacy of adenovirus-mediated gene therapy in Chinese
Han population.
AB - The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and
critical factor for the efficacy of therapeutic strategies that employ the
adenovirus. However, data on CAR expression levels in colorectal cancer are
conflicting and its clinical relevance remains to be elucidated.
Immunohistochemistry was performed on tissue microarrays containing 251 pairs of
colon cancer and adjacent normal tissue samples from Chinese Han patients to
assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR
expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples.
The CAR immunopositivity in tumor tissues was not significantly associated with
gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or
distant metastasis in patients with colon cancer. However, expression of CAR is
present in 83.3% of the tumor tissues from patient with colorectal liver
metastasis, which was significantly higher than those without liver metastasis
(39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa
samples, which was significantly higher than in colorectal cancer samples (4.0%;
P<0.001). In addition, the survival analysis demonstrated that the expression
level of CAR has no association with the prognosis of colorectal cancer. CAR
expression was observed to be downregulated in colorectal cancer, and it exerts
complex effects during colorectal carcinogenesis, potentially depending on the
stage of the cancer development and progression. High CAR expression may promote
liver metastasis. With regard to oncolytic therapy, CAR expression analysis
should be performed prior to adenoviral oncolytic treatment to stratify Chinese
Han patients for treatment.
PMID- 27485385
TI - A two-step strategy for the preparation of 6-deoxy-l-sorbose.
AB - A two-step enzymatic strategy for the efficient and convenient synthesis of 6
deoxy-l-sorbose was reported herein. In the first reaction step, the
isomerization of l-fucose (6-deoxy-l-galactose) to l-fuculose (6-deoxy-l
tagatose) catalyzed by l-fucose isomerase (FucI), and the epimerization of l
fuculose to 6-deoxy-l-sorbose catalyzed by d-tagatose 3-epimerase (DTE) were
coupled with the targeted phosphorylation of 6-deoxy-l-sorbose by fructose kinase
from human (HK) in a one-pot reaction. The resultant 6-deoxy-l-sorbose 1
phosphate was purified by silver nitrate precipitation method. In the second
reaction step, the phosphate group of the 6-deoxy-l-sorbose 1-phosphate was
hydrolyzed with acid phosphatase (AphA) to produce 6-deoxy-l-sorbose in 81% yield
with regard to l-fucose.
PMID- 27485386
TI - New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile
as a non-traditional replacement for heavy halogen atoms.
AB - A number of new nucleoside derivatives are disclosed as inhibitors of DOT1L
activity. SARs established that DOT1L inhibition could be achieved through
incorporation of polar groups and small heterocycles at the 5-position (5, 6, 12)
or by the application of alternative nitrogenous bases (18). Based on these
results, CN-SAH (19) was identified as a potent and selective inhibitor of DOT1L
activity where the polar 5-nitrile group was shown by crystallography to bind in
the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group
can be used as a non-traditional replacement for heavy halogen atoms.
PMID- 27485387
TI - Cloning, expression, purification and sulfonamide inhibition profile of the
complete domain of the eta-carbonic anhydrase from Plasmodium falciparum.
AB - We report the cloning, purification and characterization of the full domain of
carbonic anhydrase (CA, EC 4.2.1.1) from Plasmodium falciparum, which
incorporates 358 amino acid residues (from 181 to 538, in the sequence of this
600 amino acid long protein), called PfCAdom. The enzyme, which belongs to the
eta-CA class showed the following kinetic parameters: kcat of 3.8*10(5)s(-1) and
kcat/Km of 7.2*10(7)M(-1)*s(-1), being 13.3 times more effective as a catalyst
compared to the truncated form PfCA. PfCAdom is more effective than the human (h)
isoform hCA I, being around 50% less effective compared to hCA II, one of the
most catalytically efficient enzymes known so far. Intriguingly, the sulfonamides
CA inhibitors generally showed much weaker inhibitory activity against PfCAdom
compared to PfCA, prompting us to hypothesize that the 69 amino acid residues
insertion present in the active site of this eta-CA is crucial for the active
site architecture. The best sulfonamide inhibitors for PfCAdom were
acetazolamide, methazolamide, metanilamide and sulfanilamide, with KIs in the
range of 366-808nM.
PMID- 27485388
TI - Unraveling gene function in agricultural species using gene co-expression
networks.
AB - Co-expression networks have been shown to be a powerful tool for inferring a
gene's function when little is known about it. With the advent of next generation
sequencing technologies, the construction and analysis of co-expression networks
is now possible in non-model species, including those with agricultural
importance. Here, we review fundamental concepts in the construction and
application of co-expression networks with a focus on agricultural crops. We
survey past and current applications of co-expression network analysis in several
agricultural species and provide perspective on important considerations that
arise when analyzing network relationships. We conclude with a perspective on
future directions and potential challenges of utilizing this powerful approach in
crops. This article is part of a Special Issue entitled: Plant Gene Regulatory
Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.
PMID- 27485389
TI - Effect of clonazepam and clonidine on primary sleep bruxism: a double-blind,
crossover, placebo-controlled trial.
AB - The aim of this study was to assess the acute effects of clonazepam and clonidine
on rhythmic masticatory muscle activity in young adults with primary sleep
bruxism, as well as accompanying effects on sleep architecture and cardiac
activity. This study used a double-blind, crossover, placebo-controlled design.
Polysomnography was performed on 19 subjects [nine men and 10 women; mean age (+/
SE): 25.4 +/- 2.7 years] for 5 nights. The first 2 nights were used for the
habituation and diagnosis of sleep bruxism. The other 3 nights were randomly
assigned for clonazepam (1.0 mg), clonidine (0.15 mg) or placebo (all
administered 30 min before bedtime). Sleep, oromotor activity and cardiac
activity variables were assessed and compared among the three drug conditions.
Clonidine significantly reduced the median percentage of time spent in the rapid
eye movement sleep stage compared with placebo and clonazepam. The number of
rhythmic masticatory muscle activity episodes was reduced with clonidine by >30%
compared with placebo and clonazepam. The reduction of rhythmic masticatory
muscle activity index by clonidine was associated with an increase of mean RR
intervals (slower heart rate) during quiet sleep periods and during a 70-s period
before the onset of rhythmic masticatory muscle activity episodes. However, no
changes in cardiac activity variables were observed for clonazepam. In young
adults with primary sleep bruxism, clonidine was significantly more effective in
suppressing sleep bruxism than clonazepam. The acute effects of clonidine on
rhythmic masticatory muscle activity episodes may be mediated by suppression of
autonomic nervous system activity and non-rapid eye movement-rapid eye movement
sleep processes.
PMID- 27485390
TI - Resident and family member perceptions of cultural diversity in aged care homes.
AB - Similar to many developed nations, older people living in residential aged care
homes in Australia and the staff who care for them have become increasingly
multicultural. This cultural diversity adds challenges for residents in adapting
to the care home. This study explores: (i) residents' and family members'
perceptions about staff and cultural diversity, and (ii) culturally and
linguistically diverse residents' and family members' experiences. An
interpretive study design employing a thematic analysis was applied. Twenty-three
residents and seven family members participated in interviews. Four themes were
identified from interpreting residents and family members' perceptions of the
impact of cultural diversity on their adaptation to aged care homes: (i)
perceiving diversity as an attraction; (ii) adapting to cross-cultural
communication; (iii) adjusting to diet in the residential care home; and (iv)
anticipating individualized psychosocial interactions. The findings have
implications for identifying strategies to support staff from all cultural
backgrounds in order to create a caring environment that facilitates positive
relationships with residents and supports residents to adjust to the care home.
PMID- 27485391
TI - Bacterial IgA protease-mediated degradation of agIgA1 and agIgA1 immune complexes
as a potential therapy for IgA Nephropathy.
AB - Mesangial deposition of aberrantly glycosylated IgA1 (agIgA1) and its immune
complexes is a key pathogenic mechanism of IgA nephropathy (IgAN). However,
treatment of IgAN remains ineffective. We report here that bacteria-derived IgA
proteases are capable of degrading these pathogenic agIgA1 and derived immune
complexes in vitro and in vivo. By screening 14 different bacterial strains (6
species), we found that 4 bacterial IgA proteases from H. influenzae, N.
gonorrhoeae and N. meningitidis exhibited high cleaving activities on serum
agIgA1 and artificial galactose-depleted IgA1 in vitro and the deposited agIgA1
containing immune complexes in the mesangium of renal biopsy from IgAN patients
and in a passive mouse model of IgAN in vitro. In the modified mouse model of
passive IgAN with abundant in situ mesangial deposition of the agIgA-IgG immune
complexes, a single intravenous delivery of IgA protease from H. influenzae was
able to effectively degrade the deposited agIgA-IgG immune complexes within the
glomerulus, demonstrating a therapeutic potential for IgAN. In conclusion, the
bacteria-derived IgA proteases are biologically active enzymes capable of
cleaving the circulating agIgA and the deposited agIgA-IgG immune complexes
within the kidney of IgAN. Thus, the use of such IgA proteases may represent a
novel therapy for IgAN.
PMID- 27485393
TI - Montelukast, current indications and prospective future applications.
AB - INTRODUCTION: Montelukast is recommended for the treatment of asthma, exercise
induced bronchospasm and allergic rhinitis. Several trials demonstrated potential
therapeutic effects in other respiratory conditions, and different animal-model
based studies explored potential pharmacological actions in non-respiratory
conditions. AREAS COVERED: Clinical investigations on the pharmacotherapeutic
effects of montelukast, in addition to in-vivo studies on animal models of non
respiratory diseases. The data discussed in this review were mainly obtained from
clinical randomized trials, real-life studies, and studies based on animal models
as approve of concept. As a condition, all of the discussed articles were
published in journals cited by Pubmed. Expert commentary: The current clinical
data are in favor of montelukast use in the management of chronic asthma as an
add-on or alternative therapy to the inhaled corticosteroids. Further clinical
trials are required to confirm the effectiveness and feasibility of montelukast
for the treatment of conditions other than the current clinical indications.
PMID- 27485394
TI - Stability of LAPONITE(r)-stabilized high internal phase Pickering emulsions under
shear.
AB - Colloidal particles are often used to make Pickering emulsions that are reported
to be very stable. Commonly the stabilization is a combined effect of particle
adsorbing at the fluid interface and a particle network in the continuous phase;
the contribution of each to the overall stability is difficult to assess. We
investigate the role of LAPONITE(r) particles on high internal phase emulsion
stability by considering three different situations: emulsion stabilization by
surfactant only, by surfactant plus clay particles, and finally clay particles
only. To clarify the structure of the emulsion and the role of the clay
particles, we have succeeded in fluorescently labelling the clay particles by
adsorbing the dye onto the particle surfaces. This allows us to show directly
using confocal microscopy, that the clay particles are not only located at the
interface but also aggregate and form a gel in the continuous aqueous phase. We
show that the emulsions in the presence of surfactant (with or without clay) are
stable to coalescence and shear. Without surfactant (with only LAPONITE(r) as
stabilizer) the emulsions are stable to coalescence for several weeks, however
they destabilize rapidly under shear. Our results suggest that the formation of
the emulsions is mostly due to gel formation of the clay particles in the
continuous phase, rather than that the clay is an emulsifier. This gel formation
also accounts for the instability of the emulsions to shear that we observe
caused by shear thinning of the continuous gel and inability of the adsorbed
particles to rearrange effectively around the droplets due to their attractive
nature.
PMID- 27485395
TI - Separation and analysis of mono-glucosylated lipids in brain and skin by
hydrophilic interaction chromatography based on carbohydrate and lipid moiety.
AB - Mono-glycosylated sphingolipids and glycerophospholipids play important roles in
diverse biological processes and are linked to a variety of pathologies, such as
Parkinson disease. The precise identification of the carbohydrate head group of
these lipids is complicated by their isobaric nature and by substantial
differences in concentration in different biological samples. To overcome these
obstacles, we developed a zwitterionic (ZIC)-hydrophilic interaction
chromatography (HILIC) electrospray ionization tandem mass spectrometry method.
ZIC-HILIC preferentially retains inositol, followed by glucose- and galactose
featuring lipids. Comparison with unmodified silica gel HILIC stationary phase
revealed different retention specificity. To evaluate the precision of ZIC-HILIC,
we quantified glucosyl- (GlcCer) and galactosylceramides (GalCer) in seven
different regions of the mouse brain and discovered that GlcCer and GalCer
concentrations are inversely related. The highest GalCer (lowest GlcCer) content
was found in the medulla oblongata and hippocampus, whereas the highest GlcCer
(lowest GalCer) content was found in other regions. With a neutral loss scan, ZIC
HILIC resolved glucosylceramide species featuring non-hydroxylated fatty acid,
hydroxylated fatty acid, and trihydroxy sphingoid bases in mouse epidermis
samples. This demonstrates that our ZIC-HILIC-based approach is a valuable tool
for characterizing the structural diversity of mono-glucosylated lipids in
biological material and for quantifying these important lipids.
PMID- 27485392
TI - Toward development of epigenetic drugs for central nervous system disorders:
Modulating neuroplasticity via H3K4 methylation.
AB - The mammalian brain dynamically activates or silences gene programs in response
to environmental input and developmental cues. This neuroplasticity is controlled
by signaling pathways that modify the activity, localization, and/or expression
of transcriptional-regulatory enzymes in combination with alterations in
chromatin structure in the nucleus. Consistent with this key neurobiological
role, disruptions in the fine-tuning of epigenetic and transcriptional regulation
have emerged as a recurrent theme in studies of the genetics of
neurodevelopmental and neuropsychiatric disorders. Furthermore, environmental
factors have been implicated in the increased risk of heterogeneous,
multifactorial, neuropsychiatric disorders via epigenetic mechanisms. Aberrant
epigenetic regulation of gene expression thus provides an attractive unifying
model for understanding the complex risk architecture of mental illness. Here, we
review emerging genetic evidence implicating dysregulation of histone lysine
methylation in neuropsychiatric disease and outline advancements in small
molecule probes targeting this chromatin modification. The emerging field of
neuroepigenetic research is poised to provide insight into the biochemical basis
of genetic risk for diverse neuropsychiatric disorders and to develop the highly
selective chemical tools and imaging agents necessary to dissect dynamic
transcriptional-regulatory mechanisms in the nervous system. On the basis of
these findings, continued advances may lead to the validation of novel, disease
modifying therapeutic targets for a range of disorders with aberrant chromatin
mediated neuroplasticity.
PMID- 27485396
TI - Elimination of biofilm and microbial contamination reservoirs in hospital
washbasin U-bends by automated cleaning and disinfection with electrochemically
activated solutions.
AB - BACKGROUND: Washbasin U-bends are reservoirs of microbial contamination in
healthcare environments. U-Bends are constantly full of water and harbour
microbial biofilm. AIM: To develop an effective automated cleaning and
disinfection system for U-bends using two solutions generated by electrochemical
activation of brine including the disinfectant anolyte (predominantly
hypochlorous acid) and catholyte (predominantly sodium hydroxide) with detergent
properties. METHODS: Initially three washbasin U-bends were manually filled with
catholyte followed by anolyte for 5min each once weekly for five weeks. A
programmable system was then developed with one washbasin that automated this
process. This U-bend had three cycles of 5min catholyte followed by 5min anolyte
treatment per week for three months. Quantitative bacterial counts from treated
and control U-bends were determined on blood agar (CBA), R2A, PAS, and PA agars
following automated treatment and on CBA and R2A following manual treatment.
FINDINGS: The average bacterial density from untreated U-bends throughout the
study was >1*10(5) cfu/swab on all media with Pseudomonas aeruginosa accounting
for ~50% of counts. Manual U-bend electrochemically activated (ECA) solution
treatment reduced counts significantly (<100cfu/swab) (P<0.01 for CBA; P<0.005
for R2A). Similarly, counts from the automated ECA-treatment U-bend were
significantly reduced with average counts for 35 cycles on CBA, R2A, PAS, and PA
of 2.1+/-4.5 (P<0.0001), 13.1+/-30.1 (P<0.05), 0.7+/-2.8 (P<0.001), and 0
(P<0.05) cfu/swab, respectively. P. aeruginosa was eliminated from all treated U
bends. CONCLUSION: Automated ECA treatment of washbasin U-bends consistently
minimizes microbial contamination.
PMID- 27485397
TI - Expression of cyclooxygenases and trophic and growth factors in epiretinal
membranes at late stages of proliferative vitreoretinopathy.
PMID- 27485398
TI - Preparation and preclinical evaluation of a freeze-dried formulation of a novel
combined multivalent whole-cell/B-subunit oral vaccine against enterotoxigenic
Escherichia coli diarrhea.
AB - A promising liquid killed multivalent whole-cell plus enterotoxin B-subunit oral
vaccine against enterotoxigenic Escherichia coli (ETEC), the primary cause of
diarrhea among children in low-income countries and travelers to these areas, has
recently been developed and tested in preclinical and phase-I and phase-II
clinical studies. The vaccine contains killed E. coli bacteria over-expressing
the main ETEC colonization factors (CFs) CFA/I, CS3, C5 and C6, and a recombinant
enterotoxin B subunit protein (LCTBA) given together with a recently developed
enterotoxin-derived adjuvant, dmLT. A dry-powder vaccine formulation should be
advantageous especially for use in low-income countries. Here we describe a
method to produce a dry-powder formulation by freeze-drying of the vaccine using
inulin as stabilizer. Although not completely preventing aggregation of bacteria
during freeze-drying, the stabilizer provided both improved overall bacterial
morphology and almost complete recovery of the CF and B subunit antigens. Most
importantly, oral-intragastric immunization of mice with the freeze-dried vaccine
together with dmLT adjuvant elicited strong intestinal mucosal and serum antibody
responses against all vaccine antigens, which were comparable to those achieved
with the liquid vaccine. Our results indicate the feasibility to use freeze
drying with inulin as stabilizer for preparing a dry-powder formulation of the
novel ETEC vaccine with retained oral-mucosal immunogenicity compared to the
liquid formulation.
PMID- 27485399
TI - Novel virtual lead identification in the discovery of hematopoietic cell kinase
(HCK) inhibitors: application of 3D QSAR and molecular dynamics simulation.
AB - High level of hematopoietic cell kinase (Hck) is associated with drug resistance
in chronic myeloid leukemia. Additionally, Hck activity has also been connected
with the pathogenesis of HIV-1 and chronic obstructive pulmonary disease. In this
study, three-dimensional (3D) QSAR pharmacophore models were generated for Hck
based on experimentally known inhibitors. A best pharmacophore model, Hypo1, was
developed with high correlation coefficient (0.975), Low RMS deviation (0.60) and
large cost difference (49.31), containing three ring aromatic and one hydrophobic
aliphatic feature. It was further validated by the test set (r = 0.96) and
Fisher's randomization method (95%). Hypo 1 was used as a 3D query for screening
the chemical databases, and the hits were further screened by applying Lipinski's
rule of five and ADMET properties. Selected hit compounds were subjected to
molecular docking to identify binding conformations in the active site. Finally,
the appropriate binding modes of final hit compounds were revealed by molecular
dynamics (MD) simulations and free energy calculation studies. Hence, we propose
the final three hit compounds as virtual candidates for Hck inhibitors.
PMID- 27485400
TI - Senescence: Adaptation to DNA repair targeting drugs?
PMID- 27485401
TI - Interactive effects of attachment and FKBP5 genotype on school-aged children's
emotion regulation and depressive symptoms.
AB - Attachment insecurity is influenced by both environmental and genetic factors,
but few studies have examined the effects of gene-environment interactions. In
the context of environmental stress, a functional variant in the glucocorticoid
receptor co-chaperone FKBP5 gene has been repeatedly shown to increase risk for
psychiatric illness, including depression. We expand on prior work by exploring
cross-sectional attachment by gene effects on both attachment insecurity and
downstream physiological and behavioral measures in a diverse community sample of
school-aged children (N=99, 49% girls, Mage=10.29years, 66.6% non-White) and
their mothers. Specifically, we examined moderating effects of FKBP5 rs3800373
genotype on the links between parenting insensitivity (overcontrol) and child
attachment. Further, we assessed whether FKBP5 moderates the links between
maternal and child attachment and children's emotion regulation self-report,
respiratory sinus arrhythmia (RSA) in response to a standardized laboratory
stressor, and depressive symptoms. Higher levels of overcontrol predicted lower
child attachment security only in FKBP5 minor allele carriers. Among children
with two minor alleles (CC), attachment security was negatively associated with
emotion suppression, rumination, depressive symptoms, and RSA reactivity;
similarly, for these children, maternal attachment anxiety was positively
associated with depressive symptoms. The findings can be conceptualized in a
differential susceptibility framework, where the FKBP5 minor allele confers
either risk or resilience, depending on the parenting environment.
PMID- 27485402
TI - The lateral septum and anterior hypothalamus act in tandem to regulate burying in
the shock-probe test but not open-arm avoidance in the elevated plus-maze.
AB - Both the lateral septum (LS) and anterior hypothalamus (AHA) regulate behavioural
defense. We tested whether those two interconnected structures act in serial in
that regard. Infusions of the GABAA agonist muscimol into one side of the LS and
the contralateral (but not ipsilateral) AHA suppressed rats' burying in the shock
probe test whereas none of our muscimol infusion approaches altered their open
arm avoidance in the elevated plus-maze. These results suggest that the LS-AHA
circuit serves a specialized role in defensive responses towards discrete,
localizable threat stimuli but not towards potential threats.
PMID- 27485403
TI - Alternating Current Influences Anaerobic Electroactive Biofilm Activity.
AB - Alternating current (AC) is known to inactivate microbial growth in suspension,
but how AC influences anaerobic biofilm activities has not been systematically
investigated. Using a Geobacter dominated anaerobic biofilm growing on the
electrodes of microbial electrochemical reactors, we found that high frequency AC
ranging from 1 MHz to 1 kHz (amplitude of 5 V, 30 min) showed only temporary
inhibition to the biofilm activity. However, lower frequency (100 Hz, 1.2 or 5 V)
treatment led to 47 +/- 19% permanent decrease in limiting current on the same
biofilm, which is attributed to the action of electrohydrodynamic force that
caused biofilm damage and loss of intercellular electron transfer network.
Confocal microscopy images show such inactivation mainly occurred at the
interface between the biofilm and the electrode. Reducing the frequency further
to 1 Hz led to water electrolysis, which generated gas bubbles that flushed all
attached cells out of the electrode. These findings provide new references on
understanding and regulating biofilm growth, which has broader implications in
biofouling control, anaerobic waste treatment, energy and product recovery, and
general understanding of microbial ecology and physiology.
PMID- 27485404
TI - Carbidopa-assisted 18F-fluorodihydroxyphenylalanine PET/CT for the localization
and staging of non-functioning neuroendocrine pancreatic tumors.
AB - OBJECTIVE: CD premedication was found to increase the value of 18F
fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT imaging in the detection of adult
insulinoma. The aim of this study was to evaluate the performance of CD-assisted
18F-FDOPA PET/CT in the diagnosis and staging of non-functioning pNETs. METHODS:
Twenty consecutive patients with low-grade pNETs who underwent CD-assisted 18F
FDOPA PET/CT imaging and 111In-somatostatin receptor scintigraphy (SRS) were
evaluated. Histology was considered as the gold standard. In case where no
surgical resection was performed, the diagnosis of pNET was made by the
confrontation of the different available imaging modalities. RESULTS: CD-assisted
18F-FDOPA PET/CT was positive in 18/20 cases (90 %), whereas SRS was positive in
13/19 cases (68 %). When considered the 19 patients underwent both nuclear
medicine examinations, 18F-FDOPA PET/CT was significantly more sensitive then SRS
for primary tumor detection (p = 0.049). False-negative results of both 18F-FDOPA
PET/CT and SRS were observed in 2 cystic pNETs. SRS failed to detect one
additional cystic tumor and 3 pNETs of 10, 12 and 17 mm, respectively. 18F-FDOPA
PET/CT correctly identified all patients with lymphatic, visceral and bone
metastases. SRS failed to detect lymphatic spread and was falsely negative in one
patient with splenic metastasis. CONCLUSIONS: Contrary to widely held
assumptions, our study further expands the application of CD-assisted 18F-FDOPA
PET/CT for non-functioning pNETs when 68Ga-radiolabeled somatostatin analogs are
not available.
PMID- 27485405
TI - Effects of left ventricular size on the accuracy of diastolic parameters derived
from myocardial perfusion SPECT: comparison with tissue Doppler echocardiography.
AB - BACKGROUND: Impaired left ventricular (LV) diastolic function is a sensitive and
early sign of myocardial ischemia. We evaluated the effects of LV size on the
accuracy of diastolic parameters derived from SPECT. METHODS: The study
population consisted of 151 patients with known or suspected coronary artery
disease who underwent both SPECT and transthoracic echocardiography. Peak filling
rate (PFR), one-third mean filling rate (1/3 MFR) and the ratio of time to PFR to
the RR interval (TPFR/RR) were calculated by quantitative gated SPECT. Peak early
mitral annular velocity (e') was used as the reference standard of LV diastolic
function. RESULTS: There were 43 patients with end-systolic volume (ESV) of <=10
ml, 43 patients with ESV of 11-20 ml and 65 patients with ESV of >20 ml. There
were significant differences in PFR (p < 0.001), 1/3 MFR (p < 0.001) or TPFR/RR
(p = 0.01) among the 3 groups. These diastolic parameters were increased with
decreased LV size. In overall patients, PFR (r = 0.24, p = 0.003) and 1/3 MFR (r
= 0.31, p < 0.001) were positively, and TPFR/RR (r = -0.23, p = 0.004) was
inversely correlated with e'. Multivariate linear regression analyses showed that
male gender (beta = -0.14, p = 0.07; beta = -0.16, p = 0.04), ESV (beta = -0.63,
p < 0.001; beta = -0.45, p < 0.001) and e' (beta = 0.36, p < 0.001; beta = 0.40,
p < 0.001) were significant factors associated with PFR or 1/3 MFR. Multivariate
linear regression analysis also showed that ESV (beta = -0.17, p = 0.03) and e'
(beta = -0.21, p = 0.01) were significant factors associated with TPFR/RR.
CONCLUSIONS: Our data suggest that PFR, 1/3 MFR and TPFR/RR derived from SPECT
are correlated with e' as the reference standard of LV diastolic function, but
are overestimated in small-sized heart. LV size should be taken into
consideration when interpreting these diastolic parameters.
PMID- 27485406
TI - Cerebral hyperperfusion syndrome resulting in subarachnoid hemorrhage after
carotid artery stenting.
AB - A 64-year-old, right-handed man underwent endovascular treatment for internal
carotid artery stenosis after experiencing a left-hemispheric transient ischemic
attack. 15O-gas and H 215 O positron emission tomography revealed slightly
reduced cerebral blood flow (CBF), elevated cerebral blood volume, and severely
reduced cerebral vasoreactivity in the ipsilateral hemisphere as determined by an
acetazolamide challenge test. The patient underwent left carotid artery stenting
(CAS) via a prefemoral approach under local anesthesia without any complications.
Follow-up examinations performed 20 h postoperatively showed subarachnoid
hemorrhage (SAH) and cerebral hyperperfusion syndrome (CHS) in the left frontal
lobe. Although it is a relatively rare phenomenon, SAH resulting from CHS was
determined to be specifically caused by CAS. In this case, the causes of SAH may
have been related to multiple factors including increased regional CBF, loss of
cerebrovascular autoregulation, contrast agent-mediated disruption of major
cerebral vessels, and strong antiplatelet therapy.
PMID- 27485408
TI - A new early-onset neuromuscular disorder associated with kyphoscoliosis peptidase
(KY) deficiency.
AB - We describe a new early-onset neuromuscular disorder due to a homozygous loss-of
function variant in the kyphoscoliosis peptidase gene (KY). A 7.5-year-old girl
with walking difficulties from 2 years of age presented with generalized muscle
weakness; mild contractures in the shoulders, hips and feet; cavus feet; and
lordosis but no scoliosis. She had previously been operated with Achilles tendon
elongation. Whole-body MRI showed atrophy and fatty infiltration in the calf
muscles. Biopsy of the vastus lateralis muscle showed variability in fiber size,
with some internalized nuclei and numerous very small fibers with variable
expression of developmental myosin heavy chain isoforms. Some small fibers showed
abnormal sarcomeres with thickened Z-discs and small nemaline rods. Whole-exome
sequencing revealed a homozygous one-base deletion (c.1071delG,
p.(Thr358Leufs*3)) in KY, predicted to result in a truncated protein. Analysis of
an RNA panel showed that KY is predominantly expressed in skeletal muscle in
humans. A recessive variant in the murine ortholog Ky was previously described in
a spontaneously generated mouse mutant with kyphoscoliosis, which developed
postnatally and was caused by dystrophy of postural muscles. The abnormal
distribution of Xin and Ky-binding partner filamin C in the muscle fibers of our
patient was highly similar to their altered localization in ky/ky mouse muscle
fibers. We describe the first human case of disease associated with KY
inactivation. As in the mouse model, the affected child showed a neuromuscular
disorder - but in contrast, no kyphoscoliosis.
PMID- 27485407
TI - Cadmium, lead and mercury concentrations in pathologically altered human kidneys.
AB - Heavy metals, including cadmium (Cd), lead (Pb) and mercury (Hg) act as
nephrotoxic agents, particularly in the renal cortex. The aim of the study was to
determine the concentrations of Cd, Pb and Hg in kidneys removed from patients
due to lesions of various etiologies and from patients after the rejection of
transplanted kidneys. Additionally, we determined the influence of selected
biological and environmental factors on the concentrations of toxic metals. The
study material consisted of kidneys with tumor lesions (n = 27), without tumors
(n = 7) and its extracted grafts (n = 10) obtained from patients belongs to the
north-western areas of Poland. The determined metal concentrations in the renal
cortex and medulla may be arranged in the following descending order: Cd > Pb >
Hg. The highest concentrations of Cd and Hg were found in the cortex, while the
maximum content Pb was observed in the medulla. Significant correlations were
found in the concentrations of the same metals between cortex and medulla and
between Pb and Hg in the renal medulla. Pb content was higher in the renal
medulla of men than in the cortex of the elderly (above 60 years of age). The
highest concentrations of Pb and Hg were found in the cortex and medulla, of the
kidneys had not neoplastic changes, and lower content of these metals were found
in the extracted kidney grafts. In summary, renal grafts accumulate less heavy
metals than cancerous kidneys, what could have been caused by immunosuppressors
taken by the graft recipients. Moreover, sex, age and smoking are key factors
responsible for xenobiotics concentrations.
PMID- 27485409
TI - Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a
MICOS complex subunit.
AB - The mitochondrial inner membrane possesses distinct subdomains including cristae,
which are lamellar structures invaginated into the mitochondrial matrix and
contain the respiratory complexes. Generation of inner membrane domains requires
the complex interplay between the respiratory complexes, mitochondrial lipids and
the recently identified mitochondrial contact site and cristae organizing system
(MICOS) complex. Proper organization of the mitochondrial inner membrane has
recently been shown to be important for respiratory function in yeast. Here we
aimed at a molecular diagnosis in a brother and sister from a consanguineous
family who presented with a neurodegenerative disorder accompanied by
hyperlactatemia, 3-methylglutaconic aciduria, disturbed hepatocellular function
with abnormal cristae morphology in liver and cerebellar and vermis atrophy,
which suggest mitochondrial dysfunction. Using homozygosity mapping and exome
sequencing the patients were found to be homozygous for the p.(Gly15Glufs*75)
variant in the QIL1/MIC13 (C19orf70) gene. QIL1/MIC13 is a constituent of MICOS,
a six subunit complex that helps to form and/or stabilize cristae junctions and
determine the placement, distribution and number of cristae within mitochondria.
In patient fibroblasts both MICOS subunits QIL1/MIC13 and MIC10 were absent
whereas MIC60 was present in a comparable abundance to that of the control. We
conclude that QIL1/MIC13 deficiency in human, is associated with disassembly of
the MICOS complex, with the associated aberration of cristae morphology and
mitochondrial respiratory dysfunction. 3-Methylglutaconic aciduria is associated
with variants in genes encoding mitochondrial inner membrane organizing
determinants, including TAZ, DNAJC19, SERAC1 and QIL1/MIC13.
PMID- 27485410
TI - Clinical Utility Gene Card for: Familial partial lipodystrophy.
PMID- 27485411
TI - Copy number variation of the REXO1L1 gene cluster; euchromatic deletion variant
or susceptibility factor?
PMID- 27485412
TI - Lack of gene-language correlation due to reciprocal female but directional male
admixture in Austronesians and non-Austronesians of East Timor.
AB - Nusa Tenggara, including East Timor, located at the crossroad between Island
Southeast Asia, Near Oceania, and Australia, are characterized by a complex
cultural structure harbouring speakers from two different major linguistic groups
of different geographic origins (Austronesian (AN) and non-Austronesian (NAN)).
This provides suitable possibilities to study gene-language relationship;
however, previous studies from other parts of Nusa Tenggara reported conflicting
evidence about gene-language correlation in this region. Aiming to investigate
gene-language relationships including sex-mediated aspects in East Timor, we
analysed the paternally inherited non-recombining part of the Y chromosome (NRY)
and the maternally inherited mitochondrial (mt) DNA in a representative
collection of AN- and NAN-speaking groups. Y-SNP (single-nucleotide polymorphism)
data were newly generated for 273 samples and combined with previously
established Y-STR (short tandem repeat) data of the same samples, and with
previously established mtDNA data of 290 different samples with, however, very
similar representation of geographic and linguistic coverage of the country. We
found NRY and mtDNA haplogroups of previously described putative East/Southeast
Asian (E/SEA) and Near Oceanian (NO) origins in both AN and NAN speakers of East
Timor, albeit in different proportions, suggesting reciprocal genetic admixture
between both linguistic groups for females, but directional admixture for males.
Our data underline the dual genetic origin of East Timorese in E/SEA and NO, and
highlight that substantial genetic admixture between the two major linguistic
groups had occurred, more so via women than men. Our study therefore provides
another example where languages and genes do not conform due to sex-biased
genetic admixture across major linguistic groups.
PMID- 27485413
TI - Searching Missing Proteins Based on the Optimization of Membrane Protein
Enrichment and Digestion Process.
AB - A membrane protein enrichment method composed of ultracentrifugation and
detergent-based extraction was first developed based on MCF7 cell line. Then, in
solution digestion with detergents and eFASP (enhanced filter-aided sample
preparation) with detergents were compared with the time-consuming in-gel
digestion method. Among the in-solution digestion strategies, the eFASP combined
with RapiGest identified 1125 membrane proteins. Similarly, the eFASP combined
with sodium deoxycholate identified 1069 membrane proteins; however, the in-gel
digestion characterized 1091 membrane proteins. Totally, with the five digestion
methods, 1390 membrane proteins were identified with >=1 unique peptides, among
which 1345 membrane proteins contain unique peptides >=2. This is the biggest
membrane protein data set for MCF7 cell line and even breast cancer tissue
samples. Interestingly, we identified 13 unique peptides belonging to 8 missing
proteins (MPs). Finally, eight unique peptides were validated by synthesized
peptides. Two proteins were confirmed as MPs, and another two proteins were
candidate detections.
PMID- 27485414
TI - An analysis of the relationship between metastases and cachexia in lung cancer
patients.
AB - Weight loss and hematogenous metastases are poor prognosis factors in lung cancer
patients that can but do not necessarily co-occur. We retrospectively
investigated the clinical association between cachexia, tumor characteristics
(such as metastatic burden and mutational status), and treatment in lung cancer
patients. The medical records of 394 lung cancer patients from two institutions
(Columbia University, USA and Tohoku University, Japan) were reviewed.
Information collected included the presence of cachexia, histologic subtype,
tumor stage, number of metastases, mutation status, treatment, and survival.
Descriptive statistics were performed. Only stage IV patients exhibited >5%
weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001).
Patients with metastases developed cachexia more often than patients without
metastases independent of treatment (6.0% and 7.1% weight loss in patients with
metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001]
and after [P < 0.0001] treatment, respectively). The change in number of
metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%,
13.4%, and 13.4%, for an increase of 0, 1, 2, and >=3 metastatic sites, from
initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse
survival than patients without cachexia (hazard ratio, 2.94; 95% confidence
interval, 2.08-4.16; P < 0.0001). Tumors with mutated KRAS were associated with
an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS
vs. 6.0% in patients with wild-type KRAS; P = 0.0011). Our findings suggest that
the capabilities of lung cancer to metastasize and cause cachexia might be linked
intrinsically and are independent of treatments administered. KRAS-mutated tumors
were more commonly associated with cachexia.
PMID- 27485415
TI - Nitidine chloride inhibits proliferation, induces apoptosis via the Akt pathway
and exhibits a synergistic effect with doxorubicin in ovarian cancer cells.
AB - Nitidine chloride (NC) exhibits anti-tumor properties in various types of tumor.
However, to the best of our knowledge there is no previous evidence of NC
involvement in the apoptosis or proliferation of ovarian cancer cells and the
underlying molecular mechanisms. The present study aimed to investigate the
influence of NC on the viability and apoptosis of ovarian cancer cells and the
synergistic effect NC and doxorubicin (DOX) may have on ovarian cancer cells. The
viability and proliferation of ovarian cancer cells were examined using a methyl
thiazolyl tetrazolium assay and 3H-thymidine incorporation assay. The apoptotic
rate of ovarian cancer cells was detected by flow cytometry. The expression of
apoptosis-associated proteins and Akt serine/threonine kinase 1 (Akt) were
determined by western blot analysis following NC treatment. The inhibitory effect
of NC on the proliferation of ovarian cancer cells was demonstrated in a time and
dose-dependent manner. The pro-apoptotic effect of NC on ovarian cancer cells was
also observed. It was determined that NC significantly downregulated the protein
expression levels of B-cell CLL/lymphoma 2 (Bcl-2) and upregulated the expression
of Bcl-2-associated X protein, p53, caspase-3 and -9. NC suppressed Akt
phosphorylation. Additionally, the present study demonstrated that the effect of
NC on the proliferation and apoptosis of ovarian cancer cells was Akt-dependent
by using the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt signaling pathway
inhibitor, LY294002. NC exhibited a synergistic inhibitory effect on the
viability of ovarian cancer cells when combined with DOX. The current study
demonstrated that NC inhibited the proliferation and induced the apoptosis of
ovarian cancer cells via the Akt signaling pathway and highlighted its potential
clinical application for the treatment of ovarian cancer.
PMID- 27485417
TI - Editorial: Chemoinformatics in Japan.
PMID- 27485416
TI - Migration of a shotgun pellet into the L7-S1 intervertebral foramen of a hunting
dog.
PMID- 27485418
TI - Benchmarking a Wide Range of Chemical Descriptors for Drug-Target Interaction
Prediction Using a Chemogenomic Approach.
AB - The identification of drug-target interactions, or interactions between drug
candidate compounds and target candidate proteins, is a crucial process in
genomic drug discovery. In silico chemogenomic methods are recently recognized as
a promising approach for genome-wide scale prediction of drug-target
interactions, but the prediction performance depends heavily on the descriptors
and similarity measures of drugs and proteins. In this paper, we investigated the
performance of various descriptors and similarity measures of drugs and proteins
for the drug-target interaction prediction using a chemogenomic approach. We
compared the prediction accuracy of 18 chemical descriptors of drugs (e.g., ECFP,
FCFP,E-state, CDK, Klekota?Roth, MACCS, PubChem, Dragon, KCF-S, and graph
kernels) and 4 descriptors of proteins (e.g., amino acid composition, domain
profile, local sequence similarity, and string kernel) on about one hundred
thousand drug-target interactions. We examined the combinatorial effects of drug
descriptors and protein descriptors using the same benchmark data under several
experimental conditions. Large-scale experiments showed that our proposed KCF-S
descriptor worked the best in terms of prediction accuracy. The comparative
results are expected to be useful for selecting chemical descriptors in various
pharmaceutical applications.
PMID- 27485419
TI - Constructing a Foundational Platform Driven by Japan's K Supercomputer for Next
Generation Drug Design.
AB - The cost of pharmaceutical R&D has risen enormously, both worldwide and in Japan.
However, Japan faces a particularly difficult situation in that its population is
aging rapidly, and the cost of pharmaceutical R&D affects not only the industry
but the entire medical system as well. To attempt to reduce costs, the newly
launched K supercomputer is available for big data drug discovery and structural
simulation-based drug discovery. We have implemented both primary (direct) and
secondary (infrastructure, data processing) methods for the two types of drug
discovery, custom tailored to maximally use the 88 128 compute nodes/CPUs of K,
and evaluated the implementations. We present two types of results. In the first,
we executed the virtual screening of nearly 19 billion compound-protein
interactions, and calculated the accuracy of predictions against publicly
available experimental data. In the second investigation, we implemented a very
computationally intensive binding free energy algorithm, and found that
comparison of our binding free energies was considerably accurate when validated
against another type of publicly available experimental data. The common feature
of both result types is the scale at which computations were executed. The
frameworks presented in this article provide prospectives and applications that,
while tuned to the computing resources available in Japan, are equally applicable
to any equivalent large-scale infrastructure provided elsewhere.
PMID- 27485421
TI - Data Mining of Chemogenomics Data Using Bi-Modal PLS Methods and Chemical
Interpretation for Molecular Design.
AB - Chemogenomics is a new strategy in drug discovery for interrogating all molecules
capable of interacting with all biological targets. Because of the almost
infinite number of drug-like organic molecules, bench-based experimental
chemogenomics methods are not generally feasible. Several in silico chemogenomics
models have therefore been developed for high-throughput screening of large
numbers of drug candidate compounds and target proteins. In previous studies, we
described two novel bi-modal PLS approaches. These methods provide a significant
advantage in that they enable direct connections to be made between biological
activities and ligand and protein descriptors. In this special issue, we review
these two PLS-based approaches using two different chemogenomics datasets for
illustration. We then compare the predictive and interpretive performance of the
two methods using the same congeneric data set.
PMID- 27485420
TI - In Silico Investigation of a HIV-1 Vpr Inhibitor Binding Site: Potential for
Virtual Screening and anti-HIV Drug Design.
AB - Present HIV antiviral therapy only targets structural proteins of HIV, but
evidence shows that the targeting of accessory proteins will expand our options
in combating HIV. HIV-1 Vpr, a multifunctional accessory protein involved in
viral infection, replication and pathogenesis, is a potential target. Previously,
we have shown that phenyl coumarin compounds can inhibit the growth arrest
activity of Vpr in host cells and predicted that the inhibitors' binding site is
a hydrophobic pocket on Vpr. To investigate our prediction of the inhibitors'
binding site, we docked the coumarin inhibitors into the predicted hydrophobic
binding pocket on a built model of Vpr and observed a linear trend between their
calculated binding energies and prior experimentally determined potencies.
Subsequently, to analyze the inhibitor-protein binding interactions in detail, we
built homology models of Vpr mutants and performed docking studies on these
models too. The results revealed that structural changes on the binding pocket
that were caused by the mutations affected inhibitor binding. Overall, this study
showed that the binding energies of the docked molecules are good indicators of
the activity of the inhibitors. Thus, the model can be used in virtual screening
to identify other Vpr inhibitors and for designing more potent inhibitors.
PMID- 27485422
TI - Multivariate Analysis of Side Effects of Drug Molecules Based on Knowledge of
Protein Bindings and Protein?Protein Interactions.
AB - Here, we examined the relationships between 969 side effects associated with 658
drugs and their 1368 human protein targets using our hybrid approaches. Firstly,
L-shaped PLS (LPLS) was used to construct a multivariate model of side effects
and protein bindings of drug molecules. LPLS is an extension of standard PLS
regression, where, in addition to the response matrix Y and the regressor matrix
X, an extra data matrix Z is constructed that summarizes the background
information of X. X and Y are matrices comprising drugs-target proteins, and
drugs-side effects, respectively. The Z matrix is the protein?protein interaction
data. From the loading plot of Y, we could identify two remarkable side effects
(urinary incontinence and increased salivation) From the corresponding loading
plot of X, the responsible protein targets causing each side effect could be
estimated (sodium channels and gamma-aminobutyric acid (GABA) receptors). The
loading plot of the Z matrix indicated that the GABA receptors interact with each
other and they heavily influence the side effect of increased salivation.
Secondly, Bayesian classifier methods were separately applied to the cases of the
two side effects. That is, the Bayesian classifier method was used to classify
drug molecules as binding or not binding to the responsible protein targets
associated with each side effect. Using atom-coloring techniques, it was possible
to estimate which fragments on the drug molecule might cause the specific side
effects. This information is valuable for drug design to avoid specific side
effects.
PMID- 27485423
TI - Ring-System-Based Exhaustive Structure Generation for Inverse-QSPR/QSAR.
AB - Inverse-QSPR/QSAR aims to solve the inverse problem of chemical structure
generation based on QSPR/QSAR models, once the properties or activities are
specified. To efficiently solve this problem, an exhaustive ring-system-based
structure generation methodology was developed. The concept of the applicability
domain (AD) is automatically acknowledged within the proposed strategy. The local
AD is considered by introducing the probability distribution of a given data set,
and the universal AD is considered using ring-system-based fragments in the
training data set. Structures with desired properties or activities are
enumerated by assembling fragments, including atomic elements, in a tree-like
way. The usefulness of the proposed method is demonstrated through a case study
of ligand design for the human alpha 2A adrenergic receptor (ADR2A_HUMAN). We
succeeded in generating structures focusing only on a pre-defined region in
chemical space, resulting in structures whose desired activity has a high
likelihood being efficiently generated. In addition, the limitations of our
proposed method and future challenges are discussed.
PMID- 27485424
TI - Development of a New De Novo Design Algorithm for Exploring Chemical Space.
AB - In the first stage of development of new drugs, various lead compounds with high
activity are required. To design such compounds, we focus on chemical space
defined by structural descriptors. New compounds close to areas where highly
active compounds exist will show the same degree of activity. We have developed a
new de novo design system to search a target area in chemical space. First,
highly active compounds are manually selected as initial seeds. Then, the seeds
are entered into our system, and structures slightly different from the seeds are
generated and pooled. Next, seeds are selected from the new structure pool based
on the distance from target coordinates on the map. To test the algorithm, we
used two datasets of ligand binding affinity and showed that the proposed
generator could produce diverse virtual compounds that had high activity in
docking simulations.
PMID- 27485425
TI - Clustering of 3D-Structure Similarity Based Network of Secondary Metabolites
Reveals Their Relationships with Biological Activities.
AB - Developing database systems connecting diverse species based on omics is the most
important theme in big data biology. To attain this purpose, we have developed
KNApSAcK Family Databases, which are utilized in a number of researches in
metabolomics. In the present study, we have developed a network-based approach to
analyze relationships between 3D structure and biological activity of metabolites
consisting of four steps as follows: construction of a network of metabolites
based on structural similarity (Step 1), classification of metabolites into
structure groups (Step 2), assessment of statistically significant relations
between structure groups and biological activities (Step 3), and 2-dimensional
clustering of the constructed data matrix based on statistically significant
relations between structure groups and biological activities (Step 4). Applying
this method to a data set consisting of 2072 secondary metabolites and 140
biological activities reported in KNApSAcK Metabolite Activity DB, we obtained
983 statistically significant structure group-biological activity pairs. As a
whole, we systematically analyzed the relationship between 3D-chemical structures
of metabolites and biological activities.
PMID- 27485426
TI - Connecting Classical QSAR and LERE Analyses Using Modern Molecular Calculations,
LERE-QSAR (VI): Hydrolysis of Substituted Hippuric Acid Phenyl Esters by Trypsin.
AB - The reaction mechanism of trypsin was studied by applying DFT and ab initio
molecular orbital (MO) calculations to complexes of trypsin with a congeneric
series of eight para-substituted hippuric acid phenyl esters, for which a
previous quantitative structure?activity relationship (QSAR) study revealed nice
linearity of Hammett substitution constant sigma(-) with logarithmic values of
the Michaelis?Menten and catalytic rate constants. Based on the LERE procedure,
we performed QSAR analyses on each elementary reaction step during the acylation
process. The present calculations showed that the rate-determining step during
the acylation process is the transition state (TS) between the enzyme?substrate
complex (ES) and tetrahedral intermediate (TET), and that the proton transfer
occurs from Ser195 to His57, not between His57 and Asp102. The LERE-QSAR analysis
statistically suggested that the variation of overall free-energy changes leading
to formation of TS is governed mostly by that of activation energies required to
form TS from ES. In spite of a very limited number of congeneric ligands in the
current work, it is critically essential to clarify and verify physicochemical
meanings of a typical QSAR/Chemoinformatics parameter, Hammett sigma(-) based on
quantum chemical calculations on the protein?ligand kinetics; how Hammett sigma(
) behaves in terms of protein?ligand interaction energies.
PMID- 27485429
TI - Dose-response meta-analysis of differences in means.
AB - BACKGROUND: Meta-analytical methods are frequently used to combine dose-response
findings expressed in terms of relative risks. However, no methodology has been
established when results are summarized in terms of differences in means of
quantitative outcomes. METHODS: We proposed a two-stage approach. A flexible dose
response model is estimated within each study (first stage) taking into account
the covariance of the data points (mean differences, standardized mean
differences). Parameters describing the study-specific curves are then combined
using a multivariate random-effects model (second stage) to address heterogeneity
across studies. RESULTS: The method is fairly general and can accommodate a
variety of parametric functions. Compared to traditional non-linear models (e.g.
E max, logistic), spline models do not assume any pre-specified dose-response
curve. Spline models allow inclusion of studies with a small number of dose
levels, and almost any shape, even non monotonic ones, can be estimated using
only two parameters. We illustrated the method using dose-response data arising
from five clinical trials on an antipsychotic drug, aripiprazole, and improvement
in symptoms in shizoaffective patients. Using the Positive and Negative Syndrome
Scale (PANSS), pooled results indicated a non-linear association with the maximum
change in mean PANSS score equal to 10.40 (95 % confidence interval 7.48, 13.30)
observed for 19.32 mg/day of aripiprazole. No substantial change in PANSS score
was observed above this value. An estimated dose of 10.43 mg/day was found to
produce 80 % of the maximum predicted response. CONCLUSION: The described
approach should be adopted to combine correlated differences in means of
quantitative outcomes arising from multiple studies. Sensitivity analysis can be
a useful tool to assess the robustness of the overall dose-response curve to
different modelling strategies. A user-friendly R package has been developed to
facilitate applications by practitioners.
PMID- 27485428
TI - Comparing Different Sequential Mediational Interpretations of Beck's Cognitive
Model of Depression in Adolescents.
AB - Depression is a developmental phenomenon with significantly increasing rates
during adolescence. As Beck's cognitive model of depression has been commonly
accepted to explain the development and maintenance of depression, it is crucial
to understand how and when cognitive vulnerabilities predicted in this model
begin to interact. Three sequential interpretations of this model were compared.
The causal mediational interpretation identifies dysfunctional attitudes as most
distal to depressive symptoms, followed by cognitive errors, cognitive triad, and
negative automatic thoughts, with each construct successively more proximal to
depressive symptoms. In the symptom model the causal chain is reversed, with
depressive symptoms as the most distal construct, followed by negative automatic
thoughts, the cognitive triad, cognitive errors, and then dysfunctional
attitudes. The bidirectional model merges both interpretations in which the
activation of cognitive constructs causes the development of depressive symptoms
which in turn trigger and reinforce already existing dysfunctional attitudes.
Further, while Beck's model of depression proposes full mediation, empirical
studies identified repeatedly partial mediations. Thus, the causal meditational,
the symptoms, and the bidirectional model were each tested as full and partial
mediation models. Finally, sex differences in the associations between variables
were studied. In the 3-wave longitudinal study, 518 high school students (62.7 %
female, average age: 15.09 years) completed questionnaires measuring all
mentioned elements of Beck's model. The bidirectional model with partial
mediation fits the data best. Cognitive errors emerged as the main mediator in
the bidirectional model with partial mediation and significant sex differences in
the strengths of associations were identified. The findings demonstrate the
relevance of adolescence as developmental period during which the examined
associations develop into the network they form in adulthood. Further,
psychological interventions focusing on cognitive errors promise to be most
effective.
PMID- 27485430
TI - Variant detection and runs of homozygosity in next generation sequencing data
elucidate the genetic background of Lundehund syndrome.
AB - BACKGROUND: The Lundehund is a highly specialized breed characterized by a unique
flexibility of the joints and polydactyly in all four limbs. The extremely small
population size and high inbreeding has promoted a high frequency of diseased
dogs affected by the Lundehund syndrome (LS), a severe gastro-enteropathic
disease. RESULTS: Comprehensive analysis of bead chip and whole-genome sequencing
data for LS in the Lundehund resulted in a genome-wide association signal on CFA
34 and LS-specific runs of homozygosity (ROH) in this region. Filtering analysis
for variants with predicted high or moderate effects revealed a missense mutation
in LEPREL1 1.2 Mb proximal to the region of the genome-wide association, which
was shown to be significantly associated with LS. LS-affected Lundehund harbored
the mutant LEPREL1:g.139212C>G genotype A/A whereas all controls of other breeds
showed the C/C wild type. In addition, ROH analysis for the Lundehund indicated a
high enrichment of genes in potential signatures of selection affecting protein
activation and immunoregulatory processes like NOD1 potentially involved in LS
breed disposition. CONCLUSIONS: Sequencing results for Lundehund specific traits
reveal a potential causative mutation for LS in the neuropeptide operating gene
LEPREL1 and suggests it as a precursor of the inflammatory process. Analyses of
ROH regions give an insight into the genetic background of characteristic traits
in the Lundehund that remain to be elucidated in the future.
PMID- 27485431
TI - Interprofessional and interdisciplinary simulation-based training leads to safe
sedation procedures in the emergency department.
AB - BACKGROUND: Sedation is a procedure required for many interventions in the
Emergency department (ED) such as reductions, surgical procedures or
cardioversions. However, especially under emergency conditions with high risk
patients and rapidly changing interdisciplinary and interprofessional teams, the
procedure caries important risks. It is thus vital but difficult to implement a
standard operating procedure for sedation procedures in any ED. Reports on both,
implementation strategies as well as their success are currently lacking. This
study describes the development, implementation and clinical evaluation of an
interprofessional and interdisciplinary simulation-based sedation training
concept. METHODS: All physicians and nurses with specialised training in
emergency medicine at the Berne University Department of Emergency Medicine
participated in a mandatory interdisciplinary and interprofessional simulation
based sedation training. The curriculum consisted of an individual self-learning
module, an airway skill training course, three simulation-based team training
cases, and a final practical learning course in the operating theatre. Before and
after each training session, self-efficacy, awareness of emergency procedures,
knowledge of sedation medication and crisis resource management were assessed
with a questionnaire. Changes in these measures were compared via paired tests,
separately for groups formed based on experience and profession. To assess the
clinical effect of training, we collected patient and team satisfaction as well
as duration and complications for all sedations in the ED within the year after
implementation. We further compared time to beginning of procedure, time for
duration of procedure and time until discharge after implementation with the one
year period before the implementation. Cohen's d was calculated as effect size
for all statistically significant tests. RESULTS: Fifty staff members (26 nurses
and 24 physicians) participated in the training. In all subgroups, there is a
significant increase in self-efficacy and knowledge with high effect size (d z =
1.8). The learning is independent of profession and experience level. In the
clinical evaluation after implementation, we found no major complications among
the sedations performed. Time to procedure significantly improved after the
introduction of the training (d = 0.88). DISCUSSION: Learning is independent of
previous working experience and equally effective in raising the self-efficacy
and knowledge in all professional groups. Clinical outcome evaluation confirms
the concepts safety and feasibility. CONCLUSION: An interprofessional and
interdisciplinary simulation-based sedation training is an efficient way to
implement a conscious sedation concept in an ED.
PMID- 27485432
TI - Effectiveness of conventional treatment using bulk-fill composite resin versus
Atraumatic Restorative Treatments in primary and permanent dentition: a pragmatic
randomized clinical trial.
AB - BACKGROUND: Clinical studies are being conducted in less strict conditions in
order to establish an adequate scientific basis for decision making. The aim of
this pragmatic randomized clinical trial is to evaluate the effectiveness of
single and multiple-surfaces restorations performed following the Atraumatic
Restorative Treatment (ART) premises compared with Conventional Treatment (CT)
using bulk fill composite restorations in primary and permanent teeth.
METHODS/DESIGN: A total of 1,214 5-to-13 year-old children with at least one
single or multiple-surface dentin caries lesion in primary or permanent molars
will be selected in public schools of Barueri-SP, Brazil. The participants will
be randomly assigned into 2 groups: CT (caries removal with bur and restoration
performed with ScotchbondTM Universal Adhesive system associated with Filtek Bulk
Fill - 3 M/ESPE) and ART (Caries removal with hand instruments and restoration
with high viscosity glass ionomer cement Ketac Molar Easy Mix - 3 M/ESPE). Ten
untrained dentists will perform the treatment in in dental offices located at
public schools. The restorations will be evaluated after 6, 12 and 24 months by
an independent trained and calibrated examiner. The restoration and tooth
survival, the cost-effectiveness analysis between the two groups and the
operators' preferences regarding the techniques will be also evaluated. Kaplan
Meier survival analysis and log-rank test will be applied for the restoration and
tooth survival. All the average event rates in the two groups will be modelled
and compared with a Cox proportional hazard shared frailty model since there is
an operator-cluster effect. The significance level for all analyses will be 5 %.
DISCUSSION: Our hypothesis is that despite similar expected effectiveness between
ART using high viscosity GIC and conventional treatment using bulk fill composite
resin when treating single or multiple-surface in posterior primary and permanent
teeth, ART will present superior cost-effectiveness. The results of this trial
will support decision-making by clinicians and policy makers. TRIAL REGISTRATION:
NCT02568917 . Registered on May 10th 2015.
PMID- 27485433
TI - The epidemiology of road traffic injury hotspots in Kigali, Rwanda from police
data.
AB - BACKGROUND: Road traffic injuries (RTIs) are the eighth-leading cause of death
worldwide, with low- and middle-income countries sharing a disproportionate
number of fatalities. African countries, like Rwanda, carry a higher burden of
these fatalities and with increased economic growth, these numbers are expected
to rise. We aim to describe the epidemiology of RTIs in Kigali Province, Rwanda
and create a hotspot map of crashes from police data. METHODS: Road traffic crash
(RTC) report data from January 1, 2013 to December 31, 2013 was collected from
Kigali Traffic Police. In addition to analysis of descriptive data, locations of
RTCs were mapped and analyzed through exploratory spatial data analysis to
determine hotspots. RESULTS: A total of 2589 of RTCs were reported with 4689
total victims. The majority of victims were male (94.7 %) with an average age of
35.9 years. Cars were the most frequent vehicle involved (43.8 %), followed by
motorcycles (14.5 %). Motorcycles had an increased risk of involvement in
grievous crashes and pedestrians and cyclists were more likely to have grievous
injuries. The hotspots identified were primarily located along the major roads
crossing Kigali and the two busiest downtown areas. CONCLUSIONS: Despite
significant headway by the government in RTC prevention, there continue to be
high rates of RTIs in Rwanda, specifically with young males and a vulnerable road
user population, such as pedestrians and motorcycle users. Improvements in police
data and reporting by laypersons could prove valuable for further geographic
information system analysis and efforts towards crash prevention and targeting
education to motorcycle taxis could help reduce RTIs in a severely affected
population.
PMID- 27485436
TI - Retraction Note to: Meta-analysis of the associations between TNF-alpha or IL-6
gene polymorphisms and susceptibility to lung cancer.
PMID- 27485434
TI - Evaluating the quality of shared decision making during the patient-carer
encounter: a systematic review of tools.
AB - BACKGROUND: The concept of shared decision making (SDM) has been developing in
many countries since the 1990s. The main challenge of SDM, based on the
principles of respect for the person's autonomy, is to improve patients'
participation, should they so wish, in decisions concerning their personal
health. To our knowledge, there is only one SDM evaluation tool validated in
metropolitan French that does not measure the entire SDM construct. The aim of
this review was to identify existing and validated SDM measurement tools to
determine which of them could be adapted in French to cover all the dimensions of
SDM. METHODS: A systematic literature review was conducted based on articles
found in the PubMed and PsycINFO bibliographic databases and published between
2010 and 2014. Studies were included if the main goal of the article was the
development and psychometric validation of an SDM measurement tool, not specific
to any given disease or situation, in English, French and Spanish. We used the
nine essential elements of the Makoul and Clayman's integrative model to describe
the different existing tools. RESULTS: Nineteen studies were included. Seven new
tools had been published since Scholl's previous review in 2011. We observed a
recent spread of the multi-appraiser approach, which combines points of view of
patients, healthcare professionals and sometimes external observers. Several
models were used for the development of the seven newly identified tools. None of
the identified tools assessed the nine elements of the Makoul's model. Three of
these elements, however, were systematically measured in each of the new tools:
"defining/explaining the problem", "patient values/preferences", and
"checking/clarifying understanding". CONCLUSIONS: We identified several
potentially interesting tools for the French context which could cover the whole
elements of Makoul's model. The next step will be the development of a French
language instrument based on these tools.
PMID- 27485437
TI - Patient preferences in allergy immunotherapy (AIT) in Germany - a discrete-choice
experiment.
AB - BACKGROUND: Allergic Rhinitis (AR) is a common disorder in Europe with Allergic
Asthma (AA) as a frequent comorbidity. Allergy immunotherapy (AIT) is the only
causal therapy of AR and AA, and can be administered as subcutaneous injections
at the physician or as sublingual drops or tablets at home. The usual treatment
duration is 3 years. OBJECTIVE: This study aimed to elicit patient preferences to
identify the AIT administration mode preferred by patients. METHODS: A discrete
choice-experiment (DCE) was developed to determine how people weight different
treatment options using a paper-based questionnaire from June to September 2014,
including 16 study centres. Main inclusion criteria: >18 years, grass, birch
and/or house dust mite AR with moderate to severe symptoms, AIT-naive and AIT
indicated. DCE-attributes were: Administration form, number and duration of
physician visits, frequency of life-threatening anaphylactic shocks, local side
effects and co-payments. RESULTS: Two-hundred thirty-nine subjects participated,
resulting in analysable 1842 choices. All attributes were significant predictors
for the treatment-choice. Ranked by importance, the following first three
attributes are most preferred by patients: 1(st) Number and duration of physician
visits: Fewer visits with shorter duration preferred (0.658*) 2(nd) Frequency of
life-threatening anaphylactic shocks: Lower risk of shocks preferred (0.285*)
3(rd) Local side-effects: Preference for rash/swelling on upper arm over
itching/swelling under the tongue (0.210*) (*coefficient-size represents relative
importance of the attributes) CONCLUSION: The most important attribute is the
number and duration of visits to a physician. A lower risk of life-threatening
anaphylactic shocks was ranked as the second whereas co-payments and
administration form play a limited role.
PMID- 27485438
TI - Benefit assessment in Germany: implications for price discounts.
AB - BACKGROUND: The AMNOG regulation, introduced in 2011 in Germany, changed the game
for new drugs. Now, the industry is required to submit a dossier to the GBA (the
central decision body in the German sickness fund system) to show additional
benefit. After granting the magnitude of the additional benefit by the GBA, the
manufacturer is entitled to negotiate the reimbursement price with the GKV-SV
(National Association of Statutory Health Insurance Funds). The reimbursement
price is defined as a discount on the drug price at launch. As the price or
discount negotiations between the manufacturers and the GKV-SV takes place behind
closed doors, the factors influencing the results of the negotiation are not
known. OBJECTIVES: The aim of this evaluation is to identify factors influencing
the results of the AMNOG price negotiation process. METHODS: The analysis was
based on a dataset containing detailed information on all assessments until the
end of 2015. A descriptive analysis was followed by an econometric analysis of
various potential factors (benefit rating, size of target population, deviating
from appropriate comparative therapy and incorporation of HRQoL-data). RESULTS:
Until December 2015, manufacturers and the GKV-SV finalized 96 negotiations in
193 therapeutic areas, based on assessment conducted by the GBA. The GBA has
granted an additional benefit to 100/193 drug innovations. Negotiated discount
was significantly higher for those drugs without additional benefit (p = 0.030)
and non-orphan drugs (p = 0.015). Smaller population size, no deviation from
recommended appropriate comparative therapy and the incorporation of HRQoL-data
were associated with a lower discount on the price at launch. However, neither a
uni- nor the multivariate linear regression showed enough power to predict the
final discount. CONCLUSIONS: Although the AMNOG regulation implemented binding
and strict rules for the benefit assessment itself, the outcome of the discount
negotiations are still unpredictable. Obviously, negotiation tactics, the current
political situation and soft factors seem to play a more influential role for the
outcome of the negotiations than the five hard and known factors analyzed in this
study. Further research is needed to evaluate additional factors.
PMID- 27485435
TI - Antiretroviral medication treatment for all HIV-infected individuals: a protocol
using innovative multilevel methodologies to evaluate New York City's universal
ART policy among problem substance users.
AB - BACKGROUND: The intersection of HIV-related health outcomes and problem substance
use has been well documented. New York City continues to be a focal point of the
U.S. HIV epidemic. In 2011, the NYC Department of Health and Mental Hygiene (NYC
DOHMH) issued a recommendation that all HIV infected individuals should be
offered antiretroviral therapy (ART) regardless of CD4 cell count or other
indicators of disease progression. This policy is based in the concept of
"treatment as prevention," in which providing ART to people living with HIV
(PLWH) greatly reduces the likelihood of HIV transmission, while also improving
individual health. The "ART for ALL" (AFA) study was designed to inform
modifications to and identify gaps in the implementation of universal ART, and
specifically to help guide allocation of resources to obtain local policy goals
for increasing viral suppression among PLWH who have problem substance use.
METHODS/DESIGN: The AFA Study is informed by two complementary frameworks:
Glasgow and colleagues' RE-AIM model, a multi-level framework developed to guide
the evaluation of implementation of new policies, and Bronfrenbrenner's
ecological systems model, which conceptualizes the bi-directional interplay
between people and their environment. Using multi-level data and mixed methods,
the primary aims of the AFA Study are to assess rates of viral load suppression,
using the NYC HIV Surveillance Registry, within 12 months of HIV diagnosis with
(a) yearly cohorts of high-risk-to-transmit, difficult-to-treat, substance using
patients recruited from NYC Sexually Transmitted Disease clinics and a large
detoxification unit and (b) yearly cohorts of all newly HIV diagnosed people in
NYC. Further goals include (c) recruiting cross-sectional samples of HIV/AIDS
service providers to assess ART initiation with problem substance users and d)
examining geographic factors that influence rates of viral load suppression. An
Implementation Collaborative Board meets regularly to guide study procedures and
interpret results. DISCUSSION: The AFA Study has the unique strength of accessing
and analyzing data at multiple levels using mixed methodology, taking advantage
of NYC DOHMH biomedical surveillance data. If successful, others may benefit from
lessons learned to inform local and state policies to improve the health of PLWH
and further reduce HIV transmission.
PMID- 27485439
TI - Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can
regulate CELF1 on binding to PRC2.
AB - BACKGROUND: Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis,
and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated
with several human cancers. However, the mechanisms of TUG1-involved regulation
remain largely unknown. METHODS: We examined the expressions of TUG1 in a cohort
of 89 patients with non-small cell lung cancer (NSCLC) to determine the
association between TUG1 expression and clinical parameters. We used circular
chromosome conformation capture (4C) coupled with next-generation sequencing to
explore the genome regions that interact with TUG1 and the TUG1-mediated
regulation. RESULTS: TUG1 was significantly downregulated, and the TUG1
downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and
tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted
the proliferation of NSCLC cells. According to the bioinformatic analysis result
of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were
identified. Among these candidate genes, CUGBP and Elav-like family member 1
(CELF1) are potential targets of TUG1 in-trans regulation. To confirm the
interaction between TUG1 and CELF1, relative expressions of CELF1 were examined
in TUG1 knockdown H520 cells; results showed that CELF1 was significantly
upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then
performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved
regulation mechanism reported in previous studies. The results demonstrated that
TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development
(EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay
revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992
bp upstream of the transcript start site. CONCLUSION: TUG1 is downregulated in
NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be
a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent
experiments showed that TUG1 RNA could bind to PRC2 in the promotor region of
CELF1 and negatively regulate CELF1 expressions in H520 cells. Our results may
facilitate developing new treatment modalities targeting TUG1/PRC2/CELF1
interactions in patients with NSCLC.
PMID- 27485442
TI - MetaCoMET: a web platform for discovery and visualization of the core microbiome.
AB - MOTIVATION: A key component of the analysis of microbiome datasets is the
identification of OTUs shared between multiple experimental conditions, commonly
referred to as the core microbiome. RESULTS: We present a web platform named
MetaCoMET that enables the discovery and visualization of the core microbiome and
provides a comparison of the relative abundance and diversity patterns between
subsets of samples within a microbiome dataset. MetaCoMET provides an efficient
and interactive graphical interface for analyzing each subset defined by the
union or disjunction of groups within the Venn diagram, and includes a graphical
taxonomy summary, alpha diversity metrics, Principal Coordinate analysis,
abundance-based heatmaps, and a chart indicating the geographic distribution of
each sample. AVAILABILITY AND IMPLEMENTATION: MetaCoMET is a user-friendly and
efficient web platform freely accessible at http://probes.pw.usda.gov/MetaCoMET
or http://aegilops.wheat.ucdavis.edu/MetaCoMET CONTACT: devin.coleman
derr@ars.usda.govSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27485441
TI - NET-GE: a web-server for NETwork-based human gene enrichment.
AB - MOTIVATION: Gene enrichment is a requisite for the interpretation of biological
complexity related to specific molecular pathways and biological processes.
Furthermore, when interpreting NGS data and human variations, including those
related to pathologies, gene enrichment allows the inclusion of other genes that
in the human interactome space may also play important key roles in the emergency
of the phenotype. Here, we describe NET-GE, a web server for associating
biological processes and pathways to sets of human proteins involved in the same
phenotype RESULTS: NET-GE is based on protein-protein interaction networks,
following the notion that for a set of proteins, the context of their specific
interactions can better define their function and the processes they can be
related to in the biological complexity of the cell. Our method is suited to
extract statistically validated enriched terms from Gene Ontology, KEGG and
REACTOME annotation databases. Furthermore, NET-GE is effective even when the
number of input proteins is small. AVAILABILITY AND IMPLEMENTATION: NET-GE web
server is publicly available and accessible at http://net
ge.biocomp.unibo.it/enrich CONTACT: gigi@biocomp.unibo.itSupplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 27485440
TI - Role of bioactive fatty acids in nonalcoholic fatty liver disease.
AB - Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in
hepatocytes, and a strong association with nutritional factors. Dietary fatty
acids are classified according to their biochemical properties, which confer
their bioactive roles. Monounsaturated fatty acids have a dual role in various
human and murine models. In contrast, polyunsaturated fatty acids exhibit
antiobesity, anti steatosic and anti-inflammatory effects. The combination of
these forms of fatty acids-according to dietary type, daily intake and the
proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A
chemosensory rather than a nutritional role makes bioactive fatty acids possible
biomarkers for NAFLD. Bioactive fatty acids provide health benefits through
modification of fatty acid composition and modulating the activity of liver cells
during liver fibrosis. More and better evidence is necessary to elucidate the
role of bioactive fatty acids in nutritional and clinical treatment strategies
for patients with NAFLD.
PMID- 27485443
TI - An efficient method to estimate the optimum regularization parameter in RLDA.
AB - MOTIVATION: The biomarker discovery process in high-throughput genomic profiles
has presented the statistical learning community with a challenging problem,
namely learning when the number of variables is comparable or exceeding the
sample size. In these settings, many classical techniques including linear
discriminant analysis (LDA) falter. Poor performance of LDA is attributed to the
ill-conditioned nature of sample covariance matrix when the dimension and sample
size are comparable. To alleviate this problem, regularized LDA (RLDA) has been
classically proposed in which the sample covariance matrix is replaced by its
ridge estimate. However, the performance of RLDA depends heavily on the
regularization parameter used in the ridge estimate of sample covariance matrix.
RESULTS: We propose a range-search technique for efficient estimation of the
optimum regularization parameter. Using an extensive set of simulations based on
synthetic and gene expression microarray data, we demonstrate the robustness of
the proposed technique to Gaussianity, an assumption used in developing the core
estimator. We compare the performance of the technique in terms of accuracy and
efficiency with classical techniques for estimating the regularization parameter.
In terms of accuracy, the results indicate that the proposed method vastly
improves on similar techniques that use classical plug-in estimator. In that
respect, it is better or comparable to cross-validation-based search strategies
while, depending on the sample size and dimensionality, being tens to hundreds of
times faster to compute. AVAILABILITY AND IMPLEMENTATION: The source code is
available at https://github.com/danik0411/optimum-rlda CONTACT:
amin.zollanvari@nu.edu.kzSupplementary information: Supplementary materials are
available at Bioinformatics online.
PMID- 27485444
TI - Predicting G protein-coupled receptor downstream signaling by tissue expression.
AB - MOTIVATION: G protein-coupled receptors (GPCRs) are central to how cells respond
to their environment and a major class of pharmacological targets. However,
comprehensive knowledge of which pathways are activated and deactivated by these
essential sensors is largely unknown. To better understand the mechanism of GPCR
signaling system, we integrated five independent genome-wide expression datasets,
representing 275 human tissues and cell lines, with protein-protein interactions
and functional pathway data. RESULTS: We found that tissue-specificity plays a
crucial part in the function of GPCR signaling system. Only a few GPCRs are
expressed in each tissue, which are coupled by different combinations of G
proteins or beta-arrestins to trigger specific downstream pathways. Based on this
finding, we predicted the downstream pathways of GPCR in human tissues and
validated our results with L1000 knockdown data. In total, we identified 154,988
connections between 294 GPCRs and 690 pathways in 240 tissues and cell types.
AVAILABILITY AND IMPLEMENTATION: The source code and results supporting the
conclusions of this article are available at
http://tatonettilab.org/resources/GOTE/source_code/ CONTACT:
nick.tatonetti@columbia.eduSupplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 27485445
TI - NRGC: a novel referential genome compression algorithm.
AB - MOTIVATION: Next-generation sequencing techniques produce millions to billions of
short reads. The procedure is not only very cost effective but also can be done
in laboratory environment. The state-of-the-art sequence assemblers then
construct the whole genomic sequence from these reads. Current cutting edge
computing technology makes it possible to build genomic sequences from the
billions of reads within a minimal cost and time. As a consequence, we see an
explosion of biological sequences in recent times. In turn, the cost of storing
the sequences in physical memory or transmitting them over the internet is
becoming a major bottleneck for research and future medical applications. Data
compression techniques are one of the most important remedies in this context. We
are in need of suitable data compression algorithms that can exploit the inherent
structure of biological sequences. Although standard data compression algorithms
are prevalent, they are not suitable to compress biological sequencing data
effectively. In this article, we propose a novel referential genome compression
algorithm (NRGC) to effectively and efficiently compress the genomic sequences.
RESULTS: We have done rigorous experiments to evaluate NRGC by taking a set of
real human genomes. The simulation results show that our algorithm is indeed an
effective genome compression algorithm that performs better than the best-known
algorithms in most of the cases. Compression and decompression times are also
very impressive. AVAILABILITY AND IMPLEMENTATION: The implementations are freely
available for non-commercial purposes. They can be downloaded from:
http://www.engr.uconn.edu/~rajasek/NRGC.zip CONTACT: rajasek@engr.uconn.edu.
PMID- 27485447
TI - ReactPRED: a tool to predict and analyze biochemical reactions.
AB - MOTIVATION: Biochemical pathways engineering is often used to synthesize or
degrade target chemicals. In silico screening of the biochemical transformation
space allows predicting feasible reactions, constituting these pathways. Current
enabling tools are customized to predict reactions based on pre-defined
biochemical transformations or reaction rule sets. Reaction rule sets are usually
curated manually and tailored to specific applications. They are not exhaustive.
In addition, current systems are incapable of regulating and refining data with
an aim to tune specificity and sensitivity. A robust and flexible tool that
allows automated reaction rule set creation along with regulated pathway
prediction and analyses is a need. ReactPRED aims to address the same. RESULTS:
ReactPRED is an open source flexible and customizable tool enabling users to
predict biochemical reactions and pathways. The tool allows automated reaction
rule creation from a user defined reaction set. Additionally, reaction rule
degree and rule tolerance features allow refinement of predicted data. It is
available as a flexible graphical user interface and a console application.
AVAILABILITY AND IMPLEMENTATION: ReactPRED is available at:
https://sourceforge.net/projects/reactpred/ CONTACT: anirban.b@samsung.com or
ty76.kim@samsung.comSupplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 27485446
TI - HiPub: translating PubMed and PMC texts to networks for knowledge discovery.
AB - We introduce HiPub, a seamless Chrome browser plug-in that automatically
recognizes, annotates and translates biomedical entities from texts into networks
for knowledge discovery. Using a combination of two different named-entity
recognition resources, HiPub can recognize genes, proteins, diseases, drugs,
mutations and cell lines in texts, and achieve high precision and recall. HiPub
extracts biomedical entity-relationships from texts to construct context-specific
networks, and integrates existing network data from external databases for
knowledge discovery. It allows users to add additional entities from related
articles, as well as user-defined entities for discovering new and unexpected
entity-relationships. HiPub provides functional enrichment analysis on the
biomedical entity network, and link-outs to external resources to assist users in
learning new entities and relations. AVAILABILITY AND IMPLEMENTATION: HiPub and
detailed user guide are available at http://hipub.korea.ac.kr CONTACT:
kangj@korea.ac.kr, aikchoon.tan@ucdenver.edu SUPPLEMENTARY INFORMATION:
Supplementary data are available at Bioinformatics online.
PMID- 27485448
TI - Erratum: Finite particle size drives defect-mediated domain structures in
strongly confined colloidal liquid crystals.
PMID- 27485449
TI - Amarogentin ameliorates diabetic disorders in animal models.
AB - Amarogentin is a bitter-tasting secoiridoid glycoside isolated from an herb.
Inhibition of aldose reductase by amarogentin has been documented as an
antidiabetic action. However, the mechanisms of action of amarogentin in diabetic
disorders remain unknown. The present study employed streptozotocin-induced type
1 diabetic (T1DM) rats to investigate the antihyperglycemic action of
amarogentin. Changes in the protein expression of glucose transporter 4 (GLUT4)
and phosphoenolpyruvate carboxykinase (PEPCK) in skeletal muscle and liver,
respectively, were also detected by Western blotting. Additionally, a type 2
diabetes (T2DM) animal model induced using a fructose-rich diet was also applied
to assess the effect of amarogentin on insulin resistance according to the
homeostasis model assessment-insulin resistance (HOMA-IR). Amarogentin dose
dependently attenuated hyperglycemia in the T1DM rats lacking insulin. The action
of amarogentin was further supported in rats administered the oral glucose
tolerance test. Western blotting showed that amarogentin reversed the decreased
GLUT4 level in skeletal muscle and reduced the elevated PEPCK expression in
livers isolated from the T1DM rats. Moreover, amarogentin decreased the HOMA-IR
and increased insulin sensitivity in the T2DM rats. These data show that
amarogentin may ameliorate glucose homeostasis in diabetic rats, indicating its
potential for future development as an antidiabetic drug.
PMID- 27485450
TI - Metastatic Progression of Prostate Cancer Is Mediated by Autonomous Binding of
Galectin-4-O-Glycan to Cancer Cells.
AB - Metastatic prostate cancer continues to pose a difficult therapeutic challenge.
Prostate cancer progression is associated with aberrant O-glycosylation of cancer
cell surface receptors, but the functional impact of such events is uncertain.
Here we report spontaneous metastasis of human prostate cancer xenografts that
express high levels of galectin-4 along with genetic signatures of EGFR-HER2
signaling and O-glycosylation. Galectin-4 expression in clinical specimens of
prostate cancer correlated with poor patient survival. Galectin-4 binding to
multiple receptor tyrosine kinases stimulated their autophosphorylation,
activated expression of pERK, pAkt, fibronectin, and Twist1, and lowered
expression of E-cadherin, thereby facilitating epithelial-mesenchymal transition,
invasion, and metastasis. In vivo investigations established that galectin-4
expression enabled prostate cancer cells to repopulate tumors in orthotopic and
heterotopic tissues. Notably, these effects of galectin-4 relied upon O
glycosylation mediated by C1GALT1, a galactosyltransferase implicated in other
cancers. Parallel changes in galectin-4 and O-glycosylation triggered aberrant
receptor signaling and more aggressive invasive character in prostate cancer
cells, which through better survival in the circulation also contributed to the
bulk cell progeny of distal tumors. Our findings establish galectin-4 and C1GALT1
mediated glycosylation in a signaling axis that is activated during prostate
cancer progression, with implications for therapeutic targeting of advanced
metastatic disease. Cancer Res; 76(19); 5756-67. (c)2016 AACR.
PMID- 27485451
TI - Recurrent PPP2R1A Mutations in Uterine Cancer Act through a Dominant-Negative
Mechanism to Promote Malignant Cell Growth.
AB - Somatic missense mutations in the Ser/Thr protein phosphatase 2A (PP2A) Aalpha
scaffold subunit gene PPP2R1A are among the few genomic alterations that occur
frequently in serous endometrial carcinoma (EC) and carcinosarcoma, two
clinically aggressive subtypes of uterine cancer with few therapeutic options.
Previous studies reported that cancer-associated Aalpha mutants exhibit defects
in binding to other PP2A subunits and contribute to cancer development by a
mechanism of haploinsufficiency. Here we report on the functional significance of
the most recurrent PPP2R1A mutations in human EC, which cluster in Aalpha HEAT
repeats 5 and 7. Beyond predicted loss-of-function effects on the formation of a
subset of PP2A holoenzymes, we discovered that Aalpha mutants behave in a
dominant-negative manner due to gain-of-function interactions with the PP2A
inhibitor TIPRL1. Dominant-negative Aalpha mutants retain binding to specific
subunits of the B56/B' family and form substrate trapping complexes with impaired
phosphatase activity via increased recruitment of TIPRL1. Accordingly,
overexpression of the Aalpha mutants in EC cells harboring wild-type PPP2R1A
increased anchorage-independent growth and tumor formation, and triggered
hyperphosphorylation of oncogenic PP2A-B56/B' substrates in the GSK3beta, Akt,
and mTOR/p70S6K signaling pathways. TIPRL1 silencing restored GSK3beta
phosphorylation and rescued the EC cell growth advantage. Our results reveal how
PPP2R1A mutations affect PP2A function and oncogenic signaling, illuminating the
genetic basis for serous EC development and its potential control by rationally
targeted therapies. Cancer Res; 76(19); 5719-31. (c)2016 AACR.
PMID- 27485452
TI - Integrating evidence-based practices for increasing cancer screenings in safety
net health systems: a multiple case study using the Consolidated Framework for
Implementation Research.
AB - BACKGROUND: Implementing evidence-based practices (EBPs) to increase cancer
screenings in safety net primary care systems has great potential for reducing
cancer disparities. Yet there is a gap in understanding the factors and
mechanisms that influence EBP implementation within these high-priority systems.
Guided by the Consolidated Framework for Implementation Research (CFIR), our
study aims to fill this gap with a multiple case study of health care safety net
systems that were funded by an American Cancer Society (ACS) grants program to
increase breast and colorectal cancer screening rates. The initiative funded 68
safety net systems to increase cancer screening through implementation of
evidence-based provider and client-oriented strategies. METHODS: Data are from a
mixed-methods evaluation with nine purposively selected safety net systems. Fifty
two interviews were conducted with project leaders, implementers, and ACS staff.
Funded safety net systems were categorized into high-, medium-, and low
performing cases based on the level of EBP implementation. Within- and cross-case
analyses were performed to identify CFIR constructs that influenced level of EBP
implementation. RESULTS: Of 39 CFIR constructs examined, six distinguished levels
of implementation. Two constructs were from the intervention characteristics
domain: adaptability and trialability. Three were from the inner setting domain:
leadership engagement, tension for change, and access to information and
knowledge. Engaging formally appointed internal implementation leaders, from the
process domain, also distinguished level of implementation. No constructs from
the outer setting or individual characteristics domain differentiated systems by
level of implementation. CONCLUSIONS: Our study identified a number of
influential CFIR constructs and illustrated how they impacted EBP implementation
across a variety of safety net systems. Findings may inform future dissemination
efforts of EBPs for increasing cancer screening in similar settings. Moreover,
our analytic approach is similar to previous case studies using CFIR and hence
could facilitate comparisons across studies.
PMID- 27485453
TI - Cost analysis of a randomized stem cell mobilization study in multiple myeloma.
AB - Upfront autologous stem cell transplantation (ASCT) is the standard therapy for
younger multiple myeloma (MM) patients. MM patients usually undergo stem cell
mobilization with cyclophosphamide (CY) followed by granulocyte colony
stimulating factor (G-CSF), or with G-CSF alone. A limited number of randomized
studies are available comparing costs of different mobilization strategies.
Eighty transplant-eligible patients aged up to 70 years with untreated MM were
included in this prospective study. The patients were treated with RVD induction
for three 21-day cycles and randomized 1:1 at inclusion into one of the two
mobilization arms CY 2 g/m(2) + G-CSF [arm A] vs. G-CSF alone [arm B]. Plerixafor
was given according to a specific algorithm if needed. Sixty-nine patients who
received mobilization followed by blood graft collection were included in the
cost analysis. The median total costs of the mobilization phase were
significantly higher in arm A than in arm B (3855 ? vs. 772 ?, p <= 0.001). The
cumulative median cost of the mobilization and collection phases was
significantly lower in arm B than in arm A (8524 ? vs. 11,622 ?, p = 0.012).
There was no significant difference between the arms in the total median costs of
ASCT (n = 59) (34,997 ? in arm A vs. 31,981 ? in arm B, p = 0.118). Mobilization
with G-CSF alone seems to be a preferable mobilization method for MM patients in
terms of mobilization and apheresis costs. In addition, it requires less hospital
resource utilization.
PMID- 27485454
TI - R-CVP regimen is active in frail elderly patients aged 80 or over with diffuse
large B cell lymphoma.
AB - Patients aged 80 or over with diffuse large B cell lymphoma (DLBCL) often have
comorbidities that increase drug toxicity and prevent the use of otherwise
optimal treatment. We performed a retrospective analysis of 43 patients aged 80
or over (median age: 83; range: 80-93) unable to receive treatment with
anthracyclines, at diagnosis of DLBCL, treated with an R-CVP treatment (standard
R-CHOP without doxorubicin). The patients had one or more comorbidities: 18
patients (41.9 %) had a performance status (PS) of 3; 23 patients (53.5 %) had
low creatinine clearance; 12 patients (27.9 %) had low left ventricular ejection
fraction; seven patients (16.3 %) had poor hepatic function; and 26 patients
(60.5 %) had a Charlson index score >=4. Thirty patients (70 %) had two or three
adverse factors according to the age-adjusted International Prognostic Index.
Twenty-five patients (58.1 %) received eight cycles of R-CVP, but the full eight
cycles could not be given to 18 patients (41.9 %). The OR rate was 58.1 % (CR
37.2 %). There were 34 deaths (79 %) during treatment and follow-up. Ten patients
(23.3 %) died early from toxicity before interim evaluation; all had PS 3. The
median follow-up of surviving patients was 52.6 months. The overall 2-year
survival rate was 31.9 % and the median OS was 12.6 months. The median OS for
patients who completed the entire treatment was 26.4 months. The median PFS was
11.2 months. In multivariate analyses, OS was only affected by performance status
>=2 and Charlson index score >=4. The R-CVP regimen can be active in elderly
frail patients aged 80 or more with DLBCL, but systematic geriatric assessment is
required so that those unsuitable for chemotherapy are excluded.
PMID- 27485455
TI - Clinical characteristics and risk factors of Intracranial hemorrhage in patients
following allogeneic hematopoietic stem cell transplantation.
AB - Intracranial hemorrhage (ICH) is one of the most life-threatening neurological
complications after allogeneic hematopoietic stem cell transplantation. Although
cerebral complications and its causes after allo-HSCT are well documented,
assessment of the incidence and risk factors of intracranial hemorrhage following
allo-HSCT are less discussed. A nested case-control study was conducted involving
160 subjects drawn from 2169 subjects who underwent HSCT at Peking University
People's Hospital between 2004 and 2014. Thirty-two patients (1.5 %) with ICH
were identified, and 128 controls were matched for age, gender, transplantation
type, and time of transplantation. Intracranial hemorrhage was identified by CT
scan and/or MRI by searching hospital records. Among the 32 ICH patients, 27
(82.9 %) developed intraparenchymal hemorrhages (IPH), 2 cases (5.7 %) suffered
subdural hematomas (SDH), and 3 cases (8.6 %) had multiple hemorrhage lesions in
the brain parenchyma. The median time of appearance for cerebral hemorrhages was
147.5 days. Multivariate analysis showed that systemic infections (hazard ratio
2.882, 95 % confidence interval 1.231-6.746), platelet count (5.894, 1.145
30.339), and fibrinogen levels (3.611, 1.528-8.532) were independent risk factors
for intracranial hemorrhage among HSCT patients. The cumulative survival rate in
the intracranial hemorrhage and control groups were 43.3 and 74.7 % (P = .001),
respectively. Intracranial hemorrhage is associated with high mortality and a
decreased overall survival rate. Systemic infections, platelet count, and
fibrinogen levels were individual independent risk factors.
PMID- 27485456
TI - Capsaicin for Rhinitis.
AB - Rhinitis is a multifactorial disease characterized by symptoms of sneezing,
rhinorrhea, postnasal drip, and nasal congestion. Non-allergic rhinitis is
characterized by rhinitis symptoms without systemic sensitization of infectious
etiology. Based on endotypes, we can categorize non-allergic rhinitis into an
inflammatory endotype with usually eosinophilic inflammation encompassing at
least NARES and LAR and part of the drug induced rhinitis (e.g., aspirin
intolerance) and a neurogenic endotype encompassing idiopathic rhinitis,
gustatory rhinitis, and rhinitis of the elderly. Patients with idiopathic
rhinitis have a higher baseline TRPV1 expression in the nasal mucosa than healthy
controls. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is the active component of
chili peppers, plants of the genus Capsicum. Capsaicin is unique among naturally
occurring irritant compounds because the initial neuronal excitation evoked by it
is followed by a long-lasting refractory period, during which the previously
excited neurons are no longer responsive to a broad range of stimuli. Patients
with idiopathic rhinitis benefit from intranasal treatment with capsaicin.
Expression of TRPV1 is reduced in patients with idiopathic rhinitis after
capsaicin treatment. Recently, in a Cochrane review, the effectiveness of
capsaicin in the management of idiopathic rhinitis was evaluated and the authors
concluded that given that many other options do not work well in non-allergic
rhinitis, capsaicin is a reasonable option to try under physician supervision.
Capsaicin has not been shown to be effective in allergic rhinitis nor in other
forms of non-allergic rhinitis like the inflammatory endotypes or other
neurogenic endotypes like rhinitis of the elderly or smoking induced rhinitis.
PMID- 27485457
TI - Nutritional care of cancer patients: a survey on patients' needs and medical care
in reality.
AB - PURPOSE: Cancer patients represent a patient group with a wide-range of nutrition
related problems which are often under-recognized and undertreated. In order to
assess the status quo of nutritional care in Germany, we conducted a survey among
patients with different types of cancer. METHODS: A standardized questionnaire
was distributed online by two national umbrella organizations for self-help
groups. RESULTS: 1335 participants completed the questionnaire. 69 % of the
participants reported having received information on nutrition and/or specific
nutrition-related symptoms. Most often this information was derived from print
media (68.5 %) or from within self-help groups (58.7 %). 57.0 % of participants
reported having had questions concerning nutrition and/or problems with food
intake. most frequently named topics of interest were "healthy diet" (35.0 %)
weakness/fatigue (24.3 %), dietary supplements (21.3 %) and taste changes (19.8
%). Nutrition information was most often provided by dietitians (38.7 %) followed
by physicians (9.8 %). Women reported receiving nutrition counseling in the
hospital nearly twice as often as men (12.5 % versus 5.7 %; p < 0.001). A quarter
of the patients (24.1 %) reported using dietary supplements and patients who had
received some sort of nutrition information more often reported using supplements
(p < 0.001). CONCLUSION: Nutrition is an essential element in cancer care and
patients report a high interest and need: Yet, many patients do not have access
to high quality nutrition therapy during and after cancer therapy. IMPLICATIONS
FOR CANCER SURVIVORS: With respect to survival and quality of life, increasing
the availability and resources for provision of evidence based nutrition
information seems mandatory.
PMID- 27485459
TI - Genetics of primary hyperaldosteronism.
AB - Hypertension is a common medical condition and affects approximately 20% of the
population in developed countries. Primary aldosteronism is the most common form
of secondary hypertension and affects 8-13% of patients with hypertension. The
two most common causes of primary aldosteronism are aldosterone-producing adenoma
and bilateral adrenal hyperplasia. Familial hyperaldosteronism types I, II and
III are the known genetic syndromes, in which both adrenal glands produce
excessive amounts of aldosterone. However, only a minority of patients with
primary aldosteronism have one of these syndromes. Several novel susceptibility
genes have been found to be mutated in aldosterone-producing adenomas: KCNJ5,
ATP1A1, ATP2B3, CTNNB1, CACNA1D, CACNA1H and ARMC5 This review describes the
genes currently known to be responsible for primary aldosteronism, discusses the
origin of aldosterone-producing adenomas and considers the future clinical
implications based on these novel insights.
PMID- 27485458
TI - Functional Recovery from Neural Stem/Progenitor Cell Transplantation Combined
with Treadmill Training in Mice with Chronic Spinal Cord Injury.
AB - Most studies targeting chronic spinal cord injury (SCI) have concluded that
neural stem/progenitor cell (NS/PC) transplantation exerts only a subclinical
recovery; this in contrast to its remarkable effect on acute and subacute SCI. To
determine whether the addition of rehabilitative intervention enhances the effect
of NS/PC transplantation for chronic SCI, we used thoracic SCI mouse models to
compare manifestations secondary to both transplantation and treadmill training,
and the two therapies combined, with a control group. Significant locomotor
recovery in comparison with the control group was only achieved in the combined
therapy group. Further investigation revealed that NS/PC transplantation improved
spinal conductivity and central pattern generator activity, and that treadmill
training promoted the appropriate inhibitory motor control. The combined therapy
enhanced these independent effects of each single therapy, and facilitated
neuronal differentiation of transplanted cells and maturation of central pattern
generator activity synergistically. Our data suggest that rehabilitative
treatment represents a therapeutic option for locomotor recovery after NS/PC
transplantation, even in chronic SCI.
PMID- 27485460
TI - Perspectives for immunotherapy in endocrine cancer.
AB - The fight against cancer has seen major breakthroughs in recent years. More than
a decade ago, tyrosine kinase inhibitors targeting constitutively activated
signaling cascades within the tumor inaugurated a new era of oncological therapy.
Recently, immunotherapy with immune checkpoint inhibitors has started to
revolutionize the treatment of several malignancies, most notably malignant
melanoma, leading to the renaissance and the long-awaited breakthrough of
immunooncology. This review provides an overview of the basis of immunotherapy
from its initial concepts of anti-tumor immunity and cell-based therapy to the
development of immune checkpoint inhibitors and discusses published studies and
the perspectives of immunooncology for the treatment of endocrine malignancies.
PMID- 27485461
TI - A HELLP syndrome complicates a gestational trophoblastic neoplasia in a
perimenopausal woman: a case report.
AB - BACKGROUND: HELLP syndrome is a combination of symptoms described as hemolysis,
elevated liver enzymes and low platelets, that complicates 0.01-0.6 % of
pregnancies. HELLP syndrome has been scarcely reported associated with partial
moles, another rare complication of pregnancy. This manuscript describes the only
reported case of HELLP syndrome associated with a complete invasive hydatiform
mole. CASE PRESENTATION: We report a perimenopausal patient in prolonged
remission from an uncommon high-risk invasive complete mole. The diagnosis was
set in a context of early onset preeclampsia and HELLP syndrome. The development
of life-threatening complications required primary hysterectomy. Postoperative
hCG quickly returned to normal with EMA/CO multi-agent chemotherapy. CONCLUSION:
Our patient is in prolonged remission from a complete mole complicated with EOP
and HELLP syndrome. This exceptional case of complicated gestational
trophoblastic neoplasia reflects a very rare condition in which several risk
factors for placental ischemia are associated. Emergency hysterectomy should be
considered as salvage initial treatment in such life-threatening situations.
PMID- 27485462
TI - Can I get me out of my head? Exploring strategies for controlling the self
referential aspects of the mind-wandering state during reading.
AB - Trying to focus on a piece of text and keep unrelated thoughts at bay can be a
surprisingly futile experience. The current study explored the effects of
different instructions on participants' capacity to control their mind-wandering
and maximize reading comprehension, while reading. Participants were instructed
to (a) enhance focus on what was read (external) or (b) enhance meta-awareness of
mind-wandering (internal). To understand when these strategies were important, we
induced a state of self-focus in half of our participants at the beginning of the
experiment. Results replicated the negative association between mind-wandering
and comprehension and demonstrated that both internal and external instructions
impacted on the efficiency of reading following a period of induced self-focus.
Techniques that foster meta-awareness improved task focus but did so at the
detriment of reading comprehension, while promoting a deeper engagement while
reading improved comprehension with no changes in reported mind-wandering. These
data provide insight into how we can control mind-wandering and improve
comprehension, and they underline that a state of self-focus is a condition under
which they should be employed. Furthermore, these data support component process
models that propose that the self-referent mental contents that arise during mind
wandering are distinguishable from those processes that interfere with
comprehension.
PMID- 27485463
TI - Physical activity is associated with reduced fatigue in adults living with
HIV/AIDS.
AB - AIMS: The aim of this study was to describe the relationships among home-based
physical activity, fatigue, sleep, gender and quality of life in people living
with HIV/AIDS BACKGROUND: Fatigue is a common and distressing symptom among
people living with HIV/AIDS. Few interventions exist that effectively reduce
fatigue in this population. Physical activity has shown promise to reduce fatigue
in other populations, but its impact on fatigue in HIV/AIDS has not yet been
explored. DESIGN: This study was conducted using a prospective, descriptive
cohort design. METHODS: Overall, 90 adults living with HIV/AIDS completed cross
sectional measures. Home-based physical activity was measured using a 7-day self
report diary. Fatigue was measured using the self-reported HIV-Related Fatigue
Scale. Sleep was assessed using wrist actigraphy and quality of life was assessed
using the HIV-Associated Quality of Life Scale. Data were collected from December
2012-April 2013 and analysed using correlations and multiple linear regression.
RESULTS: The number of minutes of home-based physical activity was significantly
associated with reduced fatigue among people living with HIV/AIDS. In addition,
increased fatigue was associated with decreased quality of life. No associations
were found among fatigue, sleep or gender. CONCLUSIONS: Our study demonstrates
that physical activity in the home setting is an effective strategy to reduce
fatigue among people living with HIV/AIDS. Future work developing and testing
interventions to improve home-based physical activity in this population is
needed.
PMID- 27485464
TI - A Brief Community-Based Nutrition Education Intervention Combined With Food
Baskets Can Increase Fruit and Vegetable Consumption Among Low-Income Latinos.
AB - OBJECTIVE: To evaluate the impact of an 8-week community-based nutrition
education program combined with food baskets on fruit and vegetable consumption
(FVC) among Latinos. DESIGN: Pre-post intervention study assessing perceived
barriers, knowledge, food efficacy, food outcomes, and FVC, using mixed methods
(quantitative and qualitative). SETTING: Participants' recruitment and data
collection took place in the Seattle Metropolitan area from September 2012 to
July 2013. PARTICIPANTS: Participants' (n = 40) mean age was 37.8 (+/-10.5)
years. Participants were mostly women, from Mexico, uninsured, low income, and
overweight or obese. INTERVENTION: Nuestras Comidas was developed through the use
of the Social Cognitive Theory and focused on increasing behavioral capability,
food efficacy, food outcomes, and FVC. MAIN OUTCOME MEASURE: Dependent variables
were knowledge, perceived barriers, food efficacy, food outcomes, and FVC.
Independent variable was the intervention (pre-post). STATISTICAL ANALYSES: A
McNemar exact test was computed for categorical variables and Wilcoxon signed
rank test and paired t test for continuous variables. Focus group data were
analyzed by identifying common themes. RESULTS: Participation in the intervention
was significantly associated with increased knowledge, food efficacy, and
vegetable consumption. CONCLUSIONS AND IMPLICATIONS: A brief nutrition education
intervention combined with food baskets can improve healthy eating among Latinos.
PMID- 27485466
TI - Maternal micronutrient consumption periconceptionally and during pregnancy: a
prospective cohort study.
AB - OBJECTIVE: To examine overall micronutrient intake periconceptionally and
throughout pregnancy in a population-based cohort of Australian women. DESIGN: In
a prospective cohort study, micronutrient dosages were extracted from self
reported maternal supplement use, recorded pre-conception, and for each trimester
of pregnancy. A food frequency scale (DQESv2) captured usual maternal diet for
gestational weeks 14-26. The influence of sociodemographic and lifestyle factors
associated with supplement use was examined using logistic regression, and
changes in micronutrient intakes prior to and throughout pregnancy were assessed
using repeated-measures ANOVA analyses. SETTING: Metropolitan hospital sites in
Melbourne, Australia. SUBJECTS: Women with a viable singleton pregnancy were
recruited at less than 19 weeks' gestation (n 2146). RESULTS: Compared with non
users, women using supplements during pregnancy were more likely to have planned
their pregnancy, be >25 years old, primiparous, Caucasian, non-smokers, have a
tertiary education and be consuming a folate-rich diet. Intakes of folate, Fe and
Zn were significantly lower in the periconceptional period, compared with other
periods (P<0.001). Intakes below Recommended Daily Intake levels were common both
periconceptionally and throughout pregnancy, with 19-46 % of women not meeting
the Recommended Daily Intake for folate, 68-82 % for Fe and 17-36 % for Zn.
Conversely, 15-19 % of women consumed beyond the recommended Upper Limit for
folate and 11-24 % for Fe. CONCLUSIONS: The study highlights the need for
improved public health education on nutritional needs during pregnancy,
especially among women with lower educational achievements and income.
PMID- 27485467
TI - Lessons learnt from the radiological measures performed by the Radiological
Emergency Network of Extremadura in the International Emergency Exercise CURIEX
2013.
AB - In late 2013 (5th-7th of November), the Caceres Urgent Response International
Exercise (CURIEX 2013) took place to test the Nuclear Emergency Plan of Caceres
(PENCA) with the collaboration of both national and international support teams.
The theme of the exercise was the simulation of a nuclear accident at the Almaraz
Nuclear Power Plant located in Extremadura (Spain) with release of radioactive
plume. From the point of view of radioactive contamination, the CURIEX exercise
objective was to assess the capability of the different radiological teams to
quantify the radioactive impact that would occur in this environment, a goal in
which the Radiological Emergency Network of Extremadura (RARE) is directly
implicated. The present paper analyses in detail the environmental radiological
and dosimetrical results obtained by the Radiological Emergency Network of
Extremadura during the CURIEX exercise. The rapid radioactivity measurement
techniques on air and soil samples performed by the RARE's mobile lab involves
great uncertainties. However, the results show a relative good effectiveness both
in dose rate car-borne measurements and gamma soil spectrometry with
uncertainties over 40%. It also shows a good correlation between the dose rate
values measured by car-borne apparatus and those calculated from gamma
spectrometry measurements. The capability of the RARE's facilities are evaluated
in both the measurements, showing whether or not there is a radiological problem,
and the transmission of that data to the decision centres in the shortest time.
Although the results were highly satisfactory, some shortcomings were detected
and therefore some improvements are proposed in the paper, in order to achieve a
greater capacity in response to an event with the characteristics simulated in
the CURIEX exercise.
PMID- 27485465
TI - ADHD and Sleep Quality: Longitudinal Analyses From Childhood to Early Adulthood
in a Twin Cohort.
AB - Attention-deficit/hyperactivity disorder (ADHD) is associated with poor sleep
quality, but there is more to learn about the longitudinal association and
aetiology of this association. We investigated the following: (a) Is there an
association between childhood ADHD and poor sleep quality in young adulthood? (b)
Is this driven by the long-term effects of childhood ADHD or concurrent
associations with ADHD in young adulthood? (c) To what extent do genetic and
environmental influences explain the overlap between symptoms of ADHD and poor
sleep quality? Participants were from the Environmental Risk Longitudinal Twin
Study of 2,232 twin children born in the United Kingdom in 1994-1995. We
ascertained ADHD diagnoses at ages 5, 7, 10, 12, and 18. We assessed sleep
quality using the Pittsburgh Sleep Quality Index at age 18. We used regression
models to examine longitudinal associations and bivariate twin modelling to test
genetic and environmental influences. Children with ADHD had poorer sleep quality
in young adulthood, but only if their ADHD persisted. Adults with ADHD had more
sleep problems than those without ADHD, over and above psychiatric comorbidity
and maternal insomnia. ADHD and sleep problems in young adulthood were associated
because of genetic (55%) and nonshared environmental influences (45%). Should
ADHD remit, children with ADHD do not appear to have an increased risk of later
sleep problems. Good quality sleep is important for multiple areas of
functioning, and a better understanding of why adults with ADHD have poorer sleep
quality will further the goal of improving treatments.
PMID- 27485468
TI - Cardio-metabolic responses during horse riding at three different speeds.
AB - PURPOSE: The purpose of the present investigation was to study the metabolic
demand and cardiovascular response during a typical horse riding session.
METHODS: To this aim, 19 (9 male, 10 female) riders, regularly participating in
competitions, were enrolled. They underwent a preliminary, incremental exercise
test on a cycle-ergometer to assess their anaerobic threshold (AT) and VO2max.
Then, participants underwent a riding training session, which comprised periods
of walking, trotting, and cantering for a total of 20 min. Oxygen uptake (VO2),
carbon dioxide production (VCO2), and heart rate (HR) were obtained throughout
the preliminary and riding test by means of a portable metabolic system.
Moreover, excess of CO2 production (CO2excess) and oxygen pulse (OP) were also
calculated to obtain an estimate of anaerobic glycolysis and stroke volume.
RESULTS: The main result was that all collected parameters remained below the AT
level throughout the riding session, with the exception of HR that approached the
AT level only during cantering. In detail, during cantering, average VO2, VCO2,
HR, CO2excess, and OP values were 1289 +/- 331 mL min(-1), 1326 +/- 266 mL min(
1), 158 +/- 22 bpm, 215 +/- 119 mL min(-1), and 7.8 +/- 1.6 mL/bpm, respectively.
CONCLUSIONS: It was concluded that riding imposes only light to moderate stress
on the aerobic and anaerobic energy systems. Moreover, cardiovascular reserve is
only moderately recruited in terms of inotropism, while chronotropism can be
stimulated more.
PMID- 27485470
TI - A process to control light in a micro resonator through a coupling modulation by
surface acoustic waves.
AB - A novel process to control light through the coupling modulation by surface
acoustic wave (SAW) is presented in an optical micro resonator. An optical
waveguide modulator of a racetrack resonator on silicon-on-insulator (SOI)
technology is took as an example to explore the mechanism. A finite-difference
time-domain (FDTD) is developed to simulate the acousto-optical (AO) modulator
using the mechanism. An analytical method is presented to verify our proposal.
The results show that the process can work well as an optical modulator by SAW.
PMID- 27485469
TI - No evidence of neural adaptations following chronic unilateral isometric training
of the intrinsic muscles of the hand: a randomized controlled study.
AB - PURPOSE: To test whether long-term cortical adaptations occur bilaterally
following chronic unilateral training with a simple motor task. METHODS:
Participants (n = 34) were randomly allocated to a training or control groups.
Only the former completed a 4-week maximal-intensity isometric training of the
right first dorsal interosseus muscle through key pinching. Maximal strength was
assessed bilaterally in four different movements progressively less similar to
the training task: key, tip and tripod pinches, and handgrip. Transcranial
magnetic stimulation was used to probe, in the left and right primary hand motor
cortices, a number of standard tests of cortical excitability, including
thresholds, intra-cortical inhibition and facilitation, transcallosal inhibition,
and sensory-motor integration. RESULTS: Training increased strength in the
trained hand, but only for the tasks specifically involving the trained muscle
(key +8.5 %; p < 0.0005; tip +7.2 %; p = 0.02). However, the effect size was
small and below the cutoff for meaningful change. Handgrip and tripod pinch were
instead unaffected. There was a similar improvement in strength in the untrained
hand, i.e., a cross-education effect (key +6.4 %; p = 0.02; tip +4.7 %; p =
0.007). Despite these changes in strength, no significant variation was observed
in any of the neurophysiological parameters describing cortico-spinal and intra
cortical excitability, inter-hemispheric inhibition, and cortical sensory-motor
integration. CONCLUSIONS: A 4-week maximal-intensity unilateral training induced
bilaterally spatial- and task-specific strength gains, which were not associated
to direct or crossed cortical adaptations. The observed long-term stability of
neurophysiological parameters might result from homeostatic plasticity phenomena,
aimed at restoring the physiological inter-hemispheric balance of neural activity
levels perturbed by the exercise. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
identifier NCT02010398.
PMID- 27485471
TI - Abnormal histone acetylation of CD8+ T cells in patients with severe aplastic
anemia.
AB - Severe aplastic anemia (SAA) is a rare autoimmune disease characterized by severe
pancytopenia and bone marrow failure, which is caused by activated T lymphocytes.
In the present study, we evaluated histone H3 acetylation levels of bone marrow
CD8+ T cells in SAA patients, and analyzed its correlation with clinical
condition parameters. We found that the percentages of CD8+ T cell histone H3
acetylation in patients with untreated SAA, recovering SAA (R-SAA) and normal
control, were 1.21 +/- 0.08, 1.05 +/- 0.36, and 1.00 +/- 0.41, respectively, with
no significant statistical differences. However, the amount of CD8+ T cell
histone H3 acetylation from untreated SAA was 176.21 +/- 32.22 MUg/mg protein,
which was significantly higher than that of complete response (CR)-SAA (104.29 +/
62.06 MUg/mg protein) and normal control (133.94 +/- 56.27 MUg/mg protein) (P <
0.05) groups. Moreover, histone H3 acetylation amount of CD8+ T cell was
significantly and negatively correlated with absolute neutrophil count,
proportion of reticulocytes, ratio of CD4+ to CD8+ T cell in peripheral blood,
and percentage of bone marrow erythroid (P < 0.05). To some extent, it also
negatively correlated with hemoglobin level, platelet count, percentage of bone
marrow granulocyte, and megakaryocyte count. Abnormal histone H3 acetylation of
CD8+ T cells may thus play a role in the immune pathogenesis of SAA.
PMID- 27485472
TI - Panobinostat for the treatment of acute myelogenous leukemia.
AB - INTRODUCTION: Therapeutic strategies in patients with acute myeloid leukemia
(AML) have not changed significantly over the last decades. Appropriate
strategies are ultimately driven by the assessment of patients' fitness to define
suitability for intensive induction chemotherapy, which produces high initial
remission rates but, increased likelihood of relapse. Old/unfit AML patients
still represent an urgent and unmet therapeutic need. Epigenetic deregulation
represents a strategic characteristic of AML pathophysiology whereby aberrant
gene transcription provides an advantage to leukemic cell survival. Efforts to re
establish impaired epigenetic regulation include hypomethylating agents and
histone deacetylase inhibitors (HDACi). AREAS COVERED: The review discusses the
underlying mechanisms leading to disruption of lysine acetyltransferases (KAT or
HAT)/deacetylase (KDAC or HDAC) balance and the rationale for using the HDACi
panobinostat (LBH-589) in AML. EXPERT OPINION: Although panobinostat has produced
significant results in myeloma, its efficacy remains limited in AML. Panobinostat
exerts pleiotropic activity and lack of specificity, which likely contributes to
its inadequate safety in elderly AML patients. Phase I-II trials, utilizing
panobinostat associated with well-known chemotherapeutic agents are ongoing and
combinations with other druggable targets may likely be evaluated in future
trials. The clinical use of this HDACi in AML the near future does not appearing
promising.
PMID- 27485473
TI - Jasmonic acid protects etiolated seedlings of Arabidopsis thaliana against
herbivorous arthropods.
AB - Seed predators can cause mass ingestion of larger seed populations. As well,
herbivorous arthropods attempt to attack etiolated seedlings and chose the apical
hook for ingestion, aimed at dropping the cotyledons for later consumption.
Etiolated seedlings, as we show here, have established an efficient mechanism of
protecting their Achilles' heel against these predators, however. Evidence is
provided for a role of jasmonic acid (JA) in this largely uncharacterized plant
herbivore interaction during skotomorphogenesis and that this comprises the
temporally and spatially tightly controlled synthesis of a cysteine protease
inhibitors of the Kunitz family. Interestingly, the same Kunitz protease
inhibitor was found to be expressed in flowers of Arabidopsis where endogenous JA
levels are high for fertility. Because both the apical hook and inflorescences
were preferred isopod targets in JA-deficient plants that could be rescued by
exogenously administered JA, our data identify a JA-dependent mechanism of plant
arthropod deterrence that is recalled in different organs and at quite different
times of plant development.
PMID- 27485474
TI - Tissue-resident Eomes(hi) T-bet(lo) CD56(bright) NK cells with reduced
proinflammatory potential are enriched in the adult human liver.
AB - The adult human liver is enriched with natural killer (NK) cells, accounting for
30-50% of hepatic lymphocytes, which include tissue-resident hepatic NK-cell
subpopulations, distinct from peripheral blood NK cells. In murine liver, a
subset of liver-resident hepatic NK cells have altered expression of the two
highly related T-box transcription factors, T-bet and eomesodermin (Eomes). Here,
we investigate the heterogeneity of T-bet and Eomes expression in NK cells from
healthy adult human liver with a view to identifying human liver-resident
populations. Hepatic NK cells were isolated from donor liver perfusates and
biopsies obtained during orthotopic liver transplantation (N = 28). Hepatic
CD56(bright) NK cells were Eomes(hi) T-bet(lo) , a phenotype virtually absent
from peripheral blood. These NK cells express the chemokine receptor CXCR6
(chemokine (C-X-C motif) receptor 6), a marker of tissue residency, which is
absent from hepatic CD56(dim) and blood NK cells. Compared to blood populations,
these hepatic CD56(bright) NK cells have increased expression of activatory
receptors (NKp44, NKp46, and NKG2D). They show reduced ability to produce IFN
gamma but enhanced degranulation in response to challenge with target cells. This
functionally distinct population of hepatic NK cells constitutes 20-30% of the
total hepatic lymphocyte repertoire and represents a tissue-resident immune cell
population adapted to the tolerogenic liver microenvironment.
PMID- 27485476
TI - The impact of dementia on women internationally: An integrative review.
AB - Women are disproportionately affected by dementia, both in terms of developing
dementia and becoming caregivers. We conducted an integrative review of English
language literature focusing on the issues affecting women in relation to
dementia from an international perspective. The majority of relevant studies were
conducted in high-income countries, and none were from low-income countries. The
effects of caregiving on health, well-being, and finances are greater for women;
issues facing women, particularly in low- and middle-income countries, need to be
better understood. Research should focus on building resilience to help people
adjust and cope long term.
PMID- 27485475
TI - Identifying fusion transcripts using next generation sequencing.
AB - Fusion transcripts (i.e., chimeric RNAs) resulting from gene fusions have been
used successfully for cancer diagnosis, prognosis, and therapeutic applications.
In addition, many fusion transcripts are found in normal human cell lines and
tissues, with some data supporting their role in normal physiology. Besides
chromosomal rearrangement, intergenic splicing can generate them. Global
identification of fusion transcripts becomes possible with the help of next
generation sequencing technology like RNA-Seq. In the past decade, major
advancements have been made for chimeric RNA discovery due to the development of
advanced sequencing platform and software packages. However, current software
tools behave differently in terms of specificity, sensitivity, time, and
computational memory usage. Recent benchmarking studies showed that none of the
tools are inclusive. The development of high performance (accurate and fast), and
user-friendly fusion detection tool/pipeline is still an open quest. In this
article, we review the existing software packages for fusion detection. We
explain the methods of the tools, and discuss various factors that affect fusion
detection. We summarize conclusions drawn from several comparative studies, and
then discuss some of the pitfalls of these studies. We also describe the
limitations of current tools, and suggest directions for future development.
WIREs RNA 2016, 7:811-823. doi: 10.1002/wrna.1382 For further resources related
to this article, please visit the WIREs website.
PMID- 27485477
TI - Clinical risk factors associated with the post-transplant anemia in kidney
transplant patients.
AB - BACKGROUND: Anemia is a very common occurrence in post-renal transplant patients.
Post-transplantation anemia (PTA) is associated with significant graft loss or
cardiovascular morbidity. The objective of this study is to identify clinical
risk factors associated with anemia after kidney transplantation. METHODS: Our
retrospective cohort study included a total of 570 renal transplant recipients.
For the definition of anemia, we adopted "the lower limit of normal for Hgb
concentration of blood" proposed by Beutler E and Waalen J [14], which has
adjustments for age, gender and ethnicity. Post-transplant anemia (PTA) was
defined as anemia that arose between 30 and 180days after transplantation. Based
on this definition, of the 570 renal transplant recipients, 344 patients (62.1%)
experienced PTA. The patients were divided into anemic and non-anemic groups, and
a total of 20 clinical factors were compared between the two groups. RESULTS: In
the univariate analysis, age, race, multiple transplants, delayed graft function
(DGF), and use of tacrolimus, sirolimus, thymoglobulin, ganciclovir, ACE
inhibitors, and ARBs were associated with PTA. In the multivariate analysis, age
(>60years old, OR=2.62, p=0.001), race (OR=2.54, p=0.001), and use of sirolimus
(OR=2.01, p=0.019), antiviral agents (OR=1.96, p=0.015), thymoglobulin (OR=1.86,
p=0.011), and DGF (OR=2.78, p=0.001) remained significant. CONCLUSION: The
current results show that undergoing a transplant at age 60 or older, use of
sirolimus, antiviral agents, and thymoglobulin are independent clinical risk
factors associated with PTA. In terms of ethnicity, AA, MEA, or PI is higher risk
for PTA and Hispanic is significantly lower risk for PTA compared to Caucasians.
PMID- 27485478
TI - Multistimuli-Responsive Bilirubin Nanoparticles for Anticancer Therapy.
AB - Although stimuli-responsive materials hold potential for use as drug-delivery
carriers for treating cancers, their clinical translation has been limited.
Ideally, materials used for the purpose should be biocompatible and nontoxic,
provide "on-demand" drug release in response to internal or external stimuli,
allow large-scale manufacturing, and exhibit intrinsic anticancer efficacy. We
present multistimuli-responsive nanoparticles formed from bilirubin, a potent
endogenous antioxidant that possesses intrinsic anticancer and anti-inflammatory
activity. Exposure of the bilirubin nanoparticles (BRNPs) to either reactive
oxygen species (ROS) or external laser light causes rapid disruption of the BRNP
nanostructure as a result of a switch in bilirubin solubility, thereby releasing
encapsulated drugs. In a xenograft tumor model, BRNPs loaded with the anticancer
drug doxorubicin (DOX@BRNPs), when combined with laser irradiation of 650 nm,
significantly inhibited tumor growth. This study suggests that BRNPs may be used
as a drug-delivery carrier as well as a companion medicine for effectively
treating cancers.
PMID- 27485479
TI - In vivo strain in the deep and superficial regions of the human patellar tendon.
AB - This study investigated strain differences within the patellar tendon (PT) mid
region using an ultrasound-based digital image correlation (DIC) method. Six
healthy young participants performed six knee extensions to 60% of maximal
voluntary isometric contraction on 2 days. Sagittal ultrasound videos recorded
during each contraction were analyzed using the DIC method to determine the
strain-torque relationships of the superficial, deep, and whole PT mid-regions.
Significantly greater strain was observed in the deep vs superficial layer of the
PT mid-region for all contraction intensities, with peak strains of 5.8% (SD 1.7)
and 4.5% (SD 1.5), respectively. DIC-based measures of peak tendon strain were
repeatable within [intraclass coefficients (ICC) >0.97] and between sessions
(ICCs >0.83) and agreed well with the conventional point-to-point method. This
study confirmed that significant differences exist between deep and superficial
layers of PT mid-region during ramped isometric extensions. These findings
support the use of DIC to examine regional strain patterns within the PT mid
region that may be important in the context of tendon injury and adaptation.
PMID- 27485480
TI - Seminal fluid and fertility in women.
AB - Seminal fluid is often viewed as simply a vehicle to carry sperm to fertilize the
oocyte, but a more complex function in influencing female reproductive physiology
is now evident. Remarkably, seminal fluid contains soluble and exosome-born
signaling agents that interact with the female reproductive tract to prime the
immune response, with consequences for fertility and pregnancy outcome.
Experiments in rodent models demonstrate a key role for seminal fluid in enabling
robust embryo implantation and optimal placental development. In particular,
seminal fluid promotes leukocyte recruitment and generation of regulatory T
cells, which facilitate embryo implantation by suppressing inflammation,
assisting uterine vascular adaptation, and sustaining tolerance of fetal
antigens. There is emerging evidence of comparable effects in women, where
seminal fluid provokes an adaptive immune response in the cervical tissues after
contact at intercourse, and spermatozoa accessing the higher tract potentially
affect the endometrium directly. These biological responses may have clinical
significance, explaining why [1] intercourse in IVF ET cycles improves the
likelihood of pregnancy, [2] inflammatory disorders of gestation are more common
in women who conceive after limited exposure to seminal fluid of the prospective
father, and [3] preeclampsia incidence is elevated after use of donor oocytes or
donor sperm where prior contact with conceptus alloantigens has not occurred. It
will be important to define the mechanisms through which seminal fluid interacts
with female reproductive tissues, to provide knowledge that may assist in
preconception planning and infertility treatment.
PMID- 27485481
TI - Synthesis and evaluation of an (18)F-labeled pyrimidine-pyridine amine for
targeting CXCR4 receptors in gliomas.
AB - INTRODUCTION: Chemokine receptor-4 (CXCR4, fusin, CD184) is expressed on several
tissues involved in immune regulation and is upregulated in many diseases
including malignant gliomas. A radiolabeled small molecule that readily crosses
the blood-brain barrier can aid in identifying CXCR4-expressing gliomas and
monitoring CXCR4-targeted therapy. In the current work, we have synthesized and
evaluated an [(18)F]-labeled small molecule based on a pyrimidine-pyridine amine
for its ability to target CXCR4. EXPERIMENTAL: The nonradioactive standards and
the nitro precursor used in this study were prepared using established methods.
An HPLC method was developed to separate the nitro-precursor from the
nonradioactive standard and radioactive product. The nitro-precursor was
radiolabeled with (18)F under inert, anhydrous conditions using the [(18)F]
kryptofix 2.2.2 complex to form the desired N-(4-(((6-[(18)F]fluoropyridin-2
yl)amino)methyl)benzyl)pyrimidin-2-amine ([(18)F]-3). The purified radiolabeled
compound was used in serum stability, partition coefficient, cellular uptake, and
in vivo cancer targeting studies. RESULTS: [(18)F]-3 was synthesized in 4-10%
decay-corrected yield (to start of synthesis). [(18)F]-3 (tR ~ 27 min) was
separated from the precursor (tR ~ 30 min) using a pentafluorophenyl column with
an isocratic solvent system. [(18)F]-3 displayed acceptable serum stability over
2 h. The amount of [(18)F]-3 bound to the plasma proteins was determined to be >
97%. The partition coefficient (LogD7.4) is 1.4 +/- 0.5. Competitive in vitro
inhibition indicated 3 does not inhibit uptake of (67)Ga-pentixafor. Cell culture
media incubation and ex vivo urine analysis indicate rapid metabolism of [(18)F]
3 into hydrophilic metabolites. Thus, in vitro uptake of [(18)F]-3 in CXCR4
overexpressing U87 cells (U87 CXCR4) and U87 WT indicated no specific binding. In
vivo studies in mice bearing U87 CXCR4 and U87 WT tumors on the left and right
shoulders were carried out using [(18)F]-3 and (68)Ga-pentixafor on consecutive
days. The CXCR4 positive tumor was clearly visualized in the PET study using
(68)Ga-pentixafor, but not with [(18)F]-3. CONCLUSIONS: We have successfully
synthesized both a radiolabeled analog to previously reported CXCR4-targeting
molecules and a nitro precursor. Our in vitro and in vivo studies indicate that
[(18)F]-3 is rapidly metabolized and, therefore, does not target CXCR4-expressing
tumors. Optimization of the structure to improve the in vivo (and in vitro)
stability, binding, and solubility could lead to an appropriate CXCR4-targeted
radiodiagnositic molecule.
PMID- 27485482
TI - Incidence of advanced neoplasia during surveillance in high- and intermediate
risk groups of the European colorectal cancer screening guidelines.
AB - Background and study aims: The European guidelines for quality assurance in
colorectal cancer (CRC) screening have established high-risk (>= 5 adenomas or an
adenoma >= 20 mm) and intermediate-risk (3 - 4 adenomas or at least one adenoma
10 - 19 mm in size, or villous histology, or high grade dysplasia) groups with
different endoscopic surveillance intervals. The aim of this study was to
evaluate the difference in the incidence of advanced neoplasia (advanced adenoma
or CRC) between the two risk groups. Patients and methods: This retrospective
group study included patients meeting high- or intermediate-risk criteria for
adenomas detected in CRC screening programs and the COLONPREV study before
European guidelines were adopted in Spain (June 2011) with a 3-year surveillance
recommendation according to Spanish guidelines. The primary outcome measure was
the incidence of advanced neoplasia in patients undergoing surveillance. The
secondary outcome measure was the CRC incidence. We used an adjusted proportional
hazards regression model to control confounding variables. Results: The study
included 5401 patients (3379 intermediate risk, 2022 high risk). Endoscopic
surveillance was performed in 65.5 % of the patients (2.8 +/- 1 years). The
incidence of advanced neoplasia in the high- and intermediate-risk groups was
16.0 % (59.0 cases/1000 patient-years) and 12.3 % (41.2 cases/1000 patient
years), respectively. The CRC incidence was 0.5 % (1.4 cases/1000 patient-years)
and 0.4 % (1 case/1000 patient-years), respectively. The advanced neoplasia and
CRC attributable risk to the high risk group was of 3.7 % and 0.1 %,
respectively. In the proportional hazards analysis, the risk of advanced
neoplasia was greater in the high-risk group (hazard ratio [HR] 1.5, 95 %
confidence interval [CI] 1.2 - 1.8), with no significant differences in the CRC
incidence (HR 1.6, 95 %CI 0.6 - 3.8). Conclusions: Patients meeting high-risk
criteria have a higher incidence of advanced neoplasia during endoscopic
surveillance. No differences were found in the CRC incidence at a 3-year
surveillance recommendation.
PMID- 27485483
TI - European Society of Gastrointestinal Endoscopy - Establishing the key unanswered
research questions within gastrointestinal endoscopy.
AB - Background and study aim: Gastrointestinal endoscopy is a rapidly evolving
research field. The European Society of Gastrointestinal Endoscopy (ESGE) plays a
key role in shaping opinion and endoscopy activity throughout Europe and further
afield. Establishing key unanswered questions within the field of endoscopy and
prioritizing those that are important enables researchers and funders to
appropriately allocate resources. Methods: Over 2 years, the ESGE Research
Committee gathered information on research priorities and refined them through a
modified Delphi approach. Consultations were held with the ESGE Governing Board
and Quality Improvement Committee to identify important unanswered questions.
Research workshops were held at the 21st United European Gastroenterology Week.
Research questions were refined by the ESGE Research Committee and Governing
Board, compiled into an online survey, and distributed to all ESGE members, who
were invited to rank each question by priority. Results: The final questionnaire
yielded 291 responses from over 60 countries. The three countries with the
highest response rates were Spain, Italy, and United Kingdom. Most responders
were from teaching hospitals (62 %) and were specialist endoscopists (51 %).
Responses were analyzed with weighted rankings, resulting in prioritization of 26
key unanswered questions. The top ranked generic questions were: 1) How do we
define the correct surveillance interval following endoscopic diagnosis? 2) How
do we correctly utilize advanced endoscopic imaging? 3) What are the best markers
of endoscopy quality? Conclusion: Following this comprehensive process, the ESGE
has identified and ranked the key unanswered questions within the field of
gastrointestinal endoscopy. Researchers, funders, and journals should prioritize
studies that seek to answer these important questions.
PMID- 27485484
TI - hiPSC-derived cardiomyocytes from Brugada Syndrome patients without identified
mutations do not exhibit clear cellular electrophysiological abnormalities.
AB - Brugada syndrome (BrS) is a rare cardiac rhythm disorder associated with sudden
cardiac death. Mutations in the sodium channel gene SCN5A are found in ~20% of
cases while mutations in other genes collectively account for <5%. In the
remaining patients the genetic defect and the underlying pathogenic mechanism
remain obscure. To provide insight into the mechanism of BrS in individuals
without identified mutations, we here studied electrophysiological properties of
cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs)
from 3 BrS patients who tested negative for mutations in the known BrS-associated
genes. Patch clamp studies revealed no differences in sodium current (INa) in
hiPSC-CMs from the 3 BrS patients compared to 2 unrelated controls. Moreover,
action potential upstroke velocity (Vmax), reflecting INa, was not different
between hiPSC-CMs from the BrS patients and the controls. hiPSC-CMs harboring the
BrS-associated SCN5A-1795insD mutation exhibited a reduction in both INa and
Vmax, demonstrating our ability to detect reduced sodium channel function. hiPSC
CMs from one of the BrS lines demonstrated a mildly reduced action potential
duration, however, the transient outward potassium current (Ito) and the L-type
calcium current (ICa,L), both implicated in BrS, were not different compared to
the controls. Our findings indicate that ion channel dysfunction, in particular
in the cardiac sodium channel, may not be a prerequisite for BrS.
PMID- 27485485
TI - Umbilical cord-derived mesenchymal stem cells inhibit growth and promote
apoptosis of HepG2 cells.
AB - Hepatocellular carcinoma is the fifth most common type of cancer worldwide and
remains difficult to treat. The aim of this study was to investigate the effects
of mesenchymal stem cells (MSCs) derived from the umbilical cord (UC-MSCs) on
HepG2 hepatocellular carcinoma cells. UC-MSCs were co-cultured with HepG2 cells
and biomarkers of UC-MSCs were analyzed by flow cytometry. mRNA and protein
expression of genes were determined by reverse transcription-polymerase chain
reaction and flow cytometry, respectively. Passage three and seven UC-MSCs
expressed CD29, CD44, CD90 and CD105, whereas CD34 and CD45 were absent on these
cells. Co-culture with UC-MSCs inhibited proliferation and promoted apoptosis of
HepG2 cells in a time-dependent manner. The initial seeding density of UC-MSCs
also influenced the proliferation and apoptosis of HepG2 cells, with an increased
number of UC-MSCs causing enhanced proliferation inhibition and cell apoptosis.
Co-culture with UC-MSCs downregulated mRNA and protein expression of alpha
fetoprotein (AFP), Bcl-2 and Survivin in HepG2 cells. Thus, UC-MSCs may inhibit
growth and promote apoptosis of HepG2 cells through downregulation of AFP, Bcl-2
and Survivin. US-MSCs may be used as a novel therapy for treating hepatocellular
carcinoma in the future.
PMID- 27485486
TI - Capacity to improve fine motor skills in Williams syndrome.
AB - BACKGROUND: Individuals with Williams syndrome (WS) are known to have
difficulties in carrying out fine motor movements; however, a detailed
behavioural profile of WS in this domain is still missing. It is also unknown how
great the capacity to improve these skills with focused and extensive practice
is. METHOD: We studied initial performance and learning capacity in a sequential
finger tapping (FT) task in WS and in typical development. Improvement in the FT
task has been shown to be sleep dependent. WS subjects participating in the
current study have also participated in earlier polysomnography studies, although
not directly related to learning. RESULTS: WS participants presented with great
individual variability. In addition to generally poor initial performance,
learning capacity was also greatly limited in WS. We found indications that
reduced sleep efficiency might contribute to this limitation. CONCLUSIONS:
Estimating motor learning capacity and the depth of sleep disorder in a larger
sample of WS individuals might reveal important relationships between sleep and
learning, and contribute to efficient intervention methods improving skill
acquisition in WS.
PMID- 27485487
TI - Spatiotemporal characteristics of the pharyngeal event-related potential in
healthy subjects and older patients with oropharyngeal dysfunction.
AB - BACKGROUND: Oropharyngeal dysphagia (OD) is a highly prevalent symptom in older
people. Appropriate oropharyngeal sensory feedback is essential for safe and
efficient swallowing. However, pharyngeal sensitivity decreases with advancing
age and could play a fundamental role in the physiopathology of swallowing
dysfunction associated with aging. We aimed to characterize pharyngeal
sensitivity and cortical response to a pharyngeal electrical stimulus in healthy
volunteers (HV) and older patients with and without OD. METHODS: Eight young HV,
eight older HV without OD, and 14 older patients with OD were studied by
electroencephalography through 32 scalp electrodes. Pharyngeal event-related
potentials (ERP) were assessed following electrical stimulation of the pharynx.
Sensory and tolerance thresholds to the electrical stimulus and latency,
amplitude, and scalp current density of each ERP component were analyzed and
compared. An ERP source localization study was also performed using the sLORETA
software. KEY RESULTS: Older participants (with and without OD) presented an
increased sensory threshold to pharyngeal electrical stimulation (10.2 +/- 1.7 mA
and 11.5 +/- 1.9 mA respectively), compared with young HV (6.0 +/- 1.2 mA). The
cortical activation of older HV in response to pharyngeal electrical stimulus was
reduced compared with young HV (N2 amplitude: 0.22 +/- 0.79 vs -3.10 +/- 0.59,
P<.05). Older patients with OD also presented disturbances to the pharyngo
cortical connection together with disrupted pattern of cortical activation.
CONCLUSIONS AND INFERENCES: Older people present a decline in pharyngeal sensory
function, more severe in older patients with OD. This sensory impairment might be
a critical pathophysiological element and a potential target for treatment of
swallowing dysfunction in older patients.
PMID- 27485488
TI - The differential effects of alprazolam and oxazepam on methamphetamine self
administration in rats.
AB - BACKGROUND: Methamphetamine is the second most commonly used illicit drug in the
world, and despite recent attempts by the Drug Enforcement Administration to
combat this epidemic, methamphetamine use is still on the rise. As
methamphetamine use increases so does polydrug use, particularly that involving
methamphetamine and benzodiazepines. The present study was designed to examine
the effects of two benzodiazepines on methamphetamine self-administration.
METHODS: Five doses of methamphetamine (0.0075, 0.015, 0.03, 0.09, and
0.12mg/kg/infusion) were tested, producing an inverted U-shaped dose-response
curve. Rats were then pretreated with oxazepam, alprazolam, or vehicle prior to
methamphetamine self-administration. To determine if the effects of these drugs
were due to the GABAA receptor and/or translocator protein (TSPO), we also
pretreated rats with an antagonist for the benzodiazepine-binding site on the
GABAA receptor (i.e., flumazenil) and a TSPO antagonist (i.e., PK11195) prior to
alprazolam or oxazepam administration. RESULTS: Oxazepam significantly reduced
methamphetamine self-administration as demonstrated by a downward shift of the
dose-response curve. In contrast, alprazolam significantly enhanced
methamphetamine self-administration as evidenced by a leftward shift of the dose
response curve. Flumazenil completely blocked the effects of alprazolam on
methamphetamine self-administration. When administered individually, both
flumazenil and PK11195 partially reversed the effects of oxazepam on
methamphetamine self-administration. However, when these two antagonists were
combined, the effects of oxazepam were completely reversed. CONCLUSIONS: The
GABAA receptor is responsible for the alprazolam-induced enhancement of
methamphetamine self-administration, while the activation of both the GABAA
receptor and TSPO are responsible for the oxazepam-induced reduction of
methamphetamine self-administration.
PMID- 27485489
TI - Structural characterization, molecular modification and hepatoprotective effect
of melanin from Lachnum YM226 on acute alcohol-induced liver injury in mice.
AB - In this paper, the possible structural formula of the intracellular homogeneous
melanin of Lachnum YM226 (LM) was concluded based on an elemental assay,
ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared
spectroscopy (FTIR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and
equivalent series resistance (ESR). Meanwhile, a d-glucosamine melanin derivative
(GLM) was also prepared and its cytotoxicity was evaluated using the MTT assay.
The hepatoprotective effect of LM and GLM was evaluated in an acute alcohol
induced liver injury model. The results showed that pretreatments with LM and GLM
markedly decreased subsequent alcohol elicited acute hepatic oxidative and
inflammatory stress via improving the activity of antioxidant enzymes
(glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), and total
superoxide dismutase (SOD)), reducing hepatic levels of nuclear transcription
factor (NF-kappaB), cytokines related to its activation (interleukin (IL)-6,
tumor necrosis factor (TNF)-alpha and macrophage chemoattractant protein (MCP)-1)
and hepatic activities of inducible nitric oxide synthase (iNOS) and
cyclooxygenase (COX)-2. The protection properties of alcoholic liver injury of
GLM were more obvious than that of LM at the same dose. The present findings
recommend that LM and GLM may be used as a prototype for the prevention of
alcoholic liver injury.
PMID- 27485490
TI - Comparing Weight-for-Length Status of Young Children in Two Infant Feeding
Programs.
AB - Objectives A cross-sectional study comparing weight-for-length status of children
6-24 months old who participated in Nurse-Family Partnership (NFP) or Special
Supplemental Program for Women, Infants, and Children (WIC). Methods Secondary
analysis of NFP (n = 44,980) and WIC (n = 31,294) national datasets was conducted
to evaluate infant and toddler growth trajectories. Weight-for-length status was
calculated at 6, 12, 18, and 24 months based on World Health Organization
criteria. Demographics and breastfeeding rates were also evaluated. Binary
logistic regression was used to calculate odds ratios for high weight-for-length
(>=97.7 percentile) at each time point. Results At 6 months, approximately 10 %
of WIC and NFP children were classified as high weight-for-length. High weight
for-length rates increased for both groups similarly until 24 months. At 24
months, NFP children had significantly lower rates of excess weight (P = 0.03)
than WIC children, 15.5 and 17.5 % respectively. At all time points, non-Hispanic
white children had lower rates of high-weight for length than Hispanic and non
Hispanic black children. NFP infants were also found to have higher rates of ever
being breastfed than WIC infants (P < 0.0001). Conclusions for Practice Infant
and toddler populations served by NFP or WIC were found to be at increased risk
for high weight-for-length. This study found NFP participation was associated
with a small, but significant, protective impact on weight-for-length status at
24 months. Continued efforts need to be made in addressing weight-related
racial/ethnic and socioeconomic disparities during early childhood.
PMID- 27485492
TI - Hurricane Charley Exposure and Hazard of Preterm Delivery, Florida 2004.
AB - Objective Hurricanes are powerful tropical storm systems with high winds which
influence many health effects. Few studies have examined whether hurricane
exposure is associated with preterm delivery. We aimed to estimate associations
between maternal hurricane exposure and hazard of preterm delivery. Methods We
used data on 342,942 singleton births from Florida Vital Statistics Records 2004
2005 to capture pregnancies at risk of delivery during the 2004 hurricane season.
Maternal exposure to Hurricane Charley was assigned based on maximum wind speed
in maternal county of residence. We estimated hazards of overall preterm delivery
(<37 gestational weeks) and extremely preterm delivery (<32 gestational weeks) in
Cox regression models, adjusting for maternal/pregnancy characteristics. To
evaluate heterogeneity among racial/ethnic subgroups, we performed analyses
stratified by race/ethnicity. Additional models investigated whether exposure to
multiples hurricanes increased hazard relative to exposure to one hurricane.
Results Exposure to wind speeds >=39 mph from Hurricane Charley was associated
with a 9 % (95 % CI 3, 16 %) increase in hazard of extremely preterm delivery,
while exposure to wind speed >=74 mph was associated with a 21 % (95 % CI 6, 38
%) increase. Associations appeared greater for Hispanic mothers compared to non
Hispanic white mothers. Hurricane exposure did not appear to be associated with
hazard of overall preterm delivery. Exposure to multiple hurricanes did not
appear more harmful than exposure to a single hurricane. Conclusions Hurricane
exposure may increase hazard of extremely preterm delivery. As US coastal
populations and hurricane severity increase, the associations between hurricane
and preterm delivery should be further studied.
PMID- 27485491
TI - The Impact of Perinatal Depression on Children's Social-Emotional Development: A
Longitudinal Study.
AB - Objectives This longitudinal population study aimed to investigate if maternal
depression at different time points during the perinatal period impacts
children's social-emotional development at 2 years of age. Methods Participants
were women (n = 1235) who gave birth at Akershus University Hospital in Norway.
Maternal depressive symptoms were assessed by using the Edinburgh Postnatal
Depression Scale at pregnancy week 32 and at 8 weeks and 2 years postpartum,
whereas children's social-emotional development at the age of 2 years was
assessed by using the Ages and Stages Questionnaire: Social-Emotional. Bi- and
multivariate logistic regression analyses were conducted to examine the linkage
between maternal perinatal depression and children's early social-emotional
development. Results Multivariate analyses showed that social-emotional problems
in the child 2 years after birth were strongly associated with maternal
depression at pregnancy week 32 (adjusted odds ratio (aOR) 3.4; 95 % CI 1.4-8.0),
depression at 8 weeks postpartum (aOR 3.8; 95 % CI 1.7-8.6), and with depression
at both time points (aOR 3.7; 95 % CI 1.5-10.1). Conclusion Findings indicate pre
and postnatal depression each bears an independent, adverse impact on children's
social-emotional development.
PMID- 27485493
TI - Group Prenatal Care Attendance: Determinants and Relationship with Care
Satisfaction.
AB - Objectives Group prenatal care results in improved birth outcomes in randomized
controlled trials, and better attendance at group prenatal care visits is
associated with stronger clinical effects. This paper's objectives are to
identify determinants of group prenatal care attendance, and to examine the
association between proportion of prenatal care received in a group context and
satisfaction with care. Methods We conducted a secondary data analysis of
pregnant adolescents (n = 547) receiving group prenatal care in New York City
(2008-2012). Multivariable linear regression models were used to test
associations between patient characteristics and percent of group care sessions
attended, and between the proportion of prenatal care visits that occurred in a
group context and care satisfaction. Results Sixty-seven groups were established.
Group sizes ranged from 3 to 15 women (mean = 8.16, SD = 3.08); 87 % of groups
enrolled at least five women. Women enrolled in group prenatal care supplemented
group sessions with individual care visits. However, the percent of women who
attended each group session was relatively consistent, ranging from 56 to 63 %.
Being born outside of the United States was significantly associated with higher
group session attendance rates [B(SE) = 11.46 (3.46), p = 0.001], and women who
received a higher proportion of care in groups reported higher levels of care
satisfaction [B(SE) = 0.11 (0.02), p < 0.001]. Conclusions Future research should
explore alternative implementation structures to improve pregnant women's ability
to receive as much prenatal care as possible in a group setting, as well as value
based reimbursement models and other incentives to encourage more widespread
adoption of group prenatal care.
PMID- 27485494
TI - Effect of Modifiable Risk Factors on Preterm Birth: A Population Based-Cohort.
AB - Objectives The purpose of this study is to evaluate the prevalence, impact, and
interaction of short interpregnancy interval (IPI), pre-pregnancy body mass index
(BMI) category, and pregnancy weight gain (PWG) on the rate of preterm birth.
Methods This is a population-based retrospective cohort study using vital
statistics birth records from 2006 to 2011 in OH, US, analyzing singleton live
births to multiparous mothers with recorded IPI (n = 393,441). Preterm birth rate
at <37 weeks gestational age was compared between the referent pregnancy (defined
as normal pre-pregnancy maternal BMI, IPI of 12-24 months, and Institute of
Medicine (IOM) recommended PWG) and those with short or long IPI, abnormal BMI
(underweight, overweight, and obese), and high or low PWG (under or exceeding IOM
recommendations). Results Only 6 % of the women in this study had a referent
pregnancy, with a preterm birth rate of 7.6 % for this group. Short IPIs of <6
and 6-12 months were associated with increased rates of preterm birth rate to
12.9 and 10.4 %, respectively. Low PWG compared to IOM recommendations for pre
pregnancy BMI class was also associated with increased preterm birth rate of 13.2
% for all BMI classes combined. However, the highest rate of preterm birth of
25.2 % occurred in underweight women with short IPI and inadequate weight gain
with adjOR 3.44 (95 % CI 2.80, 4.23). The fraction of preterm births observed in
this cohort that can be attributed to short IPIs is 5.9 %, long IPIs is 8.3 %,
inadequate PWG is 7.5 %, and low pre-pregnancy BMI is 2.2 %. Conclusions Our
analysis indicates that a significant proportion of preterm births in Ohio are
associated with potentially modifiable risk factors. These data suggest public
health initiatives focused on preterm birth prevention could include counseling
and interventions to optimize preconception health and prenatal nutrition.
PMID- 27485495
TI - Sustained live poultry market surveillance contributes to early warnings for
human infection with avian influenza viruses.
AB - Sporadic human infections with the highly pathogenic avian influenza (HPAI) A
(H5N6) virus have been reported in different provinces in China since April 2014.
From June 2015 to January 2016, routine live poultry market (LPM) surveillance
was conducted in Shenzhen, Guangdong Province. H5N6 viruses were not detected
until November 2015. The H5N6 virus-positive rate increased markedly beginning in
December 2015, and viruses were detected in LPMs in all districts of the city.
Coincidently, two human cases with histories of poultry exposure developed
symptoms and were diagnosed as H5N6-positive in Shenzhen during late December
2015 and early January 2016. Similar viruses were identified in environmental
samples collected in the LPMs and the patients. In contrast to previously
reported H5N6 viruses, viruses with six internal genes derived from the H9N2 or
H7N9 viruses were detected in the present study. The increased H5N6 virus
positive rate in the LPMs and the subsequent human infections demonstrated that
sustained LPM surveillance for avian influenza viruses provides an early warning
for human infections. Interventions, such as LPM closures, should be immediately
implemented to reduce the risk of human infection with the H5N6 virus when the
virus is widely detected during LPM surveillance.
PMID- 27485496
TI - Prevalence of influenza A virus in live-captured North Atlantic gray seals: a
possible wild reservoir.
AB - Influenza A virus (IAV) has been associated with multiple unusual mortality
events (UMEs) in North Atlantic pinnipeds, frequently attributed to spillover of
virus from wild-bird reservoirs. To determine if endemic infection persists
outside of UMEs, we undertook a multiyear investigation of IAV in healthy, live
captured Northwest Atlantic gray seals (Halichoerus grypus). From 2013 to 2015,
we sampled 345 pups and 57 adults from Cape Cod, MA, USA and Nova Scotia, Canada
consistently detecting IAV infection across all groups. There was an overall
viral prevalence of 9.0% (95% confidence interval (CI): 6.4%-12.5%) in weaned
pups and 5.3% (CI: 1.2%-14.6%) in adults, with seroprevalences of 19.3% (CI:
15.0%-24.5%) and 50% (CI: 33.7%-66.4%), respectively. Positive sera showed a
broad reactivity to diverse influenza subtypes. IAV status did not correlate with
measures of animal health nor impact animal movement or foraging. This study
demonstrated that Northwest Atlantic gray seals are both permissive to and
tolerant of diverse IAV, possibly representing an endemically infected wild
reservoir population.
PMID- 27485497
TI - A combination of the QuantiFERON-TB Gold In-Tube assay and the detection of
adenosine deaminase improves the diagnosis of tuberculous pleural effusion.
AB - The differential diagnosis of tuberculous pleural effusion (TPE) and malignant
pleural effusion (MPE) remains difficult despite the availability of numerous
diagnostic tools. The current study aimed to evaluate the performance of the
whole blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and conventional
laboratory biomarkers in differential diagnosis of TPE and MPE in high
tuberculosis prevalence areas. A total of 117 patients with pleural effusions
were recruited, including 91 with TPE and 26 with MPE. All of the patients were
tested with QFT-GIT, and the conventional biomarkers in both blood and pleural
effusion were detected. The level of antigen-stimulated QFT-GIT in the whole
blood of TPE patients was significantly higher than that of MPE (2.89 vs 0.33
IU/mL, P<0.0001). The sensitivity and specificity of QFT-GIT for the diagnosis of
TPE were 93.0% and 60.0%, respectively. Among the biomarkers in blood and pleural
effusion, pleural adenosine deaminase (ADA) was the most prominent biomarker,
with a cutoff value of 15.35 IU/L. The sensitivity and specificity for the
diagnosis of TPE were 93.4% and 96.2%, respectively. The diagnostic
classification tree from the combination of these two biomarkers was 97.8%
sensitive and 92.3% specific. Ultimately, the combination of whole blood QFT-GIT
with pleural ADA improved both the specificity and positive predictive value to
100%. Thus, QFT-GIT is not superior to pleural ADA in the differential diagnosis
of TPE and MPE. Combined whole blood QFT-GIT and pleural ADA detection can
improve the diagnosis of TPE.
PMID- 27485499
TI - Testing for carryover effects after cessation of treatments: a design approach.
AB - BACKGROUND: Recently, trials addressing noisy measurements with diagnosis
occurring by exceeding thresholds (such as diabetes and hypertension) have been
published which attempt to measure carryover - the impact that treatment has on
an outcome after cessation. The design of these trials has been criticised and
simulations have been conducted which suggest that the parallel-designs used are
not adequate to test this hypothesis; two solutions are that either a differing
parallel-design or a cross-over design could allow for diagnosis of carryover.
METHODS: We undertook a systematic simulation study to determine the ability of a
cross-over or a parallel-group trial design to detect carryover effects on
incident hypertension in a population with prehypertension. We simulated blood
pressure and focused on varying criteria to diagnose systolic hypertension.
RESULTS: Using the difference in cumulative incidence hypertension to analyse
parallel-group or cross-over trials resulted in none of the designs having
acceptable Type I error rate. Under the null hypothesis of no carryover the
difference is well above the nominal 5 % error rate. CONCLUSIONS: When a
treatment is effective during the intervention period, reliable testing for a
carryover effect is difficult. Neither parallel-group nor cross-over designs
using the difference in cumulative incidence appear to be a feasible approach.
Future trials should ensure their design and analysis is validated by simulation.
PMID- 27485498
TI - flrA, flrB and flrC regulate adhesion by controlling the expression of critical
virulence genes in Vibrio alginolyticus.
AB - Adhesion is an important virulence trait of Vibrio alginolyticus. Bacterial
adhesion is influenced by environmental conditions; however, the molecular
mechanism underlying this effect remains unknown. The expression levels of flrA,
flrB and flrC were significantly downregulated in adhesion-deficient V.
alginolyticus strains cultured under Cu(2+), Pb(2+), Hg(2+) and low-pH stresses.
Silencing these genes led to deficiencies in adhesion, motility, flagellar
assembly, biofilm formation and exopolysaccharide (EPS) production. The
expression levels of fliA, flgH, fliS, fliD, cheR, cheV and V12G01_22158 (Gene
ID) were significantly downregulated in all of the RNAi groups, whereas the
expression levels of toxT, ctxB, acfA, hlyA and tlh were upregulated in flrA- and
flrC-silenced groups. These genes play a key role in the virulence mechanisms of
most pathogenic Vibrio species. Furthermore, the expression of flrA, flrB and
flrC was significantly influenced by temperature, salinity, starvation and pH.
These results indicate that (1) flrA, flrB and flrC are important for V.
alginolyticus adhesion; (2) flrA, flrB and flrC significantly influence bacterial
adhesion, motility, biofilm formation and EPS production by controlling
expression of key genes involved in those phenotypes; and (3) flrA, flrB and flrC
regulate adhesion in the natural environment with different temperatures, pH
levels, salinities and starvation time.
PMID- 27485500
TI - Congenital primary adrenal insufficiency and selective aldosterone defects
presenting as salt-wasting in infancy: a single center 10-year experience.
AB - BACKGROUND: Salt-wasting represents a relatively common cause of emergency
admission in infants and may result in life-threatening complications. Neonatal
kidneys show low glomerular filtration rate and immaturity of the distal nephron
leading to reduced ability to concentrate urine. METHODS: A retrospective chart
review was conducted for infants hospitalized in a single Institution from 1(st)
January 2006 to 31(st) December 2015. The selection criterion was represented by
the referral to the Endocrinology Unit for hyponatremia (serum sodium <130 mEq/L)
of suspected endocrine origin at admission. RESULTS: Fifty-one infants were
identified. In nine infants (17.6 %) hyponatremia was related to unrecognized
chronic gastrointestinal or renal salt losses or reduced sodium intake. In 10
infants (19.6 %) hyponatremia was related to central nervous system diseases. In
19 patients (37.3 %) the final diagnosis was congenital adrenal hyperplasia
(CAH). CAH was related to 21-hydroxylase deficiency in 18 patients, and to 3beta
Hydroxysteroid dehydrogenase (3betaHSD) deficiency in one patient. Thirteen
patients (25.5 %) were affected by different non-CAH salt-wasting forms of
adrenal origin. Four familial cases of X-linked adrenal hypoplasia congenita due
to NROB1 gene mutation were identified. Two unrelated girls showed aldosterone
synthase deficiency due to mutation of the CYP11B2 gene. Two unrelated infants
were affected by familial glucocorticoid deficiency due to MC2R gene mutations.
One girl showed pseudohypoaldosteronism related to mutations of the SCNN1G gene
encoding for the epithelial sodium channel. Transient pseudohypoaldosteronism was
identified in two patients with renal malformations. In two infants the genetic
aetiology was not identified. CONCLUSIONS: Emergency management of infants
presenting with salt wasting requires correction of water losses and treatment of
electrolyte imbalances. Nevertheless, the differential diagnosis may be difficult
in emergency settings, and sometimes hospitalized infants presenting with salt
wasting are immediately started on steroid therapy to avoid life-threatening
complications, before the correct diagnosis is reached. Physicians involved in
the management of infants with salt-wasting of suspected hormonal origin should
remember that, whenever practicable, a blood sample for the essential hormonal
investigations should be collected before starting steroid therapy, to guide the
subsequent diagnostic procedures and in particular to address the analysis of
candidate genes.
PMID- 27485501
TI - Synthesis and characterization of PEGylated bolaamphiphiles with enhanced
retention in liposomes.
AB - Long-circulating liposomes are typically prepared with poly(ethylene glycol)-
(PEG-) modified lipids, where the lipid portion is inserted in the lipid bilayers
as an anchor and the hydrophilic PEG coats the surface to prevent liposome
aggregation and rapid clearance in vivo. However, these steric protection effects
are compromised upon systemic administration due to low retention of PEGylated
lipids within liposome membranes upon dilution. Hence, a series of PEGylated
bolaamphiphiles (PEG-bolas) were for the first time developed to increase
retention in the lipid bilayer, presumably leading to enhanced integrity of the
PEG protective layer upon dilution. We hypothesized that PEG-bolas with a
sufficiently long hydrophobic domain and rigid central group could predominantly
adopt a membrane-spanning configuration, taking full advantage of steric
protection offered by PEG and enhanced retention in liposomes enabled by the bola
geometry. In this paper, liposomes stabilized by PEG-bolas comprised of a
biphenyl core and twelve-carbon alkyl chain not only exhibited similar storage
and biological stability compared to conventional PEGylated lipid stabilized
liposomes, but also significantly improved retention upon dilution. Our findings
facilitate new designs of liposome-stabilizing agents and can be applied to
improve the delivery efficiency of liposomal delivery vehicles in vivo.
PMID- 27485502
TI - Carboxymethylated lignins with low surface tension toward low viscosity and
highly stable emulsions of crude bitumen and refined oils.
AB - Kraft and organosolv lignins were subjected to carboxymethylation to produce
fractions that were soluble in water, displayed a minimum surface tension as low
as 34mN/m (25 degrees C) and a critical aggregation concentration of ~1.5wt%. The
carboxymethylated lignins (CML), which were characterized in terms of their
degree of substitution ((31)P NMR), elemental composition, and molecular weight
(GPC), were found suitable in the formulation of emulsions with bitumens of ultra
high viscosity, such as those from the Canadian oil sands. Remarkably, the
interfacial features of the CML enabled fuel emulsions that were synthesized in a
very broad range of internal phase content (30-70%). Cryo-replica transmission
electron microscopy, which was used here the first time to assess the morphology
of the lignin-based emulsions, revealed the droplets of the emulsion stabilized
with the modified lignin. The observed drop size (diameters<2MUm) was confirmed
by light scattering, which revealed a normal size distribution. Such
characteristics led to stable emulsified systems that are amenable for a wide
range of applications. Emulsification with CML afforded bitumen emulsions with
very high colloidal stability (no change was noted for over one month) and with a
strong shear thinning behavior. Both features indicate excellent prospects for
storage, transport and spraying, which are relevant in operations for power
generation, which also take advantage of the high heating value of the emulsion
components. The ability of CML to stabilize emulsions and to contribute in their
combustion was tested with light fuels (kerosene, diesel, and jet fuel) after
formulation of high internal phase systems (70% oil) that enabled operation of a
fuel engine. A significant finding is that under certain conditions and compared
to the respective pure fuel, combustion of the O/W emulsions stabilized by CML
presented lower NOx and CO emissions and maintained a relatively high combustion
efficiency. The results highlight the possibilities in high volume application
for lignin biomacromolecules.
PMID- 27485503
TI - High-performance glucose biosensor based on chitosan-glucose oxidase immobilized
polypyrrole/Nafion/functionalized multi-walled carbon nanotubes bio-nanohybrid
film.
AB - A highly electroactive bio-nanohybrid film of polypyrrole (PPy)-Nafion (Nf)
functionalized multi-walled carbon nanotubes (fMWCNTs) nanocomposite was prepared
on the glassy carbon electrode (GCE) by a facile one-step electrochemical
polymerization technique followed by chitosan-glucose oxidase (CH-GOx)
immobilization on its surface to achieve a high-performance glucose biosensor.
The as-fabricated nanohybrid composite provides high surface area for GOx
immobilization and thus enhances the enzyme-loading efficiency. The structural
characterization revealed that the PPy-Nf-fMWCNTs nanocomposite films were
uniformly formed on GCE and after GOx immobilization, the surface porosities of
the film were decreased due to enzyme encapsulation inside the bio-nanohybrid
composite materials. The electrochemical behavior of the fabricated biosensor was
investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy
(EIS), and amperometry measurements. The results indicated an excellent catalytic
property of bio-nanohybrid film for glucose detection with improved sensitivity
of 2860.3MUAmM(-1)cm(-2), the linear range up to 4.7mM (R(2)=0.9992), and a low
detection limit of 5MUM under a signal/noise (S/N) ratio of 3. Furthermore, the
resulting biosensor presented reliable selectivity, better long-term stability,
good repeatability, reproducibility, and acceptable measurement of glucose
concentration in real serum samples. Thus, this fabricated biosensor provides an
efficient and highly sensitive platform for glucose sensing and can open up new
avenues for clinical applications.
PMID- 27485504
TI - Effect of Cavitation Bubble Collapse on the Modification of Solids:
Crystallization Aspects.
AB - This review examines the concepts how cavitation bubble collapse affects
crystalline structure, the crystallization of newly formed structures, and
recrystallization. Although this subject can be discussed in a broad sense across
the area of metastable crystallization, our main focus is discussing specific
examples of the inorganic solids: metal, intermetallics, metal oxides, and
silicon. First, the temperature up to which ultrasound heats solids is discussed.
Cavitation-induced changes in the crystal size of intermetallic phases in binary
AlNi (50 wt % of Ni) alloys allow an estimation of local temperatures on surfaces
and in bulk material. The interplay between atomic solid-state diffusion and
recrystallization during bubble collapses in heterogeneous systems is revealed.
Furthermore, cavitation triggered red/ox processes at solid/liquid interfaces and
their influence on recrystallization are discussed for copper aluminum
nanocomposites, zinc, titanium, magnesium-based materials, and silicon.
Cavitation-driven highly nonequilibrium conditions can affect the thermodynamics
and kinetics of mesoscopic phase formation in heterogeneous systems and in many
cases boost the macroscopic performance of composite materials, notably in
catalytic alloy and photocatalytic semiconductor oxide properties, corrosion
resistance, nanostructured surface biocompatibility, and optical properties.
PMID- 27485505
TI - Ultrasound imaging of splenomegaly as a proxy to monitor colon tumor development
in Apc(min716/+) mice.
AB - Animal models of colon cancer are widely used to understand the molecular
mechanisms and pathogenesis of the disease. These animal models require a
substantial investment of time and traditionally necessitate the killing of the
animal to measure the tumor progression. Several in vivo imaging techniques are
being used in both human clinics and preclinical studies, albeit at high cost and
requiring particular expertise. Here, we report that the progression of
splenomegaly coincides with and positively correlates to colon tumor development
in Apc(min716/+) mice expressing a mutant gene encoding an adenomatous polyposis
coli protein truncated at amino acid 716. Ultrasound image-based spleen size
measurement precisely mirrors splenomegaly development in vivo in the tumor-laden
Apc(min716/+) mice. Moreover, the spleen dimensions extracted from the ultrasound
sonograms are positively correlated with normalized spleen weight and the number
and area of colon tumors. Hence, we propose measuring the spleen size in vivo by
ultrasound imaging as a novel approach to estimate splenomegaly development and
to indirectly monitor colon tumor development in Apc(min716/+) mice. The
widespread use of ultrasound machines in the laboratory setting, coupled with the
fact that it is a noninvasive method, make it a straightforward and useful tool
for monitoring the experimental progress of colon cancer in mice and determining
end points without killing animals strictly for diagnostics purposes.
PMID- 27485506
TI - Comparison of Two Measures of Working Memory Impairments in 220 Adolescents and
Adults With ADHD.
AB - OBJECTIVE: This study tests the hypotheses that (a) adolescents and adults with
ADHD score lower on two normed measures of verbal working memory, relative to
their overall verbal abilities, than the general population and (b) a specific
story memory test is a more sensitive and relevant measure of working memory
impairment than a numerically based test. METHOD: Scores on normed story memory
and numerical memory tests of 220 adolescents and adults with ADHD were corrected
for the individual's verbal abilities and compared with each other and national
norms. RESULTS: Participants with ADHD scored significantly below their verbal
ability measure on both verbal and numerically based memory tests in comparison
with national norms. Scores on verbal memory test were lower than scores for
numerically based memory tests. CONCLUSION: This story memory test is a more
sensitive measure of working memory impairments in adolescents and adults with
ADHD than measures based on recall of numerical data.
PMID- 27485507
TI - Profile of tuberculosis and its response to anti-TB drugs among tuberculosis
patients treated under the TB control programme at Felege-Hiwot Referral
Hospital, Ethiopia.
AB - BACKGROUND: Tuberculosis (TB) is a global concern for both developing and
developed countries. Currently it becomes more complex due to increasing levels
of drug resistance and HIV co-infection. Delayed diagnosis and high case load are
major factors contributing to continued transmission and failure to the treatment
outcome. The study was conducted to determine the profile and treatment outcomes
of TB patients at Felege-Hiwot Referral Hospital. METHODS: We analyzed the
records of 1761 TB patients registered for treatment in Felege Hiwot Referral
Hospital from July 2010 to June 2015. Data on patients' socio-demographic
characteristics, type of TB, HIV status and treatment outcome were analysed.
Descriptive statistics and binary logistic regression models were used to present
data. The odds ratio and the 95 % confidence intervals were calculated. A p-value
of < 0.05 was considered statistical significant. RESULTS: The proportion of
smear positive, smear-negative and extra-pulmonary TB were 205 (11.6 %), 548
(31.1 %) and 1008 (57.2 %), respectively. The overall treatment success rate
accounts 542(80.8 %) with unsuccessful treatment of 129(19.2 %). The treatment
outcome varied by the years from 68.9 to 97.4 %. Among tuberculosis patients,
459(26.1 %) of them were HIV positive. Being HIV positive (AOR = 4.29, 95 % CI,
2.20-8.37 P = 0.001), retreatment (AOR = 5.32, 95 % CI, 1.92-14.3, P = 0.001),
rural residency (AOR = 18.0, 95 % CI, 9.06-37.82, P = 0.001) and the age group of
15-24 years (AOR = 2.91, 95%CI, 1.00-8.45, P = 0.04) showed statistical
significant association for poor treatment outcome. CONCLUSIONS: In the studied
region, the overall treatment success rate was still below the WHO target of
success rate, 85 %. However, the trend of treatment success rate showed a
promising increment. Patients at high risk of unsuccessful treatment outcome
should be identified early and given additional follow-up, medical intervention
and social support.
PMID- 27485508
TI - Pipeline for amplifying and analyzing amplicons of the V1-V3 region of the 16S
rRNA gene.
AB - BACKGROUND: Profiling of 16S rRNA gene sequences is an important tool for testing
hypotheses in complex microbial communities, and analysis methods must be updated
and validated as sequencing technologies advance. In host-associated bacterial
communities, the V1-V3 region of the 16S rRNA gene is a valuable region to
profile because it provides a useful level of taxonomic resolution; however, use
of Illumina MiSeq data for experiments targeting this region needs validation.
RESULTS: Using a MiSeq machine and the version 3 (300 * 2) chemistry, we
sequenced the V1-V3 region of the 16S rRNA gene within a mock community. Nineteen
bacteria and one archaeon comprised the mock community, and 12 replicate
amplifications of the community were performed and sequenced. Sequencing the
large fragment (490 bp) that encompasses V1-V3 yielded a higher error rate (3.6
%) than has been reported when using smaller fragment sizes. This higher error
rate was due to a large number of sequences that occurred only one or two times
among all mock community samples. Removing sequences that occurred one time among
all samples (singletons) reduced the error rate to 1.4 %. Diversity estimates of
the mock community containing all sequences were inflated, whereas estimates
following singleton removal more closely reflected the actual mock community
membership. A higher percentage of the sequences could be taxonomically assigned
after singleton and doubleton sequences were removed, and the assignments
reflected the membership of the input DNA. CONCLUSIONS: Sequencing the V1-V3
region of the 16S rRNA gene on the MiSeq platform may require additional sequence
curation in silico, and improved error rates and diversity estimates show that
removing low-frequency sequences is reasonable. When datasets have a high number
of singletons, these singletons can be removed from the analysis without losing
statistical power while reducing error and improving microbiota assessment.
PMID- 27485509
TI - Intervention to Improve Quality of life for African-AmericaN lupus patients
(IQAN): study protocol for a randomized controlled trial of a unique a la carte
intervention approach to self-management of lupus in African Americans.
AB - BACKGROUND: Systemic Lupus Erythematosus (lupus) is a chronic autoimmune disease
that can impact any organ system and result in life-threatening complications.
African-Americans are at increased risk for morbidity and mortality from lupus.
Self-management programs have demonstrated significant improvements in health
distress, self-reported global health, and activity limitation among people with
lupus. Despite benefits, arthritis self-management education has reached only a
limited number of people. Self-selection of program could improve such trends.
The aim of the current study is to test a novel intervention to improve quality
of life, decrease indicators of depression, and reduce perceived and biological
indicators of stress in African-American lupus patients in South Carolina.
METHODS/DESIGN: In a three armed randomized, wait list controlled trial, we will
evaluate the effectiveness of a patient-centered 'a-la-carte' approach that
offers subjects a variety of modes of interaction from which they can choose as
many or few as they wish, compared to a 'set menu' approach and usual care. This
unique 'a-la-carte' self-management program will be offered to 50 African
American lupus patients participating in a longitudinal observational web-based
SLE Database at the Medical University of South Carolina. Each individualized
intervention plan will include 1-4 options, including a mail-delivered arthritis
kit, addition and access to an online message board, participation in a support
group, and enrollment in a local self-management program. A 'set menu' control
group of 50 lupus patients will be offered a standardized chronic disease self
management program only, and a control group of 50 lupus patients will receive
usual care. Outcomes will include changes in (a) health behaviors, (b) health
status, (c) health care utilization, and (d) biological markers (urinary
catecholamines). DISCUSSION: Such a culturally sensitive educational intervention
which includes self-selection of program components has the potential to improve
disparate trends in quality of life, disease activity, depression, and stress
among African-American lupus patients, as better outcomes have been documented
when participants are able to choose/dictate the content and/or pace of the
respective treatment/intervention program. Since there is currently no "gold
standard" self-management program specifically for lupus, this project may have a
considerable impact on future research and policy decisions. TRIAL REGISTRATION:
NCT01837875 ; April 18, 2013.
PMID- 27485510
TI - Genomic mechanisms for cold tolerance and production of exopolysaccharides in the
Arctic cyanobacterium Phormidesmis priestleyi BC1401.
AB - BACKGROUND: Cyanobacteria are major primary producers in extreme cold ecosystems.
Many lineages of cyanobacteria thrive in these harsh environments, but it is not
fully understood how they survive in these conditions and whether they have
evolved specific mechanisms of cold adaptation. Phormidesmis priestleyi is a
cyanobacterium found throughout the cold biosphere (Arctic, Antarctic and alpine
habitats). Genome sequencing of P. priestleyi BC1401, an isolate from a
cryoconite hole on the Greenland Ice Sheet, has allowed for the examination of
genes involved in cold shock response and production of extracellular polymeric
substances (EPS). EPSs likely enable cyanobacteria to buffer the effects of
extreme cold and by identifying mechanisms for EPS production in P. priestleyi
BC1401 this study lays the way for investigating transcription and regulation of
EPS production in an ecologically important cold tolerant cyanobacterium.
RESULTS: We sequenced the draft genome of P. priestleyi BC1401 and implemented a
new de Bruijn graph visualisation approach combined with BLAST analysis to
separate cyanobacterial contigs from a simple metagenome generated from non
axenic cultures. Comparison of known cold adaptation genes in P. priestleyi
BC1401 with three relatives from other environments revealed no clear differences
between lineages. Genes involved in EPS biosynthesis were identified from the Wzy
and ABC-dependent pathways. The numbers of genes involved in cell wall and
membrane biogenesis in P. priestleyi BC1401 were typical relative to the genome
size. A gene cluster implicated in biofilm formation was found homologous to the
Wps system, although the intracellular signalling pathways by which this could be
regulated remain unclear. CONCLUSIONS: Results show that the genomic
characteristics and complement of known cold shock genes in P. priestleyi BC1401
are comparable to related lineages from a wide variety of habitats, although as
yet uncharacterised cold shock genes in this organism may still exist. EPS
production by P. priestleyi BC1401 likely contributes to its ability to survive
efficiently in cold environments, yet this mechanism is widely distributed
throughout the cyanobacterial phylum. Discovering how these EPS related
mechanisms are regulated may help explain why P. priestleyi BC1401 is so
successful in cold environments where related lineages are not.
PMID- 27485511
TI - Gingival hyperplasia as first sign of recurrence of granulomatosis with
polyangiitis (Wegener's granulomatosis): case report and review of the
literature.
AB - BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly referred to as
Wegener's granulomatosis, is a rare systemic disease of unknown etiology which
can affect all areas of the body, including the oral cavity. The typical oral
manifestations occur as nonspecific erosive/ulcerative lesions of the oral cavity
or appear with hyperplastic gingivitis, a so called "strawberry gingivitis". CASE
PRESENTATION: We report here about an extremely rare case with hyperplastic
gingivitis as the first sign of recurrence of GPA in the absence of oral
manifestations in the primary disease. A 72 year-old female was referred to our
Department of Cranio-Maxillofacial Surgery with hyperplastic gingivitis. The
patient was diagnosed with GPA already eight years before. We referred the
patient to our Clinic of Internal Medicine where she was successfully treated
with rituximab. At the follow-up visit, the patient showed complete remission of
the hyperplastic gingiva. CONCLUSION: The often overlooked oral manifestation may
be interpreted as the first evidence of resurgent GPA in general and therefore
could be pathognostic for the disease. This case affirms the need of health
professionals to be acquainted with orofacial manifestations of rare diseases
such as GPA. As a consequence, dentists will be able to assist in diagnosing GPA
more easily leading to a better prognosis for patients suffering from this
disease.
PMID- 27485512
TI - Making Quality Health Websites a National Public Health Priority: Toward Quality
Standards.
AB - BACKGROUND: Most US adults have limited health literacy skills. They struggle to
understand complex health information and services and to make informed health
decisions. The Internet has quickly become one of the most popular places for
people to search for information about their health, thereby making access to
quality information on the Web a priority. However, there are no standardized
criteria for evaluating Web-based health information. Every 10 years, the US
Department of Health and Human Services' Office of Disease Prevention and Health
Promotion (ODPHP) develops a set of measurable objectives for improving the
health of the nation over the coming decade, known as Healthy People. There are
two objectives in Healthy People 2020 related to website quality. The first is
objective Health Communication and Health Information Technology (HC/HIT) 8.1:
increase the proportion of health-related websites that meet 3 or more evaluation
criteria for disclosing information that can be used to assess information
reliability. The second is objective HC/HIT-8.2: increase the proportion of
health-related websites that follow established usability principles. OBJECTIVE:
The ODPHP conducted a nationwide assessment of the quality of Web-based health
information using the Healthy People 2020 objectives. The ODPHP aimed to
establish (1) a standardized approach to defining and measuring the quality of
health websites; (2) benchmarks for measurement; (3) baseline data points to
capture the current status of website quality; and (4) targets to drive
improvement. METHODS: The ODPHP developed the National Quality Health Website
Survey instrument to assess the quality of health-related websites. The ODPHP
used this survey to review 100 top-ranked health-related websites in order to set
baseline data points for these two objectives. The ODPHP then set targets to
drive improvement by 2020. RESULTS: This study reviewed 100 health-related
websites. For objective HC/HIT-8.1, a total of 58 out of 100 (58.0%) websites met
3 or more out of 6 reliability criteria. For objective HC/HIT-8.2, a total of 42
out of 100 (42.0%) websites followed 10 or more out of 19 established usability
principles. On the basis of these baseline data points, ODPHP set targets for the
year 2020 that meet the minimal statistical significance-increasing objective
HC/HIT-8.1 data point to 70.5% and objective HC/HIT-8.2 data point to 55.7%.
CONCLUSIONS: This research is a critical first step in evaluating the quality of
Web-based health information. The criteria proposed by ODPHP provide methods to
assess website quality for professionals designing, developing, and managing
health-related websites. The criteria, baseline data, and targets are valuable
tools for driving quality improvement.
PMID- 27485513
TI - Prevalence of pathogenic free-living amoeba and other protozoa in natural and
communal piped tap water from Queen Elizabeth protected area, Uganda.
AB - BACKGROUND: Pathogenic water dwelling protozoa such as Acanthamoeba spp.,
Hartmannella spp., Naegleria spp., Cryptosporidium spp. and Giardia spp. are
often responsible for devastating illnesses especially in children and
immunocompromised individuals, yet their presence and prevalence in certain
environment in sub-Saharan Africa is still unknown to most researchers, public
health officials and medical practitioners. The objective of this study was to
establish the presence and prevalence of pathogenic free-living amoeba (FLA),
Cryptosporidium and Giardia in Queen Elizabeth Protected Area (QEPA). METHODS:
Samples were collected from communal taps and natural water sites in QEPA.
Physical water parameters were measured in situ. The samples were processed to
detect the presence of FLA trophozoites by xenic cultivation, Cryptosporidium
oocysts by Ziehl-Neelsen stain and Giardia cysts by Zinc Sulphate floatation
technique. Parasites were observed microscopically, identified, counted and
recorded. For FLA, genomic DNA was extracted for amplification and sequencing.
RESULTS: Both natural and tap water sources were contaminated with FLA,
Cryptosporidium spp. and Giardia spp. All protozoan parasites were more abundant
in the colder rainy season except for Harmannella spp. and Naegleria spp. which
occurred more in the warmer months. The prevalence of all parasites was higher in
tap water than in natural water samples. There was a strong negative correlation
between the presence of Acanthamoeba spp., Hartmannella spp., Cryptosporidium
spp. and Giardia spp. with Dissolved Oxygen (DO) (P < 0.05). The presence of
Cryptosporidium spp. showed a significant positive correlation (P < 0.05) with
conductivity, pH and Total Dissolved Solids (TDS); whereas the presence of
Giardia spp. had only a strong positive correlation with TDS. Molecular
genotyping of FLA produced 7 Acanthamoeba, 5 Echinamoeba, 2 Hartmannella, 1
Bodomorpha, 1 Nuclearia and 1 Cercomonas partial sequences. CONCLUSIONS: All
water collection sites were found to be contaminated with pathogenic protozoa
that could possibly be the cause of a number of silent morbidities and
mortalities among rural households in QEPA. This implies that water used by
communities in QEPA is of poor quality and predisposes them to a variety of
protozoan infections including the FLA whose public health importance was never
reported, thus necessitating adoption of proper water safety measures.
PMID- 27485514
TI - A rational two-step approach to KRAS mutation testing in colorectal cancer using
high resolution melting analysis and pyrosequencing.
AB - BACKGROUND: KRAS mutation testing is mandatory in the management of metastatic
colorectal cancer prior to treatment with anti-EGFR antibodies as patients whose
tumors express mutant KRAS do not benefit from these agents. Although the U.S.
Food and Drug Administration has recently approved two in-vitro diagnostics kits
for determination of KRAS status, there is generally no consensus on the
preferred method and new tests are continuously being developed. Most of these
techniques focus on the hotspot mutations at codons 12 and 13 of the KRAS gene.
METHODS: We describe a two-step approach to KRAS codon 12/13 mutation testing
involving high resolution melting analysis (HRM) followed by pyrosequencing using
the Therascreen KRAS Pyro kit (Qiagen) of only those samples that are not clearly
identified as KRAS wildtype or mutant by HRM. First, we determined KRAS status in
a panel of 61 colorectal cancer samples using both methods to compare technical
performance and concordance of results. Subsequently, we evaluated practicability
and costs of our concept in an independent set of 120 colorectal cancer samples
in a routine diagnostic setting. RESULTS: HRM and pyrosequencing appeared to be
equally sensitive, allowing for clear detection of mutant alleles at a mutant
allele frequency >=12.5 %. Pyrosequencing yielded more exploitable results due to
lower input requirements and a lower rate of analysis failures. KRAS codon 12/13
status was called concordantly for 98.2 % (56/57) of all samples that could be
successfully analysed by both methods and 100 % (19/19) of samples that were
identified mutant by HRM. Reviewing the actual effort and expenses for KRAS
mutation testing in our laboratory revealed, that the selective use of
pyrosequencing for only those samples that could not be analysed by HRM increased
the fraction of valid results from 87.5 % for HRM alone to 99.2 % (119/120) while
allowing for a net reduction of operational costs of >75 % compared to
pyrosequencing alone. CONCLUSIONS: Combination of HRM and pyrosequencing in a two
step diagnostic procedure constitutes a reliable and economic analysis platform
for KRAS mutation testing in colorectal cancer in a clinical setting.
PMID- 27485515
TI - Tumor Growth Suppression Induced by Biomimetic Silk Fibroin Hydrogels.
AB - Protein-based hydrogels with distinct conformations which enable encapsulation or
differentiation of cells are of great interest in 3D cancer research models.
Conformational changes may cause macroscopic shifts in the hydrogels, allowing
for its use as biosensors and drug carriers. In depth knowledge on how 3D
conformational changes in proteins may affect cell fate and tumor formation is
required. Thus, this study reports an enzymatically crosslinked silk fibroin (SF)
hydrogel system that can undergo intrinsic conformation changes from random coil
to beta-sheet conformation. In random coil status, the SF hydrogels are
transparent, elastic, and present ionic strength and pH stimuli-responses. The
random coil hydrogels become beta-sheet conformation after 10 days in vitro
incubation and 14 days in vivo subcutaneous implantation in rat. When
encapsulated with ATDC-5 cells, the random coil SF hydrogel promotes cell
survival up to 7 days, whereas the subsequent beta-sheet transition induces cell
apoptosis in vitro. HeLa cells are further incorporated in SF hydrogels and the
constructs are investigated in vitro and in an in vivo chick chorioallantoic
membrane model for tumor formation. In vivo, Angiogenesis and tumor formation are
suppressed in SF hydrogels. Therefore, these hydrogels provide new insights for
cancer research and uses of biomaterials.
PMID- 27485516
TI - Transcriptomes of a xylose-utilizing industrial flocculating Saccharomyces
cerevisiae strain cultured in media containing different sugar sources.
AB - Lignocellulosic hydrolysates used for bioethanol production contain a mixture of
sugars, with xylose being the second most abundant after glucose. Since xylose is
not a natural substrate for Saccharomyces cerevisiae, recombinant S. cerevisiae
strongly prefers glucose over xylose, and the fermentation rate and ethanol yield
with xylose are both lower than those with glucose. To determine the molecular
basis for glucose and xylose fermentation, we used microarrays to investigate the
transcriptional difference of a xylose-utilizing industrial strain cultured in
both single sugar media and a mixed sugar medium of glucose and xylose. The
transcriptomes were nearly identical between glucose metabolizing cells in the
glucose alone medium and those in the glucose fermentation phase in the mixed
sugar medium. Whereas the transcriptomes highly differed between the xylose
metabolizing cells in the xylose alone medium and those in the xylose
fermentation phase in the mixed sugar medium, and the differences mainly involved
sulfur metabolism. When the transcriptional profiles were compared between
glucose fermentation state and xylose fermentation state, we found the expression
patterns of hexose transporters and glucose signaling pathway differed in
response to different sugar sources, and the expression levels of the genes
involved in gluconeogenesis, the glyoxylate and tricarboxylic acid cycles and
respiration increased with xylose, indicating that the xylose-metabolizing cells
had high requirements for maintenance energy and lacked the carbon catabolite
repression capability. The effect of carbon catabolite repression by glucose
lasted after glucose depletion for specific genes to different extents.
PMID- 27485517
TI - Kinetic studies on recombinant UDP-glucose: sterol 3-O-beta-glycosyltransferase
from Micromonospora rhodorangea and its bioconversion potential.
AB - Kinetics of a recombinant uridine diphosphate-glucose: sterol glycosyltransferase
from Micromonospora rhodorangea ATCC 27932 (MrSGT) were studied using a number of
sterols (including phytosterols) as glycosyl acceptors. The lowest K m value and
the highest catalytical efficiency (k cat/K m) were found when beta-sitosterol
was the glycosyl acceptor in the enzymatic reaction. In contrast to the enzyme's
flexibility toward the glycosyl acceptor substrate, this recombinant enzyme was
highly specific to uridine diphosphate (UDP)-glucose as the donor substrate.
Besides, the UDP-glucose-dependent MrSGT was able to attach one glucose moiety
specifically onto the C-3 hydroxyl group of other phytosterols such as fucosterol
and gramisterol, yielding stereo-specific fucosterol-3-O-beta-D-glucoside and
gramisterol-3-O-beta-D-glucoside, respectively. Based on kinetic data obtained
from the enzyme's reactions using five different sterol substrates, the
significance of the alkene (or ethylidene) side chains on the C-24 position in
the sterol scaffolds was described and the possible relationship between the
substrate structure and enzyme activity was discussed. This is the first report
on the enzymatic bioconversion of the above two phytosteryl 3-O-beta-glucosides,
as well as on the discovery of a stereospecific bacterial SGT which can attach a
glucose moiety in beta-conformation at the C-3 hydroxyl group of diverse sterols,
thus highlighting the catalytic potential of this promiscuous glycosyltransferase
to expand the structural diversity of steryl glucosides.
PMID- 27485518
TI - Process parameters and changes in the microbial community patterns during the
first 240 days of an agricultural energy crop digester.
AB - Commercial biogas production takes place by complex microbial communities
enclosed in controlled "technical ecosystems". Once established, the communities
tend to be resilient towards disturbances, although the relative abundance of
their members may vary. The start-up phase, during which the community
establishes itself, is therefore decisive for the later performance of the
reactor. In this study, we followed the first 240 days of a standard agricultural
energy crop digester consisting of a 400 m(3) plug flow fermenter and a 1000 m(3)
agitated post digester, operated at 40-45 degrees C. The feed consisted of corn
and later grass silage augmented by ground wheat. Changes in both the eubacterial
and methanogenic archaeal communities were followed by automated ribosomal
intergenic spacer analysis (ARISA). In addition the copy number of the methyl
coenzyme reductase A (mcrA)-genes found in all known methanogens were followed by
quantitative PCR, while selected samples from two phases-one early, one late-of
the community structure development were subjected to high throughput sequencing.
Biogas volume and composition (CH4, CO2, H2, H2S, O2), pH, ammonia-N, and
volatile fatty acids (VFA), were measured as part of the routine process control.
VFA/TIC values were calculated on this basis. Whereas the total gas production of
the plant established itself at about 2500 m(3) biogas per day within the first
months, the composition of the microbial communities showed distinct spatial and
temporal differences over the investigated time period. Absolute values for DNA
isolation procedures are difficult to certify, hence comparative results on
community structures obtained using standardized ARISA with identical primers are
of value. Moreover, ARISA patterns can be statistically analyzed to identify
distinct subgroups and transitions between them as well as serial correlations.
Thereby the microbial community and its structural development can be correlated
with statistical relevance to changes in operational (feed) and process
parameters (pH-value, biogas composition). In particular when augmented by deep
sequencing data of judiciously chosen samples, this allows a hitherto unknown
level of insight into the performance of technical biogas plants.
PMID- 27485520
TI - Erratum.
PMID- 27485521
TI - Influence of gamma radiation on the physical and sensory properties of two
Brazilian rice cultivars.
AB - BACKGROUND: Little has been reported about the effects of gamma radiation on the
physical and sensory characteristics of rice. Samples were irradiated with 60 Co
in doses 0, 1, 2 and 5 kGy, on a rate of 0.4 kGy h-1 . RESULTS: The evaluation of
instrumental color showed that increasing doses promoted the yellowing (higher b*
value) of the rice grains. Hardness was decreased and stickiness was increased in
cooked rice with increasing doses. Sensory evaluation using quantitative
descriptive analysis showed that increasing doses promoted higher occurrence of
yellowish appearance, emergence of burnt aroma, and an increase of bitter and
burnt taste. The sensory acceptance test by 9-point hedonic scale showed
alteration of the samples irradiated with 5 kGy in all evaluated attributes
(appearance, color, aroma, taste and texture). The lowest dose (1 kGy), however,
had good acceptability by the panelists. CONCLUSION: Rice may be subjected to 1
kGy dose of gamma radiation without changes or with small changes in physical
properties and with good overall acceptability. (c) 2016 Society of Chemical
Industry.
PMID- 27485519
TI - Physical activity and the risk of gestational diabetes mellitus: a systematic
review and dose-response meta-analysis of epidemiological studies.
AB - Physical activity has been inconsistently associated with risk of gestational
diabetes mellitus in epidemiological studies, and questions remain about the
strength and shape of the dose-response relationship between the two. We
therefore conducted a systematic review and meta-analysis of cohort studies and
randomized trials on physical activity and gestational diabetes mellitus. PubMed,
Embase and Ovid databases were searched for cohort studies, and randomized
controlled trials of physical activity and risk of gestational diabetes mellitus,
up to August 5th 2015. Summary relative risks (RRs) were estimated using a random
effects model. Twenty-five studies (26 publications) were included. For total
physical activity the summary RR for high versus low activity was 0.62 (95 % CI
0.41-0.94, I2 = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36-1.21, I2 = 0
%, n = 3) during pregnancy. For leisure-time physical activity the respective
summary RRs for high versus low activity was 0.78 (95 % CI 0.61-1.00, I2 = 47 %,
n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64-1.00, I2 = 17 %, n = 17)
during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI
0.49-1.01, I2 = 72.6 %, n = 3) per increment of 5 h/week and for activity during
pregnancy was 0.98 (95 % CI 0.87-1.09, I2 = 0 %, n = 3) per 5 h/week. There was
evidence of a nonlinear association between physical activity before pregnancy
and the risk of gestational diabetes mellitus, pnonlinearity = 0.005, with a
slightly steeper association at lower levels of activity although further
reductions in risk were observed up to 10 h/week. There was also evidence of
nonlinearity for physical activity in early pregnancy, pnonlinearity = 0.008,
with no further reduction in risk above 8 h/week. There was some indication of
inverse associations between walking (before and during pregnancy) and vigorous
activity (before pregnancy) and the risk of gestational diabetes mellitus. This
meta-analysis suggests that there is a significant inverse association between
physical activity before pregnancy and in early pregnancy and the risk of
gestational diabetes mellitus. Further studies are needed to clarify the
association between specific types and intensities of activity and gestational
diabetes mellitus.
PMID- 27485522
TI - A generalized analytic solution to the win ratio to analyze a composite endpoint
considering the clinical importance order among components.
AB - A composite endpoint consists of multiple endpoints combined in one outcome. It
is frequently used as the primary endpoint in randomized clinical trials. There
are two main disadvantages associated with the use of composite endpoints: a) in
conventional analyses, all components are treated equally important; and b) in
time-to-event analyses, the first event considered may not be the most important
component. Recently Pocock et al. (2012) introduced the win ratio method to
address these disadvantages. This method has two alternative approaches: the
matched pair approach and the unmatched pair approach. In the unmatched pair
approach, the confidence interval is constructed based on bootstrap resampling,
and the hypothesis testing is based on the non-parametric method by Finkelstein
and Schoenfeld (1999). Luo et al. (2015) developed a close-form variance
estimator of the win ratio for the unmatched pair approach, based on a composite
endpoint with two components and a specific algorithm determining winners, losers
and ties. We extend the unmatched pair approach to provide a generalized
analytical solution to both hypothesis testing and confidence interval
construction for the win ratio, based on its logarithmic asymptotic distribution.
This asymptotic distribution is derived via U-statistics following Wei and
Johnson (1985). We perform simulations assessing the confidence intervals
constructed based on our approach versus those per the bootstrap resampling and
per Luo et al. We have also applied our approach to a liver transplant Phase III
study. This application and the simulation studies show that the win ratio can be
a better statistical measure than the odds ratio when the importance order among
components matters; and the method per our approach and that by Luo et al.,
although derived based on large sample theory, are not limited to a large sample,
but are also good for relatively small sample sizes. Different from Pocock et al.
and Luo et al., our approach is a generalized analytical method, which is valid
for any algorithm determining winners, losers and ties. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27485523
TI - Ectopic Expression of DREB Transcription Factor, AtDREB1A, Confers Tolerance to
Drought in Transgenic Salvia miltiorrhiza.
AB - Drought decreases crop productivity more than any other type of environmental
stress. Transcription factors (TFs) play crucial roles in regulating plant
abiotic stress responses. The Arabidopsis thaliana gene DREB1A/CBF3, encoding a
stress-inducible TF, was introduced into Salvia miltiorrhiza Ectopic expression
of AtDREB1A resulted in increased drought tolerance, and transgenic lines had
higher relative water content and Chl content, and exhibited an increased
photosynthetic rate when subjected to drought stress. AtDREB1A transgenic plants
generally displayed lower malondialdehyde (MDA), but higher superoxide dismutase
(SOD), catalase (CAT) and peroxidase (POD) activities under drought stress. In
particular, plants with ectopic AtDREB1A expression under the control of the
stress-induced RD29A promoter exhibited more tolerance to drought compared with
p35S::AtDREB1A transgenic plants, without growth inhibition or phenotypic
aberrations. Differential gene expression profiling of wild-type and
pRD29A::AtDREB1A transgenic plants following drought stress revealed that the
expression levels of various genes associated with the stress response,
photosynthesis, signaling, carbohydrate metabolism and protein protection were
substantially higher in transgenic plants. In addition, the amount of salvianolic
acids and tanshinones was significantly elevated in AtDREB1A transgenic S.
miltiorrhiza roots, and most of the genes in the related biosynthetic pathways
were up-regulated. Together, these results demonstrated that inducing the
expression of a TF can effectively regulate multiple genes in the stress response
pathways and significantly improve the resistance of plants to abiotic stresses.
Our results also suggest that genetic manipulation of a TF can improve production
of valuable secondary metabolites by regulating genes in associated pathways.
PMID- 27485524
TI - Individual factors, neighborhood social context and asthma at age 5 years.
AB - OBJECTIVE: Childhood asthma is a major public health problem and its development
is multifactorial. We examined whether neighborhood cohesion and disorder were
associated with caregiver-report of asthma at age 5 years. METHODS: This study is
a secondary data analysis of the 2011-2012 United States National Survey of
Children's Health. Data were available for 4680 children, age 5 years old born at
term or preterm with birthweight >2500 g. Neighborhood disorder and cohesion were
assessed based on caregivers' responses to validated questionnaires. Child asthma
diagnosis was reported by the caregiver. Multivariable logistic regression was
used to examine the relationship between these neighborhood factors and caregiver
report of child asthma, while accounting for individual level covariates.
RESULTS: Approximately two-thirds of the 4680 children were White and lived in
households with income >400% of federal poverty line. Asthma was present in 399
(9%) children. Child female sex was associated with reduced risk of caregiver
reported asthma while non-Hispanic Black race and having smokers in the household
were independently associated with increased risk in multivariable models. In
these models, neighborhood disorder was significantly associated with asthma
(adjusted Odds Ratio [aOR] 1.70, 95% Confidence Interval [CI] 1.04-2.78), while
neighborhood cohesion was not (aOR 0.93, 95% CI 0.51-1.68). CONCLUSION: Even
after adjustment for several individual level factors, neighborhood disorder was
associated with caregiver-report of asthma in this nationally representative
sample of 5-year-old children. Further research is needed to better understand
how risk factors at different levels of the socio-ecological framework may
interact to affect childhood asthma development.
PMID- 27485526
TI - Nanostructuration of PEDOT in Porous Coordination Polymers for Tunable Porosity
and Conductivity.
AB - A series of conductive porous composites were obtained by the polymerization of
3,4-ethylenedioxythiophene (EDOT) in the cavities of MIL-101(Cr). By controlling
the amount of EDOT loaded into the host framework, it was possible to modulate
the conductivity as well as the porosity of the composite. This approach yields
materials with a reasonable electronic conductivity (1.1 * 10(-3) S.cm(-1)) while
maintaining high porosity (SBET = 803 m(2)/g). This serves as a promising
strategy for obtaining highly nanotextured conductive polymers with very high
accessibility for small gas molecules, which are beneficial to the fabrication of
a chemiresistive sensor for the detection of NO2.
PMID- 27485525
TI - Assessing postural stability via the correlation patterns of vertical ground
reaction force components.
AB - BACKGROUND: Many methods have been proposed to assess the stability of human
postural balance by using a force plate. While most of these approaches
characterize postural stability by extracting features from the trajectory of the
center of pressure (COP), this work develops stability measures derived from
components of the ground reaction force (GRF). METHODS: In comparison with
previous GRF-based approaches that extract stability features from the GRF
resultant force, this study proposes three feature sets derived from the
correlation patterns among the vertical GRF (VGRF) components. The first and
second feature sets quantitatively assess the strength and changing speed of the
correlation patterns, respectively. The third feature set is used to quantify the
stabilizing effect of the GRF coordination patterns on the COP. RESULTS: In
addition to experimentally demonstrating the reliability of the proposed
features, the efficacy of the proposed features has also been tested by using
them to classify two age groups (18-24 and 65-73 years) in quiet standing. The
experimental results show that the proposed features are considerably more
sensitive to aging than one of the most effective conventional COP features and
two recently proposed COM features. CONCLUSIONS: By extracting information from
the correlation patterns of the VGRF components, this study proposes three sets
of features to assess human postural stability during quiet standing. As
demonstrated by the experimental results, the proposed features are not only
robust to inter-trial variability but also more accurate than the tested COP and
COM features in classifying the older and younger age groups. An additional
advantage of the proposed approach is that it reduces the force sensing
requirement from 3D to 1D, substantially reducing the cost of the force plate
measurement system.
PMID- 27485527
TI - MicroRNA-610 is downregulated in glioma cells, and inhibits proliferation and
motility by directly targeting MDM2.
AB - The expression of microRNA (miR)-610 has previously been reported to be
downregulated in gastric cancer and hepatocellular carcinoma. However, miR-610
has yet to be investigated in human glioma. In the present study, miR-610
expression was analyzed by reverse transcription-quantitative polymerase chain
reaction. Post-transfection with miR-610 mimics and inhibitors, MTT assay, cell
migration and invasion assays, western blot analysis and a luciferase assay were
performed in glioma cell lines. The results demonstrated that miR-610 was
downregulated in glioma tissues compared with their normal adjacent tissues and
normal brain tissues (P<0.05). The reduced expression levels of miR-610 were
associated with World Health Organization grade and the Karnofsky performance
status of patients with glioma. Furthermore, the present study revealed that miR
610 inhibited cell growth, migration and invasion in glioma cells. To the best of
our knowledge, the present study is the first to provide evidence suggesting that
miR-610 directly targets MDM2 proto-oncogene E3 ubiquitin protein ligase to
function as a tumor suppressor in glioma. These results indicate that miR-610 may
be investigated as a target for therapeutic drugs designed to treat glioma.
PMID- 27485528
TI - Operative Duration and Risk of Surgical Site Infection in Neurosurgery.
AB - BACKGROUND: The association of surgical duration with the risk of surgical site
infection (SSI) has not been quantified in neurosurgery. We investigated the
association of operative duration in neurosurgical procedures with the incidence
of SSI. METHODS: We performed a retrospective cohort study involving patients who
underwent neurosurgical procedures from 2005 to 2012 and were registered in the
American College of Surgeons National Quality Improvement Project registry. To
control for confounding, we used multivariable regression models and propensity
score conditioning. RESULTS: During the study period there were 94,744 patients
who underwent a neurosurgical procedure and met the inclusion criteria. Of these
patients, 4.1% developed a postoperative SSI within 30 days. Multivariable
logistic regression showed an association between longer operative duration with
higher incidence of SSI (odds ratio [OR], 1.18; 95% confidence interval [CI],
1.16-1.20). Compared with procedures of moderate duration (third quintile, 40th
60th percentile), patients undergoing the longest procedures (>80th percentile)
had higher odds (OR, 2.07; 95% CI, 1.86-2.31) of developing SSI. The shortest
procedures (<20th percentile) were associated with decreased incidence of SSI
(OR, 0.72; 95% CI, 0.61-0.83) compared with those of moderate duration. The same
associations were present in propensity score adjusted models and models
stratified by subgroups of cranial, spinal, peripheral nerve, and carotid
procedures. CONCLUSIONS: In a cohort of patients from a national prospective
surgical registry, longer operative duration was associated with increased
incidence of SSI for neurosurgical procedures. These results can be used by
neurosurgeons to inform operative management and to stratify patients with regard
to SSI risk.
PMID- 27485529
TI - Evaluation of the Predictive Value of Intraoperative Changes in Motor-Evoked
Potentials of Caudal Cranial Nerves for the Postoperative Functional Outcome.
AB - OBJECTIVE: The predictive value of changes in intraoperatively acquired motor
evoked potentials (MEPs) of the lower cranial nerves (LCN) IX-X (glossopharyngeal
vagus nerve) and CN XII (hypoglossal nerve) on operative outcomes was
investigated. METHODS: MEPs of CN IX-X and CN XII were recorded intraoperatively
in 63 patients undergoing surgery of the posterior cranial fossa. We correlated
the changes of the MEPs with postoperative nerve function. RESULTS: For CN IX-X,
we found a correlation between the amplitude of the MEP ratio and uvula deviation
(P = 0.028) and the amplitude duration of the MEP and gag reflex function (P =
0.027). Patients with an MEP ratio of the glossopharyngeal-vagus amplitude <=1.47
MUV had a 3.4 times increased risk of developing a uvula deviation. Patients with
a final MEP duration of the CN IX-X <=11.6 milliseconds had a 3.6 times increased
risk for their gag reflex to become extinct. CONCLUSIONS: Our study greatly
contributes to the current knowledge of intraoperative MEPs as a predictor for
postoperative cranial nerve function. We were able to extent previous findings on
MEP values of the facial nerve on postoperative nerve function to 3 additional
cranial nerves. Finding reliable predictors for postoperative nerve function is
of great importance to the overall quality of life for a patient undergoing
surgery of the posterior cranial fossa.
PMID- 27485530
TI - Analysis of Treatment Tolerance and Factors Associated with Overall Survival in
Elderly Patients with Glioblastoma.
AB - BACKGROUND: As the population ages, the proportion of elderly patients with
glioblastomas has increased. Recently, many researchers have focused on the
treatments available to and prognoses in elderly patients with glioblastomas.
METHODS: We conducted a retrospective study of glioblastoma patients aged 60
years old or older who were treated at the Neurosurgery Center at Beijing Tiantan
Hospital from 2012 to 2014. Their clinical features, immunohistochemical
characteristics, treatments, and outcomes were evaluated to determine treatment
tolerance and identify prognostic factors. RESULTS: Among the 70 included
patients, the median survival time was 15 months. In the univariate analysis,
patients who underwent a gross total resection had longer overall survival times
than patients who had a subtotal resection (P < 0.05), and patients who received
postoperative adjuvant therapy had longer overall survival times than those with
no postoperative adjuvant therapy (P < 0.05). The expression of the p53 protein
significantly affected overall survival. Patients with low p53 protein expression
had a median survival of 17 months, whereas those who had high p53 protein
expression had a median survival of 11.50 months (P < 0.05). Undergoing a gross
total resection, receiving postoperative adjuvant therapy and having low p53
protein expression were factors that independently contributed to longer overall
survival times in multivariate analysis. CONCLUSIONS: Maximal safe surgical
resection followed by radiotherapy with concurrent and adjuvant temozolomide
significantly prolonged overall survival times and was well tolerated in elderly
patients with glioblastomas. In addition, low p53 protein expression was a
significant favorable prognostic indicator in this population.
PMID- 27485531
TI - Analysis of recruitment in a pragmatic observational study on C-reactive protein
point-of-care testing in primary care.
AB - INTRODUCTION: Failure to recruit all eligible study patients can lead to biased
results. Little is known on selective patient recruitment in studies on
implementation of diagnostic devices. OBJECTIVES: The aim of this observational
study was to measure recruitment of patients in an implementation study in
primary care on use of point-of-care (POC) C-reactive protein (CRP) and to
evaluate recruitment bias and its impact on the study endpoint. METHODS: In a
cross-sectional observational study on POC CRP implementation and related
antibiotics prescribing, we compared included patients with all eligible patients
to assess the representativeness of the included subjects. Eligible patients were
adults presenting with acute cough in primary care between March and September
2012. The frequency of POC CRP testing and the proportion of prescribed
antibiotics were compared between recruited and non-recruited patients. As
measure of bias, odds ratios (ORs) with accompanying 95% confidence intervals
(CIs) for the association between CRP level (<20 mg/l or not) and antibiotic
prescribing were computed. RESULTS: Of all 1473 eligible patients 348 (24%) were
recruited. In recruited patients, POC CRP tests were conducted and antibiotics
prescribed more frequently as compared to non-recruited patients (81% versus 6%
and 44% versus 29%, respectively). The ORs were 18.2 (95%CI: 9.6-34.3), 30.5
(95%CI: 13.2-70.3) and 3.8 (95%CI: 0.9-14.8) respectively in all eligible
patients, the recruited and the non-recruited patients. CONCLUSION: Selective
recruitment resulted in an overestimation of POC CRP test use and antibiotic
prescribing.
PMID- 27485532
TI - Anti-aging treatments slow propagation of synucleinopathy by restoring lysosomal
function.
AB - Aging is the major risk factor for neurodegenerative diseases that are also
associated with impaired proteostasis, resulting in abnormal accumulation of
protein aggregates. However, the role of aging in development and progression of
disease remains elusive. Here, we used Caenorhabditis elegans models to show that
aging-promoting genetic variations accelerated the rate of cell-to-cell
transmission of SNCA/alpha-synuclein aggregates, hallmarks of Parkinson disease,
and the progression of disease phenotypes, such as nerve degeneration, behavioral
deficits, and reduced life span. Genetic and pharmacological anti-aging
manipulations slowed the spread of aggregates and the associated phenotypes.
Lysosomal degradation was significantly impaired in aging models, while anti
aging treatments reduced the impairment. Transgenic expression of hlh-30p::hlh
30, the master controller of lysosomal biogenesis, alleviated intercellular
transmission of aggregates in the aging model. Our results demonstrate that the
rate of aging closely correlates with the rate of aggregate propagation and that
general anti-aging treatments can slow aggregate propagation and associated
disease progression by restoring lysosomal function.
PMID- 27485534
TI - A quantile regression model for failure-time data with time-dependent covariates.
AB - Since survival data occur over time, often important covariates that we wish to
consider also change over time. Such covariates are referred as time-dependent
covariates. Quantile regression offers flexible modeling of survival data by
allowing the covariates to vary with quantiles. This article provides a novel
quantile regression model accommodating time-dependent covariates, for analyzing
survival data subject to right censoring. Our simple estimation technique assumes
the existence of instrumental variables. In addition, we present a doubly-robust
estimator in the sense of Robins and Rotnitzky (1992, Recovery of information and
adjustment for dependent censoring using surrogate markers. In: Jewell, N. P.,
Dietz, K. and Farewell, V. T. (editors), AIDS Epidemiology. Boston: Birkhaauser,
pp. 297-331.). The asymptotic properties of the estimators are rigorously
studied. Finite-sample properties are demonstrated by a simulation study. The
utility of the proposed methodology is demonstrated using the Stanford heart
transplant dataset.
PMID- 27485533
TI - Re-irradiation for locoregionally recurrent tumors of the thorax: a single
institution, retrospective study.
AB - BACKGROUND: Re-irradiation (re-RT) of the thorax is challenging due to the impact
of prior therapies on normal tissues, and there are few reports of definitive re
RT. The treatment toxicities and efficacy of re-RT are not well known. The aim of
the present study was to assess the safety and efficacy of definitive re-RT of
the thorax. METHODS: Patients who were treated with thoracic re-RT between March
2007 and December 2014 were retrospectively analyzed. Primary and re-irradiation
plans were required to have an overlap of dose distributions for the 80 % isodose
level. All doses were recalculated to an equivalent dose of 2 Gy per fraction
(EQD2). When possible, analysis of dose accumulation was carried out using the
medical image merge (MIM) ((r)) software program (version 6.5, MIM Software Inc.,
Cleveland, OH). Administration dosages for organs at risk were defined. RESULTS:
Fourteen (67 %) and seven (33 %) patients with non-small cell carcinoma (NSCLC)
and small cell carcinoma (SCLC), respectively, were identified. The patients'
median age was 72 (range 53-85) years. Fifteen patients (71 %) had "proximal"
tumors, defined as tumors at the distal 2 cm of the trachea, carina, and main
bronchi. The median interval from initial RT to re-RT was 26.8 (range 11.4-92.3)
months. Re-RT was delivered by X-ray beam and proton beam therapy in 20 (95 %)
patients and 1 (5 %) patient, respectively. The median radiation dose of re-RT
was 60 (range 54-87.5) Gy10 and 50 (range 50.0-87.5) Gy10 for patients with NSCLC
and SCLC, respectively. Grade 3 acute radiation pneumonitis occurred in only one
patient. There were no other serious complications. The median follow-up time was
22.1 (range 2.3-56.4) months. The median local progression-free survival time
(LPFS) and overall survival time (OS) were 12.9 (95 % confidence interval (CI):
8.9-27.9) months and 31.4 (95 % CI: 16.9-45.9) months, respectively. Patients
receiving >= 60 Gy10 at re-RT had longer LPFS (p = 0.04). CONCLUSIONS: Good
safety with longer OS than in previous reports was demonstrated. Re-RT seems to
be a promising treatment option. Further study to define the risk-benefit ratios
is necessary.
PMID- 27485535
TI - Evidence for the Absence of Stimulus Quality Differences in Tests of the Accuracy
of Sexual Orientation Judgments: A Reply to Cox, Devine, Bischmann, and Hyde
(2016).
AB - An article recently published in this journal (Cox, Devine, Bischmann, & Hyde,
2016) questioned the validity of existing research on the accurate judgment of
sexual orientation from photographs of faces. Specifically, those authors
reported a confound in their stimuli whereby the photos of sexual minorities (gay
men and lesbians) were of higher quality than the photos of heterosexuals. Based
on this finding, they concluded that the accuracy in judging sexual orientation
from faces demonstrated in the broader literature is an artifact of stimulus
quality differences. Here, we addressed this claim by systematically testing the
numerous photo sets that we have used in 61 studies documenting accurate
judgments of sexual orientation from facial cues published since 2007. Contrary
to their claim, the overwhelming majority of studies (93%) showed no significant
differences in photo quality according to sexual orientation. Of those that did
show differences, most revealed that heterosexual targets' photos were actually
of higher quality than sexual minority targets' photos - opposite of what Cox et
al. found. In addition, we highlight additional research using stimuli equated
for quality differences overlooked in the recent article by Cox et al., lending
further support to the conclusion that sexual orientation is legible from
multiple sensory cues.
PMID- 27485536
TI - Unilateral hippocampal inactivation or lesion selectively impairs remote
contextual fear memory.
AB - RATIONALE: Contextual fear memory depends on the hippocampus, but the role of
unilateral hippocampus in this type of memory remains unclear. OBJECTIVES:
Herein, pharmacological inactivation or excitotoxic lesions were used to study
the role of unilateral hippocampus in the stages of contextual fear memory.
RESULTS: The pharmacological experiments revealed that compared with the control
groups, unilateral hippocampal blockade did not impair 1-day recent memory
following learning, whereas bilateral hippocampal blockade significantly impaired
this memory. The lesion experiments showed that compared with the control groups,
the formed contextual fear memory was retained for 7 days and that 30-day remote
memory was markedly reduced in unilateral hippocampal lesion groups. CONCLUSIONS:
These results indicate that an intact bilateral hippocampus is required for the
formation of remote memory and that unilateral hippocampus is sufficient for
recent contextual fear memory.
PMID- 27485537
TI - BSA and ABCB1 polymorphism affect the pharmacokinetics of sunitinib and its
active metabolite in Asian mRCC patients receiving an attenuated sunitinib dosing
regimen.
AB - PURPOSE: An attenuated dosing (AD) sunitinib regimen of 37.5 mg daily has been
suggested to reduce the toxicity reported with the standard dosing regimen to
metastatic renal cell carcinoma (mRCC) patients. The aim of this study was to
characterize the population pharmacokinetic (PK) properties of sunitinib and
SU12662, the active metabolite, in patients receiving the AD regimen and to
ascertain significant covariates influencing PK parameters. METHODS: Thirty-one
mRCC patients receiving AD sunitinib regimen were included. Plasma samples were
collected on day 29 of each treatment cycle after the start of the therapy.
Nonlinear mixed-effects modeling was applied to estimate the population PK
properties of sunitinib and SU12662 as well as the effect of covariates on PK
parameters. Monte Carlo simulation was also performed to predict the total trough
level (TTL) of sunitinib and SU12662. RESULTS: Sunitinib population means for
CL/F and V d /F central were 13.8 L/h and 1720 L, respectively. SU12662
population means for CL/F and V d /F were 42.1 L/h and 1410 L, respectively. Body
surface area (BSA) and ABCB1 polymorphism significantly influenced the CL/F
variability of sunitinib: CL/F parent = 13.8 * exp((BSA - 1.75) * 2.08 + (ABCB1
genotype - 0.67) * 0.61), ABCB1-0: wild genotype, 1: mutant genotype. The effect
size of ABCB1 mutant genotype and BSA greater than 1.75 m(2) in relation to
sunitinib clearance was 31.14 % (p = 0.006) and 22.11 % (p = 0.011),
respectively, relative to the reference group. CONCLUSIONS: Adjusting doses of
sunitinib according to BSA and ABCB1 polymorphism in Asian mRCC patients may be
recommended for sufficient attainment of a target TTL of sunitinib and its
metabolite.
PMID- 27485538
TI - Myelosuppression by chemotherapy in obese patients with gynecological cancers.
AB - PURPOSE: The American Society of Clinical Oncology provides clinical practice
guidelines for appropriate cytotoxic chemotherapy dosing for obese adult patients
with cancer. The panel recommends that actual body weight should be used when
selecting cytotoxic chemotherapy doses regardless of obesity status. However,
there have been no reports regarding the appropriate cytotoxic chemotherapy
dosing for obese Japanese patients with cancer. PATIENTS AND METHODS: We
collected data from 216 gynecological cancer patients who were treated with at
least one course of a paclitaxel and carboplatin (TC) regimen or a docetaxel and
carboplatin (DC) regimen at Niigata University Medical and Dental Hospital from
July 2006 to April 2014. Patients were divided into three groups according to
body mass index (BMI): obese (BMI >= 25), normal (BMI 18.5-24.9), and underweight
(BMI < 18.5), as defined by the Japan Society for the Study of Obesity. We
analyzed hematological toxicities by full weight-based chemotherapy in each
group. RESULTS: The rates of grade 3/4 leukocytopenia, neutropenia, and
thrombocytopenia were not significantly different among the three BMI groups on
all patient analyses. For the TC regimen, the obese and normal groups had
significantly lower leukocytopenia (grade 3/4) rates than did the underweight
group. Also, significant positive correlations between BMI and the nadirs of
leukocytes, neutrophils, platelets, and hemoglobin were observed. For the DC
regimen, no significant difference was observed among the BMI groups and the rate
of grade 3/4 hematological toxicities. CONCLUSIONS: We did not observe stronger
myelosuppression in obese cancer patients compared with non-obese cancer
patients. Therefore, the cytotoxic chemotherapy dose should be calculated by the
actual body weight and unnecessary dose reduction should be avoided.
PMID- 27485539
TI - KLF4: A new player in plasma cell development.
PMID- 27485541
TI - Corrigendum to "Nonmuscle Myosin-Dependent Synthesis of Type I Collagen..." [J
Mol Biol. 27;401(4):2010: 564-578].
PMID- 27485540
TI - The Role of Intracoronary Plaque Imaging with Intravascular Ultrasound, Optical
Coherence Tomography, and Near-Infrared Spectroscopy in Patients with Coronary
Artery Disease.
AB - The development of multiple diagnostic intracoronary imaging modalities has
increased our understanding of coronary atherosclerotic disease. These imaging
modalities, intravascular ultrasound (IVUS), optical coherence tomography (OCT),
and near-infrared spectroscopy (NIRS), have provided a method to study plaques
and introduced the concept of plaque vulnerability. They are being increasingly
used for percutaneous coronary intervention (PCI) optimization and are invaluable
tools in research studying the pathophysiology of acute coronary syndrome (ACS),
in-stent thrombosis and in-stent restenosis. IVUS has the ability to visualize
the intracoronary lumen and the vessel wall and can be used to detect early
atherosclerotic disease even in the setting of positive arterial remodeling.
Studies supporting the use of IVUS to optimize stent deployment and apposition
have shown a significant reduction in cardiovascular events. OCT provides even
higher resolution imaging and near microscopic detail of plaques, restenoses, and
thromboses; thus, it can identify the etiology of ACS. Ongoing trials are
evaluating the role of OCT in PCI and using OCT to study stent endothelialization
and neointimal proliferation. NIRS is a modality capable of localizing and
quantifying lipid core burden. It is usually combined with IVUS and is used to
characterize plaque composition. The benefits of NIRS in the setting of ACS have
been limited to case reports and series. The utilization of all these
intracoronary imaging modalities will continue to expand as their indications for
clinical use and research grow. Studies to support their use for PCI optimization
resulting in improved outcomes with potential to prevent downstream events are
ongoing.
PMID- 27485542
TI - Timing of initiation of renal replacement therapy for acute kidney injury: a
systematic review and meta-analysis of randomized-controlled trials.
AB - BACKGROUND: The effects of early renal replacement therapy (RRT) on mortality and
renal recovery in patients with acute kidney injury (AKI) remain controversial. A
systematic review and meta-analysis of randomized-controlled trials (RCTs) was
performed. METHODS: MEDLINE, EMBASE and the Cochrane Library database (Cochrane
Central Register of Controlled Trials) were searched to identify RCTs,
investigating the effects of early RRT on patients with AKI. RESULTS: Six studies
with a total of 1257 participants were included in this meta-analysis. Compared
to late RRT, early RRT did not reduce the risk of mortality (RR 0.93, 95 % CI
0.68-1.26) or affect renal recovery (RR 0.88, 95 % CI 0.48-1.62) or composite
endpoint (death or dialysis dependence) (RR 0.91, 95 % CI 0.71-1.17). There was
no significant difference in adverse events in the analysis, between the early
RRT and late RRT arms. CONCLUSIONS: Early initiation of RRT for patients with AKI
is not associated with decreased overall mortality or a delayed renal recovery
rate. The optimal time to initiate RRT remains uncertain. Large scale and
adequately powered RCTs are needed to detect the effects of early initiation of
RRT in AKI patients.
PMID- 27485543
TI - MicroRNA-363 and GATA-1 are regulated by HIF-1alpha in K562 cells under hypoxia.
AB - The aim of the present study was to investigate regulatory relationships among
hypoxia-inducible factor-1alpha (HIF-1alpha), microRNA and erythroid
transcription factors. K562 cells were transfected with HIF-1alpha knockout or
with overexpression lentivirus of plasmid (MOI 10). The cells were divided into 3
groups: the negative control, overexpressing and interference groups. The cells
were cultured under normoxia and hypoxia. Expression of miR-17*, miR-363 and miR
574-5p in the three groups was determined by quantitative PCR. Expression levels
of erythroid transcription factor mRNAs such as GATA-1/GATA-2 and nuclear factor
erythroid 2 (NF-E2) were measured using RT-qPCR while the protein expression was
studied using western blot analysis. Under normoxia or hypoxia, the levels of miR
17*, miR-363 and miR-574-5p in the overexpression group were higher than those in
the other groups. Differences were statistically significant (P<0.05). Under
hypoxia, the level of miR-363 in the interference group was less than that in the
negative control group and difference was statistically significant (P<0.05). The
level of GATA-1 mRNA in the overexpression group was higher than that in the
negative control group, however, in the interference group the level was lower
than that in the overexpression group under both normoxic and hypoxic conditions.
The level of GATA-2 mRNA in the interference group was higher than that in other
two groups under normoxic or hypoxic conditions. The NF-E2 mRNA was reversely
related to GATA-2. The levels of HIF-1alpha, GATA-1 and NF-E2 mRNAs in the
negative control under hypoxia were higher than those of normoxia. The level of
HIF-1alpha mRNA in the overexpression group in hypoxia was lower than that in
normoxia, while the GATA-1 and GATA-2 mRNA showed a reverse association. The
levels of HIF-1alpha and GATA-2 mRNA in the interference group under hypoxia were
higher compared to those of normoxia. Differences were statistically significant
(P<0.05). Western blot results suggested that GATA-1, GATA-2 and NF-E2 protein
expression correlated with changes in their respective mRNA transcription levels.
The results therefore suggested that GATA-l and miR-363 were involved in the
regulation of hematopoiesis via the HIF-1alpha pathway in K562 cells under
hypoxic condition. The hsa-miR-17* and hsa-miR-574-5p were not entirely dependent
on HIF-1alpha, suggesting possible complex regulatory mechanisms involved in
hypoxia.
PMID- 27485545
TI - Awareness of and compliance with healthy oral habits reported by children and
their parents in Democratic People's Republic of Korea after a preventive
programme.
AB - OBJECTIVE: The study aimed to examine awareness of and compliance with healthy
oral habits reported by children and their parents in Pyongyang, Democratic
People's Republic of Korea (DPRK), after a preventive programme. MATERIALS AND
METHODS: The data were collected in 2013 with self-completed, partly structured
questionnaires from 1994 children aged 10 and 13 years and from 200 parents.
Association between awareness of and compliance with healthy oral habits reported
by the children and their parents was evaluated using Chi square tests and
multivariate logistic regression analyses, children's oral health habits
according to themselves and their parents were analysed using McNemar's test.
RESULTS: Both children and their parents seemed to be familiar with healthy oral
habits, although the awareness was not directly related to the reports of the
children's oral practices. Most of the children reported brushing their teeth at
least twice a day, using fluoride toothpaste and drinking water for thirst but
frequent sweet snacking was common. Children's and their parents' reports were
consistent with regard to sweet snacking frequency (p = 0.736) and the main
thirst quencher (p = 0.349). CONCLUSIONS: Awareness of healthy oral habits
appeared to be good among children and their parents. Unhealthy oral habits
seemed to coincide with one another.
PMID- 27485544
TI - Quantitative proteomic analysis for novel biomarkers of buccal squamous cell
carcinoma arising in background of oral submucous fibrosis.
AB - BACKGROUND: In South and Southeast Asian, the majority of buccal squamous cell
carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in
OSF that are often not completely resected, causing local relapse. The aim of our
study was to find candidate protein biomarkers to detect OSF and predict
prognosis in BSCCs by quantitative proteomics approaches. METHODS: We compared
normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative
proteomics using isobaric tags for relative and absolute quantification (iTRAQ)
to discover proteins with differential expression. Gene Ontology and KEGG
networks were analyzed. The prognostic value of biomarkers was evaluated in 94
BSCCs accompanied with OSF. Significant associations were assessed by Kaplan
Meier survival and Cox-proportional hazards analysis. RESULTS: In total 30
proteins were identified with significantly different expression (false discovery
rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4
and FLNA, were validated. The disease-free survival was negatively associated
with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio,
2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs.
CONCLUSION: The present study indicates that iTRAQ quantitative proteomics
analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up
regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC
prognosis but also potential targets for its therapy.
PMID- 27485546
TI - Recurrent Brown's Syndrome after Superior Oblique Tendon Recession Treated by
Silicone Spacer.
AB - INTRODUCTION: Undercorrections have been reported after a number of surgical
procedures for Brown's syndrome. The reason for late undercorrections is not
clear but may be related to the heterogeneous etiology of Brown's syndrome.
PURPOSE: We report a patient with late undercorrection after superior oblique
tendon recession for Brown's syndrome that was partially relieved by a silicone
spacer placed nasally. RESULTS: We noted on surgical exploration that the
superior oblique tendon had attached to the sclera under the nasal border of the
superior rectus. Further weakening of the tendon was achieved by a No. 240 band
expander that resulted in improvement of adduction in elevation. CONCLUSION:
Undercorrections following surgery for Brown's syndrome can be relieved by
further weakening the superior oblique muscle. However, as late undercorrections
have been reported, the optimal timing of surgery is not certain.
PMID- 27485547
TI - Mitochondrial Ca2+ handling in Huntington's and Alzheimer's diseases - Role of ER
mitochondria crosstalk.
AB - Mitochondria play a relevant role in Ca2+ buffering, governing energy metabolism
and neuronal function. Huntington's disease (HD) and Alzheimer's disease (AD) are
two neurodegenerative disorders that, although clinically distinct, share
pathological features linked to selective brain damage. These include
mitochondrial dysfunction, intracellular Ca2+ deregulation and mitochondrial Ca2+
handling deficits. Both diseases are associated with misfolding and aggregation
of specific proteins that physically interact with mitochondria and interfere
with endoplasmic reticulum (ER)/mitochondria-contact sites. Cumulating evidences
indicate that impairment of mitochondrial Ca2+ homeostasis underlies the
susceptibility to selective neuronal death observed in HD and AD; however data
obtained with different models and experimental approaches are not always
consistent. In this review, we explore the recent literature on deregulation of
mitochondrial Ca2+ handling underlying the interplay between mitochondria and ER
in HD and AD-associated neurodegeneration.
PMID- 27485548
TI - Bronchial colonization and complications after lung cancer surgery.
AB - PURPOSE: Infectious complications occur following pulmonary resections preceded
or not by induction chemoradiotherapy. We aimed to investigate whether bacterial
colonization of the bronchial tree at the time of surgery was associated with
postoperative complications. PATIENTS AND METHODS: A retrospective analysis of
all patients who underwent open anatomical pulmonary resections for malignancies
at a single center was performed. Demographical data of the included patients,
intraoperative data, and data on the postoperative course of patients were
collected. Outcome of patients with a positive intraoperative bronchial culture
was compared to patients with a negative bronchial culture. Relations between the
presence of potential bacterial pathogens in the bronchial tree and other
possible risk factors for the development of postoperative infectious and non
infectious complications, were analyzed using uni- and multivariate analysis.
RESULTS: Between January 2010 and January 2012, a total of 121 consecutive
patients underwent open anatomical pulmonary resections for malignancy, of whom
45 were preceded by induction chemoradiotherapy and 5 by induction chemotherapy.
Intraoperative bronchial cultures were taken from 58 patients (48 %). Patients
with a positive bronchial culture developed significantly more infectious (88 %
vs. 20 %, p < 0.001) and non-infectious complications (63 % vs. 12 %, p = 0.001).
Positive intraoperative bronchial cultures showed the strongest association with
the development of infectious and non-infectious postoperative complications (OR
24.8 and 12.2, respectively). After multivariate analysis, only BMI less than 20
kg/m(2) and the presence of a positive intraoperative bronchial culture were
found to be independent risk factors for the development of infectious
complications. Chemoradiotherapy was not associated with postoperative
complications in the present study. CONCLUSIONS: Bacterial colonization of the
bronchial tree assessed intraoperatively, appears to be associated with higher
rates of infectious and non-infectious complications after pulmonary resection.
Whether early starting of appropriate antibiotics based on intraoperative-taken
culture findings will reduce the infectious complication rate in a subcategory of
patients needs to be investigated.
PMID- 27485550
TI - Theoretical investigation of the broad one-photon absorption line-shape of a
flexible symmetric carbazole derivative.
AB - The one-photon absorption spectrum of a carbazole derivative has been studied by
employing density functional response theory combined with a mixed
quantum/classical (QC) approach to simulate the spectral shape. In a first step
of our analysis we employed the vertical gradient (VG) vibronic model to
investigate the role of Franck-Condon (FC) profiles of the first ten electronic
excited states of the system, underlying most of the range of the experimental
spectrum. We then focussed on the first six excited states covering the low
energy region of the spectrum, and investigated the effect of inter-state
electronic couplings on the spectral shapes within Herzberg-Teller (HT) theory.
Furthermore, in order to introduce the broadening effects due to the two inter
ring torsions, we employed a QC approach, adopting VG vibronic models for high
frequency modes and computing the contribution of the torsions to the spectrum
from the distribution of the excitation energies along a two-dimensional relaxed
potential energy. Finally, we estimated the solvent inhomogeneous broadening by
computing the solvent reorganization energy using a polarizable continuum model.
Our calculations allow us to obtain a non-phenomenological description of the low
energy part of the spectrum in semi-quantitative agreement with experiment and to
dissect the relative importance of solvent, torsional flexibility, FC vibronic
progressions, and inter-state couplings in determining its broad spectral shapes
and the modulation of its intensity. Our analysis also clearly highlights that
the investigated carbazole represents a big challenge for available methodologies
due to the existence of many close-lying excited electronic states coupled by
internal low-frequency and high-frequency motions and by solvent fluctuations.
The study of their impact on the spectra at the HT level is only approximate and
more refined treatments would require a fully quantum-dynamical calculation on
the manifold of the coupled states.
PMID- 27485549
TI - Role of frailty and nutritional status in predicting complications following
total gastrectomy with D2 lymphadenectomy in patients with gastric cancer: a
prospective study.
AB - PURPOSE: This study was performed to determine the association of frailty and
nutritional status with postoperative complications after total gastrectomy (TG)
with D2 lymphadenectomy in patients with gastric cancer. METHODS: Patients
undergoing TG with D2 lymphadenectomy for gastric cancer between August 2014 and
February 2016 were enrolled. Frailty was evaluated by sarcopenia which was
diagnosed by a combination of third lumbar vertebra muscle index (L3 MI),
handgrip strength, and 6-m usual gait speed. Nutritional status was evaluated by
the nutritional risk screening 2002 (NRS 2002) score. Univariate and multivariate
analyses evaluating the risk factors for postoperative complications were
performed. RESULTS: A total of 158 patients were analyzed, and 27.2 % developed
complications within 30 days of surgery. One patient died within 30 days of the
operation. In the univariate analyses, NRS 2002 score >=3 (OR = 2.468, P =
0.012), sarcopenia (OR = 2.764, P = 0.008), and tumor located at the cardia (OR =
2.072, P = 0.046) were associated with the postoperative complications.
Multivariable analysis revealed that sarcopenia (OR = 3.084, P = 0.005) and tumor
located at the cardia (OR = 2.347, P = 0.026) were independent predictors of
postoperative complications. CONCLUSIONS: This study showed a significant
relationship between postoperative complications and geriatric frailty using
sarcopenia in patients with gastric cancer after TG with D2 lymphadenectomy.
Frailty should be integrated into preoperative risk assessment and may have
implications in preoperative decisionmaking.
PMID- 27485551
TI - Detection of selected periodontal bacteria in preschool children affected by
early childhood caries.
AB - The aim of this study was to compare the detection frequency of periodontal
bacteria in dental plaque in children with early childhood caries (ECC) with and
without gingival inflammation. A convenience sample of 25 preschool children
(mean age 3.61 years, SD 1.42) was recruited. Dental plaque was taken from
periodontal areas with and without visible signs of inflammation and processed
using the StomaGene(r) (Protean s.r.o. Czech Republic) and ParoCheck(r) 20
(Greiner Bio-one GmbH, Germany) detection kits. The two sample t tests between
percents for differences between inflammatory and healthy sites and kappa
statistics for the agreement of both systems were used. At the inflammatory
sites, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were
significantly more frequently detected by StomaGene(r) while Fusobacterium
nucleatum, A. actinomycetemcomitans, Tanarella forsythia and Prevotella
intermedia were significantly more frequently identified by ParoCheck(r) test.
The agreement between the two detection systems was substantial for A.
actinomycetemcomitans and F. nucleatum in the samples collected from inflamed
sites and only for F. nucleatum from clinically healthy sites. Therefore, we
recommend that the same system should be used when the same patient is examined
repeatedly.
PMID- 27485552
TI - Stochastic Induction of Long-Term Potentiation and Long-Term Depression.
AB - Long-term depression (LTD) and long-term potentiation (LTP) of granule-Purkinje
cell synapses are persistent synaptic alterations induced by high and low rises
of the intracellular calcium ion concentration ([Ca(2+)]), respectively. The
occurrence of LTD involves the activation of a positive feedback loop formed by
protein kinase C, phospholipase A2, and the extracellular signal-regulated
protein kinase pathway, and its expression comprises the reduction of the
population of synaptic AMPA receptors. Recently, a stochastic computational model
of these signalling processes demonstrated that, in single synapses, LTD is
probabilistic and bistable. Here, we expanded this model to simulate LTP, which
requires protein phosphatases and the increase in the population of synaptic AMPA
receptors. Our results indicated that, in single synapses, while LTD is bistable,
LTP is gradual. Ca(2+) induced both processes stochastically. The magnitudes of
the Ca(2+) signals and the states of the signalling network regulated the
likelihood of LTP and LTD and defined dynamic macroscopic Ca(2+) thresholds for
the synaptic modifications in populations of synapses according to an inverse
Bienenstock, Cooper and Munro (BCM) rule or a sigmoidal function. In conclusion,
our model presents a unifying mechanism that explains the macroscopic properties
of LTP and LTD from their dynamics in single synapses.
PMID- 27485553
TI - Aunting as a Call to Public Intellectualism: The Roles of (In)Visibility in
Health Communication Research and Service.
AB - In this essay, the author identifies the theme of (in)visibility permeating her
research on fathers of children with a rare genetic condition, Sturge-Weber
syndrome. The tension between physical visibility of the condition and lack of
awareness is explored, alongside issues of (in)visibility in coping and support
seeking strategies of fathers. Finally, the author examines her own experiences
in the research process through the lens of (in)visibility, in both managing her
own emotions and exploring her roles as a researcher, an aunt, and a public
intellectual.
PMID- 27485554
TI - Role of cysteine residues in the redox-regulated oligomerization and nucleotide
binding to EhRabX3.
AB - The enteric protozoan parasite, Entamoeba histolytica, an etiological agent of
amebiasis, is involved in the adhesion and destruction of human tissues.
Worldwide, the parasite causes about 50 million cases of amebiasis and 100,000
deaths annually. EhRabX3, a unique amoebic Rab GTPase with tandem G-domains,
possesses an unusually large number of cysteine residues in its N-terminal
domain. Crystal structure of EhRabX3 revealed an intra-molecular disulfide bond
between C39 and C163 which is critical for maintaining the 3-dimensional
architecture and biochemical function of this protein. The remaining six cysteine
residues were found to be surface exposed and predicted to be involved in inter
molecular disulfide bonds. In the current study, using biophysical and mutational
approaches, we have investigated the role of the cysteine residues in the
assembly of EhRabX3 oligomer. The self-association of EhRabX3 is found to be
redox sensitive, in vitro. Furthermore, the oligomeric conformation of EhRabX3
failed to bind and exchange the guanine nucleotide, indicating structural re
organization of the active site. Altogether, our results provide valuable
insights into the redox-dependent oligomerization of EhRabX3 and its implication
on nucleotide binding.
PMID- 27485555
TI - Transcription of the apicoplast genome.
AB - Many members of the Apicomplexa contain a remnant chloroplast, known as an
apicoplast. The apicoplast encodes numerous genes, and loss of the organelle is
lethal. Here, we present a summary of what is known about apicoplast
transcription. Unlike plant chloroplasts, there is a single RNA polymerase, and
initial transcription is polycistronic. RNA is then cleaved into tRNA, mRNA and
rRNA molecules. Significant levels of antisense transcription have been reported,
together with a single case of RNA editing. Polycistronic transcription is also
observed in the related algae Chromera and Vitrella, which retain a
photosynthetic chloroplast. Surprisingly, a polyU tail is added to Chromera and
Vitrella transcripts which encode proteins involved in photosynthesis. No such
tail is added to Plasmodium transcripts. Transcription in the Apicomplexa is
remarkably similar to that seen in the chloroplast of the related peridinin
dinoflagellate algae, reflecting the common evolutionary origins of the
organelle.
PMID- 27485556
TI - Schistosoma bovis-host interplay: Proteomics for knowing and acting.
AB - Schistosoma bovis is a parasite of ruminants that causes significant economic
losses to farmers throughout Africa, Southwestern Asia and the Mediterranean.
Additionally, recent studies have reported its zoonotic potential through the
formation of S. bovis*Schistosoma haematobium hybrids. As observed in the
Schistosoma species infecting humans, it is assumed that S. bovis has also
evolved host regulatory molecules that ensure its long-term survival in the
bloodstream of its host. Since these molecules could be potential targets for the
development of new drugs and anti-schistosome vaccines, their identification and
functional characterization were undertaken. With this aim in mind, the molecular
interface between S. bovis and its vertebrate host was subjected to a series of
proteomic studies, which started with the analysis of the proteomes of the S.
bovis moieties exposed to the host, namely, the excretory/secretory products and
the tegument surface. Thus, a wealth of novel molecular information of S. bovis
was obtained, which in turn allowed the identification of several parasite
proteins with fibrinolytic and anticoagulant activities that could be used by S.
bovis to regulate the host defensive systems. Following on, the host interface
was investigated by studying the proteome of the host vascular endothelium
surface at two points along the infection: in the lung vessels during the
schistosomula migration and in the portal vein after the parasites have reached
adulthood and sexual maturity. These studies have provided original data
regarding the proteomes of the endothelial cell surface of pulmonary vasculature
and portal vein in S. bovis-infected animals, and have shown significant changes
in these proteomes associated with infection. This review compiles current
information and the analyses of all the proteomic data from S. bovis and the S.
bovis-host interface, including the molecular and functional characterization of
S. bovis proteins that were found to participate in the regulation of the host
coagulation and fibrinolysis systems.
PMID- 27485557
TI - Order information in verbal working memory shifts the subjective midpoint in both
the line bisection and the landmark tasks.
AB - A largely substantiated view in the domain of working memory is that the
maintenance of serial order is achieved by generating associations of each item
with an independent representation of its position, so-called position markers.
Recent studies reported that the ordinal position of an item in verbal working
memory interacts with spatial processing. This suggests that position markers
might be spatial in nature. However, these interactions were so far observed in
tasks implying a clear binary categorization of space (i.e., with left and right
responses or targets). Such binary categorizations leave room for alternative
interpretations, such as congruency between non-spatial categorical codes for
ordinal position (e.g., begin and end) and spatial categorical codes for response
(e.g., left and right). Here we discard this interpretation by providing evidence
that this interaction can also be observed in a task that draws upon a continuous
processing of space, the line bisection task. Specifically, bisections are
modulated by ordinal position in verbal working memory, with lines bisected more
towards the right after retrieving items from the end compared to the beginning
of the memorized sequence. This supports the idea that position markers are
intrinsically spatial in nature.
PMID- 27485558
TI - Diverging P waves after convergent procedures: What do they mean?
PMID- 27485559
TI - Change in P wave morphology after convergent atrial fibrillation ablation.
AB - Convergent atrial fibrillation ablation involves extensive epicardial as well as
endocardial ablation of the left atrium. We examined whether it changes the
morphology of the surface P wave. We reviewed electrocardiograms of 29 patients
who underwent convergent ablation for atrial fibrillation. In leads V1, II and
III, we measured P wave duration, area and amplitude before ablation, and at 1, 3
and 6 months from ablation. After ablation, there were no significant changes in
P wave amplitude, area, or duration in leads II and III. There was a significant
reduction in the area of the terminal negative deflection of the P wave in V1
from 0.38 mm(2) to 0.13 mm(2) (p = 0.03). There is also an acute increase in the
amplitude and duration of the positive component of the P wave in V1 followed by
a reduction in both by 6 months. Before ablation, 62.5% of the patients had
biphasic P waves in V1. In 6 months, only 39.2% of them had biphasic P waves.
Hybrid ablation causes a reduction of the terminal negative deflection of the P
wave in V1 as well as temporal changes in the duration and amplitude of the
positive component of the P wave in V1. This likely reflects the reduced
electrical contribution of the posterior left atrium after ablation as well as
anatomical and autonomic remodeling. Recognition of this altered sinus P wave
morphology is useful in the diagnosis of atrial arrhythmias in this patient
population.
PMID- 27485560
TI - Phenotype guided characterization and molecular analysis of Indian patients with
long QT syndromes.
AB - BACKGROUND: Long QT syndromes (LQTS) are characterized by prolonged QTc interval
on electrocardiogram (ECG) and manifest with syncope, seizures or sudden cardiac
death. Long QT 1-3 constitute about 75% of all inherited LQTS. We classified a
cohort of Indian patients for the common LQTS based on T wave morphology and
triggering factors to prioritize the gene to be tested. We sought to identify the
causative mutations and mutation spectrum, perform genotype-phenotype correlation
and screen family members. METHODS: Thirty patients who fulfilled the criteria
were enrolled. The most probable candidate gene among KCNQ1, KCNH2 and SCN5A were
sequenced. RESULTS: Of the 30 patients, 22 were classified at LQT1, two as LQT2
and six as LQT3. Mutations in KCNQ1 were identified in 17 (77%) of 22 LQT1
patients, KCNH2 mutation in one of two LQT2 and SCN5A mutations in two of six
LQT3 patients. We correlated the presence of the specific ECG morphology in all
mutation positive cases. Eight mutations in KCNQ1 and one in SCN5A were novel and
predicted to be pathogenic by in-silico analysis. Of all parents with
heterozygous mutations, 24 (92%) of 26 were asymptomatic. Ten available siblings
of nine probands were screened and three were homozygous and symptomatic, five
heterozygous and asymptomatic. CONCLUSIONS: This study in a cohort of Asian
Indian patients highlights the mutation spectrum of common Long QT syndromes. The
clinical utility for prevention of unexplained sudden cardiac deaths is an
important sequel to identification of the mutation in at-risk family members.
PMID- 27485562
TI - Extreme bradycardia and transient asystole after massive gastric air entrapment.
PMID- 27485563
TI - Deceptive intracardiac electrograms during an ICD interrogation. A clinical
challenge.
AB - We present a case of a patient with significant structural heart disease from
previous cardiac surgeries who presented for an electrophysiology study and
radiofrequency ablation. The case highlights the significance of intra-atrial
conduction delays in such patients and potential pitfalls it can present while
interpreting intra-cardiac electrograms especially during implantable
cardioverter defibrillator (ICD) interrogations.
PMID- 27485561
TI - Ventricular pacing - Electromechanical consequences and valvular function.
AB - Although great strides have been made in the areas of ventricular pacing, it is
still appreciated that dyssynchrony can be malignant, and that appropriately
placed pacing leads may ameliorate mechanical dyssynchrony. However, the unknowns
at present include: 1. The mechanisms by which ventricular pacing itself can
induce dyssynchrony; 2. Whether or not various pacing locations can decrease the
deleterious effects caused by ventricular pacing; 3. The impact of novel methods
of pacing, such as atrioventricular septal, lead-less, and far-field surface
stimulation; 4. The utility of ECG and echocardiography in predicting response to
therapy and/or development of dyssynchrony in the setting of cardiac
resynchronization therapy (CRT) lead placement; 5. The impact of ventricular
pacing-induced dyssynchrony on valvular function, and how lead position
correlates to potential improvement. This review examines the existing literature
to put these issues into context, to provide a basis for understanding how
electrical, mechanical, and functional aspects of the heart can be distorted with
ventricular pacing. We highlight the central role of the mitral valve and its
function as it relates to pacing strategies, especially in the setting of CRT. We
also provide future directions for improved pacing modalities via alternative
pacing sites and speculate over mechanisms on how lead position may affect the
critical function of the mitral valve and thus overall efficacy of CRT.
PMID- 27485564
TI - Incessant tachycardia in a patient with advanced heart failure and left
ventricular assist device: What is the mechanism?
AB - We present a case of incessant wide-complex tachycardia in a patient with left
ventricular assist device, and discuss the differential diagnosis with an in
depth analysis of the intracardiac tracings during the invasive
electrophysiologic study, including interpretation of the relative timing of the
fascicular signals during tachycardia and in sinus rhythm, and interpretation of
pacing and entrainment maneuvers.
PMID- 27485565
TI - Use of a novel pacing mode to achieve biventricular pacing in a patient with
recurrent atrial lead dislodgement after CRT-D implantation.
AB - Cardiac resynchronization therapy device (CRT-P and CRT-D) implantation has
increased tremendously with increasing operator experience, eligible patients and
expansion of indications. Refinements in devices and algorithms now aid
physicians to improve biventricular pacing and optimize CRT. We report a case in
which an interesting device program was used to achieve biventricular pacing
after repeated dislodgement of the atrial lead in a patient implanted with CRT-D.
PMID- 27485566
TI - Development of Monopole Interaction Models for Ionic Compounds. Part I:
Estimation of Aqueous Henry's Law Constants for Ions and Gas Phase pKa Values for
Acidic Compounds.
AB - The SPARC (SPARC Performs Automated Reasoning in Chemistry) physicochemical
mechanistic models for neutral compounds have been extended to estimate Henry's
Law Constant (HLC) for charged species by incorporating ionic electrostatic
interaction models. Combinations of absolute aqueous pKa values, relative pKa
values in the gas phase, and aqueous HLC for neutral compounds have been used to
develop monopole interaction models that quantify the energy differences upon
moving an ionic solute molecule from the gas phase to the liquid phase. Inter
molecular interaction energies were factored into mechanistic contributions of
monopoles with polarizability, dipole, H-bonding, and resonance. The monopole
ionic models were validated by a wide range of measured gas phase pKa data for
450 acidic compounds. The RMS deviation error and R(2) for the ?OH, ?SH, ?CO2 H,
?CH3 and ?NR2 acidic reaction centers (C) were 16.9 kcal/mol and 0.87,
respectively. The calculated HLCs of ions were compared to the HLCs of 142 ions
calculated by quantum mechanics. Effects of inter-molecular interaction of the
monopoles with polarizability, dipole, H-bonding, and resonance on acidity of the
solutes in the gas phase are discussed.
PMID- 27485567
TI - The Complexation of the Anticancer Drug ThioTEPA with Methylated DNA Base
Guanine: Combined Ab Initio and QTAIM Investigation.
AB - Non-covalent complexes of methylated nitrogenous DNA base guanine (m(9) Gua) with
1 to 6 molecules of anticancer drug ThioTEPA (1,1',1''
phosphorothioyltriaziridine) have been investigated by molecular modeling
techniques (molecular docking and DFT geometry optimization), ab initio
wavefunction calculations and the quantum theory of atoms in molecules (QTAIM).
The accuracy of complex structures predicted by standard molecular docking
techniques have been assessed by comparing them with ab initio calculations, and
the most important differences have been discussed. Obtained stabilization
enthalpies (kcal/mol) for the m(9) Gua???(ThioTEPA)n complexes with n=1...6 have
been found to be -15.6, -26.5, -38.4, -49.6, -60.5 and -69.3 respectively. The
non-covalent interactions revealed by the QTAIM method have been shown to be a
dominating factor responsible for the complex stability, with hydrogen bonds of
NH???N type being the most important interactions in small (n=1 to 4) and CH???N
bonds - in large (n=5, 6) complexes. The obtained results may help to understand
ThioTEPA-DNA interactions and clarify the mechanism of the drug action.
PMID- 27485568
TI - Development of a New Decision Tree to Rapidly Screen Chemical Estrogenic
Activities of Xenopus laevis.
AB - During the last past decades, there is an increasing number of studies about
estrogenic activities of the environmental pollutants on amphibians and many
determination methods have been proposed. However, these determination methods
are time-consuming and expensive, and a rapid and simple method to screen and
test the chemicals for estrogenic activities to amphibians is therefore
imperative. Herein is proposed a new decision tree formulated not only with
physicochemical parameters but also a biological parameter that was successfully
used to screen estrogenic activities of the chemicals on amphibians. The
biological parameter, CDOCKER interaction energy (Ebinding ) between chemicals
and the target proteins was calculated based on the method of molecular docking,
and it was used to revise the decision tree formulated by Hong only with
physicochemical parameters for screening estrogenic activity of chemicals in rat.
According to the correlation between Ebinding of rat and Xenopus laevis, a new
decision tree for estrogenic activities in Xenopus laevis is finally proposed.
Then it was validated by using the randomly 8 chemicals which can be frequently
exposed to Xenopus laevis, and the agreement between the results from the new
decision tree and the ones from experiments is generally satisfactory.
Consequently, the new decision tree can be used to screen the estrogenic
activities of the chemicals, and combinational use of the Ebinding and classical
physicochemical parameters can greatly improves Hong's decision tree.
PMID- 27485569
TI - Pharmacophore Mapping, In Silico Screening and Molecular Docking to Identify
Selective Trypanosoma brucei Pteridine Reductase Inhibitors.
AB - Trypanosoma brucei Pteridine reductase (TbPTR1) is of vital importance and is an
established drug target for dreaded Human African trypanosomiasis (HAT).
Pharmacophore perception strategy has been employed to identify key chemical
features responsible for the biological activity for TbPTR1. The findings suggest
that three different pharmacophore features can be associated with T. brucei anti
PTR1 activity namely: H-bond donors (D), Hydrophobic aromatic (H) and Ring
aromatic (R). The resulting hypothesis is able to predict the activity of other
existing TbPTR1 inhibitors with a correlation coefficient (r) of 0.89. An in
silico database screening, based on the best hypothesis, has been used to
identify some potential nanomolar range TbPTR1 inhibitors. These compounds were
then checked by molecular docking and subjected to ADMET analysis. Further, a
detailed comparison of the pharmacophore behavior and differential analysis of
binding pockets of T. brucei and L. major was made which revealed subtle
differences in terms of their shape and charge properties. This investigation can
form the basis for tweaking the specificity of compounds for generating new
improved species specific inhibitor molecules for Pteridine reductase in these
different parasitic protozoans.
PMID- 27485570
TI - eFindSite: Enhanced Fingerprint-Based Virtual Screening Against Predicted Ligand
Binding Sites in Protein Models.
AB - A standard practice for lead identification in drug discovery is ligand virtual
screening, which utilizes computing technologies to detect small compounds that
likely bind to target proteins prior to experimental screens. A high accuracy is
often achieved when the target protein has a resolved crystal structure; however,
using protein models still renders significant challenges. Towards this goal, we
recently developed eFindSite that predicts ligand binding sites using a
collection of effective algorithms, including meta-threading, machine learning
and reliable confidence estimation systems. Here, we incorporate fingerprint
based virtual screening capabilities in eFindSite in addition to its flagship
role as a ligand binding pocket predictor. Virtual screening benchmarks using the
enhanced Directory of Useful Decoys demonstrate that eFindSite significantly
outperforms AutoDock Vina as assessed by several evaluation metrics. Importantly,
this holds true regardless of the quality of target protein structures. As a
first genome-wide application of eFindSite, we conduct large-scale virtual
screening of the entire proteome of Escherichia coli with encouraging results. In
the new approach to fingerprint-based virtual screening using remote protein
homology, eFindSite demonstrates its compelling proficiency offering a high
ranking accuracy and low susceptibility to target structure deformations. The
enhanced version of eFindSite is freely available to the academic community at
http://www.brylinski.org/efindsite.
PMID- 27485571
TI - Easy Identification of Residues Involved on Structural Differences Between
Nonphosphorylated and Phosphorylated CDK2?Cyclin A Complexes Using Two
Dimensional Networks.
AB - The structures of proteins in Protein Data Bank (PDB) contain a lot of
information that can be revealed through the use of tools to facilitate their
organization and analysis. The increase in available structural data of
nonphosphorylated and phosphorylated CDK2?cyclin A (npCDK2?cycA and pCDK2?cycA)
complexes has enabled a more realistic description of the fine structural details
of the interface residues of these proteins. This work reports the application of
two-dimensional network representations (TDNRs) to the structures deposited in
PDB to distinguish the differences in the surface between both complexes due to
phosphorylation. As a result, a detailed map of the hydrogen bonds (HBs) and
hydrophobic interactions between the T-loop residues of CDK2 and the residues of
cycA that are different among nonphosphorylated and phosphorylated complexes were
described. In addition, we found some interesting subtle differences in the
CDK2?cycA interface between nonphosphorylated and phosphorylated complexes due to
residues that are not located at the T-loop of CDK2. We noted that some HB
interactions in CDK2?cycA complex are reinforced when the CDK2 is phosphorylated.
PMID- 27485572
TI - A case of recurrent swimming-induced pulmonary edema in a triathlete: the need
for awareness.
AB - This report discusses a rare case of a 55-year-old female triathlete who
developed recurrent episodes of swimming-induced pulmonary edema (SIPE). She had
two hospital admissions with pulmonary edema after developing breathlessness
while swimming, including a near-drowning experience in an open water swim. With
increasing popularity of triathlon and open water sports, this case highlights
the importance of a greater awareness of SIPE among health professionals, event
organizers, and athletes. This report explores the previous reported cases in
triathletes and those who have suffered recurrent episodes. It is paramount that
an accurate diagnosis is made as these individuals may be at an increased risk of
future life-threatening episodes.
PMID- 27485573
TI - Microchemical Study of Pigments and Binders in Polychrome Relics from Maiji
Mountain Grottoes in Northwestern China.
AB - In this study, an integrated analytical method was developed to investigate the
composition of both the inorganic pigments and organic binders of polychrome
relics in Maiji Mountain Grottoes in northwestern China. Cross-sections of each
sample were prepared at the beginning of the study, and all experiments were
carried out on these cross-sections. Polychromic structures were revealed by
optical microscopy and scanning electron microscopy-backscattered electron
imaging. Inorganic materials were determined by using SEM coupled with an energy
dispersive spectrometer and MU-Raman spectrometer, whereas organic materials were
identified by staining techniques and highly sensitive and specific
immunofluorescence microscopy. Data showed that the red colors are attributed to
one or two pigments of red ochre, cinnabar, and minium; the blue pigment is
natural lazurite; the green pigment is ascribed to atacamite; the white color is
attributed to potassium feldspar; and the black surface is formed by the
discoloration of minium to plattnerite under the influence of environmental
factors. Regarding organic binders used in painting and preparation layers,
mammalian animal glue and chicken egg white were both found alone or in mixture.
Finally, the conclusion is made that the Secco technique is employed in
polychrome relics from Maiji Mountain Grottoes.
PMID- 27485574
TI - Enhancing the quality of oral nutrition support for hospitalized patients: a
mixed methods knowledge translation study (The EQONS study).
AB - AIM: The aim of this study was to report a multifaceted knowledge translation
intervention to facilitate use of the Malnutrition Universal Screening Tool and
innovation in nutritional care for patients at risk of malnutrition. BACKGROUND:
Malnutrition among hospitalized patients is a widespread problem leading to
adverse health outcomes. Despite evidence of the benefits of malnutrition
screening and recommendations for achieving good nutrition, shortfalls in
practice continue. DESIGN: A mixed method integrated knowledge translation study.
METHODS: The knowledge translation intervention comprised nutrition champions
supported by knowledge translation facilitators and an action planning process.
Data collection was undertaken over 18 months between 2011-2012 in a hospital in
England. Data comprised observation of mealtimes, audit of patient records,
survey of nurses and semi-structured interviews with nutrition champions,
knowledge translation facilitators, senior ward nurses and nurse managers.
FINDINGS: Statistically significant relationships (Chi Square) were observed
between self-reported confidence of nurses (a) to assess patients using the
Malnutrition Universal Screening Tool, (b) to teach colleagues how to use the
Malnutrition Universal Screening Tool and (c) to ensure that patients were
assessed within 24 hours of admission. Ward-based nutrition champions facilitated
successful innovation in nutrition support. Contextual factors operating at micro
(ward), meso (organization) and macro (healthcare system) levels acted as
barriers and enablers for change. CONCLUSION: Nutrition champions were successful
in increasing the timely assessment of patients at risk of malnutrition and
promoting innovation in nutritional care. Support from knowledge translation
facilitators helped nutrition champions develop their role and work
collaboratively with senior ward nurses to implement action plans for improving
nutrition.
PMID- 27485576
TI - Do we need intracardiac echo to guide ablation of ventricular arrhythmias from
the papillary muscles?
PMID- 27485575
TI - Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of
Interactions with Different Types of Acetylcholine Receptors.
AB - Human-secreted Ly-6/uPAR-related protein-2 (SLURP-2) regulates the growth and
differentiation of epithelial cells. Previously, the auto/paracrine activity of
SLURP-2 was considered to be mediated via its interaction with the alpha3beta2
subtype of the nicotinic acetylcholine receptors (nAChRs). Here, we describe the
structure and pharmacology of a recombinant analogue of SLURP-2. Nuclear magnetic
resonance spectroscopy revealed a 'three-finger' fold of SLURP-2 with a conserved
beta-structural core and three protruding loops. Affinity purification using
cortical extracts revealed that SLURP-2 could interact with the alpha3, alpha4,
alpha5, alpha7, beta2, and beta4 nAChR subunits, revealing its broader
pharmacological profile. SLURP-2 inhibits acetylcholine-evoked currents at
alpha4beta2 and alpha3beta2-nAChRs (IC50 ~0.17 and >3 MUM, respectively)
expressed in Xenopus oocytes. In contrast, at alpha7-nAChRs, SLURP-2
significantly enhances acetylcholine-evoked currents at concentrations <1 MUM but
induces inhibition at higher concentrations. SLURP-2 allosterically interacts
with human M1 and M3 muscarinic acetylcholine receptors (mAChRs) that are
overexpressed in CHO cells. SLURP-2 was found to promote the proliferation of
human oral keratinocytes via interactions with alpha3beta2-nAChRs, while it
inhibited cell growth via alpha7-nAChRs. SLURP-2/mAChRs interactions are also
probably involved in the control of keratinocyte growth. Computer modeling
revealed possible SLURP-2 binding to the 'classical' orthosteric
agonist/antagonist binding sites at alpha7 and alpha3beta2-nAChRs.
PMID- 27485577
TI - Different impact of long-detection interval and anti-tachycardia pacing in
reducing unnecessary shocks: data from the ADVANCE III trial.
AB - AIMS: A long-detection interval (LDI) (30/40 intervals) has been proved to be
superior to a standard-detection interval (SDI) (18/24 intervals) in terms of
reducing unnecessary implantable cardioverter defibrillator (ICD) therapies. To
better evaluate the different impact of LDI and anti-tachycardia pacing (ATP) on
reducing painful shocks, we assessed all treated episodes in the ADVANCE III
trial. METHODS AND RESULTS: A total of 452 fast (200 ms < cycle length <= 320 ms)
arrhythmic episodes were recorded: 284 in 138 patients in the SDI arm and 168 in
82 patients in the LDI arm (106/452 inappropriate detections). A total of 346
fast ventricular tachycardias (FVT) were detected in 169 patients: 208 in 105
patients with SDI and 138 in 64 patients with LDI. Setting LDI determined a
significant reduction in appropriate but unnecessary therapies [208 in SDI vs.
138 in LDI; incidence rate ratio (IRR): 0.61 (95% CI 0.45-0.83), P = 0.002]. Anti
tachycardia pacing determined another 52% reduction in unnecessary shocks [208 in
SDI with hypothetical shock-only programming vs. 66 in LDI with ATP; IRR: 0.37
(95% CI 0.25-0.53, P < 0.001)]. The efficacy of ATP in terminating FVT was 63% in
SDI and 52% in LDI (P = 0.022). No difference in the safety profile
(acceleration/degeneration and death/cardiovascular hospitalizations) was
observed between the two groups. CONCLUSION: The combination of LDI and ATP
during charging is extremely effective and significantly reduces appropriate but
unnecessary therapies. The use of LDI alone yielded a 39% reduction in
appropriate but unnecessary therapies; ATP on top of LDI determined another 52%
reduction in unnecessary shocks. The strategy of associating ATP and LDI could be
considered in the majority of ICD recipients.
PMID- 27485578
TI - Intracardiac echo-facilitated 3D electroanatomical mapping of ventricular
arrhythmias from the papillary muscles: assessing the 'fourth dimension' during
ablation.
AB - AIMS: Ventricular arrhythmias (VA) originating from a papillary muscle (PM) have
recently been described as a distinct clinical entity with peculiar features that
make its treatment with catheter ablation challenging. Here, we report our
experience using an intracardiac echo-facilitated 3D electroanatomical mapping
approach in a case series of patients undergoing ablation for PM VA. METHODS AND
RESULTS: Sixteen patients who underwent catheter ablation for ventricular
tachycardia (VT) or symptomatic premature ventricular contractions originating
from left ventricular PMs were included in the study. A total of 24 procedures
(mean 1.5 per patient) were performed: 15 using a retrograde aortic approach and
9 using a transseptal approach. Integrated intracardiac ultrasound for 3D
electroanatomical mapping was used in 15 of the 24 procedures. The posteromedial
PM was the most frequent culprit for the clinical arrhythmia, and the body was
the part of the PM most likely to be the successful site for ablation. The site
of ablation was identified based on the best pace map matching the clinical
arrhythmia and the site of earliest the activation. At a mean follow-up of 10.5
+/- 7 months, only two patients had recurrent arrhythmias following a repeat
ablation procedure. CONCLUSION: An echo-facilitated 3D electroanatomical mapping
allows for real-time creation of precise geometries of cardiac chambers and
endocavitary structures. This is useful during procedures such as catheter
ablation of VAs originating from PMs, which require detailed representation of
anatomical landmarks. Routine adoption of this technique should be considered to
improve outcomes of PM VA ablation.
PMID- 27485579
TI - Template-Directed Synthesis of Porous and Protective Core-Shell Bionanoparticles.
AB - Metal-organic frameworks (MOFs) are promising high surface area coordination
polymers with tunable pore structures and functionality; however, a lack of good
size and morphological control over the as-prepared MOFs has persisted as an
issue in their application. Herein, we show how a robust protein template,
tobacco mosaic virus (TMV), can be used to regulate the size and shape of as
fabricated MOF materials. We were able to obtain discrete rod-shaped TMV@MOF core
shell hybrids with good uniformity, and their diameters could be tuned by
adjusting the synthetic conditions, which can also significantly impact the
stability of the core-shell composite. More interestingly, the virus particle
underneath the MOF shell can be chemically modified using a standard
bioconjugation reaction, showing mass transportation within the MOF shell.
PMID- 27485580
TI - Keep nanotechnology in mind.
PMID- 27485581
TI - Correction.
PMID- 27485582
TI - Hopes and anxieties.
PMID- 27485584
TI - Origin and control of blinking in quantum dots.
AB - Semiconductor nanocrystals offer an enormous diversity of potential device
applications, based on their size-tunable photoluminescence, high optical
stability and 'bottom-up' chemical approaches to self-assembly. However, the
promise of such applications can be seriously limited by photoluminescence
intermittency in nanocrystal emission, that is, 'blinking', arising from the
escape of either one or both of the photoexcited carriers to the nanocrystal
surface. In the first scenario, the remaining nanocrystal charge quenches
photoluminescence via non-radiative Auger recombination, whereas for the other,
the exciton is thought to be intercepted before thermalization and does not
contribute to the photoluminescence. This Review summarizes the current
understanding of the mechanisms responsible for nanocrystal blinking kinetics as
well as core-shell engineering efforts to control such phenomena. In particular,
'softening' of the core-shell confinement potential strongly suppresses non
radiative Auger processes in charged nanocrystals, with successful non-blinking
implementations demonstrated in CdSe-CdS core-thick-shell nanocrystals and their
modifications.
PMID- 27485585
TI - Erratum: Additive interfacial chiral interaction in multilayers for stabilization
of small individual skyrmions at room temperature.
PMID- 27485586
TI - A tale of two disciplines.
PMID- 27485587
TI - Re: Prediction of adverse perinatal outcome of small-for-gestational-age
pregnancy using size centiles and conditional growth centiles. H. O. Karlsen, S.
L. Johnsen, S. Rasmussen and T. Kiserud. Ultrasound Obstet Gynecol 2016; 48: 217
223.
PMID- 27485588
TI - Re: Warping of the levator hiatus: how significant is it? H. P. Dietz, I.
Severino, I. Kamisan Atan, K. L. Shek and R. Guzman Rojas. Ultrasound Obstet
Gynecol 2016; 48: 239-242.
PMID- 27485589
TI - ISUOG Practice Guidelines: invasive procedures for prenatal diagnosis.
PMID- 27485590
TI - Repeated Hospital Transfers and Associated Outcomes by Residency Time Among
Nursing Home Residents in Taiwan.
AB - BACKGROUND: Nursing home residents' repeated transfers to hospital are costly and
can lead to in-hospital complications and high mortality for frail residents.
However, no research has examined the trajectory of residents' symptoms over
their nursing home residency and its relationship to hospital transfer. AIM: The
purpose of this retrospective chart-review study was to examine associations
between nursing home residents' characteristics, including length of residency,
and repeated hospital transfers as well as the trajectory of transfers during
residency. DESIGN: For this retrospective study, we reviewed 583 residents'
charts in 6 randomly selected nursing homes from northern Taiwan. Data were
analyzed by descriptive statistics, chi-squared tests, and 1-way analysis of
variance. RESULTS: About half of nursing home residents who had been transferred
to hospital (n = 320) were transferred more than twice during their residency
(50.97%). Residents who had been transferred 1, 2, 3, or >=4 times differed
significantly in length of residency (F = 3.85, P = .01), physical status (F =
2.65, P = .05), medical history of pneumonia (chi2 = 13.03, P = .01), and
fractures (chi2 = 8.52, P = .04). Residents with different numbers of transfers
differed significantly in their reasons for transfer, that is, falls (chi2 =
13.01, P = .01) and tube problems (chi2 = 8.87, P = .03). Among 705 total
transfers, fever was the top reason for transfer, and transfer prevalence
increased with nursing home residency. CONCLUSION: To decrease the chance of
residents' hospital transfer, nursing home staff should be educated about
recognizing and managing fever symptoms, infection-control programs such as
influenza vaccination should be initiated, and fall-prevention/education programs
should be started when residents first relocate to nursing homes.
PMID- 27485591
TI - Intensity of Occupational Therapy Utilization in Nursing Home Residents: The Role
of Sensory Impairments.
AB - OBJECTIVES: Unaddressed functional limitations in nursing home (NH) residents can
lead to unnecessary, excess disability that negatively affects residents' quality
of life. In order to enhance functioning, NH residents can receive rehabilitation
such as occupational therapy (OT). However, little is known about factors that
may aid or hinder full therapy utilization in NH residents. Hence, our study
investigated sensory impairments (vision and hearing) and other important health
related variables (eg, cognitive functioning) as predictors of intensity of OT
utilization. DESIGN: Retrospective study with data extraction from electronic
medical records (EMRs). SETTING: Skilled nursing facility. PARTICIPANTS: A sample
of newly admitted NH residents (N = 121). MEASUREMENTS: Single items for
sociodemographic variables and clinician-rated extent of sensory difficulties
(hearing and vision) as well as pain presence based on Minimum Data Set (MDS 3.0)
assessments in EMRs. MDS 3.0 scales assess cognitive functioning, depressive
symptoms, and functional dependency. Total hours of OT received during 90 days
postadmission to the NH were extracted from the EMRs. RESULTS: A regression
analysis demonstrated that better admission hearing and cognitive functioning,
fewer admission depressive symptoms, and higher admission functional dependence
were associated with more intense OT utilization-more hours used-over a 90-day
period. CONCLUSION: This study emphasizes the importance of assessing and
addressing hearing difficulties and depression in NH residents in order to
optimize utilization of beneficial OT services and to promote most optimal
independent functioning and quality of life.
PMID- 27485592
TI - Novel polymorphic microsatellite loci for distinguishing rock bass (Ambloplites
rupestris), Roanoke bass (Ambloplites cavifrons), and their hybrids.
AB - The rock bass (Ambloplites rupestris) is a popular sport-fish native to the
Mississippi and Great Lakes basins of North America. The species has been widely
introduced outside its native range, including into Atlantic-slope streams of
Virginia where it may hybridize with an imperiled, similar-looking congener, the
Roanoke bass (Ambloplites cavifrons). In this study, we identified and evaluated
novel molecular markers to facilitate identification of these species and study
the extent of hybridization. Using molecular libraries developed from A.
rupestris, we identified a suite of candidate nuclear microsatellite loci,
synthesized primer sets, and tested these markers for amplification and
polymorphism in populations of both species. We then calculated standard
diversity statistics within and differentiation statistics between species, the
latter providing an indication of marker power for distinguishing the species and
their hybrids. Additionally, we evaluated our efficiency for identifying hybrids
by classifying simulated genotypes of known ancestry. Eleven loci were
polymorphic (2-22 alleles per locus) and reliably amplified in both species.
Multilocus genetic differentiation between A. cavifrons and A. rupestris was
quite high (F ST = 0.66; D LR = 19.3), indicating the high statistical power of
this marker set for species and hybrid identification. Analyses of simulated data
suggested these markers reliably distinguish between hybrids and non-hybrids, as
well as between F1 hybrids and backcrossed individuals. This panel of 11 loci
should prove useful for understanding patterns of hybridization between A.
rupestris and A. cavifrons. As the first microsatellite markers developed for
Ambloplites, these markers also should prove broadly useful for population
genetic studies of this genus.
PMID- 27485595
TI - Minimax and admissible adaptive two-stage designs in phase II clinical trials.
AB - BACKGROUND: Simon's two-stage design is the most widely implemented among multi
stage designs in phase II clinical trials to assess the activity of a new
treatment in a single-arm study. In this two-stage design, the sample size from
the second stage is fixed regardless of the number of responses observed in the
first stage. METHODS: We develop a new minimax adaptive design for phase II
clinical trials, by using the branch-and-bound intelligent algorithm based on
conditional error functions. RESULTS: We compare the performance of the proposed
design and competitors, including Simon's minimax design, and a modified Simon's
design that allows early stopping for futility or efficacy. The maximum sample
size of the proposed minimax adaptive design is guaranteed to be less than or
equal to those from other existing designs. When the proposed design has the same
maximum sample size as others, it always has the smallest expected sample size.
In addition to the minimax adaptive design, we also introduce admissible adaptive
designs determined from a Bayesian perspective. CONCLUSIONS: The proposed
adaptive minimax design can save sample sizes for a clinical trial. The minimum
required sample size is critical to reduce the cost of a project.
PMID- 27485596
TI - Individualizing endpoints in randomized clinical trials to better inform
individual patient care: the TARGET proposal.
AB - In practice, critical care practitioners individualize treatments and goals of
care for each patient in light of that patient's acute and chronic
pathophysiology, as well as their beliefs and values. Yet critical care
researchers routinely measure one endpoint for all patients during randomized
clinical trials (RCTs), eschewing any such individualization. More recent
methodology work has explored the possibility that enrollment criteria in RCTs
can be individualized, as can data analysis plans. Here we propose that the
specific endpoints of a RCT can be individualized-that is, different patients
within a single RCT might have different secondary endpoints measured. If done
rigorously and objectively, based on pre-randomization data, such
individualization of endpoints may improve the bedside usefulness of information
obtained during a RCT, while perhaps also improving the power and efficiency of
any RCT. We discuss the theoretical underpinnings of this proposal in light of
related innovations in RCT design such as sliding dichotomies. We discuss what a
full elaboration of such individualization would require, and outline a pragmatic
initial step towards the use of "individualized secondary endpoints" in a large
RCT evaluating optimal enteral nutrition targets in the critically ill.
PMID- 27485597
TI - Methodological concerns related to response bias in migrant and seasonal
farmworkers.
AB - BACKGROUND: The original objective was to measure the impact of kneepads on
musculoskeletal pain in migrant and seasonal farmworkers (MSFWs). Secondary
analyses were conducted to quantify the extent to which response bias may have
skewed the study's results. METHODS: Surveys were used to collect data on
baseline pain and post-intervention pain, the amount of time participants spent
wearing kneepads, and their overall ratings of the intervention. RESULTS:
Participants did not experience significantly less pain with kneepads, and wore
them for considerably less than the prescribed amount of time. However, subjects
rated them very favorably. Given the strong suspicion of response bias, no firm
conclusions could be drawn regarding the intervention. CONCLUSIONS: Unique survey
methodologies must be used with MSFWs, who tend to have low research literacy and
are particularly susceptible to response bias. Objective study outcomes are
particularly favorable in this population in order to minimize dependence on self
reported measures. Am. J. Ind. Med. 59:1112-1119, 2016. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27485599
TI - Serum-based microRNA signatures in early diagnosis and prognosis prediction of
colon cancer.
AB - Early detection of colorectal cancer is the main prerequisite for successful
treatment and reduction of mortality. Circulating microRNAs were previously
identified as promising diagnostic, prognostic and predictive biomarkers. The
purpose of this study was to identify serum microRNAs enabling early diagnosis
and prognosis prediction of colon cancer. In total, serum samples from 427 colon
cancer patients and 276 healthy donors were included in three-phase biomarker
study. Large-scale microRNA expression profiling was performed using Illumina
small RNA sequencing. Diagnostic and prognostic potential of identified microRNAs
was validated on independent training and validation sets of samples using RT
qPCR. Fifty-four microRNAs were found to be significantly deregulated in serum of
colon cancer patients compared to healthy donors (P < 0.01). A diagnostic four
microRNA signature consisting of miR-23a-3p, miR-27a-3p, miR-142-5p and miR-376c
3p was established (AUC = 0.917), distinguishing colon cancer patients from
healthy donors with sensitivity of 89% and specificity of 81% (AUC = 0.922). This
panel of microRNAs exhibited high diagnostic performance also when analyzed
separately in colon cancer patients in early stages of the disease (T1-4N0M0; AUC
= 0.877). Further, a prognostic panel based on the expression of miR-23a-3p and
miR-376c-3p independent of TNM stage was established (HR 2.30; 95% CI 1.44-3.66;
P < 0.0004). In summary, highly sensitive signatures of circulating microRNAs
enabling non-invasive early detection and prognosis prediction of colon cancer
were identified.
PMID- 27485598
TI - Genetic variations in the Hippo signaling pathway and breast cancer risk in
African American women in the AMBER Consortium.
AB - The Hippo signaling pathway regulates cellular proliferation and survival, thus
exerting profound effects on normal cell fate and tumorigenesis. Dysfunction of
the Hippo pathway components has been linked with breast cancer stem cell
regulation, as well as breast tumor progression and metastasis. TAZ, a key
component of the Hippo pathway, is highly expressed in triple negative breast
cancer; however, the associations of genetic variations in this important pathway
with breast cancer risk remain largely unexplored. Here, we analyzed 8309
germline variants in 15 genes from the Hippo pathway with a total of 3663 cases
and 4687 controls from the African American Breast Cancer Epidemiology and Risk
Consortium. Odds ratios (ORs) were estimated using logistic regression for
overall breast cancer, by estrogen receptor (ER) status (1983 ER positive and
1098 ER negative), and for case-only analyses by ER status. The Hippo signaling
pathway was significantly associated with ER-negative breast cancer (pathway
level P = 0.02). Gene-based analyses revealed that CDH1 was responsible for the
pathway association (P < 0.01), with rs4783673 in CDH1 statistically significant
after gene-level adjustment for multiple comparisons (P = 9.2*10(-5), corrected P
= 0.02). rs142697907 in PTPN14 was associated with ER-positive breast cancer and
rs2456773 in CDK1 with ER-negativity in case-only analysis after gene-level
correction for multiple comparisons (corrected P < 0.05). In conclusion, common
genetic variations in the Hippo signaling pathway may contribute to both ER
negative and ER+ breast cancer risk in AA women.
PMID- 27485600
TI - Design, synthesis and anti-P. falciparum activity of pyrazolopyridine-sulfonamide
derivatives.
AB - Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group
to benzenesulfonamide moieties with different substituents in the 4-position were
synthesized and assayed against Plasmodium falciparum. These ten compounds
exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50
values ranging from 3.46 to 9.30MUM. The most active derivatives with substituent
R2=Cl or CH3 at the benzenesulfonamide moiety exhibited the lowest IC50.
Compounds with an R1=CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4
b]pyridine ring presented lower activity than those with a CN substituent. The 1H
pyrazolo[3,4-b]pyridine system appears to be promising for further studies as an
antimalarial for overcoming the burden of resistance in P. falciparum.
PMID- 27485601
TI - Identification of the minimum pharmacophore of lipid-phosphatidylserine (PS)
binding peptide-peptoid hybrid PPS1D1.
AB - We previously reported a unique peptide-peptoid hybrid, PPS1 that specifically
recognizes lipid-phosphatidylserine (PS) and a few other negatively charged
phospholipids, but not neutral phospholipids, on the cell membrane. The dimeric
version of PPS1, i.e., PPS1D1 triggers strong cancer cell cytotoxicity and has
been validated in lung cancer models both in vitro and in vivo. Given that PS and
other negatively charged phospholipids are abundant in almost all tumor
microenvironments, PPS1D1 is an attractive drug lead that can be developed into a
globally applicable anti-cancer agent. Therefore, it is extremely important to
identify the minimum pharmacophore of PPS1D1. In this study, we have synthesized
alanine/sarcosine derivatives as well as truncated derivatives of PPS1D1. We
performed ELISA-like competitive binding assay to evaluate the PS-recognition
potential and standard MTS cell viability assay on HCC4017 lung cancer cells to
validate the cell cytotoxicity effects of these derivatives. Our studies indicate
that positively charged residues at the second and third positions, as well as
four hydrophobic residues at the fifth through eighth positions, are imperative
for the binding and activity of PPS1D1. Methionine at the first position was not
essential, whereas the positively charged Nlys at the fourth position was
minimally needed, as two derivatives that were synthesized replacing this residue
were almost as active as PPS1D1.
PMID- 27485602
TI - Similarities and differences in affinity and binding modes of tricyclic pyrimido-
and pyrazinoxanthines at human and rat adenosine receptors.
AB - A new series of 32 pyrimido- and 5 tetrahydropyrazino[2,1-f]purinediones was
obtained and evaluated for their adenosine receptors (ARs) affinities. The 1,3
dibutyl derivative of 9-(4-(2-(dimethylamino)ethoxy)phenyl)-6,7,8,9
tetrahydropyrimido[1,2-f]purine-2,4(1H,3H)-dione was found to be the most potent
A1 AR antagonist of the present series, showing selectivity over the other AR
subtypes. The structure-activity for the obtained purinediones was established.
Docking experiments of the investigated library to homology models of the human
and rat A1 and A2A ARs allowed to compare the expected binding modes for selected
compounds. The detailed analysis of binding cavities within individual AR
subtypes indicated small but significant structural variations that may underlie
the observed differences in binding affinities of purinediones at particular
subtypes and species.
PMID- 27485604
TI - Blinded predictions of binding modes and energies of HSP90-alpha ligands for the
2015 D3R grand challenge.
AB - In the framework of the 2015 D3R inaugural grand challenge, blind binding pose
and affinity predictions were performed for a set of 180 ligands of the Heat
Shock Protein HSP90-alpha protein, a relevant cancer target. Spectral clustering
was used to rapidly identify alternative binding site conformations in publicly
available crystallographic HSP90-alpha structures. Subsequently, multiple docking
and scoring protocols employing the software Autodock Vina and rDock were applied
to predict binding modes and rank order ligands. Alchemical free energy
calculations were performed with the software FESetup and Sire/OpenMM to predict
binding affinities for three congeneric series subsets. Some of the protocols
used here were ranked among the top submissions according to most of the
evaluation metrics. Docking performance was excellent, but the scoring results
were disappointing. A critical assessment of the results is reported, as well as
suggestions for future similar competitions.
PMID- 27485603
TI - Computer-aided discovery of anti-HIV agents.
AB - A review is provided on efforts in our laboratory over the last decade to
discover anti-HIV agents. The work has focused on computer-aided design and
synthesis of non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs)
with collaborative efforts on biological assaying and protein crystallography.
Numerous design issues were successfully addressed including the need for potency
against a wide range of viral variants, good aqueous solubility, and avoidance of
electrophilic substructures. Computational methods including docking, de novo
design, and free-energy perturbation (FEP) calculations made essential
contributions. The result is novel NNRTIs with picomolar and low-nanomolar
activities against wild-type HIV-1 and key variants that also show much improved
solubility and lower cytotoxicity than recently approved drugs in the class.
PMID- 27485605
TI - Improving drug safety: From adverse drug reaction knowledge discovery to clinical
implementation.
AB - Adverse drug reactions (ADRs) are a major public health concern, causing over
100,000 fatalities in the United States every year with an annual cost of $136
billion. Early detection and accurate prediction of ADRs is thus vital for drug
development and patient safety. Multiple scientific disciplines, namely
pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing
the ADR problem from different perspectives. With the same goal of improving drug
safety, this article summarizes and links the research efforts in the multiple
disciplines into a single framework from comprehensive understanding of the
interactions between drugs and biological system and the identification of
genetic and phenotypic predispositions of patients susceptible to higher ADR
risks and finally to the current state of implementation of medication-related
decision support systems. We start by describing available computational
resources for building drug-target interaction networks with biological
annotations, which provides a fundamental knowledge for ADR prediction. Databases
are classified by functions to help users in selection. Post-marketing
surveillance is then introduced where data-driven approach can not only enhance
the prediction accuracy of ADRs but also enables the discovery of genetic and
phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR
requires well organized patient genetics information and analysis by
pharmacogenomic approaches. Finally, current state of clinical decision support
systems is presented and described how clinicians can be assisted with the
integrated knowledgebase to minimize the risk of ADR. This review ends with a
discussion of existing challenges in each of disciplines with potential solutions
and future directions.
PMID- 27485606
TI - Exploring the threshold premium for viable community based health insurance
schemes in Nigeria.
AB - BACKGROUND: The national health insurance scheme of Nigeria recently proposed a
national premium for community based insurance scheme. This study determined the
capacity of households in the rural and urban areas in Nigeria to pay for the
premium and different hypothetical health insurance schemes namely national
health insurance scheme, national urban health insurance scheme, national rural
health insurance scheme and regional health insurance schemes. It determined the
likely impact of different premiums on membership across socio-economic status
quintiles, and then determined the threshold premium affordable to rural and
urban households. RESULTS: The results show that the mean capacity to pay for the
households in different regions ranged from US$194 +/- 100 to US$986 +/- 907. The
threshold premiums of the national health insurance scheme, urban national health
insurance and rural health insurance schemes were US$66, US$154 and US$53
respectively. CONCLUSIONS: Overall, the threshold premium for rural national
health insurance scheme and national health insurance schemes were affordable to
the lowest socio economic group. Hence, it is recommended that threshold premium
for rural national health insurance scheme be adopted as the maximum premium not
to be exceeded in the proposed national health insurance scheme.
PMID- 27485607
TI - Associations between physical activity patterns and dietary patterns in a
representative sample of Polish girls aged 13-21 years: a cross-sectional study
(GEBaHealth Project).
AB - BACKGROUND: Similar to other countries, trends of decreasing levels of physical
activity (PA) and an increasing prevalence of unhealthy dietary patterns are
observed among girls in Poland. Better understanding of potentially inter-related
behaviours within this population can help to design tailored interventions. The
purpose of this study was to determine associations between PA patterns and
dietary patterns in a representative sample of Polish girls. METHODS: Girls aged
13-21 years (n = 1107) were randomly selected for the study. PA was assessed
using International Physical Activity Questionnaire - Long (IPAQ-L). Dietary data
were collected with food frequency questionnaires. PA patterns and dietary
patterns were drawn separately by Principal Component Analysis (PCA). Logistic
regression was used to find the associations between PA patterns and dietary
patterns. RESULTS: Four major PA patterns ('School/work activity', 'Active
recreation', 'Yard activity' and 'Walking and domestic activity') and four
dietary patterns ('Traditional Polish', 'Fruit & vegetables', 'Fast food &
sweets' and 'Dairy & fats') were identified. Level of PA was the highest in the
upper tertile of 'School/work activity' pattern (mean 1372.2 MET-minutes/week, 95
% Confidence Intervals [CI]: 1285.9-1458.5). Girls in upper tertiles of 'Yard
activity', 'Active recreation' and 'School/work activity' patterns had
significantly higher chances of being in the upper tertile of the 'Fruit and
vegetables' dietary pattern (odds ratio [OR] 2.17, 95 % CI: 1.50-3.14, p <
0.0001; OR 2.02, 95 % CI: 1.41-2.91; p < 0.001 and OR 1.76, 95 % CI: 1.24-2.51, p
< 0.01 respectively; all adjusted for confounders) in comparison to bottom
tertiles. Weak, but significant inverse associations were found between upper
tertiles of 'Active recreation' and 'Yard activity' patterns and unhealthy
dietary patterns. CONCLUSIONS: We found associations between PA patterns and
dietary patterns in the population of Polish girls. Girls with the highest
adherence to the 'School/work activity' pattern had the highest levels of PA and
presented pro-healthy dietary behaviours. School should be recognised as
potentially efficient and important setting to maximise girls' PA potential. The
after-school time is the area that should also be targeted to increase daily PA
or to at least sustain the level of PA after completing education.
PMID- 27485608
TI - Genome-wide characterization of non-reference transposons in crops suggests non
random insertion.
AB - BACKGROUND: Transposons (transposable elements or TEs) are DNA sequences that can
change their position within the genome. A large number of TEs have been
identified in reference genome of each crop(named accumulated TEs), which are the
important part of genome. However, whether there existed TEs with different
insert positions in resequenced crop accession genomes from those of reference
genome (named non-reference transposable elements, non-ref TEs), and what the
characteristics (such as the number, type and distribution) are. To identify and
characterize crop non-ref TEs, we analyzed non-ref TEs in more than 125
accessions from rice (Oryza sativa), maize (Zea mays) and sorghum (Sorghum
bicolor) using resequenced data with paired-end mapping methods. RESULTS: We
identified 13,066, 23,866 and 35,679 non-ref TEs in rice, maize and sorghum,
respectively. Genome-wide characterization analysis shows that most of non-ref
TEs were unique and non-ref TE classes shows different among rice, maize and
sorghum. We found that non-ref TEs have a strong positive correlation with gene
number and have a bias toward insertion near genes, but with a preference for
avoiding coding regions in maize and sorghum. The genes affected by non-ref TE
insertion were functionally enriched for stress response mechanisms in all three
crops. CONCLUSIONS: These observations suggest that transposon insertion is not a
random event and it makes genomic diversity, which may affect the intraspecific
adaption and evolution of crops.
PMID- 27485609
TI - Providing mental health first aid in the workplace: a Delphi consensus study.
AB - BACKGROUND: Mental health problems are common in the workplace, but workers
affected by such problems are not always well supported by managers and co
workers. Guidelines exist for the public on how to provide mental health first
aid, but not specifically on how to tailor one's approach if the person of
concern is a co-worker or employee. A Delphi consensus study was carried out to
develop guidelines on additional considerations required when offering mental
health first aid in a workplace context. METHODS: A systematic search of
websites, books and journal articles was conducted to develop a questionnaire
with 246 items containing actions that someone may use to offer mental health
first aid to a co-worker or employee. Three panels of experts from English
speaking countries were recruited (23 consumers, 26 managers and 38 workplace
mental health professionals), who independently rated the items over three rounds
for inclusion in the guidelines. RESULTS: The retention rate of the expert
panellists across the three rounds was 61.7 %. Of the 246 items, 201 items were
agreed to be important or very important by at least 80 % of panellists. These
201 endorsed items included actions on how to approach and offer support to a co
worker, and additional considerations where the person assisting is a supervisor
or manager, or is assisting in crisis situations such as acute distress.
CONCLUSIONS: The guidelines outline strategies for a worker to use when they are
concerned about the mental health of a co-worker or employee. They will be used
to inform future tailoring of Mental Health First Aid training when it is
delivered in workplace settings and could influence organisational policies and
procedures.
PMID- 27485610
TI - "Talk with me": perspectives on services for men with problem gambling and
housing instability.
AB - BACKGROUND: Problem gambling and homelessness are recognized as important public
health concerns that significantly impact individuals, their friends and
families, communities and broader society. We aimed to explore the experiences
with health and social services of men who had histories of problem gambling and
housing instability in Toronto, Ontario. METHODS: We used a community-based
participatory approach with a multi-service agency serving low-income
individuals. We conducted qualitative interviews with men (n = 30) who had
experienced problem gambling and housing instability. Our interviews employed
open-ended questions to elicit men's perceptions of services related to housing
instability, problem gambling and other comorbid conditions (e.g., mental
illness, substance use). We reviewed relevant themes related to experiences with
services (e.g., Use of and feedback on: health and social services, housing
services, justice/legal aid services, substance use services, gambling services;
stigma; goals; triggers; physical health; coping strategies; finances;
relationships; barriers to services and recommendations for services). RESULTS:
The concept of person-centred engagement was identified as a main overarching
theme, and seemed to be lacking in most of the men's experiences of services.
Person-centred engagement for these men entailed empowerment and autonomy;
empathy, compassion and sincerity; respectful communication; and tailored and
holistic life plans. While there was a strong emphasis placed on independence,
the men identified the importance of positive therapeutic relationships as being
critical aspects of the recovery process. Based on our analyses, several
recommendations were identified: 1) Increasing general awareness of services for
problem gambling; 2) Delivering integrated services in a one-stop-shop; 3)
Addressing mental health with psychotherapy and pharmacotherapy; 4) Providing
timely access to prevention and recovery services; and 5) Enhancing life skills
with peer support. CONCLUSIONS: Our study highlighted that most of the men we
interviewed were not having their health and social needs met. Services need to
address the intersection of problem gambling, housing instability, and other
comorbidities. Ensuring services are grounded in person-centred engagement
appears to be critical for optimal service delivery.
PMID- 27485611
TI - Analysis of RTEL1 and PCDHGB6 promoter methylation in circulating-free DNA of
lung cancer patients using liquid biopsy: A pilot study.
AB - BACKGROUND: Analysis of epigenetic alterations such as methylation of circulating
free DNA (cf-DNA) expression significantly broadened perspectives of lung cancer
(LC) screening. Moreover, methylation of tumor suppressor genes may be analyzed
with non-invasive manner in patients' blood samples (liquid biopsy), what
underline necessity of detailed investigation of tumor cf-DNA. MATERIAL AND
METHODS: The purpose of current study was to assess methylation of RTEL1 and
PCDHGB6 promoter regions in cf-DNA of 70 LC patients and 80 healthy individuals
using qMSP-PCR technique. Methylation status of both genes has not been
investigated in cf-DNA of LC patients before. RESULTS: PCDHGB6 promoter
methylation was found in 41.4% of LC patients and in 1.3% of healthy individuals,
whereas promoter of RTEL1 was found methylated in 51.4% of LC patients and in
8.8% of healthy individuals. Combined analysis of two markers improved test
sensitivity up to 62.9% and specificity up to 90% with area under the curve (AUC)
in receiver operating curve (ROC) of 0.755. CONCLUSIONS: The evaluation of RTEL1
and PCDHGB6 promoter methylation may be an useful tool for non-invasive diagnosis
of LC in liquid biopsy.
PMID- 27485612
TI - Atomic resolution mechanistic studies of ribocil: A highly selective unnatural
ligand mimic of the E. coli FMN riboswitch.
AB - Bacterial riboswitches are non-coding RNA structural elements that direct gene
expression in numerous metabolic pathways. The key regulatory roles of
riboswitches, and the urgent need for new classes of antibiotics to treat multi
drug resistant bacteria, has led to efforts to develop small-molecules that mimic
natural riboswitch ligands to inhibit metabolic pathways and bacterial growth.
Recently, we reported the results of a phenotypic screen targeting the riboflavin
biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to
the identification of ribocil, a small molecule inhibitor of the flavin
mononucleotide (FMN) riboswitch controlling expression of this biosynthetic
pathway. Although ribocil is structurally distinct from FMN, ribocil functions as
a potent and highly selective synthetic mimic of the natural ligand to repress
riboswitch-mediated ribB gene expression and inhibit bacterial growth both in
vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of
binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and
structure-activity relationship guided efforts to generate more potent analogs.
PMID- 27485613
TI - Setting up computed tomography automatic tube current modulation systems.
AB - Automatic tube current modulation (ATCM) on CT scanners can yield significant
reductions in patient doses. Modulation is based on x-ray beam attenuation in
body tissues obtained from scan projection radiographs (SPRs) and aims to
maintain the same level of image quality throughout a scan. Noise level is
important in judging image quality, but tissues in larger patients exhibit higher
contrast resulting from the presence of fat. CT scanner manufacturers use
different metrics to assess image quality. Some employ a simple measure of image
noise, while others adopt a measure related to a reference image that accepts
higher noise levels in more attenuating parts with higher contrast. At the
present time there is no standard method for testing ATCM. This paper reviews the
operation of different ATCM systems, considers options for testing, and sets out
a framework that could be used for optimizing clinical protocols. If dose and
image quality can be established for a reference phantom, the modulation
performed by ATCM systems can be characterised using anatomical phantoms or
geometrical elliptical phantoms which may be conical or include sections of
varying dimension. For scanners using a reference image or mAs, selection of the
image quality reference determines other factors. However, for scanners using a
noise reference, a higher noise level should be selected for larger patients to
avoid high doses, and the operator should ensure that appropriate limits are set
for mA modulation. Other factors that need to be considered include the SPRs used
to plan the ATCM and image thickness. Users should be aware of the mode of
operation of the ATCM system on their CT scanner, and be familiar with the
effects of changing different protocol parameters. The behaviour of ATCM systems
should be established through testing of each CT scanner with suitable phantoms
during commissioning.
PMID- 27485614
TI - Indicative role of urban tree vegetation in the assessment of natural and man
made complex in Akhtubinsk and its local areas.
AB - The study was conducted as a part of the selection of the objects of
phytomonitoring for the environmental assessment on the value of fluctuating
asymmetry of bilateral morphological parameters. The territorial structure of
flora of tree layer in Akhtubinsk and its local areas was determined as of 2013.
The living conditions and species and quantitative composition of the tree layer
of urban landscape were examined. The vital status of trees was assessed on a ten
point scale of the categories: good condition; satisfactory; weakened plants
(Bukharina and Dvoeglazova 2010). The quantitative assessment of biodiversity of
tree layer was made on the basis of conventional indices of individual dominance
and dominating structures, as well as the method of multivariate statistical
analysis. This is an objective method that has been used by other authors in a
variety of the environmental studies for a long time, but it has not been
actively used in the studies of the Astrakhan area vegetation yet. The results of
the study make it possible to believe that the most appropriate indicator of tree
vegetation for biomonitoring of intact floodplain, residential and recreational
areas in the urban territory in the arid climate of the Volga-Akhtuba floodplain
is the Chinese elm (Ulmus parvifolia Jacq.),as the most widespread, numerous and
sensitive. It is noted that the tree vegetation cannot be a universal
bioindicator of the urban environment in Akhtubinsk and its local areas by
fluctuating asymmetry of bilateral morphological parameters.
PMID- 27485615
TI - Impact assessment of PM10 cement plants emissions on urban air quality using the
SCIPUFF dispersion model.
AB - The Second-order Closure Integrated Puff (SCIPUFF) model was used to study the
impact on urban air quality caused by two cement plants emissions located near
the city of Caserta, Italy, during the entire year of 2015. The simulated and
observed PM10 concentrations were compared using three monitoring stations
located in urban and sub-urban area of Caserta city. Both simulated and observed
concentrations are shown to be highest in winter, lower in autumn and spring and
lowest in summer. Model results generally follow the pattern of the observed
concentrations but have a systematic under-prediction of the concentration
values. Measures of the bias, NMSE and RMSE indicate a good correlation between
observed and estimated values. The SCIPUFF model data analysis suggest that the
cement plants are major sources for the measured PM10 values and are responsible
for the deterioration of the urban air quality in the city of Caserta.
PMID- 27485616
TI - Bioaccumulation of heavy metals in crop plants grown near Almeda Textile Factory,
Adwa, Ethiopia.
AB - The contents of heavy metals cadmium (Cd), cobalt (Co), chromium (Cr), copper
(Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) present in water
(wastewater and wetland), soils, and food crops collected from the vicinity of
Almeda Textile Factory were quantified using Flame Atomic Absorption Spectrometer
(FAAS) in order to assess the environmental impact of the textile factory. The
contents of heavy metals determined in the wastewater were found below the
recommended limit set by WHO and United States Environmental Protection Agency
(US EPA) except for Cr, which was found slightly higher than WHO permissible
limit. Besides, the contents of the heavy metals determined in soils were below
the permissible level of FAO/WHO and Canada maximum allowable limits. Moreover,
only the concentrations of Cd and Pb were found above the permissible level set
by FAO/WHO in the crop plants studied. Generally, the mean concentrations of
heavy metals in the plants were in the decreasing order of: Mn > Zn > Cu > Pb >
Ni > Co > Cr > Cd. Nevertheless, higher bioconcentration factor (BCF) was found
for Cd (0.108-1.156) followed by Zn (0.081-0.499). In conclusion, comparison of
heavy metal concentrations with the permissible limits in all collected sample
types i.e. water, soil, and crop plants did not show significant pollution from
the factory.
PMID- 27485617
TI - In vitro characterization of an osteoinductive biphasic calcium phosphate in
combination with recombinant BMP2.
AB - BACKGROUND: The repair of alveolar bone defects with growth factors and bone
grafting materials has played a pivotal role in modern dentistry. Recombinant
human bone morphogenetic protein-2 (rhBMP2), an osteoinductive growth factor
capable of cell recruitment and differentiation towards the osteoblast lineage,
has been utilized in combination with various biomaterials to further enhance new
bone formation. Recently, a group of novel biphasic calcium phosphate (BCP) bone
grafting materials have been demonstrated to possess osteoinductive properties by
demonstrating signs of ectopic bone formation. The aim of the present study was
to study the effects of rhBMP2 in combination with osteoinductive BCP bone grafts
on osteoblast cell behaviour. METHODS: MC3T3-E1 pre-osteoblasts were seeded on 1)
control tissue culture plastic, 2) 10 mg of BCP alone, 3) 100 ng rhBMP2, and 4)
100 ng rhBMP2+ 10 mg of BCP and analyzed for cell recruitment via a Transwell
chamber, proliferation via an MTS assay and differentiation as assessed by
alkaline phosphatase (ALP) activity, alizarin red staining and real-time PCR for
osteoblast differentiation markers including Runx2, collagen1, ALP, and
osteocalcin (OCN). RESULTS: rhBMP2 was able to significantly upregulate cell
recruitment whereas the addition of BCP as well as BCP alone had no additional
ability to improve osteoblast recruitment. Both BCP and rhBMP2 were able to
significantly increase cell proliferation at 3 and 5 days post seeding and cell
number was further enhanced when rhBMP2 was combined with BCP. In addition, the
combination of rhBMP2 with BCP significantly improved ALP activity at 7 and 14
days post seeding, alizarin red staining at 14 days, and mRNA levels of Runx2,
ALP and osteocalcin when compared to cells seeded with rhBMP2 alone or BCP alone.
CONCLUSIONS: The results from the present study demonstrate that 1) the
osteoinductive potential of BCP bone particles is equally as osteopromotive as
rhBMP2 on in vitro osteoblast differentiation and 2) BCP particles in combination
with rhBMP2 is able to further increase the osteopromotive differentiation of
osteoblasts in vitro when compared to either rhBMP2 alone or BCP alone. Future
animal testing is further required to investigate this combination approach on
new bone formation.
PMID- 27485619
TI - What socioeconomic factors are associated with different levels of antenatal care
visits in Bangladesh? A behavioral model.
AB - We identify the socioeconomic determinants of three levels of antenatal care
(ANC) visits (no, intermediate [1-3], and recommended [>=4]) in Bangladesh using
a behavior model framework for health care utilization. Using multinomial
logistic regression, we found that different levels of visits had different
determinants; for example, media exposure increased the likelihood of
intermediate compared with no visits while desire for pregnancy increased the
likelihood of recommended compared with intermediate visits. We therefore
highlight that ANC policies or interventions should be target-group specific
because determinants differ depending on level of ANC visits.
PMID- 27485618
TI - Health services research of integrative oncology in palliative care of patients
with advanced pancreatic cancer.
AB - BACKGROUND: Pancreatic cancer has a dire prognosis and is associated with a high
mortality. Palliative patients have special needs and often seek help in
integrative oncological concepts (IO) that combine conventional and complementary
therapies. Nevertheless there are few recommendations regarding IO in current
cancer guidelines. The aims of this study were to report on implementation of IO
in everyday palliative care and to analyze patient survival in advanced
pancreatic cancer. METHODS: This multicenter observational study investigates the
implementation of IO and length of survival of patients suffering from advanced
pancreatic cancer (stage IV). We analyzed patient's survival by employing
multivariable proportional hazard models using different parametric distribution
functions and compared patients receiving chemotherapy only, a combination of
chemotherapy and Viscum album (VA) treatment, and VA treatment only. RESULTS:
Records of 240 patients were analyzed. Complementary therapy showed high
acceptance (93 %). Most frequent therapy was VA treatment (74 %) that was often
administered concomitantly to chemotherapy (64 %). Both therapies had positive
effects on patient survival as they had significant negative effects on the
hazard in our log-normal model. A second analysis showed that patients with
combined chemotherapy and VA therapy performed significantly better than patients
receiving only chemotherapy (12.1 to 7.3 month). Patients receiving only VA
therapy showed longer survival than those receiving neither chemotherapy nor VA
therapy (5.4 to 2.5 months). Our data demonstrates that IO can be implemented in
the everyday care of patients without disregarding conventional treatment.
Patients combining VA with chemotherapy showed longest survival. CONCLUSIONS: Our
data demonstrate the importance and potential of health services research showing
that IO treatment can be successfully implemented in the every-day care of
patients suffering from advanced pancreatic cancer. Patients combining VA with
chemotherapy showed longest survival. To address patients' needs adequately,
future cancer guidelines might increasingly include comments on complementary
treatment options in addition to conventional therapies. Further studies should
investigate the effect of complementary treatments on survival and quality of
life in more detail.
PMID- 27485620
TI - Interactive effects of phosphorus and Pseudomonas putida on chickpea (Cicer
arietinum L.) growth, nutrient uptake, antioxidant enzymes and organic acids
exudation.
AB - Phosphorus (P) availability in alkaline soils of arid and semi-arid regions is a
major constraint for decreased crop productivity. Use of plant growth promoting
rhizobacteria (PGPR) may enhance plant growth through the increased plant
antioxidation activity. Additionally, PGPR may increase nutrient uptake by plants
as a result of induced root exudation and rhizosphere acidification. The current
study was aimed to investigate combined effects of P and Pesudomonas putida
(PGPR) on chickpea growth with reference to antioxidative enzymatic activity and
root exudation mediated plant nutrient uptake, particularly P. Half of the seeds
were soaked in PGPR solution, whereas others in sterile water and latter sown in
soils. Plants were harvested 8 weeks after onset of experiment and analyzed for
leaf nutrient contents, antioxidant enzymes activities and organic acids
concentrations. Without PGPR, P application (+P) increased various plant growth
attributes, plant uptake of P and Ca, soil pH, citric acid and oxalic acid
concentrations, whereas decreased the leaf POD enzymatic activity as compared to
the P-deficiency. PGPR supply both under -P and +P improved the plant growth,
plant uptake of N, P, and K, antioxidative activity of SOD and POD enzymes and
concentrations of organic acids, whereas reduced the rhizosphere soil pH. Growth
enhancement by PGPR supply was related to higher plant antioxidation activity as
well as nutrient uptake of chickpea including P as a result of root exudation
mediated rhizosphere acidification.
PMID- 27485621
TI - Sleep problems and temperament in young children with Down syndrome and typically
developing controls.
AB - BACKGROUND: Although group differences have been found between children with Down
syndrome (DS) and typically developing (TD) children when considering sleep
problems and temperament independently, none of the research conducted to date
has examined sleep-temperament associations in children with DS. The present
research was conducted to determine (1) whether the sleep problems experienced by
children with DS are associated with temperament or (2) if the demonstrated
relations between sleep and temperament differ from those that are observed in TD
children. METHOD: The present study included examination of relations between
parent-reported sleep problems and temperament in 19 children with DS and 20 TD
controls matched on developmental age. RESULTS: The results revealed group
differences in temperament and sleep problems. Mediation models indicated that
temperament (effortful control and inhibitory control) mediated the association
between group and sleep problems; sleep problems also mediated the association
between group and temperament (effortful and inhibitory control). CONCLUSION:
Findings indicated that sleep problems may serve as both cause and consequence of
variability in effortful and inhibitory control and provide insight as to future
experimental studies that should be conducted to better elucidate these
relations.
PMID- 27485622
TI - Dual-immuno-MS technique for improved differentiation power in heterodimeric
protein biomarker analysis: determination and differentiation of human chorionic
gonadotropin variants in serum.
AB - If the biomarker potential of intact heteromers and their free subunits is
different, differentiation between these forms may reveal important clinical
information. Such differentiation may however be analytically challenging. One
possible way of circumventing this challenge is by performing a dual-immuno-MS
approach. In the present paper, a two-step immunoaffinity sample preparation step
is succeeded by digestion and subsequent LC-MS analysis to provide high
sensitivity quantification and differentiation between the heterodimer human
chorionic gonadotropin (hCG) and its free beta-subunit in serum. Intact and free
variants are captured in two separate immunoextraction steps in order to increase
the differentiation power of the method. Intact heterodimer variants were
depleted prior to free subunit variants in order to incorporate a method quality
control. The method was optimized for serum samples. A fully validated immuno-MS
method was used as foundation, and partial validation according to the European
Medicines Agency's (EMA) guidelines on validation of bioanalytical methods was
performed for the dual approach. An accelerated digestion step was incorporated
making batch processing of samples within 1 day possible (approx. 3.5 h of sample
preparation including digestion). Acceptable linearity (R (2) >= 0.990 for four
variants and R (2) of 0.920 and 0.966 for the remaining two) and specificity were
demonstrated, and the method was robust toward varying levels of intact
heterodimer versus free subunit. The method was also successfully tested on
realistic samples, demonstrating both the differences in total hCG and the
distribution between intact hCG and its free beta-subunit in real samples.
Graphical abstract Schematic overview of the dual immuno-MS process.
PMID- 27485623
TI - An approach to optimize sample preparation for MALDI imaging MS of FFPE sections
using fractional factorial design of experiments.
AB - A standardized workflow for matrix-assisted laser desorption/ionization imaging
mass spectrometry (MALDI imaging MS) is a prerequisite for the routine use of
this promising technology in clinical applications. We present an approach to
develop standard operating procedures for MALDI imaging MS sample preparation of
formalin-fixed and paraffin-embedded (FFPE) tissue sections based on a novel
quantitative measure of dataset quality. To cover many parts of the complex
workflow and simultaneously test several parameters, experiments were planned
according to a fractional factorial design of experiments (DoE). The effect of
ten different experiment parameters was investigated in two distinct DoE sets,
each consisting of eight experiments. FFPE rat brain sections were used as
standard material because of low biological variance. The mean peak intensity and
a recently proposed spatial complexity measure were calculated for a list of 26
predefined peptides obtained by in silico digestion of five different proteins
and served as quality criteria. A five-way analysis of variance (ANOVA) was
applied on the final scores to retrieve a ranking of experiment parameters with
increasing impact on data variance. Graphical abstract MALDI imaging experiments
were planned according to fractional factorial design of experiments for the
parameters under study. Selected peptide images were evaluated by the chosen
quality metric (structure and intensity for a given peak list), and the
calculated values were used as an input for the ANOVA. The parameters with the
highest impact on the quality were deduced and SOPs recommended.
PMID- 27485624
TI - Sensitive and specific detection of miRNA using an isothermal exponential
amplification method using fluorescence-labeled LNA/DNA chimera primers.
AB - MicroRNAs (miRNAs) are currently considered as potential biomarkers for various
human diseases. In the present study, miRNA-triggered real-time fluorescent
isothermal reaction with exponential amplification (ReFIRE) with or without
Thermus aquaticus MutS (Taq MutS) was developed to analyze miRNAs using DNA
polymerase, a nicking endonuclease, and fluorescently labeled primers. In the
absence of Taq MutS, the ReFIRE system permitted the detection of 100 ymol of
targeted miRNA in 80 min. However, this system enabled limited differentiation
between homologous miRNA family members. Upon addition of Taq MutS to the ReFIRE
system, non-specific amplification generated from the mishybridization between
primers and primer dimers or primers and the template duplex was eliminated. The
addition of Taq MutS enabled the ultrasensitive detection of as little as 10 ymol
of targeted miRNAs in 50 min, which corresponds to less than 10 copies of miRNAs
in a total volume of 20 MUl. Additionally, the assay exhibited a dynamic range of
up to 12 orders of magnitude. The ReFIRE system also showed high specificity,
enabling differentiation between homologous miRNA family members exhibiting only
single-base differences. The sensitivity, specificity, and dynamic range
associated with this system were greater than most currently available miRNA
isothermal amplification assays. Moreover, when target-specific primers were
labeled with different fluorescent reporters, multiplex analysis was easily
performed in a single tube, permitting accurate normalization of miRNA
expression. This simple, fast, ultrasensitive, highly specific, and easy-to
multiplex method could significantly contribute to research investigations
pertaining to the biological roles of miRNA, as well as clinical diagnosis of
various diseases that involve miRNA disruptions. Graphical Abstract The principle
of ReFIRE system.
PMID- 27485625
TI - A novel carbon material with nanopores prepared using a metal-organic framework
as precursor for highly selective enrichment of N-linked glycans.
AB - Protein glycosylation plays a key role in many biological processes. In this
study, a novel carbon material with nanopores was prepared by carbonization of
metal-organic framework (MOF) Mil-101(Cr). The parent MOF assembled from metal
ions with bridging organic linkers had many fascinating properties, such as
ultrahigh surface area, suitable nanopore structure, and especially a large
amount of carbon after being calcined. Due to the strong interactions between
carbon and glycans as well as the size-exclusion effect of pore against protein,
the N-linked glycans from standard glycoprotein or complex human serum proteins
could be identified with high efficiency. The simple synthesis method as well as
good enrichment efficiency made this novel carbon material a promising tool for
glycosylation research.
PMID- 27485626
TI - Recent advances and progress in the detection of bisphenol A.
AB - Bisphenol A (BPA) is an important industrial chemical used as a plasticizer in
polycarbonate and epoxy resins in the plastic and paper industries. Because of
its estrogenic properties, BPA has attracted increasing attention from many
researchers. This review focuses primarily on analytical methods for BPA
detection that have emerged in recent years. We present and discuss the
advantages and disadvantages of sample preparation techniques (e.g., solvent
extraction, solid-phase extraction, molecularly imprinted polymer solid-phase
extraction, and micro-extraction techniques) and analytical methods (e.g., liquid
chromatography, liquid chromatography-mass spectrometry, gas chromatography-mass
spectrometry, capillary electrophoresis, immunoassay, and several novel sensors).
We also discuss expected future developments for the detection of BPA. Graphical
Abstract This review focuses primarily on the recent development in the detection
of bisphenol A including sample pre-treatment and analytical methods.
PMID- 27485627
TI - Exploring the flexible chemistry of 4-fluoro-3-nitrophenyl azide for biomolecule
immobilization and bioconjugation.
AB - Bioconjugation and functionalization of polymer surfaces are two major tasks in
materials chemistry which are accomplished using a variety of coupling agents.
Immobilization of biomolecules onto polymer surfaces and the construction of
bioconjugates are essential requirements of many biochemical assays and chemical
syntheses. Different linkers with a variety of functional groups are used for
these purposes. Among them, the benzophenones, aryldiazirines, and arylazides
represent the most commonly used photolinker to produce the desired chemical
linkage upon their photo-irradiation. In this review, we describe the versatile
applications of 4-fluoro-3-nitrophenyl azide, one of the oldest photolinkers used
for photoaffinity labeling in the late 1960s. Surprisingly, this photolinker,
historically known as 1-fluoro-2-nitro-4-azidobenzene (FNAB), has remained
unexplored for a long time because of apprehension that FNAB forms ring-expanded
dehydroazepine as a major product and hence cannot activate an inert polymer. The
first evidence of photochemical activation of an inert surface by FNAB through
nitrene insertion reaction was reported in 2001, and the FNAB-activated surface
was found to conjugate a biomolecule without any catalyst, reagent, or
modification. FNAB has distinct advantages over perfluorophenyl azide
derivatives, which are contemporary nitrene-generating photolinkers, because of
its simple, single-step preparation and ease of thermochemical and photochemical
reactions with versatile polymers and biomolecules. Covering these aspects, the
present review highlights the flexible chemistry of FNAB and its applications in
the field of surface engineering, immobilization of biomolecules such as
antibodies, enzymes, cells, carbohydrates, oligonucleotides, and DNA aptamers,
and rapid diagnostics. Graphical Abstract An overview of the FNAB-engineered
activated polymer surfaces for covalent ligation of versatile biomolecules.
PMID- 27485628
TI - Some ruminations on graduate students.
PMID- 27485629
TI - Investigation of Growth Phase-Dependent Acid Tolerance in Bifidobacteria longum
BBMN68.
AB - The underlying mechanisms imparting the growth phase-dependent acid tolerance
have not been extensively investigated. In this study, we compared the acid
resistance of the Bifidobacterium longum strain BBMN68 from different growth
phases at lethal pH values (pH 2.5, 3.0, and 3.5), and analyzed the activity of
H(+)-ATPase, the composition of fatty acids, and the mRNA abundance of ffh, uvrA,
recA, lexA, groES, and dnaK in cells from different growth phases. The results
indicated that the survival rates of cells from early stationary (ES) and late
stationary (LS) growth phases at lethal pH values were significantly higher than
those of exponential growth phase cells. Our findings indicated that by inducing
a continuously auto-acidizing environment during cell growth, the acid resistance
of ES and LS cells was strengthened. The higher activity of H(+)-ATPase, the
decrease in unsaturated fatty acids, and the increased expression of genes
involved in DNA repair and protein protection in the cells in stationary growth
phase were all implicated in the significantly increased acid resistance of ES
and LS cells compared with exponential growth phase cells of the B. longum strain
BBMN68.
PMID- 27485630
TI - Is Stem Cell Transplantation Ready for Prime Time in Diabetic Polyneuropathy?
AB - Diabetic polyneuropathy (DPN) is the most common complication that emerges early
in patients who have diabetes. Curative treatment for overt or symptomatic DPN
has not been established, requiring much effort to explore new modalities. Thus,
the use of various kinds of stem cells as a potential therapeutic option for DPN
is of particular interest. The beneficial effects were proposed to be attributed
to either cytokine released from transplanted stem cells or the differentiation
of stem cells to substitute the damaged peripheral nerve. Furthermore, based on
the concept that humoral factors secreted from stem cells play a pivotal role in
tissue regeneration, the utilization of conditioned medium derived from the stem
cell culture serves as a novel tool for regenerative therapy. However, many
questions have not been yet answered to determine whether stem cell therapy is
essential in clinical application of DPN. In this report, we review the current
status of preclinical studies on stem cell therapy for DPN and discuss future
prospects.
PMID- 27485631
TI - Aggregatibacter aphrophilus chronic lacrimal canaliculitis: a case report.
AB - BACKGROUND: Chronic canaliculitis is often misdiagnosed as conjunctivitis,
delaying proper documentation and management. Aggregatibacter aphrophillus has
not been implicated in chronic canaliculitis. CASE PRESENTATION: We report a case
of unilateral chronic epiphora associated with chronic lacrimal canaliculitis
resistant to prolonged topical antibiotic treatment in a 65-year-old woman
without notable medical history. Canaculotomy, curettage with removal of
concretions and tubing with silicone stent for six weeks resolved this chronic
infection. Culturing lacrimal secretions and concretions yielded Aggregatibacter
aphrophilus in pure culture. Histological analyses showed elongated seed clusters
surrounded by neutrophils. Fluorescence in Situ Hybridization confirmed the
presence of bacteria in two distinctive concretions. CONCLUSION: This first
documented case of A. aphrophilus chronic lacrimal canaliculitis illustrates that
optimal surgical management of chronic lacrimal canaliculitis allows for both
accurate microbiological diagnosis and treatment.
PMID- 27485632
TI - Dual pharmacological inhibition of glutathione and thioredoxin systems synergizes
to kill colorectal carcinoma stem cells.
AB - NRF2 stabilizes redox potential through genes for glutathione and thioredoxin
antioxidant systems. Whether blockade of glutathione and thioredoxin is useful in
eliminating cancer stem cells remain unknown. We used xenografts derived from
colorectal carcinoma patients to investigate the pharmacological inhibition of
glutathione and thioredoxin systems. Higher expression of five glutathione S
transferase isoforms (GSTA1, A2, M4, O2, and P1) was observed in xenograft
derived spheroids than in fibroblasts. Piperlongumine (2.5-10 MUmol/L) and
auranofin (0.25-4 MUmol/L) were used to inhibit glutathione S-transferase pi and
thioredoxin reductase, respectively. Piperlongumine or auranofin alone up
regulated the expression of NRF2 target genes, but not TP53 targets. While
piperlongumine showed modest cancer-specific cell killing (IC50 difference
between cancer spheroids and fibroblasts: P = 0.052), auranofin appeared more
toxic to fibroblasts (IC50 difference between cancer spheroids and fibroblasts: P
= 0.002). The synergism of dual inhibition was evaluated by determining the
Combination Index, based on the number of surviving cells with combination
treatments. Molar ratios indicated synergism in cancer spheroids, but not in
fibroblasts: (auranofin:piperlongumine) = 2:5, 1:5, 1:10, and 1:20. Cancer
specific cell killing was achieved at the following drug concentrations
(auranofin:piperlongumine): 0.25:2.5 MUmol/L, 0.5:2.5 MUmol/L, or 0.25:5 MUmol/L.
The dual inhibition successfully decreased CD44v9 surface presentation and
delayed tumor emergence in nude mouse. However, a small subpopulation
persistently survived and accumulated phosphorylated histone H2A. Such
"persisters" still retained lesser but significant tumorigenicity. Thus, dual
inhibition of glutathione S-transferase pi and thioredoxin reductase could be a
feasible option for decreasing the tumor mass and CD44v9-positive fraction by
disrupting redox regulation.
PMID- 27485633
TI - Access to health for refugees in Greece: lessons in inequalities.
AB - Eastern Greek islands have been direct passageways of (mainly Syrian) refugees to
the European continent over the past year. However, basic medical care has been
insufficient. Despite calls for reform, the Greek healthcare system has for many
years been costly and dysfunctional, lacking universal equity of access. Thus,
mainly volunteers look after the refugee camps in the Greek islands under adverse
conditions. Communicable diseases, trauma related injuries and mental health
problems are the most common issues facing the refugees. The rapid changes in the
epidemiology of multiple conditions that are seen in countries with high
immigration rates, like Greece, demand pragmatic solutions. Best available
knowledge should be used in delivering health interventions. So far, Greece is
failed by international aid, and cross-border policies have not effectively
tackled underlying reasons for ill-health in this context, like poverty, conflict
and equity of access.
PMID- 27485635
TI - Sex allocation conflict between queens and workers in Formica pratensis wood ants
predicts seasonal sex ratio variation.
AB - Sex allocation theory predicts parents should adjust their investment in male and
female offspring in a way that increases parental fitness. This has been shown in
several species and selective contexts. Yet, seasonal sex ratio variation within
species and its underlying causes are poorly understood. Here, we study sex
allocation variation in the wood ant Formica pratensis. This species displays
conflict over colony sex ratio as workers and queens prefer different investment
in male and female offspring, owing to haplodiploidy and relatedness asymmetries.
It is unique among Formica ants because it produces two separate sexual offspring
cohorts per season. We predict sex ratios to be closer to queen optimum in the
early cohort but more female-biased and closer to worker optimum in the later
one. This is because the power of workers to manipulate colony sex ratio varies
seasonally with the availability of diploid eggs. Consistently, more female
biased sex ratios in the later offspring cohort over a three-year sampling period
from 93 colonies clearly support our prediction. The resulting seasonal
alternation of sex ratios between queen and worker optima is a novel
demonstration how understanding constraints of sex ratio adjustment increases our
ability to predict sex ratio variation.
PMID- 27485634
TI - Mitofusin-2 is required for mouse oocyte meiotic maturation.
AB - Mitofusin-2 (Mfn2) is essential for embryonic development, anti-apoptotic events,
protection against free radical-induced lesions, and mitochondrial fusion in many
cells. However, little is known about its mechanism and function during oocyte
maturation. In this study, we found that Mfn2 was expressed in the cytoplasm
during different stages of mouse oocyte maturation. Mfn2 was mainly associated
with alpha-tubulin during oocyte maturation. Knockdown of Mfn2 by specific siRNA
injection into oocytes caused the mitochondrial morphology and quantity to
change, resulting in severely defective spindles and misaligned chromosomes. This
led to metaphase I arrest and the failure of first polar body extrusion.
Furthermore, Mfn2 depletion from GV stage oocytes caused the redistribution of
p38 MAPK in oocyte cytoplasm. These findings provide insights into potential
mechanisms of Mfn2-mediated cellular alterations, which may have significant
implications for oocyte maturation.
PMID- 27485636
TI - Bilberry extract, its major polyphenolic compounds, and the soy isoflavone
genistein antagonize the cytostatic drug erlotinib in human epithelial cells.
AB - Erlotinib (Tarceva(r)) is a chemotherapeutic drug approved for the treatment of
pancreatic cancer and non-small cell lung cancer. Its primary mode of action is
the inhibition of the epidermal growth factor receptor (EGFR), a receptor
tyrosine kinase (RTK). Recently, RTK-inhibiting polyphenols have been reported to
interact synergistically with erlotinib. Furthermore some anthocyanidins and
anthocyanin-rich berry extracts have been reported to inhibit tyrosine kinases,
including the EGFR, which raises the question of potential interactions with
erlotinib. Polyphenol-rich preparations such as berry- or soy-based products are
commercially available as food supplements. In the present study we tested a
bilberry extract, its major anthocyanin and potential intestinal degradation
products, as well as genistein, with respect to possible interactions with
erlotinib. Cell growth inhibition was assessed using the sulforhodamine B assay,
while interactions with EGFR phosphorylation were analyzed by SDS-PAGE/western
blotting with subsequent immunodetection. Genistein, bilberry extract,
delphinidin-3-O-glucoside and delphinidin were found to antagonize erlotinib
whereas phloroglucinol aldehyde was found to enhance cytostatic effects of the
drug on human epithelial A431 cells. Genistein also antagonized the EGFR
inhibitory effects of erlotinib, whereas bilberry anthocyanins showed no
significant interactions in this regard. Our data indicate that different
polyphenols are potentially able to impair the cytostatic effect of erlotinib in
vitro. Genistein interacts via the modulation of erlotinib-mediated EGFR
inhibition whereas bilberry anthocyanins modulated the growth-inhibitory effect
of erlotinib without affecting EGFR phosphorylation, thus indicating a different
mechanism of interference.
PMID- 27485637
TI - Dosimetric impact of different bladder and rectum filling during prostate cancer
radiotherapy.
AB - BACKGROUND: The aim of this study was to analyze the influence of volumetric
changes of bladder and rectum filling on the 3D dose distribution in prostate
cancer radiotherapy. METHODS: A total of 314 cone-beam CT (CBCT) image data sets
from 19 patients were enrolled in this study. For each CBCT, the bladder and
rectum were contoured and volume sizes were normalized to those on their original
CT. The daily delivered dose was recalculated on the CBCT images and the doses to
bladder and rectum were investigated. Linear regression analysis was performed to
identify the mean dose change of the volume change using SPSS 19. RESULTS: The
data show that the variances of the normalized volume of the bladder and the
rectum are 0.13-0.58 and 0.12-0.50 respectively. The variances of V70Gy, V60Gy,
V50Gy, V40Gy and V30Gy of bladder are bigger than those of rectum for 17
patients. The linear regression analysis indicates a 10 % increase in bladder
volume will cause a 5.6 % (+/-4.9 %) reduction in mean dose (p <0.05).
CONCLUSIONS: The bladder's volume change is more significant than that of the
rectum for the prostate cancer patient. The rectum volume variations are not
significant except for air bubbles, which change the shape and the position of
the rectum. The bladder volume variations may cause dose changes proportionately.
Monitoring the bladder's volume before fractional treatment delivery will be
crucial for accurate dose delivery.
PMID- 27485638
TI - Resistant mechanisms and molecular epidemiology of imipenem-resistant
Acinetobacter baumannii.
AB - The aim of the study was to investigate the resistant mechanisms and homology of
imipenem-resistant Acinetobacter baumannii (A. baumannii). A total of 46 non
duplicate imipenem-resistant A. baumannii clinical isolates were collected from
three tertiary hospitals between July, 2011 and June, 2012. The minimal
inhibitory concentrations (MICs) of antimicrobial agents were determined using
the agar dilution method. Phenylalanine-arginine beta-naphthylamide was used to
detect the presence of the efflux pump-mediated resistant mechanism. Polymerase
chain reaction was employed to amplify genes associated with drug resistance,
including beta-lactamase genes, efflux pump genes and outer membrane protein gene
CarO. A few amplicons were randomly selected and sequenced. Multilocus sequence
analysis (MLST) was employed in typing A. baumanni. A. baumannii was resistant to
imipenem, simultaneously showing resistance to several other antimicrobials. In
addtition, 13 A. baumannii were found to mediate drug resistance through
operation of the efflux pump. Of the various drug resistance genes tested, blaOXA
51 was present in 46 isolates, blaOXA-23 gene was present in 44 isolates and
blaNDM gene was found in only one strain. Other drug resistant-associated genes,
including blaKPC, blaIMP, blaOXA-24, blaOXA-58, blaSHV, blaGIM and blaVIM were
not detected. Mutation of adeS and outer membrane protein gene CarO were found in
a few of the imipenem-resistant isolates. The MLST analysis revealed that all 46
clinical isolates were clustered into 11 genotypes and the most frequent genotype
was ST208. In conclusion, beta-lactamase genes, genes involved in efflux pump and
mutation of outer membrane protein encoding gene may be important in mediating
imipenem resistance in A. baumannii. Of the 11 different genotypes, ST11 was
shared by the majority of A. baumannii, which may be due to horizontal transfer
of patients from hospitals.
PMID- 27485639
TI - Fungal biofilm composition and opportunities in drug discovery.
AB - Biofilm infections are exceptionally recalcitrant to antimicrobial treatment or
clearance by host immune responses. Within biofilms, microbes form adherent
multicellular communities that are embedded in an extracellular matrix. Many
prescribed antifungal drugs are not effective against biofilm infections owing to
several protective factors including poor diffusion of drugs through biofilms as
well as specific drug-matrix interactions. Despite the key roles that biofilms
play in infections, there is little quantitative information about their
composition and structural complexity because of the analytical challenge of
studying these dense networks using traditional techniques. Within this review,
recent work to elucidate fungal biofilm composition is discussed, with particular
attention given to the challenges of annotation and quantification of matrix
composition.
PMID- 27485640
TI - Vismodegib and risk of cholestatic injury: should we screen candidate patients?
PMID- 27485641
TI - LrABCF1, a GCN-type ATP-binding cassette transporter from Lilium regale, is
involved in defense responses against viral and fungal pathogens.
AB - MAIN CONCLUSION: The L. regale ATP-binding cassette transporter gene, LrABCF1
belonging to GCN subfamily, functions as a positive regulator of plant defense
against Cucumber mosaic virus, Tobacco rattle virus , and Botrytis cinerea in
petunia. ATP-binding cassette (ABC) transporters are essential for membrane
translocation in diverse biological processes, such as plant development and
defense response. Here, a general control non-derepressible (GCN)-type ABC
transporter gene, designated LrABCF1, was identified from Cucumber mosaic virus
(CMV)-induced cDNA library of L. regale. LrABCF1 was up-regulated upon
inoculation with CMV and Lily mottle virus (LMoV). Salicylic acid (SA) and
ethylene (ET) application and treatments with abiotic stresses such as cold, high
salinity, and wounding increased the transcript abundances of LrABCF1.
Constitutive overexpression of LrABCF1 in petunia (Petunia * hybrida) resulted in
an impairment of plant growth and development. LrABCF1 overexpression conferred
reduced susceptibility to CMV, Tobacco rattle virus (TRV), and B. cinerea
infection in transgenic petunia plants, accompanying by elevated transcripts of
PhGCN2 and a few defense-related genes in SA-signaling pathway. Our data indicate
that LrABCF1 positively modulates viral and fungal resistance.
PMID- 27485643
TI - The chronology of third molar mineralization by digital orthopantomography.
AB - The present study was designed to determine the chronology of third molar
mineralization to establish Indian reference data and to observe the advantages
of digital orthopantomography. Therefore, a cross-sectional study was undertaken
by evaluating 167 digital orthopantomographs in order to assess the
mineralization status of the mandibular third molar of Caucasian individuals (85
males and 82 females) between the age of 14 and 24. The evaluation was carried
out using the 8-stage developmental scheme of Demirjian et al (1973). The range,
mean age, standard deviation and Student t-test are presented for each stage of
mineralization in all four quadrants. Statistically significant differences
between males and females were not found for all four third molars. All the
individuals in this study with mature third molar were at least 18 years of age.
For medicolegal purposes, the likelihood of whether an Indian is older than 18
years or not was determined. The advantage of digital orthopantomography in the
interpretation of the tooth mineralization over the traditional method was
acknowledged.
PMID- 27485642
TI - Development of a Flow-Through USP-4 Apparatus Drug Release Assay to Evaluate
Doxorubicin Liposomes.
AB - Doxil(r) is a complex parenteral doxorubicin (DOX) liposome formulation approved
by the FDA. For generic doxorubicin liposomes, analyzing the release profile of
DOX is important for quality control and comparability studies. However, there is
no robust standard drug release assay available for doxorubicin liposomes. In
this study, we describe a USP-4 apparatus assay capable of discriminating DOX
liposomal formulations based on release profile. Establishment of the assay was
hindered by limited DOX release from liposomes in physiological conditions at 37
degrees C. The addition of NH4HCO3 to the release media facilitated DOX release
proportionally to the salt concentration added but caused precipitation of
released drug in USP-4 apparatus. Precipitation of DOX was avoided by adding
hydroxypropyl-cyclodextrin (HP-CD) to the release medium. We optimized conditions
for DOX release by varying a number of parameters such as: concentration of HP
CD, testing temperature, and concentration of tested samples. The optimized
release medium contained: 100 mM NH4HCO3, 75 mM 2-(N-morpholino) ethanesulfonic
acid (MES) and 5% w/v HP-CD, 5% w/v sucrose, 0.02% w/v NaN3 (pH 6). The drug
release assay was performed at 45 degrees C. The optimized release assay can
discriminate between DOX liposomal formulations of different compositions,
physicochemical properties, and prepared by different manufacturing methods. This
indicates that the assay could be used to compare DOX release from generic DOX
formulations to the innovator product Doxil(r).
PMID- 27485645
TI - Complications and Anesthesia for Colonoscopy: Culprit or Accomplice?
PMID- 27485646
TI - Limitations to an Important Study on the Risks of Colonoscopy With Anesthesia
Services.
PMID- 27485647
TI - Long-term Retention of Plastic Bread Bag Clip That Grips and Perforates the
Colonic Mucosa.
PMID- 27485648
TI - Rectal Indomethacin for the Prevention of Post-ERCP Pancreatitis.
PMID- 27485649
TI - Rectal Indomethacin for Post-ERCP Pancreatitis Prophylaxis in Average Risk
Patients: Too Early to Terminate and Too Early to Conclude.
PMID- 27485650
TI - Painful Anterior Chest Wall Mass, Compatible With Abscess on Computed Tomography
and Possible Osteomyelitis in a Man With Ulcerative Colitis.
PMID- 27485651
TI - Forward Progress of Sedation for Gastrointestinal Endoscopy Requires Taking a
Step Back.
PMID- 27485652
TI - A Rare Cause of Gastrointestinal Ulcers.
PMID- 27485653
TI - Anesthesia Services Increase Risk Of Complications After Colonoscopy: We Are Not
Sure!
PMID- 27485654
TI - Anesthesia's Impact on Outcomes After Endoscopy: More Research Is Needed.
PMID- 27485655
TI - Anesthesia Services Are Beneficial for Colonoscopy in Interventional
Gastroenterology.
PMID- 27485656
TI - Protein glycation and aggregation inhibitory potency of biomolecules from black
gram milled by-product.
AB - BACKGROUND: Persistent hyperglycaemia causes increased advanced glycation end
products (AGEs), which contribute to the pathogenesis of diabetic complication.
Therefore, effect of black gram milled by-product (BGBP) extract on inhibition of
AGE formation in a bovine serum albumin (BSA)/glucose system was investigated.
RESULTS: BGBP extract had a total polyphenol content of 82 mg GAE g-1 and
flavonoid content of 46 mg CE g-1 . Ferulic acid, protocatechuic acid, gallic
acid, gentisic acid, isovitexin, vitexin and epicatechin were the major
bioactives in the extract. BGBP extract exhibited an effective Fe2+ chelating
activity. Size exclusion-high-performance liquid chromatographic studies
indicated that upon BSA-AGE formation the BSA monomer content was 38%; however,
in the presence of BGBP extract at 50 and 100 ug levels, the monomer content
increased and it was found to be 48% and 73%, respectively. BGBP extract at 50
and 100 ug levels decreased the protein carbonyl and fructosamine contents, and
quenched the fluorescence intensity of glycated BSA in a dose-dependent manner.
Further, fluorescence and transmission electron microscopic studies confirmed the
decrease in formation of AGEs by BGBP extract. CONCLUSION: As BGBP extract
inhibited the formation of AGEs, the extract can be used as a nutraceutical or it
can be incorporated into food products to obtain functional foods. (c) 2016
Society of Chemical Industry.
PMID- 27485657
TI - Nicotine produces long-term increases in cocaine reinforcement in adolescent but
not adult rats.
AB - Studies have shown that many smokers begin using nicotine during adolescence, yet
the influence of early nicotine use on the response to other drugs of abuse in
adulthood is not fully understood. In the current study, nicotine was
administered to adolescent and adult rats for seven days. Thirty days later,
cocaine-induced locomotor activity and cocaine self-administration were examined
when the rats pretreated as adolescents were adults. Rats exposed to nicotine
during early adolescence were sensitized thirty days later to the locomotor
activating effects of cocaine and self-administered a greater number of cocaine
infusions than adolescent rats pretreated with vehicle. As a result of this
increased intake, the cocaine self-administration dose-response curve was shifted
upward indicating an increase in cocaine reinforcement. Rats pretreated with
nicotine as adults, however, did not show a difference in locomotor activity or
cocaine self-administration thirty days later compared to adult rats pretreated
with vehicle. These findings suggest that early exposure to nicotine has long
term consequences on cocaine use. These data further suggest that nicotine use
may carry a greater risk during adolescence than adulthood and adolescents who
smoke may be particularly vulnerable to stimulant use. This article is part of a
Special Issue entitled SI: Adolescent plasticity.
PMID- 27485658
TI - Anxiety modulates cognitive deficits in a perinatal glutathione deficit animal
model of schizophrenia.
AB - In this study, we investigated long-term repercussion of early glutathione
deficit by l-buthionine-(S,R)-sulfoximine (BSO) injections as a rat model of
schizophrenia. BSO rats were tested through various behavioral tasks requiring
animals to take into account previously delivered information. We showed that
relative to controls, BSO rats (1) were less active and more anxious in an
Elevated Plus Maze test, allowing us to split them into two subgroups with high
and low anxiety levels; (2) demonstrated normal abilities of behavioral
flexibility tested with a rat-adapted version of the Wisconsin Card Sorting Test
(WCST), with even higher abilities in anxious BSO rats suggesting reduced
interference of previously acquired rules; (3) did not forage normally in radial
arm mazes and mainly used clockwise strategies; (4) exhibited a lack of
habituation during a startle response task; and (5) showed a normal prepulse
inhibition of the startle response (PPI) and a normal conditioned taste aversion
(CTA). All these results indicate that early glutathione deficit provokes
persistent changes in adulthood and improves the validity of this animal model of
schizophrenia. They further suggest difficulties binding temporally separated
events (WCST), except when the salience of this information is very strong (CTA).
We propose that the transient glutathione deficit during cerebral development
could alter a "cognitive binding" process in interaction with the emotional state
that could possibly account for the disruption of integrative function that
characterizes schizophrenia.
PMID- 27485659
TI - Cognitive MMN and P300 in mild cognitive impairment and Alzheimer's disease: A
high density EEG-3D vector field tomography approach.
AB - Precise preclinical detection of dementia for effective treatment and stage
monitoring is of great importance. Miscellaneous types of biomarkers, e.g.,
biochemical, genetic, neuroimaging, and physiological, have been proposed to
diagnose Alzheimer's disease (AD), the usual suspect behind manifested cognitive
decline, and mild cognitive impairment (MCI), a neuropathology prior to AD that
does not affect cognitive functions. Event related potential (ERP) methods
constitute a non-invasive, inexpensive means of analysis and have been proposed
as sensitive biomarkers of cognitive impairment; besides, various ERP components
are strongly linked with working memory, attention, sensory processing and motor
responses. In this study, an auditory oddball task is employed, to acquire high
density electroencephalograhy recordings from healthy elderly controls, MCI and
AD patients. The mismatch negativity (MMN) and P300 ERP components are then
extracted and their relationship with neurodegeneration is examined. Then, the
neural activation at these components is reconstructed using the 3D vector field
tomography (3D-VFT) inverse solution. The results reveal a decline of both ERPs
amplitude, and a statistically significant prolongation of their latency as
cognitive impairment advances. For the MMN, higher brain activation is usually
localized in the inferior frontal and superior temporal gyri in the controls.
However, in AD, parietal sites exhibit strong activity. Stronger P300 generators
are mostly found in the frontal lobe for the controls, but in AD they often shift
to the temporal lobe. Reduction in inferior frontal source strength and the
switch of the maximum intensity area to parietal and superior temporal sites
suggest that these areas, especially the former, are of particular significance
when neurodegenerative disorders are investigated. The modulation of MMN and P300
can serve to produce biomarkers of dementia and its progression, and brain
imaging can further contribute to the diagnostic efficiency of ERPs.
PMID- 27485661
TI - Lack of Dependence of Indian Summer Monsoon Rainfall Extremes on Temperature: An
Observational Evidence.
AB - The intensification of precipitation extremes in a warming world has been
reported on a global scale and is traditionally explained with the Clausius
Clapeyron (C-C) relation. The relationship is observed to be valid in mid
latitudes; however, the debate persists in tropical monsoon regions, with the
extremes of the Indian Summer Monsoon Rainfall (ISMR) being a prime example.
Here, we present a comprehensive study on the dependence of ISMR extremes on both
the 2 m surface air temperature over India and on the sea surface temperature
over the tropical Indian Ocean. Remarkably, the ISMR extremes exhibit no
significant association with temperature at either spatial scale: neither
aggregated over the entire India/Tropical Indian Ocean area nor at the grid
levels. We find that the theoretical C-C relation overestimates the positive
changes in precipitation extremes, which is also reflected in the Coupled Model
Intercomparison Project 5 (CMIP5) simulations. We emphasize that the changing
patterns of extremes over the Indian subcontinent need a scientific re
evaluation, which is possible due to availability of the unique long-term in-situ
data. This can aid bias correction of model projections of extremes whose value
for climate adaptation can hardly be overemphasized, especially for the
developing tropical countries.
PMID- 27485660
TI - Incubation of food craving is independent of macronutrient composition.
AB - Cues previously paired with rewarding stimuli induce a time-dependent increase in
the motivational craving state (incubation of craving). Whether there is an
increase in craving for high-fat (HF) food over time, which may contribute to
overeating and obesity, has not been determined. We hypothesized that cues paired
with HF pellets would elicit a greater incubation of craving effect than those
paired with standard chow (SC) pellets. Rats exposed to cues associated with
either HF or SC pellets demonstrated equivalent levels of craving over an
abstinence period of 30 days. Diet preference tests between SC pellets and
LabDiet revealed that SC pellets were preferred over LabDiet. Rats reared on SC
pellets exclusively, did not display incubation of craving for SC pellets,
suggesting that prior history with the food plays an important role in cue
induced seeking behavior. Results identified cues previously associated with food
undergo a comparable magnitude of incubation of craving. When ingestive behavior
was measured after 30 days of abstinence, rats significantly increased their
consumption of HF pellets. Our results indicate that food cues gain importance
over time, trigger increased approach behaviors, and increased consumption of HF
food following abstinence. This may contribute to overeating and the development
of obesity.
PMID- 27485663
TI - Using Marginal Structural Modeling for Grade Retention Effects.
AB - Vandecandelaere, Vansteelandt, De Fraine, and Van Damme (this issue) described
marginal structural modeling (MSM) and used it to estimate the effects of a time
varying intervention, retention (holding back) in school grades, on students'
math achievement. This commentary supplements Vandecandelaere et al. (this issue)
and discusses several topics in retention studies and MSM. First, we discuss the
importance of equating time-varying confounders in retention studies. Second, we
discuss same-grade and same-age comparisons in retention studies. Third, we
discuss one important section in the authors' overview of MSM: why standard
methods (e.g., ANCOVA, propensity score analysis) cannot properly adjust for time
varying confounders. Finally, using the grade retention analyses in
Vandecandelaere et al. (this issue) as an example, we provide our insights on
four aspects of MSM: (a) covariate selection, (b) estimation of weights,
PMID- 27485665
TI - Proceedings of the International Summit on Emergency Medicine and Trauma 2014.
PMID- 27485662
TI - Intracellular Salmonella induces aggrephagy of host endomembranes in persistent
infections.
AB - Xenophagy has been studied in epithelial cells infected with Salmonella enterica
serovar Typhimurium (S. Typhimurium). Distinct autophagy receptors target this
pathogen to degradation after interacting with ubiquitin on the surface of
cytosolic bacteria, and the phagophore- and autophagosome-associated protein
MAP1LC3/LC3. Glycans exposed in damaged phagosomal membranes and diacylglycerol
accumulation in the phagosomal membrane also trigger S. Typhimurium xenophagy.
How these responses control intraphagosomal and cytosolic bacteria remains poorly
understood. Here, we examined S. Typhimurium interaction with autophagy in
fibroblasts, in which the pathogen displays limited growth and does not escape
into the cytosol. Live-cell imaging microscopy revealed that S. Typhimurium
recruits late endosomal or lysosomal compartments that evolve into a membranous
aggregate connected to the phagosome. Active dynamics and integrity of the
phagosomal membrane are requisite to induce such aggregates. This membranous
structure increases over time to become an aggresome that engages autophagy
machinery at late infection times (> 6 h postentry). The newly formed
autophagosome harbors LC3 and the autophagy receptor SQSTM1/p62 but is devoid of
ubiquitin and the receptor CALCOCO2/NDP52. Live-cell imaging showed that this
autophagosome captures and digests within the same vacuole the aggresome and some
apposed intraphagosomal bacteria. Other phagosomes move away from the aggresome
and avoid destruction. Thus, host endomembrane accumulation resulting from
activity of intracellular S. Typhimurium stimulates a novel type of aggrephagy
that acts independently of ubiquitin and CALCOCO2, and destroys only a few
bacteria. Such selective degradation might allow the pathogen to reduce its
progeny and, as a consequence, to establish persistent infections.
PMID- 27485664
TI - A meta-analysis of reflux genome-wide association studies in 6750 Northern
Europeans from the general population.
AB - BACKGROUND: Gastroesophageal reflux disease (GERD), the regurgitation of gastric
acids often accompanied by heartburn, affects up to 20% of the general
population. Genetic predisposition is suspected from twin and family studies but
gene-hunting efforts have so far been scarce and no conclusive genome-wide study
has been reported. We exploited data available from general population samples,
and studied self-reported reflux symptoms in relation to genome-wide single
nucleotide polymorphism (SNP) genotypes. METHODS: We performed a GWAS meta
analysis of three independent population-based cohorts from Sweden, Finland, and
UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using
questionnaire-derived symptom data. Upon stringent quality controls, genotype
data for more than 2.5M markers were used for association testing. Bioinformatic
characterization of genomic regions associated with GERD included gene-set
enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene
expression, and computational analysis of drug-induced gene expression signatures
using Connectivity Map (cMap). KEY RESULTS: We identified 30 GERD suggestive risk
loci (P<=5*10-5 ), with concordant risk effects in all cohorts, and predicted
functional effects on gene expression in relevant tissues. GSEA revealed
involvement of GERD risk genes in biological processes associated with the
regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had
significant effects on GERD risk gene expression, while antituberculosis and anti
inflammatory drugs scored highest among the repurposed compounds. CONCLUSIONS: We
report a large-scale genetic study of GERD, and highlight genes and pathways that
contribute to further our understanding of its pathogenesis and therapeutic
opportunities.
PMID- 27485666
TI - A Semi-Supervised Learning Approach to Enhance Health Care Community-Based
Question Answering: A Case Study in Alcoholism.
AB - BACKGROUND: Community-based question answering (CQA) sites play an important role
in addressing health information needs. However, a significant number of posted
questions remain unanswered. Automatically answering the posted questions can
provide a useful source of information for Web-based health communities.
OBJECTIVE: In this study, we developed an algorithm to automatically answer
health-related questions based on past questions and answers (QA). We also aimed
to understand information embedded within Web-based health content that are good
features in identifying valid answers. METHODS: Our proposed algorithm uses
information retrieval techniques to identify candidate answers from resolved QA.
To rank these candidates, we implemented a semi-supervised leaning algorithm that
extracts the best answer to a question. We assessed this approach on a curated
corpus from Yahoo! Answers and compared against a rule-based string similarity
baseline. RESULTS: On our dataset, the semi-supervised learning algorithm has an
accuracy of 86.2%. Unified medical language system-based (health related)
features used in the model enhance the algorithm's performance by proximately 8%.
A reasonably high rate of accuracy is obtained given that the data are
considerably noisy. Important features distinguishing a valid answer from an
invalid answer include text length, number of stop words contained in a test
question, a distance between the test question and other questions in the corpus,
and a number of overlapping health-related terms between questions. CONCLUSIONS:
Overall, our automated QA system based on historical QA pairs is shown to be
effective according to the dataset in this case study. It is developed for
general use in the health care domain, which can also be applied to other CQA
sites.
PMID- 27485667
TI - The sex locus is tightly linked to factors conferring sex-specific lethal effects
in the mosquito Aedes aegypti.
AB - In many taxa, sex chromosomes are heteromorphic and largely non-recombining.
Evolutionary models predict that spread of recombination suppression on the Y
chromosome is fueled by the accumulation of sexually antagonistic alleles in
close linkage to the sex determination region. However, empirical evidence for
the existence of sexually antagonistic alleles is scarce. In the mosquito Aedes
aegypti, the sex-determining chromosomes are homomorphic. The region of
suppressed recombination, which surrounds the male-specific sex-determining gene,
remains very small, despite ancient origin of the sex chromosomes in the Aedes
lineage. We conducted a genetic analysis of the A. aegypti chromosome region
tightly linked to the sex locus. We used a strain with an enhanced green
fluorescent protein (EGFP)-tagged transgene inserted near the male-determining
gene to monitor crossing-over events close to the boundary of the sex-determining
region (SDR), and to trace the inheritance pattern of the transgene in relation
to sex. In a series of crossing experiments involving individuals with a
recombinant sex chromosome we found developmental abnormalities leading to 1:2
sex biases, caused by lethality of half of the male or female progeny. Our
results suggest that various factors causing sex-specific lethal effects are
clustered within the neighborhood of the SDR, which in the affected sex are
likely lost or gained through recombination, leading to death. These may include
genes that are recessive lethal, vital for development and/or sexually
antagonistic. The sex chromosome fragment in question represents a fascinating
test case for the analysis of processes that shape stable boundaries of a non
recombining region.
PMID- 27485668
TI - Genome-wide SNP data suggest complex ancestry of sympatric North Pacific killer
whale ecotypes.
AB - Three ecotypes of killer whale occur in partial sympatry in the North Pacific.
Individuals assortatively mate within the same ecotype, resulting in correlated
ecological and genetic differentiation. A key question is whether this pattern of
evolutionary divergence is an example of incipient sympatric speciation from a
single panmictic ancestral population, or whether sympatry could have resulted
from multiple colonisations of the North Pacific and secondary contact between
ecotypes. Here, we infer multilocus coalescent trees from >1000 nuclear single
nucleotide polymorphisms (SNPs) and find evidence of incomplete lineage sorting
so that the genealogies of SNPs do not all conform to a single topology. To
disentangle whether uncertainty in the phylogenetic inference of the
relationships among ecotypes could also result from ancestral admixture events we
reconstructed the relationship among the ecotypes as an admixture graph and
estimated f4-statistics using TreeMix. The results were consistent with episodes
of admixture between two of the North Pacific ecotypes and the two outgroups
(populations from the Southern Ocean and the North Atlantic). Gene flow may have
occurred via unsampled 'ghost' populations rather than directly between the
populations sampled here. Our results indicate that because of ancestral
admixture events and incomplete lineage sorting, a single bifurcating tree does
not fully describe the relationship among these populations. The data are
therefore most consistent with the genomic variation among North Pacific killer
whale ecotypes resulting from multiple colonisation events, and secondary contact
may have facilitated evolutionary divergence. Thus, the present-day populations
of North Pacific killer whale ecotypes have a complex ancestry, confounding the
tree-based inference of ancestral geography.
PMID- 27485669
TI - Relaxed selective constraints drove functional modifications in peripheral
photoreception of the cavefish P. andruzzii and provide insight into the time of
cave colonization.
AB - The genetic basis of phenotypic changes in extreme environments is a key but
rather unexplored topic in animal evolution. Here we provide an exemplar case of
evolution by relaxed selection in the Somalian cavefish Phreatichthys andruzzii
that has evolved in the complete absence of light for at least 2.8 million years.
This has resulted in extreme degenerative phenotypes, including complete eye loss
and partial degeneration of the circadian clock. We have investigated the
molecular evolution of the nonvisual photoreceptor melanopsin opn4m2, whose
mutation contributes to the inability of peripheral clocks to respond to light.
Our intra- and inter-species analyses suggest that the 'blind' clock in P.
andruzzii evolved because of the loss of selective constraints on a trait that
was no longer adaptive. Based on this change in selective regime, we estimate
that the functional constraint on cavefish opn4m2 was relaxed at ~5.3 Myr. This
implies a long subterranean history, about half in complete isolation from the
surface. The visual photoreceptor rhodopsin, expressed in the brain and
implicated in photophobic behavior, shows similar evolutionary patterns,
suggesting that extreme isolation in darkness led to a general weakening of
evolutionary constraints on light-responsive mechanisms. Conversely, the same
genes are still conserved in Garra barreimiae, a cavefish from Oman, that
independently and more recently colonized subterranean waters and evolved
troglomorphic traits. Our results contribute substantially to the open debate on
the genetic bases of regressive evolution.
PMID- 27485670
TI - "It's Like Moving the Titanic:" Community Organizing to Address Food
(In)Security.
AB - Health communication scholars are uniquely positioned to examine the ways in
which individuals organize to address current and future exigencies related to
social ills. In particular, organizations are key sites in understanding our
health decisions related to food choice. From a young age, children develop
habits of eating that stay with them throughout their life. More specifically,
food insecurity impacts childhood nutrition. Children from low-income homes
experience disproportional negative health outcomes. Appalachian Ohio is an area
within the United States that experiences severe poverty. In 2013, community
members in a small public school district in Appalachian Ohio formed the
Appalachian Nutrition Advisory Council to address the nutritional needs of
students in schools. This project stories the ways in which community members
creatively organized to supplement existing structures in place designed to
address school nutrition and food security.
PMID- 27485671
TI - Direct observation of slow intersystem crossing in an aromatic ketone,
fluorenone.
AB - Direct measurements of Single vibronic Level InterSystem Crossing (SLISC) have
been performed on the fluorenone molecule in the gas phase, by time resolved
photoelectron and photoion spectroscopy. Vibronic transitions above the S1 npi*
origin were excited in the 432-420 nm region and the decay of S1 and growth of
T1(3)pipi* could be observed within a 10 ns time domain. The ionization potential
is measured as 8.33 +/- 0.04 eV. The energy of the first excited triplet state of
fluorenone, T1 has been characterized directly at 18 640 +/- 250 cm(-1). The
internal conversion of S1 to S0 is found to amount to ~15% of the population
decay, thus ISC is the dominant electronic relaxation process. ISC, although
favored by the S1(1)npi*-T1(3)pipi* coupling scheme, is 3 orders of magnitude
less efficient than in the similar molecule benzophenone. Thus, the planarity of
the fluorenone molecule disfavors the exploration of the configuration space
where surface crossings would create high ISC probability, which occurs in
benzophenone through surface crossings. The time evolution of S1 fluorenone is
well accounted for by the statistical decay of individual levels into a quasi
continuum of T1 vibronic levels.
PMID- 27485672
TI - MCRS1: Not only ran.
PMID- 27485673
TI - Metal Oleate Induced Etching and Growth of Semiconductor Nanocrystals, Nanorods,
and Their Heterostructures.
AB - Unexpected etching of nanocrystals, nanorods, and their heterostructures by one
of the most commonly used metal precursors, metal oleates, is reported. Zn oleate
is shown to etch CdS nanorods anisotropically, where the length decreases without
a significant change in the diameter. Sodium oleate enhances the etch rate,
whereas oleic acid alone does not cause etching, indicating the importance of the
countercation on the rate of oleate induced etching. Subsequent addition of Se
precursors to the partially etched nanorods in Zn oleate solution can lead to
epitaxial growth of CdSe particles rather than the expected ZnSe growth, despite
an excess amount of Zn precursors being present. The composition of this
epitaxial growth can be varied from CdSe to ZnSe, depending on the amount of
excess oleic acid or the reaction temperature. Similar tuning of composition can
be observed when starting with collinear CdSe/CdS/CdSe rod/rod/rod
heterostructures and spherical CdS (or CdSe/CdS core/shell) nanocrystals.
Conversion of collinear rod/rod/rod structures to barbells and interesting rod
growth from nearly spherical particles among other structures can also result due
to the initial etching effect of metal oleates. These observations have important
implications on our understanding of nanocrystal heterostructure synthesis and
open up new routes to varying the composition and morphology of these materials.
PMID- 27485674
TI - Risk Factors for Falls in People With a Lower Limb Amputation: A Systematic
Review.
AB - OBJECTIVE: To review the evidence connecting risk factors to falls in adults with
a lower limb amputation (LLA) across the continuum of care settings. DESIGN:
Systematic review. LITERATURE SURVEY: Electronic database searches were conducted
in MEDLINE, Pubmed, CINAHL, and EMBASE covering January 1988 to January 2016.
Noninterventional studies, including cohort and cross-sectional studies, were
included. Two reviewers independently completed data extraction and quality
evaluation. METHODOLOGY: Twelve studies met the inclusion criteria and quality of
reporting was evaluated using the criteria by Tooth et al. SYNTHESIS: The average
quality of reporting score was 19.8, scores ranged from 16 to 29. Studies covered
the acute hospital stay after the amputation, inpatient rehabilitation, and
community living. Falls were a common occurrence, with the cohort studies
reporting 20.8% for acute hospital stay to 58% in the community years after the
amputation. Injurious falls also were common, with an occurrence ranging from 40%
to 60%. Risk factors that increase falls and are shared with the general
population of older adults include lower extremity muscle weakness, increasing
age, comorbidities, and number of prescription medications. Risk factors for
falls that are unique to adults with LLA are dysvascular etiology of the
amputation, transtibial level of amputation in the postoperative period and
transfemoral level postrehabilitation, and reduced sense of vibration.
CONCLUSIONS: Falls in adults with an LLA are common from the time of the
amputation to years later living in the community. Risk factors vary across care
settings after the amputation, which has implications for safety and fall
prevention strategies. LEVEL OF EVIDENCE: III.
PMID- 27485675
TI - Relationships Between Age at Menarche, Walking Gait Base of Support, and Stance
Phase Frontal Plane Knee Biomechanics in Adolescent Girls.
AB - BACKGROUND: Age at menarche impacts patterns of pubertal growth and skeletal
development. These effects may carry over into variation in biomechanical
profiles involved in sports-related traumatic and overuse knee injuries. The
present study investigated whether age at menarche is a potential indicator of
knee injury risk through its influence on knee biomechanics during normal
walking. OBJECTIVE: To test the hypothesis that earlier menarche is related to
postpubertal biomechanical risk factors for knee injuries, including a wider,
more immature gait base of support, and greater valgus knee angles and moments.
DESIGN: Cross-sectional observational study. SETTING: University research
facility. PARTICIPANTS: Healthy, postmenarcheal, adolescent girls. METHODS: Age
at menarche was obtained by recall questionnaire. Pubertal growth and
anthropometric data were collected by using standard methods. Biomechanical data
were taken from tests of walking gait at self-selected speed. Reflective marker
position data were collected with a 3-dimensional quantitative motion analysis
system, and 3 force plates recorded kinetic data. MAIN OUTCOME MEASURES: Age at
menarche; growth and anthropometric measurements; base of support; static knee
frontal plane angle; and dynamic knee frontal plane angles and moments during
stance. RESULTS: Earlier menarche was correlated significantly with abbreviated
pubertal growth and postpubertal retention of immature traits, including a wider
base of support. Earlier menarche and wider base of support were both correlated
with more valgus static knee angles, more valgus knee abduction angles and
moments at foot-strike, and a more valgus peak knee abduction angle during
stance. Peak knee abduction moment during stance was not correlated with age at
menarche or base of support. CONCLUSIONS: Earlier menarche and its effects on
growth are associated with retention of a relatively immature gait base of
support and a tendency for static and dynamic valgus knee alignment. This
biomechanical profile may put girls with earlier menarche at greater risk for
sports-related knee injuries. LEVEL OF EVIDENCE: Not applicable.
PMID- 27485676
TI - Melorheostosis: A Retrospective Clinical Analysis of 24 Patients at the Mayo
Clinic.
AB - BACKGROUND: Current understanding of the clinical features of persons with
melorheostosis is restricted primarily to individual case reports and small case
series. OBJECTIVE: To assess the clinical features of patients with
melorheostosis treated at our institution from 1972 through 2010. DESIGN: Chart
review. SETTING: Tertiary academic medical center. PARTICIPANTS: Twenty-three
patients with "definite" and one patient with "probable" melorheostosis based on
radiographic criteria. METHODS: The eligible study cohort was identified through
the Rochester Medical Index database. Further diagnostic confirmation of patients
with melorheostosis was performed by radiographic review. MAIN OUTCOME
MEASUREMENTS: We evaluated age at first visit to our institution, gender,
affected body area, number of bones affected, presenting symptoms, surgical
evaluation, and therapies provided. RESULTS: The average age at first evaluation
at our clinic was 36.5 years (median 41.5 years, range 3-68 years). The female to
male ratio was 4:1. The lower extremity was most commonly affected (66.6%),
followed by upper extremity (33.3%), spine (16.6%), and head (8.3%). One-third of
patients had involvement of a single bone; two-thirds had multiple bone
involvement. Pain was the most common presenting concern (83.3%), followed by
deformity (54.1%), limitation of movement (45.8%), numbness (37.5%), and weakness
(25.0%). Most patients had a physician evaluation (87.5%); patients also
underwent orthopedic surgery (45.8%), physical therapy (33.3%), and occupational
therapy (12.5%). CONCLUSIONS: Melorheostosis is a rare sclerotic bone disease
resulting in pain, deformity, and dysfunction. An interdisciplinary approach to
care should include nonoperative and operative evaluation, as well as appropriate
therapies. A prospective approach to evaluation, including imaging and physical
examinations, would provide valuable longitudinal data. LEVEL OF EVIDENCE: IV.
PMID- 27485677
TI - Insights from complex aortic surgery with a Streamliner device for aortic arch
repair (STAR).
AB - OBJECTIVE: Aortic arch aneurysms and thoracoabdominal aortic arch aneurysms are
technically challenging to manage by established surgical and endovascular
methods. The Streamliner Multilayer Flow Modulator device (Cardiatis, Isnes,
Brussels, Belgium) offers an unorthodox option for these high-risk cases. The
Streamliner device for aortic arch repair (STAR) study investigated complex
aneurysm cases managed by the Streamliner Multilayer Flow Modulator device and
offers an analytic solution for a clinical dilemma. METHODS: Six cases were
included, with a 1-year follow-up, comprising 4 pure arch aneurysms and 2
thoracoabdominal aortic arch aneurysms Crawford type I, from a multicenter
database hosted by the Streamliner Multilayer Flow Modulator Global Registry. A
total of 50% of cases were performed under instructions for use. All were
American Society of Anesthesiology IV and originated from zone 0. All cases were
computationally analyzed, which consisted of (1) simulating the treatment on the
basis of the postoperative data, (2) repositioning the stents for the failed
technical cases, and (3) assessing the effects of overlapping devices on branch
patency. RESULTS: Correct device placement induced aneurysm flow streamlining,
which reduced the dynamic pressure by 23% to 66%, whereas incorrect placements
promoted Failure Mode I with 58% and 16% dynamic pressure increases and aneurysm
volume expansion up to 23%. Overlapped devices improved distal perfusion by
increasing arch branch outflows from 5% to 24%. The Streamliner Multilayer Flow
Modulator device does not benefit a sac volume greater than 400 cm3. CONCLUSIONS:
The Streamliner Multilayer Flow Modulator device is a new technology that can
manage complex aortic arch aneurysms and thoracoabdominal aortic arch aneurysms
with favorable clinical outcomes if it is performed under instructions for use.
Careful procedure planning and perioperative virtual stent placement will avoid
foreshortening, prevent inadequate stent overlap lengths, and provide insight
into the sufficient numbers of required implanted devices.
PMID- 27485678
TI - Off-pump coronary artery bypass grafting: Do it often, do it well, and do it
completely-or don't do it at all.
PMID- 27485679
TI - Stapled aortic graft-to-graft anastomoses: Is automation optimization?
PMID- 27485680
TI - The latissimus dorsi flap continues to play an important role in cardiothoracic
surgery.
PMID- 27485681
TI - Oilfield water treatment by electrocoagulation-reverse osmosis for agricultural
use: effects on germination and early growth characteristics of sunflower.
AB - This study aims to evaluate the effects of oilfield water (OW), treated by a
hybrid process of electrocoagulation and reverse osmosis (EC-RO), on seed
germination and early growth characteristics of sunflower (Heliantus annus L.).
In the EC step, tests were conducted with 28.6 A m-2 current density and 4 min.
reaction time. In the RO step, the system was operated with 1 L min-1 constant
flow and 2 MPa, 2.5 MPa and 3 MPa feed pressures. In all feed pressures, RO
polymeric membranes achieved very high removals of chemical oxygen demand (up to
89%) and oils and greases (100%) from EC-treated effluent. In best feed pressure
(2.5 MPa), turbidity, total dissolved salts, electrical conductivity, salinity,
toxic ions and sodium adsorption ratio values attained internationally recognized
standards for irrigation water. Using EC-RO (feed pressure:2.5 MPa) treated OW,
germinated sunflower seeds percentage (86 +/- 6%), speed of germination (30 +/-
2) and biomass production (49 +/- 5 mg) were statistically similar to control
(distilled water) results. Vigor index average values obtained using OW treated
by EC-RO (3871)were higher than that obtained by OW water treated by EC (3300).
The results of this study indicate that EC-RO seems to be a promising alternative
for treatment of OW aiming sunflower crops irrigation, since the use of this
treated effluent did not affect adversely seed germination and seedling
development, and improved seedling vigor. Furthermore, OW treatment by EC-RO
reduces sodium levels into acceptable standards values avoiding soil degradation.
PMID- 27485682
TI - Path to health asthma study: A survey of pediatric asthma in an urban community.
AB - OBJECTIVE: Minority children with asthma who live in low-income urban communities
bear a disproportionate burden of the disease. This study explores the perceived
health care needs related to asthma care, identifies asthma triggers, potential
barriers to care, and assesses the need for additional community resources.
METHODS: We conducted a cross-sectional survey of Hispanic and African American
adults (n = 53) who take care of a child with asthma and live in an urban
community of North Philadelphia. Input from community leaders was obtained in the
development the survey tool resulting in a unique 'community-centric'
questionnaire. The survey was also available in Spanish. All surveys were
conducted in the community setting. RESULTS: Variables were used to measure
asthma severity and triggers. Children were categorized with intermittent (n =
24, 45.3%), mild persistent (n = 13, 24.5%), or moderate-to-severe persistent
asthma (n = 16, 30.2%). Most children with persistent asthma were enrolled under
Medicaid or CHIP (n = 24, p = 0.011) and reflected a low-income socioeconomic
status. Persistent asthma was found to be associated with most triggers: pets,
dust mites, mice, mold, and cockroaches. There was no significant association
between environmental tobacco smoke and persistent asthma. Children with
persistent asthma and 2 or more triggers were more likely to be hospitalized and
go to the Emergency Department. CONCLUSION: Urban minority children living in low
income communities face neighborhood-specific asthma triggers and challenges to
care. Studies conducted in urban neighborhoods, with collaboration from community
members, will highlight the need of comprehensive services to account for
community-centric social determinants.
PMID- 27485683
TI - Distinct beneficial effects of continuous vs accumulated exercise training on
cardiovascular risk factors in Wistar rats.
AB - We compared the effects of continuous exercise (CE) vs accumulated exercise (AE)
training on CVD risk factors and heart of young male Wistar rats. The exercise
training (ET) was performed in a swimming pool for 30-60 min/day, 5 days/week
over 15 weeks. CE group performed the ET in a single long daily session (30-60
min), while AE group performed the ET at the same frequency, intensity, and
duration of CE rats, but in three short bouts over the course of a day (10-20 min
in three daily sessions). AE training was more efficient than CE in attenuating
body and fat weight gain and inhibiting visceral adipocyte hypertrophy at the
same food intake level. CE training was more efficient in improving systolic
blood pressure, LDL/HDL cholesterol, and serum triglyceride. Both ET protocols
increased heart function, decreased lipid peroxidation, and increased
intracellular Hsp72 content in the heart. This work shows distinct beneficial
effects of CE vs AE training suggesting that the prescription of one or other may
be preferred to prevent the increase of a specific CVD risk factor.
PMID- 27485684
TI - Comparative thermal unfolding study of psychrophilic and mesophilic subtilisin
like serine proteases by molecular dynamics simulations.
AB - Molecular dynamics (MD) simulations of a subtilisin-like serine protease VPR from
the psychrophilic marine bacterium Vibrio sp. PA-44 and its mesophilic homologue,
proteinase K (PRK), have been performed for 20 ns at four different temperatures
(300, 373, 473, and 573 K). The comparative analyses of MD trajectories reveal
that at almost all temperatures, VPR exhibits greater structural
fluctuations/deviations, more unstable regular secondary structural elements, and
higher global flexibility than PRK. Although these two proteases follow similar
unfolding pathways at high temperatures, VPR initiates unfolding at a lower
temperature and unfolds faster at the same high temperatures than PRK. These
observations collectively indicate that VPR is less stable and more heat-labile
than PRK. Analyses of the structural/geometrical properties reveal that, when
compared to PRK, VPR has larger radius of gyration (Rg), less intramolecular
contacts and hydrogen bonds (HBs), more protein-solvent HBs, and smaller burial
of nonpolar area and larger exposure of polar area. These suggest that the
increased flexibility of VPR would be most likely caused by its reduced
intramolecular interactions and more favourable protein-solvent interactions
arising from the larger exposure of the polar area, whereas the enhanced
stability of PRK could be ascribed to its increased intramolecular interactions
arising from the better optimized hydrophobicity. The factors responsible for the
significant differences in local flexibility between these two proteases were
also analyzed and ascertained. This study provides insights into molecular basis
of thermostability of homologous serine proteases adapted to different
temperatures.
PMID- 27485685
TI - Stress and resilience in a post-Francis world - a qualitative study of executive
nurse directors.
AB - AIMS: The aim of this study was to explore the role stressors experienced by
executive nurse directors and strategies employed to maintain resilience.
BACKGROUND: Recent financial pressures on and care quality scandals in the UK NHS
impact on the work of executive nurse directors. The short length of tenure and
the high number of vacancies for these posts point to the exacting demands of the
role and raise questions about the support mechanisms available for the most
senior nurses in NHS organizations. DESIGN: A grounded constructivist study.
METHODS: Semi-structured telephone interviews conducted between February-July,
2014. RESULTS: Stressors were both chronic (workload, lack of corporate
responsibility for quality, reductions in quality team staffing, tensions between
financial solvency and care quality and personal vulnerability) and acute
(dealing with complaints and major incidents). Resilience required the support of
fellow executives, peers, family and mentors and could be enhanced by self
discipline, good preparation for the post and ongoing coaching. CONCLUSION:
Recent fiscal austerity and scandals relating to quality of care have increased
pressure on executive nurse directors. Increasing size of organizations, limited
resources devoted to quality combined with poorly defined limits of
responsibility are all major stressors and executive nurse directors, both in the
United Kingdom and internationally, need clear strategies to maintain resilience.
Repetitive demands for data by oversight organizations may detract from more
important quality assurance strategies.
PMID- 27485687
TI - Cross-talk Between Host, Microbiome and Probiotics: A Systems Biology Approach
for Analyzing the Effects of Probiotic Enterococcus faecium NCIMB 10415 in
Piglets.
AB - A comprehensive data-set from a multidisciplinary feeding experiment with the
probiotic Enterococcus faecium was analyzed to elucidate effects of the probiotic
on growing piglets. Sixty-two piglets were randomly assigned to a control (no
probiotic treatment) and a treatment group (E. faecium supplementation). Piglets
were weaned at 26 d. Age-matched piglets were sacrificed for the collection of
tissue samples at 12, 26, 34 and 54 d. In addition to zootechnical data, the
composition and activity of intestinal microbiota, immune cell types, and
intestinal responses were determined. Our systems analysis revealed clear effects
on several measured variables in 26 and 34 days old animals, while response
patterns varied between piglets from different age groups. Correlation analyses
identified reduced associations between intestinal microbial communities and
immune system reactions in the probiotic group. In conclusion, the developed
model is useful for comparative analyses to unravel systems effects of dietary
components and their time resolution. The model identified that effects of E.
faecium supplementation most prominently affected the interplay between
intestinal microbiota and the intestinal immune system. These effects, as well as
effects in other subsystems, clustered around weaning, which is the age where
piglets are most prone to diarrhea.
PMID- 27485688
TI - Theoretical Studies on Pyrazolo[3,4-d]pyrimidine Derivatives as Potent Dual c
Src/Abl Inhibitors Using 3D-QSAR and Docking Approaches.
AB - In recent years, the development of dual or multi-targeted inhibitors has
captured extensive attention of research for treating of malignancies. In this
paper, three-dimensional quantitative structure-activity relationship and docking
studies were performed on 87 pyrazolo[3,4-d]pyrimidines as dual Src/Abl
inhibitors. The appropriate binding orientations and conformations of these
compounds interacting with both Src and Abl kinases were revealed by docking
studies, and the established optimum CoMFA models yielded q(2) =0.856, R(2)
=0.966 for Src and q(2) =0.869, R(2) =0.974 for Abl, and the best CoMSIA models
gave q(2) =0.877, R(2) =0.979 for Src and q(2) =0.885, R(2) =0.982 for Abl.
Systemic external validations further confirm the satisfactory predictive power
of these models, producing R(2) pred values of 0.872 and 0.865 for Src, 0.876 and
0.867 for Abl, r(2) m values of 0.832 and 0.928 for Src, 0.838 and 0.904 for Abl,
respectively. In addition, through a comparison between 3D-QSAR contour maps and
docking results, it is revealed that the hydrophobic and electrostatic
interactions of compounds play significant roles for the inhibitory activity
against both Src and Abl kinases. Some structural factors influencing the
activities of these compounds were discussed in detail. The key amino acids
impacting the receptor-ligand interactions have been identified. These
theoretical results can offer useful references for designing novel potential
dual Src/Abl inhibitors.
PMID- 27485686
TI - Neuronal Deletion of Kmt2a/Mll1 Histone Methyltransferase in Ventral Striatum is
Associated with Defective Spike-Timing-Dependent Striatal Synaptic Plasticity,
Altered Response to Dopaminergic Drugs, and Increased Anxiety.
AB - Lysine (K) methyltransferase 2a (Kmt2a) and other regulators of H3 lysine 4
methylation, a histone modification enriched at promoters and enhancers, are
widely expressed throughout the brain, but molecular and cellular phenotypes in
subcortical areas remain poorly explored. We report that Kmt2a conditional
deletion in postnatal forebrain is associated with excessive nocturnal activity
and with absent or blunted responses to stimulant and dopaminergic agonist drugs,
in conjunction with near-complete loss of spike-timing-dependent long-term
potentiation in medium spiny neurons (MSNs). Selective ablation of Kmt2a, but not
the ortholog Kmt2b, in adult ventral striatum/nucleus accumbens neurons markedly
increased anxiety scores in multiple behavioral paradigms. Striatal transcriptome
sequencing in adult mutants identified 262 Kmt2a-sensitive genes, mostly
downregulated in Kmt2a-deficient mice. Transcriptional repression includes the 5
Htr2a serotonin receptor, strongly associated with anxiety- and depression
related disorders in human and animal models. Consistent with the role of Kmt2a
in promoting gene expression, the transcriptional regulators Bahcc1, Isl1, and
Sp9 were downregulated and affected by H3K4 promoter hypomethylation. Therefore,
Kmt2a regulates synaptic plasticity in striatal neurons and provides an
epigenetic drug target for anxiety and dopamine-mediated behaviors.
PMID- 27485689
TI - The Development of Novel Chemical Fragment-Based Descriptors Using Frequent
Common Subgraph Mining Approach and Their Application in QSAR Modeling.
AB - We present a novel approach to generating fragment-based molecular descriptors.
The molecules are represented by labeled undirected chemical graph. Fast Frequent
Subgraph Mining (FFSM) is used to find chemical-fragments (subgraphs) that occur
in at least a subset of all molecules in a dataset. The collection of frequent
subgraphs (FSG) forms a dataset-specific descriptors whose values for each
molecule are defined by the number of times each frequent fragment occurs in this
molecule. We have employed the FSG descriptors to develop variable selection k
Nearest Neighbor (kNN) QSAR models of several datasets with binary target
property including Maximum Recommended Therapeutic Dose (MRTD), Salmonella
Mutagenicity (Ames Genotoxicity), and P-Glycoprotein (PGP) data. Each dataset was
divided into training, test, and validation sets to establish the statistical
figures of merit reflecting the model validated predictive power. The
classification accuracies of models for both training and test sets for all
datasets exceeded 75 %, and the accuracy for the external validation sets
exceeded 72 %. The model accuracies were comparable or better than those reported
earlier in the literature for the same datasets. Furthermore, the use of fragment
based descriptors affords mechanistic interpretation of validated QSAR models in
terms of essential chemical fragments responsible for the compounds' target
property.
PMID- 27485690
TI - Computational Search for Possible Mechanisms of 4-Thiazolidinones Anticancer
Activity: The Power of Visualization.
AB - Public databases of NCI-60 tumor cell line screen results and measurements of
molecular targets in the NCI-60 panel give the opportunity to assign possible
anticancer mechanism to compounds with positive outcome from antitumor assay.
Here, the novel protocol of NCI databases mining where inferences are based on
the visualization is presented and utilized with the aim to identify putative
biological routes of 4-thiazolidinones anticancer effect. As a result, highly
potent 4-thiazolidinone-pyrazoline-isatin conjugates show the similarity of
activity patterns with puromycin and CBU-028 and their pattern is also highly
correlated with fraction of methylated CpG sites in CD34, AF5q31 and SYK. Several
compounds from this group show strong negative correlation with fraction of
methylated CpG sites in HOXA5. Thiopyrano[2,3-d][1,3]thiazol-2-ones bearing
naphtoquinone fragment were found to possess the same activity pattern as
fusarubin does. But none of the studied 4-thiazolidinone derivatives has activity
fingerprint similar to standard anticancer agents. The obtained results bring
medicinal chemistry closer to the understanding of basic nature of 4
thiazolidinones effect on cancer cells.
PMID- 27485691
TI - Prediction of Signal Peptide Cleavage Sites with Subsite-Coupled and Template
Matching Fusion Algorithm.
AB - Fast and effective prediction of signal peptides (SP) and their cleavage sites is
of great importance in computational biology. The approaches developed to predict
signal peptide can be roughly divided into machine learning based, and sliding
windows based. In order to further increase the prediction accuracy and coverage
of organism for SP cleavage sites, we propose a novel method for predicting SP
cleavage sites called Signal-CTF that utilizes machine learning and sliding
windows, and is designed for N-termial secretory proteins in a large variety of
organisms including human, animal, plant, virus, bacteria, fungi and archaea.
Signal-CTF consists of three distinct elements: (1) a subsite-coupled and
regularization function with a scaled window of fixed width that selects a set of
candidates of possible secretion-cleavable segment for a query secretory protein;
(2) a sum fusion system that integrates the outcomes from aligning the cleavage
site template sequence with each of the aforementioned candidates in a scaled
window of fixed width to determine the best candidate cleavage sites for the
query secretory protein; (3) a voting system that identifies the ultimate signal
peptide cleavage site among all possible results derived from using scaled
windows of different width. When compared with Signal-3L and SignalP 4.0
predictors, the prediction accuracy of Signal-CTF is 4-12 %, 10-25 % higher than
that of Signal-3L for human, animal and eukaryote, and SignalP 4.0 for eukaryota,
Gram-positive bacteria and Gram-negative bacteria, respectively. Comparing with
PRED-SIGNAL and SignalP 4.0 predictors on the 32 archaea secretory proteins of
used in Bagos's paper, the prediction accuracy of Signal-CTF is 12.5 %, 25 %
higher than that of PRED-SIGNAL and SignalP 4.0, respectively. The predicting
results of several long signal peptides show that the Signal-CTF can better
predict cleavage sites for long signal peptides than SignalP, Phobius, Philius,
SPOCTOPUS, Signal-CF and Signal-3L. These results show that Signal-CTF is more
accurate and flexible in predicting signal peptides of different characteristics
for many organisms. Signal-CTF is freely available as a web-server at
http://darwin2.cbi.utsa.edu/minniweb/index.html.
PMID- 27485692
TI - Insights from QM/MM Modeling the 3D Structure of the 2009 H1N1 Influenza A Virus
Neuraminidase and Its Binding Interactions with Antiviral Drugs.
AB - Control of drug release through the inhibition of neuraminidase-1 has been
identified as a potential target for the treatment of H1N1 influenza; however,
the drug binding mode of neuraminidase is not yet completely understood. In this
work, we propose a model for a neuraminidase-1 complex based on four known X-ray
structures of drug/neuraminidase-1 complexes. Specifically, H1N1 neuraminidase-1
complexed with 4 drugs (zanamivir, laninamivir, laninamivir octanoate and
oseltamivir) was first investigated using a combined quantum mechanical and
molecular mechanical (QM/MM) approach. Based on these structures, a model for the
H1N1 neuraminidase-1 complex was proposed and simulated using the same
computational protocol. Implications to drug/H1N1 neuraminidase-1 binding modes
are discussed. From our simulations, the predicted binding free energies of the
four drugs are in good agreement with the experimental results, with the
correlation coefficient being 0.84.
PMID- 27485693
TI - Downregulation of AATK mediates microRNA-558-induced resistance of A549 cells to
radiotherapy.
AB - The deregulation of microRNAs (miRNAs) is often implicated in the control of
sensitivity to radiotherapy. The objective of the present study was to identify
the association between miR-558 and apoptosis-associated tyrosine kinase (AATK),
and their importance in regulating the development of resistance to radiotherapy.
The current study demonstrated that AATK, a radiosensitization-associated gene,
is a target of miR-558 in lung cancer cells, using in silico analysis and a
luciferase reporter system. Furthermore, it was determined that transfection of
30 or 50 nM miR-558 mimics and AATK specific siRNA markedly suppressed the mRNA
and protein expression of AATK. To determine whether miR-558 was required for
lung cancer cell radioresistance, A549 cells were treated with different doses of
ionizing radiation, from 0 to 10 Gy, following transfection with miR-558 mimics
or AATK specific siRNA. It was determined that the administration of miR-558
mimics or AATK specific siRNA alone did not significantly alter the survival rate
of the cells. By contrast, in the cells exposed to 4, 6 or 8 Gy, the
administration of miR-558 mimics or AATK specific siRNA significantly promoted
cell survival rate and overexpression of AATK reversed this effect. In
conclusion, these data demonstrate that the miR-558/AATK cascade is important for
the radiosensitization of lung cancer cells and may be a potential radiotherapy
target.
PMID- 27485694
TI - Relationships between milks differentiated on native milk fat globule
characteristics and fat, protein and calcium compositions.
AB - Many studies have shown that milk fat globule (MFG) diameter varies in dairy cows
in relation to diet and/or breed. However, the mechanisms governing the size of
the fat globules remain hypothetical. Our objective was to determine the variable
biochemical characteristics (fat, protein, fatty acids (FA), casein and calcium
(Ca) contents) between individual milk which differed in both MFG diameter and
membrane content, in order to speculate about the links between milk synthesis
and MFG secretion. With this aim, we built five databases of individual milk
samples from 21 experiments performed between 2003 and 2011. Three of them
grouped data from trials dealing with breed/diet effects and included information
about: (i) MFG size/membrane, fat and protein contents (n=982), (ii) previous
parameters plus FA profile (n=529) and (iii) previous parameters plus true
protein composition and calcium contents (n=101). A hierarchical clustering
analysis performed on these three databases yielded four groups differing in the
MFG characteristics. We observed significant differences among groups for the
following parameters: (i) fat content and fat : protein ratio; (ii) de novo and
polyunsaturated FA contents; (iii) Ca contents. These relationships could result
from potential process regulating the synthesis and secretion of MFG: (i) the
apical membrane turnover for MFG secretion and (ii) cytoplasmic lipid droplet
formation in the lactocyte during its migration from the basal to the apical
pole. The two other databases grouped data from trials dealing with milking
frequency (n=211), milking kinetics and milk type (residual v. cisternal)
(n=224). They were used to study the relationships between the size of the MFG
and milk composition for high native fat contents (from 60 up to 100 g/kg in
residual milks). We observed curvilinear relationships between the size of the
MFG and fat content, as well as with the fat : protein ratio. This result
suggests that MFG diameter reaches a threshold but mechanisms are still unknown.
PMID- 27485695
TI - Spinal Cord Infarction in Hemoglobin SC Disease as an Amusement Park Accident.
AB - Spinal cord infarction (SCI) is extremely rare in children, and only 2 other
reports have described the occurrence of SCI in patients with hemoglobin SC
disease (HbSC). Amusement park accidents are serious injuries. Patients with
preexisting conditions, such as hypertension, cardiac disease, and recent back or
neck injuries, may be at an increased risk. We report the case of a 12-year-old
girl with HbSC with a past history of only 2 admissions for pain crises, who
presented to the emergency department with symptoms of SCI after riding a roller
coaster. Fibrocartilaginous embolism (FCE) is an increasingly recognized cause of
SCI after events that put strain on the axial skeleton, such as many amusement
park rides. Although radiologic criteria for FCE have been proposed, FCE remains
a diagnosis of exclusion. To the best of our knowledge, this is the first
documented case of SCI in a patient with HbSC and the first case of FCE after an
amusement park accident. This case report highlights that HbSC may confound the
differential diagnosis of SCI and aims to document an association with FCE in
pediatric patients.
PMID- 27485697
TI - 30th Anniversary of Pediatric Research in Office Settings (PROS): An Invitation
to Become Engaged.
PMID- 27485698
TI - Observations of disorganized behaviour yield no magic wand: response to
Shemmings.
PMID- 27485696
TI - Parent Experience With False-Positive Newborn Screening Results for Cystic
Fibrosis.
AB - BACKGROUND: The risk of psychosocial harm in families of infants with false
positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF)
is a longstanding concern. Whether well designed retrieval and confirmatory
testing systems can mitigate risks remains unknown. METHODS: Using a mixed
methods cohort design, we obtained prospective self-report data from mothers of
infants with FP CF NBS results 2 to 3 months after confirmatory testing at
Ontario's largest follow-up center, and from a randomly selected control sample
of mothers of screen negative infants from the same region. Mothers completed a
questionnaire assessing experience and psychosocial response. A sample of mothers
of FP infants completed qualitative interviews. RESULTS: One hundred thirty-four
mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%)
completed questionnaires; 54 mothers of FP infants were interviewed. Selected
psychosocial response measures did not detect psychosocial distress in newborns
or 1 year later (P > .05). Mothers recalled distress during notification of the
positive result and in the follow-up testing period related to fear of chronic
illness, but valued the screening system of care in mitigating concerns.
CONCLUSIONS: Although immediate distress was reported among mothers of FP
infants, selected psychometric tools did not detect these concerns. The NBS
center from which mothers were recruited minimizes delay between notification and
confirmatory testing and ensures trained professionals are communicating results
and facilitating follow-up. These factors may explain the presence of minimal
psychosocial burden. The screening system reflected herein may be a model for NBS
programs working to minimize FP-related psychosocial harm.
PMID- 27485699
TI - Labilizing the Photoinert: Extraordinarily Facile Photochemical Ligand Ejection
in an [Os(N^N)3 ](2+) Complex.
AB - Whilst [Os(N^N)3 ](2+) complexes are supposed to be photochemically inert to
ligand loss, the complex [Os(btz)3 ](2+) (btz=1,1'-dibenzyl-4,4'-bi-1,2,3
triazolyl) undergoes unprecedented photolytic reactivity to liberate free btz
(Phi363 ~1.2 %). Further, both cis and trans isomers of the photodechelated
ligand-loss solvento intermediate [Os(kappa(2) -btz)2 (kappa(1) -btz)(NCMe)](2+)
are unambiguously observed and characterized by NMR spectroscopy and mass
spectrometry.
PMID- 27485700
TI - The Importance of Innate Immunity in Acne.
PMID- 27485701
TI - Interference in transcription of overexpressed genes by promoter-proximal
downstream sequences.
AB - Despite a high sequence homology among four human RNAi-effectors Argonaute
proteins and their coding sequences, the efficiency of ectopic overexpression of
AGO3 and AGO4 coding sequences in human cells is greatly reduced as compared to
AGO1 and AGO2. While investigating this phenomenon, we documented the existence
of previously uncharacterized mechanism of gene expression regulation, which is
manifested in greatly varying basal transcription levels from the RNApolII
promoters depending on the promoter-proximal downstream sequences. Specifically,
we show that distinct overexpression of Argonaute coding sequences cannot be
explained by mRNA degradation in the cytoplasm or nucleus, and exhibits on
transcriptional level. Furthermore, the first 1000-2000 nt located immediately
downstream the promoter had the most critical influence on ectopic gene
overexpression. The transcription inhibiting effect, associated with those
downstream sequences, subsided with increasing distance to the promoter and
positively correlated with promoter strength. We hypothesize that the same
mechanism, which we named promoter proximal inhibition (PPI), could generally
contribute to basal transcription levels of genes, and could be mainly
responsible for the essence of difficult-to-express recombinant proteins.
Finally, our data reveal that expression of recombinant proteins in human cells
can be greatly enhanced by using more permissive promoter adjacent downstream
sequences.
PMID- 27485702
TI - The Association between Diabetes and Herpes Simplex Eye Disease.
AB - PURPOSE: To evaluate the association between diabetes mellitus (DM) and presence
and severity of Herpes simplex eye disease (HSED). METHODS: We conducted two sub
studies. We included the patients seen on the Cornea Service of the Wills Eye
Hospital from January 2008 to August 2012. Study 1 included 541 patients with
HSED and 3226 controls. Study 2 involved 40 diabetic and 120 non-diabetic ocular
surface HSED patients. Severity of ocular surface HSED was graded as mild,
moderate, or severe, based on best-corrected visual acuity (BCVA). Patients were
excluded if they had fewer than two office visits or had non-Herpes simplex
related vision-threatening conditions. Diabetes was graded as: diet group (DM
controlled with diet), oral group (DM controlled with oral medications), and
insulin group (DM control required insulin). RESULTS: Five of 541 (0.93%) HSED
patients had type 1 DM, similar to 19/3246 (0.59%) controls (p = 0.375); 48 of
541 (8.88%) HSED patients had type 2 DM, similar to 287/3246 (8.84%) controls (p
= 0.981). Using multinomial logistic regression analyses, the probability/risk of
being in the severe ocular surface HSED group as opposed to the mild ocular
surface HSED group were not statistically significantly different between DM
patients and those without DM (p = 0.120; OR, 1.900; 95% CI, 0.846-4.266).
CONCLUSIONS: There may not be a positive association between type 2 DM and HSED.
PMID- 27485703
TI - Postpartum unconscious dynamics emerging from the Luscher color test in Ethiopian
women.
AB - The aim of this study was to explore the feasibility of the Luscher color test
(LCT), a psychological instrument based on theory that colors are selected in
unconscious way and that the color sensory perception of color is objective and
universal. The research has involved 24 Ethiopian women, which delivered at the
Getche Health Center in Gurage. It seemed to be relevant for the majority of
Ethiopian women identify the rejected color (58.66%), the gray, than the favorite
color, the yellow 33.33%). The yellow color suggests that they better express
their personality in a physical context, while the gray color indicates that they
want to live this experience intensely. This exploratory work lays the
foundations for further studies in disadvantaged women, both in developing low
income Countries as well as in industrialized Countries characterized by an high
level of emigration, and for clinical applications by the complete LCT version.
PMID- 27485704
TI - Intrapartum transvaginal sonographic imaging of mentum posterior presentation at
39 weeks' gestation.
PMID- 27485705
TI - Strabismus and Near Point of Convergence and Amblyopia in 4-6 Year-Old Children.
AB - PURPOSE: To determine the prevalence of strabismus and amblyopia, and the
distribution of the near point of convergence (NPC), in a population of children
aged 4 to 6 years. METHODS: In this cross-sectional study, preschoolers in
Mashhad were sampled using a random multistage cluster sampling approach.
Examinations were done after obtaining parental consent. All participants had
measurements of uncorrected visual acuity, corrected visual acuity, and non
cycloplegic refraction, and they had near and far cover tests to determine tropia
and phoria. RESULTS: Of the 3765 selected children, 3701 participated in the
study. The prevalence of tropia was 1.21% (95% confidence interval [CI]: 0.86
1.57). Near and near/far tropia was observed in 0.83% (95% CI: 0.53-1.12) and
0.39% (95% CI: 0.18-0.59), respectively. Tropia was significantly more prevalent
in boys (P=0.005). The most common type of tropia was esotropia, 0.22% (95% CI:
0.07-0.37). Among participants, 63.92% (95% CI: 62.36-65.48) had phoria;
prevalence of far, near, and near/far phoria was 0.22% (95% CI: 0.07-0.37),
60.47% (95% CI: 58.88-62.07), and 3.22% (95% CI: 2.65-3.8), respectively. Mean
NPC was 5.1 cm (95% CI: 5.05-5.14). NPC increased by 0.08 cm per month of age
(P=0.033) and was 0.10 cm higher in boys compared to girls (P=0.027). Based on
NPC, 61.58% (95% CI: 59.99-63.17) were symptomatic. The prevalence of amblyopia
was 0.41% (95% CI: 0.20-0.61). The type of amblyopia was anisometropic,
strabismic, and isoametropic in 75%, 11.1%, and 8.5%, respectively. CONCLUSION:
The prevalence of amblyopia in this study population was not high; however, the
prevalence of tropia was average compared to previous studies in Iran. Describing
NPC in a 4- to 6-year-old Iranian population for the first time, we found that
NPC increased with age in this sample.
PMID- 27485706
TI - Elevated DRD4 promoter methylation increases the risk of Alzheimer's disease in
males.
AB - Aberrant promoter methylation of multiple genes is associated with various
diseases, including Alzheimer's disease (AD). The goal of the present study was
to determine whether dopamine receptor D4 (DRD4) promoter methylation is
associated with AD. In the current study, the methylation levels of the DRD4
promoter were measured in 46 AD patients and 61 controls using bisulfite
pyrosequencing technology. The results of the present study demonstrated that
DRD4 promoter methylation was significantly higher in AD patients than in
controls. A further breakdown analysis by gender revealed that there was a
significant association of DRD4 promoter methylation with AD in males (23
patients and 45 controls). In conclusion, the results of the present study
demonstrated that elevated DRD4 promoter methylation was associated with AD risk
in males.
PMID- 27485707
TI - The role of IGF-1 and the distribution of body fat in decreasing the number of
prostate rebiopsies.
AB - OBJECTIVE: To assess the usefulness of IGF-1 and internal organ fat measured by
bioelectrical impedance audiometry to avoid rebiopsies in patients with
persistently high prostate-specific antigen (PSA) levels. MATERIAL AND METHOD: A
prospective study was conducted with 92 patients who underwent prostate rebiopsy
due to high PSA levels with negative results in the rectal examination and a lack
of preneoplastic lesions. The patients previously had their IGF-1 levels measured
and had undergone an impedance audiometry test using the abdominal Fat Analyser
AB-140 TANITA system. We calculated the receiver operating characteristic (ROC)
curves for the PSA levels, %PSA, internal organ fat and IGF-1 and PSA density.
RESULTS: Twenty-five patients were diagnosed with prostate cancer. These patients
had significantly higher PSA, PSAd and IGF-1 values and a tendency towards higher
internal organ fat levels and lower %PSA readings (p=.001, p=.003, p=.001, p=.24
and P=0.28, respectively). The ROC curve showed an area under the curve for IGF-1
and PSA of .82 and .81, respectively. Using the cutoff points for 95% sensitivity
and using the 3 criteria as an indication of rebiopsy, 74% of the biopsies would
have been spared, leaving undiagnosed only 1 patient with clinically significant
cancer -Gleason score>7 (4+3)-. The positive and negative predictive values for
the set of variables were higher than for each one separately (PPV: 66/NPV: 63).
The cost of both determinations was 82 euros. CONCLUSIONS: Our results suggest
that measuring IGF-1 could significantly decrease the number of unnecessary
rebiopsies in an inexpensive and safe manner.
PMID- 27485708
TI - A review of current methods using bacteriophages in live animals, food and animal
products intended for human consumption.
AB - Bacteriophages are utilised in the food industry as biocontrol agents to reduce
the load of bacteria, and thus reduce potential for human infection. This review
focuses on current methods using bacteriophages within the food chain.
Limitations of research will be discussed, and the potential for future food
based bacteriophage research.
PMID- 27485709
TI - Evaluation of real-time PCR assays and standard curve optimisation for enhanced
accuracy in quantification of Campylobacter environmental water isolates.
AB - Campylobacter is a major public health and economic burden in developed and
developing countries. This study evaluated published real-time PCR (qPCR) assays
for detection of Campylobacter to enable selection of the best assays for
quantification of C. spp. and C. jejuni in environmental water samples. A total
of 9 assays were compared: three for thermotolerant C. spp. targeting the 16S
rRNA and six for C. jejuni targeting different genes. These assays were tested in
the wet-lab for specificity and sensitivity against a collection of 60,
genetically diverse, Campylobacter isolates from environmental water. All three
qPCR assays targeting C. spp. were positive when tested against the 60 isolates,
whereas, assays targeting C. jejuni differed among each other in terms of
specificity and sensitivity. Three C. jejuni-specific assays that demonstrated
good specificity and sensitivity when tested in the wet-lab showed concordant
results with in silico-predicted results obtained against a set of 211 C. jejuni
and C. coli genome sequences. Two of the assays targeting C. spp. and C. jejuni
were selected to compare DNA concentration estimation, using spectrophotometry
and digital PCR (dPCR), in order to calibrate standard curves (SC) for greater
accuracy of qPCR-based quantification. Average differences of 0.56+/-0.12 and
0.51+/-0.11 log fold copies were observed between the spectrophotometry-based SC
preparation and the dPCR preparation for C. spp. and C. jejuni, respectively,
demonstrating an over-estimation of Campylobacter concentration when
spectrophotometry was used to calibrate the DNA SCs. Our work showed differences
in quantification of aquatic environmental isolates of Campylobacter between qPCR
assays and method-specific bias in SC preparation. This study provided an
objective analysis of qPCR assays targeting Campylobacter in the literature and
provides a framework for evaluating novel assays.
PMID- 27485710
TI - Kostmann syndrome: oral aspects and 10-year follow-up case report.
AB - Kostmann syndrome (KS) is an autosomal recessive disorder characterized by a low
neutrophil count and recurrent bacterial infections, including periodontal
disease. This report describes the case of a 5-year-old female KS patient treated
with regular infusions of granulocyte stimulating factor (granulokine), with
primary complaint of gingival bleeding and tooth mobility, and followed up for 10
years. Conventional periodontal treatment and some extractions were performed,
after neutrophil function tests using flow cytometry. The invasive procedures
were carried out at an outpatient clinic under antibiotic prophylaxis due to a
low neutrophil count and an impaired neutrophil function presented. During the 10
year follow-up period, despite episodes of recurrent gingivitis and periodontitis
the present report describes the positive outcome of dental treatment of a
patient with KS.
PMID- 27485711
TI - [Algorithm for Choosing the Study Design in Systematic Reviews].
AB - Background: The Federal Joint Committee (Gemeinsamer Bundesausschuss) assigns the
highest evidence level of Ia to systematic reviews of randomized controlled
trials in evaluating the benefit of therapeutic interventions. Contradictory
results among randomized and non-randomized studies may not always be caused by
the study design. Methods: The objective of the study was to identify statements
in systematic or non-systematic reviews about the choice of study designs in
systematic reviews. Another objective was to develop an algorithm to facilitate
the choice of appropriate study designs in systematic reviews. Results: The
inclusion of non-randomized in addition to randomized study designs was supported
by 85% of the 42 identified articles. A strong reason was the need to evaluate
the possible treatment-associated harm. The developed algorithm included the 4
decision points of length of follow-up, frequency of events, outcomes, and study
designs. Conclusions: If the benefit and the harm of a therapeutic intervention
is planned to be evaluated, then often multiple study designs are required to be
included. The algorithm provides guidance on which study designs should be
considered for inclusion in systematic reviews.
PMID- 27485712
TI - The Red Nucleus Interleukin-6 Participates in the Maintenance of Neuropathic Pain
Induced by Spared Nerve Injury.
AB - Previous studies have demonstrated that the red nucleus (RN) is involved in the
regulation of neuropathic pain and plays both facilitated and inhibitory roles
through different cytokines. Here, we aim to investigate the expression changes
and roles of interleukin-6 (IL-6), a pleiotropic cytokine, as well as its
receptor (IL-6R) in the RN of rats with neuropathic pain induced by spared nerve
injury (SNI). Immunohistochemistry indicated that IL-6 and IL-6R were weakly
expressed in the RN of normal rats, and were mainly co-localized with neurons and
oligodendrocytes. Following SNI, the expression levels of IL-6 and IL-6R in the
RN did not show obvious changes at 1 week and 2 weeks postinjury. However, both
of them were significantly increased in the RN contralateral (but not
ipsilateral) to the nerve ligation side at 3 weeks postinjury, and co-localized
not only with neurons and oligodendrocytes, but also with numerous astrocytes.
Injection of different doses of anti-IL-6 antibody (100, 250, 500 ng) into the RN
contralateral to the nerve ligation side at 3 weeks postinjury dose-dependently
increased the paw withdrawal threshold (PWT) of rats and alleviated SNI-induced
mechanical allodynia. Conversely, injection of different doses of recombinant rat
IL-6 (5.0, 10, 20 ng) into the unilateral RN of normal rats dose-dependently
decreased the PWT of contralateral (but not ipsilateral) hind paw and evoked
significant mechanical allodynia, which was similar to SNI-induced neuropathic
allodynia. These results further support the conclusion that the RN is involved
in the modulation of neuropathic pain, and suggest that IL-6 and IL-6R in the RN
play a facilitated role in the later maintenance of SNI-induced neuropathic pain.
PMID- 27485713
TI - Uptake and Toxicity of Copper Oxide Nanoparticles in C6 Glioma Cells.
AB - Copper oxide nanoparticles (CuO-NPs) are frequently used for many technical
applications, but are also known for their cell toxic potential. In order to
investigate a potential use of CuO-NPs as a therapeutic drug for glioma
treatment, we have investigated the consequences of an application of CuO-NPs on
the cellular copper content and cell viability of C6 glioma cells. CuO-NPs were
synthesized by a wet-chemical method and were coated with dimercaptosuccinic acid
and bovine serum albumin to improve colloidal stability in physiological media.
Application of these protein-coated nanoparticles (pCuO-NPs) to C6 cells caused a
strong time-, concentration- and temperature-dependent copper accumulation and
severe cell death. The observed loss in cellular MTT-reduction capacity, the loss
in cellular LDH activity and the increase in the number of propidium iodide
positive cells correlated well with the specific cellular copper content. C6
glioma cells were less vulnerable to pCuO-NPs compared to primary astrocytes and
toxicity of pCuO-NPs to C6 cells was only observed for incubation conditions that
increased specific cellular copper contents above 20 nmol copper per mg protein.
Both cellular copper accumulation as well as the pCuO-NP-induced toxicity in C6
cells were prevented by application of copper chelators, but not by endocytosis
inhibitors, suggesting that liberation of copper ions from the pCuO-NPs is the
first step leading to the observed toxicity of pCuO-NP-treated glioma cells.
PMID- 27485714
TI - Protective Effect of Hyperbaric Oxygen on Cognitive Impairment Induced by D
Galactose in Mice.
AB - Memory decline is characteristic of aging and age-related neurodegenerative
disorders. This study was designed to investigate the protective effect of
hyperbaric oxygen (HBO) against cognitive impairment induced by D-galactose (D
gal) in mice. D-gal was intraperitoneally injected into mice daily for 8 weeks to
establish the aging model. HBO was simultaneously administered once daily. The
results indicate that HBO significantly reversed D-gal-induced learning and
memory impairments. Studies on the potential mechanisms of this action showed
that HBO significantly reduced oxidative stress by increasing superoxide
dismutase, glutathione peroxidase, and catalase levels, as well as the total anti
oxidation capability, while decreasing the content of malondialdehyde, nitric
oxide, and nitric oxide synthase in the hippocampal CA1 region. HBO also
inhibited advanced glycation end-product formation and decreased levels of tumor
necrosis factor-alpha and interleukin-6. Moreover, HBO significantly attenuated D
gal-induced pathological injury in the hippocampus, as well as beta-amyloid
protein1-42 expression and retained BDNF expression. Furthermore, HBO decreased
p16, p21 and p53 gene and protein expression in the hippocampus of D-gal-treated
mice. In conclusion, the protective effect of HBO against D-gal-induced cognitive
impairment was mainly due to its ability to reduce oxidative damage, suppress
inflammatory responses, and regulate aging-related gene expression.
PMID- 27485715
TI - Colonic polyp histopathology and location in a community-based sample of older
adults.
AB - BACKGROUND: Colorectal cancer and its precursors are highly prevalent in
developed countries. Estimates in the available literature for prevalence of
right-sided-only lesions vary between 20.5 and 48.1 %, with association with
female gender and advancing age. Since the original polyp studies, premalignant
potential of sessile serrated adenomas has been described and screening
utilization of colonoscopy in men, women, and older adults has increased. This
study describes the histopathology and distribution of colorectal polyps by age
and gender in the post-screening era. METHODS: A registry of biopsies performed
during colonoscopy for adults aged 50+ years in 2002-2012 was created using
pathology reports from an independent, regional laboratory. Age, histopathology,
and polyp location(s) were included. A subgroup analysis was performed for
sessile serrated adenomas for 2007-2012. Distributions of histopathology and
polyp location were described by age and gender. Statistical comparisons are made
using chi-square tests. RESULTS: 13,881 patients (55.5 % male, 44.5 % female),
aged 50-95 years (median = 62) were identified. Most patients (59.9 %) had
adenomas. Single and multiple adenomas were more common in men than women (57.7 %
vs 42.3 %, p < .0001 and 62.2 % vs 37.8 %, p < .001), and with advancing age
(60.4 % for ages 50- < 60, 63.4 % for ages 60- < 70, 65 % for ages 70- < 80, and
68.9 % for ages >80). Villous adenomas (n = 545; 3.6 %), dysplasia (n = 49; 0.4
%), and invasive carcinoma (n = 22; 0.2 %) were rare. Sessile serrated adenomas
were uncommon (n = 417, 4.5 %), with greater prevalence in women than men (5.1 %
vs 4 %, p = 0.02). Patients aged 70- < 80 were more likely to have multiple
polyps than those aged 50- < 60 (OR 1.17, 95 % CI 1.03-1.32, p = 0.018 and OR
1.27, 95 % CI 1.10-1.46, p = .001). Most polyps were from ascending and/or
transverse colon (n = 8095; 58.3 %). When location was stratified by sex only,
men had more polyps than women at each location except the sigmoid and rectum.
Further stratification by age of location and sex revealed statistically
significant differences (age 50- < 60, p < .0001, age 60- < 70, p = .0227, age 70
< 80, p = .0298, age 80+, p = .0018). CONCLUSIONS: This large community-based
sample contributes to understanding of colonic neoplasia. The high prevalence of
right and transverse lesions supports ongoing use of colonoscopy over
sigmoidoscopy for screening examinations.
PMID- 27485716
TI - Erratum to: CoMEt: a statistical approach to identify combinations of mutually
exclusive alterations in cancer.
PMID- 27485717
TI - Facebook use and its effects on the life of health science students in a private
medical college of Nepal.
AB - BACKGROUND: Facebook, a popular social networking site, has been used by people
of different ages and professions for various purposes. Its use in the field of
medical education is increasing dramatically. At the same time, the pros and cons
of facebook use among the health science students has attracted the attention of
educators. The data regarding its use and the effect on the life of Nepalese
health science students has not yet been documented. Therefore, this study is
carried out to evaluate the effect of facebook use on social interactions,
behaviour, academics, and the health of students in a medical college of Nepal.
RESULTS: A cross-sectional descriptive study conducted among medical, dental,
nursing and allied health science students using self-administered questionnaire.
The study showed that 98.2 % of participants were facebook users. Among 452
respondents, 224 and 228 were male and female respectively, with a mean age of
20.2 +/- 1.2 years. The main reason for using facebook was to remain in contact
with family and friend (32 %), while its use for the academic purpose was only 5
%. However, 80.8 % of students acknowledged ease in acquiring academic materials
from others, through facebook. One-fourth of the students acknowledged that they
are using facebook late at night on a regular basis, while surprisingly 4.2 % of
the students admitted accessing facebook during the classroom lectures. Almost
two-third of the users, further admitted that facebook has had a negative impact
on their studies. Burning eyes (21 %), disturbed sleep (19 %), and headache (16
%) were the most common adverse health effects reported by the facebook users.
Many students (71.4 %) tried and most of them (68.7 %) succeeded, in reducing
time spent on facebook, to allow for increased time devoted to their studies.
CONCLUSION: The widespread use of facebook among the health science students, was
found to have both positive and negative effects on their academics, social life,
and health.
PMID- 27485718
TI - Parameters and outcomes in 525 patients operated on for oral squamous cell
carcinoma.
AB - PURPOSE: This report analyzed the outcomes of patients undergoing surgery for
oral squamous cell carcinoma (OSCC) to identify the value of prognostic factors.
MATERIAL AND METHODS: A total of 525 patients were studied who had undergone
surgery for oral squamous cell carcinoma (OSCC) between 2000 and 2011, of whom
222 had received postoperative radiation-therapy (PORT) and or chemoradiation
therapy (PORTC). For each patient, personal data, histological findings,
treatment and outcome were recorded and analyzed statistically. Survival curves
were calculated using the Kaplan-Meier algorithm, and the difference in survival
among subgroups was examined. RESULTS: The overall survival (OS) and disease
specific survival (DSS) 5-year survival rate in the 525 patients were
respectively 71.38% and 73.18%. The differences in the overall survival and
disease-specific 5-year survival were significant (p < 0.05) for age < 40 years,
site of origin, N status, staging, grading, osseous medullar infiltration, and
perineural invasion. In patients undergoing radiation therapy, only perineural
invasion negatively influenced the survival prognosis. In 150 pT1 cases of tongue
and floor-of-mouth cancer, an infiltration depth (ID) > 4 mm was statistically
correlated with poorer prognosis. CONCLUSIONS: The results demonstrate an
improvement in the 5-year OS and DSS rates during the past decade compared with
the previous decade. Univariate analysis revealed that age, tumor staging, and
lymph node involvement, extracapsular spread, grading, perineurial invasion,
infiltration depth, and osseus medullary invasion were associated significantly
with overall survival and disease-specific survival.
PMID- 27485719
TI - Task shifting from physicians to nurses in primary care in 39 countries: a cross
country comparative study.
AB - BACKGROUND: Primary care is in short supply in many countries. Task shifting from
physicians to nurses is one strategy to improve access, but international
research is scarce. We analysed the extent of task shifting in primary care and
policy reforms in 39 countries. METHODS: Cross-country comparative research,
based on an international expert survey, plus literature scoping review. A total
of 93 country experts participated, covering Europe, USA, Canada, Australia and
New Zealand (response rate: 85.3%). Experts were selected according to pre
defined criteria. Survey responses were triangulated with the literature and
analysed using policy, thematic and descriptive methods to assess developments in
country-specific contexts. RESULTS: Task shifting, where nurses take up advanced
roles from physicians, was implemented in two-thirds of countries (N = 27, 69%),
yet its extent varied. Three clusters emerged: 11 countries with extensive
(Australia, Canada, England, Northern Ireland, Scotland, Wales, Finland, Ireland,
Netherlands, New Zealand and USA), 16 countries with limited and 12 countries
with no task shifting. The high number of policy, regulatory and educational
reforms, such as on nurse prescribing, demonstrate an evolving trend
internationally toward expanding nurses' scope-of-practice in primary care.
CONCLUSIONS: Many countries have implemented task-shifting reforms to maximise
workforce capacity. Reforms have focused on removing regulatory and to a lower
extent, financial barriers, yet were often lengthy and controversial. Countries
early on in the process are primarily reforming their education. From an
international and particularly European Union perspective, developing
standardised definitions, minimum educational and practice requirements would
facilitate recognition procedures in increasingly connected labour markets.
PMID- 27485721
TI - En face choroidal vascular feature imaging in acute and chronic central serous
chorioretinopathy using swept source optical coherence tomography.
AB - AIMS: To evaluate the variable depth tomographic features of choroidal
vasculature in acute and chronic central serous chorioretinopathy (CSC) using
swept source optical coherence tomography (SS-OCT) en face imaging. METHODS: We
retrospectively reviewed the en face SS-OCT images of 29 patients that presented
with acute (12 eyes) or chronic (17 eyes) CSC. All of the patient eyes underwent
6*6 macular scans with SS-OCT (DRI OCT-1, Topcon, Tokyo, Japan), fluorescein
angiography and indocyanine green angiography. The en face image was used to
investigate the choroidal vasculature of each layer. Moreover, we determined that
some parts corresponded to choriocapillaris and Sattler's layer attenuation,
whereas choroidal vessel dilatation was associated with Haller's layer. RESULTS:
At Haller's layer level, choroidal vessel dilatation was observed in 11 of 12
acute CSC (91.7%) and 15 of 17 chronic CSC (88.2%). In acute CSC, choroidal
vessel dilatation was divided into focal (9/11; 81.8%) and diffuse (2/11; 18.2%)
patterns. The chronic CSC cases demonstrated different patterns of choroidal
vessel dilatation: focal (5/15; 33.3%) and diffuse (10/15; 66.6%). Ten of the
acute CSC eyes (83.3%) and 14 of the chronic CSC eyes (82.4%) were found to have
obscured choriocapillaris and Sattler's layers on en face imaging. CONCLUSIONS:
En face imaging of SS-OCT is useful when combined with angiography in CSC for
evaluating choroidal vessel dilatation at Haller's layer and to identify obscured
upper layers. We identified different choroidal vessel dilatation patterns
between acute and chronic CSC. These findings might be useful for
pathophysiological understanding of CSC.
PMID- 27485720
TI - Factors for successful implementation of population-based expanded carrier
screening: learning from existing initiatives.
AB - Background: Carrier screening for autosomal recessive disorders aims to
facilitate reproductive decision-making by identifying couples with a 1-in-4 risk
in every pregnancy of having an affected child. Except for a few countries or
regions, carrier screening is not widely offered and is mostly ancestry-based.
Technological advances enable carrier screening for multiple diseases
simultaneously allowing universal screening regardless of ancestry (population
based expanded carrier screening). It is important to study how this can be
successfully implemented. This study therefore aims to identify critical factors
involved in successful implementation, from a user perspective, by learning from
already implemented initiatives. Methods: Factors associated with successful
implementation were identified by: (i) a literature review and (ii) two case
studies; studying experiences with carrier screening in two high-risk communities
(a Dutch founder population and the Ashkenazi Jewish population), including a
survey among community members. Results: Factors identified were familiarity with
(specific) genetic diseases and its availability, high perceived benefits of
screening (e.g. screening avoids much suffering), acceptance of reproductive
options, perceived risk of being a carrier and low perceived social barriers
(e.g. stigmatization). In contrast to the Jewish community, the initial demand
for screening in the Dutch founder population did not entirely come from the
community itself. However, the large social cohesion of the community facilitated
the implementation process. Conclusion: To ensure successful implementation of
population-based expanded carrier screening, efforts should be made to increase
knowledge about genetic diseases, create awareness and address personal benefits
of screening in a non-directive way.
PMID- 27485722
TI - The impact of typical neovascular age-related macular degeneration and polypoidal
choroidal vasculopathy on vision-related quality of life in Asian patients.
AB - AIMS: To determine the impact of neovascular age-related macular degeneration
(nAMD) on vision-related quality of life (VRQoL) in an Asian population. METHODS:
In this cross-sectional study, 162 subjects with nAMD from the Asian AMD
Phenotyping Study and 105 randomly sampled age-matched and gender-matched
controls from the population-based Singapore Chinese Eye Study were recruited.
nAMD was categorised as either polypoidal choroidal vasculopathy (PCV) or
'typical' AMD (tAMD). The reading, mobility and emotional well-being subscales of
the impact of vision impairment (IVI) scale were validated using Rasch analysis
and used as the main outcome measures and collectively referred to as VRQoL.
Multivariate linear regression analyses were performed to assess the impact of
nAMD overall, and PCV and tAMD subtypes, on the three IVI domains. RESULTS: Of
the 162 with nAMD, 103 (63.6%) had PCV and 59 (36.4%) had tAMD. In multivariate
models, nAMD overall was independently associated with a 21% reduction in reading
(beta=-1.08; CI -1.58 to -0.57); 16% reduction in mobility (beta=-0.74; -1.14 to
0.33) and 44% reduction in emotional well-being (beta=-2.15; -2.83 to -1.47)
compared with controls. There were significant VRQoL deficits (p<0.05) associated
with both PCV and tAMD; these deficits were similar and not statistically
different between the two nAMD subtypes (p>0.05). CONCLUSIONS: Neovascular AMD,
including both PCV and tAMD subtypes, has a detrimental impact on VRQoL in Asian
subjects independent of level of vision impairment. Interventions to increase
reading capacity, enhance mobility and independence and improve mental health
outcomes for subjects with neovascular AMD further address the impact of the
condition on VRQoL in addition to pharmacological therapies.
PMID- 27485723
TI - Is prophylactic laser peripheral iridotomy for primary angle closure suspects a
risk factor for cataract progression? The Chennai Eye Disease Incidence Study.
AB - BACKGROUND: To report the risk of cataract progression among primary angle
closure suspects (PACS) 6 years after they underwent laser peripheral iridotomy
(LPI). METHODS: In the Chennai Eye Disease Incidence Study, 6 years after their
baseline evaluation, 4421 subjects were examined again. As part of a detailed
evaluation cataract was graded using the Lens Opacities Classification System II;
progression was defined as change of cataract by two or more grades or history of
cataract surgery in the 6-year period. Only bilaterally phakic subjects with less
than N2 or C2 or P2 cataract at baseline with no history of any form of glaucoma,
primary angle closure and pseudoexfoliation were included. RESULTS: There were
3205 eligible subjects. Of these, 190 had undergone LPI for PACS. In comparison
to the study population, they were significantly older (p<0.001), female
(p=0.008), urban residents (p=0.001) and patients with hypertension (p<0.001).
During the intervening period, 53 subjects had undergone cataract surgery. The
cataract progression rate was significantly greater (OR 1.7, 95% CI 1.3 to 2.4,
p<0.001) in those who had undergone LPI. For the study population the baseline
risk factors for progression of cataract were age (p<0.001), female gender
(p=0.01), diabetes (p<0.001) and LPI (p<0.001). Diabetes and female gender were
significant risk factors for nuclear and cortical cataract progression; LPI was a
risk factor only for cortical cataract (OR 1.6, 95% CI 1.1 to 2.3, p=0.007).
CONCLUSIONS: There was significant cataract progression in 6 years following LPI
for PACS.
PMID- 27485724
TI - Individual, social, and environmental influences on the transitions in physical
activity among emerging adults.
AB - BACKGROUND: Youth's physical activity (PA) may change across developmental
periods. Although previous studies have observed a decline in levels of PA during
adolescence, few studies have explored trends in PA during the transition from
adolescence to young adulthood and what factors may impact the transitional
change. The purpose of this study was to examine changes and predictors of change
over time in PA from 10(th) grade to post-high school. METHODS: The NEXT
Generation Health Study recruited a nationally-representative cohort of US 10(th)
graders, and administered longitudinal surveys in four waves (years) to follow up
the participants to their first year after high school. Using transition models,
the self-reported outcomes, moderate-to-vigorous PA (MVPA) and vigorous PA (VPA)
each of which was repeatedly measured by one question, were modelled in
association with wave-4 environmental-status variables and time-varying
covariates. RESULTS: There was a continuous decline in the proportion of
respondents who met or exceeded the minimum recommended level for either MVPA
(from 55.97 to 34.33 %) or VPA (from 65.96 to 54.90 %) from W1 to W4. Higher
scores of peer PA, family support and VPA planning were prospectively associated
with higher likelihood of meeting the MVPA/VPA recommendations. At wave 4,
compared to those not working, attending 4-year colleges, or living on campus,
participants working full/part time, not attending school or attending community
college level schools, and living at home or in own place were more likely to
engage in MVPA. CONCLUSIONS: Peer PA, family support, self-regulatory skills, and
environmental status after high school are critical factors that can promote
MVPA/VPA among adolescents and emerging adults.
PMID- 27485726
TI - Comparison of survival between radiation therapy and trans-oral laser
microsurgery for early glottic cancer patients; a retrospective cohort study.
AB - BACKGROUND: The literature reports various treatment methodologies, such as trans
oral laser microsurgery, radiation therapy, total/partial laryngectomies, and
concurrent radiation chemotherapy for patients with early larynx cancer. However,
at the forefront of early glottis treatment is trans-oral laser microsurgery and
radiation therapy, likely due to better functional and survival outcomes. Here we
conduct the largest Canadian head-to-head comparison of consecutive patients
treated with either radiation therapy or trans-oral laser microsurgery.
Additionally, we compare these two treatments and their 5-year survival rates
post treatment to add to the existing literature. METHODS: Charts of patients who
were diagnosed with early glottic cancer between 2006 and 2013 were reviewed.
Seventy-five patients were identified, and split into 2 groups based on their
primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan
Meier survival curves, life-tables, and the log-rank statistic were reported to
determine if there was a difference between the two treatment groups and their
disease-specific survival, disease-free survival, and total laryngectomy-free
survival. Additionally, each different survival analysis was stratified by
potential confounding variables, to help conclude which treatment is more
efficacious in this population. RESULTS: The 5-year disease-specific survival
rate is 93.3 % sigma = 0.063 and 90.8 % sigma = 0.056 for patients treated with
trans-oral laser microsurgery and radiation therapy, respectively (chi (2) <
0.001, p = 0.983). The disease free survival rate is 60.0 % (sigma =0.121) for
patients treated with trans-oral laser microsurgery, and 67.2 % (sigma = 0.074)
for those who received RT (chi (2) = 0.19, p = 0.663). Additionally, the total
laryngectomy-free survival rate is 84.1 % (sigma = 0.1) and 79.1 % (sigma =
0.072) for patients' early glottic cancer treated by trans-oral laser
microsurgery and radiation therapy, respectively (chi (2) = 0.235, p = 0.628).
Chi-square analysis of age-group versus treatment group (chi (2) = 6.455, p =
0.04) and T-stage versus treatment group (chi (2) = 11.3, p = 0.001) revealed a
statistically significant relationship, suggesting survival analysis should be
stratified by these variables. However, after stratification, there was no
statistically significant difference between the trans-oral laser microsurgery
and radiation therapy groups in any of the survival analyses. CONCLUSION: No
difference was demonstrated in the 5-year disease-specific survival, disease-free
survival, and total laryngectomy-free survival, between the RT and TLM treatment
groups. Additionally, both groups showed similar 5-year survival after
stratifying by confounding variables.
PMID- 27485725
TI - MicroRNA-mRNA regulatory networking fine-tunes the porcine muscle fiber type,
muscular mitochondrial respiratory and metabolic enzyme activities.
AB - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles
in diverse biological processes via regulation of gene expression including in
skeletal muscles. In the current study, miRNA expression profile was investigated
in longissimus muscle biopsies of malignant hyperthermia syndrome-negative Duroc
and Pietrain pigs with distinct muscle metabolic properties in order to explore
the regulatory role of miRNAs related to mitochondrial respiratory activity and
metabolic enzyme activity in skeletal muscle. RESULTS: A comparative analysis of
the miRNA expression profile between Duroc and Pietrain pigs was performed,
followed by integration with mRNA profiles based on their pairwise correlation
and computational target prediction. The identified target genes were enriched in
protein ubiquitination pathway, stem cell pluripotency and geranylgeranyl
diphosphate biosynthesis, as well as skeletal and muscular system development.
Next, we analyzed the correlation between individual miRNAs and phenotypical
traits including muscle fiber type, mitochondrial respiratory activity, metabolic
enzyme activity and adenosine phosphate concentrations, and constructed the
regulatory miRNA-mRNA networks associated with energy metabolism. It is
noteworthy that miR-25 targeting BMPR2 and IRS1, miR-363 targeting USP24, miR-28
targeting HECW2 and miR-210 targeting ATP5I, ME3, MTCH1 and CPT2 were highly
associated with slow-twitch oxidative fibers, fast-twitch oxidative fibers, ADP
and ATP concentration suggesting an essential role of the miRNA-mRNA regulatory
networking in modulating the mitochondrial energy expenditure in the porcine
muscle. In the identified miRNA-mRNA network, a tight relationship between
mitochondrial and ubiquitin proteasome system at the level of gene expression was
observed. It revealed a link between these two systems contributing to energy
metabolism of skeletal muscle under physiological conditions. CONCLUSIONS: We
assembled miRNA-mRNA regulatory networks based on divergent muscle properties
between different pig breeds and further with the correlation analysis of
expressed genes and phenotypic measurements. These complex networks relate to
muscle fiber type, metabolic enzyme activity and ATP production and may
contribute to divergent muscle phenotypes by fine-tuning the expression of genes.
Altogether, the results provide an insight into a regulatory role of miRNAs in
muscular energy metabolisms and may have an implication on meat quality and
production.
PMID- 27485727
TI - Theory-based modifications of an advanced notification letter improves screening
for bowel cancer in men: A randomised controlled trial.
AB - RATIONALE: Male participation in screening for bowel cancer is sub-optimal.
Theory-based interventions provide a means of improving screening uptake.
OBJECTIVE: To test the efficacy of modifying consumer invitation material in line
with continuum and stage theories of health behaviour on screening participation.
METHODS: N = 9216 Australian men aged 50-74 years were randomised to one of four
trial arms in a 2 * 2 factorial design randomised controlled trial. Participants
received either standard invitation material (control group), or combinations of
modified advance-notification and invitation letters. A subsample completed
baseline and endpoint behavioural surveys. RESULTS: Participants who received the
modified advance notification letter were 12% more likely to screen than those
who received the standard version (RR = 1.12, chi(2)(1) = 10.38, p = 0.001). The
modified invitation letter did not impact screening uptake (RR = 0.97, chi(2)(1)
= 0.63, p = 0.424). No significant changes in psychological variables due to the
intervention were observed. CONCLUSION: Modifications to advance notification
letters in line with health behaviour theories significantly improves screening
uptake in men. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
Registry: ACTRN12612001122842
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362688.
PMID- 27485728
TI - What health plans do people prefer? The trade-off between premium and provider
choice.
AB - Within a healthcare system with managed competition, health insurers are expected
to act as prudent buyers of care on behalf of their customers. To fulfil this
role adequately, understanding consumer preferences for health plan
characteristics is of vital importance. Little is known, however, about these
preferences and how they vary across consumers. Using a discrete choice
experiment (DCE) we quantified trade-offs between basic health plan
characteristics and analysed whether there are differences in preferences
according to age, health status and income. We selected four health plan
characteristics to be included in the DCE: (i) the level of provider choice and
associated level of reimbursement, (ii) the primary focus of provider contracting
(price, quality, social responsibility), (iii) the level of service benefits, and
(iv) the monthly premium. This selection was based on a literature study, expert
interviews and focus group discussions. The DCE consisted of 17 choice sets, each
comprising two hypothetical health plan alternatives. A representative sample (n
= 533) of the Dutch adult population, based on age, gender and educational level,
completed the online questionnaire during the annual open enrolment period for
2015. The final model with four latent classes showed that being able to choose a
care provider freely was by far the most decisive characteristic for respondents
aged over 45, those with chronic conditions, and those with a gross income over
?3000/month. Monthly premium was the most important choice determinant for young,
healthy, and lower income respondents. We conclude that it would be very unlikely
for half of the sample to opt for health plans with restricted provider choice.
However, a premium discount up to ?15/month by restricted health plans might
motivate especially younger, healthier, and less wealthy consumers to choose
these plans.
PMID- 27485729
TI - Mediating pathways between parental socio-economic position and allostatic load
in mid-life: Findings from the 1958 British birth cohort.
AB - Understanding how human environments affect our health by "getting under the
skin" and penetrating the cells, organs and physiological systems of our bodies
is a key tenet in public health research. Here, we examine the idea that early
life socioeconomic position (SEP) can be biologically embodied, potentially
leading to the production of health inequalities across population groups.
Allostatic load (AL), a composite measure of overall physiological wear-and-tear,
could allow for a better understanding of the potential biological pathways
playing a role in the construction of the social gradient in adult health. We
investigate the factors mediating the link between two components of parental
SEP, maternal education (ME) and parental occupation (PO), and AL at 44 years.
Data was used from 7573 members of the 1958 British birth cohort follow-up to age
44. AL was constructed using 14 biomarkers representing four physiological
systems. We assessed the contribution of financial/materialist,
psychological/psychosocial, educational, and health behaviors/BMI pathways over
the life course, in mediating the associations between ME, PO and AL. ME and PO
were mediated by three pathways: educational, material/financial, and health
behaviors, for both men and women. A better understanding of embodiment processes
leading to disease development may contribute to developing adapted public
policies aiming to reduce health inequalities.
PMID- 27485730
TI - Affective health bias in older adults: Considering positive and negative affect
in a general health context.
AB - RATIONALE: Because subjective health reports are a primary source of health
information in a number of medical and research-based contexts, much research has
been devoted to establishing the extent to which these self-reports of health
correspond to health information from more objective sources. One of the key
factors considered in this area is trait affect, with most studies emphasizing
the impact of negative affect (negative emotions) over positive affect (positive
emotions), and focusing on high-arousal affect (e.g., anger, excitement) over
moderate- or low-arousal affect (e.g., relaxed, depressed). OBJECTIVES: The
present study examines the impact of both Positive and Negative Affect (PA/NA)
measured by items of both high and low arousal-on the correspondence between
objective health information and subjective health reports. Another limitation of
existing literature in the area is the focus on samples suffering from a
particular diagnosis or on specific symptom reports; here, these effects are
investigated in a sample of community-dwelling older adults representing a
broader spectrum of health. METHOD: 153 older adults (Mage = 71.2) took surveys
assessing Perceived Health and Affect and underwent an objective physical health
assessment. Structural equation modeling was used to investigate the extent to
which the relationship between Objective Health and Perceived Health was
moderated by PA or NA, which would indicate the presence of affective health
bias. RESULTS: Results reveal a significant moderation effect for NA, but not for
PA; PA appeared to serve a more mediational function, indicating that NA and PA
operate on health perceptions in distinct ways. CONCLUSIONS: These findings
provide evidence that in our high-functioning, community-dwelling sample of older
adults, a) affective health bias is present within a general health context, and
not only within specific symptom or diagnostic categories; and b) that both PA
and NA play important roles in the process.
PMID- 27485731
TI - Variation of partial transferrin sequences and phylogenetic relationships among
hares (Lepus capensis, Lagomorpha) from Tunisia.
AB - North African hares are currently included in cape hares, Lepus capensis sensu
lato, a taxon that may be considered a superspecies or a complex of closely
related species. The existing molecular data, however, are not unequivocal, with
mtDNA control region sequences suggesting a separate species status and nuclear
loci (allozymes, microsatellites) revealing conspecificity of L. capensis and L.
europaeus. Here, we study sequence variation in the intron 6 (468 bp) of the
transferrin nuclear gene, of 105 hares with different coat colour from different
regions in Tunisia with respect to genetic diversity and differentiation, as well
as their phylogenetic status. Forty-six haplotypes (alleles) were revealed and
compared phylogenetically to all available TF haplotypes of various Lepus species
retrieved from GenBank. Maximum Likelihood, neighbor joining and median joining
network analyses concordantly grouped all currently obtained haplotypes together
with haplotypes belonging to six different Chinese hare species and the African
scrub hare L. saxatilis. Moreover, two Tunisian haploypes were shared with L.
capensis, L timidus, L. sinensis, L. yarkandensis, and L. hainanus from China.
These results indicated the evolutionary complexity of the genus Lepus with the
mixing of nuclear gene haplotypes resulting from introgressive hybridization
or/and shared ancestral polymorphism. We report the presence of shared ancestral
polymorphism between North African and Chinese hares. This has not been detected
earlier in the mtDNA sequences of the same individuals. Genetic diversity of the
TF sequences from the Tunisian populations was relatively high compared to other
hare populations. However, genetic differentiation and gene flow analyses (AMOVA,
FST, Nm) indicated little divergence with the absence of geographically
meaningful phylogroups and lack of clustering with coat colour types. These
results confirm the presence of a single hare species in Tunisia, but a sound
inference on its phylogenetic position would require additional nuclear markers
and numerous geographically meaningful samples from Africa and Eurasia.
PMID- 27485732
TI - Parallel study about the effects of psychotherapy on patients with dental phobia
determined by anxiety scores and saliva secretion and composition.
AB - BACKGROUND: The aim of this study was to determine the success of
psychotherapeutic treatment for dental phobia by measurement of anxiety using the
dental anxiety score (DAS), the state trait anxiety score (STAI state), salivary
cortisol and protein concentrations and the salivary secretion rate. Primary
endpoint of the study was the comparison of the data before and after
psychotherapeutic treatment. METHODS: Forty patients were included into the
study. Twenty-four were allocated to the phobic group, 16 to the control group.
Saliva was collected upon entering the dental clinic and again after three weeks
of psychotherapy. The results were compared with those of a control group. The
DAS and STAI questionnaires were completed at each visit. RESULTS: A reduction in
DAS values was found after psychotherapy. However, the values remained
significantly higher in the phobic group than in the controls. Similar results
were found for STAI scores. A slightly higher salivary cortisol level was found
in the phobic group. No changes occurred in cortisol or protein concentrations.
The salivary secretion rate increased in the phobic patients after psychotherapy.
CONCLUSIONS: It could be concluded that psychotherapy is effective in the
treatment of dental phobic patients. TRIAL REGISTRATION: This study has been
retrospectively registered in the German Clinical Trials Register (# DRKS00009552
) on 10/19/15.
PMID- 27485733
TI - "Safety and utility of percutaneous liver biopsy in hematopoietic stem cell
transplant pediatric recipients: a retrospective study".
AB - BACKGROUND: Liver biopsies in pediatric hematopoietic stem cell transplantation
(HSCT) patients are as and effective when performed at bedside in the Bone Marrow
Transplant Unit (BMTU) than in the Day Surgery Unit (DSU), with better patient
compliance and lower emotional distress for these children. METHODS: The study
group consisted of 45 children who underwent allogeneic HSCT. We reviewed 68
liver biopsies performed between April 2006 and September 2015. 12 (17.6 %)
biopsies were performed in the DSU and 56 (82.3 %) in the BMTU; nine (13.2 %)
prior to HSCT and 59 (86.7 %) after HSCT. Pre-procedural behavioral status
(subjective score) was evaluated by pediatric transplant physicians by filling in
a questionnaire employing a three-point scale: "calm and cooperative", "agitated
and non-cooperative" or "frightened and suffering". Objective score was obtained
measuring patient's heart rate before the procedure and comparing it with mean
heart rate. RESULTS: Patients who underwent the procedure at the BMTU experienced
less emotional distress than those who underwent it in the DSU: 58.3 % of
patients treated at the DSU were agitated as compared with 16.1 % of those
treated at the BMTU (p < 0.01). Among the 59 biopsies performed after HSCT, 41
(69.5 %) were taken from symptomatic patients for a diagnostic purpose and 18
(30.5 %) in asymptomatic ones in order to rule out hepatic GVHD. Among these 18
procedures, GVHD was diagnosed in 16 (88.9 %) cases. Minor complications occurred
in about 17 % of procedures (12 biopsies), at a rate of 25 % for the DSU location
compared with 16 % for the BMTU location. Only two major complications were
reported, one in the DSU and one in the BMTU. CONCLUSION: Liver biopsy performed
at bedside in HSCT patients does not carry a higher risk of adverse events than
the same procedure performed in the DSU and has lower emotional distress
associated with better patient compliance, thus contributing significantly to a
higher standard of care.
PMID- 27485734
TI - Primate superior colliculus neurons activated by unexpected sensation.
AB - Midbrain superior colliculus (SC) contains a variety of neuronal types,
influencing a rich spectrum of functions beyond gaze orienting. Here, we report
on a novel class of SC neurons in the rhesus monkey (Macaca mulatta) that are
activated by an unexpected perturbation in a goal-directed arm-movement task. One
monkey subject reached for and pressed an illuminated target on a working panel
upon a visual go-signal, while maintaining visual fixation elsewhere. On 50 % of
trials, a task perturbation occurred-the working panel abruptly and unexpectedly
moved against the subject's hand after he pressed the target. During the
performance, we recorded single SC neurons and found neurons activated
exclusively for the task perturbation. These perturbation neurons were localized
in the deep lateral zone of the SC, were silent during non-perturbed trials, did
not appear to respond to task-irrelevant stimuli, and they had intriguingly long
neuronal latencies. If the perturbation neurons' activity relates to the hand
target contact, it may reflect the saliency of an unexpected sensation, i.e. a
sensation that is not self-induced and thus cannot be predicted on a basis of the
monkey's motor program.
PMID- 27485736
TI - Erratum to: Variable-Internal-Stores models of microbial growth and metabolism
with dynamic allocation of cellular resources.
PMID- 27485735
TI - STAT5 is a key transcription factor for IL-3-mediated inhibition of RANKL-induced
osteoclastogenesis.
AB - Among the diverse cytokines involved in osteoclast differentiation, interleukin
(IL)-3 inhibits RANKL-induced osteoclastogenesis. However, the mechanism
underlying IL-3-mediated inhibition of osteoclast differentiation is not fully
understood. Here we demonstrate that the activation of signal transducers and
activators of transcription 5 (STAT5) by IL-3 inhibits RANKL-induced
osteoclastogenesis through the induction of the expression of Id genes. We found
that STAT5 overexpression inhibited RANKL-induced osteoclastogenesis. However,
RANKL did not regulate the expression or activation of STAT5 during osteoclast
differentiation. STAT5 deficiency prevented IL-3-mediated inhibition of
osteoclastogenesis, suggesting a key role of STAT5 in IL-3-mediated inhibition of
osteoclast differentiation. In addition, IL-3-induced STAT5 activation
upregulated the expression of Id1 and Id2, which are negative regulators of
osteoclastogenesis. Overexpression of ID1 or ID2 in STAT5-deficient cells
reversed osteoclast development recovered from IL-3-mediated inhibition.
Importantly, microcomputed tomography and histomorphometric analysis revealed
that STAT5 conditional knockout mice showed reduced bone mass, with an increased
number of osteoclasts. Furthermore, IL-3 inhibited RANKL-induced osteoclast
differentiation less effectively in the STAT5 conditional knockout mice than in
the wild-type mice after RANKL injection. Taken together, our findings indicate
that STAT5 contributes to the remarkable IL-3-mediated inhibition of RANKL
induced osteoclastogenesis by activating Id genes and their associated pathways.
PMID- 27485737
TI - Burden of Heart Failure in Adults with Congenital Heart Disease.
AB - Patients born with congenital heart disease (CHD) have benefited from remarkable
advances in surgical and catheter-based interventions. As a result, the majority
of children born with even the most complex forms of CHD live into adulthood. The
specialized field of adult CHD (ACHD) was born out of the necessity to care for
this new population of survivors of childhood CHD and their distinctive features.
In this review, relevant aspects of ACHD that lead to, and are affected by, heart
failure will be examined along with the increasing prevalence of HF in the
burgeoning population of ACHD. We also highlight the challenges in defining HF in
this particular group of patients.
PMID- 27485738
TI - From ZikV genome to vaccine: in silico approach for the epitope-based peptide
vaccine against Zika virus envelope glycoprotein.
AB - Zika virus (ZikV) has emerged as a potential threat to human health worldwide. A
member of the Flaviviridae, ZikV is transmitted to humans by mosquitoes. It is
related to other pathogenic vector-borne flaviviruses including dengue, West Nile
and Japanese encephalitis viruses, but produces a comparatively mild disease in
humans. As a result of its epidemic outbreak and the lack of potential
medication, there is a need for improved vaccine/drugs. Computational techniques
will provide further information about this virus. Comparative analysis of ZikV
genomes should lead to the identification of the core characteristics that define
a virus family, as well as its unique properties, while phylogenetic analysis
will show the evolutionary relationships and provide clues about the protein's
ancestry. Envelope glycoprotein of ZikV was obtained from a protein database and
the most immunogenic epitope for T cells and B cells involved in cell-mediated
immunity, whereas B cells are primarily responsible for humoral immunity. We
mainly focused on MHC class I potential peptides. YRIMLSVHG, VLIFLSTAV and
MMLELDPPF, GLDFSDLYY are the most potent peptides predicted as epitopes for CD4+
and CD8+ T cells, respectively, whereas MMLELDPPF and GLDFSDLYY had the highest
pMHC-I immunogenicity score and these are further tested for interaction against
the HLA molecules, using in silico docking techniques to verify the binding cleft
epitope. However, this is an introductory approach to design an epitope-based
peptide vaccine against ZikV; we hope that this model will be helpful in
designing and predicting novel vaccine candidates.
PMID- 27485739
TI - Level of adherence to ocular hypotensive agents and its determinant factors among
glaucoma patients in Menelik II Referral Hospital, Ethiopia.
AB - BACKGROUND: Good adherence to ocular hypotensive agents is important to control
intraocular pressure and hence to prevent progressive glaucomatous optic nerve
head damage. Periodic investigation of adherence is crucial in glaucoma
treatment. The purpose of this study was to assess level of adherence to ocular
hypotensive agents and to identify factors affecting adherence among glaucoma
patients at a tertiary public eye care center. METHODS: The study was a hospital
based cross-sectional study that was conducted in Menelik II Referral Hospital
from June 1, 2015 to July 31, 2015. A systematic random sampling technique was
used to select 359 study participants from the source population. The study
patients were interviewed and their medical charts were reviewed using a
pretested structured questionnaire. Adherence was assessed using Morisky
Medication Adherence Scale - 8 and adherence determinant factors were identified
using multivariate binary logistic regression analysis. The association was
declared statistically significant at p < 0.05. RESULTS: Among the 359 study
glaucoma patients, 42.6 % were adherent to their prescribed hypotensive agents.
Higher educational level (AOR = 4.60, 95 % CI: 1.01-21.03, p < 0.049), being self
- employed (AOR = 6.14, 95 % CI: 1.37-27.50, p < 0.018) and taking lesser
frequency of drops (AOR = 2.89, 95 % CI: 1.25-6.66, p < 0.013) were significantly
associated with adherence, whereas being a farmer (AOR = 0.07, 95 % CI: 0.01
0.75, p < 0.028), having very low monthly family income (AOR = 0.22, 95 % CI:
0.06-0.77, p < 0.019) and self - purchasing of medications (AOR = 0.30, 95 % CI:
0.10-0.93, p < 0.036) were significantly associated with non-adherence.
CONCLUSIONS: The study has identified the adherence level to the prescribed
ocular hypotensive agents to be sub-optimal and is influenced by different
factors among glaucoma patients of the public tertiary center. We recommend
glaucoma care providers to pay due attention on the importance of adherence.
PMID- 27485740
TI - Assessment of the spatial accessibility to health professionals at French census
block level.
AB - BACKGROUND: The evaluation of geographical healthcare accessibility in
residential areas provides crucial information to public policy. Traditional
methods - such as Physician Population Ratios (PPR) or shortest travel time -
offer only a one-dimensional view of accessibility. This paper developed an
improved indicator: the Index of Spatial Accessibility (ISA) to measure
geographical healthcare accessibility at the smallest available infra-urban
level, that is, the Ilot Regroupe pour des Indicateurs Statistiques. METHODS:
This study was carried out in the department of Nord, France. Healthcare
professionals are geolocalized using postal addresses available on the French
state health insurance website. ISA is derived from an Enhanced Two-Step Floating
Catchment Area (E2FCA). We have constructed a catchment for each healthcare
provider, by taking into account residential building centroids, car travel time
as calculated by Google Maps and the edge effect. Principal Component Analyses
(PCA) were used to build a composite ISA to describe the global accessibility of
different kinds of health professionals. RESULTS: We applied our method to
studying geographical healthcare accessibility for pregnant women, by selecting
three types of healthcare provider: general practitioners, gynecologists and
midwives. A total of 3587 healthcare providers are potentially able to provide
care for inhabitants of the department of Nord. On average there are 92 general
practitioners, 22 midwives and 21 gynecologists per 100,000 residents. The
composite ISA for the three types of healthcare provider is 39 per 100,000
residents. A comparative analysis between ISA and physician-population ratios
indicates that ISA represents a more even distribution whereas the physician
population ratios show an 'all-or-nothing' approach. CONCLUSION: ISA is a
multidimensional and improved measure, which combines the volume of services
relative to population size with the proximity of services relative to the
population's location, available at the smallest feasible geographical scale. It
could guide policy makers towards highlighting critical areas in need of more
healthcare providers, and these areas should be earmarked for further knowledge
based policy making.
PMID- 27485741
TI - Evaluation of the pharmacokinetics and metabolism of pembrolizumab in the
treatment of melanoma.
AB - INTRODUCTION: Advanced melanoma is a devastating disease that has propelled
research in therapeutics beyond chemotherapy and radiotherapy. Being highly
immunogenic, melanoma is a model tumor for immunotherapy and has highlighted the
therapeutic potential of the immune checkpoint inhibitors. AREAS COVERED: This
review discusses the pharmacologic properties, clinical efficacy, and safety
profile of pembrolizumab, an IgG4-kappa humanized monoclonal antibody against the
programmed cell death protein 1 (PD-1) receptor, for the treatment of
unresectable or metastatic melanoma. EXPERT OPINION: Pembrolizumab was the first
PD-1 inhibitor to be approved by the U.S. Food and Drug Administration (FDA).
Remarkably, this accelerated approval for the treatment of advanced, heavily
pretreated melanoma was based on response rates alone from a phase I trial. As
anticipated, pembrolizumab confirmed a survival advantage in phase II and III
trials and has led the way for the study of other drugs that share its mechanism
of action. Defining disease and patient characteristics associated with a
response remains amongst the most pressing priorities.
PMID- 27485742
TI - High turnover rates of aerobic anoxygenic phototrophs in European freshwater
lakes.
AB - Aerobic Anoxygenic Phototrophic (AAP) bacteria are bacteriochlorophyll (BChl) a
containing organisms which use light energy to supplement their predominantly
heterotrophic metabolism. Here, we investigated mortality and growth rates of AAP
bacteria in three different freshwater lakes in Central Europe: the mountain lake
Plesne, the oligo-mesotrophic Lake Stechlin and the forest pond Huntov. The
mortality of AAP bacteria was estimated from diel changes of BChl a fluorescence.
Net and gross growth rates were calculated from the increases in AAP cell
numbers. The gross growth rates of AAP bacteria ranged from 0.38 to 5.6 d-1 ,
with the highest values observed during summer months. Simultaneously, the
rapidly growing AAP cells have to cope with an intense grazing pressure by both
zooplankton and protists. The presented results document that during the day,
gross growth usually surpased mortality. Our results indicate that AAP bacteria
utilize light energy under natural conditions to maintain rapid growth rates,
which are balanced by a generally intense grazing pressure.
PMID- 27485743
TI - Dysregulated function of normal human epidermal keratinocytes in the absence of
filaggrin.
AB - The aim of the present study was to investigate the impact of filaggrin knockdown
on the function of normal human epidermal keratinocytes (NHEKs). Filaggrin
expression levels in NHEKs were knocked down by lentivirus (LV) encoding small
hairpin RNA (shRNA), with control cells infected with nonsense shRNA or not
infected. Cell migration and invasion were assayed using Transwell inserts, cell
adhesion and proliferation by the Cell Counting kit-8 assay, and apoptosis and
cell cycle progression by flow cytometry. shRNA efficiently suppressed expression
of filaggrin protein. The LV group had significantly decreased cell migration,
adhesion and proliferation, and increased apoptosis compared with the control
groups (P=0.027). In addition, the proportion of cells in G1 and G2 phases were
significantly increased in the LV group compared with control groups (P=0.018).
The results of the present study demonstrate that filaggrin knockdown inhibits
NHEK migration, adhesion and proliferation, promotes apoptosis and disturbs cell
cycle progression.
PMID- 27485744
TI - Chemoinformatic expedition of the chemical space of fungal products.
AB - AIM: Fungi are valuable resources for bioactive secondary metabolites. However,
the chemical space of fungal secondary metabolites has been studied only on a
limited basis. Herein, we report a comprehensive chemoinformatic analysis of a
unique set of 207 fungal metabolites isolated and characterized in a USA National
Cancer Institute funded drug discovery project. RESULTS: Comparison of the
molecular complexity of the 207 fungal metabolites with approved anticancer and
nonanticancer drugs, compounds in clinical studies, general screening compounds
and molecules Generally Recognized as Safe revealed that fungal metabolites have
high degree of complexity. Molecular fingerprints showed that fungal metabolites
are as structurally diverse as other natural products and have, in general, drug
like physicochemical properties. CONCLUSION: Fungal products represent promising
candidates to expand the medicinally relevant chemical space. This work is a
significant expansion of an analysis reported years ago for a smaller set of
compounds (less than half of the ones included in the present work) from
filamentous fungi using different structural properties.
PMID- 27485745
TI - Effects of chronic sleep deprivation on bone mass and bone metabolism in rats.
AB - BACKGROUND: This study aimed to assess the effects of chronic sleep deprivation
(CSD) on bone mass and bone metabolism in rats. METHODS: Twenty-four rats were
randomly divided into CSD and control (CON) groups. Rats were subjected to CSD by
using the modified multiple platform method (MMPM) to establish an animal model
of CSD. Biochemical parameters such as levels of serum N-terminal propeptide of
type I procollagen (PINP), N-terminal cross-linking telopeptide of type I
collagen (NTX), growth hormone (GH), estradiol (E2), serum 25(OH)D, and calcium
(Ca) were evaluated at 0, 1, 2, and 3 months. After 3 months, each fourth lumbar
vertebra and the distal femoral metaphysis of the left extremity of rats were
harvested for micro-computed tomography scans and histological analysis,
respectively, after the rats were sacrificed under an overdose of pentobarbital
sodium. RESULTS: Compared with rats from the CON group, rats from the CSD group
showed significant decreases in bone mineral density (BMD), bone volume over
total volume, trabecular bone thickness, and trabecular bone number and
significant increases in bone surface area over bone volume and trabecular bone
separations (P < 0.05). Bone histomorphology studies showed that rats in the CSD
group had decreased osteogenesis, impaired mineralization of newly formed bones,
and deteriorative trabecular bone in the secondary spongiosa zone. In addition,
they showed significantly decreased levels of serum PINP (1 month later) and NTX
(3 months later) (P < 0.05). The serum 25(OH)D level of rats from the CSD group
was lower than that of rats from the CON group after 1 month (P < 0.05).
CONCLUSIONS: CSD markedly affects bone health by decreasing BMD and 25(OH)D,
deteriorating the bone microarchitecture, and decreasing bone formation and bone
resorption markers.
PMID- 27485746
TI - Foraging strategies of black-fronted titi monkeys (Callicebus nigrifrons) in
relation to food availability in a seasonal tropical forest.
AB - Many primates have to cope with a temporal scarcity in food availability that
shapes their foraging strategies. Here we investigated the changes in diet,
activity, and ranging behavior of a group of black-fronted titi monkeys
(Callicebus nigrifrons) according to the availability of the main high
nutritional-density item in their diet and the foraging strategy adopted when
this food is scarce. We monitored one habituated group using instantaneous scan
sampling over 1 year (533 h of observation, 61 days) in a seasonal tropical
forest fragment (245 ha). We simultaneously collected data on food availability
with fruit traps. The titi monkeys consumed fleshy fruits, the main high
nutritional-density item of their diet, in accordance with its availability, and
the availability of this item modulated the ingestion of vegetative plant parts,
a relatively low-nutritional-density food. During high fleshy fruit availability,
the titi monkeys consumed more fleshy fruits, flowers, and invertebrates. They
also traveled more, but concentrated their activity in a central area of their
home range. Conversely, during fleshy fruit scarcity, they increased the breadth
of their diet, switching to one richer in seeds and vegetative plant parts, and
with greater plant diversity. At the same time, they reduced most energy
demanding activities, traveling less and over shorter distances, but using their
home range more broadly. Corroborating the optimal foraging theory, titi monkeys
altered foraging strategies according to temporal food fluctuations and responded
to low fleshy fruit availability by changing their diet, activity, and ranging
behavior. The adoption of a low-cost/low-yield strategy allowed us to classify
them as energy minimizers.
PMID- 27485747
TI - Predatory threat of harpy eagles for yellow-breasted capuchin monkeys in the
Atlantic Forest.
AB - We describe seven encounters between different harpy eagle individuals (Harpia
harpyja) and a group of yellow-breasted capuchin monkeys (Sapajus xanthosternos)
in Una Biological Reserve. These interactions lasted 58 min on average. In each
of those encounters, the capuchin monkeys used particular behavioral strategies
against the harpy eagle that were not employed in reaction to other aerial
predators. We did not observe any successful predation events, but after one of
those encounters an infant disappeared from the capuchin group. As a whole, these
observations indicate that the presence of harpy eagles in the group's home range
increases predation risk for capuchin monkeys. The present report also suggests a
reoccupation by H. harpyja of this area, as no previous recent records identify
harpy eagle occurrence in Una Biological Reserve.
PMID- 27485748
TI - The first smile: spontaneous smiles in newborn Japanese macaques (Macaca
fuscata).
AB - Spontaneous smiles are facial movements that are characterized by lip corner
raises that occur during irregular sleep or drowsiness without known external or
internal causes. They are shown by human infants and infant chimpanzees. These
smiles are considered to be the developmental origin of smiling and laughter.
There are some case studies showing that spontaneous smiles occur in Japanese
macaques. The goals of this study were to investigate whether newborn Japanese
macaques show a considerable number of spontaneous smiles thus to examine the
mechanism of them. Seven newborn Japanese macaques were observed in a room for an
average of 44 min, and incidental sleeping situations were monitored twice. All
seven participants showed spontaneous smiles at least once during the
observation. They showed 8.29 spontaneous smiles in average (SD = 10.89; 58
smiles in total), all found in the state of REM sleep. Thirty-nine of the 58
smiles were produced on the left side of the mouth. These characteristics were
similar to those of spontaneous smiles in human infants. This is the first
evidence that macaques as well as hominoids show a considerable number of
spontaneous smiles. These phenomena may facilitate the development of the
zygomaticus major muscle, which is implicated in smiling-like facial expressions.
PMID- 27485749
TI - Adenosine A2A receptors in the olfactory bulb suppress rapid eye movement sleep
in rodents.
AB - Rapid eye movement (REM) sleep behavior disorder in humans is often accompanied
by a reduced ability to smell and detect odors, and olfactory bulbectomized rats
exhibit increased REM sleep, suggesting that the olfactory bulb (OB) is involved
in REM-sleep regulation. However, the molecular mechanism of REM-sleep regulation
by the OB is unknown. Adenosine promotes sleep and its A2A receptors (A2AR) are
expressed in the OB. We hypothesized that A2AR in the OB regulate REM sleep.
Bilateral microinjections of the A2AR antagonist SCH58261 into the rat OB
increased REM sleep, whereas microinjections of the A2AR agonist CGS21680
decreased REM sleep. Similar to the A2AR antagonist, selective A2AR knockdown by
adeno-associated virus carrying short-hairpin RNA for A2AR in the rat OB
increased REM sleep. Using chemogenetics on the basis of designer receptors
exclusively activated by designer drugs, we demonstrated that the inhibition of
A2AR neurons increased REM sleep, whereas the activation of these neurons
decreased REM sleep. Moreover, using a conditional anterograde axonal tract
tracing approach, we found that OB A2AR neurons innervate the piriform cortex and
olfactory tubercle. These novel findings indicate that adenosine suppresses REM
sleep via A2AR in the OB of rodents.
PMID- 27485750
TI - Mapping the connectivity of serotonin transporter immunoreactive axons to
excitatory and inhibitory neurochemical synapses in the mouse limbic brain.
AB - Serotonin neurons arise from the brainstem raphe nuclei and send their
projections throughout the brain to release 5-HT which acts as a modulator of
several neuronal populations. Previous electron microscopy studies in rats have
morphologically determined the distribution of 5-HT release sites (boutons) in
certain brain regions and have shown that 5-HT containing boutons form synaptic
contacts that are either symmetric or asymmetric. In addition, 5-HT boutons can
form synaptic triads with the pre- and postsynaptic specializations of either
symmetrical or asymmetrical synapses. However, due to the labor intensive
processing of serial sections required by electron microscopy, little is known
about the neurochemical properties or the quantitative distribution of 5-HT
triads within whole brain or discrete subregions. Therefore, we used a semi
automated approach that combines immunohistochemistry and high-resolution
confocal microscopy to label serotonin transporter (SERT) immunoreactive axons
and reconstruct in 3D their distribution within limbic brain regions. We also
used antibodies against key pre- (synaptophysin) and postsynaptic components of
excitatory (PSD95) or inhibitory (gephyrin) synapses to (1) identify putative 5
HTergic boutons within SERT immunoreactive axons and, (2) quantify their close
apposition to neurochemical excitatory or inhibitory synapses. We provide a 5
HTergic axon density map and have determined the ratio of synaptic triads
consisting of a 5-HT bouton in close proximity to either neurochemical excitatory
or inhibitory synapses within different limbic brain areas. The ability to model
and map changes in 5-HTergic axonal density and the formation of triadic
connectivity within whole brain regions using this rapid and quantitative
approach offers new possibilities for studying neuroplastic changes in the 5
HTergic pathway.
PMID- 27485752
TI - Estimating functional brain networks by incorporating a modularity prior.
AB - Functional brain network analysis has become one principled way of revealing
informative organization architectures in healthy brains, and providing sensitive
biomarkers for diagnosis of neurological disorders. Prior to any post hoc
analysis, however, a natural issue is how to construct "ideal" brain networks
given, for example, a set of functional magnetic resonance imaging (fMRI) time
series associated with different brain regions. Although many methods have been
developed, it is currently still an open field to estimate biologically
meaningful and statistically robust brain networks due to our limited
understanding of the human brain as well as complex noises in the observed data.
Motivated by the fact that the brain is organized with modular structures, in
this paper, we propose a novel functional brain network modeling scheme by
encoding a modularity prior under a matrix-regularized network learning
framework, and further formulate it as a sparse low-rank graph learning problem,
which can be solved by an efficient optimization algorithm. Then, we apply the
learned brain networks to identify patients with mild cognitive impairment (MCI)
from normal controls. We achieved 89.01% classification accuracy even with a
simple feature selection and classification pipeline, which significantly
outperforms the conventional brain network construction methods. Moreover, we
further explore brain network features that contributed to MCI identification,
and discovered potential biomarkers for personalized diagnosis.
PMID- 27485751
TI - Overall satisfaction of health care users with the quality of and access to
health care services: a cross-sectional study in six Central and Eastern European
countries.
AB - BACKGROUND: The measurement of consumer satisfaction is an essential part of the
assessment of health care services in terms of service quality and health care
system responsiveness. Studies across Europe have described various strategies
health care users employ to secure services with good quality and quick access.
In Central and Eastern European countries, such strategies also include informal
payments to health care providers. This paper analyzes the satisfaction of health
care users with the quality of and access to health care services. The study
focuses on six Central and Eastern European countries (Bulgaria, Hungary,
Lithuania, Poland, Romania and Ukraine). METHODS: We use data on past experience
with health care use collected in 2010 through uniform national surveys in these
countries. Based on these data, we carry out a multi-country analysis to
investigate factors associated with the satisfaction of health care users in the
six countries. RESULTS: The results indicate that about 10-14 % of the service
users are not satisfied with the quality of, or access to health care services
they used in the preceding year. However, significant differences across
countries and services are observed, e.g. the highest level of dissatisfaction
with access to outpatient services (16.4 %) is observed among patients in
Lithuania, while in Poland, the level of dissatisfaction with quality of
outpatient and inpatient services are much lower than dissatisfaction with
access. The study also analyses the association of users' satisfaction with
factors such as making informal payments, inability to pay and relative
importance of service attributes stated by the service users. CONCLUSIONS: These
multi-country findings provide evidence for health policy making in the Central
and Eastern European countries. Although the average rates of satisfactions per
country are relatively high, the results suggest that there is ample room for
improvements. Specifically, many service-users still report dissatisfaction
especially those who pay informally and those unable to pay. The high shares of
informal payments and inability of users to deal with the health expenditures
lead to doubts about the fairness of the health care provision in Central and
Eastern Europe. There is an urgent need for policy makers in the region to not
only acknowledge but also to effectively address this key problem.
PMID- 27485754
TI - Analytical and empirical fluctuation functions of the EEG microstate random walk
Short-range vs. long-range correlations.
AB - We analyze temporal autocorrelations and the scaling behaviour of EEG microstate
sequences during wakeful rest. We use the recently introduced random walk
approach and compute its fluctuation function analytically under the null
hypothesis of a short-range correlated, first-order Markov process. The empirical
fluctuation function and the Hurst parameter H as a surrogate parameter of long
range correlations are computed from 32 resting state EEG recordings and for a
set of first-order Markov surrogate data sets with equilibrium distribution and
transition matrices identical to the empirical data. In order to distinguish
short-range correlations (H ~ 0.5) from previously reported long-range
correlations (H > 0.5) statistically, confidence intervals for H and the
fluctuation functions are constructed under the null hypothesis. Comparing three
different estimation methods for H, we find that only one data set consistently
shows H > 0.5, compatible with long-range correlations, whereas the majority of
experimental data sets cannot be consistently distinguished from Markovian
scaling behaviour. Our analysis suggests that the scaling behaviour of resting
state EEG microstate sequences, though markedly different from uncorrelated, zero
order Markov processes, can often not be distinguished from a short-range
correlated, first-order Markov process. Our results do not prove the microstate
process to be Markovian, but challenge the approach to parametrize resting state
EEG by single parameter models.
PMID- 27485753
TI - Down but not out in posterior cingulate cortex: Deactivation yet functional
coupling with prefrontal cortex during demanding semantic cognition.
AB - The posterior cingulate cortex (pCC) often deactivates during complex tasks, and
at rest is often only weakly correlated with regions that play a general role in
the control of cognition. These observations led to the hypothesis that pCC
contributes to automatic aspects of memory retrieval and cognition. Recent work,
however, has suggested that the pCC may support both automatic and controlled
forms of memory processing and may do so by changing its communication with
regions that are important in the control of cognition across multiple domains.
The current study examined these alternative views by characterising the
functional coupling of the pCC in easy semantic decisions (based on strong global
associations) and in harder semantic tasks (matching words on the basis of
specific non-dominant features). Increasingly difficult semantic decisions led to
the expected pattern of deactivation in the pCC; however, psychophysiological
interaction analysis revealed that, under these conditions, the pCC exhibited
greater connectivity with dorsolateral prefrontal cortex (PFC), relative to both
easier semantic decisions and to a period of rest. In a second experiment using
different participants, we found that functional coupling at rest between the pCC
and the same region of dorsolateral PFC was stronger for participants who were
more efficient at semantic tasks when assessed in a subsequent laboratory
session. Thus, although overall levels of activity in the pCC are reduced during
external tasks, this region may show greater coupling with executive control
regions when information is retrieved from memory in a goal-directed manner.
PMID- 27485755
TI - Feasibility and potential limitations of abbreviated breast MRI: an observer
study using an enriched cohort.
AB - BACKGROUND: Breast cancer screening using magnetic resonance imaging (MRI) has
been introduced in Western countries primarily for populations with an elevated
risk of breast cancer. We conducted an observer study involving an experimental
abbreviated MRI interpretation by Japanese radiologists, using an enriched
cohort, to evaluate its feasibility in a screening setting. METHODS: Eighty-eight
breast MRI examinations including 28 cases with breast cancer were enrolled as
study subjects. Two radiologists independently reviewed the MR images, first with
only two sequences (abbreviated series), and then with all of the images provided
for clinical care (full diagnostic series). The difference in sensitivity and
specificity was evaluated using McNemar's test. Interobserver agreement was
assessed by calculating kappa values. RESULTS: A total of 176 breasts including
31 cancers (3 cases with bilateral disease) were included. No significant
difference in sensitivity or specificity for either observer was observed between
the abbreviated series and the full diagnostic series (observer 1: sensitivity
87.1 vs 87.1 %, p = 1.00, specificity 91.7 vs 90.3 %, p = 0.791; observer 2:
sensitivity 93.5 vs 96.8 %, p = 1.00, specificity 83.4 vs 89.7 %, p = 0.064).
Moderate interobserver agreement (kappa = 0.56) was observed for the abbreviated
series, whereas substantial agreement (kappa = 0.69) was observed for the full
diagnostic series. CONCLUSIONS: The diagnostic accuracy of the abbreviated breast
MRI was not inferior to that of the conventional full diagnostic interpretation,
although a slight decline in interobserver agreement was observed.
PMID- 27485756
TI - Therapeutic play to prepare children for invasive procedures: a systematic
review.
AB - OBJECTIVE: To analyze the available evidence regarding the efficacy of using
therapeutic play on behavior and anxiety in children undergoing invasive
procedures. DATA SOURCE: The systematic review search was performed in the
MEDLINE, LILACS, CENTRAL and CINAHL databases. There was no limitation on the
year or language. SYNTHESIS OF DATA: The literature search found 1892 articles
and selected 22 for full reading. Eight articles were excluded, as they did not
address the objectives assessed in this review. Twelve studies, representing 14
articles, were included. The studies were conducted between 1983 and 2015, five
in Brazil, one in the United States, five in China, one in Lebanon, one in
Taiwan, and one in Iran. Most studies showed that intervention with therapeutic
play promotes reduction in the level of anxiety and promotes collaborative
behavior and acceptance of the invasive procedure. CONCLUSIONS: Evidence related
to the use of therapeutic play on anxiety and behavior of children undergoing
invasive procedures is still questionable. The absence, in most studies, of the
creation of a random sequence to assign the subjects to either the control or the
experimental group, as well as allocation concealment, are factors that
contribute to these questions. Another issue that characterizes an important
source of bias is the absence of blinded evaluators. It is necessary to perform
further studies that will take into account greater methodological stringency.
PMID- 27485757
TI - The influence of home-rearing environment on children's behavioral problems 3
years' later.
AB - Reduction of children's behavioral problems has the potential to ameliorate
parental stress, mental health problems, and family dysfunction. The current
study was designed as a 3-year longitudinal study with secondary data. A total of
99 caregivers with preschool aged children were required to complete two self
reported questionnaires: the Index of Child Care Environment and Strengths and
Difficulties Questionnaire. It demonstrated that a positive home-rearing
environment had a positive influence on children's behavioral problem 3 years'
later. Our study suggests that we may reduce behavioral problems in children's
later development by providing a positive home rearing environment.
PMID- 27485758
TI - Grafting of mesenchymal stem cell-seeded small intestinal submucosa to repair the
deep partial-thickness burns.
AB - PURPOSE: Regenerative medicine provides many treatments for burn wounds, of which
cell-seeded substitutes are encouraging for large and deep burns. To assess the
feasibility of mesenchymal stem cell (MSC)-seeded small intestinal submucosa
(SIS) to repair the deep partial-thickness burns, a rat study was performed.
MATERIALS & METHODS: The burn model was created by contacting the dorsal surface
directly with boiled water for 10 seconds. MSCs at passage 3 were seeded on the
SIS before implantation. Three days after burn injury, the grafts were implanted
onto the burn area. At 3, 7, 14 and 21 days post implantation, gross observation
and histological assessments were performed. RESULTS: SIS alone and MSC-seeded
SIS were able to accelerate the burn wound closure by enhancing granulation
tissue formation, increasing wound maturity, improving revascularization, and
inducing the proliferation of neo-epidermal cells. Additionally, MSC-seeded SIS
was much more effective than SIS alone for the repair of deep partial-thickness
burns. CONCLUSION: Both SIS and MSC-seeded SIS were able to repair the large and
deep burn wounds and the loaded MSCs possessed positive effects to accelerate the
wound closure in a rat model.
PMID- 27485759
TI - Combinatorial fabrication of composite nanorods using oblique angle co
deposition.
AB - We demonstrate that oblique angle co-deposition can be used as a versatile
combinatory nanofabrication technique to generate a library of nanomaterials.
Using the Cu-Fe2O3 system as an example, by carefully characterizing the vapor
plumes of the source materials, a composition map can be generated, which is used
to design the locations of all the substrate holders. The resulting
nanostructures at different locations show different thickness, morphology,
crystallinity, composition, as well as inhomogeneity in microstructures, and
material maps of all these structural parameters are established. By further
oxidizing or reducing the composite nanostructures, their properties-such as band
gap, photocatalytic performance, and magnetic properties-can be easily linked to
their composition and other structural parameters. Optimal materials for
photocatalytic and magnetic applications are efficiently identified. It is
expected that oblique angle co-deposition and its variations could become the
most powerful combinatory nanofabrication technique for nanomaterial survey.
PMID- 27485760
TI - Diagnosis of bacterial pathogens in the dialysate of peritoneal dialysis patients
with peritonitis using surface-enhanced Raman spectroscopy.
AB - BACKGROUND: Bacterial peritonitis is the most common cause of peritoneal dialysis
(PD) therapy drop-out. A quick and accurate diagnosis of the bacterial pathogen
can reduce the PD drop-out rate. Surface-enhanced Raman spectroscopy (SERS) can
rapidly identify bacteria using chips coated with nano-sized metal particles.
METHODS: Known bacteria were loaded in the SERS-chips and illuminated with laser
light to establish a reference Raman spectra library. Dialysate from PD
peritonitis patients was concentrated by centrifuge and examined with the same
SERS, and the resulting Raman spectra were compared with library spectra for
bacteria identification. Principal component analysis was used for further
confirmation. The same batches of dialysate were sent to routine culture as a
reference bacteria identification method. The results of the 2 identification
methods were compared. RESULTS: A total of 43 paired-samples were sent for study.
There were 37 samples with bacteria identified but 6 were culture-negative by the
reference method. 31 bacteria were identified in paired-samples by SERS, among
which, 29 bacteria were exactly the same as those identified by the reference
method. Bacteria not included in the reference library spectra cannot be
identified. CONCLUSIONS: SERS techniques can rapidly identify bacterial pathogens
in the dialysate of PD peritonitis patients.
PMID- 27485761
TI - A novel MSX1 intronic mutation associated with autosomal dominant non-syndromic
oligodontia in a large Chinese family pedigree.
AB - BACKGROUND: Tooth agenesis is a common developmental dental anomaly. The aim of
the study was to identify the causal genetic mutation in a four-generation
Chinese family affected with non-syndromic autosomal dominant tooth agenesis.
METHODS: Genome-wide scanning was performed using the Illumina Linkage-12 array.
Genotyping of short tandem repeat markers was used to finely map the causative
locus. Haplotype analysis and Sanger sequencing was performed to precisely locate
the position and nature of the gene defect. RESULTS: Clinical examination of the
available 23 family members showed variable tooth agenesis in 10 subjects,
ranging from oligodontia to mild hypodontia. Genome-wide scanning and haplotype
analyses identified the 4p16.1-p16.3 region with a maximum multi-point LOD score
of 3.50, which overlapped with the MSX1 gene. A single heterozygous point
mutation IVS1-5 G>A in the MSX1 gene was exclusively detected in the 10 family
members affected with tooth agenesis. Sequencing of MSX1 cDNA revealed that the
intronic mutation did not affect the normal splicing pattern of the pre-mRNA.
However, real-time qPCR analysis of lymphocyte RNA showed that the level of MSX1
mRNA was significantly decreased in individuals heterozygous for the mutation.
CONCLUSIONS: We identified and characterized a novel intronic mutation in the
MSX1 gene in a large Chinese pedigree, adding to the small repertoire of MSX1
mutations associated with autosomal dominant tooth agenesis. We hypothesize that
the variable degree of tooth agenesis observed in each affected individual may be
due to sub-optimal levels of MSX1 expression during critical stages tooth
development.
PMID- 27485762
TI - "That Should Be Left to Doctors, That's What They are There For!"-Exploring the
Reflexivity and Trust of Young Adults When Seeking Health Information.
AB - This paper explores the health information-seeking practices of healthy young
adults and how they assess and rank sources of information through a qualitative
study. The findings show that participants (a) are strongly committed to
searching for information about health and lifestyle, especially via the
Internet; (b) healthcare professionals were perceived as the most reliable source
of health information and advice; (c) online health information, although
frequently accessed and experienced as empowering, is seen as a potentially
unreliable source. Findings evidence how becoming better informed about health
related topics plays a pivotal role in individuals' lives, most notably by using
the Internet. Participants were able to reflect about what it means to know about
health. The construction of trust regarding health information involved a
heuristic process vis-a-vis source reliability and perceived credibility that
places doctors as the most trustworthy medium of medical advice and health
information. We conclude that participants' trust toward professionals suggests
the preference and need for more personalized care; and it is a response to the
ambiguity and uncertainty that permeates the health information landscape,
particularly that which is web-based.
PMID- 27485763
TI - A Bayesian Power Analysis Procedure Considering Uncertainty in Effect Size
Estimates from a Meta-analysis.
AB - In conventional frequentist power analysis, one often uses an effect size
estimate, treats it as if it were the true value, and ignores uncertainty in the
effect size estimate for the analysis. The resulting sample sizes can vary
dramatically depending on the chosen effect size value. To resolve the problem,
we propose a hybrid Bayesian power analysis procedure that models uncertainty in
the effect size estimates from a meta-analysis. We use observed effect sizes and
prior distributions to obtain the posterior distribution of the effect size and
model parameters. Then, we simulate effect sizes from the obtained posterior
distribution. For each simulated effect size, we obtain a power value. With an
estimated power distribution for a given sample size, we can estimate the
probability of reaching a power level or higher and the expected power. With a
range of planned sample sizes, we can generate a power assurance curve. Both the
conventional frequentist and our Bayesian procedures were applied to conduct
prospective power analyses for two meta-analysis examples (testing standardized
mean differences in example 1 and Pearson's correlations in example 2). The
advantages of our proposed procedure are demonstrated and discussed.
PMID- 27485765
TI - Intrapair Comparison of Life-Course Appetite and Physical Activity in Elderly
Danish Twins: Reliability and Association With Subsequent Survival.
AB - Avoiding overeating and being physically active is associated with healthy aging,
but methodological issues challenge the quantification of the association.
Intrapair comparison of twins is a study design that attempts to minimize social
norm-driven biased self-reporting of lifestyle factors. We aimed to investigate
the association between self-reported lifestyle factors and subsequent survival
in 347 Danish twin pairs aged 70 years and older and, additionally, to
investigate the reliability of these self-reports. The twins were interviewed in
2003 and followed for mortality until 2015. They were asked to compare their
appetite and physical activity to that of their co-twins in different stages of
life. On an individual level, we found a positive association between current
self-reported physical activity and late-life survival for elderly twins. This
was supported by the intrapair analyses, which revealed a positive association
between midlife and current physical activity and late-life survival. A positive
association between lower appetite and late-life survival was found generally
over the life course in the individual level analyses but not in the intrapair
analyses. Kappa values for the inter-twin agreement on who ate the most were 0.16
to 0.34 in different life stages, and for physical activity 0.19 to 0.26,
corresponding to a slight-to-fair agreement. Approximately, 50% of the twin pairs
were not in agreement regarding physical activity, and of these twins 75% (95%
CI: 67-82%) considered themselves the most active twin. These findings indicate a
still-existing tendency of answering according to social norms, even in a twin
study designed to minimize this.
PMID- 27485766
TI - Tendon reflex is suppressed during whole-body vibration.
AB - In this study we have investigated the effect of whole body vibration (WBV) on
the tendon reflex (T-reflex) amplitude. Fifteen young adult healthy volunteer
males were included in this study. Records of surface EMG of the right soleus
muscle and accelerometer taped onto the right Achilles tendon were obtained while
participant stood upright with the knees in extension, on the vibration platform.
Tendon reflex was elicited before and during WBV. Subjects completed a set of
WBV. Each WBV set consisted of six vibration sessions using different frequencies
(25, 30, 35, 40, 45, 50Hz) applied randomly. In each WBV session the Achilles
tendon was tapped five times with a custom-made reflex hammer. The mean peak-to
peak (PP) amplitude of T-reflex was 1139.11+/-498.99uV before vibration. It
decreased significantly during WBV (p<0.0001). The maximum PP amplitude of T
reflex was 1333+/-515MUV before vibration. It decreased significantly during WBV
(p<0.0001). No significant differences were obtained in the mean acceleration
values of Achilles tendon with tapping between before and during vibration
sessions. This study showed that T-reflex is suppressed during WBV. T-reflex
suppression indicates that the spindle primary afferents must have been pre
synaptically inhibited during WBV similar to the findings in high frequency
tendon vibration studies.
PMID- 27485764
TI - TGF-beta1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.
AB - Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia
(ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation.
However, there has not been an adequate system to explore the mechanisms of human
ADM induction. We have developed a flow cytometry-based, high resolution lineage
tracing method and 3D culture system to analyse ADM in human cells. In this
system, well-known mouse ADM inducers did not promote ADM in human cells. In
contrast, TGF-beta1 efficiently converted human acinar cells to duct-like cells
(AD) in a SMAD-dependent manner, highlighting fundamental differences between the
species. Functionally, AD cells gained transient proliferative capacity.
Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did
sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires
ADM-associated-changes to promote PDAC initiation. This ADM model provides a
novel platform to explore the mechanisms involved in the development of human
pancreatic diseases.
PMID- 27485767
TI - Women's experiences with HIV-related stigma from health care providers in Lima,
Peru: "I would rather die than go back for care".
AB - In Peru, HIV/AIDS is increasing among heterosexual women. In this qualitative
study researchers examined HIV-related stigma among 14 women in Lima, Peru, who
were HIV positive and at least 18 years of age. Data were analyzed using thematic
analysis and indicated that women experienced stigma from health care providers.
Two broad themes emerged from the data: forms of stigma and response to stigma.
Within these themes, subthemes included maltreatment during care, neglect of
patients' rights to confidentiality and privacy, and the process of women
speaking out. Stigma from health care providers had a long-term, negative impact
on women's willingness to seek treatment. Future stigma reduction initiatives, on
a global level, should include health care workers.
PMID- 27485768
TI - Variation of excited-state dynamics in trifluoromethyl functionalized C60
fullerenes.
AB - We report on electronically excited-state dynamics of three different
trifluoromethyl C60 fullerenes (TMFs, C60(CF3)n: C60/4-1, C60/6-2, and C60/10-1,
featuring four, six, and ten trifluoromethyl groups, respectively) using steady
state and time-resolved optical spectroscopy as well as ultrafast pump/probe
transient absorption spectroscopy. C60/4-1 and C60/6-2 dissolved in toluene
solvent show near-unity S1 -> T1 intersystem crossing quantum yield (PhiISC), ca.
1 ns S1-state lifetimes, and microsecond-timescale T1-state lifetimes, which are
typical of the fullerene class. On the other hand, C60/10-1 exhibits a dominant
sub-nanosecond nonradiative S1 -> S0 relaxation mechanism and negligible PhiISC,
therefore decreasing the average excited-state lifetime (tauavg) by about 5
orders of magnitude compared to that of C60/4-1 and C60/6-2 (tauavg ~ 17 MUs and
54 MUs for C60/4-1 and C60/6-2, respectively, whereas tauavg ~ 100 ps for C60/10
1). These excited-state characteristics of C60/4-1 and C60/6-2 are preserved in
polymer matrix, suggesting that fullerene/polymer interactions do not modulate
intrinsic photophysics of trifluoromethyl-substituted fullerenes. The contrasting
excited-state study results of C60/4-1 and C60/6-2 to that of C60/10-1 infer that
intrinsic optical properties and excited-state dynamics can be affected by the
substitution on the fullerene.
PMID- 27485769
TI - 5-Hydroxymethylcytosine in E-box motifs ACAT|GTG and ACAC|GTG increases DNA
binding of the B-HLH transcription factor TCF4.
AB - We evaluated DNA binding of the B-HLH family members TCF4 and USF1 using protein
binding microarrays (PBMs) containing double-stranded DNA probes with cytosine on
both strands or 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) on one
DNA strand and cytosine on the second strand. TCF4 preferentially bound the E-box
motif (CAN|NTG) with strongest binding to the 8-mer CAG|GTGGT. 5mC uniformly
decreases DNA binding of both TCF4 and USF1. The bulkier 5hmC also inhibited USF1
binding to DNA. In contrast, 5hmC dramatically enhanced TCF4 binding to E-box
motifs ACAT|GTG and ACAC|GTG, being better bound than any 8-mer containing
cytosine. Examination of X-ray structures of the closely related TCF3 and USF1
bound to DNA suggests TCF3 can undergo a conformational shift to preferentially
bind to 5hmC while the USF1 basic region is bulkier and rigid precluding a
conformation shift to bind 5hmC. These results greatly expand the regulatory DNA
sequence landscape bound by TCF4.
PMID- 27485770
TI - Stakeholder analysis for the development of a community pharmacy service aimed at
preventing cardiovascular disease.
AB - BACKGROUND: Participatory approaches involving stakeholders across the health
care system can help enhance the development, implementation and evaluation of
health services. These approaches may be particularly useful in planning
community pharmacy services and so overcome challenges in their implementation
into practice. Conducting a stakeholder analysis is a key first step since it
allows relevant stakeholders to be identified, as well as providing planners a
better understanding of the complexity of the health care system. OBJECTIVES: The
main aim of this study was to conduct a stakeholder analysis to identify those
individuals and organizations that could be part of a leading planning group for
the development of a community pharmacy service (CPS) to prevent cardiovascular
disease (CVD) in Australia. METHODS: An experienced facilitator conducted a
workshop with 8 key informants of the Australian health care system. Two
structured activities were undertaken. The first explored current needs and gaps
in cardiovascular care and the role of community pharmacists. The second was a
stakeholder analysis, using both ex-ante and ad-hoc approaches. Identified
stakeholders were then classified into three groups according to their relative
influence on the development of the pharmacy service. The information gathered
was analyzed using qualitative content analysis. RESULTS: The key informants
identified 46 stakeholders, including (1) patient/consumers and their
representative organizations, (2) health care providers and their professional
organizations and (3) institutions and organizations that do not directly
interact with patients but organize and manage the health care system, develop
and implement health policies, pay for health care, influence funding for health
service research or promote new health initiatives. From the 46 stakeholders, a
core group of 12 stakeholders was defined. These were considered crucial to the
service's development because they held positions that could drive or inhibit
progress. Secondary results of the workshop included: a list of needs and gaps in
cardiovascular care (n = 6), a list of roles for community pharmacists in
cardiovascular prevention (n = 12) and a list of potential factors (n = 7) that
can hinder the integration of community pharmacy services into practice.
CONCLUSIONS: This stakeholder analysis provided a detailed picture of the wide
range of stakeholders across the entire health care system that have a stake in
the development of a community pharmacy service aimed at preventing CVD. Of
these, a core group of key stakeholders, with complementary roles, can then be
approached for further planning of the service. The results of this analysis
highlight the relevance of establishing multilevel stakeholder groups for CPS
planning.
PMID- 27485771
TI - Systematic Identification of Matching Molecular Series and Mapping of Screening
Hits.
AB - Matching molecular series (MMS) have originally been introduced as an extension
of the matched molecular pair (MMP) concept to facilitate the design of
substructure-based structure-activity relationship (SAR) networks. An MMP is
defined as a pair of compounds that only differ by a structural change at a
single site. In addition, an MMS is defined as an MMP-based series of compounds
that have a conserved structural core and are distinguished by modifications at a
single site. Systematic generation of MMS from specifically active compounds
generalizes the search for series of structural analogs. Potency-ordered MMS
provide series associated with SAR information. We have systematically extracted
MMS from publicly available compounds with well-defined activity measurements and
generated a large database with approx. 40 000 single- and 13 600 multi-target
series, which provide a rich source of SAR information. As an application, we
introduce MMP-based mapping of screening hits to MMS to search for initial SAR
information and determine all SAR environments available for such hits. The MMS
database is made freely available to the scientific community.
PMID- 27485772
TI - Identification of Novel Histamine H4 Ligands by Virtual Screening on Molecular
Dynamics Ensembles.
AB - We report the identification of novel histamine H4 receptor ligands by ensemble
docking on homology model conformers derived from molecular dynamics simulations.
Selected receptor models from the trajectories demonstrated superior virtual
screening performance compared to the initial models. The ensemble of the best
models was able to retrieve a diverse set of known H4 ligands. Prospective
virtual screening against these models and subsequent in vitro experimental
validation identified novel H4 ligands. Compound 3 showing highest affinity and
ligand efficiency represents an interesting scaffold for further medicinal
chemistry exploration.
PMID- 27485773
TI - Topological Fingerprints as an Aid in Finding Structural Patterns for LRRK2
Inhibition.
AB - Multiplet-based fingerprint mapping has been used to analyse the relationship
between the structural features of potential drug candidates and the enzyme LRRK2
inhibition expressed as the inhibition constant (pKi ). For 198 structurally
diverse compounds 4195 dimensional fingerprints were generated and mathematically
manipulated using partial least squares (PLS) regression. A variation of PLS-BETA
technique was developed for the reduction of noise by eliminating excess
variables that resulted in a 636 dimensional fingerprint related to pKi . The
QSAR model for the training set of 170 compounds (R(2) =0.87, Q(2) =0.77 and
SDEC=0.42) had four latent variables (PLS components) and it was validated by the
external test set of 28 compounds (Qext (2) =0.63). The proposed model of LRRK2
inhibitory activity can be helpful in designing focused libraries enriched in
LRRK2 inhibitors and identifying new active chemotypes in compound databases.
PMID- 27485774
TI - LECTINPred: web Server that Uses Complex Networks of Protein Structure for
Prediction of Lectins with Potential Use as Cancer Biomarkers or in Parasite
Vaccine Design.
AB - Lectins (Ls) play an important role in many diseases such as different types of
cancer, parasitic infections and other diseases. Interestingly, the Protein Data
Bank (PDB) contains +3000 protein 3D structures with unknown function. Thus, we
can in principle, discover new Ls mining non-annotated structures from PDB or
other sources. However, there are no general models to predict new biologically
relevant Ls based on 3D chemical structures. We used the MARCH-INSIDE software to
calculate the Markov-Shannon 3D electrostatic entropy parameters for the complex
networks of protein structure of 2200 different protein 3D structures, including
1200 Ls. We have performed a Linear Discriminant Analysis (LDA) using these
parameters as inputs in order to seek a new Quantitative Structure-Activity
Relationship (QSAR) model, which is able to discriminate 3D structure of Ls from
other proteins. We implemented this predictor in the web server named LECTINPred,
freely available at http://bio-aims.udc.es/LECTINPred.php. This web server showed
the following goodness-of-fit statistics: Sensitivity=96.7 % (for Ls),
Specificity=87.6 % (non-active proteins), and Accuracy=92.5 % (for all proteins),
considering altogether both the training and external prediction series. In mode
2, users can carry out an automatic retrieval of protein structures from PDB. We
illustrated the use of this server, in operation mode 1, performing a data mining
of PDB. We predicted Ls scores for +2000 proteins with unknown function and
selected the top-scored ones as possible lectins. In operation mode 2, LECTINPred
can also upload 3D structural models generated with structure-prediction tools
like LOMETS or PHYRE2. The new Ls are expected to be of relevance as cancer
biomarkers or useful in parasite vaccine design.
PMID- 27485775
TI - Global Model for Octanol-Water Partition Coefficients from Proton Nuclear
Magnetic Resonance Spectra.
AB - The ability to estimate chemical and physical properties from experimental
spectra is highly desirable, as it eliminates the need for a priori knowledge of
exact chemical structure and allows the property estimation of mixtures. Here we
report the proof of principle that a predictive method for octanol-water
partition coefficient (logP) based on (1) H-NMR spectra in d(3) -chloroform is
feasible and can yield accuracy comparable to in silico logP models. The
Spectrometric Data-Activity Relationship (QSDAR) reported predicts logP of
neutral organic chemicals using descriptors derived only from (1) H-NMR chemical
shifts, integrations and peak widths. Proton NMR spectra of 140 compounds with
diverse structures were used to construct a Multiple Linear Regression (MLR) and
a Partial Least Squares (PLS) model that predicts logP. The optimized models were
internally validated by K-fold cross validation and leave-one-out validation, and
externally with a test set of 28 chemicals. The squared regression coefficients
of prediction for the MLR and PLS regression models were 0.970 and 0.971
respectively, showing that the method allows accurate prediction of logP values
exclusively from predicted (1) H NMR spectra.
PMID- 27485776
TI - Discovery and Bioevaluation of Novel Pyrazolopyrimidine Analogs as Competitive
Hsp90 Inhibitors Through Shape-Based Similarity Screening.
AB - Hsp90 as a promising therapeutic target for the treatment of cancer has received
great attention. Many Hsp90 inhibitors such as BIIB021 and CUDC-305 have been in
clinical. In this paper shape-based similarity screening through ROCS overlays on
the basis of CUDC-305, BIIB021, PU-H71 and PU-3 were performed to discover HSP90
inhibitors. A set of 19 novel pyrazolopyrimidine analogues was identified and
evaluated on enzyme level and cell-based level as Hsp90 inhibitors. The compound
HDI4-04 with IC50 0.35 uM in the Hsp90 ATP hydrolysis assay exhibited potent
cytotoxicity against five human cancer cell lines. Western blot analysis and
Hsp70 luciferase reporter assay further confirmed that HDI4-04 targeted the Hsp90
protein folding machinery. And according to the biological assay, the SAR was
discussed and summarized, which will guide us for further optimization of these
compounds.
PMID- 27485777
TI - External Evaluation of QSAR Models, in Addition to Cross-Validation: Verification
of Predictive Capability on Totally New Chemicals.
PMID- 27485778
TI - PRDM5 promotes the proliferation and invasion of murine melanoma cells through up
regulating JNK expression.
AB - PRDM (PRDI-BF1 and RIZ domain-containing) proteins constitute a family of zinc
finger proteins and play important roles in multiple cellular processes by acting
as epigenetic modifiers. PRDM5 is a recently identified member of the PRDM family
and may function as a tumor suppressor in several types of cancer. However, the
role of PRDM5 in murine melanoma remains largely unknown. In our study, effect of
PRDM5 on murine melanoma cells was determined and results showed that PRDM5
overexpression significantly promoted proliferation, migration, and invasion of
murine melanoma B16F10 cells. Consistently, silencing of PRDM5 expression
significantly inhibited proliferation, invasion, and migration of B16F10 cells.
In vivo study also showed that PRDM5 silencing significantly inhibited the growth
and metastasis of melanoma in mice. PRDM5 was then found to increase the
expression and activation of JNK in B16F10 cells. JNK silencing significantly
reduced PRDM5-mediated up-regulation of JNK expression and blocked the PRDM5
induced proliferation and invasion of B16F10 cells. To further verify the
involvement of JNK signaling in PRDM5-induced progression of B16F10 cells, a
specific JNK inhibitor was employed to inhibit the JNK signaling pathway, and
results showed that PRDM5-induced proliferation and invasion of B16F10 cells were
abolished. We conclude that PRDM5 promotes the proliferation and invasion of
murine melanoma cells through up-regulating JNK expression and strategies
targeting PRDM5 may be promising for the therapy of melanoma.
PMID- 27485779
TI - Engineering Intracellular Delivery Nanocarriers and Nanoreactors from Oxidation
Responsive Polymersomes via Synchronized Bilayer Cross-Linking and Permeabilizing
Inside Live Cells.
AB - Reactive oxygen species (ROS) and oxidative stress are implicated in various
physiological and pathological processes, and this feature provides a vital
biochemical basis for designing novel therapeutic and diagnostic nanomedicines.
Among them, oxidation-responsive micelles and vesicles (polymersomes) of
amphiphilic block copolymers have been extensively explored; however, in previous
works, oxidation by ROS including H2O2 exclusively leads to microstructural
destruction of polymeric assemblies. For oxidation-responsive polymersomes, fast
release of encapsulated hydrophilic drugs and bioactive macromolecules will occur
upon microstructural disintegration. Under certain application circumstances,
this does not meet design requirements for sustained-release drug nanocarriers
and long-acting in vivo nanoreactors. Also note that conventional polymersomes
possess thick hydrophobic bilayers and compromised membrane permeability,
rendering them as ineffective nanocarriers and nanoreactors. We herein report the
fabrication of oxidation-responsive multifunctional polymersomes exhibiting
intracellular milieu-triggered vesicle bilayer cross-linking, permeability
switching, and enhanced imaging/drug release features. Mitochondria-targeted H2O2
reactive polymersomes were obtained through the self-assembly of amphiphilic
block copolymers containing arylboronate ester-capped self-immolative side
linkages in the hydrophobic block, followed by surface functionalization with
targeting peptides. Upon cellular uptake, intracellular H2O2 triggers cascade
decaging reactions and generates primary amine moieties; prominent amidation
reaction then occurs within hydrophobic bilayer membranes, resulting in
concurrent cross-linking and hydrophobic-to-hydrophilic transition of polymersome
bilayers inside live cells. This process was further utilized to achieve
integrated functions such as sustained drug release, (combination) chemotherapy
monitored by fluorescence and magnetic resonance (MR) imaging turn-on, and to
construct intracellular fluorogenic nanoreactors for cytosolic thiol-containing
bioactive molecules.
PMID- 27485781
TI - Polycyclic aromatic hydrocarbons (PAHs) in surface sediments from the intertidal
zone of Bohai Bay, Northeast China: Spatial distribution, composition, sources
and ecological risk assessment.
AB - Polycyclic aromatic hydrocarbons (PAHs) can enter intertidal zones by various
pathways and pose potential threats to intertidal ecosystem. We investigated
distribution, composition, sources and risk assessment of PAHs in intertidal
surface sediments of Bohai Bay. Total PAH concentrations ranged from 37.2ng.g-1
to 206.6ng.g-1, among which high values occurred near Nanpaishuihe River Estuary
and Haihe River Estuary. The composition patterns of PAHs were characterized by
the predominance of 3-ring and 4-ring PAHs, and acenaphthylene was the most
dominant component. Diagnostic ratios and principal component analysis have
confirmed that PAH contaminants originated from mixed sources, and the major was
local combustion. The mean benzo(a)pyrene equivalent concentration of total PAHs
in intertidal sediments was 15.67ng.g-1, which was mostly contributed by seven
carcinogenic PAHs. According to ecological risk assessment, negative effects
related to acenaphthylene would occur occasionally in partial survey regions of
the study.
PMID- 27485780
TI - The Microbiome of Aseptically Collected Human Breast Tissue in Benign and
Malignant Disease.
AB - Globally breast cancer is the leading cause of cancer death among women. The
breast consists of epithelium, stroma and a mucosal immune system that make up a
complex microenvironment. Growing awareness of the role of microbes in the
microenvironment recently has led to a series of findings important for human
health. The microbiome has been implicated in cancer development and progression
at a variety of body sites including stomach, colon, liver, lung, and skin. In
this study, we assessed breast tissue microbial signatures in intraoperatively
obtained samples using 16S rDNA hypervariable tag sequencing. Our results
indicate a distinct breast tissue microbiome that is different from the
microbiota of breast skin tissue, breast skin swabs, and buccal swabs.
Furthermore, we identify distinct microbial communities in breast tissues from
women with cancer as compared to women with benign breast disease. Malignancy
correlated with enrichment in taxa of lower abundance including the genera
Fusobacterium, Atopobium, Gluconacetobacter, Hydrogenophaga and Lactobacillus.
This work confirms the existence of a distinct breast microbiome and differences
between the breast tissue microbiome in benign and malignant disease. These data
provide a foundation for future investigation on the role of the breast
microbiome in breast carcinogenesis and breast cancer prevention.
PMID- 27485782
TI - Microbial community structure shifts are associated with temperature, dispersants
and nutrients in crude oil-contaminated seawaters.
AB - This study tracked structure shifts of bacterial compositions before, during and
after invading by crude oil to determine the microbial response and explore how
temperature, dispersants and nutrients affect the composition of microbial
communities or their activities of biodegradation in artificial marine
environment. During petroleum hydrocarbons exposed, the composition and
functional dynamics of marine microbial communities were altered, favoring
bacteria that could utilize this rich carbon source such as the Proteobacteria,
Firmicutes, Actinobacteria and Bacteroidetes phyla. Low temperature as a dominant
factor decreased bacterial richness and catabolic diversity due to abated enzymes
activities in correlation with the process of biodegradation. Dispersants exerted
no negative consequences on microbial composition, however, bacterial composition
by the Chloroflexi, TM6, OP8, Cyanobacteria and Gemmatimonadetes phyla increased.
It seemed that more frequent fertilizer application could be equally safe to
bacteria and increased significantly the abundance of bacterial strains but
Actinobacteria phyla decreased.
PMID- 27485783
TI - Impact on water surface due to deepwater gas blowouts.
AB - This paper presents a study on the impact of underwater gas blowouts near the
ocean surface, which has a greater relevance to assess Health, Safety, and
Environmental risks. In this analysis the gas flux near the surface, reduction of
bulk density, and gas surfacing area are studied for different scenarios. The
simulations include a matrix of scenarios for different release depths, release
rates, and initial bubble size distributions. The simulations are carried out
using the MEGADEEP model, for a location in East China Sea. Significant changes
in bulk density and gas surface flux near the surface are observed under
different release conditions, which can pose a potential threat for cleanup and
rescue operations. Furthermore, the effect of hydrate formation on gas surfacing
is studied for much greater release depths. The type of outcomes of this study is
important to conduct prior risk assessments and contingency planning for
underwater gas blowouts.
PMID- 27485784
TI - Viral hepatitis: The global burden of viral hepatitis is increasing.
PMID- 27485785
TI - Viral hepatitis: beginning of the end?
PMID- 27485787
TI - Obesity: Childhood obesity: time bomb for future burden of chronic liver disease.
PMID- 27485788
TI - Gut microbiota: Microbiota and behaviour: visiting the sins of the mother.
PMID- 27485789
TI - Colorectal cancer: Engineered colons for cancer research.
PMID- 27485786
TI - Adult and paediatric GERD: diagnosis, phenotypes and avoidance of excess
treatments.
AB - Detailed investigations and objective measurements in patients with symptoms of
gastro-oesophageal reflux should be performed with the intent of making the
correct diagnosis, thus enabling choice of appropriate therapy. Establishing the
most effective therapy is particularly important in adults who do not respond to
standard treatment and in children. The use of PPIs for suspected GERD has
increased substantially over the past decade, providing great relief in patients
with acid-related symptoms, but also leading to adverse effects and a
considerable economic burden. Adults with functional heartburn do not benefit
from PPIs, while prolonged PPI use in patients with extraoesophageal symptoms
remains a controversial area. Moreover, PPIs are not indicated in infants with
GERD unless symptoms are proven to be acid-related. With regard to antireflux
surgery, patients must be carefully selected to avoid the need for ongoing PPI
treatment postoperatively. Correct diagnosis and phenotyping of patients with
symptoms attributed to gastro-oesophageal reflux through detailed investigations
is therefore imperative, leading to improved patient outcomes and rationalized
use of available treatment options. In this Review, we outline currently
available diagnostic tests and discuss approaches to limit any unnecessary
medical or surgical interventions.
PMID- 27485790
TI - Immunology: A glia-ILC3 axis.
PMID- 27485791
TI - Downregulation of thrombospondin-1 by DNA hypermethylation is associated with
tumor progression in laryngeal squamous cell carcinoma.
AB - Thrombospondin-1 (THBS-1) has been demonstrated to have a complicated role in
human cancer and to exert stimulatory and inhibitory effects in different types
of tumors. DNA methylation, as the most frequent mechanism for gene silencing,
has been widely investigated in regards to the development of tumors. However,
the expression levels and methylation status of THBS-1, and their roles in
laryngeal squamous cell carcinoma (LSCC) remain to be elucidated. The present
study detected downregulated THBS-1 mRNA and protein expression levels in LSCC by
using reverse transcription-quantitative polymerase chain reaction (PCR) and
western blotting, while decreased expression levels of THBS-1 mRNA and protein
were significantly associated with lymph node metastasis and tumor-node
metastasis (TNM) stage. Furthermore, aberrant methylation of THBS-1 was
frequently observed in LSCC by methylation-specific PCR, particularly in tumor
tissues from lymph node metastasis or samples from cancer with advanced TNM
stage. Furthermore, the current study demonstrated that downregulated expression
of THBS-1 in LSCC was consistent with aberrant methylation of this gene.
Treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxy-cytidine in Hep
2 cells induced demethylation of THBS-1, enhanced THBS-1 expression, and
inhibited the proliferative and invasive ability of Hep-2 cells. Collectively,
the results of the present study suggest that THBS-1 may exert an inhibitory
effect in the development of LSCC. Aberrant methylation was an important reason
for the downregulation of THBS-1 and was involved in the invasion and metastasis
of LSCC. Demethylating agents may be effective candidates for the treatment of
LSCC.
PMID- 27485792
TI - Primary cilium and autophagy: The avengers of cell-size regulation.
AB - The maintenance of cellular homeostasis in response to extracellular stresses by
autophagy is vital for the health of various tissues. Extracellular stimuli may
include nutrient starvation, endoplasmic reticulum stress, hypoxia, cytotoxic
agents, or mechanical stress. The primary cilium (PC) is a microtubule-based
sensory organelle that regulates the integration of various extracellular
stimuli. The interconnection between macroautophagy/autophagy and the PC is
beginning to be illuminated. In this punctum, we discuss our recent study of PC
dependent autophagy in response to fluid flow in kidney epithelial cells. Urinary
flow in kidney tubules creates a shear stress that regulates epithelial cell
volume. PC-mediated autophagy is necessary for the regulation of cell size. The
signal from the PC is transduced by the activation of STK11/LKB1 and by MTOR
inhibition. Our results clarify the physiological role of PC-dependent autophagy
in the kidney and suggest that autophagy manipulation may provide a route to the
treatment of ciliopathies.
PMID- 27485793
TI - Epileptic phenotype of FGFR3-related bilateral medial temporal lobe dysgenesis.
AB - Hypochondroplasia (HCH) is a skeletal dysplasia, characterized by short stature
and macrocephaly. Clinical symptoms and radiological and histopathological
features of HCH are similar, but milder than those seen in achondroplasia.
Particularly, HCH patients with Asn540Lys mutation in the FGFR3 gene are reported
to have medial temporal lobe dysgenesis and epilepsy. We report a 3-year-old girl
who developed recurrent epileptic apnea, which started immediately after birth.
The apneic seizures were refractory to antiepileptic medications; ictal
electroencephalography showed rhythmic activity originating from the left or
right temporal areas and rarely from the right frontal area. Macrocephaly was
noted since birth. Neuroimaging revealed bilateral dysgenesis and hypometabolism
of the medial temporal structures as well as perfusion changes in the left
lateral temporofrontal areas during the ictal period. Clonazepam was initiated
and acetazolamide dosage was increased at 6months, resulting in complete seizure
control after 8months of age. Genetic analysis identified an Asn540Lys (c.1620
C>A) mutation in the FGFR3 gene. Characteristic bone findings on the lumbar
spine, iliac bone, and femur were retrospectively confirmed on X-rays during
infancy. This was the first report that delineated the epilepsy phenotype in
FGFR3-related bilateral medial temporal lobe dysgenesis; such findings would lead
to an early diagnosis and better epilepsy management.
PMID- 27485795
TI - Abstracts from EMCON 2014: International Conference on Emergency Medicine; 16th
Annual Conference by the Society for Emergency Medicine in India (SEMI).
PMID- 27485794
TI - Polyphenol, antioxidant and antimicrobial potential of six different white and
red wine grape processing leftovers.
AB - BACKGROUND: During winemaking, grape polyphenols are only partly extracted, and
consequently unexploited. The main aim was to characterize the phenolic content
of freeze-dried grape skin and seed (FDSS) extracts obtained from Slovenian and
international grape varieties and to evaluate their antioxidant, antimicrobial
and anti-adhesive activities. RESULTS: FDSS of six Vitis vinifera L. grapevine
cultivars from Vipava Valley region (Slovenia) underwent extraction and
sonification under different conditions. Flavonols were the predominant content
of extracts from white 'Zelen' and 'Sauvignon Blanc' grape varieties, with strong
antimicrobial activities against Gram-negative bacteria. 'Pinot Noir' FDSS
extracted with 50% aqueous ethanol extraction produced a high phenolic content in
the final extract, which was further associated with strong antioxidant and
antimicrobial activities against all tested bacteria. Bacterial adhesion to
stainless steel surfaces with minimal and maximal surface roughness was
significantly inhibited (up to 60%) across a wide FDSS concentration range, with
lower concentrations also effective with two types of stainless steel surfaces.
CONCLUSION: FDSS extracts from winery by-products show interesting phenolic
profiles that include flavonols, catechins, anthocyanins and hydroxycinnamic
acids, with yields influenced by grapevine cultivar and extraction conditions.
The antioxidant, antimicrobial and anti-adhesive activities of 50% aqueous
ethanol 'Pinot Noir' FDSS extract reveals potential applications in food,
pharmaceutical and cosmetic industries for these bioactive residues. (c) 2016
Society of Chemical Industry.
PMID- 27485797
TI - A two-component nonphotochemical fluorescence quenching in eustigmatophyte algae.
AB - Eustigmatophyte algae represent an interesting model system for the study of the
regulation of the excitation energy flow due to their use of violaxanthin both as
a major light-harvesting pigment and as the basis of xanthophyll cycle.
Fluorescence induction kinetics was studied in an oleaginous marine alga
Nannochloropsis oceanica. Nonphotochemical fluorescence quenching was analyzed in
detail with respect to the state of the cellular xanthophyll pool. Two components
of nonphotochemical fluorescence quenching (NPQ), both dependent on the presence
of zeaxanthin, were clearly resolved, denoted as slow and fast NPQ based on
kinetics of their formation. The slow component was shown to be in direct
proportion to the amount of zeaxanthin, while the fast NPQ component was
transiently induced in the presence of membrane potential on subsecond
timescales. The applicability of these observations to other eustigmatophyte
species is demonstrated by measurements of other representatives of this algal
group, both marine and freshwater.
PMID- 27485796
TI - Sexual transmission-risk behaviour among HIV-positive persons: a multisite study
using social action theory.
AB - AIM: Sexual risk behaviour was explored and described using Social Action Theory.
BACKGROUND: The sexual transmission of HIV is complex and multi-factorial. Social
Action Theory provides a framework for viewing self-regulation of modifiable
behaviour such as condom use. Condom use is viewed within the context of social
interaction and interdependence. DESIGN: Cross-sectional survey. METHODS: Self
report questionnaire administered to adults living with HIV/AIDS, recruited from
clinics, service organizations and by active outreach, between 2010 - 2011.
FINDINGS: Having multiple sex partners with inconsistent condom use during a 3
month recall period was associated with being male, younger age, having more
years of education,substance use frequency and men having sex with men being a
mode of acquiring HIV. In addition, lower self-efficacy for condom use scores
were associated with having multiple sex partners and inconsistent condom use.
CONCLUSION: Social Action Theory provided a framework for organizing data from an
international sample of seropositive persons. Interventions for sexually active,
younger, HIV positive men who have sex with men, that strengthen perceived
efficacy for condom use, and reduce the frequency of substance use, may
contribute to reducing HIV-transmission risk.
PMID- 27485798
TI - Relationship between physico-chemical characteristics and potential toxicity of
PM10.
AB - PM10 was sampled at a suburban location affected by traffic and industry in the
north of Spain. The samples were analysed to determine the chemical components of
PM10 (organic and elemental carbon, soluble chemical species and metals). The aim
of this study was to assess the toxicity of PM10 in terms of the bulk analysis
and the physico-chemical properties of the particles. Total carbon, sulphates,
ammonium, chlorides and nitrates were found to be the major constituents of PM10.
The contribution of the last of these was found to increase significantly with
PM10 concentration (Pearson coefficient correlation of 0.7, p-value < 0.001).
Individual airborne particles were characterised morphologically and chemically
via a combination of Scanning Electron Microscopy and Energy-Dispersive X-ray
spectroscopy (SEM-EDX). The subsequent image analysis revealed C-rich particles
with shapes that pointed to combustion processes. Moreover, carbonaceous
particles seemed to act as vehicles for sulphur compounds and metals (S, Na, Fe,
Ca, Mg, K, Al, Mn, Zn and Cu). Coarse particles were found to be mainly
constituted by crustal material and marine and carbonaceous particles. Although
most of the studied individual particles in PM10 samples (86.0%) had a diameter
within the 0.1-2.5 MUm range, 1.8% of them had sizes lower than 0.1 MUm 40.2% of
the total studied particles were estimated to be inhaled and deposited in the
human respiratory tract; 12.3% of these particles would reach the deepest zones,
thereby posing a major risk to human health.
PMID- 27485799
TI - Pollution status of polycyclic aromatic hydrocarbons in surface sediments from
the Yangtze River Estuary and its adjacent coastal zone.
AB - Polycyclic aromatic hydrocarbons (PAHs) are mainly produced by incomplete
combustion and are used as indicators of anthropogenic activities on the
environment. This study analyses the PAHs level in the Yangtze River Estuary
(YRE), an important component of Yangtze River and a developed and populated
region in China. Surface sediments were collected from 77 sites at the YRE and
its adjacent coastal zone (IACZ) for a comprehensive study of PAHs. Kriging
interpolation technology and Positive matrix factorization (PMF) model were
applied to explore the spatial distribution and sources of PAHs. Concentrations
of 16 PAHs (SigmaPAHs) varied from 27.2 ng g(-1) to 621.6 ng g(-1) dry weight,
with an average value of 158.2 ng g(-1). Spatially, SigmaPAHs exhibited wide
fluctuation and exhibited an increasing tendency from north to south. In
addition, SigmaPAHs exhibited a decreasing trend with increasing distance between
the estuary and IACZ. The deposition flux of PAHs indicated that more than 107.8
t a(-1) PAHs was deposited in the study area annually. The results of the PMF
model revealed that anthropogenic activities were the main sources of PAHs in the
study area. Vehicle emissions and marine engines were the most important sources
and accounted for 40.9% of the pollution. Coal combustion, petrogenic sources,
and wood combustion were other sources that contributed 23.9%, 23.6%, and 11.5%,
respectively. The distribution patterns of PAHs in the YRE and IACZ were
influenced by many complicated factors such as sediment grain size, hydrodynamics
and so on.
PMID- 27485800
TI - News from the editors of Neurogastroenterology and Motility.
PMID- 27485801
TI - Functional and genetic characterization of hydrocarbon biodegrader and exopolymer
producing clones from a petroleum reservoir metagenomic library.
AB - Microbial degradation of petroleum is a worldwide issue, which causes physico
chemical changes in its compounds, diminishing its commercial value.
Biosurfactants are chemically diverse molecules that can be produced by several
microorganisms and can enable microbial access to hydrocarbons. In order to
investigate both microbial activities, function-driven screening assays for
biosurfactant production and hydrocarbon biodegradation were carried out from a
metagenomic fosmid library. It was constructed from the total DNA extracted from
aerobic and anaerobic enrichments from a Brazilian biodegraded petroleum sample.
A sum of 10 clones were selected in order to evaluate their ability to produce
exopolymers (EPS) with emulsifying activity, as well as to characterize the gene
sequences, harbored by the fosmid clones, through 454 pyrosequencing. Functional
analyses confirmed the ability of some clones to produce surfactant compounds.
Regarding hydrocarbon as microbial carbon sources, n-alkane (in mixture or not)
and naphthalene were preferentially consumed as substrates. Analysis of sequence
data set revealed the presence of genes related to xenobiotics biodegradation and
carbohydrate metabolism. These data were corroborated by the results of
hydrocarbon biodegradation and biosurfactant production detected in the evaluated
clones.
PMID- 27485802
TI - Perioperative non-invasive haemodynamic monitoring: Yes or not yet?
PMID- 27485803
TI - The efficacy of intra-articular lidocaine administration in chronic knee pain due
to osteoarthritis: A randomized, double-blind, controlled study.
AB - BACKGROUND: Intra-articular injections for the treatment of knee pain due to
osteoarthritis are performed when conservative therapies have failed. The intra
articular injection of lidocaine may be an effective treatment modality due to
its neuronal membrane-stabilizing effect and long-lasting anti-inflammatory
action. In this study, we compared the efficacy of intra-articular 0.5% lidocaine
versus saline injection on pain, stiffness and physical function in patients with
osteoarthritis. METHODS: Patients with osteoarthritis were randomly allocated to
two groups. Group I (n=26) received 7mL 0.5% lidocaine and group II (n=26)
received 7mL saline into the painful knee for a series of three injections spaced
by 1 week intervals under ultrasound guidance. Knee pain was measured with a
numeric rating score (NRS) at baseline and 3 months after the 3rd injection.
WOMAC scales, including pain (WOMAC-P), stiffness (WOMAC-S) and physical function
(WOMAC-F), were assessed and recorded at baseline, 30minutes after the 1st
injection, immediately prior to the 2nd and 3rd injections and 3 months after the
3rd injection. RESULTS: Demographic data were comparable between groups. The NRS
after 3 months was significantly lower in group I (P=0.001). The WOMAC-P,
immediately prior to the 3rd injection and 3 months afterwards, was significantly
lower in group I (P=0.006, P=0.001, respectively). The WOMAC-S was improved prior
to the 3rd injection and sustained until 3 months in group I (P=0.035, P=0.004,
respectively). The WOMAC-F was improved after the 1st injection and sustained
until 3 months in group I (P=0.002, P<0.0001 and P<0.0001, respectively).
CONCLUSIONS: Intra-articular 0.5% lidocaine injection under ultrasound guidance
has a potential role in the management of chronic knee pain due to osteoarthritis
for a 3-month period.
PMID- 27485804
TI - The risk of atrial fibrillation after pneumonectomy is not impaired by
preoperative administration of dexamethasone. A cohort study.
AB - INTRODUCTION: Atrial fibrillation (AF) is one of the most frequent complications
occurring after thoracic surgery especially after lung resection. It is
associated with an increase in postoperative morbidity and mortality. Recent data
having documented the preventive role of corticosteroids on the occurrence of AF
in cardiac surgery, we sought to evaluate the effect of preoperative
administration of dexamethasone on the incidence of AF after pneumonectomy.
METHODS: We reviewed the files of all consecutive patients who underwent a
pneumonectomy in one single centre between July 2004 and July 2012. For each
patient, demographics, medical status, the surgical procedure and treatments
administered including dexamethasone, were recorded. The data were analysed using
a univariate analysis and a multivariate logistic regression. RESULTS: Among
them, 153 patients were included and analysed; 35 (23%) presented with at least
one episode of AF occurring within 48hours after surgery. Mortality was higher in
these patients (26.5% versus 12.1%, P=0.06). The univariate analysis indicated
that patients who had a postoperative course complicated by the occurrence of AF
were older (P=0.003), had a higher SAPS2 score (P=0.002) and a higher CHADS score
(P=0.05). Older age (OR=1.08; P=0.048) and preoperative treatment by anti
arrhythmics (OR=3.9; P=0.029) were documented as independent risk factors in the
multivariate analysis. Preoperative administration of dexamethasone 8-12mg did
not impair the incidence of AF. DISCUSSION: AF is a frequent complication after
pneumonectomy associated with increased mortality. Whereas corticosteroids have
been documented as preventing AF following cardiac surgery, no such effect was
found after pneumonectomy.
PMID- 27485805
TI - Large vein injection alleviates rocuronium-induced pain in gynaecologic patients.
AB - BACKGROUND: Rocuronium-induced pain upon injection is very common in the clinical
setting. Using the antecubital rather than the hand vein can avoid pain due to
propofol injection. We aimed to investigate whether the use of the antecubital
vein for injection would alleviate rocuronium-induced pain in a similar fashion.
METHODS: Sixty patients (ASA classes I and II) scheduled for gynaecologic
laparoscopy were randomised into two groups. Rocuronium (0.6mg/kg) was injected
either into the vein on the dorsum of the hand (group D) or a large vein in the
antecubital fossa (group A). Pain was assessed and recorded using a four-point
scale. RESULTS: Compared with group D, the incidence of pain and severe pain was
lower in group A patients. The rate of no pain was also higher in group A
patients. CONCLUSION: The incidence and severity of rocuronium-induced injection
pain were significantly alleviated via use of a large vein for rocuronium
injection.
PMID- 27485806
TI - Intrathoracic small bowel obstruction with cardiac compression.
PMID- 27485808
TI - Effect of floorball training on blood lipids, body composition, muscle strength,
and functional capacity of elderly men.
AB - Floorball training consists of intense repeated exercise and may offer a
motivating and social stimulating team activity in elderly individuals. However,
the effect of floorball training in elderly adults on physiological adaptations
important for health is not known. Thus, this study examined the effect of
floorball training on blood lipids, muscle strength, body composition, and
functional capacity of men aged 65-76 years. Thirty-nine recreational active men
were randomized into a floorball group (FG; n = 22) or petanque group (PG; n =
17), in which training was performed 1 h twice a week for 12 weeks. In FG and PG,
average heart rate (HR) during training was 80% and 57%, respectively, of maximal
HR. In FG, plasma low-density lipoprotein (LDL) cholesterol and triglycerides
were 11% and 8% lower (P < 0.05), respectively. Insulin resistance determined by
homeostatic model assessment (HOMA-IR) was reduced (P < 0.05) by 18%. HR during
submaximal cycling was 5% lower (P < 0.05), and maximal voluntary contraction
force was 8% higher (P < 0.05). Total and visceral fat content was lowered (P <
0.05) by 5% and 14%, respectively, HR at rest was 8% lower (P < 0.05) and
performance in four different functional capacity tests were better (P < 0.05)
after compared to before the training period. No changes were observed in PG. In
conclusion, 12 weeks of floorball training resulted in a number of favorable
effects important for health and functional capacity, suggesting that floorball
training can be used as a health-promoting activity in elderly men.
PMID- 27485807
TI - Utilization of different anti-viral mechanisms by mammalian embryonic stem cells
and differentiated cells.
AB - Embryonic stem cells (ESCs) have received tremendous attention because of their
potential applications in regenerative medicine. Over the past two decades,
intensive research has not only led to the generation of various types of cells
from ESCs that can be potentially used for the treatment of human diseases but
also led to the formation of new concepts and breakthroughs that have
significantly impacted our understanding of basic cell biology and developmental
biology. Recent studies have revealed that ESCs and other types of pluripotent
cells do not have a functional interferon (IFN)-based anti-viral mechanism,
challenging the idea that the IFN system is developed as the central component of
anti-viral innate immunity in all types of cells in vertebrates. This finding
also provided important insight into a question that has been uncertain for a
long time: whether or not the RNA interference (RNAi) anti-viral mechanism
operates in mammalian cells. An emerging paradigm is that mammals may have
adapted distinct anti-viral mechanisms at different stages of organismal
development; the IFN-based system is mainly used by differentiated somatic cells,
while the RNAi anti-viral mechanism may be used in ESCs. This paper discusses the
molecular basis and biological implications for mammals to have different anti
viral mechanisms during development.
PMID- 27485809
TI - Importance of a Fluorine Substituent for the Preparation of meta- and para
Pentafluoro-lambda(6) -sulfanyl-Substituted Pyridines.
AB - Although there are ways to synthesize ortho-pentafluoro-lambda(6) -sulfanyl (SF5
) pyridines, meta- and para-SF5 -substituted pyridines are rare. We disclose
herein a general route for their synthesis. The fundamental synthetic approach is
the same as reported methods for ortho-SF5 -substituted pyridines and SF5
substituted arenes, that is, oxidative chlorotetrafluorination of the
corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF4 Cl
pyridines), followed by chloride/fluoride exchange with fluorides. However, the
trick in this case is the presence on the pyridine ring of at least one fluorine
atom, which is essential for the successful transformation of the disulfides into
m-and p-SF5 -pyridines. After enabling the synthesis of an SF5 -substituted
pyridine, ortho-F groups can be efficiently substituted by C, N, S, and O
nucleophiles through an SN Ar pathway. This methodology provides access to a
variety of previously unavailable SF5 -substituted pyridine building blocks.
PMID- 27485810
TI - Bull's eye and pigment maculopathy are further retinal manifestations of an
abnormal Bruch's membrane in Alport syndrome.
AB - BACKGROUND AND OBJECTIVES: The retinal features of Alport syndrome include a
central and peripheral fleck retinopathy, temporal retinal thinning, and a
macular hole. Here we describe further retinal abnormalities. METHODS: We
identified a case of bull's eye maculopathy 20 years previously in a 68-year-old
female, and reviewed archived retinal images from our cohort of X-linked (28
males, 28 females) or autosomal recessive (n = 13) Alport syndrome. All
individuals had Alport syndrome confirmed on genetic testing or renal biopsy,
were examined by an ophthalmologist, and underwent retinal imaging (KOWA non
mydriatic camera, Japan). RESULTS: The index case had the p.Q379X variant in
COL4A5 and currently had renal impairment, (eGFR = 45 ml/min/1.73 m2), bilateral
hearing loss, and central and peripheral retinopathies. Her maculopathy had
deteriorated, and she had a bilateral central visual field loss. Optical
coherence tomography (Heidelberg Spectralis) demonstrated a disrupted retinal
pigment epithelium and retinal atrophy. We identified a further early bull's eye
maculopathy (1/69, 1.4%) from a female with autosomal recessive disease and
normal renal function. We also noted a subtle pigment maculopathy associated with
an abnormal retinal pigment epithelium in 27 (27/69, 39%) subjects with Alport
syndrome, in both males (8/28, 29%) and females (13/28, 46%) with X-linked
disease, and in autosomal recessive disease (6/13, 38%). CONCLUSIONS: The bull's
eye and pigment maculopathies in Alport syndrome result mainly from the damaged
Bruch's membrane and overlying retinal pigment epithelium. Bull's eye maculopathy
affects vision and patients should undergo regular monitoring for retinal
complications.
PMID- 27485811
TI - In situ microscopy for online monitoring of cell concentration in Pichia pastoris
cultivations.
AB - In situ Microscopy (ISM) is an optical non-invasive technique to monitor cells in
bioprocesses in real-time. Pichia pastoris is one of the most promising protein
expression systems. This yeast combines fast growth on simple media and important
eukaryotic features such as glycosylation. In this work, the ISM technology was
applied to Pichia pastoris cultivations for online monitoring of the cell
concentration during cultivation. Different ISM settings were tested. The
acquired images were analyzed with two image processing algorithms. In seven
cultivations the cell concentration was monitored by the applied algorithms and
offline samples were taken to determine optical density (OD) and dry cell mass
(DCM). Cell concentrations up to 74g/L dry cell mass could be analyzed via the
ISM. Depending on the algorithm and the ISM settings, an accuracy between 0.3 %
and 12 % was achieved. The overall results show that for a robust measurement a
combination of the two described algorithms is required.
PMID- 27485812
TI - Production of a polar fish antimicrobial peptide in Escherichia coli using an ELP
intein tag.
AB - An important aspect related to infectious pathogens is their exceptional
adaptability in developing resistance, which leads to a perpetual challenge in
the discovery of antimicrobial drugs with novel mechanisms of action. Among them,
antimicrobial peptides (AMPs) stand out as promising anti-infective molecules. In
order to overcome the high costs associated with isolation from natural sources
or chemical synthesis of AMPs we propose the expression of Pa-MAP 2, a
polyalanine AMP. Pa-MAP 2 was fused to an ELP-intein tag where the ELP (Elastin
like polypeptide) was used to promote aggregation and fast and cost-effective
isolation after expression, and the intein was used to stimulate a controlled AMP
release. For these, the vector pET21a was used to produce Pa-MAP 2 fused to the N
termini region of a modified Mxe GyrA intein followed by 60 repetitions of ELP.
Purified Pa-MAP 2 showed a MIC of 25MUM against E. coli ATCC 8739. Batch
fermentation demonstrated that Pa-MAP-2 can be produced in both rich and defined
media at yields 50-fold higher than reported for other AMPs produced by the ELP
intein system, and in comparable yields to expression systems with protease or
chemical cleavage.
PMID- 27485813
TI - Characterization of nanobodies binding human fibrinogen selected by E. coli
display.
AB - Abnormal levels of fibrinogen (Fib) in blood plasma are associated with several
pathological conditions and hence methods for its detection in blood and body
fluids are essential. Nanobodies (Nbs) or (VHHs) are single domain antibodies
derived from camelids with excellent biophysical and antigen-binding properties,
showing great promise in diagnostics and therapy. In this work, we select and
characterize high affinity Nbs binding human Fib employing an E. coli cell
surface display system based on the fusion of an immune library of VHH domains
with the beta-domain of Intimin. Bacteria displaying high-affinity Nbs against
Fib were selected using magnetic cell sorting (MACS). Specific binding of the
selected clones to Fib was confirmed by flow cytometry of E. coli bacteria, as
well as by enzyme-linked immunosorbent assay (ELISA) and surface plasmon
resonance (SPR) with the purified Nbs. E. coli display also provided an excellent
estimation of the affinity of the selected Nbs by flow cytometry analysis under
equilibrium conditions, with equilibrium constant (KD) values very similar to
those obtained by SPR analysis. Finally, pairwise epitope-scouting studies
revealed that the selected Nbs bound distinct epitopes on Fib. The selected Nbs
are promising diagnostic tools for determination of human Fib levels.
PMID- 27485815
TI - Editorial.
PMID- 27485814
TI - Biosorption of aluminum through the use of non-viable biomass of Pseudomonas
putida.
AB - Living and non-living biomass of Pseudomonas putida A (ATCC 12633) was used as
biosorbent for the removing of Al(3+) from aqueous solutions. The process was
stable with time, efficient at pH 4.3 and between 15 degrees C and 42 degrees C.
Two isotherms models were applied to describe the interaction between the
biosorbent and Al(3+). Non-living biomass of P. putida A (ATCC 12633) was found
to be the most efficient at adsorbing Al(3+) with a maximum sorption capacity of
0.55mg Al(3+)/gr adsorbent and with 36*10(5) binding sites of
Al(3+)/microorganisms. Infrared spectroscopy analysis shows that the biosorbent
present some vibrational band of functional groups that change in presence of
Al(3+): hydroxyl, carboxyl and phosphate. Considering that Al(3+) binds to the
phosphate group of phosphatidylcholine, non-viable biomass of P. putida PB01
(mutant lacking phosphatidylcholine) was used. Aluminum adsorption of the
parental strain was 30 times higher than values registered in P. putida PB01
(36*10(5) sites/microorganism vs 1.2*10(5) sites/microorganism, respectively).
This result evidenced that the absence of phosphatidylcholine significantly
affected the availability of the binding sites and consequently the efficiency of
the biomass to adsorb Al(3+).
PMID- 27485816
TI - In Vitro Metabolism Evaluation of the Ergot Alkaloid Dihydroergotamine:
Application of Microsomal and Biomimetic Oxidative Model.
AB - Dihydroergotamine is a semisynthetic natural product derived from ergotamine, an
ergot alkaloid. It is used to treat migraines, a neurological disease
characterized by recurrent moderate to severe headaches. In this work, the in
vitro metabolism of dihydroergotamine was evaluated in a biomimetic phase I
reaction, aiming to verify all possible formed metabolites. Dihydroergotamine was
submitted to an in vitro metabolism assay using rat liver microsomes, and the
metabolites were analyzed by HPLC-MS/MS. The biomimetic reactions were performed
with Jacobsen catalyst for scaling up production of oxidized metabolites. Two
hydroxylated metabolites were isolated and characterized by MS/MS and 1H NMR
analysis.
PMID- 27485817
TI - Left atrial enlargement is an independent predictor of stroke and systemic
embolism in patients with non-valvular atrial fibrillation.
AB - Controversy exists regarding whether left atrial enlargement (LAE) is a predictor
of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The
Fushimi AF Registry, a community-based prospective survey, enrolled all AF
patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline
echocardiographic data were available for 2,713 patients by August 2015. We
compared backgrounds and incidence of events over a median follow-up of 976.5
days between patients with LAE (left atrial diameter > 45 mm; LAE group) and
those without in the Fushimi AF Registry. The LAE group accounted for 39% (n =
1,049) of cohort. The LAE group was older and had longer AF duration, with more
prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral
anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE
group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval
(CI): 1.40-2.64; p < 0.01; without OAC; HR: 1.97, 95% CI: 1.18-3.25; p < 0.01;
with OAC; HR: 1.83, 95% CI: 1.21-2.82; p < 0.01). LAE was independently
associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25-2.42; p <
0.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In
conclusion, LAE was an independent predictor of stroke/SE in large community
cohort of AF patients.
PMID- 27485818
TI - Mammary epithelial morphogenesis and early breast cancer. Evidence of involvement
of basal components of the RNA Polymerase I transcription machinery.
AB - Upregulation of RNA Polymerase (Pol I)-mediated transcription of rRNA and
increased ribogenesis are hallmarks of breast cancer. According to several
datasets, including The Cancer Genome Atlas (TCGA), amplification/upregulation of
genes encoding for basal components of the Pol I transcriptional machinery is
frequent at different breast cancer stages. Here we show that knock down of the
RNA polymerase I-specific transcription initiation factor RRN3 (TIF-IA) in breast
cancer cells is sufficient to reduce rRNA synthesis and inhibit cell
proliferation, and second that stable ectopic expression of RRN3 in human mammary
epithelial (HME1) cells, by increasing rRNA transcription, confers increased
sensitivity to the anti-proliferative effects of a selective Pol I inhibitor.
Further, RRN3-overexpressing HME1 cells, when grown in in vitro 3-dimensional
(3D) culture, develop into morphologically aberrant acinar structures lacking a
lumen and filled with proliferative cells, thus acquiring a morphology resembling
in situ ductal breast cancer lesions (DCIS). Consequently, interference with RRN3
control of Pol I transcription seems capable of both compromising mammary
epithelial morphogenetic processes at early breast cancer stages, and driving
breast cancer progression by fostering proliferation.
PMID- 27485819
TI - Multifocal Surgically Induced Necrotizing Scleritis Following Strabismus Surgery:
A Case Report.
AB - PURPOSE: To present clinical findings of a 28-year-old woman with multifocal
surgically induced necrotizing scleritis following uncomplicated strabismus
surgery. METHOD: A 28-year-old woman underwent uncomplicated strabismus surgery
of her right eye for sensory exotropia under general anesthesia (6 mm right
medial rectus muscle resection and 8 mm right lateral rectus muscle recession).
DESIGN: Retrospective, observational case report and literature review. RESULTS:
One month after strabismus surgery, the patient presented with surgically induced
necrotizing scleritis in the nasal aspect of sclera. Bacterial culture of the bed
of the scleral melt showed no growth and all laboratory evaluation was normal.
The scleritis completely resolved after initiation of systemic corticosteroids
and oral azathioprine. Three weeks later (after tapering dose of systemic
medication), the patient returned with large area of necrotizing scleritis in the
same eye, but this time in the temporal aspect of sclera. CONCLUSION: To our
knowledge, this is the first documented case of multifocal surgically induced
necrotizing scleritis occurring after strabismus surgery. This study also
highlights the fact that scleritis may recur even in an area distant from the
site of surgery, despite initial control. It seems that maybe with a longer
course of treatment it is less likely to recur, and tapering medications should
be carefully managed.
PMID- 27485820
TI - PPARalpha-ATGL pathway improves muscle mitochondrial metabolism: implication in
aging.
AB - Adipose triglyceride lipase (ATGL) maintains an optimum mitochondrial function
putatively by generating cognate ligands for peroxisome proliferator-activated
receptor alpha (PPARalpha), which, together with PPARgamma coactivator-1alpha
(PGC1alpha), regulate muscle mitochondrial biogenesis. However, the cross-talk
between ATGL and PPARalpha in skeletal muscle mitochondrial metabolism and its
implication in chronological aging is poorly understood. The role of ATGL in
muscle mitochondrial metabolism was studied by overexpressing and depleting the
gene and studying its downstream effect in cultured myotubes and in murine
skeletal muscle. We found that PPARalpha directly induces ATGL expression during
myogenesis. Overexpression of ATGL significantly enhanced while depletion of ATGL
attenuated mitochondrial oxidative phosphorylation and fatty acid oxidation
without alteration in mitochondrial content, and it rendered PPARalpha and
PGC1alpha redundant in promoting mitochondrial oxidative function. However, ATGL
did not alter PPARalpha-dependent lipid accumulation and insulin sensitivity. In
middle-aged rats, ATGL expression was higher and correlated with PPARalpha
expression and sustained fatty acid oxidation in oxidative soleus muscle.
Fenofibrate feeding further induced ATGL expression selectively in this muscle
compartment. These findings illustrate that PPARalpha and ATGL constitute a
regulatory pathway in skeletal muscle, suggesting their role as a mitochondrial
metabolic reserve.-Biswas, D., Ghosh, M., Kumar, S., Chakrabarti, P. PPARalpha
ATGL pathway improves muscle mitochondrial metabolism: implication in aging.
PMID- 27485821
TI - Maternal serum ADAMTS-9 levels in gestational diabetes: a pilot study.
AB - OBJECTIVE: Gestational diabetes mellitus (GDM) is characterized with insulin
resistance which is diagnosed during pregnancy. Although pregnancy is a
diabetogenic state, not all women develop GDM. Genetic factors together with
enviromental factors cause the maladaptation of maternal pancreas to this
diabetogenic state and GDM develops. ADAMTS-9 is a recently recognized molecule
whose genetic variants have risk of GDM. Decreased levels have already been shown
in fetal membranes. Maternal serum levels of this protein have not been studied
yet. We hypothesized that the alteration of ADAMTS-9 expression should cause
changes in maternal serum levels which further could help to identify the disease
and develop new treatment strategies. MATERIALS AND METHODS: This prospective
case-control study is consisted of 27 pregnancies with GDM and 30 healthy
singleton pregnancies matched for matenal age, gestational week, and maternal
weight. GDM diagnosis was made with 2-h 75 g oral glucose tolerance test. ADAMTS
9 levels were compared between groups. RESULTS: ADAMTS levels were 3.62 +/- 0.33
ng/dL (range: 3.04-4.23) in GDM group and 4.65 +/- 1.70 ng/dL (range: 3.07-8.21)
in control group (p < 0.001). ADAMTS levels were not affected by maternal age,
gestational age, and maternal weight. CONCLUSION: ADAMTS-9 levels were
significantly lower in GDM pregnancies. This may help to understand the mechanism
of GDM pathogenesis. In future, target treatments with ADAMTS proteins may help
to improve the severity of diabetes pathogenesis.
PMID- 27485822
TI - The Empowering Role of Mobile Apps in Behavior Change Interventions: The Gray
Matters Randomized Controlled Trial.
AB - BACKGROUND: Health education and behavior change programs targeting specific risk
factors have demonstrated their effectiveness in reducing the development of
future diseases. Alzheimer disease (AD) shares many of the same risk factors,
most of which can be addressed via behavior change. It is therefore theorized
that a behavior change intervention targeting these risk factors would likely
result in favorable rates of AD prevention. OBJECTIVE: The objective of this
study was to reduce the future risk of developing AD, while in the short term
promoting vascular health, through behavior change. METHODS: The study was an
interventional randomized controlled trial consisting of subjects who were
randomly assigned into either treatment (n=102) or control group (n=42). Outcome
measures included various blood-based biomarkers, anthropometric measures, and
behaviors related to AD risk. The treatment group was provided with a bespoke
"Gray Matters" mobile phone app designed to encourage and facilitate behavior
change. The app presented evidence-based educational material relating to AD risk
and prevention strategies, facilitated self-reporting of behaviors across 6
behavioral domains, and presented feedback on the user's performance, calculated
from reported behaviors against recommended guidelines. RESULTS: This paper
explores the rationale for a mobile phone-led intervention and details the app's
effect on behavior change and subsequent clinical outcomes. Via the app, the
average participant submitted 7.3 (SD 3.2) behavioral logs/day (n=122,719).
Analysis of these logs against primary outcome measures revealed that
participants who improved their high-density lipoprotein cholesterol levels
during the study duration answered a statistically significant higher number of
questions per day (mean 8.30, SD 2.29) than those with no improvement (mean 6.52,
SD 3.612), t97.74=-3.051, P=.003. Participants who decreased their body mass
index (BMI) performed significantly better in attaining their recommended daily
goals (mean 56.21 SD 30.4%) than those who increased their BMI (mean 40.12 SD
29.1%), t80 = -2.449, P=.017. In total, 69.2% (n=18) of those who achieved a mean
performance percentage of 60% or higher, across all domains, reduced their BMI
during the study, whereas 60.7% (n=34) who did not, increased their BMI. One-way
analysis of variance of systolic blood pressure category changes showed a
significant correlation between reported efforts to reduce stress and category
change as a whole, P=.035. An exit survey highlighted that respondents (n=83)
reported that the app motivated them to perform physical activity (85.4%) and
make healthier food choices (87.5%). CONCLUSIONS: In this study, the ubiquitous
nature of the mobile phone excelled as a delivery platform for the intervention,
enabling the dissemination of educational intervention material while
simultaneously monitoring and encouraging positive behavior change, resulting in
desirable clinical effects. Sustained effort to maintain the achieved behaviors
is expected to mitigate future AD risk. TRIAL REGISTRATION: ClinicalTrails.gov
NCT02290912; https://clinicaltrials.gov/ct2/show/NCT02290912 (Archived by WebCite
at http://www.webcitation.org/6ictUEwnm).
PMID- 27485823
TI - Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of
Type 1 Diabetes Mellitus.
AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in
combination with insulin to manage type 2 diabetes mellitus, and four agents are
currently approved for this indication: exenatide, liraglutide, dulaglutide, and
albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c
(A1C) reduction, weight loss, potential to reduce insulin doses, and lower
hypoglycemia risk-have made these agents potential treatment options for patients
with type 1 diabetes mellitus (T1DM) as well. These positive effects are due to
glucose-dependent insulin secretion, reduced glucagon secretion, increased
satiety, and delayed gastric emptying. Patients with T1DM are unable to suppress
glucagon during meals, which contributes to postprandial hyperglycemia and may be
improved with GLP-1 therapy. In this review, we evaluated the available
literature on the clinical efficacy and safety of GLP-1 RAs in patients with
T1DM. We conducted a search of the PubMed (1966-May 2016) and Ovid (1946-May
2016) databases. Abstracts presented at the scientific and clinical sessions of
the American Diabetes Association and the American Association of Clinical
Endocrinologists were also searched. The references of the published articles
were also reviewed to identify additional studies appropriate for inclusion. All
identified articles published in English were evaluated. Studies were included if
they evaluated the clinical use or safety of GLP-1 RAs in patients with T1DM.
Twelve studies were included, with four evaluating exenatide, one evaluating
exenatide extended release, and seven evaluating liraglutide. Both exenatide and
liraglutide showed significant reductions in hemoglobin A1C, plasma glucose
concentration, body weight, and insulin doses when administered to patients with
T1DM already receiving insulin therapy, without increasing the occurrence of
hypoglycemia. Adverse effects were mostly gastrointestinal in nature but were
mild and transient. Patients who may benefit most are those experiencing adverse
effects from insulin, those not at their A1C goal but hypoglycemia prevents
insulin titration, and those who may benefit from weight loss.
PMID- 27485824
TI - Ophthalmic artery Doppler analysis: a window into the cerebrovasculature of women
with pre-eclampsia.
PMID- 27485825
TI - Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of
clear cell renal cell carcinoma.
AB - The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is
frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC),
and therefore these tumors are highly resistant to chemotherapeutic agents,
including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53
(TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is
frequently functional, yet the tumors remain highly insensitive to chemotherapy.
This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC.
The present study aimed to detect the chemosensitivity of CCRCC. The expression
of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a
knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm
that VHL and P53 are both required for chemosensitivity, VHL and P53 were co
expressed in 786-O cells. The results of the functional antagonist assay (which
assessed the IC50 values, i.e. the half maximal inhibitory concentration)
confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle
arrest was measured by propidium iodide staining following treatment with ADM or
sunitinib. Further analysis indicated that co-expression of VHL and P53 inhibited
cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase,
and promoted apoptosis following treatment with ADM or sunitinib. These findings
demonstrated that VHL and P53 act synergistically in the regulation of cell
proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles
in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the
regulatory role of VHL is dependant on the activation P53.
PMID- 27485826
TI - Genome-wide association study of aggressive behaviour in chicken.
AB - In the poultry industry, aggressive behaviour is a large animal welfare issue all
over the world. To date, little is known about the underlying genetics of the
aggressive behaviour. Here, we performed a genome-wide association study (GWAS)
to explore the genetic mechanism associated with aggressive behaviour in
chickens. The GWAS results showed that a total of 33 SNPs were associated with
aggressive behaviour traits (P < 4.6E-6). rs312463697 on chromosome 4 was
significantly associated with aggression (P = 2.10905E-07), and it was in the
intron region of the sortilin-related VPS10 domain containing receptor 2 (SORCS2)
gene. In addition, biological function analysis of the nearest 26 genes around
the significant SNPs was performed with Ingenuity Pathway Analysis. An
interaction network contained 17 genes was obtained and SORCS2 was involved in
this network, interacted with nerve growth factor (NGF), nerve growth factor
receptor (NGFR), dopa decarboxylase (L-dopa) and dopamine. After knockdown of
SORCS2, the mRNA levels of NGF, L-dopa and dopamine receptor genes DRD1, DRD2,
DRD3 and DRD4 were significantly decreased (P < 0.05). In summary, our data
indicated that SORCS2 might play an important role in chicken aggressive
behaviour through the regulation of dopaminergic pathways and NGF.
PMID- 27485829
TI - Palliative stenting of a jejunal stricture secondary to malignant compression
using single-balloon enteroscopy.
PMID- 27485830
TI - Erratum to: AGE-RAGE interaction in the TGFbeta2-mediated epithelial to
mesenchymal transition of human lens epithelial cells.
PMID- 27485827
TI - miR-146b antagomir-treated human Tregs acquire increased GVHD inhibitory potency.
AB - CD4(+)CD25(+)FoxP3(+) thymic-derived regulatory T cells (tTregs) are
indispensable for maintaining immune system equilibrium. Adoptive transfer of
tTregs is an effective means of suppressing graft-versus-host disease (GVHD) in
murine models and in early human clinical trials. Tumor necrosis factor receptor
associated factor 6 (TRAF6), an ubiquitin-conjugating enzyme that mediates
nuclear factor kappaB (NF-kappaB) activation, plays an essential role in
modulating regulatory T cell survival and function. MicroRNAs (miRNAs) are
noncoding RNAs, which mediate RNA silencing and posttranscriptional gene
repression. By performing comprehensive TaqMan Low Density Array miRNA assays, we
identified 10 miRNAs differentially regulated in human tTreg compared with
control T cells. One candidate, miR-146b, is preferentially and highly expressed
in human naive tTregs compared with naive CD4 T cells. miRNA prediction software
revealed that TRAF6 was the one of the top 10 scored mRNAs involved tTreg
function with the highest probability as a potential miR-146b target. Antagomir
mediated knockdown of miRNA-146b, but not another miRNA-146 family member (miRNA
146a), enhanced TRAF6 expression. TRAF6, in turn, increases NF-kappaB activation,
which is essential for tTreg function as well as Foxp3 protein and antiapoptotic
gene expression, and downregulates proapoptotic gene expression. miR-146b
knockdown increased the nuclear localization and expression of genes regulated by
NF-kappaB, which was associated with enhanced tTreg survival, proliferation, and
suppressive function measured in vitro and in vivo. TRAF6 inhibition had the
opposite effects. We conclude that an miR-146b-TRAF6-NF-kappaB-FoxP3 signaling
pathway restrains regulatory T cell survival, proliferation, and suppressor
function. In vitro exposure of human tTregs to miR-146b antagomirs can be
exploited to improve the clinical efficacy of human adoptive tTreg transfer in a
GVHD setting.
PMID- 27485828
TI - Genome of Rhizobium leucaenae strains CFN 299(T) and CPAO 29.8: searching for
genes related to a successful symbiotic performance under stressful conditions.
AB - BACKGROUND: Common bean (Phaseolus vulgaris L.) is the most important legume
cropped worldwide for food production and its agronomic performance can be
greatly improved if the benefits from symbiotic nitrogen fixation are maximized.
The legume is known for its high promiscuity in nodulating with several Rhizobium
species, but those belonging to the Rhizobium tropici "group" are the most
successful and efficient in fixing nitrogen in tropical acid soils. Rhizobium
leucaenae belongs to this group, which is abundant in the Brazilian "Cerrados"
soils and frequently submitted to several environmental stresses. Here we present
the first high-quality genome drafts of R. leucaenae, including the type strain
CFN 299(T) and the very efficient strain CPAO 29.8. Our main objective was to
identify features that explain the successful capacity of R. leucaenae in
nodulating common bean under stressful environmental conditions. RESULTS: The
genomes of R. leucaenae strains CFN 299(T) and CPAO 29.8 were estimated at 6.7
6.8 Mbp; 7015 and 6899 coding sequences (CDS) were predicted, respectively, 6264
of which are common to both strains. The genomes of both strains present a large
number of CDS that may confer tolerance of high temperatures, acid soils,
salinity and water deficiency. Types I, II, IV-pili, IV and V secretion systems
were present in both strains and might help soil and host colonization as well as
the symbiotic performance under stressful conditions. The symbiotic plasmid of
CPAO 29.8 is highly similar to already described tropici pSyms, including five
copies of nodD and three of nodA genes. R. leucaenae CFN 299(T) is capable of
synthesizing Nod factors in the absence of flavonoids when submitted to osmotic
stress, indicating that under abiotic stress the regulation of nod genes might be
different. CONCLUSION: A detailed study of the genes putatively related to stress
tolerance in R. leucaenae highlighted an intricate pattern comprising a variety
of mechanisms that are probably orchestrated to tolerate the stressful conditions
to which the strains are submitted on a daily basis. The capacity to synthesize
Nod factors under abiotic stress might follow the same regulatory pathways as in
CIAT 899(T) and may help both to improve bacterial survival and to expand host
range to guarantee the perpetuation of the symbiosis.
PMID- 27485831
TI - Cross-validation of cultural tightness and looseness measures.
AB - The goal of the present study was to cross-validate two measures of cultural
tightness and looseness, CTL: one used in a comparison within the United States,
and the other used in a cross-country comparison. The former was based mainly on
aggregation of state laws on controversial issues and religiosity and the latter
on assessment of homogeneity in moral values among representative samples across
countries. To cross-validate these two measures, both were recomputed at the US
divisional level. Despite the differences in their methods of computation, the
two measures of CTL correlated highly with each other, r = .92, and with
theoretical variables of interest. Further, when the two measures of CTL were
used simultaneously to predict theoretical variables of interest, neither
remained significant suggesting that they were substitutable with each other.
Convergence of results with measures computed via maximally different methods
increases the confidence in the validity of these two CTL measures.
PMID- 27485832
TI - What is the appropriate therapy for asymptomatic gonorrhoea in men who have sex
with men?
PMID- 27485834
TI - [Not Available].
PMID- 27485833
TI - Bipartite graph analyses reveal interdomain LGT involving ultrasmall prokaryotes
and their divergent, membrane-related proteins.
AB - Based on their small size and genomic properties, ultrasmall prokaryotic groups
like the Candidate Phyla Radiation have been proposed as possible symbionts
dependent on other bacteria or archaea. In this study, we use a bipartite graph
analysis to examine patterns of sequence similarity between draft and complete
genomes from ultrasmall bacteria and other complete prokaryotic genomes,
assessing whether the former group might engage in significant gene transfer (or
even endosymbioses) with other community members. Our results provide preliminary
evidence for many lateral gene transfers with other prokaryotes, including
members of the archaea, and report the presence of divergent, membrane-associated
proteins among these ultrasmall taxa. In particular, these divergent genes were
found in TM6 relatives of the intracellular parasite Babela massiliensis.
PMID- 27485835
TI - Telocytes as potential targets in a cyclophosphamide-induced animal model of
premature ovarian failure.
AB - Premature ovarian failure (POF) refers to the presence of ovarian atrophic
permanent amenorrhea in women under the age of 40. The pathogenesis of POF
remains to be fully elucidated. Telocytes are a group of specialized cells with a
small cell volume and very long cytoplasmic prolongations with dichotomous
branching. Previous studies have indicated that telocytes function to support the
trachea and serve as stem cell niches. Although it has been confirmed that
telocytes are present in numerous organs in mammals, it remains to be determined
whether they are present in ovarian tissues and whether they are involved in the
development of POF. The present study used a cyclophosphamide-induced mouse model
of POF. Hematoxylin and eosin staining and an enzyme-linked immunosorbent assay
revealed that cyclophosphamide induced edema and apoptosis of ovarian stromal and
granulosa cells and increased atretic follicles. In addition, cyclophosphamide
induced abnormal peripheral blood FSH and E2 levels in mice. Transmission
electron microscopy revealed a small number of telocyte-like cell structures in
the ovarian stroma of wild-type mice. In addition, flow cytometry and
immunohistochemical staining results suggested that the number of cluster of
differentiation (CD)34/platelet-derived growth factor receptor (PDGFR)alpha,
CD34/PDGFRbeta and CD34/vimentin double-positive cells in the ovaries of POF mice
was significantly decreased compared with wild-type mice. In conclusion, mouse
ovarian tissues appear to contain telocytes, and cyclophosphamide treatment
significantly reduced the number of ovarian telocytes. Therefore, telocytes may
serve as a potential novel marker of POF induced by cyclophosphamide.
PMID- 27485836
TI - Laboratory Innovation Towards Quality Program Sustainability.
AB - Laboratory innovation significantly affects program sustainability of HIV
programs in low and middle income countries (LMICs) far beyond its immediate
sphere of impact. Innovation in rapid development of diagnostic technologies,
improved quality management systems, strengthened laboratory management,
affordable external quality assurance and accreditation schemes, and building
local capacity have reduced costs, brought quality improvement to point-of-care
testing, increased access to testing services, reduced treatment and prevention
costs and opened the door to the real possibility of ending the AIDS epidemic.
However, for effectively implemented laboratory innovation to contribute to HIV
quality program sustainability, it must be implemented within the overall context
of the national strategic plan and HIV treatment programs. The high quality of
HIV rapid diagnostic test was a breakthrough that made it possible for more
persons to learn their HIV status, receive counseling, and if infected to receive
treatment. Likewise, the use of dried blood spots made the shipment of samples
easier for the assessment of different variables of HIV infection-molecular
diagnosis, CD4+ cell counts, HIV antibodies, drug resistance surveillance, and
even antiretroviral drug level measurements. Such advancement is critical for to
reaching the UNAIDS target of 90-90-90 and for bringing the AIDS epidemic to an
end, especially in LMICs.
PMID- 27485837
TI - Past and Future Performance: PEPFAR in the Landscape of Foreign Aid for Health.
AB - This review traces the course of the US President's Emergency Plan for AIDS
Relief (PEPFAR) as a foreign aid program. It illustrates how the epidemiologic
and geopolitical environments of the early 2000s influenced PEPFAR's early
directions and contributed to its successes. In addition to scaling up
infrastructure and care delivery platforms, PEPFAR led to large increases in the
number of people receiving antiretroviral therapy and reductions in mortality.
These successes, in turn, have brought its principal challenges-its outsized
budget, narrow focus, and problem of entitlement-into sharp relief. PEPFAR's
recent evolution, then, has been in response to these challenges. This review
suggests that PEPFAR's early formulation as an emergency response relieved it
from a need to articulate clear goals, and that this freedom is now leading to
new challenges as it struggles to identify priorities in the face of expectations
to do more with a flat budget.
PMID- 27485839
TI - The fungal resistome: a risk and an opportunity for the development of novel
antifungal therapies.
AB - The risks for toxicity of novel antifungal compounds, together with the emergence
of resistance, makes the use of inhibitors of resistance, in combination with
antifungal compounds, a suitable strategy for developing novel antifungal
formulations. Among them, inhibitors of efflux pumps are suitable candidates.
Increasing drug influx or interfering with the stress response may also improve
the efficacy of antifungals. Therapies as induction of fungal apoptosis or
immunostimulation are also good strategies for reducing the risks for resistance
and to improve antifungals' efficacy. Understanding the effect of the acquisition
of resistance on the fungal physiology and determining the collateral sensitivity
networks are useful for the development of novel strategies based on combination
of antifungals for improving the efficacy of the therapy.
PMID- 27485838
TI - Use of Non-invasive Testing to Stage Liver Fibrosis in Patients with HIV.
AB - Patients with HIV have a proclivity to develop liver fibrosis, especially when
associated with other conditions such as HCV, HBV, and NAFLD. Identifying HIV
infected patients with significant fibrosis or cirrhosis plays an important role
in clinical and therapeutic decision-making. Liver biopsy is currently considered
as the gold standard for fibrosis assessment but carries many shortcomings (cost,
invasiveness, complications, false negative rate of 20 %). Multiple non-invasive
methods of liver fibrosis assessment have been developed, but not all have been
studied in HIV-infected individuals. Non-invasive liver fibrosis tools include
both serologic-based testing scores (rely on direct and/or indirect markers) such
as APRI, FIB4, FibroTest, FibroSpect II, HepaScore, or imaging-based methods such
as vibration controlled liver elastography. There is validated data to support
the use of non-invasive modalities of fibrosis assessment in HIV-HCV co-infected
individuals for the exclusion of cirrhosis, but may be poorly reliable or not
enough data exists for the assessment of other co-morbid disease processes.
PMID- 27485840
TI - [Percutaneous endoscopic gastrostomy: analysis of practice at the endoscopic
center of tertiary medical care].
AB - INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a minimally invasive
routine procedure used to provide long-term enteral nutrition in selected
patients with impaired oral intake. The knowledge of clinical, technical and
safety features of PEG is an important issue in clinical practice.The aim of this
study was to evaluate the popu-lation of patients selected for PEG insertion,
describe certain aspects of the insertion procedure, assess the service life of
PEG, as well as account for the number of complications and patient mortality in
the six-month period following the procedure. METHODS: We used a retrospective
analysis of data from medical database. The data were collected in a single
endoscopic tertiary-referral center for a period of seven and a half years.
RESULTS: We evaluated 326 PEG insertions performed on 292 patients with a median
age of 63 years (IQR 55-70). Mortality in the six-month period following PEG
insertion was 26 %. Prevailing indications for PEG insertion were oncological (53
%) and neurological (40 %) diseases, with certain fluctuation of these numbers
during the observed period according to changing demands of the two medical
specialties. Local anesthesia alone was applied in 56 % of patients, 38 %
underwent analgosedation and 6 % required general anesthesia. Median duration of
the procedure (from insertion of endoscope to its final extraction) in 68
consecutive procedures was 6 minutes (IQR 5-8). Median interval between PEG
introduction and its first replacement in 21 patients was 22 months (IQR 14-31,
range 4-76). 61 patients underwent PEG extraction during the observed period, 66
% of whom had oncological disease. Periprocedural complications were seen in 5.8
% of patients, of these one patient (0.3 %) suffered a serious complication. The
buried bumper syndrome was observed in four patients (1.2 %), all of whom had
neurological disease. CONCLUSIONS: PEG is a relatively safe procedure and can be
performed in a short time using local anesthesia or analgosedation in a majority
of patients. The population of patients indicated for PEG insertion reflects
primarily the current needs of neurological and oncological departments. Most
patients within the observed group benefit from PEG insertion for more than six
months. KEY WORDS: analgosedation - complications - mortality - percutaneous
endoscopic gastrostomy.
PMID- 27485841
TI - [Diabetic Kidney Disease 3rd stage - laboratory markers of mineral bone
disorder].
AB - BACKGROUND: Diabetes mellitus is the most common cause of end stage kidney
disease in the developed countries. Chronic kidney disease-mineral and bone
disorder (CKD-MBD) develops with deteriorating of the renal functions. Diabetic
patients on hemodialysis are characterized by low bone turnover, higher
prevalence of severe and progressive vascular calcification with increased
cardiovascular morbidity and mortality. The main factor which causes vascular
calcification in patients with diabetic kidney disease (DKD) is poor glycemic
control. The recent trial findings describe an inverse correlation between intact
parathyroid hormone (iPTH) serum levels and glycemic control in a group of
diabetic patients on hemodialysis. AIM: The objective of the proposed project is
to access the difference of the laboratory markers MBD in the group of patients
with 3rd stage DKD depending on glycemic control. We focused on the relationship
between the glycemic compensation of diabetes (HbA1c) and iPTH serum level.
PATIENTS AND METHOD: Ninety one patients with 3rd stage DKD were investigated.
There were 46 women (50.5 %) and 45 men (49.5 %), average age of patients was
71.2 +/- 7.0 years, with creatinine level 128 +/- 30 MUmol/l and estimated
glomerular filtration (eGF, MDRD) 0.82 +/- 0.16 ml/s. There were 60 patients with
better glycemic control of diabetes (HbA1c < 7 %) vs 29 patients with poorly
controlled diabetes (HbA1c > 7 %). MBD markers were compared in both groups.
Patients were further stratified into subgroups based on the serum level of iPTH
(iPTH < 35 pg/ml vs iPTH > 35 pg/ml) and MBD markers compared. Statistical
analysis was performed using and Mann-Whitney test. RESULTS: We have found the
statistical significance in the serum phosphate and proteinuria levels in between
groups with HbA1c < 7 % vs patients with HbA1c > 7 %. Diabetics with better
glycemic control had significant reduction in serum phosphate level (1.14 +/-
0.20 vs 1.23 +/- 0.18 mmol/l, p = 0.038) and in 24 hrs proteinuria level (0.56 +/
1.35 vs 1.30 +/- 1.61 g/day, p = 0.007). In the group of presumed low bone
turnover (iPTH < 35 pg/ml) we have found the trend towards increased serum
calcium level (2.49 +/- 0.12 vs 2.43 +/- 0.10 mmol/l, p = 0.063) and increased
HbA1c value (7.5 +/- 1.8 vs 6.4 +/- 1.6 %, p = 0.023). CONCLUSION: Our results
suggest the closer relationship between glycemic control of diabetes and mineral
bone disorder in earlier stages of DKD. KEY WORDS: diabetes mellitus type 2
(DM2T) - chronic kidney disease (CKD) - mineral and bone disorder (MBD).
PMID- 27485842
TI - [Long-term treatment of venous thromboembolism in patients with cancer].
AB - BACKGROUND: The treatment with low-molecular-weight heparin (LMWH) is recommended
for patients with cancer associated thrombosis (CAT) during the first 6 months;
the initial therapeutic dose can be reduced to 60-75 % after one month. The
therapy should be reevaluated after 6 month and subsequent therapy using LMWH or
warfarin is recommended indefinitely, unless the cancer is resolved or any major
contraindications arise. AIMS: To analyze the usage of various treatment
modalities in CAT patients after the initial 6 month period according to the
course of cancer. PATIENTS AND METHODS: 87 patients with CAT were followed
prospectively during the treatment period. The proportion of patients, in whom
LMWH was replaced by warfarin during the first 6 months and during the entire
follow up, was analyzed in relation to the course of the cancer. The chi2 test
and chi2 test with Yates correction were used for the statistical evaluation.
RESULTS: The median follow-up was 445 days, mean duration of follow up was 743
days. 6 months after the diagnosis of thrombosis 9/30 (31.0 %) patients with
complete remission (CR) of the cancer were treated with warfarin, while only 3/12
(25 %), 0/9 (0 %) and 1/13 (7.7 %) of the patients with partial remission (PR),
stable disease (SD) and progression, respectively, were treated with warfarin.
Patients with CR and PR were more frequently treated with warfarin than patients
with SD or progression (P = 0.02). 13 patients died during the first 6 months,
and 8 patients were followed less than 6 months. During the entire follow up,
25/30 (83.3 %) patients with CR switched to warfarin, while only 5/12 (41.7 %),
1/9 (11.1 %) and 1/13 (7.7 %) patients with PR, SD, and progression,
respectively, were treated with warfarin. The proportion of patients with CR
which switched to warfarin was higher, than the proportion of patients with PR (P
= 0.007), with SD (P = 0.0003), and with progression (P < 0.0001). Median time
from thrombosis onset to the switch from LMWH to warfarin was 219 days in
patients in complete remission after 6 months and was not reached in patients in
PR,SD, and progression. CONCLUSIONS: The course of malignant disease is important
for the choice of appropriate therapy of CAT after the initial period of LMWH
therapy. The patients achieving complete remission are more prone to switch from
LMWH to warfarin. KEY WORDS: cancer - low-molecular-weight-heparin - venous
thromboembolism - warfarin.
PMID- 27485843
TI - [Annual monitoring of side effects of administering sitagliptin in patients with
type 2 diabetes mellitus].
AB - We present the results of an independent, drug company-unsupported follow-up of
patients with type 2 diabetes mellitus (T2DM) treated with the dipeptidyl
peptidase 4 inhibitor sitagliptin. 29 patients (16 men, 13 women) used
sitagliptin 100 mg daily for one year as an add-on to their chronic antidiabetic
therapy. 16 type diabetic patients formed a control group - they used their
chronic antidiabetic therapy without sitagliptin. 10 additional patients (6 men
and 4 women) were enrolled in the study and treated with sitagliptin for one
month. Body weight, BMI, glycaemia, glycated hemoglobin (HbA1c), cholesterolemia,
triacylglycerolemia and serum amylases were determined and abdominal
ultrasonography was performed. Because significant changes in immunological tests
had been found especially after one month of treatment, 10 additional patients (6
men and 4 women) were enrolled in the study and treated with sitagliptin for one
month. Sitagliptin treatment led to a significant body weight loss of 1 kg per
year. In the control group, no significant change was observed. Similar results
were noticed in HbA1c level and fasting glycaemia - mild but statisticaly
significant reduction in the sitagliptin group both after one month and one year
(not in HbA1c), no difference in the control group. There was no change in
cholesterolemia, or in triacylglycerolemia. In 33% of patients in the sitagliptin
group, the level of liver steatosis decreased by ultrasonographic evaluation.
This was not found in any of the patients case in the control group. The serum
amylase levels increased slightly over the upper limit in two sitagliptin treated
patients. In the other sitagliptin treated patients serum amylase remained within
the laboratory limits, but slight, statistically significant elevation of serum
amylases was observed in the intervened group. This result was not found in the
control group. There were not differences in the frequency between occurence of
mild respiratory infections in the sitagliptin and control group. Marginally
significant decrease was observed in the intervened group. KEY WORDS: sitagliptin
- type 2 diabetes mellitus - side effects.
PMID- 27485844
TI - [Acute causes of sudden deaths in patients with severe hypoglycemia].
AB - Hypoglycemia is a serious event, which is associated with the neurological and
cardiovascular events. Hypoglycemia can be also associated with sudden death,
however, the prevalence of these sudden deaths is not exactly known. Hypoglycemia
is associated with the risk of sudden death in patients with type 1. and 2. type
diabetes mellitus and also in critically ill patients. Sudden death can occure
due to cardiovascular, neurological or metabolic disorders associated with
hypoglycemia. The article provides a review of current knowledge about the
prevalence of severe hypoglycemia, the association between hypoglycemia and
sudden deaths and about the causes of sudden death in patients with severe
hypoglycemia. KEY WORDS: hypoglycemia - prevalence of these sudden deaths -
severe hypoglycemia.
PMID- 27485845
TI - [Cardiomyopathy in MR image].
AB - The purpose of this article is to summarize some general information about the
most common types of cardio-myopathies with an emphasis on a use of cardiac
magnetic resonance imaging (CMR) in its diagnosis. Although characteristic CMR
findings of the cardiomyopathy are generally revealed, the establishing of a
clear diagnosis could be difficult. The assessment of structural myocardial
abnormalities allows determination of the degree of changes in the myocardium and
the prognosis of the disease. The wide range of information about the heart
structure and function is feasible to achieve due to advanced techniques of
magnetic resonance imaging and the ima-ging is not limited by acoustic windows as
it is in case of echocardiography. The role of CMR in diagnostics of the
cardiomyopathies tends to be increasingly important, cardiologists increasingly
favour this examination and it is consequently becoming a standard part of a
diagnostic algorithm. KEY WORDS: amyloidosis - cardiac magnetic resonance -
cardiomyopathy - myocardial hypertrophy.
PMID- 27485846
TI - [Komentar ke clanku HOPE-3: Statins Lower CV Events in Intermediate-CHD-Risk
Patients].
AB - The HOPE-3 study focused on identifying the significance of the polypill and mini
polypill in broad clinical practice, including individuals of different gender
without cardiovascular diseases with an intermediate risk of cardiovascular
diseases. The authors were interested in the question whether people from various
antropologhy groups including not only white people but also other antropologhy
groups - the blacks, people of Asian and South American origin and more covering
6 continents, would respond in a similar way. The study mainly examined the
significance of the mini-polypill, comprising the use of antihypertensive
treatment (16 mg candesartan per day + 12.5 mg hydrochlorothiazide), treatment
with statins (10 mg rosuvastatin per day), and their combination. The study
presents a new way forward in the prevention of cardiovascular diseases, but it
also entails some weaknesses which consist in rather rare medical checkups
including laboratory tests. Owing to that the concept of mini-polypill has met
with some reservation. But it also brings with it reduction of healthcare costs.
KEY WORDS: mini-polypill - prevention of cardiovascular diseases - relevance of
statins also to primary prevention.
PMID- 27485847
TI - [microRNA and internal medicine: from pathophysiology to the new diagnostic and
therapeutic procedures].
AB - microRNAs (abbreviated miRNAs or miRs) represents one of the group of so called
small non-coding RNAs which participate in the negative post-transcriptional
regulation of gene expression. According to the base complementarity they target
molecules of messenger RNAs (mRNAs) which results either in translational
blockade or in degradation of target mRNA. One miRNA usually targets more mRNA
and one mRNA is usually targeted by more than one miRNA - complicated and
interconnected regulatory networks are thus created and their disruption leads to
the abnormalities in development or results in the development of diseases.
Within the past two decades, novel mechanisms were described that enable us to
modulate miRNA levels (either causing upregulation or downregulation) - miRNAs
can thus be considered as a novel potential group of therapeutic targets. First
clinical trials using the blockade of liver specific miR-122 showed very
promising results in the treatment of chronic hepatitis C virus infection.
Results of preclinical and animal studies are also promising providing future
rationale for the development of new therapeutics for various internal diseases
including heart failure, bronchial asthma or inflammatory bowel diseases.
Moreover, miRNAs are not only affecting the pathophysiology of internal diseases,
but they can also reflect their presence - there is a group of miRNAs called
extracellular, or circulating miRNAs, i.e. miRNAs that are present in
extracellular space including all known body fluids such as plasma, serum, urine,
saliva or sweat. Circulating miRNAs are stable; their levels are constant among
the individuals of one species, methods determining their levels are reproducible
and last but not least - levels of extracellular miRNAs differ between healthy
and diseased individuals. They are released into the circulation either after the
cell necrosis or by active transport. Except of being potential novel biomarkers,
these miRNAs represent a novel mean of intercellular communication. Their levels
thus reflect not only the organ damage but also the changes of the homeostasis
during various illnesses. The aim of the current study is to provide the first
insight into the miRNA world to clinicians, especially to internal medicine
specialists. Using simple examples from clinical praxis or clinical
pathophysiology, we are trying to present diagnostic and therapeutic potential
that is hidden within these tiny interesting molecules. KEY WORDS: circulating
microRNA - diagnostics - internal diseases - microRNA - therapy.
PMID- 27485848
TI - [Insulin application techniques in adult patients with diabetes].
AB - Treatment of diabetes mellitus with insulin is associated with a large number of
subcutaneous injections. Incorrect insulin application technique can lead to
complications both local (lipohypertrophy, scars) and systemic (high variability
of insulin absorption and action, unexpected hypoglycemia or hyperglycemia,
suboptimal overall glucose control). Regarding insulin application, we need to
pay particular attention to the risk of intramuscular application and consequent
less expectable insulin effect. The risk of accidental intramuscular
administration of insulin is reduced when shorter 4 mm insulin pen needles are
used. Repeated application of insulin in the same locations may cause changes in
the subcutaneous tissue (lipohypertrophy, inflammation). Application sites should
be examined during routine checks at diabetes clinics. Patients should also be
repeatedly advised to rotate the injection sites as a prevention of
lipohypertrophy formation and not to inject any more injections into
pathologically changed subcutaneous tissue. At the same time, patients should be
advised that their total insulin dose may be decreased, and that they are
temporarily at higher risk of hypoglycemia, if they switch injecting from
lipohypertrophy changed tissue into healthy tissue. KEY WORDS: glucose
variability - insulin application - lipohypertrophy - needles.
PMID- 27485849
TI - [Sinus histiocytosis with massive lymphadenopathy: FDG-PET/CT documented partial
remission after treatment with 2-chlorodeoxyadenosine].
AB - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a
very rare disease belonging to a group of histiocytoses (more precisely non
Langerhans cell histiocytoses). Rosai-Dorfman disease is characterised by the
presence of atypical histiocytic cells in the sinuses of lymph nodes or in the
extranodal lymphoid tissue, absorbing lymphocytes and plasma cells. The structure
and function of the absorbed cells is not impaired and they can leave histiocytes
as viable cells. This effect is called emperipolesis, whereas ingestion of cells
with their destruction is called phagocytosis. In our text we describe a patient
with this disease located, characteristically, in supraclavicular lymph nodes,
but also in mediastinal lymph nodes. Along with lymphadenopathy skin alterations
appeared which were both clinically and histologically described as eczema
dermatitis. At the same time as lymphadenopathy also strong headaches started
which the patient had never suffered before. Within the first-line treatment
prednisone was administered, but no effect was achieved. 2-chlorodeoxyadenosine
in 5 mg/m2 s. c. dose was used in the second-line treatment, for 5 successive
days in monthly intervals. There were four cycles of this treatment administered
overall. Therapy was tolerated without any manifestations of toxicity. Already
after the 1st cycle skin alterations as well as headaches entirely disappeared.
To assess the effect of treatment the PET/CT examination with 18F
fluorodeoxyglucose (FDG-PET/CT) was made. After 4 cycles of treatment the
mediastinal lymph nodes diminished to a physiological size and the accumulation
of fluorodeoxyglucose in them was assessed as physiological. Lymphadenopathy in
the neck area also significantly diminished by 50-75 % and the accumulation of
fluorodeoxyglucose was reduced as well, though it did not reach the norm.
Therefore we evaluate the effect of treatment as a partial remission with
complete disappearance of skin alterations and headaches. The cause of the eczema
and headaches has not been clarified, however considering the same time of their
arising and then disappearance after the application of 2-chlorodeoxyadenosine
the causal connection with Rosai-Dorfman disease is likely. KEY WORDS: Castlemans
disease - lenalidomide - Rosai-Dorfman disease - rituximab - sinus
lymphadenopathy with massive lymphadenopathy - thalidomide - 2
chlorodeoxyadenosine.
PMID- 27485850
TI - Synovial incorporation of polyacrylamide hydrogel after injection into normal and
osteoarthritic animal joints.
AB - OBJECTIVE: Polyacrylamide hydrogel (PAAG) is a non-toxic, non-degradable
synthetic product, used for years in the augmentation of soft tissues.
Preliminary results in animals and humans have suggested long-lasting beneficial
effects on symptoms of osteoarthritis (OA). The aim of this histopathological
study was to investigate whether intra-articular injection of PAAG is integrated
into synovial tissue in normal and OA animal joints, and if this integration is
sustained. METHODS: (A) A prospective, controlled, longitudinal study of normal
knee joints injected with PAAG was performed in 10 rabbits, following the animals
up to 1 year, and (B) a post mortem examination was carried out up to 2 years
post-injection on 18 horse joints which had previously been treated with 1-2
injections of 2 ml PAAG for clinically and radiologically diagnosed OA. RESULTS:
Integration of the injected gel was evident at day 10 in the rabbit and by day 14
in the horse, with proliferation and invasion of synovial cells into the gel. By
day 90 in rabbit joints and day 30 in horse joints, the gel had formed a sub
synovial layer, which was traversed by thin strands of connective tissue with
vessels and covered by a synovial lining facing the joint cavity. This
histological appearance persisted up to 2 years post-injection in horse joints.
CONCLUSION: Intra-articular injection of PAAG results in a stable, long-lasting
sub-synovial layer of gel traversed with thin strands of connective tissue.
Further studies to explore potential effects on synovial inflammation and pain
are warranted.
PMID- 27485852
TI - Assessment of response rates and yields for Two opportunistic Tools for Early
detection of Non-diabetic hyperglycaemia and Diabetes (ATTEND). A randomised
controlled trial and cost-effectiveness analysis.
AB - AIMS: To assess the opportunistic use in primary care of a computer risk score
versus a self-assessment risk score for undiagnosed type 2 diabetes. METHODS: We
conducted a randomised controlled trial in 11 primary care practices in the UK.
577 patients aged 40-75years with no current diagnosis of type 2 diabetes were
recruited to a computer based risk score (Leicester Practice Computer Risk Score
(LPCRS)) or a patient self-assessment score (Leicester Self-Assessment Score
(LSAS)). RESULTS: The rate of self-referral blood tests was significantly higher
for the LPCRS compared to the LSAS, 118.98 (95% CI: 102.85, 137.64) per 1000 high
risk patient years of follow-up compared to 92.14 (95% CI: 78.25, 108.49),
p=0.022. Combined rate of diagnosis of type 2 diabetes and those at risk of
developing the disease (i.e. impaired glucose tolerance (IGT) or impaired fasting
glucose (IFG)) was similar between the two arms, 15.12 (95% CI: 9.11, 25.08) per
1000 high-risk patient years for LPCRS compared to 14.72 (95% CI: 9.59, 22.57)
for the LSAS, p=0.699. For the base case scenario the cost per new case of type 2
diabetes diagnosed was lower for the LPCRS compared to the LSAS, L168 (95%
Credible Interval (CrI): 76, 364), and L352 (95% CrI: 109, 1148), respectively.
CONCLUSIONS: Compared to a self-assessment risk score, a computer based risk
score resulted in greater attendance to an initial blood test and is potentially
more cost-effective.
PMID- 27485851
TI - Diabetes mellitus in Zambia and the Western Cape province of South Africa:
Prevalence, risk factors, diagnosis and management.
AB - AIMS: To determine the prevalence of and risk factors for diabetes mellitus and
examine its diagnosis and management in the study communities. METHODS: This is a
population-based cross-sectional study among adults in 24 communities from Zambia
and the Western Cape (WC) province of South Africa. Diabetes is defined as a
random blood glucose concentration (RBG)?11.1mmol/L, or RBG<11.1mmol/L but with a
self-reported prior diabetes diagnosis. For individuals with a prior diagnosis of
diabetes, RBG<7.8mmol/L was considered to be an acceptable level of glycaemia.
RESULTS: Among 45,767 Zambian and 12,496 WC participants the age-standardised
prevalence of diabetes was 3.5% and 7.2% respectively. The highest risk groups
identified were those of older age and those with obesity. Of those identified to
have diabetes, 34.5% in Zambia and 12.7% in WC were previously unaware of their
diagnosis. Among Zambian participants with diabetes, this proportion was lower
among individuals with better education or with higher household socio-economic
position. Of all those with previously diagnosed diabetes, 66.0% in Zambia and
59.4% in WC were not on any diabetes treatment, and 34.4% in Zambia and 32.7% in
WC had a RBG concentration beyond the recommended level, ?7.8mmol/L. CONCLUSIONS:
The diabetes risk factor profile for our study communities is similar to that
seen in high-income populations. A high proportion of individuals with diabetes
are not on diabetes treatment and of those on treatment a high proportion have
high glycaemic concentrations. Such data may assist in healthcare planning to
ensure timely diagnosis and management of diabetes.
PMID- 27485853
TI - Improved diastolic function in type 2 diabetes after a six month liraglutide
treatment.
AB - AIMS: To investigate whether liraglutide improves diastolic function in type 2
diabetes. METHODS: Thirty-seven patients with type 2 diabetes who began
liraglutide therapy between June 2013 and May 2014 were enrolled in this
observational, prospective study. 26 patients received liraglutide therapy for at
least 6months. The remaining 11 patients withdrew from liraglutide therapy during
the first month, were started on other hypoglycaemic therapies and formed the
control group. Anthropometric, metabolic and echocardiographic parameters
including pulsed wave tissue Doppler imaging were evaluated at baseline and at
6months. RESULTS: In the liraglutide group the early diastolic mitral annulus
velocity on the lateral (e-lat) and medial (e-med) sides of the mitral annulus
increased from 9.2+/-3.4 to 11.6+/-4.7cm/s (p<0.001) and from 6.9+/-1.7 to 8.4+/
2.6cm/s (p<0.003), respectively. The ratio of early-to-late velocities on the
lateral and medial sides of the mitral annulus increased from 0.7+/-0.3 to 0.9+/
0.4 (p<0.001) and from 0.5+/-0.1 to 0.6+/-0.1 (p<0.02), respectively. The ratio
of early diastolic mitral inflow velocity to early diastolic myocardial
relaxation velocity decreased from 10.7+/-4.3 to 8.5+/-2.5 (p<0.005). No
improvements in diastolic function was detected in the control group. Glucose
control improved similarly in both groups: HA1bc -1.5% (-17mmol/mol) vs -1.3% (
14mmol/mol), p=0.67. CONCLUSIONS: In patients with type 2 diabetes, 6months
liraglutide treatment was associated with a significant improvement in diastolic
function.
PMID- 27485854
TI - Application of the limited-memory quasi-Newton algorithm for multi-dimensional,
large flip-angle RF pulses at 7T.
AB - OBJECTIVE: Ultrahigh field MRI provides great opportunities for medical
diagnostics and research. However, ultrahigh field MRI also brings challenges,
such as larger magnetic susceptibility induced field changes. Parallel-transmit
radio-frequency pulses can ameliorate these complications while performing
advanced tasks in routine applications. To address one class of such pulses, we
propose an optimal-control algorithm as a tool for designing advanced multi
dimensional, large flip-angle, radio-frequency pulses. We contrast initial
conditions, constraints, and field correction abilities against increasing pulse
trajectory acceleration factors. MATERIALS AND METHODS: On an 8-channel 7T
system, we demonstrate the quasi-Newton algorithm with pulse designs for reduced
field-of-view imaging with an oil phantom and in vivo with scans of the human
brain stem. We used echo-planar imaging with 2D spatial-selective pulses. Pulses
are computed sufficiently rapid for routine applications. RESULTS: Our dataset
was quantitatively analyzed with the conventional mean-square-error metric and
the structural-similarity index from image processing. Analysis of both full and
reduced field-of-view scans benefit from utilizing both complementary measures.
CONCLUSION: We obtained excellent outer-volume suppression with our proposed
method, thus enabling reduced field-of-view imaging using pulse trajectory
acceleration factors up to 4.
PMID- 27485856
TI - Corrigendum.
PMID- 27485855
TI - Rhizophagus irregularis as an elicitor of rosmarinic acid and antioxidant
production by transformed roots of Ocimum basilicum in an in vitro co-culture
system.
AB - Arbuscular mycorrhiza is a symbiotic association formed between plant roots and
soil borne fungi that alter and at times improve the production of secondary
metabolites. Detailed information is available on mycorrhizal development and its
influence on plants grown under various edapho-climatic conditions, however, very
little is known about their influence on transformed roots that are rich reserves
of secondary metabolites. This raises the question of how mycorrhizal
colonization progresses in transformed roots grown in vitro and whether the
mycorrhizal fungus presence influences the production of secondary metabolites.
To fully understand mycorrhizal ontogenesis and its effect on root morphology,
root biomass, total phenolics, rosmarinic acid, caffeic acid and antioxidant
production under in vitro conditions, a co-culture was developed between three
Agrobacterium rhizogenes-derived, elite-transformed root lines of Ocimum
basilicum and Rhizophagus irregularis. We found that mycorrhizal ontogenesis in
transformed roots was similar to mycorrhizal roots obtained from an in planta
system. Mycorrhizal establishment was also found to be transformed root line
specific. Colonization of transformed roots increased the concentration of
rosmarinic acid, caffeic acid and antioxidant production while no effect was
observed on root morphological traits and biomass. Enhancement of total phenolics
and rosmarinic acid in the three mycorrhizal transformed root lines was found to
be transformed root line-specific and age dependent. We reveal the potential of
R. irregularis as a biotic elicitor in vitro and propose its incorporation into
commercial in vitro secondary metabolite production via transformed roots.
PMID- 27485857
TI - Nano-structured interface of graphene and h-BN for sensing applications.
AB - The atomically-precise controlled synthesis of graphene stripes embedded in
hexagonal boron nitride opens up new possibilities for the construction of
nanodevices with applications in sensing. Here, we explore properties related to
the electronic structure and quantum transport of a graphene nanoroad embedded in
hexagonal boron nitride, using a combination of density functional theory and the
non-equilibrium Green's functions method to calculate the electric conductance.
We find that the graphene nanoribbon signature is preserved in the transmission
spectra and that the local current is mainly confined to the graphene domain.
When a properly sized nanopore is created in the graphene part of the system, the
electronic current becomes restricted to a carbon chain running along the border
with hexagonal boron nitride. This circumstance could allow the hypothetical
nanodevice to become highly sensitive to the electronic nature of molecules
passing through the nanopore, thus opening up ways to detect gas molecules, amino
acids, or even DNA sequences based on a measurement of the real-time conductance
modulation in the graphene nanoroad.
PMID- 27485858
TI - Chemical conversion of mouse fibroblasts into functional dopaminergic neurons.
AB - Ectopic expression of lineage-specific transcription factors facilitates the
conversion of mammalian somatic cells into dopaminergic (DA) neurons, which is a
promising strategy for cell therapy of Parkinson's disease (PD). However, this
approach still has some drawbacks limiting its clinical application due to the
potential risks of integrating vectors into the host genome. Therefore, it is
critical to seek a more desired approach to generate DA neurons derived from
mammalian somatic cells. Here, we report that mouse embryonic fibroblasts (MEFs)
can be efficiently converted into DA neurons by using small molecules along with
specific growth factors. These neuron-like cells generate DA neuronal morphology,
and acquire immunocytochemical and calcium imaging special for neuronal
electrophysiological profile. More importantly, these converted cells can secrete
dopamine, indicating that they are functionally similar to DA neurons. Taken
together, our study might provide a promising cell source for treating PD by
using chemical approach without introduction of exogenous transcription factors.
PMID- 27485859
TI - A review on architecture of the gag-pol ribosomal frameshifting RNA in human
immunodeficiency virus: a variability survey of virus genotypes.
AB - Programmed '-1' ribosomal frameshifting is necessary for expressing the pol gene
overlapped from a gag of human immunodeficiency virus. A viral RNA structure that
requires base pairing across the overlapping sequence region suggests a mechanism
of regulating ribosome and helicase traffic during expression. To get precise
roles of an element around the frameshift site, a review on architecture of the
frameshifting RNA is performed in combination of reported information with
augments of a representative set of 19 viral samples. In spite of a different
length for the viral RNAs, a canonical comparison on the element sequence
allocation is performed for viewing variability associations between virus
genotypes. Additionally, recent and historical insights recognized in
frameshifting regulation are looked back as for indel and single nucleotide
polymorphism of RNA. As specially noted, structural changes at a frameshift site,
the spacer sequence, and a three-helix junction element, as well as two Watson
Crick base pairs near a bulge and a C-G pair close a loop, are the most vital
strategies for the virus frameshifting regulations. All of structural changes,
which are dependent upon specific sequence variations, facilitate an elucidation
about the RNA element conformation-dependent mechanism for frameshifting. These
facts on disrupting base pair interactions also allow solving the problem of
competition between ribosome and helicase on a same RNA template, common to
single-stranded RNA viruses. In a broad perspective, each new insight of
frameshifting regulation in the competition systems introduced by the RNA element
construct changes will offer a compelling target for antiviral therapy.
PMID- 27485860
TI - Communication and Exchange of Specialized Health-Related Support Among People
With Experiential Similarity on Facebook.
AB - Social support is an important factor that shapes how people cope with illness,
and health-related communication among peers managing the same illness (network
ties with experiential similarity) offers specialized information, resources, and
emotional support. Facebook has become a ubiquitous part of many Americans'
lives, and may offer a way for patients and caregivers experiencing a similar
illness to exchange specialized health-related support. However, little is known
about the content of communication among people who have coped with the same
illness on personal Facebook pages. We conducted a content analysis of 12 months
of data from 18 publicly available Facebook pages hosted by parents of children
with acute lymphoblastic leukemia, focusing on communication between users who
self-identified as parents of pediatric cancer patients. Support exchanges
between users with experiential similarity contained highly specialized health
related information, including information about health services use, symptom
recognition, compliance, medication use, treatment protocols, and medical
procedures. Parents also exchanged tailored emotional support through comparison,
empathy, encouragement, and hope. Building upon previous research documenting
that social media use can widen and diversify support networks, our findings show
that cancer caregivers access specialized health-related informational and
emotional support through communication with others who have experienced the same
illness on personal Facebook pages. These findings have implications for health
communication practice and offer evidence to tailor M-Health interventions that
leverage existing social media platforms to enhance peer support for patients and
caregivers.
PMID- 27485861
TI - Association Between Nutritional Status, Inflammatory Condition, and Prognostic
Indexes with Postoperative Complications and Clinical Outcome of Patients with
Gastrointestinal Neoplasia.
AB - The aim of this study is to describe and relate nutritional and inflammatory
status and prognostic indexes with postoperative complications and clinical
outcome of patients with gastrointestinal malignancies. Twenty-nine patients were
evaluated; nutritional assessment was carried out by subjective and objective
parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid
glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the
Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were
used; the clinical outcomes considered were hospital discharge and death. A high
Subjective Global Assessment (SGA) score was associated with the occurrence of
postoperative complications: 73% of the patients with postoperative complications
had the highest SGA score, but only 6% of those without postoperative
complications had the highest SGA score (P < 0.001). Greater occurrence of death
was observed in patients with a high SGA score, low serum albumin, increased CRP,
PINI > 1, and Glasgow score 2. There was a positive correlation between weight
loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI
(P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the
assessment of the nutritional status and the use of prognostic indexes are good
tools for predicting postoperative complications and clinical outcome in patients
with gastrointestinal neoplasia.
PMID- 27485863
TI - [A brief introduction to the disease-syndrome names in bamboo slips of Qin
Dynasty].
AB - There are plenty of names of disease-syndrome from the four kinds of unearthed
Qin bamboo slips, namely Fangmatan, Shuihudi, Zhoujiatai, and Liye. Altogether,
these names number to 85. According to statistics, nomenclature of 34 disease
syndromes are derived from the location of the lesion, 8 from symptoms, 1 from
etiology, 12 from location of lesion plus symptom, 3 from location plus etiology,
and 25 are for special diseases. Through comparison of these names, with those
from oracle bones and Han bamboo slips, Prescriptions for Hundred Kinds of
Disease, it is summarized that, as time passes, nomenclature simply named by the
location of the lesion was gradually reduced, and named by etiology and special
diseases gradually increased. To some extent, it reflects the historical process
of knowledge of the disease gradually deepened in ancient times.
PMID- 27485864
TI - [Evolution of the Origin of Herba Schizonepetae].
AB - Herba Schizonepetae was firstly recorded in the Sheng nong ben caojing
(Shennong's Materia Medica) with the title Jiasu. It could be sure that the
original plant of Jiasu is Ocimumbasilicum L. ofLabiatae based on the record of
Jiasu's name, morphology, edible property before the Song Dynasty. Beginning from
the Ben cao tu jing (Illustrated Classic of Materia Medica) in the Song Dynasty,
the source of this drug evolved as SchizonepetatenuisfoliaBriq. ofLabiatae, and
it has been in use until now. Hence, the sources of Jiasu should be both O.
basilicum L. and the co-existence of S. tenuisfolia Briq in the Qing Dynasty. It
is claimed that the hometowns of those herb writers who considered the source
ofOcimumbasilicum L. to be the producing areas of cultivation of the edible
Ocimumbasilicum L. It was found that the source of Jiasu recorded in the Sheng
nong ben cao jing should be O. basilicum L. , hence, it is suggested the title
Jiasu should be recorded for the source of O. basilicum L, and the original plant
of Herba Schizonepetae was Schizonepetatenuisfolia Briq. of Labiatae, and this
medicine should be separately recorded. In fact, Jiasu and Herba Schizonepetae
were two different kinds of medicines.
PMID- 27485862
TI - Fusion to a homo-oligomeric scaffold allows cryo-EM analysis of a small protein.
AB - Recent technical advances have revolutionized the field of cryo-electron
microscopy (cryo-EM). However, most monomeric proteins remain too small (<100
kDa) for cryo-EM analysis. To overcome this limitation, we explored a strategy
whereby a monomeric target protein is genetically fused to a homo-oligomeric
scaffold protein and the junction optimized to allow the target to adopt the
scaffold symmetry, thereby generating a chimeric particle suitable for cryo-EM.
To demonstrate the concept, we fused maltose-binding protein (MBP), a 40 kDa
monomer, to glutamine synthetase, a dodecamer formed by two hexameric rings.
Chimeric constructs with different junction lengths were screened by biophysical
analysis and negative-stain EM. The optimal construct yielded a cryo-EM
reconstruction that revealed the MBP structure at sub-nanometre resolution. These
findings illustrate the feasibility of using homo-oligomeric scaffolds to enable
cryo-EM analysis of monomeric proteins, paving the way for applying this strategy
to challenging structures resistant to crystallographic and NMR analysis.
PMID- 27485865
TI - [A brief history of traditional Chinese medicinal pills].
AB - Traditional Chinese medicine pill, an archaic medicinal preparation form, is a
kind of spherical or spherical-like preparation form produced by medicinal
powders or extracts mixed with appropriate excipient or other accessories. It was
originated in the Pre-Qin Dynasty, developed and enriched from the Han Dynasty to
the Ming and Qing Dynasties. With the improvement of preparing process, honeyed
pill, waxed pill, coating pill and wax-coating pill etc. appeared in succession.
In modern times, with the progress of pharmaceutical machine, the medicinal pill
is innovated constantly, and at present, it becomes the main form of Chinese
patent medicine with batch production.
PMID- 27485866
TI - [Historical textual research on Shan biandou with discussion on the misnaming of
plant title].
AB - The original plants of Shan biandou, first seen in Jiu huang ben cao (Materia
Medica for Relief of Famines), include the plants of Astragalusgenus, such as A.
scaberrimus and/or A. complanatus in the Ming and Qing Dynasties. But Cassia
mimosoides was named as Shan biandou by Japanese scholars in the 19th century.
This mistaken identification and misnaming, still in use today in Chinese and
Japanese circles of botany and materia medica, did cause some confusion. The
merits and demerits of using the plant names in Chinese characters from the
Japanese language by Chinese botanists were analyzed, the disadvantages of which
should be well avoided. Because of the vicissitude in the names of plants and
Chinese herbs, it is necessary to strengthen the study and develop the
significant value of A. complanatus and C. mimosoides in health care so as to
promote its contributions to the cause of TCM.
PMID- 27485867
TI - [Military medical and health care system in the Song Dynasty].
AB - The military medical and health care system in the Song Dynasty manifested as two
aspects, namely disease prevention and medical treatment. Disease prevention
included ensuring food and drink safety, avoiding dangerous stations and enjoying
regular vacations, etc. Medical treatment included sending medical officials to
patrol, stationing military physicians to follow up, applying emergency programs,
establishing military medical and pharmacy centers, dispensing required
medicines, and accommodating and nursing sick and injured personnel, etc.
Meanwhile, the imperial court also supervised the implementation of military
medical mechanism, in order to check the soldiers' foods, check and restrict the
military physicians' responsibilities, etc., which did play a positive role in
protecting soldier's health, guaranteeing the military combat effectiveness, and
maintaining national security.
PMID- 27485868
TI - [Using Guangming (GB37) acupoint to treat eye diseases: from historical suspense
to modern clinical experiments].
AB - Guangming (GB37) gained its name before the writing of Huang di Ming Tang Jing
(The Yellow Emperor's Mingtang Classic), the earliest work of the art of
acupuncture point. However, in acupuncture and moxibustion works before the Song
Dynasty, this acupoint was not used to treat eye diseases. In Dou Hanqing's Zhen
jiu biao you fu (Song to Elucidate Mysteries in Acupuncture Moxibustion),
Guangming was used to treat oculopathy as an alias of Cuanzhu (BL2). Influenced
by this, the alias "Guangming" was mistaken as Guangming (GB37) of the
Gallbladder Meridian in the Bian que shen ying zhen jiu yu long jing (Bian Que
Acupuncture and Moxibustion Jade Dragon Classic) of the Yuan Dynasty, and the
symptom of eye itch was added to the indications of Guangming (GB37). This was
wrongly informed in the later acupuncture and moxibustion works, and the modern
scholars also accepted it and confirmed its effect by the clinical and
experimental research.
PMID- 27485869
TI - [Changes of career of traditional Chinese medicine in Hong Kong Donghua Hospital
in modern times].
AB - Founded in 1872, the Hong Kong Donghua Hospital (Tung Wah Group of Hospitals
later) was the earliest traditional Chinese hospital in modern times, which has
made positive contributions in exploring the shape and structure of TCM hospital
and promoting science of TCM in Hong Kong. Unfortunately, TCM didn't acquire a
legal status in Hong Kong, the practice of TCM in Donghua Hospital was thus
restricted by the government, and ultimately, it changed into a comprehensive
hospital mainly use western medicine. The change of TCM business in Hong Kong
Donghua Hospital reflected the problems and situation of traditional Chinese
medicine encountered in modern times.
PMID- 27485870
TI - [Health Station, a product of combining the ideas of public health with the
modern Chinese national conditions].
AB - The Health Station was a local health organization founded by the pioneers of the
public health in modern China under the national conditions of "poverty,
ignorance, illness and selfishness" , being the result of combining the ideas of
public health with the Chinese national conditions of modern times. Though this
organization appeared in backward modern China, it was advanced all over the
world. John Grant was the planner of the Peiping First Health Station, whereas Li
Ting'an, its builder.
PMID- 27485871
TI - [Decipherment and annotation of a manuscript of Tibetan medicine in Dunhuang
scroll (Part I)-on pulse-taking].
AB - A manuscript of Tibetan medicine, P. t.1054 is recorded in the Volume 10 of
Dunhuang Tibetan Manuscripts Preserved in France, which is written in 4 pattra
leaf-like rectangular papers connected together. The content in the front side is
the pulse-taking of Tibetan medicine, and the back, on prescription. For the
pulse-taking, it deals with the manifestations, time and position for pulse
taking, paradoxical and death pulse. There is no information about the title,
author, editor, translator, copyist or collector.
PMID- 27485872
TI - [Review and reflection of the research of history of plague in modern China in
recent 25 years].
AB - Influenced by the research on history of disease abroad, the research on the
history of plague in modern China began in 1989. For the recent 25 years, the
related researches on plague mainly took place in Guangzhou, Hong Kong, the
Northeast and Shanxi, supplemented by other places, showing its clear regional
characteristic, with diversified research views, methods and application of
materials. As an important content of research on disease history, the research
of history of plague in modern China revealed obvious defects, viz. mainly
traditional and one-way or linear research, reflecting the research was still at
the borderland. Of late years, some scholars began to break through the
limitation of traditional historical concept and method, and try to apply the
interdisciplinary view for widening the research scope. With the promotion of
this academic concept, the research of plague history began " to regard history
by a bottom-up approach" , and paid more attention to the living space.
PMID- 27485873
TI - Remote care of a patient with stroke in rural Trinidad: use of telemedicine to
optimise global neurological care.
AB - We report a patient driven home care system that successfully assisted 24/7 with
the management of a 68-year-old woman after a stroke-a global illness. The
patient's caregiver and physician used computer devices, smartphones and internet
access for information exchange. Patient, caregiver, family and physician
satisfaction, coupled with outcome and cost were indictors of quality of care.
The novelty of this basic model of teleneurology is characterised by implementing
a patient/caregiver driven system designed to improve access to cost-efficient
neurological care, which has potential for use in primary, secondary and tertiary
levels of healthcare in rural and underserved regions of the world. We suggest
involvement of healthcare stakeholders in teleneurology to address this global
problem of limited access to neurological care. This model can facilitate the
management of neurological diseases, impact on outcome, reduce frequency of
consultations and hospitalisations, facilitate teaching of healthcare workers and
promote research.
PMID- 27485874
TI - Factors affecting illness in the developing world: chronic disease, mental health
and traditional medicine cures.
AB - This is a case report of a 24-year-old Ethiopian woman with a medical history of
hepatosplenic schistosomiasis. She suffers from chronic liver failure and portal
hypertension. She has been hospitalised for 'hysteria' in the past but did not
receive follow-up, outpatient treatment or psychiatric evaluation. After
discontinuing her medications and leaving her family to use holy water, a
religious medicine used by many Ethiopians, she was found at a nearby monastery.
She was non-communicative and difficult to arouse. The patient was rushed to
nearby University of Gondar Hospital where she received treatment for hepatic
encephalopathy and spontaneous bacterial peritonitis. Her illness is the result
of neglected tropical disease, reliance on traditional medicine as opposed to
biomedical services and the poor state of psychiatric care in the developing
world.
PMID- 27485875
TI - Graft-versus-host disease: unexpected presentation with simultaneous hepatitis
and pancreatitis.
AB - We report the case of a 37-year-old man with a previous bone marrow
transplantation presenting with abdominal pain, diarrhoea and jaundice.
Laboratory evaluation showed marked elevated liver enzymes, amylase and lipase
with ultrasonographic evidence of acute alithiasic pancreatitis. Liver biopsy was
compatible with graft-versus-host disease and toxic hepatitis. The patient
rapidly improved after increasing immunosuppression. Although gastrointestinal
manifestations are common in graft-versus-host disease, clinical acute
pancreatitis is rarely seen. Patients with graft versus host are seldom managed
by gastroenterologists and hepatologists. An awareness of this condition is
essential for the experienced clinician.
PMID- 27485876
TI - Jejunal intussusception caused by metastasis of a giant cell carcinoma of the
lung.
AB - A 55-year-old woman was admitted to our hospital reporting of nausea, vomiting
and anorexia. One month before admission, she had been diagnosed with lung cancer
with intestinal metastasis. A CT scan confirmed intussusception due to intestinal
metastasis and she underwent emergency laparoscopic surgery followed by resection
of the primary lung cancer. Histopathological findings of the intestinal specimen
suggested the metastasis was from a giant cell carcinoma of the lung, which had
extensive necrosis. She was still alive without recurrence 11 months after the
first surgery. Giant cell carcinoma of the lung is a rare type of non-small cell
carcinoma and intestinal metastasis is one of the unique features. This type of
tumour has such aggressive characteristics that oncological prognosis is reported
to be extremely poor. In our case, however, complete surgical resection of both
primary and metastatic tumours might result in a better outcome than has been
reported.
PMID- 27485877
TI - Ultrastructural pathology of human liver in Rift Valley fever.
AB - Rift Valley fever (RVF) is a zoonotic disease that primarily affects ruminant
animals and can also cause fatal disease in humans. In the current report, we
present the ultrastructural changes in the liver of a man aged 60 years who died
from RVF in the Aseer Central Hospital, Abha, Saudi Arabia. The main hepatic
changes by transmission electron microscopy included the presence of 95-115 nm
electron-dense particles consistent with RVF virions, nuclear condensation,
vacuolar degeneration, lipid droplet accumulation and mitochondrial damage and
dilation. There were also viral inclusion bodies with electron-dense aggregates,
dilation of intercellular spaces, damage of sinusoidal microvilli with widening
of space of Disse, dilation of bile canaliculi and increasing number of
phagolysosomes.
PMID- 27485878
TI - Recurrent SDSE bacteraemia resulting in streptococcal toxic shock syndrome in a
patient with Noonan syndrome.
AB - A 19-year-old man with chronic lymphoedema due to Noonan syndrome presented at
our hospital with septic shock and pain in his lower leg. Blood cultures were
positive for Streptococcus dysgalactiae subsp equisimilis (SDSE), resulting in a
diagnosis of cellulitis with toxic involvement. He was treated with ampicillin
for 3 weeks. Although he did well for 6 weeks, septic shock recurred. Blood
culture again revealed SDSE, with the strain being identical to the first
episode, suggesting that this infection had relapsed. He was treated with
ampicillin for 6 weeks and prophylactically with trimethoprim-sulfamethoxazole
for 12 months. Although SDSE bacteraemia occurs commonly in elderly patients,
findings in this patient showed that it can also develop in younger persons with
predisposing factors. This case also indicates that SDSE has the potential to
recur, despite generally sufficient antibiotic administration, and that patients
who experience recurrent episodes may require prolonged treatment with
antibiotics, including prophylaxis.
PMID- 27485879
TI - Ileal perforation associated with dengue in the paediatric age group: an uncommon
presentation.
AB - Acute abdomen in dengue, a common arboviral disease found in tropical and
subtropical countries, is not uncommon and can occasionally present as acute
surgical emergency requiring urgent surgical intervention. The spectrum of acute
abdomen presenting as surgical emergency in dengue infection that raises
suspicion of an abdominal catastrophe includes acute appendicitis, acute
cholecystitis, appendicitis and, rarely, intestinal perforation. All cases of
intestinal perforation including appendicular, gastric and jejunal perforation
have been reported in adult patients during the course of dengue infection.
However, intestinal perforation during the course of dengue infection in the
paediatric age group has never been reported. We report two cases of ileal
perforation in children occurring during the course of dengue infection.
PMID- 27485880
TI - Idelalisib-induced pneumonitis.
PMID- 27485881
TI - Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p
Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.
AB - Plant secondary-thickened cell walls are characterized by the presence of lignin,
a recalcitrant and hydrophobic polymer that provides mechanical strength and
ensures long-distance water transport. Exactly the recalcitrance and
hydrophobicity of lignin put a burden on the industrial processing efficiency of
lignocellulosic biomass. Both forward and reverse genetic strategies have been
used intensively to unravel the molecular mechanism of lignin deposition. As an
alternative strategy, we introduce here a forward chemical genetic approach to
find candidate inhibitors of lignification. A high-throughput assay to assess
lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and
used to screen a 10-k library of structurally diverse, synthetic molecules. Of
the 73 compounds that reduced lignin deposition, 39 that had a major impact were
retained and classified into five clusters based on the shift they induced in the
phenolic profile of Arabidopsis seedlings. One representative compound of each
cluster was selected for further lignin-specific assays, leading to the
identification of an aromatic compound that is processed in the plant into two
fragments, both having inhibitory activity against lignification. One fragment, p
iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4
HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the
building blocks of the lignin polymer. As such, we provide proof of concept of
this chemical biology approach to screen for inhibitors of lignification and
present a broad array of putative inhibitors of lignin deposition for further
characterization.
PMID- 27485884
TI - Appropriate methods to study health treatment outcomes, policies, and practices.
PMID- 27485883
TI - Evolutionary Fates and Dynamic Functionalization of Young Duplicate Genes in
Arabidopsis Genomes.
AB - Gene duplication is a primary means to generate genomic novelties, playing an
essential role in speciation and adaptation. Particularly in plants, a high
abundance of duplicate genes has been maintained for significantly long periods
of evolutionary time. To address the manner in which young duplicate genes were
derived primarily from small-scale gene duplication and preserved in plant
genomes and to determine the underlying driving mechanisms, we generated
transcriptomes to produce the expression profiles of five tissues in Arabidopsis
thaliana and the closely related species Arabidopsis lyrata and Capsella rubella
Based on the quantitative analysis metrics, we investigated the evolutionary
processes of young duplicate genes in Arabidopsis. We determined that
conservation, neofunctionalization, and specialization are three main
evolutionary processes for Arabidopsis young duplicate genes. We explicitly
demonstrated the dynamic functionalization of duplicate genes along the
evolutionary time scale. Upon origination, duplicates tend to maintain their
ancestral functions; but as they survive longer, they might be likely to develop
distinct and novel functions. The temporal evolutionary processes and
functionalization of plant duplicate genes are associated with their ancestral
functions, dynamic DNA methylation levels, and histone modification abundances.
Furthermore, duplicate genes tend to be initially expressed in pollen and then to
gain more interaction partners over time. Altogether, our study provides novel
insights into the dynamic retention processes of young duplicate genes in plant
genomes.
PMID- 27485882
TI - Auxin Is Rapidly Induced by Herbivore Attack and Regulates a Subset of Systemic,
Jasmonate-Dependent Defenses.
AB - Plant responses to herbivore attack are regulated by phytohormonal networks. To
date, the role of the auxin indole-3-acetic acid (IAA) in this context is not
well understood. We quantified and manipulated the spatiotemporal patterns of IAA
accumulation in herbivore-attacked Nicotiana attenuata plants to unravel its role
in the regulation of plant secondary metabolism. We found that IAA is strongly,
rapidly, and specifically induced by herbivore attack. IAA is elicited by
herbivore oral secretions and fatty acid conjugate elicitors and is accompanied
by a rapid transcriptional increase of auxin biosynthetic YUCCA-like genes. IAA
accumulation starts 30 to 60 s after local induction and peaks within 5 min after
induction, thereby preceding the jasmonate (JA) burst. IAA accumulation does not
require JA signaling and spreads rapidly from the wound site to systemic tissues.
Complementation and transport inhibition experiments reveal that IAA is required
for the herbivore-specific, JA-dependent accumulation of anthocyanins and
phenolamides in the stems. In contrast, IAA does not affect the accumulation of
nicotine or 7-hydroxygeranyllinalool diterpene glycosides in the same tissue.
Taken together, our results uncover IAA as a rapid and specific signal that
regulates a subset of systemic, JA-dependent secondary metabolites in herbivore
attacked plants.
PMID- 27485885
TI - Sex and gender matters: The health of women and girls determines the health of
our modern world.
PMID- 27485886
TI - Origins of Dirac cones and parity dependent electronic structures of alpha
graphyne derivatives and silagraphynes.
AB - Compared with graphene, graphyne and its derivatives possess more diversified
atomic configurations and richer electronic structures including Dirac cones
(DCs) and metallic features depending on the parity of the number of sp carbon
atoms of graphynes. This report described conceptually the process of DC
formation of alpha-graphyne within a tight-binding framework parameterized from
density functional calculations. We propose a "triple coupling" mechanism
elucidating the DC formation and some flat bands of alpha-graphynes where the
couplings among the three sp carbon chain atoms are critical. The extension of
this mechanism further explains the origins of DCs of silagraphynes and the
parity dependent electronic structures of alpha-graphyne derivatives with
extended sp carbon chains. Understanding these origins helps in tuning electronic
properties in the design of C or C-Si based nanoelectronic devices.
PMID- 27485888
TI - In Memoriam: Prof. Dr. Joachim K. Seydel.
PMID- 27485887
TI - Effect of long-range interactions on nanoparticle-induced aggregation.
AB - The process of attaching liquid media molecules to dispersed nanoparticles is
studied by numerically investigating the time evolution of the size distribution
of the emerging aggregates. Within the considered mechanism of aggregation, both
the primary particles and the resulting aggregates are assumed to connect freely
dispersing molecules, but the particles and aggregates are not allowed to self
link or self-assemble at each evolution stage of the system, due to, e.g.,
repulsive interactions. The process of random attachment of dispersing molecules
to immersed nanoparticles and aggregates is considered to be driven by attractive
long-range interactions of the van der Waals type. The molecule binding rate is,
in consequence, modeled as being dependent not only on the size and surface
morphology of the existing aggregates, but also on the van der Waals forces,
whose strength is itself treated as dependent on the aggregate size. It is
demonstrated that these forces diminish, in general, the inhomogeneity of
aggregate size. Such an effect is shown to be especially distinct when the
interaction strength is relatively large but does not increase as aggregates
increase in size, i.e., when strongly attracted media molecules functionalize the
resultant aggregates to prevent the increase of the interaction strength. This
result can be helpful to construct stable complex substances containing
aggregates with low size dispersion. Surprisingly, the evolution of aggregating
systems toward more significant inhomogeneity takes place when the interaction
strength is initially large and increases fast enough with the size of
aggregates.
PMID- 27485889
TI - BCRP Inhibition: from Data Collection to Ligand-Based Modeling.
AB - Breast Cancer Resistance Protein (BCRP, gene ABCG2) is an efflux transporter from
the ABC transporters family. It is known to be responsible for the multidrug
resistance phenomenon observed in some cancers and is also involved in drug-drug
interactions in the liver. Prediction and assessment of inhibition of BCRP is of
great interest in the drug development process. This paper presents the largest
open dataset currently available for BCRP inhibition, along with the methodology
used to compile it. It contains 978 unique compounds with corresponding
bioactivities, extracted from 47 studies. The presence of duplicates allowed us
to set up thresholds on reported activities to obtain a labelled dataset suitable
for learning classification models. Exploratory data analysis and predictive
modelling lead to the identification of substructures important for inhibition.
We find that the substructures that characterize inhibitors are in line with
known SAR relationships of BCRP inhibitors, while the substructures
characterizing the non-inhibitors are novel.
PMID- 27485890
TI - Mining Molecular Pharmacological Effects from Biomedical Text: a Case Study for
Eliciting Anti-Obesity/Diabetes Effects of Chemical Compounds.
AB - In the pharmaceutical industry, efficiently mining pharmacological data from the
rapidly increasing scientific literature is very crucial for many aspects of the
drug discovery process such as target validation, tool compound selection etc. A
quick and reliable way is needed to collect literature assertions of selected
compounds' biological and pharmacological effects in order to assist the
hypothesis generation and decision-making of drug developers. INFUSIS, the text
mining system presented here, extracts data on chemical compounds from PubMed
abstracts. It involves an extensive use of customized natural language processing
besides a co-occurrence analysis. As a proof-of-concept study, INFUSIS was used
to search in abstract texts for several obesity/diabetes related pharmacological
effects of the compounds included in a compound dictionary. The system extracts
assertions regarding the pharmacological effects of each given compound and
scores them by the relevance. For each selected pharmacological effect, the
highest scoring assertions in 100 abstracts were manually evaluated, i.e. 800
abstracts in total. The overall accuracy for the inferred assertions was over 90
percent.
PMID- 27485891
TI - Discrete Derivatives for Atom-Pairs as a Novel Graph-Theoretical Invariant for
Generating New Molecular Descriptors: Orthogonality, Interpretation and
QSARs/QSPRs on Benchmark Databases.
AB - This report presents a new mathematical method based on the concept of the
derivative of a molecular graph (G) with respect to a given event (S) to codify
chemical structure information. The derivate over each pair of atoms in the
molecule is defined as ?G/?S(vi , vj )=(fi -2fij +fj )/fij , where fi (or fj )
and fij are the individual frequency of atom i (or j) and the reciprocal
frequency of the atoms i and j, respectively. These frequencies characterize the
participation intensity of atom pairs in S. Here, the event space is composed of
molecular sub-graphs which participate in the formation of the G skeleton that
could be complete (representing all possible connected sub-graphs) or comprised
of sub-graphs of certain orders or types or combinations of these. The atom level
graph derivative index, Deltai , is expressed as a linear combination of all atom
pair derivatives that include the atomic nuclei i. Global [total or local (group
or atom-type)] indices are obtained by applying the so called invariants over a
vector of Deltai values. The novel MDs are validated using a data set of 28 alkyl
alcohols and other benchmark data sets proposed by the International Academy of
Mathematical Chemistry. Also, the boiling point for the alcohols, the adrenergic
blocking activity of N,N-dimethyl-2-halo-phenethylamines and physicochemical
properties of polychlorinated biphenyls and octanes are modeled. These models
exhibit satisfactory predictive power compared with other 0-3D indices
implemented successfully by other researchers. In addition, tendencies of the
proposed indices are investigated using examples of various types of molecular
structures, including chain-lengthening, branching, heteroatoms-content, and
multiple bonds. On the other hand, the relation of atom-based derivative indices
with (17) O NMR of a series of ethers and carbonyls reflects that the new MDs
encode electronic, topological and steric information. Linear independence
between the graph derivative indices and other 0-3D MDs is demonstrated by using
principal component analysis on a dataset of 41 heterogeneous molecules. It is
concluded that the graph derivative indices are independent indices containing
important structural information to be used in QSPR/QSAR and drug design studies,
and permit obtaining easier, more interpretable and robust mathematical models
than the majority of those reported in the literature.
PMID- 27485892
TI - Identification of Aurora-A Inhibitors by Ligand and Structure-Based Virtual
Screening.
AB - Aurora kinase A has been identified as one of the most attractive targets for
cancer therapy because of its critical role in the regulation of the cell cycle.
In order to identify active compounds with structural diversity we performed
virtual screening. 3D-QSAR pharmacophore models were developed and the best model
was used as a query for screening the databases. Ligand and structure-based
virtual screening protocol was conducted sequentially by applying the common
feature pharmacophore and molecular docking to discover potent Aurora-A
inhibitors. A total of eighty-eight compounds were selected for the in vitro
activities against various human cancer cell lines (DU145 and HT29). Considering
the activity data, we have identified seven compounds to be considered for the
next step, among which four compounds had high inhibition rate (above 50 %) at 10
uM with GI50 lower than 10 uM. Based on the cell line and enzyme assay (Aurora-A
& B) result, these four compounds were used as template/query molecule for
similarity search. The best result was obtained for similarity hit SH3. It had
IC50 of 0.578 and 11.77 uM for Aurora-A and B respectively, which implies 20-fold
selectivity over Aurora-B. The hits obtained from this screening scheme could be
potential drug candidates after further optimization.
PMID- 27485893
TI - TriClust: A Tool for Cross-Species Analysis of Gene Regulation.
AB - We present a software tool, called TriClust, for multi-way analysis of gene
expression data from paired conditions of multiple organisms. The analysis is
based on a new concept called triclustering, which is an extension of
biclustering over a third dimension that represents the organism where the
microarray experiment is performed. TriClust provides a comprehensive analysis of
co-regulated genes under a subset of experimental conditions over multiple
organisms. The results are visualized using heat-maps and the Gene Ontology (GO)
term enrichment statistics. The experimental results indicate that TriClust can
successfully identify biologically significant triclusters and promote a useful
tool for cross species analysis of gene regulation from microarray expression
data. The statistical results suggest that, when available, triclustering on
multi-organism data can result in better gene clusters in comparison to
biclustering on single-organism data. The TriClust software is publicly available
as a standalone program.
PMID- 27485894
TI - Soluble Metal-Nanoparticle-Decorated Porous Coordination Polymers for the
Homogenization of Heterogeneous Catalysis.
AB - Ultrasmall metal nanoparticles (MNPs) were decorated on soluble porous
coordination polymers (PCPs) with high metal loadings. The solubility of the
composite and the size of the MNPs can be controlled by varying the ratio of the
precursors to the supports. The soluble PCPs can serve as a platform to
homogenize heterogeneous MNPs catalysts, which exhibited excellent activity and
recyclability in C-H activation and Suzuki reactions. This strategy combines the
advantages of homogeneous and heterogeneous catalysis and may bring new
inspiration to catalysis.
PMID- 27485895
TI - Adult orthodontics: a quality assessment of Internet information.
AB - OBJECTIVES: This study evaluated the quality, reliability and readability of
information on the Internet on adult orthodontics. DESIGN: A quality assessment
of adult orthodontic websites. SETTING: Postgraduate Orthodontic Unit, Cork
University Dental School and Hospital, Cork, Ireland. METHOD: An Internet search
using three search engines (Google, Yahoo and Bing) was conducted using the terms
('adult orthodontics' and 'adult braces'). The first 50 websites from each engine
and under each search term were screened and exclusion criteria applied. Included
websites were then assessed for quality using four methods: the HON seal, JAMA
benchmarks, the DISCERN instrument and the LIDA tool. Readability of included
websites was assessed using the Flesch Reading Ease Score (FRES). RESULTS: Only
13 websites met the inclusion criteria. Most were of US origin (n = 8; 61%). The
authors of the websites were dentists (n = 5; 39%), professional organizations (n
= 2; 15%), past patients (n = 2; 15%) and unspecified (n = 4; 31%). Only 1
website displayed the HON seal and three websites contained all JAMA benchmarks.
The mean overall score for DISCERN was 3.9/5 and the mean total LIDA score was
115/144. The average FRES score was 63.1/100. CONCLUSIONS: The number of
informative websites on adult orthodontics is low and these are of moderate
quality. More accurate, high-quality Internet resources are required on adult
orthodontics. Recommendations are made as to how this may be achieved.
PMID- 27485897
TI - Physical Activity Level and Colorectal Cancer Mortality.
AB - Physical activity has been shown to reduce colorectal cancer risk. However, the
association of physical activity levels separately with colon and rectum cancer
mortality is less clear. We included 226 089 Korean in a large prospective cohort
study. We assessed the associations of physical activity levels (length,
frequency, and intensity) with colon and rectum cancer mortality using Cox
proportional hazards model. Men, but not women, who had regular physical activity
showed a lower risk of death from colon cancer. The association for high
intensity of physical activity was borderline significant in men (hazard ratio
0.67; 95% CI = 0.45-1.00 for >17.5 MET-hour/week). The associations were largely
consistent among those aged <55 years, body mass index <25 kg/m2, low high
density lipoprotein cholesterol, current smoker, and without hypertension or
history of cardiovascular disease. In conclusion, higher length or intensity of
physical activity decreased colon, but not rectum cancer mortality in men.
Regular physical activity may have beneficial effects on colon cancer survival.
PMID- 27485896
TI - Effects of carbon sources on the enrichment of halophilic polyhydroxyalkanoate
storing mixed microbial culture in an aerobic dynamic feeding process.
AB - Microbial polyhydroxyalkanoate (PHA) production serves as a substitute for
petroleum-based plastics. Enriching mixed microbial cultures (MMCs) with the
capacity to store PHA is a key precursor for low-cost PHA production. This study
investigated the impact of carbon types on enrichment outcomes. Three MMCs were
separately fed by acetate sodium, glucose, and starch as an enriching carbon
source, and were exposed to long-term aerobic dynamic feeding (ADF) periods. The
PHA production capacity, kinetics and stoichiometry of the enrichments, the PHA
composition, and the microbial diversity and community composition were explored
to determine carbon and enrichment correlations. After 350-cycle enriching
periods under feast-famine (F-F) regimes, the MMCs enriched by acetate sodium and
glucose contained a maximum PHA content of 64.7% and 60.5% cell dry weight (CDW).
The starch-enriched MMC only had 27.3% CDW of PHA. High-throughput sequencing
revealed that non-PHA bacteria survived alongside PHA storing bacteria, even
under severe F-F selective pressure. Genus of Pseudomonas and Stappia were the
possible PHA accumulating bacteria in acetate-enriched MMC. Genus of Oceanicella,
Piscicoccus and Vibrio were found as PHA accumulating bacteria in glucose
enriched MMC. Vibrio genus was the only PHA accumulating bacteria in starch
enriched MMC. The community diversity and composition were regulated by the
substrate types.
PMID- 27485898
TI - Diarrheal Diseases and Climate Change in Cambodia.
AB - The DRIP-SWICCH (Developing Research and Innovative Policies Specific to the
Water-related Impacts of Climate Change on Health) project aimed to increase the
resilience of Cambodian communities to the health risks posed by climate change
related impacts on water. This article follows a review of climate change and
water-related diseases in Cambodia and presents the results of a time series
analysis of monthly weather and diarrheal disease data for 11 provinces. In
addition, correlations of diarrheal disease incidence with selected demographic,
socioeconomic, and water and sanitation indicators are described, with results
suggesting education and literacy may be most protective against disease. The
potential impact of climate change on the burden of diarrheal disease in Cambodia
is considered, along with the implications of these findings for health systems
adaptation.
PMID- 27485900
TI - Photoprotective properties of 20(S)-protopanaxatriol, an aglycone of ginseng
saponins: Protection from ultraviolet-B radiation-induced oxidative stress in
human epidermal keratinocytes.
AB - Ginsenosides are responsible for diverse pharmacological properties ascribed to
ginseng, a plant used in traditional medicine. Ginsenosides are classified into
three categories: Protopanaxadiol, protopanaxatriol (PPT) and oleanolic acid. As
an aglycone of PPT-type ginsenosides, PPT exists in two stereoisomeric forms,
20(S)-PPT and 20(R)-PPT. The 20(S)-PPT stereoisomer is a major metabolic product
of PPT-type ginsenosides produced in the gastrointestinal tract. In the present
study, 20(S)-PPT suppressed the elevation of reactive oxygen species in HaCaT
cells following irradiation with ultraviolet (UV)-B. In addition, 20(S)-PPT
inhibited UV-B-induced gelatinase activities of matrix metalloproteinase-2 and -9
in HaCaT cells, and suppressed UV-B-induced expression and secretion of these
proteins. Accordingly, 20(S)-PPT restored the total glutathione levels in UV-B
irradiated keratinocytes. Taken together, these data indicated that 20(S)-PPT may
possess photoprotective properties that combat the effects of UV-B radiation.
PMID- 27485901
TI - Connecting polyphosphate translocation and hyphal water transport points to a key
of mycorrhizal functioning.
PMID- 27485899
TI - Structural insights into the catalysis and regulation of E3 ubiquitin ligases.
AB - Covalent attachment (conjugation) of one or more ubiquitin molecules to protein
substrates governs numerous eukaryotic cellular processes, including apoptosis,
cell division and immune responses. Ubiquitylation was originally associated with
protein degradation, but it is now clear that ubiquitylation also mediates
processes such as protein-protein interactions and cell signalling depending on
the type of ubiquitin conjugation. Ubiquitin ligases (E3s) catalyse the final
step of ubiquitin conjugation by transferring ubiquitin from ubiquitin
conjugating enzymes (E2s) to substrates. In humans, more than 600 E3s contribute
to determining the fates of thousands of substrates; hence, E3s need to be
tightly regulated to ensure accurate substrate ubiquitylation. Recent findings
illustrate how E3s function on a structural level and how they coordinate with
E2s and substrates to meticulously conjugate ubiquitin. Insights regarding the
mechanisms of E3 regulation, including structural aspects of their autoinhibition
and activation are also emerging.
PMID- 27485902
TI - 'Hide and seek' is no game in a specialized ant-plant interaction.
PMID- 27485903
TI - Diversity of Frankia in soil assessed by Illumina sequencing of nifH gene
fragments.
AB - Targeted Illumina sequencing of nitrogenase reductase (nifH) gene fragments and
analyses of pair-end reads through a modified QIIME pipeline were used to assess
the diversity of the actinomyceteous genus Frankia in three soils. Soils were
vegetated with host or non-host plants, and included locations in Illinois (ABA,
host), Colorado (CoMt, non-host), and Wisconsin (FMWI, non-host). After
filtering, seven unique sequences were recovered for soil ABA, six for CoMt, and
four sequences for FMWI. These sequences were included in a Bayesian topology
anchored by published sequence data from pure cultures of Frankia. Sequences from
all three soils showed affinities to Frankia strains from both the Alnus and
Elaeagnus host infection groups. Reads representing Casuarina-infective strains
were not detected. Four sequences from soil CoMt and five sequences from soil ABA
did not cluster, at 97% similarity, into a shared OTU that contained a cultured
relative. These results demonstrate that targeted Illumina sequencing provides an
efficient and economical method for assessing haplotype diversity of
ecofunctional genes (e.g. nifH) at the genus level in microorganisms that perform
important ecosystem functions.
PMID- 27485904
TI - Diffuse subarachnoid and intraventricular hemorrhage as the presenting sign of a
conus medullaris arteriovenous malformation: Case report.
AB - Spinal arteriovenous malformations (AVMs) are rare vascular lesions that usually
present with progressive myelopathy or less frequently, with acute neurological
deficit due to hematomyelia or spinal subarachnoid hemorrhage (SAH). There are
few reports of concomitant cerebral SAH and intraventricular hemorrhage (IVH)
following rupture of a spinal AVM. Herein, we present a rare case of conus
medullaris arteriovenous malformation, out-breaking with loss of consciousness
due to SAH and IVH.
PMID- 27485905
TI - Lysosome calcium in ROS regulation of autophagy.
AB - Lysosomes, the cell's recycling center, undergo nutrient-sensitive adaptive
changes in function and biogenesis, i.e., lysosomal adaptation. We recently
discovered that lysosomes also mediate the cell's "survival" response (i.e.,
autophagy) to oxidative stress through the activation of TFEB (transcription
factor EB), a master regulator of lysosome biogenesis and autophagy.
MCOLN1/TRPML1, the principal Ca2+ release channel on the lysosomal membrane,
serves as the redox sensor in this process. Increasing reactive oxygen species
(ROS) levels, either endogenously by mitochondrial damage or exogenously,
directly activates MCOLN1 to induce lysosomal Ca2+ release, triggering
PPP3/calcineurin-dependent TFEB nuclear translocation to enhance autophagy.
Hence, ROS may induce autophagy by activating the MCOLN1-lysosome Ca2+-TFEB
pathway, facilitating the removal of damaged mitochondria and excess ROS. Our
findings have revealed a lysosomal signaling mechanism for cells to respond to
oxidative bursts and adapt to oxidative stress.
PMID- 27485907
TI - 10th WINFOCUS World Congress on Ultrasound in Emergency and Critical Care.
PMID- 27485906
TI - Nonsuicidal Self-Injury and Suicidal Risk Among Emerging Adults.
AB - PURPOSE: Although nonsuicidal self-injury (NSSI) has been differentiated from
suicidal behavior on the basis of nonlethal intent in the Diagnostic and
Statistical Manual of Mental Disorders, NSSI often is associated with increased
suicidal risk. However, there is a paucity of large-scale longitudinal
examinations on the associations among NSSI, suicidal ideation, and suicidal
attempts, particularly among community-based samples. In the present study, we
examined whether NSSI in first-year university was associated with increased risk
for later suicidal ideation and attempts over time among students. METHODS:
Participants included 940 emerging adults (70.8% female, mean age = 19.05 years)
from a mid-sized Canadian university who volunteered to participate in a
longitudinal research project starting in first-year university (participants
were surveyed annually over five waves). RESULTS: Binary logistic regression
analyses revealed that the odds of experiencing suicidal ideation across times 2
5 were 2.04 times as high for emerging adults who engaged in NSSI at baseline
(even after controlling for suicidal ideation and attempts at baseline) as for
individuals who did not engage in NSSI. Furthermore, the odds of attempting
suicide across times 2-5 were 3.46 times as high for emerging adults who engaged
in NSSI at baseline (even after controlling for suicidal ideation and attempts at
baseline) as for individuals who did not engage in NSSI. CONCLUSIONS: Findings
suggest that the presence of NSSI in first-year university may be an important
marker of later suicidal risk, reflecting increased risk for both suicidal
ideation and attempts across the university years among emerging adults.
PMID- 27485908
TI - JAN Classic article: Mental illness, mental handicap and the nursing service
establishment - an alternative approach.
PMID- 27485909
TI - Atmospheric thorium pollution and inhalation exposure in the largest rare earth
mining and smelting area in China.
AB - Exposure to radionuclide thorium (Th) has generated widespread public concerns,
mainly because of its radiological effects on human health. Activity levels of
airborne 232Th in total suspended particulate (TSP) were measured in the vicinity
of the largest rare earth mine in China in August 2012 and March 2013. The mean
activity concentrations of 232Th in TSP ranged from 820MUBqm-3 in a mining area
in August 2012 to 39,720MUBqm-3 in a smelting area in March 2013, much higher
than the world reference of 0.5MUBqm-3. Multistatistical analysis and Kohonen's
self-organizing maps suggested that 232Th in TSP was mainly derived from rare
earth mining and smelting practices. In addition, personal inhalation exposures
to 232Th associated with respirable particulate (PM10) were also measured among
local dwellers via personal monitoring. The mean dose values for different age
groups in the smelting and mining areas ranged from 97.86 to 417MUSvyear-1 and
from 101.03 to 430.83MUSvyear-1, respectively. These results indicate that people
living in the study areas are exposed to high levels of widespread 232Th.
PMID- 27485910
TI - Exposure to polybrominated diphenyl ethers and female reproductive function: A
study in the production area of Shandong, China.
AB - Polybrominated diphenyl ethers (PBDEs) are widely used in commercial and
household products. Few human studies have examined the effects of PBDE exposure
on female reproductive function. We recruited 207 pregnant women when they were
admitted for labor from September 2010 to February 2012 as part of a birth cohort
study, the Laizhou Wan Birth Cohort study. Maternal sera were analyzed for eight
PBDE congeners (BDE-28, -47, -85, -99, -100, -153, -154, and -183) and four sex
hormones. BDE-153 exhibited the highest serum level (median 4.67ng/g lipid),
followed by BDE-99 (median 3.45ng/g lipid) and BDE-28, -47, and -100 (medians
near 2ng/g lipid). BDE-28, -47, -99, -100, and -153 were the most frequently
detected (>90%) congeners. Follicle-stimulating hormone (FSH) levels were
negatively associated with PBDE exposure. For each natural log unit increase in
BDE-47, 100, and ?5PBDEs, FSH levels changed -1.19IU/L (95% confidence interval
[CI]: -1.32, -1.02), -1.17IU/L (95%CI: -1.36, -1.01) and -1.26IU/L (95%CI: -1.55,
-1.02) respectively. BDE-85, -153, and -183 were associated with adverse
reproductive effects, including an increased risk of threatened abortion (odds
ratio [OR] [95% CI]: 1.30 [1.03, 1.62], 1.04 [1.01, 1.08], and 1.03 [1.01, 1.06],
respectively). BDE-153 was associated with an increased risk of premature birth
(adjusted OR [95% CI]:1.05 [1.01, 1.09]), and BDE-28 was associated with longer
time to pregnancy (adjusted OR [95% CI]: 1.34 [1.03, 1.76]). These findings
suggest that maternal PBDE exposure may be inversely associated with female
reproductive function.
PMID- 27485911
TI - Loneliness and related factors among people with schizophrenia in Japan: a cross
sectional study.
AB - WHAT IS KNOWN ABOUT THE SUBJECT?: Loneliness among people diagnosed with
schizophrenia is a serious problem. Recent studies have focused on the
loneliness; however, no study has examined the relationships between loneliness
and both individual and environmental factors comprehensively. WHAT THIS PAPER
ADDS TO EXISTING KNOWLEDGE?: The main results indicated that the community
dwelling people diagnosed with schizophrenia in Japan as well as in other
countries experienced higher levels of loneliness. Both individual and
environmental factors were related to loneliness. Increasing the self-efficacy
for community life and self-esteem of individual factors, and not being socially
isolated and increasing community integration of environmental factors would
improve their loneliness. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Health
practitioners, in particular, public health nurses in mental health care, should
work to develop a partnership with people diagnosed with schizophrenia, their
family members, friends and other community-dwelling people in order to decrease
and prevent loneliness. For individuals diagnosed with schizophrenia,
interventions by cooperating with community resources and using the technique of
nurses to assist them with continuous community activity could be useful. For
environmental interventions, population approach such as developing daily
programmes which family members can participate in, and cooperating with
educational institutions and community events could have a positive effects.
ABSTRACT: Introduction Loneliness among people diagnosed with schizophrenia
living in communities can decrease quality of life and may contribute to suicide.
Aim The aim of this study was to examine the levels of loneliness among Japanese
people diagnosed with schizophrenia and to identify individual and environmental
factors related to their loneliness. Method A cross-sectional survey was
conducted with 264 people diagnosed with schizophrenia who use local activity
support centres in urban areas. The self-administered questionnaires included
questions on loneliness, demographic characteristics, individual factors
including self-efficacy for community life and self-esteem, and environmental
factors including social isolation, community integration and service use.
Results The study results indicated that people diagnosed with schizophrenia in
Japan experience higher levels of loneliness, corroborating results from other
countries. Multiple regression analysis showed that a lower level of self
efficacy for community life, self-esteem, community integration and social
isolation predicted a higher level of loneliness, accounting for 55.3% of
variance. Implications for Practice Public health nurses in mental health care in
Japan can work with individuals diagnosed with schizophrenia and communities
using the technique to assist them with continuous activity and cooperating with
community resources and educational institutions in order to decrease and prevent
loneliness.
PMID- 27485912
TI - Graphene oxide/ferroferric oxide/polyethylenimine nanocomposites for Congo red
adsorption from water.
AB - Graphene oxide/ferroferric oxide/polyethylenimine (GO/Fe3O4/PEI) nanocomposites
were synthesized by an in situ growth of Fe3O4 nanoparticles on GO sheets, and
then modified by PEI. The GO/Fe3O4/PEI nanocomposites showed extremely high
removal efficiency for anionic dye Congo Red (CR) due to the positively charged
PEI molecules (methylene blue was also tested but with low adsorption capacity
due to its cationic property). The CR removal capacity was 574.7 mg g-1, higher
than most of reported results. The adsorption kinetics could be well described by
a pseudo-second-order model. Furthermore, GO/Fe3O4/PEI nanocomposites could be
easily recycled by magnetic separation. The removal efficiency remained above 70%
after five cycles.
PMID- 27485914
TI - Regional three-dimensional deformation of human Achilles tendon during
conditioning.
AB - Our understanding of in vivo Achilles tendon (AT) conditioning is limited to two
dimensional ultrasound measures of longitudinal deformation of the whole tendon.
This study investigated the regional three-dimensional (3D) deformation of the AT
during conditioning. Eighteen ATs were scanned using 3D freehand ultrasound
during 10 successive 25 s submaximal (50%) voluntary isometric plantarflexion
contractions. Longitudinal strain was assessed for the whole AT, aponeurosis, and
free AT and transverse strain was assessed for the proximal-, mid-, and distal
portions of the free AT. Longitudinal conditioning of the whole AT was primarily
driven by creep response of the free AT and transverse conditioning was greatest
for the mid-portion of the free AT. Whole and free AT longitudinal strain
increased up to the third contraction and were accompanied by a corresponding
reduction in free AT cross-sectional area (CSA) strain in proximal-, mid-, and
distal-portions. No significant changes in aponeurosis strain or tendon volume
were detected between contractions. These findings suggest that conditioning
alters free AT shape, with increased tendon length attained at the expense of
reduction in free AT CSA. Although AT experiences different amounts of strain in
different regions, the number of contractions required to reach steady-state
strain during conditioning is uniform throughout the tendon.
PMID- 27485913
TI - Differences in fairness and trust between lean and corpulent men.
AB - BACKGROUND: Employment disparities are known to exist between lean and corpulent
people, for example, corpulent people are less likely to be hired and get lower
wages. The reasons for these disparities between weight groups are not completely
understood. We hypothesize (i) that economic decision making differs between lean
and corpulent subjects, (ii) that these differences are influenced by peoples'
blood glucose concentrations and (iii) by the body weight of their opponents.
METHODS: A total of 20 lean and 20 corpulent men were examined, who performed a
large set of economic games (ultimatum game, trust game and risk game) under
euglycemic and hypoglycemic conditions induced by the glucose clamp technique.
RESULTS: In the ultimatum game, lean men made less fair decisions and offered 16%
less money than corpulent men during euglycemia (P=0.042). During hypoglycemia,
study participants of both weight groups accepted smaller amounts of money than
during euglycemia (P=0.031), indicating that a lack of energy makes subjects to
behave more like a Homo Economicus. In the trust game, lean men allocated twice
as much money to lean than to corpulent trustees during hypoglycemia (P<0.001).
Risk-seeking behavior did not differ between lean and corpulent men. CONCLUSION:
Our data show that economic decision making is affected by both, the body weight
of the participants and the body weight of their opponents, and that blood
glucose concentrations should be taken into consideration when analyzing economic
decision making. When relating these results to the working environment, the
weight bias in economic decision making may be also relevant for employment
disparities.
PMID- 27485915
TI - Mapping painDETECT, a neuropathic pain screening tool, to the EuroQol (EQ-5D-3L).
AB - PURPOSE: To map relationships between painDETECT, a neuropathic pain (NeP)
screening tool, and EQ-5D-3L health status in a real-world setting. METHODS:
Patients with physician-confirmed NeP and painDETECT score classifications of
nociceptive (n = 79), transitional (n = 141), and NeP (n = 386) completed the
EuroQol (EQ-5D-3L), which evaluates Mobility, Self-Care, Usual Activities,
Pain/Discomfort, and Anxiety/Depression with three ordinal response levels ("no
problem," "some problems," or "extreme problems/unable to do"), and has a health
status thermometer (0 = worst health, 100 = perfect health). Multiple linear and
logistic regressions were performed (adjusted for age, gender, race, ethnicity,
time since NeP diagnosis, number of comorbidities, NeP conditions). RESULTS:
Unadjusted mean (+/-SD) EQ-5D-3L thermometer scores showed poorer health status
across painDETECT classifications from nociceptive (67.3 +/- 22.1) to
transitional (62.3 +/- 20.9) to NeP (53.7 +/- 21.8), as did utility scores, 0.695
+/- 0.206, 0.615 +/- 0.216, and 0.506 +/- 0.216. In general, the highest odds of
health problems were observed for NeP and the lowest for nociceptive, e.g., the
NeP group was 6.2 (95 % confidence interval 3.4-11.4) times as likely to have a
more severe problem of Usual Activities compared with the nociceptive group.
Relative to nociceptive and transitional, NeP had lower adjusted mean thermometer
scores, by 12.1 (P < 0.0001) and 7.8 (P = 0.0004) points, respectively, and lower
mean utility scores by 0.157 (P < 0.0001) and 0.092 points (P < 0.0001).
CONCLUSIONS: This study, the first to map relationships between painDETECT and
the EQ-5D-3L in a real-world setting, indicates that the patient burden with
respect to pain classification can be characterized and quantified by decrements
in health status overall and in specific domains. These data support the
psychometric soundness of painDETECT, enhancing its use in pain management.
PMID- 27485916
TI - Autism spectrum disorder: family quality of life while waiting for intervention
services.
AB - PURPOSE: Families of children with autism spectrum disorder (ASD) often
experience high levels of stress; it is important to investigate the family
quality of life (FQOL) to understand how to serve the entire family, not just the
child. The purpose of this investigation was to determine: (a) how families with
a child with ASD view their overall FQOL and (b) what aspects of everyday life
have the greatest influence on the FQOL? METHODS: A survey designed to asses FQOL
was mailed to all families (n = 454) of children with ASD (0-18 years) waiting
for government-funded services. Results from 151 surveys were examined (31 %
response rate). Descriptive on all variables, ordinal logistic regression, and t
tests were used to analyze the data. RESULTS: The most influential factors on
FQOL were whether the child with ASD had a major health concern, whether the
family's needs were met by disability-related services, and whether there were
opportunities to engage in leisure and recreation activities. CONCLUSIONS:
Families on waitlists experience challenges in FQOL influenced by the health of
the family members; this is implicitly important for service agencies and
providers. Future research should continue to explore how access to disability
related services impacts FQOL; and how these associations may be moderated by
contextual factors such as socioeconomic status, health of child and family
members, access and engagement in recreation, and severity of the child's needs.
PMID- 27485917
TI - Chemical Twinning of Salt and Metal in the Subnitridometalates Ba23 Na11 (MN4 )4
with M=V, Nb, Ta.
AB - The subnitridometalates Ba23 Na11 (MN4 )4 (M=V, Nb, Ta) crystallize in a new
structure type, which shows ionic ortho-nitridometalate anions and motifs from
simple (inter)metallic packings: Na-centered [Na8 ] cubes as cutouts of the bcc
structure of elemental Na and Na-centered [Ba10 Na2 ] icosahedra as found in
Laves phases, for example. Single-crystal and powder X-ray diffraction studies in
combination with quantum-chemical calculations of the electronic structure and
Raman spectroscopy support the characterization of the subnitridometalates as
"chemical twins". They consist of independent building units with locally
prevalent ionic or metallic bonding in an overall metallic compound.
PMID- 27485918
TI - Novel variant in the TP63 gene associated to ankyloblepharon-ectodermal dysplasia
cleft lip/palate (AEC) syndrome.
AB - BACKGROUND: Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome
is a disorder resulting from anomalous embryonic development of ectodermal
tissues. There is evidence that AEC syndrome is caused by mutations in the TP63
gene, which encodes the p63 protein. This is an important regulatory protein
involved in epidermal proliferation and differentiation. MATERIALS AND METHODS:
Genome sequencing was performed in DNA from peripheral blood leukocytes of a
newborn with AEC syndrome and her parents. Variants were searched in all coding
exons and intron-exon boundaries of the TP63 gene. RESULTS: A heterozygous
missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn
patient. No variants were found in either of the parents. CONCLUSIONS: We
identified a previously unreported variant in TP63 gene which seems to be
involved in the somatic malformations found in the AEC syndrome. The absence of
this variant in both parents suggests that the variant appeared de novo.
PMID- 27485919
TI - Effect of Astaxanthin, Vitamin E, and Vitamin C in Combination with Calorie
Restriction on Sperm Quality and Quantity in Male Rats.
AB - The aim of this study was to investigate the effect of calorie restriction and
dietary antioxidant supplementation, separately or in combination, on the quality
and quantity of sperm in male rats. Forty male rats were randomly allocated to
four groups of 10 animals each, and fed for at least 86 days with an ad libitum
diet (group 1), a restricted diet (group 2), an ad libitum diet and astaxanthin,
vitamin E, and vitamin C supplements (group 3), or a restricted diet with
astaxanthin, vitamin E, and vitamin C supplements (group 4). At the end of the
study period, sperm count and motility were determined with a hemocytometer, and
differences between the groups were analyzed by analysis of variance. In
addition, total antioxidant capacity and 8-epi prostaglandin F2 alpha were
measured at the beginning and end of the study period with an enzyme-linked
immunosorbent assay method. After 86 days, a significantly higher sperm count was
seen in group 4 compared to other groups. The percentage of immotile sperm was
significantly decreased in groups 2, 3, and 4 compared to group 1. A significant
increase in total antioxidant capacity was observed in group 3 (p = 0.02) and
group 4 (p = 0.02) compared to groups 1 and 2. Antioxidant supplementation with
or without calorie restriction had no significant effect on the serum isoprostane
level in any group. Astaxanthinin, combined with vitamin E, vitamin C, and
calorie restriction, was able to ameliorate, in part, infertility in male rats.
PMID- 27485920
TI - Analysis of adaptive mutations selected during the consecutive passages of
hepatitis E virus produced from an infectious cDNA clone.
AB - To characterize the genomic mutations of hepatitis E virus (HEV) during
consecutive passages associated with adaptation to growth in cell culture, a
cloned genotype 3 HEV [pJE03-1760F/wt, starting virus (SV)] was passaged 10 times
in A549 cells, and the entire genomic sequence of the passage 10 (P10) progeny
was determined. Compared to SV, P10 virus possessed two non-synonymous (T2808C
and A5054G) and four synonymous mutations (C1213T, T2557C, C3118T and C4435T) in
the ORF1. Full-length infectious cDNA clones with a single, double (T2808C and
A5054G), or all six mutations, identical to P10, were constructed, and their
replication capacity was compared. Four (C1213T, T2557C, T2808C and A5054G) of
the six viruses with a single mutation grew more efficiently than SV. The P10
virus propagated more rapidly and grew more efficiently than SV and T2808C+A5054G
and reached a higher viral load (95.1- and 8.5-fold, respectively) at 20days post
inoculation. An immunofluorescence analysis revealed that a high percentage
(>80%) of cells inoculated with the P10 virus expressed ORF2 proteins, while
relatively low percentages (nearly 30% or 5%) inoculated with T2808C+A5054G or
SV, respectively, expressed ORF2 proteins. We found that not only non-synonymous
but also synonymous HEV mutations are independently associated with increased
virus production.
PMID- 27485921
TI - Cyclophilin and enolase are the most prevalent conidial antigens of Lomentospora
prolificans recognized by healthy human salivary IgA and cross-react with
Aspergillus fumigatus.
AB - PURPOSE: The study of the immunocompetent airways immune response may provide
important information to improve the therapeutic efficacy against Lomentospora
(Scedosporium) prolificans. So, this study aimed to identify the most prevalent
conidial antigens of this multiresistant fungus recognized by healthy human
salivary immunoglobulin A, and to study their expression and cross-reactivity
with other fungal species. EXPERIMENTAL DESIGN: Twenty saliva from
immunocompetent donors were used to detect and identify the immunoreactive
proteins by 2D immunoblotting and LC-MS/MS. Moreover, anti-Aspergillus antibodies
were purified to study their cross-reactivity. RESULTS: Ten proteins of L.
prolificans conidia showed reactivity with more than 50% of the saliva samples.
Among them, cyclophilin and enolase were the most prevalent antigens recognized
by 85 and 80% of the samples, respectively. These enzymes were also identified on
the cell wall surface of L. prolificans and on the immunomes of Scedosporium
apiospermum and Scedosporium aurantiacum. Additionally, they showed cross
reactivity with the most common pathogenic filamentous fungus Aspergillus
fumigatus. CONCLUSION AND CLINICAL RELEVANCE: These results show that the
immunocompetent immune response might offer a pan-fungal recognition of conserved
antigens such as enolase and cyclophilins, making them potential candidates for
study as therapeutic targets.
PMID- 27485922
TI - Effect of WC/Co coherency phase boundaries on Fracture toughness of the
nanocrystalline cemented carbides.
AB - The effect of coherency WC/Co phase boundaries on the fracture toughness of the
nanocrystalline WC-Co cemented carbides is studied by MD simulation method. The
simulation results show that the nanocrystalline WC-Co cemented carbides with
coherency WC/Co phase boundaries has higher fracture toughness than that without
coherency WC/Co phase boundaries. Moreover, the mechanism of why coherency WC/Co
phase boundaries can improve the fracture toughness of the nanocrystalline
cemented carbides is also investigated. It is found the fact that the separation
energy of the coherent WC/Co phase boundary is larger than that of the incoherent
WC/Co phase boundaries is the main reason for this excellent mechanical property.
PMID- 27485923
TI - Regulatory Factors Influencing Usage of Retinal Pharmaceuticals: A Look Both Home
and Abroad.
PMID- 27485924
TI - [Not Available].
PMID- 27485925
TI - [Not Available].
PMID- 27485926
TI - [Joint Conference of the German Society for Medical Sociology and the German
Society for Medical Psychology from September 28 - 30, 2016].
PMID- 27485927
TI - [On the Relationship between EMDR and Eye Movements - An Analysis of the Current
State of Neurobiological Research].
AB - EMDR is an effective treatment for people diagnosed with posttraumatic stress
disorder. The traditional technique of EMDR combines the activation of
distressing reminders with guided rhythmic eye movements. The present article
reviews the current state of research on the neurobiological correlates of the
eye movements occurring during EMDR. The distinction between saccades and smooth
pursuit eye movements allows for detailed analyses of ocular motor connections
with cerebral networks of attention, memory and emotion. Possible consequences
for research and clinical practice with EMDR are discussed.
PMID- 27485928
TI - [Evaluation of the One-Year Multimodal Weight Loss Program DOC WEIGHT(r) 1.0 for
Obesity Class II and III].
AB - According to treatment guidelines, treatment for obesity (body mass index
[BMI]>=30.0 kg/m(2)) comprises nutritional, physical, and behavioral
interventions. However, evidence-based programs for the treatment of severe
obesity are rare. In an uncontrolled study, a total of 190 participants
(BMI>=35.0 kg/m(2)) of the one-year multimodal treatment program DOC WEIGHT((r))
1.0 were assessed at pre- (t0) and post-intervention (t1) as well as at 1-year
follow-up (t2). Results revealed significant improvements from t0 to t1 in body
weight, waist circumference, eating disorder psychopathology, and quality of life
that persisted to t2. Long-term multimodal outpatient treatment for severe
obesity focusing on behavior modification is promising, however, high rates of
loss to follow-up limit explanatory power. To improve evidence, consecutive
evaluation is intended.
PMID- 27485929
TI - [Feedback on Cognitive Remediation Therapy from Adolescents with Anorexia Nervosa
- A Qualitative Study].
AB - BACKGROUND: Cognitive remediation therapy (CRT) is a relatively new therapy for
patients with anorexia nervosa (AN). There is an increased demand to include the
patient view during the evaluation of treatment programs. So far, there is no
structured evaluation of the subjective view of adolescents with AN on CRT
available. METHODS: 20 patients with AN between the ages of 12 and 18 years
completed 10 CRT sessions. 19 patients (age: 15.6+/-1.3; BMI-percentile: 2.4+/
3.5) filled out a feedback questionnaire on their subjective CRT experience. The
positive and negative aspects of CRT from a patient's perspective were inducted
from the feedback material using the 'Qualitative content analysis' from Mayring,
allowing the data to be summarized into different categories. The software
program MAXQDA 11 was used for the data analysis. RESULTS: The final category
system consisted of 6 general categories, which in turn were summarized into 4
main categories: "general therapy perception", "content specific therapy
perception", "relationship to everyday life" and "relationship with CRT
therapist". 10 patients described CRT (53%) as 'fun'. 12 patients (63%) noticed
positive changes in their everyday lives, which they attributed to their
participation in CRT. 4 patients (21%) were not able to notice any changes in
their everyday lives. 3 patients (16%) valued the good atmosphere during the CRT
sessions and 6 patients (32%) found CRT to be a welcome distraction from their
daily lives on the ward. 5 patients (26%) mentioned that CRT was too demanding
and that difficulties arose during their reflection on thinking styles.
DISCUSSION: Overall, CRT is evaluated positively by adolescent patients with AN.
A small number of patients reports difficulties with CRT and experiences CRT as
strenuous. This positive evaluation of CRT is in line with results from the few
qualitative studies in adults with AN. Due to a potential social desirability
bias, the patient's perspective should be interpreted with slight caution.
CONCLUSION: CRT is received well by adolescents with AN and poses an interesting,
new therapy module in the eating disorder field.
PMID- 27485930
TI - [A Cognitive Behavioural Group Therapy Manual for Elderly People with Type 2
Diabetes and Minor Depression].
AB - Diabetes in the elderly is often associated with depressive symptoms. This
comorbidity leads to a higher risk for diabetes related complications, disability
and mortality and can be observed not only in major depression but also in
subthreshold or minor depression. Specific psychological interventions for this
high-risk patient group were not available yet. Therefore, we developed a
diabetes specific cognitive behavioral group intervention for elderly outpatients
with subthreshold or minor depression and type 2 diabetes within a randomized
controlled trial. The treatment goals focus on improvement in health related
quality of life, depression symptoms, glycemic control and cost effectiveness. In
this article we give an overview of the manualized treatment program.
PMID- 27485931
TI - [Psychosocial Therapies in Severe Mental Illness: Outlook on the Update of the
DGPPN-S3-Guideline].
AB - The Psychiatry Enquete turned 40 years old last year. The S3 guideline
"Psychosocial therapies for severe mental illness" is considered to be the last
milestone of the reform to date. This paper highlights new impulses resulting
from the S3 guideline for psychiatric care and provides an outlook on the update,
expected in 2017. Many of the interventions reported in the S3 guideline are now
supported by a broader evidence base.
PMID- 27485932
TI - Transformation by different oncogenes relies on specific metabolic adaptations.
AB - Metabolic adaptations are emerging as common traits of cancer cells and tumor
progression. In vitro transformation of NIH 3T3 cells allows the analysis of the
metabolic changes triggered by a single oncogene. In this work, we have compared
the metabolic changes induced by H-RAS and by the nuclear resident mutant of
histone deacetylase 4 (HDAC4). RAS-transformed cells exhibit a dominant aerobic
glycolytic phenotype characterized by up-regulation of glycolytic enzymes,
reduced oxygen consumption and a defect in complex I activity. In this model of
transformation, glycolysis is strictly required for sustaining the ATP levels and
the robust cellular proliferation. By contrast, in HDAC4/TM transformed cells,
glycolysis is only modestly up-regulated, lactate secretion is not augmented and,
instead, mitochondrial oxygen consumption is increased. Our results demonstrate
that cellular transformation can be accomplished through different metabolic
adaptations and HDAC4/TM cells can represent a useful model to investigate
oncogene-driven metabolic changes besides the Warburg effect.
PMID- 27485933
TI - Prevalence and risk factors associated with the patency of ductus arteriosus in
premature neonates: a prospective observational study from Iran.
AB - BACKGROUND: Patent ductus arteriosus (PDA) is a common problem in the preterm
infants. The frequency of PDA varies with the time of study, and the
characteristics of the population included in the trial. AIMS AND OBJECTIVE: To
determine the prevalence and prenatal risk factor associated with PDA. METHODS
AND MATERIAL: This prospective cross-sectional observational study was carried
out on neonates who had gestational age below 37 weeks during the period of
February 2014 to September 2014. Echocardiography was done at 4-7 days of
postnatal age. The association between prenatal risk factors of the infants and
the PDA was studied. RESULTS: From a total population of 200 enrolled infants
22.5% had PDA. The mean gestational age and birth weight were 32.1 +/- 2.65
(weeks) and 1741 +/- 622.85 (g), respectively. Maternal antepartum hemorrhage,
respiratory distress syndrome (RDS), need for surfactant, birth weights, female
gender, gestational age, Apgar scores at 1 and 5 min of the infants were found to
be associated with the prevalence of PDA. CONCLUSION: Several prenatal factors
make preterm newborns susceptible to PDA. These risk factors should be identified
as soon as possible for early commencement of PDA management.
PMID- 27485934
TI - A Social Media Peer Group Intervention for Mothers to Prevent Obesity and Promote
Healthy Growth from Infancy: Development and Pilot Trial.
AB - BACKGROUND: Evidence increasingly indicates that childhood obesity prevention
efforts should begin as early as infancy. However, few interventions meet the
needs of families whose infants are at increased obesity risk due to factors
including income and maternal body mass index (BMI). Social media peer groups may
offer a promising new way to provide these families with the knowledge,
strategies, and support they need to adopt obesity prevention behaviors.
OBJECTIVE: The aim of this study is to develop and pilot test a Facebook-based
peer group intervention for mothers, designed to prevent pediatric obesity and
promote health beginning in infancy. METHODS: We conducted in-depth semi
structured interviews with 29 mothers of infants and focus groups with 30
pediatric clinicians, to inform the development of a theory-based intervention.
We then conducted a single-group pilot trial with 8 mothers to assess its
feasibility and acceptability. All participants were recruited offline at
pediatric primary care practices. Participants in the pilot trial joined a
private Facebook group, moderated by a psychologist, with a weekly video-based
curriculum, and also had the option to meet at a face-to-face event. Within the
Facebook group, mothers were encouraged to chat, ask questions, and share photos
and videos of themselves and babies practicing healthy behaviors. Consistent with
the literature on obesity prevention, the curriculum addressed infant feeding,
sleep, activity, and maternal well-being. Feasibility was assessed using the
frequency and content of group participation by mothers, and acceptability was
measured using online surveys and phone interviews. RESULTS: Based on preferences
of mothers interviewed (mean BMI 35 kg/m(2), all Medicaid-insured, mean age 27,
all Black), we designed the intervention to include frequent posts with new
information, videos showing parents of infants demonstrating healthy behaviors,
and an optional face-to-face meeting. We developed a privacy and safety plan that
met the needs of participants as well as the requirements of the local
institutional review board (IRB), which included use of a "secret" group and
frequent screening of participant posts. Clinicians, 97% (29/30) women and 87%
(26/30) pediatricians, preferred no direct involvement in the intervention, but
were supportive of their patients' participation. In our 8-week, single group
pilot trial, all participants (mean BMI 35 kg/m(2), all Medicaid-insured, mean
age 28, all Black) viewed every weekly video post, and interacted frequently,
with a weekly average of 4.4 posts/comments from each participant. All
participant posts were related to parenting topics. Participants initiated
conversations about behaviors related to healthy infant growth including solid
food introduction, feeding volume, and managing stress. All 8 pilot group
participants reported that they found the group helpful and would recommend it to
others. CONCLUSIONS: Our methodology was feasible and acceptable to low-income
mothers of infants at high risk of obesity, and could be adapted to implement
peer groups through social media for underserved populations in varied settings.
CLINICALTRIAL: ClinicalTrials.gov NCT01977105;
https://clinicaltrials.gov/ct2/show/NCT01977105 (Archived by WebCite at
http://www.webcitation.org/6iMFfOBat).
PMID- 27485935
TI - (1)H NMR metabolomic study of auxotrophic starvation in yeast using Multivariate
Curve Resolution-Alternating Least Squares for Pathway Analysis.
AB - Disruption of specific metabolic pathways constitutes the mode of action of many
known toxicants and it is responsible for the adverse phenotypes associated to
human genetic defects. Conversely, many industrial applications rely on metabolic
alterations of diverse microorganisms, whereas many therapeutic drugs aim to
selectively disrupt pathogens' metabolism. In this work we analyzed metabolic
changes induced by auxotrophic starvation conditions in yeast in a non-targeted
approach, using one-dimensional proton Nuclear Magnetic Resonance spectroscopy
((1)H NMR) and chemometric analyses. Analysis of the raw spectral datasets showed
specific changes linked to the different stages during unrestricted yeast growth,
as well as specific changes linked to each of the four tested starvation
conditions (L-methionine, L-histidine, L-leucine and uracil). Analysis of changes
in concentrations of more than 40 metabolites by Multivariate Curve Resolution -
Alternating Least Squares (MCR-ALS) showed the normal progression of key
metabolites during lag, exponential and stationary unrestricted growth phases,
while reflecting the metabolic blockage induced by the starvation conditions. In
this case, different metabolic intermediates accumulated over time, allowing
identification of the different metabolic pathways specifically affected by each
gene disruption. This synergy between NMR metabolomics and molecular biology may
have clear implications for both genetic diagnostics and drug development.
PMID- 27485936
TI - Characteristics and clinical outcomes of patients undergoing fertility treatment
by double gamete donation.
AB - The number of women receiving in vitro fertilization cycles with both oocyte and
sperm donation (double donation; DD) has grown globally in the last decade. The
aim of this retrospective study, which included 1139 DD cycles, was to describe
the characteristics of patients receiving DD and the outcomes of this assisted
reproductive treatment. A cluster analysis identified couple 'status' as the main
variable in dividing patients into categories. Three such status groups were
identified for further analysis: (i) single women (SW), that is women without a
partner either male or female; (ii) women with a male partner (MP); (iii) women
with a female partner (FP). SW were significantly older (43.9) than patients with
a MP (40.4) and a FP (41.3). Women with a male or FP comprised fewer patients
with no previous assisted reproductive technology cycles (18.4% and 25.7%,
respectively) compared to SW (43.5%). The proportion of patients without children
before treatment was significantly different between SW (94.7%) and women with a
MP (87.2%). There were no differences in clinical outcomes among the three groups
studied. Biochemical pregnancy rate was 58.2% in SW, 58.4% in women with a MP and
64.9% in women with a FP. For the same groups, clinical pregnancy rates were
50.2%, 49.4% and 55.4%, while 'take-home baby' rates were 36.6%, 38.9% and 40.3%.
Multiple birth and caesarean section rates were not different among the groups,
with twinning rates 21.1%, 30.4% and 36%, and caesarean section rates 25.6%, 24%
and 26.4% for SW, women with MP and women with FP, respectively.
PMID- 27485937
TI - Paediatric Eye Services: How Much of the Workload Is Amblyopia-Related?
AB - AIMS: The proportion of patients seen by the paediatric eye service that attend
for reasons related to amblyopia has not been quantified. The purpose of this
study was to quantify the proportion of patients seen in the paediatric eye
service attending for reasons related to amblyopia. METHODS: Records of all eye
appointments of children attending the Hillingdon Hospitals NHS Foundation Trust
and St Mary's Hospital Imperial College Healthcare NHS Trust over one month in
2009 were examined to determine the diagnosis and reason for attendance. RESULTS:
Seven hundred and four patients had appointments booked at St Mary's and
Hillingdon in March 2009. The fail-to-attend rates were not significantly
different at the 2 sites (19% at St Mary's and 9% at Hillingdon; P=0.75). Of the
704 patients, 533 (St Mary's, 252 [75%]; Hillingdon, 281 [76%]) were attending
for amblyopia-related reasons. Of the overall 982 booked appointments, 770 (79%)
were amblyopia-related. CONCLUSIONS: Amblyopia diagnosis and management is
clearly the most common cause of attendance to the paediatric eye service,
accounting for over three-quarters of outpatient visits.
PMID- 27485938
TI - Low-dose testosterone alleviates vascular damage caused by castration in male
rats in puberty via modulation of the PI3K/AKT signaling pathway.
AB - The aim of the present study was to investigate the effect of testosterone on
glucolipid metabolism and vascular injury in male rats, and examine the
underlying molecular mechanisms. A total of 40 male Sprague-Dawley rats were
divided into a control group (n=10), high-fat-diet + castration group (n=10),
high-fat-diet + castration + low dose testosterone group (n=10), and high-fat
diet + castration + high dose testosterone group (n=10). Hematoxylin and eosin
staining was performed to evaluate the morphology of the thoracic aortic tissues.
Immunohistochemical staining was used to detect biomarkers of the
phosphoinositide 3-kinase (PI3K) signaling pathway. The mRNA and protein
expression levels of PI3K, AKT, insulin receptor substrate-1 (IRS-1), glucose
transporter type 4 (GLUT-4), nuclear factor (NF)-kappaB and tumor necrosis factor
(TNF)-alpha in the aortas were determined using quantitative polymerase chain
reaction and Western blot analyses, respectively. Apoptosis in the aortic tissues
was detected using a TUNEL assay. Castration induced apoptosis in the animals fed
a high-fat-diet, whereas low dose testosterone replacement ameliorated the
apoptosis in the aorta. However, the levels of apoptosis was more severe
following high-dose testosterone treatment. Low-dose testosterone induced
upregulation in the levels of IRS-1, AKT, GLUT-4 protein, NF-kappaB, TNF-alpha
and PI3K, compared with those in the animals fed a high-fat diet following
castration. A high dose of testosterone resulted in a significant decrease in the
levels of IRS-1, AKT, GLUT-4, NF-kappaB, TNF-alpha and PI3K. Compared with the
rats in the high-fat diet + castration group, a low dose of testosterone induced
upregulation in the mRNA levels of IRS-1, AKT and GLUT-4, and downregulation of
the mRNA levels of NF-kappaB, TNF-alpha and PI3K. A high dose of testosterone
resulted in a significant decrease in the levels of IRS-1, AKT and GLUT-4, and
marked increases in the mRNA levels of NF-kappaB, TNF-alpha and PI3K, compared
with the low dose group. Castration induced marked disorders of glucolipid
metabolism and vascular injuries in the pubescent male rats. Low-dose
testosterone treatment was found to ameliorate the vascular damage caused by
castration via the PI3K/AKT signaling pathway.
PMID- 27485939
TI - Co-expression of autophagic markers following photodynamic therapy in SW620 human
colon adenocarcinoma cells.
AB - Photodynamic therapy (PDT) is a minimally invasive cancer treatment. It involves
the combination of a photosensitizer and light of a specific wavelength to
generate singlet oxygen and other reactive oxygen species that lead to tumor cell
death. Autophagy is one of the pathways that tumor cells undergo during
photodamage and it is common in photodynamic therapy. The aim of this study was
to examine the effect of in vitro PDT on the expression of autophagy-related
proteins, autophagy related 7 (Atg7), light chain 3 (LC3) and Beclin-1. Human
SW620 colon carcinoma cells were treated with 5-aminolevulinic acid (ALA)-based
PDT at a dose of 3 mM. The irradiation was performed using 4.5 J/cm2 total light
and a fluence rate of 60 mW/cm2. Autophagy was evaluated by immunocytochemistry
using specific antibodies to Atg7, Beclin-1 and LC3. The evaluation was repeated
at several time points (0, 4, 8 and 24 h) following irradiation. The induction of
autophagy was observed directly following the 5-ALA-mediated PDT procedure with
the strongest expression of autophagy-related proteins at 4 and 8 h after
irradiation as demonstrated using immunocytochemistry. It was characterized by
significantly increased expression of Beclin-1, Atg7 and LC3. To the best of our
knowledge this is the first study to analyze Beclin-1, Atg7 and LC3 expression in
a PDT-related experiment. This study enhances the understanding of the role of
autophagy in PDT, which may contribute to better and more effective tumor
responses to this therapy.
PMID- 27485941
TI - Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity.
AB - OBJECTIVES: PRIMARY OBJECTIVE: To retrospectively review nafcillin plasma
concentrations (CNAF ) and determine nafcillin clearance (CLNAF ) in a diverse
sample of patients treated with nafcillin administered as a continuous infusion.
SECONDARY OBJECTIVE: To identify clinical variables associated with CLNAF and
nafcillin-related adverse drug reactions (ADRs). METHODS: Retrospective chart
review of patients receiving nafcillin via continuous infusion at University of
Utah Health Care from 2006 to 2013 who had at least one steady-state CNAF
measured. CLNAF was determined by dividing the nafcillin rate of infusion by CNAF
. Adverse drug reactions (ADRs) were defined using the National Institutes of
Health, Division of Microbiology and Infectious Diseases criteria and scored for
probability of association with nafcillin by using Naranjo criteria. Multivariate
models were constructed to identify independent variables associated with CLNAF
and ADRs. MAIN RESULTS: Seventy-six CNAF from 54 patients were included. Median
CLNAF was 13.9 L/hour (range <= 4.2 to 36.9 L/hr). Congestive heart failure
(p=0.007), hyperbilirubinemia (p<0.0001), and serum creatinine (p<0.0001) were
associated with reduced CLNAF , and Hispanic race (p=0.002) was associated with
increased CLNAF by multivariate analysis. Twenty patients (37.0%) experienced an
ADR. CNAF were significantly higher between patients that experienced an ADR and
those that did not (66.0 vs 25.5 mg/L, p<0.001). Individual ADRs associated with
CNAF included hepatotoxicity (62.8 vs 27.0 mg/L, p=0.001), nausea/vomiting (80.0
vs 28.5 mg/L, p=0.01), and diarrhea (66.5 vs 26.5 mg/L, p<0.001). Multivariate
analysis identified CNAF as being independently associated with ADRs. A putative
toxicity relationship between CNAF and predicted probability of ADR was
established. CONCLUSIONS: Several patient variables were associated with impaired
CLNAF , and elevated CNAF were associated with ADRs. Additional studies assessing
the utility of nafcillin therapeutic drug monitoring to minimize toxicity are
warranted.
PMID- 27485942
TI - A Study of Hmong Immigrants' Experience With Diabetes Education: A Community
Engaged Qualitative Study.
AB - PURPOSE: The prevalence of diabetes is increasing in Hmong Americans, an
understudied ethnic minority group. This research sought to identify barriers and
facilitators related to the diabetes education experience of Hmong Americans with
type 2 diabetes, living in central California. METHOD: This qualitative study
employed a hybrid design to identify barriers and facilitators to diabetes
education. Two focus group interviews were conducted among 16 participants.
FINDINGS: The three barriers identified are language, self-management, and
stress; the three facilitators are focused culturally specific education, use of
media, and peer support group. A priori elements of the Study of Access framework
were confirmed. DISCUSSION/CONCLUSION: There is a need for diabetes education in
Hmong Americans. Health care access and education should incorporate culturally
appropriate strategies that could improve health outcomes for the Hmong.
IMPLICATION: To improve diabetes care in the Hmong population, health educators
should consider the use of cultural competency, language assistance, and
culturally appropriate education to achieve better clinical outcomes.
PMID- 27485944
TI - Impact of Infection on Stroke Morbidity and Outcomes.
AB - Each year, millions of persons worldwide are disabled by stroke. The burden of
stroke is expected to increase as a consequence of growth in our elderly
population. Outcome is dependent upon limitation of secondary medical processes
in the acute setting that lead to deterioration and increased long-term
disability. The prevalence of infection after stroke is greater that seen in
other medical conditions with similar acuity and its impact upon morbidity and
mortality is substantial. Physical impairment and immune modulation are chief
determinants in rate of infection after stroke. Each of these factors has been a
target for therapeutic intervention. Current best practices for acute stroke
management implement strategies for prevention, prompt identification, and
treatment of infection. Novel therapies are currently being explored which have
the opportunity to greatly minimize infectious complications following stroke.
Fever commonly accompanies infection and independently influences stroke outcome.
Targeted temperature management provides an additional chance to improve stroke
recovery.
PMID- 27485943
TI - Multiprotein-bridging factor 1 regulates vegetative growth, osmotic stress, and
virulence in Magnaporthe oryzae.
AB - Multiprotein bridging factor 1 (MBF1) is a transcriptional co-activator that
mediates transcriptional activation by bridging sequence-specific activator like
proteins and the TATA-box binding protein (TBP). MBF1 has been well-studied in
Arabidopsis thaliana, Saccharomyces cerevisiae, Drosophila melanogaster, and Homo
sapiens, but it is not well understood in filamentous fungi. In this study, we
report the identification and characterization of a MBF1 ortholog (MoMBF1) in the
rice blast fungus Magnaporthe oryzae), which causes the devastating rice blast
disease and is an ideal model for studying the growth, development and pathogenic
mechanisms of filamentous fungi. MoMBF1 encodes a 161 amino acid protein with a
typical MBF1 domain and HTH domain. Bioinformatics were used to analyze the
structural domains in MoMBF1 and its phylogenetic relationship to other homologs
from different organisms. We have generated MoMBF1 deletion mutants (DeltaMoMBF1)
and functional complementation transformants, and found that the deletion mutants
showed significant defects in vegetative growth and tolerance to exogenous
stresses, such as 1 M sorbitol, 0.5 M NaCl, and 5 mM H2O2. Moreover, DeltaMoMBF1
showed reduced pathogenicity with smaller infection lesions than wild type and
the complementation strain, and decreased response to the accumulation of ROS
(reactive oxygen species) in planta at the initial infection stage. Taken
together, our data indicate that MoMBF1 is required for vegetative growth,
pathogenicity and stress response in M. oryzae.
PMID- 27485945
TI - Alemtuzumab for Multiple Sclerosis.
AB - Alemtuzumab is a humanised anti-CD52 monoclonal antibody approved for use in
active, relapsing multiple sclerosis (MS). Administration results in a rapid
depletion of circulating lymphocytes with a subsequent beneficial immune
reconstitution. Early open-label experience and recent clinical trials have
demonstrated a dramatic effect on relapse rates as well as a positive effect on
radiological disease outcomes and disability measures. Despite a mechanism of
action that results in profound lymphopaenia, opportunistic infections are rarely
seen and no excess association with malignancy has been identified. However,
acquired autoimmune disease (AID) is a common adverse event following treatment,
necessitating rigorous monitoring in order to facilitate prompt detection and
management. Despite this issue, a unique dosing schedule and durability of effect
make alemtuzumab a welcome addition to currently available treatment options for
MS.
PMID- 27485947
TI - Geometric morphometrics reveals restrictions on the shape of the female os coxae.
AB - The methodology for sex determination in human skeletal remains depends on the
different bone morphologies presented by men and women. Due to their direct
implications in reproduction, the whole pelvis, particularly the os coxae, shows
different characteristics in either sex. The sacrum and the os coxae constitute
the birth canal. In this research study, the os coxae shape is analyzed using
geometric morphometrics, providing information on morphology, regardless of size
or any other factor beyond the geometry itself. A total of 46 adult ossa coxae
from a Spanish archaeological collection were studied using geometric
morphometrics. The results show that there is a restriction on the shape of
female os coxae. In contrast, male os coxae presents a greater range of
variation. The biological reason for this difference is the obstetrical dilemma;
a concept defined as the anatomical conflict between bipedalism and the full-term
birth of a neonate whose large head requires greater dimensions in the pelvic
cavity. Our experimental data reinforce the validity of the obstetrical dilemma
as source of the restriction on the shape of female ossa coxae. Additionally,
according to the results obtained, size itself does not represent a condition for
belonging to one sex or another.
PMID- 27485946
TI - Sleep Disturbances in Frontotemporal Dementia.
AB - Sleep disorders appear to be frequent comorbidities in patients with
frontotemporal dementia (FTD). Insomnia and excessive daytime sleepiness commonly
occur in patients with FTD and significantly contribute to caregiver burden and
burnout. Sleep is severely fragmented in FTD patients, likely secondary to
behavioral disturbances, other primary sleep disorders such as sleep disordered
breathing and restless leg syndrome, and neurodegeneration of nuclei involved in
sleep and wakefulness. Treatment of primary sleep disorders may improve excessive
daytime sleepiness and sleep quality and may improve daytime cognitive
functioning. Rapid eye movement (REM) sleep behavior disorder is rare in FTD and
may be confused with excessive nocturnal activity due to disturbed circadian
rhythm. The relationship between FTD, sleep quality, and sleep disorders requires
further study to better understand the contribution of disturbed sleep to daytime
neurocognitive functioning and quality of life in FTD. Further, future studies
should focus on comparing sleep disturbances between different FTD syndromes,
especially behavioral variant FTD and primary progressive aphasia. Comorbid sleep
disorders should be promptly sought and treated in patients with FTD to improve
patient and caregiver quality of life.
PMID- 27485948
TI - Challenges in the development of novel anticryptococcal agents.
PMID- 27485949
TI - Properties of Life: Toward a Coherent Understanding of the Organism.
AB - The question of specific properties of life compared to nonliving things
accompanied biology throughout its history. At times this question generated
major controversies with largely diverging opinions. Basically, mechanistic
thinkers, who tried to understand organismic functions in terms of nonliving
machines, were opposed by those who tried to describe specific properties or even
special forces being active within living entities. As this question included the
human body, these controversies always have been of special relevance to our self
image and also touched practical issues of medicine. During the second half of
the twentieth century, it seemed to be resolved that organisms are explainable
basically as physicochemical machines. Especially from the perspective of
molecular biology, it seemed to be clear that organisms need to be explained
solely by the chemical functions of their component parts, although some
resistance to this view never ceased. This research program has been working
quite successfully, so that science today knows a lot about the physiological and
chemical processes within organisms. However, again new doubts arise questioning
whether the mere continuation of this analytical approach will finally generate a
fundamental understanding of living entities. At the beginning of the twenty
first century the quest for a new synthesis actually comes from analytical
empiricists themselves. The hypothesis of the present paper is that empirical
research has been developed far enough today, that it reveals by itself the
materials and the prerequisites to understand more of the specific properties of
life. Without recourse to mysterious forces, it is possible to generate answers
to this age-old question, just using recent, empirically generated knowledge.
This view does not contradict the results of reductionistic research, but rather
grants them meaning within the context of organismic systems and also may
increase their practical usefulness. Although several of these properties have
been discussed before, different authors usually concentrated on a single one or
some of them. The paper describes ten specific properties of living entities as
they can be deduced from contemporary science. The aim is to demonstrate that the
results of empirical research show both the necessity as well as the possibility
of the development of a new conception of life to build a coherent understanding
of organismic functions.
PMID- 27485950
TI - Memory deficits with intact cognitive control in the methylazoxymethanol acetate
(MAM) exposure model of neurodevelopmental insult.
AB - Cognitive impairments are amongst the most debilitating deficits of schizophrenia
and the best predictor of functional outcome. Schizophrenia is hypothesized to
have a neurodevelopmental origin, making animal models of neurodevelopmental
insult important for testing predictions that early insults will impair cognitive
function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17
display morphological, physiological and behavioral abnormalities relevant to
schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We
examined brain activity in MAM rats by histochemically assessing cytochrome
oxidase enzyme activity, a metabolic marker of neuronal activity. To assess
cognition, we used a hippocampus-dependent two-frame active place avoidance
paradigm to examine learning and spatial memory, as well as cognitive control and
flexibility using the same environment and evaluating the same set of behaviors.
We confirmed that adult MAM rats have altered hippocampal morphology and brain
function, and that they are hyperactive in an open field. The latter likely
indicates MAM rats have a sensorimotor gating deficit that is common to many
animal models used for schizophrenia research. On first inspection, cognitive
control seems impaired in MAM rats, indicated by more errors during the two-frame
active place avoidance task. Because MAM rats are hyperactive throughout place
avoidance training, we considered the possibility that the hyperlocomotion may
account for the apparent cognitive deficits. These deficits were reduced on the
basis of measures of cognitive performance that account for motor activity
differences. However, though other aspects of memory are intact, the ability of
MAM rats to express trial-to-trial memory is delayed compared to control rats.
These findings suggest that spatial learning and cognitive abilities are largely
intact, that the most prominent cognitive deficit is specific to acquiring memory
in the MAM neurodevelopmental model, and that hyperactivity can confound
assessments of cognition in animal models of mental dysfunction.
PMID- 27485951
TI - Floating lumbar spine: proposed mechanism with review of literature.
AB - Hyperextension injuries of lumbar spine resulting in lumbosacral dislocation are
a rare entity. We report a case of a 60-year-old male who presented to us in
outpatient department with history of trivial fall from bicycle with fracture
through the pedicles extending from L2 to L5 with lumbosacral dislocation with
free floating posterior elements with intact neurology. This is the first case
report of 4 level extension compression injury with lumbosacral dislocation
leading to floating lumbar spine to the best of author's knowledge. Treatment
consists of reduction of the lumbosacral dislocation first and fusion of the disc
space followed by reduction of the other fractures proximally. These injuries may
present with a trivial trauma in spondylotic spine in elderly patients. MRI and
CT scan should be done early to identify it, reduce and fix it, as in many cases
with trivial trauma there may be no neural deficit.
PMID- 27485953
TI - In situ thiolated alginate hydrogel: Instant formation and its application in
hemostasis.
AB - An in situ formed hydrogel was synthesized by sodium alginate and cysteine methyl
ester, which turned the sodium alginate into thiolated alginate (SA-SH). SA-SH
can in situ formed into hydrogel (SA-SS-SA) with a large amount of water through
covalent bond in less than 20 s. The structure characterization showed that the
mechanism of SA-SH gelation was thiol-disulfide transformation. The rheology and
cytotoxicity experiments of SA-SS-SA hydrogel were also investigated, which
indicated that SA-SS-SA hydrogel had an appropriate mechanical strength as well
as an excellent biocompatibility. The SA-SS-SA hydrogel would degrade under
certain conditions after a few days and its mechanism was disulfide alkaline
reduction. Finally, the hemostatic property of SA-SH was tested by rat tail
amputation experiment. The time to hemostasis of rat reduced from 8.26 min to
3.24 min, which proved that SA-SH had an excellent hemostatic property.
PMID- 27485954
TI - Mechanical properties, biological behaviour and drug release capability of nano
TiO2-HAp-Alginate composite scaffolds for potential application as bone implant
material.
AB - Nanocomposite scaffolds of TiO2 and hydroxyapatite nanoparticles with alginate as
the binding agent were fabricated using the freeze drying technique. TiO2,
hydroxyapatite and alginate were used in the ratio of 1:1:4. The scaffolds were
characterized using X-ray diffraction, fourier transform infrared spectroscopy,
and scanning electron microscopy. The biocompatibility of the scaffolds was
evaluated using cell adhesion and MTT assay on osteosarcoma (MG-63) cells.
Scanning electron microscopy analysis revealed that cells adhered to the surface
of the scaffolds with good spreading. The mechanical properties of the scaffolds
were investigated using dynamic mechanical analysis. The swelling ability,
porosity, in vitro degradation, and biomineralization of the scaffolds were also
evaluated. The results indicated controlled swelling, limited degradation, and
enhanced biomineralization. Further, drug delivery studies of the scaffolds using
the chemotherapeutic drug methotrexate exhibited an ideal drug release profile.
These scaffolds are proposed as potential candidates for bone tissue engineering
and drug delivery applications.
PMID- 27485955
TI - Persistent maternal Zika viremia: a marker of fetal infection.
PMID- 27485969
TI - Analysis of Gambierdiscus transcriptome data supports ancient origins of
mixotrophic pathways in dinoflagellates.
AB - Toxic dinoflagellates pose serious threats to human health and to fisheries. The
genus Gambierdiscus is significant in this respect because its members produce
ciguatoxin that accumulates in predominantly tropical marine food webs and leads
to ciguatera fish poisoning. Understanding the biology of toxic dinoflagellates
is crucial to developing control strategies. To this end, we generated a de novo
transcriptome library from G. caribaeus and studied its growth under different
culture conditions to elucidate pathways of carbon (C) and nitrogen (N)
utilization. We also gathered available dinoflagellate transcriptome data to
trace the evolutionary history of C and N pathways in this phylum. We find that
rather than being specific adaptations to the epiphytic lifestyle in G.
caribaeus, the majority of dinoflagellates share a large array of genes that
putatively confer mixotrophy and the ability to use N via the ornithine-urea
cycle and nitric oxide synthase production. These results suggest that prior to
plastid endosymbiosis, the dinoflagellate ancestor possessed complex pathways
that linked metabolism, intercellular signaling, and stress responses to
environmental cues that have been maintained by extant photosynthetic species.
This metabolic flexibility likely explains the success of dinoflagellates in
marine ecosystems and may presage difficulties in controlling the spread of toxic
species.
PMID- 27485952
TI - Consensus Paper: Cerebellum and Emotion.
AB - Over the past three decades, insights into the role of the cerebellum in
emotional processing have substantially increased. Indeed, methodological
refinements in cerebellar lesion studies and major technological advancements in
the field of neuroscience are in particular responsible to an exponential growth
of knowledge on the topic. It is timely to review the available data and to
critically evaluate the current status of the role of the cerebellum in emotion
and related domains. The main aim of this article is to present an overview of
current facts and ongoing debates relating to clinical, neuroimaging, and
neurophysiological findings on the role of the cerebellum in key aspects of
emotion. Experts in the field of cerebellar research discuss the range of
cerebellar contributions to emotion in nine topics. Topics include the role of
the cerebellum in perception and recognition, forwarding and encoding of
emotional information, and the experience and regulation of emotional states in
relation to motor, cognitive, and social behaviors. In addition, perspectives
including cerebellar involvement in emotional learning, pain, emotional aspects
of speech, and neuropsychiatric aspects of the cerebellum in mood disorders are
briefly discussed. Results of this consensus paper illustrate how theory and
empirical research have converged to produce a composite picture of brain
topography, physiology, and function that establishes the role of the cerebellum
in many aspects of emotional processing.
PMID- 27485970
TI - Psychometric Validation of the Parental Bonding Instrument in a U.K. Population
Based Sample: Role of Gender and Association With Mental Health in Mid-Late Life.
AB - The factorial structure of the Parental Bonding Instrument (PBI) has been
frequently studied in diverse samples but no study has examined its psychometric
properties from large, population-based samples. In particular, important
questions have not been addressed such as the measurement invariance properties
across parental and offspring gender. We evaluated the PBI based on responses
from a large, representative population-based sample, using an exploratory
structural equation modeling method appropriate for categorical data. Analysis
revealed a three-factor structure representing "care," "overprotection," and
"autonomy" parenting styles. In terms of psychometric measurement validity, our
results supported the complete invariance of the PBI ratings across sons and
daughters for their mothers and fathers. The PBI ratings were also robust in
relation to personality and mental health status. In terms of predictive value,
paternal care showed a protective effect on mental health at age 43 in sons. The
PBI is a sound instrument for capturing perceived parenting styles, and is
predictive of mental health in middle adulthood.
PMID- 27485971
TI - Comment on "Cellular and molecular aspects of diabetic nephropathy; the role of
VEGF-A".
PMID- 27485972
TI - Treating refractory mental illness with closed-loop brain stimulation: Progress
towards a patient-specific transdiagnostic approach.
AB - Mental disorders are a leading cause of disability, morbidity, and mortality
among civilian and military populations. Most available treatments have limited
efficacy, particularly in disorders where symptoms vary over relatively short
time scales. Targeted modulation of neural circuits, particularly through open
loop deep brain stimulation (DBS), showed initial promise but has failed in
blinded clinical trials. We propose a new approach, based on targeting neural
circuits linked to functional domains that cut across diagnoses. Through that
framework, which includes measurement of patients using six psychophysical tasks,
we seek to develop a closed-loop DBS system that corrects dysfunctional activity
in brain circuits underlying those domains. We present convergent preliminary
evidence from functional neuroimaging, invasive human electrophysiology, and
human brain stimulation experiments suggesting that this approach is feasible.
Using the Emotional Conflict Resolution (ECR) task as an example, we show that
emotion-related networks can be identified and modulated in individual patients.
Invasive and non-invasive methodologies both identify a network between
prefrontal cortex, cingulate cortex, insula, and amygdala. Further, stimulation
in cingulate and amygdala changes patients' performance in ways that are linked
to the task's emotional content. We present preliminary statistical models that
predict this change and allow us to track it at a single-trial level. As these
diagnostic and modeling strategies are refined and embodied in an implantable
device, they offer the prospect of a new approach to psychiatric treatment and
its accompanying neuroscience.
PMID- 27485973
TI - Role of extracellular matrix protein CabA in resistance of Vibrio vulnificus
biofilms to decontamination strategies.
AB - Biofilms are recalcitrant and raise safety problems in the food industry. In this
study, the role of CabA, an extracellular matrix protein, in the resistance of
the biofilms of Vibrio vulnificus, a foodborne pathogen, to decontamination
strategies was investigated. Biofilms of the cabA mutant revealed reduced
resistance to detachment by vibration and disinfection by sodium hypochlorite
compared to the biofilms of the parental wild type in vitro. The reduced
resistance of the cabA mutant biofilms was complemented by introducing a
recombinant cabA, indicating that the reduced resistance of the cabA mutant
biofilms is caused by the inactivation of cabA. The expression of cabA was
induced in cells bound to oyster, the primary vehicle of the pathogen. The cabA
mutant biofilms on oyster are defective in biomass and resistance to detachment
and disinfection. The bacterial cells in the wild-type biofilms are clustered by
filaments which are not apparent in the cabA mutant biofilms. The combined
results indicated that CabA contributes to the structural integrity of V.
vulnificus biofilms possibly by forming filaments in the matrix and thus
rendering the biofilms robust, suggesting that CabA could be a target to control
V. vulnificus biofilms on oyster.
PMID- 27485976
TI - A Summer School for Structuring the Chemoinformatics Community.
PMID- 27485974
TI - A novel approach to study the structure-property relationships and applications
in living systems of modular Cu(2+) fluorescent probes.
AB - A series of Cu(2+) probe which contains 9 probes have been synthesized and
established. All the probes were synthesized using Rhodamine B as the
fluorophore, conjugated to various differently substituted cinnamyl aldehyde with
C=N Schiff base structural motif as their core moiety. The structure-property
relationships of these probes have been investigated. The change of optical
properties, caused by different electronic effect and steric effect of the
recognition group, has been analyzed systematically. DFT calculation simulation
of the Ring-Close and Ring-Open form of all the probes have been employed to
illuminate, summarize and confirm these correlations between optical properties
and molecular structures. In addition, biological experiment demonstrated that
all the probes have a high potential for both sensitive and selective detection,
mapping of adsorbed Cu(2+) both in vivo and environmental microbial systems. This
approach provides a significant strategy for studying structure-property
relationships and guiding the synthesis of probes with various optical
properties.
PMID- 27485975
TI - Protein-Anchoring Therapy of Biglycan for Mdx Mouse Model of Duchenne Muscular
Dystrophy.
AB - Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by loss
of-function mutations in DMD encoding dystrophin. No rational therapy is
currently available. Utrophin is a paralog of dystrophin and is highly expressed
at the neuromuscular junction. In mdx mice, utrophin is naturally upregulated
throughout the muscle fibers, which mitigates muscular dystrophy. Protein
anchoring therapy was previously reported, in which a recombinant extracellular
matrix (ECM) protein is delivered to and anchored to a specific target using its
proprietary binding domains. Being prompted by a report that intramuscular and
intraperitoneal injection of an ECM protein, biglycan, upregulates expression of
utrophin and ameliorates muscle pathology in mdx mice, protein-anchoring therapy
was applied to mdx mice. Recombinant adeno-associated virus serotype 8 (rAAV8)
carrying hBGN encoding human biglycan was intravenously injected into 5-week-old
mdx mice. The rAAV8-hBGN treatment improved motor deficits and decreased plasma
creatine kinase activities. In muscle sections of treated mice, the number of
central myonuclei and the distribution of myofiber sizes were improved. The
treated mice increased gene expressions of utrophin and beta1-syntrophin, as well
as protein expressions of biglycan, utrophin, gamma-sarcoglycan, dystrobrevin,
and alpha1-syntrophin. The expression of hBGN in the skeletal muscle of the
treated mice was 1.34-fold higher than that of the native mouse Bgn (mBgn). The
low transduction efficiency and improved motor functions suggest that biglycan
expressed in a small number of muscle fibers was likely to have been secreted and
anchored to the cell surface throughout the whole muscular fibers. It is proposed
that the protein-anchoring strategy can be applied not only to deficiency of an
ECM protein as previously reported, but also to augmentation of a naturally
induced ECM protein.
PMID- 27485977
TI - Future De Novo Drug Design.
AB - The computer-assisted generation of new chemical entities (NCEs) has matured into
solid technology supporting early drug discovery. Both ligand- and receptor-based
methods are increasingly used for designing small lead- and druglike molecules
with anticipated multi-target activities. Advanced "polypharmacology" prediction
tools are essential pillars of these endeavors. In addition, it has been realized
that iterative design-synthesis-test cycles facilitate the rapid identification
of NCEs with the desired activity profile. Lab-on-a-chip platforms integrating
synthesis, analytics and bioactivity determination and controlled by adaptive,
chemistry-driven de novo design software will play an important role for future
drug discovery.
PMID- 27485978
TI - The Calculation of Molecular Structural Similarity: Principles and Practice.
AB - Measures of structural similarity play an important role in chemoinformatics for
applications such as similarity searching, database clustering and molecular
diversity analysis. A similarity measure comprises three components: a structure
representation; a weighting scheme; and a similarity coefficient. The paper
introduces these components and describes methods for comparing different
measures. The use of similarity measures in chemoinformatics research is
illustrated by recent projects in the author's laboratory on: the interactions
between a weighting scheme and a similarity coefficient; the design of
comparative studies of similarity measures; the use of 2D fingerprints for
scaffold-hopping searches; and the registration of orphan drugs for rare
diseases.
PMID- 27485979
TI - Exploring Activity Cliffs from a Chemoinformatics Perspective.
AB - The activity cliff concept experiences considerable interest in medicinal
chemistry and chemoinformatics. Activity cliffs are defined as pairs or groups of
structurally similar or analogous active compounds having large differences in
potency. Depending on the research field, views of activity cliffs partly differ.
While interpretability and utility of activity cliff information is considered to
be of critical importance in medicinal chemistry, large-scale exploration and
prediction of activity cliffs are of special interest in chemoinformatics. Much
emphasis has recently been put on making activity cliff information accessible
for medicinal chemistry applications. Herein, different approaches to the
analysis and prediction of activity cliffs are discussed that are of particular
relevance from a chemoinformatics viewpoint.
PMID- 27485980
TI - Investigating and Predicting how Biology Changes Molecules and Their Properties.
AB - Most molecules are transformed and transported by specific metabolising enzymes
and transporters resulting in changes in their bioactivities, pharmacokinetics
and toxicity profiles. This is a key consideration in the design of drugs.
Ideally, when medicines have performed their task, they need to fade away
gracefully, and not introduce unexpected or untoward biological effects. Some
examples of predictive metabolism, transport and interesting design
considerations of drugs are described.
PMID- 27485981
TI - BioGPS: The Music for the Chemo- and Bioinformatics Walzer.
AB - Identifying cross-relationships among protein binding sites is becoming
increasingly important in the chemo- and bioinformatics field; indeed, protein
structural similarity might provide the right answer to a number of questions
including Is a drug repurposable for another target? What is the molecular
mechanism of a drug side-effect? How can we improve the ligand selectivity? The
comparison of protein binding sites in terms of their three-dimensional structure
molecular interaction fields can be a useful technique to approach all of these
problems. Here, we report a semi-automated method for comparing and clustering
protein pockets, called BioGPS, that combines the GRID Molecular Interactions
Fields (MIFs) with FLAP pharmacophoric fingerprints. BioGPS identifies and
compares protein binding sites by aligning them each other and directly comparing
their MIFs. The strengths of this approach are that it is MIF-based, and
therefore describes molecular interactions from a ligand perspective, and it is
independent of protein superposition or sequence alignment. This approach enables
protein-protein virtual screening (drug repurposing, polypharmacology, off-target
effects), and also clustering to relate sequence-based similarities to structure
based differences among protein binding sites.
PMID- 27485982
TI - Solved and Unsolved Problems of Chemoinformatics.
AB - From humble beginnings in the Sixties chemoinformatics evolved into a scientific
field of its own. Without the achievements of chemoinformatics the flood of
information in chemistry would simply not be manageable and modern research in
chemistry and related fields would be inconceivable. However, there are still a
host of problems waiting for solutions to be found or to be improved. The impact
of chemicals on human health and on the environment presents both challenges and
concerns. Research in chemoinformatics could help in better understanding these
topics and thus contribute to a better living.
PMID- 27485983
TI - Bioisosteres and Scaffold Hopping in Medicinal Chemistry.
AB - The twin concepts of bioisosteric replacement and scaffold hopping are
increasingly becoming important in modern drug design. The concepts of isosterism
stretch back over a century, but only recently have systematic and data-intensive
methods been used to explore appropriate replacements. Here, a summary of the
history of bioisosterism is presented to provide context to the methods applied.
Molecular similarity and data mining methods are introduced as approaches to
introduce these replacements to rationalise the space of synthetic targets to
consider in a medicinal chemistry project. Lastly, an outlook of the field is
given of potential future improvements and areas of focus that should be
considered to anyone interested in the field.
PMID- 27485984
TI - Attractor Structures of Signaling Networks: Consequences of Different
Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.
AB - Conformational barcodes tag functional sites of proteins and are decoded by
interacting molecules transmitting the incoming signal. Conformational barcodes
are modified by all co-occurring allosteric events induced by post-translational
modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity)
of conformational barcodes may be increased by disordered protein structures, by
integrative plasticity of multi-phosphorylation events, by increased
intracellular water content (decreased molecular crowding) and by increased
action of molecular chaperones. This leads to increased plasticity of signaling
and cellular networks. Increased plasticity is both substantiated by and inducing
an increased noise level. Using the versatile network dynamics tool, Turbine
(www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in
cellular systems shifts a cancer-related signaling network of human cells from
its proliferative attractors to its largest, apoptotic attractor representing
their health-preserving response in the carcinogen containing and tumor
suppressor deficient environment modeled in our study. Thus, fuzzy conformational
barcodes may not only make the cellular system more plastic, and therefore more
adaptable, but may also stabilize the complex system allowing better access to
its largest attractor.
PMID- 27485985
TI - A Short Review of Chemical Reaction Database Systems, Computer-Aided Synthesis
Design, Reaction Prediction and Synthetic Feasibility.
AB - This article is the text for a pedagogical lecture to be given at the Strasbourg
Summer School in Chemoinformatics in June 2104. It covers a very wide range of
reaction topics including structure and reaction representation, reaction
centers, atom-to-atom mapping, reaction retrieval systems, computer-aided
synthesis design, retrosynthesis, reaction prediction and synthetic feasibility.
In the time available the coverage of each topic can only be cursory; the main
usefulness of this article to the research community is the extensive
bibliography.
PMID- 27485986
TI - Individual Hydrogen-Bond Strength QSPR Modelling with ISIDA Local Descriptors: a
Step Towards Polyfunctional Molecules.
AB - Here, we introduce new ISIDA fragment descriptors able to describe "local"
properties related to selected atoms or molecular fragments. These descriptors
have been applied for QSPR modelling of the H-bond basicity scale pKBHX ,
measured by the 1 : 1 complexation constant of a series of organic acceptors (H
bond bases) with 4-fluorophenol as the reference H-bond donor in CCl4 at 298 K.
Unlike previous QSPR studies of H-bond complexation, the models based on these
new descriptors are able to predict the H-bond basicity of different acceptor
centres on the same polyfunctional molecule. QSPR models were obtained using
support vector machine and ensemble multiple linear regression methods on a set
of 537 organic compounds including 5 bifunctional molecules. They were validated
with cross-validation procedures and with two external test sets. The best model
displays good predictive performance on a large test set of 451 mono- and
bifunctional molecules: a root-mean squared error RMSE=0.26 and a determination
coefficient R(2) =0.91. It is implemented on our website (http://infochim.u
strasbg.fr/webserv/VSEngine.html) together with the estimation of its
applicability domain and an automatic detection of potential H-bond acceptors.
PMID- 27485988
TI - An experimental and theoretical study of the aggregate structure of
calix[6]arenes in Langmuir films at the water/air interface.
AB - In this paper, the aggregate formation of para-tert-butylcalix[6]arene molecules
(Calix6) in dimeric structures was investigated at the water/air interface using
experimental and theoretical studies. A specific orientation for such Calix6
molecules was observed with an average area of 133 A(2), which corresponds to a
flat-on orientation with the OH groups parallel to the interface. By varying the
pressure on the Calix6 monolayer, the molecules tend to organize at the water/air
interface and subsequently, at higher pressures, aggregates were formed atop the
monolayer as cluster structures. Morphological characterization by the Brewster
Angle Microscopy technique showed the formation of larger domains at lower
pressures. Based on such experimental evidence, molecular dynamics (MD)
simulations were performed to investigate possible dimeric structures for
aggregated Calix6 molecules, which are localized at the water/air interface,
where one molecule remains in the water phase and the other remains in the air
phase. By increasing surface pressure, experimental and theoretical results
corroborate the intermolecular interactions among Calix6 molecules. These results
are relevant because a dimeric structure has a molecular cavity, which is a
candidate for host-guest chemistry, an ion receptor or a drug-delivery system.
PMID- 27485987
TI - Substance Use among a Sample of Healthcare Workers in Kenya: A Cross-Sectional
Study.
AB - This study describes reported substance use among Kenyan healthcare workers
(HCWs), as it has implications for HCWs' health, productivity, and their ability
and likelihood to intervene on substance use. The Alcohol Smoking and Substance
Involvement Screening Test (ASSIST) was administered to a convenience sample of
HCWs (n = 206) in 15 health facilities. Reported lifetime use was 35.8% for
alcohol, 23.5% for tobacco, 9.3% for cannabis, 9.3% for sedatives, 8.8% for
cocaine, 6.4% for amphetamine-like stimulants, 5.4% for hallucinogens, 3.4% for
inhalants, and 3.9% for opioids. Tobacco and alcohol were also the two most
commonly used substances in the previous three months. Male gender and other
substance use were key predictors of both lifetime and previous three months' use
rates. HCWs' substance use rates appear generally higher than those seen in the
general population in Kenya, though lower than those reported among many HCWs
globally. This pattern of use has implications for both HCWs and their clients.
PMID- 27485989
TI - Confronting the Problem of Obesity in Dogs and Cats.
PMID- 27485990
TI - Can dispersion modeling of air pollution be improved by land-use regression? An
example from Stockholm, Sweden.
AB - Both dispersion modeling (DM) and land-use regression modeling (LUR) are often
used for assessment of long-term air pollution exposure in epidemiological
studies, but seldom in combination. We developed a hybrid DM-LUR model using 93
biweekly observations of NOx at 31 sites in greater Stockholm (Sweden). The DM
was based on spatially resolved topographic, physiographic and emission data, and
hourly meteorological data from a diagnostic wind model. Other data were from
land use, meteorology and routine monitoring of NOx. We built a linear regression
model for NOx, using a stepwise forward selection of covariates. The resulting
model predicted observed NOx (R2=0.89) better than the DM without covariates
(R2=0.68, P-interaction <0.001) and with minimal apparent bias. The model
included (in descending order of importance) DM, traffic intensity on the nearest
street, population (number of inhabitants) within 100 m radius, global radiation
(direct sunlight plus diffuse or scattered light) and urban contribution to NOx
levels (routine urban NOx, less routine rural NOx). Our results indicate that
there is a potential for improving estimates of air pollutant concentrations
based on DM, by incorporating further spatial characteristics of the immediate
surroundings, possibly accounting for imperfections in the emission data.
PMID- 27485991
TI - Non-smoking pregnant women and their fetuses are exposed to environmental tobacco
smoke as a result of living in multiunit housing.
AB - This study investigates whether pregnant women and their fetuses are exposed to
environmental tobacco smoke (ETS) as a result of living in apartments. We
measured cotinine concentrations in serum, a biomarker of exposure to ETS, in non
smoking women's umbilical cord blood collected at delivery and in maternal blood
drawn shortly after delivering a baby. Concurrently, information was collected
regarding the women's housing situation, whether family members or co-workers
smoked, and other potential exposure factors. Newborns whose non-smoking mothers
lived in an apartment during pregnancy were more than three times (OR 3.17, 95%
CI 1.62-6.21) more likely to have detectable levels of cotinine in their cord
blood serum than babies whose mothers lived in a detached house. There is a
strong association between detectable concentrations of cotinine in cord blood
serum and living in an apartment, even after adjusting for confounders, such as
exposure at home or at work. A similar association was observed between the
detectable levels of cotinine in maternal serum and living in an apartment (OR
1.95, 95% CI 1.03-3.71).
PMID- 27485993
TI - Effects of damping and stiffness of AFM cantilever on the imaging of fine
surfaces.
AB - In this paper, by applying the differential quadrature (DQ) method, a semi
analytical model has been developed for atomic force microscope cantilever, and
then by using the interfacial forces between the cantilever tip and imaged
surfaces, a 2D model has been extracted for imaging nano-sized fine samples. By
employing the present model, several simple and standard samples have been
imaged, and finally the effects of the microcantilever's structural damping and
its stiffness on the imaging results have been investigated. It has been observed
that, through the control of damping, the quality of the acquired images is
considerably improved. It has also been shown that the self-softening and self
hardening properties of cantilever have serious effects on the obtained images.
The present model can be used to study the effects of different parameters on the
process of imaging small-scale samples. Also, as one of its most important
applications, this model can be used in common multiscale models for simulating
and predicting the effects of large and small fields on each other.
PMID- 27485992
TI - Exposure science in an age of rapidly changing climate: challenges and
opportunities.
AB - Climate change is anticipated to alter the production, use, release, and fate of
environmental chemicals, likely leading to increased uncertainty in exposure and
human health risk predictions. Exposure science provides a key connection between
changes in climate and associated health outcomes. The theme of the 2015 Annual
Meeting of the International Society of Exposure Science-Exposures in an Evolving
Environment-brought this issue to the fore. By directing attention to questions
that may affect society in profound ways, exposure scientists have an opportunity
to conduct "consequential science"-doing science that matters, using our tools
for the greater good and to answer key policy questions, and identifying causes
leading to implementation of solutions. Understanding the implications of
changing exposures on public health may be one of the most consequential areas of
study in which exposure scientists could currently be engaged. In this paper, we
use a series of case studies to identify exposure data gaps and research paths
that will enable us to capture the information necessary for understanding
climate change-related human exposures and consequent health impacts. We hope
that paper will focus attention on under-developed areas of exposure science that
will likely have broad implications for public health.
PMID- 27485995
TI - Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in
Rats.
AB - Several studies have shown the hepatoprotective effect of the consumption of
coffee and tea, which is mainly attributed to caffeine. Many experimental studies
have demonstrated this effect; however, these studies used high caffeine doses
that are not related to human consumption. The aim of this study was to evaluate
the hepatoprotective effect of low doses of caffeine on carbon tetrachloride
(CCl4)-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and
CAFF10) were evaluated in chronic liver damage induced by CCl4 (0.75 mL/kg) in
rats. CAFF treatment was administered once a day and CCl4 administration was
twice weekly for 10 weeks. Liver function tests (biochemical markers) and
functional (sleeping time) and histological (hematoxylin-eosin and Masson
trichrome stains) parameters were carried out at the end of damage treatment.
Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect
supported by a decrease of alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and alkaline phosphatase (AP) serum activities and
bilirubin serum levels compared with control and also restored serum albumin
levels and liver glutathione (GSH). Moreover, CAFF prevented CCl4-induced
prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and
cell death. Our results demonstrated that low doses of CAFF exert a
hepatoprotective effect against CCl4 -induced liver damage in rats.
PMID- 27485996
TI - Talking about sex, relationships and intimacy: new guidance and standards for
nurses and other health and social care professionals working with young people
with life-limiting and life-threatening conditions: Publication of Sexuality
Standards and Guidance for nurses and other health and social care professionals
working with life-limited young adults, care staff and their families (December
2015 and July 2016).
PMID- 27485994
TI - Dynamics and genetics of a disease-driven species decline to near extinction:
lessons for conservation.
AB - Amphibian chytridiomycosis has caused precipitous declines in hundreds of species
worldwide. By tracking mountain chicken (Leptodactylus fallax) populations
before, during and after the emergence of chytridiomycosis, we quantified the
real-time species level impacts of this disease. We report a range-wide species
decline amongst the fastest ever recorded, with a loss of over 85% of the
population in fewer than 18 months on Dominica and near extinction on Montserrat.
Genetic diversity declined in the wild, but emergency measures to establish a
captive assurance population captured a representative sample of genetic
diversity from Montserrat. If the Convention on Biological Diversity's targets
are to be met, it is important to evaluate the reasons why they appear
consistently unattainable. The emergence of chytridiomycosis in the mountain
chicken was predictable, but the decline could not be prevented. There is an
urgent need to build mitigation capacity where amphibians are at risk from
chytridiomycosis.
PMID- 27485997
TI - Cannabis Hyperemesis Syndrome in the Emergency Department: How Can a Specialized
Addiction Team Be Useful? A Pilot Study.
AB - BACKGROUND: Chronic cannabis users may experience cyclical episodes of nausea and
vomiting and learned behavior of hot bathing. This clinical condition, known as
cannabis hyperemesis syndrome, was first reported in 2004. OBJECTIVE: Our aim was
to promote early recognition of this syndrome in emergency departments (EDs) and
to increase referral to addiction specialists. METHODS: Cannabis abusers were
admitted to the ED for vomiting or abdominal pain from June 1, 2014 to January 1,
2015 and diagnosed with cannabis hyperemesis syndrome by a specialized addiction
team. Then, medical records were examined retrospectively. RESULTS: Seven young
adults were included. Their mean age was 24.7 years (range 17-39 years) and the
majority were men (male-to-female ratio 1.2). Biological and toxicological blood
samples were taken in all patients. Tetrahydrocannabinol blood level was measured
in 4 patients, with a mean blood concentration of 11.6 ng/mL. Radiographic
examination including abdominal computed tomography and brain imaging were
negative, as was upper endoscopy. Five patients compulsively took hot baths in an
attempt to decrease the symptoms. Treatment was symptomatic. Five patients have
started follow-up with the specialized addiction team. CONCLUSIONS: Cannabis
hyperemesis syndrome is still under-diagnosed 10 years after it was first
described. Physicians should be aware of this syndrome to avoid repeated
hospitalizations or esophageal complications. Greater awareness should lead to
prompt treatment and prevention of future recurrence through cannabis cessation.
Addiction specialists, as well as medical toxicologists, are experts in the
management of cannabis abusers and can help re-establish the role of medical care
in this population in collaboration with emergency physicians.
PMID- 27485998
TI - Evaluation of US prescription patterns: Are treatment guidelines for cancer
associated venous thromboembolism being followed?
AB - INTRODUCTION: Venous thromboembolism (VTE) is a common complication of cancer.
Clinical practice guidelines recommend low-molecular-weight heparin (LMWH) for
treatment of cancer-associated VTE, but it is unclear how frequently these are
followed. This study assessed anticoagulation treatment patterns for VTE in newly
diagnosed cancer patients in the United States. MATERIALS AND METHODS:
MarketScan(r) claims records of more than 80 million insured members between
January 1, 2009 and July 31, 2014 were retrospectively analyzed. Subjects were
included if they were 18years of age or older, and had a diagnosis of cancer (9
solid tumor types) and VTE. Data were included for LMWH, warfarin, and other
anticoagulants (fondaparinux and direct oral anticoagulants [DOACs]). Patients
with anticoagulant treatment prior to cancer diagnosis were excluded. RESULTS:
VTE developed in 6.2% of cancer patients (median, 181days after cancer
diagnosis). VTE rates were highest for pancreatic (17.5%) and lung (12.6%) cancer
and lowest for breast (4.2%) and prostate (4.1%) cancer. For patients for whom
outpatient prescription data were available, warfarin was most commonly used
(50.0%), followed by LMWH (40.0%) and other anticoagulants (10.0%). Over 6months,
13% of patients who initiated injectable anticoagulants remained on them compared
with 30% of those who initiated oral anticoagulants. More patients switched from
LMWH to warfarin and other anticoagulants (44%) versus those who switched from
warfarin (28%). CONCLUSIONS: Warfarin was the most utilized anticoagulant for
cancer-associated VTE despite guideline recommendations for LMWH. More patients
remained on oral versus injectable agents, which may be related to self-injection
burden and costs.
PMID- 27485999
TI - Reply to: Early mobilization in abdominal and thoracic surgery.
PMID- 27486000
TI - Application of an individualized operative strategy for wedge resection of
gastric gastrointestinal stromal tumors: Effectiveness for tumors in difficult
locations.
AB - BACKGROUND: There is some concern that wedge resection of gastric
gastrointestinal stromal tumors is not feasible in certain anatomic locations,
such as the cardia or antrum. We sought to review our experience with treatment
of gastric gastrointestinal stromal tumors with a particular focus on nonanatomic
wedge resections in these challenging locations. METHODS: Patients undergoing
resection of gastrointestinal stromal tumors from 2000-2014 at the Montreal
General Hospital were identified from a prospectively collected database, and
outcomes were tabulated. An individualized operative strategy was used to guide
resection based on tumor location, size, and characteristics. Disease-free
survival and overall survival analyzed using the Kaplan-Meier method. Data are
presented as median (range). RESULTS: We identified 59 patients who underwent
operative resection for gastric gastrointestinal stromal tumors. Tumor location
was fundus/body/greater curvature in 35 (59%) patients, lesser curvature in 8
(14%) patients, antrum in 8 (14%) patients, and cardia in 8 (14%) patients.
Median tumor size was 4.5 cm (1.4-25 cm). The majority of cardia and antral
lesions were removed with wedge resections (14/16, 87%). For cardial and antral
tumors, on-table gastroscopy was used to guide the operative approach and prevent
narrowing of the Gastroesophageal junction or pylorus in all patients undergoing
wedge resection. Negative pathologic margins were achieved in all patients. The 5
year disease-free survival was 91% and 5-year overall survival was 95%.
CONCLUSION: When selected appropriately, and under the guidance of on-table
gastroscopy, laparoscopic nonanatomic wedge resection can be performed
successfully in the majority of cases, even for gastrointestinal stromal tumors
near the GEJ or pylorus, with excellent oncologic outcomes.
PMID- 27486001
TI - Propensity scores for comparative effectiveness research: Finding the right
match.
PMID- 27486002
TI - Perioperative and oncologic outcomes of minimally invasive liver resection for
colorectal metastases: A case-control study of 130 patients.
AB - BACKGROUND: Our aim was to compare the perioperative and oncologic outcomes of
open liver resection and minimally invasive liver resection in the management of
colorectal liver metastases. METHODS: Patients who underwent minimally invasive
liver resection for colorectal liver metastases between January 2006 and June
2015 at a single center were identified and matched by extent of resection to
consecutive open liver resection patients from the same period. Clinicopathologic
characteristics, perioperative data, recurrence, and survival outcomes were
collected and analyzed based on intention-to-treat. RESULTS: Sixty-five patients
underwent minimally invasive liver resection during this period and were matched
to 65 consecutive open liver resection patients, with similar baseline
demographic, tumor, and chemotherapy parameters. Conversion to open occurred in 5
(7.7%) minimally invasive liver resection patients. R0 resection rates and
operative times were comparable, but the estimated blood loss was less in the
minimally invasive liver resection group (median 200 mL vs 400 mL, P < .001), as
were perioperative transfusion rates (4.6% vs 15.4%, P = .04). The duration of
stay was shorter after minimally invasive liver resection (median 4 days vs 6
days, P < .001), while major and minor complication rates were similar and no
perioperative mortality was recorded. At a median follow-up of 28 months, there
was no difference regarding disease-free (P = .90) or overall survival (P = .37).
CONCLUSION: In selected patients with colorectal liver metastases, minimally
invasive liver resection resulted in similar oncologic outcomes, with decreased
blood loss and shorter duration of stay compared to patients who underwent open
liver resection.
PMID- 27486004
TI - Discussion.
PMID- 27486003
TI - Differential access to care: The role of age, insurance, and income on
race/ethnicity-related disparities in adult perforated appendix admission rates.
AB - BACKGROUND: Differences in perforated appendix admission rates (PAAR) are an
ambulatory-sensitive measure of access to care. While pediatric studies report
disparities in PAAR, initial adult investigations suggest a lack of racial/ethnic
inequity. The objectives of this study were to (1) assess for risk-adjusted,
racial/ethnic differences in PAAR among adults on a national scale, (2) consider
the extent to which variations (or lack thereof) are explained by age, insurance,
and income, and (3) compare results within the United States population to a
national segment of the population who are completely insured. METHODS: According
to the Agency for Healthcare Research and Quality definition of PAAR, adults
(aged 18-64 years) in the 2006-2010 Nationwide Inpatient Sample were queried for
the occurrence and perforation of acute appendicitis. Risk-adjusted differences
were compared by race/ethnicity over 5-year age increments using logistic
regression with reweighted estimating equations. Noting disparate outcomes
between younger (aged 18-34 years) versus older (aged 35-64 years) adults, age
stratified variations were further considered. Results were compared relative to
differences among national military/civilian-dependent patients with universal
insurance and were assessed for the extent to which disparities could be
explained by variations in insurance and income. RESULTS: A total of 129,257
(weighted: 638,452) patients were included. Despite a lack of differences
overall, significantly worse outcomes among younger (odds ratio point-estimates
ranged from 1.11-1.32) and better outcomes among older (0.78-0.93) minority
patients were found. This observation contrasted a lack of differences among
completely insured military/civilian-dependent patients (n = 12,154). A total of
22.4% (non-Hispanic black versus non-Hispanic white) and 39.0% (Hispanic versus
non-Hispanic white) of younger adult differences were explained by insurance
12.2% and 13.6% by income, 29.8% and 44.0% combined. CONCLUSION: This national
assessment of differences in access to care among adults with acute appendicitis
demonstrated the existence of racial/ethnic disparities in PAAR that varied with
age and were partially, although incompletely, explained by variations in
insurance and income.
PMID- 27486005
TI - Pilot Assessment of the Repeatability of Indocyanine Green Fluorescence Imaging
and Correlation with Traditional Foot Perfusion Assessments.
AB - BACKGROUND: Ankle brachial index (ABI), toe pressures (TP), and transcutaneous
oxygen pressure (TcPO2) are traditionally used in the assessment of critical limb
ischemia (CLI). Indocyanine green (ICG) fluorescence imaging can be used to
evaluate local circulation in the foot and to evaluate the severity of ischemia.
This prospective study analyzed the suitability of a fluorescence imaging system
(photodynamic eye [PDE]) in CLI. MATERIAL AND METHODS: Forty-one patients with
CLI were included. Of the patients, 66% had diabetes and there was an ischemic
tissue lesion in 70% of the limbs. ABI, toe pressures, TcPO2 and ICG-fluorescence
imaging (ICG-FI) were measured in each leg. To study the repeatability of the ICG
FI, each patient underwent the study twice. After the procedure, foot circulation
was measured using a time-intensity curve, where T1/2 (the time needed to achieve
half of the maximum fluorescence intensity) and PDE10 (increase of the intensity
during the first 10 s) were determined. A time-intensity curve was plotted using
the same areas as for the TcPO2 probes (n=123). RESULTS: The mean ABI was 0.43,
TP 21 mmHg, TcPO2 23 mmHg, T1/2 38 s, and PDE10 19 AU. Time-intensity curves were
repeatable. In a Bland-Altman scatter plot, the 95% limits of agreement of PDE10
was 9.9 AU and the corresponding value of T1/2 was 14 s. Correlation between ABI
and TP was significant (R=.73, p<.001), and it was weaker in diabetic patients
(R=.47, p=.048) compared with non-diabetic patients (R=.89, p=.002). Correlations
between ABI and TcPO2 and TP and TcPO2 were weak (R=.37, p=.05 and R=.43, p=.037,
respectively). Correlation between TcPO2 and PDE10 was strong in diabetic
patients (R=.70, p=.003). CONCLUSIONS: According to this pilot study, ICG-FI with
PDE can be used in the assessment of blood supply in the ischemic foot.
PMID- 27486006
TI - Alkyne Metathesis with Silica-Supported and Molecular Catalysts at Parts-per
Million Loadings.
AB - Improvement of the activity, stability, and chemoselectivity of alkyne-metathesis
catalysts is necessary before this promising methodology can become a routine
method to construct C=C triple bonds. Herein, we show that grafting of the known
molecular catalyst [MesC=Mo(OtBuF6 )3 ] (1, Mes=2,4,6-trimethylphenyl, OtBuF6
=hexafluoro-tert-butoxy) onto partially dehydroxylated silica gave a well-defined
silica-supported active alkyne-metathesis catalyst [(=SiO)Mo(=CMes)(OtBuF6 )2 ]
(1/SiO2-700 ). Both 1 and 1/SiO2-700 showed very high activity, selectivity, and
stability in the self-metathesis of a variety of carefully purified alkynes, even
at parts-per-million catalyst loadings. Remarkably, the lower turnover
frequencies observed for 1/SiO2-700 by comparison to 1 do not prevent the
achievement of high turnover numbers. We attribute the lower reactivity of 1/SiO2
700 to the rigidity of the surface Mo species owing to the strong interaction of
the metal site with the silica surface.
PMID- 27486007
TI - Exploratory factor analysis of the reintegration to normal living index in a
stroke population.
AB - BACKGROUND: The reintegration to normal living index (RNLI) is a global
assessment of patient quality of life often utilized in stroke populations.
Previous studies in various general disability samples have consistently reported
a two-factor solution for the RNLI. Despite its common use with stroke patients,
the RNLI has not been psychometrically evaluated in an exclusively stroke sample.
This study is believed to represent the first factor analysis of the RNLI using a
sample comprised exclusively of individuals who have survived cerebral infarct.
OBJECTIVE: The aim of this study is to evaluate the psychometric properties of
the RNLI in assessing quality of life of stroke survivors. METHODS: We
retrospectively examined RNLI scores of 928 adults with strokes of varying
severities as part of a multidisciplinary, interinstitutional collaboration
across an academic medical center, acute care hospital, and rehabilitation
center. We utilized a principal component factor analysis to evaluate the factor
structure of the RNLI. RESULTS: Mean RNLI scores +/-SD for the sample were 75.26
+/- 19.85, ranging between 20 and 100. The Cronbach alpha was .94. A scree test
for factor retention strongly suggested a single factor solution, explaining
64.50% of the total variance. CONCLUSIONS: Previous factor analyses on the RNLI
utilizing general disability samples commonly report a two-factor solution. Our
data support the presence of a single factor solution across the RNLI within a
large sample comprised exclusively of stroke survivors. This suggests that the
RNLI acts as more of a unitary measure of quality of life within a stroke sample
relative to other disabled samples.
PMID- 27486008
TI - Response to Wiewel-Verschueren S et al.: gynaecological and obstetrical bleeding
in women with factor XI deficiency - a systematic review.
PMID- 27486009
TI - Predictors for prolonged interval from premature rupture of membranes to
spontaneous onset of labor at term.
AB - OBJECTIVE: To identify predictors for prolonged interval from premature rupture
of membranes (PROM) to spontaneous onset of labor in women presenting with PROM
and low Bishop score at term. METHODS: A retrospective study of women presenting
with PROM and Bishop score < 7 at term (>=37weeks) in a tertiary hospital (2013
14). Spontaneous onset of labor was defined as presence of regular uterine
contractions and Bishop score >= 7. Women with interval from PROM to spontaneous
onset of labor of <24hours (short interval group) were compared to those with
interval >= 24 hours (prolonged interval group). Women who underwent induction of
labor at < 24 hours from PROM were excluded. RESULTS: Among 625 women who met
inclusion criteria, 155 (24.8%) had a prolonged interval to onset of labor. In
multivariate analysis, prolonged PROM was associated with (OR, 95%CI) cervical
dilatation (0.35, 0.24-0.52, p < 0.001), effacement (0.97, 0.96-0.99, p < 0.001)
and uterine contraction (0.51, 0.32-0.80, p = 0.004). A multivariable prediction
model including maternal age, parity, cervical dilatation and effacement,
gestational age and neonatal birthweight was associated with an AUC of receiver
operator characteristic curve of 0.739 (0.631-0.847, p < 0.001) for predicting
prolonged PROM. CONCLUSION: Uterine contractions and cervical examination
parameters can be used for prediction of prolonged interval to spontaneous onset
of labor in women with term PROM.
PMID- 27486011
TI - Running injuries in novice runners enrolled in different training interventions:
a pilot randomized controlled trial.
AB - : The purpose of this trial was to evaluate injury risk in novice runners
participating in different strength training interventions. This was a pilot
randomized controlled trial. Novice runners (n = 129, 18-60 years old, <2 years
recent running experience) were block randomized to one of three groups: a
"resistance" strength training group, a "functional" strength training group, or
a stretching "control" group. The primary outcome was running related injury. The
number of participants with complaints and the injury rate (IR = no.
injuries/1000 running hours) were quantified for each intervention group. For the
first 8 weeks, participants were instructed to complete their training
intervention three to five times a week. The remaining 4 months was a maintenance
period. TRIAL REGISTRATION: NCT01900262. A total of 52 of the 129 (40%) novice
runners experienced at least one running related injury: 21 in the functional
strength training program, 16 in the resistance strength training program and 15
in the control stretching program. Injury rates did not differ between study
groups [IR = 32.9 (95% CI 20.8, 49.3) in the functional group, IR = 31.6 (95% CI
18.4, 50.5) in the resistance group, and IR = 26.7 (95% CI 15.2, 43.2)] in the
control group. Although this was a pilot assessment, home-based strength training
did not appear to alter injury rates compared to stretching. Future studies
should consider methods to minimize participant drop out to allow for the
assessment of injury risk. Injury risk in novice runners based on this pilot
study will inform the development of future larger studies investigating the
impact of injury prevention interventions.
PMID- 27486012
TI - Ocular morphology and function in juvenile neuronal ceroid lipofuscinosis (CLN3)
in the first decade of life.
AB - PURPOSE: CLN3 is a rare lysosomal storage disorder. The majority of the patients
suffer from neurological degeneration in the first decade of life leading to
death in the second or third decade. One of the first symptoms is a rapid visual
decline from retinal degeneration. The aim of this study was to correlate the
retinal changes in CLN3 as seen with spectral domain optical coherence tomography
(SD-OCT) with functional data in patients in the first years after the subjective
onset of ocular symptoms. METHODS: Three unrelated children aged from 5.6 to 8.8
years, and with molecularly confirmed CLN3, underwent a comprehensive
ophthalmological examination including visual acuity, fundus photography, fundus
autofluorescence (FAF), electrophysiology (multifocal ERG), Goldmann visual
fields, and SD-OCT. RESULTS: A predominant loss of the first and second neuron
retinal layers progressing from the macula to the periphery was identifed. The
retinal nerve fibre layer (RNFL) displayed gliosis and an irregular lining of the
inner limiting membrane. Compared to the preferential reduction of photoreceptor
layer thickness in other maculopathies with pan-retinal involvement, the
thickness of the first and second neuron layers was reduced simultaneously in
CLN3. Functional testing by multifocal ERG reflected the degenerative progress.
Semiquantitative evaluation revealed a generally reduced FAF. CONCLUSION: This is
the first detailed morphological evaluation of CLN3 patients in the first years
after the subjective onset of ocular symptoms. CLN3 is characterized by an early
degeneration predominant of the first and second neuron compared to other macular
and generalized retinal dystrophies. Imaging is instrumental for early diagnosis
and gene-directed molecular analysis of this fatal disorder.
PMID- 27486010
TI - NAFLD and liver transplantation: Current burden and expected challenges.
AB - Because of global epidemics of obesity and type 2 diabetes, the prevalence of non
alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United
States, becoming one of the most frequent causes of chronic liver disease and
predictably, one of the leading causes of liver transplantation both for end
stage liver disease and hepatocellular carcinoma. For most transplant teams
around the world this will raise many challenges in terms of pre- and post
transplant management. Here we review the multifaceted impact of NAFLD on liver
transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic
cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2)
prevalence of NAFLD as an indication for liver transplantation both in Europe and
the United States; (3) the impact of NAFLD on the donor pool; (4) the access of
NAFLD patients to liver transplantation and their management on the waiting list
in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and
consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD;
(6) the alternative management and therapeutic options to improve the long-term
outcomes with particular emphasis on the correction and control of metabolic
comorbidities.
PMID- 27486013
TI - A current snapshot of common genomic variants contribution in psychiatric
disorders.
AB - In the past decade, numerous advances were achieved in psychiatric genetics.
Particularly, the genome wide association studies (GWAS) have contributed to
uncovering new genes and pathways associated to psychiatric disorders (PDs). At
the same time, with increasing sample sizes in the GWAS, the polygenic risk score
(PRS) promoted an additional tool for identification and evaluation the genetic
risk quantitatively in PDs. This concept review presents the state of the art
GWAS analysis and PRS focusing on the genetic underpinnings of PDs. (c) 2016
Wiley Periodicals, Inc.
PMID- 27486014
TI - 10 weeks of heavy strength training improves performance-related measurements in
elite cyclists.
AB - Elite cyclists have often a limited period of time available during their short
preparation phase to focus on development of maximal strength; therefore, the
purpose of the present study was to investigate the effect of 10-week heavy
strength training on lean lower-body mass, leg strength, determinants of cycling
performance and cycling performance in elite cyclists. Twelve cyclists performed
heavy strength training and normal endurance training (E&S) while 8 other
cyclists performed normal endurance training only (E). Following the intervention
period E&S had a larger increase in maximal isometric half squat, mean power
output during a 30-s Wingate sprint (P < 0.05) and a tendency towards larger
improvement in power output at 4 mmol ? L-1 [la-] than E (P = 0.068). There were
no significant difference between E&S and E in changes in 40-min all-out trial (4
+/- 6% vs. -1 +/- 6%, respectively, P = 0.13). These beneficial effects may
encourage elite cyclists to perform heavy strength training and the short period
of only 10 weeks should make it executable even in the compressed training and
competition schedule of elite cyclists.
PMID- 27486016
TI - Implementation of an Educational Cartoon ("the Patchbook") and Other Compliance
Enhancing Measures by Orthoptists in Occlusion Treatment of Amblyopia.
AB - PURPOSE: This implementation study evaluated orthoptists' use of an educational
cartoon ("the Patchbook") and other measures to improve compliance with occlusion
therapy for amblyopia. METHODS: Participating orthoptists provided standard
orthoptic care for one year, adding the Patchbook in the second year. They
attended courses on compliance and intercultural communication by communication
skills training. Many other compliance-enhancing measures were initiated.
Orthoptists' awareness, attitude, and activities regarding noncompliance were
assessed through interviews, questionnaires, and observations. Their use of the
Patchbook was measured. The study was performed in low socio-economic status
(SES) areas and in other areas in the Netherlands. It was attempted to integrate
education on compliance into basic and continuing orthoptic training. RESULTS:
The Patchbook was used by all 9 orthoptists who participated in low-SES areas and
17 of 23 orthoptists in other areas. Courses changed awareness and attitude about
compliance, but this was not sustained. Although orthoptists estimated compliance
during patching at 70%, three-quarters never suspected noncompliance during a
full day of observation in any of their patients. Explanations to parents who
spoke Dutch poorly were short. In the second year, explanations to children were
longer. Implementation of all 7 additional compliance-enhancing measures failed.
Education on compliance was not integrated into orthoptists' training.
CONCLUSION: Almost all orthoptists used the Patchbook and, as another study
demonstrated, it proved to be very effective, especially in low-SES areas.
Duration of explanation was inversely proportional to parents' fluency in Dutch.
Noncompliance was rarely suspected by orthoptists. Although 7 additional
compliance-enhancing measures had been conceived and planned with the best
intentions, they were not realized. These required extra, unpaid time from the
orthoptists, which is especially scarce in hospitals in low-SES areas where the
educational cartoon is most needed.
PMID- 27486015
TI - Dynamic mRNA and miRNA expression analysis in response to intermuscular bone
development of blunt snout bream (Megalobrama amblycephala).
AB - Intermuscular bone (IB), which occurs only in the myosepta of lower teleosts, is
attracting more attention because they are difficult to remove and make the fish
unpleasant to eat. By gaining a better understanding of the genetic regulation of
IB development, an integrated analysis of miRNAs and mRNAs expression profiling
was performed on Megalobrama amblycephala. Four key development stages were
selected for transcriptome and small RNA sequencing. A number of significantly
differentially expressed miRNAs/genes associated with bone formation and
differentiation were identified and the functional characteristics of these
miRNAs/genes were revealed by GO function and KEGG pathway analysis. These were
involved in TGF-beta, ERK and osteoclast differentiation pathways known in the
literature to affect bone formation and differentiation. MiRNA-mRNA interaction
pairs were detected from comparison of expression between different stages. The
function annotation results also showed that many miRNA-mRNA interaction pairs
were likely to be involved in regulating bone development and differentiation. A
negative regulation effect of two miRNAs was verified through dual luciferase
reporter assay. As a unique public resource for gene expression and regulation
during the IB development, this study is expected to provide forwards ideas and
resources for further biological researches to understand the IBs' development.
PMID- 27486017
TI - Effects of intermittent pneumatic compression of the thigh on blood flow velocity
in the femoral and popliteal veins: developing a new physical prophylaxis for
deep vein thrombosis in patients with plaster-cast immobilization of the leg.
AB - Patients with plaster-cast immobilization of the lower limb have an estimated
venous thromboembolism rate of 2.5 % without prophylaxis, which includes many
fatal cases. However, there is no practical physical prophylaxis for deep-vein
thrombosis (DVT) in these patients. The aim of this study was to examine the
effects of intermittent pneumatic compression on the thigh alone (IPC to the
thigh) on peak blood velocity (PBV) in the legs and to consider the possibility
that IPC of the thigh could be used as physical prophylaxis for DVT in patients
with plaster-cast immobilization of the lower leg. Nine healthy male volunteers
and eighteen elderly males were recruited. We immobilized each subject's right
lower leg and ankle with a plaster splint, and applied the ActiveCare+S.F.T.((r))
(Medical Compression Systems, Inc.) device to each subject's right thigh. The PBV
in the superficial femoral vein (PBVFV) and the popliteal vein (PBVPV) were
measured using duplex Doppler ultrasonography. IPC to the thigh resulted in a 2.3
fold increase in PBVFV and a 3.0-fold increase in PBVPV compared with resting at
supine in the elderly group. Although IPC to the thigh also increased PBVFV and
PBVPV significantly in the sitting position, the change ratios of PBV in the
supine and sitting positions were equal (2.6-fold increase in PBVFV and 2.9-fold
increase in PBVPV). IPC to the thigh in supine and sitting positions
significantly increased PBVFV and PBVPV, and could be a useful prophylaxis for
DVT in patients with plaster-cast immobilization of the lower leg.
PMID- 27486018
TI - Effect of infertility on quality of life of women: a validation study of the
Turkish FertiQoL.
AB - The fertility quality of life (FertiQoL) measure specifically evaluates the
impact of fertility problems in various life areas. The aim of this study was to
examine the relationship between FertiQoL and the hospital anxiety and depression
scale (HADS) in the Turkish population. All female patients who underwent various
fertility treatments in our infertility clinic from May 2011 to May 2014 were
approached to participate in the study and 389 completed the questionnaires. Our
results showed that the four core scales of the FertiQoL measure had a Cronbach's
alpha value that was between 0.70 and 0.89. Two scales (anxiety and depression)
of HADS both had a Cronbach's alpha value of 0.80. These values present a
reliable usage of FertiQoL and HADS measures (alpha > 0.60). Significant negative
correlations were found between the FertiQoL scales and HADS scales, ranging from
-0.27 (between relational scale of FertiQoL and anxiety scale of HADS) to -0.65
(between mind-body scale of FertiQoL and depression scale of HADS). The results
of this study provide supportive data to confirm that the Turkish version of
FertiQol can accurately evaluate QoL in women who seek fertility treatment in
Turkey.
PMID- 27486019
TI - Rare Variation in TET2 Is Associated with Clinically Relevant Prostate Carcinoma
in African Americans.
AB - BACKGROUND: Common variants have been associated with prostate cancer risk.
Unfortunately, few are reproducibly linked to aggressive disease, the phenotype
of greatest clinical relevance. One possible explanation is that rare genetic
variants underlie a significant proportion of the risk for aggressive disease.
METHOD: To identify such variants, we performed a two-stage approach using whole
exome sequencing followed by targeted sequencing of 800 genes in 652 aggressive
prostate cancer patients and 752 disease-free controls in both African and
European Americans. In each population, we tested rare variants for association
using two gene-based aggregation tests. We established a study-wide significance
threshold of 3.125 * 10-5 to correct for multiple testing. RESULTS: TET2 in
African Americans was associated with aggressive disease, with 24.4% of cases
harboring a rare deleterious variant compared with 9.6% of controls (FET P = 1.84
* 10-5, OR = 3.0; SKAT-O P = 2.74 * 10-5). We report 8 additional genes with
suggestive evidence of association, including the DNA repair genes PARP2 and MSH6
Finally, we observed an excess of rare truncation variants in 5 genes, including
the DNA repair genes MSH6, BRCA1, and BRCA2 This adds to the growing body of
evidence that DNA repair pathway defects may influence susceptibility to
aggressive prostate cancer. CONCLUSIONS: Our findings suggest that rare variants
influence risk of clinically relevant prostate cancer and, if validated, could
serve to identify men for screening, prophylaxis, and treatment. IMPACT: This
study provides evidence that rare variants in TET2 may help identify African
American men at increased risk for clinically relevant prostate cancer. Cancer
Epidemiol Biomarkers Prev; 25(11); 1456-63. (c)2016 AACR.
PMID- 27486020
TI - Missing the Target for Routine Human Papillomavirus Vaccination: Consistent and
Strong Physician Recommendations Are Lacking for 11- to 12-Year-Old Males.
AB - BACKGROUND: Rates of routine human papillomavirus (HPV) vaccination of adolescent
males in the United States are low. Leading health organizations advocate
consistent and strong physician recommendations to improve HPV vaccine
dissemination. This study describes the prevalence and correlates of consistent
and strong physician recommendations for HPV vaccination of adolescent males.
METHODS: We surveyed pediatric and family medicine physicians in Florida about
their HPV vaccine recommendations for male vaccine-eligible age groups (11-12, 13
17, 18-21 years). Descriptive statistics compared consistency and strength of HPV
recommendations across age groups. Multivariable logistic regression examined
factors associated with consistent and strong recommendations for 11- to 12-year
olds. RESULTS: We received 367 completed surveys (51% response rate). Physicians
most often consistently and strongly recommended HPV vaccine to males ages 13 to
17 (39%) compared with ages 11 to 12 (31%) and 18 to 21 (31%). Consistent and
strong recommendation for 11- to 12-year-old males was more likely to be
delivered by Vaccine for Children providers and less likely among physicians who
reported more personal barriers to vaccination, particularly concerns about
vaccine safety, concerns about adding vaccines to the vaccine schedule, and
difficulty in remembering to discuss HPV vaccination. CONCLUSIONS: Physicians'
current consistency and strength of HPV vaccine recommendations do not align with
national recommendations. Interventions to improve HPV vaccine recommendations
must also consider the influence of physicians' personal barriers to HPV vaccine
delivery. IMPACT: As one of the first studies to examine both consistency and
strength of physicians' HPV vaccine recommendations for males, our findings can
inform future interventions focused on facilitating physicians' recommendations.
Cancer Epidemiol Biomarkers Prev; 25(10); 1435-46. (c)2016 AACR.
PMID- 27486021
TI - Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal
cortex under the pathological conditions of Alzheimer's disease.
AB - Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop
in the elderly, is characterized by the deposition of beta-amyloid protein
(Abeta) and extensive neuronal cell death in the brain. Neuregulin-1 (Nrg1)
mediated intercellular and intracellular communication via binding to ErbB
receptors regulates a diverse set of biological processes involved in the
development of the nervous system. In the present study, a linear correlation was
identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a
human cortical tissue microarray. In addition, increased expression levels of
Nrg1, but reduced pErbB receptor levels, were detected in the frontal lobe of a
patient with AD. Western blotting and immunofluorescence staining were
subsequently performed to uncover the potential preventive role of Nrg1 in
cortical neurons affected by the neurodegenerative processes of AD. It was
observed that the expression of Nrg1 increased as the culture time of the
cortical neurons progressed. In addition, H2O2 and Abeta1-42, two inducers of
oxidative stress and neuronal damage, led to a dose-dependent decrease in Nrg1
expression. Recombinant Nrg1beta, however, was revealed to exert a pivotal role
in preventing oxidative stress and neuronal damage from occurring in the mouse
cortical neurons. Taken together, these results suggest that changes in Nrg1
signaling may influence the pathological development of AD, and exogenous Nrg1
may serve as a potential candidate for the prevention and treatment of AD.
PMID- 27486022
TI - Comparative evaluation of outcomes of phacoemulsification in vitrectomized eyes:
silicone oil versus air/gas group.
AB - The purpose of this study is to comparatively evaluate the morphology of
cataract, intraoperative and postoperative complications (IPC), and surgical
outcomes of phacoemulsification in post 23G vitrectomized eyes in silicone oil
versus air/gas group. This prospective interventional clinical study took place
in the Dr. RP Centre for Ophthalmic Sciences, AIIMS, New Delhi, India. Eighty
nine eyes of 89 consecutive vitrectomized patients with cataract were included.
All underwent phacoemulsification and evaluated for cataract morphology, surgical
difficulties, IPC, visual acuity, and specular count. Mean age of patients was
50.24 +/- 15.19 years. There were 65 males and 24 females and 48 eyes in silicone
oil group and 41 in air/gas group. Combination type was the commonest morphology
seen in both silicone oil (52.08 %) and air/gas group (70.33 %) followed by
posterior subcapsular cataract (PSC) in 31.25 % silicone group and 12.2 % air/gas
group. Posterior capsular plaque (PCP) was seen in 41.67 % of silicone oil versus
7.32 % air/gas group; p < 0.005. Pupillary abnormalities were significantly more
in oil (31.25 %) than in air/gas group (9.76 %); p = 0.014. Mean duration between
vitrectomy and phacoemulsification in oil group versus air/gas group was 8.39 +/-
4.7 months and 10.9 +/- 5.22 months, respectively; p < 0.005. Mean postoperative
logMAR visual acuity was better in air/gas (0.43 +/- 0.25) than in oil (0.66 +/-
0.29) group, p < 0.005. There was no significant difference in mean endothelial
cell loss postoperatively in either groups (p = 0.25). Morphology of cataract
differs in the two groups with PSC being more common in oil group. The mean time
of cataract onset was significantly less in patients with oil group, and poor
visual outcome in oil group may be attributable to the increased PCP noted.
PMID- 27486023
TI - Enhanced depth imaging is less suited than indocyanine green angiography for
close monitoring of primary stromal choroiditis: a pilot report.
AB - The purpose of this study is to investigate the performance, utility, and
precision of enhanced depth imaging optical coherence tomography (EDI-OCT) versus
indocyanine green angiography (ICGA) in tracking any fluctuation in the activity
of stromal choroiditis in response to therapeutic interventions during long-term
follow-up. Patients with a diagnosis of Vogt-Koyanagi-Harada (VKH) disease or
birdshot retinochoroiditis (BRC), with untreated initial disease, and having had
long-term follow-up, including both ICGA and EDI-OCT, were recruited at the
Centre for Ophthalmic Specialised care, Lausanne, Switzerland. Angiography signs
were quantified according to established dual fluorescein angiography (FA) and
ICGA scoring systems for uveitis. Changes in ICGA score and EDI choroidal
thickness, in response to therapeutic intervention, were assessed. In the four
eyes analysed (2 BRC and 2 VKH), mean EDI-OCT choroidal thickness decreased from
672 +/- 101 um at presentation to 358.5 +/- 44.5 um in a mean of 26.5 months,
i.e. the time taken to stabilize the disease. Mean ICGA scores decreased from 28
+/- 4.2 at presentation to 5 +/- 7 at stabilization. Only ICGA was sufficiently
sensitive and reactive having the ability to detect disease recurrences and
efficacy or the absence of effect of successive treatment changes, detected in
seven instances during follow-up, not recorded by EDI-OCT. This pilot study
showed that ICGA was a more sensitive methodology, which promptly identifies
evolving subclinical and occult choroidal disease, and flag occult recurrence
and/or therapeutic responses that were otherwise missed by EDI-OCT. Although
choroidal thickness was proportional to treatment course, demonstrating a linear
decrease, these changes were too sluggish to be relied upon for close follow-up
and timely adjustment of therapy.
PMID- 27486024
TI - Opening of the inward rectifier potassium channel alleviates maladaptive tissue
repair following myocardial infarction.
AB - Activation of the inward rectifier potassium current (IK1) channel has been
reported to be associated with suppression of ventricular arrhythmias. In this
study, we tested the hypothesis that opening of the IK1 channel with zacopride
(ZAC) was involved in the modulation of tissue repair after myocardial
infarction. Sprague-Dawley rats were subject to coronary artery ligation and ZAC
was administered intraperitoneally (15 ug/kg/day) for 28 days. Compared with the
ischemia group, treatment with ZAC significantly reduced the ratio of heart/body
weight and the cross-sectional area of cardiomyocytes, suggesting less cardiac
hypertrophy. ZAC reduced the accumulation of collagen types I and III,
accompanied with decrease of collagen area, which were associated with a
reduction of collagen deposition in the fibrotic myocardium. Echocardiography
showed improved cardiac function, evidenced by the reduced left ventricular end
diastolic dimension and left ventricular end-systolic dimension, and the
increased ejection fraction and fractional shortening in ZAC-treated animals (all
P < 0.05 vs. ischemia group). In coincidence with these changes, ZAC up-regulated
the protein level of the IK1 channel and down-regulated the phosphorylation of
mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 (p70S6)
kinase. Administration of chloroquine alone, an IK1 channel antagonist, had no
effect on all the parameters measured, but significantly blocked the beneficial
effects of ZAC on cardiac repair. In conclusion, opening of the IK1 channel with
ZAC inhibits maladaptive tissue repair and improves cardiac function, potentially
mediated by the inhibition of ischemia-activated mTOR-p70S6 signaling pathway via
the IK1 channel. So the development of pharmacological agents specifically
targeting the activation of the IK1 channel may protect the heart against
myocardial ischemia-induced cardiac dysfunction.
PMID- 27486025
TI - Haplotype distribution and association of candidate genes with salt tolerance in
Indian wild rice germplasm.
AB - KEY MESSAGE: The association of natural genetic variations of salt-responsive
candidate genes belonging to different gene families with salt-tolerance
phenotype and their haplotype variation in different geographic regions. Soil
salinity covers a large part of the arable land of the world and is a major
factor for yield losses in salt-sensitive crops, such as rice. Different gene
families that respond to salinity have been identified in rice, but limited
success has been achieved in developing salt-tolerant cultivars. Therefore, 21
salt stress-responsive candidate genes belonging to different gene families were
re-sequenced to analyse their genetic variation and association with salt
tolerance. The average single nucleotide polymorphism (SNP) density was 16 SNPs
per kbp amongst these genes. The identified nucleotide and haplotype diversity
showed comparatively higher genetic variation in the transporter family genes.
Linkage disequilibrium (LD) analysis showed significant associations of SNPs in
BADH2, HsfC1B, MIPS1, MIPS2, MYB2, NHX1, NHX2, NHX3, P5CS1, P5CS2, PIP1, SIK1,
SOS1, and SOS2 genes with the salt-tolerant phenotype. A combined analysis of
SNPs in the 21 candidate genes and eight other HKT transporter genes produced two
separate clusters of tolerant genotypes, carrying unique SNPs in the ion
transporter and osmoticum-related genes. Haplotype network analysis showed all
the major and few minor alleles distributed over distant geographic regions.
Minor haplotypes may be recently evolved alleles which migrated to distant
geographic regions and may represent recent expansion of Indian wild rice. The
analysis of genetic variation in different gene families identified the
relationship between adaptive variations and functional significance of the
genes. Introgression of the identified alleles from wild relatives may enhance
the salt tolerance and consequently rice production in the salinity-affected
areas.
PMID- 27486027
TI - Fertility Awareness Counseling for Adolescent Girls; Guiding Conception: The
Right Time, Right Weight, and Right Way.
AB - STUDY OBJECTIVE: To provide a detailed summary of fertility awareness counseling
pearls for healthy teens and those with fertility-relevant comorbidities, and to
assist providers in offering such counseling to adolescents and young adult
women. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES:
Comprehensive literature review of English-language studies relating to fertility
in pediatric and adolescent female patients (ages 13-21 years), and evidence
based dialogue guide. RESULTS: The literature indicates that although adolescents
are interested in discussing sexuality and reproduction, this is commonly
overlooked during the standard office medical visit. As a result, adolescents
often turn to less reliable sources and hold a variety of reproductive
misconceptions and a sense of lack of control over future fertility. We found no
studies that examined the routine provision of fertility awareness counseling
with healthy adolescents. There are a multitude of specific gynecologic and
medical conditions that have ramifications for fertility. We detail these
comprehensively, and provide a dialogue guide to assist with fertility awareness
counseling for the female adolescent, containing specific information and
indications for referral. CONCLUSION: Providers caring for adolescent girls have
the opportunity to enhance fertility awareness as part of a larger reproductive
health conversation that adolescents desire, and from which they might benefit.
Identifying potential future fertility issues, understanding age-related
fertility decline, and aiding in health optimization before future conception
might empower the adolescent to make informed reproductive decisions. We provide
an algorithm to use with adolescents to discuss the "right time, right weight,
right way" to pursue childbearing.
PMID- 27486028
TI - Service users' expectations of treatment and support at the Community Mental
Health Centre in their recovery.
AB - BACKGROUND: Focus on service users' needs, coping and empowerment, user
involvement, and comprehensiveness are supposed to be key elements of the
Community Mental Health Centres in Norway. Taking a user-oriented approach means
acknowledging the individual's own expectations, aims and hopes. However, studies
that have investigated service users' expectations of treatment and support at
Community Mental Health Centres are hard to find. OBJECTIVE: The aim of the study
was therefore to explore service users' expectations at the start of treatment at
a Community Mental Health Centre. METHOD: Within a collaborative framework,
taking a hermeneutic-phenomenological approach, ten service users participated in
in-depth interviews about their expectations, hopes and aims for treatment and
recovery. The participants sought help due to various mental health issues that
had interfered with their lives and created disability and suffering. A data
driven stepwise approach in line with thematic analysis was used. The study was
approved by the Norwegian Social Science Data Services. RESULTS: The following
four main themes representing participants' expectations at the start of
treatment were elicited: hope for recovery, developing understanding, finding
tools for coping and receiving counselling and practical assistance.
Participants' expectations about treatment were tightly interwoven with their
personal aims and hopes for their future life, and expectations were often
related to practical and financial problems, the solution of which being deemed
necessary to gain a safe basis for recovery in the long run. LIMITATIONS: The
transferability of the results may be limited by the small number of
participants. CONCLUSIONS: The study emphasises how important it is that service
users' personal aims and expectations guide the collaborative treatment process.
In addition to providing treatment aimed at improving symptoms, Community Mental
Health Centres should take a more comprehensive approach than today by providing
more support with family issues, social life, education, work and financial
issues.
PMID- 27486029
TI - A case of endocarditis mimicking Crimean-Congo haemorrhagic fever.
AB - Infective endocarditis (IE) is life-threatening condition with a highly variable
clinical presentation. We report a case of acute IE with delayed diagnosis which
resulted due to an initial misdiagnosis of Crimean Congo Hemorrhagic Fever (CCHF)
in an endemic area. A case was due to Staphylococcus aureus and requiring valve
replacement. They serve to emphasize the importance of careful history taking,
physical examination and a broad range of different diagnostic techniques in the
context of suspected viral hemorrhagic fever.
PMID- 27486031
TI - Diagnostic accuracy of individual antenatal tools for prediction of small-for
gestational age at birth.
AB - OBJECTIVE: To determine the accuracy of fetal and newborn growth charts for the
prediction of small-for-gestational age (SGA) at birth (birth weight < 10th
centile). METHODS: This was a prospective cohort study performed within a UK
specialist fetal growth clinic. A total of 105 consecutive pregnant women
referred for a suspected SGA fetus were included. All pregnancies were managed
according to a standard protocol using estimated fetal weight (EFW) plotted on
customized Gestation Related Optimal Weight (GROW) charts. The last antenatal
estimates of EFW (according to charts of GROW, Hadlock et al. and Mikolajczyk et
al.), abdominal circumference (AC) (according to charts of Hadlock et al.,
INTERGROWTH-21st Project and Chitty et al.) or change in AC over time (calculated
according to Pregnancy Outcome Prediction (POP) study) were compared against four
birth-weight charts (GROW, INTERGROWTH-21st , Mikolajczyk et al. and World Health
Organization (WHO)). The ability of each antenatal test to predict adverse
perinatal outcome (APO) was assessed. RESULTS: Birth weight < 10th centile was
assigned in 62 (59%) neonates using the GROW chart, 57 (54%) using the
Mikolajczyk et al. chart, 55 (52%) using the INTERGROWTH-21st chart and 51 (49%)
using the WHO chart. AC-Hadlock had the best negative likelihood ratio (range,
0.3-0.4) and sensitivity (range, 74%-82%) for predicting SGA as defined by all
four postnatal birth-weight charts. AC-INTERGROWTH-21st had the best positive
likelihood ratio (range, 5.9-10.9) and specificity (94%-96%). For prediction of
APO, AC-Hadlock and EFW-GROW had the best sensitivities (57% and 52%,
respectively), whereas AC-POP had the best positive likelihood ratio (2.2) and
specificity (88%). Antenatal prediction of APO increased to a sensitivity of 61%
when AC-POP and EFW-GROW were combined; however, specificity was only 56%.
CONCLUSIONS: We have identified wide variation in the diagnostic accuracy of
various antenatal tools for the prediction of both SGA and APO, dependent on the
choice of chart. Suboptimal diagnostic accuracy of commonly used antenatal tests
may lead to increasing medicalization without prevention of APO. Researchers
should focus their attention on a combination of fetal biometry and biomarkers
for better prediction of SGA and prevention of APO. Copyright (c) 2016 ISUOG.
Published by John Wiley & Sons Ltd.
PMID- 27486032
TI - Desulfovibrio vulgaris CbiKP cobaltochelatase: evolution of a haem binding
protein orchestrated by the incorporation of two histidine residues.
AB - The sulfate-reducing bacteria of the Desulfovibrio genus make three distinct
modified tetrapyrroles, haem, sirohaem and adenosylcobamide, where
sirohydrochlorin acts as the last common biosynthetic intermediate along the
branched tetrapyrrole pathway. Intriguingly, D. vulgaris encodes two
sirohydrochlorin chelatases, CbiKP and CbiKC , that insert cobalt/iron into the
tetrapyrrole macrocycle but are thought to be distinctly located in the periplasm
and cytoplasm respectively. Fusing GFP onto the C-terminus of CbiKP confirmed
that the protein is transported to the periplasm. The structure-function
relationship of CbiKP was studied by constructing eleven site-directed mutants
and determining their chelatase activities, oligomeric status and haem binding
abilities. Residues His154 and His216 were identified as essential for metal
chelation of sirohydrochlorin. The tetrameric form of the protein is stabilized
by Arg54 and Glu76, which form hydrogen bonds between two subunits. His96 is
responsible for the binding of two haem groups within the main central cavity of
the tetramer. Unexpectedly, CbiKP is shown to bind two additional haem groups
through interaction with His103. Thus, although still retaining cobaltochelatase
activity, the presence of His96 and His103 in CbiKP , which are absent from all
other known bacterial cobaltochelatases, has evolved CbiKP a new function as a
haem binding protein permitting it to act as a potential haem chaperone or
transporter.
PMID- 27486033
TI - Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C
Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial.
AB - BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for
patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections
whose prior course of antiviral therapy has failed, and the feasibility of
shortening treatment duration. We performed a phase 2 study to determine the
efficacy and safety of the combination of the nucleotide polymerase inhibitor
sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS
9857 in these patients. METHODS: We performed a multicenter, open-label trial at
32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to
April 27, 2015. Our study included 128 treatment-naive and treatment-experienced
patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3;
17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated
cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose
combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary
end point was sustained virologic response 12 weeks after treatment (SVR12).
RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment
naive patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%).
After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naive
patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment,
SVR12s were achieved by all treatment-experienced patients without cirrhosis (36
of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis
(28 of 29; 95% CI, 82%-100%). The most common adverse events were headache,
diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to
adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir
velpatasvir plus GS-9857 (8 weeks in treatment-naive patients or 12 weeks in
treatment-experienced patients) to be safe and effective for patients with HCV
genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis.
ClinicalTrials.gov ID: NCT02378961.
PMID- 27486034
TI - Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Genotype 1
Hepatitis C Virus Infection in an Open-Label, Phase 2 Trial.
AB - BACKGROUND & AIMS: The best regimen to re-treat patients who do not respond to
direct-acting antivirals (DAAs) and the feasibility of further shortening
regimens is unclear. We assessed the efficacy and safety of the combination of
the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir,
and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus
genotype 1 infection. METHODS: We performed an open-label trial at 32 sites in
the United States and at 2 sites in New Zealand of 197 patients with genotype 1
hepatitis C virus infection, with or without compensated cirrhosis, who were
treatment-naive or were treated previously with a DAA. Between March 2, 2015, and
September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a
fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus
ribavirin for 1 treatment group consisting of treatment-naive patients with
cirrhosis. The primary end point was sustained virologic response 12 weeks after
treatment (SVR12). RESULTS: Among treatment-naive patients without cirrhosis, 71%
(24 of 34; 95% confidence interval [CI], 53-85) achieved SVR12 after 6 weeks of
treatment and 100% (36 of 36; 95% CI, 90%-100%) achieved SVR12 after 8 weeks of
treatment. Among treatment-naive patients with cirrhosis, 94% (31 of 33; 95% CI,
80-99) achieved SVR12 after 8 weeks of treatment and 81% (25 of 31; 95% CI, 63
93) achieved SVR12 after 8 weeks of treatment with ribavirin. Among DAA
experienced patients treated for 12 weeks, 100% without cirrhosis (31 of 31; 95%
CI, 89-100) and 100% with cirrhosis (32 of 32; 95% CI, 89-100) achieved SVR12.
The most common adverse events were headache, diarrhea, fatigue, and nausea. One
patient (<1%) discontinued treatment because of adverse events. CONCLUSIONS: In a
phase 2 open-label trial, we found 8 weeks of treatment with sofosbuvir
velpatasvir plus GS-9857 to be safe and effective in treatment-naive patients; 12
weeks was safe and effective in patients previously treated with DAAs. The
combination was safe and effective in patients with or without compensated
cirrhosis. Clinicaltrials.gov no: NCT02378935.
PMID- 27486036
TI - Hybrids of the Benzofuran Core from Natural Products and the 2,4-Dihydroxy-5
isopropylbenzene Fragment as Potent Hsp90 Inhibitors: Design, Synthesis and
Bioevaluation.
AB - Several chemical fragments have been confirmed as highly efficient cores for the
design of Hsp90 inhibitors. Molecular hybridization of potent fragments has been
widely used as a rational drug discovery strategy. In this study, a novel class
of hybrids of benzofuran, a privileged core from natural products, and 2,4
dihydroxy-5-isopropyl phenyl, an efficient fragment in Hsp90 inhibitors, were
designed and synthesized. Subsequent evaluation confirmed they inhibited cell
proliferation and regulated the level of client proteins through Hsp90
inhibition. Some of the hybrids can serve as leads to obtain novel chemotypes of
Hsp90 inhibitors. The methods reported here may expand the range of known
structural types accommodated by the ATP binding site of Hsp90.
PMID- 27486035
TI - [Characteristics of potentially inappropriate prescribing of drugs in elderly
polypathological patients].
AB - OBJECTIVE: To analyse potentially inappropriate prescribing (PIP) in elderly
polypathological patients (PP). METHOD: Multicentre observational, prospective
study of 672 patients aged 75 years and older hospitalised in Internal Medicine
between April 2011 and March 2012. The Beers, STOPP-START and ACOVE criteria were
used to detect potentially inappropriate prescribing and the results of PP and
non-PP patients were compared. RESULTS: Of the 672 patients included, 419 (62%)
were polypathological, of which 89.3% met PIP criteria versus 79.4% of non
polypathological patients (p <0.01). 40.3% of polypathological patients met at
least one Beers criteria, 62.8% at least one STOPP criteria, 62.3% at least one
START criteria and 65.6% at least one ACOVE criteria. The rate of potentially
inappropriate prescribing was higher in polypathological patients regardless of
the tool used. CONCLUSIONS: Given the high rate of potentially inappropriate
prescribing in polypathological patients, strategies to improve prescribing
adequacy must be developed.
PMID- 27486037
TI - A Combinational Strategy of Model Disturbance and Outlier Comparison to Define
Applicability Domain in Quantitative Structural Activity Relationship.
AB - In order to define an applicability domain for quantitative structure-activity
relationship modeling, a combinational strategy of model disturbance and outlier
comparison is developed. An indicator named model disturbance index was defined
to estimate the prediction error. Moreover, the information of the outliers in
the training set was used to filter the unreliable samples in the test set based
on "structural similarity". Chromatography retention indices data were used to
investigate this approach. The relationship between model disturbance index and
prediction error can be found. Also, the comparison between the outlier set and
the test set could provide additional information about which unknown samples
should be paid more attentions. A novel technique based on model population
analysis was used to evaluate the validity of applicability domain. Finally,
three commonly used methods, i.e. Leverage, descriptor range-based and model
perturbation method, were compared with the proposed approach.
PMID- 27486038
TI - Network Analysis of Publications on Topological Indices from the Web of Science.
AB - In this paper we analyze a collection of bibliographic networks, constructed from
the data from the Web of Science on works (papers, books, etc.) on the topic of
topological indices and on relating scientific fields. We present the general
outlook and more specific findings about authors, works and journals, subtopics
and keywords and also important relations between them based on scientometric
approaches like the strongest and main citation paths, the main themes on
citation path based on keywords, results of co-authorship analysis in form of the
most prominent islands of citing authors, groups of collaborating authors, two
mode cores of authors and works. We investigate the nature of citing of authors,
important journals and citing of works between them, journals preferred by
authors and expose hierarchy of similar collaborating authors, based on keywords
they use. We perform temporal analysis on one important journal as well. We give
a comprehensive scientometric insight into the field of topological indices.
PMID- 27486039
TI - Design Some New Type-I c-met Inhibitors Based on Molecular Docking and Topomer
CoMFA Research.
AB - In this paper, a specific design strategy targeting c-met kinase was reported
based on docking modeling and topomer comparative molecular field analysis
(Topomer CoMFA). A novel U-shape conformation which is distinct from the
literature was demonstrated by molecular docking among 68 U-shape c-met
inhibitors. According to the docking results, two Topomer CoMFA models with high
predictive ability were established based on the two fragment rule. The results
from both docking and topomer CoMFA showed that the pi-pi stacking interaction
with Tyr1230 and the hydrogen bond with hinge region play an important role in
inhibitory activity. Furthermore, the flexible linker and the adjacent solvent
group would be favorable to stabilize the conformation and to enhance the two
interactions mentioned above. Based on our patent, 14 new compounds were designed
by our design strategy. The binding mode exhibited as expected and their
activities were predicted by topomer CoMFA model. The preliminary biological
tests showed most of them have potent activity to c-met kinase. Our study would
provide guidelines to design some new U-shaped c-met inhibitors with new
scaffolds and optimize the current molecules.
PMID- 27486040
TI - Compound Structure-Independent Activity Prediction in High-Dimensional Target
Space.
AB - Profiling of compound libraries against arrays of targets has become an important
approach in pharmaceutical research. The prediction of multi-target compound
activities also represents an attractive task for machine learning with potential
for drug discovery applications. Herein, we have explored activity prediction in
high-dimensional target space. Different types of models were derived to predict
multi-target activities. The models included naive Bayesian (NB) and support
vector machine (SVM) classifiers based upon compound structure information and NB
models derived on the basis of activity profiles, without considering compound
structure. Because the latter approach can be applied to incomplete training data
and principally depends on the feature independence assumption, SVM modeling was
not applicable in this case. Furthermore, iterative hybrid NB models making use
of both activity profiles and compound structure information were built. In high
dimensional target space, NB models utilizing activity profile data were found to
yield more accurate activity predictions than structure-based NB and SVM models
or hybrid models. An in-depth analysis of activity profile-based models revealed
the presence of correlation effects across different targets and rationalized
prediction accuracy. Taken together, the results indicate that activity profile
information can be effectively used to predict the activity of test compounds
against novel targets.
PMID- 27486041
TI - Discovery of Potential, Non-Toxic Influenza Virus Inhibitor by Computational
Techniques.
AB - Influenza infection continues to be a major problem in many parts of the world.
Rimantadine is a first-line drug used to treat the influenza infection by
targeting M2 proton channel. However, S31N mutation in M2 proton channel
diminishes the efficiency of rimantadine and creates resistance. To address this
issue, the present study was aimed to screen the effective lead candidate against
drug resistance strain of influenza from DrugBank database. Initially, the lead
molecules were filtered using Lipinski rule of five and the drug likeliness
property. Subsequently, the data reduction was carried out by employing molecular
docking study. Finally, molecular dynamics simulations techniques were performed
to validate the lead compound. Most importantly, the -p LD50 of the screened lead
molecule was calculated using CORAL software to estimate the Rat oral toxicity.
Accordingly, memantine may possibly become a promising lead compound of
rimantadine-resistant influenza virus strain.
PMID- 27486042
TI - Young-of-the-year fish as a prospective bioindicator for aquatic environmental
contamination monitoring.
AB - Toxic metals (Hg, Cd, Pb) and fifteen perfluoroalkyl substances (PFASs) were
determined in different fish samples at two locations on the Elbe River in the
Czech Republic. The muscle tissue of the two adult fish species most commonly
used as bioindicators in central Europe and whole body homogenates of various
species of young-of-the-year (YOY) fish were used. The purpose of this study was
to evaluate the potential to replace adult fish muscle tissue with YOY fish for
contamination monitoring. All of the toxic metals and five of the fifteen PFASs
were found in the YOY fish samples while only mercury and PFOS were detected in
the muscle tissue of adults. The concentration of total mercury (THg) in the YOY
fish homogenates ranged between 0.014 and 0.062 MUg g(-1). Of the spectrum of
analysed pollutants, only the THg concentrations were lower in YOY fish
homogenates than in adult muscle tissue. The cadmium concentration varied from
0.004 to 0.024 MUg g(-1) and the lead concentration varied from 0.032 to 0.396
MUg g(-1) in YOY fish homogenates, while in most of the adult samples, Cd and Pb
were below the detection limit of the analytical methods employed. The PFOS
concentrations in YOY fish homogenates were comparable to the concentrations
frequently found in adult liver tissue. These results show that mixed shoals of
YOY fish can be successfully used for aquatic bio-monitoring. Interspecific
variability in the concentrations of the target pollutants in YOY fish whole body
homogenates is usually lower than the intraspecific variability of the
concentrations of the pollutants in adult fish muscle. YOY fish were found to be
a suitable bioindicator and have several advantages compared to adult fish.
PMID- 27486043
TI - Occurrence and partitioning of bisphenol analogues in water and sediment from
Liaohe River Basin and Taihu Lake, China.
AB - Bisphenol analogues are widely used in the manufacture of polycarbonate plastics
and epoxy resins, and the demand and production capacity of these compounds are
growing rapidly in China. The occurrence and distribution of bisphenol analogues
other than bisphenol A (BPA) in the aquatic environment is still poorly
understood. In this study, nine bisphenol analogues were measured in water and
sediment samples from Taihu Lake (TL), Liaohe River basin, including Liaohe River
(LR) and Hunhe River (HR), China. Water samples from LR and HR contained much
higher total bisphenols (?BPs) concentrations. BPA and bisphenol S (BPS) were
predominant with a summed contribution of 55, 75, and 75% to the ?BPs in TL, LR,
and HR waters, respectively. This suggests that BPA and BPS were the most widely
used and manufactured bisphenols in these regions. In sediment, BPA was always
predominant, with the next abundant compound bisphenol F (BPF) in TL and HR
sediment, but BPS in LR sediment. The average field sediment-water partitioning
coefficients (log Koc) were calculated for the first time for certain bisphenols
and were determined to be 4.7, 4.6, 3.8, 3.7, and 3.5 mL/g for BPF, BPAP, BPA,
BPAF, and BPS, respectively.
PMID- 27486044
TI - High flux and antifouling properties of negatively charged membrane for dyeing
wastewater treatment by membrane distillation.
AB - This study investigated the applicability of membrane distillation (MD) to treat
dyeing wastewater discharged by the textile industry. Four different dyes
containing methylene blue (MB), crystal violet (CV), acid red 18 (AR18), and acid
yellow 36 (AY36) were tested. Two types of hydrophobic membranes made of
polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) were used. The
membranes were characterized by testing against each dye (foulant-foulant) and
the membrane-dye (membrane-foulant) interfacial interactions and their mechanisms
were identified. The MD membranes possessed negative charges, which facilitated
the treatment of acid and azo dyes of the same charge and showed higher fluxes.
In addition, PTFE membrane reduced the wettability with higher hydrophobicity of
the membrane surface. The PTFE membrane evidenced especially its resistant to dye
absorption, as its strong negative charge and chemical structure caused a flake
like (loose) dye-dye structure to form on the membrane surface rather than in the
membrane pores. This also enabled the recovery of flux and membrane properties by
water flushing (WF), thereby direct-contact MD with PTFE membrane treating 100
mg/L of dye mixtures showed stable flux and superior color removal during five
days operation. Thus, MD shows a potential for stable long-term operation in
conjunction with a simple membrane cleaning process, and its suitability in
dyeing wastewater treatment.
PMID- 27486045
TI - Targeting CDK5 post-stroke provides long-term neuroprotection and rescues
synaptic plasticity.
AB - Post-stroke cognitive impairment is a major cause of long-term neurological
disability. The prevalence of post-stroke cognitive deficits varies between 20%
and 80% depending on brain region, country, and diagnostic criteria. The
biochemical mechanisms underlying post-stroke cognitive impairment are not known
in detail. Cyclin-dependent kinase 5 is involved in neurodegeneration, and its
dysregulation contributes to cognitive disorders and dementia. Here, we
administered cyclin-dependent kinase 5-targeting gene therapy to the right
hippocampus of ischemic rats after transient right middle cerebral artery
occlusion. Cyclin-dependent kinase 5 RNA interference prevented the impairment of
reversal learning four months after ischemia as well as neuronal loss, tauopathy,
and microglial hyperreactivity. Additionally, cyclin-dependent kinase 5 silencing
increased the expression of brain-derived neurotrophic factor in the hippocampus.
Furthermore, deficits in hippocampal long-term potentiation produced by
excitotoxic stimulation were rescued by pharmacological blockade of cyclin
dependent kinase 5. This recovery was blocked by inhibition of the TRKB receptor.
In summary, these findings demonstrate the beneficial impact of cyclin-dependent
kinase 5 reduction in preventing long-term post-ischemic neurodegeneration and
cognitive impairment as well as the role of brain-derived neurotrophic
factor/TRKB in the maintenance of normal synaptic plasticity.
PMID- 27486047
TI - Nonalcoholic steatohepatitis heralding olmesartan-induced sprue-like enteropathy.
PMID- 27486049
TI - Acute pancreatitis: An unusual cause of esophageal stricture.
PMID- 27486048
TI - FOLFOX4 or sorafenib as the first-line treatments for advanced hepatocellular
carcinoma: A cost-effectiveness analysis.
AB - BACKGROUND: This study aimed to investigate the pharmaco-economic implications of
FOLFOX4 or sorafenib for advanced hepatocellular carcinoma in China. METHODS: To
conduct the analysis, we performed a Markov model to simulate the process of
advanced HCC treated with sorafenib or FOLFOX4. Clinical data were obtained from
the ORIENTAL trial and the EACH trial. Incremental cost-effectiveness ratio was
regarded as the primary outcome in the analysis. One-way sensitivity analysis as
well as probabilistic sensitivity analysis was performed to explore the impact of
essential variables on the results of the analysis. RESULTS: Treatment with
sorafenib provided an effectiveness gain of 0.3935 quality-adjusted life year at
an average cost of $18,748.00, whereas chemotherapy of FOLFOX4 brought 0.3808
quality-adjusted life year at a cost of $6876.02. The incremental cost
effectiveness ratio of FOLFOX4 versus sorafenib was $934,801.57/QALY. In a
probabilistic sensitivity analysis based on a Monte Carlo simulation of 1000
items, the probabilities of FOLFOX4 and sorafenib being cost-effective were 100%
and 0% using a willingness-to-pay threshold of $20,301.00 per quality-adjusted
life year. CONCLUSIONS: FOLFOX4 chemotherapy is likely to be a cost-effective
option compared with sorafenib in the treatment of advanced hepatocellular
carcinoma in China.
PMID- 27486050
TI - The power of the patient question: A secret shopper study.
AB - OBJECTIVES: To examine the effect of one standardized patient question on the
length, number and type of new topics pharmacists addressed. To explore how
community pharmacists counsel secret shoppers on two types of over-the-counter
(OTC) medications-ibuprofen (IB) and emergency contraceptives (EC). METHODS: 25
pharmacists from 7 independent, midwestern community pharmacies consented to have
secret shoppers purchase an OTC medication and to have their consultations audio
recorded. Following standardized scenarios, 5 secret shoppers audio-recorded 73
encounters. At the end of 36 encounters secret shoppers asked one standard
question, "What else should I know before taking this product?" Role Theory
informed the study design with apriori hypotheses that topics assessed, topics
discussed, and consultation length would vary by the OTC medication (IB or EC)
and whether secret shoppers asked a question. Audio-recording coding had high
inter-rater reliability (kappa=0.94). RESULTS: Length of encounter was
significantly associated with patients asking the question (p<0.05), but not type
of OTC medication. On average 1.22 new topics were discussed with a patient
question. New topics included information about safe and efficacious use of the
OTC's. CONCLUSION: Results highlight the importance of encouraging patients to
ask pharmacists their questions about OTC products for safe use and thorough
consultations.
PMID- 27486051
TI - Evaluation of individualized quality of life and illness perceptions in low back
pain. A patient education cluster randomized controlled trial.
AB - OBJECTIVE: To evaluate the effect of a cognitive patient education intervention
compared with usual care on secondary outcomes of individual quality of life and
psychological outcomes of illness perceptions and pain catastrophizing in
patients with low back pain. METHODS: A pragmatic cluster randomized controlled
trial in which 16 general practitioners (GPs) and 20 physiotherapists (PTs) in
primary care were randomly assigned to provide either a cognitive patient
education intervention or usual treatment. Patients were followed up at 4 weeks
and 12 months after treatment. Linear mixed models were used with group, time,
type of clinician and interaction effects of group*time as fixed effects.
RESULTS: A total of 203 patients provided data at baseline, 86% responded at 4
weeks and 74% at 12 months. For all the outcome measures there was a
statistically significant effect of time (p<0.001) and type of clinician (p<0.05)
during the follow-up year. There was a significant interaction effect of
group*time on illness perceptions (p=0.003), however not for the other outcome
measures. CONCLUSION: The cognitive patient education intervention initiated a
faster improvement in illness perceptions but not in the other outcomes. PRACTICE
IMPLICATIONS: A patient education intervention can be beneficial to improve
illness perceptions, however more research is needed.
PMID- 27486046
TI - Inflammasomes link vascular disease with neuroinflammation and brain disorders.
AB - The role of inflammation in neurological disorders is increasingly recognised.
Inflammatory processes are associated with the aetiology and clinical progression
of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia
and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both
central and systemic inflammatory actions have been linked with the development
of brain diseases, suggesting that complex neuro-immune interactions could
contribute to pathological changes in the brain across multiple temporal and
spatial scales. However, the mechanisms through which inflammation impacts on
neurological disease are improperly defined. To develop effective therapeutic
approaches, it is imperative to understand how detrimental inflammatory processes
could be blocked selectively, or controlled for prolonged periods, without
compromising essential immune defence mechanisms. Increasing evidence indicates
that common risk factors for brain disorders, such as atherosclerosis, diabetes,
hypertension, obesity or infection involve the activation of NLRP3, NLRP1, NLRC4
or AIM2 inflammasomes, which are also associated with various neurological
diseases. This review focuses on the mechanisms whereby inflammasomes, which
integrate diverse inflammatory signals in response to pathogen-driven stimuli,
tissue injury or metabolic alterations in multiple cell types and different
organs of the body, could functionally link vascular- and neurological diseases
and hence represent a promising therapeutic target.
PMID- 27486052
TI - Shared decision making within goal setting in rehabilitation settings: A
systematic review.
AB - OBJECTIVE: To map out and synthesise literature that considers the extent of
shared decision-making (SDM) within goal-setting in rehabilitation settings and
explore participants' views of this approach within goal-setting. METHODS: Four
databases were systematically searched between January 2005-September 2015. All
articles addressing SDM within goal-setting involving adult rehabilitation
patients were included. The literature was critically appraised followed by a
thematic synthesis. RESULTS: The search output identified 3129 studies and 15
articles met the inclusion criteria. Themes that emerged related to methods of
SDM within goal-setting, participants' views on SDM, perceived benefits of SDM,
barriers and facilitators to using SDM and suggestions to improve involvement of
patients resulting in a better process of goal-setting. CONCLUSIONS: The
literature showed various levels of patient involvement existing within goal
setting however few teams adopted an entirely patient-centred approach. However,
since the review has identified clear value to consider SDM within goal-setting
for rehabilitation, further research is required and practice should consider
educating both clinicians and patients about this approach. PRACTICE
IMPLICATIONS: To enhance the use of SDM within goal-setting in rehabilitation it
is likely clinicians and patients will require further education on this
approach. For clinicians this could commence during their training at
undergraduate level.
PMID- 27486053
TI - Functional Vegetable Guar (Cyamopsis tetragonoloba L. Taub.) Accessions for
Improving Flavonoid Concentrations in Immature Pods.
AB - Dry guar (Cyamopsis tetragonoloba L. Taub) seeds are primarily used to extract
galactomannan gum for oil fracking, however, the immature pods are used as a
vegetable in India and sold in ethnic grocery stores in the Atlanta, Georgia
area. Nineteen guar genotypes were grown in the field at Griffin, GA, USA for two
years (2010-2011). Since the determination of flavonoid concentration would add
value to the guar accessions for use as a functional food vegetable, immature
guar pods were evaluated for flavonoid concentration. In this study, the immature
pods from these 19 guar accessions were analyzed for flavonoid concentration
using high-performance liquid chromatography. Several accessions including PI
253182, PI 262152, PI 263698, and PI 288357 showed significantly greater daidzein
concentration than all three controls based on seed production in 2010. However,
PI 179926, PI 180434, PI 182969, PI 183400, PI 253182, PI 262152, PI 263882, and
PI 263897 exhibited significantly greater genistein concentration than the second
and third best controls in 2011. Both PI 180434 and PI 288359 produced
significantly higher kaempferol concentration than the third best control.
Daidzein concentration was significantly correlated with genistein concentration
(r2 = 0.47*) for both years. Luteolin concentration showed a significant negative
correlation with genistein (r2 = -0.45*). Quercetin concentration significantly
correlated with kaempferol (r2 = 0.854***) and genistein (r2 = 0.455*)
concentrations. The accession, PI 542608 was observed to contain high
concentrations of kaempferol and quercetin in the cluster analyses. These results
will help plant breeders develop guar cultivars with superior flavonoid
concentrations.
PMID- 27486055
TI - Five (bad) reasons to publish your research in predatory journals.
PMID- 27486054
TI - Sphingosine-1-phosphate-enhanced Wnt5a promotes osteogenic differentiation in
C3H10T1/2 cells.
AB - In this study, we investigated the involvement of Wnt signaling in sphingosine-1
phosphate (S1P)-enhanced osteogenic differentiation of C3H10T1/2 pluripotent stem
cells. We found that S1P enhanced the expression of Wnt5a and low-density
lipoprotein receptor-related protein 5 or 6 (LRP5/6) during osteogenic
differentiation. Wnt5a-neutralizing antibody inhibited S1P-enhanced expression of
LRP5/6 and alkaline phosphatase, which are essential for osteogenic
differentiation. Conversely, S1P did not affect endogenous canonical Wnt
signaling. Taken together, S1P-enhanced Wnt5a promotes LRP5/6 expression,
resulting in the trigger of osteogenic differentiation of C3H10T1/2 cells. These
findings suggest a potential beneficial role for S1P in bone regeneration.
PMID- 27486056
TI - Olfactory Dysfunction in IgG4-Related Disease.
AB - IgG4-related disease is a newly recognized systemic disease, and its elucidation
is progressing. However, little is known about its sinonasal manifestations. The
aim of this study was to assess the olfaction of patients with IgG4-related
disease. Twenty-five patients with IgG4-related disease underwent T&T
olfactometry to measure olfactory function. We analyzed the clinical features,
including serum IgG4 and IgE levels, involved organs, and sinonasal computed
tomography scores to explore the etiology of olfactory dysfunction. Thirteen
patients with IgG4-related disease were found to have moderate to severe
olfactory dysfunction (52%). There were no differences in the clinical features
between the olfactory dysfunction group and the normal group. In 7 patients, the
inferior turbinate was biopsied to study the correlation between olfaction score
and the number of IgG4-positive cells, but no such correlation was found. Six
hyposmia patients recovered to a normal state. Five patients recovered after
corticosteroid treatment and 1 recovered spontaneously. We found that the
prevalence of olfactory dysfunction was high in patients with IgG4-related
disease and that it could be reversed. Olfactory dysfunction appears to be a
novel important manifestation of IgG4-related disease.
PMID- 27486057
TI - Neutrons in proton pencil beam scanning: parameterization of energy, quality
factors and RBE.
AB - The biological effectiveness of neutrons produced during proton therapy in
inducing cancer is unknown, but potentially large. In particular, since neutron
biological effectiveness is energy dependent, it is necessary to estimate,
besides the dose, also the energy spectra, in order to obtain quantities which
could be a measure of the biological effectiveness and test current models and
new approaches against epidemiological studies on cancer induction after proton
therapy. For patients treated with proton pencil beam scanning, this work aims to
predict the spatially localized neutron energies, the effective quality factor,
the weighting factor according to ICRP, and two RBE values, the first obtained
from the saturation corrected dose mean lineal energy and the second from DSB
cluster induction. A proton pencil beam was Monte Carlo simulated using GEANT.
Based on the simulated neutron spectra for three different proton beam energies a
parameterization of energy, quality factors and RBE was calculated. The pencil
beam algorithm used for treatment planning at PSI has been extended using the
developed parameterizations in order to calculate the spatially localized neutron
energy, quality factors and RBE for each treated patient. The parameterization
represents the simple quantification of neutron energy in two energy bins and the
quality factors and RBE with a satisfying precision up to 85 cm away from the
proton pencil beam when compared to the results based on 3D Monte Carlo
simulations. The root mean square error of the energy estimate between Monte
Carlo simulation based results and the parameterization is 3.9%. For the quality
factors and RBE estimates it is smaller than 0.9%. The model was successfully
integrated into the PSI treatment planning system. It was found that the
parameterizations for neutron energy, quality factors and RBE were independent of
proton energy in the investigated energy range of interest for proton therapy.
The pencil beam algorithm has been extended using the developed parameterizations
in order to calculate the neutron energy, quality factor and RBE.
PMID- 27486059
TI - Direct Catalytic Asymmetric Mannich Reaction with Dithiomalonates as Excellent
Mannich Donors: Organocatalytic Synthesis of (R)-Sitagliptin.
AB - In this study, dithiomalonates (DTMs) were demonstrated to be exceptionally
efficient Mannich donors in terms of reactivity and stereoselectivity in cinchona
based-squaramide-catalyzed enantioselective Mannich reactions of diverse imines
or alpha-amidosulfones as imine surrogates. Owing to the superior reactivity of
DTMs as compared to conventional malonates, the catalyst loading could be reduced
to 0.1 mol % without the erosion of enantioselectivity (up to 99 % ee).
Furthermore, by the use of a DTM, even some highly challenging primary alkyl
alpha-amidosulfones were smoothly converted into the desired adducts with
excellent enantioselectivity (up to 97 % ee), whereas the use of a malonate or
monothiomalonate resulted in no reaction under identical conditions. The
synthetic utility of the chiral Mannich adducts obtained from primary alkyl
substrates was highlighted by the organocatalytic, coupling-reagent-free
synthesis of the antidiabetic drug (-)-(R)-sitagliptin.
PMID- 27486058
TI - The pro-oxidant gene p66shc increases nicotine exposure-induced lipotoxic
oxidative stress in renal proximal tubule cells.
AB - Nicotine (NIC) exposure augments free fatty acid (FFA) deposition and oxidative
stress, with a concomitant increase in the expression of the pro-oxidant p66shc.
In addition, a decrease in the antioxidant manganese superoxide dismutase (MnSOD)
has been observed in the kidneys of mice fed a high-fat diet. The present study
aimed to determine whether the pro-oxidant p66shc mediates NIC-dependent
increases in renal oxidative stress by augmenting the production of reactive
oxygen species (ROS) and suppressing the FFA-induced antioxidant response in
cultured NRK52E renal proximal tubule cells. Briefly, NRK52E renal proximal
tubule cells were treated with 200 uM NIC, 100 uM oleic acid (OA), or a
combination of NIC and OA. The expression levels of p66shc and MnSOD were
modulated according to genetic methods. ROS production and cell injury, in the
form of lactate dehydrogenase release, were subsequently detected. Promoter
activity of p66shc and MnSOD, as well as forkhead box (FOXO)-dependent
transcription, was investigated using reporter luciferase assays. The results
demonstrated that NIC exacerbated OA-mediated intracellular ROS production and
cell injury through the transcriptional activation of p66shc. NIC also suppressed
OA-mediated induction of the antioxidant MnSOD promoter activity through p66shc
dependent inactivation of FOXO activity. Overexpression of p66shc and knockdown
of MnSOD had the same effect as treatment with NIC on OA-mediated lipotoxicity.
These data may be used to generate a therapeutic means to ameliorate renal
lipotoxicity in obese smokers.
PMID- 27486060
TI - Efficacy and safety of point-of-care ultrasound-guided intra-articular
corticosteroid joint injections in patients with haemophilic arthropathy.
AB - INTRODUCTION AND OBJECTIVES: Intra-articular corticosteroid injections are
standard of care for managing joint pain secondary to osteoarthritis or
rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have
introduced and evaluated the efficacy and safety of ultrasound-guided
corticosteroid injections for pain relief in patients with haemophilic
arthropathy. PATIENTS AND METHODS: Ultrasound-guided intra-articular injections
performed on haemophilia patients at UCSD between March 2012 and January 2016
were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL
lidocaine) were performed with musculoskeletal ultrasound and Power Doppler.
Analysis included patient demographics, joint-specific parameters such as tissue
hypervascularity and effusions, pain relief, and procedure-associated
complications. RESULTS: Forty-five injections (14 ankles, 13 elbows, 18 knees)
were administered in 25 patients. Advanced arthropathy with hypervascularity
and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one
per cent of injections resulted in pain relief which was significant in 84% (>30%
reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001),
usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16
weeks). Haemophilia B patients experienced longer periods of relief, and high
Pettersson scores were associated with shorter duration of relief. There were no
procedure-associated complications. Repeat ultrasound of eight joints within 4
weeks of injection demonstrated nearly complete resolution of hypervascularity.
CONCLUSIONS: Point-of-care ultrasound enabled intra-articular corticosteroid
injections that provided highly effective, safe, and relatively long-lasting pain
relief in haemophilic arthropathy. This approach should be used to improve pain
management in haemophilic arthropathy.
PMID- 27486061
TI - Extended-Spectrum beta-lactam Resistance in the Enteric Flora of Patients at a
Tertiary Care Medical Centre.
AB - The dissemination of Enterobacteriaceae expressing resistance to extended
spectrum cephalosporins, which are therapeutically used in both human and
veterinary medicine, is of critical concern. The normal commensal flora of food
animals may serve as an important reservoir for the zoonotic food-borne
transmission of Enterobacteriaceae harbouring beta-lactam resistance. We
hypothesized that the predominant AmpC and ESBL genes reported in US livestock
and fresh retail meat products, blaCMY-2 and blaCTX-M , would also be predominant
in human enteric flora. We recovered enteric flora from a convenience sample of
patients included in a large tertiary medical centre's Clostridium difficile
surveillance programme to screen for and estimate the frequency of carriage of
AmpC and ESBL resistance genes. In- and outpatient diarrhoeic submissions (n =
692) received for C. difficile testing at the medical centre's clinical
diagnostic laboratory from July to December, 2013, were included. Aliquoted to a
transport swab, each submission was inoculated to MacConkey broth with
cefotaxime, incubated at 37 degrees C and then inoculated to MacConkey agars
supplemented with cefoxitin and cefepime to select for the AmpC and ESBL
phenotypes, with blaCMY and blaCTX-M genotypes confirmed by PCR and sequencing.
From the 692 diarrhoeic submissions, our selective culture yielded 184 isolates
(26.6%) with reduced susceptibility to cefotaxime. Of these, 46 (6.7%) samples
harboured commensal isolates carrying the AmpC blaCMY . Another 21 (3.0%) samples
produced isolates harbouring the ESBL blaCTX-M : 19 carrying CTX-M-15 and 2 with
CTX-M-27. Our results indicate that beta-lactam resistance genes likely acquired
through zoonotic food-borne transmission are present in the enteric flora of this
hospital-associated population at lower levels than reported in livestock and
fresh food products.
PMID- 27486063
TI - Plasma functionalization procedure for antibody immobilization for SU-8 based
sensor.
AB - In this paper, we report the study on a new protocol for the immobilization
process of antigen/antibody assay on SU-8 layers by oxygen plasma treatment.
Plasma treatments, at different plasma powers and for different duration times,
are performed and their effects on immobilization efficiency are studied. The
chemical properties and the surface morphology of SU-8 before and after the
functionalization and immobilization of (IgG) are then verified by Raman
spectroscopy and atomic force microscopy (AFM). An increase of the surface
roughness of SU-8 layers is observed after the oxygen plasma treatment and an
intensity variation of functional groups is also evidenced. To demonstrate the
validity of the process the distribution of IgG immobilized on SU-8 surfaces is
detected by fluorescence microscopy measurement after incubation with fluorescein
isothiocyanate (FITC)-tagged anti-human IgG. An increase of the amount of the
adsorbed protein of about 20% and a good repeatability on antigen/antibody
distribution on the surface are detected for IgG on plasma treated substrates.
Finally, label free measurements are performed by SU-8 optical ring resonators
reaching detection limits of 0.86ngcm(-2). The proposed approach offers a smart
protocol for IgG immobilization on SU-8 substrate that can be easily extended to
different antigen/antibody assay and polymeric materials for the realization of
high performance immunosensors.
PMID- 27486062
TI - TLE4 regulation of wnt-mediated inflammation underlies its role as a tumor
suppressor in myeloid leukemia.
AB - The presence of AML1-ETO (RUNX1-CBF2T1), a fusion oncoprotein resulting from a
t(8;21) chromosomal translocation, has been implicated as a necessary but
insufficient event in the development of a subset of acute myeloid leukemias
(AML). While AML1-ETO prolongs survival and inhibits differentiation of
hematopoietic stem cells (HSC), other contributory events are needed for cell
proliferation and leukemogenesis. We have postulated that specific tumor
suppressor genes keep the leukemic potential of AML1-ETO in check. In studying
del(9q), one of the most common concomitant chromosomal abnormalities with
t(8;21), we identified the loss of an apparent tumor suppressor, TLE4, that
appears to cooperate with AML1-ETO to confer a leukemic phenotype. This study
sought to identify the molecular basis of this cooperation. We show that the loss
of TLE4 confers proliferative advantage to leukemic cells, simultaneous with an
upregulation of a pro- inflammatory signature mediated through aberrant increases
in Wnt signaling activity. We further demonstrate that inhibition of
cyclooxygenase (COX) activity partly reverses the pro-leukemic phenotype due to
TLE4 knockdown, pointing towards a novel therapeutic approach for myeloid
leukemia.
PMID- 27486064
TI - Pharmacists caring for transgender persons.
PMID- 27486065
TI - Ambiguity: A new way of thinking about responses to climate change.
AB - Diversity, interdisciplinarity and transdisciplinarity are now recognized as
vital to tackling wicked problems such as those presented by a changing climate
(Nature editorial 2015, Ledford 2015; Dick et al., 2016). Including diverse
disciplines in science projects enables a range of different views which often
facilitate the creation of innovative solutions. Supporting multiple views and
options requires a different way of working beyond traditional reductionist
approaches to science, communication and decision-making. To embrace diversity in
scientific project teams in order to tackle complex, integrated and urgent issues
but to expect singular and linear pathways forward is paradoxical. Much has been
written about the need for the scientific community to embrace uncertainty (e.g.
Popper, Lempert & Bankes 2005; Lempert et al., 2004; Nelson, Howden & Hayman
2013; Bammer & Smithson 2008). We argue that this in itself will not suffice, and
that there is also a need to embrace ambiguity in certain situations. Thus, in
this article we explore: (1) what ambiguity is, including the benefits it can
offer to climate adaptation in particular, using existing approaches to ambiguity
in the arts and humanities as examples (2), we discuss practical meanings of
ambiguity in relation to climate change, (3) we propose possible next steps for
bringing ambiguity into interdisciplinary practice, and (4) we identify some
challenges and necessary preconditions to successfully and appropriately
embracing ambiguity.
PMID- 27486066
TI - Fungus-associated bacteriome in charge of their host behavior.
AB - Bacterial-fungal interactions are widespread in nature and there is a growing
number of studies reporting distinct fungus-associated bacteria. However, little
is known so far about how shifts in the fungus-associated bacteriome will affect
the fungal host's lifestyle. In the present study, we describe for the first time
the bacterial community associated with the saprotrophic fungus Mucor hiemalis,
commonly found in soil and rhizosphere. Two broad-spectrum antibiotics that
strongly altered the bacterial community associated with the fungus were applied.
Our results revealed that the antibiotic treatment did not significantly reduce
the amount of bacteria associated to the fungus but rather changed the community
composition by shifting from initially dominating Alpha-Proteobacteria to
dominance of Gamma-Proteobacteria. A novel approach was applied for the isolation
of fungal-associated bacteria which also revealed differences between bacterial
isolates obtained from the original and the antibiotic-treated M. hiemalis. The
shift in the composition of the fungal-associated bacterial community led to
significantly reduced fungal growth, changes in fungal morphology, behavior and
secondary-metabolites production. Furthermore, our results showed that the
antibiotic-treated isolate was more attractive and susceptible to mycophagous
bacteria as compared to the original isolate. Overall, our study highlights the
importance of the fungus-associated bacteriome for the host's lifestyle and
interactions and indicate that isolation with antibacterials is not sufficient to
eradicate the associated bacteria.
PMID- 27486067
TI - Three alcohol dehydrogenase genes and one acetyl-CoA synthetase gene are
responsible for ethanol utilization in Yarrowia lipolytica.
AB - The non-conventional yeast Yarrowia lipolytica is able to utilize a wide range of
different substrates like glucose, glycerol, ethanol, acetate, proteins and
various hydrophobic molecules. Although most metabolic pathways for the
utilization of these substrates have been clarified by now, it was not clear
whether ethanol is oxidized by alcohol dehydrogenases or by an alternative
oxidation system inside the cell. In order to detect the genes that are required
for ethanol utilization in Y. lipolytica, eight alcohol dehydrogenase (ADH) genes
and one alcohol oxidase gene (FAO1) have been identified and respective deletion
strains were tested for their ability to metabolize ethanol. As a result of this,
we found that the availability of ADH1, ADH2 or ADH3 is required for ethanol
utilization in Y. lipolytica. A strain with deletions in all three genes is
lacking the ability to utilize ethanol as sole carbon source. Although Adh2p
showed by far the highest enzyme activity in an in vitro assay, the availability
of any of the three genes was sufficient to enable a decent growth. In addition
to ADH1, ADH2 and ADH3, an acetyl-CoA synthetase encoding gene (ACS1) was found
to be essential for ethanol utilization. As Y. lipolytica is a non-fermenting
yeast, it is neither able to grow under anaerobic conditions nor to produce
ethanol. To investigate whether Y. lipolytica may produce ethanol, the key genes
of alcoholic fermentation in S. cerevisiae, ScADH1 and ScPDC1, were overexpressed
in an ADH and an ACS1 deletion strain. However, instead of producing ethanol, the
respective strains regained the ability to use ethanol as single carbon source
and were still not able to grow under anaerobic conditions.
PMID- 27486068
TI - Ultrashort cationic lipopeptides and lipopeptoids: Evaluation and mechanistic
insights against epithelial cancer cells.
AB - Peptides present an attractive scaffold for the development of new anticancer
lead agents due to their accessibility and ease of modification. Synthetic
ultrashort cationic lipopeptides, with four amino acids or less conjugated to a
fatty acid, were developed to retain the biological activity of longer peptides
in a smaller molecular size. Herein, we report the activity of amphiphilic
lipotripeptides, lipotripeptoids and lipotetrapeptides against breast (MDA-MB
231, JIMT-1), prostate (DU145) and pancreas (MiaPaCa2) epithelial cancer cell
lines. The lipotripeptide C16-KKK-NH2 and lipotetrapeptide C16-PCatPHexPHexPCat
NH2 were identified to possess anticancer activity. The latter lipotetrapeptide
possess a short polyproline scaffold consisting of only two L-4R-aminoproline
(PCat) and two L-4R-hexyloxyproline (PHex). However, all the prepared
lipotripeptoids lack anticancer activity. The amphiphilic C16-PCatPHexPHexPCat
NH2 exhibited similar anticancer potency to the surfactant benzethonium chloride
while superior activity was observed in comparison to myristylamine. Mechanistic
studies revealed that the peptides do not lyse ovine erythrocytes nor epithelial
cancer cells, thus ruling out necrosis as the mechanism of cell death.
Surprisingly, the two lipopeptides exhibit different mechanisms of action that
result in cancer cell death. The lipotripeptide C16-KKK-NH2 was found to induce
caspase-mediated apoptosis while C16-PCatPHexPHexPCat-NH2 kills tumor cells
independent of caspases.
PMID- 27486069
TI - p21(CIP1/WAF1)-dependent inhibition of cardiac hypertrophy in response to
Angiotensin II involves Akt/Myc and pRb signaling.
AB - The cyclin-dependent kinase inhibitor p21(CIP1/WAF1) (p21) is highly expressed in
the adult heart. However, in response to stress, its expression is downregulated.
Therefore, we investigated the role of p21 in the regulation of cardiac
hypertrophic growth. At 2 months of age, p21 knockout mice (p21KO) lack an overt
cardiac phenotype. In contrast, by 10 months of age, p21KO developed age
dependent cardiac hypertrophy and heart failure. After 3 weeks of trans-aortic
banding (TAB), the heart/body weight ratio in 11 week old p21KO mice increased by
57%, as compared to 42% in wild type mice indicating that p21KO have a higher
susceptibility to pressure overload-induced cardiac hypertrophy. We then
chronically infused 8 week old wild type mice with Angiotensin II (2.0mg/kg/min)
or saline subcutaneously by osmotic pumps for 14 days. Recombinant TAT conjugated
p21 protein variants (10mg/kg body weight) or saline were intraperitoneally
injected once daily for 14 days into Angiotensin II and saline-infused animals.
Angiotensin II treated mice developed pathological cardiac hypertrophy with an
average increase of 38% in heart/body weight ratios, as compared to saline
treated controls. Reconstitution of p21 function by TAT.p21 protein transduction
prevented Angiotensin II-dependent development of cardiac hypertrophy and
failure. Taken together, our genetic and biochemical data show an important
function of p21 in the regulation of growth-related processes in the heart.
PMID- 27486070
TI - Effects of increasing levothyroxine on pregnancy outcomes in women with
uncontrolled hypothyroidism.
AB - OBJECTIVE: Uncontrolled hypothyroidism has been associated with an increased risk
of adverse pregnancy outcomes. We aimed to assess the effectiveness of increasing
levothyroxine (LT4) dose on reducing the risk of adverse outcomes for pregnant
women with TSH level greater than the recommended 1st trimester limit. DESIGN,
PATIENTS, MEASUREMENTS: We reviewed the electronic medical records of pregnant
women evaluated from January 2011 to December 2013, who had history of LT4
treated hypothyroidism and were found to have TSH > 2.5 mIU/l in 1st trimester.
Women were divided into two groups: group A - LT4 dose was increased within two
weeks from the TSH test, group B - LT4 dose remained stable. We compared the
frequency of pregnancy loss (primary outcome) and other prespecified pregnancy
related adverse outcomes between groups. RESULTS: There were 85 women in group A
(median TSH: 5.0, interquartile range 3.8-6.8 mIU/l) and 11 women in group B
(median TSH: 4.5, interquartile range 3.2-4.9 mIU/l). The groups were not
different in baseline clinical and socioeconomic characteristics. The mean
interval between TSH test and LT4 dose increase was 4.5 (SD 4.6) days. Pregnancy
loss was significantly lower in group A (2/85, 2.4%) vs group B (4/11, 36.4%) (P
= 0.001). Other pregnancy-related adverse outcomes were similar between groups.
CONCLUSIONS: Increasing LT4 dose for women with uncontrolled hypothyroidism in
the 1st trimester of pregnancy was associated with a decreased risk of pregnancy
loss. Given the limitations of our study, this association awaits further
confirmation from larger studies.
PMID- 27486071
TI - Semen characteristics and biochemical composition of cloacal foam of male
Japanese quails (Coturnix coturnix Japonica) fed diet incorporated with selenium.
AB - An attempt was made to investigate the effect of dietary selenium (Se) on
physical and cloacal gland size, foam production, biochemical composition of foam
and semen biochemical characteristics of male Japanese quail (Coturnix coturnix
Japonica). Two hundred twenty-five (225)-day-old male Japanese quail were
randomly distributed to three dietary treatment groups for a period of 20 weeks.
Each treatment comprised of three replicates, each containing 25 chicks. Three
experimental diets were supplemented with 0, 0.5 and 1.0 mg Se/kg (T1 , T2 and
T3, respectively), and diet T1 was considered as control. Sodium selenite was
used as the source of selenium. All the birds were provided with feed and water
ad libitum. Cloacal foam characteristics, that is cloacal gland index and foam
weight, were significantly higher in T2 group. However, body weight, frequency of
foam discharge and testes weight (left and right) did not differ significantly (p
> 0.05). Physical characteristics of semen, that is semen volume and sperm
concentration, did not differ (p > 0.05) among the Se-treated groups. The sperm
motility, live-dead count and abnormality improved significantly (p < 0.05) in
0.5 mg/Se-supplemented group compared to 0 or 1.0 mg/Se-supplemented groups.
Similarly, fertility and hatchability percentages were higher (p < 0.05) in 0.5
mg/Se-supplemented group than in control or 1.0 mg/Se-supplemented counterparts.
The biochemical characteristics of foam in terms of total protein, acid
phosphatase (ACP) and nitric oxide did not differ (p > 0.05), while the
concentration of glucose was higher (p < 0.05) in 0.5 mg/Se-supplemented diet. On
the other hand, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and
aspartate aminotransferase (AST) were lower (p < 0.05) in 0.5 mg/Se-supplemented
group compared to control or 1.0 mg/Se-supplemented groups. From this study, it
was concluded that supplementation of 0.5 mg Se/kg diet was beneficial for foam
variables, biochemical composition of foam, semen characteristics and fertility
in male Japanese quail.
PMID- 27486072
TI - Prenatal diagnosis of double aortic arch: can we predict airway obstruction
(pseudo-CHAOS) and need for airway EXIT?
PMID- 27486073
TI - Two-step crystal growth mechanism during crystallization of an undercooled
Ni50Al50 alloy.
AB - Crystallization processes are always accompanied by the emergence of multiple
intermediate states, of which the structures and transition dynamics are far from
clarity, since it is difficult to experimentally observe the microscopic pathway.
To insight the structural evolution and the crystallization dynamics, we perform
large-scale molecular dynamics simulations to investigate the time-dependent
crystallization behavior of the NiAl intermetallic upon rapid solidification. The
simulation results reveal that the crystallization process occurs via a two-step
growth mechanism, involving the formation of initial non-equilibrium long range
order (NLRO) regions and of the subsequent equilibrium long range order (ELRO)
regions. The formation of the NLRO regions makes the grains rather inhomogeneous,
while the rearrangement of the NLRO regions into the ELRO regions makes the
grains more ordered and compact. This two-step growth mechanism is actually
controlled by the evolution of the coordination polyhedra, which are
characterized predominantly by the transformation from five-fold symmetry to four
fold and six-fold symmetry. From liquids to NLRO and further to ELRO, the five
fold symmetry of these polyhedra gradually fades, and finally vanishes when B2
structure is distributed throughout the grain bulk. The energy decrease along the
pathway further implies the reliability of the proposed crystallization
processes.
PMID- 27486074
TI - Direct-geneFISH: tuning up microscopic and molecular methodologies for targeted
cell visualization.
PMID- 27486075
TI - The host specificity of ape malaria parasites can be broken in confined
environments.
AB - Recent studies have revealed a large diversity of Plasmodium spp. among African
great apes. Some of these species are related to Plasmodium falciparum, the most
virulent agent of human malaria (subgenus Laverania), and others to Plasmodium
ovale, Plasmodium malariae and Plasmodium vivax (subgenus Plasmodium), three
other human malaria agents. Laverania parasites exhibit strict host specificity
in their natural environment. Plasmodium reichenowi, Plasmodium billcollinsi,
Plasmodium billbrayi and Plasmodium gaboni infect only chimpanzees, while
Plasmodium praefalciparum, Plasmodium blacklocki and Plasmodium adleri are
restricted to gorillas and Plasmodium falciparum is pandemic in humans. This host
specificity may be due to genetic and/or environmental factors. Infrastructures
hosting captive primates, such as sanctuaries and health centres, usually
concentrate different primate species, thus favouring pathogen exchanges. Using
molecular tools, we analysed blood samples from captive non-human primates living
in Gabon to evaluate the risk of Plasmodium spp. transfers between host species.
We also included blood samples from workers taking care of primates to assess
whether primate-human parasite transfers occurred. We detected four transfers of
Plasmodium from gorillas towards chimpanzees, one from chimpanzees to gorillas,
three from humans towards chimpanzees and one from humans to mandrills. No simian
Plasmodium was found in the blood samples from humans working with primates.
These findings demonstrate that the genetic barrier that determines the apparent
host specificity of Laverania is not completely impermeable and that parasite
exchanges between gorillas and chimpanzees are possible in confined environments.
PMID- 27486077
TI - Streamlining ethical review of data intensive research.
PMID- 27486076
TI - Protein aggregation and neurodegenerative diseases: From theory to therapy.
AB - The study of protein misfolding and aggregation saw resurgence in the last
decade. Aggregation is the main cause of several human neurodegenerative diseases
which makes this field as the leading edge in the science today. Protein
aggregation is a highly complex process resulting in formation of a variety of
aggregates with different structures and morphologies. Many of them are highly
cytotoxic. In-depth knowledge about structure, mechanism of formation, and
physiological effects of aggregates will shed new light on the aggregation
mediated cell toxicity, and helps in deciphering new target for drug design and
development. This review summarizes the existing information on the molecular
mechanism of protein misfolding and aggregation involved in neurodegeneration
stressing on the possible therapeutic intervention in neurodegenerative diseases.
As our knowledge about the relation between the protein misfolding and disease
pathogenesis will be enhanced, more specific and promising treatment
opportunities will come into existence.
PMID- 27486078
TI - Predicting Novel Antitumor Agents: 3D-Pharmacophore Mapping of beta-N-biaryl
Ether Sulfonamide-Based Hydroxamates as Potentially MMP-2 Inhibitors.
AB - Matrix metalloproteinases (MMP) are a group of enzymes related to extracelular
matrix remodeling. Some types of MMP are overexpressed by malignant tumors,
mainly the MMP-2 subtype, and have been associated to cancer invasiveness and
metastasis. A receptor-independent (RI) 4D-QSAR formalism was applied, herein, to
a set of forty beta-N-biaryl ether sulfonamide hydroxamates, previously reported
as potent MMP-2 inhibitors, in order to map 3D-pharmacophore models and predict
novel antitumor agents. The best RI 4D-QSAR model was statistically significant
(N=30, r(2) =0.93, q(2) =0.88, five occupancy descriptors (GCOD), LSE=0.04,
LOF=0.11, outliers=0), robust and not obtained by chance. The external
predictability was 75 % (test set; N=8). A different orientation (binding mode)
in the MMP-2 catalytic site was suggested regarding the most hydrophobic portion
(R1 ) of the compounds' structure. Compounds were predicted and their inhibitory
activity against MMP-2 was calculated by using the optimum RI 4D-QSAR model. The
findings have provided interesting information to drive the designing and
synthesis of novel potentially MMP-2 inhibitors against melanoma invasion.
PMID- 27486079
TI - Discovery of Novel Mycobacterial DNA Gyrase B Inhibitors: In Silico and In Vitro
Biological Evaluation.
AB - DNA gyrase of Mycobacterium tuberculosis (MTB) is a type II topoisomerase that
ensures the regulation of DNA topology and has been genetically demonstrated to
be a bactericidal drug target. Availability of crystal structure of M. smegmatics
GyrB in complex with one of the aminopyrazinamides facilitated us to employ
structure-based virtual screening approach to obtain new hits from a commercial
library of Asinex database using energy-optimized pharmacophore modeling. Further
the model was validated using enrichment calculations, and finally three models
were employed for high-throughput virtual screening and docking to identify novel
DNA gyrase B inhibitors. This study led to the identification of fifteen
potential compounds with IC50 values in the range of 1.5-45.5 uM against M.
smegmatics GyrB and 1.16-25 uM in MTB supercoiling assay. Lead 11 emerged as the
most potential compound, exhibiting inhibition of MTB DNA gyrase supercoiling
with an IC50 of 1.16+/-0.25 uM, and M. smegmatics GyrB IC50 of 1.5+/-0.12 uM and
hence could be further developed as novel inhibitor for mycobacterial GyrB.
PMID- 27486080
TI - Pharmacophore Modeling, Ensemble Docking, Virtual Screening, and Biological
Evaluation on Glycogen Synthase Kinase-3beta.
AB - Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine protein
kinase which is engaged in a variety of signaling pathways, regulating a wide
range of cellular processes. GSK-3beta, also known as tau protein kinase I (TPK
I), is one of the most important kinases implicated in the hyperphosphorylation
of tau that leads to neurodegenerative diseases. Hence, GSK-3beta has emerged as
an important therapeutic target. To identify compounds that are structurally
novel and diverse compared to previously reported ATP-competitive GSK-3beta
inhibitors, we performed virtual screening by implementing a mixed
ligand/structure-based approach, which included pharmacophore modeling, diversity
analysis, and ensemble docking. The sensitivities of different docking protocols
to induced-fit effects were explored. An enrichment study was employed to verify
the robustness of ensemble docking, using 13 X-ray structures of GSK-3beta,
compared to individual docking in terms of retrieving active compounds from a
decoy dataset. A total of 24 structurally diverse compounds obtained from the
virtual screening underwent biological validation. The bioassay results showed
that 15 out of the 24 hit compounds are indeed GSK-3beta inhibitors, and among
them, one compound exhibiting sub-micromolar inhibitory activity is a reasonable
starting point for further optimization.
PMID- 27486081
TI - Quantitative Structure-Activity Relationship Analysis and a Combined Ligand
Based/Structure-Based Virtual Screening Study for Glycogen Synthase Kinase-3.
AB - Glycogen synthase kinase-3 (GSK-3) is a multifunctional serine/threonine protein
kinase which regulates a wide range of cellular processes, involving various
signalling pathways. GSK-3beta has emerged as an important therapeutic target for
diabetes and Alzheimer's disease. To identify structurally novel GSK-3beta
inhibitors, we performed virtual screening by implementing a combined ligand
based/structure-based approach, which included quantitative structure-activity
relationship (QSAR) analysis and docking prediction. To integrate and analyze
complex data sets from multiple experimental sources, we drafted and validated a
hierarchical QSAR method, which adopts a two-level structure to take data
heterogeneity into account. A collection of 728 GSK-3 inhibitors with diverse
structural scaffolds was obtained from published papers that used different
experimental assay protocols. Support vector machines and random forests were
implemented with wrapper-based feature selection algorithms to construct
predictive learning models. The best models for each single group of compounds
were then used to build the final hierarchical QSAR model, with an overall R(2)
of 0.752 for the 141 compounds in the test set. The compounds obtained from the
virtual screening experiment were tested for GSK-3beta inhibition. The bioassay
results confirmed that 2 hit compounds are indeed GSK-3beta inhibitors exhibiting
sub-micromolar inhibitory activity, and therefore validated our combined ligand
based/structure-based approach as effective for virtual screening experiments.
PMID- 27486083
TI - Effects of salinity on short-term waterborne zinc uptake, accumulation and sub
lethal toxicity in the green shore crab (Carcinus maenas).
AB - Waterborne zinc (Zn) is known to cause toxicity to freshwater animals primarily
by disrupting calcium (Ca) homeostasis during acute exposure, but its effects in
marine and estuarine animals are not well characterized. The present study
investigated the effects of salinity on short-term Zn accumulation and sub-lethal
toxicity in the euryhaline green shore crab, Carcinus maenas. The kinetic and
pharmacological properties of short-term branchial Zn uptake were also examined.
Green crabs (n=10) were exposed to control (no added Zn) and 50MUM (3.25mgL(-1))
of waterborne Zn (~25% of 96h LC50 in 100 seawater) for 96h at 3 different
salinity regimes (100%, 60% and 20% seawater). Exposure to waterborne Zn
increased tissue-specific Zn accumulation across different salinities. However,
the maximum accumulation occurred in 20% seawater and no difference was recorded
between 60% and 100% seawater. Gills appeared to be the primary site of Zn
accumulation, since the accumulation was significantly higher in the gills
relative to the hepatopancreas, haemolymph and muscle. Waterborne Zn exposure
induced a slight increase in haemolymph osmolality and chloride levels
irrespective of salinity. In contrast, Zn exposure elicited marked increases in
both haemolymph and gill Ca levels, and these changes were more pronounced in 20%
seawater relative to that in 60% or 100% seawater. An in vitro gill perfusion
technique was used to examine the characteristics of short-term (1-4h) branchial
Zn uptake over an exposure concentration range of 3-12MUM (200-800MUgL(-1)). The
rate of short-term branchial Zn uptake did not change significantly after 2h, and
no difference was recorded in the rate of uptake between the anterior
(respiratory) and posterior (ion transporting) gills. The in vitro branchial Zn
uptake occurred in a concentration-dependent manner across different salinities.
However, the rate of uptake was consistently higher in 20% seawater relative to
60% or 100% seawater - similar to the trend observed with tissue Zn accumulation
during in vivo exposure. The short-term branchial Zn uptake was found to be
inhibited by lanthanum (a blocker of voltage-independent Ca channels), suggesting
that branchial Zn uptake occurs via the Ca transporting pathways, at least in
part. Overall, our findings indicate that acute exposure to waterborne Zn leads
to the disruption of Zn and Ca homeostasis in green crab, and these effects are
exacerbated at the lower salinity.
PMID- 27486082
TI - Single-cell analyses of X Chromosome inactivation dynamics and pluripotency
during differentiation.
AB - Pluripotency, differentiation, and X Chromosome inactivation (XCI) are key
aspects of embryonic development. However, the underlying relationship and
mechanisms among these processes remain unclear. Here, we systematically
dissected these features along developmental progression using mouse embryonic
stem cells (mESCs) and single-cell RNA sequencing with allelic resolution. We
found that mESCs grown in a ground state 2i condition displayed transcriptomic
profiles diffused from preimplantation mouse embryonic cells, whereas EpiStem
cells closely resembled the post-implantation epiblast. Sex-related gene
expression varied greatly across distinct developmental states. We also
identified novel markers that were highly enriched in each developmental state.
Moreover, we revealed that several novel pathways, including PluriNetWork and
Focal Adhesion, were responsible for the delayed progression of female EpiStem
cells. Importantly, we "digitalized" XCI progression using allelic expression of
active and inactive X Chromosomes and surprisingly found that XCI states
exhibited profound variability in each developmental state, including the 2i
condition. XCI progression was not tightly synchronized with loss of pluripotency
and increase of differentiation at the single-cell level, although these
processes were globally correlated. In addition, highly expressed genes,
including core pluripotency factors, were in general biallelically expressed.
Taken together, our study sheds light on the dynamics of XCI progression and the
asynchronicity between pluripotency, differentiation, and XCI.
PMID- 27486085
TI - Amorphous Li2 O2 : Chemical Synthesis and Electrochemical Properties.
AB - When aprotic Li-O2 batteries discharge, the product phase formed in the cathode
often contains two different morphologies, that is, crystalline and amorphous Li2
O2 . The morphology of Li2 O2 impacts strongly on the electrochemical performance
of Li-O2 cells in terms of energy efficiency and rate capability. Crystalline Li2
O2 is readily available and its properties have been studied in depth for Li-O2
batteries. However, little is known about the amorphous Li2 O2 because of its
rarity in high purity. Herein, amorphous Li2 O2 has been synthesized by a rapid
reaction of tetramethylammonium superoxide and LiClO4 in solution, and its
amorphous nature has been confirmed by a range of techniques. Compared with its
crystalline siblings, amorphous Li2 O2 demonstrates enhanced charge-transport
properties and increased electro-oxidation kinetics, manifesting itself a
desirable discharge phase for high-performance Li-O2 batteries.
PMID- 27486084
TI - Smoking and Posttraumatic Stress Disorder Symptomatology in Orofacial Pain.
AB - To explore the impact of interactions between smoking and symptoms of
posttraumatic stress disorder (PTSD) on pain intensity, psychological distress,
and pain-related functioning in patients with orofacial pain, a retrospective
review was conducted of data obtained during evaluations of 610 new patients with
a temporomandibular disorder who also reported a history of a traumatic event.
Pain-related outcomes included measures of pain intensity, psychological
distress, and pain-related functioning. Main effects of smoking status and PTSD
symptom severity on pain-related outcomes were evaluated with linear regression
analyses. Further analyses tested interactions between smoking status and PTSD
symptom severity on pain-related outcomes. PTSD symptom severity and smoking
predicted worse pain-related outcomes. Interaction analyses between PTSD symptom
severity and smoking status revealed that smoking attenuated the impact of PTSD
symptom severity on affective distress, although this effect was not found at
high levels of PTSD symptom severity. No other significant interactions were
found, but the present results identifying smoking as an ineffective coping
mechanism and the likely role of inaccurate outcome expectancies support the
importance of smoking cessation efforts in patients with orofacial pain. Smoking
is a maladaptive mechanism for coping with pain that carries significant health-
and pain-related risks while failing to fulfill smokers' expectations of affect
regulation, particularly among persons with orofacial pain who also have high
levels of PTSD symptom severity. Addressing smoking cessation is a critical
component of comprehensive treatment. Further research is needed to develop more
effective ways to help patients with pain and/or PTSD to replace smoking with
more effective coping strategies.
PMID- 27486086
TI - In-line phase-contrast breast tomosynthesis: a phantom feasibility study at a
synchrotron radiation facility.
AB - The major objective is to adopt, apply and test developed in-house algorithms for
volumetric breast reconstructions from projection images, obtained in in-line
phase-contrast mode. Four angular sets, each consisting of 17 projection images
obtained from four physical phantoms, were acquired at beamline ID17, European
Synchroton Radiation Facility, Grenoble, France. The tomosynthesis arc was +/-32
degrees . The physical phantoms differed in complexity of texture and introduced
features of interest. Three of the used phantoms were in-house developed, and
made of epoxy resin, polymethyl-methacrylate and paraffin wax, while the fourth
phantom was the CIRS BR3D. The projection images had a pixel size of 47 um * 47
um. Tomosynthesis images were reconstructed with standard shift-and-add (SAA) and
filtered backprojection (FBP) algorithms. It was found that the edge enhancement
observed in planar x-ray images is preserved in tomosynthesis images from both
phantoms with homogeneous and highly heterogeneous backgrounds. In case of BR3D,
it was found that features not visible in the planar case were well outlined in
the tomosynthesis slices. In addition, the edge enhancement index calculated for
features of interest was found to be much higher in tomosynthesis images
reconstructed with FBP than in planar images and tomosynthesis images
reconstructed with SAA. The comparison between images reconstructed by the two
reconstruction algorithms shows an advantage for the FBP method in terms of
better edge enhancement. Phase-contrast breast tomosynthesis realized in in-line
mode benefits the detection of suspicious areas in mammography images by adding
the edge enhancement effect to the reconstructed slices.
PMID- 27486087
TI - Factoring in the missing link.
PMID- 27486088
TI - Re-Evaluation of the Psychometric Properties of the Maternal-Fetal Attachment
Scale in a Hungarian Sample.
AB - OBJECTIVE: To explore the factor structure of the Maternal-Fetal Attachment Scale
(MFAS) and investigate its psychosocial and demographic correlates in a Hungarian
sample. DESIGN: Cross-sectional survey. SETTING: Sonography clinic in a
metropolitan area. PARTICIPANTS: One hundred fourteen women over the age of 18
years in the second or third trimesters of pregnancy. METHODS: Participants
completed the Hungarian version of the MFAS and provided information on
demographic, socioeconomic, and pregnancy-related factors. RESULTS: The internal
consistency of the MFAS total scale was acceptable (Cronbach's alpha = .87).
However, the reliability of the five subscales was low (alpha coefficients
between .57 and .74), and the original five-factor model was not supported by the
factor analyses. Married mothers had higher scores on the MFAS than participants
who were unmarried, and uncertainty about the sex of the fetus was associated
with lower attachment scores. Furthermore, gestational age showed a positive
correlation with MFAS scores. No significant association was found between the
total score on the MFAS and such factors as age, income, or education of the
parents; whether the pregnancy was planned; method of conception; number of
children born previously; prior perinatal losses; and circumstances of the
mother's own birth. CONCLUSION: Our study showed that marital status, uncertainty
about the sex of the fetus, and gestational age were associated with maternal
fetal attachment; however, more detailed analysis was not possible because of the
instability of the subscales of the instrument. Further research is warranted on
the underlying factors related to maternal-fetal attachment.
PMID- 27486089
TI - Case Report of Sepsis in Neonates Fed Expressed Mother's Milk.
AB - Mother's milk is the recommended food for premature infants cared for in the
NICU. In the cases presented in this article, mothers pumped their milk into food
grade aseptic plastic containers. Milk was refrigerated before use. In Case 1, an
infant developed Pseudomonas aeruginosa sepsis. In Case 2, an infant developed
methicillin-resistant Staphylococcus aureus. Both cases were attributed to
contaminated mother's milk. Proper cleaning and sterilization of pump parts is
essential to prevent milk contamination.
PMID- 27486091
TI - Academics should leave research credentials behind when they move, Stern report
says.
PMID- 27486090
TI - Fructose sensitizes Jurkat cells oxidative stress-induced apoptosis via caspase
dependent and caspase-independent mechanisms.
AB - Whether fructose (FRU), as the sole energy source, confers a metabolic advantage
on cancer cells against noxious stimuli is unknown. The aim of this study was to
evaluate the effects of low (11 mM), moderate (25 mM), and high (55 mM) FRU
concentrations alone or in combination with rotenone (ROT) or doxorubicin (DOX)
in Jurkat cells, an acute lymphoblastic leukemia cell model. Glucose (GLU) was
used as a control. Using different cell analysis techniques, we demonstrated that
FRU was predominantly metabolized via oxidative phosphorylation (~95%) (i.e.,
lactate production was reduced >120-fold), resulting in endogenous oxidative
stress-induced conditions. The cells were characterized by generation of O2*-
(43%)/ H2 O2 (40%) and activation of NF-kappaB (~95-fold increase, fi), c-Jun-N
terminal kinase (JNK), p53 (40-fi), and c-Jun (9-fi). In addition, we observed a
loss of DeltaPsim (10%), activation of caspase-3 (50-fi) and apoptosis-inducing
factor (AIF, 2-fi), and condensation and fragmentation of the nuclei [20% by
acridine orange/ethidium bromide/Hoechst (AO/EB/H) staining, 15% by flow
cytometry] compared to those of GLU 11 at 24 h. Although DOX killed Jurkat cells
independent of sugar content in the culture medium, leukemic cells in low, but
not high, FRU were extremely sensitive to ROT. Taken together, our findings
suggest that Jurkat cells are more susceptible to cell death if forced to shift
from GLU metabolism (i.e., aerobic glycolysis) to FRU metabolism (i.e., oxidative
phosphorylation) after treatment with mitochondria-targeting molecules. These
observations may help elucidate the cell death mechanism of leukemic cells
cultured in FRU.
PMID- 27486092
TI - Role of muscular eNOS in skeletal arteries: Endothelium-independent hypoxic
vasoconstriction of the femoral artery is impaired in eNOS-deficient mice.
AB - We previously reported that hypoxia augments alpha-adrenergic contraction
(hypoxic vasoconstriction, HVC) of skeletal arteries in rats. The underlying
mechanism may involve hypoxic inhibition of endothelial nitric oxide synthase
(eNOS) expressed in skeletal arterial myocytes (16). To further explore the novel
role of muscular eNOS in the skeletal artery, we compared HVC in femoral arteries
(FAs) from eNOS knockout (KO) mice with that from wild-type (WT) and heterozygous
(HZ) mice. Immunohistochemical assays revealed that, in addition to endothelia,
eNOS is also expressed in the medial layer of FAs, albeit at a much lower level.
However, the medial eNOS signal was not evident in HZ FAs, despite strong
expression in the endothelium; similar observations were made in WT carotid
arteries (CAs). The amplitude of contraction induced by 1 MUM phenylephrine (PhE)
was greater in HZ than in WT FAs. Hypoxia (3% Po2) significantly augmented PhE
induced contraction in WT FAs but not in HZ or KO FAs. No HVC was observed in PhE
pretreated WT CAs. The NOS inhibitor nitro-l-arginine methyl ester (0.1 mM) also
augmented PhE contraction in endothelium-denuded WT FAs but not in WT CAs.
Inhibitors specific to neuronal NOS and inducible NOS did not augment PhE-induced
contraction of WT FAs. NADPH oxidase 4 (NOX4) inhibitor (GKT137831, 5 MUM), but
not NOX2 inhibitor (apocynin, 100 MUM), suppressed HVC. Consistent with the role
of reactive oxygen species (ROS), HVC was also inhibited by pretreatment with
tiron or polyethylene glycol-catalase. Taken together, these data suggest that
the eNOS expressed in smooth muscle cells in FAs attenuates alpha-adrenergic
vasoconstriction; this suppression is alleviated under hypoxia, which potentiates
vasoconstriction in a NOX4/ROS-dependent mechanism.
PMID- 27486095
TI - Erratum.
PMID- 27486093
TI - Control of human energy expenditure by cytochrome c oxidase subunit IV-2.
AB - Resting metabolic rate (RMR) in humans shows pronounced individual variations,
but the underlying molecular mechanism remains elusive. Cytochrome c oxidase
(COX) plays a key role in control of metabolic rate, and recent studies of the
subunit 4 isoform 2 (COX IV-2) indicate involvement in the cellular response to
hypoxia and oxidative stress. We evaluated whether the COX subunit IV isoform
composition may explain the pronounced individual variations in resting metabolic
rate (RMR). RMR was determined in healthy humans by indirect calorimetry and
correlated to levels of COX IV-2 and COX IV-1 in vastus lateralis. Overexpression
and knock down of the COX IV isoforms were performed in primary myotubes followed
by evaluation of the cell respiration and production of reactive oxygen species.
Here we show that COX IV-2 protein is constitutively expressed in human skeletal
muscle and strongly correlated to RMR. Primary human myotubes overexpressing COX
IV-2 displayed markedly (>60%) lower respiration, reduced (>50%) cellular H2O2
production, higher resistance toward both oxidative stress, and severe hypoxia
compared with control cells. These results suggest an important role of isoform
COX IV-2 in the control of energy expenditure, hypoxic tolerance, and
mitochondrial ROS homeostasis in humans.
PMID- 27486094
TI - Intensification with pegylated interferon during treatment with tenofovir in HIV
hepatitis B virus co-infected patients.
AB - In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV)
mono-infection, intensification of nucleos(t)ide analogue treatment with
pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates.
Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)
containing antiretroviral therapy on seroclearance in HBeAg-positive patients co
infected with the human immunodeficiency virus (HIV) and HBV. In this prospective
matched cohort study, 46 patients with 1-year PegIFN intensification during TDF
containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls
undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based
on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification
(qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated
using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg
seroclearance was modelled using proportional hazards regression. At baseline,
previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg
and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10 IU/mL, respectively (P>.5
between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During
intensification, faster average declines of qHBeAg (-0.066 vs -0.027
PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10 IU/mL/month, P=.09)
were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After
intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7
and P=.9, respectively). Overall, no differences were observed in HBeAg
seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person.years, P=.5) or HBsAg
seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person.years, P=.7). In
conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not
lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of
antigen levels while on PegIFN.
PMID- 27486096
TI - Accelerated Stability Studies on Dried Extracts of Centella asiatica Through
Chemical, HPLC, HPTLC, and Biological Activity Analyses.
AB - Regulatory guidelines recommend systematic stability studies on a herbal product
to establish its shelf life. In the present study, commercial extracts (Types I
and II) and freshly prepared extract (Type III) of Centella asiatica were
subjected to accelerated stability testing for 6 months. Control and stability
samples were evaluated for organoleptics, pH, moisture, total phenolic content
(TPC), asiatic acid, kaempherol, and high-performance thin layer chromatography
fingerprints, and for antioxidant and acetylcholinesterase inhibitory activities.
Markers and TPC and both the activities of each extract decreased in stability
samples with respect to control. These losses were maximum in Type I extract and
minimum in Type III extract. Higher stability of Type III extract than others
might be attributed to the additional phytoconstituents and/or preservatives in
it. Pearson correlation analysis of the results suggested that TPC, asiatic acid,
and kaempferol can be taken as chemical markers to assess chemical and
therapeutic shelf lives of herbal products containing Centella asiatica.
PMID- 27486098
TI - NHS England to appeal against ruling that it can fund PrEP to prevent HIV.
PMID- 27486099
TI - Dozens of Turkish doctors are among those detained after coup.
PMID- 27486100
TI - Assessing the effects of 35 European-derived BMI-associated SNPs in Mexican
children.
AB - OBJECTIVE: The prevalence of obesity in Mexico has increased at an alarming rate
in both adults and children. This study was undertaken to test in Mexican
children the effects of single nucleotide polymorphisms (SNP) that have been
associated with body mass index (BMI) and obesity in Europeans. METHODS: School
age children (N = 1,559, 5-17 years) were recruited in Mexico City. Thirty-five
SNPs with established effects on BMI and obesity were genotyped and analyzed
individually and as a combined gene score (GS). RESULTS: SNPs in FAIM2
(rs7138803), GPRC5BB (rs12444979), MTIF3 (rs4771122), TFAP2B (rs987237), TMEM18
(rs7561317), and the GS were significantly associated with BMI. The GS explained
0.9% of the variance of BMI. Also, SNPs in LRRN6C (rs10968576) and MC4R
(rs17782313) were significantly associated with overweight and obesity
categories, respectively. Importantly, the effect allele frequency of 26/35 SNPs
(74.3%) differed significantly between Mexican children and European adults. No
significant gene * environment or gene * gene interactions were detected after
Bonferroni adjustment. CONCLUSIONS: Several SNPs first associated with
BMI/obesity in European adults replicated well in Mexican children, and
investigating differences in the distribution of effect alleles across ethnic
populations may shed light on genetic susceptibilities of different populations
to obesity.
PMID- 27486097
TI - Germline variation in inflammation-related pathways and risk of Barrett's
oesophagus and oesophageal adenocarcinoma.
AB - OBJECTIVE: Oesophageal adenocarcinoma (OA) incidence has risen sharply in Western
countries over recent decades. Local and systemic inflammation is considered an
important contributor to OA pathogenesis. Established risk factors for OA and its
precursor, Barrett's oesophagus (BE), include symptomatic reflux, obesity and
smoking. The role of inherited genetic susceptibility remains an area of active
investigation. Here, we explore whether germline variation related to
inflammatory processes influences susceptibility to BE/OA. DESIGN: We used data
from a genomewide association study of 2515 OA cases, 3295 BE cases and 3207
controls. Our analysis included 7863 single-nucleotide polymorphisms (SNPs) in
449 genes assigned to five pathways: cyclooxygenase (COX), cytokine signalling,
oxidative stress, human leucocyte antigen and nuclear factor-kappaB. A principal
components-based analytic framework was employed to evaluate pathway-level and
gene-level associations with disease risk. RESULTS: We identified a significant
signal for the COX pathway in relation to BE risk (p=0.0059, false discovery rate
q=0.03), and in gene-level analyses found an association with microsomal
glutathione-S-transferase 1 (MGST1); (p=0.0005, q=0.005). Assessment of 36 MGST1
SNPs identified 14 variants associated with elevated BE risk (q<0.05). Four of
these were subsequently confirmed (p<5.5*10-5) in a meta-analysis encompassing an
independent set of 1851 BE cases and 3496 controls, and are known strong
expression quantitative trait loci for MGST1. Three such variants were associated
with similar elevations in OA risk. CONCLUSIONS: This study provides the most
comprehensive evaluation of inflammation-related germline variation in relation
to risk of BE/OA and suggests that variants in MGST1 influence disease
susceptibility.
PMID- 27486101
TI - Velocity dependence of vestibular information for postural control on tilting
surfaces.
AB - Vestibular information is known to be important for postural stability on tilting
surfaces, but the relative importance of vestibular information across a wide
range of surface tilt velocities is less clear. We compared how tilt velocity
influences postural orientation and stability in nine subjects with bilateral
vestibular loss and nine age-matched, control subjects. Subjects stood on a force
platform that tilted 6 deg, toes-up at eight velocities (0.25 to 32 deg/s), with
and without vision. Results showed that visual information effectively
compensated for lack of vestibular information at all tilt velocities. However,
with eyes closed, subjects with vestibular loss were most unstable within a
critical tilt velocity range of 2 to 8 deg/s. Subjects with vestibular deficiency
lost their balance in more than 90% of trials during the 4 deg/s condition, but
never fell during slower tilts (0.25-1 deg/s) and fell only very rarely during
faster tilts (16-32 deg/s). At the critical velocity range in which falls
occurred, the body center of mass stayed aligned with respect to the surface,
onset of ankle dorsiflexion was delayed, and there was delayed or absent
gastrocnemius inhibition, suggesting that subjects were attempting to actively
align their upper bodies with respect to the moving surface instead of to
gravity. Vestibular information may be critical for stability at velocities of 2
to 8 deg/s because postural sway above 2 deg/s may be too fast to elicit
stabilizing responses through the graviceptive somatosensory system, and postural
sway below 8 deg/s may be too slow for somatosensory-triggered responses or
passive stabilization from trunk inertia.
PMID- 27486102
TI - Air-Track: a real-world floating environment for active sensing in head-fixed
mice.
AB - Natural behavior occurs in multiple sensory and motor modalities and in
particular is dependent on sensory feedback that constantly adjusts behavior. To
investigate the underlying neuronal correlates of natural behavior, it is useful
to have access to state-of-the-art recording equipment (e.g., 2-photon imaging,
patch recordings, etc.) that frequently requires head fixation. This limitation
has been addressed with various approaches such as virtual reality/air ball or
treadmill systems. However, achieving multimodal realistic behavior in these
systems can be challenging. These systems are often also complex and expensive to
implement. Here we present "Air-Track," an easy-to-build head-fixed behavioral
environment that requires only minimal computational processing. The Air-Track is
a lightweight physical maze floating on an air table that has all the properties
of the "real" world, including multiple sensory modalities tightly coupled to
motor actions. To test this system, we trained mice in Go/No-Go and two
alternative forced choice tasks in a plus maze. Mice chose lanes and
discriminated apertures or textures by moving the Air-Track back and forth and
rotating it around themselves. Mice rapidly adapted to moving the track and used
visual, auditory, and tactile cues to guide them in performing the tasks. A
custom-controlled camera system monitored animal location and generated data that
could be used to calculate reaction times in the visual and somatosensory
discrimination tasks. We conclude that the Air-Track system is ideal for
eliciting natural behavior in concert with virtually any system for monitoring or
manipulating brain activity.
PMID- 27486103
TI - Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens.
AB - The human nucleus accumbens is thought to play an important role in guiding
future action selection via an evaluation of current action outcomes. Here we
provide electrophysiological evidence for a more direct, i.e., online, role
during action preparation. We recorded local field potentials from the nucleus
accumbens in patients with epilepsy undergoing surgery for deep brain
stimulation. We found a consistent decrease in the power of alpha/beta
oscillations (10-30 Hz) before and around the time of movements. This
perimovement alpha/beta desynchronization was observed in seven of eight patients
and was present both before instructed movements in a serial reaction time task
as well as before self-paced, deliberate choices in a decision making task. A
similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has
been directly related to movement preparation and execution. Our results support
the idea of a direct role of the human nucleus accumbens in action preparation
and execution.
PMID- 27486104
TI - Firing characteristics of deep dorsal horn neurons after acute spinal transection
during administration of agonists for 5-HT1B/1D and NMDA receptors.
AB - Spinal cord injury (SCI) results in a loss of serotonin (5-HT) to the spinal cord
and a loss of inhibition to deep dorsal horn (DDH) neurons, which produces an
exaggerated excitatory drive to motoneurons. The mechanism of this excitatory
drive could involve the DDH neurons triggering long excitatory postsynaptic
potentials in motoneurons, which may ultimately drive muscle spasms. Modifying
the activity of DDH neurons with drugs such as NMDA or the 5-HT1B/1D receptor
agonist zolmitriptan could have a large effect on motoneuron activity and,
therefore, on muscle spasms. In this study, we characterize the firing properties
of DDH neurons after acute spinal transection in adult mice during administration
of zolmitriptan and NMDA, using the in vitro sacral cord preparation and
extracellular electrophysiology. DDH neurons can be categorized into three major
types with distinct evoked and spontaneous firing characteristics: burst
(bursting), simple (single spiking), and tonic (spontaneously tonic firing)
neurons. The burst neurons likely contribute to muscle spasm mechanisms because
of their bursting behavior. Only the burst neurons show significant changes in
their firing characteristics during zolmitriptan and NMDA administration.
Zolmitriptan suppresses the burst neurons by reducing their evoked spikes, burst
duration, and spontaneous firing rate. Conversely, NMDA facilitates them by
enhancing their burst duration and spontaneous firing rate. These results suggest
that zolmitriptan may exert its antispastic effect on the burst neurons via
activation of 5-HT1B/1D receptors, whereas activation of NMDA receptors may
facilitate the burst neurons in contributing to muscle spasm mechanisms following
SCI.
PMID- 27486105
TI - Live interaction distinctively shapes social gaze dynamics in rhesus macaques.
AB - The dynamic interaction of gaze between individuals is a hallmark of social
cognition. However, very few studies have examined social gaze dynamics after
mutual eye contact during real-time interactions. We used a highly quantifiable
paradigm to assess social gaze dynamics between pairs of monkeys and modeled
these dynamics using an exponential decay function to investigate sustained
attention after mutual eye contact. When monkeys were interacting with real
partners compared with static images and movies of the same monkeys, we found a
significant increase in the proportion of fixations to the eyes and a smaller
dispersion of fixations around the eyes, indicating enhanced focal attention to
the eye region. Notably, dominance and familiarity between the interacting pairs
induced separable components of gaze dynamics that were unique to live
interactions. Gaze dynamics of dominant monkeys after mutual eye contact were
associated with a greater number of fixations to the eyes, whereas those of
familiar pairs were associated with a faster rate of decrease in this eye
directed attention. Our findings endorse the notion that certain key aspects of
social cognition are only captured during interactive social contexts and
dependent on the elapsed time relative to socially meaningful events.
PMID- 27486106
TI - Initial information prior to movement onset influences kinematics of upward arm
pointing movements.
AB - To elaborate a motor plan and perform online control in the gravity field, the
brain relies on priors and multisensory integration of information. In
particular, afferent and efferent inputs related to the initial state are thought
to convey sensorimotor information to plan the upcoming action. Yet it is still
unclear to what extent these cues impact motor planning. Here we examined the
role of initial information on the planning and execution of arm movements.
Participants performed upward arm movements around the shoulder at three speeds
and in two arm conditions. In the first condition, the arm was outstretched
horizontally and required a significant muscular command to compensate for the
gravitational shoulder torque before movement onset. In contrast, in the second
condition the arm was passively maintained in the same position with a cushioned
support and did not require any muscle contraction before movement execution. We
quantified differences in motor performance by comparing shoulder velocity
profiles. Previous studies showed that asymmetric velocity profiles reflect an
optimal integration of the effects of gravity on upward movements. Consistent
with this, we found decreased acceleration durations in both arm conditions.
However, early differences in kinematic asymmetries and EMG patterns between the
two conditions signaled a change of the motor plan. This different behavior
carried on through trials when the arm was at rest before movement onset and may
reveal a distinct motor strategy chosen in the context of uncertainty.
Altogether, we suggest that the information available online must be complemented
by accurate initial information.
PMID- 27486107
TI - The antiepileptic and ictogenic effects of optogenetic neurostimulation of PV
expressing interneurons.
AB - Parvalbumin (PV)-expressing interneurons exert powerful inhibitory effects on the
normal cortical network; thus optogenetic activation of PV interneurons may also
possess antiepileptic properties. To investigate this possibility we expressed
channelrhodopsin 2 in PV interneurons by locally injecting the Cre-dependent
viral vector AAV2/1-EF1a-DIO-ChETA-EYFP into the S1 barrel cortex of PV-Cre mice.
Approximately 3-4 wk later recurrent electrographic seizures were evoked by local
application of the chemoconvulsant 4-aminopyridine (4-AP); the ECoG and unit
activity were monitored with extracellular silicone electrodes; and PV
interneurons were activated optogenetically during the ictal and interictal
phases. Five- to ten-second optogenetic activation of PV interneurons applied
during electrographic seizures (ictal phase) terminated 33.7% of electrographic
seizures compared with only 6% during sham stimulation, and the average
electrographic seizure duration shortened by 38.7 +/- 34.2% compared with sham
stimulation. In contrast, interictal optogenetic activation of PV interneurons
showed powerful and robust ictogenic effects. Approximately 60% of interictal
optogenetic stimuli resulted in electrographic seizure initiation. Single-unit
recordings revealed that presumptive PV-expressing interneurons markedly
increased their firing during optogenetic stimulation, while many presumptive
excitatory pyramidal neurons showed a biphasic response, with initial suppression
of firing during the optogenetic pulse followed by a synchronized rebound
increase in firing at the end of the laser pulse. Our findings indicated that
ictal activation of PV-expressing interneurons possesses antiepileptic properties
probably due to suppression of firing in pyramidal neurons during the laser
pulse. However, in addition interictal activation of PV-expressing interneurons
possesses powerful ictogenic properties, probably due to synchronized
postinhibition rebound firing of pyramidal neurons.
PMID- 27486108
TI - Growth restriction induced by chronic prenatal hypoxia affects breathing rhythm
and its pontine catecholaminergic modulation.
AB - Impaired transplacental supply of oxygen leads to intrauterine growth
restriction, one of the most important causes of perinatal mortality and
respiratory morbidity. Breathing rhythm depends on the central respiratory
network modulated by catecholamines. We investigated the impact of growth
restriction, using prenatal hypoxia, on respiratory frequency, on central
respiratory-like rhythm, and on its catecholaminergic modulation after birth. At
birth, respiratory frequency was increased and confirmed in en bloc medullary
preparations, where the frequency of the fourth cervical (C4) ventral root
discharge was increased, and in slice preparations containing the pre-Botzinger
complex with an increased inspiratory rhythm. The inhibition of C4 burst
discharge observed in pontomedullary preparations was stronger in the growth
restricted group. These results cannot be directly linked by the tyrosine
hydroxylase activity increase of A1/C1 and A2/C2 cell groups in the medulla since
blockade of alpha1- and alpha2-adrenergic receptors did not abolish the
difference between both groups. However, in pontomedullary preparations, the
stronger inhibition of C4 burst discharge is probably supported by an increased
inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons
displaying increased tyrosine hydroxylase activity, because blockade of alpha2
adrenergic receptors abolished the difference between the two groups. Taken
together, these results indicate that growth restriction leads to a perturbation
of the breathing frequency, which finds, at least in part, its origin in the
modification of catecholaminergic modulation of the central breathing network.
PMID- 27486109
TI - Savings for visuomotor adaptation require prior history of error, not prior
repetition of successful actions.
AB - When we move, perturbations to our body or the environment can elicit
discrepancies between predicted and actual outcomes. We readily adapt movements
to compensate for such discrepancies, and the retention of this learning is
evident as savings, or faster readaptation to a previously encountered
perturbation. The mechanistic processes contributing to savings, or even the
necessary conditions for savings, are not fully understood. One theory suggests
that savings requires increased sensitivity to previously experienced errors:
when perturbations evoke a sequence of correlated errors, we increase our
sensitivity to the errors experienced, which subsequently improves error
correction (Herzfeld et al. 2014). An alternative theory suggests that a memory
of actions is necessary for savings: when an action becomes associated with
successful target acquisition through repetition, that action is more rapidly
retrieved at subsequent learning (Huang et al. 2011). In the present study, to
better understand the necessary conditions for savings, we tested how savings is
affected by prior experience of similar errors and prior repetition of the action
required to eliminate errors using a factorial design. Prior experience of errors
induced by a visuomotor rotation in the savings block was either prevented at
initial learning by gradually removing an oppositely signed perturbation or
enforced by abruptly removing the perturbation. Prior repetition of the action
required to eliminate errors in the savings block was either deprived or enforced
by manipulating target location in preceding trials. The data suggest that prior
experience of errors is both necessary and sufficient for savings, whereas prior
repetition of a successful action is neither necessary nor sufficient for
savings.
PMID- 27486110
TI - Subretinal electrical stimulation reveals intact network activity in the blind
mouse retina.
AB - Retinal degeneration (rd) leads to progressive photoreceptor cell death,
resulting in vision loss. Stimulation of the inner-retinal neurons by
neuroprosthetic implants is one of the clinically approved vision-restoration
strategies, providing basic visual percepts to blind patients. However, little is
understood as to what degree the degenerating retinal circuitry and the resulting
aberrant hyperactivity may prevent the stimulation of physiological electrical
activity. Therefore, we electrically stimulated ex vivo retinas from wild-type
(wt; C57BL/6J) and blind (rd10 and rd1) mice using an implantable subretinal
microchip and simultaneously recorded and analyzed the retinal ganglion cell
(RGC) output with a flexible microelectrode array. We found that subretinal
anodal stimulation of the rd10 retina and wt retina evoked similar spatiotemporal
RGC-spiking patterns. In both retinas, electrically stimulated ON and a small
percentage of OFF RGC responses were detected. The spatial selectivity of the
retinal network to electrical stimuli reveals an intact underlying network with a
median receptive-field center of 350 MUm in both retinas. An antagonistic
surround is activated by stimulation with large electrode fields. However, in
rd10 and to a higher percentage, in rd1 retinas, rhythmic and spatially
unconfined RGC patterns were evoked by anodal or by cathodal electrical stimuli.
Our findings demonstrate that the surviving retinal circuitry in photoreceptor
degenerated retinas is preserved in a way allowing for the stimulation of
temporally diverse and spatially confined RGC activity. Future vision restoration
strategies can build on these results but need to avoid evoking the easily
inducible rhythmic activity in some retinal circuits.
PMID- 27486111
TI - Spike synchrony generated by modulatory common input through NMDA-type synapses.
AB - Common excitatory input to neurons increases their firing rates and the strength
of the spike correlation (synchrony) between them. Little is known, however,
about the synchronizing effects of modulatory common input. Here, we show that
modulatory common input with the slow synaptic kinetics of N-methyl-d-aspartate
(NMDA) receptors enhances firing rates and also produces synchrony. Tight
synchrony (correlations on the order of milliseconds) always increases with
modulatory strength. Unexpectedly, the relationship between strength of
modulation and strength of loose synchrony (tens of milliseconds) is not
monotonic: The strongest loose synchrony is obtained for intermediate modulatory
amplitudes. This finding explains recent neurophysiological results showing that
in cortical areas V1 and V2, presumed modulatory top-down input due to contour
grouping increases (loose and tight) synchrony but that additional modulatory
input due to top-down attention does not change tight synchrony and actually
decreases loose synchrony. These neurophysiological findings are understood from
our model of integrate-and-fire neurons under the assumption that contour
grouping as well as attention lead to additive modulatory common input through
NMDA-type synapses. In contrast, circuits with common projections through model
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors did not
exhibit the paradoxical decrease of synchrony with increased input. Our results
suggest that NMDA receptors play a critical role in top-down response modulation
in the visual cortex.
PMID- 27486113
TI - Editorial Commentary: Sliding Down the Cascade of Care for Chronic Hepatitis B
Virus Infection.
PMID- 27486112
TI - No Evidence of Reactivation of Hepatitis B Virus Among Patients Treated With
Ledipasvir-Sofosbuvir for Hepatitis C Virus Infection.
AB - Postmarketing cases of hepatitis B virus (HBV) reactivation during hepatitis C
treatment have been reported. We analyzed serum samples from patients in a
clinical trial of ledipasvir-sofosbuvir in Taiwan and Korea. Of the 173 patients
enrolled, 103 (60%) had been previously infected with HBV. None showed evidence
of HBV reactivation.
PMID- 27486114
TI - Case-Control Study of Vaccine Effectiveness in Preventing Laboratory-Confirmed
Influenza Hospitalizations in Older Adults, United States, 2010-2011.
AB - BACKGROUND: Older adults are at increased risk of influenza-associated
complications, including hospitalization, but influenza vaccine effectiveness
(VE) data are limited for this population. We conducted a case-control study to
estimate VE to prevent laboratory-confirmed influenza hospitalizations among
adults aged >=50 years in 11 US Emerging Infections Program hospitalization
surveillance sites. METHODS: Cases were influenza infections (confirmed by
reverse-transcription polymerase chain reaction) in adults aged >=50 years
hospitalized during the 2010-2011 influenza season, identified through Emerging
Infections Program surveillance. Community controls, identified through home
telephone lists, were matched by age group (+/-5 years), county, and month of
hospitalization for case patients. Vaccination status was determined by self
report (with location and date) or medical records. Conditional logistic
regression models were used to calculate adjusted VE (aVE) estimates (100 * [1 -
adjusted odds ratio]), adjusting for sex, race, socioeconomic factors, smoking,
chronic medical conditions, recent hospitalization for a respiratory condition,
and functional status. RESULTS: Among case patients, 205 of 368 (55%) were
vaccinated, compared with 489 of 773 controls (63%). Case patients were more
likely to be of nonwhite race and more likely to have >=2 chronic health
conditions, a recent hospitalization for a respiratory condition, an income <$35
000, and a lower functional status score (P < .01 for all). The aVE was 56.8%
(95% confidence interval, 34.1%-71.7%) and was similar across age groups,
including adults >=75 years (aVE, 57.3%; 15.9%-78.4%). CONCLUSIONS: During 2010
2011, influenza vaccination was associated with a significant reduction in the
risk of laboratory-confirmed influenza hospitalization among adults aged >=50
years, regardless of age group.
PMID- 27486115
TI - Infrequent Clinical Assessment of Chronic Hepatitis B Patients in United States
General Healthcare Settings.
AB - Among 2338 chronic hepatitis B patients followed during 2006-2013 in the Chronic
Hepatitis Cohort Study, 78% had >=1 alanine aminotransferase and 37% had >=1
hepatitis B virus DNA level assessed annually. Among cirrhotic patients, 46%
never had hepatic imaging. Patients in this cohort were insufficiently monitored
for disease activity and hepatocellular carcinoma.
PMID- 27486116
TI - Spread of Carbapenem-Resistant Enterobacteriaceae Among Illinois Healthcare
Facilities: The Role of Patient Sharing.
AB - BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) spread regionally
throughout healthcare facilities through patient transfer and cause difficult-to
treat infections. We developed a state-wide patient-sharing matrix and applied
social network analyses to determine whether greater connectedness (centrality)
to other healthcare facilities and greater patient sharing with long-term acute
care hospitals (LTACHs) predicted higher facility CRE rates. METHODS: We combined
CRE case information from the Illinois extensively drug-resistant organism
registry with measures of centrality calculated from a state-wide hospital
discharge dataset to predict facility-level CRE rates, adjusting for hospital
size and geographic characteristics. RESULTS: Higher CRE rates were observed
among facilities with greater patient sharing, as measured by degree centrality.
Each additional hospital connection (unit of degree) conferred a 6% increase in
CRE rate in rural facilities (relative risk [RR] = 1.056; 95% confidence interval
[CI], 1.030-1.082) and a 3% increase among Chicagoland and non-Chicago urban
facilities (RR = 1.027; 95% CI, 1.002-1.052 and RR = 1.025; 95% CI, 1.002-1.048,
respectively). Sharing 4 or more patients with LTACHs was associated with higher
CRE rates, but this association may have been due to chance (RR = 2.08; 95% CI,
.85-5.08; P = .11). CONCLUSIONS: Hospitals with greater connectedness to other
hospitals in a statewide patient-sharing network had higher CRE burden.
Centrality had a greater effect on CRE rates in rural counties, which do not have
LTACHs. Social network analysis likely identifies hospitals at higher risk of CRE
exposure, enabling focused clinical and public health interventions.
PMID- 27486118
TI - Seo YB et al (Clin Infect Dis 2016; 62:755-60).
PMID- 27486117
TI - Karanika S et al (Clin Infect Dis 2016; 63:310-18).
PMID- 27486119
TI - Editorial Commentary: Network Models, Patient Transfers, and Infection Control.
PMID- 27486120
TI - Zoophthora radicans (Entomophthorales), a fungal pathogen of Bagrada hilaris and
Bactericera cockerelli (Hemiptera: Pentatomidae and Triozidae): Prevalence,
pathogenicity, and interplay of environmental influence, morphology, and sequence
data on fungal identification.
AB - The exotic bagrada bug or painted bug, Bagrada hilaris, and the native
potato/tomato psyllid, Bactericera (=Paratrioza) cockerelli, are key pests of
horticulture in western North America. In 2014-2015, adult and juvenile B.
hilaris and B. cockerelli killed by fungi in the genus Zoophthora were detected
near Saltillo, northeastern Mexico. We report the field prevalence and
observations of Zoophthora on these hosts. The morphology and growth
characteristics of field-collected specimens and pure in vitro cultures, as well
as molecular markers (ITS1 and ITS4) were analyzed to identify these Zoophthora
populations. Although there were morphological spore differences detected among
field collections from both insect hosts, the fungi causing these mycoses can be
identified as the same species (Zoophthora radicans), according to morphometric
data from in vitro cultures (where differences observed in field material were
attenuated) and sequence data (96-99% identity for ITS1 and 4). These results
underscore the plasticity of field collections and in vitro cultures, and the
relevance of comprehensive morphological and molecular analysis from cultures
under standard conditions. Dose-response bioassays were conducted with one Z.
radicans strain against bagrada bug nymphs. Exposure to conidial showers from
cultures induced 30-90% mortality. This is the first report of a natural enemy of
bagrada bug in Mexico, and the first published report of entomophthoralean fungi
naturally attacking bagrada bugs and potato psyllids. Z. radicans should be
further investigated as a tool in the biological control of hemipterans.
PMID- 27486121
TI - Revisiting protein structure, function, and evolution in the genomic era.
AB - The expansion of genomic data, three-dimensional structures of proteins, and
computing power continues to improve our understanding of the evolution of
protein structure and function relationships. As of June 2016, publically
available databases contain more than 60 million unique protein sequences that
group into 16,295 protein families that adopt ~1400 different three-dimensional
folds. This data supports the exploration of evolutionary relationships on
protein structure and function to answer a basic question - how do changes in
gene sequence lead to alterations in protein structure and to the tailoring of
biological and chemical function? This mini-review aims to provide a primer on
the basics of protein structure, how evolution of sequence leads to diversity in
protein structure and function, how these changes occur, and the role of domains
in protein evolution. Understanding how to use the vast amount of sequence and
structural information may also aid in assessing if changes in protein sequence
and/or structure are relevant for safety assessments of new commercial
biotechnology products.
PMID- 27486122
TI - Supplementation of vitamin B12 or folic acid on hemoglobin concentration in
children 6-36 months of age: A randomized placebo controlled trial.
AB - BACKGROUND & AIMS: The main objective of this report is to measure to what extent
folate or vitamin B12 given daily for 6 months to young North Indian Children
improves hemoglobin (Hb) concentration. METHODS: In a randomized placebo
controlled trial in low-to-middle income neighborhoods in New Delhi, India,
children were randomized into four groups in a 1:1:1:1 ratio and supplemented
daily for 6 months with 2 RDAs of vitamin B12, folic acid, both, or placebo. All
children with anemia at baseline were given iron supplementation daily for 2
months. We measured the plasma concentrations of soluble transferrin receptor
(sTfR), folate, vitamin B12, total homocysteine (tHcy) and Hb in 262 children.
RESULTS: Mean Hb concentration decreased in all four study groups during the six
months of follow up and supplementation of either or both of the vitamins did not
improve the Hb concentration. Iron supplements for the initial 2 mo had limited
effect on anemia at 6 mo as almost 90% were still anemic at study end.
CONCLUSION: Supplementation of folic acid and/or vitamin B12 for 6 months does
not improve Hb concentration in young children. Our findings do not argue for
widespread vitamin B12 or folic acid supplementation to combat anemia. Our
results also call for alternative strategies to improve iron status and treat
iron deficiency anemia. CLINICAL TRIAL REGISTRY: NCT00717730 at
www.clinicaltrials.gov, CTRI No.: CTRI/2010/091/001090 at www.ctri.nic.in.
PMID- 27486123
TI - Feasibility of nephrinuria as a screening tool for the risk of pre-eclampsia:
prospective observational study.
AB - OBJECTIVES: To investigate the possibility of nephrinuria as a screening tool for
the risk of pre-eclampsia (PE). DESIGN: Prospective observational study. SETTING:
A single university hospital. Changes in urinary nephrin:creatinine ratio (NCR,
ng/mg) and protein:creatinine ratio (PCR, mg/mg) in pregnancy were determined.
Significant proteinuria in pregnancy (SPIP) was defined as PCR>0.27. PE was
diagnosed in women with both SPIP and hypertension. PARTICIPANTS: 89 pregnant
women in whom neither hypertension nor SPIP was present at enrolment, providing
31, 125 and 93 random urine samples during first, second and third trimesters,
respectively. RESULTS: PE developed in 14 of the 89 women. NCR increased with
increasing PCR in 14 women with PE (correlation coefficient, 0.862; p<0.0001). In
contrast, NCR did not change significantly despite significant increases in PCR
in 75 women with normotensive pregnancies defined as neither SPIP nor
hypertension, indicating that there was little increase in nephrinuria over the
physiological range of proteinuria in pregnancy. Relative risk of later
development of PE among asymptomatic second and third trimester women with NCR
(ng/mg) >122 (95th centile value for 75 women with normotensive pregnancies) was
5.93 (95% CI 2.59 to 13.6; 60% (6/10) vs 10% (8/79)) and 13.5 (95% CI 3.31 to
55.0; 75% (6/8) vs 5.5% (2/36)), respectively, compared with women with NCR<=122
at that time. CONCLUSIONS: Nephrinuria was unlikely to increase in normal
pregnancy. A certain NCR cut-off may efficiently differentiate women at higher
risk of PE.
PMID- 27486125
TI - Lipid changes during basal insulin peglispro, insulin glargine, or NPH treatment
in six IMAGINE trials.
AB - Basal insulin peglispro (BIL) is a novel basal insulin with hepato-preferential
action resulting from reduced peripheral effects. This report provides an
integrated summary of lipid changes at 26 weeks with BIL and comparator insulins
(glargine, NPH) from phase III studies in type 1 diabetes (T1D), insulin-naive
patients with type 2 diabetes (T2D), patients with T2D on basal insulin only and
patients with T2D on basal-bolus therapy. BIL treatment had little effect on HDL
cholesterol and LDL cholesterol in all patients. The effect of both BIL and
glargine treatment on triglycerides (TG) depended on whether patients had been
previously treated with insulin. When BIL replaced conventional insulin glargine
or NPH treatments, increases in TG levels were observed. When BIL or comparator
insulins were given for 26 weeks to insulin-naive patients with T2D, TG levels
were unchanged from baseline with BIL but decreased with either glargine or NPH.
The decreased peripheral action of BIL may reduce suppression of lipolysis in
peripheral adipose tissue resulting in increased free fatty acid delivery to the
liver and, hence, increased hepatic TG synthesis and secretion.
PMID- 27486126
TI - Women's Empowerment as a Protective Factor Against Intimate Partner Violence in
Bangladesh: A Qualitative Exploration of the Process and Limitations of Its
Influence.
AB - Literature on the relationship between intimate partner violence (IPV) against
women and women's empowerment is contradictory. Findings from a recent survey in
rural Bangladesh suggest that empowerment is becoming protective even though IPV
rates remain high. We construct qualitative case studies exploring factors and
social processes underlying relationships between empowerment and IPV in four
villages. Empowerment may be protective against IPV in the aggregate, but this
relationship can be subverted at the micro level. Interventions are needed to
reinforce the potential of empowerment to reduce IPV and counteract factors such
as geographic isolation and limited employment opportunities that inhibit
empowerment.
PMID- 27486124
TI - Visually Impaired OLder people's Exercise programme for falls prevenTion
(VIOLET): a feasibility study protocol.
AB - INTRODUCTION: In the UK, 1 in 5 people aged 75 and over live with sight loss.
Visually impaired older people (VIOP) have an above average incidence of falls
and 1.3-1.9 times more likely to experience hip fractures, than the general
population. Older people with eye diseases are ~3 times more likely than those
with good vision, to limit activities due to fear of falling. This feasibility
study aims to adapt the group-based Falls Management Exercise (FaME) programme to
the needs of VIOP and carry out an external pilot trial to inform the design of a
future definitive randomised controlled trial. METHODS AND DESIGN: A UK based 2
centre mixed methods, randomised, feasibility study will be conducted over 28
months. Stakeholder panels, including VIOP, will make recommendations for
adaptations to an existing exercise programme (FaME), to meet the needs of VIOP,
promoting uptake and adherence, while retaining required effective components of
the exercise programme. 80 VIOP aged 60 and over, living at home, ambulant with
or without a walking aid, will be recruited in Newcastle (n=40) and Glasgow
(n=40) through National Health Service (NHS) Trusts and third sector partners.
Participants randomised into the intervention arm will receive the adapted FaME
programme. Participants randomised into the control arm will continue with usual
activity. Outcomes are, recruitment rate, adherence and validated measures
including fear of falling and quality of life. Postintervention in-depth
qualitative interviews will be conducted with a purposive sample of VIOP (N=10).
Postural stability instructors will be interviewed, before trial-specific
training and following the intervention. ETHICS AND DISSEMINATION: Ethics
approval was secured through the National Research Ethics Service (NRES)
Committee North East, Newcastle and North Tyneside 2. Glasgow Caledonian
University was approved as a non-NHS site with local ethics approval. Findings
will be disseminated through peer-reviewed journals, national and international
conferences. TRIAL REGISTRATION NUMBER: ISRCTN16949845.
PMID- 27486127
TI - Differences in Mental Health and Sexual Outcomes Based on Type of Nonconsensual
Sexual Penetration.
AB - Little is known based on the stratification and localization of penetration type
of rape: oral, vaginal, and/or anal. The current study examined associations
between type of rape and mental and sexual health symptoms in 865 community
women. All penetration types were positively associated with negative mental and
sexual health symptoms. Oral and/or anal rape accounted for additional variance
in anxiety, depression, some trauma-related symptoms, and dysfunctional sexual
behavior than the association with vaginal rape alone. Findings suggest that
penetration type can be an important facet of a rape experience and may be useful
to assess in research and clinical settings.
PMID- 27486128
TI - Calling the Shots: How Family Courts Address the Firearms Ban in Protection
Orders.
AB - Access to firearms increases the risk of a batterer killing his partner.
Moreover, firearms may be more common in homes where intimate partner abuse has
occurred. The Violence Against Women Act of 1994 banned possession of firearms by
individuals subject to civil protection orders. Yet little research has focused
on how this ban is communicated to survivors and batterers. Drawing on systematic
observations of protection order hearings, the current study explores factors
related to judicial discussion of the ban in court. Implications for improving
protection orders and for increasing battered women's safety are discussed.
PMID- 27486129
TI - Comment on 'A new method to measure electron density and effective atomic number
using dual-energy CT images'.
PMID- 27486130
TI - Effect of race/ethnicity on risk of complete and partial molar pregnancy after
adjustment for age.
AB - OBJECTIVE: To quantify the effect of race/ethnicity on risk of complete and
partial molar pregnancy. METHODS: We conducted a cross-sectional study including
women who were followed for complete or partial mole and those who had a live
singleton birth in a teaching hospital in the northeastern United States between
2000 and 2013. We calculated race/ethnicity-specific risk of complete and partial
mole per 10,000 live births, and used logistic regression to estimate crude and
age-adjusted relative risks (RR) of complete and partial mole. RESULTS: We
identified 140 cases of complete mole, 115 cases of partial mole, and 105,942
live births. The risk of complete mole was 13 cases per 10,000 live births (95%
confidence interval [CI] 11-16) and that of partial mole was 11 cases per 10,000
live births (95% CI 9-13). After age-adjustment, Asians were more likely to
develop complete mole (RR 2.3 95% CI 1.4-3.8, p<0.001) but less likely to develop
partial mole (RR 0.2; 95% CI 0.04-0.7, p=0.02) than whites. Blacks were
significantly less likely than whites to develop partial mole (RR 0.4; 95% CI 0.2
0.8, p=0.01) but only marginally less likely to develop complete mole (RR 0.6;
95% CI 0.3-1.0, p=0.07). Hispanics were less likely than whites to develop
complete mole (RR 0.4; 95% CI 0.2-0.7, p=0.002) and partial mole (RR 0.4; 95% CI
0.2-0.9, p=0.02). CONCLUSION: Race/ethnicity is a significant risk factor for
both complete and partial molar pregnancy in the northeastern United States.
PMID- 27486131
TI - Impact of postoperative intensity-modulated radiation therapy (IMRT) on the rate
of bowel obstruction in gynecologic malignancy.
AB - OBJECTIVE: The purpose was to determine the potential impact of IMRT on the rate
of bowel obstruction (BO), in patients with gynecologic malignancies undergoing
postoperative pelvic RT. METHODS: We performed a retrospective review of all
patients with endometrial or cervical cancer who received postoperative pelvic RT
at our institution from 2000 to 2012. Patients who received definitive or
palliative RT, or those with BO due to disease progression, were excluded.
Standard two-sided statistical tests were used to evaluate for associated risk
factors. Kaplan-Meier, Log rank and Cox proportional hazards regression analysis
tests were performed for actuarial analysis. RESULTS: A total of 224 patients
were identified, 120 (54%) received postoperative pelvic IMRT and 104 (46%) 3
dimentional (3-D) RT. Median follow-up time was 67months. BO was grade 1
(asymptomatic) in 2/228 (0.9%), grade 2 (conservative management) in 4 (1.8%),
and grade 3>= in 4 (1.8%). Overall, the 5-year actuarial rate of BO was 4.8%. The
5-year rate of BO in the IMRT group was 0.9% compared to 9.3% for 3-D RT
(p=0.006). Patients with BMI>=30kg/m(2) were less likely to develop BO (2.6% vs.
8.3; p=0.03). On multivariate analysis, only IMRT retained its significance as an
independent predictor of less BO (p=0.022). CONCLUSIONS: The use of postoperative
IMRT for cervical and endometrial cancer was associated with significant
reduction in the rate of bowel obstruction. This difference maintained its
statistical significance on multivariate analysis. Such finding if confirmed by
others will help further solidify the benefit of IMRT in gynecologic cancers.
PMID- 27486132
TI - Boari flap ureteroneocystostomy in an oncological patient.
AB - OBJECTIVE: Demonstration of surgical steps of a Boari Flap ureteroneocystostomy
in an oncological context. METHODS: Clinical case of a 66-year-old woman
diagnosed with a left-pelvic recurrence of a high-grade serous ovarian carcinoma,
involving the left ureter. After transection of 5cm of ureteral length, up to the
level of the bifurcation of common iliac vessels, it was decided to perform a
Boari Flap for ureteral reimplantation. RESULTS: Through the tubularization of a
bladder flap, the extension of the ureter to the bladder is possible. After
mobilization and psoas fixation, the bladder is opened on its anterior surface,
in a rhomboid incision, and a full thickness bladder flap is extended cranially
and tubularized for anastomosis of the proximal ureteral segment. The ureter is
reimplanted after creation of an anti-reflux system with a submucosal tunnel
between the mucosa and the detrusor. To finish the procedure, the bladder is
closed in two layers with a running monofilament absorbable suture. CONCLUSIONS:
Boari Flap ureteroneocystostomy is an uncommon urinary reconstruction, useful to
correct distal ureteric defects caused by traumatic, oncological or iatrogenic
injuries [1]. The success rate of ureteral reimplantation can be higher than 85%
[2]. This technique is suitable for anastomosis of lumbar ureteral segments,
allowing the better correction of higher and more extensive defects than the
Psoas-Hitch technique. The flap length should compensate the ureteric defect and
enable a tension free anastomosis.
PMID- 27486133
TI - Emergency department imaging: are weather and calendar factors associated with
imaging volume?
AB - AIM: To identify weather and calendar factors that would enable prediction of
daily emergency department (ED) imaging volume to aid appropriate scheduling of
imaging resources for efficient ED function. MATERIALS AND METHODS: Daily ED
triage and imaging volumes for radiography, computed tomography (CT), and
ultrasound were obtained from hospital databases for the period between January
2011 and December 2013 at a large tertiary urban hospital with a Level II trauma
centre. These data were tabulated alongside daily weather conditions
(temperature, wind and precipitation), day of week, season, and holidays.
Multivariate analysis was performed. Pearson correlations were used to measure
the association between number of imaging studies performed and ED triage volume.
RESULTS: For every additional 50 triaged patients, the odds of having high
(imaging volume >=90th percentile) radiography, CT, and ultrasound volume
increased by 4.3 times (p<0.001), 1.5 times (p=0.02), and 1.4 times (p=0.02),
respectively. Tuesday was an independent predictor of high radiography volume
(odds ratio=2.8) and Monday was an independent predictor of high CT volume (odds
ratio=3.0). Weekday status was an independent factor increasing the odds of a
high US volume compared to Saturday (odds ratios ranging from 5.6-9.8). Weather
factors and other calendar variables were not independent predictors of high
imaging volume. Using Pearson correlations, ED triage volume correlated with
number of radiographs, CT, and ultrasound examinations with r=0.73, 0.37, and
0.41, respectively (p<0.0001). CONCLUSION: As ED triage volume was found to be
the only factor associated with imaging volume for all techniques, analysis of
predictors of ED triage volumes at a particular healthcare facility would be
useful to determine imaging needs. Although calendar and weather factors were
found to be minor or non-significant independent predictors of ED imaging
utilisation, these may be important in influencing the actual number of ED
triages.
PMID- 27486135
TI - The impact of intestinal resection on the immune function of short bowel syndrome
patients.
AB - Short bowel syndrome (SBS) is characterized by a massive intestinal loss after
surgery resection. Likewise, disturbances involving the intestine, which
represents a complex immune environment, may result in breakdown of homeostasis
and altered responses, thus leading to unpredictable clinical outcomes. However,
the consequences of bowel resection were poorly investigated until now.
Therefore, this study aimed to evaluate the immunological status of SBS-patients.
For this purpose, ten subjects and nine healthy controls were evaluated. Along
with some metabolic disturbances, the main results showed higher levels of the
inflammatory cytokine IL-6 in plasma among SBS-patients. However, there were no
differences in the frequency of CD3+, CD3+CD4+ or CD3+CD8+ T lymphocytes. An
augmented frequency in CD4+ and CD8+ cells producing IFN-gamma was also observed
in peripheral blood mononuclear cells (PBMC), together with elevated percentage
of CD4+ cells producing IL-10. No differences were observed in the frequency of
total CD4+CD25-, CD4+CD25+ lymphocytes nor in the expression of FoxP3 or GITR.
Nevertheless, SBS-patients showed higher frequency of the regulatory T cell
population CD4+CD25+CD39+ cells in PBMC. In conclusion, these data pointed to SBS
as an important disturbance that compromises not only the intestinal environment
but also negatively influences systemic immune components.
PMID- 27486134
TI - Amyloid-beta Precursor Protein Modulates the Sorting of Testican-1 and
Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from
Patients with Alzheimer Disease.
AB - The mechanisms leading to amyloid-beta (Abeta) accumulation in sporadic Alzheimer
disease (AD) are unknown but both increased production or impaired clearance
likely contribute to aggregation. To understand the potential roles of the
extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we
used samples from AD patients and controls and an in vitro approach. Protein
expression analysis showed increased levels of Testican-1 in frontal and temporal
cortex of AD patients; histological analysis showed that Testican-1 accumulates
and co-aggregates with Abeta plaques in the frontal, temporal and entorhinal
cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1
in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human
wild type or mutant Abeta precursor protein (APP) were transfected with Testican
1. The co-expression of both proteins modified the sorting of Testican-1 into the
endocytic pathway leading to its transient accumulation in Golgi, which seemed to
affect APP processing, as indicated by reduced Abeta40 and Abeta42 levels in APP
mutant cells. In conclusion, patient data reflect a clearance impairment that may
favor Abeta accumulation in AD brains and our in vitro model supports the notion
that the interaction between APP and Testican-1 may be a key step in the
production and aggregation of Abeta species.
PMID- 27486136
TI - Paradoxical Response to Enzyme Replacement Therapy of Fabry Disease
Cardiomyopathy.
PMID- 27486137
TI - Understanding the Personality and Behavioral Mechanisms Defining Hypersexuality
in Men Who Have Sex With Men.
AB - INTRODUCTION: Hypersexuality has been conceptualized as sexual addiction,
compulsivity, and impulsivity, among others, in the absence of strong empirical
data in support of any specific conceptualization. AIM: To investigate
personality factors and behavioral mechanisms that are relevant to hypersexuality
in men who have sex with men. METHODS: A sample of 242 men who have sex with men
was recruited from various sites in a moderate-size mid-western city.
Participants were assigned to a hypersexuality group or a control group using an
interview similar to the Structured Clinical Interview for the Diagnostic and
Statistical Manual for Mental Disorders, Fourth Edition. Self-report inventories
were administered that measured the broad personality constructs of positive
emotionality, negative emotionality, and constraint and more narrow constructs
related to sexual behavioral control, behavioral activation, behavioral
inhibition, sexual excitation, sexual inhibition, impulsivity, attention
deficit/hyperactivity disorder, and sexual behavior. MAIN OUTCOME MEASURES:
Hierarchical logistic regression was used to determine the relation between these
personality and behavioral variables and group membership. RESULTS: A
hierarchical logistic regression controlling for age showed a significant
positive relation between hypersexuality and negative emotionality and a negative
relation with constraint. None of the behavioral mechanism variables entered this
equation. However, a hierarchical multiple regression analysis predicting sexual
behavioral control indicated that lack of such control was positively related to
sexual excitation and sexual inhibition owing to the threat of performance
failure and negatively related to sexual inhibition owing to the threat of
performance consequences and general behavioral inhibition CONCLUSION:
Hypersexuality was found to be related to two broad personality factors that are
characterized by emotional reactivity, risk taking, and impulsivity. The
associated lack of sexual behavior control is influenced by sexual excitatory and
inhibitory mechanisms, but not by general behavioral activation and inhibitory
mechanisms.
PMID- 27486139
TI - Hyperplastic stomatitis and esophagitis in a tortoise (Testudo graeca) associated
with an adenovirus infection.
AB - A 2-year-old female, spur-thighed tortoise (Testudo graeca) was presented with
poor body condition (1/5) and weakness. Fecal analysis revealed large numbers of
oxyurid-like eggs, and radiographs were compatible with gastrointestinal
obstruction. Despite supportive medical treatment, the animal died. At gross
examination, an intestinal obstruction was confirmed. Histopathology revealed
severe hyperplastic esophagitis and stomatitis with marked epithelial cytomegaly
and enormous basophilic intranuclear inclusion bodies. Electron microscopy
examination revealed a large number of 60-80 nm, nonenveloped, icosahedral
virions arranged in crystalline arrays within nuclear inclusions of esophageal
epithelial cells, morphologically compatible with adenovirus-like particles. PCR
for virus identification was performed with DNA extracted from formalin-fixed,
paraffin-embedded tissues. A nested, consensus pan-adenovirus PCR and sequencing
analysis showed a novel adenovirus. According to phylogenetic calculations, it
clustered to genus Atadenovirus in contrast with all other chelonian adenoviruses
described to date. The present report details the pathologic findings associated
with an adenovirus infection restricted to the upper digestive tract.
PMID- 27486140
TI - Incidence, Determinants, and Outcomes of Coronary Perforation During Percutaneous
Coronary Intervention in the United Kingdom Between 2006 and 2013: An Analysis of
527 121 Cases From the British Cardiovascular Intervention Society Database.
AB - BACKGROUND: As coronary perforation (CP) is a rare but serious complication of
percutaneous coronary intervention (PCI) the current evidence base is limited to
small series. Using a national PCI database, the incidence, predictors, and
outcomes of CP as a complication of PCI were defined. METHODS AND RESULTS: Data
were prospectively collected and retrospectively analyzed from the British
Cardiovascular Intervention Society data set on all PCI procedures performed in
England and Wales between 2006 and 2013. Multivariate logistic regressions and
propensity scores were used to identify predictors of CP and its association with
outcomes. In total, 1762 CPs were recorded from 527 121 PCI procedures (incidence
of 0.33%). Patients with CP were more often women or older, with a greater burden
of comorbidity and underwent more complex PCI procedures. Factors predictive of
CP included age per year (odds ratio [OR], 1.03; 95% confidence intervals, 1.02
1.03; P<0.001), previous coronary artery bypass graft (OR, 1.44; 95% confidence
intervals, 1.17-1.77; P<0.001), left main (OR, 1.54; 95% confidence intervals,
1.21-1.96; P<0.001), use of rotational atherectomy (OR, 2.37; 95% confidence
intervals, 1.80-3.11; P<0.001), and chronic total occlusions intervention (OR,
3.96; 95% confidence intervals, 3.28-4.78; P<0.001). Adjusted odds of adverse
outcomes were higher in patients with CP for all major adverse coronary events,
including stroke, bleeding, and mortality. Emergency surgery was required in 3%
of cases. Predictors of mortality in patients with CP included age, diabetes
mellitus, previous myocardial infarction, renal disease, ventilatory support, use
of circulatory support, glycoprotein inhibitor use, and stent type. CONCLUSIONS:
Using a national PCI database for the first time, the incidence, predictors, and
outcomes of CP were defined. Although CP as a complication of PCI occurred
rarely, it was strongly associated with poor outcomes.
PMID- 27486138
TI - Mendelian Randomization as an Approach to Assess Causality Using Observational
Data.
AB - Mendelian randomization refers to an analytic approach to assess the causality of
an observed association between a modifiable exposure or risk factor and a
clinically relevant outcome. It presents a valuable tool, especially when
randomized controlled trials to examine causality are not feasible and
observational studies provide biased associations because of confounding or
reverse causality. These issues are addressed by using genetic variants as
instrumental variables for the tested exposure: the alleles of this exposure
associated genetic variant are randomly allocated and not subject to reverse
causation. This, together with the wide availability of published genetic
associations to screen for suitable genetic instrumental variables make Mendelian
randomization a time- and cost-efficient approach and contribute to its
increasing popularity for assessing and screening for potentially causal
associations. An observed association between the genetic instrumental variable
and the outcome supports the hypothesis that the exposure in question is causally
related to the outcome. This review provides an overview of the Mendelian
randomization method, addresses assumptions and implications, and includes
illustrative examples. We also discuss special issues in nephrology, such as
inverse risk factor associations in advanced disease, and outline opportunities
to design Mendelian randomization studies around kidney function and disease.
PMID- 27486141
TI - Promising effects of oxytocin on social and food-related behaviour in young
children with Prader-Willi syndrome: a randomized, double-blind, controlled
crossover trial.
AB - BACKGROUND: Prader-Willi syndrome (PWS) is known for hyperphagia with impaired
satiety and a specific behavioural phenotype with stubbornness, temper tantrums,
manipulative and controlling behaviour and obsessive-compulsive features. PWS is
associated with hypothalamic and oxytocinergic dysfunction. In humans without
PWS, intranasal oxytocin administration had positive effects on social and eating
behaviour, and weight balance. OBJECTIVE AND HYPOTHESES: To evaluate the effects
of intranasal oxytocin compared to placebo administration on social behaviour and
hyperphagia in children with PWS. DESIGN: Randomized, double-blind, placebo
controlled, crossover study in a PWS Reference Center in the Netherlands. METHOD:
Crossover intervention with twice daily intranasal oxytocin (dose range 24-48
IU/day) and placebo administration, both during 4 weeks, in 25 children with PWS
(aged 6 to 14 years). RESULTS: In the total group, no significant effects of
oxytocin on social behaviour or hyperphagia were found, but in the 17 children
younger than 11 years, parents reported significantly less anger (P = 0.001),
sadness (P = 0.005), conflicts (P = 0.010) and food-related behaviour (P =
0.011), and improvement of social behaviour (P = 0.018) during oxytocin treatment
compared with placebo. In the eight children older than 11 years, the items
happiness (P = 0.039), anger (P = 0.042) and sadness (P = 0.042) were negatively
influenced by oxytocin treatment compared to placebo. There were no side effects
or adverse events. CONCLUSIONS: This randomized, double-blind, placebo-controlled
study suggests that intranasal oxytocin administration has beneficial effects on
social behaviour and food-related behaviour in children with PWS younger than 11
years of age, but not in those older than 11 years of age.
PMID- 27486142
TI - Improvements in ECG accuracy for diagnosis of left ventricular hypertrophy in
obesity.
AB - OBJECTIVES: The electrocardiogram (ECG) is the most commonly used tool to screen
for left ventricular hypertrophy (LVH), and yet current diagnostic criteria are
insensitive in modern increasingly overweight society. We propose a simple
adjustment to improve diagnostic accuracy in different body weights and improve
the sensitivity of this universally available technique. METHODS: Overall, 1295
participants were included-821 with a wide range of body mass index (BMI 17.1
53.3 kg/m(2)) initially underwent cardiac magnetic resonance evaluation of
anatomical left ventricular (LV) axis, LV mass and 12-lead surface ECG in order
to generate an adjustment factor applied to the Sokolow-Lyon criteria. This
factor was then validated in a second cohort (n=520, BMI 15.9-63.2 kg/m(2)).
RESULTS: When matched for LV mass, the combination of leftward anatomical axis
deviation and increased BMI resulted in a reduction of the Sokolow-Lyon index, by
4 mm in overweight and 8 mm in obesity. After adjusting for this in the initial
cohort, the sensitivity of the Sokolow-Lyon index increased (overweight: 12.8% to
30.8%, obese: 3.1% to 27.2%) approaching that seen in normal weight (37.8%).
Similar results were achieved in the validation cohort (specificity increased in
overweight: 8.3% to 39.1%, obese: 9.4% to 25.0%) again approaching normal weight
(39.0%). Importantly, specificity remained excellent (>93.1%). CONCLUSIONS:
Adjusting the Sokolow-Lyon index for BMI (overweight +4 mm, obesity +8 mm)
improves the diagnostic accuracy for detecting LVH. As the ECG, worldwide,
remains the most widely used screening tool for LVH, implementing these findings
should translate into significant clinical benefit.
PMID- 27486143
TI - An algorithm for rule-in and rule-out of acute myocardial infarction using a
novel troponin I assay.
AB - OBJECTIVE: To derive and validate a hybrid algorithm for rule-out and rule-in of
acute myocardial infarction based on measurements at presentation and after 2
hours with a novel cardiac troponin I (cTnI) assay. METHODS: The algorithm was
derived and validated in two cohorts (605 and 592 patients) from multicentre
studies enrolling chest pain patients presenting to the emergency department (ED)
with onset of last episode within 12 hours. The index diagnosis and
cardiovascular events up to 30 days were adjudicated by independent reviewers.
RESULTS: In the validation cohort, 32.6% of the patients were ruled out on ED
presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22%
could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the
patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI
97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were
ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%)
and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained
undetermined after 2 hours. No patient in the rule-out group died during the 30
day follow-up in the two cohorts. CONCLUSIONS: This novel two-step algorithm
based on cTnI measurements enabled just over a third of the patients with acute
chest pain to be ruled in or ruled out already at presentation and an additional
third after 2 hours. This strategy maximises the speed of rule-out and rule-in
while maintaining a high NPV and PPV, respectively.
PMID- 27486145
TI - Medical students writing on death, dying and palliative care: a qualitative
analysis of reflective essays.
AB - BACKGROUND: Medical students and doctors are becoming better prepared to care for
patients with palliative care needs and support patients at the end of life. This
preparation needs to start at medical school. OBJECTIVE: To assess how medical
students learn about death, dying and palliative care during a clinical placement
using reflective essays and to provide insights to improve medical education
about end-of-life care and/or palliative care. METHODS: Qualitative study in
which all reflective essays written by third-year medical students in 1 year from
a UK medical school were searched electronically for those that included 'death',
'dying' and 'palliative care'. The anonymised data were managed using QSR NVivo
10 software, and a systematic analysis was conducted in three distinct phases:
(1) open coding; (2) axial coding and (3) selective coding. Ethical approval was
received. RESULTS: 54 essays met the inclusion criteria from 241 essays screened
for the terms 'death', 'dying' or 'palliative'; 22 students gave consent for
participation and their 24 essays were included. Saturation of themes was
reached. Three overarching themes were identified: emotions, empathy and
experiential and reflective learning. Students emphasised trying to develop a
balance between showing empathy and their emotional state. Students learnt a lot
from clinical encounters and watching doctors manage difficult situations, as
well as from their refection during and after the experience. CONCLUSIONS:
Reflective essays give insights into the way students learn about death, dying
and palliative care and how it affects them personally as well as the preparation
that is needed to be better equipped to deal with these kinds of experiences.
Analysis of the essays enabled the proposal of new strategies to help make them
more effective learning tools and to optimise students' learning from a
palliative care attachment.
PMID- 27486146
TI - International palliative care research in the context of global development: a
systematic mapping review.
AB - CONTEXT: An increasing amount of health policy is formulated at global level. At
this global level, palliative care has attracted support primarily from normative
institutions (WHO), not funding agencies. To attract greater global attention
from policymakers, it has been argued that an international approach to research
is required. However, the extent to which an international approach is being
undertaken is unknown. OBJECTIVES: To systematically identify and thematically
synthesise all international palliative care research, defined as research
involving two or more countries, or focused on the global level. METHODS: Five
bibliographic databases (CINAHL, Cochrane Library, ASSIA, Web of Knowledge,
Psychinfo) were searched for journal articles relevant to international and
global palliative care and end-of-life care. Data were extracted using a piloted
extraction form and findings were synthesised. RESULTS: 184 studies were
included, published across 75 different academic journals. Research emanates from
and focuses on all world regions and there is increasing focus on the global
level. Thematically, there is a high focus on Evaluation (n=53) and views of
Stakeholders (n=38). The review revealed a predominantly observational research
approach and few interventional studies were identified. CONCLUSIONS:
International palliative care research is a relatively new, but growing field.
However, many gaps in the evidence base remain and palliative care research
continues to take place outside broader discourses of international development.
The relative absence of interventional research demonstrating the effectiveness
and cost-effectiveness of palliative care risks limiting the tools with which
advocates can engage with international policymakers on this topic.
PMID- 27486144
TI - Left ventricular hypertrophy by ECG versus cardiac MRI as a predictor for heart
failure.
AB - OBJECTIVE: To determine if there is a significant difference in the predictive
abilities of left ventricular hypertrophy (LVH) detected by ECG-LVH versus LVH
ascertained by cardiac MRI-LVH in a model similar to the Framingham Heart Failure
Risk Score (FHFRS). METHODS: This study included 4745 (mean age 61+/-10 years,
53.5% women, 61.7% non-whites) participants in the Multi-Ethnic Study of
Atherosclerosis. ECG-LVH was defined using Cornell voltage product while MRI-LVH
was derived from left ventricular mass. Cox proportional hazard regression was
used to examine the association between ECG-LVH and MRI-LVH with incident heart
failure (HF). Harrell's concordance C-index was used to estimate the predictive
ability of the model when either ECG-LVH or MRI-LVH was included as one of its
components. RESULTS: ECG-LVH was present in 291 (6.1%), while MRI-LVH was present
in 499 (10.5%) of the participants. Both ECG-LVH (HR 2.25, 95% CI 1.38 to 3.69)
and MRI-LVH (HR 3.80, 95% CI 1.56 to 5.63) were predictive of HF. The absolute
risk of developing HF was 8.81% for MRI-LVH versus 2.26% for absence of MRI-LVH
with a relative risk of 3.9. With ECG-LVH, the absolute risk of developing HF
6.87% compared with 2.69% for absence of ECG-LVH with a relative risk of 2.55.
The ability of the model to predict HF was better with MRI-LVH (C-index 0.871,
95% CI 0.842 to 0.899) than with ECG-LVH (C-index 0.860, 95% CI 0.833 to 0.888)
(p<0.0001). CONCLUSIONS: ECG-LVH and MRI-LVH are predictive of HF. Substituting
MRI-LVH for ECG-LVH improves the predictive ability of a model similar to the
FHFRS.
PMID- 27486147
TI - Rasip1-Mediated Rho GTPase Signaling Regulates Blood Vessel Tubulogenesis via
Nonmuscle Myosin II.
AB - RATIONALE: Vascular tubulogenesis is essential to cardiovascular development.
Within initial vascular cords of endothelial cells, apical membranes are
established and become cleared of cell-cell junctions, thereby allowing
continuous central lumens to open. Rasip1 (Ras-interacting protein 1) is required
for apical junction clearance, as well as for regulation of Rho GTPase (enzyme
that hydrolyzes GTP) activity. However, it remains unknown how activities of
different Rho GTPases are coordinated by Rasip1 to direct tubulogenesis.
OBJECTIVE: The aim of this study is to determine the mechanisms downstream of
Rasip1 that drive vascular tubulogenesis. METHODS AND RESULTS: Using conditional
mouse mutant models and pharmacological approaches, we dissect GTPase pathways
downstream of Rasip1. We show that clearance of endothelial cell apical junctions
during vascular tubulogenesis depends on Rasip1, as well as the GTPase Cdc42
(cell division control protein 42 homolog) and the kinase Pak4 (serine/threonine
protein kinase 4). Genetic deletion of Rasip1 or Cdc42, or inhibition of Pak4,
all blocks endothelial cell tubulogenesis. By contrast, inactivation of RhoA (Ras
homologue gene family member A) signaling leads to vessel overexpansion,
implicating actomyosin contractility in control of lumen diameter. Interestingly,
blocking activity of NMII (nonmuscle myosin II) either before, or after, lumen
morphogenesis results in dramatically different tubulogenesis phenotypes,
suggesting time-dependent roles. CONCLUSIONS: Rasip1 controls different pools of
GTPases, which in turn regulate different pools of NMII to coordinate junction
clearance (remodeling) and actomyosin contractility during vascular
tubulogenesis. Rasip1 promotes activity of Cdc42 to activate Pak4, which in turn
activates NMII, clearing apical junctions. Once lumens open, Rasip1 suppresses
actomyosin contractility via inhibition of RhoA by Arhgap29, allowing controlled
expansion of vessel lumens during embryonic growth. These findings elucidate the
stepwise processes regulated by Rasip1 through downstream Rho GTPases and NMII.
PMID- 27486148
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section
3. Pharmacological Treatments.
AB - BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT)
conducted a revision of the 2009 guidelines by updating the evidence and
recommendations. The scope of the 2016 guidelines remains the management of major
depressive disorder (MDD) in adults, with a target audience of psychiatrists and
other mental health professionals. METHODS: Using the question-answer format, we
conducted a systematic literature search focusing on systematic reviews and meta
analyses. Evidence was graded using CANMAT-defined criteria for level of
evidence. Recommendations for lines of treatment were based on the quality of
evidence and clinical expert consensus. "Pharmacological Treatments" is the third
of six sections of the 2016 guidelines. With little new information on older
medications, treatment recommendations focus on second-generation
antidepressants. RESULTS: Evidence-informed responses are given for 21 questions
under 4 broad categories: 1) principles of pharmacological management, including
individualized assessment of patient and medication factors for antidepressant
selection, regular and frequent monitoring, and assessing clinical and functional
outcomes with measurement-based care; 2) comparative aspects of antidepressant
medications based on efficacy, tolerability, and safety, including summaries of
newly approved drugs since 2009; 3) practical approaches to pharmacological
management, including drug-drug interactions and maintenance recommendations; and
4) managing inadequate response and treatment resistance, with a focus on
switching antidepressants, applying adjunctive treatments, and new and emerging
agents. CONCLUSIONS: Evidence-based pharmacological treatments are available for
first-line treatment of MDD and for management of inadequate response. However,
given the limitations of the evidence base, pharmacological management of MDD
still depends on tailoring treatments to the patient.
PMID- 27486149
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section
6. Special Populations: Youth, Women, and the Elderly.
AB - BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT)
conducted a revision of the 2009 guidelines by updating the evidence and
recommendations. The scope of the 2016 guidelines remains the management of major
depressive disorder (MDD) in adults, with a target audience of psychiatrists and
other mental health professionals. METHODS: Using the question-answer format, we
conducted a systematic literature search focusing on systematic reviews and meta
analyses. Evidence was graded using CANMAT-defined criteria for level of
evidence. Recommendations for lines of treatment were based on the quality of
evidence and clinical expert consensus. This section on "Special Populations" is
the sixth of six guidelines articles. RESULTS: Recent studies inform the
treatment of MDD in children and adolescents, pregnant and breastfeeding women,
women in perimenopause or menopause, and the elderly. Evidence for efficacy of
treatments in these populations is more limited than for the general adult
population, however, and risks of treatment in these groups are often poorly
studied and reported. CONCLUSIONS: Despite the limited evidence base, extant data
and clinical experience suggest that each of these special populations can
benefit from the systematic application of treatment guidelines for treatment of
MDD.
PMID- 27486152
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder:
Introduction and Methods.
PMID- 27486150
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section
2. Psychological Treatments.
AB - BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) has
revised its 2009 guidelines for the management of major depressive disorder (MDD)
in adults by updating the evidence and recommendations. The target audiences for
these 2016 guidelines are psychiatrists and other mental health professionals.
METHODS: Using the question-answer format, we conducted a systematic literature
search focusing on systematic reviews and meta-analyses. Evidence was graded
using CANMAT-defined criteria for level of evidence. Recommendations for lines of
treatment were based on the quality of evidence and clinical expert consensus.
"Psychological Treatments" is the second of six sections of the 2016 guidelines.
RESULTS: Evidence-informed responses were developed for 25 questions under 5
broad categories: 1) patient characteristics relevant to using psychological
interventions; 2) therapist and health system characteristics associated with
optimizing outcomes; 3) descriptions of major psychotherapies and their efficacy;
4) additional psychological interventions, such as peer interventions and
computer- and technology-delivered interventions; and 5) combining and/or
sequencing psychological and pharmacological interventions. CONCLUSIONS: First
line psychological treatment recommendations for acute MDD include cognitive
behavioural therapy (CBT), interpersonal therapy (IPT), and behavioural
activation (BA). Second-line recommendations include computer-based and telephone
delivered psychotherapy. Where feasible, combining psychological treatment (CBT
or IPT) with antidepressant treatment is recommended because combined treatment
is superior to either treatment alone. First-line psychological treatments for
maintenance include CBT and mindfulness-based cognitive therapy (MBCT). Patient
preference, in combination with evidence-based treatments and clinician/system
capacity, will yield the optimal treatment strategies for improving individual
outcomes in MDD.
PMID- 27486151
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section
1. Disease Burden and Principles of Care.
AB - BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT)
conducted a revision of the 2009 guidelines by updating the evidence and
recommendations. The scope of the 2016 guidelines remains the management of major
depressive disorder (MDD) in adults, with a target audience of psychiatrists and
other mental health professionals. METHODS: Using the question-answer format, we
conducted a systematic literature search focusing on systematic reviews and meta
analyses. Evidence was graded using CANMAT-defined criteria for level of
evidence. Recommendations for lines of treatment were based on the quality of
evidence and clinical expert consensus. This section is the first of six
guidelines articles. RESULTS: In Canada, the annual and lifetime prevalence of
MDD was 4.7% and 11.3%, respectively. MDD represents the second leading cause of
global disability, with high occupational and economic impact mainly attributable
to indirect costs. DSM-5 criteria for depressive disorders remain relatively
unchanged, but other clinical dimensions (sleep, cognition, physical symptoms)
may have implications for depression management. e-Mental health is increasingly
used to support clinical and self-management of MDD. In the 2-phase (acute and
maintenance) treatment model, specific goals address symptom remission,
functional recovery, improved quality of life, and prevention of recurrence.
CONCLUSIONS: The burden attributed to MDD remains high, whether from individual
distress, functional and relationship impairment, reduced quality of life, or
societal economic cost. Applying core principles of care, including comprehensive
assessment, therapeutic alliance, support of self-management, evidence-informed
treatment, and measurement-based care, will optimize clinical, quality of life,
and functional outcomes in MDD.
PMID- 27486153
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section
5. Complementary and Alternative Medicine Treatments.
AB - BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT)
conducted a revision of the 2009 guidelines by updating the evidence and
recommendations. The scope of the 2016 guidelines remains the management of major
depressive disorder (MDD) in adults, with a target audience of psychiatrists and
other mental health professionals. METHODS: Using the question-answer format, we
conducted a systematic literature search focusing on systematic reviews and meta
analyses. Evidence was graded using CANMAT-defined criteria for level of
evidence. Recommendations for lines of treatment were based on the quality of
evidence and clinical expert consensus. "Complementary and Alternative Medicine
Treatments" is the fifth of six sections of the 2016 guidelines. RESULTS:
Evidence-informed responses were developed for 12 questions for 2 broad
categories of complementary and alternative medicine (CAM) interventions: 1)
physical and meditative treatments (light therapy, sleep deprivation, exercise,
yoga, and acupuncture) and 2) natural health products (St. John's wort, omega-3
fatty acids; S-adenosyl-L-methionine [SAM-e], dehydroepiandrosterone, folate,
Crocus sativus, and others). Recommendations were based on available data on
efficacy, tolerability, and safety. CONCLUSIONS: For MDD of mild to moderate
severity, exercise, light therapy, St. John's wort, omega-3 fatty acids, SAM-e,
and yoga are recommended as first- or second-line treatments. Adjunctive exercise
and adjunctive St. John's wort are second-line recommendations for moderate to
severe MDD. Other physical treatments and natural health products have less
evidence but may be considered as third-line treatments. CAM treatments are
generally well tolerated. Caveats include methodological limitations of studies
and paucity of data on long-term outcomes and drug interactions.
PMID- 27486155
TI - Association between naturally occurring antiamyloid beta autoantibodies and
medial temporal lobe atrophy in Alzheimer's disease.
PMID- 27486156
TI - Assessment of different pre-treatment methods for the removal of limonene in
citrus waste and their effect on methane potential and methane production rate.
AB - The objective of this study was to assess the limonene removal efficiency of
three pre-treatment methods when applied to citrus waste and to evaluate their
effects on the biochemical methane potential and the methane production rate
using batch anaerobic tests. The methods tested were based on removal (biological
pretreatment by fungi) or recovery (steam distillation and ethanol extraction) of
limonene. All the treatments decreased the concentration of limonene in orange
peel, with average efficiencies of 22%, 44% and 100% for the biological
treatment, steam distillation and ethanol extraction, respectively. By-products
from limonene biodegradation by fungi exhibited an inhibitory effect also, not
making interesting the biological pretreatment. The methane potential and
production rate of the treated orange peel increased significantly after applying
the recovery strategies, which separated and recovered simultaneously other
inhibitory components of the citrus essential oil. Apart from the high recovery
efficiency of the ethanol extraction process, it presented a favourable energy
balance.
PMID- 27486154
TI - Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical
Guidelines for the Management of Adults with Major Depressive Disorder: Section
4. Neurostimulation Treatments.
AB - BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT)
conducted a revision of the 2009 guidelines by updating the evidence and
recommendations. The scope of the 2016 guidelines remains the management of major
depressive disorder (MDD) in adults, with a target audience of psychiatrists and
other mental health professionals. METHODS: Using the question-answer format, we
conducted a systematic literature search focusing on systematic reviews and meta
analyses. Evidence was graded using CANMAT-defined criteria for level of
evidence. Recommendations for lines of treatment were based on the quality of
evidence and clinical expert consensus. "Neurostimulation Treatments" is the
fourth of six sections of the 2016 guidelines. RESULTS: Evidence-informed
responses were developed for 31 questions for 6 neurostimulation modalities: 1)
transcranial direct current stimulation (tDCS), 2) repetitive transcranial
magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic
seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain
stimulation (DBS). Most of the neurostimulation treatments have been investigated
in patients with varying degrees of treatment resistance. CONCLUSIONS: There is
increasing evidence for efficacy, tolerability, and safety of neurostimulation
treatments. rTMS is now a first-line recommendation for patients with MDD who
have failed at least 1 antidepressant. ECT remains a second-line treatment for
patients with treatment-resistant depression, although in some situations, it may
be considered first line. Third-line recommendations include tDCS and VNS. MST
and DBS are still considered investigational treatments.
PMID- 27486157
TI - Evaluation of a buried vertical well leachate recirculation system for municipal
solid waste landfills.
AB - Vertical liquids addition systems have been used at municipal landfills as a
leachate management method and to enhance biostabilization of waste. Drawbacks of
these systems include a limitation on pressurized injection and the occurrence of
seepage. A novel vertical well system that employed buried wells constructed
below a lift of compacted waste was operated for 153 days at a landfill in
Florida, USA. The system included 54 wells installed in six clusters of nine
wells connected with a horizontally-oriented manifold system. A cumulative volume
of 8430 m3 of leachate was added intermittently into the well clusters over the
duration of the project with no incidence of surface seeps. Achievable average
flow rates ranged from 9.3 * 10-4 m3 s-1 to 14.2 * 10-4 m3 s-1, which was similar
to or greater than flow rates achieved in a previous study using traditional
vertical wells at the same landfill site. The results demonstrated that
pressurized liquids addition in vertical wells at municipal solid waste landfills
can be achieved while avoiding typical operational and maintenance issues
associated with seeps.
PMID- 27486158
TI - How Melanoma Resists PD-1 Blockade.
AB - Researchers at the University of California, Los Angeles, have shed light on
mechanisms by which melanoma cells become resistant to PD-1 blockade with
pembrolizumab. One mechanism involves loss-of-function mutations in JAK1 or JAK2
that abolish interferon-gamma signaling; the other involves a truncating mutation
in B2M that results in defective antigen presentation.
PMID- 27486159
TI - Vascular age calculation and equivalent risk factors in HIV-infected patients
obtained from the D:A:D risk equation.
AB - BACKGROUND: Vascular age is a concept that represents the hypothetical age of the
cardiovascular system and might be an alternative way of expressing the
cardiovascular risk of a patient. The Data Collection on Adverse Effects of Anti
HIV Drugs Study (D:A:D) developed a cardiovascular risk equation from a
population of HIV-infected patients, incorporating exposure to individual
antiretroviral therapy drugs and traditional classic cardiovascular risk factors.
OBJECTIVES: The aim of this study was to determine the vascular age calculated
from the D:A:D equation, for HIV infected patients. METHODS: Vascular age was
calculated according to its definition by using the D:A:D equation. The Poisson
regression model used in the D:A:D equation is an exponential model to calculate
the vascular age to match the exponent of the equation with the factors of a
patient with the exponent of a subject with controlled risk factors. RESULTS: We
obtained an equation that allows calculating the vascular age of a patient
considering cardiovascular risk factors listed in the same D:A:D equation. From
the equation, we have built a table for easy calculation of the vascular age and
a table of cardiovascular risk equivalents. CONCLUSIONS: Vascular age is a new
concept derived from Framingham risk tables that can be calculated with other
risk scales, such as D:A:D for HIV patients. The calculation of vascular age in
HIV patients could be a useful tool for communicating cardiovascular risk and to
improve the control of modifiable risk factors.
PMID- 27486160
TI - Assessment of Fever Advisory Cards (FACs) as an Initiative to Improve Febrile
Neutropenia Management in a Regional Cancer Center Emergency Department.
AB - PURPOSE: We aimed to improve the time to antibiotics (TTA) for patients treated
with chemotherapy who present to the emergency department (ED) with febrile
neutropenia (FN) by using standardized fever advisory cards (FACs). METHODS:
Patients treated with chemotherapy who visited the ED at the Peel Regional Cancer
Center in Ontario, Canada, with suspected FN were identified, before (April 2012
to March 2013) and after (October 2013 to March 2014) FAC implementation. The
primary outcome of interest was TTA. Additional process measures included
Canadian Triage and Acuity Scale score, time to physician assessment, and FAC
compliance. Outcomes were analyzed with descriptive statistics and control charts
to determine whether the change in primary measures were within statistical
control over time. RESULTS: Between the pre-FAC cohort (n = 239) and post-FAC
cohort (n = 69), TTA did not change significantly post-FACs (195 v 244 min, P =
.09), with monthly averages demonstrating normal variation by statistical process
control methodology. The introduction of FACs increased the percentage of
patients with correctly assigned Canadian Triage and Acuity Scale scores (87% v
100%) but did not affect time to physician assessment. Compliance with FACs among
patients was not ideal, with only 62.5% using them as intended. CONCLUSION: The
distribution of FACs was associated with an improved incidence of correct FN
triaging but did not demonstrate a meaningful improvement in the quality of FN
management. This may be explained by FAC use among patients not being ideal. Next
steps in the continued effort toward high-quality FN care include redesign of
FACs, reinforcement of provider and patient education, and ED outreach.
PMID- 27486161
TI - Biochemistry, function, and deficiency of vitamin B12 in Caenorhabditis elegans.
AB - Caenorhabditis elegans is a nematode that has been widely used as an animal for
investigation of diverse biological phenomena. Vitamin B12 is essential for the
growth of this worm, which contains two cobalamin-dependent enzymes,
methylmalonyl-CoA mutase and methionine synthase. A full complement of gene
homologs encoding the enzymes associated with the mammalian intercellular
metabolic processes of vitamin B12 is identified in the genome of C elegans
However, this worm has no orthologs of the vitamin B12-binders that participate
in human intestinal absorption and blood circulation. When the worm is treated
with a vitamin B12-deficient diet for five generations (15 days), it readily
develops vitamin B12 deficiency, which induces worm phenotypes (infertility,
delayed growth, and shorter lifespan) that resemble the symptoms of mammalian
vitamin B12 deficiency. Such phenotypes associated with vitamin B12 deficiency
were readily induced in the worm.
PMID- 27486163
TI - Management of Hypertension in Patients With Mild to Moderate Aortic Stenosis:
Navigating the SEAS.
PMID- 27486162
TI - Peptidomimetic Targeting of Cavbeta2 Overcomes Dysregulation of the L-Type
Calcium Channel Density and Recovers Cardiac Function.
AB - BACKGROUND: L-type calcium channels (LTCCs) play important roles in regulating
cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to
and density at the cell surface. Factors influencing the expression, half-life,
subcellular trafficking, and gating of LTCCs are therefore critically involved in
conditions of cardiac physiology and disease. METHODS: Yeast 2-hybrid screenings,
biochemical and molecular evaluations, protein interaction assays, fluorescence
microscopy, structural molecular modeling, and functional studies were used to
investigate the molecular mechanisms through which the LTCC Cavbeta2 chaperone
regulates channel density at the plasma membrane. RESULTS: On the basis of our
previous results, we found a direct linear correlation between the total amount
of the LTCC pore-forming Cavalpha1.2 and the Akt-dependent phosphorylation status
of Cavbeta2 both in a mouse model of diabetic cardiac disease and in 6 diabetic
and 7 nondiabetic cardiomyopathy patients with aortic stenosis undergoing aortic
valve replacement. Mechanistically, we demonstrate that a conformational change
in Cavbeta2 triggered by Akt phosphorylation increases LTCC density at the
cardiac plasma membrane, and thus the inward calcium current, through a complex
pathway involving reduction of Cavalpha1.2 retrograde trafficking and protein
degradation through the prevention of dynamin-mediated LTCC endocytosis;
promotion of Cavalpha1.2 anterograde trafficking by blocking Kir/Gem-dependent
sequestration of Cavbeta2, thus facilitating the chaperoning of Cavalpha1.2; and
promotion of Cavalpha1.2 transcription by the prevention of Kir/Gem-mediated
shuttling of Cavbeta2 to the nucleus, where it limits the transcription of
Cavalpha1.2 through recruitment of the heterochromatin protein 1gamma epigenetic
repressor to the Cacna1c promoter. On the basis of this mechanism, we developed a
novel mimetic peptide that, through targeting of Cavbeta2, corrects LTCC life
cycle alterations, facilitating the proper function of cardiac cells. Delivery of
mimetic peptide into a mouse model of diabetic cardiac disease associated with
LTCC abnormalities restored impaired calcium balance and recovered cardiac
function. CONCLUSIONS: We have uncovered novel mechanisms modulating LTCC
trafficking and life cycle and provide proof of concept for the use of Cavbeta2
mimetic peptide as a novel therapeutic tool for the improvement of cardiac
conditions correlated with alterations in LTCC levels and function.
PMID- 27486165
TI - Advanced Practice Nursing: A Special Issue.
PMID- 27486166
TI - Try-It-On: Experiential Learning of Holistic Stress Management in a Graduate
Nursing Curriculum.
PMID- 27486164
TI - Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve
Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS).
AB - BACKGROUND: Evidence for treating hypertension in patients with asymptomatic
aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin
Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be
optimal. METHODS: A total of 1767 patients with asymptomatic aortic stenosis and
no manifest atherosclerotic disease were analyzed. Outcomes were all-cause
mortality, cardiovascular death, heart failure, stroke, myocardial infarction,
and aortic valve replacement. BP was analyzed in Cox models as the cumulative
average of serially measured BP and a time-varying covariate. RESULTS: The
incidence of all-cause mortality was highest for average follow-up systolic BP
>=160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1-6.0) and
lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95%
CI, 1.6-2.6). In multivariable analysis, all-cause mortality was associated with
average systolic BP <120 mm Hg (hazard ratio [HR], 3.4; 95% CI, 1.9-6.1),
diastolic BP >=90 mm Hg (HR, 1.8; 95% CI, 1.1-2.9), and pulse pressure <50 mm Hg
(HR, 1.8; 95% CI, 1.1-2.9), with systolic BP of 120 to 139 mm Hg, diastolic BP of
70 to 79 mm Hg, and pulse pressure of 60 to 69 mm Hg taken as reference. Low
systolic and diastolic BPs increased risk in patients with moderate aortic
stenosis. With a time-varying systolic BP from 130 to 139 mm Hg used as
reference, mortality was increased for systolic BP >=160 mm Hg (HR, 1.7; P=0.033)
and BP of 120 to 129 mm Hg (HR, 1.6; P=0.039). CONCLUSIONS: Optimal BP seems to
be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these
patients with asymptomatic aortic stenosis and no manifest atherosclerotic
disease or diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT00092677.
PMID- 27486167
TI - Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based
Case-Control Study.
AB - BACKGROUND AND PURPOSE: To elucidate the predictors of antidepressant use after
subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a
population-based cohort with matched controls. METHODS: The Kuopio sIA database
includes all unruptured and ruptured sIA cases admitted to the Kuopio University
Hospital from its defined catchment population in Eastern Finland, with 3 matched
controls for each patient. The use of all prescribed medicines has been fused
from the Finnish national registry of prescribed medicines. In the present study,
2 or more purchases of antidepressant medication indicated antidepressant use.
The risk factors of the antidepressant use were analyzed in 940 patients alive 12
months after sIA-SAH, and the classification tree analysis was used to create a
predicting model for antidepressant use after sIA-SAH. RESULTS: The 940 12-month
survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6;
95% confidence interval, 2.2-3.1) than their 2676 matched controls (29% versus
14%). Classification tree analysis, based on independent risk factors, was used
for the best prediction model of antidepressant use after sIA-SAH. Modified
Rankin Scale until 12 months was the most potent predictor, followed by condition
(Hunt and Hess Scale) and age on admission for sIA-SAH. CONCLUSIONS: The sIA-SAH
survivors use significantly more often antidepressants, indicative of depression,
than their matched population controls. Even with a seemingly good recovery
(modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a
significant risk of depression requiring antidepressant medication.
PMID- 27486168
TI - Response by Hastrup and Andersen to Letter Regarding Article, "Prehospital Acute
Stroke Severity Scale to Predict Large Artery Occlusion: Design and Comparison
With Other Scales".
PMID- 27486169
TI - Letter by Hastrup et al Regarding Article, "Clinical Scales Do Not Reliably
Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion".
PMID- 27486170
TI - Homozygous ALDH2*2 Is an Independent Risk Factor for Ischemic Stroke in Taiwanese
Men.
AB - BACKGROUND AND PURPOSE: The *2 allele of the aldehyde dehydrogenase 2 gene
(ALDH2) is the most common variant in Asian populations. The variant resulting in
enzyme dysfunction was highly related to coronary artery disease. Recently,
genome-wide association studies also discovered that the 12q24 locus near ALDH2
gene was associated with hypertension and ischemic stroke. This study intended to
further investigate whether the above variant of ALDH2 increases the risk for
ischemic stroke in Taiwanese. METHODS: A case-control study was conducted on 914
patients with acute ischemic stroke and 746 nonstroke controls. Polymerase chain
reaction and sequencing were used to identify the ALDH2 genotype. Vascular risk
factors, stroke subtypes, vascular stenosis, and stroke outcomes were analyzed.
RESULTS: ALDH2 genotypes differed significantly between male controls (*1/*1
versus *1/*2 versus *2/*2=53.8% versus 39.9% versus 6.4%) and male patients with
ischemic stroke (*1/*1 versus *1/*2 versus *2/*2=51.5% versus 37.3% versus 11.2%;
P=0.048). No significant difference was found between groups for female patients
(P=0.228). Multivariate logistic regression analysis revealed that the ALDH2*2/*2
genotype was an independent risk factor for ischemic stroke in male patients
(odds ratio, 1.93 [95% confidence interval, 1.07-3.46]; P=0.028). Further
analysis of men with ischemic stroke demonstrated that the polymorphism of ALDH2
was not related to vascular risk factors, severity of vascular atherosclerosis,
stroke subtypes, and stroke functional outcomes. CONCLUSIONS: The study
demonstrated that ALDH2*2/*2 may be an independent risk factor for ischemic
stroke in Taiwanese men, but not in Taiwanese women.
PMID- 27486171
TI - Response by Maier and Turc to Letter Regarding Article, "Clinical Scales Do Not
Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion".
PMID- 27486172
TI - Letter by Heldner et al Regarding Article, "Prehospital Acute Stroke Severity
Scale to Predict Large Artery Occlusion: Design and Comparison With Other
Scales".
PMID- 27486173
TI - Aspiration Thrombectomy After Intravenous Alteplase Versus Intravenous Alteplase
Alone.
AB - BACKGROUND AND PURPOSE: Thrombectomy, primarily with stent retrievers with or
without adjunctive aspiration, provided clinical benefit across multiple
prospective randomized trials. Whether this benefit is exclusive to stent
retrievers is unclear. METHODS: THERAPY (The Randomized, Concurrent Controlled
Trial to Assess the Penumbra System's Safety and Effectiveness in the Treatment
of Acute Stroke; NCT01429350) was an international, multicenter, prospective,
randomized (1:1), open label, blinded end point evaluation, concurrent controlled
clinical trial of aspiration thrombectomy after intravenous alteplase (IAT)
administration compared with intravenous-alteplase alone in patients with large
vessel ischemic stroke because of a thrombus length of >=8 mm. The primary
efficacy end point was the percent of patients achieving independence at 90 days
(modified Rankin Scale score, 0-2; intention-to-treat analysis). The primary
safety end point was the rate of severe adverse events (SAEs) by 90 days (as
treated analysis). Patients were randomized 1:1 across 36 centers in 2 countries
(United States and Germany). RESULTS: Enrollment was halted after 108 (55 IAT and
53 intravenous) patients (of 692 planned) because of external evidence of the
added benefit of endovascular therapy to intravenous-alteplase alone. Functional
independence was achieved in 38% IAT and 30% intravenous intention-to-treat
groups (P=0.52). Intention-to-treat ordinal modified Rankin Scale odds ratio was
1.76 (95% confidence interval, 0.86-3.59; P=0.12) in favor of IAT. Secondary
efficacy analyses all demonstrated a consistent direction of effect toward
benefit of IAT. No differences in symptomatic intracranial hemorrhage rates (9.3%
IAT versus 9.7% intravenous, P=1.0) or 90-day mortality (IAT: 12% versus
intravenous: 23.9%, P=0.18) were observed. CONCLUSIONS: THERAPY did not achieve
its primary end point in this underpowered sample. Directions of effect for all
prespecified outcomes were both internally and externally consistent toward
benefit. It is possible that an alternate method of thrombectomy, primary
aspiration, will benefit selected patients harboring large vessel occlusions.
Further study on this topic is indicated. CLINICAL TRIAL REGISTRATION: URL:
http://www.clinicaltrials.gov. Unique identifier: NCT01429350.
PMID- 27486174
TI - The Dual Inhibition of RNA Pol I Transcription and PIM Kinase as a New
Therapeutic Approach to Treat Advanced Prostate Cancer.
AB - PURPOSE: The MYC oncogene is frequently overexpressed in prostate cancer.
Upregulation of ribosome biogenesis and function is characteristic of MYC-driven
tumors. In addition, PIM kinases activate MYC signaling and mRNA translation in
prostate cancer and cooperate with MYC to accelerate tumorigenesis. Here, we
investigate the efficacy of a single and dual approach targeting ribosome
biogenesis and function to treat prostate cancer. EXPERIMENTAL DESIGN: The
inhibition of ribosomal RNA (rRNA) synthesis with CX-5461, a potent, selective,
and orally bioavailable inhibitor of RNA polymerase I (Pol I) transcription, has
been successfully exploited therapeutically but only in models of hematologic
malignancy. CX-5461 and CX-6258, a pan-PIM kinase inhibitor, were tested alone
and in combination in prostate cancer cell lines, in Hi-MYC- and PTEN-deficient
mouse models and in patient-derived xenografts (PDX) of metastatic tissue
obtained from a patient with castration-resistant prostate cancer. RESULTS: CX
5461 inhibited anchorage-independent growth and induced cell-cycle arrest in
prostate cancer cell lines at nanomolar concentrations. Oral administration of 50
mg/kg CX-5461 induced TP53 expression and activity and reduced proliferation
(MKI67) and invasion (loss of ductal actin) in Hi-MYC tumors, but not in PTEN
null (low MYC) tumors. While 100 mg/kg CX-6258 showed limited effect alone, its
combination with CX-5461 further suppressed proliferation and dramatically
reduced large invasive lesions in both models. This rational combination strategy
significantly inhibited proliferation and induced cell death in PDX of prostate
cancer. CONCLUSIONS: Our results demonstrate preclinical efficacy of targeting
the ribosome at multiple levels and provide a new approach for the treatment of
prostate cancer. Clin Cancer Res; 22(22); 5539-52. (c)2016 AACR.
PMID- 27486176
TI - Regression of Chemotherapy-Resistant Polymerase epsilon (POLE) Ultra-Mutated and
MSH6 Hyper-Mutated Endometrial Tumors with Nivolumab.
AB - PURPOSE: The management of endometrial carcinoma no longer amenable to treatment
with surgery or radiotherapy has not improved significantly with modern
chemotherapy. Alternative therapeutic options are desperately needed.
EXPERIMENTAL DESIGN: We describe 2 heavily pretreated patients with recurrent
disease refractory to surgery, radiotherapy, and chemotherapy who were treated
with the anti-PD-1 immune checkpoint inhibitor nivolumab. RESULTS: Patient #1
harbored an ultra-mutated tumor (mutation load/MB = 117.3, total mutations =
4,660) driven by mutation in the exonuclease domain of the DNA polymerase epsilon
gene. Patient #2 harbored a hyper-mutated tumor (mutation load/MB = 33.5, total
mutations = 1,037) due to a germinal MSH6 gene mutation. Both patients
demonstrated a remarkable clinical response to the anti-PD-1 immune checkpoint
inhibitor nivolumab. Patients' clinical responses remain unchanged at the time of
the writing of this report, with no grade 3 or higher side effects reported to
date. CONCLUSIONS: Anti-PD-1 inhibitors represent a novel treatment option for
recurrent/metastatic, ultra/hyper-mutated human tumors refractory to salvage
treatment. Clin Cancer Res; 22(23); 5682-7. (c)2016 AACRSee related commentary by
Piulats and Matias-Guiu, p. 5623.
PMID- 27486175
TI - Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1-Associated
Adult T-cell Leukemia/lymphoma.
AB - PURPOSE: Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are
limited with unsatisfactory results, thereby warranting development of novel
therapies. This study investigated antitumor activity and toxicity of alemtuzumab
with regard to response, duration of response, progression-free survival, and
overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)
associated ATL. EXPERIMENTAL DESIGN: Twenty-nine patients with chronic, acute,
and lymphomatous types of ATL were enrolled in a single-institution,
nonrandomized, open-label phase II trial wherein patients received intravenous
alemtuzumab 30 mg three times weekly for a maximum of 12 weeks. RESULTS: Twenty
nine patients were evaluable for response and toxicity. The overall objective
response was 15 of 29 patients [95% confidence interval (CI), 32.5%-70.6%]. The
15 patients who responded manifested a median time to response of 1.1 months.
Median response duration was 1.4 months for the whole group and 14.5 months among
responders. Median progression-free survival was 2.0 months. Median overall
survival was 5.9 months. The most common adverse events were 2 with vasovagal
episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%) grade 3 and
(17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia
(24%), and thrombocytopenia (10%). All patients developed cytomegalovirus
antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy.
Grade 3 or 4 infections were reported in 4 (14%) of patients. CONCLUSIONS:
Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with
acceptable toxicity, but with short duration of responses. These studies support
inclusion of alemtuzumab in novel multidrug therapies for ATL. Clin Cancer Res;
23(1); 35-42. (c)2016 AACR.
PMID- 27486178
TI - Evidence That Classroom-Based Behavioral Interventions Reduce Pregnancy-Related
School Dropout Among Nairobi Adolescents.
AB - PURPOSE: To evaluate the effect of behavioral, empowerment-focused interventions
on the incidence of pregnancy-related school dropout among girls in Nairobi's
informal settlements. METHOD: Retrospective data on pregnancy-related school
dropout from two cohorts were analyzed using a matched-pairs quasi-experimental
design. The primary outcome was the change in the number of school dropouts due
to pregnancy from 1 year before to 1 year after the interventions. RESULTS:
Annual incidence of school dropout due to pregnancy decreased by 46% in the
intervention schools (from 3.9% at baseline to 2.1% at follow-up), whereas the
comparison schools remained essentially unchanged ( p < .029). Sensitivity
analysis shows that the findings are robust to small levels of unobserved bias.
CONCLUSIONS: Results suggest that these behavioral interventions significantly
reduced the number of school dropouts due to pregnancy. As there are limited
promising studies on behavioral interventions that decrease adolescent pregnancy
in low-income settings, this intervention may be an important addition to this
toolkit.
PMID- 27486177
TI - Evaluating Acetate Metabolism for Imaging and Targeting in Multiple Myeloma.
AB - PURPOSE: We hypothesized that in multiple myeloma cells (MMC), high membrane
biosynthesis will induce acetate uptake in vitro and in vivo Here, we studied
acetate metabolism and targeting in MMC in vitro and tested the efficacy of 11C
acetate-positron emission tomography (PET) to detect and quantitatively image
myeloma treatment response in vivo EXPERIMENTAL DESIGN: Acetate fate tracking
using 13C-edited-1H NMR (nuclear magnetic resonance) was performed to study in
vitro acetate uptake and metabolism in MMC. Effects of pharmacological modulation
of acetate transport or acetate incorporation into lipids on MMC cell survival
and viability were assessed. Preclinical mouse MM models of subcutaneous and bone
tumors were evaluated using 11C-acetate-PET/CT imaging and tissue
biodistribution. RESULTS: In vitro, NMR showed significant uptake of acetate by
MMC and acetate incorporation into intracellular metabolites and membrane lipids.
Inhibition of lipid synthesis and acetate transport was toxic to MMC, while
sparing resident bone cells or normal B cells. In vivo, 11C-acetate uptake by PET
imaging was significantly enhanced in subcutaneous and bone MMC tumors compared
with unaffected bone or muscle tissue. Likewise, 11C-acetate uptake was
significantly reduced in MM tumors after treatment. CONCLUSIONS: Uptake of
acetate from the extracellular environment was enhanced in MMC and was critical
to cellular viability. 11C-Acetate-PET detected the presence of myeloma cells in
vivo, including uptake in intramedullary bone disease. 11C-Acetate-PET also
detected response to therapy in vivo Our data suggested that acetate metabolism
and incorporation into lipids was crucial to MM cell biology and that 11C-acetate
PET is a promising imaging modality for MM. Clin Cancer Res; 23(2); 416-29.
(c)2016 AACR.
PMID- 27486180
TI - Maximum Likelihood Implementation of an Isolation-with-Migration Model for Three
Species.
AB - We develop a maximum likelihood (ML) method for estimating migration rates
between species using genomic sequence data. A species tree is used to
accommodate the phylogenetic relationships among three species, allowing for
migration between the two sister species, while the third species is used as an
out-group. A Markov chain characterization of the genealogical process of
coalescence and migration is used to integrate out the migration histories at
each locus analytically, whereas Gaussian quadrature is used to integrate over
the coalescent times on each genealogical tree numerically. This is an extension
of our early implementation of the symmetrical isolation-with-migration model for
three species to accommodate arbitrary loci with two or three sequences per locus
and to allow asymmetrical migration rates. Our implementation can accommodate
tens of thousands of loci, making it feasible to analyze genome-scale data sets
to test for gene flow. We calculate the posterior probabilities of gene trees at
individual loci to identify genomic regions that are likely to have been
transferred between species due to gene flow. We conduct a simulation study to
examine the statistical properties of the likelihood ratio test for gene flow
between the two in-group species and of the ML estimates of model parameters such
as the migration rate. Inclusion of data from a third out-group species is found
to increase dramatically the power of the test and the precision of parameter
estimation. We compiled and analyzed several genomic data sets from the
Drosophila fruit flies. Our analyses suggest no migration from D. melanogaster to
D. simulans, and a significant amount of gene flow from D. simulans to D.
melanogaster, at the rate of ~0.02 migrant individuals per generation. We discuss
the utility of the multispecies coalescent model for species tree estimation,
accounting for incomplete lineage sorting and migration.
PMID- 27486179
TI - Development of the System for Observing Student Movement in Academic Routines and
Transitions (SOSMART).
AB - National attention on whole-of-school approaches to decrease children's sedentary
behavior and increase physical activity includes movement integration (MI) in
classrooms. The purpose of this study was to describe instrument development,
reliability, and validity of the System for Observing Student Movement in
Academic Routines and Transitions (SOSMART), designed to assess MI in elementary
classrooms. An a priori conceptual framework was developed based on existing
literature. The framework was expanded/refined using videos from elementary
classrooms and a Delphi survey. The survey, sent to 85 experts, yielded a 38%
response rate. The final system includes 11 MI variables (three categories of
teacher variables, two categories of student variables) and uses a 20-second
continuous interval recording format. Reliability and validity data were
collected in 12 classrooms across four elementary schools. Instrument reliability
was tested using interval-by-interval percentage agreement for each category.
Construct validity was tested by estimating multilevel random effects logistic
regression models comparing student accelerometer derived activity with the
presence/absence of each MI variable. Intraobserver reliability resulted in 97.5%
agreement and exceeded 80% on all variables. Construct validity was supported for
8 out of 11 MI variables. SOSMART can provide valid, reliable, and objective data
about MI in elementary schools.
PMID- 27486181
TI - SpeciesGeoCoder: Fast Categorization of Species Occurrences for Analyses of
Biodiversity, Biogeography, Ecology, and Evolution.
AB - Understanding the patterns and processes underlying the uneven distribution of
biodiversity across space constitutes a major scientific challenge in systematic
biology and biogeography, which largely relies on effectively mapping and making
sense of rapidly increasing species occurrence data. There is thus an urgent need
for making the process of coding species into spatial units faster, automated,
transparent, and reproducible. Here we present SpeciesGeoCoder, an open-source
software package written in Python and R, that allows for easy coding of species
into user-defined operational units. These units may be of any size and be purely
spatial (i.e., polygons) such as countries and states, conservation areas,
biomes, islands, biodiversity hotspots, and areas of endemism, but may also
include elevation ranges. This flexibility allows scoring species into complex
categories, such as those encountered in topographically and ecologically
heterogeneous landscapes. In addition, SpeciesGeoCoder can be used to facilitate
sorting and cleaning of occurrence data obtained from online databases, and for
testing the impact of incorrect identification of specimens on the spatial coding
of species. The various outputs of SpeciesGeoCoder include quantitative
biodiversity statistics, global and local distribution maps, and files that can
be used directly in many phylogeny-based applications for ancestral range
reconstruction, investigations of biome evolution, and other comparative methods.
Our simulations indicate that even datasets containing hundreds of millions of
records can be analyzed in relatively short time using a standard computer. We
exemplify the use of SpeciesGeoCoder by inferring the historical dispersal of
birds across the Isthmus of Panama, showing that lowland species crossed the
Isthmus about twice as frequently as montane species with a marked increase in
the number of dispersals during the last 10 million years. [ancestral area
reconstruction; biodiversity patterns; ecology; evolution; point in polygon;
species distribution data.].
PMID- 27486183
TI - The design and application of an e-health readiness assessment tool.
AB - BACKGROUND: To date, several models have been developed to evaluate e-health
readiness in healthcare organisations; however, no specific tool has been
designed to assess or measure e-health readiness. OBJECTIVE: The aim of this
research was to design an e-health readiness assessment tool and to apply this
tool to two Iranian hospitals to assess their readiness for the implementation of
e-health. METHOD: The study, which was undertaken in 2012, consisted of three
phases: (i) review of existing models of e-health; (ii) design of an e-health
readiness assessment tool; and (iii) trial of the assessment tool in two Iranian
hospitals. Phase 1 consisted of a literature review that informed the development
of the tool. In phase 2, we developed an e-health readiness assessment tool with
feedback using two questionnaires from 40 employees from two teaching hospitals
in Iran. In phase 3, we applied the tool to the same two Iranian teaching
hospitals. Participants who completed the questionnaires were from management,
health information technology, medical and nursing backgrounds and were familiar
with e-health. A purposive sampling method was used to invite them to take part
in the study. Data from the questionnaires were analysed using factor analysis
and descriptive statistics. RESULTS: Five dimensions and twenty-one indices were
selected to be included in the e-health readiness tool. The 5 dimensions and
their relative importance were e-health readiness (16%), information and
communication technology (ICT) functions (15%), environmental readiness (20%),
human resources readiness (29%) and ICT readiness (20%). The total e-health
readiness scores for hospital A and hospital B were 0.22 and 0.4, respectively (a
score of 1 is the ideal). CONCLUSION: It is important to assess the e-health
readiness of hospitals to save time and money and be able to better prepare for
ICT implementations. The e-health readiness assessment tool provides a relatively
simple method for assessing hospitals and provides essential information to
assist healthcare facilities focus preparations and planning for e-health
implementations.
PMID- 27486184
TI - Patient perspectives on a personally controlled electronic health record used in
regional Australia.
AB - BACKGROUND: Personally controlled electronic health records (PCEHRs) are being
implemented throughout Australia; yet few studies have investigated patients'
experiences of using a PCEHR. AIM: To explore patients' experiences and
perspectives of using a locally developed PCEHR implemented in an Australian
health service. METHOD: Twelve patients completed individual semi-structured
telephone interviews, which underwent inductive analysis. RESULTS: Participants
described two main interdependent advantages of PCEHRs: improved quality of
healthcare through better information sharing and enhanced patient capacity for
self-management. To realise these advantages, widespread acceptance and use of
PCEHRs by healthcare providers is required, and PCEHRs need to be simple to use
and accessible. CONCLUSION: PCEHRs can produce tangible benefits for patients.
However, maximum benefits will be realised when PCEHRs contain a complete
collection of relevant health information and are carefully designed for easy
use.
PMID- 27486185
TI - Utilizing health records to characterize obesity, comorbidities, and health-care
services in one human service agency in the United States.
AB - US surveys report higher prevalence of obesity in adults with intellectual
disability. Health records of 40 adults with intellectual disability were
retrospectively reviewed for data on health status, problem lists with
International Classification of Diseases, Ninth Revision codes, medication lists,
and health encounters over 18 months. Mean age was 49.5 years, 53% were males.
Prevalence of overweight, obese, and morbidly obese was 28%, 58%, and 23%,
respectively. Primary diagnosis was intellectual disability (50% mild, 33%
moderate, 10% severe, and 8% profound), 85% had mental health disorders (67.5%
with affective or mood and 42.5% had anxiety disorders). On average, residents
consumed 2.63 psychotropic medications daily with additional 5.75 medications for
axis 3 diagnoses and made 39.2 health visits over past 18 months. Our analysis
supports increased prevalence of overweight/obesity, higher comorbidities, dual
psychiatric diagnosis, substantial medication consumption, and higher utilization
of health-care services in adults with intellectual disabilities. Targeted health
interventions are therefore essential to improve their health and quality of
life.
PMID- 27486186
TI - All voices matter in experience design: A commitment to action in engaging
patient and family voice.
AB - This article intends to frame the broader concept of experience design and the
engagement of patient and family voice, reinforcing how truly aligned healthcare
professionals are not only on the value of this work but also in understanding
the benefits of it. When addressing the idea of design, it is important to look
at the broadest possible construct and consider the engagement of patient and
family voices in healthcare operational efforts, not as passive advisors but as
active participants in data gathering, providing input, and with actual decision
making. The article offers engagement is not just part of process, facility, or
experience design but must be part of the decisions made in how organizations in
healthcare today are built, led, and sustained, fundamentally reinforcing our
opportunity in healthcare is to focus on overall experience with purpose and
intention. This commitment is what will lead to the outcomes all ultimately hope
to achieve.
PMID- 27486187
TI - DamX Controls Reversible Cell Morphology Switching in Uropathogenic Escherichia
coli.
AB - The ability to change cell morphology is an advantageous characteristic adopted
by multiple pathogenic bacteria in order to evade host immune detection and
assault during infection. Uropathogenic Escherichia coli (UPEC) exhibits such
cellular dynamics and has been shown to transition through a series of distinct
morphological phenotypes during a urinary tract infection. Here, we report the
first systematic spatio-temporal gene expression analysis of the UPEC transition
through these phenotypes by using a flow chamber-based in vitro infection model
that simulates conditions in the bladder. This analysis revealed a novel
association between the cell division gene damX and reversible UPEC
filamentation. We demonstrate a lack of reversible bacterial filamentation in a
damX deletion mutant in vitro and absence of a filamentous response by this
mutant in a murine model of cystitis. While deletion of damX abrogated UPEC
filamentation and secondary surface colonization in tissue culture and in mouse
infections, transient overexpression of damX resulted in reversible UPEC
filamentation. In this study, we identify a hitherto-unknown damX-mediated
mechanism underlying UPEC morphotypical switching. Murine infection studies
showed that DamX is essential for establishment of a robust urinary tract
infection, thus emphasizing its role as a mediator of virulence. Our study
demonstrates the value of an in vitro methodology, in which uroepithelium
infection is closely simulated, when undertaking targeted investigations that are
challenging to perform in animal infection models. IMPORTANCE: Urinary tract
infections (UTIs) are most often caused by uropathogenic Escherichia coli (UPEC)
and account for a considerable health care burden. UPEC exhibits a dynamic
lifestyle in the course of infection, in which the bacterium transiently adopts
alternative morphologies ranging from rod shaped to coccoid and filamentous,
rendering it better at immune evasion and host epithelium adhesion. This penchant
for morphotype switching might in large measure account for UPEC's success as a
pathogen. In aiming to uncover genes underlying the phenomenon of UPEC morphotype
switching, this study identifies damX, a cell division gene, as a mediator of
reversible filamentation during UTI. DamX-mediated filamentation represents an
additional pathway for bacterial cell shape control, an alternative to SulA
mediated FtsZ sequestration during E. coli uropathogenesis, and hence represents
a potential target for combating UTI.
PMID- 27486188
TI - Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among
Candida glabrata Clinical Strains Associated with In Vivo Persistence.
AB - Candida glabrata causes persistent infections in patients treated with
fluconazole and often acquires resistance following exposure to the drug. Here we
found that clinical strains of C. glabrata exhibit cell-to-cell variation in drug
response (heteroresistance). We used population analysis profiling (PAP) to
assess fluconazole heteroresistance (FLC(HR)) and to ask if it is a binary trait
or a continuous phenotype. Thirty (57.6%) of 52 fluconazole-sensitive clinical C.
glabrata isolates met accepted dichotomous criteria for FLC(HR) However,
quantitative grading of FLC(HR) by using the area under the PAP curve (AUC)
revealed a continuous distribution across a wide range of values, suggesting that
all isolates exhibit some degree of heteroresistance. The AUC correlated with
rhodamine 6G efflux and was associated with upregulation of the CDR1 and PDH1
genes, encoding ATP-binding cassette (ABC) transmembrane transporters, implying
that HetR populations exhibit higher levels of drug efflux. Highly FLC(HR) C.
glabrata was recovered more frequently than nonheteroresistant C. glabrata from
hematogenously infected immunocompetent mice following treatment with high-dose
fluconazole (45.8% versus 15%, P = 0.029). Phylogenetic analysis revealed some
phenotypic clustering but also variations in FLC(HR) within clonal groups,
suggesting both genetic and epigenetic determinants of heteroresistance.
Collectively, these results establish heteroresistance to fluconazole as a graded
phenotype associated with ABC transporter upregulation and fluconazole efflux.
Heteroresistance may explain the propensity of C. glabrata for persistent
infection and the emergence of breakthrough resistance to fluconazole.
IMPORTANCE: Heteroresistance refers to variability in the response to a drug
within a clonal cell population. This phenomenon may have crucial importance for
the way we look at antimicrobial resistance, as heteroresistant strains are not
detected by standard laboratory susceptibility testing and may be associated with
failure of antimicrobial therapy. We describe for the first time heteroresistance
to fluconazole in C. glabrata, a finding that may explain the propensity of this
pathogen to acquire resistance following exposure to fluconazole and to persist
despite treatment. We found that, rather than being a binary all-or-none trait,
heteroresistance was a continuously distributed phenotype associated with
increased expression of genes that encode energy-dependent drug efflux
transporters. Moreover, we show that heteroresistance is associated with failure
of fluconazole to clear infection with C. glabrata Together, these findings
provide an empirical framework for determining and quantifying heteroresistance
in C. glabrata.
PMID- 27486189
TI - Ablation of STAT3 in the B Cell Compartment Restricts Gammaherpesvirus Latency In
Vivo.
AB - A challenging property of gammaherpesviruses is their ability to establish
lifelong persistence. The establishment of latency in B cells is thought to
involve active virus engagement of host signaling pathways. Pathogenic effects of
these viruses during latency or following reactivation can be devastating to the
host. Many cancers, including those associated with members of the
gammaherpesvirus family, Kaposi's sarcoma-associated herpesvirus and Epstein-Barr
virus, express elevated levels of active host signal transducer and activator of
transcription-3 (STAT3). STAT3 is activated by tyrosine phosphorylation in
response to many cytokines and can orchestrate effector responses that include
proliferation, inflammation, metastasis, and developmental programming. However,
the contribution of STAT3 to gammaherpesvirus pathogenesis remains to be
completely understood. This is the first study to have identified STAT3 as a
critical host determinant of the ability of gammaherpesvirus to establish long
term latency in an animal model of disease. Following an acute infection, murine
gammaherpesvirus 68 (MHV68) established latency in resident B cells, but
establishment of latency was dramatically reduced in animals with a B cell
specific STAT3 deletion. The lack of STAT3 in B cells did not impair germinal
center responses for immunoglobulin (Ig) class switching in the spleen and did
not reduce either total or virus-specific IgG titers. Although ablation of STAT3
in B cells did not have a global effect on these assays of B cell function, it
had long-term consequences for the viral load of the host, since virus latency
was reduced at 6 to 8 weeks postinfection. Our findings establish host STAT3 as a
mediator of gammaherpesvirus persistence. IMPORTANCE: The insidious ability of
gammaherpesviruses to establish latent infections can have detrimental
consequences for the host. Identification of host factors that promote viral
latency is essential for understanding latency mechanisms and for therapeutic
interventions. We provide the first evidence that STAT3 expression is needed for
murine gammaherpesvirus 68 to establish latency in primary B cells during an
active immune response to infection. STAT3 deletion in B cells does not impair
adaptive immune control of the virus, but loss of STAT3 in B cells has a long
lasting impact on viral persistence. These results indicate a potential
therapeutic benefit of STAT3 inhibitors for combating gammaherpesvirus latency
and, thereby, associated pathologies.
PMID- 27486190
TI - In Vivo Biotinylation of the Toxoplasma Parasitophorous Vacuole Reveals Novel
Dense Granule Proteins Important for Parasite Growth and Pathogenesis.
AB - Toxoplasma gondii is an obligate intracellular parasite that invades host cells
and replicates within a unique parasitophorous vacuole. To maintain this
intracellular niche, the parasite secretes an array of dense granule proteins
(GRAs) into the nascent parasitophorous vacuole. These GRAs are believed to play
key roles in vacuolar remodeling, nutrient uptake, and immune evasion while the
parasite is replicating within the host cell. Despite the central role of GRAs in
the Toxoplasma life cycle, only a subset of these proteins have been identified,
and many of their roles have not been fully elucidated. In this report, we
utilize the promiscuous biotin ligase BirA* to biotinylate GRA proteins secreted
into the vacuole and then identify those proteins by affinity purification and
mass spectrometry. Using GRA-BirA* fusion proteins as bait, we have identified a
large number of known and candidate GRAs and verified localization of 13 novel
GRA proteins by endogenous gene tagging. We proceeded to functionally
characterize three related GRAs from this group (GRA38, GRA39, and GRA40) by gene
knockout. While Deltagra38 and Deltagra40 parasites showed no altered phenotype,
disruption of GRA39 results in slow-growing parasites that contain striking lipid
deposits in the parasitophorous vacuole, suggesting a role in lipid regulation
that is important for parasite growth. In addition, parasites lacking GRA39
showed dramatically reduced virulence and a lower tissue cyst burden in vivo
Together, the findings from this work reveal a partial vacuolar proteome of T.
gondii and identify a novel GRA that plays a key role in parasite replication and
pathogenesis. IMPORTANCE: Most intracellular pathogens reside inside a membrane
bound vacuole within their host cell that is extensively modified by the pathogen
to optimize intracellular growth and avoid host defenses. In Toxoplasma, this
vacuole is modified by a host of secretory GRA proteins, many of which remain
unidentified. Here we demonstrate that in vivo biotinylation of proximal and
interacting proteins using the promiscuous biotin ligase BirA* is a powerful
approach to rapidly identify vacuolar GRA proteins. We further demonstrate that
one factor identified by this approach, GRA39, plays an important role in the
ability of the parasite to replicate within its host cell and cause disease.
PMID- 27486191
TI - Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic
Fibrosis Lung.
AB - Chronic colonization of the lungs by Pseudomonas aeruginosa is one of the major
causes of morbidity and mortality in cystic fibrosis (CF) patients. To gain
insights into the characteristic biofilm phenotype of P. aeruginosa in the CF
lungs, mimicking the CF lung environment is critical. We previously showed that
growth of the non-CF-adapted P. aeruginosa PAO1 strain in a rotating wall vessel,
a device that simulates the low fluid shear (LS) conditions present in the CF
lung, leads to the formation of in-suspension, self-aggregating biofilms. In the
present study, we determined the phenotypic and transcriptomic changes associated
with the growth of a highly adapted, transmissible P. aeruginosa CF strain in
artificial sputum medium under LS conditions. Robust self-aggregating biofilms
were observed only under LS conditions. Growth under LS conditions resulted in
the upregulation of genes involved in stress response, alginate biosynthesis,
denitrification, glycine betaine biosynthesis, glycerol metabolism, and cell
shape maintenance, while genes involved in phenazine biosynthesis, type VI
secretion, and multidrug efflux were downregulated. In addition, a number of
small RNAs appeared to be involved in the response to shear stress. Finally,
quorum sensing was found to be slightly but significantly affected by shear
stress, resulting in higher production of autoinducer molecules during growth
under high fluid shear (HS) conditions. In summary, our study revealed a way to
modulate the behavior of a highly adapted P. aeruginosa CF strain by means of
introducing shear stress, driving it from a biofilm lifestyle to a more
planktonic lifestyle. IMPORTANCE: Biofilm formation by Pseudomonas aeruginosa is
one of the hallmarks of chronic cystic fibrosis (CF) lung infections. The biofilm
matrix protects this bacterium from antibiotics as well as from the immune
system. Hence, the prevention or reversion of biofilm formation is believed to
have a great impact on treatment of chronic P. aeruginosa CF lung infections. In
the present study, we showed that it is possible to modulate the behavior of a
highly adapted transmissible P. aeruginosa CF isolate at both the transcriptomic
and phenotypic levels by introducing shear stress in a CF-like environment,
driving it from a biofilm to a planktonic lifestyle. Consequently, the results
obtained in this study are of great importance with regard to therapeutic
applications that introduce shear stress in the lungs of CF patients.
PMID- 27486192
TI - Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to
Peptidoglycan in Mycobacterium tuberculosis.
AB - Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has a
unique cell envelope which accounts for its unusual low permeability and
contributes to resistance against common antibiotics. The main structural
elements of the cell wall consist of a cross-linked network of peptidoglycan (PG)
in which some of the muramic acid residues are covalently attached to a complex
polysaccharide, arabinogalactan (AG), via a unique alpha-l-rhamnopyranose-(1->3)
alpha-d-GlcNAc-(1->P) linker unit. While the molecular genetics associated with
PG and AG biosynthetic pathways have been largely delineated, the mechanism by
which these two major pathways converge has remained elusive. In Gram-positive
organisms, the LytR-CpsA-Psr (LCP) family of proteins are responsible for
ligating cell wall teichoic acids to peptidoglycan, through a linker unit that
bears a striking resemblance to that found in mycobacterial arabinogalactan. In
this study, we have identified Rv3267 as a mycobacterial LCP homolog gene that
encodes a phosphotransferase which we have named Lcp1. We demonstrate that lcp1
is an essential gene required for cell viability and show that recombinant Lcp1
is capable of ligating AG to PG in a cell-free radiolabeling assay. IMPORTANCE:
Tuberculosis is an infectious disease caused by the bacterial organism
Mycobacterium tuberculosis Survival of M. tuberculosis rests critically on the
integrity of its unique cell wall; therefore, a better understanding of how the
genes and enzymes involved in cell wall assembly work is fundamental for us to
develop new drugs to treat this disease. In this study, we have identified Lcp1
as an essential phosphotransferase that ligates together arabinogalactan and
peptidoglycan, two crucial cell wall macromolecules found within the
mycobacterial cell wall. The discovery of Lcp1 sheds new light on the final
stages of mycobacterial cell wall assembly and represents a key biosynthetic step
that could be exploited for new anti-TB drug discovery.
PMID- 27486193
TI - The Double-Stranded DNA Virosphere as a Modular Hierarchical Network of Gene
Sharing.
AB - Virus genomes are prone to extensive gene loss, gain, and exchange and share no
universal genes. Therefore, in a broad-scale study of virus evolution, gene and
genome network analyses can complement traditional phylogenetics. We performed an
exhaustive comparative analysis of the genomes of double-stranded DNA (dsDNA)
viruses by using the bipartite network approach and found a robust hierarchical
modularity in the dsDNA virosphere. Bipartite networks consist of two classes of
nodes, with nodes in one class, in this case genomes, being connected via nodes
of the second class, in this case genes. Such a network can be partitioned into
modules that combine nodes from both classes. The bipartite network of dsDNA
viruses includes 19 modules that form 5 major and 3 minor supermodules. Of these
modules, 11 include tailed bacteriophages, reflecting the diversity of this
largest group of viruses. The module analysis quantitatively validates and
refines previously proposed nontrivial evolutionary relationships. An expansive
supermodule combines the large and giant viruses of the putative order
"Megavirales" with diverse moderate-sized viruses and related mobile elements.
All viruses in this supermodule share a distinct morphogenetic tool kit with a
double jelly roll major capsid protein. Herpesviruses and tailed bacteriophages
comprise another supermodule, held together by a distinct set of morphogenetic
proteins centered on the HK97-like major capsid protein. Together, these two
supermodules cover the great majority of currently known dsDNA viruses. We
formally identify a set of 14 viral hallmark genes that comprise the hubs of the
network and account for most of the intermodule connections. IMPORTANCE: Viruses
and related mobile genetic elements are the dominant biological entities on
earth, but their evolution is not sufficiently understood and their
classification is not adequately developed. The key reason is the characteristic
high rate of virus evolution that involves not only sequence change but also
extensive gene loss, gain, and exchange. Therefore, in the study of virus
evolution on a large scale, traditional phylogenetic approaches have limited
applicability and have to be complemented by gene and genome network analyses. We
applied state-of-the art methods of such analysis to reveal robust hierarchical
modularity in the genomes of double-stranded DNA viruses. Some of the identified
modules combine highly diverse viruses infecting bacteria, archaea, and
eukaryotes, in support of previous hypotheses on direct evolutionary
relationships between viruses from the three domains of cellular life. We
formally identify a set of 14 viral hallmark genes that hold together the genomic
network.
PMID- 27486194
TI - Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene
Dosing and Drug Affinity Responsive Target Stability Screening.
AB - Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half
a million cases of meningitis globally, especially in immunocompromised
individuals. Common fungistatic drugs, such as fluconazole, are less toxic for
patients but have low efficacy for initial therapy of the disease. Effective
therapy against the disease is provided by the fungicidal drug amphotericin B;
however, due to its high toxicity and the difficulty in administering its
intravenous formulation, it is imperative to find new therapies targeting the
fungus. The antiparasitic drug bithionol has been recently identified as having
potent fungicidal activity. In this study, we used a combined gene dosing and
drug affinity responsive target stability (GD-DARTS) screen as well as protein
modeling to identify a common drug binding site of bithionol within multiple NAD
dependent dehydrogenase drug targets. This combination genetic and proteomic
method thus provides a powerful method for identifying novel fungicidal drug
targets for further development. IMPORTANCE: Cryptococcosis is a neglected fungal
meningitis that causes approximately half a million deaths annually. The most
effective antifungal agent, amphotericin B, was developed in the 1950s, and no
effective medicine has been developed for this disease since that time. A key
aspect of amphotericin B's effectiveness is thought to be because of its ability
to kill the fungus (fungicidal activity), rather than just stop or slow its
growth. The present study utilized a recently identified fungicidal agent,
bithionol, to identify potential fungicidal drug targets that can be used in
developing modern fungicidal agents. A combined protein and genetic analysis
approach was used to identify a class of enzymes, dehydrogenases, that the fungus
uses to maintain homeostasis with regard to sugar nutrients. Similarities in the
drug target site were found that resulted in simultaneous inhibition and killing
of the fungus by bithionol. These studies thus identify a common, multitarget
site for antifungal development.
PMID- 27486195
TI - A LuxR Homolog in a Cottonwood Tree Endophyte That Activates Gene Expression in
Response to a Plant Signal or Specific Peptides.
AB - Homologs of the LuxR acyl-homoserine lactone (AHL) quorum-sensing signal receptor
are prevalent in Proteobacteria isolated from roots of the Eastern cottonwood
tree, Populus deltoides Many of these isolates possess an orphan LuxR homolog,
closely related to OryR from the rice pathogen Xanthomonas oryzae OryR does not
respond to AHL signals but, instead, responds to an unknown plant compound. We
discovered an OryR homolog, PipR, in the cottonwood endophyte Pseudomonas sp.
strain GM79. The genes adjacent to pipR encode a predicted ATP-binding cassette
(ABC) peptide transporter and peptidases. We purified the putative peptidases,
PipA and AapA, and confirmed their predicted activities. A transcriptional pipA
gfp reporter was responsive to PipR in the presence of plant leaf macerates, but
it was not influenced by AHLs, similar to findings with OryR. We found that PipR
also responded to protein hydrolysates to activate pipA-gfp expression. Among
many peptides tested, the tripeptide Ser-His-Ser showed inducer activity but at
relatively high concentrations. An ABC peptide transporter mutant failed to
respond to leaf macerates, peptone, or Ser-His-Ser, while peptidase mutants
expressed higher-than-wild-type levels of pipA-gfp in response to any of these
signals. Our studies are consistent with a model where active transport of a
peptidelike signal is required for the signal to interact with PipR, which then
activates peptidase gene expression. The identification of a peptide ligand for
PipR sets the stage to identify plant-derived signals for the OryR family of
orphan LuxR proteins. IMPORTANCE: We describe the transcription factor PipR from
a Pseudomonas strain isolated as a cottonwood tree endophyte. PipR is a member of
the LuxR family of transcriptional factors. LuxR family members are generally
thought of as quorum-sensing signal receptors, but PipR is one of an emerging
subfamily of LuxR family members that respond to compounds produced by plants. We
found that PipR responds to a peptidelike compound, and we present a model for
Pip system signal transduction. A better understanding of plant-responsive LuxR
homologs and the compounds to which they respond is of general importance, as
they occur in dozens of bacterial species that are associated with economically
important plants and, as we report here, they also occur in members of certain
root endophyte communities.
PMID- 27486196
TI - Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination.
AB - Obesity is a risk factor for developing severe influenza virus infection, making
vaccination of utmost importance for this high-risk population. However,
vaccinated obese animals and adults have decreased neutralizing antibody
responses. In these studies, we tested the hypothesis that the addition of either
alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve
neutralizing antibody responses and protect obese mice from challenge. Our
studies demonstrate that adjuvanted vaccine does increase both neutralizing and
nonneutralizing antibody levels compared to vaccine alone. Although obese mice
mount significantly decreased virus-specific antibody responses, both the breadth
and the magnitude of the responses against hemagglutinin (HA) and neuraminidase
(NA) are decreased compared to the responses in lean mice. Importantly, even with
a greater than fourfold increase in neutralizing antibody levels, obese mice are
not protected against influenza virus challenge and viral loads remain elevated
in the respiratory tract. Increasing the antigen dose affords no added
protection, and a decreasing viral dose did not fully mitigate the increased
mortality seen in obese mice. Overall, these studies highlight that, while the
use of an adjuvant does improve seroconversion, vaccination does not fully
protect obese mice from influenza virus challenge, possibly due to the increased
sensitivity of obese animals to infection. Given the continued increase in the
global obesity epidemic, our findings have important implications for public
health. IMPORTANCE: Vaccination is the most effective strategy for preventing
influenza virus infection and is a key component for pandemic preparedness.
However, vaccines may fail to provide optimal protection in high-risk groups,
including overweight and obese individuals. Given the worldwide obesity epidemic,
it is imperative that we understand and improve vaccine efficacy. No work to date
has investigated whether adjuvants increase the protective capacity of influenza
vaccines in the obese host. In these studies, we show that adjuvants increased
the neutralizing and nonneutralizing antibody responses during vaccination of
lean and obese mice to levels considered "protective," and yet, obese mice still
succumbed to infection. This vulnerability is likely due to a combination of
factors, including the increased susceptibility of obese animals to develop
severe and even lethal disease when infected with very low viral titers. Our
studies highlight the critical public health need to translate these findings and
better understand vaccination in this increasing population.
PMID- 27486197
TI - Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs
Required for Host Cell Colonization.
AB - Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia,
affecting infants and adults worldwide. N. meningitidis is also a common
inhabitant of the human nasopharynx and, as such, is highly adapted to its niche.
During bacteremia, N. meningitidis gains access to the blood compartment, where
it adheres to endothelial cells of blood vessels and causes dramatic vascular
damage. Colonization of the nasopharyngeal niche and communication with the
different human cell types is a major issue of the N. meningitidis life cycle
that is poorly understood. Here, highly saturated random transposon insertion
libraries of N. meningitidis were engineered, and the fitness of mutations during
routine growth and that of colonization of endothelial and epithelial cells in a
flow device were assessed in a transposon insertion site sequencing (Tn-seq)
analysis. This allowed the identification of genes essential for bacterial growth
and genes specifically required for host cell colonization. In addition, after
having identified the small noncoding RNAs (sRNAs) located in intergenic regions,
the phenotypes associated with mutations in those sRNAs were defined. A total of
383 genes and 8 intergenic regions containing sRNA candidates were identified to
be essential for growth, while 288 genes and 33 intergenic regions containing
sRNA candidates were found to be specifically required for host cell
colonization. IMPORTANCE: Meningococcal meningitis is a common cause of
meningitis in infants and adults. Neisseria meningitidis (meningococcus) is also
a commensal bacterium of the nasopharynx and is carried by 3 to 30% of healthy
humans. Under some unknown circumstances, N. meningitidis is able to invade the
bloodstream and cause either meningitis or a fatal septicemia known as purpura
fulminans. The onset of symptoms is sudden, and death can follow within hours.
Although many meningococcal virulence factors have been identified, the
mechanisms that allow the bacterium to switch from the commensal to pathogen
state remain unknown. Therefore, we used a Tn-seq strategy coupled to high
throughput DNA sequencing technologies to find genes for proteins used by N.
meningitidis to specifically colonize epithelial cells and primary brain
endothelial cells. We identified 383 genes and 8 intergenic regions containing
sRNAs essential for growth and 288 genes and 33 intergenic regions containing
sRNAs required specifically for host cell colonization.
PMID- 27486198
TI - A culturally tailored Internet cancer support group for Asian American breast
cancer survivors: A randomized controlled pilot intervention study.
AB - Introduction The necessity of culturally competent Internet Cancer Support Groups
(ICSGs) for ethnic minorities has recently been highlighted in order to increase
its attractiveness and usage. The purpose of this study was to determine the
preliminary efficacy of a culturally tailored registered-nurse-moderated ICSG for
Asian American breast cancer survivors in enhancing the women's breast cancer
survivorship experience. Methods The study included two phases: (a) a usability
test and an expert review; and (b) a randomized controlled pilot intervention
study. The usability test was conducted among five Asian American breast cancer
survivors using a one-month online forum, and the expert review was conducted
among five experts using the Cognitive Walkthrough method. The randomized
controlled pilot intervention study (a pre-test and post-test design) was
conducted among 65 Asian American breast cancer survivors. The data were analysed
using content analysis and descriptive and inferential statistics including the
repeated ANOVA. Results All users and experts positively evaluated the program
and provided their suggestions for the display, educational contents, and user
friendly structure. There were significant positive changes in the support care
needs and physical and psychological symptoms ( p < 0.05) of the control group.
There were significant negative changes in the uncertainty level of the
intervention group ( p < 0.10). Controlling for background and disease factors,
the intervention group showed significantly greater improvements than the control
group in physical and psychological symptoms and quality of life ( p < 0.10).
Discussion The findings supported the positive effects of ICSGs on support care
needs, psychological and physical symptoms, and quality of life.
PMID- 27486200
TI - Ionophore Antibiotics as Cancer Stem Cell-Selective Drugs: Open Questions.
PMID- 27486199
TI - Phosphoproteomics to Characterize Host Response During Influenza A Virus
Infection of Human Macrophages.
AB - Influenza A viruses cause infections in the human respiratory tract and give rise
to annual seasonal outbreaks, as well as more rarely dreaded pandemics. Influenza
A viruses become quickly resistant to the virus-directed antiviral treatments,
which are the current main treatment options. A promising alternative approach is
to target host cell factors that are exploited by influenza viruses. To this end,
we characterized the phosphoproteome of influenza A virus infected primary human
macrophages to elucidate the intracellular signaling pathways and critical host
factors activated upon influenza infection. We identified 1675 phosphoproteins,
4004 phosphopeptides and 4146 nonredundant phosphosites. The phosphorylation of
1113 proteins (66%) was regulated upon infection, highlighting the importance of
such global phosphoproteomic profiling in primary cells. Notably, 285 of the
identified phosphorylation sites have not been previously described in publicly
available phosphorylation databases, despite many published large-scale
phosphoproteome studies using human and mouse cell lines. Systematic
bioinformatics analysis of the phosphoproteome data indicated that the
phosphorylation of proteins involved in the ubiquitin/proteasome pathway (such as
TRIM22 and TRIM25) and antiviral responses (such as MAVS) changed in infected
macrophages. Proteins known to play roles in small GTPase-, mitogen-activated
protein kinase-, and cyclin-dependent kinase- signaling were also regulated by
phosphorylation upon infection. In particular, the influenza infection had a
major influence on the phosphorylation profiles of a large number of cyclin
dependent kinase substrates. Functional studies using cyclin-dependent kinase
inhibitors showed that the cyclin-dependent kinase activity is required for
efficient viral replication and for activation of the host antiviral responses.
In addition, we show that cyclin-dependent kinase inhibitors protect IAV-infected
mice from death. In conclusion, we provide the first comprehensive
phosphoproteome characterization of influenza A virus infection in primary human
macrophages, and provide evidence that cyclin-dependent kinases represent
potential therapeutic targets for more effective treatment of influenza
infections.
PMID- 27486201
TI - Long-Term Responders After Brentuximab Vedotin: Single-Center Experience on
Relapsed and Refractory Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma
Patients.
AB - BACKGROUND: Brentuximab vedotin (BV) has shown high overall response rate in
refractory/relapsed Hodgkin lymphoma (HL) and systemic anaplastic large cell
lymphoma (sALCL) with reported long-term response duration in clinical trials,
but few data are available regarding its role in long-term outcomes in real life.
PATIENTS AND METHODS: A single-center observational study was conducted on
patients treated with BV in daily clinical practice to evaluate the long-term
effectiveness of BV in HL and sALCL patients and to check whether clinical trial
results are confirmed in a real-life context. RESULTS: The best response rate in
the treated 53 patients (43 HL and 10 sALCL) was 69.8% (with 46.5% complete
response [CR]) in HL and 100% (80% CR) for sALCL, respectively. With a median
patient follow-up of 36.8 months, the estimated median duration of response was
31.5 months for HL and 17.8 for sALCL, respectively. At the latest available
follow-up, 75% of patients were still in response, with 43% without any
consolidation. Toxicity was primarily neurological and it was rarely so serious
to require dose reduction or interruption. In addition, it always reversed
completely after the end of treatment. CONCLUSION: Our data showed that 51% of
patients treated with BV can be regarded as "long-term responders." Among these
cases, for all patients who underwent stem cell transplantation immediately after
BV, the procedure was consolidative. For patients who have remained in continuous
CR without any consolidation after therapy, BV can induce prolonged disease
control. IMPLICATIONS FOR PRACTICE: Brentuximab vedotin (BV) has shown a high
overall response rate in refractory/relapsed Hodgkin lymphoma and systemic
anaplastic large cell lymphoma, with reported long-term response duration in
clinical trials, whereas few data are available regarding its role in long-term
outcomes in real life. The data reported in this study suggest that BV can induce
the same results in daily clinical practice. The data showed that 51% of patients
treated with BV can be regarded as "long-term responders." Among these cases, BV
can induce prolonged disease control in patients who have remained in continuous
complete response without any consolidation after the drug.
PMID- 27486202
TI - Is Salvage Liver Resection Necessary for Initially Unresectable Hepatocellular
Carcinoma Patients Downstaged by Transarterial Chemoembolization? Ten Years of
Experience.
AB - INTRODUCTION: This study evaluated long-term outcomes of salvage surgery as
additional therapy following downstaging of hepatocellular carcinoma (HCC) with
transarterial chemoembolization (TACE) in patients with initially unresectable
HCC. METHODS: A retrospective analysis was performed of 831 consecutive patients
with unresectable HCC who underwent TACE as initial treatment between June 2004
and December 2014. Of these, 82 patients with downstaged resectable HCC were
enrolled in this study: 43 received salvage surgery (S group) and the remaining
39, who refused salvage resection, were the control group (T group). The primary
endpoint was overall survival (OS). RESULTS: The median OS in the S and T groups
was 49 and 31 months, respectively (p = .027). The 2-, 4-, and 5-year survival
rates were 93%, 47%, and 26% in the S group and 74%, 18%, and 10% in the T group,
respectively (p = .019). Treatment modality (hazard ratio [HR], 0.337; 95%
confidential interval [CI], 0.184-0.616; p < .001) and response to TACE (complete
vs. partial; HR, 3.154; 95% CI, 1.709-5.822; p < .001) were independent
prognostic factors for survival. The median OS for patients in the complete
response and partial response (PR) subgroups was 50 and 49 months, respectively,
in the S group and 54 and 24 months, respectively, in the T group (p = .699 and p
< .001, respectively). The median OS for HCC patients with macroscopic vascular
invasion (MVI) was 58 and 30 months in the S and T groups, respectively (p =
.024). CONCLUSION: Salvage surgery after downstaging of unresectable HCC had a
survival benefit only for patients with MVI or a PR to TACE. IMPLICATIONS FOR
PRACTICE: The results of this study suggest that salvage liver resection after
downstaging of unresectable hepatocellular carcinoma in patients with a complete
response to transarterial chemoembolization (TACE) has a comparable long-term
outcome in this good-prognosis group. Salvage liver resection may provide a
better long-term outcome compared with TACE alone, but only in patients with
macroscopic vascular invasion or those with a partial response to TACE.
PMID- 27486203
TI - Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With
>=3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an
Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD.
AB - BACKGROUND: This retrospective study evaluated the treatment patterns in and
overall survival (OS) of multiple myeloma (MM) patients who were refractory to a
proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) or who had received
three or more prior lines of therapy (LOTs) including a PI and an IMiD. METHODS:
Electronic health records in the IMS LifeLink and OPTUM databases were screened
for indexing periods of 2000-2014 and 2007-2014, respectively. Patients who were
refractory to both a PI and an IMiD (criterion 1) or who received three or more
prior LOTs (including a PI and an IMiD) and showed disease progression within 60
days of their most recent regimen (criterion 2) comprised the eligible
population. Median OS from time of last LOT was assessed for the full cohort,
cohorts meeting criteria 1 and 2, and clinically important subgroups. RESULTS: Of
3,929 and 3,837 patients with MM diagnoses evaluated in the IMS LifeLink and
OPTUM databases, 500 and 162 met the eligibility criteria, respectively. Similar
median OS was observed for eligible patients in the IMS LifeLink and OPTUM
databases (7.9 vs. 7.9 months; p = .5358). In subgroup analyses of the IMS
LifeLink data set, median OS was longer in patients <65 years of age than it was
for those >=65 years at eligibility (9.5 vs 6.7 months; p < .01) and in patients
with good or unreported versus poor performance status at last claim (7.8 or 8.8
vs. 2.9 months; p < .0001). CONCLUSION: The findings of this survival analysis
suggest that outcomes for these patients remain poor despite the availability of
newer agents. IMPLICATIONS FOR PRACTICE: This real-world retrospective study of
electronic health records examines the survival outcomes of patients with
multiple myeloma who are heavily pretreated or highly refractory to currently
approved treatments, including recently approved proteasome inhibitors and
immunomodulatory drugs. This survival analysis showed that outcomes for these
patients remain poor despite the availability of newer agents, with median
overall survival of approximately 8 months. These findings highlight a critical
need to develop novel therapies for these patients and also serve as a reference
point against which emerging agents for heavily pretreated or highly refractory
disease may be evaluated.
PMID- 27486206
TI - Time enough for tears?
PMID- 27486204
TI - Randomised, double-blind, placebo-controlled trial with azithromycin selects for
anti-inflammatory microbial metabolites in the emphysematous lung.
AB - INTRODUCTION: Azithromycin (AZM) reduces pulmonary inflammation and exacerbations
in patients with COPD having emphysema. The antimicrobial effects of AZM on the
lower airway microbiome are not known and may contribute to its beneficial
effects. Here we tested whether AZM treatment affects the lung microbiome and
bacterial metabolites that might contribute to changes in levels of inflammatory
cytokines in the airways. METHODS: 20 smokers (current or ex-smokers) with
emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks.
Bronchoalveolar lavage (BAL) was performed at baseline and after treatment.
Measurements performed in acellular BAL fluid included 16S rRNA gene sequences
and quantity; 39 cytokines, chemokines and growth factors and 119 identified
metabolites. The response to lipopolysaccharide (LPS) by alveolar macrophages
after ex-vivo treatment with AZM or bacterial metabolites was assessed. RESULTS:
Compared with placebo, AZM did not alter bacterial burden but reduced alpha
diversity, decreasing 11 low abundance taxa, none of which are classical
pulmonary pathogens. Compared with placebo, AZM treatment led to reduced in-vivo
levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-alpha,
interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites
including glycolic acid, indol-3-acetate and linoleic acid. Glycolic acid and
indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage
generation of CXCL1, TNF-alpha, IL-13 and IL-12p40. CONCLUSION: AZM treatment
altered both lung microbiota and metabolome, affecting anti-inflammatory
bacterial metabolites that may contribute to its therapeutic effects. TRIAL
REGISTRATION NUMBER: NCT02557958.
PMID- 27486205
TI - Individualized prediction of lung-function decline in chronic obstructive
pulmonary disease.
AB - BACKGROUND: The rate of lung-function decline in chronic obstructive pulmonary
disease (COPD) varies substantially among individuals. We sought to develop and
validate an individualized prediction model for forced expiratory volume at 1
second (FEV1) in current smokers with mild-to-moderate COPD. METHODS: Using data
from a large long-term clinical trial (the Lung Health Study), we derived mixed
effects regression models to predict future FEV1 values over 11 years according
to clinical traits. We modelled heterogeneity by allowing regression coefficients
to vary across individuals. Two independent cohorts with COPD were used for
validating the equations. RESULTS: We used data from 5594 patients (mean age 48.4
yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction
equations. There was significant between-individual variability in the rate of
FEV1 decline, with the interval for the annual rate of decline that contained 95%
of individuals being -124 to -15 mL/yr for smokers and -83 to 15 mL/yr for
sustained quitters. Clinical variables in the final model explained 88% of
variation around follow-up FEV1. The C statistic for predicting severity grades
was 0.90. Prediction equations performed robustly in the 2 external data sets.
INTERPRETATION: A substantial part of individual variation in FEV1 decline can be
explained by easily measured clinical variables. The model developed in this work
can be used for prediction of future lung health in patients with mild-to
moderate COPD. TRIAL REGISTRATION: Lung Health Study - ClinicalTrials.gov, no.
NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study -
ClinicalTrials.gov, no. NCT00751660.
PMID- 27486207
TI - Kounis syndrome and systemic mastocytosis in a 52-year-old man having surgery.
PMID- 27486208
TI - Metastatic pulmonary calcification in end-stage renal failure.
PMID- 27486210
TI - Older doctors under increasing regulatory scrutiny.
PMID- 27486209
TI - Inuit suicide prevention strategy strives to save lives.
PMID- 27486211
TI - Infoway calls for e-prescribing proposals.
PMID- 27486212
TI - Predicting individual lung-function trajectories: An opportunity for prevention?
PMID- 27486213
TI - (1,3) beta-D-Glucan in Bronchoalveolar Lavage of Lung Transplant Recipients for
the Diagnosis of Invasive Pulmonary Aspergillosis.
AB - (1,3) beta-D-Glucan (BDG) is present in the cell wall of most fungi. Its
detection in serum has been useful in the diagnosis of invasive aspergillosis
(IA) in patients with hematologic malignancies. However, assaying for BDG did not
perform well in the serum of lung transplant recipients. We undertook to study
the performance of BDG in the bronchoalveolar lavage (BAL) of lung transplant
recipients for the diagnosis of invasive pulmonary aspergillosis (IPA). Available
and stored BAL samples from lung transplant recipients at the Toronto General
Hospital between October 2007 and April 2013 were tested for BDG using the
Fungitell kit from the Associates of Cape Cod Inc, Falmouth, MA, USA : The
International Society for Heart and Lung transplantation (ISHLT) criteria was
used for the diagnosis of IA. Of 195 samples, there were ten episodes of IA. The
sensitivity and specificity of the test were 80% and 53% and 60% and 70% at 41
pg/ml and 108 pg/ml cut-offs, respectively. On excluding 52 bronchoscopies due to
receipt of anti-Aspergillus therapy during specimen collection, the sensitivity
and specificity improved to 75% and 91%, respectively, at a 524 pg/ml cut-off.
However, only four episodes of IA remained in this analysis. Using BDG in BAL of
lung transplant recipients for the diagnosis of IA, our study demonstrated
moderate sensitivity and specificity.
PMID- 27486214
TI - Trichophyton erinacei in pet hedgehogs in Spain: Occurrence and revision of its
taxonomic status.
AB - Hedgehogs have increased in popularity as pets in Spain but there are no data of
infection rates of this exotic animal with dermatophytes in our country. During
the period of 2008-2011 a total of 20 pet hedgehogs (19 African pygmy hedgehogs
and 1 Egyptian long-eared hedgehog) suspected of having dermatophytoses were
studied. This is the first survey of the occurrence of T. erinacei in household
hedgehogs in Spain. The T. erinacei infection rate was 50% (9 out of 19 African
pygmy hedgehogs, and the one Egyptian long-eared hedgehog surveyed).
Morphological identification of the isolates was confirmed by molecular analysis.
All the strains had the same ITS sequence and showed 100% sequence similarity to
T. erinacei type strain CBS 511.73 (AB 105793). The Spanish isolates were
confirmed as T. erinacei urease positive. On the basis of ITS sequences, T.
erinacei is a species close to but separate from the taxa included in the A.
benhamiae complex. Review of the current literature on DNA-based methods for
identification of species included in this complex has highlighted the urgent
need to reach a consensus in species circumscription and classification system
accepted by all mycologists.
PMID- 27486215
TI - A subdose of fluconazole alters the virulence of Cryptococcus gattii during
murine cryptococcosis and modulates type I interferon expression.
AB - Cryptococcosis is an invasive infection caused by yeast-like fungus of the genera
Cryptococcus spp. The antifungal therapy for this disease provides some toxicity
and the incidence of infections caused by resistant strains increased. Thus, we
aimed to assess the consequences of fluconazole subdoses during the treatment of
cryptococcosis in the murine inflammatory response and in the virulence factors
of Cryptococcus gattii. Mice infected with Cryptococcus gattii were treated with
subdoses of fluconazole. We determined the behavior of mice and type 1 interferon
expression during the treatment; we also studied the virulence factors and
susceptibility to fluconazole for the colonies recovered from the animals. A
subdose of fluconazole prolonged the survival of mice, but the morbidity of
cryptococcosis was higher in treated animals. These data were linked to the
increase in: (i) fluconazole minimum inhibitory concentration, (ii) capsule size
and (iii) melanization of C. gattii, which probably led to the increased
expression of type I interferons in the brains of mice but not in the lungs. In
conclusion, a subdose of fluconazole altered fungal virulence factors and
susceptibility to this azole, leading to an altered inflammatory host response
and increased morbidity.
PMID- 27486216
TI - Quantification of A. fumigatus-specific CD154+ T-cells-preanalytic
considerations.
AB - Fungal specific CD154+ T-cells have been described as a biomarker in invasive
aspergillosis. The influence of sample storage on the detection of these cells
was assessed. Six-hour delay prior to PBMC isolation is associated with an 18%
decrease of cell viability and alterations of the cellular composition of the
sample. This results in 87% reduction of CD154+ A. fumigatus specific cells due
to reduced assay sensitivity and increased background values in unstimulated
samples. If prompt cell measurement is not feasible, isolated PBMCs can be frozen
(at -20 degrees C and -80 degrees C) and processed later with comparable assay
reliability (mean value fresh vs. thawing: 0.126, 0.133; Pearson-Coefficient:
0.962).
PMID- 27486217
TI - Stories of MDM: It Only Takes One.
PMID- 27486218
TI - Development of a Conceptual Model of Disease Progression for Use in Economic
Modeling of Chronic Obstructive Pulmonary Disease.
AB - BACKGROUND: To develop and validate a new conceptual model (CM) of chronic
obstructive pulmonary disease (COPD) for use in disease progression and economic
modeling. The CM identifies and describes qualitative associations between
disease attributes, progression and outcomes. METHODS: A literature review was
performed to identify any published CMs or literature reporting the impact and
association of COPD disease attributes with outcomes. After critical analysis of
the literature, a Steering Group of experts from the disciplines of health
economics, epidemiology and clinical medicine was convened to develop a draft CM,
which was refined using a Delphi process. The refined CM was validated by testing
for associations between attributes using data from the Evaluation of COPD
Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). RESULTS:
Disease progression attributes included in the final CM were history and
occurrence of exacerbations, lung function, exercise capacity, signs and symptoms
(cough, sputum, dyspnea), cardiovascular disease comorbidities, 'other'
comorbidities (including depression), body composition (body mass index),
fibrinogen as a biomarker, smoking and demographic characteristics (age, gender).
Mortality and health-related quality of life were determined to be the most
relevant final outcome measures for this model, intended to be the foundation of
an economic model of COPD. CONCLUSION: The CM is being used as the foundation for
developing a new COPD model of disease progression and to provide a framework for
the analysis of patient-level data. The CM is available as a reference for the
implementation of further disease progression and economic models.
PMID- 27486219
TI - Does robot-assisted gait training improve ambulation in highly disabled multiple
sclerosis people? A pilot randomized control trial.
AB - BACKGROUND: Robotic training is commonly used to assist walking training in
patients affected by multiple sclerosis (MS) with non-conclusive results.
OBJECTIVE: To compare the effect of robot-assisted gait training (RAGT) with that
of conventional walking training (CWT) on gait competencies, global ability,
fatigue and spasticity in a group of severely affected patients with MS. METHODS:
A pilot, single-blind randomized controlled trial was conducted in 43 severe
(Expanded Disability Status Scale (EDSS) score of 6-7.5) and non-autonomous
ambulant in-patients with MS. Experimental group performed 12 sessions of RAGT,
whereas control group performed the same amount of CWT. Primary outcome measures
were gait ability assessed by 2 minutes walking test and Functional Ambulatory
Category; secondary outcomes were global ability (modified Barthel Index), global
mobility (Rivermead Mobility Index), severity of disease (EDSS) and subjectively
perceived fatigue (Fatigue Severity Scale). RESULTS: The number of subjects who
achieved a clinical significant improvement was significantly higher in RAGT than
in CWT ( p < 0.05 for both primary outcome measures). RAGT also led to an
improvement in all the other clinical parameters (global ability: p < 0.001,
global mobility: p < 0.001, EDSS: p = 0.014 and fatigue: p = 0.001). CONCLUSIONS:
RAGT improved the walking competencies in non-autonomous ambulant patients with
MS, with benefits in terms of perceived fatigue.
PMID- 27486220
TI - Is Mutation Random or Targeted?: No Evidence for Hypermutability in Snail Toxin
Genes.
AB - Ever since Luria and Delbruck, the notion that mutation is random with respect to
fitness has been foundational to modern biology. However, various studies have
claimed striking exceptions to this rule. One influential case involves toxin
encoding genes in snails of the genus Conus, termed conotoxins, a large gene
family that undergoes rapid diversification of their protein-coding sequences by
positive selection. Previous reconstructions of the sequence evolution of
conotoxin genes claimed striking patterns: (1) elevated synonymous change,
interpreted as being due to targeted "hypermutation" in this region; (2) elevated
transversion-to-transition ratios, interpreted as reflective of the particular
mechanism of hypermutation; and (3) much lower rates of synonymous change in the
codons encoding several highly conserved cysteine residues, interpreted as strong
position-specific codon bias. This work has spawned a variety of studies on the
potential mechanisms of hypermutation and on causes for cysteine codon bias, and
has inspired hypermutation hypotheses for various other fast-evolving genes.
Here, I show that all three findings are likely to be artifacts of statistical
reconstruction. First, by simulating nonsynonymous change I show that high rates
of dN can lead to overestimation of dS. Second, I show that there is no evidence
for any of these three patterns in comparisons of closely related conotoxin
sequences, suggesting that the reported findings are due to breakdown of
statistical methods at high levels of sequence divergence. The current findings
suggest that mutation and codon bias in conotoxin genes may not be atypical, and
that random mutation and selection can explain the evolution of even these
exceptional loci.
PMID- 27486221
TI - PoPoolationTE2: Comparative Population Genomics of Transposable Elements Using
Pool-Seq.
AB - The evolutionary dynamics of transposable elements (TEs) are still poorly
understood. One reason is that TE abundance needs to be studied at the population
level, but sequencing individuals on a population scale is still too expensive to
characterize TE abundance in multiple populations. Although sequencing pools of
individuals dramatically reduces sequencing costs, a comparison of TE abundance
between pooled samples has been difficult, if not impossible, due to various
biases. Here, we introduce a novel bioinformatic tool, PoPoolationTE2, which is
specifically tailored for the comparison of TE abundance among pooled population
samples or different tissues. Using computer simulations, we demonstrate that
PoPoolationTE2 not only faithfully recovers TE insertion frequencies and
positions but, by homogenizing the power to identify TEs across samples, it
provides an unbiased comparison of TE abundance between pooled population
samples. We anticipate that PoPoolationTE2 will greatly facilitate the analysis
of TE insertion patterns in a broad range of applications.
PMID- 27486222
TI - Smoothed Bootstrap Aggregation for Assessing Selection Pressure at Amino Acid
Sites.
AB - To detect positive selection at individual amino acid sites, most methods use an
empirical Bayes approach. After parameters of a Markov process of codon evolution
are estimated via maximum likelihood, they are passed to Bayes formula to compute
the posterior probability that a site evolved under positive selection. A
difficulty with this approach is that parameter estimates with large errors can
negatively impact Bayesian classification. By assigning priors to some
parameters, Bayes Empirical Bayes (BEB) mitigates this problem. However, as
implemented, it imposes uniform priors, which causes it to be overly conservative
in some cases. When standard regularity conditions are not met and parameter
estimates are unstable, inference, even under BEB, can be negatively impacted. We
present an alternative to BEB called smoothed bootstrap aggregation (SBA), which
bootstraps site patterns from an alignment of protein coding DNA sequences to
accommodate the uncertainty in the parameter estimates. We show that deriving the
correction for parameter uncertainty from the data in hand, in combination with
kernel smoothing techniques, improves site specific inference of positive
selection. We compare BEB to SBA by simulation and real data analysis. Simulation
results show that SBA balances accuracy and power at least as well as BEB, and
when parameter estimates are unstable, the performance gap between BEB and SBA
can widen in favor of SBA. SBA is applicable to a wide variety of other inference
problems in molecular evolution.
PMID- 27486223
TI - Divergent Ah Receptor Ligand Selectivity during Hominin Evolution.
AB - We have identified a fixed nonsynonymous sequence difference between humans
(Val381; derived variant) and Neandertals (Ala381; ancestral variant) in the
ligand-binding domain of the aryl hydrocarbon receptor (AHR) gene. In an exome
sequence analysis of four Neandertal and Denisovan individuals compared with nine
modern humans, there are only 90 total nucleotide sites genome-wide for which
archaic hominins are fixed for the ancestral nonsynonymous variant and the modern
humans are fixed for the derived variant. Of those sites, only 27, including
Val381 in the AHR, also have no reported variability in the human dbSNP database,
further suggesting that this highly conserved functional variant is a rare event.
Functional analysis of the amino acid variant Ala381 within the AHR carried by
Neandertals and nonhuman primates indicate enhanced polycyclic aromatic
hydrocarbon (PAH) binding, DNA binding capacity, and AHR mediated transcriptional
activity compared with the human AHR. Also relative to human AHR, the Neandertal
AHR exhibited 150-1000 times greater sensitivity to induction of Cyp1a1 and
Cyp1b1 expression by PAHs (e.g., benzo(a)pyrene). The resulting CYP1A1/CYP1B1
enzymes are responsible for PAH first pass metabolism, which can result in the
generation of toxic intermediates and perhaps AHR-associated toxicities. In
contrast, the human AHR retains the ancestral sensitivity observed in primates to
nontoxic endogenous AHR ligands (e.g., indole, indoxyl sulfate). Our findings
reveal that a functionally significant change in the AHR occurred uniquely in
humans, relative to other primates, that would attenuate the response to many
environmental pollutants, including chemicals present in smoke from fire use
during cooking.
PMID- 27486224
TI - Development and Application of a Novel Model System to Study "Active" and
"Passive" Tumor Targeting.
AB - Macromolecular reagents can be targeted to tumors through active and passive
mechanisms. "Active" targeting involves moieties, such as receptor ligands, to
direct tumor cell binding, whereas "passive" targeting relies on long reagent
circulating half-life, abnormal tumor vasculature, and poor lymphatic drainage
for tumor entrapment. Here, we sought to study the impact of reagent circulating
half-life on "active" and "passive" tumor uptake. The humanized prostate-specific
membrane antigen (PSMA)-targeting antibody HuJ591 was used as the "active"
targeting agent. HuJ591 was labeled with a Near Infrared (NIR) dye and its
circulating half-life was modified by conjugation to high-molecular-weight
Polyethylene Glycol (PEG). PEGylation did not negatively impact PSMA-binding
specificity. "Active" and "passive" tumor targeting of intravenously injected
antibody conjugates were then quantified by NIR fluorescent imaging of
immunocompromised mice bearing bilateral isogenic PSMA-positive and PSMA-negative
human tumor xenografts. Two isogenic tumor pairs were applied, PC3 +/- PSMA (PC3
PIP/PC3-Flu) or LMD-MDA-MB-231 +/- PSMA (LMD-PSMA/LMD). This study provided a
unique model system to simultaneously observe "active" and "passive" tumor
targeting within a single animal. "Passive" targeting was observed in all PSMA
negative tumors, and was not enhanced by increased HuJ591 size or extended
circulating half-life. Interestingly, "active" targeting was only successful in
some situations. Both PSMA-positive tumor models could be actively targeted with
J591-IR800 and J591-PEG10K. However, the larger J591-PEG30K enhanced "active"
targeting in the PC-3 tumor models, but inhibited "active" targeting the LMD-MDA
MB-231 tumor model. Successful "active" targeting was associated with higher PSMA
expression. These results support the potential for "active" targeting to enhance
overall macromolecular reagent uptake within tumors. Mol Cancer Ther; 15(10);
2541-50. (c)2016 AACR.
PMID- 27486225
TI - A Novel Small Molecule Activator of Nuclear Receptor SHP Inhibits HCC Cell
Migration via Suppressing Ccl2.
AB - Small heterodimer partner (SHP, NR0B2) is a nuclear orphan receptor without
endogenous ligands. Due to its crucial inhibitory role in liver cancer, it is of
importance to identify small molecule agonists of SHP. As such, we initiated a
probe discovery effort to identify compounds capable of modulating SHP function.
First, we performed binding assays using small molecule microarrays (SMM) and
discovered 5-(diethylsulfamoyl)-3-hydroxynaphthalene-2-carboxylic acid (DSHN) as
a novel activator of SHP. DSHN transcriptionally activated Shp mRNA, but also
stabilized the SHP protein by preventing its ubiquitination and degradation.
Second, we identified Ccl2 as a new SHP target gene by RNA-seq. We showed that
activation of SHP by DSHN repressed Ccl2 expression and secretion by inhibiting
p65 activation of CCL2 promoter activity, as demonstrated in vivo in Shp-/- mice
and in vitro in HCC cells with SHP overexpression and knockdown. Third, we
elucidated a strong inhibitory effect of SHP and DSHN on HCC cell migration and
invasion by antagonizing the effect of CCL2. Lastly, by interrogating a publicly
available database to retrieve SHP expression profiles from multiple types of
human cancers, we established a negative association of SHP expression with human
cancer metastasis and patient survival. In summary, the discovery of a novel
small molecule activator of SHP provides a therapeutic perspective for future
translational and preclinical studies to inhibit HCC metastasis by blocking Ccl2
signaling. Mol Cancer Ther; 15(10); 2294-301. (c)2016 AACR.
PMID- 27486226
TI - Cardiac Emergency Response Planning for Schools: A Policy Statement.
AB - A sudden cardiac arrest in school or at a school event is potentially devastating
to families and communities. An appropriate response to such an event-as promoted
by developing, implementing, and practicing a cardiac emergency response plan
(CERP)-can increase survival rates. Understanding that a trained lay-responder
team within the school can make a difference in the crucial minutes between the
time when the victim collapses and when emergency medical services arrive
empowers school staff and can save lives. In 2015, the American Heart Association
convened a group of stakeholders to develop tools to assist schools in developing
CERPs. This article reviews the critical components of a CERP and a CERP team,
the factors that should be taken into account when implementing the CERP, and
recommendations for policy makers to support CERPs in schools.
PMID- 27486227
TI - Asthma and Vocal Cord Dysfunction: Can You Tell the Difference?
AB - School nurses care for students with asthma on a daily basis, but what happens
when the asthma medication is administered and symptoms persist? As a part of
care coordination, the school nurse provides ongoing assessment and care for
students with asthma. When symptoms persist despite treatment, school nurses need
to consider other issues such as Vocal Cord Dysfunction (VCD). The purpose of
this article is to highlight the similarities and differences in the
pathophysiology and treatment of both asthma and VCD.
PMID- 27486228
TI - Moving toward Light in Response to a Gas: A Novel Cyanobacterial Ethylene
Receptor.
PMID- 27486229
TI - Size regulation blossoms in Kobe.
AB - Coincident with the blossoming of the sakura was the 14th annual CDB Symposium
hosted by the RIKEN Center for Developmental Biology in Kobe, Japan. This year's
meeting, 'Size in Development: Growth, Shape and Allometry' focused on the
molecular and cellular mechanisms underlying differences in size and shape and
how they have evolved. On display was the power of using diverse approaches
ranging from the study of organoids to whole organisms.
PMID- 27486231
TI - Blood vessel formation and function in bone.
AB - In addition to their conventional role as a conduit system for gases, nutrients,
waste products or cells, blood vessels in the skeletal system play active roles
in controlling multiple aspects of bone formation and provide niches for
hematopoietic stem cells that reside within the bone marrow. In addition, recent
studies have highlighted roles for blood vessels during bone healing. Here, we
provide an overview of the architecture of the bone vasculature and discuss how
blood vessels form within bone, how their formation is modulated, and how they
function during development and fracture repair.
PMID- 27486230
TI - Direct lineage reprogramming via pioneer factors; a detour through developmental
gene regulatory networks.
AB - Although many approaches have been employed to generate defined fate in vitro,
the resultant cells often appear developmentally immature or incompletely
specified, limiting their utility. Growing evidence suggests that current methods
of direct lineage conversion may rely on the transition through a developmental
intermediate. Here, I hypothesize that complete conversion between cell fates is
more probable and feasible via reversion to a developmentally immature state. I
posit that this is due to the role of pioneer transcription factors in engaging
silent, unmarked chromatin and activating hierarchical gene regulatory networks
responsible for embryonic patterning. Understanding these developmental contexts
will be essential for the precise engineering of cell identity.
PMID- 27486234
TI - The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic
Diabetes.
AB - HNF4A mutations cause increased birth weight, transient neonatal hypoglycemia,
and maturity onset diabetes of the young (MODY). The most frequently reported
HNF4A mutation is p.R114W (previously p.R127W), but functional studies have shown
inconsistent results; there is a lack of cosegregation in some pedigrees and an
unexpectedly high frequency in public variant databases. We confirm that p.R114W
is a pathogenic mutation with an odds ratio of 30.4 (95% CI 9.79-125, P = 2 * 10(
21)) for diabetes in our MODY cohort compared with control subjects. p.R114W
heterozygotes did not have the increased birth weight of patients with other
HNF4A mutations (3,476 g vs. 4,147 g, P = 0.0004), and fewer patients responded
to sulfonylurea treatment (48% vs. 73%, P = 0.038). p.R114W has reduced
penetrance; only 54% of heterozygotes developed diabetes by age 30 years compared
with 71% for other HNF4A mutations. We redefine p.R114W as a pathogenic mutation
that causes a distinct clinical subtype of HNF4A MODY with reduced penetrance,
reduced sensitivity to sulfonylurea treatment, and no effect on birth weight.
This has implications for diabetes treatment, management of pregnancy, and
predictive testing of at-risk relatives. The increasing availability of large
scale sequence data is likely to reveal similar examples of rare, low-penetrance
MODY mutations.
PMID- 27486235
TI - Acute Effects of Oral Dehydroepiandrosterone on Counterregulatory Responses
During Repeated Hypoglycemia in Healthy Humans.
AB - We tested the hypothesis that acute administration of oral dehydroepiandrosterone
(DHEA) during episodes of repeated hypoglycemia can prevent the development of
hypoglycemia-associated neuroendocrine and autonomic failure in healthy humans.
Twenty-seven individuals (16 men, 11 women) participated in two separate
randomized, single-blind, 2-day protocols. Day 1 consisted of morning and
afternoon 2-h hypoglycemic clamps (2.9 mmol/L) with 800 mg of DHEA or placebo
administered before each clamp. Day 2 consisted of a single 2-h hypoglycemic
clamp (2.9 mmol/L) following either DHEA (1,600 mg) or placebo. A 3-tritiated
glucose was used to determine glucose kinetics during hypoglycemia on day 2.
Antecedent hypoglycemia with placebo resulted in significant reductions of
epinephrine, norepinephrine, glucagon, growth hormone, cortisol, endogenous
glucose production, and lipolytic and symptom responses. During hypoglycemia on
day 2, DHEA prevented blunting of all neuroendocrine, autonomic nervous system
(ANS), metabolic, and symptom counterregulatory responses following hypoglycemia
on day 1. In summary, DHEA can acutely preserve a wide range of key
neuroendocrine, ANS, and metabolic counterregulatory homeostatic responses during
repeated hypoglycemia. We conclude that DHEA may have acute effects to protect
against hypoglycemia-associated neuroendocrine and autonomic failure in healthy
humans.
PMID- 27486236
TI - Heme-Regulated eIF2alpha Kinase Modulates Hepatic FGF21 and Is Activated by
PPARbeta/delta Deficiency.
AB - Fibroblast growth factor 21 (FGF21), a peptide hormone with pleiotropic effects
on carbohydrate and lipid metabolism, is considered a target for the treatment of
diabetes. We investigated the role of peroxisome proliferator-activated receptor
(PPAR) beta/delta deficiency in hepatic FGF21 regulation. Increased Fgf21
expression was observed in the livers of PPARbeta/delta-null mice and in mouse
primary hepatocytes when this receptor was knocked down by small interfering RNA
(siRNA). Increased Fgf21 was associated with enhanced protein levels in the heme
regulated eukaryotic translation initiation factor 2alpha (eIF2alpha) kinase
(HRI). This increase caused enhanced levels of phosphorylated eIF2alpha and
activating transcription factor (ATF) 4, which is essential for Fgf21-induced
expression. siRNA analysis demonstrated that HRI regulates Fgf21 expression in
primary hepatocytes. Enhanced Fgf21 expression attenuated tunicamycin-induced
endoplasmic reticulum stress, as demonstrated by using a neutralizing antibody
against FGF21. Of note, increased Fgf21 expression in mice fed a high-fat diet or
hepatocytes exposed to palmitate was accompanied by reduced PPARbeta/delta and
activation of the HRI-eIF2alpha-ATF4 pathway. Moreover, pharmacological
activation of HRI increased Fgf21 expression and reduced lipid-induced hepatic
steatosis and glucose intolerance, but these effects were not observed in Fgf21
null mice. Overall, these findings suggest that HRI is a potential target for
regulating hepatic FGF21 levels.
PMID- 27486238
TI - Utilization of Stable Isotope Labeling to Facilitate the Identification of Polar
Metabolites of KAF156, an Antimalarial Agent.
AB - Identification of polar metabolites of drug candidates during development is
often challenging. Several prominent polar metabolites of 2-amino-1-(2-(4
fluorophenyl)-3-((4-fluorophenyl)amino)-8,8-dimethyl-5,6-dihydroimidazo[1,2
a]pyrazin-7(8H)-yl)ethanone ([(14)C]KAF156), an antimalarial agent, were detected
in rat urine from an absorption, distribution, metabolism, and excretion study
but could not be characterized by liquid chromatography-tandem mass spectrometry
(LC-MS/MS) because of low ionization efficiency. In such instances, a strategy
often chosen by investigators is to use a radiolabeled compound with high
specific activity, having an isotopic mass ratio (i.e., [(12)C]/[(14)C]) and mass
difference that serve as the basis for a mass filter using accurate mass
spectrometry. Unfortunately, [(14)C]KAF156-1 was uniformly labeled (n = 1-6) with
the mass ratio of ~0.1. This ratio was insufficient to be useful as a mass filter
despite the high specific activity (120 MUCi/mg). At this stage in development,
stable isotope labeled [(13)C6]KAF156-1 was available as the internal standard
for the quantification of KAF156. We were thus able to design an oral dose as a
mixture of [(14)C]KAF156-1 (specific activity 3.65 MUCi/mg) and [(13)C6]KAF156-1
with a mass ratio of [(12)C]/[(13)C6] as 0.9 and the mass difference as 6.0202.
By using this mass filter strategy, four polar metabolites were successfully
identified in rat urine. Subsequently, using a similar dual labeling approach,
[(14)C]KAF156-2 and [(13)C2]KAF156-2 were synthesized to allow the detection of
any putative polar metabolites that may have lost labeling during
biotransformations using the previous [(14)C]KAF156-1. Three polar metabolites
were thereby identified and M43, a less polar metabolite, was proposed as the key
intermediate metabolite leading to the formation of a total of seven polar
metabolites. Overall this dual labeling approach proved practical and valuable
for the identification of polar metabolites by LC-MS/MS.
PMID- 27486240
TI - News Feature: Prehistoric animals, in living color.
PMID- 27486237
TI - Youth-Onset Type 2 Diabetes Consensus Report: Current Status, Challenges, and
Priorities.
AB - Type 2 diabetes is a significant and increasing burden in adolescents and young
adults. Clear strategies for research, prevention, and treatment of the disease
in these vulnerable patients are needed. Evidence suggests that type 2 diabetes
in children is different not only from type 1 but also from type 2 diabetes in
adults. Understanding the unique pathophysiology of type 2 diabetes in youth, as
well as the risk of complications and the psychosocial impact, will enable
industry, academia, funding agencies, advocacy groups, and regulators to
collectively evaluate both current and future research, treatment, and prevention
approaches. This Consensus Report characterizes type 2 diabetes in children,
evaluates the fundamental differences between childhood and adult disease,
describes the current therapeutic options, and discusses challenges to and
approaches for developing new treatments.
PMID- 27486242
TI - Reply to Marom et al.: Mitochondrial panmixia in dromedaries predates ancient
caravan trading.
PMID- 27486243
TI - Note on the contribution of genetics to understanding the organization of camel
caravans in antiquity.
PMID- 27486244
TI - Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker
proteins.
AB - Dishevelled (DVL) is a key scaffolding protein and a branching point in Wnt
signaling pathways. Here, we present conclusive evidence that DVL regulates the
centrosomal cycle. We demonstrate that DVL dishevelled and axin (DIX) domain, but
not DIX domain-mediated multimerization, is essential for DVL's centrosomal
localization. DVL accumulates during the cell cycle and associates with NIMA
related kinase 2 (NEK2), which is able to phosphorylate DVL at a multitude of
residues, as detected by a set of novel phospho-specific antibodies. This creates
interfaces for efficient binding to CDK5 regulatory subunit-associated protein 2
(CDK5RAP2) and centrosomal Nek2-associated protein 1 (C-NAP1), two proteins of
the centrosomal linker. Displacement of DVL from the centrosome and its release
into the cytoplasm on NEK2 phosphorylation is coupled to the removal of linker
proteins, an event necessary for centrosomal separation and proper formation of
the mitotic spindle. Lack of DVL prevents NEK2-controlled dissolution of loose
centrosomal linker and subsequent centrosomal separation. Increased DVL levels,
in contrast, sequester centrosomal NEK2 and mimic monopolar spindle defects
induced by a dominant negative version of this kinase. Our study thus uncovers
molecular crosstalk between centrosome and Wnt signaling.
PMID- 27486245
TI - Intratumoral oxygen gradients mediate sarcoma cell invasion.
AB - Hypoxia is a critical factor in the progression and metastasis of many cancers,
including soft tissue sarcomas. Frequently, oxygen (O2) gradients develop in
tumors as they grow beyond their vascular supply, leading to heterogeneous areas
of O2 depletion. Here, we report the impact of hypoxic O2 gradients on sarcoma
cell invasion and migration. O2 gradient measurements showed that large sarcoma
mouse tumors (>300 mm(3)) contain a severely hypoxic core [<=0.1% partial
pressure of O2 (pO2)] whereas smaller tumors possessed hypoxic gradients
throughout the tumor mass (0.1-6% pO2). To analyze tumor invasion, we used O2
controllable hydrogels to recreate the physiopathological O2 levels in vitro.
Small tumor grafts encapsulated in the hydrogels revealed increased invasion that
was both faster and extended over a longer distance in the hypoxic hydrogels
compared with nonhypoxic hydrogels. To model the effect of the O2 gradient
accurately, we examined individual sarcoma cells embedded in the O2-controllable
hydrogel. We observed that hypoxic gradients guide sarcoma cell motility and
matrix remodeling through hypoxia-inducible factor-1alpha (HIF-1alpha)
activation. We further found that in the hypoxic gradient, individual cells
migrate more quickly, across longer distances, and in the direction of increasing
O2 tension. Treatment with minoxidil, an inhibitor of hypoxia-induced sarcoma
metastasis, abrogated cell migration and matrix remodeling in the hypoxic
gradient. Overall, we show that O2 acts as a 3D physicotactic agent during
sarcoma tumor invasion and propose the O2-controllable hydrogels as a predictive
system to study early stages of the metastatic process and therapeutic targets.
PMID- 27486246
TI - Spatial organization of bacterial transcription and translation.
AB - In bacteria such as Escherichia coli, DNA is compacted into a nucleoid near the
cell center, whereas ribosomes-molecular complexes that translate mRNAs into
proteins-are mainly localized to the poles. We study the impact of this spatial
organization using a minimal reaction-diffusion model for the cellular
transcriptional-translational machinery. Although genome-wide mRNA-nucleoid
segregation still lacks experimental validation, our model predicts that
[Formula: see text] of mRNAs are segregated to the poles. In addition, our
analysis reveals a "circulation" of ribosomes driven by the flux of mRNAs, from
synthesis in the nucleoid to degradation at the poles. We show that our results
are robust with respect to multiple, biologically relevant factors, such as mRNA
degradation by RNase enzymes, different phases of the cell division cycle and
growth rates, and the existence of nonspecific, transient interactions between
ribosomes and mRNAs. Finally, we confirm that the observed nucleoid size stems
from a balance between the forces that the chromosome and mRNAs exert on each
other. This suggests a potential global feedback circuit in which gene expression
feeds back on itself via nucleoid compaction.
PMID- 27486247
TI - The stringent response regulates adaptation to darkness in the cyanobacterium
Synechococcus elongatus.
AB - The cyanobacterium Synechococcus elongatus relies upon photosynthesis to drive
metabolism and growth. During darkness, Synechococcus stops growing, derives
energy from its glycogen stores, and greatly decreases rates of macromolecular
synthesis via unknown mechanisms. Here, we show that the stringent response, a
stress response pathway whose genes are conserved across bacteria and plant
plastids, contributes to this dark adaptation. Levels of the stringent response
alarmone guanosine 3'-diphosphate 5'-diphosphate (ppGpp) rise after a shift from
light to dark, indicating that darkness triggers the same response in
cyanobacteria as starvation in heterotrophic bacteria. High levels of ppGpp are
sufficient to stop growth and dramatically alter many aspects of cellular
physiology, including levels of photosynthetic pigments and polyphosphate, DNA
content, and the rate of translation. Cells unable to synthesize ppGpp display
pronounced growth defects after exposure to darkness. The stringent response
regulates expression of a number of genes in Synechococcus, including ribosomal
hibernation promoting factor (hpf), which causes ribosomes to dimerize in the
dark and may contribute to decreased translation. Although the metabolism of
Synechococcus differentiates it from other model bacterial systems, the logic of
the stringent response remains remarkably conserved, while at the same time
having adapted to the unique stresses of the photosynthetic lifestyle.
PMID- 27486248
TI - Wavy membranes and the growth rate of a planar chemical garden: Enhanced
diffusion and bioenergetics.
AB - To model ion transport across protocell membranes in Hadean hydrothermal vents,
we consider both theoretically and experimentally the planar growth of a
precipitate membrane formed at the interface between two parallel fluid streams
in a 2D microfluidic reactor. The growth rate of the precipitate is found to be
proportional to the square root of time, which is characteristic of diffusive
transport. However, the dependence of the growth rate on the concentrations of
hydroxide and metal ions is approximately linear and quadratic, respectively. We
show that such a difference in ionic transport dynamics arises from the enhanced
transport of metal ions across a thin gel layer present at the surface of the
precipitate. The fluctuations in transverse velocity in this wavy porous gel
layer allow an enhanced transport of the cation, so that the effective
diffusivity is about one order of magnitude higher than that expected from
molecular diffusion alone. Our theoretical predictions are in excellent agreement
with our laboratory measurements of the growth of a manganese hydroxide membrane
in a microfluidic channel, and this enhanced transport is thought to have been
needed to account for the bioenergetics of the first single-celled organisms.
PMID- 27486250
TI - Is the learning value of workplace-based assessment being realised? A qualitative
study of trainer and trainee perceptions and experiences.
AB - PURPOSE: Workplace-based assessments (WBAs) were originally intended to inform
learning and development by structuring effective observation-based feedback. The
success of this innovation has not yet been established due in part to the widely
varied tools, implementation strategies and research approaches. Using a
conceptual framework of experience, trajectories and reifications in workplace
learning, we aimed to explore trainer and trainee experiences and perceptions of
the learning value of WBAs. STUDY DESIGN: Trainers and trainees who had used at
least one WBA in the previous year were invited to participate in semistructured
interviews for this phenomenological study. We used a template analysis method to
explore and compare the experiences of the two groups, using the emergent themes
to develop an understanding of the impact of these experiences on perceptions of
learning value. RESULTS: Nine trainers and eight trainees participated in the
study. Common themes emerged among the two groups around issues of responsibility
and engagement along with (mis)understandings of the purpose of the individual
tools. Trainer-specific themes emerged related to the concurrent implementation
of a new e-portfolio and perceptions of increased workload. Trainees associated
WBA with a training structure support value but could not translate experiences
into learning values. CONCLUSIONS: WBAs provide trainees with a justified reason
to approach trainers for feedback. WBAs, however, are not being reified as the
formative assessments originally intended. A culture change may be required to
change the focus of WBA research and reconceptualise this set of tools and
methods as a workplace learning practice.
PMID- 27486251
TI - Dietary non-phytate phosphorus requirement of broilers fed a conventional corn
soybean meal diet from 1 to 21 d of age.
AB - An experiment was conducted to investigate the effect of dietary non-phytate
phosphorus (NPP) level on growth performance, bone characteristics and phosphorus
metabolism-related gene expressions, so as to evaluate the dietary NPP
requirement of broiler chicks fed a conventional corn-soybean meal diet from 1 to
21 d of age. A total of 540 day-old Arbor Acres male chicks were randomly
allocated to one of nine treatments with six replicate cages of 10 birds per cage
in a completely randomized design, and fed a basal corn-soybean meal diet
(containing 0.08% of NPP) supplemented with 0.10, 0.15, 0.25, 0.30, 0.35, 0.40,
0.45, or 0.50% of inorganic phosphorus in the form of CaHPO4.2H2O, respectively.
Each diet contained the constant calcium content of about 1.0%. The results
showed that daily weight gain, serum inorganic P, tibia bone strength, tibia ash
percentage, tibia bone mineral content (BMC) and density (BMD), middle toe ash
percentage, middle toe BMC and BMD were affected (P < 0.0001) by dietary NPP
level, and increased linearly (P < 0.0001) and quadraticly (P < 0.004) as dietary
NPP levels increased. The gene expression of type IIb sodium-phosphate
cotransporter (NaPi-IIb) in the duodenum was affected (P < 0.03) and decreased
linearly (P < 0.002) as dietary NPP levels increased. Dietary NPP requirements
estimated based on fitted broken-line models (P < 0.0001) of the sensitive
indices including daily weight gain, tibia bone strength, tibia ash percentage,
tibia BMC and BMD as well as middle toe ash percentage were 0.34~0.39%. The
results from this study indicate that tibia BMC and BMD might be new, sensitive,
and noninvasive criteria to evaluate the dietary NPP requirements of broilers,
and the dietary NPP requirement is 0.39% for broiler chicks fed a conventional
corn-soybean meal diet from 1 to 21 d of age.
PMID- 27486249
TI - Erasure of DNA methylation, genomic imprints, and epimutations in a primordial
germ-cell model derived from mouse pluripotent stem cells.
AB - The genome-wide depletion of 5-methylcytosines (5meCs) caused by passive dilution
through DNA synthesis without daughter strand methylation and active enzymatic
processes resulting in replacement of 5meCs with unmethylated cytosines is a
hallmark of primordial germ cells (PGCs). Although recent studies have shown that
in vitro differentiation of pluripotent stem cells (PSCs) to PGC-like cells
(PGCLCs) mimics the in vivo differentiation of epiblast cells to PGCs, how DNA
methylation status of PGCLCs resembles the dynamics of 5meC erasure in embryonic
PGCs remains controversial. Here, by differential detection of genome-wide 5meC
and 5-hydroxymethylcytosine (5hmeC) distributions by deep sequencing, we show
that PGCLCs derived from mouse PSCs recapitulated the process of genome-wide DNA
demethylation in embryonic PGCs, including significant demethylation of imprint
control regions (ICRs) associated with increased mRNA expression of the
corresponding imprinted genes. Although 5hmeCs were also significantly diminished
in PGCLCs, they retained greater amounts of 5hmeCs than intragonadal PGCs. The
genomes of both PGCLCs and PGCs selectively retained both 5meCs and 5hmeCs at a
small number of repeat sequences such as GSAT_MM, of which the significant
retention of bisulfite-resistant cytosines was corroborated by reanalysis of
previously published whole-genome bisulfite sequencing data for intragonadal
PGCs. PSCs harboring abnormal hypermethylation at ICRs of the Dlk1-Gtl2-Dio3
imprinting cluster diminished these 5meCs upon differentiation to PGCLCs,
resulting in transcriptional reactivation of the Gtl2 gene. These observations
support the usefulness of PGCLCs in studying the germline epigenetic erasure
including imprinted genes, epimutations, and erasure-resistant loci, which may be
involved in transgenerational epigenetic inheritance.
PMID- 27486252
TI - Technological quality, mineral profile, and sensory attributes of broiler chicken
breasts affected by White Striping and Wooden Breast myopathies.
AB - The aim of the research was to study the impact of white striping and wooden
breast myopathies on the technological quality, mineral, and sensory profile of
poultry meat. With this purpose, a total of 138 breasts were selected for a
control group with normal breasts (N), a group of breasts characterised by white
striping (WS) myopathy, and a group of breasts having both white striping and
wooden breast myopathies (WSWB). Data revealed that the simultaneous presence of
the two myopathies, with respect to the WS lesion individually considered, had a
further detrimental effect on pH (6.04 vs. 5.96; P < 0.05), yellowness (11.4 vs.
10.3; P < 0.01), cooking losses (30.4 vs. 27.6%; P < 0.05), toughness
instrumental values (22.8 vs. 20.0 N; P < 0.01), and perception (6.22 vs. 5.56; P
< 0.01). In addition, mineral contents suggest that a defective ions regulation
is also present in white striping and wooden breast myopathies.
PMID- 27486253
TI - Effects of free-range access on production parameters and meat quality,
composition and taste in slow-growing broiler chickens.
AB - Demand for meat from free-range broiler chickens is increasing in several
countries. Consumers are motivated by better animal welfare and other product
attributes such as quality and taste. However, scientific literature is not
unanimous about whether free-range access influences quality, composition, and
taste of the meat. Because chickens normally do not use free-range areas
optimally, it is possible that provision of more suitable shelter will lead to
more pronounced differences between chickens raised indoors and outdoors. In this
study, an experiment with 2 production rounds of 600 slow-growing broilers each
was performed. In each round, 200 chickens were raised indoors (IN), 200 had free
range access to grassland with artificial shelter (AS), and 200 had free-range
access to short-rotation coppice with willow (SRC). Free-range use, feed intake,
and growth were monitored, and after slaughter (d72) meat quality, composition,
and taste were assessed. Free-range use was higher in SRC than in AS chickens
(42.8 vs. 35.1%, P < 0.001). IN chickens were heavier at d70 than AS and SRC
chickens (2.79 vs. 2.66 and 2.68 kg, P = 0.005). However, feed intake and
conversion did not differ. Breast meat of chickens with free-range access was
darker (P = 0.021) and yellower (P = 0.001) than that of IN chickens. Ultimate pH
was lower (5.73 vs. 5.79; P = 0.006) and drip loss higher (1.29 vs. 1.09%; P =
0.05) in IN versus AS chickens. The percentage of polyunsaturated fatty acids was
higher in AS than in IN meat (35.84 vs. 34.59%; P = 0.021). The taste panel
judged breast meat of SRC chickens to be more tender (P = 0.003) and less fibrous
(P = 0.013) compared to that of AS and IN chickens, and juicier compared to the
IN chickens (P = 0.017). Overall, free-range access negatively affected slaughter
weight, but positively affected meat quality, taste, and composition. Only a few
differences between AS and SRC were found, possibly due to limited differences in
free-range use.
PMID- 27486254
TI - Gluconeogenesis, non-essential amino acid synthesis and substrate partitioning in
chicken embryos during later development.
AB - We aimed to quantify the rate of gluconeogenesis (GNG), non-essential amino-acid
(NEAA) synthesis, and substrate partitioning to the Krebs cycle in embryonic (e)
day e14 and e19 chicken embryos. An in ovo continuous tracer infusion approach
was employed to test the hypotheses that GNG and NEAA synthesis in developing
chicken embryo increases from e14 to e19. [13C6]Glucose or [13C3]glycerol was
continuously infused (8 h) into the chorio-allantoic compartment of eggs on e14
and e19. Glucose entry rate, Cori cycling, and GNG were higher (P < 0.05) in e19
compared to e14 embryos, presumably to support higher glycogen deposition in
liver and muscle. Whereas de novo synthesis of alanine, aspartate, and glutamate
via glycolysis and the Krebs cycle was higher (P < 0.01) in e14 embryos,
synthesis of these NEAA from glycerol was higher (P < 0.05) in e19 compared to
e14 embryos. These patterns of glucose and glycerol utilization suggest a
metabolic shift to conserve glucose for glycogen synthesis and an increased
utilization of yolk glycerol (from triacylglyceride) after e14. Although the
contribution of glycerol to GNG in e19 embryos was higher (P < 0.05) than that in
e14 embryos, the contribution of glycerol to GNG (1.3 to 6.0%) was minor. Based
on [13C6]glucose tracer kinetics, the activities of both pyruvate carboxylase
(PC) and pyruvate dehydrogenase (PDH) in the liver were higher (P < 0.05) in e19
embryos; whereas the higher (P < 0.01) relative activity of liver PC compared to
PDH in e14 embryos suggests a greater anaplerotic flux into the Krebs cycle. In
summary, the in ovo continuous tracer infusion approach allowed for a measurement
of chicken embryo whole body and liver metabolism over a shorter window of
development. This study provided quantitative estimates of the developmental
shifts in substrate utilization, GNG, and NEAA synthesis by chicken embryos, as
well as qualitative estimates of the activities of enzymes central to the Krebs
cycle, glucose, and fatty acid metabolism.
PMID- 27486256
TI - Cooled perch effects on performance and well-being traits in caged White Leghorn
hens.
AB - We assessed the effects of chilled water cooling perches on hen performance and
physiological and behavioral parameters under "natural" high temperatures during
the 2013 summer with a 4-hour acute heating episode. White Leghorns at 16 wk of
age (N = 162) were randomly assigned to 18 cages (n = 9) arranged into 3 units.
Each unit was assigned to one of the 3 treatments through 32 wk of age: 1) cooled
perches, 2) air perches, and 3) no perches. Chilled water (10 degrees C) was
circulated through the cooled perches when cage ambient temperature exceeded 25
degrees C. At the age of 27.6 wk, hens were subjected to a 4-hour acute heating
episode of 33.3 degrees C and plasma corticosterone was determined within 2
hours. Egg production was recorded daily. Feed intake and egg and shell quality
were measured at 5-week intervals. Feather condition, foot health, adrenal and
liver weights, plasma corticosterone, and heat shock protein 70 mRNA were
determined at the end of the study at 32 wk of age. The proportion of hens per
cage perching, feeding, drinking, panting, and wing spreading was evaluated over
one d every 5 wks and on the d of acute heat stress. There were no treatment
effects on the measured physiological and production traits except for nail
length. Nails were shorter for cooled perch hens than control (P = 0.002) but not
air perch hens. Panting and wing spread were observed only on the day of acute
heat stress. The onset of both behaviors was delayed for cooled perch hens, and
they perched more than air perch hens following acute heat stress (P = 0.001) and
at the age 21.4 wk (P = 0.023). Cooled perch hens drank less than control (P =
0.019) but not air perch hens at the age 21.4 wk. These results indicate that
thermally cooled perches reduced thermoregulatory behaviors during acute heat
stress, but did not affect their performance and physiological parameters under
the ambient temperature imposed during this study.
PMID- 27486257
TI - Supplemental effects of probiotic Bacillus subtilis fmbJ on growth performance,
antioxidant capacity, and meat quality of broiler chickens.
AB - This study aimed to investigate the supplemental effects of probiotic Bacillus
subtilis fmbJ (BS fmbJ) on growth performance, antioxidant capacity, and meat
quality of broiler chickens. A total of 240 day-old male Arbor Acres (AA) broiler
chickens were randomly allotted to 4 treatments and raised for 6 wk. Each
treatment had 6 replicate pens with ten birds per replicate. Birds in the control
group (CON) were fed diets without BS fmbJ and antibiotics. The BS groups were
fed the basal diets with BS fmbJ at 2 * 1010 cfu/kg (BS-1 group), BS fmbJ at 3 *
1010 cfu/kg (BS-2 group), BS fmbJ at 4 * 1010 cfu/kg (BS-3 group) without
antibiotics for 42 d. In the study, dietary supplementation with BS fmbJ
significantly improved (P < 0.05) the average daily gain (ADG), average daily
feed intake (ADFI), and feed conversion ratio (FCR) of broilers from 21 to 42 d
and 1 to 42 d. At 42 d, the final body weight was increased (P < 0.05) in BS-2
group compared with that in CON. Dietary BS fmbJ significantly increased (P <
0.05) serum IgA and IgG concentrations of broilers after 42 days raising. The
glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GSH-Px),
and superoxide dismutase (SOD) activity of serum and liver were increased (P <
0.05), and methane dicarboxylic aldehyde (MDA) contents in serum and liver were
decreased (P < 0.05) by BS fmbJ added into the broiler diets. Dietary
supplementation with BS fmbJ significantly decreased (P < 0.05) reactive oxygen
species (ROS) contents in liver mitochondria of broilers. Additionally, the
expression of antioxidant enzyme gene including nuclear factor erythroid 2
related factor 2 (Nrf2), heme oxygenase 1 (HO-1), superoxide dismutase (SOD), and
glutathione peroxidase (GPx) were improved (P < 0.05) by BS fmbJ added into the
broiler diets. Among measuring items of chicken breast meat quality, the drip
loss, cooking loss, shear force, L*24 h, a*24 h, b*45 min, and b*24 h values were
influenced (P < 0.05) by BS fmbJ provided in the diet. Based on these results,
Bacillus subtilis fmbJ could be acted as a beneficial feed additive with
antioxidant capacity in broiler diets.
PMID- 27486255
TI - ALV-J strain SCAU-HN06 induces innate immune responses in chicken primary
monocyte-derived macrophages.
AB - Avian leucosis virus subgroup J (ALV-J) can cause lifelong infection and can
escape from the host immune defenses in chickens. Since macrophages act as the
important defense line against invading pathogens in host innate immunity, we
investigated the function and innate immune responses of chicken primary monocyte
derived macrophages (MDM) after ALV-J infection in this study. Our results
indicated that ALV-J was stably maintained in MDM cells but that the viral growth
rate was significantly lower than that in DF-1 cells. We also found that ALV-J
infection significantly increased nitric oxide (NO) production, but had no effect
on MDM phagocytic capacity. Interestingly, infection with ALV-J rapidly promoted
the expression levels of Myxovirus resistance 1 (Mx) (3 h, 6 h), ISG12 (6 h), and
interleukin-1beta (IL-1beta) (3 h, 12 h) at an early infection stage, whereas it
sharply decreased the expression of Mx (24 h, 36 h), ISG12 (36 h), and made
little change on IL-1beta (24 h, 36 h) production at a late infection stage in
MDM cells. Moreover, the protein levels of interferon-beta (IFN-beta) and
interleukin-6 (IL-6) had sharply increased in infected MDM cells from 3 to 36 h
post infection (hpi) of ALV-J. And, the protein level of interleukin-10 (IL-10)
was dramatically decreased at 36 hpi in MDM cells infected with ALV-J. These
results demonstrate that ALV-J can induce host innate immune responses and we
hypothesize that macrophages play an important role in host innate immune attack
and ALV-J immune escape.
PMID- 27486258
TI - Intermolecular disulfide bond influences unphosphorylated STAT3 dimerization and
function.
AB - Signal transducer and activator of transcription 3 (STAT3) is a transcription
factor activated by the phosphorylation of tyrosine 705 in response to many
cytokines and growth factors. Recently, the roles for unphosphorylated STAT3 (U
STAT3) have been described in response to cytokine stimulation, in cancers, and
in the maintenance of heterochromatin stability. It has been reported that U
STAT3 dimerizes, shuttles between the cytoplasm and nucleus, and binds to DNA,
thereby driving genes transcription. Although many reports describe the active
role of U-STAT3 in oncogenesis in addition to phosphorylated STAT3, the U-STAT3
functional pathway remains elusive.In this report, we describe the molecular
mechanism of U-STAT3 dimerization, and we identify the presence of two
intermolecular disulfide bridges between Cys367 and Cys542 and Cys418 and Cys426,
respectively. Recently, we reported that the same cysteines contribute to the
redox regulation of STAT3 signaling pathway both in vitro and in vivo The
presence of these disulfides is here demonstrated to largely contribute to the
structure and the stability of U-STAT3 dimer as the dimeric form rapidly
dissociates upon reduction in the S-S bonds. In particular, the Cys367-Cys542
disulfide bridge is shown to be critical for U-STAT3 DNA-binding activity.
Mutation of the two Cys residues completely abolishes the DNA-binding capability
of U-STAT3. Spectroscopic investigations confirm that the noncovalent
interactions are sufficient for proper folding and dimer formation, but that the
interchain disulfide bonds are crucial to preserve the functional dimer. Finally,
we propose a reaction scheme of U-STAT3 dimerization with a first common step
followed by stabilization through the formation of interchain disulfide bonds.
PMID- 27486259
TI - Triggering safer general practice care.
PMID- 27486260
TI - Novel folliculin (FLCN) mutation and familial spontaneous pneumothorax.
AB - BACKGROUND: Familial spontaneous pneumothorax is one of the characteristics of
Birt-Hogg-Dube syndrome (BHDS), which is an autosomal dominant disease caused by
the mutation of folliculin (FLCN). AIM: To investigate the mutation of FLCN gene
in a familial spontaneous pneumothorax. DESIGN: Prospective case study. METHODS:
Clinical and genetic data of a Chinese family with four patients who presented
spontaneous pneumothorax in the absence of skin lesions or renal tumors were
collected. CT scan of patient's lung was applied for observation of pneumothorax.
DNA sequencing of the coding exons (4-14 exons) of FLCN was performed for all 11
members of the family and 100 unrelated healthy controls. RESULTS: CT scan of
patient's lung showed spontaneous pneumothorax. A mutation (c. 510C > G) that
leads to a premature stop codon (p. Y170X) was found in the proband using DNA
sequencing of coding exons (4-14 exons) of FLCN. This mutation was also observed
in the other affected members of the family. CONCLUSIONS: A nonsense mutation of
FLCN was found in a spontaneous pneumothorax family. Our results expand the
mutational spectrum of FLCN in patients with BHDS.
PMID- 27486261
TI - 'The old guessing tube': 200 years of the stethoscope.
PMID- 27486262
TI - Dementia in the acute hospital: the prevalence and clinical outcomes of acutely
unwell patients with dementia.
AB - BACKGROUND: Studies have demonstrated that a significant minority of older
persons presenting to acute hospital services are cognitively impaired; however,
the impact of dementia on long-term outcomes is less clear. AIM: To evaluate the
prevalence of dementia, both formally diagnosed and hitherto unrecognised in a
cohort of acutely unwell older adults, as well as its impact on both immediate
outcomes (length of stay and in-hospital mortality) and 12-month outcomes
including readmission, institutionalisation and death. DESIGN: Prospective
observational study. METHODS: 190 patients aged 70 years and over, presenting to
acute hospital services underwent a detailed health assessment including
cognitive assessment (standardised Mini Mental State Examination, AD8 and
Confusion Assessment Method for the Intensive Care Unit). Patients or informants
were contacted directly 12 months later to compile 1-year outcome data. Dementia
was defined as a score of 2 or more on the AD8 screening test. RESULTS: Dementia
was present in over one-third of patients (73/190). Of these patients, 36%
(26/73) had a prior documented diagnosis of dementia with the remaining
undiagnosed before presentation. The composite outcome of death or readmission to
hospital within the following 12 months was more likely to occur in patients with
dementia (73% (53/73) vs. 58% (68/117), P = 0.043). This finding persisted after
controlling for age, gender, frailty status and medical comorbidities, including
stroke and heart disease. CONCLUSION: A diagnosis of dementia confers an
increased risk of either death or further admission within the following 12
months, highlighting the need for better cognitive screening in the acute
setting, as well as targeted intervention such as comprehensive geriatric
assessment.
PMID- 27486263
TI - Using routine blood test results to predict the risk of death for emergency
medical admissions to hospital: an external model validation study.
AB - BACKGROUND: The Biochemistry and Haematology Outcome Model (BHOM) relies on the
results from routine index blood tests to predict the patient risk of death. We
aimed to externally validate the BHOM model. METHOD: We considered all emergency
adult medical patients who were discharged from Northern Lincolnshire and Goole
(NLAG) hospital in 2014. We compared patient characteristics between NLAG (the
validation sample) and the hospital where BHOM was developed. We evaluated the
predictive performance, according to discriminative ability (with a concordance
statistic, c), and calibration (agreement between observed and predicted risk).
RESULT: There were 29 834 emergency discharges of which 24 696 (83%) had complete
data. In comparison with the development sample, the NLAG sample was similar in
age, blood test results, but experienced a lower mortality (4.7 vs. 8.7%). When
applied to NLAG, the BHOM model had good discrimination (c-statistic 0.83 [95% CI
0.823-0.842]). Calibration was good overall, although the BHOM model
overpredicted for lowest (<5%, observed = 229, predicted = 286) and highest
(>=50%, observed = 31, predicted = 49) risk groups, even after recalibrating for
the differences in baseline risk of death. CONCLUSION: Differences in patient
case-mix profile and baseline risk of death need to be considered before the BHOM
model can be used in another hospital. After re-calibrating for the baseline
difference in risk the BHOM model had good discrimination but less adequate
calibration.
PMID- 27486264
TI - The role of syncytins in human reproduction and reproductive organ cancers.
AB - Human life begins with sperm and oocyte fusion. After fertilization, various
fusion events occur during human embryogenesis and morphogenesis. For example,
the fusion of trophoblastic cells constitutes a key process for normal placental
development. Fusion in the placenta is facilitated by syncytin 1 and syncytin 2.
These syncytins arose from retroviral sequences that entered the primate genome
25 million and more than 40 million years ago respectively. About 8% of the human
genome consists of similar human endogenous retroviral (HERVs) sequences. Many
are inactive because of mutations or deletions. However, the role of the few that
remain transcriptionally active has not been fully elucidated. Syncytin proteins
maintain cell-cell fusogenic activity based on ENV: gene-mediated viral cell
entry. In this review, we summarize how syncytins and their receptors are
involved in fusion events during human reproduction. The significance of
syncytins in tumorigenesis is also discussed.
PMID- 27486265
TI - The evolution of the placenta.
AB - The very apt definition of a placenta is coined by Mossman, namely apposition or
fusion of the fetal membranes to the uterine mucosa for physiological exchange.
As such, it is a specialized organ whose purpose is to provide continuing support
to the developing young. By this definition, placentas have evolved within every
vertebrate class other than birds. They have evolved on multiple occasions, often
within quite narrow taxonomic groups. As the placenta and the maternal system
associate more intimately, such that the conceptus relies extensively on maternal
support, the relationship leads to increased conflict that drives adaptive
changes on both sides. The story of vertebrate placentation, therefore, is one of
convergent evolution at both the macromolecular and molecular levels. In this
short review, we first describe the emergence of placental-like structures in
nonmammalian vertebrates and then transition to mammals themselves. We close the
review by discussing the mechanisms that might have favored diversity and hence
evolution of the morphology and physiology of the placentas of eutherian mammals.
PMID- 27486266
TI - Seminal vesicle proteins SVS3 and SVS4 facilitate SVS2 effect on sperm
capacitation.
AB - Mammalian spermatozoa acquire their fertilizing ability in the female
reproductive tract (sperm capacitation). On the other hand, seminal vesicle
secretion, which is a major component of seminal plasma, inhibits the initiation
of sperm capacitation (capacitation inhibition) and reduces the fertility of the
capacitated spermatozoa (decapacitation). There are seven major proteins involved
in murine seminal vesicle secretion (SVS1-7), and we have previously shown that
SVS2 acts as both a capacitation inhibitor and a decapacitation factor, and is
indispensable for in vivo fertilization. However, the effects of SVSs other than
SVS2 on the sperm have not been elucidated. Since mouse Svs2-Svs6 genes evolved
by gene duplication belong to the same gene family, it is possible that SVSs
other than SVS2 also have some effects on sperm capacitation. In this study, we
examined the effects of SVS3 and SVS4 on sperm capacitation. Our results showed
that both SVS3 and SVS4 are able to bind to spermatozoa, but SVS3 alone showed no
effects on sperm capacitation. On the other hand, SVS4 acted as a capacitation
inhibitor, although it did not show decapacitation abilities. Interestingly, SVS3
showed an affinity for SVS2 and it facilitated the effects of SVS2. Interaction
of SVS2 and spermatozoa is mediated by the ganglioside GM1 in the sperm membrane;
however, both SVS3 and SVS4 had weaker affinities for GM1 than SVS2. Therefore,
we suggest that separate processes may cause capacitation inhibition and
decapacitation, and SVS3 and SVS4 act on sperm capacitation cooperatively with
SVS2.
PMID- 27486268
TI - BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian
disease development.
AB - Cystic ovarian disease (COD) is an important cause of subfertility in dairy
cattle. Bone morphogenetic proteins (BMPs), mainly BMP2, BMP4 and BMP6, play a
key role in female fertility. In this study, we hypothesized that an altered BMP
system is associated with ovarian alterations contributing to COD pathogenesis.
Therefore, we examined the expression of BMP2, BMP4 and BMP6 and BMP receptor 1B
(BMPR1B) in the ovaries of animals with spontaneous or ACTH-induced COD, as well
as during the development of the disease, in a model of follicular persistence
induced by low doses of progesterone (at 5, 10 and 15 days of follicular
persistence). Results showed changes in BMP2, BMP4 and BMP6 expression during
folliculogenesis, in granulosa and theca cells in the COD groups, as well as at
different stages of follicular persistence. Results also showed changes in BMPR1B
expression in developing follicles in animals with COD, and at the initial stages
of follicular persistence (P5). Comparison between groups showed significant
differences, mainly in BMP4 and BMP6 expression, in granulosa and theca cells of
different follicular categories. The expression of these BMPs also increased in
cystic and persistent follicles, in relation to antral follicles of the control
group. BMPR1B showed high expression in cystic follicles. Together, these results
may indicate an alteration in BMPs, especially in BMP4 and BMP6, as well as in
BMPR1B, which occurs early in folliculogenesis and incipiently during the
development of COD, which could be a major cause of recurrence of this disease in
cattle.Free Spanish abstract: A Spanish translation of this abstract is freely
available at http://www.reproduction-online.org/content/early/2016/08/01/REP-15
0315/suppl/DC1.
PMID- 27486267
TI - Ectopic POU5F1 in the male germ lineage disrupts differentiation and
spermatogenesis in mice.
AB - Expression levels of the pluripotency determinant, POU5F1, are tightly regulated
to ensure appropriate differentiation during early embryogenesis. POU5F1 is also
present in the spermatogonial stem cell/progenitor cell population in mice and it
is downregulated as spermatogenesis progresses. To test if POU5F1 downregulation
is required for SSCs to differentiate, we produced transgenic mice that
ubiquitously express POU5F1 in Cre-expressing lineages. Using a Vasa-Cre driver
to produce ectopic POU5F1 in all postnatal germ cells, we found that POU5F1
downregulation was necessary for spermatogonial expansion during the first wave
of spermatogenesis and for the production of differentiated spermatogonia capable
of undergoing meiosis. In contrast, undifferentiated spermatogonia were
maintained throughout adulthood, consistent with a normal presence of POU5F1 in
these cells. The results suggest that POU5F1 downregulation in differentiating
spermatogonia is a necessary step for the progression of spermatogenesis.
Further, the creation of a transgenic mouse model for conditional ectopic
expression of POU5F1 may be a useful resource for studies of POU5F1 in other cell
lineages, during tumorogenesis and cell fate reprogramming.
PMID- 27486270
TI - Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT
and ERK pathways.
AB - Intrauterine adhesions are common acquired endometrial syndromes secondary to
endometrial injury, with limited effective therapies. Recently, several studies
have reported that bone marrow stem cells (BMSCs) could repair injured
endometrium in animal experiments. However, the role of stem cells in endometrial
injury repair and its therapeutic mechanisms remain unclear. Here, we established
mouse endometrial injury model and examined the benefit of human endometrial
mesenchymal stem cells derived from menstrual blood (MenSCs) in restoration of
injured endometrium. Injured endometrium exhibited significantly accelerated
restoration at Day 7 after MenSCs transplantation, with increased endometrial
thickness and microvessel density. Moreover, the fertility of mice with injured
endometrium was improved, with higher conception rate (53.57% vs 14.29%, P =
0.014) and larger embryo number (3.1 +/- 0.6 vs 0.9 +/- 0.7, P = 0.030) in MenSCs
group than control group, while no difference was found in undamaged horns
between two groups. Conditioned medium from MenSCs (MenSCs-CM) could decrease
H2O2-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and
promote proliferation, migration and angiogenesis. Angiogenesis effect of MenSCs
CM was also confirmed in Matrigel plug assay in mice. Furthermore, we discovered
that MenSCs-CM could activate AKT and ERK pathways and induce the overexpression
of eNOS, VEGFA, VEGFR1, VEGFR2 and TIE2 in HUVECs, which are critical in MenSCs
CM-induced angiogenesis. Angiogenesis induced by MenSCs-CM could be reversed by
inhibitors of AKT and/or ERK. Taken together, we concluded that MenSCs could
restore injured endometrium and improve the fertility of the endometrial injury
mice, which was partially attributed to angiogenesis induced by MenSCs.
PMID- 27486269
TI - Rhox13 is required for a quantitatively normal first wave of spermatogenesis in
mice.
AB - We previously described a novel germ cell-specific X-linked reproductive homeobox
gene (Rhox13) that is upregulated at the level of translation in response to
retinoic acid (RA) in differentiating spermatogonia and preleptotene
spermatocytes. We hypothesize that RHOX13 plays an essential role in male germ
cell differentiation, and have tested this by creating a Rhox13 gene knockout
(KO) mouse. Rhox13 KO mice are born in expected Mendelian ratios, and adults have
slightly reduced testis weights, yet a full complement of spermatogenic cell
types. Young KO mice (at ~7-8 weeks of age) have a ~50% reduction in epididymal
sperm counts, but numbers increased to WT levels as the mice reach ~17 weeks of
age. Histological analysis of testes from juvenile KO mice reveals a number of
defects during the first wave of spermatogenesis. These include increased
apoptosis, delayed appearance of round spermatids and disruption of the precise
stage-specific association of germ cells within the seminiferous tubules.
Breeding studies reveal that both young and aged KO males produce normal-sized
litters. Taken together, our results indicate that RHOX13 is not essential for
mouse fertility in a controlled laboratory setting, but that it is required for
optimal development of differentiating germ cells and progression of the first
wave of spermatogenesis.
PMID- 27486271
TI - Effects of neonatal exposure to a glyphosate-based herbicide on female rat
reproduction.
AB - In this study, we investigated whether neonatal exposure to a glyphosate-based
herbicide (GBH) alters the reproductive performance and the molecular mechanisms
involved in the decidualization process in adult rats. Newborn female rats
received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7.
On PND90, the rats were mated to evaluate (i) the reproductive performance on
gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology,
endometrial cell proliferation, apoptosis and cell cycle regulators, and
endocrine pathways that regulate uterine decidualization (steroid receptors/COUP
TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group
showed a significant increase in the number of resorption sites on GD19,
associated with an altered decidualization response. In fact, on GD9, the GBH
treated rats showed morphological changes at the IS, associated with a decreased
expression of estrogen and progesterone receptors, a downregulation of COUP-TFII
(Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation
marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial
decidualization might be the mechanism of GBH-induced post-implantation embryo
loss.
PMID- 27486272
TI - Uterine flushing proteome of the tammar wallaby after reactivation from diapause.
AB - The marsupial tammar wallaby has the longest period of embryonic diapause of any
mammal, up to 11 months, during which there is no cell division or blastocyst
growth. Since the blastocyst in diapause is surrounded by acellular coats, the
signals that maintain or terminate diapause involve factors that reside in
uterine secretions. The nature of such factors remains to be resolved. In this
study, uterine flushings (UFs) were used to assess changes in uterine secretions
of tammars using liquid chromatography-mass spectrometry (LC-MS/MS) during
diapause (day 0 and 3) and reactivation days (d) 4, 5, 6, 8, 9, 11 and 24 after
removal of pouch young (RPY), which initiates embryonic development. This study
supports earlier suggestions that the presence of specific factors stimulate
reactivation, early embryonic growth and cell proliferation. A mitogen, hepatoma
derived growth factor and soluble epidermal growth factor receptors were observed
from d3 until at least d11 RPY when these secreted proteins constituted 21% of
the UF proteome. Binding of these factors to specific cellular receptors or
growth factors may directly stimulate DNA synthesis and division in endometrial
gland cells. Proteins involved in the p53/CDKN1A (p21) cell cycle inhibition
pathway were also observed in the diapause samples. Progesterone and most of the
oestrogen-regulated proteins were present in the UF after d3, which is
concomitant with the start of blastocyst mitoses at d4. We propose that once the
p21 inhibition of the cell cycle is lost, growth factors including HDGF and EGFR
are responsible for reactivation of the diapausing blastocyst via the uterine
secretions.
PMID- 27486273
TI - Getting Older Women Pregnant: Contemporary Thoughts.
AB - For women of advanced age with abnormally increased FSH levels, standardized
hormonal stimulation often represents a cost-intensive procedure with a low
success rate. It is well established now that with mild ovarian stimulation,
there is a greater percentage of good-quality eggs (although a smaller number)
than with higher-dose conventional stimulation. Mild stimulation protocols reduce
the mean number of days of stimulation, the total amount of gonadotropins used
and the mean number of oocytes retrieved. The proportion of high-quality and
euploid embryos seems to be higher compared with conventional stimulation
protocols, and the pregnancy rate per embryo transfer is comparable. Moreover,
the reduced costs, the better tolerability for patients and the less time needed
to complete an IVF cycle make mild approaches clinically and cost-effective over
a given period of time. The low number of embryos available for transfer poses a
great challenge in the management of older women going in for IVF. A potential
management of these older women is to create a sufficient pool of embryos by
accumulating vitrified good-grade embryos over several minimal stimulation and
natural cycles. At the end of the accumulation process, these embryos can be
subjected to a preimplantation genetic screening using next-generation sequencing
and then the pool would have only chromosomal normal embryos with maximal chances
of implantation. This would potentially make the chances of success for older
women similar to normal responders. This management, however, is unthinkable
without an outstanding vitrification program. The option of accumulating embryos
has become a promising reality with the advent of vitrification technologies.
PMID- 27486274
TI - An Epidemiology Study to Determine the Prevalence and Risk Factors Associated
with Recurrent Spontaneous Miscarriage in India.
AB - BACKGROUND: The data on the prevalence of recurrent spontaneous miscarriage (RSM)
in India are scarce. This study aimed to determine the prevalence of RSM in
Indian females. METHODS: Female patients aged between 18 and 45 years with
history of at least one spontaneous miscarriage were enrolled in the study. The
probability of a subsequent miscarriage after the first, second, and third
miscarriage was determined. The prevalence of RSM (defined as loss of >=3
pregnancies of <=20 weeks gestation each) between different age groups was
compared using chi (2) test. Binary logistic regression analysis was applied to
determine any association between RSM and the presence of risk factors. RESULTS:
Of the 2398 patients screened for eligibility, 767 (32 %) had a history of at
least one spontaneous miscarriage. The prevalence of RSM among the 753 enrolled
patients who satisfied the eligibility criteria in the study was 7.46 %. RSM was
mostly recorded in the age group of >=33 years (14.68 %, n = 32). In patients
with RSM, the second and third miscarriages were more prevalent during 7th week
to end of 11th week of gestation. The probability of having a subsequent
miscarriage after the first, second, and third miscarriage was 0.25, 0.34, and
0.22, respectively. There was a significant association (p < 0.05) between RSM
and clotting disorders, immunological factors, infections, and genetic disorders.
CONCLUSION: The study revealed a higher prevalence of RSM among the Indian women
as compared to western data. Age, clotting disorders, immunological factors,
infections, and genetic disorders were the significant risk factors associated
with RSM.
PMID- 27486275
TI - Types and Outcome of Fetal Urinary Anomalies in Low Resource Setting Countries: A
Retrospective Study.
AB - BACKGROUND: Congenital anomalies of the kidney and urinary tract in the
developing countries have a poor prognosis due to limited experience in antenatal
and postnatal management. PATIENTS AND METHODS: A 3-year retrospective study was
carried out from January 2011 to December 2013. The following data were collected
and analyzed: maternal age, gravidity, parity, gestational age at diagnosis, and
ultrasonography findings. Final diagnosis after birth, the performed surgeries,
follow-up data, as well as survival at one year were also analyzed. RESULTS: The
mean age of the included patients was 28 years (range 20-35 years). The mean
parity was 1.7 (range 0-4). The mean gestational age at diagnosis was 26 weeks
(range 15-36 weeks). Consanguinity was reported in 10 cases (24.4 %). There were
25 males and 16 females. Bilateral renal agenesis was the commonest type (19.5
%). The anomalies of kidneys and urinary tract in our cases were associated with
other anomalies in 8 cases (19.5 %). Oligohydramnios was detected in bilateral
renal agenesis and posterior urethral valve. Surgical interference during the
first 6 months was performed in 6 cases; pyeloplasty for unilateral or bilateral
hydronephrosis was performed in 5 cases; and excision of solitary renal cyst
performed in one case. By the end of the first year, two of the three cases with
chronic renal disease, who were under peritoneal dialysis, died, and three cases
who had undergone pyeloplasty were lost to follow-up. CONCLUSION: Among the 41
cases with antenatally diagnosed renal and urinary malformations; bilateral renal
agenesis was the commonest anomaly (19.5 %). There were high rates of induction
of abortion, IUFD, and neonatal deaths. The poor outcome may be due to lack of
experience in performing invasive therapeutic fetal procedures.
PMID- 27486276
TI - Pregnancy Outcome in Women with Mechanical Prosthetic Heart Valves Treated with
Unfractionated Heparin (UFH) or Enoxaparin.
AB - OBJECTIVE: This study was carried out to determine the maternal (including
thromboembolic and hemorrhagic complications) and fetal outcomes (including
miscarriage, stillbirth, baby death, and live birth) in women with mechanical
heart valves managed with therapeutic doses of unfractionated heparin (UFH)
versus enoxaparin during pregnancy. METHODS: This is a prospective comparative,
nonrandomized study. Pregnant women with mechanical heart valves presenting to
high-risk pregnancy unit of Benha University Hospital, Egypt were treated with
UFH 15,000 U/12 h versus enoxaparin (Clexane) 1 mg/kg SC/12 h during pregnancy
and the results were analyzed. RESULTS: 40 pregnant women were included in the
study. In 20 pregnant women, anticoagulation was with UFH, and 20 pregnant women
received enoxaparin. One (3 %) thrombotic complication occurred with enoxaparin
treatment. Noncompliance or subtherapeutic levels contributed to this outcome in
this case. Antenatal hemorrhage occurred in 4 (10 %) and postpartum hemorrhagic
complications in 5 (12.5 %) pregnancies. Of the 32 pregnant women who continued
after 20 weeks' gestation, 100 % (17/17) of the women taking predominantly UFH
had a surviving infant compared with 93 % (14/15) of the women taking primarily
enoxaparin (p = 0.25). One intrauterine fetal death occurred in the enoxaparin
group. There was no significant difference in the live birth rates between the
two groups (p = 0.31). CONCLUSIONS: Compliance with therapeutic dose of UFH
during pregnancy in women with mechanical heart valves is associated with a low
risk of valve thrombosis and good fetal outcomes, but meticulous monitoring is
essential.
PMID- 27486277
TI - The Paraoxonase 1 Arylesterase Activity, Total Oxidative Stress, Nitric Oxide and
Vitamin C Levels in Maternal Serum, and Their Relation to Birth Weight of
Newborn.
AB - AIM: Aim of this study is to find out clinical relevance of estimating PON1
arylesterase activity, total oxidative stress (TOS), nitric oxide (NO), and
vitamin C levels in maternal serum for prediction of birth weight of newborn.
METHODS: We have investigated the PON1 arylesterase activity, TOS, NO, vitamin C,
total protein, and albumin levels in 56 postnatal clinic patients having newborn
weighing <2500 gm (low birth weight) and compared with 56 postnatal clinic
patients having newborn weighing >2500 gm. Samples were collected immediately
after delivery. RESULTS: PON1 arylesterase activity levels show significant
decrease in cases as compared to controls (93.27 +/- 13.76 kU/l vs. 112.77 +/-
9.42 kU/l). Nitric oxide (nitrate + nitrite) levels are also found to be
significantly decreased in cases with respect to controls (22.89 +/- 2.65 umol/l
vs. 24.73 +/- 3.80 umol/l). Total oxidative stress is significantly increased in
cases than in control subjects (23.34 +/- 2.64 MUmol H2O2 equiv./l vs. +/- 21.43
+/- 2.47 MUmol H2O2 equiv/l). Vitamin C levels are also significantly decreased
in cases as compared to controls (1.23 +/- 0.25 mg/dl vs. 1.34 +/- 0.28 mg/dl).
Positive correlation between neonatal birth weight and maternal serum PON1
arylesterase activity (r = 0.682, p < 0.05) while negative correlation is
obtained between neonatal birth weight and maternal serum oxidative stress (r =
0.478, p < 0.05). Logistic regression analysis is applied for assessing
predictive utility which demonstrated a significant association of birth weight
with PON1 arylesterase activity (AUC = 0.960, Naglekerke's R (2) = 0.793, p <
0.05). CONCLUSION: Decreased arylesterase activity and antioxidant vitamin C
levels with increased total oxidative stress in maternal serum may be considered
as the additional risk factors for the development of low birth weight newborn.
PMID- 27486278
TI - Gonadotropin Alone is a Better Drug for Ovarian Stimulation than in Combination
with Clomiphene in Intrauterine Insemination.
AB - OBJECTIVE: This study compares the efficacy of sequential clomiphene citrate (CC)
+ Gonadotropin to that of Gonadotropin alone with ultrasound monitoring. METHODS:
It is a retrospective analytic study done on a total of 100 couples to compare
two groups receiving CC + Gonadotropin and Gonadotropin alone for ovarian
stimulation followed by intrauterine Insemination (IUI). We studied the cycle
performance parameters. Cumulative pregnancy rates and ovulation rates were the
primary outcomes. Results were analyzed following the intention-to-treat
principle. RESULTS: There were no significant differences with respect to
indications and the numbers of dominant follicles recruited. The endometrial
thickness was significantly better in Gonadotropin-alone group (P < 0.05).
Ovulation rate was better for CC + Gonadotropin at 95.91 %. Nine pregnancies were
in the CC + Gonadotropin group (18.36 %) and 17 in Gonadotropin-alone group (33.3
%). CONCLUSIONS: Significant differences in pregnancy rates and endometrial
thickness were seen. Gonadotropin alone thus appears to give better results, but
CC + Gonadotropin seems to be a cost-effective drug.
PMID- 27486279
TI - Role of PET-CT Scan in Gynaeconcology.
AB - THE PURPOSE OF THIS STUDY: This study was undertaken to evaluate the role of
positron emission tomography-CT (PET-CT) in diagnosis and management of
gynecological malignancies in primary and recurrent settings and also to
investigate its role in inappropriately treated patients, for pretreatment
evaluation (staging) to help in proper therapeutic management. METHOD: This is a
retrospective study of 56 patients of gynecological malignancy registered in
Gujarat Cancer Research Institute from June 2011 to December 2013. RESULTS: Out
of 56 cases where PET was done, the results were as follows: carcinoma cervix-23,
carcinoma ovary-20, carcinoma endometrium-9, carcinoma vulva-1, carcinoma vagina
2, and GTN-1. PET scan was negative in 37 % of patients where CT scan was
suspicious, which changed the therapeutic modality and prevented further
unnecessary interventions. In cases where clinical suspicion of recurrence was
high based on rising tumor marker and CT scan was negative, subsequent PET-CT was
able to pick up malignancy in 75 % cases. Eleven patients (25 %) with suspected
recurrence with inconclusive CT scan and negative PET-CT scan were kept on follow
up, thus reducing further morbidity and cost. CONCLUSION: Addition of PET-CT, a
noninvasive method to the oncologist's imaging armamentarium may ultimately
improve both outcomes and costs by altering management strategies in primary and
recurrent settings. The potential use of PET-CT appears promising in several
decision-making steps in the management of patients with gynecological
malignancy. It defines the extent of metastatic disease which enables the
clinician to decide regarding salvageable surgical intervention or palliative
measures.
PMID- 27486281
TI - Defining the Role of Neoadjuvant Chemotherapy Followed by Surgery in Locally
Advanced Cancer Cervix: A Meta-analysis of Phase III Trials.
AB - STUDY OBJECTIVES: This meta-analysis was performed to compare the outcomes
between NACT-S and RT for locally advanced cancer cervix. The primary end points
were survival benefits. SEARCHING METHOD: The data sources for the search
included medline, national library of medicine, and the embase search engines.
Inclusion criteria included studies published between 2000 and 2012, and FIGO
stages IB2 to IVA. Studies had to be properly randomized, prospective, or
retrospective and only phase III. Further, the studies had to be with two arms,
including one arm for neoadjuvant chemotherapy then-surgery (NACT-S), and the
other arm for radiotherapy (RT). RESULTS: Data were collected from 1171 patients
enrolled in seven phase III trials. The 5-year PFS (progression-free survival)
for NACT-S and RT were 62 and 45.5 %, respectively. The 5-year OS for NACT-S and
RT were 66 and 49 %, respectively. NACT-S was associated with better late
toxicities compared to RT. CONCLUSION: NACT-S is a reasonable treatment option
for locally advanced cancer cervix. It achieved better results than RT,
especially for stages from IB2 to IIB.
PMID- 27486280
TI - Outcome Analysis of Day-3 Frozen Embryo Transfer v/s Fresh Embryo Transfer in
Infertility: A Prospective Therapeutic Study in Indian Scenario.
AB - INTRODUCTION: Advanced fertilization techniques like frozen embryo transfer (FET)
and assisted reproductive technology have become popular and commonly used
methods to treat patients suffering from infertility. Incidences of infertility
are on a rise due to increased representation of females in the work place, delay
in marriages, stress, and ignorance. METHODS: We performed this prospective
therapeutic study to compare FET and fresh embryo transfer in the treatment of
infertility in terms of conception rate, patient acceptance, complications, and
patient's compliance. A prospective screening therapeutic study on 108 patients,
from September 2013 to September 2014 in Karnataka, India, randomized the
patients into 2 groups (n = 54), Group-I treated with day-3 FET while Group-II
was treated with fresh embryo transfer, after performing ICSI. RESULTS: In 108
patients, 45 % patients were within 35 years of age, 35 % were in the age group
35-39. Significantly, 22 (40.75 %) patients treated with FET conceived (P =
0.022), whereas 16 (29.63 %) patients treated with fresh embryo transfer
conceived (P = 0.59). DISCUSSION: There is limited published literature from the
subcontinent, comparing techniques like FET and embryo transfers in the treatment
of infertility. Awareness and economic reforms must be formulated in India to
facilitate individuals facing infertility problems to conceive. CONCLUSION: FET
has better and significant conception rates compared to fresh embryo transfers.
FET shares an advantage of providing good quality embryos for future and
subsequent implantations in cases of failure. Patient counseling and motivation
play a pivotal role in the success of therapeutic procedure.
PMID- 27486282
TI - Unusual Metastasis from Carcinoma Cervix.
AB - INTRODUCTION: Although the incidence of cancer cervix has reduced in India during
the last two decades, still most of the patients presenting in tertiary care
centers are in advanced stages. MATERIAL AND METHODS: At this center, we see 6%
of cancer cervix cases every year, and most of these cases are in stage III and
IVa. All these patients have squamous cell carcinoma and were treated with a
combination of external and intracavitary radiotherapy along with concurrent
cisplatin given once weekly. Eighty-nine point nine % patients had achieved a
complete response. RESULTS: Local recurrence was seen in 17.9% at a median
duration of 10.5 months, and 8.17% developed distant metastasis involving lung,
liver, bone, and supraclavicular lymph nodes. Three patients developed metastasis
at unusual sites involving breast, paraspinal muscles, and duodenum which are
very rarely involved. These patients were treated with chemotherapy using
carboplatin and Paclitaxel combination but succumbed within 8-10 months of
development of metastasis. CONCLUSION: The cause of involvement of these unusual
sites is not clear, but it may be hematological spread, and we want to share
these reports such that these sites are seen during follow-up of patients of
cancer cervix.
PMID- 27486283
TI - Prognostic Factors in Primary Vaginal Cancer: A Single Institute Experience and
Review of Literature.
AB - BACKGROUND: Primary vaginal carcinoma is rare, accounting for 1-2 % of all
gynecological malignancies. Being rare, most observations are based on
retrospective and comparative analyses. This study was aimed to retrospectively
analyze the prognostic factors and its relevance in the outcomes of primary
vaginal cancers. MATERIALS: Medical records of all cases of primary vaginal
cancers, presented to Department of Oncology, from 2004 to 2012, at a tertiary
care center in southern India, were retrieved from electronic medical records,
and were analyzed. RESULTS: The total number of cases was 32. Median age at
presentation was 64.28 years. Squamous histology accounted for 84.4 %, with the
rest being adenocarcinoma. Surgery was offered for five (15.6 %), and concurrent
chemotherapy for 14 (43.8 %) patients. Three patients had only surgery. All
others received radiotherapy. Twenty received external beam radiation (EBRT) and
vaginal brachytherapy (VBT); seven only EBRT and two, adjuvant radiation. Five
patients had residual disease; two, stage III, and three stage IV. Median follow
up was 55.83 months. Twelve patients were alive at last follow-up (37.5 %), while
14 were dead (43.8 %-8 of disease and 6 of other causes). Six patients were lost
to follow-up (18.8 %). Twenty patients were disease free. Seven had recurrence,
three loco-regional and four distant. Median overall survival (OS) was 86.1
months, disease-free survival (DFS) 90.17 months, and disease-specific survival
(DSS) 97.13 months. When well and moderately differentiated tumors were taken
together, the 5-year OS, DFS, and DSS rates were, 56.6, 64.3, and 82.3 %. For
poorly differentiated tumors, median OS, DFS, and DSS were, 20.9, 14.6, and 20.9
months, with statistically significant advantage for better grade tumors, for DSS
(p 0.050). Better 5-year OS, DFS, and DSS rates were observed for stage I + II
group, with 54.9, 79.8, and 78.9 %, compared with advanced stage where the same
were 54.8, 38.2, and 68.6 % (DFS-p 0.003, DSS-p 0.009). Grade and stage of tumor
had statistically significant predictive value over the outcomes, while tumor
size showed a significant trend. Patients treated with combination of EBRT and
VBT fared well. CONCLUSION: Our study could conclude that grade of
differentiation was a significant predictor of poor survival as was stage of
disease. Combination of VBT and external beam radiotherapy provides good DFS.
PMID- 27486284
TI - Induction Chemotherapy Followed by Concurrent Chemoradiation in the Management of
Different Stages of Cervical Carcinoma: 5-year Retrospective Study.
AB - AIM: The data of survival for Indian cervical cancer patients treated by
indigenous modifications of the protocol are scarce. The objective of this
retrospective study was to analyze the efficacy and tolerability in patients of
cervical carcinoma treated by neoadjuvant chemotherapy followed by concurrent
chemoradiation. MATERIALS AND METHODS: Three hundred and thirty two cases of
squamous cell carcinoma of cervix who received 3 cycles of neoadjuvant
chemotherapy followed concurrent chemoradiation were retrospectively analyzed for
overall survival (OS), disease-free survival (DFS), and local pelvic control
rate. RESULTS: The 3-year OS and DFS were 93.7 % for stage I-B, 88.0 and 84.0 %
for stage II-A, 82.8 and 79.7 % for stage II-B, 70.0 and 64.9 % for stage III-A,
59.3 and 52.4 % for stage III-B, and 53.6 and 32.1 % for stage IV-A disease. The
5-year OS and DFS rates were 93.7 and 87.5 % for stage I-B, 84.0 % for Stage II
A, 79.7 and 76.6 % for stage II-B, 67.6 and 59.5 % for stage III-A, 48.4 and 41.9
% for stage III-B, and 28.6 and 14.3 % for stage IV-A disease. CONCLUSION:
Neoadjuvant chemotherapy followed by concurrent chemoradiation is feasible and
produces impressive disease-free and overall survival. This protocol is
especially helpful for busy cancer centers with long waiting lists on
radiotherapy machines.
PMID- 27486285
TI - Risks and Benefits of Total Laparoscopic Hysterectomy and the Effect of Learning
Curve on Them.
AB - STUDY OBJECTIVE: The objective of this study was to prospectively analyze the
risks and benefits of total laparoscopic hysterectomy (TLH) compared with total
abdominal hysterectomy (TAH) and the effects of learning curve on them over 4
years (March 2010-April 2014). DESIGN: It was a prospective randomized study.
SETTING: The study was conducted in Delhi government hospital which had no staff
with previous experience of advanced laparoscopic surgeries. PATIENTS: Two
hundred fifty patients were operated on for benign gynecological conditions (35
65 years). The numbers of cases operated laparoscopically were as follows-22 in
2010, 25 in 2011, 32 in 2012, and 46 in 2013. Equal number. of patients operated
by open surgery were taken in the study during the same time period. RESULTS: Two
hundred fifty cases were operated since March 2010, by either laparoscopic or
open surgery. Incidence of major complications was-1.6 % for TLH compared to 4 %
in TAH. After the first year of surgery, this incidence has fallen to 0 % in
subsequent years in TLH group. The incidence of minor complications declined from
14 to 4.5 % in the third year of study. Total rate of conversion to laparotomy
was 9.7 %, which again had a significant decline after the first year. TLH also
clearly showed superior benefits of less intraoperative blood loss, early
postoperative ambulance, and shorter period of hospital stay in comparison with
TAH. CONCLUSION: The study has led us to conclude that TLH is a safe, effective,
and reproducible technique after the completion of a period of training necessary
to standardize the procedure. This approach must be established in our real, day
to-day clinical practice.
PMID- 27486287
TI - Pulseless Disease in Pregnancy: A Rare Case.
PMID- 27486286
TI - Pros and Cons of Adding of Neoadjuvant Chemotherapy to Standard Concurrent
Chemoradiotherapy in Cervical Cancer: A Regional Cancer Center Experience.
AB - BACKGROUND: The present study summarizes the results of treatment in the form of
disease-free survival and overall survival in bulky stage IB2 and locally
advanced (stages II-IVA) squamous cell carcinoma of the uterine cervix. The
treatment has been given in the form of NACT followed by CCRT in one arm and CCRT
in the other arm. MATERIALS AND METHODS: This retrospective study analyzed 713
cervical cancer patients who were treated at our center during 2007 and 2008; out
of 713 patients, data of 612 patients have been compared. The patients' data were
analyzed retrospectively. Patients had undergone PF 28.6 %, TPF 21.5 %, and only
CCRT 49.9 %. Majority of patients were in the age group 41-50 years, while stage
wise, mainly stage IIIb and IIb. Disease-free survival was observed on the basis
of stage and NACT. The survival analyses were performed using the Kaplan-Meier
method. All statistical calculations were done with SPSS Statistics version 20.0.
RESULTS: For cancer cervix NACT versus CCRT, the DFS rate was at 5 years (58.3
vs. 41.8 % p = 0.001). NACT followed by CCRT demonstrated significantly superior
DFS as compared to definitive CCRT, respectively, TPF (hazard ratio (HR) = 0.248,
95 % confidence interval (CI) 0.123-0.500; p < 0.001), PF (HR = 0.445, 95 % CI
0.266-0.722; p = 0.002). The results of univariate stage, age, and multivariate
study show that stage hemoglobin level, interval between external-intracavitary
radiation, and type of neoadjuvant chemotherapy were the factors affected
survival cervical patients treated with radiation. The grade 3/4 hematologic
toxicities were more in the NACT group than CCRT (p < 0.001) while the non
hematological toxicity was not significant; the TPF group experienced more
toxicity than PF (p = 0.029). This treatment regimen is feasible as evidenced by
the acceptable toxicity of NACT and by the high compliance to radiotherapy. The
grade 3/4 hematologic toxicities were more in NACT groups than CCRT (p < 0.001);
the TPF group experienced more toxicity than PF (p = 0.029). CONCLUSION: TPF/PF
as NACT is feasible and produces impressive responses in cancer cervix.
PMID- 27486288
TI - Malignant Melanoma of Vagina: A Report and Review of Literature.
PMID- 27486289
TI - Clinical outcomes and prognostic factors depending on implant design in the
treatment of proximal humeral fractures: A retrospective study.
AB - PURPOSE: We aimed to examine the clinical outcomes of proximal humeral fractures
treated with different intramedullary nail shapes. METHODS: Thirty-seven patients
were divided into two groups depending on the implant shape. We also defined F
group as a subgroup of fracture classification. RESULTS: In the F group, the
flexion of the shoulder joint was significantly greater in S (mean, 134.6 degrees
) than in C groups (mean, 109 degrees ) (p = 0.04). The complication rate was
significantly larger in the C group (p = 0.04). CONCLUSIONS: Patients with one
kind of fracture and who were treated with straight nails had better outcomes.
PMID- 27486290
TI - Toxin yet not toxic: Botulinum toxin in dentistry.
AB - Paracelsus contrasted poisons from nonpoisons, stating that "All things are
poisons, and there is nothing that is harmless; the dose alone decides that
something is a poison". Living organisms, such as plants, animals, and
microorganisms, constitute a huge source of pharmaceutically useful medicines and
toxins. Depending on their source, toxins can be categorized as phytotoxins,
mycotoxins, or zootoxins, which include venoms and bacterial toxins. Any toxin
can be harmful or beneficial. Within the last 100 years, the perception of
botulinum neurotoxin (BTX) has evolved from that of a poison to a versatile
clinical agent with various uses. BTX plays a key role in the management of many
orofacial and dental disorders. Its indications are rapidly expanding, with
ongoing trials for further applications. However, despite its clinical use, what
BTX specifically does in each condition is still not clear. The main aim of this
review is to describe some of the unclear aspects of this potentially useful
agent, with a focus on the current research in dentistry.
PMID- 27486291
TI - Association between anterior alveolar dimensions and vertical facial pattern
among Saudi adults.
AB - OBJECTIVE: To establish the anterior alveolar dimensions among a sample of Saudi
subjects with different vertical facial heights. MATERIALS AND METHODS: Lateral
cephalometric radiographs of 63 Saudi subjects (30 males and 33 females) were
included in this retrospective study. The sample was divided into high angle (SN
MP ? 39 degrees ), low angle (SN-MP ? 28 degrees ) and average angle (30 degrees
< SN-MP < 37 degrees ) groups. The anteroposterior and vertical dimensions of the
alveolus surrounding the root apex of upper and lower incisors were calculated.
RESULTS: The anterior alveolar dimensions exhibited significant differences (p <
0.05) between the different vertical facial height groups. The males and females
demonstrated significant differences (p < 0.05) in the anterior alveolar
dimensions for the same vertical jaw relationship. CONCLUSIONS: Both gender and
the vertical jaw relationship can be factors for different height and thickness
of the anterior alveolus. Clinicians must be aware of differences in the anterior
alveolar dimensions for safe and sound orthodontic tooth movement.
PMID- 27486292
TI - Neurogenic tumors and tumor-like lesions of the oral and maxillofacial region: A
clinicopathological study.
AB - OBJECTIVE: Oral and maxillofacial lesions of neural origin are rare soft tissue
neoplasms. The aim of the present study is to review the epidemiological data of
oral and maxillofacial neurogenic lesions submitted for diagnosis to our
laboratory over a 31-year period (August 1984-March 2015). MATERIALS AND METHODS:
The available formalin-fixed embedded specimens, Hematoxylin and Eosin slides,
demographic and clinical data were retrieved. RESULTS: Thirty-one cases were
included in this study, representing 0.6% of the 5161 biopsies submitted. Most of
the diagnosed cases 11 (35.5%) were traumatic neuromas. The other cases included
2 (6.5%) solitary circumscribed neuromas, 2 (6.5%) melanotic neuroectodermal
tumors of infancy, 2 (6.5%) Schwannomas, 5 (16.1%) granular cell tumors, and 9
(29%) neurofibromas. The patients' ages ranged from 5 months to 78 years. Among
these cases, 16 were males (51.61%) and 15 were females (48.38%). CONCLUSION:
This analysis showed that neural lesions affecting the oral and maxillofacial
region were rare and mostly benign in nature. Such lesions should be carefully
diagnosed because of their association with life-threatening syndromes and the
possibility of malignant transformation.
PMID- 27486293
TI - A randomized control trial comparing the visual and verbal communication methods
for reducing fear and anxiety during tooth extraction.
AB - PURPOSE: To evaluate the value of using the visual information for reducing the
level of dental fear and anxiety in patients undergoing teeth extraction under
LA. METHODS: A total of 64 patients were indiscriminately allotted to solitary of
the study groups following reading the information sheet and signing the formal
consent. If patient was in the control group, only verbal information and routine
warnings were provided. If patient was in the study group, tooth extraction video
was showed. The level of dental fear and anxiety was detailed by the patients on
customary 100 mm visual analog scales (VAS), with "no dental fear and anxiety" (0
mm) and "severe dental distress and unease" (100 mm). Evaluation of dental
apprehension and fretfulness was made pre-operatively, following visual/verbal
information and post-extraction. RESULTS: There was a substantial variance among
the mean dental fear and anxiety scores for both groups post-extraction (p-value
< 0.05). Patients in tooth extraction video group were more comfortable after
dental extraction than verbal information and routine warning group. For tooth
extraction video group there were major decreases in dental distress and anxiety
scores between the pre-operative and either post video information scores or
postoperative scores (p-values < 0.05). Younger patients recorded higher dental
fear and anxiety scores than older ones (P < 0.05). CONCLUSION: Dental fear and
anxiety associated with dental extractions under local anesthesia can be reduced
by showing a tooth extraction video to the patients preoperatively.
PMID- 27486294
TI - A 22 year comparison survey of dental knowledge in Al-Jubail antenatal clinic
population.
AB - OBJECTIVE: To analyze and compare dental knowledge between two generations of
pregnant women attending the same antenatal clinic in Al-Jubail, Saudi Arabia.
METHODS: A cross sectional self administered questionnaire was conducted among
252 pregnant women in three different antenatal clinics. Data were analyzed using
SPSS (v. 21), p value <0.05 was considered statistically significant. RESULTS:
Most surveyed women were knowledgeable about dental health issues, although a
large percentage did not visit dental clinics regularly during pregnancy. Results
showed a decline in dental knowledge, compared with data collected 22 years ago.
Pregnant women participating in the current survey had more dental problems and
underwent more dental procedures than did those participating in the previous
survey. CONCLUSIONS: Results of this study show a decline in dental knowledge and
oral health in pregnant women of the current generation, compared with those of
the previous generation. Antenatal clinics should educate pregnant women more
about the relationship between good oral and fetal health.
PMID- 27486295
TI - Experimentation and correlates of electronic nicotine delivery system (electronic
cigarettes) among university students - A cross sectional study.
AB - OBJECTIVE: E-cigarettes are becoming popular among youth as safe nicotine
delivery systems. Many have expressed concern, however, that e-cigarettes may
serve as a gateway to future smoking, given their low perceived risk, or that
their use may prevent regular smokers from quitting by maintaining their nicotine
addiction. The aim of this study was to assess experimentation with and
correlates of e-cigarette use among university students. MATERIAL AND METHODS: A
cross-sectional study was carried out among 480 university students from four
faculties at a university in Riyadh in August-October 2014. A modified version of
the World Health Organization's Global Adult Tobacco Survey was used, and
multinomial logistic regression was carried out to assess correlations with e
cigarette variables in the whole study sample and among smokers. RESULTS: Almost
all students, including the majority of ex-smokers (96.3%) and smokers (94.4%),
reported having heard about e-cigarettes. In addition, about one-quarter of the
sample (54.2% of smokers, 24.7% of ex-smokers, 6% of never smokers) had
experimented with e-cigarettes at least once during their lifetime. Curiosity and
peer influence were reported as the main reasons for the use of e-cigarettes.
Factors found to be correlated significantly with e-cigarette use were male
gender, being a traditional cigarette smoker, having friends who have tried e
cigarettes, and having a strong belief that e-cigarettes could aid smoking
cessation. CONCLUSION: E-cigarettes are popular among Saudi youth, especially
among smokers and ex-smokers. Well-designed health education programs and
regulatory interventions are required to address this issue.
PMID- 27486297
TI - Notes on the Statistical Power of the Binary State Speciation and Extinction
(BiSSE) Model.
AB - The Binary State Speciation and Extinction (BiSSE) method is one of the most
popular tools for investigating the rates of diversification and character
evolution. Yet, based on previous simulation studies, it is commonly held that
the BiSSE method requires phylogenetic trees of fairly large sample sizes (>300
taxa) in order to distinguish between the different models of speciation,
extinction, or transition rate asymmetry. Here, the power of the BiSSE method is
reevaluated by simulating trees of both small and large sample sizes (30, 60, 90,
and 300 taxa) under various asymmetry models and root state assumptions. Results
show that the power of the BiSSE method can be much higher, also in trees of
small sample size, for detecting differences in speciation rate asymmetry than
anticipated earlier. This, however, is not a consequence of any conceptual or
mathematical flaw in the method per se but rather of assumptions about the
character state at the root of the simulated trees and thus the underlying
macroevolutionary model, which led to biased results and conclusions in earlier
power assessments. As such, these earlier simulation studies used to determine
the power of BiSSE were not incorrect but biased, leading to an overestimation of
type-II statistical error for detecting differences in speciation rate but not
for extinction and transition rates.
PMID- 27486296
TI - The range of diagnoses for oral soft-tissue biopsies of geriatric patients in a
Saudi Arabian teaching hospital.
AB - INTRODUCTION: The increased life expectancy being observed worldwide necessitates
careful planning for future geriatric oral health care needs, which should be
based on epidemiologic surveys to identify these needs. We aimed to survey the
range of lesions diagnosed in soft-tissue biopsies of patients over age 60 over a
30-year period in a Saudi Arabian teaching hospital. METHODS: The histopathology
records of geriatric patients with complete demographic data who were diagnosed
between 1984 and 2013 at the College of Dentistry, King Saud University, were
reviewed. The lesions were then classified into eight broad categories.
Associations between variables were evaluated using Pearson's Chi square test.
RESULTS: There were 231 soft-tissue biopsies obtained from geriatric patients
whose complete records were available. The male to female ratio was 1.1:1, and
the mean age was 66.7 years. Most lesions (69%) occurred in patents aged 60-69
years. Although reactive lesions were generally the most common, the most common
lesions were squamous cell carcinoma and fibroma. Lesions were most commonly
located on the buccal mucosa and the alveolar ridge/gingivae. CONCLUSIONS: The
range of lesions seen in Saudi geriatric patients were similar to those reported
for other parts of the world, although the lesions were more similar to those
reported from developing countries. The very high rate of oral cancer, however,
is expected to take the majority of the resources allocated to geriatric oral
health care, except if a strong, population-based prevention program is initiated
immediately.
PMID- 27486298
TI - Normalized lmQCM: An Algorithm for Detecting Weak Quasi-Cliques in Weighted Graph
with Applications in Gene Co-Expression Module Discovery in Cancers.
AB - In this paper, we present a new approach for mining weighted networks to identify
densely connected modules such as quasi-cliques. Quasi-cliques are densely
connected subnetworks in a network. Detecting quasi-cliques is an important topic
in data mining, with applications such as social network study and biomedicine.
Our approach has two major improvements upon previous work. The first is the use
of local maximum edges to initialize the search in order to avoid excessive
overlaps among the modules, thereby greatly reducing the computing time. The
second is the inclusion of a weight normalization procedure to enable discovery
of "subtle" modules with more balanced sizes. We carried out careful tests on
multiple parameters and settings using two large cancer datasets. This approach
allowed us to identify a large number of gene modules enriched in both biological
functions and chromosomal bands in cancer data, suggesting potential roles of
copy number variations (CNVs) involved in the cancer development. We then tested
the genes in selected modules with enriched chromosomal bands using The Cancer
Genome Atlas data, and the results strongly support our hypothesis that the
coexpression in these modules are associated with CNVs. While gene coexpression
network analyses have been widely adopted in disease studies, most of them focus
on the functional relationships of coexpressed genes. The relationship between
coexpression gene modules and CNVs are much less investigated despite the
potential advantage that we can infer from such relationship without genotyping
data. Our new approach thus provides a means to carry out deep mining of the gene
coexpression network to obtain both functional and genetic information from the
expression data.
PMID- 27486299
TI - Pathway-Informed Classification System (PICS) for Cancer Analysis Using Gene
Expression Data.
AB - We introduce Pathway-Informed Classification System (PICS) for classifying
cancers based on tumor sample gene expression levels. PICS is a computational
method capable of expeditiously elucidating both known and novel biological
pathway involvement specific to various cancers and uses that learned pathway
information to separate patients into distinct classes. The method clearly
separates a pan-cancer dataset by tissue of origin and also sub-classifies
individual cancer datasets into distinct survival classes. Gene expression values
are collapsed into pathway scores that reveal which biological activities are
most useful for clustering cancer cohorts into subtypes. Variants of the method
allow it to be used on datasets that do and do not contain noncancerous samples.
Activity levels of all types of pathways, broadly grouped into metabolic,
cellular processes and signaling, and immune system, are useful for separating
the pan-cancer cohort. In the clustering of specific cancer types, certain
pathway types become more valuable depending on the site being studied. For lung
cancer, signaling pathways dominate; for pancreatic cancer, signaling and
metabolic pathways dominate; and for melanoma, immune system pathways are the
most useful. This work suggests the utility of pathway-level genomic analysis and
points in the direction of using pathway classification for predicting the
efficacy and side effects of drugs and radiation.
PMID- 27486300
TI - Recursive Partitioning Method on Competing Risk Outcomes.
AB - In some cancer clinical studies, researchers have interests to explore the risk
factors associated with competing risk outcomes such as recurrence-free survival.
We develop a novel recursive partitioning framework on competing risk data for
both prognostic and predictive model constructions. We define specific splitting
rules, pruning algorithm, and final tree selection algorithm for the competing
risk tree models. This methodology is quite flexible that it can corporate both
semiparametric method using Cox proportional hazards model and parametric
competing risk model. Both prognostic and predictive tree models are developed to
adjust for potential confounding factors. Extensive simulations show that our
methods have well-controlled type I error and robust power performance. Finally,
we apply both Cox proportional hazards model and flexible parametric model for
prognostic tree development on a retrospective clinical study on oropharyngeal
cancer patients.
PMID- 27486301
TI - Transzonular vitreous injection vs a single drop compounded topical
pharmaceutical regimen after cataract surgery.
AB - PURPOSE: To compare the relative effectiveness of a Tri-Moxi-Vanc intraocular
solution injected transzonularly into the vitreous with the topical formulation
of Pred-Moxi-Ketor (given for the first week postoperatively) followed by Pred
Ketor (given for weeks 2-4 after surgery). PATIENTS AND METHODS: This was a
single-site, single-surgeon, prospective, randomized, subject-masked
contralateral eye study with an active comparator and was approved by an
appropriate ethics committee. Twenty-five subjects with uncomplicated cataract
who were scheduled for cataract surgery were enrolled. If surgery was uneventful,
subjects received either an injection in that eye or followed a minimum drop
postoperative pharmaceutical regimen. The second eye surgery was performed with
the opposite treatment. Subjects were followed for 1 month. Measures of interest
were the changes in intraocular pressure (IOP) from baseline and the changes in
corneal and macular thickness. Subjects were also asked to evaluate pain
perception, visual quality, and overall satisfaction with surgery. They were also
asked which regimen they preferred. RESULTS: IOP was not statistically
significantly different between the groups (P=0.81); there was also no
statistically significant difference in IOP over time (P=0.74). There was no
statistically significant difference in central macular thickness at 1 week and 1
month between the groups (P=0.18). The central corneal thickness was
significantly greater 1 day postoperatively relative to baseline, but there was
no statistically significant difference between the groups at any time point
(P=0.92). The difference in reported pain was also not statistically
significantly different between the groups (P=0.67). Satisfaction with surgery
was similar for both groups, but significantly more subjects preferred the
injection for overall experience (P<0.01). CONCLUSION: Cataract surgery completed
with the two pharmaceutical regimens was similar in outcome. Significantly more
subjects preferred the injection, presumably as a function of the greater
convenience with no apparent difference in the therapeutic effect.
PMID- 27486302
TI - Optical coherence tomography parameters predictive of visual outcome after anti
VEGF therapy for retinal vein occlusion.
AB - PURPOSE: To determine the optical coherence tomography (OCT) parameters that are
predictive of visual outcome after anti-VEGF therapy for a retinal vein occlusion
(RVO). METHODS: Fifty-seven eyes with macular edema (ME) secondary to a central
or branch RVO treated with bevacizumab or ranibizumab were studied. Spectral
domain OCT and microperimetry were performed before, 1, 3, and 6 months after the
treatment and at the final visit. Central retinal thickness (CRT), macular volume
(MV), integrity of the external limiting membrane (ELM), ellipsoid zone (EZ), and
foveal bulge (FB), and photoreceptor outer segment (PROS) length were determined.
RESULTS: The mean follow-up period was 17.8+/-11.5 months. In 46 of the 57 eyes,
a resolution of the ME was achieved. The pretreatment CRT and MV, presence of
intact ELM, EZ, and FB, and PROS length at the time of ME resolution were
significantly correlated with the best-corrected visual acuity and retinal
sensitivity at the final visit (P<0.050). Multiple regression analyses showed
that the pretreatment MV had the highest correlation with the posttreatment best
corrected visual acuity and retinal sensitivity (P<0.050). CONCLUSION: The CRT,
MV, ELM, EZ, FB, and PROS length are predictive factors for the visual outcome
after anti-VEGF therapy for RVO.
PMID- 27486303
TI - Inter-eye comparison of retinal oximetry and vessel caliber between eyes with
asymmetrical glaucoma severity in different glaucoma subtypes.
AB - BACKGROUND: To compare retinal vessel oxygenation and vessel caliber in primary
angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG), normal-tension
glaucoma (NTG), and normal controls, as well as between eyes of asymmetrical
glaucoma severity. METHODS: This was a prospective, cross-sectional study. The
159 subjects (PACG, n=39; POAG, n=41; NTG, n=41; normal controls, n=38) underwent
retinal oxygen saturation measurements using the Oxymap T1 Retinal Oximeter,
optical coherence tomography, and Humphrey visual field testing. Retinal oxygen
saturation and vessel diameter were compared between the glaucoma groups and
normal controls, as well as between eyes of asymmetrical glaucoma severity.
Kruskal-Wallis test was performed for comparison among different subtypes of
glaucoma. Wilcoxon signed-rank test was used to compare the inter-eye
differences. RESULTS: Compared to normal controls, arteriolar oxygen saturation
was increased in PACG eyes (P=0.048) but not in POAG or NTG eyes. There were no
significant differences in oxygen saturation in venules or arteriovenous (AV)
difference in all three glaucoma groups. Venular diameter was significantly
reduced in all glaucoma groups compared to normal controls (P<0.001), but no such
change was observed in arteriolar diameter (P=0.10). When comparing between eyes
of asymmetrical glaucoma severity, arteriolar oxygen saturation (P=0.03) and AV
difference (P=0.04) were significantly higher, while arteriolar diameter was
significantly lower (P=0.001) in the worse eye in PACG group. There were no
significant differences in oximetric parameters or vessel calibers between the
worse and the better eyes in POAG and NTG groups. CONCLUSION: Eyes with PACG
showed increased arteriolar oxygen saturation and increased AV difference. This
was not observed in POAG and NTG eyes. Arteriolar diameter in PACG and venular
diameter in all three glaucoma groups were reduced. The difference observed in
PACG eyes may be due to an increased metabolic demand in the disease process
compared to open-angle glaucoma.
PMID- 27486304
TI - Endothelial Nitric Oxide Synthase (-786T>C) and Endothelin-1 (5665G>T) Gene
Polymorphisms as Vascular Dysfunction Risk Factors in Sickle Cell Anemia.
AB - Sickle cell anemia (SCA) patients have vascular complications, and polymorphisms
in endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) genes were
associated with ET-1 and nitric oxide disturbance. We investigate the association
of ET-1 5665G>T and eNOS -786T>C polymorphisms with soluble adhesion molecules
(sVCAM-1 and sICAM-1), biochemical markers, and medical history. We studied 101
SCA patients; carriers of eNOS minor allele (C) had the highest levels of sVCAM
1, and carriers of ET-1 minor allele had more occurrence of acute chest syndrome
(ACS). The multivariate analysis suggested the influence of the ET-1 gene on ACS
outcome and an association of the eNOS gene with upper respiratory tract
infection. We suggest that eNOS and ET-1 gene polymorphisms can influence SCA
pathophysiology and that eNOS variant in SCA patients might be important to
nitric oxide activity and vascular alteration. We found an association of the ET
1 minor allele in ACS, showing the importance of genetic screening in SCA.
PMID- 27486305
TI - Sitagliptin/metformin fixed-dose combination in type 2 diabetes mellitus: an
evidence-based review of its place in therapy.
AB - Type 2 diabetes mellitus is a progressive disease associated with significant
morbidity and mortality. There is good evidence showing that intensive glycemic
control reduces the development and progression of complications. In order to
achieve glycemic targets, patients often require a combination of oral therapy
and/or insulin in addition to lifestyle modification. Unfortunately, many of the
traditional therapies for type 2 diabetes are associated with weight gain and
hypoglycemia, resulting in poor compliance and subsequent worsening of glycemic
control. The dipeptidyl peptidase-4 inhibitor sitagliptin is a therapy for type 2
diabetes and is available as a fixed-dose combination with metformin. Phase III
clinical trials have demonstrated beneficial effects on glycemic control and
minimal untoward effects with this combination. In this article, we provide an
overview of the pharmacology, efficacy, and safety and examine the role of this
combination within current practice.
PMID- 27486307
TI - Rational design and synthesis of novel diphenyl ether derivatives as
antitubercular agents.
AB - A series of triclosan mimic diphenyl ether derivatives have been synthesized and
evaluated for their in vitro antitubercular activity against Mycobacterium
tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl
acyl carrier protein reductase of M. tuberculosis has been explored. Among them,
compound 10b was found to possess antitubercular activity (minimum inhibitory
concentration =12.5 ug/mL) comparable to triclosan. All the synthesized compounds
exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three
compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b
was also evaluated for log P, pKa, human liver microsomal stability, and %
protein binding, in order to probe its druglikeness. Based on the antitubercular
activity and druglikeness profile, it may be concluded that compound 10b could be
a lead for future development of antitubercular drugs.
PMID- 27486306
TI - Galeterone for the treatment of advanced prostate cancer: the evidence to date.
AB - Major advances have been achieved recently in the treatment of metastatic
castration-resistant prostate cancer, resulting in significant improvements in
quality of life and survival with the use of several new agents, including the
next-generation androgen receptor (AR)-targeted drugs abiraterone and
enzalutamide. However, virtually all patients will eventually progress on these
therapies and most will ultimately die of treatment-refractory metastatic
disease. Recently, several mechanisms of resistance to AR-directed therapies have
been uncovered, including the AR splice variant 7 (AR-V7), which is a ligand
independent constitutionally-active form of the AR that has been associated with
poor outcomes to abiraterone and enzalutamide. Galeterone, a potent anti-androgen
with three modes of action (CYP17 lyase inhibition, AR antagonism, and AR
degradation), is a novel agent under clinical development that could potentially
target both full-length AR and aberrant AR, including AR-V7. In this manuscript,
we will first discuss the biological mechanisms of action of galeterone and then
review the safety and efficacy data from Phase I and II clinical studies of
galeterone in patients with metastatic castration-resistant prostate cancer. A
Phase III study of galeterone (compared against enzalutamide) in AR-V7-positive
patients is currently underway, and represents the first pivotal trial using a
biomarker-selection design in this disease.
PMID- 27486308
TI - SPOCK1 promotes tumor growth and metastasis in human prostate cancer.
AB - Prostate cancer is the most diagnosed noncutaneous cancer and ranks as the second
leading cause of cancer-related deaths in American males. Metastasis is the
primary cause of prostate cancer mortality. Survival rate is only 28% for
metastatic patients, but is nearly 100% for patients with localized prostate
cancers. Molecular mechanisms that underlie this malignancy remain obscure, and
this study investigated the role of SPARC/osteonectin, cwcv, and kazal-like
domain proteoglycan 1 (SPOCK1) in prostate cancer progression. Initially, we
found that SPOCK1 expression was significantly higher in prostate cancer tissues
relative to noncancerous tissues. In particular, SPOCK1 expression was also
markedly high in metastatic tissues compared with nonmetastatic cancerous
tissues. SPOCK1 expression knockdown by specific short hairpin RNA in PC3 cells
was significantly inhibited, whereas SPOCK1 overexpression in RWPE-1 cells
promoted cell viability, colony formation in vitro, and tumor growth in vivo.
Moreover, the SPOCK1 knockdown in PC3 cells was associated with cell cycle arrest
in G0/G1 phase, while the SPOCK1 overexpression in RWPE-1 cells induced cell
cycle arrest in S phase. The SPOCK1 knockdown in PC3 cells even increased cell
apoptosis. SPOCK1 modulation was also observed to affect cancerous cell
proliferation and apoptotic processes in the mouse model of prostate cancer.
Additionally, the SPOCK1 knockdown decreased, whereas the SPOCK1 overexpression
increased cell migration and invasion abilities in vitro. Injection of SPOCK1
depleted PC3 cells significantly decreased metastatic nodules in mouse lungs.
These findings suggest that SPOCK1 is a critical mediator of tumor growth and
metastasis in prostate cancer.
PMID- 27486309
TI - Prediction of selective estrogen receptor beta agonist using open data and
machine learning approach.
AB - BACKGROUND: Estrogen receptors (ERs) are nuclear transcription factors that are
involved in the regulation of many complex physiological processes in humans. ERs
have been validated as important drug targets for the treatment of various
diseases, including breast cancer, ovarian cancer, osteoporosis, and
cardiovascular disease. ERs have two subtypes, ER-alpha and ER-beta. Emerging
data suggest that the development of subtype-selective ligands that specifically
target ER-beta could be a more optimal approach to elicit beneficial estrogen
like activities and reduce side effects. METHODS: Herein, we focused on ER-beta
and developed its in silico quantitative structure-activity relationship models
using machine learning (ML) methods. RESULTS: The chemical structures and ER-beta
bioactivity data were extracted from public chemogenomics databases. Four types
of popular fingerprint generation methods including MACCS fingerprint, PubChem
fingerprint, 2D atom pairs, and Chemistry Development Kit extended fingerprint
were used as descriptors. Four ML methods including Naive Bayesian classifier, k
nearest neighbor, random forest, and support vector machine were used to train
the models. The range of classification accuracies was 77.10% to 88.34%, and the
range of area under the ROC (receiver operating characteristic) curve values was
0.8151 to 0.9475, evaluated by the 5-fold cross-validation. Comparison analysis
suggests that both the random forest and the support vector machine are superior
for the classification of selective ER-beta agonists. Chemistry Development Kit
extended fingerprints and MACCS fingerprint performed better in structural
representation between active and inactive agonists. CONCLUSION: These results
demonstrate that combining the fingerprint and ML approaches leads to robust ER
beta agonist prediction models, which are potentially applicable to the
identification of selective ER-beta agonists.
PMID- 27486310
TI - Voiding dysfunction in patients with nasal congestion treated with
pseudoephedrine: a prospective study.
AB - BACKGROUND: Pseudoephedrine is a sympathomimetic drug widely used as a nasal
decongestant. However, it can cause adverse effects, such as voiding dysfunction.
The risk of voiding dysfunction remains uncertain in patients without subjective
voiding problems. METHODOLOGY: We prospectively enrolled patients with nasal
congestion who required treatment with pseudoephedrine from May to August 2015.
All patients denied concomitant subjective voiding problem. The International
Prostate Symptom Score (IPSS) questionnaire was used to evaluate voiding function
before and 1 week after the pseudoephedrine treatment. The results of the IPSS
questionnaire were analyzed as the total (IPSS-T), voiding (IPSS-V), storage
(IPSS-S), and quality of life due to urinary symptom scores. RESULTS: We enrolled
131 males with a mean age of 42.0+/-14.3 years. The IPSS-T, IPSS-V, and IPSS-S
scores slightly increased after the medication (IPSS-T increased from 6.49 to
6.77, IPSS-V from 3.33 to 3.53, and IPSS-S from 3.17 to 3.24). The quality of
life due to urinary symptom score nonsignificantly decreased from 2.02 to 1.87.
We observed that older age and a higher premedication IPSS-V score yielded
significant differences (P<0.05) for subclinical voiding dysfunction and
unchanged voiding function. In patients aged >=50 years, the IPSS-T, IPSS-V, and
IPSS-S scores significantly increased after the pseudoephedrine treatment (IPSS-T
increased from 9.95 to 11.45, IPSS-V from 5.38 to 6.07, and IPSS-S 4.57 to 5.38),
whereas the quality of life due to urinary symptom score nonsignificantly
decreased from 2.71 to 2.48 (P=0.057). In patients aged <50 years, all scores did
not significantly differ. CONCLUSION: Pseudoephedrine treatment for nasal
congestion requires extra precautions in males >50 years, even without subjective
voiding symptoms.
PMID- 27486311
TI - Simultaneous surgery in patients with both cardiac and noncardiac diseases.
AB - BACKGROUND: To investigate the possibility and feasibility of simultaneous
cardiac and noncardiac surgery. METHODS: From August 2000 to March 2015, 64
patients suffering from cardiac and noncardiac diseases have been treated by
simultaneous surgeries. RESULTS: Two patients died after operations in hospital;
thus, the hospital mortality rate was 3.1%. One patient with coronary heart
disease, acute myocardial infarction, and a recurrence of bladder cancer accepted
emergency simultaneous coronary artery bypass grafting (CABG), bladder
cystectomy, and ureterostomy. He died of acute cerebral infarction complicated
with multiple organ failure on the 153rd day after operation. The other patient
with chronic constrictive pericarditis and right lung cancer underwent
pericardial stripping and right lung lower lobectomy, which resulted in multiple
organ failure, and the patient died on the tenth day postoperatively. The
remaining 62 patients recovered and were discharged. The total operative
morbidity was 17.2%: postoperative hemorrhage (n, % [1, 1.6%]), pulmonary
infection and hypoxemia (2, 3.1%), hemorrhage of upper digestive tract (1, 1.6%),
incisional infection (3, 4.7%), subphrenic abscess (1, 1.6%), and postoperative
acute renal failure and hemofiltration (3, 4.7%). Of the 62 patients discharged,
61 patients were followed up. Eleven patients died with 10 months to 10 years
during the follow-up. The mean survival time is 116.2+/-12.4 months. The
cumulative survival rate is 50.8%. CONCLUSION: Simultaneous surgeries in patients
suffering from both cardiac and noncardiac benign or malignant diseases are safe
and possible with satisfactory short-term and long-term survival.
PMID- 27486312
TI - Cardiovascular risk prediction: a comparative study of Framingham and quantum
neural network based approach.
AB - PURPOSE: Currently cardiovascular diseases (CVDs) are the main cause of death
worldwide. Disease risk estimates can be used as prognostic information and
support for treating CVDs. The commonly used Framingham risk score (FRS) for CVD
prediction is outdated for the modern population, so FRS may not be accurate
enough. In this paper, a novel CVD prediction system based on machine learning is
proposed. METHODS: This study has been conducted with the data of 689 patients
showing symptoms of CVD. Furthermore, the dataset of 5,209 CVD patients of the
famous Framingham study has been used for validation purposes. Each patient's
parameters have been analyzed by physicians in order to make a diagnosis. The
proposed system uses the quantum neural network for machine learning. This system
learns and recognizes the pattern of CVD. The proposed system has been
experimentally evaluated and compared with FRS. RESULTS: During testing,
patients' data in combination with the doctors' diagnosis (predictions) are used
for evaluation and validation. The proposed system achieved 98.57% accuracy in
predicting the CVD risk. The CVD risk predictions by the proposed system, using
the dataset of the Framingham study, confirmed the potential risk of death,
deaths which actually occurred and had been recorded as due to myocardial
infarction and coronary heart disease in the dataset of the Framingham study. The
accuracy of the proposed system is significantly higher than FRS and other
existing approaches. CONCLUSION: The proposed system will serve as an excellent
tool for a medical practitioner in predicting the risk of CVD. This system will
be serving as an aid to medical practitioners for planning better medication and
treatment strategies. An early diagnosis may be effectively made by using this
system. An overall accuracy of 98.57% has been achieved in predicting the risk
level. The accuracy is considerably higher compared to the other existing
approaches. Thus, this system must be used instead of the well-known FRS.
PMID- 27486313
TI - A role of ZnO nanoparticle electrostatic properties in cancer cell cytotoxicity.
AB - ZnO nanoparticles (NPs) have previously been shown to exhibit selective
cytotoxicity against certain types of cancerous cells suggesting their potential
use in biomedical applications. In this study, we investigate the effect of
surface modification of ZnO NPs on their cytotoxicity to both cancerous and
primary T cells. Our results show that polyacrylic acid capping produces
negatively charged ZnO NPs that are significantly more toxic compared to uncapped
positively charged NPs of identical size and composition. In contrast, the
greatest selectivity against cancerous cells relative to normal cells is observed
with cationic NPs. In addition, differences in NP cytotoxicity inversely
correlate with NP hydrodynamic size, propensity for aggregation, and dissolution
profiles. The generation of reactive oxygen species (ROS) was also observed in
the toxicity mechanism with anionic NPs generating higher levels of mitochondrial
superoxide without appreciably affecting glutathione levels. Additional
experiments evaluated the combined effects of charged ZnO NPs and nontoxic
cationic or anionic CeO2 NPs. Results show that the CeO2 NPs offer protective
effects against cytotoxicity from anionic ZnO NPs via antioxidant properties.
Altogether, study data indicate that surface modification of NPs and resulting
changes in their surface charge affect the level of intracellular ROS production,
which can be ameliorated by the CeO2 ROS scavenger, suggesting that ROS
generation is a dominant mechanism of ZnO NP cytotoxicity. These findings
demonstrate the importance of surface electrostatic properties for controlling NP
toxicity and illustrate an approach for engineering NPs with desired properties
for potential use in biological applications.
PMID- 27486314
TI - Phylogenetic and Structural Analysis of the Pluripotency Factor Sex-Determining
Region Y box2 Gene of Camelus dromedarius (cSox2).
AB - Although the sequencing information of Sox2 cDNA for many mammalian is available,
the Sox2 cDNA of Camelus dromedaries has not yet been characterized. The
objective of this study was to sequence and characterize Sox2 cDNA from the brain
of C. dromedarius (also known as Arabian camel). A full coding sequence of the
Sox2 gene from the brain of C. dromedarius was amplified by reverse transcription
PCRjmc and then sequenced using the 3730XL series platform Sequencer (Applied
Biosystem) for the first time. The cDNA sequence displayed an open reading frame
of 822 nucleotides, encoding a protein of 273 amino acids. The molecular weight
and the isoelectric point of the translated protein were calculated as 29.825 kDa
and 10.11, respectively, using bioinformatics analysis. The predicted cSox2
protein sequence exhibited high identity: 99% for Homo sapiens, Mus musculus, Bos
taurus, and Vicugna pacos; 98% for Sus scrofa and 93% for Camelus ferus. A 3D
structure was built based on the available crystal structure of the HMG-box
domain of human stem cell transcription factor Sox2 (PDB: 2 LE4) with 81 residues
and predicting bioinformatics software for 273 amino acid residues. The
comparison confirms the presence of the HMG-box domain in the cSox2 protein. The
orthologous phylogenetic analysis showed that the Sox2 isoform from C.
dromedarius was grouped with humans, alpacas, cattle, and pigs. We believe that
this genetic and structural information will be a helpful source for the
annotation. Furthermore, Sox2 is one of the transcription factors that
contributes to the generation-induced pluripotent stem cells (iPSCs), which in
turn will probably help generate camel induced pluripotent stem cells (CiPSCs).
PMID- 27486315
TI - Daily home gardening improved survival for older people with mobility
limitations: an 11-year follow-up study in Taiwan.
AB - AIMS: To test the hypothesis that gardening is beneficial for survival after
taking time-dependent comorbidities, mobility, and depression into account in a
longitudinal middle-aged (50-64 years) and older (>=65 years) cohort in Taiwan.
METHODS: The cohort contained 5,058 nationally sampled adults >=50 years old from
the Taiwan Longitudinal Study on Aging (1996-2007). Gardening was defined as
growing flowers, gardening, or cultivating potted plants for pleasure with five
different frequencies. We calculated hazard ratios for the mortality risks of
gardening and adjusted the analysis for socioeconomic status, health behaviors
and conditions, depression, mobility limitations, and comorbidities. Survival
models also examined time-dependent effects and risks in each stratum contingent
upon baseline mobility and depression. Sensitivity analyses used imputation
methods for missing values. RESULTS: Daily home gardening was associated with a
high survival rate (hazard ratio: 0.82; 95% confidence interval: 0.71-0.94). The
benefits were robust for those with mobility limitations, but without depression
at baseline (hazard ratio: 0.64, 95% confidence interval: 0.48-0.87) when
adjusted for time-dependent comorbidities, mobility limitations, and depression.
Chronic or relapsed depression weakened the protection of gardening. For those
without mobility limitations and not depressed at baseline, gardening had no
effect. Sensitivity analyses using different imputation methods yielded similar
results and corroborated the hypothesis. CONCLUSION: Daily gardening for pleasure
was associated with reduced mortality for Taiwanese >50 years old with mobility
limitations but without depression.
PMID- 27486316
TI - Predicting Gleason score using the initial serum total prostate-specific antigen
in Black men with symptomatic prostate adenocarcinoma in Nigeria.
AB - BACKGROUND: Men of Black African descent are known to have the highest incidence
of prostate cancer. The disease is also more aggressive in this group possibly
due to biologically more aggressive tumor or late presentation. Currently, serum
prostate-specific antigen (PSA) assay plays a significant role in making the
diagnosis of prostate cancer. However, the obtained value of serum PSA may not
directly relate with the Gleason score (GS), a measure of tumor aggression in
prostate cancer. This study explores the relationship between serum total PSA at
presentation (iPSA) and GS. PATIENTS AND METHODS: The iPSA of patients with
histologically confirmed prostate cancer was compared with the obtained GS of the
prostate biopsy specimens. The age of the patients at presentation and the
prostate volumes were also analyzed with respect to the iPSA and GS. The data
were analyzed retrospectively using IBM SPSS Version 20. Pearson correlation was
used for numeric variables, whereas Fisher's exact test was used for categorical
variables. Significance was set at P<=0.05. RESULTS: There were 205 patients from
January 2010 to November 2013 who satisfied the inclusion criteria. iPSA as well
as age at presentation and prostate volume were not found to significantly
correlate with the primary Gleason grade, the secondary Gleason grade, or the GS.
However, the presence of distant metastasis was identified to significantly
correlate positively with GS. CONCLUSION: GS may not be confidently predicted by
the iPSA. Higher iPSA does not correlate with higher GS and vice versa.
PMID- 27486317
TI - Colorectal cancer development and advances in screening.
AB - Most colon tumors develop via a multistep process involving a series of
histological, morphological, and genetic changes that accumulate over time. This
has allowed for screening and detection of early-stage precancerous polyps before
they become cancerous in individuals at average risk for colorectal cancer (CRC),
which may lead to substantial decreases in the incidence of CRC. Despite the
known benefits of early screening, CRC remains the second leading cause of cancer
related deaths in the United States. Hence, it is important for health care
providers to have an understanding of the risk factors for CRC and various stages
of disease development in order to recommend appropriate screening strategies.
This article provides an overview of the histological/molecular changes that
characterize the development of CRC. It describes the available CRC screening
methods and their advantages and limitations and highlights the stages of CRC
development in which each screening method is most effective.
PMID- 27486318
TI - Effects of biomass smoke on pulmonary functions: a case control study.
AB - BACKGROUND: Biomass smoke is the leading cause of COPD in developing countries
such as Turkey. In rural areas of Turkey, females are more exposed to biomass
smoke because of traditional lifestyles. AIM: The aim of this study was to
determine the adverse effects of biomass smoke on pulmonary functions and define
the relationship between duration in years and an index (cumulative exposure
index) with altered pulmonary function test results. PARTICIPANTS AND METHODS: A
total of 115 females who lived in the village of Kagizman (a borough of Kars
located in the eastern part of Turkey) and were exposed to biomass smoke were
included in the study. The control group was generated with 73 individuals living
in the same area who were never exposed to biomass smoke. RESULTS: Twenty-seven
(23.8%) females in the study group and four (5.5%) in the control group had small
airway disease (P=0.038). Twenty-two (19.1%) females in the study group and ten
(13.7%) in the control group had obstruction (P=0.223). Twenty (17.3%) females in
the study group who were exposed to biomass smoke had restriction compared with
ten (13%) in the control group (P=0.189). The duration needed for the existence
of small airway disease was 16 years, for obstructive airway disease was 17
years, and for restrictive airway disease was 17 years. The intensity of biomass
smoke was defined in terms of cumulative exposure index; it was calculated by
multiplying hours per day, weeks per month, and total years of smoke exposure and
dividing the result by three. CONCLUSION: Exposure to biomass smoke is a serious
public health problem, especially in rural areas of developing countries, because
of its negative effects on pulmonary functions. As the duration and the intensity
of exposure increase, the probability of having altered pulmonary function test
results is higher.
PMID- 27486319
TI - Increased cutaneous wound healing effect of biodegradable liposomes containing
madecassoside: preparation optimization, in vitro dermal permeation, and in vivo
bioevaluation.
AB - Madecassoside (MA) is highly potent in treating skin disorders such as wounds and
psoriasis. However, the topical wound healing effect of MA was hampered by its
poor membrane permeability. In order to overcome this shortcoming, MA liposomes
were designed and prepared by a double-emulsion method to enhance transdermal and
wound healing effects. In this study, response surface methodology was adopted to
yield the optimal preparation conditions of MA double-emulsion liposomes with
average particle size of 151 nm and encapsulation efficiency of 70.14%. Moreover,
MA double-emulsion liposomes demonstrated superior stability and homogeneous
appearance in 5 months; their leakage rate was <12% even at 37 degrees C and <5%
at 4 degrees C within 1 month. In vitro skin permeation, skin distribution, and
burn wound healing of MA liposomal formulations were conducted for the first time
to evaluate MA delivery efficiency and wound healing effect. The transdermal
property and wound cure effect of MA double-emulsion liposomes were superior to
those of MA film dispersion liposomes, and both the methods were endowed with an
excellent performance by polyethylene glycol modification. In conclusion, double
emulsion liposome formulation was an applicable and promising pharmaceutical
preparation for enhancing MA delivery toward wound healing effect and improving
wound-healing progress.
PMID- 27486320
TI - Cerium oxide nanoparticles inhibit the migration and proliferation of gastric
cancer by increasing DHX15 expression.
AB - Gastric cancer is one of the leading causes of tumor-related deaths in the world.
Current treatment options do not satisfy doctors and patients, and new therapies
are therefore needed. Cerium oxide nanoparticles (CNPs) have been studied as a
potential therapeutic approach for treating many diseases. However, their effects
on human gastric cancer are currently unknown. Therefore, in this study, we aimed
to characterize the effects of CNPs on human gastric cancer cell lines (MKN28 and
BGC823). Gastric cancer cells were cocultured with different concentrations of
CNPs, and proliferation and migration were measured both in vitro and in vivo. We
found that CNPs inhibited the migration of gastric cancer cells when applied at
different concentrations, but only a relatively high concentration (10 ug/mL) of
CNPs suppressed proliferation. Furthermore, we found that CNPs increased the
expression of DHX15 and its downstream signaling pathways. We therefore provide
evidence showing that CNPs may be a promising approach to suppress malignant
activity of gastric cancer by increasing the expression of DHX15.
PMID- 27486322
TI - Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc
aluminum-layered double hydroxide based nanocomposites.
AB - The chemotherapy for tuberculosis (TB) is complicated by its long-term treatment,
its frequent drug dosing, and the adverse effects of anti-TB drugs. In this
study, we have developed two nanocomposites (A and B) by intercalating the anti
TB drug isoniazid (INH) into Zn/Al-layered double hydroxides. The average size of
the nanocomposites was found to be164 nm. The efficacy of the Zn/Al-layered
double hydroxides intercalated INH against Mycobacterium tuberculosis was
increased by approximately three times more than free INH. The nanocomposites
were also found to be active against Gram-positive and -negative bacteria.
Compared to the free INH, the nanodelivery formulation was determined to be three
times more biocompatible with human normal lung fibroblast MRC-5 cells and 3T3
fibroblast cells at a very high concentration of 50 ug/mL for up to 72 hours. The
in vitro release of INH from the Zn/Al-layered double hydroxides was found to be
sustained in human body-simulated buffer solutions of pH 4.8 and 7.4. This
research is a step forward in making the TB chemotherapy patient friendly.
PMID- 27486321
TI - Remote magnetic targeting of iron oxide nanoparticles for cardiovascular
diagnosis and therapeutic drug delivery: where are we now?
AB - Magnetic resonance imaging (MRI) allows for an accurate assessment of both
functional and structural cardiac parameters, and thereby appropriate diagnosis
and validation of cardiovascular diseases. The diagnostic yield of cardiovascular
MRI examinations is often increased by the use of contrast agents that are almost
exclusively based on gadolinium compounds. Another clinically approved contrast
medium is composed of superparamagnetic iron oxide nanoparticles (IONs). These
particles may expand the field of contrast-enhanced cardiovascular MRI as
recently shown in clinical studies focusing on acute myocardial infarction (AMI)
and atherosclerosis. Furthermore, IONs open up new research opportunities such as
remote magnetic drug targeting (MDT). The approach of MDT relies on the coupling
of bioactive molecules and magnetic nanoparticles to form an injectable complex.
This complex, in turn, can be attracted to and retained at a desired target
inside the body with the help of applied magnetic fields. In comparison to common
systemic drug applications, MDT techniques promise both higher concentrations at
the target site and lower concentrations elsewhere in the body. Moreover,
concurrent or subsequent MRI can be used for noninvasive monitoring of drug
distribution and successful delivery to the desired organ in vivo. This review
does not only illustrate the basic conceptual and biophysical principles of IONs,
but also focuses on new research activities and achievements in the
cardiovascular field, mainly in the management of AMI. Based on the presentation
of successful MDT applications in preclinical models of AMI, novel approaches and
the translational potential of MDT are discussed.
PMID- 27486323
TI - Annonaceous acetogenins nanosuspensions stabilized by PCL-PEG block polymer:
significantly improved antitumor efficacy.
AB - Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a
variety of cancer cell lines, but their clinical application has been limited by
their poor solubility. In this study, ACGs-nanosuspensions (NSps) were
successfully prepared by a precipitation ultrasonic method using monomethoxypoly
(ethylene glycol)2000-poly (epsilon-caprolactone)2000 (mPEG2000-PCL2000) as a
stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta
potential of -20.17 mV, and a high drug payload of 73.68%. ACGs-NSps were quite
stable in various physiological solutions, and they exhibited sustained drug
release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against
4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation
after labeling with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, a
noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could
effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor
bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy
than the traditional dosage form (oil solution) even at 1/10 of the dose (74.83%
vs 45.53%, P<0.05), demonstrating that NSp was a good dosage form for ACGs to
treat cancer.
PMID- 27486324
TI - Controlled release hydrogen sulfide delivery system based on mesoporous silica
nanoparticles protects graft endothelium from ischemia-reperfusion injury.
AB - Hydrogen sulfide (H2S) functions as a protective gas transmitter in various
physiological and pathological processes, but the lack of ideal donors severely
hampers the clinical application of H2S. This study aims to construct a
controlled release H2S donor and evaluate its protective effect on graft
endothelium. Mesoporous silica nanoparticles (MSNs) were synthesized using the
sol-gel method and loaded with diallyl trisulfide (DATS), an H2S-releasing agent
named DATS-MSN. In vitro experiments showed that DATS-MSN could alleviate
endothelial cell inflammation and enhance endothelial cell proliferation and
migration. In vivo experiments demonstrated that the apoptosis of graft
endothelium was mitigated in the presence of DATS-MSN. Our results indicated that
DATS-MSN, releasing H2S in a controlled release fashion, could serve as an ideal
H2S donor.
PMID- 27486325
TI - A clinician's guide to recurrent isolated sleep paralysis.
AB - This review summarizes the empirical and clinical literature on sleep paralysis
most relevant to practitioners. During episodes of sleep paralysis, the sufferer
awakens to rapid eye movement sleep-based atonia combined with conscious
awareness. This is usually a frightening event often accompanied by vivid, waking
dreams (ie, hallucinations). When sleep paralysis occurs independently of
narcolepsy and other medical conditions, it is termed "isolated" sleep paralysis.
Although the more specific diagnostic syndrome of "recurrent isolated sleep
paralysis" is a recognized sleep-wake disorder, it is not widely known to
nonsleep specialists. This is likely due to the unusual nature of the condition,
patient reluctance to disclose episodes for fear of embarrassment, and a lack of
training during medical residencies and graduate education. In fact, a growing
literature base has accrued on the prevalence, risk factors, and clinical impact
of this condition, and a number of assessment instruments are currently available
in both self-report and interview formats. After discussing these and providing
suggestions for accurate diagnosis, differential diagnosis, and patient
selection, the available treatment options are discussed. These consist of both
pharmacological and psychotherapeutic interventions which, although promising,
require more empirical support and larger, well-controlled trials.
PMID- 27486326
TI - Parenting, identity development, internalizing symptoms, and alcohol use: a cross
sectional study in a group of Italian adolescents.
AB - BACKGROUND: Literature has demonstrated the adaptive function of identity
development and parenting toward manifestation of problem behaviors in
adolescence. These dimensions act on both internalizing and externalizing
symptoms. METHODS: The objective is to investigate the relationship between
identity status, parenting, and adolescent problems, which may manifest through
internalized (phobias, obsessions, depression, eating disorders, entropy) and
externalized modes (alcohol use and school discomfort). The research involved 198
Italian students (104 males and 94 females) in the 4th year (mean =16.94 years,
standard deviation =0.35) and 5th year (mean =17.94 years, standard deviation
=0.43) of senior secondary schools, who live in Caltanissetta, a town located in
Sicily, Italy. The research lasted for 1 school year. The general group consisted
of 225 students with a mortality rate of 12%. They completed an anamnestic
questionnaire to provide 1) basic information, 2) alcohol consumption attitude in
the past 30 days, and 3) their beliefs about alcohol; the "Ego Identity Process
Questionnaire" to investigate identity development; the "Parental Bonding
Instrument" to measure the perception of parenting during childhood; and the
"Constraints of Mind" to value the presence of internalizing symptoms. RESULTS:
Data show that identity status influences alcohol consumption. Low-profile
identity and excessive maternal control affect the relational dependence and the
tendency to perfectionism in adolescents. Among the predictors of alcohol use,
there are socioeconomic status, parental control, and the presence of
internalizing symptoms. CONCLUSION: Family is the favored context of learning
beliefs, patterns, and values that affect the broader regulatory social
environment, and for this reason, it is considered the privileged context on
which to intervene to reduce the adolescents' behavior problems. This deviance
could be an external manifestation of the difficulty in management of
internalizing symptoms in adolescence.
PMID- 27486327
TI - Association of brain-derived neurotrophic factor and nerve growth factor gene
polymorphisms with susceptibility to migraine.
AB - Migraine is one of the most common neurological diseases worldwide. Migraine
pathophysiology is very complex. Genetic factors play a major role in migraine.
Neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve
growth factor (NGF), play an important role in central nervous system
functioning, development, and modulation of pain. This study investigates whether
polymorphisms in the BDNF and NGF genes are associated with migraine disease in a
Turkish case-control population. Overall, 576 subjects were investigated (288
patients with migraine and 288 healthy controls) for the following polymorphisms:
rs6265(G/A), rs8192466(C/T), rs925946(G/T), rs2049046(A/T), and rs12273363(T/C)
in the BDNF gene, and rs6330(C/T), rs11466112(C/T), rs11102930(C/A), and
rs4839435(G/A) in the NGF gene using 5'-exonuclease allelic discrimination
assays. We found no differences in frequency of the analyzed eight polymorphisms
between migraine and control groups. However, the frequency of minor A alleles of
rs6265 in BDNF gene was borderline significant in the patients compared with the
healthy controls (P=0.049; odds ratios [ORs] [95% confidence intervals {CIs}]
=0.723 [0.523-0.999]). Moreover, when the migraine patients were divided into two
subgroups, migraine with aura (MA) and migraine without aura (MO), the minor TT
genotype of rs6330 in NGF was significantly higher in MA patients than in MO
patients (P=0.036) or healthy controls (P=0.026), and this disappeared after
correction for multiple testing. Also, the rs6330*T minor allele was more common
in the MA group than in the MO group or controls (P=0.011, ORs [95% CIs] =1.626
[1.117-2.365] or P=0.007, ORs [95% CIs] =1.610 [1.140-2.274], respectively). In
conclusion, this is the first clinical study to evaluate the association between
BDNF and NGF polymorphisms in migraine patients compared with health controls.
Our findings suggest that the NGF rs6330*T minor allele might be nominated as a
risk factor for developing aura in migraine disease. Our results should be
considered as preliminary, and they need to be confirmed by future studies.
PMID- 27486328
TI - An overview of the effect of sodium glucose cotransporter 2 inhibitor monotherapy
on glycemic and other clinical laboratory parameters in type 2 diabetes patients.
AB - OBJECTIVES: We aimed to determine the effect of sodium glucose cotransporter 2
(SGLT2) inhibitor monotherapy on glycemic and other clinical laboratory
parameters versus other antidiabetic medications or placebo therapy in patients
with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of
diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its
weight-sparing ability. DESIGN: Meta-analysis. MATERIALS AND METHODS: PubMed and
MEDLINE were searched to identify eligible studies up to December 2015.
Randomized controlled trials that assessed the efficacy and safety of SGLT2
inhibitor monotherapy versus placebo therapy or active control were considered.
The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and
bias. The mean difference was used to evaluate the glycemic and other clinical
laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or
placebo. Similarly, the risk ratio was used to assess adverse events, and the I
(2) was used to evaluate heterogeneity. RESULTS: SGLT2 inhibitors significantly
decreased glycated hemoglobin (HbA1c) (P<0.001), weight (P<0.001), and the low
density lipoprotein/high-density lipoprotein ratio (P=0.03) compared with placebo
therapy. No statistically significant changes were found in fasting plasma
glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in
the uric acid level were found for SGLT2 inhibitors versus placebo therapy
(P=0.005) or active control (P<0.001). Although no significant change in levels
of ketones occurred (P=0.93), patients receiving SGLT2 inhibitors were at greater
risk of increased ketone bodies. Events suggestive of urinary tract infection and
pollakiuria presented the greatest risk for patients receiving SGLT2 inhibitors
versus active control or placebo therapy. CONCLUSION: SGLT2 inhibitors
significantly decreased HbA1c, body weight, and the low-density lipoprotein/high
density lipoprotein ratio and were found to be safe and well tolerated in type 2
diabetes mellitus patients. Further randomized control trials are required to
establish their risk for ketoacidosis.
PMID- 27486330
TI - Prevalence and perception of smoking habits among the Palestinian population in
the Gaza Strip.
AB - BACKGROUND: The Gaza Strip is a densely populated place with ~2 million
inhabitants in an area of 365 km(2). The aim of this study was to determine the
smoking prevalence in the Gaza Strip and to identify the perception of the
Palestinian population on smoking. METHOD: A cross-sectional study was conducted
in the Gaza Strip, Palestinian territories, during the period from June to
September 2014. Convenient sampling method was adopted. A structured pretested
questionnaire was used. RESULTS: A total of 600 adults aged 15 years or older
completed the questionnaires with a response rate of 83.3%. The prevalence rate
of smoking was 26.3%, with a significantly higher rate among males (31%) than
females (6.9%) (P<0.001). The mean starting age was 17.4+/-3.9 years. The study
revealed that influence of friends is the major reason for initiation of smoking
and the most influential factor in convincing smokers to quit was the family.
Smokers' knowledge about smoking risks motivates them to try stop smoking (64.9%)
or desire to stop smoking (65.2%). CONCLUSION: The study revealed that tobacco
use is significantly prevalent in the Gaza Strip. The author recommends rapid
antismoking campaigns with stress on the family role and massive intervention
programs to encourage young people to change their behavior toward smoking.
PMID- 27486329
TI - Biomarkers and the prediction of atrial fibrillation: state of the art.
AB - Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in
clinical practice, and it places a substantial burden on the health care system.
Despite improvements in our understanding of AF pathophysiology, we have yet to
develop targeted preventive therapies. Recently, numerous biological markers have
been identified to aid in the prediction of future AF events. Subclinical markers
of atrial stress, inflammation, endothelial dysfunction, kidney dysfunction, and
atherosclerosis have been linked to AF. The connection between these markers and
AF is the identification of subclinical states in which AF propagation is likely
to occur, as these conditions are associated with abnormal atrial remodeling and
fibrosis. Additionally, several risk scores have been developed to aid in the
identification of at-risk patients. The practicing clinician should be aware of
these subclinical markers, as several of these markers improve the predictive
abilities of current AF risk scores. Knowledge of these subclinical markers also
provides clinicians with a better understanding of AF risk factors, and the
opportunity to reduce the occurrence of AF by incorporating well-known
cardiovascular disease risk factor modification strategies. In this review, we
highlight several novel biological markers that have improved our understanding
of AF pathophysiology and appraise the utility of these markers to improve our
ability to predict future AF events.
PMID- 27486331
TI - Clinical study on the influence of motion and other factors on stereotactic
radiotherapy in the treatment of adrenal gland tumor.
AB - BACKGROUND: The aim of this study was to investigate the adrenal tumor motion law
and influence factors in the treatment of adrenal gland tumor and provide a
reference value basis for determining the planning target volume margins for
therapy. MATERIALS AND METHODS: The subjects considered in this study were 38
adrenal tumor patients treated with CyberKnife with the placement of 45 gold
fiducials. Fiducials were implanted into each adrenal tumor using beta-ultrasonic
guidance. Motion amplitudes of gold fiducials were measured with a Philips SLS
simulator and motion data in the left-right, anterior-posterior, and cranio
caudal directions were obtained. Multiple linear regression models were used to
analyze influencing factors. t-Test was used for motion amplitude comparison of
different tumor locations along the z-axis. RESULTS: The motion distances were
0.1-0.4 cm (0.27+/-0.07 cm), 0.1-0.5 cm (0.31+/-0.11 cm), and 0.5-1.2 cm (0.87+/
0.21 cm) along the x-, y-, and z-axes, respectively. Motion amplitude along the z
axis may be affected by tumor location, but movement along the other axes was not
affected by age, height, body mass, location, and size. CONCLUSION: The maximum
motion distance was along the z-axis. Therefore, this should be the main
consideration when defining the planning target volume safety margin. Due to the
proximity of the liver, adrenal gland tumor motion amplitude was smaller on the
right than the left. This study analyzed adrenal tumor motion amplitude data to
evaluate how motion and other factors influence the treatment of adrenal tumor
with a goal of providing a reference for stereotactic radiotherapy boundary
determination.
PMID- 27486332
TI - Lung cancer with concurrent EGFR mutation and ROS1 rearrangement: a case report
and review of the literature.
AB - ROS1 rearrangement has recently emerged as a new molecular subtype in non-small
cell lung cancer, and is predominantly found in lung adenocarcinomas compared
with other oncogenes such as EGFR, KRAS, or ALK. Patients who have both mutations
are extremely rare. Here we report a 50-year-old female diagnosed with
adenocarcinoma with sarcomatoid differentiation, who was shown to have EGFR and
ROS1 mutations. The patient was treated surgically and received three cycles of
adjuvant postoperative chemotherapy. In addition, we reviewed the previously
reported cases and related literature. This presentation will provide further
understanding of the underlying molecular biology and optimal treatment for non
small cell lung cancer patients with more than one driver mutation.
PMID- 27486333
TI - MicroRNA-194 promotes the growth, migration, and invasion of ovarian carcinoma
cells by targeting protein tyrosine phosphatase nonreceptor type 12.
AB - Ovarian carcinoma is the most lethal gynecologic malignancy among women. Ovarian
cancer metastasis is the main reason for poor prognosis. MicroRNAs (miRNAs) have
been shown to play an important role in tumorigenesis and metastasis in various
cancers by affecting the expression of their targets. In this study, we explored
the role of miR-194 in ovarian cancer. Real-time polymerase chain reaction assays
showed that miR-194 was significantly upregulated in ovarian cancer tissues.
Overexpression of miR-194 in ovarian cancer cells promotes cell proliferation,
migration, and invasion; in contrast, inhibition of the expression of miR-194 has
the opposite effects. Meanwhile, bioinformatics tools were used to identify
protein tyrosine phosphatase nonreceptor type 12 (PTPN12) as a potential target
of miR-194. The luciferase assay showed that miR-194 directly binds to the 3'
untranslated region of PTPN12. Western blot analysis and quantitative real-time
polymerase chain reaction assay revealed that PTPN12 expression was negatively
associated with miR-194 expression in both ovarian cancer tissues and cells.
Thus, we conclude that miR-194 targets PTPN12 and functions as an oncogene in
ovarian cancer cells. This novel pathway may provide a new insight to explain
ovarian cancer development and metastasis.
PMID- 27486334
TI - Ectopic micronodular thymoma with lymphoid stroma in the cervical region: a rare
case associated with Langerhans cells proliferation.
AB - Micronodular thymoma (MNT) with lymphoid stroma is a rare thymic epithelial
neoplasm with the characteristics of multiple nodules separated by abundant
lymphoid stroma. MNTs mainly arise in the anterior mediastinum and thymus, while
ectopic MNTs are extremely rarely seen. Here, we report an ectopic MNT that
occurred in the neck of a 62-year-old woman. There were also scattered
eosinophilic granulocytes and S100(+)/CD1a(+) Langerhans cells within the tumor.
This case provides a better understanding of such rare, poorly understood cases.
PMID- 27486336
TI - Association between CD14 SNP -159 C/T and gastric cancer: an independent case
control study and an updated meta-analysis.
AB - PURPOSE: The association between CD14 -159C/T polymorphism and the susceptibility
to gastric cancer (GC) has been reported. However, the results were inconclusive.
In the present study, a case-control study and a meta-analysis were performed to
assess the possible association between -159C/T in the CD14 gene and GC risk.
PATIENTS AND METHODS: Relevant studies were searched in several databases
including PubMed, Web of Science, EMBASE, Chinese National Knowledge
Infrastructure database, and Wanfang database (last search was performed on
December 30, 2015). In addition, a case-control study involving 164 GC cases and
169 controls was also performed in the analysis. Statistical analysis was
performed by the software Revman5.3. RESULTS: A total of ten published studies
and the present case-control study involving 2,844 GC and 3,983 controls were
included for the meta-analysis. The analysis result indicated that the T allele
of CD14 -159C/T polymorphism did not confer risk for GC (in our study: [P=0.93];
in the meta-analysis: T vs 2N odds ratio =1.28 and 95% confidence interval (CI)
=0.95-1.24, [P=0.24]). However, we found a significant association in the
recessive model (in our study: TT vs TC+CC [P=0.04]; in the meta-analysis: TT vs
TC+CC odds ratio =1.12 and 95% CI =1.01-1.26, [P=0.04]). Furthermore, a subgroup
analysis by ethnicity showed that TT genotype was significantly associated with
GC in Asian (odds ratio =1.17 and 95% CI =1.02-1.34, [P=0.02]) but not in
Caucasian. CONCLUSION: Our results highlight the TT genotype of CD14 -159C/T as a
genetic susceptibility factor for gastric cancer, particularly, in Asians and
population-based controls.
PMID- 27486337
TI - Evaluation of MMP-9 and MMP-2 and their suppressor TIMP-1 and TIMP-2 in
adenocarcinoma of esophagogastric junction.
AB - OBJECTIVE: Adenocarcinoma of esophagogastric junction (AEG) is a lethal
malignancy featured with early metastasis, poor prognosis, and few treatment
options. Matrix metalloproteinase (MMP) and metalloproteinase suppressor (TIMP)
have been considered to be associated with cancer invasion and metastasis. In our
study, we evaluated expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in AEG and
their correlation with clinicopathological parameters and the overall survival
rate. METHODS: Expressions of MMP-9, MMP-2, TIMP-1, and TIMP-2 in specimens from
120 AEGs were detected by immunohistochemistry. The correlations between
expressions of these four proteins and clinicopathological characters were
analyzed by chi-square test. Moreover, the prognostic value of these four
biomarkers was evaluated by univariate analysis with Kaplan-Meier method and
multivariate analysis with Cox regression model. RESULTS: The positive expression
rate of MMP-9, MMP-2, TIMP-1, and TIMP-2 was 65%, 53%, 70%, and 49%,
respectively, in the detected 120 AEG samples. MMP-9 was significantly associated
with poorly histological differentiation (P=0.001), lymph node metastasis
(P=0.007), and UICC stage (P=0.008). TIMP-1 showed significantly reversed
correlations with histological differentiation (P=0.001), lymph node metastasis
(P=0.007), and Union for International Cancer Control stage (P=0.008). Univariate
analysis revealed that lymph node metastasis (P=0.002), depth of invasion
(P=0.050), and MMP-9+/TIMP-1 phonotype (P<0.001) were significantly associated
with the overall survival rate. Multivariate analyses demonstrated that MMP
9+/TIMP-1-phenotype was an independent prognostic factor in AEGs. CONCLUSION:
Detection of MMP-9 and TIMP-1 expression allows stratification of AEG patients
into different survival categories and can be useful for precise individual
evaluation and survival prediction.
PMID- 27486335
TI - Endocannabinoid system as a regulator of tumor cell malignancy - biological
pathways and clinical significance.
AB - The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs),
endogenous cannabinoids, and enzymes responsible for their synthesis, transport,
and degradation of (endo)cannabinoids. To date, two CBs, CB1 and CB2, have been
characterized; however, orphan G-protein-coupled receptor GPR55 has been
suggested to be the third putative CB. Several different types of cancer present
abnormal expression of CBs, as well as other components of ECS, and this has been
shown to correlate with the clinical outcome. Although most effects of
(endo)cannabinoids are mediated through stimulation of classical CBs, they also
interact with several molecules, either prosurvival or proapoptotic molecules. It
should be noted that the mode of action of exogenous cannabinoids differs
significantly from that of endocannabinoid and results from the studies on their
activity both in vivo and in vitro could not be easily compared. This review
highlights the main signaling pathways involved in the antitumor activity of
cannabinoids and the influence of their activation on cancer cell biology. We
also discuss changes in the expression pattern of the ECS in various cancer types
that have an impact on disease progression and patient survival. A growing amount
of experimental data imply possible exploitation of cannabinoids in cancer
therapy.
PMID- 27486338
TI - Smartphone applications to aid weight loss and management: current perspectives.
AB - The development and dissemination of smart devices has cultivated a global
environment of hyperconnectivity and increased our access to information. The
paralleled launch and success of the Mobile Health industry has created a market
of commercially available applications or "apps" along with tools or sensors,
which allow the user to receive and collect personal health information. Apps and
accompanying tools now allow an individual to "self-digitize" and, pertaining to
weight management, monitor their body weight, caloric intake, physical activity,
and more. These products possess the ability to improve the scalability of
traditional in-person weight management services considering their near ubiquity,
affordability, and capability to deliver information directly and personally to
the user. However, similar to the dietary supplement market, the anecdotal value
of these products has driven their popularity and acceptance by the general
public without requirement of scientific validation or, in the area of weight
management or diet/exercise, validation of the safety and efficacy by the Food
and Drug Administration prior to market launch. By conducting a literature and
clinical trial search, we found remarkably few active, completed, or published
studies testing the efficacy of smart device applications using randomized
controlled trials. Research efforts must be focused on illuminating the efficacy
of behavioral interventions and remote self-monitoring for weight
loss/maintenance treatment with true, randomized controlled trials.
PMID- 27486339
TI - Real-world glycemic outcomes in patients with type 2 diabetes initiating
exenatide once weekly and liraglutide once daily: a retrospective cohort study.
AB - AIM: The glucagon-like peptide-1 receptor agonists exenatide once weekly (QW) and
liraglutide once daily (QD) have demonstrated improvements in glycemic outcomes
in patients with type 2 diabetes mellitus in randomized clinical trials. However,
little is known about their real-world comparative effectiveness. This
retrospective cohort study used the Quintiles Electronic Medical Record database
to evaluate the 6-month change in glycated hemoglobin (A1C) for patients
initiating exenatide QW or liraglutide QD. METHODS: Patients with type 2 diabetes
mellitus prescribed exenatide QW (n=664) or liraglutide QD (n=3,283) between
February 1, 2012 and May 31, 2013 were identified. Baseline A1C measures were
from 75 days before to 15 days after initiating exenatide QW or liraglutide QD,
with follow-up measures documented at 6 months (+/-45 days). Adjusted linear
regression models compared the difference in mean A1C change. A priori defined
sensitivity analysis was performed in the subgroup of patients with baseline A1C
>=7.0% and no prescription for insulin during the 12-month pre-index period.
RESULTS: For exenatide QW and liraglutide QD, respectively, mean (SD) age of the
main study cohort was 58.01 (10.97) and 58.12 (11.05) years, mean (SD) baseline
A1C was 8.4% (1.6) and 8.4% (1.6), and 48.2% and 54.2% of patients were women. In
adjusted models, change in A1C did not differ between exenatide QW and
liraglutide QD during 6 months of follow-up. Results were consistent in the
subgroup analyses. CONCLUSION: In a real-world setting, A1C similarly improves in
patients initiating exenatide QW or liraglutide QD.
PMID- 27486340
TI - Safety of polyethylene glycol 3350 solution in chronic constipation: randomized,
placebo-controlled trial.
AB - PURPOSE: To evaluate the safety and tolerability of aqueous solution concentrate
(ASC) of polyethylene glycol (PEG) 3350 in patients with functional constipation.
PATIENTS AND METHODS: The patients who met Rome III diagnostic criteria for
functional constipation were randomized in this multicenter, randomized, placebo
controlled, single-blind study to receive once daily dose of PEG 3350 (17 g) ASC
or placebo solution for 14 days. The study comprised a screening period (visit
1), endoscopy procedure (visits 2 and 3), and followup telephone calls 30 days
post-treatment. Safety end points included adverse events (AEs), clinical
laboratory evaluations, vital signs, and others. The primary end points were the
proportion of patients with abnormalities of the oral and esophageal mucosa,
detected by visual and endoscopic examination of the oral cavity and esophagus,
respectively, compared with placebo. A secondary objective was to compare the
safety and tolerability of ASC by evaluating AEs or adverse drug reactions.
RESULTS: A total of 65 patients were enrolled in this study, 31 were randomized
to PEG 3350 ASC and 34 were randomized to placebo, of which 62 patients completed
the study. No patients in either group showed abnormalities in inflammation of
the oral mucosa during visit 2 (before treatment) or visit 3 (after treatment).
Fewer abnormalities of the esophageal mucosa were observed in the PEG 3350 ASC
group than in the placebo group on visit 3, with no significant difference in the
proportion of abnormalities between the treatment groups. Overall, 40 treatment
emergent AEs were observed in 48.4% of patients treated with PEG 3350 ASC, and 41
treatment-emergent AEs were observed in 55.9% of patients treated with placebo -
nonsignificant difference of -7.5% (95% CI: -21.3, 6.3) between treatment groups.
No serious AEs or deaths were reported, and no patient discontinued because of an
AE. CONCLUSION: PEG 3350 ASC is safe and well tolerated in patients with
functional constipation (NCT01885104).
PMID- 27486342
TI - A systematic review and meta-analysis of Harmonic technology compared with
conventional techniques in mastectomy and breast-conserving surgery with
lymphadenectomy for breast cancer.
AB - BACKGROUND: Mastectomy and breast-conserving surgery (BCS) are important
treatment options for breast cancer patients. A previous meta-analysis
demonstrated that the risk of certain complications can be reduced with the
Harmonic technology compared with conventional methods in mastectomy. However,
the meta-analysis did not include studies of BCS patients and focused on a subset
of surgical complications. The objective of this study was to compare Harmonic
technology and conventional techniques for a range of clinical outcomes and
complications in both mastectomy and BCS patients, including axillary lymph node
dissection. METHODS: A comprehensive literature search was performed for
randomized controlled trials comparing Harmonic technology and conventional
methods in breast cancer surgery. Outcome measures included blood loss, drainage
volume, total complications, seroma, necrosis, wound infections, ecchymosis,
hematoma, hospital length of stay, and operating time. Risk of bias was analyzed
for all studies. Meta-analysis was performed using random-effects models for mean
differences of continuous variables and a fixed-effects model for risk ratios of
dichotomous variables. RESULTS: Twelve studies met the inclusion criteria. Across
surgery types, compared to conventional techniques, Harmonic technology reduced
total complications by 52% (P=0.002), seroma by 46% (P<0.0001), necrosis by 49%
(P=0.04), postoperative chest wall drainage by 46% (P=0.0005), blood loss by 38%
(P=0.0005), and length of stay by 22% (P=0.007). Although benefits generally
appeared greatest in mastectomy patients with lymph node dissection, Harmonic
technology showed significant reductions in complications in the BCS study
subgroup. CONCLUSION: In this meta-analysis of both mastectomy and BCS
procedures, the use of Harmonic technology reduced the risk of most complications
by about half across breast cancer surgery patients. These benefits may be due to
superior hemostatic capabilities of Harmonic technology and better dissection,
particularly lymph node dissection. Reduction in complications and other resource
outcomes may engender lower downstream health care costs.
PMID- 27486341
TI - Human serum albumin homeostasis: a new look at the roles of synthesis,
catabolism, renal and gastrointestinal excretion, and the clinical value of serum
albumin measurements.
AB - Serum albumin concentration (CP) is a remarkably strong prognostic indicator of
morbidity and mortality in both sick and seemingly healthy subjects.
Surprisingly, the specifics of the pathophysiology underlying the relationship
between CP and ill-health are poorly understood. This review provides a summary
that is not previously available in the literature, concerning how synthesis,
catabolism, and renal and gastrointestinal clearance of albumin interact to bring
about albumin homeostasis, with a focus on the clinical factors that influence
this homeostasis. In normal humans, the albumin turnover time of about 25 days
reflects a liver albumin synthesis rate of about 10.5 g/day balanced by renal
(~6%), gastrointestinal (~10%), and catabolic (~84%) clearances. The acute
development of hypoalbuminemia with sepsis or trauma results from increased
albumin capillary permeability leading to redistribution of albumin from the
vascular to interstitial space. The best understood mechanism of chronic
hypoalbuminemia is the decreased albumin synthesis observed in liver disease.
Decreased albumin production also accounts for hypoalbuminemia observed with a
low-protein and normal caloric diet. However, a calorie- and protein-deficient
diet does not reduce albumin synthesis and is not associated with
hypoalbuminemia, and CP is not a useful marker of malnutrition. In most disease
states other than liver disease, albumin synthesis is normal or increased, and
hypoalbuminemia reflects an enhanced rate of albumin turnover resulting either
from an increased rate of catabolism (a poorly understood phenomenon) or enhanced
loss of albumin into the urine (nephrosis) or intestine (protein-losing
enteropathy). The latter may occur with subtle intestinal pathology and hence may
be more prevalent than commonly appreciated. Clinically, reduced CP appears to be
a result rather than a cause of ill-health, and therapy designed to increase CP
has limited benefit. The ubiquitous occurrence of hypoalbuminemia in disease
states limits the diagnostic utility of the CP measurement.
PMID- 27486343
TI - One-year assessment of physical activity level in adult Qatari females: a
pedometer-based longitudinal study.
AB - BACKGROUND: Physical inactivity is a growing health concern and has been
identified as the fourth leading risk factor for global mortality. The Arab
region includes countries with some of the world's highest physical inactivity
levels, such as Qatar, more specifically the Qatari female population. OBJECTIVE:
The objective of this study is to assess the physical activity levels of Qatari
national female adults during a 1-year pedometer-based program. MATERIALS AND
METHODS: A total of 549 Qatari national females aged between 18 years and 64
years were included. Data extracted from "Step into Health" program web database
in Qatar were used for analyses. Daily habitual physical activity (daily total
step count and aerobic steps) was assessed through the Omron HJ-324U pedometer.
Step counts were classified as follows: <5,000 steps/d, sedentary; 5,000-7,499
steps/d, low active; and >=7,500 steps/d, physically active. Statistical
significance was set at P-value <=0.05. Descriptive statistics were used, and
habitual physical activity was calculated through repeated measures analysis of
variance to determine the difference across the monitored days. RESULTS: Mean age
was 37.4+/-11.7 years, and median body mass index of 28.8 kg/m(2) (interquartile
range 24.8-33.5). Daily steps for the overall population ranged from 3,505
steps/d to 10,010 steps/d, with a median of 6,008 steps/d. A total of 242 (44.1%)
females were sedentary, 178 (32.4%) were low active, and 129 (23.5%) were
physically active. The physically active group showed a median of 927 aerobic
steps/d (interquartile range 0-4,248). CONCLUSION: Based on the results of this
study, Qatari females are not meeting the global recommendations of physical
activity. Future research might need to consider barriers to physical activity as
well as social, cultural, and environmental factors.
PMID- 27486344
TI - Administration of palmitoylethanolamide in combination with topiramate in the
preventive treatment of nummular headache.
AB - Nummular headache has been recently described as a primary disorder characterized
by head pain exclusively felt in a small rounded area typically 2-6 cm in
diameter, not attributed to another disorder. Both size and shape of the painful
area remain constant since the onset of symptoms. A 57-year-old woman presented
with a history of focal episodic pain in a circumscribed area on the right
parietal region. The administration of standard oral doses of
palmitoylethanolamide and topiramate in combination showed an improvement in pain
symptoms and on pain measuring scales.
PMID- 27486345
TI - Computed tomography and magnetic resonance imaging contrast media injectors:
technical feature review - what is really needed?
AB - There has been little technical innovation over the last few years for contrast
media (CM) injectors that are used for diagnostic imaging (computed tomography
[CT], magnetic resonance imaging [MRI], and hybrid imaging systems, such as
positron emission tomography-CT or magnetic resonance-positron emission
tomography) examinations. The medical need of CM for the enhancement of
diagnostic images has been around for a long time, but the application of the CM
into the blood stream comes with potential medical complications for the patient
and requires a lot of operator experience and training. Most power injector
systems that are currently used can do significantly more than what is typically
required; this complexity however, adds error potential and cost. This paper
focuses on the main features that CM injector systems should have and highlights
the technical developments that are useful to have but which add complexity and
cost, increase setup time, and require intensive training for safe use. CM
injection protocols are very different between CT and MRI, with CT requiring many
more variances, has a need for multiphase protocols, and requires a higher timing
accuracy. A CM injector used in the MRI suite, on the other-hand, could only need
a relatively time insensitive injection with a standard injection flow rate and a
volume that is dependent on the patients' weight. This would make easy and
lightweight systems possible, which are able to safely and accurately perform the
injection task, while allowing full MRI compatibility with relatively low cost
investment and consumable costs.
PMID- 27486346
TI - Clinical applications of therapeutic phlebotomy.
AB - Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is
the preferred treatment for blood disorders in which the removal of red blood
cells or serum iron is the most efficient method for managing the symptoms and
complications. Therapeutic phlebotomy is currently indicated for the treatment of
hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease,
and nonalcoholic fatty liver disease with hyperferritinemia. This review
discusses therapeutic phlebotomy and the related disorders and also offers
guidelines for establishing a therapeutic phlebotomy program.
PMID- 27486348
TI - Computational Representations of Myocardial Infarct Scars and Implications for
Arrhythmogenesis.
AB - Image-based computational modeling is becoming an increasingly used clinical tool
to provide insight into the mechanisms of reentrant arrhythmias. In the context
of ischemic heart disease, faithful representation of the electrophysiological
properties of the infarct region within models is essential, due to the scars
known for arrhythmic properties. Here, we review the different computational
representations of the infarcted region, summarizing the experimental
measurements upon which they are based. We then focus on the two most common
representations of the scar core (complete insulator or electrically passive
tissue) and perform simulations of electrical propagation around idealized
infarct geometries. Our simulations highlight significant differences in action
potential duration and focal effective refractory period (ERP) around the scar,
driven by differences in electrotonic loading, depending on the choice of scar
representation. Finally, a novel mechanism for arrhythmia induction, following a
focal ectopic beat, is demonstrated, which relies on localized gradients in ERP
directly caused by the electrotonic sink effects of the neighboring passive scar.
PMID- 27486347
TI - Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.
AB - The transforming properties of oncogenes are derived from gain-of-function
mutations, shifting cell signaling from highly regulated homeostatic to an
uncontrolled oncogenic state, with the contribution of the inactivating mutations
in tumor suppressor genes P53 and RB, leading to tumor resistance to conventional
and target-directed therapy. On the other hand, this scenario fulfills two
requirements for oncolytic virus infection in tumor cells: inactivation of tumor
suppressors and presence of oncoproteins, also the requirements to engage
malignancy. Several of these oncogenes have a negative impact on the main
interferon antiviral defense, the double-stranded RNA-activated protein kinase
(PKR), which helps viruses to spontaneously target tumor cells instead of normal
cells. This review is focused on the negative impact of overexpression of
oncogenes on conventional and targeted therapy and their positive impact on viral
oncolysis due to their ability to inhibit PKR-induced translation blockage,
allowing virion release and cell death.
PMID- 27486349
TI - No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol
Secreting Adenomas Treated with Mifepristone Before Surgery.
AB - BACKGROUND: Glucocorticoid replacement is commonly required to treat secondary
adrenal insufficiency after surgical resection of unilateral cortisol-secreting
adrenocortical adenomas. Here, we describe a patient with unilateral cortisol
secreting adenomas in which the preoperative use of mifepristone therapy was
associated with recovery of the hypothalamic-pituitary-adrenal (HPA) axis,
eliminating the need for postoperative glucocorticoid replacement. CASE
PRESENTATION: A 66-year-old Caucasian man with type 2 diabetes mellitus,
hyperlipidemia, hypertension, and obesity was hospitalized for Fournier's
gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal
computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1,
and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free
cortisol level was elevated (237 ug/24 hours, reference range 0-50 ug/24 hours).
Hormonal evaluation after resolution of the infection showed an abnormal 8 mg
overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 ug/dL),
suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2-63.3
pg/mL), and low-normal dehydroepiandrosterone sulfate (50.5 ug/dL, male reference
range 30.9-295.6 ug/dL). Because of his poor medical condition and uncontrolled
diabetes, his Cushing's syndrome was treated with medical therapy before surgery.
Mifepristone therapy was started and, within five months, his diabetes was
controlled and insulin discontinued. The previously suppressed ACTH increased to
above normal range accompanied by an increase in dehydroepiandrosterone sulfate
levels, indicating recovery of the HPA axis and atrophic contralateral adrenal
gland. The patient received one precautionary intraoperative dose of
hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL)
and cortisol levels (44.8 ug/dL) were significantly elevated, reflecting an
appropriate HPA axis response to the stress of surgery, and two weeks
postoperatively, ACTH was within normal range and a repeat dexamethasone
suppression test was normal. Six months postoperatively, ACTH was within normal
limits and cortisol was approaching normal. The patient has exhibited no
postoperative signs or symptoms of adrenal insufficiency in 12 months.
CONCLUSION: Preoperative mifepristone therapy was associated with apparent
recovery of the HPA axis prior to unilateral adrenalectomy in a patient with
unilateral adrenal adenomas. Postoperatively, the patient experienced no signs or
symptoms of adrenal insufficiency and no glucocorticoid replacement was required.
PMID- 27486352
TI - Benefits of simulation training in medical education.
PMID- 27486351
TI - Developing a competency-based medical education curriculum for the core basic
medical sciences in an African Medical School.
AB - The College of Medicine of the University of Ibadan recently revised its MBBS and
BDS curricula to a competency-based medical education method of instruction. This
paper reports the process of revising the methods of instruction and assessment
in the core basic medical sciences directed at producing medical and dental
graduates with a sound knowledge of the subjects sufficient for medical and
dental practice and for future postgraduate efforts in the field or related
disciplines. The health needs of the community and views of stakeholders in the
Ibadan medical and dental schools were determined, and the "old" curriculum was
reviewed. This process was directed at identifying the strengths and weaknesses
of the old curricula and the newer competences required for modern-day
medical/dental practice. The admission criteria and processes and the learning
methods of the students were also studied. At the end of the review, an
integrated, system-based, community-oriented, person-centered, and competency
driven curriculum was produced and approved for implementation. Four sets of
students have been admitted into the curriculum. There have been challenges to
the implementation process, but these have been overcome by continuous faculty
development and reorientation programs for the nonteaching staff and students.
Two sets of students have crossed over to the clinical school, and the consensus
among the clinical teachers is that their knowledge and application of the basic
medical sciences are satisfactory. The Ibadan medical and dental schools are
implementing their competency-based medical education curricula successfully. The
modifications to the teaching and assessment of the core basic medical science
subjects have resulted in improved learning and performance at the final
examinations.
PMID- 27486350
TI - Elderly Onset Celiac Disease: A Narrative Review.
AB - Celiac sprue is a chronic disease, which usually occurs in children and young
adults. However, it can develop in any age group, and the prevalence is
increasing even in the elderly population. The atypical patterns of clinical
presentation in this age group sometimes can cause a delay in diagnosis. Given
the lower sensitivity and specificity of serological tests in the aged
population, clinical suspect often arises in the presence of complications
(autoimmune disorders, fractures, and finally, malignancy) and must be supported
by endoscopic and imaging tools. In this review, we highlight the incidence and
prevalence of celiac disease in the elderly, the patterns of clinical
presentation, diagnosis, and the most frequent complications, with the aim of
increasing awareness and reducing the diagnostic delay of celiac disease even in
the elderly population.
PMID- 27486353
TI - Dose-dependent effect of N'-Nitrosodiethylamine on hepatic architecture, RBC
rheology and polypeptide repertoire in Wistar rats.
AB - N'-Nitrosodiethylamine (NDEA) is an effective hepatotoxicant, carcinogen and
mutagen. NDEA-induced hepatic necrosis, through metabolic activation by CYP2E1,
is an extensively used experimental model. In the present study, we analysed the
dose- and time-dependent effect of NDEA on hepatic damage, RBC rheology and
proteomic profile in male Wistar rats. The rats, 5-6 weeks old, were divided into
four groups: Group-1 served as control and received normal saline, Group-2
received a single dose of 200 mg/kg body weight NDEA intraperitoneally (i.p.) and
the animals were sacrificed after one week; the rats of Group-3 received a single
dose of 100 mg/kg body weight NDEA and were sacrificed after one week; Group-4
received 100 mg/kg body weight/wk NDEA for two weeks and were then sacrificed.
Various biochemical parameters such as ALT, AST, ALP and bilirubin were
determined. Further, RBC rheology, histopathology (H&E staining) of liver
biopsies and polypeptide profiling (SDS-PAGE) in sera and liver sections were
also carried out both in control and NDEA treated groups. Our results showed a
significant increase in all the biochemical parameters of the liver function test
(p<0.05). In NDEA treated categories dacryocytes (tear drop cells), schistocytes
(fragmented cells), codocytes (target cells), acanthocytes (spur cells) and
ovalocytes (oval cells) were observed. H & E stained liver biopsies treated with
NDEA showed abnormal liver architecture with severe haemorrhage, neutrophilic
infiltration and dysplastic hepatocytes manifested in a dose-dependent manner.
Software analysis of SDS-PAGE of control and NDEA treated rat sera and liver
revealed qualitative and quantitative differences in polypeptide composition.
Based on the presence/absence, polypeptides were classified in three different
categories: (1) house-keeping, present in all the groups investigated; (2) novel,
present in either control or NDEA treated group at any given time; (3)
differential expression, showing quantitative differences. Our study indicates a
dose and time-dependent hepatocellular damage and proteome profile which is
likely due to NDEA-mediated oxidative stress in rats.
PMID- 27486354
TI - Antioxidant modulation of nevirapine induced hepatotoxicity in rats.
AB - HIV/AIDS related mortality has been dramatically reduced by the advent of
antiretroviral therapy (ART). However, ART presents with associated adverse
effects. One of such adverse effects is hepatotoxicity observed with nevirapine
(NVP) containing ART. Since previous studies showed that NVP hepatotoxicity may
be due to oxidative stress via generation of oxidative radicals, this study
sought to evaluate the protective effects of antioxidants in alleviating NVP
induced hepatotoxicity. Rats were divided into 6 groups with 8 animals per group
and received doses of the antioxidants jobelyn (10.7 mg/kg/day), vitamin C (8
mg/kg/day), vitamin E (5 mg/kg/day) and/or NVP (6 mg/kg/day) for 60 days. The
animals were sacrificed on day 61 by cervical dislocation, blood samples were
collected for biochemical and hematological examination. The liver of the
sacrificed animals was weighed and subjected to histopathological examination.
There was a statistically significant (p<0.05) elevation in MDA level observed in
the NVP group as compared with control. The results further showed non
significant decreases in the levels of MDA in the NVP plus antioxidant groups,
except vitamin C, when compared with the NVP alone group. Vitamin E and Vitamin E
plus C treated groups showed significantly (p<0.05) higher levels of SOD, CAT and
GSH. The results also showed statistically significantly (p<0.05) lower levels of
ALT and AST in the antioxidant treated groups There was an observed significantly
(p<0.05) higher level of TP and urea in the antioxidant treated rats. A
significantly (p<0.05) higher white blood cell count was observed in the
antioxidant groups. Histopathological assessment of the liver extracted from the
rats showed no visible pathology across the groups. Observations from this study
suggest a potentially positive modulatory effect of antioxidants and may be
indicative for the inclusion of antioxidants in nevirapine containing ART.
PMID- 27486355
TI - Physiochemical basis of human degenerative disease.
AB - The onset of human degenerative diseases in humans, including type 2 diabetes,
cardiovascular disease, neurological disorders, neurodevelopmental disease and
neurodegenerative disease has been shown to be related to exposures to persistent
organic pollutants, including polychlorinated biphenyls, chlorinated pesticides,
polybrominated diphenyl ethers and others, as well as to polynuclear aromatic
hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The
onset of these diseases has also been related to exposures to transition metal
ions. A physiochemical mechanism for the onset of degenerative environmental
disease dependent upon exposure to a combination of lipophilic aromatic
hydrocarbons and transition metal ions is proposed here. The findings reported
here also, for the first time, explain why aromatic hydrocarbons exhibit greater
toxicity than aliphatic hydrocarbons of equal carbon numbers.
PMID- 27486356
TI - Effects of teicoplanin on cell number of cultured cell lines.
AB - Teicoplanin is a glycopeptide antibiotic with a wide variation in human serum
half-life. It is also a valuable alternative of vancomycin. There is however no
study on its effect on cultured cells. The aim of the present study was to test
the effect of teicoplanin on cultured cell lines CHO, Jurkat E6.1 and MCF-7. The
cultured cells were exposed to teicoplanin at final concentrations of 0-11000
MUg/ml for 24 hours. To determine cell viability, the 3-(4,5-dimethylthiazol-2
yl)-2,5-diphenyltetrazolium bromide (MTT) test was performed. At low
concentrations of teicoplanin the numbers of cultured cells (due to cell
proliferation) were increased in the three cell lines examined. The maximum cell
proliferation rates were observed at concentrations of 1000, 400, and 200 MUg/ml
of teicoplanin for CHO, MCF-7 and Jurkat cell lines, respectively. Cell toxicity
was observed at final concentrations over 2000, 6000, and 400 MUg/ml of
teicoplanin for CHO, MCF-7 and Jurkat cell lines, respectively. A dose-dependent
manner of cell toxicity was observed. Our present findings indicated that
teicoplanin at clinically used concentrations induced cell proliferation. It
should therefore be used cautiously, particularly in children, pregnant women and
patients with cancer.
PMID- 27486357
TI - Protective effect of Cupressus sempervirens extract against indomethacin-induced
gastric ulcer in rats.
AB - Cupressus sempervirens (C. sempervirens) belongs to the family Cupressaceae. It
is widspread in Northern Africa, Greece, Turkey, North America, Cyprus and Syria.
Cupressuflavone is the major ingredient of the plant leave extract. The aim of
the present study was to evaluate the antiulcerogenic activity of the extract of
C. sempervirens leaves in gastric ulcer tissues induced by indomethacin. The
results of the present study revealed that indomethacin significantly decreased
glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT),
reduced glutathione (GSH), glutathione reductase (GR) and superoxide dismutase
(SOD) levels, while it increased significantly lipid peroxidation (MDA), nitric
oxide (NO) and protein carbonyl (PC) levels in gastric tissue. Furthermore,
indomethacin decreased p53 expression, while it increased bcl-2 expression in
gastric tissue. Pretreatment with 5%, 10% & 20% of the LD50 of C. sempervirens
and cupressuflavone of indomethacin-treated rats restored all the above
parameters to approach normal values. C. sempervirens at the highest dose was
more effective than the two lower doses. C. sempervirens proved more potent than
cupressuflavone. In conclusion, C. sempervirens exerted antiulcerogenic activity
and the effect was dose-dependent and related to the cupressuflavone ingredient
of the plant leave extract.
PMID- 27486358
TI - Probit analysis of comparative assays on toxicities of lead chloride and lead
acetate to in vitro cultured human umbilical cord blood lymphocytes.
AB - This work describes that cytotoxicity of lead chloride and lead acetate to in
vitro cultured lymphocytes from human umbilical cord blood, using four monitoring
methods namely, trypan blue staining, acridine orange/ethidium bromide staining,
3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide (MTT) and neutral
red uptake assays; lead genotoxicity to lymphocytes was monitored by comet assay.
The MIC value in each method was invariably 300 mg/L for PbCl2. Lethal
concentration25 (LC25) values were almost in an agreeable range: 691.83 to 831.76
mg/L; LC50 values in each method were almost in the range: 1174.9 to 1348.9 mg/L;
LC100 values were in the range: 3000 to 3300 mg/L, for lead chloride. Similarly,
The MIC value in each method were invariably 150 mg/L; LC25 values were almost in
the range: 295.12 to 371.53 mg/L; LC50 values were in the range: 501.18 to 588.84
mg/L; LC100 value was 1500 mg/L in all assays, for lead acetate. The comet assay
also indicated that the LC100 values were 3300 mg/L lead chloride and 1500 mg/L
lead acetate. Thus, both cytotoxicity and genotoxicity were recorded at 3300 mg/L
lead chloride and 1500 mg/L lead acetate with lymphocytes.
PMID- 27486359
TI - Endothelium and the effect of activated neutrophils on arterial smooth muscle.
AB - The aim of the study was to analyze the involvement of the endothelium in the
effects of neutrophils (PMNL) on phenylephrine-precontracted isolated rings of
the rat thoracic aorta and to compare their effects with those of peroxynitrite
(ONOO(-)) and hypochlorous acid (HOCl). Activated PMNL-induced contraction of the
precontracted aorta was prevented by the blockade of NO-synthase and by
endothelium removal. In the endothelium-free preparations, the effect of PMNL
reappeared in the presence of sodium nitroprusside. The effect of ONOO(-) and
HOCl significantly differed from that of activated PMNL both in the presence and
absence of the endothelium. It is therefore likely that neither ONOO(-) nor HOCl
generated by transformation of superoxide anion radical (O2 (*-)) produced by
PMNL is involved in their action. Reduction of the relaxant effect of nitric
oxide derived from the endothelium by O2 (*-) seems to be the keystone mechanism
in generation of PMNL-induced contraction.
PMID- 27486360
TI - Toxicological studies of aqueous extract of Acacia nilotica root.
AB - Acacia nilotica is a widely used plant in traditional medical practice in
Northern Nigeria and many African countries. The aim of this study was to
determine the toxicological effects of a single dose (acute) and of repeated
doses (sub-acute) administration of aqueous extract of A. nilotica root in
rodents, following our earlier study on antiplasmodial activity. In the acute
toxicity test, three groups of Swiss albino mice were orally administered aqueous
extract of A. nilotica (50, 300 and 2000 mg/kg body weight) and signs of toxicity
were observed daily for 14 days. In the sub-acute toxicity study, four groups of
12 rats (6 male and 6 female) were used. Group 1 received 10 ml/kg b.w distilled
water (control), while groups 2, 3 and 4 received 125, 250 and 500 mg/kg b.w of
the extract, respectively, for 28 consecutive days by oral gavage. Signs of
toxicity/mortality, food and water intake and body weight changes were observed.
Biochemical parameters were analysed in both plasma and liver homogenate. In the
acute and sub-acute toxicity studies, the extract did not cause mortality. A
significant reduction in the activity of lactate dehydrogenase was observed at
250 and 500 mg/kg b.w, while alanine aminotransferase, aspartate aminotransferase
and alkaline phosphatase activities were significantly higher than control values
at 500 mg/kg b.w. The aqueous extract of A. nilotica was found to be safe in
single dose administration in mice but repeated administration of doses higher
than 250 mg/kg b.w of the extract for 28 days in rats may cause hepatotoxicity.
PMID- 27486361
TI - Lead toxicity: a review.
AB - Lead toxicity is an important environmental disease and its effects on the human
body are devastating. There is almost no function in the human body which is not
affected by lead toxicity. Though in countries like US and Canada the use of lead
has been controlled up to a certain extent, it is still used vehemently in the
developing countries. This is primarily because lead bears unique physical and
chemical properties that make it suitable for a large number of applications for
which humans have exploited its benefits from historical times and thus it has
become a common environmental pollutant. Lead is highly persistent in the
environment and because of its continuous use its levels rise in almost every
country, posing serious threats. This article reviews the works listed in the
literature with recent updates regarding the toxicity of lead. Focus is also on
toxic effects of lead on the renal, reproductive and nervous system. Finally the
techniques available for treating lead toxicity are presented with some recent
updates.
PMID- 27486362
TI - Fatal aluminium phosphide poisoning.
AB - Aluminium phosphide (AlP) is a cheap solid fumigant and a highly toxic pesticide
which is commonly used for grain preservation. AlP has currently aroused interest
with a rising number of cases in the past four decades due to increased use for
agricultural and non-agricultural purposes. Its easy availability in the markets
has increased also its misuse for committing suicide. Phosphine inhibits cellular
oxygen utilization and can induce lipid peroxidation. Poisoning with AlP has
often occurred in attempts to commit suicide, and that more often in adults than
in teenagers. This is a case of suicidal consumption of aluminium phosphide by a
32-year-old young medical anesthetist. Toxicological analyses detected aluminium
phosphide. We believe that free access of celphos tablets in grain markets should
be prohibited by law.
PMID- 27486363
TI - Thimerosal exposure and increased risk for diagnosed tic disorder in the United
States: a case-control study.
AB - A hypothesis testing, case-control study evaluated automated medical records for
exposure to organic-Hg from Thimerosal-containing hepatitis B vaccines (TM-HepB)
administered at specific intervals in the first six-months-of-life among cases
diagnosed with a tic disorder (TD) or cerebral degeneration (CD) (an outcome not
biologically plausibly linked to TM exposure) in comparison to controls; both
cases and controls were continuously enrolled from birth (born from 1991-2000)
within the Vaccine Safety Datalink (VSD) database. TD cases were significantly
more likely than controls to have received increased organic-Hg from TM-HepB
administered within the first month-of-life (odds ratio (OR)=1.59, p<0.00001),
first two-months-of-life (OR=1.59, p<0.00001), and first six-months-of-life
(OR=2.97, p<0.00001). Male TD cases were significantly more likely than male
controls to have received increased organic-Hg from TM-HepB administered within
the first month-of-life (OR =1.65, p<0.0001), first two-months-of-life (OR=1.64,
p<0.0001), and first six months-of-life (OR=2.47, p<0.05), where as female TD
were significantly more likely than female controls to have received increased
organic-Hg from TM-HepB administered within the first six-months-of-life
(OR=4.97, p<0.05). By contrast, CD cases were no more likely than controls to
have received increased organic-Hg exposure from TM-HepB administered at any
period studied within the first six-months-of-life. Although routine childhood
vaccination is considered an important public health tool to combat infectious
diseases, the present study associates increasing organic-Hg exposure from TM
HepB and the subsequent risk of a TD diagnosis.
PMID- 27486364
TI - Plasma cadmium and zinc and their interrelationship in adult Nigerians: potential
health implications.
AB - Zinc (an essential trace element) and cadmium (a ubiquitous environmental
pollutant with acclaimed toxicity) have been found to occur together in nature,
with reported antagonism between the two elements. The present study aimed at
determination of plasma levels of zinc (Zn) and cadmium (Cd) and their
interrelationship in adult Nigerians. The series comprised adults (n=443) aged
>=18 yrs (mean +/- SD 38.4+/-13.7 yrs), consisting of 117 males, 184 non-pregnant
and 140 pregnant females. Sociodemographic data were collected by questionnaire
while anthropometrics were determined using standard methods. Plasma Cd and Zn
were determined by using an atomic absorption spectrophotometer. The mean plasma
zinc and cadmium were 94.7+/-18.1 MUg/dl and 0.150+/-0.548 MUg/dl, respectively.
Age, sex, pregnancy, and parity had no effect on either plasma Zn or Cd. Although
educational level had no effect on plasma Zn, it had a significant effect on Cd;
subjects possessing either secondary or tertiary education had significantly
lower plasma Cd than subjects without formal education. Moreover, there seemed to
be an inverse relationship between Cd and Zn, but this was not statistically
significant (r=-0.089; p=0.061). Although plasma Zn was not related to BMI
(r=0.037; p=0.432), Cd was significantly negatively correlated with BMI (r=
0.124; p=0.009). It may be concluded that adult Nigerians in Ebonyi State have
elevated plasma levels of Cd, with apparent impact on the levels of plasma Zn.
This has important public health implications considering the essential roles of
Zn in the protection of Cd mediated adverse health effects. While food
diversification is recommended to improve plasma Zn, efforts should be made to
reduce exposure to Cd to mitigate partially its possible adverse effects.
PMID- 27486365
TI - Altered differential hemocyte count in 3rd instar larvae of Drosophila
melanogaster as a response to chronic exposure of Acephate.
AB - Acephate, an organophosphate (OP) pesticide, was used to investigate the effects
of its chronic exposure on hemocyte abundance in a non-target dipteran insect
Drosophila melanogaster. For this purpose, six graded concentrations ranging from
1 to 6 MUg/ml were selected, which are below the reported residual values (up to
14 MUg/ml) of the chemical. 1(st) instar larvae were fed with these
concentrations up to the 3(rd) instar stage and accordingly hemolymph smears from
these larvae were prepared for differential hemocyte count. Three types of cells
are found in Drosophila hemolymph, namely, plasmatocytes, lamellocytes and
crystal cells. Plasmatocyte count was found to decrease with successive increase
in treatment concentrations. Crystal cells showed an increasing trend in their
number. Though the number of lamellocytes was very low, a bimodal response was
noticed. Lamellocyte number was found to increase with the initial three
concentrations, followed by a dose dependent reduction in their number. As
hemocytes are directly linked to the immune system of fruit flies, fluctuations
in normal titer of these cells may affect insect immunity. Hemocytes share
homologies in their origin and mode of action with the immune cells of higher
organisms including man. Thus the present findings suggest that immune cells of
humans and other organisms may be affected adversely under chronic exposure to
Acephate.
PMID- 27486366
TI - Toxicological evaluation of the aqueous stem bark extract of Bridelia ferruginea
(Euphorbiaceae) in rodents.
AB - Bridelia ferruginea is a woody shrub that grows in the Savannah or rain forests
of Africa and has traditionally been used to treat diabetes, arthritis and boils.
Despite all these uses, extensive toxicological evaluation has not been carried
out. The aim of the present investigation was to evaluate the sub-chronic
toxicological effects of the stem bark aqueous extract of Bridelia ferruginea in
rats. The lethal dose (LD50) was determined using probit analysis and graded
doses of the extract (250-4000 mg/kg) were administered to the animals via oral
and intraperitoneal routes and observed for mortality, behavioral changes and
signs of toxicity. Sub-chronic toxicity study was carried out at doses of 1 000,
2 000 and 4 000 mg/kg administered daily for 60 days. The animals were sacrificed
after 60 days. Blood was collected for biochemical (renal and hepatic),
hematological, oxidative stress, sperm and histopathological examinations, using
standard methods. LD50 of the extract was estimated as >4 000 mg/kg orally;
neither significant visible signs of toxicity nor mortality were observed. There
were no significant differences in the animals and organ weights, hematological
and biochemical parameters in the treated groups compared to the control group.
However, a significant increase (p<0.05) in the level of lipid peroxidation and a
significant (p<0.05) decrease in sperm count were observed in the treated animals
compared with the control group. The stem-bark aqueous extract of Bridelia
ferruginea was found to be relatively safe, though it has the potential to cause
lipid peroxidation and damage sperm quality and should thus be used with caution.
PMID- 27486367
TI - Chemopreventive role of Coriandrum sativum against gentamicin-induced renal
histopathological damage in rats.
AB - Drug induced nephrotoxicity is one of the most common causes of renal failure.
Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential.
Natural antioxidants from plants demonstrate a number of biotherapeutic
activities. Coriander is an important medicinal plant known for its
hepatoprotective, diuretic, carminative, digestive and antihelminthic potential.
This study was designed to investigate whether the extract of Coriandrum sativum
ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander
powder was coarsely grinded and subjected to defatting by petroleum ether and
further with ethyl acetate. The extract was filtered and subjected to
phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was
determined by the OECD Guideline (423). Animals were divided into four groups.
The first group served as positive control, while the second group was toxic
control (gentamicin treated). The third and fourth group were treated with the
extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed
and biochemical and histopathological studies were carried out. Phytochemical
screening of the extract demonstrated Coriandrum sativum to be rich in
flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the
use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum
sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased
creatinine levels in the animals, along with a decrease in serum urea and blood
urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal
histological lesions. It is concluded that Coriandrum sativum is a potential
source of nephroprotective phytochemical activity, with flavonoids and
polyphenols as the major components.
PMID- 27486369
TI - The neurochemical profile of the hippocampus in isoflurane-treated and
unanesthetized rat pups.
AB - In vivo study of cerebral metabolism in neonatal animals by high-resolution
magnetic resonance spectroscopy (MRS) is an important tool for deciphering the
developmental origins of adult diseases. Up to date, all in vivo spectrum
acquisition procedures have been performed in neonatal rodents under anesthesia.
However, it is still unknown if the inhaled anesthetic isoflurane, which is
commonly used in magnetic resonance imaging studies, could affect metabolite
levels in the brain of neonatal rats. Moreover, the unanesthetized MRS
preparation that uses neonatal rodent pups is still lacking. Here, a novel
restraint protocol was developed for neonatal rats in accordance with the
European Directive 2010/63/EU. This protocol shares the same gradation of
severity as the protocol for non-invasive magnetic resonance imaging of animals
with appropriate sedation or anesthesia. Such immobilization of neonatal rats
without anesthesia can be implemented for MRS studies when an interaction between
anesthetic and target drugs is expected. Short-term isoflurane treatment did not
affect the levels of key metabolites in the hippocampi of anesthetized pups and,
in contrast to juvenile and adult rodents, it is suitable for MRS studies in
neonatal rats when the interaction between anesthetic and target drugs is not
expected.
PMID- 27486370
TI - Damascenine induced hepatotoxicity and nephrotoxicity in mice and in vitro
assessed human erythrocyte toxicity.
AB - Nigella damascena seed is characterized by the presence of the major alkaloid,
damascenine and its related metabolites. To our knowledge, no detailed subchronic
toxicological assessment of damascenine (DA) has been reported. The present study
evaluated the potential toxicity of DA in vivo after sub-chronic intraperitoneal
(i.p) administration in mice and in vitro following human erythrocyte hemolysis.
In vivo, a total of 48 adult male and female Swiss albino mice were used in a sub
chronic toxicity study. The mice received intraperitoneally two doses of DA (20
and 100 mg/kg) for 28 days. Food intake, body weight and central body temperature
were measured during the experiment. After completion of drug treatment,
biochemical and histological analyses were performed. No mortality was observed
in any of the treatment groups of mice, showing no toxic effects during the
study. Neither were biochemical parameters altered; no significant differences
were observed concerning glucose, bilirubin, aspartate transaminase (AST),
alanine aminotransferase (ALT), urea, and creatinine parameters. No
histopathological alterations were found in kidney and liver structures. In
vitro, we focused on the human erythrocyte hemolytic process in the presence of
several concentrations of DA. High level concentration of 1 000 MUg/ml of DA
revealed normal cell shapes and absence of hemolysis and deformation.
PMID- 27486368
TI - Protective efficacy of folic acid and vitamin B12 against nicotine-induced
toxicity in pancreatic islets of the rat.
AB - Although cigarette smoking is associated with insulin resistance and an increased
risk for type 2 diabetes, few studies have examined the effect of nicotine on the
adult endocrine pancreas. In this study, male Wister rats were treated with
nicotine (3 mg/kg body weight/ day) with or without supplementation of folic acid
(36 MUg/kg body weight/day) or vitamin B12 (0.63 MUg/kg body weight/day) alone or
in combination. Fasting blood glucose, insulin and HBA1C level and different
oxidative and anti-oxidative stress parameters were measured and pancreatic
tissue sections were stained with eosin-haematoxylene. Data were analysed by
nonparametric statistics. The results revealed that nicotine induced prediabetes
condition with subsequent damage to pancreatic islets in rats. Nicotine also
caused oxidative stress in pancreatic tissue as evidenced by increased nitric
oxide and malondialdehyde level and decreased superoxide dismutase, catalase and
reduced glutathione level. Compared to vitamin B12 supplementation, folic acid
blunted the nicotine-induced toxicity in pancreatic islets with higher efficacy.
Further, folic acid and vitamin B12 in combination were able to confer
significant protection on pancreatic islets against nicotine induced toxicity.
These results suggest that supplementation of folic acid and vitamin B12 in
combination may be a possible strategy of detoxification against nicotine-induced
toxicity in pancreatic islets of the rat.
PMID- 27486371
TI - Antitumor activity and antioxidant status of Streblus asper bark against Dalton's
ascitic lymphoma in mice.
AB - Streblus asper Lour (Moraceae), commonly known as Siamee Rough Brush in English
is widely distributed in subtropical Asia and traditionally used for several
medicinal purposes. In the present study, the ethyl acetate fraction of the
methanol extract from Streblus asper bark (EASA) was evaluated for antitumor
effect against Dalton's ascitic lymphoma (DAL) in Swiss albino mice. Twenty-four
hours after intraperitoneal inoculation of DAL cells in mice, EASA was
administered intraperitoneally at 200 and 400 mg/kg body weight for 9 consecutive
days. On the 10th day, half of the mice were sacrificed to determine the tumor
growth parameters, and the rest were kept alive for survival assessment.
Hematological, serum biochemical and tissue (liver, kidney) antioxidant profiles
were also determined. EASA exhibited significant and dose dependent decrease in
tumor growth parameters and increased survival of DAL bearing animals. EASA
significantly and dose-dependently normalized the altered hematological, serum
biochemical and tissue antioxidant parameters as compared with the DAL control
mice. From the present study it may be concluded that S. asper bark possesses
remarkable antitumor efficacy mediated by amelioration of oxidative stress by
multiple mechanisms.
PMID- 27486372
TI - Zinc asparaginate supplementation induces redistribution of toxic trace elements
in rat tissues and organs.
AB - The primary objective of the current study was the investigation of the influence
of zinc asparaginate supplementation for 7 and 14 days on toxic metal and
metalloid content in rat organs and tissues. Rats obtained zinc asparaginate in
doses of 5 and 15 mg/kg/day for 7 and 14 days. At the end of the experiment rat
tissues and organs (liver, kidney, heart, m. gastrocnemius, serum, and hair) were
collected for subsequent analysis. Estimation of Zn, Al, As, Li, Ni, Sn, Sr
content in the harvested organs was performed using inductively coupled plasma
mass spectrometry at NexION 300D. The obtained data showed that intragastric
administration of zinc significantly increased liver, kidney and serum zinc
concentrations. Seven-day zinc treatment significantly affected the toxic trace
element content in the animals' organs. Zinc supplementation significantly
decreased particularly liver aluminium, nickel, and tin content, whereas lead
tended to increase. Zinc-induced changes in kidney metal content were
characterized by elevated lithium and decreased nickel concentration. Zinc
induced alteration of myocardical toxic element content was multidirectional.
Muscle aluminium and lead concentration were reduced in response to zinc
supplementation. At the same time, serum and hair toxic element concentrations
remained relatively stable after 7-day zinc treatment. Zinc asparaginate
treatment of 14 days significantly depressed liver and elevated kidney lithium
content, whereas a significant zinc-associated decrease was detected in kidney
strontium content. Zinc supplementation for 14 days resulted also in
multidirectional changes in the content of heart toxic elements. At the same
time, significant zinc-associated decrease in muscle lithium and nickel levels
was observed. Fourteen-day zinc treatment resulted in significantly increased
serum arsenic and tin concentrations, whereas hair trace element content remained
relatively stable. Generally, the obtained data indicate a significant
redistribution of toxic metals in the animal organism under zinc supplementation.
PMID- 27486373
TI - Local salt substitutes "Obu-otoyo" activate acetylcholinesterase and
butyrylcholinesterase and induce lipid peroxidation in rat brain.
AB - Evidence has shown that ingestion of heavy metals can lead to neurodegenerative
diseases. This study aimed to investigate the neurotoxic potential of salt
substitutes (Obu-Otoyo); salt A (made by burning palm kernel shaft then soaked in
water overnight and the extract from the resulting residue is used as the salt
substitute) and salt B (an unrefined salt mined from a local site at Ilobu town,
Osun-State, Nigeria) by assessing their effect on some key enzymes linked with
neurodegenerative disease [acetylcholinesterase (AChE) and butyrylcholinesterase
(BChE) activities] as well as on malondialdehyde (MDA) content of the rat brain.
Salt substitutes were fed to normal rats as dietary inclusion at doses of 0.5 and
1.0% for 30 days. Thereafter, the effect of the salt substitutes on AChE and BChE
activities as well as on MDA level in the rat brain was determined. The results
revealed that the salt substitutes caused a significant (p<0.05) increase in both
AChE and BChE activity and also induced lipid peroxidation in the brain of rats
in vivo as well as under in vitro condition in a dose-dependent manner. The
effect of the salt substitutes on AChE and BChE activities could be attributed to
the presence of some toxic heavy metals. Therefore, the ability of the salt
substitutes to induce lipid peroxidation and activate AChE and BChE activities
could provide some possible mechanism for their neurotoxic effect.
PMID- 27486374
TI - Blood level of cadmium and lead in occupationally exposed persons in Gwagwalada,
Abuja, Nigeria.
AB - This study was designed to assess the blood levels of cadmium and lead in some
occupationally exposed individuals and compare the values with non-exposed
individuals, with the aim of increasing the awareness of health risk caused by
these heavy metals. A total of 120 subjects (64 occupationally exposed and 56 non
exposed subjects) with the age range of 15-40 years were studied in cross
sectional study conducted between September 2012 and February 2013 in Gwagwalada
area of Abuja, Nigeria. Blood cadmium and lead were analyzed using an atomic
absorption spectrophotometer (AAS). The respective mean blood levels of cadmium
and lead were 11.63+/-1.73 MUg/dl and 45.43+/-6.93 MUg/dl in occupationally
exposed subjects, while in non-exposed subjects 2.03+/-0.55 MUg/dl and 12.08+/
2.87 MUg/dl. The results show that occupational exposure increases the blood
level of cadmium and lead, which consequently increases the health risk of the
exposed individuals.
PMID- 27486375
TI - Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative
stress indices in male rats.
AB - Cadmium (Cd) is an environmental toxic metal implicated in lipid abnormalities.
The present study was designed to elucidate the possible association between
chronic exposure to Cd concentration and alterations in plasma lipid,
lipoprotein, and oxidative stress indices in rats. Sixteen male rats were
assigned to 2 groups of 8 rats each (test and control). The Cd-exposed group
obtained drinking water containing cadmium chloride (CdCl2) in the concentration
of 2.0 mg Cd/L in drinking water for 3 months. At the end of the experimental
period, blood samples were obtained to determine the changes of serum
triglycerides (TG), total cholesterol (TC), highdensity lipoprotein cholesterol
(HDL-C), low-density lipoprotein cholesterol (LDL-C), reduced glutathione (GSH),
malondialdehyde (MDA) and also serum Cd contents. The results of the present
study indicated that Cd administration significantly increased the serum levels
of TG, TC, LDL-C, MDA and Cd with reduction in the HDL-C and GSH levels. In
conclusion, evidence is presented that chronic exposure to low Cd concentration
can adversely affect the lipid and lipoprotein profile via lipid peroxidation.
PMID- 27486376
TI - Expression of calmodulin-related genes in lead-exposed mice.
AB - The toxic metal lead is a widespread environmental polutant that can adversely
affect human health. However, the underlying mechanisms of lead-induced toxicity
are still largely unknown. The mechanism of lead toxicity was presumed to involve
cross reaction between Pb(2+) and Ca(2+) with calmodulin dependent systems. The
aim of the present study was thus to identify differential expression of
calmodulin-related genes in the spleen of lead-exposed mice. We performed
microarray analysis to identify differentially expressed genes. RNAs from spleen
tissue of lead exposed animals (n=6) and controls (n=6) were converted to labeled
cRNA and hybridized to Illumina mouse WG-6_v2_Bead Chip. Expression profiles were
analyzed using Illumina BeadStudio Application. Real-time RT-PCR was conducted to
validate the microarray data. By microarray analysis 5 calmodulin-related genes
(MAP2K6, CAMKK2, CXCR4, PHKA2, MYLK) were found to be differently expressed in
lead exposed compared with control mice (p<0.05). The results of Real-time RT-PCR
showed that MAP2K6 and CAMKK2 were up-regulated and CXCR4 was down-regulated in
lead exposure, but there were no significant differences in PHKA2 and MYLK
expression between the lead exposed and control group. These results show that
lead exposure produced significant changes in expression of a variety of genes in
the spleen and can affect calmodulin-related gene expression.
PMID- 27486377
TI - Long-term changes in brain cholinergic system and behavior in rats following
gestational exposure to lead: protective effect of calcium supplement.
AB - Our earlier studies showed that lactational exposure to lead (Pb) caused
irreversible neurochemical alterations in rats. The present study was carried out
to examine whether gestational exposure to Pb can cause long-term changes in the
brain cholinergic system and behavior of rats. The protective effect of calcium
(Ca) supplementation against Pb toxicity was also examined. Pregnant rats were
exposed to 0.2% Pb (Pb acetate in drinking water) from gestational day (GD) 6 to
GD 21. The results showed decrease in body weight gain (GD 6-21) of dams, whereas
no changes were observed in offspring body weight at different postnatal days
following Pb exposure. Male offspring treated with Pb showed marginal alterations
in developmental landmarks such as unfolding of pinnae, lower and upper incisor
eruption, fur development, eye slit formation and eye opening on postnatal day
(PND) 1, whereas significant alterations were found in the righting reflex (PNDs
4-7), slant board behavior (PNDs 8-10) and forelimb hang performance (PNDs 12
16). Biochemical analysis showed decrease in synaptosomal acetylcholinesterase
(AChE) activity and an increase in acetylcholine (ACh) levels in the cortex,
cerebellum and hippocampus on PND 14, PND 21, PND 28 and in the four-month age
group of rats following Pb exposure. Significant deficits were also observed in
total locomotor activity, exploratory behavior and open field behavior in
selected age groups of Pb-exposed rats. These alterations were found to be
maximal on PND 28, corresponding with the greater blood lead levels observed on
PND 28. Addition of 0.02% Ca to Pb reversed the Pb-induced impairments in the
cholinergic system as well as in behavioral parameters of rats. In conclusion,
these data suggest that gestational exposure to Pb is able to induce long-term
changes in neurological functions of offspring. Maternal Ca administration
reversed these neurological effects of Pb later in life, suggesting a protective
effect of calcium in Pb-exposed animals.
PMID- 27486378
TI - Evaluation of miR-9 and miR-143 expression in urine specimens of sulfur mustard
exposed patients.
AB - Sulfur mustard (SM) or mustard gas is a chemical alkylating agent that causes
blisters in the skin (blister gas), burns the eyes and causes lung injury. Some
major cellular pathways are involved in the damage caused by mustard gas such as
NF-kappab signaling, TGF-beta signaling, WNT pathway, inflammation, DNA repair
and apoptosis. MicroRNAs are non-coding small RNAs (19-25 nucleotides) that are
involved in the regulation of gene expression and are found in two forms,
extracellular and intracellular. Changes in the levels of extracellular microRNAs
are directly associated with many diseases, it is thus common to study the level
of extracellular microRNAs as a biomarker to determine the pathophysiologic
status. In this study, 32 mustard gas injured patients and 32healthy subjects
participated. Comparative evaluation of miR-9 and miR-143 expression in urine
samples was performed by Real Time PCR and Graph Pad software. The Mann Whitney t
test analysis of data showed that the expression level of miR-143 and miR-9 had a
significant decrease in sulfur mustard individuals with the respective p-value of
0.0480 and 0.0272 compared to normal samples, with an imbalance of several above
mentioned pathways. It seems that reducing the expression level of these genes
has a very important role in the pathogenicity of mustard gas injured patients.
PMID- 27486379
TI - Modulatory effect of Mangifera indica against carbon tetrachloride induced kidney
damage in rats.
AB - There is little scientific evidence on the local use of Mangifera indica in
kidney diseases. This study investigated the reno-modulatory roles of the aqueous
stem bark extract of Mangifera indica (MIASE) against CCl4-induced renal damage.
Rats were treated intragastrically with 125, 250 and 500 mg/kg/day MIASE for 7
days before and after the administration of CCl4 (3 ml/kg of 30% CCl4, i.p.).
Serum levels of electrolytes (Na+, K+, Cl(-), HCO3(-)), urea and creatinine were
determined. Renal tissue reduced glutathione (GSH), malondialdehyde (MDA),
catalase (CAT), superoxide (SOD) activities were also assessed. The
histopathological changes in kidneys were determined using standard methods. In
CCl4 treated rats the results showed significant (p<0.05) increases in serum Na+,
K+, Cl(-), urea and creatinine. CCl4 also caused significant (p<0.05) decreases
in renal tissue SOD, CAT and GSH and significant (p<0.05) increases in MDA. The
oral MIASE treatment (125-500 mg/kg) was found to significantly (p<0.05)
attenuate the increase in serum electrolytes, urea and creatinine. Similarly,
MIASE significantly (p<0.05) attenuated the decrease in SOD, CAT and GSH levels
and correspondingly attenuated increases in MDA. Mangifera indica may present a
great prospect for drug development in the management of kidney disease with
lipid peroxidation as its etiology.
PMID- 27486380
TI - Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of
Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal
bioassays.
AB - Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn
Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in
the management of diseases, including cancer, in Nigeria. Despite the therapeutic
potentials attributed to these plants, reports on their genotoxicity are scanty.
In this study, the genotoxicity of the aqueous and hydro-methanol extract of
these plants was evaluated using mouse bone marrow micronucleus and sperm
morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus
test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was
first used to assess acute toxicity of the aqueous and hydro-methanol extracts in
Swiss albino mice. For each extract, there were five groups of mice (n=4/group)
treated with different concentrations of the extract as against the negative and
positive control group for the genotoxicity study. In the antigenotoxicity study,
five groups of mice were exposed to five different concentrations of the extracts
along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce
genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in
the genotoxicity and antigenotoxicity groups. Administration of each of the
extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in
mice. At the concentrations tested, all the extracts, except aqueous S. mombin,
increased micronucleated polychromatic erythrocytes. The aqueous and hydro
methanol extracts of N. lotus increased the frequency of aberrant sperm cells.
All the extracts were also able to ameliorate MMS induced genotoxicity in bone
marrow cells of the exposed mice. The results showed the potential of the
extracts to induce somatic and germ cell mutation in male mice. The extracts also
ameliorated the genotoxic effect of MMS.
PMID- 27486381
TI - Toxicological assessment of polyhexamethylene biguanide for water treatment.
AB - Polyhexamethylene biguanide (PHMB) is an antiseptic with antiviral and
antibacterial properties used in a variety of products including wound care
dressings, contact lens cleaning solutions, perioperative cleansing products, and
swimming pool cleaners. There are regulatory concerns with regard to its safety
in humans for water treatment. We decided to assess the safety of this chemical
in Sprague-Dawley rats. PHMB was administered in a single dose by gavage via a
stomach tube as per the manufacturer's instruction within a dose range of 2 mg/kg
to 40 mg/kg. Subchronic toxicity studies were also conducted at doses of 2 mg/kg,
8 mg/kg and 32 mg/kg body weight and hematological, biochemical and
histopathological findings of the major organs were assessed. Administration of a
dose of 25.6 mg/kg, i.e. 1.6 mL of 0.4% PHMB solution (equivalent to 6.4x10(3)
mg/L of 0.1% solution) resulted in 50% mortality. Histopathological analysis in
the acute toxicity studies showed that no histopathological lesions were observed
in the heart and kidney samples but 30% of the animals had mild hydropic changes
in zone 1 of their liver samples, while at a dosage of 32 mg/kg in the subchronic
toxicity studies, 50% of the animals showed either mild hepatocyte cytolysis with
or without lymphocyte infiltration and feathery degeneration. Lymphocyte
infiltration was, for the first time, observed in one heart sample, whereas one
kidney sample showed mild tubular damage. The acute studies showed that the
median lethal dose (LD50) is 25.6 mg/kg (LC50 of 1.6 mL of 0.4% PHMB. Subchronic
toxicological studies also revealed few deleterious effects on the internal
organs examined, as seen from the results of the biochemical parameters
evaluated. These results have implications for the use of PHMB to make water
potable.
PMID- 27486382
TI - Resistance to receptor tyrosine kinase inhibitors in solid tumors: can we improve
the cancer fighting strategy by blocking autophagy?
AB - A growing field of evidence suggests the involvement of oncogenic receptor
tyrosine kinases (RTKs) in the transformation of malignant cells. Constitutive
and abnormal activation of RTKs may occur in tumors either through
hyperactivation of mutated RTKs or via functional upregulation by RTK-coding gene
amplification. In several types of cancer prognosis and therapeutic responses
were found to be associated with deregulated activation of one or more RTKs.
Therefore, targeting various RTKs remains a significant challenge in the
treatment of patients with diverse malignancies. However, a frequent issue with
the use of RTK inhibitors is drug resistance. Autophagy activation during
treatment with RTK inhibitors has been commonly observed as an obstacle to more
efficacious therapy and has been associated with the limited efficacy of RTK
inhibitors. In the present review, we discuss autophagy activation after the
administration of RTK inhibitors and summarize the achievements of combination
RTK/autophagy inhibitor therapy in overcoming the reported resistance to RTK
inhibitors in a growing number of cancers.
PMID- 27486383
TI - miRNA-135a promotes hepatocellular carcinoma cell migration and invasion by
targeting forkhead box O1.
AB - AIMS: Hepatocellular carcinoma (HCC) is the third leading cause of cancer
mortality worldwide. Many microRNAs (miRNAs), small non-coding RNAs, are involved
in regulating cancer cell proliferation, metastasis, migration, invasion and
apoptosis. MAIN METHODS: We investigated the expression of miR-135a in HCC cell
lines and clinical tissues. The effect of miR-135a on migration and invasion of
HepG2 and MHCC-97L were examined using wound healing and Transwell assay. We
determined the expression of miR-135a, forkhead box O1 (FOXO1), matrix
metalloproteinase-2 (MMP-2) and Snail using real-time PCR and western blotting.
KEY FINDINGS: We found miR-135a was upregulated in HCC cell lines and tissues.
miR-135a overexpression promoted HCC cells migration and invasion, whereas miR
135a inhibition suppressed HCC cells migration and invasion. miR-135a
overexpression could upregulate the expression of MMP2, Snail and the
phosphorylation of AKT, but decreased FOXO3a phosporylation. Tumor suppressor
FOXO1 was the direct target for miR-135a. SIGNIFICANCE: Our results suggested
that miR-135a might play an important role in promoting migration and invasion in
HCC and presents a novel mechanism of miRNA-mediated direct suppression of FOXO1
in HCC cells.
PMID- 27486384
TI - Apolipoprotein A-I gene transfer exerts immunomodulatory effects and reduces
vascular inflammation and fibrosis in ob/ob mice.
AB - BACKGROUND: Obesity is associated with vascular inflammation, fibrosis and
reduced high-density lipoproteins (HDL)-cholesterol. We aimed to investigate
whether adenoviral gene transfer with human apolipoprotein (apo) A-I (Ad.A-I),
the main apo of HDL, could exert immunomodulatory effects and counteract vascular
inflammation and fibrosis in ob/ob mice. METHODS: Ad.A-I transfer was performed
in 8 weeks (w) old ob/ob mice, which were sacrificed 7 w later. The aorta was
excised for mRNA analysis and the spleen for splenocyte isolation for subsequent
flow cytometry and co-culture with murine fibroblasts. HDL was added to
mononuclear cells (MNC) and fibroblasts to assess their impact on adhesion
capacity and collagen deposition, respectively. RESULTS: Ad.A-I led to a 1.8-fold
(p < 0.05) increase in HDL-cholesterol versus control ob/ob mice at the day of
sacrifice, which was paralleled by a decrease in aortic TNF-alpha and VCAM-1 mRNA
expression. Pre-culture of MNC with HDL decreased their adhesion to TNF-alpha
activated HAEC. Ad.A-I exerted immunomodulatory effects as evidenced by a
downregulation of aortic NOD2 and NLRP3 mRNA expression and by a 12 %, 6.9 %, and
15 % decrease of the induced proliferation/activity of total splenic MNC, CD4+,
and CD8+ cells in ob/ob Ad.A-I versus control ob/ob mice, respectively (p <
0.05). Ad.A-I further reduced aortic collagen I and III mRNA expression by 62 %
and 66 %, respectively (p < 0.0005), and abrogated the potential of ob/ob
splenocytes to induce the collagen content in murine fibroblasts upon co-culture.
Finally, HDL decreased the TGF-beta1-induced collagen deposition of murine
fibroblasts in vitro. CONCLUSIONS: Apo A-I transfer counteracts vascular
inflammation and fibrosis in ob/ob mice.
PMID- 27486385
TI - Comparative approaches for assessing access to alcohol outlets: exploring the
utility of a gravity potential approach.
AB - BACKGROUND: A growing body of research recommends controlling alcohol
availability to reduce harm. Various common approaches, however, provide
dramatically different pictures of the physical availability of alcohol. This
limits our understanding of the distribution of alcohol access, the causes and
consequences of this distribution, and how best to reduce harm. The aim of this
study is to introduce both a gravity potential measure of access to alcohol
outlets, comparing its strengths and weaknesses to other popular approaches, and
an empirically-derived taxonomy of neighborhoods based on the type of alcohol
access they exhibit. METHODS: We obtained geospatial data on Seattle, including
the location of 2402 alcohol outlets, United States Census Bureau estimates on
567 block groups, and a comprehensive street network. We used exploratory spatial
data analysis and employed a measure of inter-rater agreement to capture
differences in our taxonomy of alcohol availability measures. RESULTS:
Significant statistical and spatial variability exists between measures of
alcohol access, and these differences have meaningful practical implications. In
particular, standard measures of outlet density (e.g., spatial, per capita,
roadway miles) can lead to biased estimates of physical availability that over
emphasize the influence of the control variables. Employing a gravity potential
approach provides a more balanced, geographically-sensitive measure of access to
alcohol outlets. CONCLUSIONS: Accurately measuring the physical availability of
alcohol is critical for understanding the causes and consequences of its
distribution and for developing effective evidence-based policy to manage the
alcohol outlet licensing process. A gravity potential model provides a superior
measure of alcohol access, and the alcohol access-based taxonomy a helpful
evidence-based heuristic for scholars and local policymakers.
PMID- 27486386
TI - Manual-Protocol Inspired Technique for Improving Automated MR Image Segmentation
during Label Fusion.
AB - Recent advances in multi-atlas based algorithms address many of the previous
limitations in model-based and probabilistic segmentation methods. However, at
the label fusion stage, a majority of algorithms focus primarily on optimizing
weight-maps associated with the atlas library based on a theoretical objective
function that approximates the segmentation error. In contrast, we propose a
novel method-Autocorrecting Walks over Localized Markov Random Fields (AWoL-MRF)
that aims at mimicking the sequential process of manual segmentation, which is
the gold-standard for virtually all the segmentation methods. AWoL-MRF begins
with a set of candidate labels generated by a multi-atlas segmentation pipeline
as an initial label distribution and refines low confidence regions based on a
localized Markov random field (L-MRF) model using a novel sequential inference
process (walks). We show that AWoL-MRF produces state-of-the-art results with
superior accuracy and robustness with a small atlas library compared to existing
methods. We validate the proposed approach by performing hippocampal
segmentations on three independent datasets: (1) Alzheimer's Disease Neuroimaging
Database (ADNI); (2) First Episode Psychosis patient cohort; and (3) A cohort of
preterm neonates scanned early in life and at term-equivalent age. We assess the
improvement in the performance qualitatively as well as quantitatively by
comparing AWoL-MRF with majority vote, STAPLE, and Joint Label Fusion methods.
AWoL-MRF reaches a maximum accuracy of 0.881 (dataset 1), 0.897 (dataset 2), and
0.807 (dataset 3) based on Dice similarity coefficient metric, offering
significant performance improvements with a smaller atlas library (< 10) over
compared methods. We also evaluate the diagnostic utility of AWoL-MRF by
analyzing the volume differences per disease category in the ADNI1: Complete
Screening dataset. We have made the source code for AWoL-MRF public at:
https://github.com/CobraLab/AWoL-MRF.
PMID- 27486387
TI - Mitochondrial Dynamics Decrease Prior to Axon Degeneration Induced by Vincristine
and are Partially Rescued by Overexpressed cytNmnat1.
AB - Axon degeneration is a prominent feature of various neurodegenerative diseases,
such as Parkinson's and Alzheimer's, and is often characterized by aberrant
mitochondrial dynamics. Mitochondrial fission, fusion, and motility have been
shown to be particularly important in progressive neurodegeneration. Thus we
investigated these imperative dynamics, as well as mitochondrial fragmentation in
vincristine induced axon degradation in cultured dorsal root ganglia (DRG)
neurons. CytNmnat1 inhibits axon degeneration in various paradigms including
vincristine toxicity. The mechanism of its protection is not yet fully
understood; therefore, we also investigated the effect of cytNmnat1 on
mitochondrial dynamics in vincristine treated neurons. We observed that
vincristine treatment decreases the rate of mitochondrial fission, fusion and
motility and induces mitochondrial fragmentation. These mitochondrial events
precede visible axon degeneration. Overexpression of cytNmnat1 inhibits axon
degeneration and preserves the normal mitochondrial dynamics and motility in
vincristine treated neurons. We suggest the alterations in mitochondrial
structure and dynamics are early events which lead to axon degeneration and
cytNmnat1 blocks axon degeneration by halting the vincristine induced changes to
mitochondrial structure and dynamics.
PMID- 27486388
TI - A Pair of Pharyngeal Gustatory Receptor Neurons Regulates Caffeine-Dependent
Ingestion in Drosophila Larvae.
AB - The sense of taste is an essential chemosensory modality that enables animals to
identify appropriate food sources and control feeding behavior. In particular,
the recognition of bitter taste prevents animals from feeding on harmful
substances. Feeding is a complex behavior comprised of multiple steps, and food
quality is continuously assessed. We here examined the role of pharyngeal
gustatory organs in ingestion behavior. As a first step, we constructed a
gustatory receptor-to-neuron map of the larval pharyngeal sense organs, and
examined corresponding gustatory receptor neuron (GRN) projections in the larval
brain. Out of 22 candidate bitter compounds, we found 14 bitter compounds that
elicit inhibition of ingestion in a dose-dependent manner. We provide evidence
that certain pharyngeal GRNs are necessary and sufficient for the ingestion
response of larvae to caffeine. Additionally, we show that a specific pair of
pharyngeal GRNs, DP1, responds to caffeine by calcium imaging. In this study we
show that a specific pair of GRNs in the pharyngeal sense organs coordinates
caffeine sensing with regulation of behavioral responses such as ingestion. Our
results indicate that in Drosophila larvae, the pharyngeal GRNs have a major role
in sensing food palatability to regulate ingestion behavior. The pharyngeal sense
organs are prime candidates to influence ingestion due to their position in the
pharynx, and they may act as first level sensors of ingested food.
PMID- 27486390
TI - Whisking Kinematics Enables Object Localization in Head-Centered Coordinates
Based on Tactile Information from a Single Vibrissa.
AB - During active tactile exploration with their whiskers (vibrissae), rodents can
rapidly orient to an object even though there are very few proprioceptors in the
whisker muscles. Thus a long-standing question in the study of the vibrissal
system is how the rat can localize an object in head-centered coordinates without
muscle-based proprioception. We used a three-dimensional model of whisker bending
to simulate whisking motions against a peg to investigate the possibility that
the 3D mechanics of contact from a single whisker are sufficient for localization
in head-centered coordinates. Results show that for nearly all whiskers in the
array, purely tactile signals at the whisker base - as would be measured by
mechanoreceptors, in whisker-centered coordinates - could be used to determine
the location of a vertical peg in head-centered coordinates. Both the "roll" and
the "elevation" components of whisking kinematics contribute to the uniqueness
and resolution of the localization. These results offer an explanation for a
behavioral study showing that rats can more accurately determine the horizontal
angle of an object if one column, rather than one row, of whiskers is spared.
PMID- 27486391
TI - Intermittent Theta Burst Over M1 May Increase Peak Power of a Wingate Anaerobic
Test and Prevent the Reduction of Voluntary Activation Measured with Transcranial
Magnetic Stimulation.
AB - Despite the potential of repetitive transcranial magnetic stimulation (rTMS) to
improve performances in patients suffering from motor neuronal afflictions, its
effect on motor performance enhancement in healthy subjects during a specific
sport task is still unknown. We hypothesized that after an intermittent theta
burst (iTBS) treatment, performance during the Wingate Anaerobic Test (WAnT) will
increase and supraspinal fatigue following the exercise will be lower in
comparison to a control treatment. Ten subjects participated in two randomized
experiments consisting of a WAnT 5 min after either an iTBS or a control
treatment. We determined voluntary activation (VA) of the right knee extensors
with TMS (VATMS) and with peripheral nerve stimulation (VAPNS) of the femoral
nerve, before and after the WAnT. T-tests were applied to the WAnT results and a
two way within subject ANOVA was applied to VA results. The iTBS treatment
increased the peak power and the maximum pedalling cadence and suppressed the
reduction of VATMS following the WAnT compared to the control treatment. No
behavioral changes related to fatigue (mean power and fatigue index) were
observed. These results indicate for the first time that iTBS could be used as a
potential intervention to improve anaerobic performance in a sport specific task.
PMID- 27486389
TI - Horizontal Cells, the Odd Ones Out in the Retina, Give Insights into Development
and Disease.
AB - Thorough investigation of a neuronal population can help reveal key aspects
regarding the nervous system and its development. The retinal horizontal cells
have several extraordinary features making them particularly interesting for
addressing questions regarding fate assignment and subtype specification. In this
review we discuss and summarize data concerning the formation and diversity of
horizontal cells, how morphology is correlated to molecular markers, and how fate
assignment separates the horizontal lineage from the lineages of other retinal
cell types. We discuss the novel and unique features of the final cell cycle of
horizontal cell progenitors and how they may relate to retinoblastoma
carcinogenesis.
PMID- 27486392
TI - Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive
Symptoms and Suicidal Ideation.
AB - Although the neuropeptide oxytocin has been associated with enhanced prosocial
behaviors, it has also been linked to aggression and mental health disorders.
Thus, it was suggested that oxytocin might act by increasing the salience of
social stimuli, irrespective of whether these are positive or negative, thus
increasing vulnerability to negative mental health outcomes. The current study (N
= 243), conducted among white university students, examined the relation of
trauma, depressive symptoms including suicidal ideation in relation to a single
nucleotide polymorphism (SNP) within the oxytocin receptor gene (OXTR), rs53576,
and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals
with the polymorphism on both alleles (AA genotype) of the CD38 SNP had
previously been linked to elevated plasma oxytocin levels. Consistent with the
social sensitivity perspective, however, in the current study, individuals
carrying the AA genotype displayed elevated feelings of alienation from parents
and peers as well as increased levels of suicidal ideation. Moreover, they tended
to report elevated depressive symptoms compared to CC homozygotes. It was also
observed that the CD38 genotype moderated the relation between trauma and
suicidal ideation scores, such that high levels of trauma were associated with
elevated suicidal ideation among all CD38 genotypes, but this relationship was
stronger among individuals with the AA genotype. In contrast, there was no
relationship between the OXTR SNP, rs53576, depression or suicidal ideation.
These findings support a social sensitivity hypothesis of oxytocin, wherein the
AA genotype of the CD38 SNP, which has been considered the "protective allele"
was associated with increased sensitivity and susceptibility to disturbed social
relations and suicidal ideation.
PMID- 27486395
TI - A Comprehensive Account of Sound Sequence Imitation in the Songbird.
AB - The amazing imitation capabilities of songbirds show that they can memorize
sensory sequences and transform them into motor activities which in turn generate
the original sound sequences. This suggests that the bird's brain can learn (1)
to reliably reproduce spatio-temporal sensory representations and (2) to
transform them into corresponding spatio-temporal motor activations by using an
inverse mapping. Neither the synaptic mechanisms nor the network architecture
enabling these two fundamental aspects of imitation learning are known. We
propose an architecture of coupled neuronal modules that mimick areas in the song
bird and show that a unique synaptic plasticity mechanism can serve to learn
both, sensory sequences in a recurrent neuronal network, as well as an inverse
model that transforms the sensory memories into the corresponding motor
activations. The proposed membrane potential dependent learning rule together
with the architecture that includes basic features of the bird's brain represents
the first comprehensive account of bird imitation learning based on spiking
neurons.
PMID- 27486393
TI - Spared Primary Motor Cortex and The Presence of MEP in Cerebral Palsy Dictate the
Responsiveness to tDCS during Gait Training.
AB - The current priority of investigations involving transcranial direct current
stimulation (tDCS) and neurorehabilitation is to identify biomarkers associated
with the positive results of the interventions such that respondent and non
respondent patients can be identified in the early phases of treatment. The aims
were to determine whether: (1) present motor evoked potential (MEP); and (2)
injuries involving the primary motor cortex, are associated with tDCS-enhancement
in functional outcome following gait training in children with cerebral palsy
(CP). We reviewed the data from our parallel, randomized, sham-controlled, double
blind studies. Fifty-six children with spastic CP received gait training (either
treadmill training or virtual reality training) and tDCS (active or sham).
Univariate and multivariate logistic regression analyses were employed to
identify clinical, neurophysiologic and neuroanatomic predictors associated with
the responsiveness to treatment with tDCS. MEP presence during the initial
evaluation and the subcortical injury were associated with positive effects in
the functional results. The logistic regression revealed that present MEP was a
significant predictor for the six-minute walk test (6MWT; p = 0.003) and gait
speed (p = 0.028), whereas the subcortical injury was a significant predictor of
gait kinematics (p = 0.013) and gross motor function (p = 0.021). In this
preliminary study involving children with CP, two important prediction factors of
good responses to anodal tDCS combined with gait training were identified.
Apparently, MEP (integrity of the corticospinal tract) and subcortical location
of the brain injury exerted different influences on aspects related to gait, such
as velocity and kinematics.
PMID- 27486396
TI - Coding Properties of Mouse Retinal Ganglion Cells with Dual-Peak Patterns with
Respect to Stimulus Intervals.
AB - How visual information is encoded in spikes of retinal ganglion cells (RGCs) is
essential in visual neuroscience. In the present study, we investigated the
coding properties of mouse RGCs with dual-peak patterns with respect to visual
stimulus intervals. We first analyzed the response properties, and observed that
the latencies and spike counts of the two response peaks in the dual-peak pattern
exhibited systematic changes with the preceding light-OFF interval. We then
applied linear discriminant analysis (LDA) to assess the relative contributions
of response characteristics of both peaks in information coding regarding the
preceding stimulus interval. It was found that for each peak, the discrimination
results were far better than chance level based on either latency or spike count,
and were further improved by using the combination of the two parameters.
Furthermore, the best discrimination results were obtained when latencies and
spike counts of both peaks were considered in combination. In addition, the
correct rate for stimulation discrimination was higher when RGC population
activity was considered as compare to single neuron's activity, and the correct
rate was increased with the group size. These results suggest that rate coding,
temporal coding, and population coding are all involved in encoding the different
stimulus-interval patterns, and the two response peaks in the dual-peak pattern
carry complementary information about stimulus interval.
PMID- 27486397
TI - Handling Metadata in a Neurophysiology Laboratory.
AB - To date, non-reproducibility of neurophysiological research is a matter of
intense discussion in the scientific community. A crucial component to enhance
reproducibility is to comprehensively collect and store metadata, that is, all
information about the experiment, the data, and the applied preprocessing steps
on the data, such that they can be accessed and shared in a consistent and simple
manner. However, the complexity of experiments, the highly specialized analysis
workflows and a lack of knowledge on how to make use of supporting software tools
often overburden researchers to perform such a detailed documentation. For this
reason, the collected metadata are often incomplete, incomprehensible for
outsiders or ambiguous. Based on our research experience in dealing with diverse
datasets, we here provide conceptual and technical guidance to overcome the
challenges associated with the collection, organization, and storage of metadata
in a neurophysiology laboratory. Through the concrete example of managing the
metadata of a complex experiment that yields multi-channel recordings from
monkeys performing a behavioral motor task, we practically demonstrate the
implementation of these approaches and solutions with the intention that they may
be generalized to other projects. Moreover, we detail five use cases that
demonstrate the resulting benefits of constructing a well-organized metadata
collection when processing or analyzing the recorded data, in particular when
these are shared between laboratories in a modern scientific collaboration.
Finally, we suggest an adaptable workflow to accumulate, structure and store
metadata from different sources using, by way of example, the odML metadata
framework.
PMID- 27486394
TI - Higher Precision in Pointing Movements of the Preferred vs. Non-Preferred Hand Is
Associated with an Earlier Occurrence of Anticipatory Postural Adjustments.
AB - It is a common experience to exhibit a greater dexterity when performing a
pointing movement with the preferred limb (PREF) vs. the non-preferred (NON-PREF)
one. Here we provide evidence that the higher precision in pointing movements of
the PREF vs. NON-PREF hand is associated with an earlier occurrence of the
anticipatory postural adjustments (APAs). In this aim, we compared the APAs which
stabilize the left or the right arm when performing a pen-pointing movement
(prime mover flexor carpi radialis (FCR)). Moreover, we analyzed the elbow and
wrist kinematics as well as the precision of the pointing movement. The mean
kinematics of wrist movement and its latency, with respect to prime mover
recruitment, were similar in the two sides, while APAs in triceps brachii (TB),
biceps brachii (BB) and anterior deltoid (AD) were more anticipated when
movements were performed with the PREF than with the NON-PREF hand (60-70 vs. 20
30 ms). APAs amplitudes were comparable in the muscles of the two sides. Earlier
APAs in the preferred limb were associated with a better fixation of the elbow,
which showed a lower excursion, and with a less scattered pointing error (PREF:
10.1 +/- 0.8 mm; NON-PREF: 16.3 +/- 1.7). Present results suggest that, by
securing the more proximal joints dynamics, an appropriate timing of the intra
limb APAs is necessary for refining the voluntary movement precision, which is
known to be scarce on the NON-PREF side.
PMID- 27486398
TI - Proposed Training to Meet Challenges of Large-Scale Data in Neuroscience.
AB - The scale of data being produced in neuroscience at present and in the future
creates new and unheralded challenges, outstripping conventional ways of
handling, considering, and analyzing data. As neuroinformatics enters into this
big data era, a need for a highly trained and perhaps unique workforce is
emerging. To determine the staffing needs created by the impending era of big
data, a workshop (iNeuro Project) was convened November 13-14, 2014. Participants
included data resource providers, bioinformatics/analytics trainers, computer
scientists, library scientists, and neuroscience educators. These individuals
provided perspectives on the challenges of big data, the preparation of a
workforce to meet these challenges, and the present state of training programs.
Participants discussed whether suitable training programs will need to be
constructed from scratch or if existing programs can serve as models. Currently,
most programs at the undergraduate and graduate levels are located in Europe
participants knew of none in the United States. The skill sets that training
programs would need to provide as well as the curriculum necessary to teach them
were also discussed. Consistent with Vision and Change in Undergraduate Biology
Education: A Call to Action, proposed curricula included authentic, hands-on
research experiences. Further discussions revolved around the logistics and
barriers to creating such programs. The full white paper, iNeuro Project Workshop
Report, is available from iNeuro Project.
PMID- 27486399
TI - Mechanosensory Neuron Aging: Differential Trajectories with Lifespan-Extending
Alaskan Berry and Fungal Treatments in Caenorhabditis elegans.
AB - Many nutritional interventions that increase lifespan are also proposed to
postpone age-related declines in motor and cognitive function. Potential sources
of anti-aging compounds are the plants and fungi that have adapted to extreme
environments. We studied the effects of four commonly consumed and culturally
relevant Interior Alaska berry and fungus species (bog blueberry, lowbush
cranberry, crowberry, and chaga) on the decline in overall health and neuron
function and changes in touch receptor neuron morphology associated with aging.
We observed increased wild-type Caenorhabditis elegans lifespan and improved
markers of healthspan upon treatment with Alaskan blueberry, lowbush cranberry,
and chaga extracts. Interestingly, although all three treatments increased
lifespan, they differentially affected the development of aberrant morphologies
in touch receptor neurons. Blueberry treatments decreased anterior mechanosensory
neuron (ALM) aberrations (i.e., extended outgrowths and abnormal cell bodies)
while lowbush cranberry treatment increased posterior mechanosensory neuron (PLM)
aberrations, namely process branching. Chaga treatment both decreased ALM
aberrations (i.e., extended outgrowths) and increased PLM aberrations (i.e.,
process branching and loops). These results support the large body of knowledge
positing that there are multiple cellular strategies and mechanisms for promoting
health with age. Importantly, these results also demonstrate that although an
accumulation of abnormal neuron morphologies is associated with aging and
decreased health, not all of these morphologies are detrimental to neuronal and
organismal health.
PMID- 27486400
TI - Statistical Approaches for the Study of Cognitive and Brain Aging.
AB - Neuroimaging studies of cognitive and brain aging often yield massive datasets
that create many analytic and statistical challenges. In this paper, we discuss
and address several limitations in the existing work. (1) Linear models are often
used to model the age effects on neuroimaging markers, which may be inadequate in
capturing the potential nonlinear age effects. (2) Marginal correlations are
often used in brain network analysis, which are not efficient in characterizing a
complex brain network. (3) Due to the challenge of high-dimensionality, only a
small subset of the regional neuroimaging markers is considered in a prediction
model, which could miss important regional markers. To overcome those obstacles,
we introduce several advanced statistical methods for analyzing data from
cognitive and brain aging studies. Specifically, we introduce semiparametric
models for modeling age effects, graphical models for brain network analysis, and
penalized regression methods for selecting the most important markers in
predicting cognitive outcomes. We illustrate these methods using the healthy
aging data from the Active Brain Study.
PMID- 27486401
TI - HLA-B (*) 58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions:
Implication for Clinical Interpretation in Thailand.
AB - BACKGROUND: The aim of this study was to investigate the predisposition to
different types of allopurinol-induced cutaneous adverse drug reactions (CADR),
including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS
TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n =
10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B (*) 58:01 in a
Thai population. METHODS: This case-control association study compares 30
patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n
= 100), and a Thai general population (n = 1095). Patients' human leukocyte
antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence
specific oligonucleotide probe system. RESULTS: Of a total 30 patients with CADR
due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous
for HLA-B (*) 58:01, compared to only 4.0% in allopurinol-tolerant patients (p <
0.001). Odds ratio (OR) for the association of HLA-B (*) 58:01 with allopurinol
induced CADR in this population was 696.0 (95% CI: 74.8-6475.0). The HLA-B (*)
58:01 allele was present in all patients with allopurinol-induced SJS-TEN (OR =
579.0, 95%CI: 29.5-11362.7, p < 0.001) and DRESS (OR 430.3, 95%CI: 22.6-8958.9, p
< 0.001). Additionally, OR of HLA-B (*) 58:01 was highly significant in the
allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9-1497.0, p < 0.001).
CONCLUSION: In this study we confirmed the association between HLAB (*) 58:01 and
allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an
association between HLA-B (*) 58:01 and allopurinol-induced DRESS and MPE in this
population. Therefore, HLA-B (*) 58:01 can be used as a pharmacogenetic marker
for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results
suggest that screening for HLA-B (*) 58:01 alleles in patients who will be
treated with allopurinol would be clinically helpful in preventing the risk of
developing CARD in a Thai patients. Summary Regardless of phenotype, this is the
first pharmacogenetic study of allopurinol-induced CADR in patients of Thai
ancestry.In this study we confirmed the association between HLA-B (*) 58:01 and
allopurinol-induced SJS-TEN, DRESS, and MPE in Thai population.Regarding to our
findings, the pharmacogenetic interpretation could be generalized to drug
hypersensitivity including DRESS, SJS-TEN, and MPE.
PMID- 27486402
TI - Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.
AB - Orthodontic forces disturb the microenvironment of the periodontal ligament
(PDL), and induce craniofacial bone remodeling which is necessary for tooth
movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic
injury and cell death within the PDL (hyalinization) and root resorption. Large
inter-individual differences in hyalinization and root resorption have been
observed, and may be explained by differential protection against hyalinization.
Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down
heme into the strong anti-oxidants biliverdin/bilirubin and the signaling
molecule carbon monoxide. These versatile HO-1 products protect against ischemic
and inflammatory injury. We postulate that orthodontic forces induce HO-1
expression in the PDL during experimental tooth movement. Twenty-five 6-week-old
male Wistar rats were used in this study. The upper three molars at one side were
moved mesially using a Nickel-Titanium coil spring, providing a continuous
orthodontic force of 10 cN. The contralateral side served as control. After 6,
12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections
immunohistochemical staining was performed for analysis of HO-1 expression and
quantification of osteoclasts. Orthodontic force induced a significant time
dependent HO-1 expression in mononuclear cells within the PDL at both the
apposition- and resorption side. Shortly after placement of the orthodontic
appliance HO-1 expression was highly induced in PDL cells but dropped to control
levels within 72 h. Some osteoclasts were also HO-1 positive but this induction
was shown to be independent of time- and mechanical stress. It is tempting to
speculate that differential induction of tissue protecting- and osteoclast
activating genes in the PDL determine the level of bone resorption and
hyalinization and, subsequently, "fast" and "slow" tooth movers during
orthodontic treatment.
PMID- 27486403
TI - Cloning, Characteristics, and Functional Analysis of Rabbit NADPH Oxidase 5.
AB - BACKGROUND: Nox5 was the last member of the Nox enzyme family to be identified.
Functionally distinct from the other Nox isoforms, our understanding of its
physiological significance has been hampered by the absence of Nox5 in mouse and
rat genomes. Nox5 is present in the genomes of other species such as the rabbit
that have broad utility as models of cardiovascular disease. However, the mRNA
sequence, characteristics, and functional analysis of rabbit Nox5 has not been
fully defined and were the goals of the current study. METHODS: Rabbit Nox5 was
amplified from rabbit tissue, cloned, and sequenced. COS-7 cells were employed
for expression and functional analysis via Western blotting and measurements of
superoxide. We designed and synthesized miRNAs selectively targeting rabbit Nox5.
The nucleotide and amino acid sequences of rabbit Nox5 were aligned with those of
putative rabbit isoforms (X1, X2, X3, and X4). A phylogenetic tree was generated
based on the mRNA sequence for Nox5 from rabbit and other species. RESULTS:
Sequence alignment revealed that the identified rabbit Nox5 was highly conserved
with the predicted sequence of rabbit Nox5. Cell based experiments reveal that
rabbit Nox5 was robustly expressed and produced superoxide at rest and in a
calcium and PMA-dependent manner that was susceptible to superoxide dismutase and
the flavoprotein inhibitor, DPI. miRNA-1 was shown to be most effective in down
regulating the expression of rabbit Nox5. Phylogenetic analysis revealed a close
relationship between rabbit and armadillo Nox5. Rabbit Nox5 was relatively
closely related to human Nox5, but lies in a distinct cluster. CONCLUSION: Our
study establishes the suitability of the rabbit as a model organism to further
our understanding of the role of Nox5 in cardiovascular and other diseases and
provides new information on the genetic relationship of Nox5 genes in different
species.
PMID- 27486404
TI - Fast Regulation of Vertical Squat Jump during Push-Off in Skilled Jumpers.
AB - The height of a maximum Vertical Squat Jump (VSJ) reflects the useful power
produced by a jumper during the push-off phase. In turn this partly depends on
the coordination of the jumper's segmental rotations at each instant. The
physical system constituted by the jumper has been shown to be very sensitive to
perturbations and furthermore the movement is realized in a very short time (ca.
300 ms), compared to the timing of known feedback loops. However, the dynamics of
the segmental coordination and its efficiency in relation to energetics at each
instant of the push-off phase still remained to be clarified. Their study was the
main purpose of the present research. Eight young adult volunteers (males)
performed maximal VSJ. They were skilled in jumping according to their sport
activities (track and field or volleyball). A video analysis on the kinematics of
the jump determined the influence of the jumpers' segments rotation on the
vertical velocity and acceleration of the body mass center (MC). The efficiency
in the production of useful power at the jumpers' MC level, by the rotation of
the segments, was measured in consequence. The results showed a great variability
in the segmental movements of the eight jumpers, but homogeneity in the overall
evolution of these movements with three consecutive types of coordination in the
second part of the push-off (lasting roughly 0.16 s). Further analyses gave
insights on the regulation of the push-off, suggesting that very fast
regulation(s) of the VSJ may be supported by: (a) the adaptation of the motor
cerebral programming to the jumper's physical characteristics; (b) the control of
the initial posture; and
PMID- 27486405
TI - Altered Differential Control of Sympathetic Outflow Following Sedentary
Conditions: Role of Subregional Neuroplasticity in the RVLM.
AB - Despite the classically held belief of an "all-or-none" activation of the
sympathetic nervous system, differential responses in sympathetic nerve activity
(SNA) can occur acutely at varying magnitudes and in opposing directions.
Sympathetic nerves also appear to contribute differentially to various disease
states including hypertension and heart failure. Previously we have reported that
sedentary conditions enhanced responses of splanchnic SNA (SSNA) but not lumbar
SNA (LSNA) to activation of the rostral ventrolateral medulla (RVLM) in rats.
Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic
branching in rostral regions of the RVLM. We hypothesized that regionally
specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA
following activation of the rostral RVLM. To test this hypothesis, groups of
physically active (10-12 weeks on running wheels) or sedentary, male Sprague
Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA
under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM)
into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not
LSNA responses and SSNA responses were enhanced at more central and rostral
sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with
enhanced dendritic branching in rostral RVLM observed previously. Identifying
structural and functional neuroplasticity in specific populations of RVLM neurons
may help identify new treatments for cardiovascular diseases, known to be more
prevalent in sedentary individuals.
PMID- 27486406
TI - A Guide to Transient Expression of Membrane Proteins in HEK-293 Cells for
Functional Characterization.
AB - The human embryonic kidney 293 (HEK-293) cells are commonly used as host for the
heterologous expression of membrane proteins not least because they have a high
transfection efficiency and faithfully translate and process proteins. In
addition, their cell size, morphology and division rate, and low expression of
native channels are traits that are particularly attractive for current-voltage
measurements. Nevertheless, the heterologous expression of complex membrane
proteins such as receptors and ion channels for biological characterization and
in particular for single-cell applications such as electrophysiology remains a
challenge. Expression of functional proteins depends largely on careful step-by
step optimization that includes the design of expression vectors with suitable
identification tags, as well as the selection of transfection methods and
detection parameters appropriate for the application. Here, we use the
heterologous expression of a plant potassium channel, the Arabidopsis thaliana
guard cell outward-rectifying K(+) channel, AtGORK (At5G37500) in HEK-293 cells
as an example, to evaluate commonly used transfection reagents and fluorescent
detection methods, and provide a detailed methodology for optimized transient
transfection and expression of membrane proteins for in vivo studies in general
and for single-cell applications in particular. This optimized protocol will
facilitate the physiological and cellular characterization of complex membrane
proteins.
PMID- 27486407
TI - Ectotherms in Variable Thermal Landscapes: A Physiological Evaluation of the
Invasive Potential of Fruit Flies Species.
AB - Climate change and biological invasions pose one of the greatest threats to
biodiversity. Most analyses of the potential biological impacts have focused on
changes in mean temperature, but changes in thermal variance may also impact
native and invasive organisms, although differentially. We assessed the combined
effects of the mean and the variance of temperature on the expression of heat
shock protein (hsp90) in adults of the invasive fruit fly Drosophila melanogaster
and the native Drosophila gaucha in Mediterranean habitats of central Chile. We
observed that, under these experimental conditions, hsp90 mRNA expression was
higher in the invasive species but absent in the native one. Apparently, the
biogeographic origin and niche conservatisms are playing a role in the heat shock
response of these species under different putative scenarios of climate change.
We suggest that in order to develop more realistic predictions about the
biological impact of climate change and biological invasions, one must consider
the interactions between the mean and variance of climatic variables, as well as
the evolutionary original conditions of the native and invasive species.
PMID- 27486408
TI - Cognitive Neuroscience and Causal Inference: Implications for Psychiatry.
AB - In this paper, we investigate to what extent it is justified to draw conclusions
about causal relations between brain states and mental states from cognitive
neuroscience studies. We first explain the views of two prominent proponents of
the interventionist account of causation: Woodward and Baumgartner. We then
discuss the implications of their views in the context of traditional cognitive
neuroscience studies in which the effect of changes in mental state on changes in
brain states is investigated. After this, we turn to brain stimulation studies in
which brain states are manipulated to investigate the effects on mental states.
We argue that, depending on whether one sides with Woodward or Baumgartner, it is
possible to draw causal conclusions from both types of studies (Woodward) or from
brain stimulation studies only (Baumgartner). We show what happens to these
conclusions if we adopt different views of the relation between mental states and
brain states. Finally, we discuss the implications of our findings for psychiatry
and the treatment of psychiatric disorders.
PMID- 27486409
TI - Imitated Prosodic Fluency Predicts Reading Comprehension Ability in Good and Poor
High School Readers.
AB - Researchers have established a relationship between beginning readers' silent
comprehension ability and their prosodic fluency, such that readers who read
aloud with appropriate prosody tend to have higher scores on silent reading
comprehension assessments. The current study was designed to investigate this
relationship in two groups of high school readers: Specifically Poor
Comprehenders (SPCs), who have adequate word level and phonological skills but
poor reading comprehension ability, and a group of age- and decoding skill
matched controls. We compared the prosodic fluency of the two groups by
determining how effectively they produced prosodic cues to syntactic and semantic
structure in imitations of a model speaker's production of syntactically and
semantically varied sentences. Analyses of pitch and duration patterns revealed
that speakers in both groups produced the expected prosodic patterns; however,
controls provided stronger durational cues to syntactic structure. These results
demonstrate that the relationship between prosodic fluency and reading
comprehension continues past the stage of early reading instruction. Moreover,
they suggest that prosodically fluent speakers may also generate more fluent
implicit prosodic representations during silent reading, leading to more
effective comprehension.
PMID- 27486410
TI - Do Our Means of Inquiry Match our Intentions?
AB - A key stage of the scientific method is the analysis of data, yet despite the
variety of methods that are available to researchers they are most frequently
distilled to a model that focuses on the average relation between variables.
Although research questions are frequently conceived with broad inquiry in mind,
most regression methods are limited in comprehensively evaluating how observed
behaviors are related to each other. Quantile regression is a largely unknown yet
well-suited analytic technique similar to traditional regression analysis, but
allows for a more systematic approach to understanding complex associations among
observed phenomena in the psychological sciences. Data from the National
Education Longitudinal Study of 1988/2000 are used to illustrate how quantile
regression overcomes the limitations of average associations in linear regression
by showing that psychological well-being and sex each differentially relate to
reading achievement depending on one's level of reading achievement.
PMID- 27486411
TI - The Feeling of "Face" in Confucian Society: From a Perspective of Psychosocial
Equilibrium.
AB - Previous research on the feeling of "face" has long described "face" as a
complicated phenomenon in Confucian societies. Indeed, the feeling of face is
highly context dependent. One may have very different (having or losing) face
perception if the same face event occurs in a different context. To better
capture the features of how face is felt, effects on possible responses need to
be considered. Therefore, this article adopts a perspective of psychosocial
equilibrium to elaborate people's feeling of face in Taiwan, a Confucian society.
The first section illustrates the concept of psychosocial equilibrium and its
psychodynamic effects on people's feeling of face. Then, the second section of
this article takes positive social situations (having face events) as backdrop to
exhibit how people balance their psychosocial equilibrium with different
relationships. Following the positive social situations, the third section of
this article then focuses on the negative situations (losing face events) to
explain how losing face is felt due to unbalance of psychosocial equilibrium with
one's relation in that specific context.
PMID- 27486412
TI - Familiality of Co-existing ADHD and Tic Disorders: Evidence from a Large Sibling
Study.
AB - BACKGROUND: The association of attention-deficit/hyperactivity disorder (ADHD)
and tic disorder (TD) is frequent and clinically important. Very few and
inconclusive attempts have been made to clarify if and how the combination of
ADHD+TD runs in families. AIM: To determine the first time in a large-scale ADHD
sample whether ADHD+TD increases the risk of ADHD+TD in siblings and, also the
first time, if this is independent of their psychopathological vulnerability in
general. METHODS: The study is based on the International Multicenter ADHD
Genetics (IMAGE) study. The present sub-sample of 2815 individuals included ADHD
index patients with co-existing TD (ADHD+TD, n = 262) and without TD (ADHD-TD, n
= 947) as well as their 1606 full siblings (n = 358 of the ADHD+TD index patients
and n = 1248 of the ADHD-TD index patients). We assessed psychopathological
symptoms in index patients and siblings by using the Strength and Difficulties
Questionnaire (SDQ) and the parent and teacher Conners' long version Rating
Scales (CRS). For disorder classification the Parental Account of Childhood
Symptoms (PACS-Interview) was applied in n = 271 children. Odds ratio with the
GENMOD procedure (PROCGENMOD) was used to test if the risk for ADHD, TD, and
ADHD+TD in siblings was associated with the related index patients' diagnoses. In
order to get an estimate for specificity we compared the four groups for general
psychopathological symptoms. RESULTS: Co-existing ADHD+TD in index patients
increased the risk of both comorbid ADHD+TD and TD in the siblings of these index
patients. These effects did not extend to general psychopathology.
INTERPRETATION: Co-existence of ADHD+TD may segregate in families. The same holds
true for TD (without ADHD). Hence, the segregation of TD (included in both
groups) seems to be the determining factor, independent of further behavioral
problems. This close relationship between ADHD and TD supports the clinical
approach to carefully assess ADHD in any case of TD.
PMID- 27486413
TI - Untangling the Contribution of the Subcomponents of Working Memory to
Mathematical Proficiency as Measured by the National Tests: A Study among Swedish
Third Graders.
AB - The aim with the present study was to examine the relationship between the
subcomponents in working memory (WM) and mathematical performance, as measured by
the National tests in a sample of 597 Swedish third-grade pupils. In line with
compelling evidence of other studies, individual differences in WM capacity
significantly predicted mathematical performance. Dividing the sample into four
groups, based on their mathematical performance, revealed that mathematical
ability can be conceptualized in terms of different WM profiles. Pupils
categorized as High-math performers particularly differed from the other three
groups in having a significant higher phonological ability. In contrast, pupils
categorized as Low-math performers were particularly characterized by having a
significant lower visuo-spatial ability. Findings suggest that it is important
for educators to recognize and acknowledge individual differences in WM to
support mathematical achievement at an individual level.
PMID- 27486414
TI - Get Your Facts Right: Preschoolers Systematically Extend Both Object Names and
Category-Relevant Facts.
AB - There is an ongoing debate over the extent to which language development shares
common processing mechanisms with other domains of learning. It is well
established that toddlers will systematically extend object labels to similarly
shaped category exemplars (e.g., Markman and Hutchinson, 1984; Landau et al.,
1988). However, previous research is inconclusive as to whether young children
will similarly extend factual information about an object to other category
members. We explicitly contrast facts varying in category relevance, and test for
extension using two different tasks. Three- to four-year-olds (N = 61) were
provided with one of three types of information about a single novel object: a
category-relevant fact ('it's from a place called Modi'), a category-irrelevant
fact ('my uncle gave it to me'), or an object label ('it's called a Modi'). At
test, children provided with the object name or category-relevant fact were
significantly more likely to display systematic category extension than children
who learnt the category-irrelevant fact. Our findings contribute to a growing
body of evidence that the mechanisms responsible for word learning may be domain
general in nature.
PMID- 27486416
TI - Can We Talk through a Robot As if Face-to-Face? Long-Term Fieldwork Using
Teleoperated Robot for Seniors with Alzheimer's Disease.
AB - This work presents a case study on fieldwork in a group home for the elderly with
dementia using a teleoperated robot called Telenoid. We compared Telenoid
mediated and face-to-face conditions with three residents with Alzheimer's
disease (AD). The result indicates that two of the three residents with moderate
AD showed a positive reaction to Telenoid. Both became less nervous while
communicating with Telenoid from the time they were first introduced to it.
Moreover, they started to use more body gestures in the face-to-face condition
and more physical interactions in the Telenoid-mediated condition. In this work,
we present all the results and discuss the possibilities of using Telenoid as a
tool to provide opportunities for seniors to communicate over the long term.
PMID- 27486415
TI - Bayesian Analysis of Individual Level Personality Dynamics.
AB - A Bayesian technique with analyses of within-person processes at the level of the
individual is presented. The approach is used to examine whether the patterns of
within-person responses on a 12-trial simulation task are consistent with the
predictions of ITA theory (Dweck, 1999). ITA theory states that the performance
of an individual with an entity theory of ability is more likely to spiral down
following a failure experience than the performance of an individual with an
incremental theory of ability. This is because entity theorists interpret failure
experiences as evidence of a lack of ability which they believe is largely innate
and therefore relatively fixed; whilst incremental theorists believe in the
malleability of abilities and interpret failure experiences as evidence of more
controllable factors such as poor strategy or lack of effort. The results of our
analyses support ITA theory at both the within- and between-person levels of
analyses and demonstrate the benefits of Bayesian techniques for the analysis of
within-person processes. These include more formal specification of the theory
and the ability to draw inferences about each individual, which allows for more
nuanced interpretations of individuals within a personality category, such as
differences in the individual probabilities of spiraling. While Bayesian
techniques have many potential advantages for the analyses of processes at the
level of the individual, ease of use is not one of them for psychologists trained
in traditional frequentist statistical techniques.
PMID- 27486417
TI - The Association among Difficulties in Emotion Regulation, Hostility, and Empathy
in a Sample of Young Italian Adults.
AB - The aim of the present study was to assess the role of empathy in mediating the
association between difficulties in emotion regulation and hostility. Three
hundred and sixty young Italian adults (220 women and 140 men) were enrolled in
the study. Psychopathological assessments included the Difficulties in Emotion
Regulation Scale (DERS), the Interpersonal Reactivity Index and the Buss-Durkee
Hostility Inventory (BDHI). Perspective taking (PT) and Personal distress (PD)
are significantly associated with both DERS total score and BDHI total score. A
mediational model analyzing the direct and indirect effects of DERS on BDHI
through the mediating role of PT and PD showed that the relation between DERS and
BDHI was partially mediated by PT total score (b = 0.16; se = 0.01; p = 0.02).
Taken together our findings support the possibility that PT skills could play a
crucial role in inhibiting hostility behaviors.
PMID- 27486418
TI - The Experience of Depression during the Careers of Elite Male Athletes.
AB - The topic of depression during the career of elite male athletes has been the
subject of much public interest and attention in recent years. Despite numerous
debates and personal disclosures within the media, there is a dearth of published
research directly exploring the phenomenon. This study sought to explore how
elite male athletes experience depression during their sporting careers. Eight
former/current elite male athletes who had previously publically self-identified
as having experienced depression while participating in sport were recruited for
this study. A qualitative methodology was employed and each participant was
interviewed using semi-structured interviews. Data analysis which was conducted
using descriptive and interpretive thematic analysis uncovered three domains: (1)
The emergence of depression, (2) The manifestation of symptoms of depression, and
(3) Adaptive and Maladaptive proceesses of recovery. Findings from the current
study reveal the nature of how male athletes experience, express, and respond to
depression during their careers. Additionally, this is influenced by a myriad of
factors embedded in the masculine elite sport environment. Implications are
discussed particularly in relation to atypical expressions of depression not
necessarily reflected on or in standard diagnostic criteria. Future research is
encouraged to examine in depth moderating factors (e.g., athletic sense of
identity and masculine elite sport environments) for the relationship between
depression and participation in elite sport.
PMID- 27486420
TI - A Multidisciplinary Approach to Research in Small-Scale Societies: Studying
Emotions and Facial Expressions in the Field.
AB - Although cognitive science was multidisciplinary from the start, an under
emphasis on anthropology has left the field with limited research in small scale,
indigenous societies. Neglecting the anthropological perspective is risky, given
that once-canonical cognitive science findings have often been shown to be
artifacts of enculturation rather than cognitive universals. This imbalance has
become more problematic as the increased use of Western theory-driven approaches,
many of which assume human uniformity ("universality"), confronts the absence of
a robust descriptive base that might provide clarifying or even contrary
evidence. We highlight the need for remedies to such shortcomings by suggesting a
two-fold methodological shift. First, studies conducted in indigenous societies
can benefit by relying on multidisciplinary research groups to diminish
ethnocentrism and enhance the quality of the data. Second, studies devised for
Western societies can readily be adapted to the changing settings encountered in
the field. Here, we provide examples, drawn from the areas of emotion and facial
expressions, to illustrate potential solutions to recurrent problems in enhancing
the quality of data collection, hypothesis testing, and the interpretation of
results.
PMID- 27486419
TI - Can We Predict Burnout among Student Nurses? An Exploration of the ICWR-1 Model
of Individual Psychological Resilience.
AB - The nature of nursing work is demanding and can be stressful. Previous studies
have shown a high rate of burnout among employed nurses. Recently, efforts have
been made to understand the role of resilience in determining the psychological
adjustment of employed nurses. A theoretical model of resilience was proposed
recently that includes several constructs identified in the literature related to
resilience and to psychological functioning. As nursing students are the future
of the nursing workforce it is important to advance our understanding of the
determinants of resilience in this population. Student nurses who had completed
their final practicum were invited to participate in an online survey measuring
the key constructs of the ICWR-1 model. 422 students from across Australia and
Canada completed the survey between July 2014 and July 2015. As well as several
key demographics, trait negative affect, mindfulness, self-efficacy, coping,
resilience, and burnout were measured. We used structural equation modeling and
found support for the major pathways of the model; namely that resilience had a
significant influence on the relationship between mindfulness, self-efficacy and
coping, and psychological adjustment (burnout scores). Furthermore, as predicted,
Neuroticism moderated the relationship between coping and burnout. Results are
discussed in terms of potential approaches to supporting nursing students who may
be at risk of burnout.
PMID- 27486421
TI - Young Children Learning from Touch Screens: Taking a Wider View.
AB - Touch screen devices such as smartphones and tablets are now ubiquitous in the
lives of American children. These devices permit very young children to engage
interactively in an intuitive fashion with actions as simple as touching, swiping
and pinching. Yet, we know little about the role these devices play in very young
children's lives or their impact on early learning and development. Here we focus
on two areas in which existing research sheds some light on these issues with
children under 3 years of age. The first measures transfer of learning, or how
well children use information learned from screens to reason about events off
screen, using object retrieval and word learning tasks. The second measures the
impact of interactive screens on parent-child interactions and story
comprehension during reading time. More research is required to clarify the
pedagogical potential and pitfalls of touch screens for infants and very young
children, especially research focused on capabilities unique to touch screens and
on the social and cultural contexts in which young children use them.
PMID- 27486422
TI - The Impact of Early Bilingualism on Face Recognition Processes.
AB - Early linguistic experience has an impact on the way we decode audiovisual speech
in face-to-face communication. The present study examined whether differences in
visual speech decoding could be linked to a broader difference in face
processing. To identify a phoneme we have to do an analysis of the speaker's face
to focus on the relevant cues for speech decoding (e.g., locating the mouth with
respect to the eyes). Face recognition processes were investigated through two
classic effects in face recognition studies: the Other-Race Effect (ORE) and the
Inversion Effect. Bilingual and monolingual participants did a face recognition
task with Caucasian faces (own race), Chinese faces (other race), and cars that
were presented in an Upright or Inverted position. The results revealed that
monolinguals exhibited the classic ORE. Bilinguals did not. Overall, bilinguals
were slower than monolinguals. These results suggest that bilinguals' face
processing abilities differ from monolinguals'. Early exposure to more than one
language may lead to a perceptual organization that goes beyond language
processing and could extend to face analysis. We hypothesize that these
differences could be due to the fact that bilinguals focus on different parts of
the face than monolinguals, making them more efficient in other race face
processing but slower. However, more studies using eye-tracking techniques are
necessary to confirm this explanation.
PMID- 27486424
TI - Editorial: Color Vision Sensation and Perception.
PMID- 27486423
TI - Affective Norms for 4900 Polish Words Reload (ANPW_R): Assessments for Valence,
Arousal, Dominance, Origin, Significance, Concreteness, Imageability and, Age of
Acquisition.
AB - In studies that combine understanding of emotions and language, there is growing
demand for good-quality experimental materials. To meet this expectation, a large
number of 4905 Polish words was assessed by 400 participants in order to provide
a well-established research method for everyone interested in emotional word
processing. The Affective Norms for Polish Words Reloaded (ANPW_R) is designed as
an extension to the previously introduced the ANPW dataset and provides
assessments for eight different affective and psycholinguistic measures of
Valence, Arousal, Dominance, Origin, Significance, Concreteness, Imageability,
and subjective Age of Acquisition. The ANPW_R is now the largest available
dataset of affective words for Polish, including affective scores that have not
been measured in any other dataset (concreteness and age of acquisition scales).
Additionally, the ANPW_R allows for testing hypotheses concerning dual-mind
models of emotion and activation (origin and subjective significance scales).
Participants in the current study assessed all 4905 words in the list within 1
week, at their own pace in home sessions, using eight different Self-assessment
Manikin (SAM) scales. Each measured dimension was evaluated by 25 women and 25
men. The ANPW_R norms appeared to be reliable in split-half estimation and
congruent with previous normative studies in Polish. The quadratic relation
between valence and arousal was found to be in line with previous findings. In
addition, nine other relations appeared to be better described by quadratic
instead of linear function. The ANPW_R provides well-established research
materials for use in psycholinguistic and affective studies in Polish-speaking
samples.
PMID- 27486425
TI - Study Protocol on Ecological Momentary Assessment of Health-Related Quality of
Life Using a Smartphone Application.
AB - Health-Related Quality of Life (HRQoL) is a construct of increasing importance in
modern healthcare, and has typically been assessed using retrospective
instruments. While such measures have been shown to have predictive utility for
clinical outcomes, several cognitive biases associated with human recall and
current mood state may undermine their validity and reliability. Retrospective
tools can be further criticized for their lack of ecology, as individuals are
usually assessed in less natural settings such as hospitals and health centers,
and may be obliged to spend time and money traveling to receive assessment.
Ecological momentary assessment (EMA) is an alternative, as mobile assessment
using mobile health (mHealth) technology has the potential to minimize biases and
overcome many of these limitations. Employing an EMA methodology, we will use a
smartphone application to collect data on real-time HRQoL, with an adapted
version of the widely used WHOQOL-BREF questionnaire. We aim to recruit a total
of 450 healthy participants. Participants will be prompted by the application to
report their real-time HRQoL over 2 weeks together with information on mood and
current activities. At the end of 2 weeks, they will complete a retrospective
assessment of their HRQoL and they will provide information about their sleep
quality and perceived stress. The psychometric properties of real-time HRQoL will
be assessed, including analysis of the factorial structure, reliability and
validity of the measure, and compared with retrospective HRQoL responses for the
same 2-week testing period. Further, we aim to identify factors associated with
real-time HRQoL (e.g., mood, activities), the feasibility of the application, and
within- and between-person variability in real-time HRQoL. We expect real-time
HRQoL to have adequate validity and reliability, and positive responses on the
feasibility of using a smartphone application for routine HRQoL assessment. The
direct comparison of real-time and retrospective measures in this study will
provide important novel insight into the efficacy of mHealth applications for
HRQoL assessment. If shown to be valid, reliable and feasible for the collection
of HRQoL data, mHealth applications may have future potential for facilitating
clinical assessment, patient-physician communication, and monitoring individual
HRQoL over course of treatment.
PMID- 27486427
TI - The Causal Effect of Student Mobility on Standardized Test Performance: A Case
Study with Possible Implications for Accountability Mandates within the
Elementary and Secondary Education Act.
AB - This paper presents a limited case study examining the causal inference of
student mobility on standardized test performance, within one middle-class high
school in suburban Connecticut. Administrative data were used from a district
public high school enrolling 319 10th graders in 2010. Propensity score methods
were used to estimate the causal effect of student mobility on Math, Science,
Reading, and Writing portions of the Connecticut Academic Performance Test
(CAPT), after matching mobile vs. stable students on gender, race/ethnicity,
eligibility for free/reduced lunches, and special education status. Analyses
showed that mobility was associated with lower performance in the CAPT Writing
exam. Follow-up analyses revealed that this trend was only significant among
those who were ineligible for free/reduced lunches, but not among eligible
students. Additionally, mobile students who were ineligible for free/reduced
lunches had lower performance in the CAPT Science exam according to some
analyses. Large numbers of students transferring into a school district may
adversely affect standardized test performance. This is especially relevant for
policies that affect student mobility in schools, given the accountability
measures in the No Child Left Behind that are currently being re-considered in
the recent Every Student Succeeds Act.
PMID- 27486426
TI - Subjective Social Status and Cardiovascular Reactivity: An Experimental
Examination.
AB - The present experiment examined the causal influence of subjective social status
(SSS) on variables related to cardiovascular health [i.e., blood pressure, heart
rate variability (HRV)]. Participants were randomly assigned to one of two
conditions involving a social comparison that either induced a temporary shift
toward high SSS or toward low SSS. Cardiovascular variables were measured before
(baseline), throughout, and after the manipulation (recovery). Participants in
the low SSS condition had a significantly lower HRV during experimental
manipulation than at baseline (p = 0.001). They also showed a significantly
stronger HRV reactivity compared to participants in the high SSS condition (p =
0.027). Our results suggest that already temporary shifts of one's SSS have
measureable effects on cardiovascular variables. They support the notion that
social status plays a causal role in the development of cardiovascular disease.
PMID- 27486428
TI - Bringing Formal and Informal Reasoning Together-A New Era of Assessment?
PMID- 27486429
TI - The Emergence of Tool Use in Preterm Infants.
AB - Preterm born children without neurological impairments have been shown to present
some visual-manual coordination deficits, more or less depending on their
tonicity and the degree of prematurity. In this paper, we compare the development
of tool use in 15-23-month-old preterm infants born after 33-36 weeks of
gestation without neurological complications with that of full-term infants
according to corrected age. Understanding the affordance of a tool is an
important cognitive milestone in early sensorimotor period. Using a tool to bring
within reach an out-of-reach object, for instance, has been shown to develop
during the 2nd year in full-term infants. Here we presented preterm infants with
an attractive toy out of reach and with a rake-like tool within reach in five
conditions of spatial relationships between the toy and the tool. Like full
terms, preterm infants used the tool with success in conditions of spatial
contiguity around 15-17 months. In conditions of a spatial gap between tool and
toy, i.e., the only conditions which shows without ambiguity that the infant
understands the affordance of the tool, preterm infants as a group showed no
delay for tool use: the frequency of spontaneous successes started to increase
after 18 months, and demonstration became effective after that age. However,
further analyses showed that only the preterm infants without hypotonia and born
after 36 weeks of pregnancy developed tool use without delay. Hypotonic preterm
infants were still largely unsuccessful in the conditions of spatial gap, even at
the end of the study. The degree of prematurity also influenced the performance
at tool use. These results, following the observation of a delay in the
development of bimanual coordination and of handedness in the same infants at 10
12 months in a previous study, show that low risk preterm infants can still be
impaired for the development of new manual skills beyond the 1st year. Thus,
hypotonic preterm infants and infants born before 36 weeks of pregnancy should be
followed and might benefit from early intervention programs.
PMID- 27486430
TI - Aging Increases Compensatory Saccade Amplitude in the Video Head Impulse Test.
AB - OBJECTIVE: Rotational vestibular function declines with age resulting in saccades
as a compensatory mechanism to improve impaired gaze stability. Small reductions
in rotational vestibulo-ocular reflex (VOR) gain that would be considered
clinically normal have been associated with compensatory saccades. We evaluated
whether compensatory saccade characteristics varied as a function of age,
independent of semicircular canal function as quantified by VOR gain. METHODS:
Horizontal VOR gain was measured in 243 participants age 27-93 from the Baltimore
Longitudinal Study of Aging using video head impulse testing. Latency and
amplitude of the first saccade (either covert - occurring during head impulse, or
overt - occurring following head impulse) were measured for head impulses with
compensatory saccades (n = 2230 head impulses). The relationship between age and
saccade latency, as well as the relationship between age and saccade amplitude,
were evaluated using regression analyses adjusting for VOR gain, gender, and
race. RESULTS: Older adults (mean age 75.9) made significantly larger
compensatory saccades relative to younger adults (mean age 45.0). In analyses
adjusted for VOR gain, there was a significant association between age and
amplitude of the first compensatory covert saccade (beta = 0.015, p = 0.008). In
analyses adjusted for VOR gain, there was a significant association between age
and amplitude of the first compensatory overt saccade (beta = 0.02, p < 0.001).
Compensatory saccade latencies did not vary significantly by age. CONCLUSION: We
observed that aging increases the compensatory catch-up saccade amplitude in
healthy adults after controlling for VOR gain. Size of compensatory saccades may
be useful in addition to VOR gain for characterizing vestibular function in aging
adults.
PMID- 27486431
TI - Intrusive Thoughts Elicited by Direct Electrical Stimulation during Stereo
Electroencephalography.
AB - Cortical direct electrical stimulation (DES) is a method of brain mapping used
during invasive presurgical evaluation of patients with intractable epilepsy.
Intellectual auras like intrusive thoughts, also known as forced thinking (FT),
have been reported during frontal seizures. However, there are few reports on FT
obtained during DES in frontal cortex. We report three cases in which we obtained
intrusive thoughts while stimulating the dorsolateral prefrontal cortex and the
white matter in the prefrontal region. In order to highlight the effective
connectivity that might explain this clinical response, we have analyzed cortico
cortical potentials evoked by single pulse electrical stimulation.
PMID- 27486433
TI - Association Studies of the GPR103 and BCL2L15 Genes in Autoimmune Thyroid Disease
in the Japanese Population.
AB - While the past genome-wide association study (GWAS) for autoimmune thyroid
diseases (AITDs) was done in Caucasians, a recent GWAS in Caucasian patients with
both AITD and type 1 diabetes [a variant of autoimmune polyglandular syndrome
type 3 (APS3v)] identified five non-HLA genes: BCL2L15, MAGI3, PHTF1, PTPN22, and
GPR103. The aim of our study was to replicate these associations with AITD in a
Japanese population. Since analyzing the rs2476601 single-nucleotide polymorphism
(SNP) within the PTPN22 gene revealed no polymorphism in the Japanese, we
analyzed four SNPs, rs2358994 (in BCL2L15), rs2153977 (in MAGI3), rs1111695 (in
PHTF1), and rs7679475 (in GPR103) genotypes in a case-control study based on 447
Japanese AITD patients [277 Graves' disease (GD) and 170 Hashimoto's thyroiditis
(HT) patients] and 225 matched Japanese controls using the high-resolution
melting and unlabeled probe methods. Case-control association studies were
performed using the chi(2) and Fisher's exact tests with Yates correction. The G
allele of rs7679475 (A/G) was associated with HT compared with controls [P =
0.022, odds ratio (OR) = 0.69]. GD showed no significant associations with any
SNPs. However, when patients with GD were stratified according to Graves'
ophthalmopathy (GO), the G allele of rs2358994 (A/G) was associated with GO vs.
controls (P = 0.018, OR = 1.52). These findings suggest that in the Japanese
population the GPR103 gene may contribute to the pathogenesis of HT. Moreover,
this study demonstrated that the SNP rs2358994 within BCL2L15 gene is associated
with GO in the Japanese population.
PMID- 27486432
TI - An Abbreviated Diagnostic Maneuver for Posterior Benign Positional Paroxysmal
Vertigo.
AB - INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) secondary to
canalolithiasis of the posterior semicircular canal is perhaps the most frequent
cause of vertigo and dizziness. One of its properties is a high response rate to
canalith repositioning maneuvers. However, delays in the diagnosis and treatment
of this entity can range from days to years, depending on the setting. Here, we
present an abbreviated variation of the Dix-Hallpike maneuver, which can be used
to diagnose this disease. It is similar to the standard maneuver but can be
performed without an examination bed/table and requires only a backed chair (a
difference that we feel is very important in settings where a clinical bed/table
is not readily available). METHODS: A diagnostic assessment study was conducted
in 163 patients who presented with vertigo or dizziness. RESULTS: The abbreviated
test had fairly good sensitivity (80%) and high specificity (95%) for diagnosing
posterior BPPV. DISCUSSION: This new diagnostic maneuver may serve as a screening
procedure for quickly identifying this pathology. This will allow patients to be
more directly treated, without requiring unnecessary referrals or full vestibular
testing, and will be especially useful in primary care settings or heavily
overloaded otolaryngology or neurology departments.
PMID- 27486434
TI - Statin Therapy Alters Lipid Storage in Diabetic Skeletal Muscle.
AB - While statins significantly reduce cholesterol levels and thereby reduce the risk
of cardiovascular disease, the development of myopathy with statin use is a
significant clinical side effect. Recent guidelines recommend increasing
inclusion criteria for statin treatment in diabetic individuals; however, the
impact of statins on skeletal muscle health in those with diabetes (who already
suffer from impairments in muscle health) is ill defined. Here, we investigate
the effects of fluvastatin treatment on muscle health in wild type (WT) and
streptozotocin (STZ)-induced diabetic mice. WT and STZ-diabetic mice received
diet enriched with 600 mg/kg fluvastatin or control chow for 24 days. Muscle
morphology, intra and extracellular lipid levels, and lipid transporter content
were investigated. Our findings indicate that short-term fluvastatin
administration induced a myopathy that was not exacerbated by the presence of STZ
induced diabetes. Fluvastatin significantly increased ectopic lipid deposition
within the muscle of STZ-diabetic animals, findings that were not seen with
diabetes or statin treatment alone. Consistent with this observation, only
fluvastatin-treated diabetic mice downregulated protein expression of lipid
transporters FAT/CD36 and FABPpm in their skeletal muscle. No differences in
FAT/CD36 or FABPpm mRNA content were observed. Altered lipid compartmentalization
resultant of a downregulation in lipid transporter content in STZ-induced
diabetic skeletal muscle was apparent in the current investigation. Given the
association between ectopic lipid deposition in skeletal muscle and the
development of insulin-resistance, our findings highlight the necessity for more
thorough investigations into the impact of statins in humans with diabetes.
PMID- 27486435
TI - Dual Topology of the Melanocortin-2 Receptor Accessory Protein Is Stable.
AB - Melanocortin 2 receptor accessory protein (MRAP) facilitates trafficking of
melanocortin 2 (MC2) receptors and is essential for ACTH binding and signaling.
MRAP is a single transmembrane domain protein that forms antiparallel homodimers.
These studies ask when MRAP first acquires this dual topology, whether MRAP
architecture is static or stable, and whether the accessory protein undergoes
rapid turnover. To answer these questions, we developed an approach that
capitalizes on the specificity of bacterial biotin ligase, which adds biotin to
lysine in a short acceptor peptide sequence; the distinct mobility of MRAP
protomers of opposite orientations based on their N-linked glycosylation; and the
ease of identifying biotin-labeled proteins. We inserted biotin ligase acceptor
peptides at the N- or C-terminal ends of MRAP and expressed the modified proteins
in mammalian cells together with either cytoplasmic or endoplasmic reticulum
targeted biotin ligase. MRAP assumed dual topology early in biosynthesis in both
CHO and OS3 adrenal cells. Once established, MRAP orientation was stable. Despite
its conformational stability, MRAP displayed a half-life of under 2 h in CHO
cells. The amount of MRAP was increased by the proteasome inhibitor MG132 and
MRAP underwent ubiquitylation on lysine and other amino acids. Nonetheless, when
protein synthesis was blocked with cycloheximide, MRAP was rapidly degraded even
when MG132 was included and all lysines were replaced by arginines, implicating
non-proteasomal degradation pathways. The results show that although MRAP does
not change orientations during trafficking, its synthesis and degradation are
dynamically regulated.
PMID- 27486436
TI - Microbial Community Responses to Increased Water and Organic Matter in the Arid
Soils of the McMurdo Dry Valleys, Antarctica.
AB - The soils of the McMurdo Dry Valleys, Antarctica are an extreme polar desert,
inhabited exclusively by microscopic taxa. This region is on the threshold of
anticipated climate change, with glacial melt, permafrost thaw, and the melting
of massive buried ice increasing liquid water availability and mobilizing soil
nutrients. Experimental water and organic matter (OM) amendments were applied to
investigate how these climate change effects may impact the soil communities. To
identify active taxa and their functions, total community RNA transcripts were
sequenced and annotated, and amended soils were compared with unamended control
soils using differential abundance and expression analyses. Overall, taxonomic
diversity declined with amendments of water and OM. The domain Bacteria increased
with both amendments while Eukaryota declined from 38% of all taxa in control
soils to 8 and 11% in water and OM amended soils, respectively. Among bacterial
phyla, Actinobacteria (59%) dominated water-amended soils and Firmicutes (45%)
dominated OM amended soils. Three bacterial phyla (Actinobacteria,
Proteobacteria, and Firmicutes) were primarily responsible for the observed
positive functional responses, while eukaryotic taxa experienced the majority (27
of 34) of significant transcript losses. These results indicated that as climate
changes in this region, a replacement of endemic taxa adapted to dry,
oligotrophic conditions by generalist, copiotrophic taxa is likely.
PMID- 27486437
TI - Devices for In situ Development of Non-disturbed Oral Biofilm. A Systematic
Review.
AB - OBJECTIVE: The aim of this review was to assess the types of devices used for in
situ development of oral biofilm analyzed microbiologically. MATERIALS AND
METHODS: A systematic search of the literature was conducted to identify all in
situ studies of oral biofilm which used an oral device; the Ovid MEDLINE and
EMBASE databases complemented with manual search were used. Specific devices used
to microbiologically analyze oral biofilm in adults were included. After reading
of the selected full texts, devices were identified and classified according to
the oral cavity zone and manufacturing material. The "ideal" characteristics were
analyzed in every group. RESULTS: The search provided 787 abstracts, of which 111
papers were included. The devices used in these studies were classified as
palatal, lingual or buccal. The last group was sub-classified in six groups based
on the material of the device. Considering the analyzed characteristics, the
thermoplastic devices and the Intraoral Device of Overlaid Disk-holding Splints
(IDODS) presented more advantages than limitations. CONCLUSIONS: Buccal devices
were the most commonly used for the study of in situ biofilm. The majority of
buccal devices seemed to slightly affect the volunteer's comfort, the IDODS being
the closest to the "ideal" model. CLINICAL RELEVANCE: New devices for in situ
oral biofilm microbiological studies should take into account the possible effect
of their design on the volunteer's comfort and biofilm formation.
PMID- 27486438
TI - Metatranscriptional Response of Chemoautotrophic Ifremeria nautilei Endosymbionts
to Differing Sulfur Regimes.
AB - Endosymbioses between animals and chemoautotrophic bacteria are ubiquitous at
hydrothermal vents. These environments are distinguished by high physico-chemical
variability, yet we know little about how these symbioses respond to
environmental fluctuations. We therefore examined how the gamma-proteobacterial
symbionts of the vent snail Ifremeria nautilei respond to changes in sulfur
geochemistry. Via shipboard high-pressure incubations, we subjected snails to 105
MUM hydrogen sulfide (LS), 350 MUM hydrogen sulfide (HS), 300 MUM thiosulfate
(TS) and seawater without any added inorganic electron donor (ND). While
transcript levels of sulfur oxidation genes were largely consistent across
treatments, HS and TS treatments stimulated genes for denitrification, nitrogen
assimilation, and CO2 fixation, coincident with previously reported enhanced
rates of inorganic carbon incorporation and sulfur oxidation in these treatments.
Transcripts for genes mediating oxidative damage were enriched in the ND and LS
treatments, potentially due to a reduction in O2 scavenging when electron donors
were scarce. Oxidative TCA cycle gene transcripts were also more abundant in ND
and LS treatments, suggesting that I. nautilei symbionts may be mixotrophic when
inorganic electron donors are limiting. These data reveal the extent to which I.
nautilei symbionts respond to changes in sulfur concentration and species, and,
interpreted alongside coupled biochemical metabolic rates, identify gene targets
whose expression patterns may be predictive of holobiont physiology in
environmental samples.
PMID- 27486439
TI - Hantavirus Infection Suppresses Thrombospondin-1 Expression in Cultured
Endothelial Cells in a Strain-Specific Manner.
AB - Hantavirus infection is associated with two frequently fatal diseases in humans:
Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome
(HPS). The pathogenesis of hantavirus infection is complex and not fully
understood; however, it is believed to involve virus-induced hyperinflammatory
immune responses. Thrombospondin-1 (THBS1) is a large homotrimeric protein that
plays a putative role in regulating blood homeostasis. Hyperresponsiveness to
inflammatory stimuli has also been associated with defects in the THBS1 gene. Our
data suggest that hantavirus infection of human umbilical cord vein endothelial
cells (HUVEC) suppress the accumulation of THBS1 in the extracellular matrix.
Additionally, this suppression is dependent on virus replication, implying a
direct mechanism of action. Our data also imply that the pathogenic Andes and
Hantaan strains inhibit THBS1 expression while the non-pathogenic Prospect Hill
strain showed little inhibition. These observations suggest that a dysregulation
of THBS1 may contribute to the pathogenesis of hantavirus infection.
PMID- 27486440
TI - Genome and Transcriptome Sequences Reveal the Specific Parasitism of the
Nematophagous Purpureocillium lilacinum 36-1.
AB - Purpureocillium lilacinum is a promising nematophagous ascomycete able to adapt
diverse environments and it is also an opportunistic fungus that infects humans.
A microbial inoculant of P. lilacinum has been registered to control plant
parasitic nematodes. However, the molecular mechanism of the toxicological
processes is still unclear because of the relatively few reports on the subject.
In this study, using Illumina paired-end sequencing, the draft genome sequence
and the transcriptome of P. lilacinum strain 36-1 infecting nematode-eggs were
determined. Whole genome alignment indicated that P. lilacinum 36-1 possessed a
more dynamic genome in comparison with P. lilacinum India strain. Moreover, a
phylogenetic analysis showed that the P. lilacinum 36-1 had a closer relation to
entomophagous fungi. The protein-coding genes in P. lilacinum 36-1 occurred much
more frequently than they did in other fungi, which was a result of the depletion
of repeat-induced point mutations (RIP). Comparative genome and transcriptome
analyses revealed the genes that were involved in pathogenicity, particularly in
the recognition, adhesion of nematode-eggs, downstream signal transduction
pathways and hydrolase genes. By contrast, certain numbers of cellulose and xylan
degradation genes and a lack of polysaccharide lyase genes showed the potential
of P. lilacinum 36-1 as an endophyte. Notably, the expression of appressorium
formation and antioxidants-related genes exhibited similar infection patterns in
P. lilacinum strain 36-1 to those of the model entomophagous fungi Metarhizium
spp. These results uncovered the specific parasitism of P. lilacinum and
presented the genes responsible for the infection of nematode-eggs.
PMID- 27486441
TI - Analysis of Plant Growth-Promoting Effects of Fluorescent Pseudomonas Strains
Isolated from Mentha piperita Rhizosphere and Effects of Their Volatile Organic
Compounds on Essential Oil Composition.
AB - Many species or strains of the genus Pseudomonas have been characterized as plant
growth promoting rhizobacteria (PGPR). We used a combination of phenotypic and
genotypic techniques to analyze the community of fluorescent Pseudomonas strains
in the rhizosphere of commercially grown Mentha piperita (peppermint).
Biochemical techniques, Amplified rDNA Restriction Analysis (ARDRA), and 16S rRNA
gene sequence analysis revealed that the majority of the isolated native
fluorescent strains were P. putida. Use of two Repetitive Sequence-based PCR (rep
PCR) techniques, BOX-PCR and ERIC-PCR, allowed us to evaluate diversity among the
native strains and to more effectively distinguish among them. PGPR activity was
tested for the native strains and reference strain P. fluorescens WCS417r.
Micropropagated M. piperita plantlets were exposed to microbial volatile organic
compounds (mVOCs) emitted by the bacterial strains, and plant biomass parameters
and production of essential oils (EOs) were measured. mVOCs from 11 of the native
strains caused an increase in shoot fresh weight. mVOCs from three native strains
(SJ04, SJ25, SJ48) induced changes in M. pierita EO composition. The mVOCs caused
a reduction of metabolites in the monoterpene pathway, for example menthofuran,
and an increase in menthol production. Menthol production is the primary
indicator of EO quality. The mVOCs produced by native strains SJ04, SJ25, SJ48,
and strain WCS417r were analyzed. The obtained mVOC chromatographic profiles were
unique for each of the three native strains analyzed, containing varying
hydrocarbon, aromatic, and alogenic compounds. The differential effects of the
strains were most likely due to the specific mixtures of mVOCs emitted by each
strain, suggesting a synergistic effect occurs among the compounds present.
PMID- 27486442
TI - The Interaction between Arbuscular Mycorrhizal Fungi and Endophytic Bacteria
Enhances Plant Growth of Acacia gerrardii under Salt Stress.
AB - Microbes living symbiotically in plant tissues mutually cooperate with each other
by providing nutrients for proliferation of the partner organism and have a
beneficial effect on plant growth. However, few studies thus far have examined
the interactive effect of endophytic bacteria and arbuscular mycorrhizal fungi
(AMF) in hostile conditions and their potential to improve plant stress
tolerance. In this study, we investigated how the synergistic interactions of
endophytic bacteria and AMF affect plant growth, nodulation, nutrient acquisition
and stress tolerance of Acacia gerrardii under salt stress. Plant growth varied
between the treatments with both single inoculants and was higher in plants
inoculated with the endophytic B. subtilis strain than with AMF. Co-inoculated A.
gerrardii had a significantly greater shoot and root dry weight, nodule number,
and leghemoglobin content than those inoculated with AMF or B. subtilis alone
under salt stress. The endophytic B. subtilis could alleviate the adverse effect
of salt on AMF colonization. The differences in nitrate and nitrite reductase and
nitrogenase activities between uninoculated plants and those inoculated with AMF
and B. subtilis together under stress were significant. Both inoculation
treatments, either B. subtilis alone or combined with AMF, enhanced the N, P, K,
Mg, and Ca contents and phosphatase activities in salt-stressed A. gerrardii
tissues and reduced Na and Cl concentration, thereby protecting salt-stressed
plants from ionic and osmotic stress-induced changes. In conclusion, our results
indicate that endophytic bacteria and AMF contribute to a tripartite mutualistic
symbiosis in A. gerrardii and are coordinately involved in the plant adaptation
to salt stress tolerance.
PMID- 27486443
TI - Recovery of Heat Treated Bacillus cereus Spores Is Affected by Matrix Composition
and Factors with Putative Functions in Damage Repair.
AB - The ability of spores to recover and grow out after food processing is affected
by cellular factors and by the outgrowth conditions. In the current communication
we studied the recovery and outgrowth of individually sorted spores in BHI and
rice broth media and on agar plates using flow cytometry. We show that recovery
of wet heat treated Bacillus cereus ATCC 14579 spores is affected by matrix
composition with highest recovery in BHI broth or on rice agar plates, compared
to BHI agar plates and rice broth. Data show that not only media composition but
also its liquid or solid state affect the recovery of heat treated spores. To
determine the impact of factors with putative roles in recovery of heat treated
spores, specific genes previously shown to be highly expressed in outgrowing heat
treated spores were selected for mutant construction. Spores of nine B. cereus
ATCC 14579 deletion mutants were obtained and their recovery from wet heat
treatment was evaluated using BHI and rice broth and agar plates. Deletion mutant
spores showed different capacity to recover from heat treatment compared to wild
type with the most pronounced effect for a mutant lacking BC5242, a gene encoding
a membrane protein with C2C2 zinc finger which resulted in over 95% reduction in
recovery compared to the wild type in BHI broth. Notably, similar relative
performance of wild type and mutants was observed using the other recovery
conditions. We obtained insights on the impact of matrix composition and state on
recovery of individually sorted heat treated spores and identified cellular
factors with putative roles in this process. These results may provide leads for
future developments in design of more efficient combined preservation treatments.
PMID- 27486444
TI - The Resilience of Microbial Community under Drying and Rewetting Cycles of Three
Forest Soils.
AB - Forest soil ecosystems are associated with large pools and fluxes of carbon (C)
and nitrogen (N), which could be strongly affected by variation in rainfall
events under current climate change. Understanding how dry and wet cycle events
might influence the metabolic state of indigenous soil microbes is crucial for
predicting forest soil responses to environmental change. We used 454
pyrosequencing and quantitative PCR to address how present (DNA-based) and
potentially active (RNA-based) soil bacterial communities might response to the
changes in water availability across three different forest types located in two
continents (Africa and Asia) under controlled drying and rewetting cycles.
Sequencing of rRNA gene and transcript indicated that Proteobacteria,
Actinobacteria, and Acidobacteria were the most responsive phyla to changes in
water availability. We defined the ratio of rRNA transcript to rRNA gene
abundance as a key indicator of potential microbial activity and we found that
this ratio was increased following soil dry-down process whereas it decreased
after soil rewetting. Following rewetting Crenarchaeota-like 16S rRNA gene
transcript increased in some forest soils and this was linked to increases in
soil nitrate levels suggesting greater nitrification rates under higher soil
water availability. Changes in the relative abundance of (1) different microbial
phyla and classes, and (2) 16S and amoA genes were found to be site- and taxa
specific and might have been driven by different life-strategies. Overall, we
found that, after rewetting, the structure of the present and potentially active
bacterial community structure as well as the abundance of bacterial (16S),
archaeal (16S) and ammonia oxidizers (amoA), all returned to pre-dry-down levels.
This suggests that microbial taxa have the ability to recover from desiccation, a
critical response, which will contribute to maintaining microbial biodiversity in
harsh ecosystems under environmental perturbations, such as significant changes
in water availability.
PMID- 27486445
TI - Interaction of Bovine Peripheral Blood Polymorphonuclear Cells and Leptospira
Species; Innate Responses in the Natural Bovine Reservoir Host.
AB - Cattle are the reservoir hosts of Leptospira borgpetersenii serovar Hardjo, and
can also be reservoir hosts of other Leptospira species such as L. kirschneri,
and Leptospira interrogans. As a reservoir host, cattle shed Leptospira,
infecting other animals, including humans. Previous studies with human and murine
neutrophils have shown activation of neutrophil extracellular trap or NET
formation, and upregulation of inflammatory mediators by neutrophils in the
presence of Leptospira. Humans, companion animals and most widely studied models
of Leptospirosis are of acute infection, hallmarked by systemic inflammatory
response, neutrophilia, and septicemia. In contrast, cattle exhibit chronic
infection with few outward clinical signs aside from reproductive failure. Taking
into consideration that there is host species variation in innate immunity,
especially in pathogen recognition and response, the interaction of bovine
peripheral blood polymorphonuclear cells (PMNs) and several Leptospira strains
was evaluated. Studies including bovine-adapted strains, human pathogen strains,
a saprophyte and inactivated organisms. Incubation of PMNs with Leptospira did
induce slight activation of neutrophil NETs, greater than unstimulated cells but
less than the quantity from E. coli P4 stimulated PMNs. Very low but significant
from non-stimulated, levels of reactive oxygen peroxides were produced in the
presence of all Leptospira strains and E. coli P4. Similarly, significant levels
of reactive nitrogen intermediaries (NO2) was produced from PMNs when incubated
with the Leptospira strains and greater quantities in the presence of E. coli P4.
PMNs incubated with Leptospira induced RNA transcripts of IL-1beta, MIP-1alpha,
and TNF-alpha, with greater amounts induced by live organisms when compared to
heat-inactivated leptospires. Transcript for inflammatory cytokine IL-8 was also
induced, at similar levels regardless of Leptospira strain or viability. However,
incubation of Leptospira strains with bovine PMNs did not affect Leptospira
viability as measured by limiting dilution culture. This is in contrast to
previously reported results of innate inflammatory activation by Leptospira in
human and other animal models, or the activation and interaction of bovine PMNs
with Escherichia coli and other bacterial pathogens. While it could be
hypothesized that variations in innate receptor recognition, specifically
variance in toll-like receptor 2, could underlie the observed reduction of
activation in bovine PMNs, additional studies would be needed to explore this
possibility. Reduction in neutrophil responses may help to establish nearly
asymptomatic chronic Leptospira infection of cattle. This study emphasizes the
importance of studying host-pathogen relationships in the appropriate species as
extrapolation from other animal models may be incorrect and confounded by
differences in the host responses.
PMID- 27486447
TI - Thusin, a Novel Two-Component Lantibiotic with Potent Antimicrobial Activity
against Several Gram-Positive Pathogens.
AB - Due to the rapidly increasing prevalence of multidrug-resistant bacterial
strains, the need for new antimicrobial drugs to treat infections has become
urgent. Bacteriocins, which are antimicrobial peptides of bacterial origin, are
considered potential alternatives to conventional antibiotics and have attracted
widespread attention in recent years. Among these bacteriocins, lantibiotics,
especially two-component lantibiotics, exhibit potent antimicrobial activity
against some clinically relevant Gram-positive pathogens and have potential
applications in the pharmaceutical industry. In this study, we characterized a
novel two-component lantibiotic termed thusin that consists of Thsalpha, Thsbeta,
and Thsbeta' (mutation of Thsbeta, A14G) and that was isolated from a B.
thuringiensis strain BGSC 4BT1. Thsalpha and Thsbeta (or Thsbeta') exhibit
optimal antimicrobial activity at a 1:1 ratio and act sequentially to affect
target cells, and they are all highly thermostable (100 degrees C for 30 min) and
pH tolerant (pH 2.0 to 9.0). Thusin shows remarkable efficacy against all tested
Gram-positive bacteria and greater activities than two known lantibiotics
thuricin 4A-4 and ticin A4, and one antibiotic vancomycin against various
bacterial pathogens (Bacillus cereus, Listeria monocytogenes, Staphylococcus
aureus (MRSA), Staphylococcus sciuri, Enterococcus faecalis, and Streptococcus
pneumoniae). Moreover, thusin is also able to inhibit the outgrowth of B. cereus
spores. The potent antimicrobial activity of thusin against some Gram-positive
pathogens indicates that it has potential for the development of new drugs.
PMID- 27486446
TI - Insights into Bacteriophage Application in Controlling Vibrio Species.
AB - Bacterial infections from various organisms including Vibrio sp. pose a serious
hazard to humans in many forms from clinical infection to affecting the yield of
agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the
main foodborne pathogens causing human infection and is also a common cause of
losses in the aquaculture industry. Prophylactic and therapeutic usage of
antibiotics has become the mainstay of managing this problem, however, this in
turn led to the emergence of multidrug resistant strains of bacteria in the
environment; which has raised awareness of the critical need for alternative non
antibiotic based methods of preventing and treating bacterial infections.
Bacteriophages - viruses that infect and result in the death of bacteria - are
currently of great interest as a highly viable alternative to antibiotics. This
article provides an insight into bacteriophage application in controlling Vibrio
species as well underlining the advantages and drawbacks of phage therapy.
PMID- 27486448
TI - Transfer of a Catabolic Pathway for Chloromethane in Methylobacterium Strains
Highlights Different Limitations for Growth with Chloromethane or with
Dichloromethane.
AB - Chloromethane (CM) is an ozone-depleting gas, produced predominantly from natural
sources, that provides an important carbon source for microbes capable of
consuming it. CM catabolism has been difficult to study owing to the challenging
genetics of its native microbial hosts. Since the pathways for CM catabolism show
evidence of horizontal gene transfer, we reproduced this transfer process in the
laboratory to generate new CM-catabolizing strains in tractable hosts. We
demonstrate that six putative accessory genes improve CM catabolism, though
heterologous expression of only one of the six is strictly necessary for growth
on CM. In contrast to growth of Methylobacterium strains with the closely related
compound dichloromethane (DCM), we find that chloride export does not limit
growth on CM and, in general that the ability of a strain to grow on DCM is
uncorrelated with its ability to grow on CM. This heterologous expression system
allows us to investigate the components required for effective CM catabolism and
the factors that limit effective catabolism after horizontal transfer.
PMID- 27486449
TI - Complete Sequence of pEC012, a Multidrug-Resistant IncI1 ST71 Plasmid Carrying
bla CTX-M-65, rmtB, fosA3, floR, and oqxAB in an Avian Escherichia coli ST117
Strain.
AB - A 139,622-bp IncI1 ST71 conjugative plasmid pEC012 from an avian Escherichia coli
D-ST117 strain was sequenced, which carried five IS26-bracketed resistance
modules: IS26-fosA3-orf1-orf2-Deltaorf3-IS26, IS26-fip-DeltaISEcp1-bla CTX-M-65
IS903D-iroN-IS26, IS26-DeltatnpR-bla TEM-1-rmtB-IS26, IS26-oqxAB-IS26, and IS26
floR-aac(3)-IV-IS26. The backbone of pEC012 was similar to that of several other
IncI1 ST71 plasmids: pV408, pM105, and pC271, but these plasmids had different
arrangements of multidrug resistance region. In addition, the novel ISEc57
element was identified, which is in the IS21 family. The stepwise emergence of
multi-resistance regions demonstrated the accumulation of different resistance
determinants through homologous recombination. To the best of our knowledge, this
is the first study to identify a multidrug-resistant IncI1 ST71 plasmid carrying
bla CTX-M-65, rmtB, fosA3, floR, and oqxAB in an avian E. coli ST117 strain.
PMID- 27486450
TI - The Lp_3561 and Lp_3562 Enzymes Support a Functional Divergence Process in the
Lipase/Esterase Toolkit from Lactobacillus plantarum.
AB - Lactobacillus plantarum species is a good source of esterases since both
lipolytic and esterase activities have been described for strains of this
species. No fundamental biochemical difference exists among esterases and lipases
since both share a common catalytic mechanism. L. plantarum WCFS1 possesses a
protein, Lp_3561, which is 44% identical to a previously described lipase,
Lp_3562. In contrast to Lp_3562, Lp_3561 was unable to degrade esters possessing
a chain length higher than C4 and the triglyceride tributyrin. As in other L.
plantarum esterases, the electrostatic potential surface around the active site
in Lp_3561 is predicted to be basic, whereas it is essentially neutral in the
Lp_3562 lipase. The fact that the genes encoding both proteins were located
contiguously in the L. plantarum WCFS1 genome, suggests that they originated by
tandem duplication, and therefore are paralogs as new functions have arisen
during evolution. The presence of the contiguous lp_3561 and lp_3562 genes was
studied among L. plantarum strains. They are located in a 8,903 bp DNA fragment
that encodes proteins involved in the catabolism of sialic acid and are predicted
to increase bacterial adaptability under certain growth conditions.
PMID- 27486451
TI - Characterization of a New Cold-Adapted and Salt-Activated Polysaccharide Lyase
Family 7 Alginate Lyase from Pseudoalteromonas sp. SM0524.
AB - Marine bacterial alginate lyases play a role in marine alginate degradation and
carbon cycling. Although a large number of alginate lyases have been
characterized, reports on alginate lyases with special characteristics are still
rather less. Here, a gene alyPM encoding an alginate lyase of polysaccharide
lyase family 7 (PL7) was cloned from marine Pseudoalteromonas sp. SM0524 and
expressed in Escherichia coli. AlyPM shows 41% sequence identity to characterized
alginate lyases, indicating that AlyPM is a new PL7 enzyme. The optimal pH for
AlyPM activity was 8.5. AlyPM showed the highest activity at 30 degrees C and
remained 19% of the highest activity at 5 degrees C. AlyPM was unstable at
temperatures above 30 degrees C and had a low T m of 37 degrees C. These data
indicate that AlyPM is a cold-adapted enzyme. Moreover, AlyPM is a salt-activated
enzyme. AlyPM activity in 0.5-1.2 M NaCl was sixfolds higher than that in 0 M
NaCl, probably caused by a significant increase in substrate affinity, because
the K m of AlyPM in 0.5 M NaCl decreased more than 20-folds than that in 0 M
NaCl. AlyPM preferably degraded polymannuronate and mainly released dimers and
trimers. These data indicate that AlyPM is a new PL7 endo-alginate lyase with
special characteristics.
PMID- 27486452
TI - Methane Inhibition Alters the Microbial Community, Hydrogen Flow, and
Fermentation Response in the Rumen of Cattle.
AB - Management of metabolic hydrogen ([H]) in the rumen has been identified as an
important consideration when reducing ruminant CH4 emissions. However, little is
known about hydrogen flux and microbial rumen population responses to CH4
inhibition when animals are fed with slowly degradable diets. The effects of the
anti-methanogenic compound, chloroform, on rumen fermentation, microbial ecology,
and H2/CH4 production were investigated in vivo. Eight rumen fistulated Brahman
steers were fed a roughage hay diet (Rhode grass hay) or roughage hay:concentrate
diet (60:40) with increasing levels (low, mid, and high) of chloroform in a
cyclodextrin matrix. The increasing levels of chloroform resulted in an increase
in H2 expelled as CH4 production decreased with no effect on dry matter intakes.
The amount of expelled H2 per mole of decreased methane, was lower for the hay
diet suggesting a more efficient redirection of hydrogen into other microbial
products compared with hay:concentrate diet. A shift in rumen fermentation toward
propionate and branched-chain fatty acids was observed for both diets. Animals
fed with the hay:concentrate diet had both higher formate concentration and H2
expelled than those fed only roughage hay. Metabolomic analyses revealed an
increase in the concentration of amino acids, organic, and nucleic acids in the
fluid phase for both diets when methanogenesis was inhibited. These changes in
the rumen metabolism were accompanied by a shift in the microbiota with an
increase in Bacteroidetes:Firmicutes ratio and a decrease in Archaea and
Synergistetes for both diets. Within the Bacteroidetes family, some OTUs assigned
to Prevotella were promoted under chloroform treatment. These bacteria may be
partly responsible for the increase in amino acids and propionate in the rumen.
No significant changes were observed for abundance of fibrolytic bacteria,
protozoa, and fungi, which suggests that fiber degradation was not impaired. The
observed 30% decrease in methanogenesis did not adversely affect rumen metabolism
and the rumen microbiota was able to adapt and redirect [H] into other microbial
end-products for both diets. However, it is also required dietary supplements or
microbial treatments to capture the additional H2 expelled by the animal to
further improve rumen digestive efficiency.
PMID- 27486453
TI - Stress Conditions Induced by Carvacrol and Cinnamaldehyde on Acinetobacter
baumannii.
AB - Acinetobacter baumannii has emerged as a major cause of nosocomial infections.
The ability of A. baumannii to display various resistance mechanisms against
antibiotics has transformed it into a successful nosocomial pathogen. The limited
number of antibiotics in development and the disengagement of the pharmaceutical
industry have prompted the development of innovative strategies. One of these
strategies is the use of essential oils, especially aromatic compounds that are
potent antibacterial molecules. Among them, the combination of carvacrol and
cinnamaldehyde has already demonstrated antibacterial efficacy against A.
baumannii. The aim of this study was to determine the biological effects of these
two compounds in A. baumannii, describing their effect on the rRNA and gene
regulation under environmental stress conditions. Results demonstrated rRNA
degradation by the carvacrol/cinnamaldehyde mixture, and this effect was due to
carvacrol. Degradation was conserved after encapsulation of the mixture in lipid
nanocapsules. Results showed an upregulation of the genes coding for heat shock
proteins, such as groES, groEL, dnaK, clpB, and the catalase katE, after exposure
to carvacrol/cinnamaldehyde mixture. The catalase was upregulated after carvacrol
exposure wich is related to an oxidative stress. The combination of thiourea
(hydroxyl radical scavenger) and carvacrol demonstrated a potent bactericidal
effect. These results underline the development of defense strategies of the
bacteria by synthesis of reactive oxygen species in response to environmental
stress conditions, such as carvacrol.
PMID- 27486454
TI - Probing Synechocystis-Arsenic Interactions through Extracellular Nanowires.
AB - Microbial nanowires (MNWs) can play an important role in the transformation and
mobility of toxic metals/metalloids in environment. The potential role of MNWs in
cell-arsenic (As) interactions has not been reported in microorganisms and thus
we explored this interaction using Synechocystis PCC 6803 as a model system. The
effect of half maximal inhibitory concentration (IC50) [~300 mM As (V) and ~4 mM
As (III)] and non-inhibitory [4X lower than IC50, i.e., 75 mM As (V) and 1 mM As
(III)] of As was studied on Synechocystis cells in relation to its effect on
Chlorophyll (Chl) a, type IV pili (TFP)-As interaction and
intracellular/extracellular presence of As. In silico analysis showed that
subunit PilA1 of electrically conductive TFP, i.e., microbial nanowires of
Synechocystis have putative binding sites for As. In agreement with in silico
analysis, transmission electron microscopy analysis showed that As was deposited
on Synechocystis nanowires at all tested concentrations. The potential of
Synechocystis nanowires to immobilize As can be further enhanced and evaluated on
a large scale and thus can be applied for bioremediation studies.
PMID- 27486455
TI - Exploring the Diversity and Antimicrobial Potential of Marine Actinobacteria from
the Comau Fjord in Northern Patagonia, Chile.
AB - Bioprospecting natural products in marine bacteria from fjord environments are
attractive due to their unique geographical features. Although, Actinobacteria
are well known for producing a myriad of bioactive compounds, investigations
regarding fjord-derived marine Actinobacteria are scarce. In this study, the
diversity and biotechnological potential of Actinobacteria isolated from marine
sediments within the Comau fjord, in Northern Chilean Patagonia, were assessed by
culture-based approaches. The 16S rRNA gene sequences revealed that members
phylogenetically related to the Micrococcaceae, Dermabacteraceae,
Brevibacteriaceae, Corynebacteriaceae, Microbacteriaceae, Dietziaceae,
Nocardiaceae, and Streptomycetaceae families were present at the Comau fjord. A
high diversity of cultivable Actinobacteria (10 genera) was retrieved by using
only five different isolation media. Four isolates belonging to Arthrobacter,
Brevibacterium, Corynebacterium and Kocuria genera showed 16S rRNA gene identity
<98.7% suggesting that they are novel species. Physiological features such as
salt tolerance, artificial sea water requirement, growth temperature,
pigmentation and antimicrobial activity were evaluated. Arthrobacter,
Brachybacterium, Curtobacterium, Rhodococcus, and Streptomyces isolates showed
strong inhibition against both Gram-negative Pseudomonas aeruginosa, Escherichia
coli and Salmonella enterica and Gram-positive Staphylococcus aureus, Listeria
monocytogenes. Antimicrobial activities in Brachybacterium, Curtobacterium, and
Rhodococcus have been scarcely reported, suggesting that non-mycelial strains are
a suitable source of bioactive compounds. In addition, all strains bear at least
one of the biosynthetic genes coding for NRPS (91%), PKS I (18%), and PKS II
(73%). Our results indicate that the Comau fjord is a promising source of novel
Actinobacteria with biotechnological potential for producing biologically active
compounds.
PMID- 27486456
TI - Factors Determining Staphylococcus aureus Susceptibility to Photoantimicrobial
Chemotherapy: RsbU Activity, Staphyloxanthin Level, and Membrane Fluidity.
AB - Photoantimicrobial chemotherapy (PACT) constitutes a particular type of stress
condition, in which bacterial cells induce a pleiotropic and as yet unexplored
effect. In light of this, the key master regulators are of putative significance
to the overall phototoxic outcome. In Staphylococcus aureus, the alternative
sigma factor sigma(B) controls the expression of genes involved in the response
to environmental stress. We show that aberration of any sigB operon genes in S.
aureus USA300 isogenic mutants causes a pronounced sensitization (>5 log10
reduction in CFU drop) to PACT with selected photosensitizers, namely
protoporphyrin diarginate, zinc phthalocyanine and rose bengal. This effect is
partly due to aberration-coupled staphyloxanthin synthesis inhibition. We
identified frequent mutations in RsbU, a sigma(B) activator, in PACT-vulnerable
clinical isolates of S. aureus, resulting in sigma(B) activity impairment.
Locations of significant changes in protein structure (IS256 insertion, early
STOP codon occurrence, substitutions A230T and A276D) were shown in a theoretical
model of S. aureus RsbU. As a phenotypic hallmark of PACT-vulnerable S. aureus
strains, we observed an increased fluidity of bacterial cell membrane, which is a
result of staphyloxanthin content and other yet unidentified factors. Our
research indicates sigma(B) as a promising target of adjunctive antimicrobial
therapy and suggests that enhanced cell membrane fluidity may be an adjuvant
strategy in PACT.
PMID- 27486457
TI - Three CoA Transferases Involved in the Production of Short Chain Fatty Acids in
Porphyromonas gingivalis.
AB - Butyryl-CoA:acetate CoA transferase, which produces butyrate and acetyl-CoA from
butyryl-CoA and acetate, is responsible for the final step of butyrate production
in bacteria. This study demonstrates that in the periodontopathogenic bacterium
Porphyromonas gingivalis this reaction is not catalyzed by PGN_1171, previously
annotated as butyryl-CoA:acetate CoA transferase, but by three distinct CoA
transferases, PGN_0725, PGN_1341, and PGN_1888. Gas chromatography/mass
spectrometry (GC-MS) and spectrophotometric analyses were performed using crude
enzyme extracts from deletion mutant strains and purified recombinant proteins.
The experiments revealed that, in the presence of acetate, PGN_0725
preferentially utilized butyryl-CoA rather than propionyl-CoA. By contrast, this
preference was reversed in PGN_1888. The only butyryl-CoA:acetate CoA transferase
activity was observed in PGN_1341. Double reciprocal plots revealed that all the
reactions catalyzed by these enzymes follow a ternary-complex mechanism, in
contrast to previously characterized CoA transferases. GC-MS analysis to
determine the concentrations of short chain fatty acids (SCFAs) in culture
supernatants of P. gingivalis wild type and mutant strains revealed that PGN_0725
and PGN_1888 play a major role in the production of butyrate and propionate,
respectively. Interestingly, a triple deletion mutant lacking PGN_0725, PGN_1341,
and PGN_1888 produced low levels of SCFAs, suggesting that the microorganism
contains CoA transferase(s) in addition to these three enzymes. Growth rates of
the mutant strains were mostly slower than that of the wild type, indicating that
many carbon compounds produced in the SCFA synthesis appear to be important for
the biological activity of this microorganism.
PMID- 27486458
TI - Antimicrobial Activity of Mast Cells: Role and Relevance of Extracellular DNA
Traps.
AB - Mast cells (MCs) have been shown to release their nuclear DNA and subsequently
form mast cell extracellular traps (MCETs) comparable to neutrophil extracellular
traps, which are able to entrap and kill various microbes. The formation of
extracellular traps is associated with the disruption of the nuclear membrane,
which leads to mixing of nuclear compounds with granule components and causes the
death of the cell, a process called ETosis. The question arises why do MCs
release MCETs although they are very well known as multifunctional long-living
sentinel cells? MCs are known to play a role during allergic reactions and
certain parasitic infections. Nonetheless, they are also critical components of
the early host innate immune response to bacterial and fungal pathogens: MCs
contribute to the initiation of the early immune response by recruiting effector
cells including neutrophils and macrophages by locally releasing inflammatory
mediators, such as TNF-alpha. Moreover, various studies demonstrate that MCs are
able to eliminate microbes through intracellular as well as extracellular
antimicrobial mechanisms, including MCET formation similar to that of
professional phagocytes. Recent literature leads to the suggestion that MCET
formation is not the result of a passive release of DNA and granule proteins
during cellular disintegration, but rather an active and controlled process in
response to specific stimulation, which contributes to the innate host defense.
This review will discuss the different known aspects of the antimicrobial
activities of MCs with a special focus on MCETs, and their role and relevance
during infection and inflammation.
PMID- 27486460
TI - M1- and M2-Type Macrophage Responses Are Predictive of Adverse Outcomes in Human
Atherosclerosis.
AB - Atherosclerosis is an inflammatory disease caused by endothelial injury, lipid
deposition, and oxidative stress. This progressive disease can be converted into
an acute clinical event by plaque rupture and thrombosis. In the context of
atherosclerosis, the underlying cause of myocardial infarction and stroke,
macrophages uniquely possess a dual functionality, regulating lipid accumulation
and metabolism and sustaining the chronic inflammatory response, two of the most
well-documented pathways associated with the pathogenesis of the disease.
Macrophages are heterogeneous cell populations and it is hypothesized that,
during the pathogenesis of atherosclerosis, macrophages in the developing plaque
can switch from a pro-inflammatory (MPhi1) to an anti-inflammatory (MPhi2)
phenotype and vice versa, depending on the microenvironment. The aim of this
study was to identify changes in macrophage subpopulations in the progression of
human atherosclerotic disease. Established atherosclerotic plaques from
symptomatic and asymptomatic patients with existing coronary artery disease
undergoing carotid endarterectomy were recruited to the study. Comprehensive
histological and immunohistochemical analyses were performed to quantify the
cellular content and macrophage subsets of atherosclerotic lesion. In parallel,
expression of MPhi1 and MPhi2 macrophage markers were analyzed by real-time PCR
and Western blot analysis. Gross analysis and histological staining demonstrated
that symptomatic plaques presented greater hemorrhagic activity and the internal
carotid was the most diseased segment, based on the predominant prevalence of
fibrotic and necrotic tissue, calcifications, and hemorrhagic events.
Immunohistochemical analysis showed that both MPhi1 and MPhi2 macrophages are
present in human plaques. However, MPhi2 macrophages are localized to more stable
locations within the lesion. Importantly, gene and protein expression analysis of
MPhi1/MPhi2 markers evidenced that MPhi1 markers and Th1-associated cytokines are
highly expressed in symptomatic plaques, whereas expression of the MPhi2 markers,
mannose receptor (MR), and CD163 and Th2 cytokines are inversely related with
disease progression. These data increase the understanding of atherosclerosis
development, identifying the cellular content of lesions during disease
progression, and characterizing macrophage subpopulation within human
atherosclerotic plaques.
PMID- 27486459
TI - Transcriptome Analysis of B Cell Immune Functions in Periodontitis: Mucosal
Tissue Responses to the Oral Microbiome in Aging.
AB - Evidence has shown activation of T and B cells in gingival tissues in
experimental models and in humans diagnosed with periodontitis. The results of
this adaptive immune response are noted both locally and systemically with
antigenic specificity for an array of oral bacteria, including periodontopathic
species, e.g., Porphyromonas gingivalis and Aggregatibacter
actinomycetemcomitans. It has been recognized through epidemiological studies and
clinical observations that the prevalence of periodontitis increases with age.
This report describes our studies evaluating gingival tissue transcriptomes in
humans and specifically exploiting the use of a non-human primate model of
naturally occurring periodontitis to delineate gingival mucosal tissue gene
expression profiles focusing on cells/genes critical for the development of
humoral adaptive immune responses. Patterns of B cell and plasmacyte genes were
altered in aging healthy gingival tissues. Substantial increases in a large
number of genes reflecting antigen-dependent activation, B cell activation, B
cell proliferation, and B cell differentiation/maturation were observed in
periodontitis in adults and aged animals. Finally, evaluation of the relationship
of these gene expression patterns with those of various tissue destructive
molecules (MMP2, MMP9, CTSK, TNFalpha, and RANKL) showed a greater frequency of
positive correlations in healthy tissues versus periodontitis tissues, with only
MMP9 correlations similar between the two tissue types. These results are
consistent with B cell response activities in healthy tissues potentially
contributing to muting the effects of the tissue destructive biomolecules,
whereas with periodontitis this relationship is adversely affected and enabling a
progression of tissue destructive events.
PMID- 27486461
TI - Transforming Growth Factor-beta-Activated Kinase 1 Is Required for Human
FcgammaRIIIb-Induced Neutrophil Extracellular Trap Formation.
AB - Neutrophils (PMNs) are the most abundant leukocytes in the blood. PMN migrates
from the circulation to sites of infection where they are responsible for
antimicrobial functions. PMN uses phagocytosis, degranulation, and formation of
neutrophil extracellular traps (NETs) to kill microbes. Several stimuli,
including bacteria, fungi, and parasites, and some pharmacological compounds,
such as Phorbol 12-myristate 13-acetate (PMA), are efficient inducers of NETs.
Antigen-antibody complexes are also capable of inducing NET formation. Recently,
it was reported that FcgammaRIIIb cross-linking induced NET formation similarly
to PMA stimulation. Direct cross-linking of FcgammaRIIA or integrins did not
promote NET formation. FcgammaRIIIb-induced NET formation presented different
kinetics from PMA-induced NET formation, suggesting differences in signaling.
Because FcgammaRIIIb also induces a strong activation of extracellular signal
regulated kinase (ERK) and nuclear factor Elk-1, and the transforming growth
factor-beta-activated kinase 1 (TAK1) has recently been implicated in ERK
signaling, in the present report, we explored the role of TAK1 in the signaling
pathway activated by FcgammaRIIIb leading to NET formation. FcgammaRIIIb was
stimulated by specific monoclonal antibodies, and NET formation was evaluated in
the presence or absence of pharmacological inhibitors. The antibiotic LL Z1640-2,
a selective inhibitor of TAK1 prevented FcgammaRIIIb-induced, but not PMA-induced
NET formation. Both PMA and FcgammaRIIIb cross-linking induced phosphorylation of
ERK. But, LL Z1640-2 only inhibited the FcgammaRIIIb-mediated activation of ERK.
Also, only FcgammaRIIIb, similarly to transforming growth factor-beta-induced
TAK1 phosphorylation. A MEK (ERK kinase)-specific inhibitor was able to prevent
ERK phosphorylation induced by both PMA and FcgammaRIIIb. These data show for the
first time that FcgammaRIIIb cross-linking activates TAK1, and that this kinase
is required for triggering the MEK/ERK signaling pathway to NETosis.
PMID- 27486462
TI - Remodeling of Leaf Cellular Glycerolipid Composition under Drought and Re
hydration Conditions in Grasses from the Lolium-Festuca Complex.
AB - Drought tolerant plant genotypes are able to maintain stability and integrity of
cellular membranes in unfavorable conditions, and to regenerate damaged membranes
after stress cessation. The profiling of cellular glycerolipids during drought
stress performed on model species such as Arabidopsis thaliana does not fully
cover the picture of lipidome in monocots, including grasses. Herein, two closely
related introgression genotypes of Lolium multiflorum (Italian ryegrass) *
Festuca arundinacea (tall fescue) were used as a model for other grass species to
describe lipid rearrangements during drought and re-hydration. The genotypes
differed in their level of photosynthetic capacity during drought, and in their
capacity for membrane regeneration after stress cessation. A total of 120 lipids,
comprising the classes of monogalactosyldiacyloglycerol,
digalactosyldiacyloglycerol, sulfoquinovosyldiacylglycerol, phosphatidylglycerol,
phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine,
phosphatidylinositol, diacylglicerol, and triacylglicerol, were analyzed. The
results clearly showed that water deficit had a significant impact on lipid
metabolism in studied forage grasses. It was revealed that structural and
metabolic lipid species changed their abundance during drought and re-watering
periods and some crucial genotype-dependent differences were also observed. The
introgression genotype characterized by an ability to regenerate membranes after
re-hydration demonstrated a higher accumulation level of most chloroplast and
numerous extra-chloroplast membrane lipid species at the beginning of drought.
Furthermore, this genotype also revealed a significant reduction in the
accumulation of most chloroplast lipids after re-hydration, compared with the
other introgression genotype without the capacity for membrane regeneration. The
potential influence of observed lipidomic alterations on a cellular membrane
stability and photosynthetic capacity, are discussed. HIGHLIGHTS A higher drought
tolerance of grasses could be associated with an earlier lipidome response to a
stress signal and with a membrane regeneration after stress cessation accompanied
by a turnover of chloroplast lipids.
PMID- 27486463
TI - New Insights on Eggplant/Tomato/Pepper Synteny and Identification of Eggplant and
Pepper Orthologous QTL.
AB - Eggplant, pepper, and tomato are the most exploited berry-producing vegetables
within the Solanaceae family. Their genomes differ in size, but each has 12
chromosomes which have undergone rearrangements causing a redistribution of loci.
The genome sequences of all three species are available but differ in coverage,
assembly quality and percentage of anchorage. Determining their syntenic
relationship and QTL orthology will contribute to exploit genomic resources and
genetic data for key agronomic traits. The syntenic analysis between tomato and
pepper based on the alignment of 34,727 tomato CDS to the pepper genome sequence,
identified 19,734 unique hits. The resulting synteny map confirmed the 14
inversions and 10 translocations previously documented, but also highlighted 3
new translocations and 4 major new inversions. Furthermore, each of the 12
chromosomes exhibited a number of rearrangements involving small regions of 0.5
0.7 Mbp. Due to high fragmentation of the publicly available eggplant genome
sequence, physical localization of most eggplant QTL was not possible, thus, we
compared the organization of the eggplant genetic map with the genome sequence of
both tomato and pepper. The eggplant/tomato syntenic map confirmed all the 10
translocations but only 9 of the 14 known inversions; on the other hand, a newly
detected inversion was recognized while another one was not confirmed. The
eggplant/pepper syntenic map confirmed 10 translocations and 8 inversions already
detected and suggested a putative new translocation. In order to perform the
assessment of eggplant and pepper QTL orthology, the eggplant and pepper sequence
based markers located in their respective genetic map were aligned onto the
pepper genome. GBrowse in pepper was used as reference platform for QTL
positioning. A set of 151 pepper QTL were located as well as 212 eggplant QTL,
including 76 major QTL (PVE >= 10%) affecting key agronomic traits. Most were
confirmed to cluster in orthologous chromosomal regions. Our results highlight
that the availability of genome sequences for an increasing number of crop
species and the development of "ultra-dense" physical maps provide new and key
tools for detailed syntenic and orthology studies between related plant species.
PMID- 27486464
TI - Genome-Wide QTL Mapping for Wheat Processing Quality Parameters in a Gaocheng
8901/Zhoumai 16 Recombinant Inbred Line Population.
AB - Dough rheological and starch pasting properties play an important role in
determining processing quality in bread wheat (Triticum aestivum L.). In the
present study, a recombinant inbred line (RIL) population derived from a Gaocheng
8901/Zhoumai 16 cross grown in three environments was used to identify
quantitative trait loci (QTLs) for dough rheological and starch pasting
properties evaluated by Mixograph, Rapid Visco-Analyzer (RVA), and Mixolab
parameters using the wheat 90 and 660 K single nucleotide polymorphism (SNP) chip
assays. A high-density linkage map constructed with 46,961 polymorphic SNP
markers from the wheat 90 and 660 K SNP assays spanned a total length of 4121 cM,
with an average chromosome length of 196.2 cM and marker density of 0.09
cM/marker; 6596 new SNP markers were anchored to the bread wheat linkage map,
with 1046 and 5550 markers from the 90 and 660 K SNP assays, respectively.
Composite interval mapping identified 119 additive QTLs on 20 chromosomes except
4D; among them, 15 accounted for more than 10% of the phenotypic variation across
two or three environments. Twelve QTLs for Mixograph parameters, 17 for RVA
parameters and 55 for Mixolab parameters were new. Eleven QTL clusters were
identified. The closely linked SNP markers can be used in marker-assisted wheat
breeding in combination with the Kompetitive Allele Specific PCR (KASP) technique
for improvement of processing quality in bread wheat.
PMID- 27486465
TI - Plant Recycling for Molecular Biofarming to Produce Recombinant Anti-Cancer mAb.
AB - The expression and glycosylation patterns of anti-colorectal cancer therapeutic
monoclonal antibody (mAb) CO17-1A recognizing the tumor-associated antigen GA733
2, expressed in human colorectal carcinoma cells, were observed in the leaf and
stem tissues of primary (0 cycle), secondary (1 cycle), and tertiary (2 cycle)
growths of seedlings obtained from the stem cut of T2 plants. The bottom portion
of the stem of T2 seedlings was cut to induce the 1 cycle shoot growth, which was
again cut to induce the 2 cycle shoot growth. In the 1 and 2 cycle growths, the
periods for floral organ formation (35 days) was shorter than that (100 days) for
the 0 cycle growth. The genes of heavy and light chains of mAb CO17-1A existed at
the top, middle, and basal portions of the leaves and stem obtained from the 0,
1, and 2 cycle plants. The protein levels in the leaves and stem tissues from the
1 and 2 cycles were similar to those in the tissues from the 0 cycle. The
glycosylation level and pattern in the leaf and stem did not alter dramatically
over the different cycles. Surface plasmon resonance (SPR) confirmed that mAbs
CO17-1A obtained from leaf and stem tissues of the 0, 1, and 2 cycles had similar
binding affinity for the GA733-2 antigen. These data suggest that the shoot
growth by bottom stem cutting is applicable to speed up the growth of plant
biomass expressing anti-colorectal cancer mAb without variation of expression,
glycosylation, and functionality.
PMID- 27486466
TI - Identification and Comparative Analysis of Differential Gene Expression in
Soybean Leaf Tissue under Drought and Flooding Stress Revealed by RNA-Seq.
AB - Drought and flooding are two major causes of severe yield loss in soybean
worldwide. A lack of knowledge of the molecular mechanisms involved in drought
and flood stress has been a limiting factor for the effective management of
soybeans; therefore, it is imperative to assess the expression of genes involved
in response to flood and drought stress. In this study, differentially expressed
genes (DEGs) under drought and flooding conditions were investigated using
Illumina RNA-Seq transcriptome profiling. A total of 2724 and 3498 DEGs were
identified under drought and flooding treatments, respectively. These genes
comprise 289 Transcription Factors (TFs) representing Basic Helix-loop Helix
(bHLH), Ethylene Response Factors (ERFs), myeloblastosis (MYB), No apical
meristem (NAC), and WRKY amino acid motif (WRKY) type major families known to be
involved in the mechanism of stress tolerance. The expression of photosynthesis
and chlorophyll synthesis related genes were significantly reduced under both
types of stresses, which limit the metabolic processes and thus help prolong
survival under extreme conditions. However, cell wall synthesis related genes
were up-regulated under drought stress and down-regulated under flooding stress.
Transcript profiles involved in the starch and sugar metabolism pathways were
also affected under both stress conditions. The changes in expression of genes
involved in regulating the flux of cell wall precursors and starch/sugar content
can serve as an adaptive mechanism for soybean survival under stress conditions.
This study has revealed the involvement of TFs, transporters, and photosynthetic
genes, and has also given a glimpse of hormonal cross talk under the extreme
water regimes, which will aid as an important resource for soybean crop
improvement.
PMID- 27486467
TI - Application of the Ribosomal DNA ITS2 Region of Physalis (Solanaceae): DNA
Barcoding and Phylogenetic Study.
AB - Recently, commercial interest in Physalis species has grown worldwide due to
their high nutritional value, edible fruit, and potential medicinal properties.
However, many Physalis species have similar shapes and are easily confused, and
consequently the phylogenetic relationships between Physalis species are poorly
understood. This hinders their safe utilization and genetic resource
conservation. In this study, the nuclear ribosomal ITS2 region was used to
identify species and phylogenetically examine Physalis. Eighty-six ITS2 regions
from 45 Physalis species were analyzed. The ITS2 sequences were aligned using
Clustal W and genetic distances were calculated using MEGA V6.0. The results
showed that ITS2 regions have significant intra- and inter-specific divergences,
obvious barcoding gaps, and higher species discrimination rates (82.2% for both
the BLASTA1 and nearest distance methods). In addition, the secondary structure
of ITS2 provided another way to differentiate species. Cluster analysis based on
ITS2 regions largely concurred with the relationships among Physalis species
established by many previous molecular analyses, and showed that most sections of
Physalis appear to be polyphyletic. Our results demonstrated that ITS2 can be
used as an efficient and powerful marker in the identification and phylogenetic
study of Physalis species. The technique provides a scientific basis for the
conservation of Physalis plants and for utilization of resources.
PMID- 27486468
TI - Leaf Treatments with a Protein-Based Resistance Inducer Partially Modify
Phyllosphere Microbial Communities of Grapevine.
AB - Protein derivatives and carbohydrates can stimulate plant growth, increase stress
tolerance, and activate plant defense mechanisms. However, these molecules can
also act as a nutritional substrate for microbial communities living on the plant
phyllosphere and possibly affect their biocontrol activity against pathogens. We
investigated the mechanisms of action of a protein derivative (nutrient broth,
NB) against grapevine downy mildew, specifically focusing on the effects of
foliar treatments on plant defense stimulation and on the composition and
biocontrol features of the phyllosphere microbial populations. NB reduced downy
mildew symptoms and induced the expression of defense-related genes in greenhouse
and in vitro-grown plants, indicating the activation of grapevine resistance
mechanisms. Furthermore, NB increased the number of culturable phyllosphere
bacteria and altered the composition of bacterial and fungal populations on
leaves of greenhouse-grown plants. Although, NB-induced changes on microbial
populations were affected by the structure of indigenous communities originally
residing on grapevine leaves, degrees of disease reduction and defense gene
modulation were consistent among the experiments. Thus, modifications in the
structure of phyllosphere populations caused by NB application could partially
contribute to downy mildew control by competition for space or other biocontrol
strategies. Particularly, changes in the abundance of phyllosphere microorganisms
may provide a contribution to resistance induction, partially affecting the
hormone-mediated signaling pathways involved. Modifying phyllosphere populations
by increasing natural biocontrol agents with the application of selected
nutritional factors can open new opportunities in terms of sustainable plant
protection strategies.
PMID- 27486469
TI - Phytochrome and Ethylene Signaling Integration in Arabidopsis Occurs via the
Transcriptional Regulation of Genes Co-targeted by PIFs and EIN3.
AB - Plant seedlings germinating under the soil are challenged by rough soil grains
that can induce physical damage and sudden exposure to light, which can induce
photobleaching. Seedlings overcome these challenges by developing apical hooks
and by suppressing chlorophyll precursor biosynthesis. These adaptive responses
are, respectively, regulated by the phytochrome and ethylene signaling pathways
via the PHYTOCHROME-INTERACTING FACTORs (PIFs) and the ETHYLENE INSENSITIVE 3
(EIN3)/EIN3-LIKE transcription factors. Although many processes downstream of
phytochrome and ethylene signaling are similar, it remains unclear if and where
these pathways converge. Here, we show PIFs and EIN3 induce similar changes in
the transcriptome without robustly regulating each other's signaling pathways.
PIFs and EIN3 target highly overlapped gene promoters and activate subsets of the
co-target genes either interdependently or additively to induce plant responses.
For chlorophyll biosynthesis, PIFs and EIN3 target and interdependently activate
the expression of HOOKLESS1. HOOKLESS1, in turn, represses chlorophyll synthesis
genes to prevent photobleaching. Thus, our results indicate an integration of the
phytochrome and ethylene signaling pathways at the level of transcriptional gene
regulation by two core groups of transcription factors, PIFs and EIN3.
PMID- 27486470
TI - Corrigendum: Digital Gene Expression Analysis of Populus simonii * P. nigra
Pollen Germination and Tube Growth.
AB - [This corrects the article on p. 825 in vol. 7, PMID: 27379121.].
PMID- 27486471
TI - Rice Stress Associated Protein 1 (OsSAP1) Interacts with Aminotransferase
(OsAMTR1) and Pathogenesis-Related 1a Protein (OsSCP) and Regulates Abiotic
Stress Responses.
AB - Stress associated proteins (SAPs) are the A20/AN1 zinc-finger containing proteins
which can regulate the stress signaling in plants. The rice SAP protein, OsSAP1
has been shown to confer abiotic stress tolerance to plants, when overexpressed,
by modulating the expression of endogenous stress-related genes. To further
understand the mechanism of OsSAP1-mediated stress signaling, OsSAP1 interacting
proteins were identified using yeast two-hybrid analysis. Two novel proteins,
aminotransferase (OsAMTR1) and a SCP/TAPS or pathogenesis-related 1 class of
protein (OsSCP) were found to interact with OsSAP1. The genes encoding OsAMTR1
and OsSCP were stress-responsive and showed higher expression upon abiotic stress
treatments. The role of OsAMTR1 and OsSCP under stress was analyzed by
overexpressing them constitutively in Arabidopsis and responses of transgenic
plants were assessed under salt and water-deficit stress. The OsAMTR1 and OsSCP
overexpressing plants showed higher seed germination, root growth and fresh
weight than wild-type plants under stress conditions. Overexpression of OsAMTR1
and OsSCP affected the expression of many known stress-responsive genes which
were not affected by the overexpression of OsSAP1. Moreover, the transcript
levels of OsSCP and OsAMTR1 were also unaffected by the overexpression of OsSAP1.
Hence, it was concluded that OsSAP1 regulates the stress responsive signaling by
interacting with these proteins which further regulate the downstream stress
responsive gene expression.
PMID- 27486472
TI - Genome-Wide Association Mapping in the Global Diversity Set Reveals New QTL
Controlling Root System and Related Shoot Variation in Barley.
AB - The fibrous root system is a visible sign of ecological adaptation among barley
natural populations. In the present study, we utilized rich barley diversity to
dissect the genetic basis of root system variation and its link with shoot
attributes under well-water and drought conditions. Genome-wide association
mapping of phenotype data using a dense genetic map (5892 SNP markers) revealed
17 putative QTL for root and shoot traits. Among these, at 14 loci the
preeminence of exotic QTL alleles resulted in trait improvements. The most
promising QTL were quantified using haplotype analysis at local and global genome
levels. The strongest QTL was found on chromosome 1H which accounted for root dry
weight and tiller number simultaneously. Candidate gene analysis across the
targeted region detected a crucial amino acid substitution mutation in the
conserved domain of a WRKY29 transcription factor among genotypes bearing major
and minor QTL alleles. Similarly, the drought inducible QTL QRdw.5H (5H, 95.0 cM)
seems to underlie 37 amino acid deletion and substitution mutations in the
conserved domain of two related genes CBF10B and CBF10A, respectively. The
identification and further characterization of these candidate genes will be
essential to decipher genetics behind developmental and natural adaptation
mechanisms of barley.
PMID- 27486473
TI - Sustained Diurnal Stimulation of Cyclic Electron Flow in Two Tropical Tree
Species Erythrophleum guineense and Khaya ivorensis.
AB - The photosystem II (PSII) activity of C3 plants is usually inhibited at noon
associated with high light but can be repaired fast in the afternoon. However,
the diurnal variation of photosystem I (PSI) activity is unknown. Although,
cyclic electron flow (CEF) has been documented as an important mechanism for
photosynthesis, the diurnal variation of CEF in sun leaves is little known. We
determined the diurnal changes in PSI and PSII activities, light energy
dissipation in PSII and the P700 redox state in two tropical tree species
Erythrophleum guineense and Khaya ivorensis grown in an open field. The PSI
activity (as indicated by the maximum quantity of photo-oxidizable P700) was
maintained stable during the daytime. CEF was strongly activated under high light
at noon, accompanying with high levels of non-photochemical quenching (NPQ) and
PSI oxidation ratio. In the afternoon, CEF was maintained at a relatively high
level under low light, which was accompanied with low levels of NPQ and P700
oxidation ratio. These results indicated that CEF was flexibly modulated during
daytime under fluctuating light conditions. Under high light at noon, CEF
dependent generation of proton gradient across the thylakoid membranes (DeltapH)
mainly contributed to photoprotection for PSI and PSII. By comparison, at low
light in the afternoon, the CEF-dependent formation of DeltapH may be important
for PSII repair via an additional ATP synthesis.
PMID- 27486474
TI - The Role of Silicon in Higher Plants under Salinity and Drought Stress.
AB - Although deemed a "non-essential" mineral nutrient, silicon (Si) is clearly
beneficial to plant growth and development, particularly under stress conditions,
including salinity and drought. Here, we review recent research on the
physiological, biochemical, and molecular mechanisms underlying Si-induced
alleviation of osmotic and ionic stresses associated with salinity and drought.
We distinguish between changes observed in the apoplast (i.e., suberization,
lignification, and silicification of the extracellular matrix; transpirational
bypass flow of solutes and water), and those of the symplast (i.e., transmembrane
transport of solutes and water; gene expression; oxidative stress; metabolism),
and discuss these features in the context of Si biogeochemistry and
bioavailability in agricultural soils, evaluating the prospect of using Si
fertilization to increase crop yield and stress tolerance under salinity and
drought conditions.
PMID- 27486475
TI - Dual Function of NAC072 in ABF3-Mediated ABA-Responsive Gene Regulation in
Arabidopsis.
AB - The NAM, ATAF1/2, and CUC2 (NAC) domain proteins play various roles in plant
growth and stress responses. Arabidopsis NAC transcription factor NAC072 has been
reported as a transcriptional activator in Abscisic acid (ABA)-responsive gene
expression. However, the exact function of NAC072 in ABA signaling is still
elusive. In this study, we present evidence for the interrelation between NAC072
and ABA-responsive element binding factor 3 (ABF3) that act as a positive
regulator of ABA-responsive gene expression in Arabidopsis. The transcript of
NAC072 is up-regulated by ABF3 in ABA response, and NAC072 protein interacts with
ABF3. Enhanced ABA sensitivity occurs in nac072 mutant plants that overexpressed
ABF3. However, overexpression of NAC072 weakened the ABA sensitivity in the abf3
mutant plants, but instead of recovering the ABA sensitivity of abf3. NAC072 and
ABF3 cooperate to regulate RD29A expression, but are antagonistic when regulating
RD29B expression. Therefore, NAC072 displays a dual function in ABF3-mediated ABA
responsive gene regulation.
PMID- 27486477
TI - Erratum to: Evaluation of a surgical service in the chronic phase of a refugee
camp: an example from the Thai-Myanmar border.
AB - [This corrects the article DOI: 10.1186/1752-1505-6-5.].
PMID- 27486476
TI - Interferon gamma-induced apoptosis of head and neck squamous cell carcinoma is
connected to indoleamine-2,3-dioxygenase via mitochondrial and ER stress
associated pathways.
AB - BACKGROUND: Tumor response to immunotherapy is the consequence of a concerted
crosstalk between cytokines and effector cells. Interferon gamma (IFNgamma) is
one of the common cytokines coordinating tumor immune response and the associated
biological consequences. Although the role of IFNgamma in the modulation of tumor
immunity has been widely documented, the mechanisms regulating IFNgamma-induced
cell death, during the course of immune therapy, is not described in detail.
RESULTS: IFNgamma triggered apoptosis of CLS-354 and RPMI 2650 cells, enhanced
the protein expression and activation of indoleamine 2,3-dioxygenase (IDO), and
suppressed the basal expression of heme oxygenase-1(HO-1). Interestingly,
IFNgamma induced the loss of mitochondrial membrane potential (Deltapsim) and
increased accumulation of reactive oxygen species (ROS). The cytokine also
induced the activation of Janus kinase (JAK)/Signal Transducer and Activator of
Transcription (STAT)1, apoptosis signal-regulating kinase 1 (ASK1), p38, c-jun-N
terminal kinase (JNK) and NF-kappaB pathways and the transcription factors STAT1,
interferon regulatory factor 1 (IRF1), AP-1, ATF-2, NF-kappaB and p53, and
expression of Noxa protein. Furthermore, IFNgamma was found to trigger
endoplasmic reticulum (ER) stress as evidenced by the cleavage of caspase-4 and
activation of protein kinase RNA-like endoplasmic reticulum kinase (PERK) and
inositol-requiring-1alpha (IRE1alpha) pathways. Using specific inhibitors, we
identified a potential role for IDO as apoptotic mediator in the regulation of
IFNgamma-induced apoptosis of head and neck squamous cell carcinoma (HNSCC) cells
via Noxa-mediated mitochondrial dysregulation and ER stress. CONCLUSION: In
addition to the elucidation of the role of IDO in the modulation of apoptosis,
our study provides new insights into the molecular mechanisms of IFNgamma-induced
apoptosis of HNSCC cells during the course of immune therapy.
PMID- 27486478
TI - Screening for antioxidant and antibacterial activities of phenolics from Golden
Delicious apple pomace.
AB - BACKGROUND: Synthetic antioxidants and antimicrobials are losing ground to their
natural counterparts and therefore, the food industry has motivated to seek other
natural alternatives. Apple pomace, a by-product in the processing of apples, is
rich in polyphenols, and plant polyphenols have been used as food additives owing
to their strong antioxidant and antimicrobial properties. The goal of this study
was to screen the individual polyphenols with antioxidant and antimicrobial
activities from the extracts (methanol, ethanol, acetone, ethyl acetate, and
chloroform) of Golden Delicious pomace. RESULTS: First, the polyphenolic
compounds (total phenol content, TPC; total flavonoids, TFD; total flavanols,
TFL) and antioxidant activities (AAs) with four assays (ferric reducing
antioxidant power, FRAP; 1,1-diphenyl-2-picryhydrazyl radical scavenging capacity
assay, DRSC; hydroxyl radical averting capacity assay, HORAC; oxygen radical
absorbance capacity assay, ORAC) were analyzed. The results showed a significant
positive correlation (P < 0.05) between AAs and TFD. Ethyl acetate extract (EAE)
exhibited the highest TFD with a concentration of 1.85 mg RE/g powder (expressed
as rutin equivalents), and the highest AAs (expressed as butylated hydroxytoluene
(BHT) equivalents) with 2.07 mg BHT/g powder for FRAP, 3.05 mg BHT/g powder for
DRSC, 5.42 mg BHT/g powder for HORAC, and 8.89 mg BHT/g powder for ORAC.
Composition and AA assays of individual polyphenols from the EAE were then
performed. Phloridzin and phloretin accounted for 46.70 and 41.94 % of TFD,
respectively. Phloretin displayed the highest AA, followed by phloridzin.
Finally, the antimicrobial activities of the EAE, phloridzin, and phloretin were
evaluated. EAE displayed good inhibitory activities against Staphylococcus aureus
with a minimum inhibition concentration (MIC) of 1.25 mg/ml and against
Escherichia coli with a MIC of 2.50 mg/ml. Phloridzin and phloretin showed better
inhibitory activities than the EAE, which were MICs of 0.50 and 0.10 mg/ml,
respectively, against S. aureus and MICs of 1.50 and 0.75 mg/ml, respectively,
against E. coli. CONCLUSIONS: Ethyl acetate was the best solvent of choice to
extract natural products to obtain the maximum antioxidant and antibacterial
benefits. Phloridzin and phloretin have the potential to be used as natural
alternatives to synthetic antioxidants and antimicrobials.
PMID- 27486479
TI - Activation of lignocellulosic biomass for higher sugar yields using aqueous ionic
liquid at low severity process conditions.
AB - BACKGROUND: Concerns around greenhouse gas emissions necessitate the development
of sustainable processes for the production of chemicals, materials, and fuels
from alternative renewable sources. The lignocellulosic plant cell walls are one
of the most abundant sources of carbon for renewable bioenergy production.
Certain ionic liquids (ILs) are very effective at disrupting the plant cell walls
of lignocellulose, and generate a substrate that is effectively hydrolyzed into
fermentable sugars. Conventional ILs are relatively expensive in terms of
purchase price, and the most effective imidazolium-based ILs also require energy
intensive processing conditions (>140 degrees C, 3 h) to release >90 %
fermentable sugar yields after saccharification. RESULTS: We have developed a
highly effective pretreatment technology utilizing the relatively inexpensive IL
comprised tetrabutylammonium [TBA](+) and hydroxide [OH](-) ions that generate
high glucose yields (~95 %) after pretreatment at very mild processing conditions
(50 degrees C). The efficiency of [TBA][OH] pretreatment of lignocellulose was
further studied by analyzing chemical composition, powder X-ray diffraction for
cellulose structure, NMR and SEC for lignin dissolution/depolymerization, and
glycome profiling for cell wall modifications. Glycome profiling experiments and
computational results indicate that removal of the noncellulosic polysaccharides
occurs due to the ionic mobility of [TBA][OH] and is the key factor in
determining pretreatment efficiency. Process modeling and energy demand analysis
suggests that this [TBA][OH] pretreatment could potentially reduce the energy
required in the pretreatment unit operation by more than 75 %. CONCLUSIONS: By
leveraging the benefits of ILs that are effective at very mild processing
conditions, such as [TBA][OH], lignocellulosic biomass can be pretreated at
similar efficiency as top performing conventional ILs, such as 1-ethyl-3
methylimidazolium acetate [C2C1Im][OAc], but at much lower temperatures, and with
less than half the IL normally required to be effective. [TBA][OH] IL is more
reactive in terms of ionic mobility which extends removal of lignin and
noncellulosic components of biomass at the lower temperature pretreatment. This
approach to biomass pretreatment at lower temperatures could be transformative in
the affordability and energy efficiency of lignocellulosic biorefineries.
PMID- 27486480
TI - Partial monosomy14q involving FOXG1 and NOVA1 in an infant with microcephaly,
seizures and severe developmental delay.
AB - BACKGROUND: FOXG1 gene mutations have been associated with the congenital variant
of Rett syndrome (RTT) since the initial description of two patients in 2008. The
on-going accumulation of clinical data suggests that the FOXG1-variant of RTT
forms a distinguishable phenotype, consisting mainly of postnatal microcephaly,
seizures, hypotonia, developmental delay and corpus callosum agenesis. CASE
PRESENTATION: We report a 6-month-old female infant, born at 38 weeks of
gestation after in vitro fertilization, who presented with feeding difficulties,
irritability and developmental delay from the first months of life. Microcephaly
with bitemporal narrowing, dyspraxia, poor eye contact and strabismus were also
noted. At 10 months, the proband exhibited focal seizures and required valproic
acid treatment. Array-Comparative Genomic Hybridization revealed a 4.09 Mb
deletion in 14q12 region, encompassing the FOXG1 and NOVA1 genes. The proband
presented similar feature with patients with 14q12 deletions except for
dysgenesis of corpus callosum. Disruption of the NOVA1 gene which promotes the
motor neurons apoptosis has not yet been linked to any human phenotypes and it is
uncertain if it affects our patient's phenotype. CONCLUSIONS: Since our patient
is the first reported case with deletion of both genes (FOXG1-NOVA1), thorough
clinical follow up would further delineate the Congenital Rett-Variant
phenotypes.
PMID- 27486481
TI - A de novo 1.6Mb microdeletion at 19q13.2 in a boy with Diamond-Blackfan anemia,
global developmental delay and multiple congenital anomalies.
AB - BACKGROUD: Microdeletions at 19q13.2 are very rare. Only two cases have been
previously described. Here we report a 2-year-2-month old boy with Diamond
Blackfan anemia, global developmental delay, cognitive impairments, distinctive
facial features, behavior problems, skeletal and genital dysplasia. CASE
PRESENTATION: A de novo 1.6 Mb microdeletion at 19q13.2q13.31 was detected by
chromosomal microarray analysis. Haploinsufficiency of the RPS19 gene is known to
cause Diamond-Blackfan anemia, other features in this patient are likely due to
the deletion of other candidate genes such as PAFAH1B3, ERF, LIPE and GSK3A.
CONCLUSION: The deletion detected in our patient overlapped and was significantly
smaller than the ones previously reported, which offered the opportunity to
further define the critical region for this proposed contiguous gene deletion
syndrome.
PMID- 27486482
TI - A pilot investigation of the prevalence of US-detectable forefoot joint pathology
and reported foot-related disability in participants with systemic lupus
erythematosus.
AB - BACKGROUND: The main aim of this study was to determine the prevalence of US
detectable forefoot bursae, metatarsophalangeal (MTP) joint and
metacarpophalangeal (MCP) joint synovial hypertrophy (SH), Power Doppler (PD)
signal or erosion in participants with systemic lupus erythematosus (SLE). A
secondary aim was to determine the strength of potential association between
patient reported foot-related disability and US-detected forefoot bursae, MTP
joint SH, PD signal or erosion in participants with SLE. METHOD: A cross
sectional observational study of 20 participants with SLE was completed to
determine the prevalence of US-detected forefoot bursal, MTP and MCP joint
pathology. Patient-reported foot-related impairment and activity limitation
(accumulatively referred to as disability) were also recorded. Spearmans' Rank
Correlation analyses were completed to determine the potential strength of
association between US-detected pathology and patient report disability. RESULTS:
The prevalence of MTP joint SH and PD was 80 % (16/20) and 10 % (2/20),
respectively. The prevalence of MCP joint SH and PD was 60 % (12/20) and 30 %
(6/20) respectively. A significant association was noted between PD scores for
the MTP joints and MCP joints (r = 0.556; p = 0.011) although this was not
demonstrated for SH scores (r = 0.176; p = 0.459). Significant associations
between forefoot bursal prevalence and MTP joint PD were noted (r = 0.467; p =
0.038). The prevalence of bursae and bursal PD (grade 2 or above) was 100 %
(20/20) and 10 % (2/20), respectively. Moderate foot-related impairment and
activity limitation was reported by 95 and 85 % of participants respectively.
CONCLUSION: This pilot study suggests that US-detected MTP, MCP joint and
forefoot bursal abnormalities may be prevalent in participants with SLE and they
may experience a moderate level of foot-related disability. Further research is
required to substantiate these preliminary findings.
PMID- 27486483
TI - A quantitative measure of restricted and repetitive behaviors for early
childhood.
AB - BACKGROUND: Restricted and repetitive behaviors are characteristic phenotypic
features of many neurodevelopmental, psychiatric, and neurological conditions.
During early childhood, such behaviors are considered normative. More research is
needed to delineate the dimensions of restricted and repetitive behavior across
typical and atypical development during this period. METHODS: We developed the 34
item parent-rated Repetitive Behavior Scale for Early Childhood (RBS-EC) to
capture quantitative, dimensional features across a broad range of behaviors
contributing to this domain. We evaluated its psychometric properties and factor
structure in a community sample of 914 toddlers. RESULTS: The RBS-EC showed
excellent overall internal consistency (alpha = 0.90), strong test-retest
reliability (ICC = 0.87 for topographies and 0.90 for frequency) and evidence of
convergent and discriminative validity. Using a split-half approach to factor
analysis, we identified that a three- or four-factor structure best fit the data
and confirmatory factor analysis indicated acceptable fit for both models. The
empirically derived four-factor model was consistent with our conceptual model
and included repetitive motor, restricted interests and behavior, ritual and
routine, and self-directed behavior. CONCLUSIONS: This initial study indicates
that the RBS-EC is a reliable and valid instrument for characterizing
quantitative, dimensional aspects of restricted and repetitive behaviors in young
children.
PMID- 27486485
TI - Draft genome sequence of Mycobacterium rufum JS14(T), a polycyclic-aromatic
hydrocarbon-degrading bacterium from petroleum-contaminated soil in Hawaii.
AB - Mycobacterium rufum JS14(T) (=ATCC BAA-1377(T), CIP 109273(T), JCM 16372(T), DSM
45406(T)), a type strain of the species Mycobacterium rufum sp. . belonging to
the family Mycobacteriaceae, was isolated from polycyclic aromatic hydrocarbon
(PAH)-contaminated soil in Hilo (HI, USA) because it harbors the capability of
degrading PAH. Here, we describe the first genome sequence of strain JS14(T),
with brief phenotypic characteristics. The genome is composed of 6,176,413 bp
with 69.25 % G + C content and contains 5810 protein-coding genes with 54 RNA
genes. The genome information on M. rufum JS14(T) will provide a better
understanding of the complexity of bacterial catabolic pathways for degradation
of specific chemicals.
PMID- 27486486
TI - Dr. Alfred A. Bove Lends Expertise on the Impact of Exercise on Cardiovascular
Disease for the Methodist Debakey Cardiovascular Journal.
PMID- 27486484
TI - Prevention of fatigue and insomnia in shift workers-a review of non
pharmacological measures.
AB - BACKGROUND: Excessive fatigue and insomnia are common among shift workers and can
lead to negative effects such as reduced work performance, processing errors,
accidents at work, absenteeism, reduced quality of life, and symptoms of
depression. Moreover, work in rotating shifts can be a risk factor for different
somatic and psychiatric diseases and may contribute to poor health, especially in
elder adults and women. This review aims to show non-pharmacological preventive
measures against fatigue and insomnia in shift workers. METHOD: Computerized
literature searches in MedLine and in the Cochrane Library were performed with
the following key words: shift work disorder, fatigue, insomnia, shift work,
measures, treatment, therapy, strategies and coping. The search was limited to
non-pharmacological studies that were conducted on human subjects and published
as English-language articles in peer-reviewed journals since 1970. Additional
studies were identified through the reference sections of relevant articles.
Eighteen articles on fatigue in shift workers, including six original research
articles with a total sample size of 3504 probands consisting of industrial
workers, office employees, aircraft maintenance engineers, and non-shift workers
working in simulated shifts, were analyzed, as well as seven articles on
insomnia, including an original research article with a sample size of 26 media
workers. Also, 4 reviews on shift work disorder were analyzed. MAIN: The
occurrence of fatigue and insomnia in shift workers associated with a working
period is described as shift work disorder. Estimations on the prevalence of
shift work disorder in shift workers vary between 5 % and about 20 %; about one
in three shift workers is affected by insomnia and up to 90 % of shift workers
report regular fatigue and sleepiness at the workplace. We concluded that there
is a necessity for treatments to improve the sleep quality of the shift working
population. The most common non-pharmacological recommendations to improve sleep
quality and to reduce insomnia and fatigue were scheduling, bright light
exposure, napping, psychoeducation for sleep hygiene, and cognitive-behavioral
measures. CONCLUSION: Some important preventive coping strategies for fatigue
associated with shift work such as napping and exposure to bright light have
already been investigated and are generally approved. A few studies also provide
good evidence for the efficacy of cognitive-behavioral techniques in the
treatment of chronic primary and comorbid insomnia. These coping strategies
summarized in this paper should be considered in the workplace health promotion
programs of each work environment to improve working conditions for shift workers
and to save money.
PMID- 27486487
TI - Exercise and Heart Disease.
PMID- 27486489
TI - Electrocardiographic Evaluation in Athletes and Use of the Seattle Criteria to
Improve Specificity.
AB - The screening of athletes for cardiovascular disease prior to participation can
be challenging. Sustained training often leads to anatomical changes in the heart
that can translate into electrocardiographic (ECG) abnormalities. This can lead
to a high false-positive rate that excludes healthy participants or results in
costly workups. The Seattle Criteria applied to ECG interpretation has resulted
in improved specificity without sacrificing sensitivity. At the Houston Methodist
DeBakey Heart & Vascular Center in Houston, we have had much success using this
tool to screen thousands of athletes ranging across all age groups and levels of
expertise-from the middle school level to the professional athlete.
PMID- 27486488
TI - Sudden Cardiac Death in Athletes.
AB - There are clear health benefits to exercise; even so, patients with cardiac
conditions who engage in exercise and athletic competition may on rare occasion
experience sudden cardiac death (SCD). This article reviews the epidemiology and
common causes of SCD in specific athlete populations. There is ongoing debate
about the optimal mechanism for SCD prevention, specifically regarding the
inclusion of the ECG and/or cardiac imaging in routine preparticipation sports
evaluation. This controversy and contemporary screening recommendations are also
reviewed.
PMID- 27486490
TI - Cardiac Imaging In Athletes.
AB - Athletic heart syndrome refers to the physiological and morphological changes
that occur in a human heart after repetitive strenuous physical exercise.
Examples of exercise-induced changes in the heart include increases in heart
cavity dimensions, augmentation of cardiac output, and increases in heart muscle
mass. These cardiac adaptations vary based on the type of exercise performed and
are often referred to as sport-specific cardiac remodeling. The hemodynamic
effects of endurance and strength training exercise lead to these adaptations.
Any abnormalities in chamber dilatation and left ventricular function usually
normalize with cessation of exercise. Athletic heart syndrome is rare and should
be differentiated from pathologic conditions such as hypertrophic cardiomyopathy,
left ventricular noncompaction, and arrhythmogenic right ventricular dysplasia
when assessing a patient for athletic heart syndrome. This paper describes
specific adaptations that occur in athletic heart syndrome and tools to
distinguish between healthy alterations versus underlying pathology.
PMID- 27486491
TI - Pulmonary Aspects of Exercise and Sports.
AB - Although the lungs are a critical component of exercise performance, their
response to exercise and other environmental stresses is often overlooked when
evaluating pulmonary performance during high workloads. Exercise can produce
capillary leakage, particularly when left atrial pressure increases related to
left ventricular (LV) systolic or diastolic failure. Diastolic LV dysfunction
that results in elevated left atrial pressure during exercise is particularly
likely to result in pulmonary edema and capillary hemorrhage. Data from race
horses, endurance athletes, and triathletes support the concept that the lungs
can react to exercise and immersion stress with pulmonary edema and pulmonary
hemorrhage. Immersion in water by swimmers and divers can also increase stress on
pulmonary capillaries and result in pulmonary edema. Swimming-induced pulmonary
edema and immersion pulmonary edema in scuba divers are well-documented events
caused by the fluid shifts that occur with immersion, elevated pulmonary venous
pressure during extreme exercise, and negative alveolar pressure due to
inhalation resistance. Prevention strategies include avoiding extreme exercise,
avoiding over hydration, and assuring that inspiratory resistance is minimized.
PMID- 27486492
TI - Coming of Age: Considerations in the Prescription of Exercise for Older Adults.
AB - Older adults represent the fastest-growing age demographic of the population.
Physiological changes associated with primary aging and concurrent chronic
disease adversely impact functional capacity, health outcomes, and quality of
life. For these reasons, there is a national emphasis for healthcare providers to
improve the health, function, and quality of life of older adults to preserve
independent living and psychological well-being. The benefits of regular physical
activity or exercise with regard to aging and disease are indisputable, yet many
clinicians do not prescribe exercise to older adults. This reluctance may be
attributable to a lack of knowledge regarding appropriate exercise prescription
for older adults in light of the potential risks and benefits of various doses
and types of exercise. In addition, clinicians and patients may have concerns
about potential health considerations relevant to older adults such as
comprehensive pre-exercise screening and exercise-drug interactions. In light of
this, the following review presents (1) guidelines for exercise prescription in
older adults and modification of these guidelines for patients with the most
common age-associated comorbidities; (2) recommendations for pre-exercise
screening prior to initiating an exercise program in older adults; (3)
considerations for older adults on one or more medications; and (4) common
barriers to adopting and maintaining exercise in an older population. Our goal is
to provide a framework that clinicians can follow when prescribing exercise in
older adults while considering the unique characteristics and concerns present in
this population.
PMID- 27486493
TI - Exercise Intolerance In Heart Failure With Preserved Ejection Fraction.
AB - More than 50% of Americans with heart failure have preserved ejection fraction
(HFpEF). Exercise intolerance is a hallmark of HFpEF, but the pathophysiology is
not well understood. Diverse etiologies and incomplete mechanistic understanding
have resulted in ineffective management strategies to improve the outcomes of
HFpEF. Traditional therapies that have been beneficial in the treatment of heart
failure with reduced ejection fraction (HFrEF), neurohormonal blockade in
particular, have not been effective in treating HFpEF. In this review, we address
underlying mechanisms of HFpEF and present the rationale supporting exercise as a
component of comprehensive management.
PMID- 27486494
TI - Exercise And Heart Failure: Advancing Knowledge And Improving Care.
AB - Exercise limitation is the hallmark of heart failure, and an increasing degree of
intolerance is associated with poor prognosis. Objective evaluation of functional
class (e.g., cardiopulmonary exercise testing) is essential for adequate
prognostication in patients with advanced heart failure and for implementing an
appropriate exercise training program. A graded exercise program has been shown
to be beneficial in patients with heart failure and has become an essential
component of comprehensive cardiac rehabilitation in these patients. An exercise
program tailored to the patient's preferences, possibilities, and physiologic
reserve has the greatest chance of being successful. Despite being safe,
effective, and a guideline-recommended treatment to improve quality of life,
exercise training remains grossly underutilized. Patient, physician, insurance
and practice barriers need to be addressed to improve this quality gap.
PMID- 27486495
TI - Case Report: Cardiac Tumor Resection And Repair With Porcine Xenograft.
AB - Primary cardiac sarcomas are rare and carry a grave prognosis. Improved survival
requires a complete margin negative resection of the tumor. These surgical
resections are often large and complex, requiring extensive reconstructive
procedures. The appropriate material for cardiac reconstruction is not known. We
have used glutaraldehyde-fixed bovine pericardium in our early series but have
recently employed the MatriStem((r)) Surgical Matrix PSMX membrane (ACell((r)),
Inc.; Columbia, MD), a unique proprietary urinary bladder matrix derived from
porcine urinary bladder with the potential for viability and tissue ingrowth. In
our study of six patients at this institution, all six underwent successful
surgical resection and repair with the MatriStem acellular porcine urinary
bladder membrane (ACell). The postoperative course was uncomplicated in all
patients, and they are still alive at this time. An aggressive surgical approach
to cardiac tumors can possibly lead to complete resection but often requires
reconstruction of the cardiac tissue with a membrane. We were able to achieve
acceptable results in our cardiac reconstruction by using the ACell extracellular
matrix to reconstruct the defect following tumor resection. Longer-term follow-up
in these patients, including imaging studies, will be necessary to demonstrate
the durability and integrity of the reconstruction.
PMID- 27486496
TI - Chylous Ascites Following Open Abdominal Aortic Aneurysm Repair: An Unusual
Complication.
AB - Chylous ascites is a rare complication after abdominal aortic aneurysm repair.
Accumulation of chyle within the close space of the peritoneal cavity may cause
severe discomfort to the patient, complicating the postoperative course. Prompt
diagnosis is needed to adopt measures for reducing lymph leakage and contributing
to lymphatic fistula closure. Fortunately, conservative treatment is successful
in the majority of cases. In the rare cases that do not respond to conservative
treatment, surgery becomes mandatory. Accurate preoperative localization of lymph
leakage is a prerequisite for a successful outcome. Postoperative chyloperitoneum
has a benign course and an excellent prognosis.
PMID- 27486497
TI - Contained Rupture of Ventricular Wall And Ventricular Septal Defect In the Same
Patient Following Myocardial Infarction.
PMID- 27486498
TI - Wall of Honor.
PMID- 27486499
TI - Cardiac Consequences Of Electrolyte Imbalance.
PMID- 27486500
TI - Two Poems Introducing Don Quixote.
PMID- 27486501
TI - Bullseye.
PMID- 27486502
TI - Lighting the Way.
PMID- 27486503
TI - Letter to the Editor.
PMID- 27486504
TI - Qualitative evaluation of the adesive interface between lithium disilicate,
luting composite and natural tooth.
AB - Aim of this work was to qualitatively evaluate the interface between tooth,
luting composite and lithium disilicate surface using a scanning electron
microscope (SEM). An extracted restoration-free human molar was stored in
physiological solution until it was embedded in an autopolimerysing acrylic
resin. A standard preparation for overlay was completed and after preparation an
anatomic overlay was waxed on the tooth and then hot pressed using lithium
disilicate ceramic. After cementation the sample was dissected and the section
was analysed using an Automatic Micromet (Remet s.a.s) and the section was
analyzed using a scanning electron microscope (SEM). SEM evaluation of the tooth
showed the three layers seamlessly; by increasing the enlargement the interface
did not change.
PMID- 27486505
TI - Fracture resistance of endodontically treated teeth restored with a bulkfill
flowable material and a resin composite.
AB - AIM: To determine and compare the fracture resistance of endodontically treated
teeth restored with a bulk fill flowable material (SDR) and a traditional resin
composite. METHODS: Thirty maxillary and 30 mandibular first molars were selected
based on similar dimensions. After cleaning, shaping and filling of the root
canals and adhesive procedures, specimens were assigned to 3 subgroups for each
tooth type (n=10): Group A: control group, including intact teeth; Group B:
access cavities were restored with a traditional resin composite (EsthetX;
Dentsply-Italy, Rome, Italy); Group C: access cavities were restored with a bulk
fill flowable composite (SDR; Dentsply-Italy), except 1.5 mm layer of the
occlusal surface that was restored with the same resin composite as Group B. The
specimens were subjected to compressive force in a material static-testing
machine until fracture occurred, the maximum fracture load of the specimens was
measured (N) and the type of fracture was recorded as favorable or unfavorable.
Data were statistically analyzed with one-way analysis of variance (ANOVA) and
Bonferroni tests (P<0.05). RESULTS: No statistically significant differences were
found among groups (P<0.05). Fracture resistance of endodontically treated teeth
restored with a traditional resin composite and with a bulk fill flowable
composite (SDR) was similar in both maxillary and mandibular molars and showed no
significant decrease in fracture resistance compared to intact specimens.
CONCLUSIONS: No significant difference was observed in the mechanical fracture
resistance of endodontically treated molars restored with traditional resin
composite restorations compared to bulk fill flowable composite restorations.
PMID- 27486506
TI - In vitro evaluation of carrier based obturation technique: a CBCT study.
AB - AIM: The goal of the study was to compare the ability of two different carrier
based obturation (CBO) techniques to reach working length and fill in three
dimensions root canal systems, by using CBCT. MATERIALS AND METHODS: Twenty-six
extracted molars were scanned with CBCT and 40 curved canals were selected
(between 30 degrees and 90 degrees ) and divided in two similar groups (n=20).
All canals were prepared up to size 25 taper .06 using nickel-titanium
instrumentation. The canals in the Group SC were obturated using Soft-Core
obturators (Kerr, Romulus, Mi, USA), while Group TH canals (n= 20) were obturated
using Thermafil Endodontic Obturators (Tulsa Dental Products, Tulsa, OK, USA),
strictly following manufacturers' instructions for use. The obturations were
analyzed by means of CBCT to measure the distance from the apical limit of
obturation to the apical foramen and the presence of voids inside root canals.
RESULTS: There was no significant difference between the two groups in the mean
distance of the apical extent of the obturation (t test, p>0.05). Overfilling
occurred in only 3 cases (2 in Group TH and 1 in Group SC). The percentages of
voids in both groups were very low with no significant difference (Z test,
p>0.05). CONCLUSIONS: The two tested CBO techniques showed similar positive
results in terms of performance, even if, after checking with verifiers, in most
cases the size of the selected Soft-Core obturator was one size smaller than
Thermafil.
PMID- 27486507
TI - Biomimetic hydroxyapatite used in the treatment of periodontal intrabony pockets:
clinical and radiological analysis.
AB - AIM: Hydroxyapatite (PA) has a chemical composition and physical structure very
similar to natural bone and therefore it has been considered to be the ideal
biomaterial able to ensure a biomimetic scaffold to use in bone tissue
engineering. The aim of this study is to clinically test hydroxyapatite used as
osteoconductive biomaterial in the treatment of periodontal bone defects.
Clinical and radiological evaluations were conducted at 6, 12 and 18 months after
the surgery. MATERIALS AND METHODS: Forty patients with 2- and 3-wall intrabony
pockets were enrolled in this study. PPD, CAL, radiographic depth (RD) and
angular defects were preoperatively measured. After surgery, patients were re
evaluated every 6 months for 18 months. Statistical analyses were also performed
to investigate any differences between preoperative and postoperative
measurements. RESULTS: Paired t-test samples conducted on the data obtained at
baseline and 18 months after, showed significant (p<0.01) differences in each
measurement performed. The role of preoperative RD was demonstrated to be a
significant key factor (p<0.01). A relevant correlation between preoperative PPD
and CAL gain was also found. CONCLUSIONS: Within the limitations of this study,
the absence of anatomical variables, except the morphology of the bone defect,
emphasizes the importance of the proper surgical approach and the graft material
used.
PMID- 27486509
TI - Histone acetyl transferase GCN5 promotes human hepatocellular carcinoma
progression by enhancing AIB1 expression.
AB - BACKGROUND: General control non-depressible 5 (GCN5) is a crucial catalytic
component of a transcriptional regulatory complex that plays important roles in
cellular functions from cell cycle regulation to DNA damage repair. Although GCN5
has recently been implicated in certain oncogenic roles, its role in liver cancer
progression remains vague. RESULTS: In this study, we report that GCN5 was
overexpressed in 17 (54.8 %) of 31 human hepatocellular carcinoma (HCC)
specimens. Down-regulation of GCN5 inhibited HCC cell proliferation and xenograft
tumor formation. GCN5 knockdown decreased the protein levels of the proliferation
marker proliferating cell nuclear antigen (PCNA) and amplified in breast cancer 1
(AIB1), but increased the protein levels of cell cycle inhibitor p21(Cip1/Waf1)
in HepG2 cells. GCN5 regulated AIB1 expression, at least in part, by cooperating
with E2F1 to enhance AIB1 transcription. Consistently, GCN5 expression was
positively correlated with AIB1 expression in human HCC specimens in two GEO
profile datasets. CONCLUSION: Since AIB1 plays a promoting role in HCC
progression, our results propose that GCN5 promotes HCC progression at least
partially by regulating AIB1 expression. This study implicates that GCN5 might be
a potential molecular target for HCC diagnosis and treatment.
PMID- 27486508
TI - Muscle-specific loss of Bmal1 leads to disrupted tissue glucose metabolism and
systemic glucose homeostasis.
AB - BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and
disruption of circadian rhythms is gaining recognition as a contributing factor
to disease prevalence. This disease is characterized by hyperglycemia and glucose
intolerance and symptoms caused by failure to produce and/or respond to insulin.
The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 %
of postprandial glucose. To address the role of the skeletal muscle molecular
clock to insulin sensitivity and glucose tolerance, we generated an inducible
skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-)). RESULTS: Progressive
changes in body composition (decreases in percent fat) were seen in the iMSBmal1
(-/-) mice from 3 to 12 weeks post-treatment as well as glucose intolerance and
non-fasting hyperglycemia. Ex vivo analysis of glucose uptake revealed that the
extensor digitorum longus (EDL) muscles did not respond to either insulin or 5
aminoimidazole-4-carboxamide ribonucleotide (AICAR) stimulation. RT-PCR and
Western blot analyses demonstrated a significant decrease in mRNA expression and
protein content of the muscle glucose transporter (Glut4). We also found that
both mRNA expression and activity of two key rate-limiting enzymes of glycolysis,
hexokinase 2 (Hk2) and phosphofructokinase 1 (Pfk1), were significantly reduced
in the iMSBmal1 (-/-) muscle. Lastly, results from metabolomics analyses provided
evidence of decreased glycolytic flux and uncovered decreases in some
tricarboxylic acid (TCA) intermediates with increases in amino acid levels in the
iMSBmal1 (-/-) muscle. These findings suggest that the muscle is relying
predominantly on fat as a fuel with increased protein breakdown to support the
TCA cycle. CONCLUSIONS: These data support a fundamental role for Bmal1, the
endogenous circadian clock, in glucose metabolism in the skeletal muscle. Our
findings have implicated altered molecular clock dictating significant changes in
altered substrate metabolism in the absence of feeding or activity changes. The
changes in body composition in our model also highlight the important role that
changes in skeletal muscle carbohydrate, and fat metabolism can play in systemic
metabolism.
PMID- 27486511
TI - Expression of matrix metalloproteinase 2 (MMP-2), E-cadherin and Ki-67 in
metastatic and non-metastatic canine mammary carcinomas.
AB - BACKGROUND: The aim of the study was to demonstrate the immunohistochemical
expression of proteins that affect the metastatic potential of a tumour,
including matrix metalloproteinase 2 (MMP-2) and E-cadherin. Another objective
was to determine their correlation with the expression of the Ki-67 antigen in
metastasizing and non-metastasizing mammary carcinomas in female dogs. The study
was conducted on 32 canine mammary carcinomas (12 metastatic and 20 non
metastatic), classified as simple tubular and tubulopapillary carcinomas.
Immunohistochemistry was performed to evaluate the expression of MMP-2, E
cadherin and Ki-67 antigen. RESULTS: MMP-2 was expressed in 85 % of the non
metastatic tumours and in all the metastatic tumours, while E-cadherin was
expressed in 85 % of the non-metastatic tumours and in 66 % of the metastatic
tumours. The Ki-67 antigen was expressed in 65 % of the non-metastatic tumours
and in 91 % of the metastatic tumours. The mean Ki-67 expression was slightly
higher in tumours that had metastasized (1.5 +/- 0.90 vs 1.1 +/- 0.94; p = 0.22).
A similar relationship was found in terms of the intensity of the MMP-2
expression (2.9 +/- 1.9 vs 2.7 +/- 2.4; p = 0.50). A decrease in the expression
of E-cadherin (2.8 +/- 2.5) was found in metastatic tumours compared to the
expression in non-metastatic tumours (3.2 +/- 2.3). However, these differences
were not statistically significant (p = 0.63). CONCLUSION: We did not show
significant differences in MMP-2, E-cadherin and Ki-67 expression between
metastatic and non-metastatic tumours due to low number of cases studied, however
further experiments are necessary to assess the role of these antigens in the
process of canine mammary tumours metastasis.
PMID- 27486510
TI - The effectiveness and feasibility of an online educational program for improving
evidence-based practice literacy: an exploratory randomized study of US
chiropractors.
AB - BACKGROUND: Online education programs are becoming a popular means to disseminate
knowledge about evidence-based practice (EBP) among healthcare practitioners.
This mode of delivery also offers a viable and potentially sustainable solution
for teaching consistent EBP content to learners over time and across multiple
geographical locations. We conducted a study with 3 main aims: 1) develop an
online distance-learning program about the principles of evidence-based practice
(EBP) for chiropractic providers; 2) test the effectiveness of the online program
on the attitudes, skills, and use of EBP in a sample of chiropractors; and 3)
determine the feasibility of expanding the program for broader-scale
implementation. This study was conducted from January 2013 to September 2014.
METHODS: This was an exploratory randomized trial in which 293 chiropractors were
allocated to either an online EBP education intervention or a waitlist control.
The online EBP program consisted of 3 courses and 4 booster lessons, and was
developed using educational resources created in previous EBP educational
programs at 4 chiropractic institutions. Participants were surveyed using a
validated EBP instrument (EBASE) with 3 rescaled (0 to 100) subscores: Attitudes,
Skills, and Use of EBP. Multiple regression was used to compare groups, adjusting
for personal and practice characteristics. Satisfaction and compliance with the
program was evaluated to assess feasibility. RESULTS: The Training Group showed
modest improvement compared to the Waitlist Group in attitudes (Delta =6.2, p <
.001) and skills (Delta =10.0, p < .001) subscores, but not the use subscore
(Delta = -2.3, p = .470). The majority of participants agreed that the
educational program was 'relevant to their profession' (84 %) and 'was
worthwhile' (82 %). Overall, engagement in the online program was less than
optimal, with 48 % of the Training Group, and 42 % of the Waitlist Group
completing all 3 of the program courses. CONCLUSIONS: Online EBP training leads
to modest improvements in chiropractors' EBP attitudes and skill, but not their
use of EBP. This online program can be delivered to a wide national audience, but
requires modification to enable greater individualization and peer-to-peer
interaction. Our results indicate that it is feasible to deliver an online EBP
education on a broad scale, but that this mode of education alone is not
sufficient for making large changes in chiropractors' use of EBP.
PMID- 27486512
TI - Postoperative respiratory failure necessitating transfer to the intensive care
unit in orthopedic surgery patients: risk factors, costs, and outcomes.
AB - BACKGROUND: Postoperative pulmonary complications in orthopedic surgery patients
have been associated with worse clinical outcomes. Identifying patients with
respiratory risk factors requiring enhanced monitoring and management
modifications is an important part of postoperative care. Patients with
unanticipated respiratory decompensation requiring transfer to the intensive care
unit (ICU) have not been studied in sufficient detail. METHODS: A retrospective
case-control study of elective orthopedic surgery patients (knee, hip, shoulder,
or spine, n = 51) who developed unanticipated respiratory failure (RF)
necessitating transfer to the ICU over a 3-year period was conducted. Controls (n
= 153) were frequency matched to cases by gender, age, and surgical procedure.
Patient and perioperative care factors, clinical outcomes, and cost of care were
examined. RESULTS: Transfer to the ICU occurred within 48 h of surgery in 73 % of
the cases, 31 % required non-invasive ventilation, and 18 % required mechanical
ventilation. Cases had a higher prevalence of chronic obstructive pulmonary
disease (COPD), obstructive sleep apnea (OSA), and regular psychotropic
medication use than controls. Cases received more intravenous opioids during the
first 24 postoperative hours, were hospitalized 4 days longer, had higher in
hospital mortality, and had excess hospitalization costs of US$26,571. COPD, OSA,
preoperative psychotropic medications, and anesthesia time were associated with
risk of RF in a multivariate analysis. CONCLUSIONS: Unanticipated RF after
orthopedic surgery is associated with extended hospitalization, increased
mortality, and higher cost of care. Hospital protocols that include risk factor
assessment, enhanced monitoring, and a cautious approach to opioid use in high
risk patients may reduce the frequency of this complication.
PMID- 27486513
TI - Matched-pair analysis: identification of factors with independent influence on
the development of PTLD after kidney or liver transplantation.
AB - BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) adversely affects
patients' long-term outcome. METHODS: The paired t test and McNemar's test were
applied in a retrospective 1:1 matched-pair analysis including 36 patients with
PTLD and 36 patients without PTLD after kidney or liver transplantation. Matching
criteria were age, gender, indication, type of transplantation, and duration of
follow-up. All investigated PTLD specimen were histologically positive for EBV.
Risk-adjusted multivariable regression analysis was used to identify independence
of risk factors for PTLD detected in matched-pair analysis. The resultant
prognostic model was assessed with ROC-curve analysis. RESULTS: Patients
suffering with PTLD had shorter mean survival (p = 0.004), more episodes of CMV
infections or reactivations (p = 0.042), and fewer recipient HLA A2 haplotypes (p
= 0.007), a tacrolimus-based immunosuppressive regimen (p = 0.052) and higher
dosages of tacrolimus at hospital discharge (Tac dosage) (p = 0.052). Significant
independent risk factors for PTLD were recipient HLA A2 (OR = 0.07, 95 % CI =
0.01-0.55, p = 0.011), higher Tac dosages (OR = 1.29, 95 % CI = 1.01-1.64, p =
0.040), and higher numbers of graft rejection episodes (OR = 0.38, 95 % CI = 0.17
0.87, p = 0.023). The following prognostic model for the prediction of PTLD
demonstrated good model fit and a large area under the ROC curve (0.823): PTLD
probability in % = Exp(y)/(1 + Exp(y)) with y = 0.671 - 1.096 * HLA A2-positive
recipient + 0.151 * Tac dosage - 0.805 * number of graft rejection episodes.
CONCLUSIONS: This study suggests prognostic relevance for recipient HLA A2, CMV,
and EBV infections or reactivations and strong initial tacrolimus-based
immunosuppression. Patients with risk factors may benefit from intensified
screening for PTLD.
PMID- 27486514
TI - Dietary supplementation with a high dose of daidzein enhances the antioxidant
capacity in swine muscle but experts pro-oxidant function in liver and fat
tissues.
AB - BACKGROUND: Although isoflavones are natural dietary antioxidants, they may have
toxicological effects. This study aimed to evaluate the redox system in tissues
of finishing pigs by supplementation with high dose of daidzein (640 mg/kg).
RESULTS: The supplementation of high dose of daidzein for 64 d increased the
activity of superoxide dismutase and total antioxidant capacity in longissimus
muscle but down-regulated the expression of reactive oxygen species (ROS)
producing enzyme NADPH oxidase-2 and cyclooxygenase-2. In contrast, high-level
supplementation with daidzein exerted pro-oxidant changes in back fat, abdominal
fat, liver, and plasma, as reflected by increased contents of malondialdehyde, a
lipid peroxidation product, in these tissues. Furthermore, daidzein
supplementation resulted in higher expression of ROS-producing enzymes, including
NADPH oxidase-1 and cyclooxygenase-1 in liver, 5-lipoxygenase (5-LOX) in backfat
and NADPH oxidase-2 both in abdominal fat and backfat. The supplementation of
daidzein did not affect meat quality parameters in longissimus muscle, including
marbling score, eye muscle areas, intramuscular fat, shear force, drip loss, pH
and meat color. CONCLUSIONS: This experiment suggests that dietary
supplementation of finishing pigs with daidzein at a high dose level improves
redox status in muscle but exerts pro-oxidant effect in liver and fat tissues.
PMID- 27486515
TI - Morphometrics and stable isotopes differentiate wintering populations of a
migratory bird.
AB - BACKGROUND: Describing migratory connectivity in mobile animals is crucial for
understanding the selective pressures acting on different populations throughout
their life cycle. Tracking single individuals has provided valuable data, but for
most species the data available are still spurious and usually limited to a few
individuals. Since different populations of migratory birds can be distinguished
by a combination of morphometric measurements and the isotopic composition of
their feathers, it is possible to measure these parameters on a large sample to
differentiate populations. METHODS: We studied northern wheatears, Oenanthe
oenanthe, captured in their African wintering range and applied discriminant
analyses on morphometric measurements and stable isotope signatures to determine
whether birds found in different areas were distinguishable from each other.
RESULTS: Morphometric and isotopic measurements alone were not sufficient to
discriminate between the birds of ssp. oenanthe from different areas in Africa.
When combining the two measurements, however, assignment to the different groups
became substantially more accurate. Following the discriminant analysis of
morphometrics and delta(2)H, delta(13)C, and delta(15)N isotopes signatures, 19
of 20 oenanthe from Kenya, 15 of 20 oenanthe from Mali/Mauritania, and 19 of 20
oenanthe from Niger were assigned correctly to their wintering area. CONCLUSIONS:
Our results show that birds at different wintering sites can be distinguished
from each other when using a combination of markers. We discuss the possible
breeding origins of these wintering birds.
PMID- 27486516
TI - Factors associated with suicide ideation among subway drivers in Korea.
AB - BACKGROUND: There were several suicide events of subway drivers in Korea. The aim
of this study is to explore work-related factors associated with suicide ideation
among subway drivers. METHODS: We analyzed data from 980 male subway drivers. A
section of the Korean version of the Composite International Diagnostic Interview
(K-CIDI 2.1) was administered by trained interviewers to judge whether a driver
has suicide ideation and to diagnose psychiatric disorders. A questionnaire was
also administered to collect data on sociodemographic characteristics, work
environments, occupational stress, person under train (PUT) experience, and work
related problems. Occupational stress was examined by using the Korean
Occupational Stress Scale (KOSS). Logistic regression was applied to evaluate the
association between work-related factors and suicide ideation among subway
drivers. RESULTS: Regarding work-related problems, conflict with passengers and
sudden stops due to the emergency bell were significantly associated with suicide
ideation. MDD, PTSD, and panic disorder were strongly associated with suicide
ideation. In the analysis of occupational stress, insufficient job control (OR
2.34) and lack of reward (OR 2.52) were associated with suicide ideation even
after being adjusted for psychiatric disorders and other work-related factors.
CONCLUSIONS: Insufficient job control and lack of reward were associated with
suicide ideation among subway drivers. Strategies for drivers to have autonomy
while working and to achieve effort-reward balance should be implemented.
Furthermore, drivers who have experienced negative work-related problems should
be managed appropriately.
PMID- 27486517
TI - The association between perceived discrimination and depression/anxiety disorders
among Korean workers: analysis of the third Korean Working Conditions Survey.
AB - BACKGROUND: Discrimination is a long-standing social problem, and interest in the
health effects of discrimination has been increasing. Unfortunately, Korean
workers experience various types and combinations of discrimination. This study
aimed to examine the association between perceived discrimination and
depression/anxiety disorders among Korean workers. METHODS: Data from 33,530 paid
workers were extracted from the third Korean Working Conditions Survey. The data
included general characteristics, occupational characteristics, perceived
discrimination, and depression/anxiety disorders. To examine the relationship
between perceived discrimination and depression/anxiety disorders, multiple
logistic regression analysis was used to evaluate depression/anxiety disorders as
the dependent variable and perceived discrimination as the independent variable,
after adjusting for relevant general and occupational characteristics. RESULTS:
After adjusting for the relevant general and occupational characteristics, we
observed that male and female workers who had experienced perceived
discrimination exhibited a significantly higher likelihood of having
depression/anxiety disorders. The odds ratios among male and female workers were
3.25 (95 % confidence interval: 2.45-4.32) and 4.56 (95 % confidence interval:
3.45-6.03), respectively. CONCLUSIONS: Perceived discrimination was significantly
related to depression or anxiety disorders among Korean workers. The risk of
depression or anxiety was higher among female workers, compared to male workers.
PMID- 27486518
TI - Impact of obesity on hospital complications and mortality in hospitalized
patients with hyperglycemia and diabetes.
AB - OBJECTIVE: Obesity is associated with increased risk of diabetes, hypertension
and cardiovascular mortality. Several studies have reported increased length of
hospital stay and complications; however, there are also reports of obesity
having a protective effect on health, a phenomenon coined the 'obesity paradox'.
We aimed to investigate the impact of overweight and obesity on complications and
mortality in hospitalized patients with hyperglycemia and diabetes. RESEARCH
DESIGN AND METHODS: This retrospective analysis was conducted on 29 623 patients
admitted to two academic hospitals in Atlanta, Georgia, between January 2012 and
December 2013. Patients were subdivided by body mass index into underweight (body
mass index <18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25-29.9
kg/m(2)) and obese (>30 kg/m(2)). Hyperglycemia was defined as a blood glucose
>10 mmol/L during hospitalization. Hospital complications included a composite of
pneumonia, acute myocardial infarction, respiratory failure, acute kidney injury,
bacteremia and death. RESULTS: A total of 4.2% were underweight, 29.6% had normal
weight, 30.2% were overweight, and 36% were obese. 27.2% of patients had diabetes
and 72.8% did not have diabetes (of which 75% had hyperglycemia and 25% had
normoglycemia during hospitalization). A J-shaped curve with higher rates of
complications was observed in underweight patients in all glycemic groups;
however, there was no significant difference in the rate of complications among
normal weight, overweight, or obese patients, with and without diabetes or
hyperglycemia. CONCLUSIONS: Underweight is an independent predictor for hospital
complications. In contrast, increasing body mass index was not associated with
higher morbidity or mortality, regardless of glycemic status. There was no
evidence of an obesity paradox among inpatients with diabetes and hyperglycemia.
PMID- 27486519
TI - PERS&O (PERsistent Sitagliptin treatment & Outcomes): observational retrospective
study on cardiovascular risk evolution in patients with type 2 diabetes on
persistent sitagliptin treatment.
AB - OBJECTIVES: The UK Prospective Diabetes Study (UKPDS) Risk Engine (RE) provides
the best risk estimates available for people with type 2 diabetes (T2D), so it
was applied to patients on persistent sitagliptin treatment. DESIGN: A 'real
world' retrospective, observational, single-center study. SETTING: The study was
performed in a general hospital in Northern Italy in order: (1) to validate UKPDS
RE in a cohort of Italian participants with T2D without prespecified diabetes
duration, with/without cardiovascular (CV) disease, treated with sitagliptin; (2)
to confirm CV risk gender difference; (3) to evaluate the effect on metabolic
control and on CV risk evolution obtained by 'add-on' persistent sitagliptin
treatment. PARTICIPANTS: Sitagliptin 100 mg once a day was taken by 462
participants with T2D: 170 of them (males: 106; age: 63.6+/-8.8; T2D duration:
11.58+/-7.33; females: 64; age: 65.6+/-7.95; T2D duration 13.5+/-7.9) were
treated for 48 months with the same dosage. INTERVENTIONS: An analysis of
normality was performed both for continuous, and for groups variables on UKPDS RE
percentage values, defining the requirement of a base log10 transformation to
normalize risk factor values for analysis validation. RESULTS: The evaluation of
CV risk evolution by gender (t-test) confirmed the expected statistical
difference (p<0.0001). Sitagliptin obtained significant results after 12 months,
and at the end of the observation, both on metabolic control (expressed by
glycated hemoglobin) and on UKPDS RE. Analysis of variance test revealed a
significant effect on CV risk after 12 months (p=0.003), and after 48 months
(p=0.04). A bivariate correlation analysis revealed a correlation index (r)=0.2
between the two variables (p<0.05). CONCLUSIONS: These 'real-world' data obtained
applying UKPDS RE may reflect patients' and clinicians' interest in realizing
individual CV risk, and its evolution. Sitagliptin-persistent treatment for a
medium-long period obtained an improvement on metabolic control, as well as a
reduction on CV risk.
PMID- 27486520
TI - Peripheral sensory neuropathy is associated with altered postocclusive reactive
hyperemia in the diabetic foot.
AB - OBJECTIVE: This study examined whether the presence of peripheral sensory
neuropathy or cardiac autonomic deficits is associated with postocclusive
reactive hyperemia (reflective of microvascular function) in the diabetic foot.
RESEARCH DESIGN AND METHODS: 99 participants with type 2 diabetes were recruited
into this cross-sectional study. The presence of peripheral sensory neuropathy
was determined with standard clinical tests and cardiac autonomic function was
assessed with heart rate variation testing. Postocclusive reactive hyperemia was
measured with laser Doppler in the hallux. Multiple hierarchical regression was
performed to examine relationships between neuropathy and the peak perfusion
following occlusion and the time to reach this peak. RESULTS: Peripheral sensory
neuropathy predicted 22% of the variance in time to peak following occlusion
(p<0.05), being associated with a slower time to peak but was not associated with
the magnitude of the peak. Heart rate variation was not associated with the
postocclusive reactive hyperemia response. CONCLUSIONS: This study found an
association between the presence of peripheral sensory neuropathy in people with
diabetes and altered microvascular reactivity in the lower limb.
PMID- 27486521
TI - Persistent constipation and abdominal adverse events with newer treatments for
constipation.
AB - BACKGROUND: Clinical trials of several new treatments for opioid-induced
constipation (OIC), chronic idiopathic constipation (CIC) and constipation
predominant irritable bowel syndrome (IBS-C) have focused on differences between
subjects relieved of constipation with placebo and active treatment. Patients and
clinicians however, are more interested in the probability these treatments
provide actual relief of constipation and its associated symptoms. METHODS: We
searched the medical literature using MEDLINE and Cochrane central register of
controlled trials. Randomised, placebo-controlled trials that examined the use of
methylnaltrexone, naloxegol, lubiprostone, prucalopride or linaclotide in adults
with OIC, CIC and IBS-C were eligible for inclusion. The primary efficacy measure
was relief of constipation. Adverse event data for abdominal symptoms were also
analysed. KEY RESULTS AND FINDINGS: 25 publications were included in our
analyses. The proportion of constipated individuals with active treatment was
significantly lower than the proportion with placebo; however, in 15 of these 20
trials analysed, a majority of patients remained constipated with active
treatment. Analyses of adverse event data revealed that the percentage of
participants who experienced abdominal pain, diarrhoea and flatulence with active
treatment was higher than that with placebo in the majority of trials analysed.
CONCLUSIONS: Newer pharmacological treatments for constipation are superior to
placebo in relieving constipation, but many patients receiving active treatment
may remain constipated. In addition, all 5 of the treatments studied are
accompanied by no change or a possible increase in the prevalence of abdominal
symptoms, such as abdominal pain, diarrhoea and flatulence.
PMID- 27486522
TI - Percutaneous endoscopic transgastric jejunostomy (PEG-J): a retrospective
analysis on its utility in maintaining enteral nutrition after unsuccessful
gastric feeding.
AB - BACKGROUND/AIMS: Although percutaneous endoscopic gastrostomy (PEG) is the method
of choice for long-term enteral nutrition, feeding-related adverse events such as
aspiration pneumonia and peristomal leakage can impede the use of PEG.
Percutaneous endoscopic transgastric jejunostomy (PEG-J) using large-bore jejunal
tubes may help by circumventing gastric passage during enteral nutrition and
improving drainage of gastric secretions. METHODS: 20 patients (12 males and 8
females) who received PEG-J after unsuccessful PEG feeding during a 6-year period
in our institution were analysed retrospectively to evaluate the efficacy of
large-bore jejunal feeding tubes in maintaining enteral nutrition. RESULTS: The
median age was 83.5 (71-96) years. The median period between PEG and PEG-J was 33
(14-280) days. Indications were aspiration due to gastro-oesophageal reflux in 18
patients and severe peristomal leakage in 2 patients. Tube placements were
successful in all patients. There were 6 (30%) in-hospital mortalities, with 3
(15%) occurring within 30 days after procedure. CONCLUSIONS: PEG-J can be
performed safely in patients with PEG and may facilitate the maintenance of
enteral nutrition in most of the patients. Patients with unsuccessful PEG feeding
can be offered the option of jejunal feeding before considering termination of
enteral nutrition.
PMID- 27486523
TI - The first cases of collagenous sprue successfully treated with thioguanine.
AB - OBJECTIVE: Collagenous sprue (CS) is a rare form of small bowel enteropathy
characterised by a thickened basement membrane and is, in most of the literature,
reported as part of coeliac disease. Multiple treatment strategies are suggested
in CS, but there is no standardised therapy. The aim of this series is to
describe 4 cases of CS and to propose thioguanine (6-TG) treatment. DESIGN: We
reviewed 4 cases of CS. Data were obtained from our prospective database of
patients referred to our coeliac centre. Evaluation of small bowel biopsies was
performed by an expert pathologist. RESULTS: None of the patients had ever had
coeliac-specific antibodies, and all were negative for HLA-DQ2 and HLA-DQ8
phenotype. Three patients were treated with a combination of 6-TG and budesonide,
and 1 patient received 6-TG only. All patients improved remarkably. Normalisation
of the thickened basement membrane was found in 2 patients and complete
histological improvement including full recovery of villi was found in 1 patient.
In the third patient, the thickened basement membrane was only very focally
recognised. The thickened membrane persisted in the last patient, probably
because of the short time of follow-up. CONCLUSIONS: CS should be separated from
coeliac disease. Based on the lack of typical HLA phenotyping and the absence of
coeliac-specific antibodies, there seems to be no relation with coeliac disease
in these 4 cases. A promising treatment option might be 6-TG with or without
budesonide. Research in a larger cohort is needed to standardise treatment for
CS.
PMID- 27486524
TI - Impact of etanercept tapering on work productivity in patients with early
rheumatoid arthritis: results from the PRIZE study.
AB - OBJECTIVE: To assess changes in work productivity in patients who have achieved
response using etanercept (ETN) 50 mg+methotrexate (MTX) (phase I) are randomised
to ETN 25 mg+MTX versus MTX versus placebo (phase II) and then withdrawn from
treatment (phase III). METHODS: Patients included in the analysis were in
employment entering phase II of the PRIZE trial and had one or more follow-ups.
Phase II was a 39-week, randomised and double-blind comparison of the 3 dose
reduction treatments. Phase III was a 26-week observational study where treatment
was withdrawn. The Valuation of Lost Productivity was completed approximately
every 13 weeks to estimate productivity impacts from a societal perspective.
RESULTS: A total of 120 participants were included in our analyses. During phase
II, ETN25+MTX or MTX improved paid work productivity by over 100 hours compared
with placebo, amounting to a gain of ?1752 or ?1503, respectively. ETN25+MTX
compared with placebo gains ?1862 in total paid/unpaid productivity. At week 52,
the 3-month paid work productivity loss was 21.8, 12.8 and 14.0 hours,
respectively. The productivity loss increased at week 64 from week 52, dropped at
week 76 for all treatment groups and then continued rising after week 76 for the
placebo group (71.9 hours at week 91) but not for the other 2 groups (21.9 hours
for ETX25+MTX and 27.6 hours for MTX). CONCLUSIONS: The work productivity gain in
phase I as a result of ETN50+MTX was marginally lost in the dose-reduction
treatment groups, ETN25+MTX and MTX, but substantially lost in the placebo group
during phase II. TRIAL REGISTRATION NUMBER: NCT00913458; Results.
PMID- 27486525
TI - Responsiveness of a simple RAPID-3-like index compared to disease-specific BASDAI
and ASDAS indices in patients with axial spondyloarthritis.
AB - OBJECTIVE: To evaluate the responsiveness of a simple routine assessment of
patient index data (RAPID3)-like index that includes only 3 patient self-report
measures (physical function, pain and patient global estimate) compared to that
of traditional composite indices to assess change in patients with axial
spondyloarthritis (Ax-SpA). METHODS: Devenir des Spondylarthropathies
Indifferenciees Recentes (DESIR) is a prospective cohort of patients with
inflammatory back pain suggestive of Ax-SpA. The study included 461 patients, who
met the Assessment of SpondyloArthritis International Society (ASAS)
classification criteria for Ax-SpA. A simple RAPID3-like index was compared with
the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the AS
Disease Activity Score (ASDAS) scores for responsiveness over 6 months. Construct
validity was also evaluated through Pearson correlations and discrimination of
disease activity through standardised mean differences for the 3 indices.
RESULTS: The RAPID3-like index was correlated significantly with BASDAI (r=0.84,
p<0.005) and ASDAS-C-reactive protein (CRP) (r=0.74, p<0.005), similar to
correlations of BASDAI with ASDAS-CRP (r=0.76, p<0.005). The percentage of
patients with inactive disease ranged from 9% to 25% and with high activity from
10% to 45%, according to various measures. The capacity to discriminate between
high and low disease activity was similar for the 3 indices. The strength of
agreement of RAPID3 with ASDAS-CRP was moderate (0.44) and lower with BASDAI
(0.37). Responsiveness over 6 months was slightly higher for ASDAS-CRP and the
RAPID3-like index than that for BASDAI. CONCLUSIONS: The RAPID3-like index
provides similar information to BASDAI and ASDAS-CRP concerning responsiveness
over 6 months. RAPID3 appears feasible to assess patients with Ax-SpA
quantitatively over time in busy clinical settings.
PMID- 27486526
TI - Osteoporosis prevention among chronic glucocorticoid users: results from a public
health insurance database.
AB - INTRODUCTION: Long-term glucocorticoid therapy is the leading cause of secondary
osteoporosis. The management of glucocorticoid-induced osteoporosis (GIOP) seems
to be inadequate in many European countries. OBJECTIVE: To evaluate the rate of
screening and treatment of GIOP. DESIGN: Information was collected from a
national public health-insurance database in our geographic area of Provence
Alpes-Cote-d'Azur and in Corsica, from September 2009 through August 2011.
PATIENTS: We identified participants aged 15 years and over starting
glucocorticoid therapy (>=7.5 mg of prednisone equivalent per day during at least
90 days consecutive). This cohort was compared with an age-matched and sex
matched population that did not receive glucocorticoids. MAIN OUTCOME MEASURES:
Bone mass, prescription of bone antiresorptive medication and use of calcium
and/or vitamin D treatment. RESULTS: We identified 32 812 patients who were
prescribed glucocorticoid therapy, yielding 1% prevalence. Incidence of
glucocorticoid therapy was 2.8/1000 inhabitants/year. Males represented 44%, the
mean age was 58 years. The median prednisone-equivalent dose was 11 mg/day (IQR 9
18 mg/day). 8% underwent bone mass measurement. Calcium and/or vitamin D, and
bisphosphonates were prescribed in 18% and 12%, respectively. Results were lower
for the control population: 3% underwent bone mass measurement and 3% received
bisphosphonate therapy. The rates of osteodensitometry and treatments were higher
in women over 55 years of age than in men and women 55 years of age and younger,
and also when glucocorticoid therapy was initiated by a rheumatologist versus
other physician specialty. CONCLUSIONS: The management of GIOP remains very
inadequate, despite the availability of a statutory health insurance system.
Targeted interventions are needed to improve the management of GIOP.
PMID- 27486527
TI - Treatment of systemic sclerosis: is there any hope for the future?
PMID- 27486528
TI - Average symptom trajectories following incident radiographic knee osteoarthritis:
data from the Osteoarthritis Initiative.
AB - INTRODUCTION: Previous research has identified the existence of a prodromal phase
of symptom worsening beginning on average 2-3 years prior to the first appearance
of radiographic knee osteoarthritis (OA). The current study extends these
observations to investigate the trajectory of self-reported pain, stiffness,
function and other symptoms following the incidence of radiographic OA. METHODS:
Data were from the incidence cohort of the Osteoarthritis Initiative public use
data sets. Cases were defined as knees without symptoms at enrolment, which
developed incident radiographic OA (Kellgren and Lawrence grade >=2) at any of
the first 4 annual follow-up visits. Symptoms investigated were knee-specific
Western Ontario & McMaster Universities Osteoarthritis Index and Knee injury and
Osteoarthritis Outcome Score subscale scores and individual items, available up
to 3 years before and 5 years after the incidence of radiographic OA.
Trajectories of having at least one of the symptoms from a subscale, and for each
individual symptom over time, were fitted using multilevel logistic regression
models. RESULTS: The probability of symptoms following the initial prodromal
phase generally stabilised, whereas the probability of moderate, severe or
extreme symptoms was consistently low. Two exceptions were pain frequency, which
increased greatly in the lead up to incidence, then decreased slightly, and
audible joint sounds, which had a much higher overall probability, and after
increasing prior to incident radiographic OA, stabilised then started to increase
again at 5 years. CONCLUSIONS: Following an increase in the risk of symptoms
during the prodromal phase, this risk does not continue to increase in the period
up to 5 years after the incidence of radiographic OA.
PMID- 27486529
TI - Irritability in Pediatric Patients: Normal or Not?
AB - The goal of this article is to describe the concept of irritability in children
and youth, which has been revisited in the DSM-5. Traditionally, this behavior
has been more commonly associated with mood disorders, which may account for the
rising incidence of bipolar disorder diagnosis and overuse of mood-stabilizing
medications in pediatric patients. While not predictive of mania, persistent
nonepisodic irritability, if undetected, may escalate to violent behavior with
potentially serious outcomes. It is therefore important to educate clinicians
about how to accurately assess irritability in pediatric patients.
PMID- 27486530
TI - Intravenous Methylprednisolone-Induced Nocturnal Sinus Bradycardia in a Multiple
Sclerosis Patient.
PMID- 27486531
TI - Cerebellar Cognitive Affective Syndrome: A Case Report.
PMID- 27486532
TI - A Case of Risperidone Overdose in a 4-Year-Old Boy.
PMID- 27486533
TI - New-Onset Visual Hallucinations With Eszopiclone.
PMID- 27486534
TI - A Retrospective Snapshot of Patients Prescribed Acute Versus Chronic Narcotic
Therapy in a Resident-Provider Internal Medicine Outpatient Clinic.
PMID- 27486535
TI - Cotard Syndrome: "I'm Dead, So Why Do I Need to Eat?".
PMID- 27486536
TI - Will Adding Methadone to Controlled Substance Monitoring Programs Help
Psychiatrists Prevent Prescription Drug Overdoses?
PMID- 27486537
TI - Postpartum Eclampsia Associated With Changes of Mood Symptoms.
PMID- 27486538
TI - A Survey of Same-Sex Sexual Experiences Among Psychiatric Inpatients With and
Without Borderline Personality Symptomatology.
PMID- 27486539
TI - Delusional Infestation: A Case of Ekbom Syndrome in an HIV-Infected Patient.
PMID- 27486540
TI - Mania Induced by Garcinia cambogia: A Case Series.
PMID- 27486541
TI - Pattern of Care Before Presentation Among the Psychiatric Emergency Cases at a
Tertiary Health Care Center in Nigeria.
AB - OBJECTIVE: To determine the pattern of care sought in cases of psychiatric
emergency before presentation to a tertiary health care center. METHOD:
Consecutive recruitment of 180 emergency psychiatric cases, which comprised a
total of 156 patients, presenting to the accident and emergency unit of the
University of Benin Teaching Hospital (UBTH), Edo State, Nigeria, was conducted
from June 2008 to January 2009. A structured instrument was used to gather the
patients' information including their sociodemographic characteristics, their
care before presentation, and the relations accompanying them to the hospital.
RESULTS: The mean +/- SD patient age was 33.82 +/- 12.64 years, with an age range
of 18-73 years and a modal age of 23 years. The male to female ratio was 1:1.05.
Of the patients, 121 (77.6%) were not married, while 35 (22.4%) were married.
Most identified as Christian (96.2%). The majority of the patients (70.0%)
presented to the hospital through self-referral. Eighty (44.4%) of the patients
had not sought any treatment before coming to UBTH. Forty-seven patients (26.1%)
had sought care in churches, 39 (21.7%) had sought treatment in other hospitals,
and 12 (6.7%) had sought traditional care before presenting to UBTH. Seventy-four
patients (41.1%) were accompanied by parents and 44 (24.4%) were accompanied by
siblings, while the spouse accompanied 23 (12.8%) patients. CONCLUSIONS: Most
patients with psychiatric emergencies at UBTH prefer to present directly to the
tertiary health care center in Benin City, and they are usually supported by
their immediate family members.
PMID- 27486542
TI - Development of the 7-Item Binge-Eating Disorder Screener (BEDS-7).
AB - OBJECTIVE: Develop a brief, patient-reported screening tool designed to identify
individuals with probable binge-eating disorder (BED) for further evaluation or
referral to specialists. METHODS: Items were developed on the basis of the DSM-5
diagnostic criteria, existing tools, and input from 3 clinical experts (January
2014). Items were then refined in cognitive debriefing interviews with
participants self-reporting BED characteristics (March 2014) and piloted in a
multisite, cross-sectional, prospective, noninterventional study consisting of a
semistructured diagnostic interview (to diagnose BED) and administration of the
pilot Binge-Eating Disorder Screener (BEDS), Binge Eating Scale (BES), and RAND
36-Item Short-Form Health Survey (RAND-36) (June 2014-July 2014). The sensitivity
and specificity of classification algorithms (formed from the pilot BEDS item
level responses) in predicting BED diagnosis were evaluated. The final algorithm
was selected to minimize false negatives and false positives, while utilizing the
fewest number of BEDS items. RESULTS: Starting with the initial BEDS item pool
(20 items), the 13-item pilot BEDS resulted from the cognitive debriefing
interviews (n = 13). Of the 97 participants in the noninterventional study, 16
were diagnosed with BED (10/62 female, 16%; 6/35 male, 17%). Seven BEDS items
(BEDS-7) yielded 100% sensitivity and 38.7% specificity. Participants correctly
identified (true positives) had poorer BES scores and RAND-36 scores than
participants identified as true negatives. CONCLUSIONS: Implementation of the
brief, patient-reported BEDS-7 in real-world clinical practice is expected to
promote better understanding of BED characteristics and help physicians identify
patients who may have BED.
PMID- 27486543
TI - Factors Differentiating Childhood-Onset and Adolescent-Onset Schizophrenia:A
Claims Database Study.
AB - BACKGROUND: The greater severity and burden of illness in individuals with early
onset schizophrenia (ie, before age 18 years) deserves further investigation,
specifically regarding its prevalence in community-based treatment and its
association with other psychiatric or medical conditions. METHOD: A retrospective
cohort design was employed using the South Carolina Medicaid claims database
covering outpatient and inpatient medical services from January 1, 1999, through
December 31, 2013, to identify patients aged <= 17 years with a diagnosis of
schizophrenia spectrum disorders (ICD-9-CM). Logistic regression was used to
examine the factors differentiating childhood- versus adolescent-onset
schizophrenia in a community-based system of care. RESULTS: Early onset
schizophrenia was diagnosed in 613 child and adolescent cases during the study
epoch or 0.2% of this population-based cohort. The early onset cohort was
primarily male (64%) and black (48%). The mean length of time followed in the
Medicaid dataset was 12.6 years. Within the early onset cohort, 22.5% were
diagnosed at age <= 12 years and 77.5% were diagnosed as adolescents. The
childhood-onset subgroup was twice as likely to have speech, language, or
educational disabilities and an attention-deficit/hyperactivity disorder
diagnosis but significantly less likely to have schizophrenia or schizoaffective
disorder, an organic brain disorder or mental retardation/intellectual
disability, or a substance use disorder (adjusted OR = 2.01, 2.26, 0.38, 0.31,
0.47, and 0.32, respectively) compared to the adolescent-onset subgroup.
CONCLUSION: Primary care providers should identify and maintain surveillance of
cases of pediatric neurodevelopmental disorders, which appear to be highly
comorbid and genetically related, and refer them early and promptly for
specialized treatment.
PMID- 27486545
TI - Managing Depression Among Homeless Mothers: Pilot Testing an Adapted
Collaborative Care Intervention.
AB - OBJECTIVE: Although depression is common among homeless mothers, little progress
has been made in testing treatment strategies for this group. We describe pilot
test results of an adapted collaborative care model for homeless mothers with
depression. METHOD: We conducted a pilot intervention study of mothers screening
positive for depression in 2 randomly selected shelter-based primary care clinics
in New York over 18 months in 2010-2012. Study participants completed a
psychosocial, health, and mental health assessment at baseline, 3 months, and 6
months. RESULTS: One-third of women screened positive for depression (123 of 328
women). Sixty-seven women (63.2% of the eligible sample) enrolled in the
intervention. At 6 months, compared to usual-care women, intervention group women
were more likely to be receiving depression treatment (40.0% vs 5.9%, P = .01)
and antidepressant medication (73.3% vs 5.9%, P = .001, respectively) and had
more primary care physician and care manager visits at both 3 months (74.3% vs
53.3%, P = .009 and 91.4% vs 26.7%, P < .001, respectively) and 6 months (46.7%
vs 23.5%, P = .003 and 70% vs 17.7%, P = .001, respectively). More women in the
intervention group compared to usual-care women reported >= 50% improvement in
depression symptoms at 6 months (30% vs 5.9%, P = .07). CONCLUSIONS: This pilot
study found that implementing an adapted collaborative care intervention was
feasible in a shelter-based primary care clinic and had promising results that
require further testing. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
NCT02723058.
PMID- 27486544
TI - Post Hoc Analyses of Anxiety Measures in Adult Patients With Generalized Anxiety
Disorder Treated With Vilazodone.
AB - OBJECTIVE: To investigate vilazodone, currently approved for major depressive
disorder in adults, for generalized anxiety disorder (GAD). METHOD: Three
randomized, double-blind, placebo-controlled studies showing positive results for
vilazodone (2,040 mg/d) in adult patients with GAD (DSM-IV-TR) were pooled for
analyses; data were collected from June 2012 to March 2014. Post hoc outcomes in
the pooled intent-to-treat population (n = 1,462) included mean change from
baseline to week 8 in Hamilton Anxiety Rating Scale (HARS) total score, psychic
and somatic anxiety subscale scores, and individual item scores; HARS response
(>= 50% total score improvement) and remission (total score <= 7) at week 8; and
category shifts, defined as HARS item score >= 2 at baseline (moderate to very
severe symptoms) and score of 0 at week 8 (no symptoms). RESULTS: The least
squares mean difference was statistically significant for vilazodone versus
placebo in change from baseline to week 8 in HARS total score (-1.83, P < .0001)
and in psychic anxiety (-1.21, P < .0001) and somatic anxiety (-0.63, P < .01)
subscale scores; differences from placebo were significant on 11 of 14 HARS items
(P < .05). Response rates were higher with vilazodone than placebo (48% vs 39%, P
< .001), as were remission rates (27% vs 21%, P < .01). The percentage of
patients who shifted to no symptoms was significant for vilazodone on several
items: anxious mood, tension, intellectual, depressed mood, somatic-muscular,
somatic-sensory, cardiovascular, respiratory, and autonomic symptoms (P < .05).
CONCLUSIONS: Treatment with vilazodone versus placebo was effective in adult GAD
patients, with significant differences between treatment groups found on both
psychic and somatic HARS items. TRIAL REGISTRATION: ClinicalTrials.gov
identifiers: NCT01629966, NCT01766401, NCT01844115.
PMID- 27486546
TI - A Cross-Sectional Study on the Prevalence, Risk Factors, and Ill Effects of
Internet Addiction Among Medical Students in Northeastern India.
AB - OBJECTIVE: To evaluate Internet addiction among medical students in northeastern
India and gain detailed knowledge about the prevalence, risk factors, and ill
effects commonly associated with the disorder. METHOD: The cross-sectional study
sample comprised 188 medical students from Silchar Medical College and Hospital
(Silchar, Assam, India). Students completed a sociodemographic form and an
Internet use questionnaire, both created for this study, and the Young's 20-Item
Internet Addiction Test after they received brief instructions. Data were
collected during a10-day period in June 2015. RESULTS: Of the 188 medical
students, 46.8% were at increased risk of Internet addiction. Those who were
found to be at increased risk had longer years of Internet exposure (P = .046)
and always online status (P = .033). Also, among this group, the men were more
prone to develop an online relationship. Excessive Internet usage also led to
poor performance in college (P < .0001) and feeling moody, anxious, and depressed
(P < .0001). CONCLUSIONS: The ill effects of Internet addiction include
withdrawal from real-life relationships, deterioration in academic activities,
and a depressed and nervous mood. Internet use for nonacademic purposes is
increasing among students, thus there is an immediate need for strict supervision
and monitoring at the institutional level. The possibility of becoming addicted
to the Internet should be emphasized to students and their parents through
awareness campaigns so that interventions and restrictions can be implemented at
the individual and family levels.
PMID- 27486547
TI - Pharmacotherapy for Insomnia in Primary Care.
AB - Pharmacotherapy for insomnia in primary care settings can be challenging.
Frequently, there are multiple coexisting medical and psychiatric conditions,
drug interactions, concern regarding use of habit-forming sleep aids, and paucity
of time in office visits to discuss management of sleep difficulties. This
article reports the results of a literature search related to pharmacotherapy for
insomnia and presents 4 clinical vignettes with corresponding treatment options.
PMID- 27486548
TI - Two For the Road.
PMID- 27486549
TI - Psychosis Resulting From Herbs Rather Than Nutrients.
PMID- 27486550
TI - Dietary Supplement Nomenclature.
PMID- 27486551
TI - Improvement of sensitivity in continuous wave near infra-red spectroscopy systems
by using silicon photomultipliers.
AB - We experimentally analyze the signal-to-noise ratio of continuous wave (CW) near
infrared spectroscopy (NIRS) reflectance systems based on light emitting diodes
and silicon photomultipliers for high performance low cost NIRS biomedical
systems. We show that under suitable experimental conditions such systems exhibit
a high SNR, which allows an SDS of 7 cm, to our knowledge the largest ever
demonstrated in a CW-NIRs system.
PMID- 27486552
TI - Beyond Contact Tracing: Community-Based Early Detection for Ebola Response.
AB - INTRODUCTION: The 2014 Ebola outbreak in West Africa raised many questions about
the control of infectious disease in an increasingly connected global society.
Limited availability of contact information made contact tracing diffcult or
impractical in combating the outbreak. METHODS: We consider the development of
multi-scale public health strategies that act on individual and community levels.
We simulate policies for community-level response aimed at early screening all
members of a community, as well as travel restrictions to prevent inter-community
transmission. RESULTS: Our analysis shows the policies to be effective even at a
relatively low level of compliance and for a variety of local and long range
contact transmission networks. In our simulations, 40% of individuals conforming
to these policies is enough to stop the outbreak. Simulations with a 50%
compliance rate are consistent with the case counts in Liberia during the period
of rapid decline after mid September, 2014. We also find the travel restriction
to be effective at reducing the risks associated with compliance substantially
below the 40% level, shortening the outbreak and enabling efforts to be focused
on affected areas. DISCUSSION: Our results suggest that the multi-scale approach
can be used to further evolve public health strategy for defeating emerging
epidemics.
PMID- 27486553
TI - Validation of a Tablet as a Tangent Perimeter.
AB - PURPOSE: To describe a tangent perimeter developed on an Apple iPad (Melbourne
Rapid Field, MRF). METHODS: The MRF assays 66 locations over 28 degrees * 18
degrees by having the patient vary fixation. Spot size and background luminance
are paired to yield constant thresholds across the field. Spot locations were
selected after analysis of 360 patient records. The capacity of the MRF to detect
defects was verified in five participants (age 22-28 years) by simulating four
common losses: central, arcuate, quadrant, and hemianopia. We also consider the
effect of: myosis, blur (+3 DS), viewing distance (25-75 cm), ambient light (4
600 lux), and retest repeatability (1-week apart) on thresholds. Group means
[SEM] are compared by Student's t-test and repeatability returned from Bland
Altman analysis. RESULTS: We found a 5 cd.m-2 background replicates the Weber
fraction produced by a Humphrey spot shown at 35 dB. Our variable size gives
constant thresholds (29.6 [0.2] dB) across all locations. Altering viewing
distance (25 cm = 29.8 [0.9] dB; 75 cm = 28.9 [0.6] dB) and ambient lighting (4
lux, 29.8 [0.8] dB; 600 lux, 29.5 [1.0] dB) did not affect threshold although
screen reflections must be avoided. Myosis (-1.2 dB) and blur (-1.5 dB) will
reduce sensitivity (P < 0.05). Simulated defects with a mean defect (MD) of -3.3
dB are detected by the MRF. The Coefficient of repeatability was 9.6% (SD ~2.9
dB) in normal regions and 48.1% (SD ~8.0 dB) in areas of simulated scotoma.
CONCLUSIONS: Tablet technology can return efficient and reliable thresholds to 30
degrees as a tangent perimeter. TRANSLATIONAL RELEVANCE: The MRF will allow
testing at a bedside, at home, in rural or remote areas, or where equipment
cannot be financed.
PMID- 27486554
TI - Comparison of Peristat Online Perimetry with the Humphrey Perimetry in a Clinic
Based Setting.
AB - PURPOSE: We determined the receiver operating characteristic (ROC) curves for
Peristat online perimetry at detecting varying degrees of glaucoma and the
correlation between Peristat online perimetry and Humphrey visual field. METHODS:
A prospective, comparative study of Peristat online perimetry (an achromatic
static computer threshold testing program) and Humphrey visual field (HVF) 24-2
SITA standard testing was performed by 63 glaucoma patients and 30 healthy
controls in random order. The number of total adjacent abnormal test points were
identified for each test, and compared with Spearman correlation. Receive
operating characteristic curves were generated for Peristat online perimetry
detection of mild and moderate-severe glaucoma patients using contrast
sensitivity thresholds of -16.7, -21.7, and -26.7 dB. RESULTS: The area under the
ROC curve for glaucoma detection ranged from 0.77 to 0.81 for mild disease (mean
deviation [MD], >-6 dB on HVF) and 0.85 to 0.87 for moderate to severe disease
(MD, <-6 dB on HVF) depending on contrast threshold. Peristat online perimetry
and Humphrey visual field abnormal points were highly correlated with Spearman
rank correlations ranging from 0.55 to 0.77 (all P < 0.001). CONCLUSIONS:
Peristat online perimetry exhibits a reasonable ROC curve without specialized
equipment and exhibited significant correlation with the conventional 24 degrees
Humphrey visual field test. TRANSLATIONAL RELEVANCE: Low cost widely available
internet-based visual fields may complement traditional office-based visual field
testing.
PMID- 27486555
TI - Local Variability of Macular Thickness Measurements With SD-OCT and Influencing
Factors.
AB - PURPOSE: To compare the intrasession variability of spectral-domain optical
coherence tomography (SD-OCT)-derived local macular thickness measures and
explore influencing factors. METHODS: One hundred two glaucomatous eyes (102
patients) and 21 healthy eyes (21 subjects) with three good quality macular
images during the same session were enrolled. Thickness measurements were
calculated for 3 degrees superpixels for the inner plexiform (IPL), ganglion
cell (GCL), or retinal nerve fiber layers (mRNFL), GC/IPL, ganglion cell complex,
and full macular thickness. Spatial distribution and magnitude of measurement
errors (ME; differences between the 3 individual superpixel values and their
mean) and association between MEs and thickness, age, axial length, and image
quality were explored. RESULTS: MEs had a normal distribution with mostly random
noise along with a small fraction of outliers (1.2%-6.6%; highest variability in
mRNFL and on the nasal border) based on M-estimation. Boundaries of 95%
prediction intervals for variability reached a maximum of 3 MUm for all layers
and diagnostic groups after exclusion of outliers. Correlation between proportion
of outliers and thickness measures varied among various parameters. Age, axial
length, or image quality did not influence MEs (P > 0.05 for both groups).
CONCLUSIONS: Local variability of macular SD-OCT measurements is low and uniform
across the macula. The relationship between superpixel thickness and outlier
proportion varied as a function of the parameter of interest. TRANSLATIONAL
RELEVANCE: Given the low and uniform variability within and across eyes,
definition of an individualized 'variability space' seems unnecessary. The
variability measurements from this study could be used for designing algorithms
for detection of glaucoma progression.
PMID- 27486557
TI - Sun protection practices in New Zealand secondary schools: a 2014 baseline study.
AB - OBJECTIVE: Guided by the established primary school SunSmart programme, a survey
of secondary schools' sun protection policies, planning, behavioural
expectations, curriculum content and environment was undertaken in order to
establish a baseline to inform advocacy and secondary level programme
development. METHODS: All 448 principals of state or state integrated public
secondary schools identified from the Ministry of Education database were mailed
a hard copy questionnaire. School sun protection practices were assessed and a
summative, non-weighted, 11-item Total Sun Protection Score (TSPS) was created.
Associations between TSPS and socio-demographic factors, as well as school sun
protection policy, were investigated using unadjusted and multiple linear
regressions. RESULTS: Usable responses received from 211 of the 448 schools (47%
participation) indicated reasonable representativeness of eligible schools, but
under-representation of low socioeconomic decile institutions (p = 0.003) and
those with the smallest roll size (p = 0.004). Only 50% of schools reported
having a sun protection policy. The least attained TSPS components were outdoor
event planning (17.1%), student breaks (16.6%), sun-protective clothing (8.5%)
and shade provision (6.2%). The mean (SD) TSPS was 4.58 (2.06). In multivariable
analysis, TSPS was statistically significantly positively associated with having
a sun protection policy (p < 0.001) and the presence of primary level classes (p
< 0.001) - the latter suggesting a possible influence of programme continuity,
but negatively associated with integrated school status (p = 0.036). CONCLUSION:
A standard SunSmart programme could be promoted to all schools, irrespective of
socioeconomic decile, overall roll size, gender status or regional population
density. Low attainment of some TSPS components indicates targeting priorities.
PMID- 27486556
TI - Efficacy and Safety of Human Retinal Progenitor Cells.
AB - PURPOSE: We assessed the long-term efficacy and safety of human retinal
progenitor cells (hRPC) using established rodent models. METHODS: Efficacy of
hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats
immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of
dexamethasone, this drug was omitted from a subsequent dose-ranging study, where
different hRPC doses were tested for their ability to preserve visual function
(measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to
6 months after grafting. Safety of hRPC was assessed by subretinal
transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at
3 to 6 and 9 months after grafting, respectively. RESULTS: The optimal dose of
hRPC for preserving visual function/retinal structure in dystrophic rats was
50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in
dystrophic and WT rat retina up to 6 months after grafting and expressed nestin,
vimentin, GFAP, and betaIII tubulin. Vision and retinal structure remained normal
in WT rats injected with hRPC and there was no evidence of tumors. A comparison
between dexamethasone-treated and untreated dystrophic rats at 3 months after
grafting revealed an unexpected reduction in the baseline visual acuity of
dexamethasone-treated animals. CONCLUSIONS: Human retinal progenitor cells appear
safe and efficacious in the preclinical models used here. TRANSLATIONAL
RELEVANCE: Human retinal progenitor cells could be deployed during early stages
of retinal degeneration or in regions of intact retina, without adverse effects
on visual function. The ability of dexamethasone to reduce baseline visual acuity
in RCS dystrophic rats has important implications for the interpretation of
preclinical and clinical cell transplant studies.
PMID- 27486558
TI - Racial and ethnic minority patients report different weight-related care
experiences than non-Hispanic Whites.
AB - Our objective was to compare patients' health care experiences, related to their
weight, across racial and ethnic groups. In Summer 2015, we distributed a written
survey with telephone follow-up to a random sample of 5400 racially/ethnically
and geographically diverse U.S. adult health plan members with overweight or
obesity. The survey assessed members' perceptions of their weight-related
healthcare experiences, including their perception of their primary care
provider, and the type of weight management services they had been offered, or
were interested in. We used multivariable multinomial logistic regression to
examine the relationship between race/ethnicity and responses to questions about
care experience. Overall, 2811 members (53%) responded to the survey and we
included 2725 with complete data in the analysis. Mean age was 52.7 years (SD
15.0), with 61.7% female and 48.3% from minority racial/ethnic groups. Mean BMI
was 37.1 kg/m(2) (SD 8.0). Most (68.2%) respondents reported having previous
discussions of weight with their provider, but interest in such counseling varied
by race/ethnicity. Non-Hispanic blacks were significantly less likely to
frequently avoid care (for fear of discussing weight/being weighed) than whites
(OR 0.49, 95% CI 0.26-0.90). Relative to whites, respondents of other
race/ethnicities were more likely to want weight-related discussions with their
providers. Race/ethnicity correlates with patients' perception of discussions of
weight in healthcare encounters. Clinicians should capitalize on opportunities to
discuss weight loss with high-risk minority patients who may desire these
conversations.
PMID- 27486559
TI - Electronic health record-based assessment of cardiovascular health: The stroke
prevention in healthcare delivery environments (SPHERE) study.
AB - < 3% of Americans have ideal cardiovascular health (CVH). The primary care
encounter provides a setting in which to conduct patient-provider discussions of
CVH. We implemented a CVH risk assessment, visualization, and decision-making
tool that automatically populates with electronic health record (EHR) data during
the encounter in order to encourage patient-centered CVH discussions among at
risk, yet under-treated, populations. We quantified five of the seven CVH
behaviors and factors that were available in The Ohio State University Wexner
Medical Center's EHR at baseline (May-July 2013) and compared values to those
ascertained at one-year (May-July 2014) among intervention (n = 109) and control
(n = 42) patients. The CVH of women in the intervention clinic improved relative
to the metrics of body mass index (16% to 21% ideal) and diabetes (62% to 68%
ideal), but not for smoking, total cholesterol, or blood pressure. Meanwhile, the
CVH of women in the control clinic either held constant or worsened slightly as
measured using those same metrics. Providers need easy-to-use tools at the point
of-care to help patients improve CVH. We demonstrated that the EHR could deliver
such a tool using an existing American Heart Association framework, and we noted
small improvements in CVH in our patient population. Future work is needed to
assess how to best harness the potential of such tools in order to have the
greatest impact on the CVH of a larger patient population.
PMID- 27486560
TI - Smokers' and e-cigarette users' perceptions of modified risk warnings for e
cigarettes.
AB - The 2009 Family Smoking Prevention and Tobacco Control Act opened the possibility
for tobacco companies to apply to market their products as having "modified" or
reduced risks. However, research on how to communicate comparative tobacco risks
and how such messages are interpreted is limited. This study aimed to
qualitatively examine perceptions of potential modified risk statements presented
as warning labels for e-cigarettes. We conducted six focus groups between 2014
and 2015 with 27 adult e-cigarette users and cigarette-only smokers who provided
comments on two versions of a modified risk warning for e-cigarettes: 1)
"WARNING: No tobacco product is safe, but this product presents substantially
lower risks to health than cigarettes" (as proposed by two companies for their
smokeless tobacco products) and 2) "WARNING: This product may be harmful to
health, but is substantially less harmful than cigarettes" (an alternative
developed by our team). Although most personally believed that e-cigarettes are
safer than cigarettes and some thought the messages were true and accurate, many
were skeptical and uncomfortable with the warnings because they did not "seem
like a warning" and because use of the phrase "substantially lower risks" could
be misleading and difficult to understand. Several thought the second warning was
stronger (e.g., more active, more specific). Modified risk messages about e
cigarettes may impact perceptions and use of the product. More research is needed
to identify the framing, wording and placement (e.g. within or in addition to a
warning) that could potentially increase population-level benefits and minimize
harms.
PMID- 27486561
TI - Testing the theory of holism: A study of family systems and adolescent health.
AB - Holism is an ancient theory that can be applied contemporarily to adolescent
health and its determinants. This theory suggests that there is value in
considering factors that influence health together as integrated wholes, in
addition to consideration of individual components. Characteristics of families
are fundamental determinants of health and provide opportunity for exploration of
this theory. In a "proof-of-concept" analysis we therefore: (1) developed a
multidimensional, composite (holistic) measure to be used to characterize family
systems; and (2) related this measure and its individual components to adolescent
health outcomes, in order to test the theory of holism. Cross-sectional analyses
of survey reports from the 2014 Canadian Health Behaviour in School-aged Children
study (weighted n = 19,333) were performed. Factor analysis was used to confirm
the psychometric properties of the holistic measure to describe a family system
(the "holistic measure"). Associations between this holistic measure, its
individual components, and various indicators of health were examined
descriptively and using binomial regression. The holistic measure (4 items, alpha
= 0.62; RMSEA = .04; SRMR = 0.01; AGFI = 0.99) included components describing
family: material wealth, meal practices, neighbourhood social capital, and social
connections. It was consistently associated with various health behaviours, and
social and emotional health outcomes. In 22/24 comparisons, this holistic measure
related to positive health outcomes more strongly than did its individual
components; for negative health outcomes this occurred in 20/24 comparisons.
Study findings suggest that it is possible to assess family systems holistically.
Such systems are strongly associated with adolescent health outcomes, and there
is etiological and theoretical value in considering family systems as integrated
wholes.
PMID- 27486562
TI - Change in settings for early-season influenza vaccination among US adults, 2012
to 2013.
AB - Vaccination in non-medical settings is recommended as a strategy to increase
access to seasonal influenza vaccine. To evaluate change in early-season
influenza vaccination setting, we analyzed data from the National Internet Flu
Survey. Bivariate comparison of respondent characteristics by location of
vaccination was assessed using chi-square tests. Multinomial logistic regression
was performed to compare the predicted probability of being vaccinated in
medical, retail, and mobile settings in 2012 vs 2013. In both 2012 and 2013,
vaccination in medical settings was more likely among elderly adults, those with
chronic conditions, and adults with a high school education or less. Adults 18-64
without a chronic condition had a lower probability of vaccination in the medical
setting, and higher probability of vaccination in a retail or mobile setting, in
2013 compared to 2012. Adults 18-64 with a chronic condition had no change in
their location of flu vaccination. Elderly adults had a lower probability of
vaccination in the medical setting, and higher probability of vaccination in a
retail setting, in 2013 compared to 2012. Non-medical settings continue to play
an increasing role in influenza vaccination of adults, particularly for adults
without a chronic condition and elderly adults. Retail and mobile settings should
continue to be viewed as important mechanisms to ensure broad access to influenza
vaccination.
PMID- 27486564
TI - Educational gradients in five Asian immigrant populations: Do country of origin,
duration and generational status moderate the education-health relationship?
AB - Education usually shows a relationship with self-rated health such that those
with highest education have the best health and those with lowest education have
the worst health. We examine these educational gradients among Asian immigrants
and whether they differ by country of origin, duration in the United States, and
generational status. Migration theories suggest that recent immigrants from
poorer countries should show a weaker relationship between education and health
than US-born Whites. Acculturation theory further suggests that differences in
gradients across country of origin should diminish for longer-term immigrants and
the US-born and that these groups should display gradients similar to US-born
Whites. We use the March Current Population Survey (2000 - 2010) to examine
educational gradients in self-rated health among recent immigrants (<= 15 years
duration), longer-term immigrants (> 15 years duration), and second generation US
born Asians from China (n = 4473), India (n = 4,307), the Philippines (n = 5746),
South Korea (n = 2760), and Japan (n = 1265). We find weak or non-significant
educational gradients among recent Asian immigrants across the five countries of
origin. There is no indication that longer-term immigrants display significant
differences across educational status. Only second generation Chinese and
Filipinos show significant differences by educational status. Overall, Asians
show an attenuated relationship between education and self-rated health compared
to US-Whites that persists over duration in the US and generational status. Our
findings show shortcomings in migration and acculturation theories to explain
these gradient patterns. Future research could use binational data or explore
psychosocial factors to identify potential suppressors of educational gradients.
PMID- 27486565
TI - Transcriptional profiling of immortalized and K-ras-transformed mouse fibroblasts
upon PKA stimulation by forskolin in low glucose availability.
AB - Forskolin (FSK) induces activation of protein kinase A (PKA). This activation
protects specifically some cancer cells from death induced by glucose starvation.
Cell effects upon FSK treatment prompted us to investigate in detail the
physiological role of PKA in the activation of pro-survival mechanisms in glucose
starvation. In this regard we performed a microarray analysis of normal NIH3T3
and transformed NIH3T3-K-ras mouse fibroblasts cultured at 1 mM glucose and daily
treated or not with 10 MUM FSK until 72 h of growth, when the samples were
collected. The microarray is deposited into Gene Expression Omnibus under Series
GSE68266. The microarray data revealed that the activation of PKA regulates the
expression of genes involved in metabolic, stress-response and pro-survival
processes, like glutamine metabolism, autophagy and unfolded protein response,
preventing cancer cell death in glucose starvation. Altogether these findings
suggest that PKA activation, by inducing a complex transcriptional program, leads
to cancer survival in nutrient stress, a typical feature of developing tumor.
These transcriptional data, identifying this important role of PKA, will be
useful to identify novel target in cancer therapy.
PMID- 27486563
TI - Smoking status and abdominal obesity among normal- and overweight/obese adults:
Population-based FINRISK study.
AB - Several studies have reported direct associations of smoking with body mass index
(BMI) and abdominal obesity. However, the interplay between them is poorly
understood. Our first aim was to investigate the interaction between smoking
status and BMI on abdominal obesity (waist circumference, WC). Our second aim was
to examine how the association of smoking status with WC varies among normal and
overweight/obese men and women. We examined 5833 participants from the National
FINRISK 2007 Study. The interactions between smoking and BMI on WC were analyzed.
Participants were categorized into eight groups according to BMI (normal weight
vs. overweight/obese) and smoking status (never smoker, ex-smoker,
occasional/light/moderate daily smoker, heavy daily smoker). The associations
between each BMI/smoking status -group and WC were analyzed by multiple
regressions, the normal-weight never smokers as the reference group. The smoking
status by BMI-interaction on WC was significant for women, but not for men. Among
the overweight/obese women, ex-smokers (beta = 2.73; 1.99, 3.46) and heavy daily
smokers (beta = 4.90; 3.35, 6.44) had the highest estimates for WC when adjusted
for age, BMI, alcohol consumption and physical activity. In comparison to never
smoking overweight/obese women, the beta-coefficients of ex-smokers and heavy
daily smokers were significantly higher. Among men and normal weight women the
beta -coefficients did not significantly differ by smoking status. An interaction
between smoking status and BMI on abdominal obesity was observed in women:
overweight/obese heavy daily smokers were particularly vulnerable for abdominal
obesity. This risk group should be targeted for cardiovascular disease
prevention.
PMID- 27486566
TI - De novo sequencing of Eucommia ulmoides flower bud transcriptomes for
identification of genes related to floral development.
AB - Eucommia ulmoides Oliver is a woody perennial dioecious species native to China
and has great economic value. However, little is known about flower bud
development in this species. In this study, the transcriptomes of female and male
flower buds were sequenced using the Illumina platform, a next-generation
sequencing technology that provides cost-effective, highly efficient
transcriptome profiling. In total, 11,558,188,080 clean reads were assembled into
75,065 unigenes with an average length of 1011 bp by de novo assembly using
Trinity software. Through similarity comparisons with known protein databases,
47,071 unigenes were annotated, 146 of which were putatively related to the
floral development of E. ulmoides. Fifteen of the 146 unigenes had significantly
different expression levels between the two samples. Additionally, 24,346 simple
sequence repeats were identified in 18,565 unigenes with 12,793 sequences
suitable for the designed primers. In total, 67,447 and 58,236 single nucleotide
polymorphisms were identified in male and female buds, respectively. This study
provides a valuable resource for further conservation genetics and functional
genomics research on E. ulmoides.
PMID- 27486567
TI - Neuroendocrine Tumors of the Large Intestine: Clinicopathological Features and
Predictive Factors of Lymph Node Metastasis.
AB - A new histological classification of neuroendocrine tumors (NETs) was established
in WHO 2010. ENET and NCCN proposed treatment algorithms for colorectal NET.
Retrospective study of NET of the large intestine (colorectal and appendiceal
NET) was performed among institutions allied with the Japanese Society for Cancer
of the Colon and Rectum, and 760 neuroendocrine tumors from 2001 to 2011 were re
assessed using WHO 2010 criteria to elucidate the clinicopathological features of
NET in the large intestine. Next, the clinicopathological relationship with lymph
node metastasis was analyzed to predict lymph node metastasis in locally resected
rectal NET. The primary site was rectum in 718/760 cases (94.5%), colon in 30/760
cases (3.9%), and appendix in 12/760 cases (1.6%). Patients were predominantly
men (61.6%) with a mean age of 58.7 years. Tumor size was <10 mm in 65.4% of
cases. Proportions of NET G1, G2, G3, and mixed adeno-neuroendocrine carcinoma
(MANEC) were 88.4, 6.3, 3.9, and 1.3%, respectively. Of the 760 tumors, 468 were
locally resected, and 292 were surgically resected with lymph node dissection.
Rectal NET showed a higher proportion of NET G1, and colonic and appendiceal NET
was more commonly G3 and MANEC. Of the 292 surgically resected cases, 233 NET G1
and G2 located in the rectum were used for the prediction of lymph node
metastasis. Lymphatic and blood vessel invasion were independent predictive
factors of lymph node metastasis. NET G2 cases showed more frequent lymph node
metastasis than that seen in NET G1 cases, but this was not an independent
predictor of lymph node metastasis. Of the 98 surgically resected cases <10 mm in
size, we found 9 cases with lymph node metastasis (9.2%). All cases were NET G1,
and eight of the nine cases were positive either for lymphatic invasion or blood
vessel invasion. Using the WHO classification, we found NET in the large
intestine showed a tumor-site-dependent variety of histological and
clinicopathological features. Risk of lymph node metastasis in rectal NET was
confirmed even in lesions smaller than 10 mm. Concordant assessment of vascular
invasion will be required to estimate lymph node metastasis in small lesions.
PMID- 27486568
TI - Effectiveness of sulphonylureas in the therapy of diabetes mellitus type 2
patients: an observational cohort study.
AB - BACKGROUND: We compared all-cause mortality, major macrovascular events (MACE)
and diabetes-related hospitalizations in T2DM-incident patients newly treated
with metformin (MET) versus sulphonylureas (SU) monotherapy and in T2DM-prevalent
patients newly treated with MET+SU versus MET+DPP4-inhibitor combination therapy.
METHODS: We analysed anonymized data obtained from a German health fund. Patients
were included when they had started MET versus SU therapy or MET+SU versus
MET+DPP4 therapy between 01/07/2010 and 31/12/2011. Observation started with the
first MET/SU prescription or the first prescription of the second agent of a
MET+SU/MET+DPP4 combination therapy. Follow-up time lasted until the end of data
availability (a minimum of 12 months), death or therapy discontinuation. RESULTS:
In total, 434,291 T2DM-prevalent and 35,661 T2DM-incident patients were
identified. Of the identified T2DM-incident patients, 904/7,874 started SU/MET
monotherapy, respectively, with a mean age of 70.1/61.4 years (54.6/50.3 %
female; Charlson Comorbidity Index (CCI) 1.4/2.2; 933/7,350 observed SU/MET
patient years). 4,157/1,793 SU+MET/DPP4+MET therapy starters had a mean age of
68.1/62.2 years (53.4/50.8 % female; CCI 2.8/2.6; 4,556/1,752 observed SU+MET/
DPP4+MET patient years). In a propensity score matched (PSM) comparison, the HRs
(95 % CIs) associated with SU monotherapy compared to MET monotherapy exposure
were 1.4 (0.9-2.3) for mortality, 1.4 (0.9-2.2) for MACE, 4.1 (1.5-10.9) for T2DM
hospitalizations and 1.6 (1.2-2.3) for composite event risk. In a multivariable
Cox regression model, SU monotherapy was associated with higher mortality (aHR
2.0; 1.5-2.6), higher MACE (aHR 1.3; 1.0-1.7) and higher T2DM hospitalizations
(aHR 2.8; 1.8-4.4), which corresponded with a higher composite event risk (aHR
1.8; 1.5-2.1). No significant differences in event rates were observed in the PSM
comparison between DPP4+MET/SU+MET combination therapy starters and in the
multivariable Cox regression analysis. CONCLUSIONS: Our results show that SU
monotherapy may be associated with increased mortality, MACE and T2DM
hospitalizations, compared to MET monotherapy. When considering SU therapy, the
associated cardiovascular risk should also be taken into account.
PMID- 27486569
TI - Vasectomy and prostate cancer risk: a historical synopsis of undulating false
causality.
AB - The potential influence of vasectomy being a risk factor for the development of
prostate cancer is not a new concept, with more than 30 publications addressing
the topic. Given the global frequency of vasectomy and the prevalence of prostate
cancer, this subject justifiably deserves scrutiny. Several articles have claimed
that vasectomy puts men at risk for future development of prostate cancer. We
explore articles that have shown the contrary (no link), explore the studies'
strengths and weaknesses, describe possible prostate cancer pathophysiologic
mechanisms, and apply Bradford Hill criteria to help discern correlation with
causation. The risk and interest of association of prostate cancer with vasectomy
has waxed and waned over the last three decades. Based on our review, vasectomy
remains a safe form of sterilization and does not increase prostate cancer risk.
PMID- 27486570
TI - Prevalence, psychological impact, and risk factors of erectile dysfunction in
patients with Peyronie's disease: a retrospective analysis of 309 cases.
AB - Peyronie's disease (PD) is a chronic inflammatory disease involving the tunica
albuginea of the penis. Erectile dysfunction (ED) is a possible invalidating
symptom of PD. The aim of this study was to evaluate the prevalence,
psychological impact, and risk factors of ED in patients with PD. The study was
conducted by carrying out a retrospective analysis of the clinical records of 309
patients with PD who visited our andrology clinic. All patients underwent the
following tests: body mass index, common blood tests and hormone assays,
questionnaire for erectile function assessment, dynamic penile color Doppler
ultrasonography, imaging of the penis at maximum erection with photographic poses
according to Kelami, psychosexual impact evaluation with PD Questionnaire
(symptom bother score), evaluation of depression symptoms with the Patient Health
Questionnaire-9, and evaluation of the intensity of penile pain with the pain
intensity numeric rating scale. ED was observed in 37.5% of the cases. We divided
the cases into two groups: group A (PD + ED), 116 cases, and group B (PD without
ED), 193 cases. After multivariate analysis, we concluded that the following
comorbidities are independent risk factors for ED: dyslipidemia, obesity, chronic
prostatitis, benign prostatic hyperplasia, and autoimmune diseases. A depressive
disorder was observed in 62.4%, and it was more frequent in patients with PD + ED
(91.37% versus 45.07% group B). Sexual bother was greater in group A compared
with group B (9.7 versus 7.6). Intensities of depressive symptoms and sexual
bother were significantly higher compared with cases with no curvature when the
bend angle was >=30 degrees . Our study confirms that an integrated psychological
support with medical treatment is needed in patients with PD.
PMID- 27486572
TI - Spatial-Temporal Analysis of Air Pollution, Climate Change, and Total Mortality
in 120 Cities of China, 2012-2013.
AB - China has had a rapid increase in its economy over the past three decades.
However, the economic boom came at a certain cost of depleting air quality. In
the study, we aimed to examine the burden of air pollution and its association
with climatic factors and health outcomes using data from Chinese national and
city-level air quality and public health surveillance systems. City-level daily
air pollution index (API, a sum weighted index of SO2, NO2, PM10, CO, and Ozone)
in 120 cities in 2012 and 2013, and its association with climate factors were
analyzed using multiple linear regression analysis, spatial autocorrelation
analysis, and panel fixed models. City-level ecological association between
annual average API and total mortality were examined using univariate and partial
correlation analysis. Sensitivity analysis was conducted by taking the
consideration of time-lag effect between exposures and outcomes. The results show
that among the 120 cities, annual average API significantly increased from 2012
to 2013 (65.05 vs. 75.99, p < 0.0001). The highest average API was in winter, and
the lowest in summer. A significantly spatial clustering of elevated API was
observed, with the highest API in northwest China in 2012 and with the highest in
east China in 2013. In 2012, 5 (4%) of the 120 cities had >=60 days with API >100
(defined as "slightly polluted"), however, it increased to 21 cities (18%) that
experienced API >100 for >=60 days in 2013. Furthermore, 16 cities (13%) in 2012
and 35 (29%) in 2013 experienced a maximum API >300 (defined as "severely
polluted"). API was negatively and significantly correlated with heat index,
precipitation, and sunshine hours, but positively with air pressure. Cities with
higher API concentrations had significantly higher total mortality rates than
those with lower API. About a 4-7% of the variation in total mortality could be
explained by the difference in API across the nation. In conclusion, the study
highlights an increased trend of air pollution from 2012 to 2013 in China. The
magnitude of air pollution varied by seasons and regions and correlated with
climatic factors and total mortality across the country.
PMID- 27486571
TI - Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a
Retrospective Cohort Study.
AB - INTRODUCTION: Acute kidney injury (AKI) affects ~30% of hospitalized neonates.
Critical to advancing our understanding of neonatal AKI is collaborative research
among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC)
is an international, multidisciplinary group dedicated to investigating neonatal
AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology
in Neonates) was designed to describe the epidemiology of neonatal AKI, validate
the definition of neonatal AKI, identify primary risk factors for neonatal AKI,
and investigate the contribution of fluid management to AKI events and short-term
outcomes. METHODS AND ANALYSIS: The NKC was established with at least one
pediatric nephrologist and neonatologist from 24 institutions in 4 countries
(USA, Canada, Australia, and India). A Steering Committee and four subcommittees
were created. The database subcommittee oversaw the development of the web-based
database (MediData RaveTM) that captured all NICU admissions from 1/1/14 to
3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with
a low likelihood of AKI. Data collection included: (1) baseline demographic
information; (2) daily physiologic parameters and care received during the first
week of life; (3) weekly "snapshots"; (4) discharge information including growth
parameters, final diagnoses, discharge medications, and need for renal
replacement therapy; and (5) all serum creatinine values. ETHICS AND
DISSEMINATION: AWAKEN was proposed as human subjects research. The study design
allowed for a waiver of informed consent/parental permission. NKC investigators
will disseminate data through peer-reviewed publications and educational
conferences. DISCUSSION: The purpose of this publication is to describe the
formation of the NKC, the establishment of the AWAKEN cohort and database, future
directions, and a few "lessons learned." The AWAKEN database includes ~325 unique
variables and >4 million discrete data points. AWAKEN will be the largest, most
inclusive neonatal AKI study to date. In addition to validating the neonatal AKI
definition and identifying risk factors for AKI, this study will uncover
variations in practice patterns related to fluid provision, renal function
monitoring, and involvement of pediatric nephrologists during hospitalization.
The AWAKEN study will position the NKC to achieve the long-term goal of improving
the lives, health, and well-being of newborns at risk for kidney disease.
PMID- 27486574
TI - Using Virtual Reality in the Inference-Based Treatment of Compulsive Hoarding.
AB - The present study evaluated the efficacy of adding a virtual reality (VR)
component to the treatment of compulsive hoarding (CH), following inference-based
therapy (IBT). Participants were randomly assigned to either an experimental or a
control condition. Seven participants received the experimental and seven
received the control condition. Five sessions of 1 h were administered weekly. A
significant difference indicated that the level of clutter in the bedroom tended
to diminish more in the experimental group as compared to the control group
F(2,24) = 2.28, p = 0.10. In addition, the results demonstrated that both groups
were immersed and present in the environment. The results on posttreatment
measures of CH (Saving Inventory revised, Saving Cognition Inventory and Clutter
Image Rating scale) demonstrate the efficacy of IBT in terms of symptom
reduction. Overall, these results suggest that the creation of a virtual
environment may be effective in the treatment of CH by helping the compulsive
hoarders take action over their clutter.
PMID- 27486573
TI - Chemical Pesticides and Human Health: The Urgent Need for a New Concept in
Agriculture.
AB - The industrialization of the agricultural sector has increased the chemical
burden on natural ecosystems. Pesticides are agrochemicals used in agricultural
lands, public health programs, and urban green areas in order to protect plants
and humans from various diseases. However, due to their known ability to cause a
large number of negative health and environmental effects, their side effects can
be an important environmental health risk factor. The urgent need for a more
sustainable and ecological approach has produced many innovative ideas, among
them agriculture reforms and food production implementing sustainable practice
evolving to food sovereignty. It is more obvious than ever that the society needs
the implementation of a new agricultural concept regarding food production, which
is safer for man and the environment, and to this end, steps such as the
declaration of Nyeleni have been taken.
PMID- 27486575
TI - Compensating for Electrode Polarization in Dielectric Spectroscopy Studies of
Colloidal Suspensions: Theoretical Assessment of Existing Methods.
AB - Dielectric spectroscopy can be used to determine the dipole moment of colloidal
particles from which important interfacial electrokinetic properties, for
instance their zeta potential, can be deduced. Unfortunately, dielectric
spectroscopy measurements are hampered by electrode polarization (EP). In this
article, we review several procedures to compensate for this effect. First EP in
electrolyte solutions is described: the complex conductivity is derived as
function of frequency, for two cell geometries (planar and cylindrical) with
blocking electrodes. The corresponding equivalent circuit for the electrolyte
solution is given for each geometry. This equivalent circuit model is extended to
suspensions. The complex conductivity of a suspension, in the presence of EP, is
then calculated from the impedance. Different methods for compensating for EP are
critically assessed, with the help of the theoretical findings. Their limit of
validity is given in terms of characteristic frequencies. We can identify with
one of these frequencies the frequency range within which data uncorrected for EP
may be used to assess the dipole moment of colloidal particles. In order to
extract this dipole moment from the measured data, two methods are reviewed: one
is based on the use of existing models for the complex conductivity of
suspensions, the other is the logarithmic derivative method. An extension to
multiple relaxations of the logarithmic derivative method is proposed.
PMID- 27486576
TI - Quantifying Dynamic Changes in Plantar Pressure Gradient in Diabetics with
Peripheral Neuropathy.
AB - Diabetic foot ulcers remain one of the most serious complications of diabetes.
Peak plantar pressure (PPP) and peak pressure gradient (PPG) during walking have
been shown to be associated with the development of diabetic foot ulcers. To gain
further insight into the mechanical etiology of diabetic foot ulcers, examination
of the pressure gradient angle (PGA) has been recently proposed. The PGA
quantifies directional variation or orientation of the pressure gradient during
walking and provides a measure of whether pressure gradient patterns are
concentrated or dispersed along the plantar surface. We hypothesized that
diabetics at risk of foot ulceration would have smaller PGA in key plantar
regions, suggesting less movement of the pressure gradient over time. A total of
27 participants were studied, including 19 diabetics with peripheral neuropathy
and 8 non-diabetic control subjects. A foot pressure measurement system was used
to measure plantar pressures during walking. PPP, PPG, and PGA were calculated
for four foot regions - first toe (T1), first metatarsal head (M1), second
metatarsal head (M2), and heel (HL). Consistent with prior studies, PPP and PPG
were significantly larger in the diabetic group compared with non-diabetic
controls in the T1 and M1 regions, but not M2 or HL. For example, PPP was 165% (P
= 0.02) and PPG was 214% (P < 0.001) larger in T1. PGA was found to be
significantly smaller in the diabetic group in T1 (46%, P = 0.04), suggesting a
more concentrated pressure gradient pattern under the toe. The proposed PGA may
improve our understanding of the role of pressure gradient on the risk of
diabetic foot ulcers.
PMID- 27486579
TI - Editorial: Metabolome Informatics and Statistics: Current State and Emerging
Trends.
PMID- 27486577
TI - Expression of S-adenosylmethionine Hydrolase in Tissues Synthesizing Secondary
Cell Walls Alters Specific Methylated Cell Wall Fractions and Improves Biomass
Digestibility.
AB - Plant biomass is a large source of fermentable sugars for the synthesis of
bioproducts using engineered microbes. These sugars are stored as cell wall
polymers, mainly cellulose and hemicellulose, and are embedded with lignin, which
makes their enzymatic hydrolysis challenging. One of the strategies to reduce
cell wall recalcitrance is the modification of lignin content and composition.
Lignin is a phenolic polymer of methylated aromatic alcohols and its synthesis in
tissues developing secondary cell walls is a significant sink for the consumption
of the methyl donor S-adenosylmethionine (AdoMet). In this study, we demonstrate
in Arabidopsis stems that targeted expression of AdoMet hydrolase (AdoMetase,
E.C. 3.3.1.2) in secondary cell wall synthesizing tissues reduces the AdoMet pool
and impacts lignin content and composition. In particular, both NMR analysis and
pyrolysis gas chromatography mass spectrometry of lignin in engineered biomass
showed relative enrichment of non-methylated p-hydroxycinnamyl (H) units and a
reduction of dimethylated syringyl (S) units. This indicates a lower degree of
methylation compared to that in wild-type lignin. Quantification of cell wall
bound hydroxycinnamates revealed a reduction of ferulate in AdoMetase transgenic
lines. Biomass from transgenic lines, in contrast to that in control plants,
exhibits an enrichment of glucose content and a reduction in the degree of
hemicellulose glucuronoxylan methylation. We also show that these modifications
resulted in a reduction of cell wall recalcitrance, because sugar yield generated
by enzymatic biomass saccharification was greater than that of wild-type plants.
Considering that transgenic plants show no important diminution of biomass
yields, and that heterologous expression of AdoMetase protein can be
spatiotemporally optimized, this novel approach provides a valuable option for
the improvement of lignocellulosic biomass feedstock.
PMID- 27486578
TI - How Biomaterials Can Influence Various Cell Types in the Repair and Regeneration
of the Heart after Myocardial Infarction.
AB - The healthy heart comprises many different cell types that work together to
preserve optimal function. However, in a diseased heart the function of one or
more cell types is compromised which can lead to many adverse events, one of
which is myocardial infarction (MI). Immediately after MI, the cardiac
environment is characterized by excessive cardiomyocyte death and inflammatory
signals leading to the recruitment of macrophages to clear the debris.
Proliferating fibroblasts then invade, and a collagenous scar is formed to
prevent rupture. Better functional restoration of the heart is not achieved due
to the limited regenerative capacity of cardiac tissue. To address this,
biomaterial therapy is being investigated as an approach to improve regeneration
in the infarcted heart, as they can possess the potential to control cell
function in the infarct environment and limit the adverse compensatory changes
that occur post-MI. Over the past decade, there has been considerable research
into the development of biomaterials for cardiac regeneration post-MI; and
various effects have been observed on different cell types depending on the
biomaterial that is applied. Biomaterial treatment has been shown to enhance
survival, improve function, promote proliferation, and guide the mobilization and
recruitment of different cells in the post-MI heart. This review will provide a
summary on the biomaterials developed to enhance cardiac regeneration and
remodeling post-MI with a focus on how they control macrophages, cardiomyocytes,
fibroblasts, and endothelial cells. A better understanding of how a biomaterial
interacts with the different cell types in the heart may lead to the development
of a more optimized biomaterial therapy for cardiac regeneration.
PMID- 27486581
TI - Next Step in Cost Containment of Public Hospital Economy Could Be Merging of
Anesthesia and Surgery Budgets.
PMID- 27486580
TI - Achiasmy: Male Fruit Flies Are Not Ready to Mix.
AB - Maintenance of the chromosomal copy number over generations and recombination
between homologous chromosomes are hallmarks of meiotic cell division. This
genetic exchange that take place during gamete formation leads to genetic
diversity, the main driving force behind natural selection. Formation of
chiasmata, the physical link between homologous chromosomes during meiosis, is a
requisite for recombination. In addition, chiasmata also aid in proper
segregation of homologous chromosomes and has a major impact on reproductive
fitness. Given these facts it is intriguing that many insect species have forgone
the need for genetic exchange between homologous chromosomes during meiosis.
Geneticists for several decades knew that meiotic crossover and recombination is
absent in Drosophila males and some female lepidopterans, a condition termed
achiasmy. However, a good understanding of the mechanisms that cause achiasmy and
the evolutionary benefits of achiasmy is currently lacking. In this article we
will discuss possible genetic and molecular basis of achiasmy in male Drosophila.
PMID- 27486582
TI - Conjugative DNA Transfer Is Enhanced by Plasmid R1 Partitioning Proteins.
AB - Bacterial conjugation is a form of type IV secretion used to transport protein
and DNA directly to recipient bacteria. The process is cell contact-dependent,
yet the mechanisms enabling extracellular events to trigger plasmid transfer to
begin inside the cell remain obscure. In this study of plasmid R1 we investigated
the role of plasmid proteins in the initiation of gene transfer. We find that
TraI, the central regulator of conjugative DNA processing, interacts physically,
and functionally with the plasmid partitioning proteins ParM and ParR. These
interactions stimulate TraI catalyzed relaxation of plasmid DNA in vivo and in
vitro and increase ParM ATPase activity. ParM also binds the coupling protein
TraD and VirB4-like channel ATPase TraC. Together, these protein-protein
interactions probably act to co-localize the transfer components intracellularly
and promote assembly of the conjugation machinery. Importantly these data also
indicate that the continued association of ParM and ParR at the conjugative pore
is necessary for plasmid transfer to start efficiently. Moreover, the conjugative
pilus and underlying secretion machinery assembled in the absence of Par proteins
mediate poor biofilm formation and are completely dysfunctional for pilus
specific R17 bacteriophage uptake. Thus, functional integration of Par components
at the interface of relaxosome, coupling protein, and channel ATPases appears
important for an optimal conformation and effective activation of the transfer
machinery. We conclude that low copy plasmid R1 has evolved an active segregation
system that optimizes both its vertical and lateral modes of dissemination.
PMID- 27486583
TI - Age-Dependent Effects of Haptoglobin Deletion in Neurobehavioral and Anatomical
Outcomes Following Traumatic Brain Injury.
AB - Cerebral hemorrhages are common features of traumatic brain injury (TBI) and
their presence is associated with chronic disabilities. Recent clinical and
experimental evidence suggests that haptoglobin (Hp), an endogenous hemoglobin
binding protein most abundant in blood plasma, is involved in the intrinsic
molecular defensive mechanism, though its role in TBI is poorly understood. The
aim of this study was to investigate the effects of Hp deletion on the anatomical
and behavioral outcomes in the controlled cortical impact model using wildtype
(WT) C57BL/6 mice and genetically modified mice lacking the Hp gene (Hp(-/-)) in
two age cohorts [2-4 mo-old (young adult) and 7-8 mo-old (older adult)]. The data
obtained suggest age-dependent significant effects on behavioral and anatomical
TBI outcomes and recovery from injury. Moreover, in the adult cohort,
neurological deficits in Hp(-/-) mice at 24 h were significantly improved
compared to WT, whereas there were no significant differences in brain pathology
between these genotypes. In contrast, in the older adult cohort, Hp(-/-) mice had
significantly larger lesion volumes compared to WT, but neurological deficits
were not significantly different. Immunohistochemistry for ionized calcium
binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)
revealed significant differences in microglial and astrocytic reactivity between
Hp(-/-) and WT in selected brain regions of the adult but not the older adult
aged cohort. In conclusion, the data obtained in the study provide clarification
on the age-dependent aspects of the intrinsic defensive mechanisms involving Hp
that might be involved in complex pathways differentially affecting acute brain
trauma outcomes.
PMID- 27486585
TI - Another milestone: Stem Cell Investigation is indexed in PubMed/PMC.
PMID- 27486584
TI - Therapeutic Management of Feline Chronic Gingivostomatitis: A Systematic Review
of the Literature.
AB - Feline chronic gingivostomatitis (FCGS) is a disease characterized by protracted
and potentially debilitating oral inflammation in cats, the etiology of which is
currently unknown. The purpose of this review is to apply an evidence-based
medicine approach to systematically review and critically evaluate the scientific
literature reporting the outcome of medical and surgical management of FCGS.
Those articles meeting inclusion criteria were reviewed and assigned an
"Experimental Design Grade" (EDG) and an "Evidence Grade" (EG) in order to score
relative strength of study design and produced data. Studies were evaluated and
compared, especially highlighting the treatments, the outcomes, and the
therapeutic success rates. This review found a lack of consistency between
articles' data, rendering direct comparison of results unreliable. The field of
FCGS research, and ultimately patient care, would benefit from standardizing
studies by adopting use of a consistent semi-quantitative scoring system and
extending follow-up duration. Future researchers should commit to large
prospective studies that compare existing treatments and demonstrate the promise
of new treatments.
PMID- 27486586
TI - Inflammation-induced emergency megakaryopoiesis: inflammation paves the way for
platelets.
PMID- 27486587
TI - A rare case of the upper extremity diffuse large B-cell lymphoma mimicking soft
tissue sarcoma in an elderly patient.
AB - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin
lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions
originating from soft tissues of the upper extremities are extremely rare and may
mimic other malignancies like sarcoma. We present a case of an elderly patient
with right upper extremity (RUE) mass which was proven to be DLBCL instead of
sarcoma. We emphasize the increasing need for investigating new therapeutic
options for patients of extreme age and/or with underlying heart disease.
PMID- 27486588
TI - Treatment of symptomatic epidermolysis bullosa simplex with botulinum toxin in a
pediatric patient.
PMID- 27486589
TI - Romidepsin-induced neutrophilic urticaria.
PMID- 27486590
TI - Immune-related sarcoidosis observed in combination ipilimumab and nivolumab
therapy.
PMID- 27486591
TI - Systemic methotrexate for prurigo nodularis and keratoacanthomas in actinically
damaged skin.
PMID- 27486592
TI - Bowel-associated dermatosis-arthritis syndrome (BADAS) in a pediatric patient.
PMID- 27486593
TI - Purpuric and cream-colored plaques in an immunocompromised person: A case of
disseminated trichosporonosis.
PMID- 27486594
TI - Exuberant inflammatory reaction to occlusion of topical 5-fluorouracil (FU) under
a continuous positive airway pressure (CPAP) mask: A warning to dermatologists
and patients.
PMID- 27486595
TI - A silicon nitride ISFET based immunosensor for Ag85B detection of tuberculosis.
AB - A silicon nitride Ion Sensitive Field Effect Transistor (ISFET) based
immunosensor was developed as a low-cost and label-free electrical detection for
the detection of antigen 85 complex B (Ag85B). The sensing membrane of the ISFET
was modified with 3-aminopropyltriethoxysilane (APTES) followed by glutaraldehyde
(GA), yielding an aldehyde-terminated surface. This group is available for
immobilization of a monoclonal antibody against a recombinant Ag85B protein (anti
Ag85B antibody). The optimal concentration for anti-Ag85B antibody immobilization
onto the modified ISFET was 100 MUg ml-1. This optimal condition provided the
maximal binding capability and minimal non-specific background signal. The
binding event between the recombinant Ag85B antigen and anti-Ag85B antibody on
the ISFET surface is presented by monitoring the gate potential change at a
constant drain current. The dose response for the recombinant Ag85B protein
showed a linear response between 0.12 and 1 MUg ml-1 without significant
interference from other recombinant proteins. The analytical imprecision (CV%)
and accuracy of this Ag85B protein biosensor were 9.73-10.99% and 95.29%,
respectively. In addition, an irrelevant antibody and other recombinant proteins
were employed as a negative control to demonstrate the non-specific interaction
of the antigen and antibody. The success of this immunosensor system for Ag85B
protein detection facilitates the construction of a promising device which can
shorten the turnaround time for the diagnosis of tuberculosis compared to a
standard culture method. Furthermore, this device could also be applied for real
time growth monitoring of Mycobacterium tuberculosis in a mycobacterial culture
system.
PMID- 27486596
TI - Dyneon THV, a fluorinated thermoplastic as a novel material for microchip
capillary electrophoresis.
AB - In this work, we have investigated Dyneon THV, a fluorinated material, as a new
material to afford electrokinetic separations in microfluidic devices. To
overcome protein adsorption, two poly(ethylene oxide) (PEO)-based coatings have
been investigated: Pluronic F127 and PEO stearate 40. The best results were
obtained with the PEO stearate 40 coating which allowed decreasing the surface
contact angle from 91 +/- 3 to 76 degrees +/- 3. With this surface treatment, a
66% reduction of the electroosmotic mobility at pH 8.0 and a marked suppression
of protein adsorption were observed compared to a native Dyneon THV microchip.
Finally, a separation of fluorescently labeled proteins (bovine serum albumin and
trypsin inhibitor), well-known for their strong tendency to adsorb on hydrophobic
surfaces, was successfully achieved in an HEPES buffer with a PEO stearate 40
treated microchip by capillary zone electrophoresis. Furthermore, we demonstrated
the possibility to perform non-aqueous capillary electrophoresis analysis of
hydrophobic dyes using various solvents in untreated microchips. The overall
results demonstrated not only the suitability of the Dyneon THV microchip for
electrokinetic separations, but also its versatility allowing different
separation modes to be implemented with the same microchip material.
PMID- 27486597
TI - Macro-to-micro interfacing to microfluidic channels using 3D-printed templates:
application to time-resolved secretion sampling of endocrine tissue.
AB - Employing 3D-printed templates for macro-to-micro interfacing, a passively
operated polydimethysiloxane (PDMS) microfluidic device was designed for time
resolved secretion sampling from primary murine islets and epidiymal white
adipose tissue explants. Interfacing in similar devices is typically accomplished
through manually punched or drilled fluidic reservoirs. We previously introduced
the concept of using hand fabricated polymer inserts to template cell culture and
sampling reservoirs into PDMS devices, allowing rapid stimulation and sampling of
endocrine tissue. However, fabrication of the fluidic reservoirs was time
consuming, tedious, and was prone to errors during device curing. Here, we have
implemented computer-aided design and 3D printing to circumvent these fabrication
obstacles. In addition to rapid prototyping and design iteration advantages, the
ability to match these 3D-printed interface templates with channel patterns is
highly beneficial. By digitizing the template fabrication process, more robust
components can be produced with reduced fabrication variability. Herein, 3D
printed templates were used for sculpting millimetre-scale reservoirs into the
above-channel, bulk PDMS in passively-operated, eight-channel devices designed
for time-resolved secretion sampling of murine tissue. Devices were proven
functional by temporally assaying glucose-stimulated insulin secretion from <10
pancreatic islets and glycerol secretion from 2 mm adipose tissue explants,
suggesting that 3D-printed interface templates could be applicable to a variety
of cells and tissue types. More generally, this work validates desktop 3D
printers as versatile interfacing tools in microfluidic laboratories.
PMID- 27486598
TI - Kirsten Jackson: Aussie equine vet shares her passion for welfare.
PMID- 27486599
TI - Trust and transparency in the veterinary profession.
PMID- 27486601
TI - One of your SIGs is under threat.
PMID- 27486600
TI - Looking like leaders.
PMID- 27486602
TI - Red kite feeding at Rhayader.
PMID- 27486603
TI - International Veterinary Epilepsy Task Force consensus reports.
PMID- 27486604
TI - Employment and remuneration trends in 2016.
PMID- 27486605
TI - New koala chlamydia vaccine trialed.
PMID- 27486606
TI - Fleams added to AVA's historical collection.
PMID- 27486607
TI - Leadership qualities.
PMID- 27486608
TI - Australia Day Honours 2016.
PMID- 27486609
TI - Highlights of our media program.
PMID- 27486610
TI - Distinguished academic welcomed to senior UQ veterinary science role.
PMID- 27486611
TI - Stress and non-communicable disease: a multi-pronged approach to building
healthier coping skills.
PMID- 27486612
TI - Conceptual review article.
PMID- 27486613
TI - What qualitative research has taught us about occupational stress.
AB - While many reviews of job stress and the stressor-strain relationship have been
conducted, such reviews typically focus exclusively on quantitative data. In the
current paper, we review qualitative studies on occupational stress that met two
criteria: (1) the studies employed qualitative methods; (2) the stressors,
strains and/or coping strategies were grouped into identifiable, higher-order
categories. Results indicated that the nature of the stressors experienced varied
by (a) occupation, (b) country, (c) seniority and (d) gender. The review further
revealed that organizational constraints, work overload and interpersonal
conflict were relatively universal stressors. Anger and annoyance were the most
frequently reported psychological strains in the United States and the United
Kingdom, while Chinese workers exhibited tension and anxiety and Indian workers
exhibited acceptance. Coping strategies also varied by gender, occupation and
country. Research on gender differences suggested that, compared to men, women
tended to report more interpersonal stressors. Differences in the ways in which
the two types of methodologies are applied, as well as their relative strengths
and weaknesses, underline the value of qualitative approaches to the study of
occupational stress, especially when used in conjunction with quantitative
methods in mixed-methods studies.
PMID- 27486614
TI - Predicting employees' well-being using work-family conflict and job strain
models.
AB - The present study examined the effects of two models of work-family conflict
(WFC) and job-strain on the job-related and context-free well-being of employees.
The participants of the study consisted of Iranian employees from a variety of
organizations. The effects of three dimensions of the job-strain model and six
forms of WFC on affective well-being were assessed. The results of hierarchical
multiple regression analysis revealed that the number of working hours, strain
based work interfering with family life (WIF) along with job characteristic
variables (i.e. supervisory support, job demands and job control) all make a
significant contribution to the prediction of job-related well-being. On the
other hand, strain-based WIF and family interfering with work (FIW) significantly
predicted context-free well-being. Implications are drawn and recommendations
made regarding future research and interventions in the workplace.
PMID- 27486615
TI - Coping with coping strategies: how distributed teams and their members deal with
the stress of distance, time zones and culture.
AB - The changing world of work is increasing demands on workers through greater need
for flexibility in global collaboration. This multiple-case study uses a
qualitative research approach to study context-specific job stressors and coping
in ten geographically distributed work teams. Results demonstrate the complex and
dynamic nature of the stress-coping process and how coping strategies, adapted to
manage stress-evoking uncertainty and ambiguity in distributed work, created
secondary sources of psychological strain to individuals. The main strategies for
managing the uncertainty and ambiguity in the studied teams were extensive
emailing, travelling to face-to-face meetings and extending workdays to
collaborate simultaneously across time zones. Continuously used, these coping
strategies created work overload and strain. Experienced workers, who had good
self-management skills, succeeded in coping with these secondary sources of
strain by prioritizing and setting clear limits for workload. Less-experienced
workers were overloaded and needed more social support from their leaders and
teammates. The study proposes that distributed team members rely heavily on
individual coping resources, because spatial and temporal distance hinders or
even precludes the mobilization of social resources related to emotional,
instrumental and informational social support.
PMID- 27486616
TI - Linking household income and work-family conflict: a moderated mediation study.
AB - Research on the work-family interface has not often explored the role of
structural characteristics such as income in the associations among work
stressors, work-family conflict and family stressors. The goal of this study was
to examine household income as a moderator of the relations among these
variables. Results from a nationally (US) representative sample of 1472 employed
individuals who were married with children indicate that the relations between
work-to-family interference and family strain were stronger for individuals with
lower household incomes than for those with higher household incomes.
Furthermore, family strain was more strongly associated with family-to-work
interference for individuals in low-income households. Household income did not
moderate other relations examined in the study. Potential explanations for these
moderating effects are discussed, along with their implications for the
generalizability of findings in the work-family literature across contexts.
PMID- 27486617
TI - Authors' Response.
PMID- 27486618
TI - Social capital and psychological distress of elderly in Japanese rural
communities.
AB - The growing recognition of the social determinants of health has stimulated
research on social capital and mental health. We explored new empirical evidence
regarding whether social capital was a determinant of psychological distress.
Baseline surveys examining psychological distress were conducted in two towns in
2006-2007 (participation rates for those aged 20 or over were 27.6 per cent, 6.1
per cent). We also conducted follow-up surveys in 2008 to capture the social
capital measured by trust. By linking these data and excluding the missing data,
141 males and 234 females remained as the subjects of our study. Results showed
that the odds ratios of psychological distress was higher in groups with low
social capital measured by trust (odds ratio 2.17; 95 per cent CI, 1.40-3.36),
than those in groups with high social capital. Further, we examined the
interaction effect of social capital and social support. The odds ratios of
psychological distress was higher in groups with some social support/lower trust
(odds ratio 2.21; 95 per cent CI, 1.36-3.58) or no social support/lower trust
(odds ratio 2.07; 95 per cent CI, 1.06-4.05), than those in groups with some
social support/higher trust. These findings reinforce the hypothesized discussion
regarding pathways from social capital to psychological distress via supportive
relationships.
PMID- 27486619
TI - Immobilization stress responses in adult rats exposed in utero to immobilization.
AB - The present study investigated the influence of immobilization prenatal stress on
adult male rats, with the same postnatal stress, on the immune parameters and its
relation with plasma corticosterone (COR) and glucose levels. To study the
immunity parameters, profiles of the leucocytes, size of spleen and number of the
mononuclear cells of this organ were determined. Basal levels of COR and glucose
were higher in prenatally stressed animals. When the adult animals were exposed
to immobilization stress, COR increased but the increase was less than that for
the control group, and glucose was equal in both groups. Although postnatal acute
stress decreased the number of leucocytes and lymphocytes and increased the
number of neutrophils, the effect was lower in prenatally stressed animals; for
that reason, the ratio neutrophil/lymphocyte increased less. The number of
mononuclear cells were higher in the spleen of prenatally stressed animals. This
effect was probably due to retention of blood lymphocytes in the spleen. There
seemed to be an alteration in the redistribution of leucocytes, both in basal
conditions and under postnatal stress. The alteration of the immunological
function may be partly due to an alteration in the functionality of the
hypothalamic-pituitary-adrenal axis, which was hyperactive in basal conditions
but appeared to suffer habituation to the same stress.
PMID- 27486620
TI - Cortisol variability and self-reports in the measurement of work-related stress.
AB - We examined whether a high cortisol awakening response (CAR) and low cortisol
decline over the day (CDD) are related to self-reported work stress and well
being, and whether there are gender differences in these relationships. Three
hundred eighty-three working men and women responded to a survey measuring job
stress factors, mastery at work, symptoms and well-being. Salivary cortisol was
sampled at awakening, after 45 min and at 21:00, from which the variables CAR and
CDD were defined. A high CAR was associated with lower perceived job control and
work mastery, and poorer well-being. Low CDD was associated only with higher job
demands, but the self-report scores showed a number of interactions between
cortisol group and gender. Among women, those showing a low CDD, compared with
those with a higher CDD, had more favourable scores on a number of job stress
factors and symptom load. In contrast, among men, a similar comparison showed
those with low CDD to have poorer scores on job stress factors and symptom load.
We conclude that individuals displaying high CAR or low CDD differ from those not
displaying these cortisol profiles in self-report of work stress and well-being,
and that gender differences appear in these relationships.
PMID- 27486621
TI - Lecturing to 200 students and its effects on cytokine concentration and salivary
markers of adrenal activation.
AB - Stress not only activates the SAM system and the hypothalamic-pituitary-adrenal
axes, but also the immune system. The aims of this study are to assess the
physiological variations in saliva (cytokines, cortisol and alpha-amylase) and
perceived stress in professors when they had to lecture to 200 students. A total
of eight unstimulated saliva samples were collected from nine professors: four on
a working day that included the lecture and four controls on a working day
without a lecture. The professors also rated subjective stress on a seven-point
scale 5 min before the lecture, immediately after the lecture and at the same
times on the control day. The lecture elicited substantial increases in
subjective stress ratings, with the values on the lecture day significantly
higher than those on the control day. Lecturing resulted in significant increases
in Tumor Necrosis Factor (TNF)-alpha, Interleukin (IL)-2 and IL-4 concentrations,
but did not affect the IL-10 values. These changes appeared to be concomitant
with changes in the concentrations of the stress markers, alpha-amylase and
cortisol. The mechanisms by which psychosocial stress can induce cytokine changes
and modify the activity of salivary alpha-amylase are not entirely understood,
and further research is thus warranted.
PMID- 27486622
TI - Patient and nurse perceptions of stressors in the intensive care unit.
AB - The objective of the study was to determine the perceptions of a group of
patients on intensive care units' (ICUs) stressors and the perceptions of nurses
on ICU patients' stressors in Turkey, and compare the differences in patients'
and nurses' perception of the stressors in ICUs. In this descriptive study, 155
patients who were admitted to medical or surgical ICUs and 152 nurses who are
employed in the same units of two training and research hospitals in Turkey were
enrolled in this study. The ICU Environmental Stressor Scale (ICUESS) was used to
determine intensive care stressors. According to total ICUESS mean scores,
patients (91.41 +/- 34.91) perceived significantly less stress than the ICU
nurses (133.23 +/- 32.20) perceived them to have. Both patients and nurses ranked
'fear of death' as the greatest stressor. Physiological stressors were identified
as the most important stressors by both patients and nurses. Patients and nurses
in medical ICUs were more affected by stressors than their counterparts in
surgical ICUs. Patients with unplanned or emergency admissions perceived higher
stress than that of patients with planned admissions. Several factors could help
reduce these stressors, such as having familiar arrangements, humane ICU
environment, individual patient assessments and appropriate nursing
interventions.
PMID- 27486623
TI - Age differences in strain and emotional reactivity to stressors in professional
careers.
AB - While age differences of workers gain increasing importance because of
demographic changes in most industrialized countries, age differences in stress
experience and resistance have been rarely addressed. In this initial empirical
study, we explore the general relationship of age and strain as a function of
three processes: (1) older workers might experience less strain because of better
coping strategies; (2) older workers might experience more strain because of
higher vulnerability; or (3) age and strain might be curvilinearly related with
highest strain reported by middle-age workers. Using both general and experience
based measures, strain and emotional reactivity to stressful job events were
reported by 274 workers aged between 18 and 65 years. Results showed an inverted
U-shaped relationship between age and strain experience.
PMID- 27486624
TI - Adolescent girls' experiences of underlying social processes triggering stress in
their everyday life: a grounded theory study.
AB - The aim of this study was to generate a theoretical model of underlying social
processes that trigger stress in adolescent girls' everyday life. In-depth
interviews regarding the experiences of stress at home, school and during leisure
time were conducted with 14 17-year-old schoolgirls. Data were analysed by means
of the grounded theory method. Stress was triggered in the interaction between
responsibility and the way in which the girls were encountered. Triggered
emotional reactions took the form of four dimensions of stress included
ambivalence, frustration, despair and downheartedness. These reactions were
dependent on whether the girls voluntary assumed responsibility for various
situations or whether they were forced, or felt they were being forced, to assume
responsibility in interaction with an encounter characterized by closeness or
distance. These forms of stress reactions could appear in one dimension and
subsequently shift to another. From the public health perspective, the generated
stress model can be used in the planning and implementation of future actions to
prevent stress and promote well-being related to stress in adolescent girls.
PMID- 27486625
TI - Work stressors and impaired sleep: rumination as a mediator.
AB - An association between stress at work and impaired sleep is theoretically
plausible and supported by empirical evidence. The current study's main aim was
to investigate how the influence of stressors is carried over into the evening
and the night. We assume that this relationship is mediated by perseverative
cognitions. We tested this assumption in two cross-sectional samples with
structural equation modeling, using bootstrapped standard errors to test for
significance. Effort-reward imbalance and time pressure were used as stressors,
and rumination as a measure for perseverative cognitions. Results show that the
stressors are related to perseverative cognitions, and these are related to
impaired sleep in both samples. Indirect effects are significant in both samples.
With rumination controlled, direct effects of stressors on sleep are only
significant in one out of four cases. Thus, there is full mediation in three out
of four cases, and partial mediation in the fourth one. Our results underscore
the notion that perseverative cognitions are crucial for transferring negative
effects of work stressors into private life, including sleep, thus hindering
individuals to successfully recover.
PMID- 27486626
TI - General job performance of first-line supervisors: the role of conscientiousness
in determining its effects on subordinate exhaustion.
AB - In an integrated test of the job demands-resources model and trait activation
theory, we predicted that the general job performance of employees who also hold
supervisory roles may act as a demand to subordinates, depending on levels of
subordinate conscientiousness. In a sample of 313 customer service call centre
employees, we found that high-conscientiousness individuals were more likely to
experience emotional exhaustion, and low-conscientiousness individuals were less
likely as the general job performance of their supervisor improved. The results
were curvilinear, such that high-conscientiousness individuals' exhaustion
levelled off with very high supervisor performance (two standard deviations above
the mean), and low-conscientiousness individuals' exhaustion levelled off as
supervisor performance improved from moderate to high. These findings suggest
high-conscientiousness employees may efficiently handle demands presented by a
low-performing coworker who is their boss, but when performance expectations are
high (i.e. high-performing boss), these achievement-oriented employees may direct
their resources (i.e. energy and time) towards performance-related efforts at the
expense of their well-being. Conversely, low-conscientiousness employees suffer
when paired with a low-performing boss, but benefit from a supervisor who
demonstrates at least moderate job performance.
PMID- 27486627
TI - Mediating effects of emotional exhaustion on the relationship between job demand
control model and mental health.
AB - This study attempted to investigate the role of emotional exhaustion as a
mediator on the relationship between job demands-control (JDC) model and mental
health. Three-wave data from 297 employees were collected. The results showed
that job demands were positively related to emotional exhaustion, and increasing
job demands will increase the level of emotional exhaustion. Job control was
negatively associated with emotional exhaustion; therefore, increasing job
control will decrease the level of emotional exhaustion. Emotional exhaustion was
negatively related to mental health. Emotional exhaustion fully mediated the
relationship between job demands and mental health, and partially mediated the
positive relationship between job control and mental health. In addition, job
control was positively associated with mental health directly. The remarkable
finding of the present study was that emotional exhaustion served as the key
mediator between the JDC model and mental health. Theoretical and managerial
implications and limitations were discussed.
PMID- 27486628
TI - Gastrointestinal Tumors.
PMID- 27486630
TI - WHO publishes an implementation framework on active tuberculosis drug-safety
monitoring and management (ADSM).
PMID- 27486629
TI - Integration of Trastuzumab, with or without Pertuzumab, into Perioperative
Chemotherapy of HER2- Positive Stomach Cancer: The INNOVATION Trial (EORTC-1203
GITCG).
PMID- 27486631
TI - Obituary: Professor Armando Sabbadin.
PMID- 27486633
TI - Overview and Summary: Societal Violence: What is Our Response?
PMID- 27486634
TI - Most important best practice? Readers say partnerships targeting readmissions.
PMID- 27486632
TI - Nucleus and gene regulation.
PMID- 27486635
TI - Largest business graduate schools for physician-executives. Ranked by number of
full-time students; data collected January-April 2016 for the 2015-16 school
year.
PMID- 27486636
TI - Top Medicare supplier organizations. Ranked by 2014 Medicare payments through
Part B.
PMID- 27486637
TI - 2016 Dentist of the Year Dr. Andy Brown.
PMID- 27486638
TI - Health Care Cyberliabilty Threats: What Email Scams Look Like and How to Avoid
Them.
PMID- 27486639
TI - The drug pricing racket.
PMID- 27486640
TI - Empagliflozin (Jardiance). Type 2 diabetes: no rush to use this drug.
AB - * In early 2016, metformin monotherapy remains the treatment of choice for most
patients with type 2 diabetes. There are several alternatives for patients in
whom metformin is poorly tolerated or ineffective. However, dapagliflozin and
canagiflozin have an unfavourable harm-benefit balance and should not be used to
enhance the action of metformin. Empagliflozin is the third glifozin to be
authorised in the European Union for the treatment of type 2 diabetes. A
randomised, double-blind, placebo-controlled trial of empaglifloznin, in
combination with other glucose-lowering drugs, involved 7020 patients with type 2
diabetes, an average glycated haemoglobin (HbA1c) concentration of about 8%, and
a history of at least one cardiovascular event. After about 3 years of follow-up,
overall mortality was lower with empagliflozin (5.7% versus 8.3%, p < 0.001),
mainly due to a reduction in cardiovascular mortality, particularly due to heart
failure. This benefit does not seem due to efficacy in preventing the
cardiovascular complications of diabetes, as there was no difference between the
groups in terms of myocardial infarction or stroke. The most likely explanation
is an effect in preventing other cardiovascular disorders, such as heart failure,
in patients with a history of cardiovascular disorders. This is consistent with
the diuretic effect of empagliflozin and its rapid impact on mortality (within a
matter of months in the trial), as well as with lower exposure to cardiovascular
drugs and reduction in the risk of hospital admission for heart failure. In seven
comparative trials, empagliflozin had only a moderate glucose-lowering action:
among patients with an average baseline HbA1c of about 8%, the HbA1c fell by
about 0.5% more with empagliflozin than with placebo. An even smaller effect was
reported in patients with renal impairment. Empagliflozin shares the adverse
effects of other gliflozins, including genital infections, kidney failure, and
diabetic ketoacidosis. Empagliflozin may also be hepatotoxic. A risk of cancer
(especially bladder cancer) cannot be ruled out. Empagliflozin interacts with
nephrotoxic drugs, which aggravate its adverse effects and decrease its
hypoglycaemic potency. The diuretic action of empagliflozin can lead to volume
depletion and a fail in blood pressure, especially during co-administration with
other diuretics or antihypertensive drugs. In practice, empagliflozin was found
to reduce mortality in a clinical trial involving patients with type 2 diabetes
and significant cardiovascular risk factors. This benefit does not seem to be
related to the hypoglycaemic effect of empagliflozin or to prevention of the
cardiovascular complications of diabetes, but rather to prevention of heart
failure in patients with history of cardiovascular disease. In early 2016, it is
unclear which patients are most likely to derive a concrete benefit from
empagliflozin therapy. Comparative evaluation must continue, especially in
patients with heart failure.
PMID- 27486641
TI - Apremilast (Otezla). No progress in plaque psoriasis or psoriatic arthritis.
AB - When PUVA therapy and immunosuppressants such as methotrexate are ineffective,
TNF alpha antagonists are an option for patients with severe plaque psoriasis, in
the absence of a better alternative. This is also the case for patients with
psoriatic arthritis after failure of a "disease-modifying" antirheumatic drug.
Apremilast, an oral immunosuppressant that inhibits phosphodiesterase type 4, has
been authorised in the European Union for use in these settings. In patients with
plaque psoriasis, oral apremilast was compared with subcutaneous etanercept, aTNF
alpha antagonist, in a randomised, doubleblind, placebo-controlled trial lasting
16 weeks and involving 250 patients in whom other treatments had failed or were
inappropriate. This trial failed to show that apremilast was more effective than
etanercept. And about one-quarter more patients experienced symptom relief
compared with placebo. In patients with psoriatic arthritis, there are no
clinical trials comparing apremilast with TNF alpha antagonists, and no
interpretable trials of apremilast after failure of a TNF alpha antagonist. In
three randomised, double-blind trials including a total of 1493 patients treated
for 16 weeks, at least a modest improvement in joint status was reported in about
35% of patients treated with apremilast versus 19% with placebo. This would
suggest that apremilast is less effective than a TNF alpha antagonist. In the
trial versus etanercept, serious adverse events occurred in 3.6% of patients
treated with apremilast versus 1.2% of those treated with the TNF alpha
antagonist. The main adverse effects of apremilast are diarrhoea, nausea and
vomiting, headache, sometimes marked weight loss, and infections. A risk of
depression and cardiac arrhythmia must also be taken into account. A risk of
cancer in the long-term is likely, given the immunosuppressive action of
apremilast. Apremilast is a substrate of cytochrome P450 isoenzyme 3A4 and
accumulates in patients with renal failure. This creates a risk of multiple
pharmacokinetic interactions.
PMID- 27486643
TI - COMMON STEM. -astine.
PMID- 27486642
TI - Efavirenz in children. Minimal evaluation.
PMID- 27486645
TI - Azithromycin: pyloric stenosis in neonates.
PMID- 27486644
TI - Sympathomimetic decongestants during pregnancy: risks for the unborn child.
AB - In addition to the risk of cardiovascular events and neurological disorders,
sympathomimetic decongestants have teratogenic potential, albeit weak, when taken
during the first trimester of pregnancy, probably through disruption of the
vascular system of the embryo and the pregnant woman. In the second and third
trimesters of pregnancy, the fetus is exposed to the same adverse effects as the
mother.
PMID- 27486646
TI - Sofosbuvir: bradycardia.
PMID- 27486647
TI - Bisphosphonates: osteonecrosis of the external auditory canal.
PMID- 27486648
TI - Oral mucositis associated with cancer therapy. Guide to first-choice treatments.
PMID- 27486650
TI - Pulmonary embolism and thrombolysis.
AB - A meta-analysis of studies including about 2000 patients with pulmonary embolism
suggests that thrombolysis slightly reduces overall mortality at one month in
patients under 65 but increases the number of major bleeding events, including
intracranial haemorrhage.
PMID- 27486649
TI - Pneumococcal conjugate vaccine: do not routinely vaccinate adults aged 65 years
and older.
AB - A randomised placebo-controlled trial of 13-valent pneumococcal conjugate vaccine
was conducted in about 84 500 adults aged 65 years and older, with no particular
risk factors. Four years on average after vaccination, there was no reduction in
either mortality or the overall incidence of community-acquired pneumonia. It was
necessary to vaccinate about 1000 individuals in order to prevent one case of
vaccine-type pneumococcal pneumonia during the 4-year follow-up period.
PMID- 27486651
TI - Drug packaging in 2015: risky industry choices and lax regulation.
AB - Prescrire examined the packaging quality of 240 drugs in 2015. No new advances
were identified, but drug packaging continues to expose patients to a variety of
dangers. Some past advances persist: for example, INNs are often more legible,
and recent patient leaflets tend to be clearer and more informative. But these
measures are not applied to all drugs, and are rarely applied retroactively to
older drugs. The overall picture in 2015 is that many drugs are difficult to
identify, risky or downright dangerous to prepare, or supplied with patient
leaflets that fail to correctly inform patients about their medication. And
measures to prevent drug poisoning in children need to be completely rethought.
It is high time for regulators and policy makers to take the issue of drug
packaging seriously, so blatant are the signs of their failure to do so: the
increasing use of bulk bottles for new drugs; failure to implement guidelines on
safe drug packaging (unit-dose presentations, appropriate dosing devices, etc.);
and expanding umbrella brands which, given the dangers they pose to patients,
should be banned instead. All things considered, healthcare professionals and
patients must remain vigilant and report any dangers they identify. A major
European initiative on drug packaging is becoming increasingly necessary.
PMID- 27486652
TI - Patient leaflet for Harvoni (sofosbuvir + ledipasvir): almost no information on
adverse effects.
PMID- 27486653
TI - Andrew Herxheimer: medicine for the people.
PMID- 27486654
TI - The finances of Association Mieux Prescrire: 2015 Prescrire annual report.
PMID- 27486655
TI - Fetoscopic Endoluminal Tracheal Occlusion in Fetuses with Severe Diaphragmatic
Hernia: A Three-Year Single-Center Experience.
AB - OBJECTIVE: To report on our experience in the prenatal treatment of severe
congenital diaphragmatic hernia (CDH) by fetoscopic endoluminal tracheal
occlusion (FETO). METHODS: Between 2012 and 2014, FETO was performed at our
center in 21 cases of CDH considered to be severe based on sonographic
measurement of observed/expected lung-to-head ratio (O/E LHR) and side of the
defect. We reported pre- and postoperative ultrasound findings, procedure-related
complications, pregnancy outcome and survival at 1-3 years of age. RESULTS: The
median gestational age (GA) at balloon insertion was 28.1 weeks (range 26.0-31.1)
and the median GA at delivery 34.7 weeks (range 31.6-39.0); delivery before 32
and 34 weeks occurred in 2 (9.5%) and 7 (33.3%) cases, respectively. Postnatal
survival at 1-3 years of age in the 17 cases with isolated unilateral CDH was
47.1%. The percentage difference between pre-balloon removal O/E LHR and pre-FETO
O/E LHR was significantly higher in survivors compared to neonates who died (40.8
vs. 21.2%, respectively; p < 0.05). CONCLUSIONS: In this study, FETO was
associated with an infant survival of 47% in cases with isolated unilateral
severe CDH. The post-FETO increase in O/E LHR was higher in fetuses that survived
compared to those who died.
PMID- 27486656
TI - Induction of Connective Tissue Growth Factor Expression by Hypoxia in Human Lung
Fibroblasts via the MEKK1/MEK1/ERK1/GLI-1/GLI-2 and AP-1 Pathways.
AB - Several reports have indicated that hypoxia, GLI, and connective tissue growth
factor (CTGF) contribute to pulmonary fibrosis in idiopathic pulmonary fibrosis.
We investigated the participation of mitogen-activated protein kinase kinase
(MEK) kinase 1 (MEKK1)/MEK1/ERK1/GLI-1/2 and activator protein-1 (AP-1) signaling
in hypoxia-induced CTGF expression in human lung fibroblasts. Hypoxia time
dependently increased CTGF expression, which was attenuated by the small
interfering RNA (siRNA) of GLI-1 (GLI-1 siRNA) and GLI-2 (GLI-2 siRNA) in both
human lung fibroblast cell line (WI-38) and primary human lung fibroblasts
(NHLFs). Moreover, GLI-1 siRNA and GLI-2 siRNA attenuated hypoxia-induced CTGF
luciferase activity, and the treatment of cells with hypoxia induced GLI-1 and
GLI-2 translocation. Furthermore, hypoxia-induced CTGF expression was reduced by
an MEK inhibitor (PD98059), MEK1 siRNA, ERK inhibitor (U0126), ERK1 siRNA, and
MEKK1 siRNA. Both PD98059 and U0126 significantly attenuated hypoxia-induced CTGF
luciferase activity. Hypoxia time-dependently increased MEKK1, ERK, and p38 MAPK
phosphorylation. Moreover, SB203580 (a p38 MAPK inhibitor) also apparently
inhibited hypoxia-induced CTGF expression. The treatment of cells with hypoxia
induced ERK, GLI-1, or GLI-2 complex formation. Hypoxia-induced GLI-1 and GLI-2
translocation into the nucleus was significantly attenuated by U0126. In
addition, hypoxia-induced ERK Tyr204 phosphorylation was impeded by MEKK1 siRNA.
Moreover, hypoxia-induced CTGF-luciferase activity was attenuated by cells
transfected with AP-1 site mutation in a CTGF construct. Exposure to hypoxia
caused a time-dependent phosphorylation of c-Jun, but not of c-Fos. Chromatin
immunoprecipitation (ChIP) revealed that hypoxia induced the recruitment of c
Jun, GLI-1, and GLI-2 to the AP-1 promoter region of CTGF. Hypoxia-treated cells
exhibited an increase in alpha-smooth muscle actin (alpha-SMA) and collagen
production, which was blocked by GLI-1 siRNA and GLI-2 siRNA. Overall, these data
implied that the MEKK1/MEK1/ERK1/GLI-1/GLI-2, and AP-1 pathways mediated hypoxia
induced CTGF expression in human lung fibroblasts. Furthermore, GLI-1 and GLI-2
found to be involved in hypoxia-induced alpha-SMA and collagen expression.
PMID- 27486657
TI - Increased Echogenicity and Radiodense Foci on Echocardiogram and MicroCT in
Murine Myocarditis.
AB - OBJECTIVES: To address the question as to whether echocardiographic and/or
microcomputed tomography (microCT) analysis can be utilized to assess the extent
of Coxsackie B virus (CVB) induced myocarditis in the absence of left ventricular
dysfunction in the mouse. BACKGROUND: Viral myocarditis is a significant clinical
problem with associated inflammation of the myocardium and myocardial injury.
Murine models of myocarditis are commonly used to study the pathophysiology of
the disease, but methods for imaging the mouse myocardium have been limited to
echocardiographic assessment of ventricular dysfunction and, to a lesser extent,
MRI imaging. METHODS: Using a murine model of myocarditis, we used both
echocardiography and microCT to assess the extent of myocardial involvement in
murine myocarditis using both wild-type mice and CVB cleavage-resistant
dystrophin knock-in mice. RESULTS: Areas of increased echogenicity were only
observed in the myocardium of Coxsackie B virus infected mice. These
echocardiographic abnormalities correlated with the extent of von Kossa staining
(a marker of membrane permeability), inflammation, and fibrosis. Given that
calcium phosphate uptake as imaged by von Kossa staining might also be visualized
using microCT, we utilized microCT imaging which allowed for high-resolution, 3
dimensional images of radiodensities that likely represent calcium phosphate
uptake. As with echocardiography, only mice infected with Coxsackie B virus
displayed abnormal accumulation of calcium within individual myocytes indicating
increased membrane permeability only upon exposure to virus. CONCLUSIONS: These
studies demonstrate new, quantitative, and semi-quantitative imaging approaches
for the assessment of myocardial involvement in the setting of viral myocarditis
in the commonly utilized mouse model of viral myocarditis.
PMID- 27486659
TI - The Distribution of Climate Change Public Opinion in Canada.
AB - While climate scientists have developed high resolution data sets on the
distribution of climate risks, we still lack comparable data on the local
distribution of public climate change opinions. This paper provides the first
effort to estimate local climate and energy opinion variability outside the
United States. Using a multi-level regression and post-stratification (MRP)
approach, we estimate opinion in federal electoral districts and provinces. We
demonstrate that a majority of the Canadian public consistently believes that
climate change is happening. Belief in climate change's causes varies
geographically, with more people attributing it to human activity in urban as
opposed to rural areas. Most prominently, we find majority support for carbon cap
and trade policy in every province and district. By contrast, support for carbon
taxation is more heterogeneous. Compared to the distribution of US climate
opinions, Canadians believe climate change is happening at higher levels. This
new opinion data set will support climate policy analysis and climate policy
decision making at national, provincial and local levels.
PMID- 27486658
TI - Natalizumab Affects T-Cell Phenotype in Multiple Sclerosis: Implications for JCV
Reactivation.
AB - The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy
against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab
therapeutic efficacy is limited by the reactivation of the John Cunningham
polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy
(PML). To correlate natalizumab-induced phenotypic modifications of peripheral
blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV
DNA (blood and urine), CD49d expression and relative abundance of peripheral
blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated
RRMS patients. Statistical analyses were performed using GraphPad Prism and R.
Natalizumab treatment reduced CD49d expression on memory and effector subsets of
peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+
memory and effector cells was observed after 12 and 24 months of treatment. CD4+
and CD8+ T-lymphocyte immune-activation was increased after 24 months of
treatment. Higher percentages of CD8+ effectors were observed in subjects with
detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte
memory and effector subsets, limiting their migration to the central nervous
system and determining their accumulation in peripheral blood. Impairment of
central nervous system immune surveillance and reactivation of latent JCV, can
explain the increased risk of PML development in natalizumab-treated RRMS
subjects.
PMID- 27486660
TI - Effect of Novel, School-Based High-Intensity Interval Training (HIT) on
Cardiometabolic Health in Adolescents: Project FFAB (Fun Fast Activity Blasts) -
An Exploratory Controlled Before-And-After Trial.
AB - BACKGROUND: Low-volume high-intensity interval training holds promise for
cardiometabolic health promotion in adolescents, but sustainable interventions
must be practical and engaging. We examined the effect of a school-based multi
activity low-volume high-intensity interval training intervention on adolescents'
cardiometabolic health. METHODS: In an exploratory controlled before-and-after
design, 101 adolescents (mean age +/- standard deviation [SD] 14.0 +/- 0.3 years)
were recruited from four schools; two were designated as intervention sites (n =
41), and two as control (n = 60). The intervention comprised 4 to 7 repetitions
of 45 s maximal effort exercise (basketball, boxing, dance and soccer drills)
interspersed with 90-s rest, thrice weekly for 10 weeks. Outcomes were non
fasting blood lipids and glucose, waist circumference, high sensitivity C
reactive protein, resting blood pressure, physical activity, twenty-metre shuttle
run test performance and carotid artery intima-media thickness. The difference in
the change from baseline (intervention minus control) was estimated for each
outcome. Using magnitude-based inferences, we calculated the probability that the
true population effect was beneficial, trivial, and harmful against a threshold
for the minimum clinically important difference of 0.2 between-subject SDs.
RESULTS AND DISCUSSION: Mean (+/- SD) attendance for the intervention (expressed
as percentage of available intervention sessions [n = 30]) was 77 +/- 13%. Post
intervention, there were likely beneficial effects for triglycerides (-26%; 90%
confidence interval -46% to 0%), waist circumference (-3.9 cm; -6.1 cm to -1.6
cm) and moderate-to-vigorous physical activity (+16 min; -5 to 38 min), and a
possibly beneficial effect for twenty-metre shuttle-run test performance (+5
shuttles; -1 to 11 shuttles) in intervention participants (vs controls). The role
of elevated triglycerides and waist circumference in cardiovascular disease and
metabolic syndrome development underlines the importance of our findings. We also
demonstrated that school-based low-volume high-intensity interval training can be
delivered as intended, thus representing a novel and scalable means of improving
aspects of adolescents' cardiometabolic health. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02626767.
PMID- 27486661
TI - Tourniquet Test for Dengue Diagnosis: Systematic Review and Meta-analysis of
Diagnostic Test Accuracy.
AB - BACKGROUND: Dengue fever is a ubiquitous arboviral infection in tropical and sub
tropical regions, whose incidence has increased over recent decades. In the
absence of a rapid point of care test, the clinical diagnosis of dengue is
complex. The World Health Organisation has outlined diagnostic criteria for
making the diagnosis of dengue infection, which includes the use of the
tourniquet test (TT). PURPOSE: To assess the quality of the evidence supporting
the use of the TT and perform a diagnostic accuracy meta-analysis comparing the
TT to antibody response measured by ELISA. DATA SOURCES: A comprehensive
literature search was conducted in the following databases to April, 2016:
MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, BIOSIS,
Web of Science, SCOPUS. STUDY SELECTION: Studies comparing the diagnostic
accuracy of the tourniquet test with ELISA for the diagnosis of dengue were
included. DATA EXTRACTION: Two independent authors extracted data using a
standardized form. DATA SYNTHESIS: A total of 16 studies with 28,739 participants
were included in the meta-analysis. Pooled sensitivity for dengue diagnosis by TT
was 58% (95% Confidence Interval (CI), 43%-71%) and the specificity was 71% (95%
CI, 60%-80%). In the subgroup analysis sensitivity for non-severe dengue
diagnosis was 55% (95% CI, 52%-59%) and the specificity was 63% (95% CI, 60%
66%), whilst sensitivity for dengue hemorrhagic fever diagnosis was 62% (95% CI,
53%-71%) and the specificity was 60% (95% CI, 48%-70%). Receiver-operator
characteristics demonstrated a test accuracy (AUC) of 0.70 (95% CI, 0.66-0.74).
CONCLUSION: The tourniquet test is widely used in resource poor settings despite
currently available evidence demonstrating only a marginal benefit in making a
diagnosis of dengue infection alone. REGISTRATION: The protocol for this
systematic review was registered at PROSPERO: CRD42015020323.
PMID- 27486662
TI - Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive
Status Epilepticus or Prolonged Seizure Episode after Convulsive Status
Epilepticus - A MRI Study Using Susceptibility Weighted Imaging.
AB - OBJECTIVE: The aim of this study was to investigate variant patterns of cortical
venous oxygenation during status epilepticus (SE) using susceptibility-weighted
imaging (SWI). METHODS: We analyzed magnetic resonance imaging (MRI) scans of 26
patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE.
All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI
DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns
of SWI signal alterations that revealed regional or global increases of cerebral
blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related
oxygenation patterns reflect ictal or postictal patterns that resemble SE or
sequelae of seizures. RESULTS: Sixteen patients were examined during
nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten
patients suffered from witnessed and prolonged seizure episode ahead of imaging
without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized
hyperoxygenation by SWI in keeping with either global or multifocal cortical
hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related
to focal CBF increase and three patients showed a focal deoxygenation pattern
related to focal CBF decrease. CONCLUSIONS: SWI-related hyper- and deoxygenation
patterns resemble ictal and postictal CBF changes within a range from globally
increased to focally decreased perfusion. In all 26 patients the SWI patterns
were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or
postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of
this study is that cortical venous patterns in SWI can be not only focally, but
globally attenuated. SWI may thus be considered as an alternative contrast-free
MR sequence to identify perfusion changes related to ictal or postictal
conditions.
PMID- 27486663
TI - Kinetic Study of Acetone-Butanol-Ethanol Fermentation in Continuous Culture.
AB - Acetone-butanol-ethanol (ABE) fermentation by clostridia has shown promise for
industrial-scale production of biobutanol. However, the continuous ABE
fermentation suffers from low product yield, titer, and productivity. Systems
analysis of the continuous ABE fermentation will offer insights into its
metabolic pathway as well as into optimal fermentation design and operation. For
the ABE fermentation in continuous Clostridium acetobutylicum culture, this paper
presents a kinetic model that includes the effects of key metabolic intermediates
and enzymes as well as culture pH, product inhibition, and glucose inhibition.
The kinetic model is used for elucidating the behavior of the ABE fermentation
under the conditions that are most relevant to continuous cultures. To this end,
dynamic sensitivity analysis is performed to systematically investigate the
effects of culture conditions, reaction kinetics, and enzymes on the dynamics of
the ABE production pathway. The analysis provides guidance for future metabolic
engineering and fermentation optimization studies.
PMID- 27486664
TI - Detection and Characterization of Low Temperature Peat Fires during the 2015 Fire
Catastrophe in Indonesia Using a New High-Sensitivity Fire Monitoring Satellite
Sensor (FireBird).
AB - Vast and disastrous fires occurred on Borneo during the 2015 dry season, pushing
Indonesia into the top five carbon emitting countries. The region was affected by
a very strong El Nino-Southern Oscillation (ENSO) climate phenomenon, on par with
the last severe event in 1997/98. Fire dynamics in Central Kalimantan were
investigated using an innovative sensor offering higher sensitivity to a wider
range of fire intensities at a finer spatial resolution (160 m) than heretofore
available. The sensor is onboard the TET-1 satellite, part of the German
Aerospace Center (DLR) FireBird mission. TET-1 images (acquired every 2-3 days)
from the middle infrared were used to detect fires continuously burning for
almost three weeks in the protected peatlands of Sebangau National Park as well
as surrounding areas with active logging and oil palm concessions. TET-1
detection capabilities were compared with MODIS active fire detection and Landsat
burned area algorithms. Fire dynamics, including fire front propagation speed and
area burned, were investigated. We show that TET-1 has improved detection
capabilities over MODIS in monitoring low-intensity peatland fire fronts through
thick smoke and haze. Analysis of fire dynamics revealed that the largest burned
areas resulted from fire front lines started from multiple locations, and the
highest propagation speeds were in excess of 500 m/day (all over peat > 2m deep).
Fires were found to occur most often in concessions that contained drainage
infrastructure but were not cleared prior to the fire season. Benefits of
implementing this sensor system to improve current fire management techniques are
discussed. Near real-time fire detection together with enhanced fire behavior
monitoring capabilities would not only improve firefighting efforts, but also
benefit analysis of fire impact on tropical peatlands, greenhouse gas emission
estimations as well as mitigation measures to reduce severe fire events in the
future.
PMID- 27486666
TI - Nd:YAG Laser Treatment for Extranasal Telangiectasias: A Retrospective Analysis
of 38 Patients with Hereditary Hemorrhagic Telangiectasia and Review of the
Literature.
AB - BACKGROUND/AIMS: Extranasal telangiectasias are common amongst hereditary
hemorrhagic telangiectasia (HHT) patients. Telangiectasias can be found at sites
like the external nose, lips, oral cavity and fingers. Although not life
threatening, they can be annoying for patients and lead to bleeding in some
cases, necessitating treatment. METHODS: The data of 38 HHT patients treated for
extranasal telangiectasias during a period of 10 years by means of Nd:YAG laser
were retrospectively analyzed. RESULTS: The telangiectasias treated affected
predominantly the tongue, facial skin and lips. During a minimum follow-up of 3
years, only 7 patients required a revision of surgery. CONCLUSION: This study
shows that Nd:YAG laser constitutes a fast, safe and efficient therapeutic
modality for the treatment of extranasal telangiectasias.
PMID- 27486667
TI - Significant Association between Toll-Like Receptor Gene Polymorphisms and
Posttransplantation Diabetes Mellitus.
AB - BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is an important
metabolic complication after renal transplantation. Activation of the innate
immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of
insulin resistance and deficiency. Although links between diabetes, dysregulated
innate immune responses, and the TLR signaling pathway have been reported, no
study so far has investigated their associations with PTDM. In this study, we
ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated
with PTDM in the Korea population. METHODS: A total of 305 patients who received
renal transplants without previously diagnosed diabetes were included. We
analyzed the association between PTDM development and 6 SNPs within 2 genes of
TLR2, 1 gene of TLR4, and 3 genes of TRL6. RESULTS: Of 305 patients, PTDM
developed in 51 patients (16.6%). Patients in the PTDM group were older than
those in the non-PTDM group (45.56 +/- 1.28 vs. 38.28 +/- 0.71 years). Patients
with PTDM had significantly higher allele frequency compared to those without
PTDM for the TLR4 rs1927914*T, TLR6 rs3775073*A, TLR6 rs3821985*C, and TLR6
rs1039559*C alleles. Of the 6 SNPs, rs1927914 in the TLR4 gene and rs1039559 in
the TLR6 gene were significantly associated with the development of PTDM after
adjustment for age, gender, and tacrolimus usage. CONCLUSIONS: Our study
demonstrates a significant association between SNPs rs1927914 in TLR4 and
rs1039559 in TLR6 and PTDM in the renal transplantation recipient group. These
data suggest that the activation of the innate immune system and inflammation via
TLR activation might have an essential role in the pathogenesis of PTDM in renal
transplantation.
PMID- 27486665
TI - Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection.
AB - The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor
underlying progressive HIV infection, but whether HIV-specific CD8+ T cells
initially possess cytolytic effector capacity, and when and why this may be lost
during infection, is unclear. Here, we assessed CD8+ T cell functional evolution
from primary to chronic HIV infection. We observed a profound expansion of
perforin+ CD8+ T cells immediately following HIV infection that quickly waned
after acute viremia resolution. Selective expression of the effector-associated
transcription factors T-bet and eomesodermin in cytokine-producing HIV-specific
CD8+ T cells differentiated HIV-specific from bulk memory CD8+ T cell effector
expansion. As infection progressed expression of perforin was maintained in HIV
specific CD8+ T cells with high levels of T-bet, but not necessarily in the
population of T-betLo HIV-specific CD8+ T cells that expand as infection
progresses. Together, these data demonstrate that while HIV-specific CD8+ T cells
in acute HIV infection initially possess cytolytic potential, progressive
transcriptional dysregulation leads to the reduced CD8+ T cell perforin
expression characteristic of chronic HIV infection.
PMID- 27486668
TI - Is It Desirable that I Must Disclose My Genetic Data to Swiss Private Medical
Insurances?
AB - Genetic testing has far-reaching consequences, not only in terms of immediate
patient management and the wider implications for the patient and their families,
but also with respect to disclosure to insurance companies. The focus of this
review is the controversial but important topic of the use of genetic data in
private medical insurance. We discuss the current legal regulation of genetic
data in the context of Swiss insurance, what type(s) of information is relevant
to insurance companies, and why 'genetic exceptionalism' (the notion that genetic
data has special status) persists. Furthermore, we discuss the sensitive area of
handling genetic data from children. The consequences of legal regulation of
disclosure of genetic information are considered, particularly from the economic
perspective. Finally, we examine how legal conditions correspond to current
insurance practice and contrast the Swiss system with the handling of genetic
data in other countries in the context of private insurance. Switzerland has
adopted fairly 'laissez-faire' regulations compared to other countries, and the
public need education on the potential effects of genetic testing on their
insurance, especially with respect to direct-to-consumer genetic testing, where
there is no consultation from a qualified doctor, or when minors are involved.
PMID- 27486670
TI - Deep-Red and Near-Infrared Xanthene Dyes for Rapid Live Cell Imaging.
AB - In this work, two xanthene dyes (H-hNR and TF-hNR) have been synthesized by a
convenient and efficient method. These two dyes exhibited deep-red and near
infrared emissions, high fluorescence quantum yields, and good photostability.
Their structure-optical properties were investigated by X-ray crystal structure
analysis and density functional theory calculations. Live cell imaging data
revealed that H-hNR and TF-hNR could rapidly stain both A549 and HeLa cells with
low concentrations. The excellent photophysical and imaging properties render
them as promising candidates for use in live cell imaging.
PMID- 27486671
TI - Relationship between mechanical properties and crystal structure in cocrystals
and salt of paracetamol.
AB - Objectives were to study mechanical properties of various solid forms of
paracetamol and relate to their crystal structures. Paracetamol form I (PRA), its
cocrystals with oxalic acid (PRA-OXA) and 4,4-bipyridine (PRA-BPY) and
hydrochloride salt (PRA-HCL) were selected. Cocrystals and salt were scaled-up
using rational crystallization methods. The resulting materials were subjected to
different solid-state characterizations. The powders were sieved and 90-360 um
sieve fraction was considered. These powders were examined by scanning electron
microscopy (SEM) and densities were determined. Tablets were made at applied
pressures of 35-180 MPa under controlled conditions and the tablet height,
diameter and hardness were measured. Tensile strength and porosity of the tablets
were estimated using well known models. Crystal structures of these systems were
visualized and slip planes were identified. Cocrystal and salt of PRA were
physically pure. Sieved powders had comparable morphologies and particle size.
The apparent and theoretical densities of powders were similar, but no clear
trends were observed. The tensile strengths of these compacts were increased with
increasing pressure whereas tabletability decreased in the order oxalic acid >
PRA-HCL ~ PRA-OXA > BPY > PRA-BPY. Tablet tensile strength decreases
exponentially with increasing porosity with the exception of PRY-BPY and BPY.
Slip plane prediction based on attachment energies may not be independently
considered. However, it was possible to explain the improved mechanical
properties of powders based on the crystal structure. Cocrystallization and salt
formation have introduced structural features that are responsible for improved
tableting properties of PRA.
PMID- 27486669
TI - Risk of Invasive Meningococcal Disease in Men Who Have Sex with Men: Lessons
Learned from an Outbreak in Germany, 2012-2013.
AB - BACKGROUND: We undertook investigations in response to an invasive meningococcal
disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012-2013 to
better understand meningococcal transmission and IMD risk in MSM. METHODS: We
retrospectively searched for further IMD cases in MSM in Germany through local
health departments and undertook exploratory interviews. We performed antigen
sequence typing, characterized fHbp and aniA genes of strains with the outbreak
finetype and reviewed epidemiologically or spatiotemporally linked cases from
2002-2014. RESULTS: Among the 148 IMD-cases notified from 01.01.2012-30.09.2013
in 18-59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C
(MenC, all finetype C:P1.5-1,10-8:F3-6), 2 MenB. Interviews with 7 MSM revealed
frequent meeting of multiple partners online or via mobile apps and illicit drug
use as potential risk factors. MenC incidence was 13-fold higher in MSM than non
MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5-1,10
8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p =
0.04). Although definitive evidence for transmission among MSM in epidemiological
or spatiotemporal clusters in 2002-2014 was lacking, clusters were more frequent
in men aged 20-49 years. Molecular analysis of C:P1.5-1,10-8:F3-6 strains
revealed cases with intact aniA since 2007, mainly associated with fHbp361,
fHbp766 and fHbp813, all involving one or more MSM. CONCLUSIONS: MenC incidence
was elevated in MSM during the study period. Multiple casual sexual contacts and
illicit drug use were common in affected MSM. In all strains from MSM we detected
an intact aniA gene coding for a nitrite reductase, which permits survival in
microanaerobic environments and could play a role in meningococcal transmission
in MSM through urogenital colonization. Furthermore, meningococcal transmission
among MSM may be sustained over large areas and thus require modified
spatiotemporal scanning algorithms for timely detection and control.
PMID- 27486672
TI - Active Somatic and Psychic Ear Acupuncture Points in Newborn Infants with
Neonatal Abstinence Syndrome.
AB - BACKGROUND: Neonatal abstinence syndrome (NAS) occurs within the first days after
birth in newborns of mothers with a history of drug abuse. It may also occur in
newborns whose mothers are undergoing substitution therapy. OBJECTIVE: To
determine the presence of active ear acupuncture points in newborn infants with
NAS. METHODS: Among newborn infants with NAS admitted to the Division of
Neonatology at the University Hospital Graz between March 2009 and November 2014,
an acupuncture-point detector (PS3 Silberbauer, Vienna, Austria) was used to
identify active ear acupuncture points. An integrated optical and acoustical
signal detects the ear points, which were then assigned to the ear map. A total
of 31 newborn infants were assessed; 1 infant was excluded, however, because the
mother had already weaned herself off opiates before admission. RESULTS: The
excluded infant did not develop signs of NAS, had a low Finnegan score (3
points), and did not present any detectable active psychic ear acupuncture
points. In all included newborn infants with NAS, active ear acupuncture points
were identified: The psychovegetative rim was the most common active somatic area
in each infant, followed by a few somatic and psychic ear acupuncture points. In
all infants with symptoms of NAS, active psychic ear points were identified, of
which the most frequently found points were the Frustration point and the R
point. CONCLUSION: The activity of psychic ear acupuncture points may be specific
for neonates with NAS.
PMID- 27486673
TI - Pyclen Tri-n-butylphosphonate Ester as Potential Chelator for Targeted
Radiotherapy: From Yttrium(III) Complexation to (90)Y Radiolabeling.
AB - The Y(3+) complex of PCTMB, the tri-n-butyl phosphonate ester of pyclen (3,6,9,15
tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene), was synthesized as well as
its Ho(3+) and Lu(3+) analogues. X-ray diffraction analyses revealed isomorphous
dimeric M2(PCTMB)2.9H2O (M = Y, Ho, Lu) structures that crystallize in the
centrosymmetric P1 triclinic space group. (1)H NMR and UV studies in aqueous
solutions indicated that Y(3+) complexation is fast, being quantitative in 167
min at pH 3.8 and in 13 min at pH 5.5 (25 degrees C, acetate buffer, I = 0.150
M, [Y(3+)] = [PCTMB] = 0.2 mM). (1)H NMR DOSY and photon correlation spectroscopy
experiments evidenced the formation of aggregates in chloroform with a bimodal
distribution that changes slightly with concentration (11-24 and 240-258 nm). The
behavior of the acid-assisted dissociation of the complex of Y(3+) with PCTMB was
studied under pseudo-first-order conditions, and the half-life of the [Y(PCTMB)]
complex in 0.5 M HCl at 25 degrees C was found to be 37 min, a value that
decreases to 2.6 min in 5 M HCl. The Y(3+) complex of PCTMB is thermodynamically
very stable, with a stability constant of log KY-PCTMB = 19.49 and pY = 16.7
measured by potentiometry. (90)Y complexation studies revealed fast radiolabeling
kinetics; optimal radiolabeling conditions were obtained for (90)Y in acetate
medium, PCTMB at 10(-4) to 10(-2) M in acetate buffer pH = 4.75, 15 min at 45-60
degrees C. In vitro stability studies in human serum showed that [(90)Y(PCTMB)]
is quite stable, with about 90% of the activity still in the form of the
radiotracer at 24 h and 80% from 48 h to 72 h. A comparison with other ligands
such as PCTA, DOTA, and DTPA already used for in vivo application shows that
[(90)Y(PCTMB)] is an interesting lipophilic and neutral analogue of these
reference chelates for therapeutic applications in aqueous and nonaqueous media.
PMID- 27486674
TI - Total Synthesis of Leupyrrin B1: A Potent Inhibitor of Human Leukocyte Elastase.
AB - The total synthesis of leupyrrin B1 was accomplished by an expedient strategy
that involves an optimized HATU-mediated amide coupling protocol of elaborate
substrates. The generally useful procedure was also successfully applied in an
improved total synthesis of leupyrrin A1. Finally, leupyrrins A1 and B1 were
evaluated toward a panel of proteases, and human leukocyte elastase was
discovered as a molecular target of the leupyrrins.
PMID- 27486675
TI - Influence of Water on the Interfacial Nanostructure and Wetting of [Rmim][NTf2]
Ionic Liquids at Mica Surfaces.
AB - The effect of water concentration on the interfacial nanostructure and wetting
behavior of a family of ionic liquids (ILs), 1-alkyl-3-methylimidazolium
bis(trifluoromethanesulfonyl)imide, [Rmim][NTf2], at the surface of mica was
investigated by contact angle measurement and atomic force microscopy (AFM). AFM
reveals that interfacial layers of ILs observed at the surface of mica for "dry"
ILs are not present for water-saturated ILs. The interaction of the IL ions of
[Rmim][NTf2] with water molecules through hydrogen bonding is suspected to
disrupt IL ion layering and precursor film growth on mica. Without the IL
precursor film, contact angle relaxation of "wet" ILs on mica is less significant
and ambient vapor adsorption becomes more important in determining the
macroscopic wetting behavior.
PMID- 27486676
TI - Neuroprotection by intravenous transplantation of bone marrow mononuclear cells
from 5-fluorouracil pre-treated rats in a model of ischemic stroke.
AB - Our previous studies showed that bone marrow mononuclear cells (BMMNCs) from 5
fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic
efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats.
This study was undertaken to further explore the potential mechanisms underlying
the neuroprotective effects of BMRMNCs in the same model. Rats were intravenously
pre-treated with 5-FU, and BMRMNCs were collected 7 days later and subjected to
flow cytometry for detection of CD34, CD45 and CD90. Middle cerebral artery
occlusion (MCAO) was induced in rats, and BMMNCs and BMRMNCs were independently
transplanted via the tail vein at 24 h after MCAO. NISSL staining was performed
14 days after cell transplantation and the viable cells in the hippocampus were
counted. Stromal cell-derived factor 1 (SDF-1) mRNA expression was detected in
the penumbra at 7 and 14 days after treatment. The contents of pro-inflammatory
cytokines and growth factors as well as microvessel density (MVD) were determined
at 14 days. Results showed more BMRMNCs were positive for CD34, CD45 and CD90.
After transplantation, more viable cells were observed in the hippocampus of
BMRMNCs treated rats. In addition, BMRMNCs transplantation significantly
increased MVD, reduced pro-inflammatory cytokines and raised growth factors in
the penumbra. However, the SDF-1 mRNA expression was comparable between BMRMNCs
group and BMMNCs group. Our results indicate that BMRMNCs are likely to more
effectively improve the local microenvironment to increase viable cells and
elevate angiogenesis, exerting neuroprotective effects on cerebral ischemia in
rats.
PMID- 27486677
TI - An evaluation of the effectiveness of self-management interventions for people
with type 2 diabetes after an acute coronary syndrome: a systematic review.
AB - BACKGROUND: Type 2 diabetes is highly prevalent in patients with acute coronary
syndrome and impacts negatively on health outcomes and self-management. Both
conditions share similar risk factors. However, there is insufficient evidence on
the effectiveness of combined interventions to promote self-management behaviour
for people with diabetes and cardiac problems. Identifying critical features of
successful interventions will inform future integrated self-management programmes
for patients with both conditions. OBJECTIVES: To assess the evidence on the
effectiveness of existing interventions to promote self-management behaviour for
patients presenting with acute coronary syndrome and type 2 diabetes in secondary
care settings and postdischarge. DESIGN: We searched MEDLINE, PubMed, CINAHL
Plus, PsycInfo, Cochrane Library and AMED for randomised controlled trials
published between January 2005-December 2014. The search was performed using the
following search terms of 'acute coronary syndrome', 'type 2 diabetes' and 'self
management intervention' and their substitutes combined. RESULTS: Of 4275
articles that were retrieved, only four trials met all the inclusion criteria
(population, intervention, comparison and outcome) and were analysed. Overall,
the results show that providing combined interventions for patients with both
conditions including educational sessions supported by multimedia or
telecommunication technologies was partially successful in promoting self
management behaviours. Implementation of these combined interventions during
patient's hospitalisation and postdischarge was feasible. Intervention group
subjects reported a significant improvement in self-efficacy, level of knowledge,
glycated haemoglobin, blood pressure and fasting glucose test. However, there are
many threats have been noticed around internal validity of included studies that
could compromise the conclusions drawn. CONCLUSION: With limited research in this
area, there was no final evidence to support effectiveness of combined
interventions to promote self-management behaviour for patients with type 2
diabetes and acute coronary syndrome. Sufficiently powered, good quality, well
conducted and reported randomised controlled trials are required.
PMID- 27486679
TI - Writing Out Loud: To Computers, Patients, and Burnout, 2016.
PMID- 27486680
TI - Cutting the cost of carbon capture: a case for carbon capture and utilization.
AB - A significant part of the cost for carbon capture and storage (CCS) is related to
the compression of captured CO2 to its supercritical state, at 150 bar and
typically 99% purity. These stringent conditions may however not always be
necessary for specific cases of carbon capture and utilization (CCU). In this
manuscript, we investigate how much the parasitic energy of an adsorbent-based
carbon capture process may be lowered by utilizing CO2 at 1 bar and adapting the
final purity requirement for CO2 from 99% to 70% or 50%. We compare different CO2
sources: the flue gases of coal-fired or natural gas-fired power plants and
ambient air. We evaluate the carbon capture performance of over 60 nanoporous
materials and determine the influence of the initial and final CO2 purity on the
parasitic energy of the carbon capture process. Moreover, we demonstrate the
underlying principles of the parasitic energy minimization in more detail using
the commercially available NaX zeolite. Finally, the calculated utilization cost
of CO2 is compared with the reported prices for CO2 and published costs for CCS.
PMID- 27486678
TI - Gender and Alcohol Use Disorders Diagnostic Criteria in Emergency Department
Patients of Argentina.
AB - BACKGROUND: Alcohol consumption and its related consequences are not equal for
women and men, although related studies do not frequently include gender
analysis. OBJECTIVE: Our aim was to characterize differences in endorsement of
ICD-10 and DSM 5 alcohol use disorder (AUD) criteria by gender in an Argentinean
emergency department population. METHODS: A probability sample of patients (N =
923) from the largest emergency department in the city of Mar del Plata,
Argentina (44% were females, aged 16 to 86, M (SD) = 37.31(15.20) was collected.
Using a structured questionnaire, diagnostic criteria for alcohol use disorders,
alcohol consumption, and socio-demographic variables were obtained. Bivariate and
multivariate analyses were used to assess differences in the endorsement of each
diagnostic criterion by gender. RESULTS: Women were less likely to endorse each
of the criteria for each of the diagnostic schemes. Even after controlling
alcohol consumption, socio-demographic variables, severity of alcohol use
disorders and adjusting for multiple comparisons females had a lower probability
than males of endorsing withdrawal and impaired control. CONCLUSIONS: gender
differences in the endorsement of diagnostic criteria for both the DSM 5 and ICD
10 were found. Some differences in endorsement but not all, might be partially
explained by alcohol consumption patterns and socio-demographic factors, and same
remained after controlling severity of the AUD. Results also suggest a
differential functioning of DSM 5 and ICD-10 AUD criteria for women and men.
PMID- 27486681
TI - Exercise therapy in patients with hip osteoarthritis: Effect on hip muscle
strength and safety aspects of exercise-results of a randomized controlled trial.
AB - PURPOSE: To evaluate the effect of an exercise therapy concept (the Tubingen
exercise therapy approach THuKo) for increasing hip muscle strength (HMS) in
patients with hip osteoarthritis (OA), and to investigate whether patients do
adhere to the intervention and if there are any adverse events related to the
intervention. METHODS: A total of 210 hip OA patients (89 females, 121 males)
were randomized into a 12-week exercise intervention (THuKo) including group
sessions (1/week) and home exercising (2/week), a placebo ultrasound group
(1/week) or a control group (no treatment). HMS was measured as isometric peak
torque of hip abduction, adduction, flexion, and extension. Adherence to exercise
and safety aspects were monitored as additional outcomes. RESULTS: Baseline
adjusted post intervention HMS of the THuKo group were higher compared to the
control group (differences of 0.11-0.27 Nm/kg, p < 0.01) and to the placebo
ultrasound group (differences of 0.09-0.19 Nm/kg, p < 0.01). Adherence to
exercise was high (about 90%). No subject had to refuse from training because of
an exercise related adverse event and exercise related pain was only of
intermittent nature without sustainable adverse effects. CONCLUSIONS: The
Tubingen exercise therapy approach has shown to have a significant positive
effect on HMS. Its implementation has shown to be feasible and safe according to
the percentage of exercise participation and the absence of sustainable adverse
events.
PMID- 27486682
TI - Hematopoiesis in Bivalvia larvae: Cellular origin, differentiation of hemocytes,
and neoplasia.
AB - Hemocytes play vital roles in the immune response. Despite progress in the
characterization of molluscan hemocytes and immune cells, including their
cellular receptors and signal transduction pathways, the processes that lead to
their differentiation in bivalve larvae remain unknown. Furthermore, the
molecular mechanisms of that decide hemocyte stem cell fate and self-renewal
during development remain poorly characterized. Similar to adult mollusks, the
larvae are filter feeders and are highly susceptible to pathogens and biotoxins;
therefore, it is important to understand the development and function of their
immune system. This review summarizes the current data on the appearance of
elements of the immune system in bivalve larvae. I have discussed why the immune
cells emerge before the circular blood vessel system, which differentiates at the
late stages of development. I also discuss how molluscan hemocytes are involved
in the development of disseminated neoplasia.
PMID- 27486683
TI - Leukocyte susceptibility and immune response against Vibrio parahaemolyticus in
Totoaba macdonaldi.
AB - Vibrio parahaemolyticus is a serious pathogen that affects aquaculture.
Nonetheless, to the best of our knowledge, no studies have focused on its
immunological implications in Totoaba macdonaldi. Thus, the early immune response
to V. parahaemolyticus in juveniles of totoaba was studied at 24 h post-infection
with an in vivo study. In addition, changes in cellular innate immune parameters
phagocytosis, respiratory burst activity and viability (annexin V/propidium
iodide) - were evaluated in vitro in head-kidney, spleen and thymus leukocytes at
6 and 24 h after bacterial stimulation by flow cytometry. Simultaneously, the
expression levels of two immune-relevant genes (IL-1beta and IL-8) were measured
by using real time PCR. During in vivo study, mRNA transcripts of IL-1beta were
highly expressed in spleen, thymus and intestine and down-regulated in liver
after 24 h post-infection. IL-8 gene expression was upregulated in spleen,
intestine and liver compared to that of non-infected fish and down-regulated in
thymus after 24 h post-infection. Generally, the results showed a significant
decrease in cellular immune responses during the infection, principally in
phagocytic ability and respiratory burst. The survival or viability of stimulated
leukocytes was significantly reduced causing necrosis and apoptosis, indicating a
robust killing response by V. parahaemolyticus. Finally the in vitro analysis
showed that transcript levels of IL-1beta and IL-8 were up-regulated during
stimulation with V. parahaemolyticus in head-kidney, spleen and intestine and
down-regulated in thymus at any time of the experiment. Although V.
parahaemolyticus has been reported to be an important pathogen for many aquatic
organisms, to our knowledge this might be the first report of early-immune
response in juvenile totoaba and these immune parameters may be reliable
indicators and can be useful in the health control of this species.
PMID- 27486684
TI - Origin of the Enhancement of the Second Hyperpolarizabilities of Metal-Carbon
Bonds.
AB - The spin-unrestricted coupled-cluster method was employed to investigate the
origin of the second hyperpolarizabilities (gamma) in model systems involving
metal-carbon bonds with various bond lengths as a function of their diradical
character (y) and charge transfer (CT). These systems exhibit unique features:
(i) sigma electrons give the dominant contribution to gamma, (ii) the pi
electrons contribution to gamma is negative, (iii) when the bond length
increases, gamma exhibits two positive extrema, which are associated with the CT
nature and the intermediate diradical character, respectively, (iv) and one
negative extremum corresponding to intermediate CT and diradical character, and
(v) in the bond stretching process, the maximum gamma amplitude per sigma bond is
about 7 times larger than that per pi bond. These features are significantly
different from those observed in pure organic systems.
PMID- 27486685
TI - An expanded framework for biomolecular visualization in the classroom: Learning
goals and competencies.
AB - A thorough understanding of the molecular biosciences requires the ability to
visualize and manipulate molecules in order to interpret results or to generate
hypotheses. While many instructors in biochemistry and molecular biology use
visual representations, few indicate that they explicitly teach visual literacy.
One reason is the need for a list of core content and competencies to guide a
more deliberate instruction in visual literacy. We offer here the second stage in
the development of one such resource for biomolecular three-dimensional visual
literacy. We present this work with the goal of building a community for online
resource development and use. In the first stage, overarching themes were
identified and submitted to the biosciences community for comment: atomic
geometry; alternate renderings; construction/annotation; het group recognition;
molecular dynamics; molecular interactions; monomer recognition;
symmetry/asymmetry recognition; structure-function relationships; structural
model skepticism; and topology and connectivity. Herein, the overarching themes
have been expanded to include a 12th theme (macromolecular assemblies), 27
learning goals, and more than 200 corresponding objectives, many of which cut
across multiple overarching themes. The learning goals and objectives offered
here provide educators with a framework on which to map the use of molecular
visualization in their classrooms. In addition, the framework may also be used by
biochemistry and molecular biology educators to identify gaps in coverage and
drive the creation of new activities to improve visual literacy. This work
represents the first attempt, to our knowledge, to catalog a comprehensive list
of explicit learning goals and objectives in visual literacy. (c) 2016 by The
International Union of Biochemistry and Molecular Biology, 45(1):69-75, 2017.
PMID- 27486688
TI - Spike gene deletion quasispecies in serum of patient with acute MERS-CoV
infection.
AB - The spike glycoprotein of the Middle East respiratory coronavirus (MERS-CoV)
facilitates receptor binding and cell entry. During investigation of a multi
facility outbreak of MERS-CoV in Taif, Saudi Arabia, we identified a mixed
population of wild-type and variant sequences with a large 530 nucleotide
deletion in the spike gene from the serum of one patient. The out of frame
deletion predicted loss of most of the S2 subunit of the spike protein leaving
the S1 subunit with an intact receptor binding domain. This finding documents
human infection with a novel genetic variant of MERS-CoV present as a
quasispecies. J. Med. Virol. 89:542-545, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27486689
TI - APS - Diagnostics and challenges for the future.
AB - Diagnosis of antiphospholipid syndrome (APS) is essentially based on the
detection of circulating antiphospholipid (aPL) antibodies. Progress have been
made on the standardization of tests exploring the presence of aPL as guidelines
on coagulation and immunological tests were recently published in the literature.
Clinical relevance of aPL profile has come from prospective cohort studies in
populations with a homogeneous antibody profile supporting the view that triple
positivity is a high risk pattern in patients and carriers. In addition to the
classic ones, several other tests have been proposed for the diagnosis of APS.
The detection of antibodies directed to domain 1 and 4/5 of beta2-Glycoprotein I
(beta2GP1) were found to be particularly sound. Several issues remain to be
addressed. We do not yet know what is the physiological function of beta2GP1 and
the pathophysiology of thrombosis and pregnancy loss in these patients. Moreover,
treatment is poorly defined especially in the case of feared catastrophic APS.
PMID- 27486687
TI - FBXW7 is involved in the acquisition of the malignant phenotype in epithelial
ovarian tumors.
AB - FBXW7 is a ubiquitin ligase that mediates ubiquitylation of oncoproteins, such as
c-Myc, cyclin E, Notch and c-Jun. FBXW7 is a known tumor-suppressor gene, and
mutations in FBXW7 have been reported in various human malignancies. In this
study, we examined the sequences of the FBXW7 and p53 genes in 57 ovarian cancer
clinical samples. Interestingly, we found no FBXW7 mutations associated with
amino acid changes. We also investigated FBXW7 expression levels in 126
epithelial ovarian tumors. FBXW7 expression was negatively correlated with the
malignant potential of ovarian tumors. That is to say, FBXW7 expression levels in
ovarian cancer samples were significantly lower than those in borderline and
benign tumors (P < 0.01). FBXW7 expression levels in serous carcinoma samples
were the lowest among four major histological subtypes. In addition, p53-mutated
ovarian cancer samples showed significantly lower levels of FBXW7 expression
compared with p53 wild-type cancer samples (P < 0.001). DNA methylation arrays
and bisulfite PCR sequencing experiments revealed that 5'-upstream regions of
FBXW7 gene in p53-mutated samples were significantly higher methylated compared
with those in p53 wild-type samples (P < 0.01). This data indicates that p53
mutations might suppress FBXW7 expression through DNA hypermethylation of FBXW7
5'-upstream regions. Thus, FBXW7 expression was downregulated in ovarian cancers,
and was associated with p53 mutations and the DNA methylation status of the 5'
upstream regions of FBXW7.
PMID- 27486686
TI - Quantitative Proteomic Analysis Reveals Similarities between Huntington's Disease
(HD) and Huntington's Disease-Like 2 (HDL2) Human Brains.
AB - The pathogenesis of HD and HDL2, similar progressive neurodegenerative disorders
caused by expansion mutations, remains incompletely understood. No systematic
quantitative proteomics studies, assessing global changes in HD or HDL2 human
brain, were reported. To address this deficit, we used a stable isotope labeling
based approach to quantify the changes in protein abundances in the cortex of 12
HD and 12 control cases and, separately, of 6 HDL2 and 6 control cases. The
quality of the tissues was assessed to minimize variability due to post mortem
autolysis. We applied a robust median sweep algorithm to quantify protein
abundance and performed statistical inference using moderated test statistics.
1211 proteins showed statistically significant fold changes between HD and
control tissues; the differences in selected proteins were verified by Western
blotting. Differentially abundant proteins were enriched in cellular pathways
previously implicated in HD, including Rho-mediated, actin cytoskeleton and
integrin signaling, mitochondrial dysfunction, endocytosis, axonal guidance,
DNA/RNA processing, and protein transport. The abundance of 717 proteins
significantly differed between control and HDL2 brain. Comparative analysis of
the disease-associated changes in the HD and HDL2 proteomes revealed that similar
pathways were altered, suggesting the commonality of pathogenesis between the two
disorders.
PMID- 27486690
TI - Proliferative Nodules vs Melanoma Arising in Giant Congenital Melanocytic Nevi
During Childhood.
AB - Importance: The differential diagnosis between proliferative nodules (PNs) and
melanoma arising in congenital melanocytic nevi (CMN) is crucial, as patients
with PNs most often experience no increased risk of melanoma with metastases and
death. Objective: To analyze the utility of immunohistochemistry and fluorescence
in situ hybridization (FISH) in distinguishing PNs from childhood and adult-onset
melanoma arising in CMN. Design, Setting, and Participants: A case series was
conducted from June 29, 1989, to November 12, 2009, of 13 children with PNs
arising in CMN in childhood and 5 children with melanomas arising in CMN in
childhood. Five patients with giant CMN with no nodules were included as negative
controls, and 6 patients with melanomas arising in CMN in adulthood were included
as positive controls. Follow-up ranged from 3 to 21 years in all children (mean,
9.9 years) and from 3 months to 7 years in adults. Specimens were selected for
immunohistochemistry and FISH. All histopathologic sections were reviewed by 2
dermatopathologists who examined all nodules arising at different ages in the
same patient and, in the case of melanoma, all locations. Data analysis was
performed from January 1, 2013, to January 31, 2015. Main Outcomes and Measures:
The ability to distinguish melanoma from PN using immunohistochemistry and/or
FISH. Results: Of the 13 patients (5 boys and 8 girls) with PNs present at birth,
all PNs were stable (mean follow-up, 9 years). Eight patients with PNs and 4 of 5
patients with childhood-onset melanoma showed homogeneous staining for HMB45,
while heterogeneous staining for HMB45 was seen in 3 of 6 patients with adult
onset melanoma. Expression of p16 was strongly positive in most patients with
childhood-onset PNs (10 of 11 patients) and melanoma (all patients) but negative
in 4 patients with adult-onset melanoma. Patients with PNs and the 5 patients
with childhood-onset melanoma had numerical chromosomal aberrations never
observed in the adjacent CMN. The 2 children with FISH-positive PNs are melanoma
free after 7 and 4 years. Only 1 patient with childhood-onset melanoma had a FISH
aberration compared with 4 patients with adult-onset melanoma. Conclusions and
Relevance: Immunohistochemistry and the 4-probe FISH melanoma analysis are not
useful for distinguishing PN from childhood-onset melanoma as opposed to adult
onset melanoma. Numerical anomalies seen in PNs but not in the adjacent CMN could
be the result of a chromosomal segregation malfunction resulting in the
development of nodules.
PMID- 27486691
TI - Phenolic content, antioxidant capacity and antimicrobial activity of leaf
extracts from Pistacia atlantica.
AB - The aim of this study was to investigate the secondary metabolites related to
Pistacia atlantica Desf as well as their biological activities. Results show that
using ethanol as a solvent exhibited the highest content of total phenolics and
flavonoids (68.23 mg GAE g-1 of DW and 44 mg RE g-1 of DW), followed by aqueous
one (20.07 mg GAE g-1 of DW and 15 mg RE g-1 of DW). Good correlation (Data not
shown) was obtained between the DPPH radical-scavenging activities and total
phenolics contents. Many similarities were observed between the results of the
DPPH (IC50 = 32 and 200 MUg mL-1) and ABTS (IC50 = 42 and 300 MUg mL-1) assays.
All tested extracts contained phenolic compounds exhibited an antimicrobial
effect against Gram-positive and Gram-negative bacteria. Further, researches for
identification and purification of phenolic compounds are required.
PMID- 27486692
TI - ?
PMID- 27486693
TI - ?
PMID- 27486694
TI - ?
PMID- 27486695
TI - Phage display as a tool to discover blood-brain barrier (BBB)-shuttle peptides:
panning against a human BBB cellular model.
AB - Most potential drugs for the treatment of central nervous system disorders do not
cross the blood-brain barrier (BBB). Much research effort has been devoted to the
discovery of new BBB-shuttle peptides-most of which have been identified by phage
display. Here we report for the first time on the use of phage display against a
human BBB cellular model which mimics the characteristics of the BBB. From the
panning experiment of a 12-mer library, the SGVYKVAYDWQH (SGV) peptide sequence
was selected and its permeability validated in the aforementioned model.
Furthermore, internalization studies suggested that SGV internalizes through a
clathrin-mediated mechanism and that it increases the uptake of a cargo in
endothelial cells. These results highlight the usefulness of in vitro BBB models
for the discovery of BBB-shuttle peptides through phage display libraries.
PMID- 27486696
TI - Optimizing Venous Thromboembolic Prophylaxis: Is Thromboelastography the Answer?
PMID- 27486697
TI - Polynanocrystalline Graphite: A New Carbon Anode with Superior Cycling
Performance for K-Ion Batteries.
AB - We synthesized a new type of carbon-polynanocrystalline graphite-by chemical
vapor deposition on a nanoporous graphenic carbon as an epitaxial template. This
carbon is composed of nanodomains being highly graphitic along c-axis and very
graphenic along ab plane directions, where the nanodomains are randomly packed to
form micron-sized particles, thus forming a polynanocrystalline structure. The
polynanocrystalline graphite is very unique, structurally different from low
dimensional nanocrystalline carbon materials, e.g., fullerenes, carbon nanotubes,
and graphene, nanoporous carbon, amorphous carbon and graphite, where it has a
relatively low specific surface area of 91 m2/g as well as a low Archimedes
density of 0.92 g/cm3. The structure is essentially hollow to a certain extent
with randomly arranged nanosized graphite building blocks. This novel structure
with disorder at nanometric scales but strict order at atomic scales enables
substantially superior long-term cycling life for K-ion storage as an anode,
where it exhibits 50% capacity retention over 240 cycles, whereas for graphite,
it is only 6% retention over 140 cycles.
PMID- 27486698
TI - Worse quality of life in young and recently diagnosed breast cancer survivors
compared with female survivors of other cancers: A cross-sectional study.
AB - Literature focusing on health-related quality of life (HRQoL) by cancer site
among women only is scarce. This study examines HRQoL of breast cancer (BC)
survivors compared with female survivors of other cancers, and to understand
which subgroups of BC survivors were particularly at risk of reduced HRQoL. We
placed emphasis on young (<50 years) and recently diagnosed (<=5 years)
survivors, where the deficits in HRQoL were most pronounced. The cross-sectional
study consisted of 2,224 BC survivors, 8,504 non-cancer controls and 2,205 other
cancer survivors in the Karma study. We examined HRQoL differences using linear
regression analyses in the whole cohort and in a subset of young and recently
diagnosed BC survivors (n = 242) and female survivors of other cancers (n = 140)
with comparable ages at diagnosis (43.6 vs 43.6, p = 0.917) and time since
diagnosis (2.3 vs 2.8 years, p < 0.001). HRQoL was assessed using the EORTC QLQ
C30 questionnaire. While only cognitive functioning was significantly compromised
in BC survivors compared with survivors of other cancers when women of all ages
were included, young BC survivors reported significantly lower HRQoL on multiple
functional scales (global quality of life, emotional, role, social and cognitive
functioning) and experienced more fatigue and insomnia. BC survivors with any
prior medical history of mental disorders reported poorer HRQoL than those
without such a history. We also observed a close-knit relationship between tumor
and treatment characteristics. BC survivors perform poorly in HRQoL in comparison
with female survivors of other cancers. Our results emphasize the importance of
age- and gender-appropriate comparison groups.
PMID- 27486700
TI - Addressing the stroke evidence-treatment gap.
PMID- 27486699
TI - Predicting unfolding thermodynamics and stable intermediates for alanine-rich
helical peptides with the aid of coarse-grained molecular simulation.
AB - This report focuses on the molecular-level processes and thermodynamics of
unfolding of a series of helical peptides using a coarse-grained (CG) molecular
model. The CG model was refined to capture thermodynamics and structural changes
as a function of temperature for a set of published peptide sequences. Circular
dichroism spectroscopy (CD) was used to experimentally monitor the temperature
dependent conformational changes and stability of published peptides and new
sequences introduced here. The model predictions were quantitatively or semi
quantitatively accurate in all cases. The simulations and CD results showed that,
as expected, in most cases the unfolding of helical peptides is well described by
a simply 2-state model, and conformational stability increased with increased
length of the helices. A notable exception in a 19-residue helix was when two Ala
residues were each replaced with Phe. This stabilized a partly unfolded
intermediate state via hydrophobic contacts, and also promoted aggregates at
higher peptide concentrations.
PMID- 27486701
TI - Effect of improved contact on reliability of sub-60 nm carbon nanotube vias.
AB - Advances in semiconductor technology due to the aggressive downward scaling of on
chip feature sizes have led to rapid rises in the resistivity and current density
of interconnect conductors. As a result, current interconnect materials, Cu and
W, are subject to performance and reliability constraints approaching or
exceeding their physical limits. Therefore, alternative materials are being
actively considered as potential replacements to meet such constraints. The
carbon nanotube (CNT) is among the leading replacement candidates for on-chip
interconnect vias due to its high aspect-ratio nanostructure and superior current
carrying capacity to Cu and W, as well as other potential candidates. Based on
the results for 40 nm and 60 nm top-contact metallized CNT vias, we demonstrate
that not only are their current-carrying capacities two orders of magnitude
higher than their Cu and W counterparts, they are enhanced by reduced via
resistance due to contact engineering facilitated by the first reported contact
resistance extraction scheme for a 40 nm linewidth.
PMID- 27486702
TI - Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in
infants.
AB - BACKGROUND: Bacterial meningitis poses diagnostic challenges in infants.
Antibiotic pretreatment and low bacterial density diminish cerebrospinal fluid
(CSF) culture yield, while laboratory parameters do not reliably identify
bacterial meningitis. Pro and anti-inflammatory cytokines are elevated in
bacterial meningitis and may be useful diagnostic adjuncts when CSF cultures are
negative. METHODS: In a prospective cohort study of infants, we used cytometric
bead arrays to measure tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL
1), IL-6, IL-8, IL-10, and IL-12 in CSF. Receiver operating characteristic (ROC)
analyses and Principal component analysis (PCA) were used to determine cytokine
combinations that identified bacterial meningitis. RESULTS: Six hundred and
eighty four infants < 6 mo were included; 11 had culture-proven bacterial
meningitis. IL-6 and IL-10 were the individual cytokines possessing greatest
accuracy in diagnosis of culture proven bacterial meningitis (ROC analyses; area
under the concentration-time curve (AUC) 0.91; 0.9103 respectively), and
performed as well as, or better than combinations identified using ROC and PCA.
CSF cytokines were highly correlated with each other and with CSF white blood
cell count (WBC) counts in infants with meningitis. A subset of antibiotic
pretreated culture-negative subjects demonstrated cytokine patterns similar to
culture positive subjects. CONCLUSION: CSF cytokine levels may aid diagnosis of
bacterial meningitis, and facilitate decision-making regarding treatment for
culture negative meningitis.
PMID- 27486703
TI - Altered Treg and cytokine responses in RSV-infected infants.
AB - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of
bronchiolitis and pneumonia in children under 1 y of age in the USA. The host
immune response is believed to contribute to RSV-induced disease. We hypothesize
that severe RSV infection in infants is mediated by insufficient regulation of
the host immune response of regulatory T cells (Tregs) resulting in
immunopathology. METHODS: Blood and nasal aspirates from 23 RSV-infected and 17
control infants under 1 y of age were collected. Treg frequencies were determined
by flow cytometry from peripheral blood mononuclear cells. Analysis of 24
cytokines was measured by multiplex assay on nasal aspirates. RESULTS: We
demonstrate that the frequency of activated Tregs is significantly reduced in the
peripheral blood of RSV-infected infants compared with age-matched controls.
Surprisingly, T helper (Th)17 related cytokines including interleukin (IL)-1beta,
IL-17A, and IL-23 were associated with a reduction in clinical symptoms of
respiratory distress. In addition, the amount of IL-33 protein in nasal washes, a
cytokine important in maintaining Treg homeostasis in mucosal tissues, was
decreased in RSV-infected children. CONCLUSION: These results suggest that
decreased Treg numbers and an inability to properly control the host inflammatory
response results in severe RSV infection.
PMID- 27486704
TI - Assessment of pedometer accuracy in capturing habitual types of physical
activities in overweight and obese children.
AB - BACKGROUND: Currently, there is a limited amount of research exploring physical
activity measurement tools in overweight and obese (OW/OB) children using
pedometers. Thus, our objective was to determine the accuracy of one spring
levered (SC-T2) and two piezoelectric pedometers (NL-1000 and Piezo) in OW/OB
children. METHODS: A total of 26 boys and 34 girls (n = 60) participated.
Pedometer step-counts were compared to observed step counts for walking (walking,
stair ascent and decent) and hopping tests. Pedometer accuracies were compared
with Friedman tests while Bland-Altman plots were used to establish the accuracy
of each pedometer against direct observations. RESULTS: Boys (n = 26) and females
(n = 34) were 96 and 91% OB, respectively. The two piezoelectric pedometers (NL
1000 and Piezo) were accurate for walking and stair climbing tasks, however all
pedometers were inaccurate for hopping tests. Averaged over all three walking
activities, the NL-1000 was the most accurate with 6.7% median error
(interquartile range (IQR): 0.0-13.3); followed by the Piezo with 10.0% median
error (IQR: 3.3-18.1); SC-T2 was the least accurate with -14.7% median error
(IQR: -54.8-3.5). CONCLUSION: These results support the use of the piezoelectric
pedometers for walking and stair climbing types of activities, which are typical
for OW/OB children in a nonlaboratory setting.
PMID- 27486705
TI - Colitis, independent of macronutrient intake, compromises bone structure and
strength in growing piglets.
AB - BACKGROUND: Deterioration in bone health is a concern in managing pediatric
inflammatory bowel diseases, but clear understanding of the independent
contributions of disease and nutrition is lacking. This study aimed to ascertain
whether bone health could be conserved during colitis by maintaining adequate
nutritional intake in growing piglets. METHODS: The effect of colitis on bone
structure and strength was determined in piglets with dextran sulphate sodium
induced colitis. Piglets received either 100% macro/micronutrient requirements or
50% macro/100% micronutrient requirements. Femurs were analyzed for dual-energy x
ray absorptiometry, peripheral quantitative computed tomography, microcomputed
tomography, and 3-point bending tests. RESULTS: Colitis, regardless of a well
nourished or malnourished diet, compromised areal bone mineral density (-17%) and
volumetric bone mineral density (-20%) in cortical and trabecular bone.
Structural integrity at mid-diaphysis was maintained during colitis; however,
lower cortical area, trabecular area, and bone mineral content resulted in lower
energy to break. CONCLUSION: Colitis compromises both bone structure and strength
of long bones in piglets, independent of macronutrient intakes. Although
confirmation of these findings in pediatric cohorts is needed, these data
identify aspects of bone health that may be affected by inflammatory bowel
disease.
PMID- 27486706
TI - Workplace wellness using online learning tools in a healthcare setting.
AB - The aim was to develop and evaluate an online learning tool for use with UK
healthcare employees, healthcare educators and healthcare students, to increase
knowledge of workplace wellness as an important public health issue. A 'Workplace
Wellness' e-learning tool was developed and peer-reviewed by 14 topic experts.
This focused on six key areas relating to workplace wellness: work-related
stress, musculoskeletal disorders, diet and nutrition, physical activity, smoking
and alcohol consumption. Each key area provided current evidence-based
information on causes and consequences, access to UK government reports and
national statistics, and guidance on actions that could be taken to improve
health within a workplace setting. 188 users (93.1% female, age 18-60) completed
online knowledge questionnaires before (n = 188) and after (n = 88) exposure to
the online learning tool. Baseline knowledge of workplace wellness was poor (n =
188; mean accuracy 47.6%, s.d. 11.94). Knowledge significantly improved from
baseline to post-intervention (mean accuracy = 77.5%, s.d. 13.71) (t(75) =
14.801, p < 0.0005) with knowledge increases evident for all included topics
areas. Usability evaluation showed that participants perceived the tool to be
useful (96.4%), engaging (73.8%) and would recommend it to others (86.9%).
Healthcare professionals, healthcare educators and pre-registered healthcare
students held positive attitudes towards online learning, indicating scope for
development of further online packages relating to other important health
parameters.
PMID- 27486707
TI - Care Transitions in Childhood Cancer Survivorship: Providers' Perspectives.
AB - PURPOSE: Most adolescent and young adult (AYA)-aged childhood cancer survivors
develop physical and/or psychosocial sequelae; however, many do not receive long
term follow-up (LTF) critical for screening, prevention, and treatment of late
effects. To develop a health services research agenda to optimize care models, we
conducted qualitative research with LTF providers examining existing models, and
successes and challenges in maintaining survivors' connections to care across
their transition to adulthood. METHODS: We interviewed 20 LTF experts (MDs, RNs,
social workers, education specialists, psychologists) from 10 Children's Oncology
Group-affiliated institutions, and analyzed data using grounded theory and
content analysis techniques. RESULTS: Participants described the complexity of
survivors' healthcare transitions. Survivors had pressing educational needs in
multiple domains, and imparting the need for prevention was challenging.
Multidisciplinary LTF teams focused on prevention and self-management. Care and
decisions about transfer were individualized based on survivors' health risks,
developmental issues, and family contexts. An interplay of provider and
institutional factors, some of which were potentially modifiable, also influenced
how transitions were managed. Interviewees rarely collaborated with community
primary care providers to comanage patients. Communication systems and collective
norms about sharing care limited comanagement capacity. Interviewees described
staffing practices, policies, and informal initiatives they found reduced
attrition. CONCLUSIONS: Results suggest that survivors will benefit from care
models that better connect patients, survivorship experts, and community
providers for uninterrupted LTF across transitions. We propose research
priorities, framing attrition from LTF as a public health concern, transition as
the central challenge in LTF, and transition readiness as a multilevel concept.
PMID- 27486708
TI - Screening of Toxic Effects of Bisphenol A and Products of Its Degradation:
Zebrafish (Danio rerio) Embryo Test and Molecular Docking.
AB - Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low
concentration. Degradation of BPA could lead to the formation of toxic products.
In this study, we compare the toxicity of BPA and seven intermediate products of
its degradation. The accuracy of three molecular docking programs (Surflex,
Autodock, and Autodock Vina) in predicting the binding affinities of selected
compounds to human (ERalpha, ERbeta, and ERRgamma) and zebrafish (ERalpha,
ERRgammaA, and ERRgammaB) estrogen and estrogen-related receptors was evaluated.
The docking experiments showed that 4-isopropylphenol could have similar toxicity
to that of BPA due to its high affinity to ERRgamma and ERRgammaB and high
octanol-water partitioning coefficient. The least toxic compounds were
hydroquinone and phenol. Those compounds as well as BPA were screened in the
zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic
effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA
caused the delay in development, multiple deformations, and low heartbeats (30
bps), whereas hydroquinone had no impact on the development of the zebrafish
embryo. Thus, the results of zebrafish screening are in good agreement with our
docking experiment. The molecular docking could be used to screen the toxicity of
other xenoestrogens and their products of degradation.
PMID- 27486709
TI - [Polonia Medyczna: struktura, wspolczesnosc i przyszlosc].
AB - It is estimated that approximately 20-25 000 polish physicians practice medicine
in different countries outside of Poland, enriching medical workforces in their
newly elected countries. The composition of this group, known as "Medical
Polonia", has been changing from post Second World War emigration, resulting from
the war and its political consequences, thru the next large wave of physicians
leaving the communist country in 1980's. The last large group of Polish
physicians has taken advantage of training opportunities or have started
practices in the European Union, having departed Poland permanently or
temporarily, after the country joined the European Union in 2004. The first
organizations of Polish physicians outside of Poland were founded almost
immediately after WWII in London, Chicago, New York, Paris, Lille, and later in
Stockholm. Decades later, re-invigorated by their native country gaining
independence after 1989, they organized the first World Congress of Medical
Polonia in 1991 (in collaboration with physicians' organization from Poland). The
World Federation of Polish Medical Organization Abroad was then established in
1994. Subsequently, many organizations joined the Federation, including several
from newly liberated countries of former Soviet Union. The Federation of Polish
Medical Organizations and its member societies actively promotes medical
education, collaboration between polish doctors all over the world, and the
exchange of ideas-sharing experiences with significant emphasis on the quality of
care and patient safety.
PMID- 27486710
TI - Genetics of Parkinson's disease: a review of SNCA and LRRK2.
AB - Parkinson's disease (PD) is a common neurodegenerative disorder that usually
affects the elderly. Resting tremor, rigidity, bradykinesia, and postural
instability are the main symptoms of PD. The loss of dopaminergic neurons in the
substantia nigra and Lewy bodies in remaining neurons are pathological
characteristics of PD. To combat these symptoms, dopaminergic therapy can benefit
PD patients; however, it is only symptomatic therapy. Although the pathogenesis
of PD has yet to be elucidated, approximately 10% of PD patients have familial
history of PD. Since the first discovery of a causative gene of PD, SNCA, in
1997, 18 other genes have been identified in familial PD. These discoveries make
it possible to begin to understand the pathogenesis of PD and can lead to the
development of curative therapies. Here, we describe the clinical and
pathological features of PD caused by mutations in two major PD-associated genes,
SNCA and LRRK2. Mutations in SNCA revealed the pathological association between
alpha-synuclein and PD, while LRRK2 is the most common genetic cause of PD. The
patients with LRRK2 mutations present with relatively typical PD phenotypes, but
heterogeneous pathologies including alpha-synuclein, tau, and occasionaly
transactive response DNA-binding protein 43.
PMID- 27486711
TI - [Dehumanizacja wspolczesnej medycyny: przyczyny i przeciwdzialanie].
AB - A discussion of causes of dehumanisation in contemporary medicine and possible
methods of preventing this situation. The causes can be divided into external,
associated with the influence of the environment of civilisation, and internal,
which constitute a form of aunwanted side effects" of the rapid progress of
civilisation. The latter include reductionist thinking and axiological neutrality
typical of natural sciences, increased import_ance of technology, and excessive
specialisation combined with poor coordination of diagnostic work-up and
treatment or the lack of such coordination. Possible preventive measures include
a change in the model of medical education, consisting for instance in the
inclusion of humanistic elements and a more holistic view of the patient, as well
as a change in the health care model so that the diagnostic work-up and treatment
would be coordinated mainly by the primary health care doctor.
PMID- 27486712
TI - [Masywne krwawienie z jelita malego: nowa opcja terapeutyczna z lokalizacja
microcoil i laparoskopowa resekcja].
AB - Masywne krwawienie z przewodu pokarmowego prezentuje kompleksowy problem
diagnostyczny i terapeutyczny. Dokladna identyfikacja miejsca krwawienia jest
skomplikowana i chirurgiczna resekcja miejsca krwawienia jest trudne. Angiografii
uzywanej do lokalizacji i embolizacji miejscu krwawienia w krazeniu krezkowym
brakuje skutecznosci ze wzgledu na skomplikowana siec zespolenia naczyn
krwionosnych zaopatrujacych jelito cienkie. Przedoperacyjnie umieszczenie
microcoil dla fluoroskopowo kierowanej laparoskopowej resekcji jelita cienkiego
zostalo wykorzystane w przypadku 58-letniej kobiety leczonej chemioterapia z
uzyciem idarubicyny i cytarabiny. Pacjentka miala krwawienie z przewodu
pokarmowego, ktore nie reagowalo na leczenie zachowawcze i wymagalo masywnych
transfuzji produktow krwi.
PMID- 27486713
TI - [Laryngotracheitis, recurrent laryngotracheitis and asthma in children: features
of ontogenesis and feeding in the first months of life].
AB - Objective of research was to study features of ontogenesis and feeding in the
first months of life in children with laryngotracheitis (LT), recurrent
laryngotracheitis (RLT) and asthma. METHODS: Questionnaire-based survey was
performed to collect data on anamnesis of 1004 children aged 6-14 years (575
children with a history of LT, 60 children with asthma, and 369 children of
control group) pertaining to preeclampsia in mothers, history of birth asphyxia,
preterm birth and feeding during the first months of life in children. Children
with LT were divided into two groups: 458 children with 1-3 episodes of LT and
117 children with RLT (4 or more episodes of LT). RESULTS: The frequency of
preeclampsia among mothers of children with RLT exceeded the corresponding
frequency among mothers of children with 1-3 episodes of LT and children of
control group in 2.1 and 2.8 times, respectively. The frequency of birth asphyxia
or preterm birth among children with RLT exceeded the corresponding frequency
among children with 1-3 episodes of LT and children of control group by a factor
of 2. The frequency of breastfeeding initiation after 24 hours of birth among
children with asthma or RLT exceeded the corresponding frequency among children
with 1-3 episodes of LT (in 1.4 and 1.5 times, respectively) and among children
of control group (in 2.4 and 2.6 times, respectively). CONCLUSION: The frequency
of preeclampsia in mothers, birth asphyxia, preterm birth and late initiation of
breastfeeding among children with RLT exceeded the corresponding frequency among
children with 1-3 episodes of LT and children of control group. There was no
significant difference between the frequency of preeclampsia in mothers, birth
asphyxia, initiation of breastfeeding among children with RLT and children with
asthma. Formula feeding in the first months of life was equally often observed
among children with LT, RLT and asthma and significantly exceeded the
corresponding percentage among children in control group.
PMID- 27486714
TI - [Jak obnizyc umieralnosc kobiet z powodu krwotokow poporodowych?].
AB - Postpartum hemorrhage (PPH) is still a common obstetrical complication and is
believed to be the leading cause of peripartum maternal mortality in Poland. PPH
prevention is though the main aim of contemporary obstetrics. It might be
obtained by careful screening for high risk of PPH gravidas and active management
of the third stage of labor. Postpartum hemorrhage requires aggressive measures,
accurate diagnosis and precise management. The knowledge of algorithms of PPH
management is essential and required for all physicians working in the Delivery
Room.
PMID- 27486715
TI - Why parents refuse immunization?
AB - Rates of child immunization are falling in many countries, leading to the
increase of morbidity and mortality from diseases controlled by vaccinations. The
simplified model of the natural history of immunization follows a sequence of
fear of the disease before vaccination, followed by acceptance of the vaccination
until plateau, where the population forgets the morbidity and mortality of pre
immunization. Historical factors including withdrawals of vaccines, and
publications regarding the true or falsified dangers of vaccines still resonate
with parents. Building on these historical factors, unscientific sources such as
naturopaths, homeopaths, chiropractors, celebrities and lay-people with anecdotal
evidence and even scientific sources such as some universities and some medical
doctors push their views on anti-vaccination, which proves to make the decision
to vaccinate more difficult on parents. The main reason that parents refuse
vaccination is a desire to protect their children. These parents believe that
vaccination is harmful, or that not vaccinated children are healthier than
vaccinated children. Scientific data often will lose with pseudoscientific, false
or anecdotal data that have higher sensational and emotional impact on parents.
With so many sources giving so many factors which sometimes contradict
themselves, it is indeed difficult for a parent to make a clear decision for
their child.
PMID- 27486716
TI - An investigation of the auditory perception of western lowland gorillas in an
enrichment study.
AB - Previous research has highlighted the varied effects of auditory enrichment on
different captive animals. This study investigated how manipulating musical
components can influence the behavior of a group of captive western lowland
gorillas (Gorilla gorilla gorilla) at Bristol Zoo. The gorillas were observed
during exposure to classical music, rock-and-roll music, and rainforest sounds.
The two music conditions were modified to create five further conditions:
unmanipulated, decreased pitch, increased pitch, decreased tempo, and increased
tempo. We compared the prevalence of activity, anxiety, and social behaviors
between the standard conditions. We also compared the prevalence of each of these
behaviors across the manipulated conditions of each type of music independently
and collectively. Control observations with no sound exposure were regularly
scheduled between the observations of the 12 auditory conditions. The results
suggest that naturalistic rainforest sounds had no influence on the anxiety of
captive gorillas, contrary to past research. The tempo of music appears to be
significantly associated with activity levels among this group, and social
behavior may be affected by pitch. Low tempo music also may be effective at
reducing anxiety behavior in captive gorillas. Regulated auditory enrichment may
provide effective means of calming gorillas, or for facilitating active behavior.
Zoo Biol. 35:398-408, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27486717
TI - The Influence of Zeolites on Radical Formation During Lignin Pyrolysis.
AB - Lignin from lignocellulosic biomass is a promising source of energy, fuels, and
chemicals. The conversion of the polymeric lignin to fuels and chemicals can be
achieved by catalytic and noncatalytic pyrolysis. The influence of nonporous
silica and zeolite catalysts, such as silicalite, HZSM5, and HUSY, on the radical
and volatile product formation during lignin pyrolysis was studied by in situ
high-temperature electron paramagnetic resonance spectroscopy (HTEPR) as well as
GC-MS. Higher radical concentrations were observed in the samples containing
zeolite compared to the sample containing only lignin, which suggests that there
is a stabilizing effect by the inorganic surfaces on the formed radical
fragments. This effect was observed for nonporous silica as well as for HUSY,
HZSM5, and silicalite zeolite catalysts. However, the effect is far larger for
the zeolites owing to their higher specific surface area. The zeolites also
showed an effect on the volatile product yield and the product distribution
within the volatile phase. Although silicalite showed no effect on the product
selectivity, the acidic zeolites such as HZSM5 or HUSY increased the formation of
deoxygenated products such as benzene, toluene, xylene (BTX), and naphthalene.
PMID- 27486718
TI - Preventing recurrence of diffuse malignant peritoneal mesothelioma.
AB - INTRODUCTION: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive
malignancy with a poor prognosis when treated with systemic therapy.
Cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) is considered
the best therapy in DMPM, but a high risk of locoregional recurrence remains.
AREAS COVERED: This review describes patient selection and operative goals with
CRS and IPC, the reported outcomes with this approach, and the data supporting
platinum-based IPC. We assess the pharmacokinetics supporting the use of dwell
IPC. We outline clinical, imaging and laboratory surveillance for recurrence. In
addition, we highlight the role of re-operation, both as a planned second
procedure and in the context of disease recurrence. Literature review was
performed via Medline search. Expert commentary: CRS/IPC offers survival benefit
in selected patients with DMPM, but given the high rate of recurrence, close
surveillance is needed post-operatively. Strategies to prevent and treat
recurrent disease include dwell IPC and second CRS/IPC.
PMID- 27486719
TI - Nursing students' spiritual talks with patients - evaluation of a partnership
learning programme in clinical practice.
AB - AIMS AND OBJECTIVES: To evaluate the impact of a partnership learning programme
designed to support undergraduate nursing students' competence in speaking with
patients about spiritual issues. BACKGROUND: Spiritual care is an oft-neglected
and underexposed area of nursing practice. Despite the increasing amount of
research on spiritual care in educational programmes, little is known about
nursing students' experiences with existential/spiritual talks and the process of
learning about spiritual care in the clinical placement. DESIGN: The project used
a qualitative evaluation design to evaluate the impact of a partnership-initiated
intervention focusing on student learning of spiritual care in a hospital ward.
METHODS: Data were collected through three focus group interviews with bachelor
of nursing students from one Norwegian university college and supplemented with
notes. Data were analysed by means of qualitative interpretative content
analysis. RESULTS: The intervention was found to enhance students' competence in
spiritual talks. The students developed an extended understanding of
spirituality, became more confident in speaking with patients about spiritual
issues and more active in grasping opportunities to provide spiritual care.
Participating nurses significantly contributed to the students' learning process
by being role models, mentoring the students and challenging them to overcome
barriers in speaking with patients about spiritual issues. CONCLUSIONS: The
partnership learning programme proved to be a useful model in terms of enhancing
students' confidence in speaking with patients about spiritual concerns.
RELEVANCE TO CLINICAL PRACTICE: Collaboration between nursing university colleges
and clinical placements could help nursing students and clinical nurses to
develop competencies in spiritual care and bridge the gap between academic
education and clinical education, to the benefit of both.
PMID- 27486720
TI - The Biological Basis for Nonunions.
AB - Fracture nonunion is a failure of the biological processes of fracture-healing.
Critical cellular events in fracture-healing include the inflammatory response,
differentiation and proliferation of progenitor cells, formation of
fibrocartilage callus, angiogenesis and subsequent mineralization of the callus,
vascular union (restoration of normal medullary circulation), and conversion of
woven bone to lamellar bone. All critical events are closely regulated and
coordinated by numerous cytokines and growth factors, which are expressed in
complex spatial and temporal patterns throughout the repair process. At all
phases of fracture-healing, poor cellular and metabolic capacity (e.g., chronic
disease), excessive instability, and poor vascularity inhibit cellular responses
and healing. Many biological treatments to prevent or treat nonunions are
emerging in clinical use, including stem-cell and bone-marrow-aspirate
preparations, various progenitor cells and growth factors (e.g., recombinant
human bone morphogenetic proteins), and gene therapy.
PMID- 27486721
TI - Current Controversies in Reverse Total Shoulder Arthroplasty.
AB - Reverse total shoulder arthroplasty can restore forward elevation in
pseudoparalytic shoulders, can reduce pain, and can increase quality of life for
patients; however, there are a number of issues with regard to the design and
ideal implantation technique of reverse total shoulder arthroplasties that remain
controversial. Glenospheres with a Grammont, medialized center of rotation and
designs with a more lateralized center of rotation have specific pros and cons.
Medialized designs have historically decreased glenosphere loosening but increase
scapular notching, and lateralized designs decrease notching and improve range of
motion but historically have resulted in increased baseplate failure. As such, a
concrete conclusion with regard to medialization or lateralization of the
glenosphere cannot be made at this time. Caudal, inferior placement of the
glenosphere increases internal rotation, external rotation, abduction, and
adduction while reducing notching. Superior baseplate positioning and tilt are
correlated with baseplate failure and therefore should be avoided. It remains
unclear whether neutral or slightly inferior tilt is preferred. The ideal
humerosocket inclination angle remains unclear. The 135[degrees] designs appear
to have a lower rate of scapular notching than the Grammont-style 155[degrees]
humerosockets. The implications of this angle for instability remain unclear as,
to our knowledge, there have been no randomized comparisons and the largest meta
analysis was confounded by other implant variables.
PMID- 27486722
TI - Biological Treatments for Tendon and Ligament Abnormalities: A Critical Analysis
Review.
AB - The poor intrinsic healing potential of tendon and ligamentous tissue has driven
the search for biological agents that can improve healing, most notably platelet
rich plasma (PRP) and autologous stem cells. Current evidence best supports the
use of PRP as treatment for chronic, degenerative tendinopathies such as lateral
epicondylitis of the elbow or patellar tendinopathy. It does not support the use
of PRP to promote tendon or ligament-to-bone healing in rotator cuff repair or
anterior cruciate ligament (ACL) reconstruction. Clinical evidence regarding the
use of autologous stem cells as treatment for tendon and ligament abnormalities
is currently limited. However, the initial results appear to be promising,
particularly following rotator cuff repair. A major limitation in the evaluation
of current data is the lack of standardization in the preparation and composition
of PRP, which are often not reported. Future investigators should make an effort
to report the method of preparation and final composition of PRP used. Autologous
stem cells were most often harvested from bone marrow aspirate but were
occasionally derived from dermal tenocyte cells. Recent studies have explored new
sources for stem cells, including adipose tissue, peripheral blood, and human
amniotic tissue. We expect that clinical data evaluating these treatments will
soon emerge.
PMID- 27486723
TI - Instrumented Gait Analysis: A Tool in the Treatment of Spastic Gait Dysfunction.
AB - Spasticity is a term commonly used to describe a collection of muscle
overactivity patterns associated with the upper motor neuron syndrome including
actual spasticity, clonus, dystonia, co-contraction, associated reactions, and
flexor or extensor spasms. Gait dysfunction in the upper motor neuron syndrome
can be due to a combination of paresis, impaired coordination and balance, and
muscle overactivity and contracture. Treatment options include physiotherapy,
assistive devices, orthotic devices, oral and intrathecal medications,
intramuscular chemodenervation, neurolysis, and/or neuro-orthopaedic surgical
procedures. The objective evaluation of walking and its underlying muscle
activation patterns can be performed by the simultaneous collection of joint
kinematics, kinetics, and dynamic electromyography (EMG) data that serve as an
extension of the physical examination to better discern primary gait deviations
from compensatory gait deviations as well as underlying muscle overactivity from
contracture. Despite the science behind instrumented three-dimensional gait
analysis, its specific contribution to clinical and surgical decision-making is
not well utilized because of its associated cost, the incorrect view by some
insurance companies of gait analysis being a research technique, the dearth of
qualified clinical gait and motion analysis laboratories accessible to adult
patients, and limited access to orthopaedic surgeons who have experience in the
treatment of neurological disorders for this patient population.
PMID- 27486724
TI - Endoscopic Compared with Open Operative Treatment of Carpal Tunnel Syndrome.
AB - Carpal tunnel syndrome is the most common peripheral nerve compression syndrome.
Treatment options include wrist-neutral bracing, corticosteroid injections,
operative release of the transverse carpal ligament, and symptom-relief options.
Endoscopic carpal tunnel release may give patients a faster recovery compared
with traditional open release, but there are no ultimate differences in outcome
among the various surgical options.
PMID- 27486725
TI - Microfracture of Articular Cartilage.
AB - Microfracture is a treatment option for symptomatic, full-thickness cartilage
defects. Microfracture is most likely to be successful when performed in nonobese
patients under the age of thirty years for small (<2 to 4-cm2) femoral condylar
defects that have been symptomatic for a short time (less than twelve to twenty
four months). Microfracture has acceptable short-term clinical results, but
results can be expected to decline over time. Long-term studies that compare
microfracture with advanced cartilage restoration techniques are required to
ascertain whether these newer techniques provide longer-lasting results.
PMID- 27486726
TI - Variability in Response to Bilateral Medial Rectus Recessions in Infantile
Esotropia.
AB - PURPOSE: To evaluate factors associated with surgical success in bilateral medial
rectus recessions in infantile esotropia. METHODS: The results of 97 patients
with infantile esotropia undergoing surgical correction from January 2010 through
December 2013 at Children's Medical Center of Dallas were reviewed. Multivariate
logistic regression analysis of risk factors for success and evaluation of the
relationship of surgical responses to baseline characteristics were performed.
RESULTS: The authors achieved an overall success rate of 59% (57 of 97 patients)
with one surgery. At the time of surgery, preoperative angle, refraction,
amblyopia, and simultaneous inferior oblique surgery were not significantly
related to success or failure. The mean dose response was 3.61 +/- 1.45 prism
diopters per millimeter of surgery and was modestly correlated only with the
preoperative deviation (r(2) = 0.32). Failure was associated with variability in
dose-response, not inadequate or inconsistent with surgical dosing. CONCLUSIONS:
Surgical success with bilateral medial rectus recessions in infantile esotropia
is limited by the high variability in surgical dose-response. [J Pediatr
Ophthalmol Strabismus. 2016;53(5):305-310.].
PMID- 27486727
TI - Congenital Nasolacrimal Duct Obstruction: Comparison of Two Different Treatment
Algorithms.
AB - PURPOSE: To clarify the most appropriate treatment regimen for congenital
nasolacrimal duct obstruction (CNLDO). METHODS: A retrospective observational
analysis was performed of patients undergoing probing with or without intubation
to treat CNLDO in a single institution (Royal Victoria Hospital, Belfast) from
2006 to 2011. RESULTS: Based on exclusion criteria, 246 eyes of 177 patients
(aged 0 to 9.8 years with a mean age of 2.1 years) were included in this study:
187 (76%) eyes had successful outcome at first intervention with primary probing,
whereas 56 (23%) eyes underwent secondary intervention. There were no significant
differences by gender, age, or obstruction complexity between the successful and
unsuccessful patients with first intervention. For those patients requiring
secondary intervention, 16 of 24 (67%) eyes had successful probing, whereas 22 of
24 (92%) had successful intubation. Patients with intubation as a secondary
procedure were significantly more likely to have a successful outcome (P = .037).
Statistical analysis was performed using the Fisher's exact test and Barnard's
exact test. CONCLUSIONS: Primary probing for CNLDO has a high success rate that
is not adversely affected by increasing age. This study also indicates that if
initial probing is unsuccessful, nasolacrimal intubation rather than repeat
probing yields a significantly higher success rate. [J Pediatr Ophthalmol
Strabismus. 2016;53(5):285-291.].
PMID- 27486728
TI - Retinoblastoma Control With Primary Intra-arterial Chemotherapy: Outcomes Before
and During the Intravitreal Chemotherapy Era.
AB - PURPOSE: To compare outcomes of intra-arterial chemotherapy for retinoblastoma as
primary therapy before (Era I) and during (Era II) the intravitreal chemotherapy
era. METHODS: In this retrospective interventional case series at a tertiary
referral center, 66 eyes of 66 patients with untreated unilateral retinoblastoma
were used. intraarterial chemotherapy into the ophthalmic artery under
fluoroscopic guidance was performed using melphalan in every case, with
additional topotecan as necessary. Intravitreal chemotherapy using melphalan
and/or topotecan was employed as needed for active vitreous seeding. Globe
salvage was measured based on the International Classification of Retinoblastoma
(ICRB) during two eras. RESULTS: The two eras encompassed 2008 to 2012
(intraarterial chemotherapy alone, Era I) and 2012 to 2015 (intraarterial
chemotherapy plus intravitreal chemotherapy, Era II). Over this period, there
were 66 patients with unilateral untreated retinoblastoma treated with primary
intra-arterial chemotherapy. A comparison of features (Era I vs Era II) revealed
no significant difference in mean patient age (24 vs 24 months), ICRB groups,
mean largest tumor diameter (19 vs 17 mm), mean largest tumor thickness (10 vs 10
mm), vitreous seed presence (56% vs 59%), subretinal seed presence (67% vs 62%),
retinal detachment (70% vs 66%), or vitreous hemorrhage (0% vs 5%). There was no
significant difference in mean number of intra-arterial chemotherapy cycles (3 vs
3.1) or intraarterial chemotherapy dosages. Following therapy, there was a
significant difference (Era I vs Era II) in the need for enucleation overall (44%
vs 15%, P = .012), especially for group E eyes (75% vs 27%, P = .039). Four of
the eyes that initiated therapy in Era I later required intravitreal chemotherapy
during Era II. The enucleation rate was 0% for groups B and C in both eras and
non-significant for group D (23% vs 13%). There were no patients with stroke,
seizure, limb ischemia, extraocular tumor extension, secondary leukemia,
metastasis, or death. CONCLUSIONS: The current era of retinoblastoma management
using intra-arterial chemotherapy plus additional intravitreal chemotherapy (as
needed for vitreous seeding) has improved globe salvage in eyes with advanced
retinoblastoma. [J Pediatr Ophthalmol Strabismus. 2016;53(5):275-284.].
PMID- 27486729
TI - The Effectiveness of a Mobile Clinic in Improving Follow-up Eye Care for At-Risk
Children.
AB - PURPOSE: To investigate the potential of a mobile ophthalmic unit in the
schoolyard to improve the follow-up rate for children who have failed an
optometric in-school screening program. Previously, the optometric program made
referrals to the center and only 53% of students attended the desired
ophthalmology consultation. METHODS: This was a cohort study of students
conducted in elementary school lots in socioeconomically disadvantaged
communities. The mobile ophthalmic unit visited schools where students with
parental consent who needed examination had been identified by an in-school
optometric vision care program. RESULTS: A total of 132 students were referred by
the optometric program, of whom 95 (72%) had complete signed consent forms.
Eighty-two patients (62%, confidence interval: 54% to 70%) were successfully seen
by the mobile unit. Compared to the historical rate of successful completion of
ophthalmology consultation (53%), a statistically significant improvement in
follow-up was noted (P = .036). On a Likert scale of 1 to 5, the mean school
nurse satisfaction rating was 4.8. CONCLUSIONS: The findings demonstrate the
potential impact of mobile eye clinics at schools in connecting children with
ophthalmic care. [J Pediatr Ophthalmol Strabismus. 2016;53(6):344-348.].
PMID- 27486730
TI - Respiratory Viral Infections.
PMID- 27486731
TI - Human Influenza Virus Infections.
AB - Seasonal and pandemic influenza are the two faces of respiratory infections
caused by influenza viruses in humans. As seasonal influenza occurs on an annual
basis, the circulating virus strains are closely monitored and a yearly updated
vaccination is provided, especially to identified risk populations. Nonetheless,
influenza virus infection may result in pneumonia and acute respiratory failure,
frequently complicated by bacterial coinfection. Pandemics are, in contrary,
unexpected rare events related to the emergence of a reassorted human-pathogenic
influenza A virus (IAV) strains that often causes increased morbidity and spreads
extremely rapidly in the immunologically naive human population, with huge
clinical and economic impact. Accordingly, particular efforts are made to advance
our knowledge on the disease biology and pathology and recent studies have
brought new insights into IAV adaptation mechanisms to the human host, as well as
into the key players in disease pathogenesis on the host side. Current antiviral
strategies are only efficient at the early stages of the disease and are
challenged by the genomic instability of the virus, highlighting the need for
novel antiviral therapies targeting the pulmonary host response to improve viral
clearance, reduce the risk of bacterial coinfection, and prevent or attenuate
acute lung injury. This review article summarizes our current knowledge on the
molecular basis of influenza infection and disease progression, the key players
in pathogenesis driving severe disease and progression to lung failure, as well
as available and envisioned prevention and treatment strategies against influenza
virus infection.
PMID- 27486732
TI - Avian Influenza A Viruses: Evolution and Zoonotic Infection.
AB - Although efficient human-to-human transmission of avian influenza virus has yet
to be seen, in the past two decades avian-to-human transmission of influenza A
viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused
human infections associated with high mortality, and since 1998 the virus has
evolved into many clades of variants with significant antigenic diversity. In
2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs)
breached the animal-human host species barrier in Asia. In humans, roughly 35% of
A/H7N9-infected patients succumbed to the zoonotic infection, and two of three
A/H10N8 human infections were also lethal; however, neither of these viruses
cause influenza-like symptoms in poultry. While most of these cases were
associated with direct contact with infected poultry, some involved sustained
human-to-human transmission. Thus, these events elicited concern regarding
potential AIV pandemics. This article reviews the human incursions associated
with AIV variants and the potential role of pigs as an intermediate host that may
hasten AIV evolution. In addition, we discuss the known influenza A virus
virulence and transmission factors and their evaluation in animal models. With
the growing number of human AIV infections, constant vigilance for the emergence
of novel viruses is of utmost importance. In addition, careful characterization
and pathobiological assessment of these novel variants will help to identify
strains of particular concern for future pandemics.
PMID- 27486733
TI - Metapneumovirus Infections and Respiratory Complications.
AB - Acute respiratory tract infections (ARTIs) are the most common illnesses
experienced by people of all ages worldwide. In 2001, a new respiratory pathogen
called human metapneumovirus (hMPV) was identified in respiratory secretions.
hMPV is an RNA virus of the Paramyxoviridae family, and it has been isolated on
every continent and from individuals of all ages. hMPV causes 7 to 19% of all
cases of ARTIs in both hospitalized and outpatient children, and the rate of
detection in adults is approximately 3%. Symptoms of hMPV infection range from a
mild cold to a severe disease requiring a ventilator and cardiovascular support.
The main risk factors for severe disease upon hMPV infection are the presence of
a high viral load, coinfection with other agents (especially human respiratory
syncytial virus), being between 0 and 5 months old or older than 65 years, and
immunodeficiency. Currently, available treatments for hMPV infections are only
supportive, and antiviral drugs are employed in cases of severe disease as a last
resort. Ribavirin and immunoglobulins have been used in some patients, but the
real efficacy of these treatments is unclear. At present, the direction of
research on therapy for hMPV infection is toward the development of new
approaches, and a variety of vaccination strategies are being explored and tested
in animal models. However, further studies are required to define the best
treatment and prevention strategies.
PMID- 27486734
TI - Human Respiratory Syncytial Virus: Infection and Pathology.
AB - The human respiratory syncytial virus (hRSV) is by far the major cause of acute
lower respiratory tract infections (ALRTIs) worldwide in infants and children
younger than 2 years. The overwhelming number of hospitalizations due to hRSV
induced ALRTI each year is due, at least in part, to the lack of licensed
vaccines against this virus. Thus, hRSV infection is considered a major public
health problem and economic burden in most countries. The lung pathology
developed in hRSV-infected individuals is characterized by an exacerbated
proinflammatory and unbalanced Th2-type immune response. In addition to the
adverse effects in airway tissues, hRSV infection can also cause neurologic
manifestations in the host, such as seizures and encephalopathy. Although the
origins of these extrapulmonary symptoms remain unclear, studies with patients
suffering from neurological alterations suggest an involvement of the
inflammatory response against hRSV. Furthermore, hRSV has evolved numerous
mechanisms to modulate and evade the immune response in the host. Several studies
have focused on elucidating the interactions between hRSV virulence factors and
the host immune system, to rationally design new vaccines and therapies against
this virus. Here, we discuss about the infection, pathology, and immune response
triggered by hRSV in the host.
PMID- 27486735
TI - Parainfluenza Virus Infection.
AB - Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of
the Paramyoviridaie family. There are four serotypes which cause respiratory
illnesses in children and adults. HPIVs bind and replicate in the ciliated
epithelial cells of the upper and lower respiratory tract and the extent of the
infection correlates with the location involved. Seasonal HPIV epidemics result
in a significant burden of disease in children and account for 40% of pediatric
hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup
cases. Parainfluenza viruses are associated with a wide spectrum of illnesses
which include otitis media, pharyngitis, conjunctivitis, croup,
tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include
apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely
disseminated infection. Immunity resulting from disease in childhood is
incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in
adults. Severe disease and fatal pneumonia may occur in elderly and
immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell
transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6
months. Though sensitive molecular diagnostics are available to rapidly diagnose
HPIV infection, effective antiviral therapies are not available. Currently,
treatment for HPIV infection is supportive with the exception of croup where the
use of corticosteroids has been found to be beneficial. Several novel drugs
including DAS181 appear promising in efforts to treat severe disease in
immunocompromised patients, and vaccines to decrease the burden of disease in
young children are in development.
PMID- 27486736
TI - Update on Human Rhinovirus and Coronavirus Infections.
AB - Human rhinovirus (HRV) and coronavirus (HCoV) infections are associated with both
upper respiratory tract illness ("the common cold") and lower respiratory tract
illness (pneumonia). New species of HRVs and HCoVs have been diagnosed in the
past decade. More sensitive diagnostic tests such as reverse transcription
polymerase chain reaction have expanded our understanding of the role these
viruses play in both immunocompetent and immunosuppressed hosts. Recent
identification of severe acute respiratory syndrome and Middle East respiratory
syndrome viruses causing serious respiratory illnesses has led to renewed efforts
for vaccine development. The role these viruses play in patients with chronic
lung disease such as asthma makes the search for antiviral agents of increased
importance.
PMID- 27486737
TI - Middle East Respiratory Syndrome Virus Pathogenesis.
AB - Coronaviruses (CoVs) are enveloped RNA viruses that infect birds, mammals, and
humans. Infections caused by human coronaviruses (hCoVs) are mostly associated
with the respiratory, enteric, and nervous systems. The hCoVs only occasionally
induce lower respiratory tract disease, including bronchitis, bronchiolitis, and
pneumonia. In 2002 to 2003, a global outbreak of severe acute respiratory
syndrome (SARS) was the seminal detection of a novel CoV (SARS-CoV). A decade
later (June 2012), another novel CoV was implicated as the cause of Middle East
respiratory syndrome (MERS) in Saudi Arabia. Although bats might serve as a
reservoir of MERS-CoV, it is unlikely that they are the direct source for most
human cases. Severe lines of evidence suggest that dromedary camels have been the
major cause of transmission to humans. The emergence of MERS-CoV has triggered
serious concerns about the potential for a widespread outbreak. All MERS cases
were linked directly or indirectly to the Middle East region including Saudi
Arabia, Jordan, Qatar, Oman, Kuwait, and UAE. MERS cases have also been reported
in the later phases in the United Kingdom, France, Germany, Italy, Spain, and
Tunisia. Most of these MERS cases were linked with the Middle East. The high
mortality rates in family-based and hospital-based outbreaks were reported among
patients with comorbidities such as diabetes and renal failure. MERS-CoV causes
an acute, highly lethal pneumonia and renal dysfunction. The major complications
reported in fatal cases are hyperkalemia with associated ventricular tachycardia,
disseminated intravascular coagulation, pericarditis, and multiorgan failure. The
case-fatality rate seems to be higher for MERS-CoV (around 30%) than for SARS-CoV
(9.6%). The combination regimen of type 1 interferon + lopinavir/ritonavir is
considered as the first-line therapy for MERS. Antiviral treatment is generally
recommended for 10 to 14 days in patients with MERS-CoV infection. Convalescent
plasma therapy has shown some efficacy among patients refractory to antiviral
drugs if administered within 2 weeks of the onset of the disease.
PMID- 27486738
TI - Enterovirus D68 and Human Respiratory Infections.
AB - Enterovirus D68 (EV-D68) is a member of the species Enterovirus D in the genus
Enterovirus of the Picornaviridae family. EV-D68 was first isolated in the United
States in 1962 and is primarily an agent of respiratory disease. Infections with
EV-D68 have been rarely reported until recently, when reports of EV-D68
associated with respiratory disease increased notably worldwide. An outbreak in
2014 in the United States, for example, involved more than 1,000 cases of severe
respiratory disease that occurred across almost all states. Phylogenetic analysis
of all EV-D68 sequences indicates that the circulating strains of EV-D68 can be
classified into two lineages, lineage 1 and lineage 2. In contrast to the
prototype Fermon strain, all circulating strains have deletions in their genomes.
Respiratory illness associated with EV-D68 infection ranges from mild illness
that just needs outpatient service to severe illness requiring intensive care and
mechanical ventilation. To date, there are no specific medicines and vaccines to
treat or prevent EV-D68 infection. This review provides a detailed overview about
our current understanding of EV-D68-related virology, epidemiology and clinical
syndromes, pathogenesis, and laboratory diagnostics.
PMID- 27486739
TI - Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in
Treatment and Prevention.
AB - Adenoviruses (AdVs) are DNA viruses that typically cause mild infections
involving the upper or lower respiratory tract, gastrointestinal tract, or
conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis,
hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis.
AdV infections are more common in young children, due to lack of humoral
immunity. Epidemics of AdV infection may occur in healthy children or adults in
closed or crowded settings (particularly military recruits). The disease is more
severe and dissemination is more likely in patients with impaired immunity (e.g.,
organ transplant recipients, human immunodeficiency virus infection). Fatality
rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%.
More than 50 serotypes of AdV have been identified. Different serotypes display
different tissue tropisms that correlate with clinical manifestations of
infection. The predominant serotypes circulating at a given time differ among
countries or regions, and change over time. Transmission of novel strains between
countries or across continents and replacement of dominant viruses by new strains
may occur. Treatment of AdV infections is controversial, as prospective,
randomized therapeutic trials have not been conducted. Cidofovir is the drug of
choice for severe AdV infections, but not all patients require treatment. Live
oral vaccines are highly efficacious in reducing the risk of respiratory AdV
infection and are in routine use in the military in the United States, but
currently are not available to civilians.
PMID- 27486740
TI - Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology,
Management, and Outcomes.
AB - Among immunocompromised individuals, members of the human Herpesviridae family
are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and
2, varicella zoster virus, Epstein-Barr virus, and human herpesvirus-6, -7, and
8 all establish latency after infection and can reactivate during periods of
immunosuppression, leading to both direct and indirect adverse effects on the
host including severe organ dysfunction as well as allograft rejection and loss
after transplantation. While not all herpesviruses are primary respiratory
pathogens, many of their manifestations include involvement of the respiratory
tract. This article discusses the individual viruses, their epidemiology, and
clinical manifestations as well as recommended treatment and preventive
strategies.
PMID- 27486741
TI - Control Measures for Human Respiratory Viral Infection.
AB - New viral respiratory pathogens are emerging with increasing frequency and have
potentially devastating impacts on the population worldwide. Recent examples of
newly emerged threats include severe acute respiratory syndrome coronavirus, the
2009 H1N1 influenza pandemic, and Middle East respiratory syndrome coronavirus.
Experiences with these pathogens have shown up major deficiencies in how we deal
globally with emerging pathogens and taught us salient lessons in what needs to
be addressed for future pandemics. This article reviews the lessons learnt from
past experience and current knowledge on the range of measures required to limit
the impact of emerging respiratory infections from public health responses down
to individual patient management. Key areas of interest are surveillance
programs, political limitations on our ability to respond quickly enough to
emerging threats, media management, public information dissemination, infection
control, prophylaxis, and individual patient management. Respiratory physicians
have a crucial role to play in many of these areas and need to be aware of how to
respond as new viral pathogens emerge.
PMID- 27486742
TI - Antivirals for Respiratory Viral Infections: Problems and Prospects.
AB - In the past two decades, several newly emerging and reemerging viral respiratory
pathogens including several influenza viruses (avian influenza and pandemic
influenza), severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle
East respiratory syndrome coronavirus (MERS-CoV), have continued to challenge
medical and public health systems. Thereafter, the development of cost-effective,
broad-spectrum antiviral agents is the urgent mission of both virologists and
pharmacologists. Current antiviral developments have focused targets on viral
entry, replication, release, and intercellular pathways essential for viral life
cycle. Here, we review the current literature on challenges and prospects in the
development of these antivirals.
PMID- 27486743
TI - Distinct Skeletal Muscle Gene Regulation from Active Contraction, Passive
Vibration, and Whole Body Heat Stress in Humans.
AB - Skeletal muscle exercise regulates several important metabolic genes in humans.
We know little about the effects of environmental stress (heat) and mechanical
stress (vibration) on skeletal muscle. Passive mechanical stress or systemic heat
stress are often used in combination with many active exercise programs. We
designed a method to deliver a vibration stress and systemic heat stress to
compare the effects with active skeletal muscle contraction. PURPOSE: The purpose
of this study is to examine whether active mechanical stress (muscle
contraction), passive mechanical stress (vibration), or systemic whole body heat
stress regulates key gene signatures associated with muscle metabolism,
hypertrophy/atrophy, and inflammation/repair. METHODS: Eleven subjects, six able
bodied and five with chronic spinal cord injury (SCI) participated in the study.
The six able-bodied subjects sat in a heat stress chamber for 30 minutes. Five
subjects with SCI received a single dose of limb-segment vibration or a dose of
repetitive electrically induced muscle contractions. Three hours after the
completion of each stress, we performed a muscle biopsy (vastus lateralis or
soleus) to analyze mRNA gene expression. RESULTS: We discovered repetitive active
muscle contractions up regulated metabolic transcription factors NR4A3 (12.45
fold), PGC-1alpha (5.46 fold), and ABRA (5.98 fold); and repressed MSTN (0.56
fold). Heat stress repressed PGC-1alpha (0.74 fold change; p < 0.05); while
vibration induced FOXK2 (2.36 fold change; p < 0.05). Vibration similarly caused
a down regulation of MSTN (0.74 fold change; p < 0.05), but to a lesser extent
than active muscle contraction. Vibration induced FOXK2 (p < 0.05) while heat
stress repressed PGC-1alpha (0.74 fold) and ANKRD1 genes (0.51 fold; p < 0.05).
CONCLUSION: These findings support a distinct gene regulation in response to heat
stress, vibration, and muscle contractions. Understanding these responses may
assist in developing regenerative rehabilitation interventions to improve muscle
cell development, growth, and repair.
PMID- 27486744
TI - Rabies in Kazakhstan.
AB - BACKGROUND: Rabies is a neglected zoonotic disease. There is a sparsity of data
on this disease with regard to the incidence of human and animal disease in many
low and middle income countries. Furthermore, rabies results in a large economic
impact and a high human burden of disease. Kazakhstan is a large landlocked
middle income country that gained independence from the Soviet Union in 1991 and
is endemic for rabies. METHODOLOGY/PRINCIPAL FINDINGS: We used detailed public
health and veterinary surveillance data from 2003 to 2015 to map where livestock
rabies is occurring. We also estimate the economic impact and human burden of
rabies. Livestock and canine rabies occurred over most of Kazakhstan, but there
were regional variations in disease distribution. There were a mean of 7.1
officially recorded human fatalities due to rabies per year resulting in
approximately 457 Disability Adjusted Life Years (DALYs). A mean of 64,289
individuals per annum underwent post exposure prophylaxis (PEP) which may have
resulted in an additional 1140 DALYs annually. PEP is preventing at least 118
cases of human rabies each year or possibly as many as 1184 at an estimated cost
of $1193 or $119 per DALY averted respectively. The estimated economic impact of
rabies in Kazakhstan is $20.9 million per annum, with nearly half of this cost
being attributed to the cost of PEP and the loss of income whilst being treated.
A further $5.4 million per annum was estimated to be the life time loss of income
for fatal cases. Animal vaccination programmes and animal control programmes also
contributed substantially to the economic losses. The direct costs due to rabies
fatalities of agricultural animals was relatively low. CONCLUSIONS/SIGNIFICANCE:
This study demonstrates that in Kazakhstan there is a substantial economic cost
and health impact of rabies. These costs could be reduced by modifying the
vaccination programme that is now practised. The study also fills some data gaps
on the epidemiology and economic effects of rabies in respect to Kazakhstan.
PMID- 27486745
TI - Referrals between Public Sector Health Institutions for Women with Obstetric High
Risk, Complications, or Emergencies in India - A Systematic Review.
AB - Emergency obstetric care (EmOC) within primary health care systems requires a
linked referral system to be effective in reducing maternal death. This
systematic review aimed to summarize evidence on the proportion of referrals
between institutions during pregnancy and delivery, and the factors affecting
referrals, in India. We searched 6 electronic databases, reviewed four regional
databases and repositories, and relevant program reports from India published
between 1994 and 2013. All types of study or reports (except editorials, comments
and letters) which reported on institution-referrals (out-referral or in
referral) for obstetric care were included. Results were synthesized on the
proportion and the reasons for referral, and factors affecting referrals. Of the
11,346 articles identified by the search, we included 232 articles in the full
text review and extracted data from 16 studies that met our inclusion criteria Of
the 16, one was RCT, seven intervention cohort (without controls), six cross
sectional, and three qualitative studies. Bias and quality of studies were
reported. Between 25% and 52% of all pregnancies were referred from Sub-centres
for antenatal high-risk, 14% to 36% from nurse run delivery or basic EmOC centres
for complications or emergencies, and 2 to 7% were referred from doctor run basic
EmOC centres for specialist care at comprehensive EmOC centres. Problems
identified with referrals from peripheral health centres included low skills and
confidence of staff, reluctance to induce labour, confusion over the clinical
criteria for referral, non-uniform standards of care at referral institutions, a
tendency to by-pass middle level institutions, a lack of referral communication
and supervision, and poor compliance. The high proportion of referrals from
peripheral health centers reflects the lack of appropriate clinical guidelines,
processes, and skills for obstetric care and referral in India. This, combined
with inadequate referral communication and low compliance, is likely to
contribute to gaps and delays in the provision of emergency obstetric care.
PMID- 27486746
TI - Host Biomarkers for Distinguishing Bacterial from Non-Bacterial Causes of Acute
Febrile Illness: A Comprehensive Review.
AB - BACKGROUND: In resource limited settings acute febrile illnesses are often
treated empirically due to a lack of reliable, rapid point-of-care diagnostics.
This contributes to the indiscriminate use of antimicrobial drugs and poor
treatment outcomes. The aim of this comprehensive review was to summarize the
diagnostic performance of host biomarkers capable of differentiating bacterial
from non-bacterial infections to guide the use of antibiotics. METHODS: Online
databases of published literature were searched from January 2010 through April
2015. English language studies that evaluated the performance of one or more host
biomarker in differentiating bacterial from non-bacterial infection in patients
were included. Key information extracted included author information, study
methods, population, pathogens, clinical information, and biomarker performance
data. Study quality was assessed using a combination of validated criteria from
the QUADAS and Lijmer checklists. Biomarkers were categorized as hematologic
factors, inflammatory molecules, cytokines, cell surface or metabolic markers,
other host biomarkers, host transcripts, clinical biometrics, and combinations of
markers. FINDINGS: Of the 193 citations identified, 59 studies that evaluated
over 112 host biomarkers were selected. Most studies involved patient populations
from high-income countries, while 19% involved populations from low- and middle
income countries. The most frequently evaluated host biomarkers were C-reactive
protein (61%), white blood cell count (44%) and procalcitonin (34%). Study
quality scores ranged from 23.1% to 92.3%. There were 9 high performance host
biomarkers or combinations, with sensitivity and specificity of >=85% or either
sensitivity or specificity was reported to be 100%. Five host biomarkers were
considered weak markers as they lacked statistically significant performance in
discriminating between bacterial and non-bacterial infections. DISCUSSION: This
manuscript provides a summary of host biomarkers to differentiate bacterial from
non-bacterial infections in patients with acute febrile illness. Findings provide
a basis for prioritizing efforts for further research, assay development and
eventual commercialization of rapid point-of-care tests to guide use of
antimicrobials. This review also highlights gaps in current knowledge that should
be addressed to further improve management of febrile patients.
PMID- 27486747
TI - Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney
Disease.
AB - Skeletal muscle atrophy and impaired muscle function are associated with lower
health-related quality of life, and greater disability and mortality risk in
those with chronic kidney disease (CKD). However, the pathogenesis of skeletal
dysfunction in CKD is unknown. We used a slow progressing, naturally occurring,
CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical
presentations of CKD to study skeletal muscle signaling. The CKD rats
demonstrated augmented skeletal muscle regeneration with higher activation and
differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and
myogenin RNA expression). However, there was also higher expression of
proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD
animals had higher indices of oxidative stress compared to normal, evident by
elevated plasma levels of an oxidative stress marker, 8-hydroxy-2'
deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase
(SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show
significantly higher serum levels of myostatin and expression of myostatin in
skeletal muscle of CKD animals compared to normal. Taken together, these data
show aberrant regeneration and proteolytic signaling that is associated with
oxidative stress and high levels of myostatin in the setting of CKD. These
changes likely play a role in the compromised skeletal muscle function that
exists in CKD.
PMID- 27486748
TI - Hypnotizability and Placebo Analgesia in Waking and Hypnosis as Modulators of
Auditory Startle Responses in Healthy Women: An ERP Study.
AB - We evaluated the influence of hypnotizability, pain expectation, placebo
analgesia in waking and hypnosis on tonic pain relief. We also investigated how
placebo analgesia affects somatic responses (eye blink) and N100 and P200 waves
of event-related potentials (ERPs) elicited by auditory startle probes. Although
expectation plays an important role in placebo and hypnotic analgesia, the neural
mechanisms underlying these treatments are still poorly understood. We used the
cold cup test (CCT) to induce tonic pain in 53 healthy women. Placebo analgesia
was initially produced by manipulation, in which the intensity of pain induced by
the CCT was surreptitiously reduced after the administration of a sham analgesic
cream. Participants were then tested in waking and hypnosis under three
treatments: (1) resting (Baseline); (2) CCT-alone (Pain); and (3) CCT plus
placebo cream for pain relief (Placebo). For each painful treatment, we assessed
pain and distress ratings, eye blink responses, N100 and P200 amplitudes. We used
LORETA analysis of N100 and P200 waves, as elicited by auditory startle, to
identify cortical regions sensitive to pain reduction through placebo and
hypnotic analgesia. Higher pain expectation was associated with higher pain
reductions. In highly hypnotizable participants placebo treatment produced
significant reductions of pain and distress perception in both waking and
hypnosis condition. P200 wave, during placebo analgesia, was larger in the
frontal left hemisphere while placebo analgesia, during hypnosis, involved the
activity of the left hemisphere including the occipital region. These findings
demonstrate that hypnosis and placebo analgesia are different processes of top
down regulation. Pain reduction was associated with larger EMG startle
amplitudes, N100 and P200 responses, and enhanced activity within the frontal,
parietal, and anterior and posterior cingulate gyres. LORETA results showed that
placebo analgesia modulated pain-responsive areas known to reflect the ongoing
pain experience.
PMID- 27486750
TI - Risk Factors and Relationship of Cutaneous and Uveal Melanocytic Lesions in
Monozygotic and Dizygotic Twin Pairs.
AB - BACKGROUND: The similar genetic background of a pair of twins, and the similar
environmental impacts to which they are exposed allow an exact and objective
investigation of various constitutional and environmental factors in naevus
development. As far as we are aware, this is the first published survey that
simultaneously examines cutaneous and ocular pigmented lesions in an appreciable
sample of identical and non-identical twins. METHODS: 172 pairs of twins of
Caucasian origin were included in this study. A whole-body skin examination and a
detailed ophthalmological examination were performed to determine the density of
melanocytic lesions. A standardized questionnaire was used to assess the data
relating to constitutional, sun exposure and other variables. RESULTS: A notably
high proportion of the subjects (36.78%) manifested one or more clinically
atypical melanocytic naevi (CAMNs), and approximately one-third (31.4%) of them
at least one benign uveal pigmented lesion (BUPL). The incidence of iris freckles
(IFs), iris naevi (INs) and choroidal naevi (CHNs) proved to be 25.35%, 5.98% and
3.52%, respectively. The interclass correlation coefficients for common
melanocytic naevi (CMNs), CAMNs, and INs were 0.77, 0.76 and 0.86 in monozygotic
twins, as compared with 0.5, 0.27 and 0.25 in dizygotic twin pairs, respectively.
A statistically significant correlation was found between the prevalence of CAMNs
and that of INs. CONCLUSIONS: This significant correlation suggests the existence
of a subgroup of Caucasian people with an increased susceptibility to both
cutaneous and ocular naevus formation. There is accumulating evidence that,
besides the presence of cutaneous atypical naevi, INs can serve as a marker of a
predisposed phenotype at risk of uveal melanoma. The correlation between
cutaneous and ocular pigmented lesions underlines the need for the adequate
ophthalmological screening of subjects with CAMNs and INs.
PMID- 27486749
TI - In Vitro Inhibition of NFAT5-Mediated Induction of CCL2 in Hyperosmotic
Conditions by Cyclosporine and Dexamethasone on Human HeLa-Modified Conjunctiva
Derived Cells.
AB - PURPOSE: To investigate the pro-inflammatory intracellular mechanisms induced by
an in vitro model of dry eye disease (DED) on a Hela-modified conjunctiva-derived
cells in hyperosmolarity (HO) stress conditions. This study focused on CCL2
induction and explored the implications of the nuclear factor of activated T
cells 5 (NFAT5) as well as mitogen-activated protein kinases (MAPK) and nuclear
factor kappa B (NFKB). This work was completed by an analysis of the effects of
cyclosporine A (CsA), dexamethasone (Dex) and doxycycline (Dox) on HO-induced
CCL2 and NFAT5 induction. METHODS: A human HeLa-modified conjunctiva-derived cell
line was cultured in NaCl-hyperosmolar medium for various exposure times.
Cellular viability, CCL2 secretion, NFAT5 and CCL2 gene expression, and
intracytoplasmic NFAT5 were assessed using the Cell Titer Blue(r) assay, enzyme
linked immunosorbent assay (ELISA), RT-qPCR and immunostaining, respectively. In
selected experiments, inhibitors of MAPKs or NFkappaB, therapeutic agents or
NFAT5 siRNAs were added before the hyperosmolar stimulations. RESULTS: HO induced
CCL2 secretion and expression as well as NFAT5 gene expression and translocation.
Adding NFAT5-siRNA before hyperosmolar stimulation led to a complete inhibition
of CCL2 induction and to a decrease in cellular viability. p38 MAPK (p38), c-Jun
NH2-terminal kinase (JNK) and NFKB inhibitors, CsA and Dex induced a partial
inhibition of HO-induced CCL2, while Dox and extracellular signal-regulated
kinase (ERK) inhibitor did not. Dex also induced a partial inhibition of HO
induced NFAT5 gene expression but not CsA or Dox. CONCLUSIONS: These in vitro
results suggest a potential role of CCL2 in DED and highlight the crucial role of
NFAT5 in the pro-inflammatory effect of HO on HeLa-modified conjunctiva-derived
cells, a rarely studied cellular type. This inflammatory pathway involving NFAT5
and CCL2 could offer a promising target for developing new therapies to treat
DED, warranting further investigations to fully grasp the complete intracellular
mechanisms.
PMID- 27486751
TI - Exopolysaccharide Production by Sinorhizobium fredii HH103 Is Repressed by
Genistein in a NodD1-Dependent Manner.
AB - In the rhizobia-legume symbiotic interaction, bacterial surface polysaccharides,
such as exopolysaccharide (EPS), lipopolysaccharide (LPS), K-antigen
polysaccharide (KPS) or cyclic glucans (CG), appear to play crucial roles either
acting as signals required for the progression of the interaction and/or
preventing host defence mechanisms. The symbiotic significance of each of these
polysaccharides varies depending on the specific rhizobia-legume couple. In this
work we show that the production of exopolysaccharide by Sinorhizobium fredii
HH103, but not by other S. fredii strains such as USDA257 or NGR234, is repressed
by nod gene inducing flavonoids such as genistein and that this repression is
dependent on the presence of a functional NodD1 protein. In agreement with the
importance of EPS for bacterial biofilms, this reduced EPS production upon
treatment with flavonoids correlates with decreased biofilm formation ability. By
using quantitative RT-PCR analysis we show that expression of the exoY2 and exoK
genes is repressed in late stationary cultures of S. fredii HH103 upon treatment
with genistein. Results presented in this work show that in S. fredii HH103 EPS
production is regulated just in the opposite way than other bacterial signals
such as Nod factors and type 3 secreted effectors: it is repressed by flavonoids
and NodD1 and enhanced by the nod repressor NolR. These results are in agreement
with our previous observations showing that lack of EPS production by S. fredii
HH103 is not only non-detrimental but even beneficial for symbiosis with soybean.
PMID- 27486752
TI - Personality and Body-Mass-Index in School-Age Children: An Exploration of
Mediating and Moderating Variables.
AB - This study explored longitudinal associations between personality and body-mass
index (BMI) in school-age children, including the potential mediating role of
screen time and physical activity, and the potential moderating roles of child
demographics and neighbourhood socioeconomic position. Participants were the
parents (and teachers) of 3857 ten-year-old children, who completed
questionnaires at baseline with a two-year follow-up. After controlling for child
demographics (e.g., sex, pubertal status), we found that personality was
unimportant for concurrent BMI, but was important for subsequent BMI and change
in BMI over two years. Low levels of introversion and persistence at baseline,
and decreases in persistence over time, were associated with a higher BMI at
follow-up and a greater increase in BMI over time. Moderator analyses showed that
introversion was more strongly related to subsequent BMI for children listed as
aboriginal or Torres Strait Islander. The relationship between personality and
change in BMI was mediated by screen time, but not by physical activity. To
conclude, findings demonstrate that personality is important for change in body
mass in Australian children (particularly indigenous children), and that screen
based sedentary behaviour features an important role in this association.
PMID- 27486753
TI - Mechanism of BRG1 silencing in primary cancers.
AB - BRG1 (SMARCA4) is a documented tumor suppressor and a key subunit of the SWI/SNF
chromatin remodeling complex that is silenced in many cancer types. Studies have
shown that BRG1 is mutated in cancer-derived cell lines, which led to the
assertion that BRG1 is also mutated in primary human tumors. However, the
sequencing of BRG1-deficient tumors has revealed a paucity of mutations; hence,
the cause of BRG1 silencing in tumors remains an enigma. We conducted
immunohistochemistry (IHC) on a number of tumor microarrays to characterize the
frequency of BRG1 loss in different tumor types. We also analyzed BRG1-deficient
tumors by sequencing the genomic DNA and the mRNA. We then tested if BRG1
expression could be induced in BRG1-negative cell lines (i.e., that lack
mutations in BRG1) after the application of several different epigenetic agents,
including drugs that inhibit the AKT pathway. We found that a subset of BRG1
negative cell lines also demonstrated aberrant splicing of BRG1, and in at least
30% of BRG1-deficient tumors, BRG1 expression appeared to be suppressed due to
aberrant BRG1 splicing. As the majority of BRG1-deficient tumors lack mutations
or splicing defects that could drive BRG1 loss of expression, this suggests that
other mechanisms underlie BRG1 silencing. To this end, we analyzed 3 BRG1
deficient nonmutated cancer cell lines and found that BRG1 was inducible in these
cell lines upon inhibition of the AKT pathway. We show that the loss of BRG1 is
associated with the loss of E-cadherin and up-regulation of Vimentin in primary
tumors, which explains why BRG1 loss is associated with a poor prognosis in
multiple tumor types.
PMID- 27486754
TI - Inhibition of cyclin dependent kinase 9 by dinaciclib suppresses cyclin B1
expression and tumor growth in triple negative breast cancer.
AB - Cyclin-dependent kinases (CDKs) are potential cancer therapeutic targets because
of their critical role in promoting cell growth. Dinaciclib is a novel CDK
inhibitor currently under clinical evaluation for the treatment of advanced
malignancies. In this study, we demonstrated the anti-tumor activity of
dinaciclib in triple negative breast cancer (TNBC) patient derived xenograft
(PDX) and cell lines in vitro and in vivo. Treatment with dinaciclib induced cell
cycle arrest at G2/M phase and marked apoptosis. These changes were accompanied
by reduced phosphorylation of CDK1 and retinoblastoma (Rb) protein and decreased
protein levels of cyclin B1, cMYC and survivin. We further demonstrated that
siRNA knockdown of CDK9, the kinase subunit of positive transcription elongation
factor b (P-TEFb), instead of CDK1 or CDK2, reduced the levels of cyclin B1 and
MYC in TNBC cell lines. These data support the importance of CDK9, in addition to
CDK1, in mediating the growth inhibitory effect of dinaciclib in TNBC. Further
investigation of CDK9 as a therapeutic target in TNBC is needed.
PMID- 27486755
TI - Fulvestrant inhibits growth of triple negative breast cancer and synergizes with
tamoxifen in ERalpha positive breast cancer by up-regulation of ERbeta.
AB - The estrogen receptor-alpha (ERalpha) is used as a predictive marker for anti
estrogen therapy in breast cancer patients. In addition to aromatase inhibitors,
ERalpha can be targeted at the receptor level using the receptor modulator
tamoxifen or by the pure anti-estrogen fulvestrant. The role of the second ER, ER
beta (ERbeta), as a therapeutic target or prognostic marker in breast cancer is
still elusive. Hitherto, it is not known if ERalpha+/ERbeta+ breast cancers would
benefit from a treatment strategy combining tamoxifen and fulvestrant or if
fulvestrant exert any therapeutic effects in ERalpha-/ERbeta+ breast cancer.
Here, we report that fulvestrant up-regulated ERbeta in ERalpha+/ERbeta+ breast
cancer and in triple negative ERbeta+ breast cancers (ERalpha-/ERbeta+). In
ERalpha+/ERbeta+ breast cancer, a combination therapy of tamoxifen and
fulvestrant significantly reduced tumor growth compared to either treatment alone
both in vivo and in vitro. In ERalpha-/ERbeta+ breast cancer fulvestrant had
potent effects on cancer growth, in vivo as well as in vitro, and this effect was
dependent on intrinsically expressed levels of ERbeta. The role of ERbeta was
further confirmed in cells where ERbeta was knocked-in or knocked-down.
Inhibition of DNA methyltransferase (DNMT) increased the levels of ERbeta and
fulvestrant exerted similar potency on DNMT activity as the DNMT inhibitor
decitabine. We conclude that fulvestrant may have therapeutic potential in
additional groups of breast cancer patients; i) in ERalpha+/ERbeta+ breast cancer
where fulvestrant synergizes with tamoxifen and ii) in triple negative/ERbeta+
breast cancer patients, a subgroup of breast cancer patients with poor prognosis.
PMID- 27486756
TI - Simultaneous activation and inhibition of autophagy sensitizes cancer cells to
chemotherapy.
AB - While combined chemotherapy (CT) with an autophagy inducer and an autophagy
inhibitor appears paradoxical, it may provide a more effective perturbation of
autophagy pathways. We used two dissimilar cell lines to test the hypothesis that
autophagy is the common denominator of cell fate after CT. HA22T cells are
characterized by CT-induced apoptosis and use autophagy to prevent cell death,
while Huh7.5.1 cells exhibit sustained autophagic morphology after CT. Combined
CT and rapamycin treatment resulted in a better combination index (CI) in
Huh7.5.1 cells than combined CT and chloroquine, while the reverse was true in
HA22T cells. The combination of 3 drugs (triplet drug treatment) had the best CI.
After triplet drug treatment, HA22T cells switched from protective autophagy to
mitochondrial membrane permeabilization and endoplasmic reticulum stress response
induced apoptosis, while Huh7.5.1 cells intensified autophagic lethality. Most
importantly, both cell lines showed activation of Akt after CT, while the triplet
combination blocked Akt activation through inhibition of phospholipid lipase D
activity. This novel finding warrants further investigation as a broad
chemosensitization strategy.
PMID- 27486758
TI - Circulating tumor cells: A promising marker of predicting tumor response in
rectal cancer patients receiving neoadjuvant chemo-radiation therapy.
AB - PURPOSE: The aim of this study was to investigate the role of circulating tumor
cells (CTCs) in assessing and predicting tumor response to neoadjuvant
chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC).
METHODS: A total of 115 patients with T3-4 and/or N+ rectal cancer were enrolled.
All patients received neoadjuvant CRT followed by radical surgery after 6-8
weeks. The pathological results after surgery were evaluated according to tumor
regression grade (TRG) classification. RESULTS: Based on TRG score, patients were
classified as responders (TRG3-4) and non-responders (TRG0-2). The baseline CTC
counts of responders were significantly higher than those of non-responders
(44.50+/-11.94 vs. 37.67+/-15.45, P=0.012). By contrast, the post-CRT CTC counts
of responders were significantly lower than those of non-responders (3.61+/-2.90
vs. 12.08+/-7.40, P<0.001). According to ROC analysis, Delta%CTC (percentage
difference in CTC counts between baseline and post-CRT) was identified as the
stronger predictor to discriminate responders from non-responders (AUC: 0.860).
The results of multivariate analysis also indicated that post-CRT CTC counts and
Delta%CTC were significantly and independently associated with tumor response to
CRT. CONCLUSIONS: The detection of CTCs is a powerful and promising tool for
evaluating and predicting responses to neoadjuvant CRT in LARC patients.
PMID- 27486757
TI - The breast cancer susceptibility-related polymorphisms at the TOX3/LOC643714
locus associated with lung cancer risk in a Han Chinese population.
AB - It has been well established that besides environmental factors, genetic factors
are also associated with lung cancer risk. However, to date, the prior identified
genetic variants and loci only explain a small fraction of the familial risk of
lung cancer. Hence it is vital to investigate the remaining missing heritability
to understand the development and process of lung cancer. In the study, to test
our hypothesis that the previously identified breast cancer risk-associated
genetic polymorphisms at the TOX3/LOC643714 locus might contribute to lung cancer
risk, 16 SNPs at the TOX3/LOC643714 locus were evaluated in a Han Chinese
population based on a case-control study. Pearson's chi-square test or Fisher's
exact test revealed that rs9933638, rs12443621, and rs3104746 were significantly
associated with lung cancer risk (P < 0.001, P < 0.001, and P = 0.005,
respectively). Logistic regression analyses displayed that lung cancer risk of
individuals with rs9933638(GG+GA) were 1.89 times higher than that of rs9933638AA
carriers (OR = 1.893, 95% CI = 1.308-2.741, P = 0.001). Similar findings were
manifested for rs12443621 (OR = 1.824, 95% CI = 1.272-2.616, P = 0.001,
rs12443621(GG+GA) carriers vs. rs12443621AA carriers) and rs3104746 (OR = 1.665,
95% CI = 1.243-2.230, P = 0.001, rs3104746TT carriers vs. rs3104746(TA+AA)
carriers). The study discovered for the first time that three SNPs (rs9933638,
rs12443621, and rs3104746) at the TOX3/LOC643714 locus contributed to lung cancer
risk, providing new evidences that lung cancer and breast cancer are linked at
the molecular and genetic level to a certain extent.
PMID- 27486759
TI - Chemo-immunotherapy induces tumor regression in a mouse model of spontaneous
mammary carcinogenesis.
AB - Tumor-specific immune tolerance represents an obstacle for the development of
effective anti-tumor immune responses through cancer vaccines. We here evaluated
the efficacy of chemo-immunotherapy in breaking tumor-specific immune tolerance
in an almost incurable mouse model of spontaneous carcinogenesis.Transgenic HER
2/neu mice bearing large mammary tumors received the adoptive transfer of
splenocytes and serum isolated from immune donors, with or without pre
conditioning with cyclophosphamide. Treatment efficacy was assessed by monitoring
tumor growth by manual inspection and by magnetic resonance imaging. The same
chemo-immunotherapy protocol was tested on tumor-free HER-2/neu mice, to evaluate
the effects on tumor emergence.Our data show that chemo-immunotherapy hampered
carcinogenesis and caused the regression of large mammary tumor lesions in tumor
bearing HER-2/neu mice. The complete eradication of a significant number of tumor
lesions occurred only in mice receiving cyclophosphamide shortly before
immunotherapy, and was associated with increased serum anti HER-2/p185 antibodies
and tumor leukocyte infiltration. The same protocol significantly delayed the
appearance of mammary tumors when administered to tumor-free HER-2/neu mice,
indicating that this chemo-immunotherapy approach acted through the elicitation
of an effective anti-tumor immune response. Overall, our data support the immune
modulatory role of chemotherapy in overcoming cancer immune tolerance when
administered at lymphodepleting non-myeloablative doses shortly before transfer
of antigen-specific immune cells and immunoglobulins. These findings open new
perspectives on combining immune-modulatory chemotherapy and immunotherapy to
overcome immune tolerance in cancer patients.
PMID- 27486760
TI - Combining GRP78 suppression and MK2206-induced Akt inhibition decreases
doxorubicin-induced P-glycoprotein expression and mitigates chemoresistance in
human osteosarcoma.
AB - P-glycoprotein (P-gp) overexpression is associated with poor prognosis and drug
resistance in osteosarcoma (OS), but the underlying mechanisms remain
incompletely understood. Here, we examined the regulation of P-gp, GRP78, and
phospho-Akt in doxorubicin (DOX)-treated OS cells. DOX induced P-gp expression,
which was associated with increased GRP78 levels and Akt activation in vitro and
in vivo. Functional analysis showed that Akt induces P-gp and GRP78 expression,
which contributes to the DOX-induced Akt activation. Examination of the
relationship between Akt and GRP78 demonstrated that GRP78 suppression attenuates
the Akt activity in OS parental sensitive and resistant cells, indicating that
GRP78 is required for full Akt activity. Inhibition of Akt activity using MK2206
decreased GRP78 expression in OS cells, which enhanced the inhibitory effect of
MK2206 on P-gp expression. GRP78 knockdown combined with MK2206 suppressed the
development of DOX resistance in OS cells and inhibited the in vivo tumor growth
in the presence of DOX. These results support the development of novel
therapeutic strategies that target GRP78 and Akt to sensitize OS cells for
chemotherapy.
PMID- 27486761
TI - Intratumoral heterogeneity of the therapeutical response to gemcitabine and
metformin.
AB - Cancer heterogeneity and microenvironmental aspects within a tumor are considered
key factors influencing resistance of carcinoma cells to distinct
chemotherapeutical agents. We evaluated a high concentration of metformin in
combination with gemcitabine on a syngeneic orthotopic mouse model using 6606PDA
cells. We observed reduced tumor size and reduced cancer cell proliferation after
three weeks of chemotherapy with either compound and noticed an additive effect
between gemcitabine and metformin on tumor weight. Interestingly, distinct areas
of the carcinoma responded differently to either compound. Metformin inhibited
the proliferation of cancer cells close to the desmoplastic reaction, whereas
gemcitabine inhibited the proliferation of cancer cells mainly 360-570 MUm
distant to the desmoplastic reaction. Indeed, co-culture of pancreatic stellate
cells with 6606PDA, 7265PDA or MIA PaCa-2 cells increased gemcitabine resistance.
Metformin resistance, however, was increased by high glucose concentration in the
medium. Other factors such as hypoxia or the pH of the medium had no influence on
gemcitabine or metformin induced inhibition of cancer cell proliferation. These
data demonstrate a spatial heterogeneity in drug resistance within pancreatic
adenocarcinomas and that microenvironmental aspects such as supply of glucose and
the presence of pancreatic stellate cells regulate cancer cell sensitivity
towards metformin or gemcitabine.
PMID- 27486763
TI - Inhibition of the colony-stimulating-factor-1 receptor affects the resistance of
lung cancer cells to cisplatin.
AB - In the present work we show that multiple lung cancer cell lines contain
cisplatin resistant cell subpopulations expressing the Colony-Stimulating-Factor
Receptor-1 (CSF-1R) and surviving chemotherapy-induced stress. By exploiting
siRNA-mediated knock down in vitro and the use of an investigational CSF-1R TKI
(JNJ-40346527) in vitro and in vivo, we show that expression and function of the
receptor are required for the clonogenicity and chemoresistance of the cell
lines. Thus, inhibition of the kinase activity of the receptor reduced the levels
of EMT-associated genes, stem cell markers and chemoresistance genes.
Additionally, the number of high aldehyde dehydrogenase (ALDH) expressing cells
was reduced, consequent to the lack of cisplatin-induced increase of ALDH
isoforms. This affected the collective chemoresistance of the treated cultures.
Treatment of tumor bearing mice with JNJ-40346527, at pharmacologically relevant
doses, produced strong chemo-sensitizing effects in vivo. These anticancer
effects correlated with a reduced number of CSF-1Rpos cells, in tumors excised
from the treated mice. Depletion of the CD45pos cells within the treated tumors
did not, apparently, play a major role in mediating the therapeutic response to
the TKI. Thus, lung cancer cells express a functional CSF-1 and CSF-1R duo which
mediates pro-tumorigenic effects in vivo and in vitro and can be targeted in a
therapeutically relevant way. These observations complement the already known
role for the CSF-1R at mediating the pro-tumorigenic properties of tumor
infiltrating immune components.
PMID- 27486764
TI - C-Myc functions as a competing endogenous RNA in acute promyelocytic leukemia.
AB - Recent reports have described a new post-transcriptional regulation that RNA
transcripts can crosstalk with each other by competing for their common
microRNAs. These RNA transcripts termed competing endogenous RNAs (ceRNAs)
regulate the distribution of miRNAs on their targets. One corollary from ceRNA
interaction is that chromosomal translocation in acute promyelocytic leukemia
(APL) would perturb ceRNA regulation due to altered expression of 3'UTRs. In our
study, we demonstrate that expression of PML/RARalpha, the APL-associated fusion
oncogene is repressed by c-Myc mRNA transcript independent of protein-coding
function but dependent upon microRNA. Attenuation of c-Myc transcript results in
PML/RARalpha-degraded cellular phenotypes in APL cells, but these Myc reduction
associated cell phenotypes are sufficient to abrogate in a microRNA dependent
manner. We also show that let-7 microRNA family members promote differentiation
of All-Trans-Retinoic Acid (ATRA)-induced NB4 cells and their activities are
affected by expression levels of both c-Myc and PML/RARalpha through altering
miRNA targets. These results indicate that c-Myc mRNA represses PML/RARalpha
expression via altering the distribution of let-7 miRNAs on their targets. Our
findings reveal a previously unrecognized role of c-Myc as a potential ceRNA for
PML/RARalpha in APL.
PMID- 27486766
TI - Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol
in gynecologic cancer cells.
AB - Inactivating mutations in ARID1A are found in a broad spectrum of cancer types,
with the highest frequency in gynecologic cancers. However, therapeutic
strategies targeting ARID1A-mutant cancer cells remain limited. In this study, we
aimed to identify drugs sensitivities in ARID1A-mutant cancer cell lines. By
analyzing the Genomics of Drug Sensitivity in Cancer database, we found that
ARID1A-mutant cancer cell lines were more sensitive to treatment with the
reactive oxygen species (ROS)-inducing agent elesclomol. In a panel of 14
gynecologic cancer cell lines, treatment with elesclomol inhibited growth and
induced apoptosis more potently in ARID1A-mutant cells. Knockdown of ARID1A in
RMG1 and OVCA432 ovarian cancer cells resulted in increased sensitivity to
elesclomol, whereas restoration of ARID1A expression in TOV21G ovarian cancer
cells resulted in increased resistance to elesclomol. Furthermore, we found that
knockdown of ARID1A expression resulted in increased intracellular ROS levels. In
ovarian clear cell carcinoma patient samples, low expression of ARID1A correlated
with high expression of 8-hydroxyguanosine, a marker for oxidative stress. In
summary, we demonstrate for the first time that loss of ARID1A leads to
accumulation of ROS and suggest that elesclomol may be used to target ARID1A
mutant gynecologic cancer cells.
PMID- 27486767
TI - Identification of genetic variants predictive of early onset pancreatic cancer
through a population science analysis of functional genomic datasets.
AB - Biomarkers are critically needed for the early detection of pancreatic cancer
(PC) are urgently needed. Our purpose was to identify a panel of genetic variants
that, combined, can predict increased risk for early-onset PC and thereby
identify individuals who should begin screening at an early age. Previously, we
identified genes using a functional genomic approach that were aberrantly
expressed in early pathways to PC tumorigenesis. We now report the discovery of
single nucleotide polymorphisms (SNPs) in these genes associated with early age
at diagnosis of PC using a two-phase study design. In silico and bioinformatics
tools were used to examine functional relevance of the identified SNPs. Eight
SNPs were consistently associated with age at diagnosis in the discovery phase,
validation phase and pooled analysis. Further analysis of the joint effects of
these 8 SNPs showed that, compared to participants carrying none of these
unfavorable genotypes (median age at PC diagnosis 70 years), those carrying 1-2,
3-4, or 5 or more unfavorable genotypes had median ages at diagnosis of 64, 63,
and 62 years, respectively (P = 3.0E-04). A gene-dosage effect was observed, with
age at diagnosis inversely related to number of unfavorable genotypes (Ptrend =
1.0E-04). Using bioinformatics tools, we found that all of the 8 SNPs were
predicted to play functional roles in the disruption of transcription factor
and/or enhancer binding sites and most of them were expression quantitative trait
loci (eQTL) of the target genes. The panel of genetic markers identified may
serve as susceptibility markers for earlier PC diagnosis.
PMID- 27486768
TI - Functional intratumoral lymphatics in patient-derived xenograft models of
squamous cell carcinoma of the uterine cervix: implications for lymph node
metastasis.
AB - Studies of cell line-derived human tumor xenografts have suggested that the
lymphatics seen in immunohistochemical preparations from non-peripheral regions
of tumors are nonfunctional. In this investigation, lymphangiogenesis,
hemangiogenesis, and lymph node metastasis were studied in patient-derived
xenograft (PDX) models of carcinoma of the uterine cervix. Lymph vessel density
(LVD) and blood vessel density (BVD) were measured in immunohistochemical
preparations. The expression of angiogenesis-related genes was investigated by
quantitative PCR. Lymphatic functionality was assessed with the ferritin assay,
and tumor interstitial fluid pressure (IFP) was measured with a Millar catheter.
The PDX models mirrored the angiogenesis and aggressiveness of the donor
patients' tumors, and two highly aggressive models developed functional
lymphatics within the tumor mass. Tumors with functional intratumoral lymphatics
showed low IFP, high LVD, high BVD, high expression of a large number of
angiogenesis-related genes, and high incidence of lymph node metastases. LVD
correlated with BVD, and lymph node metastasis was associated with high LVD and
high BVD. Nine angiogenesis-related genes associated with the development of
functional intratumoral lymhatics were identified. High expression of these
genes, high LVD, and high BVD may be important biomarkers for poor outcome in
cervix carcinoma.
PMID- 27486769
TI - Radio-frequency plasma polymerized biodegradable carrier for in vivo release of
cis-platinum.
AB - A low pressure plasma process based on plasma deposition has been used to develop
a drug delivery strategy. In this study, a drug delivery system based on
different layers of plasma co-polymerized Poly epsilon-caprolactone-Polyethylene
glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis
platinum (118 MUgm/cm2) was used as an anti-cancer drug and incorporated for
local delivery of the chemotherapeutic agent. The co-polymer layers and their
interaction with cancer cells were analyzed by scanning electron microscopy. Our
study showed that the plasma-PCL-PEG coated cellophane membranes, in which the
drug, was included did not modify the flexibility and appearance of the
membranes. This system was actively investigated as an alternative method of
controlling localized delivery of drug in vivo. The loading of the anti-cancer
drug was investigated by UV-VIS spectroscopy and its release from plasma
deposited implants against BALB/c mice liver tissues were analyzed through
histological examination and apoptosis by TUNEL assay. The histological
examination of liver tissues revealed that when the plasma-modified membranes
encapsulated the cis-platinum, the Glisson's capsule and liver parenchyma were
damaged. In all cases, inflammatory tissues and fibrosis cells were observed in
contact zones between the implant and the liver parenchyma. In conclusion, low
pressure plasma deposited uniform nano-layers of the co-polymers can be used for
controlled release of the drug in vivo.
PMID- 27486770
TI - A retrospective analysis in patients with EGFR-mutant lung adenocarcinoma: is
EGFR mutation associated with a higher incidence of brain metastasis?
AB - Lung adenocarcinomas are more commonly associated with brain metastases (BM).
Epidermal growth factor receptor (EGFR) mutations have been demonstrated to be
both predictive and prognostic for patients with lung adenocarcinoma. We aimed to
explore the potential association between EGFR mutation and the risk of BM in
pulmonary adenocarcinoma patients. Data of 234 patients from 2007 to 2014 were
retrospectively reviewed. A total of 108 patients had EGFR mutations in the
entire cohort. Among them, 76 patients developed BM during their disease course.
The incidence of BM was statistically higher in patients with EGFR mutations both
at initial diagnosis (P=0.014) and at last follow-up (P<0.001). Multivariate
logistic regression analysis revealed that EGFR mutation significantly increased
the risk of BM at initial diagnosis (OR=2.515, P=0.022). In patients without BM
at initial diagnosis, the accumulative rate of subsequent BM was significantly
higher with EGFR mutations (P=0.001). Multivariate Cox regression analysis
identified EGFR mutation as the only independent risk factor for subsequent BM
(HR=3.036, P=0.001). Patients with EGFR mutations demonstrated longer overall
survival (OS) after BM diagnosis than patients with wild-type EGFR (P=0.028). Our
data suggest that EGFR mutation is an independent predictive and prognostic risk
factor for BM and a positive predictive factor for OS in patients with BM.
PMID- 27486771
TI - The underlying mechanism of proinflammatory NF-kappaB activation by the
mTORC2/Akt/IKKalpha pathway during skin aging.
AB - Mammalian target of rapamycin complex 2 (mTORC2), one of two different enzymatic
complexes of mTOR, regulates a diverse set of substrates including Akt. mTOR
pathway is one of well-known mediators of aging process, however, its role in
skin aging has not been determined. Skin aging can be induced by physical age and
ultraviolet (UV) irradiation which are intrinsic and extrinsic factors,
respectively. Here, we report increased mTORC2 pathway in intrinsic and photo
induced skin aging, which is implicated in the activation of nuclear factor
kappaB (NF-kappaB). UVB-irradiated or aged mice skin revealed that mTORC2
activity and its component, rictor were significantly upregulated which in turn
increased Akt activation and Akt-dependent IkappaB kinase alpha (IKKalpha)
phosphorylation at Thr23 in vivo. We also confirmed that UVB induced the
mTORC2/Akt/IKKalpha signaling pathway with HaCaT human normal keratinocytes. The
increased mTORC2 signaling pathway during skin aging were associated to NF-kappaB
activation. Suppression of mTORC2 activity by the treatment of a mTOR small
inhibitor or knockdown of RICTOR partially rescued UVB-induced NF-kappaB
activation through the downregulation of Akt/IKKalpha activity. Our data
demonstrated the upregulation of mTORC2 pathway in intrinsic and photo-induced
skin aging and its role in IKKalpha/NF-kappaB activation. These data not only
expanded the functions of mTOR to skin aging but also revealed the therapeutic
potential of inhibiting mTORC2 in ameliorating both intrinsic skin aging and
photoaging.
PMID- 27486773
TI - Integrated analysis miRNA and mRNA profiling in patients with severe
oligozoospermia reveals miR-34c-3p downregulates PLCXD3 expression.
AB - Our previous research suggested that an integrated analysis of microRNA (miRNA)
and messenger RNA (mRNA) expression is helpful to explore miRNA-mRNA interactions
and to uncover the molecular mechanisms of male infertility. In this study,
microarrays were used to compare the differences in the miRNA and mRNA expression
profiles in the testicular tissues of severe oligozoospermia (SO) patients with
obstructive azoospermia (OA) controls with normal spermatogenesis. Four miRNAs
(miR-1246, miR-375, miR-410, and miR-758) and six mRNAs (SLC1A3, PRKAR2B, HYDIN,
WDR65, PRDX1, and ADATMS5) were selected to validate the microarray data using
quantitative real-time PCR. Using statistical calculations and bioinformatics
predictions, we identified 33 differentially expressed miRNAs and 1,239
differentially expressed mRNAs, among which one potential miRNA-target gene pair,
miR-34c-3p and PLCXD3 (Phosphatidylinositol-Specific Phospholipase C, X Domain
Containing 3), was identified. Immunohistochemical analysis indicated that PLCXD3
was located within the germ cells of the mouse and human testis. Moreover, we
found that miR-34c-3p was able to decrease PLCXD3 expression in mouse (GC-1 and
TM4) and human (NCM460) cell lines, presumably indicating the possibility that
miR-34c-3p acts as an intracellular mediator in germinal lineage differentiation.
Notably, we reported the expression of the PLCXD3 protein in a man with normal
spermatogenesis and the lack of the PLCXD3 protein in a man with SO. Therefore,
the identified miRNA and mRNA may represent a potentially novel molecular
regulatory network and therapeutic targets for the study or treatment of SO,
which might provide a better understanding of the molecular basis of
spermatogenesis dysfunction.
PMID- 27486772
TI - Decellularized scaffolds in regenerative medicine.
AB - Allogeneic organ transplantation remains the ultimate solution for end-stage
organ failure. Yet, the clinical application is limited by the shortage of donor
organs and the need for lifelong immunosuppression, highlighting the importance
of developing effective therapeutic strategies. In the field of regenerative
medicine, various regenerative technologies have lately been developed using
various biomaterials to address these limitations. Decellularized scaffolds,
derived mainly from various non-autologous organs, have been proved a
regenerative capability in vivo and in vitro and become an emerging treatment
approach. However, this regenerative capability varies between scaffolds as a
result of the diversity of anatomical structure and cellular composition of
organs used for decellularization. Herein, recent advances in scaffolds based on
organ regeneration in vivo and in vitro are highlighted along with aspects where
further investigations and analyses are needed.
PMID- 27486777
TI - Constrained Score Statistics Identify Genetic Variants Interacting with Multiple
Risk Factors in Barrett's Esophagus.
AB - Few gene-environment interactions (G * E) have been discovered in cancer
epidemiology thus far, in part due to the large number of possible G * E to be
investigated and inherent low statistical power of traditional analytic methods
for discovering G * E. We consider simultaneously testing for interactions
between several related exposures and a genetic variant in a genome-wide study.
To improve power, constrained testing strategies are proposed for multivariate
gene-environment interactions at two levels: interactions that have the same
direction (one-sided or bidirectional hypotheses) or are proportional to
respective exposure main effects (a variant of Tukey's one-degree test). Score
statistics were developed to expedite the genome-wide computation. We conducted
extensive simulations to evaluate validity and power performance of the proposed
statistics, applied them to the genetic and environmental exposure data for
esophageal adenocarcinoma and Barrett's esophagus from the Barretts Esophagus and
Esophageal Adenocarcinoma Consortium (BEACON), and discovered three loci
simultaneously interacting with gastresophageal reflux, obesity, and tobacco
smoking with genome-wide significance. These findings deepen understanding of the
genetic and environmental architecture of Barrett's esophagus and esophageal
adenocarcinoma.
PMID- 27486776
TI - Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl
Syndrome.
AB - Bardet-Biedl syndrome (BBS) is a defining ciliopathy, notable for extensive
allelic and genetic heterogeneity, almost all of which has been identified
through sequencing. Recent data have suggested that copy-number variants (CNVs)
also contribute to BBS. We used a custom oligonucleotide array comparative
genomic hybridization (aCGH) covering 20 genes that encode intraflagellar
transport (IFT) components and 74 ciliopathy loci to screen 92 unrelated
individuals with BBS, irrespective of their known mutational burden. We
identified 17 individuals with exon-disruptive CNVs (18.5%), including 13
different deletions in eight BBS genes (BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, BBS7,
BBS9, and NPHP1) and a deletion and a duplication in other ciliopathy-associated
genes (ALMS1 and NPHP4, respectively). By contrast, we found a single
heterozygous exon-disruptive event in a BBS-associated gene (BBS9) in 229 control
subjects. Superimposing these data with resequencing revealed CNVs to (1) be
sufficient to cause disease, (2) Mendelize heterozygous deleterious alleles, and
(3) contribute oligogenic alleles by combining point mutations and exonic CNVs in
multiple genes. Finally, we report a deletion and a splice site mutation in
IFT74, inherited under a recessive paradigm, defining a candidate BBS locus. Our
data suggest that CNVs contribute pathogenic alleles to a substantial fraction of
BBS-affected individuals and highlight how either deletions or point mutations in
discrete splice isoforms can induce hypomorphic mutations in genes otherwise
intolerant to deleterious variation. Our data also suggest that CNV analyses and
resequencing studies unbiased for previous mutational burden is necessary to
delineate the complexity of disease architecture.
PMID- 27486774
TI - Ubc13: the Lys63 ubiquitin chain building machine.
AB - Ubc13 is an ubiquitin E2 conjugating enzyme that participates with many different
E3 ligases to form lysine 63-linked (Lys63) ubiquitin chains that are critical to
signaling in inflammatory and DNA damage response pathways. Recent studies have
suggested Ubc13 as a potential therapeutic target for intervention in various
human diseases including several different cancers, alleviation of anti-cancer
drug resistance, chronic inflammation, and viral infections. Understanding a
potential therapeutic target from different angles is important to assess its
usefulness and potential pitfalls. Here we present a global review of Ubc13 from
its structure, function, and cellular activities, to its natural and chemical
inhibition. The aim of this article is to review the literature that directly
implicates Ubc13 in a biological function, and to integrate structural and
mechanistic insights into the larger role of this critical E2 enzyme. We discuss
observations of multiple Ubc13 structures that suggest a novel mechanism for
activation of Ubc13 that involves conformational change of the active site loop.
PMID- 27486778
TI - Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid
Arthritis.
AB - Despite the progress in human leukocyte antigen (HLA) causal variant mapping,
independent localization of major histocompatibility complex (MHC) risk from
classical HLA genes is challenging. Here, we conducted a large-scale MHC fine
mapping analysis of rheumatoid arthritis (RA) in a Japanese population (6,244 RA
cases and 23,731 controls) population by using HLA imputation, followed by a
multi-ethnic validation study including east Asian and European populations (n =
7,097 and 23,149, respectively). Our study identified an independent risk of a
synonymous mutation at HLA-DOA, a non-classical HLA gene, on anti-citrullinated
protein autoantibody (ACPA)-positive RA risk (p = 1.4 * 10(-9)), which
demonstrated a cis-expression quantitative trait loci (cis-eQTL) effect on HLA
DOA expression. Trans-ethnic comparison revealed different linkage disequilibrium
(LD) patterns in HLA-DOA and HLA-DRB1, explaining the observed HLA-DOA variant
risk heterogeneity among ethnicities, which was most evident in the Japanese
population. Although previous HLA fine-mapping studies have identified amino acid
polymorphisms of the classical HLA genes as driving genetic susceptibility to
disease, our study additionally identifies the dosage contribution of a non
classical HLA gene to disease etiology. Our study contributes to the
understanding of HLA immunology in human diseases and suggests the value of
incorporating additional ancestry in MHC fine-mapping.
PMID- 27486779
TI - Defining KIR and HLA Class I Genotypes at Highest Resolution via High-Throughput
Sequencing.
AB - The physiological functions of natural killer (NK) cells in human immunity and
reproduction depend upon diverse interactions between killer cell immunoglobulin
like receptors (KIRs) and their HLA class I ligands: HLA-A, HLA-B, and HLA-C. The
genomic regions containing the KIR and HLA class I genes are unlinked,
structurally complex, and highly polymorphic. They are also strongly associated
with a wide spectrum of diseases, including infections, autoimmune disorders,
cancers, and pregnancy disorders, as well as the efficacy of transplantation and
other immunotherapies. To facilitate study of these extraordinary genes, we
developed a method that captures, sequences, and analyzes the 13 KIR genes and
HLA-A, HLA-B, and HLA-C from genomic DNA. We also devised a bioinformatics
pipeline that attributes sequencing reads to specific KIR genes, determines copy
number by read depth, and calls high-resolution genotypes for each KIR gene. We
validated this method by using DNA from well-characterized cell lines, comparing
it to established methods of HLA and KIR genotyping, and determining KIR
genotypes from 1000 Genomes sequence data. This identified 116 previously
uncharacterized KIR alleles, which were all demonstrated to be authentic by
sequencing from source DNA via standard methods. Analysis of just two KIR genes
showed that 22% of the 1000 Genomes individuals have a previously uncharacterized
allele or a structural variant. The method we describe is suited to the large
scale analyses that are needed for characterizing human populations and defining
the precise HLA and KIR factors associated with disease. The methods are
applicable to other highly polymorphic genes.
PMID- 27486780
TI - TTC25 Deficiency Results in Defects of the Outer Dynein Arm Docking Machinery and
Primary Ciliary Dyskinesia with Left-Right Body Asymmetry Randomization.
AB - Multiprotein complexes referred to as outer dynein arms (ODAs) develop the main
mechanical force to generate the ciliary and flagellar beat. ODA defects are the
most common cause of primary ciliary dyskinesia (PCD), a congenital disorder of
ciliary beating, characterized by recurrent infections of the upper and lower
airways, as well as by progressive lung failure and randomization of left-right
body asymmetry. Using a whole-exome sequencing approach, we identified recessive
loss-of-function mutations within TTC25 in three individuals from two unrelated
families affected by PCD. Mice generated by CRISPR/Cas9 technology and carrying a
deletion of exons 2 and 3 in Ttc25 presented with laterality defects.
Consistently, we observed immotile nodal cilia and missing leftward flow via
particle image velocimetry. Furthermore, transmission electron microscopy (TEM)
analysis in TTC25-deficient mice revealed an absence of ODAs. Consistent with our
findings in mice, we were able to show loss of the ciliary ODAs in humans via TEM
and immunofluorescence (IF) analyses. Additionally, IF analyses revealed an
absence of the ODA docking complex (ODA-DC), along with its known components
CCDC114, CCDC151, and ARMC4. Co-immunoprecipitation revealed interaction between
the ODA-DC component CCDC114 and TTC25. Thus, here we report TTC25 as a new
member of the ODA-DC machinery in humans and mice.
PMID- 27486781
TI - Isolated and Syndromic Retinal Dystrophy Caused by Biallelic Mutations in RCBTB1,
a Gene Implicated in Ubiquitination.
AB - Inherited retinal dystrophies (iRDs) are a group of genetically and clinically
heterogeneous conditions resulting from mutations in over 250 genes. Here,
homozygosity mapping and whole-exome sequencing (WES) in a consanguineous family
revealed a homozygous missense mutation, c.973C>T (p.His325Tyr), in RCBTB1. In
affected individuals, it was found to segregate with retinitis pigmentosa (RP),
goiter, primary ovarian insufficiency, and mild intellectual disability.
Subsequent analysis of WES data in different cohorts uncovered four additional
homozygous missense mutations in five unrelated families in whom iRD segregates
with or without syndromic features. Ocular phenotypes ranged from typical RP
starting in the second decade to chorioretinal dystrophy with a later age of
onset. The five missense mutations affect highly conserved residues either in the
sixth repeat of the RCC1 domain or in the BTB1 domain. A founder haplotype was
identified for mutation c.919G>A (p.Val307Met), occurring in two families of
Mediterranean origin. We showed ubiquitous mRNA expression of RCBTB1 and
demonstrated predominant RCBTB1 localization in human inner retina. RCBTB1 was
very recently shown to be involved in ubiquitination, more specifically as a CUL3
substrate adaptor. Therefore, the effect on different components of the CUL3 and
NFE2L2 (NRF2) pathway was assessed in affected individuals' lymphocytes,
revealing decreased mRNA expression of NFE2L2 and several NFE2L2 target genes. In
conclusion, our study puts forward mutations in RCBTB1 as a cause of autosomal
recessive non-syndromic and syndromic iRD. Finally, our data support a role for
impaired ubiquitination in the pathogenetic mechanism of RCBTB1 mutations.
PMID- 27486784
TI - Syndrome of Hepatic Cirrhosis, Dystonia, Polycythemia, and Hypermanganesemia
Caused by Mutations in SLC30A10, a Manganese Transporter in Man.
PMID- 27486783
TI - Mutations in DNAJB13, Encoding an HSP40 Family Member, Cause Primary Ciliary
Dyskinesia and Male Infertility.
AB - Primary ciliary dyskinesia (PCD) is an autosomal-recessive disease due to
functional or ultra-structural defects of motile cilia. Affected individuals
display recurrent respiratory-tract infections; most males are infertile as a
result of sperm flagellar dysfunction. The great majority of the PCD-associated
genes identified so far encode either components of dynein arms (DAs), which are
multiprotein-ATPase complexes essential for ciliary motility, or proteins
involved in DA assembly. To identify the molecular basis of a PCD phenotype
characterized by central complex (CC) defects but normal DA structure, a
phenotype found in ~15% of cases, we performed whole-exome sequencing in a male
individual with PCD and unexplained CC defects. This analysis, combined with
whole-genome SNP genotyping, identified a homozygous mutation in DNAJB13
(c.833T>G), a gene encoding a HSP40 co-chaperone whose ortholog in the
flagellated alga Chlamydomonas localizes to the radial spokes. In vitro studies
showed that this missense substitution (p.Met278Arg), which involves a highly
conserved residue of several HSP40 family members, leads to protein instability
and triggers proteasomal degradation, a result confirmed by the absence of
endogenous DNAJB13 in cilia and sperm from this individual. Subsequent DNAJB13
analyses identified another homozygous mutation in a second family; the study of
DNAJB13 transcripts obtained from airway cells showed that this mutation
(c.68+1G>C) results in a splicing defect consistent with a loss-of-function
mutation. Overall, this study, which establishes mutations in DNAJB13 as a cause
of PCD, unveils the key role played by DNAJB13 in the proper formation and
function of ciliary and flagellar axonemes in humans.
PMID- 27486782
TI - Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits and
Reveals a Role for Alternative GFI1B Splice Variants in Human Hematopoiesis.
AB - Circulating blood cell counts and indices are important indicators of
hematopoietic function and a number of clinical parameters, such as blood oxygen
carrying capacity, inflammation, and hemostasis. By performing whole-exome
sequence association analyses of hematologic quantitative traits in 15,459
community-dwelling individuals, followed by in silico replication in up to 52,024
independent samples, we identified two previously undescribed coding variants
associated with lower platelet count: a common missense variant in CPS1
(rs1047891, MAF = 0.33, discovery + replication p = 6.38 * 10(-10)) and a rare
synonymous variant in GFI1B (rs150813342, MAF = 0.009, discovery + replication p
= 1.79 * 10(-27)). By performing CRISPR/Cas9 genome editing in hematopoietic cell
lines and follow-up targeted knockdown experiments in primary human hematopoietic
stem and progenitor cells, we demonstrate an alternative splicing mechanism by
which the GFI1B rs150813342 variant suppresses formation of a GFI1B isoform that
preferentially promotes megakaryocyte differentiation and platelet production.
These results demonstrate how unbiased studies of natural variation in blood cell
traits can provide insight into the regulation of human hematopoiesis.
PMID- 27486786
TI - In Silico Design of Halogen-Bonding-Based Organocatalyst for Diels-Alder
Reaction, Claisen Rearrangement, and Cope-Type Hydroamination.
AB - Using DFT calculations, we investigated the use of halogen bonding (XB)
interactions to accelerate and control organic reactions, namely Diels-Alder
reaction, Claisen rearrangement, and Cope-type hydroamination. Our designed
triarylbenzene tripodal organocatalyst is characterized by three halogen bond
donors, perfluoro-iodophenyl groups. The calculated transition states unravel
multiple halogen bonds between the iodine atoms and various types of halogen bond
acceptors (lone pair, pi and sigma bonds). These cooperative noncovalent
interactions provide efficient binding between the catalyst and substrate (~15
kcal/mol binding energy) and are the key factors for transition-state
stabilization and molecular recognition. On the basis of our DFT calculations and
calculated turnover frequencies, the XB-catalyzed reactions are found to be
competitive with the corresponding hydrogen bonding catalysis reported in
literature.
PMID- 27486785
TI - Microfluidic Synthesis and Biological Evaluation of Photothermal Biodegradable
Copper Sulfide Nanoparticles.
AB - The continuous synthesis of biodegradable photothermal copper sulfide
nanoparticles has been carried out with the aid of a microfluidic platform. A
comparative physicochemical characterization of the resulting products from the
microreactor and from a conventional batch reactor has been performed. The
microreactor is able to operate in a continuous manner and with a 4-fold
reduction in the synthesis times compared to that of the conventional batch
reactor producing nanoparticles with the same physicochemical requirements.
Biodegradation subproducts obtained under simulated physiological conditions have
been identified, and a complete cytotoxicological analysis on different cell
lines was performed. The photothermal effect of those nanomaterials has been
demonstrated in vitro as well as their ability to generate reactive oxygen
species.
PMID- 27486787
TI - Correction to Discovery of a Potent and Selective Coactivator Associated Arginine
Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening.
PMID- 27486788
TI - Chiral Perylene Materials by Ionic Self-Assembly.
AB - Two chiral complexes (1-SDS and 1-SDBS) were prepared via the ionic self-assembly
of a chiral perylene diimide tecton with oppositely charged surfactants. The
effect of surfactant tail architecture on the self-assembly properties and
supramolecular structure was investigated in detail using UV-vis, IR, circular
dichroism, light microscopy, X-ray diffraction studies, and electron microscopy.
The results obtained revealed the molecular chirality of the parent perylene
tecton could be translated into supramolecular helical chirality of the resulting
complexes via primary ionic interactions through careful choice of solvent and
concentration. Differing solvent-dependent aggregation behavior was observed for
these complexes as a result of the different possible noncovalent interactions
via the surfactant alkyl tails. The results presented in this study demonstrate
that ionic self-assembly (ISA) is a facile strategy for the production of chiral
supramolecular materials based on perylene diimides. The structure-function
relationship is easily explored here due to the wide selection and easy
availability of common surfactants.
PMID- 27486789
TI - State-to-State Mode Specificity in F + CHD3 -> HF/DF + CD3/CHD2 Reaction.
AB - The F + CHD3 -> HF/DF + CD3/CHD2 reaction is studied using a state-to-state quasi
classical trajectory method on a recently developed ab initio based full
dimensional potential energy surface. Consistent with sudden vector projection
model predictions, the HF/DF products are highly excited in both vibrational and
rotational modes, while the CD3/CHD2 product internal excitation is mostly in the
umbrella/out-of-plane mode. Furthermore, the C-H stretching vibration in the CHD3
reactant is found to behave as an active mode for the HF + CD3 channel, leading
to additional excitation in the HF product but having almost no impact on CD3
vibrational state distributions. On the other hand, this mode acts as a spectator
for the DF + CHD2 channel, exerting little influence on the DF and other CHD2
vibrational modes except an extra quantum excitation in the C-H stretching mode.
The calculated vibrational state resolved differential cross sections are in good
agreement with available experimental results at Ec = 9.00 kcal/mol.
PMID- 27486790
TI - Construction of Covalent Organic Nanotubes by Light-Induced Cross-Linking of
Diacetylene-Based Helical Polymers.
AB - Organic nanotubes (ONTs) are tubular nanostructures composed of small molecules
or macromolecules that have found various applications including ion
sensor/channels, gas absorption, and photovoltaics. While most ONTs are
constructed by self-assembly processes based on weak noncovalent interactions,
this unique property gives rise to the inherent instability of their tubular
structures. Herein, we report a simple "helix-to-tube" strategy to construct
robust, covalent ONTs from easily accessible poly(m-phenylene diethynylene)s
(poly-PDEs) possessing chiral amide side chains that can adopt a helical
conformation through hydrogen-bonding interactions. The helically folded poly
PDEs subsequently undergo light-induced cross-linking at longitudinally aligned
1,3-butadiyne moieties across the whole helix to form covalent tubes (ONTs) both
in solution and solid phases. The structures of poly-PDEs and covalent ONTs were
characterized by spectroscopic analyses, diffraction analysis, and microscopic
analyses. We envisage that this simple yet powerful "helix-to-tube" strategy will
generate a range of ONT-based materials by introducing functional moieties into a
monomer.
PMID- 27486791
TI - Unexpected Ring Expansion of a Four-Membered Cyclophosphazane.
AB - Nucleophilic substitution reactions of the N(R),N(R)-spiro-bridged
octachlorobis(cyclotriphosphazene), N3P3Cl4[N(CH2)5CH3]2N3P3Cl4 (1), with sodium
salts of alcohols (1,3-propanediol, 2,2,3,3,4,4-hexafluoro-1,5-pentanediol, and
phenol) give ansa products (2-4) via an unexpected rearrangement. These products
were characterized by elemental analysis, mass spectrometry, and (1)H and (31)P
NMR spectroscopy. The molecular structures of compounds 3 and 4 were also
established by X-ray crystallography. This new class of phosphazene structures
consists of three fused P3N3 rings that arise from expansion of the four-membered
phosphazane ring in 1 to a six-membered N3P3 ring during alcoholysis reactions.
PMID- 27486792
TI - Aryne Compatible Solvents are not Always Innocent.
AB - Arynes are important and versatile intermediates in a variety of transformations.
Commonly used solvents for aryne chemistry include acetonitrile and
dichloromethane. Although rarely reported, the reactive nature of aryne
intermediates makes them prone to side reactions, which sometimes involve solvent
participation. Acetonitrile and dichloromethane are not always innocent solvents
and can participate in aryne-based reactions. These results are presented in the
context of ongoing mechanistic investigations of the triple aryne-tetrazine
reaction.
PMID- 27486793
TI - LI-RADS-CEUS - Proposal for a Contrast-Enhanced Ultrasound Algorithm for the
Diagnosis of Hepatocellular Carcinoma in High-Risk Populations.
AB - Purpose: To develop a contrast-enhanced ultrasound algorithm (LI-RADS-CEUS =
liver imaging reporting and data system with contrast-enhanced ultrasound) for
the diagnosis of hepatocellular carcinoma (HCC) in patients at risk. Materials
and Methods: A CEUS algorithm (LI-RADS-CEUS) was designed analogously to CT- and
MRI-based LI-RADS. LI-RADS-CEUS was evaluated retrospectively in 50 patients at
risk with confirmed HCC or non-HCC lesions (test group) with subsequent
validation in a prospective cohort of 50 patients (validation group). Results
were compared to histology, CE-CT and CE-MRI as reference standards. Results:
Tumor diagnosis in the test group/validation group (n = 50/50) were 46/41 HCCs,
3/3 intrahepatic cholangiocellular carcinomas (ICCs) and 1/6 benign lesions. The
diagnostic accuracy of LI-RADS-CEUS for HCC, ICC and non-HCC-non-ICC-lesions was
89 %. For the diagnosis of HCC, the diagnostic accuracy was 93.5 % (43/46 cases)
in the test group and 95.1 % (39/41 cases) in the validation group. The
sensitivity, specificity, positive predictive value (PPV) and negative predictive
value (NPV) were 94.3 %, 66.6 %, 94.3 % and 66.6 %, respectively (mean values
from both cohorts). Histological findings of HCC were available in 40 versus 23
cases (in total: G1 / G2/G3: 15/35/13). Arterial hyperenhancement was seen in
68/87 (78.2 %) of HCCs. Arterial hyperenhancement with subsequent portal venous
or late phase hypoenhancement was seen in 66 % of HCCs. Conclusion: LI-RADS-CEUS
offers a CEUS algorithm for standardized assessment and reporting of focal liver
lesions in patients at risk for HCC. Arterial hyperenhancement in CEUS is the key
feature for the diagnosis of HCC in patients at risk, whereas washout is not a
necessary prerequisite.
PMID- 27486794
TI - High Spatial Inhomogeneity in the Intima-Media Thickness of the Common Carotid
Artery is Associated with a Larger Degree of Stenosis in the Internal Carotid
Artery: The PARISK Study.
AB - Purpose Inhomogeneity of arterial wall thickness may be indicative of distal
plaques. This study investigates the intra-subject association between relative
spatial intima-media thickness (IMT) inhomogeneity of the common carotid artery
(CCA) and the degree of stenosis of plaques in the internal carotid artery (ICA).
Materials and Methods We included 240 patients with a recent ischemic stroke or
transient ischemic attack and mild-to-moderate stenosis in the ipsilateral ICA.
IMT inhomogeneity was extracted from B-mode ultrasound recordings. The degree of
ICA stenosis was assessed on CT angiography according to the European Carotid
Surgery Trial method. Patients were divided into groups with a low (<= 2 %) and a
high (> 2 %) IMT inhomogeneity scaled with respect to the local end-diastolic
diameter. Results 182 patients had suitable CT and ultrasound measurements.
Relative CCA-IMT inhomogeneity was similar for the symptomatic and asymptomatic
side (difference: 0.02 %, p = 0.85). High relative IMT inhomogeneity was
associated with a larger IMT (difference: 235 um, p < 0.001) and larger degree of
ICA stenosis (difference: 5 %, p = 0.023) which remained significant (p = 0.016)
after adjustment for common risk factors. Conclusion Regardless of common risk
factors, high relative CCA-IMT inhomogeneity is associated with a greater degree
of ICA stenosis and is therefore indicative of atherosclerotic disease. The
predictive value of CCA-IMT inhomogeneity for plaque progression and recurrence
of cerebrovascular symptoms will be determined in the follow-up phase of PARISK.
PMID- 27486795
TI - Transcranial Sonography of the Insula: Digitized Image Analysis of Fusion Images
with Magnetic Resonance.
AB - Purpose: Transcranial B-mode sonography (TCS) of brain parenchyma is increasingly
used as a diagnostic tool for movement disorders. Accordingly, experimental B
Mode Assist software was developed to enable digitized analysis of the
echogenicity of predefined brain regions. The aim of the study was to assess the
reproducibility of digitized TCS image analysis of the insula. Materials and
Methods: A total of 130 patients with an indication for neurosonological
examination were screened for participation in the study. The insula was imaged
from the right temporal bone window using Virtual Navigator and TCS-MRI (magnetic
resonance imaging) fusion imaging. All subjects were examined three times by two
experienced sonographers. Corresponding images of the insula in the axial
thalamic plane were encoded and digitally analyzed. Interclass correlation
coefficient (ICC) and Spearman's rank correlation coefficient were used for the
assessment of intra- and inter-reader as well as intra- and inter-investigator
reliabilities. Results: TCS images of 114 patients were evaluated (21 patients
with TIA, 53 patients with headache, 18 patients with essential tremor, 22
patients with neurodegerative disease). 16 patients were excluded from analysis
due to insufficient bone window. The intra-reader, inter-reader, intra
investigator and inter-investigator ICCs/Spearman's rank correlation coefficients
were 0.995/0.993, 0.937/0.921, 0.969/0.961 and 0.875/0.858, resp. Conclusion: The
present study demonstrates a high reliability to reproduce echogenicity values of
the insula using digitized image analysis and TCS-MRI fusion images with almost
perfect intra-reader, inter-reader, intra-investigator and inter-investigator
agreement.
PMID- 27486796
TI - Live-Cell Bioorthogonal Chemical Imaging: Stimulated Raman Scattering Microscopy
of Vibrational Probes.
AB - Innovations in light microscopy have tremendously revolutionized the way
researchers study biological systems with subcellular resolution. In particular,
fluorescence microscopy with the expanding choices of fluorescent probes has
provided a comprehensive toolkit to tag and visualize various molecules of
interest with exquisite specificity and high sensitivity. Although fluorescence
microscopy is currently the method of choice for cellular imaging, it faces
fundamental limitations for studying the vast number of small biomolecules. This
is because common fluorescent labels, which are relatively bulky, could introduce
considerable perturbation to or even completely alter the native functions of
vital small biomolecules. Hence, despite their immense functional importance,
these small biomolecules remain largely undetectable by fluorescence microscopy.
To address this challenge, a bioorthogonal chemical imaging platform has recently
been introduced. By coupling stimulated Raman scattering (SRS) microscopy, an
emerging nonlinear Raman microscopy technique, with tiny and Raman-active
vibrational probes (e.g., alkynes and stable isotopes), bioorthogonal chemical
imaging exhibits superb sensitivity, specificity, and biocompatibility for
imaging small biomolecules in live systems. In this Account, we review recent
technical achievements for visualizing a broad spectrum of small biomolecules,
including ribonucleosides and deoxyribonucleosides, amino acids, fatty acids,
choline, glucose, cholesterol, and small-molecule drugs in live biological
systems ranging from individual cells to animal tissues and model organisms.
Importantly, this platform is compatible with live-cell biology, thus allowing
real-time imaging of small-molecule dynamics. Moreover, we discuss further
chemical and spectroscopic strategies for multicolor bioorthogonal chemical
imaging, a valuable technique in the era of "omics". As a unique tool for
biological discovery, this platform has been applied to studying various
metabolic processes under both physiological and pathological states, including
protein synthesis activity of neuronal systems, protein aggregations in
Huntington disease models, glucose uptake in tumor xenografts, and drug
penetration through skin tissues. We envision that the coupling of SRS microscopy
with vibrational probes would do for small biomolecules what fluorescence
microscopy of fluorophores has done for larger molecular species.
PMID- 27486797
TI - NMR Study Reveals the Receiver Domain of Arabidopsis ETHYLENE RESPONSE1 Ethylene
Receptor as an Atypical Type Response Regulator.
AB - The gaseous plant hormone ethylene, recognized by plant ethylene receptors, plays
a pivotal role in various aspects of plant growth and development. ETHYLENE
RESPONSE1 (ETR1) is an ethylene receptor isolated from Arabidopsis and has a
structure characteristic of prokaryotic two-component histidine kinase (HK) and
receiver domain (RD), where the RD structurally resembles bacteria response
regulators (RRs). The ETR1 HK domain has autophosphorylation activity, and little
is known if the HK can transfer the phosphoryl group to the RD for receptor
signaling. Unveiling the correlation of the receptor structure and
phosphorylation status would advance the studies towards the underlying
mechanisms of ETR1 receptor signaling. In this study, using the nuclear magnetic
resonance technique, our data suggested that the ETR1-RD is monomeric in solution
and the rigid structure of the RD prevents the conserved aspartate residue
phosphorylation. Comparing the backbone dynamics with other RRs, we propose that
backbone flexibility is critical to the RR phosphorylation. Besides the limited
flexibility, ETR1-RD has a unique gamma loop conformation of opposite
orientation, which makes ETR1-RD unfavorable for phosphorylation. These two
features explain why ETR1-RD cannot be phosphorylated and is classified as an
atypical type RR. As a control, phosphorylation of the ETR1-RD was also impaired
when the sequence was swapped to the fragment of the bacterial typical type RR,
CheY. Here, we suggest a molecule insight that the ETR1-RD already exists as an
active formation and executes its function through binding with the downstream
factors without phosphorylation.
PMID- 27486798
TI - Molecular Identification of Hookworm Isolates in Humans, Dogs and Soil in a
Tribal Area in Tamil Nadu, India.
AB - BACKGROUND: Hookworms (Necator americanus and Ancylostoma duodenale) remain a
major public health problem worldwide. Infections with hookworms (e.g., A.
caninum, A. ceylanicum and A. braziliense) are also prevalent in dogs, but the
role of dogs as a reservoir for zoonotic hookworm infections in humans needs to
be further explored. METHODOLOGY/PRINCIPAL FINDINGS: As part of an open-label
community based cluster-randomized trial in a tribal area in Tamil Nadu (India;
2013-2015), a total of 143 isolates of hookworm eggs from human stool were
speciated based on a previously described PCR-RFLP methodology. The presence of
hookworm DNA was confirmed in 119 of 143 human samples. N. americanus (100%) was
the most prevalent species, followed by A. caninum (16.8%) and A. duodenale
(8.4%). Because of the high prevalence of A. caninum in humans, dog samples were
also collected to assess the prevalence of A. caninum in dogs. In 68 out of 77
canine stool samples the presence of hookworms was confirmed using PCR-RFLP. In
dogs, both A. caninum (76.4%) and A. ceylanicum (27.9%) were identified.
Additionally, to determine the contamination of soil with zoonotic hookworm
larvae, topsoil was collected from defecating areas. Hookworm DNA was detected in
72 out of 78 soil samples that revealed presence of hookworm-like nematode
larvae. In soil, different hookworm species were identified, with animal
hookworms being more prevalent (A. ceylanicum: 60.2%, A. caninum: 29.4%, A.
duodenale: 16.6%, N. americanus: 1.4%, A. braziliense: 1.4%).
CONCLUSIONS/SIGNIFICANCE: In our study we regularly detected the presence of A.
caninum DNA in the stool of humans. Whether this is the result of infection is
currently unknown but it does warrant a closer look at dogs as a potential
reservoir.
PMID- 27486799
TI - Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant
Male Mice.
AB - After using a self-inactivating lentivirus for non-targeted insertional
mutagenesis in mice, we identified a transgenic family with a recessive mutation
that resulted in reduced fertility in homozygous transgenic mice. The lentiviral
integration site was amplified by inverse PCR. Sequencing revealed that
integration had occurred in intron 8 of the mouse Fance gene, which encodes the
Fanconi anemia E (Fance) protein. Fanconi anemia (FA) proteins play pivotal roles
in cellular responses to DNA damage and Fance acts as a molecular bridge between
the FA core complex and Fancd2. To investigate the reduced fertility in the
mutant males, we analyzed postnatal development of testicular germ cells. At one
week after birth, most tubules in the mutant testes contained few or no germ
cells. Over the next 2-3 weeks, germ cells accumulated in a limited number of
tubules, so that some tubules contained germ cells around the full periphery of
the tubule. Once sufficient numbers of germ cells had accumulated, they began to
undergo the later stages of spermatogenesis. Immunoassays revealed that the
Fancd2 protein accumulated around the periphery of the nucleus in normal
developing spermatocytes, but we did not detect a similar localization of Fancd2
in the Fance mutant testes. Our assays indicate that although Fance mutant males
are germ cell deficient at birth, the extant germ cells can proliferate and, if
they reach a threshold density, can differentiate into mature sperm. Analogous to
previous studies of FA genes in mice, our results show that the Fance protein
plays an important, but not absolutely essential, role in the initial
developmental expansion of the male germ line.
PMID- 27486800
TI - Transcriptome Analysis of Storage Roots and Fibrous Roots of the Traditional
Medicinal Herb Callerya speciosa (Champ.) ScHot.
AB - Callerya speciosa (Champ.) ScHot is a woody perennial plant in Fabaceae, the
roots of which are used medicinally. The storage roots of C. speciosa are derived
from fibrous roots, but not all fibrous roots can develop into storage roots. To
detect key genes involved in storage roots formation, we performed Illumina
sequencing of the C. speciosa storage roots and fibrous roots. De novo assembly
resulted in 161,926 unigenes, which were subsequently annotated by BLAST, GO and
KEGG analyses. After expression profiling, 4538 differentially expressed genes
were identified. The KEGG pathway enrichment analysis revealed changes in the
biosynthesis of cytokinin, phenylpropanoid, starch, sucrose, flavone and other
secondary metabolites. Transcription factor-related differentially expressed
genes (DEGs) were also identified, including such gene families as GRAS, COL,
MIKC, ERF, LBD, and NAC. The DEGs related to light signaling, starch, sugar,
photohormones and cell wall-loosening might be involved in the formation of
storage roots. This study provides the first transcriptome profiling of C.
speciosa roots, data that will facilitate future research of root development and
metabolites with medicinal value as well as the breeding of C. speciosa.
PMID- 27486801
TI - Frequency- and Phase Encoded SSVEP Using Spatiotemporal Beamforming.
AB - In brain-computer interfaces (BCIs) based on steady-state visual evoked
potentials (SSVEPs) the number of selectable targets is rather limited when each
target has its own stimulation frequency. One way to remedy this is by combining
frequency- with phase encoding. We introduce a new multivariate spatiotemporal
filter, based on Linearly Constrained Minimum Variance (LCMV) beamforming, for
discriminating between frequency-phase encoded targets more accurately, even when
using short signal lengths than with (extended) Canonical Correlation Analysis
(CCA), which is traditionally posited for this stimulation paradigm.
PMID- 27486802
TI - Does Grammatical Structure Accelerate Number Word Learning? Evidence from
Learners of Dual and Non-Dual Dialects of Slovenian.
AB - How does linguistic structure affect children's acquisition of early number word
meanings? Previous studies have tested this question by comparing how children
learning languages with different grammatical representations of number learn the
meanings of labels for small numbers, like 1, 2, and 3. For example, children who
acquire a language with singular-plural marking, like English, are faster to
learn the word for 1 than children learning a language that lacks the singular
plural distinction, perhaps because the word for 1 is always used in singular
contexts, highlighting its meaning. These studies are problematic, however,
because reported differences in number word learning may be due to unmeasured
cross-cultural differences rather than specific linguistic differences. To
address this problem, we investigated number word learning in four groups of
children from a single culture who spoke different dialects of the same language
that differed chiefly with respect to how they grammatically mark number. We
found that learning a dialect which features "dual" morphology (marking of pairs)
accelerated children's acquisition of the number word two relative to learning a
"non-dual" dialect of the same language.
PMID- 27486803
TI - Two New Mylagaulid Rodents from the Early Miocene of China.
AB - Mylagaulid fossorial rodents are a common component of North American Miocene
fossil faunas. However outside of North America, only three species are known
from Asia. Here we report two new mylagaulids, Irtyshogaulus minor gen. et sp.
nov. and Irtyshogaulus major gen. et sp. nov., recovered from early Miocene
sediments in the Junggar Basin in northwestern China. The two new taxa are small
sized, high-crowned promylagauline rodents. Their lower molars possess high
metastylid crests, small mesostylids, broad and posterolingually expanded labial
inflections, and transversely extending metalophid IIs. The mesoconid is absent
in both species. The anterior and posterior fossettids are large and equally
developed. Their upper M1-2s possess a square occlusal surface with five deep
fossettes. The two new taxa are distinguished from each other mainly by their
size, the morphology of fossettes and fossettids, development of mesial and
distal lophs, posterior reduction of M3, and the orientation of m2 hypolophid.
Our phylogenetic analysis indicates that Irtyshogaulus and Lamugaulus (another
early Miocene Asian mylagaulid) are sister taxa. The two genera are nested among
the North American promylagaulines, and share a common ancestor from North
America, indicating early Miocene intercontinental dispersal within this clade of
rodents.
PMID- 27486804
TI - The Incremental Prognostic Value of Cardiac Computed Tomography in Comparison
with Single-Photon Emission Computed Tomography in Patients with Suspected
Coronary Artery Disease.
AB - BACKGROUND: Coronary computed tomographic angiography (CCTA) facilitates
comprehensive evaluation of coronary artery disease (CAD), including plaque
characterization, and can provide additive diagnostic value to single-photon
emission computed tomography (SPECT). However, data regarding the incremental
prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and
incremental prognostic value of CCTA, as compared with clinical risk factors and
SPECT. MATERIALS AND METHODS: A total of 1,077 patients with suspected CAD who
underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled
retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed
stress score were evaluated on SPECT. Presence, extent of coronary
atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque
composition was categorized as non-calcified, mixed, or calcified according to
the volume of calcified component (>130 Hounsfield Units). Patients were followed
up for the occurrence of adverse cardiac events including cardiac death, non
fatal myocardial infarction, unstable angina, and late revascularization (>90
days after imaging studies). RESULTS: During follow-up (median 23 months),
adverse cardiac events were observed in 71 patients (6.6%). When adjusted for
clinical risk factors and SPECT findings, the presence of any coronary plaque,
any plaque in >=3 segments, coronary artery calcium score (CACS) >=400, a plaque
>=50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP
in >=2 segments were independent predictors of adverse cardiac events; however,
the presence of calcified plaque (CP) was not. Conventional CCTA findings,
including CACS >=400 and a plaque >=50% DS, demonstrated incremental prognostic
value over clinical risk factors and SPECT (chi2 54.19 to 101.03; p <0.001).
Addition of NCP/MP in >=2 segments resulted in further significantly improved
prediction (chi2 101.03 to 113.29; p <0.001). CONCLUSION: Comprehensive CCTA
evaluation of coronary atherosclerosis provides independent and incremental
prognostic value in relation to SPECT evaluation of myocardial ischemia.
Specifically, segmentally-analyzed plaque composition with CCTA provides further
risk stratification in addition to CACS and DS.
PMID- 27486805
TI - Regulatory Cytokine Expression and Preterm Birth: Case-Control Study Nested in a
Cohort.
AB - BACKGROUND: Currently known risk factors explain only a small fraction of preterm
birth (PTB). Previous PTB is one of the most important predictors. However, this
information is not available in primiparous women. Few studies have looked at
associations between regulatory cytokine expression (RCE) and PTB and the results
are conflicting. OBJECTIVE: To investigate the association of RCE-Interleukin 10
(IL-10) and Transforming Growth Factor beta (TGF-beta)-with PTB, and to assess
whether bacterial vaginosis (BV) is involved in this relationship. METHODS: This
was a case-control study nested in a prospective cohort-called BRISA. Women with
singleton pregnancies were interviewed from 22 to 25 weeks of gestational age
(GA). Women were recruited from health services in Sao Luis, Brazil. A blood
sample was collected and gynecological examination was performed. Serum IL-10 and
TGF-beta were determined using cytometric bead array. Nugent score >7 and/or the
presence of clue cells were used for BV diagnosis. All PTB estimated by
ultrasound dating performed before 20 weeks of gestational age were considered
cases. Controls were selected by simple random sampling from the rest of the
cohort, at a 2:1 ratio. Different models were tested, according to the main
independent variable. Odds ratios (OR) and 95% confidence intervals (95%CI) were
estimated by regression analyses. RESULTS: The study included 327 pregnant women,
109 cases and 218 controls. No associations were found between BV and PTB (P =
1.44; 95%CI: 0.51-3.77). Low levels of IL-10 (OR = 2.92 95%CI: 1.38-6.16) or TGF
beta (OR = 16.90 95%CI: 6.42-44.51) or both simultaneously (OR = 77.16 95%CI:
7.99-744.88) were associated with increasing odds of PTB, even after adjustment
for confounding. CONCLUSION: Decreased RCE is a risk factor for PTB. This
relationship, however, is not triggered by the presence of BV. Low IL-10/TGF-beta
levels from 22 to 25 weeks of GA could be used as early predictors of PTB. We
suggest monitoring of these RCE, especially among primiparous women, for whom
history of previous PTB is not available.
PMID- 27486807
TI - Preparation and evaluation of enteric coated tablets of hot-melt extruded
lansoprazole.
AB - The objective of this work was to use hot-melt extrusion (HME) technology to
improve the physiochemical properties of lansoprazole (LNS) to prepare stable
enteric coated LNS tablets. For the extrusion process, we chose Kollidon(r) 12 PF
(K12) polymeric matrix. Lutrol(r) F 68 was selected as the plasticizer and
magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10%
drug load was extruded with K12 and F68. LNS changed to the amorphous phase and
showed better release compared to that of the pure crystalline drug. Inclusion of
MgO improved LNS extrudability and release and resulted in over 80% drug release
in the buffer stage. Hot-melt extruded LNS was physically and chemically stable
after 12 months of storage. Both formulations were studied for compatibility with
Eudragit(r) L100-55. The optimized formulation was compressed into a tablet
followed by coating process utilizing a pan coater using L100-55 as an enteric
coating polymer. In a two-step dissolution study, the release profile of the
enteric coated LNS tablets in the acidic stage was less than 10% of the LNS,
while that in the buffer stage was more than 80%. Drug content analysis revealed
the LNS content to be 97%, indicating the chemical stability of the enteric
coated tablet after storage for six months. HME, which has not been previously
used for LNS, is a valuable technique to reduce processing time in the
manufacture of enteric coated formulations of an acid-sensitive active
pharmaceutical ingredient as compared to the existing methods.
PMID- 27486808
TI - Rapid Intracranial Response to Osimertinib in a Patient with Epidermal Growth
Factor Receptor T790M-Positive Adenocarcinoma of the Lung.
AB - BACKGROUND: Osimertinib (AZD9291, Tagrisso) is a potent, irreversible third
generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
(TKI). CASE REPORT: Our report demonstrates that osimertinib is able to inhibit
the growth of a radiotherapy- and surgery-refractory EGFR T790M-positive brain
metastasis in a patient with lung adenocarcinoma. CONCLUSION: These data show
that re-biopsy in EGFR-mutated non-small cell lung cancer patients with acquired
TKI resistance should be performed.
PMID- 27486806
TI - New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension
in Humans.
AB - Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack
of specific clinical symptoms and biomarkers, especially at early stages. We
compared plasma metabolic fingerprints of PAH patients (n = 20) with matched
healthy volunteers (n = 20) using, for the first time, untargeted multiplatform
metabolomics approach consisting of high-performance liquid and gas
chromatography coupled with mass spectrometry. Multivariate statistical analyses
were performed to select metabolites that contribute most to groups'
classification (21 from liquid in both ionization modes and 9 from gas
chromatography-mass spectrometry). We found metabolites related to energy
imbalance, such as glycolysis-derived metabolites, as well as metabolites
involved in fatty acid, lipid and amino acid metabolism. We observed
statistically significant changes in threitol and aminomalonic acid in PAH
patients, which could provide new biochemical insights into the pathogenesis of
the disease. The results were externally validated on independent case and
control cohorts, confirming up to 16 metabolites as statistically significant in
the validation study. Multiplatform metabolomics, followed by multivariate
chemometric data analysis has a huge potential for explaining pathogenesis of PAH
and for searching potential and new more specific and less invasive markers of
the disease.
PMID- 27486809
TI - Possible Underlying Mechanisms of the Renoprotective Effect of Remote Limb
Ischemic Preconditioning Against Renal Ischemia/Reperfusion Injury: A Role of
Osteopontin, Transforming Growth Factor-Beta and Survivin.
AB - BACKGROUND: It has been documented that remote limb ischemic preconditioning
(rIPC) protect kidneys against renal ischemia/reperfusion (I/R). We hypothesized
that osteopontin (OPN), transforming growth factor beta (TGF-beta), apoptotic
proteins (survivin and caspase-3) and oxidative stress play role in the
renoprotective effects of rIPC. MATERIALS AND METHODS: Fifty-four male Sprague
Dawley rats were randomized into 3 equal groups: sham group, I/R group (left
renal 45 min ischemia) and rIPC group (as I/R group with 3 cycles of left hind
limb ischemia just before renal ischemia). Each group was subdivided into 24, 48
and 72 h groups according to the time of sacrifice. We measured serum creatinine
and blood urea nitrogen (BUN) at the baseline and end points. Also, left kidney
was harvested at study end points for assessment of the expression of OPN, TGF
beta, apoptotic proteins (survivin and caspase-3) and oxidative stress markers
(malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) in
kidney tissues and histopathological examination. RESULTS: Serum creatinine and
BUN levels and histopathological damage score were significantly lower in rIPC
group than I/R group (p < 0.005). Also, compared to I/R group, the levels of MDA
and the expression of OPN, TGF-beta and caspase-3 in kidney tissues were
significantly lower in rIPC group, while the levels of SOD and GSH and the
expression of survivin in kidney tissues were significantly higher in rIPC group
at all time points (p <= 0.05). CONCLUSIONS: rIPC exhibited protective effects
against renal I/R injury which might be due to inhibition of OPN expression,
inflammatory cytokine TGF-beta and caspase-3 and activation of anti-apoptotic
protein survivin as well as improvement of oxidative stress in kidney tissues.
PMID- 27486810
TI - Bilateral optic nerve edema presenting as initial manifestation of thyroid eye
disease.
AB - A 48-year-old smoker with a history of hyperthyroidism treated 10 years prior to
presentation with radioactive iodine ablation of the thyroid gland presented to
his ophthalmologist with a 2-week history of transient loss of vision in the
right eye occurring for 1 to 2 hours each morning. He denied ocular pain,
diplopia or change in the prominence of one or both eyes. Examination revealed 2
mm of relative proptosis on the right, bilateral temporal flare and lower lid
retraction. There was minimal upper lid retraction and no evidence of lid lag.
Ocular motility was full. Dilated fundoscopic examination revealed bilateral
optic nerve edema, right more than left. CT of the orbit demonstrated enlargement
of the extraocular muscles bilaterally with marked enlargement of the right
medial rectus and left inferior rectus muscles resulting in crowding at the
orbital apex bilaterally. Laboratory testing revealed the patient to be
hyperthyroid. The patient was treated with high dose oral steroids followed by
orbital radiation. Hyperthyroidism was managed by the patient's primary care
physician. Visual symptoms rapidly improved with oral steroids and orbital
radiation. Optic nerve edema completely resolved. Repeat CT imaging demonstrated
a reduction in the enlargement of the extraocular muscles with relief of
bilateral optic nerve compression.
PMID- 27486811
TI - Longitudinal Association between Child Emotion Regulation and Aggression, and the
Role of Parenting: A Comparison of Three Cultures.
AB - BACKGROUND: The ability to regulate emotions is a key developmental achievement
acquired during social interactions and associated with better behavioral and
social outcomes. We examined the influence of culture on child emotion regulation
(ER) and aggression and on early parenting practices, and the role of parenting
in child ER. METHODS: We assessed 48 mother-infant dyads from three cultures (1
UK, 2 South African) at infant age of 3 months for maternal sensitivity during
face-to-face interactions and responses to infant distress during daily life, and
at 2 years for child ER strategies and maternally reported aggression. RESULTS:
There were cultural differences in child ER, and these were associated with
differences in levels of aggression. Maternal strategies in response to early
infant distress also differed by culture and predicted later child ER. Maternal
sensitivity during face-to-face interactions was not associated with culture and
showed no clear relationship with child ER. CONCLUSION: Cultural differences in
maternal responses to infant distress mediated differences in child ER that are,
in turn, related to differences in child aggression.
PMID- 27486812
TI - A Meta-Analysis for Effects of Elevated Pre-Transplantation Serum Ferritin on the
Outcomes in Patients Undergoing Hematopoietic Stem Cell Transplantation.
AB - The level of pre-transplantation serum ferritin (SF) is one of the factors
related to outcome for patients undergoing allogeneic hematopoietic stem cell
transplantation. We searched PubMed and Cochrane Library databases from 2000 to
2014. The primary efficacy outcome was overall survival rate and non-relapse
mortality. Twenty clinical trials were selected from 189 studies identified. The
combined hazard ratio indicated a significantly lower overall survival rate and a
higher non-relapse mortality rate in patients with elevated SF before
transplantation. This indicates that elevated pre-transplantation SF affects
outcome in patients undergoing allogeneic hematopoietic stem cell
transplantation.
PMID- 27486814
TI - Nucleophosmin leukemogenic mutant activates Wnt signaling during zebrafish
development.
AB - Nucleophosmin (NPM1) is a ubiquitous multifunctional phosphoprotein with both
oncogenic and tumor suppressor functions. Mutations of the NPM1 gene are the most
frequent genetic alterations in acute myeloid leukemia (AML) and result in the
expression of a mutant protein with aberrant cytoplasmic localization, NPMc+.
Although NPMc+ causes myeloproliferation and AML in animal models, its mechanism
of action remains largely unknown. Here we report that NPMc+ activates canonical
Wnt signaling during the early phases of zebrafish development and determines a
Wnt-dependent increase in the number of progenitor cells during primitive
hematopoiesis. Coherently, the canonical Wnt pathway is active in AML blasts
bearing NPMc+ and depletion of the mutant protein in the patient derived OCI-AML3
cell line leads to a decrease in the levels of active beta-catenin and of Wnt
target genes. Our results reveal a novel function of NPMc+ and provide insight
into the molecular pathogenesis of AML bearing NPM1 mutations.
PMID- 27486815
TI - The human Smoothened inhibitor PF-04449913 induces exit from quiescence and loss
of multipotent Drosophila hematopoietic progenitor cells.
AB - The efficient treatment of hematological malignancies as Acute Myeloid Leukemia,
myelofibrosis and Chronic Myeloid Leukemia, requires the elimination of cancer
initiating cells and the prevention of disease relapse through targeting pathways
that stimulate generation and maintenance of these cells. In mammals, inhibition
of Smoothened, the key mediator of the Hedgehog signaling pathway, reduces
Chronic Myeloid Leukemia progression and propagation. These findings make Smo a
candidate target to inhibit maintenance of leukemia-initiating cells. In
Drosophila melanogaster the same pathway maintains the hematopoietic precursor
cells of the lymph gland, the hematopoietic organ that develops in the larva.
Using Drosophila as an in vivo model, we investigated the mode of action of PF
04449913, a small-molecule inhibitor of the human Smo protein. Drosophila larvae
fed with PF-04449913 showed traits of altered hematopoietic homeostasis. These
include the development of melanotic nodules, increase of circulating hemocytes,
the size increase of the lymph gland and accelerated differentiation of blood
cells likely due to the exit of multi-potent precursors from quiescence.
Importantly, the Smo inhibition can lead to the complete loss of hematopoietic
precursors. We conclude that PF-04449913 inhibits Drosophila Smo blocking the Hh
signaling pathway and causing the loss of hematopoietic precursor cells.
Interestingly, this is the effect expected in patients treated with PF-04449913:
number decrease of cancer initiating cells in the bone marrow to reduce the risk
of leukemia relapse. Altogether our results indicate that Drosophila comprises a
model system for the in vivo study of molecules that target evolutionary
conserved pathways implicated in human hematological malignancies.
PMID- 27486817
TI - Samarium-153-EDTMP (Quadramet(r)) with or without vaccine in metastatic
castration-resistant prostate cancer: A randomized Phase 2 trial.
AB - PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic
castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine
tetramethylene phosphonate (Sm-153-EDTMP; Quadramet(r)), a radiopharmaceutical,
binds osteoblastic bone lesions and emits beta particles causing local tumor cell
destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating
immune-mediated killing. This phase 2 multi-center trial randomized patients to
Sm-153-EDTMP alone or with PSA-TRICOM vaccine. Eligibility required mCRPC, bone
metastases, prior docetaxel and no visceral disease. The primary endpoint was the
proportion of patients without radiographic disease progression at 4 months.
Secondary endpoints included progression-free survival (PFS), overall survival
(OS), and immune responses. Forty-four patients enrolled. Eighteen and 21
patients were evaluable for the primary endpoint in Sm-153-EDTMP alone and
combination arms, respectively. There was no statistical difference in the
primary endpoint, with two of 18 (11.1%) and five of 21 (23.8%) in Sm-153-EDTMP
alone and combination arms, respectively, having stable disease at approximately
the 4-month evaluation time point (P = 0.27). Median PFS was 1.7 vs. 3.7 months
in the Sm-153-EDTMP alone and combination arms (P = 0.041, HR = 0.51, P = 0.046).
No patient in the Sm-153-EDTMP alone arm achieved prostate-specific antigen (PSA)
decline > 30% compared with four patients (of 21) in the combination arm,
including three with PSA decline > 50%. Toxicities were similar between arms and
related to number of Sm-153-EDTMP doses administered. These results provide the
rationale for clinical evaluation of new radiopharmaceuticals, such as Ra-223, in
combination with PSA-TRICOM.
PMID- 27486820
TI - TAM receptors Tyro3 and Mer as novel targets in colorectal cancer.
AB - PURPOSE: CRC remains the third most common cancer worldwide with a high 5-year
mortality rate in advanced cases. Combined with chemotherapy, targeted therapy is
an additional treatment option. However as CRC still escapes targeted therapy the
vigorous search for new targets is warranted to increase patients' overall
survival. RESULTS: In this study we describe a new role for Gas6/protein S-TAM
receptor interaction in CRC. Gas6, expressed by tumor-infiltrating M2-like
macrophages, enhances malignant properties of tumor cells including
proliferation, invasion and colony formation. Upon chemotherapy macrophages
increase Gas6 synthesis, which significantly attenuates the cytotoxic effect of 5
FU chemotherapy on tumor cells. The anti-coagulant protein S has similar effects
as Gas6.In CRC patient samples Tyro3 was overexpressed within the tumor. In-vitro
inhibition of Tyro3 and Mer reduces tumor cell proliferation and sensitizes tumor
cells to chemotherapy. Moreover high expression of Tyro3 and Mer in tumor tissue
significantly shortens CRC patients' survival. EXPERIMENTAL DESIGN: Various in
vitro models were used to investigate the role of Gas6 and its TAM receptors in
human CRC cells, by stimulation (rhGas6) and knockdown (siRNA) of Axl, Tyro3 and
Mer. In terms of a translational research, we additionally performed an
expression analysis in human CRC tissue and analyzed the medical record of these
patients. CONCLUSIONS: Tyro3 and Mer represent novel therapeutic targets in CRC
and warrant further preclinical and clinical investigation in the future.
PMID- 27486821
TI - Repurposing phenformin for the targeting of glioma stem cells and the treatment
of glioblastoma.
AB - Glioblastoma (GBM) is the most aggressive primary brain tumor with poor
prognosis. Here, we studied the effects of phenformin, a mitochondrial complex I
inhibitor and more potent chemical analog of the diabetes drug metformin on the
inhibition of cell growth and induction of apoptosis of glioma stem cells (GSCs)
using both in vitro and in vivo models. Phenformin inhibited the self-renewal of
GSCs, decreased the expression of stemness and mesenchymal markers and increased
the expression of miR-124, 137 and let-7. Silencing of let-7 abrogated phenformin
effects on the self-renewal of GSCs via a pathway associated with inhibition of
H19 and HMGA2 expression. Moreover, we demonstrate that phenformin inhibited
tumor growth and prolonged the overall survival of mice orthotopically
transplanted with GSCs. Combined treatments of phenformin and temozolomide
exerted an increased antitumor effect on GSCs in vitro and in vivo. In addition,
dichloroacetate, an inhibitor of the glycolysis enzyme pyruvate dehydrogenase
kinase, that decreases lactic acidosis induced by biguanides, enhanced phenformin
effects on the induction of cell death in GSCs and prolonged the survival of
xenograft-bearing mice. Our results demonstrate for the first time that
phenformin targets GSCs and can be efficiently combined with current therapies
for GBM treatment and GSC eradication.
PMID- 27486822
TI - Bone marrow involvement identifies a subgroup of advanced Ewing sarcoma patients
with fatal outcome irrespective of therapy in contrast to curable patients with
multiple bone metastases but unaffected marrow.
AB - PURPOSE: Advanced Ewing sarcomas have poor prognosis. They are defined by early
relapse (<24 months after diagnosis) and/or by metastasis to multiple bones or
bone marrow (BM). We analyzed risk factors, toxicity and survival in advanced
Ewing sarcoma patients treated with the MetaEICESS vs. EICESS92 protocols.
DESIGN: Of 44 patients, 18 patients were enrolled into two subsequent MetaEICESS
protocols between 1992 and 2014, and compared to outcomes of 26 advanced Ewing
sarcoma patients treated with EICESS 1992 between 1992 and 1996. MetaEICESS 1992
consisted of induction chemotherapy, whole body imaging directed radiotherapy to
the primary tumor and metastases, tandem high-dose chemotherapy and autologous
rescue. In MetaEICESS 2007 this treatment was complemented by allogeneic stem
cell transplantation. EICESS 1992 comprised induction chemotherapy, local therapy
to the primary tumor only followed by consolidation chemotherapy. RESULTS: In
MetaEICESS 8/18 patients survived in complete remission vs. 2/26 in EICESS 1992
(p<0.05). Survival did not differ between MetaEICESS 2007 and MetaEICESS 1992.
Three MetaEICESS patients died of complications, all in MetaEICESS 1992. After
exclusion of patients succumbing to treatment related complications (n=3), 7/10
patients survived without BM involvement, in contrast to 0/5 patients with BM
involvement. This was confirmed in a multivariate analysis. There was no
correlation between BM involvement and the number of metastases at diagnosis.
CONCLUSION: The MetaEICESS protocols yield long-term disease-free survival in
patients with advanced Ewing sarcoma. Allogeneic stem cell transplantation was
not associated with increased death of complications. Bone marrow involvement is
a risk factor distinct from multiple bone metastases.
PMID- 27486824
TI - Ionofore antibiotic polynactin produced by Streptomyces sp. 156A isolated from
Lake Baikal.
AB - The potential antibacterial activity of secondary metabolites produced by
Streptomyces sp. 156A isolated from Lake Baikal was investigated. The selective
liquid-liquid extraction method was applied to obtain a mixture of nactins
(polynactin) produced by the strain. The polynactin consisted of nonactin (3%),
monactin (18%), dinactin (36%), trinactin (31%) and tetranactin (12%). The
compounds were identified by MS/MS, 1H and 13C NMR methods. The loss of neutral
184 and 198 Da fragments from a sodiated molecular ion, [M + Na]+, of nactins was
observed in the MS/MS spectrum. The polynactin was shown to possess the
antibiotic activity against Gram-positive strains including opportunistic strains
and strains isolated from various ecosystems of Lake Baikal.
PMID- 27486823
TI - The lncRNA MALAT1 is a novel biomarker for gastric cancer metastasis.
AB - The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is frequently
over-expressed and serves as a prognostic marker in human cancers. However,
little is known about the role of MALAT1 in gastric cancer. Here, we reported
that the tissue and plasma MALAT1 levels were significantly higher in gastric
cancer patients with distant metastasis (P<0.01) than patients without distant
metastasis and the healthy controls. In addition, high levels of plasma MALAT1
independently correlated to a poor prognosis for gastric cancer patients (hazard
ratio, 0.242; 95% CI, 0.154-0.836; P=0.036; Cox regression analysis). Functional
studies revealed that knockdown of MALAT1 could inhibit cell proliferation, cell
cycle progression, migration and invasion, and promote apoptosis in gastric
cancer cells. Furthermore, the miR-122-IGF-1R signaling correlated with the
dysregulated MALAT1 expression in gastric cancer. These data suggest that MALAT1
could function as an oncogene in gastric cancer, and high MALAT1 level could
serve as a potential biomarker for the distant metastasis of gastric cancer.
PMID- 27486825
TI - Prevalence of Psychoactive Substance Consumption in People With Obesity.
AB - OBJECTIVE: The aim of this study was to evaluate the prevalence and the kind of
psychoactive substances consumed by people with obesity. METHODS: Patients were
included at their first visit for bariatric surgery. Socio-demographic
characteristics, anxiety, depressive disorders and psychoactive substance
consumption were assessed. The prevalence of psychoactive substance consumption
was compared to that of the general population reported by the French National
Institute of Prevention and Health Education. RESULTS: One hundred (100) patients
were consecutively recruited: 60 women (mean age 41 +/- 14 years) and 40 men
(mean age 46 +/- 13 years). Sixty-seven percent of subjects consumed alcohol.
Consumption rates of cannabis (21% vs. 10%), cocaine (7.0% vs. 0.8%) and
amphetamine (6.0% vs. 0.3%) were significantly (p < .0001) higher in people with
obesity than in the general population. CONCLUSIONS: People with obesity have an
excess risk of amphetamine, cocaine and cannabis consumption. This consumption
may increase the risk of cardiovascular and psychiatric morbidity and should
therefore be detected before surgery.
PMID- 27486826
TI - l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in
Zebrafish Embryo Model.
AB - This work establishes the zebrafish embryo model for ionizing radiation (IR)
modifier research and also evaluates the protective effect of l-alpha
glycerylphosphorylcholine (GPC). Embryos were exposed to a single-fraction whole
body gamma irradiation (5, 10, 15, and 20 Gy) at different postfertilization time
points and were serially assessed for viability and macro- and micromorphologic
abnormalities. After toxicity evaluation, 194 MUM of GPC was added for certain
groups with 3-h incubation before the radiation. Nuclear factor kappa B (NF
kappaB) and interleukin-1beta (IL-1beta) expression changes were measured using
quantitative real-time polymerase chain reaction. A higher sensitivity could be
observed at earlier stages of the embryogenesis. The lethal dose (LD50) for 6
hours postfertilization (hpf) embryos was 15 Gy and for 24 hpf was 20 Gy on day
7, respectively. GPC administration resulted in a significant improvement in both
the distortion rate and survival of the 24 hpf embryos. Qualitative evaluation of
the histological changes confirmed the protective effect of GPC. IL-1beta and NF
kappaB overexpression due to 10 Gy irradiation was also reduced by GPC. GPC
exhibited promising radioprotective effects in our zebrafish embryo model,
decreasing the irradiation-induced morphological damage and lethality with
significant reduction of IR-caused pro-inflammatory activation.
PMID- 27486827
TI - Multitask Imidazolium Salt Additives for Innovative Poly(l-lactide) Biomaterials:
Morphology Control, Candida spp. Biofilm Inhibition, Human Mesenchymal Stem Cell
Biocompatibility, and Skin Tolerance.
AB - Candida species have great ability to colonize and form biofilms on medical
devices, causing infections in human hosts. In this study, poly(l-lactide) films
with different imidazolium salt (1-n-hexadecyl-3-methylimidazolium chloride
(C16MImCl) and 1-n-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS))
contents were prepared, using the solvent casting process. Poly(l-lactide)
imidazolium salt films were obtained with different surface morphologies
(spherical and directional), and the presence of the imidazolium salt in the
surface was confirmed. These films with different concentrations of the
imidazolium salts C16MImCl and C16MImMeS presented antibiofilm activity against
isolates of Candida tropicalis, Candida parapsilosis, and Candida albicans. The
minor antibiofilm concentration assay enabled one to determine that an increasing
imidazolium salt content promoted, in general, an increase in the inhibition
percentage of biofilm formation. Scanning electron microscopy micrographs
confirmed the effective prevention of biofilm formation on the imidazolium salt
containing biomaterials. Lower concentrations of the imidazolium salts showed no
cytotoxicity, and the poly(l-lactide)-imidazolium salt films presented good cell
adhesion and proliferation percentages with human mesenchymal stem cells.
Furthermore, no acute microscopic lesions were identified in the
histopathological evaluation after contact between the films and pig ear skin. In
combination with the good morphological, physicochemical, and mechanical
properties, these poly(l-lactide)-based materials with imidazolium salt additives
can be considered as promising biomaterials for use in the manufacturing of
medical devices.
PMID- 27486828
TI - Experimental and Quantum Chemical Calculations of Imidazolium Appended
Naphthalene Hybrid in Different Biomimicking Aqueous Interfaces.
AB - The effect of solvent polarity and micellar headgroup on a newly designed
imidazolium based ionic liquid (IL) conjugated with naphthalene, 1,2-dimethyl-3
((6-(octyloxy)naphthalen-2-yl)methyl)-1H-imidazol-3-ium chloride (IN-O8-Cl), was
studied using steady state and time-resolved fluorescence techniques. We observed
that the dipole moment in the excited state is remarkably higher than the ground
state. The effect of micellar surface charge on the photophysics of IN-O8-Cl in
aqueous phase at room temperature was investigated. Formation of premicellar
aggregates in sodium dodecylsulfate (SDS) was perceived; further the
microenvironment of IN-O8-Cl was examined using steady-state fluorescence
spectroscopy. Micropolarity of the micellar environment of SDS was found to be
lower than that of cetyltrimethylammonium bromide (CTAB) and triton X-100 (TX100)
following the order SDS < TX-100 < CTAB. The binding constant (Kb) and edge
excitation red shift (EERS) from the emission maximum suggest that the probe
binds strongly to the micelles. Multiexponential behavior was observed in time
resolved fluorescence lifetime studies in all micellar environments. We have
observed an increase in rotational correlation time as we move from pure aqueous
phase to solution containing surfactants of different head charge. Varieties of
spectral parameters were used to justify the region in which the probe is
present. The experimentally obtained dipole moment data were justified and
explained by the DFT calculations of the electronic properties of IN-O8-Cl
molecules in gas phase and in selected solvents.
PMID- 27486829
TI - Mechanism and Selectivity in the Pd-Catalyzed Difunctionalization of Isoprene.
AB - The three-component coupling of isoprene, an alkenyl triflate, and
styrenylboronic acid catalyzed by a palladium pyrox complex affords access to
skipped dienes from simple chemical feedstocks. Unfortunately, the transformation
proceeds with only moderate selectivity and yields. The reaction mechanism and
factors responsible for the resulting regioselectivity were elucidated using
M06/SDD/6-311++G(d,p) + SMD calculations. Distortion of the palladium
coordination sphere in the transition structure of the migratory insertion step
is found to control the 4,1- vs 1,x-selectivity. The calculated DeltaDeltaG? of
1.0 kcal/mol for this step is in excellent agreement with the experimentally
observed selectivity of 1:9.9 disfavoring the 4,1-product. The transmetalation
was found to be the regioselectivity determining step for the formation of the
1,2- vs 1,4-addition products. Systematic conformational searches for the
transmetalation transition structure revealed a series of steric interactions
between the t-Bu substituent on the ligand and the substrates in the model system
that are balanced by additional repulsive interactions between the substrates and
the pyridyl portion of the ligand. The combination of these effects leads to the
low to moderate 1,2- vs 1,4-selectivity in the experimentally studied system.
PMID- 27486830
TI - Ceramide-Induced Lamellar Gel Phases in Fluid Cell Lipid Extracts.
AB - The effects of increasing amounts of palmitoylceramide (pCer) on human red blood
cell lipid membranes have been studied using atomic force microscopy of supported
lipid bilayers, in both imaging (bilayer thickness) and force-spectroscopy
(nanomechanical resistance) modes. Membranes appeared homogeneous with pCer
concentrations up to 10 mol % because of the high concentration of cholesterol
(Chol) present in the membrane (~45 mol %). However, the presence of pCer at 30
mol % gave rise to a clearly distinguishable segregated phase with a
nanomechanical resistance 7-fold higher than the continuous phase. These
experiments were validated using differential scanning calorimetry. Furthermore,
Chol depletion of the bilayers caused lipid domain generation in the originally
homogeneous samples, and Chol-depleted domain stiffness significantly increased
with higher amounts of pCer. These results point to the possibility of different
kinds of transient and noncompositionally constant, complex gel-like phases
present in RBC lipid membranes rich in both pCer and Chol, in contrast to the
widespread opinion about the displacements between pCer-enriched "gel-like"
domains and liquid-ordered "raft-like" Chol-enriched phases. Changes in the
biophysical properties of these complex gel-like phases governed by local
modulation of pCer:Chol ratios could be a cell mechanism for fine-tuning the
properties of membranes as required.
PMID- 27486831
TI - Lewis Acid Catalyzed Displacement of Trichloroacetimidates in the Synthesis of
Functionalized Pyrroloindolines.
AB - The pyrroloindoline core is found in many natural products. These structures
often differ at the C3a position, which may be substituted with an oxygen,
nitrogen, or sp(3)- or sp(2)-hybridized carbon. Utilizing a trichloroacetimidate
leaving group, a diversity-oriented approach to these structures has been
developed. The trichloroacetimidate intermediate allows for the rapid
incorporation of anilines, alcohols, thiols, and carbon nucleophiles. This method
was applied in the synthesis of arundinine and a formal synthesis of
psychotriasine.
PMID- 27486832
TI - Effects of Rate-Limited Mass Transfer on Modeling Vapor Intrusion with Aerobic
Biodegradation.
AB - Most of the models for simulating vapor intrusion accept the local equilibrium
assumption for multiphase concentration distributions, that is, concentrations in
solid, liquid and vapor phases are in equilibrium. For simulating vapor transport
with aerobic biodegradation controlled by counter-diffusion processes, the local
equilibrium assumption combined with dual-Monod kinetics and biomass decay may
yield near-instantaneous behavior at steady state. The present research
investigates how predicted concentration profiles and fluxes change as interphase
mass transfer resistances are increased for vapor intrusion with aerobic
biodegradation. Our modeling results indicate that the attenuation coefficients
for cases with and without mass transfer limitations can be significantly
different by orders of magnitude. Rate-limited mass transfer may lead to larger
overlaps of contaminant vapor and oxygen concentrations, which cannot be
simulated by instantaneous reaction models with local equilibrium mass transfer.
In addition, the contaminant flux with rate-limited mass transfer is much smaller
than that with local equilibrium mass transfer, indicating that local equilibrium
mass transfer assumption may significantly overestimate the biodegradation rate
and capacity for mitigating vapor intrusion through the unsaturated zone. Our
results indicate a strong research need for field tests to examine the validity
of local equilibrium mass transfer, a widely accepted assumption in modeling
vapor intrusion.
PMID- 27486833
TI - Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and
Selective Aldo-keto Reductase 1C3 Inhibitor.
AB - Type 5 17beta-hydroxysteroid dehydrogenase, aldo-keto reductase 1C3 (AKR1C3)
converts Delta(4)-androstene-3,17-dione and 5alpha-androstane-3,17-dione to
testosterone (T) and 5alpha-dihydrotestosterone, respectively, in castration
resistant prostate cancer (CRPC). In CRPC, AKR1C3 is implicated in drug
resistance, and enzalutamide drug resistance can be surmounted by indomethacin a
potent inhibitor of AKR1C3. We examined a series of naproxen analogues and find
that (R)-2-(6-methoxynaphthalen-2-yl)butanoic acid (in which the methyl group of
R-naproxen was replaced by an ethyl group) acts as a potent AKR1C3 inhibitor that
displays selectivity for AKR1C3 over other AKR1C enzymes. This compound was
devoid of inhibitory activity on COX isozymes and blocked AKR1C3 mediated
production of T and induction of PSA in LNCaP-AKR1C3 cells as a model of a CRPC
cell line. R-Profens are substrate selective COX-2 inhibitors and block the
oxygenation of endocannabinoids and in the context of advanced prostate cancer R
profens could inhibit intratumoral androgen synthesis and act as analgesics for
metastatic disease.
PMID- 27486834
TI - Characterization of Key Aroma Compounds in Raw and Thermally Processed Prawns and
Thermally Processed Lobsters by Application of Aroma Extract Dilution Analysis.
AB - Application of aroma extract dilution analysis (AEDA) to an aroma distillate of
blanched prawn meat (Litopenaeus vannamei) (BPM) revealed 40 odorants in the
flavor dilution (FD) factor range from 4 to 1024. The highest FD factors were
assigned to 2-acetyl-1-pyrroline, 3-(methylthio)propanal, (Z)-1,5-octadien-3-one,
trans-4,5-epoxy-(E)-2-decenal, (E)-3-heptenoic acid, and 2-aminoacetophenone. To
understand the influence of different processing conditions on odorant formation,
fried prawn meat was investigated by means of AEDA in the same way, revealing 31
odorants with FD factors between 4 and 2048. Also, the highest FD factors were
determined for 2-acetyl-1-pyrroline, 3-(methylthio)propanal, and (Z)-1,5-octadien
3-one, followed by 4-hydroxy-2,5-dimethyl-3(2H)-furanone, (E)-3-heptenoic acid,
and 2-aminoacetophenone. As a source of the typical marine, sea breeze-like odor
attribute of the seafood, 2,4,6-tribromoanisole was identified in raw prawn meat
as one of the contributors. Additionally, the aroma of blanched prawn meat was
compared to that of blanched Norway and American lobster meat, respectively
(Nephrops norvegicus and Homarus americanus). Identification experiments revealed
the same set of odorants, however, with differing FD factors. In particular, 3
hydroxy-4,5-dimethyl-2(5H)-furanone was found as the key aroma compound in
blanched Norway lobster, whereas American lobster contained 3-methylindole with a
high FD factor.
PMID- 27486835
TI - Xylitol for preventing acute otitis media in children up to 12 years of age.
AB - BACKGROUND: Acute otitis media (AOM) is the most common bacterial infection among
young children in the United States. There are limitations and concerns over its
treatment with antibiotics and surgery and so effective preventative measures are
attractive. A potential preventative measure is xylitol, a natural sugar
substitute that reduces the risk of dental decay. Xylitol can reduce the
adherence of Streptococcus pneumoniae (S pneumoniae) and Haemophilus influenzae
(H influenzae) to nasopharyngeal cells in vitro. This is an update of a review
first published in 2011. OBJECTIVES: To assess the efficacy and safety of xylitol
to prevent AOM in children aged up to 12 years. SEARCH METHODS: We searched
CENTRAL (to Issue 12, 2015), MEDLINE (1950 to January 2016), Embase (1974 to
January 2016), CINAHL (1981 to January 2016), LILACS (1982 to January 2016), Web
of Science (2011 to January 2016) and International Pharmaceutical Abstracts
(2000 to January 2016). SELECTION CRITERIA: Randomised controlled trials (RCTs)
or quasi-RCTs of children aged 12 years or younger where xylitol supplementation
was compared with placebo or no treatment to prevent AOM. DATA COLLECTION AND
ANALYSIS: Two review authors independently selected trials from search results,
assessed and rated study quality and extracted relevant data for inclusion in the
review. We contacted trial authors to request missing data. We noted data on any
adverse events of xylitol. We extracted data on relevant outcomes and estimated
the effect size by calculating risk ratio (RR), risk difference (RD) and
associated 95% confidence intervals (CI). MAIN RESULTS: We identified five
clinical trials that involved 3405 children for inclusion. For this 2016 update,
we identified one new trial for inclusion. This trial was systematically reviewed
but due to several sources of heterogeneity, was not included in the meta
analysis. The remaining four trials were of adequate methodological quality. In
three RCTs that involved a total of 1826 healthy Finnish children attending
daycare, there is moderate quality evidence that xylitol (in any form) can reduce
the risk of AOM from 30% to around 22% compared with the control group (RR 0.75,
95% CI 0.65 to 0.88). Among the reasons for dropouts, there were no significant
differences in abdominal discomfort and rash between the xylitol and the control
groups. Xylitol was not effective in reducing AOM among healthy children during a
respiratory infection (RR 1.13, 95% CI 0.83 to 1.53; moderate quality evidence)
or among otitis-prone healthy children (RR 0.90, 95% CI 0.67 to 1.21; low-quality
evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence showing that
the prophylactic administration of xylitol among healthy children attending
daycare centres can reduce the occurrence of AOM. There is inconclusive evidence
with regard to the efficacy of xylitol in preventing AOM among children with
respiratory infection, or among otitis-prone children. The meta-analysis was
limited because data came from a small number of studies, and most were from the
same research group.
PMID- 27486836
TI - Home telemonitoring and remote feedback between clinic visits for asthma.
AB - BACKGROUND: Asthma is a chronic disease that causes reversible narrowing of the
airways due to bronchoconstriction, inflammation and mucus production. Asthma
continues to be associated with significant avoidable morbidity and mortality.
Self management facilitated by a healthcare professional is important to keep
symptoms controlled and to prevent exacerbations.Telephone and Internet
technologies can now be used by patients to measure lung function and asthma
symptoms at home. Patients can then share this information electronically with
their healthcare provider, who can provide feedback between clinic visits.
Technology can be used in this manner to improve health outcomes and prevent the
need for emergency treatment for people with asthma and other long-term health
conditions. OBJECTIVES: To assess the efficacy and safety of home telemonitoring
with healthcare professional feedback between clinic visits, compared with usual
care. SEARCH METHODS: We identified trials from the Cochrane Airways Review Group
Specialised Register (CAGR) up to May 2016. We also searched
www.clinicaltrials.gov, the World Health Organization (WHO) trials portal and
reference lists of other reviews, and we contacted trial authors to ask for
additional information. SELECTION CRITERIA: We included parallel randomised
controlled trials (RCTs) of adults or children with asthma in which any form of
technology was used to measure and share asthma monitoring data with a healthcare
provider between clinic visits, compared with other monitoring or usual care. We
excluded trials in which technologies were used for monitoring with no input from
a doctor or nurse. We included studies reported as full-text articles, those
published as abstracts only and unpublished data. DATA COLLECTION AND ANALYSIS:
Two review authors screened the search and independently extracted risk of bias
and numerical data, resolving disagreements by consensus.We analysed dichotomous
data as odds ratios (ORs) while using study participants as the unit of analysis,
and continuous data as mean differences (MDs) while using random-effects models.
We rated evidence for all outcomes using the GRADE (Grades of Recommendation,
Assessment, Development and Evaluation Working Group) approach. MAIN RESULTS: We
found 18 studies including 2268 participants: 12 in adults, 5 in children and one
in individuals from both age groups. Studies generally recruited people with mild
to moderate persistent asthma and followed them for between three and 12 months.
People in the intervention group were given one of a variety of technologies to
record and share their symptoms (text messaging, Web systems or phone calls),
compared with a group of people who received usual care or a control
intervention.Evidence from these studies did not show clearly whether asthma
telemonitoring with feedback from a healthcare professional increases or
decreases the odds of exacerbations that require a course of oral steroids (OR
0.93, 95% confidence Interval (CI) 0.60 to 1.44; 466 participants; four studies),
a visit to the emergency department (OR 0.75, 95% CI 0.36 to 1.58; 1018
participants; eight studies) or a stay in hospital (OR 0.56, 95% CI 0.21 to 1.49;
1042 participants; 10 studies) compared with usual care. Our confidence was
limited by imprecision in all three primary outcomes. Evidence quality ratings
ranged from moderate to very low. None of the studies recorded serious or non
serious adverse events separately from asthma exacerbations.Evidence for measures
of asthma control was imprecise and inconsistent, revealing possible benefit over
usual care for quality of life (MD 0.23, 95% CI 0.01 to 0.45; 796 participants;
six studies; I(2) = 54%), but the effect was small and study results varied.
Telemonitoring interventions may provide additional benefit for two measures of
lung function. AUTHORS' CONCLUSIONS: Current evidence does not support the
widespread implementation of telemonitoring with healthcare provider feedback
between asthma clinic visits. Studies have not yet proven that additional
telemonitoring strategies lead to better symptom control or reduced need for oral
steroids over usual asthma care, nor have they ruled out unintended harms.
Investigators noted small benefits for quality of life, but these are subject to
risk of bias, as the studies were unblinded. Similarly, some benefits for lung
function are uncertain owing to possible attrition bias.Larger pragmatic studies
in children and adults could better determine the real-world benefits of these
interventions for preventing exacerbations and avoiding harms; it is difficult to
generalise results from this review because benefits may be explained at least in
part by the increased attention participants receive by taking part in clinical
trials. Qualitative studies could inform future research by focusing on patient
and provider preferences, or by identifying subgroups of patients who are more
likely to attain benefit from closer monitoring, such as those who have frequent
asthma attacks.
PMID- 27486837
TI - Psychosocial Interventions for Adolescents and Young Adults Diagnosed with Cancer
During Adolescence: A Critical Review.
AB - Adolescents and young adults (AYA) face individual and social challenges
different to other age groups that shape their experience of cancer and the
associated psychological distress. This critical review examined the availability
of AYA-specific psychosocial interventions to assess the impact they have and
identify elements that make them successful. Five literature databases were
searched for psychosocial intervention studies involving AYAs with cancer, on and
off treatment, aged 10-30 years, published between 1980 and 2016. Eleven out of
42 identified studies were included in the final review after quality assessment.
All but two interventions showed positive results on at least one measure of
psychosocial well-being. A distinctive difference between the supportive needs of
those on and off treatment was noted, and differences in intervention design and
delivery formats were identified between the two subgroups. Analysis of specific
intervention characteristics that achieved the successful outcomes was more
challenging due to the large variation in outcome measures used. This review
demonstrates that psychosocial intervention research for AYA with cancer is
increasing and the results show a potential benefit of intervention
participation. Further work is needed to validate whether the benefits achieved
by intervention participation remain over time.
PMID- 27486838
TI - Variation in stiffness regulates cardiac myocyte hypertrophy via signaling
pathways.
AB - Much diseased human myocardial tissue is fibrotic and stiff, which increases the
work that the ventricular myocytes must perform to maintain cardiac output. The
hypothesis tested is that the increased load due to greater stiffness of the
substrata drives sarcomere assembly of cells, thus strengthening them. Neonatal
rat ventricular myocytes (NRVM) were cultured on polyacrylamide or
polydimethylsiloxane substrates with stiffness of 10 kPa, 100 kPa, or 400 kPa, or
glass with stiffness of 61.9 GPa. Cell size increased with stiffness. Two
signaling pathways were explored, phosphorylation of focal adhesion kinase (p
FAK) and lipids by phosphatidylinositol 4,5-bisphosphate (PIP2). Subcellular
distributions of both were determined in the sarcomeric fraction by antibody
localization, and total amounts were measured by Western or dot blotting,
respectively. More p-FAK and PIP2 distributed to the sarcomeres of NRVM grown on
stiffer substrates. Actin assembly involves the actin capping protein Z (CapZ).
Both actin and CapZ dynamic exchange were significantly increased on stiffer
substrates when assessed by fluorescence recovery after photobleaching (FRAP) of
green fluorescent protein tags. Blunting of actin FRAP by FAK inhibition
implicates linkage from mechano-signalling pathways to cell growth. Thus,
increased stiffness of cardiac disease can be modeled with polymeric materials to
understand how the microenvironment regulates cardiac hypertrophy.
PMID- 27486840
TI - Correction to: Thyroid 2016;26:189-196.
PMID- 27486841
TI - Thiocyanate-Ligated Heterobimetallic {PtM} Lantern Complexes Including a
Ferromagnetically Coupled 1D Coordination Polymer.
AB - A series of heterobimetallic lantern complexes with the central unit
{PtM(SAc)4(NCS)} have been prepared and thoroughly characterized. The
{Na(15C5)}[PtM(SAc)4(NCS)] series, 1 (Co), 2 (Ni), 3 (Zn), are discrete compounds
in the solid state, whereas the {Na(12C4)2)}[PtM(SAc)4(NCS)] series, 4 (Co), 5
(Ni), 6 (Zn), and 7 (Mn), are ion-separated species. Compound 7 is the first
{PtMn} lantern of any bridging ligand (carboxylate, amide, etc.). Monomeric 1-7
have M(2+), necessitating counter cations that have been prepared as
{(15C5)Na}(+) and {(12C4)2Na}(+) variants, none of which form extended
structures. In contrast, neutral [PtCr(tba)4(NCS)]infinity 8 forms a coordination
polymer of {PtCr}(+) units linked by (NCS)(-) in a zigzag chain. All eight
compounds have been thoroughly characterized and analyzed in comparison to a
previously reported family of compounds. Crystal structures are presented for
compounds 1-6 and 8, and solution magnetic susceptibility measurements are
presented for compounds 1, 2, 4, 5, and 7. Further structural analysis of
dimerized {PtM} units reinforces the empirical observation that greater charge
density along the Pt-M vector leads to more Pt...Pt interactions in the solid
state. Four structural classes, one new, of {MPt}...{PtM} units are presented.
Solid state magnetic characterization of 8 reveals a ferromagnetic interaction in
the {PtCr(NCS)} chain between the Cr centers of J/kB = 1.7(4) K.
PMID- 27486842
TI - Passivation of hematite nanorod photoanodes with a phosphorus overlayer for
enhanced photoelectrochemical water oxidation.
AB - Hematite (i.e., alpha-Fe2O3) nanorod photoanodes passivated with a phosphorus
overlayer have been fabricated by decomposing sodium hypophosphite (NaH2PO2) at a
low temperature over the hematite nanorod surface. Extensive scanning electron
microscopy, transmission electron microscopy, x-ray diffractometry and UV-vis
spectroscopy characterizations confirm that conformal deposition of an amorphous
phosphorus overlayer does not change the crystal structure, morphology, and
optical absorption properties of hematite photoanodes. X-ray photoelectron
spectroscopy reveals that phosphorus in the deposited overlayer exists in an
oxidized state. Comprehensive steady-state polarization, transient photocurrent
response, and impedance spectroscopy measurements as well as Mott-Schottky
analysis manifest that the phosphorus overlayer is able to effectively passivate
surface states and suppress electron-hole recombination, substantially enhancing
the photocurrent for water oxidation. Combining the phosphorization treatment
with two-step thermal activation, a photocurrent density of 1.1 mA cm(-2) is
achieved at 1.23 V versus reversible hydrogen electrode under illumination of 100
mW cm(-2), ca 55 times higher than that of the non-activated pristine hematite
photoanode measured under the same conditions. The simple and fast
phosphorization strategy we present here can be readily applied to passivate
surfaces of other semiconductor photoelectrodes to improve their
photoelectrochemical performance.
PMID- 27486843
TI - Pain Intensity and Pain Interference in Older Adults: Role of Gender, Obesity and
High-Sensitivity C-Reactive Protein.
AB - BACKGROUND: Among older adults, pain intensity and pain interference are more
common in women than men and associated with obesity and inflammatory markers.
OBJECTIVE: We examined whether the obesity and pain relationship is mediated by
the high-sensitivity C-reactive protein (hsCRP), a nonspecific marker of systemic
inflammation, and whether this relationship differs by sex. METHODS: Items from
Medical Outcomes Study Short Form-36 were used to measure pain intensity and pain
interference in daily life. Ordinal logistic regression was used to assess the
cross-sectional association among body mass index (BMI), hsCRP levels, pain
intensity and pain interference using gender-stratified models adjusted for
demographic variables. RESULTS: Participants included 667 community-residing
adults over the age of 70 years, free of dementia, enrolled in the Einstein Aging
Study (EAS). In women (n = 410), pain intensity was associated with obesity [BMI
>=30 vs. normal, odds ratio (OR) = 2.29, 95% confidence interval (CI) 1.43-3.68]
and higher hsCRP (OR = 1.28, 95% CI 1.08-1.51). In a model with obesity and
hsCRP, both remained significant, but the association between hsCRP and pain
intensity was somewhat attenuated. Obesity (OR = 3.04, 95% CI 1.81-5.11) and
higher hsCRP levels (OR = 1.30, 95% CI 1.08-1.56) were also independently
associated with greater pain interference in women. After adjustment for pain
intensity and BMI, hsCRP was no longer associated with pain interference in
women. Greater pain intensity and being overweight or obese continued to be
significantly associated with pain interference in women. In men (n = 257),
obesity and hsCRP were not associated with pain intensity or pain interference.
CONCLUSIONS: In women, the relationship between obesity and higher levels of pain
intensity or interference may be accounted for by factors related to hsCRP.
PMID- 27486844
TI - A Novel Role for Banana MaASR in the Regulation of Flowering Time in Transgenic
Arabidopsis.
AB - The abscisic acid (ABA)-, stress-, and ripening-induced (ASR) protein is a plant
specific hydrophilic transcriptional factor involved in fruit ripening and the
abiotic stress response. To date, there have been no studies on the role of ASR
genes in delayed flowering time. Here, we found that the ASR from banana,
designated as MaASR, was preferentially expressed in the banana female flowers
from the eighth, fourth, and first cluster of the inflorescence. MaASR transgenic
lines (L14 and L38) had a clear delayed-flowering phenotype. The number of
rosette leaves, sepals, and pedicel trichomes in L14 and L38 was greater than in
the wild type (WT) under long day (LD) conditions. The period of buds, mid
flowers, and full bloom of L14 and L38 appeared later than the WT. cDNA
microarray and quantitative real-time PCR (qRT-PCR) analyses revealed that
overexpression of MaASR delays flowering through reduced expression of several
genes, including photoperiod pathway genes, vernalization pathway genes,
gibberellic acid pathway genes, and floral integrator genes, under short days
(SD) for 28 d (from vegetative to reproductive transition stage); however, the
expression of the autonomous pathway genes was not affected. This study provides
the first evidence of a role for ASR genes in delayed flowering time in plants.
PMID- 27486845
TI - Relocating the Active-Site Lysine in Rhodopsin: 2. Evolutionary Intermediates.
AB - The visual pigment rhodopsin is a G protein-coupled receptor that covalently
binds its retinal chromophore via a Schiff base linkage to an active-site Lys
residue in the seventh transmembrane helix. Although this residue is strictly
conserved among all type II retinylidene proteins, we found previously that the
active-site Lys in bovine rhodopsin (Lys296) can be moved to three other
locations (G90K, T94K, S186K) while retaining the ability to form a pigment with
retinal and to activate transducin in a light-dependent manner [ Devine et al. (
2013 ) Proc. Natl. Acad. Sci. USA 110 , 13351 - 13355 ]. Because the active-site
Lys is not functionally constrained to be in helix seven, it is possible that it
could relocate within the protein, most likely via an evolutionary intermediate
with two active-site Lys. Therefore, in this study we characterized potential
evolutionary intermediates with two Lys in the active site. Four mutant
rhodopsins were prepared in which the original Lys296 was left untouched and a
second Lys residue was substituted for G90K, T94K, S186K, or F293K. All four
constructs covalently bind 11-cis-retinal, form a pigment, and activate
transducin in a light-dependent manner. These results demonstrate that rhodopsin
can tolerate a second Lys in the retinal binding pocket and suggest that an
evolutionary intermediate with two Lys could allow migration of the Schiff base
Lys to a position other than the observed, highly conserved location in the
seventh TM helix. From sequence-based searches, we identified two groups of
natural opsins, insect UV cones and neuropsins, that contain Lys residues at two
positions in their active sites and also have intriguing spectral similarities to
the mutant rhodopsins studied here.
PMID- 27486846
TI - Seeing for themselves - healthcare professionals' views about the presence of
family members during brainstem death testing.
AB - AIMS AND OBJECTIVES: To provide an insight into the views of healthcare
professionals on the presence of family members during brainstem death testing.
BACKGROUND: Brainstem death presents families with a paradoxical death that can
be difficult to define. International research suggests families should be given
the choice to be present at brainstem death testing, yet it appears few units
offer families the choice to be present and little attention has been paid to
developing practice to enable effective facilitation of choice. DESIGN: A
qualitative, exploratory design was adopted to understand the perceptions of
healthcare professionals. Individual semi-structured interviews were audio-taped
and carried out over two months. METHODS: A purposive sample of 10 nurses and 10
doctors from two tertiary intensive care units in the United Kingdom was
interviewed, and transcripts were analysed using content analysis to identify
emergent categories and themes. RESULTS: Healthcare professionals indicated
different perceptions of death in the context of catastrophic brainstem injury.
The majority of participants favoured offering families the choice to be present
while acknowledging the influence of organisational culture. Identified benefits
included acceptance, closure and better understanding. Suggested challenges
involved the assumption of trauma or disruption and sense of obligation for
families to accept if choice was offered. Key issues involved improving knowledge
and communication skills to individually tailor support for families involved.
CONCLUSIONS: If families are to be offered the choice of witnessing brainstem
death testing, considering that needs and conventions will differ according to
global cultural backgrounds, then key needs must be met to ensure that effective
care and support is provided to families and clinicians. RELEVANCE TO CLINICAL
PRACTICE: A proactive approach to facilitating family choice to be present at
testing requires the development of guidelines that accommodate cultural and
professional variations to provide excellence in end-of-life care.
PMID- 27486847
TI - The Role of Temporal Trends in Growing Networks.
AB - The rich get richer principle, manifested by the Preferential attachment (PA)
mechanism, is widely considered one of the major factors in the growth of real
world networks. PA stipulates that popular nodes are bound to be more attractive
than less popular nodes; for example, highly cited papers are more likely to
garner further citations. However, it overlooks the transient nature of
popularity, which is often governed by trends. Here, we show that in a wide range
of real-world networks the recent popularity of a node, i.e., the extent by which
it accumulated links recently, significantly influences its attractiveness and
ability to accumulate further links. We proceed to model this observation with a
natural extension to PA, named Trending Preferential Attachment (TPA), in which
edges become less influential as they age. TPA quantitatively parametrizes a
fundamental network property, namely the network's tendency to trends. Through
TPA, we find that real-world networks tend to be moderately to highly trendy.
Networks are characterized by different susceptibilities to trends, which
determine their structure to a large extent. Trendy networks display complex
structural traits, such as modular community structure and degree-assortativity,
occurring regularly in real-world networks. In summary, this work addresses an
inherent trait of complex networks, which greatly affects their growth and
structure, and develops a unified model to address its interaction with
preferential attachment.
PMID- 27486848
TI - Emerging biological therapies for the treatment of myelodysplastic syndromes.
AB - INTRODUCTION: No drug has resulted in a survival advantage in patients with lower
risk myelodysplastic syndromes (MDS). While hypomethylating agents (HMA) have
revolutionized treatment options for patients with higher-risk MDS, the prognosis
remains dismal after HMA treatment failure. Novel effective therapies are
urgently needed especially after HMA failure. AREAS COVERED: This review covers
the current approach to disease prognostication and risk-adaptive therapy, as
well as novel therapeutic approaches. We discuss the recent advancements in the
understanding of MDS disease biology as a basis of targeted drug development.
Several classes of novel agents are reviewed including drugs targeting
dysregulated epigenetic control mechanisms, signaling pathways, abnormal
splicing, as well as agents that target the immune system and the MDS bone marrow
niche. EXPERT OPINION: Significant advancements in the understanding of the
underlying biology of MDS are only starting to be translated into novel treatment
options for MDS. Epigenetic therapy has shown significant clinical activity with
HMA but the results of clinical trials combining HMAs with histone deacetylase
inhibitors (HDACi) have been disappointing to date. Similarly, targeting several
aberrant pathways in MDS has not resulted in significant improvements in therapy.
Future therapies will focus both on synergic combination of existing drugs as
well as novel agents targeting dysregulated immune responses and abnormal RNA
splicing in MDS.
PMID- 27486849
TI - Design of cyclic peptides with biological activities from biologically active
peptides: the case of peptide modulators of melanocortin receptors.
AB - Design of biologically active peptides is of critical importance for the
development of potent, selective, nontoxic bioavailable drugs. A major approach
that has been developed to accomplish this is the development of methods for the
design and synthesis of a wide variety of cyclic peptides and peptidomimetics. In
this short and general review, we outline the methods that have been developed
for cyclization of peptides and how these have been used for peptide and
peptidomimetic design using the melanotropin peptides and melanocortin receptors
MC1R, MC3R, MC4R, and MC5R to illustrate aspects of this approach.
PMID- 27486850
TI - Effects of infant massage on state anxiety in mothers of preterm infants prior to
hospital discharge.
AB - AIMS AND OBJECTIVES: This study evaluated the effect of infant massage on anxiety
in mothers of preterm infants who discharged from the neonatal intensive care
unit. BACKGROUND: Birth of preterm infants commonly leads to great levels of
distress and anxiety in mothers. Although various methods have been suggested to
help mothers cope with such stressful conditions, the effects of infant massage
have not been adequately studied in mothers. DESIGN: This was a quasi
experimental clinical trial. METHODS: Overall, in 70 mothers and their preterm
infants who scheduled to be discharged within 24 hours, State-Trait Anxiety
Inventory scale (Spielberger) was completed for mothers in both groups in the
morning of the day before discharge. The experimental group received eight
minutes of massage including two standard similar parts (each part four minutes).
The massage was repeated in two parts on the day of discharge, and then, state
anxiety was re-measured using Spielberg's scale for all mothers. The control
group received no intervention. RESULTS: The results showed that on the day of
discharge, there was a significant difference in the overall mean score of
maternal state anxiety between the two groups (p < 0.002), although not in the
severity of maternal state anxiety. In both groups, the mean score of maternal
state anxiety was significantly decreased on the day of discharge (p < 0.001).
CONCLUSIONS: The findings provide evidence that infant massage by mother has an
effect on the state anxiety of mothers of preterm infants, so it is recommended
that mothers apply massage for preterm infants to improve their mental health.
RELEVANCE TO CLINICAL PRACTICE: Mothers of preterm infants can promote mental
health by continuing massage of their infants at home.
PMID- 27486851
TI - Recommendations of Common Data Elements to Advance the Science of Self-Management
of Chronic Conditions.
AB - PURPOSE: Common data elements (CDEs) are increasingly being used by researchers
to promote data sharing across studies. The purposes of this article are to (a)
describe the theoretical, conceptual, and definition issues in the development of
a set of CDEs for research addressing self-management of chronic conditions; (b)
propose an initial set of CDEs and their measures to advance the science of self
management; and (c) recommend implications for future research and dissemination.
DESIGN AND METHODS: Between July 2014 and December 2015 the directors of the
National Institute of Nursing Research (NINR)-funded P20 and P30 centers of
excellence and NINR staff met in a series of telephone calls and a face-to-face
NINR-sponsored meeting to select a set of recommended CDEs to be used in self
management research. A list of potential CDEs was developed from examination of
common constructs in current self-management frameworks, as well as
identification of variables frequently used in studies conducted in the centers
of excellence. FINDINGS: The recommended CDEs include measures of three self
management processes: activation, self-regulation, and self-efficacy for managing
chronic conditions, and one measure of a self-management outcome, global health.
CONCLUSIONS: The self-management of chronic conditions, which encompasses a
considerable number of processes, behaviors, and outcomes across a broad range of
chronic conditions, presents several challenges in the identification of a
parsimonious set of CDEs. This initial list of recommended CDEs for use in self
management research is provisional in that it is expected that over time it will
be refined. Comment and recommended revisions are sought from the research and
practice communities. CLINICAL RELEVANCE: The use of CDEs can facilitate
generalizability of research findings across diverse population and
interventions.
PMID- 27486852
TI - Tiron Inhibits UVB-Induced AP-1 Binding Sites Transcriptional Activation on MMP-1
and MMP-3 Promoters by MAPK Signaling Pathway in Human Dermal Fibroblasts.
AB - Recent research found that Tiron was an effective antioxidant that could act as
the intracellular reactive oxygen species (ROS) scavenger or alleviate the acute
toxic metal overload in vivo. In this study, we investigated the inhibitory
effect of Tiron on matrix metalloproteinase (MMP)-1 and MMP-3 expression in human
dermal fibroblast cells. Western blot and ELISA analysis revealed that Tiron
inhibited ultraviolet B (UVB)-induced protein expression of MMP-1 and MMP-3. Real
time quantitative PCR confirmed that Tiron could inhibit UVB-induced mRNA
expression of MMP-1 and MMP-3. Furthermore, Tiron significantly blocked UVB
induced activation of the MAPK signaling pathway and activator protein (AP)-1 in
the downstream of this transduction pathway in fibroblasts. Through the AP-1
binding site mutation, it was found that Tiron could inhibit AP-1-induced
upregulation of MMP-1 and MMP-3 expression through blocking AP-1 binding to the
AP-1 binding sites in the MMP-1 and MMP-3 promoter region. In conclusion, Tiron
may be a novel antioxidant for preventing and treating skin photoaging UV
induced.
PMID- 27486853
TI - Oncolytic virus therapy: A new era of cancer treatment at dawn.
AB - Oncolytic virus therapy is perhaps the next major breakthrough in cancer
treatment following the success in immunotherapy using immune checkpoint
inhibitors. Oncolytic viruses are defined as genetically engineered or naturally
occurring viruses that selectively replicate in and kill cancer cells without
harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation
oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently
approved as the first oncolytic virus drug in the USA and Europe. The phase III
trial proved that local intralesional injections with T-Vec in advanced malignant
melanoma patients can not only suppress the growth of injected tumors but also
act systemically and prolong overall survival. Other oncolytic viruses that are
closing in on drug approval in North America and Europe include vaccinia virus JX
594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM-CSF-expressing
adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild-type
variant of reovirus, for head and neck cancer. In Japan, a phase II clinical
trial of G47?, a third-generation oncolytic HSV-1, is ongoing in glioblastoma
patients. G47? was recently designated as a "Sakigake" breakthrough therapy drug
in Japan. This new system by the Japanese government should provide G47? with
priority reviews and a fast-track drug approval by the regulatory authorities.
Whereas numerous oncolytic viruses have been subjected to clinical trials, the
common feature that is expected to play a major role in prolonging the survival
of cancer patients is an induction of specific antitumor immunity in the course
of tumor-specific viral replication. It appears that it will not be long before
oncolytic virus therapy becomes a standard therapeutic option for all cancer
patients.
PMID- 27486854
TI - Mutation in the S gene a determinant of the hepatitis B virus associated with
concomitant HBsAg and anti-HBs in a population in Northeastern Brazil.
AB - Mutations in the a determinant of S gene may develop co-existence of hepatitis B
surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) in the serum of
infected hepatitis B virus (HBV) individuals. Mutations in this region may change
the antigenicity of HBsAg, which in turn, lead to escape of neutralizing action
of anti-HBs antibodies. This study identified individuals with concomitant HBsAg
and anti-HBs serological markers in individuals of Maranhao, Northeastern Brazil.
Samples from a population-based study were evaluated for HBsAg, anti-HBs, and
anti-HBc, and those that tested positive for simultaneous HBsAg and anti-HBs were
submitted to HBV DNA quantification and S gene characterization by Sanger
sequencing. Mutations were investigated in the a determinant located in major
hydrophilic region (MHR) of the S gene. Among 3,984 samples analyzed, 92 (2.3%)
were positive for HBsAg and three had the atypical HBsAg and anti-HBs-positive
profile (3.26%). The frequency of HBsAg and anti-HBs co-existence was similar to
previous studies. Only one individual harbored mutation in the S gene a
determinant associated with this profile. Little is known about this phenomenon;
however, studies as ours may contribute for future enlightenment of this
important issue. J. Med. Virol. 89:458-462, 2017. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27486855
TI - Nutrient Starvation Sensitizes Human Ovarian Cancer SKOV3 Cells to BH3 Mimetic
via Modulation of Mitochondrial Dynamics.
AB - The aberrant proliferation of tumor cells necessitates compensatory changes in
tumor metabolic processes. Previous studies on tumor growth and metabolism have
established a relationship between nutrient stress and Bcl-2 anti-apoptotic
proteins, although the mechanisms connecting these processes remain unclear. We
induced nutrient deprivation in human ovarian cancer SKOV3 cells by culturing
cells in Earle's balanced salt solution (EBSS) as a starvation model. We used
EBSS treatment with the BH3 domain of Bcl-2 family proteins (BH3) mimetic ABT737,
which targets Bcl-2/Bcl-xL, to examine mitochondrial dynamics and the interactive
regulatory mechanisms between nutrition and Bcl-2 proteins. We found that EBSS
combined with ABT737 can promote SKOV3 cells to undergo apoptosis and convert
tubular mitochondria into small, fragmented morphologies. Bcl-2 family proteins
participated in the regulation of mitochondrial fusion and fission through
apoptosis, and the decrease of Mcl-1 expression was the key to ABT737
sensitization. Our findings showed that nutrient stress could sensitize SKOV3
cells to ABT737 via regulation of the mitochondrial dynamic balance and
interaction of Bcl-2 family proteins. Our data suggest that nutrient starvation
combined with the BH3 mimetic ABT737 could reduce the required effective dose of
ABT737, and that inhibition of Bcl-2 and Mcl-1 together with nutrient starvation
could serve as an effective strategy for the treatment of human ovarian cancer.
Anat Rec, 300:326-339, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27486856
TI - Differential Expression of Complement Markers in Normal and AMD
Transmitochondrial Cybrids.
AB - PURPOSE: Variations in mitochondrial DNA (mtDNA) and abnormalities in the
complement pathways have been implicated in the pathogenesis of age-related
macular degeneration (AMD). This study was designed to determine the effects of
mtDNA from AMD subjects on the complement pathway. METHODS: Transmitochondrial
cybrids were prepared by fusing platelets from AMD and age-matched Normal
subjects with Rho0 (lacking mtDNA) human ARPE-19 cells. Quantitative PCR and
Western blotting were performed to examine gene and protein expression profiles,
respectively, of complement markers in these cybrids. Bioenergetic profiles of
Normal and AMD cybrids were examined using the Seahorse XF24 flux analyzer.
RESULTS: Significant decreases in the gene and protein expression of complement
inhibitors, along with significantly higher levels of complement activators, were
found in AMD cybrids compared to Older-Normal cybrids. Seahorse flux data
demonstrated that the bioenergetic profiles for Older-Normal and Older-AMD cybrid
samples were similar to each other but were lower compared to Young-Normal cybrid
samples. CONCLUSION: In summary, since all cybrids had identical nuclei and
differed only in mtDNA content, the observed changes in components of complement
pathways can be attributed to mtDNA variations in the AMD subjects, suggesting
that mitochondrial genome and retrograde signaling play critical roles in this
disease. Furthermore, the similar bioenergetic profiles of AMD and Older-Normal
cybrids indicate that the signaling between mitochondria and nuclei are probably
not via a respiratory pathway.
PMID- 27486857
TI - Informing Investment to Reduce Inequalities: A Modelling Approach.
AB - BACKGROUND: Reducing health inequalities is an important policy objective but
there is limited quantitative information about the impact of specific
interventions. OBJECTIVES: To provide estimates of the impact of a range of
interventions on health and health inequalities. MATERIALS AND METHODS:
Literature reviews were conducted to identify the best evidence linking
interventions to mortality and hospital admissions. We examined interventions
across the determinants of health: a 'living wage'; changes to benefits, taxation
and employment; active travel; tobacco taxation; smoking cessation, alcohol brief
interventions, and weight management services. A model was developed to estimate
mortality and years of life lost (YLL) in intervention and comparison populations
over a 20-year time period following interventions delivered only in the first
year. We estimated changes in inequalities using the relative index of inequality
(RII). RESULTS: Introduction of a 'living wage' generated the largest beneficial
health impact, with modest reductions in health inequalities. Benefits increases
had modest positive impacts on health and health inequalities. Income tax
increases had negative impacts on population health but reduced inequalities,
while council tax increases worsened both health and health inequalities. Active
travel increases had minimally positive effects on population health but widened
health inequalities. Increases in employment reduced inequalities only when
targeted to the most deprived groups. Tobacco taxation had modestly positive
impacts on health but little impact on health inequalities. Alcohol brief
interventions had modestly positive impacts on health and health inequalities
only when strongly socially targeted, while smoking cessation and weight
reduction programmes had minimal impacts on health and health inequalities even
when socially targeted. CONCLUSIONS: Interventions have markedly different
effects on mortality, hospitalisations and inequalities. The most effective (and
likely cost-effective) interventions for reducing inequalities were regulatory
and tax options. Interventions focused on individual agency were much less likely
to impact on inequalities, even when targeted at the most deprived communities.
PMID- 27486858
TI - Infant Respiratory Outcomes Associated with Prenatal Exposure to Maternal 2009
A/H1N1 Influenza Vaccination.
AB - BACKGROUND: Infants are at high risk for influenza illness, but are ineligible
for vaccination before 6 months. Transfer of maternal antibodies to the fetus has
been demonstrated for 2009 A/H1N1 pandemic vaccines; however, clinical
effectiveness is unknown. Our objective was to evaluate the association between
2009 A/H1N1 pandemic vaccination during pregnancy and rates of infant influenza
and pneumonia. METHODS: We linked a population-based birth cohort to
administrative databases to measure rates of influenza and pneumonia diagnosed
during ambulatory physician visits, hospitalizations and emergency department
visits during one year of follow-up. We estimated incidence rate ratios and 95%
confidence intervals (95% CI) using Poisson regression, comparing infants born to
A/H1N1-vaccinated women (vaccine-exposed infants) with unexposed infants,
adjusted for confounding using high-dimensional propensity scores. RESULTS: Among
117,335 infants in the study, 36,033 (31%) were born to A/H1N1-vaccinated women.
Crude rates of influenza during the pandemic (per 100,000 infant-days) for
vaccine-exposed and unexposed infants were similar (2.19, 95% CI: 1.27-3.76 and
3.60, 95% CI: 2.51-5.14, respectively), as were crude rates of influenza and
pneumonia combined. We did not observe any significant differences in rates of
study outcomes between study groups during the second wave of the 2009 A/H1N1
pandemic, nor during any post-pandemic time period. CONCLUSION: We observed no
difference in rates of study outcomes among infants born to A/H1N1-vaccinated
mothers relative to unexposed infants born during the second A/H1N1 pandemic
wave; however, due to late availability of the pandemic vaccine, the available
follow-up time during the pandemic time period was very limited.
PMID- 27486859
TI - Structure and biochemical properties of recombinant human dimethylglycine
dehydrogenase and comparison to the disease-related H109R variant.
AB - : The human dimethylglycine dehydrogenase (hDMGDH) is a flavin adenine
dinucleotide (FAD)- and tetrahydrofolate (THF)-dependent, mitochondrial matrix
enzyme taking part in choline degradation, one-carbon metabolism and electron
transfer to the respiratory chain. The rare natural variant H109R causes
dimethylglycine dehydrogenase deficiency leading to increased blood and urinary
dimethylglycine concentrations. A detailed biochemical and structural
characterization of hDMGDH was thus far hampered by insufficient heterologous
expression of the protein. In the present study, we report the development of an
intracellular, heterologous expression system in Komagataella phaffii (formerly
known as Pichia pastoris) providing the opportunity to determine kinetic
parameters, spectroscopic properties, thermostability, and the redox potential of
hDMGDH. Moreover, we have successfully crystallized the wild-type enzyme and
determined the structure to 3.1-A resolution. The structure-based analysis of our
biochemical data provided new insights into the kinetic properties of the enzyme
in particular with respect to oxygen reactivity. A comparative study with the
H109R variant demonstrated that the variant suffers from decreased protein
stability, cofactor saturation, and substrate affinity. DATABASE: Structural data
are available in the PDB database under the accession number 5L46.
PMID- 27486860
TI - Retrospective characterisation of solitary cutaneous histiocytoma with lymph node
metastasis in eight dogs.
AB - OBJECTIVES: To describe a small subset of canine solitary cutaneous histiocytoma
in which lymph node metastasis has been documented. METHODS: Cases of dogs with
solitary cutaneous histiocytoma lesions and regional lymph node metastasis
diagnosed via histopathology were found through a retrospective search of the
databases of IDEXX Laboratories and the University of California, Davis
Veterinary Medical Teaching Hospital Clinical Diagnostic Laboratories.
Information on signalment, history and clinical follow-up was obtained from the
submittal form and/or via a questionnaire to the submitting veterinarian. Slides
were available for review in seven cases and when possible immunohistochemistry
was reviewed or performed by a single pathologist. RESULTS: Eight cases met the
inclusion criteria. The neoplasms had the typical appearance of histiocytomas.
All tested samples were immunoreactive for CD18 and lacked immunoreactivity for
other lymphocyte markers and CD11d. Immunoreactivity for E-cadherin varied among
the neoplasms tested. Outcome was known for five dogs and at the time of
manuscript preparation three of those dogs were alive 1682 days, 570 days and 318
days post-diagnosis. Of the other two dogs with known outcome, one was euthanased
shortly after diagnosis and another was hit by a car. Of the dogs that were
eventually lost to follow-up, one was reported to be disease-free 1003 days after
diagnosis. CLINICAL SIGNIFICANCE: Metastatic histiocytoma is rarely reported and
distinction from aggressive disease processes such as histiocytic sarcoma may be
difficult. Based upon a small number of cases with known outcomes, some dogs with
solitary metastatic histiocytoma may experience favourable outcomes.
PMID- 27486862
TI - Husbandry and enclosure influences on penguin behavior and conservation breeding.
AB - Multi-zoo comparisons of animal welfare are rare, and yet vital for ensuring
continued improvement of zoo enclosures and husbandry. Methods are not
standardized for the development of zoo enclosures based on multiple indicators,
and case study species are required. This study compares behavior and breeding
success to various enclosure and husbandry parameters for the Humboldt penguin,
Spheniscus humboldti, for the development of improved enclosure design.
Behavioral sampling was completed at Flamingo Land over a period of 8 months.
Further data on behavior, enclosure design, and breeding success were collected
via questionnaires, visits to zoos, and literature review. Breeding success was
primarily influenced by colony age and number of breeding pairs, suggesting an
important social influence on reproduction. Across zoos, there was also
significant variation in behavior. The proportion of time spent in water varied
between zoos (2-23%) and was used as an indicator of physical activity and
natural behavior. Regression models revealed that water-use was best predicted by
total enclosure area per penguin, followed by land area, with some evidence for
positive influence of pool surface area per penguin. Predominantly
linear/curvilinear increases in our biological indicators with enclosure
parameters suggest that optimal conditions for S. humboldti were not met among
the selected zoos. We propose revised minimum conditions for S. humboldti
enclosure design, which exceed those in the existing husbandry guidelines. We
present a framework for the evaluation of zoo enclosures and suggest that a
rigorous scientific protocol be established for the design of new enclosures,
based on multivariate methods. Zoo Biol. 35:385-397, 2016. (c) Wiley Periodicals,
Inc.
PMID- 27486861
TI - LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma.
AB - l-type amino acid transporters (LAT1-4) are expressed in various cancer types and
are involved in the uptake of essential amino acids such as leucine. Here we
investigated the expression of LAT1-4 in endometrial adenocarcinoma and evaluated
the contribution of LATs to endometrial cancer cell growth. Analysis of human
gene expression data showed that all four LAT family members are expressed in
endometrial adenocarcinomas. LAT1 was the most highly expressed, and showed a
significant increase in both serous and endometrioid subtypes compared to normal
endometrium. Endometrioid patients with the highest LAT1 levels exhibited the
lowest disease-free survival. The pan-LAT inhibitor BCH led to a significant
decrease in cell growth and spheroid area in four endometrial cancer cell lines
tested in vitro. Knockdown of LAT1 by shRNA inhibited cell growth in HEC1A and
Ishikawa cells, as well as inhibiting spheroid area in HEC1A cells. These data
show that LAT1 plays an important role in regulating the uptake of essential
amino acids such as leucine into endometrial cancer cells. Increased ability of
BCH compared to LAT1 shRNA at inhibiting Ishikawa spheroid area suggests that
other LAT family members may also contribute to cell growth. LAT1 inhibition may
offer an effective therapeutic strategy in endometrial cancer patients whose
tumours exhibit high LAT1 expression.
PMID- 27486863
TI - The Phenotypic Effects of Royal Jelly on Wild-Type D. melanogaster Are Strain
Specific.
AB - The role for royal jelly (RJ) in promoting caste differentiation of honeybee
larvae into queens rather than workers is well characterized. A recent study
demonstrated that this poorly understood complex nutrition drives strikingly
similar phenotypic effects in Drosophila melanogaster, such as increased body
size and reduced developmental time, making possible the use of D. melanogaster
as a model system for the genetic analysis of the cellular mechanisms underlying
RJ and caste differentiation. We demonstrate here that RJ increases the body size
of some wild-type strains of D. melanogaster but not others, and report
significant delays in developmental time in all flies reared on RJ. These
findings suggest that cryptic genetic variation may be a factor in the D.
melanogaster response to RJ, and should be considered when attempting to
elucidate response mechanisms to environmental changes in non-honeybee species.
PMID- 27486864
TI - Bone marrow stem cells and their niche components are adversely affected in
advanced cirrhosis of the liver.
AB - Bone marrow (BM) is a reservoir for immune and hematopoietic cells and critical
for tissue repair and regeneration. All of these functions are severely altered
in cirrhosis. We investigated the cellular and functional state of BM in
cirrhosis patients. We studied the histological, cellular, and molecular changes
in BM of cirrhosis patients (n = 168) and controls (n = 44). Hematopoietic stem
cells (HSCs) and associated niche cells, mesenchymal stem cells, Schwann cells,
neural fibers, and endothelial cells were evaluated by immunohistochemistry.
Cytokines and growth factors were analyzed in peripheral blood and BM plasma.
Cirrhotic BM showed an inverse correlation between cluster of differentiation
34+HSCs and Model of End-Stage Liver Disease (rho = -0.582, P < 0.001) and
Child's scores (P < 0.038). BMs of cirrhosis patients with higher Model of End
Stage Liver Disease (>15) showed significantly decreased HSCs, mesenchymal stem
cells, Schwann cells, and neural fibers; increased interleukin-1beta (P = 0.004),
tumor necrosis factor-alpha (P = 0.040), and interferon-gamma (P = 0.03); and
decreased oncostatin M (P = 0.04), stem cell factor (P = 0.05), and stromal cell
derived factor 1 (P = 0.03) compared to those with lower Model of End-Stage Liver
Disease scores (<=15). The cluster of differentiation 34+ cell population was a
predictor for the development of sepsis (P < 0.001), and per unit loss increased
the probability of sepsis by 16%. Cirrhosis patients with fewer HSCs had lower
hemoglobin (P = 0.05) and platelet counts (P = 0.05) and showed early graft
dysfunction. CONCLUSIONS: Increasing severity of cirrhosis causes derangement of
the hematopoietic niche and loss of HSCs, contributing to the hematological and
immunological dysfunctions and reduced potential for regeneration; restoring BM
functions could provide new therapeutic options in cirrhosis. (Hepatology
2016;64:1273-1288).
PMID- 27486865
TI - The subperiosteal, drill hole, midface lift.
AB - This article describes a surgical technique using drill holes through the
inferior orbital rim and fixation with permanent sutures as a functional
subperiosteal midface lift and compares it to other standard midface elevation
techniques. This was a retrospective, comparative, non-randomized study. Charts
of all patients undergoing midface elevation between 2009 and 2013 were reviewed.
Pre- and post-operative photos were graded on a scale 0 to 3 with 0 representing
normal lower lid position and lid/cheek junction and 3 representing the most
severe malposition. Twenty-seven patients (35 sides) underwent midface lift.
Twelve sides had the subperiosteal drill hole midface lift; 9 preperiosteal with
Vicryl suture fixation to periosteum; 14 subperiosteal with Endotine midface B
device. All groups had similar demographics and indications for surgery. Average
follow-up time was greater than 4 months in all groups. No significant
complications were seen in any of the patients. The average post-operative grade
of the drill hole group was 0.65 compared to 0.75 of the preperiosteal Vicryl
group and 0.7 of the Endotine group. The drill hole group had the most severe pre
operative malposition. Overall, the drill hole group demonstrated the largest
improvement score. The subperiosteal drill hole technique proved to be an
effective method for functional midface elevation. This technique achieves
adequate and durable vertical elevation without relying on the strength of the
periosteum or use of a commercial device.
PMID- 27486866
TI - Longitudinal Erythronychia of the Fingernail.
PMID- 27486867
TI - The Role of a Vascular Surgeon.
PMID- 27486868
TI - Association between Elevated Hemoglobin A1c Levels and the Outcomes of Patients
with Small-Artery Occlusion: A Hospital-Based Study.
AB - INTRODUCTION: Abnormal glucose metabolism is an independent risk factor for poor
outcome following acute ischemic stroke. However, the relationship between
initial hemoglobin A1c level and functional outcome (defined by modified Rankin
Scale scores) following small-artery occlusion, a subtype of ischemic stroke, is
unknown. The aim of the present study was to evaluate this association among
patients diagnosed with small-artery occlusion. MATERIALS AND METHODS: Data on
793 patients diagnosed with small-artery occlusion from October 25, 2012 to June
30, 2015 were collected from the stroke registry of the Department of
Neurorehabilitation of HuanHu Hospital. Hemoglobin A1c values at admission were
classified into three groups according to tertiles (<5.9,5.9to<6.7, and>=6.7). We
used receiver operating characteristics curves to investigate the predictive
value of hemoglobin A1c and examined the relationship between hemoglobin A1c
levels at admission and modified Rankin Scale scores using univariate and
multivariate analyses. RESULTS: The area under the curve was 0.570 (95%CI, 0.509
0.631; P = 0.023). Patients in the highest HbA1c stratification (>=6.7) had a
significantly higher risk of an unfavorable outcome than patients in the lowest
stratification (<5.9; adjusted odds ratio, 2.099; 95%CI, 1.160-3.798; P = 0.014).
However, a significant association was not seen in the middle stratification (5.9
to <6.7; P = 0.115). CONCLUSIONS: Elevated hemoglobin A1c level on admission was
adversely associated with functional outcomes 3 months after stroke onset among
patients presenting with small-artery occlusion.
PMID- 27486869
TI - The Emerging Role of Tyrosine Kinase Inhibitors in Ovarian Cancer Treatment: A
Systematic Review.
AB - The present systematic review summarizes current evidence regarding the
mechanisms of action, the efficacy, and the adverse effects of tyrosine kinase
inhibitors (TKIs) in ovarian cancer patients. Phase II and III clinical trials
were sought in the PubMed database and in the Clinical Trials.gov registry
through September 30, 2015. Seventy-five clinical trials regarding TKIs targeting
mainly vascular endothelial growth factor receptor, epidermal growth factor
receptor, platelet-derived growth factor receptor, and sarcoma tyrosine kinase
(Src) were yielded. The most promising results were noted with cediranib,
nintedanib, and pazopanib. However, drawing universal conclusions about the
potential integration of TKIs in ovarian cancer therapy remains elusive.
Furthermore, emerging challenges and directions for the future research are
critically discussed.
PMID- 27486871
TI - The Miraprep: A Protocol that Uses a Miniprep Kit and Provides Maxiprep Yields.
AB - Plasmid purification is a basic tool of molecular biologists. Although the
development of plasmid isolation kits utilizing silica spin columns reduced the
time and labor spent on plasmid purification, achieving large plasmid DNA yields
still requires significant time and effort. Here we introduce the Miraprep, a
rapid protocol that allows isolation of plasmid DNA using commercial Miniprep
kits, but with DNA yields comparable to commercial Maxiprep plasmid
purifications. Combining ethanol precipitation with spin column purification, we
created a DNA isolation protocol that yields highly concentrated plasmid DNA
samples in less than 30 minutes. We show that Miraprep isolated plasmids are as
stable as plasmids isolated by standard procedures, can be used for standard
molecular biology procedures including DNA sequencing, and can be efficiently
transfected into mammalian cells. This new plasmid DNA isolation protocol will
significantly reduce time and labor without increasing costs.
PMID- 27486872
TI - Global DNA Methylation Changes in Nile Tilapia Gonads during High Temperature
Induced Masculinization.
AB - In some fish species, high or low temperature can switch the sex determination
mechanisms and induce fish sex reversal when the gonads are undifferentiated.
During this high or low temperature-induced sex reversal, the expressions of many
genes are altered. However, genome-wide DNA methylation changes in fish gonads
after high or low temperature treatment are unclear. Herein, we compared the
global DNA methylation changes in the gonads from control females (CF), control
males (CM), high temperature-treated females (TF), and high temperature-induced
males (IM) from the F8 family of Nile tilapia (Oreochromis niloticus) using
methylated DNA immunoprecipitation sequencing. The DNA methylation level in CF
was higher than that in CM for various chromosomes. Both females and males showed
an increase in methylation levels on various chromosomes after high-temperature
induction. We identified 64,438 (CF/CM), 63,437 (TF/IM), 98,675 (TF/CF), 235,270
(IM/CM) and 119,958 (IM/CF) differentially methylated regions (DMRs) in Nile
tilapia gonads, representing approximately 0.70% (CF/CM), 0.69% (TF/IM), 1.07%
(TF/CF), 2.56% (IM/CM), and 1.30% (IM/CF)of the length of the genome. A total of
89 and 65 genes that exhibited DMRs in their gene bodies and promoters were
mapped to the Nile tilapia genome. Furthermore, more than half of the genes with
DMRs in the gene body in CF/CM were also included in the IM/CM, TF/CF, TF/IM, and
IM/CF groups. Additionally, many important pathways, including neuroactive ligand
receptor interaction, extracellular matrix-receptor interaction, and biosynthesis
of unsaturated fatty acids were identified. This study provided an important
foundation to investigate the molecular mechanism of high temperature-induced sex
reversal in fish species.
PMID- 27486873
TI - CONIFER - Non-Interventional Study to Evaluate Therapy Monitoring During
Deferasirox Treatment of Iron Toxicity in Myelodysplastic Syndrome Patients with
Transfusional Iron Overload.
AB - BACKGROUND: The non-interventional study CONIFER was designed to assess the
safety and clinical practicability of deferasirox for the treatment of
transfusional iron overload in myelodysplastic syndrome (MDS) patients. METHODS:
Patients included in the study were diagnosed with MDS and received at least 1
treatment with deferasirox. The observation period covered the time from the
initial visit until the last follow-up. RESULTS: The data of 99 patients with MDS
scored mainly as International Prognostic Scoring System (IPSS) low and
intermediate 1 were evaluated. The mean age of the participants was 75 years and
58% of the patients were male. Iron overload was assessed by serum ferritin level
(mean baseline serum ferritin 2,080 +/- 1,244 ug/l). Patients were treated for a
mean duration of 16 months (mean daily dose at baseline 11.8 +/- 7.0 mg/kg).
Stratification of serum ferritin levels by deferasirox dose showed a reduction at
the higher but no reduction at the lower dose (< 15 mg/kg vs. >= 15 mg/kg and <
20 mg/kg vs. >= 20 mg/kg). The majority of patients (81%) were affected by at
least 1 adverse event, with decreased renal creatinine clearance being the most
frequent. CONCLUSION: Higher doses (>= 15 mg/kg) of deferasirox effectively and
safely reduced serum ferritin levels in MDS patients with transfusional iron
overload.
PMID- 27486874
TI - ENETS Newsletter.
PMID- 27486876
TI - Predictive value of pedicle involvement with MRI in spine metastases.
AB - OBJECTIVES: The study aimed to retrospectively evaluate the accuracy and value of
magnetic resonance imaging (MRI) in predicting pedicle involvement for patients
with spine metastases. METHODS: Forty-five patients with a vertebral metastasis
encroaching at least one pedicle were studied using MRI before surgery and
regularly after surgery. Patients were categorized on the basis of their numbers
of pedicle involvement (Group 1: one pedicle was involved, n = 23; Group 2: two
pedicles were involved, n = 22). The diagnostic accuracy was calculated, and
comparisons of intraoperative blood loss and recurrence rate between the two
groups were performed. RESULTS: The overall performance of MRI in predicting the
pedicle involvement was as follows: accuracy, 94.4%; sensitivity, 95.5%; and
specificity, 91.3%. Less intraoperative blood loss was observed for Group 1
compared with Group 2 (1,661 +/- 672 ml and 2,173 +/- 790 ml, respectively, P =
0.024). Tumor relapse occurred in 8.7% (2/23) of Group 1 and in 22.7% (5/22) of
Group 2 with median recurrence free survival time 14 and 9 months, respectively.
CONCLUSIONS: MRI is a reliable approach to assess pedicle involvement. It has
potential for use in the evaluation of the clinical characteristics of patients
with spine metastases.
PMID- 27486877
TI - A three-dimensional collagen scaffold cell culture system for screening anti
glioma therapeutics.
AB - Three-dimensional (3D) culture, which can simulate in vivo microenvironments, has
been increasingly used to study tumor cell biology. Since most preclinical anti
glioma drug tests still rely on conventional 2D cell culture, we established a
collagen scaffold for 3D glioma cell culture. Glioma cells cultured on these 3D
scaffolds showed greater degree of dedifferentiation and quiescence than cells in
2D culture. 3D-cultured cells also exhibited enhanced resistance to
chemotherapeutic alkylating agents, with a much higher proportion of glioma stem
cells and upregulation of O6-methylguanine DNA methyltransferase (MGMT).
Importantly, tumor cells in 3D culture showed chemotherapy resistance patterns
similar to those observed in glioma patients. Our results suggest that 3D
collagen scaffolds are promising in vitro research platforms for screening new
anti-glioma therapeutics.
PMID- 27486880
TI - Overexpressed LAPTM4B-35 is a risk factor for cancer recurrence and poor
prognosis in non-small-cell lung cancer.
AB - BACKGROUND: The expression levels and clinical significances of Lysosomal
associated protein transmembrane-4beta-35 (LAPTM4B-35) protein are unknown in the
non-small-cell lung cancer (NSCLC). This study aimed to explore the expression
and prognostic value of LAPTM4B-35 in NSCLC patients. METHODS: The
clinicopathological and survival data of 107 NSCLC patients who received radical
surgery from 2007 and 2011 were reviewed. The LAPTM4B-35 expression of the paired
tumors and adjacent normal specimens were detected, and the association between
LAPTM4B-35 and clinical variables was explored. Kaplan-Meier analysis and Cox
regression (Proportional hazard model) were performed to investigate the
prognostic significance for NSCLC. RESULTS: LAPTM4B-35 was over expressed in
NSCLC tissues. The elevated LAPTM4B-35 expression was associated with cancer
recurrence (P = 0.031). The 5-year median OS and PFS were significantly worse in
the LAPTM4B-35 overexpressed group. Multivariate Cox analysis showed that LAPTM4B
35 over-expression was an independent factor for OS and PFS in NSCLC(P = 0.018, P
= 0.026, respectively). CONCLUSIONS: The overexpressed LAPTM4B-35 was an
independent prognostic biomarker for NSCLC, which could predict cancer recurrence
and poor over survival. And that may be applied as potential target for NSCLC
treatment.
PMID- 27486879
TI - Consumption of pomegranates improves synaptic function in a transgenic mice model
of Alzheimer's disease.
AB - Alzheimer's Disease (AD) is a progressive neurodegenerative disorder
characterized by extracellular plaques containing abnormal Amyloid Beta (Abeta)
aggregates, intracellular neurofibrillary tangles containing hyperphosphorylated
tau protein, microglia-dominated neuroinflammation, and impairments in synaptic
plasticity underlying cognitive deficits. Therapeutic strategies for the
treatment of AD are currently limited. In this study, we investigated the effects
of dietary supplementation of 4% pomegranate extract to a standard chow diet on
neuroinflammation, and synaptic plasticity in APPsw/Tg2576 mice brain. Treatment
with a custom mixed diet (pellets) containing 4% pomegranate for 15 months
ameliorated the loss of synaptic structure proteins, namely PSD-95, Munc18-1, and
SNAP25, synaptophysin, phosphorylation of Calcium/Calmodulin Dependent Protein
Kinase IIalpha (p-CaMKIIalpha/ CaMKIIalpha), and phosphorylation of Cyclic AMP
Response Element Binding Protein (pCREB/CREB), inhibited neuroinflammatory
activity, and enhanced autophagy, and activation of the phophoinositide-3-kinase
Akt-mammalian target of rapamycin signaling pathway. These neuroprotective
effects were associated with reduced beta-site cleavage of Amyloid Precursor
Protein in APPsw/Tg2576 mice. Therefore, long-term supplementation with
pomegranates can attenuate AD pathology by reducing inflammation, and altering
APP-dependent processes.
PMID- 27486881
TI - The effect of radiotherapy in liver-confined but non-resectable Barcelona Clinic
Liver Cancer stage C large hepatocellular carcinoma.
AB - BACKGROUND AND AIMS: Clinical trials to determine the efficacy of radiotherapy
(RT) in liver-confined but non-resectable Barcelona Clinic Liver Cancer (BCLC)
stage C hepatocellular carcinoma (HCC) are scarce. We aimed to determine the
benefit of RT in such tumors and investigated large HCC tumors. METHODS: HCC data
from the Korea Central Cancer Registry recorded from 2008 to 2010 were used. A
total of 593 patients met our inclusion criteria; 67 were treated with RT while
the remainder made up the non-RT group. Fifty-two RT recipients underwent
combination treatments within 4 weeks after the first RT treatment, and were
defined as the combination RT group. We performed propensity score matching (PSM)
to compare the RT or combination RT groups with the non-RT group. The endpoint
was overall survival (OS). RESULTS: Median follow-up time for surviving patients
was 48 months. After PSM, there was no difference in OS between the RT and non-RT
groups or between the combination RT and non-RT groups. However, the combination
RT group had a longer median survival time (MST) (10.7 vs. 6.9 months,
respectively). Next, we conducted PSM between the combination RT and non-RT
groups in patients with tumor sizes >=10 cm; MST was significantly longer in the
former group (10.1 vs. 5.4 months, respectively; bootstrap 95% confidence
interval of the difference in MST: 0.2-11.8). CONCLUSIONS: As a combined
modality, RT is a plausible therapeutic option for liver-confined but non
resectable BCLC stage C large HCC patients.
PMID- 27486882
TI - Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a
virological and clinical study.
AB - AIM: To evaluate the virological and clinical characteristics of occult HBV
infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven
cirrhosis and HCC. METHODS: HBV DNA was sought and sequenced in plasma, HCC
tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x
regions. OBI was identified by the presence of HBV DNA in at least two different
PCRs. RESULTS: OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC
liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti
HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc
positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients
with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C
cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p
< 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino
acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in
positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P,
G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region
(P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the
S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different.
CONCLUSIONS: The study showed a significant correlation between OBI and the
severity of liver damage, several patterns of mutations in the S, pre-S1 and pre
S2 regions in HCC tissue, some at their first description.
PMID- 27486883
TI - Validation of prognostic scoring and assessment of clinical benefit for patients
with bone sarcomas enrolled in phase I clinical trials.
AB - BACKGROUND: We sought to validate the Royal Marsden Hospital (RMH) and MD
Anderson Cancer Center (MDACC) prognostic scoring systems for the selection of
bone sarcoma patients for phase I clinical trials and to identify additional risk
factors related to survival. PATIENTS AND METHODS: We retrospectively reviewed
the baseline characteristics and outcomes of 92 bone sarcoma patients who were
referred to MDACC's Phase I Clinical Trials Program. RESULTS: Ninety-two patients
with Ewing sarcoma (N = 47), osteosarcoma (N = 22), chondrosarcoma (N = 16), and
other tumors (N = 7) were evaluated; 78 were enrolled in at least 1 of 43
different phase I trials. The median overall survival (OS) was 8.8 months (95%
confidence interval [CI] = 6.8-13.7 months). Independent factors that predicted
shorter survival were male sex, >2 metastatic sites, >3 previous therapies,
hemoglobin level <10.5 g/dL, platelet count >200 x103/L, creatinine level >=1.3
mg/dL, and lactate dehydrogenase level >ULN. Patients with good RMH scores (0-1)
had longer OS than patients with poor RMH scores (2-3) (HR = 5.8, 95% CI = 2.9
11.0; P < 0.0001), as did patients with low MDACC scores (0-1) as compared to
patients with higher MDACC scores (2-4) (HR = 3.2, 95% CI = 1.9-5.6; P < 0.0001).
CONCLUSION: The RMH prognostic score can be used to predict the OS of bone cancer
patients referred for phase I trials. The MDACC score added no value to the RMH
score and therefore does not have a role in assessment of patients with bone
tumors. Patients with advanced bone sarcomas should be considered for phase I
trials.
PMID- 27486885
TI - Inherent low Erk and p38 activity reduce Fas Ligand expression and degranulation
in T helper 17 cells leading to activation induced cell death resistance.
AB - Activation Induced Cell Death of T helper cells is central to maintaining immune
homeostasis and a perturbation often manifests in aberrant T helper cells that is
associated with immunopathologies. Significant presence of T cells positive for
IL-17A (Th17) and dual positive for IFN-gamma/IL-17A (Th1/Th17) in both effector
(CD45RA+RO+) and memory (CD45RA-RO+) compartments with differential FasL protein
in RA peripheral blood suggested their differential TCR AICD sensitivity. Lowered
active caspase-3 in Th17 and Th1/Th17 over Th1 cells confirmed their capability
to resist AICD and pointed to early upstream events. Differential MAPK
activities, FasL protein and downstream caspase-3 activities in murine Th1 and
Th17 cells established distinct TCR mediated signaling pathways and suggested low
Erk and p38 activity as pivotal for AICD sensitivity. We extrapolated our mouse
and human data and report that Fas-FasL is the preferred death pathway for both
Th1 and Th17 and that inherently low Erk2 activity protected Th17 cells from TCR
AICD. The presence of significantly higher numbers of aberrant T helper cells in
RA also suggest an inflammatory cytokine milieu and AICD insensitive T cell link
to sustained inflammation. Re sensitization to apoptosis by targeting MAPK
activity especially Erk2 in RA might be of therapeutic value.
PMID- 27486887
TI - Differences in Patient Characteristics among Men Choosing Open or Robot-Assisted
Radical Prostatectomy in Contemporary Practice - Analysis of Surveillance,
Epidemiology, and End Results Database.
AB - OBJECTIVE: To examine characteristics of robot-assisted (RARP) and open radical
prostatectomy (ORP) patients. PATIENTS AND METHODS: We relied on the
Surveillance, Epidemiology, and End Results-Medicare-linked database and focused
on prostate cancer patients between 2008 and 2009. In multivariable logistic
regression analyses, we predicted RARP. RESULTS: Of 5,915 patients, 3,476 (58.8%)
underwent RARP and 2,439 (41.2%) ORP. Patients within intermediate (OR 1.4, p =
0.01) or highest (OR 1.5, p = 0.02) education strata and those treated by
surgeons with a high volume (OR 2.2, p < 0.001) were more likely to undergo RARP.
Conversely, those residing in rural areas (OR 0.7, p = 0.005) and those with
clinical stage T2 or higher (OR 0.7, p = 0.006) were less likely to undergo RARP.
Additionally, patients from the Southwest were less likely to undergo RARP (OR
0.4, p < 0.001), but those from the Northern Plains were more likely to undergo
RARP (OR 1.4, p = 0.02) than their counterparts from the East. Finally, RARP
patients were neither younger nor healthier than ORP patients. CONCLUSIONS:
Several patient characteristics such as education, region of residence and
population density affect the likelihood of RARP vs. ORP treatment. Similarly,
clinical stage and surgeon characteristics also affect the assignment to one or
other treatment modality.
PMID- 27486888
TI - Screening of Variations in CD22 Gene in Children with B-Precursor Acute
Lymphoblastic Leukemia.
AB - BACKGROUND: CD22 is expressed on the surface of B-cell lineage cells from the
early progenitor stage of pro-B cell until terminal differentiation to mature B
cells. It plays a role in signal transduction and as a regulator of B-cell
receptor signaling in B-cell development. OBJECTIVES: We aimed to screen exons 9
14 of the CD22 gene, which is a mutational hot spot region in B-precursor acute
lymphoblastic leukemia (pre-B ALL) patients, to find possible genetic variants
that could play role in the pathogenesis of pre-B ALL in Turkish children.
METHODS: This study included 109 Turkish children with pre-B ALL who were
diagnosed at Losante Hospital for Children with Leukemia. Genomic DNA was
extracted from both peripheral blood and bone marrow leukocytes. Gene
amplification was performed with PCR, and all samples were screened for the
variants by single strand conformation polymorphism. Samples showing band shifts
were sequenced on an automated sequencer. RESULTS: In our patient group a total
of 9 variants were identified in the CD22 gene by sequencing: a novel variant in
intron 10 (T2199G); a missense variant in exon 12; 5 intronic variants between
exon 12 and intron 13; a novel intronic variant (C2424T); and a synonymous in
exon 13. Thirteen of 109 children (11.9%) carried the T2199G novel intronic
variant located in intron 10, and 17 of 109 children (15.6%) carried the C2424T
novel intronic variant. CONCLUSION: Novel variants in the CD22 gene in children
with pre-B ALL in Turkey that are not present, in the Human Gene Mutation
Database or NCBI SNP database, were found.
PMID- 27486890
TI - Unidirectional Fast Growth and Forced Jumping of Stretched Droplets on
Nanostructured Microporous Surfaces.
AB - Superhydrophobic nanostructured surfaces have demonstrated outstanding capability
in energy and water applications by promoting dropwise condensation, where fast
droplet growth and efficient condensate removal are two key parameters. However,
these parameters remain contradictory. Although efficient droplet removal is
easily obtained through coalescence jumping on uniform superhydrophobic surfaces,
simultaneously achieving fast droplet growth is still challenging. Also, on such
surfaces droplets can grow to larger sizes without restriction if there is no
coalescence. In this work, we show that superhydrophobic nanostructured
microporous surfaces can manipulate the droplet growth and jumping. Microporous
surface morphology effectively enhances the growth of droplets in pores owing to
large solid-liquid contact area. At low supersaturations, the upward growth rate
(1-1.5 MUm/s) of these droplets in pores is observed to be around 15-25 times
that of the droplets outside the pores. Meanwhile, their top curvature radius
increases relatively slowly (~0.25 MUm/s) due to pore confinement, which results
in a highly stretched droplet surface. We also observed forced jumping of
stretched droplets in pores either through coalescence with spherical droplets
outside pores or through self-pulling without coalescence. Both experimental
observation and theoretical modeling reveal that excess surface free energy
stored in the stretched droplet surface and micropore confinement are responsible
for this pore-scale-forced jumping. These findings reveal the insightful physics
of stretched droplet dynamics and offer guidelines for the design and fabrication
of novel super-repellent surfaces with microporous morphology.
PMID- 27486889
TI - The Criminal Justice Experience of African American Cocaine Users in Arkansas.
AB - BACKGROUND: African Americans are incarcerated at rates much higher than other
racial and ethnic groups in the United States. OBJECTIVES: We sought to
qualitatively explore the relationships between ongoing involvement in the
criminal justice system and continued drug use in a population of urban and rural
African American cocaine users in a southern state. METHODS: Semi-structured
qualitative interviews were conducted among African American cocaine users in
Arkansas between 2010 and 2012. Participants resided in both rural (two counties
located in the eastern Arkansas Mississippi delta region) and urban (the county
including the capital city of Little Rock) areas. RESULTS: Numerous important
themes emerged from participants' narratives, including chronic involvement with
the criminal justice system (being a "career criminal"), continued access to
drugs while incarcerated, relapse, and reincarceration and lack of access to
effective drug treatment. Conclusion/Importance: The themes which emerged from
our data speak to the collective experience that many substance using populations
in the United States face in dealing with the criminal justice system. Our
findings highlight the need to better, more holistic ways of engaging African
American substance users in community based substance use treatment and
supportive services.
PMID- 27486891
TI - Micellar Effects on Photoinduced Electron Transfer in Aqueous Solutions
Revisited: Dramatic Enhancement of Cage Escape Yields in Surfactant Ru(II)
Diimine Complex/[Ru(NH3)6](2+) Systems.
AB - The effect of cationic micelle incorporation on light induced electron transfer,
charge separation and back electron transfer between an aqueous electron donor,
[Ru(NH3)6](2+), and a series of Ru(II) diimine complex chromophores/acceptors, is
presented. The chromophores have the general formula [(bpy)2Ru(LL)](2+) (LL =
bpy; 4-R-4'-methyl-2,2'-bpy, R = pentyl (MC5), terdecyl (MC13), heptadecyl
(MC17); 4,4'-di(heptadecyl)-2,2'-bpy (DC17)). Of the five chromophores, the MC13,
MC17, and DC17 complexes associate with the added micelle forming surfactant,
cetyltrimethylammonium bromide (CTAB). Quenching of the luminescence of the bpy
and MC5 complexes by [Ru(NH3)6](2+) is unaffected by addition of surfactant,
while rate constants for quenching of the MC13 and MC17 complexes are decreased.
Cage escape yields following photoinduced electron transfer to generate
[(bpy)2Ru(LL)](+) and [Ru(NH3)6](3+) are approximately 0.1 for all the water
soluble chromophores (excluding DC17) in the absence of added CTAB. In the
presence of surfactant, the cage escape yields dramatically increase for the MC13
(0.4) and MC17 (0.6) complexes, while remaining unchanged for [Ru(bpy)3](2+) and
the MC5 complex. Back electron transfer of the solvent separated ions is also
strongly influenced by the presence of surfactant. For the MC13 and MC17
complexes, back electron transfer rate constants decrease by factors of 270 and
190, respectively. The MC5 complex exhibits two component back electron transfer,
with the fast component having a rate constant close to that in the absence of
surfactant and a slow component nearly 200 times smaller. Results are interpreted
in terms of the partitioning of the 2+ and 1+ forms of the chromophores between
aqueous and micellar phases. The extended lifetimes of the radical ions may prove
useful in coupling the strong reductants formed to kinetically facile catalysts
for reduction of water to hydrogen.
PMID- 27486892
TI - Isolated Bilateral Lacrimal Gland Agenesis.
AB - A 5-year-old boy presented to the ophthalmology department complaining of absent
tearing while crying. Slit-lamp examination showed decreased tear margin film
with normal punctae. Orbit magnetic resonance imaging was done and showed
bilateral absent lacrimal glands. This is the third case of isolated bilateral
lacrimal gland agenesis in the literature. [J Pediatr Ophthalmol Strabismus.
2016;53:e35-e38.].
PMID- 27486893
TI - Familial Exudative Vitreoretinopathy With a Novel LRP5 Mutation.
AB - This report reviews the genetics of familial exudative vitreoretinopathy (FEVR)
and describes the identification of a novel variant in the LRP5 gene. A 20-month
old boy presented with reduced visual acuity in the right eye from exudative
retinal detachment with mild retinal traction. Fluorescein angiography in the
right eye disclosed extensive peripheral retinal non-perfusion and telangiectatic
vessels and the left eye showed minimal peripheral non-perfusion. These features
were suggestive of FEVR. Treatment with laser photocoagulation and cryotherapy to
the region of non-perfusion was performed with resolution of the exudative
retinal detachment. Fundus examination of the father revealed mild signs of FEVR,
such as hyperacute retinal vascular branching and slight retinal vascular
traction, whereas the mother's fundus examination was unremarkable. Genetic
testing revealed that the affected boy was negative for mutations in the FZD4,
NDP, and TSPAN12 genes and heterozygous for a previously unreported A745V variant
in the LRP5 gene. The father was also heterozygous for the A745V variant in the
LRP5 gene and the unaffected mother showed no mutation. A genetic evaluation of
the known genes associated with FEVR revealed a novel variant in the LRP5 gene
that co-segregated with the phenotype in the family. [J Pediatr Ophthalmol
Strabismus. 2016;53:e39-e42.].
PMID- 27486894
TI - Intra-arterial Chemotherapy for Adult Onset Retinoblastoma in a 32-Year-Old Man.
AB - A 32-year-old man with active unilateral group D retinoblastoma that was
recurrent following external beam radiotherapy was treated with intra-arterial
chemotherapy, leading to tumor regression. Additional plaque radiotherapy and
intravitreal chemotherapy were required for complete control. Final visual acuity
was 20/40. In selected cases, adult-onset retinoblastoma can be managed with
intra-arterial chemotherapy. [J Pediatr Ophthalmol Strabismus. 2016;53:e43-e46.].
PMID- 27486895
TI - Trends in Receipt of Mental Health Treatments Among Adults in the United States,
2008-2013.
AB - OBJECTIVE: This study examined trends in the 12-month prevalence of receiving
mental health treatments among adults 18 years or older and among different
generational cohorts in the United States between 2008 and 2013. METHODS: We
examined data from 274,900 persons 18 years or older who participated in the 2008
2013 National Surveys on Drug Use and Health (then linked to the 2011-2014 Area
Health Resources Files at the county level). Multivariable logistic regressions
were applied to assess trends in the model-adjusted prevalence of receiving
mental health treatments. RESULTS: Between 2008 and 2013, the 12-month prevalence
of mental illness (MI) remained stable in adults 18 years or older in the United
States and in each of the examined generational cohorts. Receipt of psychotropic
medications without inpatient or outpatient treatment increased in the overall
adult population, baby boomers with MI, and Generation X with MI. The increase
was 23.8% (6.3% to 7.8%, P < .001) among all adults, 28.4% (20.4% to 26.2%, P =
.010) among baby boomers with MI, and 34.7% (14.7% to 19.8%, P = .001) among
Generation X with MI. Among the Silent Generation with MI, receipt of mental
health treatments remained unchanged. CONCLUSIONS: The prevalence of receiving
psychotropic medications without inpatient or outpatient treatment increased
among the overall adult population, baby boomers with MI, and Generation X with
MI between 2008 and 2013. With the ongoing mental health parity and health reform
efforts, further studies are warranted to monitor trends in mental health
treatment in these populations.
PMID- 27486896
TI - Correction: Durations and Delays in Care Seeking, Diagnosis and Treatment
Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.
AB - [This corrects the article DOI: 10.1371/journal.pone.0152287.].
PMID- 27486897
TI - Identification of temporal factors related to shot performance for indoor recurve
archery.
AB - The purpose of this study was to investigate the temporal phases of the archery
shot cycle that distinguish the arrows distance from centre, in an attempt to
understand critical factors that affect performance. Fifteen archers of varying
ability each performed 30 shots at 18 m. Fourteen potential predictor variables
were measured for statistical modelling by stepwise multiple linear regression.
The results show that pre-shot time (pre-performance routine), follow-through
time (post-performance routine), aiming time, speed of the arrow and the
%variation in clicker-release time, account for 7.7% of the variation in
predicting shot performance. The results have implications for practice
demonstrating factors that coaches should focus on to develop their athletes.
Further work on pre-, but more importantly, post-performance routines are needed
generally within sport research as they are lacking and have been shown to be
important contributing factors in a number of sports.
PMID- 27486898
TI - Apolipoprotein E Genotype Linked to Spatial Gait Characteristics: Predictors of
Cognitive Dual Task Gait Change.
AB - BACKGROUND: Developing measures to detect preclinical Alzheimer's Disease is
vital, as prodromal stage interventions may prove more efficacious in altering
the disease's trajectory. Gait changes may serve as a useful clinical heuristic
that precedes cognitive decline. This study provides the first systematic
investigation of gait characteristics relationship with relevant demographic,
physical, genetic (Apolipoprotein E genotype), and health risk factors in non
demented older adults during a cognitive-load dual task walking condition.
METHODS: The GAITRite system provided objective measurement of gait
characteristics in APOE-e4 "carriers" (n = 75) and "non-carriers" (n = 224).
Analyses examined stride length and step time gait characteristics during simple
and dual-task (spelling five-letter words backwards) conditions in relation to
demographic, physical, genetic, and health risk factors. RESULTS: Slower step
time and shorter stride length associated with older age, greater health risk,
and worse physical performance (ps < .05). Men and women differed in height, gait
characteristics, health risk factors and global cognition (ps < .05). APOE-e4
associated with a higher likelihood of hypercholesterolemia and overall illness
index scores (ps < .05). No genotype-sex interactions on gait were found. APOE-e4
was linked to shorter stride length and greater dual-task related disturbances in
stride length. CONCLUSIONS: Stride length has been linked to heightened fall
risk, attention decrements and structural brain changes in older adults. Our
results indicate that stride length is a useful behavioral marker of cognitive
change that is associated with genetic risk for AD. Sex disparities in motor
decline may be a function of health risk factors.
PMID- 27486900
TI - Synthesis of a Small-Molecule Library with Skeletal Diversity from Hemslecin A
via the Reaction-Discovery Strategy.
AB - An efficient reaction tool box was developed for the synthesis of skeletally
diverse and stereochemically complex templates for a small-molecule library based
on the common synthon Q, which was prepared from hemslecin A in four steps. The
reaction tool box comprises three acid-promoted rearrangements: semipinacol,
Wagner-Meerwein, and cyclopropylmethyl cation rearrangements. More importantly, a
Mn-mediated C-H oxidation was developed to achieve a high level of complexity,
which provides a new entry for C-H functionalization of inert angular methyl
groups in the chemistry of triterpenes. Our reaction-discovery strategy based on
hemslecin A provides a basis for the inherent chemistry of triterpenes and could
be applied for the further transformation of triterpenes.
PMID- 27486899
TI - The Association between the Cross-Sectional Area of the Dural Sac and Low Back
Pain in a Large Population: The Wakayama Spine Study.
AB - OBJECTIVE: The purpose of this study was to evaluate the relations between the
degree of encroachment, measured as the cross-sectional area of the dural sac,
and low back pain in a large population. METHODS: In this cross-sectional study,
data from 802 participants (247 men, 555 women; mean age, 63.5 years) were
analyzed. The measurement of the cross-sectional area of the dural sac from the
level of L1/2 to L4/5 was taken using axial T2-weighted images. The minimum cross
sectional area was defined as the cross-sectional area of the dural sac at the
most constricted level in the examined spine. Participants were divided into
three groups according to minimum cross-sectional area measurement quartiles
(less than the first quartile, between the first and third quartiles, and greater
than the third quartile). A multivariate logistic regression analysis was used to
estimate the association between the minimum cross-sectional area and the
prevalence of low back pain. RESULTS: The mean minimum cross-sectional area was
117.3 mm2 (men: 114.4 mm2; women: 118.6 mm2). A logistic regression analysis
adjusted for age, sex, body mass index, and other confounding factors, including
disc degeneration, showed that a narrow minimum cross-sectional area (smaller
than the first quartile) was significantly associated with low back pain (odds
ratio, 1.78; 95% confidence interval, 1.13-2.80 compared to the wide minimum
cross-sectional area group: minimum cross-sectional area greater than the third
quartile measured). CONCLUSION: This study showed that a narrow dural sac cross
sectional area was significantly associated with the presence of low back pain
after adjustment for age, sex, and body mass index. Further investigations that
include additional radiographic findings and psychological factors will continue
to elucidate the causes of low back pain.
PMID- 27486901
TI - HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem
cells.
AB - OBJECTIVE: Glioblastoma multiforme (GBM) develops from a small subpopulation of
stem-like cells, which are endowed with the ability to self-renew, proliferate
and give rise to progeny of multiple neuroepithelial lineages. These cells are
resistant to conventional chemo- and radiotherapy and are hence also responsible
for tumor recurrence. HMGA1 overexpression has been shown to correlate with
proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of
cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is
not completely understood. RESEARCH DESIGN AND METHODS: We have investigated the
role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and
resistance to temozolomide by shRNA- mediated HMGA1 silencing. RESULTS: We first
report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs.
Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming
efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly,
HMGA1 silencing also leads to reduced tumor initiation ability in vivo.
CONCLUSIONS: These results demonstrate a pivotal role of HMGA1 in cancer stem
cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM
therapy.
PMID- 27486902
TI - Comparison of Keyes Punch Biopsy Instrument with Cervical Punch Biopsy Forceps
for Diagnosing Cervical Lesions.
AB - OBJECTIVE: To assess the feasibility and efficacy of Keyes punch biopsy
instrument (KP) in diagnosing cervical lesions and compare it with cervical punch
biopsy forceps (CP). METHODS: 75 women having satisfactory colposcopy with
abnormal transformation zone were included and paired colposcopic directed
biopsies were taken using KP followed by CP from the same target area. RESULTS:
It was feasible in all cases to take cervical biopsy with KP after increasing its
effective length. The volume of gross specimen obtained by KP was less than CP
(0.076 +/- 0.097 vs. 0.101 +/- 0.156 cm3, p = 0.061), however on microscopic
examination, mean length and mean depth of tissue in KP was greater than CP by
0.06 mm (p = 0.810) and 0.14 mm (p = 0.634) respectively. Exact agreement was
found with the final surgical specimen in 42% of cases in both the biopsy
forceps. CONCLUSION: KP is almost at par with CP for diagnosing preinvasive
cervical lesions and is a useful adjunct to the existing armamentarium of biopsy
forceps.
PMID- 27486904
TI - Biomechanical Factors in the Adaptations of Insect Tibia Cuticle.
AB - Insects are among the most diverse groups of animals on Earth. Their cuticle
exoskeletons vary greatly in terms of size and shape, and are subjected to
different applied forces during daily activities. We investigated the
biomechanics of the tibiae of three different insect species: the desert locust
(Schistocerca gregaria), American cockroach (Periplaneta americana) and Death's
Head cockroach (Blaberus discoidalis). In a previous work, we showed that these
tibiae vary not only in geometry (length, radius and thickness) but also in
material quality (Young's modulus) and in the applied stress required to cause
failure when loaded in bending. In the present work we used kinematic data from
the literature to estimate the forces and stresses arising in vivo for various
different activities, and thus calculated factors of safety defined as the ratio
between the failure stress and the in vivo stress, adjusting the failure stress
to a lower value to allow for fatigue failure in the case of frequently repeated
activities. Factors of safety were found to vary considerably, being as little as
1.7 for the most strenuous activities, such as jumping or escaping from tight
spaces. Our results show that these limbs have evolved to the point where they
are close to optimal, and that instantaneous failure during high-stress
activities is more critical than long-term fatigue failure. This work contributes
to the discussion on how form and material properties have evolved in response to
the mechanical functions of the same body part in different insects.
PMID- 27486903
TI - White Adipose Tissue Browning in the R6/2 Mouse Model of Huntington's Disease.
AB - Huntington's disease (HD) is a fatal, autosomal dominantly inherited
neurodegenerative disorder, characterised not only by progressive cognitive,
motor and psychiatric impairments, but also of peripheral pathology. In both
human HD and in mouse models of HD there is evidence of increased energy
expenditure and weight loss, alongside altered body composition. Unlike white
adipose tissue (WAT), brown adipose tissue (BAT), as well as brown-like cells
within WAT, expresses the mitochondrial protein, uncoupling protein 1 (UCP1).
UCP1 enables dissociation of cellular respiration from ATP utilization, resulting
in the release of stored energy as heat. Hyperplasia of brown/beige cells in WAT
has been suggested to enhance energy expenditure. In this study, we therefore
investigated the gene expression profile, histological appearance, response to
cold challenge and functional aspects of WAT in the R6/2 HD mouse model and
selected WAT gene expression in the full-length Q175 mouse model of HD. WAT from
R6/2 mice contained significantly more brown-like adipocyte regions and had a
gene profile suggestive of the presence of brown-like adipocytes, such as higher
Ucp1 expression. Cold exposure induced Ucp1 expression in R6/2 inguinal WAT to a
markedly higher degree as compared to the thermogenic response in WT WAT.
Alongside this, gene expression of transcription factors (Zfp516 and Pparalpha),
important inducers of WAT browning, were increased in R6/2 inguinal WAT, and
Creb1 was highlighted as a key transcription factor in HD. In addition to
increased WAT Ucp1 expression, a trend towards increased mitochondrial oxygen
consumption due to enhanced uncoupling activity was found in inguinal R6/2 WAT.
Key gene expressional changes (increased expression of (Zfp516 and Pparalpha))
were replicated in inguinal WAT obtained from Q175 mice. In summary, for the
first time, we here show that HD mouse WAT undergoes a process of browning,
resulting in molecular and functional alterations that may contribute to the
weight loss and altered metabolism observed with disease progression.
PMID- 27486905
TI - Olsalazine-Based Metal-Organic Frameworks as Biocompatible Platforms for H2
Adsorption and Drug Delivery.
AB - The drug olsalazine (H4olz) was employed as a ligand to synthesize a new series
of mesoporous metal-organic frameworks that are expanded analogues of the well
known M2(dobdc) materials (dobdc(4-) = 2,5-dioxido-1,4-benzenedicarboxylate; M
MOF-74). The M2(olz) frameworks (M = Mg, Fe, Co, Ni, and Zn) exhibit high surface
areas with large hexagonal pore apertures that are approximately 27 A in
diameter. Variable temperature H2 adsorption isotherms revealed strong adsorption
at the open metal sites, and in situ infrared spectroscopy experiments on
Mg2(olz) and Ni2(olz) were used to determine site-specific H2 binding enthalpies.
In addition to its capabilities for gas sorption, the highly biocompatible
Mg2(olz) framework was also evaluated as a platform for the delivery of
olsalazine and other encapsulated therapeutics. The Mg2(olz) material (86 wt %
olsalazine) was shown to release the therapeutic linker through dissolution of
the framework under simulated physiological conditions. Furthermore, Mg2(olz) was
used to encapsulate phenethylamine (PEA), a model drug for a broad class of
bioactive compounds. Under simulated physiological conditions, Mg2(olz)(PEA)2
disassembled to release PEA from the pores and olsalazine from the framework
itself, demonstrating that multiple therapeutic components can be delivered
together at different rates. The low toxicity, high surface areas, and
coordinatively unsaturated metal sites make these M2(olz) materials promising for
a range of potential applications, including drug delivery in the treatment of
gastrointestinal diseases.
PMID- 27486906
TI - Platinum-induced hearing loss after treatment for childhood cancer.
AB - BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin, oxaliplatin
or a combination of these, is used to treat a variety of paediatric malignancies.
Unfortunately, one of the most important adverse effects is the occurrence of
hearing loss or ototoxicity. There is a wide variation in the reported prevalence
of platinum-induced ototoxicity and the associated risk factors. More insight
into the prevalence of and risk factors for platinum-induced hearing loss is
essential in order to develop less ototoxic treatment protocols for the future
treatment of children with cancer and to develop adequate follow-up protocols for
childhood cancer survivors treated with platinum-based therapy. OBJECTIVES: To
evaluate the existing evidence on the association between childhood cancer
treatment including platinum analogues and the occurrence of hearing loss. SEARCH
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
(2015, Issue 8), MEDLINE (PubMed) (1945 to 23 September 2015) and EMBASE (Ovid)
(1980 to 23 September 2015). In addition, we searched reference lists of relevant
articles and the conference proceedings of the International Society for
Paediatric Oncology (2008 to 2014), the American Society of Pediatric
Hematology/Oncology (2008 to 2015) and the International Conference on Long-Term
Complications of Treatment of Children and Adolescents for Cancer (2010 to 2015).
Experts in the field provided information on additional studies. SELECTION
CRITERIA: All study designs, except case reports, case series (i.e. a description
of non-consecutive participants) and studies including fewer than 100
participants treated with platinum-based therapy who had an ototoxicity
assessment, examining the association between childhood cancer treatment
including platinum analogues and the occurrence of hearing loss. DATA COLLECTION
AND ANALYSIS: Two review authors independently performed the study selection. One
review author performed data extraction and risk of bias assessment, which was
checked by another review author. MAIN RESULTS: We identified 13 eligible cohort
studies including 2837 participants with a hearing test after treatment with a
platinum analogue for different types of childhood cancers. All studies had
methodological limitations, with regard to both internal (risk of bias) and
external validity. Participants were treated with cisplatin, carboplatin or both,
in varying doses. The reported prevalence of hearing loss varied considerably
between 0% and 90.1%; none of the studies provided data on tinnitus. Three
studies reported a prevalence of 0%, but none of these studies provided a
definition for hearing loss and there might be substantial or even complete
overlap in included participants between these three studies. When only studies
that did provide a definition for hearing loss were included, the prevalence of
hearing loss still varied widely between 1.7% and 90.1%. All studies were very
heterogeneous with regard to, for example, definitions of hearing loss, used
diagnostic tests, participant characteristics, (prior) anti-tumour treatment,
other ototoxic drugs and length of follow-up. Therefore, pooling of results was
not possible.Only two studies included a control group of people who had not
received platinum treatment. In one study, the prevalence of hearing loss was
67.1% (95% confidence interval (CI) 59.3% to 74.1%) in platinum-treated
participants, while in the control participants it was 7.4% (95% CI 6.2% to
8.8%). However, hearing loss was detected by screening in survivors treated with
platinum analogues and by clinical presentation in control participants. It is
uncertain what the effect of this difference in follow-up/diagnostic testing was.
In the other study, the prevalence of hearing loss was 20.1% (95% CI 17.4% to
23.2%) in platinum-treated participants and 0.4% (95% CI 0.12% to 1.6%) in
control participants. As neither study was a randomized controlled trial or
controlled clinical trial, the calculation of a risk ratio was not feasible as it
is very likely that both groups differed more than only the platinum
treatment.Only two studies evaluated possible risk factors using multivariable
analysis. One study identified a significantly higher risk of hearing loss in
people treated with cisplatin 400 mg/m(2) plus carboplatin 1700 mg/m(2) as
compared to treatment with cisplatin 400 mg/m(2) or less, irrespective of the
definition of hearing loss. They also identified a significantly higher risk of
hearing loss in people treated with non-anthracycline aminoglycosides antibiotics
(using a surrogate marker) as compared to people not treated with them, for three
out of four definitions of hearing loss. The other study reported that age at
treatment (odds ratio less than 1 for each single-unit increase) and single
maximum cisplatin dose (odds ratio greater than 1 for each single-unit increase)
were significant predictors for hearing loss, while gender was not. AUTHORS'
CONCLUSIONS: This systematic review shows that children treated with platinum
analogues are at risk for developing hearing loss, but the exact prevalence and
risk factors remain unclear. There were no data available for tinnitus. Based on
the currently available evidence we can only advise that children treated with
platinum analogues are screened for ototoxicity in order to make it possible to
diagnose hearing loss early and to take appropriate measures. However, we are
unable to give recommendations for specific follow-up protocols including
frequency of testing. Counselling regarding the prevention of noise pollution can
be considered, such as the use of noise-limiting equipment, avoiding careers with
excess noise and ototoxic medication. Before definitive conclusions on the
prevalence and associated risk factors of platinum-induced ototoxicity can be
made, more high-quality research is needed. Accurate and transparent reporting of
findings will make it possible for readers to appraise the results of these
studies critically.
PMID- 27486907
TI - Spirometry reference values for a Kyrgyz population.
PMID- 27486908
TI - Increased Airport Scrutiny by the Transportation Security Administration of a
Patient-Passenger Carrying Ammonium Lactate-Containing Moisturizer.
PMID- 27486909
TI - Identification of Rosmarinic Acid-Adducted Sites in Meat Proteins in a Gel Model
under Oxidative Stress by Triple TOF MS/MS.
AB - Triple TOF MS/MS was used to identify adducts between rosmarinic acid (RosA)
derived quinones and meat proteins in a gel model under oxidative stress. Seventy
five RosA-modified peptides responded to 67 proteins with adduction of RosA. RosA
conjugated with different amino acids in proteins, and His, Arg, and Lys adducts
with RosA were identified for the first time in meat. A total of 8 peptides
containing Cys, 14 peptides containing His, 48 peptides containing Arg, 64
peptides containing Lys, and 5 peptides containing N-termini that which
participated in adduction reaction with RosA were identified, respectively.
Seventy-seven adduction sites were subdivided into all adducted proteins
including 2 N-terminal adduction sites, 3 Cys adduction sites, 4 His adduction
sites, 29 Arg adduction sites, and 39 Lys adduction sites. Site occupancy
analyses showed that approximately 80.597% of the proteins carried a single RosA
modified site, 14.925% retained two sites, 1.492% contained three sites, and the
rest 2.985% had four or more sites. Large-scale triple TOF MS/MS mapping of RosA
adducted sites reveals the adduction regulations of quinone and different amino
acids as well as the adduction ratios, which clarify phenol-protein adductions
and pave the way for industrial meat processing and preservation.
PMID- 27486910
TI - Cost-Benefit Analysis of Three-Dimensional Craniofacial Models for Midfacial
Distraction: A Pilot Study.
AB - OBJECTIVE: Patient-specific three-dimensional (3D) models are increasingly used
to virtually plan rare surgical procedures, providing opportunity for
preoperative preparation, better understanding of individual anatomy, and implant
prefabrication. The purpose of this study was to assess the benefit of 3D models
related to patient safety, operative time, and cost. DESIGN: Retrospective
review. SETTING: Academic, tertiary care hospital. PATIENTS, PARTICIPANTS:
Midfacial distraction was studied as a representative craniofacial operation. A
consecutive series of 29 patients who underwent a single type of midfacial
distraction was included. INTERVENTION: For a subset of patients, computed
tomography-derived 3D models were used to study patient-specific anatomy and
precontour hardware. MAIN OUTCOME MEASURES: Complications, operative time, blood
loss, and estimated cost. RESULTS: Twenty patients underwent midfacial
distraction without and nine with preoperative use of a 3D model. Seven
complications occurred in six patients without model use, including premature
consolidation (3), cerebrospinal fluid leak (2), and hardware malfunction (2). No
complications were reported in the model group. Controlling for surgeon
variation, model use resulted in a 31.3-minute (7.8%) reduction in operative
time. Time-based cost savings were estimated to be $1036. CONCLUSIONS: Three
dimensional models are valuable for preoperative planning and hardware
precontouring in craniofacial surgery, with potential positive effects on
complications and operative time. Savings related to operative time and
complications may offset much of the cost of the model.
PMID- 27486912
TI - The Proteasome: More Than a Means to an End.
AB - The proteasome regulates timed degradation of proteins using both intrinsic and
extrinsic receptors that recognize polyubiquitin chains on targets. In this issue
of Structure, Chen et al. (2016) outline the structural basis of how intrinsic
receptors prefer ubiquitin-like domains rather than ubiquitin, to bind extrinsic
co-receptors.
PMID- 27486911
TI - Glycogen synthase kinase-3beta is a pivotal mediator of cancer invasion and
resistance to therapy.
AB - Tumor cell invasion and resistance to therapy are the most intractable biological
characteristics of cancer and, therefore, the most challenging for current cancer
research and treatment paradigms. Refractory cancers, including pancreatic cancer
and glioblastoma, show an inextricable association between the highly invasive
behavior of tumor cells and their resistance to chemotherapy, radiotherapy and
targeted therapies. These aggressive properties of cancer share distinct cellular
pathways that are connected to each other by several molecular hubs. There is
increasing evidence to show that glycogen synthase kinase (GSK)-3beta is
aberrantly activated in various cancer types and this has emerged as a potential
therapeutic target. In many but not all cancer types, aberrant GSK3beta sustains
the survival, immortalization, proliferation and invasion of tumor cells, while
also rendering them insensitive or resistant to chemotherapeutic agents and
radiation. Here we review studies that describe associations between therapeutic
stimuli/resistance and the induction of pro-invasive phenotypes in various cancer
types. Such cancers are largely responsive to treatment that targets GSK3beta.
This review focuses on the role of GSK3beta as a molecular hub that connects
pathways responsible for tumor invasion and resistance to therapy, thus
highlighting its potential as a major cancer therapeutic target. We also discuss
the putative involvement of GSK3beta in determining tumor cell stemness that
underpins both tumor invasion and therapy resistance, leading to intractable and
refractory cancer with dismal patient outcomes.
PMID- 27486913
TI - Forcing FAK into Transcriptional Activity.
AB - Focal adhesion kinase (FAK) has known signaling roles in cytoplasmic adhesion
structures, but was recently shown to act as a transcriptional regulator in the
nucleus. In this issue of Structure, Cardoso et al. (2016) report that mechanical
forces translocate FAK to the nucleus of cardiomyocytes, and provide structural
insights into how FAK interacts with the MEF2 transcription factor to control
cardiac hypertrophy.
PMID- 27486914
TI - Drug Discovery Gets a Boost from Data Science.
AB - In this issue of Structure, Schiebel et al. (2016) describe a workflow-driven
approach to high-throughput X-ray crystallographic fragment screening and
refinement. In doing so, they extend the applicability of X-ray crystallography
as a primary fragment-screening tool and show how data science techniques can
favorably impact drug discovery efforts.
PMID- 27486915
TI - Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide
Reductase with Double ATP Cones.
PMID- 27486916
TI - Job stress dimension and work-related musculoskeletal disorders among southeast
Nigerian physiotherapists.
AB - BACKGROUND: Although publications describe physical demands of the job in the
physiotherapy profession, there is a dearth of literature on job stress
dimensions (JSDs), and their relationship to work-related musculoskeletal
disorders (WMSDs). OBJECTIVE: To investigate JSDs and their relationship to WMSDs
among physiotherapists currently practicing in southeast Nigeria. METHOD: A cross
sectional study using items related to the Job Content Questionnaire and the
Nordic musculoskeletal questionnaire. Data were summarized with descriptive
statistics, and the relationship between WMSDs and JSDs was analyzed with the
Mann-Whitney U test. RESULTS: A total of 126 physiotherapists responded. There
were high levels of stress in most of the job dimensions investigated: 82.1% and
22.8% of the physiotherapists had WMSDs in at least one body region in the last
12 months and the last 7 days respectively. The lower back was the most commonly
affected in both periods. No specific domain was related to development of WMSDs.
CONCLUSION: Over 80% of physiotherapists in southeast Nigeria have WMSDs.
However, despite high levels of physical demands on the job, physiotherapists
have job control and good social support. Intervention programs aimed at reducing
WMSDs in physiotherapists should focus on risk factors that target the physical
demands of the job.
PMID- 27486917
TI - Growth of single-layer boron nitride dome-shaped nanostructures catalysed by iron
clusters.
AB - We report on the growth and formation of single-layer boron nitride dome-shaped
nanostructures mediated by small iron clusters located on flakes of hexagonal
boron nitride. The nanostructures were synthesized in situ at high temperature
inside a transmission electron microscope while the e-beam was blanked. The
formation process, typically originating at defective step-edges on the boron
nitride support, was investigated using a combination of transmission electron
microscopy, electron energy loss spectroscopy and computational modelling.
Computational modelling showed that the domes exhibit a nanotube-like structure
with flat circular caps and that their stability was comparable to that of a
single boron nitride layer.
PMID- 27486918
TI - Prediction of whelping date in large and giant canine breeds by ultrasonography
foetal biometry.
AB - OBJECTIVES: To derive the growth curves of the inner chorionic cavity and the
biparietal diameter in large and giant dog breeds by ultrasonographic foetal
biometry. To evaluate their accuracy in the prediction of whelping date and the
effect of litter size and foetal sex ratio. METHODS: Foetal biometry parameters
were obtained using serial ultrasonographic examinations in eight large (26 to 40
kg) and nine giant (>40 kg) pregnant bitches with known breeding dates and
concentrations of serum progesterone during oestrus. The relationship between
inner chorionic cavity or biparietal diameter growth and days to parturition were
analysed by linear regression and the equations derived from the growth curves
were applied to predict the whelping day. The accuracy of the prediction
(whelping day +/-1 day and +/-2 days) and the litter size and sex ratio were
recorded. RESULTS: The results showed a significant relationship between days
before parturition and inner chorionic cavity or biparietal diameter. The overall
accuracy at +/-2 days was greater, than that at +/-1 day. In giant breed bitches,
the accuracy of the prediction by biparietal diameter was significantly lower in
small, than normal litter size. No effect of foetal sex ratio was observed.
CLINICAL SIGNIFICANCE: Foetal biometry parameters obtained by ultrasonography can
be used to predict whelping dates in large and giant dog breeds.
PMID- 27486919
TI - Hypothetical orchestrated cooperation between dopaminergic and kinin receptors
for the regulation of common functions.
AB - The G protein-coupled receptors (GPCRs), one of the largest protein families, are
essential components of the most commonly used signal-transduction systems in
cells. These receptors, often using common pathways, may cooperate in the
regulation of signal transmission to the cell nucleus. Recent scientific
interests increasingly focus on the cooperation between these receptors,
particularly in a context of their oligomerization, e.g. the formation of dimers
that are able to change characteristic signaling of each receptor. Numerous
studies on kinin and dopamine receptors which belong to this family of receptors
have shown new facts demonstrating their direct interactions with other GPCRs. In
this review, current knowledge on signaling pathways and oligomerization of these
receptors has been summarized. Owing to the fact that kinin and dopamine
receptors are widely expressed in cell membranes where they act as mediators of
numerous common physiological processes, the information presented here sheds new
light on a putative crosstalk of these receptors and provides more comprehensive
understanding of possible direct interactions that may change their functions.
The determination of such interactions may be useful for the development of new
targeted therapeutic strategies against many disorders in which kinin and
dopamine receptors are involved.
PMID- 27486920
TI - Column chromatography as a useful step in purification of diatom pigments.
AB - Fucoxanthin, diadinoxanthin and diatoxanthin are carotenoids found in brown algae
and most other heterokonts. These pigments are involved in photosynthetic and
photoprotective reactions, and they have many potential health benefits. They can
be extracted from diatom Phaeodactylum tricornutum by sonication, extraction with
chloroform : methanol and preparative thin layer chromatography. We assessed the
utility of an additional column chromatography step in purification of these
pigments. This novel addition to the isolation protocol increased the purity of
fucoxanthin and allowed for concentration of diadinoxanthin and diatoxanthin
before HPLC separation. The enhanced protocol is useful for obtaining high purity
pigments for biochemical studies.
PMID- 27486921
TI - Abscisic acid and blue light signaling pathways in chloroplast movements in
Arabidopsis mesophyll.
AB - Abscisic acid (ABA) and phototropins act antagonistically to control stomatal
movements. Here, we investigated the role of ABA in phototropin-directed
chloroplast movements in mesophyll cells of Arabidopsis thaliana. We analyzed the
expression of phototropins at mRNA and protein level under the influence of ABA.
PHOT1 mRNA level was decreased by ABA in the dark while it was insensitive to ABA
in light. PHOT2 mRNA level was independent of the hormone treatment. The levels
of phototropin proteins were down-regulated by ABA, both in darkness and light.
No impact of exogenous ABA on amplitudes and kinetics of chloroplast movements
was detected. Chloroplast responses in wild type Arabidopsis and three mutants,
abi4, abi2 (abscisic acid insensitive4, 2) and aba1 (abscisic acid1), were
measured to account for endogenous ABA signaling. The chloroplast responses were
slightly reduced in abi2 and aba1 mutants in strong light. To further investigate
the effect, abi2 and aba1 mutants were supplemented with exogenous ABA. In the
aba1 mutant, the reaction was rescued but in abi2 it was unaffected. Our results
show that ABA is not directly involved in phototropin-controlled chloroplast
responses in mature leaves of Arabidopsis. However, the disturbance of ABA
biosynthesis and signaling in mutants affects some elements of the chloroplast
movement mechanism. In line with its role as a stress hormone, ABA appears to
enhance plant sensitivity to light and promote the chloroplast avoidance
response.
PMID- 27486922
TI - Prison officers' views about hepatitis C testing and treatment: a qualitative
enquiry.
AB - AIMS AND OBJECTIVES: To explore the views of prison officers in an English
category B male prison about people in prison being tested and treated for
hepatitis C. BACKGROUND: Hepatitis C testing and treatment in English prisons
remain low with the reasons being poorly understood. Prison officers are in
continuous contact with prisoners so might observe factors that may influence
people in prisons' choice in whether to accept hepatitis C testing and treatment.
DESIGN: A qualitative design within an interpretative framework was employed.
METHODS: Semistructured interviews were conducted with 10 prison officers at an
English male category B prison. The interviews were audiorecorded and transcribed
at the prison. RESULTS: Four themes emerged Safeguarding, Stigma, Confidentiality
and Education. Hepatitis C testing and treatment were supported in principle but
if a person in prison poses a threat to the overall security of a prison, any
health issues that are not immediately life threatening will be overridden,
irrespective of the financial or health consequences. The prison officers
respected people in prisons' confidentiality regarding health matters, but this
could be compromised during violent incidents. All of the prison officers
displayed limited knowledge about hepatitis C. CONCLUSIONS: This qualitative
enquiry illustrates that prison security transcends health. This suggests that
health providers may need to offer greater flexibility and collaboration across
the network of National Health Service hospitals to maintain continuity in
treatment if a prisoner is moved to a different establishment or liberated.
RELEVANCE TO CLINICAL PRACTICE: This study introduces the notion that prison
security staff may have a potential role in promoting or discouraging hepatitis C
testing and treatment by the ways in which their knowledge impacts on their
interactions with people in prison. Engaging this staff group in educational
opportunities should be a component of commissioned hepatitis service delivery in
prisons.
PMID- 27486923
TI - Piezophototronic Effect in Single-Atomic-Layer MoS2 for Strain-Gated Flexible
Optoelectronics.
AB - Strain-gated flexible optoelectronics are reported based on monolayer MoS2 .
Utilizing the piezoelectric polarization created at the metal-MoS2 interface to
modulate the separation/transport of photogenerated carriers, the
piezophototronic effect is applied to implement atomic-layer-thick
phototransistor. Coupling between piezoelectricity and photogenerated carriers
may enable the development of novel optoelectronics.
PMID- 27486924
TI - Molecular self-assembly using peptide nucleic acids.
AB - Peptide nucleic acids (PNAs) are extensively studied for the control of genetic
expression since their design in the 1990s. However, the application of PNAs in
nanotechnology is much more recent. PNAs share the specific base-pair recognition
characteristic of DNA together with material-like properties of polyamides, both
proteins and synthetic polymers, such as Kevlar and Nylon. The first application
of PNA was in the form of PNA-amphiphiles, resulting in the formation of either
lipid integrated structures, hydrogels or fibrillary assemblies. Heteroduplex DNA
PNA assemblies allow the formation of hybrid structures with higher stability as
compared with pure DNA. A systematic screen for minimal PNA building blocks
resulted in the identification of guanine-containing di-PNA assemblies and
protected guanine-PNA monomer spheres showing unique optical properties. Finally,
the co-assembly of PNA with thymine-like three-faced cyanuric acid allowed the
assembly of poly-adenine PNA into fibers. In summary, we believe that PNAs
represent a new and important family of building blocks which converges the
advantages of both DNA- and peptide-nanotechnologies.
PMID- 27465247
TI - Exenatide Alters Gene Expression of Neural Cell Adhesion Molecule (NCAM),
Intercellular Cell Adhesion Molecule (ICAM), and Vascular Cell Adhesion Molecule
(VCAM) in the Hippocampus of Type 2 Diabetic Model Mice.
AB - BACKGROUND Glucagon-like peptide-1 (GLP-1), a potent and selective agonist for
the GLP-1 receptor, ameliorates the symptoms of diabetes through stimulation of
insulin secretion. Exenatide is a potent and selective agonist for the GLP-1
receptor. Cell adhesion molecules are members of the immunoglobulin superfamily
and are involved in synaptic rearrangements in the mature brain. MATERIAL AND
METHODS The present study demonstrated the effects of exenatide treatment (0.1
ug/kg, subcutaneously, twice daily for 2 weeks) on the gene expression levels of
cell adhesion molecules, neural cell adhesion molecule (NCAM), intercellular cell
adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) in the brain
tissue of diabetic BALB/c male mice by real-time quantitative polymerase chain
reaction (PCR). Diabetes was induced by streptozotocin/nicotinamide (STZ-NA)
injection to male mice. RESULTS The results of this study revealed that
hippocampal gene expression of NCAM, ICAM, and VCAM were found to be up-regulated
in STZ-NA-induced diabetic mice compared to those of controls. A significant
decrease in the gene expression levels of NCAM, ICAM, and VCAM were determined
after 2 weeks of exenatide administration. CONCLUSIONS Cell adhesion molecules
may be involved in the molecular mechanism of diabetes. Exenatide has a strong
beneficial action in managing diabetes induced by STZ/NA by altering gene
expression of NCAM, ICAM, and VCAM.
PMID- 27486926
TI - Directive and non-directive food-related parenting practices: Associations
between an expanded conceptualization of food-related parenting practices and
child dietary intake and weight outcomes.
AB - : This study examines associations between an expanded conceptualization of food
related parenting practices, specifically, directive and non-directive control,
and child weight (BMI z-score) and dietary outcomes [Healthy Eating Index (HEI)
2010, daily servings fruits/vegetables] within a sample of parent-child dyads (8
12 years old; n = 160). Baseline data from the Healthy Home Offerings via the
Mealtime Environment (HOME Plus) randomized controlled trial was used to test
associations between directive and non-directive control and child dietary
outcomes and weight using multiple regression analyses adjusted for parental
education. Overall variance explained by directive and non-directive control
constructs was also calculated. Markers of directive control included pressure-to
eat and food restriction, assessed using subscales from the Child Feeding
Questionnaire; markers of non-directive control were assessed with a parental
role modeling scale and a home food availability inventory in which an obesogenic
home food environment score was assigned based on the types and number of
unhealthful foods available within the child's home food environment. DIRECTIVE
CONTROL: Food restriction and pressure-to-eat were positively and negatively
associated with BMI z-scores, respectively, but not with dietary outcomes. NON
DIRECTIVE CONTROL: An obesogenic home food environment was inversely associated
with both dietary outcomes; parental role modeling of healthful eating was
positively associated with both dietary outcomes. Neither non-directive
behavioral construct was significantly associated with BMI z-scores. TOTAL
VARIANCE: Greater total variance in BMI-z was explained by directive control;
greater total variance in dietary outcomes was explained by non-directive
control. Including a construct of food-related parenting practices with separate
markers for directive and non-directive control should be considered for future
research. These concepts address different forms of parental control and, in the
present study, yielded unique associations with child dietary and weight
outcomes.
PMID- 27486928
TI - Biodegradation Kinetics of 1,4-Dioxane in Chlorinated Solvent Mixtures.
AB - This study investigated the impacts of individual chlorinated solvents and their
mixtures on aerobic 1,4-dioxane biodegradation by Pseudonocardia dioxanivorans
CB1190. The established association of these co-occurring compounds suggests
important considerations for their respective biodegradation processes. Our
kinetics and mechanistic studies demonstrated that individual solvents inhibited
biodegradation of 1,4-dioxane in the following order: 1,1-dichloroethene (1,1
DCE) > cis-1,2-diochloroethene (cDCE) > trichloroethene (TCE) > 1,1,1
trichloroethane (TCA). The presence of 5 mg L(-1) 1,1-DCE completely inhibited
1,4-dioxane biodegradation. Subsequently, we determined that 1,1-DCE was the
strongest inhibitor of 1,4-dioxane biodegradation by bacterial pure cultures
exposed to chlorinated solvent mixtures as well as in environmental samples
collected from a site contaminated with chlorinated solvents and 1,4-dioxane.
Inhibition of 1,4-dioxane biodegradation rates by chlorinated solvents was
attributed to delayed ATP production and down-regulation of both 1,4-dioxane
monooxygenase (dxmB) and aldehyde dehydrogenase (aldH) genes. Moreover,
increasing concentrations of 1,1-DCE and cis-1,2-DCE to 50 mg L(-1) respectively
increased 5.0-fold and 3.5-fold the expression of the uspA gene encoding a
universal stress protein. In situ natural attenuation or enhanced biodegradation
of 1,4-dioxane is being considered for contaminated groundwater and industrial
wastewater, so these results will have implications for selecting 1,4-dioxane
bioremediation strategies at sites where chlorinated solvents are present as co
contaminants.
PMID- 27486927
TI - Driving Structure-Based Drug Discovery through Cosolvent Molecular Dynamics.
AB - Identifying binding hotspots on protein surfaces is of prime interest in
structure-based drug discovery, either to assess the tractability of pursuing a
protein target or to drive improved potency of lead compounds. Computational
approaches to detect such regions have traditionally relied on energy
minimization of probe molecules onto static protein conformations in the absence
of the natural aqueous environment. Advances in high performance computing now
allow us to assess hotspots using molecular dynamics (MD) simulations. MD
simulations integrate protein flexibility and the complicated role of water,
thereby providing a more realistic assessment of the complex kinetics and
thermodynamics at play. In this review, we describe the evolution of various
cosolvent-based MD techniques and highlight a myriad of potential applications
for such technologies in computational drug development.
PMID- 27486929
TI - Towards sustainable and safe apparel cleaning methods: A review.
AB - Perchloroethylene (PERC) is a compound commonly used as a solvent in dry
cleaning, despite its severe health and environmental impacts. In recent times
chemicals such as hydrocarbons, GreenEarth((r)), acetal and liquid carbon dioxide
have emerged as less damaging substitutes for PERC, and an even more sustainable
water-based wet cleaning process has been developed. We employed a systematic
review approach to provide a comprehensive overview of the existing research
evidence in the area of sustainable and safe apparel cleaning methods and care.
Our review describes traditional professional dry cleaning methods, as well as
those that utilise solvents other than PERC, and their ecological attributes. In
addition, the new professional wet cleaning process is discussed. Finally, we
address the health hazards of the various solvents used in dry cleaning and state
of-the-art solvent residue trace analysis techniques.
PMID- 27486930
TI - Biosorption and biodegradation of a sulfur dye in high-strength dyeing wastewater
by Acidithiobacillus thiooxidans.
AB - The ability of the bacterial strain Acidithiobacillus thiooxidans to remove
sulfur blue 15 (SB15) dye from water samples was examined. This bacterium could
not only oxidize sulfur compounds to sulfuric acid but also promote the
attachment of the cells to the surface of sulfidic particles, therefore serving
as an efficient biosorbent. The biosorption isotherms were better described by
the Langmuir equation than by the Freundlich or Dubinin-Radushkevich equation.
Also, the biosorption process followed the pseudo-second-order kinetics. At pH
8.3 and SB15 concentrations up to 2000 mg L(-1) in the biomass/mineral salt
solution, the dye removal and decolorization were 87.5% and 91.4%, respectively,
following the biosorption process. Biodegradation was proposed as a subsequent
process for the remaining dye (250-350 mg L(-1)). A central composite design was
used to analyze independent variables in the response surface methodology study.
Under the optimal conditions (i.e., initial dye concentration of 300 mg L(-1),
initial biomass concentration of 1.0 g L(-1), initial pH of 11.7, and yeast
extract dose of 60 mg L(-1)), up to 50% of SB15 was removed after 4 days of
biodegradation.
PMID- 27486931
TI - Taxonomy and Phylogeny of Polyporus Group Melanopus (Polyporales, Basidiomycota)
from China.
AB - Melanopus is a morphological group of Polyporus which contains species with a
black cuticle on the stipe. In this article, taxonomic and phylogenetic studies
on Melanopus group were carried out on the basis of morphological characters and
phylogenetic evidence of DNA sequences of multiple loci including the internal
transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene
(nLSU), the small subunit nuclear ribosomal RNA gene (nSSU), the small subunit
mitochondrial rRNA gene sequences (mtSSU), the translation elongation factor 1
alpha gene (EF1-alpha), the largest subunit of RNA polymerase II (RPB1), the
second largest subunit of RNA polymerase II (RPB2), and beta-tubulin gene
sequences (beta-tubulin). The phylogenetic result confirmed that the previously
so-called Melanopus group is not a monophyletic assemblage, and species in this
group distribute into two distinct clades: the Picipes clade and the Squamosus
clade. Four new species of Picipes are described, and nine new combinations are
proposed. A key to species of Picipes is provided.
PMID- 27486932
TI - VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of
Diabetic Macular Edema.
AB - Diabetic macular edema (DME), characterized by an increase of thickness in the
eye macular area, is due to breakdown of the blood-retinal barrier (BRB). Hypoxia
plays a key role in the progression of this pathology by activating the hypoxia
inducible factors. In the last years, various studies have put their attention on
the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and
vasoactive intestinal peptide (VIP) in retinal dysfunction. However, until now,
no study has investigated their protective role against the harmful combined
effect of both hyperglycemia and hypoxia on outer BRB. Therefore, in the present
study, we have analyzed the role of these peptides on permeability, restoration
of tight junctions expression and inhibition of hyperglycemia/hypoxia-induced
apoptosis, in an experimental in vitro model of outer BRB. Our results have
demonstrated that the peptides' treatment have restored the integrity of outer
BRB induced by cell exposure to hyperglycemia/hypoxia. Their effect is mediated
through the activation of phosphoinositide 3 kinase (PI3K)/Akt and mammalian
mitogen activated protein kinase/Erk kinase (MAPK/ERK) signaling pathways. In
conclusion, our study further clarifies the mechanism through which PACAP and VIP
perform the beneficial effect on retinal damage induced by hyperglycemic/hypoxic
insult, responsible of DME progression. J. Cell. Physiol. 232: 1079-1085, 2017.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27486933
TI - Asymmetric and Upper Body Parkinsonism in Patients with Idiopathic Normal
Pressure Hydrocephalus.
AB - BACKGROUND AND PURPOSE: Our aims were to analyze the characteristics of
parkinsonian features and to characterize changes in parkinsonian motor symptoms
before and after the cerebrospinal fluid tap test (CSFTT) in idiopathic normal
pressure hydrocephalus (INPH) patients. METHODS: INPH subjects were selected in
consecutive order from a prospectively enrolled INPH registry. Fifty-five INPH
patients (37 males) having a positive response to the CSFTT constituted the final
sample for analysis. The mean age was 73.7+/-4.7 years. The pre-tap mean Unified
Parkinson's Disease Rating Scale motor (UPDRS-III) score was 24.5+/-10.2.
RESULTS: There was no significant difference between the upper and lower body
UPDRS-III scores (p=0.174). The parkinsonian signs were asymmetrical in 32 of 55
patients (58.2%). At baseline, the Timed Up and Go Test and 10-meter walking test
scores were positively correlated with the total motor score, global bradykinesia
score, global rigidity score, upper body score, lower body score, and postural
instability/gait difficulties score of UPDRS-III. After the CSFTT, the total
motor score, global bradykinesia score, upper body score, and lower body score of
UPDRS-III significantly improved (p<0.01). There was a significant decrease in
the number of patients with asymmetric parkinsonism (p<0.05). CONCLUSIONS: In the
differential diagnosis of elderly patients presenting with asymmetric and upper
body parkinsonism, we need to consider a diagnosis of INPH. The association
between gait function and parkinsonism severity suggests the involvement of
similar circuits producing gait and parkinsonian symptoms in INPH.
PMID- 27486934
TI - Clinical Considerations of Obstructive Sleep Apnea with Little REM Sleep.
AB - BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is more severe during rapid
eye movement (REM) sleep than during non-REM sleep. We aimed to determine the
features of patients with OSA who experience little REM sleep. METHODS: Patients
with a chief complaint of sleep-disordered breathing were enrolled. All subjects
underwent overnight polysomnography (PSG) and completed questionnaires on sleep
quality. Patients were divided into the following three groups according to the
proportion of REM sleep detected in overnight PSG: little REM sleep [REM sleep
<20% of total sleep time (TST)], normal REM sleep (20-25% of TST), and excessive
REM sleep (>25% of TST). Multiple logistic regression analyses were applied to
the data. The success rate of continuous positive airway pressure (CPAP)
titration was estimated in these groups. RESULTS: The age and body mass index of
the patients were 47.9+/-15.9 years (mean+/-SD) and 25.2+/-4.1 kg/m2,
respectively. The 902 patients comprised 684 (76%) men and 218 (24%) women. The
apnea-hypopnea index (AHI) in the little-REM-sleep group was 22.1+/-24.4
events/hour, which was significantly higher than those in the other two groups
(p<0.05). Multiple logistic regression showed that a higher AHI (p<0.001; odds
ratio, 1.512; 95% confidence interval, 1.020-1.812) was independently predictive
of little REM sleep. The titration success rate was lower in the little-REM-sleep
group than in the normal-REM-sleep group (p=0.038). CONCLUSIONS: The AHI is
higher and the success rate of CPAP titration is lower in OSA patients with
little REM sleep than those with normal REM sleep.
PMID- 27486935
TI - Detection of Listeria monocytogenes in CSF from Three Patients with
Meningoencephalitis by Next-Generation Sequencing.
AB - BACKGROUND AND PURPOSE: Encephalitis caused by Listeria monocytogenes (L.
monocytogenes) is rare but sometimes fatal. Early diagnosis is difficult using
routine cerebrospinal fluid (CSF) tests, while next-generation sequencing (NGS)
is increasingly being used for the detection and characterization of pathogens.
METHODS: This study set up and applied unbiased NGS to detect L. monocytogenes in
CSF collected from three cases of clinically suspected listeria
meningoencephalitis. RESULTS: Three cases of patients with acute/subacute
meningoencephalitis are reported. Magnetic resonance imaging and blood cultures
led to a suspected diagnosis of L. monocytogenes, while the CSF cultures were
negative. Unbiased NGS of CSF identified and sequenced reads corresponding to L.
monocytogenes in all three cases. CONCLUSIONS: This is the first report
highlighting the feasibility of applying NGS of CSF as a diagnostic method for
central nervous system (CNS) L. monocytogenes infection. Routine application of
this technology in clinical microbiology will significantly improve diagnostic
methods for CNS infectious diseases.
PMID- 27486936
TI - Projected Numbers of Ischemic Strokes Recorded in the Austrian Stroke-Unit
Registry from 2012 to 2075.
AB - BACKGROUND AND PURPOSE: This study analyzed the number of patients with ischemic
strokes recorded in the Austrian Stroke-Unit Registry with the aim of projecting
this number from 2012 to 2075 and to highlight that the Austrian health system
will face a dramatic increase in older patients within the next few decades.
METHODS: Current demographic information was obtained from EUROSTAT, and
information on age- and sex-stratified 1-year incidence rates of ischemic stroke
were obtained from the Austrian Stroke-Unit Registry. Sensitivity analysis was
performed by analyzing the projections based on predicted ageing, main, and
growth population scenarios, and with stratification by age and gender. RESULTS:
The total number of ischemic strokes recorded in the Austrian Stroke-Unit
Registry was 8,690 in 2012 and is expected to increase to 15,826, 15,626, or
18,134 in 2075 according to the ageing, main, and growth scenarios, respectively.
The corresponding numbers of patients are projected to increase or decrease
within different age strata as follows (100%=number of registered ischemic
strokes in 2012): 0-40 years, 100%/99% (males/females); 40-50 years, 83%/83%; 50
60 years, 98%/97%; 60-70 years, 126%/119%; 70-80 years, 159%/139%; 80-90 years,
307%/199%; and 90+ years, 894%/413%. CONCLUSIONS: The ageing population in
Austria will result in the number of patients increasing considerably from 2012
to 2075, to 182%, 180%, or 208% (relative to 100% in 2012) according to the
ageing, main, and growth scenarios, respectively; the corresponding value among
those aged 80+ years is 315%, 290%, or 347%. These figures demonstrated the
importance of improving primary preventive measures. The results of this study
should provide a basis for discussions among health-care professionals and
economists to face the future large financial burden of ischemic stroke on the
Austrian health system.
PMID- 27486938
TI - Optic Neuritis in a Patient with Bickerstaff's Brainstem Encephalitis.
PMID- 27486937
TI - Effects of Regular Treadmill Exercise on a DNA Oxidative-Damage Marker and Total
Antioxidant Capacity in Rat Hippocampal Tissue.
AB - BACKGROUND AND PURPOSE: Regular exercise can result in changes in the levels of
oxidative stress in the hippocampus; however, little attention has been paid to
physical-activity-induced neuronal protection to exposure to lead compounds. This
study investigated the effects of regular treadmill exercise on a DNA oxidative
damage marker [8-hydroxy-2'-deoxyguanosine (8-OHdG)] and the total antioxidant
capacity (TAC) of hippocampal tissue in lead-acetate exposed rats. METHODS: This
study investigated the effects of 8 weeks of regular treadmill exercise on 8-OHdG
and the TAC of hippocampal tissue in lead-acetate-exposed rats. Wistar rats were
randomly divided into four groups: baseline, sham (control), lead, and
exercise+lead. The exercise program involved running on a treadmill with
increasing intensity five times a week for 8 weeks. Animals in the lead and
exercise+lead groups received lead acetate at 20 mg/kg body weight
intraperitoneally three times weekly for 8 weeks. Animals in the sham group
received solvent (ethyl oleate) at 30 mg/kg body weight three times weekly for 8
weeks. TAC and 8-OHdG were measured by spectrophotometric and ELISA techniques,
respectively. Data were analyzed by ANOVA and Tukey's post-hoc test with a
significance cutoff of p<=0.05. RESULTS: The level of 8-OHdG and the TAC were
significantly higher and lower, respectively, in the lead group than in the
baseline and sham groups (p<0.01). However, the 8-OHdG level and TAC value in
hippocampal tissue were significantly decreased and increased, respectively, in
the exercise+lead group relative to the lead group (p<0.05). CONCLUSIONS: The TAC
of hippocampal tissue may be directly associated with neural protection
mechanisms of exercise following lead acetate injection, and the beneficial
effects of regular exercise in preventing hippocampal neuronal damage could be
due to decreased hippocampal oxidative stress such as reflected by a lower 8-OHdG
level and increased TAC.
PMID- 27486939
TI - Leber's 'Plus' in a Korean Patient with 14484/ND6 Mutation.
PMID- 27486940
TI - A Large Dominant Myotonia Congenita Family with a V1293I Mutation in SCN4A.
PMID- 27486944
TI - Response, Letter to the Editor.
PMID- 27486943
TI - Letter to the Editor: Sex Steroids and Vascular Calcification.
PMID- 27486945
TI - Letter to the Editor: The Value of Molecular Testing for Effective Management of
Patients With Indeterminate Thyroid Nodules.
PMID- 27486946
TI - Response to the Letter to the Editor.
PMID- 27486947
TI - Letter to the Editor: Combination Treatment With Teriparatide and Denosumab in
Osteoporosis.
PMID- 27486948
TI - An innovative approach for sequential extraction of phosphorus in sediments:
Ferrous iron P as an independent P fraction.
AB - Accurate identification of phosphorus (P) forms is crucially important for
understanding the geochemical cycle of P; however, until now the role of ferrous
iron P (Fe(II)-P) buried in sediments has been completely ignored in nearly all
sequential extraction procedures developed. Using sediment cores sampled from
Donghu Lake in Wuhan, China, this study explored a modified version of widely
used sequential P extraction method (SEDEX; Ruttenberg, 1992) in which Fe(II)-P
was identified as an independent fraction. Based on the high selectivity of the
extractant (0.2% 2,2'-bipyridine+0.1 M KCl) and the dissolution equilibrium of P,
procedures for extracting Fe(II)-P were optimized using a 1:100 solid:liquid
ratio and extraction at 50 +/- 1 degrees C for 24 h. The sedimentary P extracted
was divided into five fractions: loosely-bound P, Fe(II)-P, CDB-P, Ca-P and O-P.
Fe(II)-P was the predominant fraction in fresh sediments in Donghu Lake,
accounting for 15.7-49.9% of TP, with a mean of 31.6%. The mean values of Ca-P, O
P, CDB-P and loosely-bound P were 28.4%, 22.7%, 17.1% and 4.3%, respectively.
Combined with component analysis of extracts and recovery experiments of standard
reference minerals (vivianite, Fe3(PO4)2.8H2O) in natural sediments, extraction
of Fe(II)-P with 0.2% 2,2-bipridine and 0.1 M KCl was robust, with a good
recovery rate (88.7-100.6%) and little of the Ca-P dissolved. It is possible to
use this innovative SEDEX not only to distinguish the contribution of different P
matrices in fresh sediments, but also to investigate the transformation of
sedimentary P under different redox conditions. Therefore, greater focus on
Fe(II)-P is necessary, because it is a major sink for the geochemical process of
sedimentary P.
PMID- 27486949
TI - Microbial community adaptation influences long-chain fatty acid conversion during
anaerobic codigestion of fats, oils, and grease with municipal sludge.
AB - Codigesting fats, oils, and greases with municipal wastewater sludge can greatly
improve biomethane recovery at wastewater treatment facilities. Process loading
rates of fats, oils, and greases have been previously tested with little
knowledge of the digester microbial community structure, and high transient fat
loadings have led to long chain fatty acid (LCFA) accumulation and digester
upsets. This study utilized recently-developed quantitative PCR assays for
syntrophic LCFA-degrading bacteria along with 16S amplicon sequencing to relate
changes in microbial community structure to LCFA accumulation during transient
loading increases to an anaerobic codigester receiving waste restaurant oil and
municipal wastewater sludge. The 16S rRNA gene concentration of the syntrophic
beta-oxidizing genus Syntrophomonas increased to ~15% of the Bacteria community
in the codigester, but stayed below 3% in the control digester that was fed only
wastewater sludge. Methanosaeta and Methanospirillum were the dominant
methanogenic genera enriched in the codigester, and together comprised over 80%
of the Archaea community by the end of the experimental period. Constrained
ordination showed that changes in the codigester Bacteria and Archaea community
structures were related to measures of digester performance. Notably, the
effluent LCFA concentration in the codigester was positively correlated to the
specific loading rate of waste oil normalized to the Syntrophomonas 16S rRNA
concentration. Specific loading rates of 0-1.5 * 10(-12) g VS oil/16S gene copies
day resulted in LCFA concentrations below 30 mg/g TS, whereas LCFA accumulated up
to 104 mg/g TS at higher transient loading rates. Based on the community
dependent loading limitations found, enhanced biomethane production from high
loadings of fats, oils and greases can be achieved by promoting a higher biomass
of slow-growing syntrophic consortia, such as with longer digester solids
retention times. This work also demonstrates the potential for controlling the
loading rate of fats, oils, and greases based on the analysis of the codigester
community structure, such as with quantitative PCR measurements of syntrophic
LCFA-degrading bacteria abundance.
PMID- 27486950
TI - Simultaneous bioremediation and biodetection of mercury ion through surface
display of carboxylesterase E2 from Pseudomonas aeruginosa PA1.
AB - Mercury is a toxic heavy metal and presents significant threats to organisms and
natural ecosystems. Recently, the mercury remediation as well as its detection by
environmental-friendly biotechnology has received increasing attention. In this
study, carboxylesterase E2 from mercury-resistant strain Pseudomonas aeruginosa
PA1 has been successfully displayed on the outer membrane of Escherichia coli
Top10 bacteria to simultaneously adsorb and detect mercury ion (Hg(2+)). The
transmission electron microscopy analysis shows that Hg(2+) can be absorbed by
carboxylesterase E2 and accumulated on the outer membrane of surface-displayed E.
coli bacteria. The adsorption of Hg(2+) followed a physicochemical, equilibrated
and saturatable mechanism, which well fits the traditional Langmuir adsorption
model. The surface-displayed system can be regenerated through regulating pH
values. As its activity can be inhibited by Hg(2+), carboxylesterase E2 has been
used to detect the concentration of Hg(2+) in water samples. The developed
surface display system will be of great potential in the simultaneous
bioremediation and biodetection of environmental mercury pollution.
PMID- 27486951
TI - Impact of algal organic matter released from Microcystis aeruginosa and Chlorella
sp. on the fouling of a ceramic microfiltration membrane.
AB - Algal blooms lead to the secretion of algal organic matter (AOM) from different
algal species into water treatment systems, and there is very limited information
regarding the impact of AOM from different species on the fouling of ceramic
microfiltration (MF) membranes. The impact of soluble AOM released from
Microcystis aeruginosa and Chlorella sp. separately and together in feedwater on
the fouling of a tubular ceramic microfiltration membrane (alumina, 0.1 MUm) was
studied at lab scale. Multi-cycle MF tests operated in constant pressure mode
showed that the AOM (3 mg DOC L(-1)) extracted from the cultures of the two algae
in early log phase of growth (12 days) resulted in less flux decline compared
with the AOM from stationary phase (35 days), due to the latter containing
significantly greater amounts of high fouling potential components (protein and
humic-like substances). The AOM released from Chlorella sp. at stationary phase
led to considerably greater flux decline and irreversible fouling resistance
compared with that from M. aeruginosa. The mixture of the AOM (1:1, 3 mg DOC L(
1)) from the two algal species showed more similar flux decline and irreversible
fouling resistance to the AOM from M. aeruginosa than Chlorella sp. This was due
to the characteristics of the AOM mixture being more similar to those for M.
aeruginosa than Chlorella sp. The extent of the flux decline for the AOM mixture
after conventional coagulation with aluminium chlorohydrate or alum was reduced
by 70%.
PMID- 27486952
TI - European longitudinal study on the relationship between adolescents' alcohol
marketing exposure and alcohol use.
AB - BACKGROUND AND AIMS: This is the first study to examine the effect of alcohol
marketing exposure on adolescents' drinking in a cross-national context. The aim
was to examine reciprocal processes between exposure to a wide range of alcohol
marketing types and adolescent drinking, controlled for non-alcohol branded media
exposure. DESIGN: Prospective observational study (11-12- and 14-17-month
intervals), using a three-wave autoregressive cross-lagged model. SETTING: School
based sample in 181 state-funded schools in Germany, Italy, Netherlands, Poland.
PARTICIPANTS: A total of 9075 eligible respondents participated in the survey
(mean age 14 years, 49.5% male. MEASUREMENTS: Adolescents reported their
frequency of past-month drinking and binge drinking. Alcohol marketing exposure
was measured by a latent variable with 13 items measuring exposure to online
alcohol marketing, televised alcohol advertising, alcohol sport sponsorship,
music event/festival sponsorship, ownership alcohol-branded promotional items,
reception of free samples and exposure to price offers. Confounders were age,
gender, education, country, internet use, exposure to non-alcohol sponsored
football championships and television programmes without alcohol commercials.
FINDINGS: The analyses showed one-directional long-term effects of alcohol
marketing exposure on drinking (exposure T1 on drinking T2: beta = 0.420 (0.058),
P < 0.001, 95% confidence interval (CI) = 0.324-0.515; exposure T2 on drinking
T3: beta = 0.200 (0.044), P < 0.001, 95% CI = 0.127-0.272; drinking T1 and
drinking T2 on exposure: P > 0.05). Similar results were found in the binge
drinking model (exposure T1 on binge T2: beta = 0.409 (0.054), P < 0.001, 95% CI
= 0.320-0.499; exposure T2 on binge T3: beta = 0.168 (0.050), P = 0.001, 95% CI =
0.086-0.250; binge T1 and binge T2 on exposure: P > 0.05). CONCLUSIONS: There
appears to be a one-way effect of alcohol marketing exposure on adolescents'
alcohol use over time, which cannot be explained by either previous drinking or
exposure to non-alcohol-branded marketing.
PMID- 27486953
TI - Comparison of semiologies between tilt-induced psychogenic nonsyncopal collapse
and psychogenic nonepileptic seizures.
AB - We sought to characterize the clinical features of tilt-induced psychogenic
nonsyncopal collapse (PNSC) from a cohort of young patients and to compare the
semiologies between PNSC and EEG-confirmed psychogenic nonepileptic seizures
(PNES). A PNSC diagnosis was made if a clinical event occurred during tilt-table
testing that the patient regarded as fainting, but neither hypotension nor EEG
changes were present. A diagnosis of PNSC was made in 17.6% of all patients
referred during the 15-month study period. Cohorts with psychogenic nonsyncopal
collapse (n=40) and PNES (n=40) did not differ in age (15.5+/-2.2 versus 14.6+/
2.7, p=.11) or female gender (80% versus 72.5%, p=.43). Psychogenic nonsyncopal
collapse events were briefer than PNES events (median: 45 versus 201.5s, p<.001).
Negative motor signs (head drop, body limpness) predominated in PNSC (85% versus
20%, p<.001), while the positive motor signs of convulsion occurred more often
with PNES (90% versus 30%, p<.001). Behavioral arrest (25% versus 32.5%, p=.46)
and eye closure (85% versus 72.5%, p=.21) did not differ between PNSC and PNES.
Patients with PNSC were more likely to be tearful before (30% versus 7.5%, p=.02)
and after (62.5% versus 7.5%, p<.001) an event. In conclusion, although overlap
exists, the features of PNSC generally appear similar to neurally mediated
syncope, while the features of PNES generally appear similar to epileptic
seizures. Psychogenic nonsyncopal collapse and PNES likely represent similar
disorders that differ primarily by clinical semiologies and referral patterns.
PMID- 27486954
TI - Highly Conserved Testicular Localization of Claudin-11 in Normal and Impaired
Spermatogenesis.
AB - In this study we tested expression of tight junction proteins in human, mouse and
rat and analyzed the localization of claudin-11 in testis of patients with normal
and impaired spermatogenesis. Recent concepts generated in mice suggest that the
stage-specifically expressed claudin-3 acts as a basal barrier, sealing the
seminiferous epithelium during migration of spermatocytes. Corresponding
mechanisms have never been demonstrated in humans. Testicular biopsies (n = 103)
from five distinct groups were analyzed: normal spermatogenesis (NSP, n = 28),
hypospermatogenesis (Hyp, n = 24), maturation arrest at the level of primary
spermatocytes (MA, n = 24), Sertoli cell only syndrome (SCO, n = 19), and
spermatogonial arrest (SGA, n = 8). Protein expression of claudin-3, -11 and
occludin was analyzed. Human, mice and rat testis robustly express claudin-11
protein. Occludin was detected in mouse and rat and claudin-3 was found only in
mice. Thus, we selected claudin-11 for further analysis of localization. In NSP,
claudin-11 is located at Sertoli-Sertoli junctions and in Sertoli cell contacts
towards spermatogonia. Typically, claudin-11 patches do not reach the basal
membrane, unless flanked by the Sertoli cell body or patches between two Sertoli
cell bodies. The amount of basal claudin-11 patches was found to be increased in
impaired spermatogenesis. Only claudin-11 is expressed in all three species
examined. The claudin-11 pattern is robust in man with impaired spermatogenesis,
but the proportion of localization is altered in SCO and MA. We conclude that
claudin-11 might represent the essential component of the BTB in human.
PMID- 27486955
TI - A wearable, highly stable, strain and bending sensor based on high aspect ratio
graphite nanobelts.
AB - A simple and scalable method was developed for the fabrication of wearable strain
and bending sensors, based on high aspect ratio (length/thickness ~10(3))
graphite nanobelt thin films deposited by a modified Langmuir-Blodgett technique
onto flexible polymer substrates. The sensing mechanism is based on the changes
in contact resistance between individual nanobelts upon substrate deformation.
Very high sensor response stability for more than 5000 strain-release cycles and
a device power consumption as low as 1 nW were achieved. The device maximum
stretchability is limited by the metal electrodes and the polymer substrate; the
maximum strain that could be applied to the polymer used in this work was 40%.
Bending tests carried out for various radii of curvature demonstrated distinct
sensor responses for positive and negative curvatures. The graphite nanobelt thin
flexible films were successfully tested for acoustic vibration and heartbeat
sensing.
PMID- 27486956
TI - Optimal dehydrothermal processing conditions to improve biocompatibility and
durability of a weakly denatured collagen scaffold.
AB - Collagen scaffolds are essential for tissue regeneration; however, preprocessing
of these scaffolds is necessary because of their poor mechanical properties. The
aim of this study was to determine the optimal condition for preparing a collagen
scaffold with biocompatibility and durability. An atelocollagen fiber suspension
was made and stored at -10 degrees C in a container that could be cooled from the
bottom to provide an orientation perpendicular to the collagen fiber and
facilitate cell infiltration into the scaffold. After freeze-drying the frozen
suspension, various collagen scaffolds were made by dehydrothermal (DHT)
treatment under different conditions (processing temperature: 120-160 degrees C
for 0-28 h). Sections of the obtained materials were embedded under the back skin
of rats, and the thickness and biocompatibility of the residual scaffold were
evaluated after 2 weeks. The number of foreign body giant cells was counted to
evaluate biocompatibility. Although the residual scaffold was thick, excessive
DHT treatment caused a strong foreign body reaction. Weak DHT treatment resulted
in a collagen scaffold with good biocompatibility but with reduced thickness.
Overall, these results showed the restricted optimal conditions to make a
collagen scaffold with good biocompatibility and ability to maintain sufficient
space for tissue regeneration. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater
Res Part B: Appl Biomater, 105B: 2301-2307, 2017.
PMID- 27486957
TI - The end of the hepatitis C burden: Really?
PMID- 27486958
TI - A procedure for sensory detection of androstenone in meat and meat products from
entire male pigs: Development of a panel training.
AB - This study represents a proposal for training sensory panels in androstenone
(AND) perception in meat and meat products. The procedure consists of four main
parts: (1) selection and training of a sensory panel (11 panelists) using
standards with Vaseline oil media as carriers of AND and skatole (SKA); (2)
developing a training method AND detection in meat; (3) dry cured meat product
and (4) cooked meat product. All candidates were able to distinguish between AND,
SKA and AND+SKA in Vaseline oil, order AND solutions with different
concentrations and classify them in the three categories: low, medium and high.
The panel was able to differentiate the meat in the three categories, but only
the high level in meat products. Due to the individual features in AND
perception, specific training for each type of product is required.
PMID- 27486959
TI - Effect of preservative addition on sensory and dynamic profile of Lucanian dry
sausages as assessed by quantitative descriptive analysis and temporal dominance
of sensations.
AB - The quantitative descriptive analysis (QDA) was combined with temporal dominance
of sensations (TDS) to assess the sensory properties of Lucanian dry-sausages
either added with nitrate, nitrite and l-ascorbic acid (NS), or not (NNS). Both
QDA and TDS differentiated the two groups of sausages. NNS products were
perceived with higher intensity of hardness (P<0.05) and tended to be perceived
with higher intensities of flavor (P<0.10), pepper (P<0.20), and oiliness
(P<0.20), while resulting lower in chewiness (P<0.20). TDS showed that in all the
sausages hardness was the first dominant attribute; then, in NNS products flavor
remained dominant until the end of tasting, whereas in NS products oiliness
prevailed. In conclusion, TDS showed that the perception of some textural
parameters, such as oiliness, during mastication was more dominant in NS
products, whereas using conventional QDA this attribute appeared higher in
sausages manufactured without preservatives. Therefore, TDS provided additional
information for the description and differentiation of Lucanian sausages.
PMID- 27486960
TI - Characterising variation in five genetic loci of cytomegalovirus during treatment
for congenital infection.
AB - Cytomegalovirus (CMV) is the most common congenital infection in humans and a
leading cause of sensorineural hearing loss. Ganciclovir (6 mg/kg twice daily for
42 days) has been shown to reduce hearing deterioration and is used in clinical
practice. Vaccines and passive administration of antibody are being evaluated in
randomized controlled trials in allograft candidates, women of childbearing age,
and pregnant women with primary CMV infection. To help define genetic variation
in each of the targets of these therapeutic interventions, we amplified and
sequenced genes UL97 (site utilised for ganciclovir phosphorylation), UL55
(glycoprotein B (gB) vaccine target) and UL128, UL130, and UL131a (specific
monoclonal antibody targets). Serial blood, saliva, and urine samples (total 120)
obtained from nine infants with symptomatic congenital CMV treated with 42 days'
ganciclovir were analyzed. All samples tested were UL97 wild type at baseline and
none developed mutations during treatment, showing no selection of resistance.
The prevalences of UL55 genotypes were 28% gB1, 22% gB2, 1% gB3, and mixed in 20%
samples. No mutations were noted in UL128-131a. Phylogenetic tree analysis showed
that sequences with variations were found in multiple body sites of individual
patients, so there was no evidence of body site compartmentalization of
particular strains of CMV. The significance of these results for changes in
diagnostic practices and therapeutic interventions against CMV are discussed. J.
Med. Virol. 89:502-507, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27486963
TI - Role of Operative Complexity Variables in Risk Adjustment for Patients With
Cancer.
PMID- 27486965
TI - The safety and efficacy of Diphoterine for ocular and cutaneous burns in humans.
AB - CONTEXT: Diphoterine, developed by the French company Prevor, is a polyvalent,
chelating, amphoteric and slightly hypertonic solution used in the management of
chemical cutaneous and ocular burns. While used extensively in Europe and Canada,
it is has not been approved by the United States Occupational Safety and Health
Administration (OSHA) as an alternative to the water-rinse method due to a lack
of evidence of its safety and efficacy on human subjects. An unbiased and
extensive systematic review was undertaken in order to better understand
Diphoterine's safety and efficaciousness on humans. OBJECTIVE: Review the safety
and efficacy of Diphoterine for treating chemical burns of the skin and eyes in
humans. METHODS: Data sources: Information sources included Pubmed, the National
Library of Medicine's Medline Database and the "Publications" sections of the
Prevor website. Search terms included Diphoterine, chemical burn, ocular burn and
cutaneous burn. STUDY SELECTION: Any study type published through a peer-reviewed
journal up to May 2016 was considered eligible. Published data must have included
Diphoterine in the treatment of chemical burns on the skin or eyes as well as
meet other specified criteria. Acceptable studies had to use either a
quantitative (e.g. number of work days lost) or qualitative (e.g. level of
erythema) approach when measuring cutaneous or ocular lesion outcomes. DATA
EXTRACTION: Independent assessment of article inclusion by two authors using
predefined criteria. RESULTS AND CONCLUSION: Diphoterine is safe and highly
effective in improving healing time, healing sequelae and pain management of
chemical burns on the skin and eyes of humans. Outcomes are significantly
improved when compared to water or a physiologic solution equivalent. We
recommend that this product be readily available to emergency responders and
companies that expose their employees to hazardous chemical substances in order
to improve healing sequelae, pain management and lost work days from these types
of burns.
PMID- 27486964
TI - Protein Kinase Czeta Inhibitor Promotes Resolution of Bleomycin-Induced Acute
Lung Injury.
AB - Protein kinase Czeta (PKCzeta) is highly expressed in the lung, where it plays
several regulating roles in the pathogenesis of acute lung injury (ALI).
Proliferation and differentiation of integrin beta4+ distal lung epithelial
progenitor cells seem to play a key role in proper lung regeneration. We
investigated the effects of a myristoylated PKCzeta inhibitor (PKCzetai) in a
murine model of bleomycin-induced ALI. After intratracheal injury, we treated
mice three times a week with PKCzetai or its vehicle, DMSO. We found that mice
injured with bleomycin and then treated with PKCzetai for one week showed
decreased activation of PKCzeta, improved lung compliance, and decreased lung
protein permeability compared to injured mice treated with DMSO. Mice treated
continuously with PKCzetai for 6 weeks showed reduced evidence of lung fibrosis
by computed tomographic images, decreased lung collagen deposition, and decreased
active transforming growth factor-beta in the bronchoalveolar lavage fluid. In
addition, we found an increased number of lung beta4+ cells compared to DMSO at
Week 6. Therefore, we grew isolated integrin beta4+ lung progenitor cells in the
presence of PKCzetai or DMSO and found that beta4+ cells treated with PKCzetai
proliferated more in vitro compared to DMSO. We conclude that the use of a
PKCzetai promotes resolution of lung fibrosis in a bleomycin ALI model and
increases the number of beta4+ progenitor cells with regenerative potential in
the lung.
PMID- 27486966
TI - Imagery Rescripting: The Impact of Conceptual and Perceptual Changes on Aversive
Autobiographical Memories.
AB - BACKGROUND: Imagery rescripting (ImRs) is a process by which aversive
autobiographical memories are rendered less unpleasant or emotional. ImRs is
thought only to be effective if a change in the meaning-relevant (semantic)
content of the mental image is produced, according to a cognitive hypothesis of
ImRs. We propose an additional hypothesis: that ImRs can also be effective by the
manipulation of perceptual features of the memory, without explicitly targeting
meaning-relevant content. METHODS: In two experiments using a within-subjects
design (both N = 48, community samples), both Conceptual-ImRs-focusing on
changing meaning-relevant content-and Perceptual-ImRs-focusing on changing
perceptual features-were compared to Recall-only of aversive autobiographical
image-based memories. An active control condition, Recall + Attentional Breathing
(Recall+AB) was added in the first experiment. In the second experiment, a
Positive-ImRs condition was added-changing the aversive image into a positive
image that was unrelated to the aversive autobiographical memory. Effects on the
aversive memory's unpleasantness, vividness and emotionality were investigated.
RESULTS: In Experiment 1, compared to Recall-only, both Conceptual-ImRs and
Perceptual-ImRs led to greater decreases in unpleasantness, and Perceptual-ImRs
led to greater decreases in emotionality of memories. In Experiment 2, the
effects on unpleasantness were not replicated, and both Conceptual-ImRs and
Perceptual-ImRs led to greater decreases in emotionality, compared to Recall
only, as did Positive-ImRs. There were no effects on vividness, and the ImRs
conditions did not differ significantly from Recall+AB. CONCLUSIONS: Results
suggest that, in addition to traditional forms of ImRs, targeting the meaning
relevant content of an image during ImRs, relatively simple techniques focusing
on perceptual aspects or positive imagery might also yield benefits. Findings
require replication and extension to clinical samples.
PMID- 27486967
TI - Two-dimensional versus three-dimensional laparoscopy in surgical efficacy: a
systematic review and meta-analysis.
AB - BACKGROUND: Laparoscopy is a revolutionary technique in modern surgery. However,
the comparative efficacy between two-dimensional laparoscopy and three
dimensional laparoscopy remains in uncertainty. Therefore we performed this
systematic review and meta-analysis in order to seek for answers. METHODS:
Databases of PubMed, Web of Science, EMBASE and Cochrane Library were carefully
screened. Clinical trials comparing two-dimensional versus three-dimensional
laparoscopy were included for pooled analysis. Observational and randomized
trials were methodologically appraised by Newcastle-Ottawa Scale and Revised
Jadad's Scale respectively. Subgroup analyses were additionally conducted to
clarify the potential confounding elements. Outcome stability was examined by
sensitivity analysis, and publication bias was analyzed by Begg's test and
Egger's test. RESULTS: 21 trials were screened out from the preliminary 3126
records. All included studies were high-quality in methodology, except for Bilgen
2013 and Ruan 2015. Three-dimensional laparoscopy was superior to two-dimensional
laparoscopy in terms of surgical time (P < 0.00001), blood loss (P = 0.01),
perioperative complications (P = 0.04) and hospital stay (P = 0.03).
Additionally, both techniques demonstrated comparable results of secondary
endpoints, including drainage volume (P = 0.74), drainage time (P = 0.26),
numbers of retrieved lymphnodes (P = 0.85), hospital expenses (P = 0.49),
anastomosis time in prostatectomy (P=0.15) and 6-month continence rate (P =
0.61). The pooled outcomes of primary endopoints were verified to be stable by
sensitivity analysis. Although Begg's test (P = 0.215) and Egger's test (P =
0.003) revealed that there was publication bias across included studies, Trim-and
Fill method confirmed that the results remained stable. CONCLUSION: Three
dimensional laparoscopy is a preferably surgical option against two-dimensional
laparoscopy due to its better surgical efficacy.
PMID- 27486968
TI - Association between dietary nitrate and nitrite intake and sitespecific cancer
risk: evidence from observational studies.
AB - Epidemiological studies have reported inconsistent findings on the association
between dietary nitrate and nitrite intake and cancer risk. We performed a meta
analysis of epidemiological studies to summarize available evidence on the
association between dietary nitrate and nitrite intake and cancer risk from
published prospective and case-control studies. PubMed database was searched to
identify eligible publications through April 30th, 2016. Study-specific relative
risks (RRs) with corresponding 95% confidence interval (CI) from individual
studies were pooled by using random- or fixed- model, and heterogeneity and
publication bias analyses were conducted. Data from 62 observational studies, 49
studies for nitrates and 51 studies for nitrites, including a total of 60,627
cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary
nitrate intake was inversely associated with gastric cancer risk (RR = 0.78;
95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary
nitrite intake was positively associated with adult glioma and thyroid cancer
risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05),
respectively. No significant associations were found between dietary
nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal
cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis
provided modest evidence that positive associations of dietary nitrate and
negative associations of dietary nitrite with certain cancers.
PMID- 27486969
TI - CRISPR Cas9-guided chromatin immunoprecipitation identifies miR483 as an
epigenetic modulator of IGF2 imprinting in tumors.
AB - The normally imprinted insulin-like growth factor II (IGF2) gene is aberrantly
upregulated in a variety of human malignancies, yet the mechanisms underlying
this dysregulation are still poorly defined. In this report, we used a CRISPR
Cas9-guided chromatin immunoprecipitation assay to characterize the molecular
components that participate in the control of IGF2 gene expression in human tumor
cells. We found that miR483, an oncogenic intronic miRNA, binds to the most
upstream imprinted IGF2 promoter, P2. Ectopic expression of miR483 induced
upregulation of IGF2 expression, in parallel with an increase in tumor cell
proliferation, migration, invasion, and tumor colony formation. miR483 induced
loss of IGF2 imprinting by altering the epigenotype at P2, with reduction in
histone H3K27 methylation and a decrease in chromatin binding of two imprinting
regulatory factors, CTCF and SUZ12. This study identifies a new role for miR483
in the regulation of IGF2 gene expression through the alteration of the promoter
epigenotype.
PMID- 27486970
TI - IGF-II induced by hepatitis B virus X protein regulates EMT via SUMO mediated
loss of E-cadherin in mice.
AB - Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading
cause of cancer mortality. Prognosis of this disease largely depends on its
stage. An Enlarged liver, due to dysplasia, may be a critical point in the multi
step progression to HCC. The mechanism underlying hepatomegaly in human and mouse
models are poorly understood. We previously reported we observed enlarged liver
in hepatitis B virus X protein (HBx) expressing mice (HBx mice). Here we identify
the critical role of HBx induced IGF-II in hepatomegaly in mice and abnormal cell
growth in human hepatoma cells. We found that HBx induced IGF-II is essential to
induce epithelial-mesenchymal transition (EMT) through loss of E-cadherin. In
mouse liver, loss of E-cadherin was mediated by post-translational regulation, at
least in part, by protease and SUMOylation not by transcriptional regulation. In
contrast, in hepatoma cell line (HepG2 cells) Akt signal pathway controls the
mRNA expression level of EMT-related transcription factors, especially Twist, in
addition to post- translational modification through SUMOylation. Thus, IGF-II
mediated loss of E-cadherin is central in developing hepatomegaly in mice and
abnormal cell growth in the hepatoma cell line. HBx induced IGF-II represents a
potential biomarker, which is also a therapeutic target in HCC.
PMID- 27486971
TI - IRES-dependent translation of the long non coding RNA meloe in melanoma cells
produces the most immunogenic MELOE antigens.
AB - MELOE-1 and MELOE-2, two highly specific melanoma antigens involved in T cell
immunosurveillance are produced by IRES-dependent translation of the long " non
coding " and polycistronic RNA, meloe. In the present study, we document the
expression of an additional ORF, MELOE-3, located in the 5' region of meloe. Data
from in vitro translation experiments and transfection of melanoma cells with
bicistronic vectors documented that MELOE-3 is exclusively translated by the
classical cap-dependent pathway. Using a sensitive tandem mass spectrometry
technique, we detected the presence of MELOE-3 in total lysates of both melanoma
cells and normal melanocytes. This contrasts with our previous observation of the
melanoma-restricted expression of MELOE-1 and MELOE-2. Furthermore, in vitro
stimulation of PBMC from 6 healthy donors with overlapping peptides from MELOE-1
or MELOE-3 revealed a very scarce MELOE-3 specific T cell repertoire as compared
to the abundant repertoire observed against MELOE-1. The poor immunogenicity of
MELOE-3 and its expression in melanocytes is consistent with an immune tolerance
towards a physiologically expressed protein. In contrast, melanoma-restricted
expression of IRES-dependent MELOE-1 may explain its high immunogenicity. In
conclusion, within the MELOE family, IRES-dependent antigens represent the best T
cell targets for immunotherapy of melanoma.
PMID- 27486972
TI - A role for activated Cdc42 in glioblastoma multiforme invasion.
AB - Cdc42 is a Rho-GTPase which plays a major role in regulating cell polarity and
migration by specifying the localization of filopodia. However, the role of Cdc42
in GBM invasion has not been thoroughly investigated. We generated stable
doxycycline-inducible clones expressing wild type (WT)-, constitutively active
(CA)-, and dominant negative (DN)-Cdc42 in three different human glioma cell
lines. Expression of CA-Cdc42 significantly increased the migration and invasive
properties of malignant glioma cells compared to WT and DN-Cdc42 cell clones, and
this was accompanied by a greater number of filopodia and focal adhesion
structures which co-localize with phosphorylated focal adhesion kinase (FAK). By
mass spectrometry and immunoprecipitation studies, we demonstrated that activated
Cdc42 binds to IQGAP1. When implanted orthotopically in mice, the CA-Cdc42
expressing glioma cells exhibited enhanced local migration and invasion, and led
to larger tumors, which significantly reduced survival. Using the Cancer Genome
Atlas dataset, we determined that high Cdc42 expression is associated with poorer
progression free survival, and that Cdc42 expression is highest in the proneural
and neural subgroups of GBM. In summary, our studies demonstrate that activated
Cdc42 is a critical determinant of the migratory and invasive phenotype of
malignant gliomas, and that its effect may be mediated, at least in part, through
its interaction with IQGAP1 and phosphorylated FAK.
PMID- 27486973
TI - Critical role of androgen receptor level in prostate cancer cell resistance to
new generation antiandrogen enzalutamide.
AB - Enzalutamide is an androgen receptor (AR) inhibitor approved for therapy of
metastatic castration resistant prostate cancer. However, clinical application
revealed that 30 to 40% of patients acquire resistance after a short period of
treatment. Currently, the molecular mechanisms underlying such resistances are
not completely understood, partly due to a lack of model systems. In the present
study we established three different cellular models of enzalutamide resistance
including a cell line with wild type AR (LAPC4), DuCaP cells which overexpress
wild-type AR, as well as a cell which has been adapted to long term androgen
ablation (LNCaP Abl) and harbors the AR T878A mutation. After 10 months of
cultivation, sustained growth in the presence of enzalutamide was achieved. When
compared to controls, resistant cells exhibit significantly decreased sensitivity
to enzalutamide as measured with 3[H]thymidine incorporation and WST assay.
Moreover, these cell models exhibit partly re-activated AR signaling despite
presence of enzalutamide. In addition, we show that enzalutamide resistant cells
are insensitive to bicalutamide but retain considerable sensitivity to
abiraterone. Mechanistically, enzalutamide resistance was accompanied by
increased AR and AR-V7 mRNA and protein expression as well as AR gene
amplification, while no additional AR mutations have been identified.
PMID- 27486974
TI - Telomere status in chronic lymphocytic leukemia with TP53 disruption.
AB - In chronic lymphocytic leukemia (CLL), telomere dysfunction is associated with
poor outcomes. TP53 is involved in cellular responses to dysfunctional telomeres,
and its inactivation is the strongest adverse prognostic factor for CLL. Given
the biological relationship between TP53 and telomeres, and their prognostic
value, it is important to improve our understanding of the impact of TP53
alterations on telomeres. We performed a comprehensive study of the deletions and
mutations of the TP53 gene and telomere parameters, including hTERT and the
shelterin complex, in 115 CLL patients. We found that any type of TP53 alteration
was associated with very short telomeres and high hTERT expression, independently
of other biological CLL features. Patients with disrupted TP53 showed telomere
deletions and chromosomal end-to-end fusions in cells with complex karyotypes.
TP53 disruption was characterized by downregulation of shelterin genes.
Interestingly, low expression of POT1, TPP1 and TIN2 was also found in some
patients with wild-type TP53 and had an adverse impact on progression-free
survival after standard genotoxic therapy. In conclusion, we have demonstrated
that patients with disrupted TP53 have severe telomere dysfunction and high
genomic instability. Thus, the telomeric profile could be tested as a biomarker
in CLL patients treated with new therapeutic agents.
PMID- 27486975
TI - Poor recognition of O6-isopropyl dG by MGMT triggers double strand break-mediated
cell death and micronucleus induction in FANC-deficient cells.
AB - Isopropyl methanesulfonate (IPMS) is the most potent genotoxic compound among
methanesulfonic acid esters. The genotoxic potential of alkyl sulfonate esters is
believed to be due to their alkylating ability of the O6 position of guanine.
Understanding the primary repair pathway activated in response to IPMS-induced
DNA damage is important to profile the genotoxic potential of IPMS. In the
present study, both chicken DT40 and human TK6 cell-based DNA damage response
(DDR) assays revealed that dysfunction of the FANC pathway resulted in higher
sensitivity to IPMS compared to EMS or MMS. O6-alkyl dG is primarily repaired by
methyl guanine methyltransferase (MGMT), while isopropyl dG is less likely to be
a substrate for MGMT. Comparison of the cytotoxic potential of IPMS and its
isomer n-propyl methanesulfonate (nPMS) revealed that the isopropyl moiety avoids
recognition by MGMT and leads to higher cytotoxicity. Next, the micronucleus (MN)
assay showed that FANC deficiency increases the sensitivity of DT40 cells to MN
induction by IPMS. Pretreatment with O6-benzyl guanine (OBG), an inhibitor of
MGMT, increased the MN frequency in DT40 cells treated with nPMS, but not IPMS.
Lastly, IPMS induced more double strand breaks in FANC-deficient cells compared
to wild-type cells in a time-dependent manner. All together, these results
suggest that IPMS-derived O6-isopropyl dG escapes recognition by MGMT, and the
unrepaired DNA damage leads to double strand breaks, resulting in MN induction.
FANC, therefore, plays a pivotal role in preventing MN induction and cell death
caused by IPMS.
PMID- 27486976
TI - Neuropilin-1 is a receptor for extracellular miRNA and AGO2/miRNA complexes and
mediates the internalization of miRNAs that modulate cell function.
AB - Extracellular miRNAs are increasingly studied as markers for specific diseases.
They are released in biological fluids in a remarkably stable form, and may play
a role in intercellular communication. They are thought to be protected against
degradation by either encapsulation within microparticles, or by binding to
proteins (mostly AGO2). The particulate forms may be internalized by endocytosis
or membrane fusion, but the protein-bound forms require a receptor mechanism for
their uptake. A major question is whether there are natural cell-membrane
receptors that capture and internalize protein-bound functional miRNAs. We
examined neuropilin-1 (NRP1), in view of its properties as a receptor for many
ligands, including growth factors such as vascular endothelial growth factor
(VEGF), and efficiency at mediating ligand internalization. It is expressed by
endothelial cells, many other normal cell types, and cancer cells. Here, we
report that NRP1 binds miRNAs with high affinity, and promotes their entry into
the cell. Furthermore, the internalized miRNAs remain functional, as they
specifically regulate proliferation and migration of cancer cells, as well as
tube formation by human endothelial cells. Anti-NRP1 antibodies or NRP1 siRNA
knockdown block miRNA effects, further confirming NRP1-mediated uptake. VEGF does
not compete with miRNAs for binding to NRP1. In addition, NRP1 binds
extracellular AGO2 (carrying miRNA or not), and internalizes AGO2/miRNA
complexes. Because miRNA bound to AGO2 appears to the most abundant form in body
fluids, this may have important physiological and pathological effects.
PMID- 27486977
TI - Improved survival of patients with hepatocellular carcinoma and disparities by
age, race, and socioeconomic status by decade, 1983-2012.
AB - Hepatocellular carcinoma (HCC), accounting for the majority of liver cancer, is a
highly aggressive malignancy with poor prognosis and therefore adds up the
financial burden. Incidence data of HCC in three decades during 1983-2012 were
extracted from the Surveillance, Epidemiology, and End Results (SEER) database
with incidence rates of 1.9, 3.1 and 4.9 per 100,000 respectively. In addition,
to evaluate the survival changes in the same period, a total of 63,640 HCC cancer
cases were accessed from SEER database. The six-month relative survival rates
improved each decade from 31.0% to 42.9% to 57.2% and the higher increase can be
seen in the last two decades. More importantly, the disparities of survival among
different racial groups and socioeconomic status (SES) were confirmed by the
inferiority of survival in Black race and high-poverty group respectively. This
research analyzed the incidence and survival data of HCC in the past three
decades and may help predict the future trends of incidence and survival.
Furthermore, this study may help better design healthcare policies and clinical
management programs to balance the disparities of survival between SES groups,
races, ages and sexes confirmed in this study and thereby improve the clinical
management of HCC.
PMID- 27486978
TI - Metformin use and cervical cancer risk in female patients with type 2 diabetes.
AB - This study evaluated whether metformin may affect the risk of cervical cancer.
The reimbursement databases of the Taiwan's National Health Insurance were used.
Female patients with type 2 diabetes at an onset age of 25-74 years during 1999
2005 and newly treated with metformin (n=132971, "ever users of metformin") or
other antidiabetic drugs (n=6940, "never users of metformin") were followed for
at least 6 months until December 31, 2011. The treatment effect of metformin (for
ever versus never users, and for tertiles of cumulative duration of therapy) was
estimated by Cox regression incorporated with the inverse probability of
treatment weighting using propensity score. Analyses were also conducted in a 1:1
matched pair cohort based on 8 digits of propensity score. Results showed that
the respective numbers of incident cervical cancer in ever users and never users
were 438 (0.33%) and 38 (0.55%), with respective incidences of 68.29 and 121.38
per 100,000 person-years. The overall hazard ratio suggested a significantly
lower risk in metformin users (0.558, 95% confidence intervals: 0.401-0.778). In
tertile analyses, the hazard ratios (95% confidence intervals) for the first
(<23.0 months), second (23.0-47.9 months) and third (>47.9 months) tertile of
cumulative duration were 1.272 (0.904-1.790), 0.523 (0.366-0.747) and 0.109
(0.070-0.172), respectively. Findings were supported by the analyses in the
matched cohort. In conclusion, metformin may significantly reduce the risk of
cervical cancer, especially when the cumulative duration is more than 2 years.
PMID- 27486980
TI - Association of lncRNA H19 rs217727 polymorphism and cancer risk in the Chinese
population: a meta-analysis.
AB - Reports on the relationship between the lncRNA H19 rs217727 polymorphism and the
risk of cancer in the Chinese population have been inconsistent. Therefore, we
performed a meta-analysis to evaluate this association, by searching the Embase,
PubMed, Web of Science, Wanfang, and CNKI databases. Four case-control studies
with 3,157 cases and 3,564 controls were selected for this meta-analysis. The
odds ratios with 95% confidence intervals were examined using the random effect
model. Allelic (A vs. G), dominant (AA + GA vs. GG), recessive (AA vs. GA + GG),
and additive (AA vs. GG) genetic models were used to determine the association.
Overall, no significant association was observed between the rs217727
polymorphism and cancer susceptibility in any of the four genetic models.
Sensitivity analysis revealed that the results were stable in the allelic and
dominant genetic models, but those from the recessive and additive models were
unstable, which should be treated with caution. Our meta-analysis suggests that
the lncRNA H19 rs217727 polymorphism might not be associated with overall cancer
risk. However, well-designed, large-scale studies with different ethnic
populations need to be conducted in the future to elucidate the potential
association.
PMID- 27486981
TI - Targeted deep sequencing improves outcome stratification in chronic
myelomonocytic leukemia with low risk cytogenetic features.
AB - Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic
myelomonocytic leukemia (CMML), while gene mutations are present in >90% of
cases. Patients with low risk cytogenetic features account for 80% of CMML cases
and often fall into the low risk categories of CMML prognostic scoring systems,
but the outcome differs considerably among them. We performed targeted deep
sequencing of 83 myeloid-related genes in 56 CMML patients with low risk
cytogenetic features or uninformative conventional cytogenetics (CC) at
diagnosis, with the aim to identify the genetic characteristics of patients with
a more aggressive disease. Targeted sequencing was also performed in a subset of
these patients at time of acute myeloid leukemia (AML) transformation. Overall,
98% of patients harbored at least one mutation. Mutations in cell signaling genes
were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS
correlated with higher risk features and shorter overall survival (OS) and
progression free survival (PFS). Patients with SRSF2 mutations associated with
poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter
PFS. A decrease in OS and PFS was observed as the number of adverse risk gene
mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML
specific scoring system (CPSS) and presence of adverse risk gene mutations
remained significant for OS, while CPSS and TET2wt were predictive of PFS. These
results confirm that mutation analysis can add prognostic value to patients with
CMML and low risk cytogenetic features or uninformative CC.
PMID- 27486979
TI - Functional single nucleotide polymorphisms within the cyclin-dependent kinase
inhibitor 2A/2B region affect pancreatic cancer risk.
AB - The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one
of the most commonly somatically mutated genes in pancreatic cancer, rare
germline mutations have been found to be associated with increased risk of
developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has
been suggested to play a critical role both in pancreatic cancer onset and
prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes
the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development
of cancer in various organs. However, association between the common genetic
variability in this region and pancreatic cancer risk is not clearly understood.
We sought to fill this gap in a case-control study genotyping 13 single
nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC)
patients and 6,111 controls in the context of the Pancreatic Disease Research
(PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was
associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01
1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant
is reported to be a mir-SNP that, by changing the binding site of one or more
miRNAs, could influence the normal cell cycle progression and in turn increase
PDAC risk. In conclusion, we observed a novel association in a pleiotropic region
that has been found to be of key relevance in the susceptibility to various types
of cancer and diabetes suggesting that the CDKN2A/B locus could represent a
genetic link between diabetes and pancreatic cancer risk.
PMID- 27486982
TI - Oncostatin M suppresses metastasis of lung adenocarcinoma by inhibiting SLUG
expression through coordination of STATs and PIASs signalings.
AB - Oncostatin M (OSM) is linked with multiple biological responses including growth
and differentiation. Previous reports showed inhibitory effects of OSM in tumor
progression while others showed promoting effects. The dual role of OSM in the
development of various cancers is still unclear. We previously described OSM
mediated SLUG suppression, leading to repressed metastasis of lung adenocarcinoma
(LAC) cells. However, the underlying mechanism remains elusive. Here, we showed
that OSM suppresses SLUG express in LAC cells through a STAT1-dependent
transcriptional inhibition. Knockdown of STAT1 reversed the OSM-suppressed SLUG
expression and rescued the OSM-mediated inhibition of cell proliferation,
migration, and invasion in vitro, as well as pulmonary metastasis in vivo. STAT1
suppressed SLUG transcription through binding to its promoter region in response
to OSM. Furthermore, PIAS4, a co-repressor of STAT, and HDAC1 were able to bind
to STAT1 on SLUG promoter region, resulting in reduced H3K9 acetylation and
suppressed SLUG expression upon OSM treatment. In contrast, PIAS3 bound to
activated STAT3, another effector of OSM, in response to OSM and blocked the
binding of STAT3 to SLUG promoter region, preventing STAT3-dependent activation
of SLUG transcription. Our findings suggested that OSM suppresses SLUG expression
and tumor metastasis of LAC through inducing the inhibitory effect of the STAT1
dependent pathway and suppressing the activating effect of STAT3-dependent
signaling. These results can serve as a scientific basis for the potential
therapeutic intervention of OSM in cancer cells.
PMID- 27486984
TI - Age is associated with time in therapeutic range for warfarin therapy in patients
with atrial fibrillation.
AB - BACKGROUND: Warfarin is the most prescribed oral anticoagulant used for
preventing stroke in patients with atrial fibrillation. Time in the therapeutic
range (TTR) has been accepted as the best method to evaluate the quality of
warfarin therapy. The main aim of the present study was to evaluate the impact of
variables on the time in the therapeutic range for warfarin therapy in patients
with atrial fibrillation from a referral cardiovascular hospital. METHODS: This
retrospective study included 443 patients were included (190 patients with age <
65 years and 253 patients with age >=65 years) from 2011 to 2014 and TTR was
computed according to Rosendaal's method. RESULTS: Patients with age >=65 years
had higher TTR value (67+/-22%) compared with patients with < 65 years (60+/-24%)
(p = 0.004). In a linear regression model, only age >=65 years emerged as a
significant predictor of greater TTR values. In multivariate logistic regression
model, the variable age >=65 years was associated with higher OR for having a TTR
higher than the median value (OR = 2.17, p < 0.001). CONCLUSION: We suggest that
the age influenced TTR through greater drug adherence. Strategies for increasing
drug adherence might improve quality of warfarin anticoagulation.
PMID- 27486983
TI - Targeting signal transduction pathways of cancer stem cells for therapeutic
opportunities of metastasis.
AB - Tumor comprises of heterogeneous population of cells where not all the
disseminated cancer cells have the prerogative and "in-build genetic cues" to
form secondary tumors. Cells with stem like properties complemented by key
signaling molecules clearly have shown to exhibit selective growth advantage to
form tumors at distant metastatic sites. Thus, defining the role of cancer stem
cells (CSC) in tumorigenesis and metastasis is emerging as a major thrust area
for therapeutic intervention. Precise relationship and regulatory mechanisms
operating in various signal transduction pathways during cancer dissemination,
extravasation and angiogenesis still remain largely enigmatic. How the crosstalk
amongst circulating tumor cells (CTC), epithelial mesenchymal transition (EMT)
process and CSC is coordinated for initiating the metastasis at secondary
tissues, and during cancer relapse could be of great therapeutic interest. The
signal transduction mechanisms facilitating the dissemination, infiltration of
CSC into blood stream, extravasations, progression of metastasis phenotype and
angiogenesis, at distant organs, are the key pathologically important
vulnerabilities being elucidated. Therefore, current new drug discovery focus has
shifted towards finding "key driver genes" operating in parallel signaling
pathways, during quiescence, survival and maintenance of stemness in CSC.
Understanding these mechanisms could open new horizons for tackling the issue of
cancer recurrence and metastasis-the cause of ~90% cancer associated mortality.
To design futuristic & targeted therapies, we propose a multi-pronged strategy
involving small molecules, RNA interference, vaccines, antibodies and other
biotechnological modalities against CSC and the metastatic signal transduction
cascade.
PMID- 27486985
TI - Combination of specific allergen and probiotics induces specific regulatory B
cells and enhances specific immunotherapy effect on allergic rhinitis.
AB - The therapeutic efficacy of allergen specific immunotherapy (SIT) on allergic
diseases is to be improved. Probiotics can regulate immune response. This study
aims to promote the effect of SIT on allergic rhinitis (AR) by co-administration
with Clostridium butyricum (Cb). In this study, patients with AR sensitized to
mite allergens were enrolled to this study, and treated with SIT or/and Cb. The
therapeutic efficacy was evaluated by the total nasal symptom scores (NSS),
medication scores, serum specific IgE levels and T helper (Th)2 cytokine levels.
The improvement of immune regulation in the AR patients was assessed by
immunologic approaches. The results showed that treating AR patients with SIT
alone markedly reduced NSS and medication scores; but did not alter the serum
specific IgE, Th2 cytokines and skin prick test (SPT) index. The clinical
symptoms on AR in SIT group relapsed one month after stopping SIT. Co
administration of Cb significantly enhanced the efficacy of SIT on AR as shown by
suppression of NSS, medication scores, serum specific IgE, Th2 cytokines and SPT
index; the regulatory B cell frequency was also markedly increased. Such an
effect on AR was maintained throughout the observation period even after stopping
the treatment. Butyrate blocked the activation of histone deacetylase-1, the
downstream activities of epsilon chain promoter activation, and the IgE
production in the antigen specific B cells. On the other hand, butyrate induced
the IL-10 expression in B cells with a premise of the B cell receptor activation
by specific antigens. In conclusion, administration with Cb can markedly enhance
the efficacy of SIT on AR.
PMID- 27486986
TI - miRNA-193a-5p repression of p73 controls Cisplatin chemoresistance in primary
bone tumors.
AB - Osteosarcoma and Ewing Sarcoma are the two most common types of Bone Sarcomas,
principally localized at the long bones of the extremities and mainly affecting
adolescents and young adults. Cisplatin is one of the current options in the
therapeutic arsenal of drugs available to cure these aggressive cancers.
Unfortunately, chemoresistance against this agent is still a major cause of
patient relapse. Thus, a better understanding of the molecular pathways by which
these drugs induce cancer cell death, together with a better delineation of the
origins of chemoresistance are required to improve the success rate of current
treatments. Furthermore, as p53 is frequently mutated in Bone Sarcomas, other
pathways in these cancers must mediate drug-induced cell death. Here, we
demonstrate for the first time that TAp73beta, a p53-family protein, is
implicated in Cisplatin-induced apoptosis of Bone Sarcomas'. Furthermore, while
acquired resistance developed by cancer cells against such drugs can have
multiple origins, it is now well accepted that epigenetic mechanisms involving
microRNAs (miRNAs) are one of them. We show that miRNA-193a-5p modulates the
viability, the clonogenic capacity and the Cisplatin-induced apoptosis of the
Bone Sarcoma cells through inhibition of TAp73beta. Collectively, these results
shed light on the involvement of miR-193a-5p in Cisplatin chemoresistance of Bone
Sarcomas', and they open the road to new therapeutic opportunities provided by
targeting the miR-193a-5p/TAp73beta axis in the context of these malignancies.
PMID- 27486989
TI - The Associations of IL-6, IFN-gamma, TNF-alpha, IL-10, and TGF-beta1 Functional
Variants with Acute Myeloid Leukemia in Turkish Patients.
AB - AIM: It has been suggested that cytokine dysregulation could be associated with
pathogenesis, progression, and survival in acute myeloid leukemia (AML). The
purpose of this study was to evaluate the relationship of functional single
nucleotide polymorphisms (SNPs) in cytokine gene and cytokine expression levels
with AML. MATERIALS AND METHODS: Peripheral blood samples were collected from 42
patients with AML and 85 healthy individuals. Eight SNPs in five cytokine genes,
including interleukin 6 (IL-6), interferon-gamma (IFN-gamma), tumor necrosis
factor-alpha (TNF-alpha), interleukin-10 (IL-10), and transforming growth factor
beta 1 (TGF-beta1), were analyzed using the polymerase chain reaction sequence
specific primer method. RESULTS: We found that the frequencies of the TNF-alpha (
308) GG genotype and G allele were significantly higher in the patients with AML
compared to the healthy control group (p = 0.020 and 0.014). The AML patients had
significantly lower frequencies of the CC genotype and C allele of the IL-10 (
819 SNP), the G allele of the IL-10 (-1082 SNP), the CC genotype and C allele of
the IL-10 (-592 SNP), and the codon 25 GC genotype of TGF-beta1, (p = 0.024, p =
0.012, p = 0.038, p = 0.024, p = 0.012, p = 0.028, respectively). However, no
significant differences were found between AML and healthy control groups with
respect to the distributions of genotypes in IL-6, IFN-gamma, IL-10 (-1082), TGF
beta1 (codon 10), and haplotypes of IL-10, TGF-beta1 gene. CONCLUSION: Our
results suggest that functional variants of the TNF-alpha, IL-10, and TGF-beta1
genes may have a significant association with the etiopathogenesis of AML.
Further studies with larger groups and different ethnicities are needed to
determine the impact of cytokine variants on the risk of developing AML.
PMID- 27486987
TI - Coexistence of JAK2 and CALR mutations and their clinical implications in
patients with essential thrombocythemia.
AB - Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent
mutations in essential thrombocythemia (ET), and both are reported to be mutually
exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN)
patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for
coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3%
in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and
2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%)
of 167 ET patients. Clinical characteristics, progression-free survival (PFS),
and elapsed time to achieve partial remission across 4 groups (JAK2+/CALR+,
JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR-) were reviewed. The JAK2+/CALR- group had
higher leukocyte counts and hemoglobin levels and more frequent thrombotic events
than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease
phenotype and the clinical features of MPN patients rather than do CALR mutation.
JAK2+ groups showed a tendency of poor PFS than JAK2- groups regardless of CALR
mutation. CALR+ was a predictor of late response to the treatment. Our study also
showed that thrombosis was more frequent in ET patients with type 2 CALR
mutations than in those with type 1 CALR mutations.
PMID- 27486988
TI - Epigenetic reprogramming and aberrant expression of PRAME are associated with
increased metastatic risk in Class 1 and Class 2 uveal melanomas.
AB - BACKGROUND: We previously identified PRAME as a biomarker for metastatic risk in
Class 1 uveal melanomas. In this study, we sought to define a threshold value for
positive PRAME expression (PRAME+) in a large dataset, identify factors
associated with PRAME expression, evaluate the prognostic value of PRAME in Class
2 uveal melanomas, and determine whether PRAME expression is associated with
aberrant hypomethylation of the PRAME promoter. RESULTS: Among 678 samples
analyzed by qPCR, 498 (73.5%) were PRAME- and 180 (26.5%) were PRAME+. Class 1
tumors were more likely to be PRAME-, whereas Class 2 tumors were more likely to
be PRAME+ (P < 0.0001). PRAME expression was associated with shorter time to
metastasis and melanoma specific mortality in Class 2 tumors (P = 0.01 and P =
0.02, respectively). In Class 1 tumors, PRAME expression was directly associated
with SF3B1 mutations (P < 0.0001) and inversely associated with EIF1AX mutations
(P = 0.004). PRAME expression was strongly associated with hypomethylation at 12
CpG sites near the PRAME promoter. MATERIALS AND METHODS: Analyses included PRAME
mRNA expression, Class 1 versus Class 2 status, chromosomal copy number, mutation
status of BAP1, EIF1AX, GNA11, GNAQ and SF3B1, and genomic DNA methylation
status. Analyses were performed on 555 de-identified samples from Castle
Biosciences, 123 samples from our center, and 80 samples from the TCGA.
CONCLUSIONS: PRAME is aberrantly hypomethylated and activated in Class 1 and
Class 2 uveal melanomas and is associated with increased metastatic risk in both
classes. Since PRAME has been successfully targeted for immunotherapy, it may
prove to be a companion prognostic biomarker.
PMID- 27486990
TI - Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract,
but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.
AB - Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen,
but more than 70% of patients fail to seek treatment due to the asymptomatic
nature of these infections. Women suffer from numerous complications from chronic
chlamydial infections, which include pelvic inflammatory disease and infertility.
We previously demonstrated in culture that host cell nectin-1 knockdown
significantly reduced chlamydial titers and inclusion size. Here, we sought to
determine whether nectin-1 was required for chlamydial development in vivo by
intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring
chlamydial shedding by chlamydial titer assay. We observed a significant
reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin
1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical
staining in mouse cervical tissue confirmed that there are fewer chlamydial
inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial
infections are becoming a substantial health burden, though little is known
regarding the pathogenesis of these infections. We therefore established a novel
male murine model of rectal chlamydial infection, which we used to determine
whether nectin-1 is required for anorectal chlamydial infection in male mice. In
contrast to the data from vaginal infection, no difference in rectal chlamydial
shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared.
Through the use of these two models, we have demonstrated that nectin-1 promotes
chlamydial infection in the female genital tract but does not appear to
contribute to rectal infection in male mice. These models could be used to
further characterize tissue and sex related differences in chlamydial infection.
PMID- 27486991
TI - Correlates of Concurrent Khat and Tobacco Use in Yemen.
AB - BACKGROUND: Habitual substance use poses public health threat. This is a growing
concern in countries where one or more substances are commonly used. Many
individuals in Middle Eastern and East African countries use khat (Catha edulis),
a stimulant often accompanied by smoking. However, few systematic attempts have
been made to characterize patterns of concurrent khat and tobacco use.
OBJECTIVES: To examine correlates such as gender and patterns of khat and tobacco
use in concurrent users and khat-only users. METHODS: This study used a cross
sectional design with a face-to-face interview method including 151 (74 women)
concurrent users of khat and tobacco and 141 (76 women) khat-only users in Yemen.
Data collection was completed in 2012. Analysis of variance (ANOVA) and logistic
regressions were conducted to examine gender and khat use group differences in
use patterns. RESULTS: Reported frequency and intensity of khat use were greater
in men than in women. Men and women khat users used different tobacco products
and beverages while using khat. Khat use was more frequent in concurrent users
relative to khat-only users. Earlier age of onset of khat use was associated with
greater number of cigarettes smoked during a typical khat session. Approximately
70% of concurrent users reported initiating khat use prior to tobacco use.
Conclusions/Importance: The results provide support for gender differences in
khat and tobacco use, differences in khat use pattern between concurrent users of
khat and tobacco and khat-only users, and positive associations between khat and
tobacco use.
PMID- 27486992
TI - Salespeople in the Surgical Suite: Relationships between Surgeons and Medical
Device Representatives.
AB - BACKGROUND: Industry payments to surgeons have received public attention, but
little is known about the relationships between surgeons and medical device
representatives. Medical device representatives ("device reps") have become an
integral part of operating room personnel. The effect of their presence on
patient care deserves discussion. STUDY DESIGN: We conducted a qualitative,
ethnographic study to explore relationships between surgeons and medical device
representatives, and characterize industry involvement in the training of
surgeons. We used group and individual open-ended interviews to gain insight into
the beliefs, values, and perspectives of surgeons and device reps. We conducted
two focus groups, one with ear, nose, and throat surgeons, and one with hospital
based attending orthopedic surgeons. We also conducted individual interviews with
three former or current medical device representatives, a director of a surgical
residency program at an academic medical center, and a medical assistant for a
multi-physician orthopedic practice. RESULTS: While surgeons view themselves as
indisputably in charge, device reps work hard to make themselves unobtrusively
indispensable in order to establish and maintain influence, and to imbue the
products they provide with personalized services that foster a surgeon's loyalty
to the reps and their companies. Surgeons view industry-funded training
opportunities as a necessary service. Device reps and some surgeons believe that
reps benefit patient care, by increasing efficiency and mitigating deficiencies
among operating room personnel (including the surgeons themselves). CONCLUSIONS:
Our study raises ethical questions about the reliance of surgeons on device reps
and device companies for education and surgical assistance and practical concerns
regarding existing levels of competence among OR personnel.
PMID- 27486993
TI - Separation of Water from Ultralow Sulfur Diesel Using Novel Polymer Nanofiber
Coated Glass Fiber Media.
AB - Polymer nanofibers with interpenetrating network (IPN) morphology are used in
this work for the development of composite, hydrophobic filter media in
conjunction with glass fibers for removal of water droplets from ultralow sulfur
diesel (ULSD). The nanofibers are produced from hydrophobic polyvinyl acetate
(PVAc) and hydrophilic polyvinylpyrrolidone (PVP) by spinning the polymer
solutions using gas jet fiber (GJF) method. The nanofibers coat the individual
glass fibers due to polar-polar interactions during the spinning process and
render the filter media highly hydrophobic with a water contact angle approaching
150 degrees . The efficiency of the resultant filter media is evaluated in terms
of separation of water droplets of average size 20 MUm from the suspensions in
ULSD.
PMID- 27486994
TI - Guideline Adherence Regarding the Use of Expensive Drugs in Daily Practice: The
Examples of Trastuzumab in Breast Cancer and Bortezomib in Multiple Myeloma.
AB - BACKGROUND: The present study was designed to obtain insights into guideline
adherence regarding the use of expensive drugs in The Netherlands in daily
practice and into the patients' perspective on the decision-making process.
MATERIAL AND METHODS: A retrospective review of medical charts regarding the use
of trastuzumab in early and metastatic breast cancer (EBC/MBC) and bortezomib in
multiple myeloma (MM) was conducted. Prescription according to clinical practice
guidelines was assessed. The review was supplemented with patient interviews.
RESULTS: Of 702 adjuvant-treated EBC patients, 97% had a documented human
epidermal growth factor receptor 2 (HER2) testing (23% HER2 positive). 92%
(147/160) of the HER2-positive EBC patients were treated with trastuzumab. Of 594
MBC patients, 81% had a documented HER2 testing (19% HER2 positive). 82% (75/91)
of the HER2-positive MBC patients were treated with trastuzumab. Of 68 MM
patients, 50% were treated with bortezomib. Reasons not to treat were consistent
with the guidelines. Patients were generally satisfied with the decision-making
process; improvements in patient education were suggested (e.g., repeating the
information given, adding information on side effects). CONCLUSIONS: Guidelines
were generally well followed with respect to trastuzumab and bortezomib,
indicating that funding did not influence the treatment decisions of physicians.
In view of the growing numbers of both cancer patients and expensive new
anticancer drugs, and increasing budget constraints, it is unclear whether the
present-day policies will guarantee a similar level of guideline adherence.
Patient involvement in decision-making could be increased by improving the
patient education on treatment.
PMID- 27486995
TI - Early Cord Metabolite Index and Outcome in Perinatal Asphyxia and Hypoxic
Ischaemic Encephalopathy.
AB - BACKGROUND: A 1H-NMR-derived metabolomic index based on early umbilical cord
blood alterations of succinate, glycerol, 3-hydroxybutyrate and O-phosphocholine
has shown potential for the prediction of hypoxic-ischaemic encephalopathy (HIE)
severity. OBJECTIVE: To evaluate whether this metabolite score can predict 3-year
neurodevelopmental outcome in infants with perinatal asphyxia and HIE, compared
with current standard biochemical and clinical markers. METHODS: From September
2009 to June 2011, infants at risk of perinatal asphyxia were recruited from a
single maternity hospital. Cord blood was drawn and biobanked at delivery.
Neonates were monitored for development of encephalopathy both clinically and
electrographically. Neurodevelopmental outcome was assessed at 36-42 months using
the Bayley Scales of Infant and Toddler Development, ed. III (BSID-III). Death
and cerebral palsy were also considered as abnormal end points. RESULTS: Thirty
one infants had both metabolomic analysis and neurodevelopmental outcome at 36-42
months. No child had a severely abnormal BSID-III result. The metabolite index
significantly correlated with outcome (rho2 = 0.30, p < 0.01), which is robust to
predict both severe outcome (area under the receiver operating characteristic
curve: 0.92, p < 0.01) and intact survival (0.80, p = 0.01). There was no
correlation between the index score and performance in the individual BSID-III
subscales (cognitive, language, motor). CONCLUSIONS: The metabolite index
outperformed other standard biochemical markers at birth for prediction of
outcome at 3 years, but was not superior to EEG or the Sarnat score.
PMID- 27486996
TI - Role of the Electrostatic Interactions in the Stabilization of Ionic Liquid
Crystals: Insights from Coarse-Grained MD Simulations of an Imidazolium Model.
AB - In order to investigate the role of the electrostatic interactions in stabilizing
various phases of ionic liquids, especially smectic ionic liquid crystals, we
have employed a coarse-grained model of 1-hexadecyl-3-methylimidazolium nitrate,
[C16mim][NO3], to perform molecular dynamics simulations with the partial charges
artificially rescaled by a factor from 0.7 to 1.2. The simulated systems have
been characterized by means of orientational and translational order parameters
and by distribution functions. We have found that increasing the total charge of
the ions strongly stabilizes the ionic smectic phase by shifting the clearing
point (melting into the isotropic liquid phase) to higher temperatures, while a
smaller effect is observed on the stability of the crystal phase. Our results
highlight the importance of the electrostatic interactions in promoting the
formation of ionic liquid crystals through microphase segregation. Moreover, as
the total charge of the model is increased, we observe a transformation from a
homogeneous to a nanosegregated isotropic structure typical of ionic liquids.
Therefore, a connection can be established between the degree of nanosegregation
of ILs and the stability of ILC phases. All the above can be understood by the
competition among electrostatic interactions between charged groups (cationic
head groups and anions), van der Waals interactions between nonpolar cationic
tail groups, and thermal fluctuations.
PMID- 27486997
TI - Diversity of Bacterial Urine and Prostate Gland Tissue Cultures in Patients
Undergoing Transurethral Prostate Gland Resection.
AB - INTRODUCTION: The objective of this study was to identify the types of bacterial
colonization of the prostate gland tissue and urine pre- and postoperatively in
patients undergoing a transurethral resection (TUR) of the prostate gland. In
addition, clinical symptoms and histopathological findings were included.
MATERIAL AND METHODS: Forty three patients were investigated. Urine test strips
and urine cultures were taken pre- and postoperatively and intraoperatively
prostate resection chips were taken for culture. RESULTS: A positive bacterial
culture was found in 20 of 43 (46.5%) patients. Preoperatively, a positive
bacterial culture was found in 12 patients and postoperatively in 7 patients.
Thirteen patients showed a positive culture of the prostate gland tissue. No
patient showed the same bacterial isolates in all 3 samples.
Postinterventionally, 6 patients of the group with positive bacterial cultures
developed complications. From the group of patients without bacterial growth,
only one patient developed a postoperative complication. CONCLUSION: The
bacterial colonization in the 3 different cultures showed an inhomogeneous
spectrum of bacteria without a reproducible pattern. Nevertheless, it clearly
demonstrates that the group with a positive culture is at great risk to develop
postoperative complications.
PMID- 27486998
TI - Intracellular Availability of pDNA and mRNA after Transfection: A Comparative
Study among Polyplexes, Lipoplexes, and Lipopolyplexes.
AB - Intracellular availability of nucleic acids from synthetic vectors is critical
and directly influences the transfection efficiency (TE). Herein, we evaluated
the TE of polymer- and lipid-based nanoplexes (polyplexes, lipoplexes and
lipopolyplexes) of EGFP-encoding mRNA and pDNA. To determine the translation and
transcription efficiency of each nucleic acid nanoplex, in vitro expression was
measured in HEK293T7 cells that permit gene expression in the cytoplasmic region.
Globally, mRNA transfection profile was well corroborative with cytoplasmic
transfection of pT7-pDNA as well as with nuclear transfection of pCMV-DNA.
Irrespective of the nucleic acid, high TE was observed with histidinylated l
polyethylenimine (His-lPEI) polyplexes and dioleyl succinyl paromomycin/O,O
dioleyl-N-histamine phosphoramidate (DOPS/MM27) lipoplexes. Moreover, His-lPEI
polyplexes yielded higher in vitro expression of EGFP for pDNA than for mRNA.
Furthermore, a significant enhancement in the TE in the presence of an excess of
His-lPEI was observed indicating that this polymer promotes cytosolic delivery.
Compared to other nanoplexes, His-lPEI polyplex showed high intracellular
availability of DNA and mRNA along with low cytotoxicity, owing to its rapid
(complete or partial) unpacking in the cytosol and/or endosomes. This study gives
an insight that, whether with mRNA or pDNA, enhancing nanoplex unpacking in the
endosomes and cytosol would improve the delivery of nucleic acid in the cytosol
and particularly in the case of pDNA where a sufficient available amount of pDNA
in the cytoplasm would definitely improve its transport toward the nucleus.
PMID- 27486999
TI - Correction: Detecting Causality by Combined Use of Multiple Methods: Climate and
Brain Examples.
AB - [This corrects the article DOI: 10.1371/journal.pone.0158572.].
PMID- 27487000
TI - The Use of Cognitive Cues for Anticipatory Strategies in a Dynamic Postural
Control Task - Validation of a Novel Approach to Dual-Task Testing.
AB - INTRODUCTION: Dual-task testing is relevant in the assessment of postural
control. A combination of a primary (motor) and a secondary (distracting
cognitive) tasks is most often used. It remains a challenge however, to
standardize and monitor the cognitive task. In this study a new dual-task testing
approach with a facilitating, rather than distracting, cognitive component was
evaluated. METHODS: Thirty-one community-dwelling elderly and fifteen young
people were tested with respect to their ability to use anticipatory postural
control strategies. The motor task consisted of twenty-five repetitive tasks in
which the participants needed to exceed their limit of stability in order to
touch one out of eight lights. The participants performed three tests. In two of
the tests the color cues of the lights allowed the participants to utilize
cognitive strategies to plan their next movement and improve their performance
time. RESULTS: The young performed the baseline motor task test in an average of
29 seconds, while the average time for the elderly was 44 seconds. When comparing
the performance time with a leading cue to the time with no cue, the young group
improved their performance time significantly better than the elderly did: young:
17% (5), elderly: 5% (8); p<0.001. Similar differences were seen with a more
complicated leading cue: young: 12% (5), elderly: 4% (9); p<0.01. The reliability
of the test showed moderate to substantial agreement (ICC = 0.74), with a small
learning effect between two sessions. CONCLUSION: The dual-task test was
sensitive enough to discriminate between elderly and young people. It revealed
that the elderly did not utilize cognitive cues for their anticipatory postural
control strategies as well as the young were able to. The test procedure was
feasible and comprehensible for the participants, and it may be relevant to
standardize a similar test for an alternative dual-task approach in the clinical
setting.
PMID- 27487001
TI - Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe
Leptospirosis: A Prospective Study.
AB - BACKGROUND: Leptospirosis is a health problem worldwide. Its most severe form is
a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS)
and acute kidney injury (AKI), with associated mortality that remains
unacceptably high. We previously demonstrated that early initiation of sustained
low-efficiency dialysis (SLED) followed by daily SLED significantly decreases
mortality. However, the mode of clearance can also affect dialysis patient
outcomes. Therefore, the objective of this study was to compare the effects of
SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with
convective clearance, via hemodiafiltration (SLEDf), in patients with severe
leptospirosis. METHODS: In this prospective study, conducted in the intensive
care unit (ICU) from 2009 through 2012, we compared two groups-SLED (n = 19) and
SLEDf (n = 20)-evaluating demographic, clinical, and biochemical parameters, as
well as serum levels of interleukins, up to the third day after admission. All
patients received dialysis early and daily thereafter. RESULTS: During the study
period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis;
39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on
mechanical ventilation and were comparable in terms of respiratory parameters.
Mortality did not differ between the SLEDf and SLED groups. However, post
admission decreases in the serum levels of interleukin (IL)-17, IL-7, and
monocyte chemoattractant protein-1 were significantly greater in the SLEDf group.
Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen
ratio were significantly higher in the SLED group. We identified the following
risk factors (sensitivities/specificities) for mortality in severe leptospirosis:
age >= 55 years (67%/91%); serum urea >= 204 mg/dl (100%/70%); creatinine >= 5.2
mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score >= 39.5
(67%/88%); Sequential Organ Failure Assessment score >= 20.5 (67%/85%); and
inspiratory pressure >= 31 mmHg (84%/85%). CONCLUSIONS: The mode of dialysis
clearance might not affect outcomes in severe leptospirosis.
PMID- 27487002
TI - Association between X-Ray Repair Cross-Complementing Group 1 Arg399Gln
Polymorphism and Cervical Cancer Risk: A Meta-Analysis in the Chinese Population.
AB - BACKGROUND: Many studies have examined the association of X-ray repair cross
complementing group 1 (XRCC1) Arg399Gln polymorphism with cervical cancer
susceptibility. However, the results of these studies are inconsistent. To
further assess the effects of XRCC1 Arg399Gln polymorphism on the risk of
cervical cancer in the Chinese population, a meta-analysis was performed.
METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid,
Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge
Infrastructure, and Chinese Biology Medicine through December 2015. Pooled ORs
and 95% CIs were used to assess the strength of the associations. RESULTS: This
meta-analysis identified 7 studies, including 1,589 cases and 2,235 controls. In
the total analyses, a significantly elevated risk of cervical cancer was
associated with variants of XRCC1 Arg399Gln (GA vs. GG: OR 1.30, 95% CI 1.13
1.49; AA + GA vs. GG: OR 1.27, 95% CI 1.02-1.58). In the subgroup analyses
stratified by geographic areas and histopathology type, it revealed the
significant result in South China. CONCLUSIONS: This meta-analysis showed that
the XRCC1 Arg399Gln GA variant might be risk alleles for cervical cancer
susceptibility in the Chinese population, and further studies in other ethnic
groups are required to arrive at definite conclusions.
PMID- 27487003
TI - The Effect of Background Music in Shark Documentaries on Viewers' Perceptions of
Sharks.
AB - Despite the ongoing need for shark conservation and management, prevailing
negative sentiments marginalize these animals and legitimize permissive
exploitation. These negative attitudes arise from an instinctive, yet exaggerated
fear, which is validated and reinforced by disproportionate and sensationalistic
news coverage of shark 'attacks' and by highlighting shark-on-human violence in
popular movies and documentaries. In this study, we investigate another subtler,
yet powerful factor that contributes to this fear: the ominous background music
that often accompanies shark footage in documentaries. Using three experiments,
we show that participants rated sharks more negatively and less positively after
viewing a 60-second video clip of swimming sharks set to ominous background
music, compared to participants who watched the same video clip set to uplifting
background music, or silence. This finding was not an artifact of soundtrack
alone because attitudes toward sharks did not differ among participants assigned
to audio-only control treatments. This is the first study to demonstrate
empirically that the connotative attributes of background music accompanying
shark footage affect viewers' attitudes toward sharks. Given that nature
documentaries are often regarded as objective and authoritative sources of
information, it is critical that documentary filmmakers and viewers are aware of
how the soundtrack can affect the interpretation of the educational content.
PMID- 27487004
TI - Selective Serotonin Reuptake Inhibitors Decrease Pancreatic Insulin Secretion in
Older Adults and Increase the Risk of Insulin Dependence in Type 2 Diabetes
Patients.
AB - OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) may decrease insulin
secretion, but evidence from population studies is scarce. We investigated the
association between SSRIs and markers for glucose-insulin homeostasis in a
nondiabetic older population. Furthermore, we studied the association between
SSRI use and insulin dependence in a diabetic population of older adults.
METHODS: This study was embedded in the prospective population-based Rotterdam
Study cohort (1991-2012). In nondiabetic participants, fasting glucose and
insulin levels and the homeostasis model assessment for insulin sensitivity and
secretion were compared between participants using SSRIs and participants using
no antidepressant. In diabetic patients using oral glucose-lowering agents, the
risk of insulin dependence, defined as the start of insulin treatment, was
compared between participants using SSRIs and participants using no
antidepressant. RESULTS: In nondiabetic participants, SSRI users (n = 87) had,
compared with participants using no antidepressants (n = 5,505), a significantly
(P < .05) lower level of insulin (8.8 mU/L and 9.9 mU/L, respectively), a lower
degree of insulin resistance (2.2% and 2.4%, respectively), and less insulin
secretion (89.1% and 100.4%, respectively), but a similar glucose level.
Furthermore, > 90 days of consecutive use of SSRIs in diabetic patients was
associated with a 2.17 times higher risk (95% confidence interval, 1.02-4.60) of
starting insulin treatment than that of participants using no antidepressants.
CONCLUSIONS: Use of SSRIs was associated with lower insulin secretion in
nondiabetic participants and an increased risk of insulin dependence in type 2
diabetics in older adults. However, additional studies are required to confirm
our results.
PMID- 27487005
TI - Mathematical modelling as a tool to assessment of loads in volleyball player's
shoulder joint during spike.
AB - This article deals with kinematic and kinetic conditions in volleyball attack and
identifies loads in the shoulder joint. Joint angles and velocities of individual
segments of upper limb were measured with the use of the motion capture system
XSENS. Muscle forces and loads in skeletal system were calculated by means of
mathematical model elaborated in AnyBody system. Spikes performed by players in
the best and worst way were compared with each other. The relationships were
found between reactions in shoulder joint and flexion/extension,
abduction/adduction and rotation angles in the same joint and flexion/extension
in the elbow joint. Reactions in shoulder joint varied from 591 N to 2001 N (in
relation to body weight [BW] 83-328%). The analysis proved that hand velocity at
the moment of the ball hit (which varied between 6.8 and 13.3 m s-1) influences
on the value of reaction in joints, but positions of individual segments relative
to each other are also crucial. It was also proved in objective way, that
position of the upper limb during spike can be more or less harmful assuming that
bigger reaction increases possibility of injury, what can be an indication for
trainers and physiotherapists how to improve injury prevention.
PMID- 27487006
TI - Changes in Disparity in County-Level Diagnosed Diabetes Prevalence and Incidence
in the United States, between 2004 and 2012.
AB - BACKGROUND: In recent decades, the United States experienced increasing
prevalence and incidence of diabetes, accompanied by large disparities in county
level diabetes prevalence and incidence. However, whether these disparities are
widening, narrowing, or staying the same has not been studied. We examined
changes in disparity among U.S. counties in diagnosed diabetes prevalence and
incidence between 2004 and 2012. METHODS: We used 2004 and 2012 county-level
diabetes (type 1 and type 2) prevalence and incidence data, along with
demographic, socio-economic, and risk factor data from various sources. To
determine whether disparities widened or narrowed over the time period, we used a
regression-based beta-convergence approach, accounting for spatial
autocorrelation. We calculated diabetes prevalence/incidence percentage point
(ppt) changes between 2004 and 2012 and modeled these changes as a function of
baseline diabetes prevalence/incidence in 2004. Covariates included county-level
demographic and, socio-economic data, and known type 2 diabetes risk factors
(obesity and leisure-time physical inactivity). RESULTS: For each county-level
ppt increase in diabetes prevalence in 2004 there was an annual average increase
of 0.02 ppt (p<0.001) in diabetes prevalence between 2004 and 2012, indicating a
widening of disparities. However, after accounting for covariates, diabetes
prevalence decreased by an annual average of 0.04 ppt (p<0.001). In contrast,
changes in diabetes incidence decreased by an average of 0.04 ppt (unadjusted)
and 0.09 ppt (adjusted) for each ppt increase in diabetes incidence in 2004,
indicating a narrowing of county-level disparities. CONCLUSIONS: County-level
disparities in diagnosed diabetes prevalence in the United States widened between
2004 and 2012, while disparities in incidence narrowed. Accounting for
demographic and, socio-economic characteristics and risk factors for type 2
diabetes narrowed the disparities, suggesting that these factors are strongly
associated with changes in disparities. Public health interventions that target
modifiable risk factors, such as obesity and physical inactivity, in high burden
counties might further reduce disparities in incidence and, over time, in
prevalence.
PMID- 27487007
TI - High-Throughput, Automated Protein A Purification Platform with Multiattribute LC
MS Analysis for Advanced Cell Culture Process Monitoring.
AB - The levels of many product related variants observed during the production of
monoclonal antibodies are dependent on control of the manufacturing process,
especially the cell culture process. However, it is difficult to characterize
samples pulled from the bioreactor due to the low levels of product during the
early stages of the process and the high levels of interfering reagents.
Furthermore, analytical results are often not available for several days, which
slows the process development cycle and prevents "real time" adjustments to the
manufacturing process. To reduce the delay and enhance our ability to achieve
quality targets, we have developed a low-volume, high-throughput, and high
content analytical platform for at-line product quality analysis. This workflow
includes an automated, 96-well plate protein A purification step to isolate
antibody product from the cell culture fermentation broth, followed by rapid,
multiattribute LC-MS analysis. We have demonstrated quantitative correlations
between particular process parameters with the levels of glycosylated and
glycated species in a series of small scale experiments, but the platform could
be used to monitor other attributes and applied across the biopharmaceutical
industry.
PMID- 27487008
TI - Synthesis of C60-Fused Tetrahydrocarbazole/Dibenzothiophene/Benzothiophene and
Dibenzofuran Derivatives via Metal-Free Oxidative Dehydrogenative
Carboannulation.
AB - A transition-metal-free oxidative dehydrogenative coupling reaction has been
developed for the direct construction of novel C60-fused tetrahydrocarbazoles,
dibenzothiophenes, benzothiophenes, and dibenzofurans. This new carboannulation
reaction features high atom economy, operational simplicity, broad substrate
scope, and excellent functional-group tolerance and provides a convenient access
to a scarce class of fullerene derivatives.
PMID- 27487009
TI - Oral Health Status Is Associated with Common Medical Comorbidities in Older
Hospital Inpatients.
AB - OBJECTIVES: To investigate oral health status and abnormalities in older adults
admitted acutely to the hospital and explore the association with common medical
comorbidities. DESIGN: Cross-sectional study. SETTING: Hospital. PARTICIPANTS:
All individuals aged 70 and older (mean age 84.4, 61.4% female) admitted to a
geriatric service over 3 months (N = 202). MEASUREMENTS: In-person assessment
using the Oral Health Assessment Tool (OHAT) (range 0-2, 2 = poorest) for lips,
tongue, gums and soft tissue, saliva, teeth, dentures, oral cleanliness, and
dental pain. Comorbidities and medications were also recorded. RESULTS: One
hundred twenty-eight (63%) participants had full or partial dentures, and 31
(15%) were edentulous. Median OHAT score was 6 (interquartile range 5-8). Of the
eight domains, saliva scored worst, with 53% scoring 2. On univariate analysis,
the highest (poorest) tertile of OHAT (score >=8) was associated with dementia
(odds ratio (OR) = 2.41, 95% confidence interval (CI) = 1.13-5.12, P = .02),
moderate to severe renal impairment (estimated glomerular filtration rate <30
mL/min per 1.73 m(2) at discharge) (OR = 5.52, 95% CI = 1.54-19.69, P = .009),
recent anticholinergic medication burden (P = .02), and low oral pH (P = .05). On
multivariate analysis adjusted for oral pH and anticholinergic medication burden,
dementia (OR = 2.29, P = .02) and moderate to severe renal impairment (OR = 5.64,
P = .01) were independently associated with the highest tertile of OHAT. Charlson
Comorbidity Index (includes renal disease, dementia) was associated with OHAT on
univariate analysis (Spearman rho = 0.19, P = .01) but not when adjusted for oral
pH (P = .10). CONCLUSION: Poorer oral health was not uncommon and was associated
with dementia and renal impairment even after adjustment for anticholinergic
medication and oral pH. Oral health screening should be considered for vulnerable
populations.
PMID- 27487010
TI - Decomposition nitrogen is better retained than simulated deposition from mineral
amendments in a temperate forest.
AB - Nitrogen (N) deposition (NDEP ) drives forest carbon (C) sequestration but the
size of this effect is still uncertain. In the field, an estimate of these
effects can be obtained by applying mineral N fertilizers over the soil or forest
canopy. A 15 N label in the fertilizer can be then used to trace the movement of
the added N into ecosystem pools and deduce a C effect. However, N recycling via
litter decomposition provides most of the nutrition for trees, even under heavy
NDEP inputs. If this recycled litter nitrogen is retained in ecosystem pools
differently to added mineral N, then estimates of the effects of NDEP on the
relative change in C (?C/?N) based on short-term isotope-labelled mineral
fertilizer additions should be questioned. We used 15 N labelled litter to track
decomposed N in the soil system (litter, soils, microbes, and roots) over 18
months in a Sitka spruce plantation and directly compared the fate of this 15 N
to an equivalent amount in simulated NDEP treatments. By the end of the
experiment, three times as much 15 N was retained in the O and A soil layers when
N was derived from litter decomposition than from mineral N additions (60% and
20%, respectively), primarily because of increased recovery in the O layer. Roots
expressed slightly more 15 N tracer from litter decomposition than from simulated
mineral NDEP (7.5% and 4.5%) and compared to soil recovery, expressed
proportionally more 15 N in the A layer than the O layer, potentially indicating
uptake of organic N from decomposition. These results suggest effects of NDEP on
forest ?C/?N may not be apparent from mineral 15 N tracer experiments alone.
Given the importance of N recycling, an important but underestimated effect of
NDEP is its influence on the rate of N release from litter.
PMID- 27487011
TI - Surface-Based fMRI-Driven Diffusion Tractography in the Presence of Significant
Brain Pathology: A Study Linking Structure and Function in Cerebral Palsy.
AB - Diffusion MRI (dMRI) tractography analyses are difficult to perform in the
presence of brain pathology. Automated methods that rely on cortical parcellation
for structural connectivity studies often fail, while manually defining regions
is extremely time consuming and can introduce human error. Both methods also make
assumptions about structure-function relationships that may not hold after
cortical reorganisation. Seeding tractography with functional-MRI (fMRI)
activation is an emerging method that reduces these confounds, but inherent
smoothing of fMRI signal may result in the inclusion of irrelevant pathways. This
paper describes a novel fMRI-seeded dMRI-analysis pipeline based on surface
meshes that reduces these issues and utilises machine-learning to generate task
specific white matter pathways, minimising the requirement for manually-drawn
ROIs. We directly compared this new strategy to a standard voxelwise fMRI-dMRI
approach, by investigating correlations between clinical scores and dMRI metrics
of thalamocortical and corticomotor tracts in 31 children with unilateral
cerebral palsy. The surface-based approach successfully processed more
participants (87%) than the voxel-based approach (65%), and provided
significantly more-coherent tractography. Significant correlations between dMRI
metrics and five clinical scores of function were found for the more superior
regions of these tracts. These significant correlations were stronger and more
frequently found with the surface-based method (15/20 investigated were
significant; R2 = 0.43-0.73) than the voxelwise analysis (2 sig. correlations;
0.38 & 0.49). More restricted fMRI signal, better-constrained tractography, and
the novel track-classification method all appeared to contribute toward these
differences.
PMID- 27487012
TI - Ozone mediators effect on "in vitro" scratch wound closure.
AB - The beneficial effect of low doses of ozone on wound healing has been well
documented and attributed mainly to its bactericidal and pro-oxidant properties.
Because ozone itself does not penetrate the cells but immediately reacts with
polyunsaturated fatty acids, its effects are the results of oxidative mediators.
Among the molecule produces by the interaction of ozone with biological systems,
there are HNE and H2O2. At today, the cellular mechanisms accounting for the
positive effects of mild ozonization on wound closure are still largely
unexplored. The aim of the present study was to evaluate the effect of different
non-toxic doses of ozonated saline ranging from 2 to 300 MUM, in an in vitro
wound scratch model by the use of human keratinocytes. The results showed that
ozonated saline is able to improve in vitro wound healing by stimulating cell
proliferation as measured by BrdU assay and PCNA protein levels. In order to
better elucidate the molecules that play the main role in the beneficial effect
of ozonated saline in wound healing, HNE and H2O2 were used alone or in
combination to mimic ozonated saline effect. Surprisingly, keratinocytes treated
with different doses of HNE and H2O2 did not significantly improve the wound
closure, while the combination of the two compounds was able to improve wound
closure. In addition, Nrf2 pathways were also activated as determined by its
translocation to the nucleus and the increased HO1 gene expression. The present
work suggests that ozonated saline effect on wound closure is the results of the
combination of more molecules among which HNE and H2O2 play a key role.
PMID- 27487013
TI - Contemporary methodological issues in drug development: the functionality of
blinding is poorly studied.
AB - Blinding is an important methodological principle in drug development. This
article reviews the functionality of blinding within the context of bias
minimizing structures of randomized clinical trials. Blinding is not well
understood and not well studied. The risk of bias domain 'blinding' is commonly
assumed to be 'low-risk' whenever readers come across randomized clinical trials
labeled as 'blinded'. However, empirical evidence has shown that this assumption
cannot be taken for granted. The functionality of blinding techniques in
preventing bias requires further studies.
PMID- 27487014
TI - High temperature homogenization improves impact toughness of vitamin E-diffused,
irradiated UHMWPE.
AB - Diffusion of vitamin E into radiation cross-linked ultrahigh molecular weight
polyethylene (UHMWPE) is used to increase stability against oxidation of total
joint implant components. The dispersion of vitamin E throughout implant preforms
has been optimized by a two-step process of doping and homogenization. Both of
these steps are performed below the peak melting point of the cross-linked
polymer (<140 degrees C) to avoid loss of crystallinity and strength. Recently,
it was discovered that the exposure of UHMWPE to elevated temperatures, around
300 degrees C, for a limited amount of time in nitrogen, could improve the
toughness without sacrificing wear resistance. We hypothesized that high
temperature homogenization of antioxidant-doped, radiation cross-linked UHMWPE
could improve its toughness. We found that homogenization at 300 degrees C for 8
h resulted in an increase in the impact toughness (74 kJ/m2 compared to 67 kJ/m2
), the ultimate tensile strength (50 MPa compared to 43 MPa) and elongation at
break (271% compared to 236%). The high temperature treatment did not compromise
the wear resistance or the oxidative stability as measured by oxidation induction
time. In addition, the desired homogeneity was achieved at a much shorter
duration (8 h compared to >240 h) by using high temperature homogenization. (c)
2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
Res 35:1343-1347, 2017.
PMID- 27487015
TI - All-Trans Retinoic Acid-Induced Craniofacial Malformation Model: A Prenatal and
Postnatal Morphological Analysis.
AB - OBJECTIVE: To characterize the prenatal and postnatal craniofacial bone
development in mouse model of all-trans retinoic acid (ATRA) exposure at
different ages by a quantitative and morphological analysis of skull morphology.
METHODS: Pregnant mice were exposed to ATRA at embryonic day 10 (E10) and 13
(E13) by oral gavage. Skulls of mice embryos at E19.5 and adult mice at postnatal
day 35 (P35) were collected for high-resolution microcomputed tomography
(microCT) imaging scanning and section HE staining. Reconstruction and
measurement of mouse skulls were performed for prenatal and postnatal analysis of
the control and ATRA-exposed mice. RESULTS: Craniofacial malformations in mouse
models caused by ATRA exposure were age dependent. ATRA exposure at E10 induced
cleft palate in 81.8% of the fetuses, whereas the palatine bone of E13-exposed
mice was intact. Inhibitions of maxilla and mandible development with
craniofacial asymmetry induced were observed at E19.5 and P35. Compared with
control and E13-exposed mice, the palatine bones of E10-exposed mice were not
elevated and were smaller in dimension. Some E10-exposed mice exhibited other
craniofacial abnormalities, including premature fusion of mandibular symphysis
with a missing mandibular incisor and a smaller mandible. Severe deviated snouts
and amorphous craniofacial suture were detected in E13-exposed mice at P35.
CONCLUSION: These morphological variations in E10- and E13-exposed mice suggested
that ATRA was teratogenic in craniofacial bone development in mice and the effect
was age dependent.
PMID- 27487016
TI - Incidence and Mortality of Solid Cancers in People Exposed In Utero to Ionizing
Radiation: Pooled Analyses of Two Cohorts from the Southern Urals, Russia.
AB - BACKGROUND: Previous studies have shown that acute external in utero exposure to
ionizing radiation can increase cancer risk. It is not known whether chronic
exposure at low dose rates, including due to radionuclide intake, influences the
lifetime risk of solid cancers in the offspring. The objective of this study was
to investigate solid cancer risk after in utero irradiation. METHODS: Cancer
incidence and mortality over a 60-year period (from January 1950 to December
2009) were analyzed in the Urals Prenatally Exposed Cohort (UPEC). The cohort
comprised in utero exposed offspring of Mayak Production Association female
workers and of female residents of Techa River villages. Some of the offspring
also received postnatal exposure, either due to becoming radiation workers
themselves or due to continuing to live in the contaminated areas of the Techa
River. The mortality analyses comprised 16,821 subjects (601,372 person-years),
and the incidence analyses comprised 15,813 subjects (554,411 person-years).
Poisson regression was used to quantify the relative risk as a function of the in
utero soft tissue dose (with cumulative doses up to 944.9 mGy, mean dose of 14.1
mGy in the pooled cohort) and the postnatal stomach dose for solid cancer
incidence and mortality. RESULTS: When a log-linear model was used, relative risk
of cancer per 10 mGy of in utero dose was 0.99 (95% confidence interval (CI) =
0.96 to 1.01) based on incidence data and 0.98 (CI = 0.94 to 1.01) based on
mortality data. Postnatal exposure to ionizing radiation was positively
associated with the solid cancer risk in members of the UPEC, with a relative
risk of 1.02 per 10mGy CI = 1.00 to 1.04). CONCLUSIONS: No strong evidence was
found that chronic low-dose-rate exposure of the embryo and fetus increased the
risk of solid cancers in childhood or in adulthood. For both incidence and
mortality, a tendency towards a decreased relative risk was noted with increasing
doses to soft tissues of the fetus. Further follow-up will provide more precise
radiation risk estimates of solid cancer as cohort members are approaching their
60s and cancer becomes more common.
PMID- 27487017
TI - Polyglandular endocrinopathy type II (Schmidt's syndrome) in a Dobermann
pinscher.
AB - A three-year-old, female neutered, Dobermann pinscher was presented for
investigation of lethargy, episodic collapse, ataxia and myxoedema. Primary
hypothyroidism and primary cortisol-deficient hypoadrenocorticism were diagnosed
based on history, physical examination and compatible hormonal analysis.
Increased serum concentrations of thyroglobulin autoantibodies and 21-hydroxylase
autoantibodies indicated an immune-mediated aetiology. The case was complicated
by lymphadenopathy with hand-mirror lymphocytes, classically identified in
lymphoma. A polymerase chain reaction test for antigen receptor rearrangement
indicated polyclonality and therefore reactive lymphadenopathy. The dog's
clinical signs resolved following introduction of levothyroxine and prednisolone.
Prioritising the problem-based approach in this case facilitated the diagnosis of
hypoadrenocorticism in addition to hypothyroidism due to the persistence of
clinical signs despite thyroxine replacement. Importantly, atypical adrenal gland
dysfunction was not misinterpreted as inadequate therapeutic response to
thyroxine supplementation. The observation that polyglandular endocrinopathy type
II can occur in dogs suggests that in dogs with a suboptimal response to
treatment for hypothyroidism or hypoadrenocorticism comorbid endocrinopathies
should be investigated.
PMID- 27487018
TI - Factors Influencing the Timeliness of Emergency Medical Service Response to Time
Critical Emergencies.
AB - OBJECTIVE: While emergency medical service (EMS) response times (ERT) remain a
leading measure of system performance in many developed countries, relatively few
studies have explored the factors associated with meeting benchmark performance
for potentially time critical incidents. The purpose of this study was to
identify system-level and patient-level factors associated with ERT, which are
readily available at the time of ambulance dispatch. METHODS: Between July 2009
and June 2014, we included data from 1,000,458 EMS responses to time critical
"lights and sirens" incidents in Melbourne, Australia. The primary outcome
measure was ERT, defined as the time from emergency call to the arrival of the
first EMS team on scene. Quantile regression models were used to identify system
level and patient-level factors associated with 10-percentile intervals of ERT.
RESULTS: The median ERT was 10.6 minutes (IQR: 8.1-14.0), increasing from 9.6
minutes (IQR: 7.6-12.5) in 2009/10 to 11.0 minutes (IQR: 8.4-14.7) in 2013/14 (p
< 0.001). System-level factors independently associated with the 90th percentile
ERT were distance to scene, activation time, turnout time, case upgrade, hour of
day, day of week, workload in the previous hour, ambulance skill set, priority
zero case (e.g., suspected cardiac or respiratory arrest), and average hospital
delay time in the previous hour. Patient-level factors such as age, gender, chief
medical complaint, and severity of complaint were also significantly associated
with ERT. CONCLUSIONS: System-level and patient-level factors available at the
time of ambulance dispatch are useful predictors of ERT performance, which could
be used to improve the timeliness of EMS response.
PMID- 27487019
TI - Cryptic, Sympatric Diversity in Tegu Lizards of the Tupinambis teguixin Group
(Squamata, Sauria, Teiidae) and the Description of Three New Species.
AB - Tegus of the genera Tupinambis and Salvator are the largest Neotropical lizards
and the most exploited clade of Neotropical reptiles. For three decades more than
34 million tegu skins were in trade, about 1.02 million per year. The genus
Tupinambis is distributed in South America east of the Andes, and currently
contains four recognized species, three of which are found only in Brazil.
However, the type species of the genus, T. teguixin, is known from Bolivia,
Brazil, Colombia, Ecuador, French Guyana, Guyana, Peru, Suriname, Trinidad and
Tobago, and Venezuela (including the Isla de Margarita). Here we present
molecular and morphological evidence that this species is genetically divergent
across its range and identify four distinct clades some of which are sympatric.
The occurrence of cryptic sympatric species undoubtedly exacerbated the
nomenclatural problems of the past. We discuss the species supported by molecular
and morphological evidence and increase the number of species in the genus
Tupinambis to seven. The four members of the T. teguixin group continue to be
confused with Salvator merianae, despite having a distinctly different morphology
and reproductive mode. All members of the genus Tupinambis are CITES Appendix II.
Yet, they continue to be heavily exploited, under studied, and confused in the
minds of the public, conservationists, and scientists.
PMID- 27487020
TI - The Effectiveness of Bacteriophages against Methicillin-Resistant Staphylococcus
aureus ST398 Nasal Colonization in Pigs.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an important colonizer in
animals and an opportunistic pathogen in humans. In humans, MRSA can cause
infections that might be difficult to treat because of antimicrobial resistance.
The use of bacteriophages has been suggested as a potential approach for the
control of MRSA colonization to minimize the-often occupational-exposure of
humans. The aim of this study was to assess the efficacy of bacteriophage
treatment on porcine nasal colonization with MRSA in vitro, in vivo, and ex vivo.
The effectiveness of a bacteriophage combination of phage K*710 and P68 was
assessed in vitro by incubating them with MRSA V0608892/1 (ST398) measuring the
OD600 hourly. To study the in vivo effect, bacteriophages were administered in a
gel developed for human application, which contain 109 plaque-forming units
(pfu)/mL (K and P68 in a 19.25:1 ratio) for 5 days to piglets (N = 8) that were
experimentally colonized with the MRSA strain. Eight piglets experimentally
colonized were used as a negative control. The MRSA strain was also used to
colonize porcine nasal mucosa explants and bacteriophages were applied to assess
the ex vivo efficacy of treatment. Bacteriophages were effective in vitro. In
vivo, sixteen piglets were colonized with MRSA but the number of CFU recovered
after the application of the bacteriophages in 8 piglets was not reduced compared
to the control animals (approx. 105 CFU/swab). In the ex vivo model, 108 CFU were
used to establish colonization with MRSA; a reduction of colonization was not
observed after application of bacteriophages. However, application of mupirocin
both in vivo and ex vivo resulted in a near eradication of MRSA. IN CONCLUSION:
i) The MRSA strain was killed in the presence of the bacteriophages phage K*710
and P68 in vitro. ii) Bacteriophages did not reduce porcine nasal colonization in
vivo or ex vivo. Physiological in vivo and ex vivo conditions may explain these
observations. Efficacy in the ex vivo model matched that of the in vivo system.
PMID- 27487026
TI - A Molecular Rotor that Measures Dynamic Changes of Lipid Bilayer Viscosity Caused
by Oxidative Stress.
AB - Oxidation of cellular structures is typically an undesirable process that can be
a hallmark of certain diseases. On the other hand, photooxidation is a necessary
step of photodynamic therapy (PDT), a cancer treatment causing cell death upon
light irradiation. Here, the effect of photooxidation on the microscopic
viscosity of model lipid bilayers constructed of 1,2-dioleoyl-sn-glycero-3
phosphocholine has been studied. A molecular rotor has been employed that
displays a viscosity-dependent fluorescence lifetime as a quantitative probe of
the bilayer's viscosity. Thus, spatially-resolved viscosity maps of lipid
photooxidation in giant unilamellar vesicles (GUVs) were obtained, testing the
effect of the positioning of the oxidant relative to the rotor in the bilayer. It
was found that PDT has a strong impact on viscoelastic properties of lipid
bilayers, which 'travels' through the bilayer to areas that have not been
irradiated directly. A dramatic difference in viscoelastic properties of oxidized
GUVs by Type I (electron transfer) and Type II (singlet oxygen-based)
photosensitisers was also detected.
PMID- 27487027
TI - Lipid lowering: PCSK9 inhibitors - new kids on the block target their
breakthrough.
PMID- 27487028
TI - Effects of Conjugated Linoleic Acid Associated With Endurance Exercise on Muscle
Fibres and Peroxisome Proliferator-Activated Receptor gamma Coactivator 1 alpha
Isoforms.
AB - Conjugated linoleic acid (CLA) has been reported to improve muscle hypertrophy,
steroidogenesis, physical activity, and endurance capacity in mice, although the
molecular mechanisms of its actions are not completely understood. The aim of the
present study was to identify whether CLA alters the expression of any of the
peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1alpha)
isoforms, and to evaluate the possible existence of fibre-type-specific
hypertrophy in the gastrocnemius and plantaris muscles. Mice were randomly
assigned to one of four groups: placebo sedentary, CLA sedentary, placebo
trained, or CLA trained. The CLA groups were gavaged with 35 MUl per day of
Tonalin(r) FFA 80 food supplement containing CLA throughout the 6-week
experimental period, whereas the placebo groups were gavaged with 35 MUl
sunflower oil each day. Each administered dose of CLA corresponded to
approximately 0.7 g/kg or 0.5%, of the dietary daily intake. Trained groups ran 5
days per week on a Rota-Rod for 6 weeks at increasing speeds and durations. Mice
were sacrificed by cervical dislocation and hind limb posterior muscle groups
were dissected and used for histological and molecular analyses. Endurance
training stimulated mitochondrial biogenesis by PGC1alpha isoforms (tot, alpha1,
alpha2, and alpha3) but CLA supplementation did not stimulate PGC1alpha isoforms
or mitochondrial biogenesis in trained or sedentary mice. In the plantaris
muscle, CLA supplementation induced a fibre-type-specific hypertrophy of type IIx
muscle fibres, which was associated with increased capillary density and was
different from the fibre-type-specific hypertrophy induced by endurance exercise
(of types I and IIb muscle fibres). J. Cell. Physiol. 232: 1086-1094, 2017. (c)
2016 Wiley Periodicals, Inc.
PMID- 27487030
TI - Correction: A Pilot Study Examining Physical and Social Warmth: Higher (Non
Febrile) Oral Temperature Is Associated with Greater Feelings of Social
Connection.
AB - [This corrects the article DOI: 10.1371/journal.pone.0156873.].
PMID- 27487031
TI - Overexpression of AhpC enhances stress tolerance and N2-fixation in Anabaena by
upregulating stress responsive genes.
AB - The study explores the significance of peroxides in regulating the CO2- and N2
fixation capacities in Anabaena sp. PCC7120. To this end Anabaena strains were
generated carrying an extra copy of ahpC (An+ahpC) or by deleting from their
endogenous functional ahpC (AnDeltaahpC). AhpC levels were 2.2- to 6.0-fold
higher in An+ahpC than in wild type. An+ahpC revealed 1.4- to 2-fold upregulation
of photosystems I and II, nitrogenase, superoxide dismutase and catalase
activities while same activities were 1.3- to 2.5-fold downregulated in the
insertional mutant (AnDeltaahpC) compared to the wild type. Peroxide, superoxide
and malondialdehyde contents were low in An+ahpC and high in AnDeltaahpC. Growth
was inhibited in AnDeltaahpC by approximately 40-60% compared to a 33-40%
enhanced growth in An+ahpC under selected stresses. Most interestingly,
heterocyst frequency was increased in An+ahpC. In order to address
transcriptional and posttranscriptional effects, transcripts of genes including
groEL, fld, kat, gor, gst, dps, bfr, tf, sodA, dnaK, prx, uspA, pcs and apx were
quantified and found to be increased 1.33- to 7.70-fold in unstressed and 1.76-
to 13.80-fold in stressed An+ahpC. In a converse manner, they were downregulated
by 1.20- to 7.50-fold in unstressed and 1.23 to 10.20-fold in stressed
AnDeltaahpC. It is concluded that the level of AhpC controls a major set of
metabolic and developmental genes in normal and stress conditions and thus likely
is in the core of the redox regulatory system of Anabaena.
PMID- 27487032
TI - Systems genetics - deciphering the complex disease with a systems approach.
PMID- 27487029
TI - RNAseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation as a Major
Abnormality in ALS Spinal Cord.
AB - ALS is a rapidly progressive, devastating neurodegenerative illness of adults
that produces disabling weakness and spasticity arising from death of lower and
upper motor neurons. No meaningful therapies exist to slow ALS progression, and
molecular insights into pathogenesis and progression are sorely needed. In that
context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to
define gene network abnormalities in RNA samples depleted of rRNA and isolated
from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50
million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied
three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of
differentially expressed genes (DEG's). Ingenuity Pathways Analysis (IPA) and
Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory
processes as significantly elevated in our ALS samples, with tumor necrosis
factor (TNF) found to be a major pathway regulator (IPA) and TNFalpha-induced
protein 2 (TNFAIP2) as a major network "hub" gene (WGCNA). Using the oPOSSUM
algorithm, we analyzed transcription factors (TF) controlling expression of the
nine DEG/hub genes in the ALS samples and identified TF's involved in
inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA
heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2
(also a DEG identified by all three algorithms) reduced cell viability and
induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms
for DEG identification, and an unsupervised gene co-expression network approach,
we identified significant elevation of inflammatory processes in ALS spinal cord
with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in
human motor neurons, the population most vulnerable to die in ALS, increased cell
death and caspase 3/7 activation. We propose that therapies targeted to reduce
inflammatory TNFalpha signaling may be helpful in ALS patients.
PMID- 27487033
TI - Comparison of Sterile vs Nonsterile Gloves in Cutaneous Surgery and Common
Outpatient Dental Procedures: A Systematic Review and Meta-analysis.
AB - IMPORTANCE: Whether the use of sterile vs nonsterile gloves in outpatient
cutaneous procedures affects the rate of postoperative wound infection is
unknown. OBJECTIVE: To explore rates of surgical site infection (SSI) with the
use of sterile vs nonsterile gloves in outpatient cutaneous surgical procedures.
DATA SOURCES: This systematic review and meta-analysis identified studies from
Ovid MEDLINE (1946 to present), Ovid Cochrane Central Register of Controlled
Trials (1991 to present), Ovid EMBASE (1988 to present), EBSCO Cumulative Index
to Nursing and Allied Health Literature (1980 to present), Scopus (1996 to
present), and Web of Science (1975 to present). STUDY SELECTION: Studies with
information on sterile vs nonsterile gloves in outpatient surgical procedures
were retrieved. Only randomized clinical trials and comparative studies were
included for final analysis. DATA EXTRACTION: Data of trial design, surgery
characteristics, and outcomes from published manuscripts and unpublished data
were independently extracted. MAIN OUTCOMES AND MEASURES: Randomized clinical
trials were considered high quality if randomization, allocation concealment,
blinding, and follow-up completeness were appropriate. Relative risk and 95% CIs
were derived for postoperative wound infections. RESULTS: Fourteen articles met
eligibility and inclusion criteria for systematic review; they included 12 275
unique patients who had undergone 12 275 unique outpatient procedures with
sterile or nonsterile gloves and had follow-up regarding SSI. With the exclusion
of 1 single-arm observational study of 1204 patients, 11 071 patients from 13
studies remained in the meta-analysis. Of these, 228 patients were documented as
having postoperative SSI (2.1%), including 107 of 5031 patients in the nonsterile
glove group (2.1%) and 121 of 6040 patients in the sterile glove group (2.0%).
Overall relative risk for SSI with nonsterile glove use was 1.06 (95% CI, 0.81
1.39). CONCLUSIONS AND RELEVANCE: No difference was found in the rate of
postoperative SSI between outpatient surgical procedures performed with sterile
vs nonsterile gloves.
PMID- 27487034
TI - Structure-activity relationships and action mechanisms of collagen-like
antimicrobial peptides.
AB - An antimicrobial triple-helical peptide, R3, was previously obtained from a
collagen-like combinatorial peptide library. In this research, based on structure
activity relationship studies of R3, a more potent peptide, RR4, with increased
positive net charge and charge density relative to R3, was developed. RR4
exhibited antimicrobial activity against both Gram-negative and Gram-positive
bacterial strains, including multidrug-resistant strains. Its action could be
attributed to entry into cells and interactions with intercellular molecules such
as DNA/RNA that inhibited cell division rather than increasing bacterial membrane
permeability. Furthermore, RR4 exhibited remarkable stability in serum and low
cytotoxicity.
PMID- 27487035
TI - Life-Threatening Hemolytic Anemia after Intrapleural Instillation of OK-432 for
Treatment of Congenital Chylothorax.
AB - Recent reports have advocated treatment of congenital chylothorax with chemical
pleurodesis via intrapleural administration of OK-432. Severe complications have
not been reported, but recently we have encountered a life-threatening case of
massive hemolysis after the procedure. The hemoglobin of the infant decreased
from 8.7 to 3.1 g/dl within 48 h, with concomitant severe hyperbilirubinemia (472
MUmol/l) requiring exchange transfusion. Frontline neonatologists should be aware
of this rare but potentially life-threatening adverse reaction. In addition, it
is possible that a longer indwelling time (3.5 vs. 0.5 h) for OK-432 pleurodesis
may alter the therapeutic response.
PMID- 27487036
TI - Transformation of Flame Retardant Tetrabromobisphenol A by Aqueous Chlorine and
the Effect of Humic Acid.
AB - In this work, it was found that the most widely used brominated flame retardant
tetrabromobisphenol A (TBrBPA) could be transformed by free chlorine over a wide
pH range from 5 to 10 with apparent second-order rate constants from 138 to 3210
M(-1).s(-1). A total of eight products, including one quinone-like compound
(i.e., 2,6-dibromoquinone), two dimers, and several simple halogenated phenols
(e.g., 4-(2-hydroxyisopropyl)-2,6-dibromophenol, 2,6-dibromohydroquinone, and
2,4,6-tribromophenol), were detected by high-performance liquid chromatography
tandem mass spectrometry (HPLC-MS/MS) using a novel precursor ion scan (PIS)
approach. A tentative reaction pathway was proposed: chlorine initially oxidized
TBrBPA leading to the formation of a phenoxy radical, and then this primary
radical and its secondary intermediates (e.g., 2,6-dibromo-4-isopropylphenol
carbocation) formed via beta-scission subsequently underwent substitution,
dimerization, and oxidation reactions. Humic acid (HA) considerably inhibited the
degradation rates of TBrBPA by chlorine even accounting for oxidant consumption.
A similar inhibitory effect of HA was also observed in permanganate and ferrate
oxidation. This inhibitory effect was possibly attributed to the fact that HA
competitively reacted with the phenoxy radical of TBrBPA and reversed it back to
parent TBrBPA. This study confirms that chlorine can transform phenolic compounds
(e.g., TBrBPA) via electron transfer rather than the well-documented
electrophilic substitution, which also have implications on the formation pathway
of halo-benzoquinones during chlorine disinfection. These findings can improve
the understanding of chlorine chemistry in water and wastewater treatment.
PMID- 27487037
TI - Microbes on a Bottle: Substrate, Season and Geography Influence Community
Composition of Microbes Colonizing Marine Plastic Debris.
AB - Plastic debris pervades in our oceans and freshwater systems and the potential
ecosystem-level impacts of this anthropogenic litter require urgent evaluation.
Microbes readily colonize aquatic plastic debris and members of these biofilm
communities are speculated to include pathogenic, toxic, invasive or plastic
degrading-species. The influence of plastic-colonizing microorganisms on the fate
of plastic debris is largely unknown, as is the role of plastic in selecting for
unique microbial communities. This work aimed to characterize microbial biofilm
communities colonizing single-use poly(ethylene terephthalate) (PET) drinking
bottles, determine their plastic-specificity in contrast with seawater and glass
colonizing communities, and identify seasonal and geographical influences on the
communities. A substrate recruitment experiment was established in which PET
bottles were deployed for 5-6 weeks at three stations in the North Sea in three
different seasons. The structure and composition of the PET-colonizing
bacterial/archaeal and eukaryotic communities varied with season and station.
Abundant PET-colonizing taxa belonged to the phylum Bacteroidetes (e.g.
Flavobacteriaceae, Cryomorphaceae, Saprospiraceae-all known to degrade complex
carbon substrates) and diatoms (e.g. Coscinodiscophytina, Bacillariophytina). The
PET-colonizing microbial communities differed significantly from free-living
communities, but from particle-associated (>3 MUm) communities or those
inhabiting glass substrates. These data suggest that microbial community assembly
on plastics is driven by conventional marine biofilm processes, with the plastic
surface serving as raft for attachment, rather than selecting for recruitment of
plastic-specific microbial colonizers. A small proportion of taxa, notably,
members of the Cryomorphaceae and Alcanivoraceae, were significantly discriminant
of PET but not glass surfaces, conjuring the possibility that these groups may
directly interact with the PET substrate. Future research is required to
investigate microscale functional interactions at the plastic surface.
PMID- 27487038
TI - Long-term Recall of Time to Pregnancy.
AB - BACKGROUND: Despite the widespread use of retrospectively reported time to
pregnancy to evaluate fertility either as an outcome or as a risk factor for
chronic disease, only two small studies have directly compared prospective data
with later recall. METHODS: The North Carolina Early Pregnancy Study (1982-1986)
collected prospective time-to-pregnancy data from the beginning of participants'
pregnancy attempt. In 2010, (24-28 years later) women were sent a questionnaire
including lifetime reproductive history that asked about all prior times to
pregnancy. Of the 202 women with prospective time-to-pregnancy data, 76% provided
recalled time to pregnancy. RESULTS: A lower proportion of women with times to
pregnancy >=3 cycles provided a recalled time to pregnancy than women with times
to pregnancy <3 cycles. Also, high gravidity or parity was associated with a
lower likelihood of providing a recalled time to pregnancy. Women with very short
or very long times to pregnancy (1 cycle or >=13 cycles) had good recall of time
to pregnancy. Positive predictive values of 1 or >=13 cycles were 73% and 68%,
respectively, while positive predictive values for other categories of time to
pregnancy ranged from 38% to 58%. The weighted kappa statistic for recalled
versus prospective time to pregnancy was 0.72 (95% confidence interval: 0.65,
0.79). CONCLUSIONS: Recalled time to pregnancy showed good agreement with
prospective time to pregnancy. Informative missingness must be considered when
imputing recalled time to pregnancy. Associations observed in future studies can
be corrected for misclassification.
PMID- 27487039
TI - The Authors Respond: Erratum.
PMID- 27487040
TI - Erratum: A Unification of Mediation and Interaction: A 4-Way Decomposition.
PMID- 27487041
TI - Association between Food Insecurity and Procurement Methods among People Living
with HIV in a High Resource Setting.
AB - OBJECTIVE: People living with HIV in high-resource settings suffer severe levels
of food insecurity; however, limited evidence exists regarding dietary intake and
sub-components that characterize food insecurity (i.e. food quantity, quality,
safety or procurement) in this population. We examined the prevalence and
characteristics of food insecurity among people living with HIV across British
Columbia, Canada. DESIGN: This cross-sectional analysis was conducted within a
national community-based research initiative. METHODS: Food security was measured
using the Health Canada Household Food Security Scale Module. Logistic regression
was used to determine key independent predictors of food insecurity, controlling
for potential confounders. RESULTS: Of 262 participants, 192 (73%) reported food
insecurity. Sub-components associated with food insecurity in bivariate analysis
included: < RDI consumption of protein (p = 0.046); being sick from
spoiled/unsafe food in the past six months (p = 0.010); and procurement of food
using non-traditional methods (p <0.05). In multivariable analyses, factors
significantly associated with food insecurity included: procurement of food using
non-traditional methods [AOR = 11.11, 95% CI: 4.79-25.68, p = <0.001]; younger
age [AOR = 0.92, 95% CI: 0.86-0.96, p = <0.001]; unstable housing [AOR = 4.46,
95% CI: 1.15-17.36, p = 0.031]; household gross annual income [AOR = 4.49, 95%
CI: 1.74-11.60, p = 0.002]; and symptoms of depression [AOR = 2.73, 95% CI: 1.25
5.96, p = 0.012]. CONCLUSIONS: Food insecurity among people living with HIV in
British Columbia is characterized by poor dietary quality and food procurement
methods. Notably, participants who reported procuring in non-traditional manners
were over 10 times more likely to be food insecure. These findings suggest a need
for tailored food security and social support interventions in this setting.
PMID- 27487042
TI - Drug-Induced- or Rheumatic- Valvular Heart Disease in Patients Exposed to
Benfluorex?
AB - There is a risk of misdiagnosis between benfluorex-induced VHD and acute
rheumatic fever (ARF)-related VHD due to common characteristics of both
etiologies. We aimed at estimating the probability for a patient exposed to
benfluorex presenting with VHD to have, at the same time, a history of ARF
related VHD. Such epidemiological approach could help at reducing the risk of
misdiagnosis. We used INSEE data and related literature as well as various
modeling hypotheses to drive and test a formula for calculating the probability
of a patient presenting with VHD and a history of benfluorex intake to have a
prior history of ARF-related VHD. Different scenarios were estimated by a Markov
model on the life course of people born in France between 1940 and 1960.
Sensitivity analyses were performed under these scenarios. According to the
different scenarios and gender, the probability that a patient born between 1940
and 1960 presenting with VHD and a history of benfluorex intake would have had a
prior history of ARF-related VHD varied from 0.2% to 2.7%. The probabilities by
the year of birth were as follows: 0.8%-2.7% for a patient born in 1940, < 0.5%
in all scenarios for patients born after 1955, and < 0.2% in all scenarios for
patients, born in 1960. Our results indicate that the burden of ARF-related VHD
is low in the patient population exposed to benfluorex. The probability of ARF
related VHD should not be over-estimated in the diagnostic procedure of VHD.
PMID- 27487044
TI - Land Use Affects Carbon Sources to the Pelagic Food Web in a Small Boreal Lake.
AB - Small humic forest lakes often have high contributions of methane-derived carbon
in their food webs but little is known about the temporal stability of this
carbon pathway and how it responds to environmental changes on longer time
scales. We reconstructed past variations in the contribution of methanogenic
carbon in the pelagic food web of a small boreal lake in Finland by analyzing the
stable carbon isotopic composition (delta13C values) of chitinous fossils of
planktivorous invertebrates in sediments from the lake. The delta13C values of
zooplankton remains show several marked shifts (approx. 10 0/00), consistent with
changes in the proportional contribution of carbon from methane-oxidizing
bacteria in zooplankton diets. The results indicate that the lake only recently
(1950s) obtained its present state with a high contribution of methanogenic
carbon to the pelagic food web. A comparison with historical and palaeobotanical
evidence indicates that this most recent shift coincided with agricultural land
use changes and forestation of the lake catchment and implies that earlier shifts
may also have been related to changes in forest and land use. Our study
demonstrates the sensitivity of the carbon cycle in small forest lakes to
external forcing and that the effects of past changes in local land use on
lacustrine carbon cycling have to be taken into account when defining
environmental and ecological reference conditions in boreal headwater lakes.
PMID- 27487043
TI - Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive
Sequences in Response to Replication Stress.
AB - The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting
replication recovery under replication stress at genomic regions, yet its precise
role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive
sequences genome-wide in response to hydroxyurea (HU)-induced replication stress.
STN1 deficiency exacerbates the fragility of these sequences under replication
stress, resulting in chromosome fragmentation. We find that upon fork stalling,
CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore,
replication stress induces physical association of CST with RAD51 in an ATR
dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci
formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich
fragile sequences. Collectively, our findings establish that CST promotes RAD51
recruitment to GC-rich repetitive sequences in response to replication stress to
facilitate replication restart, thereby providing insights into the mechanism
underlying genome stability maintenance.
PMID- 27487045
TI - Anti-Zinc Transporter Protein 8 Antibody Testing Is Not Informative in Routine
Prediabetes Screening in Young Patients with Autoimmune Thyroiditis and Celiac
Disease.
AB - BACKGROUND/AIMS: Patients with type 1 diabetes mellitus (T1DM), autoimmune
thyroiditis (ATD), and celiac disease (CD) are at increased risk for developing
other autoimmune diseases. We evaluated zinc transporter 8 (ZnT8) prevalence in
patients with ATD and/or CD in order to define the usefulness of ZnT8
autoantibodies for prediabetes screening. METHODS: Eighty-one young patients with
ATD and/or CD were included in the study; 32 subjects with clinical onset of T1DM
were enrolled as a control group. GAD65, IA-2, and ZnT8 antibodies were measured.
An intravenous glucose tolerance test, C-peptide, glycosylated hemoglobin levels,
and genomic analysis of HLA-DQA1* and -DQB1* were also considered in patients
positive for autoantibodies. RESULTS: The ZnT8 prevalence was higher in T1DM
patients than in patients with other autoimmune diseases (p < 0.001); positive
ZnT8 detection was found in 2 ATD (p = 0.004) and 3 ATD + CD (p = 0.04) patients.
Positive ZnT8 was associated with GAD65 (p = 0.01) but not with IA-2 positivity.
No correlation between ZnT8 detection and the number of T1DM-susceptible HLA-DQ
heterodimers was found. Pathological C-peptide levels and insulin response were
found in subjects with islet autoimmunity and genetic susceptibility. CONCLUSION:
ZnT8 autoantibodies detection in ATD and/or CD patients is low, and routine ZnT8
screening is not justified. ZnT8 evaluation may be recommended in subjects with
autoimmune diseases as a marker for predicting compromised insulin secretion.
PMID- 27487046
TI - The Joint Action of Sesquiterpene Lactones from Leaves as an Explanation for the
Activity of Cynara cardunculus.
AB - The work described herein is a continuation of a previous study centered on the
bioprospect of cardoon (Cynara cardunculus) leaf extracts through the isolation
of secondary metabolites with phytotoxic activity. Chromatographic fractionations
of the ethyl acetate extract and spectroscopic analysis showed that the majority
of the components were sesquiterpene lactones. Of these compounds, aguerin B,
grosheimin, and cynaropicrin were very active on etiolated wheat coleoptile,
standard target species, and weed growth. The joint action of binary mixtures of
these three active sesquiterpene lactones and one nonactive compound (11,13
dihydroxy-8-desoxygrosheimin) was studied. The activities of fixed-ratio mixtures
were assessed on wheat coleoptile. The results can be interpreted with respect to
a reference model by considering dose-response analyses and isobolograms with
linear regression analyses. A total of 17 binary mixtures at different levels of
inhibition (ED25, ED50, and ED75) were studied, and predominantly they responded
additively (25). Deviations from additivity included seven synergistic responses
and two antagonistic responses. The joint action of major sesquiterpene lactones
isolated from C. cardunculus can explain the activities observed in extracts and
fractions. The results reported here reiterate the utility of the wheat
coleoptile bioassay as a quick tool to detect potential synergistic effects in
binary mixtures.
PMID- 27487047
TI - Risk Factors for Parametrial Involvement in Early-Stage Cervical Cancer and
Identification of Patients Suitable for Less Radical Surgery.
AB - BACKGROUND: The aim of this study was to determine risk factors associated with
parametrial involvement (PI) and to identify the subgroup of patients at low risk
for PI. METHODS: The study comprised 565 patients with early-stage cervical
cancer, who underwent radical hysterectomy with pelvic node dissection at
Songklanagarind Hospital between 1987 and 2011. Analysis was performed to
determine factors associated with PI. RESULTS: Overall, 24 (4.25%) women had PI.
PI was more common in patients with non-squamous cell carcinoma, deep stromal
invasion (DSI), tumor size > 2 cm, lymphovascular space invasion (LVSI), and
pelvic node involvement. Multivariate analysis showed that DSI (p < 0.001) and
tumor size > 2 cm (p < 0.001) were independently associated with PI. PI was
linked with decreased recurrence-free (p < 0.001) and overall (p = 0.002)
survival. Of 347 patients with tumor size <= 2 cm and no DSI, only 1 (0.29%) had
PI. CONCLUSION: These findings confirm that PI in early-stage cervical cancer is
uncommon. Risk factors associated with PI were DSI and tumor size > 2 cm. PI is a
predictor of cervical cancer recurrence and decreased survival. Less radical
surgery may be considered in low-risk patients.
PMID- 27487048
TI - Sex Outside the Lines: Authentic Sexuality in a Sexually Dysfunctional Culture.
PMID- 27487049
TI - Treating Out of Control Sexual Behavior: Rethinking Sex Addiction.
PMID- 27487050
TI - Couple Resilience: Emerging Perspectives.
PMID- 27487052
TI - Fostering resilience in the medical community.
PMID- 27487051
TI - Antidepressants in unipolar major depression: what we need to know.
PMID- 27487053
TI - Clinical News.
PMID- 27487054
TI - When deep vein thrombosis occurs in the upper limb.
AB - Upper extremity deep vein thrombosis is a relatively rare condition which has
thus far not attracted much interest in the literature. The differences in its
aetiopathology, different diagnostic modalities and the current standard of care
are discussed in this article.
PMID- 27487055
TI - Female gender and cardiovascular disease.
AB - Despite a generalized belief that women are protected from cardiovascular
disease, this remains the leading cause of death in women. This review focuses on
differences in symptomatology, diagnostic modalities and therapeutic strategies
in women with regard to cardiovascular disease.
PMID- 27487056
TI - Management of atrial fibrillation: when are invasive approaches useful?
AB - The management of atrial fibrillation extends from stroke prevention to rate or
rhythm control strategies. The role of an invasive strategy is expanding and it
remains important to identify suitable candidates early in the disease process.
PMID- 27487057
TI - Smartphone and mobile phone security for the clinician.
AB - Smartphones are near ubiquitous and widely used by doctors in discussing
patients. In all communication doctors should take steps to protect
confidentiality, yet there is a paucity of available information on how
clinicians can bolster cyber security and minimize risk when using their mobile
phone.
PMID- 27487058
TI - Vertical leadership in highly complex and unpredictable health systems.
AB - This article explores how the concept of vertical leadership development might
help health organizations cope with and thrive within highly complex and
unpredictable health systems, looking at concepts of VUCA (volatility,
uncertainty, complexity and ambiguity) and RUPT (rapid, unpredictable,
paradoxical and tangled).
PMID- 27487059
TI - Guidance on feedback of outcome data to improve performance in vascular surgery.
AB - Feedback of performance data is a well-established method of performance
improvement in the health-care setting, although guidance has been limited in the
context of surgical performance. This article outlines how optimal feedback can
be achieved using surgeon outcome data.
PMID- 27487060
TI - Improving the non-technical ward round skills of medical students.
PMID- 27487061
TI - The birth of the antibiotic era.
PMID- 27487062
TI - Tuberculous lymphadenitis in a patient with Good syndrome.
PMID- 27487063
TI - Wrong side oculomotor nerve palsy.
PMID- 27487064
TI - An unusual cause of acute kidney injury.
PMID- 27487066
TI - Errata.
PMID- 27487067
TI - 'Whippits': nitrous oxide gas inhalation as recreational drug use.
PMID- 27487065
TI - Lingual tumour in a 6-year-old boy.
PMID- 27487069
TI - Interscalene vs suprascapular nerve block for shoulder surgery.
PMID- 27487070
TI - Interventional oncology.
PMID- 27487071
TI - Cervical intraepithelial neoplasia: screening and management.
PMID- 27487072
TI - Obstetric complications after treatment of cervical intraepithelial neoplasia.
PMID- 27487073
TI - Nine years of a single referral center management of Stevens-Johnson syndrome and
toxic epidermal necrolysis (Lyell's syndrome).
AB - CONTEXT: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
corresponds to a rare and acute life-threatening mucocutaneous reactions
characterized by extensive necrosis and epidermal detachment. There are no
efficacious pharmaceutical interventions proven through large clinical trials.
OBJECTIVE: We sought to study clinical cases admitted in our institution in order
to determine which drugs and medical comorbidities or treatments impacted the
mortality. MATERIAL AND METHODS: In a retrospective study over 9 years we
evaluated all patients presenting biopsy-proven SJS or TEN for age, gender, total
body surface area involved, causing agents, SCORTEN score, blood transfusion,
steroid administration, intubation, length of intensive care stay and death rate.
Statistical analysis was done using SPSS statistical software. RESULTS: The
highest incidence of SJS and TEN was in age group of 71-80 years. Of the 30
patients, 30% died from SJS/TEN, mainly due sepsis. For each subgroup SJS/TEN
overlap had the highest mortality. The highest mortality was from antibiotic
treatment as causing agent. Step-wise regression analysis identified mechanical
ventilation requirement and age over 65 years as mortality high-risk factors.
DISCUSSION: The most crucial interventions are discontinuation of the offending
drug and prompt referral to a burn unit, which helps in early diagnosis and
decrease mortality in these diseases. CONCLUSION: When SJS/TEN is caused by
antibiotics suspicion of developing fatal sepsis should be high, independently of
patients' medical condition.
PMID- 27487074
TI - Strongly Confined HgTe 2D Nanoplatelets as Narrow Near-Infrared Emitters.
AB - Two-dimensional colloidal nanoplatelets (NPLs), owing to the atomic-level control
of their confined direction (i.e., no inhomogeneous broadening), have
demonstrated improved photoluminescence (PL) line widths for cadmium chalcogenide
based nanocrystals. Here we use cation exchange to synthesize mercury
chalcogenide NPLs. Appropriate control of reaction kinetics enables the 2D
morphology of the NPLs to be maintained during the cation exchange. HgTe and HgSe
NPLs have significantly improved optical features compared to existing materials
with similar band gaps. The PL line width of HgTe NPLs (40 nm full width at half
maximum, centered at 880 nm) is a factor of 2 smaller than typical PbS
nanocrystals (NCs) emitting at the same wavelength. The PL has a lifetime of 50
ns, almost 2 orders of magnitude shorter than small PbS colloidal quantum dots
(CQDs), and a quantum yield of ~10%, almost 2 orders of magnitude shorter than
small PbS colloidal quantum dots (CQDs). These materials are promising for a
large variety of applications spanning from telecommunications to the design of
colloidal topological insulators.
PMID- 27487075
TI - Dose-Dependent Effect of Granulocyte Transfusions in Hematological Patients with
Febrile Neutropenia.
AB - It is still under debate whether granulocyte transfusions (GTs) substantially
increase survival in patients with febrile neutropenia. We retrospectively
examined data relative to 96 patients with hematological malignancies receiving
491 GTs during 114 infectious episodes (IE). Patients were grouped according to
the median doses of granulocytes transfused during the infectious episode (low
dose group: <1.5-x108 cells/Kg; standard-dose group: 1.5-3.0x108 cells/Kg and
high-dose group: >3.0x108 cells/Kg). The impact of clinical, microbiological and
GT-related variables on the infection-related mortality (IRM) was investigated.
The IRM was not influenced by the number of GTs or by the total amount of
granulocytes received, whereas a dose-related effect of the median dose received
for IE was detected at univariate analysis (IRM of 18.4% in the standard-dose
group, 44.4% in the low-dose group and 48.4% in the high-dose group, p = 0.040)
and confirmed at multivariate analysis (OR 3.7, IC 95% 1.5-8.9; 0.004 for
patients not receiving standard doses of GTs). Moreover, patients receiving GTs
at doses lower or greater than standard had increased risk for subsequent ICU
admission and reduced overall survival. The dose-related effect of GTs was
confirmed in bacterial but not in fungal infections. Preliminary findings
obtained from a subgroup of patients candidate to GTs revealed that levels of
inflammatory response mediators increase in a dose-related manner after GTs,
providing a possible explanation for the detrimental effect exerted by high-dose
transfusions. GTs can constitute a valuable tool to improve the outcome of
infections in neutropenic patients, provided that adequate recipient-tailored
doses are supplied. Further investigations of the immunomodulatory effects of GTs
are recommended.
PMID- 27487076
TI - Outer Membrane Vesicles from the Probiotic Escherichia coli Nissle 1917 and the
Commensal ECOR12 Enter Intestinal Epithelial Cells via Clathrin-Dependent
Endocytosis and Elicit Differential Effects on DNA Damage.
AB - Interactions between intestinal microbiota and the human host are complex. The
gut mucosal surface is covered by a mucin layer that prevents bacteria from
accessing the epithelial cells. Thus, the crosstalk between microbiota and the
host mainly rely on secreted factors that can go through the mucus layer and
reach the epithelium. In this context, vesicles released by commensal strains are
seen as key players in signaling processes in the intestinal mucosa. Studies with
Gram-negative pathogens showed that outer membrane vesicles (OMVs) are
internalized into the host cell by endocytosis, but the entry mechanism for
microbiota-derived vesicles is unknown. Escherichia coli strains are found as
part of normal human gut microbiota. In this work, we elucidate the pathway that
mediate internalization of OMVs from the probiotic E.coli Nissle 1917 (EcN) and
the commensal ECOR12 strains in several human intestinal epithelial cell lines.
Time course measurement of fluorescence and microscopy analysis performed with
rhodamine B-R18-labeled OMVs in the presence of endocytosis inhibitors showed
that OMVs from these strains enter epithelial cells via clathrin-mediated
endocytosis. Vesicles use the same endocytosis pathway in polarized epithelial
monolayers. Internalized OMVs are sorted to lysosomal compartments as shown by
their colocalization with clathrin and specific markers of endosomes and
lysosomes. OMVs from both strains did not affect cell viability, but reduce
proliferation of HT-29 cells. Labeling of 8-oxo-dG adducts in DNA revealed that
neither OMVs from EcN nor from ECOR12 promoted oxidative DNA damage. In contrast,
flow cytometry analysis of phosphorylated gammaH2AX evidenced that OMVs from the
probiotic EcN significantly produced more double strand breaks in DNA than ECOR12
OMVs. The EcN genotoxic effects have been attributed to the synthesis of
colibactin. However, it is not known how colibactin is exported and delivered
into host cells. Whether colibactin is secreted via OMVs is an open question that
needs further study.
PMID- 27487077
TI - Examining the Role of Source Credibility and Reference Group Proximity on
Personalized Normative Feedback Interventions for College Student Alcohol Use: A
Randomized Laboratory Experiment.
AB - BACKGROUND: Personalized normative feedback (PNF) interventions are designed to
reduce misperceived drinking norms by delivering feedback regarding the actual
drinking behavior of college students, thereby leading to subsequent reductions
in one's own drinking. OBJECTIVE: We examined the roles of data source
credibility and reference group proximity in the effectiveness of a laboratory
based PNF intervention to reduce perceived drinking norms and thereby decrease
intentions to drink. METHOD: Following completion of an online preintervention
survey and using a 2 (highly credible data source/low credible data source) * 2
(proximal reference group/distal reference group) between-subjects factorial
design, 104 college student drinkers were randomly assigned to condition.
Participants then completed a postintervention questionnaire to assess for
changes in various aspects of drinking. RESULTS: Highly credible feedback was
associated with greater reductions in perceived weekly drinking by American
college students compared to feedback with low credibility. Similarly, more
proximal than distal reference group feedback led to greater reductions in
perceived weekly drinking by a same-gender/same-class year students at one's
university. No condition effects emerged for intended drinks per week.
CONCLUSIONS: PNF interventions may benefit from considering data source
credibility and reference group proximity to reduce misperceptions of college
student drinking, depending on the goals and resources of practitioners
implementing such programs. Even the use of such a distal reference group as
American college students can indeed lead to a reduction of normative perceptions
provided there is an emphasis on the credibility of the data source.
PMID- 27487078
TI - Occupational Risk Factors for COPD: A Case-Control Study.
AB - OBJECTIVES: The aim of this research was to examine the occupational risk factors
for Chronic Obstructive Pulmonary Diseases (COPD) in a range of occupations.
METHODS: Eleven occupations involving different types of exposure were observed
in this multicenter case-control study. Controls and cases were matched for sex,
age and smoking. Multiple logistic regression analyses were used to estimate odds
ratios (ORs). RESULTS: A total of 1,519 participants were initially recruited
between September 2004 and September 2012. After matching, 547 pairs were
obtained. The mean age was 56.3 +/- 10.4 years. Smelter workers were the only
ones with an increased risk of COPD in this study (OR = 7.6, p < 0.0001, 95% CI
[4.5, 12.9]). Physical activity was protective (OR = 0.7), while living in the
city was a risk (OR = 1.6). The main used metals were cast iron, aluminum and
alloys. Molds and cores were mainly made from sand and synthetic resins. Machine
maintenance (65.2%), molding (49.6%), finishing (41.1%) and casting (41.0%) were
the most common activities. Almost all workers (95.1%) cleaned the floors and
machines with a brush or compressed air. CONCLUSIONS: This study demonstrates the
importance of occupational factors in the genesis of COPD, especially among
smelter workers. As with the fight against smoking-related disease, the removal
or substitution of recognized hazardous agents is the best way of preventing the
onset of COPD. This is why it is essential to continue research on its
occupational risk factors.
PMID- 27487080
TI - A Thermodynamic Study of Adenine and Thymine Substitutions in the Loops of the
Oligodeoxyribonucleotide HTel.
AB - Guanine-rich DNA oligodeoxyribonucleotides (ODN) can form four-stranded
structures named quadruplexes (G4s), which are stabilized via the association of
four guanine bases. Quadruplexes have a high level of conformational diversity
depending on the molecularity, sequence, and the cation conditions of the G4
formation. Monomolecular G4 structures have nonguanine loops that usually consist
of between one and four adenine and thymine residues. In the work reported here,
we systematically modified the nucleotides in the loops of the 22 nucleotide ODN,
HTel, which contains four repeats of the human telomeric sequence, GGGTTA. We
studied the effect of different types of bases in the loops on the stability and
topology of the G4s formed. We show that lower steric hindrance of pyrimidine
residues increases the stability of G4s with a major enthalpic contribution.
Stacking of the loop bases onto tetrads could compensate for the loss of
rotational freedom. In addition, in the presence of sodium, the stabilities of
the G4s are loop dependent. In the presence of potassium, the stability of G4
depend on the sequences of each loop. Lastly, in the presence of potassium ions,
the modified HTel ODNs may exist in equilibrium of the two types of the hybrid
topology, and these structures are stabilized by the second loop. Modifications
of the bases in this loop change the topology and stability of the folded
structures.
PMID- 27487079
TI - Co-Evolution of Social Learning and Evolutionary Preparedness in Dangerous
Environments.
AB - Danger is a fundamental aspect of the lives of most animals. Adaptive behavior
therefore requires avoiding actions, objects, and environments associated with
danger. Previous research has shown that humans and non-human animals can avoid
such dangers through two types of behavioral adaptions, (i) genetic preparedness
to avoid certain stimuli or actions, and (ii) social learning. These adaptive
mechanisms reduce the fitness costs associated with danger but still allow
flexible behavior. Despite the empirical prevalence and importance of both these
mechanisms, it is unclear when they evolve and how they interact. We used
evolutionary agent-based simulations, incorporating empirically based learning
mechanisms, to clarify if preparedness and social learning typically both evolve
in dangerous environments, and if these mechanisms generally interact
synergistically or antagonistically. Our simulations showed that preparedness and
social learning often co-evolve because they provide complimentary benefits:
genetic preparedness reduced foraging efficiency, but resulted in a higher rate
of survival in dangerous environments, while social learning generally came to
dominate the population, especially when the environment was stochastic. However,
even in this case, genetic preparedness reliably evolved. Broadly, our results
indicate that the relationship between preparedness and social learning is
important as it can result in trade-offs between behavioral flexibility and
safety, which can lead to seemingly suboptimal behavior if the evolutionary
environment of the organism is not taken into account.
PMID- 27487081
TI - Comparative Proteomic Analysis of Extracellular Vesicles Isolated by Acoustic
Trapping or Differential Centrifugation.
AB - Extracellular vesicles (ECVs), including microparticles and exosomes, are
submicrometer membrane vesicles released by diverse cell types upon activation or
stress. Circulating ECVs are potential reservoirs of disease biomarkers, and the
complexity of these vesicles is significantly lower compared to their source,
blood plasma, which makes ECV-based biomarker studies more promising. Proteomic
profiling of ECVs is important not only to discover new diagnostic or prognostic
markers but also to understand their roles in biological function. In the current
study, we investigated the protein composition of plasma-derived ECVs isolated by
acoustic seed trapping. Additionally, the protein composition of ECVs isolated
with acoustic trapping was compared to that isolated with a conventional
differential centrifugation protocol. Finally, the proteome of ECVs originating
from ST-elevation myocardial infarction patients was compared with that of
healthy controls using label-free LC-MS quantification. The acoustic trapping
platform allows rapid and automated preparation of ECVs from small sample
volumes, which are therefore well-suited for biobank repositories. We found that
the protein composition of trapped ECVs is very similar to that isolated by the
conventional differential centrifugation method.
PMID- 27487082
TI - Quit interest influences smoking cue-reactivity.
AB - Interest in quitting smoking is important to model in cue-reactivity studies,
because the craving elicited by cue exposure likely requires different self
regulation efforts for smokers who are interested in quitting compared to those
without any quit interest. The objective of the current study was to evaluate the
role of quit interest in how cigarette cue exposure influences self-control
efforts. Smokers interested in quitting (n=37) and smokers with no interest in
quitting (n=53) were randomly assigned to a cigarette or neutral cue exposure
task. Following the cue exposure, all participants completed two self-control
tasks, a measure of risky gambling (the Iowa Gambling Task) and a cold pressor
tolerance task. Results indicated that smokers interested in quitting had worse
performance on the gambling task when exposed to a cigarette cue compared to
neutral cue exposure. We also found that people interested in quitting tolerated
the cold pressor task for a shorter amount of time than people not interested in
quitting. Finally, we found that for people interested in quitting, exposure to a
cigarette cue was associated with increased motivation to take steps toward
decreasing use. Overall these results suggest that including quit interest in
studies of cue reactivity is valuable, as quit interest influenced smoking cue
reactivity responses.
PMID- 27487083
TI - Older women, intimate partner violence and mental health: a consideration of the
particular issues for health and healthcare practice.
AB - AIMS AND OBJECTIVES: To explore qualitative evidence in older women with a
history of intimate partner violence and their accounts and experiences of mental
health. BACKGROUND: Intimate partner violence significantly impacts the health
and well-being of women who experience it. However, women who experience intimate
partner violence do not form a homogenous group and the effect on older women has
not been adequately distinguished. While there is a growing body of evidence to
address this deficit, studies to date have tended to concentrate on older women's
experiences of intimate partner violence in totality and as such mental health
issues have been subsumed as a part of the whole. DESIGN: Meta-ethnographic
synthesis of qualitative evidence. METHODS: A systematic search of PUBMED,
Cumulative Index to Nursing and Allied Health Literature, COCHRANE, Medline and
PsycInfo, Sci was completed. The search included articles published up until the
end of December 2015. RESULTS: The review identified that intimate partner
violence exerts a significant impact on the mental health of older women.
Intimate partner violence for women in later life is inherently complex,
especially where the boundaries of violence and vulnerability have been blurred
historically both within the intimate partner violence discourse and through
provision and practice. CONCLUSIONS: This study adds to the developing knowledge
and understanding of intimate partner violence for older women as a part of the
growing body of evidence of the impact of intimate partner violence on the health
and well-being of those who experience abuse more generally. When age and gender
intersect with intimate partner violence, there are specific implications and
health professionals and service providers need to be aware of these. RELEVANCE
TO CLINICAL PRACTICE: urses and healthcare professionals are professionally
accountable for the effective management and support of women who have
experienced abuse. It is therefore crucial that they are able to understand and
identify the possible complexity of presentations of abuse and this includes
older women.
PMID- 27487084
TI - An Optimized Method for Quantification of Pathogenic Leptospira in Environmental
Water Samples.
AB - Leptospirosis is a zoonotic disease usually acquired by contact with water
contaminated with urine of infected animals. However, few molecular methods have
been used to monitor or quantify pathogenic Leptospira in environmental water
samples. Here we optimized a DNA extraction method for the quantification of
leptospires using a previously described Taqman-based qPCR method targeting
lipL32, a gene unique to and highly conserved in pathogenic Leptospira. QIAamp
DNA mini, MO BIO PowerWater DNA and PowerSoil DNA Isolation kits were evaluated
to extract DNA from sewage, pond, river and ultrapure water samples spiked with
leptospires. Performance of each kit varied with sample type. Sample processing
methods were further evaluated and optimized using the PowerSoil DNA kit due to
its performance on turbid water samples and reproducibility. Centrifugation
speeds, water volumes and use of Escherichia coli as a carrier were compared to
improve DNA recovery. All matrices showed a strong linearity in a range of
concentrations from 106 to 10 degrees leptospires/mL and lower limits of
detection ranging from <1 cell /ml for river water to 36 cells/mL for ultrapure
water with E. coli as a carrier. In conclusion, we optimized a method to quantify
pathogenic Leptospira in environmental waters (river, pond and sewage) which
consists of the concentration of 40 mL samples by centrifugation at 15,000*g for
20 minutes at 4 degrees C, followed by DNA extraction with the PowerSoil DNA
Isolation kit. Although the method described herein needs to be validated in
environmental studies, it potentially provides the opportunity for effective,
timely and sensitive assessment of environmental leptospiral burden.
PMID- 27487085
TI - Beneficial effect of arterial embolization with warmed miriplatin for multiple
hepatocellular carcinoma.
AB - AIM: The effect of transcatheter arterial chemoembolization (TACE) is not
necessarily sufficient in patients with multiple hepatocellular carcinoma (HCC).
We evaluated the antitumor activity and adverse events of TACE using warmed
miriplatin suspension for multiple HCC. METHODS: Seventy patients with multiple
HCC received TACE using warmed miriplatin/lipiodol suspension, including patients
who were TACE-naive (group A, n = 5), those undergoing initial TACE after radical
therapies (group B, n = 31), and those with a history of repeated TACE (group C,
n = 34). Median tumor size was 19.5 mm and a median of four nodules. RESULTS:
Complete necrosis (TE 4) and partial necrosis (TE 3) of 50% or more were attained
in 24 and 19 patients at 3 months after TACE, respectively. Response rates (TE 4
+ TE 3) were 60.0% in group A, 83.9% in group B, and 41.2% in group C (P =
0.038). Survival rates of all patients after TACE were 82.6% after 1 year, 65.6%
after 2 years, and 47.7% after 3 years. Three-year survival rates of patients in
groups A, B, and C were 53.3%, 78.8%, and 29.7%, respectively (P = 0.0029).
CONCLUSION: Transcatheter arterial chemoembolization using warmed miriplatin
induced high response rate in multiple HCC, and the rate was significantly high
in those patients with recurrent multiple HCCs after curative therapies.
PMID- 27487086
TI - Thermostability of Well-Ordered HIV Spikes Correlates with the Elicitation of
Autologous Tier 2 Neutralizing Antibodies.
AB - In the context of HIV vaccine design and development, HIV-1 spike mimetics
displaying a range of stabilities were evaluated to determine whether more
stable, well-ordered trimers would more efficiently elicit neutralizing
antibodies. To begin, in vitro analysis of trimers derived from the cysteine
stabilized SOSIP platform or the uncleaved, covalently linked NFL platform were
evaluated. These native-like trimers, derived from HIV subtypes A, B, and C,
displayed a range of thermostabilities, and were "stress-tested" at varying
temperatures as a prelude to in vivo immunogenicity. Analysis was performed both
in the absence and in the presence of two different adjuvants. Since partial
trimer degradation was detected at 37 degrees C before or after formulation with
adjuvant, we sought to remedy such an undesirable outcome. Cross-linking (fixing)
of the well-ordered trimers with glutaraldehyde increased overall
thermostability, maintenance of well-ordered trimer integrity without or with
adjuvant, and increased resistance to solid phase-associated trimer unfolding.
Immunization of unfixed and fixed well-ordered trimers into animals revealed that
the elicited tier 2 autologous neutralizing activity correlated with overall
trimer thermostability, or melting temperature (Tm). Glutaraldehyde fixation also
led to higher tier 2 autologous neutralization titers. These results link
retention of trimer quaternary packing with elicitation of tier 2 autologous
neutralizing activity, providing important insights for HIV-1 vaccine design.
PMID- 27487088
TI - Tuning Cationic Block Copolymer Micelle Size by pH and Ionic Strength.
AB - The formation, morphology, and pH and ionic strength responses of cationic block
copolymer micelles in aqueous solutions have been examined in detail to provide
insight into the future development of cationic micelles for complexation with
polyanions such as DNA. Diblock polymers composed of a hydrophilic/cationic block
of N,N-dimethylaminoethyl methacrylate (DMAEMA) and a hydrophobic/nonionic block
of n-butyl methacrylate (BMA) were synthesized [denoted as DMAEMA-b-BMA (X-Y),
where X = DMAEMA molecular weight and Y = molecular weight of BMA in kDa]. Four
variants were created with block molecular weights of 14-13, 14-23, 27-14, 27-29
kDa and low dispersities less than 1.10. The amphiphilic polymers self-assembled
in aqueous conditions into core-shell micelles that ranged in size from 25-80 nm.
These cationic micelles were extensively characterized in terms of size and net
charge in different buffers over a wide range of ionic strength (0.02-1 M) and pH
(5-10) conditions. The micelle core is kinetically trapped, and the corona
contracts with increasing pH and ionic strength, consistent with previous work on
micelles with glassy polystyrene cores, indicating that the corona properties are
independent of the dynamics of the micelle core. The contraction and extension of
the corona scales with solution ionic strength and charge fraction of the amine
groups. The aggregation numbers of the micelles were obtained by static light
scattering, and the Rg/Rh ratios are close to that of a hard sphere. The zeta
potentials of the micelles were positive up to two pH units above the corona pKa,
suggesting that applications relying on micelle charge for stability should be
viable over a wide range of solution conditions.
PMID- 27487087
TI - Chemistry of Renieramycins. 15. Synthesis of 22-O-Ester Derivatives of
Jorunnamycin A and Their Cytotoxicity against Non-Small-Cell Lung Cancer Cells.
AB - Eighteen 22-O-ester derivatives of jorunnamycin A (2) were prepared via 2, and
their cytotoxicity against human non-small-cell lung cancer (NSCLC) cells was
evaluated. Preliminary study of the structure-cytotoxicity relationship revealed
that the ester part containing a nitrogen-heterocyclic ring elevated the
cytotoxicity of the 22-O-ester derivatives. Among them, 22-O-(4-pyridinecarbonyl)
ester 6a is the most potent compound (IC50 1.1 and 1.6 nM), exhibiting 21-fold
and 5-fold increases in cytotoxicity against the H292 and H460 NSCLC cell lines,
respectively, relative to renieramycin M (1), the major cytotoxic
bistetrahydroisoquinolinequinone alkaloid of the Thai blue sponge Xestospongia
sp.
PMID- 27487089
TI - Noble-metal Ag nanoparticle chains: annealing Ag/Bi superlattice nanowires in
vacuum.
AB - One-dimensional noble-metal Ag nanoparticle chains have been prepared by
electrodepositing Ag/Bi superlattice nanowires in a porous anodic alumina oxide
(AAO) template and following an annealing process in vacuum. It is found that Bi,
as a sacrificial metal, can be removed completely after annealing at 450 degrees
C with a vacuum degree of 10(-5) Torr. The regulation of particle size, shape and
interparticle spacing of Ag NP chains has been realized by adjusting the segment
length of the Ag/Bi superlattice nanowires and the annealing condition. With an
extension of the annealing time, it is observed that Ag particles display the
transform trend from ellipsoid to sphere. Our findings could inspire further
investigation on the design and fabrication of metal nanoparticle chains.
PMID- 27487090
TI - Extent, Awareness and Perception of Dissemination Bias in Qualitative Research:
An Explorative Survey.
AB - BACKGROUND: Qualitative research findings are increasingly used to inform
decision-making. Research has indicated that not all quantitative research on the
effects of interventions is disseminated or published. The extent to which
qualitative researchers also systematically underreport or fail to publish
certain types of research findings, and the impact this may have, has received
little attention. METHODS: A survey was delivered online to gather data regarding
non-dissemination and dissemination bias in qualitative research. We invited
relevant stakeholders through our professional networks, authors of qualitative
research identified through a systematic literature search, and further via
snowball sampling. RESULTS: 1032 people took part in the survey of whom 859
participants identified as researchers, 133 as editors and 682 as peer reviewers.
68.1% of the researchers said that they had conducted at least one qualitative
study that they had not published in a peer-reviewed journal. The main reasons
for non-dissemination were that a publication was still intended (35.7%),
resource constraints (35.4%), and that the authors gave up after the paper was
rejected by one or more journals (32.5%). A majority of the editors and peer
reviewers "(strongly) agreed" that the main reasons for rejecting a manuscript of
a qualitative study were inadequate study quality (59.5%; 68.5%) and inadequate
reporting quality (59.1%; 57.5%). Of 800 respondents, 83.1% "(strongly) agreed"
that non-dissemination and possible resulting dissemination bias might undermine
the willingness of funders to support qualitative research. 72.6% and 71.2%,
respectively, "(strongly) agreed" that non-dissemination might lead to
inappropriate health policy and health care. CONCLUSIONS: The proportion of non
dissemination in qualitative research is substantial. Researchers, editors and
peer reviewers play an important role in this. Non-dissemination and resulting
dissemination bias may impact on health care research, practice and policy. More
detailed investigations on patterns and causes of the non-dissemination of
qualitative research are needed.
PMID- 27487091
TI - Determining mean fractional anisotropy using DDCOSY: preliminary results in
biological tissues.
AB - Complex materials are ubiquitous in science, engineering and nature. One
important parameter for characterising their morphology is the degree of
anisotropy. Magnetic resonance imaging offers non-invasive methods for
quantitative measurements of the materials anisotropy, most commonly via
diffusion tensor imaging and the subsequent extraction of the spatially resolved
fractional anisotropy (FA) value. Here, we propose an alternative way of
determining the FA as a sample average for cases where spatially resolved methods
are not needed or not applicable. It is based on a particular diffusion-diffusion
correlation spectroscopy protocol, allowing for the extraction of the mean (i.e.
sample averaged) FA value. We demonstrate that mean FA values obtained from three
anisotropic biological tissues are consistent with those extracted using
diffusion tensor imaging. Moreover, we show that differences of mean FA values in
healthy and tumour-bearing mouse brains allow to distinguish these tissue types.
We anticipate that the proposed method will be beneficial in the wider context of
medical and material science. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27487092
TI - Risk-Reduction Program for Cardiovascular and Limb Events in Patients With
Peripheral Arterial Disease.
PMID- 27487093
TI - A model assessment of the ability of lake water in Terra Nova Bay, Antarctica, to
induce the photochemical degradation of emerging contaminants.
AB - The shallow lakes located in Terra Nova Bay, Antarctica, are free from ice for
only up to a couple of months (mid December to early/mid February) during the
austral summer. In the rest of the year, the ice cover shields the light and
inhibits the photochemical processes in the water columns. Previous work has
shown that chromophoric dissolved organic matter (CDOM) in these lakes is very
reactive photochemically. A model assessment is here provided of lake-water
photoreactivity in field conditions, based on experimental data of lake water
absorption spectra, chemistry and photochemistry obtained previously, taking into
account the water depth and the irradiation conditions of the Antarctic summer.
The chosen sample contaminants were the solar filter benzophenone-3 and the
antimicrobial agent triclosan, which have very well known photoreactivity and
have been found in a variety of environmental matrices in the Antarctic
continent. The two compounds would have a half-life time of just a few days or
less in the lake water during the Antarctic summertime, largely due to reaction
with CDOM triplet states ((3)CDOM*). In general, pollutants that occur in the ice
and could be released to lake water upon ice melting (around or soon after the
December solstice) would be quickly photodegraded if they undergo fast reaction
with (3)CDOM*. With some compounds, the important (3)CDOM* reactions might favour
the production of harmful secondary pollutants, such as 2,8-dichlorodibenzodioxin
from the basic (anionic) form of triclosan.
PMID- 27487094
TI - Photoelectrochemical removal of 17beta-estradiol using a RuO2-graphene electrode.
AB - A new electrode for the photoelectrochemical removal of 17beta-estradiol from
water using ruthenium oxide nanoparticles supported on reduced graphene oxide is
proposed in this study. The morphology, microstructure and the electrochemical
performance of the material were characterized using HRTEM, XRD and Raman
spectroscopy. The characterization showed the formation of reduced graphene oxide
from a micro-wave assisted hydrothermal method with a particle size of 5.0 nm +
2.4 nm. The electrochemical measurements point to a high performance of the
electrode in the presence of a white light source. The hormone removal efficiency
in water containing 50 MUmol L(-1) of 17beta-estradiol was evaluated using
chronoamperometry at +1.0 V and the process was monitored using liquid
chromatography. The reaction is pseudo first order with the removal of 92.2% of
17beta-estradiol after 60 min of photoelectrocatalytic treatment.
PMID- 27487095
TI - Prospects for arbuscular mycorrhizal fungi (AMF) to assist in phytoremediation of
soil hydrocarbon contaminants.
AB - Arbuscular mycorrhizal fungi (AMF) form mutualistic associations with the roots
of 80-90% of vascular plant species and may constitute up to 50% of the total
soil microbial biomass. AMF have been considered to be a tool to enhance
phytoremediation, as their mycelium create a widespread underground network that
acts as a bridge between plant roots, soil and rhizosphere microorganisms.
Abundant extramatrical hyphae extend the rhizosphere thus creating the
hyphosphere, which significantly increases the area of a plant's access to
nutrients and contaminants. The paper presents and evaluates the role and
significance of AMF in phytoremediation of hydrocarbon contaminated sites. We
focused on (1) an impact of hydrocarbons on arbuscular mycorrhizal symbiosis, (2)
a potential of AMF to enhance phytoremediation, (3) determinants that influence
effectiveness of hydrocarbon removal from contaminated soils. This knowledge may
be useful for selection of proper plant and fungal symbionts and crucial to
optimize environmental conditions for effective AMF-mediated phytoremediation. It
has been concluded that three-component phytoremediation systems based on
synergistic interactions between plant roots, AMF and hydrocarbon-degrading
microorganisms demonstrated high effectiveness in dissipation of organic
pollutants in soil.
PMID- 27487096
TI - Role of Janus-Kinases in Major Depressive Disorder.
AB - BACKGROUND/AIMS: Major depressive disorder is a severe, common and often chronic
disease with a significant mortality due to suicide. The pathogenesis of major
depression is still unknown. It is assumed that a reduction of neurogenesis in
the hippocampus plays an important role in the development of major depressive
disorder. However, the mechanisms that control proliferation of neuronal stem
cells in the hippocampus require definition. Here, we investigated the role of
Janus-Kinase 3 (Jak-3) for stress-induced inhibition of neurogenesis and the
induction of major depression symptoms in mice. METHODS: Stress was induced by
the application of glucocorticosterone. Brain sections were stained with phospho
specific antibodies and analysed by confocal microscopy to measure
phosphorylation of Jak-3 specifically in the hippocampus. Jak-3 inhibitors and
the antidepressant amitriptyline were applied to counteract stress. The effects
of the inhibitors were determined by a set of behavioural tests and analysis of
Jak-3 phosphorylation in brain sections. Acid sphingomyelinase-deficient mice
were employed to test whether Jak3 is downstream of ceramide. RESULTS: The data
show that stress reduces neurogenesis, which is restored by simultaneous
application of Jak-3 inhibitors. Inhibition of neurogenesis correlated with an
anxious-depressive behaviour that was also normalized upon application of a Jak-3
inhibitor. Confocal microscopy data revealed that stress triggers a
phosphorylation and thereby activation of Jak-3 in the hippocampus.
Amitriptyline, a commonly used antidepressant that blocks the acid
sphingomyelinase, or acid sphingomyelinase-deficiency reduced stress-induced
phosphorylation of Jak-3. CONCLUSION: Our data show that Jak-3 is activated by
stress at least partially via the acid sphingomyelinase and is involved in the
mediation of stress-induced major depression.
PMID- 27487098
TI - Letter from the editor: the campaign button.
PMID- 27487097
TI - Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated
Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single
Centre Experience of Four Decades of Growth Hormone Replacement.
AB - BACKGROUND: Growth hormone (GH) has been used to treat children with GH
deficiency (GHD) since 1966. AIMS: Using a combined retrospective and cross
sectional approach, we explored the long-term outcomes of patients with GHD,
analysed factors influencing therapeutic response, determined persistence into
adulthood, investigated pituitary morphology, and screened for mutations in
causative genes. METHODS: The files of 96 GH-deficient children were reviewed. In
a subset of 50 patients, re-assessment in adulthood was performed, including GHRH
arginine testing, pituitary magnetic resonance imaging (MRI), and mutational
screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR)
in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in
multiple pituitary hormone deficiency (MPHD) patients. RESULTS: GH was started at
a height SDS of -3.2 +/- 1.4 in IGHD patients and of -4.1 +/- 2.1 in MPHD
patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and
1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in
77%. Initial height SDS, bone age retardation and duration of GH replacement were
correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of
subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation
was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary
hypoplasia, combined with posterior pituitary ectopy and pituitary stalk
invisibility on MRI, was an exclusive finding in MPHD patients. CONCLUSIONS: GH
replacement successfully corrects the growth deficit in children with GHD. While
the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations
constitute a major cause for MPHD. Persistence of GHD into adulthood is related
to abnormal pituitary morphology.
PMID- 27487099
TI - The role of talimogene laherparepvec (T-VEC) in the age of checkpoint inhibitors.
PMID- 27487100
TI - Are we ready for precision medicine in acute myeloid leukemia?
PMID- 27487101
TI - Sorafenib in combination with transarterial chemoembolization for the treatment
of hepatocellular carcinoma.
PMID- 27487102
TI - Highlights in kidney cancer from the 2016 American Society of Clinical Oncology
Annual Meeting.
PMID- 27487103
TI - Recent advances in the management of myelofibrosis.
PMID- 27487104
TI - Improving clinical trial design through quantitative pharmacology.
PMID- 27487105
TI - Moving beyond monotherapy in the immunotherapeutic arena: prospects for
combination therapies in lung cancer.
PMID- 27487106
TI - The status of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in
ovarian cancer, part 1: olaparib.
AB - Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have shown
promising clinical activity in epithelial ovarian cancer. Following the
observation in vitro that PARP inhibition is synthetically lethal in tumors with
BRCA mutations, PARP inhibition has become the first genotype-directed therapy
for BRCA1- and BRCA2-associated ovarian cancer. However, it is becoming clear
that PARP inhibition also may have clinical utility in cancers associated with
defects or aberrations in DNA repair that are unrelated to BRCA mutations.
Deficient DNA repair mechanisms are present in approximately 30% to 50% of high
grade serous ovarian cancers, the most common histologic subtype. Olaparib is the
best-studied PARP inhibitor to date, and a number of phase 3 trials with this
agent are underway. This article reviews the development of olaparib for ovarian
cancer and discusses the current evidence for its use, ongoing studies, future
research directions, and the challenges ahead.
PMID- 27487107
TI - Trifluridine/tipiracil and regorafenib: new weapons in the war against metastatic
colorectal cancer.
AB - Colorectal cancer (CRC) is the second leading cause of cancer-related death in
the United States. Approximately 20% of patients have metastatic disease at
diagnosis, and a vast number of these patients die within 5 years. The advent of
modern chemotherapeutics has improved median overall survival for these patients;
nonetheless, we must keep striving for better outcomes. Trifluridine/tipiracil
(TAS-102) and regorafenib are agents newly approved by the US Food and Drug
Administration that show promise in the treatment of metastatic colorectal
cancer. These drugs have the benefit of being formulated for oral administration
and have different side effect profiles. These differences are important in the
selection of the best therapy for each patient, especially if the patient is
prone to a side effect that is unique to just one of the treatments. In this
review, we discuss the mechanism of action, side effect profile, and clinical
efficacy of trifluridine/tipiracil, and compare them with those of regorafenib.
Future trials will evaluate the use of these drugs in earlier lines of therapy,
alone and in combination with other agents. We now have 2 more agents in the
arsenal against metastatic colorectal cancer and the future is looking brighter
for patients, although we still have a long way to go.
PMID- 27487108
TI - Impact of XRCC1, GSTP1, and GSTM1 Polymorphisms on the Survival of Ovarian
Carcinoma Patients Treated with Chemotherapy.
AB - BACKGROUND: Single nucleotide polymorphic variants of DNA repair genes may
improve drug efficacy through altering expression levels of the encoded proteins.
This study evaluated the influence of genetic polymorphism GSTP1 Ile105Val, GSTM1
(null/non-null) and 2 XRCC1 polymorphisms (Arg194Trp and Arg399Gln) on the
survival of ovarian carcinoma patients treated with chemotherapy. METHODS: 106
patients received treatment with a carboplatin-based or alternative chemotherapy.
Polymorphisms were genotyped by pyrosequencing. RESULTS: The genotypes XRCC1
194Arg/Trp and XRCC1 194Trp/Trp conferred no significant risk of death when
compared to 194Arg/Arg (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.33
3.09, and HR 0.89, 95% CI 0.31-2.57, respectively). Similarly, those carrying the
XRCC1 399Arg/Gln genotype had no increased risk of death compared to the XRCC1
399Arg/Arg (HR 0.85, 95% CI 0.39-1.86); no homozygous carriers of the glutamine
allele (XRCC1 399 Gln/Gln) were detected. The GSTP1 105Ile/Val had no increased
risk of death compared to the GSTP1 105Ile/Ile (HR = 1.20, 95% CI = 0.55-2.63)
and no homozygous carriers of the valine allele (GSTP1 105Val/Val) were detected
in the study. Compared to the non-null genotype of GSTM1, the mortality rate was
nonsignificantly reduced in patients with the null genotype (HR 1.07, 95% CI 0.48
2.42). However, overall survival of the patients treated with the carboplatin
based regimen was significantly longer than for those treated with alternative
chemotherapy (plog-rank = 0.006). CONCLUSIONS: The present findings suggest that
there are no correlations between genotypes and survival.
PMID- 27487109
TI - Post-Operative Infection Is an Independent Risk Factor for Worse Long-Term
Survival after Colorectal Cancer Surgery.
AB - BACKGROUND: Colorectal cancer surgery is associated with a high incidence of post
operative infections, the outcome of which may be improved if diagnosed and
treated early enough. We compared white blood cell (WBC) count, C-reactive
protein (CRP), and procalcitonin (PCT) as predictors of post-operative infections
and analyzed their impact on long-term survival. METHODS: This retrospective
study included 186 patients undergoing colorectal surgery. Post-operative values
of WBC, CRP, and PCT were analyzed by the receiver operating characteristic (ROC)
analysis. We followed infections 30 d after the surgery. A five-year survival was
analyzed by Kaplan-Meier method and prognostic factors by Cox regression model.
RESULTS: Fifty-five patients (29.5%) developed post-operative infection, the most
frequent of which was surgical site infection (SSI). C-reactive protein on post
operative day three and PCT on post-operative day two demonstrated the highest
diagnostic accuracy for infection (area under the curve [AUC] 0.739 and 0.735). C
reactive protein on post-operative day three was an independent predictor of
infection. Five-year survival was higher in the non-infected group (70.8%),
compared with the infected group (52.1%). The worst survival (40.9%) was
identified in patients with organ/space SSI. Post-operative infection and tumor
stage III-IV were independent predictors of a worse five-year survival.
CONCLUSIONS: C-reactive protein on post-operative day three and PCT on post
operative day two may be early predictors of infection after colorectal cancer
surgery. Post-operative infections in particular organ/space SSI have a negative
impact on long-term survival.
PMID- 27487110
TI - Veterinary Student Confidence after Practicing with a New Surgical Training Model
for Feline Ovariohysterectomy.
AB - Lack of confidence and self-efficacy are the main causes of negative emotions
experienced by veterinary students when performing surgery. A surgical training
model (STM) was developed to test the hypothesis that practical training on an
STM before performing live surgery would enhance the students' confidence. In
addition, low-cost and easily accessible materials were used for the
construction. In the STM, neodymium magnets that were detached if too much
traction was applied were used to ensure careful tissue handling during ligation
of the ovarian pedicles and cervix. A pilot study was performed to evaluate
veterinary undergraduate students' confidence when using the STM before
performing their first live feline ovariohysterectomy (OHE) as lead surgeon. The
results showed that the students rated their confidence level higher after
performing feline OHE if they had practiced with the STM before surgery.
Voluntary written comments revealed that live surgery as a learning situation
could have a very negative emotional impact on some students.
PMID- 27487111
TI - Assessing Professionalism: A Theoretical Framework for Defining Clinical Rotation
Assessment Criteria.
AB - Although widely accepted as an important graduate competence, professionalism is
a challenging outcome to define and assess. Clinical rotations provide an
excellent opportunity to develop student professionalism through the use of
experiential learning and effective feedback, but without appropriate theoretical
frameworks, clinical teachers may find it difficult to identify appropriate
learning outcomes. The adage "I know it when I see it" is unhelpful in providing
feedback and guidance for student improvement, and criteria that are more
specifically defined would help students direct their own development. This study
sought first to identify how clinical faculty in one institution currently assess
professionalism, using retrospective analysis of material obtained in
undergraduate teaching and faculty development sessions. Subsequently, a faculty
workshop was held in which a round-table type discussion sought to develop these
ideas and identify how professionalism assessment could be improved. The output
of this session was a theoretical framework for teaching and assessing
professionalism, providing example assessment criteria and ideas for clinical
teaching. This includes categories such as client and colleague interaction,
respect and trust, recognition of limitations, and understanding of different
professional identities. Each category includes detailed descriptions of the
knowledge, skills, and behaviors expected of students in these areas. The
criteria were determined by engaging faculty in the development of the framework,
and therefore they should represent a focused development of criteria already
used to assess professionalism, and not a novel and unfamiliar set of assessment
guidelines. The faculty-led nature of this framework is expected to facilitate
implementation in clinical teaching.
PMID- 27487112
TI - A Guide for Making Valid Interpretations of Student Evaluation of Teaching (SET)
Results.
AB - Student evaluations of teaching (SETs) are conducted in virtually every
veterinary medical school in the world. Results of these evaluations are
typically used to evaluate faculty performance and often serve as the primary
basis for promotion and tenure decisions. However, given the high-stakes nature
of these evaluations, it is critical that stakeholders (faculty, curriculum
committees, department chairs, deans, etc.) be able to identify the extent to
which the scores are likely to be valid or not. Thus, the purpose of this article
was to develop a guide for faculty and administrators to assess the
interpretative validity of SET scores given an array of sample size, response
rate, and score standard deviation possibilities.
PMID- 27487113
TI - Use of Examination Wrappers to Direct Student Self-Assessment of Examination
Preparation: A Pilot Study.
AB - Metacognition is the act of thinking about one's own thought processes. There are
long-term gains in learning among students who are trained to understand how the
brain works and how they can control their own learning. Wrappers are short
questionnaires provided at or near the time of completion of a lecture,
assignment, or assessment to coach the student in thinking through the steps of
metacognition (planning, monitoring, and adapting). As students completed the
second and third of four examinations in a first-year veterinary anatomy course,
they were invited to fill out an examination wrapper that asked them questions
about examination preparation, where they felt they had had the most trouble with
the examination, and what they might do differently before the next examination.
Neither percentage change in scores from the second to the third and from the
third to the fourth lecture or laboratory examination nor final grade for the
course varied between the group of students who completed an examination wrapper
and the group that did not. Students did not appear to change their behavior from
one examination to the next. This was most likely because students lacked formal
training in metacognition and therefore did not understand the value of
completing the examination wrapper or the potential benefits of using their
reflections. Future work will describe outcomes when learning objectives specific
to metacognition are included in coursework in the veterinary curriculum.
PMID- 27487114
TI - Prohibiting Students from Asking Questions during Exams: A Guideline for
Promoting Fairness and Preserving Score Validity.
AB - Many medical and professional programs implement policies that prohibit students
from asking questions during examinations. The reasoning behind these policies
remains unclear to some, as there is a lack of literature addressing this topic.
The purpose of this article is to present the rationale behind such policies and
to discuss why these policies may help promote fairness and preserve score
validity.
PMID- 27487115
TI - Micro-mechanical modelling of cellulose aerogels from molten salt hydrates.
AB - In this paper, a generalised micro-mechanical model capable of capturing the
mechanical behaviour of polysaccharidic aerogels, in particular cellulose
aerogels, is proposed. To this end, first the mechanical structure and properties
of these highly nanoporous cellulose aerogels prepared from aqueous salt hydrate
melts (calcium thiocyanate, Ca(SCN)2.6H2O and zinc chloride, ZnCl2.4H2O) are
studied. The cellulose content within these aerogels is found to have a direct
relation to the microstructural quantities such as the fibril length and
diameter. This, along with porosity, appears to influence the resulting
mechanical properties. Furthermore, experimental characterisation of cellulose
aerogels was done using scanning electron microscopy (SEM), pore-size data
analysis, and compression tests. Cellulose aerogels are of a characteristic
cellular microstructures and accordingly a network formed by square shaped cells
is considered in the micro-mechanical model proposed in this paper. This model is
based on the non-linear bending and collapse of such cells of varying pore sizes.
The extended Euler-Bernoulli beam theory for large deflections is used to
describe the bending in the cell walls. The proposed model is physically
motivated and demonstrates a good agreement with our experimental data of both
ZnCl2 and Ca(SCN)2 based cellulose aerogels with different cellulose contents.
PMID- 27487116
TI - Effectiveness and Economic Evaluation of Chiropractic Care for the Treatment of
Low Back Pain: A Systematic Review of Pragmatic Studies.
AB - BACKGROUND CONTEXT: Low back pain (LBP) is one of the leading causes of
disability worldwide and among the most common reasons for seeking primary sector
care. Chiropractors, physical therapists and general practitioners are among
those providers that treat LBP patients, but there is only limited evidence
regarding the effectiveness and economic evaluation of care offered by these
provider groups. PURPOSE: To estimate the clinical effectiveness and to
systematically review the literature of full economic evaluation of chiropractic
care compared to other commonly used care approaches among adult patients with
non-specific LBP. STUDY DESIGN: Systematic reviews of interventions and economic
evaluations. METHODS: A comprehensive search strategy was conducted to identify
1) pragmatic randomized controlled trials (RCTs) and/or 2) full economic
evaluations of chiropractic care for low back pain compared to standard care
delivered by other healthcare providers. Studies published between 1990 and 4th
June 2015 were considered. Primary outcomes included pain, functional status and
global improvement. Study selection, critical quality appraisal and data
extraction were conducted by two independent reviewers. Data from RCTs with low
risk of bias were included in a meta-analysis to determine effect estimates. Cost
estimates of full economic evaluations were converted to 2015 USD and results
summarized using Slavin's qualitative best-evidence synthesis. RESULTS: Six RCTs
and three full economic evaluations were scientifically admissible. Five RCTs
with low risk of bias compared chiropractic care to exercise therapy (n = 1),
physical therapy (n = 3) and medical care (n = 1). Overall, we found similar
effects for chiropractic care and the other types of care and no reports of
serious adverse events. Three low to high quality full economic evaluations
studies (one cost-effectiveness, one cost-minimization and one cost-benefit)
compared chiropractic to medical care. Given the divergent conclusions (favours
chiropractic, favours medical care, equivalent options), mixed-evidence was found
for economic evaluations of chiropractic care compared to medical care.
CONCLUSION: Moderate evidence suggests that chiropractic care for LBP appears to
be equally effective as physical therapy. Limited evidence suggests the same
conclusion when chiropractic care is compared to exercise therapy and medical
care although no firm conclusion can be reached at this time. No serious adverse
events were reported for any type of care. Our review was also unable to clarify
whether chiropractic or medical care is more cost-effective. Given the limited
available evidence, the decision to seek or to refer patients for chiropractic
care should be based on patient preference and values. Future studies are likely
to have an important impact on our estimates as these were based on only a few
admissible studies.
PMID- 27487117
TI - The Influence of Climate Change Efficacy Messages and Efficacy Beliefs on
Intended Political Participation.
AB - Using an online survey experiment with a national sample, this study examined how
changing the type and valence of efficacy information in news stories discussing
global climate change may impact intended political participation through the
mediators of perceived internal, external, and response efficacy. Overall, the
results revealed that after a single exposure to a news story, stories including
positive internal efficacy content increased perceived internal efficacy, while
stories including negative external efficacy content lowered perceived external
efficacy. There were limited impacts of other types of efficacy content on
perceived efficacy. Perceived internal, external, and response efficacy all
offered unique, positive associations with intentions to engage in climate change
related political participation. The results suggest that news stories including
positive internal efficacy information in particular have the potential to
increase public engagement around climate change. The implications for science
communication are discussed.
PMID- 27487119
TI - Correction to Direct Tracking of Amyloid and Tau Dynamics in Neuroblastoma Cells
Using Nanoplasmonic Fiber Tip Probes.
PMID- 27487118
TI - Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through
IGF1/IGF1R Signaling under Hypoxia.
AB - Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity,
with an extremely poor prognosis because of its highly invasive nature. PDAC
proliferates with abundant stromal cells, suggesting that its invasive activity
might be controlled by intercellular interactions between cancer cells and
fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated
fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and
IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA.
Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9) was
examined by immunohistochemical staining of 120 pancreatic specimens. The effects
of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined
by wound-healing assay or invasion assay under normoxia (20% O2) and hypoxia (1%
O2). IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT
cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in
RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R
expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC
cells did not. A conditioned medium from CAFs, which expressed alphaSMA,
stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT
cells. The motility of all PDAC cells was greater under hypoxia than under
normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R
inhibitors. These findings might suggest that pancreas CAFs stimulate the
invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling,
especially under hypoxia. Therefore the targeting of IGF1R signaling might
represent a promising therapeutic approach in IGF1R-dependent PDAC.
PMID- 27487120
TI - Siderophores in Cloud Waters and Potential Impact on Atmospheric Chemistry:
Photoreactivity of Iron Complexes under Sun-Simulated Conditions.
AB - In the present work, the photoreactivity of a mixture of iron(III)-pyoverdin
(Fe(III)-Pyo) complexes was investigated under simulated cloud conditions.
Pyoverdins are expected to complex ferric ions naturally present in cloudwater,
thus modifying their availability and photoreactivity. The spectroscopic
properties and photoreactivity of Fe(III)-Pyo were investigated, with particular
attention to their fate under solar irradiation, also studied through
simulations. The photolysis of the Fe(III)-Pyo complex leads to the generation of
Fe(II), with rates of formation (RFe(II)f) of 6.98 and 3.96 * 10-9 M s-1 at pH
4.0 and 6.0, respectively. Interestingly, acetate formation was observed during
the iron-complex photolysis, suggesting that fragmentation can occur after the
ligand-to-metal charge transfer (LMCT) via a complex reaction mechanism.
Moreover, photogenerated Fe(II) represent an important source of hydroxyl radical
via the Fenton reaction in cloudwater. This reactivity might be relevant for the
estimation of the rates of formation and steady-state concentrations of the
hydroxyl radical by cloud chemistry models and for organic matter speciation in
the cloud aqueous phase. In fact, the conventional models, which describe the
iron photoreactivity in terms of iron-aqua and oxalate complexes, are not in
accordance with our results.
PMID- 27487121
TI - Effect of the Chronic Use of Lithium Carbonate on Induced Tooth Movement in
Wistar Rats.
AB - Patients who seek dental treatment may have bipolar disorder, and lithium
carbonate (LC) is the drug of choice used in the treatment of this disorder.
Taking into consideration the controversial results found in the literature, and
the possible influence of LC on induced tooth movement, the objective was to
evaluate tooth movement induced in rats after administration of lithium
carbonate. One hundred and ninety-two rats were divided into 3 groups. In the L
group, the animals received daily 60mg/kg of LC, they were not subjected to
orthodontic movement, and they were euthanized after 33, 37, 44 or 51 days. In
the LM group, the LC was administered for 30 days and during the subsequent 3, 7,
14 and 21 days, corresponding to the period of induced tooth movement, and they
received a spring that produced a 30cN force. In the SM group, saline solution
was applied. Measurements were made of tooth displacement, the numbers of
osteoclasts and serum lithium phosphate (PO4), alkaline phosphatase (ALP) and
creatinine levels. The tooth displacement was lower in the LM group compared to
the SM group at 44 days. A tendency toward reduction in the number of osteoclasts
was observed in the LM group compared to the SM group at 44 days. The average
lithium were higher in the L and LM groups compared to the SM group. The opposite
was observed for the PO4 group. A higher value for the ALP was found in the L
group. The average creatinine level was lower in the LM group. LC inhibited tooth
movement for 14 days, possibly due to the reduction in the number of osteoclasts.
PMID- 27487122
TI - Interleukin-11 promotes epithelial-mesenchymal transition in anaplastic thyroid
carcinoma cells through PI3K/Akt/GSK3beta signaling pathway activation.
AB - Metastasis is the major cause of treatment failure in anaplastic thyroid
carcinoma (ATC) patients. In the preliminary study, we demonstrated that
interleukin (IL)-11 expression is positively correlated with distant metastasis
in ATC. However, the mechanisms underlying remain largely unknown. Here, we found
that cobalt chloride (a hypoxia mimetic) promoted IL-11 expression via HIF-1alpha
activation. Furthermore, the resultant increase in IL-11 expression significantly
induced epithelial-mesenchymal transition (EMT) in ATC cells, accompanied by
Akt/GSK3beta pathway activation and increased invasive and migratory abilities.
Conversely, HIF-1alpha or IL-11 knockdown, or treating cells with a neutralizing
antibody against IL-11, a PI3K inhibitor, or Akt inhibitor V, significantly
suppressed the induction of EMT and counteracted the enhancements in invasive and
migratory abilities. These results indicate that hypoxia increases IL-11
secretion in ATC cells via HIF-1alpha induction and that IL-11 then induces EMT
in these cells via the PI3K/Akt/GSK3beta pathway, ultimately improving their
invasive and migratory potential. This study elucidates the prometastatic role
played by IL-11 in ATC metastasis and indicates it as a potential target for the
treatment of cancer metastasis. However, many questions remain to be explored.
PMID- 27487123
TI - KDM4B-mediated epigenetic silencing of miRNA-615-5p augments RAB24 to facilitate
malignancy of hepatoma cells.
AB - Emerging evidence indicates that dysregulation of microRNAs (miRNAs) contributes
to hepatocellular carcinoma (HCC) tumorigenesis and development. Here, we found
that miR-615-5p was obviously downregulated in HCC. Furthermore, the deficiency
of demethylase KDM4B stimulated the CpG methylation of miR-615-5p promoter and
then decreased the miR-615-5p expression. The Ras-related protein RAB24 was found
to be downregulated by miR-615-5p. The low level of miR-615-5p increased the
expression of RAB24 and facilitated HCC growth and metastasis in vitro and in
vivo. Moreover, miR-615-5p suppresses HCC cell growth by influencing cell cycle
progression and apoptosis. Downregulation of miR-615-5p and upregulation of RAB24
promotes the epithelial-mesenchymal transition (EMT), adhesion and vasculogenic
mimicry (VM) of HCC cells, all of which contribute to cell motility and
metastasis. Thus, miR-615-5p, who is downregulated by KDM4B-mediated
hypermethylation in its promoter, functions as a tumor suppressor by inhibiting
RAB24 expression in HCC. In conclusion, our findings characterize miR-615-5p as
an important epigenetically silenced miRNA involved in the Rab-Ras pathway in
hepatocellular carcinoma and expand our understanding of the molecular mechanism
underlying hepatocarcinogenesis and metastasis.
PMID- 27487124
TI - Downregulated pseudogene CTNNAP1 promote tumor growth in human cancer by
downregulating its cognate gene CTNNA1 expression.
AB - Accumulating evidence indicates that deregulation of cancer-associated pseudogene
is involved in the pathogenesis of cancer. In the study, we demonstrated that
pseudogene CTNNAP1, for the CTNNA1 gene, was dysregulated in colorectal cancer
and the degree of dysregulation was remarkably associated with tumor node
metastasis (TNM) stage (P<0.05). The mechanistic experiments revealed that
pseudogene CTNNAP1 played a pivotal role in the regulation of its cognate gene
CTNNA1 by competition for microRNA-141. Moreover, gain-of-function approaches
showed that overexpression of CTNNAP1 or CTNNA1 significantly inhibited cell
proliferation and tumor growth in vitro and in vivo by inducing G0/G1 cell cycle
arrest. Our findings add a new regulatory circuit via competing endogenous RNA
(ceRNA) cross-talk between pseudogene CTNNAP1 and its cognate gene CTNNA1, and
provide new insights into potential diagnostic biomarker for monitoring human
colorectal cancer.
PMID- 27487125
TI - The application of mRNA-based gene transfer in mesenchymal stem cell-mediated
cytotoxicity of glioma cells.
AB - Since the tumor-oriented homing capacity of mesenchymal stem cells (MSCs) was
discovered, MSCs have attracted great interest in the research field of cancer
therapy mainly focused on their use as carries for anticancer agents. Differing
from DNA-based vectors, the use of mRNA-based antituor gene delivery benefits
from readily transfection and mutagenesis-free. However, it is essential to
verify if mRNA transfection interferes with MSCs' tropism and their antitumor
properties. TRAIL- and PTEN-mRNAs were synthesized and studied in an in vitro
model of MSC-mediated indirect co-culture with DBTRG human glioma cells. The
expression of TRAIL and PTEN in transfected MSCs was verified by immunoblotting
analysis, and the migration ability of MSCs after anticancer gene transfection
was demonstrated using transwell co-cultures. The viability of DBTRG cells was
determined with bioluminescence, live/dead staining and real time cell analyzer.
An in vivo model of DBTRG cell-derived xenografted tumors was used to verify the
antitumor effects of TRAIL- and PTEN-engineered MSCs. With regard to the effect
of mRNA transfection on MSCs' migration toward glioma cells, an enhanced
migration rate was observed with MSCs transfected with all tested mRNAs compared
to non-transfected MSCs (p<0.05). TRAIL- and PTEN-mRNA-induced cytotoxicity of
DBTRG glioma cells was proportionally correlated with the ratio of conditioned
medium from transfected MSCs. A synergistic action of TRAIL and PTEN was
demonstrated in the current co-culture model. The immunoblotting analysis
revealed the apoptotic nature of the cells death in the present study. The growth
of the xenografted tumors was significantly inhibited by the application of
MSCPTEN or MSCTRAIL/PTEN on day 14 and MSCTRAIL on day 28 (p<0.05). The results
suggested that anticancer gene-bearing mRNAs synthesized in vitro are capable of
being applied for MSC-mediated anticancer modality. This study provides an
experimental base for further clinical anticancer studies using synthesized
mRNAs.
PMID- 27487126
TI - LncRNA RSU1P2 contributes to tumorigenesis by acting as a ceRNA against let-7a in
cervical cancer cells.
AB - Long non-coding RNAs (lncRNAs) can regulate gene expression at different levels
and are widely participate in various physiological and pathological processes.
Emerging evidences suggests that a number of differentially expressed lncRNAs are
involved in tumorigenesis. However, the function and expression regulation of a
vast majority of these unique RNAs is little known. Here, we found that the
lncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) is upregulateded in
cervical cancer tissues and has a tumour-promoting role. We revealed that RSU1P2
acts as a competitive endogenous RNA (ceRNA) through regulating the expression of
IGF1R, N-myc and EphA4. The mechanism of this regulation is via competition for
the shared microRNA let-7a. This competition promotes the malignant phenotype of
cervical carcinoma cells. The transcription factor N-myc forms a positive
feedback loop with RSU1P2 by in turn activating its expression, thereby enhancing
its oncogenic capacity. Hence, cancer-selective targeting of RSU1P2 could have
strong benefits.
PMID- 27487127
TI - miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance
associated protein-1.
AB - Multidrug resistance-associated protein 1 (MRP1) is an important efflux
transporter and overexpression of MRP1 usually leads to chemoresistance in breast
cancer. Here, we found MRP1 overexpressed in human breast cancer tissues and
breast cancer cell lines (compared with normal breast tissues and cell line,
respectively). And MRP1 level increased in doxorubicin resistant MCF-7 cells
compared with parental MCF-7 cells. Increasing evidences suggest microRNAs
(miRNAs) influence chemotherapy response. We found miR-145 level decreased in
human breast cancer tissues, breast cancer cell lines and doxorubicin resistant
MCF-7 cells, and inversely correlated with MRP1 expression level. In the process
of constructing MCF-7 doxorubicin resistant cell line, escalating doxorubicin
markedly decreased miR-145 level, following by increased MRP1 level. Further
study showed, miR-145 suppressed MRP1 expression by directly targeting MRP1 3'
untranslated regions. Overexpression of miR-145 sensitized breast cancer cells to
doxorubicin in vitro and enhanced to doxorubicin chemotherapy in vivo through
inducing intracellular doxorubicin accumulation via inhibiting MRP1. Taken
together, our study revealed miR-145 sensitizes breast cancer to doxorubicin by
targeting MRP1 and indicated the potential application in developing MRP1
inhibitor.
PMID- 27487128
TI - Ethacrynic acid improves the antitumor effects of irreversible epidermal growth
factor receptor tyrosine kinase inhibitors in breast cancer.
AB - Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR)
tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a
narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR
TKIs is to combine them with drugs used for other clinical indications.
Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and
may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione
and inhibiting WNT signaling. While the alpha,beta-unsaturated-keto structure of
EA is similar to that of irreversible TKIs, the mechanism of action of EA when
combined with irreversible EGFR TKIs in breast cancer remains unknown. We
therefore investigated the combination of irreversible EGFR TKIs and EA. We found
that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in
vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell
cycle arrest and represses WNT/beta-catenin signaling as well as MAPK-ERK1/2
signaling. We conclude that EA synergistically enhances the antitumor effects of
irreversible EGFR TKIs in breast cancer.
PMID- 27487129
TI - Bortezomib-induced heat shock response protects multiple myeloma cells and is
activated by heat shock factor 1 serine 326 phosphorylation.
AB - Proteasome inhibitors such as bortezomib are highly active in multiple myeloma by
affecting signaling cascades and leading to a toxic buildup of misfolded
proteins. Bortezomib-treated cells activate the cytoprotective heat shock
response (HSR), including upregulation of heat shock proteins (HSPs). Here we
inhibited the bortezomib-induced HSR by silencing its master regulator, Heat
Shock Factor 1 (HSF1). HSF1 silencing led to bortezomib sensitization. In
contrast, silencing of individual and combination HSPs, except HSP40beta, did not
result in significant bortezomib sensitization. However, HSP40beta did not
entirely account for increased bortezomib sensitivity upon HSF1 silencing. To
determine the mechanism of HSF1 activation, we assessed phosphorylation and
observed bortezomib-inducible phosphorylation in cell lines and patient samples.
We determined that this bortezomib-inducible event is phosphorylation at serine
326. Prior clinical use of HSP inhibitors in combination with bortezomib has been
disappointing in multiple myeloma therapy. Our results provide a rationale for
targeting HSF1 activation in combination with bortezomib to enhance multiple
myeloma treatment efficacy.
PMID- 27487130
TI - Targeting hyperactivated DNA-PKcs by KU0060648 inhibits glioma progression and
enhances temozolomide therapy via suppression of AKT signaling.
AB - The overall survival remains undesirable in clinical glioma treatment. Inhibition
of DNA-PKcs activity by its inhibitors suppresses tumor growth and enhances
chemosensitivity of several tumors to chemotherapy. However, whether DNA-PKcs
could be a potential target in glioma therapy remains unknown. In this study, we
reported that the hyperactivated DNA-PKcs was profoundly correlated with glioma
malignancy and observe a significant association between DNA-PKcs activation and
survival of the glioma patients. Our data also found that inhibition of DNA-PKcs
by its inhibitor KU0060648 sensitized glioma cells to TMZ in vitro. Specifically,
we demonstrated that KU0060648 interrupted the formation of DNA-PKcs/AKT complex,
leading to suppression of AKT signaling and resultantly enhanced TMZ efficacy.
Combination of KU0060648 and TMZ substantially inhibited downstream effectors of
AKT. The in vivo results were similar to those obtained in vitro. In conclusion,
this study indicated that inhibition of DNA-PKcs activity could suppress glioma
malignancies and increase TMZ efficacy, which was mainly through regulation of
the of AKT signaling. Therefore, DNA-PKcs/AKT axis may be a promising target for
improving current glioma therapy.
PMID- 27487131
TI - Integrin beta3 and CD44 levels determine the effects of the OPN-a splicing
variant on lung cancer cell growth.
AB - Osteopontin (OPN), a phosphorylated glycoprotein, is frequently overexpressed in
cancer. Among the three OPN isoforms, OPN-a is the most highly expressed in lung
cancer cell lines and lung tumors. Overexpression of OPN-a greatly reduced CL1-5
lung adenocarcinoma cell growth, but had no effect on growth in A549 lung
adenocarcinoma cells. Examination of the expression of integrins and CD44, which
are possible OPN-a receptors, revealed that differences in integrin beta3 levels
might explain this discrepancy between CL1-5 and A549 cells. When integrin beta3
was ectopically expressed in A549 cells, OPN-a inhibited their growth, whereas
OPN-a increased cell growth following integrin beta3 knockdown in CL1-5 cells.
This OPN-a-induced increase in growth appeared to result from activation of the
CD44/NFkappaB pathway. Our results demonstrated that OPN-a inhibits growth of
cells with high integrin beta3 levels and increases growth via activation of the
CD44/NFkappaB pathway in cells with low integrin beta3 levels. Thus, OPN-a,
integrin beta3, and CD44 interact to affect lung cancer cell growth, and this
study may aid in the development of cancer treatment strategies involving these
molecules.
PMID- 27487132
TI - YMO1 suppresses invasion and metastasis by inhibiting RhoC signaling and predicts
favorable prognosis in hepatocellular carcinoma.
AB - Previous studies have shown that 4.1 proteins, which are deregulated in many
cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1)
is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in
tumor invasion. This study aimed to investigate the effects of YMO1 on
hepatocellular carcinoma (HCC) and attempted to elucidate the underlying
molecular mechanisms. YMO1 expression in HCC tissues and its correlation with
clinicopathological features and postoperative prognosis was analyzed. The
results showed that YMO1 was down-regulated in the highly metastatic HCC cell
line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis
of HCC patients. Restoration of YMO1 expression caused a significant decrease in
cell migration and invasiveness in vitro. In vivo study showed that YMO1 reduced
liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited
RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1
expression levels in human HCC patients revealed a significant correlation of
YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts
favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and
metastasis by inhibiting RhoC activity.
PMID- 27487134
TI - Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium
wilfordii via multiple mechanisms.
AB - A leading cause of cancer chemotherapy failure is chemoresistance, which often
involves multiple mechanisms. Chinese medicines (CM) usually contain multiple
components which could potentially target many mechanisms simultaneously and may
offer an advantage over single compounds that target one mechanism at a time. The
purpose of this study was to investigate the chemosensitizing effect (CE) of a
specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to
docetaxel (Dtx) and identify the potential mechanisms. The CE of TW (in
combination with Dtx) was evaluated in two Dtx resistant prostate cancer cell
lines (PC3-TxR and DU145-TxR) and the efficacy of the combination for resistant
PC3-TxR tumor was investigated using a xenograft mouse model. For mechanistic
study, the inhibitory effect of TW on P-glycoprotein activity was assessed. In
addition, novel gene targets of TW were identified using DNA microarray and
quantitative PCR. Results showed that TW induced a CE of 8 and >38 folds in PC3
TxR and DU145-TxR cells, respectively with Dtx IC50 reversed back to that of the
sensitive parent cells. An optimum dose of TW+Dtx significantly retarded tumor
growth in mice compared to TW or Dtx alone. TW inhibited P-glycoprotein activity
and induced a significant gene expression changes in genes related to
angiogenesis, cell cycle regulation and differentiation. Our in vitro and in vivo
studies demonstrate that TW in combination with Dtx was able to overcome the
chemoresistance and suppress resistant prostate tumor growth via multi
mechanisms.
PMID- 27487135
TI - Tumor exosome-mediated promotion of adhesion to mesothelial cells in gastric
cancer cells.
AB - BACKGROUND: Peritoneal metastasis consists of a highly complex series of steps,
and the details of the underlying molecular mechanism remain largely unclear. In
this study, the effects of tumor-derived exosomes (TEX) on the progression of
gastric cancers were investigated in peritoneal metastasis. RESULTS: TEX were
internalized in both mesothelial and gastric cancer cells in a cellular origin
non-specific manner. Internalization of TEX into mesothelial cells promoted
significant adhesion between mesothelial and gastric cancer cells, and TEX
internalization into gastric cancer cells significantly promoted migratory
ability, while internalization of mesothelial cell-derived exosomes did not.
Expression of adhesion-related molecules, such as fibronectin 1 (FN1) and laminin
gamma 1 (LAMC1), were increased in mesothelial cells after internalization of TEX
from gastric cancer cell line and malignant pleural effusion. METHODS: TEX were
extracted from cell-conditioned medium by ultracentrifugation. The effects of TEX
on the malignant potential of gastric cancer were investigated in adhesion,
invasion, and proliferation assays. PCR array as well as western blotting were
performed to determine the underlying molecular mechanisms. The molecular changes
in mesothelial cell after internalization of TEX derived from malignant pleural
effusion were also confirmed. CONCLUSIONS: TEX may play a critical role in the
development of peritoneal metastasis of gastric cancer, which may be partially
due to inducing increased expression of adhesion molecules in mesothelial cells.
PMID- 27487136
TI - Caveolin-1 promotes Ewing sarcoma metastasis regulating MMP-9 expression through
MAPK/ERK pathway.
AB - Ewing sarcoma (ES) is a bone and soft tissue sarcoma affecting mostly children
and young adults. Caveolin-1 (CAV1) is a well-known target of EWS/FLI1, the main
driver of ES, with an oncogenic role in ES. We have previously described how CAV1
is able to induce metastasis in ES via matrix metalloproteinase-9 (MMP-9). In the
present study we showed how CAV1 silencing in ES reduced MEK1/2 and ERK1/2
phosphorylation. Accordingly, chemical inhibition of MEK1/2 resulted in reduction
in MMP-9 expression and activity that correlated with reduced migration and
invasion. IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) silencing
reduced MEK1/2 and ERK1/2 phosphorylation and MMP-9 expression. Furthermore,
IQGAP1 silenced cells showed a marked decrease in their migratory and invasive
capacity. We demonstrated that CAV1 and IQGAP1 localize in close proximity at the
cellular edge, thus IQGAP1 could be the connecting node between CAV1 and MEK/ERK
in ES metastatic phenotype. Analysis of the phosphorylation profile of CAV1
silenced cells showed a decrease of p-ribosomal protein S6 (RPS6). RPS6 can be
phosphorylated by p90 ribosomal S6 kinases (RSK) proteins. CAV1-silenced cells
showed reduced levels of p-RSK1 and treatment with U0126 provoked the same
effect. Despite not affecting ERK1/2 and RPS6 phosphorylation status neither MMP
9 expression nor activity, RSK1 silencing resulted in a reduced migratory and
invasive capacity in vitro and reduced incidence of metastases in vivo in a novel
orthotopic model. The present work provides new insights into CAV1-driven
metastatic process in ES unveiling novel key nodes.
PMID- 27487137
TI - Decreased expression of FOXF2 as new predictor of poor prognosis in stage I non
small cell lung cancer.
AB - BACKGROUND: Forkhead box F2 (FOXF2) is relatively limited to the adult lung, but
its contribution to non-small cell lung cancer (NSCLC) prognosis is unclear.
RESULTS: FOXF2 mRNA levels in NSCLC were lower than that in paired normal lung
tissues (P = 0.012). The FOXF2low patients had shorter survival time than the
FOXF2high patients (P = 0.024) especially in stage I (P = 0.002), chemotherapy (P
= 0.018) and < 60 age groups (P = 0.002). Lower FOXF2 mRNA levels could
independently predict poorer survival for patients with NSCLC (HR = 2.384, 95% CI
= 1.241-4.577; P = 0.009), especially in stage I (HR =4.367, 95% CI =1.599
11.925; P = 0.004). The two independent datasets confirmed our findings. METHODS:
We examined FOXF2 mRNA levels in 84 primary NSCLC and 8 normal lung tissues using
qRT-PCR. Rank-sum tests and chi-square tests were used to assess the differences
among groups with various clinicopathological factors. Kaplan-Meier tests were
used to compare survival status in patients with different FOXF2 mRNA levels. Cox
proportional hazards regression model was used to evaluate the predictive value
of FOXF2 mRNA level in NSCLC patients. Independent validation was performed using
an independent dataset (98 samples) and an online survival analysis software
Kaplan-Meier plotter (1928 samples). CONCLUSIONS: Our results demonstrated that
decreased FOXF2 expression is an independent predictive factor for poor prognosis
of patients with NSCLC, especially in stage I NSCLC.
PMID- 27487138
TI - The microRNA signature of patients with sunitinib failure: regulation of UHRF1
pathways by microRNA-101 in renal cell carcinoma.
AB - Molecular targeted therapy is a standard treatment for patients with advanced
renal cell carcinoma (RCC). Sunitinib is one of the most common molecular
targeted drugs for metastatic RCC. Molecular mechanisms of sunitinib resistance
in RCC cells is still ambiguous. The microRNA (miRNA) expression signature of
patients with sunitinib failure in RCC was constructed using a polymerase chain
reaction (PCR)-based array. Several miRNAs that were aberrantly expressed in RCC
tissues from patients treated with sunitinib were identified in this analysis.
MicroRNA-101 (miR- 101) was markedly suppressed in sunitinib treated RCC tissues.
Restoration of miR-101 significantly inhibited cell migration and invasion in
Caki-1 and 786-O cells. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1)
was directly suppressed by miR-101 in RCC cells, and overexpression of UHRF1 was
confirmed in sunitinib-treated RCC tissues. The pathways of nucleotide excision
repair and mismatch repair were significantly suppressed by knockdown of UHRF1.
Our findings showed that antitumor miR-101- mediated UHRF1 pathways may be
suppressed by sunitinib treatment.
PMID- 27487139
TI - Construction and analysis of dysregulated lncRNA-associated ceRNA network
identified novel lncRNA biomarkers for early diagnosis of human pancreatic
cancer.
AB - It is increasing evidence that ceRNA activity of long non-coding RNAs (lncRNAs)
played critical roles in both normal physiology and tumorigenesis. However,
functional roles and regulatory mechanisms of lncRNAs as ceRNAs in pancreatic
ductal adenocarcinoma (PDAC), and their potential implications for early
diagnosis remain unclear. In this study, we performed a genome-wide analysis to
investigate potential lncRNA-mediated ceRNA interplay based on "ceRNA
hypothesis". A dysregulated lncRNA-associated ceRNA network (DLCN) was
constructed by utilizing sample-matched miRNA, lncRNA and mRNA expression
profiles in PDAC and normal samples in combination with miRNA regulatory network.
The results of network analysis uncovered seven novel lncRNAs as functional
ceRNAs whose aberrant expression will result in the extensive variation in
tumorigenic or tumor-suppressive gene expression through DLCN at the post
transcriptional level contributing to PDAC. Therefore, we developed a 7-lncRNA
signature (termed LncRisk-7) based on the expression data of seven lncRNAs and
SVM algorithm as a novel diagnostic tool to improve early diagnosis of PDAC. The
LncRisk-7 achieved high performance in distinguishing PDAC patients from
nonmalignant pancreas samples in the discovery cohort and was further confirmed
in another two independent validation cohorts. Functional analysis demonstrated
that seven lncRNA biomarkers act as ceRNAs involving the regulation of cell
death, cell adhesion and cell cycle. This study will help to improve our
understanding of the lncRNA-mediated ceRNA regulatory mechanisms in the
pathogenesis of PDAC and provide novel lncRNAs as candidate diagnostic biomarkers
or potential therapeutic targets.
PMID- 27487140
TI - High expression of intratumoral stromal proteins is associated with chemotherapy
resistance in breast cancer.
AB - We studied the changes of intratumoral stromal proteins including THBS1, TNC, FN,
SPARC and alpha-SMA, following neoadjuvant chemotherapy. The underlying
mechanisms by which THBS1 and TNC regulated resistance to docetaxel were further
studied using functional studies. 100 patients with newly diagnosed breast cancer
were treated with alternating sequential doxorubicin and docetaxel.
Immunohistochemistry (IHC) staining for stromal proteins was performed on pre-
and post-treatment core biopsies respectively. THBS1 and TNC were further
validated with IHC in an independent cohort of 31 patients. A high baseline
combined expression score of the 5 stromal proteins predicted independently for
poor progression-free (HRadjusted 2.22, 95% CI 1.06-4.64) and overall survival
(HRadjusted 5.94, 95% CI 2.25-15.71). After 1-2 cycles of chemotherapy, increased
expression of THBS1, TNC, FN, SPARC and alpha-SMA was seen in patients with
subsequent pathological lymph node involvement at surgery. Increased expression
of THBS1 and TNC compared to baseline was also seen in intrinsically resistant
tumors, but not in sensitive ones. Both THBS1 and TNC-associated chemoresistance
were confirmed in an independent validation cohort. Exogenous THBS1 and TNC
protected MCF-7 cells against proliferation inhibition induced by docetaxel
through activating integrin beta1/mTOR pathway. Thus, up-regulation of THBS1,
TNC, FN, SPARC and alpha-SMA following neoadjuvant chemotherapy was associated
with chemotherapy resistance in breast cancer patients. Functional studies showed
THBS1 and TNC to mediate chemoresistance through the integrin beta1/mTOR pathway,
suggesting that therapies targeting integrin beta1/mTOR pathway may be a
promising strategy to overcome chemotherapy resistance.
PMID- 27487141
TI - Integrin alphaVbeta3 silencing sensitizes malignant glioma cells to temozolomide
by suppression of homologous recombination repair.
AB - Integrins have been suggested as possible targets in anticancer therapy. Here we
show that knockdown of integrins alphaVbeta3, alphaVbeta5, alpha3beta1 and
alpha4beta1 and pharmacological inhibition using a cyclo-RGD integrin
alphaVbeta3/alphaVbeta5 antagonist sensitized multiple high-grade glioma cell
lines to temozolomide (TMZ)-induced cytotoxicity. The greatest effect was
observed in LN229 cells upon integrin beta3 silencing, which led to inhibition of
the FAK/Src/Akt/NFkappaB signaling pathway and increased formation of gammaH2AX
foci. The integrin beta3 knockdown led to the proteasomal degradation of Rad51,
reduction of Rad51 foci and reduced repair of TMZ-induced DNA double-strand
breaks by impairing homologous recombination efficiency. The down-regulation of
beta3 in Rad51 knockdown (LN229-Rad51kd) cells neither further sensitized them to
TMZ nor increased the number of gammaH2AX foci, confirming causality between
beta3 silencing and Rad51 reduction. RIP1 was found cleaved and IkappaBalpha
significantly less degraded in beta3-silenced/TMZ-exposed cells, indicating
inactivation of NFkappaB signaling. The anti-apoptotic proteins Bcl-xL, survivin
and XIAP were proteasomally degraded and caspase-3/-2 cleaved. Increased H2AX
phosphorylation, caspase-3 cleavage, reduced Rad51 and RIP1 expression, as well
as sustained IkappaBalpha expression were also observed in mouse glioma
xenografts treated with the cyclo-RGD inhibitor and TMZ, confirming the molecular
mechanism in vivo. Our data indicates that beta3 silencing in glioma cells
represents a promising strategy to sensitize high-grade gliomas to TMZ therapy.
PMID- 27487142
TI - Blood baseline neutrophil count predicts bevacizumab efficacy in glioblastoma.
AB - Bevacizumab is used to treat glioblastoma; however, no current biomarker predicts
its efficacy. We used an exploratory cohort of patients treated with the
radiochemotherapy then bevacizumab or chemotherapy at recurrence (N = 265).
Bevacizumab use increased median overall survival (OS) 18.7 vs 11.3 months, p =
0.0014). In multivariate analysis, age, initial surgery, neutrophil count,
Karnofsky status >70% and bevacizumab administration were independent prognostic
factors of survival. We found an interaction between bevacizumab use and baseline
neutrophil count. The cut-off value for the neutrophil count was set at 6000/mm3.
Only patients with a high neutrophil count benefited from the bevacizumab
treatment (17.3 vs 8.8 months p < 0.0001). We validated this result using data
from the TEMAVIR trial, which tested the efficacy of neoadjuvant bevacizumab plus
irinotecan versus radiochemotherapy in the first-line treatment of glioblastoma.
Transcriptomic data from TCGA underlined that CSF3 expression, the gene encoding
G-CSF, the growth factor for neutrophils, correlated with VEGF-A-dependent
angiogenesis. In another independent cohort (BELOB trial), which compared
lomustine versus lomustine plus bevacizumab at recurrence, bevacizumab only
benefited patients with high CSF3 expression in the tumor. These data suggest
that only patients with a high peripheral neutrophil count before bevacizumab
treatment benefited from this therapy.
PMID- 27487143
TI - Targeting Zfp148 activates p53 and reduces tumor initiation in the gut.
AB - The transcription factor Zinc finger protein 148 (Zfp148, ZBP-89, BFCOL, BERF1,
htbeta) interacts physically with the tumor suppressor p53, but the significance
of this interaction is not known. We recently showed that knockout of Zfp148 in
mice leads to ectopic activation of p53 in some tissues and cultured fibroblasts,
suggesting that Zfp148 represses p53 activity. Here we hypothesize that targeting
Zfp148 would unleash p53 activity and protect against cancer development, and
test this idea in the APCMin/+ mouse model of intestinal adenomas. Loss of one
copy of Zfp148 markedly reduced tumor numbers and tumor-associated intestinal
bleedings, and improved survival. Furthermore, after activation of beta-catenin
the initiating event in colorectal cancer-Zfp148 deficiency activated p53 and
induced apoptosis in intestinal explants of APCMin/+ mice. The anti-tumor effect
of targeting Zfp148 depended on p53, as Zfp148 deficiency did not affect tumor
numbers in APCMin/+ mice lacking one or both copies of Trp53. The results suggest
that Zfp148 controls the fate of newly transformed intestinal tumor cells by
repressing p53 and that targeting Zfp148 might be useful in the treatment of
colorectal cancer.
PMID- 27487145
TI - Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global
genome repair.
AB - UVB exposure leads to DNA damage, which when unrepaired induces C>T transitions.
These mutations are found throughout the melanoma genome, particularly in non
transcribed regions. The global genome repair (GGR) branch of nucleotide excision
repair (NER) is responsible for repairing UV-induced DNA damage across non
transcribed and silent regions of the genome. This study aimed to examine the
relationship between UVB and GGR in melanoma. DNA repair capacity and relative
expression of NER in melanocytes and melanoma cell lines before and after
treatment with UVB was quantified. Transcript expression from 196 melanomas was
compared to clinical parameters including solar elastosis and whole transcriptome
data collected. Melanoma cell lines showed significantly reduced DNA repair when
compared to melanocytes, most significantly in the S phase of the cell cycle.
Expression of GGR components XPC, DDB1 and DDB2 was significantly lower in
melanoma after UVB. In the melanoma tumours, XPC expression correlated with age
of diagnosis and low XPC conferred significantly poorer survival. The same trend
was seen in the TCGA melanoma dataset. Reduced GGR in melanoma may contribute to
the UV mutation spectrum of the melanoma genome and adds further to the growing
evidence of the link between UV, NER and melanoma.
PMID- 27487144
TI - Molecular mechanisms underlying resistance to androgen deprivation therapy in
prostate cancer.
AB - Prostate cancer (PCa) is the most widely diagnosed male cancer in the Western
World and while low- and intermediate-risk PCa patients have a variety of
treatment options, metastatic patients are limited to androgen deprivation
therapy (ADT). This treatment paradigm has been in place for 75 years due to the
unique role of androgens in promoting growth of prostatic epithelial cells via
the transcription factor androgen receptor (AR) and downstream signaling
pathways. Within 2 to 3 years of ADT, disease recurs-at which time, patients are
considered to have castration-recurrent PCa (CR-PCa). A universal mechanism by
which PCa becomes resistant to ADT has yet to be discovered. In this review
article, we discuss underlying molecular mechanisms by which PCa evades ADT.
Several major resistance pathways center on androgen signaling, including
intratumoral and adrenal androgen production, AR-overexpression and
amplification, expression of AR mutants, and constitutively-active AR splice
variants. Other ADT resistance mechanisms, including activation of glucocorticoid
receptor and impairment of DNA repair pathways are also discussed. New therapies
have been approved for treatment of CR-PCa, but increase median survival by only
2-8 months. We discuss possible mechanisms of resistance to these new ADT agents.
Finally, the practicality of the application of "precision oncology" to this
continuing challenge of therapy resistance in metastatic or CR-PCa is examined.
Empirical validation and clinical-based evidence are definitely needed to prove
the superiority of "precision" treatment in providing a more targeted approach
and curative therapies over the existing practices that are based on biological
"cause-and-effect" relationship.
PMID- 27487146
TI - Nomogram and recursive partitioning analysis to predict overall survival in
patients with stage IIB-III thoracic esophageal squamous cell carcinoma after
esophagectomy.
AB - We have developed statistical models for predicting survival in patients with
stage IIB-III thoracic esophageal squamous cell carcinoma (ESCC) and assessing
the efficacy of adjuvant treatment. From a retrospective review of 3,636
patients, we created a database of 1,004 patients with stage IIB-III thoracic
ESCC who underwent esophagectomy with or without postoperative radiation. Using a
multivariate Cox regression model, we assessed the prognostic impact of clinical
and histological factors on overall survival (OS). Logistic analysis was
performed to identify factors to include in a recursive partitioning analysis
(RPA) to predict 5-year OS. The nomogram was evaluated internally based on the
concordance index (C-index) and a calibration plot. The median survival time in
the training dataset was 30.9 months, and the 5-year survival rate was 33.9%. T
stage, differentiated grade, adjuvant treatment, tumor location, lymph node
metastatic ratio (LNMR), and the presence of vascular carcinomatous thrombi were
statistically significant predictors of 5-year OS. The C-index of the nomogram
was 0.70 (95% CI 0.67-0.73). RPA resulted in a three-class stratification: class
1, LNMR <= 0.15 with adjuvant treatment; class 2, LNMR <= 0.15 without adjuvant
treatment and LNMR > 0.15 with adjuvant treatment; and class 3, LNMR > 0.15
without adjuvant treatment. The three classes were statistically significant for
OS (P < 0.001). Thus, the nomogram and RPA models predicted the prognosis of
stage IIB-III ESCC patients and could be used in decision-making and clinical
trials.
PMID- 27487147
TI - Significant impact of amount of PCR input templates on various PCR-based DNA
methylation analysis and countermeasure.
AB - Methylation changes of CpG islands can be determined using PCR-based assays.
However, the exact impact of the amount of input templates (TAIT) on DNA
methylation analysis has not been previously recognized. Using COL2A1 gene as an
input reference, TAIT difference between human tissues with methylation-positive
and -negative detection was calculated for two representative genes GFRA1 and
P16. Results revealed that TAIT in GFRA1 methylation-positive frozen samples (n =
332) was significantly higher than the methylation-negative ones (n = 44) (P <
0.001). Similar difference was found in P16 methylation analysis. The TAIT
related effect was also observed in methylation-specific PCR (MSP) and denatured
high performance liquid chromatography (DHPLC) analysis. Further study showed
that the minimum TAIT for a successful MethyLight PCR reaction should be >= 9.4
ng (CtCOL2A1 <= 29.3), when the cutoff value of the methylated-GFRA1 proportion
for methylation-positive detection was set at 1.6%. After TAIT of the methylation
non-informative frozen samples (n = 94; CtCOL2A1 > 29.3) was increased above the
minimum TAIT, the methylation-positive rate increased from 72.3% to 95.7% for
GFRA1 and 26.6% to 54.3% for P16, respectively (Ps < 0.001). Similar results were
observed in the FFPE samples. In conclusion, TAIT critically affects results of
various PCR-based DNA methylation analyses. Characterization of the minimum TAIT
for target CpG islands is essential to avoid false-negative results.
PMID- 27487149
TI - Intra-tumoral delivery of functional ID4 protein via PCL/maltodextrin nano
particle inhibits prostate cancer growth.
AB - ID4, a helix loop helix transcriptional regulator has emerged as a tumor
suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate
cancer whereas ectopic expression in prostate cancer cell lines blocks cancer
phenotype. To directly investigate the anti-tumor property, full length human
recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL
MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably
silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased
apoptosis, decreased proliferation and colony formation. Intratumoral delivery of
PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the
tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The
study supports the feasibility of using nano-carrier encapsulated ID4 protein as
a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways
for example epigenetic re-programming, integration of multiple AR co-regulators
or signaling pathways resulting in tumor suppressor activity of ID4.
PMID- 27487151
TI - ABCC2-24C > T polymorphism is associated with the response to platinum/5-Fu-based
neoadjuvant chemotherapy and better clinical outcomes in advanced gastric cancer
patients.
AB - Several studies have evaluated the efficacy of neoadjuvant treatment using
oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However,
preoperative biomarkers predictive of clinical outcome remain lacking. We
examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and
XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort
of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from
peripheral blood cells, and the genotypes were analyzed using a SNaPShotTM assay,
polymerase chain reaction amplification, and sequencing. The ABCC2-24C > T
(rs717620) genotype was associated with pathologic response to neoadjuvant
chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant
chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27
11.32). Patients with the CC genotype also had poorer outcomes than those with
other genotypes. Thus, ABCC2-24C > T polymorphism may help to predict the
response to preoperative chemotherapy in GC patients.
PMID- 27487152
TI - Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative
breast cancers (TNBCs).
AB - Triple Negative Breast Cancer (TNBC) is defined by the lack of ERalpha, PR
expression and HER2 overexpression and is the breast cancer subtype with the
poorest clinical outcomes. Our aim was to identify genes driving TNBC
proliferation and/or survival which could represent novel therapeutic targets.We
performed microarray profiling of primary TNBCs and generated differential
genelists based on clinical outcomes following the chemotherapy regimen FEC (5
Fluorouracil/Epirubicin/Cyclophosphamide -'good' outcome no relapse > 3 years;
'poor' outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor
(TBXA2R) was observed in 'good' outcome TNBCs. TBXA2R expression was higher
specifically in TNBC cell lines and TBXA2R knockdowns consistently showed
dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up
regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated
transcriptional repression.We demonstrated that TBXA2R enhanced TNBC cell
migration, invasion and activated Rho signalling, phenotypes which could be
reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected
TNBC cells from DNA damage by negatively regulating reactive oxygen species
levels. In summary, TBXA2R is a novel breast cancer-associated gene required for
the survival and migratory behaviour of a subset of TNBCs and could provide
opportunities to develop novel, more effective treatments.
PMID- 27487153
TI - Novel functions of Fanconi anemia proteins in selective autophagy and
inflammation.
PMID- 27487155
TI - Incipient periodontitis and salivary molecules among Korean adults: association
and screening ability.
AB - AIM: This study aims to evaluate the association of salivary matrix
metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) with periodontitis and its
screening ability on periodontitis. MATERIAL AND METHODS: We selected 693
participants from the Yanypyeong Cohort: 577 participants with periodontitis and
116 participants without periodontitis. Periodontitis was assessed by dentists
using a panoramic radiograph. Salivary MMP-9 and IL-8 were assayed using
multiplexed bead immunoassay (Luminex). MMP-9 and IL-8 were categorized into low,
medium and high. Age, sex, income, smoking, drinking, exercise, obesity and
metabolic syndrome were confounders. Logistic regression analysis was applied to
evaluate the association between MMP-9, IL-8 and periodontitis. Receiver
operating characteristic curve was applied for sensitivity, specificity and c
statistics. RESULTS: High MMP-9 and medium IL-8 were associated with
periodontitis: adjusted odds ratio were 2.2 [95% confidence interval (CI): 1.3
3.7] for MMP-9 and 1.9 (95% CI: 1.1-3.4) for IL-8. The final screening model
using salivary MMP-9 for periodontitis had a sensitivity of 0.46, specificity of
0.77 and c-statistic of 0.63 (p < 0.001). CONCLUSIONS: Our data show that
salivary MMP-9 and IL-8 could be potential markers for periodontitis. The
screening model for periodontitis could be useful in clinics and home. A future
prospective study is indicated for predicting the occurrence of periodontitis.
PMID- 27487154
TI - Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal
carcinoma cell interaction promote tumor cell invasiveness.
AB - The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC)
is a malignancy characterized by an intimate relationship between neoplastic
cells and a non-neoplastic lymphoid component. Tumor-associated macrophages
(TAMs) foster tumor progression through production of soluble mediators that
support proliferation, angiogenesis, survival and invasion of malignant cells.
However, the role of macrophages in the progression of NPC remains poorly
understood. This study aims to investigate the functional and phenotypic changes
that occur to macrophages in macrophage-NPC cell co-culture systems, and how
these changes influence tumor cells. We found that monocytes, including THP-1
cells and primary human monocytes, co-cultured with C666-1 NPC cells upregulate
expression of pro-inflammatory cytokines at the early stages, followed by the
induction of metastasis-related genes and interferon-stimulated genes at the
later stage of coculture, indicating that TAMs are "educated" by NPC cells for
cancer progression. Importantly, the induction of these factors from the TAMs was
also found to enhance the migratory capabilities of the NPC cells. We have also
identified one of these macrophage-derived factor, phospholipase A2 Group 7
(PLA2G7), to be important in regulating tumor cell migration and a novel tumor
promoting factor in NPC. Further studies to characterize the role of PLA2G7 in
tumor metastasis may help determine its potential as a therapeutic target in NPC.
PMID- 27487156
TI - Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with
Clinical Features and Th1 Response.
AB - OBJECTIVES: Since lipid compounds are known to modulate the function of CD4+ T
cells and macrophages, we hypothesize that altered levels of serum non-esterified
fatty acids (NEFA) may underlie rheumatoid arthritis (RA) pathogenesis. METHODS:
Serum levels of NEFA (palmitic, stearic, palmitoleic, oleic, linoleic, gamma
linoleic, arachidonic -AA-, linolenic, eicosapentaenoic -EPA- and docosahexaenoic
-DHA-) were quantified by LC-MS/MS after methyl-tert-butylether (MTBE)-extraction
in 124 RA patients and 56 healthy controls (HC). CD4+ phenotype was studied by
flow cytometry. TNFalpha, IL-8, VEGF, GM-CSF, IFNgamma, IL-17, CCL2, CXCL10,
leptin and resistin serum levels were quantified by immunoassays. The effect of
FA on IFNgamma production by PBMC was evaluated in vitro. RESULTS: Lower levels
of palmitic (p<0.0001), palmitoleic (p = 0.002), oleic (p = 0.010), arachidonic
(p = 0.027), EPA (p<0.0001) and DHA (p<0.0001) were found in RA patients, some
NEFA being altered at onset. Cluster analysis identified a NEFA profile
(hallmarked by increased stearic and decreased EPA and DHA) overrepresented in RA
patients compared to HC (p = 0.002), being associated with clinical features (RF,
shared epitope and erosions), increased IFNgamma expression in CD4+ T-cells (p =
0.002) and a Th1-enriched serum milieu (IFNgamma, CCL2 and CXCL10, all p<0.005).
In vitro assays demonstrated that imbalanced FA could underlie IFNgamma
production by CD4+ T-cells. Finally, changes on NEFA levels were associated with
clinical response upon TNFalpha-blockade. CONCLUSION: An altered NEFA profile can
be found in RA patients associated with clinical characteristics of aggressive
disease and enhanced Th1 response. These results support the relevance of
lipidomic studies in RA and provide a rationale for new therapeutic targets.
PMID- 27487157
TI - B Cell Receptor Activation Predominantly Regulates AKT-mTORC1/2 Substrates
Functionally Related to RNA Processing.
AB - Protein kinase B (AKT) phosphorylates numerous substrates on the consensus motif
RXRXXpS/T, a docking site for 14-3-3 interactions. To identify novel AKT-induced
phosphorylation events following B cell receptor (BCR) activation, we performed
proteomics, biochemical and bioinformatics analyses. Phosphorylated consensus
motif-specific antibody enrichment, followed by tandem mass spectrometry,
identified 446 proteins, containing 186 novel phosphorylation events. Moreover,
we found 85 proteins with up regulated phosphorylation, while in 277 it was down
regulated following stimulation. Up regulation was mainly in proteins involved in
ribosomal and translational regulation, DNA binding and transcription regulation.
Conversely, down regulation was preferentially in RNA binding, mRNA splicing and
mRNP export proteins. Immunoblotting of two identified RNA regulatory proteins,
RBM25 and MEF-2D, confirmed the proteomics data. Consistent with these findings,
the AKT-inhibitor (MK-2206) dramatically reduced, while the mTORC-inhibitor PP242
totally blocked phosphorylation on the RXRXXpS/T motif. This demonstrates that
this motif, previously suggested as an AKT target sequence, also is a substrate
for mTORC1/2. Proteins with PDZ, PH and/or SH3 domains contained the consensus
motif, whereas in those with an HMG-box, H15 domains and/or NF-X1-zinc-fingers,
the motif was absent. Proteins carrying the consensus motif were found in all
eukaryotic clades indicating that they regulate a phylogenetically conserved set
of proteins.
PMID- 27487159
TI - Variation in the use of point-of-care ultrasound in general practice in various
European countries. Results of a survey among experts.
AB - BACKGROUND: Before implementing point-of-care ultrasound in general practice in
Denmark, we sought inspiration from other countries/regions. OBJECTIVES: To
collect information about the use and organizational aspects of point-of-care
ultrasound in general practice in different European countries/regions. METHODS:
Fifteen key persons with knowledge about the use of ultrasound in general
practice in Austria, Catalonia, Denmark, Finland, Germany, Greenland, Iceland,
the Netherlands, Norway, Scotland, Sweden, and Switzerland were included.
Participants received a link to a web-based questionnaire. The primary outcome
measures were educational aspects regarding the use of point-of-care ultrasound;
clinical application and use; financial aspects; and main barriers to using
ultrasound in general practice. RESULTS: In eight out of 12 countries/regions
there were national societies for the use of ultrasound in general practice. The
respondents from three countries/regions reported that the use of ultrasound was
integrated into undergraduate medical education. In nine of the
countries/regions, there was formalized training for general practitioners, but
only three reported this to be part of the specialization to become a general
practitioner. In seven out of 12 countries/regions, general practitioners
received payment for ultrasound scans. However, the payment and the requirements
for reimbursement differed between countries. Lack of time, lack of training, and
financial aspects were important common barriers across countries/regions.
CONCLUSION: There were significant differences regarding the use and
organizational aspects of point-of-care ultrasound in general practice in Europe.
Lack of time and training as well as financial aspects were important barriers to
the use of point-of-care ultrasound in general practice.[Box: see text].
PMID- 27487158
TI - New Initiation of Long-Acting Opioids in Long-Stay Nursing Home Residents.
AB - OBJECTIVES: To estimate the prevalence of new initiation of long-acting opioids
since introduction of national efforts to increase prescriber and public
awareness on safe use of transdermal fentanyl patches. DESIGN: Cross-sectional.
SETTING: U.S. nursing homes (NHs). PARTICIPANTS: Medicare-enrolled long-stay NH
residents (N = 22,253). MEASUREMENTS: Minimum Data Set 3.0 was linked with
Medicare enrollment, hospital claims, and prescription drug transaction data
(January-December 2011) and used to determine the prevalence of new initiation of
a long-acting opioid prescribed to residents in NHs. RESULTS: Of NH residents
prescribed a long-acting opioid within 30 days of NH admission (n = 12,278), 9.4%
(95% confidence interval = 8.9-9.9%) lacked a prescription drug claim for a short
acting opioid in the previous 60 days. The most common initial prescriptions of
long-acting opioids were fentanyl patch (51.9% of opioid-naive NH residents),
morphine sulfate (28.1%), and oxycodone (17.2%). CONCLUSION: New initiation of
long-acting opioids-especially fentanyl patches, which have been the subject of
safety communications-persists in NHs.
PMID- 27487160
TI - Ethnic Differences in Mental Illness Severity: A Population-Based Study of
Chinese and South Asian Patients in Ontario, Canada.
AB - OBJECTIVE: Little is known about the sociocultural determinants of mental illness
at hospital presentation. Our objective was to examine ethnic differences in
illness severity at hospital admission among Chinese, South Asian, and the
general population living in Ontario, Canada. METHODS: We conducted a large,
population-based, cross-sectional study of psychiatric inpatients aged from 19 to
105 years who were discharged between 2006 and 2014. A total of 133,588 patients
were classified as Chinese (n = 2,582), South Asian (n = 2,452), or the reference
group (n = 128,554) using a validated surnames algorithm (specificity: 99.7%).
Diagnoses were based on DSM-IV criteria. We examined the association between
ethnicity and 4 measures of disease severity: involuntary admissions, aggressive
behaviors, and the number and frequency of positive symptoms (ie, hallucinations,
command hallucinations, delusions, and abnormal thought process) (Positive
Symptoms Scale, Resident Assessment Instrument-Mental Health [RAI-MH]). RESULTS:
After adjusting for sociodemographic characteristics, immigration status, and
discharge diagnosis, Chinese patients had greater odds of involuntary admissions
(odds ratio [OR] = 1.79; 95% CI, 1.64-1.95) and exhibiting severe aggressive
behaviors (OR = 1.36; 95% CI, 1.23-1.51) and >= 3 positive symptoms (OR = 1.39;
95% CI, 1.24-1.56) compared to the general population. South Asian ethnicity was
also an independent predictor of most illness severity measures. The association
between Chinese ethnicity and illness severity was consistent across sex,
diagnostic and immigrant categories, and first-episode hospitalization.
CONCLUSIONS: Chinese and South Asian ethnicities are independent predictors of
illness severity at hospital presentation. Understanding the role of patient,
family, and health system factors in determining the threshold for
hospitalization is an important future step in informing culturally specific care
for these large and growing populations worldwide.
PMID- 27487161
TI - Comparison of two apheresis systems during hematopoietic progenitor stem cell
collections at a tertiary medical center.
AB - BACKGROUND: The Spectra Optia is a newer apheresis system developed based on the
COBE Spectra platform. COBE Spectra requires more manual control, while Spectra
Optia offers greater automation. The purpose of this study was to compare the two
systems during hematopoietic progenitor stem cell (HPSC) collections. STUDY
DESIGN AND METHODS: A retrospective review of 41 collections performed in 26
subjects at a tertiary medical center between June 1, 2013, and December 31,
2013, was conducted, 11 with the Spectra Optia and 30 with the COBE Spectra. Six
patients underwent two consecutive daily collections, first on the Spectra Optia
followed by the COBE Spectra. RESULTS: Procedure run time with the Spectra Optia
was considerably longer than with the COBE Spectra (283 +/- 11 min vs. 217 +/- 2
min, respectively; p < 0.01). Mean CD34+ cell yields with the Spectra Optia were
comparable with those of the COBE Spectra. Products collected with the Spectra
Optia had less red blood cell contamination. However, platelet (PLT) attrition
was greater with the Spectra Optia. Similar results were obtained in patients who
were collected on consecutive days in both systems. CONCLUSION: Collections with
the Spectra Optia take longer and lead to greater PLT losses during HPSC
collections.
PMID- 27487162
TI - Disentangling the Causal Association of Plasma Lipid Traits and Type 2 Diabetes
Using Human Genetics.
PMID- 27487164
TI - Peripartum Depression, Traditional Culture, and Israeli Society.
AB - Although it is known that culture affects psychopathology, the nature of the
relationship between culture and peripartum depression (PPD) is not fully
understood. Here we report on 2 cases of Israeli women who are affiliated with
traditional cultural groups that emphasize reproduction but developed PPD after
childbirth. The first woman is an ultra-Orthodox Israeli Jew and the second is an
Israeli Arab. The 2 cases illustrate the effect of cultural beliefs and rituals
on the conceptualization, treatment, and trajectory of PPD. The cases suggest a
complex relationship between traditional cultures and PPD, including the
possibility that cultural factors may have both adaptive and maladaptive
consequences. Future qualitative and quantitative studies are needed to further
clarify this relationship.
PMID- 27487163
TI - Increased Lung Expression of Anti-Angiogenic Factors in Down Syndrome: Potential
Role in Abnormal Lung Vascular Growth and the Risk for Pulmonary Hypertension.
AB - BACKGROUND AND AIMS: Infants with Down syndrome (DS) or Trisomy 21, are at high
risk for developing pulmonary arterial hypertension (PAH), but mechanisms that
increase susceptibility are poorly understood. Laboratory studies have shown that
early disruption of angiogenesis during development impairs vascular and alveolar
growth and causes PAH. Human chromosome 21 encodes known anti-angiogenic factors,
including collagen18a1 (endostatin, ES), beta-amyloid peptide (BAP) and Down
Syndrome Critical Region 1 (DSCR-1). Therefore, we hypothesized that fetal lungs
from subjects with DS are characterized by early over-expression of anti
angiogenic factors and have abnormal lung vascular growth in utero. METHODS:
Human fetal lung tissue from DS and non-DS subjects were obtained from a
biorepository. Quantitative reverse transcriptase PCR (qRT-PCR) was performed to
assay 84 angiogenesis-associated genes and individual qRT-PCR was performed for
ES, amyloid protein precursor (APP) and DSCR1. Western blot analysis (WBA) was
used to assay lung ES, APP and DSCR-1 protein contents. Lung vessel density and
wall thickness were determined by morphometric analysis. RESULTS: The
angiogenesis array identified up-regulation of three anti-angiogenic genes:
COL18A1 (ES), COL4A3 (tumstatin) and TIMP3 (tissue inhibitor of metallopeptidase
3) in DS lungs. Single qRT-PCR and WBA showed striking elevations of ES and APP
mRNA (p = 0.022 and p = 0.001) and protein (p = 0.040 and p = 0.002;
respectively). Vessel density was reduced (p = 0.041) and vessel wall thickness
was increased in DS lung tissue (p = 0.033) when compared to non-DS subjects.
CONCLUSIONS: We conclude that lung anti-angiogenic factors, including COL18A1
(ES), COL4A3, TIMP3 and APP are over-expressed and fetal lung vessel growth is
decreased in subjects with DS. We speculate that increased fetal lung anti
angiogenic factor expression due to trisomy 21 impairs lung vascular growth and
signaling, which impairs alveolarization and contributes to high risk for PAH
during infancy.
PMID- 27487165
TI - Rhizosphere selection of Pseudomonas putida KT2440 variants with increased
fitness associated to changes in gene expression.
AB - As the interface between plant roots and soil, the rhizosphere is a complex
environment where nutrients released by the plant promote microbial growth.
Increasing evidences indicate that the plant also exerts a selective pressure on
microbial populations in the rhizosphere, favouring colonization by certain
groups. In this work, we have designed an experimental setup to begin analysing
the evolution of a specific bacterial population in the rhizosphere, using
Pseudomonas putida KT2440 as model organism. After several rounds of selection
without passage through laboratory growth conditions, derivatives of this strain
with increased fitness in the rhizosphere were isolated. Detailed analysis of one
of these clones indicated that this effect is specific for rhizosphere conditions
and derives from changes in its transcriptional profile in this environment, with
43 genes being differentially expressed with respect to the parental strain.
Several of these genes belong to functional categories which could affect stress
adaptation and availability of particular nutrients. By inactivating two genes
identified as upregulated in the selected clone (coding for a stress-response
protein and a rRNA modifying protein), these functions were shown to contribute
to rhizosphere fitness. Our data also suggest the existence of different
evolutionary pathways leading to increased rhizosphere fitness.
PMID- 27487166
TI - Construction of Electrochemical Chiral Interfaces with Integrated Polysaccharides
via Amidation.
AB - Polysaccharides of sodium carboxymethyl cellulose (CMC) and chitosan (CS) were
integrated together via amidation reactions between the carboxyl groups on sodium
CMC and the amino groups on CS. Compared with individual sodium CMC and CS, the
integrated polysaccharides with a mass ratio of 1:1, CMC-CS (1:1), exhibited a
three-dimensional (3D) porous network structure, resulting in a significantly
enhanced hydrophility due to the exposed polar functional groups in the CMC-CS
(1:1). Chiral interfaces were constructed with the integrated polysaccharides and
used for electrochemical enantiorecognition of tryptophan (Trp) isomers. The CMC
CS (1:1) chiral interfaces exhibited excellent selectivity toward the Trp isomers
owing to the highly hydrophilic feature of CMC-CS (1:1) and the different steric
hindrance during the formation of H bonds between Trp isomers and CMC-CS (1:1).
Also, the optimization in the preparation of integrated polysaccharides such as
mass ratio and combination mode (amidation or electrostatic interactions) was
investigated. The CMC-CS (1:1) presented the ability of determining the
percentage of d-Trp in racemic mixtures, and thus, the proposed electrochemical
chiral interfaces could be regarded as a potential biosensing platform for
enantiorecognition of chiral compounds.
PMID- 27487167
TI - Triacetonide of Glucoheptonic Acid in the Scalable Syntheses of d-Gulose, 6-Deoxy
d-gulose, l-Glucose, 6-Deoxy-l-glucose, and Related Sugars.
AB - Ease of separation of petrol-soluble acetonides derived from the triacetonide of
methyl glucoheptonate allows scalable syntheses of rare sugars containing the l
gluco or d-gulo structural motif with any oxidation level at the C6 or C1
position of the hexose, usually without chromatography: meso-d-glycero-d
guloheptitol available in two steps is an ideal entry point for the study of the
biotechnological production of heptoses.
PMID- 27487168
TI - Life dissatisfaction is associated with depression and poorer surgical outcomes
among lumbar spinal stenosis patients: a 10-year follow-up study.
AB - Life satisfaction is associated with overall somatic health and the short-term
surgical outcome in lumbar spinal stenosis (LSS) patients. In this study, the
long-term relationship between life satisfaction and the surgical outcome in LSS
patients was investigated in a 10-year follow-up. This prospective clinical study
included 102 LSS patients who underwent decompressive surgery. They completed a
set of questionnaires first preoperatively and then 6 times postoperatively (at 3
and 6 months, and at 1, 2, 5 and 10 years). The final study population at the 10
year follow-up comprised 72 patients. A four-item life satisfaction scale was
used to measure global life satisfaction. The sum of all seven life satisfaction
scores provided a measure of the life dissatisfaction burden over the entire 10
year follow-up. Depression was measured using the Beck Depression Inventory. The
surgical outcome was evaluated using the Oswestry Disability Index, pain
evaluation (visual analogue scale), self-reported walking capacity and overall
satisfaction with the surgery. Both preoperative life dissatisfaction and the
long-term life dissatisfaction burden were associated with poorer 10-year
surgical outcomes (i.e. Oswestry Disability Index and visual analogue scale) in
logistic regression analyses. Life dissatisfaction was also associated with
symptoms of depression. Monitoring subjective well-being, especially life
satisfaction and mood, in LSS patients before and after surgery may help in
detecting those at risk of a poorer long-term surgical outcome.
PMID- 27487169
TI - Rectal Indomethacin to Prevent Post-ERCP Pancreatitis.
PMID- 27487170
TI - Should We Still Administer Prophylactic Rectal NSAIDs to Average-Risk Patients
Undergoing ERCP?
PMID- 27487172
TI - Iron-Catalyzed Ortho C-H Methylation of Aromatics Bearing a Simple Carbonyl Group
with Methylaluminum and Tridentate Phosphine Ligand.
AB - Iron-catalyzed C-H functionalization of aromatics has attracted widespread
attention from chemists in recent years, while the requirement of an elaborate
directing group on the substrate has so far hampered the use of simple aromatic
carbonyl compounds such as benzoic acid and ketones, much reducing its synthetic
utility. We describe here a combination of a mildly reactive methylaluminum
reagent and a new tridentate phosphine ligand for metal catalysis, 4-(bis(2
(diphenylphosphanyl)phenyl)phosphanyl)-N,N-dimethylaniline (Me2N-TP), that allows
us to convert an ortho C-H bond to a C-CH3 bond in aromatics and heteroaromatics
bearing simple carbonyl groups under mild oxidative conditions. The reaction is
powerful enough to methylate all four ortho C-H bonds in benzophenone. The
reaction tolerates a variety of functional groups, such as boronic ester, halide,
sulfide, heterocycles, and enolizable ketones.
PMID- 27487171
TI - Production of Plasmodium vivax enolase in Escherichia coli and its protective
properties.
AB - Plasmodium vivax predominates in South-East Asia and the American continent,
causes significant morbidity and inflicts a huge socioeconomic burden. Sequencing
completion of the Plasmodium vivax genome and transcriptome provides the chance
to identify antigens. Enolase is the eighth enzyme in the glycolytic pathway,
which, apart from its glycolytic function, also possess antigenic properties and
is present on the cell wall of many invasive organisms, such as Candida albicans.
In order to assess whether enolase of Plasmodium vivax is also antigenic, in this
study, we first reported the expression and purification of recombinant
Plasmodium vivax enolase (r-Pven) in Escherichia coli, using prokaryotic
expression vector. The r-Pven was expressed in soluble form in E. coli, and the
expression was verified by SDS-PAGE and western blotting analysis. The r-Pven was
purified to 90% purity by nickel-nitrilotriacetic acid (Ni2+-NTA) resin
chromatography. For reactivity with r-Pven, compared with the average values of
the reactivity of control serum samples, the average values of the reactivity of
99 individual serums from vivax malaria patients appeared higher, and there was
significant difference between them (p=0.0117<0.05). Mice anti-r-Pven antibodies
inhibited the growth of in vitro cultures of P. falciparum. Mice immunized with r
Pven showed protection against a challenge with the mouse malarial parasite
Plasmodium berghei. The antibodies raised against r-Pven were specific for
Plasmodium and did not react to the host tissues. These observations established
Plasmodium vivax enolase to be a potential protective antigen.
PMID- 27487173
TI - Human papillomavirus in oropharyngeal cancer: The changing face of a disease.
AB - The last decade has brought about an unexpected rise in oropharyngeal squamous
cell carcinoma (OPSCC) primarily in white males from the ages of 40-55years, with
limited exposure to alcohol and tobacco. This subset of squamous cell carcinoma
(SCC) has been found to be associated with human papillomavirus infection (HPV).
Other Head and Neck Squamous Cell carcinoma (HNSCC) subtypes include oral cavity,
hypopharyngeal, nasopharyngeal, and laryngeal SCC which tend to be HPV negative.
HPV associated oropharyngeal cancer has proven to differ from alcohol and tobacco
associated oropharyngeal carcinoma in regards to the molecular pathophysiology,
presentation, epidemiology, prognosis, and improved response to chemoradiation
therapy. Given the improved survival of patients with HPV associated SCC, efforts
to de-intensify treatment to decrease treatment related morbidity are at the
forefront of clinical research. This review will focus on the important
differences between HPV and tobacco related oropharyngeal cancer. We will review
the molecular pathogenesis of HPV related oropharyngeal cancer with an emphasis
on new paradigms for screening and treating this disease.
PMID- 27487174
TI - An update on pharmacotherapy for personality disorders.
PMID- 27487175
TI - Red-Green-Blue Trichromophoric Nanoparticles with Dual Fluorescence Resonance
Energy Transfer: Highly Sensitive Fluorogenic Response Toward Polyanions.
AB - A red-green-blue (RGB) trichromophoric fluorescent organic nanoparticle
exhibiting multi-colour emission was constructed; the blue-emitting cationic
oligofluorene nanoparticle acted as an energy-donor scaffold to undergo
fluorescence resonance energy transfer (FRET) to a red-emitting dye embedded in
the nanoparticle (interior FRET) and to a green-emitting dye adsorbed on the
surface through electrostatic interactions (exterior FRET). Each FRET event
occurs independently and is free from sequential FRET, thus the resultant dual
FRET system exhibits multi-colour emission, including white, in aqueous solution
and film state. A characteristic white-emissive nanoparticle showed visible
responses upon perturbation of the exterior FRET efficiency by acceptor
displacement, leading to highly sensitive responses toward polyanions in a
ratiometric manner. Specifically, our system exhibits high sensitivity toward
heparin with an extremely low detection limit.
PMID- 27487176
TI - Exploratory Study of Heart Rate Variability and Sleep among Emergency Medical
Services Shift Workers.
AB - OBJECTIVES: To characterize the continuity and duration of sleep, and to measure
nocturnal cardiac autonomic balance via heart rate variability (HRV) in a group
of emergency medical technicians (EMTs) on and off duty. METHODS: Fourteen EMTs
completed an online, daily sleep log that recorded total sleep duration, bedtime,
rise time, and the number of alarms that caused awakening. HRV was captured using
a physiological status monitor (PSM) affixed to a chest strap during sleep.
RESULTS: For the 7-day trial, each of the 14 EMTs logged three work days (WDs)
and four non-work days (NWDs). They reported sleeping significantly fewer hours
per night on WDs (6.4 +/- 2.1) than on NWDs (7.9 +/- 0.5; P < 0.05), and
experienced more sleep disruptions on WDs (4.4 +/- 2.8) than on NWDs (1.3 +/-
2.2; P < 0.001) as measured by the number of alarms. Global and vagal indices of
HRV during sleep were significantly reduced during WDs (Standard Deviation of
Normal R-R Intervals (SDNN) = 43.4 +/- 2.0 ms and High Frequency (HF) = 24.3 +/-
1.2 ms2) when compared to NWDs (SDNN = 61.1 +/- 1.0 ms and HF = 42.7 +/- 1.5 ms2;
P < 0.001). CONCLUSION: EMTs who worked 24-hour shifts had shorter, more
fragmented sleep associated with greater cumulative exposure to increased
sympathetic and decreased parasympathetic activity as measured via sleep HRV.
These changes in cardiac autonomic tone constitute one plausible pathway through
which sleep deprivation may increase risk for cardiovascular disease.
PMID- 27487177
TI - Data-Driven Derivation of an "Informer Compound Set" for Improved Selection of
Active Compounds in High-Throughput Screening.
AB - Despite the usefulness of high-throughput screening (HTS) in drug discovery, for
some systems, low assay throughput or high screening cost can prohibit the
screening of large numbers of compounds. In such cases, iterative cycles of
screening involving active learning (AL) are employed, creating the need for
smaller "informer sets" that can be routinely screened to build predictive models
for selecting compounds from the screening collection for follow-up screens.
Here, we present a data-driven derivation of an informer compound set with
improved predictivity of active compounds in HTS, and we validate its benefit
over randomly selected training sets on 46 PubChem assays comprising at least
300,000 compounds and covering a wide range of assay biology. The informer
compound set showed improvement in BEDROC(alpha = 100), PRAUC, and ROCAUC values
averaged over all assays of 0.024, 0.014, and 0.016, respectively, compared to
randomly selected training sets, all with paired t-test p-values <10(-15). A per
assay assessment showed that the BEDROC(alpha = 100), which is of particular
relevance for early retrieval of actives, improved for 38 out of 46 assays,
increasing the success rate of smaller follow-up screens. Overall, we showed that
an informer set derived from historical HTS activity data can be employed for
routine small-scale exploratory screening in an assay-agnostic fashion. This
approach led to a consistent improvement in hit rates in follow-up screens
without compromising scaffold retrieval. The informer set is adjustable in size
depending on the number of compounds one intends to screen, as performance gains
are realized for sets with more than 3,000 compounds, and this set is therefore
applicable to a variety of situations. Finally, our results indicate that random
sampling may not adequately cover descriptor space, drawing attention to the
importance of the composition of the training set for predicting actives.
PMID- 27487178
TI - The Molecular Bronchoscope: A Tool for Measurement of Spatially Dependent CO2
Concentrations in the Lungs.
AB - Respiratory physicians use bronchoscopy for visual assessment of the lungs'
topography and collecting tissue samples for external analysis. We propose a
novel bronchoscope tool that would enable spatially dependent measurements of the
functioning of the lungs by determining local concentrations of carbon dioxide,
which will be produced by healthy parts of the lung at rates that are higher than
from portions where gas exchange is impaired. The gas analyzer is based on a
compact laser absorption spectrometer making use of fiber optics for delivery and
return of low intensity diode laser radiation to and from the measurement chamber
at the distal end of a flexible conduit. The appropriate optical wavelength was
chosen such that light is selectively absorbed only by gaseous CO2. The optical
absorption takes place over a short path (8.8 mm) within a rigid, 12 mm long,
perforated probe tip. Wavelength modulation spectroscopy was adopted as the
analytical technique to reduce the noise on the optical signal and yield
measurements of relative CO2 concentration every 180 ms with a precision as low
as 600 part-per-million by volume. The primary objective of such a device is to
see if additional spatial information about the lungs functionality can be
gathered, which will complement visual observation.
PMID- 27487179
TI - Improved method for assembly of hemeprotein neuronal NO-synthase heterodimers.
AB - The assembly of mutated and wild type monomers into functional heterodimeric
hemeproteins has provided important mechanistic insights. As in the case of NO
synthase (NOS), the existing methods to make such heterodimeric NOSs are
inefficient and labor intensive with typical yields of about 5%. We have found
that expression of neuronal NOS heterodimers in insect cells, where we take
advantage of an exogenous heme-triggered chaperone-assisted assembly process,
provides an approximately 43% yield in heterodimeric NOS. In contrast, in
Escherichia coli little heterodimerization occurred. Thus, insect cells are
preferred and may represent a valuable method for assembly of other dimeric
hemeproteins.
PMID- 27487180
TI - Rate and predictors of human papillomavirus vaccine uptake among women who have
sex with women in the United States, the National Health and Nutrition
Examination Survey, 2009-2012.
AB - AIMS AND OBJECTIVES: To examine rates and associated correlates of human
papilloma virus vaccine uptake in women who have sex with women in the United
States, and to determine whether they differ from those in women who do not have
sex with women. BACKGROUND: Women who have sex with women are at risk for human
papilloma virus infection but are less likely to receive preventive
gynaecological services. Little research has been carried out to evaluate human
papilloma virus vaccination rates and associated predictors of vaccination uptake
in this population. DESIGN: Cross-sectional descriptive study. METHODS: Data from
two consecutive cohorts of the National Health and Nutrition Examination Survey
conducted by the United States' Centers for Disease Control were analysed.
RESULTS: The sample (N = 1105) consisted of women aged 18-26 years. There was no
difference in human papilloma virus vaccine uptake between women who have sex
with women and women who do not have sex with women. Overall, the vaccination
rate was low (32.5%). Having health insurance and more education were significant
predictors of vaccine uptake in women who have sex with women. Higher education
and younger age were predictors in women who do not have sex with women.
CONCLUSIONS: Vaccination rates of women are far lower than the national target of
80%. The predictors of vaccine uptake were different in women who have sex with
women than for women who do not have sex with women. RELEVANCE TO CLINICAL
PRACTICE: Women in their 20s (regardless of their sexual orientation) should be
recognised as an undervaccinated population and require targeted interventions to
improve vaccination uptake.
PMID- 27487181
TI - Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the
Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis
Treatment Response.
AB - BACKGROUND: There is an urgent need for new tools for the early diagnosis of TB
disease and monitoring of the response to treatment, especially in resource
constrained settings. We investigated the usefulness of host markers detected in
saliva as candidate biomarkers for the immunological diagnosis of TB disease and
monitoring of treatment response. METHODS: We prospectively collected saliva
samples from 51 individuals that presented with signs and symptoms suggestive of
TB disease at a health centre in Cape Town, South Africa, prior to the
establishment of a clinical diagnosis. Patients were later classified as having
TB disease or other respiratory disease (ORD), using a combination of clinical,
radiological and laboratory findings. We evaluated the concentrations of 69 host
markers in saliva samples using a multiplex cytokine platform, and assessed the
diagnostic potentials of these markers by receiver operator characteristics (ROC)
curve analysis, and general discriminant analysis. RESULTS: Out of the 51 study
participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV
infected. Only two of the 69 host markers that were evaluated (IL-16 and IL-23)
diagnosed TB disease individually with area under the ROC curve >=0.70. A five
marker biosignature comprising of IL-1beta, IL-23, ECM-1, HCC1 and fibrinogen
diagnosed TB disease with a sensitivity of 88.9% (95% CI,76.7-99.9%) and
specificity of 89.7% (95% CI, 60.4-96.6%) after leave-one-out cross validation,
regardless of HIV infection status. Eight-marker biosignatures performed with a
sensitivity of 100% (95% CI, 83.2-100%) and specificity of 95% (95% CI, 68.1
99.9%) in the absence of HIV infection. Furthermore, the concentrations of 11 of
the markers changed during treatment, indicating that they may be useful in
monitoring of TB treatment response. CONCLUSION: We have identified novel
salivary biosignatures which may be useful in the diagnosis of TB disease and
monitoring of the response to TB treatment. Our findings require further
validation in larger studies before these biosignatures could be considered for
point-of-care screening test development.
PMID- 27487182
TI - TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2
Mediated Immunopathology.
AB - Persistent TH2 cytokine responses following chronic helminth infections can often
lead to the development of tissue pathology and fibrotic scarring. Despite a good
understanding of the cellular mechanisms involved in fibrogenesis, there are very
few therapeutic options available, highlighting a significant medical need and
gap in our understanding of the molecular mechanisms of TH2-mediated
immunopathology. In this study, we found that the Map3 kinase, TPL-2 (Map3k8;
Cot) regulated TH2-mediated intestinal, hepatic and pulmonary immunopathology
following Schistosoma mansoni infection or S. mansoni egg injection. Elevated
inflammation, TH2 cell responses and exacerbated fibrosis in Map3k8-/-mice was
observed in mice with myeloid cell-specific (LysM) deletion of Map3k8, but not
CD4 cell-specific deletion of Map3k8, indicating that TPL-2 regulated myeloid
cell function to limit TH2-mediated immunopathology. Transcriptional and
metabolic assays of Map3k8-/-M2 macrophages identified that TPL-2 was required
for lipolysis, M2 macrophage activation and the expression of a variety of genes
involved in immuno-regulatory and pro-fibrotic pathways. Taken together this
study identified that TPL-2 regulated TH2-mediated inflammation by supporting
lipolysis and M2 macrophage activation, preventing TH2 cell expansion and
downstream immunopathology and fibrosis.
PMID- 27487184
TI - Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe
in biorelevant media.
AB - The effects of different formulations and processes on inducing and maintaining
the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two
biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted
state simulated gastric fluid (FaSSGF) at different temperatures (25 degrees C
and 37 degrees C) were investigated in this work. Ternary solid dispersions of
EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using
melt-quenching and spray-drying methods. The resulting solid dispersions were
characterized using scanning electron microscopy, differential scanning
calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier
transformation infrared spectroscopy. The dissolution of all the ternary solid
dispersions was tested in vitro under non-sink conditions. All the prepared solid
dispersions were amorphous in nature. In FaSSIF at 25 degrees C, the melt
quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD)
solid dispersions and supersaturation was maintained. However, at 37 degrees C,
rapid and variable precipitation behavior was observed for all the MQ and SD
formulations. In FaSSGF, the melting method resulted in better solubility than
the spray-drying method at both temperatures. Ternary solid dispersions show
potential for improving solubility and supersaturation. However, powder
dissolution experiments of these solid dispersions of EZ at 25 degrees C may not
predict the supersaturation behavior at physiologically relevant temperatures.
PMID- 27487183
TI - Self-Reported Health Experiences of Children Living with Congenital Heart
Defects: Including Patient-Reported Outcomes in a National Cohort Study.
AB - BACKGROUND: Understanding children's views about living with congenital heart
defects (CHDs) is fundamental to supporting their successful participation in
daily life, school and peer relationships. As an adjunct to a health and quality
of life outcomes questionnaire, we asked school-age children who survived infant
heart procedures to describe their experiences of living with CHDs. METHODS: In a
UK-wide cohort study, children aged 10 to 14 years with CHDs self-completed
postal questionnaires that included an open question about having a 'heart
problem'. We compared the characteristics of children with more and less severe
cardiac diagnoses and, through collaborative inductive content analysis,
investigated the subjective experiences and coping strategies described by
children in both clinical severity groups. RESULTS: Text and/or drawings were
returned by 436 children (246 boys [56%], mean age 12.1 years [SD 1.0; range 10
14]); 313 had less severe (LS) and 123 more severe (MS) cardiac diagnoses. At the
most recent hospital visit, a higher proportion of the MS group were underweight
(more than two standard deviations below the mean for age) or cyanosed
(underweight: MS 20.0%, LS 9.9%; cyanosed: MS 26.2%, LS 3.5%). Children in the MS
group described concerns about social isolation and feeling 'different', whereas
children with less severe diagnoses often characterised their CHD as 'not a big
thing'. Some coping strategies were common to both severity groups, including
managing health information to avoid social exclusion, however only children in
the LS group considered their CHD 'in the past' or experienced a sense of
survivorship. CONCLUSIONS: Children's reported experiences were not dependent on
their cardiac diagnosis, although there were clear qualitative differences by
clinical severity group. Children's concerns emphasised social participation and
our findings imply a need to shift the clinical focus from monitoring cardiac
function to optimising participation. We highlight the potential for informing
and evaluating clinical practice and service provision through seeking patient
reported outcomes in paediatric care.
PMID- 27487186
TI - Ongoing Clinical Trials in Prostate Cancer: The STAMPEDE Trial.
PMID- 27487185
TI - Errors and Nonadherence in Pediatric Oral Chemotherapy Use.
AB - BACKGROUND: Nonadherence and medication error both limit the effectiveness of
oral chemotherapy. The overlap between nonadherence and medication error is not
well studied in children, and interventions strategies differ for each. Our
objective was to describe nonadherence and errors in children with cancer to
inform future interventions. METHODS: Nonadherence was measured using two self
report tools. Medication error was measured using medication review and
observation of administration at home. Two clinicians made judgments about
whether each error also represented an episode of nonadherence. RESULTS: Of 72
errors detected in 92 home visits, 27 were also instances of nonadherence. For
example, parents gave a child 1 tablet of mercaptopurine every day rather than
the prescribed 1 tablet 5 days a week and 1/2 tablet on weekends. Clinician
reviewers judged that family interventions and health system interventions would
be most effective in preventing the errors and nonadherence identified in this
population of children with cancer. DISCUSSION: The relationship between
medication errors and nonadherence is not well described in the literature. Our
data indicate that medication error and nonadherence coexist in the same
population and in the same patient. Interventions should address both to most
effectively support self-management.
PMID- 27487188
TI - Evidence for Ventilation through Collective Respiratory Movements in Giant
Honeybee (Apis dorsata) Nests.
AB - The Asian giant honeybees (Apis dorsata) build single-comb nests in the open,
which makes this species particularly susceptible to environmental strains. Long
term infrared (IR) records documented cool nest regions (CNR) at the bee curtain
(nCNR = 207, nnests > 20) distinguished by marked negative gradients (DeltaTCNR/d
< -3 degrees C / 5 cm) at their margins. CNRs develop and recede within minutes,
predominantly at higher ambient temperatures in the early afternoon. The
differential size (DeltaACNR) and temperature (DeltaTCNR) values per time unit
correlated mostly positively (RAT > 0) displaying the Venturi effect, which
evidences funnel properties of CNRs. The air flows inwards through CNRs, which is
verified by the negative spatial gradient DeltaTCNR/d, by the positive grading of
TCNR with Tamb and lastly by fanners which have directed their abdomens towards
CNRs. Rare cases of RAT < 0 (< 3%) document closing processes (for
DeltaACNR/Deltat < -0.4 cm2/s) but also suggest ventilation of the bee curtain
(for DeltaACNR/Deltat > +0.4 cm2/s) displaying "inhalation" and "exhalation"
cycling. "Inhalation" could be boosted by bees at the inner curtain layers, which
stretch their extremities against the comb enlarging the inner nest lumen and
thus causing a pressure fall which drives ambient air inwards through CNR
funnels. The relaxing of the formerly "activated" bees could then trigger the
"exhalation" process, which brings the bee curtain, passively by gravity, close
to the comb again. That way, warm, CO2-enriched nest-borne air is pressed
outwards through the leaking mesh of the bee curtain. This ventilation hypothesis
is supported by IR imaging and laser vibrometry depicting CNRs in at least four
aspects as low-resistance convection funnels for maintaining thermoregulation and
restoring fresh air in the nest.
PMID- 27487187
TI - Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and
Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism:
Systematic Review and Network Meta-Analysis.
AB - BACKGROUND: Historically, warfarin or aspirin have been the recommended
therapeutic options for the extended treatment (>3 months) of VTE. Data from
Phase III randomised controlled trials (RCTs) are now available for non-VKA oral
anticoagulants (NOACs) in this indication. The current systematic review and
network meta-analysis (NMA) were conducted to compare the efficacy and safety of
anticoagulants for the extended treatment of VTE. METHODS: Electronic databases
(accessed July 2014 and updated April 2016) were systematically searched to
identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban,
and warfarin for the extended treatment of VTE. Eligible studies included adults
with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A
fixed-effect Bayesian NMA was conducted, and results were presented as relative
risks (RRs). Sensitivity analyses examining (i) the dataset employed according to
the time frame for outcome assessment (ii) the model used for the NMA were
conducted. RESULTS: Eleven Phase III RCTs (examining apixaban, aspirin,
dabigatran, rivaroxaban, warfarin and placebo) were included. The risk of the
composite efficacy outcome (VTE and VTE-related death) was statistically
significantly lower with the NOACs and warfarin INR 2.0-3.0 compared with
aspirin, with no significant differences between the NOACs. Treatment with
apixaban (RR 0.23, 95% CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43,
0.71) was associated with a statistically significantly reduced risk of 'major or
clinically relevant non-major bleed' compared with warfarin INR 2.0-3.0. Apixaban
also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95%
Crl 0.18, 0.97) and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity
analyses indicate that results were dependent on the dataset, but not on the type
of NMA model employed. CONCLUSIONS: Results from the NMA indicate that NOACs are
an effective treatment for prevention of VTE or VTE-related death) in the
extended treatment setting. However, bleeding risk differs between potential
treatments, with apixaban reporting the most favourable profile compared with
other NOACs, warfarin INR 2.0-3.0, and aspirin.
PMID- 27487189
TI - Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis
Treatment.
AB - OBJECTIVE: To determine the case-fatality rate (CFR) at the end of the intensive
phase of tuberculosis (TB) treatment, and factors associated with fatality.
METHODS: TB patients diagnosed between 2006 and 2013 were followed-up during
treatment. We computed the CFR at the end of the intensive phase of TB treatment,
and the incidence of death per 100 person-days (pd) of follow-up. We performed
survival analysis using the Kaplan-Meier method and Cox regression, and calculate
hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 5,182
patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%)
occurred during the intensive phase of treatment, with a CFR of 1.7%. The
incidence of death was 0.028/100 pd. The following factors were associated with
death during the intensive phase: being >50 years (HR = 36.9;CI:4.8-283.4); being
retired (HR = 2.4;CI:1.1-5.1); having visited the emergency department (HR =
3.1;CI:1.2-7.7); HIV infection (HR = 3.4;CI:1.6-7.2); initial standard treatment
with 3 drugs (HR = 2.0;CI:1.2-3.3) or non-standard treatments (HR = 2.68;CI:1.36
5.25); comprehension difficulties (HR = 2.8;CI:1.3-6.1); and smear-positive
sputum (HR = 2.3-CI:1.0-4.8). CONCLUSION: There is a non-negligible CFR during
the intensive phase of TB, whose reduction should be prioritised. The CFR could
be a useful indicator for evaluating TB programs.
PMID- 27487190
TI - Quality Improvement in Acute Ischemic Stroke Care in Taiwan: The Breakthrough
Collaborative in Stroke.
AB - In the management of acute ischemic stroke, guideline adherence is often
suboptimal, particularly for intravenous thrombolysis or anticoagulation for
atrial fibrillation. We sought to improve stroke care quality via a collaborative
model, the Breakthrough Series (BTS)-Stroke activity, in a nationwide, multi
center activity in Taiwan. A BTS Collaborative, a short-term learning system for
a large number of multidisciplinary teams from hospitals, was applied to enhance
acute ischemic stroke care quality. Twenty-four hospitals participated in and
submitted data for this stroke quality improvement campaign in 2010-2011.
Totally, 14 stroke quality measures, adopted from the Get With The Guideline
(GWTG)-Stroke program, were used to evaluate the performance and outcome of the
ischemic stroke patients. Data for a one-year period from 24 hospitals with
13,181 acute ischemic stroke patients were analyzed. In 14 hospitals, most stroke
quality measures improved significantly during the BTS-activity compared with a
pre-BTS-Stroke activity period (2006-08). The rate of intravenous thrombolysis
increased from 1.2% to 4.6%, door-to-needle time <=60 minutes improved from 7.1%
to 50.8%, symptomatic hemorrhage after intravenous thrombolysis decreased from
11.0% to 5.6%, and anticoagulation therapy for atrial fibrillation increased from
32.1% to 64.1%. The yearly composite measures of five stroke quality measures
revealed significant improvements from 2006 to 2011 (75% to 86.3%, p<0.001). The
quarterly composite measures also improved significantly during the BTS-Stroke
activity. In conclusion, a BTS collaborative model is associated with improved
guideline adherence for patients with acute ischemic stroke. GWTG-Stroke
recommendations can be successfully applied in countries besides the United
States.
PMID- 27487191
TI - Risk-Reduction Program for Cardiovascular and Limb Events in Patients With
Peripheral Arterial Disease-Reply.
PMID- 27487192
TI - Field-induced doping-mediated tunability in work function of Al-doped ZnO: Kelvin
probe force microscopy and first-principle theory.
AB - We demonstrate that the work function of Al-doped ZnO (AZO) can be tuned
externally by applying an electric field. Our experimental investigations using
Kelvin probe force microscopy show that by applying a positive or negative tip
bias, the work function of AZO film can be enhanced or reduced, which
corroborates well with the observed charge transport using conductive atomic
force microscopy. These findings are further confirmed by calculations based on
first-principles theory. Tuning the work function of AZO by applying an external
electric field is not only important to control the charge transport across it,
but also to design an Ohmic contact for advanced functional devices.
PMID- 27487193
TI - Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention
Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral
System (OROS) Methylphenidate With a Goal of Symptom Remission.
AB - OBJECTIVE: To evaluate the efficacy and safety of individualized dosing within
the approved dose range for osmotic-release oral system (OROS) methylphenidate
hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD).
METHODS: A double-blind, 6-week trial was conducted between July 2009 and
February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a
screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly
assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could
be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was
achieved. AISRS score changes from baseline to end point (primary outcome) were
analyzed using analysis of covariance. RESULTS: At baseline, the intent-to-treat
population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8
years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0
(7.51), respectively. OROS methylphenidate-treated subjects exhibited a
significantly greater mean (SD) AISRS score improvement than placebo subjects (
17.1 [12.44] vs -11.7 [13.30]; P < .001). In general, OROS methylphenidate
treated subjects experienced greater improvements than placebo subjects in
secondary measures of symptom frequency, cognitive function, work productivity,
and quality-of-life. Little effect of OROS methylphenidate was observed in
exploratory sleep assessments. The adverse event pattern was similar to previous
reports of stimulants in adults with ADHD. CONCLUSIONS: OROS methylphenidate
treatment with individualized doses titrated to achieve symptom remission
demonstrated greater ADHD symptom reduction than placebo treatment. These data
support the overall efficacy of OROS methylphenidate treatment in the management
of adults with ADHD and provide new possibilities for additional intervention.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00937040.
PMID- 27487194
TI - What Is True Halving in the Payoff Matrix of Game Theory?
AB - In game theory, there are two social interpretations of rewards (payoffs) for
decision-making strategies: (1) the interpretation based on the utility criterion
derived from expected utility theory and (2) the interpretation based on the
quantitative criterion (amount of gain) derived from validity in the empirical
context. A dynamic decision theory has recently been developed in which dynamic
utility is a conditional (state) variable that is a function of the current
wealth of a decision maker. We applied dynamic utility to the equal division in
dove-dove contests in the hawk-dove game. Our results indicate that under the
utility criterion, the half-share of utility becomes proportional to a player's
current wealth. Our results are consistent with studies of the sense of fairness
in animals, which indicate that the quantitative criterion has greater validity
than the utility criterion. We also find that traditional analyses of repeated
games must be reevaluated.
PMID- 27487195
TI - Effect of Inorganic and Organic Carbon Enrichments (DIC and DOC) on the
Photosynthesis and Calcification Rates of Two Calcifying Green Algae from a
Caribbean Reef Lagoon.
AB - Coral reefs worldwide are affected by increasing dissolved inorganic carbon (DIC)
and organic carbon (DOC) concentrations due to ocean acidification (OA) and
coastal eutrophication. These two stressors can occur simultaneously,
particularly in near-shore reef environments with increasing anthropogenic
pressure. However, experimental studies on how elevated DIC and DOC interact are
scarce and fundamental to understanding potential synergistic effects and
foreseeing future changes in coral reef function. Using an open mesocosm
experiment, the present study investigated the impact of elevated DIC (pHNBS: 8.2
and 7.8; pCO2: 377 and 1076 MUatm) and DOC (added as 833 MUmol L-1 of glucose) on
calcification and photosynthesis rates of two common calcifying green algae,
Halimeda incrassata and Udotea flabellum, in a shallow reef environment. Our
results revealed that under elevated DIC, algal photosynthesis decreased
similarly for both species, but calcification was more affected in H. incrassata,
which also showed carbonate dissolution rates. Elevated DOC reduced
photosynthesis and calcification rates in H. incrassata, while in U. flabellum
photosynthesis was unaffected and thalus calcification was severely impaired. The
combined treatment showed an antagonistic effect of elevated DIC and DOC on the
photosynthesis and calcification rates of H. incrassata, and an additive effect
in U. flabellum. We conclude that the dominant sand dweller H. incrassata is more
negatively affected by both DIC and DOC enrichments, but that their impact could
be mitigated when they occur simultaneously. In contrast, U. flabellum can be
less affected in coastal eutrophic waters by elevated DIC, but its contribution
to reef carbonate sediment production could be further reduced. Accordingly,
while the capacity of environmental eutrophication to exacerbate the impact of OA
on algal-derived carbonate sand production seems to be species-specific,
significant reductions can be expected under future OA scenarios, with important
consequences for beach erosion and coastal sediment dynamics.
PMID- 27487196
TI - Diurnal changes in the histone H3 signature H3K9ac|H3K27ac|H3S28p are associated
with diurnal gene expression in Arabidopsis.
AB - Post-translational chromatin modifications are an important regulatory mechanism
in light signalling and circadian clock function. The regulation of diurnal
transcript level changes requires fine-tuning of the expression of generally
active genes depending on the prevailing environmental conditions. We
investigated the association of histone modifications H3K4me3, H3K9ac, H3K9me2,
H3S10p, H3K27ac, H3K27me3 and H3S28p with diurnal changes in transcript
expression using chromatin immunoprecipitations followed by sequencing (ChIP-Seq)
in fully expanded leaves 6 of Arabidopsis thaliana grown in short-day optimal and
water-deficit conditions. We identified a differential H3K9ac, H3K27ac and H3S28p
signature between end-of-day and end-of-night that is correlated with changes in
diurnal transcript levels. Genes with this signature have particular over
represented promoter elements and encode proteins that are significantly enriched
for transcription factors, circadian clock and starch catabolic process.
Additional activating modifications were prevalent in optimally watered (H3S10p)
and in water-deficit (H3K4me3) plants. The data suggest a mechanism for diurnal
transcript level regulation in which reduced binding of repressive transcription
factors facilitates activating H3K9ac, H3K27ac and H3S28p chromatin
modifications. The presence of activating chromatin modification patterns on
genes only at times of the day when their expression is required can explain why
some genes are differentially inducible during the diurnal cycle.
PMID- 27487197
TI - Alcohol Use Severity and Sexual Risk Behavior Among Female Substance Users.
AB - BACKGROUND: Substance use has been identified as one of the leading factors
related to HIV transmission in the United States. The association of problematic
drinking with sexual risk behavior puts individuals at greater risk for HIV
transmission. This may be of particular concern for women given that
approximately 66% of new HIV infections occurring through heterosexual
transmission are female. OBJECTIVES: To investigate alcohol use severity and
sexual risk behavior among females who use heavy, illicit drugs. METHODS: Female
substances users (N = 251; Mage = 31.90, SD = 7.67; 63.7% Black) self-reported
past month alcohol use and lifetime sexual risk behaviors with both casual and
steady sex partners. RESULTS: Problematic alcohol users were more likely to use
noninjection drugs and less likely to use injection drugs than abstainers and
more likely than moderate alcohol users to use alcohol before/during sex with a
steady partner. White problematic alcohol users were less likely to use injection
drugs before/during sex with a steady partner than abstainers. Black problematic
alcohol users were more likely to use non-injection and alcohol than moderate
alcohol users before/during sex with steady partners. CONCLUSIONS: The current
study extends the existing literature by taking a closer look at the role of
alcohol use severity in sexual risk taking behavior of Black and White female
substance users, a particularly vulnerable group for HIV transmission.
PMID- 27487198
TI - Single-Molecule Observation Reveals Spontaneous Protein Dynamics in the
Nucleosome.
AB - Structural dynamics of a protein molecule is often critical to its function.
Single-molecule methods provide efficient ways to investigate protein dynamics,
although it is very challenging to achieve a millisecond or higher temporal
resolution. Here we report spontaneous structural dynamics of the histone protein
core in the nucleosome based on a single-molecule method that can reveal
submillisecond dynamics by combining maximum likelihood estimation and
fluorescence correlation spectroscopy. The nucleosome, comprising ~147 bp DNA and
an octameric histone protein core consisting of H2A, H2B, H3, and H4, is the
fundamental packing unit of the eukaryotic genome. The nucleosome imposes a
physical barrier that should be overcome during various DNA-templated processes.
Structural fluctuation of the nucleosome in the histone core has been
hypothesized to be required for nucleosome disassembly but has yet to be directly
probed. Our results indicate that at 100 mM NaCl the histone H2A-H2B dimer
dissociates from the histone core transiently once every 3.6 +/- 0.6 ms and
returns to its position within 2.0 +/- 0.3 ms. We also found that the motion is
facilitated upon H3K56 acetylation and inhibited upon replacing H2A with H2A.Z.
These results provide the first direct examples of how a localized post
translational modification or an epigenetic variation affects the kinetic and
thermodynamic stabilities of a macromolecular protein complex, which may directly
contribute to its functions.
PMID- 27487199
TI - Targeting CYP51 for drug design by the contributions of molecular modeling.
AB - CYP51 is an enzyme of sterol biosynthesis pathway present in animals, plants,
protozoa and fungi. This enzyme is described as an important drug target that is
still of interest. Therefore, in this work, we reviewed the structure and
function of CYP51 and explored the molecular modeling approaches for the
development of new antifungal and antiprotozoans that target this enzyme.
Crystallographic structures of CYP51 of some organisms have already been
described in the literature, which enable the construction of homology models of
other organisms' enzymes and molecular docking studies of new ligands. The
binding mode and interactions of some new series of azoles with antifungal or
antiprotozoan activities has been studied and showed important residues of the
active site. Molecular modeling is an important tool to be explored for the
discovery and optimization of CYP51 inhibitors with better activities,
pharmacokinetics, and toxicological profiles.
PMID- 27487200
TI - Proteasomal Dysfunction Induced By Diclofenac Engenders Apoptosis Through
Mitochondrial Pathway.
AB - Diclofenac is the most commonly used phenylacetic acid derivative non-steroidal
anti-inflammatory drug (NSAID) that demonstrates significant analgesic,
antipyretic, and anti-inflammatory effects. Several epidemiological studies have
demonstrated anti-proliferative activity of NSAIDs and examined their apoptotic
induction effects in different cancer cell lines. However, the precise molecular
mechanisms by which these pharmacological agents induce apoptosis and exert anti
carcinogenic properties are not well known. Here, we have observed that
diclofenac treatment induces proteasome malfunction and promotes accumulation of
different critical proteasome substrates, including few pro-apoptotic proteins in
cells. Exposure of diclofenac consequently elevates aggregation of various
ubiquitylated misfolded proteins. Finally, we have shown that diclofenac
treatment promotes apoptosis in cells, which could be because of mitochondrial
membrane depolarization and cytochrome c release into cytosol. This study
suggests possible beneficial insights of NSAIDs-induced apoptosis that may
improve our existing knowledge in anti-proliferative interspecific strategies
development. J. Cell. Biochem. 118: 1014-1027, 2017. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27487201
TI - [Not Available].
PMID- 27487202
TI - Airborne PCB patterns and urban scale in the Southern Rio de la Plata Basin,
Argentina.
AB - Atmospheric Polychlorinated Biphenyls (PCBs: ? 42 congeners) collected by
polyurethane passive samplers (PAS-PUFs) in 29 stations from July 2010 to
February 2014 (n=141) in the most productive and populated Southern Rio de la
Plata area in Argentina were evaluated to assess concentration gradients,
potential sources and compositional profiles related to different land use and
urbanization. On a global scale, total airborne PCBs concentrations are low/very
low (below detection limit to 937pgm-3) and show a significant potential
correlation with urban scale increasing 2.5 times each 10 times increase of
population reflecting the primary role of urbanization controlling PCB emissions.
Compositional patterns evaluated by principal component analysis (PCA) of
individual congeners indicated that highly populated atmospheres are enriched in
lighter, more volatile tri, tetra and penta chlorine congeners of lighter Aroclor
mixtures (from 1242 to 1254) suggesting actual emission of fresh PCBs signatures
from sealants, combustion and/or electrical equipment. Sub urban and rural sites
show a gradual transition to heavier Aroclor mixtures (from 1254 to 1260) with
predominance of more persistent hexa and hepta PCBs indicating an aged background
signal resulting from long range transport and/or re-emission from historic
reservoirs such as soils.
PMID- 27487203
TI - Mechanistic Insights into Catalytic Ethanol Steam Reforming Using Isotope-Labeled
Reactants.
AB - The low-temperature ethanol steam reforming (ESR) reaction mechanism over a
supported Rh/Pt catalyst has been investigated using isotope-labeled EtOH and H2
O. Through strategic isotope labeling, all nonhydrogen atoms were distinct from
one another, and allowed an unprecedented level of understanding of the dominant
reaction pathways. All combinations of isotope- and non-isotope-labeled atoms
were detected in the products, thus there are multiple pathways involved in H2 ,
CO, CO2 , CH4 , C2 H4 , and C2 H6 product formation. Both the recombination of C
species on the surface of the catalyst and preservation of the C-C bond within
ethanol are responsible for C2 product formation. Ethylene is not detected until
conversion drops below 100 % at t=1.25 h. Also, quantitatively, 57 % of the
observed ethylene is formed directly through ethanol dehydration. Finally there
is clear evidence to show that oxygen in the SiO2 -ZrO2 support constitutes 10 %
of the CO formed during the reaction.
PMID- 27487204
TI - Recombinant expression of porcine lactoferrin peptide LF-6 with intein technology
and its immunomodulatory function in ETEC K88-infected mice.
AB - LF-6 is a modified antibacterial peptide derived from LFP-20, a major active
ingredient of porcine lactoferrin, whose antibacterial activity is 200 times
higher than its native protein counterpart. Moreover, LF-6 displays even higher
antibacterial activity than LFP-20 and negligible toxic adverse effects, make it
a potential therapeutic agent for antibacterial purposes. Escherichia coli
expression system has been a preferred choice and workhorse for most recombinant
proteins. However, LF-6 must be coexpressed with a fusion partner to avoid its
potentially fatal toxicity which would threat E. coli expression system. In this
study, we successfully introduced intein system to solve this problem, which LF-6
was N-terminally fused to dithiothreitol (DTT)-induced self-cleavable intein, and
it conduct cleavage when the intein-fusion peptide passing through a
chromatography column filled with chitin, then the spliced peptide was purified
with RP-HPLC and identified with mass spectroscopy. A bacteriostatic test showed
that the recombinant LF-6 displayed nearly the same antibacterial activity as the
chemically synthetized LF-6, and an in vivo immunoprotection analysis showed that
the recombinant LF-6 exerted protective effects on Escherichia coli (ETEC)-K88
infected mice, which significantly reduced the pro-inflammatory cytokines level
in plasma and intestine, and resistant to intestinal mucosal injury compared to
the infective alone groups. Our study indicates that the intein system allows a
safe and efficient method to produce recombinant LF-6, which not only has
antibacterial activity, but more importantly, has an immunomodulatory function.
PMID- 27487205
TI - MRI evaluation of benign prostatic hyperplasia: Correlation with international
prostate symptom score.
AB - PURPOSE: To investigate the correlation between magnetic resonance imaging (MRI)
derived prostate parameters and benign prostatic hyperplasia (BPH) type with the
International Prostate Symptom Score (IPSS). MATERIALS AND METHODS: In all, 61
patients (median age, 60; range, 41-81 years) who underwent preoperative MRI and
prostatectomy were included in this retrospective study. The MRI-based parameters
including total prostate volume (TPV), transition zone (TZ) volume (TZV), TZ
index, intravesical prostatic protrusion (IPP), the anterior fibromuscular stroma
(AFMS) distance, prostatic urethral angle, bladder wall thickness, urethral wall
thickness, urethral compression, urethral wall changes, and BPH type were
correlated with total IPSS, IPSS-storage symptom (IPSS-ss), IPSS-voiding symptom
(IPSS-vs), and responses to the individual IPSS questions using Spearman (rho) or
Pearson (r) correlation coefficients, one-way analysis of variance (ANOVA), and
multiple linear regression. RESULTS: TPV (r = 0.414, P = 0.001), TZV (r = 0.405,
P = 0.001), IPP (r = 0.270, P = 0.04), and AFMS distance (r = 0.363, P = 0.004)
correlated with total IPSS. In multiple linear regression analysis, TZV was the
only predictor for total IPSS (P = 0.001), IPSS-ss (P < 0.001), IPSS-vs (P =
0.03), and the scores for the IPSS questions 1 (P = 0.03) and 4 (P = 0.001). TPV
was a predictor of the scores for questions 2 (P = 0.003), 3 (P = 0.009), and 7
(P < 0.001). CONCLUSION: Several MRI-derived prostate measurements (TPV, TZV,
IPP, AFMS distance) correlated with total IPSS. TZV was the only predictor for
total IPSS based on multiple regression analysis. LEVEL OF EVIDENCE: 3 J. Magn.
Reson. Imaging 2017;45:917-925.
PMID- 27487206
TI - Heat Generation and Efficiency of a New Modified Phaco Tip and Sleeve.
AB - PURPOSE: To compare a modified phacoemulsification tip with the established micro
tip, in terms of temperature at the corneal wound, efficiency, and chatter
events, using the Centurion(r) Vision system. METHODS: Eighty porcine eyes were
randomized into 4 groups: 1)sleeveless conventional 45D MiniFlared ABS(r) Kelman
tip (1.1-mm incision); 2)sleeveless new modified 45D ABS(r) INTREPID(r) balanced
tip(1.1-mm incision); 3) Kelman tip with own sleeve (2.2-mm incision); 4)Balanced
tip with modified 4-rib sleeve (2.2-mm incision). Measurements were taken with 2
settings: longitudinal(power 40% and 70%) and torsional mode (power 40% and
100%). Peak temperatures were measured 0, 10, 30, and 60 seconds after continuous
ultrasound power. For the efficiency test, porcine lens nuclei were formalin
soaked and cut into 2.0 mm3 cubes. Efficiency and chatter were examined. RESULTS:
In all longitudinal settings, the sleeveless groups(1 and 2) showed lower
temperatures than the sleeved groups(3 and 4) (P = 0.003). In 100% torsional
mode, groups 3 and 4 produced significantly different temperatures(37.13 +/- 1.44
and 35.14 +/- 0.54, respectively; P = 0.007).The efficiency, in a 100% power
torsional setting, was13.52 +/- 2.60 sec for group 4, and 44.45+/- 14.75 sec for
group 3 (P<0.001). CONCLUSIONS: The two different bare tips show no significant
differences in thermogenesis. However, the balanced tip with sleeve produces
lower temperaturesat100% torsional power and better efficiency than the Kelman
tip.
PMID- 27487208
TI - Cancer: Fat and the fate of pancreatic tumours.
PMID- 27487207
TI - SAR11 bacteria linked to ocean anoxia and nitrogen loss.
AB - Bacteria of the SAR11 clade constitute up to one half of all microbial cells in
the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum
zones (OMZs), where oxygen falls below detection and anaerobic microbes have
vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism
has not yet been observed in SAR11, and it remains unknown how these bacteria
contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells
from the world's largest OMZ revealed previously uncharacterized SAR11 lineages
with adaptations for life without oxygen, including genes for respiratory nitrate
reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins
catalysing the nitrite-producing first step of denitrification and constituted
~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of
maximum nitrate reduction activity. These results link SAR11 to pathways of ocean
nitrogen loss, redefining the ecological niche of Earth's most abundant
organismal group.
PMID- 27487209
TI - Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV
susceptibility.
AB - Genetic differences that specify unique aspects of human evolution have typically
been identified by comparative analyses between the genomes of humans and closely
related primates, including more recently the genomes of archaic hominins. Not
all regions of the genome, however, are equally amenable to such study. Recurrent
copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1%
of cases of autism and is mediated by a complex set of segmental duplications,
many of which arose recently during human evolution. Here we reconstruct the
evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a
gene duplicated exclusively in Homo sapiens. We estimate that a 95-kilobase-pair
segment containing BOLA2 duplicated across the critical region approximately 282
thousand years ago (ka), one of the latest among a series of genomic changes that
dramatically restructured the locus during hominid evolution. All humans examined
carried one or more copies of the duplication, which nearly fixed early in the
human lineage--a pattern unlikely to have arisen so rapidly in the absence of
selection (P < 0.0097). We show that the duplication of BOLA2 led to a novel,
human-specific in-frame fusion transcript and that BOLA2 copy number correlates
with both RNA expression (r = 0.36) and protein level (r = 0.65), with the
greatest expression difference between human and chimpanzee in experimentally
derived stem cells. Analyses of 152 patients carrying a chromosome 16p11.
rearrangement show that more than 96% of breakpoints occur within the H. sapiens
specific duplication. In summary, the duplicative transposition of BOLA2 at the
root of the H. sapiens lineage about 282 ka simultaneously increased copy number
of a gene associated with iron homeostasis and predisposed our species to
recurrent rearrangements associated with disease.
PMID- 27487210
TI - Mechanism of arginine sensing by CASTOR1 upstream of mTORC1.
AB - The mechanistic Target of Rapamycin Complex 1 (mTORC1) is a major regulator of
eukaryotic growth that coordinates anabolic and catabolic cellular processes with
inputs such as growth factors and nutrients, including amino acids. In mammals
arginine is particularly important, promoting diverse physiological effects such
as immune cell activation, insulin secretion, and muscle growth, largely mediated
through activation of mTORC1 (refs 4, 5, 6, 7). Arginine activates mTORC1
upstream of the Rag family of GTPases, through either the lysosomal amino acid
transporter SLC38A9 or the GATOR2-interacting Cellular Arginine Sensor for mTORC1
(CASTOR1). However, the mechanism by which the mTORC1 pathway detects and
transmits this arginine signal has been elusive. Here, we present the 1.8 A
crystal structure of arginine-bound CASTOR1. Homodimeric CASTOR1 binds arginine
at the interface of two Aspartate kinase, Chorismate mutase, TyrA (ACT) domains,
enabling allosteric control of the adjacent GATOR2-binding site to trigger
dissociation from GATOR2 and downstream activation of mTORC1. Our data reveal
that CASTOR1 shares substantial structural homology with the lysine-binding
regulatory domain of prokaryotic aspartate kinases, suggesting that the mTORC1
pathway exploited an ancient, amino-acid-dependent allosteric mechanism to
acquire arginine sensitivity. Together, these results establish a structural
basis for arginine sensing by the mTORC1 pathway and provide insights into the
evolution of a mammalian nutrient sensor.
PMID- 27487211
TI - Thirst neurons anticipate the homeostatic consequences of eating and drinking.
AB - Thirst motivates animals to drink in order to maintain fluid balance. Thirst has
conventionally been viewed as a homeostatic response to changes in blood volume
or tonicity. However, most drinking behaviour is regulated too rapidly to be
controlled by blood composition directly, and instead seems to anticipate
homeostatic imbalances before they arise. How this is achieved remains unknown.
Here we reveal an unexpected role for the subfornical organ (SFO) in the
anticipatory regulation of thirst in mice. By monitoring deep-brain calcium
dynamics, we show that thirst-promoting SFO neurons respond to inputs from the
oral cavity during eating and drinking and then integrate these inputs with
information about the composition of the blood. This integration allows SFO
neurons to predict how ongoing food and water consumption will alter fluid
balance in the future and then to adjust behaviour pre-emptively. Complementary
optogenetic manipulations show that this anticipatory modulation is necessary for
drinking in several contexts. These findings provide a neural mechanism to
explain longstanding behavioural observations, including the prevalence of
drinking during meals, the rapid satiation of thirst, and the fact that oral
cooling is thirst-quenching.
PMID- 27487212
TI - Global profiling of SRP interaction with nascent polypeptides.
AB - Signal recognition particle (SRP) is a universally conserved protein-RNA complex
that mediates co-translational protein translocation and membrane insertion by
targeting translating ribosomes to membrane translocons. The existence of
parallel co- and post-translational transport pathways, however, raises the
question of the cellular substrate pool of SRP and the molecular basis of
substrate selection. Here we determine the binding sites of bacterial SRP within
the nascent proteome of Escherichia coli at amino acid resolution, by sequencing
messenger RNA footprints of ribosome-nascent-chain complexes associated with SRP.
SRP, on the basis of its strong preference for hydrophobic transmembrane domains
(TMDs), constitutes a compartment-specific targeting factor for nascent inner
membrane proteins (IMPs) that efficiently excludes signal-sequence-containing
precursors of periplasmic and outer membrane proteins. SRP associates with
hydrophobic TMDs enriched in consecutive stretches of hydrophobic and bulky
aromatic amino acids immediately on their emergence from the ribosomal exit
tunnel. By contrast with current models, N-terminal TMDs are frequently skipped
and TMDs internal to the polypeptide sequence are selectively recognized.
Furthermore, SRP binds several TMDs in many multi-spanning membrane proteins,
suggesting cycles of SRP-mediated membrane targeting. SRP-mediated targeting is
not accompanied by a transient slowdown of translation and is not influenced by
the ribosome-associated chaperone trigger factor (TF), which has a distinct
substrate pool and acts at different stages during translation. Overall, our
proteome-wide data set of SRP-binding sites reveals the underlying principles of
pathway decisions for nascent chains in bacteria, with SRP acting as the dominant
triaging factor, sufficient to separate IMPs from substrates of the SecA-SecB
post-translational translocation and TF-assisted cytosolic protein folding
pathways.
PMID- 27487213
TI - Cotranslational signal-independent SRP preloading during membrane targeting.
AB - Ribosome-associated factors must properly decode the limited information
available in nascent polypeptides to direct them to their correct cellular fate.
It is unclear how the low complexity information exposed by the nascent chain
suffices for accurate recognition by the many factors competing for the limited
surface near the ribosomal exit site. Questions remain even for the well-studied
cotranslational targeting cycle to the endoplasmic reticulum, involving
recognition of linear hydrophobic signal sequences or transmembrane domains by
the signal recognition particle (SRP). Notably, the SRP has low abundance
relative to the large number of ribosome-nascent-chain complexes (RNCs), yet it
accurately selects those destined for the endoplasmic reticulum. Despite their
overlapping specificities, the SRP and the cotranslationally acting Hsp70 display
precise mutually exclusive selectivity in vivo for their cognate RNCs. To
understand cotranslational nascent chain recognition in vivo, here we investigate
the cotranslational membrane-targeting cycle using ribosome profiling in yeast
cells coupled with biochemical fractionation of ribosome populations. We show
that the SRP preferentially binds secretory RNCs before their targeting signals
are translated. Non-coding mRNA elements can promote this signal-independent pre
recruitment of SRP. Our study defines the complex kinetic interaction between
elongation in the cytosol and determinants in the polypeptide and mRNA that
modulate SRP-substrate selection and membrane targeting.
PMID- 27487214
TI - Mammalian development: Mechanics drives cell differentiation.
PMID- 27487215
TI - Reconstruction of bacterial transcription-coupled repair at single-molecule
resolution.
AB - Escherichia coli Mfd translocase enables transcription-coupled repair by
displacing RNA polymerase (RNAP) stalled on a DNA lesion and then coordinating
assembly of the UvrAB(C) components at the damage site. Recent studies have shown
that after binding to and dislodging stalled RNAP, Mfd remains on the DNA in the
form of a stable, slowly translocating complex with evicted RNAP attached. Here
we find, using a series of single-molecule assays, that recruitment of UvrA and
UvrAB to Mfd-RNAP arrests the translocating complex and causes its dissolution.
Correlative single-molecule nanomanipulation and fluorescence measurements show
that dissolution of the complex leads to loss of both RNAP and Mfd. Subsequent
DNA incision by UvrC is faster than when only UvrAB(C) are available, in part
because UvrAB binds 20-200 times more strongly to Mfd-RNAP than to DNA damage.
These observations provide a quantitative framework for comparing complementary
DNA repair pathways in vivo.
PMID- 27487216
TI - Operation of a homeostatic sleep switch.
AB - Sleep disconnects animals from the external world, at considerable risks and
costs that must be offset by a vital benefit. Insight into this mysterious
benefit will come from understanding sleep homeostasis: to monitor sleep need, an
internal bookkeeper must track physiological changes that are linked to the core
function of sleep. In Drosophila, a crucial component of the machinery for sleep
homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB)
of the central complex. Artificial activation of these cells induces sleep,
whereas reductions in excitability cause insomnia. dFB neurons in sleep-deprived
flies tend to be electrically active, with high input resistances and long
membrane time constants, while neurons in rested flies tend to be electrically
silent. Correlative evidence thus supports the simple view that homeostatic sleep
control works by switching sleep-promoting neurons between active and quiescent
states. Here we demonstrate state switching by dFB neurons, identify dopamine as
a neuromodulator that operates the switch, and delineate the switching mechanism.
Arousing dopamine caused transient hyperpolarization of dFB neurons within tens
of milliseconds and lasting excitability suppression within minutes. Both effects
were transduced by Dop1R2 receptors and mediated by potassium conductances. The
switch to electrical silence involved the downregulation of voltage-gated A-type
currents carried by Shaker and Shab, and the upregulation of voltage-independent
leak currents through a two-pore-domain potassium channel that we term Sandman.
Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in
response to dopamine. dFB-restricted interference with the expression of Shaker
or Sandman decreased or increased sleep, respectively, by slowing the repetitive
discharge of dFB neurons in the ON state or blocking their entry into the OFF
state. Biophysical changes in a small population of neurons are thus linked to
the control of sleep-wake state.
PMID- 27487217
TI - Asymmetric division of contractile domains couples cell positioning and fate
specification.
AB - During pre-implantation development, the mammalian embryo self-organizes into the
blastocyst, which consists of an epithelial layer encapsulating the inner-cell
mass (ICM) giving rise to all embryonic tissues. In mice, oriented cell division,
apicobasal polarity and actomyosin contractility are thought to contribute to the
formation of the ICM. However, how these processes work together remains unclear.
Here we show that asymmetric segregation of the apical domain generates
blastomeres with different contractilities, which triggers their sorting into
inner and outer positions. Three-dimensional physical modelling of embryo
morphogenesis reveals that cells internalize only when differences in surface
contractility exceed a predictable threshold. We validate this prediction using
biophysical measurements, and successfully redirect cell sorting within the
developing blastocyst using maternal myosin (Myh9)-knockout chimaeric embryos.
Finally, we find that loss of contractility causes blastomeres to show ICM-like
markers, regardless of their position. In particular, contractility controls Yap
subcellular localization, raising the possibility that mechanosensing occurs
during blastocyst lineage specification. We conclude that contractility couples
the positioning and fate specification of blastomeres. We propose that this
ensures the robust self-organization of blastomeres into the blastocyst, which
confers remarkable regulative capacities to mammalian embryos.
PMID- 27487218
TI - Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes
metastasis.
AB - Metastasis is the leading cause of cancer-related death in humans. It is a
complex multistep process during which individual tumour cells spread primarily
through the circulatory system to colonize distant organs. Once in the
circulation, tumour cells remain vulnerable, and their metastatic potential
largely depends on a rapid and efficient way to escape from the blood stream by
passing the endothelial barrier. Evidence has been provided that tumour cell
extravasation resembles leukocyte transendothelial migration. However, it remains
unclear how tumour cells interact with endothelial cells during extravasation and
how these processes are regulated on a molecular level. Here we show that human
and murine tumour cells induce programmed necrosis (necroptosis) of endothelial
cells, which promotes tumour cell extravasation and metastasis. Treatment of mice
with the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-inhibitor
necrostatin-1 or endothelial-cell-specific deletion of RIPK3 reduced tumour-cell
induced endothelial necroptosis, tumour cell extravasation and metastasis. In
contrast, pharmacological caspase inhibition or endothelial-cell-specific loss of
caspase-8 promoted these processes. We furthermore show in vitro and in vivo that
tumour-cell-induced endothelial necroptosis leading to extravasation and
metastasis requires amyloid precursor protein expressed by tumour cells and its
receptor, death receptor 6 (DR6), on endothelial cells as the primary mediators
of these effects. Our data identify a new mechanism underlying tumour cell
extravasation and metastasis, and suggest endothelial DR6-mediated necroptotic
signalling pathways as targets for anti-metastatic therapies.
PMID- 27487219
TI - A partially differentiated interior for (1) Ceres deduced from its gravity field
and shape.
AB - Remote observations of the asteroid (1) Ceres from ground- and space-based
telescopes have provided its approximate density and shape, leading to a range of
models for the interior of Ceres, from homogeneous to fully differentiated. A
previously missing parameter that can place a strong constraint on the interior
of Ceres is its moment of inertia, which requires the measurement of its
gravitational variation together with either precession rate or a validated
assumption of hydrostatic equilibrium. However, Earth-based remote observations
cannot measure gravity variations and the magnitude of the precession rate is too
small to be detected. Here we report gravity and shape measurements of Ceres
obtained from the Dawn spacecraft, showing that it is in hydrostatic equilibrium
with its inferred normalized mean moment of inertia of 0.37. These data show that
Ceres is a partially differentiated body, with a rocky core overlaid by a
volatile-rich shell, as predicted in some studies. Furthermore, we show that the
gravity signal is strongly suppressed compared to that predicted by the
topographic variation. This indicates that Ceres is isostatically compensated,
such that topographic highs are supported by displacement of a denser interior.
In contrast to the asteroid (4) Vesta, this strong compensation points to the
presence of a lower-viscosity layer at depth, probably reflecting a thermal
rather than compositional gradient. To further investigate the interior
structure, we assume a two-layer model for the interior of Ceres with a core
density of 2,460-2,900 kilograms per cubic metre (that is, composed of CI and CM
chondrites), which yields an outer-shell thickness of 70-190 kilometres. The
density of this outer shell is 1,680-1,950 kilograms per cubic metre, indicating
a mixture of volatiles and denser materials such as silicates and salts. Although
the gravity and shape data confirm that the interior of Ceres evolved thermally,
its partially differentiated interior indicates an evolution more complex than
has been envisioned for mid-sized (less than 1,000 kilometres across) ice-rich
rocky bodies.
PMID- 27487220
TI - Enhanced electrocatalytic CO2 reduction via field-induced reagent concentration.
AB - Electrochemical reduction of carbon dioxide (CO2) to carbon monoxide (CO) is the
first step in the synthesis of more complex carbon-based fuels and feedstocks
using renewable electricity. Unfortunately, the reaction suffers from slow
kinetics owing to the low local concentration of CO2 surrounding typical CO2
reduction reaction catalysts. Alkali metal cations are known to overcome this
limitation through non-covalent interactions with adsorbed reagent species, but
the effect is restricted by the solubility of relevant salts. Large applied
electrode potentials can also enhance CO2 adsorption, but this comes at the cost
of increased hydrogen (H2) evolution. Here we report that nanostructured
electrodes produce, at low applied overpotentials, local high electric fields
that concentrate electrolyte cations, which in turn leads to a high local
concentration of CO2 close to the active CO2 reduction reaction surface.
Simulations reveal tenfold higher electric fields associated with metallic
nanometre-sized tips compared to quasi-planar electrode regions, and measurements
using gold nanoneedles confirm a field-induced reagent concentration that enables
the CO2 reduction reaction to proceed with a geometric current density for CO of
22 milliamperes per square centimetre at -0.35 volts (overpotential of 0.24
volts). This performance surpasses by an order of magnitude the performance of
the best gold nanorods, nanoparticles and oxide-derived noble metal catalysts.
Similarly designed palladium nanoneedle electrocatalysts produce formate with a
Faradaic efficiency of more than 90 per cent and an unprecedented geometric
current density for formate of 10 milliamperes per square centimetre at -0.2
volts, demonstrating the wider applicability of the field-induced reagent
concentration concept.
PMID- 27487221
TI - Corrigendum: Concerted nucleophilic aromatic substitution with 19F- and 18F.
PMID- 27487222
TI - Addendum: Non-Joulian magnetostriction.
PMID- 27487223
TI - Neuroscience: Flipping the sleep switch.
PMID- 27487224
TI - Cancer: Endothelial-cell killing promotes metastasis.
PMID- 27487225
TI - Multivalence Charge Transfer in Doped and Codoped Photocatalytic TiO2.
AB - The present work reports data for the mineralogical and chemical properties of
anatase thin films individually doped or codoped with chromium and vanadium,
fabricated by sol-gel spin coating on glass substrates and annealing at 450
degrees C for 2 h. X-ray photoelectron spectroscopy data indicated the presence
of Ti(4+), Ti(3+), Cr(3+), and possibly Cr(4+) in the Cr-doped thin films;
Ti(4+), Ti(3+), V(3+), V(4+), and possibly V(5+) in the V-doped thin films; and
Ti(4+), Ti(3+), Cr(3+), Cr(4+), V(3+), V(4+), and possibly V(5+) in the codoped
thin films. While the thermodynamically stable valences Ti(4+), Cr(3+), and V(5+)
would be expected to have formed, the presence of the nonequilibrium valences
Ti(3+), Cr(4+), V(3+), and V(4+) is considered to have resulted from intervalence
charge transfer for the Cr-doped and V-doped systems but from multivalence charge
transfer (MVCT) for the codoped system. The latter phenomenon, which is
introduced as a new conceptual term, describes the nature of the mutual exchange
of electrons during valence changes of both dopant (Cr, V) and matrix (Ti) ions
during annealing. In the present case, MVCT appears to be a transient metastable
condition that acts during annealing, but subsequent UV irradiation can alter its
effects.
PMID- 27487226
TI - Normal-Pressure Hydrocephalus, Sleep Apnea Syndrome, and Quality of Life in an
Octagenarian.
PMID- 27487228
TI - Prepregnancy Weight in Women with Type I Diabetes Mellitus: Effect on Pregnancy
Outcomes.
AB - Objective This study aims to evaluate the association between prepregnancy body
mass index (BMI) and adverse pregnancy outcomes in women with type 1 diabetes
mellitus (DM). Methods This is a secondary analysis of a cohort of 426
pregnancies in women with type 1 DM recruited before 20 weeks gestation. Women
were categorized according to prepregnancy BMI: low BMI (< 20 kg/m2), normal BMI
(20 to < 25 kg/m2), and high BMI (>= 25 kg/m2). The outcomes of interest were:
spontaneous abortion (delivery < 20 weeks gestation); preeclampsia; emergent
delivery for maternal indications (hypertension or placental abruption); and
preterm delivery (< 37 weeks gestation). Analyses included proportional hazards
and multiple logistic regression models with covariates: age, age at diagnosis of
type 1 DM, previous spontaneous abortion, microvascular disease (nephropathy or
retinopathy), and glycohemoglobin A1 concentrations. Results Low BMI was
associated with preterm delivery. High BMI was associated with emergent delivery
for maternal indications. Glycemic control as measured by glycohemoglobin A1 was
associated with increased risk of spontaneous abortion, attenuating the
association with low prepregnancy weight. Conclusion Prepregnancy BMI is a risk
factor to be considered when caring for women with type 1 DM, in particular for
preterm delivery (low BMI) and emergent delivery for maternal indications (high
BMI).
PMID- 27487230
TI - Association between Breast Milk and Bronchopulmonary Dysplasia: A Single Center
Observational Study.
AB - Introduction Bronchopulmonary dysplasia (BPD) is a frequent, long-term
complication in very low-birth-weight (VLBW) newborns. Its etiology is
multifactorial and the oxidative stress is one of its main causes. Breast milk
(BM) reduces oxidative stress and provides antioxidant protection, therefore, BM
may have a protective effect against BPD. Objectives This study aims to assess
the possible protective effects of BM on BPD. Methods This is a cohort study
including infants with a birth weight below 1,500 g and/or gestational age of
less than 32 weeks, born between January 2011 and October 2014. BPD was defined
as the need for supplementary oxygen for 28 days or more. Results The incidence
of BPD was 29.1%. The median amount of BM received by the patients in the first 6
weeks of life was significantly higher in patients without BPD (10.8 mL/kg/day)
than in those with BPD (2.3 mL/kg/day). The amount of BM received was inversely
associated with the incidence of BPD, even after multivariate analysis. The
cutoff point at which the protective effect emerged was an average amount of 7
mL/kg/day of BM during the first 42 days of life. Conclusion Feeding VLBW infants
with BM is associated with a lower risk of developing BPD.
PMID- 27487229
TI - Windows of Opportunity for Lifestyle Interventions to Prevent Gestational
Diabetes Mellitus.
AB - Gestational diabetes mellitus (GDM) is linked with several acute maternal health
risks and long-term development of type 2 diabetes, metabolic syndrome, and
cardiovascular disease. Intrauterine exposure to GDM similarly increases
offspring risk of early-life health complications and later disease. GDM
recurrence is common, affecting 40 to 73% of women, and augments associated
maternal/fetal/child health risks. Modifiable and independent risk factors for
GDM include maternal excessive gestational weight gain and prepregnancy
overweight and obesity. Lifestyle interventions that target diet, activity, and
behavioral strategies can effectively modify body weight. Randomized clinical
trials testing the effects of lifestyle interventions during pregnancy to reduce
excessive gestational weight gain have generally shown mixed effects on reducing
GDM incidence. Trials testing the effects of postpartum lifestyle interventions
among women with a history of GDM have shown reduced incidence of diabetes and
improved cardiovascular disease risk factors. However, the long-term effects of
interpregnancy or prepregnancy lifestyle interventions on subsequent GDM remain
unknown. Future adequately powered and well-controlled clinical trials are needed
to determine the effects of lifestyle interventions to prevent GDM and identify
pathways to effectively reach reproductive-aged women across all levels of
society, before, during, and after pregnancy.
PMID- 27487231
TI - Relationship of Hospital Staff Coverage and Delivery Room Resuscitation Practices
to Birth Asphyxia.
AB - Objective The objective of this study was to assess utilization of specialist
coverage and checklists in perinatal settings and to examine utilization by birth
asphyxia rates. Design This is a survey study of California maternity hospitals
concerning checklist use to prepare for delivery room resuscitation and 24-hour
in-house specialist coverage (pediatrician/neonatologist, obstetrician, and
obstetric anesthesiologist) and results linked to hospital birth asphyxia rates
(preterm and low weight births were excluded). Results Of 253 maternity
hospitals, 138 responded (55%); 59 (43%) indicated checklist use, and in-house
specialist coverage ranged from 38% (pediatrician/neonatologist) to 54%
(anesthesiology). In-house coverage was more common in urban versus rural
hospitals for all specialties (p < 0.0001), but checklist use was not
significantly different (p = 0.88). Higher birth volume hospitals had more
specialist coverage (p < 0.0001), whereas checklist use did not differ (p = 0.3).
In-house obstetric coverage was associated with lower asphyxia rates (odds ratio:
0.34; 95% confidence interval [CI]: 0.20, 0.58) in a regression model accounting
for other providers. Checklist use was not associated with birth asphyxia (odds
ratio: 1.12; 95% CI: 0.75, 1.68). Conclusion Higher birth volume and urban
hospitals demonstrated greater in-house specialist coverage, but checklist use
was similar across all hospitals. Current data suggest that in-house obstetric
coverage has greater impact on asphyxia than other specialist coverage or
checklist use.
PMID- 27487233
TI - Exploring the Potential Benefits and Risks of Anticoagulation for Atrial
Fibrillation During Hospitalization for Sepsis.
PMID- 27487232
TI - Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis
B Viral Load Suppression In Vivo.
AB - NK cells are important antiviral effectors, highly enriched in the liver, with
the potential to regulate immunopathogenesis in persistent viral infections. Here
we examined whether changes in the NK pool are induced when patients with eAg
positive CHB are 'primed' with PegIFNalpha and importantly, whether these changes
are sustained or further modulated long-term after switching to nucleos(t)ides
(sequential NUC therapy), an approach currently tested in the clinic.
Longitudinal sampling of a prospectively recruited cohort of patients with
eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48
weeks of PegIFNalpha was maintained at higher than baseline levels throughout the
subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNalpha-expanded NK
cells showed further augmentation in their expression of the activating NK cell
receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating,
functional NK cells was more pronounced following sequential NUCs than in
comparison cohorts of patients treated with de novo NUCs or PegIFNalpha only.
Reduction in circulating HBsAg concentrations, a key goal in the path towards
functional cure of CHB, was only achieved in those patients with enhancement of
NK cell IFNgamma and cytotoxicity but decrease in their expression of the death
ligand TRAIL. In summary, we conclude that PegIFNalpha priming can expand a
population of functional NK cells with an altered responsiveness to subsequent
antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK
cell profile show a decline in HBsAg, providing mechanistic insights for the
further optimisation of treatment strategies to achieve sustained responses in
CHB.
PMID- 27487234
TI - Construction and Nanoscale Detection of Interfacial Charge Transfer of Elegant Z
Scheme WO3/Au/In2S3 Nanowire Arrays.
AB - Elegant Z-scheme WO3/Au/In2S3 nanowire arrays were precisely constructed through
a facile step-by-step route. Surface potential change on pristine or In2S3-Au
coated WO3 single nanowire under dark and illumination detected through a Kelvin
probe force microscopy (KPFM) technique indicates that the vectorial holes
transfer of In2S3 -> Au -> WO3 should occur upon the excitation of both WO3 and
In2S3. In such charge transfer processes, the embedded Au nanoparticles in the
heterojunction systems act as a charge mediator for electrons in the conduction
band of WO3 and holes in the valence band of In2S3. The strong charge carrier
separation ability of this structure will finally enhance the oxidation ability
of WO3 with high concertation of photogenerated holes and, further, leave the
free electrons in the In2S3 with long surviving time. Therefore, the unique Z
scheme WO3/Au/In2S3 heterostructure shows great visible-light activity toward
photocatalytic reduction of CO2 in the presence of water vapor into renewable
hydrocarbon fuel (methane: CH4).
PMID- 27487235
TI - PREVALENCE OF ANTIBODY TO AND DNA OF LAWSONIA INTRACELLULARIS IN SAMPLES FROM
WILD ANIMALS IN KOREA.
AB - We evaluated the prevalence of Lawsonia intracellularis infection in three wild
animal species in Korea; the Korean water deer ( Hydropotes inermis ), Siberian
roe deer ( Capreolus pygargus ), and raccoon dogs ( Nyctereutes procyonoides ).
We collected 136 sera and 109 fecal samples from individuals in 10 Wildlife
Rescue and Conservation Centers. Serum samples were tested for anti- L.
intracellularis antibodies using a blocking enzyme-linked immunosorbent assay
(bELISA), and fecal samples were subjected to a real-time PCR assay for L.
intracellularis . Thirty-five (25.7%) sera and 36 (33.0%) fecal samples were
positive. We found a higher proportion of positive sera (64.7%, chi2=15.439,
P<0.01) and feces (58.8%, chi2=6.126, P<0.05) in raccoon dogs (chi2=11.855,
P<0.01) than in the other species (20% positive sera and 29% positive feces in
Korean water deer; 20% positive sera and 25% positive feces in Siberian roe
deer). Our data indicate infection by L. intracellularis in Korean water deer,
Siberian roe deer, and raccoon dogs throughout the country. It is imperative to
know whether these infected animal species are natural hosts for L.
intracellularis in addition to domestic pigs ( Sus scrofa domesticus).
PMID- 27487236
TI - Safety of Denosumab Versus Zoledronic Acid in Patients with Bone Metastases: A
Meta-Analysis of Randomized Controlled Trials.
AB - INTRODUCTION: Bone metastases lead to local bone destruction and skeletal
complications. Bisphosphonates, particlulaly zoledronic acid (ZA), play a central
role in the treatment of bone metastases. Some studies have shown that denosumab
may delay and prevent SREs in metastatic bone disease more effectively than ZA;
therefore, we systematically reviewed and assessed the safety of denosumab and
ZA. METHODS: The PubMed, EMBASE, Cochrane Library, Web of Science with Conference
Proceedings, Elsevier, and China National Knowledge Infrastructure (CNKI)
databases were searched up to October 2015. 2 independent reviewers extracted
data from each eligible study using a standard protocol, and both fixed-effects
and random-effects models were used to analyze and evaluate the data extracted
from eligible articles. RESULTS: 6 randomized controlled trials enrolling 13,733
patients were included. Occurrences of adverse events were generally similar
between the denosumab and ZA groups except anemia and anorexia in patients with
bone metastases and back pain and bone pain. However, occurrences of serious
adverse events such as hypocalcaemia , renal adverse events , and new primary
malignancy were significantly different between the denosumab and ZA groups. Only
the occurrence of osteonecrosis of the jaw showed no significant difference
between the denosumab and ZA groups in patients with bone metastases. CONCLUSION:
Denosumab was safer in delaying or preventing skeletal-related events in patients
with bone metastases and prevented pain progression compared to ZA in this meta
analysis.
PMID- 27487237
TI - Identification of Differentially-Expressed Genes in Response to Mycosphaerella
fijiensis in the Resistant Musa Accession 'Calcutta-4' Using Suppression
Subtractive Hybridization.
AB - Bananas and plantains are considered an important crop around the world. Banana
production is affected by several constraints, of which Black Sigatoka Disease,
caused by the fungus Mycosphaerella fijiensis, is considered one of the most
important diseases in banana plantations. The banana accession 'Calcutta-4' has a
natural resistance to Black Sigatoka; however, the fruit is not valuable for
commercialization. Gene identification and expression studies in 'Calcutta-4'
might reveal possible gene candidates for resistant to the disease and elucidate
mechanisms for resistance. A subtracted cDNA library was generated from leaves
after 6, 9 and 12 days inoculated with M. fijiensis conidia on greenhouse banana
plants of the accession 'Calcutta-4'. Bioinformatic analysis revealed 99 good
quality sequences. Blast2go analysis revealed that 31% of the sequences could not
be categorized and, according to the Biological Process Category, 32 and 28 ESTs
are related to general metabolic and cellular processes, respectively; while 10
ESTs response to stimulus. Seven sequences were redundant and one was similar to
genes that may be involved in pathogen resistance including the putative disease
resistance protein RGA1. Genes encoding zinc finger domains were identified and
may play an important role in pathogen resistance by inducing the expression of
downstream genes. Expression analysis of four selected genes was performed using
RT-qPCR during the early stage of the disease development at 6, 9, 12 and 15 days
post inoculation showing a peak of up regulation at 9 or 12 days post
inoculation. Three of the four genes showed an up-regulation of expression in
'Calcutta-4' when compared to 'Williams' after inoculation with M. fijiensis,
suggesting a fine regulation of specific gene candidates that may lead to a
resistance response. The genes identified in early responses in a plant-pathogen
interaction may be relevant for the resistance response of 'Calcutta-4' to Black
Sigatoka. Genes with different functions may play a role in plant response to the
disease. The present study suggests a fine up regulation of these genes that
might be needed to perform an incompatible interaction. Further gene functional
studies need to be performed to validate their use as candidate resistance genes
in susceptible banana cultivars.
PMID- 27487238
TI - Remotely Sensed Data Informs Red List Evaluations and Conservation Priorities in
Southeast Asia.
AB - The IUCN Red List has assessed the global distributions of the majority of the
world's amphibians, birds and mammals. Yet these assessments lack explicit
reference to widely available, remotely-sensed data that can sensibly inform a
species' risk of extinction. Our first goal is to add additional quantitative
data to the existing standardised process that IUCN employs. Secondly, we ask: do
our results suggest species of concern-those at considerably greater risk than
hitherto appreciated? Thirdly, these assessments are not only important on a
species-by-species basis. By combining distributions of species of concern, we
map conservation priorities. We ask to what degree these areas are currently
protected and how might knowledge from remote sensing modify the priorities?
Finally, we develop a quick and simple method to identify and modify the priority
setting in a landscape where natural habitats are disappearing rapidly and so
where conventional species' assessments might be too slow to respond. Tropical,
mainland Southeast Asia is under exceptional threat, yet relatively poorly known.
Here, additional quantitative measures may be particularly helpful. This region
contains over 122, 183, and 214 endemic mammals, birds, and amphibians,
respectively, of which the IUCN considers 37, 21, and 37 threatened. When
corrected for the amount of remaining natural habitats within the known elevation
preferences of species, the average sizes of species ranges shrink to <40% of
their published ranges. Some 79 mammal, 49 bird, and 184 amphibian ranges are
<20,000km2-an area at which IUCN considers most other species to be threatened.
Moreover, these species are not better protected by the existing network of
protected areas than are species that IUCN accepts as threatened. Simply, there
appear to be considerably more species at risk than hitherto appreciated.
Furthermore, incorporating remote sensing data showing where habitat loss is
prevalent changes the locations of conservation priorities.
PMID- 27487239
TI - A passenger strand variant in miR-196a2 contributes to asthma severity in
children and adolescents: A preliminary study.
AB - There is emerging evidence to support the role of microRNAs in allergic airway
diseases and inflammation. Genetic variants in microRNA genes might affect
microRNA-mediated cell regulation. This preliminary study was designed to
investigate the association of the microRNA-196a2 rs11614913 (C/T) polymorphism
with susceptibility to asthma and clinical outcomes in children and adolescents.
Genotyping of rs11614913 polymorphism was determined in 96 patients with
bronchial asthma (6-18 years of age) and 96 unrelated controls, using real-time
polymerase chain reaction technology. In-silico target prediction and network
core analyses were performed. The asthmatics did not show significant differences
in genotype distribution (p = 0.609) and allele frequencies (p = 0.428) compared
with the controls. There were also no associations with disease duration, age at
onset, asthma phenotype, asthma control, therapeutic level, airway hyper
responsiveness, or biochemical parameters in the blood. However, the CC genotype
was associated with a more severe degree of asthma (p = 0. 023) and higher
frequency of nocturnal asthma (p = 0.002). Carriers for CC were 17 times more
likely to develop nocturnal asthma, and had a more than 2.5-fold increased risk
for poor disease outcome compared with CT and TT individuals. In conclusion,
microRNA-196a2 rs11614913 polymorphism might be associated with asthma severity
in our sample of the Egyptian population. Further investigations in studies with
a larger sample size and functional tests are needed to validate our findings and
to explore the detailed biological mechanisms.
PMID- 27487240
TI - MR Image Analytics to Characterize the Upper Airway Structure in Obese Children
with Obstructive Sleep Apnea Syndrome.
AB - PURPOSE: Quantitative image analysis in previous research in obstructive sleep
apnea syndrome (OSAS) has focused on the upper airway or several objects in its
immediate vicinity and measures of object size. In this paper, we take a more
general approach of considering all major objects in the upper airway region and
measures pertaining to their individual morphological properties, their tissue
characteristics revealed by image intensities, and the 3D architecture of the
object assembly. We propose a novel methodology to select a small set of salient
features from this large collection of measures and demonstrate the ability of
these features to discriminate with very high prediction accuracy between obese
OSAS and obese non-OSAS groups. MATERIALS AND METHODS: Thirty children were
involved in this study with 15 in the obese OSAS group with an apnea-hypopnea
index (AHI) = 14.4 +/- 10.7) and 15 in the obese non-OSAS group with an AHI = 1.0
+/- 1.0 (p<0.001). Subjects were between 8-17 years and underwent T1- and T2
weighted magnetic resonance imaging (MRI) of the upper airway during wakefulness.
Fourteen objects in the vicinity of the upper airways were segmented in these
images and a total of 159 measurements were derived from each subject image which
included object size, surface area, volume, sphericity, standardized T2-weighted
image intensity value, and inter-object distances. A small set of discriminating
features was identified from this set in several steps. First, a subset of
measures that have a low level of correlation among the measures was determined.
A heat map visualization technique that allows grouping of parameters based on
correlations among them was used for this purpose. Then, through T-tests, another
subset of measures which are capable of separating the two groups was identified.
The intersection of these subsets yielded the final feature set. The accuracy of
these features to perform classification of unseen images into the two patient
groups was tested by using logistic regression and multi-fold cross validation.
RESULTS: A set of 16 features identified with low inter-feature correlation (<
0.36) yielded a high classification accuracy of 96% with sensitivity and
specificity of 97.8% and 94.4%, respectively. In addition to the previously
observed increase in linear size, surface area, and volume of adenoid, tonsils,
and fat pad in OSAS, the following new markers have been found. Standardized T2
weighted image intensities differed between the two groups for the entire neck
body region, pharynx, and nasopharynx, possibly indicating changes in object
tissue characteristics. Fat pad and oropharynx become less round or more complex
in shape in OSAS. Fat pad and tongue move closer in OSAS, and so also oropharynx
and tonsils and fat pad and tonsils. In contrast, fat pad and oropharynx move
farther apart from the skin object. CONCLUSIONS: The study has found several new
anatomic bio-markers of OSAS. Changes in standardized T2-weighted image
intensities in objects may imply that intrinsic tissue composition undergoes
changes in OSAS. The results on inter-object distances imply that treatment
methods should respect the relationships that exist among objects and not just
their size. The proposed method of analysis may lead to an improved understanding
of the mechanisms underlying OSAS.
PMID- 27487241
TI - Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: A Single-Institution
Experience and a Review of the Literature.
AB - OBJECTIVES: The aim of this study was to evaluate the role of neoadjuvant
chemotherapy (NACT) in advanced ovarian carcinoma patients unable to undergo a
complete resection during primary debulking surgery. METHODS: From February 2005
to October 2015, all consecutive cases of advanced-stage epithelial ovarian
carcinoma at the University of Bari were retrospectively recorded. Of them,
patients treated with NACT were collected. Kaplan-Meier and Cox proportional
hazards analyses were used to determine the predictors of survival. RESULTS:
Seventy-eight women with advanced-stage epithelial ovarian carcinoma were treated
with NACT. On univariate analysis, age (p = 0.003), CA-125 serum level (0.001),
response to NACT (p < 0.0001), stage of disease (p = 0.011) and optimal debulking
surgery (p < 0.0001) were found to be important prognostic factors related to
survival. However, on multivariate analysis, age, response to NACT, CA-125 serum
level and optimal debulking surgery remained as independent poor prognostic
factors for survival. The median overall and disease-free survival were 31 and 12
months, respectively. CONCLUSIONS: NACT does not compromise survival in patients
with stage IIIC and IV ovarian cancer compared to patients treated with primary
surgery. Prospective randomized trials comparing NACT to conventional treatment
are needed to determine the quality of life and cost/benefit outcomes for women
presenting advanced epithelial ovarian cancer.
PMID- 27487242
TI - Research on B Cell Algorithm for Learning to Rank Method Based on Parallel
Strategy.
AB - For the purposes of information retrieval, users must find highly relevant
documents from within a system (and often a quite large one comprised of many
individual documents) based on input query. Ranking the documents according to
their relevance within the system to meet user needs is a challenging endeavor,
and a hot research topic-there already exist several rank-learning methods based
on machine learning techniques which can generate ranking functions
automatically. This paper proposes a parallel B cell algorithm, RankBCA, for rank
learning which utilizes a clonal selection mechanism based on biological
immunity. The novel algorithm is compared with traditional rank-learning
algorithms through experimentation and shown to outperform the others in respect
to accuracy, learning time, and convergence rate; taken together, the
experimental results show that the proposed algorithm indeed effectively and
rapidly identifies optimal ranking functions.
PMID- 27487243
TI - Locating and Activating Molecular 'Time Bombs': Induction of Mycolata Prophages.
AB - Little is known about the prevalence, functionality and ecological roles of
temperate phages for members of the mycolic acid producing bacteria, the
Mycolata. While many lytic phages infective for these organisms have been
isolated, and assessed for their suitability for use as biological control agents
of activated sludge foaming, no studies have investigated how temperate phages
might be induced for this purpose. Bioinformatic analysis using the PHAge Search
Tool (PHAST) on Mycolata whole genome sequence data in GenBank for members of the
genera Gordonia, Mycobacterium, Nocardia, Rhodococcus, and Tsukamurella revealed
83% contained putative prophage DNA sequences. Subsequent prophage inductions
using mitomycin C were conducted on 17 Mycolata strains. This led to the
isolation and genome characterization of three novel Caudovirales temperate
phages, namely GAL1, GMA1, and TPA4, induced from Gordonia alkanivorans, Gordonia
malaquae, and Tsukamurella paurometabola, respectively. All possessed highly
distinctive dsDNA genome sequences.
PMID- 27487244
TI - Tableting Properties and Compression Models of Labisia pumila Tablets.
AB - The tableting properties of Labisia pumila herbal powder, which is well known for
its therapeutic benefits was investigated. The herbal powder was compressed into
tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with
compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g
were used to form tablets. Some empirical models were used to describe the
compressibility behavior of Labisia pumila tablets. The strength and density of
tablets increased with increase in compaction pressure and resulted in reduction
in porosity of the tablets. Smaller feeds, higher forces and increase in
compaction pressure, contributed to more coherent tablets. These findings can be
used to enhance the approach and understanding of tableting properties of Labisia
pumila herbal powder tablets.
PMID- 27487246
TI - Photochemical Deposition of Silver Nanoparticles on Clays and Exploring Their
Antibacterial Activity.
AB - Photochemical method was used to synthesize silver nanoparticles (AgNPs) in the
presence of citrate or clay (SWy-1, SYn-1, and Laponite B) as stabilizers and
Lucirin TPO as photoinitiator. During the photochemical synthesis, an appearance
of the plasmon absorption band was seen around 400 nm, indicating the formation
of AgNPs. X-ray diffraction results suggested that AgNPs prepared in SWy-1 were
adsorbed into interlamellar space, and moreover, showed some clay exfoliation. In
the case of SYn-1, AgNPs was not intercalated. For the AgNP/Lap B sample, the
formation of an exfoliated structure occurred. Transmission electron microscopy
revealed the spherical shape of AgNPs for all samples. The particle sizes
obtained for AgNP/SWy-1, AgNP/SYn-1, and AgNP/Lap B were 2.6, 5.1, and 3.8 nm,
respectively. AgNPs adsorbed on SYn-1 reveal nonuniform size and aggregation of
some particles. However, AgNP/SWy-1 and AgNP/Lap B samples are more uniform and
have diameters smaller than those prepared with SYn-1. This behavior is due to
the ability to exfoliate these clays. The antibacterial activities of pure clays,
AgNP/citrate, and AgNP/clays were investigated against Escherichia coli (E. coli)
and Staphylococcus aureus (S. aureus). AgNPs in the presence of clays (AgNPs/SYn
1 and AgNPs/SWy-1) showed a lower survival index percentage compared to those
obtained for pure clays and AgNPs. The AgNP/SWy-1 sample showed good
antibacterial activity against both tested species and the lowest survival index
of 3.9 and 4.3 against E. coli and S. aureus, respectively. AgNPs are located in
the interlayer region of the SWy-1, which has acid sites. These acidic sites may
contribute to the release of Ag(+) ions from the surface of AgNPs. On the other
hand, Laponite B and AgNP/Lap B samples did not demonstrate any bactericidal
activity.
PMID- 27487247
TI - Variability of nitrifying communities in surface coastal waters of the Eastern
South Pacific (~36 degrees S).
AB - We report the seasonal and single-diurnal variability of potentially active
members of the prokaryote community in coastal surface waters off central Chile
and the relationship between nitrifiers and solar radiation by combining 16S cDNA
based pyrosequencing, RT-qPCR of specific gene markers for nitrifiers (amoA, for
general AOA, AOA-A, AOA-B, Nitrosopumilus maritimus and beta-AOB; and 16S rRNA
gene for Nitrospina-like NOB), and solar irradiance measurements. We also
evaluated the effects of artificial UVA-PAR and PAR spectra on nitrifiers by RT
qPCR. All nitrifiers (except AOA-B ecotype) were detected via RT-qPCR but AOA was
the only group detected by pyrosequencing. Results showed high variability in
their transcriptional levels during the day which could be associated to sunlight
intensity thresholds in winter although AOA and Nitrospina-like NOB transcript
number were also potentially related with environmental substrate availability.
Only N. maritimus amoA transcripts showed a significant negative correlation with
solar irradiances in both periods. During spring-summer, Nitrospina transcripts
decreased at higher sunlight intensities, whereas the opposite was found during
winter under natural (in situ) and artificial light experiments. In summary, a
nitrifying community with variable tolerance to solar radiation is responsible
for daily nitrification, and was particularly diverse during winter in the study
area.
PMID- 27487245
TI - CLIMP: Clustering Motifs via Maximal Cliques with Parallel Computing Design.
AB - A set of conserved binding sites recognized by a transcription factor is called a
motif, which can be found by many applications of comparative genomics for
identifying over-represented segments. Moreover, when numerous putative motifs
are predicted from a collection of genome-wide data, their similarity data can be
represented as a large graph, where these motifs are connected to one another.
However, an efficient clustering algorithm is desired for clustering the motifs
that belong to the same groups and separating the motifs that belong to different
groups, or even deleting an amount of spurious ones. In this work, a new motif
clustering algorithm, CLIMP, is proposed by using maximal cliques and sped up by
parallelizing its program. When a synthetic motif dataset from the database
JASPAR, a set of putative motifs from a phylogenetic foot-printing dataset, and a
set of putative motifs from a ChIP dataset are used to compare the performances
of CLIMP and two other high-performance algorithms, the results demonstrate that
CLIMP mostly outperforms the two algorithms on the three datasets for motif
clustering, so that it can be a useful complement of the clustering procedures in
some genome-wide motif prediction pipelines. CLIMP is available at
http://sqzhang.cn/climp.html.
PMID- 27487248
TI - Maternal PTSD and Children's Adjustment: Parenting Stress and Emotional
Availability as Proposed Mediators.
AB - OBJECTIVES: Maternal posttraumatic stress disorder (PTSD) is a risk factor for
negative child adjustment, but it is unclear whether this association is direct
(e.g., a mother's PTSD symptoms are observed, learned, and internalized by
children which results in behavioral and emotional problems) or indirect, through
parent-child relationship difficulties or parenting stress. We hypothesized that
parenting stress and maternal emotional availability would exhibit indirect
effects on relationships between maternal PTSD and children's functioning.
METHOD: Participants were 52 trauma-exposed mothers and their children (aged 7-12
years). Mothers completed measures of PTSD and parenting stress and reported on
their children's functioning. Emotional availability was assessed through
observer-rated mother-child interactions. RESULTS: Emotional availability was not
related to PTSD or child outcomes. Parenting stress had a substantial indirect
effect on the relationships between maternal PTSD and child emotion regulation,
internalizing, and externalizing behaviors. CONCLUSIONS: Results highlight the
need to target parenting stress in interventions with trauma-exposed families.
PMID- 27487249
TI - The use of micro-electro mechanical systems in vascular monitoring: implications
for clinical use.
AB - INTRODUCTION: BioMEMS relates to the implementation of Micro-Electro-Mechanical
Systems (MEMS), in the biological and medical sphere. BioMEMS sensors are being
utilized for many clinical applications, including a wireless urinary pressure
system, right heart pressure sensor, and measurements on shearing force on the
vascular system An important application of BioMEMS is on Heart failure (HF), a
common disease, with a prevalence of 10% or more in persons 70 years of age or
older, associated with high morbidity and mortality. HF affects over 5 million
people and contributes to over 200,000 deaths a year in the United States alone.
AREAS COVERED: The purpose of this paper is to provide a short overview on the
successful implementation of BioMEMS sensors in heart failure and vascular
medicine. Expert commentary: BioMEMS devices have overcome current limitations in
pharmacotherapies for resistant hypertension by electrical modulation of the
baroreceeptors. This represents a step towards the development of biomedical
micro-devices for those conditions in which pharmacotherapies result poorly
effective or elicit unacceptable toxicity.
PMID- 27487251
TI - Optimization of a Digital Medicine System in Psychiatry.
AB - BACKGROUND: Nonadherence to medication compromises the effectiveness of
psychiatric treatments in patients with serious mental illness (SMI). A newly
developed digital medicine system (DMS) offers an opportunity to objectively
assess and report patient medication adherence. DMS includes a wearable sensor
that receives a data signal from a medication tablet with an embedded ingestible
sensor after ingestion of the medication and transmits that data to the patient's
mobile device to display health care information for the patient and treatment
team. METHODS/RESULTS: Development of a DMS requires a program that investigates
safety, tolerability, and usability of the system in patients with SMI. It
necessitates rapid design adaptation of the individual components and the
integrated system and human factors studies with the intended users. This article
describes the program's methodology and shows results from 3 early studies,
conducted in 2013 and 2014, to illustrate diversity of the programs' methodology.
First, a standard 28-day study showed minimal skin irritation and demonstrated
acceptable wearability of the wearable sensor. Second, a 16-week study provided
usability feedback from patients with SMI and caregivers to improve the mobile
application. Third, end-to-end bench-level integrated system testing led to
multiple substudies of a master protocol (ClinicalTrials.gov identifier:
NCT02091882) to investigate various aspects of the system (eg, ingestible sensor
detection and latency). CONCLUSIONS: To develop a DMS in psychiatry, the system's
multiple components must be considered simultaneously using various
methodologies. A focus on usability, along with agile evaluation and feedback
across studies, provides an optimal strategy for ensuring patient acceptance and
successful regulatory review.
PMID- 27487253
TI - Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma
and Surgical Patients: A Randomized Clinical Trial.
AB - Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism
(VTE) in surgical and trauma patients. However, VTE remains an important source
of morbidity and mortality, potentially exacerbated by antithrombin III or anti
Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a
difference in reaction time (time to initial fibrin formation) greater than 1
minute between heparinase and standard thrombelastogram (TEG) is associated with
a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted
prophylactic enoxaparin dosing among trauma and surgical patients. Design,
Setting, and Participants: This randomized clinical trial, conducted from October
2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted
enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients
screened for VTE at 3 level I trauma centers in the United States. Main Outcomes
and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa
deficiency, and antithrombin III deficiency. Results: Of the 185 trial
participants, 89 were randomized to the control group (median age, 44.0 years;
55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0%
male). Patients in the intervention group received a higher median enoxaparin
dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa
levels in intervention patients were not higher than levels in control patients
until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved
a difference in reaction time greater than 1 minute, which was similar between
the control and intervention groups (10.4% vs 13.5%; P = .68). The time to
enoxaparin initiation was similar between the control and intervention groups
(median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of
patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P
= .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the
difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not
statistically significant. Antithrombin III and anti-Factor Xa deficiencies and
hypercoagulable TEG parameters, including elevated coagulation index (>3),
maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both
groups. Identified risk factors for VTE included older age (61.0 years vs 46.0
years; P = .04), higher body mass index (calculated as weight in kilograms
divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute
Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and
increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05).
Conclusions and Relevance: The incidence of VTE was low and similar between
groups; however, few patients achieved a difference in reaction time greater than
1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were
prevalent among patients with VTE. Low VTE incidence may be due to an early time
to enoxaparin initiation and an overall healthier and less severely injured study
population than previously reported. Trial Registration: clinicaltrials.gov
Identifier: NCT00990236.
PMID- 27487250
TI - Metabolite transport and associated sugar signalling systems underpinning
source/sink interactions.
AB - Metabolite transport between organelles, cells and source and sink tissues not
only enables pathway co-ordination but it also facilitates whole plant
communication, particularly in the transmission of information concerning
resource availability. Carbon assimilation is co-ordinated with nitrogen
assimilation to ensure that the building blocks of biomass production, amino
acids and carbon skeletons, are available at the required amounts and
stoichiometry, with associated transport processes making certain that these
essential resources are transported from their sites of synthesis to those of
utilisation. Of the many possible posttranslational mechanisms that might
participate in efficient co-ordination of metabolism and transport only
reversible thiol-disulphide exchange mechanisms have been described in detail.
Sucrose and trehalose metabolism are intertwined in the signalling hub that
ensures appropriate resource allocation to drive growth and development under
optimal and stress conditions, with trehalose-6-phosphate acting as an important
signal for sucrose availability. The formidable suite of plant metabolite
transporters provides enormous flexibility and adaptability in inter-pathway
coordination and source-sink interactions. Focussing on the carbon metabolism
network, we highlight the functions of different transporter families, and the
important of thioredoxins in the metabolic dialogue between source and sink
tissues. In addition, we address how these systems can be tailored for crop
improvement.
PMID- 27487254
TI - Supercharging Reagent for Enhanced Liquid Chromatographic Separation and Charging
of Sialylated and High-Molecular-Weight Glycopeptides for NanoHPLC-ESI-MS/MS
Analysis.
AB - Recent developments in proteomic techniques have led to the development of mass
spectrometry (MS)-based methods to characterize site-specific glycosylation of
proteins. However, appropriate analytical tools to characterize acidic and high
molecular-weight (hMW) glycopeptides are still lacking. In this study, we
demonstrate that the addition of supercharging reagent, m-nitrobenzyl alcohol (m
NBA), into mobile phases greatly facilitates the analysis of acidic and hMW
glycopeptides. Using commercial glycoproteins, we demonstrated that in the
presence of m-NBA the charge state of sialylated glycopeptides increased and the
chromatographic separation of neutral and acidic glycopeptides revealed a
remarkable improvement. Next, we applied this system to the characterization of a
glycoconjugate vaccine candidate consisting of a genetically detoxified exotoxin
A of Pseudomonas aeruginosa covalently linked to Shigella flexneri type 2a O
antigen (Sf2E) produced by engineered Escherichia coli. The addition of m-NBA,
allowed us to identify peptides with glycan chains of unprecedented size, up to
20 repeat units (98 monosaccharides). Our results indicated that incorporation of
m-NBA into reversed-phase liquid chromatography (LC) solvents improves
sensitivity, charging, and chromatographic resolution for acidic and hMW
glycopeptides.
PMID- 27487252
TI - Azoreductases in drug metabolism.
AB - : Azoreductases are flavoenzymes that have been characterized in a range of
prokaryotes and eukaryotes. Bacterial azoreductases are associated with the
activation of two classes of drug, azo drugs for the treatment of inflammatory
bowel disease and nitrofuran antibiotics. The mechanism of reduction of azo
compounds is presented; it requires tautomerisation of the azo compound to a
quinoneimine and provides a unifying mechanism for the reduction of azo and
quinone substrates by azoreductases. The importance of further work in the
characterization of azoreductases from enteric bacteria is highlighted to aid in
the development of novel drugs for the treatment of colon related disorders.
Human azoreductases are known to play a crucial role in the metabolism of a
number of quinone-containing cancer chemotherapeutic drugs. The mechanism of
hydride transfer to quinones, which is shared not only between eukaryotic and
prokaryotic azoreductases but also the wider family of NAD(P)H quinone
oxidoreductases, is outlined. The importance of common single nucleotide
polymorphisms (SNPs) in human azoreductases is described not only in cancer
prognosis but also with regard to their effects on the efficacy of quinone drug
based cancer chemotherapeutic regimens. This highlights the need to screen
patients for azoreductase SNPs ahead of treatment with these regimens. LINKED
ARTICLES: This article is part of a themed section on Drug Metabolism and
Antibiotic Resistance in Micro-organisms. To view the other articles in this
section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.
PMID- 27487255
TI - Investigating nurse practitioners in the private sector: a theoretically informed
research protocol.
AB - AIMS AND OBJECTIVES: To report a study protocol and the theoretical framework
normalisation process theory that informs this protocol for a case study
investigation of private sector nurse practitioners. BACKGROUND: Most research
evaluating nurse practitioner service is focused on public, mainly acute care
environments where nurse practitioner service is well established with strong
structures for governance and sustainability. Conversely, there is lack of
clarity in governance for emerging models in the private sector. In a climate of
healthcare reform, nurse practitioner service is extending beyond the familiar
public health sector. Further research is required to inform knowledge of the
practice, operational framework and governance of new nurse practitioner models.
DESIGN: The proposed research will use a multiple exploratory case study design
to examine private sector nurse practitioner service. METHODS: Data collection
includes interviews, surveys and audits. A sequential mixed method approach to
analysis of each case will be conducted. Findings from within-case analysis will
lead to a meta-synthesis across all four cases to gain a holistic understanding
of the cases under study, private sector nurse practitioner service.
Normalisation process theory will be used to guide the research process,
specifically coding and analysis of data using theory constructs and the relevant
components associated with those constructs. CONCLUSIONS: This article provides a
blueprint for the research and describes a theoretical framework, normalisation
process theory in terms of its flexibility as an analytical framework. RELEVANCE
TO CLINICAL PRACTICE: Consistent with the goals of best research practice, this
study protocol will inform the research community in the field of primary health
care about emerging research in this field. Publishing a study protocol ensures
researcher fidelity to the analysis plan and supports research collaboration
across teams.
PMID- 27487256
TI - Tyrosine-Coordinated P-Cluster in G. diazotrophicus Nitrogenase: Evidence for the
Importance of O-Based Ligands in Conformationally Gated Electron Transfer.
AB - The P-cluster is a unique iron-sulfur center that likely functions as a dynamic
electron (e(-)) relay site between the Fe-protein and the catalytic FeMo-cofactor
in nitrogenase. The P-cluster has been shown to undergo large conformational
changes upon 2-e(-) oxidation which entail the coordination of two of the Fe
centers to a Ser side chain and a backbone amide N, respectively. Yet, how and if
this 2-e(-) oxidized state (P(OX)) is involved in catalysis by nitrogenase is not
well established. Here, we present the crystal structures of reduced and oxidized
MoFe-protein (MoFeP) from Gluconacetobacter diazotrophicus (Gd), which natively
possesses an Ala residue in the position of the Ser ligand to the P-cluster.
While reduced Gd-MoFeP is structurally identical to previously characterized
counterparts around the FeMo-cofactor, oxidized Gd-MoFeP features an unusual Tyr
coordination to its P-cluster along with ligation by a backbone amide nitrogen.
EPR analysis of the oxidized Gd-MoFeP P-cluster confirmed that it is a 2-e(-)
oxidized, integer-spin species. Importantly, we have found that the sequence
positions corresponding to the Ser and Tyr ligands are almost completely
covariant among Group I nitrogenases. These findings strongly support the
possibility that the P(OX) state is functionally relevant in nitrogenase
catalysis and that a hard, O-based anionic ligand serves to stabilize this state
in a switchable fashion.
PMID- 27487257
TI - The genetic architecture of freezing tolerance varies across the range of
Arabidopsis thaliana.
AB - The capacity to tolerate freezing temperatures limits the geographical
distribution of many plants, including several species of agricultural
importance. However, the genes involved in freezing tolerance remain largely
unknown. Here, we describe the variation in constitutive freezing tolerance that
occurs among worldwide accessions of Arabidopsis thaliana. We found that although
plants from high latitudes tend to be more freezing tolerant than plants from low
latitudes, the environmental factors that shape cold adaptation differ across the
species range. Consistent with this, we found that the genetic architecture of
freezing tolerance also differs across its range. Conventional genome-wide
association studies helped identify a priori and other promising candidate genes.
However, simultaneously modelling climate variables and freezing tolerance
together pinpointed other excellent a priori candidate genes. This suggests that
if the selective factor underlying phenotypic variation is known, multi-trait
mixed models may aid in identifying the genes that underlie adaptation.
PMID- 27487258
TI - Understanding Substance Use and Addiction Through the Lyrics of Black Sabbath: A
Content Analysis.
AB - BACKGROUND: Heavy metal music is distinguished for its deep sound and lyrical
fixation with dark themes including war, destruction, doom, and misery. Such
subjects permeate the music of Black Sabbath, the band generally considered the
pioneers of heavy metal. One theme-substance use-is recurrent in Black Sabbath's
songs and personal lives of its members. OBJECTIVE/METHODS: This study explored
the band's relationship with substance use though a content analysis of all songs
containing lyrics written and recorded in studio by Black Sabbath. The analysis
included 156 songs across 19 albums recorded from 1970 to 2013. RESULTS: Three
key findings emerged. First, a minority of songs (13%) contained substance
references. Second, the songs with substance references were overwhelmingly (60%)
negative, a pattern that increased over time. Third, despite many line-up changes
over the band's 43-year period, every song referencing substance use except one
featured vocalist Ozzy Osbourne and lyricist Geezer Butler. CONCLUSION: Contrary
to the notion that heavy metal music glorifies or encourages substance use
(Record Labeling, United States Senate, 1985), Black Sabbath's lyrics as a whole
weave a cautionary tale of how persistent substance use can hijack free will,
become the dominant focus of the affected individual, and produce myriad forms of
human misery. The insidiousness of chronic substance use depicted by the lyrics
mirrors findings from natural-history studies of individuals with substance use
disorders and aligns with neurobiological heuristics of addiction.
PMID- 27487260
TI - Measuring citalopram in blood and central nervous system: revealing a
distribution pattern that differs from other antidepressants: Erratum.
PMID- 27487259
TI - Effects of switching to aripiprazole from current atypical antipsychotics on
subsyndromal symptoms and tolerability in patients with bipolar disorder.
AB - We evaluated the effectiveness of aripiprazole among bipolar patients who had
switched to this medication as a result of difficulty maintaining on their
prestudy atypical antipsychotics (AAPs) because of subsyndromal mood symptoms or
intolerance. This study included 77 bipolar patients who were in syndromal
remission with an AAP as monotherapy or with an AAP combined with a mood
stabilizer(s) who needed to switch from their present AAP because of subsyndromal
symptoms or intolerance. At 24 weeks after switching to aripiprazole, the
remission rates on the Montgomery-Asberg Depression Rating Scale (MADRS) and on
both the MADRS and the Young Mania Rating Scale were increased significantly in
the full sample and in the inefficacy subgroup. In the inefficacy subgroup, the
MADRS score change was significant during the 24 weeks of study. Total
cholesterol and prolactin decreased significantly after switching to
aripiprazole. The proportion of patients who had abnormal values for central
obesity and hypercholesterolemia decreased significantly from baseline to week
24. These findings suggest that a change from the current AAP to aripiprazole was
associated with improvement in subsyndromal mood symptoms and several
lipid/metabolic or safety profile parameters in patients with bipolar disorder
with tolerability concerns or subsyndromal mood symptoms.
PMID- 27487261
TI - Development, optimization and in vitro evaluation of norcantharidin loadedself
nanoemulsifying drug delivery systems (NCTD-SNEDDS).
AB - This study focused on developing a self-nanoemulsifying drug delivery system
(SNEDDS) containing bioactive surfactants under an efficient screening approach
for overcoming problems associated with the delivery of norcantharidin (NCTD), a
high dose chemotherapy agent having pH dependent solubility. Preliminary
screening was implemented to select proper components combination. Besides the
solubility of NCTD in the oil phase, emulsifying efficiency, droplet size and
size distribution were also employed to select components of the SNEDDS.
Moreover, the influence of surfactant and co-surfactant on the interfacial
tension and droplets of nanoemulsions were investigated to further understand the
mechanism of spontaneous emulsification. Co-surfactant addition promoted the
emulsification via reducing the water/oil interfacial tension and viscosity.
Ternary phase diagrams were constructed to investigate the phase behavior and
designate the optimum systems. The alternative formulations were characterized
for cloud point, dilution robustness, droplet size, polydispersity index (PDI)
and transmission electron microscopy (TEM). In vitro dissolution study showed
that the dissolution rate of optimized formulation (NCTD 10 mg/g, EO 50 wt.%,
Cremophor EL 35 wt.%, ethylene glycol 15 wt.%) was slower than drug suspension
under the same conditions, confirming that the developed SNEDDS formulation would
exhibit sustained release potential.
PMID- 27487262
TI - The Relationship between Obesity, Prostate Tumor Infiltrating Lymphocytes and
Macrophages, and Biochemical Failure.
AB - BACKGROUND: Obesity reflects a chronic inflammatory environment that may
contribute to prostate cancer progression and poor treatment outcomes. However,
it is not clear which mechanisms drive this association within the tumor
microenvironment. The aim of this pilot study was to examine prostatic
inflammation via tumor infiltrating lymphocytes and macrophages characterized by
obesity and cancer severity. METHODS: We studied paraffin-embedded prostatectomy
tissue from 99 participants (63 non-obese and 36 obese) from the Study of
Clinical Outcomes, Risk and Ethnicity (University of Pennsylvania). Pathologists
analyzed the tissue for type and count of lymphocytes and macrophages, including
CD3, CD8, FOXP3, and CD68. Pathology data were linked to clinical and demographic
variables. Statistical analyses included frequency tables, Kruskal-Wallis tests,
Spearman correlations, and multivariable models. RESULTS: We observed positive
univariate associations between the number of CD68 cells and tumor grade (p =
0.019). In multivariable analysis, CD8 counts were associated with time to
biochemical failure (HR = 1.09, 95% CI = 1.004-1.192, p-value = 0.041.) There
were no differences in lymphocytes or macrophages by obesity status or BMI.
CONCLUSIONS: The number of lymphocytes and macrophages in the tumor
microenvironment did not differ by obesity status. However, these inflammation
markers were associated with poor prostate cancer outcomes. Further examination
of underlying mechanisms that influence obesity-related effects on prostate
cancer outcomes is warranted. Such research will guide immunotherapy protocols
and weight management as they apply to diverse patient populations and
phenotypes.
PMID- 27487263
TI - Association Between Depression and Hospital Admission in Older Men with Prostate
Cancer.
PMID- 27487264
TI - Preparation of benznidazole pellets for immediate drug delivery using the
extrusion spheronization technique.
AB - Recent advances in the treatment of Chagas disease have followed combinations of
drugs that act synergistically against infection, predominantly including
benznidazole (BNZ) and azoles derivatives. Possible incompatibilities between
these drugs, slow dissolution of BNZ and dose adjustment difficulties are
technological obstacles to the development of multidrug formulations. Thus, in
the present study, BNZ pellets were developed using extrusion spheronization for
immediate drug delivery. Preformulation studies were then performed using thermal
analysis and infrared spectroscopy and compatibility between the drug and
selected excipients (polyethylene glycol 6000, sodium starch glycolate,
microcrystalline cellulose and sodium croscarmellose) was investigated. No
chemical decomposition of BNZ was observed, even in samples submitted to wet
granulation and thermal stress. Subsequently, formulations were elaborated
according to a simplex lattice experimental design using polyethylene glycol,
sodium starch glycolate and sodium croscarmellose as disintegrating agents. In
these experiments, BNZ pellets showed appropriate physicochemical
characteristics, including high drug load capacity and excellent flow properties.
The mixture experimental design allowed identification of adequate compositions
of disintegrating agents and achieved rapid disintegration and dissolution of
pellets. Optimum performance was achieved using polyethylene glycol and sodium
croscarmellose at 5.0% w/w each. The present BNZ pellets are versatile
alternatives to treat Chagas disease and provide insights into the preparation of
multidrug systems.
PMID- 27487265
TI - Liquid Marbles Based on Magnetic Upconversion Nanoparticles as Magnetically and
Optically Responsive Miniature Reactors for Photocatalysis and Photodynamic
Therapy.
AB - Magnetic liquid marbles have recently attracted extensive attention for various
potential applications. However, conventional liquid marbles based on iron oxide
nanoparticles are opaque and inadequate for photo-related applications. Herein,
we report the first development of liquid marbles coated with magnetic lanthanide
doped upconversion nanoparticles (UCNPs) that can convert near-infrared light
into visible light. Apart from their excellent magnetic and mechanical
properties, which are attractive for repeatable tip opening and magnetically
directed movements, the resultant UCNP-based liquid marbles can act as ideal
miniature reactors for photodynamic therapy of cancer cells. This work opens new
ways for the development of liquid marbles, and shows great promise for liquid
marbles based on UCNPs to be used in a large variety of potential applications,
such as photodynamic therapy for accelerated drug screening, magnetically guided
controlled drug delivery and release, and multifunctional actuation.
PMID- 27487266
TI - Network ethnopharmacological evaluation of the immunomodulatory activity of
Withania somnifera.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (Ashwagandha, WS)
is one of the extensively explored Ayurvedic botanicals. Several properties
including immunomodulation, anti-cancer and neuro-protection of the botanical
have been reported. Even though, in indigenous medicine, WS is well known for its
immunomodulatory activity, the molecular mechanism of immunomodulation has not
been elucidated. AIM OF THE STUDY: This study aimed the evaluation of the
immunomodulatory effect of WS using network ethnopharmacology technique to
elucidate the in silico molecular mechanism. MATERIALS AND METHODS: Databases-
DPED, UNPD, PubChem, Binding DB, ChEMBL, KEGG and STRING were used to gather
information to develop the networks. The networks were constructed using
Cytoscape 3.2.1. Data analysis was performed with the help of Excel pivot table
and Cytoscape network analyzer tool. RESULTS: Investigation for WS immune
modulation mechanism identified five bioactives that are capable of regulating 15
immune system pathways through 16 target proteins by bioactive-target and protein
protein interactions. The study also unveils the potential of withanolide
phytosterol combination to achieve effective immunomodulation and seven novel
bioactive-immune target combinations. CONCLUSION: The study elucidated an in
silico molecular mechanism of immunomodulation of WS. It unveils the potential of
withanolide-phytosterol combination to achieve a better immunomodulation.
Experimental validation of the network findings would aid in understanding the
rationale behind WS immunomodulation as well as aid in bioactive formulation
based drug discovery.
PMID- 27487267
TI - Effects of platelet-rich plasma on cartilage regeneration after costal cartilage
resection: a stereological and histopathological study.
AB - BACKGROUND: In cases of congenital chest wall deformities, it is important to
maintain the flexibility of the chest wall after rib cartilage resection. In this
study, we aimed to determine the regeneration capability of cartilage and the
effects of platelet-rich plasma (PRP) on the regeneration process. METHODS: A
total of 16 four-week-old New Zealand rabbits were used in this study. In the 4th
5th right costal cartilages, the perichondrial sheaths were dissected and costal
cartilages were excised. Then, the perichondrial sheaths were closed with
absorbable material in the sham group (n = 8), and this was done after replacing
PRP in the PRP group (n = 8). The left costal cartilages of the animals were used
as controls. The volumes of the costal cartilages and their perichondrial sheaths
were estimated using Cavalieri's principle. In addition, the mean numerical
densities of the chondroblasts and chondrocytes per square millimetre were
estimated using unbiased counting frames. RESULTS: In the PRP and sham groups,
the volumes of the cartilages and perichondrial sheaths were higher than those of
the control group (p < 0.05). The numerical densities of the chondroblasts and
chondrocytes increased more in the PRP group than in the sham group (p < 0.05).
CONCLUSIONS: Applying PRP after resection may provide better healing and faster
regeneration of cartilage.
PMID- 27487268
TI - Developing and sustaining human resources in the health supply chain in Ethiopia:
barriers and enablers.
AB - INTRODUCTION: The health supply chain is often the weakest link in achieving the
health-related Millennium Development Goals and universal health coverage,
requiring trained professionals who are often unavailable. In Ethiopia there have
been recent developments in the area of health supply chain management. The aim
of this study was to explore the current status of the development of human
resources in health supply chain management in Ethiopia and to identify important
factors affecting this development. METHODS: A series of face-to-face interviews
with key stakeholders was carried out in 2014. The interviews were conducted
using a semi-structured interview guide. The interview guide comprised 51
questions. A qualitative analysis of transcripts was made. RESULTS: A total of 25
interviews were conducted. Three themes were identified: General changes:
recognition, commitment and resources, Education and training, and Barriers and
enablers. Results confirm the development of human resources in health supply
chain management in many areas. However, several problems were identified
including lack of coordination, partly due to the large number of stakeholders;
reported high staff mobility; and a lack of overall strategy regarding the
job/career structures necessary for maintaining human resources. Rural areas have
a particular set of problems, including in transportation of goods and personnel,
attracting and keeping personnel, and in communication and access to information.
CONCLUSIONS: Ethiopia is on the way to developing a nationwide viable system for
health supply chain management. However, there are still challenges. Short-term
challenges include the importance of highlighting strategies and programs for
human resources in health supply chain management. In the long term, commitments
to financial support must be obtained. A strategy is needed for the further
development and sustainability of human resources in the health supply chain in
Ethiopia.
PMID- 27487269
TI - Exploring the Motivations for Punishment: Framing and Country-Level Effects.
AB - Identifying the motives underpinning punishment is crucial for understanding its
evolved function. In principle, punishment of distributional inequality could be
motivated by the desire to reciprocate losses ('revenge') or by the desire to
reduce payoff asymmetries between the punisher and the target ('inequality
aversion'). By separating these two possible motivations, recent work suggests
that punishment is more likely to be motivated by disadvantageous inequality
aversion than by a desire for revenge. Nevertheless, these findings have not
consistently replicated across different studies. Here, we suggest that
considering country of origin-previously overlooked as a possible source of
variation in responses-is important for understanding when and why individuals
punish one another. We conducted a two-player stealing game with punishment,
using data from 2,400 subjects recruited from the USA and India. US-based
subjects punished in response to losses and disadvantageous inequality, but
seldom invested in antisocial punishment (defined here as punishment of non
stealing partners). India-based subjects, on the other hand, punished at higher
levels than US-based subjects and, so long as they did not experience
disadvantageous inequality, punished stealing and non-stealing partners
indiscriminately. Nevertheless, as in the USA, when stealing resulted in
disadvantageous inequality, India-based subjects punished stealing partners more
than non-stealing partners. These results are consistent with the hypothesis that
variation in punitive behavior varies across societies, and support the idea that
punishment might sometimes function to improve relative status, rather than to
enforce cooperation.
PMID- 27487270
TI - Thermoelectric properties of monolayer MSe2 (M = Zr, Hf): low lattice thermal
conductivity and a promising figure of merit.
AB - Monolayer transition-metal dichalcogenides (TMDCs) MX2 (M = Mo, W, Zr, Hf, etc; X
= S, Se, Te) have become well-known in recent times for their promising
applications in thermoelectrics and field effect transistors. In this work, we
perform a systematic study on the thermoelectric properties of monolayer ZrSe2
and HfSe2 using first-principles calculations combined with Boltzmann transport
equations. Our results point to a competitive thermoelectric figure of merit
(close to 1 at optimal doping) in both monolayer ZrSe2 and HfSe2, which is
markedly higher than previous explored monolayer TMDCs such as MoS2 and MoSe2. We
also reveal that the higher figure of merits arise mainly from their low lattice
thermal conductivity, and this is partly due to the strong coupling of acoustic
modes with low frequency optical modes. It is found that the figure of merits can
be better optimized in n-type than in p-type. In particular, the performance of
HfSe2 is superior to ZrSe2 at a higher temperature. Our results suggest that
monolayer ZrSe2 and HfSe2 with lower lattice thermal conductivity than usual
monolayer TMDCs are promising candidates for thermoelectric applications.
PMID- 27487271
TI - Differential Effects of E2 on MAPK Activity in the Brain and Heart of Aged Female
Rats.
AB - Aging and the coincident loss of circulating estrogens at menopause lead to
increased risks for neurological and cardiovascular pathologies. Clinical studies
show that estrogen therapy (ET) can be beneficial in mitigating these negative
effects, in both the brain and heart, when it is initiated shortly after the
perimenopausal transition. However, this same therapy is detrimental when
initiated >10 years postmenopause. Importantly, the molecular mechanisms
underlying this age-related switch in ET efficacy are unknown. Estrogen receptors
(ERs) mediate the neuroprotective and cardioprotective functions of estrogens by
modulating gene transcription or, non-genomically, by activating second messenger
signaling pathways, such as mitogen activated protein kinases (MAPK). These
kinases are critical regulators of cell signaling pathways and have widespread
downstream effects. Our hypothesis is that age and estrogen deprivation following
menopause alters the expression and activation of the MAPK family members p38 and
ERK in the brain and heart. To test this hypothesis, we used a surgically induced
model of menopause in 18 month old rats through bilateral ovariectomy (OVX)
followed by an acute dose of 17beta-estradiol (E2) administered at varying time
points post-OVX (1 week, 4 weeks, 8 weeks, or 12 weeks). Age and E2 treatment
differentially regulated kinase activity in both the brain and heart, and the
effects were also brain region specific. MAPK signaling plays an integral role in
aging, and the aberrant regulation of those signaling pathways might be involved
in age-related disorders. Clinical studies show benefits of ET during early
menopause but detrimental effects later, which might be reflective of changes in
kinase expression and activation status.
PMID- 27487275
TI - DNA Methyltransferase 1: A Potential Gene Therapy Target for Hepatocellular
Carcinoma?
AB - BACKGROUND: DNA methyltransferase 1 (DNMT1) mutants display altered methylation
patterns that may contribute to oncogenesis. We hypothesized that the silencing
or inhibition of DNMT1 may affect the malignancy of hepatocellular carcinoma
(HCC) cells. METHODS: The HCC cell line KYN2 was used to construct 3 experimental
groups: i) a DNMT1-siRNA group transfected with a green fluorescent protein (GFP)
lentiviral vector to silence endogenous DNMT1 gene expression, which was
confirmed by real-time quantitative polymerase chain reaction, ii) a 5-Aza-CdR
group transfected with a null GFP lentiviral vector and treated with the DNMT1
inhibitor 5-aza-2'-deoxycytidine (5-Aza-CdR), and iii) a control group
transfected with a null GFP lentiviral vector. Cellomics ArrayScan VTI imaging
and MTT assays were conducted to assess cell proliferation. Cell cycle phase
arrest and apoptosis were assayed by flow cytometry. Colony formation was
assessed by fluorescence microscopy. RESULTS: DNMT1 mRNA expression was
significantly inhibited in DNMT1-silenced cells relative to control cells (p <
0.05), indicating successful transfection and gene expression knockdown. Cell
proliferation was significantly inhibited in DNMT1-siRNA and 5-Aza-CdR cells
relative to control cells (p < 0.05). G1-to-S phase shifts were significantly
increased in DNMT1-siRNA and 5-Aza-CdR cells relative to control cells (p <
0.05). Apoptosis was significantly increased in DMNT1-siRNA and 5-Aza-CdR cells
relative to control cells (p < 0.05). DMNT1-siRNA and 5-Aza-CdR cells displayed
significantly reduced colony formation relative to control cells (p < 0.05).
Notably, 5-Aza-CdR had more pronounced effects upon all these parameters than
DNMT1 silencing. CONCLUSION: DNMT1 activity appears to positively contribute to
the malignancy of HCC cells.
PMID- 27487272
TI - Body Mass Index as a Measure of Obesity: Racial Differences in Predictive Value
for Health Parameters During Pregnancy.
AB - BACKGROUND: As a measure of obesity, body mass index (BMI; kg/m2) is an imperfect
predictor of health outcomes, particularly among African Americans. However, BMI
is used to guide prenatal care. We examined racial differences in the predictive
value of maternal BMI for physiologic correlates of obesity, serum interleukin
(IL)-6 and C-reactive protein (CRP), as well as cesarean section and infant birth
weight. METHODS: One hundred five pregnant women (40 European American, 65
African American) were assessed during the second trimester. BMI was defined as
per prepregnancy weight. Electrochemiluminescence and enzyme-linked immunosorbent
assays were used to quantify IL-6 and CRP, respectively. Birth outcomes were
determined by medical record review. RESULTS: Women of both races classified as
obese had higher serum IL-6 and CRP than their normal-weight counterparts (ps <=
0.01). However, among women with overweight, elevations in IL-6 (p < 0.01) and
CRP (p = 0.06) were observed among European Americans, but not African Americans
(ps >= 0.61). Maternal obesity was a significantly better predictor of cesarean
section among European Americans versus African Americans (p = 0.03) and BMI was
associated with infant birth weight among European Americans (p < 0.01), but not
African Americans (p = 0.94). Effects remained after controlling for gestational
age at delivery, gestational diabetes, and gestational weight gain as
appropriate. CONCLUSIONS: BMI may be a less valid predictor of correlates of
overweight/obesity among African Americans versus European Americans during
pregnancy. This should be considered in epidemiological studies of maternal-child
health. In addition, studies examining the comparative validity of
alternative/complementary measures to define obesity in pregnancy are warranted
to inform clinical care.
PMID- 27487276
TI - Quantitative analysis of lymph nodes in neck dissection specimens. Morphologic
study.
AB - PURPOSE: To quantify the amount of lymph nodes harvested in modified radical neck
dissection. METHODS: Cross-sectional anatomical study conducted in 28 non
preserved cadavers. RESULTS: The mean number of lymph nodes found in each nodal
level of the 56 modified radical neck dissections performed were: level IA - 1.5
(95% CI: 1.1 - 1.8), level IB - 2.5 (95% CI: 2.1 - 2.9), level IIA - 7.2 (95% CI:
6.0 - 8.5), IIB level - 6.5 (95% CI: 5.5 - 7.4), level III - 6.6 (95% CI: 5.7 -
7.4), level IV - 8.6 (95% CI: 7.1 - 10.1), level V - 11 (95% CI: 9.2 - 12.7),
totalizing 43.8 lymph nodes (95% CI: 40.3 - 47.4). CONCLUSION: The results
defined a parameter in relation to the minimum recommended nodal yield in a
modified radical neck dissection, as well as the number of lymph nodes in each
level of this dissection, performed in clinical practice.
PMID- 27487277
TI - Serum concentrations and renal expressions of IL-1 and TNF-a early after
hemorrhage in rats under the effect of glibenclamide.
AB - PURPOSE: To investigate changes in the serum concentration and renal expression
of IL-1 and TNF-alpha cytokines in rats that received sevoflurane and
glibenclamide prior to hemorrhage. METHODS: Two groups of sevoflurane
anesthetized Wistar rats (n=10): G1 (control) and G2 (glibenclamide, 1 ug/g
i.v.); hemorrhage of 30% blood volume (10% every 10 min), with replacement using
Ringer solution, 5 ml/kg/h. Serum concentrations of IL-1 and TNF-alpha were
studied in the first hemorrhage (T1) and 50 min later (T2), renal expression, at
T2. RESULTS: In serum, G1 TNF-alpha (pg/mL) was T1=178.6+/-33.5, T2=509.2+/-118.8
(p<0.05); IL-1 (pg/mL) was T1=148.8+/-31.3, T2=322.6+/-115.4 (p<0.05); in G2, TNF
alpha was T1=486.2+/-83.6, T2=261.8+/-79.5 (p<0.05); IL-1 was T1=347.0+/-72.0,
T2= 327.3+/-90.9 (p>0.05). The expression of TNF-alpha and IL-1 in the glomerular
and tubular cells was significantly higher in the G2 group. CONCLUSIONS:
Hemorrhage and glibenclamide elevated TNF-alpha and IL-1 concentrations in serum
and kidneys. High levels of TNF-alpha already present before the hemorrhage in
the glibenclamide group may have attenuated the damages found in the kidneys
after the ischemia event.
PMID- 27487278
TI - Surgical approach to the thyroarytenoid branch of the inferior laryngeal nerve
through the thyroid cartilage.
AB - PURPOSE: To describe the anatomical course of the intralaryngeal portion of the
inferior laryngeal nerve (ILN) and to standardize the surgical access to its
thyroarytenoid branch (TAb) through the thyroid cartilage. METHODS: Under
surgical microscopy, 33 adult human excised larynges were dissected, to expose
the intralaryngeal portion of ILN. The point of entry of TAb, ILN's terminal
branch, in the thyroarytenoid (TA) muscle was determined and correlated with
thyroid cartilage dimensions. RESULTS: After entering the larynx, the ILN
consistently traveled between the thyroid cartilage and the lateral
cricoarytenoid muscle in an anterior and slightly cranial course. The distance
from the point of entry of the TAb in the TA muscle to the midline (TAb-H) and to
the inferior border (TAb-V) of the thyroid cartilage differed according to
gender. In females, mean distances of TAb-H and TAb-V were 20.5mm and 5.2mm and
in males, 22.3mm and 5.9mm, respectively. CONCLUSION: The intralaryngeal course
of the inferior laryngeal nerve presents low variability and measures from
landmarks in the thyroid cartilage help to estimate the point of entry of
thyroarytenoid branch in thyroarytenoid muscle.
PMID- 27487279
TI - Toll-like receptor 7 involves the injury in acute kidney ischemia/reperfusion of
STZ-induced diabetic rats.
AB - PURPOSE: To determine whether Toll-like receptor 7 (TLR7) is the potential
targets of prevention or progression in the renal ischemia/reperfusion (I/R)
injury of STZ-induced diabetic rats. METHODS: Thirty six Sprague-Dawley rats were
randomly arranged to the nondiabetic (ND) or diabetic group (DM), with each group
further divided into sham (no I/R injury), I/R (ischemia-reperfusion) and CD
(given by Chloroquine) group. Preoperatively, Chloroquine (40 mg/kg,
intraperitoneal injection.) was administrated 6 days for treatment group. I/R
animals were subjected to 25 min of bilateral renal ischemia. Renal function,
histology, apoptosis, cytokines, expression of TLR7, MyD88 and NF-kappaB were
detected. RESULTS: The serum levels of blood urea nitrogen, creatinine, IL-6 and
TNF-alpha, apoptotic tubular epithelial cells, expression of TLR7, MyD88 and NF
kappaB were significantly increased in DM+I/R group, compared with ND+I/R group
(p<0.05). All these changes were further improved by TLR7 inhibition Chloroquine
except Paller scores (p<0.05). CONCLUSION: Toll-like receptor 7 inhibition
attenuates the acute renal ischemia/reperfusion injury of STZ-induced diabetic in
SD rats.
PMID- 27487280
TI - The protective cardiac effects of Beta-myrcene after global cerebral
ischemia/reperfusion in C57BL/J6 mouse.
AB - PURPOSE: To investigate the protective effect of beta-myrcene (MYR) on oxidative
and histological damage in mice heart tissue caused global cerebral
ischemia/reperfusion (IR) in C57BL/J6 mice. METHODS: Animals(n=40) were randomly
divided into four groups: (1)control, (2)IR, (3)MYR and (4)MYR+IR. The control
group was received 0.1% carboxymethyl cellulose as a vehicle following a medial
incision without carotid occlusion. In the IR group, the bilateral carotid
arteries were clipped for 15min, and treated with the vehicle
intraperitoneally(ip) for 10 days. MYR (200mg/kg) was received dissolved in
0.1%CMC for 10 days. In the MYR+IR group, the IR model was applied exactly as in
the IR group, and then they were treated with MYR 10 days. RESULTS: The cerebral
IR caused oxidative damage (increase TBARS, decrease antioxidant parameters).
Treatment of MYR was increased in GSH,GPx,CAT,SOD activity while TBARS level was
decreased. In addition, degenerative changes in I/R group heart tissue were
ameliorated by MYR administration. CONCLUSION: The administration of beta-myrcene
protects oxidative and histological damage in the heart tissue after global
ischemia-reperfusion and may be useful safe alternative treatment for cardiac
tissue after ischemic stroke.
PMID- 27487281
TI - Low intensity ultrasound therapy induces angiogenesis and persistent inflammation
in the chronic phase of the healing process of third degree burn wounds
experimentally induced in diabetic and non-diabetic rats.
AB - PURPOSE: To evaluate the effects of low intensity ultrasound on the healing
process of third degree burn wounds in experimentally induced diabetic Wistar
rats. METHODS: One hundred rats were divided into: control group; non-diabetic
treated group; diabetic control group; diabetic treated group. The therapy was
performed with a 3MHz ultrasound application, pulsed emission at 100Hz frequency,
modulated at 20% with a dosage of 0.5W/cm2 during three minutes throughout 30
days. The surgical debridement of the wound was performed once at day 2. The
wounds were morphometrically, macroscopically and microscopically evaluated at 3,
7, 14, 21 and 30 days. RESULTS: The wound contraction and collagen quantification
were higher in all treated groups. Macroscopically, necrosis was higher in the
diabetic control group. Granulation tissue was higher in treated groups during
the proliferative and remodeling phase. Microscopically, there were greater
mononuclear inflammatory infiltration, angiogenesis and fibroblast quantification
in treated groups during the proliferative and remodeling phases. CONCLUSIONS:
therapeutic ultrasound is beneficial in the inflammatory and proliferative phases
of the healing process because it controlled the necrotic tissue, increased the
granulation tissue and wound contraction. However in the remodeling phase it is
not beneficial because of the continued angiogenesis and a mononuclear
inflammatory infiltration.
PMID- 27487282
TI - The acute effects of preoperative ozone theraphy on surgical wound healing.
AB - PURPOSE: To investigate the effects of preoperative rectal ozone insufflation on
surgical wound healing over the proinflammatory cytokines and histopathological
changes. METHODS: Twenty one rabbits were divided into 3 groups. Sham, surgical
wound, and ozone applied (6 sessions, every other day 70 ug/mL in 12 mL O2-O3
mixture rectally) surgical wound groups were created. TNF-alpha and IL-6 levels
from all rabbits were studied at the basal, 24th hour, and 72nd hour. The
histopathological examination was done by removing the surgical scar tissue at
the end of 72nd hour. RESULTS: TNF-alfa and IL-6 levels were significantly lower
compared to the control group, in the rabbits treated with ozone. The increase in
angiogenesis, the decrease in the number of inflammatory cells, epidermal and
dermal regeneration, better collagen deposition, and increased keratinisation in
stratum corneum were observed in the histopathological examination. It was
determined that the wound healing noticeably accelerated in the ozone group.
CONCLUSION: Preoperative rectal ozone insufflation had a positive effect on
surgical wound healing in acute period.
PMID- 27487283
TI - Measurement of testicular volume in Wistar rats using a caliper and
ultrasonography in experimental surgery.
AB - PURPOSE: To compare the measurement of the testicular volume of Wistar rats using
a caliper and ultrasonography. METHODS: Forty Wistar rats were randomly assigned
into four groups. A tensile force of 1.6 Newton (N) and 1.0 N was applied to the
right spermatic cord in group I and group II, respectively. Group III was the
sham group, and group IV served as a control. The initial and final testicular
volumes were measured using a caliper and ultrasonography and compared. A
significance level of 5% was used. RESULTS: The Kappa coefficient was equal to
0.292 (p = 0.006). The Pearson correlation coefficient obtained for the percent
reduction in the right testicular volume using ultrasonography and a caliper was
equal to 0.696 (p < 0.001). CONCLUSION: There was reasonable agreement and a
significant positive correlation between the percent reduction in the right
testicular volume using ultrasonography and a caliper.
PMID- 27487284
TI - Association between levobupivacaine and pancuronium. Interference in
neuromuscular transmission and blockade in rats.
AB - PURPOSE: To evaluate the effects of levobupivacaine on neuromuscular transmission
and neuromuscular blockade produced by pancuronium in vitro. METHODS: Thirty rats
were distributed into groups (n = 5) according to the drug used alone or in
combination: Group I - levobupivacaine (5 ug.mL-1); Group II - pancuronium (2
ug.mL-1); Group III - pancuronium (2 ug.mL-1) + levobupivacaine (5ug.mL-1). The
following parameters were evaluated: 1) amplitude of diaphragmatic response to
indirect stimulation, before and 60 minutes after the addition of levobupivacaine
and pancuronium alone, and after the addition of levobupivacaine combined with
pancuronium; 2) membrane potentials (MP) and miniature endplate potentials
(MEPP). RESULTS: Levobupivacaine alone did not alter the amplitude of muscle
response and MP. In preparations previoulsy exposed to levobupivacaine, the block
with pancuronium was significantly denser (90.2 +/- 15.2%), showing a significant
difference (p=0.031) in comparison to the block produced by pancuronium alone
(48.9% +/- 9.8%). There was a decrease in the frequency and amplitude of MEPPs.
CONCLUSION: Levobupivacaine potentiated the neuromuscular blockade produced by
pancuronium, confirming a presynaptic action by a decrease in miniature endplate
potentials.
PMID- 27487285
TI - Contamination index. A novel parameter for metal and pesticide analyses in
maternal blood and umbilical cord.
AB - PURPOSE: To evaluate the contamination index of metals and pesticides in pregnant
women, and to relate this to perinatal outcomes. METHODS: Descriptive,
retrospective, exploratory study, developed from existing secondary data analyses
at Level III maternity center. A total of 40 mothers with their newborns (NB),
living in a rural area in Botucatu- Brazil and surrounding region. Blood samples
from mothers and newborn were collected to determine the total contamination
index for metals and pesticides. The concentrations of each metal and each
pesticide were determined in blood samples of mothers and their newborns by
Rudge's results. After obtaining these concentrations, the total contamination
index in mother and NB was calculated, along with its correlation with clinical
parameters of NB. RESULTS: There was no correlation (p> 0.05) between maternal
contamination index with NB clinical parameters, and NB contamination index
versus NB clinical parameters. CONCLUSION: The maternal contamination index of
metals and pesticides was not related to perinatal outcomes, but it could be used
as baseline parameter in future toxicological studies, regarding to long-term
toxic characteristics as persistent organic pollutants, its long half-lives,
bioacumulative, and expected to impose serious health effects on humans.
PMID- 27487286
TI - Morphological and Genetic Diversity of Opisthosporidia: New Aphelid Paraphelidium
tribonemae gen. et sp. nov.
AB - Aphelids are a poorly known group of parasitoids of algae that have raised
considerable interest due to their pivotal phylogenetic position. Together with
Cryptomycota and the highly derived Microsporidia, they have been recently re
classified as the Opisthosporidia, which constitute the sister group to the fungi
within the Holomycota. Despite their huge diversity, as revealed by molecular
environmental studies, and their phylogenetic interest, only three genera have
been described (Aphelidium, Amoeboaphelidium, and Pseudaphelidium), from which
18S rRNA gene sequences exist only for Amoeboaphelidium and Aphelidium species.
Here, we describe the life cycle and ultrastructure of a new representative of
Aphelida, Paraphelidium tribonemae gen. et sp. nov., and provide the first 18S
rRNA gene sequence obtained for this genus. Molecular phylogenetic analysis
indicates that Paraphelidium is distantly related to both Aphelidium and
Amoebaphelidium, highlighting the wide genetic diversity of aphelids.
Paraphelidium tribonemae has amoeboflagellate zoospores containing a lipid
microbody complex, dictyosomes, and mitochondria with rhomboid cristae, which are
also present in trophonts and plasmodia. The amoeboid trophont uses pseudopodia
to feed from the host cytoplasm. Although genetically distinct, the genus
Paraphelidium is morphologically indistinguishable from other aphelid genera and
has zoospores able to produce lamellipodia with subfilopodia like those of
Amoeboaphelidium.
PMID- 27487287
TI - Missing Protein Landscape of Human Chromosomes 2 and 14: Progress and Current
Status.
AB - Within the C-HPP, the Swiss and French teams are responsible for the annotation
of proteins from chromosomes 2 and 14, respectively. neXtProt currently reports
1231 entries on chromosome 2 and 624 entries on chromosome 14; of these, 134 and
93 entries are still not experimentally validated and are thus considered as
"missing proteins" (PE2-4), respectively. Among these entries, some may never be
validated by conventional MS/MS approaches because of incompatible biochemical
features. Others have already been validated but are still awaiting annotation.
On the basis of information retrieved from the literature and from three of the
main C-HPP resources (Human Protein Atlas, PeptideAtlas, and neXtProt), a subset
of 40 theoretically detectable missing proteins (25 on chromosome 2 and 15 on
chromosome 14) was defined for upcoming targeted studies in sperm samples. This
list is proposed as a roadmap for the French and Swiss teams in the near future.
PMID- 27487288
TI - Injustice Experience Questionnaire, Japanese Version: Cross-Cultural Factor
Structure Comparison and Demographics Associated with Perceived Injustice.
AB - OBJECTIVE: The Injustice Experience Questionnaire (IEQ) assesses injury-related
perceived injustice. This study aimed to (1) develop a Japanese version (IEQ-J),
(2) examine its factor structure, validity, and reliability, and (3) discover
which demographic variable(s) positively contributed to prediction of IEQ-J
scores. METHODS: Data from 71 patients (33 male, 38 female; age = 20+) with
injury pain were employed to investigate factor structure by exploratory and
confirmatory factor analyses. Concurrent validity was examined by Pearson
correlation coefficients among the IEQ-J, Brief Pain Inventory (BPI), and Pain
Catastrophizing Scale (PCS). Internal consistency was investigated by Cronbach's
alpha, and test-retest reliability was indicated with intra-class correlations
(ICCs) in 42 of 71 patients within four weeks. Relations between demographic
variables and IEQ-J scores were examined by covariance analysis and linear
regression models. RESULTS: IEQ-J factor structure differed from the original two
factor model. A three-factor model with Severity/irreparability,
Blame/unfairness, and Perceived lack of empathy was extracted. The three-factor
model showed goodness-of-fit with the data and sufficient reliability (Cronbach's
alpha of 0.90 for total IEQ-J; ICCs = 0.96). Pearson correlation coefficients
among IEQ-J, BPI, and PCS ranged from 0.38 to 0.73. Pain duration over a year
(regression coefficient, 11.92, 95%CI; 5.95-17.89) and liability for injury on
another (regression coefficient, 12.17, 95%CI; 6.38-17.96) predicted IEQ-J total
scores. CONCLUSIONS: This study evidenced the IEQ-J's sound psychometric
properties. The three-factor model was the latter distinctive in the Japanese
version. Pain duration over a year and injury liability by another statistically
significantly increased IEQ-J scores.
PMID- 27487289
TI - Third metal stent for revision of malignant hilar biliary strictures.
AB - Background and study aim: Endoscopic stent-in-stent (SIS) placement of multiple
metal stents is technically demanding. In the present study, we explored the
technical feasibility and efficacy of endoscopic deployment of a third metal
stent to create a triple SIS placement in patients with a bilateral SIS
configuration for inoperable high grade malignant hilar biliary stricture (HBS)
that had failed clinically. Methods: Eighteen patients with histologically proven
inoperable HBS underwent deployment of an additional third metal stent as a
revisionary method after early clinical failure following technically successful
bilateral SIS placement using cross-wired metal stents. The main outcome measures
were the technical and clinical success rates, and adverse events. Results: The
overall technical and clinical success rates were 88.9 % (16/18) and 87.5 %
(14/16), respectively. The early and late complications were cholangitis (n = 2)
and cholecystitis (n = 1). Stent occlusion developed in 35.7 % (5/14) of patients
in whom a third metal stent for revision of a bilateral SIS configuration was
clinically successful. The median (range) times for stent patency and patient
survival were 176 days (49 - 372) and 216 days (52 - 384), respectively.
Conclusions: Endoscopic deployment of an additional third metal stent into a
bilateral SIS configuration was technically feasible and effective in patients
with inoperable high grade malignant HBS in whom bilateral SIS placement had
failed clinically.
PMID- 27487290
TI - Synthesis of Surface-Modified Iron Oxides for the Solvent-Free Recovery of
Bacterial Bioactive Compound Prodigiosin and Its Algicidal Activity.
AB - Prodigiosin (PG) is a bioactive compound produced by several bacterial species.
Currently, many technologies are being developed for the production of PG by
fermentation processes. However, new challenges are being faced with regard to
the production of PG in terms of the recovery and purification steps, owing to
the labile nature of PG molecules and the cost of the purification steps.
Conventional methods have limitations due to high cost, low reusability, and
health hazards. Hence, the present investigation was focused on the development
of surface-functionalized magnetic iron oxide ([Fe3O4]F) for solvent-free
extraction of bioactive PG from the bacterial fermented medium. Fe3O4 was
functionalized with diethanolamine and characterized by FT-IR, diffuse
reflectance spectroscopy, thermogravimetric analysis, scanning electron
microscopy, and confocal microscopy. The various process parameters, such as
contact time, temperature, pH, and mass of Fe3O4, were optimized for the
extraction of PG using functionalized Fe3O4. Instrumental analyses confirmed that
the PG molecules were cross-linked with functional groups on [Fe3O4]F through van
der Waals forces of attraction. PG extracted through Fe3O4 or [Fe3O4]F was
separated from the fermentation medium by applying an external electromagnetic
field and regenerated for successive reuse cycles. The purity of the extracted PG
was characterized by high-performance liquid chromatography, FT-IR, and UV
visible spectroscopy. The iron oxide-diethanolamine-PG cross-linked ([Fe3O4]F-PG)
composite matrix effectively deactivates harmful fouling by cyanobacterial growth
in water-treatment plants. The present investigation provides the possibility of
solvent-free extraction of bacterial bioactive PG from a fermented medium using
functionalized magnetic iron oxide.
PMID- 27487291
TI - Synthesis of 2-Vinylindole-3-Acetic Acid Derivatives via Cyanide-Catalyzed Imino
Stetter Reaction.
AB - A new method for the synthesis of 2-vinylindole-3-acetic acid derivatives from
aldimines, which are derived from 2-aminocinnamic acid derivatives and alpha,beta
unsaturated aldehydes, via a cyanide-catalyzed imino-Stetter reaction is
described. Various types of 2-aminocinnamic acid derivatives and alpha,beta
unsaturated aldehydes could be used in this protocol, and the desired 2-vinyl
substituted indole-3-acetic acid derivatives were obtained in high yields. This
cyanide-catalyzed imino-Stetter reaction was further extended to the preparation
of indole-3-acetic acid derivatives bearing a carboxylic acid functionality at
the 2-position, using aldimines obtained from glyoxylates and 2-aminocinnamic
acid derivatives.
PMID- 27487292
TI - Diphenyl Diselenide Reduces Oxidative Stress and Toxicity Caused by HSV-2
Infection in Mice.
AB - Herpes simplex viruses can cause uncommon systemic complications as acute liver
failure (ALT) or urinary tract dysfunctions. Diphenyl diselenide, (PhSe)2 , a
classical studied organic selenium compound, has a novel antiviral action against
HSV-2 infection and well-known antioxidant and anti-inflammatory properties. This
study aimed to investigate if (PhSe)2 reduces oxidative stress and systemic
toxicity caused by HSV-2 infection in mice. Adult BALB/c mice were pre-treated
with (PhSe)2 (5 mg kg-1 /day, intragastric, i.g.) during 5 days; at day 6 mice
were infected with HSV-2 (10 MUl-105 PFU/mL-1 ) and post-treated with (PhSe)2 for
more 5 days. At day 11, they were killed and samples of liver and kidney were
obtained to determine: reactive species (RS); malondialdehyde (MDA), and non
protein thiols (NPSH) levels; the activities of antioxidant enzymes, superoxide
dismutase (SOD), and catalase (CAT). The activities of adenosine deaminase (ADA),
Na+ /K+ -ATPase (liver and kidney); alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and the levels of urea (plasma) were determined as
markers of hepatic and renal toxicity. The results revealed that (PhSe)2
treatment was effective against the increase of renal and hepatic oxidative
stress in infected mice and also normalized hepatic and renal ADA activity. It
recovered the activity of Na+ /K+ - and was not effective against the increase in
urea levels in infected mice. Different from (PhSe)2 , acyclovir (positive
control), caused an increase in ADA activity and a decrease in hepatic CAT
activity. Considering the interest of alternative therapies to treat HSV-2
infections and secondary complications, (PhSe)2 become a notable candidate. J.
Cell. Biochem. 118: 1028-1037, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27487293
TI - First-line sunitinib versus pazopanib in metastatic renal cell carcinoma: Results
from the International Metastatic Renal Cell Carcinoma Database Consortium.
AB - BACKGROUND: Sunitinib (SU) and pazopanib (PZ) are standards of care for first
line treatment of metastatic renal cell carcinoma (mRCC). However, how the
efficacy of these drugs translates into effectiveness on a population-based level
is unknown. PATIENTS AND METHODS: We used the International mRCC Database
Consortium (IMDC) to assess overall survival (OS), progression-free survival
(PFS), response rate (RR) and performed proportional hazard regression adjusting
for IMDC prognostic groups. Second-line OS (OS2) and second-line PFS (PFS2) were
also evaluated. RESULTS: We obtained data from 7438 patients with mRCC treated
with either first-line SU (n = 6519) or PZ (n = 919) with an overall median
follow-up of 40.4 months (95% confidence interval [CI] 39.2-42.1). There were no
significant differences in IMDC prognostic groups (p = 0.36). There was no OS
difference between SU and PZ (22.3 versus 22.6 months, respectively, p = 0.65).
When adjusted for IMDC criteria, the hazard ratio (HR) of death for PZ versus SU
was 1.03 (95% CI 0.92-1.17, p = 0.58). There was no PFS difference between SU and
PZ (8.4 versus 8.3 months, respectively, p = 0.17). When adjusted for IMDC
criteria, the HR for PFS for PZ versus SU was 1.08 (95% CI 0.981-1.19, p = 0.12).
There was no difference in RR between SU and PZ (30% versus 28%, respectively, p
= 0.15). We also found no difference in any second-line treatment between either
post-SU or post-PZ groups for OS2 (13.1 versus 11 months, p = 0.27) and PFS2 (3.7
versus 5.0 months, p = 0.07). CONCLUSIONS: We confirmed in real-world practice
that SU and PZ have similar efficacy in the first-line setting for mRCC and do
not affect outcomes with subsequent second-line treatment.
PMID- 27487294
TI - Metformin and Angiogenesis in Cancer - Revisited.
AB - Several clinical studies demonstrated that diabetic patients treated with
metformin were less likely to develop vascular complications, independent of
glycemic control. It was also demonstrated that the large variety of metformin's
vascular actions can be seen in nondiabetic conditions. Metformin has an
interesting potential to treat vascular dysfunction and tumor angiogenesis in
conditions beyond diabetes. Since metformin's use in cancer as a single
antiangiogenic agent appears to be a therapeutic disappointment, the use of the
drug as part of combination anticancer modality represents a therapeutic
challenge. The normalization of vascular dysfunction as a new therapeutic
strategy may provide better delivery of conventional anticancer agents to the
tumor and disrupted tumor environment. In this review, we will outline the
available information from the literature regarding metformin and tumor
angiogenesis and suggest eventual experimental and clinical approaches.
PMID- 27487295
TI - Fructated apolipoprotein A-I exacerbates cellular senescence in human umbilical
vein endothelial cells accompanied by impaired insulin secretion activity and
embryo toxicity.
AB - Glycation of apolipoproteins is a major feature of the production of
dysfunctional high-density lipoprotein (HDL), which is associated with the
incidence of several metabolic diseases such as coronary artery disease and
diabetes. In this report, fructated apoA-I (fA-I) induced by fructose treatment
showed a covalently multimerized band without cross-linking, and lysine residues
were irreversibly modified to prevent crosslinking. Using pancreatic beta-cells,
insulin secretion was impaired by fA-I in the lipid-free and reconstituted HDL
(rHDL) states, by up to 35%, and 40%, respectively, under hyperglycemic
conditions (25 mmol/L glucose). Treatment of human umbilical vein endothelial
cells (HUVECs) with fA-I and HDL from elderly patients caused a 1.8-fold and 1.5
fold increased cellular senescence, respectively, along with increased lysosomal
enlargement. In the lipid-free and rHDL states, fA-I increased embryo death by
1.5-fold and 2.5-fold, respectively, along with the production of oxidized
species. Furthermore, rHDL containing fA-I (fA-I-rHDL) showed a higher
isoelectric point (pI, approximately 8.5), whereas rHDL containing nA-I (nA-I
rHDL) showed a narrow band range with lower pI (around 8.0) as well as a much
smaller particle size than that of nA-I-rHDL. In conclusion, fructose-mediated
apoA-I fructation resulted in the severe loss of several beneficial functions of
apoA-I and HDL, including anti-senescence and insulin secretion activities,
accompanied with increased susceptibility to protein degradation and structural
modification.
PMID- 27487296
TI - Implementation of the Affordable Care Act and Solid-Organ Transplantation
Listings in the United States.
PMID- 27487297
TI - The salt-regulated element in the promoter of lycopene beta-cyclase gene confers
a salt regulatory pattern in carotenogenesis of Dunaliella bardawil.
AB - In the carotenoid biosynthesis, lycopene beta-cyclase (LCYb) is a key regulatory
enzyme involved in the conversion of lycopene into beta-carotene. Under stress
conditions, such as high salinity, high light, and nutrient deprivation, large
amounts of beta-carotene can be accumulated in Dunaliella bardawil. To study on
the molecular responses of salt stress in D. bardawil is of great significance to
reveal the mechanisms of salt tolerance and engineer crop plants to be salt
tolerant. In this study, the full-length coding sequence of lcyb from D. bardawil
(Dblcyb, GenBank: KX218392) was isolated by transcriptome sequencing. Then the
genomic sequence, promoter and terminator regions of Dblcyb were isolated by
genome walking. The Dblcyb promoter (GenBank: KX218393) contained several typical
transcription boxes, multiple light response elements, and a salt-regulated
element (SRE, GT1GMSCAM4). Dbpsy and Dblcyb responsible for beta-carotene
biosynthesis in D. bardawil was shown to be up-regulated under salt stress, and
their promoters contained the common SRE. By element deletion analysis and using
Ble-EGFP as the reporter, the salt-inducible SRE was confirmed to confer salt
induced expression of Dblcyb promoter. It was indicated that the salt-regulated
expression of Dblcyb may be attributed to the salt-responsive element
(GT1GMSCAM4) and the GT-rich region in its genomic sequence. This article is
protected by copyright. All rights reserved.
PMID- 27487298
TI - Could Borophene Be Used as a Promising Anode Material for High-Performance
Lithium Ion Battery?
AB - The rapid development of electronic products has inspired scientists to design
and explore novel electrode materials with an ultrahigh rate of
charging/discharging capability, such as two-dimensional (2-D) nanostructures of
graphene and MoS2. In this study, another 2-D nanosheet, that is a borophene
layer, has been predicted to be utilized as a promising anode material for high
performance Li ion battery based on density functional theory calculations. Our
study has revealed that Li atom can combine strongly with borophene surface
strongly and easily, and exist as a pure Li(+) state. A rather small energy
barrier (0.007 eV) of Li diffusion leads to an ultrahigh diffusivity along an
uncorrugated direction of borophene, which is estimated to be 10(4) (10(5)) times
faster than that on MoS2 (graphene) at room temperature. A high Li storage
capacity of 1239 mA.h/g can be achieved when Li content reaches 0.5. A low
average operating voltage of 0.466 V and metallic properties result in that the
borophene can be used as a possible anode material. Moreover, the properties of
Li adsorption and diffusion on the borophene affected by Ag (111) substrate have
been studied. It has been found that the influence of Ag (111) substrate is very
weak. Li atom can still bind on the borophene with a strong binding energy of
2.648 eV. A small energy barrier of 0.033 eV can be retained for Li diffusion
along the uncorrugated direction, which can give rise to a high Li diffusivity.
Besides, the performances of borophene-based Na ion battery have been explored.
Our results suggest that an extremely high rate capability could be expected in
borophene-based Li ion battery.
PMID- 27487299
TI - C-Reactive Protein and Inflammatory Cytokines during Percutaneous Coronary
Intervention.
AB - BACKGROUND: C-reactive protein (CRP) is significantly associated with
cardiovascular diseases; however, whether CRP plays a causal role in coronary
artery disease has yet to be determined. In addition, the relationship between
CRP, atherosclerosis, and inflammation remains controversial. METHODS AND
RESULTS: Serum interleukin (IL)-6, IL-1beta, and CRP levels were determined in
160 patients at time points around percutaneous coronary intervention (PCI) with
drug-eluting stent implantation. The levels were found to be at peak at 24 h post
PCI and gradually declined to the level before PCI at day 30 post-PCI. These
inflammation markers around PCI have no statistical difference in the different
postdilation pressures (<=14, 14-18, and >=18 atm) and stent number (1 and >=2
stents) groups. Treatment of cultured human vascular smooth muscle cells (VSMCs)
with a combination of IL-6 and IL-1beta at concentrations associated with PCI did
not result in any significant change in the CRP mRNA levels. The IL-6-augmented
CRP expression in human internal mammary arteries (IMAs) stretched with a
mechanical strength of 3 g was blocked by the nuclear factor-kappaB (NF-kappaB)
peptide inhibitor SN50 and not by the inactive SN50 analog SN50M. IL-6 treatment
increased NF-kappaB activity in human IMAs stretched with 3 g, and this effect
was further blocked by stretch-activated channel (SAC) inhibitors (streptomycin
or GdCl3) and SN50. CONCLUSIONS: The current study provides evidence that
increased serum IL-6, IL-1beta, and CRP levels around PCI are not different
between different postdilation pressure and stent number groups. The combination
of IL-6 and IL-1beta at concentrations associated with PCI cannot induce CRP
expression in human VSMCs, but they can augment mechanical strain-induced CRP
synthesis via the SAC-NF-kappaB pathway in human IMAs.
PMID- 27487300
TI - Effectiveness of Mindfulness-Based Stress Reduction Bibliotherapy: A Preliminary
Randomized Controlled Trial.
AB - OBJECTIVE: This randomized controlled investigation examined the effectiveness of
a self-help bibliotherapy format of the evidence-based mindfulness-based stress
reduction (MBSR) intervention. METHOD: College students seeking stress reduction
were randomly assigned to a 10-week MBSR bibliotherapy intervention group (n =
47) or a no-treatment control group (n = 45). Self-report measures were collected
at baseline and postintervention. RESULTS: A total of 25 bibliotherapy and 43
control group participants provided final data following the intervention period.
Compared to the control group, bibliotherapy participants reported increased
mindfulness following the intervention. Significant decreases on measures of
depression, anxiety, stress, perceived stress, and anxiety sensitivity also were
reported postintervention as well as increased quality of life in physical
health, psychological, and environmental domains. No statistically significant
group effects were found for social relationships quality of life domain, worry,
and experiential avoidance measures. CONCLUSION: This MBSR workbook may provide
an acceptable and effective alternative for motivated individuals seeking to
reduce stress, at least for a select group of individuals who are willing and
able to sustain participation in the intervention.
PMID- 27487301
TI - Corrigendum.
PMID- 27487302
TI - Prior stressor exposure delays the recovery of surgery-induced cognitive
impairment and prolongs neuroinflammation in aged rats.
AB - Increasing evidence indicates that stress potentiates pro-inflammatory response
to a subsequent peripheral immune challenge. The present study investigated if
prior exposure to inescapable tailshock (IS) delayed the recovery of surgery
induced spatial learning and memory impairment and prolonged hippocampus
interleukin (IL)-1beta and IL-6 expression. METHODS: A total of 192 aged rats
were trained with Morris water-maze (MWM) for 6 consecutive days. A single
session of inescapable tailshock was performed on day 6 after training. Then, the
rats subjected to partial hepatectomy. Hippocampal-dependent spatial learning and
memory were assessed on postoperative days 1, 3 and 7. The cytokines IL-1beta and
IL-6 and ionized calcium binding adaptor protein (Iba)-1 were measured at each
time point. Cluster of differentiation 200 (CD200) was also measured to explore
potential mechanisms of glial cell activation. RESULTS: Exposure of IS alone
failed to affect the latency to platform and increase hippocampal cytokine levels
at each time point. However, IS alone significantly increased the expression
levels of Iba-1. A prolonged latency and additional significant increase in
hippocampal levels of IL-1beta and IL-6 were observed when partial hepatectomy
was performed in aged rats exposed to IS 24h later. The combination of IS and
surgical trauma dramatically upregulated the levels of Iba-1 and significantly
decreased the expression of CD200. CONCLUSION: IS alone failed to induce
cognitive deficits and increase pro-inflammatory cytokines expression. However,
IS delayed the recovery of surgery-induced spatial learning and memory impairment
and prolonged pro-inflammatory response to the subsequent surgery challenge.
PMID- 27487303
TI - How Structured Is the Entangled Bank? The Surprisingly Simple Organization of
Multiplex Ecological Networks Leads to Increased Persistence and Resilience.
AB - Species are linked to each other by a myriad of positive and negative
interactions. This complex spectrum of interactions constitutes a network of
links that mediates ecological communities' response to perturbations, such as
exploitation and climate change. In the last decades, there have been great
advances in the study of intricate ecological networks. We have, nonetheless,
lacked both the data and the tools to more rigorously understand the patterning
of multiple interaction types between species (i.e., "multiplex networks"), as
well as their consequences for community dynamics. Using network statistical
modeling applied to a comprehensive ecological network, which includes trophic
and diverse non-trophic links, we provide a first glimpse at what the full
"entangled bank" of species looks like. The community exhibits clear
multidimensional structure, which is taxonomically coherent and broadly
predictable from species traits. Moreover, dynamic simulations suggest that this
non-random patterning of how diverse non-trophic interactions map onto the food
web could allow for higher species persistence and higher total biomass than
expected by chance and tends to promote a higher robustness to extinctions.
PMID- 27487305
TI - Size-specific imprinted polymer embedded carbon nanodots modified magnetic
nanoparticle for specific recognition of titanium nanoparticle: The round versus
round.
AB - Like the two sides of a coin, any new invention or discovery also possess their
two faces. Similarly, while nanomaterials were identified as a boon in several
fields like industrial, medicinal or agriculture; some of them have been also
validated as a risk to the environment and living organisms. In this report, we
addressed an efficient optical method for the detection of popularly used
titanium dioxide nanoparticle (TiO2) by a size-specific imprinted polymer
embedded heteroatom-doped carbon nanodots (CNDs) decorated at the surface of the
water-soluble magnetic nanoparticle. The CNDs were prepared by an economic and
eco-friendly one-step hydrothermal method using a series of Brassicaceae family
members (i.e. radish, cabbage, broccoli, and cauliflower). The as prepared CNDs
shows very good production (12.8%) and quantum yields (40.7%). The size-specific
imprinted polymer is biocompatible and biodegradable in nature and was able to
detect the TiO2 nanoparticles with a high selectivity i.e. limit of detection
(LOD)=6.88ngL(-1) (S/N=3) and remove the nanoparticle very efficiently.
Furthermore, the method was successfully applied for the detection of TiO2
nanoparticles in wastewater, human sera, and cosmetic samples.
PMID- 27487304
TI - Implications of Intraoperative Vascular Surgery Assistance for Hospitals and
Vascular Surgery Trainees.
AB - Importance: Vascular surgeons possess a skill set that allows them to assist
nonvascular surgeons in the operating room. Existing studies on this topic are
limited in their scope to specific procedures or clinical settings. Objective: To
describe the broad spectrum of cases that require intraoperative vascular surgery
assistance. Design, Setting, and Participants: A retrospective medical record
review of patients undergoing nonvascular surgery procedures that required
intraoperative vascular surgery assistance between January 2010 and June 2014 at
a single urban academic medical center (Northwestern Memorial Hospital, Chicago,
Illinois). Trauma patients and inferior vena cava filter placements were
excluded. Exposures: Intraoperative vascular surgery assistance stratified by
need for vascular reconstruction, anatomic location, urgency of consultation, and
timing of consultation. Main Outcomes and Measures: A composite primary end point
of death, myocardial infarction, or unplanned return to the operating room within
30 days of the index operation. Results: We identified 299 patients involving 12
different surgical subspecialties that met the study criteria. The cohort
included 148 men (49.5%) and had a mean (SD) age of 56.4 (15) years. Most
consultations occurred preoperatively (n = 224; 74.9%; odds ratio, 0.04; 95% CI,
0.02-0.08; P < .001) and were elective (n = 212; 70.9%; odds ratio, 0.06; 95% CI,
0.03-0.12; P < .001 ). The indications for vascular surgery assistance were 156
spine exposure (52%), 43 vascular control without hemorrhage (14.4%), 43 control
of hemorrhage (14.4%), and 57 vascular reconstruction (19%). Vascular repairs
consisted of 13 bypasses (4.3%), 18 patch angioplasties (6.0%), and 79 primary
repairs (26.4%). All procedures required open surgical exposure by the vascular
surgeon. The incidence of death, myocardial infarction, or unplanned return to
the operating room was 11.4% for the cohort with a mortality rate of 1.7%.
Patients who required vascular repair had a higher incidence of death, myocardial
infarction, or unplanned return to the operating room (17.4% vs 7.9%; P = .01).
These cases resulted in an additional 1371.46 work relative value units per year.
Conclusions and Relevance: Vascular surgeons provide crucial operative support
across multiple specialties. Although vascular reconstruction is not needed in
most patients, it may be associated with increased risk of death, myocardial
infarction, or unplanned return to the operating room. The high proportion of
emergent cases that require vascular repair demonstrates the importance of having
vascular surgeons immediately available at the hospital. To continue providing
this valuable service, vascular surgery trainees need to continue to learn the
full breadth of open anatomic exposures and vascular reconstruction.
PMID- 27487306
TI - Finding New Components of the Mammalian Immune System.
AB - The use of forward genetics to analyze mammalian biology has been dramatically
accelerated by methods that make it possible instantly to determine which
mutation causes a phenotype. Now it is possible to discover gene function as
rapidly as mutations can be created and screened: approximately 1,000 coding
changes per week are interrogated in our laboratory. Moreover, it is possible to
know approximately how much damage has been done to the genome over time. We
estimate that we have damaged or destroyed about one-quarter of all protein
encoding genes and tested the effects of variant alleles within these genes three
times or more in a set of phenotypic assays that interest us. Only about two
years were required to reach this level of saturation.
PMID- 27487307
TI - For Better Orchiopexy, Processus Vaginalis Should Be Dissected and a High
Ligation Should Be Performed.
AB - OBJECTIVE: Data on the prevalence of patent processus vaginalis (PPV) and hernia
in patients with cryptorchidism are controversial. While some pediatric surgeons
do not dissect the processus vaginalis (PV), most prefer to do so to prevent
hernia formation and to achieve an effective orchiopexy outcome. This study was
performed to evaluate the importance of dissection and high ligation of the PV
during treatment of undescended testis (UT). METHODS: The clinical findings and
surgical procedures of 55 patients with UT were retrospectively investigated.
RESULTS: The mean patient age was 2.5 (range 1.0-12.0) years. Non-palpable testis
(NPT) was located on the right and left side in 39 and 16 patients, respectively.
Ultrasonography revealed no testis in 10 patients and an atrophic testis in 7
patients. Seven patients had a parent with an inguinal hernia, and the silk sign
or a PPV was detected during inguinoscrotal examination in 22 patients.
Undescended testis repair was performed by an inguinal approach in all patients.
The inguinal canal was opened in all patients; 42 patients had a wider-than
normal internal ring (>2.5 cm), and the posterior wall of the inguinal canal was
consequently weakened. Two-stage orchiopexy was performed in 2 patients, and 15
underwent the Prentiss maneuver. In the remaining patients, the dissection was
easily done, and the orchiopexy was performed without any difficulty. Scrotal
edema and wound infection occurred in five and two patients, respectively. One
patient presented with an atrophic testis, and three had recurrent UT. Inguinal
hernia was not observed in any of the patients during the study period, and all
procedures were performed on an outpatient basis. CONCLUSION: High ligation of
the PV is an effective method for successful orchiopexy and prevention of
inguinal hernia in patients with NPT and UT.
PMID- 27487308
TI - Remembering More Jewish Physicians.
AB - The history of medicine has been an intriguing topic for both authors. The modern
relevance of past discoveries led both authors to take a closer look at the lives
and contributions of persecuted physicians. The Jewish physicians who died in the
Holocaust stand out as a stark example of those who merit being remembered. Many
made important contributions to medicine which remain relevant to this day.
Hence, this paper reviews the lives and important contributions of two persecuted
Jewish physicians: Arthur Kessler (1903-2000) and Bronislawa Fejgin (1883-1943).
PMID- 27487309
TI - Acrolein-an alpha,beta-Unsaturated Aldehyde: A Review of Oral Cavity Exposure and
Oral Pathology Effects.
AB - Acrolein is a highly reactive unsaturated aldehyde widely present in the
environment, particularly as a product of tobacco smoke. Our previous studies
indicated the adverse consequences of even short-term acrolein exposure and
proposed a molecular mechanism of its potential harmful effect on oral cavity
keratinocytic cells. In this paper we chose to review the broad spectrum of
acrolein sources such as pollution, food, and smoking. Consequently, in this
paper we consider a high level of oral exposure to acrolein through these sources
and discuss the noxious effects it has on the oral cavity including on salivary
quality and contents, oral resistance to oxidative stress, and stress mechanism
activation in a variety of oral cells.
PMID- 27487310
TI - Effectiveness of Inferior Vena Cava Filters without Anticoagulation Therapy for
Prophylaxis of Recurrent Pulmonary Embolism.
AB - OBJECTIVE: The optimal treatment of deep vein thrombosis (DVT) is anticoagulation
therapy. Inferior vena cava filter (IVC) placement is another option for the
prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This
is used mostly in patients with a contraindication to anticoagulant therapy. The
purpose of the present study was to compare the two options. METHODS: A
retrospective cohort study of two groups of patients with DVT: patients who
received an IVC filter and did not receive anticoagulation due to
contraindications; and patients with DVT and similar burden of comorbidity
treated with anticoagulation without IVC insertion. To adjust for a potential
misbalance in baseline characteristics between the two groups, we performed
matching for age, gender, and Charlson's index, which is used to compute the
burden of comorbid conditions. The primary outcome was an occurrence of a PE.
RESULTS: We studied 1,742 patients hospitalized with the diagnosis of DVT in our
hospital;93 patients from this population received IVC filters. Charlson's score
index was significantly higher in the IVC filter group compared with the
anticoagulation group. After matching of the groups of patients according to
Charlson's score index there were no significant differences in primary outcomes.
CONCLUSION: Inferior vena cava filter without anticoagulation may be an
alternative option for prevention of PE in patients with contraindications to
anticoagulant therapy.
PMID- 27487311
TI - Transversus Abdominis Plane Versus Ilioinguinal and Iliohypogastric Nerve Blocks
for Analgesia Following Open Inguinal Herniorrhaphy.
AB - OBJECTIVES: We hypothesized that preoperative (pre-op) ultrasound (US)-guided
posterior transversus abdominis plane block (TAP) and US-guided ilioinguinal and
iliohypogastric nerve block (ILI+IHG) will produce a comparable analgesia after
Lichtenstein patch tension-free method of open inguinal hernia repair in adult
men. The genital branch of the genitofemoral nerve will be blocked separately.
METHODS: This is a prospective, randomized, controlled, and observer-blinded
clinical study. A total of 166 adult men were randomly assigned to one of three
groups: a pre-op TAP group, a pre-op ILI+IHG group, and a control group. An
intraoperative block of the genital branch of the genitofemoral nerve was
performed in all patients in all three groups, followed by postoperative patient
controlled intravenous analgesia with morphine. The pain intensity and morphine
consumption immediately after surgery and during the 24 hours after surgery were
compared between the groups. RESULTS: A total of 149 patients completed the study
protocol. The intensity of pain immediately after surgery and morphine
consumption were similar in the two "block" groups; however, they were
significantly decreased compared with the control group. During the 24 hours
after surgery, morphine consumption in the ILI+IHG group decreased compared with
the TAP group, as well as in each "block" group versus the control group. Twenty
four hours after surgery, all evaluated parameters were similar. CONCLUSION:
Ultrasound-guided ILI+IHG provided better pain control than US-guided posterior
TAP following the Lichtenstein patch tension-free method of open inguinal hernia
repair in men during 24 hours after surgery. (ClinicalTrials.gov number:
NCT01429480.).
PMID- 27487312
TI - Safety of Completion Thyroidectomy for Initially Misdiagnosed Thyroid Carcinoma.
AB - INTRODUCTION: Completion thyroidectomy is defined as the surgical removal of the
remnant thyroid tissue following procedures of less than total or near-total
thyroidectomy. Whether thyroid reoperations are associated with an increased
complication risk is controversial. OBJECTIVE: A retrospective analysis was done
of patients undergoing completion thyroidectomy for cancer of the thyroid who had
undergone surgery elsewhere for solitary thyroid nodule. The incidence of
surgical complications in these patients after reoperation was investigated in
this study. MATERIAL AND METHODS: The study included a total of 53 patients who
had undergone thyroid lobectomy for a solitary nodule as initial surgery
elsewhere and were referred to our institute for completion thyroidectomy when
the histopathology revealed malignancy. RESULTS: There were 53 patients, 43
females and 10 males. Their mean age was 34.7+/-12.12 years (range 19-65 years).
After initial surgery, the histopathology revealed papillary carcinoma in 46
patients (86.8%), follicular carcinoma in 7 (13.2%). Fourteen out of 53 patients
had recurrent laryngeal nerve palsy after initial surgery (26.4%). None of the
patients had clinical hypocalcemia after the first surgery. One or more
parathyroid glands were identified and preserved in 52 patients (98.1%) in the
process of completion thyroidectomy. No patient had additional recurrent nerve
injury at the second surgery. The mean serum calcium value preoperatively was
8.96+/-0.39 mg/dL, and six months after surgery serum calcium was 8.74+/-0.56
mg/dL. Mean follow-up was 18 months. Transient hypoparathyroidism occurred in
24.5% patients. Five patients were lost to follow-up. Permanent and symptomatic
hyperparathyroidism occurred in eight patients (16.67%). CONCLUSIONS: Completion
thyroidectomy is a safe and appropriate option in the management of well
differentiated thyroid cancer. It removes disease on the ipsilateral and
contralateral side of the thyroid and carries a low risk of recurrent laryngeal
nerve damage, but a higher risk of permanent hypoparathyroidism.
PMID- 27487313
TI - Cancer of the Throat: A Physician's Experience as a Patient.
AB - The author, a practicing physician, was diagnosed with throat cancer and lost his
vocal cords. He endured the side effects of radiation, repeated surgeries, and
the effects of prolonged hospitalizations; confronted medical mistakes and
discrimination after losing his vocal cords; and struggled to regain his speech
and find new meaning and purpose for his life. Facing the hardship and trials of
becoming a laryngectomee illustrated to him how dependent and helpless a patient
can become. Being unable to speak, eat, and breathe normally, while dealing with
a potentially terminal illness, makes the patient very vulnerable, both
physically and emotionally. A skillful, competent, error-free, empathetic, and
caring approach that recognizes what the patient is experiencing can expedite
recovery and well-being and help the patient return to a productive and
meaningful life.
PMID- 27487314
TI - Should Sabbath Prohibitions Be Overridden to Provide Emotional Support to a Sick
Relative?
AB - BACKGROUND: There is a consensus among the halachic authorities that life-saving
actions override Sabbath prohibitions. They are painstaking in securing that the
sanctity of the Sabbath is maintained but that not a single life be lost.
OBJECTIVE: This manuscript examines if and when a relative's presence at the
bedside of a seriously ill individual is potentially life-saving against the
backdrop of the scientific literature. It specifically addresses the
permissibility of traveling in a motorized vehicle, generally prohibited on the
Sabbath, to be with one's relative in hospital for the provision of emotional
support. METHODS: Discourse of the halachic issues in the context of the
scientific literature. RESULTS: Stress, mental or physical, has been determined
as a potentially life-threatening condition in many disease entities. The
literature attests to both the patient's and the professionals' perception of the
curative potential of the presence of loved ones by advocating for the patient
and relieving stress in the hospital experience. Emotional support from a loved
one is perceived by some patients as vital to survival. There is halachic
consensus that a patient's perception of the emotional need for a relative's
presence is sufficient to permit overriding rabbinic prohibitions. Torah
prohibitions, which may be overridden for medical needs, may be overridden for
emotional support, providing a health professional or family member attests to
the fulfilment of this specific need as diminishing the danger to the patient's
life. In certain cases, the latter contingency is unnecessary. CONCLUSIONS:
Emotional support has an impact on the patient's health status; the degree to
which its impact is strong enough to save life is still being studied. As more
data from scientific studies emerge, they may be relevant to sharpening the
halachic rulings with respect to the issue at hand.
PMID- 27487315
TI - The profiles of students with significant cognitive disabilities and complex
communication needs.
AB - Understanding the characteristics of students with complex communication needs
and significant cognitive disabilities is an important first step toward creating
the kinds of supports and services required to help them successfully access the
general education curriculum, achieve grade-level standards, and improve overall
communication competence. The First Contact Survey was designed to collect
important information about students with significant cognitive disabilities who
were eligible to take the Dynamic Learning MapsTM (DLM((r))) alternate assessment
based on alternate achievement standards. From November 2012-May 2013, the survey
was used to gather information regarding more than 44,787 students. At that time,
the goal was to use the data to inform the development of the DLM assessment.
Although the survey includes a wealth of information regarding this large sample
of students, the reanalysis of the data reported in the current study focused on
the motor, sensory, language, reading, and writing skills of students with
significant cognitive disabilities, based on their speech production abilities.
Significant differences were identified across each of the domains between
students who do and do not use speech with or without aided augmentative and
alternative communication.
PMID- 27487316
TI - The Indirect Effect of Perceived Criticism on Suicide Ideation and Attempts.
AB - The effect of perceived criticism from others is one potentially important risk
factor for suicide that has received scant attention, despite decades of research
on the role of criticism in the treatment and course of mental illnesses such as
schizophrenia and mood disorders. This study analyzed the effect of perceived
criticism's association with suicidal ideation and attempts as well as its
connection with the suicide related constructs thwarted belongingness and
perceived burdensomeness as described in the Interpersonal Theory of Suicide.
Fifty participants (66% female, MAge = 18.7), 18 of whom had previously made one
or more suicide attempts, completed a battery of self-report assessments as well
as two in-person, structured clinical interviews. Analyses demonstrated that
perceived parental criticism is a significant indicator of suicide ideation (beta
= .297, p = .003) and attempts (beta = .373, p < .001) and that perceived
criticism from close friends is a significant indicator of suicide attempts (beta
= .297, p = .006). Perceived criticism has a strong indirect effect on suicide
ideation and attempts through its effect on thwarted belongingness, but not
perceived burdensomeness, while controlling for mental illnesses. Some
limitations of this study include the cross-sectional design and the use of a
relatively small, restricted age sample. Treatment designed to mitigate perceived
criticism and thwarted belongingness may be an important component in combatting
suicidal ideation and attempts, particularly among young adults.
PMID- 27487317
TI - Comparison of the National Early Warning Score in non-elective medical and
surgical patients.
AB - BACKGROUND: The National Early Warning Score (NEWS) is used to identify
deteriorating patients in hospital. NEWS is a better discriminator of outcomes
than other early warning scores in acute medical admissions, but it has not been
evaluated in a surgical population. The study aims were to evaluate the ability
of NEWS to discriminate cardiac arrest, death and unanticipated ICU admission in
patients admitted to surgical specialties, and to compare the performance of NEWS
in admissions to medical and surgical specialties. METHODS: Hospitalwide data
over 31 months, from adult inpatients who stayed at least one night or died on
the day of admission, were analysed. The data were categorized as elective or non
elective surgical or medical admissions. The ability of NEWS to discriminate the
outcomes above in these different groups was assessed using the area under the
receiver operating characteristic curve (AUROC). RESULTS: There were too few
outcomes to permit meaningful comparison of elective admissions, so the analysis
was constrained to comparison of non-elective admissions. NEWS performed equally
well, or better, for surgical as for medical patients. For death within 24 h the
AUROC for surgical admissions was 0.914 (95 per cent c.i. 0.907 to 0.922),
compared with 0.902 (0.898 to 0.905) for medical admissions. For the combined
outcome of any of death, cardiac arrest or unanticipated ICU admission, the AUROC
was 0.874 (0.868 to 0.880) for surgical admissions and 0.874 (0.871 to 0.877) for
medical admissions. CONCLUSION: NEWS discriminated deterioration in non-elective
surgical patients at least as well as in non-elective medical patients.
PMID- 27487318
TI - Violence and depression in a community sample.
AB - AIMS AND OBJECTIVES: To understand the relation between the experience of
violence and sociodemographic and clinical factors, and to determine whether
diagnosed depression and the presence of anxiety and stress are related to having
experienced workplace and domestic violence in different genders and age groups.
BACKGROUND: Previous studies indicate that domestic and workplace violence
increase the risk of suffering from depression. However, no studies have
evaluated these two types of violence in a same cohort. DESIGN AND METHODS: We
designed a descriptive cross-sectional study from 317 individuals randomly
selected from the population in southern Catalonia (Spain). Sociodemographic and
Goldberg anxiety-depression questionnaires were administered by telephone survey
to 160 men and 157 women in December 2008. The data obtained were analysed by a
logistic regression model. RESULTS: A quarter of the individuals had suffered
from violence: 48.29% of them had experienced domestic violence and 32.9% had
experienced workplace violence. Nearly half of the individuals with depression
had experienced violence. No statistical difference has been observed between
domestic and workplace violence regarding diagnosed depression. Women were twice
as likely as men to have suffered from violence. People working outside their
home and those who claimed to have no social support had a greater risk of
suffering from violence. A greater consumption of medication, above all of
psychotropic drugs, is associated with experiencing violence and with greater
comorbidity. Predictive factors for suffering from depression are being women,
having experienced violence, having suffered stress or anxiety, having little or
no social support, having overload of task or having no secondary education and
no tertiary education. CONCLUSIONS: This study suggests that when considering
depression, anxiety and stress, especially in women, we must take into account
whether an individual has suffered violence. RELEVANCE TO CLINICAL PRACTICE:
Identifying violence can help health professionals, managers and researchers
improve care and reduce suffering in families and communities.
PMID- 27487319
TI - Synthetic Lipid-Containing Scaffolds Enhance Production by Colocalizing Enzymes.
AB - Subcellular organization is critical for isolating, concentrating, and protecting
biological activities. Natural subcellular organization is often achieved using
colocalization of proteins on scaffold molecules, thereby enhancing metabolic
fluxes and enabling coregulation. Synthetic scaffolds extend these benefits to
new biological processes and are typically constructed from proteins or nucleic
acids. To expand the range of available building materials, we use a minimal set
of components from the lipid-encapsulated bacteriophage phi6 to form synthetic
lipid-containing scaffolds (SLSs) in E. coli. Analysis of diffusive behavior by
particle tracking in live cells indicates that SLSs are >20 nm in diameter;
furthermore, density measurements demonstrate that SLSs contain a mixture of
lipids and proteins. The fluorescent proteins mCitrine and mCerulean can be
colocalized to SLSs. To test for effects on enzymatic production, we localized
two enzymes involved in indigo biosynthesis to SLSs. We observed a scaffold
dependent increase in indigo production, showing that SLSs can enhance the
production of a commercially relevant metabolite.
PMID- 27487320
TI - Reversal of Tetracycline Resistance in Escherichia coli by Noncytotoxic
bis(Tryptophan)s.
AB - Nine bis(tryptophan) derivatives (BTs) and two control compounds were synthesized
and tested for antimicrobial activity against two Escherichia coli strains and a
Staphylococcus aureus strain. The effects of linker type, shape, and
conformational rigidity were manifested in dramatic differences in altering
tetracycline potency when coadministered with that antibiotic. A reversal of
resistance was observed for an E. coli strain having a TetA efflux pump. Survival
of mammalian cells was assayed with good result.
PMID- 27487321
TI - A GDI/GDF-like system for sorting and shuttling ciliary proteins.
AB - Post/co-translational modifications by the addition of lipids take place in a
vast number of proteins. Rab and Rho are small G proteins which are prenylated
and targeted to membranes in complex with solubilizing factors called guanosine
dissociation inhibitors (GDIs). The release of Rab and Rho at the correct
destination from their cognate GDI has been proposed to be mediated through GDI
displacement factors. However this mechanism is yet to be established and it has
been shown that loading of Rab proteins with GTP at the destination can be
sufficient for their correct targeting. PDE6D shares structural homology with Rho
GDI and solubilises several prenylated proteins and mediate their targeting to
different destinations including cilia. In a paper published by Fansa et al, the
authors propose that sorting of cargo is dependent on the differential release by
bona fide GDFs, Arl2 and Arl3, and the localization of the active Arl3GTP in
cilia.
PMID- 27487322
TI - Structural Basis of the Disorder in the Tandem Zinc Finger Domain of the RNA
Binding Protein Tristetraprolin.
AB - Tristetraprolin (TTP) and TIS11d are two human RNA-binding proteins that belong
to the CCCH-type tandem zinc finger family. In the RNA-free state, TIS11d
coordinates a zinc ion in each of its two fingers, while TTP coordinates a single
zinc ion with the N-terminal zinc finger. We have previously identified three
residues, located in the C-terminal half of a short alpha-helix in the second
zinc finger, that control how structured the RNA-binding domain is in these two
proteins: Y151, L152, and Q153 in TTP and H201, T202, and I203 in TIS11d. Here,
we have used molecular dynamics, NMR spectroscopy, and other biochemical methods
to investigate the role of these three residues in the stability of the RNA
binding domain. We found that the intrahelical hydrogen bond formed by the T202
hydroxyl group in the C-terminal zinc finger of TIS11d is necessary to allow for
pi-pi stacking between the side chains of a conserved phenylalanine and the zinc
coordinating histidine. We demonstrated that the lack of this hydrogen bond in
TTP is responsible for the reduced zinc affinity of the C-terminal zinc finger.
PMID- 27487323
TI - Community Pharmacists' Perspectives on Dispensing Medications With the Potential
for Misuse, Diversion, and Intentional Overdose: Results of a Province-Wide
Survey of Community Pharmacists in Canada.
AB - BACKGROUND: Community pharmacists frequently encounter patients at risk of
medication misuse, diversion, and intentional overdose. However, few studies have
examined the perspective of the pharmacist on the identification and management
of these patients. OBJECTIVE: To understand the perspective of community
pharmacists on the dispensing of select medications commonly associated with
misuse, diversion, and overdose. METHODS: An online survey was disseminated by
electronic mail to community pharmacists listed in the College of Pharmacists of
Manitoba directory. The survey was open from July to September 2014. Descriptive
statistics were used to describe demographic information of the pharmacist and
practice setting, and pharmacists' perceptions on the dispensing of select
medications. RESULTS: A total of 82 community pharmacists completed the survey.
Most pharmacists considered a one-month supply appropriate for a psychotropic
agent; but a 7-10 day-supply was considered appropriate for an opioid for acute
pain. Factors that aid pharmacist decisions on providing select medications to
patients include familiarity with the patient, ease of access to medical history
information, and ease of access to the prescribing physician. Only 10.3%, 16.2%,
and 32.4% felt they have received adequate training on the management of patients
at risk for suicide, drug diversion, and medication misuse, respectively.
CONCLUSION: Findings from this study demonstrated a need for improved systems for
managing patients at risk for medication misuse, diversion, and overdose.
Strategies that warrant further attention for limiting the means of medication
misuse include increased access to electronic medical records and providing
additional continuing education support for community pharmacists.
PMID- 27487324
TI - Comparison of Verisyse and Veriflex Phakic Intraocular Lenses for Treatment of
Moderate to High Myopia 36 Months after Surgery.
AB - PURPOSE: To compare refractive stability, endothelial cell count (ECC), incidence
of complications, and patients' satisfaction between a rigid Verisyse (group I, n
= 198) and foldable Veriflex (group II, n = 212) phakic intraocular lenses (pIOL)
over 36 months postop. MATERIALS AND METHODS: This was a retrospective study.
Patients' satisfaction and incidence of photic phenomena were evaluated at one
month and one year postop. Data were analyzed to determine difference between
groups for astigmatism, mean spherical equivalent (MRSE), uncorrected (UDVA) and
corrected (CDVA) monocular distance visual acuity, complication rate (acute and
chronic), and ECC. Differences were considered statistically significant when p <
0.05. RESULTS: Group II cases had significantly higher UDVA, CDVA, and lower
astigmatism during the entire follow-up. There was no significant difference in
mean MRSE or mean ECC postoperatively. In both groups, mean ECC reduced
significantly at one month postop, followed by a gradual linear decline between 1
and 36 months of 22.4 cells/mm2/annum (group I) and 13.32 cells/mm2/annum (group
II). Overall complication rates were <= 10% with no significant inter-group
differences. Group I patients reported lower incidence of halos at one month but
more problems with night vision at one year compared with group II. Overall
satisfaction was high and total incidence of reported photic phenomena was low.
CONCLUSION: Both Verisyse and Veriflex pIOLs are effective in correcting myopia.
The Veriflex lens demonstrated better refractive outcome; however, subclinical
inflammation observed in the Veriflex group and potential influence of
inflammation on ECC loss require further investigation.
PMID- 27487325
TI - Effects of a Single Water Molecule on the Reaction Barrier of Interstellar CO2
Formation Reaction.
AB - The mechanism by which CO2 is formed in the interstellar space remains a mystery.
The most likely reaction is collision between CO and OH; however, previous
theoretical works have shown that the activation barrier for CO2 formation is
high enough to prevent the reaction at the low thermal conditions of space (~10
K). The effects of single water molecule on the reaction barrier of CO2 formation
from reaction between CO and OH have been investigated here by means of ab initio
calculation. The barrier height along the lowest-energy pathway in the reaction
between CO and OH in the absence of the H2O molecule was calculated to be 2.3
kcal/mol when CCSD(T) energy corrections are combined with the MP2 basis set
limit. In the case of the hydrated (H2O-CO-OH) system, the inclusion of a single
H2O molecule into the system significantly decreased the barrier height to 0.2
kcal/mol. This suggests that CO2 can be formed when CO and OH react in the
presence of H2O, even under thermal conditions as low as 10 K.
PMID- 27487326
TI - Computational design strategy: an approach to enhancing the transdermal delivery
of optimal capsaicin-loaded transinvasomes.
AB - The aim of this study was to design and develop simultaneous optimal
transinvasome formulations (OTV) to enhance the transdermal delivery of
capsaicin. Using a central composite experimental design with duplicate
centroids, 10 model formulations of transinvasomes (TVs) were demonstrated. The
lipid compositions of the TV formulations were determined as formulation factors
(Xn) and response variables (Yn), respectively. TV formulations containing a
constant concentration of phosphatidylcholine, cholesterol, 0.15% capsaicin, and
various percentages of d-limonene (X1) and cocamide diethanolamine (X2) were
prepared. The physicochemical characteristics, e.g. the vesicle size, size
distribution, zeta potential, entrapment efficiency, and skin permeability, of
the TV formulations were experimentally investigated. The relationship among the
formulation factor, the response variables, and the OTV was predicted using
Design Expert(r) software. The accuracy and reliability of the OTV predicted
using computer software were experimentally confirmed and investigated as an
experimental transinvasome formulation (ETV). The results indicated that the skin
permeability of the ETV was close to the OTV and was significantly higher than
that of conventional liposomes and commercial products. The response surfaces
estimated by the computer software were helpful in understanding the complicated
relationship among the formulation factor, the response variables, and the
stability of the TV formulation.
PMID- 27487327
TI - Photoinduced Multicomponent Reactions.
AB - The combination of multicomponent approaches with light-driven processes opens up
new scenarios in the area of synthetic organic chemistry, where the need for
sustainable, atom- and energy-efficient reactions is increasingly urgent.
Photoinduced multicomponent reactions are still in their infancy, but significant
developments in this area are expected in the near future.
PMID- 27487328
TI - A genetic assay for gene essentiality in Clostridium.
AB - Essential genes of pathogens are potential therapeutic targets, but are difficult
to verify. Here, gene essentiality was determined by targeted knockout following
engineered gene duplication. Null mutants of candidate essential genes of
Clostridium difficile were viable only in the presence of a stable second copy of
the gene.
PMID- 27487329
TI - Structural and functional characterization of chimeric cyclotides from the Mobius
and trypsin inhibitor subfamilies.
AB - Cyclotides are plant-derived host defense peptides displaying exceptional
stability due to their cyclic cystine knot comprising three intertwined disulfide
bonds and a cyclic backbone. Their six conserved cysteine residues are separated
by backbone loops with diverse sequences. Prototypical cyclotides from the Mobius
(kalata B1) and trypsin inhibitor (MCoTI-II) subfamilies lack sequence homology
with one another, but both are able to penetrate cells, apparently via different
mechanisms. To delineate the influence of the sequences of the loops on the
structure and cell internalization of these two cyclotide subfamilies, a series
of Mobius/trypsin inhibitor loop-chimeras of kalata B1 and MCoTI-II were
synthesized, and structurally and functionally characterized. NMR analysis showed
that the structural fold of the majority of chimeric peptides was minimally
affected by the loop substitutions. Substituting loops 3, 5, or 6 of MCoTI-II
into the corresponding loops of kalata B1 attenuated its hemolytic and cytotoxic
activities, and greatly reduced its cell-penetrating properties. On the other
hand, replacing loops of MCoTI-II with the corresponding loops of kalata B1 did
not introduce cytotoxicity into the chimeras. Loops 2, 3, and 4 of MCoTI-II were
found to contribute little to cell-penetrating properties. Overall, this study
provides valuable insights into the structural basis for the hemolytic,
cytotoxic, and cell-penetrating properties of kalata B1 and MCoTI-II, which could
be useful for future engineering of cyclotides to carry bioactive epitopes to
intracellular targets.
PMID- 27487331
TI - Asymmetric Assembly of All-Carbon Tertiary/Quaternary Nonadjacent Stereocenters
through Organocatalytic Conjugate Addition of alpha-Cyanoacetates to a
Methacrylate Equivalent.
AB - An efficient, highly diastereo- and enantioselective assembly of acyclic carbonyl
fragments possessing nonadjacent all-carbon tertiary/quaternary stereoarrays is
reported based on a Bronsted base catalyzed Michael addition/alpha-protonation
sequence involving alpha-cyanoacetates and 2,4-dimethyl-4-hydroxypenten-3-one as
novel methacrylate equivalent.
PMID- 27487332
TI - Opening of Carborane Cages by Metal Cluster Complexes: The Reaction of a Thiolate
Substituted Carborane with Triosmium Carbonyl Cluster Complexes.
AB - The reaction of Os3(CO)10(NCMe)2 with closo-o-(1-SCH3)C2B10H11 has yielded the
complex Os3(CO)9[MU3-eta(3)-C2B10H9(SCH3)](MU-H)2, 1, by the loss of the two NCMe
ligands and one CO ligand from the Os3 cluster and the coordination of the sulfur
atom and the activation of two B-H bonds with transfer of the hydrogen atoms to
the cluster. Reaction of 1 with a second equivalent of Os3(CO)10(NCMe)2 yielded
the complex Os3(CO)9(MU-H)[(MU3-eta(3)-1,4,5-MU3-eta(3)-6,10,11
C2B10H8S(CH3)]Os3(CO)9(MU-H)2, 2, that contains two triosmium triangles attached
to the same carborane cage. The carborane cage was opened by cleavage of two B-C
bonds and one B-B bond. The B-H group that was pulled out of the cage became a
triply bridging group on one of the Os3 triangles but remains bonded to the cage
by two B-B bonds. When heated to 150 degrees C, 2 was transformed into the
complex Os3(CO)9(MU-H)[(MU3-eta(3)-MU3-eta(3)-C2B10H7S(CH3)]Os3(CO)9(MU-H), 3, by
the loss of two hydrogen atoms and a rearrangement that led to further opening of
the carborane cage. Reaction of 1 with a second equivalent of closo-o-(1
SCH3)C2B10H11 has yielded the complex Os3(CO)6)(MU3-eta(3)-C2B10H9-R-SCH3) (MU3
eta(3)-C2B10H10-S-SCH3)(MU-H)3, 4a, containing two carborane cages coordinated to
one Os3 cluster. Compound 4a was isomerized to the compound Os3(CO)6(MU3-eta(3)
C2B10H9-R-SCH3)(MU3-eta(3)-C2B10H10-R-SCH3)(MU-H)3, 4b, by an inversion of
stereochemistry at one of the sulfur atoms by heating to 174 degrees C.
PMID- 27487333
TI - Designing a heterotrinuclear Cu(II)-Ni(II)-Cu(II) complex from a mononuclear
Cu(II) Schiff base precursor with dicyanamide as a coligand: synthesis, crystal
structure, thermal and photoluminescence properties.
AB - Schiff bases are considered 'versatile ligands' in coordination chemistry. The
design of polynuclear complexes has become of interest due to their facile
preparations and varied synthetic, structural and magnetic properties. The
reaction of the 'ligand complex' [CuL] {H2L is 2,2'-[propane-1,3
diylbis(nitrilomethanylylidene)]diphenol} with Ni(OAc)2.4H2O (OAc is acetate) in
the presence of dicyanamide (dca) leads to the formation of bis(dicyanamido
1kappaN(1))bis(dimethyl sulfoxide)-2kappaO,3kappaO-bis{MU-2,2'-[propane-1,3
diylbis(nitrilomethanylylidene)]diphenolato}
1:2kappa(6)O,O':O,N,N',O';1:3kappa(6)O,O':O,N,N',O'-dicopper(II)nickel(II),
[Cu2Ni(C17H16N2O2)2(C2N3)2(C2H6OS)2]. The complex shows strong absorption bands
in the frequency region 2155-2269 cm(-1), which clearly proves the presence of
terminal bonding dca groups. A single-crystal X-ray study revealed that two [CuL]
units coordinate to an Ni(II) atom through the phenolate O atoms, with double
phenolate bridges between Cu(II) and Ni(II) atoms. Two terminal dca groups
complete the distorted octahedral geometry around the central Ni(II) atom.
According to differential thermal analysis-thermogravimetric analysis (DTA-TGA),
the title complex is stable up to 423 K and thermal decomposition starts with the
release of two coordinated dimethyl sulfoxide molecules. Free H2L exhibits
photoluminescence properties originating from intraligand (pi-pi*) transitions
and fluorescence quenching is observed on complexation of H2L with Cu(II).
PMID- 27487334
TI - Synthesis of 2-(2-hydroxyethyl)-1-(2-hydroxyphenyl)-6,7-dimethoxy-1,2,3,4
tetrahydroisoquinoline and pseudosymmetry in its crystal structure.
AB - Natural and synthetic isoquinoline alkaloids display a wide variety of potent
biological activities. The title 1-aryl-2-hydroxyethyl-1,2,3,4
tetrahydroisoquinoline, C19H23NO4, crystallizes with two molecules in the
asymmetric unit related by pseudo-translation but differing only slightly in
conformation. The pseudosymmetry is also reflected in the diffraction pattern.
The subset of reflections corresponding to the smaller cell and average structure
are on average twice as intense as those subtending the larger cell. Tentative
refinement in the subcell leads to a disordered structural model with
satisfactory agreement factors and, after appropriate use of restraints,
acceptable molecular geometry but significantly larger and more anisotropic
displacement parameters. In the correct unit cell, the independent molecules
differ with respect to the orientation of the hydroxyethyl group. Intramolecular
hydrogen bonding occurs between the hydroxyphenyl group and the N atom.
PMID- 27487330
TI - CXCR5(+) follicular cytotoxic T cells control viral infection in B cell
follicles.
AB - During unresolved infections, some viruses escape immunological control and
establish a persistant reservoir in certain cell types, such as human
immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH
cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we
identified a specialized group of cytotoxic T cells (TC cells) that expressed the
chemokine receptor CXCR5, selectively entered B cell follicles and eradicated
infected TFH cells and B cells. The differentiation of these cells, which we have
called 'follicular cytotoxic T cells' (TFC cells), required the transcription
factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators
Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and,
together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC
cell development. The identification of TFC cells has far-reaching implications
for the development of strategies to control infections that target B cells and
TFH cells and to treat B cell-derived malignancies.
PMID- 27487335
TI - Different acid-base behaviour of a pyrazole and an isoxazole with organic acids:
crystal and molecular structures of the salt 3-(4-fluorophenyl)-1H-pyrazolium
2,4,6-trinitrophenolate and of the cocrystal 4-amino-N-(3,4-dimethyl-1,2-oxazol-5
yl)benzenesulfonamide-3,5-dinitrobenzoic acid (1/1).
AB - Pyrazole and isoxazole rings differ only in the notional replacement of a
potential hydrogen-bond-donor NH unit in pyrazole by a potential hydrogen-bond
acceptor O atom in isoxazole. It is thus of interest to compare the hydrogen
bonding characteristics of these rings. (4-Fluorophenyl)pyrazole undergoes
protonation in the presence of 2,4,6-trinitrophenol to yield the salt 3-(4
fluorophenyl)-1H-pyrazolium 2,4,6-trinitrophenolate, C9H8FN2(+).C6H2N3O7(-), (I),
whereas there is no proton transfer between 4-amino-N-(3,4-dimethyl-1,2-oxazol-5
yl)benzenesulfonamide and 3,5-dinitrobenzoic acid, whose reaction gives the 1:1
cocrystal, C11H13N3O3S.C7H4N2O6, (II). The bond lengths in salt (I) provide
evidence for aromatic-type delocalization in the pyrazolium ring and for
extensive delocalization of the negative charge into the ring of the
trinitrophenolate anion. The O atoms of one of the nitro groups in the
trinitrophenolate anion are disordered over two sets of atomic sites having
occupancies of 0.571 (6) and 0.429 (6), but all of the other substituents on the
carbocyclic rings are fully ordered. The ions in salt (I) are linked by an
extensive series of N-H...O hydrogen bonds to form a three-dimensional framework
structure, and in cocrystal (II), the molecular components are linked by a
combination of O-H...N and N-H...O hydrogen bonds to form complex bilayers.
Comparisons are made with some related compounds.
PMID- 27487336
TI - Unexpected ring-closure products derived from 3-(2-allylanilino)-3-phenylacrylate
esters: crystal and molecular structures of 3-acetyl-8-allyl-6-methyl-2
phenylquinolin-4-yl acetate and (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H
pyrrolo[3,2,1-ij]quinolin-6-one.
AB - The reactions of two 3-(2-allylanilino)-3-phenylacrylate esters with acetic
anhydride and with strong acids has revealed a richly diverse reactivity
providing a number of unexpected products. Thus, acetylation of ethyl 3-(2
allylanilino)-3-phenylacrylate, (Ia), or ethyl 3-(2-allyl-4-methylanilino)-3
phenylacrylate, (Ib), with acetic anhydride yields not only the expected
acetylated esters, (II), as the major products but also the unexpected
polysubstituted quinolines 3-acetyl-8-allyl-2-phenylquinolin-4-yl acetate,
(IIIa), and 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate, (IIIb), as
minor products. Subsequent reaction of the major product ethyl 2-[(2-allyl-4
methylanilino)(phenyl)methylidene]-3-oxobutanoate, (IIb), with concentrated
sulfuric acid did not provide the expected 3-acetylquinoline derivative, but
instead two unexpected products, namely ethyl 4-ethyl-2-phenyl-1,4
dihydroquinoline-3-carboxylate, (IV), and ethyl 3-acetyl-4-ethyl-2-phenyl-3,4
dihydroquinoline-3-carboxylate, (V), in yields of 39 and 22%, respectively. The
reaction of (Ib) with Eaton's reagent gave both the quinoline (Z)-6-methyl-2
phenyl-8-(prop-1-en-1-yl)quinolin-4(1H)-one, (VI), and the unexpected tricyclic
product (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6
one, (VII), in yields of 71 and 12%, respectively. The products (II)-(VII) have
all been fully characterized spectroscopically and the crystal structures of two
of the unexpected products, i.e. (IIIb) (C23H21NO3) and (VII) (C19H17NO), are
reported here. The formation of compounds (IV), (V) and (VII) all require an
isomerization of the initial allyl substituent, with migration of the C=C double
bond from the terminal site to the internal site. In (IIIb), the two acetyl
substituents are oriented such that the intramolecular distance between the two
carbonyl O atoms is only 3.243 (2) A, and in (VII), the five-membered ring adopts
a twisted half-chair conformation. The molecules of compound (IIIb) are linked by
two independent hydrogen bonds to form sheets built from R4(3)(20) rings and the
sheets are linked by a pi-pi stacking interaction to form a three-dimensional
framework structure. The molecules of compound (VII) are linked by a single type
of C-H...O hydrogen bond to form centrosymmetric R2(2)(14) dimers. The molecules
of compound (V), which crystallizes with Z' = 2, are linked by two N-H...O and
two C-H...O hydrogen bonds, forming a chain of rings.
PMID- 27487337
TI - The structure of a valinomycin-hexaaquamagnesium trifluoromethanesulfonate
compound.
AB - Valinomycin is a naturally occurring cyclic dodecadepsipeptide with the formula
cyclo-[D-HiVA->L-Val ->L-LA->L-Val]3 (D-HiVA is D-alpha-hydroxyisovaleic acid,
Val is valine and LA is lactic acid), which binds a K(+) ion with high
selectively. In the past, several cation-binding modes have been revealed by X
ray crystallography. In the K(+), Rb(+) and Cs(+) complexes, the ester O atoms
coordinate the cation with a trigonal antiprismatic geometry, while the six amide
groups form intramolecular hydrogen bonds and the network that is formed has a
bracelet-like conformation (Type 1 binding). Type 2 binding is seen with the
Na(+) cation, in which the valinomycin molecule retains the bracelet conformation
but the cations are coordinated by only three ester carbonyl groups and are not
centrally located. In addition, a picrate counter-ion and a water molecule is
found at the center of the valinomycin bracelet. Type 3 binding is observed with
divalent Ba(2+), in which two cations are incorporated, bridged by two anions,
and coordinated by amide carbonyl groups, and there are no intramolecular amide
hydrogen bonds. In this paper, we present a new Type 4 cation-binding mode,
observed in valinomycin hexaaquamagnesium bis(trifluoromethanesulfonate)
trihydrate, C54H90N6O18.[Mg(H2O)6](CF3SO3)2.3H2O, in which the valinomycin
molecule incorporates a whole hexaaquamagnesium ion, [Mg(H2O)6](2+), via hydrogen
bonding between the amide carbonyl groups and the hydrate water H atoms. In this
complex, valinomycin retains the threefold symmetry observed in Type 1 binding,
but the amide hydrogen-bond network is lost; the hexaaquamagnesium cation is
hydrogen bonded by six amide carbonyl groups. (1)H NMR titration data is
consistent with the 1:1 binding stoichiometry in acetonitrile solution. This new
cation-binding mode of binding a whole hexaaquamagnesium ion by a cyclic
polypeptide is likely to have important implications for the study of metal
binding with biological models under physiological conditions.
PMID- 27487338
TI - 6-Propyl-2-thiouracil versus 6-methoxymethyl-2-thiouracil: enhancing the hydrogen
bonded synthon motif by replacement of a methylene group with an O atom.
AB - The understanding of intermolecular interactions is a key objective of crystal
engineering in order to exploit the derived knowledge for the rational design of
new molecular solids with tailored physical and chemical properties. The tools
and theories of crystal engineering are indispensable for the rational design of
(pharmaceutical) cocrystals. The results of cocrystallization experiments of the
antithyroid drug 6-propyl-2-thiouracil (PTU) with 2,4-diaminopyrimidine (DAPY),
and of 6-methoxymethyl-2-thiouracil (MOMTU) with DAPY and 2,4,6
triaminopyrimidine (TAPY), respectively, are reported. PTU and MOMTU show a high
structural similarity and differ only in the replacement of a methylene group (
CH2-) with an O atom in the side chain, thus introducing an additional hydrogen
bond acceptor in MOMTU. Both molecules contain an ADA hydrogen-bonding site (A =
acceptor and D = donor), while the coformers DAPY and TAPY both show
complementary DAD sites and therefore should be capable of forming a mixed
ADA/DAD synthon with each other, i.e. N-H...O, N-H...N and N-H...S hydrogen
bonds. The experiments yielded one solvated cocrystal salt of PTU with DAPY, four
different solvates of MOMTU, one ionic cocrystal of MOMTU with DAPY and one
cocrystal salt of MOMTU with TAPY, namely 2,4-diaminopyrimidinium 6-propyl-2
thiouracilate-2,4-diaminopyrimidine-N,N-dimethylacetamide-water (1/1/1/1) (the
systematic name for 6-propyl-2-thiouracilate is 6-oxo-4-propyl-2-sulfanylidene
1,2,3,6-tetrahydropyrimidin-1-ide), C4H7N4(+).C7H9N2OS(-).C4H6N4.C4H9NO.H2O, (I),
6-methoxymethyl-2-thiouracil-N,N-dimethylformamide (1/1), C6H8N2O2S.C3H7NO, (II),
6-methoxymethyl-2-thiouracil-N,N-dimethylacetamide (1/1), C6H8N2O2S.C4H9NO,
(III), 6-methoxymethyl-2-thiouracil-dimethyl sulfoxide (1/1), C6H8N2O2S.C2H6OS,
(IV), 6-methoxymethyl-2-thiouracil-1-methylpyrrolidin-2-one (1/1),
C6H8N2O2S.C5H9NO, (V), 2,4-diaminopyrimidinium 6-methoxymethyl-2-thiouracilate
(the systematic name for 6-methoxymethyl-2-thiouracilate is 4-methoxymethyl-6-oxo
2-sulfanylidene-1,2,3,6-tetrahydropyrimidin-1-ide), C4H7N4(+).C6H7N2O2S(-), (VI),
and 2,4,6-triaminopyrimidinium 6-methoxymethyl-2-thiouracilate-6-methoxymethyl-2
thiouracil (1/1), C4H8N5(+).C6H7N2O2S(-).C6H8N2O2S, (VII). Whereas in (I) only an
AA/DD hydrogen-bonding interaction was formed, the structures of (VI) and (VII)
both display the desired ADA/DAD synthon. Conformational studies on the side
chains of PTU and MOMTU also revealed a significant deviation for cocrystals (VI)
and (VII), leading to the desired enhancement of the hydrogen-bond pattern within
the crystal.
PMID- 27487339
TI - A new one-dimensional strontium vanadium tellurite, Sr7V4Te12O41.
AB - Vanadium tellurites display a rich structural chemistry with interesting physical
properties, such as second harmonic generation (SHG). Tellurites, i.e. Te(4+)Ox,
are often observed in unusual structures and form various structural motifs,
including isolated clusters, chains, layers, and three-dimensional networks.
Similarly, vanadates, i.e. V(5+)Ox, show rich structural features, such as VO4
tetrahedra, VO5 square pyramids or trigonal bipyramids, and VO6 octahedra.
Strontium vanadium tellurite, Sr7V4Te12O41, was obtained from the melt of the
solid-state reaction of SrTeO4 and VO2 in a sealed quartz tube as it cooled from
973 K. The crystal structure exhibits a one-dimensional latticework along the a
axis comprised of paired Sr3Te3Ox units, namely Sr6Te6O2x+1, with corner-shared
TeO4 polyhedra - and specifically the Te lone-pair electrons - facing outward in
the bc plane. The Sr6Te6O2x+1 latticework is helical and is layered in the b-axis
direction against sheets of corner-shared VO4 tetrahedra, and is linked in the c
axis direction via individual corner-shared SrO8 square prisms.
PMID- 27487340
TI - A two-dimensional mixed-valence Cu(II)/Cu(I) coordination polymer constructed
from 2-(pyridin-3-yl)-1H-imidazole-4,5-dicarboxylate.
AB - Coordination polymers are a thriving class of functional solid-state materials
and there have been noticeable efforts and progress toward designing periodic
functional structures with desired geometrical attributes and chemical properties
for targeted applications. Self-assembly of metal ions and organic ligands is one
of the most efficient and widely utilized methods for the construction of CPs
under hydro(solvo)thermal conditions. 2-(Pyridin-3-yl)-1H-imidazole-4,5
dicarboxylate (HPIDC(2-)) has been proven to be an excellent multidentate ligand
due to its multiple deprotonation and coordination modes. Crystals of
poly[aquabis[MU3-5-carboxy-2-(pyridin-3-yl)-1H-imidazole-4-carboxylato
kappa(5)N(1),O(5):N(3),O(4):N(2)]copper(II)dicopper(I)],
[Cu(II)Cu(I)2(C10H5N3O4)2(H2O)]n, (I), were obtained from 2-(pyridin-3-yl)-1H
imidazole-4,5-dicarboxylic acid (H3PIDC) and copper(II) chloride under
hydrothermal conditions. The asymmetric unit consists of one independent Cu(II)
ion, two Cu(I) ions, two HPIDC(2-) ligands and one coordinated water molecule.
The Cu(II) centre displays a square-pyramidal geometry (CuN2O3), with two N,O
chelating HPIDC(2-) ligands occupying the basal plane in a trans geometry and one
O atom from a coordinated water molecule in the axial position. The Cu(I) atoms
adopt three-coordinated Y-shaped coordinations. In each [CuN2O] unit,
deprotonated HPIDC(2-) acts as an N,O-chelating ligand, and a symmetry-equivalent
HPIDC(2-) ligand acts as an N-atom donor via the pyridine group. The HPIDC(2-)
ligands in the polymer serve as T-shaped 3-connectors and adopt a MU3
kappa(2)N,O:kappa(2)N',O':kappaN''-coordination mode, linking one Cu(II) and two
Cu(I) cations. The Cu cations are arranged in one-dimensional -Cu1-Cu2-Cu3-
chains along the [001] direction. Further crosslinking of these chains by HPIDC(2
) ligands along the b axis in a -Cu2-HPIDC(2-)-Cu3-HPIDC(2-)-Cu1- sequence
results in a two-dimensional polymer in the (100) plane. The resulting (2,3)
connected net has a (12(3))2(12)3 topology. Powder X-ray diffraction confirmed
the phase purity for (I), and susceptibilty measurements indicated a very weak
ferromagnetic behaviour. A thermogravimetric analysis shows the loss of the
apical aqua ligand before decomposition of the title compound.
PMID- 27487341
TI - A More Accurate Approach to Amyloid Detection and Subtyping: Combining in situ
Congo Red Staining and Immunohistochemistry.
AB - Amyloidosis is the result of various, differently approachable diseases. It is
vital to subtype the amyloid deposits in order to establish and finally treat the
underlying disease properly. Besides the classical staining with Congo red,
further procedures like immunohistochemical staining are needed for
classification. Here, we present a more accurate approach using Congo
red/immunohistochemical double staining easily applicable in routine diagnostics.
Modifications of the Congo red staining technique and the immunohistochemical
procedures were needed in order to combine both staining procedures on one slide.
The evaluation was done using conventional light and fluorescence microscopy. By
shortening the staining time for Congo red to 10 s and by modification regarding
endogenous peroxidase blockage, accurate results could be obtained for evaluating
the Congo red/immunohistochemistry double staining using a fluorescence
microscope. Sections of 2 MUm instead of 4 MUm thickness were superior for
evaluation, since they increased staining specificity. The combination of Congo
red and immunohistochemistry as in situ double staining on one slide is a
feasible approach in the diagnosis of amyloidosis. It allows focusing on the
fluorescent Congo red-positive areas when evaluating immunohistochemistry, thus
avoiding signing out false-positive results. Additionally, it increases the
signal-to-noise ratio of the immunohistochemically stained sections on
conventional microscopy.
PMID- 27487342
TI - Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH
1-37.
AB - BACKGROUND/AIMS: Parathyroid hormone (PTH) derivatives exert pronounced renal and
osteoanabolic properties when given intermittently. The current study was
performed to assess the pharmacokinetic and pharmacodynamic properties as well as
safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy
subjects. METHODS: This randomized, double-blind, dose-escalating, placebo and
active comparator controlled study was conducted in 33 healthy postmenopausal
women. Subjects were allocated to one of five treatment options: 10, 20, or 40 ug
PTH-1-37, 20 ug PTH-1-34 or placebo, administered as once daily subcutaneous
doses for three days. Plasma drug concentrations and serum levels of endogenous
PTH-1-84, and calcium as markers of biological activity were monitored during the
treatment. RESULTS: PTH was absorbed rapidly from the subcutaneous tissue with a
median tmax of 30 minutes for 20 and 40 ug of PTH-1-37. tmax was 45 minutes for
20 ug PTH-1-34. Elimination half-lives were estimated as 76 +/- 34 min and 70 +/-
13 min for 20 ug and 40 ug PTH-1-37 (mean +/- SD), and 78 +/- 34 for 20 ug PTH-1
34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1
37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH
1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the
study period, the subjects experienced no unexpected or serious adverse events.
CONCLUSIONS: PTH-1-37 is rapidly absorbed after s.c. injection, has a short
plasma elimination half-life, and does not accumulate during multiple dosing.
Biological activity was demonstrated by rising serum calcium and decreasing
endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and
safe. Our investigation presents data that PTH-1-37 is an excellent drug
candidate for intervening with syndromes of dysregulation of calcium metabolism.
PMID- 27487343
TI - Funduscopic versus HRT III Confocal Scanner Vertical Cup-Disc Ratio Assessment in
Normal Tension and Primary Open Angle Glaucoma (The Leuven Eye Study).
AB - PURPOSE: To compare funduscopic and confocal scanning vertical cup-disc ratio
(VCDR) assessments and their respective predictive value for estimating
functional glaucomatous damage. METHODS: Data from a single eye of open angle
glaucoma patients from the Leuven Eye Study were included: age, gender, intra
ocular pressure, visual acuity, refractive error, visual field mean deviation and
pattern standard deviation, funduscopic and HRT III VCDRs as well as mean retinal
nerve fibre layer thickness. Non-parametric tests to compare differences within
and between diagnostic groups were used, and receiver-operating characteristic
curves as well as Bland-Altman plots constructed. RESULTS: Three hundred and one
eyes of 301 subjects with primary open angle glaucoma (POAG) and normal tension
glaucoma (NTG) were included. The average VCDR assessed with HRT III was
significantly smaller than the funduscopic measurement (0.69 +/- 0.16 vs. 0.81 +/
0.14, respectively; p < 0.001). The predictive value of both measurement
techniques did not differ in NTG patients, but the funduscopic estimate yielded a
significantly larger predictive power in patients with severe POAG. CONCLUSION:
Funduscopic and confocal scanner estimates of VCDR differ significantly and
should not be used interchangeably. In POAG patients with severe glaucoma, a
subjective VCDR predicts functional glaucomatous damage significantly better.
PMID- 27487344
TI - Glioblastoma Multiforme with Hypodipsic Hypernatremia in a Seven-Month-Old Golden
Retriever.
AB - Primary hypodipsic hypernatremia is a rarely reported disease in dogs. Reported
underlying causes associated with this disease in dogs include congenital
malformations, encephalitis, intracranial neoplasia, and pressure atrophy of the
hypothalamus secondary to hydrocephalus. The dog in this report had an
infiltrative neoplastic disorder, likely causing damage to the hypothalamic
osmoreceptors responsible for the thirst generation. The neoplastic process was
identified histopathologically as glioblastoma multiforme, an unusual tumor to
occur in a dog this young. A tumor of the central nervous system causing physical
destruction of the osmoreceptors has rarely been reported in dogs and none of the
previously reported cases involved a glial cell tumor.
PMID- 27487345
TI - Evaluation of Dogs with Border Collie Collapse, Including Response to Two
Standardized Strenuous Exercise Protocols.
AB - Clinical and metabolic variables were evaluated in 13 dogs with border collie
collapse (BCC) before, during, and following completion of standardized strenuous
exercise protocols. Six dogs participated in a ball-retrieving protocol, and
seven dogs participated in a sheep-herding protocol. Findings were compared with
16 normal border collies participating in the same exercise protocols (11
retrieving, five herding). Twelve dogs with BCC developed abnormal mentation
and/or an abnormal gait during evaluation. All dogs had post-exercise elevations
in rectal temperature, pulse rate, arterial blood pH, PaO2, and lactate, and
decreased PaCO2 and bicarbonate, as expected with strenuous exercise, but there
were no significant differences between BCC dogs and normal dogs.
Electrocardiography demonstrated sinus tachycardia in all dogs following
exercise. Needle electromyography was normal, and evaluation of muscle biopsy
cryosections using a standard panel of histochemical stains and reactions did not
reveal a reason for collapse in 10 dogs with BCC in which these tests were
performed. Genetic testing excluded the dynamin-1 related exercise-induced
collapse mutation and the V547A malignant hyperthermia mutation as the cause of
BCC. Common reasons for exercise intolerance were eliminated. Although a genetic
basis is suspected, the cause of collapse in BCC was not determined.
PMID- 27487346
TI - Perioperative Cefovecin to Reduce the Incidence of Urinary Tract Infection in
Dogs Undergoing Hemilaminectomy.
AB - The prevalence of urinary tract infections (UTIs) in dogs with Type I
intervertebral disc extrusion has been reported as high as 38% within 6 wk of
surgery. Proper treatment of a UTI is important with myelopathy because it is a
risk factor for persistent infection and reinfection in dogs. The study authors'
investigated the incidence of UTIs in dogs having received either cefovecin or
cefazolin as a preoperative prophylactic antibiotic for thoracolumbar
hemilaminectomy. Thirty-nine dogs were retrospectively identified and assigned to
groups based on preoperative antibiotic administration and postoperative urinary
tract management. Urinalysis and urine culture performed preoperatively, at 2 wk,
and at 6 wk, were reviewed to determine the incidence of UTIs. Urinary tract
management, grade of neurologic deficit, time to ambulation, and time to
voluntary urination were identified to evaluate for additional risk factors. No
significant prevalence of UTI incidence was appreciated between the cefovecin and
cefazolin groups. Patients with higher grades of neurologic deficit and that took
longer to regain ambulation and voluntary urination were at significantly greater
risk for UTIs throughout the postoperative period. This study reemphasizes the
importance of continued surveillance for UTIs in patients with prolonged
neurologic recovery.
PMID- 27487347
TI - Diagnosis and Outcome of Periosteal Chondrosarcoma in Two Cats.
AB - Two cats, both over 10 yr old, were presented for evaluation of non-painful bony
proliferations on the appendicular skeleton. These proliferations were
identifiable via palpation. Radiographs showed a smooth, proliferative bony
lesion of the distal femur (case 1) and tarsus (case 2) with mild soft tissue
swelling. Surgical debulking with incomplete resection was performed in each cat.
Subsequent histopathology resulted in a diagnosis of periosteal chondrosarcoma
(PC). Although both cats have experienced local recurrence, both are still alive
more than 2.5 yr after mass debulking. Periosteal chondrosarcoma is a
differential diagnosis in proliferative cortical bony lesions near an articular
surface in older cats. Partial resection of these masses can lead to an excellent
quality of life, and proper diagnosis can avoid amputation or even euthanasia.
PMID- 27487348
TI - Evaluation of Commonly Used Products for Disinfecting Clipper Blades in
Veterinary Practices: A Pilot Study.
AB - Nosocomial infections are a concern of growing interest in veterinary medicine.
Clipper blades have been confirmed as fomites for numerous potential pathogens
and, as such, may be associated with wound and surgical site infections. The goal
of this study was to evaluate the disinfectant capabilities of several commonly
used clipper blade cleaning products. Seventy sterile clipper blades were
inoculated with strains of Pseudomonas aeruginosa , Escherichia coli , and
Staphylococcus aureus . Blades were then subjected to one of seven treatment
groups for disinfecting. Quantitative cultures of remaining bacteria were
performed. All blades in the control group showed large amounts of bacterial
recovery. Culture results showed no recovery in blades soaked in alcohol or
chlorhexidine or those sprayed with an ethanol/o-phenylphenol product, while
moderate recovery was seen with all other treatments. These results show that
persistent contamination of clipper blades can occur with the use of several
commonly used disinfectant products. Further research is necessary to evaluate
fungicidal capabilities as well as the effect of disinfection on clipper blade
maintenance.
PMID- 27487349
TI - Chronic Vomiting in Cats: Etiology and Diagnostic Testing.
AB - Chronic vomiting in cats is a common presenting problem seen in veterinary
practice today. The initial step when presented with a vomiting patient is to
differentiate between vomiting and regurgitation or dysphagia. There are numerous
causes for chronic vomiting in cats, and therefore a detailed and comprehensive
patient history and a systematic diagnostic approach are key steps in determining
the cause for vomiting and the most appropriate treatment plan. Common causes for
chronic vomiting in cats may include inflammatory bowel disease, food allergy,
gastrointestinal motility disorders, neoplasia, and extra-gastrointestinal
diseases, such as renal disease, hepatobiliary disease, and hyperthyroidism.
PMID- 27487350
TI - Seminal Vesiculitis in Three Pet Rabbits ( Oryctolagus cuniculus ).
AB - To date, descriptions of pathologic conditions of the seminal vesicle in rabbits
are scarce and limited to the laboratory animals in experimental conditions. The
present article describes three cases of strangury, abdominal pain, and anorexia
associated with seminal vesiculitis in pet rabbits. Three non-neutered male pet
rabbits aged 3.6, 1.5, and 2.1 yrs were presented with strangury, abdominal pain,
and anorexia. Seminal vesiculitis was diagnosed based on clinical signs and
ultrasonography findings. Vesiculectomy was performed in two cases that presented
strangury refractory to medical treatment, and diagnosis was confirmed by
histopathology. In the third case, the patient received medical treatment, and a
sequela in the form of lithiasis of the seminal vesicle was detected 3 yrs later.
Plain radiographs were nearly unremarkable, and results from complete blood
analysis and urinalysis were not specific in all three cases. Contrast
radiography was performed in one case, showing a dilated seminal vesicle.
Ultrasound and surgical biopsy seem to be the most sensitive techniques in the
diagnosis of this pathology. Seminal vesiculitis must be included in the
differential diagnosis of acute or chronic strangury in male pet rabbits.
PMID- 27487351
TI - Palliative Epineurotomy for Focal Radial Malignant Peripheral Nerve Sheath Tumor
in a Dog.
AB - This case report describes the diagnosis of a peripheral nerve sheath tumor of
the deep branch of the radial nerve distal to the elbow in a dog. The lesion was
identified using computed tomography and ultrasonography and confirmed as sarcoma
on histopathological analysis of incisional biopsies. Clinical signs dramatically
improved following surgical biopsy before recurring three months later. Repeat
epineurotomy of the deep branch of the radial nerve resulted in clinical
improvement for a further month before signs once again returned. Epineurotomy as
a palliative treatment for peripheral nerve sheath tumors has not been previously
described, but may have a place in palliation of clinical signs in specific cases
of peripheral nerve sheath tumors in which limb amputation is not an option.
PMID- 27487352
TI - Hemothorax in Three Dogs with Intrathoracic Extracardiac Hemangiosarcoma.
AB - Intrathoracic extracardiac hemangiosarcoma (HSA) is rare in dogs. This report
describes three dogs with acute onset dyspnea due to hemorrhagic pleural effusion
resulting from intrathoracic extracardiac masses, which were confirmed as HSA by
histopathology. The dogs were stabilized with thoracocentesis and intravascular
fluid resuscitation. Computed tomography identified intrathoracic masses, which
were not originating from the heart or pulmonary parenchyma. Surgical exploration
was performed in all cases. Case 1 was euthanized intraoperatively as the tumor
could not be dissected from the aorta. In cases 2 and 3, hemostasis and resection
of the tumors was successful. Case 2 was euthanized 1 mo after surgery and case 3
was alive at the time of writing, 5 mo postoperatively. Intrathoracic
extracardiac HSA should be considered as a differential for nontraumatic
hemothorax and surgical treatment can be palliative.
PMID- 27487353
TI - Modern Spirometry Supports Anesthetic Management in Small Animal Clinical
Practice: A Case Series.
AB - Modern spirometry, like no other monitoring technique, allows insight into breath
to-breath respiratory mechanics. Spirometers continuously measure volume, airway
pressure, and flow while calculating and continuously displaying respiratory
system compliance and resistance in the form of loops. The aim of this case
series is to show how observation of spirometric loops, similar to
electrocardiogram or CO2 curve monitoring, can improve safety of anesthetic
management in small animals. Spirometric monitoring cases described in this case
series are based on use of the anaesthesia monitor Capnomac Ultima with a side
stream spirometry sensor. The cases illustrate how recognition and understanding
of spirometric loops allows for easy diagnosis of iatrogenic pneumothorax,
incorrect ventilator settings, leaks in the system, kinked or partially
obstructed endotracheal tube, and spontaneous breathing interfering with
intermittent positive-pressure ventilation. The case series demonstrates the
potential of spirometry to improve the quality and safety of anesthetic
management, and, hence, its use can be recommended during intermittent positive
pressure ventilation and procedures in which interference with ventilation can be
expected.
PMID- 27487354
TI - Upper Airway Injury in Dogs Secondary to Trauma: 10 Dogs (2000-2011).
AB - Ten dogs that presented with trauma-induced upper airway rupture or stenosis were
reviewed. Tracheal rupture was seen in seven dogs, tracheal stenosis in one dog,
and laryngeal rupture in two dogs. Clinical abnormalities included respiratory
distress in five dogs, subcutaneous emphysema in eight, air leakage through the
cervical wound in seven, stridor in three dogs, pneumomediastinum in four and
pneumothorax in one dog. Reconstruction with simple interrupted sutures was
performed in four dogs, tracheal resection and end-to-end anastomosis in five
dogs, and one dog was euthanized intraoperatively. Complications were seen in
three dogs including aspiration pneumonia in one and vocalization alterations in
two dogs.
PMID- 27487355
TI - Copeptin levels and kidney function in ADPKD: case-control study.
AB - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
common hereditary kidney disease. Studies have suggested a possible prognostic
role of copeptin in determining the rate of progressive kidney function decline
in ADPKD patients. However, it remains unresolved whether the changes in copeptin
levels are specific for ADPKD or merely reflect a decline in glomerular
filtration rate (GFR) regardless of the etiology of chronic kidney disease (CKD).
METHODS: We performed a case-control study in ADPKD and non-ADPKD (control)
patients. Patients were categorized based on the GFR-category (G-stage, KDIGO).
We evaluated urea, creatinine, cystatin C, and copeptin in plasma and correlated
these levels with estimated glomerular filtration rate (eGFR) (CKD-EPI). All p
values were two sided, and p < 0.05 was considered as statistically significant.
RESULTS: We enrolled 112 ADPKD and 112 control patients. The median copeptin
level was 10.72 (interquartile range (IQR) 5.21 - 26.21) pmol/L in the ADPKD
group and 12.32 (IQR 4.47 - 30.73) pmol/L in the control group. The median
copeptin level increased according to the G-stage in a progressive fashion and
remained statistically significant across all G-stages and in both groups.
Copeptin levels were not significantly different between ADPKD and control
groups. We found a significant inverse correlation between copeptin level and
eGFR (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) in the ADPKD,
r = -0.81 (p < 0.001), and in the control group, r = -0.76 (p < 0.001).
CONCLUSIONS: Copeptin levels seem to be strongly correlated with renal function
rather than the presence of ADPKD. Further prospective studies need to evaluate
its role as a prognostic marker in the early stage of CKD for ADPKD progression.
PMID- 27487358
TI - Intrusion of a Liquid Droplet into a Powder under Gravity.
AB - Intrusion of a liquid droplet into a hexagonal close-packed array of spheres
under gravity is investigated using analytical methods and volume-of-fluid
simulations. Four regimes of ultimate fluid behavior are identified: (A) no
liquid imbibition into the bed, (B) trapping of liquid high in the bed, (C)
liquid descending to the bottom of the bed, and (D) liquid spreading around the
surface of all particles. These regimes are mapped based on the contact angle and
Bond number of the system. Many aspects of the dynamics and ultimate liquid
behavior are captured using a simplified model of a mass of liquid moving under
gravity in a vertical capillary of undulating cross-sectional area. This
simplified model is used to form momentum transport equations with four forms of
nondimensional time, which are shown to collapse the simulation data with
different fluid parameters in different regimes.
PMID- 27487357
TI - Medication Intervention for Chronic Kidney Disease Patients Transitioning from
Hospital to Home: Study Design and Baseline Characteristics.
AB - BACKGROUND: The hospital readmission rate in the population with chronic kidney
disease (CKD) is high and strategies to reduce this risk are urgently needed.
METHODS: The CKD-Medication Intervention Trial (CKD-MIT; www.clinicaltrials.gov;
NCTO1459770) is a single-blind (investigators), randomized, clinical trial
conducted at Providence Health Care in Spokane, Washington. Study participants
are hospitalized patients with CKD stages 3-5 (not treated with kidney
replacement therapy) and acute illness. The study intervention is a pharmacist
led, home-based, medication management intervention delivered within 7 days after
hospital discharge. The primary outcome is a composite of hospital readmissions
and visits to emergency departments and urgent care centers for 90 days following
hospital discharge. Secondary outcomes are achievements of guideline-based
targets for CKD risk factors and complications. RESULTS: Enrollment began in
February 2012 and ended in May 2015. At baseline, the age of participants was 69
+/- 11 years (mean +/- SD), 50% (77 of 155) were women, 83% (117 of 141) had
hypertension and 56% (79 of 141) had diabetes. At baseline, the estimated
glomerular filtration rate was 41 +/- 14 ml/min/1.73 m2 and urine albumin-to
creatinine ratio was 43 mg/g (interquartile range 8-528 mg/g). The most frequent
diagnosis category for the index hospital admission was cardiovascular diseases
at 34% (53 of 155), but the most common single diagnosis for admission was
community-acquired acute kidney injury at 10% (16 of 155). CONCLUSION:
Participants in CKD-MIT are typical of acutely ill hospitalized patients with
CKD. A medication management intervention after hospital discharge is under study
to reduce post-hospitalization acute care utilization and to improve CKD
management.
PMID- 27487356
TI - Downstream Antisense Transcription Predicts Genomic Features That Define the
Specific Chromatin Environment at Mammalian Promoters.
AB - Antisense transcription is a prevalent feature at mammalian promoters. Previous
studies have primarily focused on antisense transcription initiating upstream of
genes. Here, we characterize promoter-proximal antisense transcription downstream
of gene transcription starts sites in human breast cancer cells, investigating
the genomic context of downstream antisense transcription. We find extensive
correlations between antisense transcription and features associated with the
chromatin environment at gene promoters. Antisense transcription downstream of
promoters is widespread, with antisense transcription initiation observed within
2 kb of 28% of gene transcription start sites. Antisense transcription initiates
between nucleosomes regularly positioned downstream of these promoters. The
nucleosomes between gene and downstream antisense transcription start sites carry
histone modifications associated with active promoters, such as H3K4me3 and
H3K27ac. This region is bound by chromatin remodeling and histone modifying
complexes including SWI/SNF subunits and HDACs, suggesting that antisense
transcription or resulting RNA transcripts contribute to the creation and
maintenance of a promoter-associated chromatin environment. Downstream antisense
transcription overlays additional regulatory features, such as transcription
factor binding, DNA accessibility, and the downstream edge of promoter-associated
CpG islands. These features suggest an important role for antisense transcription
in the regulation of gene expression and the maintenance of a promoter-associated
chromatin environment.
PMID- 27487359
TI - Potential Curative Role of Hypericum Perforatum in an Experimental Rat Model of
Tympanic Membrane Perforation.
AB - OBJECTIVE: Our aim was to investigate the curative role of topical Hypericum
perforatum (HP) in a rat model of tympanic membrane perforation in a
histopathological manner. MATERIALS AND METHODS: This study was conducted on 30
female Sprague-Dawley rats. An HP extract was prepared as a suspension in pure
olive oil. In all rats, the right and left tympanic membranes were perforated by
a fine puncture under a microscope. Rats were randomly assigned to three groups.
The HP extract was given as drops on a daily basis in Group 1, while olive oil
alone was given on a daily basis in Group 2. In Group 3, the rats were allowed
spontaneous recovery without any intervention. Three rats from each group were
sacrificed on days 7, 14, and 21. Temporal bullae were removed for
histopathological examination to evaluate fibroblast proliferation, leukocyte
infiltration, neovascularization, and subepithelial thickness and to compare
these among the groups. RESULTS: In histopathological examination of the rats
from each group on days 7, 14, and 21, there were significant differences in
leukocyte infiltration, fibroblast proliferation, and subepithelial thickness. No
significant difference was observed in neovascularization among the groups.
CONCLUSION: Compared with the spontaneous recovery group, HP was found to be more
effective in a wound-healing model of the tympanic membrane. HP may be applied in
clinical practice if it is shown to be safe with regard to ototoxicity.
PMID- 27487360
TI - Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective
Enough?
AB - OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng
(KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND
METHODS: The first part of the study was conducted on the House Ear Institute
Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and
their combination for 24 h. Cell viability, apoptosis, and the expression of 84
apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar
albino rats were divided into five groups. Baseline distortion product
otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements
were obtained. In groups I, II, and III, only saline, KRG, and CDDP,
respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of
KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP
injections were administered on day 11. On day 14, final DPOAEs and ABR
measurements were completed. The rats were then sacrificed, and their inner ear
structures were evaluated by transmission electron microscopy. RESULTS: In the
first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP
ototoxicity. This protection was mainly due to a decline in apoptotic gene
expression and an increase in antiapoptotic gene expression. In the in vivo part
of the study, we found that both KRG doses had otoprotective effects. This
protection was more prominent at the lower dose, especially on the spiral
ganglion and the brainstem. CONCLUSION: KRG was shown to be an otoprotective
agent against CDDP-induced ototoxicity both in vivo and in vitro.
PMID- 27487361
TI - Neurofibroma around the Ear Canal: Report of Three Cases.
AB - Facial nerve neurofibromas are an uncommon entity, particularly in the
intraparotid region. Three cases are presented herein, including the first
reported case of both an intratemporal and intraparotid facial nerve malignant
neurofibroma. To the best of our knowledge, this is the first medical publication
to describe a neurofibroma involving both the intratemporal and intraparotid
regions. The aim of this clinical record was to present the surgical experiences
in three cases of intratemporal and intraparotid facial neurofibroma. Of the
three cases of neurofibroma included in this report, the first case was a 30-year
old male who initially presented with a parotid mass without facial dysfunction.
The other two cases were intratemporal neurofibromas, one of which was confirmed
as a plexiform neurofibroma by pathology. These tumors often involve two or more
segments of the facial nerve. The outcomes of these tumors are closely related to
nerve integrity, preoperative facial nerve function level, and the follow-up
period. Neurofibromas are most commonly found with neurofibromatosis type 1 and
are characterized by incorporation of the nerve fibers within their matrix.
Presentation of the intratemporal facial neurofibromas is variable, with facial
palsy most common. Furthermore, the incidence of a solitary neurofibroma of the
facial nerve originating in the parotid region is extremely low.
PMID- 27487362
TI - Cochlear Implantation in Patient with Cochlear Nerve Deficiency: A Case Report.
AB - Diagnostic imaging methods are very important for patients with bilateral
sensourinoural hearing loss. Magnetic resonance imaging (MRI) is able to
demonstrate the vestibulocochlear nerve and facial nerve in the internal acoustic
canal. Also computed tomography can be helpful to determination of the deficiency
of the cochlear nerve. Cochlear nerve anomalies are classified into three group
according to the magnetic resonance imagings. Patients who have cochlear nerve
deficiency may not hear with cochlear amplifications. Auditory brain stem implant
(ABI) is most suitable for these cases. In this case report, we presented a 3
years old girls with bilateral totally hearing loss who performed cochlear
implantation despite of cochlear nerve deficiency on magnetic resonance imaging
(MRI) and computed tomography (CT).
PMID- 27487364
TI - Ceruminous Adenocarcinoma of External Auditory Canal: A Case Report.
AB - The external auditory canal contains ceruminous glands, which are modified
apocrine sweat glands, along with sebaceous glands. Tumors that originate from
ceruminous glands are very rare; thus, the classification, clinical behavior, and
management of these tumors remain debatable. Here we present a case of ceruminous
adenocarcinoma arising from the external auditory canal. Although most authors
advise more aggressive therapy, our patient was treated with local en bloc
resection of the tumor followed by intensity modulated radiotherapy and had no
recurrence for 3 years. We suggest that limited surgery with safe margins
followed by radiotherapy is an alternative choice of treatment in selected
patients with ceruminous adenocarcinoma. Further reports are required to support
this outcome.
PMID- 27487363
TI - An Unusual Presentation of Gout: Tophi in the Middle Ear.
AB - Gout is a common metabolic disease and is characterized by episodic acute and
chronic arthritis caused by the deposition of monosodium urate (MSU) crystals in
joints and connective tissues. The most commonly involved joint is the first
metatarsophalangeal joint. It may also present with nonspecific complaints caused
by gouty tophi in unusual sites of the body such as the spine, bone, and middle
ear. Such involvements can be disabling and impair the quality of life. In this
report, we describe the case of a patient who had complaints of hearing loss and
otorrhea. A 34 year-old male patient presented with complaints of recurrent
otorrhea and hearing loss for several months. He had no history of joint pain or
constitutional symptoms at the time of admission. An otoscopic examination of the
left ear revealed subtotal tympanic membrane perforation, and white middle ear
plaques were detected. The patient underwent intact canal mastoidectomy under
general anesthesia, and middle ear sclerosis was determined as Wieling Kerr
classification type 2. Postoperative histopathologic examination of the specimen
revealed amorphous eosinophilic deposits within fibrous stroma and tophi
containing negatively birefringent MSU crystals by polarized light. After the
histopathologic diagnosis of gout, the patient was assessed for peripheral joint
involvement. He had no radiographic abnormalities. The patient was administered a
serum urate-lowering therapy, given a low purine diet, and followed with the
diagnosis of tophaceous gout. Unusual localizations of gouty tophi have been
reported in the literature. Gouty tophi should also be considered in the
differential diagnosis of middle ear masses alongside common pathologies.
PMID- 27487366
TI - Comparative analysis of the efficacy of low- and moderate-intensity statins in
Korea.
AB - PURPOSE: The American College of Cardiology/American Heart Association (ACC/AHA)
guidelines are based on studies with a limited number of Asian subjects;
therefore, they are difficult to apply to Asian patients, including Korean
patients. MATERIALS AND METHODS: Data were extracted from the clinical data
warehouse system of Seoul St. Mary's hospital (January 2010 - December 2012) to
determine the percent change in low-density lipoprotein cholesterol (LDL-C)
levels at an average 3 and 6 months from baseline. Statins with statistically
similar lowering effects were placed in one group (group A, B, or C). The
proportions of patients who achieved LDL-C < 100 mg/dL were compared between
baseline LDL-C levels: low (< 130 mg/dL), medium (130 - 160 mg/dL), and high (>
160 mg/dL). RESULTS: The majority of the 9 statins of various doses (2,349
patients) were effective at 3 months, with additional, smaller decreases at 6
months. The LDL-C lowering effect of group A (atorvastatin (20 mg), rosuvastatin
(10 mg)) was ~ 45%; that of group B (atorvastatin (10 mg), pitavastatin (2 mg),
pravastatin (40 mg), simvastatin (20 mg)) was 35 - 37%. groups A and B contained
only moderate-intensity statins (ACC/AHA guidelines). With baseline LDL-C >= 130
mg/dL, greater proportions of patients achieved LDL-C < 100 mg with atorvastatin
(20 mg) and rosuvastatin (10 mg). CONCLUSION: Because of the demonstrated LDL-C
lowering effects and target achievement rates, the ACC/AHA guidelines might not
apply to Korean patients. Korean treatment guidelines should consider statins
with relatively low potency. Additional studies regarding appropriate statin
doses should be conducted with Asian populations.
PMID- 27487365
TI - Cell-Autonomous and Non-Cell-Autonomous Regulation of a Feeding State-Dependent
Chemoreceptor Gene via MEF-2 and bHLH Transcription Factors.
AB - Food and feeding-state dependent changes in chemoreceptor gene expression may
allow Caenorhabditis elegans to modify their chemosensory behavior, but the
mechanisms essential for these expression changes remain poorly characterized. We
had previously shown that expression of a feeding state-dependent chemoreceptor
gene, srh-234, in the ADL sensory neuron of C. elegans is regulated via the MEF-2
transcription factor. Here, we show that MEF-2 acts together with basic helix
loop-helix (bHLH) transcription factors to regulate srh-234 expression as a
function of feeding state. We identify a cis-regulatory MEF2 binding site that is
necessary and sufficient for the starvation-induced down regulation of srh-234
expression, while an E-box site known to bind bHLH factors is required to drive
srh-234 expression in ADL. We show that HLH-2 (E/Daughterless), HLH-3 and HLH-4
(Achaete-scute homologs) act in ADL neurons to regulate srh-234 expression. We
further demonstrate that the expression levels of srh-234 in ADL neurons are
regulated remotely by MXL-3 (Max-like 3 homolog) and HLH-30 (TFEB ortholog)
acting in the intestine, which is dependent on insulin signaling functioning
specifically in ADL neurons. We also show that this intestine-to-neuron feeding
state regulation of srh-234 involves a subset of insulin-like peptides. These
results combined suggest that chemoreceptor gene expression is regulated by both
cell-autonomous and non-cell-autonomous transcriptional mechanisms mediated by
MEF2 and bHLH factors, which may allow animals to fine-tune their chemosensory
responses in response to changes in their feeding state.
PMID- 27487367
TI - Expert consensus on the use of liraglutide in the treatment of diabetes in
internal medicine.
AB - BACKGROUND: Type 2 diabetes mellitus (DM2) is a disease of epidemic proportions.
In the adult Spanish population, prevalence of DM2 is nearly 14%, which makes its
monitoring and treatment imperative. Liraglutide has achieved relevance due to
its efficacy and safety in DM treatment. The aim of this study is to gather
expert opinion on diabetes to assess the current role of liraglutide in DM2.
MATERIALS/METHODS: The survey was performed by 57 internal medicine specialists
using the Delphi method. The questionnaire had 56 items regarding liraglutide in
DM treatment. RESULTS: Consensus was reached in 71.4% of items. Panelists stated
agreement regarding liraglutide suitability in the treatment of patients with
DM2, high cardiovascular risk, and with pathologies related to obesity,
highlighting its role in weight loss, low risk of hypoglycemia, and improvement
of vascular risks. Moreover, consensus was not reached regarding the suitability
of liraglutide in patients with special situations, mainly due to minimal
experience caused by the small number of patients. CONCLUSIONS: Due to its safety
and hypoglycemic efficacy, liraglutide is an excellent choice for DM treatment in
combination with other drugs. Its effects on the reduction of weight and other
cardiovascular risk factors, make it an optimal treatment, especially in
overweight or obese patients.
PMID- 27487368
TI - Persistence with antipsychotics in dementia patients in Germany?.
AB - BACKGROUND/AIMS: To analyze the duration of treatment with antipsychotics in
German dementia patients. METHODS: This study included patients aged 60 years and
over with dementia who received a first-time antipsychotic prescription by
psychiatrists between 2009 and 2013. The main outcome measure was the treatment
rate for more than 6 months following the index date. RESULTS: A total of 12,979
patients with dementia (mean age 82 years, 52.1% living in nursing homes) were
included. After 2 years of follow-up, 54.8%, 57.2%, 61.1%, and 65.4% of patients
aged 60 - 69, 70 - 79, 80 - 89, and 90 - 99 years, respectively, received
antipsychotic prescriptions. 63.9% of subjects living in nursing homes and 55.0%
of subjects living at home also continued their treatment (p-value < 0.001).
CONCLUSION: The percentage of dementia patients treated with antipsychotics is
very high.?.
PMID- 27487369
TI - Neurodegeneration with brain iron accumulation.
PMID- 27487370
TI - Postural instability and falls are more frequent in Parkinson's disease patients
with worse trunk mobility.
AB - OBJECTIVE: Correlate the occurrence of falls and the activity of rolling over in
bed with performance on the Trunk Mobility Scale (TMS) in patients with PD, and
determine whether this instrument score can predict the risk of falls. METHOD:
This is a cross-sectional study. Assessed patients reported the frequency of
falls in the previous year and whether they had difficulties rolling over in bed.
Then, the following scales were applied: TMS, Hoehn and Yahr, Unified Parkinson's
Disease Rating Scale-III and Schwab and England Activities of Daily Living.
RESULTS: Eighty-five patients were analyzed. Patients with a history of falling
showed worse performance in the TMS (p < 0.01). There is a significant
correlation between TMS and the activity of rolling over in bed (p < 0.01).
CONCLUSION: PD fallers present worse scores in TMS, and there is a significant
correlation between difficulty rolling over in bed and TMS score.
PMID- 27487371
TI - Household task demands for quiet and focused behavior facilitate performance by
ADHD youth.
AB - This study evaluated the associations among symptoms of attention
deficit/hyperactivity disorder (ADHD) and of oppositional defiant disorder (ODD)
in children and adolescents' performance in household tasks and assistance
provided by caregivers. Parents of children from 6 to 14 years old with ADHD (n =
67) were interviewed with the Children Helping Out: Responsibilities,
Expectations, and Supports (CHORES) instrument. Significant correlations were
found between symptoms of ODD and assistance in self-care tasks (r = -0.31; p =
0.01); symptoms of hyperactivity correlated with assistance in self-care (r =
0.30, p = 0.01); and family-care (r = -0.25, p = 0.04) tasks. Age was directly
associated with the number of tasks performed by children and inversely related
to the assistance provided by caregivers. A greater number of ODD symptoms
resulted in more household assistance from caregivers. Characteristics of ODD
symptoms, such as disobedience and hostility in the face of authority, may limit
these children in accessing household tasks by their own initiative, requiring
assistance from caregivers.
PMID- 27487372
TI - Relationship between muscle strength and motor function in Duchenne muscular
dystrophy.
AB - OBJECTIVE: To investigate the relationship between muscle strength and motor
function and between these variables and age. METHOD: Muscle strength was
measured by Medical Research Council (MRC) scale and motor function, by Motor
Function Measure (MFM), in 40 non-ambulatory patients. Spearman tests
investigated the relationships between muscle strength, motor function and age.
RESULTS: Total MRC and MFM scores were strongly related to each other (r = 0.94;
p < 0.001), but not to age (r = -0.19, r = -0.31, respectively; p > 0.05). Strong
and moderate relationships between partial muscle strength and motor function
scores were found. Higher correlation coefficients were found between total
scores and Dimensions 2 (axial/ proximal control) and 3 (distal control) of MFM.
CONCLUSION: Muscle strength and motor function are strongly correlated and seem
to decrease proportionally in DMD.
PMID- 27487373
TI - Clinical electroencephalogram (EEG) evaluation is improved by the amplitude
asymmetry index.
AB - OBJECTIVE: Better definition of normal amplitude asymmetry values on the
classical EEG frequency bands. RESULTS: EEG amplitude asymmetry index (AAI) is
physiologically low in normal adults, differences usually lesser than 7%.
CONCLUSION: Persistent or intermittent amplitude asymmetry regional differences
higher than 7% may be suggestive of pathology after adequate correlation with
clinical data and EEG classical visual analysis.
PMID- 27487374
TI - Prolactinomas may have unusual presentations resulting from massive extrasellar
tumor extension.
AB - The purpose of this case series is to report eight patients with giant
prolactinomas emphasizing presentations and a treatment complication. The study
group included six men and two women. The median age was 29 years (18-54 years);
median serum prolactin level was 4,562 ng/ml (1,543-18,690 ng/ml); three patients
(37.5%) had panhypopituitarism; median tumor diameter was 50 mm (41-60 mm). Five
patients (62.5%) had visual field defects and three had improvement during
treatment; six patients (75%) reached prolactin normalization, with a median time
of 10.5 months (7-84 months) and median dose of 2.0 mg/week (1.0 to 3.0 mg/week).
One patient presented as a true incidentaloma. One patient presented a
cerebrospinal fluid leakage during medical treatment and refused surgery, however
this resolved with conservative measures. This case series illustrate a rare
subtype of macroprolactinomas, the importance of considering unusual
presentations at the diagnosis, the effectiveness of pharmacological treatment
and its possible complications.
PMID- 27487375
TI - Assessment of impairment in activities of daily living in mild cognitive
impairment using an individualized scale.
AB - Mild impairment in activities of daily living (ADL) can occur in Mild Cognitive
Impairment (MCI), but the nature and extent of these difficulties need to be
further explored. The Canadian occupational performance measure (COPM) is one of
the few individualized scales designed to identify self-perceived difficulties in
ADL. The present study investigated impairments in ADL using the COPM in elderly
with MCI. A total of 58 MCI patients were submitted to the COPM for studies of
its validity and reliability. The COPM proved a valid and consistent instrument
for evaluating ADL in elderly MCI patients. A total of 74.6% of the MCI patients
reported difficulties in ADL. Of these problems, 41.2% involved self-care, 31.4%
productivity and 27.4% leisure. This data further corroborates recent reports of
possible functional impairment in complex ADL in MCI.
PMID- 27487377
TI - Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith.
AB - Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in
people with intractable epilepsy. Probably, optimization of seizure control will
prevent some of these deaths. Briefly, we integrated in this paper some data
about the epidemiology, risk factors, etiology, and preventative measures in the
management of SUDEP.
PMID- 27487376
TI - Translation and cross cultural adaptation of the Pediatric Motor Activity Log
Revised scale.
AB - OBJECTIVES: To translate PMAL-R and adapt for the Brazilian culture; analyze the
reliability and the internal consistency of the Brazilian version. METHOD:
Translation of PMAL-R to the Portuguese-Brazil and back translation. The back
translated version was revised by the authors of the scale. The final version was
administered to a sample of 24 patients with spastic hemiparesis CP between 2-8
years. RESULTS: The reliability intra and inter-rater were suitable (how often =
0.97 and 0.98, how well = 0.98 and 0.99 respectively) and so the internal
consistency (0.98). CONCLUSION: The Brazilian version of PMAL-R has adequate
internal consistency, reliability intra and inter raters and can be used to
assess the spontaneous use of the upper limb of children with CP type spastic
hemiparesis, aged 2-8 years.
PMID- 27487378
TI - Currents issues in cardiorespiratory care of patients with post-polio syndrome.
AB - METHOD: A search for papers was made in the databases Bireme, Scielo and Pubmed
with the following keywords: post polio syndrome, cardiorespiratory and
rehabilitation in English, French and Spanish languages. Although we targeted
only seek current studies on the topic in question, only the relevant (double
blind, randomized-controlled and consensus articles) were considered. RESULTS AND
DISCUSSION: Certain features of PPS such as generalized fatigue, generalized and
specific muscle weakness, joint and/or muscle pain may result in physical
inactivity deconditioning obesity and dyslipidemia. Respiratory difficulties are
common and may result in hypoxemia. CONCLUSION: Only when evaluated and treated
promptly, somE patients can obtain the full benefits of the use of respiratory
muscles aids as far as quality of life is concerned.
PMID- 27487379
TI - Endoscopic endonasal management of cerebrospinal fluid rhinorrhea after anterior
clinoidectomy for aneurysm surgery: changing the paradigm of complication
management.
AB - Resection of the anterior clinoid process results in the creation of the clinoid
space, an important surgical step in the exposure and clipping of clinoidal and
supraclinoidal internal carotid artery aneurysms. Cerebrospinal fluid rhinorrhea
is an undesired and potentially serious complication. Conservative measures may
be unsuccesful, and there is no consensus on the most appropriate surgical
treatment. Two patients with persistent transclinoidal CSF rhinorrhea after
aneurysm surgery were successfully treated with a combined endoscopic
transnasal/transeptal binostril approach using a fat graft and ipsilateral
mucosal nasal septal flap. Anatomical considerations and details of the surgical
technique employed are discussed, and a management plan is proposed.
PMID- 27487380
TI - A diagnostic approach for neurodegeneration with brain iron accumulation:
clinical features, genetics and brain imaging.
AB - Neurodegeneration with brain iron accumulation (NBIA) represents a heterogeneous
and complex group of inherited neurodegenerative diseases, characterized by
excessive iron accumulation, particularly in the basal ganglia. Common clinical
features of NBIA include movement disorders, particularly parkinsonism and
dystonia, cognitive dysfunction, pyramidal signs, and retinal abnormalities. The
forms of NBIA described to date include pantothenase kinase-associated
neurodegeneration (PKAN), phospholipase A2 associated neurodegeneration (PLAN),
neuroferritinopathy, aceruloplasminemia, beta-propeller protein-associated
neurodegeneration (BPAN), Kufor-Rakeb syndrome, mitochondrial membrane protein
associated neurodegeneration (MPAN), fatty acid hydroxylase-associated
neurodegeneration (FAHN), coenzyme A synthase protein-associated
neurodegeneration (CoPAN) and Woodhouse-Sakati syndrome. This review is a
diagnostic approach for NBIA cases, from clinical features and brain imaging
findings to the genetic etiology.
PMID- 27487381
TI - Lumbago and alopecia in a patient with leukodystrophy: think on CARASIL.
PMID- 27487382
TI - Electronically Pure Single-Chirality Semiconducting Single-Walled Carbon Nanotube
for Large-Scale Electronic Devices.
AB - Single-walled carbon nanotube (SWCNT) networks deposited from a purple single
chirality (6,5) SWCNT aqueous solution were electrically characterized as pure
semiconductors based on metal/semiconductor/metal Schottky contacts using both
complex instruments and a portable device. Both air-stable PMOS (p-type metal
oxide-semiconductor) and NMOS (n-type metal-oxide-semiconductor, resembling
amorphous silicon) thin film transistors were fabricated on (6,5) SWCNT in large
scale showing the characteristics of fA off current and ION/IOFF ratio of >1 *
10(8). CMOS (complementary metal-oxide-semiconductor) SWCNT inverter was
demonstrated by wire-bonding PMOS (6,5) SWCNT TFT and NMOS (6,5) SWCNT TFT
together to achieve the voltage gain as large as 52.
PMID- 27487383
TI - HRMS in DMPK.
PMID- 27487384
TI - HRMS or HRAMS?
PMID- 27487385
TI - Unconjugated payload quantification and DAR characterization of antibody-drug
conjugates using high-resolution MS.
AB - AIM: The application of high-resolution MS to antibody-drug conjugate (ADC) drug
development may provide insight into their safety and efficacy. Quantification of
unconjugated cytotoxic drug (payload) and characterization of drug-to-antibody
ratio distribution were determined in plasma using orthogonal acceleration
quadrupole-time-of-flight MS. RESULTS: Unconjugated payload quantification
determined by quadrupole-time-of-flight-based MRM(highresolution) and triple
quadrupole-based multiple reaction monitoring were comparable and achieved
detection limits of 0.030 and 0.015 ng/ml, respectively. As determined by
immunocapture and TOF-MS, drug-to-antibody ratio remained unchanged up to 3-weeks
postdose for an ADC containing engineered glutamine linkers, but declined from
four to three over 2 weeks in an ADC containing engineered cysteine linkers.
CONCLUSION: The use of high-resolution MS in ADC drug discovery confirms its
utility within the bioanalytical discipline.
PMID- 27487386
TI - A workflow for absolute quantitation of large therapeutic proteins in biological
samples at intact level using LC-HRMS.
AB - AIM: The commonly used LC-MS workflow to quantify protein therapeutics in
biological samples is 'bottom-up' approach. In this study, the aim is to
establish 'top-down' approach for absolute quantitation of therapeutic antibodies
or proteins of similar sizes in biological samples at intact level. MATERIALS &
METHODS: Using a recombinant human monoclonal antibody as the model molecule, we
present a workflow to measure large therapeutic proteins in plasma at intact
level based on deconvoluted high-resolution MS (HRMS) peaks. A novel MultiQuantTM
software function was developed to automatically deconvolute the peaks and
process the data. RESULTS & CONCLUSION: The workflow showed satisfying
performance. This is a proof of concept study demonstrating the feasibility of
bioanalysis of large therapeutic proteins at intact level using LC-HRMS.
PMID- 27487387
TI - Recent developments in software tools for high-throughput in vitro ADME support
with high-resolution MS.
AB - The last several years have seen the rapid adoption of the high-resolution MS
(HRMS) for bioanalytical support of high throughput in vitro ADME profiling. Many
capable software tools have been developed and refined to process quantitative
HRMS bioanalysis data for ADME samples with excellent performance. Additionally,
new software applications specifically designed for quan/qual soft spot
identification workflows using HRMS have greatly enhanced the quality and
efficiency of the structure elucidation process for high throughput metabolite ID
in early in vitro ADME profiling. Finally, novel approaches in data acquisition
and compression, as well as tools for transferring, archiving and retrieving HRMS
data, are being continuously refined to tackle the issue of large data file size
typical for HRMS analyses.
PMID- 27487388
TI - Structure-function analyses of microsomal triglyceride transfer protein missense
mutations in abetalipoproteinemia and hypobetalipoproteinemia subjects.
AB - We describe two new hypolipidemic patients with very low plasma triglyceride and
apolipoprotein B (apoB) levels with plasma lipid profiles similar to
abetalipoproteinemia (ABL) patients. In these patients, we identified two
previously uncharacterized missense mutations in the microsomal triglyceride
transfer protein (MTP) gene, R46G and D361Y, and studied their functional
effects. We also characterized three missense mutations (H297Q, D384A, and G661A)
reported earlier in a familial hypobetalipoproteinemia patient. R46G had no
effect on MTP expression or function and supported apoB secretion. H297Q, D384A,
and G661A mutants also supported apoB secretion similarly to WT MTP. Contrary to
these four missense mutations, D361Y was unable to support apoB secretion.
Functional analysis revealed that this mutant was unable to bind protein
disulfide isomerase (PDI) or transfer lipids. The negative charge at residue 361
was critical for MTP function as D361E was able to support apoB secretion and
transfer lipids. D361Y most likely disrupts the tightly packed middle alpha
helical region of MTP, mitigates PDI binding, abolishes lipid transfer activity,
and causes ABL. On the other hand, the hypolipidemia in the other two patients
was not due to MTP dysfunction. Thus, in this study of five missense mutations
spread throughout MTP's three structural domains found in three hypolipidemic
patients, we found that four of the mutations did not affect MTP function. Thus,
novel mutations that cause severe hypolipidemia probably exist in other genes in
these patients, and their recognition may identify novel proteins involved in the
synthesis and/or catabolism of plasma lipoproteins.
PMID- 27487389
TI - Women's knowledge and use of prenatal screening tests.
AB - AIMS AND OBJECTIVES: The aim of the study was to determine the rate of use of
prenatal screening tests and the factors affecting the decision to have a
prenatal screening test in pregnant women in Turkey. BACKGROUND: Prenatal genetic
screening as an optional service is commonly used to determine a level of risk
for genetic conditions in the foetus. DESIGN: A quantitative cross-sectional
survey. METHODS: Pregnant women (n = 274) who sought prenatal care from one
hospital in Turkey were recruited and asked to complete questionnaires that were
developed by the researchers. Descriptive and inferential statistics were used to
analyse the data. RESULTS: Almost half (44.2) % of the women were primiparas, and
the majority (97.8%) were in the third trimester of pregnancy. Only 36.1% of the
women reported that they had prenatal screening by either the double test or
triple test. Women had a low level of knowledge regarding prenatal screening: the
mean knowledge score was 3.43 +/- 3.21 of a possible score of 10. Having
consanguineous marriage, a history of spontaneous abortion, a child with genetic
disorder, multiparity or a longer marriage duration were positively correlated
with accepting a prenatal screening test. CONCLUSIONS: This study has provided
baseline data on the uptake and reasons for accepting or declining a prenatal
screening in a cohort of Turkish women. There is evidence to suggest that more
education is needed to improve knowledge and provide comprehensive nursing care
to promote informed consent in this context. RELEVANCE TO CLINICAL PRACTICE:
Perinatal nurses are ideally situated to inform pregnant women about prenatal
screening tests to improve access to healthcare services and to ensure informed
decisions are made by pregnant women and their partners.
PMID- 27487391
TI - Multimodal Spectroscopic Study of Amyloid Fibril Polymorphism.
AB - Amyloid fibrils are a large class of self-assembled protein aggregates that are
formed from unstructured peptides and unfolded proteins. The fibrils are
characterized by a universal beta-sheet core stabilized by hydrogen bonds, but
the molecular structure of the peptide subunits exposed on the fibril surface is
variable. Here we show that multimodal spectroscopy using a range of bulk- and
surface-sensitive techniques provides a powerful way to dissect variations in the
molecular structure of polymorphic amyloid fibrils. As a model system, we use
fibrils formed by the milk protein beta-lactoglobulin, whose morphology can be
tuned by varying the protein concentration during formation. We investigate the
differences in the molecular structure and composition between long, straight
fibrils versus short, wormlike fibrils. We show using mass spectrometry that the
peptide composition of the two fibril types is similar. The overall molecular
structure of the fibrils probed with various bulk-sensitive spectroscopic
techniques shows a dominant contribution of the beta-sheet core but no difference
in structure between straight and wormlike fibrils. However, when probing
specifically the surface of the fibrils with nanometer resolution using tip
enhanced Raman spectroscopy (TERS), we find that both fibril types exhibit a
heterogeneous surface structure with mainly unordered or alpha-helical structures
and that the surface of long, straight fibrils contains markedly more beta-sheet
structure than the surface of short, wormlike fibrils. This finding is consistent
with previous surface-specific vibrational sum-frequency generation (VSFG)
spectroscopic results ( VandenAkker et al. J. Am. Chem. Soc. , 2011 , 133 , 18030
- 18033 , DOI: 10.1021/ja206513r ). In conclusion, only advanced vibrational
spectroscopic techniques sensitive to surface structure such as TERS and VSFG are
able to reveal the difference in structure that underlies the distinct morphology
and rigidity of different amyloid fibril polymorphs that have been observed for a
large range of food and disease-related proteins.
PMID- 27487392
TI - More end resection is not merrier.
PMID- 27487390
TI - TBC1D20 mediates autophagy as a key regulator of autophagosome maturation.
AB - In humans, loss of TBC1D20 (TBC1 domain family, member 20) protein function
causes Warburg Micro syndrome 4 (WARBM4), an autosomal recessive disorder
characterized by congenital eye, brain, and genital abnormalities. TBC1D20
deficient mice exhibit ocular abnormalities and male infertility. TBC1D20 is a
ubiquitously expressed member of the family of GTPase-activating proteins (GAPs)
that increase the intrinsically slow GTP-hydrolysis rate of small RAB-GTPases
when bound to GTP. Biochemical studies have established TBC1D20 as a GAP for
RAB1B and RAB2A. However, the cellular role of TBC1D20 still remains elusive, and
there is little information about how the functional loss of TBC1D20 causes
clinical manifestations in WARBM4-affected children. Here we evaluate the role of
TBC1D20 in cells carrying a null mutant allele, as well as TBC1D20-deficient
mice, which display eye and testicular abnormalities. We demonstrate that
TBC1D20, via its RAB1B GAP function, is a key regulator of autophagosome
maturation, a process required for maintenance of autophagic flux and degradation
of autophagic cargo. Our results provide evidence that TBC1D20-mediated
autophagosome maturation maintains lens transparency by mediating the removal of
damaged proteins and organelles from lens fiber cells. Additionally, our results
show that in the testes TBC1D20-mediated maturation of autophagosomes is required
for autophagic flux, but is also required for the formation of acrosomes.
Furthermore TBC1D20-deficient mice, while not mimicking severe developmental
brain abnormalities identified in WARBM4 affected children, display disrupted
neuronal autophagic flux resulting in adult-onset motor dysfunction. In summary,
we show that TBC1D20 has an essential role in the maturation of autophagosomes
and a defect in TBC1D20 function results in eye, testicular, and neuronal
abnormalities in mice implicating disrupted autophagy as a mechanism that
contributes to WARBM4 pathogenesis.
PMID- 27487393
TI - A route to new cancer therapies: the FA pathway is essential in BRCA1- or BRCA2
deficient cells.
PMID- 27487394
TI - Catch me if you can: trapping scanning ribosomes in their footsteps.
PMID- 27487395
TI - Thermal Expansion Anomaly in TTB Ferroelectrics: The Interplay between Framework
Structure and Electric Polarization.
AB - Tetragonal tungsten bronze (TTB) makes up a large family of functional materials
with fascinating dielectric, piezoelectric, or ferroelectric properties.
Understanding the thermal expansion mechanisms associated with their physical
properties is important for their practical applications as well as theoretical
investigations. Fortunately, the appearance of anomalous thermal expansion in
functional materials offers a chance to capture the physics behind them. Herein,
we report an investigation of the thermal expansion anomalies in TTBs that are
related to ferroelectric transitions and summarize recent progress in this field.
The special role of Pb(2+) cation is elucidated. The interplay between the
thermal expansion anomaly, electric polarization, and framework structure
provides new insight into the structure-property relationships in functional
materials.
PMID- 27487396
TI - Sperm chromatin maturity and integrity correlated to zygote development in ICSI
program.
AB - This study aimed to evaluate sperm chromatin maturity and integrity of that
injected into good-quality oocytes in an in vitro fertilization-intra cytoplasmic
sperm injection (IVF-ICSI) program. A cut-off value of sperm chromatin maturity
and integrity was developed as a function of their correlation to the zygote
development, i.e., embryo formation and cleavage rate. The study assessed sperm
chromatin maturity using aniline blue (AB) staining, whereas toluidine blue (TB)
staining was used to assess sperm chromatin integrity. Ejaculates from 59
patients undergoing ICSI and 46 fertile normozoospermic donors for determination
of normal values of sperm chromatin status were used in this study. Embryo
formation and cleavage rates were observed for the period of 3 days after ICSI.
There was a significant difference in the percentage of sperm with mature
chromatin between ejaculate from ICSI patients and fertile donor (p=0.020); while
there was no significant difference in sperm chromatin integrity of both samples
(p=0.120). There was no significant correlation between sperm chromatin maturity
and either embryo formation or cleavage rate; as well as sperm chromatin
integrity to both parameters of zygote development (p>0.05). Furthermore, we
found that the cut-off value of sperm chromatin maturity and integrity of the
fertile normozoospermic ejaculates were 87.2% and 80.2%, respectively. Using the
cut-offs, we found that low sperm chromatin maturity at the level of <87%
correlated significantly with the cleavage rate of the zygote (p=0.022; r=0.371);
whereas poor sperm chromatin integrity at the level of <80% correlated with
embryo formation (p=0.048; r=0,485). In conclusion, this study showed that poor
maturity and integrity of sperm chromatin (AB<87% and TB<80%, respectively),
could affect zygote development following ICSI. ABBREVIATIONS: AB: aniline blue;
CMA3: chromomycin A3; ICSI: intra cytoplasmic sperm injection; IVF: in vitro
fertilization; PBS: phosphate buffer saline; SPSS: Statistical Package for Social
Science; TB: toluidine blue; WHO: World Health Organization.
PMID- 27487397
TI - Fecal Fermentation in Irritable Bowel Syndrome: Influence of Dietary Restriction
of Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols.
AB - BACKGROUND/AIMS: Dietary restriction of fermentable oligosaccharides,
disaccharides, monosaccharides and polyols (FODMAPs) may relieve symptoms in
patients with irritable bowel syndrome (IBS). We investigated whether this diet
alters microbial fermentation, a process that may be involved in IBS symptom
generation. METHODS: Patients with IBS were included consecutively to participate
in a 4-week FODMAP restricted diet. IBS symptoms were evaluated by using the IBS
severity scoring system (IBS-SSS). Short-chain fatty acids (SCFAs) were analyzed
in fecal samples before and after the dietary intervention, both at baseline and
after in vitro fermentation for 24 h. RESULTS: Sixty-three patients completed the
study. Following the dietary intervention, IBS-SSS scores improved significantly
(p < 0.0001). Total SCFA levels were reduced in fecal samples analyzed both at
baseline (p = 0.005) and after in vitro fermentation for 24 h (p = 0.013).
Following diet, baseline levels of acetic (p = 0.003) and n-butyric acids (p =
0.009) decreased, whereas 24 h levels of i-butyric (p = 0.003) and i-valeric
acids (p = 0.003) increased. Fecal SCFA levels and IBS symptom scores were not
correlated. CONCLUSION: Dietary FODMAP restriction markedly modulated fecal
fermentation in patients with IBS. Saccharolytic fermentation decreased, while
proteolytic fermentation increased, apparently independent of symptoms.
PMID- 27487398
TI - Leptospira Seroprevalence and Risk Factors in Health Centre Patients in Hoima
District, Western Uganda.
AB - BACKGROUND: The burden of human leptospirosis in Uganda is unknown. We estimated
the seroprevalence of Leptospira antibodies, probable acute/recent leptospirosis,
and risk factors for seropositivity in humans in rural Western Uganda.
METHODOLOGY AND PRINCIPAL FINDINGS: 359 non-pregnant adults visiting the Kikuube
and Kigorobya Health Centers were sequentially recruited during March and April
2014. A health history survey and serum were collected from consented
participants. Overall, 69% reported having fever in the past year, with 49%
reporting malaria, 14% malaria relapse, 6% typhoid fever, 3% brucellosis, and 0%
leptospirosis. We tested sera by microscopic agglutination test (MAT) against
eight Leptospira serovars representing seven serogroups. Leptospira
seroprevalence was 35% (126/359; 95%CI 30.2-40.3%) defined as MAT titer >= 1:100
for any serovar. The highest prevalence was against L. borgpetersenii Nigeria
(serogroup Pyrogenes) at 19.8% (71/359; 95%CI 15.9-24.4%). The prevalence of
probable recent leptospirosis (MAT titer >=1:800) was 1.9% (95%CI 0.9-4.2%) and
uniquely related to serovar Nigeria (serogroup Pyrogenes). Probable recent
leptospirosis was associated with having self-reported malaria within the past
year (p = 0.048). Higher risk activities included skinning cattle (n = 6) with
12.3 higher odds (95%CI 1.4-108.6; p = 0.024) of Leptospira seropositivity
compared with those who had not. Participants living in close proximity to
monkeys (n = 229) had 1.92 higher odds (95%CI 1.2-3.1; p = 0.009) of
seropositivity compared with participants without monkeys nearby.
CONCLUSIONS/SIGNIFICANCE: The 35% prevalence of Leptospira antibodies suggests
that exposure to leptospirosis is common in rural Uganda, in particular the
Nigeria serovar (Pyrogenes serogroup). Leptospirosis should be a diagnostic
consideration in febrile illness and "smear-negative malaria" in rural East
Africa.
PMID- 27487399
TI - Epidural spinal cavernous hemangioma and hybrid vascular subtype.
AB - AIM: To demonstrate less common pathologies of purely epidural spinal tumors that
should be considered when noted on MRI prior to surgery. To expand the
differential diagnosis of purely epidural spinal tumors and comment on their
surgical implications. MATERIAL AND METHODS: We report on two patients from our
institution with rare pathology. We also utilized PubMed to concisely review the
literature concerning purely epidural vascular lesions akin to the cavernous
hemangioma. RESULTS: We describe common clinical presentations, radiographic
findings, histopathologic characteristics and treatment algorithms relevant to
the rare pure spinal epidural cavernous hemangioma and a newly described compound
hemangioma subtype. CONCLUSION: Epidural spinal tumors are relatively common
entities, though lesions isolated to the epidural space without origination in
the vertebral body or as part of neurologic presentation of metastatic disease,
are much less common. Less common pathologies may be missed in the initial
differential diagnosis with treatment implications at surgery.
PMID- 27487400
TI - The adaptor protein p40phox as a positive regulator of the superoxide-producing
phagocyte oxidase.
PMID- 27487401
TI - Association of Lipid Fractions With Risks for Coronary Artery Disease and
Diabetes.
AB - IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C) is causally related to
coronary artery disease (CAD), but the relevance of high-density lipoprotein
cholesterol (HDL-C) and triglycerides (TGs) is uncertain. Lowering of LDL-C
levels by statin therapy modestly increases the risk of type 2 diabetes, but it
is unknown whether this effect is specific to statins. OBJECTIVE: To investigate
the associations of 3 routinely measured lipid fractions with CAD and diabetes
through mendelian randomization (MR) using conventional MR and making use of
newer approaches, such as multivariate MR and MR-Egger, that address the
pleiotropy of genetic instruments where relevant. DESIGN, SETTING, AND
PARTICIPANTS: Published data from genome-wide association studies were used to
construct genetic instruments and then applied to investigate associations
between lipid fractions and the risk of CAD and diabetes using MR approaches that
took into account pleiotropy of genetic instruments. The study was conducted from
March 12 to December 31, 2015. MAIN OUTCOMES AND MEASURES: Coronary artery
disease and diabetes. RESULTS: Genetic instruments composed of 130 single
nucleotide polymorphisms (SNPs) were used for LDL-C (explaining 7.9% of its
variance), 140 SNPs for HDL-C (6.6% of variance), and 140 SNPs for TGs (5.9% of
variance). A 1-SD genetically instrumented elevation in LDL-C levels (equivalent
to 38 mg/dL) and TG levels (equivalent to 89 mg/dL) was associated with higher
CAD risk; odds ratios (ORs) were 1.68 (95% CI, 1.51-1.87) for LDL-C and 1.28 (95%
CI, 1.13-1.45) for TGs. The corresponding OR for HDL-C (equivalent to a 16-mg/dL
increase) was 0.95 (95% CI, 0.85-1.06). All 3 lipid traits were associated with a
lower risk of type 2 diabetes. The ORs were 0.79 (95% CI, 0.71-0.88) for LDL-C
and 0.83 (95% CI, 0.76-0.90) for HDL-C per 1-SD elevation. For TG, the MR
estimates for diabetes were inconsistent, with MR-Egger giving an OR of 0.83
(95%CI, 0.72-0.95) per 1-SD elevation. CONCLUSIONS AND RELEVANCE: Routinely
measured lipid fractions exhibit contrasting associations with the risk of CAD
and diabetes. Increased LDL-C, HDL-C, and possibly TG levels are associated with
a lower risk of diabetes. This information will be relevant to the design of
clinical trials of lipid-modifying agents, which should carefully monitor
participants for dysglycemia and the incidence of diabetes.
PMID- 27487402
TI - Alkylation of Sulfonamides with Trichloroacetimidates under Thermal Conditions.
AB - An intermolecular alkylation of sulfonamides with trichloroacetimidates is
reported. This transformation does not require an exogenous acid, base, or
transition metal catalyst; instead the addition occurs in refluxing toluene
without additives. The sulfonamide alkylation partner appears to be only limited
by sterics, with unsubstituted sulfonamides providing better yields than more
encumbered N-alkyl sulfonamides. The trichloroacetimidate alkylating agent must
be a stable cation precursor for the substitution reaction to proceed under these
conditions.
PMID- 27487403
TI - Charge Transfer States in Dilute Donor-Acceptor Blend Organic Heterojunctions.
AB - We study the charge transfer (CT) states in small-molecule blend heterojunctions
comprising the nonpolar donor, tetraphenyldibenzoperiflanthene (DBP), and the
acceptor, C70, using electroluminescence and steady-state and time-resolved
photoluminescence spectroscopy along with density functional theory calculations.
We find that the CT exciton energy blue shifts as the C70 concentration in the
blend is either decreased or increased away from 50 vol %. At 20 K, the increase
in CT state lifetime is correlated with the increasing diameter of C70
nanocrystallites in the blends. A quantum confinement model is used to
quantitatively describe the dependence of both CT energy and lifetime on the C70
or DBP domain size. Two discrete CT emission peaks are observed for blends whose
C70 concentration is >65%, at which point C70 nanocrystallites with diameters >4
nm appear in high-resolution transmission electron micrographs. The presence of
two CT states is attributed to coexistence of crystalline C70 and amorphous
phases in the blends. Furthermore, analysis of CT dissociation efficiency versus
photon energy suggests that the >90% dissociation efficiency of delocalized CT2
states from the crystalline phase significantly contributes to surprisingly
efficient photogeneration in highly dilute (>80% C70) DBP/C70 heterojunctions.
PMID- 27487404
TI - An Electrocardiogram-Based Risk Equation for Incident Cardiovascular Disease From
the National Health and Nutrition Examination Survey.
AB - Importance: Electrocardiography (ECG) may detect subclinical cardiovascular
disease (CVD) in asymptomatic individuals, but its role in assessing adverse
events beyond traditional risk factors is not clear. Interval and vector data
that are commonly available on modern ECGs may offer independent prognostic
information that improves risk classification. Objectives: To derive and validate
a CVD risk equation based on ECG metrics and to determine its incremental benefit
in addition to the Framingham risk score (FRS). Design, Setting, and
Participants: This study included 3640 randomly selected community-based adults
aged 40 to 74 years without known CVD from the First National Health and
Nutrition Examination Survey (NHANES I) cohort (1971-1975) and 6329 from the
NHANES III cohort (1988-1994). Participants were sampled from across the United
States. A risk score to assess incident nonfatal and fatal CVD events was derived
based on computer-generated ECG data, including frontal P, R, and T axes; heart
rate; and PR, QRS, and QT intervals from NHANES I. The most prognostic variables,
along with age and sex, were incorporated into the NHANES ECG risk equation. The
equation was evaluated in the NHANES III cohort for an independent validation.
Follow-up in the NHANES III cohort was completed on December 31, 2006. Data for
this study were analyzed from August 11, 2015, to May 20, 2016. Main Outcomes and
Measures: The primary end point was CVD death. Secondary outcomes included 10
year ischemic heart disease and all-cause death. Results: The final study sample
included 9969 participants (4714 men [47.3%]; 5255 women [52.7%]; mean [SD] age,
55.3 [10.1] years) from both cohorts. Frontal T axis, heart rate, and heart rate
corrected QT interval were the most significant ECG factors in the NHANES I
cohort. In the validation cohort (NHANES III), the equation provided for
prognostic information for fatal CVD with a hazard ratio (HR) of 3.23 (95% CI,
2.82-3.72); the C statistic was 0.79 (95% CI, 0.76-0.81). When added to the FRS
in Cox proportional hazards regression models, the categorical (1%, 5%, and 10%
cutoffs) net reclassification improvement was 24%. When the FRS and ECG scores
were combined in a single model, the C statistic improved by 0.04 (95% CI, 0.02
0.06) to 0.80 (95% CI, 0.77-0.82). Similar improvements were noted when the ECG
score was added to the pooled cohort equation. When the equation for prognostic
information about ischemic heart disease and all-cause death was evaluated, the
results were similar. Conclusions and Relevance: An ECG risk score based on age,
sex, heart rate, frontal T axis, and QT interval assesses the risk for CVD and
compares favorably with the FRS alone in an independent cohort of asymptomatic
individuals. Although the ECG risk equation is low cost, further research is
needed to ascertain whether this additional step in risk stratification may
improve prevention efforts and reduce CVD events.
PMID- 27487405
TI - Antenatal corticosteroid treatment: factors other than lung maturation.
AB - Antenatal corticosteroid (CS) therapy improves both fetal lung mechanism and gas
exchange due to accelerated morphologic development of type one and two
pneumocytes. This therapy also enhances the production of surfactant binding
proteins and fetal lung antioxidant enzymes. In women with threatening preterm
delivery, a single course is advocated between 24 and 34 weeks' gestation with
either betamethasone (two doses of 12 mg 24 h apart) or dexamethasone (four doses
of 6 mg at 12-h intervals). Such treatment reduces the rate of respiratory
distress syndrome, comorbidity, and mortality in neonates in the first 48 h of
life. The optimal time interval between CS administration and delivery is
reported to be 1-7 days. Weekly repeat courses reduce the occurrences and
severity of respiratory diseases but are associated with reduce fetal growth.
Multiple courses should be avoided. However, a repeat course should be considered
in women at risk of preterm birth 7 or more days after an initial course in women
who remain at risk of preterm birth <34 weeks' gestation. CS may be harmful in
growth restricted fetuses associated with an absent or reversed end-diastolic UA
flow since they are at increased risk of acidosis and perinatal death. The
purpose of this publication is to update and highlight antenatal CS therapy.
PMID- 27487406
TI - The Effects of Oscillatory Biofield Therapy on Pain and Functional Limitations
Associated with Carpal Tunnel Syndrome: Randomized, Placebo-Controlled, Double
Blind Study.
AB - OBJECTIVES: Biofield treatments have been used for pain control in patients with
cancer and chronic pain. However, research on the effect of biofield treatment on
specific somatic disorders is lacking. This study intends to investigate the
effect of oscillating biofield therapy (OBFT) on symptoms of carpal tunnel
syndrome. DESIGN: Randomized, placebo-controlled, double-blind study.
PARTICIPANTS: Thirty patients with chronic carpal tunnel syndrome participated in
the study. INTERVENTION: Patients were randomly assigned to active or placebo
treatment groups. Those in the treatment group received six sessions of OBFT with
intention to treat during a period of 2 weeks. Patients in the placebo group had
the same number of treatment sessions with mock OBFT treatment. OUTCOME MEASURE:
The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; Symptom
Severity Scale (SSS); and Functional Status Scale (FSS) were used for outcome
assessment. RESULTS: Both clinically and statistically significant changes in
intensity of pain with activity (95% confidence interval [CI], 2.5-4.2; p =
0.000), night pain (p = 0.000, 95% CI, 3.2-5.7), DASH questionnaire (95% CI, 12.0
21.9; p = 0.000), SSS (95% CI, 0.64-1.15; p = 0.003), and FSS (95% CI, 0.41-0.97;
p = 0.029) were found between the treatment and placebo groups. Statistically
significant reduction in number of patients with positive results on the Phalen
test (87%; p = 0.000), Tinel sign (73%; p = 0.000), and hand paresthesia (80%; p
= 0.000) was noted in the treatment group. During 6-month follow-up, 86% of
patients in the treatment group remained pain free and had no functional
limitations. CONCLUSION: OBFT can be a viable and effective treatment for
improving symptoms and functional limitations associated with chronic carpal
tunnel syndrome.
PMID- 27487408
TI - Effects of Live and Educational Music Therapy on Working Alliance and Trust With
Patients on Detoxification Unit: A Four-Group Cluster-Randomized Trial.
AB - BACKGROUND: Lyric analysis is a commonly utilized music therapy intervention for
clients in substance abuse rehabilitation wherein participants interpret song
lyrics related to their clinical objectives. For these patients, working alliance
and trust in the therapist represent consequential factors that may influence
outcomes. However, there is a lack of randomized controlled music therapy studies
investigating working alliance and trust in the therapist within lyric analysis
interventions for patients with addictions. OBJECTIVE: The purpose of this study
was to quantitatively differentiate live versus recorded and educational versus
recreational music therapy interventions via measures of working alliance and
trust with patients on a detoxification unit. METHOD: Participants (N = 130) were
cluster randomized in a single-session posttest-only design to one of four
conditions: Live educational music therapy, recorded educational music therapy,
education without music, or recreational music therapy. Dependent measures
included working alliance and trust in the therapist. Educational music therapy
interventions were scripted lyric analyses. RESULTS: There was no statistically
significant between-group difference in any of the measures. Although not
significant, a greater number of patients and research participants attended live
educational music therapy sessions. CONCLUSIONS: Between-group descriptive data
were consistently similar but attendance trends may have implications for
engaging patients and billing. Implications for clinical practice, limitations of
the study, and suggestions for future research are provided.
PMID- 27487407
TI - Metrics for the Human Proteome Project 2016: Progress on Identifying and
Characterizing the Human Proteome, Including Post-Translational Modifications.
AB - The HUPO Human Proteome Project (HPP) has two overall goals: (1) stepwise
completion of the protein parts list-the draft human proteome including
confidently identifying and characterizing at least one protein product from each
protein-coding gene, with increasing emphasis on sequence variants, post
translational modifications (PTMs), and splice isoforms of those proteins; and
(2) making proteomics an integrated counterpart to genomics throughout the
biomedical and life sciences community. PeptideAtlas and GPMDB reanalyze all
major human mass spectrometry data sets available through ProteomeXchange with
standardized protocols and stringent quality filters; neXtProt curates and
integrates mass spectrometry and other findings to present the most up to date
authorative compendium of the human proteome. The HPP Guidelines for Mass
Spectrometry Data Interpretation version 2.1 were applied to manuscripts
submitted for this 2016 C-HPP-led special issue [ www.thehpp.org/guidelines ].
The Human Proteome presented as neXtProt version 2016-02 has 16,518 confident
protein identifications (Protein Existence [PE] Level 1), up from 13,664 at 2012
12, 15,646 at 2013-09, and 16,491 at 2014-10. There are 485 proteins that would
have been PE1 under the Guidelines v1.0 from 2012 but now have insufficient
evidence due to the agreed-upon more stringent Guidelines v2.0 to reduce false
positives. neXtProt and PeptideAtlas now both require two non-nested, uniquely
mapping (proteotypic) peptides of at least 9 aa in length. There are 2,949
missing proteins (PE2+3+4) as the baseline for submissions for this fourth annual
C-HPP special issue of Journal of Proteome Research. PeptideAtlas has 14,629
canonical (plus 1187 uncertain and 1755 redundant) entries. GPMDB has 16,190 EC4
entries, and the Human Protein Atlas has 10,475 entries with supportive evidence.
neXtProt, PeptideAtlas, and GPMDB are rich resources of information about post
translational modifications (PTMs), single amino acid variants (SAAVSs), and
splice isoforms. Meanwhile, the Biology- and Disease-driven (B/D)-HPP has created
comprehensive SRM resources, generated popular protein lists to guide targeted
proteomics assays for specific diseases, and launched an Early Career Researchers
initiative.
PMID- 27487409
TI - Toward Inexpensive Photocatalytic Hydrogen Evolution: A Nickel Sulfide Catalyst
Supported on a High-Stability Metal-Organic Framework.
AB - Few-atom clusters composed of nickel and sulfur have been successfully installed
into the Zr(IV)-based metal-organic framework (MOF) NU-1000 via ALD-like
chemistry (ALD = atomic layer deposition). X-ray photoelectron spectroscopy and
Raman spectroscopy are used to determine that primarily Ni(2+) and S(2-) sites
are deposited within the MOF. In a pH 7 buffered aqueous solution, the porous
catalyst is able to produce H2 gas at a rate of 3.1 mmol g(-1) h(-1) upon UV
irradiation, whereas no H2 is generated by irradiating bare NU-1000. Upon visible
light irradiation, little H2 generation was observed; however, with the addition
of an organic dye, rose bengal, NiS-AIM can catalyze the production of H2 at an
enhanced rate of 4.8 mmol g(-1) h(-1). These results indicate that ALD in MOFs
(AIM) can engender reactivity within high surface area supports for applications
in the solar fuels field.
PMID- 27487410
TI - Targeting an Aromatic Hotspot in Plasmodium falciparum 1-Deoxy-d-xylulose-5
phosphate Reductoisomerase with beta-Arylpropyl Analogues of Fosmidomycin.
AB - Blocking the 2-C-methyl-d-erythrithol-4-phosphate pathway for isoprenoid
biosynthesis offers new ways to inhibit the growth of Plasmodium spp.
Fosmidomycin [(3-(N-hydroxyformamido)propyl)phosphonic acid, 1] and its acetyl
homologue FR-900098 [(3-(N-hydroxyacetamido)propyl)phosphonic acid, 2] potently
inhibit 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in
this biosynthetic pathway. Arylpropyl substituents were introduced at the beta
position of the hydroxamate analogue of 2 to study changes in lipophilicity, as
well as electronic and steric properties. The potency of several new compounds on
the P. falciparum enzyme approaches that of 1 and 2. Activities against the
enzyme and parasite correlate well, supporting the mode of action. Seven X-ray
structures show that all of the new arylpropyl substituents displace a key
tryptophan residue of the active-site flap, which had made favorable interactions
with 1 and 2. Plasticity of the flap allows substituents to be accommodated in
many ways; in most cases, the flap is largely disordered. Compounds can be
separated into two classes based on whether the substituent on the aromatic ring
is at the meta or para position. Generally, meta-substituted compounds are better
inhibitors, and in both classes, smaller size is linked to better potency.
PMID- 27487411
TI - Spinal Cord Infarction in Clinical Neurology: A Review of Characteristics and
Long-Term Prognosis in Comparison to Cerebral Infarction.
AB - Spinal cord stroke is rare accounting for 0.3-1% of all strokes and is classified
into upper (cervical) and lower (thoracolumbar) strokes. Patients present with
severe deficits but later often show good functional improvement. On admission,
younger age, male gender, hypertension, diabetes mellitus and elevated blood
glucose indicate more severe spinal cord strokes. Treatment of these risk factors
is essential in the acute phase. Biphasic spinal cord strokes are seen in one
fifth of the patients. These present with acute or transient sensory spinal cord
deficits often preceded by radiating pain between the shoulders, and should be
considered and treated as imminent spinal cord strokes. Spinal cord infarction
patients are younger and more often women compared to cerebral infarction
patients. Traditional cerebrovascular risk factors are less relevant in spinal
cord infarction. Spinal cord infarction patients are more likely to be discharged
home and show better improvement after initial treatment compared to cerebral
infarction patients. On long-term follow-up, spinal cord infarction patients have
lower mortality and higher emotional well-being scores than cerebral infarction
patients. Despite more chronic pain, the frequency of re-employment is higher
among spinal cord infarction patients compared to cerebral infarction patients
who are more often afflicted with cognitive function deficits.
PMID- 27487412
TI - Strongly Coupled Nanotube Electromechanical Resonators.
AB - Coupling an electromechanical resonator with carbon-nanotube quantum dots is a
significant method to control both the electronic charge and the spin quantum
states. By exploiting a novel microtransfer technique, we fabricate two separate
strongly coupled and electrically tunable mechanical resonators for the first
time. The frequency of the two resonators can be individually tuned by the bottom
gates, and in each resonator, the electron transport through the quantum dot can
be strongly affected by the phonon mode and vice versa. Furthermore, the
conductance of either resonator can be nonlocally modulated by the other
resonator through phonon-phonon interaction between the two resonators. Strong
coupling is observed between the phonon modes of the two resonators, where the
coupling strength larger than 200 kHz can be reached. This strongly coupled
nanotube electromechanical resonator array provides an experimental platform for
future studies of the coherent electron-phonon interaction, the phonon-mediated
long-distance electron interaction, and entanglement state generation.
PMID- 27487413
TI - Failure of Density Functional Dispersion Correction in Metallic Systems and Its
Possible Solution Using a Modified Many-Body Dispersion Correction.
AB - Previous density functional dispersion corrections to density functional theory
lead to an unphysical description of metallic systems, as exemplified by alkali
and alkaline earth compounds. We demonstrate that it is possible to remedy this
limitation by including screening effects into the form of interacting smeared
out dipoles in the many-body expansion of the interaction. Our new approach,
called the coupled fluctuating smeared dipole model, describes equally well
noncovalent systems, such as molecular pairs and crystals, and metallic systems.
PMID- 27487414
TI - The role of Rho kinase (Rock) in re-epithelialization of adult zebrafish skin
wounds.
AB - Complete re-epithelialization of full-thickness skin wounds in adult mammals
takes days to complete and relies on numerous signaling cues and multiple
overlapping cellular processes that take place both within the epidermis itself
and in other participating tissues. We have previously shown that re
epithelialization of full-thickness skin wounds of adult zebrafish, however, is
extremely rapid and largely independent of the other processes of wound healing
allowing for the dissection of specific processes that occur in, or have a direct
effect on, re-epithelializing keratinocytes. Recently, we have shown that, in
addition to lamellipodial crawling at the leading edge, re-epithelialization of
zebrafish partial- and full-thickness wounds requires long-range epithelial
rearrangements including radial intercalations, flattening and directed
elongation and that each of these processes involves Rho kinase (Rock) signaling.
Our studies demonstrate how these coordinated signaling events allow for the
rapid collective cell migration observed in adult zebrafish wound healing. Here
we discuss the particular contribution of Rock to each of these processes.
PMID- 27487415
TI - Rotavirus epidemiology and surveillance before vaccine introduction in Argentina,
2012-2014.
AB - Group A Rotavirus has been widely described as one of the most important
infantile diarrheal pathogens worldwide. In Argentina, it is responsible for over
200,000 acute diarrhea cases and from 30 to 50 deaths annually in children under
5 years. The aim of this study is to analyze frequency, seasonality, age group
distribution, and circulating genotypes based on data notified in the 2012-2014
period and in turn to assess the pre-vaccine scenario, considering that rotavirus
vaccine was introduced in 2015. Data were taken from the Viral Diarrhea
Notification module of the Argentine SNVS-SIVILA surveillance tool. Analyses of
circulating genotypes were performed on rotavirus-positive stool specimens by
conventional binary characterization of the outermost capsid genes. Overall data
showed rotavirus detection in about 25% of samples tested, and higher rates in
children under 2 years old were observed. Rotavirus positive cases were
distributed according to a typical winter seasonal pattern. A heterogeneous
regional pattern of prevalence was also observed, with higher rates detected in
the North region. Genotype co-circulation and annual fluctuation were observed.
In general, G1P[8], G2P[4], G3P[8], and G12P[8] were the most frequently detected
genotypes. This study represents the last survey taken of a population considered
to be naive. J. Med. Virol. 89:423-428, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27487417
TI - Retraction.
PMID- 27487416
TI - Behavioral consequences of exposure to a high fat diet during the post-weaning
period in rats.
AB - We explored the impact of exposure to an obesogenic diet (High Fat-High Sucrose;
HFS) during the post-weaning period on sweet preference and behaviors linked to
reward and anxiety. All rats were fed chow. In addition a HFS-transient group had
access to this diet for 10days from post-natal (PN) day 22 and a HFS-continuous
group continued access until adult. Behavioral tests were conducted immediately
after PN 32 (adolescence) or after PN 60 (adult) and included: the condition
place preference (CPP) test for chocolate, sugar and saccharin preference
(anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor
response to quinpirole in the open field. Behavior was unaltered in adult rats in
the HFS-transient group, suggesting that a short exposure to this obesogenic food
does not induce long-term effects in food preferences, reward perception and
value of palatable food, anxiety or locomotor activity. Nevertheless, rats that
continued to have access to HFS ate less chocolate during CPP training and
consumed less saccharin and sucrose when tested in adolescence, effects that were
attenuated when these rats became adult. Moreover, behavioral effects linked to
transient HFS exposure in adolescence were not sustained if the rats did not
remain on that diet until adult. Collectively our data demonstrate that exposure
to fat and sucrose in adolescence can induce immediate reward hypofunction after
only 10days on the diet. Moreover, this effect is attenuated when the diet is
extended until the adult period, and completely reversed when the HFS diet is
removed.
PMID- 27487418
TI - Oxygen uptake, respiratory exchange ratio, or total distance: a comparison of
methods to equalize exercise volume in Wistar rats.
AB - This study compared strategies to equalize the volume of aerobic exercise
performed with different intensities by Wistar rats, based on the distance
covered during exercise bouts and energy expenditure (EE, isocaloric sessions)
obtained from oxygen uptake (VO2) or respiratory exchange ratio (RER). Thirty
three male rats (270.5+/-12.8 g) underwent maximal exercise tests to determine
VO2 reserve (VO2R), being randomly assigned to three groups: moderate-intensity
continuous exercise at speed corresponding to 50% VO2R (MIC; n=11); high
intensity continuous exercise at 80% VO2R (HIC; n=11); and high-intensity
intermittent exercise (HII; n=11) at 60% VO2R (3 min) and 80% VO2R (4 min).
Exercise duration was calculated individually to elicit EE of 5 kcal in each
session. No difference between groups was found for total running distance (MIC:
801+/-46, HIC: 734+/-42, HII: 885+/-64 m; P=0.13). Total EE measured by RER was
systematically underestimated compared to values obtained from VO2 (HII: 4.5% and
MIC: 6.2%, P<0.05). Total EE (calculated from VO2), and duration of HIC bouts
(2.8 kcal and 30.8+/-2.2 min) were lower (P<0.0001) than in MIC (4.9 kcal and
64.7+/-1.8 min) and HII (4.7 kcal and 46.9+/-2.2 min). Predicted and actual
values of total VO2, total EE, and duration of isocaloric sessions were similar
in MIC and HII (P>0.05), which were both higher than in HIC (P<0.0001). In
conclusion, the time to achieve a given EE in exercise bouts with different
intensities did not correspond to the total distance. Therefore, the volume of
aerobic exercise in protocols involving Wistar rats should be equalized using EE
rather than total covered distance.
PMID- 27487419
TI - Renin-angiotensin system blockers regulate the metabolism of isolated fat cells
in vitro.
AB - Due to the presence of the renin-angiotensin system (RAS) in tissues and its
specific influence on white adipose tissue, fat cells are possible targets of
pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the
present study, we investigated the effects of different RAS blockers on fat cell
metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy
substrates. Isolated primary adipocytes were incubated with different RAS
blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis,
lipogenesis and glucose oxidation capacities were determined in dose-response
assays to a beta-adrenergic agonist and to insulin. Although no change was found
in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose
oxidation in a different way. While captopril decreased insulin-stimulated
lipogenesis (-19% of maximal response and -60% of insulin responsiveness) due to
reduced glucose derived glycerol synthesis (-19% of maximal response and 64% of
insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation
(+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our
experiments demonstrate that RAS blockers can differentially induce metabolic
alterations in adipocyte metabolism, characterized by a reduction in lipogenic
responsiveness or an increase in glucose oxidation. The impact of RAS blockers on
adipocyte metabolism may have beneficial implications on metabolic disorders
during their therapeutic use in hypertensive patients.
PMID- 27487420
TI - Water-Mediated Interactions between Hydrophilic and Hydrophobic Surfaces.
AB - All surfaces in water experience at short separations hydration repulsion or
hydrophobic attraction, depending on the surface polarity. These interactions
dominate the more long-ranged electrostatic and van der Waals interactions and
are ubiquitous in biological and colloidal systems. Despite their importance in
all scenarios where the surface separation is in the nanometer range, the origin
of these hydration interactions is still unclear. Using atomistic solvent
explicit molecular dynamics simulations, we analyze the interaction free energies
of charge-neutral model surfaces with different elastic and water-binding
properties. The surface polarity is shown to be the most important parameter that
not only determines the hydration properties and thereby the water contact angle
of a single surface but also the surface-surface interaction and whether two
surfaces attract or repel. Elastic properties of the surfaces are less important.
On the basis of surface contact angles and surface-surface binding affinities, we
construct a universal interaction diagram featuring three different interaction
regimes-hydration repulsion, cavitation-induced attraction-and for intermediate
surface polarities-dry adhesion. On the basis of scaling arguments and
perturbation theory, we establish simple combination rules that predict the
interaction behavior for combinations of dissimilar surfaces.
PMID- 27487421
TI - Polycystic Ovary Syndrome and Obsessive-Compulsive Disorder: Interactions and
Psychopharmacological Considerations.
PMID- 27487422
TI - Direct and Indirect Measurements and Modeling of Methane Emissions in
Indianapolis, Indiana.
AB - This paper describes process-based estimation of CH4 emissions from sources in
Indianapolis, IN and compares these with atmospheric inferences of whole city
emissions. Emissions from the natural gas distribution system were estimated from
measurements at metering and regulating stations and from pipeline leaks. Tracer
methods and inverse plume modeling were used to estimate emissions from the major
landfill and wastewater treatment plant. These direct source measurements
informed the compilation of a methane emission inventory for the city equal to 29
Gg/yr (5% to 95% confidence limits, 15 to 54 Gg/yr). Emission estimates for the
whole city based on an aircraft mass balance method and from inverse modeling of
CH4 tower observations were 41 +/- 12 Gg/yr and 81 +/- 11 Gg/yr, respectively.
Footprint modeling using 11 days of ethane/methane tower data indicated that
landfills, wastewater treatment, wetlands, and other biological sources
contribute 48% while natural gas usage and other fossil fuel sources contribute
52% of the city total. With the biogenic CH4 emissions omitted, the top-down
estimates are 3.5-6.9 times the nonbiogenic city inventory. Mobile mapping of CH4
concentrations showed low level enhancement of CH4 throughout the city reflecting
diffuse natural gas leakage and downstream usage as possible sources for the
missing residual in the inventory.
PMID- 27487423
TI - Bona Fide Psychotherapy Models Are Equally Effective for Major Depressive
Disorder: Future Research Directions.
PMID- 27487424
TI - Nightmares in cardiology: Sudden cardiac death in a patient with apparently
healthy heart and "benign" outflow tract extrasystoles.
PMID- 27487425
TI - Viscosupplementation in Knee Osteoarthritis: Evidence Revisited.
AB - The body of evidence surrounding the use of viscosupplementation in knee
osteoarthritis is extensive and fraught with heterogeneous trials with
conflicting conclusions. Attempts to aggregate the evidence through systematic
reviews, meta-analyses, and guidelines have also resulted in unclear, discordant
recommendations. Closer examination reveals that the evidence around
viscosupplementation favors clinically important reductions in pain among higher
molecular-weight and cross-linked formulations and is a safe option in patients
with knee osteoarthritis. Further large trials assessing the use of
viscosupplementation across various formulations in knee osteoarthritis may
confirm subgroup findings from meta-analyses; however, immediate focus on
improved knowledge translation is required to ensure evidence-based approaches to
the treatment of knee osteoarthritis.
PMID- 27487426
TI - Arthroscopic Management of the Stiff Shoulder.
AB - Shoulder stiffness affects a diverse population of patients suffering a decrease
in function and shoulder pain. Arthroscopic management of this debilitating
spectrum of pathology is a safe and effective course of action in cases
recalcitrant to nonoperative therapy. Arthroscopic management of the stiff
shoulder has been reported to be effective in the treatment of stiffness due to
adhesive capsulitis, birth palsy, stiffness in the setting of rotator cuff tears,
and osteoarthritis in the posttraumatic patient, in the postoperative patient,
and in the throwing athlete. Arthroscopic management is most effective in
treating the stiff shoulder in the setting of adhesive capsulitis recalcitrant to
nonoperative therapy or posttraumatic stiffness. Results are more guarded in the
treatment of postoperative stiffness. Excessive force and trauma to the shoulder,
including fracture of the humerus, can be avoided with a 360[degrees] capsular
release for shoulder stiffness rather than manipulation under anesthesia.
PMID- 27487427
TI - Posterior Tibial Slope: Effect on, and Interaction with, Knee Kinematics.
AB - Posterior tibial slope should be measured on a long lateral or an expanded
lateral radiograph. Posterior tibial slope decreases the quadriceps force needed
to exert knee extension moment. Posterior tibial slope parallel to natural tibial
slope minimizes tibial component subsidence. Posterior tibial slope should be
increased rather than releasing the posterior cruciate ligament (PCL) to restore
normal kinematics in a knee that is tight in flexion. Larger tibial slope widens
the flexion gap in posterior stabilized total knee replacement.
PMID- 27487428
TI - Scapholunate Ligament Reconstruction: A Critical Analysis Review.
AB - Scapholunate reconstruction procedures are best stratified according to
preoperative stages of dissociative instability, injury chronicity, and
arthrosis. In general, procedures aimed at correcting scapholunate instability
focus on reestablishing ligament continuity in order to normalize carpal
biomechanics; however, many existing interventions have shown differential
success when performed on patients with varying stages of instability and degrees
of carpal malalignment. The Mayo dorsal intercarpal ligament capsulodesis has
proven most effective for preserving range of motion, whereas the Blatt
capsulodesis has been associated with substantial improvements in terms of the
postoperative pain rating and perceived functional capacity.
PMID- 27487429
TI - Challenging the Conventional Standard for Thoracic Spine Range of Motion: A
Systematic Review.
AB - BACKGROUND: Segmental motion is a fundamental characteristic of the thoracic
spine; however, studies of segmental ranges of motion have not been summarized or
analyzed. The purpose of the present study was to present a summary of the
literature on intact cadaveric thoracic spine segmental range of motion in each
anatomical plane. METHODS: A systematic MEDLINE search was performed with use of
the terms "thoracic spine," "motion," and "cadaver." Reports that included data
on the range of motion of intact thoracic human cadaveric spines were included.
Independent variables included experimental details (e.g., specimen age), type of
loading (e.g., pure moments), and applied moment. Dependent variables included
the ranges of motion in flexion-extension, lateral bending, and axial rotation.
RESULTS: Thirty-three unique articles were identified and included. Twenty-three
applied pure moments to thoracic spine specimens, with applied moments ranging
from 1.5 to 8 Nm. Estimated segmental range of motion pooled means ranged from
1.9 degrees to 3.8 degrees in flexion-extension, from 2.1 degrees to 4.4
degrees in lateral bending, and from 2.4 degrees to 5.2 degrees in axial
rotation. The sums of the range of motion pooled means (T1 to T12) were 28
degrees in flexion-extension, 36 degrees in lateral bending, and 45 degrees in
axial rotation. CONCLUSIONS: The pooled ranges of motion were similar to reported
in vivo motions but were considerably smaller in magnitude than the frequently
referenced values reported prior to the widespread use of biomechanical testing
standards. Improved reporting of biomechanical testing methods, as well as
specimen health, may be beneficial for improving on these estimations of
segmental cadaveric thoracic spine range of motion.
PMID- 27487430
TI - The Present and Future of Genomics in Adult Reconstructive Orthopaedic Surgery.
AB - As of 2015, members of the "baby boomer generation" comprise 75 million people in
the growing United States population. Many of these individuals will be facing
the need for total hip or knee replacement. Currently, the age of onset of
osteoarthritis continues to decrease and the need for total joint replacements
continues to increase. In current practice, nearly all patients undergoing joint
replacement receive similar preoperative, intraoperative, and postoperative
management strategies. However, wide variability in outcomes and satisfaction
with total joint replacement still remain. The key to understanding the cause for
such varied outcomes may lie in our understanding of the genetic basis of
degenerative joint disease. The future of "orthogenomic" research should be
centered on clinical application focusing on early preoperative identification of
at-risk patients. The goal is to establish twenty-first-century patient-specific
strategies for optimizing results and expectations after adult reconstructive
surgery.
PMID- 27487431
TI - Gastrointestinal stability, physicochemical characterization and oral
bioavailability of chitosan or its derivative-modified solid lipid nanoparticles
loading docetaxel.
AB - OBJECTIVE: The purpose of this study was to prepare the positively charged
chitosan (CS)- or hydroxypropyl trimethyl ammonium chloride chitosan (HACC)
modified solid lipid nanoparticles (SLNs) loading docetaxel (DTX), and to
evaluate their properties in vitro and in vivo. METHODS: The DTX-loaded SLNs (DTX
SLNs) were prepared through an emulsion solvent evaporation method and further
modified with CS or HACC (CS-DTX-SLNs or HACC-DTX-SLNs) via noncovalent
interactions. The gastrointestinal (GI) stability, dissolution rate,
physicochemical properties and cytotoxicities of SLNs were investigated. In
addition, the GI mucosa irritation and oral bioavailability of SLNs were also
evaluated in rats. RESULTS: The HACC-DTX-SLNs were highly stable in simulated
gastric and intestinal fluids (SGF and SIF). By contrast, the CS-DTX-SLNs were
less stable in SIF than in SGF. The drug dissolution remarkably increased when
DTX was incorporated into the SLNs, which may be attributed to the change in the
crystallinity of DTX and some molecular interactions that occurred between DTX
and the carriers. The SLNs showed low toxicity in Caco-2 cells and no GI mucosa
irritations were observed in rats. A 2.45-fold increase in the area under the
curve of DTX was found in the HACC-DTX-SLN group compared with the DTX group
after the modified SLNs were orally administered to rats. However, the oral
absorption of DTX-SLN or CS-DTX-SLN group showed no significant difference
compared with that of DTX group. CONCLUSIONS: The positively charged HACC-DTX
SLNs with a stable particle size could provide the enhanced oral bioavailability
of DTX in rats.
PMID- 27487432
TI - Change in Driving Performance following Arthroscopic Shoulder Surgery.
AB - The current study aimed to measure perioperative changes in driving performance
following arthroscopic shoulder surgery using a validated driving simulator.21
patients who underwent arthroscopic surgery for rotator cuff or labral pathology
were tested on a driving simulator preoperatively, and 6 and 12 weeks
postoperatively. An additional 21 subjects were tested to establish driving data
in a control cohort. The number of collisions, centerline crossings, and off-road
excursions were recorded for each trial. VAS and SPADI scores were obtained at
each visit.The mean number of collisions in the study group significantly
increased from 2.05 preoperatively to 3.75 at 6 weeks (p<0.001), and
significantly decreased to 1.95 at 12 weeks (p<0.001). Centerline crossings and
off-road excursions did not significantly change from preoperative through 12
weeks, although centerline crossings were statistically different from the
controls at each time point (p<0.001). Surgery on the dominant driving arm
resulted in greater collisions at 6 weeks than surgery on the non-dominant
driving arm (p<0.001).Preliminary data shows that driving performance is impaired
for at least 6 weeks postoperatively, with a return to normal driving by 12
weeks. Driving is more profoundly affected in conditions that require avoiding a
collision and when the dominant driving arm is involved.
PMID- 27487433
TI - Effects of nitrogen plasma treatment on the surface characteristics of olive
stone-based activated carbon.
AB - Nitrogen plasma treatment (NPT) of activated carbon (AC) at different conditions
was carried out to introduce nitrogen-containing groups onto olive stone
activated carbon (OSAC) surfaces. Textural characteristics of raw and irradiated
samples were analyzed by N2 and CO2 adsorption. Surface chemical functional
groups were analyzed by X-ray photoelectron spectrometry (XPS) and Fourier
Transformed Infrared spectroscopy. The results showed that after NPT, the surface
textural properties of irradiated OSAC were slightly damaged, and a gradual
decrease in surface area and pore volume was observed during the irradiation. XPS
revealed that NPT could change the distribution of oxygen functional groups on
the OSAC surface and there were more nitrogen atoms incorporated into the
aromatic ring. A tentative explanation for the modification process is proposed.
Phenol adsorption was enhanced from 110 mg/g for untreated AC to 635 mg/g for 30
min plasma-treated OSAC.
PMID- 27487434
TI - The impact of single and shared rooms on family-centred care in children's
hospitals.
AB - AIMS AND OBJECTIVES: To explore whether and how spatial aspects of children's
hospital wards (single and shared rooms) impact upon family-centred care.
BACKGROUND: Family-centred care has been widely adopted in paediatric hospitals
internationally. Recent hospital building programmes in many countries have
prioritised the provision of single rooms over shared rooms. Limited attention
has, however, been paid to the potential impact of spatial aspects of paediatric
wards on family-centred care. DESIGN: Qualitative, ethnographic. METHODS: Phase
1; observation within four wards of a specialist children's hospital. Phase 2;
interviews with 17 children aged 5-16 years and 60 parents/carers. Sixty nursing
and support staff also took part in interviews and focus group discussions. All
data were subjected to thematic analysis. RESULTS: Two themes emerged from the
data analysis: 'role expectations' and 'family-nurse interactions'. The latter
theme comprised three subthemes: 'family support needs', 'monitoring children's
well-being' and 'survey-assess-interact within spatial contexts'. CONCLUSION:
Spatial configurations within hospital wards significantly impacted upon the
relationships and interactions between children, parents and nurses, which played
out differently in single and shared rooms. Increasing the provision of single
rooms within wards is therefore likely to directly affect how family-centred care
manifests in practice. RELEVANCE TO CLINICAL PRACTICE: Nurses need to be
sensitive to the impact of spatial characteristics, and particularly of single
and shared rooms, on families' experiences of children's hospital wards. Nurses'
contribution to and experience of family-centred care can be expected to change
significantly when spatial characteristics of wards change and, as is currently
the vogue, hospitals maximise the provision of single rather than shared rooms.
PMID- 27487435
TI - Factors contributing to the low physical activity level for Hong Kong Chinese
children hospitalised with cancer: an exploratory study.
AB - AIMS AND OBJECTIVES: To explore the factors contributing to the low physical
activity level for Hong Kong Chinese children hospitalised with cancer.
BACKGROUND: Notwithstanding the fact that regular physical activity can
ameliorate cancer-related fatigue and other adverse effect of cancer treatment on
children's physical and psychological well-being, physical inactivity is a common
problem among children undergoing cancer treatment. Understanding the factors
that affect their physical activity level is an important step towards planning
and evaluating an appropriate intervention that promotes the adoption and
maintenance of regular physical activity. DESIGN: A phenomenological design was
used in this qualitative study. METHODS: A purposive sample of 25 children with
cancer was recruited in a paediatric oncology unit of an acute care public
hospital in Hong Kong. They were asked to participate in a semistructured
interview by their bedside lasting about 30 minutes. All the interviews were tape
recorded and immediately transcribed. Content analysis was used to analyse the
qualitative data. RESULTS: The findings revealed that the patients' physical
condition, misunderstanding about physical activity by children, parents and
healthcare professionals, emotional disturbances and social influences are four
important factors impeding children from engaging in regular physical activity
during cancer treatment. CONCLUSION: This study addresses a gap in the literature
by identifying the factors that negatively influence the physical activity levels
of Hong Kong Chinese children hospitalised with cancer. RELEVANCE TO CLINICAL
PRACTICE: Understanding these factors, nurses can explore interventions that
target on correcting the misunderstanding and providing relevant information
about the importance of physical activity, eventually promoting the adoption and
maintenance of regular physical activity and enhancing the quality of life.
PMID- 27487436
TI - Enhanced surveillance of Clostridium difficile infection occurring outside
hospital, England, 2011 to 2013.
AB - There are limited national epidemiological data for community-associated (CA)
Clostridium difficile infections (CDIs). Between March 2011 and March 2013,
laboratories in England submitted to the Clostridium difficile Ribotyping Network
(CDRN) up to 10 diarrhoeal faecal samples from successive patients with CA-CDI,
defined here as C. difficile toxin-positive diarrhoea commencing outside hospital
(or less than 48 hours after hospital admission), including those cases
associated with community-based residential care, with no discharge from hospital
within the previous 12 weeks. Patient demographics and C. difficile PCR ribotypes
were compared for CA-CDIs in our study and presumed healthcare-associated (HA)
CDIs via CDRN. Ribotype diversity indices, ranking and relative prevalences were
very similar in CA- vs HA-CDIs, although ribotypes 002 (p <= 0.0001),020 (p =
0.009) and 056 (p < 0.0001) predominated in CA-CDIs; ribotype 027 (p = 0.01)
predominated in HA-CDIs. Epidemic ribotypes 027 and 078 predominated in
institutional residents with CDI (including care/nursing homes) compared with
people with CDI living at home. Ribotype diversity decreased with increasing age
in HA-CDIs, but not in CA-CDIs. Ribotype 078 CA-CDIs were significantly more
common in elderly people (3.4% (6/174) vs 8.7% (45/519) in those aged < 65 and >=
65 years, respectively; p = 0.019). No antibiotics were prescribed in the
previous four weeks in about twofold more CA-CDI vs HAs (38.6% (129/334) vs 20.3%
(1,226/6,028); p < 0.0001). We found very similar ribotype distributions in CA-
and HA-CDIs, although a few ribotypes significantly predominated in one setting.
These national data emphasise the close interplay between, and likely common
reservoirs for, CDIs, particularly when epidemic strains are not dominant.
PMID- 27487437
TI - Qigong Yi Jinjing Promotes Pulmonary Function, Physical Activity, Quality of Life
and Emotion Regulation Self-Efficacy in Patients with Chronic Obstructive
Pulmonary Disease: A Pilot Study.
AB - PURPOSE: The purpose of this pilot study was to examine the effect of a Chinese
traditional exercise program, Qigong Yi Jinjing (QYJJ), on patients with chronic
obstructive pulmonary disease (COPD). METHODS: One hundred and thirty eligible
COPD patients were randomly divided into three groups: the QYJJ group (n = 42),
the self-management exercise group (n = 43), and the control group (n = 45). Data
were collected and analyzed at baseline and again at one, three, and six months.
A pulmonary rehabilitation index, consisting of pulmonary function, six-minute
walk test, Regulatory Emotion Self-Efficacy questionnaire, and exercise of the
COPD Assessment Test widely used to evaluate health-related quality of life
(HRQL) in participants with COPD, was measured. RESULTS: Compared with the other
groups, participants in QYJJ group had significantly better lung function (forced
expiratory volume in one second: F = 8.96, p = 0.000; forced expiratory volume in
one second/forced vital capacity: F = 11.55, p = 0.000; the percentage of forced
expiratory volume in one second in prediction: F = 24.27, p = 0.000); walked a
longer distance (F = 152.52, p = 0.000), and had more satisfactory HRQL (F =
14.08, p = 0.000). QYJJ training also contributed to improving the ability of
emotion regulation (F = 36.56, p = 0.000). There were significant positive
changes in expressing positive affect (F = 56.25, p = 0.000) and managing
despondency/distress (F = 21.58, p = 0.000), apart from the ability to regulate
anger/irritation (F = 1.20, p = 0.305). The longer QYJJ is practiced, the more
effective the influence is on the pulmonary rehabilitation-related index
measures. CONCLUSIONS: These results indicate that QYJJ exercise produced
positive effects on pulmonary function, physical activity, emotion regulation
self-efficiency (modulating the expression of despondency or distress and
experiencing and expressing positive affect), and HRQL in patients with COPD.
PMID- 27487438
TI - Two isoforms of Serpent containing either one or two GATA zinc fingers have
different roles in Drosophila haematopoiesis.
PMID- 27487439
TI - [Violence against women in transnational communities in San Luis Potosi, Mexico:
a public health problem].
AB - Violence against women is a worldwide problem due to its impact on quality of
life for those living under the complicity of a patriarchal culture and a state
that makes such violence invisible. This article aims to give visibility to the
contexts of violence affecting female "partners of migrants" in their places of
origin, problematizing how such violence assaults their physical and mental
health. This was a qualitative study with an interpretative anthropological
focus, drawing on a sample of 21 women from rural and urban areas in San Luis
Potosi, Mexico. Interviews were based on daily life history and discourse
analysis. According to the results, women experience more violence when their
spouses migrate, new forms of violence are committed against them, and the
violence occurs in both the household and the community. Violence against women
is a public health problem that should be treated through a framework that is
sensitive to the social and cultural dynamics characterizing the contexts in
which health programs are implemented.
PMID- 27487440
TI - [Perception, knowledge, and use of generic drugs in southern Brazil: what changed
from 2002 to 2012?].
AB - This study compared the perception, knowledge, and use of generic drugs by adults
in Pelotas, Rio Grande do Sul State, Brazil, using two cross-sectional population
based studies from 2002 and 2012. Study outcomes were: (a) prevalence of use of
generics; (b) generics as a proportion of all medication; (c) users' perceptions
of prices and quality; (d) users' knowledge of generics; and (e) strategies for
acquisition of medicines. Prevalence of generics use increased from 3.6% (95%CI:
3.0-4.3) to 26.1% (95%CI: 24.5-27.7) in the 10-year period. Perceptions of prices
and quality of generics remained stable, identification of characteristics that
distinguish generics from other drugs improved (p < 0.001), and drug
classification errors decreased (p < 0.001). There was a significant increase in
acquiring medication by replacing prescribed drugs with generics. Between 2002
and 2012 there was an increase in knowledge and use of generics, while perception
of lower prices and equivalent quality remained high.
PMID- 27487441
TI - Preparedness for the Rio 2016 Olympic Games: hospital treatment capacity in
georeferenced areas.
AB - Recently, Brazil has hosted mass events with recognized international relevance.
The 2014 FIFA World Cup was held in 12 Brazilian state capitals and health sector
preparedness drew on the history of other World Cups and Brazil's own experience
with the 2013 FIFA Confederations Cup. The current article aims to analyze the
treatment capacity of hospital facilities in georeferenced areas for sports
events in the 2016 Olympic Games in the city of Rio de Janeiro, based on a model
built drawing on references from the literature. Source of data were Brazilian
health databases and the Rio 2016 website. Sports venues for the Olympic Games
and surrounding hospitals in a 10km radius were located by geoprocessing and
designated a "health area" referring to the probable inflow of persons to be
treated in case of hospital referral. Six different factors were used to
calculate needs for surge and one was used to calculate needs in case of
disasters (20/1,000). Hospital treatment capacity is defined by the coincidence
of beds and life support equipment, namely the number of cardiac monitors
(electrocardiographs) and ventilators in each hospital unit. Maracana followed by
the Olympic Stadium (Engenhao) and the Sambodromo would have the highest single
demand for hospitalizations (1,572, 1,200 and 600, respectively). Hospital
treatment capacity proved capable of accommodating surges, but insufficient in
cases of mass casualties. In mass events most treatments involve easy clinical
management, it is expected that the current capacity will not have negative
consequences for participants.
PMID- 27487442
TI - [Smoking prevalence and associated factors among tobacco farmers in southern
Brazil].
AB - This study aimed to describe the prevalence of smoking and associated factors in
a cross-sectional population-based sample of 2,464 tobacco farmers in 2011.
Multivariate analysis in men assessed the association between smoking and
socioeconomic, behavioral, and occupational variables. Some 31.2% of men and 3.1%
of women were current smokers. In men, smoking was directly associated with age,
schooling, income, heavy drinking, time at work in tobacco farming, and time of
exposure to pesticides. Employment relationship was a risk factor for smoking,
and participation in religious activities was a protective factor. Male tobacco
farmers showed multiple risk behaviors and higher smoking prevalence than other
farmers. Ignoring the risk and cultural legacy may be common factors for these
behaviors and suggest combined approaches.
PMID- 27487443
TI - Frequency of self-reported sexual aggression and victimization in Brazil: a
literature review.
AB - The lack of official data on rape has been a challenge for researchers in Brazil.
Two recently published studies were based on law enforcement and medical records.
Although these studies represent important progress in research on rape in the
country, they have several limitations. In order to obtain more realistic rates,
the current article reviews Brazilian studies on self-reported sexual aggression
and victimization in individuals over 14 years of age. Forty-one studies were
identified through electronic searches and reference verification. From 1% to 40%
of women and 1% to 35% of men reported some form of victimization in the previous
year. The male perpetration incidence ranged from 2% to 44%. Despite the wide
variability, these rates were much higher than those provided by official data.
The results suggest that sexual orientation is associated with vulnerability.
Mixed findings were found concerning race. Most studies were based on convenience
samples and focused on female victimization. Male victimization has received
increasing attention, but studies on self-reported perpetration are still
limited.
PMID- 27487444
TI - [Mapping stakeholders' preferences in prioritization criteria for horizon
scanning in healthcare technologies].
AB - Filtration and prioritization are two basics steps in horizon scanning systems.
This article aimed to map stakeholders' preferences in the Brazilian Unified
National Health System (SUS) regarding filtration and prioritization criteria.
Two filtration criteria (time horizon and innovation) and eight prioritization
criteria (relevance to epidemiology, health policies, and clinical practice;
potential impact on SUS budget, healthcare providers' costs, and mortality;
safety; and legal, ethical, and social aspects) were selected. Multiple
correspondence analysis was used to map stakeholders' preferences within and
between groups. Two groups were more homogeneous and determinant for selection of
prioritization criteria. Stakeholders' professional experience had more influence
than institutional affiliations. The approach showed transparent criteria
selection and analysis of stakeholders' individual preferences.
PMID- 27487445
TI - [Equations for the evaluation of body composition in children and adolescents].
AB - Body mass index (BMI) is widely used in the world, despite caveats concerning its
interpretation in relation to gender, age, and race. BMI reading is normally
standardized, potentially producing error in the results and classification of
nutritional status. Body composition provides more relevant information than BMI:
fat mass and lean mass are the main indices. This paper reviews existing
equations and proposes the simplest ones and those with the lowest estimation
error to replace or complement BMI and improve interpretation of nutritional
status and physical activity.
PMID- 27487446
TI - Thiol oxidation by nitrosative stress: Cellular localization in human
spermatozoa.
AB - Peroxynitrite is a highly reactive nitrogen species and when it is generated at
high levels it causes nitrosative stress, an important cause of impaired sperm
function. High levels of peroxynitrite have been shown to correlate with
decreased semen quality in infertile men. Thiol groups in sperm are mainly found
in enzymes, antioxidant molecules, and structural proteins in the axoneme.
Peroxynitrite primarily reacts with thiol groups of cysteine-containing proteins.
Although it is well known that peroxynitrite oxidizes sulfhydryl groups in sperm,
the subcellular localization of this oxidation remains unknown. The main
objective of this study was to establish the subcellular localization of
peroxynitrite-induced nitrosative stress in thiol groups and its relation to
sperm motility in human spermatozoa. For this purpose, spermatozoa from healthy
donors were exposed in vitro to 3-morpholinosydnonimine (SIN-1), a compound which
generates peroxynitrite. In order to detect peroxynitrite and reduced thiol
groups, the fluorescent probes, dihydrorhodamine 123 and monobromobimane (mBBr),
were used respectively. Sperm viability was analyzed by propidium iodide
staining. Peroxynitrite generation and thiol redox state were monitored by
confocal microscopy whereas sperm viability was evaluated by flow cytometry.
Sperm motility was analyzed by CASA using the ISAS((r)) system. The results
showed that exposure of human spermatozoa to peroxynitrite results in increased
thiol oxidation which is mainly localized in the sperm head and principal piece
regions. Thiol oxidation was associated with motility loss. The high
susceptibility of thiol groups to peroxynitrite-induced oxidation could explain,
at least in part, the negative effect of reactive nitrogen species on sperm
motility. ABBREVIATIONS: DHR: dihydrorhodamine 123; mBBr: monobromobimane ONOO(
): peroxynitrite RNS: reactive nitrogen species RFI: relative fluorescence
intensity SIN-1: 3-morpholinosydnonimine CASA: Computer-Aided Sperm Analysis
PARP: poli ADP ribose polimerasa VCL: curvilinear velocity VSL: straight-line
velocity VAP: average path velocity PRDXs: peroxiredoxins ODF: outer dense fiber
ODF1: outer dense fiber 1 PI: propidium iodide DMSO: dimethyl sulfoxide SD:
standard deviation ANOVA: analysis of variance.
PMID- 27487447
TI - Nitrogen deposition does not enhance Sphagnum decomposition.
AB - Long-term additions of nitrogen (N) to peatlands have altered bryophyte growth,
species dominance, N content in peat and peat water, and often resulted in
enhanced Sphagnum decomposition rate. However, these results have mainly been
derived from experiments in which N was applied as ammonium nitrate (NH4NO3),
neglecting the fact that in polluted areas, wet deposition may be dominated
either by NO3(-) or NH4(+). We studied effects of elevated wet deposition of NO3(
) vs. NH4(+) alone (8 or 56kgNha(-1)yr(-1) over and above the background of
8kgNha(-1)yr(-1) for 5 to 11years) or combined with phosphorus (P) and potassium
(K) on Sphagnum quality for decomposers, mass loss, and associated changes in
hummock pore water in an ombrotrophic bog (Whim). Adding N, especially as NH4(+),
increased N concentration in Sphagnum, but did not enhance mass loss from
Sphagnum. Mass loss seemed to depend mainly on moss species and climatic factors.
Only high applications of N affected hummock pore water chemistry, which varied
considerably over time. Overall, C and N cycling in this N treated bog appeared
to be decoupled. We conclude that moss species, seasonal and annual variation in
climatic factors, direct negative effects of N (NH4(+) toxicity) on Sphagnum
production, and indirect effects (increase in pH and changes in plant species
dominance under elevated NO3(-) alone and with PK) drive Sphagnum decomposition
and hummock C and N dynamics at Whim.
PMID- 27487448
TI - PCDD, PCDF, dl-PCB and organochlorine pesticides monitoring in Sao Paulo City
using passive air sampler as part of the Global Monitoring Plan.
AB - The persistent organic pollutants (POPs), such as organochlorine pesticides and
PCBs, are ordinarily monitored in the aquatic environment or in soil in the
environmental quality monitoring programs in Sao Paulo, Brazil. One of the core
matrices proposed in the POPs Global Monitoring Plan (GMP) from the Stockholm
Convention list is the ambient air, which is not a usual matrix for POPs
monitoring in the country. In this study POP levels were evaluated in the air
samples from an urban site in Sao Paulo City over five years, starting in 2010 as
a capacity building project for Latin America and the Caribbean region for POP
monitoring in ambient air using passive samplers. Furthermore, after the end of
the Project in 2012, the monitoring continued in the same sampling site as means
to improving the analytical capacity building and contribute to the GMP data. The
POPs monitored were 17 congeners of 2,3,7,8 chloro-substituted PCDDs and PCDFs,
dioxin-like PCBs, indicator PCBs, organochlorine pesticides and toxaphene. The
results show a slight decrease in PCDD/F, dl-PCBs and indicator PCBs levels along
the five years. The organochlorine pesticide endosulfan was present at its
highest concentration at the beginning of the monitoring period, but it was below
detection level in the last year of the monitoring. Some other organochlorine
pesticides were detected close to or below quantitation limits. The compounds
identified were dieldrin, chlordane, alpha-HCH, gamma-HCH, heptachlor, heptachlor
epoxide, hexachlorobenzene and DDTs. Toxaphene congeners were not detected. These
results have confirmed the efficacy of passive sampling for POP monitoring and
the capacity building for POP analysis and monitoring was established. However
more needs to be done, including expansion of sampling sites, new POPs and
studies on sampling rates to be considered in calculating the concentration of
POPs in ambient air using a passive sampler.
PMID- 27487449
TI - Epigenetic and transcriptional regulation of autophagy.
AB - Macroautophagy (hereafter referred to as autophagy) is an essential self
digestion process to maintain homeostasis and promote survival in response to
starvation. Although the components of autophagy in the cytoplasm have been well
studied, little has been known about the fine-tuning mechanism of autophagy
through epigenetic regulations. Recently, we identified the histone arginine
methyltransferase CARM1 as a new component and followed histone H3R17
dimethylation as a critical epigenetic mark in starvation-induced autophagy. Upon
nutrient starvation, CARM1 is stabilized in the nucleus, but not in the
cytoplasm, whereas it is constantly degraded under nutrient-rich conditions by
the SKP2-containing SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase. We further
showed that nutrient starvation induces the protein levels and activity of AMPK
in the nucleus. Activated AMPK then phosphorylates FOXO3, leading to SKP2
downregulation and increased CARM1 protein levels in the nucleus. Stabilized
CARM1 in turn functions as an essential co-activator of TFEB and regulates the
expression of autophagy and lysosomal genes. Our findings provide a conceptual
advance that activation of specific epigenetic programs is indispensable for a
sustained autophagic response, and shed light on a potential therapeutic
targeting of the newly identified AMPK-SKP2-CARM1 signaling axis in autophagy
related diseases.
PMID- 27487450
TI - Development and validation of a new serum standard for the measurement of anti
HEV antibodies in animals.
AB - Although hepatitis E virus (HEV) infection is a zoonosis, there is, currently, no
standardized assay for quantitatively measuring anti-HEV antibody levels in HEV
animal reservoirs. In this study, anti-HEV antibody positive serum from a rabbit
(RS26) was calibrated by dose-response parallel line assay using the World Health
Organization (WHO) reference standard for anti-HEV antibodies. After evaluating
the stability of the RS26 serum, a quantification assay of anti-HEV antibodies
using RS26 as a standard was developed and evaluated for both reproducibility and
suitability to field studies. The anti-HEV antibody level of RS26 was calculated
to be 39.54 IU/ml. A series of standard working serum for anti-HEV antibodies
consisted of five serum dilutions (3.950 IU/ml, 1.975 IU/ml, 0.986 IU/ml, 0.494
IU/ml, and 0.247 IU/ml). The quantitative assay using RS26 showed good range and
reproducibility, effectively measuring the dynamics of anti-HEV antibody
concentrations in pigs and rabbits. In conclusion, we have developed a a stable
and reproducible serum standard for the quantitation of anti-HEV antibodies. J.
Med. Virol. 89:497-501, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27487451
TI - Action of Caffeine as an Amyloid Inhibitor in the Aggregation of Abeta16-22
Peptides.
AB - Alzheimer's disease (AD) is a neurodegenerative disease caused due to aggregation
of Abeta peptides in the brain tissues. Recently, several studies on AD
transgenic mice have shown the effect of caffeine in significantly reducing the
Abeta amyloid level in their brains. However, the mechanism and mode of caffeine
action on amyloid aggregation are not known. Therefore, in this study, we have
carried out molecular dynamics simulations of five amyloid-forming Abeta16-22
peptides in pure water and in a regime of caffeine solutions, with different
caffeine/peptide stoichiometric ratios. The secondary structure analyses of
peptides in pure water show the formation of beta-sheet conformations, whereas on
addition of caffeine, these ordered conformations become negligible. The radial
distribution function, contact map, nonbonding interaction energy, hydrogen
bonding, potential of mean force, and hydration analyses show that there is less
interpeptide interaction in the presence of caffeine, and the effect is greater
with an increasing caffeine ratio. The interaction of aromatic phenylalanine
residues of peptides with caffeine restricts the interpeptide interaction
tendency. Upon increasing the number of caffeine molecules, interaction of
caffeine with other hydrophobic residues also increases. Thus, the hydrophobic
core-recognition motif of amyloid formation of peptides is physically blocked by
caffeine, thereby abolishing the self-assembly formation.
PMID- 27487452
TI - The CREB-binding protein affects the circadian regulation of behaviour.
AB - Rhythmic changes in light and temperature conditions form the primary
environmental cues that synchronize the molecular circadian clock of most species
with the external cycles of day and night. Previous studies established a role
for the CREB-binding protein (CBP) in molecular clock function by coactivation of
circadian transcription. Here, we report that moderately increased levels of CBP
strongly dampen circadian behavioural rhythms without affecting molecular
oscillations of circadian transcription. Interestingly, light-dark cycles as well
as high temperature facilitated a circadian control of behavioural activity.
Based on these observations we propose that in addition to its coactivator
function for circadian transcription, CBP is involved in the regulation of
circadian behaviour down-stream of the circadian clock.
PMID- 27487453
TI - van der Waals Heteroepitaxy of Germanene Islands on Graphite.
AB - We fabricated flat, two-dimensional germanium sheets showing a honeycomb lattice
that matches that of germanene by depositing submonolayers of Ge on graphite at
room temperature and subsequent annealing to 350 degrees C. Scanning tunneling
microscopy shows that the germanene islands have a small buckling with no atomic
reconstruction and does not give any hints for alloy formation and hybridization
with the substrate. Our density functional theory calculations of the structural
properties agree well with our experimental findings and indicate that the
germanene sheet interacts only weakly with the substrate underneath. Our band
structure calculations confirm that the Dirac cone of free-standing germanene is
preserved for layers supported on graphite. The germanene islands show a small
but characteristic charge transfer with the graphite substrate which is predicted
by our ab initio simulations in excellent agreement with scanning tunneling
spectroscopy measurements.
PMID- 27487455
TI - Natural Compounds as Inhibitors of Tyrosyl-tRNA Synthetase.
AB - Tyrosyl-tRNA synthetases (TyrRSs) as essential enzymes for all living organisms
are good candidates for therapeutic target in the prevention and therapy of
microbial infection. We examined the effect of various polyphenols, alkaloids,
and terpenes-secondary metabolites produced by higher plants showing many
beneficial properties for the human organism, on bacterial aminoacylation
reaction. The most potent inhibitors of Escherichia coli TyrRS are
epigallocatechin gallate, acacetin, kaempferide, and chrysin, whereas the enzymes
from Staphylococcus aureus and Pseudomonas aeruginosa are inhibited mainly by
acacetin and chrysin. Most of them act as competitive inhibitors. Structure
activity relationship showed that the most potent flavonoid inhibitors contain
hydroxyl group at position 5 and 7 of A ring and OCH3 group at position 4' of B
ring.
PMID- 27487454
TI - Visceral Adipose Tissue Is Associated With Bone Microarchitecture in the
Framingham Osteoporosis Study.
AB - Obesity has been traditionally considered to protect the skeleton against
osteoporosis and fracture. Recently, body fat, specifically visceral adipose
tissue (VAT), has been associated with lower bone mineral density (BMD) and
increased risk for some types of fractures. We studied VAT and bone
microarchitecture in 710 participants (58% women, age 61.3 +/- 7.7 years) from
the Framingham Offspring cohort to determine whether cortical and trabecular BMD
and microarchitecture differ according to the amount of VAT. VAT was measured
from CT imaging of the abdomen. Cortical and trabecular BMD and microarchitecture
were measured at the distal tibia and radius using high-resolution peripheral
quantitative computed tomography (HR-pQCT). We focused on 10 bone parameters:
cortical BMD (Ct.BMD), cortical tissue mineral density (Ct.TMD), cortical
porosity (Ct.Po), cortical thickness (Ct.Th), cortical bone area fraction
(Ct.A/Tt.A), trabecular density (Tb.BMD), trabecular number (Tb.N), trabecular
thickness (Tb.Th), total area (Tt.Ar), and failure load (FL) from micro-finite
element analysis. We assessed the association between sex-specific quartiles of
VAT and BMD, microarchitecture, and strength in all participants and stratified
by sex. All analyses were adjusted for age, sex, and in women, menopausal status,
then repeated adjusting for body mass index (BMI) or weight. At the radius and
tibia, Ct.Th, Ct.A/Tt.A, Tb.BMD, Tb.N, and FL were positively associated with VAT
(all p-trend <0.05), but no other associations were statistically significant
except for higher levels of cortical porosity with higher VAT in the radius. Most
of these associations were only observed in women, and were no longer significant
when adjusting for BMI or weight. Higher amounts of VAT are associated with
greater BMD and better microstructure of the peripheral skeleton despite some
suggestions of significant deleterious changes in cortical measures in the non
weight bearing radius. Associations were no longer significant after adjustment
for BMI or weight, suggesting that the effects of VAT may not have a substantial
effect on the skeleton independent of BMI or weight. (c) 2016 American Society
for Bone and Mineral Research.
PMID- 27487456
TI - Practice Patterns and Outcomes Associated With Use of Anticoagulation Among
Patients With Atrial Fibrillation During Sepsis.
AB - IMPORTANCE: Atrial fibrillation (AF) during sepsis is associated with an
increased risk of ischemic stroke during hospitalization, but risks and benefits
associated with anticoagulation for AF during sepsis are unclear. OBJECTIVE: To
determine clinician practice patterns and patient risk of stroke and bleeding
associated with use of anticoagulation for AF during sepsis. DESIGN, SETTING, AND
PARTICIPANTS: A retrospective cohort study using enhanced administrative claims
data from approximately 20% of patients hospitalized in the United States July 1,
2010, to June 30, 2013, examined patients with AF during sepsis who did not have
additional indications for therapeutic anticoagulation. Propensity score and
instrumental variable analyses were used to evaluate risks of in-hospital stroke
and bleeding associated with anticoagulation during sepsis. EXPOSURES: Parenteral
anticoagulants administered in doses greater than those used for prophylaxis of
venous thromboembolism. MAIN OUTCOMES AND MEASURES: Ischemic stroke and
clinically significant bleeding events during hospitalization. RESULTS: Of 113
511 patients hospitalized with AF and sepsis, 38 582 were included in our primary
analysis (18 976 men and 19 606 women; mean [SD] age, 74.9 [11.7] years). A total
of 13 611 patients (35.3%) received parenteral anticoagulants, while 24 971
(64.7%) did not. Hospital utilization rates of parenteral anticoagulants for AF
during sepsis varied (median, 33%; 25th-75th percentile, 25%-43%). CHA2DS2VASc
scores (congestive heart failure, hypertension, age >=75 years [doubled], type 1
or type 2 diabetes, stroke or transient ischemic attack or thromboembolism
[doubled], vascular disease [prior myocardial infarction, peripheral artery
disease, or aortic plaque], age 65-75 years, sex category [female]) poorly
discriminated the risk of ischemic stroke during sepsis (C statistic, 0.526).
Among 27 010 propensity score-matched patients, rates of in-hospital ischemic
stroke events did not differ significantly between patients who did (174 of 13
505 [1.3%]) and did not (185 of 13 505 [1.4%]) receive parenteral anticoagulation
(relative risk [RR], 0.94; 95% CI, 0.77-1.15). Clinically significant bleeding
occurred more often among patients who received parenteral anticoagulation (1163
of 13 505 [8.6%]) than patients who did not receive parenteral anticoagulation
(979 of 13 505 [7.2%]; RR, 1.21; 95% CI, 1.10-1.32). Risk of ischemic stroke
associated with parenteral anticoagulation did not differ significantly between
patients with preexisting (RR, 1.12; 95% CI, 0.86-1.44) or newly diagnosed AF
(RR, 0.85; 95% CI 0.57-1.27; P = .31 for interaction). Results were robust to
multiple sensitivity analyses, including hospital utilization rates of parenteral
anticoagulation for AF as an instrument for anticoagulation exposure (RR for
stroke, 1.08; 95% CI, 0.62-1.90; RR for bleeding, 1.23; 95% CI, 0.88-1.72).
CONCLUSIONS AND RELEVANCE: Among patients with AF during sepsis, parenteral
anticoagulation was not associated with reduced risk of ischemic stroke and was
associated with higher bleeding rates.
PMID- 27487457
TI - Gene-regulatory networks controlling inflorescence and flower development in
Arabidopsis thaliana.
AB - Reproductive development in plants is controlled by complex and intricate gene
regulatory networks of transcription factors. These networks integrate the
information from endogenous, hormonal and environmental regulatory pathways. Many
of the key players have been identified in Arabidopsis and other flowering plant
species, and their interactions and molecular modes of action are being
elucidated. An emerging theme is that there is extensive crosstalk between
different pathways, which can be accomplished at the molecular level by
modulation of transcription factor activity or of their downstream targets. In
this review, we aim to summarize current knowledge on transcription factors and
epigenetic regulators that control basic developmental programs during
inflorescence and flower morphogenesis in the model plant Arabidopsis thaliana.
This article is part of a Special Issue entitled: Plant Gene Regulatory
Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan Springer.
PMID- 27487458
TI - Plant responses to abiotic stress: The chromatin context of transcriptional
regulation.
AB - The ability of plants to cope with abiotic environmental stresses such as
drought, salinity, heat, cold or flooding relies on flexible mechanisms for re
programming gene expression. Over recent years it has become apparent that
transcriptional regulation needs to be understood within its structural context.
Chromatin, the assembly of DNA with histone proteins, generates a local higher
order structure that impacts on the accessibility and effectiveness of the
transcriptional machinery, as well as providing a hub for multiple protein
interactions. Several studies have shown that chromatin features such as histone
variants and post-translational histone modifications are altered by
environmental stress, and they could therefore be primary stress targets that
initiate transcriptional stress responses. Alternatively, they could act
downstream of stress-induced transcription factors as an integral part of
transcriptional activity. A few experimental studies have addressed this 'chicken
and-egg' problem in plants and other systems, but to date the causal relationship
between dynamic chromatin changes and transcriptional responses under stress is
still unclear. In this review we have collated the existing information on
concurrent epigenetic and transcriptional responses of plants to abiotic stress,
and we have assessed the evidence using a simple theoretical framework of
causality scenarios. This article is part of a Special Issue entitled: Plant Gene
Regulatory Mechanisms and Networks, edited by Dr. Erich Grotewold and Dr. Nathan
Springer.
PMID- 27487459
TI - Pericyclic Cascade toward Isochromenes: Application to the Synthesis of Alkaloid
Benzosimuline.
AB - The synthesis of biologically active alkaloid benzosimuline, isolated from the
shrub Zanthoxylum simulans, is reported. Key transformation involves an oxa-6pi
electrocyclic ring-opening/hetero-Diels-Alder pericyclic cascade. Although the
last aromatization step proved to be cumbersome, this work unfolds a unique route
to access interesting molecules from simple precursors.
PMID- 27487460
TI - High Efficiency Organic Solar Cells Achieved by the Simultaneous Plasmon-Optical
and Plasmon-Electrical Effects from Plasmonic Asymmetric Modes of Gold Nanostars.
AB - The plasmon-optical effects have been utilized to optically enhance active layer
absorption in organic solar cells (OSCs). The exploited plasmonic resonances of
metal nanomaterials are typically from the fundamental dipole/high-order modes
with narrow spectral widths for regional OSC absorption improvement. The
conventional broadband absorption enhancement (using plasmonic effects) needs
linear-superposition of plasmonic resonances. In this work, through strategic
incorporation of gold nanostars (Au NSs) in between hole transport layer (HTL)
and active layer, the excited plasmonic asymmetric modes offer a new approach
toward broadband enhancement. Remarkably, the improvement is explained by energy
transfer of plasmonic asymmetric modes of Au NS. In more detail, after
incorporation of Au NSs, the optical power in electron transport layer transfers
to active layer for improving OSC absorption, which otherwise will become
dissipation or leakage as the role of carrier transport layer is not for photon
absorption induced carrier generation. Moreover, Au NSs simultaneously deliver
plasmon-electrical effects which shorten transport path length of the typically
low-mobility holes and lengthen that of high-mobility electrons for better
balanced carrier collection. Meanwhile, the resistance of HTL is reduced by Au
NSs. Consequently, power conversion efficiency of 10.5% has been achieved through
cooperatively plasmon-optical and plasmon-electrical effects of Au NSs.
PMID- 27487461
TI - Mechanistically Inspired Route toward Hexahydro-2H-chromenes via Consecutive [4 +
2] Cycloadditions.
AB - Utilizing two robust C-C bond-forming reactions, the Baylis-Hillman reaction and
the Diels-Alder reaction, we report a highly enantio-, regio-, and
diastereoselective synthesis of hexahydro-2H-chromenes via two sequential [4 + 2]
cycloadditions. These tandem and formal cycloadditions have also been performed
as a "one-pot" sequence to access the corresponding heterocycles constituting up
to five contiguous stereocenters in excellent yields and stereoselectivity.
PMID- 27487462
TI - Cancer Survivors Who Play Recreational Computer Games: Motivations for Playing
and Associations with Beneficial Psychological Outcomes.
AB - OBJECTIVE: Playing recreational videogames is a common activity, yet little is
known about its role in the lives of people who are coping with serious illness.
These individuals may experience depression and isolation and may turn to games
to help alleviate negative experiences and support well-being. We explored these
possibilities in the context of cancer survivors. The study aimed to discover
motivations underlying game play and the extent to which motivations are
associated with psychological health and well-being. METHODS: We conducted a
cross-sectional online survey of survivors who play recreational games (N = 794).
Key variables were motivations and indicators of psychological health, including
self-efficacy in cancer communications, resilient coping, and beliefs that one is
living a fulfilling and meaningful life (flourishing). RESULTS: Participants were
most likely to be motivated to play for stimulation and a sense of accomplishment
(intrinsic rewards), followed by development of self, sense of community, and
personal affirmation. Multiple regression analyses revealed positive associations
between playing for intrinsic rewards and all three psychological health
outcomes. Playing for a sense of community was also positively associated with
coping and flourishing. CONCLUSION: Playing recreational videogames, particularly
to receive intrinsic rewards and to connect with others, may play a supportive
role in the psychological health of survivors. Findings suggest future areas for
research and implications for development of serious games.
PMID- 27487463
TI - Efficacy of Topical Ofloxacin 0.3 % Administration on Conjunctival Bacterial
Flora in Diabetic Patients Undergoing Intravitreal Injections.
AB - PURPOSE: This prospective, randomized case series study aims to evaluate the
efficacy of ofloxacin 0.3% eye drops in eradication of conjunctival bacterial
flora in diabetic patients undergoing intravitreal injections (IVI). METHODS:
Ninety-two diabetic patients (92 eyes) scheduled to undergo intravitreal
injection of ranibizumab due to diabetic macular edema were enrolled in the
study. Patients were randomly assigned to three different groups. Group 1 (n=32)
received ofloxacin eye drops the day before before IVI (four times); patients in
Group 2 (n=29) were administered ofloxacin one hour before IVI (every 15
minutes), while Group 3 (n=31) comprised patients that received combined
administration of ofloxacin both one day and one hour before IVI (eight doses).
Samples were collected from the injection site before and after antibiotic
administration. Culture results from BACTEC broth and positive cultures in blood
agar and Sabouraud's dextrose agar plates were measured. RESULTS: In Group 1,
BACTEC broth positive cultures decreased from 84.4% at baseline to 50% after
ofloxacin administration (p=0.007), and blood agar positive cultures reduced from
65.63% to 34.38% (p=0.02). In Group 2, positive cultures significantly decreased
in BACTEC broth (from 79.3% at baseline to 48.28%; p=0.027) and in blood agar
(from 68.97% to 37.13%; p=0.034). In Group 3, positive cultures decreased from
77.42% at baseline to 32.26% (p=0.0008) and from 58.06% at baseline to 22.58%
(p=0.009) in BACTEC broth and blood agar, respectively. No microorganisms were
isolated from Sabouraud's dextrose agar plates. CONCLUSIONS: The combined one
day/one hour (eight doses) ofloxacin administration in diabetic patients is
extremely effective in reducing conjunctival bacterial flora. The application of
topical ofloxacin for one day or one hour before IVI is also significantly
effective.
PMID- 27487464
TI - Why is preconception health and care important?
PMID- 27487465
TI - Effect of phosphonate monolayer adsorbate on the microwave photoresponse of TiO2
nanotube membranes mounted on a planar double ring resonator.
AB - In this study, the effects of a phosphonate molecular monolayer adsorbed on the
surface of a free-standing self-organized TiO2 nanotube membrane, on the
microwave photoresponse of the membrane are presented. This phenomenon is
monitored using planar microwave sensors. A double ring resonator is utilized to
monitor the permittivity and conductivity variation on the monolayer coated
membrane and the sensor environment separately. It is shown that the rise time
and subsequent decay of the amplitude (A), resonance frequency (f 0) and quality
factor (Q) of the resonator depend on the existence and the type of the monolayer
coating the membrane. Three different monolayers of n-decylphosphonic acid (DPA),
1H, 1H', 2H, 2H'-perfluorodecyl phosphonic acid (PFDPA) and 16
phosphonohexadecanoic acid adsorbed on the titania nanotube membrane are
investigated while monitoring their microwave properties during the illumination
time period and in the relaxation period, which demonstrate different behavior in
comparison to each other and to the bare nanotube membrane layer. The effect of
humidity on the TiO2 nanotube membrane with and without different monolayers is
also studied and the results demonstrate distinguishable microwave responses.
While each of the monolayer-coated membranes exhibited an attenuation of the
photo-induced change in A, f 0 and Q with respect to the bare membrane, PFDPA
coated membranes showed the smallest relative change in the monitored microwave
parameters upon ultraviolet illumination and upon the introduction of different
levels of humidity. These effects are explained on the basis of surface trap
passivation by the monolayers as well as the hydrophobicity of the monolayers.
Our work also shows how the interactions of self-assembled monolayers with charge
carriers and surface states on metal oxides may be used to indirectly sense their
presence through measurement of the microwave response.
PMID- 27487467
TI - The formation and characteristics of the i-motif structure within the promoter of
the c-myb proto-oncogene.
AB - C-myb proto-oncogene is a potential therapeutic target for some human solid
tumors and leukemias. A long cytosine-rich sequence, which locates the downstream
of the transcription initiation site, is demonstrated to fold into an
intramolecular i-motif DNA using electrospray ionization mass spectrometry (ESI
MS) and circular dichroism (CD) spectroscopy. Effects of factors, including the
pH value, the number of C:C(+) dimers, the concentration of buffer, the molecular
crowding condition, and the coexistence of the complementary DNA, on the
formation and the structural stability of the i-motif DNA are systematically
studied. We have demonstrated that the i-motif folding in the c-myb promoter
could be accelerated upon synergistic physiological stimuli including
intracellular molecular crowding and low pH values, as well as the large number
of the i-motif C:C(+) dimers. Meanwhile, various inputs, such as acids/bases and
metal ions, have exhibited their abilities in controlling the conformational
switch of the c-myb GC-rich DNA. Acidic pH values and the presence of K(+) ions
can induce the dissociation of the double helix. Our present strategy can greatly
extend the potential usages of i-motif DNA molecules with specific sequences as
conformational switch-controlled devices. Moreover, this work demonstrates the
superiority of CD spectroscopy associated with ESI-MS as a rapid, more cost
effective and sensitive structural change responsive method in the research of
DNA conformational switching.
PMID- 27487468
TI - A hermeneutic phenomenological study exploring the experience health
practitioners have when working with families to safeguard children and the
invisibility of the emotions work involved.
AB - AIMS AND OBJECTIVES: To explore the emotions work undertaken by practitioners
with responsibility for the safeguarding of child well-being and establish
whether there is a relationship between emotion work, role visibility,
professional well-being and effectiveness of supportive frameworks. BACKGROUND:
Protecting children is the responsibility of everyone in society with health,
social care and public health services leading this worldwide. To safeguard
children effectively, it is known that practitioners build relationships with
families in sometimes challenging situations, which involve the management of
emotions. However, irrespective of this current knowledge; health practitioners
who work in this area suggest that their child safeguarding role is not
recognised, respected or valued in professional and societal settings. The
purpose of this study was to report on a qualitative study which set out to
explore the relationship between the known relational-based emotions work of
practitioners' and the reported lack of visibility. METHODS: Hermeneutic
phenomenology underpinned the study. Semistructured interviews were employed for
data collection. Ten participants actively working with preschool children and
families in healthcare organisations were recruited. RESULTS: The emotional-,
relationship- and communicative-based work crucial to effectively safeguard
children may influence the visibility of the role. Poor role visibility
influences the morale of practitioners and the support they receive. CONCLUSION:
In conclusion this study proposes that when there is poor role recognition; there
is ineffective clinical support. This reduces professional well-being, which in
turn will impact practitioner abilities to safeguard children. RELEVANCE TO
CLINICAL PRACTICE: This study highlights that to sustain safe and effective
health and social care practice, organisational leads require an understanding of
the impact emotional- and relational-based work can have on practitioners and
provide supportive frameworks that will effectively promote professional well
being.
PMID- 27487471
TI - Ab Initio Benchmark Study of Nonadiabatic S1-S2 Photodynamics of cis- and trans
Hexatriene.
AB - The dynamics of the nonadiabatically coupled lowest singlet excited states of cis
and trans-hexatriene are studied theoretically, in a comprehensive electronic
structure and quantum dynamical investigation. At the ground state equilibrium
geometry the relevant S2 and S1 states carry the A1 (Ag) and B2 (Bu) symmetry
labels, for the cis (trans) isomer. Various high-level electronic structure
methods are used, including the recently reparametrized DFT/MRCI method, and the
results are critically compared. Key parameters of interest are the vertical
energy gap and the strength of vibronic coupling between the interacting
electronic states. To estimate their influence, suitable comparison calculations
are performed. The results are used as the basis for quantum dynamical
calculations on the UV absorption spectrum and electronic population transfer
involving the S1 and S2 states. Up to nine nonseparable degrees of freedom are
included in the calculations. The experimental UV absorption spectrum in the 5
5.2 eV energy range can be very well reproduced. The time-dependent wavepacket
propagations reveal a population transfer on the order of 30-50 fs, which becomes
increasingly complete with more degrees of freedom included in the calculation.
The results are briefly compared with analogous data for the s-trans-butadiene
system treated by some of us recently.
PMID- 27487469
TI - Migratory and adhesive cues controlling innate-like lymphocyte surveillance of
the pathogen-exposed surface of the lymph node.
AB - Lymph nodes (LNs) contain innate-like lymphocytes that survey the subcapsular
sinus (SCS) and associated macrophages for pathogen entry. The factors promoting
this surveillance behavior have not been defined. Here, we report that
IL7R(hi)Ccr6(+) lymphocytes in mouse LNs rapidly produce IL17 upon bacterial and
fungal challenge. We show that these innate-like lymphocytes are mostly LN
resident. Ccr6 is required for their accumulation near the SCS and for efficient
IL17 induction. Migration into the SCS intrinsically requires S1pr1, whereas
movement from the sinus into the parenchyma involves the integrin LFA1 and its
ligand ICAM1. CD169, a sialic acid-binding lectin, helps retain the cells within
the sinus, preventing their loss in lymph flow. These findings establish a role
for Ccr6 in augmenting innate-like lymphocyte responses to lymph-borne pathogens,
and they define requirements for cell movement between parenchyma and SCS in what
we speculate is a program of immune surveillance that helps achieve LN barrier
immunity.
PMID- 27487470
TI - Gating of reafference in the external cuneate nucleus during self-generated
movements in wake but not sleep.
AB - Nervous systems distinguish between self- and other-generated movements by
monitoring discrepancies between planned and performed actions. To do so,
corollary discharges are conveyed to sensory areas and gate expected reafference.
Such gating is observed in neonatal rats during wake-related movements. In
contrast, twitches, which are self-generated movements produced during active (or
REM) sleep, differ from wake movements in that they reliably trigger robust
neural activity. Accordingly, we hypothesized that the gating actions of
corollary discharge are absent during twitching. Here, we identify the external
cuneate nucleus (ECN), which processes sensory input from the forelimbs, as a
site of movement-dependent sensory gating during wake. Whereas pharmacological
disinhibition of the ECN unmasked wake-related reafference, twitch-related
reafference was unaffected. This is the first demonstration of a neural
comparator that is differentially engaged depending on the kind of movement
produced. This mechanism explains how twitches, although self-generated, trigger
abundant reafferent activation of sensorimotor circuits in the developing brain.
PMID- 27487472
TI - Evaluation of Motivational Interviewing to Improve Psychotropic Medication
Adherence in Adolescents.
AB - PROBLEM: Medication adherence rates in adolescents are poor. The World Health
Organization identified that those at greatest risk were nonwhite adolescents
with depression. Medication nonadherence results in poorer mental health
outcomes. OBJECTIVE: The first aim of the study was to investigate if two
motivational interviewing (MI) sessions would improve medication adherence in
adolescents taking antidepressants and mood stabilizers. The second aim was to
evaluate if attitudes toward medication correlated with adherence. The third aim
was to determine if self-reported adherence scores were similar to electronic
adherence data collected. METHODS: The quasi-experimental study contained an MI
intervention, including a baseline and postintervention assessment of adherence
over 30 days. A total of 48 adolescents, ranging in age from 12 to 18 years, were
recruited from a university mental health center to participate in the study; 41
completed the study. Four nurse practitioners and two child psychiatrists
mastered the MI techniques evaluated with standardized measures. The Medication
Electronic Monitoring System (MEMS) was the primary measure of medication
adherence. The Drug Attitude Inventory (DAI) was used as a secondary measure.
Finally, participants completed the client evaluation of MI and a satisfaction
survey of MI. RESULTS: At endpoint, 70.7% of the participants were taking their
medications between 80% and 100% of the time, as measured over 30 days, compared
with 43.9% of participants at baseline. Mean adherence scores significantly
improved by 17% after two MI sessions. Mean baseline adherence scores were 63.7%,
whereas mean endpoint adherence scores were 80.6% (p < 0.0001). The effect size
was 0.65, demonstrating moderate effect. Participants (n = 29) who demonstrated
80% or greater adherence had DAI mean scores of 16.48, whereas those below 80%
had a DAI mean of 15.5 (p = 0.73), demonstrating no significant difference on
drug attitudes between the two groups at endpoint. DAI baseline mean scores were
14.2, whereas endpoint mean scores were 16.2. There was a significant difference
between self-rated adherence and objective data collected from the MEMS caps as
participants over-reported medication adherence by an average of 18.4% at
baseline (t = 6.84, df = 40, p < 0.001). Participants reported a high degree of
satisfaction with MI. CONCLUSIONS: MI is a promising intervention for adolescents
to improve psychotropic medication adherence.
PMID- 27487473
TI - Rupture of the pregnant uterus - a 20-year review.
AB - OBJECTIVES: To examine the incidence, causative factors, maternal and foetal
outcomes and subsequent fertility in cases of uterine rupture in scarred and
unscarred uteri. METHODS: A 20 years' retrospective review was carried out where
relevant data were collected from the medical records. Outcome measures included
labour characteristics, operative procedures, maternal and perinatal outcome in
addition to subsequent fertility. RESULTS: Forty-nine cases of complete uterine
rupture were identified. Women in the unscarred group were older, had higher
parity and heavier babies (p values < 0.05). Alternatively, the scarred group
cases were associated with more silent rupture discovered at time of surgery,
recession of the presenting part and more visceral involvement in particularly
the urinary bladder. Admission to NICU and birth asphyxia were more frequent in
the scarred group while stillbirth and early neonatal death were more common in
the unscarred one. Twenty-four out of 49 cases had repair with no bilateral tubal
ligation and out of these, 13 patients subsequently conceived and had 22 babies.
CONCLUSION: Physicians should be vigilant to the risk factors and clinical
presentations of uterine rupture during pregnancy. Cautious attempts to repair
the ruptured uterus should be tried for patients' wellbeing and to help maintain
fertility.
PMID- 27487475
TI - MiR-329 suppresses osteosarcoma development by downregulating Rab10.
AB - MiR-329 has been proved to be a tumor suppressor gene in various malignancies,
however, its role in osteosarcoma remains elusive. We found that miR-329 is
remarkably downregulated in osteosarcoma tissues and relates to advanced stages.
MiR-329 is able to inhibit osteosarcoma cell proliferation, promote apoptosis,
and induce G0/G1 cell cycle arrest. In addition, miR-329 also suppresses wound
healing and migration ability of osteosarcoma cells and inhibits tumorigenicity
in vivo. Rab10 was identified as a target of miR-329 in osteosarcoma and mediates
its biofunction. These findings may shed light to the understanding of tumor
development in osteosarcoma.
PMID- 27487474
TI - Selective endosomal microautophagy is starvation-inducible in Drosophila.
AB - Autophagy delivers cytosolic components to lysosomes for degradation and is thus
essential for cellular homeostasis and to cope with different stressors. As such,
autophagy counteracts various human diseases and its reduction leads to aging
like phenotypes. Macroautophagy (MA) can selectively degrade organelles or
aggregated proteins, whereas selective degradation of single proteins has only
been described for chaperone-mediated autophagy (CMA) and endosomal
microautophagy (eMI). These 2 autophagic pathways are specific for proteins
containing KFERQ-related targeting motifs. Using a KFERQ-tagged fluorescent
biosensor, we have identified an eMI-like pathway in Drosophila melanogaster. We
show that this biosensor localizes to late endosomes and lysosomes upon prolonged
starvation in a KFERQ- and Hsc70-4- dependent manner. Furthermore, fly eMI
requires endosomal multivesicular body formation mediated by ESCRT complex
components. Importantly, induction of Drosophila eMI requires longer starvation
than the induction of MA and is independent of the critical MA genes atg5, atg7,
and atg12. Furthermore, inhibition of Tor signaling induces eMI in flies under
nutrient rich conditions, and, as eMI in Drosophila also requires atg1 and atg13,
our data suggest that these genes may have a novel, additional role in regulating
eMI in flies. Overall, our data provide the first evidence for a novel,
starvation-inducible, catabolic process resembling endosomal microautophagy in
the Drosophila fat body.
PMID- 27487476
TI - Light energy attenuation through orthodontic ceramic brackets at different
irradiation times.
AB - OBJECTIVE: To evaluate the total light energy (TLE) transmission through three
types of ceramic brackets with, bracket alone and with the addition of
orthodontic adhesive, at different exposure durations, and to compare the
microhardness of the cured adhesive. MATERIALS AND METHODS: Three different makes
of ceramic brackets, Pure Sapphire(M), ClarityTM ADVANCED(P) and Dual Ceramic(P)
were used. Eighteen specimens of each make were prepared and allocated to three
groups (n = 6). MARC((r))-resin calibrator was used to determine the light curing
unit (LCU) tip irradiance (mW/cm(2)) and TLE (J/cm(2)) transmitted through the
ceramic brackets, and through ceramic bracket plus TransbondTM XT Light Cure
Adhesive, for 5, 10 and 20 s. Vickers-hardness values at the bottom of the cured
adhesive were determined. Statistical analysis used one-way analysis of variance
(ANOVA); P = 0.05. RESULTS: TLE transmission rose significantly among all samples
with increasing exposure durations. TLE reaching the adhesive- enamel interface
was less than 10 J/cm(2), and through monocrystalline and polycrystalline ceramic
brackets was significantly different (P < 0.05). Pure Sapphire(M) showed the
highest amount of TLE transmission and Vickers-hardness values for 5, 10 and 20
s. CONCLUSION: Following manufacturer's recommendations, insufficient TLE may be
delivered to the adhesive: increasing the exposure durations may be required when
adhesive is cured through ceramic brackets. Clinicians are advised to measure the
tip irradiance of their LCUs and increase curing time beyond 5 s. Orthodontic
clinicians should understand the type of light curing device and the orthodontic
adhesive used in their practice.
PMID- 27487477
TI - H2O2/DMSO-Promoted Regioselective Synthesis of 3,3'-Bisimidazopyridinylmethanes
via Intermolecular Oxidative C(sp(2))-H Bond Activation of Imidazoheterocycles.
AB - In the past decade, metal-free approaches for C-C bond formation have attracted a
great deal of attention due to their ease of use and low cost. This report
represents a novel and metal-free synthesis of 3,3'-bisimidazopyridinylmethanes
via intermolecular oxidative C(sp(2))-H bond functionalization of imidazo[1,2
a]pyridines with dimethyl sulfoxide as the carbon synthon (CH2) using H2O2 as a
mild oxidant under air. A library of 3,3'-bis(2-arylimidazo[1,2-a]pyridin-3
yl)methanes has been achieved in good to excellent yields. The present
methodology has been successfully applied to imidazo[2,1-b]thiazoles and
imidazo[2,1-b]benzothiazoles. Furthermore, the current approach was also extended
for the synthesis of unsymmetrical 3,3'-bisimidazopyridinylmethanes under
optimized reaction conditions. A mechanistic pathway is proposed on the basis of
experiments with radical scavengers and DMSO-d6 and ESI-MS observations.
PMID- 27487478
TI - Assessing patient outcomes and cost-effectiveness of nurse-led follow-up for
women with breast cancer - have relevant and sensitive evaluation measures been
used?
AB - AIMS AND OBJECTIVES: To explore how interventions using nurse-led follow-up in
breast cancer care have been evaluated with a focus on patient outcomes and cost
effectiveness. BACKGROUND: As part of the advancement of breast care, nurse-led
follow-up is increasingly used as an alternative to routine hospital follow-up in
outpatient clinics. There is evidence suggesting that patients appear to be
satisfied with the nurse-led follow-up, but there is a lack of evidence of
whether this perception equates to patients' satisfaction with the model of
physician-led follow-up. DESIGN: Systematic review. METHOD: Three databases were
searched, and 29 RCT were initially screened. Finally, 13 articles were
critically appraised. Searches included articles between 2005-2013. The quality
of appraisal assessment was inspired by the GRADE system. RESULTS: The results
show that there are many different instruments used when evaluating nurse-led
follow-up, which makes it difficult to compare the studies. Several of the
studies used QoL as an outcome measure; this is a broad concept that includes
several aspects ranging from social role and psychosocial issues to symptoms and
therefore difficult to use as an outcome measure. Only two of the studies made
any cost-effective analyses, and the results are hard to interpret. CONCLUSIONS:
Nurse-led follow-up can potentially result in better continuity of care and the
availability of more time to provide psychosocial support and address patients'
information needs. However, more well-conducted research is needed before
equivalence to physician-led follow-up can be assessed in terms of survival,
recurrence, patient well-being and cost-effectiveness. RELEVANCE TO CLINICAL
PRACTICE: Results from well-conducted evaluation studies of nurse-led services
based on theory are needed so that relevant interventions can be implemented in
clinical practice. There is a need to in future studies include cost
effectiveness analyses to compare nurse-led services with other types of follow
up.
PMID- 27487479
TI - Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in
Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A
Randomized Clinical Trial.
AB - IMPORTANCE: Although numerous children receive methylphenidate hydrochloride for
the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known
about age-dependent and possibly lasting effects of methylphenidate on the human
dopaminergic system. OBJECTIVES: To determine whether the effects of
methylphenidate on the dopaminergic system are modified by age and to test the
hypothesis that methylphenidate treatment of young but not adult patients with
ADHD induces lasting effects on the cerebral blood flow response to dopamine
challenge, a noninvasive probe for dopamine function. DESIGN, SETTING, AND
PARTICIPANTS: A randomized, double-blind, placebo-controlled trial (Effects of
Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral
centers in the greater Amsterdam area in the Netherlands between June 1, 2011,
and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12
years or 23 to 40 years, and stimulant treatment-naive status. INTERVENTIONS:
Treatment with either methylphenidate or a matched placebo for 16 weeks. MAIN
OUTCOMES AND MEASURES: Change in the cerebral blood flow response to an acute
challenge with methylphenidate, noninvasively assessed using pharmacological
magnetic resonance imaging, between baseline and 1 week after treatment. Data
were analyzed using intent-to-treat analyses. RESULTS: Among 131 individuals
screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50
participants were randomized to receive methylphenidate and 49 to placebo.
Sixteen weeks of methylphenidate treatment increased the cerebral blood flow
response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI,
0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in
the placebo group. In the striatum, the methylphenidate condition differed
significantly from placebo in children but not in adults (mean difference, 7.7;
95% CI, 0.7-14.8; P = .03). CONCLUSIONS AND RELEVANCE: We confirm preclinical
data and demonstrate age-dependent effects of methylphenidate treatment on human
extracellular dopamine striatal-thalamic circuitry. Given its societal relevance,
these data warrant replication in larger groups with longer follow-up. TRIAL
REGISTRATION: identifier: NL34509.000.10 and trialregister.nl identifier:
NTR3103.
PMID- 27487480
TI - In vitro and in vivo effects of morin on the intestinal absorption and
pharmacokinetics of olmesartan medoxomil solid dispersions.
AB - PURPOSE: In-situ evaluation to corroborate morin effects on the intestinal
absorption and pharmacokinetic behavior of freeze-dried OLM-loaded solid
dispersions with Caco-2 and in-vivo studies Methods: Intestinal transport and
absorption studies were examined by Caco-2 permeability, in-situ single pass
perfusion and closed-loop models along with in-vivo pharmacokinetic studies to
evaluate and confirm the effect of P-gp-mediated activity of morin. We evaluated
the intestinal membrane damage in the presence of morin by measuring the release
of protein and lactate dehydrogenase (LDH) followed by using qualitative and
quantitative morphometric analysis to describe the surface characteristics of
intestinal epithelium. RESULTS: Morin showed the highest Peff value 13.8 +/- 0.34
* 10-6 cm/s in jejunum than ileum (p < .01) at 100 uM with absorption enhancement
of 1.31-fold together with enhanced (p < .01) secretory transport of 6.27 +/-
0.27 * 10 -6 cm/s in Caco-2 monolayer cells. Our findings noticed 2.37 (in-situ);
2.39 (in-vivo) and 1.43 (in-situ); 1.36 (in-vivo) fold increase in AUC0-t with
elevated Cmax and shortened Tmax for freeze-dried solid dispersion in the
presence of morin as compared to pure OLM and freeze-dried solid dispersions
without morin, respectively. CONCLUSIONS: Our study demonstrated that increased
solubilization through freeze-dried OLM-loaded solid dispersion together with
efflux inhibition improved intestinal permeability to one system that might lead
to novel solubilization and efflux pump inhibition as a novel alternative
potential to increase oral absorption and bioavailability of OLM.
PMID- 27487482
TI - Crystal Structure of the Apicoplast DNA Polymerase from Plasmodium falciparum:
The First Look at a Plastidic A-Family DNA Polymerase.
AB - Plasmodium falciparum, the primary cause of malaria, contains a non
photosynthetic plastid called the apicoplast. The apicoplast exists in most
members of the phylum Apicomplexa and has its own genome along with organelle
specific enzymes for its replication. The only DNA polymerase found in the
apicoplast (apPOL) was putatively acquired through horizontal gene transfer from
a bacteriophage and is classified as an atypical A-family polymerase. Here, we
present its crystal structure at a resolution of 2.9A. P. falciparum apPOL, the
first structural representative of a plastidic A-family polymerase, diverges from
typical A-family members in two of three previously identified signature motifs
and in a region not implicated by sequence. Moreover, apPOL has an additional N
terminal subdomain, the absence of which severely diminishes its 3' to 5'
exonuclease activity. A compound known to be toxic to Plasmodium is a potent
inhibitor of apPOL, suggesting that apPOL is a viable drug target. The structure
provides new insights into the structural diversity of A-family polymerases and
may facilitate structurally guided antimalarial drug design.
PMID- 27487481
TI - Molecular Mechanisms of Innate Immune Inhibition by Non-Segmented Negative-Sense
RNA Viruses.
AB - The host innate immune system serves as the first line of defense against viral
infections. Germline-encoded pattern recognition receptors detect molecular
patterns associated with pathogens and activate innate immune responses. Of
particular relevance to viral infections are those pattern recognition receptors
that activate type I interferon responses, which establish an antiviral state.
The order Mononegavirales is composed of viruses that possess single-stranded,
non-segmented negative-sense (NNS) RNA genomes and are important human pathogens
that consistently antagonize signaling related to type I interferon responses.
NNS viruses have limited encoding capacity compared to many DNA viruses, and as a
likely consequence, most open reading frames encode multifunctional viral
proteins that interact with host factors in order to evade host cell defenses
while promoting viral replication. In this review, we will discuss the molecular
mechanisms of innate immune evasion by select NNS viruses. A greater
understanding of these interactions will be critical in facilitating the
development of effective therapeutics and viral countermeasures.
PMID- 27487483
TI - Phosphoinositide Binding Inhibits Actin Crosslinking and Polymerization by
Palladin.
AB - Actin cytoskeleton remodeling requires the coordinated action of a large number
of actin binding proteins that reorganize the actin cytoskeleton by promoting
polymerization, stabilizing filaments, causing branching, or crosslinking
filaments. Palladin is a key cytoskeletal actin binding protein whose normal
function is to enable cell motility during development of tissues and organs of
the embryo and in wound healing, but palladin is also responsible for regulating
the ability of cancer cells to become invasive and metastatic. The membrane
phosphoinositide phosphatidylinositol (PI) 4,5-bisphosphate [PI(4,5)P2] is a well
known precursor for intracellular signaling and a bona fide regulator of actin
cytoskeleton reorganization. Our results show that two palladin domains
[immunoglobulin (Ig) 3 and 34] interact with the head group of PI(4,5)P2 with
moderate affinity (apparent Kd=17MUM). Interactions with PI(4,5)P2 decrease the
actin polymerizing activity of Ig domain 3 of palladin (Palld-Ig3). Furthermore,
NMR titration and docking studies show that residues K38 and K51, which are
present on the beta-sheet C and D, form salt bridges with the head group of
PI(4,5)P2. Moreover, charge neutralization at lysine 38 in the Palld-Ig3 domain
severely limits the actin polymerizing and bundling activity of Palld-Ig3. Our
results provide biochemical proof that PI(4,5)P2 functions as a moderator of
palladin activity and have also identified residues directly involved in the
crosslinking activity of palladin.
PMID- 27487484
TI - A Vesicle Supra-Assembly Approach to Synthesize Amine-Functionalized Hollow
Dendritic Mesoporous Silica Nanospheres for Protein Delivery.
AB - Intracellular delivery of proteins is a promising strategy of intervention in
disease, which relies heavily on the development of efficient delivery platforms
due to the cell membrane impermeability of native proteins, particularly for
negatively charged large proteins. This work reports a vesicle supra-assembly
approach to synthesize novel amine-functionalized hollow dendritic mesoporous
silica nanospheres (A-HDMSN). An amine silica source is introduced into a water
oil reaction solution prior to the addition of conventional silica source
tetraethylorthosilicate. This strategy favors the formation of composite vesicles
as the building blocks which further assemble into the final product. The
obtained A-HDMSN have a cavity core of ~170 nm, large dendritic mesopores of 20.7
nm in the shell and high pore volume of 2.67 cm3 g-1 . Compared to the calcined
counterpart without amine groups (C-HDMSN), A-HDMSN possess enhanced loading
capacity to large negative proteins (IgG and beta-galactosidase) and improved
cellular uptake performance, contributed by the cationic groups. A-HDMSN enhance
the intracellular uptake of beta-galactosidase by up to 5-fold and 40-fold
compared to C-HDMSN and free beta-galactosidase, respectively. The active form of
beta-galactosidase delivered by A-HDMSN retains its intracellular catalytic
functions.
PMID- 27487485
TI - Indocyanine Green Lymphographic Evidence of Surgical Efficacy Following
Microsurgical and Supermicrosurgical Lymphedema Reconstructions.
AB - Background Microsurgical vascularized lymph node transfer (VLNT) and
supermicrosurgical lymphaticovenular anastomosis (LVA) are increasingly performed
to treat lymphedema. The surgical outcome is commonly assessed by volume-based
measurement (VBM), a method that is not consistently reliable. We describe
indocyanine green (ICG) lymphography as an alternative postoperative tracking
modality after lymphatic reconstruction with VLNT and LVA. Methods VLNT and LVA
were performed in patients with therapy-refractory lymphedema. Patients were
evaluated qualitatively by clinical assessment, quantitatively with VBM, and
lymphographically using ICG lymphography. The evaluation was performed
preoperatively, and at 3, 6, and 12-month postoperatively. Results Overall, 21
patients underwent lymphatic reconstruction with either VLNT or LVA. All reported
prompt and durable relief of symptoms during the study period. All experienced
disease regression based on the Campisi criteria. Out of the 21 patients, 20
(95%) demonstrated lymphographic down staging of disease severity. Out of the 21
patients, 3 (14%) developed a paradoxical increase in limb volume based on VBM
despite clinical improvement. Conclusions ICG lymphography correlated highly with
patient self-assessment and clinical examination, and is an effective
postoperative tracking modality after lymphatic reconstruction.
PMID- 27487487
TI - Hormonally active agents in the environment: a state-of-the-art review.
AB - After the Second World War, infatuation with modern products has exponentially
widened the spectrum of chemicals used. Some of them are capable of hijacking the
endocrine system by blocking or imitating a hormone and are referred to as
hormonally active chemicals or endocrine disruptors. These are chemicals that the
body was not designed for evolutionarily and they are present in every matrix of
the environment. We are living in a chemical world where the exposures are
ubiquitous and take place in combinations that can interact with the endocrine
system and some other metabolic activities in unexpected ways. The complexity of
interaction of these compounds can be understood by the fact that they interfere
with gene expression at extremely low levels, consequently harming an individual
life form, its offspring or population. As the endocrine system plays a critical
role in many biological or physiological functions, by interfering body's
endocrine system, endocrine disrupting compounds (EDCs) have various adverse
effects on human health, starting from birth defects to developmental disorders,
deadly deseases like cancer and even immunological disorders. Most of these
compounds have not been tested yet for safety and their effects cannot be
assessed by the available techniques. The establishment of proper exposure
measurement techniques and integrating correlation is yet to be achieved to
completely understand the impacts at various levels of the endocrine axis.
PMID- 27487486
TI - Calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer
stromal interactions in a mouse xenograft model.
AB - Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However,
recent clinical trials testing several antifibrotic agents on pancreatic cancer
have not shown clear efficacy. Therefore, further investigation of desmoplasia
targeting antifibrotic agents by another mechanism is needed. Calpeptin, an
inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In
this study, we investigated the anticancer effects of calpeptin on pancreatic
cancer. We investigated whether calpeptin inhibited tumor progression using a
mouse xenograft model. We used quantitative RT-PCR to evaluate the expression of
calpain-1 and calpain-2 mRNA in pancreatic cancer cells (PCCs) and pancreatic
stellate cells (PSCs). We also undertook functional assays, including
proliferation, migration, and invasion, to evaluate the inhibitory effects of
calpeptin on PCCs and PSCs. Quantitative RT-PCR indicated that PCCs and PSCs
expressed calpain-2 mRNA. Calpeptin reduced tumor volume (P = 0.0473) and tumor
weight (P = 0.0471) and inhibited the tumor desmoplastic reaction (P < 0.001) in
xenograft tumors in nude mice. Calpeptin also inhibited the biologic functions of
PCCs and PSCs including proliferation (P = 0.017), migration (P = 0.027), and
invasion (P = 0.035) in vitro. Furthermore, calpeptin reduced the migration of
PCCs and PSCs by disrupting the cancer-stromal interaction (P = 0.0002). Our
findings indicate that calpeptin is a promising antitumor agent for pancreatic
cancer, due not only to its suppressive effect on PCCs and PSCs but also its
disruption of the cancer-stromal interaction.
PMID- 27487488
TI - Prevalence and awareness of functional and structural foot abnormalities in
children and adolescents with type 1 diabetes.
AB - BACKGROUND: The ISPAD guideline 2011/2014 advises annual podiatric screening to
detect foot complications and identify other possible risk factors such as
functional and structural foot abnormalities. The aim of this study was to assess
the prevalence and awareness of neurovascular, functional and structural foot
abnormalities in children and adolescents with type 1 diabetes mellitus (T1DM).
METHODS: All patients aged 0-18 years with T1DM were invited for a foot
examination and structured questionnaire by a certified podiatrist. RESULTS:
Three of the examined patients (n=128) showed signs of possible long-term
complications. Structural and functional foot problems were observed in 71.9%
(n=92). Of all patients, 38.3% (n=49) required further treatment by a podiatrist.
CONCLUSIONS: Functional and structural foot abnormalities are a frequent problem
in children with T1DM in the southern part of the Netherlands. These
abnormalities are an additional risk factor for developing long-term foot
complications. Education in and implementation of the guideline are necessary.
PMID- 27487489
TI - Novel homozygous likely-pathogenic intronic variant in INS causing permanent
neonatal diabetes in siblings.
AB - Permanent neonatal diabetes (PNDM) is a rare genetic condition characterized by
hyperglycemia, insulinopenia, and failure to thrive beginning in the first 6
months of life. Recessive mutations in INS lead to decreased production of
insulin via a variety of mechanisms. We present a case of two brothers, born to
consanguineous parents, with a novel homozygous intronic variant in the INS gene.
Each patient presented with intrauterine growth restriction (IUGR) and
significant hyperglycemia within the first 24 h of life. All the grandparents
have a diagnosis of diabetes, one of them requiring insulin treatment and the
parents currently deny personal histories of diabetes. Although this mutation has
not previously been described, given the segregation of the mutation, absence of
heterozygosity (AOH) in the genomic region encompassing the INS locus, documented
insulinopenia, and high neonatal insulin requirements, we suspect that this
variant is pathogenic. Possible implications for personalized treatment of the
underlying molecular etiology for an individual's diabetes are discussed.
PMID- 27487490
TI - Tanshinones and mental diseases: from chemistry to medicine.
AB - The prevalence of mental diseases, especially neurodegenerative disorders, is
ever-increasing, while treatment options for such disorders are limited and
insufficient. In this scarcity of available medication, it is a feasible strategy
to search for potential drugs among natural compounds, such as those found in
plants. One such plant source is the root of Chinese sage, Salvia miltiorrhiza
Bunge (Labiatae), which contains several compounds reported to possess
neuroprotective activities. The most important of these compounds are
tanshinones, which have been reported to possess ameliorative activity against a
myriad of mental diseases such as Alzheimer's disease, cerebral
ischemia/reperfusion injury, and glioma, along with promoting neuronal
differentiation and manifesting antinociceptive and anticonvulsant outcomes. This
review offers a critical evaluation of the utility of tanshinones to treat mental
illnesses, and sheds light on the underlying mechanisms through which these
naturally occurring compounds confer neuroprotection.
PMID- 27487491
TI - Correlative study of peripheral ATP1A1 gene expression level to anxiety severity
score on major depressive disorder patients.
AB - BACKGROUND: Major depressive disorder (MDD) frequently co-occurs with other
psychiatric problems. Our previous study showed that ATP1A1 gene expression level
was significantly decreased in MDD patients. This research explores the potential
correlations between the ATP1A1 expression level reduction and MDD patients'
clinical manifestation. METHODS: All participant patients were diagnosed by
Diagnostic and Statistical Manual of Mental Disorders - 4th edition (DSM-IV).
Hamilton rating scale for depression (HAM-D) and anxiety (HAM-A) were applied to
group patients into different categories. ATP1A1 expression level was measured by
reverse transcript real-time polymerase chain reaction. RESULTS: ATP1A1
expression levels of all MDD subgroups showed significant reduction compared to
the control group (p<0.01). Further, the trend of ATP1A1 expression level
reduction is significantly related to MDD patients' HAM-A scores (p<0.01).
However, there was no significance between ATP1A1 level and HAM-D scores
(p>0.05). CONCLUSIONS: ATP1A1 expression level reduction is related to MDD
anxiety score, which may be an explanation for the clinical manifestations and
the underlining physiological mechanisms.
PMID- 27487492
TI - Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents
gabapentin, lamotrigine and topiramate in patients undergoing major surgeries at
a tertiary care hospital: a randomized double blind clinical trial.
AB - BACKGROUND: Surgical injury leads to postoperative pain hypersensitivity preceded
by central nervous sensitization, due to lowered pain threshold in peripheral
nociceptors and increased excitability of the spinal neurons. Pre-emptive
analgesia is intended to decrease pain perception and overall analgesic need by
use of drug regimen seizing central nervous system sensitization before exposure
to painful stimuli. Earlier, few studies support pre-emptive analgesic efficacy
of novel antiepileptic agent gabapentin. But topiramate and lamotrigine though
proven analgesic in animal models of chronic pain and clinical studies of
gabapentin resistant neuropathic pain; literature search revealed scarce data on
its pre-emptive analgesic efficacy. The present study is designed to study and
compare the pre-emptive analgesic efficacy of lamotrigine, topiramate and
gabapentin (as control) in postoperative pain control. METHODS: This randomized
clinical trial included 90 patients of either sex, between 18 and 70 years
undergoing major surgeries. Patients were randomly allocated into control and
test groups and received respective treatment 30 min before induction of
anesthesia. Aldrete's score and pain score were recorded using visual analogue
scale and facial and behavioral rating scales at awakening and at 1, 2, 4, 6 and
24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Data were
analyzed using OpenEpi and SciStatCalc statistical softwares. RESULTS:
Significantly higher pain scores were observed in the topiramate group
postoperatively for 2 h on all pain scales (p<0.05). Lamotrigine-treated patients
were more comfortable throughout the study with significantly less (p<0.05)
postoperative analgesic requirement comparable to gabapentin. CONCLUSIONS: Study
results are strongly suggestive of pre-emptive analgesic efficacy of single oral
dose lamotrigine comparable to gabapentin and superior to topiramate in
postoperative pain control.
PMID- 27487493
TI - Anti-inflammatory, anti-diarrheal, thrombolytic and cytotoxic activities of an
ornamental medicinal plant: Persicaria orientalis.
AB - BACKGROUND: Persicaria orientalis, an ornamental medicinal plant, has been used
in traditional medicine for the treatment of various diseases. Although the plant
is reported to have some important pharmacological effects, many medicinal values
remain unidentified. Our objective was to evaluate the anti-inflammatory, anti
diarrheal, thrombolytic, and cytotoxic properties of the methanol extract of P.
orientalis leaves (Po-MeOH). METHODS: Anti-inflammatory activity was measured by
the inhibition of hypotonicity-induced human red blood cell hemolysis and albumin
denaturation technique in vitro of Po-MeOH. Diarrheal episodes were examined in
mice with castor oil-induced diarrhea. The clot lysis and brine shrimp lethality
bioassay in vitro were used to evaluate the thrombolytic and cytotoxic activities
of the plant extract, respectively. RESULTS: Using in vitro anti-inflammatory
models, the results demonstrated that Po-MeOH at the five different dose ranges
from 31.25 to 500 MUg/mL significantly (p<0.05) protected (0.98%-50.71%) the
erythrocyte membrane against lysis induced by hypotonic medium solution and
protein denaturation (38.27%-79.22%) of bovine albumin, respectively. The extract
exhibited a significant reduction of severity (75.17%) of castor oil-induced
diarrhea in mice at the highest dose of 400 mg/kg compared to loperamide (82.06%)
at 5 mg/kg. Po-MeOH also showed 33.14% clot lytic activity in the thrombolytic
test and cytotoxicity with LC50 value 58.91 MUg/mL in the brine shrimp bioassay.
CONCLUSIONS: These findings suggest that Po-MeOH has significant anti
inflammatory and anti-diarrheal effects along with moderate thrombolytic and
lower cytotoxic properties that may warrant the further exploration.
PMID- 27487494
TI - Genetic modification of tomato with the tobacco lycopene beta-cyclase gene
produces high beta-carotene and lycopene fruit.
AB - Transgenic Solanum lycopersicum plants expressing an additional copy of the
lycopene beta-cyclase gene (LCYB) from Nicotiana tabacum, under the control of
the Arabidopsis polyubiquitin promoter (UBQ3), have been generated. Expression of
LCYB was increased some 10-fold in ripening fruit compared to vegetative tissues.
The ripe fruit showed an orange pigmentation, due to increased levels (up to 5
fold) of beta-carotene, with negligible changes to other carotenoids, including
lycopene. Phenotypic changes in carotenoids were found in vegetative tissues, but
levels of biosynthetically related isoprenoids such as tocopherols, ubiquinone
and plastoquinone were barely altered. Transformants showed tolerance to the
bleaching herbicide beta-cyclase inhibitor, 2-(4-chlorophenylthio) triethylamine.
The phenotype was inherited for at least three generations.
PMID- 27487495
TI - Commutability of proficiency testing material containing tobramycin: a study
within the framework of the Dutch Calibration 2.000 project.
AB - BACKGROUND: Results from external quality assessment schemes (EQASs) can provide
information about accuracy and comparability of different measurement methods,
provided that the material used in these schemes behave identical to patient
samples among the different methods, a characteristic also known as
commutability. The aim of this study was to assess the commutability of different
matrices for the material used in an EQAS for tobramycin. METHODS: Proficiency
testing material (PTM) and patient samples containing tobramycin were prepared,
collected, pooled, and distributed to participating laboratories for analysis.
Low, medium, and high tobramycin concentrations in liquid human, liquid bovine
and lyophilized bovine serum were tested in this study. The patient serum results
of every laboratory were plotted against each of the other laboratories, and the
distances of the PTM results to the patient serum regression line were
calculated. For comparison, these distances were divided by the average within
laboratory standard deviation (SDwl) of the results reported in the official EQAS
for tobramycin, resulting in a relative residual. The commutability decision
limit was set at 3 SDwl. RESULTS: With 10 laboratories participating in this
study, 45 laboratory couples were formed. For human serum, only one relative
residual for high concentrations of tobramycin was found outside the
commutability decision limit. For liquid and lyophilized bovine sera, the number
of relative residuals outside the decision limit was between 15 and 18 for low,
medium, and high tobramycin concentrations. CONCLUSIONS: The PTM used for
tobramycin is preferably prepared with human serum.
PMID- 27487496
TI - Detection of gastric Helicobacter spp. in stool samples of dogs with gastritis.
AB - The aim of this study was to determine the prevalence and identify the species of
gastric Helicobacter in the stool of dogs with gastritis. The study was carried
out on thirty dogs of different breeds, of both genders and of various ages,
diagnosed with gastritis. Helicobacter spp. was detected in stool samples using
the nested-PCR method. Helicobacter bacteria were identified in stool samples
from seven (23.3%) dogs. Helicobacter heilmannii was found to be the most common
species of gastric Helicobacter. Helicobacter salomonis was identified much less
frequently, while Helicobacter felis, Helicobacter pylori and Helicobacter
bizzozeronii were not detected in any of the samples.
PMID- 27487497
TI - Effects of boldenone undecylenate on growth performance, maintenance behaviour,
reproductive hormones and carcass traits of growing rabbits.
AB - The present study was done to evaluate the effect of boldenone undecylenate (BOL)
on growth performance, maintenance behaviour, reproductive hormones and carcass
traits of male rabbits. Sixty apparently healthy New Zealand White male rabbits,
5 weeks of age, were allotted to 3 equal groups. Each group was subdivided into 5
replicates, where the first group is control. The second group (B1) comprised
rabbits that received 2 intramuscular injections of BOL (5 mg/kg) with 3 week
intervals (9 and 12 weeks of age), while the third group (B2) included rabbits
that received 3 intramuscular injections of BOL (5 mg/kg) with 2 week intervals
(8, 10 and 12 weeks of age). The end of the trial was after 4 weeks from the last
injection (16 weeks of age). The results revealed that the treated groups had a
significant increase in total body weight, daily gain and feed efficiency, with a
significant decrease in feed conversion ratio (FCR). Ingestive, locomotion and
grooming behaviors were significantly higher in treated groups. Lateral pasture
and exploratory behaviors were significantly higher in the control group.
Administration of BOL resulted in a significant increase in dressing % and a
significant decrease in testes %. Groups treated with BOL had a significantly
(P<0.05) decreased serum testosterone level, simultaneously with a significantly
increased estradiol level. The results indicate that BOL improves performance and
carcass traits. Furthermore, there are hormonal-behavioral correlations through
enhancement of ingestive and locomotion behaviors of treated animals.
PMID- 27487498
TI - Tumor necrosis factor-alpha alters integrins and metalloprotease ADAM12 levels
and signaling in differentiating myoblasts.
AB - The extracellular matrix (ECM) is important in the regulation of myogenesis. We
hypothesized that tumor necrosis factor-alpha (TNF-alpha) modifies ECM during
differentiation of mouse C2C12 myoblasts. Exogenous TNF-alpha (1 ng/ml)
stimulated myoblast fusion on the 3rd day (by 160% vs control) but not on the 5th
day of myogenesis. The level of integrin alpha5 was significantly augmented by
TNF-alpha during 5 day-differentiation; however, integrin beta1 was higher than
control only on the 3rd day of cytokine treatment. Both the abundance of integrin
alpha5 bound to actin and the level of integrin beta1 complexed with integrin
alpha5 increased in the presence of TNF-alpha, especially on the 3rd day of
differentiation. Similarly, the stimulatory effects of TNF-alpha on integrin
alpha3, metalloprotease ADAM12 and kinases related to integrins, FAK and ILK,
were limited to the 3rd day of differentiation. We concluded that TNF-alpha
induced changes in ECM components in differentiating myogenic cells, i.e. i)
increased expression of integrin alpha5, beta1, alpha3, and metalloprotease
ADAM12, ii) enhanced formation of alpha5beta1 integrin receptors and interaction
of integrin alpha5-cytoskeleton, and iii) increased expression of kinases
associated with integrin signaling, FAK and ILK, were temporarily associated with
the onset of myocyte fusion.
PMID- 27487499
TI - The relationship between basal and luminal cytokeratins with histopathologic
characteristics of canine mammary gland cancer.
AB - Neoplasia occurs mostly in mammary glands in female dogs and mammary gland cancer
is one of the causes of death in these animals cytokeratins are one of the most
important of tumor markers for identification of tumor prognosis. In this study,
120 canine malignant tumor samples of mammary glands were studied. From each
sample, a section was taken for hematoxylin-eosin staining and two sections for
immunohistochemical staining of markers CK5/6 and CK7. Histopathology slides was
evaluated by light microscope. The results show that the presence of markers CK7
and CK5/6 had no significant relationship with tumor grade and type (p<0.05).
However, it seems that unlike humans, CK5/6 and CK7 is not an independent
prognostic factor in canine mammary gland tumors.
PMID- 27487500
TI - Production and characterization of egg yolk antibody (IgY) against recombinant
VP8-S2 antigen.
AB - Bovine Rotavirus and Bovine Coronavirus are the most important causes of diarrhea
in newborn calves and in some other species such as pigs and sheep. VP8 subunit
of rotavirus is the major determinant of the viral infectivity and
neutralization. Spike glycoprotein of coronavirus is responsible for induction of
neutralizing antibody response. Studies showed that immunoglobulin of egg yolk
(IgY) from immunized hens has been identified to be a convenient source for
specific antibodies for using in immunotherapy and immunodiagnostic to limit the
infections. In this study, chimeric VP8-S2 gene was designed using by
computational techniques. The chimeric VP8-S2 gene was cloned and sub-cloned into
pGH and pET32a (+) vectors. Then, recombinant pET32a-VP8-S2 vector was
transferred into E. coli BL21 CodonPlus (DE3). The expressed protein was purified
by Ni-NTA chromatography column. Hens were immunized with the purified VP8-S2
protein three times. IgY was purified from egg yolks using polyethylene glycol
precipitation method. Activity and specificity of anti-VP8-S2 IgY were detected
by dot-blotting, Western-blotting and indirect ELISA. We obtained anti-VP8-S2 IgY
by immunizing hens with the recombinant VP8-S2 protein. The anti-VP8-S2 IgY was
showed to bind specifically to the chimeric VP8-S2 protein by dot-blotting,
Western-blotting analyses and indirect ELISA. The result of this study indicated
that such construction can be useful to investigate as candidates for development
of detection methods for simultaneous diagnosis of both infections. Specific IgY
against the recombinant VP8-S2 could be recommended as a candidate for passive
immunization against bovine rotavirus and bovine coronavirus.
PMID- 27487501
TI - Identification of point mutations in exon 2 of GDF9 gene in Kermani sheep.
AB - Screening the fertile ewes from national herds to detect the major genes for
prolificacy is an effective way to create the fertile flocks. Growth
differentiation factor (GDF) 9 is a member of the transforming growth factor beta
superfamily that is essential for folliculogenesis and female fertility. The aim
of this study was to detect single nucleotide polymorphisms (SNPs) in exon 2 of
GDF9 gene in Kermani sheep breed using PCR-SSCP. Genomic DNA was extracted from
whole blood of collected samples using salting-out method. Whole exon 2 of GDF9
gene was amplified (634 bp and 647 bp fragments) using designed specific primers.
The single stranded conformation polymorphism (SSCP) patterns of PCR products
were studied using electrophoresis on acrylamide gel and silver-nitrate staining
method. Finally, 4 banding patterns for the first primer pair and 4 banding
patterns for the second primer pair were obtained. Also, indices of population
genetic per SNP were calculated using Gen Alex 6.41 software. The sequencing
results showed the presence of 3 mutations (SNP) (443, 477 and 721 positions) in
the studied population.
PMID- 27487502
TI - Lawsonia intracellularis and Porcine Circovirus type-2 infection in Estonia.
AB - The present study describes the reasons of post-weaning distress in Estonian pig
herds. Here we examined the natural cases of Lawsonia intracellularis and porcine
circovirus 2 (PCV2) infection and co-infections. The presence of L.
intracellularis in swine herds were tested by PCR and by histopathological
methods, whereas PCV2 was detected by real-time-PCR and immunohistochemical
stainings. Seven of the 11 investigated herds with signs of post-weaning wasting
were infected with L. intracellularis and all 11 herds with PCV2. From the
analysed samples 22.2% were infected with L. intracellularis and 25% with PCV2.
The results of microbiological studies suggested that the piglets suffered from
enteritis and pneumonia. Escherichia coli and Pasteurella multocida often
aggravated the process of illness. The frequency of L. intracellularis was high
in pigs 7-12 weeks old (18.5-42.7%) and PCV2 infection was too high in pigs 7-12
weeks old (24.8-32.7%). E. coli was often a co-factor with L. intracellularis and
PCV2. The primary reasons of post weaning wasting were PCV2 and E. coli, later
aggravated by L. intracellularis and other pathogens. Our results indicated that
different pathogens have an important role in developing post-weaning wasting.
Proliferative intestinal inflammation caused by L. intracellularis is mainly
characterised by its localization and morphological findings. The main gross
lesions were the enlargement of mesenteric lymph nodes and thickening of the wall
of ileum. In post-weaning multi-systemic wasting syndrome there are
characteristic histological lesions in lymphoid tissues. They consist of a
variable degree of lymphocyte depletion, together with histiocytic and/or
multinucleate giant cell infiltration. This basic lymphoid lesions is observable
in almost all tissues of a single severely affected animal, including lymph
nodes, Peyer's patches and spleen. Sporadically, multifocal coagulative necrosis
may be observed.
PMID- 27487503
TI - Differential expression of Toll-like receptor 4 signaling pathway genes in
Escherichia coli F18-resistant and - sensitive Meishan piglets.
AB - The Toll-like receptor 4 (TLR4) signaling pathway is an important inflammatory
pathways associated with the progression of numerous diseases. The aim of the
present study was to investigate the relationship between TLR4 signaling and
resistance to Escherichia coli F18 in locally weaned Meishan piglets. Using a
real-time PCR approach, expression profiles were determined for key TLR4
signaling pathway genes TLR4, MyD88, CD14, IFN-alpha, IL-1beta and TNF-alpha in
the spleen, thymus, lymph nodes, duodenum and jejunum of E. coli F18-resistant
and -sensitive animals. TLR4 signaling pathway genes were expressed in all the
immune organs and intestinal tissues, and the expression was generally higher in
the spleen and lymph nodes. TLR4 transcription was higher in the spleen of
sensitive piglets (p<0.05), but there was no significant difference in TLR4 mRNA
levels in other tissues. Similarly, CD14 transcription was higher in lymph nodes
of sensitive animals (p<0.05) but not in other tissues. IL-1beta expression was
higher in the spleen and in the duodenum of resistant piglets (p<0.05, p<0.01,
respectively), and there were no significant differences in other tissues. There
were also no significant differences in the expression of MyD88, TNF-alpha and
IFN-alpha between sensitive and resistant piglets (p>0.05). These results further
confirm the involvement of the TLR4 signaling pathway in resistance to E. coli
F18 in Meishan weaned piglets. The resistance appeared to be mediated via
downregulation of TLR4 and CD14, and upregulation of MyD88 that may promote the
release of cytokines TNF-alpha, IL-1beta, IFN-alpha and other inflammatory
mediators which help to fight against E. coli F18 infection.
PMID- 27487505
TI - Modeling the effect of temperature on survival rate of Listeria monocytogenes in
yogurt.
AB - The aim of the study was to (i) evaluate the behavior of Listeria monocytogenes
in a commercially produced yogurt, (ii) determine the survival/inactivation rates
of L. monocytogenes during cold storage of yogurt and (iii) to generate primary
and secondary mathematical models to predict the behavior of these bacteria
during storage at different temperatures. The samples of yogurt were inoculated
with the mixture of three L. monocytogenes strains and stored at 3, 6, 9, 12 and
15 degrees C for 16 days. The number of listeriae was determined after 0, 1, 2,
3, 5, 7, 9, 12, 14 and 16 days of storage. From each sample a series of decimal
dilutions were prepared and plated onto ALOA agar (agar for Listeria according to
Ottaviani and Agosti). It was found that applied temperature and storage time
significantly influenced the survival rate of listeriae (p<0.01). The number of
L. monocytogenes in all the samples decreased linearly with storage time. The
slowest decrease in the number of the bacteria was found in the samples stored at
6 degrees C (D-10 value = 243.9 h), whereas the highest reduction in the number
of the bacteria was observed in the samples stored at 15 degrees C (D-10 value =
87.0 h). The number of L. monocytogenes was correlated with the pH value of the
samples (p<0.01). The natural logarithm of the mean survival/inactivation rates
of L. monocytogenes calculated from the primary model was fitted to two secondary
models, namely linear and polynomial. Mathematical equations obtained from both
secondary models can be applied as a tool for the prediction of the
survival/inactivation rate of L. monocytogenes in yogurt stored under temperature
range from 3 to 15 degrees C, however, the polynomial model gave a better fit to
the experimental data.
PMID- 27487504
TI - Microbiological and parasitological survey of zoonotic agents in apparently
healthy feral pigeons.
AB - Microbiological and parasitological investigation was carried out on a colony of
feral pigeons, located in a green area near the main hospital of a Central Italy
city. One hundred pigeons were submitted to clinical examination. Cloacal swabs,
grouped in pool of 4 samples, were analyzed to detect the presence of Coxiella
burnetii, Chlamydia psittaci, Chlamydophila spp. using a biomolecular procedure,
while individual cloacal samples were examined for Salmonella spp., Campylobacter
spp., and yeasts by means of a specific culture media. An ELISA test was used to
determine the presence of Giardia spp., and Cryptosporidium spp. coproantigens.
Individual serological samples were also tested with the modified agglutination
test (MAT) in order to detect antibodies against Toxoplasma gondii. The pigeons
did not show any clinical signs. The cloacal pools proved to be negative for C.
burnetii DNA while three pools were positive for C. psittaci or Chlamydophila
spp. DNAs. Salmonella spp. was not detected. C. jejuni and C. coli were found in
13% and 4% of the samples, respectively. No Giardia spp. and Cryptosporidium spp.
were detected. Thirty-three out of 100 samples (33%) were positive for yeast
colonies. The seroprevalence for T. gondii was 8%. Although with moderate
incidence, potentially zoonotic agents were present thus highlighting the need
for sanitary surveillance on feral pigeon colonies.
PMID- 27487506
TI - Morphology of immune organs after very virulent plus strain of Marek's disease
virus infection in vaccinated hens.
AB - Marek's disease (MD) outbreaks in poultry flocks may be associated with
overriding of vaccine immune protection by very virulent (vvMDV) or very virulent
plus (vv+MDV) strains. This paper presents the study on lymphoid organ morphology
in the latent phase of MD caused by vv+MDV which break post-vaccinal protection
in hens. We also immunohistochemically examined B and T populations as well as
B/T and CD4+/CD8+ ratio of lymphocytes in lymphatic organs and, as a background,
in MD lymphomas from non-lymphatic organs. The number of antigen expressed cells
was evaluated as a percentage of positive cells in the one power field. Organ
samples were collected from 24 dead reproductive hens (Ross 308 line) in age
between 35-56 weeks, infected with vv+MDV. The hens originated from farms with MD
outbreaks, despite earlier routine vaccination with CVI988/Rispens + HVT. The
control organ samples originated from 15 clinically healthy hens at the same age
and line, subjected to the same vaccination schedule. The number of CD3+, CD8+
and TCRgammadelta+ cells was significantly lower in MDV infected thymus, spleen
and cecal tonsils in comparison to that found in the control organs. The
proportion of CD4+ was also distinctly reduced in the thymus and limited in the
spleen of MDV infected hens. This study revealed that infection with field vv+MDV
isolates might break post-vaccinal protection and influence the central and
peripheral immune system. The decrease in CD8+ and TCRgammadelta+ cell number in
the thymus, spleen and cecal tonsils suggests that primarily these cells are
involved in cell-mediated cytotoxicity against MDV transformed cells during
latency.
PMID- 27487507
TI - Safety of the long-term application of QuikClot Combat Gauze, ChitoGauze PRO and
Celox Gauze in a femoral artery injury model in swine - a preliminary study.
AB - The purpose of this study was to examine the safety of the long-term application
of QuikClot Combat Gauze, ChitoGauze PRO and Celox Gauze using a swine model. The
study was conducted on nine pigs weighing approximately 30 kg, which were
randomly divided into three groups. Under deep anesthesia, the pigs underwent
complete transverse cutting of the femoral artery in the groin region. Hemostatic
dressings were left in the wound for 24 hours. The animals were euthanized 24
hours after dressing application. In each group, macroscopic and microscopic
severe changes and shock symptoms were observed in the lungs, liver, kidneys and
heart. Fibrino-gaseous embolic material was found in the pulmonary artery of each
group and in the lung vessels of the animals from the ChitoGauze PRO and Celox
Gauze groups. In conclusion, the long-term application of the evaluated
hemostatic dressings has the risk of coagulopathy and reaching the progressive
stage of shock. The residues from the hemostatic dressings can ingress into the
systemic circulation, thereby increasing the risk of embolus formation. Because
of these harmful effects, the evaluated hemostatic dressings are not appropriate
for long-term use. Future studies are needed on the consequences of the long-term
application of these hemostatic agents.
PMID- 27487508
TI - Morphology and immunoreactivity of canine and feline extramedullary
plasmacytomas.
AB - The aim of the study was the evaluation of morphology and immunophenotype of
canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours,
located in skin, oral cavity and spleen were surgically excised, fixed and
processed for histopathology and immunohistochemistry (CD79alpha, CD18,
proliferating cell nuclear antigen, metallothionein). Histologically, tumours
were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin,
or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression
of CD79alpha antigen. The expression of CD18 was observed in canine cutaneous and
splenic tumours. In canine tumours expression of metallothionein was low to
moderate, while in feline plasmacytomas - absent or low. In canine tumours, the
mitotic index and proliferating cell nuclear antigen index were positively
correlated with the expression of metallothionein. In feline tumours no
correlation between mitotic index, proliferating cell nuclear antigen and
metallothionein was found. This is the first study describing expression of
metallothionein in canine and feline extramedullary plasmacytoma.
PMID- 27487509
TI - Occurence of Bordetella bronchiseptica in domestic cats with upper respiratory
tract infections.
AB - Bordetella bronchiseptica is a widespread Gram-negative pathogen occurring in
different mammal species. It is known to play a role in the etiology of
infectious atrophic rhinitis of swine, canine kennel cough, respiratory syndromes
of cats, rabbits and guinea pigs, and sporadic human cases have also been
reported. The aim of this article is to present the occurrence of infections
caused by these bacteria in domestic cats with respiratory symptoms, as well as
to conduct a molecular analysis of the flaA gene B. bronchiseptica for the
purpose of ascertaining whether cats become infected with one or more bacteria
strains. B. bronchiseptica was isolated from the respiratory system of 16 out of
35 domestic cats with symptoms of respiratory tract infections. Polymorphism
analysis of polymerase chain reaction products of B. bronchiseptica flaA was
performed to reveal the possible differences in nucleotide sequences of the
flagellin gene. The phylogenetic analysis of nucleotide sequences obtained during
PCR indicated that the isolates of bacteria from our own studies are
characterised by 100% homology of the analysed fragment of the flaA gene, which
suggests maintenance of a single genotype of these microorganisms in the cat
population. Moreover, the bacteria revealed full homology with reference strain
B. bronchiseptica ATCC 4617, and 99.4% homology with strain B. parapertussis ATCC
15311. This indicates that the PCR optimised for the Bordetella spp. flaA gene,
combined with sequencing of amplicons obtained in PCR, is an effective diagnostic
method allowing differentiation of Bordetella spp. type microorganisms.
PMID- 27487510
TI - Evaluation of bone marrow with particular consideration of the megakaryocyte
lineage and coagulation profile in the pregnant fallow deer (Dama dama).
AB - The aim of the study was to evaluate the megakaryocyte lineage of bone marrow and
coagulation parameters in fallow deer during the last month of pregnancy. The
animals were managed in the barn-feeding system. Twenty female fallow deer, aged
2-3 years, divided into 2 groups were used in the study. Group 1 comprised the
females in the last month of pregnancy, and the non-pregnant females were used as
the control. All the animals were clinically healthy. Coagulation parameters were
measured in all the deer: thrombin time (TT), prothrombin time (PT), activated
partial thromboplastin time (APTT), and plasma concentrations of fibrinogen, D
dimer, and antithrombin III. A quantitative assessment of bone marrow was carried
out for the erythroblastic, myeloid, lymphoid, monocyte-macrophage, and
megakaryopoietic cell lines. A detailed analysis of megakaryocyte lineage was
performed after whole blood and platelet count. There were no significant
differences in the erythroblast, granulocyte, monocyte-macrophage and lymphoid
systems between the animal groups. Thrombocyte count in the pregnant deer was
lower than that found in the control group. Bone marrow smears revealed a
slightly decreased megakaryocyte count, while the megakaryoblast and
promegakaryocyte counts were unchanged. The analysis of coagulation parameters
showed increased levels of fibrinogen, thrombin time, prothrombin time and
activated partial thromboplastin time in the pregnant animals. The study
suggested a hyperactivation of the coagulation system with a slight reduction in
the megakaryocyte count in bone marrow, and a reduction in platelet count in
peripheral blood at the end of pregnancy.
PMID- 27487511
TI - Serum concentrations of PIIINP aminopeptide in dogs with liver fibrosis.
AB - The aim of the study was to evaluate the serum concentration of the type III
procollagen aminopeptide in dogs, and to assess its utility in the diagnosis of
liver fibrosis. The study was carried out on 20 dogs of different breeds and of
both genders, between 7 and 15 years old. Based on the results of the
histopathological examination and the evaluation of the degree of liver fibrosis,
the dogs were divided into five groups. The mean serum PIIINP concentration in
the group of dogs with stage 1 and 2 liver fibrosis (groups 2 and 3) was five
fold higher than in healthy dogs (group 1). In turn, the mean PIIINP
concentration in the group of dogs with stage 3 (group 4) and stage 4 (group 5)
fibrosis was 10-fold higher than that of the control group (group 1). Based on
the results, we found that the serum PIIINP concentration correlated with the
degree of liver fibrosis, assessed based on a histopathological examination.
Therefore, PIIINP serum concentration tests may be a promising non-invasive
diagnostic technique that could be used in veterinary hepatology to assess the
degree of liver fibrosis.
PMID- 27487512
TI - Concentration of hepatic vitamins A and E in rats exposed to chlorpyrifos and/or
enrofloxacin.
AB - The aim of the study was to determine the level of antioxidant vitamins A and E
in the liver of rats exposed to chlorpyrifos and/or enrofloxacin. Chlorpyrifos
(Group I) was administered at a dose of 0.04 LD50 (6 mg/kg b.w.) for 28 days, and
enrofloxacin (Group II) at a dose of 5 mg/kg b.w. for 5 consecutive days. The
animals of group III were given both of the mentioned above compounds at the same
manner as groups I and II, but enrofloxacin was applied to rats for the last 5
days of chlorpyrifos exposure (i.e. on day 24, 25, 26, 27 and 28). Chlorpyrifos
and enrofloxacin were administered to rats intragastrically via a gastric tube.
The quantitative determination of vitamins was made by the HPLC method. The
results of this study indicated a reduction in the hepatic concentrations of
vitamins A and E, compared to the control, which sustained for the entire period
of the experiment. The four-week administration of chlorpyrifos to rats resulted
in a significant decrease of vitamins in the initial period of the experiment,
i.e. up to 24 hours after exposure. For vitamin A the maximum drop was observed
after 24 hours (19.24%) and for vitamin E after 6 hours (23.19%). Enrofloxacin
caused a slight (3-9%) reduction in the level of the analysed vitamins. In the
chlorpyrifos-enrofloxacin co-exposure group reduced vitamins A and E levels were
also noted, but changes in this group were less pronounced in comparison to the
animals intoxicated with chlorpyrifos only. The decrease in the antioxidant
vitamin levels, particularly noticeable in the chlorpyrifos- and the chlorpyrifos
combined with enrofloxacin-treated groups, may result not only from the increase
in the concentration of free radicals, but also from the intensification of the
secondary stages of lipid peroxidation.
PMID- 27487513
TI - Effect of neonatal or adult heat acclimation on plasma fT3 level, testicular
thyroid receptors expression in male rats and testicular steroidogenesis in vitro
in response to triiodothyronine treatment.
AB - This study aimed to evaluate the effect of heat acclimation of neonatal and adult
rats on their testes response to in vitro treatment with triiodothyronine (T3).
Four groups of rats were housed from birth as: 1) control (CR) at 20 degrees C
for 90 days, 2) neonatal heat-acclimated (NHA) at 34 degrees C for 90 days, 3)
adult heat-acclimated (AHA) at 20 degrees C for 45 days followed by 45 days at 34
degrees C and 4) de-acclimated (DA) at 34 degrees C for 45 days followed by 45
days at 20 degrees C. Blood plasma and both testes were harvested from 90-day old
rats. Testicular slices were then submitted to in vitro treatment with T3 (100
ng/ml) for 8 h. Plasma fT3 level was lower in AHA, NHA and DA groups than in CR
group. Basal thyroid hormone receptor alpha1 (Thra1) expression was higher in
testes of NHA and DA and beta1 receptor (Thrb1) in DA rats vs. other groups. In
the in vitro experiment, T3: 1) decreased Thra1 expression in all groups and
Thrb1 in DA group, 2) increased Star expression in CR, NHA and DA groups, and
Hsd17b3 expression in NHA group, 3) decreased the expression of Cyp11a1 in NHA
and DA groups, and Cyp19a1 in all the groups, 4) did not affect the activity of
steroidogenic enzymes and steroid secretion (A4, T, E2) in all the groups. These
results indicate, that heat acclimation of rats, depending on their age, mainly
affects the testicular expression of steroidogenic enzymes in response to short
lasting treatment with T3.
PMID- 27487514
TI - Influence of various carbohydrate sources on postprandial glucose, insulin and
NEFA concentrations in obese cats.
AB - Carbohydrate is an important source of energy, which can significantly affect
postprandial blood glucose and insulin levels in cats. In healthy animals, this
is not a big concern; however, in obese and diabetic animals, this is an
important detail. In the present study, the impact of four different carbohydrate
sources (glucose, maltose, corn starch, and trehalose) on short-term post
prandial serum glucose, insulin, and non-esterified fatty acid (NEFA)
concentrations was investigated with four obese cats. Each of the carbohydrate
sources was added to a commercial wet food diet for feeding the animals. A
significant difference was observed in postprandial glucose, insulin, and NEFA
area under the curve (AUC) values between each carbohydrate source in obese cats.
Furthermore, glucose and maltose induced the highest postprandial glucose and
insulin AUC values, whereas trehalose induced the lowest postprandial glucose and
insulin AUC value amongst all carbohydrate sources, respectively, in obese cats.
However, trehalose has a higher risk of inducing side effects, such as diarrhea,
as compared to other carbohydrate sources. As such, different carbohydrate
sources appear to have a very significant impact on post-prandial glycemia and
subsequent insulin requirement levels in obese cats. These results might be
useful when selecting a prescription diet for obese or diabetic cats. In
addition, maltose appears to be capable of inducing experimentally evoked
postprandial hyperglycemia in obese cats, which may serve as a good tool for use
to check the impact and effectiveness of newly developed oral hypoglycemic drugs
or supplements for cats in future experiments.
PMID- 27487515
TI - Acute phase response in the primiparous dairy cows after repeated percutaneous
liver biopsy during the transition period.
AB - The aim of this study was to evaluate the acute phase response of dairy cows to
repeated liver biopsy in order to estimate the safety of this procedure during
the transition period. Liver biopsies (up to 1000 mg of liver tissue) were
conducted twice a day, 7 days before expected parturition and 3 days after
calving. The number of needle insertions for each biopsy was recorded and was
dependent on the amount of obtained tissue. Blood samples were taken on day 7
before expected parturition, then on days 3, 4, 7 and 14 after calving. Body
temperature was measured daily in all 30 cows from day 3 until day 14 after
calving. The concentrations of haptoglobin, serum amyloid A, fibrinogen and
interleukin-6 were determined in serum and plasma. In 16.7% of cows, the rectal
body temperature rose by >= 0.5 degrees C on the day after liver biopsy. Although
the concentrations of haptoglobin, serum amyloid A and fibrinogen increased
significantly after calving (p<0.01), there was no influence of the number of
biopsies on the acute phase reaction and repeated biopsy during the transition
period had no effect on body temperature. Therefore, the procedure may be
regarded as safe for cows during the transition period.
PMID- 27487516
TI - The effects of freezing on long-term storage of canine erythrocytes.
AB - Human medicine studies have so far demonstrated that erythrocytes may be
preserved and stored at low temperatures for decades retaining their metabolic
and biochemical properties. However, detailed studies regarding this problem are
not yet available in veterinary medicine. Therefore, the objective of the current
study was to investigate time-dependent effects of long-term frozen storage of
canine red blood cells. Twelve healthy adult dogs meeting the criteria for blood
transfusion were used in the study. Whole blood samples (450 +/- 45 ml) collected
from each dog were centrifuged by a cryogenic microcentrifuge and packed RBC
suspensions were obtained. The samples were prewashed three times in 0.9% NaCl
solution and were allocated into three groups to be evaluated at three different
time points (day 0 and month 4 and 6). The samples to be frozen were subjected to
glycerolization and then stored at -80 degrees C for 4 and 6-month periods. At
the end of this period the packed RBC samples were thawed, centrifuged and then
washed in a consecutive series of dextrose solutions. 2,3-Diphosphoglycerate (2,3
DPG), Adenosin triphosphate (ATP), supernatant hemoglobin (SupHb), sodium (Na+)
and potassium (K+) levels, residual glycerol concentrations and hemograms were
evaluated and compared. Sterility tests were performed on all samples for
bacterial contamination. A statistically significant decrease was noted in
potassium levels, which was the natural outcome of deglycerolization process. No
significant change was observed in terms of other parameters due based on
different time points. In conclusion, long-term frozen storage had no negative
effect on the quality parameters of canine erythrocytes.
PMID- 27487517
TI - Flow cytometric assessment of activation of peripheral blood platelets in dogs
with normal platelet count and asymptomatic thrombocytopenia.
AB - Platelets play a crucial role in hemostasis. Their activation has not yet been
evaluated in healthy dogs with a normal and low platelet count. The aim of this
study was to determine the influence of activators on platelet activation in dogs
with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically
healthy dogs were enrolled. Patients were allocated into three groups. Group 1
consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with
a platelet count between 100 and 200*109/l and group 3 consisted of 20 dogs with
a platelet count lower than 100*109/l. Platelet rich-plasma (PRP) was obtained
from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid
(K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12
myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated.
The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61
and Annexin V served as a marker of platelet activation. The expression of
CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated
platelets had a significantly higher activity in dogs with a normal platelet
count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited
platelet activity in all groups. In conclusion, activation of platelets of
healthy dogs in vitro varied depending on the platelet count and platelet
activator.
PMID- 27487518
TI - Escherichia coli strains from ostriches and their sensitivity to antimicrobial
substances.
AB - Ostriches are bred especially for their high-quality meat. There is a lack of
knowledge concerning the ostrich's microflora. Escherichia coli is a commensal
microorganism of the poultry intestine, ostriches included. However, some strains
may become pathogenic. This study was therefore undertaken to detect coliform
bacteria in ostrich faeces and to test their antibiotic profile and sensitivity
to enterocins. Faeces (n=54, 18 mixture samples from 3 different age groups of
140 ostriches) were sampled to isolate coliform bacteria. The counts of coliform
bacteria varied from 5.69 +/- 2.4 log10 CFU/g to 5.73 +/- 2.4 CFU/g. Pure
colonies were identified using MALDI-TOF MS mass spectrometry and confirmed by
phenotypization. Seventy-one strains were allotted to the species E. coli. Sixty
four of those 71 strains caused hemolysis. They were mostly polyresistant to
antibiotics. Thirty-two poly-resistant strains of E. coli were sensitive to
enterocins. These strains were most sensitive to Ent 9296 (26 strains). Moreover,
Ent EM41 produced by E. faecium EM41 (isolated from ostrich faeces) inhibited the
growth of 20 strains, reaching activity of 100 AU/ml. Our results indicate the
possibility of enterocins being used for prevention/reduction of coliforms. Of
course, in vivo studies are also being processed.
PMID- 27487519
TI - Practical aspects of estimation of optimal time for vaccination of chicken
against IBD with use of "Deventer formula".
AB - One of the most commonly applied vaccination strategies against chicken
infectious bursal disease (IBD) is the use of live vaccines at the optimal time
estimated with the use of Deventer formula. The present study investigated the
impact of different factors on maternally derived antibodies decline and
therefore on the vaccination schedule against IBD. Our results suggest that blood
collection from birds older than 3 days is more reliable in order to estimate the
optimal date for IBD vaccination, due to disturbances in yolk sac resorption
early after hatch.
PMID- 27487520
TI - Serum malondialdehyde level and activity of total antioxidant status of dogs with
age-related cataract.
AB - STUDY OBJECTIVE: determination of malondialdehyde (MDA) level and total
antioxidant status (TAS) in the serum of dogs with age-related cataract. MATERIAL
AND METHODS: Forty dogs, 10-16 years of age, which were diagnosed with age
related cataract were examined. The control group consisted of 12 dogs, 8-13
years of age, without cataract. MDA was determined using a Perkin-Elmer LS 30
luminescence spectrometer using the method with thiobarbituric acid (TBA). TAS
was determined using the colorimetric method with a set of Randox Total
Antioxidant Status reagents. RESULTS: The results show a higher level of MDA with
statistically significant difference and lower activity of TAS in the serum of
dogs with age-related cataract. CONCLUSIONS: The results obtained indicate higher
systemic lipid peroxidation and weakening of the general defense system in dogs
with age-related cataract. These results suggest that such conditions may have an
effect on the development of age-related cataract and are consistent with the
theory of free radical age-related cataract development.
PMID- 27487521
TI - Cytodiagnostics of canine lymphomas - possibilities and limitations.
AB - Malignant lymphomas are one of the most common malignant tumours occurring in
dogs. The basic method of lymphoma diagnosis in human, as well as in canine
oncology is histopathology supported by immunohistochemistry. It was suggested
that in veterinary medicine excisional biopsy of lymph node and histopathology
should be considered only where the cytologic diagnosis is equivocal or needs to
be confirmed. There are at least three basic reasons for which cytological
examination ought to be accepted as a sufficient and reliable diagnostic method
for lymphoma in dogs. Firstly, most dog owners consider the fine-needle biopsy as
an acceptable non-harmful method of sample collection. Secondly, an increasing
number of studies recommend cytology as an accurate test for diagnosing and
subtyping canine lymphoma. Finally, the vast majority of canine lymphoma subtypes
belong to 4-5 categories characterized by a typical cytological picture.
Immunocytochemical staining of cytological smears gives new diagnostic
possibilities, such as detection of markers better characterizing given growth or
a potential goal for target therapy in individual cases (for example inhibitors
of platelet-derived growth factor).
PMID- 27487522
TI - Secretory function of adipose tissue.
AB - There are two kinds of adipose tissue in mammals: white adipose tissue - WAT and
brown adipose tissue - BAT. The main function of WAT is accumulation of
triacylglycerols whereas the function of BAT is heat generation. At present, WAT
is also considered to be an endocrine gland that produces bioactive adipokines,
which take part in glucose and lipid metabolism. Considering its endocrine
function, the adipose tissue is not a homogeneous gland but a group of a few
glands which act differently. Studies on the secretory function of WAT began in
1994 after discovery of leptin known as the satiation hormone, which regulates
body energy homeostasis and maintainence of body mass. Apart from leptin, the
following belong to adipokines: adiponectin, resistin, apelin, visfatin and
cytokines: TNF and IL 6. Adiponectin is a polypeptide hormone of antidiabetic,
anti-inflammatory and anti-atherogenic activity. It plays a key role in
carbohydrate and fat metabolism. Resistin exerts a counter effect compared to
adiponectin and its physiological role is to maintain fasting glycaemia. Visfatin
stimulates insulin secretion and increases insulin sensitivity and glucose uptake
by muscle cells and adipocytes. Apelin probably increases the insulin sensitivity
of tissues. TNF evokes insulin resistance by blocking insulin receptors and
inhibits insulin secretion. Approximately 30% of circulating IL 6 comes from
adipose tissue. It causes insulin resistance by decreasing the expression of
insulin receptors, decreases adipogenesis and adiponectin and visfatin secretion,
and stimulates hepatic gluconeogenesis. In 2004, Bays introduced the notion of
adiposopathy, defined as dysfunction of the adipose tissue, whose main feature is
insulin and leptin resistance as well as the production of inflammatory
cytokines: TNF and IL 6 and monocyte chemoattractant protein. This means that
excess of adipose tissue, especially visceral adipose tissue, leads to the
development of a chronic subclinical inflammatory condition, which favours the
development of insulin resistance and Type 2 diabetes. Obesity is a systemic
illness caused by energy transformation homeostasis disorder which results in an
increase in the amount of body fat mass. It effects approximately 40% of dogs and
20% of cats. Illnesses which accompany obesity result, to a great extent, from
the secretive role of adipose tissue, which is still little known, which should
be included when planning treatment of an obese animal.
PMID- 27487523
TI - A Unique Hybrid Quasi-Solid-State Electrolyte for Li-O2 Batteries with Improved
Cycle Life and Safety.
AB - In the context of the development of electric vehicle to solve the contemporary
energy and environmental issues, the possibility of pushing future application of
Li-O2 batteries as a power source for electric vehicles is particularly
attractive. However, safety concerns, mainly derived from the use of flammable
organic liquid electrolytes, become a major bottleneck for the strategically
crucial applications of Li-O2 batteries. To overcome this issue, rechargeable
solid-state Li-O2 batteries with enhanced safety is regarded as an appealing
candidate. In this study, a hybrid quasi-solid-state electrolyte combing a
polymer electrolyte with a ceramic electrolyte is first designed and explored for
Li-O2 batteries. The proposed rechargeable solid-state Li-O2 battery delivers
improved cycle life (>100 cycles) and safety. The feasibility study demonstrates
that the hybrid quasi-solid-state electrolytes could be employed as a promising
alternative strategy for the development of rechargeable Li-O2 batteries, hence
encouraging more efforts devoted to explore other hybrid solid-state electrolytes
for Li-O2 batteries upon future application.
PMID- 27487524
TI - A performance evaluation of a new iron oxide-based porous ceramsite (IPC) in
biological aerated filters.
AB - A novel medium containing iron oxide-based porous ceramsite (IPC) and commercial
ceramsite (CC) was used in two laboratory-scale upflow biological aerated filters
(BAFs) to treat city wastewater to compare their efficacy in wastewater
treatment. The IPC BAF and CC BAF were operated in water at 20-26 degrees C, an
air/water (A/W) ratio of: 3:1 and hydraulic retention times (HRTs) of 7, 3.5,
1.75, and 0.5 h and the removal of ammonia nitrogen (NH3-N), total nitrogen (TN),
total organic carbon (TOC), and phosphorus (P) were studied. Our results
indicated that IPC BAF was superior to CC BAF in terms of TOC, TN, NH3-N, and P
removal. IPC had higher total porosity and larger total surface area than CC. The
interconnected porous structure of IPC was suitable to microbial growth,
protozoan, and metazoan organisms were primarily found in the accumulated biofilm
layer. Biomass, in the biofilm layer, was detected at three distinct distances
(300, 900, and 1500 mm) from the bottom of the inlet filter, again indicating
that the IPC was more suitable for biomass growth. The presence of biomass
improves the simultaneous removal efficiency of nitrogen and phosphorus in the
IPC BAF. Thus, our findings support IPC as a material for use in filter media in
wastewater treatment BAFs.
PMID- 27487525
TI - Effects of intensive neuropsychological rehabilitation for acquired brain injury.
AB - The objective of the study was to examine the effects of a comprehensive
neuropsychological rehabilitation programme (Intensive NeuroRehabilitation, INR)
on the emotional and behavioural consequences of acquired brain injury (ABI). The
participants were 75 adult patients suffering from ABI (33 traumatic brain
injury, 14 stroke, 10 tumour, 6 hypoxia, 12 other), all of whom were admitted to
the INR treatment programme. The main outcome measures were: general
psychological well-being (Symptom-Checklist-90), depression and anxiety (Beck
Depression Inventory-II, Hospital Anxiety and Depression Scale, State Trait
Anxiety Inventory), and quality of life (Quality of Life in Brain Injury). The
study was a non-blinded, waiting-list controlled trial. During the waiting-list
period no or minimal care was provided. Multivariate analysis of the main outcome
measures showed large effect sizes for psychological well-being (partial eta2 =
.191, p < .001), depression (partial eta2 = .168, p < .001), and anxiety (partial
eta2 = .182, p < .001), and a moderate effect size for quality of life (partial
eta2 = .130, p = .001). Changes on neuropsychological tests did not differ
between the groups. It was concluded that the INR programme improved general
psychological well-being, depressive symptoms, anxiety, and quality of life. The
programme does not affect cognitive functioning.
PMID- 27487526
TI - Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the
Spine and Hip in Postmenopausal Women With Low Bone Mass.
AB - Romosozumab, a monoclonal antibody that binds sclerostin, has a dual effect on
bone by increasing bone formation and reducing bone resorption, and thus has
favorable effects in both aspects of bone volume regulation. In a phase 2 study,
romosozumab increased areal BMD at the lumbar spine and total hip as measured by
DXA compared with placebo, alendronate, and teriparatide in postmenopausal women
with low bone mass. In additional analyses from this international, randomized
study, we now describe the effect of romosozumab on lumbar spine and hip
volumetric BMD (vBMD) and BMC at month 12 as assessed by QCT in the subset of
participants receiving placebo, s.c. teriparatide (20 ug once daily), and s.c.
romosozumab (210 mg once monthly). QCT measurements were performed at the lumbar
spine (mean of L1 and L2 entire vertebral bodies, excluding posterior processes)
and hip. One year of treatment with romosozumab significantly increased integral
vBMD and BMC at the lumbar spine and total hip from baseline, and compared with
placebo and teriparatide (all p < 0.05). Trabecular vertebral vBMD improved
significantly and similarly from baseline (p < 0.05) with both romosozumab
(18.3%) and teriparatide (20.1%), whereas cortical vertebral vBMD gains were
larger with romosozumab compared with teriparatide (13.7% versus 5.7%, p <
0.0001). Trabecular hip vBMD gains were significantly larger with romosozumab
than with teriparatide (10.8% versus 4.2%, p = 0.01), but were similar for
cortical vBMD (1.1% versus -0.9%, p = 0.12). Cortical BMC gains were larger with
romosozumab compared with teriparatide at both the spine (23.3% versus 10.9%, p <
0.0001) and hip (3.4% versus 0.0%, p = 0.03). These improvements are expected to
result in strength gains and support the continued clinical investigation of
romosozumab as a potential therapy to rapidly reduce fracture risk in ongoing
phase 3 studies. (c) 2016 American Society for Bone and Mineral Research.
PMID- 27487527
TI - Evaluation of the Biotoxicity of Tree Wood Ashes in Zebrafish Embryos.
AB - Ashes derived from biomass combustion and used as soil fertilizers can generate
negative environmental and human health risks, related to leaching of heavy
metals and other putative toxic elements. Tree wood ash composition may vary
depending on geographical location and surrounding industrial processes. In this
study, we evaluated the biotoxicity of lixiviated tree wood ash samples from
trees of the Ash (Fraxinus), Cherry (Pronus), Hazel (Corylus), and Black locust
(Robinia) genus collected in an industrialized region in Northern Italy.
Elemental chemical analysis of the samples was performed by total reflection X
ray fluorescence technique and their biotoxicity was assessed in zebrafish (Danio
rerio) embryos. Ashes from Ash, Cherry, and Hazel trees, but not Black locust
trees, had a high concentration of heavy metals and other putative toxic
elements. Accordingly, a dose-dependent increase in mortality rate and
morphological and teratogenic defects was observed in zebrafish embryos treated
with lixiviated Ash, Cherry, and Hazel tree wood samples, whereas the toxicity of
Black locust tree wood ashes was negligible. In conclusion, lixiviated wood ashes
from different plants show a different content of toxic elements that correlate
with their biotoxic effects on zebrafish embryos. Tree wood ashes derived from
biomass combustion may represent a potential risk for the environment and human
health.
PMID- 27487528
TI - [Two compartment model of body composition and abdominal fat area in
postmenopausal women - pilot study].
AB - INTRODUCTION: Both menopausal period and aging have influence on body
composition, increase of total body fat and visceral fat in particular. We should
be aware that changes in body composition, mainly fat translocation to abdominal
region, can occur without significant changes in body weight. Therefore
quantitative abdominal fat assessment should be our aim. THE AIM: Body
composition analysis based on two compartment model and abdominal fat area
assessment in cross section. MATERIAL AND METHODS: Subjects in postmenopausal
period (41 women) were recruited for this study and divided into 2 groups: group
1 - women aged 45-56 years and group 2 - women aged 57-79 years. Body composition
analysis and abdominal fat area assessment were conducted by using bioelectrical
impedance method with BioScan 920 (Maltron int.) accordingly with standardized
procedure. RESULTS: Women in early postmenopausal stage (Group 1) had
statistically significant lower total body fat percentage in comparison with
women in late postmenopausal period (Group 2) (41.09 +/- 7.72% vs. 50.7 +/-
9.88%, p=0.0021). Also women in group 1 were characterized by significant lower
visceral fat area (VAT) as well as subcutaneous fat area (SAT) in comparison with
group 2 (respectively VAT 119.25 +/- 30.09 cm2 vs. 199.36 +/- 87.38 cm2,
p=0.0011; SAT 175.19 +/-57.67 cm2 vs. 223.4+/-74.29 cm2, p=0.0336). According to
VAT criteria (>120 cm2), 44% of women in group 1 and 80% in group 2 had excess of
visceral fat. CONCLUSIONS: Both total body fat and intra-abdominal fat increased
with age, independently of weight changes.
PMID- 27487529
TI - [Life satisfaction and self-esteem among women in the menopausal time].
AB - INTRODUCTION: The period of menopause is usually a long-lasting, running process,
with strong hormone changes which are manifested with somatic disorders and the
lability of the emotional state. The degree of severity of the occurence of these
symptoms can be variously bolstered. These changes can affect the quality of life
and ones self-esteem. THE AIM: To assess the level of self-esteem of
biopsychosocial functioning women in the menopausal time and the impact of
menopause on women's quality of life. MATERIAL AND METHODS: A group of 90 women
in perimenopausal aged 49-61 were enrolled in the study. Standardized
psychological questionnaires (Kupperman Index, SES Rosenberg and WHOQoL-BREF)
were used. Additional data was collected by using a questionnaire developed by
the authors. In statistical analysis chi2, analysis of variance and Spearman's
rank correlation models were used. RESULTS: A significant correlation
relationship between level of education and the sphere of psychological
evaluation (p <0.05); and between the place of residence, and the assessment of
the quality of life in the social (p <0.1) and environmental (p <0.1) sphere.
Among the respondents, 95.45% of women received the result of the scale SES > 25
indicating the correct (in the normal or higher range) self-esteem. CONCLUSIONS:
In the studied group, women believe that they have the correct (in the normal or
higher range) self-esteem. The surveyed women found as good their quality of
life, the highest rated was social and psychological sphere, the lowest score
received sphere of physical functioning (somatic). A statistically significant
correlations were achieved between home and professional activity, and the
assessment of the quality of life in the social and environmental sphere. The
analysis showed a significant association correlation between level of education
of women and the sphere of psychological evaluation.
PMID- 27487530
TI - [Modern look at pharmacotherapy of osteoarthritis accomplished with
cardiovascular disease].
AB - ABSTR ACTCT Introduction: At present, the main pathogenetic link in the
development of OA as atherosclerosis is chronic inflammation, which is based on
the activation of pro-inflammatory mediators and disorders of cholesterol
metabolism. The aim of the research was to study the efficiency of the use of
rosuvastatin in the treatment of patients with osteoarthritis in the combined
arterial disease. MATERIAL AND METHODS: The study was conducted on the basis of
the Poltava Regional Clinical Hospital. N.V. Sklifosovsky and Research Institute
of Genetic and immunological bases of pathology and pharmacogenetics higher state
educational institution of Ukraine "Ukrainian Medical Dental Academy" (HSEEU
"UMUMCA"). Results of treatment of 30 patients with osteoarthritis and
hypertension who received treatment with rosuvastatin. CONCLUSIONS: It was
concluded that the use of rosuvastatin in these patients can reduce pain, improve
joint function, reduce disease activity and improve quality of life for patients.
Besides rosuvastatin does not affect the level of systolic and diastolic blood
pressure and can be used with concomitant hypertension.
PMID- 27487531
TI - [Harmful alcohol consumption: prevalence, trends, health burden, reduction
strategy].
AB - INTRODUCTION: Harmful alcohol consumption constitutes a significant cause of the
global burden of disease, causing more than 200 different diseases, 5.9% of all
deaths worldwide, causing substantial medical and social costs, major economic
loss, slowing progress towards the strategic goals of human development. THE AIM:
to substantiate approaches to the formation of a national strategy to combat the
harmful use of alcohol in Ukraine based on the analysis of the prevalence of
alcohol consumption and related health and social problems and international
experience and recommendations of WHO. MATERIAL AND METHODS: The study was based
on analysis of the extent and patterns of alcohol consumption in Ukraine, levels,
structure and dynamics of morbidity and mortality from diseases associated with
alcohol abuse; investigation of preventive activities in primary healthcare, the
existing problems and doctors' needs for prevention alcohol abuse, national and
international experience on this problem.This work usesbibliosemantic, medical,
statistical, sociological, epidemiological methods. The information base are:
European Health for All Database (HFA-DB)for 2000-2012,Center of Medical
Statistics, Ministry of Health of Ukraine for 2000-2015, questionnaire survey of
physicians in primary care, strategic and policy documents of WHO, WHO Regional
Office for Europe. RESULTS: In Ukraine, as in most countries in the WHO European
Region prevalence of alcohol is high. In the ranking of the WHO European Region
Ukraine ranks fifth in alcohol consumption per capita. The structure of
consumption of alcoholic drinks is dominated by strong spirits (48%). There has
been a negative trend for this indicator from 5.4 liters in 2002 to 15.6 liters
in 2012.The dominant pattern of alcohol consumption is characterized by early
onset of alcohol consumption, significant frequency, large doses, mostly strong
alcohol beverages, with significant share of low-quality alcohol. This factor
contributes to high levels of morbidity. A total of546.3 thousandpeople with
mental and behavioral disorders due to use of psychoactive substances
wereregistered in health care facilities in 2014. Standardized mortality rate
from causes related to alcohol in Ukraine (185.4 per 100 thousand.) is one of the
largest in Europe, with only Kazakhstan (308.4) and Belarus (187.9) being behind.
Regular work aiming at prevention of alcohol abuse is carried out by 49.4% of
primary care professionals; 21.3% of physiciansinsist on reducing alcohol use on
occasion. CONCLUSION: Alcohol abuse is a major factor of morbidity, epidemic of
noncommunicable diseases in Ukraine, causing significant medical and social costs
and economic losts.Ukraine ranks fifth in alcohol consumption per capita among
WHO European Region countries. High level and unhealthy patterns of alcohol
consumption in the population causes high morbidity and mortality from
noncommunicable diseases, accidents, exceeding pan-European indices and
indicators in the European Union. Primary health care facility staff has
insufficient knowledge, skills and gaps in professional training regarding the
prevention of harmful use of alcohol.There is a high need for effective
strategies to reduce the prevalence of this risk factor in Ukraine. In developing
the National Action Plan to reduce the harmful use of alcohol, a national context
and WHO recommendationsshould be considered, including improving the efficiency
of health services, high-quality prevention and effective treatment of disorders
caused by alcohol, countermeasures on driving drunk, limiting the sale and
availability of alcohol, prevention the spread of manufacturing and marketing of
alcoholbeverages produced illegally, including falsification, the revitalization
of local communities, weakening the impact of marketing of alcohol beverages.
PMID- 27487532
TI - Risk factors for development of hypertension in poltava region.
AB - INTRODUCTION: Given the very dangerous situation in relation to cardiovascular
morbidity, purpose of the study was to identify the main risk factors of
hypertension among the population of Poltava region, to determine their role in
the formation of this pathology. AIM: study the factors for development of
hypertension in Poltava region Material and methods: The study was conducted by
anonymous questionnaires of adults of Poltava region (1285 individuals in 2
groups: 563 individuals with hypertension, 722 people - healthy). The data,
obtained in the study, were processed using special software - IBM SPSS Statistic
Version 22.0. By logistic regression were identified risk factors that
significantly affect the development of hypertension. RESULTS: According to the
study identified major, statistically significant risk factors of hypertension
among the population of Poltava region. Proved reliable impact these risk
factors: age (over 40 years) - OR - 7.9, CI - 6,132-10,176, (p<0,001), gender
(male) - OR - 1.899, CI - 1,512-2,386, (p<0,001), BMI (obesity) - OR - 3.9632, CI
- 2,881-4,580, (p<0,001), smoking - OR - 1.918, CI - 1,263-2,913, (p=0,002),
consumption of dairy products (occasionally) - OR - 1,553, CI - 1,215-1,985,
(p<0,001), consumption of pork (often) - OR - 1,805, CI - 1,422-2,290, (p<0,001),
consumption of beef (occasionally) - OR - 1,547, CI - 1,229-1,949, (p=0,006),
consumption of smoked meat (often) - OR - 1,341, CI - 1,070-1,678, (p=0,006),
consumption of sweets (often) - OR - 1,510, CI - 1,210-1,884, (p<0,001), night
sleep (restless) - OR - 1,762, CI - 1,279-2,426, (p<0,001), duration of sleep
(less than 6 hours) OR - 1,648, CI - 1,126-2,411, (p=0,01), physical activity
(low) - OR - 2,734, CI - 2,102-3,555, (p<0,001), nature of the rest (passive) -
OR - 2,476, CI - 1,970-3,112, (p<0,001), feeling stress (always) - OR - 1,537, CI
- 1,227-1,926, (p<0,001), relations at home (tense) - OR - 3,072, CI - 1,517
6,221, (p=0,001), CVD in the family - OR - 1,397, CI - 1,110-1,758, (p=0,004),
discomfort in the heart aria - OR - 3,090, CI - 2,453-3,893, (p<0,001), self
treatment - OR - 1.942, CI - 1,553-2,428, (p<0,001). CONCLUSIONS: The study found
regional differences in risk factors of hypertension among the population of
Poltava region, emphasized the need to increase attention of health professionals
of primary care for problems of cardiovascular disease, make a point of the need
to intensify primary prevention, modernization of behavior on health among
population, promotion of the principles of a healthy lifestyle.
PMID- 27487533
TI - [Upgrading of complete removable prosthetic appliance of stomatological patients
by the use of new base materials].
AB - INTRODUCTION: The effectiveness of orthopedic treatment of edentulous patients
depends on the properties of the basic materials. The main group of materials for
manufacturing of such structures are acrylic plastics of thermal polymerization.
However, many years of experience in the use of plastics has revealed a number of
shortcomings. One of the main is insufficient functional durability of
prostheses, and as a consequence - the fragility of acrylic constructions. At
present, more and more dentists use nonacrylic thermoplastics, which can improve
the functional quality of full removable dentures, as well as, avoid the above
disadvantages of acrylic basic plastic. AIM: The work is devoted to the study of
comparative clinical effectiveness of dental prosthetic in edentulous patients
using a variety of basic materials for the production of removable dentures.
MATERIAL AND METHODS: In this work we used the following materials - "Ftorax" -
acrylic plastic of hot polymerization and "Vertex Thermosense" - nonacrylic
thermoplastic plastic. RESULTS: As a result of the performed work it can be
concluded that the use of the basic thermoplastic materials, namely "Vertex
Thermosense", allows to get more rapid adaptation of the patient to full
removable dentures due to better fixation and stabilization. CONCLUSION: Based on
the results of our comparative clinical study it can be recommended using of base
material "Vertex Thermosense" in the clinic of prosthetic dentistry in treatment
of edentulous patients.
PMID- 27487534
TI - Quality of life in patients with nonalcoholic fatty liver disease in combination
with essential hypertension considering taste sensitivity to sodium chloride.
AB - INTRODUCTION: Nonalcoholic fatty liver disease and hypertensive disease - is the
most common combination of abnormalities that occur in people suffering from
metabolic syndrome. Their combination not only causes concurrent damage of the
liver and the heart, caused by common pathogenic beginning, and also mutually
complicate the disease course of each other. The leading role in the development
of nonalcoholic fatty liver disease belongs to abdominal obesity and insulin
resistance, and is seen as a manifestation of liver disease in metabolic
syndrome. Genetic predisposition, lifestyle, improper nutrition, including
excessive use of sodium chloride, lead to excessive formation of visceral adipose
tissue with development of abdominal obesity, which is a likely criterion of
insulin resistance. The long course of nonalcoholic fatty liver disease in
combination with essential hypertension in excessive consumption of sodium
chloride may negatively affect their quality of life. The aim of the study is to
find out the features of quality of life in patients with nonalcoholic fatty
liver disease in combination with hypertensive disease with different taste
sensitivity to sodium chloride. MATERIAL AND METHODS: We have investigated the
quality of life of 65 patients with nonalcoholic fatty liver disease in
combination with hypertensive disease II stage with different taste sensitivity
to sodium chloride. Salt taste sensitivity threshold to sodium chloride is
determined by the method of R. Henkin. Assessment of quality of life was
performed using the Ukrainian version of the questionnaire Medical Outcomes Study
Short Form 36 (MO S SF-36). RESULTS: Was revealed that in patients with
nonalcoholic fatty liver disease in combination with hypertensive disease II
stage with high salt taste sensitivity threshold observed the decline in the
quality of life that manifests as a decline in physical condition (especially of
the physical functioning, physical role functioning and general health
perceptions) and mental health (especially social functioning). Also the
increased salt intake and salt appetite in patients with high salt taste
sensitivity threshold were noted (p <0,05). CONCLUSIONS: Reducing the use of
sodium chloride can be a preventive measure easier than a decrease in body
weight, and one that will reduce the body weight, especially in people with
nonalcoholic fatty liver disease in combination with hypertensive disease, can
reduce the risk of complications and improve quality of life in patients.
PMID- 27487535
TI - [Cytokine profile in young children with acute stenotic laryngotracheitis].
AB - INTRODUCTION: One of the most severe complications of acute respiratory
infections in young children is acute stenotic laryngotracheitis (croup). The
relationship between cytokine blood levels and symptoms of croup, croup severity,
disease sequel, despite numerous studies is still unclear. AIM: Cytokine profile
in young children with acute stenotic laryngotracheitis investigation. MATERIAL
AND METHODS: 112 children aged 12 min. - 36 mon. with acute stenotic
laryngotracheitis which were treated at the Lviv Regional Infectious Diseases
Hospital were kept under observation. Croup symptoms, levels of interleukins
(IL1, IL4, IL6, IL10, IL17) in serum, DNA and RNA viruses in respiratory nasal
mucus were studied; Chan croup severity was used. RESULTS: In the pathogenesis of
croup has an important role the imbalance between inflammatory (IL1, IL6) and
anti-inflammatory (IL4, IL10, IL17) cytokines, which does not reduce the
intensity of inflammatory reactions and its lead to local swelling, muscle spasm,
excessive production of mucus in the place of viral replication. The levels of
inflammatory and anti-inflammatory cytokines in the blood serum of children with
croup were significantly higher than in patients with acute laryngitis. In
patients with recurrent croup, unlike patients with the first case of croup does
we don't see a significant correlation between the concentrations of inflammatory
and anti-inflammatory cytokine levels Conclusions: The significantly higher
levels of cytokines in children with croup compared with the group of patients
with acute laryngitis were found, imbalance between anti-inflammatory (IL1, IL6)
cytokine levels and inflammatory (IL4, IL10, IL17) cytokine levels in children
who developed recurrent croup.
PMID- 27487536
TI - [Evaluation of therapy efficiency in patients with combined course of copd and
osteoarthritis].
AB - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a disease that is
characterized by chronic airflow limitation, a variety of pathological changes in
the lungs, significant extrapulmonary manifestations, and severe comorbidities
which may further aggravate the course of COPD [GOLD, 2013]. Intensity of
systemic manifestations increases with the progression of obstruction, therefore
the abovementioned symptoms are often overlooked and become apparent in the later
stages of the disease. Systemic manifestations impair the quality of life, lead
to early disability and significantly contribute to mortality in patients with
COPD. Diseases of cardiovascular and musculoskeletal systems are the most serious
and socially significant systemic manifestations of chronic obstructive pulmonary
disease. Currently, there is no doubt that the activation of non-specific and
specific immune responses in patients with COPD is associated with the influence
of a number of universal mediators, among which a special place belongs to the
cytokine network that controls implementation processes of the immune and
inflammatory reactivity. The aim of our work was to increase the effectiveness of
treatment in patients with chronic obstructive pulmonary disease in combination
with osteoarthritis based on the study of clinical course, assessment of
patient's life quality and substantiation of pharmacological correction. MATERIAL
AND METHODS: The work was conducted on the basis of Poltava Regional Clinical
Hospital named after N.V. Sklifosovskiy. The study was carried out at Research
Institute for Genetics and Immunological Grounds of Pathology and
Pharmacogenetics of Higher State Educational Establishment of Ukraine "Ukrainian
Medical Stomatological Academy" (HSEEU "UMUMCA"). The study involved 40 patients
with an average age of 54.4 +/- 3.1 years with acute exacerbation of COPD
(clinical group B-C - GOLD II-III), in combination with OA. The duration of COPD
was 16.2 +/- 2.1 years. Among patients there were 28 (70%) men and 12 (30%)
women. All patients were smokers; the smoking period was 32.4 +/- 2.9 pack-years.
OA in the phase of unstable remission was verified in all patients, large joints
were involved - knee, shoulder, and ankle. Depending on the chosen option of
treatment, patients were divided into two representative groups - I and II.
Patients of group I received only standard treatment for COPD in accordance with
existing protocols, and in group II fenspiride hydrochloride 80 mg 2 times a day
was added to the basic therapy for 12 days. Full examination of patients was
carried out at admission and after 3 months from the date of admission. RESULTS:
According to the study, on addition of fenspiride to basic therapy in patients
with constellation of COPD and OA, the regression of disease (reduction in cough)
was observed by 2.9 +/- 0.4 days earlier, dyspnea by 2.3 +/- 0.33 than in the
comparison group (p < 0.05), quality of life improved, and exercise tolerance
increased. FEV1 in patients of group I after 3 months amounted to 62.6 +/- 4.2%,
in group II - 68.1 +/- 4.9%, recurrence of airflow obstruction in both groups
increased: in group I - by 4.2 +/- 1.1%, in group II - by 5.6 +/- 1.5%. Adding
fenspiride hydrochloride to the treatment significantly improved the life quality
of patients with COPD combined with OA at all scales of SF-36 questionnaire,
reflecting the patient's physical condition, namely, physical activity, the role
of physical problems in vital functions, the intensity of pain, overall health
status, vitality. After 3 months of follow-up, in patients with comorbidity
influenced by fenspiride hydrochloride against the background of traditional
pathogenic therapy, the indicators of VAS significantly decreased by 1.9 times
(3.18 +/- 0.24 cm versus 6.01 +/- 0.59 cm, p <0, 05), Lequesne index - by 2.0
times (9.42 +/- 1.81 points against 19.17 +/- 4.15 points, p <0.05) and WOM AC by
1.6 times (38.7 +/- 3.7 points against 63.8 +/- 8.3 points, p <0.05),
respectively. In patients of group II, a more pronounced positive dynamics of
reducing inflammatory activity, confirmed by the decrease in TNF-alpha content by
1.9 times (61.8 +/- 5.9 pg / ml versus 131.5 +/- 6.9 pg / ml, p <0.001) was
observed. The hospitalization period of patients in group I was 14.3 +/- 0.4
days, in group II it was less and amounted to 12.9 +/- 0.5 days. CONCLUSIONS:
Supplementary application of fenspiride hydrochloride in the treatment of COPD
patients in combination with OA improves the outcomes of patients' treatment,
quality of life and prolongation of remission, indicating a decrease in the
severity of systemic inflammation.
PMID- 27487537
TI - Specific features of cytological and colposcopical pattern in pregnant women with
benign cervix uteri pathology in anamnesis.
AB - INTRODUCTION: a tendency of increasing incidence of the cervix uteri precancer
and cancer in women of reproductive age is noticed recently being related to the
growth of number of the sexually-transmitted infections. The cervix uteri
pathology incidence in women of fertile age is 20-25%. AIM: to study the specific
features of the cytological and colposcopical pattern in pregnant patients with
benign cervix uteri pathology in the anamnesis and the character of its change
post partum. MATERIAL AND METHODS: we have examined 195 women during their
pregnancy and 3-5 months post partum. All pregnant women, alongside with
generally accepted clinical and laboratory examinations, were subjected to the
simple and extended colposcopy, cytology of the targeted smears and, according to
indications, the histological studies of bioptate. RESULTS: according to the
results of the colcoscopical studies and the signs of the cervix uteri pathology
found, the patients were divided into several groups. A control group included 49
pregnant women. The clinical and instrumental examination of 146 women with
cervix uteri pathology has been carried out both during pregnancy and post
partum. CONCLUSIONS: the structure of the clinical forms of benign and
premalignant changes in the cervix uteri epithelium in pregnant patients has been
found. Specific features of the cytological and colposcopical pattern in pregnant
patients with benign cervix uteri pathology in anamnesis have been studied. The
relationship between the parity of pregnancy, delivery, route of delivery and
regress of both benign and premalignant changes in the cervix uteri epithelium 3
5 months post partum has been determined.
PMID- 27487538
TI - Advanced endodontic developments in pulpectomy of primary teeth.
AB - INTRODUCTION: To appraise studies about pulpectomy in primary teeth with nickel
titanium rotary files and smear layer removal and to find out may these
developments enhance pulpectomy outcomes in primary teeth. MATERIAL AND METHODS:
A systematic search was implemented for PubMed, Google and Google Scholar between
the years 1995-January 2016 to identify eligible studies. Studies design was
established according to the CEBM recommendations. Evidence quality of studies
was appraised by risk of bias. RESULTS: Six studies about pulpectomy met the
inclusion criteria, of which five were randomized controlled trials. Only one
research demonstrates the enhanced outcome of pulpectomy in primary teeth with
smear layer removal. Chosen studies have low overall evidence quality.
CONCLUSIONS: Given the paucity, high heterogeneity of high-quality articles and
their level of bias, recommendation for the use of nickel-titanium rotary files
and smear layer removal in pulpectomy in primary teeth can yet not be formulated.
PMID- 27487539
TI - [Skin cancer of the nose - methods and results of surgical treatment].
AB - BACKGROUND: Non-melanoma skin cancer particularly basal cell carcinoma is the
most common human malignancy in Caucasians. The majority of these tumours (80
90%) arise on the sun exposed parts of face. Lesions of the nose are the most
challenging for the surgeon, because of the aesthetic feature. THE AIM: The aim
of the study is to evaluate results of surgical treatment of nose skin cancer.
MATERIALS AND METHOD: Authors analysed retrospectively 23 cases of skin cancer of
the nose. Demographic data, aesthetic units, surgical methods and complications
as well as aesthetic and functional results of treatment were noted. RESULTS: 23
people (9 male and 14 female) with 23 skin lesions were included to the study.
The mean age was 72 +/- 13 years. Majority of tumours infiltrated more then 1
nose aesthetic subunit. The most common surgical method of reconstruction was
bilobed flap. Most of patients presented good aesthetic and functional outcome.
CONCLUSIONS: The most important stage of treatment is proper qualification to
surgical treatment - selection of reconstruction method, what establish
radicalness of resection and good aesthetic and functional results.
PMID- 27487540
TI - [Reliability and validity of assessment of educational outcomes obtained by
students of Medical Rescue at Medical University of Warsaw].
AB - INTRODUCTION: In the interest of preservation of high degree of objectivity of
information about students' educational outcomes, a system of assessment needs to
meet criteria of appropriate reliability and validity. THE AIM: Analysis of
reliability and validity of the system of assessment of students' educational
outcomes for courses followed by an examination and covered by a curriculum in
Medical Rescue at Medical University of Warsaw (MU W). MATERIALS AND METHODS: A
retrospective study enrolling a group of 421 students of eight subsequent full
education cycles. Detailed data concerning grades for fourteen courses followed
by an examination in the entire course of studies were collected. Reliability
(Cronbach's alpha coefficient) and criteria validity (Spearman's rank
correlation) were assessed. Internal consistency was estimated using a multiple
regression model. RESULTS: The levels of assessment reliability for the general
university, pre-clinical, and clinical scopes amounted to alpha: 0.42, 0.53, and
0.70, respectively. The strongest positive correlations between the results of
pre-clinical and clinical trainings were found for the Anatomy course (r ~ 0.30).
Only in the case of the Pharmacology course it was found that students'
achievements in this field were significantly correlated with all other courses
of clinical training. The influence of educational outcomes in particular areas
of clinical training on the final grade for the entire course of studies was
diverse (beta regression between 0.04 and 0.11). While the Pharmacology course
had the strongest impact on final results, the Surgery course had the least
influence on students' final grades (beta = 0.04). CONCLUSIONS: 1. Sufficient
reliability of the system of assessment of educational outcomes in Medical Rescue
showed good precision and repeatability of assessment. 2. A low level of validity
was caused by a failure to keep the appropriateness of the assessment of
educational outcomes in several clinical courses. 3. Prognostic and diagnostic
validity of methods used for evaluation of competencies of Medical Rescue
students at WMU needs to be assessed in the future.
PMID- 27487541
TI - [Pathological changes in the microstructure of the sensomotor cortex of white
rats with experimental subarachnoid hemorrhage and after experimental
influences].
AB - INTRODUCTION: Many works are dedicated to research in the experiment of the
cerebrovascular diseases and correction of pathological changes. Among these
studies we have not found devoted czuciowo-ruchowej changes cortex of rats
subarachnoid hemorrhage. MATERIAL AND METHODS: The study was conducted on 18
white rats weighing 220-310 g. The model of subarachnoid hemorrhage (SAH) was
created on the base of methodology described by Dudhani RV et al. (2013). SAH
develops immediately after injection of autologous arterial blood into the
subarachnoid space. Five animals underwent everyday intraperitoneal injection of
NO Donator (L-arginine aspartate) for 8 days from the beginning of the
experiment. Sampling of the biological material carried on the ninth day after
euthanasia of the test animals under anesthesia with diethyl ether. RESULTS:
Swollen, rounded shape neurons were observed while watching the microscope slides
of rat brain samples after autologous blood injection. Otherwise, others cells in
the same sample looked atrophous, of reduced size, shrunken. There was observed
increase in surface area to 623.1 +/- 36.0 MUm2 and volume of neurons to 949.8+/
78.0 mkm3, significant compared to healthy animals. The severity of pathologic
changes was lower in group of therapy by NO donator, namely, the bodies of
neurons of the similar size, their shape is almost triangular, most neurons also
as macroglial cells have close to normal structure and pericellular zone.
CONCLUSIONS: SAH evokes a number of pathological changes in the rats' brain
sensomotor cerebral cortex. Modeling of the SAH leads to significant (p<0,01)
morphometric changes in the pyramidal neurons, namely, to increase of the surface
of nerve cells in an average up 1.33 times and 1.5 times - of the volume. Therapy
by NO donator of animals with model of SAH reduces the severity of cells' lesion,
the majority of neurons and macroglial cells have the shape and pericellular
spaces close to the normal.
PMID- 27487542
TI - [The questions of improving the information-analytical component in the reform of
the health care system in Ukraine].
AB - INTRODUCTION: A priority task of the development strategy of the Ukrainian health
care system is the saving and improving of public health. With the development of
new economic relations, health care restructuring, the introduction of new
financing mechanisms to policy-makers have an important task of the organization
of operational management on the basis of timely quality information. According
to many authors, the ability to improve the quality of the received information
is possible due to the intercalation of information technologies. The main aim of
our study is to determine the main directions of modernization of information
analytical component during the health care reform. MATERIAL AND METHODS: The
medical institutions reporting forms (f.20, f.12, f.17, f.47) were analyzed to
achieve the goal, were conducted a survey of primary care physicians. The survey
was attended by 265 family doctors, 80 of whom are family doctors of family
medicine clinic of the regional center, 185 - medical centers of primary health
care district centers. RESULTS: The analysis of the sociological research
indicates that the work of the family doctor is accompanied by filling a large
number of records, so according to the survey, an average of doctors per day
filled about 15.74 +2.2 registration forms, on average per month 333,7+ 30 a
month. The necessity of reform of the information-analytical component of the
health care system have noted by 94% 1.4. Do not have a automated workstation
34.5% + 5.3 physicians of the regional center and 68% + 3.4 countryside.
Possession of the computer at user level observed by 92% + 1.6, which is a good
basis for the introduction of information in healthcare system. CONCLUSIONS: The
data of the sociological survey confirm the necession of structural-functional
procuring of the system of information-analytical supporting of the healthcare
system of Ukraine. Annual health statistics reports are still relevant, but they
need to improve and adapt to the new conditions of functioning of healthcare
system and should be subject to automated processing of data at all levels.
PMID- 27487543
TI - [Analysis of orthodontic treatment efficiency in children with dental crowding].
AB - INTRODUCTION: Efficiency of dental treatment is necessary to provide optimal
results with less outlay of clinical time and shorter duration of treatment and
for stable and balanced occlusion. AIM: To compare duration of orthodontic
treatment in children with dental crowding by authoring and traditional methods.
MATERIAL AND METHODS: Orthodontic treatment of 37 patients with dental crowding
of severe degree in period of mixed dentition was carried out. The first (1)
(basic) group consisted of 27 patients (mean age 11,93+/-0,73 years) who were
treated with removable orthodontic appliances of our own design and additional
application of own theoretical and practical developments. Control group (2)
consisted of 10 patients (mean age 12,6+/-1,28 years). They were treated by
traditional removable appliances with screws. Student's t-test was applied to
reveal significanse deference of the obtained results for different groups.
Before treatment comparative analysis has not showed significant difference
between groups depending on age, gender, sagittal, vertical and lateral
malocclusion as well as localization and severity degree of dental crowding (P
>0,05). RESULTS: It was found that treatment duration of malocclusion with dental
crowding of the maxillary teeth for groups 1 and 2 was 11,95+/-0,85 and 18,75+/
2,61 months respectively (P >0,05) . Duration of treatment for groups 1 and 2 of
mandibular teeth crowding was 12,47+/-1,09 and 17,86+/-1,81 months respectively
(P >0,05). CONCLUSIONS: It was proved that the application of own theoretical and
practical developments which were introduced in orthodontic treatment of
malocclusion complicated by dental crowding, makes it possible to reduce period
of treatment on the average in 1,45 times in comparison with conventional.
PMID- 27487544
TI - [Planning of volume and terms of orthodontic treatment of patients with
transversal maloclusion].
AB - INTRODUCTION: In planning of orthodontic treatment, as well as the alleged end of
the treatment of orthodontic patients with transversal malocclusion should first
pay attention to the treatment of opportunistic diseases that can affect the
outcome of treatment of orthodontic patients (for example, rehabilitation of the
nasopharynx, the treatment of rickets, the treatment of scoliosis posture,
scoliosis ). THE AIM: definition of related factors affecting the volume and
timing of the treatment of patients with transversal malocclusion. MATERIAL AND
METHODS: There were examined 32 patients with transversal malocclusion, and
studied their medical history (Form 043). Patients were examined by standard
algorithm survey. Two groups of patients by sex: Group 1: girls - 16 people and 2
th group: boys- 16 people. The material collected from 2010 to 2015. Patient age
12-17 years. RESULTS: Subjective attitude to the disease formed on the basis of
a number of factors that can be grouped into the following categories: social and
constitutional and individual psychological. Since incorrect posture and
malocclusion are the cause and effect of each other, in such cases should be
treated at the same time and bite and pathology of the musculoskeletal system
(10, 11). It is clear that in the planning of orthodontic treatment should be
part and treatment of posture and a close and fruitful collaboration with the
doctor traumatologist orthopaedist. CONCLUSIONS: The sex of the patient,
especially temperament, the doctor-patient relationship, as well as the presence
of somatic diseases have a significant impact on the length and complexity of the
orthodontic treatment.
PMID- 27487545
TI - [The use of methotrexate in an inflammatory bowel diseases based on the review of
the current literature].
AB - M ethotrexate (MTX) as an immunomodulatory drug has numerous applications in
autoimmune diseases. Autoimmune patomechanism is one of the factors responsible
for development of inflammatory bowel diseases (IBD). MTX is an alternative
therapy in the treatment of IBD. Over the past several years clinical trials has
confirmed the efficacy of MTX in the treatment of Crohn's disease (CD). Data
concerning use of MTX in ulcerative colitis (UC) are not as numerous as in the
CD. Currently, MTX is recommended for the induction treatment and maintenance
therapy in CD patients, especially in steroid-dependent patients, disease
refractory to corticosteroids, no improvement after treatment with azathioprine
and 6-mercaptopurine, or in case of intolerance to these drugs. Preferred route
of administration in the treatment of CD is parenteral supply. Contraception is
indicated during MTX treatment since it's teratogenic.
PMID- 27487546
TI - [Immobilize the person after injury - problems in the practice of the rescuer].
AB - The rescuer often has to deal with patients who have suffered trauma to the bone
, including heads, spine, lower and upper limbs. Serious injuries or multiorgan
grudges are a frequent result of communicative cases, and a fast but accurate
examination is a condition of the success of a rescue operation, putting the
preliminary diagnosis and implementing real rescue activities. Delays in a rescue
operation or the lack appropriate the equipment is threatening the patient with
the permanent disability or even a loss of life. It is important so that Teams of
the Medical Rescue, the Aviation emergency ambulance service, individuals of the
State Fire Service and Hospital accident wards have an equipment which will be
compatible. With equipment which without no dilemmas will be used according to
assigning him without anxiety that the use is equaling for loss of possessions or
the exchange on worse or dirty. An next amendment to a bill about the National
Medical rescue should obligatorily have regulations on the availability and
compatibilities of equipment among others used in immobilizing traumatic and the
National Health Fund should develop tough equipment principles in contracting
services. All remarks and amendments to the provisions concerning the
compatibility of equipment used in grudges they will have an intense influence on
the quality of granted benefits in saving the health and the human life as well
as will improve the comfort of the work of the paramedic.
PMID- 27487547
TI - [Lactobacillus fermentum CECT5716 - probiotic from human milk with interesting
properties].
AB - Probiotics are an intensively growing part of the pharmaceutical and nutrition
industries. Along with the intensive development of sales volumes and product
offers, more and more scientific publications on this subject are available (at
the time of writing this article there are available almost 14 thousand
publications in PubMed library). Scientists are trying to find new uses and new
sources for this crucial group of nutrients or potential drugs. At the beginning
of the XXI century it was discovered that the source of probiotics doesn't need
to be only gastrointestinal tract (as previously thought), since they were
obtained from breast milk which for many years were considered to be sterile.
Probiotics from breast milk are an interesting group which could find application
in mastitis, immunity support, infection prevention, infant colics and oral
health. Main representative of this group is a strain of lactic acid bacteria
Lactobacillus fermentum CECT5716.
PMID- 27487549
TI - [Protection of medical personnel in contemporary armed conflicts].
AB - International humanitarian law provides special protection devices and medical
personnel during armed conflicts. In today's wars it became more frequent lack of
respect for the protective emblems of the red cross and red crescent and the lack
of respect for medical activities. The paper presents selected issues of
humanitarian law with a particular emphasis on the rules concerning the
protection of medical services and victims of armed conflicts. All countries that
have ratified the Geneva Conventions and Additional Protocols, are required to
comply in time of war the principles contained in them and their dissemination in
peacetime. Education societies in the field of international humanitarian law can
help to eliminate attacks on medical facilities and personnel and significantly
improve the fate of the victims of armed conflict and mitigate the cruelty of
war. Knowledge of humanitarian law does not prevent further wars, but it can
cause all parties to any armed conflict will abide by its rules during such
activities.
PMID- 27487548
TI - [Amaurosis fugax in inferior wall myocardial infarction with ST segment
elevation].
AB - The patient, a fifty nine year old male, was admitted to the ward with symptoms
of inferior wall myocardial infarction with ST segment elevation combined with
intermittent right side sight loss. Despite typical resting stenocardial chest
pain, ST segment elevation in ECG, transient symptoms of acute heart failure and
slightly elevated myocardial necrosis biomarkers, coronarography did not reveal
obvious source of myocardial ischemia. Moreover, echocardiography did not confirm
decreased ejection fraction. However further research confirmed critical stenosis
of the left internal carotid artery and chronic occlusion of the right internal
carotid artery. Several questions were raised during diagnostic process
including: the cause of cardiac ischemia and the cause of cerebral ischemia.
Clinical data analysis and available literature allowed authors to exclude
cerebral ischemia as a source of ECG ischemic changes and to establish transient
myocardial ischemia causing circulatory decompensation amplified by carotid
arteries atherosclerosis as the source of neurological symptoms.
PMID- 27487550
TI - [Manual therapy in general practice].
AB - The article is devoted to manual therapy practice for diagnostics and treatment
of vertebrogenic pain syndrome in general practice. Analytical roundup of sources
proves medical advantage of implementation of manual therapy basic methods by
general practice specialists.
PMID- 27487551
TI - [Immunohistochemical description of proliferative activity and apoptosis of lung
squamous cell carcinoma (literature review)].
AB - The analysis of the publications are describe immunohistochemical study of
proliferative activity and apoptosis of lung squamous cell carcinoma. Established
that the imbalance between proliferation and cell death is a key process in the
development of tumors. However, the value of tumor markers in histogenesis and
morfogenesis of tumors and forecast their occurrence is not studied enough.
Despite the significant amount of scientific literature devoted to this issue,
has not yet established a clear link expression of immunohistochemical markers of
proliferation and apoptosis with the degree of differentiation of squamous cell
lung cancer. Analysis of the literature shows that the morphology of this
histogenetics type lung cancer at the cellular, subcellular structural and
functional levels are controversial and require detailed investigation.
PMID- 27487552
TI - A novel homozygous mutation causing hereditary tyrosinemia type I in yakut
patient in russia: case report.
AB - INTRODUCTION: Tyrosinemia type 1 (HT1) (OM IM 276700) is an inborn error of
tyrosine catabolism caused be fumarylacetoacetate hedralase deficiency (FAH). In
tyrosinemia type I, dietary therapy and nitisinone (Orfandin(r)), liver
transplantation are effective . AIM: We present here the first report on
identification of FAH mutation in HT1 Yakut patient from Russia with a novel one.
MATERIAL AND METHODS: The material for the clinical study is based on the genetic
data of the patient card with tyrosinemia type 1, which is observed in the
medical-genetic consultations Republican Hospital No1-National Medical Center of
the Republic of Sakha (Yakutia). For molecular genetic analysis has been used
venous whole blood, taken with the written consent from the patient, his
relatives and 200 healthy Yakuts. All regions of the FAH gene spanning exons were
amplified by PCR and mutational analyses was carried out by direct sequencing.
Results of sequencing were confirmed by restriction fragment length polymorphism
(PCR-RELF) analyses. RESULTS: 1 one-year-old child was identified with a
diagnosis hereditary tyrosinemia type Ia, acute form. In exon 13 of the FAH gene
a novel mutation c.1090 G>C (GLu364GLn) in the homozygous state was found in
patient, and in heterozygous state in both parents. The child is treated
Nitisinone therapy. DNA diagnostics of c.1090 G>C mutation frequency in the FAH
gene was conducted using PCR and RFLP analysis in 200 unrelated Yakuts. The
frequency of heterozygous carrier was 1.0%.
PMID- 27487553
TI - [Clinical and morphological observation of purulent iliopsoitis].
AB - The article describes the modern literary data on classification, etiology,
pathogenesis and predisposing factors in the development of purulent iliopsoitis.
Where are clinical and morphological analysis of five deaths cases of purulent
ileopsoitis. On the basis of these studies found that purulent ileopsoitis that
occur in middle and old age, are more common in women, can be either unilateral
or bilateral localization. Purulent ileopsoitis arises by forming abscess in the
iliopsoas muscle. Primary ileopsoitis arises in connection with injuries gluteal
and lumbar region. Secondary ileopsoit developed as a complication of
inflammatory and neoplastic processes, with an initial mechanism for the
development of the pathological process were necrotic changes in the external
iliac lymph nodes. In vivo it is difficult to diagnose, that's why is necessary
to apply a comprehensive study, including clinical data, anamnesis, general
clinical and laboratory parameters, instrumental methods.
PMID- 27487554
TI - Aspects of public health within accreditation of public healthcare management
specialists in ukraine and russia in the late 18th - early 19th century
(dedicated to the 250th anniversary of a prominent professor Mukhin E.O.).
AB - Public healthcare management and supply of qualified medical personnel attained
state significance in the early 19th century, the issue to be regulated by
special and general law regulations. Public health promotion was the duty of
medical authorities, which required professional training in this branch. The
article contains the requirements for the employers' knowledge and skills in the
mentioned area of medicine. The author reveals the main questions which medical
authorities were concerned with and the main requirements for academic
examinations.
PMID- 27487555
TI - [Shame of having a disabled child].
AB - This work is devoted to the problem of shame linked to disability in children. It
has been inspired by patients - disabled infants and their parents. The shame
evidently experienced during meetings with parents learning about their child's
condition leads to many difficult questions. Shame is not a simple, isolated
emotion. It is a complicated feeling, closely connected to various shame-related
emotions and experiences. Shame leads to a sense of guilt and self-blame. Shame
linked to a child's disability is a shame of 'lacking' and low self-esteem.
Additionally it is feeling of nakedness, vulnerability and despoilment of
intimacy; it makes parents feel forced to put their interior world on display and
to show their weakness caused by their child's condition. Sometimes shame is an
experience of humiliation, or hurt dignity caused by the looks of other people.
It is also the shame of one's own difficult thoughts, desire to escape
responsibility. It is being ashamed of experiencing shame. It is an emotion of
ultimate suffering, often returning during whole life. One solution to the
'discomfort of birth' could be a lonely island. The issue is not that simple,
however, and philosophy helps in this respect. A being is good and it has to be
good. One cannot be someone, one is not. This is the difference between a being
and a desire. There is love and acceptance, but there is also shame - even on a
lonely island.
PMID- 27487556
TI - Conformal BaTiO3 Films with High Piezoelectric Coupling through an Optimized
Hydrothermal Synthesis.
AB - Two-dimensional (2D) ferroelectric films have vast applications due to their
dielectric, ferroelectric, and piezoelectric properties that meet the
requirements of sensors, nonvolatile ferroelectric random access memory (NVFeRAM)
devices, and micro-electromechanical systems (MEMS). However, the small surface
area of these 2D ferroelectric films has limited their ability to achieve higher
memory storage density in NVFeRAM devices and more sensitive sensors and
transducer. Thus, conformally deposited ferroelectric films have been actively
studied for these applications in order to create three-dimensional (3D)
structures, which lead to a larger surface area. Most of the current methods
developed for the conformal deposition of ferroelectric films, such as metal
organic chemical vapor deposition (MOCVD) and plasma-enhanced vapor deposition
(PECVD), are limited by high temperatures and unstable and toxic organic
precursors. In this paper, an innovative fabrication method for barium titanate
(BaTiO3) textured films with 3D architectures is introduced to alleviate these
issues. This fabrication method is based on converting conformally grown rutile
TiO2 nanowire arrays into BaTiO3 textured films using a simple two-step
hydrothermal process which allows for thickness-controlled growth of conformal
films on patterned silicon wafers coated with fluorine-doped tin oxide (FTO).
Moreover, the processing parameters have been optimized to achieve a high
piezoelectric coupling coefficient of 100 pm/V. This high piezoelectric response
along with high relative dielectric constant (epsilonr = 1600) of the conformally
grown textured BaTiO3 films demonstrates their potential application in sensors,
NVFeRAM, and MEMS.
PMID- 27487557
TI - Attacks Intended to Seriously Harm and Co-occurring Drug Use Among Youth in the
United States.
AB - BACKGROUND: While it is known that substance use and violence co-occur, less is
understood in terms of how this relationship might vary based on the degree of
youth involvement in violence. OBJECTIVES: This study sought to examine the
prevalence and degree that substance use disorders (SUD) and related
intrapersonal and contextual factors were associated with violent attacks.
METHOD: Repeated cross-sectional data from a population-based study (National
Survey on Drug Use and Health) of youth ages 12-17 (n = 216,852) in the United
States between 2002 and 2013 were pooled to increase the analytic sample size.
Survey multinomial regression was used to examine psychosocial and substance use
differences between youth reporting episodic (1-2 times, n = 13,091; 5.84%) and
repeated violent attacks (3+ times, n = 1,819; 0.83%) in contrast with youth
reporting no attacks. Additional analyses examined the association of
sociodemographic, intrapersonal, and contextual factors with SUD among youth
reporting violent attacks. RESULTS: The prevalence of SUD among youth with no
attacks was 6% compared to 22% among episodic and 36% among repeatedly violent
youth. Violence-involved youth were substantially more likely to experience
elevated sensation-seeking, easy drug access, and recent drug offers and less
likely to benefit from religiosity and protective substance use beliefs.
CONCLUSIONS/IMPORTANCE: Findings highlight the importance of distinguishing
between the various gradations of violence among youth in understanding the
relationship between substance use and violence, and shed light on the
intrapersonal and contextual factors that can help identify violent youth at
greatest risk for substance use problems.
PMID- 27487558
TI - BRM polymorphisms, pancreatic cancer risk and survival.
AB - Variant alleles of two promoter polymorphisms in the BRM gene (BRM-741, BRM
1321), create MEF2D transcription binding sites that lead to epigenetic silencing
of BRM, the key catalytic component of the SWI/SNF chromatin remodeling complex.
BRM suppression can be reversed pharmacologically.(1) Our group and others have
reported associations with lung, head and neck, hepatocellular cancer risk,(1-3)
and with lung and esophageal cancer prognosis (ASCO 2013; abstract 11057 & 4077).
Herein, we assessed risk and survival associations with pancreatic cancer. A
provincial population-based case-control study was conducted with 623
histologically confirmed pancreatic adenocarcinoma cases and 1,192 age/gender
distribution-matched controls.(4) Survival of cases was obtained through the
Ontario Cancer Registry. Logistic and Cox proportional hazard regression models
were fitted, adjusting for relevant covariates. Median age was 65 y; 52% were
male; Stage I (8%), II (55%), III (14%), IV (23%); 53% after curative resection,
79% after chemotherapy; and 83% had died. In the risk analysis, adjusted odds
ratios (aOR) were 1.01 (95% CI: 0.1-2.0) and 0.96 (95% CI: 0.7-1.3) for the
homozygotes of BRM-741 and BRM-1321, respectively; aOR of double-homozygotes was
1.11 (95% CI: 0.80-1.53), compared to the double-wildtype. For the survival
analysis, adjusted hazard ratios (aHR) were 2.19 (95% CI: 1.9-2.5) for BRM-741
and 1.94 (95% CI: 1.7-2.2) for BRM-1321, per unit increase in variant alleles.
Compared with the double-wildtype, aHR for carrying no, one, and two double
homozygotes were 2.14 (95% CI: 1.6-2.8), 4.17 (95% CI: 3.0-5.7), 8.03 (95% CI:
5.7-11.4), respectively. In conclusion, two functional promoter BRM polymorphisms
were not associated with pancreatic adenocarcinoma risk, but are strongly
associated with survival.
PMID- 27487559
TI - Evaluation of efficacy and biocompatibility of a new absorbable synthetic
substitute as a dural onlay graft in a large animal model.
AB - BACKGROUND: Numerous dura substitutes are commercially available, but no
absorbable synthetic dura repair product has been used for both onlay and suture
applications. OBJECTIVE: The safety and effectiveness of a new absorbable
synthetic substitute composed of Poly-L-lactide microfibers as onlay dural graft
were evaluated. METHODS: Physical properties and performance of the microfibrous
synthetic dural substitute implanted as an onlay or suturable grafts were
compared with these commercial products, including CODMAN ETHISORBTM Dura Patch
and DuraGenTM Dural Graft Matrix, in a canine duraplasty model. The cerebrospinal
fluid (CSF) leakage, macroscopic and microscopic observation at 30 and 90 days
after implantation were investigated. RESULTS: The absorbable synthetic dural
substitute exhibited good wettability and conformability. When implanted as an
onlay graft, it can prevent CSF leakage and integrate with the surrounding tissue
to repair dural defects, indicating its good efficacy and biocompatibility as an
onlay graft. CONCLUSION: Based on the excellent physical properties and
performances mentioned above, the new absorbable synthetic substitute can be
applied as a dural graft for both onlay and suturable applications.
PMID- 27487560
TI - Correction to Tetrahydroisoquinoline-Derived Urea and 2,5-Diketopiperazine
Derivatives as Selective Antagonists of the Transient Receptor Potential
Melastatin 8 (TRPM8) Channel Receptor and Antiprostate Cancer Agents.
PMID- 27487561
TI - Spatial tuning and brain state account for dorsal hippocampal CA1 activity in a
non-spatial learning task.
AB - The hippocampus is a brain area crucial for episodic memory in humans. In
contrast, studies in rodents have highlighted its role in spatial learning,
supported by the discovery of place cells. Efforts to reconcile these views have
found neurons in the rodent hippocampus that respond to non-spatial events but
have not unequivocally dissociated the spatial and non-spatial influences on
these cells. To disentangle these influences, we trained freely moving rats in
trace eyeblink conditioning, a hippocampally dependent task in which the animal
learns to blink in response to a tone. We show that dorsal CA1 pyramidal neurons
are all place cells, and do not respond to the tone when the animal is moving.
When the animal is inactive, the apparent tone-evoked responses reflect an
arousal-mediated resumption of place-specific firing. These results suggest that
one of the main output stages of the hippocampus transmits only spatial
information, even in this non-spatial task.
PMID- 27487562
TI - Phosphorus removal performance and population structure of phosphorus
accumulating organisms in HA-A/A-MCO sludge reduction process.
AB - We developed a new sludge reduction HA-A/A-MCO (Hydrolysis-Acidogenosis
Anaerobic/Anoxic -Multistep Continuous Oxic tank) process, which has improved
phosphate (P) and nitrogen (N) removal. Its biological treatment unit uses an
A2/O P & N removal process with hydrolysis acidification, multistep continuous
aeration, and continuous flow, coupled with sidestream P removal by draining out
anaerobic P-bearing wastewater. The process has advanced synchronization of P and
N removal and sludge reduction. The improved performance is closely associated
with the population structure of P-accumulating organisms (PAOs). This study
investigated the relationship between P removal performance and the population
structure of PAOs. The results show that the average effluent P content of HA-A/A
MCO process was only 0.44 mg/L, when the influent P concentration was 8~12 mg/L.
The effluent met the A standard set by GB18918-2002. PAOs were able to
effectively release 1 mg of P and absorb 2.8 mg of P. The system removed P by
draining out anaerobic P-rich wastewater, as P had been reduced in the aerobic
absorption process. This reduced the need for excess P uptake ability of the
PAOs. The bacterial pure culture method was applied to isolate 5 PAOs with
typical P absorption and removel features. 16SrDNA amplification and sequence
analysis revealed that Acinetobacter sp. and Lampropedia sp played dominant roles
in anaerobic P-releasing process. Moreover, Devosia sp. and Bdellovibrio sp were
the primary strains in the aerobic tank, and, they were the major stains for P
absorption. Uncultured Bacterium and other uncultured strains were detected in
the anoxic tank.
PMID- 27487563
TI - The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma
cell apoptotic death.
AB - Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus
L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro
(mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs
have been identified to participate in regulating glioma development. However, no
studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting
in glioma cell death. This study investigated the effects of XN-mediated miRNA
expression in activating apoptotic pathways in glioblastoma U87 MG cells. First,
we found that XN significantly reduced cell viability and induced apoptosis via
pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We
also identified that pro-caspase-9 cleavage, Bcl2 family expression changes,
mitochondrial dysfunction, and intracellular ROS generation also participated in
XN-induced glioma cell death. With a microarray analysis, miR-204-3p was
identified as the most upregulated miRNA induced by XN cytotoxicity. The
extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to
participate in XN-upregulated miR-204-3p expression. With a promoter assay and
ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene
promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell
lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell
apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was
validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's
inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a
critical role in mediating glioma cell death. These results emphasized that the
XN-mediated miR-204-3p network may provide novel therapeutic strategies for
future glioblastoma therapy and drug development.
PMID- 27487564
TI - Dihydromyricetin suppresses inflammatory responses in vitro and in vivo through
inhibition of IKKbeta activity in macrophages.
AB - Dihydromyricetin (DMY) a flavonoid derived from medicinal plant Ampelopsis
grossedentata, possesses anti-oxidative and anti-inflammatory effects in vitro,
however, the in vivo anti-inflammatory action of DMY remains unknown. In the
current study, carrageenan-induced paw edema in rat, an acute inflammation model,
and RAW264.7 macrophages activated by LPS were employed to evaluate the anti
inflammatory potency of DMY in vivo and in vitro. Results showed that DMY
significantly attenuated rat paw edema induced by carrageenan. Also, DMY markedly
inhibited NO secretion, iNOS, and COX-2 protein expression, as well as p65
phosphorylation via suppression of IKKbeta activity and IKKalpha/beta
phosphorylation in RAW264.7 cells. And using high resolution Atomic Force
Microscope (AFM), we also proved that DMY prevented morphological change and
membrane alterations of RAW 264.7 macrophages caused by LPS stimulation. As
activation of macrophages is one of major factors in carrageenan-induced paw
edema of rats, the anti-inflammatory action of DMY is suggested to be closely
associated with suppression of macrophage activation. These findings indicate
that DMY is valuable of being further investigated as a candidate new agent for
treating inflammatory conditions, and suggest that AFM could be a powerful
nanotool for anti-inflammatory investigations. SCANNING 38:901-912, 2016. (c)
2016 Wiley Periodicals, Inc.
PMID- 27487565
TI - Synthesis and pharmacological characterization of novel N-(trans-4-(2-(4
(benzo[d]isothiazol-3-yl)piperazin-1-yl)ethyl)cyclohexyl)amides as potential
multireceptor atypical antipsychotics.
AB - A series of novel benzisothiazolylpiperazine derivatives combining potent
dopamine D2 and D3, and serotonin 5-HT1A and 5-HT2A receptor properties were
synthesized and evaluated for their potential antipsychotic properties. The most
promising derivative was 9j. The unique pharmacological features of 9j were a
high affinity for D2, D3, 5-HT1A, and 5-HT2A receptors, together with a 20-fold
selectivity for the D3 versus D2 subtype, and a low affinity for muscarinic M1
(reducing the risk of anticholinergic side effects), and for hERG channels
(reducing incidence of QT interval prolongation). In animal behavioral models, 9j
inhibited the locomotor-stimulating effects of phencyclidine, blocked conditioned
avoidance response, and improved the cognitive deficit in the novel object
recognition tests in rats. 9j exhibited a low potential for catalepsy, consistent
with results with risperidone. In addition, favorable brain penetration of 9j in
rats was detected. These studies have demonstrated that 9j is a potential
atypical antipsychotic candidate.
PMID- 27487566
TI - alpha-N-heterocyclic thiosemicarbazone Fe(III) complex: Characterization of its
antitumor activity and identification of anticancer mechanism.
AB - We synthesized an alpha-N-heterocyclic thiosemicarbazone ligand (L) and its Fe
complex (C1) and assessed their chemical and biological properties in order to
understand their marked activity. Electrochemical studies and ascorbate oxidation
studies demonstrated that C1 shows considerable redox activity, and Fe(III/II)
redox potentials was within the range accessible to cellular oxidants and
reductants. Absorption spectral, emission spectral and viscosity analysis reveal
that L and C1 interacted with DNA through intercalation and C1 exhibited a higher
DNA binding ability. Agarose gel electrophoresis experiments indicated that C1
exhibited the highest pBR322 DNA cleaving ability. In vitro, C1 showed
significantly more anticancer activity than the ligand alone. Moreover, C1
induces production of reactive oxygen species (ROS) and DNA damage, resulting in
activation of the p53 pathway, cell cycle arrest at the S phase, and mitochondria
mediated apoptosis by regulating the expression of Bcl-2 family proteins.
PMID- 27487567
TI - Inhibitory activity evaluation and mechanistic studies of tetracyclic oxindole
derivatives as alpha-glucosidase inhibitors.
AB - alpha-Glucosidase inhibitors are known to prevent the digestion of carbohydrates
and reduce the impact of carbohydrates on blood glucose. Three series of
tetracyclic oxindole derivatives were designed, synthesized and evaluated for
alpha-glucosidase inhibitory activity in vitro. Compound 6t exhibited the most
potent inhibitory activity with IC50 0.7 MUM and was about 170 times as active as
acarbose (IC50 = 115.8 MUM). The kinetic analysis of compound 6t revealed it
inhibited alpha-glucosidase in an irreversible and mixed manner. Fluorescence
spectra indicated that 6t directly bound to alpha-glucosidase. Docking simulation
showed the existence of potential H-bonding, van der Waals, Pi and Sigma-Pi
interactions between 6t and alpha-glucosidase.
PMID- 27487568
TI - Design, synthesis, anticancer, antimicrobial activities and molecular docking
studies of theophylline containing acetylenes and theophylline containing 1,2,3
triazoles with variant nucleoside derivatives.
AB - A new series of theophylline containing acetylene derivatives (6a-6b and 7-13)
and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives
(20-32) have been designed and synthesized. These compounds were screened for
anticancer and antimicrobial activity. Further the computational docking and 2D
QSAR were performed using MOE software to identify novel scaffolds. The results
showed that compound 29 and 30 exhibit significant cytotoxic effect on all four
cancer cells such as lung (A549), colon (HT-29), breast (MCF-7) and melanoma
(A375) with IC50 values of 2.56, 2.19, 1.89, 4.89 MUM and 3.57, 2.90, 2.10, 5.81
MUM respectively. Whereas quite different results were observed for these
compounds in antimicrobial studies. Compounds 11, 21 and 26 have exhibited
significant minimum inhibitory concentrations (MIC) against Staphylococcus
aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The docking
studies demonstrate that compound 27, 28, 29 and 30 have good dock score and
binding affinities with various therapeutic targets in cancer cell proliferation.
In addition these compounds have shown acceptable correlation with bioassay
results in the regression plots generated in 2D QSAR models. This is the first
report to demonstrate the theophylline containing acetylene derivatives and
theophylline containing 1,2,3-triazole nucleoside hybrids as potential anticancer
and antimicrobial agents with comprehensive in silico analysis.
PMID- 27487569
TI - Design and synthesis of 1,2,3-triazole-containing N-acyl zanamivir analogs as
potent neuraminidase inhibitors.
AB - The design of potent metabolically stable neuraminidase (NA) inhibitors
represents an attractive approach for treating influenza virus infection. In this
study, we describe the exploitation of the 150-cavity in the active site of group
1 NA for the design, synthesis, and in vitro evaluation of new triazole
containing N-acyl derivatives related to Zanamivir. Inhibition studies with
influenza virus NAs of group 1 (H1N1) and group 2 (H3N2) revealed that several of
them are good inhibitors, with IC50 values in the low nanomolar (2.3 nM-31 nM)
range. Substituents that form stable van der Waals interaction with the 150
cavity residues play crucial roles in NA inhibition as demonstrated by the
potency of 6a (H1N1 IC50 = 2.3 nM, and H3N2 IC50 = 2.9 nM). Docking studies
indicated that the cyclohexane-substituted triazole ring extended toward the
hydrophobic region in the active site of group 1 NA in open form. The high
potency observed for inhibitor 6a may be attributable to the highly favorable
hydrophobic interactions in this region.
PMID- 27487570
TI - Chalcogen containing heterocyclic scaffolds: New hybrids with antitumoral
activity.
AB - In this work, 27 novel hybrid derivatives containing diverse substituents with
chalcogen atoms (selenium or sulfur) and several active heterocyclic scaffolds
have been synthesized. Compounds were tested against two human cancer cells lines
(MCF7 and PC-3) and a normal human mammary epithelial cell line (184B5) in order
to determine their activity and selectivity against malignant cells. Ten
compounds showed GI50 values below 10 MUM in at least one of the cancer cell
lines and six of them exhibited a selectivity index higher than 9. In general,
selenium-containing compounds were more active than their corresponding sulfur
analogs but we found some thiocyanate derivatives with comparable or higher
activity and selectivity. Among the different substituents, the seleno- and thio
cyanate groups showed the most promising results. On the basis of their potent
activity and high selectivity index, compounds 7e and 8f (containing a
thiocyanate and a selenocyanate group, respectively) were selected for further
biological evaluation. Both the compounds induced caspase-dependent cell death
and cell cycle arrest in G2/M phase. In addition, these compounds do not violate
any of the Lipinski's Rule of Five and thus possess good potential to become
drugs, compound 7e being particularly promising.
PMID- 27487571
TI - Comparison of anti-OJ antibody detection assays between an immunoprecipitation
assay and line blot assay.
PMID- 27487572
TI - Clinical features and prognosis of patients with myelodysplastic syndromes who
were exposed to atomic bomb radiation in Nagasaki.
AB - There is evidence that radiation exposure is a causative factor of
myelodysplastic syndromes (MDS). However, little is known about whether radiation
exposure is also a prognostic factor of MDS. We investigated the impact of
radiation exposure on the prognosis of MDS in Nagasaki atomic bomb survivors
using the International Prognostic Scoring System (IPSS) and the revised version
(IPSS-R). Subjects were 140 patients with primary MDS diagnosed between 1985 and
2011 and evaluable for IPSS, IPSS-R, and exposure distance. Of those, 31 were
exposed at <1.5 km, 35 at 1.5-2.99 km, and 74 at >=3.0 km. By the end of March
2014, 47 patients (34%) progressed to overt leukemia and 106 (75.7%) died. By
comparing with patients exposed at >=3.0 km, those exposed at <1.5 km had
significantly higher frequencies of abnormal chromosome (P = 0.02),
intermediate/poor IPSS, and intermediate/poor/very poor IPSS-R cytogenetic
category (P = 0.0001, and P < 0.0001, respectively). As with de novo MDS,
multivariate Cox regression analyses revealed that cytogenetic abnormalities,
IPSS karyotype, and IPSS-R cytogenetics were significantly associated with poor
survival, and cumulative incidence of leukemic transformation in MDS among atomic
bomb survivors, but exposure distance was not associated with any poor outcomes.
These suggest that exposure to the greater dose of atomic bomb radiation is
associated with developing poor cytogenetic abnormalities in MDS, which might
consequently lead to overt leukemia among atomic bomb survivors.
PMID- 27487574
TI - Bacterial magnetic nanoparticles for photothermal therapy of cancer under the
guidance of MRI.
AB - The bacterial magnetic nanoparticles (BMPs) are biomineralized by the
magnetotactic bacteria and naturally covered with a layer of biomembrane. Herein,
BMPs were isolated and firstly used for the photothermal therapy (PTT) of cancer
under the guidance of magnetic resonance imaging (MRI) in vitro and in vivo. The
results showed that BMPs could rapidly convert the energy of 808 nm near-infrared
(NIR) light into heat. After internalization by the HepG2 tumor cells, BMPs with
good biocompatibility could induce an efficient killing effect after NIR light
irradiation, along with a change of mitochondrial membrane potential (DeltaPsim)
and level of intracellular reactive oxygen species (ROS). The in vivo therapy
also confirms that PTT with BMPs could effectively and completely ablate the
tumor in mice without inducing observable toxicity. T2-weighted MRI showed a
clear tumor boundary and a 25% enhancement of negative contrast enhancement at
the tumor site, suggesting that BMPs can act as an effective MRI contrast agent
for guiding the PTT. Our results indicate that BMPs could be a potential
theranostic agent for simultaneous MRI and PTT of cancer.
PMID- 27487573
TI - Comparative Effectiveness of Cognitive Therapy and Dynamic Psychotherapy for
Major Depressive Disorder in a Community Mental Health Setting: A Randomized
Clinical Noninferiority Trial.
AB - IMPORTANCE: Dynamic psychotherapy (DT) is widely practiced in the community, but
few trials have established its effectiveness for specific mental health
disorders relative to control conditions or other evidence-based psychotherapies.
OBJECTIVE: To determine whether DT is not inferior to cognitive therapy (CT) in
the treatment of major depressive disorder (MDD) in a community mental health
setting. DESIGN, SETTING, AND PARTICIPANTS: From October 28, 2010, to July 2,
2014, outpatients with MDD were randomized to treatment delivered by trained
therapists. Twenty therapists employed at a community mental health center in
Pennsylvania were trained by experts in CT or DT. A total of 237 adult
outpatients with MDD seeking services at this site were randomized to 16 sessions
of DT or CT delivered across 5 months. Final assessment was completed on December
9, 2014, and data were analyzed from December 10, 2014, to January 14, 2016.
INTERVENTIONS: Short-term DT or CT. MAIN OUTCOMES AND MEASURES: Expert blind
evaluations with the 17-item Hamilton Rating Scale for Depression. RESULTS: Among
the 237 patients (59 men [24.9%]; 178 women [75.1%]; mean [SD] age, 36.2 [12.1]
years) treated by 20 therapists (19 women and 1 man; mean [SD] age, 40.0 [14.6]
years), 118 were randomized to DT and 119 to CT. A mean (SD) difference between
treatments was found in the change on the Hamilton Rating Scale for Depression of
0.86 (7.73) scale points (95% CI, -0.70 to 2.42; Cohen d, 0.11), indicating that
DT was statistically not inferior to CT. A statistically significant main effect
was found for time (F1,198 = 75.92; P = .001). No statistically significant
differences were found between treatments on patient ratings of treatment
credibility. Dynamic psychotherapy and CT were discriminated from each other on
competence in supportive techniques (t120 = 2.48; P = .02), competence in
expressive techniques (t120 = 4.78; P = .001), adherence to CT techniques (t115 =
-7.07; P = .001), and competence in CT (t115 = -7.07; P = .001). CONCLUSIONS AND
RELEVANCE: This study suggests that DT is not inferior to CT on change in
depression for the treatment of MDD in a community mental health setting. The 95%
CI suggests that the effects of DT are equivalent to those of CT. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT01207271.
PMID- 27487575
TI - Comparison of trout hepatocytes and liver S9 fractions as in vitro models for
predicting hepatic clearance in fish.
AB - Isolated hepatocytes and liver S9 fractions have been used to collect in vitro
biotransformation data for fish as a means of improving modeled estimates of
chemical bioaccumulation. To date, however, there have been few direct
comparisons of these 2 methods. In the present study, cryopreserved trout
hepatocytes were used to measure in vitro intrinsic clearance rates for 6
polycyclic aromatic hydrocarbons (PAHs). These rates were extrapolated to
estimates of in vivo intrinsic clearance and used as inputs to a well stirred
liver model to predict hepatic clearance. Predicted rates of hepatic clearance
were then evaluated by comparison with measured rates determined previously using
isolated perfused livers. Hepatic clearance rates predicted using hepatocytes
were in good agreement with measured values (<2.1-fold difference for 5 of 6
compounds) under 2 competing binding assumptions. These findings, which may be
attributed in part to high rates of PAH metabolism, are similar to those obtained
previously using data from liver S9 fractions. For 1 compound (benzo[a]pyrene),
the in vivo intrinsic clearance rate calculated using S9 data was 10-fold higher
than that determined using hepatocytes, possibly due to a diffusion limitation on
cellular uptake. Generally, however, there was good agreement between calculated
in vivo intrinsic clearance rates obtained using either in vitro test system.
These results suggest that both systems can be used to improve bioaccumulation
assessments for fish, particularly when vitro rates of activity are relatively
high, although additional work is needed to determine if the chemical domain of
applicability for each system differs. Environ Toxicol Chem 2017;36:463-471.
Published 2016 SETAC. This article is a US government work and, as such, is in
the public domain in the United States of America.
PMID- 27487576
TI - Data fusion of near-infrared and mid-infrared spectra for identification of
rhubarb.
AB - Rhubarb has different medicinal efficacy to official rhubarb and may affect the
clinical medication safety. In order to guarantee the quality of rhubarb, we
established a method to distinguish unofficial rhubarbs. 52 official and
unofficial rhubarb samples were analyzed using near-infrared (NIR) spectroscopy
and mid-infrared (MIR) spectroscopy for classification. The feature vectors,
which were selected by wavelet compression (WC) and interval partial least
squares (iPLS) from NIR, MIR spectra, were fused together for identifying rhubarb
samples. Partial least squares-discriminant analysis (PLS-DA), soft independent
modeling of class analogies (SIMCA), support vector machine (SVM) and artificial
neural network (ANN) were compared for classifying rhubarb. The use of data
fusion strategies improved the classification model and allowed correct
classification of all the samples.
PMID- 27487577
TI - Impact of Fe on structural modification and room temperature magnetic ordering in
BaTiO3.
AB - Ba1-xFexTiO3 (x=0, 0.005, 0.01) polycrystalline ceramics are prepared using solid
state reaction method. Structural studies through XRD, Raman and XPS confirm
single tetragonal phase for BaTiO3 whereas a structural disorder tends to
intervene with the introduction of smaller Fe ions which reduces the tolerance
factor and tetragonality ratio. Grain size of the samples is estimated using SEM
micrographs with ImageJ software and chemical composition is confirmed using EDX
spectra. Raman spectra measured in the temperature range of 303K to 573K showers
light on the structural phase transition exploiting a significant disappearance
of the 306cm-1 mode. Further, structural analyses suggest the entry of Fe into
the B-site upon increasing its concentration in BaTiO3. The dopant sensitive
modes lying at around 640cm-1 and 650cm-1 are assigned to lattice strain. A
reduction in ferroelectric to paraelectric transition temperature is observed
with a transformation from diffused type to normal ferroelectric upon the
increased Fe content. The oxidation state of Fe in the BaTiO3 lattice has been
decided using EPR Spectra precisely. Room temperature magnetic ordering is
observed in Fe substituted BaTiO3 using PPMS. The coexistence of ferroelectric
and magnetic ordering is established in the present study for optimized Fe
substituted BaTiO3.
PMID- 27487578
TI - Terbinafine inhibits gap junctional intercellular communication.
AB - Terbinafine is an antifungal agent that selectively inhibits fungal sterol
synthesis by blocking squalene epoxidase. We evaluated the effect of terbinafine
on gap junctional intercellular communication (GJIC). Fluorescence recovery after
photobleaching (FRAP) and I-YFP GJIC assays revealed that terbinafine inhibits
GJIC in a reversible and dose-dependent manner in FRT-Cx43 and LN215 cells.
Treatment with terbinafine did not affect Cx43 phosphorylation status or
intracellular Ca(2+) concentration, well-known action mechanisms of various GJIC
blockers. While a structurally related chemical, naftifine, attenuated GJIC,
epigallocatechin gallate, another potent squalene epoxidase inhibitor with a
different structure, did not. These results suggest that terbinafine inhibits
GJIC with a so far unknown mechanism of action.
PMID- 27487579
TI - Extension of Expiration Dates for Four Body System Listings. Final rule.
AB - We are extending the expiration dates of the following body systems in the
Listing of Impairments (listings) in our regulations: Musculoskeletal System,
Cardiovascular System, Digestive System, and Skin Disorders. We are making no
other revisions to these body systems in this final rule. This extension ensures
that we will continue to have the criteria we need to evaluate impairments in the
affected body systems at step three of the sequential evaluation processes for
initial claims and continuing disability reviews.
PMID- 27487580
TI - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of
the Provider Enrollment Moratoria Access Waiver Demonstration of Part B Non
Emergency Ground Ambulance Suppliers and Home Health Agencies in Moratoria
Designated Geographic Locations. Implementation of the waiver demonstration.
AB - This notice announces the Provider Enrollment Moratoria Access Waiver
Demonstration of Part B Non-Emergency Ground Ambulance Suppliers and Home Health
Agencies in 6 states. The demonstration is being implemented in accordance with
section 402 of the Social Security Amendments of 1967 and gives CMS the authority
to grant waivers to the statewide enrollment moratoria on a case-by-case basis in
response to access to care issues, and to subject providers and suppliers
enrolling via such waivers to heightened screening, oversight, and
investigations.
PMID- 27487581
TI - Medicare, Medicaid, and Children's Health Insurance Programs: Announcement of
the Implementation and Extension of Temporary Moratoria on Enrollment of Part B
Non-Emergency Ground Ambulance Suppliers and Home Health Agencies in Designated
Geographic Locations and Lifting of the Temporary Moratoria on Enrollment of Part
B Emergency Ground Ambulance Suppliers in All Geographic Locations. Extension,
implementation, and lifting of temporary moratoria.
AB - This document announces the extension of temporary moratoria on the enrollment of
new Medicare Part B non-emergency ground ambulance suppliers and Medicare home
health agencies (HHAs), subunits, and branch locations in specific locations
within designated metropolitan areas in Florida, Illinois, Michigan, Texas,
Pennsylvania, and New Jersey to prevent and combat fraud, waste, and abuse. It
also announces the implementation of temporary moratoria on the enrollment of new
Medicare Part B non-emergency ground ambulance suppliers and Medicare HHAs,
subunits, and branch locations in Florida, Illinois, Michigan, Texas,
Pennsylvania, and New Jersey on a statewide basis. In addition, it announces the
lifting of the moratoria on all Part B emergency ground ambulance suppliers.
These moratoria, and the changes described in this document, also apply to the
enrollment of HHAs and non-emergency ground ambulance suppliers in Medicaid and
the Children's Health Insurance Program.
PMID- 27487582
TI - Leadership Development in Dental Education: Report on the ADEA Leadership
Institute, 2000-14.
AB - The American Dental Education Association's Leadership Institute (ADEA LI) is the
association's flagship development program for those aspiring to leadership in
dental and higher education. As with previous studies of the ADEA LI, ADEA will
use information from the survey described in this report to improve the ADEA LI
curriculum and to guide other leadership development efforts. In 2014-15, ADEA
distributed a 50-item online survey via email to all ADEA LI alumni from the
classes of 2000 through 2014. The survey included selected-response questions,
closed-ended questions, and open-response questions. The survey had an overall
response rate of 47% (133/285); response rates to individual items varied. The
mean age of the respondents when they participated in the Institute was 48.5
years. Men and women were almost equally represented among the respondents.
Nearly half reported their ultimate career goal as department chair, associate
dean, or assistant dean, while 20 (15.8%) indicated a goal of becoming dean and
15 (11.8%) aspired to administrative roles higher than dean. Areas the
respondents recommended for improvement included more programming in budgeting
and financial management, fundraising, and personnel management. Almost 100% of
the respondents indicated they would recommend the ADEA LI to others. Overall,
the survey respondents confirmed the value of the ADEA LI in their assessment of
their fellowship and its subsequent application to their careers. Comparison of
elements from this study to previous studies of ADEA LI alumni demonstrates the
effectiveness of past changes made to the Institute and the creation of
additional ADEA leadership initiatives.
PMID- 27487583
TI - [Not Available].
PMID- 27487584
TI - [Commentary for Guest Editorial: Mario Maj: 21st century psychiatry: The need for
a unified framework].
PMID- 27487585
TI - [90 years from the date of a birth].
PMID- 27487586
TI - [85 years from the date of a birth].
PMID- 27487587
TI - [70 years from the date of a birth].
PMID- 27487588
TI - [70 years from the date of a birth].
PMID- 27487589
TI - THE PREDICTIVE VALUE OF SERUM URIC ACID FOR THE OCCURRENCE, SEVERITY AND OUTCOMES
OF PRE-ECLAMPSIA AMONG PARTURIENTS AT NNEWI, NIGERIA.
AB - OBJECTIVE: To determine the predictive value of serum uric acid for preeclampsia,
its severity and pregnancy outcome. METHODS: This is a cohort study that was
performed on normal pregnant women attending antenatal clinic at Nnamdi Azikiwe
University Teaching Hospital Nnewi Nigeria. Serum uric acid was determined in 200
women attending antenatal clinic between the gestational ages of 14 and 26 weeks.
The women were followed up at 2 weekly intervals until 36 weeks and weekly
thereafter until delivery. Women who developed pre-eclampsia or eclampsia were
identified. Pregnancy outcomes were determined as well as fetal and placental
weights. The data was analised with SPSS version 16.0. The chi square was used
for test of significance. The positive and negative predictive values were
determined. RESULTS: A total of 200 normal pregnant women were recruited for the
study. Nine of them were lost to follow up. Subsequently, 10.5% of the women
developed preeclampsia. The positive and negative predictive values of serum uric
acid for preeclampsia were 78.9% and 97.1%, respectively. CONCLUSION: Serum uric
acid was found to be a useful predictor of the occurrence of preeclampsia and its
severity.
PMID- 27487590
TI - SPUTUM SMEAR PATTERN AMONG PATIENTS DIAGNOSED WITH PULMONARY TUBERCULOSIS IN
MAKURDI, NORTH CENTRAL NIGERIA.
AB - BACKGROUND: Tuberculosis (TB) is endemic in Nigeria due mainly to the high burden
of HIV/AIDS and especially in Benue state which has the highest prevalence of HIV
in Nigeria. Sputum smear examination is of importance in the diagnosis of
pulmonary TB and can be smear-positive or negative. In this study, we analyzed
the sputum smear results of all patients diagnosed to have PTB during the time
under review. METHODS: The study was a retrospective study done with records of
patients diagnosed with PTB between July 2009 and July 2011. The sample size was
305. AIM: To determine the smear patterns in pulmonary tuberculosis and its
relationship with HIV status. RESULTS: There was slight male preponderance among
the study group. 37% were found to be smear positive, out of which 63.7% and
36.3% were males and females respectively. The highest frequency was between 21
40 years and in this age group there were more males than females.72.1%
wereTB/HIV co-infected and 29.1% of the TB/HIV co-infected patients had smear
positiveTuberculosis. CONCLUSION: There is a high burden of TB/HIV co-infection
affecting predominantly the youths. Sputum smear results in TB/HIV co-infection
are largely negative. There is the need for provision of other diagnostic tests
to improve the diagnosis of TB in our environment and targeted intervention among
the youth to reduce the burden of TB/HIV.
PMID- 27487591
TI - DETERMINANTS OF SPECIALTY CHOICE OF RESIDENT DOCTORS; CASE STUDY--AMONG RESIDENT
DOCTORS IN NIGERIA.
AB - OBJECTIVE: This study examined medical specialty selection by Nigerian resident
doctors using a marketing research approach to determine the selection criteria
and the role of perceptions, expected remuneration, and job placement prospects
of various specialties in the selection process. METHODS: Data were from the
Community of residents from April 2014 to July 2014. The cohort included 200
residents, but only 171 had complete information. Data were obtained from a cross
section of resident doctors in the Lagos State University Teaching Hospital and
at the 2014 Ordinary General Meeting of the National Association of Resident
Doctors(NARD) where representatives from over 50 Teaching hospitals in Nigeria
attended. Using a client behaviour model as a framework, a tripartite
questionnaire was designed and administered to residents to deduce information on
their knowledge about and interests in various specialties, their opinions of
sixteen specialties, and the criteria they used in specialty selection. RESULTS:
A total of 171 (85.5%) questionnaires were returned. ln many instances,
consistency between selection criteria and perceptions of a specialty were
accompanied by interest in pursuing the specialty. Job security, job availability
on completion of programme, duration of training and qualifying examinations were
highly correlated with p value < 0.05. Results of the Principal Component
Analysis show two components (with Eigen values greater than one) explaining
65.3% of the total variance. The first component had placement and training and
practice related variables loaded on it while the second component was loaded
with job security and financial remuneration related variables. CONCLUSIONS:
Using marketing research concepts for medical specialty selection (Weissmanet al
2012) stipulates that choice of speciality is influenced by criteria and
perception. This study shows that job security expected financial remuneration,
and examination requirements for qualification are major determinants of the
choice of speciality for residents.
PMID- 27487592
TI - PREVALENCE OF HYPERTENSION AMONG FIREFIGHTERS IN RIVERS STATE, SOUTH-SOUTH,
NIGERIA.
AB - BACKGROUND: High blood pressure is a major cause of morbidity and mortality in
Sub-Saharan Africa and firemen (firefighters) may be especially predisposed to it
or even exacerbate pre-existing hypertension as a result of the nature of their
job. This study was to determine the prevalence of hypertension among firemen in
Rivers state, South-South Nigeria. METHODS: Following ethical clearance, 125
consenting firemen of the Rivers State Fire Service were recruited in this
descriptive cross sectional study. They responded to a pre-tested, structured,
closed-ended self-administered questionnaire which probed their socio
demographics, knowledge, attitude and practice towards hypertension. Also, their
blood pressures heights and weights were measured from where Body Mass Index
(BMI) was calculated. A WalkThrough Survey for immediate work place situation and
safety was carried out. Data collected were later analyzed using descriptive and
analytical statistical tools. RESULTS: There was a 9.6% prevalence of
hypertension among this group of workers in Rivers State. The workforce was
essentially young with a modal age group of between 31-36 years. The attendant
associated risk factors included altered sleep patterns, over weight and smoking
which were all statistically significant P < 0.05. Whilst knowledge of
hypertension was high (96%), the behaviour of respondents towards prevention and
control of hypertension was poor. CONCLUSION: There is hypertension among firemen
of the Rivers State Fire Service occasioned by modifiable risk factors despite
adequate knowledge. It is recommended that intensive health education, early
detection and treatment be instituted among this group of workers.
PMID- 27487593
TI - DEPRESSION, ANXIETY, STRESS, AND THEIR ASSOCIATED FACTORS AMONG CORPS MEMBERS
SERVING IN KEBBI STATE.
AB - BACKGROUND: Depression, anxiety and stress, are not only health problems by
themselves, but also associated with other negative health consequences. The
national youth service is usually characterized by a number of new challenges and
experiences which may require life style adjustments by the corps member.
However, no previous study on psychological factors has been conducted among
corps members. OBJECTIVE: This study was conducted to determine the prevalence of
depression, anxiety and, stress and their associated factors among corps members
serving in Kebbi state. METHODS: A cross-sectional study was conducted among 264
corps members from four local government areas of the state. Selection of the
local government areas and the individual participants was by simple random
sampling. Data was collected from May to June 2014 using a self-administered
questionnaire. Data analysis used chi-square test to identify the relationship
between categorical variables and multivariate logistic regression to identify
the independent factors for depression, anxiety and stress each. RESULTS: The
response rate was 97%. Most of the respondents were males (63.6%), single
(85.5%), and above 20 years of age (71.6%). The overall prevalences of
depression, anxiety and stress among the respondents were 36.4%, 54.5% and 18.2%
respectively. The independent factors for depression were; being from the North
central (OR = 5.99; 95% CI: 2.194-16.354) or South-south; and the perception of
earning enough income (OR = 2.987; 95% CI: 1.062-8.400). For anxiety, male gender
(OR = 0.411; 95% CI: 0.169-0.999); and being from the North central were
significant risk factors (OR = 3.731; 95% CI: 1.450-9.599). Being above 26 years
of age was an independent risk factor for stress (OR = 0.083; 95% CI: 0.018
0.381). Also, those who had ever schooled outside their towns of residence were
less likely to be stressed compared to those who had never (OR = 0.30; 95% CI:
0.110-0.855). All other factors did not show any significant association with any
of the outcome variables in multivariate analysis. CONCLUSION: In conclusion, the
prevalences of depression, anxiety and stress are high among corps members
serving in Kebbi state. There is need to expand the scope of this study to a
national level so as to get a bigger picture of the problem.
PMID- 27487594
TI - PREDICTORS OF INTESTINAL HELMINTHIC INFECTIONS AMONG SCHOOL CHILDREN IN
GWAGWALADA, ABUJA, NIGERIA.
AB - BACKGROUND: Prevalence and risk factors predisposing to intestinal helminthic
infections vary widely. Risk factors to intestinal helminthic infections among
children have not been documented in Gwagwalada, Nigeria which necessitated
present study. OBJECTIVE: To determine risk factors to intestinal helminthiasis
among children aged 1-15 years in Gwagwalada, Nigeria. METHODS: Cross-sectional
study was carried out from June to November, 2011 in public schools using multi
staged, random sampling. Risk factors and helminth species were determined.
Multiple stool samples were analyzed using the Kato-Katz technique. Participants
had a single anal swab to search for Enterobius ova. RESULTS: Of 220 subjects
evaluated, prevalence rate of intestinal helminthic infections was 73.2%. Most
common helminth identified was Ascaris lumbricoides (40.9%) and least was
Trichostrongylus species (2.3%). Logistic regression analysis showed that
significant, predictors of intestinal helminthiasis among subjects were female
gender (P = 0.028), lack of hand washing after defecation (P < 0.01), multiple
sources of drinking water (P = 0.011) and eating of unwashed fruits/vegetables (P
= 0.012). CONCLUSION: The present study identified predictors of intestinal
helminthiasis among children Gwagwalada. Efforts should be made to institute
regular health education, provision of potable water, environmental sanitation
and de-worming programmes for children, as ways of reducing burden of the
infections.
PMID- 27487595
TI - PRIMARY POSTPARTUM HAEMORRHAGE IN FEDERAL MEDICAL CENTRE, OWERRI, NIGERIA: A SIX
YEAR REVIEW.
AB - BACKGROUND: Primary postpartum hemorrhage is an obstetric emergency and is a
leading cause of maternal morbidity and mortality in developing countries. It a
condition that requires vigilance, prompt and appropriate management. OBJECTIVE:
To determine the prevalence and determinants of primary post partum haemorrhage
in Federal Medical Centre Owerri. METHODS: All cases of all cases of primary post
partum haemorrhage managed at FMC Owerri. The case notes were retrieved from the
hospital's Records Department and information on socio-demographic
characteristics, nature of labour (spontaneous, induced or augmented) duration of
labour and mode of delivery and birth weight, estimated blood loss and the need
for blood transfusion were obtained. RESULTS: Out of a total of 4889 deliveries,
3725 (76.2%) women had vaginal delivery while 1,164 (23.8%) women had caesarean
section. Out of these deliveries, 166 women had Primary Post Partum Hemorrhage
(PPH), giving a prevalence of 3.4%. Multiparous women had higher prevalence
compared to nulliparas: 88 (48.3%) versus 37 (22.2%) respectively. The commonest
cause of primary PPH was uterine atony 72 (43.4%) and cervical laceration was the
least cause constituting 13 (7.7%). Caesarean section was associated with higher
prevalence of post partum haemorrhage, 94 (56.4%). Duration of second and third
stages of labour lasting more than 30 minutes and 10 minutes respective were
associated with higher risk of primary PPH:82 (49.5%) and 87 (52.3) respectively.
CONCLUSION: Supervised antenatal care, active management of labour and emergency
obstetric care, if employed religiously will drastically reduce post partum
haemorrhage and thus its associated complications.
PMID- 27487596
TI - PATIENT'S PERCEPTION ON THE QUALITY OF RADIOTHERAPY SERVICES IN TWO TEACHING
HOSPITALS IN NIGERIA.
AB - OBJECTIVE: Patient satisfaction is an important and commonly used indicator for
measuring the quality in health care. Patient satisfaction affects clinical
outcomes, patient retention, and medical malpractice claims. It affects the
timely, efficient, and patient-centered delivery of quality health care. A review
of quality of services from the patient's perspective could be a method of
assessing in order to improve services and achieve total quality management. This
study was designed to assess patients' perception on the quality of Radiotherapy
services in Lagos University Teaching Hospital (LUTH) Lagos and University
College Hospital (UCH) Ibadan. METHODOLOGY: This study is a cross-sectional
study. This research lasted for a period of two months and all patients receiving
radiotherapy within is period were included in this study. A total of 246
questionnaires were completed (152 and 94 in LUTH and UCH respectively) and the
data collection was by semi-structured questionnaire. Data obtained were
collected and analyzed using SPSS statistics [Social Sciences Statistical
Package] 17.0 version. RESULTS: The findings of this research indicated that
68.4% in LUTH and 53.2% in UCH of the patients experienced good care. It also
revealed that there is good interaction between the staff and the patient. Most
of the patients spent more than 3 hours before receiving treatment and also the
reason for such delay were not explained to them. The rate of preferential
treatment was noted to be high. CONCLUSION: This study will contribute positively
towards achieving effective and qualitative radiotherapy services by creating
awareness for the need to minimize patient waiting time as well as the need to
explain the reason for such delays. The department should adopt better ways of
appointment system so that treatment will be on first come first serve basis.
This study will contribute positively towards achieving effective and qualitative
radiotherapy services by creating awareness for the need to minimize patient
waiting time as well as the need to explain the reason for such delays. The
department should adopt better ways of appointment system so that treatment will
be on first come first serve basis.
PMID- 27487597
TI - AWARENESS AND ATTITUDE OF DIABETIC PATIENTS ON DIABETIC EYE COMPLICATIONS IN PORT
HARCOURT, NIGERIA.
AB - BACKGROUND: Diabetes mellitus has significant ocular morbidities leading to
visual impairment and blindness. Most patients are not aware that diabetes
mellitus affect the eye with potential debilitating consequences. The study
examines the awareness and attitude of diabetic patients attending the
endocrinology clinic of the University of Port Harcourt Teaching Hospital, Port
Harcourt, on diabetic eye complications in order to examine factors that may be
contributingto poor visual outcome. AIM: To assess the awareness and attitude of
diabetic patients on diabetic eye complications in Port Harcourt, Nigeria.
METHODS: This hospital-based cross-sectional study carried out between 25th March
and 28th June, 2011 had 225 adult diabetics attending the Endocrinology clinic of
the University of Port Harcourt Teaching Hospital, Port Harcourt daily balloted
for. From questionnaires and ocular examinations were recorded in the data sheets
and analysed using the SPSS version 16 (2007). Simple statistics andcomparisons
of associated variables were made using Chi-square. RESULTS: Of the 225 patients
examined, 128 (56.9%) were aware that diabetes could affect the eye while 97
(43.1%) were not aware. Only a quarter (33, 25.8%) of them knew of specific eye
complications of diabetes.There was no gender specific significant difference (p
= 0.195). Age and educational status significantly affected their awareness (p <
0.005).The duration of diabetes did not have significant impact on the level of
awareness of the patients (p = 0.066). Only 103 (45.8%) of those examined had
ever had previous eye examination of which 26 (26.3%) did so prior to their
diagnosis with diabetes mellitus. Less than a quarter (22.3%) was referred by
doctors for the eye examination. Age, sex, educational status and level of
awareness did not significantly influence the number of those who had the eye
examination while the duration of diabetes significant affect the number of those
who had eye examination (p < 0.005). CONCLUSION: The study underscores the need
to improve patients' education on diabetic eye complications and encourage
primary care physicians to refer diabetic patients for early ocular examination.
PMID- 27487598
TI - HEMATOLOGICAL INDICES IN AUTOMOTIVE TECHNICIANS IN NNEWI, SOUTH-EAST NIGERIA.
AB - BACKGROUND: Occupational exposure to petroleum products is known to be associated
with a number of health risks as well as adverse effects on haematological
indices. OBJECTIVE: To evaluate the effect of exposure to petroleum products on
haematological parameters in automobile mechanics in Nnewi, south-east Nigeria.
SUBJECTS AND METHODS: Fifty (50) automobile technicians and 50 healthy controls
participated in the study. Full blood count was performed for each participant
using the automated Sysmex haemocytometer (Model PCE 210) while data analysis was
done using the SPSS (statistical package for social sciences) version 16 computer
soft ware (Chicago, IL, Inc.). Results were expressed as frequencies, means and
standard deviations; comparison of haematological parameters was made between
subjects and controls and at different durations of exposure using the students'
t-test and analysis of variance (ANOVA), respectively. The level of statistical
significance was p < 0.05 (at 95% CI). Ethical approval was obtained from the
Institutional review board and all participants gave informed consent. RESULTS:
There red blood cell count (RBC) and haematocrit were significantly lower while
the platelet count was significantly higher in test subjects compared with
controls (p values; 0.04, 0.03 and 0.01, respectively). Correspondingly, the mean
cell volume (MCV) and mean cell haemoglobin (MCH) were significantly lower in
test subjects compared with controls (p = 0.62 and 0.03, respectively). The red
cell count, MCV and platelet count significantly decreased with increasing
duration of work exposure (p = 0.001, respectively). CONCLUSION: Occupational
exposure to petroleum products adversely affects blood counts, with a significant
decrease in RBC, MCV and platelet count as duration of exposure increases.
PMID- 27487599
TI - EFFECTS OF ROOT CANAL IRRIGANTS ON THE PLANKTONIC FORM OF ENTEROCOCCUS FAECALIS:
A REVIEW.
AB - BACKGROUND: Bacteria play an essential role in the initiation and perpetuation of
pulpal and periapical pathoses. Enterococcus faecalis is associated with both
primary and persistent endodontic infections. However, the frequency of E.
faecalis in persistent periradicular lesions has been shown to be very higher
than primary infections. AIM: The purpose of this paper was to review the effect
of various irrigation solutions such as sodium hypochlorite, chlorhexidine, MTAD
and Tetraclean against E. faecalis. METHODS: Papers used in this review were
found by searching the key words (Root canal irrigant, sodium hypochlorite,
chlorhexidine, MTAD, Tetraclean, Enterococcus faecalis) in PubMed. RESULTS: It
seems that, although some both sodium hypochlorite and chlorhexidine were very
effective against E. faecalis. The other discussed irrigant and Tetraclean, MTAD,
were effective against E. faecalis in both agar diffusion test and tooth model
experiments. CONCLUSION: It can be concluded that all discussed irrigation
solutions were effective against the planktonic form of Enterococcus faecalis.
PMID- 27487600
TI - GIANT PSEUDOANEURYSM OF A SPLANCHNIC ARTERY; A Case Report.
AB - A true aneurysm is defined as an enlargement of an artery resulting in a diameter
more than 1.5 times the anatomic size. It can be fusiform when it covers the
entire perimeter of the vessel, or saccular when it bulges on one side of the
artery. The pseudoaneurysm is a pulsating encapsulated haematoma in communication
with the lumen of the ruptured vessel,which affects the the intima and the media
and which is stopped from developing by the adventitia and the surrounding
connective tissue. Geographically, aneurysm can be broadly divided into
intracranial and extracranial types.While the neurosurgeon manages the
intracranial types, the vascular surgeon manages the extracranial types. Vascular
surgeons also do divide the extracranial types into central (abdominal-aorto
iliac, thoracic including ascending, transverse aortic arch and descending),
peripheral (extremities) and visceral (splanchnic arteries). Splanchnic artery
aneurysm includes the coeliac, superior mesenteric, inferior mesenteric arteries
including their branches. Of all intra-abdominal aneurysms, only around 5% are
due to the splanchnic arteries,which could be either true or pseudo. The
prevalence has been estimated at 0.1-0.2%.
PMID- 27487601
TI - TRANSMIGRATION OF INTRA-UTERINE DEVICE, EXPLORATORY LAPAROTOMY, RETRIEVAL AND
REPAIR OF PERFORATED UTERUS.
AB - BACKGROUND: Perforation of the uterus following transmigration of Intra-uterine
devise (IUD) is an uncommon finding of insertion of IUD. There is associated
increased risk of accidental pregnancy,morbidity and mortality. AIM: To report a
rare clinical condition in which there was uterine perforation following
migration of IUD and to increase awareness of this condition in our environment.
CASE REPORT: A 37 year old para 6+0 woman (all alive) who presented with a ten
day history of lower abdominal pains following IUD insertion. Examination
revealed tenderness in the suprapubic region and non-visualization of IUD thread
per vaginam. Pelvic USS showed an empty uterine cavity while an abdominopelvic x
ray following tracer IUD insertion showed the IUD to be outside the uterine
cavity. She had an exploratory laparotomy for retrieval of transmigrated IUD and
repair of perforated uterus. CONCLUSION: Transmigrated IUD with uterine
perforation is distressing uncommmon clinical condition, and it is reported with
the hope of increasing the awareness and possibly prevent this avoidable uncommon
complication.
PMID- 27487602
TI - RECURRENT PLEOMORPHIC ADENOMA OF THE UPPER LIP: CASE REPORT AND REVIEW OF THE
LITERATURE.
AB - INTRODUCTION: Pleomorphic adenoma or mixed tumour is a benign salivary gland
tumour, presenting usually in the parotid or submandibular glands. This tumour
contains elements of both epithelial and mesenchymal origin. They are the most
common tumours (50%), (60-65%) of the major and minor salivary glands. The palate
is considered as the most common intraoral site (42.8-68.8%), followed by the
upper lip (10.1%) and cheek (5.5%). CASE REPORT: A 37 year old female Nigerian
house wife was seen with a four year history of painless slowly progressive upper
lip swelling. Prior to her presentation, she had surgery for same swelling in a
peripheral hospital. All other histories were not significant. CONCLUSION: PA
remains the commonest benign minor salivary gland neoplasm and excision with safe
margins the treatment of choice.
PMID- 27487603
TI - REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.
AB - The global scourge of human immunodeficiency virus (HIV) infection is inundating,
especially in sub-Saharan Africa and in particular Nigeria which is home to 10%
of the world's HIV-infected persons. The target of the millennium development
goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in
Nigeria was initially shrouded in denial and apathy. Subsequently, a more
pragmatic approach was launched during the tenure of President Olusegun Obasanjo.
Several policies were formulated. The national prevalence of HIV witnessed some
progressive decline and is currently 4.1%. There is now improvement in both HIV
awareness and counselling and testing. Greater access to antiretroviral therapy
and other support services have also been witnessed with over 300,000 persons
currently on drugs. Notable achievements have been recorded in prevention of
mother to child transmission (PMTC). However, with increased access to
antiretroviral therapy, antiretroviral drug resistance has become inevitable.
Acquired drug resistance is high-82% and transmitted drug resistance ranges
between 0.7 and 4.5%. The achievements were largely facilitated by international
partnerships which have become more streamlined in recent years. A sustained
shift to indigenously sourced financial and manpower resource has become
imperative. It is also important to integrate HIV facilities with other existing
health care facilities for sustainability and cost-effectiveness. In an attempt
to strengthen the national response, President Goodluck Ebele Jonathan launched
the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped
that this well-articulated policy would be well implemented to significantly
reverse the epidemic.
PMID- 27487604
TI - REFERENCE VALUES OF FETAL PEAK SYSTOLIC BLOOD FLOW VELOCITY IN THE MIDDLE
CEREBRAL ARTERY AT 12-41 WEEKS OF GESTATION IN JOS, NORTH CENTRAL NIGERIA.
AB - OBJECTIVES: The objectives of this prospective cross sectional study are (i) to
establish new reference values of peak systolic blood flow velocity measurement
in the fetal middle cerebral artery (MCA-PSV) following validated methodological
guidelines (ii) to correlat peak systolic velocity with gestational age and (iii)
to establish regression prediction model of MCA-PSV for our population. PATIENTS
AND METHODS: Cross-sectional data were obtained from 480 low risk pregnant women
and cross validated by 120 high risk pregnant women between 12 and 41 weeks'
gestation. Reference ranges for MCA-PSV were constructed and for each measurement
linear regression models were fitted separately to the mean and standard
deviations (SD) as a function of gestational age. A comparison was made between
the reference ranges produced in our study and those of Caucasians. RESULTS:
Tables of mean values of peak systolic velocity and percentile with regression
equations of MCA-PSV are resented, with suggested limits of 2.5th as lower
borderline and 97.5th values representing the upper borderline of normal. Foetal
middle cerebral artery peak systolic velocity demonstrated simple continues
increase and strong positive correlation with gestational age. Calculated values
of z were higher than critical values for PSV of subjects and Caucasian values; p
< 0.05 CONCLUSIONS: We have constructed reference ranges for MCA-PSV of gestation
1,241 week period and because the methodological flaws of published study have
been eliminated, cross validated by a control group including larger sample size
drawn from our population we therefore consider this to be useful for clinical
practice.
PMID- 27487605
TI - MATERNAL MORTALITY AUDIT IN A TERTIARY HEALTH INSTITUTION IN NIGERIA: LESSONS
FROM DIRECT CAUSES AND ITS DRIVERS.
AB - INTRODUCTION: Nigeria has the second highest number of maternal deaths in the
world.The study aimed at determining the causes of and non-obstetric contributors
to maternal mortality at a tertiary referral hospital. MATERIALS AND METHODS: It
was a prospective audit of all consecutive maternal deaths in the hospital over a
three-year period. Immediately after the death, information wvas retrieved via a
data collection form. Data were analysed with SPSS-20. RESULTS: Seventy deaths
were examined over the study period. Maternal mortality ratio was 1,265/100,000
live births. The annual ratio decreased steadily over the study period. Most of
the deaths were of multiparous women who had not received any antenatal care, and
were mostly postpartum,within 24 hours of delivery. Most of them were critically
ill on admission to the hospital. Major causes of death were haemorrhage (36%),
sepsis (17%) and hypertensive disorders (16%).Delays were identified in 34.3% of
cases; most (70.1%) were Phase III delays. DISCUSSION: Direct causes of maternal
mortality are consistent with those found in literature. Steps which the centre
has been taken to counter direct and non-obstetric causes are discussed. Possible
strategies to improve health financing and referral system are proffered.
PMID- 27487606
TI - STROKE: CRITICAL APPRAISSAL OF INTENSIVE CARE MANAGEMENT.
AB - BACKGROUND: Stroke is a common medical condition in the medical units. Stroke
patients are usually managed on the medical wards while some that needs organ
support are admitted into the intensive care unit. However there is conflicting
data on the benefits or otherwise of admitting stroke patients into the intensive
care unit. This necessitated this study to know how much benefit is derived from
admitting stroke patients into the intensive care unit. AIM AND OBJECTIVE: The
study aims at the benefits of admitting stroke patients into the intensive care
unit. The objective included studying the prognostic factors that determines the
outcome of stroke patients admitted into the intensive care unit. METHODOLOGY:
The case files of all patients admitted and managed in the intensive care unit of
LAUTECH teaching hospital between 2002 and 2014 were retrieved and were analysed.
The factors used in analyzing included the type of stroke, the age of the
patients, the Glasgow Coma scale at admission, the need for intubation and
mechanical ventilation as well as the percentage mortality in each subsets.
RESULTS: A total of 48 patients were admitted over the study period of which 19
were males and 29 were females. The percentage mortality in females was 78.95
while mortality in males was 62.5%. The higher the age the worse the prognosis,
the higher the GCS the better the prognosis. Patients that were intubated and
ventilated had percentage mortality of 68.8% and better than non ventilated
patients. The hemorrhagic strokes also carries worse prognosis. CONCLUSION: The
admission of stroke patients to the intensive care unit should be individualized
considering the above mentioned prognostic factors. However patients that are
likely to benefit from intensive care unit should be admitted early for them to
derive the maximum benefits.
PMID- 27487607
TI - BODY MASS INDEX IS A POOR PREDICTOR OF MALNUTRITION IN HOSPITALIZED PATIENTS.
AB - OBJECTIVE: Comparison between Subjective Global Assessment and Body Mass Index to
determine the nutritional status in patients admitted in an Internal Medicine
Service. METHODS: Prospective, longitudinal, observational study of a population
of 152 patients, using the Subjective Global Assessment and Body Mass Index.
Plasma levels of albumin, functional capacity weight and income conditions were
determined. Statistics: methods of chi-square test for univariate analysis, non
parametric tests and logistic regression were used. RESULTS: 152 patients, of
which 48.70% had malnutrition, moderate malnutrition 34.2% (group B) and 14.5%
severe malnutrition (group C) were included. No association between Subjective
Global Assessment and Body Mass Index was shown to determine nutritional status.
MalnutrItion was associated with age over 60 years, male sex, and diagnosis of
oncologic andinfectious diseases, as well as the level of functional ability.
CONCLUSIONS: Body Mass Index is not a suitable method to assess the impact of
malnutrition in hospitalized patients compared with the Subjective Global
Assessment.
PMID- 27487608
TI - CHALLENGES IN THE MANAGEMENT OF GLAUCOMA IN A DEVELOPING COUNTRY; A QUALITATIVE
STUDY OF PROVIDERS' PERSPECTIVES.
AB - BACKGROUND: Glaucoma management is challenging to patients as well as to the eye
care providers. The study is aimed at describing the challenges faced by
providers using qualitative methods. METHODS: In-depth interviews were conducted
with selected Ophthalmologists and resident doctors in ophthalmology at centres
offering medical and surgical glaucoma services in Lagos state, Nigeria,
according to established qualitative methods. This was done using semi
structured, open ended questions to explore the providers' perspective on
glaucoma burden, challenges in the management, surgery for glaucoma, acceptance
of glaucoma surgery by patients, and recommendations for improving glaucoma
services. The discussions were recorded with the aid of a micro-cassette
recorder. Familiarisation was done to identify key ideas in the data, then, the
main themes and sub-themes were identified. Quotes that reflect the themes and
sub-themes were then identified in the data. RESULTS: In-depth interviews were
conducted with a total of 11 ophthalmologists and resident doctors in training.
Majority were of the opinion that glaucoma is a significant burden constituting
about 35% of outpatient visits. Identified patient related challenges include;
late presentation, lack of glaucoma awareness, delay in referral from
optometrists, and poor compliance with medications. Shortages in needed equipment
were also identified. Availability, affordability and counterfeiting of drugs
were the major challenges related to medical treatment. Majority of the
participants agreed that surgery should be offered to the patients as soon as the
diagnosis of glaucoma is made. However, continuous monitoring of the patient on
medical treatment is another line of option for them in early cases; if they are
convinced the patients will be compliant. Some respondents considered the current
number of glaucoma surgeries as adequate, while some think otherwise. Reasons put
forward for reluctance to offer glaucoma surgery include; late presentation, lack
of patient satisfaction, complications of surgery, and negative publicity.
CONCLUSION: Even though the challenges in the management of glaucoma in
developing countries are many, they are not insurmountable. There is need for
concerted and integrated efforts involving all cadres of eye care practitioners,
patients, institutions and governments to address this important eye disease.
Improved awareness, provision of adequate equipment, availability and
affordability of medications, need for training and retraining of eye care
providers are all important measures that can lead to better management of the
glaucoma patient.
PMID- 27487609
TI - PREVALENCE OF METABOLIC SYNDROME AMONG APPARENTLY HEALTHY ADULTS IN A RURAL
COMMUNITY, IN NORTH-WESTERN NIGERIA.
AB - BACKGROUND: Metabolic syndrome (MetS) is a cluster of multiple metabolic
abnormalities that increases the risk of cardiovascular morbidity and mortality,
and a resultant severe economic implication. This study assessed the burden of
MetS in a Nigerian rural community setting. METHOD: This was a cross-sectional,
community based study on apparently healthy subjects. A multi stage cluster
sampling technique was employed to recruit the study subjects. A standardized pre
tested questionnaire was used to obtain data, and blood samples from subjects
were analysed using standard laboratory techniques. MetS was defined using the
NCEP-ATP3 criteria. Data were analysed using STATA version II, and a p value of <
0.05 was considered statistically significant. RESULTS: A total of 450 subjects
completed the study, with 38% being males, and a mean age of 40.27 +/- 16.41
years. MetS was found in 116 (25.78%) of the subjects. Of these, systemic
hypertension was found in 91(78.45%), while all (116) had elevated cholesterol
and triglycerides. Abdominal adiposity was found in 45 (38.79%) subjects and 44
(37.93%) had Type 2 diabetes mellitus. CONCLUSION: The prevalence of MetS and its
components in our studied population was high; hence the need for further large
population based studies to determine its predictors in our environment.
PMID- 27487610
TI - PREVALENCE, PATTERN AND RISK FACTORS FOR RETINAL VASCULAR OCCLUSIONS IN A
TERTIARY HOSPITAL IN JOS, NIGERIA.
AB - INTRODUCTION: Retinal vascular occlusions are the second most common retinal
vascular diseases following diabetic retinopathy. They are associated with
several systemic and ocular pathologies and are significant causes of visual
loss. OBJECTIVE: This study aims to determine the prevalence, pattern and risk
factors for retinal vascular occlusions in a tertiary hospital in Jos, Nigeria.
METHODOLOGY: A retrospective review of all cases of retinal vascular occlusions
seen in the eye clinic from January 2011 to December 2014 was carried out. The
patients were identified from the clinic register and their case folders
retrieved. The following data were then extracted from the files; patients' age,
sex, presenting visual acuity, presence of any systemic disorders and type of
retinal vascular occlusion. Data analysis was done using Epi Info 7. RESULTS:
Three thousand eight hundred and twenty one new patients were seen during the
study period and there were 52 (1.36%) cases of retinal vascular occlusions. Only
the case files of 44 (84.6%) patients were available and were analysed. These
were made up of 17 (39%) males and 27 (61%) females. These had a total of 46
retinal vascular occlusions made up of 37 (80.4%) retinal vein occlusions, 8
(17.4%) central retinal artery occlusions and a case (2.2%) of combined central
retinal artery and vein occlusion. Hypertension and diabetes were the most common
systemic risk factors while glaucoma was the most common ocular association.
CONCLUSION: Retinal vascular occlusions are uncommon in our centre but lead to
severe visual loss and are associated with significant systemic pathologies.
PMID- 27487611
TI - CLINICOPATHOLOGICAL PRESENTATION AND MANAGEMENT OUTCOME OF APPENDICITIS IN GOMBE,
NORTH-EAST NIGERIA: A 7-YEAR RETROSPECTIVE AUDIT.
AB - BACKGROUND: Acute appendicitis is a common cause of acute abdomen and right iliac
fossa pain in the study centre with attendant negative appendicectomies. AIM: To
study the demographic pattern, aetiology, clinical presentation and management
outcome of appendicitis. METHODS: This is a retrospective study carried out on
patients, who had appendicectomies between January 2007 and December 2014. A
total of two hundred and thirteen (213) cases were operated during the study
period. Only one hundred and forty one (141) folders retrieved. Relevant clinical
information were entered in to a proforma designed for the study. Statistical
analysis was done using Epi info (version 3.5.1). Quantitative data were
presented in frequencies and percentages,mean and standard deviations were
calculated. RESULT: Out of the 141 patients, 55 (39.0%) were males while 86
(61.0%) were females giving a M:F = 1:1.6. Their ages range from 8 to 65 years.
The peak age group was 21-30 years. Acute inflammation was seen in 69 (48.9%)
patients, lymphoid hyperplasia in 39 (27.7%) patients while parasitic
appendicitis was seen in one (0.7%) patient. Post-operative complications
observed include surgical site infection in 7 (5.0%) patients, delayed wound
healing in 11(7.8%) patients and enterocutaneous fistula in one (0.7%) patient.
CONCLUSION: The diagnosis of appendicitis still rests on the pillars of thorough
clinical evaluation. The judicious use of modern diagnostic equipment will reduce
the rate of negative appendicectomies.
PMID- 27487612
TI - CHALLENGES IN SETTING UP QUALITY CONTROL IN DIAGNOSTIC RADIOLOGY FACILITIES IN
NIGERIA.
AB - BACKGROUND: The Nigerian Nuclear Regulatory Authority (NNRA) was established to
regulate and control the use of radioactive and radiation emitting sources in
Nigeria. Quality control (QC) on diagnostic radiology equipment form part of the
fundamental requirements for the authorization of diagnostic radiology facilities
in the Country. METHOD: Some quality control tests (output, exposure linearity
and reproducibility) were measured on the x-ray machines in the facilities that
took part in the study. Questionnaire was developed to evaluate the frequencies
at which QC tests were conducted in the facilities and the challenges in setting
up QC. RESULTS: Results show great variation in the values of the QC parameters
measured. Inadequate cooperation by facilities management, lack of QC equipment
and insufficient staff form the major challenges in setting up QC in the
facilities under study. The responses on the frequencies at which QC tests should
be conducted did not correspond to the recommended standards; indicating that
personnel were not familiar with QC implementation and may require further
training on QC.
PMID- 27487613
TI - PERCEPTION OF QUALITY CONTROL BY PERSONNEL IN DIAGNOSTIC RADIOLOGY FACILITIES IN
AKWA IBOM STATE, NIGERIA.
AB - BACKGROUND: The perception of quality control (QC) implementation by personnel in
diagnostic radiology facilities can affect service delivery and deprive the
facilities of the benefits associated with QC implementation. The responses by
personnel working in diagnostic radiology facilities in Akwa Ibom State, Nigeria,
concerning the implementation of quality control in diagnostic radiology has been
assessed in order to ascertain their perception of QC implementation. METHOD: A
total of thirty eight (38) radiology personnel from twenty radiology facilities
took part in the study that was conducted using a twenty item questionnaire that
was initially tested for reliability. RESULT: Responses from the surveyed
personnel showed a positive perception for some QC items and a seeming lack of
interest in some other items. This situation may be due to the perceived lack of
interest and lack of cooperation from management of their facilities. The
personnel also felt that they did not have sufficient training to implement QC
and that QC results were difficult to analyse.
PMID- 27487614
TI - TOBACCO ABUSE AND ITS HEALTH EFFECT.
AB - Tobacco smoking is still one of the most important risk factor for Respiratory
and cardiovascular diseases and an estimated 90% of causes of lung cancer are
attributable toTobacco smocking and equally 90% of peripheral vascular disease in
non-diabetic population is attributable to Tobacco smoking, despite the health
effect there is disturbing figures of people who take up smoking habit daily and
increase level of failed quit smoking attempts. Environment and genetics still
plays major role, and various forms of tobacco is used worldwide and its health
consequence has been highlighted. Monitoring tobacco use and prevention policies
through effective tax laws is paramount to reduction of the tobacco health
effects in our environments.
PMID- 27487615
TI - CURRENT MANAGEMENT OF PERIPARTUM CARDIOMYOPATHY: A REVIEW.
AB - BACKGROUND: Demarkis et al in 1971 described 27 patients who presented during
pueperium with cardiomegaly, abnormal electrocardiographic findings, congestive
heart failure and named the syndrome "peripartum cardiomyopathy". The aim of this
review is to document the current concepts in the management of peripartum
cardiomyopathy. MATERIALSAND METHODS: A search of the literature was done using
PubMed, Goggle scholar and books from authors' collections. RESULTS: The cause of
the disease might be environmental and genetic factors. Diagnostic
echocardiographic criteria include left ventricular ejection fraction of less
than 45% or a combination of M-mode fractional shortening of less than 30% and
end diastolic dimension of greater than 2.7 cm/m2. Electrocardiogram, magnetic
resonance imaging, endomyocardial biopsy and cardiac catheterization aid in the
diagnosis and management of peripartum cardiomyopathy. Treatment includes both
conventional pharcomological heart failure and peripartum cardiomyopathy targeted
therapies.Therapeutic decisions are influenced by drug safety profiles during
pregnancy and lactation. Mechanical support and transplantation might be
necessary in severe cases. CONCLUSION: Peripartum cardiomyopathy is an uncommon
but life threatening cardiac failure of unknown aetiology encountered in late
pregnancy or postpartum period. Management aims at improving heart failure
symptoms through conventional therapies and then at administering targeted
therapies.The risk of recurrence in future pregnancies should always be
considered.
PMID- 27487616
TI - DISTAL ILEAL STENOSING SUBSEROSAL LIPOMA: A CASE REPORT.
AB - Lipoma is the commonest soft tissue tumour and ubiquitous in distribution. The
gastrointestinal tract is a rare site for this neoplasm. This 38 years old
patient presented to the surgical emergency unit of the Jos University Teaching
Hospital with features of intestinal obstruction which was confirmed by plain
abdominal X-ray. Patient was resuscitated and had exploratory laparotomy. At
surgery, a dilated, oedematous, and pale segment of ileum was seen measuring 56
cm in length and 10 cm short of the ileo-caecal junction, where an obstruction
had occurred.The distal segment was collapsed. A limited right hemi-colectomy was
done with ileocolic anastomosis. Specimen received atthe Histopathology
Laboratory consisted of 45 cm of the ileum, the caecum, appendix, and proximal 25
cm of the colon in continuity. There was stenosis affecting the distal 30 cm of
the ileum. The wall of the stenosed part of ileum had intramural fat at the sub
serosal locale. Histology confirmed the presence of sheets of matured adipocytes
between the muscularispropria and serosa. Patient condition improved and was
discharged seven days after surgery. This case is reported five months after
surgery. We recommend that lipoma be at all times considered in the differential
diagnosis of intestinal obstruction.
PMID- 27487617
TI - TMJ ANKYLOSIS: MANAGEMENT WITH RECONSTRUCTION AND INTERPOSITIONAL ARTHROPLASTY.
AB - Temporomandibular joint (TMJ) ankylosis is a very desolating structural condition
that involves fusion of the mandibular condyle to the base of the skull. It
causes difficulty in mastication and breathing. Trauma and Infections are usually
responsible. If trauma occurs in young age, it leads to disturbance in growth &
facial asymmetry. Treatment of temporomandibular joint (TMJ) ankylosis usually
requires adequate excision of the involved ankylotic block (arthroplasty) or
interpositional arthroplasty using autogenous or alloplastic materials. Early
mobilization, physiotherapy & strict follow up are essential to prevent postop
adhesions. In our cases fascia lata was used as an interpositional grafting
material. One case was treated by gap arthroplasty, second case by costochondral
graft & third case was managed with titanium condylar prosthesis.
PMID- 27487618
TI - FOREIGN BODY IN THE NASOPHARYNX; MASQUERADING AS PHARYNGOTONSILLITIS.
AB - Foreign body (FB) in the aerodigestive tracts has been commonly reported but
findings of impacted foreign bodies in the nasopharynx following
inhalation/ingestion are very rare. Most of the FB gets lodged as a result of
forceful vomiting, coughing,and digital manoeuvres for removal of FB in the
oropharynx. Several objects have been identified lodged in the nasopharynx. No
age group is spared although most victims are children under 10 years of age.
Foreign bodies in the nasopharynx can be uneventful or potentially dangerous
depending on type, size and location as it may cause sudden airway obstruction,
or local pressure necrosis of alimentary or respiratory tract or both.
Presentation in children is usually with a history of swallowed FB which may not
be witnessed in children, choking, cough, bluish discolouration, breathlessness,
drooling of saliva, halitosis, rhinorrhoea, snoring, stridor, dysphagia, vomiting
and dysphonia. A foreign body in the nasopharynx is a challenge to patient,
parents, the physician and the ENT surgeon, as it may be miss-diagnosed, in the
index case, as Pharyngotonsilitis. The index patient, a 14 month child,was
presented with a two days history of fever, drooling of saliva, mouth breathing,
and digital manipulation. Lateral imaging of the post nasal space following
initial treatment with antibiotics, aided the diagnosis of a periwinkle shell in
the nasopharyngx that was removed during a nasopharyngoscopy under general
anaesthesia without complication and subsequently discharged home. This
emphasizes a high index of suspicion for FB in the nasopharynx in children with
history of missing foreign body, digital manipulation, drooling of saliva and
mouth breathing. Lateral X-ray of the postnasal space, neck, chest and abdomen
should be the minimum investigation required.
PMID- 27487619
TI - [Not Available].
PMID- 27487620
TI - [Curative treatment for esophageal cancer: results of a multidisciplinary
consensus].
AB - The management of patients with resectable cancer of the esophagus or
gastroesophageal junction is currently not standardized. A multi- disciplinary
regional consensus has been developed and is presented in this article. The
standard workup includes an upper endoscopy, ultrasonography and a CT-scan. For
locally advanced tumors, surgery should be associated with either preoperative
radiochemotherapy orperioperative chemotherapy after discussion in
multidisciplinary tumor board. Before the operation, smoking and alcohol
cessation is imperative and nutritional status should be optimized. Nowadays,
surgery is well standardized and generally performed minimally invasive accesses.
After surgery, clinical and oncological follow-up is necessary.
PMID- 27487621
TI - [Giant hernias with loss of domain: what is the best way to prepare patients?].
AB - Giant hernias with loss of domain induce physiological modifications that impair
quality of life and make more complex their surgical management. A good
preparation of patients before surgery is the key to an eventless postoperative
course. The progressive pre-operative pneumoperitoneum (PPP) is one of the
described abdominal augmentation protocols which can help patients to tolerate
hernia content reintegration and avoid components separation technique during
hernia repair. This article describes the management of these complex patients.
We also report the case of a patient who follows successfully a PPP protocol.
PMID- 27487622
TI - [Cystic lesions of the pancreas from the general practitioner's point of view].
AB - The detection rate of cystic lesions of the pancreas has increased following the
widespread use of high-resolution imaging technologies. CT-scan, MRI and echo
endoscopy are diagnostic modalities. Pseudocyst is the most common lesion. It is
benign and can be managed with endoscopic treatment. Mucinous cystic neoplasia
and Intraductal Papillary Mucinous Neoplasia (IPMN) carry a risk for malignant
transformation. The surgical treatment of these lesions has to be discussed by a
multidisciplinary board. Serous cystic neoplasia and pseudopapillar and solid
neoplasia are two rare types of lesion. The aim of this article is to present the
diagnostic pathway and the management of these lesions from the general
practitioner point of view.
PMID- 27487623
TI - [Preoperative assessment for extended hepatic resection].
AB - The number of major hepatectomy performed for the treatment of primary or
secondary liver cancer has increased over the past two decades. By definition, a
major hepatectomy includes the resection of at least three liversegments.
Advances in anesthesiology, surgical and radiological techniques and
perioperative management allowed a broad patient selection with increased
security. Every case must be discussed in multidisciplinary tumor board, and
preoperative assessment should include biological, volumetric and functional
hepatic parameters. In case of preoperative insufficient liver volume, portal
vein embolization allows increasing the size of liver remnant. This paper aims
describing preoperative work-up.
PMID- 27487624
TI - [Multidisciplinary treatment of locally advanced rectal cancer].
AB - Treatment of patients with locally advanced rectal cancer remains challenging.
Preoperative imaging with pelvic MRI allows to identify patients for multimodal
treatment including induction chemothe- rapy or neoadjuvant radio-chemotherapy
and an extended surgical resection. With multidisciplinary approach and an
experienced team, excellent oncologic results may be achieved, as well as a good
function and quality of life, even with preservation of the anus in the majority
of patients.
PMID- 27487625
TI - [Management of peritoneal carcinomatosis with cytoreductive surgery and
hyperthermic intraperitoneal chemotherapy].
AB - In 2016, peritoneal carcinomatosis can be considered as a chronic disease that
can be treated and sometimes cured. Hyperthermic Intra PEritoneal Chemotherapy
(HIPEC) is a procedure developed in the eighties. Combined with CytoReductive
(CR) surgery, this protocol underwent a considerable expansion in Washington
Cancer Institute. CR combined with HIPEC was demonstrated to be the only curative
treatment for PseudoMyxoma Peritonei syndrome (PMP). It is actually approved in
the management of peritoneal carcinomatosis of ovarian, colorectal, or peritoneal
primitive (mesothelioma) origin but is still studied for gastric cancer. CR/HIPEC
is associated with an important mortality and morbidity. This article takes stock
of indications to CR/HIPEC.
PMID- 27487626
TI - [Not Available].
PMID- 27487627
TI - [Not Available].
PMID- 27487628
TI - [Not Available].
PMID- 27487629
TI - [Not Available].
PMID- 27487630
TI - [Not Available].
PMID- 27487631
TI - [Not Available].
PMID- 27487632
TI - [Not Available].
PMID- 27487634
TI - [Not Available].
PMID- 27487633
TI - [Not Available].
PMID- 27487635
TI - NEOSTIGMINE VERSUS SUGAMMADEX FOR REVERSAL OF NEUROMUSCULAR BLOCK.
PMID- 27487636
TI - REMIFENTANIL VS FENTANYL DURING DAY CASE DENTAL SURGERY IN PEOPLE WITH SPECIAL
NEEDS: A COMPARATIVE, PILOT STUDY OF THEIR EFFECT ON STRESS RESPONSE AND
POSTOPERATIVE PAIN.
AB - BACKGROUND: People with special needs undergoing dental surgery frequently
require general anesthesia. We investigated the effect of remifentanil vs
fentanyl on stress response and postoperative pain in people with special needs
undergoing day-case dental surgery. METHODS: Forty-six adult patients with
cognitive impairment undergoing day-case dental surgery under general anesthesia
were allocated to receive intraoperatively either fentanyl 50 MUg iv bolus (group
F, n = 23) or continuous infusion of remifentanil 0.5-1 MUg/kg/min (group R, n =
23). Iintraoperative hemodynamic parameters were recorded and serum inflammatory
mediators [tumor necrosis factor-alpha, substance-P], stress hormons (melatonin,
cortisol) and beta-endorphin were measured. Postoperative pain was assessed
during the first postoperative 12 hours with the Wong-Baker faces pain-rating
scale. RESULTS: Demographics were similar in two groups. The two groups did not
differ regarding their effects on inflammatory mediators, stress hormons and
postoperative pain scores. However, the use of remifentanil prevented
intraoperative increases of arterial blood pressure and heart rate. CONCLUSIONS:
Remifentanil and fentanyl did not affect differently stress and inflammatory
hormones during day-case dental surgery, although remifentanil may render
intraoperative management of hemodynamic responses easier. Both opioids are
equally efficient for postoperative pain management following dental surgery in
people with special needs.
PMID- 27487637
TI - COMPARISON OF THE BONFILS INTUBATION FIBRESCOPE VERSUS C-MAC VIDEOLARYNGOSCOPE.
AB - BACKGROUND: This prospective, randomized, single blind, single operator study was
conducted to compare hemodynamic responses when endotracheal intubation was
performed using the Bonfils intubation fibrescope versus the C-MAC
videolaryngoscope. METHOD: Forty-four ASA I patients aged between 18 and 60
years, scheduled for elective surgery requiring endotracheal intubation were
recruited. They were randomized into the Bonfils group or C-MAC group.
Hemodynamic changes, laryngeal view, duration of intubation and post intubation
complications were evaluated. Mean arterial pressure, heart rate and oxygen
saturation were monitored pre and post-induction, pre and post-intubation, and at
1 minute intervals thereafter for 10 minutes. RESULTS: Endotracheal intubation
was successful at first attempt in 90.9% in both groups. Heart rate was
significantly higher in the Bonfils group (p < 0.05) compared to the C-MAC group
and values were sustained throughout the study. There was no difference in the
mean arterial pressure (MAP) between the two groups. Mean time to intubation was
significantly longer in the Bonfils group (28.8 vs. 24.7 seconds, p = 0.02).
There were no significant differences in laryngeal view and post intubation
complications between the groups. CONCLUSION: Intubation using the Bonfils
intubation fibrescope took longer, and resulted in significantly higher heart
rate when compared with the C-MAC videolaryngoscope.
PMID- 27487638
TI - A COMPARATIVE STUDY OF THE ANALGESIC EFFECT OF INTRAVENOUS PETHIDINE VS.
KETOROLAC AFTER INGUINAL HERNIA SURGERY IN CHILDREN UNDER GENERAL ANESTHESIA.
AB - INTRODUCTION: Postoperative pain due to tissue damage caused during surgery not
only causes discomfort for the patients, but can also result in prolonged
hospitalization, increased morbidity and respiratory disorders, and readmission
to the hospital. For postoperative pain control, numerous methods and medications
have been suggested, such as non-steroidal anti-inflammatory drugs (NSAIDs) and
narcotics. Pethidine, as a narcotic analgesic, and ketorolac, as an NSAID, are
widely used for pain control. Thus, in this study, the effects of these two drugs
were studied and compared in terms of pain control after inguinal hernia surgery
in children of 1-12 years of age. MATERIALS AND METHODS: Sixty-six children
undergoing inguinal herniorrhaphy were selected and randomly divided into 2
groups. The first group received 0.5 mg/kg ketorolac and the second group
received 1 mg/kg pethidine during extubation. Postoperative pain (using Wong
Baker pain scale) and complications were measured until 24 hours after surgery.
RESULTS: Mean and standard deviations of postoperative pain 1 hour after surgery
in the pethidin and ketorolac groups were 5.06 +/- 1.41 and 3.88 +/- 0.93,
respectively. The scale was significantly lower in the ketorolac group (P <
0.001). Postoperative pain intensity 2 hours after surgery in these two groups
was 4.48 +/- 1.52 and 3.55 +/- 1.15, respectively, and the difference between the
two groups was significant (P = 0.006). The variation in postoperative pain
intensity in the ketorolac group was statistically lower than the pethidin group
(P = 0.020). CONCLUSION.
PMID- 27487639
TI - SHORT-TERM POSTOPERATIVE COGNITIVE FUNCTION OF ELDERLY PATIENTS UNDERGOING FIRST
VERSUS REPEATED EXPOSURE TO GENERAL ANESTHESIA.
AB - BACKGROUND: General anesthesia (GA) may affect cognitive functions and result in
postoperative cognitive dysfunction. The aim of our prospective pilot study was
to compare the short-term postoperative cognitive function of unimpaired elderly
patients undergoing first versus repeated exposure to GA. METHODS: After approval
from the Hospital Ethics Committee and informed consent of all participants, 46
patients, 70.1 +/- 7.1 years of age, 20 men and 26 women were enrolled in the
study. Twenty-five patients belonged to group A (never received GA before) and 21
patients belonged to group B (received at least once GA the last 5 years). Each
patient was evaluated preoperatively and the 8th day postoperatively by a blinded
examiner with a battery of neurocognitive tests. RESULTS: Group B patients
performed preoperatively worse in Trail Making Test Part A, Stroop Color and Word
Test and Three Words-Three Shapes Test. Postoperatively there were differences in
almost every neurocognitive test, with group B patients again achieving the worse
scores. This came along with increased Beck Depression Inventory Test score and
increased incidence of delirium in Group B patients. CONCLUSION: Our pilot study
suggests that prior exposure of elderly patients to GA might lead to prolonged
cognitive impairment and repeated GA exposure seems to be a potential risk factor
for greater short-term postoperative cognitive impairment.
PMID- 27487640
TI - COMPARISON OF THE EFFECTS OF PREEMPTIVE INTRAVENOUS AND RECTAL ACETAMINOPHEN ON
PAIN MANAGEMENT AFTER INGUINAL HERNIORRHAPHY IN CHILDREN: A PLACEBO-CONTROLLED
STUDY.
AB - BACKGROUND: Postoperative pain management is a critical concern in pediatric
surgery. Acetaminophen is the safest and most widely used analgesic in children.
The present study compared the analgesic efficacy of intravenous (IV) and rectal
acetaminophen versus placebo in children undergoing inguinal herniorrhaphy.
METHODS: A total of 120 children, who were candidate for elective surgical repair
of unilateral inguinal hernia, were enrolled and randomly allocated to four
groups of 30 patients each to receive IV acetaminophen, acetaminophen
suppository, IV placebo, and placebo suppository during surgery. Postoperative
pain scores, measured on the Face, Legs, Activity, Cry, and Consolability (FLACC)
scale, were recorded and compared. RESULTS: The four groups had no significant
differences in the mean age, weight, length of stay in the recovery room, and
duration of operation. The frequency of postoperative vomiting was significantly
lower in the IV and rectal acetaminophen groups compared to the two placebo
groups (P = 0.04). The mean pain scores of the two acetaminophen groups were
similar during the first two hours after surgery. These scores were significantly
lower than the scores of the placebo groups. However, the four groups were not
significantly different in terms of pain scores at the fourth, sixth, and 12th
postoperative hours. During the first hour after surgery, IV acetaminophen had
the largest analgesic effect. Moreover, among all four groups, the IV
acetaminophen group had the highest sedation level in the recovery room.
CONCLUSION: Both IV and rectal acetaminophen were more effective than placebo in
pain relief after inguinal hernia repair in children. They were also associated
with lower frequencies of postoperative vomiting. The greatest analgesic efficacy
of both forms was observed during the first two hours after surgery.
PMID- 27487641
TI - ANESTHETIC MANAGEMENT DURING COMBINED LIVER AND KIDNEY TRANSPLANTATION.
AB - Combined liver and kidney transplantation is a highly demanding and challenging
procedure for anesthesiologists due to the lengthy and complicated nature of the
procedure, the critical patient condition and the need to balance the
intravascular volume to maintain the venous outflow of the hepatic allograft and
also the diuresis of the renal allograft. Intravascular volume management and
coagulation control, seem to be the most important issues during combined liver
and kidney transplantation. There is sparsity of data in the literature
concerning the anesthetic and fluid management in CLKT. We present and discuss
the anesthetic management in a case series in three patients, who underwent
combined liver and kidney transplantation in our institution during the last two
years.
PMID- 27487642
TI - TORSADES DE POINTES ASSOCIATED WITH TAKOTSUBO CARDIOMYOPATHY IN AN ANOREXIA
NERVOSA PATIENT DURING EMERGENCE FROM GENERAL ANESTHESIA.
AB - Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a
disease in which the patient exhibits transient, reversible left ventricular
dysfunction that is triggered by physical or emotional stress. Prolongation of QT
interval, a risk factor for arrhythmia and sudden death, has been reported to be
prevalent among patients with Takotsubo cardiomyopathy and is also observed in
those with severe anorexia nervosa. In this report, we describe the rare case of
a 30-year-old female patient with anorexia nervosa who developed Torsades de
Pointes associated with Takotsubo cardiomyopathy during emergence from general
anesthesia for emergency exploratory laparotomy.
PMID- 27487643
TI - PERIOPERATIVE CARE OF A CHILD WITH CRISPONI SYNDROME.
AB - Crisponi syndrome is an autosomal recessive disorder characterized by
intermittent episodes of muscular contraction of the facial muscles with trismus
and excessive salivation simulating a tetanic spasm. These episodes occur in
response to tactile stimulation or during crying. Associated physical and
constitutional findings include characteristic facial anomalies, camptodactyly,
intermittent hyperthermia, and feeding difficulties. We present a 15-month-old
girl who required anesthetic care during laparoscopic fundoplication and gastric
tube insertion. The perioperative implications of the disorder are reviewed and
suggestions for anesthetic management provided.
PMID- 27487644
TI - LOEYS-DIETZ SYNDROME: PERIOPERATIVE ANESTHESIA CONSIDERATIONS.
AB - Loeys-Dietz syndrome (LDS) is a rare autosomal dominant disease related to
genetic mutations in receptors for the cytokine transforming growth factor
receptor type 1 (TGFB-R1) or 2 gene (TGFB-R2) on the cell surface. LDS results in
abnormal protein synthesis and dysfunctional connective tissue, which can result
in unique cardiovascular anesthesia challenges related to perioperative
management. Patients with LDS may manifest hypertelorism, bifid uvula or cleft
palate, and arterial tortuosity. Virtually all LDS patients show some type of
abnormal skin findings and bleeding tendency. These patients may show a rapid
progression of aortic dilation, regurgitation, and a propensity towards rupture
and/or dissection at a much earlier age and smaller aneurysm size. LDS patients
who require surgical intervention require meticulous vigilance from the
anesthesiologist. We describe a 26 year old patient with documented LDS type 1
who presented for repair of an ascending/root aneurysm in this case report.
Recognition of LDS and intra-operative management of the cardiovascular
manifestations of this disease is paramount in ensuring successful surgical
outcome and to limit morbidity and mortality.
PMID- 27487645
TI - ECG-ELECTRODE INDUCED HYPOPIGMENTATION.
AB - Skin reactions following the application of electrocardiography (ECG) electrodes
have been reported in adults and children, and are postulated to result from
contact with the conductive gel or adhesive used on the electrodes. Although
contact dermatitis is the usual cause of such reactions, contact depigmentation
or hypopigmentation may also occur. We report a case of hypopigmentation in a
healthy boy following continuous electrocardiography monitoring during general
anesthesia for dental rehabilitation.
PMID- 27487646
TI - PERIOPERATIVE CARE OF AN INFANT WITH GOMEZ-LOPEZ-HERNANDEZ SYNDROME.
AB - Gomez-Lopez-Hernandez syndrome, also known as cerebello-trigeminal dermal
dysplasia, is a rare neurocutaneous syndrome classically characterized by the
triad of rhombencephalosynapsis, trigeminal anesthesia, and bilateral parietal
alopecia. Associated clinical features include a characteristic facial appearance
(mid-face hypoplasia, hypertelorism, and low-set, posteriorly rotated ears),
brachycephaly, strabismus, ataxia, developmental delay, short stature, and
corneal opacities. Given the associated congenital anomalies, anesthetic care may
be required for various surgical interventions. We report a 7-month-old with
Gomez-Lopez-Hernandez syndrome scheduled for laparoscopic gastrostomy with tube
placement and frenulotomy under general anesthesia. The potential perioperative
implications of such patients are reviewed and options for anesthetic care
discussed.
PMID- 27487648
TI - ARTERIAL CANNULATION: SIMPLE SWAYING MANEUVER MAY BE AN ANSWER TO COUNTER
FAILURE/COMPLICATION RATES.
PMID- 27487647
TI - ANESTHESIA FOR CHARCOT-MARIE-TOOTH DISEASE: CASE REPORT.
AB - Charcot-Marie-Tooth disease comprises a group of disorders characterized by
progressive muscle weakness and wasting. Reviewing the anaesthetic literature
produced conflicting reports about the best anaesthetic options for patients with
CMTD; as they are at increased risk of prolonged response to muscle relaxants,
malignant hyperthermia and risks of regional anaesthesia. We present a case of
the successful use of total intravenous anaesthesia with dexmedetomidine and
propofol combined with caudal block using bupivacaine mixed with dexmedetomidine
without any complications, for a 17 year old male patient with Charcot Marie
Tooth disease who underwent a lower limb orthopedic surgery.
PMID- 27487649
TI - PALPATE INTERCRISTAL LINE CORRECTLY: NOT TRANSGRESS TOO HIGH: CAN BE TOO CLOSE TO
CONUS MEDULLARIS.
PMID- 27487650
TI - Editorial.
PMID- 27487651
TI - Treatment of Bignathic Malocclusions With Multistage Active Force Orthodontic
Movements in a Cat.
AB - Abstract Untreated malocclusions may lead to negative oral health sequelae
including, but not limited to, pain, dental trauma, periodontal disease, and
endodontic disease. Thus, orthodontic treatments of malocclusion in companion
animals are often pursued for reasons other than cosmesis. Treatment may provide
a pain-free, functional occlusion with the opportunity for the best possible long
term oral health. This report describes the multistage orthodontic treatment of a
bignathic malocclusion in a cat, highlighting the complexities and complications
that may arise with orthodontic movement of multiple teeth.
PMID- 27487652
TI - Bridging Plate Development for Treatment of Segmental Bone Defects of the Canine
Mandible: Mechanical Tests and Finite Element Method.
AB - With regard to the canine mandible, a mistaken concept of application is to
assume that systemic plate-bone resistance is provided by the implant so that
biomechanical position could be ignored. Because the alveolar border of the
mandible is a tensile zone, the plate would ideally be positioned near this area
while avoiding important structures. The aim of this study was to develop 2
bridging plates for the treatment of a segmental bone defect of the canine
mandible using monocortical screws to avoid damage to the tooth roots and
remaining neurovascular structures. Computed tomography images of the heads of 4
dogs (rottweiler, Doberman, boxer, and miniature poodle breeds) were used as
models to develop the project. The images were reconstructed in 3-dimensional
(3D) format. For each dog breed, 6 mandible prototypes were produced, each with a
segmental bone defect in the right mandible. The mandibular reconstruction was
performed with pure titanium bridging plate and locking screws. One plate model
was developed for medium- and large-breed dogs and another for small-breed dogs.
Mechanical testing showed the platemandible system resists the bite forces in all
dog breeds. All safety factors were greater than I in the platemandible system
for medium- and large-breed dogs and greater than 10 in the plate-mandible system
for small-breed dogs. Thus, bridging plates designed with differentiated geometry
and monocortical locking screws showed mechanical resistance to support simulated
induced bone model defects and were able to support at least 5 times the value of
bite force for each evaluated dog.
PMID- 27487653
TI - Quantification of Canine Dental Plaque Using Quantitative Light-Induced
Fluorescence.
AB - The aim of this work was to evaluate Quantitative Light-induced Fluorescence
(QLF) as an alternative to the established Logan and Boyce method for determining
plaque coverage of dogs' teeth. In a series of studies in conscious and
anesthetized dogs, QLF showed good intra-photographer repeatability (coefficient
of variation [CV] of 7.5% for undisclosed teeth) and inter-photographer
reproducibility (CV of 3.2% for undisclosed teeth and 8.5% for disclosed teeth).
The QLF software accurately identifies areas of plaque as demonstrated by
comparison to the variability of 5 human scorers, manually marking plaque on QLF
acquired images (P = 0.1). There was good agreement with the modified Logan and
Boyce method in the percentage reduction in plaque accumulation measured when
dogs were fed an oral care chew versus no chew. To see a 15% difference in plaque
accumulation, which is considered sufficient by the Veterinary Oral Health
Council to differentiate between 2 treatments, a retrospective power analysis
(90%) of the data established that only 7 dogs would be required, compared to 19
dogs for the modified Logan and Boyce method. QLF is a reliable method for
measuring dental plaque in dogs with the added advantage that it is not
subjective and requires fewer animals.
PMID- 27487654
TI - Measuring Rabbit (Oryctolagus cuniculus) Tooth Growth and Eruption by
Fluorescence Markers and Bur Marks.
AB - Rabbits (Oryctolagus cuniculus) and rodents possess continuously growing teeth,
and dental problems are a major health issue in these species. Knowledge of tooth
growth characteristics is required to adequately treat dental problems and advise
owners concerning diets. Most research was performed using bur marks and
measuring eruption and wear manually. However, this method cannot be applied to
teeth less rostral than the first premolar; therefore, for evaluation of molars,
other methods are needed. We evaluated the use of fluorochromes xylenol orange
and calcein green to measure growth rates of rabbit teeth and compared this
method to results obtained by manually measuring the distance between a bur mark
and the gingival margin of the same tooth (eruption) and by measuring the
distance between the bur mark and the apex of the same tooth on computed
tomography scans (growth). Apical fluorochrome measurements correlated well with
eruption and growth rates obtained with bur marks, whereas measurements coronal
to the pulp cavity did not. Growth rates were approximately 1.9 mm/wk for
maxillary and 2.2 mm/wk for mandibular incisors. Growth rates of premolars were
2.14 +/- 0.28 mm/wk in rabbits on a grass/rice hulls/sand pelleted diet and 0.93
+/- 0.18 mm/wk in rabbits on a hay diet. Growth of molars could only be assessed
using the measurement in dentin on the wall of the pulp cavity, which does not
account for the real growth. However, being similar to this measurement in
premolars, one could hypothesize similar growth in molars as in premolars. We
conclude that the application of fluorochrome staining can be used to measure
tooth growth in teeth that are not accessible for bur marks or in animals that
are too small to assess tooth eruption or growth by bur marks.
PMID- 27487655
TI - Modified Labial Button Technique for Maintaining Occlusion After Caudal
Mandibular Fracture/Temporomandibular Joint Luxation in the Cat.
AB - Maxillofacial trauma in cats often results in mandibular symphyseal separation in
addition to injuries of the caudal mandible and/or temporomandibular joint (TMJ).
Caudal mandibular and TMJ injuries are difficult to access and stabilize using
direct fixation techniques, thus indirect fixation is commonly employed. The
immediate goals of fixation include stabilization for return to normal occlusion
and function with the long-term objective of bony union. Indirect fixation
techniques commonly used for stabilization of caudal mandibular and
temporomandibular joint fracture/luxation include maxillomandibular fixation
(MMF) with acrylic composite, interarcade wiring, tape muzzles, and the bignathic
encircling and retaining device (BEARD) technique. This article introduces a
modification of the previously described "labial reverse suture through buttons"
technique used by Koestlin et al and the "labial locking with buttons" technique
by Rocha et al. In cases with minimally displaced subcondylar and pericondylar
fractures without joint involvement, the labial button technique can provide
sufficient stabilization for healing. Advantages of the modified labial button
technique include ease of application, noninvasive nature, and use of readily
available materials. The construct can remain in place for a variable of amount
of time, depending on its intended purpose. It serves as an alternative to the
tape muzzle, which is rarely tolerated by cats. This technique can be easily used
in conjunction with other maxillomandibular repairs, such as cerclage wire
fixation of mandibular symphyseal separation. The purpose of this article is to
demonstrate a modified labial button technique for maintaining occlusion of
feline caudal mandibular fractures/TMJ luxations in a step-by-step fashion.
PMID- 27487656
TI - [CHARACTERISTICS OF OSTEOCYTE CELL LINES FROM BONES FORMED AS A RESULT OF
MEMBRANOUS (SKULL BONES) AND CHONDRAL (LONG BONES) OSSIFICATION].
AB - The aim of this work was to analyze the literature data and the results of
authors' own research, to answer the question--if the osteocytes of bone tissues
resulting from membranous and chondral ossification, belong to one or to
different cell lines. The differences between the cells of osteocyte lines
derived from bones resulting from membranous and chondral ossification were
established in: 1) the magnitude of the mechanical signal, initiating the
development of the process of mechanotransduction; 2) the nature of the
relationship between the magnitude of the mechanical signal that initiates the
reorganization of the architecture of bone structures and the resource of their
strength; in membranous bones significantly lower mechanical signal caused a
substantially greater increment of bone strength resource; 3) the biological
activity of bone structures, bone fragments formed from membranous tissue were
more optimal for transplantation; 4) the characteristics of expression of
functional markers of bone cells at different stages of their differentiation; 5)
the nature of the reaction of bone cells to mechanical stress; 6) the sensitivity
of bone cells to one of the factors controlling the process of
mechanotransduction (PGI2); 7) the functioning of osteocytes during lactation.
These differences reflect the functional requirements to the bones of the
skeleton--the supporting function in the bones of the limbs and the shaping and
protection in the bones of the cranial vault. These data suggest that the results
of research conducted on the bones of the skull, should not be transferred to the
entire skeleton as a whole.
PMID- 27487657
TI - [THE DISTRIBUTION OF CORTICO-THALAMIC PROJECTIONS OF DIFFERENT OF DIFFERENT
SOMATOTOPIC REPRESENTATIONS OF PRIMARY MOTOR AND SENSORY CORTEX].
AB - The peculiarities of localization and distribution of cortico-thalamic efferents
of different somatotopical representations of primary motor (MI) and sensory (SI)
cortex were studied in cat brain. MI efferent fibers (4y, 6ab areas)
preferentially projected to ventral posterolateral and medial (VPL, VPM),
ventrolateral (VL), and reticular (R) nuclei, localized in rostral part of the
thalamus (T), as opposed to SI (areas 1, 2, 3a, 3b), which projected
preferentially to caudal part of T, VPL, VPM and R nuclei. Latero-medial
organization of cortico-thalamic connections was demonstrated, with predominant
localization of cortical representation of hindlimbs in the lateral part of VPL,
of forelimbs--in the medial part of VPL, of face and head--also in VM and VPM.
Quantitative analysis of the distribution of corticothalamic efferents of
different somatotopical representations of MI has demonstrated the most
extensive, massive connections with T nuclei (VPL, VL, R) of the motor
representation of forelimb, followed by the representation of hindlimb, trunk
and, finally, the minimal projection of the representation of face and head. As
opposed to motor representation of the forelimb and also of the face and head,
with uniform distribution of fibers in VPL, VL and R, the number of efferents of
motor representation of hindlimb, passing in VL, was almost 2.5 time lower than
in VPL and R, whereas the representation of trunk had the predominant projection
to VL. Dominant cortico-thalamic connection suggests greater involvement of T
nuclei studied in the realization of functional specialization of certain
somatotopical representations of MI.
PMID- 27487658
TI - [REACTIVE CHANGES IN THE ASTROCYTES OF FOREBRAIN NUCLEUS ACCUMBENS AFTER
RESTRICTION OF BLOOD FLOW IN THE BASIN OF BOTH COMMON CAROTID ARTERIES IN RATS].
AB - Reactive changes of astrocytes were studied in forebrain nucleus accumbens in
rats (n = 12) after global cerebral ischemia induced by bilateral occlusion of
both common carotid arteries, which is a frequently used model to assess the
effectiveness of pharmacological agents that have anti-ischemic and
neuroprotective properties. Under these conditions, the nucleus accumbens was in
the area of partial ischemia. Morphometric study of nucleus accumbens was
performed in three groups of rats (4 animals in each group) after ligation of
both common carotid arteries, after a sham operation and in healthy animals.
Astrocytes were demonstrated in serial sections using the reaction to glial
fibrillary acidic protein counterstained with hematoxylin. 7 days after the
surgery, in each animal the number of astrocytes was counted in the sections in 7
successiive squares of 0.01 mm2 each, the distance between their bodies and the
capillary wall was measured within the circle of 20 MUm radius, the cell body
area and the length of their main processes were determined. It is found that
astrocytes in the nucleus accumbens in the model of bilateral occlusion of the
common carotid arteries for 7 days experienced a partial state of ischemia. Their
reactive changes were manifested by the signs of the cytotoxic edema, damaging
intermediate filament proteins in their bodies, processes and in the perivascular
glial membranes. The concentration of the astrocyte cell bodies near blood
capillaries is the adaptation mechanism and is a condition for the survival of
cells under the restriction of blood flow in the brain.
PMID- 27487659
TI - [LOCALIZATION AND QUANTITATIVE ASSESSMENT OF OXYGEN-DEPENDENT HYPOXIA-INDUCIBLE
FACTOR 1alpha IN THE BRAIN OF MITTEN CRAB ERIOCHEIR JAPONICA IN NORM AND IN ACUTE
ANOXIA (AN IMMUNOHISTOCHEMICAL STUDY)].
AB - Using immunoblotting and immunocytochemistry, the expression of hypoxia-inducible
factor 1alpha (HIF-1alpha) was studied in the brain of the mitten crab Eriocheir
japonica in norm and at 2, 4, 6 and 12 hours of anoxia on the model of water
deprivation. In intact crabs, the number of immunopositive neurons was small, but
it increased with anoxia duration. Particularly pronounced increase in the
proportion of neurons with the HIF-1alpha expression was found in cell group 6.
In group 9/11. the highest expression index was observed between 2-6 hours of
anoxia. In group 17, significant changes in the proportion of immunopositive
cells was observed only after 2 hours of anoxia. After 6 hours of anoxia,
proportion of neurons with HIF-1alpha expression within all cell groups was
reduced, but the reactions appeared in the blood cells. It is assumed that the
increase in the proportion of immunopositive neurons and the appearance of the
expression of HIF-1alpha in blood cells in the anoxic brain play an important
role in providing compensatory and protective processes, enhancing adaptive
capacity of mitten crab under the conditions of hypoxic stress.
PMID- 27487660
TI - [CELL CONTACT PROTEIN BETA-CATENIN IN EPENDYMAL AND EPITHELIAL CELLS OF THE
CHOROID PLEXUS OF THE CEREBRAL LATERAL VENTRICLES].
AB - The purpose of this study was to examine the distribution pattern of cellular
contacts protein beta-catenin in the choroid plexus and ependyma of lateral
ventricles of the brain. The study was conducted on frontal sections of the brain
of Wistar rats (n = 10) using polyclonal antibodies against beta-catenin. The
obtained preparations were analyzed by microscopy in transmitted light and using
confocal laser microscopy. To study the distribution of beta-catenin in different
projections, three-dimensional reconstruction was performed. The study
demonstrated different distribution patterns of this protein in ependyma and
choroid plexus. Unlike ependyma, in the cells of the choroid plexus beta-catenin
was distributed in the same way as in simple epithelial tissues (on the basal and
lateral borders of the cells). This may indicate different tissue attribution of
the ependyma and the choroid plexus epithelium, despite their common origin.
PMID- 27487661
TI - [EXPRESSION OF DOUBLECORTIN AND NeuN IN THE DEVELOPING CEREBELLAR NEURONS IN
RAT].
AB - This work was performed on the offspring of 5 outbred female albino rats to give
a comparative immunohistochemical evaluation of doublecortin (DCX) and NeuN
expression in the neurons of the cerebellar cortex and nucleus interpositus in
the early postnatal ontogenesis (postnatal days 2-15). DCX expression was
detected in postmitotic neurons of the external granular layer and migrating
neurons of the cerebellar cortex. At postnatal days 2 and 7 DCX expression in
neocerebellum was higher than in paleocerebellum. NeuN expression was found to
appear in migrating granule neurons, and reach the maximum in mature neurons of
internal granular layer. DCX expression was not detected in Purkinje cells and in
the nucleus interpositus of the cerebellum. In neurons of the nucleus
interpositus the expression of NeuN progressively increased from postnatal days 2
to 15. Thus, a comparative immunohistochemical study of the dynamics of the
expression of the pair of molecular markers studied proved to be an effective way
of the assessment of the development of granular neurons of the cerebellum in
early postnatal ontogenesis.
PMID- 27487662
TI - [CHARACTERISTICS OF THE RETINA IN CHRONIC STRESS IN LABORATORY RATS OF DIFFERENT
AGE GROUPS].
AB - The retina was studied in albino laboratory male rats of two age groups (12 and
24 months), 10 animals in each subjected to chronic combined stress. The stress
was caused in animals by simultaneous exposure to pulsed light, loud sound,
swinging and restriction of mobility for 7 days, 30 mm daily. The retina of
intact rats of the corresponding age groups (n = 20) served as control.
Enucleated eyes of stressed and control animals were processed with standard
histological technique and stained with Nissl's method and hematoxylin-eosin. The
retina of the stressed animals of both age groups showed the decrease in the
number of cells and the disarrangement of its layers, most pronounced in the
layers of photoreceptor neurons and ganglion cells. The comparative morphometric
analysis demonstrated a reduction of the layer thickness and cell numerical
density in the retina of stressed animals, both young (12 months) and old (24
months), as compared to that of control animals.
PMID- 27487663
TI - [CHANGES OF THE CONTENT OF DLL4 AND Jag-1 ANGIOGENESIS REGULATORS IN HUMAN DERMIS
IN ONTOGENESIS].
AB - The goal of this study was to examine the contents of D114 and Jag-1 angiogenesis
regulators in human dermis at different age periods. D114 and Jag-1 were
demonstrated by indirect immunohistochemistry in skin sections of fetuses of 20
40 gestational weeks and in persons aged from birth to 85 years. D114 was studied
in 150 skin samples of 72 females and 78 males, while Jag-1 was examined in 120
samples of 58 females and 62 males. It is found that the immunoreactivity was
mainly expressed by the endothelial cells. Vessels, which gave a positive
reaction to D114 and Jag-1, were found throughout the entire thickness of the
dermis, both in fetuses, and people of all age groups. Expression of D114 in the
vessels of dermal microvasculature was shown to increase from 20 weeks of
gestation to 20 years. With the further age increase, the intensity of the
reaction of blood vessels for D114 was decreased. Expression of Jag-1 in dermal
microvessels was enhanced from 20 weeks of gestation to 85 years. The results are
discussed in connection with the role of D114 and Jag-1 in angiogenesis in human
dermis during ontogeny.
PMID- 27487664
TI - [CLINICAL SIGNIFICANCE OF ANATOMICAL VARIABILITY OF THE LEFT INFERIOR PHRENIC
VEIN].
AB - The diaphragm was taken from the corpses of 80 humans of both sexes of adult age
and was studied using the complex of preparation, injection, morphometric and of
variational-statistical methods. A significant anatomical variation of the left
inferior phrenic veins was found, that was characterized by different variants of
their confluence, and variation of their diameters. Five variants of the
confluence of the left inferior phrenic veins were defined. It was shown that the
variant of confluence of the left inferior phrenic veins into a single trunk
fusing with the inferior vena cava was suitable for catheterization. Suitable for
catheterization left inferior phrenic veins may be divided into freely
catheterizable (diameter of 5 mm and more).and conditionally catheterizable
(diameter less Than 5 mm). When performing cardiac resynchronization therapy, the
vein can be used as an alternative way (along with the coronary sinus of the
heart) for transvenous delivery system of stimulation electrode. Variants of
confluence of the left inferior phrenic vein in hepatic and adrenal veins were
not suitable for catheterization.
PMID- 27487665
TI - [MORPHO-FUNCTIONAL CHANGES OF THYMUS TISSUES IN CHILDREN WITH CONGENITAL HEART
DISEASE].
AB - Biopsy specimens of the thymus were studied in children aged under 11 months (n =
77) with congenital heart defects and circulatory hypoxia of varying severity.
Histological sections were stained with hematoxylin-eosin and Shubich's method
(to demonstrate mast cells). The expression of Ki-67, CD3 and CD34 was assessed
by immunohistochemistry. The ultrastructure of thymic tissues was also examined.
It was found that the severity of hypoxia determined the morphological changes in
the organ associated with a development of large complex of tissue reactions. A
disruption of internal structure and a loss of integrity of epithelio-reticular
cells and thymocytes were demonstrated in ultrathin sections. Thymocyte
proliferation index (Ki-67) and thymocytopoiesis intensity (CD3+) were reduced in
all the zones of the thymus. The degree of hypoxia affected the redistribution of
CD3+ lymphocytes leading to their accumulation in the medulla. The processes of
endogenous regeneration took place which involved the cells of fibroblastic line
and progenitor cells (CD34+) together with active formation of new blood vessels.
These findings suggest that the morphological changes identified in the tissues
of the thymus are a manifestation of tissue adaptation to hypoxia of varying
severity under conditions of endogenous regeneration, simultaneously reflecting
the processes of substitution cytogenesis.
PMID- 27487666
TI - [MORPHOMETRIC AND HISTOCHEMICAL CHARACTERISTICS OF THE THYROID GLAND AFTER
ADMINISTRATION OF HYDRA PEPTIDE MORPHOGEN].
AB - The effect of Hydra peptide morphogen (HPM) on quantitative histochemical and
morphometric parameters of the thyroid gland (TG) was studied. The experiments
were conducted on 40 outbred albino male mice weighing 20-25 g, which were
injected intraperitoneally with HPM at the dose of 100 MUg/kg of body weight per
day for 5 days. Relative volumes occupied by the epithelium (E), including its
follicular (E(f)), interfollicular (E(i)) components, and colloid (C) were
determined using stereological method on TG transverse sections. E(f)/E(i) and
E/C ratios were calculated as the indices of follicular organization and TG
activity, respectively. Mitotic activity of thyrocytes was also evaluated. The
enzymes, characterizing the metabolic activity of thyrocytes: NADH-diaphorase,
succinate- and lactate dehydrogenases were demonstrated on cryostat sections of
material, frozen in liquid nitrogen and their activity was assessed
cytophotometrically. The results demonstrated that HPM administration lead to a
significant increase in relative volume of thyroid epithelium with a concomitant
reduction of the volume of the colloid. E(f)/E(i) ratio was not significantly
different from that in the control. HPM also induced a significant increase of
thyrocyte proliferation rate and of the activity of enzymes studied.
Collectively, the quantitative histoenzymological and morphometric data obtained
indicate the stimulating effect of HPM on TG functional activity and thyrocyte
proliferation.
PMID- 27487667
TI - [SUSTENTOCYTE NUMBERS IN THE NEONATAL PERIOD IN THE OFFSPRING OF FEMALE RATS WITH
EXPERIMENTAL LIVER DAMAGE].
AB - On serial histological sections of the testes, stained with hematoxylin-eosin,
using a morphometric device, the total numbers of spermatogenic cells and
sustentocytes (Sertoli cells) were measured in the convoluted seminiferous
tubules of neonatal rat pups. Experimental groups consisted of rats born from
females with experimental liver damage of various origins--autoimmune (n = 33),
toxic (n = 32), alcoholic (n = 12), and medicinal (n = 27). The control group
included pups born from normal female rats (n = 14). In experimental rats both
increase and decrease of the total number of sustentocytes was detected. In the
animals of most of the experimental groups, sustentocyte cell index reflecting
the ratio of the number of spermatogenic cells and sustentocytes, was decreased.
PMID- 27487668
TI - [INTERRELATION BETWEEN THE PREOPERATIVE MORPHOLOGICAL CHARACTERISTICS OF
PERIPHERAL BLOOD AND THE QUALITY OF ENGRAFTMENT OF VASCULARIZED ADIPO-FASCIO
CUTANEOUS FLAPS IN RATS].
AB - The aim of this work was to determine the interrelation between the preoperative
blood counts and the quality of vascularized adipo-fascio-cutaneous flap
survival. In 10 adult male Wistar rats, a flap with the area of 18 cm2 was formed
on the basis of superficial inferior epigastric artery; after a 90 min ischemic
period it was replanted. 12 days after operation the quality of flap survival was
assessed with computer-assisted planimetry. It was found that the combination of
preoperative leukocyte, thrombocyte, neutrophil and eosinophil counts as well as
reactive lymphocyte counts close to the maximal reference values increased the
probability of epidermolysis.
PMID- 27487669
TI - [MORPHOLOGICAL CHARACTERISTICS OF OSSEOINTEGRATION AFTERAPPLICATION OF TITANIUM
IMPLANTS WITH BIOACTIVE COATING AND RECOMBINANT BONE MORPHOGENETIC PROTEIN].
AB - Experiments were carried out on 22 albino male Wistar rats to study the
morphological peculiarities of osseointegration of titanium grafts with bioactive
surface stimulated additionally with bone plastic material "Gamalant-paste-FORTE
Plus" containing recombinant human bone morphogenetic protein-2 (rhBMP-2). In 9
rats the implants were placed into femoral bones after local treatment of bone
canal with rhBMP-2-containing material. Another 9 animals were implanted but
received no treatment, 4 rats formed the group of intact control. Zone of
osseointegration was studied 4, 8 and 12 weeks after graft placement using
histological and morphometric methods as well as immune histochemistry to
demonstrate osteonectin, CD68, MMP-9, and TIMP-1. The study showed that
preliminary treatment of bone canal with rhBMP-2-containing material preceding
implant placement was accompanied by an additional osteoinductive effect. More
intense and outrunning bone formation in the area of osseointegration was
observed, together with remodeling and compaction of the contiguous cancellous
bone, thus providing the necessary balance between MMP-9 and TIMP-1 with a high
level of each factor expression.
PMID- 27487670
TI - [CURRENT HISTOCHEMICAL METHODS OF TISSUE IRON DEMONSTRATION BASED ON PERLS'
REACTION].
AB - The article presents the information on the modern modifications of Perls'
reaction including diaminobenzidine enhancement according to R. Meguro (for
various tissues). M.A. Smith (for nervous tissue), S.M. Levine (for detection of
iron in oligodendrocytes and myelinated nervous fibers), and our own modification
for visualization of the nucleolar iron. The analysis is performed of the
advantages and disadvantages of these modifications of histochemical
demonstration of iron. It is shown that the use of new methodological approaches
significantly increases the sensitivity of Perls' reaction. Control procedures
allow to to eliminate the possibility of artifacts.
PMID- 27487671
TI - [The development of morphological research on the problem of gravitational
overload effect in S. M. Kirov Military medical Academy].
PMID- 27487672
TI - [Modern clinical anatomy, problems of its teaching and development in Russia].
PMID- 27487673
TI - [Not Available].
PMID- 27487674
TI - [Prevention and remission of diabetes: is it feasible?].
AB - Prevention of type 2 diabetes is a major public health objective in view of the
increasing prevalence of obesity in the population, the medical community and
politicians to develop preventive strategies as well as effective interventions
to induce remission of diabetes. Clinical studies indicate that intensive medical
treatment through lifestyle adaptations and even more bariatric surgery can
prevent or rather delay type 2 diabetes onset and factor remission but with a
positive effect which progressively decreases with time. Duration of diabetes and
weight loss are major prognostic factors. New strategies are necessary to improve
both short- and long-term efficacy of diabetes prevention and remission.
PMID- 27487675
TI - [Cardiovascular safety of antidiabetics].
AB - Type 2 diabetes is characterized by a high risk of micro- and macro-vascular
complications. Cardiovascular diseases are the leading cause of death of diabetic
patients. In this context, the search for molecules decreasing cardiovascular
mortality makes sense. Until the EMPA-REG OUTCOME study published late 2015,
showing a reduction of cardiovascular mortality of patients treated with
empagliflozin, an SGLT2 inhibitor, there was no molecule known to decrease
cardiovascular mortality. The purpose of this article is to review the various
existing antidiabetic molecules and their impact (positive/neutral/negative) on
cardiovascular mortality.
PMID- 27487676
TI - [Gestational diabetes--what are the non-medical approaches?].
AB - Gestational diabetes is a multifactorial disease that increases the risk for
complications for the mother and her child in the short and long term. The
perinatal period represents an opportunity not only to assist the mother in
improving her own health but also that of the future generation. This article
focuses on lifestyle and psychological aspects that form the base for non-medical
treatment approaches. Considering different risk factors separately is not
sufficient for the improvement of the metabolic and mental health of women with
gestational diabetes. With a multimodal interdisciplinary approach that includes
physical activity, dietary advice and psychological support, an improvement of
the health and well-being of both the mother and her child is expected. Future
studies are necessary to confirm this proposed care approach.
PMID- 27487677
TI - [Preventive measures of diabetic foot complications].
AB - Diabetic foot complications are a public health challenge and preventive measures
although simple are often not enforced, as evidenced by the lack of decrease in
the rate of ulcers and amputation in Switzerland. This article proposes a risk
score to grade individual risk of the diabetic patient and an individualized
prevention measures as this risk. We discuss the importance of collaboration of
various specialists. Two areas are important, first the early involvement of
specialists in revascularization because the diabetic population with feet at
risk of ulceration risk nowadays primarily has neuro-ichemic ulcerations and also
the close collaboration with podiatrists and orthopedic shoemakers who are full
partners of the multidisciplinary team.
PMID- 27487678
TI - [Insulin and oral antidiabetes drugs: how associate these treatments in
ambulatory care?].
AB - Type 2 diabetes mellitus is a complex and progressive metabolic disease involving
more than 400 millions of people worldwide. The treatments need to be constantly
managed to maintain appropriate glycemic control and avoiding complications.
There is a wide variety of therapeutic option including oral antidiabetes drugs
or new insulin on the market. The initiation of insulin treatment seems a
mandatory step for a large panel of patients. Therefore, it is important to know
the indications to initiate insulin treatment and the best way to associate it
with antidiabetes drugs.
PMID- 27487679
TI - [Use of new antidiabetics in the elderly population].
AB - Over the last few years, we have noticed the arrival on the market of new
antidiabetic treatments. These represent an potential advantage because of the
increase in the prevalence of type 2 diabetes, particularly in the elderly
population. Nevertheless, elderly patients have a number of frailties that should
be considered in the treatment of this condition. There is a lack of literature
in this population as elderly are frequently excluded from randomized controlled
trials. Therefore, guidelines were developed based on the consensus of experts in
geriatrics and diabetology for this specific population. We have to consider the
potential benefits and adverse effects of the new antidiabetics in older
patients.
PMID- 27487680
TI - [Not Available].
PMID- 27487681
TI - [Not Available].
PMID- 27487682
TI - [Not Available].
PMID- 27487683
TI - [Not Available].
PMID- 27487684
TI - [Not Available].
PMID- 27487685
TI - [Not Available].
PMID- 27487686
TI - [Not Available].
PMID- 27487687
TI - [Not Available].
PMID- 27487688
TI - [Not Available].
PMID- 27487689
TI - [Not Available].
PMID- 27487690
TI - [Not Available].
PMID- 27487691
TI - [Complication rates after amniocentesis in twin pregnancies: a case control study
and review of the literature].
AB - BACKGROUND: Twin pregnancies nave a nigner risk of fetal malformation than
singleton pregnancies. The literature suggests a higher risk of fetal loss
associated to amniocentesis in twin pregnancies compared to singleton ones.
However, published studies are very heterogeneous, rarely controlled or are not
taking into account many confounding factors. OBSERVATIONS: To assess all
complications that can be associated with amniocentesis in twin pregnancies.
MATERIALS AND METHODS: We collected retrospectively medical data concerning twin
pregnancies that underwent an amniocentesis in Erasme and Edith Cavell (IMEC)
hospitals in Brussels since February 2002. We compared all the complications to
those of twin pregnancies that haven't undertaken amniocentesis and singleton
pregnancies that underwent amniocentesis. The cases and control groups were
matched for age, parity and gestational age at the time of amniocentesis.
RESULTS: 94 cases of twin pregnancies that underwent amniocentesis (group I) were
included and compared to 94 twin pregnancies that haven't undertaken
amniocentesis and 94 singleton pregnancies that underwent amniocentesis. The rate
of intra-uterine growth restriction and pregnancies obtained by assisted
reproductive medicine was significantly higher in the group I for the latter, the
rate of late miscarriage was 2.1%, the rate of overall foetal loss is 2.68%, the
rate of overall preterm birth <= 37 SA was 59.3% (6.4% <= 28 SA and 29.8% <= 34
SA). These complications were not significantly higher than those of the control
groups after multivariable logistic regression analysis. CONCLUSION: Our data
showed no increased risk of foetal loss or preterm birth among twins that
underwent amniocentesis compared to controls.
PMID- 27487692
TI - [On the relationship between emotional dependency and abuse].
AB - Abuse is a complex psychosocial issue with multiple implications. This paper
takes a look at the physical and psychological manifestations of domestic
violence, i.e. between adult (romantic) partners as well as abuse of the elderly.
Past studies have looked at the relationship between emotional dependency, the
occurence and sustainability of abuse and the likehood that a victimized person
will terminate a relationship. Indeed, individuals with Dependent Personality
Disorder (DPD) or with dependent characteristics present a higher risk of
becoming abusive (both physically and mentally) as well as becoming a victim of
abuse. Regarding the elderly, the concept of "reverse violence"--where the
current abuser was the victim of the senior who is being abused-, also entails
dependent relationships. We identified three concepts that are necessary in the
understanding of how dependent relationships underpin abuse: Rusbult's model of
commitment in intimate relationships, the notion of dependency-possessiveness and
Murphy et al's notion of escalating affective dependency. Thus, it is imperative
that future studies in the field of domestic violence look at the dynamics of
dyads rather than the individuals alone.
PMID- 27487693
TI - [Management of Acute Gastroenteritis in Children].
AB - Acute gastroenteritis remains one of the most frequent disorders in infants and
children. The cornerstone of the treatment is oral rehydration, although the
latter does not reduce the duration of the diarrhea, which is about four days. As
a consequence, this quite benign condition of acute gastroenteritis in our
countries still does have an important socio-economic impact. Therefore, recent
European guidelines and recommendations consider the use of different medications
and agents that reduce the duration of diarrhea.
PMID- 27487694
TI - [Maturity onset diabetes of the young: just think about it].
AB - Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes with
onset in patients aged less than 25 years. It is a heterogeneous disorder due to
heterozygous monogenic mutations with an autosomal dominant transmission. It
could represent 2 to 5% of diabetes but is often under-diagnosed. We report three
different cases of MODY, two without associated abnormalities and one with renal
disorder. Mutations concern genes that are directly involved in the beta-cell
function. In patients with non-syndromic diabetes, more than 99% of MODY result
from mutations in hepatocyte nuclear factor-1-alpha (HNF-1-alpha ; formerly MODY
3), glucokinase (MODY 2), or HNF-4-alpha (MODY 1). The symptoms manifest slowly
with the absence of obesity and ketosis in most cases. MODY is usually treated by
diet, oral diabetes medications or insulin. Treatment and prognosis vary
depending on the genetic mutation. Clinicians should keep in mind the possibility
of MODY, especially in antibody-negative youth with familial diabetes. Making a
diagnosis of MODY may have important implications for the guidance of appropriate
treatment, prognosis and genetic counselling.
PMID- 27487695
TI - [Transdural spinal cord herniation: A rare cause of Brown-Sequard syndrome].
AB - We report a rare case of thoracic spinal cord herniation due to a defect of the
anterior dura mater causing a progressive myelopathy. This case, illustrated by
magnetic resonance and surgical imageries, will make the reader aware of this
entity and then prevent misdiagnosis.
PMID- 27487696
TI - [A 38 years old female with inflammatory myofibroblastic tumor and lactic
acidosis].
AB - Inflammatory myofibroblastic tumors (IMT) are rare tumors. They were originally
described in the lung, but they have been now observed in many others locations,
mainly abdominal and pelvic. These tumors are usually benign but their recurrent
nature and the presence of an abnormality of chromosome band 2p23 in some of
them, suggest that some lesions form a true tumor entity. Surgical excision as
complete as possible is the gold standard treatment. We report the case of a 38
years old female, who presented a recurrent metastasizing inflammatory
myofibroblastic tumor causing lactic acidosis and other biological abnormalities
such as hypercalcemia, hypoalbuminemia, hypoglycemia, disseminated intravascular
coagulation and inflammatory syndrome.
PMID- 27487697
TI - [Bilateral adrenal hemorrhage (BAH): cannabis and vascular involvement].
AB - We report the case of a 39-year-old man with bilateral adrenal haemorrhage. The
diagnosis is rarely primarily made with imaging alone. Our patient had a previous
history of a stroke six years prior to this episode. We evoke the possibility
that long-term daily cannabis use could be the underlying cause of the patient's
vascular pathologies. After thorough review of existing literature, this link was
found to be probable. Cannabis is the most consumed recreational drug in the
world, and this tendency is ever-increasing. Serious complications other than
psychiatric resulting from consumption are reported with increasing frequency.
Neurological, cerebrovascular, cardiovascular and respiratory complications have
been observed. It is thus important to remain vigilant when patients are
hospitalised notably through the emergency department, in order to obtain a
complete anamnesis, optimise screening, and to adapt the treatment of these
patients.
PMID- 27487698
TI - [Parietal seeding of HCC after percutaneous radiofrequency thermal ablation].
PMID- 27487699
TI - [History of pneumology in antiquity (part 2)].
AB - Nowadays, Hippocrate, "The Father of Medicine", still influences our medicine. He
was famous because of the great medical corpus texts preserved in his name. Only
recently, our universities have updated the famous Hippocratic Oath to avoid
contradictions with our modern ethics. Hippocrate was a great clinician but a
poor anatomist. Hippocratical humourism remained accurate until the age of the
enlightenment (18th century). Furthermore, it is difficult to distinguish
medicine from philosophy in Greek antiquity. So we have to contextualize Greek
ancient medicine in this philosophical field. In the 3rd century before Christus
(BC), the centre of gravity in medicine shifted to Alexandria. Indeed, a famous
academic library was created in 288 BC. At the same time, dissection of human
cadavers was authorized until the first century BC. This enabled the evolution of
the knowledge in anatomy and physiology. Rome was still polytheistic population
until the end of ancient times. Rome integrated Greek gods in his pantheon.
Asclepios became Aesculapius. Rome despises physicians in the first ancient age
of Rome. The family's father provided medical cares. A lot of Greek physicians
settled then in Rome. Again, roman medicine grew in parallel with philosophical
trends. These trends were called "sects" but in fact, they were rather medical
schools. In this review, we will especially talk about three physicians of this
period: Aurelius Cornelius Celsus, Aretee of Cappadocia and Galenus of Pergamon.
Thereafter, medical knowledge did not really change significantly until
Renaissance period.
PMID- 27487700
TI - [Not Available].
PMID- 27487701
TI - Doing Harm: Physicians, Enemy Combatants, and Torture.
PMID- 27487703
TI - Whom We Look Up To.
PMID- 27487702
TI - What if Policy Makers Used Evidence When Legislating? A Case Study With
Maryland's Unique Compounding Law.
PMID- 27487704
TI - Introduction.
PMID- 27487705
TI - Will Clinical Practice Guidelines Protect Against Malpractice Risk?
PMID- 27487706
TI - Emergency Care in Maryland: The Expanding Role of Evidence Based Medicine and the
Medicare Waiver.
AB - The 2014 Maryland Medicare Waiver alters the reimbursement model by transitioning
from fee-for-service to global payments for hospitals. This increases the need
for hospital-based emergency departments to become more cost-conscious,
particularly regarding high-cost imaging and admission decisions. Evidence based
medicine offers a potential solution to achieve these aims. Development and use
of validated clinical decision rules and care pathways can reduce unnecessary
testing and reduce hospital admissions where a patient could be treated as an
outpatient. Paired with functional systems incorporating alternative care
pathways and health information technology, clinical decision rules can reduce
cost without sacrificing patient safety or experience.
PMID- 27487707
TI - The Emperor's New Boards: (Or How I Learned To Stop Worrying and Love That Test).
PMID- 27487708
TI - What's the Evidence for Evidence Based Medicine?
PMID- 27487709
TI - The Trial: A Medical Allegory.
PMID- 27487710
TI - Physician Volunteerism: Making a Difference One Patient at a Time.
PMID- 27487711
TI - Final Words.
PMID- 27487712
TI - [MESSAGE FROM THE TRUSTEES].
PMID- 27487713
TI - [Ocular Manifestations Induced by Diversification of Anticancer Agents--Focus on
Corneal Disorders].
PMID- 27487714
TI - [Guide for Clinical Use of Hydroxychloroquine].
PMID- 27487715
TI - [Intravitreal Triamcinolone Acetonide for Persistent Diabetic Macular Edema after
Vitrectomy].
AB - PURPOSE: To determine whether intravitreal triamcinolone acetonide (IVTA) is
effective in resolving edema in eyes with persistent diabetic macular edema (DME)
after vitrectomy. PATIENTS AND METHODS: Sixteen eyes of 16 patients were given 4
mg IVTA after vitrectomy for DME. The best-corrected visual acuity (BCVA),
central macular thickness (CMT), and average threshold (AT) of the central retina
were determined during the 24 weeks follow-up period. Patients were divided into
two groups; early treatment group and late treatment group. RESULTS: The BCVA was
significantly improved at 12 weeks, the CMT was significantly improved at 24
weeks, and the AT was significantly improved at 4 weeks after IVTA (repeated
ANOVA, p < 0.05). The BCVA was more significantly improved in the early treatment
group than in the late treatment group at 4 and 12 weeks (unpaired t test, p <
0.05). CONCLUSION: Our results indicate that IVTA should be considered as
treatment for patients with persistent DME after vitrectomy, especially with
early treatment patients.
PMID- 27487716
TI - [Efficacy and Safety of A0001 (Brilliant Blue G250) for Internal Limiting
Membrane Staining and Peeling: Phase III Investigator-initiated Multicenter
Clinical Trial].
AB - PURPOSE: To investigate the efficacy and safety of A0001 (brilliant blue G250)
for visualization of the internal limiting membrane (ILM) during and after
vitrectomy. METHODS: Patients (n = 31) requiring ILM peeling during vitrectomy
were enrolled in this clinical trial. After injection of A0001 (range: 0.0625 to
0. 125 mg), the staining grade and the peeling ease of the ILM were evaluated in
five steps (levels 0 to 4). The safety of A0001 was investigated for 7 days after
surgery. RESULTS: From the evaluation of a primary endpoint by the Independent
Data Monitoring Committee (IDMC) and a secondary endpoint by each surgeon, A0001
was effective in all cases at three or more levels ( >= level 2 was defined as
effective) for evaluation of the grade of visualization and operating ease.
Adverse events occurring in two or more cases included elevated intraocular
pressure, eye pain, eye discharges, and retinal bleeding. One serious adverse
event was a case of unclosed macular hole after vitrectomy, but the patient
recovered after reoperation. CONCLUSIONS: A0001 was effective and safe for
visualization of the ILM during vitrectomy, and there was an improvement in ease
of operation.
PMID- 27487718
TI - [Japan Cornea Conference 2016].
PMID- 27487717
TI - [A Case of a Corneal Disorder after Breast Cancer Treatment with Nab-paclitaxel].
AB - BACKGROUND: We report a case of a corneal disorder after breast cancer treatment
with a microtubule inhibitor, nab-paclitaxel (Abraxane). CASE: A 55-year-old
woman, who was referred to our clinic, presented with blurred vision. 2 weeks
previously, she had been undergoing treatment with nab-paclitaxel, trastuzumab
and pertuzumab. Visual acuity was 20/60 in right eye and 20/40 in left eye. Slit
lamp examination showed an atypical epithelium invasion of the cornea in both
eyes and small epithelial defect in left eye. After the nab-paclitaxel treatment
was discontinued the corneal findings improved. 4 months later, visual acuity was
20/15 in right eye and 20/20 in left eye. CONCLUSIONS: Nab-paclitaxel can cause
severe corneal disorders, but the possibility that trastuzumab and pertuzumab
combination therapy is associated with these disorders cannot be denied.
Clinicians should consider the possibility of the side effects caused by systemic
administration in cases of corneal disorders of uncertain etiology.
PMID- 27487719
TI - [PROGRESS REPORT FROM THE STRATEGIC PLANNING COMMITTEE].
PMID- 27487720
TI - [EDITOR'S NOTE].
PMID- 27487721
TI - Prospects and progress in cell therapy for acute respiratory distress syndrome.
AB - INTRODUCTION: Despite progress in understanding the pathophysiology of the acute
respiratory distress syndrome (ARDS), it remains a devastating clinical disorder
associated with high mortality rates, and those who survive can experience
significant long-term morbidity. Recent advances in the management of ARDS have
mostly been achieved in supportive care, including the use of protective
mechanical ventilation, neuromuscular blocking agents, prone positioning, and
conservative fluid strategies. However, to date, no pharmacologic therapy has
been able to act effectively on disease-specific pathways or to reduce mortality.
In this context, current advances in understanding the potential roles of
alternative approaches, such as cell therapy, offer new hope for ARDS. AREAS
COVERED: This review discusses the use of mesenchymal stromal (stem) cells (MSCs)
in pre-clinical experimental models of ARDS and in ongoing clinical trials.
EXPERT OPINION: Through the secretion of soluble mediators and extracellular
vesicles, MSCs have been shown to modulate inflammation, enhance bacterial
clearance, and reduce organ injury and death, making them a potential novel
treatment for ARDS. Initial clinical trials have demonstrated the safety of MSC
administration in patients with ARDS but further investigations are required to
further characterize the efficacy profile of these therapies.
PMID- 27487722
TI - Bioassay Development for Ultrasensitive Detection of Influenza A Nucleoprotein
Using Digital ELISA.
AB - Flu is caused by the influenza virus that, due to mutations, keeps our body
vulnerable for infections, making early diagnosis essential. Although immuno
based diagnostic tests are available, they have low sensitivity and
reproducibility. In this paper, the prospect of detecting influenza A virus using
digital ELISA has been studied. To appropriately select bioreceptors for this
bioassay, seven commercial antibodies against influenza A nucleoprotein were
methodically tested for their reactivity and binding affinity. The study has been
performed on two markedly different platforms, being an enzyme-linked
immunosorbent assay and a surface plasmon resonance system. The selected
antibodies displayed completely different behavior on the two platforms and in
various assay configurations. Surprisingly, the antibodies that showed overall
good reactivity on both platforms had the highest dissociation constant among the
tested antibodies, suggesting that, although important, binding affinity is not
the only parameter to be considered when selecting antibodies. Moreover, only one
antibody had the capacity to capture the nucleoprotein directly in lysis buffer
used for releasing this viral protein, which might pose a huge advantage when
developing assays with a fast time-to-result. This antibody was implemented on an
in-house developed digital ELISA platform for ultrasensitive detection of
recombinant nucleoprotein, reaching a detection limit of 4 +/- 1 fM in buffer and
10 +/- 2 fM in 10-fold diluted nasopharyngeal swabs, which is comparable to
currently available fast molecular detection techniques. These results point to a
great potential for ultrasensitive immuno-based influenza detection.
PMID- 27487724
TI - Single-Step Nanoporation of Water-Immersed Polystyrene Film by Gaseous
Nanobubbles.
AB - Nanoporation of planar polystyrene (PS) film by gaseous nanobubbles is described.
Ambient gas (air) surface nanobubbles are used to create rounded nanopinholes in
supported ultrathin PS films immersed in water. Nanoporation proceeds under
biocompatible conditions-in deionized water at room temperature (20 degrees C)
in the absence of any high-energy-demanding processes, in a single step triggered
by short (5 s) moderate pressure drop (Deltap ~ -10 kPa) applied on an aqueous
phase. Atomic force microscopy (AFM) analysis shows a relatively narrow
dimensional distribution, with the prevailing nanopinhole radius of 10 nm and
uniform spread with an appearance density of ~600/MUm2. The nanoporation
mechanism is discussed. "Nanobubble/tip-assisted" nanoindentation phenomenon is
observed based on the compounded interaction of the surface nanobubble with the
AFM tip upon prolonged in situ nanobubble scanning.
PMID- 27487723
TI - Systematic Early Intervention for Bereaved: Study Protocol of a Pilot Randomized
Controlled Trial With Families Who Suddenly Lose a Partner and a Parent.
AB - BACKGROUND: Grief has been associated with several long-term negative outcomes
for both surviving parents and bereaved children, especially when it is preceded
by unnatural and violent deaths. Nevertheless, it has been an underestimated
public health problem with few, if any, empirically documented early preventive
intervention programs. The best time to start them is also a major question that
requires further evidence. OBJECTIVE: The overall aim of this study is to assess
the feasibility of a future larger trial, informing sample size calculation,
recruitment/randomization procedures, retention rates, data collection forms, and
outcomes. This study will also explore: (1) the early effects of Systematic Early
Intervention for Bereaved (SEIB) compared with the early effects of care as
usual, and (2) the effects of the immediate SEIB version compared with the
effects of the delayed SEIB version. METHODS: In a pilot randomized controlled
trial (RCT) with a delayed intervention design, suddenly bereaved families will
be assigned to: the immediate-SEIB intervention group, or the delayed-SEIB
intervention group. Participants will fill in a set of self-report measures at
baseline, and after 3, 6, and 9 months follow-up. Quantitative data on traumatic
stress symptoms, complicated grief, psychological wellbeing, daily functioning,
social support, parental capacity, parenting practices, and family functioning
will be collected to inform power calculations and explore SEIB's preliminary
effects. Data on the flow of participants throughout the trial will be analyzed
in order to estimate recruitment and retention rates. Two brief questionnaires
were developed to assess recruitment procedures, randomization, and data
collection materials. RESULTS: Recruitment for this project started in August
2015, and follow-up data collection will be completed in June 2017. CONCLUSIONS:
This study prepares the ground work for the design and implementation of a main
trial and may add preliminary knowledge to the significance of early supportive
practices that have been commonly used regardless of their sparse evidence.
PMID- 27487725
TI - Chromatin remodelling and antisense-mediated up-regulation of the developmental
switch gene eud-1 control predatory feeding plasticity.
AB - Phenotypic plasticity has been suggested to act through developmental switches,
but little is known about associated molecular mechanisms. In the nematode
Pristionchus pacificus, the sulfatase eud-1 was identified as part of a
developmental switch controlling mouth-form plasticity governing a predatory
versus bacteriovorous mouth-form decision. Here we show that mutations in the
conserved histone-acetyltransferase Ppa-lsy-12 and the methyl-binding-protein Ppa
mbd-2 mimic the eud-1 phenotype, resulting in the absence of one mouth-form.
Mutations in both genes cause histone modification defects and reduced eud-1
expression. Surprisingly, Ppa-lsy-12 mutants also result in the down-regulation
of an antisense-eud-1 RNA. eud-1 and antisense-eud-1 are co-expressed and further
experiments suggest that antisense-eud-1 acts through eud-1 itself. Indeed,
overexpression of the antisense-eud-1 RNA increases the eud-1-sensitive mouth
form and extends eud-1 expression. In contrast, this effect is absent in eud-1
mutants indicating that antisense-eud-1 positively regulates eud-1. Thus,
chromatin remodelling and antisense-mediated up-regulation of eud-1 control
feeding plasticity in Pristionchus.
PMID- 27487726
TI - Postoperative Changes in Strabismus, Ductions, Exophthalmometry, and Eyelid
Retraction After Orbital Decompression for Thyroid Orbitopathy.
AB - INTRODUCTION: Surgical rehabilitation of thyroid orbitopathy involves reducing
proptosis, treating strabismus, lengthening the eyelids, and managing aesthetic
changes. Not all are necessary in each patient; however, they often are. The
current investigation intends to describe postdecompression changes that may
influence the staging of these procedures. METHODS: In this retrospective cohort
study, records of 169 patients who underwent orbital decompression between 1983
and 2001 were reviewed. A single orbital specialist confirmed all measurements.
Time to follow up was defined as the most recent follow up after decompression
and prior to any secondary procedures. No strabismus or eyelid surgery was
performed at the time of decompression. Strabismus was measured with alternating
prism cover test. Ductions were estimated utilizing Hirschberg's method.
Exophthalmometry was measured with Hertel. Eyelid positions were defined relative
to the pupillary light reflex. Strabismus data were analyzed within eye pairs.
Ductions, exophthalmometry and eyelid position were analyzed for each eye. T-test
for paired data was utilized to compare means pre- and postoperatively. RESULTS:
The study population was on average 45 years old and 73.4% women. Average length
of follow up was 1.2 years. Esotropia was significantly increased after
decompression by an average of 8.1 prism diopters (p < 0.01). Exotropia and
vertical deviations were not significantly altered. Ductions decreased by >5
degrees in at least one meridian for 68.1% of the population. Upper eyelid
retraction remained unchanged; however, lower eyelid retraction improved by 50%
from 1.4 mm to 0.7 mm (p < 0.01). Exophthalmometry improved from 23.5 mm to 19.7
mm (p < 0.01), and this result was correlated with the number of walls removed
(Pearson r = -0.302, p < 0.01). CONCLUSIONS: On average, esotropia and ductions
tend to worsen with decompression surgery. This result supports the clinical
dictum to avoid strabismus surgery until after decompression. The improvement in
lower eyelid retraction suggests that at least lower eyelid-lengthening surgery
should be reserved for after decompression, as there may be significant
spontaneous improvement, while the same may not be true for upper eyelid
retraction, which does not tend to change with decompression.
PMID- 27487727
TI - A Conjunctival Melanoma Causing Bloody Tears.
PMID- 27487728
TI - Globe Tenting Due to Displaced Lateral Orbital Wall Fragment.
PMID- 27487729
TI - Bacterial Biofilms in Jones Tubes.
AB - PURPOSE: To investigate the presence and microbiology of bacterial biofilms on
Jones tubes (JTs) by direct visualization with scanning electron microscopy and
polymerase chain reaction (PCR) of representative JTs, and to correlate these
findings with inflammation and/or infection related to the JT. METHODS: In this
study, prospective case series were performed. JTs were recovered from
consecutive patients presenting to clinic for routine cleaning or recurrent
irritation/infection. Four tubes were processed for scanning electron microscopy
alone to visualize evidence of biofilms. Two tubes underwent PCR alone for
bacterial quantification. One tube was divided in half and sent for scanning
electron microscopy and PCR. Symptoms related to the JTs were recorded at the
time of recovery. RESULTS: Seven tubes were obtained. Five underwent SEM, and 3
out of 5 showed evidence of biofilms (60%). Two of the 3 biofilms demonstrated
cocci and the third revealed rods. Three tubes underwent PCR. The predominant
bacteria identified were Pseudomonadales (39%), Pseudomonas (16%), and
Staphylococcus (14%). Three of the 7 patients (43%) reported irritation and
discharge at presentation. Two symptomatic patients, whose tubes were imaged
only, revealed biofilms. The third symptomatic patient's tube underwent PCR only,
showing predominantly Staphylococcus (56%) and Haemophilus (36%) species. Two of
the 4 asymptomatic patients also showed biofilms. All symptomatic patients
improved rapidly after tube exchange and steroid antibiotic drops. CONCLUSIONS:
Bacterial biofilms were variably present on JTs, and did not always correlate
with patients' symptoms. Nevertheless, routine JT cleaning is recommended to
treat and possibly prevent inflammation caused by biofilms.
PMID- 27487730
TI - Intracellular Elemental Patterns of Apoptosis Resistance in Transdifferentiated
Androgen-Dependent Prostatic Carcinoma Cells.
AB - The acquisition of neuroendocrine (NE) characteristics by prostate cancer (PC)
cells relates to tumor progression and hormone resistance. PC cells may survive
and function in androgen-deprived environments, where they could establish
paracrine signaling networks, providing stimuli for the propagation of local
carcinoma cells. We previously demonstrated, using electron probe X-ray
microanalysis (EPXMA), in LNCaP, PC-3, and Du 145 cell lines that apoptosis is
associated with intracellular elemental changes, and that the NE secretory
products, bombesin and calcitonin, inhibit etoposide-induced apoptosis, as well
as some of these elemental changes. In this study, LNCaP cells were induced in
vitro to transdifferentiate under androgen deprivation, to mimic the role of NE
cells in the apoptotic activity of transdifferentiated androgen-dependent PC
cells. Changes in intracellular ion content associated with apoptosis, assessed
by EPXMA, demonstrate that the transdifferentiated LNCaP cells are resistant to
etoposide-induced apoptosis and also to the etoposide-induced elemental changes.
The aggressive malignant potential of PC with neuroendocrine differentiation,
associated with hormonal independence, is partly because of the ability that most
NE tumor cells have to escape apoptosis, which can enhance the malignant
properties of tumor cells and may have therapeutic implications as tumor cells
are usually resistant to cytotoxic drugs as etoposide.
PMID- 27487731
TI - Radiation-induced solidification of ionic liquid under extreme electric field.
AB - An extreme electric field on the order of 10(10) V m(-1) was applied to the free
surface of an ionic liquid to cause electric-field-induced evaporation of
molecular ions from the liquid. The point of ion emission was observed in situ
using a TEM. The resulting electrospray emission process was observed to create
nanoscale high-aspect-ratio dendritic features that were aligned with the
direction of the electric field. Upon removal of the stressing field the features
were seen to remain, indicating that the ionic liquid residue was solidified or
gelled. Similar electrospray experiments performed in a field-emission scanning
electron microscope revealed that the features are created when the high-energy
electron beam damages the molecular structure of the ionic liquid. While the
electric field does not play a direct role in the fluid modification, the
electric stress was critical in detecting the liquid property change. It is only
because the electric stress mechanically elongated the fluid during the
electrospray process and these obviously non-liquid structures persisted when the
field was removed that the damage was evident. This evidence of ionic liquid
radiation damage may have significant bearing on electrospray devices where it is
possible to produce high-energy secondary electrons through surface impacts of
emitted ions downstream of the emitter. Any such impacts that are in close
proximity could see reflected secondary electrons impact the emitter causing
gelling of the ionic liquid.
PMID- 27487732
TI - Cerebrospinal Fluid Chemokine (C-C Motif) Ligand 2 Is an Early-Response Biomarker
for Blast-Overpressure-Wave-Induced Neurotrauma in Rats.
AB - Chemokines and their receptors are of great interest within the milieu of immune
responses elicited in the central nervous system in response to trauma. Chemokine
(C-C motif)) ligand 2 (CCL2), which is also known as monocyte chemotactic protein
1, has been implicated in the pathogenesis of traumatic brain injury (TBI), brain
ischemia, Alzheimer's disease, and other neurodegenerative diseases. In this
study, we investigated the time course of CCL2 accumulation in cerebrospinal
fluid (CSF) after exposures to single and repeated blast overpressures of varied
intensities along with the neuropathological changes and motor deficits resulting
from these blast conditions. Significantly increased concentrations of CCL2 in
CSF were evident by 1 h of blast exposure and persisted over 24 h with peak
levels measured at 6 h post-injury. The increased levels of CCL2 in CSF
corresponded with both the number and intensities of blast overpressure and were
also commensurate with the extent of neuromotor impairment and neuropathological
abnormalities resulting from these exposures. CCL2 levels in CSF and plasma were
tightly correlated with levels of CCL2 messenger RNA in cerebellum, the brain
region most consistently neuropathologically disrupted by blast. In view of the
roles of CCL2 that have been implicated in multiple neurodegenerative disorders,
it is likely that the sustained high levels of CCL2 and the increased expression
of its main receptor, CCR2, in the brain after blast may similarly contribute to
neurodegenerative processes after blast exposure. In addition, the markedly
elevated concentration of CCL2 in CSF might be a candidate early-response
biomarker for diagnosis and prognosis of blast-induced TBI.
PMID- 27487733
TI - Protective effects of glycyrrhizic acid from edible botanical glycyrrhiza glabra
against non-alcoholic steatohepatitis in mice.
AB - Non-alcoholic steatohepatitis (NASH) is a syndrome with simultaneous severe
hepatic steatosis, lobular inflammation and pericelluar fibrosis. The purpose of
the present study is to investigate the protective effect of glycyrrhizic acid
(GA), a natural triterpene glycoside from edible botanical glycyrrhiza glabra, on
NASH induced by a methionine and choline-deficient (MCD) diet in mice, and
further to elucidate the mechanisms of GA protection. Serum ALT and AST assay and
H&E staining were used to identify the amelioration of the liver
histopathological changes. Serum and hepatic lipid assay and Oil Red O staining
were used to measure lipid accumulation. Hepatic inflammatory and fibrosis gene
determination, as well as Mason Trichrome and Sirius Red staining were used to
determine the reduction of hepatic inflammation and pericelluar fibrosis.
Quantitative real-time PCR and Western blot assays were used to elucidate the
mechanisms underlying GA protection. The results indicated that GA treatment
reduced hepatic lipogenesis through a decrease in hepatic levels of SREBP-1c,
FAS, ACC1 and SCD1, and increased lipid metabolism through an induction of
PPARalpha, CPT1alpha, ACADS and LPL. GA also reduced hepatic inflammation via a
decrease in the expression of the hepatic inflammatory genes MCP-1 and VCAM-1. In
addition, GA reduced liver fibrosis through limiting HSC activation and collagen
deposition. In conclusion, GA produces a markedly protective effect against NASH
induced by a methionine and choline-deficient (MCD) diet in mice.
PMID- 27487734
TI - Clonal Origin of Hepatocellular Carcinoma and Recurrence After Liver
Transplantation.
AB - BACKGROUND This study aimed to determine whether patterns of tumor clonal origin
in pluri-nodular hepatocellular carcinoma (PNHC) could serve as an indicator of
tumor recurrence following liver transplantation. MATERIAL AND METHODS Tumor
tissue samples from 60 PNHC patients who underwent liver transplantation were
examined. The diagnosis of patients conformed to the University of California San
Francisco (UCSF) standards for pluri-nodular hepatocellular carcinoma. We
performed loss of heterozygosity tests at multiple microsatellite sites to
determine the clonal origins of the tumors. Clinical information, pathological
data, preoperative serum alpha-feto protein (AFP) and postoperative follow-ups
were obtained and correlations between the clonal origin of the tumor, tumor-free
survival, pathological characteristics, and AFP levels in serum were studied.
RESULTS A total of 165 tumor nodules were collected. Tumor clonal origins were
identified as intrahepatic metastasis (IM; 41.67%), multicentric occurrence (MO;
55%) or unidentified (3.33%). Three-year tumor-free survival for the IM group was
48% compared to 75.76% in the MO group (p<0.05), while the occurrence of
microscopic tumor thrombus was 100% and 3.03% (p<0.05) for these groups,
respectively. The degree of tumor differentiation was 80% for the IM group and
18.18% for the MO group (p<0.05), while the mean AFP concentration for these
groups was 226.80 MUg/L (2.78-3000 MUg/L) and 24.59 MUg/L (1.16-531. 30 MUg/L;
p<0.05), respectively. CONCLUSIONS Clonal origin patterns can serve as important
indicators to predict the recurrence of PNHC following liver transplantation.
Taken together with pathological characteristics and preoperative serum AFP
levels, the risk of recurrence can be established in advance.
PMID- 27487735
TI - Bath-related thunderclap headache: Case report of a male patient.
AB - Bath-related thunderclap headache (BRTH) is a rare entity, closed to reversible
cerebral vasoconstriction syndrome. It is only described in middle-aged women and
mainly Asiatic ethnic origins. Role of estrogen is consequently discussed. We
report here a case of a 36-year-old man, admitted for five episodes of
thunderclap headaches, triggered by hot shower. This is the first male case of
BRTH, opposing only a hormonal hypothesis. Furthermore, this African patient
consolidates the non-exclusivity of this affection to Asian ethnic origins.
PMID- 27487736
TI - Osteochondral Autograft Transfer Versus Microfracture in the Knee: A Meta
analysis of Prospective Comparative Studies at Midterm.
AB - PURPOSE: To compare microfracture (MFX) and osteochondral autograft transfer
(OAT) surgical techniques to determine (1) postoperative activity level, (2)
subjective patient outcomes, (3) failure rates, and (4) assess if any lesion
characteristics favored one technique over the other. METHODS: A comprehensive
review of literature was performed of all studies comparing MFX and OAT. Studies
included were all prospective studies that reported on activity-based outcome
measures such as Tegner activity scores and subjective outcomes such as the
International Knee Documentation Committee score. Failure rates, as determined by
the publishing authors, were recorded for each study. Meta-analyses were
conducted using a random-effects model. Paired standardized mean differences
(Hedges's g to account for small sample bias) were used for continuous outcome
measures, and risk ratios (Mantel-Haenszel method for small sample bias) for
dichotomous outcome measures. RESULTS: Six prospective studies satisfied the
eligibility criteria and included 249 patients (186 male, 120 female) with an
average age of 26.4 years and follow-up of 67.2 months. Tegner scores were
superior in patients treated with OAT compared with MFX (DeltaOAT-MFX for pre
post scores = 0.94 Tegner points, standardized mean difference [SMD] = 0.469, P =
.005). Failure rates of MFX were higher than OAT (OAT = 11%, MFX = 32%, risk
ratio = 2.42, P < .036). OAT was superior to MFX at 3 years in relation to
subjective outcome scores (SMD = 0.404, P = .008). When assessing OAT lesions
larger than 3 cm2, OAT was superior to MFX with respect to activity level (SMD =
0.506, P = .001). CONCLUSIONS: OAT may achieve higher activity levels and lower
risk of failure when compared with MFX for cartilage lesions greater than 3 cm2
in the knee, although there was no significant difference for lesions less than 3
cm2 at midterm. However, because of variability in patient-specific factors such
as age, preinjury activity level, lesion location and size, the superiority of
OAT over MFX cannot be generalized to all patient populations and therefore
requires individualized patient care. LEVEL OF EVIDENCE: Level II, meta-analysis
of Level I and II studies.
PMID- 27487737
TI - The True Recurrence Rate and Factors Predicting Recurrent Instability After
Nonsurgical Management of Traumatic Primary Anterior Shoulder Dislocation: A
Systematic Review.
AB - PURPOSE: To (1) define the cumulative recurrence rate after primary anterior
shoulder dislocation in Level I and II comparative studies and (2) to pool risk
ratios for common risk factors to provide a clinically practical hierarchy of
modifiable and nonmodifiable risk factors for recurrence. METHODS: Level I and II
prognostic studies were identified using the electronic databases CINAHL, Embase,
and MEDLINE from inception to December 2014. Included studies (n = 15) had
recurrent dislocation as the main outcome, and a minimum 2-year follow-up. The
cumulative odds ratio of prognostic factors was calculated where appropriate.
Bias was assessed in each study using the Quality in Prognosis Studies (QUIPS)
tool. RESULTS: The reported rate of recurrence ranged from 19% to 88% (pooled
overall = 21%; pooled Level I only = 47%). The pooled time to recurrence was 10.8
months (standard deviation 0.42). Male sex (n = 6 studies) conferred a 2.68 (1.66
4.31; P < .001) and patient age <20 years (n = 4 studies) conferred a 12.76 (5.77
28.2; P < .001; vs >20 years) increased odds of recurrence. An associated greater
tuberosity fracture (n = 7 studies) decreased the odds of recurrence by 3.8 times
(2.94-5.00; P < .001). The quality of evidence was moderate for age, low for sex,
and very low for all other prognostic variables. CONCLUSIONS: The pooled rate of
recurrence after primary anterior shoulder instability was found to be 21% among
moderate- to high-quality prognostic studies. Male sex and younger age predicted
a significantly higher risk of recurrent instability (approaching 80%), whereas
concurrent fracture of the greater tuberosity significantly decreased the risk of
subsequent recurrent dislocation. However, considering the quality of available
evidence for these predictors, there remains a clear need for further high
quality prospective studies. LEVEL OF EVIDENCE: Level II, systematic review of
Level I and II prognostic studies.
PMID- 27487738
TI - Genetic Analysis of Mismatch Repair Genes Alterations in Extramammary Paget
Disease.
AB - Extramammary Paget disease (EMPD) is a rare cutaneous malignant neoplasm. The
familial occurrence of EMPD and the high risk of concomitant secondary tumors in
EMPD patients have gained much attention. These findings highlight the importance
of genetic alterations in the tumorigenesis of this skin cancer. Genetic tests
and functional analysis of mismatch repair (MMR) genes were performed in EMPD.
The results showed that 8 of 20 cases with germline MMR genes mutations and 5 of
them exhibited microsatellite instability (MSI). Immunohistochemical staining
showed that the tumor tissues from 20 patients had the normal expression of MLH1
but 5 cases had the reduced expression of MSH2. There is a nearly significant
correlation between MSI and germline mutations. In 172 cases, rates of germline
and somatic mutations were 34.3% and 13.4%, respectively. The mutations of MLH1
V384D (15.7%), R217C (4.1%), and I219V (5.2%) were common in this cancer. In
addition, the yeast 2-hybrid and immunoprecipitation assays exhibited reduced
interaction between MLH1 and PMS2 in MLH1 V384D and R217C but not I219V.
Moreover, MLH1 V384D and R217C had impaired MMR activity compared with the wild
type and I219V mutation by an in vitro MMR assay. The germline mutations in MMR
genes are involved in the pathogenesis of EMPD and partially explain the genetic
abnormalities for this disease.
PMID- 27487739
TI - Mesenteric Arteriovenous Dysplasia/Vasculopathy Is Distinct From Fibromuscular
Dysplasia.
AB - Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic
vasculopathy that usually affects the carotid and renal arteries. We have
observed FMD-like vascular changes in specimens resected for ischemia or Crohn's
disease (CD). On the basis of a systematic clinicopathologic review of these 11
cases identified between 1982 and 2014, we describe a distinct mesenteric
vasculopathy that involves both arteries and veins [mesenteric arteriovenous
dysplasia/vasculopathy (MAVD/V)] and is characterized by (1) concentric/eccentric
smooth muscle collarette around the tunica media of both the artery and the vein
in >=2 foci, (2) varying degrees of intimal and medial hyperplasia and
adventitial fibrosis, and (3) lack of inflammation or thrombi. MAVD/V cases were
clinically diagnosed as CD (45%), mass/lesion (27%), ischemia (9%), obstruction
(9%), or rectal prolapse (9%). Abdominal pain for >1 year was the most common
symptom. Most patients were women (M:F=1:2.7; mean age, 63 y). Mucosal changes
mimicking CD, such as architectural distortion (55%), multifocal ulcers (73%),
and pyloric gland metaplasia (64%), were common; however, no granulomas or
transmural lymphoid aggregates were identified. Ischemic pattern of injury was
seen in 4 cases. Upon follow-up (mean, 31.2 mo), 8 patients were found to be
asymptomatic, 2 had died of unrelated causes, and 1 was lost to follow-up. We
propose the name MAVD/V for a distinct noninflammatory, nonatherosclerotic,
localized form of mesenteric vasculopathy that involves both arteries and veins,
distinct from FMD. Unlike FMD, surgical resection appears to be curative, with a
favorable clinical outcome. Awareness of this vascular entity is important as
patients may be potentially misdiagnosed as having CD and ischemic bowel disease.
PMID- 27487740
TI - Interobserver Reproducibility of Percent Gleason Pattern 4 in Prostatic
Adenocarcinoma on Prostate Biopsies.
AB - In the WHO Classification of Tumours of the Urinary System and Male Genital
Organs published in 2016, it was officially recommended that the percent of
Gleason pattern 4 (GP4) be reported on pathology reports to better reflect the
extent in Gleason score 7 tumors. In this study we assessed the reproducibility
of reporting GP4 on prostate biopsies. We analyzed prospectively 422 cores
containing GP4 from our consult cases over a period of 2.5 months. The percent
pattern 4 was assigned to all the cases in 10% increments from 0% to 100% (with
the addition of 5%) by 1 of 4 fellows in urological pathology and by the expert
urological pathologist. Out of 422 cores, 32% were an exact match and 75% were
within +/-10% (weighted kappa [kappaW] value 0.67). Cases were further stratified
on the basis of (1) scattered versus clustered GP4 in the background of Gleason
pattern 3, (2) continuous versus discontinuous tumor involvement, (3)
cribriform/glomeruloid pattern only versus poorly formed/fused pattern versus
mixed cribriform and poorly formed/fused pattern, and (4) total tumor involvement
of the core (<=10% vs. >10% of the core). No significant differences were
observed in the first 3 variables. However, in cases with <=10% involvement of
the core, 61% were within +/-10% (kappaW=0.50) compared with cases with >10%
involvement of the core, in which 78% were within +/-10% (kappaW=0.70). In
summary, we showed that assessment of percent GP4 was relatively reproducible,
with substantial agreement within +/-10% in cases. However, with <10% involvement
of the core, it was more difficult to assess in smaller foci, with only moderate
agreement. Given that in a small focus only a few glands of a given pattern can
markedly affect the percent GP4, consideration should be given to not recording
percent GP4 in small foci of Gleason score 7 tumors on needle biopsy.
PMID- 27487741
TI - Low-grade Serous Carcinoma of the Ovary: Clinicopathologic Analysis of 52
Invasive Cases and Identification of a Possible Noninvasive Intermediate Lesion.
AB - Low-grade serous carcinoma (LGSC) is an uncommon but distinct histologic subtype
of ovarian carcinoma. Although the histologic features and natural history of
LGSC have been described in the literature, there is no robust correlative study
that has specifically addressed histologic features in correlation with clinical
follow-up. To refine the criteria for invasion patterns of LGSC and determine
additional clinically pertinent morphologic features of LGSC predisposing to a
more aggressive clinical course, the clinicopathologic features of 52 LGSCs were
evaluated and compared with those of a large series of serous borderline tumors
(SBT), with and without invasive implants. To qualify for LGSC, the tumor needed
to demonstrate destructive invasion, nuclear atypia that was mild to moderate at
most (grade 1 or 2), and a mitotic index that did not exceed 12 mitoses per 10
high-power fields. On the basis of histologic evaluation, destructive invasion
was classified into 7 primary architectural patterns: (1) micropapillary and/or
complex papillary; (2) compact cell nests; (3) inverted macropapillae; (4)
cribriform; (5) glandular and/or cystic; (6) solid sheets with slit-like spaces;
and (7) single cells. Five-year overall survival and disease-free survival for
LGSC were 82% (median, 72 mo) and 47% (median, 54 mo), respectively. All the
patients with fatal outcome demonstrated tumors showing invasion with predominant
patterns of cribriform glands, micropapillae and/or complex papillae, or compact
cell nests. Notably, 2 of 9 patients with fatal outcome had only small foci of
destructive invasion (2 and 3 mm, respectively) with compact cell nests and
cribriform glands as the predominant patterns. There was no statistically
significant association between pattern of invasion and disease-free survival.
Classic stromal microinvasion, as defined by nondestructive stromal invasion <5
mm was identified in 52% of LGSC and was statistically more frequent in LGSC than
in SBT (P<0.001). In 2 LGSCs, there were areas demonstrating an intraluminal
solid proliferation of tumor cells with grade 1 or 2 nuclear atypia, which we
hypothesize may represent a noninvasive form of LGSC, as similar non-invasive
proliferations of morphologically low-grade serous carcinomatous cells were also
identified in 8 SBTs, in either solid or compact glandular/papillary formations.
One patient with this isolated noninvasive pattern in SBT developed LGSC 40
months after initial operation. LGSC was typically high stage (FIGO stages II to
IV, 86%) and bilateral (68%), with multiple foci of invasion (82%). Bilaterality
was significantly more common in high-stage disease (P=0.009). LGSC was
associated with SBT in 84% of cases, most commonly usual type (27%), followed by
cribriform (18%), micropapillary (11%), or mixed cribriform and micropapillary
(7%) types; focal micropapillary and/or cribriform features were present in an
additional 16%. The presence of intraluminal proliferations of cells resembling
LGSC occurring in SBT should prompt additional tumor sampling and assiduous
evaluation of implants (if present), as this appears to represent a form of
intraepithelial carcinoma, which may be associated with invasion elsewhere.
PMID- 27487742
TI - Correction: Tuning the Schottky contacts in the phosphorene and graphene
heterostructure by applying strain.
AB - Correction for 'Tuning the Schottky contacts in the phosphorene and graphene
heterostructure by applying strain' by Biao Liu et al., Phys. Chem. Chem. Phys.,
2016, 18, 19918-19925.
PMID- 27487743
TI - High Prevalence of Acute Exacerbation of Interstitial Lung Disease in Japanese
Patients with Systemic Sclerosis.
AB - Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by
extensive fibrosis and autoantibodies. Its clinical manifestations are diverse
and include Raynaud's phenomenon, gastrointestinal dysmotility, interstitial lung
disease (ILD), pulmonary hypertension, and renal crisis. Among these, ILD is the
primary cause of SSc-related death. It has been considered that acute
exacerbation of ILD (AE-ILD) is not common in patients with SSc; however, little
is known about the prevalence of AE-ILD in Japanese patients with SSc. In this
study, we aimed to clarify the prevalence, clinical characteristics, and
prognosis of patients with SSc who developed AE-ILD and to identify predictive
factors for AE-ILD in our Japanese cohorts. Clinical data of patients who visited
our department from 1990 to 2014 and fulfilled the 2013 classification criteria
for SSc were retrospectively reviewed. A total of 139 patients were enrolled. The
mean age of onset was 49.1 years, and 113 (81.3%) patients were female; 116
(83.5%) had limited cutaneous involvement, and the overall 10-year survival rate
was 92.0%. Among 66 (47.5%) patients with ILD, 13 (9.4%) developed AE-ILD.
Patients with AE-ILD had a significantly higher incidence of overlap with
polymyositis (PM) or dermatomyositis (DM) and lower prevalence of anticentromere
antibodies with higher mortality rate compared with those without AE-ILD.
Multivariate Cox regression analysis identified that an overlap with PM or DM was
the most significant predictive factor for AE-ILD. Our study results suggest that
Japanese patients with SSc, particularly patients overlapped with PM or DM, have
a high risk of AE-ILD.
PMID- 27487744
TI - Impact of clinical training on supra-aortic duplex and transcranial doppler
examination concordance.
AB - Sonographic tests are observer-dependent. With 1,527 consecutive patients, 22
trainees were assessed at baseline and after a hands-on 1:1 program, with a pre
examination median of 76 studies/trainee. We evaluated the required number of
supervised examinations to reach a 0.80 kappa index (ki). Statistics included
linear and exponential generalized estimating equation models. In the exponential
model, 76 studies for carotid-duplex and >102 for vertebral-duplex and
transcranial Doppler were needed for a 0.80 ki. "Relevant-categories" after
training ki was 0.80 in carotid-duplex and transcranial Doppler but 0.60 in
vertebral-duplex. A fixed training does not guarantee a high ki. Measuring the
acquired skills of every trainee would improve quality. (c) 2016 Wiley
Periodicals, Inc. J Clin Ultrasound 44:571-579, 2016.
PMID- 27487745
TI - Structural insights into cardiolipin transfer from the Inner membrane to the
outer membrane by PbgA in Gram-negative bacteria.
AB - The outer membrane (OM) of Gram-negative bacteria is a unique asymmetric lipid
bilayer in which the outer leaflet is composed of lipopolysaccharide (LPS) and
the inner leaflet is formed by glycerophospholipid (GPL). The OM plays a
fundamental role in protecting Gram-negative bacteria from harsh environments and
toxic compounds. The transport and assembly pathways for phospholipids of
bacterial OM are unknown. Cardiolipin (CL) plays an important role in OM
biogenesis and pathogenesis, and the inner membrane (IM) protein PbgA, containing
five transmembrane domains and a globular domain in periplasm has been recently
identified as a CL transporter from the IM to the OM with an unknown mechanism.
Here we present the first two crystal structures of soluble periplasmic globular
domain of PbgA from S. typhimurium and E. coli, which revealed that the globular
domains of PbgA resemble the structures of the arylsulfatase protein family and
contains a novel core hydrophobic pocket that may be responsible for binding and
transporting CLs. Our structural and functional studies shed an important light
on the mechanism of CL transport in Gram-negative bacteria from the IM to the OM,
which offers great potential for the development of novel antibiotics against
multi-drug resistant bacterial infections.
PMID- 27487747
TI - Direct reprogramming to multipotent trophoblast stem cells, and is pluripotency
needed for regenerative medicine either?
PMID- 27487746
TI - Strength Training Prevents Hyperinsulinemia, Insulin Resistance, and Inflammation
Independent of Weight Loss in Fructose-Fed Animals.
AB - The aim of this study was to compare the effects of aerobic, strength, and
combined training on metabolic disorders induced by a fructose-rich diet. Wistar
rats (120 days old) were randomized into five groups (n = 8-14): C (control diet
and sedentary), F (fed the fructose-rich diet and sedentary), FA (fed the
fructose-rich diet and subject to aerobic exercise), FS (fed the fructose-rich
diet and subject to strength exercise), and FAS (fed the fructose-rich diet and
subject to combined aerobic and strength exercises). After the 8-week experiment,
glucose homeostasis, blood biochemistry, tissue triglycerides, and inflammation
were evaluated and analyzed. The strength protocol exerted greater effects on
glucose homeostasis, insulin sensitivity, and liver lipid contents than other
protocols (all P < 0.05). All three exercise protocols induced a remarkable
reduction in inflammation, tissue triglyceride content, and inflammatory
pathways, which was achieved through c-Jun NH2-terminal kinase (JNK)
phosphorylation and factor nuclear kappa B (NFkB) activation in both the liver
and the muscle. Our data suggest that strength training reduced the severity of
most of the metabolic disorders induced by a fructose-rich diet and could be the
most effective strategy to prevent or treat fructose-induced metabolic diseases.
PMID- 27487749
TI - Attending a Professional Conference.
PMID- 27487748
TI - Inherited dysfunctional platelet P2Y12 receptor mutations associated with
bleeding disorders.
AB - The platelet adenosine 5'-diphosphate (ADP) receptor P2Y12 (P2Y12R) plays a
critical role in platelet aggregation. The present report illustrates an update
of dysfunctional platelet P2Y12R mutations diagnosed with congenital lifelong
bleeding problems. Described patients with heterozygous or homozygous
substitution in the P2Y12R gene and qualitative abnormalities of the platelet
P2Y12R are summarized. Recently, a further dysfunctional variant of P2Y12R has
been identified in two brothers who presented with a lifelong severe bleeding
disorder. During in vitro aggregation studies, the patient's platelets show a
markedly reduced and rapid reversible ADP-promoted aggregation. A homozygous
c.561T>A substitution that changes the codon for His187 to Gln (p.His187Gln) in
the P2Y12R gene has been identified. This mutation causes no change in receptor
expression but decreases the affinity of the ligand for the receptor, even at
high concentrations. Structure modelling studies indicated that the p.His187Gln
mutation, located in the fifth transmembrane spanning domain (TM5), impairs
conformational changes of the receptor. Structural integrity of the TM5 region is
necessary for agonist and antagonist binding and for correct receptor function.
PMID- 27487750
TI - The Certified Clinical Nurse Leader in Critical Care.
AB - Challenges of the current health system in the United States call for
collaboration of health care professionals, careful utilization of resources, and
greater efficiency of system processes. Innovations to the delivery of care
include the introduction of the clinical nurse leader role to provide leadership
at the point of care, where it is needed most. Clinical nurse leaders have
demonstrated their ability to address needed changes and implement improvements
in processes that impact the efficiency and quality of patient care across the
continuum and in a variety of settings, including critical care. This article
describes the role of the certified clinical nurse leader, their education and
skill set, and outlines outcomes that have been realized by their efforts.
Specific examples of how clinical nurse leaders impact critical care nursing are
discussed.
PMID- 27487751
TI - Cardiac Radiofrequency Ablation: A Clinical Update for Nurses.
AB - The field of electrophysiology (EP) has rapidly evolved from a focus on
diagnostic procedures to an emphasis on interventions. Many cardiac arrhythmias
traditionally treated with antiarrhythmic agents, cardioversion, or cardiac
surgery are now routinely cured with cardiac ablation. To optimally manage the
care of cardiac ablation patients, it is essential that nurses have an
understanding of the EP procedures and related nursing implications. There are
extensive evidence-based resources available in the medical literature; however,
there are limited publications geared toward nurses caring for cardiac ablation
patients.This article provides an overview of EP diagnostic and cardiac radio
frequency ablation procedures for select atrial and ventricular tachyarrhythmias.
Evidence-based nursing practices related to postprocedure care will be addressed.
The objective of this article is to increase nurses' knowledge of common cardiac
ablation procedures and the nursing management of the patient postprocedure.
PMID- 27487752
TI - Implementation of a Nurse-Led Family Meeting in a Neuroscience Intensive Care
Unit.
AB - PURPOSE/OBJECTIVES: The aims of this study were to develop, implement, and
evaluate the impact of early intensive care unit (ICU) nurse-led family meetings
on nurse-family communication, family decision making, and satisfaction of family
members. BACKGROUND: Intensive care unit nurses are in an ideal position to meet
family needs, and family members may cope better with the crisis of an ICU
admission if consistent honest information is provided by nurses; however, there
are no early ICU family meetings led by bedside nurses. METHODS: This quality
improvement project was implemented in a 10-bed neuroscience ICU over a 3-month
period. A convenience sample of 23 nurses participated in the project. Following
development of a communication protocol to facilitate nurse-led meetings, the
nurses received education and then implemented the protocol. Thirty-one family
members participated in the project. Family members were surveyed before and
after the meetings. RESULTS: Mean meeting time was 26 (SD, 14) minutes. Following
implementation of the meetings, findings demonstrated that families felt that
communication improved (P = .02 and P = .008), they had appropriate information
for decision making allowing them to feel in control (P = .002), and there was an
increase in family satisfaction (P = .001). CONCLUSION: Early ICU nurse-led
family meetings were feasible, improved communication between ICU nurses and
family members, facilitated decision making in ICU families, and increased
satisfaction of family members.
PMID- 27487753
TI - Evaluation of a Progressive Mobility Protocol in Postoperative Cardiothoracic
Surgical Patients.
AB - Cardiothoracic surgical patients are at high risk for complications related to
immobility, such as increased intensive care and hospital length of stay,
intensive care unit readmission, pressure ulcer development, and deep vein
thrombosis/pulmonary embolus. A progressive mobility protocol was started in the
thoracic cardiovascular intensive care unit in a rural academic medical center.
The purpose of the progressive mobility protocol was to increase mobilization of
postoperative patients and decrease complications related to immobility in this
unique patient population. A matched-pairs design was used to compare a randomly
selected sample of the preintervention group (n = 30) to a matched
postintervention group (n = 30). The analysis compared outcomes including
intensive care unit and hospital length of stay, intensive care unit readmission
occurrence, pressure ulcer prevalence, and deep vein thrombosis/pulmonary
embolism prevalence between the 2 groups. Although this comparison does not
achieve statistical significance (P < .05) for any of the outcomes measured, it
does show clinical significance in a reduction in hospital length of stay,
intensive care unit days, in intensive care unit readmission rate, and a decline
in pressure ulcer prevalence, which is the overall goal of progressive mobility.
This study has implications for nursing, hospital administration, and therapy
services with regard to staffing and cost savings related to fewer complications
of immobility. Future studies with a larger sample size and other populations are
warranted.
PMID- 27487754
TI - An Association Between Pain and American Association of Respiratory Care 2010
Guidelines During Tracheal Suctioning.
AB - INTRODUCTION: Tracheal suctioning is recalled by mechanically ventilated patients
as the most painful procedure during their stay in the intensive care unit. AIM:
The aim of this study was to evaluate whether the implementation of American
Association of Respiratory Care suction guidelines positively affects the levels
of patients' pain. MATERIALS AND METHODS: This is a prospective observational
study on adult patients admitted to 2 general intensive care units. Pain levels
in sedated mechanically ventilated patients were recorded before, during, and
after tracheal suctioning, using the Critical Care Pain Observation Tool (CPOT).
RESULTS: Forty-seven patients were enrolled, with a mean age of 61.72 (+/-18.46)
years. Median CPOT value was 0 (quartile 1 [Q1] [25%], 0; quartile 3 [Q3] [75%],
0; min, 0; max, 2) during the procedure. The Critical Care Pain Observation Tool
reached a median value of 3, while 5 minutes after suctioning. Postprocedural
CPOT median score was 0 (Q1 [25%], 0; Q3 [75%], 0; min, 0; max, 2). The median
number of passes during suctioning was 1 (Q1, 1; Q3, 2). The sizes of suction
catheters used in the recorded procedures were as follows: 12F in 27 cases (57%),
14F in 18 cases (38%), and 10F in 2 cases (5%). The median size of the
endotracheal tube was 7.5 mm (Q1, 7.5; Q3, 8). The correct ratio between
endotracheal tube diameter and suction catheter was used in 24 procedures (51%).
CONCLUSIONS: Despite the low number of patients, this study showed that the
implementation of the American Association of Respiratory Care 2010 endotracheal
suctioning guidelines into practice helps to reduce procedural-induced pain.
Therefore, training and continuing education are important for clinical staff
performing tracheal suctioning.
PMID- 27487758
TI - A Closing Word.
PMID- 27487756
TI - A Pilot Study Implementing a Protocol Using Dexmedetomidine as a Safe Alternative
to Traditional Sedation to Decrease Ventilator Days for Patients Difficult to
Extubate.
AB - BACKGROUND: Traditional sedation for mechanically ventilated patients causes
delirium, which increases the patients' length of stay while hospitalized. When
extubation is attempted, these medications must be discontinued because of the
side effect of respiratory depression, leaving patients anxious and agitated,
delaying extubation and prolonging the need for mechanical ventilation.
Dexmedetomidine is a safe alternative sedative that does not cause delirium or
respiratory depression. During the weaning process, dexmedetomidine can be
continued, allowing the patient to remain calm and successfully extubated.
OBJECTIVES: The aim of this study is to decrease the length of stay for
mechanically ventilated patients by implementing a dexmedetomidine protocol for
difficult-to-extubate patients during the weaning process. METHODS: A
preintervention/postintervention design pilot study was done comparing the
patient mean of length of stay on mechanical ventilation. A Mann-Whitney U test
was used because of the small sample size. RESULTS: Over the 3-month
implementation period, 15 patients received dexmedetomidine. None of the patients
experienced adverse reactions while on dexmedetomidine. There was a trend of
decreasing mechanical ventilation length of stay but no significant difference
was noted between the preimplementation and postimplementation groups.
CONCLUSION: Dexmedetomidine was a safe alternative to traditional sedation for
difficult-to-extubate patients when a bolus dose was not given.
PMID- 27487759
TI - Do Not Forget the Clinical Nurse Leader.
PMID- 27487760
TI - Response to Letter to Editor.
PMID- 27487761
TI - Morbidity and medication consumption among users of home telecare services.
AB - Telecare is a healthcare resource based on new technologies that, through the
services offered, attempt to help elderly people to continue living in their
homes. In this sense, first-generation telecare services have quickly developed
in Europe. The aim of this work was to define the profile, pattern of medication
consumption and disease frequencies of elderly users of a telecare service. The
cross-sectional study involved 742 Spanish community-dwelling elders (85.3% of
the total users aged 65 years and over who used a telecare service before the end
of the data collection period). Data were collected between March and September
2012. Subjects' mean age was 83.3 (SD 6.6) years, and the majority lived alone
(78.3%) and were female (85.8%). The mean Charlson comorbidity index score was
1.13 (SD 1.1), and the mean number of prescribed medications per day was 5.6 (SD
3.0). The most frequent diseases were hypertension (51.1%) and rheumatic
disorders (44%); and the most consumed medications were those for the
cardiovascular (75%) and nervous (65.2%) systems. For the total sample, the three
main determinants of polymedication (five or more medications) were hypertension,
anxiety-depressive symptoms and coronary heart disease. Regardless of the social
elements contributing to the implementation of telecare services, specific health
characteristics of potential users, such as morbidity and polypharmacy, should be
carefully considered when implementing telecare services in the coming years.
PMID- 27487762
TI - Cultural influences on suicide in Japan.
AB - Following the economic crash of the late 1990s, the suicide rate in Japan
increased to a rate of over 30 000 people per year and has been one of the
highest in the world. Cultural factors have influenced this high suicide rate,
such as a tradition of honorable suicide as well as permissive attitudes towards
suicide that remain in modern times. Additionally, the economic downturn,
particularly the trend of unemployment in middle-aged men, also played a
significant role in the high suicide rate. The suicide rate has started to
decrease in recent years perhaps in part due to suicide prevention measures
undertaken by the government.
PMID- 27487763
TI - Transcatheter aortic valve repair for management of aortic insufficiency in
patients supported with left ventricular assist devices.
AB - The development of new aortic insufficiency after a period of support with a left
ventricular assist device can result in progressive heart failure symptoms.
Transcatheter aortic valve repair can be an effective treatment in selected
patients, but the lack of aortic valve calcification can result in unstable
prostheses or paravalvular leak. We describe a technique of deploying a self
expanding CoreValve (Medtronic, Minneapolis, MN, USA) into the aortic annulus,
followed by a balloon-expandable SAPIEN-3 (Edwards, Irvine, CA, USA).
PMID- 27487765
TI - New Volleyballenes: Y20C60 and La20C60.
AB - Two new stable Volleyballenes, the Y20C60 and La20C60 molecular clusters, are
proposed on the basis of first-principles density functional theory. In
conjunction with recent findings for the scandium system, these findings
establish Volleyballene M20C60 molecules as a general class of stable molecules
within the fullerene family. Both Y20C60 and La20C60 molecules have Th point
group symmetries and relatively large HOMO-LUMO gaps.
PMID- 27487764
TI - Combined effects of cadmium and salinity on juvenile Takifugu obscurus: cadmium
moderates salinity tolerance; salinity decreases the toxicity of cadmium.
AB - Obscure puffer Takifugu obscurus, a species of anadromous fish, experiences
several salinity changes in its lifetime. Cadmium (Cd) is a toxic heavy metal
that can potentially induce oxidative stress in fish. The present study aimed to
detect the combined effects of Cd (0, 5, 10, 20 and 50 mg L(-1)) and salinity (0,
15 and 30 ppt) on juvenile T. obscurus. Results showed the juveniles could
survive well under different salinities; however, with Cd exposure, the survival
rates significantly decreased at 0 and 30 ppt. At 15 ppt, tolerance to Cd
increased. Cd exposure clearly induced oxidative stress, and the responses among
different tissues were qualitatively similar. Salinity acted as a protective
factor which could reduce the reactive oxygen species and malondialdehyde levels.
In addition, salinity could enhance the antioxidant defense system, including
superoxide dismutase, catalase and glutathione. Na(+)/K(+)-ATPase activity
significantly decreased under Cd exposure in gill, kidney and intestine. These
findings indicated that Cd could moderate the adaptability of juvenile T.
obscurus to high salinity and low salinity played a protective role upon Cd
exposure. Thus, the role of salinity should be considered when evaluating the
effect of heavy metals on anadromous and estuarine fishes.
PMID- 27487766
TI - Astroglial NF-kB contributes to white matter damage and cognitive impairment in a
mouse model of vascular dementia.
AB - Vascular cognitive impairment is the second most common form of dementia. The
pathogenic pathways leading to vascular cognitive impairment remain unclear but
clinical and experimental data have shown that chronic reactive astrogliosis
occurs within white matter lesions, indicating that a sustained pro-inflammatory
environment affecting the white matter may contribute towards disease
progression. To model vascular cognitive impairment, we induced prolonged mild
cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This
chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia
within white matter tracts, demyelination and axonal degeneration, consecutive
spatial memory deficits, and loss of white matter integrity, as measured by ultra
high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis
was accompanied by activation of the pro-inflammatory transcription factor
nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant
negative inhibitor of NF-kB under the control of the astrocyte-specific glial
fibrillary acid protein (GFAP) promoter (GFAP-IkBalpha-dn), we found that
transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and
axonal loss, maintained white matter structural integrity, and preserved memory
function. Collectively, our results imply that pro-inflammatory changes in white
matter astrocytes may represent an important detrimental component in the
pathogenesis of vascular cognitive impairment, and that targeting these pathways
may lead to novel therapeutic strategies.
PMID- 27487767
TI - The global threat of Zika virus to pregnancy: epidemiology, clinical
perspectives, mechanisms, and impact.
AB - Zika virus (ZIKV) is a mosquito-borne flavivirus that has newly emerged as a
significant global threat, especially to pregnancy. Recent major outbreaks in the
Pacific and in Central and South America have been associated with an increased
incidence of microcephaly and other abnormalities of the central nervous system
in neonates. The causal link between ZIKV infection during pregnancy and
microcephaly is now strongly supported. Over 2 billion people live in regions
conducive to ZIKV transmission, with ~4 million infections in the Americas
predicted for 2016. Given the scale of the current pandemic and the serious and
long-term consequences of infection during pregnancy, the impact of ZIKV on
health services and affected communities could be enormous. This further
highlights the need for a rapid global public health and research response to
ZIKV to limit and prevent its impact through the development of therapeutics,
vaccines, and improved diagnostics. Here we review the epidemiology of ZIKV; the
threat to pregnancy; the clinical consequences and broader impact of ZIKV
infections; and the virus biology underpinning new interventions, diagnostics,
and insights into the mechanisms of disease.
PMID- 27487768
TI - The occurrence of spoilage yeasts in cream-filled bakery products.
AB - BACKGROUND: Filling creams can provide an adequate substrate for spoilage yeasts
because some yeasts can tolerate the high osmotic stress in these products. To
discover the source of spoilage of a cream-filled baked product, end products,
raw materials, indoor air and work surfaces were subjected to microbiological and
molecular analyses. The efficacy of disinfectants against spoilage yeasts was
also assessed. RESULTS: The analyses on end products revealed the presence of the
closest relatives to Zygosaccharomyces bailii with counts ranging from 1.40 to
4.72 log cfu g-1 . No spoilage yeasts were found in the indoor air and work
surfaces. Polymerase chain reaction-denaturing gradient gel electrophoresis
analysis, carried out directly on filling creams collected from unopened cans,
showed the presence of bands ascribed to the closest relatives to Z. bailii sensu
lato, although with counts < 1 log cfu g-1 . Susceptibility testing of yeast
isolates to disinfectants showed a significantly lower effect of 10% alkyl
dimethyl benzyl ammonium chloride. Different responses of isolates to the tested
disinfectants were seen. CONCLUSION: To guarantee the quality of end products,
reliable and sensitive methods must be used. Moreover, hygiene and the
application of good manufacturing practices represent the most efficient way for
the prevention and minimization of cross-contamination. (c) 2016 Society of
Chemical Industry.
PMID- 27487769
TI - Population genetic processes affecting the mode of selective sweeps and effective
population size in influenza virus H3N2.
AB - BACKGROUND: Human influenza virus A/H3N2 undergoes rapid adaptive evolution in
response to host immunity. Positively selected amino acid substitutions have been
detected mainly in the hemagglutinin (HA) segment. The genealogical tree of HA
sequences sampled over several decades comprises a long trunk and short side
branches, which indicates small effective population size. Various studies have
reproduced this unique genealogical structure by modeling recurrent positive
selection. However, it has not been clearly demonstrated whether recurrent
selective sweeps alone can explain the limited level of genetic diversity
observed in the HA of H3N2. In addition, the variation-reducing impacts of other
evolutionary processes - background selection and complex demography - relative
to that of positive selection have never been explicitly evaluated. RESULTS: In
this paper, using computer simulation of a viral population evolving under
recurrent selective sweeps we demonstrate that positive selection alone, if it
occurs at a rate estimated by previous studies, cannot lead to such a small
effective population size. Genetic hitchhiking fails to completely wipe out pre
existing variation because soft, rather than hard, selective sweeps prevail under
realistic parameters of mutation rate and population size. We find that antigenic
cluster-transition substitutions in HA occur as hard sweeps. This indicates that
the effective population size under which those mutations arise must be much
smaller than the actual population size due to other evolutionary forces before
selective sweeps further reduce it. We thus examine the effects of background
selection and metapopulation dynamics in reducing the effective population size,
using parameter values that reproduce other aspects of molecular evolution in
H3N2. When either process is incorporated in recurrent selective sweep
simulation, selective sweeps are mostly hard and the observed level of synonymous
diversity is obtained with large census population size. CONCLUSIONS: Background
selection and metapopulation dynamics have greater variation reducing power than
recurrent positive selection under realistic parameters in H3N2. Therefore, these
evolutionary processes are likely to play crucial roles in reducing the effective
population size of H3N2 viruses and thus explaining the characteristic shape of
H3N2 genealogy.
PMID- 27487770
TI - Community-based pediatric palliative care for health related quality of life,
hospital utilization and costs lessons learned from a pilot study.
AB - BACKGROUND: Children with chronic complex-medical conditions comprise a small
minority of children who require substantial healthcare with major implications
for hospital utilization and costs in pediatrics. Community-Based Pediatric
Palliative Care (CBPPC) provides a holistic approach to patient care that can
improve their quality of life and lead to reduced costs of hospital care. This
study's purpose was to analyze and report unpublished evaluation study results
from 2007 that demonstrate the potential for CBPPC on Health Related Quality of
Life (HRQoL) and hospital utilization and costs in light of the increasing
national focus on the care of children with complex-medical conditions, including
the Affordable Care Act's emphasis on patient-centered outcomes. METHODS: A multi
method research design used primary data collected from caregivers to determine
the Program's potential impact on HRQoL, and administrative data to assess the
Program's potential impact on hospital utilization and costs. Caregivers (n=53)
of children enrolled in the Northeast Florida CBPPC program (Community PedsCare)
through the years 2002-2007 were recruited for the Health Related Quality of Life
(HRQoL) study. Children (n=48) enrolled in the Program through years 2000-2006
were included in the utilization and cost study. RESULTS: HRQoL was generally
high, and hospital charges per child declined by $1203 for total hospital
services (p=.34) and $1047 for diagnostic charges per quarter (p=0.13). Hospital
length of stay decreased from 2.92 days per quarter to 1.22 days per quarter
(p<.05). CONCLUSION: The decrease in hospital utilization and costs and the high
HRQoL results indicate that CBPPC has the potential to influence important
outcomes for the quality of care available for children with complex-medical
conditions and their caregivers.
PMID- 27487771
TI - Immunoregulatory soluble CTLA-4 modifies effector T-cell responses in systemic
lupus erythematosus.
AB - BACKGROUND: The inhibitory CTLA-4 molecule is a crucial regulator of immune
responses and a target for therapeutic intervention in both autoimmunity and
cancer. In particular, CTLA-4 is important in controlling antigen-specific
immunity, including responses to autoantigens associated with autoimmune disease.
Here, we investigate cytokine responses to a range of lupus-associated
autoantigens and assess whether the alternatively spliced isoform of CTLA-4,
soluble CTLA-4 (sCTLA-4), contributes to immune regulation of autoantigen
specific immunity in systemic lupus erythematosus (SLE). METHODS: The cell
culture supernatant production of sCTLA-4 as well as the cytokines IL-10, IFN
gamma, and IL-17 from peripheral blood mononuclear cells (PBMC) from lupus
patients and age- and sex-matched healthy volunteer donors were measured in
response to previously identified histone and small nuclear ribonucleoprotein
(snRNP) autoantigen-derived peptides (H391-105, H471-93, and U170K131-151) by
ELISA. We also examined the functional contribution of sCTLA-4 to immune
regulation in the context of these autoantigenic peptides following blockade of
sCTLA-4 with a selective anti-sCTLA-4 monoclonal antibody, JMW-3B3. RESULTS: We
identified responses to autoantigenic peptides, which revealed qualitative
differences in cytokine (IL-10, IL-17, and IFN-gamma) profiles between SLE
patients and healthy donors. PBMC from healthy donors responded to each of the
lupus peptides by secreting IFN-gamma and IL-17, but PBMC from SLE patients
produced IL-10. Although we did not observe differences in the levels of serum or
PBMC culture supernatant sCTLA-4 in either cohort, blockade of sCTLA-4 in PBMC
cultures responding to antigen enhanced the cytokine profiles associated with
each group. CONCLUSION: The results show that lupus autoantigen-derived peptides
display varied immunogenicity in lupus versus healthy volunteer donors, while
sCTLA-4 acts to regulate the T-cell activity independently of response profile.
PMID- 27487774
TI - Dyella humi sp. nov., isolated from forest soil.
AB - A Gram-stain-negative, aerobic, motile, rod-shaped, yellow-pigmented bacterium,
designated as DHG40T, was isolated from a soil sample collected from the forest
of Dinghushan Biosphere Reserve, Guangdong Province, China. Strain DHG40T grew at
pH 4.0-8.0 and 10-37 degrees C (optimum at pH 6.0-7.0 and 25-28 degrees C).
NaCl inhibited growth at concentrations above 2.5 % (w/v). Phylogenetic analysis
based on 16S rRNA gene sequences revealed that the isolate fell within the
cluster of the genus Dyella. Strain DHG40T was closely related to Dyella
ginsengisoli Gsoil 3046T (97.6 % 16S rRNA gene sequence similarity), Dyella
marensis CS5-B2T (97.5 %), Dyella koreensis BB4T (97.4 %) and Dyella jejuensis
JP1T (97.4 %). The DNA-DNA relatedness values between strain DHG40T and its
phylogenetically closest relatives were all below 40 %. The DNA G+C content was
60.3 mol%. In addition, iso-C15 : 0, iso-C16 : 0, iso-C17 : 0 and iso-C17 :
1omega9c were the major fatty acids (>10 %) and ubiquinone-8 was the respiratory
quinone. The major polar lipids were phosphatidylethanolamine,
phosphatidylmethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, an
unidentified aminolipid and an unidentified phospholipid. On the basis of
phylogenetic, phenotypic, physiological and chemotaxonomic distinctiveness,
strain DHG40T should be placed in the genus Dyella as a representative of a novel
species, for which the name Dyella humi sp. nov. is proposed. The type strain is
DHG40T (=KCTC 42629T=LMG 28842T).
PMID- 27487773
TI - Pathogenesis of Korean SapelovirusA in piglets and chicks.
AB - Sapelovirus A (SV-A), formerly known as porcine sapelovirus as a member of a new
genus Sapelovirus, is known to cause enteritis, pneumonia, polioencephalomyelitis
and reproductive disorders in pigs. We have recently identified alpha2,3-linked
sialic acid on GD1a ganglioside as a functional SV-A receptor rich in the cells
of pigs and chickens. However, the role of GD1a in viral pathogenesis remains
elusive. Here, we demonstrated that a Korean SV-A strain could induce diarrhoea
and intestinal pathology in piglets but not in chicks. Moreover, this Korean SV-A
strain had mild extra-intestinal tropisms appearing as mild, non-suppurative
myelitis, encephalitis and pneumonia in piglets, but not in chicks. By real-time
reverse transcription (RT) PCR, higher viral RNA levels were detected in faecal
samples than in sera or extra-intestinal organs from virus-inoculated piglets.
Immunohistochemistry confirmed that high viral antigens were detected in the
epithelial cells of intestines from virus-inoculated piglets but not from chicks.
This Korean SV-A strain could bind the cultured cell lines originated from
various species, but replication occurred only in cells of porcine origin. These
data indicated that this Korean SV-A strain could replicate and induce pathology
in piglets but not in chicks, suggesting that additional porcine-specific factors
are required for virus entry and replication. In addition, this Korean SV-A
strain is enteropathogenic, but could spread to the bloodstream from the gut and
disseminate to extra-intestinal organs and tissues. These results will contribute
to our understanding of SV-A pathogenesis so that efficient anti-sapelovirus
drugs and vaccines could be developed in the future.
PMID- 27487772
TI - IABP: history-evolution-pathophysiology-indications: what we need to know.
AB - Treatment with the intraaortic balloon pump (IABP) is the most common form of
mechanical support for the failing heart. Augmentation of diastolic pressure
during balloon inflation contributes to the coronary circulation and the
presystolic deflation of the balloon reduces the resistance to systolic output.
Consequently, the myocardial work is reduced. The overall effect of the IABP
therapy is an increase in the myocardial oxygen supply/demand ratio and thus in
endocardial viability.This is an overall synopsis of what we need to know
regarding IABP. Furthermore, this review article attempts to systematically
delineate the pathophysiology linked with the hemodynamic consequences of IABP
therapy. The authors also look at the future of the use of the balloon pump and
conclude that the positive multi-systemic hemodynamic regulation during IABP
treatment should further justify its use.
PMID- 27487775
TI - Characteristics and outcomes of women initiating ART during pregnancy versus
breastfeeding in Option B+ in Malawi.
AB - BACKGROUND: Malawi adopted the PMTCT strategy 'Option B+' in 2011, providing life
long ART for all HIV-infected pregnant and breastfeeding women. We explored
differences in characteristics and outcomes of women initiating ART during
pregnancy versus breastfeeding. METHODS: We conducted a retrospective cohort
analysis of women in Zomba District, southern Malawi, from January 2012-
September 2013. Data were extracted from the Zomba District Observational Cohort
Study, a surveillance project collecting data from standardized Ministry of
Health ART monitoring tools. RESULTS: 1986 (67.2 %) women initiated ART during
pregnancy and 969 (32.8 %) during breastfeeding. Women initiating ART in
breastfeeding were more likely to be > 30 years (aOR = 1.33, 95 % CI1.11-1.59, p
= 0.003) and have WHO Stage 3/4 (aOR = 2.74, 95 % CI1.94-3.87, p < 0.001).
Eighteen (0.6 %) deaths occurred and 942 (31.9 %) women defaulted ART. 'Early'
death (< 30 days) occurred in 3 (0.1 %) women and 449 (16.4 %) women defaulted
early. Death/default < 30 days was more likely among women initiating ART during
pregnancy (aOR 1.62, 95 % CI1.28-2.05, p < 0.001) or < 30 years old (aOR 1.27, 95
% CI 1.02-1.57, p = 0.03) and was less likely among those with WHO Stage 3/4 (aOR
0.30, 95 % CI 0.15-0.60, p < 0.001). Using Kaplan-Meier estimators to investigate
time to death/default, we showed a sharp drop in death/default-free survival
probability at time zero, yet survival probability decreased in a nearly linear
manner after this initial period of high default. Women under 30 years had
increased rates of death/default over time (log rank test: p < 0.001), however no
significant differences were observed in death/default over time associated with
timing of ART initiation, documented clinical stage at initiation, health clinic
size or adherence rates. CONCLUSIONS: Many women in Malawi started ART during
breastfeeding within Option B+ and were older and had more advanced WHO Clinical
Staging. This represents a missed PMTCT opportunity to initiate treatment early
in pregnancy. Early defaulting is identified as a challenge within Option B+, and
was more likely among younger women and those initiating ART in pregnancy.
Targeted research to understand factors associated with uptake of ART during
pregnancy and retention in care could improve the efficacy of Option B+ in
Malawi.
PMID- 27487777
TI - Hepatic hydatid disease complications: review of imaging findings and clinical
implications.
AB - Hydatid disease is a zoonotic parasitic disease. The liver is the most commonly
affected organ, and hepatic hydatid disease complications are not uncommon.
Hydatid cyst superinfection, intrabiliary rupture, and direct rupture into the
thoracic or abdominal cavities are the frequently encountered complications.
Other exceedingly rare complications include rupture of the cyst into hollow
viscera, abdominal wall invasion, and hepatic vasculature-related complications
such as portal vein thrombosis and Budd-Chiari syndrome. These complications have
variable clinical presentations and imaging findings and require different
medical and surgical managements. We aim to provide a spectrum of imaging
findings of different common and uncommon complications of hepatic hydatid
disease with emphasis on their clinical implications.
PMID- 27487776
TI - Application of a simplified definition of diastolic function in severe sepsis and
septic shock.
AB - BACKGROUND: Left ventricular diastolic dysfunction is common in patients with
severe sepsis or septic shock, but the best approach to categorization is
unknown. We assessed the association of common measures of diastolic function
with clinical outcomes and tested the utility of a simplified definition of
diastolic dysfunction against the American Society of Echocardiography (ASE) 2009
definition. METHODS: In this prospective observational study, patients with
severe sepsis or septic shock underwent transthoracic echocardiography within 24
h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of
diastolic function and used random forest analysis to assess their association
with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby
suggest a simplified definition. We then compared patients categorized by the ASE
2009 definition and our simplified definition. RESULTS: We studied 167 patients.
The ASE 2009 definition categorized only 35 % of patients. Random forest analysis
demonstrated that the left atrial volume index and deceleration time, central to
the ASE 2009 definition, were not associated with clinical outcomes. Our
simplified definition used only e' and E/e', omitting the other measurements. The
simplified definition categorized 87 % of patients. Patients categorized by
either ASE 2009 or our novel definition had similar clinical outcomes. In both
definitions, worsened diastolic function was associated with increased prevalence
of ischemic heart disease, diabetes, and hypertension. CONCLUSIONS: A novel,
simplified definition of diastolic dysfunction categorized more patients with
sepsis than ASE 2009 definition. Patients categorized according to the simplified
definition did not differ from patients categorized according to the ASE 2009
definition in respect to clinical outcome or comorbidities.
PMID- 27487778
TI - Identification and characterization of novel anticoagulant peptide with
thrombolytic effect and nutrient oligopeptides with high branched chain amino
acid from Whitmania pigra protein.
AB - Natural and nutrient substances for cardiovascular disease are promising and
capture researchers' minds. Two kinds of novel bioactive peptides (high Fischer's
ratio oligopeptides and anticoagulant peptides) were obtained from Whitmania
pigra protein via enzymatic hydrolysis. An oligopeptide (MW<874.0 Da) named as
HF2 was obtained via chromatography purification procedures with a high Fischer's
ratio of 31.92 +/- 1.36 and low phenylalanine + tyrosine content of 0.98 +/- 0.04
%. Another peptide (WA3-1), prepared by alcalase AF 2.4 L-catalyzed hydrolysis
and then purified by DEAE Sepharose FF, gel Sephadex G-15 chromatography,
exhibited high anticoagulant activity with prolonging significantly plasma
clotting time on activated partial thromboplastin time, prothrombin time,
thrombin time (p < 0.01) and powerful thrombolytic activity. Amino acid
composition and MALDI-TOF/TOF MS analysis showed that WA3-1 contained 11 amino
acids (MW: 1422.0 Da) with the sequence as NH2-His-Asp-Phe-Leu-Asn-Asn-Lys-Leu
Glu-Tyr-Glu-COOH. Abundant negatively charged amino acids in C-terminal, as well
as the special residue Lys contribute to its anticoagulant capacity. This
research provided a novel natural candidate for the manufacture of nutrient
oligopeptides with high branched chain amino acid, and anticoagulant thrombolytic
agent in pharmaceutical industry with helping prevent from thrombosis and related
cardiovascular diseases.
PMID- 27487779
TI - Primary pulmonary plasmacytoma: a case report introduction.
AB - BACKGROUND: Extramedullary plasmacytoma is a rare plasma cell neoplasm within
soft tissue and without bone marrow involvement or other systemic characteristics
of multiple myeloma. Primary pulmonary plasmacytoma is a rare type of
extramedullary plasmacytoma. CASE PRESENTATION: A 48-year-old male with a tumor
in the right middle ear was referred to our hospital. A routine chest X-ray was
arranged and showed enlargement of the left lung hilum. His bilateral breathing
sounded clear. A chest CT scan revealed a well-circumscribed mass. Pathological
biopsy yielded a diagnosis of isolated pulmonary plasmacytoma. CONCLUSIONS: This
is the first presentation of primary pulmonary plasmacytoma with a solitary
pulmonary nodule and no lymph node involvement.
PMID- 27487780
TI - Outcomes from an orientation model to reduce attrition in paediatric weight
management.
AB - We aimed to reduce attrition of newly referred patients in a paediatric weight
management programme by implementing an orientation to address families'
expectations and screen for and support behavioural and mental health problems
and psychosocial stressors at programme outset. Orientation impact was monitored
with run charts with percentages of scheduled encounters completed. Long-term
impact was assessed by comparing patients in the initial 6 months of the
orientation to a baseline group of referred patients during the same 6-month time
interval in the prior year (Pre-Orientation Group). The outcome measure was
programme attrition within 15 months. Groups were compared using Kaplan-Meier
survival analysis and Cox proportional hazards regression modelling. Patients in
the Orientation Group had a 23% increased odds of attrition compared to patients
in the Pre-Orientation group (adjusted Hazard ratio, aHR 1.23; 95% confidence
interval, CI: 1.01, 1.51) and shorter median duration of follow-up (2.0 vs. 2.9
months, P = 0.004). An increase in body mass index z-score of 1 unit resulted in
a nearly fivefold increased odds of attrition (aHR 5.24; 95% CI: 2.95, 9.3). An
orientation for new patients did not reduce attrition within 15 months. We
suggest that ongoing retention strategies should be embedded into the treatment
phase of the programme.
PMID- 27487781
TI - Focus on nutrition.
PMID- 27487782
TI - Clinical Presentation and Outcomes Associated with Different Treatment Modalities
for Pediatric Bark Scorpion Envenomation.
AB - INTRODUCTION: Scorpion envenomation is potentially life-threatening and affects
children in the Southwestern USA. An FDA-approved antivenom is available, but its
high cost has led to use of off-label antivenom dosing or supportive care alone
as alternatives to FDA-recommended dosing. This study sought to determine whether
treatment approach influences outcomes in envenomated children. METHODS: A
retrospective cohort study of children with grade III or IV scorpion envenomation
evaluated in Phoenix Children's Hospital ED between September 1, 2011, and March
31, 2014. Patients were grouped based on treatment: group 1, supportive care
only; group 2, FDA-recommended dosing (3-vial initial dose); group 3, "off label"
dosing (1-2 vial initial dose). Primary outcomes were ED length of stay and
hospital admission. Secondary outcomes were mechanical ventilation and aspiration
pneumonia. RESULTS: One hundred fifty-six patients were included with 58 patients
in group 1, 16 patients in group 2, and 82 patients in group 3. Group 1 was
significantly older than the antivenom groups (p < 0.001), and group 2 was
younger than group 3 (p = 0.024). Envenomation grade was also different, with
group 1 having fewer grade IV then groups 2 and 3 (p < 0.001). Three percent of
group 1, 56 % of group 2, and 28 % of group 3 had respiratory distress (p <
0.001). ED LOS was not significantly different between groups. Hospital admission
occurred in 3.4 % group 1, no group 2, and 8.5 % group 3 patients. Two
intubations and two aspirations occurred in group 3. CONCLUSIONS: In this study,
clinical presentation appeared to influence treatment. Groups that received
antivenom had a higher envenomation grade than the group that received supportive
care. The FDA-recommended dosing group was younger and had more respiratory
distress than those treated with initial doses of 1-2 vials. Outcomes were not
significantly different between groups. Prospective studies may identify the
ideal population for each treatment approach.
PMID- 27487783
TI - A Cluster Randomised Controlled Trial of a Brief Child Health Nurse Intervention
to Reduce Infant Secondhand Smoke Exposure.
AB - Background Exposure to secondhand smoke (SHS) is a significant contributor to ill
health in children. A study was undertaken to determine the effectiveness of two
brief multi-strategic child health nurse delivered interventions in: decreasing
the prevalence of infants exposed to SHS; decreasing the prevalence of smoking
amongst parent/carers of infants and increasing the prevalence of household
smoking bans. Methods This study was a 3 arm, cluster randomised controlled
trial. Clusters were 39 community based well child health clinics in one local
area health service. Clinics were stratified according to annual number of client
appointments and then randomly assigned in a 1:1:1 ratio, (Intervention 1:
Intervention 2: Control), with 13 clinics in each cluster. Parents/carers of
infants in the intervention groups received a brief multi-strategic intervention
from child health nurses during clinic consultations. Treatment condition 1
included computer delivered risk assessment and feedback and nurse brief advice.
Treatment condition 2 included all elements of Treatment condition 1 with the
addition of biochemical feedback of infant SHS exposure. Results When compared to
the Control group at 12 months, no significant differences in the prevalence of
infant exposure to SHS were detected from baseline to follow-up for Treatment
condition 1 (OR 1.16, 95 % CI 0.73-1.85, p = 0.53) or Treatment condition 2 (OR
1.30, 95 % CI 0.88-1.92, p = 0.19) Similarly, no significant differences were
detected in the proportion of parent/carers who reported that they were smokers
(T1:OR 0.95, 95 % CI 0.78-1.15, p = 0.58 and T2:OR 0.97, 95 % CI 0.80-1.18, p =
0.77), or in the proportion of households reported to have a complete smoking ban
(T1:OR 1.21, 95 % CI 0.89-1.64, p = 0.23 and T2:OR 1.06, 95 % CI 0.79-1.43, p =
0.68). Conclusions Further research is required to identify effective
interventions that can be consistently provided by child health nurses if the
potential of such settings to contribute to reductions in child SHS exposure is
to be realised.
PMID- 27487784
TI - Epidemiology of invasive pneumococcal infections: manifestations, incidence and
case fatality rate correlated to age, gender and risk factors.
AB - BACKGROUND: Incidence, manifestations and case-fatality rate (CFR) of invasive
pneumococcal disease (IPD) vary with age and comorbidities. New vaccines,
changing age distribution, prolonged survival among immunocompromised patients
and improved sepsis management have created a need for an update of basic facts
to inform vaccine recommendations. METHODS: Age, gender and comorbidities were
related to manifestations and death for 2977 consecutive patients with IPD in a
Swedish region with 1.5 million inhabitants during 13 years before introduction
of pneumococcal conjugate vaccines (PCV) in the infant vaccination program. These
data were related to population statistics and prevalence of several
comorbidities, and compared with two previous studies giving a total follow-up of
45 years in the same area. RESULTS: The annual incidence was 15/100,000 for any
IPD and 1.1/100,000 for meningitis; highest among elderly followed by children <
2 years. It was 2238/100,000 among myeloma patients, followed by chronic
lymphatic leukemia, hemodialysis and lung cancer, but not elevated among asthma
patients. CFR was 10 % among all patients, varying from 3 % below 18 years to 22
% >= 80 years. During 45 years, the IPD incidence increased threefold and CFR
dropped from 20 to 10 %. Meningitis incidence remained stable (1.1/100,000/year)
but CFR dropped from 33 to 13 %. IPD-specific mortality decreased among children
<2 years from 3.1 to 0.46/100,000/year but tripled among those >=65 years.
CONCLUSIONS: IPD incidence and CFR vary widely between age and risk groups and
over time even without general infant vaccination. Knowledge about specific
epidemiological characteristics is important for informing and evaluating
vaccination policies.
PMID- 27487786
TI - Therapeutic Effect of Chang'an I Recipe ( I ) on Irritable Bowel Syndrome with
Diarrhea: A Multicenter Randomized Double-Blind Placebo-Controlled Clinical
Trial.
AB - OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) decoction
Chang'an I Recipe ( I ) in the treatment of irritable bowel syndrome with
diarrhea (IBS-D). METHOD: A multicenter, randomized, double-blind, placebo
controlled clinical trial was designed. Based on the order of inclusion, the IBS
D patients were randomly assigned to the treatment group or the placebo control
group, administrated with Chang'an I Recipe or placebo, 150 mL/bag, 3 times
daily, for 8 weeks. The primary indices of efficacy included the effective rates
of IBS symptom severity score (IBS-SSS) and the differences in adequate relief
(AR) responder; the secondary indexes of efficacy included the changes in scores
of the IBS Quality of Life (IBS-QOL) and Hospital Anxiety and Depression (HAD)
scales. The safety indices included adverse events and related laboratory tests.
RESULTS: A total of 216 patients were included, with 109 in the treatment group
and 107 in the control group, and finally 206 were included in the full analysis
set (FAS), 191 were included in the per protocol set (PPS). In FAS, the total
effective rate was 67.6% and 40.2% for the treatment and control groups,
respectively, with 95% confidence interval (CI) for difference in the effective
rates between the two groups of 14.4%-40.2%; while in PPS, the total effective
rate was 71.3% and 41.2% for the treatment and control groups, respectively (95%
CI 16.6%-43.4%). The consistent conclusions of FAS and PPS showed a better
efficacy in the treatment group. Both FAS and PPS showed higher AR responder in
the treatment group (FAS: 59.6% vs. 35.5%; PPS: 62.8% vs. 38.1%). As for IBS-QOL,
the total score and scores in various dimensions of IBS-QOL were not
significantly different between the two groups (P>0.05). Both anxiety and
depression scales of HAD were not significantly different between the two groups
(P>0.05). No adverse events or laboratory abnormalities were found to be
obviously related to the tested drugs or clinically significant. CONCLUSION:
Chang'an I Recipe was more effective than placebo in the treatment of IBS-D, with
no obvious adverse reactions. (No.ChiCTR-TRC-09000328).
PMID- 27487785
TI - Neurons in the brain of the desert locust Schistocerca gregaria sensitive to
polarized light at low stimulus elevations.
AB - Desert locusts (Schistocerca gregaria) sense the plane of dorsally presented
polarized light through specialized dorsal eye regions that are likely adapted to
exploit the polarization pattern of the blue sky for spatial orientation.
Receptive fields of these dorsal rim photoreceptors and polarization-sensitive
interneurons are directed toward the upper sky but may extend to elevations below
30 degrees . Behavioral data, however, suggests that S. gregaria is even able to
detect polarized light from ventral directions but physiological evidence for
this is still lacking. In this study we characterized neurons in the locust brain
showing polarization sensitivity at low elevations down to the horizon. In most
neurons polarization sensitivity was absent or weak when stimulating from the
zenith. All neurons, including projection and commissural neurons of the optic
lobe and local interneurons of the central brain, are novel cell types, distinct
from polarization-sensitive neurons studied so far. Painting dorsal rim areas in
both eyes black to block visual input had no effect on the polarization
sensitivity of these neurons, suggesting that they receive polarized light input
from the main eye. A possible role of these neurons in flight stabilization or
the perception of polarized light reflected from bodies of water or vegetation is
discussed.
PMID- 27487787
TI - Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel
Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents.
AB - BACKGROUND: Histone deacetylase (HDAC) inhibitors can reactivate gene expression
and inhibit the growth and survival of cancer cells. OBJECTIVE: To identify the
important pharmacophoric features and correlate 3Dchemical structure with
biological activity using 3D-QSAR and Pharmacophore modeling studies. METHOD: The
pharmacophore hypotheses were developed using e-pharmacophore script and phase
module. Pharmacophore hypothesis represents the 3D arrangement of molecular
features necessary for activity. A series of 55 compounds with wellassigned HDAC
inhibitory activity were used for 3D-QSAR model development. RESULTS: Best 3D
QSAR model, which is a five partial least square (PLS) factor model with good
statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811), cross
validated coefficient rcv 2=0.9807 and R2 pred=0.7147 with low standard deviation
(0.0952). Additionally, the selected pharmacophore model DDRRR.419 was used as a
3D query for virtual screening against the ZINC database. In the virtual
screening workflow, docking studies (HTVS, SP and XP) were carried out by
selecting multiple receptors (PDB ID: 1T69, 1T64, 4LXZ, 4LY1, 3MAX, 2VQQ, 3C10,
1W22). Finally, six compounds were obtained based on high scoring function (dock
score -11.2278-10.2222 kcal/mol) and diverse structures. CONCLUSION: The
structure activity correlation was established using virtual screening, docking,
energetic based pharmacophore modelling, pharmacophore, atom based 3D QSAR models
and their validation. The outcomes of these studies could be further employed for
the design of novel HDAC inhibitors for anticancer activity.
PMID- 27487788
TI - Identification of Novel Structurally Diverse Anaplastic Lymphoma Kinase
Inhibitors Based on Pharmacophore Modeling, Virtual Screening and Molecular
Docking.
AB - AIM AND OBJECTIVE: Anaplastic lymphoma kinase, an insulin receptor protein
tyrosine kinase, is a very attractive receptor protein target for anticancer
therapy. This study was undertaken to identify novel structurally diverse
anaplastic lymphoma kinase inhibitors. MATERIAL AND METHOD: Pharmacophore
hypotheses modeling, virtual screening and molecular docking were used to detect
potential inhibitors of anaplastic lymphoma kinase in this paper. RESULTS: After
the generation of ten pharmacophore hypotheses, Hypo1 with the highest
correlation value (0.981), lowest RMS (0.565), highest cost difference (83.850)
along with four typical chemical features was regarded as the best hypothesis.
Hypo1 contains a hydrogen bond acceptor, a hydrogen bong donor, a hydrophobic and
a ring aromatic feature. And then, hypo1 was validated and used to screen three
databases after screened by Lipinski's rule of five. 3015 hits screened by Hypo1
were submitted to molecular docking based on the crystal structure of anaplastic
lymphoma kinase. CONCLUSION: all the seven molecules formed hydrogen bond
interaction with Met1199 as well as formed several other hydrogen bond
interactions with different residues. All of them formed Van Der Waals
interaction with hydrophobic pocket which made up of residues of Ala1148,
Leu1256, Leu1196, Leu1198 Val1130 and Val1180. Some of them also formed van der
Waals interaction in somewhere else of protein pocket.
PMID- 27487790
TI - [MIF in post-resuscitation syndrome : No marker of inflammation, but of tissue
damage].
PMID- 27487789
TI - Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ.
AB - BACKGROUND: Germ cell neoplasia in situ (GCNIS), is preinvasive stage of
testicular germ cell tumours (TGCTs). Fibrillins, which are integral components
of microfibrils are suggested to be involved in cancer pathogenesis and
maintenance of embryonic stem cells pluripotency. The aim of this study was to
examine fibrillin-1 (FBN-1) expression in TGCTs patients. METHODS: Surgical
specimens from 203 patients with TGCTs were included into the translational
study. FBN-1 expression was evaluated in the tumour tissue, in GCNIS and in
adjacent non-neoplastic testicular tissue in all available cases. Tissue samples
were processed by the tissue microarray method. FBN-1 was detected by
immunohistochemistry using goat polyclonal antibody and the expression was
evaluated by the multiplicative quickscore (QS). RESULTS: The highest FBN-1
positivity was detected in GCNIS (mean QS = 11.30), with overexpression of FBN-1
(QS >9) in the majority (77.1 %) of cases. Expression of FBN-1 in all subtypes of
TGCTs was significantly lower in comparison to expression in GCNIS (all p
<0.001). Seminoma had significantly higher expression compared to EC, ChC and TER
(all p <0.05), but not to YST (p = 0.84). In non-neoplastic testicular tissue the
FBN-1 positivity was very low (mean QS = 0.02). Sensitivity, specificity,
positive and negative predictive value of FBN-1 expression for diagnosis of GCNIS
were 97.1, 98.8, 98.6 and 97.7 %. CONCLUSIONS: FBN-1 is overexpressed in TGCTs
and especially in GCNIS when compared to non-neoplastic testicular tissue in
patients with germ cell tumors and could be involved in germ cell neoplasia in
situ development.
PMID- 27487791
TI - Aluminium salalens vs. salans: "Initiator Design" for the isoselective
polymerisation of rac-lactide.
AB - We report the rationalised design of aluminium initiators and their application
for ROP of rac-lactide (rac-LA). A very minor change to the ligand backbone
(imine reduction) to give secondary amines was found to have a dramatic effect on
activity and selectivity with isotactic PLA being realised.
PMID- 27487792
TI - Clinical interventions for venous leg ulcers: Proposals to improve the quality of
clinical leg ulcer research.
AB - The present status of clinical leg ulcer healing research was reviewed by 25
experts over 2 days on September 28 and 29, 2015. Multiple clinical effectiveness
reviews were presented suggesting that published clinical wound healing research
often does not meet present (2015) evidence based standards. Specific areas
requiring remediation were highlighted and approaches to overcoming existing
challenges were proposed. Participants using anonymous voting technology
developed an action plan to resolve perceived deficiencies. Statements were
accepted if 75% of participants agreed. Older patients with a high frequency of
comorbid conditions posed particular difficulties in designing clinical research
protocols and better diagnostic categorization is necessary A standardized model
template for collecting information about diagnosis and evaluation of the effect
of interventions on healing of all types of leg ulcers was considered a high
priority. Such a model template could be modified depending on the specific
etiology of the leg ulcers. Generally agreed on quantifiable standards to
establish degree of morbidity was considered a high priority. There was universal
agreement that sources of funding and conflicts of interest needed to be
disclosed in presentations and all publications. All clinical research studies
should be registered with appropriate authorities. There was substantial
enthusiasm for a clinical research network with quality standards for membership
and an advisory research core available to investigators. Such a network should
be funded and actively managed to insure long-term viability. The governance of
such an entity needs to be established by the wound care community. The present
trend to integrate patients into the clinical research process was endorsed and
there was enthusiasm to develop patient advocacy for wound healing research.
PMID- 27487793
TI - Evolving Concepts in Phases I and II Drug Development for Crohn's Disease.
AB - The highest attrition rates during drug development programmes occur at the proof
of concept stage. Given the large number of molecules under development for
Crohn's disease, a need exists to improve the efficiency of early drug
development by fast-tracking promising agents and terminating ineffective ones.
Multiple opportunities are available to achieve these goals, including the use of
more responsive outcome measures, and the incorporation of sophisticated
pharmacokinetic modelling and/or highly specific pharmacodynamic markers into
exposure-based dosing regimens and novel trial designs. In this article we review
these strategies and propose an integrated paradigm of early drug development in
Crohn's disease.
PMID- 27487794
TI - Early Splenic Flexure Intubation Competency Predicts Early Cecal Intubation
Competency in Gastroenterology Fellows.
AB - BACKGROUND: Trainees learn colonoscopy skills at varying speeds. We hypothesized
that a fellow's ability to reliably reach the splenic flexure early in training
could predict the number of procedures required to achieve competency in
intubating the cecum. METHODS: This was a retrospective analysis of prospectively
collected data. The most proximal site in the colon reached independently by GI
fellows was recorded on consecutive colonoscopies. The number of procedures
required to achieve splenic flexure intubation rate (SFIR) >= 90 % by cumulative
summation learning curve and cecal intubation rate (CIR) >= 90 % by rolling
average was calculated. Fellows were then dichotomized into "Early" versus "Late"
learners based on the median number of procedures required to achieve SFIR >= 90
%. The number of procedures required to achieve CIR >= 90 % was then compared
between the groups. RESULTS: Fellows achieved SFIR >= 90 % at a median of 37
colonoscopies. Fellows who achieved SFIR competency early achieved CIR >= 90 % at
a mean of 208 procedures versus 352 procedures in the fellows who achieved SFIR
competency late (p = 0.03). CONCLUSIONS: Data from a single academic medical
center show that whether a trainee will learn endoscopy quickly compared to
his/her peers can be predicted early in their endoscopy training by tracking
SFIR. This knowledge could be used to customize endoscopy curriculum.
PMID- 27487795
TI - Safety and Efficacy of a Same-Day Low-Volume 1 L PEG Bowel Preparation in
Colonoscopy for the Elderly People and People with Renal Dysfunction.
AB - INTRODUCTION: A same-day low-volume 1 L polyethylene glycol (PEG) for bowel
preparation before colonoscopy was developed to improve patients' compliance. We
aimed to evaluate the efficacy and safety of this regimen especially for the
elderly and patients with renal dysfunction. METHODS: All consecutive patients
who underwent colonoscopy in our center from November 2014 to September 2015 were
included. Patients undertook a low-residue diet with 10 mL sodium picosulfate 1
day before colonoscopy. Subsequently, they had 1 L low-volume PEG (MoviPrep) and
0.5 L water 4 h before the examination. Clinical outcomes, including cleansing
level using the Boston bowel preparation score (BBPS), in the elderly and special
elderly (65-79 and >=80 years old) were analyzed and compared with the non
elderly (18-64 years old). Additionally, patients with renal dysfunction were
analyzed with respect to both complications and changes in blood parameters.
RESULTS: A total of 5427 patients (mean age: 64.5 +/- 13.8) were analyzed. The
rate of BBPS >= 6 in the elderly (2761 patients), special-elderly (565 patients),
and non-elderly (2101 patients) was 94.1, 91.8, and 94.6 %, respectively. In the
special-elderly, the rate of renal dysfunction was 14.8 %, and no severe
complications were detected after colonoscopy. Additionally, there were no severe
complications in 86 patients with renal dysfunction, though elevation of
hematocrit was shown after intake of 1 L PEG (before, 36.7 +/- 6.1 vs. after,
39.0 +/- 5.7, P = 0.006). CONCLUSIONS: Our study shows the safety and efficacy of
same-day low-volume 1 L PEG bowel preparation in colonoscopy for the elderly and
patients with renal dysfunction.
PMID- 27487796
TI - Fully Automated Evaluation of Total Glomerular Number and Capillary Tuft Size in
Nephritic Kidneys Using Lightsheet Microscopy.
AB - The total number of glomeruli is a fundamental parameter of kidney function but
very difficult to determine using standard methodology. Here, we counted all
individual glomeruli in murine kidneys and sized the capillary tufts by combining
in vivo fluorescence labeling of endothelial cells, a novel tissue-clearing
technique, lightsheet microscopy, and automated registration by image analysis.
Total hands-on time per organ was <1 hour, and automated counting/sizing was
finished in <3 hours. We also investigated the novel use of ethyl-3-phenylprop-2
enoate (ethyl cinnamate) as a nontoxic solvent-based clearing reagent that can be
handled without specific safety measures. Ethyl cinnamate rapidly cleared all
tested organs, including calcified bone, but the fluorescence of proteins and
immunohistochemical labels was maintained over weeks. Using ethyl cinnamate
cleared kidneys, we also quantified the average creatinine clearance rate per
glomerulus. This parameter decreased in the first week of experimental
nephrotoxic nephritis, whereas reduction in glomerular numbers occurred much
later. Our approach delivers fundamental parameters of renal function, and
because of its ease of use and speed, it is suitable for high-throughput analysis
and could greatly facilitate studies of the effect of kidney diseases on whole
organ physiology.
PMID- 27487797
TI - Association between vitamin D deficiency and pre-existing resistance-associated
hepatitis C virus NS5A variants.
AB - AIM: Although interferon-free therapy with direct-acting antivirals has developed
as a standard of care for chronic hepatitis C, the existence of resistance
associated variants (RAVs) has a negative impact on treatment results. Recently,
several studies indicated a relationship between chronic hepatitis C and serum
vitamin D levels. However, the relationship between RAVs at the hepatitis C virus
non-structure 5A (NS5A) region and serum vitamin D level has not yet been
examined. METHODS: Among patients with genotype 1 chronic hepatitis C who were
enrolled in a multicenter cooperative study, our subjects comprised 247 patients
in whom it was possible to measure RAVs at the NS5A region. These RAVs were
measured using a direct sequencing method. RESULTS: The median age of patients
was 70 years (range, 24-87 years), and the number of female patients was 135
(54.7%). The median serum 25(OH) D3 level was 22 ng/mL (range, 6-64 ng/mL). L31
and Y93 RAVs at the NS5A region were detected in 3.7% (9/247) and 13.4% (33/247)
of patients, respectively. Multivariate analysis identified vitamin D deficiency
(serum 25(OH) D3 <= 20 ng/mL) (P = 5.91 * 10-5 , odds ratio = 5.015) and elderly
age (>70 years) (P = 1.85 * 10-3 , odds ratio = 3.364) as contributing
independent factors associated with the presence of the L31 and/or Y93 RAVs. The
Y93H RAV was detected in 25.9% (29/112) of patients with a vitamin D deficiency,
and in 8.9% (12/135) of those with a serum 25(OH) D3 level >20 ng/mL (P = 4.90 *
10-3 ). CONCLUSION: We showed that RAVs at the NS5A region are associated with
vitamin D deficiency and elderly age, which may have a negative influence on
innate/adaptive immune responses to hepatitis C virus infection.
PMID- 27487798
TI - A 24-channel shim array for the human spinal cord: Design, evaluation, and
application.
AB - PURPOSE: A novel multichannel shim array is introduced to improve MRI and
spectroscopic studies of the human spinal cord. METHODS: Twenty-four-channel shim
and 8-channel transceiver arrays were designed to insert into the patient bed
table to lie in close proximity to the subject's spine. The reference field
patterns of each of the shim channels (Hz/A) were determined empirically via
gradient echo field mapping and subsequently used to demonstrate shim performance
at 3 Tesla using an ex vivo phantom, which incorporated a fixed human spine. The
shim was further demonstrated on five healthy volunteers. RESULTS: Application of
the shim to the ex vivo phantom reduced the standard deviation of the field over
the spinal volume of interest (123.4 cm3 ) from an original 51.3 Hz down to 32.5
Hz, amounting to an improvement in field homogeneity of 36.6%. In vivo, the spine
shim resulted in an average improvement in field homogeneity of 63.8 +/- 15.4%.
CONCLUSION: The localized spine shim offers a promising new means of correcting
magnetic field distortion in the spinal cord. Magn Reson Med 76:1604-1611, 2016.
(c) 2016 International Society for Magnetic Resonance in Medicine.
PMID- 27487799
TI - Efmoroctocog Alfa: A Review in Haemophilia A.
AB - Efmoroctocog alfa (Elocta((r)), Eloctate((r)), EloctateTM), a first-in-class
recombinant factor VIII-Fc fusion protein (rFVIIIFc), has an extended half-life
compared with conventional factor VIII (FVIII) preparations, including
recombinant FVIII (rFVIII) products. It is approved for the treatment and
prophylaxis of bleeding in patients with haemophilia A in multiple countries
worldwide. Data accumulated from pivotal phase III studies (A-LONG in adults and
adolescents aged >=12 years; Kids A-LONG in children aged <12 years) and their
ongoing extension study (ASPIRE) have demonstrated the long-term effectiveness of
efmoroctocog alfa for the treatment of acute bleeding episodes, perioperative
management and routine prophylaxis in previously treated males with severe
haemophilia A. Among patients on individualized efmoroctocog alfa prophylaxis who
had previously received FVIII prophylaxis, all but one of those aged >=12 years
and three-quarters of those aged <12 years reduced their injection frequency
compared with their pre-study regimen. FVIII replacement therapy with
efmoroctocog alfa was generally well tolerated in previously treated patients,
with no evidence of increased immunogenicity. The safety and efficacy of FVIII
replacement therapy with efmoroctocog alfa in previously untreated males aged <6
years with severe haemophilia A are currently being evaluated. Although there are
no direct, head-to-head studies, the available clinical trial evidence indicates
that efmoroctocog alfa provides an effective alternative to conventional FVIII
preparations (including rFVIIIs) for the management of haemophilia A. Moreover,
by reducing the frequency of injections required, it has the potential to reduce
treatment burden, and hence improve adherence to prophylaxis.
PMID- 27487800
TI - A 1.35 Mb DNA fragment is inserted into the DHMN1 locus on chromosome 7q34-q36.2.
AB - Distal hereditary motor neuropathies predominantly affect the motor neurons of
the peripheral nervous system leading to chronic disability. Using whole genome
sequencing (WGS) we have identified a novel structural variation (SV) within the
distal hereditary motor neuropathy locus on chromosome 7q34-q36.2 (DHMN1). The SV
involves the insertion of a 1.35 Mb DNA fragment into the DHMN1 disease locus.
The source of the inserted sequence is 2.3 Mb distal to the disease locus at
chromosome 7q36.3. The insertion involves the duplication of five genes
(LOC389602, RNF32, LMBR1, NOM1, MNX1) and partial duplication of UBE3C. The
genomic structure of genes within the DHMN1 locus are not disrupted by the
insertion and no disease causing point mutations within the locus were
identified. This suggests the novel SV is the most likely DNA mutation disrupting
the DHMN1 locus. Due to the size and position of the DNA insertion, the gene(s)
directly affected by the genomic re-arrangement remains elusive. Our finding
represents a new genetic cause for hereditary motor neuropathies and highlights
the growing importance of interrogating the non-coding genome for SV mutations in
families which have been excluded for genome wide coding mutations.
PMID- 27487801
TI - Genome-wide scans reveal variants at EDAR predominantly affecting hair
straightness in Han Chinese and Uyghur populations.
AB - Hair straightness/curliness is one of the most conspicuous features of human
variation and is particularly diverse among populations. A recent genome-wide
scan found common variants in the Trichohyalin (TCHH) gene that are associated
with hair straightness in Europeans, but different genes might affect this
phenotype in other populations. By sampling 2899 Han Chinese, we performed the
first genome-wide scan of hair straightness in East Asians, and found EDAR
(rs3827760) as the predominant gene (P = 4.67 * 10-16), accounting for 3.66 % of
the total variance. The candidate gene approach did not find further significant
associations, suggesting that hair straightness may be affected by a large number
of genes with subtle effects. Notably, genetic variants associated with hair
straightness in Europeans are generally low in frequency in Han Chinese, and vice
versa. To evaluate the relative contribution of these variants, we performed a
second genome-wide scan in 709 samples from the Uyghur, an admixed population
with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR
(rs3827760: P = 1.92 * 10-12) and TCHH (rs11803731: P = 1.46 * 10-3) are
associated with hair straightness, but EDAR (OR 0.415) has a greater effect than
TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P =
0.645), suggesting that these two genes affect hair straightness through
different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not
subject to selection. While EDAR is under strong selection in East Asia, it does
not appear to be subject to selection after the admixture in Uyghurs. These
suggest that hair straightness is unlikely a trait under selection.
PMID- 27487803
TI - Effects of temperature and diet on length-weight relationship and condition
factor of the juvenile Malabar blood snapper (Lutjanus malabaricus Bloch &
Schneider, 1801).
AB - In this study we aimed to analyze the effects of water temperature and diet on
the length-weight relationship and condition of juvenile Malabar blood snapper
Lutjanus malabaricus over a 30-d experimental period. The experiment was
conducted in the laboratory using a flow-through-sea-water system. The fish were
subjected to four different temperatures (22, 26, 30, and 34 degrees C) and two
diets (commercial pellet and natural shrimp). Fish were fed twice daily. L.
malabaricus exhibited negative allometric growth (b<3) at the beginning of the
experiment (Day 0) at all temperatures and both diets except for 22 degrees C
fed with shrimp, which showed isometric growth (b=3). Conversely, at the end of
the experiment (Day 30) fish showed isometric growth (b=3) at 30 degrees C fed
with the pellet diet, indicating that the shape of the fish did not change with
increasing weight and length, and a positive allometric growth (b>3) at 30
degrees C fed with shrimp diet, which indicated that fish weight increases faster
than their length. The rest of the temperatures represented negative allometric
growth (b<3) on both diet, meaning that fish became lighter with increasing size.
The condition factors in the initial and final measurements were greater than 1,
indicating the state of health of the fish, except for those fed on a pellet diet
at 34 degrees C. However, the best condition was obtained at 30 degrees C on
both diets. Nevertheless, diets did not have a significant effect on growth and
condition of juvenile L. malabaricus. The data obtained from this study suggested
culturing L. malabaricus at 30 degrees C and feeding on the pellet or shrimp
diet, which will optimize the overall production and condition of this
commercially important fish species.
PMID- 27487802
TI - Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic
adaptation and potential probiotic profiles.
AB - OBJECTIVE: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic
properties, such as antimicrobial activity against various pathogens and the
capacity to significantly improve pig growth and pork quality. The purpose of
this study was to reveal the genes potentially related to its genetic adaptation
and probiotic profiles based on comparative genomic analysis. METHODS: The genome
sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum
strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for
genome alignment and comparison. CRISPRFinder was applied for searching the
clustered regularly interspaced short palindromic repeats (CRISPRs). RESULTS: We
identified genes that encode proteins related to genetic adaptation and probiotic
profiles, including carbohydrate transport and metabolism, proteolytic enzyme
systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses,
bile salt resistance, ability to adhere to the host intestinal wall,
exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. CONCLUSIONS:
Comparative characterization of the L. plantarum ZJ316 genome provided the
genetic basis for further elucidating the functional mechanisms of its probiotic
properties. ZJ316 could be considered a potential probiotic candidate.
PMID- 27487804
TI - Association of VIPR-1 gene polymorphisms and haplotypes with egg production in
laying quails.
AB - The laying quail is a worldwide breed which exhibits high economic value. In our
current study, the vasoactive intestinal peptide receptor-1 (VIPR-1) was selected
as the candidate gene for identifying traits of egg production. A single
nucleotide polymorphism (SNP) detection was performed in 443 individual quails,
including 196 quails from the H line, 202 quails from the L line, and 45 wild
quails. The SNPs were genotyped using a polymerase chain reaction-restriction
fragment length polymorphism (PCR-RFLP). Two mutations (G373T, A313G) were
detected in all the tested quail populations. The associated analysis showed that
the SNP genotypes of the VIPR-1 gene were significantly linked with the egg
weight of G373T and A313G in 398 quails. The quails with the genotype GG always
exhibited the largest egg weight for the two mutations in the H and L lines.
Linkage disequilibrium (LD) analysis indicated that G373T and A313G loci showed
the weakest LD. Seven main diplotypes from the four main reconstructed haplotypes
were observed, indicating a significant association of diplotypes with egg
weight. Quails with the h1h2 (GGGT) diplotype always exhibited the smallest egg
weight and largest egg number at 20 weeks of age. The overall results suggest
that the alterations in quails may be linked with potential major loci or genes
affecting reproductive traits.
PMID- 27487805
TI - Probiotic properties of lactic acid bacteria isolated from traditionally
fermented Xinjiang cheese.
AB - Six lactic acid bacterial (LAB) strains were isolated from traditionally
fermented Xinjiang cheese and evaluated for functional and probiotic properties
and potentials as starter cultures. The isolated six LAB strains comprised
Lactobacillus rhamnosus (one strain), Lactobacillus helveticus (one strain), and
Enterococcus hirae (four strains). All of the six strains were tolerant to acidic
and bile salt conditions. Among which, the L. rhamnosus R4 strain showed more
desirable antimicrobial, auto-aggregation, and hydrophobic activity. In addition,
the strain L. rhamnosus R4 exhibited the highest level of free radical scavenging
activity (53.78% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and 45.79%
of hydroxyl radicals). L. rhamnosus R4 also demonstrated cholesterol and
triglyceride degradation by 50.97% and 28.92%, respectively. To further examine
the health-promoting effects of these LAB strains on host lifespan,
Caenorhabditis elegans was used as an in vivo model. Worms fed LAB as a food
source had significant differences in lifespan compared to those fed Escherichia
coli OP50 (as a negative control). Feeding of L. rhamnosus R4 extended the mean
lifespan of C. elegans by up to 36.1% compared to that of the control. The
results suggest that the strains isolated from Xinjiang fermented dairy products
have high potential as starter cultures in the cheese industry.
PMID- 27487806
TI - Chryseobacterium chengduensis sp. nov. isolated from the air of captive giant
panda enclosures in Chengdu, China.
AB - A Gram-negative, aerobic, non-motile, rod-shaped bacterial strain, designated 25
1(T), was isolated from the air inside giant panda enclosures at the Chengdu
Research Base of Giant Panda Breeding, China. Strain 25-1(T) grew optimally at pH
7.0-8.0, at 28-30 degrees C and in the presence of NaCl concentrations from 0.0%
to 0.5 %. 16S rRNA gene sequence analysis indicated that strain 25-1(T) belongs
to the genus Chryseobacterium within the family Flavobacteriaceae and is related
most closely to C. carnis G81(T) (96.4% similarity), C. lathyri RBA2-6(T) (95.8%
similarity), and C. zeae JM1085(T) (95.8% similarity). Its genomic DNA G+C molar
composition was 36.2%. The major cellular fatty acids were iso-C15:0 (44.0%), iso
C17:0 3OH (19.8%) and C16:1 omega7c/16:1 omega6c (12.7%). The only isoprenoid
quinone was menaquinone 6 (MK-6). The major polar lipids were
phosphatidylethanolamine, two unidentified amino lipids and two unidentified
lipids. The DNA-DNA relatedness between strain 25-1(T) and C. lathyri RBA2-6(T)
was 38%. Phenotypic, genotypic, and phylogenetic characteristics indicated that
strain 25-1(T) is a novel member of the genus Chryseobacterium, for which the
name C. chengduensis sp. nov. is proposed. The type strain is 25-1(T) (CCTCC
AB2015133(T)=DSM 100396(T)).
PMID- 27487807
TI - Statistical culture-based strategies to enhance chlamydospore production by
Trichoderma harzianum SH2303 in liquid fermentation.
AB - Trichoderma-based formulations are applied as commercial biocontrol agents for
soil-borne plant pathogens. Chlamydospores are active propagules in Trichoderma
spp., but their production is currently limited due to a lack of optimal liquid
fermentation technology. In this study, we explored response surface
methodologies for optimizing fermentation technology in Trichoderma SH2303. Our
initial studies, using the Plackett-Burman design, identified cornmeal, glycerol,
and initial pH levels as the most significant factors (P<0.05) for enhancing the
production of chlamydospores. Subsequently, we applied the Box-Behnken design to
study the interactions between, and optimal levels of, a number of factors in
chlamydospore production. These statistically predicted results indicated that
the highest number of chlamydospores (3.6*10(8) spores/ml) would be obtained
under the following condition: corn flour 62.86 g/L, glycerol 7.54 ml/L, pH 4.17,
and 6-d incubation in liquid fermentation. We validated these predicted values
via three repeated experiments using the optimal culture and achieved maximum
chlamydospores of 4.5*10(8) spores/ml, which approximately a 8-fold increase in
the number of chlamydospores produced by T. harzianum SH2303 compared with that
before optimization. These optimized values could help make chlamydospore
production cost-efficient in the future development of novel biocontrol agents.
PMID- 27487808
TI - Emergy assessment of three home courtyard agriculture production systems in Tibet
Autonomous Region, China.
AB - Home courtyard agriculture is an important model of agricultural production on
the Tibetan plateau. Because of the sensitive and fragile plateau environment, it
needs to have optimal performance characteristics, including high sustainability,
low environmental pressure, and high economic benefit. Emergy analysis is a
promising tool for evaluation of the environmental-economic performance of these
production systems. In this study, emergy analysis was used to evaluate three
courtyard agricultural production models: Raising Geese in Corn Fields (RGICF),
Conventional Corn Planting (CCP), and Pea-Wheat Rotation (PWR). The results
showed that the RGICF model produced greater economic benefits, and had higher
sustainability, lower environmental pressure, and higher product safety than the
CCP and PWR models. The emergy yield ratio (EYR) and emergy self-support ratio
(ESR) of RGICF were 0.66 and 0.11, respectively, lower than those of the CCP
production model, and 0.99 and 0.08, respectively, lower than those of the PWR
production model. The impact of RGICF (1.45) on the environment was lower than
that of CCP (2.26) and PWR (2.46). The emergy sustainable indices (ESIs) of RGICF
were 1.07 and 1.02 times higher than those of CCP and PWR, respectively. With
regard to the emergy index of product safety (EIPS), RGICF had a higher safety
index than those of CCP and PWR. Overall, our results suggest that the RGICF
model is advantageous and provides higher environmental benefits than the CCP and
PWR systems.
PMID- 27487809
TI - Effect of Tai Chi exercise on blood lipid profiles: a meta-analysis of randomized
controlled trials.
AB - OBJECTIVE: Studies have demonstrated that Tai Chi exercise improves blood lipid
level with inconsistent results. A meta-analysis was conducted to quantify the
effects of Tai Chi on blood lipid profiles in humans. METHODS: We screened the
databases of PubMed, EMBASE, Cochrane Library (Central), Web of Science, China
National Knowledge Infrastructure (CNKI), Wanfang data, and Clinicaltrials.gov
for randomized controlled trials with Physiotherapy Evidence Database (PEDro)
score more than 3 points up to June 2015. Six studies involving 445 subjects were
included. Most trials applied 12-week Tai Chi intervention courses. RESULTS: In
comparison with the control group, blood triglyceride (TG) level difference
between follow-up and baseline was statistically significantly lower in the Tai
Chi practicing group (weighted mean difference (WMD) -16.81 mg/dl; 95% confidence
intervals (CI) -31.27 to -2.35 mg/dl; P=0.02). A trend to improving total
cholesterol (TC) reduction was found with Tai Chi (WMD -7.96 mg/dl; 95% CI -17.30
to 1.39 mg/dl; P=0.10). However, no difference was found in blood low-density
lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C).
CONCLUSIONS: Tai Chi exercise lowered blood TG level with a trend to decrease
blood TC level. Our data suggest that Tai Chi has the potential to implement
meaningful blood lipid modification and serve as an adjunctive exercise modality.
The relationship between Tai Chi exercise regimen and lipid profile change might
have a scientific priority for future investigation.
PMID- 27487810
TI - Anticoagulation versus antiplatelet or no therapy in patients undergoing
bioprosthetic valve implantation: a systematic review and meta-analysis.
AB - OBJECTIVE: Use of vitamin K antagonist (VKA) versus antiplatelet (AP)/no therapy
following bioprosthetic valve implantation remains controversial. The aims of the
current study were to (a) systematically review the published literature
comparing the use of VKA versus AP/no treatment in such patients and (b) perform
a meta-analysis of the risks and benefits of using a VKA compared with AP/no
therapy. METHODS: Five databases were searched including PubMed, Medline, Embase,
Ovid and Cochrane for randomised clinical trials and observational studies
comparing VKA (group I) versus AP/no therapy (group II). Outcome was after
surgical intervention. Mantel-Haenszel odds ratio (OR) was calculated using
random-effects meta-analysis for the outcome. Heterogeneity was assessed by I2
statistics. A total of 14 studies were included (two randomised trials, 12
observational studies and one conference abstract, 31 740 patients). RESULTS:
Between groups I (VKA) and II (AP/no therapy), there were no differences in
thromboembolic events (145 (1%) vs 262 (1.5%), OR 0.96 (95% CI 0.60 to 1.52)),
all-cause mortality (351 (3.5%) vs 415 (2.9%), OR 1.48 (95% CI 0.87 to 2.50)) or
need for redo surgery (47 (3.3%) vs 55 (3.2%); OR 0.81 (95% CI 0.42 to 1.58)).
However, there were more bleeding events in group I versus group II (292 (2.6%)
vs 189 (1.1%); OR 2.26 (95% CI 1.67 to 3.05)). CONCLUSIONS: In a meta-analysis of
randomised and observational studies of VKA versus AP/no treatment in patients
undergoing bioprosthetic valve implantation, there was no benefit of adding a VKA
regarding thromboembolism or mortality. However, use of a VKA was associated with
increased risk of major bleeding.
PMID- 27487811
TI - Histone deacetylase inhibitors interfere with angiogenesis by decreasing
endothelial VEGFR-2 protein half-life in part via a VE-cadherin-dependent
mechanism.
AB - Recent evidence suggests that histone deacetylase inhibitors (HDACi) may mediate
part of their antitumor effects by interfering with tumor angiogenesis. As
signalling via the vascular endothelial growth factor receptor-2 (VEGFR-2)
pathway is critical for angiogenic responses during tumor progression, we
explored whether established antitumor effects of HDACi are partly mediated
through diminished endothelial VEGFR-2 expression. We therefore examined the
potential impact of three different HDACi, trichostatin A (TSA), sodium butyrate
(But) and valproic acid (VPA), on VEGFR-2 protein expression. TSA, VPA and But
significantly inhibit VEGFR-2 protein expression in endothelial cells. Pertinent
to these data, VEGFR-2 protein half-life is shown to be decreased in response to
HDACi. Recently, it could be demonstrated that expression of VE-cadherin
influences VEGFR-2 protein half-life. In our experiments, VEGFR-2 downregulation
was accompanied by HDACi-induced VE-cadherin suppression. Interestingly, siRNA
mediated knockdown of VE-cadherin led to a pronounced loss of VEGFR-2 expression
on the protein as well as on the mRNA level, implicating that VE-cadherin not
only influences VEGFR-2 protein half-life but also the transcriptional level. To
further distinguish which of the eight different histone deacetylases are
responsible for the regulation of VEGFR-2 expression, specific HDAC genes were
silenced by transfecting respective siRNAs. These studies revealed that HDACs 1,
4, 5 and 6 are preferentially involved in VEGFR-2 expression. Therefore, these
results provide an explanation for the anti-angiogenic action of HDAC inhibitors
via a VE-cadherin, HDAC 1 and HDACs 4-6-mediated suppression of VEGFR-2
expression and might be of importance in the development of new anti-angiogenic
drugs.
PMID- 27487813
TI - Emotion: Exciting extinction.
PMID- 27487812
TI - Thrombin Activable Fibrinolysis Inhibitor in Beta Thalassemia.
AB - OBJECTIVES: To study plasma levels of Thrombin activable fibrinolysis inhibitor
(TAFI) in children with beta-thalassemia major. METHODS: Fifty beta-thalassemia
major patients, 1.4 to 17 y of age, with number of transfusions received varying
from 21 to 162 were selected at random and complete blood count (CBC),
coagulation parameters [Prothrombin time (PT), Activated partial thromboplastin
time (aPTT), fibrinogen, D-dimer, protein C, protein S, antithrombin, Tissue
plasminogen activator (t-PA), Plasminogen activator inhibitor (PAI-1)] and TAFI
were performed. RESULTS: PT and aPTT were prolonged in 18 % and 30 % of cases
respectively. Reduced activity of Protein C (PC) was observed in 50 % of cases
and Protein S (PS) was reduced in 54 % of cases. t-PA levels were significantly
higher in cases. TAFI levels were 17.24 +/- 4.05 ng/ml which were significantly
higher than the control group (15.01 +/- 3.28; p = 0.003) No significant
correlation of TAFI was observed with Hb, platelet counts, liver enzymes, serum
ferritin, PC, PS, D-dimer, t-PA or PAI-1. CONCLUSIONS: There is an ongoing
subclinical activation of coagulation cascade and fibrinolytic system in
thalassemia major (TM) patients. Higher levels of TAFI in the present study with
no significant correlation with other parameters were noted, thus pointing out to
its independent role in contribution to hypercoagulable state in thalassemia.
TAFI serves as a link between two limbs of hemostasis, with its higher levels
promoting inhibition of fibrinolytic system and thus promoting a hypercoagulable
state. Performing TAFI levels in thalassemic patients could help to detect the
early coagulopathy in these patients and hence these patients can be closely
monitored for any evidence of thrombosis.
PMID- 27487814
TI - Neuroimmunology: Social support from the immune system.
PMID- 27487815
TI - Mechanistic insight on (E)-methyl 3-(2-aminophenyl)acrylate cyclization reaction
by multicatalysis of solvent and substrate.
AB - The reaction mechanism of (E)-methyl 3-(2-aminophenyl)acrylate (A) with
phenylisothiocyanate (B) as well as the vital roles of substrate A and solvent
water were investigated under unassisted, water-assisted, substrate A-assisted,
and water-A-assisted conditions. The reaction proceeds with four processes via
nucleophilic addition, deprotonation and protonation, intramolecular cyclization
with hydrogen transfer, and keto-enol tautomerization. According to the different
H-shift mode, two possible types of H-shift P1 and P2 are carefully investigated
to identify the most preferred pathway, differing in the ?NH2 group deprotonation
and ?CH group of A protonation processes. It is found that substrate A and water
not only act as reactant and solvent, but also as catalyst, proton shuttle, and
stabilizer in effectively lowering the energy barrier. Therefore, the results
demonstrate that the strong donating and accepting ability of ?NH2 group on A and
the presence of bulk water are the keys to the title reaction proceed. (c) 2016
Wiley Periodicals, Inc.
PMID- 27487816
TI - Effect of Ginkgo Biloba Extract on the Pharmacokinetics and Metabolism of
Clopidogrel in Rats.
AB - Ginkgo biloba extract (GBE), a traditional herbal product used worldwide as both
medicine and supplement, is often supplied with clopidogrel for the treatment of
cerebrovascular diseases. The aim of the current study was to explore the effect
of GBE on the metabolism and pharmacokinetics of clopidogrel. The in vitro study
using rat liver microsomes revealed that GBE significantly induced the conversion
of clopidogrel into its active metabolite. The effect of GBE on the
pharmacokinetics of clopidogrel was also investigated in vivo. Compared to rats
without GBE pretreatment, administration of 4 mg/kg, 20 mg/kg, and 100 mg/kg of
GBE significantly decreased the Cmax and the AUC0-infinity of clopidogrel in a
dose-dependent manner. As expected, pretreatment of high dose GBE significantly
increased the Cmax and AUC0-infinity of the clopidogrel active metabolite.
However, no marked change was observed following medium and low dose of GBE,
suggesting that the biotransformation of clopidogrel was altered differently by
high dose of GBE. Our study suggested that the awareness of the potential herb
drug interactions between GBE and clopidogrel should be increased in clinical
practice. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27487818
TI - Frequency-dependent selection: a diversifying force in microbial populations.
PMID- 27487817
TI - Negative frequency-dependent interactions can underlie phenotypic heterogeneity
in a clonal microbial population.
AB - Genetically identical cells in microbial populations often exhibit a remarkable
degree of phenotypic heterogeneity even in homogenous environments. Such
heterogeneity is commonly thought to represent a bet-hedging strategy against
environmental uncertainty. However, evolutionary game theory predicts that
phenotypic heterogeneity may also be a response to negative frequency-dependent
interactions that favor rare phenotypes over common ones. Here we provide
experimental evidence for this alternative explanation in the context of the well
studied yeast GAL network. In an environment containing the two sugars glucose
and galactose, the yeast GAL network displays stochastic bimodal activation. We
show that in this mixed sugar environment, GAL-ON and GAL-OFF phenotypes can each
invade the opposite phenotype when rare and that there exists a resulting stable
mix of phenotypes. Consistent with theoretical predictions, the resulting stable
mix of phenotypes is not necessarily optimal for population growth. We find that
the wild-type mixed strategist GAL network can invade populations of both pure
strategists while remaining uninvasible by either. Lastly, using laboratory
evolution we show that this mixed resource environment can directly drive the de
novo evolution of clonal phenotypic heterogeneity from a pure strategist
population. Taken together, our results provide experimental evidence that
negative frequency-dependent interactions can underlie the phenotypic
heterogeneity found in clonal microbial populations.
PMID- 27487819
TI - Heel ulcers do heal in patients with diabetes.
AB - A heel ulcer is considered to be a serious complication in patients with
diabetes, and there is limited information regarding outcome. In most of the
literature, a poor prognosis is described. The aim of this study was to
investigate a large cohort of ulcers located in the heel in patients with
diabetes. Seven hundred and sixty-eight patients [median age 73 (17-98)],
presenting with a heel ulcer at a multidisciplinary diabetes foot clinic,
fulfilled the inclusion criteria and were followed-up until final outcome. Fifty
eight per cent of the patients healed primarily; 7% healed after major
debridement; 9% healed after amputation and 25% died unhealed. Median healing
time was 17 weeks. Ulcer progression was seen in 19% of patients. Thirty-one
percent of patients had severe peripheral vascular disease. A creatinine level
below 91 umol/l was related to a higher probability for healing without major
debridement or amputation, whereas vascular surgery, nephropathy and oedema were
related to a lower probability for healing without major debridement or
amputation. Two thirds of heel ulcers do heal in patients with diabetes despite
patients being elderly and with extensive comorbidity. The extent of peripheral
vascular disease, nephropathy, oedema and decreased renal function are important
factors influencing outcome.
PMID- 27487820
TI - Surface expression of hippocampal NMDA GluN2B receptors regulated by fear
conditioning determines its contribution to memory consolidation in adult rats.
AB - The number and subtype composition of N-methyl-d-aspartate receptor (NMDAR) at
synapses determines their functional properties and role in learning and memory.
Genetically increased or decreased amount of GluN2B affects hippocampus-dependent
memory in the adult brain. But in some experimental conditions (e.g., memory
elicited by a single conditioning trial (1 CS-US)), GluN2B is not a necessary
factor, which indicates that the precise role of GluN2B in memory formation
requires further exploration. Here, we examined the role of GluN2B in the
consolidation of fear memory using two training paradigms. We found that GluN2B
was only required for the consolidation of memory elicited by five conditioning
trials (5 CS-US), not by 1 CS-US. Strikingly, the expression of membrane GluN2B
in CA1was training-strength-dependently increased after conditioning, and that
the amount of membrane GluN2B determined its involvement in memory consolidation.
Additionally, we demonstrated the increases in the activities of cAMP, ERK, and
CREB in the CA1 after conditioning, as well as the enhanced intrinsic
excitability and synaptic efficacy in CA1 neurons. Up-regulation of membrane
GluN2B contributed to these enhancements. These studies uncover a novel mechanism
for the involvement of GluN2B in memory consolidation by its accumulation at the
cell surface in response to behavioral training.
PMID- 27487821
TI - 2.4 A resolution crystal structure of human TRAP1NM, the Hsp90 paralog in the
mitochondrial matrix.
AB - TRAP1 is an organelle-specific Hsp90 paralog that is essential for neoplastic
growth. As a member of the Hsp90 family, TRAP1 is presumed to be a general
chaperone facilitating the late-stage folding of Hsp90 client proteins in the
mitochondrial matrix. Interestingly, TRAP1 cannot replace cytosolic Hsp90 in
protein folding, and none of the known Hsp90 co-chaperones are found in
mitochondria. Thus, the three-dimensional structure of TRAP1 must feature
regulatory elements that are essential to the ATPase activity and chaperone
function of TRAP1. Here, the crystal structure of a human TRAP1NM dimer is
presented, featuring an intact N-domain and M-domain structure, bound to
adenosine 5'-beta,gamma-imidotriphosphate (ADPNP). The crystal structure together
with epitope-mapping results shows that the TRAP1 M-domain loop 1 contacts the
neighboring subunit and forms a previously unobserved third dimer interface that
mediates the specific interaction with mitochondrial Hsp70.
PMID- 27487822
TI - Structural basis for the binding of succinate to succinyl-CoA synthetase.
AB - Succinyl-CoA synthetase catalyzes the only step in the citric acid cycle that
provides substrate-level phosphorylation. Although the binding sites for the
substrates CoA, phosphate, and the nucleotides ADP and ATP or GDP and GTP have
been identified, the binding site for succinate has not. To determine this
binding site, pig GTP-specific succinyl-CoA synthetase was crystallized in the
presence of succinate, magnesium ions and CoA, and the structure of the complex
was determined by X-ray crystallography to 2.2 A resolution. Succinate binds in
the carboxy-terminal domain of the beta-subunit. The succinate-binding site is
near both the active-site histidine residue that is phosphorylated in the
reaction and the free thiol of CoA. The carboxy-terminal domain rearranges when
succinate binds, burying this active site. However, succinate is not in position
for transfer of the phosphoryl group from phosphohistidine. Here, it is proposed
that when the active-site histidine residue has been phosphorylated by GTP, the
phosphohistidine displaces phosphate and triggers the movement of the carboxylate
of succinate into position to be phosphorylated. The structure shows why succinyl
CoA synthetase is specific for succinate and does not react appreciably with
citrate nor with the other C4-dicarboxylic acids of the citric acid cycle,
fumarate and oxaloacetate, but shows some activity with L-malate.
PMID- 27487823
TI - Crystal structure of the fluorescent protein from Dendronephthya sp. in both
green and photoconverted red forms.
AB - The fluorescent protein from Dendronephthya sp. (DendFP) is a member of the Kaede
like group of photoconvertible fluorescent proteins with a His62-Tyr63-Gly64
chromophore-forming sequence. Upon irradiation with UV and blue light, the
fluorescence of DendFP irreversibly changes from green (506 nm) to red (578 nm).
The photoconversion is accompanied by cleavage of the peptide backbone at the
C(alpha)-N bond of His62 and the formation of a terminal carboxamide group at the
preceding Leu61. The resulting double C(alpha)=C(beta) bond in His62 extends the
conjugation of the chromophore pi system to include imidazole, providing the red
fluorescence. Here, the three-dimensional structures of native green and
photoconverted red forms of DendFP determined at 1.81 and 2.14 A resolution,
respectively, are reported. This is the first structure of photoconverted red
DendFP to be reported to date. The structure-based mutagenesis of DendFP revealed
an important role of positions 142 and 193: replacement of the original Ser142
and His193 caused a moderate red shift in the fluorescence and a considerable
increase in the photoconversion rate. It was demonstrated that hydrogen bonding
of the chromophore to the Gln116 and Ser105 cluster is crucial for variation of
the photoconversion rate. The single replacement Gln116Asn disrupts the hydrogen
bonding of Gln116 to the chromophore, resulting in a 30-fold decrease in the
photoconversion rate, which was partially restored by a further Ser105Asn
replacement.
PMID- 27487824
TI - The 1.1 A resolution structure of a periplasmic phosphate-binding protein from
Stenotrophomonas maltophilia: a crystallization contaminant identified by
molecular replacement using the entire Protein Data Bank.
AB - During efforts to crystallize the enzyme 2,4-dihydroxyacetophenone dioxygenase
(DAD) from Alcaligenes sp. 4HAP, a small number of strongly diffracting protein
crystals were obtained after two years of crystal growth in one condition. The
crystals diffracted synchrotron radiation to almost 1.0 A resolution and were,
until recently, assumed to be formed by the DAD protein. However, when another
crystal form of this enzyme was eventually solved at lower resolution, molecular
replacement using this new structure as the search model did not give a
convincing solution with the original atomic resolution data set. Hence, it was
considered that these crystals might have arisen from a protein impurity,
although molecular replacement using the structures of common crystallization
contaminants as search models again failed. A script to perform molecular
replacement using MOLREP in which the first chain of every structure in the PDB
was used as a search model was run on a multi-core cluster. This identified a
number of prokaryotic phosphate-binding proteins as scoring highly in the MOLREP
peak lists. Calculation of an electron-density map at 1.1 A resolution based on
the solution obtained with PDB entry 2q9t allowed most of the amino acids to be
identified visually and built into the model. A BLAST search then indicated that
the molecule was most probably a phosphate-binding protein from Stenotrophomonas
maltophilia (UniProt ID B4SL31; gene ID Smal_2208), and fitting of the
corresponding sequence to the atomic resolution map fully corroborated this.
Proteins in this family have been linked to the virulence of antibiotic-resistant
strains of pathogenic bacteria and with biofilm formation. The structure of the
S. maltophilia protein has been refined to an R factor of 10.15% and an Rfree of
12.46% at 1.1 A resolution. The molecule adopts the type II periplasmic binding
protein (PBP) fold with a number of extensively elaborated loop regions. A fully
dehydrated phosphate anion is bound tightly between the two domains of the
protein and interacts with conserved residues and a number of helix dipoles.
PMID- 27487825
TI - Fixed target combined with spectral mapping: approaching 100% hit rates for
serial crystallography.
AB - The advent of ultrafast highly brilliant coherent X-ray free-electron laser
sources has driven the development of novel structure-determination approaches
for proteins, and promises visualization of protein dynamics on sub-picosecond
timescales with full atomic resolution. Significant efforts are being applied to
the development of sample-delivery systems that allow these unique sources to be
most efficiently exploited for high-throughput serial femtosecond
crystallography. Here, the next iteration of a fixed-target crystallography chip
designed for rapid and reliable delivery of up to 11 259 protein crystals with
high spatial precision is presented. An experimental scheme for predetermining
the positions of crystals in the chip by means of in situ spectroscopy using a
fiducial system for rapid, precise alignment and registration of the crystal
positions is presented. This delivers unprecedented performance in serial
crystallography experiments at room temperature under atmospheric pressure,
giving a raw hit rate approaching 100% with an effective indexing rate of
approximately 50%, increasing the efficiency of beam usage and allowing the
method to be applied to systems where the number of crystals is limited.
PMID- 27487826
TI - TakeTwo: an indexing algorithm suited to still images with known crystal
parameters.
AB - The indexing methods currently used for serial femtosecond crystallography were
originally developed for experiments in which crystals are rotated in the X-ray
beam, providing significant three-dimensional information. On the other hand,
shots from both X-ray free-electron lasers and serial synchrotron crystallography
experiments are still images, in which the few three-dimensional data available
arise only from the curvature of the Ewald sphere. Traditional synchrotron
crystallography methods are thus less well suited to still image data processing.
Here, a new indexing method is presented with the aim of maximizing information
use from a still image given the known unit-cell dimensions and space group.
Efficacy for cubic, hexagonal and orthorhombic space groups is shown, and for
those showing some evidence of diffraction the indexing rate ranged from 90%
(hexagonal space group) to 151% (cubic space group). Here, the indexing rate
refers to the number of lattices indexed per image.
PMID- 27487827
TI - RoboDiff: combining a sample changer and goniometer for highly automated
macromolecular crystallography experiments.
AB - Automation of the mounting of cryocooled samples is now a feature of the majority
of beamlines dedicated to macromolecular crystallography (MX). Robotic sample
changers have been developed over many years, with the latest designs increasing
capacity, reliability and speed. Here, the development of a new sample changer
deployed at the ESRF beamline MASSIF-1 (ID30A-1), based on an industrial six-axis
robot, is described. The device, named RoboDiff, includes a high-capacity dewar,
acts as both a sample changer and a high-accuracy goniometer, and has been
designed for completely unattended sample mounting and diffraction data
collection. This aim has been achieved using a high level of diagnostics at all
steps of the process from mounting and characterization to data collection. The
RoboDiff has been in service on the fully automated endstation MASSIF-1 at the
ESRF since September 2014 and, at the time of writing, has processed more than 20
000 samples completely automatically.
PMID- 27487828
TI - Structural basis for the extended substrate spectrum of AmpC BER and structure
guided discovery of the inhibition activity of citrate against the class C beta
lactamases AmpC BER and CMY-10.
AB - AmpC BER is an extended substrate spectrum class C beta-lactamase with a two
amino-acid insertion in the R2 loop compared with AmpC EC2. The crystal
structures of AmpC BER (S64A mutant) and AmpC EC2 were determined. Structural
comparison of the two proteins revealed that the insertion increases the
conformational flexibility of the R2 loop. Two citrate molecules originating from
the crystallization solution were observed in the active site of the S64A mutant.
One citrate molecule makes extensive interactions with active-site residues that
are highly conserved among class C beta-lactamases, whereas the other one is
weakly bound. Based on this structural observation, it is demonstrated that
citrate, a primary metabolite that is widely used as a food additive, is a
competitive inhibitor of two class C beta-lactamases (AmpC BER and CMY-10).
Consequently, the data indicate enhancement of the flexibility of the R2 loop as
an operative strategy for molecular evolution of extended-spectrum class C beta
lactamases, and also suggest that the citrate scaffold is recognized by the
active sites of class C beta-lactamases.
PMID- 27487829
TI - Progression of Metabolic Syndrome Severity During the Menopausal Transition.
AB - BACKGROUND: After menopause, women exhibit a higher prevalence of the metabolic
syndrome (MetS) and higher risk of cardiovascular disease. However, the timing of
changes in MetS severity over the menopausal transition and whether these changes
differ by racial/ethnic group remain unclear. METHODS AND RESULTS: We assessed
data from 1470 women from the Atherosclerosis Risk in Communities cohort who
experienced transition in menopausal status over 10 years (visits 1-4). We used
linear mixed models to evaluate changes by menopausal status (premenopause,
perimenopause, and postmenopause) in a MetS severity Z-score and in the
individual MetS components. While there were gradual increases in MetS severity
over time across menopause stages, black women in particular exhibited more rapid
progression in MetS severity during the premenopausal and perimenopausal periods
than during the postmenopausal period. In the postmenopausal period (compared
with prior periods), white women exhibited unfavorable decreases in high-density
lipoprotein, while black women exhibited favorable alterations in the rate of
change for waist circumference, triglycerides, high-density lipoprotein, and
glucose, contributing to the slowed progression of MetS severity. These changes
were all observed after adjusting for hormone replacement treatment. CONCLUSIONS:
During menopausal transition, women exhibited rapid increases in MetS severity
during the premenopausal and perimenopausal periods, with black women having
significant reductions in this increase in severity during the postmenopausal
period. These data suggest that the higher prevalence of MetS in postmenopausal
women may be caused more by changes during the menopausal transition than by
postmenopause. These findings may thus have implications regarding the timing of
cardiovascular risk relative to menopause.
PMID- 27487830
TI - The morphology of the adrenal gland in the European bison (Bison bonasus).
AB - BACKGROUND: The anatomy of the adrenal glands has been widely studied in many
species of domestic and wild mammals. However, there are no available literature
reports describing the morphology and morphometry of the adrenal glands of the
European bison (Bison bonasus). RESULTS: The study was conducted on 97 European
bison of both sexes. The growth of the adrenal glands corresponded to the growth
of the whole body, with the largest increase in size occurring in the first 2
years of the animal's life, followed by a slower increase in size until the
animal was 5-7 years old. There were no statistically significant differences
between ipsilateral adrenal glands of males and females with respect to age.
There was no statistically significant difference in weight between the left and
the right adrenal gland. However, there was a difference in the length, width and
thickness of the two glands. Reference intervals for adrenal gland size and
weight were computed separately for two bison age groups (up to 2 years of age
and older than two years). The adrenal gland consisted of a cortex and a medulla.
The connective-tissue capsule contained two layers. It had a fibrous structure
and abundant adipose tissue. The cortex was divided into three zones. The zona
glomerulosa contained cells arranged in bundles and curves. Numerous apoptotic
cells were observed among regular cells in the zona reticularis. There were
vacuoles in the cells of both zona fasciculata and zona reticularis, which formed
a foamy cytoplasm. The adrenal medulla was composed of large, dark cells with a
highly basophilic cytoplasm in the superficial region and of smaller, lighter
cells in deeper layers. Sinusoidal vessels were located in the central part of
the medulla. CONCLUSIONS: The left adrenal gland was significantly longer,
narrower and thinner than the right one. There were no significant differences in
the structure of the adrenal medulla and cortex of the European bison compared to
other species of domestic and wild mammals. There was a thick layer of adipose
cells at numerous locations in the adrenal capsule of the bison.
PMID- 27487831
TI - Human neuronal changes in brain edema and increased intracranial pressure.
AB - Functional and molecular changes associated with pathophysiological conditions
are relatively easily detected based on tissue samples collected from patients.
Population specific cellular responses to disease might remain undiscovered in
samples taken from organs formed by a multitude of cell types. This is
particularly apparent in the human cerebral cortex composed of a yet undefined
number of neuron types with a potentially different involvement in disease
processes. We combined cellular electrophysiology, anatomy and single cell
digital PCR in human neurons identified in situ for the first time to assess mRNA
expression and corresponding functional changes in response to edema and
increased intracranial pressure. In single pyramidal cells, mRNA copy numbers of
AQP1, AQP3, HMOX1, KCNN4, SCN3B and SOD2 increased, while CACNA1B, CRH decreased
in edema. In addition, single pyramidal cells increased the copy number of AQP1,
HTR5A and KCNS1 mRNAs in response to increased intracranial pressure. In contrast
to pyramidal cells, AQP1, HMOX1and KCNN4 remained unchanged in single cell
digital PCR performed on fast spiking cells in edema. Corroborating single cell
digital PCR results, pharmacological and immunohistochemical results also
suggested the presence of KCNN4 encoding the alpha-subunit of KCa3.1 channels in
edema on pyramidal cells, but not on interneurons. We measured the frequency of
spontaneous EPSPs on pyramidal cells in both pathophysiological conditions and on
fast spiking interneurons in edema and found a significant decrease in each case,
which was accompanied by an increase in input resistances on both cell types and
by a drop in dendritic spine density on pyramidal cells consistent with a loss of
excitatory synapses. Our results identify anatomical and/or physiological changes
in human pyramidal and fast spiking cells in edema and increased intracranial
pressure revealing cell type specific quantitative changes in gene expression.
Some of the edema/increased intracranial pressure modulated and single human
pyramidal cell verified gene products identified here might be considered as
novel pharmacological targets in cell type specific neuroprotection.
PMID- 27487832
TI - Evaluation of a quantitative measurement of suprapatellar effusion by
ultrasonography and its association with symptoms of radiographic knee
osteoarthritis: a cross-sectional observational study.
AB - BACKGROUND: Quantitative measurement of knee joint effusion by ultrasonography
has not been well established; however, a categorical measurement (e.g., a >=4-mm
deep suprapatellar pouch) is recommended. Therefore, the current study aimed to
elucidate the association between symptoms of knee osteoarthritis (OA) and the
quantitative measurement of suprapatellar effusion by ultrasonography. METHODS:
One hundred twenty-seven volunteers participated (31 men and 96 women; mean age:
68.3 +/- 9.8 years; body mass index: 23.2 +/- 3.0 kg/m(2)). The Kellgren-Lawrence
grades (KLGs) of both knees were assessed; all subjects had definitive
osteoarthritic change (KLG >=2) in both knee joints. Joint effusion was evaluated
using an ultrasound probe, which was placed longitudinally on the suprapatellar
pouch, and we determined the area (mm(2)) of the echo-free space. Then we summed
the effusion area of both knees. All subjects answered the knee injury and
osteoarthritis outcome scale (KOOS) questionnaire. Multiple linear regression
analysis was conducted to elucidate the association between the summed value of
the knee effusion area and the KOOS subscales, which were adjusted by age, sex,
body mass index, and KLG. RESULTS: Of 254 knees, 180 were KLG 2, 57 were KLG 3,
and 17 were KLG 4. The multiple regression models showed that the quantitative
knee effusion area significantly correlated with the following KOOS subscales:
pain (B = -0.057; beta = -0.253; P = 0.002), symptom (B = -0.053; beta = -0.251;
P = 0.002), sport and recreation (B = -0.069; beta = -0.205; P = 0.007), and
quality of life (B = -0.083; beta = -0.276; P = 0.001). CONCLUSION: In this cross
sectional study, the quantitative measurement of suprapatellar effusion by
ultrasonography was associated with symptoms of radiographic knee OA.
PMID- 27487833
TI - Towards human-controlled, real-time shape sensing based flexible needle steering
for MRI-guided percutaneous therapies.
AB - BACKGROUND: Accurate needle placement into soft tissue is essential to
percutaneous prostate cancer diagnosis and treatment procedures. METHODS: This
paper discusses the steering of a 20 gauge (G) FBG-integrated needle with three
sets of Fiber Bragg Grating (FBG) sensors. A fourth-order polynomial shape
reconstruction method is introduced and compared with previous approaches. To
control the needle, a bicycle model based navigation method is developed to
provide visual guidance lines for clinicians. A real-time model updating method
is proposed for needle steering inside inhomogeneous tissue. A series of
experiments were performed to evaluate the proposed needle shape reconstruction,
visual guidance and real-time model updating methods. RESULTS: Targeting
experiments were performed in soft plastic phantoms and in vitro tissues with
insertion depths ranging between 90 and 120 mm. Average targeting errors
calculated based upon the acquired camera images were 0.40 +/- 0.35 mm in
homogeneous plastic phantoms, 0.61 +/- 0.45 mm in multilayer plastic phantoms and
0.69 +/- 0.25 mm in ex vivo tissue. CONCLUSIONS: Results endorse the feasibility
and accuracy of the needle shape reconstruction and visual guidance methods
developed in this work. The approach implemented for the multilayer phantom study
could facilitate accurate needle placement efforts in real inhomogeneous tissues.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27487834
TI - The Changing Political Undercurrents in Health Services Delivery in Sub-Saharan
Africa.
AB - This article reviews the changing political undercurrent in health service
delivery in Sub-Saharan Africa, chronicling the ideological shift in orientation
toward neoliberalism in the health sector, an ideology crafted and introduced
into Sub-Saharan Africa by the International Monetary Fund and the World Bank.
The article examines the implication of this neoliberal reform on the efficiency
in health care provision and on the quality and accessibility of health services
by the poor and vulnerable. Drawing inference from countries like Nigeria, the
authors argue that the ascendency of neoliberalism in the health systems of Sub
Saharan Africa has engendered unethical practices and introduced elements of
moral hazard in the health sector, reducing the incentive for governments to
develop effective service delivery over the long term. The authors therefore
advocate for a rejection of neoliberal ideology in favor of a universal coverage
principle if an inclusive health system is to be developed.
PMID- 27487835
TI - The History and Future of Neoliberal Health Reform: Obamacare and Its
Predecessors.
AB - The Colombian reform of 1994, through a strange historical sequence, became a
model for health reform in Latin America, Europe, and the United States.
Officially, the reform aimed to improve access for the uninsured and
underinsured, in collaboration with the private, for-profit insurance industry.
After several historical attempts at health reform adhering to the neoliberal
pattern, favored by international financial institutions and multinational
insurance corporations, the Affordable Care Act (ACA) similarly enhanced access
by corporations to public-sector trust funds. An ideology favoring for-profit
corporations in the marketplace justified these reforms through unproven claims
about the efficiency of the private sector and enhanced quality of care under
principles of competition and business management. The ACA maintains this
historical continuity by dealing with health care as a commodity bought and sold
in a marketplace, rather than a fundamental human right to be guaranteed
according to principles of social solidarity. As the ACA heads toward probable
failure, a space finally will open for a U.S. national health program that does
not follow same historical patterns of the neoliberal model.
PMID- 27487836
TI - Health Promotion and Education: A Study of the Effectiveness of Programs Focusing
on the Aging Process.
AB - Considering the population aging and the failure of biologistic and hospital
based treatment model, health promotion programs based on scientific evidence are
necessary. A comprehensive review of literature was performed, aiming to identify
and analyze health promotion and education experiments focused on the aging
process. Papers published in eight databases, together with the database of the
Pan-American Health Organization, were selected based on review of titles and
abstracts, followed by a full text review conducted by two independent reviewers.
A total of 22 studies were included, the majority of which adopted a quantitative
approach, with a sample larger than 100 elderly or pre-retirement individuals.
The majority of studies reported positive results in terms of health promotion
and education. One study obtained minimum improvement and one reported that no
statistically significant improvement had occurred. The positive effects most
indicated by authors were: general or self-perceived improvement in physical
health, improvement in psychosocial aspects and in relation to the aging process,
improvement in adherence to preventative actions and in healthy conduct and
lifestyle, increase in level of physical activity, improvement in quality of life
and/or physical well-being, and improvement in activities of daily living or
reduction of the risk of developing disabilities.
PMID- 27487837
TI - Minimally invasive approach for percutaneous CentriMag right ventricular assist
device support using a single PROTEKDuo Cannula.
AB - BACKGROUND: Right ventricular failure is a serious complication after left
ventricular assist device placement. CASE PRESENTATION: A 70-year-old male in
decompensated heart failure with right ventricular failure after the placement of
a left ventricular assist device. A single dual-lumen PROTEKDuo cannula was
inserted percutaneously via the internal jugular vein to draw blood from the
right atrium and return into the pulmonary artery using the CentriMag system, by
passing the failing ventricle. The patient was successfully weaned from right
ventricular assist device. CONCLUSIONS: In comparison to two-cannula conventional
procedures, this right ventrivular assist device system improves patient
rehabilitation and minimizes blood loss and risk of infection, while shortening
procedure time and improving clinical outcomes in right ventricular failure.
PMID- 27487838
TI - Doxorubicin impairs cardiomyocyte viability by suppressing transcription factor
EB expression and disrupting autophagy.
AB - Doxorubicin (DOX) is an effective anti-cancer agent. However, DOX treatment
increases patient susceptibility to dilated cardiomyopathy. DOX predisposes
cardiomyocytes to insult by suppressing mitochondrial energy metabolism, altering
calcium flux, and disrupting proteolysis and proteostasis. Prior studies have
assessed the role of macroautophagy in DOX cardiotoxicity; however, limited
studies have examined whether DOX mediates cardiac injury through dysfunctions in
inter- and/or intra-lysosomal signaling events. Lysosomal signaling and function
is governed by transcription factor EB (TFEB). In the present study, we
hypothesized that DOX caused myocyte injury by impairing lysosomal function and
signaling through negative regulation of TFEB. Indeed, we found that DOX
repressed cellular TFEB expression, which was associated with impaired cathepsin
proteolytic activity across in vivo, ex vivo, and in vitro models of DOX
cardiotoxicity. Furthermore, we observed that loss of TFEB was associated with
reduction in macroautophagy protein expression, inhibition of autophagic flux,
impairments in lysosomal cathepsin B activity, and activation of cell death.
Restoration and/or activation of TFEB in DOX-treated cardiomyocytes prevented DOX
induced suppression of cathepsin B activity, reduced DOX-mediated reactive oxygen
species (ROS) overproduction, attenuated activation of caspase-3, and improved
cellular viability. Collectively, loss of TFEB inhibits lysosomal autophagy,
rendering cardiomyocytes susceptible to DOX-induced proteotoxicity and injury.
Our data reveal a novel mechanism wherein DOX primes cardiomyocytes for cell
death by depleting cellular TFEB.
PMID- 27487839
TI - Two independent evolutionary routes to Na+/H+ cotransport function in membrane
pyrophosphatases.
AB - Membrane-bound pyrophosphatases (mPPases) hydrolyze pyrophosphate (PPi) to
transport H(+), Na(+) or both and help organisms to cope with stress conditions,
such as high salinity or limiting nutrients. Recent elucidation of mPPase
structure and identification of subfamilies that have fully or partially switched
from Na(+) to H(+) pumping have established mPPases as versatile models for
studying the principles governing the mechanism, specificity and evolution of
cation transporters. In the present study, we constructed an accurate
phylogenetic map of the interface of Na(+)-transporting PPases (Na(+)-PPases) and
Na(+)- and H(+)-transporting PPases (Na(+),H(+)-PPases), which guided our
experimental exploration of the variations in PPi hydrolysis and ion transport
activities during evolution. Surprisingly, we identified two mPPase lineages that
independently acquired physiologically significant Na(+) and H(+) cotransport
function. Na(+),H(+)-PPases of the first lineage transport H(+) over an extended
[Na(+)] range, but progressively lose H(+) transport efficiency at high [Na(+)].
In contrast, H(+)-transport by Na(+),H(+)-PPases of the second lineage is not
inhibited by up to 100 mM Na(+) With the identification of Na(+),H(+)-PPase
subtypes, the mPPases protein superfamily appears as a continuum, ranging from
monospecific Na(+) transporters to transporters with tunable levels of Na(+) and
H(+) cotransport and further to monospecific H(+) transporters. Our results lend
credence to the concept that Na(+) and H(+) are transported by similar
mechanisms, allowing the relative efficiencies of Na(+) and H(+) transport to be
modulated by minor changes in protein structure during the course of adaptation
to a changing environment.
PMID- 27487840
TI - Phosphorylation of the dimeric cytoplasmic domain of the phytosulfokine receptor,
PSKR1.
AB - Phytosulfokines (PSKs) are plant peptide hormones that co-regulate plant growth,
differentiation and defense responses. PSKs signal through a plasma membrane
localized leucine-rich repeat receptor-like kinase (phytosulfokine receptor 1,
PSKR1) that also contains a functional cytosolic guanylate cyclase with its
cyclase catalytic center embedded within the kinase domain. To functionally
characterize this novel type of overlapping dual catalytic function, we
investigated the phosphorylation of PSKR1 in vitro Tandem mass spectrometry of
the cytoplasmic domain of PSKR1 (PSKR1cd) revealed at least 11 phosphorylation
sites (8 serines, 2 threonines and 1 tyrosine) within the PSKR1cd. Phosphomimetic
mutations of three serine residues (Ser686, Ser696 and Ser698) in tandem at the
juxta-membrane position resulted in enhanced kinase activity in the on-mutant
that was suppressed in the off-mutant, but both mutations reduced guanylate
cyclase activity. Both the on and off phosphomimetic mutations of the
phosphotyrosine (Tyr888) residue in the activation loop suppressed kinase
activity, while neither mutation affected guanylate cyclase activity. Size
exclusion and analytical ultracentrifugation analysis of the PSKR1cd suggest that
it is reversibly dimeric in solution, which was further confirmed by
biflourescence complementation. Taken together, these data suggest that in this
novel type of receptor domain architecture, specific phosphorylation and
dimerization are possibly essential mechanisms for ligand-mediated catalysis and
signaling.
PMID- 27487842
TI - An extension of generalized pairwise comparisons for prioritized outcomes in the
presence of censoring.
AB - Generalized pairwise comparisons have been proposed to permit a comprehensive
assessment of several prioritized outcomes between two groups of observations.
This procedure estimates Delta, the net chance of a better outcome with treatment
than with control by comparing the patients outcomes among all possible pairs
taking one patient from the treatment group and one patient from the control
group. For time to event outcomes, the standard procedure of generalized pairwise
comparisons is analogous to the Gehan's modification of the Mann-Whitney test
which is biased in presence of censored observation and less powerful than
Efron's modification of this test. We adapt Efron's modification to generalized
pairwise comparisons. We show how a pairwise contribution to Delta can be
calculated from the estimates of the survival function in the presence of right
censored data. We performed a simulation study to assess the bias, the type I
error and the power of the new procedure. The estimate of Delta with the new
procedure is only slightly biased even in presence of heavy censoring. We also
show how this bias can be corrected when only one time-to-event outcome is
analyzed. The new procedure has higher power in most cases compared to the
standard procedure.
PMID- 27487841
TI - Lactobacillus oligofermentans glucose, ribose and xylose transcriptomes show
higher similarity between glucose and xylose catabolism-induced responses in the
early exponential growth phase.
AB - BACKGROUND: Lactobacillus oligofermentans has been mostly isolated from cold
stored packaged meat products in connection with their spoilage, but its precise
role in meat spoilage is unknown. It belongs to the L. vaccinostercus group of
obligate heterofermentative lactobacilli that generally ferment pentoses (e.g.
xylose and ribose) more efficiently than hexoses (e.g. glucose). However, more
efficient hexose utilization can be induced. The regulation mechanisms of the
carbohydrate catabolism in such bacteria have been scarcely studied. To address
this question, we provided the complete genome sequence of L. oligofermentans LMG
22743(T) and generated time course transcriptomes during its growth on glucose,
ribose and xylose. RESULTS: The genome was manually annotated and its main
functional features were examined. L. oligofermentans was confirmed to be able to
efficiently utilize several hexoses and maltose, which is, presumably, induced by
its repeated cultivation with glucose in vitro. Unexpectedly, in the beginning of
the exponential growth phase, glucose- and xylose-induced transcriptome responses
were more similar, whereas toward the end of the growth phase xylose and ribose
transcriptomes became more alike. The promoter regions of genes simultaneously
upregulated both on glucose and xylose in comparison with ribose (particularly,
hexose and xylose utilization genes) were found to be enriched in the CcpA-
binding site. Transcriptionally, no glucose-induced carbon catabolite repression
was detected. The catabolism of glucose, which requires initial oxidation, led to
significant overexpression of the NAD(P)H re-oxidation genes, the upstream
regions of which were found to contain a motif, which was highly similar to a Rex
repressor binding site. CONCLUSIONS: This paper presents the second complete
genome and the first study of carbohydrate catabolism-dependent transcriptome
response for a member of the L. vaccinostercus group. The transcriptomic changes
detected in L. oligofermentans for growth with different carbohydrates differ
significantly from those of facultative heterofermentative lactobacilli. The
mechanism of CcpA regulation, putatively contributing to the observed
similarities between glucose- and xylose-induced transcriptome responses and the
absence of stringent carbon catabolite control, requires further studies.
Finally, the cell redox balance maintenance, in terms of the NAD(P)+/NAD(P)H
ratio, was predicted to be regulated by the Rex transcriptional regulator,
supporting the previously made inference of Rex-regulons for members of the
Lactobacillaceae family.
PMID- 27487843
TI - An overview of methods for network meta-analysis using individual participant
data: when do benefits arise?
AB - Network meta-analysis (NMA) is a common approach to summarizing relative
treatment effects from randomized trials with different treatment comparisons.
Most NMAs are based on published aggregate data (AD) and have limited
possibilities for investigating the extent of network consistency and between
study heterogeneity. Given that individual participant data (IPD) are considered
the gold standard in evidence synthesis, we explored statistical methods for IPD
NMA and investigated their potential advantages and limitations, compared with AD
NMA. We discuss several one-stage random-effects NMA models that account for
within-trial imbalances, treatment effect modifiers, missing response data and
longitudinal responses. We illustrate all models in a case study of 18
antidepressant trials with a continuous endpoint (the Hamilton Depression Score).
All trials suffered from drop-out; missingness of longitudinal responses ranged
from 21 to 41% after 6 weeks follow-up. Our results indicate that NMA based on
IPD may lead to increased precision of estimated treatment effects. Furthermore,
it can help to improve network consistency and explain between-study
heterogeneity by adjusting for participant-level effect modifiers and adopting
more advanced models for dealing with missing response data. We conclude that
implementation of IPD-NMA should be considered when trials are affected by
substantial drop-out rate, and when treatment effects are potentially influenced
by participant-level covariates.
PMID- 27487844
TI - Meta-analysis for the comparison of two diagnostic tests to a common gold
standard: A generalized linear mixed model approach.
AB - Meta-analysis of diagnostic studies is still a rapidly developing area of
biostatistical research. Especially, there is an increasing interest in methods
to compare different diagnostic tests to a common gold standard. Restricting to
the case of two diagnostic tests, in these meta-analyses the parameters of
interest are the differences of sensitivities and specificities (with their
corresponding confidence intervals) between the two diagnostic tests while
accounting for the various associations across single studies and between the two
tests. We propose statistical models with a quadrivariate response (where
sensitivity of test 1, specificity of test 1, sensitivity of test 2, and
specificity of test 2 are the four responses) as a sensible approach to this
task. Using a quadrivariate generalized linear mixed model naturally generalizes
the common standard bivariate model of meta-analysis for a single diagnostic
test. If information on several thresholds of the tests is available, the
quadrivariate model can be further generalized to yield a comparison of full
receiver operating characteristic (ROC) curves. We illustrate our model by an
example where two screening methods for the diagnosis of type 2 diabetes are
compared.
PMID- 27487845
TI - Hepatitis B infection awareness, vaccine perceptions and uptake, and serological
profile of a group of health care workers in Yaounde, Cameroon.
AB - BACKGROUND: Cameroon is one of the countries in Africa with the highest burden of
Hepatitis B infection. Health care workers are known to be at risk of
occupational exposure to blood and other infectious bodily fluids. The aim of
this study was to assess the profile of serological markers of hepatitis B virus
(HBV) infection, knowledge and perceptions regarding HBV infection among health
care workers in a health area in Yaounde. METHODS: A cross-sectional study was
conducted in the Mvog-Ada Health Area of the Djoungolo Health District from March
1 to November 31, 2014. All consenting health care workers were included in the
study. Serological markers of HBV (HBs Ag, Hbe Ag, anti-HBs Ab, anti-HBe Ab, anti
HBc Ab) were qualitatively tested using Biotech(r)(OneHBV-5 parameter rapid test
website) in each participant and the anti-HBs antibodies were quantified by ELISA
(Biorex) among those who were positive with the qualitative test. Chi square test
or its equivalents were used to compare qualitative variables and a p-value less
than or equal to 0.05 was considered significant. RESULT: A total of 100
participants were retained for the study out of 163 in the health area giving a
response rate of 61.34 %; the mean age was 30.5 (SD 6.8) years and 71 % of
participants were women. Forty seven percent (47 %) of workers had good level of
knowledge of HBV infection. The men were 3.20 times (95 % CI: 1.02-9.19, p =
0.04) more likely to have a good level of knowledge than women. Participants with
a university study level were more (95 % CI: 3.17-25, p < 0.0001) likely to have
a good level of knowledge than those with a high school study level. Ninety-six
percent of participants thought that they were at a greater risk of becoming
infected with HBV than the general population, 93 % felt that the vaccine should
be compulsory and all (100 %) were willing to recommend it to others. However,
only 19 % had received at least one dose of the vaccine. The proportion of HBs Ag
was 11 %. The different serological profiles with regard to HBV infection were
naive subjects (62 %), chronic carriers (11 %), vaccinated (19 %) and subjects
naturally immunized (8 %). Three out of the 19 participants who received at least
one dose of the vaccine, only 9 (47.4 %) of whom had titers >=100 IU/l indicating
a good response to vaccination. Among those who received three doses of the
vaccine (n = 12, 63 %), 2 (16, 66 %) had poor response to vaccination (HBs Ab
titers < 100 IU/l). CONCLUSION: The prevalence of HBs Ag among health care
workers in the Mvog-Ada Health Area is high (11 %). These workers are at high
risk of HBV infection because of very low vaccine uptake and poor post-exposure
practices. Their knowledge of HBV infection is non-optimal.
PMID- 27487846
TI - Nuclear internal transcribed spacer-1 as a sensitive genetic marker for
environmental DNA studies in common carp Cyprinus carpio.
AB - The recently developed environmental DNA (eDNA) analysis has been used to
estimate the distribution of aquatic vertebrates by using mitochondrial DNA
(mtDNA) as a genetic marker. However, mtDNA markers have certain drawbacks such
as variable copy number and maternal inheritance. In this study, we investigated
the potential of using nuclear DNA (ncDNA) as a more reliable genetic marker for
eDNA analysis by using common carp (Cyprinus carpio). We measured the copy
numbers of cytochrome b (CytB) gene region of mtDNA and internal transcribed
spacer 1 (ITS1) region of ribosomal DNA of ncDNA in various carp tissues and then
compared the detectability of these markers in eDNA samples. In the DNA extracted
from the brain and gill tissues and intestinal contents, CytB was detected at
95.1 +/- 10.7 (mean +/- 1 standard error), 29.7 +/- 1.59 and 24.0 +/- 4.33 copies
per cell, respectively, and ITS1 was detected at 1760 +/- 343, 2880 +/- 503 and
1910 +/- 352 copies per cell, respectively. In the eDNA samples from mesocosm,
pond and lake water, the copy numbers of ITS1 were about 160, 300 and 150 times
higher than those of CytB, respectively. The minimum volume of pond water
required for quantification was 33 and 100 mL for ITS1 and CytB, respectively.
These results suggested that ITS1 is a more sensitive genetic marker for eDNA
studies of C. carpio.
PMID- 27487847
TI - Left-sided pancreatic incidentalomas treated with laparoscopic approach: a report
of 20 cases.
AB - BACKGROUND: The diffusion of cross-sectional imaging has recently permitted the
detection of an increasing number of incidentalomas localized in the distal
pancreas. Currently, there are no studies in the literature exploring the
laparoscopic approach as treatment for left-sided pancreatic incidentalomas.
METHODS AND RESULTS: We report a series of 20 incidentalomas localized in the
body and tail of the pancreas treated with laparoscopic surgery over the period
2010-2014. The incidental masses of our series included a great variety of
histotypes and a relevant proportion of malignant lesions. In two cases, the
laparoscopic procedures were converted to open surgery. No postoperative death
was observed. The postoperative pancreatic fistula rate was 20 %, and the new
onset diabetes rate was 25 %. CONCLUSIONS: Left-sided pancreatic incidentalomas
in patients with minor comorbidities can be safely treated with laparoscopic
approach. Only clinical trials will confirm whether laparoscopic surgery is an
effective treatment for malignant lesions.
PMID- 27487848
TI - Determination of knowledge levels, attitude and behaviors of female university
students concerning cervical cancer, human papiloma virus and its vaccine.
AB - BACKGROUND: The purpose of the study is to investigate knowledge, attitudes and
behaviours concerning cervical cancer, HPV and HPV vaccine of female students
studying at a university in a health related department and explore variables
affecting taking the vaccine. METHODS: The research group consists of female
students attending a health related department in Balikesir University. The data
of this cross-sectional research was collected via surveys. RESULTS: The average
total knowledge score of the students concerning risks, symptoms and screening
methods of cervical cancer and HPV vaccines was 14.15 +/- 6.7. The HPV knowledge
score of the students attending the faculty of medicine was higher compared to
the students attending other departments and their HPV vaccine knowledge score
was higher compared to the students attending nursing and paramedics students.
The HPV vaccine knowledge score of the students attending the department of
midwifery was significantly higher compared to other students. Only 0.9 % of the
students took the vaccine. One third of the students who did not take the vaccine
did not know that the vaccine was available in our country. In terms of the
department that they attended, the students with a higher total knowledge score
compared to the average (OR:1.5) and students with history of cancer in their
families (OR:1.6) were more likely to consider taking the vaccine. CONCLUSIONS:
Research group's knowledge on risk factors of cervical cancer, Pap smear test,
symptoms and prevention ways of cancer, HPV and HPV vaccine was low.
PMID- 27487849
TI - Nutritional assessment and post-procedural complications in older stroke patients
after insertion of percutaneous endoscopic gastrostomy - a retrospective study.
AB - BACKGROUND: Oropharyngeal dysphagia is one of the major complications of stroke
and a risk factor for malnutrition and prolonged in-hospital stay. OBJECTIVE: The
overall aim was to describe to what extent nutritional assessments (i.e. BMI
kg/m(2), eating problem, and weight loss) were performed and documented in the
records of older stroke patients treated with enteral nutrition by percutaneous
endoscopic gastrostomy (PEG). A secondary aim was to identify documented post
procedural complications after PEG insertion during hospital stay. DESIGN: The
study is retrospective. Data were collected from records of 161 stroke patients
>=65 years, who received PEG, admitted to three stroke units during a 4-year
period. RESULTS: Mean age of the patients was 82.2 (+/-7) years, and 86% of the
patients were >=75 years old. On admission, body weight was documented in 50% of
the patients and at discharge in 38% of the patients. BMI data were not
documented at all at discharge in one of the units. Almost 80% of the patients
fulfilled the European Network criteria for multimorbidity. Morbidity and
multimorbidity correlated to the length of stay (p<0.0005). Complications were
reported in 111 (69%) of the patient records. In 53 patients (33%) more than one
complication was reported. A total of 116 pressure ulcers were reported and 30
patients had more than one pressure ulcer. The number of complications was
related to weight loss (p=0.046) and BMI change (p=0.018). CONCLUSIONS: Essential
information of the patient's nutritional status was poorly recorded which could
affect the patient's nutritional treatment during the hospital stay. This study
indicates that implementation of guidelines in patients with stroke is needed.
The high number of pressure ulcers was an unexpected finding.
PMID- 27487850
TI - Low-molecular-weight fucoidan and high-stability fucoxanthin from brown seaweed
exert prebiotics and anti-inflammatory activities in Caco-2 cells.
AB - BACKGROUND: The aim of this study is to investigate the anti-inflammatory effects
of low-molecular-weight fucoidan (LMF) and high-stability fucoxanthin (HS-Fucox)
in a lipopolysaccharide-induced inflammatory Caco-2 cell line co-culture with B.
lactis. METHODS: We used various methods such as transepithelial resistance (TER)
assay, cytokine secretion assay, and tight junction protein mRNA expression assay
to examine LMF and HS-Fucox anti-inflammatory properties. RESULTS: LMF and HS
Fucox activated probiotic growth and reduced the inflammation of the intestinal
epithelial cells. Moreover, the combination of LMFHS-Fucox dramatically enhanced
the intestinal epithelial barrier and immune function against the
lipopolysaccharide effect by inhibiting IL-1beta and TNF-alpha and promoting IL
10 and IFN-gamma. CONCLUSION: These findings suggested that LMF and HS-Fucox,
alone or in combination, could be the potential natural compounds to enhance the
immune system and have an anti-inflammatory effect on the intestinal cells.
PMID- 27487851
TI - Human Fetuin-A Rs4918 Polymorphism and its Association with Obesity in Healthy
Persons and in Patients with Myocardial Infarction in Two Hungarian Cohorts.
AB - BACKGROUND Human fetuin A (AHSG) has been associated with the development of
obesity, insulin resistance, type 2 diabetes mellitus, and atherosclerosis.
Observations on the role of AHSG rs4918 single-nucleotide polymorphism are
contradictory. We investigated the association between variants of rs4918 and
parameters of obesity, lipid status, tumor necrosis factor-alpha (TNFalpha),
adipokines (adiponectin, resistin, leptin), and insulin resistance in healthy
persons and in patients with previous myocardial infarction. MATERIAL AND METHODS
This was a cross-sectional study comprising cohort 1 (81 healthy individuals) and
cohort 2 (157 patients with previous myocardial infarction). We used the allele
specific KASP genotyping assay to detect rs4918 polymorphism. RESULTS In cohort
1, G-nucleotide carriers had significantly lower serum TNFalpha, adiponectin, and
higher leptin concentrations than in non-G carriers. These differences, however,
were not observed in cohort 2. In cohort 2, G-carriers had lower BMI and waist
circumferences than in non-G carriers. The G allele was more frequent among lean
than obese patients (RR=1.067, 95%CI=1.053-2.651, p=0.015). An association
between BMI and rs4918 polymorphism was observed among patients without diabetes
(CC/CG/GG genotypes: p=0.003, G vs. non-G allele: p=0.008) but not in diabetics.
In addition, a strong linearity between BMI and the CC/CG/GG genotypes
(association value: 4.416, p=0.036) and the frequency of the G allele (7.420,
p=0.006) could be identified. In cohort 2, non-obese, non-diabetic G-carriers
still had lower BMI and waist circumferences than in non-G carriers. CONCLUSIONS
The rs4918 minor variant is associated with lower TNFalpha and adiponectin,
higher leptin levels in healthy persons, and more favorable anthropomorphic
parameters of obesity in cohort 2.
PMID- 27487853
TI - Ocular complications in HIV positive patients on antiretroviral therapy in Ghana.
AB - BACKGROUND: Patients infected with human immunodeficiency virus (HIV) usually
develop some form of ocular complication in the different segments of the eye due
to immune deficiency. In Ghana, data regarding ocular complications among
HIV/AIDS patients is scarce. This study investigated the occurrence of ocular
complications in HIV infected patients undergoing antiretroviral therapy at the
Agogo Presbyterian Hospital in the Ashanti Region of Ghana. METHODS: Blood
samples were taken from 100 confirmed HIV infected patients. The CD4 + T cell
count and WHO clinical staging were determined. The patients were taken through
thorough ophthalmic assessments to determine any ocular complications. RESULTS:
Forty-eight patients (48 %) had at least one HIV-related ocular complication.
These complications occurred more frequently among those with CD4 counts below
200 cells/MUL. Of the participants with HIV-related ocular complications, 11 (23
%) had retinal microvasculopathy, 10 (21 %) showed allergic conjunctivitis, 7 (15
%) had HIV retinopathy and 7 (15 %) had conjunctival carcinoma. All the
participants in the study were on first-line antiretroviral therapy; 68 % were
females and 72 % were in the Stage 3 of the WHO Clinical Staging of HIV
infection. CONCLUSION: The prevalence of ocular complications in HIV positive
persons under treatment in Ghana is high. Lower CD4 + T cell counts coupled with
age were predisposing factors to HIV-related ocular complications.
PMID- 27487852
TI - The use of digital PCR to improve the application of quantitative molecular
diagnostic methods for tuberculosis.
AB - BACKGROUND: Real-time PCR (qPCR) based methods, such as the Xpert MTB/RIF, are
increasingly being used to diagnose tuberculosis (TB). While qualitative methods
are adequate for diagnosis, the therapeutic monitoring of TB patients requires
quantitative methods currently performed using smear microscopy. The potential
use of quantitative molecular measurements for therapeutic monitoring has been
investigated but findings have been variable and inconclusive. The lack of an
adequate reference method and reference materials is a barrier to understanding
the source of such disagreement. Digital PCR (dPCR) offers the potential for an
accurate method for quantification of specific DNA sequences in reference
materials which can be used to evaluate quantitative molecular methods for TB
treatment monitoring. METHODS: To assess a novel approach for the development of
quality assurance materials we used dPCR to quantify specific DNA sequences in a
range of prototype reference materials and evaluated accuracy between different
laboratories and instruments. The materials were then also used to evaluate the
quantitative performance of qPCR and Xpert MTB/RIF in eight clinical testing
laboratories. RESULTS: dPCR was found to provide results in good agreement with
the other methods tested and to be highly reproducible between laboratories
without calibration even when using different instruments. When the reference
materials were analysed with qPCR and Xpert MTB/RIF by clinical laboratories, all
laboratories were able to correctly rank the reference materials according to
concentration, however there was a marked difference in the measured magnitude.
CONCLUSIONS: TB is a disease where the quantification of the pathogen could lead
to better patient management and qPCR methods offer the potential to rapidly
perform such analysis. However, our findings suggest that when precisely
characterised materials are used to evaluate qPCR methods, the measurement result
variation is too high to determine whether molecular quantification of
Mycobacterium tuberculosis would provide a clinically useful readout. The methods
described in this study provide a means by which the technical performance of
quantitative molecular methods can be evaluated independently of clinical
variability to improve accuracy of measurement results. These will assist in
ultimately increasing the likelihood that such approaches could be used to
improve patient management of TB.
PMID- 27487854
TI - Risk Factors for Stroke among Young-Old and Old-Old Community-Dwelling Adults in
Japan: The Ohasama Study.
AB - AIM: Few studies have addressed stroke risk factors in older populations,
particularly among the old-old. We examined differences in traditional risk
factors for stroke among the old-old compared with the young-old in community
dwelling Japanese adults. METHODS: We followed 2,065 residents aged >= 60 years
who had no history of stroke. Traditional risk factors for stroke were obtained
from a self-administered questionnaire at baseline. We classified participants
into two age categories, 60-74 years (n=1,502) and >= 75 years (n=563), and
assessed whether traditional risk factors were differentially associated with
stroke incidence according to age category. Hazard ratios were calculated by the
Cox proportional hazards model, adjusting for confounding factors and competing
risk of death. RESULTS: During a median follow-up of 12.8 and 7.9 years, 163 and
111 participants aged 60-74 and >= 75 years, respectively, developed a first
stroke. Hypertension was consistently associated with increased risk of stroke,
regardless of age category. Diabetes mellitus was associated with increased risk
of stroke in those aged 60-74 years (hazard ratio, 1.50; 95% confidence interval,
1.00-2.25), but not in those aged >= 75 years (hazard ratio, 0.65; 95% confidence
interval, 0.33-1.29), with significant interaction by age (P=0.035). No
traditional risk factor other than hypertension was associated with stroke among
those aged >= 75 years. CONCLUSION: Those with hypertension had significantly
higher stroke risk among old people, while diabetes mellitus was differentially
associated with stroke according to age category. Our findings indicate the
importance of different prevention strategies for stroke incidence according to
age category.
PMID- 27487855
TI - Commentary: Stabilizing Constructs through Collaboration across Different
Research Fields as a Way to Foster the Integrative Approach of the Research
Domain Criteria (RDoC) Project.
PMID- 27487856
TI - XPO1, therapeutic ... and prognostic target in sarcomas.
PMID- 27487857
TI - Role of monocytes and endothelial cells in heparin-induced thrombocytopenia.
AB - Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder characterised by
thrombocytopenia and thrombosis. The mechanisms leading to platelet destruction
are complex and the thrombotic complications of HIT appear to be due to multiple
different intravascular targets. The dual binding of HIT antibodies to platelet
surface PF4/GAG complexes and to FcgammaRIIA likely leads to both platelet
clearance and to their direct activation. Monocytes and endothelial cells bind
PF4 with higher avidity than platelets and are more resistant to competitive
removal of surface-bound PF4 in the presence of heparin. Binding of HIT
antibodies to PF4/glycosaminoglycan complexes on the surface on these cells leads
to their activation and increased procoagulant activity. Binding of higher levels
of PF4 released from activated platelets to the endothelium may lead to changes
of the anticoagulant properties of the glycocalyx and target the endothelial
cells for HIT antibodies. Pathogenic antibodies bound to endothelial cells
further promote prothrombotic conditions by a mechanism that is independent of
FcgammaR activation, yet not completely understood. A more detailed understanding
of the role of monocytes and endothelium may identify new targets for
intervention to mitigate the risk of thrombosis with less impact on systemic
haemostasis than current approaches to treatment for this serious disorder.
PMID- 27487858
TI - Biologic modulation in renal regeneration.
AB - INTRODUCTION: Chronic kidney disease (CKD) is recognized as a health care problem
of increasing importance. Following the discovery of renal progenitors, the
investigation of new therapeutic approaches to promote the kidney regenerative
capacity has received increasing research attention. AREAS COVERED: The authors
discuss the current knowledge of glomerular regeneration by renal progenitors and
the modulation of their behavior through chemical and biological agents. The
regenerative capacity of renal progenitors after injury must be regulated in
order to prevent an inefficient or excessive response that could lead to a failed
attempt to replace lost podocytes. In addition, they discuss the most relevant
pathways involved in tubular repair and how these could be modulated in order to
obtain renal regeneration rather than progression of a fibrotic maladaptive
response. EXPERT OPINION: Modulation of the endogenous renal regenerative
capacity is a new approach in the treatment of kidney diseases. Research efforts
that concentrate on the potential regenerative capacity of the kidney can be
advantageous when the experimental results are translated into clinical practice
and may open the way to new therapeutic strategies for CKD.
PMID- 27487859
TI - Pharmacological and toxicological assessment of innovative self-assembled
polymeric micelles as powders for insulin pulmonary delivery.
AB - AIM: Explore the use of polymeric micelles in the development of powders intended
for pulmonary delivery of biopharmaceuticals, using insulin as a model protein.
MATERIALS & METHODS: Formulations were assessed in vitro for aerosolization
properties and in vivo for efficacy and safety using a streptozotocin-induced
diabetic rat model. RESULTS: Powders presented good aerosolization properties
like fine particle fraction superior to 40% and a mass median aerodynamic
diameter inferior of 6 MUm. Endotracheally instilled powders have shown a faster
onset of action than subcutaneous administration of insulin at a dose of 10
IU/kg, with pharmacological availabilities up to 32.5% of those achieved by
subcutaneous route. Additionally, micelles improved the hypoglycemic effect of
insulin. Bronchoalveolar lavage screening for toxicity markers (e.g., lactate
dehydrogenase, cytokines) revealed no signs of lung inflammation and cytotoxicity
14 days postadministration. CONCLUSION: Developed powders showed promising safety
and efficacy characteristics for the systemic delivery of insulin by pulmonary
administration.
PMID- 27487860
TI - Psoriatic arthritis: lessons from imaging studies and implications for therapy.
AB - INTRODUCTION: Modern imaging may aid in the diagnosis, prognosis and monitoring
of therapeutic response in psoriatic arthritis (PsA). Detection of osteitis and
technical advances like whole body magnetic resonance imaging (MRI) exemplify the
value of this technology. Areas covered: Ultrasound (US) provides a clinic-based
tool for evaluating both joint pathologies and extra-articular structures
(especially enthesitis) including skin and nail disease. Recent studies have
demonstrated subclinical disease in psoriasis without arthritis, as well as in
PsA, with implications for diagnosis and treatment classification. Modern imaging
can also facilitate decisions on tapering of expensive biologics, though real
world clinical studies are still lacking. Expert commentary: The increase in
novel PsA therapies should increase the utilization of modern imaging, providing
both increased validation of imaging biomarkers as well as responsive outcome
measures.
PMID- 27487861
TI - A new template for referees and guidance on writing high quality papers.
PMID- 27487862
TI - Photon radiotherapy has reached its limit in terms of catching up dosimetrically
with proton therapy.
PMID- 27487863
TI - Robert O. Gorson, M.S.
PMID- 27487864
TI - Noninvasive microwave ablation zone radii estimation using x-ray CT image
analysis.
AB - PURPOSE: The aims of this study were to noninvasively and automatically estimate
both the radius of the ablated liver tissue and the radius encircling the treated
zone, which also defines where the tissue is definitely untreated during a
microwave (MW) thermal ablation procedure. METHODS: Fourteen ex vivo bovine fresh
liver specimens were ablated at 40 W using a 14 G microwave antenna, for
durations of 3, 6, 8, and 10 min. The tissues were scanned every 5 s during the
ablation using an x-ray CT scanner. In order to estimate the radius of the
ablation zone, the acquired images were transformed into a polar presentation by
displaying the Hounsfield units (HU) as a function of angle and radius. From this
polar presentation, the average HU radial profile was analyzed at each time point
and the ablation zone radius was estimated. In addition, textural analysis was
applied to the original CT images. The proposed algorithm identified high entropy
regions and estimated the treated zone radius per time. The estimated ablated
zone radii as a function of treatment durations were compared, by means of
correlation coefficient and root mean square error (RMSE) to gross pathology
measurements taken immediately post-treatment from similarly ablated tissue.
RESULTS: Both the estimated ablation radii and the treated zone radii
demonstrated strong correlation with the measured gross pathology values (R(2) >=
0.89 and R(2) >= 0.86, respectively). The automated ablation radii estimation had
an average discrepancy of less than 1 mm (RMSE = 0.65 mm) from the gross
pathology measured values, while the treated zone radii showed a slight
overestimation of approximately 1.5 mm (RMSE = 1.6 mm). CONCLUSIONS: Noninvasive
monitoring of MW ablation using x-ray CT and image analysis is feasible.
Automatic estimations of the ablation zone radius and the radius encompassing the
treated zone that highly correlate with actual ablation measured values can be
obtained. This technique can therefore potentially be used to obtain real time
monitoring and improve the clinical outcome.
PMID- 27487865
TI - Generic and robust method for automatic segmentation of PET images using an
active contour model.
AB - PURPOSE: Although positron emission tomography (PET) images have shown potential
to improve the accuracy of targeting in radiation therapy planning and assessment
of response to treatment, the boundaries of tumors are not easily distinguishable
from surrounding normal tissue owing to the low spatial resolution and inherent
noisy characteristics of PET images. The objective of this study is to develop a
generic and robust method for automatic delineation of tumor volumes using an
active contour model and to evaluate its performance using phantom and clinical
studies. METHODS: MASAC, a method for automatic segmentation using an active
contour model, incorporates the histogram fuzzy C-means clustering, and localized
and textural information to constrain the active contour to detect boundaries in
an accurate and robust manner. Moreover, the lattice Boltzmann method is used as
an alternative approach for solving the level set equation to make it faster and
suitable for parallel programming. Twenty simulated phantom studies and 16
clinical studies, including six cases of pharyngolaryngeal squamous cell
carcinoma and ten cases of nonsmall cell lung cancer, were included to evaluate
its performance. Besides, the proposed method was also compared with the
contourlet-based active contour algorithm (CAC) and Schaefer's thresholding
method (ST). The relative volume error (RE), Dice similarity coefficient (DSC),
and classification error (CE) metrics were used to analyze the results
quantitatively. RESULTS: For the simulated phantom studies (PSs), MASAC and CAC
provide similar segmentations of the different lesions, while ST fails to achieve
reliable results. For the clinical datasets (2 cases with connected high-uptake
regions excluded) (CSs), CAC provides for the lowest mean RE (-8.38% +/- 27.49%),
while MASAC achieves the best mean DSC (0.71 +/- 0.09) and mean CE (53.92% +/-
12.65%), respectively. MASAC could reliably quantify different types of lesions
assessed in this work with good accuracy, resulting in a mean RE of -13.35% +/-
11.87% and -11.15% +/- 23.66%, a mean DSC of 0.89 +/- 0.05 and 0.71 +/- 0.09, and
a mean CE of 19.19% +/- 7.89% and 53.92% +/- 12.65%, for PSs and CSs,
respectively. CONCLUSIONS: The authors' results demonstrate that the developed
novel PET segmentation algorithm is applicable to various types of lesions in the
authors' study and is capable of producing accurate and consistent target volume
delineations, potentially resulting in reduced intraobserver and interobserver
variabilities observed when using manual delineation and improved accuracy in
treatment planning and outcome evaluation.
PMID- 27487866
TI - Impact of bowtie filter and object position on the two-dimensional noise power
spectrum of a clinical MDCT system.
AB - PURPOSE: Noise characteristics of clinical multidetector CT (MDCT) systems can be
quantified by the noise power spectrum (NPS). Although the NPS of CT has been
extensively studied in the past few decades, the joint impact of the bowtie
filter and object position on the NPS has not been systematically investigated.
This work studies the interplay of these two factors on the two dimensional (2D)
local NPS of a clinical CT system that uses the filtered backprojection algorithm
for image reconstruction. METHODS: A generalized NPS model was developed to
account for the impact of the bowtie filter and image object location in the scan
field-of-view (SFOV). For a given bowtie filter, image object, and its location
in the SFOV, the shape and rotational symmetries of the 2D local NPS were
directly computed from the NPS model without going through the image
reconstruction process. The obtained NPS was then compared with the measured NPSs
from the reconstructed noise-only CT images in both numerical phantom simulation
studies and experimental phantom studies using a clinical MDCT scanner. The shape
and the associated symmetry of the 2D NPS were classified by borrowing the well
known atomic spectral symbols s, p, and d, which correspond to circular,
dumbbell, and cloverleaf symmetries, respectively, of the wave function of
electrons in an atom. Finally, simulated bar patterns were embedded into
experimentally acquired noise backgrounds to demonstrate the impact of different
NPS symmetries on the visual perception of the object. RESULTS: (1) For a central
region in a centered cylindrical object, an s-wave symmetry was always present in
the NPS, no matter whether the bowtie filter was present or not. In contrast, for
a peripheral region in a centered object, the symmetry of its NPS was highly
dependent on the bowtie filter, and both p-wave symmetry and d-wave symmetry were
observed in the NPS. (2) For a centered region-ofinterest (ROI) in an off
centered object, the symmetry of its NPS was found to be different from that of a
peripheral ROI in the centered object, even when the physical positions of the
two ROIs relative to the isocenter were the same. (3) The potential clinical
impact of the highly anisotropic NPS, caused by the interplay of the bowtie
filter and position of the image object, was highlighted in images of specific
bar patterns oriented at different angles. The visual perception of the bar
patterns was found to be strongly dependent on their orientation. CONCLUSIONS:
The NPS of CT depends strongly on the bowtie filter and object position. Even if
the location of the ROI with respect to the isocenter is fixed, there can be
different symmetries in the NPS, which depend on the object position and the size
of the bowtie filter. For an isolated off-centered object, the NPS of its CT
images cannot be represented by the NPS measured from a centered object.
PMID- 27487867
TI - Technical Note: On the impact of the incident electron beam energy on the primary
dose component of flattening filter free photon beams.
AB - PURPOSE: For commercially available linear accelerators (Linacs), the electron
energies of flattening filter free (FFF) and flattened (FF) beams are either
identical or the electron energy of the FFF beam is increased to match the
percentage depth dose curve (PDD) of the FF beam (in reference geometry). This
study focuses on the primary dose components of FFF beams for both kinds of
settings, studied on the same Linac. METHODS: The measurements were conducted on
a VersaHD Linac (Elekta, Crawley, UK) for both FF and FFF beams with nominal
energies of 6 and 10 MV. In the clinical setting of the VersaHD, the energy of
FFFM (Matched) beams is set to match the PDDs of the FF beams. In contrast the
incident electron beam of the FFFU beam was set to the same energy as for the FF
beam. Half value layers (HVLs) and a dual parameter beam quality specifier
(DPBQS) were determined. RESULTS: For the 6 MV FFFM beam, HVL and DPBQS values
were very similar compared to those of the 6 MV FF beam, while for the 10 MV FFFM
and FF beams, only %dd(10)x and HVL values were comparable (differences below
1.5%). This shows that matching the PDD at one depth does not guarantee other
beam quality dependent parameters to be matched. For FFFU beams, all investigated
beam quality specifiers were significantly different compared to those for FF
beams of the same nominal accelerator potential. The DPBQS of the 6 MV FF and
FFFM beams was equal within the measurement uncertainty and was comparable to
published data of a machine with similar TPR20,10 and %dd(10)x. In contrast to
that, the DPBQS's two parameters of the 10 MV FFFM beam were substantially higher
compared to those for the 10 MV FF beam. CONCLUSIONS: PDD-matched FF and FFF
beams of both nominal accelerator potentials were observed to have similar HVL
values, indicating similarity of their primary dose components. Using the DPBQS
revealed that the mean attenuation coefficient was found to be the same within
the uncertainty of 0.8% for 6 MV FF and 6 MV FFFM beams, while for 10 MV beams,
they differed by 6.4%. This shows that the DPBQS can provide a differentiation of
photon beam characteristics that would remain hidden by the use of a single beam
quality specifier, such as %dd(10)x or HVL.
PMID- 27487868
TI - Technical Note: Dosimetric effects of couch position variability on treatment
plan quality with an MRI-guided Co-60 radiation therapy machine.
AB - PURPOSE: Magnetic resonance imaging (MRI) guidance in radiation therapy brings
real-time imaging and adaptive planning into the treatment vault where it can
account for interfraction and intrafraction movement of soft tissue. The only
commercially available MRI-guided radiation therapy device is a three-head (60)Co
and MRI system with an integrated treatment planning system (TPS). Couch
attenuation of the beam of up to 20% is well modeled in the TPS. Variations in
the patient's day-to-day position introduce discrepancies in the actual couch
attenuation as modeled in the treatment plan. For this reason, the authors'
institution avoids plans with beams that pass through or near the couch edges.
This study investigates the effects of differential beam attenuation by the couch
due to couch shifts in order to determine whether couch edge avoidance
restrictions can be lifted. Couch shifts were simulated using a Monte Carlo
treatment planning system and ion chamber measurements performed for validation.
METHODS: A total of 27 plans from 23 patients were investigated. Couch shifts of
1 and 2 cm were introduced in combinations of lateral and vertical directions to
simulate patient position variations giving 16 shifted plans per reference plan.
The 1 and 2 cm shifts were based on shifts recorded in 320 treatment fractions.
RESULTS: Following TG176 recommendations for measurement methods, couch
attenuation measurements agreed with TPS modeled attenuation to within 2.1%.
Planning target volume D95 changed less than 1% for 1 and 2 cm couch shifts in
only the x-direction and less than 3% for all directions. CONCLUSIONS: Dosimetry
of all plans tested was robust to couch shifts up to +/-2 cm. In general, couch
shifts resulted in clinically insignificant dosimetric deviations. It is
conceivable that in certain cases with large systematic couch shifts and plans
that are particularly sensitive to shifts, dosimetric changes might rise to a
clinically significant level.
PMID- 27487869
TI - Use of radiochromic film as a high-spatial resolution dosimeter by Raman
spectroscopy.
AB - PURPOSE: Due to increasing demand for high-spatial resolution dosimetry,
radiochromic films have been investigated as potential candidates but are often
limited by the scanning system, e.g., flatbed optical scanner. In this study,
Raman spectroscopy in conjunction with a microscope was selected as an
alternative method for high-spatial resolution dosimetry of radiochromic film.
METHODS: Unlaminated GafchromicTM EBT3 films were irradiated with doses between 0
and 50 Gy using 6 MV x-rays of a clinical linear accelerator. Depth profiling
from the surface of unlaminated film was performed to acquire the maximum Raman
intensity peaks of C=C and C=C stretching bands of diacetylene polymer. The Raman
mapping technique for a region of interest (200 * 200, 30 * 30 MUm(2)) was
developed to reduce a large variation in a Raman spectrum produced with a
sampling resolution of a few MUm. The preprocessing of Raman spectra was carried
out to determine a dosimetric relationship with the amount of diacetylene
polymerization. RESULTS: Due to partial diacetylene polymerization upon
irradiation, two Raman peaks of C=C and C=C stretching bands were observed around
1447 and 2060 cm(-1), respectively. The maximum intensities of the two peaks were
obtained by positioning a focused laser spot on the surface of unlaminated film.
For the dose range of 0-50 Gy, the band heights of both C=C and C=C peaks
increase asymptotically with increasing doses and can be fit with an exponential
function of two components. The relative standard deviation in Raman mapping was
found to be less than +/-5%. By using this technique, dose uniformity was found
to be within +/-2%. CONCLUSIONS: The Raman intensity for C=C and C=C peaks
increases with an increase in the amount of diacetylene polymerization due to an
increase in dose. This study shows the potential of Raman spectroscopy as an
alternative for absolute dosimetry verifications with a high-spatial resolution
of a few MUm, but these findings need to be further validated for the purpose of
microdosimetry.
PMID- 27487870
TI - Library based x-ray scatter correction for dedicated cone beam breast CT.
AB - PURPOSE: The image quality of dedicated cone beam breast CT (CBBCT) is limited by
substantial scatter contamination, resulting in cupping artifacts and contrast
loss in reconstructed images. Such effects obscure the visibility of soft-tissue
lesions and calcifications, which hinders breast cancer detection and diagnosis.
In this work, we propose a library-based software approach to suppress scatter on
CBBCT images with high efficiency, accuracy, and reliability. METHODS: The
authors precompute a scatter library on simplified breast models with different
sizes using the geant4-based Monte Carlo (MC) toolkit. The breast is approximated
as a semiellipsoid with homogeneous glandular/adipose tissue mixture. For scatter
correction on real clinical data, the authors estimate the breast size from a
first-pass breast CT reconstruction and then select the corresponding scatter
distribution from the library. The selected scatter distribution from simplified
breast models is spatially translated to match the projection data from the
clinical scan and is subtracted from the measured projection for effective
scatter correction. The method performance was evaluated using 15 sets of patient
data, with a wide range of breast sizes representing about 95% of general
population. Spatial nonuniformity (SNU) and contrast to signal deviation ratio
(CDR) were used as metrics for evaluation. RESULTS: Since the time-consuming MC
simulation for library generation is precomputed, the authors' method efficiently
corrects for scatter with minimal processing time. Furthermore, the authors find
that a scatter library on a simple breast model with only one input parameter,
i.e., the breast diameter, sufficiently guarantees improvements in SNU and CDR.
For the 15 clinical datasets, the authors' method reduces the average SNU from
7.14% to 2.47% in coronal views and from 10.14% to 3.02% in sagittal views. On
average, the CDR is improved by a factor of 1.49 in coronal views and 2.12 in
sagittal views. CONCLUSIONS: The library-based scatter correction does not
require increase in radiation dose or hardware modifications, and it improves
over the existing methods on implementation simplicity and computational
efficiency. As demonstrated through patient studies, the authors' approach is
effective and stable, and is therefore clinically attractive for CBBCT imaging.
PMID- 27487871
TI - Robotic path-finding in inverse treatment planning for stereotactic radiosurgery
with continuous dose delivery.
AB - PURPOSE: Continuous dose delivery in radiation therapy treatments has been shown
to decrease total treatment time while improving the dose conformity and
distribution homogeneity over the conventional step-and-shoot approach. The
authors develop an inverse treatment planning method for Gamma Knife(r)
PerfexionTM that continuously delivers dose along a path in the target. METHODS:
The authors' method is comprised of two steps: find a path within the target,
then solve a mixed integer optimization model to find the optimal collimator
configurations and durations along the selected path. Robotic path-finding
techniques, specifically, simultaneous localization and mapping (SLAM) using an
extended Kalman filter, are used to obtain a path that travels sufficiently close
to selected isocentre locations. SLAM is novelly extended to explore a 3D,
discrete environment, which is the target discretized into voxels. Further novel
extensions are incorporated into the steering mechanism to account for target
geometry. RESULTS: The SLAM method was tested on seven clinical cases and
compared to clinical, Hamiltonian path continuous delivery, and inverse step-and
shoot treatment plans. The SLAM approach improved dose metrics compared to the
clinical plans and Hamiltonian path continuous delivery plans. Beam-on times
improved over clinical plans, and had mixed performance compared to Hamiltonian
path continuous plans. The SLAM method is also shown to be robust to path
selection inaccuracies, isocentre selection, and dose distribution. CONCLUSIONS:
The SLAM method for continuous delivery provides decreased total treatment time
and increased treatment quality compared to both clinical and inverse step-and
shoot plans, and outperforms existing path methods in treatment quality. It also
accounts for uncertainty in treatment planning by accommodating inaccuracies.
PMID- 27487872
TI - Interobserver variability in identification of breast tumors in MRI and its
implications for prognostic biomarkers and radiogenomics.
AB - PURPOSE: To assess the interobserver variability of readers when outlining breast
tumors in MRI, study the reasons behind the variability, and quantify the effect
of the variability on algorithmic imaging features extracted from breast MRI.
METHODS: Four readers annotated breast tumors from the MRI examinations of 50
patients from one institution using a bounding box to indicate a tumor. All of
the annotated tumors were biopsy proven cancers. The similarity of bounding boxes
was analyzed using Dice coefficients. An automatic tumor segmentation algorithm
was used to segment tumors from the readers' annotations. The segmented tumors
were then compared between readers using Dice coefficients as the similarity
metric. Cases showing high interobserver variability (average Dice coefficient
<0.8) after segmentation were analyzed by a panel of radiologists to identify the
reasons causing the low level of agreement. Furthermore, an imaging feature,
quantifying tumor and breast tissue enhancement dynamics, was extracted from each
segmented tumor for a patient. Pearson's correlation coefficients were computed
between the features for each pair of readers to assess the effect of the
annotation on the feature values. Finally, the authors quantified the extent of
variation in feature values caused by each of the individual reasons for low
agreement. RESULTS: The average agreement between readers in terms of the overlap
(Dice coefficient) of the bounding box was 0.60. Automatic segmentation of tumor
improved the average Dice coefficient for 92% of the cases to the average value
of 0.77. The mean agreement between readers expressed by the correlation
coefficient for the imaging feature was 0.96. CONCLUSIONS: There is a moderate
variability between readers when identifying the rectangular outline of breast
tumors on MRI. This variability is alleviated by the automatic segmentation of
the tumors. Furthermore, the moderate interobserver variability in terms of the
bounding box does not translate into a considerable variability in terms of
assessment of enhancement dynamics. The authors propose some additional ways to
further reduce the interobserver variability.
PMID- 27487873
TI - Validation of a pretreatment delivery quality assurance method for the CyberKnife
Synchrony system.
AB - PURPOSE: To evaluate the geometric and dosimetric accuracies of the CyberKnife
Synchrony respiratory tracking system (RTS) and to validate a method for
pretreatment patient-specific delivery quality assurance (DQA). METHODS: An
EasyCube phantom was mounted on the ExacTrac gating phantom, which can move along
the superior-inferior (SI) axis of a patient to simulate a moving target. The
authors compared dynamic and static measurements. For each case, a Gafchromic
EBT3 film was positioned between two slabs of the EasyCube, while a PinPoint
ionization chamber was placed in the appropriate space. There were three steps to
their evaluation: (1) the field size, the penumbra, and the symmetry of six
secondary collimators were measured along the two main orthogonal axes. Dynamic
measurements with deliberately simulated errors were also taken. (2) The
delivered dose distributions (from step 1) were compared with the planned ones,
using the gamma analysis method. The local gamma passing rates were evaluated
using three acceptance criteria: 3% local dose difference (LDD)/3 mm, 2%LDD/2 mm,
and 3%LDD/1 mm. (3) The DQA plans for six clinical patients were irradiated in
different dynamic conditions, to give a total of 19 cases. The measured and
planned dose distributions were evaluated with the same gamma-index criteria used
in step 2 and the measured chamber doses were compared with the planned mean
doses in the sensitive volume of the chamber. RESULTS: (1) A very slight
enlargement of the field size and of the penumbra was observed in the SI
direction (on average <1 mm), in line with the overall average CyberKnife system
error for tracking treatments. (2) Comparison between the planned and the
correctly delivered dose distributions confirmed the dosimetric accuracy of the
RTS for simple plans. The multicriteria gamma analysis was able to detect the
simulated errors, proving the robustness of their method of analysis. (3) All of
the DQA clinical plans passed the tests, both in static and dynamic conditions.
No statistically significant differences were found between static and dynamic
cases, confirming the high degree of accuracy of the Synchrony RTS. CONCLUSIONS:
The presented methods and measurements verified the mechanical and dosimetric
accuracy of the Synchrony RTS. Their method confirms the fact that the RTS, if
used properly, is able to treat a moving target with great precision. By
combining PinPoint ion chamber, EBT3 films, and gamma evaluation of dose
distributions, their DQA method robustly validated the effectiveness of
CyberKnife and Synchrony system.
PMID- 27487874
TI - An online replanning method using warm start optimization and aperture morphing
for flattening-filter-free beams.
AB - PURPOSE: In a situation where a couch shift for patient positioning is not
preferred or prohibited (e.g., MR-linac), segment aperture morphing (SAM) can
address target dislocation and deformation. For IMRT/VMAT with flattening-filter
free (FFF) beams, however, SAM method would lead to an adverse translational dose
effect due to the beam unflattening. Here the authors propose a new two-step
process to address both the translational effect of FFF beams and the target
deformation. METHODS: The replanning method consists of an offline and an online
step. The offline step is to create a series of preshifted-plans (PSPs) obtained
by a so-called "warm start" optimization (starting optimization from the original
plan, rather than from scratch) at a series of isocenter shifts. The PSPs all
have the same number of segments with very similar shapes, since the warm start
optimization only adjusts the MLC positions instead of regenerating them. In the
online step, a new plan is obtained by picking the closest PSP or linearly
interpolating the MLC positions and the monitor units of the closest PSPs for the
shift determined from the image of the day. This two-step process is completely
automated and almost instantaneous (no optimization or dose calculation needed).
The previously developed SAM algorithm is then applied for daily deformation. The
authors tested the method on sample prostate and pancreas cases. RESULTS: The two
step interpolation method can account for the adverse dose effects from FFF
beams, while SAM corrects for the target deformation. Plan interpolation method
is effective in diminishing the unflat beam effect and may allow reducing the
required number of PSPs. The whole process takes the same time as the previously
reported SAM process (5-10 min). CONCLUSIONS: The new two-step method plus SAM
can address both the translation effects of FFF beams and target deformation, and
can be executed in full automation except the delineation of target contour
required by the SAM process.
PMID- 27487875
TI - Optical CT imaging of solid radiochromic dosimeters in mismatched refractive
index solutions using a scanning laser and large area detector.
AB - PURPOSE: The practical use of the PRESAGE(r) solid plastic dosimeter is limited
by the inconvenience of immersing it in high-viscosity oils to achieve refractive
index matching for optical computed tomography (CT) scanning. The oils are slow
to mix and difficult to clean from surfaces, and the dosimeter rotation can
generate dynamic Schlieren inhomogeneity patterns in the reference liquid,
limiting the rotational and overall scan speed. Therefore, it would be beneficial
if lower-viscosity, water-based solutions with slightly unmatched refractive
index could be used instead. The purpose of this work is to demonstrate the
feasibility of allowing mismatched conditions when using a scanning laser system
with a large acceptance angle detector. A fiducial-based ray path measurement
technique is combined with an iterative CT reconstruction algorithm to
reconstruct images. METHODS: A water based surrounding liquid with a low
viscosity was selected for imaging PRESAGE(r) solid dosimeters. Liquid selection
was optimized to achieve as high a refractive index as possible while avoiding
rotation-induced Schlieren effects. This led to a refractive index mismatch of 6%
between liquid and dosimeters. Optical CT scans were performed with a fan-beam
scanning-laser optical CT system with a large area detector to capture most of
the refracted rays. A fiducial marker placed on the wall of a cylindrical sample
occludes a given light ray twice. With knowledge of the rotation angle and the
radius of the cylindrical object, the actual internal path of each ray through
the dosimeter can be calculated. Scans were performed with 1024 projections of
512 data samples each, and rays were rebinned to form 512 parallel-beam
projections. Reconstructions were performed on a 512 * 512 grid using 100
iterations of the SIRT iterative CT algorithm. Proof of concept was demonstrated
with a uniformly attenuating solution phantom. PRESAGE(r) dosimeters (11 cm
diameter) were irradiated with Cobalt-60 irradiator to achieve either a uniform
dose or a 2-level "step-dose" pattern. RESULTS: With 6% refractive index
mismatching, a circular field of view of 85% of the diameter of a cylindrical
sample can be reconstructed accurately. Reconstructed images of the test solution
phantom were uniform (within 3%) inside this radius. However, the dose responses
of the PRESAGE(r) samples were not spatially uniform, with variations of at least
5% in sensitivity. The variation appears as a "cupping" artifact with less
sensitivity in the middle than at the periphery of the PRESAGE(r) cylinder.
Polarization effects were also detected for these samples. CONCLUSIONS: The
fiducial-based ray path measurement scheme, coupled with an iterative
reconstruction algorithm, enabled optical CT scanning of PRESAGE(r) dosimeters
immersed in mismatched refractive index solutions. However, improvements to
PRESAGE(r) dose response uniformity are required.
PMID- 27487876
TI - Energy dependent response of plastic scintillation detectors to photon radiation
of low to medium energy.
AB - PURPOSE: Plastic scintillation detectors are promising candidates for the
dosimetry of low- to medium-energy photons but quantitative knowledge of their
energy response is a prerequisite for their correct use. The purpose of this
study was to characterize the energy dependent response of small scintillation
detectors (active volume <1 mm(3)) made from the commonly used plastic
scintillator BC400. METHODS: Different detectors made from BC400 were calibrated
at a number of radiation qualities ranging from 10 to 280 kV and at a (60)Co
beam. All calibrations were performed at the Physikalisch-Technische
Bundesanstalt, the National Metrology Institute of Germany. The energy response
in terms of air kerma, dose to water, and dose to the scintillator was
determined. Conversion factors from air kerma to dose to water and to dose to the
scintillator were derived from Monte Carlo simulations. In order to
quantitatively describe the energy dependence, a semiempirical model known as
unimolecular quenching or Birks' formula was fitted to the data and from this the
response to secondary electrons generated within the scintillator material BC400
was derived. RESULTS: The detector energy response in terms of air kerma differs
for different scintillator sizes and different detector casings. It is therefore
necessary to take attenuation within the scintillator and in the casing into
account when deriving the response in terms of dose to water from a calibration
in terms of air kerma. The measured energy response in terms of dose to water for
BC400 cannot be reproduced by the ratio of mean mass energy-absorption
coefficients for polyvinyl toluene to water but shows evidence of quenching. The
quenching parameter kB in Birks' formula was determined to be kB = (12.3 +/- 0.9)
mg MeV(-1) cm(-2). CONCLUSIONS: The energy response was quantified relative to
the response to (60)Co which is the common radiation quality for the calibration
of therapy dosemeters. The observed energy dependence could be well explained
with the assumption of ionization quenching as described by Birks' formula.
Plastic scintillation detectors should be calibrated at the same radiation
quality that they will be used at and changes of the spectrum within the
application need to be considered. The authors results can be used to evaluate
the range of validity of a given calibration.
PMID- 27487877
TI - Multisource inverse-geometry CT. Part I. System concept and development.
AB - PURPOSE: This paper presents an overview of multisource inverse-geometry computed
tomography (IGCT) as well as the development of a gantry-based research prototype
system. The development of the distributed x-ray source is covered in a companion
paper [V. B. Neculaes et al., "Multisource inverse-geometry CT. Part II. X-ray
source design and prototype," Med. Phys. 43, 4617-4627 (2016)]. While progress
updates of this development have been presented at conferences and in journal
papers, this paper is the first comprehensive overview of the multisource inverse
geometry CT concept and prototype. The authors also provide a review of all
previous IGCT related publications. METHODS: The authors designed and implemented
a gantry-based 32-source IGCT scanner with 22 cm field-of-view, 16 cm z-coverage,
1 s rotation time, 1.09 * 1.024 mm detector cell size, as low as 0.4 * 0.8 mm
focal spot size and 80-140 kVp x-ray source voltage. The system is built using
commercially available CT components and a custom made distributed x-ray source.
The authors developed dedicated controls, calibrations, and reconstruction
algorithms and evaluated the system performance using phantoms and small animals.
RESULTS: The authors performed IGCT system experiments and demonstrated tube
current up to 125 mA with up to 32 focal spots. The authors measured a spatial
resolution of 13 lp/cm at 5% cutoff. The scatter-to-primary ratio is estimated
62% for a 32 cm water phantom at 140 kVp. The authors scanned several phantoms
and small animals. The initial images have relatively high noise due to the low x
ray flux levels but minimal artifacts. CONCLUSIONS: IGCT has unique benefits in
terms of dose-efficiency and cone-beam artifacts, but comes with challenges in
terms of scattered radiation and x-ray flux limits. To the authors' knowledge,
their prototype is the first gantry-based IGCT scanner. The authors summarized
the design and implementation of the scanner and the authors presented results
with phantoms and small animals.
PMID- 27487878
TI - Multisource inverse-geometry CT. Part II. X-ray source design and prototype.
AB - PURPOSE: This paper summarizes the development of a high-power distributed x-ray
source, or "multisource," designed for inverse-geometry computed tomography (CT)
applications [see B. De Man et al., "Multisource inverse-geometry CT. Part I.
System concept and development," Med. Phys. 43, 4607-4616 (2016)]. The paper
presents the evolution of the source architecture, component design (anode,
emitter, beam optics, control electronics, high voltage insulator), and
experimental validation. METHODS: Dispenser cathode emitters were chosen as
electron sources. A modular design was adopted, with eight electron emitters (two
rows of four emitters) per module, wherein tungsten targets were brazed onto
copper anode blocks-one anode block per module. A specialized ceramic connector
provided high voltage standoff capability and cooling oil flow to the anode. A
matrix topology and low-noise electronic controls provided switching of the
emitters. RESULTS: Four modules (32 x-ray sources in two rows of 16) have been
successfully integrated into a single vacuum vessel and operated on an inverse
geometry computed tomography system. Dispenser cathodes provided high beam
current (>1000 mA) in pulse mode, and the electrostatic lenses focused the
current beam to a small optical focal spot size (0.5 * 1.4 mm). Controlled
emitter grid voltage allowed the beam current to be varied for each source,
providing the ability to modulate beam current across the fan of the x-ray beam,
denoted as a virtual bowtie filter. The custom designed controls achieved x-ray
source switching in <1 MUs. The cathode-grounded source was operated successfully
up to 120 kV. CONCLUSIONS: A high-power, distributed x-ray source for inverse
geometry CT applications was successfully designed, fabricated, and operated.
Future embodiments may increase the number of spots and utilize fast read out
detectors to increase the x-ray flux magnitude further, while still staying
within the stationary target inherent thermal limitations.
PMID- 27487879
TI - First evaluation of the feasibility of MLC tracking using ultrasound motion
estimation.
AB - PURPOSE: To quantify the performance of the Clarity ultrasound (US) imaging
system (Elekta AB, Stockholm, Sweden) for real-time dynamic multileaf collimator
(MLC) tracking. METHODS: The Clarity calibration and quality assurance phantom
was mounted on a motion platform moving with a periodic sine wave trajectory. The
detected position of a 30 mm hypoechogenic sphere within the phantom was
continuously reported via Clarity's real-time streaming interface to an in-house
tracking and delivery software and subsequently used to adapt the MLC aperture. A
portal imager measured MV treatment field/MLC apertures and motion platform
positions throughout each experiment to independently quantify system latency and
geometric error. Based on the measured range of latency values, a prostate
stereotactic body radiation therapy (SBRT) delivery was performed with three
realistic motion trajectories. The dosimetric impact of system latency on MLC
tracking was directly measured using a 3D dosimeter mounted on the motion
platform. RESULTS: For 2D US imaging, the overall system latency, including all
delay times from the imaging and delivery chain, ranged from 392 to 424 ms
depending on the lateral sector size. For 3D US imaging, the latency ranged from
566 to 1031 ms depending on the elevational sweep. The latency-corrected
geometric root-mean squared error was below 0.75 mm (2D US) and below 1.75 mm (3D
US). For the prostate SBRT delivery, the impact of a range of system latencies
(400-1000 ms) on the MLC tracking performance was minimal in terms of gamma
failure rate. CONCLUSIONS: Real-time MLC tracking based on a noninvasive US input
is technologically feasible. Current system latencies are higher than those for x
ray imaging systems, but US can provide full volumetric image data and the impact
of system latency was measured to be small for a prostate SBRT case when using a
US-like motion input.
PMID- 27487880
TI - Feasibility of MRI-only treatment planning for proton therapy in brain and
prostate cancers: Dose calculation accuracy in substitute CT images.
AB - PURPOSE: Magnetic resonance imaging (MRI) is increasingly used for radiotherapy
target delineation, image guidance, and treatment response monitoring. Recent
studies have shown that an entire external x-ray radiotherapy treatment planning
(RTP) workflow for brain tumor or prostate cancer patients based only on MRI
reference images is feasible. This study aims to show that a MRI-only based RTP
workflow is also feasible for proton beam therapy plans generated in MRI-based
substitute computed tomography (sCT) images of the head and the pelvis. METHODS:
The sCTs were constructed for ten prostate cancer and ten brain tumor patients
primarily by transforming the intensity values of in-phase MR images to
Hounsfield units (HUs) with a dual model HU conversion technique to enable
heterogeneous tissue representation. HU conversion models for the pelvis were
adopted from previous studies, further extended in this study also for head MRI
by generating anatomical site-specific conversion models (a new training data set
of ten other brain patients). This study also evaluated two other types of
simplified sCT: dual bulk density (for bone and water) and homogeneous (water
only). For every clinical case, intensity modulated proton therapy (IMPT) plans
robustly optimized in standard planning CTs were calculated in sCT for
evaluation, and vice versa. Overall dose agreement was evaluated using dose
volume histogram parameters and 3D gamma criteria. RESULTS: In heterogeneous
sCTs, the mean absolute errors in HUs were 34 (soft tissues: 13, bones: 92) and
42 (soft tissues: 9, bones: 97) in the head and in the pelvis, respectively. The
maximum absolute dose differences relative to CT in the brain tumor clinical
target volume (CTV) were 1.4% for heterogeneous sCT, 1.8% for dual bulk sCT, and
8.9% for homogenous sCT. The corresponding maximum differences in the prostate
CTV were 0.6%, 1.2%, and 3.6%, respectively. The percentages of dose points in
the head and pelvis passing 1% and 1 mm gamma index criteria were over 91%, 85%,
and 38% with heterogeneous, dual bulk, and homogeneous sCTs, respectively. There
were no significant changes to gamma index pass rates for IMPT plans first
optimized in CT and then calculated in heterogeneous sCT versus IMPT plans first
optimized in heterogeneous sCT and then calculated on standard CT. CONCLUSIONS:
This study demonstrates that proton therapy dose calculations on heterogeneous
sCTs are in good agreement with plans generated with standard planning CT. An MRI
only based RTP workflow is feasible in IMPT for brain tumors and prostate
cancers.
PMID- 27487881
TI - Reconstruction of implanted marker trajectories from cone-beam CT projection
images using interdimensional correlation modeling.
AB - PURPOSE: Cone-beam CT (CBCT) is a widely used imaging modality for image-guided
radiotherapy. Most vendors provide CBCT systems that are mounted on a linac
gantry. Thus, CBCT can be used to estimate the actual 3-dimensional (3D) position
of moving respiratory targets in the thoracic/abdominal region using 2D
projection images. The authors have developed a method for estimating the 3D
trajectory of respiratory-induced target motion from CBCT projection images using
interdimensional correlation modeling. METHODS: Because the superior-inferior
(SI) motion of a target can be easily analyzed on projection images of a gantry
mounted CBCT system, the authors investigated the interdimensional correlation of
the SI motion with left-right and anterior-posterior (AP) movements while the
gantry is rotating. A simple linear model and a state-augmented model were
implemented and applied to the interdimensional correlation analysis, and their
performance was compared. The parameters of the interdimensional correlation
models were determined by least-square estimation of the 2D error between the
actual and estimated projected target position. The method was validated using
160 3D tumor trajectories from 46 thoracic/abdominal cancer patients obtained
during CyberKnife treatment. The authors' simulations assumed two application
scenarios: (1) retrospective estimation for the purpose of moving tumor setup
used just after volumetric matching with CBCT; and (2) on-the-fly estimation for
the purpose of real-time target position estimation during gating or tracking
delivery, either for full-rotation volumetric-modulated arc therapy (VMAT) in 60
s or a stationary six-field intensity-modulated radiation therapy (IMRT) with a
beam delivery time of 20 s. RESULTS: For the retrospective CBCT simulations, the
mean 3D root-mean-square error (RMSE) for all 4893 trajectory segments was 0.41
mm (simple linear model) and 0.35 mm (state-augmented model). In the on-the-fly
simulations, prior projections over more than 60 degrees appear to be necessary
for reliable estimations. The mean 3D RMSE during beam delivery after the simple
linear model had established with a prior 90 degrees projection data was 0.42 mm
for VMAT and 0.45 mm for IMRT. CONCLUSIONS: The proposed method does not require
any internal/external correlation or statistical modeling to estimate the target
trajectory and can be used for both retrospective image-guided radiotherapy with
CBCT projection images and real-time target position monitoring for respiratory
gating or tracking.
PMID- 27487882
TI - A model of tungsten anode x-ray spectra.
AB - PURPOSE: A semiempirical model for x-ray production in tungsten thick-targets was
evaluated using a new characterization of electron fluence. METHODS: Electron
fluence is modeled taking into account both the energy and angular distributions,
each of them adjusted to Monte Carlo simulated data. Distances were scaled by the
CSDA range to reduce the energy dependence. Bremsstrahlung production was found
by integrating the cross section with the fluence in a 1D penetration model.
Characteristic radiation was added using a semiempirical law whose validity was
checked. The results were compared the experimental results of Bhat et al., with
the SpekCalc numerical tool, and with mcnpx simulation results from the work of
Hernandez and Boone. RESULTS: The model described shows better agreement with the
experimental results than the SpekCalc predictions in the sense of area between
the spectra. A general improvement of the predictions of half-value layers is
also found. The results are also in good agreement with the simulation results in
the 50-640 keV energy range. CONCLUSIONS: A complete model for x-ray production
in thick bremsstrahlung targets has been developed, improving the results of
previous works and extending the energy range covered to the 50-640 keV interval.
PMID- 27487883
TI - Backscatter dose effects for high atomic number materials being irradiated in the
presence of a magnetic field: A Monte Carlo study for the MRI linac.
AB - PURPOSE: To quantify and explain the backscatter dose effects for clinically
relevant high atomic number materials being irradiated in the presence of a 1.5 T
transverse magnetic field. METHODS: Interface effects were investigated using
Monte Carlo simulation techniques. We used gpumcd (v5.1) and geant4 (v10.1) for
this purpose. gpumcd is a commercial software written for the Elekta AB, MRI
linac. Dose was scored using gpumcd in cubic voxels of side 1 and 0.5 mm, in two
different virtual phantoms of dimensions 20 * 20 * 20 cm and 5 * 5 * 13.3 cm,
respectively. A photon beam was generated from a point 143.5 cm away from the
isocenter with energy distribution sampled from a histogram representing the true
Elekta, MRI linac photon spectrum. A slab of variable thickness and position
containing either bone, aluminum, titanium, stainless steel, or one of the two
different dental filling materials was inserted as an inhomogeneity in the 20 *
20 * 20 cm phantom. The 5 * 5 * 13.3 cm phantom was used as a clinical test case
in order to explain the dose perturbation effects for a head and neck cancer
patient. The back scatter dose factor (BSDF) was defined as the ratio of the
doses at a given depth with and without the presence of the inhomogeneity.
Backscattered electron fluence was calculated at the inhomogeneity interface
using geant4. A 1.5 T magnetic field was applied perpendicular to the direction
of the beam in both phantoms, identical to the geometry in the Elekta MRI linac.
RESULTS: With the application of a 1.5 T magnetic field, all the BSDF's were
reduced by 12%-47%, compared to the no magnetic field case. The corresponding
backscattered electron fluence at the interface was also reduced by 45%-64%. The
reduction in the BSDF at the interface, due to the application of the magnetic
field, is manifested in a different manner for each material. In the case of
bone, the dose drops at the interface contrary to the expected increase when no
magnetic field is applied. In the case of aluminum, the dose at the interface is
the same with and without the presence of the aluminum. For all of the other
materials the dose increases at the interface. CONCLUSIONS: The reduction in dose
at the interface, in the presence of the magnetic field, is directly related to
the reduction in backscattered electron fluence. This reduction occurs due to two
different reasons. First, the electron spectrum hitting the interface is changed
when the magnetic field is turned on, which results in changes in the electron
scattering probability. Second, some electrons that have curved trajectories due
to the presence of the magnetic field are absorbed by the higher density side of
the interface and no longer contribute to the backscattered electron fluence.
PMID- 27487884
TI - Experimental feasibility of multistatic holography for breast microwave radar
image reconstruction.
AB - PURPOSE: The goal of this study was to assess the experimental feasibility of
circular multistatic holography, a novel breast microwave radar reconstruction
approach, using experimental datasets recorded using a preclinical experimental
setup. The performance of this approach was quantitatively evaluated by
calculating the signal to clutter ratio (SCR), contrast to clutter ratio (CCR),
tumor to fibroglandular response ratio (TFRR), spatial accuracy, and
reconstruction time. METHODS: Five datasets were recorded using synthetic
phantoms with the dielectric properties of breast tissue in the 1-6 GHz range
using a custom radar system developed by the authors. The datasets contained
synthetic structures that mimic the dielectric properties of fibroglandular
breast tissues. Four of these datasets the authors covered an 8 mm inclusion that
emulated a tumor. A custom microwave radar system developed at the University of
Manitoba was used to record the radar responses from the phantoms. The datasets
were reconstructed using the proposed multistatic approach as well as with a
monostatic holography approach that has been previously shown to yield the images
with the highest contrast and focal quality. RESULTS: For all reconstructions,
the location of the synthetic tumors in the experimental setup was consistent
with the position in the both the monostatic and multistatic reconstructed
images. The average spatial error was less than 4 mm, which is half the spatial
resolution of the data acquisition system. The average SCR, CCR, and TFRR of the
images reconstructed with the multistatic approach were 15.0, 9.4, and 10.0 dB,
respectively. In comparison, monostatic images obtained using the datasets from
the same experimental setups yielded average SCR, CCR, and TFRR values of 12.8,
4.9, and 5.9 dB. No artifacts, defined as responses generated by the
reconstruction method of at least half the energy of the tumor signatures, were
noted in the multistatic reconstructions. The average execution time of the
images formed using the proposed approach was 4 s, which is one order of
magnitude faster than the current state-of-the-art time-domain multistatic breast
microwave radar reconstruction algorithms. CONCLUSIONS: The images generated by
the proposed method show that multistatic holography is capable of forming
spatially accurate images in real-time with signal to clutter levels and contrast
values higher than other published monostatic and multistatic cylindrical radar
reconstruction approaches. In comparison to the monostatic holographic approach,
the images generated by the proposed multistatic approach had SCR values that
were at least 50% higher. The multistatic images had CCR and TFRR values at least
200% greater than those formed using a monostatic approach.
PMID- 27487885
TI - An experimental extrapolation technique using the Gafchromic EBT3 film for
relative output factor measurements in small x-ray fields.
AB - PURPOSE: An experimental extrapolation technique is presented, which can be used
to determine the relative output factors for very small x-ray fields using the
Gafchromic EBT3 film. METHODS: Relative output factors were measured for the
Brainlab SRS cones ranging in diameters from 4 to 30 mm(2) on a Novalis Trilogy
linear accelerator with 6 MV SRS x-rays. The relative output factor was
determined from an experimental reducing circular region of interest (ROI)
extrapolation technique developed to remove the effects of volume averaging. This
was achieved by scanning the EBT3 film measurements with a high scanning
resolution of 1200 dpi. From the high resolution scans, the size of the circular
regions of interest was varied to produce a plot of relative output factors
versus area of analysis. The plot was then extrapolated to zero to determine the
relative output factor corresponding to zero volume. RESULTS: Results have shown
that for a 4 mm field size, the extrapolated relative output factor was measured
as a value of 0.651 +/- 0.018 as compared to 0.639 +/- 0.019 and 0.633 +/- 0.021
for 0.5 and 1.0 mm diameter of analysis values, respectively. This showed a
change in the relative output factors of 1.8% and 2.8% at these comparative
regions of interest sizes. In comparison, the 25 mm cone had negligible
differences in the measured output factor between zero extrapolation, 0.5 and 1.0
mm diameter ROIs, respectively. CONCLUSIONS: This work shows that for very small
fields such as 4.0 mm cone sizes, a measureable difference can be seen in the
relative output factor based on the circular ROI and the size of the area of
analysis using radiochromic film dosimetry. The authors recommend to scan the
Gafchromic EBT3 film at a resolution of 1200 dpi for cone sizes less than 7.5 mm
and to utilize an extrapolation technique for the output factor measurements of
very small field dosimetry.
PMID- 27487886
TI - Technical Note: A treatment plan comparison between dynamic collimation and a
fixed aperture during spot scanning proton therapy for brain treatment.
AB - PURPOSE: To quantitatively assess the advantages of energy-layer specific dynamic
collimation system (DCS) versus a per-field fixed aperture for spot scanning
proton therapy (SSPT). METHODS: Five brain cancer patients previously planned and
treated with SSPT were replanned using an in-house treatment planning system
capable of modeling collimated and uncollimated proton beamlets. The uncollimated
plans, which served as a baseline for comparison, reproduced the target coverage
and organ-at-risk sparing of the clinically delivered plans. The collimator
opening for the fixed aperture-based plans was determined from the combined cross
sections of the target in the beam's eye view over all energy layers which
included an additional margin equivalent to the maximum beamlet displacement for
the respective energy of that energy layer. The DCS-based plans were created by
selecting appropriate collimator positions for each row of beam spots during a
Raster-style scanning pattern which were optimized to maximize the dose
contributions to the target and limited the dose delivered to adjacent normal
tissue. RESULTS: The reduction of mean dose to normal tissue adjacent to the
target, as defined by a 10 mm ring surrounding the target, averaged 13.65%
(range: 11.8%-16.9%) and 5.18% (2.9%-7.1%) for the DCS and fixed aperture plans,
respectively. The conformity index, as defined by the ratio of the volume of the
50% isodose line to the target volume, yielded an average improvement of 21.35%
(19.4%-22.6%) and 8.38% (4.7%-12.0%) for the DCS and fixed aperture plans,
respectively. CONCLUSIONS: The ability of the DCS to provide collimation to each
energy layer yielded better conformity in comparison to fixed aperture plans.
PMID- 27487887
TI - An integrated model-driven method for in-treatment upper airway motion tracking
using cine MRI in head and neck radiation therapy.
AB - PURPOSE: For the first time, MRI-guided radiation therapy systems can acquire
cine images to dynamically monitor in-treatment internal organ motion. However,
the complex head and neck (H&N) structures and low-contrast/resolution of on
board cine MRI images make automatic motion tracking a very challenging task. In
this study, the authors proposed an integrated model-driven method to
automatically track the in-treatment motion of the H&N upper airway, a complex
and highly deformable region wherein internal motion often occurs in an either
voluntary or involuntary manner, from cine MRI images for the analysis of H&N
motion patterns. METHODS: Considering the complex H&N structures and ensuring
automatic and robust upper airway motion tracking, the authors firstly built a
set of linked statistical shapes (including face, face-jaw, and face-jaw-palate)
using principal component analysis from clinically approved contours delineated
on a set of training data. The linked statistical shapes integrate explicit
landmarks and implicit shape representation. Then, a hierarchical model-fitting
algorithm was developed to align the linked shapes on the first image frame of a
to-be-tracked cine sequence and to localize the upper airway region. Finally, a
multifeature level set contour propagation scheme was performed to identify the
upper airway shape change, frame-by-frame, on the entire image sequence. The
multifeature fitting energy, including the information of intensity variations,
edge saliency, curve geometry, and temporal shape continuity, was minimized to
capture the details of moving airway boundaries. Sagittal cine MR image sequences
acquired from three H&N cancer patients were utilized to demonstrate the
performance of the proposed motion tracking method. RESULTS: The tracking
accuracy was validated by comparing the results to the average of two manual
delineations in 50 randomly selected cine image frames from each patient. The
resulting average dice similarity coefficient (93.28% +/- 1.46%) and margin
error (0.49 +/- 0.12 mm) showed good agreement between the automatic and manual
results. The comparison with three other deformable model-based segmentation
methods illustrated the superior shape tracking performance of the proposed
method. Large interpatient variations of swallowing frequency, swallowing
duration, and upper airway cross-sectional area were observed from the testing
cine image sequences. CONCLUSIONS: The proposed motion tracking method can
provide accurate upper airway motion tracking results, and enable automatic and
quantitative identification and analysis of in-treatment H&N upper airway motion.
By integrating explicit and implicit linked-shape representations within a
hierarchical model-fitting process, the proposed tracking method can process
complex H&N structures and low-contrast/resolution cine MRI images. Future
research will focus on the improvement of method reliability, patient motion
pattern analysis for providing more information on patient-specific prediction of
structure displacements, and motion effects on dosimetry for better H&N motion
management in radiation therapy.
PMID- 27487888
TI - Technical Note: spektr 3.0-A computational tool for x-ray spectrum modeling and
analysis.
AB - PURPOSE: A computational toolkit (spektr 3.0) has been developed to calculate x
ray spectra based on the tungsten anode spectral model using interpolating cubic
splines (TASMICS) algorithm, updating previous work based on the tungsten anode
spectral model using interpolating polynomials (TASMIP) spectral model. The
toolkit includes a matlab (The Mathworks, Natick, MA) function library and
improved user interface (UI) along with an optimization algorithm to match
calculated beam quality with measurements. METHODS: The spektr code generates x
ray spectra (photons/mm(2)/mAs at 100 cm from the source) using TASMICS as
default (with TASMIP as an option) in 1 keV energy bins over beam energies 20-150
kV, extensible to 640 kV using the TASMICS spectra. An optimization tool was
implemented to compute the added filtration (Al and W) that provides a best match
between calculated and measured x-ray tube output (mGy/mAs or mR/mAs) for
individual x-ray tubes that may differ from that assumed in TASMICS or TASMIP and
to account for factors such as anode angle. RESULTS: The median percent
difference in photon counts for a TASMICS and TASMIP spectrum was 4.15% for tube
potentials in the range 30-140 kV with the largest percentage difference arising
in the low and high energy bins due to measurement errors in the empirically
based TASMIP model and inaccurate polynomial fitting. The optimization tool
reported a close agreement between measured and calculated spectra with a Pearson
coefficient of 0.98. CONCLUSIONS: The computational toolkit, spektr, has been
updated to version 3.0, validated against measurements and existing models, and
made available as open source code. Video tutorials for the spektr function
library, UI, and optimization tool are available.
PMID- 27487889
TI - Texture analyses of quantitative susceptibility maps to differentiate Alzheimer's
disease from cognitive normal and mild cognitive impairment.
AB - PURPOSE: Although a number of studies have focused on finding anatomical regions
in which iron concentrations are high, no study has been conducted to examine the
overall variations in susceptibility maps of Alzheimer's disease (AD). The
objective of this study, therefore, was to differentiate AD from cognitive normal
(CN) and mild cognitive impairment (MCI) using a texture analysis of quantitative
susceptibility maps (QSMs). METHODS: The study was approved by the local
institutional review board, and informed consent was obtained from all subjects.
In each participant group-CN, MCI, and AD-18 elderly subjects were enrolled. A
fully first-order flow-compensated 3D gradient-echo sequence was run to obtain
axial magnitudes and phase images and to produce QSM data. Sagittal structural 3D
T1-weighted (3DT1W) images were also obtained with the magnetization-prepared
rapid acquisition of gradient-echo sequence to obtain brain tissue images. The
first- and second-order texture parameters of the QSMs and 3DT1W images were
obtained to evaluate group differences using a one-way analysis of covariance.
RESULTS: For the first-order QSM analysis, mean, standard deviation, and
covariance of signal intensity separated the subject groups (F = 5.191, p =
0.009). For the second-order analysis, angular second moment, contrast, and
correlation separated the subject groups (F = 6.896, p = 0.002). Finally, a
receiver operating characteristic curve analysis differentiated MCI from CN in
white matter on the QSMs (z = 3.092, p = 0.0020). CONCLUSIONS: This was the first
study to evaluate the textures of QSM in AD, which overcame the limitations of
voxel-based analyses. The QSM texture analysis successfully distinguished both AD
and MCI from CN and outperformed the voxel-based analysis using 3DT1-weighed
images in separating MCI from CN. The first-order textures were more efficient in
differentiating MCI from CN than did the second-order.
PMID- 27487890
TI - Technical Note: Correction for intra-chamber dose gradients in reference
dosimetry of flattening-filter-free MV photon beams.
AB - PURPOSE: To estimate and correct for the volume averaging effect which results
from the intra-chamber dose gradients when a Farmer ionization chamber (IC) is
used for reference dosimetry in flattening-filter-free (FFF) MV photon beams.
METHODS: An intra-chamber dose gradients correction factor (kicdg) to the charge
reading of a Farmer IC is estimated by comparison to a small volume IC (~0.1
cm(3)), in the FFF beams of a TrueBeamTM (Varian, Inc.) linear accelerators. An
independent estimate of the correction for the volume averaging effect (pvol) is
deduced using the ratio of the active length (L) of the Farmer IC to the integral
of a high-resolution FFF radial dose profile over this same length. RESULTS: Mean
(sd) values for kicdg equal to 1.0025 (0.0025) for 6 MV-FFF, and equal to 1.0057
(0.0025) for 10 MV-FFF, were estimated based on four dosimetry sessions,
performed in a time interval of six months. Similarly, pvol (Farmer) equal to
1.0030 (0.0003) for 6 MV-FFF, and equal to 1.0063 (0.0005) for 10 MV-FFF, were
computed. CONCLUSIONS: The systematic bias which results from intra-chamber dose
gradients when a Farmer IC is used for reference dosimetry in FFF MV photon beams
is estimated to be -0.6% for 10 MV-FFF, and -0.3% for 6 MV-FFF, based on the
obtained values of the factor kicdg. This bias can be corrected, within 0.1%, by
the simple measure of pvol at the beginning of the dosimetry session.
PMID- 27487891
TI - Introduction of a novel ultrahigh sensitivity collimator for brain SPECT imaging.
AB - PURPOSE: Noise levels of brain SPECT images are highest in central regions, due
to preferential attenuation of photons emitted from deep structures. To address
this problem, the authors have designed a novel collimator for brain SPECT
imaging that yields greatly increased sensitivity near the center of the brain
without loss of resolution. This hybrid collimator consisted of ultrashort cone
beam holes in the central regions and slant-holes in the periphery (USCB). We
evaluated this collimator for quantitative brain imaging tasks. METHODS: Owing to
the uniqueness of the USCB collimation, the hole pattern required substantial
variations in collimator parameters. To utilize the lead-casting technique, the
authors designed two supporting plates to position about 37 000 hexagonal,
slightly tapered pins. The holes in the supporting plates were modeled to yield
the desired focal length, hole length, and septal thickness. To determine the
properties of the manufactured collimator and to compute the system matrix, the
authors prepared an array of point sources that covered the entire detector area.
Each point source contained 32 MUCi of Tc-99m at the first scan time. The array
was imaged for 5 min at each of the 64 shifted locations to yield a 2-mm sampling
distance, and hole parameters were calculated. The sensitivity was also measured
using a point source placed along the central ray at several distances from the
collimator face. High-count projection data from a five-compartment brain phantom
were acquired with the three collimators on a dual-head SPECT/CT system. The
authors calculated Cramer-Rao bounds on the precision of estimates of striatal
and background activity concentration. In order to assess the new collimation
system to detect changes in striatal activity, the authors evaluated the
precision of measuring a 5% decrease in right putamen activity. The authors also
reconstructed images of projection data obtained by summing data from the
individual phantom compartments. RESULTS: The sensitivity of the novel cone-beam
collimator varied with distance from the detector face; it was higher than that
of the fan-beam collimator by factors ranging from 2.7 to 162. Examination of the
projections of the point sources revealed that only a few holes were distorted or
partially blocked, indicating that the intensive manual fabrication process was
very successful. Better reconstructed phantom images were obtained from the
USCB+FAN collimator pair than from either LEHR or FAN collimation. For the left
caudate, located near the center of the brain, the detected counts were 9.8 (8.3)
times higher for UCSB compared with LEHR (FAN), averaged over 60 views. The task
specific SNR for detecting a 5% decrease in putamen uptake was 7.4 for USCB and
3.2 for LEHR. CONCLUSIONS: The authors have designed and manufactured a novel
collimator for brain SPECT imaging. The sensitivity is much higher than that of a
fan-beam collimator. Because of differences between the manufactured collimator
and its design, reconstruction of the data requires a measured system matrix. The
authors have demonstrated the potential of USCB collimation for improved
precision in estimating striatal uptake. The novel collimator may be useful for
early detection of Parkinson's disease, and for monitoring therapy response and
disease progression.
PMID- 27487892
TI - A patch-based pseudo-CT approach for MRI-only radiotherapy in the pelvis.
AB - PURPOSE: In radiotherapy based only on magnetic resonance imaging (MRI),
knowledge about tissue electron densities must be derived from the MRI. This can
be achieved by converting the MRI scan to the so-called pseudo-computed
tomography (pCT). An obstacle is that the voxel intensities in conventional MRI
scans are not uniquely related to electron density. The authors previously
demonstrated that a patch-based method could produce accurate pCTs of the brain
using conventional T1-weighted MRI scans. The method was driven mainly by local
patch similarities and relied on simple affine registrations between an atlas
database of the co-registered MRI/CT scan pairs and the MRI scan to be converted.
In this study, the authors investigate the applicability of the patch-based
approach in the pelvis. This region is challenging for a method based on local
similarities due to the greater inter-patient variation. The authors benchmark
the method against a baseline pCT strategy where all voxels inside the body
contour are assigned a water-equivalent bulk density. Furthermore, the authors
implement a parallelized approximate patch search strategy to speed up the pCT
generation time to a more clinically relevant level. METHODS: The data consisted
of CT and T1-weighted MRI scans of 10 prostate patients. pCTs were generated
using an approximate patch search algorithm in a leave-one-out fashion and
compared with the CT using frequently described metrics such as the voxel-wise
mean absolute error (MAEvox) and the deviation in water-equivalent path lengths.
Furthermore, the dosimetric accuracy was tested for a volumetric modulated arc
therapy plan using dose-volume histogram (DVH) point deviations and gamma-index
analysis. RESULTS: The patch-based approach had an average MAEvox of 54 HU;
median deviations of less than 0.4% in relevant DVH points and a gamma-index pass
rate of 0.97 using a 1%/1 mm criterion. The patch-based approach showed a
significantly better performance than the baseline water pCT in almost all
metrics. The approximate patch search strategy was 70x faster than a brute-force
search, with an average prediction time of 20.8 min. CONCLUSIONS: The authors
showed that a patch-based method based on affine registrations and T1-weighted
MRI could generate accurate pCTs of the pelvis. The main source of differences
between pCT and CT was positional changes of air pockets and body outline.
PMID- 27487893
TI - Optimization-based scatter estimation using primary modulation for computed
tomography.
AB - PURPOSE: Scatter reduces the image quality in computed tomography (CT), but
scatter correction remains a challenge. A previously proposed primary modulation
method simultaneously obtains the primary and scatter in a single scan. However,
separating the scatter and primary in primary modulation is challenging because
it is an underdetermined problem. In this study, an optimization-based scatter
estimation (OSE) algorithm is proposed to estimate and correct scatter. METHODS:
In the concept of primary modulation, the primary is modulated, but the scatter
remains smooth by inserting a modulator between the x-ray source and the object.
In the proposed algorithm, an objective function is designed for separating the
scatter and primary. Prior knowledge is incorporated in the optimization-based
framework to improve the accuracy of the estimation: (1) the primary is always
positive; (2) the primary is locally smooth and the scatter is smooth; (3) the
location of penumbra can be determined; and (4) the scatter-contaminated data
provide knowledge about which part is smooth. RESULTS: The simulation study shows
that the edge-preserving weighting in OSE improves the estimation accuracy near
the object boundary. Simulation study also demonstrates that OSE outperforms the
two existing primary modulation algorithms for most regions of interest in terms
of the CT number accuracy and noise. The proposed method was tested on a clinical
cone beam CT, demonstrating that OSE corrects the scatter even when the modulator
is not accurately registered. CONCLUSIONS: The proposed OSE algorithm improves
the robustness and accuracy in scatter estimation and correction. This method is
promising for scatter correction of various kinds of x-ray imaging modalities,
such as x-ray radiography, cone beam CT, and the fourth-generation CT.
PMID- 27487894
TI - Optimization of yttrium-90 PET for simultaneous PET/MR imaging: A phantom study.
AB - PURPOSE: Positron emission tomography (PET) imaging of yttrium-90 in the liver
post radioembolization has been shown useful for personalized dosimetry
calculations and evaluation of extrahepatic deposition. The purpose of this study
was to quantify the benefits of several MR-based data correction approaches
offered by using a combined PET/MR system to improve Y-90 PET imaging. In
particular, the feasibility of motion and partial volume corrections were
investigated in a controlled phantom study. METHODS: The ACR phantom was filled
with an initial concentration of 8 GBq of Y-90 solution resulting in a contrast
of 10:1 between the hot cylinders and the background. Y-90 PET motion correction
through motion estimates from MR navigators was evaluated by using a custom-built
motion stage that simulated realistic amplitudes of respiration-induced liver
motion. Finally, the feasibility of an MR-based partial volume correction method
was evaluated using a wavelet decomposition approach. RESULTS: Motion resulted in
a large (~40%) loss of contrast recovery for the 8 mm cylinder in the phantom,
but was corrected for after MR-based motion correction was applied. Partial
volume correction improved contrast recovery by 13% for the 8 mm cylinder.
CONCLUSIONS: MR-based data correction improves Y-90 PET imaging on simultaneous
PET/MR systems. Assessment of these methods must be studied further in the
clinical setting.
PMID- 27487895
TI - Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable
radiosensitizers.
AB - PURPOSE: Gold nanoparticles (GNPs) are being investigated actively for various
applications in cancer diagnosis and therapy. As an effort to improve the imaging
of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc
cores and gold shells, aiming to render them in vivo visibility through positron
emission tomography (PET) after the proton activation of the zinc core as well as
capability to induce radiosensitization through the secondary electrons produced
from the gold shell when irradiated by various radiation sources. METHODS: Nearly
spherical zinc NPs (~5-nm diameter) were synthesized and then coated with a ~4.25
nm gold layer to make Zn@Au NPs (~13.5-nm total diameter). 28.6 mg of these Zn@Au
NPs was deposited (~100 MUm thick) on a thin cellulose target and placed in an
aluminum target holder and subsequently irradiated with 14.15-MeV protons from a
GE PETtrace cyclotron with 5-MUA current for 5 min. After irradiation, the
cellulose matrix with the NPs was placed in a dose calibrator to assess the
induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma
ray spectroscopy using an high-purity germanium detector was conducted on a very
small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition
to experimental measurements, Monte Carlo simulations were also performed with
radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV
protons and 250-kVp x-rays. RESULTS: The authors measured 168 MUCi of activity 32
min after the end of bombardment for the 14.15-MeV proton energy sample using the
(66)Ga setting on a dose calibrator; activity decreased to 2 MUCi over a 24-h
period. For the 8-MeV proton energy sample, PET imaging was additionally
performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong
peaks at 511 keV (2.05 * 10(6) counts) with several other peaks of smaller
magnitude for each proton energy sample. PET imaging showed strong PET signals
from mostly decaying (66)Ga. The Monte Carlo results showed that radioactive
Zn@Au NPs and solid GNPs provided similar characteristics in terms of their
secondary electron spectra when irradiated. CONCLUSIONS: The Zn@Au NPs developed
in this investigation have the potential to be used as PET-imageable
radiosensitizers for radiotherapy applications as well as PET tracers for
molecular imaging applications.
PMID- 27487896
TI - Technical Report: Evaluation of peripheral dose for flattening filter free photon
beams.
AB - PURPOSE: To develop a comprehensive peripheral dose (PD) dataset for the two
unflattened beams of nominal energy 6 and 10 MV for use in clinical care.
METHODS: Measurements were made in a 40 * 120 * 20 cm(3) (width * length * depth)
stack of solid water using an ionization chamber at varying depths (dmax, 5, and
10 cm), field sizes (3 * 3 to 30 * 30 cm(2)), and distances from the field edge
(5-40 cm). The effects of the multileaf collimator (MLC) and collimator rotation
were also evaluated for a 10 * 10 cm(2) field. Using the same phantom geometry,
the accuracy of the analytic anisotropic algorithm (AAA) and Acuros dose
calculation algorithm was assessed and compared to the measured values. RESULTS:
The PDs for both the 6 flattening filter free (FFF) and 10 FFF photon beams were
found to decrease with increasing distance from the radiation field edge and the
decreasing field size. The measured PD was observed to be higher for the 6 FFF
than for the 10 FFF for all field sizes and depths. The impact of collimator
rotation was not found to be clinically significant when used in conjunction with
MLCs. AAA and Acuros algorithms both underestimated the PD with average errors of
-13.6% and -7.8%, respectively, for all field sizes and depths at distances of 5
and 10 cm from the field edge, but the average error was found to increase to
nearly -69% at greater distances. CONCLUSIONS: Given the known inaccuracies of
peripheral dose calculations, this comprehensive dataset can be used to estimate
the out-of-field dose to regions of interest such as organs at risk, electronic
implantable devices, and a fetus. While the impact of collimator rotation was not
found to significantly decrease PD when used in conjunction with MLCs, results
are expected to be machine model and beam energy dependent. It is not recommended
to use a treatment planning system to estimate PD due to the underestimation of
the out-of-field dose and the inability to calculate dose at extended distances
due to the limits of the dose calculation matrix.
PMID- 27487897
TI - Technical Note: Dose effects of 1.5 T transverse magnetic field on tissue
interfaces in MRI-guided radiotherapy.
AB - PURPOSE: The integration of MRI with a linear accelerator (MR-linac) offers great
potential for high-precision delivery of radiation therapy (RT). However, the
electron deflection resulting from the presence of a transverse magnetic field
(TMF) can affect the dose distribution, particularly the electron return effect
(ERE) at tissue interfaces. The purpose of the study is to investigate the dose
effects of ERE at air-tissue and lung-tissue interfaces during intensity
modulated radiation therapy (IMRT) planning. METHODS: IMRT and volumetric
modulated arc therapy (VMAT) plans for representative pancreas, lung, breast, and
head and neck (HN) cases were generated following commonly used clinical dose
volume (DV) criteria. In each case, three types of plans were generated: (1) the
original plan generated without a TMF; (2) the reconstructed plan generated by
recalculating the original plan with the presence of a TMF of 1.5 T (no
optimization); and (3) the optimized plan generated by a full optimization with
TMF = 1.5 T. These plans were compared using a variety of DV parameters,
including V100%, D95%, DHI [dose heterogeneity index: (D20%-D80%)/Dprescription],
Dmax, and D1cc in OARs (organs at risk) and tissue interface. All the
optimizations and calculations in this work were performed on static data.
RESULTS: The dose recalculation under TMF showed the presence of the 1.5 T TMF
can slightly reduce V100% and D95% for PTV, with the differences being less than
4% for all but one lung case studied. The TMF results in considerable increases
in Dmax and D1cc on the skin in all cases, mostly between 10% and 35%. The
changes in Dmax and D1cc on air cavity walls are dependent upon site, geometry,
and size, with changes ranging up to 15%. The VMAT plans lead to much smaller
dose effects from ERE compared to fixed-beam IMRT in pancreas case. When the TMF
is considered in the plan optimization, the dose effects of the TMF at tissue
interfaces (e.g., air-cavity wall, lung-tissue interfaces, skin) are
significantly reduced in most cases. CONCLUSIONS: The doses on tissue interfaces
can be significantly changed by the presence of a TMF during MR-guided RT when
the magnetic field is not included in plan optimization. These changes can be
substantially reduced or even eliminated during VMAT/IMRT optimization that
specifically considers the TMF, without deteriorating overall plan quality.
PMID- 27487898
TI - Technical Note: Robust measurement of the slice-sensitivity profile in breast
tomosynthesis.
AB - PURPOSE: The purpose of this work is to improve the repeatability of the
measurement of the slice-sensitivity profile (SSP) in reconstructed breast
tomosynthesis volumes. METHODS: A grid of aluminum ball-bearings (BBs) within a
PMMA phantom was imaged on breast tomosynthesis systems from three different
manufacturers. The full-width half-maximum (FWHM) values were measured for the
SSPs of the BBs in the reconstructed volumes. The effect of transforming the
volumes from a Cartesian coordinate system (CCS) to a cone-beam coordinate system
(CBCS) on the variability in the FWHM values was assessed. RESULTS: Transforming
the volumes from a CCS to a CBCS before measuring the SSPs reduced the
coefficient of variation (COV) in the measurements of FWHM in repeated
measurements by 56% and reduced the dependence of the FWHM values on the location
of the BBs within the reconstructed volume by 76%. CONCLUSIONS: Measuring the SSP
in the volumes in a CBCS improves the robustness of the measurement.
PMID- 27487899
TI - Integrated PET/MR breast cancer imaging: Attenuation correction and
implementation of a 16-channel RF coil.
AB - PURPOSE: This study aims to develop, implement, and evaluate a 16-channel
radiofrequency (RF) coil for integrated positron emission tomography/magnetic
resonance (PET/MR) imaging of breast cancer. The RF coil is designed for
optimized MR imaging performance and PET transparency and attenuation correction
(AC) is applied for accurate PET quantification. METHODS: A 16-channel breast
array RF coil was designed for integrated PET/MR hybrid imaging of breast cancer
lesions. The RF coil features a lightweight rigid design and is positioned with a
spacer at a defined position on the patient table of an integrated PET/MR system.
Attenuation correction is performed by generating and applying a dedicated 3D CT
based template attenuation map. Reposition accuracy of the RF coil on the system
patient table while using the positioning frame was tested in repeated
measurements using MR-visible markers. The MR, PET, and PET/MR imaging
performances were systematically evaluated using modular breast phantoms.
Attenuation correction of the RF coil was evaluated with difference measurements
of the active breast phantoms filled with radiotracer in the PET detector with
and without the RF coil in place, serving as a standard of reference measurement.
The overall PET/MR imaging performance and PET quantification accuracy of the new
16-channel RF coil and its AC were then evaluated in first clinical examinations
on ten patients with local breast cancer. RESULTS: The RF breast array coil
provides excellent signal-to-noise ratio and signal homogeneity across the volume
of the breast phantoms in MR imaging and visualizes small structures in the
phantoms down to 0.4 mm in plane. Difference measurements with PET revealed a
global loss and thus attenuation of counts by 13% (mean value across the whole
phantom volume) when the RF coil is placed in the PET detector. Local attenuation
ranging from 0% in the middle of the phantoms up to 24% was detected in the
peripheral regions of the phantoms at positions closer to attenuating hardware
structures of the RF coil. The position accuracy of the RF coil on the patient
table when using the positioning frame was determined well below 1 mm for all
three spatial dimensions. This ensures perfect position match between the RF coil
and its three-dimensional attenuation template during the PET data reconstruction
process. When applying the CT-based AC of the RF coil, the global attenuation
bias was mostly compensated to +/-0.5% across the entire breast imaging volume.
The patient study revealed high quality MR, PET, and combined PET/MR imaging of
breast cancer. Quantitative activity measurements in all 11 breast cancer lesions
of the ten patients resulted in increased mean difference values of SUVmax 11.8%
(minimum 3.2%; maximum 23.2%) between nonAC images and images when AC of the RF
breast coil was applied. This supports the quantitative results of the phantom
study as well as successful attenuation correction of the RF coil. CONCLUSIONS: A
16-channel breast RF coil was designed for optimized MR imaging performance and
PET transparency and was successfully integrated with its dedicated attenuation
correction template into a whole-body PET/MR system. Systematic PET/MR imaging
evaluation with phantoms and an initial study on patients with breast cancer
provided excellent MR and PET image quality and accurate PET quantification.
PMID- 27487900
TI - Technical Note: Evaluation of a 160-mm/256-row CT scanner for whole-heart
quantitative myocardial perfusion imaging.
AB - PURPOSE: The authors investigated the performance of a recently introduced 160
mm/256-row CT system for low dose quantitative myocardial perfusion (MP) imaging
of the whole heart. This platform is equipped with a gantry capable of rotating
at 280 ms per full cycle, a second generation of adaptive statistical iterative
reconstruction (ASiR-V) to correct for image noise arising from low tube voltage
potential/tube current dynamic scanning, and image reconstruction algorithms to
tackle beam-hardening, cone-beam, and partial-scan effects. METHODS: Phantom
studies were performed to investigate the effectiveness of image noise and
artifact reduction with a GE Healthcare Revolution CT system for three
acquisition protocols used in quantitative CT MP imaging: 100, 120, and 140
kVp/25 mAs. The heart chambers of an anthropomorphic chest phantom were filled
with iodinated contrast solution at different concentrations (contrast levels) to
simulate the circulation of contrast through the heart in quantitative CT MP
imaging. To evaluate beam-hardening correction, the phantom was scanned at each
contrast level to measure the changes in CT number (in Hounsfield unit or HU) in
the water-filled region surrounding the heart chambers with respect to baseline.
To evaluate cone-beam artifact correction, differences in mean water HU between
the central and peripheral slices were compared. Partial-scan artifact correction
was evaluated from the fluctuation of mean water HU in successive partial scans.
To evaluate image noise reduction, a small hollow region adjacent to the heart
chambers was filled with diluted contrast, and contrast-to-noise ratio in the
region before and after noise correction with ASiR-V was compared. The quality of
MP maps acquired with the CT system was also evaluated in porcine CT MP studies.
Myocardial infarct was induced in a farm pig from a transient occlusion of the
distal left anterior descending (LAD) artery with a catheter-based interventional
procedure. MP maps were generated from the dynamic contrast-enhanced (DCE) heart
images taken at baseline and three weeks after the ischemic insult. RESULTS:
Their results showed that the phantom and animal images acquired with the CT
platform were minimally affected by image noise and artifacts. For the beam
hardening phantom study, changes in water HU in the wall surrounding the heart
chambers greatly reduced from >+/-30 to <= +/- 5 HU at all kVp settings except
one region at 100 kVp (7 HU). For the cone-beam phantom study, differences in
mean water HU from the central slice were less than 5 HU at two peripheral slices
with each 4 cm away from the central slice. These findings were reproducible in
the pig DCE images at two peripheral slices that were 6 cm away from the central
slice. For the partial-scan phantom study, standard deviations of the mean water
HU in 10 successive partial scans were less than 5 HU at the central slice.
Similar observations were made in the pig DCE images at two peripheral slices
with each 6 cm away from the central slice. For the image noise phantom study,
CNRs in the ASiR-V images were statistically higher (p < 0.05) than the non-ASiR
V images at all kVp settings. MP maps generated from the porcine DCE images were
in excellent quality, with the ischemia in the LAD territory clearly seen in the
three orthogonal views. CONCLUSIONS: The study demonstrates that this CT system
can provide accurate and reproducible CT numbers during cardiac gated
acquisitions across a wide axial field of view. This CT number fidelity will
enable this imaging tool to assess contrast enhancement, potentially providing
valuable added information beyond anatomic evaluation of coronary stenoses.
Furthermore, their results collectively suggested that the 100 kVp/25 mAs
protocol run on this CT system provides sufficient image accuracy at a low
radiation dose (<3 mSv) for whole-heart quantitative CT MP imaging.
PMID- 27487901
TI - Patient positioning in radiotherapy based on surface imaging using time of flight
cameras.
AB - PURPOSE: To evaluate the patient positioning accuracy in radiotherapy using a
stereo-time of flight (ToF)-camera system. METHODS: A system using two ToF
cameras was used to scan the surface of the patients in order to position them
daily on the treatment couch. The obtained point clouds were registered to (a)
detect translations applied to the table (intrafraction motion) and (b) predict
the displacement to be applied in order to place the patient in its reference
position (interfraction motion). The measures provided by this system were
compared to the effectively applied translations. The authors analyzed 150
fractions including lung, pelvis/prostate, and head and neck cancer patients.
RESULTS: The authors obtained small absolute errors for displacement detection:
0.8 +/- 0.7, 0.8 +/- 0.7, and 0.7 +/- 0.6 mm along the vertical, longitudinal,
and lateral axes, respectively, and 0.8 +/- 0.7 mm for the total norm
displacement. Lung cancer patients presented the largest errors with a respective
mean of 1.1 +/- 0.9, 0.9 +/- 0.9, and 0.8 +/- 0.7 mm. CONCLUSIONS: The proposed
stereo-ToF system allows for sufficient accuracy and faster patient repositioning
in radiotherapy. Its capability to track the complete patient surface in real
time could allow, in the future, not only for an accurate positioning but also a
real time tracking of any patient intrafraction motion (translation, involuntary,
and breathing).
PMID- 27487902
TI - Modification and validation of an analytical source model for external beam
radiotherapy Monte Carlo dose calculations.
AB - PURPOSE: A dose calculation tool, which combines the accuracy of the dose
planning method (DPM) Monte Carlo code and the versatility of a practical
analytical multisource model, which was previously reported has been improved and
validated for the Varian 6 and 10 MV linear accelerators (linacs). The
calculation tool can be used to calculate doses in advanced clinical application
studies. One shortcoming of current clinical trials that report dose from patient
plans is the lack of a standardized dose calculation methodology. Because
commercial treatment planning systems (TPSs) have their own dose calculation
algorithms and the clinical trial participant who uses these systems is
responsible for commissioning the beam model, variation exists in the reported
calculated dose distributions. Today's modern linac is manufactured to tight
specifications so that variability within a linac model is quite low. The
expectation is that a single dose calculation tool for a specific linac model can
be used to accurately recalculate dose from patient plans that have been
submitted to the clinical trial community from any institution. The calculation
tool would provide for a more meaningful outcome analysis. METHODS: The
analytical source model was described by a primary point source, a secondary
extra-focal source, and a contaminant electron source. Off-axis energy softening
and fluence effects were also included. The additions of hyperbolic functions
have been incorporated into the model to correct for the changes in output and in
electron contamination with field size. A multileaf collimator (MLC) model is
included to facilitate phantom and patient dose calculations. An offset to the
MLC leaf positions was used to correct for the rudimentary assumed primary point
source. RESULTS: Dose calculations of the depth dose and profiles for field sizes
4 * 4 to 40 * 40 cm agree with measurement within 2% of the maximum dose or 2 mm
distance to agreement (DTA) for 95% of the data points tested. The model was
capable of predicting the depth of the maximum dose within 1 mm. Anthropomorphic
phantom benchmark testing of modulated and patterned MLCs treatment plans showed
agreement to measurement within 3% in target regions using thermoluminescent
dosimeters (TLD). Using radiochromic film normalized to TLD, a gamma criteria of
3% of maximum dose and 2 mm DTA was applied with a pass rate of least 85% in the
high dose, high gradient, and low dose regions. Finally, recalculations of
patient plans using DPM showed good agreement relative to a commercial TPS when
comparing dose volume histograms and 2D dose distributions. CONCLUSIONS: A unique
analytical source model coupled to the dose planning method Monte Carlo dose
calculation code has been modified and validated using basic beam data and
anthropomorphic phantom measurement. While this tool can be applied in general
use for a particular linac model, specifically it was developed to provide a
singular methodology to independently assess treatment plan dose distributions
from those clinical institutions participating in National Cancer Institute
trials.
PMID- 27487903
TI - Variability in CT lung-nodule quantification: Effects of dose reduction and
reconstruction methods on density and texture based features.
AB - PURPOSE: To investigate the effects of dose level and reconstruction method on
density and texture based features computed from CT lung nodules. METHODS: This
study had two major components. In the first component, a uniform water phantom
was scanned at three dose levels and images were reconstructed using four
conventional filtered backprojection (FBP) and four iterative reconstruction (IR)
methods for a total of 24 different combinations of acquisition and
reconstruction conditions. In the second component, raw projection (sinogram)
data were obtained for 33 lung nodules from patients scanned as a part of their
clinical practice, where low dose acquisitions were simulated by adding noise to
sinograms acquired at clinical dose levels (a total of four dose levels) and
reconstructed using one FBP kernel and two IR kernels for a total of 12
conditions. For the water phantom, spherical regions of interest (ROIs) were
created at multiple locations within the water phantom on one reference image
obtained at a reference condition. For the lung nodule cases, the ROI of each
nodule was contoured semiautomatically (with manual editing) from images obtained
at a reference condition. All ROIs were applied to their corresponding images
reconstructed at different conditions. For 17 of the nodule cases, repeat
contours were performed to assess repeatability. Histogram (eight features) and
gray level co-occurrence matrix (GLCM) based texture features (34 features) were
computed for all ROIs. For the lung nodule cases, the reference condition was
selected to be 100% of clinical dose with FBP reconstruction using the B45f
kernel; feature values calculated from other conditions were compared to this
reference condition. A measure was introduced, which the authors refer to as Q,
to assess the stability of features across different conditions, which is defined
as the ratio of reproducibility (across conditions) to repeatability (across
repeat contours) of each feature. RESULTS: The water phantom results demonstrated
substantial variability among feature values calculated across conditions, with
the exception of histogram mean. Features calculated from lung nodules
demonstrated similar results with histogram mean as the most robust feature (Q <=
1), having a mean and standard deviation Q of 0.37 and 0.22, respectively.
Surprisingly, histogram standard deviation and variance features were also quite
robust. Some GLCM features were also quite robust across conditions, namely,
diff. variance, sum variance, sum average, variance, and mean. Except for
histogram mean, all features have a Q of larger than one in at least one of the
3% dose level conditions. CONCLUSIONS: As expected, the histogram mean is the
most robust feature in their study. The effects of acquisition and reconstruction
conditions on GLCM features vary widely, though trending toward features
involving summation of product between intensities and probabilities being more
robust, barring a few exceptions. Overall, care should be taken into account for
variation in density and texture features if a variety of dose and reconstruction
conditions are used for the quantification of lung nodules in CT, otherwise
changes in quantification results may be more reflective of changes due to
acquisition and reconstruction conditions than in the nodule itself.
PMID- 27487904
TI - Resolution recovery for Compton camera using origin ensemble algorithm.
AB - PURPOSE: Compton cameras (CCs) use electronic collimation to reconstruct the
images of activity distribution. Although this approach can greatly improve
imaging efficiency, due to complex geometry of the CC principle, image
reconstruction with the standard iterative algorithms, such as ordered subset
expectation maximization (OSEM), can be very time-consuming, even more so if
resolution recovery (RR) is implemented. We have previously shown that the origin
ensemble (OE) algorithm can be used for the reconstruction of the CC data. Here
we propose a method of extending our OE algorithm to include RR. METHODS: To
validate the proposed algorithm we used Monte Carlo simulations of a CC composed
of multiple layers of pixelated CZT detectors and designed for imaging small
animals. A series of CC acquisitions of small hot spheres and the Derenzo phantom
placed in air were simulated. Images obtained from (a) the exact data, (b)
blurred data but reconstructed without resolution recovery, and (c) blurred and
reconstructed with resolution recovery were compared. Furthermore, the
reconstructed contrast-to-background ratios were investigated using the phantom
with nine spheres placed in a hot background. RESULTS: Our simulations
demonstrate that the proposed method allows for the recovery of the resolution
loss that is due to imperfect accuracy of event detection. Additionally, tests of
camera sensitivity corresponding to different detector configurations demonstrate
that the proposed CC design has sensitivity comparable to PET. When the same
number of events were considered, the computation time per iteration increased
only by a factor of 2 when OE reconstruction with the resolution recovery
correction was performed relative to the original OE algorithm. We estimate that
the addition of resolution recovery to the OSEM would increase reconstruction
times by 2-3 orders of magnitude per iteration. CONCLUSIONS: The results of our
tests demonstrate the improvement of image resolution provided by the OE
reconstructions with resolution recovery. The quality of images and their
contrast are similar to those obtained from the OE reconstructions from scans
simulated with perfect energy and spatial resolutions.
PMID- 27487905
TI - Image quality comparison between single energy and dual energy CT protocols for
hepatic imaging.
AB - PURPOSE: Multi-detector computed tomography (MDCT) enables volumetric scans in a
single breath hold and is clinically useful for hepatic imaging. For simple
tasks, conventional single energy (SE) computed tomography (CT) images acquired
at the optimal tube potential are known to have better quality than dual energy
(DE) blended images. However, liver imaging is complex and often requires imaging
of both structures containing iodinated contrast media, where atomic number
differences are the primary contrast mechanism, and other structures, where
density differences are the primary contrast mechanism. Hence it is conceivable
that the broad spectrum used in a dual energy acquisition may be an advantage. In
this work we are interested in comparing these two imaging strategies at equal
dose and more complex settings. METHODS: We developed numerical anthropomorphic
phantoms to mimic realistic clinical CT scans for medium size and large size
patients. MDCT images based on the defined phantoms were simulated using various
SE and DE protocols at pre- and post-contrast stages. For SE CT, images from 60
kVp through 140 with 10 kVp steps were considered; for DE CT, both 80/140 and
100/140 kVp scans were simulated and linearly blended at the optimal weights. To
make a fair comparison, the mAs of each scan was adjusted to match the reference
radiation dose (120 kVp, 200 mAs for medium size patients and 140 kVp, 400 mAs
for large size patients). Contrast-to-noise ratio (CNR) of liver against other
soft tissues was used to evaluate and compare the SE and DE protocols, and
multiple pre- and post-contrasted liver-tissue pairs were used to define a
composite CNR. To help validate the simulation results, we conducted a small
clinical study. Eighty-five 120 kVp images and 81 blended 80/140 kVp images were
collected and compared through both quantitative image quality analysis and an
observer study. RESULTS: In the simulation study, we found that the CNR of pre
contrast SE image mostly increased with increasing kVp while for post-contrast
imaging 90 kVp or lower yielded higher CNR images, depending on the differential
iodine concentration of each tissue. Similar trends were seen in DE blended CNR
and those from SE protocols. In the presence of differential iodine concentration
(i.e., post-contrast), the CNR curves maximize at lower kVps (80-120), with the
peak shifted rightward for larger patients. The combined pre- and post-contrast
composite CNR study demonstrated that an optimal SE protocol has better
performance than blended DE images, and the optimal tube potential for SE scan is
around 90 kVp for a medium size patients and between 90 and 120 kVp for large
size patients (although low kVp imaging requires high x-ray tube power to avoid
photon starvation). Also, a tin filter added to the high kVp beam is not only
beneficial for material decomposition but it improves the CNR of the DE blended
images as well. The dose adjusted CNR of the clinical images also showed the same
trend and radiologists favored the SE scans over blended DE images. CONCLUSIONS:
Our simulation showed that an optimized SE protocol produces up to 5% higher CNR
for a range of clinical tasks. The clinical study also suggested 120 kVp SE scans
have better image quality than blended DE images. Hence, blended DE images do not
have a fundamental CNR advantage over optimized SE images.
PMID- 27487906
TI - Delivered dose uncertainty analysis at the tumor apex for ocular brachytherapy.
AB - PURPOSE: To estimate the total dosimetric uncertainty at the tumor apex for
ocular brachytherapy treatments delivered using 16 mm Collaborative Ocular
Melanoma Study (COMS) and Super9 plaques loaded with (125)I seeds in order to
determine the size of the apex margin that would be required to ensure adequate
dosimetric coverage of the tumor. METHODS: The total dosimetric uncertainty was
assessed for three reference tumor heights: 3, 5, and 10 mm, using the Guide to
the expression of Uncertainty in Measurement/National Institute of Standards and
Technology approach. Uncertainties pertaining to seed construction, source
strength, plaque assembly, treatment planning calculations, tumor height
measurement, plaque placement, and plaque tilt for a simple dome-shaped tumor
were investigated and quantified to estimate the total dosimetric uncertainty at
the tumor apex. Uncertainties in seed construction were determined using EBT3
Gafchromic film measurements around single seeds, plaque assembly uncertainties
were determined using high resolution microCT scanning of loaded plaques to
measure seed positions in the plaques, and all other uncertainties were
determined from the previously published studies and recommended values. All dose
calculations were performed using plaque simulator v5.7.6 ophthalmic treatment
planning system with the inclusion of plaque heterogeneity corrections. RESULTS:
The total dosimetric uncertainties at 3, 5, and 10 mm tumor heights for the 16 mm
COMS plaque were 17.3%, 16.1%, and 14.2%, respectively, and for the Super9 plaque
were 18.2%, 14.4%, and 13.1%, respectively (all values with coverage factor k =
2). The apex margins at 3, 5, and 10 mm tumor heights required to adequately
account for these uncertainties were 1.3, 1.3, and 1.4 mm, respectively, for the
16 mm COMS plaque, and 1.8, 1.4, and 1.2 mm, respectively, for the Super9 plaque.
These uncertainties and associated margins are dependent on the dose gradient at
the given prescription depth, thus resulting in the changing uncertainties and
margins with depth. CONCLUSIONS: The margins determined in this work can be used
as a guide for determining an appropriate apex margin for a given treatment,
which can be chosen based on the tumor height. The required margin may need to be
increased for more complex scenarios (mushroom shaped tumors, tumors close to the
optic nerve, oblique muscle related tilt, etc.) than the simple dome-shaped tumor
examined and should be chosen on a case-by-case basis. The sources of uncertainty
contributing most significantly to the total dosimetric uncertainty are seed
placement within the plaques, treatment planning calculations, tumor height
measurement, and plaque tilt. This work presents an uncertainty-based, rational
approach to estimating an appropriate apex margin.
PMID- 27487907
TI - CNR considerations for rapid real-time MRI tumor tracking in radiotherapy hybrid
devices: Effects of B0 field strength.
AB - PURPOSE: This work examines the subject of contrast-to-noise ratio (CNR),
specifically between tumor and tissue background, and its dependence on the MRI
field strength, B0. This examination is motivated by the recent interest and
developments in MRI/radiotherapy hybrids where real-time imaging can be used to
guide treatment beams. The ability to distinguish a tumor from background tissue
is of primary importance in this field, and this work seeks to elucidate the
complex relationship between the CNR and B0 that is too often assumed to be
purely linear. METHODS: Experimentally based models of B0-dependant relaxation
for various tumor and normal tissues from the literature were used in conjunction
with signal equations for MR sequences suitable for rapid real-time imaging to
develop field-dependent predictions for CNR. These CNR models were developed for
liver, lung, breast, glioma, and kidney tumors for spoiled gradient-echo,
balanced steady-state free precession (bSSFP), and single-shot half-Fourier fast
spin echo sequences. RESULTS: Due to the pattern in which the relaxation
properties of tissues are found to vary over B0 field (specifically the T1 time),
there was always an improved CNR at lower fields compared to linear dependency.
Further, in some tumor sites, the CNR at lower fields was found to be comparable
to, or sometimes higher than those at higher fields (i.e., bSSFP CNR for glioma,
kidney, and liver tumors). CONCLUSIONS: In terms of CNR, lower B0 fields have
been shown to perform as well or better than higher fields for some tumor sites
due to superior T1 contrast. In other sites this effect was less pronounced,
reversing the CNR advantage. This complex relationship between CNR and B0 reveals
both low and high magnetic fields as viable options for tumor tracking in
MRI/radiotherapy hybrids.
PMID- 27487908
TI - Reference dosimetry in magnetic fields: formalism and ionization chamber
correction factors.
AB - PURPOSE: Magnetic resonance imaging-guided radiotherapy (MRIgRT) provides
superior soft-tissue contrast and real-time imaging compared with standard image
guided RT, which uses x-ray based imaging. Several groups are developing
integrated MRIgRT machines. Reference dosimetry with these new machines requires
accounting for the effects of the magnetic field on the response of the
ionization chambers used for dose calibration. Here, the authors propose a
formalism for reference dosimetry with integrated MRIgRT devices. The authors
also examined the suitability of the TPR10 (20) and %dd(10)x beam quality
specifiers in the presence of magnetic fields and calculated detector correction
factors to account for the effects of the magnetic field for a range of
detectors. METHODS: The authors used full-head and point-source Monte Carlo
models of an MR-linac along with detailed detector models of an Exradin A19, an
NE2571, and several PTW Farmer chambers to calculate magnetic field correction
factors for six commercial ionization chambers in three chamber configurations.
Calculations of ionization chamber response (performed with geant4) were
validated with specialized Fano cavity tests. %dd(10)x values, TPR10 (20) values,
and Spencer-Attix water-to-air restricted stopping power ratios were also
calculated. The results were further validated against measurements made with a
preclinical functioning MR-linac. RESULTS: The TPR10 (20) was found to be
insensitive to the presence of the magnetic field, whereas the relative change in
%dd(10)x was 2.4% when a transverse 1.5 T field was applied. The parameters
chosen for the ionization chamber calculations passed the Fano cavity test to
within ~0.1%. Magnetic field correction factors varied in magnitude with detector
orientation with the smallest corrections found when the chamber was parallel to
the magnetic field. CONCLUSIONS: Reference dosimetry can be performed with
integrated MRIgRT devices by using magnetic field correction factors, but care
must be taken with the choice of beam quality specifier and chamber orientation.
The uncertainties achievable under this formalism should be similar to those of
conventional formalisms, although this must be further quantified.
PMID- 27487909
TI - Transversus abdominis plane block after laparoscopic colonic resection in cancer
patients: A randomised clinical trial.
AB - BACKGROUND: A key point in pathways for optimal rehabilitation and enhanced
recovery is an effective postoperative multimodal pain treatment regimen.
OBJECTIVE: To investigate the analgesic effects of transversus abdominis plane
(TAP) block in conjunction with paracetamol and ibuprofen in patients undergoing
laparoscopic colonic resection. DESIGN: Randomised placebo-controlled double
blind study. SETTING: Herlev University Hospital, Copenhagen, Denmark, from March
2010 to February 2013. PATIENTS: Eighty adult patients scheduled for elective
laparoscopic colectomy. INTERVENTIONS: Bilateral TAP block with 20 ml of either
ropivacaine or isotonic saline. MAIN OUTCOME MEASURES: Visual analogue scale
(VAS) pain scores (0 to 100 mm) while coughing at 6 h after surgery (primary
outcome). Secondary outcomes were area under the curve pain scores (2 to 24 h) at
rest and while coughing, 24-h morphine consumption and incidence of nausea and
vomiting. RESULTS: VAS pain scores at 6 h while coughing was not different
between groups (median, interquartile range), TAP, 27 (11 to 45) mm vs. placebo,
33 (20 to 49) mm (P = 0.20). Total 24-h morphine consumption was reduced in the
TAP block group vs. placebo group, 30 (15 to 41) mg vs. 43 (30 to 67) mg,
respectively (P = 0.008). This difference was most pronounced in the first
postoperative hours. The remaining outcomes did not differ between groups.
CONCLUSION: TAP block used in combination with paracetamol and ibuprofen did not
reduce pain after laparoscopic colonic surgery. However, we found a 30% reduction
in opioid use, most marked in the early postoperative period. TRIAL REGISTRATION:
www.clinicaltrials.gov (NCT01418144).
PMID- 27487910
TI - Implementation of patient blood management remains extremely variable in Europe
and Canada: the NATA benchmark project: An observational study.
AB - BACKGROUND: Preoperative anaemia is associated with increased postoperative
morbidity and mortality. Patient blood management (PBM) is advocated to improve
patient outcomes. OBJECTIVES: NATA, the 'Network for the advancement of patient
blood management, haemostasis and thrombosis', initiated a benchmark project with
the aim of providing the basis for educational strategies to implement optimal
PBM in participating centres. DESIGN: Prospective, observational study with
online data collection in 11 secondary and tertiary care institutions interested
in developing PBM. SETTING: Ten European centres (Austria, Spain, England,
Denmark, Belgium, Netherlands, Romania, Greece, France, and Germany) and one
Canadian centre participated between January 2010 and June 2011. PATIENTS: A
total of 2470 patients undergoing total hip (THR) or knee replacement, or
coronary artery bypass grafting (CABG), were registered in the study. Data from
2431 records were included in the final analysis. MAIN OUTCOME MEASURES: Primary
outcome measures were the incidence and volume of red blood cells (RBC)
transfused. Logistic regression analysis identified variables independently
associated with RBC transfusions. RESULTS: The incidence of transfusion was
significantly different between centres for THR (range 7 to 95%), total knee
replacement (range 3 to 100%) and CABG (range 20 to 95%). The volume of RBC
transfused was significantly different between centres for THR and CABG. The
incidence of preoperative anaemia ranged between 3 and 40% and its treatment
between 0 and 40%, the latter not being related to the former. Patient
characteristics, evolution of haemoglobin concentrations and blood losses were
also different between centres. Variables independently associated with RBC
transfusion were preoperative haemoglobin concentration, lost volume of RBC and
female sex. CONCLUSION: Implementation of PBM remains extremely variable across
centres. The relative importance of factors explaining RBC transfusion differs
across institutions, some being patient related whereas others are related to the
healthcare process. The results reported confidentially to each centre will allow
them to implement tailored measures to improve their PBM strategies.
PMID- 27487911
TI - Suberanilohydroxamic acid (vorinostat) synergistically enhances the cytotoxicity
of doxorubicin and cisplatin in osteosarcoma cell lines.
AB - Osteosarcoma is the most common primary bone cancer in children and is a highly
malignant disease, in which 25% of patients present with metastasis at diagnosis.
Considerable advances in the treatment of localized disease have been achieved
since the introduction of combined modality treatment, increasing the prognosis
of overall survival to 70%. Yet, established therapies have only limited success
in treating both metastatic disease and nonresponders to primary chemotherapy.
Therefore, new therapeutic approaches are required, particularly for the control
of osteosarcoma in these patient groups. Epigenetically modifying substances are
a class of emerging drugs that have shown therapeutic potential in various
hematological and solid cancers. We examined the cytotoxic effects of 5
azacitidine, 3-deazaneplanocin A, and suberanilohydroxamic acid (SAHA) on
osteosarcoma cell lines HOS, MG-63, MNNG, and ZK-58. SAHA was the only chemical
agent that exerted a strong, growth-limiting effect in all cell lines tested. The
growth-limiting effect of SAHA was accompanied by features characteristic of
apoptotic death. We found that cotreatment with SAHA and cisplatin showed strong
synergism in all cell lines. The effect of cotreatment with SAHA and doxorubicin
was cell line dependent. In the cell lines HOS, MG-63, and MNNG, the combined
effect was synergistic, whereas in the cell line ZK-58, SAHA antagonized
doxorubicin. The strong synergism of SAHA indicated that in combination with
cisplatin, it might enable a promising add-on to current therapy regimens.
However, considering the cell line-dependent effect that was found when SAHA was
combined with doxorubicin, further experimentation is needed.
PMID- 27487912
TI - A Simple and Robust Bedside Model for Mortality Risk in Pediatric Patients With
Acute Respiratory Distress Syndrome.
AB - OBJECTIVES: Despite declining mortality, acute respiratory distress syndrome is
still involved in up to one third of pediatric intensive care deaths. The
recently convened Pediatric Acute Lung Injury Consensus Conference has outlined
research priorities for the field, which include the need for accurate bedside
risk stratification of patients. We aimed to develop a simple yet robust model of
mortality risk among pediatric patients with acute respiratory distress syndrome
to facilitate the targeted application of high-risk investigational therapies and
stratification for enrollment in clinical trials. DESIGN: Prospective,
multicenter cohort. SETTING: Five academic PICUs. PATIENTS: Three hundred eight
children greater than 1 month and less than or equal to 18 years old, admitted to
the ICU, with bilateral infiltrates on chest radiograph and PaO2/FIO2 ratio less
than 300 in the clinical absence of left atrial hypertension. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Twenty clinical variables were recorded in
the following six categories: demographics, medical history, oxygenation,
ventilation, radiographic imaging, and multiple organ dysfunction. Data were
measured 0-24 and 48-72 hours after acute respiratory distress syndrome onset
(day 1 and 3) and examined for associations with hospital mortality. Among 308
enrolled patients, mortality was 17%. Children with a history of cancer and/or
hematopoietic stem cell transplant had higher mortality (47% vs 11%; p < 0.001).
Oxygenation index, the PaO2/FIO2 ratio, extrapulmonary organ dysfunction,
Pediatric Risk of Mortality-3, and positive cumulative fluid balance were each
associated with mortality. Using two statistical approaches, we found that a
parsimonious model of mortality risk using only oxygenation index and
cancer/hematopoietic stem cell transplant history performed as well as other more
complex models that required additional variables. CONCLUSIONS: In the PICU,
oxygenation index and cancer/hematopoietic stem cell transplant history can be
used on acute respiratory distress syndrome day 1 or day 3 to predict hospital
mortality without the need for more complex models. These findings may simplify
risk assessment for clinical trials, counseling families, and high-risk
interventions such as extracorporeal life support.
PMID- 27487913
TI - Bedside Ultrasound for Tracheal Tube Verification in Pediatric Emergency
Department and ICU Patients: A Systematic Review.
AB - OBJECTIVES: Improper placement of the tracheal tube during intubation can lead to
dangerous complications, and bedside ultrasound has been proposed as a method of
quickly and accurately identifying tube placement. Recent studies in adults have
found it to be accurate, but its applicability in pediatric patients is unclear.
This systematic review aims to describe the current available data on the
accuracy and feasibility of bedside ultrasound for tracheal tube placement in
children. DATA SOURCES: OVID MEDLINE and EMBASE. STUDY SELECTION: Available
articles on bedside neck or lung/diaphragm ultrasound for confirmation of
tracheal tube placement in children through December 2015. DATA EXTRACTION: Two
reviewers screened studies for eligibility and abstracted data independently. The
quality of selected articles was evaluated using Quality Assessment of Diagnostic
Accuracy Studies statement. DATA SYNTHESIS: A total of nine articles were
identified: one study using neck ultrasound, two using lung/diaphragmatic
ultrasound, one with both, and five studies looking at direct visualization of
the tracheal tube tip met our inclusion criteria. There were 81 intubations
evaluated using neck ultrasound, 214 intubations evaluated using diaphragmatic or
pleural sliding, and 165 intubations evaluated for feasibility of bedside
ultrasound in visualizing tracheal tube tip placement. The sensitivities of
transtracheal ultrasound for intubation were overall high ranging from 0.92 to
1.00 with excellent specificities at 1.00. For lung ultrasound, the sensitivities
for tracheal placement versus esophageal placement were high at 1.00, but only
one study reported esophageal intubations and had a specificity of 1.00. When
assessing the appropriate tracheal tube depth for tracheal intubations using lung
ultrasound, the sensitivities ranged from 0.91 to 1.00 with specificities ranging
from 0.5 to 1.0. Regarding feasibility of direct visualization of tracheal tube
tip, visualization ranged from 83% to 100%. CONCLUSION: Bedside ultrasound has
been described to be feasible in determining tracheal tube placement in several
small single center studies and could be a useful adjunct tool in confirming
tracheal tube placement in critically ill pediatric patients, but further studies
are needed to assess its accuracy in a randomized multicenter setting.
PMID- 27487914
TI - High-Volume Hemofiltration in Critically Ill Patients With Secondary
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome: A Prospective
Study in the PICU.
AB - OBJECTIVES: Hemophagocytic lymphohistiocytosis, which includes primary (familial)
and secondary hemophagocytic lymphohistiocytosis, is a fatal disease in children.
Macrophage activation syndrome was defined in patients who met secondary
hemophagocytic lymphohistiocytosis criteria with an underlying autoimmune
disease. High-volume hemofiltration has shown beneficial effects in severe sepsis
and multiple organ dysfunction syndrome. Secondary hemophagocytic
lymphohistiocytosis/macrophage activation syndrome shares many pathophysiologic
similarities with sepsis. The present study assessed the effects of high-volume
hemofiltration in children with secondary hemophagocytic
lymphohistiocytosis/macrophage activation syndrome. DESIGN: A single-center
nonrandomized concurrent control trial. SETTING: The PICU of Shanghai Children's
Hospital, Shanghai Jiao Tong University. PATIENTS: Thirty-three critically ill
secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome
patients treated between January 2010 and December 2014. INTERVENTIONS: Thirty
three patients were divided into two groups: high-volume hemofiltration +
hemophagocytic lymphohistiocytosis-2004 group (17 cases) or hemophagocytic
lymphohistiocytosis-2004 group (16 cases). High-volume hemofiltration was defined
as an ultrafiltrate flow rate of 50-70 mL/kg/hr. Clinical and biological
variables were assessed before initiation and after 48 and 72 hours of high
volume hemofiltration therapy. MEASUREMENTS AND MAIN RESULTS: The total mortality
rate was 42.4% (14/33), but mortality at 28 days was not significantly different
between the two groups (high-volume hemofiltration + hemophagocytic
lymphohistiocytosis-2004 group: five deaths, 29.4%; hemophagocytic
lymphohistiocytosis-2004 group: nine deaths, 56.3%; chi-square, 2.431; p =
0.119). Children received high-volume hemofiltration for 60.2 +/- 42.0 hours.
After 48 and 72 hours respectively, a significant decrease in serum ferritin (p <
0.001), aspartate aminotransferase (p = 0.037 and p < 0.001), total bilirubin (p
= 0.041 and p = 0.037), and serum creatinine (p = 0.006 and p = 0.004) levels
were observed. Furthermore, the natural killer-cell activity up-regulated (p =
0.047) after 72 hours. Furthermore, significantly decreased levels of serum tumor
necrosis factor-alpha (from 91.5 +/- 44.7 ng/L at 48 hr to 36.7 +/- 24.9 ng/L at
72 hr; p = 0.007)) and interleukin-6 (from 46.9 +/- 21.1 ng/L at 48 hr to 27.7 +/
14.5 ng/L at 72 hr; p < 0.0001) were observed. After 7 days, patients receiving
high-volume hemofiltration had significantly lower bilirubin, creatinine,
ferritin, procalcitonin, lactate dehydrogenase level, tumor necrosis factor
alpha, and interleukin-6 levels, and needed less mechanical ventilation compared
with hemophagocytic lymphohistiocytosis-2004 group patients. No serious adverse
events were observed. CONCLUSIONS: High-volume hemofiltration may improve organ
function by decreasing cytokine levels (tumor necrosis factor-alpha and
interleukin-6). High-volume hemofiltration may be an effective adjunctive
treatment in secondary hemophagocytic lymphohistiocytosis/macrophage activation
syndrome.
PMID- 27487915
TI - Evolution of a G protein-coupled receptor response by mutations in regulatory
network interactions.
AB - All cellular functions depend on the concerted action of multiple proteins
organized in complex networks. To understand how selection acts on protein
networks, we used the yeast mating receptor Ste2, a pheromone-activated G protein
coupled receptor, as a model system. In Saccharomyces cerevisiae, Ste2 is a hub
in a network of interactions controlling both signal transduction and signal
suppression. Through laboratory evolution, we obtained 21 mutant receptors
sensitive to the pheromone of a related yeast species and investigated the
molecular mechanisms behind this newfound sensitivity. While some mutants show
enhanced binding affinity to the foreign pheromone, others only display weakened
interactions with the network's negative regulators. Importantly, the latter
changes have a limited impact on overall pathway regulation, despite their
considerable effect on sensitivity. Our results demonstrate that a new receptor
ligand pair can evolve through network-altering mutations independently of
receptor-ligand binding, and suggest a potential role for such mutations in
disease.
PMID- 27487916
TI - A mixed grape and blueberry extract is safe for dogs to consume.
AB - BACKGROUND: Grape and blueberry extracts are known to protect against age-related
cognitive decline. However, beneficial effects achieved by mixing grape and
blueberry extracts have yet to be evaluated in dogs, or their bioavailability
assessed. Of concern to us were cases of acute renal failure in dogs, after their
ingestion of grapes or raisins. The European Pet Food Industry Federation (2013)
considers only the grape or raisin itself to be potentially dangerous; grape-seed
extracts per-se, are not considered to be a threat. Our aim was therefore to
evaluate the renal and hepatic safety, and measure plasma derivatives of a
polyphenol-rich extract from grape and blueberry (PEGB; from the Neurophenols
Consortium) in dogs. Polyphenol expression was analyzed by UHPLC-MS/MS over 8
hours, for dogs given PEGB at 4 mg/kg. Safety was evaluated using four groups of
6 dogs. These groups received capsules containing no PEGB (control), or PEGB at
4, 20, or 40 mg/kg BW/d, for 24 weeks. Blood and urine samples were taken the
week prior to study commencement, then at the end of the 24-wk study period.
Routine markers of renal and liver damage, including creatinine (Creat), blood
urea nitrogen, albumin, minerals, alkaline phosphatase (ALP), and alanine
transaminase (ALT) were measured. Biomarkers for early renal damage were also
evaluated in plasma (cystatin C (CysC), and neutrophil gelatinase-associated
lipocalin (NGAL)), and urine (CysC, clusterin (Clu), and NGAL). Ratios of urinary
biomarkers to Creat were calculated, and compared with acceptable maximal values
obtained for healthy dogs, as reported in the literature. RESULTS: While several
PEGB-specific polyphenols and metabolites were detected in dog plasma, at the end
of the PEGB consumption period, our biomarker analyses presented no evidence of
either renal or liver damage (Creat, BUN, ionogram, albumin and ALT, ALP).
Similarly, no indication of early renal damage could be detected. Plasma CysC,
urinary CysC/Creat, Clu/Creat, and NGAL/Creat ratios were all beneath reported
benchmarked maximums, with no evidence of PEGB toxicity. CONCLUSIONS: Long-term
consumption of a pet specific blend of a polyphenol-rich extract from grape and
blueberry (PEGB; from the Neurophenols Consortium), was not associated with renal
or hepatic injury, and can therefore be considered safe.
PMID- 27487917
TI - Thermal fluctuations affect the transcriptome through mechanisms independent of
average temperature.
AB - Terrestrial ectotherms are challenged by variation in both mean and variance of
temperature. Phenotypic plasticity (thermal acclimation) might mitigate adverse
effects, however, we lack a fundamental understanding of the molecular mechanisms
of thermal acclimation and how they are affected by fluctuating temperature. Here
we investigated the effect of thermal acclimation in Drosophila melanogaster on
critical thermal maxima (CTmax) and associated global gene expression profiles as
induced by two constant and two ecologically relevant (non-stressful) diurnally
fluctuating temperature regimes. Both mean and fluctuation of temperature
contributed to thermal acclimation and affected the transcriptome. The
transcriptomic response to mean temperatures comprised modification of a major
part of the transcriptome, while the response to fluctuations affected a much
smaller set of genes, which was highly independent of both the response to a
change in mean temperature and to the classic heat shock response. Although the
independent transcriptional effects caused by fluctuations were relatively small,
they are likely to contribute to our understanding of thermal adaptation. We
provide evidence that environmental sensing, particularly phototransduction, is a
central mechanism underlying the regulation of thermal acclimation to fluctuating
temperatures. Thus, genes and pathways involved in phototransduction are likely
of importance in fluctuating climates.
PMID- 27487918
TI - Cu2O Photocathode for Low Bias Photoelectrochemical Water Splitting Enabled by
NiFe-Layered Double Hydroxide Co-Catalyst.
AB - Layered double hydroxides (LDHs) are bimetallic hydroxides that currently attract
considerable attention as co-catalysts in photoelectrochemical (PEC) systems in
view of water splitting under solar light. A wide spectrum of LDHs can be easily
prepared on demand by tuning their chemical composition and structural
morphology. We describe here the electrochemical growth of NiFe-LDH overlayers on
Cu2O electrodes and study their PEC behavior. By using the modified Cu2O/NiFe-LDH
electrodes we observe a remarkable seven-fold increase of the photocurrent
intensity under an applied voltage as low as -0.2 V vs Ag/AgCl. The origin of
such a pronounced effect is the improved electron transfer towards the
electrolyte brought by the NiFe-LDH overlayer due to an appropriate energy level
alignment. Long-term photostability tests reveal that Cu2O/NiFe-LDH photocathodes
show no photocurrent loss after 40 hours of operation under light at -0.2 V vs
Ag/AgCl low bias condition. These improved performances make Cu2O/NiFe-LDH a
suitable photocathode material for low voltage H2 production. Indeed, after 8
hours of H2 production under -0.2 V vs Ag/AgCl the PEC cell delivers a 78%
faradaic efficiency. This unprecedented use of Cu2O/NiFe-LDH as an efficient
photocathode opens new perspectives in view of low biasd or self-biased PEC water
splitting under sunlight illumination.
PMID- 27487919
TI - Fanconi-Bickel syndrome in two Palestinian children: marked phenotypic
variability with identical mutation.
AB - BACKGROUND: Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare autosomal
recessive disease caused by a deficiency of glucose transporter 2 (GLUT2), a
member of the facilitative glucose transporter family (Santer et al. J Inherit
Metab Dis 21:191-194, 1998). The typical clinical picture is characterized by
hepatorenal glycogen accumulation resulting in hepato- and nephromegaly, impaired
utilization of glucose and galactose, proximal renal tubular dysfunction, rickets
and severe short stature. CASE PRESENTATION: We report 2 Palestinian patients
from 2 families who were homozygous for the mutation p.R301X (C>T) in exon 7of
GLUT2 gene. Patient 1 showed clinical and laboratory improvement with age
characterized by normal growth and resolution of rickets. Patient 2 had severe
phenotype characterized by progressive weight loss, persistent metabolic
acidosis, marked polyuria and clinical and laboratory findings of rickets
progressing to death at age 10 months. CONCLUSION: This report further expands
the clinical spectrum of FBS even with identical mutations. Other yet unknown
genetic, environmental or stochastic factors may be responsible for phenotypic
variability.
PMID- 27487920
TI - Crystal structure of the PAS domain of the hEAG potassium channel.
AB - KCNH voltage-gated potassium channels play critical roles in regulating cellular
functions. The channel is composed of four subunits, each of which contains six
transmembrane helices forming the central pore. The cytoplasmic parts of the
subunits present a Per-Arnt-Sim (PAS) domain at the N-terminus and a cyclic
nucleotide-binding homology domain at the C-terminus. PAS domains are conserved
from prokaryotes to eukaryotes and are involved in sensing signals and cellular
responses. To better understand the functional roles of PAS domains in KCNH
channels, the structure of this domain from the human ether-a-go-go channel (hEAG
channel) was determined. By comparing it with the structures of the Homo sapiens
EAG-related gene (hERG) channel and the Drosophila EAG-like K(+) (dELK) channel
and analyzing the structural features of the hEAG channel, it was identified that
a hydrophobic patch on the beta-sheet may mediate interaction between the PAS
domain and other regions of the channel to regulate its functions.
PMID- 27487921
TI - Envelope protein VP24 from White spot syndrome virus: expression, purification
and crystallization.
AB - White spot syndrome virus (WSSV) is a major shrimp pathogen known to infect
penaeid shrimp and other crustaceans. VP24 is one of the major envelope proteins
of WSSV. In order to facilitate purification, crystallization and structure
determination, the predicted N-terminal transmembrane region of approximately 26
amino acids was truncated from VP24 and several mutants were prepared to increase
the proportion of selenomethionine (SeMet) residues for subsequent structural
determination using the SAD method. Truncated VP24, its mutants and the
corresponding SeMet-labelled proteins were purified, and the native and SeMet
proteins were crystallized by the hanging-drop vapour-diffusion method. Crystals
of VP24 were obtained using a reservoir consisting of 0.1 M Tris-HCl pH 8.5, 2.75
M ammonium acetate with a drop volume ratio of two parts protein solution to one
part reservoir solution. Notably, ATP was added as a critical additive to the
drop with a final concentration of 10 mM. Crystals of SeMet-labelled VP24 mutant
diffracted to 3.0 A resolution and those of the native diffracted to 2.4 A
resolution; the crystals belonged to space group I213, with unit-cell parameters
a = b = c = 140 A.
PMID- 27487922
TI - Malonate in the nucleotide-binding site traps human AKAP18gamma/delta in a novel
conformational state.
AB - A-kinase anchoring proteins (AKAPs) are a family of proteins that provide
spatiotemporal resolution of protein kinase A (PKA) phosphorylation. In the
myocardium, PKA and AKAP18gamma/delta are found in complex with sarcoendoplasmic
reticulum Ca(2+)-ATPase 2 (SERCA2) and phospholamban (PLB). This macromolecular
complex provides a means by which anchored PKA can dynamically regulate
cytoplasmic Ca(2+) release and re-uptake. For this reason, AKAP18gamma/delta
presents an interesting drug target with therapeutic potential in cardiovascular
disease. The crystal structure of the central domain of human AKAP18gamma has
been determined at the atomic resolution of 1.25 A. This first structure of human
AKAP18gamma is trapped in a novel conformation by a malonate molecule bridging
the important R-loop with the 2H phosphoesterase motif. Although the
physiological substrate of AKAP18gamma is currently unknown, a potential proton
wire deep in the central binding crevice has been indentified, leading to bulk
solvent below the R-loop. Malonate complexed with AKAP18gamma at atomic
resolution provides an excellent starting point for structure-guided drug design.
PMID- 27487923
TI - Structure of the human DNA-repair protein RAD52 containing surface mutations.
AB - The Rad52 protein is a eukaryotic single-strand DNA-annealing protein that is
involved in the homologous recombinational repair of DNA double-strand breaks.
The isolated N-terminal half of the human RAD52 protein (RAD52(1-212)) forms an
undecameric ring structure with a surface that is mostly positively charged. In
the present study, it was found that RAD52(1-212) containing alanine mutations of
the charged surface residues (Lys102, Lys133 and Glu202) is highly amenable to
crystallization. The structure of the mutant RAD52(1-212) was solved at 2.4 A
resolution. The structure revealed an association between the symmetry-related
RAD52(1-212) rings, in which a partially unfolded, C-terminal region of RAD52
extended into the DNA-binding groove of the neighbouring ring in the crystal. The
alanine mutations probably reduced the surface entropy of the RAD52(1-212) ring
and stabilized the ring-ring association observed in the crystal.
PMID- 27487924
TI - Crystallization and X-ray diffraction analysis of an L-arabinonate dehydratase
from Rhizobium leguminosarum bv. trifolii and a D-xylonate dehydratase from
Caulobacter crescentus.
AB - L-Arabinonate dehydratase (EC 4.2.1.25) and D-xylonate dehydratase (EC 4.2.1.82)
are two enzymes that are involved in a nonphosphorylative oxidation pathway of
pentose sugars. L-Arabinonate dehydratase converts L-arabinonate into 2-dehydro-3
deoxy-L-arabinonate, and D-xylonate dehydratase catalyzes the dehydration of D
xylonate to 2-dehydro-3-deoxy-D-xylonate. L-Arabinonate and D-xylonate
dehydratases belong to the IlvD/EDD family, together with 6-phosphogluconate
dehydratases and dihydroxyacid dehydratases. No crystal structure of any L
arabinonate or D-xylonate dehydratase is available in the PDB. In this study,
recombinant L-arabinonate dehydratase from Rhizobium leguminosarum bv. trifolii
(RlArDHT) and D-xylonate dehydratase from Caulobacter crescentus (CcXyDHT) were
heterologously expressed in Escherichia coli and purified by the use of affinity
chromatography followed by gel-filtration chromatography. The purified proteins
were crystallized using the hanging-drop vapour-diffusion method at 293 K.
Crystals of RlArDHT that diffracted to 2.40 A resolution were obtained using
sodium formate as a precipitating agent. They belonged to space group P21, with
unit-cell parameters a = 106.07, b = 208.61, c = 147.09 A, beta = 90.43 degrees .
Eight RlArDHT molecules (two tetramers) in the asymmetric unit give a VM value of
3.2 A(3) Da(-1) and a solvent content of 62%. Crystals of CcXyDHT that diffracted
to 2.66 A resolution were obtained using sodium formate and polyethylene glycol
3350. They belonged to space group C2, with unit-cell parameters a = 270.42, b =
236.13, c = 65.17 A, beta = 97.38 degrees . Four CcXyDHT molecules (a tetramer)
in the asymmetric unit give a VM value of 4.0 A(3) Da(-1) and a solvent content
of 69%.
PMID- 27487925
TI - Structure of the lutein-binding domain of human StARD3 at 1.74 A resolution and
model of a complex with lutein.
AB - A crystal structure of the lutein-binding domain of human StARD3 (StAR-related
lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 A
resolution. A previous structure of the same protein determined to 2.2 A
resolution highlighted homology with StARD1 and shared cholesterol-binding
character. StARD3 has since been recognized as a carotenoid-binding protein in
the primate retina, where its biochemical function of binding lutein with
specificity appears to be well suited to recruit this photoprotective molecule.
The current and previous structures correspond closely to each other (r.m.s.d. of
0.25 A), especially in terms of the helix-grip fold constructed around a solvent
filled cavity. Regions of interest were defined with alternate conformations in
the current higher-resolution structure, including Arg351 found within the cavity
and Omega1, a loop of four residues found just outside the cavity entrance.
Models of the complex with lutein generated by rigid-body docking indicate that
one of the ionone rings must protrude outside the cavity, and this insight has
implications for molecular interactions with transport proteins and enzymes that
act on lutein. Interestingly, models with the E-ionone ring characteristic of
lutein pointing towards the bottom of the cavity were associated with fewer
steric clashes, suggesting that steric complementarity and ligand asymmetry may
play a role in discriminating lutein from the other ocular carotenoids zeaxanthin
and meso-zeaxanthin, which only have beta-ionone rings.
PMID- 27487926
TI - Structural analysis of a function-associated loop mutant of the substrate
recognition domain of Fbs1 ubiquitin ligase.
AB - The SCF ubiquitin ligase comprises four components: Skp1, Cul1, Rbx1 and a
variable-subunit F-box protein. The F-box protein Fbs1, which recognizes the N
linked glycoproteins, is involved in the endoplasmic reticulum-associated
degradation pathway. Although FBG3, another F-box protein, shares 51% sequence
identity with Fbs1, FBG3 does not bind glycoproteins. To investigate the sequence
structure relationship of the substrate-binding pocket, the crystal structure of
a mutant substrate-binding domain of Fbs1 in which the six nonconserved regions
(beta1, beta2-beta3, beta3-beta4, beta5-beta6, beta7-beta8 and beta9-beta10) of
Fbs1 were substituted with those of FBG3 was determined. The substrate-binding
pocket of this model exhibits structural features that differ from those of Fsb1.
PMID- 27487927
TI - Crystal structures of a subunit of the formylglycinamide ribonucleotide
amidotransferase, PurS, from Thermus thermophilus, Sulfolobus tokodaii and
Methanocaldococcus jannaschii.
AB - The crystal structures of a subunit of the formylglycinamide ribonucleotide
amidotransferase, PurS, from Thermus thermophilus, Sulfolobus tokodaii and
Methanocaldococcus jannaschii were determined and their structural
characteristics were analyzed. For PurS from T. thermophilus, two structures were
determined using two crystals that were grown in different conditions. The four
structures in the dimeric form were almost identical to one another despite their
relatively low sequence identities. This is also true for all PurS structures
determined to date. A few residues were conserved among PurSs and these are
located at the interaction site with PurL and PurQ, the other subunits of the
formylglycinamide ribonucleotide amidotransferase. Molecular-dynamics simulations
of the PurS dimer as well as a model of the complex of the PurS dimer, PurL and
PurQ suggest that PurS plays some role in the catalysis of the enzyme by its
bending motion.
PMID- 27487928
TI - Crystal structure of the antigen-binding fragment of a monoclonal antibody
specific for the multidrug-resistance-linked ABC transporter human P
glycoprotein.
AB - P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to
multidrug resistance in cancers that plays important roles in the
pharmacokinetics of a large number of drugs. The drug-resistance phenotype of P
gp can be modulated by the monoclonal antibody UIC2, which specifically
recognizes human P-gp in a conformation-dependent manner. Here, the purification,
sequence determination and high-resolution structure of the Fab fragment of UIC2
(UIC2/Fab) are reported. Purified UIC2/Fab binds human P-gp with a 1:1
stoichiometry. Crystals of UIC2/Fab are triclinic (space group P1), with unit
cell parameters a = 40.67, b = 44.91, c = 58.09 A, alpha = 97.62, beta = 99.10,
gamma = 94.09 degrees , and diffracted X-rays to 1.6 A resolution. The structure
was determined by molecular replacement and refined to 1.65 A resolution. The
asymmetric unit contains one molecule of UIC2/Fab, which exhibits a positively
charged antigen-binding surface, suggesting that it might recognize an oppositely
charged extracellular epitope of P-gp.
PMID- 27487929
TI - Crystal structure of Rv3899c(184-410), a hypothetical protein from Mycobacterium
tuberculosis.
AB - Rv3899c is a hypothetical protein from Mycobacterium tuberculosis which is
conserved across mycobacteria. It is predicted to be secreted and has been found
in culture filtrates. It has been proposed as a potential vaccine candidate;
however, its biological function is unknown. Here, the global structure of
Rv3899c(184-410), a fragment of Rv3899c, is reported. The structure resembles the
shell of a sea snail, and its N- and C-termini form two relatively independent
compact domains: an alpha/beta/alpha sandwich folding domain and an alpha-helix
bundle domain. There are no reported protein structures for any Rv3899c
homologues; this structure provides the first structural glimpse of a new protein
family consisting of Rv3899c and its homologues.
PMID- 27487930
TI - Characterization of the NTPR and BD1 interacting domains of the human PICH-BEND3
complex.
AB - Chromosome integrity depends on DNA structure-specific processing complexes that
resolve DNA entanglement between sister chromatids. If left unresolved, these
entanglements can generate either chromatin bridging or ultrafine DNA bridging in
the anaphase of mitosis. These bridge structures are defined by the presence of
the PICH protein, which interacts with the BEND3 protein in mitosis. To obtain
structural insights into PICH-BEND3 complex formation at the atomic level, their
respective NTPR and BD1 domains were cloned, overexpressed and crystallized using
1.56 M ammonium sulfate as a precipitant at pH 7.0. The protein complex readily
formed large hexagonal crystals belonging to space group P6122, with unit-cell
parameters a = b = 47.28, c = 431.58 A and with one heterodimer in the asymmetric
unit. A complete multiwavelength anomalous dispersion (MAD) data set extending to
2.2 A resolution was collected from a selenomethionine-labelled crystal at the
Swiss Light Source.
PMID- 27487932
TI - Cross-sectional imaging in cancers of the head and neck: how we review and
report.
AB - Cancer of the head and neck is the sixth most frequent cancer worldwide and
associated with significant morbidity. The head and neck area is complex and
divided into various anatomical and functional subunits. Imaging is performed by
cross-sectional modalities like computed tomography, magnetic resonance imaging,
ultrasound and positron emission tomography-computed tomography, usually with
fluorine-18-deoxy-D-glucose. Therefore, knowledge of the cross-sectional anatomy
is very important. This article seeks to give an overview of the various cross
sectional imaging modalities used in the evaluation of head and neck cancers. It
briefly describes the anatomy of the extracranial head and neck and the role of
imaging as well as the imaging appearance of tumours and their extension to lymph
nodes, bone and surrounding tissue. The advantages and disadvantages as well as
basic requirements of the various modalities are described along with ways of
optimizing imaging quality. A general guideline for prescription of the various
modalities is given. Pitfalls are many and varied and can be due to anatomical
variation, due to pathology which can be misinterpreted and technical due to
peculiarities of the various imaging modalities. Knowledge of these pitfalls can
help to avoid misinterpretation. The important points to be mentioned while
reporting are also enumerated.
PMID- 27487933
TI - Protein patterning by a DNA origami framework.
AB - A spatial arrangement of proteins provides structural and functional advantages
in vast technological applications as well as fundamental research. Most protein
patterning procedures employ complicated, time consuming and very costly
nanofabrication techniques. As an alternative route, we developed a fully
biomolecular self-assembly method using DNA Origami Frames (DOF) as a template
for both small and large scale protein patterning. We employed a triangular DOF
(tDOF) to arrange the Bovine Serum Albumin (BSA) protein. Our in situ protein
patterning strategy provides a novel, fully organic platform using a fast and low
cost surface approach with possible utilization in fundamental science and
technological applications.
PMID- 27487931
TI - Crystal structure of AibC, a reductase involved in alternative de novo isovaleryl
coenzyme A biosynthesis in Myxococcus xanthus.
AB - Isovaleryl coenzyme A (IV-CoA) performs a crucial role during development and
fruiting-body formation in myxobacteria, which is reflected in the existence of a
de novo biosynthetic pathway that is highly upregulated when leucine, the common
precursor of IV-CoA, is limited. The final step in de novo IV-CoA biosynthesis is
catalyzed by AibC, a medium-chain dehydrogenase/reductase. Here, the crystal
structure of AibC from Myxococcus xanthus refined to 2.55 A resolution is
presented. The protein adopts two different conformations in the crystal lattice,
which is a consequence of partial interaction with the purification tag. Based on
this structure, it is suggested that AibC most probably uses a Zn(2+)-supported
catalytic mechanism in which NADPH is preferred over NADH. Taken together, this
study reveals structural details of the alternative IV-CoA-producing pathway in
myxobacteria, which may serve as a base for further biotechnological research and
biofuel production.
PMID- 27487934
TI - Adenomyoepithelioma of the breast with late pulmonary metastases - case report
and review of the literature.
AB - BACKGROUND: Adenomyoepithelioma (AME) of the breast is a rare tumour of
unpredictable clinical behaviour. Most of the tumours are benign with some giving
local recurrences or distant metastases. CASE PRESENTATION: We report a case of
late lung metastases in a woman with a history of breast adenomyoepithelioma.
Partial lobectomy was performed for lung lesions and initial diagnosis was
epithelial-myoepithelial carcinoma. CONCLUSION: Careful slide's revision of both
breast and pulmonary lesions showed identical microscopic appearance with lung
tumour performing more malignant features. Tumour cells in both: breast and
pulmonary lesions were positive for cytokeratin and EMA (epithelial cells) and
also for SMA, S100 and vimentin (myoepithelial cells). Two years and 7 months
follow-up showed no recurrent neoplastic disease in our patient.
PMID- 27487936
TI - Peptide self-assembly: thermodynamics and kinetics.
AB - Self-assembling systems play a significant role in physiological functions and
have therefore attracted tremendous attention due to their great potential for
applications in energy, biomedicine and nanotechnology. Peptides, consisting of
amino acids, are among the most popular building blocks and programmable
molecular motifs. Nanostructures and materials assembled using peptides exhibit
important potential for green-life new technology and biomedical applications
mostly because of their bio-friendliness and reversibility. The formation of
these ordered nanostructures pertains to the synergistic effect of various
intermolecular non-covalent interactions, including hydrogen-bonding, pi-pi
stacking, electrostatic, hydrophobic, and van der Waals interactions. Therefore,
the self-assembly process is mainly driven by thermodynamics; however, kinetics
is also a critical factor in structural modulation and function integration. In
this review, we focus on the influence of thermodynamic and kinetic factors on
structural assembly and regulation based on different types of peptide building
blocks, including aromatic dipeptides, amphiphilic peptides, polypeptides, and
amyloid-relevant peptides.
PMID- 27487935
TI - Aroma characterization based on aromatic series analysis in table grapes.
AB - Aroma is an important part of quality in table grape, but the key aroma compounds
and the aroma series of table grapes remains unknown. In this paper, we
identified 67 aroma compounds in 20 table grape cultivars; 20 in pulp and 23 in
skin were active compounds. C6 compounds were the basic background volatiles, but
the aroma contents of pulp juice and skin depended mainly on the levels of esters
and terpenes, respectively. Most obviously, 'Kyoho' grapevine series showed high
contents of esters in pulp, while Muscat/floral cultivars showed abundant
monoterpenes in skin. For the aroma series, table grapes were characterized
mainly by herbaceous, floral, balsamic, sweet and fruity series. The simple and
visualizable aroma profiles were established using aroma fingerprints based on
the aromatic series. Hierarchical cluster analysis (HCA) and principal component
analysis (PCA) showed that the aroma profiles of pulp juice, skin and whole
berries could be classified into 5, 3, and 5 groups, respectively. Combined with
sensory evaluation, we could conclude that fatty and balsamic series were the
preferred aromatic series, and the contents of their contributors (beta-ionone
and octanal) may be useful as indicators for the improvement of breeding and
cultivation measures for table grapes.
PMID- 27487937
TI - Systemic lupus erythematosus: New role for CD95L in TH17 cell recruitment.
PMID- 27487938
TI - Osteoarthritis: Joint resurfacing possibilities loom large.
PMID- 27487940
TI - Hexagonal NiS nanobelts as advanced cathode materials for rechargeable Al-ion
batteries.
AB - Hexagonal NiS nanobelts served as novel cathode materials for rechargeable Al-ion
batteries based on an AlCl3/[EMIm]Cl ionic liquid electrolyte system. The nano
banded structure of the materials can facilitate the electrolyte immersion and
enhance Al(3+) diffusion. The hexagonal NiS nanobelt based cathodes exhibit high
storage capacity, good cyclability and low overpotential.
PMID- 27487939
TI - Ceramide mediates FasL-induced caspase 8 activation in colon carcinoma cells to
enhance FasL-induced cytotoxicity by tumor-specific cytotoxic T lymphocytes.
AB - FasL-mediated cytotoxicity is one of the mechanisms that CTLs use to kill tumor
cells. However, human colon carcinoma often deregulates the Fas signaling pathway
to evade host cancer immune surveillance. We aimed at testing the hypothesis that
novel ceramide analogs effectively modulate Fas function to sensitize colon
carcinoma cells to FasL-induced apoptosis. We used rational design and
synthesized twenty ceramide analogs as Fas function modulators. Five ceramide
analogs, IG4, IG7, IG14, IG17, and IG19, exhibit low toxicity and potent activity
in sensitization of human colon carcinoma cells to FasL-induced apoptosis.
Functional deficiency of Fas limits both FasL and ceramide analogs in the
induction of apoptosis. Ceramide enhances FasL-induced activation of the MAPK, NF
kappaB, and caspase 8 despite induction of potent tumor cell death. Finally, a
sublethal dose of several ceramide analogs significantly increased CTL-mediated
and FasL-induced apoptosis of colon carcinoma cells. We have therefore developed
five novel ceramide analogs that act at a sublethal dose to enhance the efficacy
of tumor-specific CTLs, and these ceramide analogs hold great promise for further
development as adjunct agents in CTL-based colon cancer immunotherapy.
PMID- 27487941
TI - Magnetic domain wall gratings for magnetization reversal tuning and confined
dynamic mode localization.
AB - High density magnetic domain wall gratings are imprinted in ferromagnetic
antiferromagnetic thin films by local ion irradiation by which alternating head
to-tail-to-head-to-tail and head-to-head-to-tail-to-tail spatially overlapping
domain wall networks are formed. Unique magnetic domain processes result from the
interaction of anchored domain walls. Non-linear magnetization response is
introduced by the laterally distributed magnetic anisotropy phases. The locally
varying magnetic charge distribution gives rise to localized and guided
magnetization spin-wave modes directly constrained by the narrow domain wall
cores. The exchange coupled multiphase material structure leads to unprecedented
static and locally modified dynamic magnetic material properties.
PMID- 27487942
TI - Rapid screening of copper intermediates in Cu(i)-catalyzed azide-alkyne
cycloaddition using a modified ICP-MS/MS platform.
AB - Rapid screening of Cu(+)-intermediates by using (63)Cu(+) or (65)Cu(+) ions as
catalysts with or without ligand protection in Cu(i)-catalyzed azide-alkyne
cycloaddition was realized using an on-line modified ICP-MS/MS platform in this
work, while the Cu(+)-intermediates without ligand protection are very active,
which are extremely difficult to be observed using other existing techniques.
This universal platform was suitable to study the mechanism of organic reactions
catalyzed by unstable metal(i) ions as well as to discover new candidates for
metal(i) catalysts.
PMID- 27487943
TI - Street-level bureaucracy and policy implementation in community public health
nursing: a qualitative study of the experiences of student and novice health
visitors.
AB - : Aim To explore the experiences of student and novice health visitors in
implementing health visiting policy reform pre- and post-qualification.
BACKGROUND: In England, public health nursing has been subject to major policy
reform. The Health Visitor Implementation Plan (2011) set out a plan to recruit
increasing numbers of nurses and midwives to the profession to deliver an
expanded and refocussed health visiting service. Exploring this policy change
from the viewpoint of those new to health visiting offers a unique perspective
into how a specific policy vision is translated into nursing practice. METHODS: A
descriptive qualitative study in which participants were enrolled on a one-year
post-graduate health visiting course at a University in South West of England.
Qualitative data were collected pre- and post-qualification. A total of 16
interviews and a focus group were conducted with nine participants between
September 2012 and March 2013. Findings Descriptive data were interpreted using
Lipsky's theoretical framework of street-level bureaucracy. Three themes emerged
which relate to this 'bottom-up' perspective on policy implementation; readiness
to operationalise policy, challenges in delivering the service vision; and using
discretion in delivering the vision. Community public health nurses operate as
street-level bureaucrats in negotiating the demands of policy and practice, and
by this means, attempt to reconcile professional values with institutional
constraints. Barriers to policy implementation at a local level mediate the
effects of policy reform, ultimately impacting upon outcomes for children and
families.
PMID- 27487944
TI - The long terminal repeat negative control region is a critical element for
insertional oncogenesis after gene transfer into hematopoietic progenitors with
Moloney murine leukemia viral vectors.
AB - Integrating vectors based on gamma-retroviruses and containing full-length long
terminal repeats (LTRs) have been associated with activation of oncogene
expression and leukemogenesis in human gene therapy trials. Identification of the
specific molecular elements of the LTRs that have a role in insertional
oncogenesis events is important as it can lead to the development of safer gene
transfer vectors. The negative control region (NCR) of the LTR is a particularly
well-conserved sequence among mammalian gamma-retroviruses with demonstrated
regulatory activity of gene transcription in hematopoietic cells, which led us to
hypothesize that this region may have a role in insertional oncogenesis after
gamma-retroviral vector (GV)-mediated gene transfer into hematopoietic
progenitors. We used an in vitro assay of murine bone marrow cell immortalization
to compare the immortalization capabilities of a series of GVs carrying murine
leukemia virus (MLV) LTR deletion mutants. Compared with GV carrying the full
length MLV LTR, deletion of the complete LTR enhancer sequence showed significant
reduction of immortalization rates. However, the use of a mutant LTR deleted of
the enhancer sequence, with exception of the NCR, did not affect immortalization.
Importantly, the inclusion of an LTR mutant devoid only of the NCR did show
significant reduction of immortalization rates compared with the full LTR
sequence. Therefore, our data point to the NCR as a key element for
immortalization and justify additional studies to evaluate its specific role in
MLV-mediated insertional oncogenesis.
PMID- 27487945
TI - Relationship between body mass index and family functioning, family
communication, family type and parenting style among African migrant parents and
children in Victoria, Australia: a parent-child dyad study.
AB - BACKGROUND: Although childhood obesity prevalence is stabilised in developed
countries including Australia, it is continuing to rise among migrants and
socially disadvantaged groups in these countries. African migrants and refugees
in particular, are at high risk of obesity due to changes in their family
dynamics. The aim of this study was to examine the difference between children
and parental perception of family functioning, family communication, family type
and parenting styles and their relationship with body mass index. METHODS: A
cross-sectional parent-child dyad study was conducted among 284 African families
from migrant and refugee backgrounds living in metropolitan Melbourne, Australia.
Bilingual workers were trained to collect demographic, anthropometric and
questionnaire data on family functioning, parenting, family type and family
communication. RESULTS: Parents and children reported different levels of family
dynamics. Children reported a higher prevalence of poor family functioning (61.5
%, 95 % CI: 55.6, 67.2 versus 56.8 %, 95 % CI: 49.7, 61.6) and protective family
type (29 %, 95 % CI: 23.9, 34.5 vs. 13.4 %, 95 % CI: 9.9, 17.9), but a lower
prevalence of authoritative parenting style (51.6 %, 95 % CI: 45.7, 57.5 vs. 63
%, 95 % CI: 57.5, 68.8) than parents. There was a positive relationship between
poor family functioning and child BMI both before (beta = 1.28; 95 % CI: 0.14,
2.41; p < 0.05) and after (beta = 1.73; 95 % CI: 0.53, 2.94; p < 0.001)
controlling for confounders, and an inverse relationship between consensual
family type and child BMI after adjustment (beta = -1.92; 95 % CI: -3.59, -0.24;
p < 0.05). There was no significant relationship between parental BMI and family
functioning, communication, family type or parenting style. CONCLUSION:
Children's perception of poor family functioning was associated with childhood
obesity. Family interventions to reduce childhood obesity need to adopt an
intergenerational approach to promote a clear understanding of family dynamics
between children and parents. Unless these intergenerational challenges
associated with family dynamics are clearly addressed in obesity interventions,
current obesity prevention initiatives will continue to widen the childhood
obesity gap in Australia.
PMID- 27487946
TI - Evolutionary and functional analysis of mulberry type III polyketide synthases.
AB - BACKGROUND: Type III polyketide synthases are important for the biosynthesis of
flavonoids and various plant polyphenols. Mulberry plants have abundant
polyphenols, but very little is known about the mulberry type III polyketide
synthase genes. An analysis of these genes may provide new targets for genetic
improvement to increase relevant secondary metabolites and enhance the plant
tolerance to biotic and abiotic stresses. RESULTS: Eighteen genes encoding type
III polyketide synthases were identified, including six chalcone synthases (CHS),
ten stilbene synthases (STS), and two polyketide synthases (PKS). Functional
characterization of four genes representing most of the MnCHS and MnSTS genes by
coexpression with 4-Coumaroyl-CoA ligase in Escherichia coli indicated that their
products were able to catalyze p-coumaroyl-CoA and malonyl-CoA to generate
naringenin and resveratrol, respectively. Microsynteny analysis within mulberry
indicated that segmental and tandem duplication events contributed to the
expansion of the MnCHS family, while tandem duplications were mainly responsible
for the generation of the MnSTS genes. Combining the evolution and expression
analysis results of the mulberry type III PKS genes indicated that MnCHS and
MnSTS genes evolved mainly under purifying selection to maintain their original
functions, but transcriptional subfunctionalization occurred during long-term
species evolution. Moreover, mulberry leaves can rapidly accumulated
oxyresveratrol after UV-C irradiation, suggesting that resveratrol was converted
to oxyresveratrol. CONCLUSIONS: Characterizing the functions and evolution of
mulberry type III PKS genes is crucial for advancing our understanding of these
genes and providing the basis for further studies on the biosynthesis of relevant
secondary metabolites in mulberry plants.
PMID- 27487947
TI - Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion
Progression After Coronary Intervention During Statin Therapy.
AB - AIM: Clinical trials suggest that residual risks remain for coronary artery
disease (CAD) during low-density lipoprotein cholesterol (LDL-C) lowering
therapy. We aimed to investigate the role of exogenous lipids in the prognosis of
CAD after percutaneous coronary intervention (PCI). METHODS: A total of 145
patients with CAD, who underwent elective PCI, and 82 non-CAD (control) patients
were enrolled in this study. CAD patients underwent follow-up coronary
angiography 6-9 months after PCI, and were classified into three groups: 1)
patients who showed in-stent restenosis (ISR) in the original stented segment, 2)
patients with other non-target coronary atherosclerotic lesions (de novo), and 3)
patients with neither ISR nor a de novo lesion. Biochemical analyses were
performed on fasting serum samples at the time of follow-up coronary angiography.
RESULTS: Despite the controlled serum LDL-C levels, CAD patients with statin
showed elevated cholesterol absorption marker campesterol/total cholesterol (TC),
synthesis marker lathosterol/TC, campesterol/lathosterol ratio, and
apolipoprotein B48 (apoB48) concentration compared with non-CAD patients. The
high campesterol/TC, campesterol/lathosterol ratio, and apoB48 concentration were
associated with de novo lesion progression after PCI. In stepwise multivariate
logistic regression analysis, campesterol/TC and apoB48 concentrations were
independent risk factors for de novo lesion progression in statin-treated CAD
patients after PCI. CONCLUSION: The increase of cholesterol absorption marker and
apoB48 concentration may lead to the progression of de novo lesions, and these
markers may represent a residual risk during statin treatment after PCI.
PMID- 27487948
TI - Comparative genomic analysis of retrogene repertoire in two green algae Volvox
carteri and Chlamydomonas reinhardtii.
AB - BACKGROUND: Retroposition, one of the processes of copying the genetic material,
is an important RNA-mediated mechanism leading to the emergence of new genes.
Because the transcription controlling segments are usually not copied to the new
location in this mechanism, the duplicated gene copies (retrocopies) become
pseudogenized. However, few can still survive, e.g. by recruiting novel
regulatory elements from the region of insertion. Subsequently, these duplicated
genes can contribute to the formation of lineage-specific traits and phenotypic
diversity. Despite the numerous studies of the functional retrocopies
(retrogenes) in animals and plants, very little is known about their presence in
green algae, including morphologically diverse species. The current availability
of the genomes of both uni- and multicellular algae provides a good opportunity
to conduct a genome-wide investigation in order to fill the knowledge gap in
retroposition phenomenon in this lineage. RESULTS: Here we present a comparative
genomic analysis of uni- and multicellular algae, Chlamydomonas reinhardtii and
Volvox carteri, respectively, to explore their retrogene complements. By adopting
a computational approach, we identified 141 retrogene candidates in total in both
genomes, with their fraction being significantly higher in the multicellular
Volvox. Majority of the retrogene candidates showed signatures of functional
constraints, thus indicating their functionality. Detailed analyses of the
identified retrogene candidates, their parental genes, and homologs of both,
revealed that most of the retrogene candidates were derived from ancient
retroposition events in the common ancestor of the two algae and that the
parental genes were subsequently lost from the respective lineages, making many
retrogenes 'orphan'. CONCLUSION: We revealed that the genomes of the green algae
have maintained many possibly functional retrogenes in spite of experiencing
various molecular evolutionary events during a long evolutionary time after the
retroposition events. Our first report about the retrogene set in the green algae
provides a good foundation for any future investigation of the repertoire of
retrogenes and facilitates the assessment of the evolutionary impact of
retroposition on diverse morphological traits in this lineage. REVIEWERS: This
article was reviewed by William Martin and Piotr Zielenkiewicz.
PMID- 27487949
TI - Primary intraspinal dumbbell-shaped mesenchymal chondrosarcoma with massive
calcifications: a case report and review of the literature.
AB - BACKGROUND: Mesenchymal chondrosarcoma is a rare malignant tumor arising from
bone or soft tissues. Instraspinal dumbbell-shaped mesenchymal chondrosarcoma is
even rarer; however, it should not be neglected by clinicians. CASE PRESENTATION:
A 26-year-old female was referred to our hospital with a 1.5-month history of
sciatic pain and numbness in the left leg. Computed tomography and magnetic
resonance imaging scans revealed an intraspinal dumbbell-shaped mass which had
distinguishing features of neurogenic tumors, surprisingly, with massive
calcifications, and no tumor metastasis was found. Then the patient underwent a
total resection of the tumor, and during the operation, we found that the right
nerve root of the fifth lumbar almost disappeared. The tumor was diagnosed as
mesenchymal chondrosarcoma by histopathological examination after operation.
Adjuvant therapies were not performed. However, recurrence of the tumor occurred
5 months later, and she underwent a total resection again combined with
radiotherapy after second surgery. CONCLUSIONS: To the best of our knowledge,
this case study presents the first report in literature about primary
instraspinal dumbbell-shaped mesenchymal chondrosarcoma with massive
calcifications, which may provide some evidence for clinical practice. As the
clinical symptoms and radiographic findings of mesenchymal chondrosarcoma are
usually not specific, clinicians should consider it as a possible case and
diagnose it through careful histopathological examination. Sometimes,
calcification could be seen in tumors, which may influence or reflect the growth
of tumor and disease prognosis. Although prognosis in mesenchymal chondrosarcoma
varies from person to person, generally, complete resection, adjuvant therapy,
and regular examinations are recommended to perform for patients with mesenchymal
chondrosarcoma.
PMID- 27487950
TI - Carrageenan delays cell cycle progression in human cancer cells in vitro
demonstrated by FUCCI imaging.
AB - BACKGROUND: Carrageenan is a sulfated polysaccharide that exists in red seaweeds
recently shown to have anticancer properties. Previous findings show various
effects of carrageenan suppressing tumor cell growth. One of the hallmarks of
cancer is uncontrolled proliferation, a consequence of loss of normal cell-cycle
control, that underlies tumor growth. Recently there is an increasing interest in
potential anticancer agents that affect cell cycle in cancer cells. Thus, in this
study we investigated the effects of carrageenan on the tumor cell cycle.
METHODS: Using human cervical carcinoma cells (HeLa) cells as and human umbilical
vein endothelial cells (HUVEC), the cytotoxic effects of kappa carrageenan (k-CO)
and lambda carrageenan (lambda-CO) at the concentrations of 250-2500 MUg/mL were
observed. Cell viability was determined using the MTT assay while cell death
rates were determined using staining with calcein-AM/propidium iodide. Cell-cycle
profile and progression were demonstrated with HeLa cells expressing FUCCI
(fluorescence ubiquitination-based cell-cycle indicator) probes (HeLa-FUCCI).
RESULTS: Carrageenan had no significant effect on HUVEC (normal cells). In
contrast both forms of carrageenan were cytotoxic towards HeLa cells (cancer
cells). Furthermore, according to cell-cycle analysis with FUCCI cells, the cell
cycle of HeLa cells was delayed in specific phases due to different carrageenan
treatments. CONCLUSION: Considering these results, it could be suggested that
carrageenan affects the cell-cycle of HeLa cells not only by arresting the cell
cycle in specific phases but also by delaying the time needed for the cell to
progress through the cell cycle. Additionally, different types of carrageenans
have different effects on cell cycle progression. This effect of carrageenan
towards cancer cells could possibly be developed into a tumor cell-specific
anticancer agent.
PMID- 27487951
TI - Benefits of Adding a Rapid PCR-Based Blood Culture Identification Panel to an
Established Antimicrobial Stewardship Program.
AB - Studies have demonstrated that the combination of antimicrobial stewardship
programs (ASP) and rapid organism identification improves outcomes in bloodstream
infections (BSI) but have not controlled for the incremental contribution of the
individual components. Hospitalized adult patients with blood culture pathogens
on a rapid, multiplex PCR-based blood culture identification panel (BCID) that
included 19 bacterial species, 5 Candida spp., and 4 antimicrobial resistance
genes were studied over sequential time periods in a pre-post quasiexperimental
study in 3 groups in the following categories: conventional organism
identification (controls), conventional organism identification with ASP (AS),
and BCID with ASP (BCID). Clinical and economic outcomes were compared between
groups. There were 783 patients with positive blood cultures; of those patients,
364 (115 control, 104 AS, and 145 BCID) met inclusion criteria. The time from
blood culture collection to organism identification was shorter in the BCID group
(17 h; P < 0.001) than in the control group (57 h) or the AS group (54 h). The
BCID group had a shorter time to effective therapy (5 h; P < 0.001) than the
control group (15 h) or AS group (13 h). The AS (57%) and BCID (52%) groups had
higher rates of antimicrobial de-escalation than the control group (34%), with de
escalation occurring sooner in the BCID group (48 h; P = 0.034) than in the AS
group (61 h) or the control group (63 h). No difference between the control
group, AS group, and BCID group was seen with respect to mortality, 30-day
readmission, intensive care unit length of stay (LOS), postculture LOS, or costs.
In patients with BSI, ASP alone improved antimicrobial utilization. Addition of
BCID to an established ASP shortened the time to effective therapy and further
improved antimicrobial use compared to ASP alone, even in a setting of low
antimicrobial resistance rates.
PMID- 27487952
TI - Norovirus Whole-Genome Sequencing by SureSelect Target Enrichment: a Robust and
Sensitive Method.
AB - Norovirus full-genome sequencing is challenging due to sequence heterogeneity
among genomes. Previous methods have relied on PCR amplification, which is
problematic due to primer design, and transcriptome sequencing (RNA-Seq), which
nonspecifically sequences all RNA, including host and bacterial RNA, in stool
specimens. Target enrichment uses a panel of custom-designed 120-mer RNA baits
that are complementary to all publicly available norovirus sequences, with
multiple baits targeting each position of the genome, which overcomes the
challenge of primer design. Norovirus genomes are enriched from stool RNA
extracts to minimize the sequencing of nontarget RNA. SureSelect target
enrichment and Illumina sequencing were used to sequence full genomes from 507
norovirus-positive stool samples with reverse transcription-real-time PCR cycle
threshold (CT) values of 10 to 43. Sequencing on an Illumina MiSeq system in
batches of 48 generated, on average, 81% on-target reads per sample and 100%
genome coverage with >12,000-fold read depth. Samples included genotypes GI.1,
GI.2, GI.3, GI.6, GI.7, GII.1, GII.2, GII.3, GII.4, GII.5, GII.6, GII.7, GII.13,
GII.14, and GII.17. When outliers were accounted for, we generated >80% genome
coverage for all positive samples, regardless of CT values. A total of 164
samples were tested in parallel with conventional PCR genotyping of the capsid
shell domain; 164/164 samples were successfully sequenced, compared to 158/164
samples that were amplified by PCR. Four of the samples that failed capsid PCR
analysis had low titers, which suggests that target enrichment is more sensitive
than gel-based PCR. Two samples failed PCR due to primer mismatches; target
enrichment uses multiple baits targeting each position, thus accommodating
sequence heterogeneity among norovirus genomes.
PMID- 27487953
TI - Molecular Microbiological Profile of Chronic Suppurative Otitis Media.
AB - Chronic suppurative otitis media (CSOM) presents with purulent otorrhea (ear
discharge), is characterized by chronic inflammation of the middle ear and
mastoid cavity, and contributes to a significant disease burden worldwide.
Current antibiotic therapy is guided by swab culture results. In the absence of
detailed molecular microbiology studies of CSOM patients, our current
understanding of the microbiota of CSOM (and indeed of the healthy ear) remains
incomplete. In this prospective study, 24 patients with CSOM were recruited,
along with 22 healthy controls. Culture-based techniques and 16S rRNA gene
amplicon sequencing were used to profile the bacterial community for each
patient. Comparisons between patients with and without cholesteatoma in the
middle ear and mastoid cavity were also made. A major finding was that the middle
ear of many healthy controls was not sterile, which is contradictory to the
results of previous studies. However, sequencing data showed that Staphylococcus
aureus, along with a range of other Gram-positive and Gram-negative organisms,
were present in all subgroups of CSOM and healthy controls. Large interpatient
variability in the microbiota was observed within each subgroup of CSOM and
controls, and there was no bacterial community "signature" which was
characteristic of either health or disease. Comparisons of the culture results
with the molecular data show that culture-based techniques underestimate the
diversity of bacteria found within the ear. This study reports the first detailed
examination of bacterial profiles of the ear in healthy controls and patients
with CSOM.
PMID- 27487954
TI - Molecular Diagnostic Testing for Aspergillus.
AB - The direct detection of Aspergillus nucleic acid in clinical specimens has the
potential to improve the diagnosis of aspergillosis by offering more rapid and
sensitive identification of invasive infections than is possible with traditional
techniques, such as culture or histopathology. Molecular tests for Aspergillus
have been limited historically by lack of standardization and variable
sensitivities and specificities. Recent efforts have been directed at addressing
these limitations and optimizing assay performance using a variety of specimen
types. This review provides a summary of standardization efforts and outlines the
complexities of molecular testing for Aspergillus in clinical mycology.
PMID- 27487955
TI - Spatiotemporal Expression Patterns and Antibody Reactivity of Taeniidae
Endophilin B1.
AB - Larval Taeniidae, such as metacestodes of Taenia solium, Echinococcus granulosus,
and Echinococcus multilocularis, produce chronic and fatal helminthic diseases.
Proper identification of these zoonotic cestodiases is often challenging and is
hampered in some clinical settings. Endophilin B1 plays critical roles in the
maintenance of membrane contours and endocytosis. We isolated proteins homologous
to endophilin B1 from T. solium, Taenia saginata, and Taenia asiatica The three
Taeniidae endophilin B1 proteins shared 92.9 to 96.6% sequence identity. They
harbored a Bin1/amphiphysin/Rvs (BAR) domain and residues for a dimeric interface
but lacked a SRC homology 3 (SH3) domain. Endophilin B1 showed a unique
immunological profile and was abundantly expressed in the tegumental syncytium of
Taeniidae metacestodes and adults. Bacterially expressed recombinant T. solium
endophilin B1 (rTsMEndoB1) demonstrated a sensitivity of 79.7% (345/433 cases)
for serodiagnosis of larval Taeniidae infections. The protein showed strong
immune recognition patterns against sera from patients with chronic
neurocysticercosis, cystic echinococcosis, or advanced-stage alveolar
echinococcosis. Adult Taeniidae infections exhibited moderate degrees of positive
antibody responses (65.7% [23/35 samples]). rTsMEndoB1 showed some cross
reactivity with sera from patients infected with Diphyllobothriidae (23.6%
[25/106 samples]) but not with sera from patients with other parasitic diseases
or normal controls. The specificity was 91.7% (256/301 samples). The positive and
negative predictive values were 93.6% and 73.4%, respectively. Our results
demonstrate that Taeniidae endophilin B1 may be involved in the control of
membrane dynamics, thus contributing to shaping and maintaining the tegumental
curvature. rTsMEndoB1 may be useful for large-scale screening, as well as for
individual diagnosis and follow-up surveillance of Taeniidae infections.
PMID- 27487956
TI - Evaluation of Semiautomated IS6110-Based Restriction Fragment Length Polymorphism
Typing for Mycobacterium tuberculosis in a High-Burden Setting.
AB - The manual IS6110-based restriction fragment length polymorphism (RFLP) typing
method is highly discriminatory; however, it is laborious and technically
demanding, and data exchange remains a challenge. In an effort to improve IS6110
based RFLP to make it a faster format, DuPont Molecular Diagnostics recently
introduced the IS6110-PvuII kit for semiautomated typing of Mycobacterium
tuberculosis using the RiboPrinter microbial characterization system. This study
aimed to evaluate the semiautomated RFLP typing against the standard manual
method. A total of 112 isolates collected between 2013 and 2014 were included.
All isolates were genotyped using manual and semiautomated RFLP typing methods.
Clustering rates and discriminatory indexes were compared between methods. The
overall performance of semiautomated RFLP compared to manual typing was
excellent, with high discriminatory index (0.990 versus 0.995, respectively) and
similar numbers of unique profiles (72 versus 74, respectively), numbers of
clustered isolates (33 versus 31, respectively), cluster sizes (2 to 6 and 2 to 5
isolates, respectively), and clustering rates (21.9% and 17.1%, respectively).
The semiautomated RFLP system is technically simple and significantly faster than
the manual RFLP method (8 h versus 5 days). The analysis is fully automated and
generates easily manageable databases of standardized fingerprints that can be
easily exchanged between laboratories. Based on its high-throughput processing
with minimal human effort, the semiautomated RFLP can be a very useful tool as a
first-line method for routine typing of M. tuberculosis isolates, especially
where Beijing strains are highly prevalent, followed by manual RFLP typing if
resolution is not achieved, thereby saving time and labor.
PMID- 27487957
TI - Characterization of Vibrio cholerae Strains Isolated from the Nigerian Cholera
Outbreak in 2010.
AB - We examined clinical samples from Nigerian patients with acute watery diarrhea
for Vibrio cholerae during the 2010 cholera outbreak. A total of 109 suspected
isolates were characterized, but only 57 V. cholerae strains could be confirmed
using multiplex real-time PCR as well as rpoB sequencing and typed as V. cholerae
O:1 Ogawa biotype El Tor. This finding highlighted the need for accurate
diagnosis of cholera in epidemic countries to implement life-saving
interventions.
PMID- 27487958
TI - A Novel SimpleProbe PCR Assay for Detection of Mutations in the 23S rRNA Gene
Associated with Macrolide Resistance in Mycoplasma genitalium in Clinical
Samples.
AB - Macrolide-resistant strains of Mycoplasma genitalium are an increasing problem
throughout the world, and the implementation of a rapid and sensitive assay for
mutation detection to guide treatment is needed. Macrolide-resistant strains have
been shown to contain base substitutions in positions 2058 and 2059 (Escherichia
coli numbering) in region V of the 23S rRNA gene. In this study, we present a
SimpleProbe PCR followed by melting curve analysis to differentiate between
macrolide-resistant mutants and wild types. The assay was performed on 159
Mycoplasma genitalium-positive samples, and the results were compared with DNA
sequencing. We also looked at the prevalence of macrolide-resistant strains in a
Norwegian population. Of 139 samples characterized successfully by sequencing, 54
(39%) were wild types and 85 (61%) were mutants, consisting of 59 (42%) A2059G,
24 (17%) A2058G, 1 (1%) A2058T, and 1 (1%) A2059C mutation. The melting curve
analysis correctly differentiated between wild-type and mutant strains in all
cases, but it could not identify the different mutant types. The SimpleProbe PCR
proved to be a simple, rapid, and reliable method for the detection of macrolide
resistant isolates of Mycoplasma genitalium in a clinical setting.
PMID- 27487959
TI - Proton pump inhibitors are associated with increased risk of development of
chronic kidney disease.
AB - BACKGROUND: Acute interstitial nephritis secondary to proton pump inhibitors
(PPIs) frequently goes undiagnosed due to its subacute clinical presentation,
which may later present as chronic kidney disease (CKD). We investigated the
association of PPI use with the development of CKD and death. METHODS: Two
separate retrospective case-control study designs were employed with a
prospective logistic regression analysis of data to evaluate the association of
development of CKD and death with PPI use. The population included 99,269
patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008.
For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first
observation in Veterans Affairs Health Care Upstate New York (VISN2) network data
system were excluded. Data obtained included use of PPI (Yes/No), demographics,
laboratory data, pre-PPI comorbidity variables. RESULTS: A total of 19,311/76,462
patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients
receiving PPI were less likely to have vascular disease, COPD, cancer and
diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758
died. A prospective logistic analysis of case-control data showed higher odds for
development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI
1.67-1.84) among patients taking PPIs versus those not on PPIs. CONCLUSIONS: Use
of proton pump inhibitors is associated with increased risk of development of CKD
and death. With the large number of patients being treated with proton pump
inhibitors, healthcare providers need to be better educated about the potential
side effects of these medications.
PMID- 27487960
TI - Readability of patient education materials in ophthalmology: a single-institution
study and systematic review.
AB - BACKGROUND: Patient education materials should be written at a level that is
understandable for patients with low health literacy. The aims of this study are
(1) to review the literature on readability of ophthalmic patient education
materials and (2) to evaluate and revise our institution's patient education
materials about glaucoma using evidence-based guidelines on writing for patients
with low health literacy. METHODS: A systematic search was conducted on the
PubMed/MEDLINE database for studies that have evaluated readability level of
ophthalmic patient education materials, and the reported readability scores were
assessed. Additionally, we collected evidence-based guidelines for writing easy
to-read patient education materials, and these recommendations were applied to
revise 12 patient education handouts on various glaucoma topics at our
institution. Readability measures, including Flesch-Kincaid Grade Level (FKGL),
and word count were calculated for the original and revised documents. The
original and revised versions of the handouts were then scored in random order by
two glaucoma specialists using the Suitability Assessment of Materials (SAM)
instrument, a grading scale used to evaluate suitability of health information
materials for patients. Paired t test was used to analyze changes in readability
measures, word count, and SAM score between original and revised handouts.
Finally, five glaucoma patients were interviewed to discuss the revised
materials, and patient feedback was analyzed qualitatively. RESULTS: Our
literature search included 13 studies that evaluated a total of 950 educational
materials. Among the mean FKGL readability scores reported in these studies, the
median was 11 (representing an eleventh-grade reading level). At our institution,
handouts' readability averaged a tenth-grade reading level (FKGL = 10.0 +/- 1.6),
but revising the handouts improved their readability to a sixth-grade reading
level (FKGL = 6.4 +/- 1.2) (p < 0.001). Additionally, the mean SAM score of our
institution's handouts improved from 60 +/- 7 % (adequate) for the original
versions to 88 +/- 4 % (superior) for the revised handouts (p < 0.001).
CONCLUSIONS: Our systematic review of the literature reveals that ophthalmic
patient education materials are consistently written at a level that is too high
for many patients to understand. Our institution's experience suggests that
applying guidelines on writing easy-to-understand material can improve the
readability and suitability of educational materials for patients with low health
literacy.
PMID- 27487962
TI - Commentary: Chloride Regulation: A Dynamic Equilibrium Crucial for Synaptic
Inhibition.
PMID- 27487961
TI - Impact of reticulated platelets on antiplatelet response to thienopyridines is
independent of platelet turnover.
AB - Reticulated platelets are associated with impaired antiplatelet response to
thienopyridines. It is uncertain whether this interaction is caused by a
decreased drug exposure due to high platelet turnover reflected by elevated
levels of reticulated platelets or by intrinsic properties of reticulated
platelets. This study sought to investigate if the impact of reticulated
platelets on early antiplatelet response to thienopyridines is mainly caused by
platelet turnover as previously suggested. Elective patients undergoing coronary
intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60
mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was
determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and
at day 1 after loading. Immature platelet count was assessed as marker of
reticulated platelets by flow cytometry. Platelet reactivity increased with
rising levels of immature platelet count in both groups. This effect was more
distinctive in patients on clopidogrel as compared to patients on prasugrel.
Overall, immature platelet count correlated well with on-treatment platelet
reactivity at all time-points (p < 0.001). These correlations did not change over
time in the entire cohort as well as in patients treated with clopidogrel or
prasugrel indicating an effect independent of platelet turnover (comparison of
correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of
immature platelet count with impaired antiplatelet response to thienopyridines is
similar early and late after loading. This finding suggests as main underlying
mechanism another effect of reticulated platelets on thienopyridines than
platelet turnover.
PMID- 27487963
TI - Could peptide-decorated nanoparticles provide an improved approach for treating
pregnancy complications?
PMID- 27487964
TI - Molecular Dynamics Simulations of Hydration Effects on Solvation, Diffusivity,
and Permeability in Chitosan/Chitin Films.
AB - The effects of hydration on the solvation, diffusivity, solubility, and
permeability of oxygen molecules in sustainable, biodegradable chitosan/chitin
food packaging films were studied via molecular dynamics and confined random walk
simulations. With increasing hydration, the membrane has a more homogeneous water
distribution with the polymer chains being fully solvated. The diffusivity
increased by a factor of 4 for oxygen molecules and by an order of magnitude for
water with increasing the humidity. To calculate the Henry's constant and
solubility of oxygen in the membranes with changing hydration, the excess
chemical potential was calculated via free energy perturbation, thermodynamic
integration and direct particle deletion methods. The simulations predicted a
higher solubility and permeability for the lower humidity, in contradiction to
experimental results. All three methods for calculating the solubility were in
good agreement. It was found that the Coulombic interactions in the potential
caused the oxygen to bind too strongly to the protonated amine group. Insight
from this work will help guide molecular modeling of chitosan/chitin membranes,
specifically permeability measurements for small solute molecules. Efforts to
chemically tailor chitosan/chitin membranes to favor discrete as opposed to
continuous aqueous domains could reduce oxygen permeability.
PMID- 27487965
TI - NKG2D Acts as a Co-Receptor for Natural Killer Cell-Mediated Anti-HIV-1 Antibody
Dependent Cellular Cytotoxicity.
AB - The utility of antibody-dependent cellular cytotoxicity (ADCC) for eliminating
HIV-1-infected cells is of much interest for the design of both prophylactic
vaccines for HIV-1 prevention and therapeutics to eliminate latently infected
cells following reactivation. Significant research has been conducted to
understand the antibody specificities involved in anti-HIV-1 ADCC responses.
Perhaps equally important as the identity of the antibodies mediating these
responses are factors regulating the ability of ADCC effector cells, in
particular, natural killer (NK) cells, to respond to antibody-coated target
cells. Indeed, a plethora of activating and inhibitory receptors expressed on the
surface of NK cells might act in conjunction with CD16 to influence ADCC. As the
expression of NKG2D and its ligands has been linked to HIV-1 disease progression,
we evaluated if signals through NKG2D were involved in anti-HIV-1 ADCC. Utilizing
assays measuring cytolysis, we provide the first data implicating NKG2D in
antibody-dependent NK cell responses against a target cell line either pulsed
with gp120 or infected with HIV-1. These observations are highly significant for
understanding antibody-dependent NK cell responses against HIV-1 and might be
useful for optimizing prophylactics and therapeutics aiming to utilize antibodies
and optimally functional NK cells to control HIV-1.
PMID- 27487966
TI - Community nurse-led initiation of antiviral therapy for chronic hepatitis C in
people who inject drugs does not increase uptake of or adherence to treatment.
AB - BACKGROUND: Chronic hepatitis C is common in people who inject drugs (PWID) and
this population serves as a reservoir for infection. Treatment levels are low
among this group, ranging from 1 to 19%. We explored whether a nurse-initiated
community treatment model increased uptake of and adherence to interferon-based
therapies. METHODS: This was a cluster randomized trial of nurse-initiated versus
physician-initiated antiviral therapy with pegylated interferon and ribavirin for
hepatitis C virus in community clinics (trial registration: ISRCTN07774040).
RESULTS: The proportion of participants initiating treatment during follow-up was
10% with nurse-initiated (6/62) and 9% with physician-initiated (6/76) therapy.
Adherence was similar in both groups, with only one patient in each arm not
adhering to therapy. There were no serious adverse events, but interferon-related
side effects were common. Drug and alcohol use did not change during therapy.
CONCLUSION: Despite easy access to antiviral therapy, uptake of treatment was
poor, with no significant difference between the groups. Nurse-led initiation of
interferon-based antiviral therapy in PWID did not lead to increased uptake of,
response to or adherence with treatment. Further service improvement is unlikely
to increase the proportion of PWID undergoing antiviral therapy for hepatitis C
virus and early adoption of interferon-free regimens may increase the proportion
initiating and completing treatment.
PMID- 27487967
TI - Factors Affecting Burn Contracture Outcome in Developing Countries: A Review of
2506 Patients.
AB - INTRODUCTION: Burn contractures hinder joint mobility, resulting in functional
impairment and reduced quality of life. This is of greater significance in
developing countries where there are fewer resources for assistance with such
impairments. Contracture release reduces deformity, but multiple factors affect
the extent of postsurgical improvements and outcomes. Elucidating these factors
may enable surgeons to better care for burn patients. This study assesses factors
that impact burn contracture resolution in developing nations. METHODS: A
retrospective review of 2506 burn contractures was performed using information
extracted from a large nongovernment organization (ReSurge International)
database from Nepal, India, and Zambia. Data points included age, type of burn,
time elapsed between injury and release, and extent of final release achieved
based on preoperative and postoperative images of hand (n = 1960), elbow (n =
371), and knee (n = 176) contractures. Hand improvement was scored based on
digit/wrist involvement (severity of dysfunction) and joint extension capability
(functionality); elbow and knee improvement were calculated using preoperative
and postoperative joint angles. Multivariate analysis was performed. RESULTS:
Hands burned by hot liquid had greater functionality after surgery than open-fire
burns (P < 0.01). Improvement in severity of dysfunction and functionality were
inversely correlated to age (P < 0.01) and time until surgery (P < 0.01). Elbow
improvement decreased as age increased (P < 0.01). Postoperative increase of knee
extension decreased for each year elapsed between injury and surgery (P < 0.01).
CONCLUSIONS: Burn type, age when burned, and timing of surgery were significant
factors affecting hand outcomes, whereas age affected elbow outcomes, and time
elapsed until surgery affected knee results. An algorithm was formulated to
enable physicians in developing countries with limited resources to triage
patients and optimize patient outcomes.
PMID- 27487968
TI - The Simultaneous Use of Breast Reduction and Internal Mammary Artery Perforator
Flap in Sternal Wound Reconstruction.
AB - Internal mammary artery perforator (IMAP)-based fasciocutaneous flaps have
recently gained popularity in sternal wound reconstruction due to their decreased
donor site morbidity. However, patients with significant macromastia or who are
obese present a challenge when using these flaps due to their anatomy and
associated comorbid conditions. Despite the prevalence of this population, there
is a relative paucity of data on the use of local fasciocutaneous flaps and
techniques to close sternotomy wounds in the obese population with hypertrophic
or ptotic breasts. The authors describe a novel technique using simultaneous
unilateral breast reduction with a fifth intercostal IMAP-based flap for closure
of a median sternotomy wound through a case presentation, an anatomical injection
study, and review of the literature. Five fresh female cadavers were used to
conduct 8 trials of injection of the IMAP arteries, isolation of the fifth IMAP
branch, and elevation of a local flap. The literature was comprehensively
reviewed with a total of 33 cases of IMAP flaps for sternal reconstruction being
described. The most commonly used perforators with the second and sixth IMAPs.
Overall complication rate was reported to be 9.1% (3/33), with 2 cases reporting
dehiscence and 1 with flap tip necrosis. No cases reported use of the fifth IMAP
or formal breast reduction procedures, which was successfully performed in a 40
year-old diabetic female patient history of multiple left-sided thoracic
surgeries and radiation with a chronic sternal wound.
PMID- 27487969
TI - Dilated right internal thoracic artery as a systemic pulmonary shunt.
AB - We report the use of a dilated right internal thoracic artery as a systemic
pulmonary shunt in a patient with a single ventricle who developed a systemic
pulmonary shunt stenosis following a modified Norwood's procedure. The systemic
to-pulmonary artery shunt was performed at 13 months of age, and the patient has
stable oxygen saturations five years after the surgery.
PMID- 27487970
TI - Corrigendum: Generation of stem cell-derived beta-cells from patients with type 1
diabetes.
PMID- 27487971
TI - Early dumping syndrome is not a complication but a desirable feature of Roux-en-Y
gastric bypass surgery.
AB - Early dumping syndrome after gastric bypass surgery due to rapid delivery of
hyperosmolar nutrients into the bowel causing intense symptoms is often described
as a complication. Twelve patients, mean age 47 years, were interviewed
approximately 9 years post-operation. The interviews were audiotaped and
transcribed verbatim, followed by an inductive content analysis to reveal
patients' experience of the dumping syndrome. The core category 'Dumping syndrome
is a positive consequence of Roux-en-Y gastric bypass surgery and a tool to
control food intake' was identified based on the following four sub-categories:
(i) 'The multidimensional emergence and effects of dumping syndrome', (ii)
'Dumping syndrome as something positive although unpleasant', (iii) 'Developing
coping mechanisms and ingenious strategies' and (iv) 'My own fault if I expose
myself to dumping syndrome'. From the patients' perspective, dumping syndrome
gives control over food intake; although the symptoms were unpleasant, patients
considered dumping syndrome as a positive protection against over-consumption.
Hence, healthcare professionals should not present dumping syndrome as a
complication but rather as an aid to control eating behaviour and excessive food
intake.
PMID- 27487972
TI - Organisational strategies to implement hospital pressure ulcer prevention
programmes: findings from a national survey.
AB - AIM: To describe the presence and operationalisation of organisational strategies
to support implementation of pressure ulcer prevention programmes across acute
care hospitals in a large, integrated health-care system. BACKGROUND:
Comprehensive pressure ulcer programmes include nursing interventions such as use
of a risk assessment tool and organisational strategies such as policies and
performance monitoring to embed these interventions into routine care. The
current literature provides little detail about strategies used to implement
pressure ulcer prevention programmes. METHODS: Data were collected by an e-mail
survey to all chief nursing officers in Veterans Health Administration acute care
hospitals. Descriptive and bivariate statistics were used to summarise survey
responses and evaluate relationships between some variables. RESULTS:
Organisational strategies that support implementation of a pressure ulcer
prevention programme (policy, committee, staff education, wound care specialists,
and use of performance data) were reported at high levels. Considerable
variations were noted in how these strategies were operationalised within
individual hospitals. CONCLUSION: Organisational strategies to support
implementation of pressure ulcer preventive programmes are often not optimally
operationalised to achieve consistent, sustainable performance. IMPLICATIONS FOR
NURSING MANAGEMENT: The results of the present study highlight the role and
influence of nurse leaders on pressure ulcer prevention program implementation.
PMID- 27487973
TI - Self-management in temporomandibular disorders: a systematic review of
behavioural components.
AB - The aim of this qualitative systematic review was to identify the behaviour
change techniques most frequently employed in published temporomandibular
disorder (TMD) self-management (SM) programmes. The reviewers matched the
components of SM programmes into the relevant behaviour change technique domains
according to the definitions of the behaviour change taxonomy (version 1).
Electronic databases were searched for randomised controlled trials assessing an
SM programme for TMD. Manual searches were also conducted for potentially
important journals. Eligibility criteria for the review included: the type of
study, the participants, the intervention utilised and the comparators/control.
Fifteen randomised controlled trials with 554 patients were included in this
review. The review concludes a minority of the available behaviour change
techniques are currently employed in SM programmes. Other behaviour change
techniques should be examined to see whether there is a theoretical underpinning
that might support their inclusion in self-management programmes in TMD. Further
trials are required to conclude that SM programmes are more effective than no
treatment at all and or placebo. With more structured SM programmes, greater
therapeutic benefits might be achieved, and certainly if SM programmes published
in the literature define their components through use of the behaviour change
taxonomy, it would be easier for clinicians to replicate efficacious programmes.
PMID- 27487974
TI - Pediatric Obesity: Is There Room for Active Video Games in Prevention or
Management?
AB - Children and adolescents spend a considerable amount of time engaged in sedentary
behaviors that have been shown to favor weight gain and impaired physical
fitness. Active video games have been proposed to increase physical activity
levels. Although active video games may offer an interesting alternative to
reducing sedentary time for children, the present commentary aimed to determine
whether there is adequate evidence that compared active video gaming to real-life
play and exercise. Given the dearth of data, it is not possible at present to
support the use of active video games as substitutes for traditional forms of
active play and health-enhancing physical activity. Further research should be
encouraged and therapists should not consider active video games exclusively for
intervention in children with obesity.
PMID- 27487975
TI - Comparative study of the effects of bupropion and escitalopram on Internet gaming
disorder.
AB - AIM: We compared the efficacy of bupropion and escitalopram treatments in
Internet gaming disorder (IGD) patients. METHODS: We recruited 119 adolescents
and adults with IGD. We treated these participants for 6 weeks in three groups as
follows: 44 participants were treated with bupropion SR (bupropion group), 42
participants were treated with escitalopram (escitalopram group), and 33 patients
without any medication were observed in the community (observation group). At
baseline and at the 6-week follow-up visit, all subjects were evaluated using the
Clinical Global Impression-Severity Scale, the Young Internet Addiction Scale,
the Beck Depression Inventory, the ADHD Rating Scale, and the Behavioral
Inhibition and Activation Scales. RESULTS: Both the escitalopram group and the
bupropion group showed improvement on all clinical symptom scales after 6 weeks
of treatment compared to the observation group. Additionally, the bupropion group
showed greater improvement on scores for the Clinical Global Impression-Severity
Scale, the Young Internet Addiction Scale, the ADHD Rating Scale, and the
Behavioral Inhibition Scale than the escitalopram group. CONCLUSION: Both
bupropion and escitalopram were effective in treating and managing IGD symptoms.
Moreover, bupropion appeared to be more effective than escitalopram in improving
attention and impulsivity in IGD patients. In addition, attention and impulsivity
seem to be important for the management of IGD.
PMID- 27487976
TI - The moderating role of intrinsic value in the relation between psychological
needs support and academic engagement in mathematics among Chinese adolescent
students.
AB - This study was to assess the moderating roles of intrinsic value in the relation
of basic psychological needs support to academic engagement in mathematics. We
recruited 246 middle school students by using the Basic Psychological Needs
Support Scale, the Intrinsic Value Scale and the Academic Engagement Scale. This
study found that both basic psychological needs support and intrinsic value had
significant predictions on the three aspects of academic engagement. Moreover,
the interaction item between basic psychological needs support and intrinsic
value could significantly affect emotional and cognitive engagement, but not
behavioural engagement. The findings indicated that except for behavioural
engagement, the associations between basic psychological need support and
emotional or cognitive engagement could be moderated by intrinsic value. This
study provides a special perspective for educators and researchers to recognise
the role of intrinsic value in promoting adolescents' higher levels of
involvement in mathematics class.
PMID- 27487977
TI - Growth and wetting of water droplet condensed between micron-sized particles and
substrate.
AB - We study heterogeneous condensation growth of water droplets on micron-sized
particles resting on a level substrate. Through numerical simulations on
equilibrium droplet profiles, we find multiple wetting states towards complete
wetting of the particle. Specifically, a partially wetting droplet could undergo
a spontaneous transition to complete wetting during condensation growth, for
contact angles above a threshold minimum. In addition, we find a competitive
wetting behavior between the particle and the substrate, and interestingly, a
reversal of the wetting dependence on contact angles during late stages of
droplet growth. Using quasi-steady assumption, we simulate a growing droplet
under a constant condensation flux, and the results are in good agreement with
our experimental observations. As a geometric approximation for particle
clusters, we propose and validate a pancake model, and with it, show that a
particle cluster has greater wetting tendency compared to a single particle.
Together, our results indicate a strong interplay between contact angle,
capillarity and geometry during condensation growth.
PMID- 27487978
TI - Inkjet Printing Based Mono-layered Photonic Crystal Patterning for Anti
counterfeiting Structural Colors.
AB - Photonic crystal structures can be created to manipulate electromagnetic waves so
that many studies have focused on designing photonic band-gaps for various
applications including sensors, LEDs, lasers, and optical fibers. Here, we show
that mono-layered, self-assembled photonic crystals (SAPCs) fabricated by using
an inkjet printer exhibit extremely weak structural colors and multiple colorful
holograms so that they can be utilized in anti-counterfeit measures. We
demonstrate that SAPC patterns on a white background are covert under daylight,
such that pattern detection can be avoided, but they become overt in a simple
manner under strong illumination with smartphone flash light and/or on a black
background, showing remarkable potential for anti-counterfeit techniques.
Besides, we demonstrate that SAPCs yield different RGB histograms that depend on
viewing angles and pattern densities, thus enhancing their cryptographic
capabilities. Hence, the structural colorations designed by inkjet printers would
not only produce optical holograms for the simple authentication of many items
and products but also enable a high-secure anti-counterfeit technique.
PMID- 27487979
TI - Short-term and long-term outcomes of laparoscopic hepatectomy, microwave
ablation, and open hepatectomy for small hepatocellular carcinoma: a 5-year
experience in a single center.
AB - AIM: Laparoscopic hepatectomy (LH), microwave ablation (MWA), and open
hepatectomy (OH) are three widely used methods to treat small hepatocellular
carcinoma (HCC). However, few studies have compared the short- and long-term
outcomes of these three treatments. The aim of this study was to investigate
their effectiveness. METHODS: The data were reviewed from 280 patients with HCCs
measuring <=3 cm (Barcelona Clinic Liver Cancer stage 0 or A) who received LH (n
= 133), OH (n = 87), or MWA (n = 60) in our research center from 2005 to 2010.
Short-term outcomes included intraoperative blood loss, operation time, and
length of hospital stay. The disease-free survival and overall survival rates
were analyzed as long-term outcomes. RESULTS: The patients in the MWA and LH
groups showed better short-term outcomes compared with those in the OH group.
There were no significant differences in overall survival rates among the three
treatments. The LH group showed significantly lower recurrence rates than the MWA
group (P = 0.0146). CONCLUSIONS: Laparoscopic hepatectomy may be a better option
for patients with small HCC located on the liver surface and left lateral lobe.
The short-term outcome of MWA is promising, although the high risk of local
recurrence after the operation should be considered when planning treatment.
PMID- 27487980
TI - Zn-biofortification enhanced nitrogen metabolism and photorespiration process in
green leafy vegetable Lactuca sativa L.
AB - BACKGROUND: Excessive rates of nitrogen (N) fertilizers may result in elevated
concentrations of nitrate (NO3- ) in plants. Considering that many programs of
biofortification with trace elements are being performed, it has become important
to study how the application of these elements affects plant physiology and,
particularly, N utilization in leaf crops. The main objective of the present
study was to determine whether the NO3- accumulation and the nitrogen use
efficiency was affected by the application of different doses of Zn in Lactuca
sativa plants. RESULTS: Zn doses in the range 80-100 umol L-1 produced an
increase in Zn concentration provoking a decrease of NO3- concentration and
increase of the nitrate reductase, glutamine synthetase and aspartate
aminotransferase activities, as well as the photorespiration processes. As
result, we observed an increase in reduced N, total N concentration and N
utilization efficiency. Consequently, at a dose of 80 umol L-1 of Zn, the amino
acid concentration increased significantly. CONCLUSION: Adequate Zn fertilization
is an important critical player in lettuce, especially at a dose of 80 umol L-1
of Zn, because it could result in an increase in the Zn concentration, a
reduction of NO3- levels and an increase the concentration of essential amino
acids, with all of them having beneficial properties for the human diet. (c) 2016
Society of Chemical Industry.
PMID- 27487981
TI - Calcium oxalate crystal production and density at different phenological stages
of soybean plants (Glycine max L.) from the southeast of the Pampean Plain,
Argentina.
AB - Glycine max L. (soybean) is one of the major crops of the world. Although the
process of biomineralisation has been reported in some organs of soybean, we now
report the description and quantification of calcium oxalate crystals in
vegetative and reproductive organs of soybean during its life cycle, as they act
as an important source of calcium to the soil, once the harvesting is finished.
Through diaphanisation, cross-sectioning, optical and scanning electron
microscopy analysis of the organs, morphology, size and location of the crystals
were identified. In addition, crystal density (n degrees crystals.mm-2 ) and the
input of crystals to soil (n degrees crystals.ha-1 ) were calculated. Soybean
produced prismatic calcium oxalate crystals in vegetative and reproductive
organs, generally associated with vascular bundles, resulting in a potencial
transfer to the soil of 81.4 x 107 crystals.ha-1 throughout its life cycle. Pods
were the organs with higher calcium oxalate crystal production (1112.7 +/- 384.6
crystals.mm-2 ), but with the smaller size (12.3 +/- 2.1 MUm long). However,
cotyledons were the organs that produce the larger crystals (21.3 +/- 3.5 MUm
long), but in lesser amounts (150.9 +/- 64.4 crystals.mm-2 ). In leaves, although
crystal size did not differ from vegetative to reproductive stage (14.5 +/- 4.2
and 14.5 +/- 4 MUm in length, respectively), the crystal density increased (293.2
and 409 crystals.mm-2 , respectively). These results will contribute to knowledge
of the amount of calcium oxalate crystals involved in the process of Ca recycling
through cultivated vegetation in fields from humid plains at medium latitudes,
which therefore have biological, botanical, biogeochemical and pedological
relevance.
PMID- 27487982
TI - The ginger component 6-shogaol prevents TNF-alpha-induced barrier loss via
inhibition of PI3K/Akt and NF-kappaB signaling.
AB - SCOPE: Anti-inflammatory properties of the ginger-derived pungent component 6
shogaol (6-SG) have been studied intensively in recent years. Purpose of this
study was to characterize the influence of 6-SG on inflammation-related
intestinal barrier dysfunction, especially its paracellular component. METHODS
AND RESULTS: The effect of 6-SG was studied in the human intestinal cell models
HT-29/B6 and Caco-2 either under control conditions or challenged by the pro
inflammatory cytokine tumor necrosis factor alpha (TNF-alpha).
Electrophysiological measurements, freeze-fracture electron microscopy, and
protein analyses were performed. 6-SG partially prevented both, the TNF-alpha
induced decrease in transepithelial resistance and the rise in fluorescein
permeability. By inhibiting phosphatidylinositol-3-kinase/Akt signaling 6-SG
prevented the TNF-alpha-induced increase in protein expression of claudin-2, a
channel-forming tight junction protein. In addition, the TNF-alpha-induced
disassembly of the sealing tight junction protein claudin-1 was attenuated, the
latter of which was due to TNF-alpha-triggered phosphorylation of nuclear factor
kappa light chain enhancer of activated B cells (NF-kappaB). CONCLUSION: 6-SG has
barrier-protective effects by affecting TNF-alpha-induced claudin-2 upregulation
and claudin-1 disassembly via inhibition of phoshatidylinositol-3-kinase/Akt and
nuclear factor kappa light chain enhancer of activated B-cell signaling.
Therefore, 6-SG-containing food might be beneficial for barrier preservation
during intestinal inflammation.
PMID- 27487984
TI - Therapeutic applications of conditioned medium from adipose tissue.
AB - For the past number of decades, adipose tissue has attracted significant interest
due to its complicated composition and versatile functions. Adipose tissue is no
longer considered to be just an energy-storing fat pad, but is also a key ring
player in interaction networks between various organs and tissues. A wide range
of factors released by adipose tissue are responsible for regulation of adipose
tissue and other distant target tissues and cells, such as kidneys, skeletal
muscle, the cardiovascular system and the immune system, in an auto-/paracrine
manner. A mixture of bioactive molecules makes up the conditioned medium of
adipose tissue. The beneficial role played by these bioactive molecules in
angiogenesis, wound healing, tissue regeneration and immunomodulation has been
demonstrated by various studies. Study of this conditioned medium helps deepen
our understanding of underlying mechanisms and broadens the potential for
therapeutic applications. In this review, we have aimed to improve fundamental
understanding of conditioned medium from adipose tissue and to summarize recent
efforts to study its therapeutic applications.
PMID- 27487983
TI - Subject-level reliability analysis of fast fMRI with application to epilepsy.
AB - PURPOSE: Recent studies have applied the new magnetic resonance encephalography
(MREG) sequence to the study of interictal epileptic discharges (IEDs) in the
electroencephalogram (EEG) of epileptic patients. However, there are no criteria
to quantitatively evaluate different processing methods, to properly use the new
sequence. METHODS: We evaluated different processing steps of this new sequence
under the common generalized linear model (GLM) framework by assessing the
reliability of results. A bootstrap sampling technique was first used to generate
multiple replicated data sets; a GLM with different processing steps was then
applied to obtain activation maps, and the reliability of these maps was
assessed. RESULTS: We applied our analysis in an event-related GLM related to
IEDs. A higher reliability was achieved by using a GLM with head motion confound
regressor with 24 components rather than the usual 6, with an autoregressive
model of order 5 and with a canonical hemodynamic response function (HRF) rather
than variable latency or patient-specific HRFs. Comparison of activation with IED
field also favored the canonical HRF, consistent with the reliability analysis.
CONCLUSION: The reliability analysis helps to optimize the processing methods for
this fast fMRI sequence, in a context in which we do not know the ground truth of
activation areas. Magn Reson Med 78:370-382, 2017. (c) 2016 International Society
for Magnetic Resonance in Medicine.
PMID- 27487985
TI - Bioimpedance Spectroscopy for Breast Cancer Related Lymphedema Assessment:
Clinical Practice Guidelines.
AB - With improved breast cancer survivorship, lymphedema of the arm is a growing
concern for many patients following treatment. Diagnosis and management of breast
cancer related lymphedema (BCRL) is often delayed due to low sensitivity
diagnostic techniques and a failure to incorporate BCRL assessments into standard
clinical practice. Bioimpedance spectroscopy (BIS) is an increasingly utilized
diagnostic technique that allows for the subclinical detection of BCRL, prior to
clinically evident disease. We provide a summary of the data supporting the early
detection and treatment of BCRL, a comparison of BCRL diagnostic modalities and
data supporting the utilization of BIS. Finally, clinical practice guidelines
will be provided to allow for the incorporation of BIS into the standard
management of breast cancer patients prior to and following locoregional and
systemic therapy. These clinical practice guidelines offer clinicians a method to
introduce bioimpedance into routine breast cancer care. With increasing focus on
BCRL, such protocols will allow for prospective evaluation of patients and early
diagnosis and treatment.
PMID- 27487986
TI - The effect of healthy dietary consumption on executive cognitive functioning in
children and adolescents: a systematic review.
AB - A systematic review was conducted to evaluate whether healthier dietary
consumption among children and adolescents impacts executive functioning. PubMed,
Education Resources Information Center, PsychINFO and Thomson Reuters' Web of
Science databases were searched, and studies of executive functioning among
children or adolescents aged 6-18 years, which examined food quality,
macronutrients and/or foods, were included. Study quality was also assessed. In
all, twenty-one studies met inclusion criteria. Among the twelve studies
examining food quality (n 9) or macronutrient intakes (n 4), studies examining
longer-term diet (n 6) showed positive associations between healthier overall
diet quality and executive functioning, whereas the studies examining the acute
impact of diet (n 6) were inconsistent but suggestive of improvements in
executive functioning with better food quality. Among the ten studies examining
foods, overall, there was a positive association between healthier foods (e.g.
whole grains, fish, fruits and/or vegetables) and executive function, whereas
less-healthy snack foods, sugar-sweetened beverages and red/processed meats were
inversely associated with executive functioning. Taken together, evidence
suggests a positive association between healthy dietary consumption and executive
functioning. Additional studies examining the effects of healthier food
consumption, as well as macronutrients, on executive functioning are warranted.
These studies should ideally be conducted in controlled environments and use
validated cognitive tests.
PMID- 27487987
TI - Characterization of lipopeptides produced by Bacillus licheniformis using liquid
chromatography with accurate tandem mass spectrometry.
AB - RATIONALE: The plant endophyte Bacillus licheniformis, isolated from leaves of
Vitis vinifera, was studied to individuate and characterize the presence of
bioactive lipopeptides having amino acidic structures. METHODS: Crude extracts of
liquid cultures were analyzed by ultra-high-performance liquid chromatography
(UHPLC) coupled to a quadrupole time-of-flight (QTOF) mass analyzer.
Chromatographic conditions were optimized in order to obtain an efficient
separation of the different isobaric lipopeptides, avoiding merged fragmentations
of co-eluted isomeric compounds and reducing possible cross-talk phenomena.
Composition of the amino acids was outlined through the interpretation of the
fragmentation behavior in tandem high-resolution mass spectrometry (HRMS/MS)
mode, which showed both common-class and peculiar fragment ions. Both [M + H](+)
and [M + Na](+) precursor ions were fragmented in order to differentiate some
isobaric amino acids, i.e. Leu/Ile. Neutral losses characteristic of the iso acyl
chain were also evidenced. RESULTS: More than 90 compounds belonging to the
classes of surfactins and lichenysins, known as biosurfactant molecules, were
detected. Sequential LC/HRMS/MS analysis was used to identify linear and cyclic
lipopeptides, and to single out the presence of a large number of isomers not
previously reported. Some critical issues related to the simultaneous selection
of different compounds by the quadrupole filter were highlighted and partially
solved, leading to tentative assignments of several structures. Linear
lichenysins are described here for the first time. CONCLUSIONS: The approach was
proved to be useful for the characterization of non-target lipopeptides, and
proposes a rationale MS experimental scheme aimed to investigate the difference
in amino acid sequence and/or in the acyl chain of the various congeners, when
standards are not available. Results expanded the knowledge about production of
linear and cyclic bioactive compounds from Bacillus licheniformis, clarifying the
structures of isomeric forms, and enabling the use of selected endophytes to
produce fungicides for eco-friendly biocontrol. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27487988
TI - Defining the origins of electron transfer at screen-printed graphene-like and
graphite electrodes: MoO2 nanowire fabrication on edge plane sites reveals
electrochemical insights.
AB - Molybdenum (di)oxide (MoO2) nanowires are fabricated onto graphene-like and
graphite screen-printed electrodes (SPEs) for the first time, revealing crucial
insights into the electrochemical properties of carbon/graphitic based materials.
Distinctive patterns observed in the electrochemical process of nanowire
decoration show that electron transfer occurs predominantly on edge plane sites
when utilising SPEs fabricated/comprised of graphitic materials. Nanowire
fabrication along the edge plane sites (and on edge plane like-sites/defects) of
graphene/graphite is confirmed with Cyclic Voltammetry, Scanning Electron
Microscopy (SEM) and Raman Spectroscopy. Comparison of the heterogeneous electron
transfer (HET) rate constants (k degrees ) at unmodified and nanowire coated SPEs
show a reduction in the electrochemical reactivity of SPEs when the edge plane
sites are effectively blocked/coated with MoO2. Throughout the process, the basal
plane sites of the graphene/graphite electrodes remain relatively uncovered;
except when the available edge plane sites have been utilised, in which case MoO2
deposition grows from the edge sites covering the entire surface of the
electrode. This work clearly illustrates the distinct electron transfer
properties of edge and basal plane sites on graphitic materials, indicating
favourable electrochemical reactivity at the edge planes in contrast to limited
reactivity at the basal plane sites. In addition to providing fundamental
insights into the electron transfer properties of graphite and graphene-like
SPEs, the reported simple, scalable, and cost effective formation of unique and
intriguing MoO2 nanowires realised herein is of significant interest for use in
both academic and commercial applications.
PMID- 27487989
TI - A large set of 26 new reference transcriptomes dedicated to comparative
population genomics in crops and wild relatives.
AB - We produced a unique large data set of reference transcriptomes to obtain new
knowledge about the evolution of plant genomes and crop domestication. For this
purpose, we validated a RNA-Seq data assembly protocol to perform comparative
population genomics. For the validation, we assessed and compared the quality of
de novo Illumina short-read assemblies using data from two crops for which an
annotated reference genome was available, namely grapevine and sorghum. We used
the same protocol for the release of 26 new transcriptomes of crop plants and
wild relatives, including still understudied crops such as yam, pearl millet and
fonio. The species list has a wide taxonomic representation with the inclusion of
15 monocots and 11 eudicots. All contigs were annotated using BLAST, prot4EST and
Blast2GO. A strong originality of the data set is that each crop is associated
with close relative species, which will permit whole-genome comparative
evolutionary studies between crops and their wild-related species. This large
resource will thus serve research communities working on both crops and model
organisms. All the data are available at http://arcad
bioinformatics.southgreen.fr/.
PMID- 27487990
TI - Adding energy minimization strategy to peptide-design algorithm enables better
search for RNA-binding peptides: Redesigned lambda N peptide binds boxB RNA.
AB - Our previously developed peptide-design algorithm was improved by adding an
energy minimization strategy which allows the amino acid sidechains to move in a
broad configuration space during sequence evolution. In this work, the new
algorithm was used to generate a library of 21-mer peptides which could
substitute for lambda N peptide in binding to boxB RNA. Six potential peptides
were obtained from the algorithm, all of which exhibited good binding capability
with boxB RNA. Atomistic molecular dynamics simulations were then conducted to
examine the ability of the lambda N peptide and three best evolved peptides, viz.
Pept01, Pept26, and Pept28, to bind to boxB RNA. Simulation results demonstrated
that our evolved peptides are better at binding to boxB RNA than the lambda N
peptide. Sequence searches using the old (without energy minimization strategy)
and new (with energy minimization strategy) algorithms confirm that the new
algorithm is more effective at finding good RNA-binding peptides than the old
algorithm. (c) 2016 Wiley Periodicals, Inc.
PMID- 27487991
TI - Therapeutic Value of Adeno Associated Virus as a Gene Therapy Vector for
Parkinson's Disease - A Focused Review.
AB - Although adeno-associated viral vectors have been studied for a long time, its
importance as a viable gene therapy strategy has been thrusted into the limelight
only in the recent years. Due to the admirable characteristics of these vectors,
their potential has been thoughtfully utilized in the treatment of several
neurodegenerative diseases. This mini-review focuses at recapitulating the
therapeutic advances of adeno-associated viral vectors in the treatment of
Parkinson's disease by studying the various animal model experiments and clinical
trials conducted since the advent of adeno-associated viral vector - based gene
therapy. Additionally, the chronological analysis of the studies in the review
makes it easier to understand the challenges and foretell the future prospects in
this field of therapeutics.
PMID- 27487992
TI - Patient intention and self-reported compliance in relation to emergency
department attendance after using an after hours GP helpline.
AB - OBJECTIVE: To determine ED attendance and compliance with GP advice following a
call to an after hours telephone triage and advice service. METHODS: A
descriptive study of users' of an after hours helpline self-reported ED
attendance and compliance with GP recommendation, based on routinely collected
service data and telephone survey results for 2783 callers in 2011-2012. The
outcome measure was self-reported health service utilisation following advice
from a GP on an after hours helpline. RESULTS: One-third of the sample - 934
callers - intended to visit the ED. Of these, 504 (54%, 95% CI 50.7%-57.2%)
reported taking other less urgent options. The GP assessment confirmed the
original intention for 224 callers (24%, 95% CI 21.2%-26.9%). However, 151
patients (16%, 95% CI 13.8%-18.6%) did attend the ED as they had originally
intended despite the GP's recommendation to seek less serious care, whereas a
further 55 patients (6%, 95% CI 4.4%-7.6%) assessed by the GP as requiring ED
care chose a less serious option. Fifty-five per cent of all callers who attended
ED did not intend to visit the ED prior to their call. The overall net result was
a small reduction in ED attendance compared with original intentions. CONCLUSION:
An after hours GP helpline may divert some callers intending to go to the ED to
other care. However, patient non-compliance may limit the capacity of telephone
triage and advice service to reduce demand for ED. Further research is needed to
better understand the effect of the service.
PMID- 27487994
TI - Why understanding the asthma chronic obstructive pulmonary disease overlap
syndrome (ACOS) is important to the clinician.
PMID- 27487993
TI - The causal relevance of body mass index in different histological types of lung
cancer: A Mendelian randomization study.
AB - Body mass index (BMI) is inversely associated with lung cancer risk in
observational studies, even though it increases the risk of several other
cancers, which could indicate confounding by tobacco smoking or reverse
causality. We used the two-sample Mendelian randomization (MR) approach to
circumvent these limitations of observational epidemiology by constructing a
genetic instrument for BMI, based on results from the GIANT consortium, which was
evaluated in relation to lung cancer risk using GWAS results on 16,572 lung
cancer cases and 21,480 controls. Results were stratified by histological
subtype, smoking status and sex. An increase of one standard deviation (SD) in
BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10).
This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P =
1.2 * 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse
trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified
analyses, a 1 SD increase in BMI was inversely associated with overall lung
cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher
BMI may increase the risk of certain types of lung cancer, in particular SQ and
SC carcinoma.
PMID- 27487995
TI - Ascorbic acid co-administration with artemisinin based combination therapies in
falciparum malaria.
PMID- 27487996
TI - NAT2 gene polymorphism: covert drug interaction causing phenytoin toxicity.
PMID- 27487997
TI - Why is the oral cholera vaccine not considered an option for prevention of
cholera in India? Analysis of possible reasons.
PMID- 27487998
TI - Zika virus: Indian perspectives.
AB - The emergence of Zika virus (ZiV), a mosquito borne Flavivirus like dengue (DEN)
and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries
have led to a global health emergency. Aedes aegypti is the major vector for ZiV.
Fast dissemination of this virus in different geographical areas posses a major
threat especially to regions where the population lacks herd immunity against the
ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on
current global scenario, epidemiology, biology, diagnostic challenges and
remedial measures for ZiVconsidering the Indian perspective.
PMID- 27488000
TI - In vitro effects of co-incubation of blood with artemether/lumefantrine & vitamin
C on the viscosity & elasticity of blood.
AB - BACKGROUND & OBJECTIVES: The antimalarial combination drug
artemether/lumefantrine has been shown to be effective against malaria parasite
through its haemolytic action. This drug is sometimes co-administered with
vitamin C in patients with malaria. Vitamin C is associated with antioxidant
properties which would be expected to protect against haemolytic effects of this
antimalarial drug. This study was designed to investigate in vitro effects of co
incubation of artemether/lumefantrine with vitamin C on the viscosity and
elasticity of blood. METHODS: Blood was collected from 12 healthy female
volunteers with normal haemoglobin genotype (HbAA). A Bioprofiler was used to
measure the viscosity and elasticity of untreated blood samples (control) and
samples exposed to artemether/lumefantrine (0.06/0.36 mg/ml) alone and with low
or high dose vitamin C (equivalent to adult doses of 100 or 500 mg). RESULTS:
artemether/lumefantrine significantly (p<0.05) reduced viscosity of blood from
4.72 +/- 0.38 to 3.78 +/- 0.17 mPa.s. Addition of vitamin C (500 mg) further
reduced blood viscosity to 2.67 +/- 0.05 mPa.s. The elasticity of blood was
significantly (p<0.05) reduced from 0.33 +/- 0.04 mPa.s to 0.24 +/- 0.03 mPa.s by
the antimalarial drug, and further reduced to 0.13 +/- 0.02 mPa.s in the presence
of vitamin C (500 mg). INTERPRETATION & CONCLUSIONS: Co-incubation of blood with
vitamin C and antimalarial combination drug potentiates the haemolytic effects of
the latter on reducing blood viscosity and elasticity in vitro. This may possibly
have implications in relation to haemolysis in patients receiving vitamin C
supplementation with artemether/lumefantrine during malaria therapy.
PMID- 27487999
TI - Shigellosis: Epidemiology in India.
AB - Shigellosis is one of the major causes of diarrhoea in India. The accurate
estimates of morbidity and mortality due to shigellosis are lacking, though it is
endemic in the country and has been reported to cause many outbreaks. The limited
information available indicates Shigella to be an important food- borne pathogen
in India. S. flexneri is the most common species, S. sonnei and non-agglutinable
Shigellae seem to be steadily surfacing, while S. dysenteriae has temporarily
disappeared from the northern and eastern regions. Antibiotic-resistant strains
of different Shigella species and serotypes have emerged all over the world.
Especially important is the global emergence of multidrug resistant Shigellae,
notably the increasing resistance to third generation cephalosporins and
fluoroquinolones, and also azithromycin. This calls for a continuous and strong
surveillance of antibiotic resistance across the country for periodic updation of
the local antibiograms. The prevention of shigellosis is desirable as it will
substantially reduce the morbidity associated with diarrhoea in the country.
Public health measures like provision of safe water and adequate sanitation are
of immense importance to reduce the burden of shigellosis, however, the provision
of resources to develop such an infrastructure in India is a complex issue and
will take time to resolve. Thus, the scientific thrust should be focused towards
development of a safe and affordable multivalent vaccine. this review is focused
upon the epidemiology, disease burden and the therapeutic challenges of
shigellosis in Indian perspective.
PMID- 27488001
TI - N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for
phenytoin intoxication in tuberculous meningitis or tuberculoma patients having
seizures - A pilot study.
AB - BACKGROUND & OBJECTIVES: Simultaneous administration of phenytoin and isoniazid
(INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures
results in higher plasma phenytoin level and thus phenytoin intoxication. N
acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH
metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The
present study was aimed to evaluate the effect of allelic variants of N
acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity
in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin
simultaneously. METHODS: Sixty patients with TBM or tuberculoma with seizures and
taking INH and phenytoin simultaneously for a minimum period of seven days were
included in study. Plasma phenytoin was measured by high performance liquid
chromatography. NAT2 gene polymorphism was studied using restriction fragment
length polymorphism and allele specific PCR. RESULTS: The patients were grouped
into those having phenytoin intoxication and those with normal phenytoin level,
and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic
analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2
gene studied, six mutations were found to be associated with phenytoin
intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A),
rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the
proportion of homozygous mutant was higher in phenytoin intoxicated group than in
phenytoin non-intoxicated group. INTERPRETATION & CONCLUSIONS: Homozygous mutant
allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin
intoxication among TBM or tuberculoma patients having seizures.
PMID- 27488002
TI - Interleukin-1beta (IL-1beta) & IL-4 gene polymorphisms in patients with systemic
lupus erythematosus (SLE) & their association with susceptibility to SLE.
AB - BACKGROUND & OBJECTIVES: Interleukin-1 (IL-1) is one of the pro-inflammatory
cytokines that plays a main role in the regulation of immune and inflammatory
responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates
balance between Th1 and Th2 immune responses. this study was undertaken to
investigate the IL-1beta and IL-4 genes polymorphisms in patients with systemic
lupus erythematosus (SLE) and also association between the polymorphisms and
susceptibility to SLE. METHODS: One hundred and sixty three SLE patients and 180
healthy controls were genotyped for the IL-4 VNTR (variable number tandem
repeat), IL-1beta C-511T and IL-1beta T-31C polymorphisms by polymerase chain
reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method.
RESULTS: The frequencies of CC genotype and C allele of the IL-1beta T-31C
polymorphism were significantly (P<0.01) lower in SLE patients than controls.
Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of IL-4 VNTR
polymorphism were significantly (P<0.05) higher in the SLE patients. No
association was observed between IL-1beta C-511T polymorphism and increased risk
of SLE. We observed increased frequency of CT and TT genotypes of IL-1beta C-511T
polymorphism in SLE patients with malar rash compared to SLE patients without
this manifestation. INTERPRETATION & CONCLUSIONS: The present findings suggest
that IL-1beta T-31C and IL-4 VNTR polymorphisms but not IL-1beta C-511T
polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes
of IL-1beta C-511T polymorphism were associated with SLE.
PMID- 27488003
TI - Image guided versus palpation guided core needle biopsy of palpable breast
masses: a prospective study.
AB - BACKGROUND & OBJECTIVES: Biopsy of palpable breast masses can be performed
manually by palpation guidance or under imaging guidance. Based on retrospective
studies, image guided biopsy is considered more accurate than palpation guided
breast biopsy; however, these techniques have not been compared prospectively. We
conducted this prospective study to verify the superiority and determine the size
of beneficial effect of image guided biopsy over palpation guided biopsy.
METHODS: Over a period of 18 months, 36 patients each with palpable breast masses
were randomized into palpation guided and image guided breast biopsy arms.
Ultrasound was used for image guidance in 33 patients and mammographic
(stereotactic) guidance in three patients. All biopsies were performed using 14
gauge automated core biopsy needles. Inconclusive, suspicious or imaging
histologic discordant biopsies were repeated. RESULTS: Malignancy was found in 30
of 36 women in palpation guided biopsy arm and 27 of 36 women in image guided
biopsy arm. Palpation guided biopsy had sensitivity, specificity, positive
predictive value (PPV) and negative predictive value (NPV) of 46.7, 100, 100,
27.3 per cent, respectively, for diagnosing breast cancer. Nineteen of 36 women
(52.8%) required repeat biopsy because of inadequate samples (7 of 19),
suspicious findings (2 of 19) or imaging-histologic discordance (10 of 19). On
repeat biopsy, malignancy was found in all cases of imaging-histologic
discordance. Image guided biopsy had 96.3 per cent sensitivity and 100 per cent
specificity. There was no case of inadequate sample or imaging-histologic
discordance with image guided biopsy. INTERPRETATION & CONCLUSIONS: Our results
showed that in palpable breast masses, image guided biopsy was superior to
palpation guided biopsy in terms of sensitivity, false negative rate and repeat
biopsy rates.
PMID- 27488004
TI - A clinicopathological study of primary central nervous system lymphomas & their
association with Epstein-Barr virus.
AB - BACKGROUND & OBJECTIVES: Primary central nervous system lymphomas (PCNSLs) are
relatively uncommon, accounting for 2-3 per cent of primary brain tumours.
Majority of these are diffuse large B cell lymphomas (DLBCL) occurring both in
immunocompromised and immunocompetent patients. We undertook this study to
classify PCNSL into germinal centre (GC) and non-germinal centre (NGC) type based
on Hans classification and to find the role of Epstein-Barr virus (EBV) in
pathogenesis both by conventional immunohistochemistry (IHC) and chromogenic in
situ hybridization (CISH). METHODS: The consecutive cases of PCNSL during a 10
years period were analysed by IHC for CD45, CD20, CD3, B-cell lymphoma 2 and 6
(Bcl-2 and Bcl-6), B-cell specific octamer binding protein-1 (BOB-1), multiple
myeloma oncogene-1 (MUM-1), EBV latent-membrane protein 1 (LMP-1), cyclin-D1,
CD10, CD5 and CD23, as well as by CISH for EBV. RESULTS: During a period of 10
years, 65 PCNSL were diagnosed which comprised 0.69 per cent (65/9476) of all
intracranial tumours. The mean age of presentation was 49 yr with sex ratio (M:F)
of 1.4:1. Most common location was supratentorial region with predominant
involvement of frontal lobe. Single lesions were seen in 38 (58.4%) and
multifocal lesions in 27 (41.5%) patients. None of the patients were
immunocompromised. All cases were B cell immunophenotype and were DLBCL except
one case of follicular lymphoma. According to Hans classification, majority of
them were NGC (n=51, 79.6%) and 13 (20.3%) were GC type. Bcl-2 expression was
noted in 34 (52.3%) tumours. EBV was positive in three (4.6%) cases; two were
detected both by IHC and CISH and one case by CISH only. INTERPRETATION &
CONCLUSIONS: In Indian population, PCNSL occurs mainly in immunocompetent
patients, and a decade earlier than in western population. Immunophenotyping
revealed that all cases were DLBCL with predominance of NGC type. No prognostic
difference was seen between GC and NGC DLBCL. Association of EBV was rare and
this virus was possibly not involved in the pathogenesis of PCNSL in
immunocompetent individuals. CISH was an easy, economical and less cumbersome
method for detection of EBV in PCNSL.
PMID- 27488005
TI - Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in
Indian males with congenital bilateral absence of vas deferens & renal anomalies.
AB - BACKGROUND & OBJECTIVES: The role of cystic fibrosis transmembrane conductance
regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens
and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report
the cases of five Indian males with CBAVD-URA. The objective was to evaluate the
presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female
partners of these males were also screened for cystic fibrosis (CF) carrier
status. METHODS: Direct DNA sequencing of CFTR gene was carried out in five
Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy
controls (n=32) were also screened. RESULTS: Three potential regulatory CFTR gene
variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T
mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants
(c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T),
four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and
seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041
71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected
in infertile men having CBAVD and renal anomalies Interpretation & conclusions:
Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR
gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR
gene mutation screening may be offered to CBAVD-URA men and their female partners
undergoing ICSI. Further studies need to be done in a large sample to confirm the
findings.
PMID- 27488006
TI - Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute
lung injury/acute respiratory distress syndrome.
AB - BACKGROUND & OBJECTIVES: Despite advances in therapy and overall medical care,
acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management
remains a problem. Hence the objective of this study was to develop a rat model
that mimics human ALI/ARDS. METHODS: Four groups of Wistar rats, 48 per group
were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg)
dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250
MUl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2
mg/kg) dissolved in NS and iv OA (100 MUl/kg) and (iv) control group: IT NS and
iv BSA. From each group at set periods of time various investigations like chest
x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential
cell count, total protein count and cytokine levels in bronchoalveolar lavage
fluid (BALF), lung wet/dry weight ratio and histopathological examination were
done. RESULTS: It was noted that the respiratory rate, and tumour necrosis factor
alpha (TNF-alpha) levels were significantly higher at 4 h in the dual hit group
as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were
significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA
at 8 h and control (at all time intervals) group. IL-1beta levels were
significantly higher in LPS and dual hit groups at all time intervals, but not in
OA and control groups. The injury induced in dual hit group was earlier and more
sustained as compared to LPS and OA alone. INTERPRETATION & CONCLUSIONS: The lung
pathology and changes in respiration functions produced by the dual hit model
were closer to the diagnostic criteria of ALI/ARDS in terms of clinical
manifestations and pulmonary injury and the injury persisted longer as compared
to LPS and OA single hit model. Therefore, the ARDS model produced by the dual
hit method was closer to the diagnostic criteria of ARDS in terms of clinical
manifestations and pulmonary injury.
PMID- 27488007
TI - Frequency of Mi(a) antigen: A pilot study among blood donors.
AB - The Miltenberger (Mi) classes represent a group of phenotypes for red cells that
carry low frequency antigens associated with the MNSs blood group system. This
pilot study was aimed at determining the Mia antigen positivity in the blood
donor population in a tertiary care hospital in New Delhi, India. The study was
performed between June to August 2014 on eligible blood donors willing to
participate. Antigen typing was performed using monoclonal anti-Mia antiserum by
tube technique. Only one of the 1000 blood donors (0.1%) tested was found to be
Mia antigen positive. the Mia antigen can, therefore, be considered as being rare
in the Indian blood donor population.
PMID- 27488008
TI - Baseline characteristics of HIV & hepatitis B virus (HIV/HBV) co-infected
patients from Kolkata, India.
AB - BACKGROUND & OBJECTIVES: Hepatitis B virus (HBV) and HIV co-infection has
variable prevalence worldwide. In comparison to HBV mono-infection, the course of
chronic HBV infection is accelerated in HIV/HBV co-infected patients. the present
study was carried out to analyse the baseline characteristics (clinical,
biochemical, serological and virological) of treatment naive HIV/HBV co-infected
and HIV mono-infected patients. METHODS: Between July 2011 and January 2013, a
total number of 1331 HIV-seropositive treatment naive individuals, enrolled in
the ART Centre of Calcutta School of Tropical Medicine, Kolkata, India, were
screened for hepatitis B surface antigen (HBsAg). A total of 1253 HIV mono
infected and 78 HIV/HBV co-infected patients were characterized. The co-infected
patients were evaluated for HBeAg and anti-HBe antibody by ELISA. HIV RNA was
quantified for all co-infected patients. HBV DNA was detected and quantified by
real time-PCR amplification followed by HBV genotype determination. RESULTS:
HIV/HBV co-infected patients had proportionately more advanced HIV disease (WHO
clinical stage 3 and 4) than HIV mono-infected individuals (37.1 vs. 19.9%). The
co-infected patients had significantly higher serum bilirubin, alanine
aminotransferase (ALT), alkaline phosphatase and ALT/platelet ratio index (APRI).
CD4 count was non-significantly lower in co-infected patients. Majority (61.5%)
were HBeAg positive with higher HIV RNA (P<0.05), HBV DNA (p<0.001) and APRI
(p<0.05) compared to those who were HBeAg negative. HBV/D was the predominant
genotype (73.2%) and D2 (43.7%) was the commonest subgenotype. INTERPRETATION &
CONCLUSIONS: HIV/HBV co-infected patients had significantly higher serum
bilirubin, ALT, alkaline phosphatase and lower platelet count. HBeAg positive co
infected patients had higher HIV RNA and HBV DNA compared to HBeAg negative co
infected patients. Prior to initiation of antiretroviral treatment (ART) all
patients should be screened for HBsAg to initiate appropriate ART regimen.
PMID- 27488009
TI - Subinhibitory concentration of ciprofloxacin targets quorum sensing system of
Pseudomonas aeruginosa causing inhibition of biofilm formation & reduction of
virulence.
AB - BACKGROUND & OBJECTIVES: Biofilms formed by pseudomonas aeruginosa lead to
persistent infections. Use of antibiotics for the treatment of biofilm induced
infection poses a threat towards development of resistance. Therefore, the
research is directed towards exploring the property of antibiotics which may
alter the virulence of an organism besides altering its growth. The aim of this
study was to evaluate the role of subinhibitory concentration of ciprofloxacin
(CIP) in inhibiting biofilm formation and virulence of P. aeruginosa. METHODS:
Antibiofilm potential of subinhibitory concentration of CIP was evaluated in
terms of log reduction, biofilm forming capacity and coverslip assay. P.
aeruginosa isolates (grown in the presence and absence of sub-MIC of CIP) were
also evaluated for inhibition in motility, virulence factor production and quorum
sensing (QS) signal production. RESULTS: Sub-minimum inhibitory concentration
(sub-MIC) of CIP significantly reduced the motility of P. aeruginosa stand and
strain and clinical isolates and affected biofilm forming capacity. Production of
protease, elastase, siderophore, alginate, and rhamnolipid was also significantly
reduced by CIP. INTERPRETATION & CONCLUSIONS: Reduction in virulence factors and
biofilm formation was due to inhibition of QS mechanism which was indicated by
reduced production of QS signal molecules by P. aeruginosa in presence of
subinhibitory concentration of CIP.
PMID- 27488010
TI - Isolation & characterization of Brucella melitensis isolated from patients
suspected for human brucellosis in India.
AB - BACKGROUND & OBJECTIVES: Brucellosis is endemic in the southern part of India. A
combination of biochemical, serological and molecular methods is required for
identification and biotyping of Brucella. The present study describes the
isolation and biochemical, molecular characterization of Brucella melitensis from
patients suspected for human brucellosis. METHODS: The blood samples were
collected from febrile patients suspected to have brucellosis. A total of 18
isolates were obtained from 102 blood samples subjected to culture. The
characterization of these 18 isolates was done by growth on Brucella specific
medium, biochemical reactions, CO2 requirement, H2S production, agglutination
with A and M mono-specific antiserum, dye sensitivity to basic fuchsin and
thionin. Further, molecular characterization of the isolates was done by
amplification of B. melitensis species specific IS 711 repetitive DNA fragment
and 16S (rRNA) sequence analysis. PCR-restriction fragment length polymorphism
(RFLP) analysis of omp2 locus and IS711 gene was also done for molecular
characterization. RESULTS: All 102 suspected samples were subjected to bacteria
isolation and of these, 18 isolates could be recovered on blood culture. The
biochemical, PCR and PCR-RFLP and 16s rRNA sequencing revealed that all isolates
were of B. melitensis and matched exactly with reference strain B. melitensis
16M. INTERPRETATION & CONCLUSIONS: The present study showed an overall isolation
rate of 17.64 per cent for B. melitensis. There is a need to establish facilities
for isolation and characterization of Brucella species for effective clinical
management of the disease among patients as well as surveillance and control of
infection in domestic animals. Further studies are needed from different
geographical areas of the country with different level of endemicity to plan and
execute control strategies against human brucellosis.
PMID- 27488011
TI - M types & toxin gene profile of group A streptococci isolated from children in
Dibrugarh district of Assam, India.
PMID- 27488012
TI - Hajdu-Cheney syndrome - a rare cause of micrognathia.
PMID- 27488013
TI - Giant virilizing adrenocarcinoma: Rare presentation & management dilemma.
PMID- 27488014
TI - Tuberous sclerosis with bilateral giant renal angiomyolipomas.
PMID- 27488015
TI - M2L4 coordination capsules with tunable anticancer activity upon guest
encapsulation.
AB - Metallosupramolecular cages and capsules have gained increasing popularity as
both molecular containers and anticancer agents. For successful combination of
these properties a thorough analysis of the effect of guest encapsulation on the
host's cytotoxic properties is highly required. Here we report on the
cytotoxicity modulation of Pt(ii) and Pd(ii)-linked M2L4 coordination capsules
upon encapsulation of guest molecules such as pyrene and caffeine. The anticancer
activity of the capsules against various human cancer cells (HT-29, T-24, HL-60
and its resistant counterparts HL-60/Dox and HL-60/CDDP) significantly altered
upon the guest encapsulation. The encapsulation of pyrene molecules causes a
decrease in the cytotoxicity of the Pt(ii) capsule, which is stronger than that
of the Pd(ii) capsule. The cytotoxicities of the caffeine containing capsules are
lower than that of the empty capsules (except for HL-60), but still superior to
cisplatin under the same conditions. The observed trends in the anticancer
activity of the capsules and their host-guest complexes correlate with their
different stabilities toward glutathione, estimated by NMR-based kinetic
experiments. Mechanistic insights into the observed cytotoxicities are obtained
by fluorescence microscopy imaging of tumor cells treated with the capsules and
their pyrene complexes. The data suggest the glutathione-triggered disassembly of
the capsular structures as a potential activation pathway for their
cytotoxicities.
PMID- 27488016
TI - Baseline correction of AFM force curves in the force-time representation.
AB - This note reports on the proper correction of force data acquired with an atomic
force microscope (AFM). The force-time representation is hereby used to obtain
the correction factors for the overall offset and slope for a single force-time
curve, as the initial force, F0 = F(t0 ), and the rate of change in the force
per unit of time, dF/dt, respectively. The report shows that a complete set of
force data, including the approach, delay and retraction regions, can be
simultaneously corrected in the force-time representation by subtracting the line
CLt = F0 + dF/dt.t to the experimental data. The method described here
outperforms the one commonly employed in the correction of AFM force curves and
highlights the convenience of using the force-time representation for force data
processing wherein the artifactual behavior can be expressed as a single,
differentiable function of time.
PMID- 27488017
TI - Analysis of aflatoxins in traditional Chinese medicines: Classification of
analytical method on the basis of matrix variations.
AB - A classification system for analytical methods was developed for the first time
to determine the presence of aflatoxins B1, B2, G1 and G2 in traditional Chinese
medicines (TCMs) based on different matrix types using ultra-performance liquid
chromatography-tandem mass spectrometry. A useful characteristic of the approach
was that the TCMs could be systematically divided into four categories (i.e.,
volatile oils, proteins, polysaccharides and fatty oils) depending on the matrix
types. The approach concluded that different types of TCMs required different
optimal sample preparation procedures. Based on the optimized analytical
conditions, the limits of detection and quantification, average recoveries and
linearity of four aflatoxins were determined and conformed to research limits. Of
22 TCMs samples, 14 samples were contaminated with at least one type aflatoxin at
concentrations ranging from 0.2 to 7.5 MUg/kg, and the average contents of
aflatoxins were significantly different for the different matrix types. Moreover,
we found a potential link between the contamination levels of aflatoxins and
matrix types. TCMs containing fatty oils were the most susceptible to
contamination by aflatoxins and followed by TCMs containing polysaccharides and
proteins; TCMs containing abundant amounts of volatile oils were less prone to
contamination.
PMID- 27488019
TI - Induction of pulmonary antibodies against oxidized lipids in mice exposed to
cigarette smoke.
AB - BACKGROUND: Chronic cigarette smoke exposure is known to activate the adaptive
immune system; however, the functional role of these processes is currently
unknown. Given the role of oxidized lipids in driving innate inflammatory
responses to cigarette smoke, we investigated whether an adaptive immune response
against damaged lipids was induced following chronic cigarette smoke exposure.
METHODS AND RESULTS: Using a well-established mouse model, we showed that
cigarette smoke exposure led to a progressive increase in pulmonary antibodies
against oxidized low-density lipoprotein (OxLDL). Functionally, we found that
intranasal delivery of an antibody against oxidized phosphatidylcholine (anti
OxPC; clone E06) increased lipid and particle uptake by pulmonary macrophages
without exacerbating cigarette smoke-induced neutrophilia. We also found that
anti-OxPC treatment increased particle uptake following smoking cessation.
Finally, the frequency of pulmonary macrophages with internalized particles was
increased after prolonged smoke exposure, at which time lung anti-OxPC responses
were highest. CONCLUSIONS: Altogether, this is the first report to demonstrate a
non-pathogenic, and possibly protective, function of a newly identified
autoantibody induced by chronic cigarette smoke exposure.
PMID- 27488020
TI - Treatment of breast cancer 2 (BRCA2)-mutant follicular dendritic cell sarcoma
with a poly ADP-ribose polymerase (PARP) inhibitor: a case report.
AB - BACKGROUND: Follicular dendritic cell sarcoma is a rare tumour with clinical
behaviour covering a spectrum from indolent to aggressive disease. Treatment
recommendations are currently based on case reports and small series describing
combinations of surgery, chemotherapy and radiotherapy providing the best patient
outcomes. Recent knowledge on molecular aberrations in this disease have not yet
impacted on therapeutic decisions. CASE PRESENTATION: We describe a case of
progressive follicular dendritic cell sarcoma of the lung and pleura, treated
based on knowledge of the tumour's molecular aberrations. The patient was
initially treated with surgery, chemotherapy and radiotherapy and developed
disease progression. Mutation testing by Caris molecular intelligence
demonstrated a breast cancer 2 gene mutation and further treatment with
carboplatin and veliparib achieved disease stabilisation. CONCLUSION:
Understanding of the molecular profile of rare tumours is key to improve
therapeutic decision making and patient outcomes.
PMID- 27488022
TI - Transgenerational transmission of pregestational and prenatal experience:
maternal adversity, enrichment, and underlying epigenetic and environmental
mechanisms.
AB - Transgenerational transmission refers to positive and negative adaptations in
brain function and behavior that affect following generations. In this paper,
empirical findings regarding the transgenerational transmission of maternal
adversity during three critical periods - childhood, pregestational adulthood and
pregnancy - will be reviewed in terms of pregnancy outcomes, maternal care,
offspring behavior and development, and physiological functioning. Research on
the transgenerational transmission of enrichment and the implications for
interventions to ameliorate the consequences of adversity will also be presented.
In the final section, underlying epigenetic and environmental mechanisms that
have been proposed to explain how experience is transferred across generations
through transgenerational transmission will be reviewed. Directions for future
research are suggested throughout.
PMID- 27488021
TI - Assembly of Bak homodimers into higher order homooligomers in the mitochondrial
apoptotic pore.
AB - In mitochondrial apoptosis, Bak is activated by death signals to form pores of
unknown structure on the mitochondrial outer membrane via homooligomerization.
Cytochrome c and other apoptotic factors are released from the intermembrane
space through these pores, initiating downstream apoptosis events. Using chemical
crosslinking and double electron electron resonance (DEER)-derived distance
measurements between specific structural elements in Bak, here we clarify how the
Bak pore is assembled. We propose that previously described BH3-in-groove
homodimers (BGH) are juxtaposed via the 'alpha3/alpha5' interface, in which the C
termini of helices alpha3 and alpha5 are in close proximity between two
neighboring Bak homodimers. This interface is observed concomitantly with the
well-known 'alpha6:alpha6' interface. We also mapped the contacts between Bak
homodimers and the lipid bilayer based on EPR spectroscopy topology studies. Our
results suggest a model for the lipidic Bak pore, whereby the mitochondrial
targeting C-terminal helix does not change topology to accommodate the lining of
the pore lumen by BGH.
PMID- 27488023
TI - Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study.
PMID- 27488024
TI - Revealing Hidden Schatzki Rings Using the Bolster Technique.
PMID- 27488026
TI - Immature Oocytes from Unprimed Juvenile Mice Become a Valuable Source for Embryo
Production When Using C-Type Natriuretic Peptide as Essential Component of
Culture Medium.
AB - C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor 2
(NPR2) play a paramount role in the maintenance of oocyte meiotic arrest in
antral follicles via the regulation of the intra-oocyte levels of cyclic
guanosine monophosphate and cyclic adenosine monophosphate. We investigated the
potential of CNP 1) to maintain oocyte meiotic arrest during a prolonged
prematuration culture and 2) to sustain acquisition of developmental competence
of immature cumulus-oocyte complexes (COCs). Compact COCs were collected from
small antral follicles of prepubertal unprimed mice and placed in prematuration
culture under different CNP-supplemented media conditions. A preliminary analysis
showed a dose-dependent effect of CNP on the maintenance of meiotic arrest. A
dose of 25 nM maintained oocytes under meiotic arrest for 24 h, and this period
was extended to 48 h in the presence of estradiol. Analysis of transzonal
projections of COCs cultured with CNP indicated that oocyte-cumulus connections
were well preserved after the prolonged prematuration culture. Furthermore, CNP
medium supplemented with FSH and GDF9 promoted oocyte growth and induced a shift
in oocyte chromatin configuration from a predominantly dispersed to a condensed
configuration. Following in vitro maturation, oocytes cultured under CNP were
capable of extruding the first polar body at a high rate (around 80%). Blastocyst
formation was significantly improved when oocytes were cultured under CNP
supplemented medium containing FSH and GDF9. This study reports for the first
time a prolonged prematuration culture system, with CNP as the pivotal factor,
that can efficiently maintain oocytes retrieved from unprimed prepubertal mice
under meiotic arrest while promoting their acquisition of developmental
competence.
PMID- 27488027
TI - Downregulation of miR-199a-5p Disrupts the Developmental Potential of In Vitro
Fertilized Mouse Blastocysts.
AB - Although in vitro fertilization (IVF), one of the most effective and successful
assisted reproductive technologies, is widely used for treating infertility and
in animal breeding, increasing evidence indicates that IVF offspring are linked
to various short- or long-term consequences. Erroneous epigenetic modifications
induced by IVF are suspected of contributing to these consequences. Among these
epigenetic modifications, microRNAs may affect embryo implantation and early
postimplantation development. Here, we performed comparative microRNA profiling
between in vivo-fertilized (IVO group) and in vitro-fertilized (IVF group) mouse
embryos at Embryonic Day 3.5 (E3.5) and E7.5. Our dynamic analyses showed that
the dysregulated microRNAs were mainly associated with the regulation of genes
involved in carcinogenesis, genetic information processing, glucose metabolism,
cytoskeleton organization, and neurogenesis. Further analysis showed that miR
199a-5p was consistently downregulated in IVF embryos compared with their IVO
counterparts. Through gain- and loss-of-function experiments, we demonstrated
that IVF-induced downregulation of miR-199a-5p results in a higher glycolytic
rate and lower developmental potential of IVF blastocysts, including cell lineage
misallocation and lower fetal survival post implantation. Therefore, preventing
downregulation of miR-199a-5p may become an effective strategy for improving the
development of IVF peri-implantation embryos in the future.
PMID- 27488025
TI - Daptomycin for the treatment of major gram-positive infections after cardiac
surgery.
AB - BACKGROUND: Infection is a main cause of morbidity and mortality after heart
surgery, with multi-resistant pathogens increasingly representing a challenge.
Daptomycin provides bactericidal activity against gram-positive organisms that
are resistant to standard treatment including vancomycin. METHODS: A cohort of
cardiac surgical patients, treated with daptomycin for major infection at two
tertiary care centers, were retrospectively studied with a particular focus on
the type of infection, causative pathogens and co-infections, daptomycin dosage,
adverse events and outcome in order to provide evidence for the efficiency and
safety of daptomycin in a distinct high-risk patient population. RESULTS: Sixty
five patients (87.7 % males, 60.4 +/- 13.5 years) who had undergone aortic
surgery (20.0 %), ventricular assist device (VAD) implantation (21.5 %), combined
procedures (21.5 %), coronary artery bypass grafting (12.3 %), isolated valve
surgery (15.4 %) and heart transplantation (7.7 %) were diagnosed with catheter
related infection (26.1 %), valve endocarditis (18.8 %), sternal wound (13.0 %),
VAD-associated (11.6 %), cardiac implantable electrophysiological device (CIED)
associated (4.1 %), respiratory tract (4.3 %), bloodstream (4.3 %) and other
infection (4.3 %). In 13.0 %, no focus of infection was identified though
symptoms of severe infection were present. The most frequent pathogens were
Staphylococcus epidermidis (30.4 %), Staphylococcus aureus (23.1 %) and
Enterococcus species (10.1 %). Daptomycin doses ranging from 3 mg/kg every 48 h
to 10 mg/kg every 24 h were administered for 15.4 +/- 11.8 days. 87.0 % of the
cases were classified as success, 7.2 % as treatment failure and 5.8 as non
evaluable. Adverse events were limited to one case of mild and one case of
moderate neutropenia with recovery upon termination of treatment. CONCLUSION:
Daptomycin proved safe and effective in major infection in high-risk cardiac
surgical patients.
PMID- 27488028
TI - Deficiency of SPATA46, a Novel Nuclear Membrane Protein, Causes Subfertility in
Male Mice.
AB - Teratozoospermia is generally associated with clinical infertility. Despite
numerous studies, the molecular mechanisms underlying male infertility are still
poorly understood. In the present study, we demonstrated that deletion of
Spata46, a gene encoding a novel protein of unknown function found in mouse
testis, was responsible for male subfertility, and the cause of subfertility was
characterized as abnormal sperm head shape and a failure of sperm-egg fusion. We
also demonstrated that SPATA46 was expressed predominantly in condensed
spermatids, with a highly specific localization restricted to the subacrosomal
area; the protein is located at the nuclear membrane due to a transmembrane
region in the N-terminus of the protein. At the subcellular level, SPATA46
deficient condensed spermatids displayed structural defects consisting of a
discontinuous nuclear envelope and a cavity in the nucleus associated with an
abnormal nuclear shape. Additionally, in vitro, we determined that the absence of
SPATA46 led to accumulation of sperm around the perivitelline space of eggs, and
the same phenomenon was also observed for natural sperm incubated with an anti
SPATA46 antibody, suggesting functional relevance of SPATA46 for sperm-egg
fusion. Taken together, these results indicated that SPATA46 is a novel protein
involved in reshaping of the sperm head and sperm-egg fusion.
PMID- 27488029
TI - Characterizing the Spermatogonial Response to Retinoic Acid During the Onset of
Spermatogenesis and Following Synchronization in the Neonatal Mouse Testis.
AB - Retinoic acid (RA), the active metabolite of vitamin A, is known to be required
for the differentiation of spermatogonia. The first round of spermatogenesis
initiates in response to RA and occurs in patches along the length of the
seminiferous tubule. However, very little is known about the individual
differentiating spermatogonial populations and their progression through the cell
cycle due to the heterogeneous nature of the onset of spermatogenesis. In this
study, we utilized WIN 18,446 and RA as tools to generate testes enriched with
different populations of spermatogonia to further investigate 1) the
undifferentiated to differentiating spermatogonial transition, 2) the progression
of the differentiating spermatogonia through the cell cycle, and 3) Sertoli cell
number in response to altered RA levels. WIN 18,446/RA-treated neonatal mice were
used to determine when synchronous S phases occurred in the differentiating
spermatogonial population following treatment. Five differentiating
spermatogonial S phase windows were identified between spermatogonial
differentiation and formation of preleptotene spermatocytes. In addition, a
slight increase in Sertoli cell number was observed following RA treatment,
possibly implicating a role for RA in Sertoli cell cycle progression. This study
has enhanced our understanding of the spermatogonial populations present in the
neonatal testis during the onset of spermatogenesis by mapping the cell cycle
kinetics of both the undifferentiated and the differentiating spermatogonial
populations and identifying the precise timing of when specific individual
differentiating spermatogonial populations are enriched within the testis
following synchrony, thus providing an essential tool for further study of the
differentiating spermatogonia.
PMID- 27488031
TI - Retinoic Acid Regulates Calcium Signaling to Promote Mouse Ovarian Granulosa Cell
Proliferation.
AB - Normal development of ovarian follicles is critical for female reproduction and
endocrine function. We have identified retinoic acid (RA) and the RA-degrading
enzyme CYP26B1 as regulators of ovarian follicle development and showed that RA
and a CYP26 inhibitor stimulated ovarian granulosa cell proliferation. The
mechanism underpinning RA-dependent proliferation, however, is not known. The
current study was designed to examine the role of intracellular calcium (Ca2+)
signaling in mediating the effects of RA on primary mouse granulosa cell
proliferation. In single-cell Ca2+ imaging experiments, treatment of cultured
granulosa cells with RA increased the steady-state Ca2+ content of the
endoplasmic reticulum (ER) stores. This correlated with increased store-operated
Ca2+ entry (SOCE) and enhanced inositol 1,4,5-trisphosphate receptor (IP3R)
dependent Ca2+ release. In proliferation assays, RA treatment or Cyp26b1
knockdown stimulated proliferation, whereas Cyp26b1 overexpression inhibited
proliferation. When RA was given together with 2-aminoethoxydiphenylborane (2
APB), a blocker of IP3R-dependent ER Ca2+ release and SOCE, with xestospongin C,
a selective IP3R- receptor antagonist, or with 3,5-bis (trifluoromethyl)pyrazole
(BTP-2), a specific SOCE blocker, the stimulatory effect of RA on cell
proliferation was abolished. Further investigation showed that treatment with 2
APB or BTP-2 inhibited RA induction of RA response element (RARE) activation in
granulosa cells, confirming an important role for Ca2+ signaling in mediating RA
actions. Overall, these data support a model in which RA regulates ovarian
follicle development by stimulating granulosa cell proliferation and that this
stimulatory effect is at least in part driven by the modulation of Ca2+
signaling.
PMID- 27488030
TI - Reactive Oxygen Stimulation of Interleukin-6 Release in the Human Trophoblast
Cell Line HTR-8/SVneo by the Trichlorethylene Metabolite S-(1,2-Dichloro)-l
Cysteine.
AB - Trichloroethylene (TCE) is a common environmental pollutant associated with
adverse reproductive outcomes in humans. TCE intoxication occurs primarily
through its biotransformation to bioactive metabolites, including S-(1,2
dichlorovinyl)-l-cysteine (DCVC). TCE induces oxidative stress and inflammation
in the liver and kidney. Although the placenta is capable of xenobiotic
metabolism and oxidative stress and inflammation in placenta have been associated
with adverse pregnancy outcomes, TCE toxicity in the placenta remains poorly
understood. We determined the effects of DCVC by using the human extravillous
trophoblast cell line HTR-8/SVneo. Exposure to 10 and 20 MUM DCVC for 10 h
increased reactive oxygen species (ROS) as measured by carboxydichlorofluorescein
fluorescence. Moreover, 10 and 20 MUM DCVC increased mRNA expression and release
of interleukin-6 (IL-6) after 24-h exposure, and these responses were inhibited
by the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid and by
treatments with antioxidants (alpha-tocopherol and deferoxamine), suggesting that
DCVC-stimulated IL-6 release in HTR-8/SVneo cells is dependent on beta-lyase
metabolic activation and increased generation of ROS. HTR-8/SVneo cells exhibited
decreased mitochondrial membrane potential at 5, 10, and 20 MUM DCVC at 5, 10,
and 24 h, showing that DCVC induces mitochondrial dysfunction in HTR-8/Svneo
cells. The present study demonstrates that DCVC stimulated ROS generation in the
human placental cell line HTR-8/SVneo and provides new evidence of mechanistic
linkage between DCVC-stimulated ROS and increase in proinflammatory cytokine IL
6. Because abnormal activation of cytokines can disrupt trophoblast functions
necessary for placental development and successful pregnancy, follow-up
investigations relating these findings to physiologic outcomes are warranted.
PMID- 27488032
TI - The Effect of Coumestrol on Progesterone and Prostaglandin Production in the
Mare: In Vitro and In Vivo Studies.
AB - Coumestrol (Cou) is a plant-derived phytoestrogen that induces various
pathologies in the female reproductive tract. Although effects of phytoestrogens
on reproductive function in other species are well documented, their influence on
progesterone (P4) and prostaglandin (PG) secretion in the mare is unknown. The
aim of this study was to determine if Cou directly affects P4 and PG
concentrations (in vivo) and endometrial PG secretion (in vitro) in the mare. In
experiment 1, the mares (n = 4) were fed for 14 days on a diet containing
increasing proportions of alfalfa pellets (250 g-1 kg/day). An additional 4 mares
were fed a standard diet (control group). Sequential blood samples were obtained
for 8 h after feeding on Days 13 and 14 (1 kg/day alfalfa pellets). Feeding the
mares alfalfa pellets up-regulated PGE2 and 13,14-dihydro-15-ketoprostaglandin
F2alpha (PGFM) and down-regulated P4 in the blood plasma compared to those in the
control group (P < 0.05). In experiment 2, epithelial and stromal cells were
exposed to E2 (10-9 M) or Cou (10-8 M) for 24 h. In the in vitro study, Cou
increased PG secretion in epithelial and stromal cells (P < 0.05). In both types
of endometrial cells, Cou up-regulated PTGS-2 protein expression (P < 0.05).
Moreover, PGES and PGFS proteins were up-regulated by Cou in epithelial cells (P
< 0.01). These results indicate that Cou can disturb reproductive function by
affecting reproductive hormone secretion and altering the endometrial milieu
through PG stimulation. Coumestrol therefore may impair physiologic regulation of
the estrous cycle and early pregnancy.
PMID- 27488033
TI - Sexually Dimorphic Gene Expression in Bovine Conceptuses at the Initiation of
Implantation.
AB - In cattle, maternal recognition of pregnancy occurs on Day 16 via secretion of
interferon tau (IFNT) by the conceptus. The endometrium can distinguish between
embryos with different developmental competencies. In eutherian mammals, X
chromosome inactivation (XCI) is required to ensure an equal transcriptional
level of most X-linked genes for both male and female embryos in adult tissues,
but this process is markedly different in cattle than mice. We examined how
sexual dimorphism affected conceptus transcript abundance and amino acid
composition as well as the endometrial transcriptome during the peri-implantation
period of pregnancy. Of the 5132 genes that were differentially expressed on Day
19 in male compared to female conceptuses, 2.7% were located on the X chromosome.
Concentrations of specific amino acids were higher in the uterine luminal fluid
of male compared to female conceptuses, while female conceptuses had higher
transcript abundance of specific amino acid transporters (SLC6A19 and SLC1A35).
Of note, the endometrial transcriptome was not different in cattle gestating a
male or a female conceptus. These data support the hypothesis that, far from
being a blastocyst-specific phenomenon, XCI is incomplete before and during
implantation in cattle. Despite differences in transcript abundance and amino
acid utilization in male versus female conceptuses, the sex of the conceptus
itself does not elicit a different transcriptomic response in the endometrium.
PMID- 27488035
TI - Hearing impairment and contributing factors among fertilizer factory workers.
AB - INTRODUCTION: Hearing impairment remains the main occupational health problem in
the manufacturing industry, and its contributing factors have not been well
controlled. METHODS: Unmatched case control and comparative studies were carried
out among fertilizer factory workers in Sarawak with the aim of determining
contributing factors for hearing impairment. Respondents consisted of 49 cases
that were diagnosed from 2005 to 2008 with 98 controls from the same work places.
Chi-square test and Mann-Whitney test were used in a univariate analysis to
determine the association between hearing impairment and the contributing risks
being studied. RESULTS: The results of the univariate analysis showed that
hearing impairment was significantly (p<0.05) associated with older age, lower
education level, high smoking dose, high occupational daily noise dose, longer
duration of service, infrequent used of hearing protection device (HPD), and low
perception of sound on HPD usage. Multivariate logistic regression of hearing
impairment after controlling for age found the following five variables:
occupational daily noise dose >=50% (OR 3.48, 95% CI 1.36-8.89), >=15 years of
services (OR 2.92, 95% CI 1.16-7.33), infrequent use of HPD (OR 2.79, 95% CI 1.15
6.77), low perception of sound on HPD (POR 2.77, 95% CI 1.09-6.97), and smoking
more than 20 packs per year (OR 4.71, 95% CI 1.13-19.68). DISCUSSION: In
conclusion, high occupational noise exposure level, longer duration of service,
low perception of sound on HPD, infrequent used of HPD, and smoking more than 20
packs per year were the contributing factors to hearing impairment, and
appropriate intervention measures should be proposed and taken into
considerations.
PMID- 27488034
TI - KLF10 Mediated Epigenetic Dysregulation of Epithelial CD40/CD154 Promotes
Endometriosis.
AB - Endometriosis is a highly prevalent, chronic, heterogeneous, fibro-inflammatory
disease that remains recalcitrant to conventional therapy. We previously showed
that loss of KLF11, a transcription factor implicated in uterine disease, results
in progression of endometriosis. Despite extensive homology, co-expression, and
human disease association, loss of the paralog Klf10 causes a unique
inflammatory, cystic endometriosis phenotype in contrast to fibrotic progression
seen with loss of Klf11. We identify here for the first time a novel role for
KLF10 in endometriosis. In an animal endometriosis model, unlike wild-type
controls, Klf10(-/-) animals developed cystic lesions with massive immune
infiltrate and minimal peri-lesional fibrosis. The Klf10(-/-) disease progression
phenotype also contrasted with prolific fibrosis and minimal immune cell
infiltration seen in Klf11(-/-) animals. We further found that lesion genotype
rather than that of the host determined each unique disease progression
phenotype. Mechanistically, KLF10 regulated CD40/CD154-mediated immune pathways.
Both inflammatory as well as fibrotic phenotypes are the commonest clinical
manifestations in chronic fibro-inflammatory diseases such as endometriosis. The
complementary, paralogous Klf10 and Klf11 models therefore offer novel insights
into the mechanisms of inflammation and fibrosis in a disease-relevant context.
Our data suggests that divergence in underlying gene dysregulation critically
determines disease-phenotype predominance rather than the conventional paradigm
of inflammation being precedent to fibrotic scarring. Heterogeneity in clinical
progression and treatment response are thus likely from disparate gene regulation
profiles. Characterization of disease phenotype-associated gene dysregulation
offers novel approaches for developing targeted, individualized therapy for
recurrent and recalcitrant chronic disease.
PMID- 27488036
TI - Hazard of ultraviolet radiation emitted in gas metal arc welding of mild steel.
AB - OBJECTIVES: Ultraviolet radiation (UVR) emitted during arc welding frequently
causes keratoconjunctivitis and erythema in the workplace. The degree of hazard
from UVR exposure depends on the welding method and conditions. Therefore, it is
important to identify the UVR levels present under various conditions. METHODS:
We experimentally evaluated the UVR levels emitted in gas metal arc welding
(GMAW) of mild steel. We used both a pulsed welding current and a non-pulsed
welding current. The shielding gases were 80% Ar + 20% CO2 and 100% CO2. The
effective irradiance defined in the American Conference of Governmental
Industrial Hygienists guidelines was used to quantify the UVR hazard. RESULTS:
The effective irradiance measured in this study was in the range of 0.51-12.9
mW/cm2 at a distance of 500 mm from the arc. The maximum allowable exposure times
at these levels are only 0.23-5.9 s/day. CONCLUSIONS: The following conclusions
were made regarding the degree of hazard from UVR exposure during the GMAW of
mild steel: (1) It is more hazardous at higher welding currents than at lower
welding currents. (2) At higher welding currents, it is more hazardous when 80%
Ar + 20% CO2 is used as a shielding gas than when 100% CO2 is used. (3) It is
more hazardous for pulsed welding currents than for non-pulsed welding currents.
(4) It appears to be very hazardous when metal transfer is the spray type. This
study demonstrates that unprotected exposure to UVR emitted by the GMAW of mild
steel is quite hazardous.
PMID- 27488037
TI - Efficacy of exercise therapy in workers with rotator cuff tendinopathy: a
systematic review.
AB - OBJECTIVE: To perform a systematic review of randomized controlled trials (RCTs)
on the efficacy of therapeutic exercises for workers suffering from rotator cuff
(RC) tendinopathy. METHODS: A literature search in four bibliographical databases
(Pubmed, CINAHL, EMBASE, and PEDro) was conducted from inception up to February
2015. RCTs were included if participants were workers suffering from RC
tendinopathy, the outcome measures included work-related outcomes, and at least
one of the interventions under study included exercises. The methodological
quality of the studies was evaluated with the Cochrane Risk of Bias Assessment
tool. RESULTS: The mean methodological score of the ten included studies was
54.4%+/-17.2%. Types of workers included were often not defined, and work-related
outcome measures were heterogeneous and often not validated. Three RCTs of
moderate methodological quality concluded that exercises were superior to a
placebo or no intervention in terms of function and return-to-work outcomes. No
significant difference was found between surgery and exercises based on the
results of two studies of low to moderate methodological quality. One study of
low methodological quality, comparing a workplace-based exercise program focusing
on the participants' work demands to an exercise program delivered in a clinical
setting, concluded that the work-based intervention was superior in terms of
function and return-to-work outcomes. CONCLUSION: There is low to moderate-grade
evidence that therapeutic exercises provided in a clinical setting are an
effective modality to treat workers suffering from RC tendinopathy and to promote
return-to-work. Further high quality studies comparing different rehabilitation
programs including exercises in different settings with defined workers
populations are needed to draw firm conclusions on the optimal program to treat
workers.
PMID- 27488038
TI - Influence of different safety shoes on gait and plantar pressure: a standardized
examination of workers in the automotive industry.
AB - OBJECTIVE: Working conditions, such as walking and standing on hard surfaces, can
increase the development of musculoskeletal complaints. At the interface between
flooring and musculoskeletal system, safety shoes may play an important role in
the well-being of employees. The aim of this study was to evaluate the effects of
different safety shoes on gait and plantar pressure distributions on industrial
flooring. METHODS: Twenty automotive workers were individually fitted out with
three different pairs of safety shoes ( "normal" shoes, cushioned shoes, and
midfoot bearing shoes). They walked at a given speed of 1.5 m/s. The CUELA
measuring system and shoe insoles were used for gait analysis and plantar
pressure measurements, respectively. Statistical analysis was conducted by ANOVA
analysis for repeated measures. RESULTS: Walking with cushioned safety shoes or a
midfoot bearing safety shoe led to a significant decrease of the average trunk
inclination (p<0.005). Furthermore, the average hip flexion angle decreased for
cushioned shoes as well as midfoot bearing shoes (p<0.002). The range of motion
of the knee joint increased for cushioned shoes. As expected, plantar pressure
distributions varied significantly between cushioned or midfoot bearing shoes and
shoes without ergonomic components. CONCLUSION: The overall function of safety
shoes is the avoidance of injury in case of an industrial accident, but in
addition, safety shoes could be a long-term preventive instrument for maintaining
health of the employees' musculoskeletal system, as they are able to affect gait
parameters. Further research needs to focus on safety shoes in working
situations.
PMID- 27488039
TI - Diagnosis accuracy of two vision screeners for visual health surveillance of
workers who use video display terminals.
AB - OBJECTIVE: To compare the diagnostic accuracy of two vision screeners by a visual
examination performed by an optometrist (gold standard) and to evaluate the
concordance between both screeners and between each screener and the gold
standard. METHODS: This was a cross-sectional study that included computer
workers who attended a routine yearly health examination. The study included
administrative office workers (n=91) aged 50.2+/-7.9 years (mean+/-standard
deviation), 69.2% of whom were women and 68.1% of whom used video display
terminals (VDT) for >4 h/day. The routine visual examination included monocular
and binocular distance visual acuity (VA), distance and near lateral phoria (LP),
stereo acuity (SA), and color vision. Tests were repeated with Optec 6500 (by
Stereo Optical) and Visiotest (by Essilor) screeners. Sensitivity, specificity,
positive predictive values (PPV), negative predictive values (NPV), and false
positive and negative rates were calculated. Kappa coefficient (kappa) was used
to measure the concordance of the screeners and the gold standard. RESULTS: The
sensitivity and specificity for monocular VA were over 80% for both vision
screeners; PPV was below 25%. Sensitivity and specificity were lower for SA (55%
70%), PPV was 50%, and NPV was 75% for both screeners. For distance LP,
sensitivity and PPV were <10% in both cases. The screeners differed in their
values for near LP: Optec 6500 had higher sensitivity (43.5%), PPV (37.0%), and
NPV (79.7%); whereas the Visiotest had higher specificity (83.8%). For color
vision, Visiotest showed low sensitivity, low PPV, and high specificity.
Visiotest obtained false positive rates that were lower or similar to Optec 6500,
and both screeners obtained false negative rates below 50%. Both screeners showed
poor concordance (kappa<0.40). CONCLUSIONS: A high value for NPV would qualify
both screeners as acceptable alternatives for visual health surveillance when
used as a screening tool; patients with positive test results should be referred
to a specialist.
PMID- 27488041
TI - The moderating role of overcommitment in the relationship between psychological
contract breach and employee mental health.
AB - OBJECTIVES: This study investigated whether the association between perceived
psychological contract breach (PCB) and employee mental health is moderated by
the cognitive-motivational pattern of overcommitment (OC). Linking the
psychological contract approach to the effort-reward imbalance model, this study
examines PCB as an imbalance in employment relationships that acts as a
psychosocial stressor in the work environment and is associated with stress
reactions that in turn negatively affect mental health. METHODS: The analyses
were based on a sample of 3,667 employees who participated in a longitudinal
linked employer-employee survey representative of large organizations (with at
least 500 employees who are subject so social security contributions) in Germany.
Fixed-effects regression models, including PCB and OC, were estimated for
employee mental health, and interaction effects between PCB and OC were assessed.
RESULTS: The multivariate fixed-effects regression analyses showed a significant
negative association between PCB and employee mental health. The results also
confirmed that OC does indeed significantly increase the negative effect of PCB
on mental health and that OC itself has a significant and negative effect on
mental health. CONCLUSIONS: The results suggest that employees characterized by
the cognitive-motivational pattern of OC are at an increased risk of developing
poor mental health if they experience PCB compared with employees who are not
overly committed to their work. The results of this study support the assumption
that psychosocial work stressors play an important role in employee mental
health.
PMID- 27488040
TI - Nickel-smelting fumes increased the expression of HIF-1alpha through PI3K/ERK
pathway in NIH/3T3 cells.
AB - OBJECTIVE: The purpose of this study was to investigate the effects of Nickel
(Ni) -smelting fumes on oncogenic proteins in vivo and in vitro. METHODS: Ni
fallout beside a Ni smelting furnace in a factory was sampled to study its toxic
effect. The effects of Ni-smelting fumes on the regulation of PI3K and ERK
signaling pathways and the important downstream hypoxia inducible factor, HIF
1alpha, were studied both in NIH/3T3 cells and in the lung tissue of rats.
NIH/3T3 cell transformation induced by Ni-smelting fumes was also observed.
RESULTS: Ni-smelting fumes activated PI3K, p-AKT, p70S6K1, and ERK proteins and
increased HIF-1alpha expression in a time- and dose-dependent manner. However,
activation was suppressed when NIH/3T3 cells were pretreated with PI3K/AKT or ERK
inhibitors. Ni-smelting fumes caused malignant transformation of NIH/3T3 cells.
CONCLUSIONS: Ni-smelting fumes increased the expression of HIF-1alpha through the
PI3K/ERK pathway in NIH/3T3 cells and induced malignant transformation in these
cells indicating that Ni-smelting fumes may be a potential carcinogen in
mammalian cells.
PMID- 27488043
TI - An advanced case of indium lung disease with progressive emphysema.
AB - OBJECTIVES: To report the occurrence of an advanced case of indium lung disease
with severely progressive emphysema in an indium-exposed worker. CASE REPORT: A
healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide
(ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an
epidemiological study was conducted on indium-exposed workers at the factory in
which he worked. The subject's serum indium concentration (In-S) was 99.7 MUg/l,
while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function
tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted
value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted),
and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography
(HRCT) scan showed mild interlobular septal thickening and mild emphysematous
changes. In 2008, he was transferred from the ITO grinding workplace to an
inspection work section, where indium concentrations in total dusts had a range
of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 MUg/l,
and pulmonary function tests revealed obstructive changes. In addition, HRCT scan
showed clear evidence of progressive lung destruction with accompanying severe
centrilobular emphysema and interlobular septal thickening in both lung fields.
The subject's condition gradually worsened, and in 2015, he was registered with
the Japan Organ Transplant Network for lung transplantation (LTx). CONCLUSIONS:
Heavy indium exposure is a risk factor for emphysema, which can lead to a
severity level that requires LTx as the final therapeutic option.
PMID- 27488042
TI - Dust-free bleaching powder may not prevent symptoms in hairdressers with
bleaching-associated rhinitis.
AB - OBJECTIVE: Hairdressers have an increased risk for airway symptoms especially
when using hair-bleaching powder containing persulfate. To minimize exposure,
dust-free bleaching powder (DFP) has been made available. We studied the effects
of regular powder (RP) or DFP on the airway symptoms of hairdressers with hair
bleaching associated rhinitis. METHODS: Twelve hairdressers each performed three
hair-bleachings on a wig in an exposure chamber. Half of the subjects used RP and
half used DFP. Exposure to persulfate and ammonia was measured. Before and after
each bleaching, the participants stated their degree of airway symptoms on a
visual analogue scale. Nasal lavage and blood were sampled before exposure, after
the last bleaching, and in the morning after exposure to measure inflammatory
markers. RESULTS: Exposure to persulfate was higher when using RP compared to
DFP, 22 (11-55) vs. 12 (8-13) MUg/m3; median (min-max). Exposure to ammonia did
not differ between the groups. Both groups reported an increase in asthma-like
symptoms and this increase was significant. Neutrophils, lymphocytes, and
monocytes increased after exposure in both groups; monocytes decreased the day
after. In nasal lavage, IL-8 was increased the morning after for both types of
powder, and the increase was significant in the total group. IL-6 increased
immediately after exposure and the day after only in the group using RP.
CONCLUSIONS: Although DFP powder emits lower levels of persulfate, effects are
still elicited in symptomatic hairdressers.
PMID- 27488044
TI - Investigation of rare chronic lipoid pneumonia associated with occupational
exposure to paraffin aerosol.
AB - OBJECTIVES: Occupational exposure to paraffin is an infrequent cause of lipoid
pneumonia (LP) and related data are scare. We investigated the possible
relationship between three rare cases of chronic LP and occupational exposure to
paraffin aerosol in an iron foundry. METHODS: The three cases of LP and their
workplaces were investigated using data from field investigations, air
monitoring, pulmonary radiological examinations, cell staining, and lung
biopsies. RESULTS: The patients had long-term occupational exposure to paraffin.
X-ray diffraction testing revealed that the raw material from the workshop was
paraffin crystal. The air concentrations of paraffin aerosol in workplaces were
significantly higher than outdoor background levels. Small diffuse and miliary
shadows with unclear edges were observed throughout the whole lungs via
radiography. Computed tomography revealed diffuse punctate nodules and a high
density of stripe-like shadows in both lungs (ground-glass opacity in a lower
lobe, and a mass-like lesion and high translucent area near the bottom of the
lung). Lipid-laden macrophages were found in the sputum and bronchial lavage. A
broadened alveolar septum and local focal fibrosis were also discovered via lung
biopsy. The inflammatory reaction in the lung tissues appeared to resolve over
time. CONCLUSIONS: These three rare cases of chronic LP in workers during molding
and repair processes were associated with occupational paraffin aerosol exposure.
Therefore, primary prevention is essential for molding or repairing workers in
the iron foundry, and a differential diagnosis of occupational chronic LP (vs.
pneumoconiosis) should be considered when treating these workers.
PMID- 27488045
TI - Buffering effect of workplace social capital on the association of job insecurity
with psychological distress in Japanese employees: a cross-sectional study.
AB - OBJECTIVES: The present study aimed to examine the buffering effect of workplace
social capital (WSC) on the association of job insecurity with psychological
distress in Japanese employees. METHODS: 2,971 employees from two factories of a
manufacturing company in Japan completed a self-administered questionnaire
including the scales on job insecurity, WSC, psychological distress, demographic
and occupational characteristics, and quantitative workload. Using psychological
distress (defined as a total score of the K6 scale >=5) as a dependent variable,
multiple logistic regression analyses were conducted. In a series of analyses,
interaction term of job insecurity*WSC was included in the model. RESULTS: After
adjusting for demographic and occupational characteristics as well as for
quantitative workload and interaction effect of quantitative workload*WSC, high
job insecurity and low WSC were significantly associated with psychological
distress. Furthermore, a significant interaction effect of job insecurity*WSC was
observed. Specifically, the association of job insecurity with psychological
distress was greater among those who perceived lower levels of WSC (prevalence
odds ratio=3.79 [95% confidence interval=2.70-5.32] for high vs. low job
insecurity subgroup) than among those who perceived higher levels of WSC
(prevalence odds ratio=2.96 [95% confidence interval=2.19-4.01] for high vs. low
job insecurity subgroup). These findings were replicated among permanent male
employees in the gender-stratified analyses. CONCLUSIONS: The present study
suggests that WSC has a buffering effect on the association of job insecurity
with psychological distress at least among Japanese permanent male employees.
PMID- 27488046
TI - Connexins in endothelial barrier function - novel therapeutic targets countering
vascular hyperpermeability.
AB - Prolonged vascular hyperpermeability is a common feature of many diseases.
Vascular hyperpermeability is typically associated with changes in the expression
patterns of adherens and tight junction proteins. Here, we focus on the less
appreciated contribution of gap junction proteins (connexins) to basal vascular
permeability and endothelial dysfunction. First, we assess the association of
connexins with endothelial barrier integrity by introducing tools used in
connexin biology and relating the findings to customary readouts in vascular
biology. Second, we explore potential mechanistic ties between connexins and
junction regulation. Third, we review the role of connexins in microvascular
organisation and development, focusing on interactions of the endothelium with
mural cells and tissue-specific perivascular cells. Last, we see how connexins
contribute to the interactions between the endothelium and components of the
immune system, by using neutrophils as an example. Mounting evidence of crosstalk
between connexins and other junction proteins suggests that we rethink the way in
which different junction components contribute to endothelial barrier function.
Given the multiple points of connexin-mediated communication arising from the
endothelium, there is great potential for synergism between connexin-targeted
inhibitors and existing immune-targeted therapeutics. As more drugs targeting
connexins progress through clinical trials, it is hoped that some might prove
effective at countering vascular hyperpermeability.
PMID- 27488047
TI - "It's my business, it's my body, it's my money": experiences of smokers who are
not planning to quit in the next 30 days and their views about treatment options.
AB - BACKGROUND: Current evidence-based smoking cessation treatments in the UK are
only offered to smokers ready to quit within 30 days. This study reports the
experiences of smokers who are not ready to quit and explores the types of
intervention approaches that might engage them. METHODS: Five focus groups were
conducted with smokers who had no plans to quit within 30 days (n = 32, 44 %
female). Verbatim transcripts were analyzed thematically using Nvivo 10 software.
RESULTS: Participants were ambivalent towards their own smoking, but the majority
indicated they would like to quit someday. Smoking was seen both to hinder and
facilitate social interactions, depending on the social norms of the
participant's social circle. Participants reported that, when they perceive
pressure to quit smoking, they respond defensively; concurrently, existing
approaches to encouraging smoking cessation were seen as unappealing. In
contrast, the importance of intrinsic motivation to quit was emphasized, and
interventions that were tailored, increased intrinsic motivation and kept the
smoker engaged in activities incompatible with smoking were preferred.
CONCLUSIONS: Despite not planning to quit in the next 30 days, the majority of
participants wanted to quit smoking at some point. Even if existing services were
offered to smokers not planning to quit in the next 30 days, it is unlikely that
these services would meet the needs of this population. Future research should
explore novel approaches to appeal specifically to smokers not planning to quit
in the next 30 days, such as encouraging engagement with activities incompatible
with smoking and fostering non-smoking habits.
PMID- 27488049
TI - Oral bioavailability enhancement through supersaturation: an update and meta
analysis.
AB - INTRODUCTION: With the increasing number of poorly water-soluble compounds in
drug discovery pipelines, supersaturating drug delivery systems (SDDS) have
attracted increased attention as an effective bioavailability enhancing approach.
However, a systematic and quantitative synopsis of the knowledge about
performance of SDDS is currently lacking. Such analysis of the recent
achievements is to provide insights for formulation scientists dealing with
poorly soluble compounds. Areas covered: A systematic search of two evidence
based International databases, Medline and Embase, from 2010 to Dec 2015, has
been performed. By conducting meta-analysis, box-plots, and correlation plots of
the relevant data retrieved from literature, the current review addresses three
quantitative questions: (1) how promising are SDDS for bioavailability
enhancement? (2) which types of SDDS perform best? and (3) what are the most
promising drug candidates? Four widely reported types of SDDS were compared:
amorphous solid dispersions, nano-drug systems, supersaturable lipid-based
formulations, and silica-based systems. Expert opinion: While SDDS formulations
appear to be a promising candidate-enabling technique for drug development, the
prediction of their in vivo performance by in vitro testing remains challenging.
A transition from a trial-and-error development approach towards an approach
guided by mechanistic insight, as well as the development of more efficient
predictive tools for performance ranking is urgently needed.
PMID- 27488048
TI - Exposure to various abscission-promoting treatments suggests substantial ERF
subfamily transcription factors involvement in the regulation of cassava leaf
abscission.
AB - BACKGROUND: Cassava plants (Manihot esculenta Crantz) have obvious abscission
zone (AZ) structures in their leaf pulvinus-petioles. Cassava leaf abscission can
be triggered by either 17 days of water-deficit stress or 4 days of ethylene
treatment. To date, little is known about cassava AP2/ERF factors, and less is
known regarding their roles in regulating abscission zone development. RESULTS:
Here, the cassava and Arabidopsis AP2/ERF genes were compared, finding that the
cassava genome contains approximately 1.54-fold more ERF subfamily than the
Arabidopsis genome. Microarray analysis was used to identify the AP2/ERF genes
that are expressed in cassava leaf pulvinus-petiole abscission zones by comparing
the AP2/ERF gene expression profiles of ethylene- and water-deficit stress
induced leaf abscission. In total, 99 AP2/ERF genes were identified as expressed
in AZs across six time points during both ethylene- and water-deficit stress
induced leaf abscission. Comparative expression profile analysis of similar SOTA
(Self Organizing Tree Algorithm) clusters at six time points during ethylene- and
water-deficit stress-induced leaf abscission demonstrated that 20 ERF subfamily
genes had similar expression patterns in response to both treatments. GO (Gene
Ontology) annotation confirmed that all 20 ERF subfamily genes participate in
ethylene-mediated signalling. Analysis of the putative ERF promoter regions shown
that the genes contained primarily ethylene- and stress-related cis-elements.
Further analysis of ACC oxidase activity in AZs across six time points during
abscission shown increased ethylene production in response to both ethylene and
water-deficit stress; however, the difference was more dramatic for water-deficit
stress. Finally, the expression ratios of 20 ERF subfamily genes were analysed in
two cassava cultivars, 'KU50' and 'SC5', that exhibit different levels of leaf
abscission when challenged with the same water-deficit stress. The analysis
indicated that most of the ERF genes were expressed at higher levels in the
precocious abscission 'KU50' cultivar than in the delayed abscission 'SC5'
cultivar. CONCLUSION: Ccomparative analysis of both ethylene- and water-deficit
stress-induced leaf abscission shown that the ERF subfamily functions in the
regulation of cassava abscission zone development.
PMID- 27488052
TI - Application of proteomics in research on traditional Chinese medicine.
AB - INTRODUCTION: Traditional Chinese medicine (TCM) is a widely used complementary
alternative medicine approach. Although many aspects of its effectiveness have
been approved clinically, rigorous scientific techniques are highly required to
translate the promises from TCM into powerful modern therapies. In this respect,
proteomics is useful because of its ability to unveil the underlying target
proteins and/or protein biomarkers. AREAS COVERED: In this review, we summarize
the recent interplay between proteomics and research on TCM, ranging from
exploration of the medicinal materials to the biological basis of TCM concepts,
and from pathological studies to pharmacological investigations. We show that
proteomic analyses provide preliminary biological evidence of the promises in
TCM, and the integration of proteomics with other omics and bioinformatics offers
a comprehensive methodology to address the complications of TCM. Expert
commentary: Currently, only limited information can be obtained regarding TCM
issues and thus more work is required to resolve the ambiguity. As such, more
collaborations between proteomics and other techniques (other omics, network
pharmacology, etc.) are essential for deciphering the underlying biological basis
in TCM topics.
PMID- 27488051
TI - Treatment with L-citrulline and metformin in Duchenne muscular dystrophy: study
protocol for a single-centre, randomised, placebo-controlled trial.
AB - BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease
that affects 1 in 3500-6000 male births. Despite broad research aiming to improve
muscle function as well as heart and brain function, sufficient therapeutic
efficacy has not yet been achieved and current therapeutic management is still
supportive. In a recent pilot trial, oral treatment with L-arginine and metformin
showed consistent changes of muscular metabolism both in vitro and in vivo by
raising NO levels and expression of mitochondrial proteins in the skeletal muscle
tissue of patients with DMD. This randomised, double-blind, placebo-controlled
trial aims to demonstrate the superiority of L-citrulline and metformin therapy
over placebo in DMD patients with regard to the Motor Function Measure (MFM) D1
subscore (primary endpoint) as well as additional clinical and subclinical tests.
METHODS/DESIGN: A total of 40-50 ambulant patients with DMD will be recruited at
the outpatient department of the University of Basel Children's Hospital
(Switzerland), as well as from the DMD patient registries of Switzerland, Germany
and Austria. Patients will be randomly allocated to one of the two arms of the
study and will receive either a combination of L-citrulline and metformin or
placebo for 26 weeks. Co-medication with glucocorticoids is allowed. The primary
endpoint is the change of the MFM D1 subscore from baseline to week 26 under L
citrulline and metformin therapy. Secondary endpoints will include the motor
function measure (MFM) and its items and subscores, the 6-minute walking test,
timed function tests and quantitative muscle testing. Furthermore, quantitative
muscle MRI assessment to evaluate the muscle fat fraction as well as safety and
biomarker laboratory analyses from blood will be included. For comparison, muscle
metabolism and mitochondrial function will be analysed in 10-20 healthy age
matched male children. DISCUSSION: The aim of this study is to test if a 6-month
treatment of a combination of L-citrulline and metformin is more effective than
placebo in preventing loss of motor function and muscle degeneration in DMD. The
MFM D1 subscore is used as a clinical outcome measure and a quantitative muscle
MRI assessment as the surrogate outcome measure of fatty muscle degeneration.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT01995032 . Registered on 20 November
2013.
PMID- 27488053
TI - Elucidating diversity of exosomes: biophysical and molecular characterization
methods.
AB - Exosomes are cell-secreted nanovesicles present in biological fluids in normal
and diseased conditions. Owing to their seminal role in cell-cell communication,
emerging evidences suggest that exosomes are fundamental regulators of various
diseases. Due to their potential usefulness in disease diagnosis, robust
isolation and characterization of exosomes is critical in developing exosome
based assays. In the last few years, different exosome characterization methods,
both biophysical and molecular, have been developed to characterize these tiny
vesicles. Here, in this review we summarize: first, biophysical techniques based
on spectroscopy (e.g., Raman spectroscopy, dynamic light scattering) and other
principles, for example, scanning electron microscopy, atomic force microscopy;
second, antibody-based molecular techniques including flow cytometry,
transmission electron microscopy and third, nanotechnology-dependent exosome
characterization methodologies.
PMID- 27488055
TI - Commentary: Rapid Phosphoproteomic Effects of Abscisic Acid (ABA) on Wild-Type
and ABA Receptor-Deficient A. thaliana Mutants.
PMID- 27488056
TI - Erratum to: Fertility rates among very young adolescent women: temporal and
spatial trends in Brazil.
PMID- 27488054
TI - Phytochemical, antioxidant and hepatoprotective effects of Alnus nitida bark in
carbon tetrachloride challenged Sprague Dawley rats.
AB - BACKGROUND: Alnus nitida (Spach) Endl. is traditionally used for inflammatory
disorders. Diarylheptanoids constituents having diverse therapeutically
importance including hepato-protective was reported in A. nitida. The aim of this
study was to explore the antioxidant and hepato-protective profile of A. nitida
stem bark's crude methanol extract (ANM). METHODS: Crude methanol extract of A.
nitida stem bark and its derived fractions were assessed for phytochemical
classes and in vitro antioxidant profiling by multidimensional assays. Hepato
protective assessment of ANM was investigated on rats, which were made
hepatotoxic using carbon tetrachloride (CCl4). Additionally HPLC-DAD analysis of
ANM, and its derived ethyl acetate and aqueous fraction was carried out to
determine the presence of active constituents. RESULTS: Qualitative analysis of
crude extract-and its fractions depicted the presence of terpenoids, saponins,
coumarins, phenols and flavonoids. Maximum quantity of total phenolic content
(TPC) and total flavonoid content (TFC) was recorded in ANM and its derived
fractions; n-hexane (ANH), chloroform (ANC), ethyl acetate (ANE) and the residual
aqueous (ANA). ANM exhibited the best total antioxidant capacity, total reducing
power, and scavenging of DPPH and OH radicals. ANE and ANA exhibited strong
scavenging potential for iron chelation, nitric oxide and beta-carotene bleaching
assay. ANM treatment converse the activities of serum-marker enzymes and lipid
profile, altered by CCl4 treatment in rat. CCl4 induced hepatic-cirrhosis in rat
resulted in decrease of antioxidant enzyme activities such as catalase,
peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S
transferase and glutathione reductase-which were restored towards the normal
level with ANM. Similarly diminished level of reduced glutathione while enhanced
level of lipid peroxides, hydrogen peroxide and nitrite in liver of cirrhotic
rats was normalized by treatment of ANM. The histopathological studies of liver
tissues also represented that ANM possessed the hepato-protective activity. HPLC
DAD analysis against eight known standards confirmed the presence of gallic acid,
catechin and rutin in ANM and in ANA while in ANE gallic acid was only detected.
CONCLUSION: Based on the results of antioxidants, restoration of various
antioxidant enzymes and histopathological studies, the recent study concludes
that antioxidant potential of A. nitida bark might protect the liver damages.
PMID- 27488057
TI - Developmental outcomes and physical activity behaviour in children post major
surgery: an observational study.
AB - BACKGROUND: Infants may be at neurodevelopmental risk from adverse events arising
in the neonatal period. This study aimed to investigate the developmental
outcomes and physical activity behaviours of term infants after neonatal major
surgery, at age three years. METHODS: This prospective study enrolled infants who
underwent major surgery in their first 90 days, between August 2006 and December
2008. Developmental status was assessed using the Bayley Scales of Infant and
Toddler Development, Third Edition (BSID-III). Physical activity and sedentary
behaviour (i.e. small screen recreation) (SSR) were assessed using the Preschool
Age Physical Activity Questionnaire (Pre-PAQ). Activity (moving between slow to
fast pace) and SSR were reported for a 3-day period. RESULTS: One hundred and
thirty five children (68 major surgery, 67 control) were assessed, using both
measures, at age three years. Both groups were within the average range across
all domains of the BSID-III although the surgical group was significantly below
the controls for cognition (t = -3.162, p = 0.002) receptive language (t =
3.790, p < 0.001) and fine motor skills (t = -2.153, p = 0.03). Mean activity
time for the surgical group was 191 mins.day(-1), and 185 mins.day-1 for
controls. Mean SSR time was 77 mins.day(-1), and 83 mins.day(-1) for the
respective groups. There was no significant difference between groups for either
physical activity (p = 0.71) or SSR time (p = 0.49). CONCLUSIONS: By age three,
children who had major surgery in infancy are developmentally normal but have not
quite caught up with their peer group in cognitive, receptive language and fine
motor skill domains. Both groups met recommended 3 h of daily physical activity
but exceeded 60-min SSR time recommended for preschool-age children.
PMID- 27488059
TI - Carryover Effects in Sibling Comparison Designs.
AB - A convenient way of dealing with confounding is the sibling comparison design,
where the outcome in exposed individuals is compared with the outcome in their
unexposed siblings. The standard analysis of sibling comparison designs assumes
that the exposure and outcome of an individual do not affect the exposure and
outcome of his/her siblings, sometimes referred to as an absence of sibling
carryover or contagion effects. Unfortunately, there are many situations where
carryover effects are likely to be present. In this article, we explore the
consequences of carryover effects for sibling comparison designs. We show, using
causal diagrams, when and why carryover effects lead to bias, and we investigate
the sign and magnitude of this bias under various scenarios.
PMID- 27488060
TI - Commentary: Integrating Complex Systems Thinking into Epidemiologic Research.
PMID- 27488058
TI - Nox2-Mediated PI3K and Cofilin Activation Confers Alternate Redox Control of
Macrophage Pinocytosis.
AB - AIMS: Internalization of extracellular fluid and its solute by macropinocytosis
requires dynamic reorganization of actin cytoskeleton, membrane ruffling, and
formation of large endocytic vacuolar compartments, called macropinosomes, inside
the cell. Although instigators of macropinocytosis, such as growth factors and
phorbol esters, stimulate NADPH oxidase (Nox) activation and signal transduction
mediators upstream of Nox assembly, including Rac1 and protein kinase C (PKC),
are involved in macropinocytosis, the role of Nox enzymes in macropinocytosis has
never been investigated. This study was designed to examine the role of Nox2 and
the potential downstream redox signaling involved in macropinocytosis. RESULTS:
Phorbol myristate acetate activation of human and murine macrophages stimulated
membrane ruffling, macropinosome formation, and subsequent uptake of
macromolecules by macropinocytosis. Mechanistically, we found that
pharmacological blockade of PKC, transcriptional knockdown of Nox2, and
scavenging of intracellular superoxide anion abolished phorbol ester-induced
macropinocytosis. We observed that Nox2-derived reactive oxygen species via
inhibition of phosphatase and tensin homolog and activation of the
phosphoinositide-3-kinase (PI3K)/Akt pathway lead to activation of actin-binding
protein cofilin, membrane ruffling, and macropinocytosis. Similarly, activation
of macropinocytosis by macrophage colony-stimulating factor involves Nox2
mediated cofilin activation. Furthermore, peritoneal chimera experiments indicate
that macropinocytotic uptake of lipids in hypercholesterolemic ApoE-/- mice was
attenuated in Nox2y/- macrophages compared with wild-type controls. Innovation
and Conclusion: In summary, these findings demonstrate a novel Nox2-mediated
mechanism of solute uptake via macropinocytosis, with broad implications for both
general cellular physiology and pathological processes. The redox mechanism
described here may also identify new targets in atherosclerosis and other disease
conditions involving macropinocytosis. Antioxid. Redox Signal. 26, 902-916.
PMID- 27488061
TI - Giant sinus of Valsalva aneurysm.
PMID- 27488062
TI - Molecular Genomics of Eye Diseases.
PMID- 27488063
TI - Ocular Gene Therapy-The Future Is Now.
PMID- 27488064
TI - Age-Related Macular Degeneration: Genetics and Biology.
AB - Age-related macular degeneration (AMD), widely prevalent across the globe, is a
major stakeholder among adult visual morbidity and blindness, not only in the
Western world but also in Asia. Several risk factors have been identified,
including critical genetic factors, which were never imagined 2 decades ago. The
etiopathogenesis is emerging to demonstrate that immune and complement-related
inflammation pathway members chronically exposed to environmental insults could
justifiably influence disease morbidity and treatment outcomes. Approximately
half a dozen physiological and biochemical cascades are disrupted in the AMD
disease genesis, eventually leading to the distortion and disruption of the
subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting
off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen
genetic factors have so far been identified, including the recent ones, through
powerful genomic technologies and large robust sample sizes. The noteworthy
genetic variants (common and rare) are complement factor H, complement factor H
related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A,
vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal
link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous
amount of scientific information generated over the years, diagnostic genetic or
biomarker tests are still not available for clinicians to understand the natural
course of the disease and its management in a patient. However, further research
in the field should reduce this gap not only by aiding the clinician but also
through the possibilities of clinical intervention with complement pathway
related inhibitors entering preclinical and clinical trials in the near future.
PMID- 27488065
TI - Myopia Genetics-The Asia-Pacific Perspective.
AB - Myopia is a major cause of visual impairment worldwide. In particular, high
myopia is associated with serious blinding complications, including retinal
detachment, chorioretinal degeneration, and choroidal neovascularization. Myopia
is multifactorial in etiology, resulting from the interaction of environmental
and genetic risk factors. During the past 2 decades, a large number of gene loci
and variants have been identified for myopia. There are more than 20 myopia
associated loci spanning all chromosomes. Earlier findings were obtained mainly
from family linkage analyses and candidate gene studies, and more recent results
are principally from genome-wide association studies and exome sequencing. Some
genetic associations have been successfully validated and replicated in
populations of different geographic localities and ethnicities, but some have
not. Compared with Whites, Asian populations-in particular Japanese, Korean, and
Chinese-have a much higher prevalence of myopia, especially high myopia. Both
genetic and environmental factors contribute to such ethnic variations. This
review attempts to summarize and compare the allelic frequencies of gene variants
known to be associated with myopia in different ethnic groups, especially in the
Asia-Pacific region.
PMID- 27488066
TI - Gene-Based Therapies for Leber Hereditary Optic Neuropathy. Hype or Hope?
AB - Leber hereditary optic neuropathy has now joined Leber congenital amaurosis in
the list of genetic eye diseases undergoing gene therapy clinical trials.
Although a dramatic response to treatment would be welcome, a minor improvement
in vision is a major challenge in efficacy assessment, given this may occur
spontaneously as part of the natural history of minor recovery in some patients.
Thus, we must await the outcome of adequately powered clinical trials to know if
the treatment is effective, particularly given the likely high cost of such
therapeutic interventions in the future. We need global cooperation to ensure
that the most suitable patients are enrolled in these trials and that support is
provided for participants who need to travel from the Asia-Pacific region to
Europe or North America if there are no local arms of these trials.
PMID- 27488067
TI - Glaucoma Genetics: Recent Advances and Future Directions.
AB - Once considered primarily a disease of aging caused by unknown environmental
influences, the notion that heritable factors could significantly contribute to
the pathogenesis of sporadic glaucoma has rapidly gained traction. In part, this
is due to the rapid and definitive identification of genes with strong effects on
familial, earlier onset forms of glaucoma. Although the endpoint of glaucoma is
irreversible optic nerve damage accompanied by blindness, the initial inciting
trigger could differ. To this end, well-powered genome-wide association studies
have each been conducted for primary open-angle glaucoma, primary angle-closure
glaucoma, along with exfoliation syndrome and glaucoma. Each of these studies has
revealed sets of significantly associated genetic loci implicating biological
pathways that do not overlap between the forms of glaucoma. Although substantial
biological insight has been gained from their identification, much further work
remains to definitively link the implicated genetic variants with glaucoma
causation. It is also hoped that the genetic findings could point us to potential
routes of therapy beyond that of intraocular pressure-lowering medications or
surgery.
PMID- 27488068
TI - Genetics of Retinoblastoma.
AB - Retinoblastoma is a malignant retinal tumor that affects young children.
Mutations in the RB1 gene cause retinoblastoma. Mutations in both RB1 alleles
within the precursor retinal cell are essential, with one mutation that may be
germline or somatic and the second one that is always somatic. Identification of
the RB1 germline status of a patient allows differentiation between sporadic and
heritable retinoblastoma variants. Application of this knowledge is crucial for
assessing short-term (risk of additional tumors in the same eye and other eye)
and long-term (risk of nonocular malignant tumors) prognosis and offering cost
effective surveillance strategies. Genetic testing and genetic counseling are
therefore essential components of care for all children diagnosed with
retinoblastoma. The American Joint Committee on Cancer has acknowledged the
importance of detecting this heritable trait and has introduced the letter "H" to
denote a heritable trait of all cancers, starting with retinoblastoma (in
publication). In this article, we discuss the clinically relevant aspects of
genetic testing and genetic counseling for a child with retinoblastoma.
PMID- 27488069
TI - Retinitis Pigmentosa: Progress and Perspective.
AB - Retinitis pigmentosa is the most common form of hereditary retinal degeneration
causing blindness. Great progress has been made in the identification of the
causative genes. Gene diagnosis will soon become an affordable routine clinical
test because of the wide application of next-generation sequencing. Gene-based
therapy provides hope for curing the disease. Investigation into the molecular
pathways from mutation to rod cell death may reveal targets for developing new
treatment. Related progress with existing systematic review is briefly summarized
so that readers may find the relevant references for in-depth reading. Future
trends in the study of retinitis pigmentosa are also discussed.
PMID- 27488070
TI - Strategies for Gene Mapping in Inherited Ophthalmic Diseases.
AB - Gene mapping of inherited ophthalmic diseases such as congenital cataracts,
retinal degeneration, glaucoma, age-related macular degeneration, myopia, optic
atrophy, and eye malformations has shed more light on the disease pathology,
identified targets for research on therapeutics, earlier detection, and treatment
options for disease management and patient care. This article details the
different approaches to gene identification for both Mendelian and complex eye
disorders.
PMID- 27488071
TI - Gene Therapy for Age-Related Macular Degeneration.
AB - The purpose of this article was to evaluate safety and signals of efficacy of
gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration
(wet AMD). A phase 1 dose-escalating single-center controlled unmasked human
clinical trial was followed up by extension of the protocol to a phase 2A single
center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti
vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In
phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 * 10 vector
genomes) and 1 subject to the control arm; step 2 randomized an additional 3
subjects to treatment with high-dose rAAV.sFlt-1 (1 * 10 vector genomes) and 1
subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was
well tolerated with a favorable safety profile in these elderly subjects with wet
AMD. Subretinal injection was highly reproducible, and no drug-related adverse
events were reported. Procedure-related adverse events were mild and self
resolving. Two phakic patients developed cataract and underwent cataract surgery.
Four of the 6 patients responded better than the small control group in this
study and historical controls in terms of maintaining vision and a relatively dry
retina with zero ranibizumab retreatments per annum. Two patients required 1
ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy
may prove to be a potential adjunct or alternative to conventional intravitreal
injection for patients with wet AMD by providing extended delivery of a naturally
occurring antiangiogenic protein.
PMID- 27488072
TI - Clustered Regularly Interspaced Short Palindromic Repeats: Challenges in Treating
Retinal Disease.
AB - Ophthalmic researchers and clinicians arguably have led the way for safe,
effective gene therapy, most notably with adeno-associated viral gene
supplementation in the treatment for patients with Leber congenital amaurosis
type 2 with mutations in the RPE65 gene. These successes notwithstanding, most
other genetic retinal disease will be refractory to supplementation. The ideal
gene therapy approach would correct gene mutations to restore normal function in
the affected cells. Gene editing in which a mutant allele is inactivated or
converted to sequence that restores normal function is hypothetically one such
approach. Such editing involves site-specific digestion of mutant genomic DNA
followed by repair. Previous experimental approaches were hampered by inaccurate
and high rates of off-site lesioning and by overall low digestion rates. A new
tool, clustered regularly interspaced short palindromic repeats coupled with the
nuclease Cas9, may address both shortcomings. Some of the many challenges that
must be addressed in moving clustered regularly interspaced short palindromic
repeats coupled with the nuclease Cas9 therapies to the ophthalmic clinic are
discussed here.
PMID- 27488073
TI - Exercise as Gene Therapy: BDNF and DNA Damage Repair.
AB - DNA damage is a common feature of neurodegenerative illnesses, and the ability to
repair DNA strand breaks and lesions is crucial for neuronal survival, reported
by Jeppesen et al (Prog Neurobiol. 2011;94:166-200) and Shiwaku et al (Curr Mol
Med. 2015;15:119-128). Interventions aimed at repairing these lesions, therefore,
could be useful for preventing or delaying the progression of disease. One
potential strategy for promoting DNA damage repair (DDR) is exercise. Although
the role of exercise in DDR is not understood, there is increasing evidence that
simple physical activity may impact clinical outcomes for neurodegeneration.
Here, we discuss what is currently known about the molecular mechanisms of brain
derived neurotrophic factor and how these mechanisms might influence the DDR
process.
PMID- 27488074
TI - Gene Therapy and Gene Editing for the Corneal Dystrophies.
AB - Despite ever-increasing understanding of the genetic underpinnings of many
corneal dystrophies, gene therapy designed to ameliorate disease has not yet been
reported in any human patient. In this review, we explore the likely reasons for
this apparent failure of translation. We identify the requirements for success:
the genetic defect involved must have been identified and mapped, vision in the
affected patient must be significantly impaired or likely to be impaired, no
better or equivalently effective treatment must be available, the treatment must
be capable of modulating corneal pathology, and delivery of the construct to the
appropriate cell must be practicable. We consider which of the corneal
dystrophies might be amenable to treatment by genetic manipulations, summarize
existing therapeutic options for treatment, and explore gene editing using
clustered regularly interspaced short palindromic repeat/Cas and other similar
transformative technologies as the way of the future. We then summarize recent
laboratory-based advances in gene delivery and the development of in vitro and in
vivo models of the corneal dystrophies. Finally, we review recent experimental
work that has increased our knowledge of the pathobiology of these conditions.
PMID- 27488075
TI - Enhanced hydrogenation activity and diastereomeric interactions of methyl
pyruvate co-adsorbed with R-1-(1-naphthyl)ethylamine on Pd(111).
AB - Unmodified racemic sites on heterogeneous chiral catalysts reduce their overall
enantioselectivity, but this effect is mitigated in the Orito reaction (methyl
pyruvate (MP) hydrogenation to methyl lactate) by an increased hydrogenation
reactivity. Here, this effect is explored on a R-1-(1-naphthyl)ethylamine (NEA)
modified Pd(111) model catalyst where temperature-programmed desorption
experiments reveal that NEA accelerates the rates of both MP hydrogenation and
H/D exchange. NEA+MP docking complexes are imaged using scanning tunnelling
microscopy supplemented by density functional theory calculations to allow the
most stable docking complexes to be identified. The results show that
diastereomeric interactions between NEA and MP occur predominantly by binding of
the C=C of the enol tautomer of MP to the surface, while simultaneously
optimizing C=O....H2N hydrogen-bonding interactions. The combination of chiral
NEA driven diastereomeric docking with a tautomeric preference enhances the
hydrogenation activity since C=C bonds hydrogenate more easily than C=O bonds
thus providing a rationale for the catalytic observations.
PMID- 27488076
TI - Child and youth experiences and perspectives of cerebral palsy: a qualitative
systematic review: letter to the editor.
PMID- 27488077
TI - Response to Boyd letter.
PMID- 27488079
TI - Time-dependent uptake and trafficking of vesicles capturing extracellular S100B
in cultured rat astrocytes.
AB - Astrocytes, the most heterogeneous glial cells in the central nervous system,
contribute to brain homeostasis, by regulating a myriad of functions, including
the clearance of extracellular debris. When cells are damaged, cytoplasmic
proteins may exit into the extracellular space. One such protein is S100B, which
may exert toxic effects on neighboring cells unless it is removed from the
extracellular space, but the mechanisms of this clearance are poorly understood.
By using time-lapse confocal microscopy and fluorescently labeled S100B (S100B
Alexa488 ) and fluorescent dextran (Dextran546 ), a fluid phase uptake marker, we
examined the uptake of fluorescently labeled S100B-Alexa488 from extracellular
space and monitored trafficking of vesicles that internalized S100B-Alexa488 .
Initially, S100B-Alexa488 and Dextran546 internalized with distinct rates into
different endocytotic vesicles; S100B-Alexa488 internalized into smaller vesicles
than Dextran546 . At a later stage, S100B-Alexa488 -positive vesicles
substantially co-localized with Dextran546 -positive endolysosomes and with
acidic LysoTracker-positive vesicles. Cell treatment with anti-receptor for
advanced glycation end products (RAGE) antibody, which binds to RAGE, a
'scavenger receptor', partially inhibited uptake of S100B-Alexa488 , but not of
Dextran546 . The dynamin inhibitor dynole 34-2 inhibited internalization of both
fluorescent probes. Directional mobility of S100B-Alexa488 -positive vesicles
increased over time and was inhibited by ATP stimulation, an agent that increases
cytosolic free calcium concentration ([Ca2+ ]i ). We conclude that astrocytes
exhibit RAGE- and dynamin-dependent vesicular mechanism to efficiently remove
S100B from the extracellular space. If a similar process occurs in vivo,
astroglia may mitigate the toxic effects of extracellular S100B by this process
under pathophysiologic conditions. This study reveals the vesicular clearance
mechanism of extracellular S100B in astrocytes. Initially, fluorescent S100B
internalizes into smaller endocytotic vesicles than dextran molecules. At a later
stage, both probes co-localize within endolysosomes. S100B internalization is
both dynamin- and RAGE-dependent, whereas dextran internalization is dependent on
dynamin. Vesicle internalization likely mitigates the toxic effects of
extracellular S100B and other waste products.
PMID- 27488080
TI - Validation of Random Sampling as an Estimation Procedure for Lyme Disease
Surveillance in Massachusetts and Minnesota.
AB - Many disease surveillance programs, including the Massachusetts Department of
Public Health and the Minnesota Department of Health, are challenged by marked
increases in Lyme disease (LD) reports. The purpose of this study was to
retrospectively analyse LD reports from 2005 through 2012 to determine whether
key epidemiologic characteristics were statistically indistinguishable when an
estimation procedure based on sampling was utilized. Estimates of the number of
LD cases were produced by taking random 20% and 50% samples of laboratory-only
reports, multiplying by 5 or 2, respectively, and adding the number of provider
reported confirmed cases. Estimated LD case counts were compared to observed,
confirmed cases each year. In addition, the proportions of cases that were male,
were <=12 years of age, had erythema migrans (EM), had any late manifestation of
LD, had a specific late manifestation of LD (arthritis, cranial neuritis or
carditis) or lived in a specific region were compared to the proportions of cases
identified using standard surveillance to determine whether estimated proportions
were representative of observed proportions. Results indicate that the estimated
counts of confirmed LD cases were consistently similar to observed, confirmed LD
cases and accurately conveyed temporal trends. Most of the key demographic and
disease manifestation characteristics were not significantly different (P <
0.05), although estimates for the 20% random sample demonstrated greater
deviation than the 50% random sample. Applying this estimation procedure in
endemic states could conserve limited resources by reducing follow-up effort
while maintaining the ability to track disease trends.
PMID- 27488081
TI - Minocycline combination therapy with fluvoxamine in moderate-to-severe obsessive
compulsive disorder: A placebo-controlled, double-blind, randomized trial.
AB - AIM: Several lines of evidence implicate glutamatergic dysfunction in the
pathophysiology of obsessive-compulsive disorder (OCD), presenting this
neurotransmitter as a target for the development of novel pharmacotherapy. The
objective of this study was to assess the efficacy of minocycline as an
augmentative agent to fluvoxamine in the treatment of patients with OCD. METHODS:
One hundred and two patients with the diagnosis of moderate-to-severe OCD were
recruited to this study. A randomized double-blind trial was designed and
patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10
weeks. The patients randomly received either minocycline 100 mg twice per day or
placebo for 10 weeks. All patients received fluvoxamine (100 mg/day) for the
first 4 weeks, followed by 200 mg/day for the rest of the trial, regardless of
their treatment groups. Participants were evaluated using the Yale-Brown
Obsessive Compulsive Scale (Y-BOCS). The main outcome measure was to assess the
efficacy of minocycline in improving the OCD symptoms. RESULTS: General linear
model repeated measures demonstrated significant effect for time * treatment
interaction on the Y-BOCS total scores, F(1.49, 137.93) = 7.1, P = 0.003, and Y
BOCS Obsession subscale score, F(1.54, 141.94) = 9.72, P = 0.001, and near
significant effect for the Y-BOCS Compulsion subscale score, F(1.27, 117.47) =
2.92, P = 0.08. A significantly greater rate of partial and complete response
was observed in the minocycline group (P < 0.001). The frequency of side-effects
was not significantly different between the treatment arms. CONCLUSION: The
results of this study suggest that minocycline could be a tolerable and effective
adjuvant in the management of patients with OCD.
PMID- 27488083
TI - The mediating role of relatedness need satisfaction in the relationship between
charitable behavior and well-being: Empirical evidence from China.
AB - Based on self-determination theory, the current research aimed to explore the
potential mediating effect of relatedness need satisfaction on the relationship
between charitable behavior and well-being in the Chinese context. Employing a
cross-sectional design, participants reported data on the aforementioned
variables in Study 1. The results indicated that relatedness need satisfaction
mediated the positive relationship between charitable behavior and hedonic well
being and that between charitable behavior and eudaimonic well-being.
Subsequently, a field experiment was conducted in Study 2. Participants rated
their levels of relatedness need satisfaction and well-being after charitable
donation behaviors were primed. We again observed consistent results.
Specifically, charitable behavior was positively associated with both hedonic and
eudaimonic well-being, and these relationships were mediated by relatedness need
satisfaction. The above findings help to clarify the association between
charitable behavior and people's subjective feelings (i.e., well-being), and they
deepen our understanding of the underlying mechanism from the perspective of
psychological needs satisfaction.
PMID- 27488082
TI - Copulatory plugs inhibit the reproductive success of rival males.
AB - Ejaculated proteins play important roles in reproductive fitness. In many
species, seminal fluid coagulates and forms what has been referred to as a
copulatory plug in the female's reproductive tract. In mice, previous work
demonstrated that knockout males missing a key seminal fluid protein were unable
to form a plug and less successful at siring litters in noncompetitive matings
(one female, one male), probably the result of reduced sperm transport or
insufficient stimulation of the female. Here, we extend these previous studies to
competitive matings (one female, two males) and make two key insights. First,
when first males were unable to form a plug, they lost almost all paternity to
second males to mate. Thus, the copulatory plugs of second males could not rescue
the reduced fertility of first males. Second, we showed that the copulatory plug
of first males effectively blocked fertilization by second males, even if first
males were vasectomized. Taken together, our experiments demonstrated that first
males lost almost all paternity if they never formed a plug. We discuss our
results in the context of natural populations, where in spite of the strong
effects seen here, pregnant female mice regularly carry litters fertilized by
more than one male.
PMID- 27488084
TI - Melanocortin-1 Receptor Polymorphisms and the Risk of Complicated Sepsis After
Trauma: A Candidate Gene Association Study.
AB - OBJECTIVE: The aim of the study was to determine if melanocortin-1 receptor
(MC1R) single nucleotide polymorphisms (SNPs) are associated with complicated
sepsis after trauma. BACKGROUND: Nosocomial infections are an important cause of
morbidity and mortality after trauma. Several SNPs in inflammation-related genes
have been associated with sepsis. MC1R is an anti-inflammatory mediator that may
be involved in the immune response after trauma. PATIENTS AND METHODS: We
genotyped eight common MC1R SNPs in genomic DNA from subjects enrolled in a
previously reported prospective cohort study. Subjects were adult trauma patients
admitted to the intensive care unit at a Level 1 trauma center (2003-2005).
RESULTS: A total of 1,246 subjects were included in the analysis. The majority
were male (70%), severely injured (81%), and injured by a blunt mechanism (89%).
Forty percent developed sepsis, and 23% developed complicated sepsis, which was
defined as sepsis with organ dysfunction. In logistic regression analysis, with
adjustments for age, sex, body mass index, injury severity score, red blood cell
transfusion requirement, and mechanism of injury, the MC1RR163Q variant
(rs885479) was associated with a lower risk of developing complicated sepsis
(adjusted odds ratio [ORadj] = 0.48, 95% confidence interval [CI]: 0.28-0.81, P =
0.006). In a subgroup of 511 subjects with genome-wide SNP data, the association
between the MC1RR163Q variant and complicated sepsis remained significant after
adjusting for genetic substructure (by principal components) and the above
clinical factors (ORadj = 0.30, 95% CI: 0.13-0.70, P = 0.005). CONCLUSIONS:
MC1RR163Q is associated with a lower risk of complicated sepsis after trauma.
Therapeutic targeting of MC1R may be beneficial for trauma patients at risk for
complicated sepsis.
PMID- 27488086
TI - Is Selective Digestive Decontamination Useful for Critically Ill Patients?
AB - In this study we review the rationale for using selective digestive
decontamination (SDD) in critically ill patients, and its effects on clinical
outcomes and rates of infection with antimicrobial-resistant microorganisms. SDD
consists of the application of nonabsorbable antibiotics to the oropharynx and
through a nasogastric or nasoenteral tube, in association with a 4-day course of
an intravenous third-generation cephalosporin. The enteral component aims at
preventing oral and rectal colonization with potentially pathogenic nosocomial
aerobic gram-negative bacilli and yeasts while preserving normal protective
anaerobic enteral flora. The short-course systemic component aims at eradicating
oral endogenous gram-positive bacteria. SDD decreases the risk of nosocomial
infections, and reduces by one-quarter the mortality of patients on mechanical
ventilation in settings with low prevalence of antibiotic resistance. Evidence
from randomized trials suggests that SDD does not increase rates of antimicrobial
resistant microorganisms, and may reduce resistance rates to some antibiotics.
However, several limitations decrease our confidence on these data, particularly
for settings with high baseline rates of antimicrobial-resistant microorganisms.
Although SDD has a clear potential to improve clinical outcomes of critically
patients, its long-term ecologic effects on rates of antimicrobial resistant
require appropriate assessment by large multinational cluster randomized trials.
Before these results are available, the use of SDD cannot be recommended in most
parts of the world, except in settings with very low baseline prevalence of
antibiotic resistance.
PMID- 27488085
TI - Retinoic Acid Improves Incidence and Severity of Necrotizing Enterocolitis by
Lymphocyte Balance Restitution and Repopulation of LGR5+ Intestinal Stem Cells.
AB - Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal disease
of the premature infant. We have recently shown that NEC development occurs after
an increase in proinflammatory CD4Th17 (Th17) cells and reduced anti-inflammatory
forkhead box P3 regulatory T cells (Tregs) to the premature small intestine of
mice and humans, which can be experimentally reversed in mice by administration
of all-trans retinoic acid (ATRA). We have also shown that NEC is characterized
by apoptosis of Lgr5-positive intestinal stem cells (ISCs-Lgr5 cells) within the
crypts of Lieberkuhn, which are subsequently essential for intestinal
homeostasis. We now hypothesize that the normal lymphocyte balance within the
lamina propria of the intestine can be achieved via administration of ATRA which
restores mucosal integrity by preventing the loss of ISCs. Using both in vivo and
in vitro strategies, we now demonstrate that Th17 recruitment and Treg depletion
lead to increased apoptosis within ISC niches, significantly impairing
proliferative capacity and mucosal healing. ATRA exerted its protective effects
by preventing T cell imbalance, ultimately leading to the protection of the ISC
pool preventing the development of NEC in mice. These findings raise the exciting
possibility that dietary manipulations could prevent and treat NEC by modulating
lymphocyte balance and the ISC pool within the newborn small intestine.
PMID- 27488087
TI - Moderate Hypothermia Improves Cardiac and Vascular Function in a Pig Model of
Ischemic Cardiogenic Shock Treated With Veno-Arterial ECMO.
AB - Cardiogenic shock (CS) patients treated with extracorporeal membrane oxygenation
(ECMO) have severe cardiac failure, associated with ischemia-reperfusion. The use
of moderate hypothermia during ischemia-reperfusion syndrome is supported by
experimental data. We therefore studied the effects of moderate hypothermia on
cardiac and vascular function in pig ischemic CS treated with veno-arterial
extracorporeal membrane oxygenation (VA-ECMO). CS was induced in 12 anesthetized
pigs by coronary ligation. After 1 h of CS, VA-ECMO was initiated and pigs were
randomized to normothermia (38 degrees C) or moderate hypothermia (34 degrees C)
during 8 h. Intrinsic cardiac function was measured using a left ventricular
conductance catheter. At the end of the experiment, tissues were harvested for
Western blotting. ECMO associated with norepinephrine infusion and volume
resuscitation increased mean arterial pressure, mixed venous oxygen saturation as
well as carotid, renal, and coronary blood flow without any differences between
normothermia and hypothermia. Hypothermia was associated with less fluid and less
norepinephrine infusion, lower lactate level, and higher urinary output. Vascular
reactivity was superior in hypothermia comparatively to normothermia as expressed
using norepinephrine dose-response curves. Pressure development during isovolumic
contraction, left ventricular ejection fraction, and prerecruitable stroke work
index were higher in the hypothermia group. There were no differences between
normothermia and hypothermia with regard to carotid and mesenteric protein
expression for iNOs, eNOS, and phospho AKt/AKt measured at the end of the
experimentation. The incidence of surgical bleeding and coagulation disorders was
the same in both groups. In conclusion, moderate and rapid hypothermia improves
hemodynamics and cardiac and vascular function in a pig model of ischemic CS
treated with ECMO.
PMID- 27488089
TI - Augmented Passive Immunotherapy with P4 Peptide Improves Phagocyte Activity in
Severe Sepsis.
AB - INTRODUCTION: Antimicrobial resistance threatens to undermine treatment of severe
infection; new therapeutic strategies are urgently needed. Preclinical work shows
that augmented passive immunotherapy with P4 peptide increases phagocytic
activity and shows promise as a novel therapeutic strategy. Our aim was to
determine ex vivo P4 activity in a target population of patients admitted to
critical care with severe infection. METHODS: We prospectively recruited UK
critical care unit patients with severe sepsis and observed clinical course (>=3
months postdischarge). Blood samples were taken in early (<=48 h postdiagnosis, n
= 54), latent (7 days postdiagnosis, n = 39), and convalescent (3-6 months
postdiagnosis, n = 18) phases of disease. The primary outcome measure was killing
of opsonized Streptococcus pneumoniae by neutrophils with and without P4 peptide
stimulation. We also used a flow cytometric whole blood phagocytosis assay to
determine phagocyte association and oxidation of intraphagosomal reporter beads.
RESULTS: P4 peptide increased neutrophil killing of opsonized pneumococci by 8.6%
(confidence interval 6.35-10.76, P < 0.001) in all phases of sepsis, independent
of infection source and microbiological status. This represented a 54.9% increase
in bacterial killing compared with unstimulated neutrophils (15.6%) in early
phase samples. Similarly, P4 peptide treatment significantly increased neutrophil
and monocyte intraphagosomal reporter bead association and oxidation, independent
of infection source. CONCLUSIONS: We have extended preclinical work to
demonstrate that P4 peptide significantly increases phagocytosis and bacterial
killing in samples from a target patient population with severe sepsis. This
study supports the rationale for augmented passive immunotherapy as a therapeutic
strategy in severe sepsis.
PMID- 27488090
TI - Aged Human Stored Red Blood Cell Supernatant Inhibits Macrophage Phagocytosis in
an HMGB1 Dependent Manner After Trauma in a Murine Model.
AB - Red blood cell transfusions in the setting of trauma are a double-edged sword, as
it is a necessary component for life-sustaining treatment in massive hemorrhagic
shock, but also associated with increased risk for nosocomial infections and
immune suppression. The mechanisms surrounding this immune suppression are
unclear. Using supernatant from human packed red blood cell (RBC), we demonstrate
that clearance of Escherichia coli by macrophages is inhibited both in vitro and
in vivo using a murine model of trauma and hemorrhagic shock. We further explore
the mechanism of this inhibition by demonstrating that human-stored RBCs contain
soluble high-mobility group box 1 protein (HMGB1) that increases throughout
storage. HMGB1 derived from the supernatant of human-stored RBCs was shown to
inhibit bacterial clearance, as neutralizing antibodies to HMGB1 restored the
ability of macrophages to clear bacteria. These findings demonstrate that
extracellular HMGB1 within stored RBCs could be one factor leading to immune
suppression following transfusion in the trauma setting.
PMID- 27488091
TI - Evidence of Netosis in Septic Shock-Induced Disseminated Intravascular
Coagulation.
AB - INTRODUCTION: Neutrophils extracellular traps (NETs) have recently emerged as a
new potential link between inflammation, immunity, and thrombosis and could play
a key role in septic shock-induced disseminated intravascular coagulation (DIC)
pathogenesis. The objective of our study was to investigate a potential link
between NETosis and septic shock-induced DIC. METHODS: Twenty patients with
septic shock (10 without and 10 with DIC according to JAAM 2006 score) were
prospectively included in our study. Vascular cell activation was assessed by
microparticle (MP) measurement. NETosis was investigated at days 1, 3, and 7
using two different approaches: probing and measurement of neutrophil DNA
decompaction by neutrophil-side fluorescence light (NEUT-SFL) as recorded by an
automated blood cell cytometer and the assessment of nucleosomes and NETs (DNA
bound myeloperoxidase, DNA-MPO). RESULTS: Endothelial-derived CD105-MPs,
leucocyte-derived CD11a-MPs/leucocyte, and neutrophil-derived CD66b
MPs/neutrophil count ratios significantly increased in DIC compared with non-DIC
patients, indicating on-going cell activation (P <0.05). NEUT-SFL, indicating DNA
decompaction, was significantly higher in DIC patients. Circulating nucleosomes
and DNA-MPO were increased in DIC patients (P <0.05). There were significant
correlations between: nucleosomes and NETs (r = 0.397, P = 0.004), NEUT-SFL and
nucleosomes (r = 0.243, P = 0.032), NEUT-SFL and DNA-MPO (r = 0.266, P = 0.024).
CONCLUSION: NEUT-SFL, NETs, and elevated nucleosome concentrations were all
correlated to DIC (P <0.05). We have shown that NETosis is significantly
correlated to septic shock-induced DIC.
PMID- 27488092
TI - The Airway Microbiome at Birth.
AB - Alterations of pulmonary microbiome have been recognized in multiple respiratory
disorders. It is critically important to ascertain if an airway microbiome exists
at birth and if so, whether it is associated with subsequent lung disease. We
found an established diverse and similar airway microbiome at birth in both
preterm and term infants, which was more diverse and different from that of older
preterm infants with established chronic lung disease (bronchopulmonary
dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were
seen from birth to the development of bronchopulmonary dysplasia in extremely
preterm infants. Genus Lactobacillus was decreased at birth in infants with
chorioamnionitis and in preterm infants who subsequently went on to develop lung
disease. Our results, taken together with previous literature indicating a
placental and amniotic fluid microbiome, suggest fetal acquisition of an airway
microbiome. We speculate that the early airway microbiome may prime the
developing pulmonary immune system, and dysbiosis in its development may set the
stage for subsequent lung disease.
PMID- 27488094
TI - Hepatocellular carcinoma developed in a living donor after left lobe donation: a
case for caution.
AB - Although it has been recognized that those who are positive for anti-hepatitis B
core antibody (anti-HBcAb) and negative for hepatitis B surface antigen (HBsAg)
with normal liver function could be donors for living donor liver transplantation
under appropriate prophylaxis, the negative impact of positive HBcAb on such
donors themselves has not been reported. We present a case of a living donor with
positive HBcAb, who donated his left lobe for his sister with unresectable giant
hepatic hemangioma, and the donor himself developed a de novo hepatocellular
carcinoma (HCC) 10 years after donation. He had been lost from the follow-up
program since 1 year after donation. Imaging studies showed a heterogeneously
enhanced mass compatible with HCC, which was 9 cm in size with portal invasion
into the anterior portal vein of the remnant liver. Re-laparotomy for hepatectomy
with the removal of the tumor thrombus in the anterior portal vein of the remnant
liver was carried out, and he is free from recurrence 6 months after surgery on
prophylactic sorafenib. At our institute, 58 (9.6%) donors among the 603 living
donors were anti-HBcAb positive and anti-HBsAg negative, and we started regular
HCC surveillance using sonogram every 6 months for these patients.
PMID- 27488093
TI - Predictive Immunohistochemical Markers Related to Drug Selection for Patients
Treated with Sunitinib or Sorafenib for Metastatic Renal Cell Cancer.
AB - Targeted drug decisions in metastatic renal cell carcinoma are exclusively made
on the basis of clinical criteria. We investigated whether these biomarkers (HIF
1alpha, HIF-2alpha, CAIX, VEGF, VEGFR1, VEGFR2, VEGFR3, PDGFB, PDGFRA, PDGFRB,
CD31, CD44, bcl-xL, KIT, p21, CXCR4, PTEN, (CSF)-1R, RET, and FLT-3) can
predictive the different effects between sunitinib and sorafenib treatments and
are available to guide targeted drug selection. We enrolled all patients who
underwent nephrectomy with postoperative sunitinib- or sorafenib-treatment at our
institution from 2007 to 2012. Immunohistochemical approach was applied to assess
the potential differential effects of immunostainings between sunitinib- and
sorafenib-treated groups. We found that patients with high HIF-2alpha, CD31
expression showed greater relative PFS and OS benefit and patients with high CAIX
expression presented greater relative OS benefit from sunitinib than from
sorafenib, patients with high VEGFR1 or PDGFRB expression levels exhibited worse
relative PFS benefit from sunitinib than from sorafenib. Namely high HIF-2alpha,
CD31, and CAIX expression levels along with low VEGFR1 and PDGFRB expression
levels improved the benefit of sunitinib treatment compared with sorafenib
treatment. These results can identify whether patients can benefit more from
sunitinib or sorafenib for drug selection guidance, eventually with precision
medicine.
PMID- 27488095
TI - Papain-like cysteine proteases as hubs in plant immunity.
AB - 902 I. 902 II. 903 III. 903 IV. 903 V. 905 VI. 905 VII. 905 906 References 906
SUMMARY: Plants deploy a sophisticated immune system to cope with different
microbial pathogens and other invaders. Recent research provides an increasing
body of evidence for papain-like cysteine proteases (PLCPs) being central hubs in
plant immunity. PLCPs are required for full resistance of plants to various
pathogens. At the same time, PLCPs are targeted by secreted pathogen effectors to
suppress immune responses. Consequently, they are subject to a co-evolutionary
host-pathogen arms race. When activated, PLCPs induce a broad spectrum of defense
responses including plant cell death. While the important role of PLCPs in plant
immunity has become more evident, it remains largely elusive how these enzymes
are activated and which signaling pathways are triggered to orchestrate different
downstream responses.
PMID- 27488096
TI - Early silicification of leaves and roots of seedlings of a panicoid grass grown
under different conditions: anatomical relations and structural role.
AB - Grasses accumulate high amounts of silica deposits in tissues of all their
organs, especially at mature stage. However, when and under which conditions do
grass seedlings begin to produce these silica deposits and their relation with
anatomy and development is little known. Here we investigated the silicification
process in the first leaves and roots of seedlings of Bothriochloa laguroides
grown in different substrate and Si treatments. The distribution and content of
silica deposits in the organs of the seedlings grown under different conditions
were analyzed through staining techniques and SEM-EDAX analyses. Leaf silica
deposits were accumulated 3-4 days after the first leaf emergence, also under low
silica solution (0.17-0.2 mM). Their location was mainly restricted to short
costal cells from basal sectors, and scarcely in trichomes and xylem at tips.
Silica content in leaves increased with the age of the seedlings. Roots presented
dome-shaped silica aggregates, between 4-12 MUm of diameter, located in the inner
tangential wall of endodermal cells and similar to those produced at maturity.
Silicification begins early in the first photosynthetic leaf, and silica
distribution is opposite to that found in mature plants, mainly restricted to
basal sectors, probably acting as a reinforcing element. The fast incorporation
of solid amorphous silica in leaves and roots, may be useful for farm
applications in species that are Si-fertilized.
PMID- 27488097
TI - Prioritizing individual genetic variants after kernel machine testing using
variable selection.
AB - Kernel machine learning methods, such as the SNP-set kernel association test
(SKAT), have been widely used to test associations between traits and genetic
polymorphisms. In contrast to traditional single-SNP analysis methods, these
methods are designed to examine the joint effect of a set of related SNPs (such
as a group of SNPs within a gene or a pathway) and are able to identify sets of
SNPs that are associated with the trait of interest. However, as with many multi
SNP testing approaches, kernel machine testing can draw conclusion only at the
SNP-set level, and does not directly inform on which one(s) of the identified SNP
set is actually driving the associations. A recently proposed procedure, KerNel
Iterative Feature Extraction (KNIFE), provides a general framework for
incorporating variable selection into kernel machine methods. In this article, we
focus on quantitative traits and relatively common SNPs, and adapt the KNIFE
procedure to genetic association studies and propose an approach to identify
driver SNPs after the application of SKAT to gene set analysis. Our approach
accommodates several kernels that are widely used in SNP analysis, such as the
linear kernel and the Identity by State (IBS) kernel. The proposed approach
provides practically useful utilities to prioritize SNPs, and fills the gap
between SNP set analysis and biological functional studies. Both simulation
studies and real data application are used to demonstrate the proposed approach.
PMID- 27488099
TI - Is IGF-1 a key player in the pathogenesis of acromegaly-associated cutis verticis
gyrata?
PMID- 27488098
TI - Urinary excretion of Citrus flavanones and their major catabolites after
consumption of fresh oranges and pasteurized orange juice: A randomized cross
over study.
AB - SCOPE: Orange juice contains flavanones including hesperidin and narirutin,
albeit at lower concentrations as compared to orange fruit. Therefore, we
compared bioavailability and colonic catabolism of flavanones from orange juice
to a 2.4-fold higher dose from fresh oranges. METHODS AND RESULTS: Following a
randomized two-way cross-over design, 12 healthy subjects consumed a test meal
comprising either fresh oranges or pasteurized orange juice, delivering 1774 and
751 MUmol of total Citrus flavanones, respectively. Deglucuronidated and
desulfated hesperetin, naringenin, and the flavanone catabolites 3-(3'-hydroxy-4'
methoxyphenyl)propionic acid, 3-(3'-hydroxyphenyl)hydracrylic acid, 4
hydroxyhippuric acid, and hippuric acid were quantitated in 24-h urine by UHPLC
MS/MS. Differences in urinary hesperetin excretion were found to be
nonsignificant (p = 0.5209) both after consumption of orange fruit (21.6 +/- 8.0
MUmol) and juice (18.3 +/- 7.2 MUmol). By analogy, postprandial flavanone
catabolite excretions were highly similar between treatments. Excretion of 3-(3'
hydroxy-4'-methoxyphenyl)propionic acid was inversely related to that of
hesperetin, illustrating the catabolite/precursor relationship. CONCLUSION:
Despite 2.4-fold higher doses, excretion of flavanones from ingested fresh orange
fruit did not differ from that following orange juice consumption, possibly due
to a saturation of absorption or their entrapment in the fiber-rich matrix of the
fruit.
PMID- 27488100
TI - Knowledge and beliefs of young people about medicines in the UK.
AB - OBJECTIVES: To investigate knowledge and beliefs regarding medicines among young
people in the South-East of England. METHODS: A cross-sectional survey was
conducted among young people aged 12-17 years in three state secondary schools
which participated in the Pharmacy and Biomedical Sciences Outreach Program (POP)
- scientific workshops in south-east England. KEY FINDINGS: One hundred
questionnaires were successfully completed giving a response rate of 75%. The
median knowledge score was 62.3% (+/-19.8). Increase in knowledge of medicines
was positively associated with increase in age and with a positive belief about
medicines. One of the questions answered that scored less than 50% was concerning
the use of antibiotics. CONCLUSIONS: Knowledge of medicines appeared to be
adequate among young people and was higher with a positive belief about
medicines. However, there was variability in how well different questions were
answered suggesting inclusion in the school curriculum would be beneficial in
order to reduce the misinformation that was apparent, particularly regarding the
potential non-adherence to antibiotics.
PMID- 27488101
TI - Osteoarthritis is associated with symptoms of common mental disorders among
former elite athletes.
AB - PURPOSE: The primary aim was to establish the association between osteoarthritis
(OA) and the occurrence and comorbidity of symptoms of common mental disorders
(CMD: distress, anxiety/depression, sleep disturbance, adverse alcohol use) in a
group of former elite athletes (rugby, football, ice hockey, Gaelic sports and
cricket). A secondary aim was to explore this association in the subgroups of
sports. METHODS: Cross-sectional analysis was performed on the baseline
questionnaires from five prospective cohort studies conducted between April 2014
and January 2016 in former elite athletes of rugby, football, ice hockey, Gaelic
sports and cricket. The presence of OA (diagnosed by a medical professional) was
examined with a single question, and symptoms of CMD were evaluated through
multiple validated questionnaires (4DSQ, GHQ-12, PROMIS, AUDIT-C). RESULTS: There
was a significant association between OA and symptoms of distress (OR 1.7, 95 %
CI 1.2-2.6), sleep disturbance (OR 1.6, 95 % CI 1.1-2.3), adverse alcohol use (OR
1.8, 95 % CI 1.2-2.6) and a comorbidity of symptoms of CMD (OR 1.5, 95 % CI 1.0
2.1) in former elite athletes. CONCLUSION: OA might be a risk factor for
developing symptoms of CMD in former elite athletes. The clinical relevance of
this study is that an interdisciplinary approach to the clinical care and support
of former elite athletes after their careers is advocated as the interaction
between the physical and mental health issues occurring on the long term is
complex. Monitoring OA among former elite athletes should be empowered while
strategies to prevent symptoms worsening should be developed and implemented. The
self-awareness, prevention and care of mental health problems that might occur
after a professional sports career should also be addressed. LEVEL OF EVIDENCE:
Level III.
PMID- 27488103
TI - Theoretical study of coupling p-aminothiophenol to hydroazo- and azo-adducts on
Au(111).
AB - Aminothiophenol/Au(111) has been adopted as an exemplary model in plasmonics
research, including surface-enhanced Raman spectroscopy, due to its high
plasmonic-induced spectral-signal enhancement. The present work was aimed at
clarifying whether aminothiophenol on Au(111) is chemically stable in the absence
of any photo- and plasmonic-induced effects. Briefly, first-principles
calculations were employed to track the detailed mechanism of oxidative coupling
of p-aminothiophenol (PATP) to its azo-adduct with an N = N bond, i.e., p,p'
dimercaptoazobenzene (DMAB). Our results show the following: first, in the
presence of adsorbed O2, PATP fractures its N-H bond and transfers the hydrogen
to a nearby oxygen. This pathway is more favorable than the transfer of H to Au,
but the activation barrier of 0.9 eV is still too high for the reaction to occur
in the absence of thermal-, photo-, or plasmonic-activation. If this bar can be
lifted, two such dehydrogenated PATP can couple themselves to form an adduct with
a N-N bond, i.e., p,p'-dimercaptohydroazobenzene (DMHAB), and this reaction is
exoergic with an energy barrier of 0.57 eV. Again, this step is slow in the
absence of moderate thermal activation or photo-/plasmonic-activation. Finally,
dehydrogenation of DMHAB gives the azo-adduct of DMAB, and this reaction is
spontaneous, with no energy barrier.
PMID- 27488102
TI - Molecular cloning and in silico characterization of knottin peptide, U2-SCRTX
Lit2, from brown spider (Loxosceles intermedia) venom glands.
AB - Inhibitor cystine knots (ICKs) are a family of structural peptides with a large
number of cysteine residues that form intramolecular disulfide bonds, resulting
in a knot. These peptides are involved in a variety of biological functions
including predation and defense, and are found in various species, such as
spiders, scorpions, sea anemones, and plants. The Loxosceles intermedia venom
gland transcriptome identified five groups of ICK peptides that represent more
than 50 % of toxin-coding transcripts. Here, we describe the molecular cloning of
U2-Sicaritoxin-Lit2 (U2-SCRTX-Lit2), bioinformatic characterization, structure
prediction, and molecular dynamic analysis. The sequence of U2-SCRTX-Lit2
obtained from the transcriptome is similar to that of MU-Hexatoxin-Mg2, a peptide
that inhibits the insect Nav channel. Bioinformatic analysis of sequences
classified as ICK family members also showed a conservation of cysteine residues
among ICKs from different spiders, with the three dimensional molecular model of
U2-SCRTX-Lit2 similar in structure to the hexatoxin from MU-hexatoxin-Mg2a.
Molecular docking experiments showed the interaction of U2-SCRTX-Lit2 to its
predictable target-the Spodoptera litura voltage-gated sodium channel (SlNaVSC).
After 200 ns of molecular dynamic simulation, the final structure of the complex
showed stability in agreement with the experimental data. The above analysis
corroborates the existence of a peptide toxin with insecticidal activity from a
novel ICK family in L. intermedia venom and demonstrates that this peptide
targets Nav channels.
PMID- 27488104
TI - Effect of electric charging on the velocity of water flow in CNT.
AB - The role of electrical charge in controlling the velocity of water molecules in a
finite single-walled carbon nanotube (CNT) was studied in detail using molecular
dynamics simulation. Different test cases were examined to determine the
parameters affecting the control of water-flow velocity in CNT upon electrically
charging the surface of a CNT. The results showed that charge magnitude and
volume, as well as the charging scenario, are the parameters having greatest
effect. The implementation of electric charge on the surface of a CNT was
demonstrated to decrease the resistance of CNT to incoming water flow at the
entrance, but to increase friction-type resistance to flow along the CNT.
Therefore, through controlling the magnitude of electric charge, water flow
through the CNT may be accelerated, or decelerated. The results show that the
velocity of molecular flow in the CNT increases to a maximum value, and then
decreases with electric charge regardless of its sign. In the case studied here,
this maximum velocity occurs at electric charging of +/-0.25e/atom. It was also
shown that, to reach similar flow velocities in a CNT, it is not sufficient to
merely implement equal volumes of electric charge, where the volume of electric
charging is defined as charge magnitude * charging time. In fact , both magnitude
of charging and volume of electric charging must be equal to each other. These
findings, together with options to implement scenarios with alternative charging,
provide the means to effectively adjust desired velocities in a CNT.
PMID- 27488106
TI - 54th ISCEV Symposium.
PMID- 27488105
TI - Changes in miR-221/222 Levels in Invasive and In Situ Carcinomas of the Breast:
Differences in Association with Estrogen Receptor and TIMP3 Expression Levels.
AB - BACKGROUND: Breast cancer (BC) is a heterogeneous group of diseases that still
represents a major cause of death in the female population. MicroRNAs (miRNAs,
miRs), such as miR-221 and miR-222, have been shown to be involved in BC
pathology by acting via its target genes such as tissue inhibitor of
metalloproteinase 3 (TIMP3). OBJECTIVES: The main goals of this study were to
find differences in miR-221/222 levels of expression in BC groups based on
invasiveness, and to investigate the association with estrogen receptor (ER),
TIMP3 messenger RNA (mRNA) levels, and clinicopathological characteristics of
patients and tumors. METHODS: In this study, we measured levels of miR-221/222 in
63 breast tissue samples by quantitative reverse transcription-polymerase chain
reaction (qRT-PCR) using TaqMan(r) technology and immunohistochemistry. RESULTS:
miR-221/222 levels varied significantly across groups based on invasiveness (P <
0.001). In in situ tumors, miR-221 and miR-222 were negatively associated with ER
(P = 0.001, r = -0.714, and P = 0.013, r = -0.585, respectively). In invasive
breast carcinomas associated with non-invasive tumors, miR-222 was inversely
associated with ER (P = 0.039, r = -0.620). Pure invasive BCs showed a positive
correlation of miR-221 and miR-222 with TIMP3 mRNA levels (P = 0.008, r = 0.508,
and P = 0.010, r = 0.497, respectively). CONCLUSION: An increase in miR-221/222
might be an important event for in situ carcinoma formation, and miR-221/222 may
be important molecules that highlight potential differences between invasive
breast carcinomas associated with non-invasive and pure invasive BCs.
PMID- 27488107
TI - Roles of mitophagy in cellular physiology and development.
AB - The autophagic degradation of mitochondria, or mitophagy, has been shown to occur
in eukaryotic cells under various physiological conditions. Broadly, these fall
into two categories: quality-control related mitophagy and developmentally
induced mitophagy. Quality-control related mitophagy, which is the
lysosomal/vacuolar degradation of malfunctioning or superfluous mitochondria, is
an important housekeeping function in respiring eukaryotic cells. It plays an
essential role in physiological homeostasis and its deregulation has been linked
to the progression of late-onset diseases. On the other hand, developmental
processes such as reticulocyte maturation have also been shown to involve
mitophagy. Importantly, there are clear differences between these processes.
Unlike our knowledge of the more general degradation of soluble cytosolic content
during starvation-induced macroautophagy, the mechanisms involved in the
selective autophagic degradation of mitochondria have only recently begun to
receive significant attention. Here, we review the current literature on these
topics and proceed to provide specific examples from yeast and mammalian systems.
Finally, we cover experimental approaches, with a focus on proteomic methods
dedicated to the study of mitophagy in different systems.
PMID- 27488108
TI - [Ponseti method for treatment of idiopathic clubfoot].
AB - OBJECTIVE: Pain-free, plantigrade, functional foot through gentle manipulation
without extended surgery and with decreased probability of relapse. INDICATIONS:
Idiopathic clubfoot; neurogenic and secondary clubfeet. CONTRAINDICATIONS: None.
SURGICAL TECHNIQUE: Simultaneous correction of all components of the clubfoot.
Mainly conservative, with serial casts. Slight supination to address the cavus
and increasing abduction to align the midfoot bones while putting counter
pressure on the head of the talus. Surgery primarily only to correct the equinus,
which can often not be accomplished through casting, and consists of a simple
subcutaneous section. Due to tendency to relapse, further surgery might be
necessary, followed by serial casting. Remaining deformity can be treated by
percutaneous lengthening of the Achilles tendon, percutaneous release of the
plantar fascia or a transfer of the tibialis anterior tendon to the third
cuneiform. POSTOPERATIVE MANAGEMENT: Abduction orthosis for stabilization of the
clinical result 24 h/day for 3 months, then only at night- and naptime through
end of the third year of life. Follow-up every 3-4 months.
PMID- 27488109
TI - DNA damage after chronic oxytocin administration in rats: a safety yellow light?
AB - Adjuvant therapy is a common therapeutic strategy used for schizophrenia
management. Oxytocin has shown promising results as antipsychotic adjuvant in
patients with schizophrenia. Although short-term clinical studies have indicated
tolerability and no major side-effect manifestation, long-term studies remain
needed. In this study, we investigated whether oxytocin chronic administration in
rats may lead to brain DNA damage by comet assay. Our results suggest that 21 and
56-day treatment with once daily intraperitoneal oxytocin (0.1, 1.0 and 10.0
mg/kg) may cause substantial DNA damage in hippocampus. We have not found
differences on body weight gain. Our findings also point that further clinical
and preclinical studies evaluating oxytocin safety after chronic exposure are
necessary.
PMID- 27488111
TI - Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains
of rats with streptozotocin-induced diabetes.
AB - The central nervous system is one of the most vulnerable organs affected by the
oxidative stress associated with diabetes mellitus. Healthy food provides an
important source for antioxidants. Therefore, the protective effect of Cucumis
melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of
diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6
rats each were assigned into a normal control group and four diabetic groups.
Diabetes was induced in rats by a single intraperitoneal injection of
streptozotocin (STZ; 60 mg/kg bw). One of the four diabetic groups was left
untreated and was considered as a diabetic control group while the three other
groups were treated with C. melo var. flexuosus leaf extract at the doses of 30,
60 and 120 mg/kg bw for a period of 30 days. After completion of experimental
duration plasma and brains were used for evaluating biochemical changes. The
obtained data showed that C. melo var. flexuosus leaf extract treatment lowered
blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha,
interleukin levels, brain malondialdehyde content and caspase-3 activity.
Furthermore, the treatment resulted in a marked increase in plasma dopamine,
melatonin, brain vascular endothelial growth factor-A levels, brain catalase and
superoxide dismutase activities. From the present study, it can be concluded that
the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against
oxidative damage associated with diabetes.
PMID- 27488110
TI - SB203580 reverses memory deficits and depression-like behavior induced by
microinjection of Abeta1-42 into hippocampus of mice.
AB - A high co-morbidity between Alzheimer's disease (AD) and depression suggests
there might be similar mechanisms underlying the course of these diseases.
Previous studies have shown that p38MAPK plays a critical role in the
pathophysiology of AD and depression. However, little is known about whether
SB203580, a selective inhibitor of p38MAPK, may protect against AD-associated
cognitive impairments and depression-like behavior, simultaneously. Herein, we
have shown, for the first time, that SB203580 may reverse memory impairments and
depression-like behavior induced by hippocampal infusion of beta-amyloid 1-42
(Abeta1-42), as measured by novel object recognition, Morris water maze, tail
suspension and forced-swimming tests. In addition, phorbol 12-myristate 13
acetate (PMA), a PKC activator which also activates p38MAPK, significantly
abolished the effects of SB203580. Moreover, Abeta1-42 causes increased
phosphorylation of p38MAPK and decreased phosphorylation of Ser9-glycogen
synthase kinase 3beta (GSK3beta) and cAMP-response element binding protein (CREB)
in the hippocampus of mice, which could be significantly reversed by SB203580.
Our results suggest that SB203580 reversed Abeta1-42-induced cognitive
impairments and depression-like behavior via inhibiting p38MAPK signaling
pathway, which not only supports p38MAPK as a therapeutic target for AD
associated cognitive dysfunction and depression-like behavior, but also provides
experimental basis for the use of SB203580 in co-morbidity of AD and depression.
PMID- 27488112
TI - A longitudinal study of patients with cirrhosis treated with L-ornithine L
aspartate, examined with magnetization transfer, diffusion-weighted imaging and
magnetic resonance spectroscopy.
AB - The presence of overt hepatic encephalopathy (HE) is associated with structural,
metabolic and functional changes in the brain discernible by use of a variety of
magnetic resonance (MR) techniques. The changes in patients with minimal HE are
less well documented. Twenty-two patients with well-compensated cirrhosis, seven
of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques,
including T1- and T2-weighted, magnetization transfer and diffusion-weighted
imaging and proton magnetic resonance spectroscopy sequences. Studies were
repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results
were compared with data obtained from 22 aged-matched healthy controls. There was
no difference in mean total brain volume between patients and controls at
baseline. Mean cerebral magnetization transfer ratios were significantly reduced
in the globus pallidus and thalamus in the patients with cirrhosis irrespective
of neuropsychiatric status; the mean ratio was significantly reduced in the
frontal white matter in patients with minimal HE compared with healthy controls
but not when compared with their unimpaired counterparts. There were no
significant differences in either the median apparent diffusion coefficients or
the mean fractional anisotropy, calculated from the diffusion-weighted imaging,
or in the mean basal ganglia metabolite ratios between patients and controls.
Psychometric performance improved in 50 % of patients with minimal HE following
LOLA, but no significant changes were observed in brain volumes, cerebral
magnetization transfer ratios, the diffusion weighted imaging variables or the
cerebral metabolite ratios. MR variables, as applied in this study, do not
identify patients with minimal HE, nor do they reflect changes in psychometric
performance following LOLA.
PMID- 27488113
TI - Postoperative Bleeding and Leakage after Sleeve Gastrectomy: a Single-Center
Experience.
PMID- 27488115
TI - Cytosolic Ku70 regulates Bax-mediated cell death.
AB - The first known function of Ku70 is as a DNA repair factor in the nucleus. Using
neuronal neuroblastoma cells as a model, we have established that cytosolic Ku70
binds to the pro-apoptotic protein Bax in the cytosol and blocks Bax's cell death
activity. Ku70-Bax binding is regulated by Ku70 acetylation in that when Ku70 is
acetylated Bax dissociates from Ku70, triggering cell death. We propose that Ku70
may act as a survival factor in these cells such that Ku70 depletion triggers Bax
dependent cell death. Here, we addressed two fundamental questions about this
model: (1) Does all Bax, which is a cytosolic protein, bind to all cytosolic
Ku70? and (2) Is Ku70 a survival factor in cells types other than neuronal
neuroblastoma cells? We show here that, in neuronal neuroblastoma cells, only a
small fraction of Ku70 binds to a small fraction of Bax; most Bax is monomeric.
Interestingly, there is no free or monomeric Ku70 in the cytosol; most cytosolic
Ku70 is in complex with other factors forming several high molecular weight
complexes. A fraction of cytosolic Ku70 also binds to cytosolic Ku80, Ku70's
binding partner in the nucleus. Ku70 may not be a survival factor in some cell
types (Ku70-depletion less sensitive) because Ku70 depletion does not affect
survival of these cells. These results indicate that, in addition to Ku70
acetylation, other factors may be involved in regulating Ku70-Bax binding in the
Ku70-depletion less sensitive cells because Ku70 acetylation in these cells is
not sufficient to dissociate Bax from Ku70 or to activate Bax.
PMID- 27488114
TI - Pregnancy Following Bariatric Surgery-Medical Complications and Management.
AB - Bariatric surgery is most commonly carried out in women of childbearing age.
Whilst fertility rates are improved, pregnancy following bariatric surgery poses
several challenges. Whilst rates of many adverse maternal and foetal outcomes in
obese women are reduced after bariatric surgery, pregnancy is best avoided for 12
24 months to reduce the potential risk of intrauterine growth retardation.
Dumping syndromes are common after bariatric surgery and can present diagnostic
and therapeutic challenges in pregnancy. Early dumping occurs due to osmotic
fluid shifts resulting from rapid gastrointestinal food transit, whilst late
dumping is characterized by a hyperinsulinemic response to rapid absorption of
simple carbohydrates. Dietary measures are the mainstay of management of dumping
syndromes but pharmacotherapy may sometimes become necessary. Acarbose is the
least hazardous pharmacological option for the management of postprandial
hypoglycemia in pregnancy. Nutrient deficiencies may vary depending on the type
of surgery; it is important to optimize the nutritional status of women prior to
and during pregnancy. Dietary management should include adequate protein and
calorie intake and supplementation of vitamins and micronutrients. A high
clinical index of suspicion is required for early diagnosis of surgical
complications of prior weight loss procedures during pregnancy, including small
bowel obstruction, internal hernias, gastric band erosion or migration and
cholelithiasis.
PMID- 27488116
TI - Proteomic analysis of differentially expressed proteins in vitreous humor of
patients with retinoblastoma using iTRAQ-coupled ESI-MS/MS approach.
AB - There is close proximity of vitreous humor with the tumor bulk in eyes with
retinoblastoma. This renders vitreous humor a promising source to evaluate
disease-specific protein targets in retinoblastoma. We studied the differential
proteome of vitreous fluid in retinoblastoma tumors (n = 4) as compared to
controls (n = 4). The vitreous humor was depleted off the high abundant fraction
using MARS-6 affinity column. Subsequently, the tryptic peptides were derivatised
with iTRAQ labels. The labelled peptides were pooled and subjected to
fractionation using bRPLC. This was followed by protein identification and
quantification using electrospray ionisation mass spectrometry (ESI-MS/MS)
approach. The identified proteins were subjected to bioinformatics analysis
utilizing PANTHER 7.0 and IPA software. Four hundred and thirty-one non-redundant
(362 upregulated and 69 downregulated) proteins (>=2 unique peptides, +/- 1.5
folds, p < 0.05) were identified. The majority of the proteins were cytoplasmic
(40 %), majorly involved in catalytic (32.7 %) and binding activities (26.3 %).
Highly deregulated proteins included MMP2, TNC, CD44, SUZ12 and CRABP1. The
protein expression of GFAP, CRABP1, MMP2 and TNC was validated by western
blotting. Pathway and network analyses revealed p38MAPK and Akt signalling to be
the most significantly regulated pathways in retinoblastoma. This is the first
report of differential vitreous proteome of retinoblastoma and highlights novel
protein targets, such as MMP2, TNC and CRABP1. Further investigations into
unravelling the biological role of the proteins and their prospects of being
utilised as potential candidates in therapeutics are warranted.
PMID- 27488117
TI - IQGAP1 gene silencing induces apoptosis and decreases the invasive capacity of
human hepatocellular carcinoma cells.
AB - IQ motif-containing GTPase-activating proteins (IQGAPs) belong to a conserved
family, and they are involved in various intracellular processes. IQGAP1 is
expressed in all cells, while IQGAP2 and IQGAP3 are mainly expressed in hepatic
cells. IQGAP1 has been suggested to be an oncogene, while IQGAP2 is considered a
tumor-suppressor gene. However, the relationship between RAS family genes and
IQGAP genes remains unclear. We recently demonstrated this interaction in a
chemically induced mouse liver cancer. In this study, IQGAP1 expression was
partially silenced in human hepatocellular carcinoma (HepG2) cells. We
investigated the impact of IQGAP1 silencing on the interactions of IQGAP and RAS
with several apoptotic proteins, including caspase-3 (CASP3), BCL2-associated X
protein (BAX), and B-cell leukemia/lymphoma 2 (BCL2). Additionally, we
investigated the effects of the interactions of these genes on cell viability,
proliferation, apoptosis, and invasive capacity. IQGAP1 siRNA-treated HepG2 cells
showed lower invasive capacity than the control cells, and this reduction was
time- and vector concentration-dependent. In addition, IQGAP1 silencing resulted
in significantly lower IQGAP1 level and subsequently higher IQGAP2 and IQGAP3
expression in HepG2 cells than in the control. Flow cytometry analyses indicated
that the silencing of IQGAP1 can induce early and late apoptosis in HepG2 cells.
Additionally, IQGAP2, IQGAP3, CASP3, and BAX were upregulated whereas IQGAP1 and
BCL2 were downregulated in the siRNA-treated cells. Furthermore, we observed that
the mRNA levels of HRAS, KRAS, NRAS, and MRAS decreased upon IQGAP1 silencing.
These findings indicate that IQGAP1 potentially regulates the expression of IQGAP
and RAS gene families and demonstrate its regulatory role in the apoptotic
network. Taken together, our findings suggest that IQGAP1 silencing plays crucial
roles in the apoptosis of HepG2 cells and lowers their proliferative and invasive
capacities.
PMID- 27488118
TI - Selvester QRS score and total perfusion deficit calculated by quantitative gated
single-photon emission computed tomography in patients with prior anterior
myocardial infarction in the coronary intervention era.
AB - Selvester QRS scoring system has an advantage of being inexpensive and easily
accessible for estimating myocardial infarct (MI) size. We assessed the
correlation and agreement between QRS score and total perfusion deficit (TPD)
calculated by quantitative gated single-photon emission computed tomography (QGS)
in patients with prior anterior MI undergoing coronary intervention. Sixty-six
patients with prior anterior MI and 66 age- and sex-matched control subjects were
enrolled. QRS score was obtained using a 50-criteria and 31-point system. QRS
score was significantly higher in patients with prior anterior MI than control
subjects (12.8 +/- 8.9 vs 1.1 +/- 2.7 %, p < 0.001). In overall patients (n =
132), QRS score was correlated well with TPD (r = 0.81, p < 0.001). This good
correlation was found even in patients with TPD <=40 % (n = 126) or in patients
with TPD <=30 % (n = 117). In overall patients, MI size estimated by QRS score
was 7.0 +/- 8.8 %, which was significantly smaller than TPD, 11.4 +/- 14.0 % (p <
0.001). Bland-Altman plot showed that there was an increasing difference between
QRS score and TPD with increasing MI size. When Blant-Altman plots were applied
to patients with TPD <=40 % and further in patients with TPD <=30 %, the
difference between QRS score and TPD became smaller, and the agreement became
better. In overall patients, QRS score was correlated well with QGS measurements,
such as end-diastolic volume (r = 0.62, p < 0.001), end-systolic volume (r =
0.67, p < 0.001), or ejection fraction (r = -0.73, p < 0.001). Our results
suggest that QRS score reflects TPD well in patients with prior anterior MI,
whose TPD is less than approximately 30 % even in the coronary intervention era.
PMID- 27488119
TI - Microparticles in patients undergoing transcatheter aortic valve implantation
(TAVI).
AB - Degenerative aortic stenosis (AS) is the most frequent form of acquired valvular
heart disease. AS is known to entail endothelial dysfunction caused by increased
mechanical shear stress leading to elevated circulatory levels of microparticles.
Endothelial and platelet microparticles (EMP and PMP) are small vesicles that
originate from activated cells and thrombocytes. We sought to evaluate whether
transcatheter aortic valve implantation (TAVI) procedure would elicit effects on
circulating EMP and PMP. 92 patients undergoing TAVI procedure for severe AS were
included in this study. Samples were obtained at each visit before TAVI, 1 week
post-procedure and at 1, 3 and after 6 months after TAVI and were evaluated using
flow cytometry. A 12 month clinical follow-up was also performed. CD62E+ EMP
concentration before TAVI was 21.11 % (+/-6.6 % SD) and declined to 20.99 % (+/
6.8 % SD) after 1 week, to 16.63 % (+/-5.4 % SD, p < 0.0001) after 1 month, to
17.08 % (+/-4.6 % SD, p < 0.0001) after 3 months and to 15.94 % (+/-5.4 % SD, p <
0.0001) after 6 months. CD31+/CD42b-, CD31+/Annexin+/- EMP remained unchanged.
CD31+/CD41b+ PMP evidenced a slight, but statistically significant increase after
TAVI and remained elevated during the entire follow-up. Apart from a procedure
related improvement in echocardiographic parameters, TAVI procedure led also to a
decline in CD62E+ EMP. The reduction in pressure gradients with less hemodynamic
shear stress seems also to have beneficially affected endothelial homeostasis.
PMID- 27488120
TI - Acute and Chronic Complications in Patients with Ductal Carcinoma in Situ Treated
with Intraoperative Radiation Therapy.
AB - Intraoperative radiation therapy (IORT) delivers radiation therapy directly to
the tumor bed at the time of surgery. Minimal data are available regarding IORT
complications in patients diagnosed with ductal carcinoma in situ (DCIS) using
the Xoft(r) Axxent eBx(r) System. 146 patients with pure DCIS received X-ray
based IORT therapy using the Xoft(r) Axxent eBx(r) System at Hoag Memorial
Hospital Presbyterian between June 2010 to April 2016 and were accrued to an IORT
data registry study. The protocols were approved by the institutional review
board and met the guidelines of their responsible governmental agency. Data were
collected at 1 week, 1 month, 6 months, 1 year, and thereafter yearly. Acute
complications were defined as those occurring within the first month. Chronic
complications were those that persisted beyond 6 months. Acute complications were
observed in 18% of patients and included hematomas that required drainage, an
infection treated with antibiotics, and erythema. Chronic complications were
observed in 12% of patients and included a seroma, fibrosis and
hyperpigmentation. The majority of acute and chronic problems were mild (Grade
I). If Grade I erythema, fibrosis, and hyperpigmentation are not included, only
11/146 patients (7.5%) had significant complications. The rate of acute and
chronic complications from X-ray IORT in DCIS patients was low compared to
historical toxicity rates observed in DCIS patients treated with whole breast
irradiation. Our data indicate that X-ray IORT can be utilized safely in patients
diagnosed with DCIS.
PMID- 27488121
TI - Resveratrol primes the effects of physical activity in old mice.
AB - Decrease in muscle mass and performance with ageing is one of the main factors of
frailty in the elderly. Maintenance of muscle performance by involving in
physical activities is essential to increase independence and quality of life
among elderly. The use of natural compounds with ergogenic activity in old people
would increase the effect of moderate exercises in the maintenance of
physiological muscle capacity. Resveratrol (RSV), a polyphenol found in walnuts,
berries and grapes, shows this ergogenic activity. By using young, mature and old
mice as models, we have found that RSV improves muscle performance in mature and
old animals but not in young animals. Without showing significant effect by
itself, RSV primed the effect of exercise by increasing endurance, coordination
and strength in old animals. This effect was accompanied by a higher protection
against oxidative damage and an increase in mitochondrial mass. RSV increased
catalase and superoxide dismutase protein levels in muscle and primed exercise to
reverse the decrease in their activities during ageing. Furthermore, RSV
increased the level of mitochondrial mass markers such as cytochrome C,
mitochondrial transcription factor A and nuclear respiratory factor-1 in muscle
in exercised animals. Our results indicate that RSV can be considered an
ergogenic compound that helps maintain muscle performance during ageing and
subsequently reduces frailty and increases muscle performance in old individuals
practising moderate exercise.
PMID- 27488122
TI - The circadian clock regulates inflammatory arthritis.
AB - There is strong diurnal variation in the symptoms and severity of chronic
inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of
the circadian clock is an aggravating factor associated with a range of human
inflammatory diseases. To investigate mechanistic links between the biological
clock and pathways underlying inflammatory arthritis, mice were administered
collagen (or saline as a control) to induce arthritis. The treatment provoked an
inflammatory response within the limbs, which showed robust daily variation in
paw swelling and inflammatory cytokine expression. Inflammatory markers were
significantly repressed during the dark phase. Further work demonstrated an
active molecular clock within the inflamed limbs and highlighted the resident
inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of
the rhythmic inflammatory signal. Exposure of mice to constant light disrupted
the clock in peripheral tissues, causing loss of the nighttime repression of
local inflammation. Finally, the results show that the core clock proteins
cryptochrome (CRY) 1 and 2 repressed inflammation within the FLSs, and provide
novel evidence that a CRY activator has anti-inflammatory properties in human
cells. We conclude that under chronic inflammatory conditions, the clock actively
represses inflammatory pathways during the dark phase. This interaction has
exciting potential as a therapeutic avenue for treatment of inflammatory disease.
Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I.,
Ray, D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates
inflammatory arthritis.
PMID- 27488124
TI - Interventions to improve hospital patient satisfaction with healthcare providers
and systems: a systematic review.
AB - BACKGROUND: Many hospital systems seek to improve patient satisfaction as
assessed by the Hospital Consumer Assessment of Healthcare Providers and Systems
(HCAHPS) surveys. A systematic review of the current experimental evidence could
inform these efforts and does not yet exist. METHODS: We conducted a systematic
review of the literature by searching electronic databases, including MEDLINE and
EMBASE, the six databases of the Cochrane Library and grey literature databases.
We included studies involving hospital patients with interventions targeting at
least 1 of the 11 HCAHPS domains, and that met our quality filter score on the 27
item Downs and Black coding scale. We calculated post hoc power when appropriate.
RESULTS: A total of 59 studies met inclusion criteria, out of these 44 did not
meet the quality filter of 50% (average quality rating 27.8%+/-10.9%). Of the 15
studies that met the quality filter (average quality rating 67.3%+/-10.7%), 8
targeted the Communication with Doctors HCAHPS domain, 6 targeted Overall
Hospital Rating, 5 targeted Communication with Nurses, 5 targeted Pain
Management, 5 targeted Communication about Medicines, 5 targeted Recommend the
Hospital, 3 targeted Quietness of the Hospital Environment, 3 targeted
Cleanliness of the Hospital Environment and 3 targeted Discharge Information.
Significant HCAHPS improvements were reported by eight interventions, but their
generalisability may be limited by narrowly focused patient populations,
heterogeneity of approach and other methodological concerns. CONCLUSIONS:
Although there are a few studies that show some improvement in HCAHPS score
through various interventions, we conclude that more rigorous research is needed
to identify effective and generalisable interventions to improve patient
satisfaction.
PMID- 27488123
TI - Motor neuron mitochondrial dysfunction in spinal muscular atrophy.
AB - Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality,
predominantly affects high metabolic tissues including motor neurons, skeletal
muscles and the heart. Although the genetic cause of SMA has been identified,
mechanisms underlying tissue-specific vulnerability are not well understood. To
study these mechanisms, we carried out a deep sequencing analysis of the
transcriptome of spinal motor neurons in an SMA mouse model, in which we
unexpectedly found changes in many genes associated with mitochondrial
bioenergetics. Importantly, functional measurement of mitochondrial activities
showed decreased basal and maximal mitochondrial respiration in motor neurons
from SMA mice. Using a reduction-oxidation sensitive GFP and fluorescence sensors
specifically targeted to mitochondria, we found increased oxidative stress level
and impaired mitochondrial membrane potential in motor neurons affected by SMA.
In addition, mitochondrial mobility was impaired in SMA disease conditions, with
decreased retrograde transport but no effect on anterograde transport. We also
found significantly increased fragmentation of the mitochondrial network in
primary motor neurons from SMA mice, with no change in mitochondria density.
Electron microscopy study of SMA mouse spinal cord revealed mitochondria
fragmentation, edema and concentric lamellar inclusions in motor neurons affected
by the disease. Intriguingly, these functional and structural deficiencies in the
SMA mouse model occur during the presymptomatic stage of disease, suggesting a
role in initiating SMA. Altogether, our findings reveal a critical role for
mitochondrial defects in SMA pathogenesis and suggest a novel target for
improving tissue health in the disease.
PMID- 27488125
TI - Tavaborole, Efinaconazole, and Luliconazole: Three New Antimycotic Agents for the
Treatment of Dermatophytic Fungi.
AB - Fungal diseases of the nail bed (onychomycosis) and epidermis are recurrent
illnesses in the elderly and immunocompromised patients, which have few
efficacious treatment options. Current treatment options for onychomycosis are
limited to topical agents, laser treatment, and oral antifungals. Previous
generations of topical agents were not efficacious, owing to poor penetration of
the nail bed. Oral antifungal drugs, such as itraconazole, terbinafine, and
fluconazole, not only give better response rates but also inhibit a host of
CYP450 enzymes. Oral antifungals can exacerbate drug-drug interactions for
patients taking other medications concurrently. Newer topical agents might
recognize improved efficacy and provide therapeutic alternatives when the use of
oral antifungal agents is contraindicated. Recently, the Food and Drug
Administration (FDA) approved efinaconazole and tavaborole for the treatment of
onychomycosis. Additionally, the FDA approved luliconazole for the treatment of
tinea pedis, tinea cruris, and tinea corporis. This review examines the mechanism
of action, spectrum of activity, pharmacokinetics, and clinical trials data and
considers the place in therapy for these 3 new antimycotic agents.
PMID- 27488126
TI - Walking towards personalized medicine in pulmonary rehabilitation: Comorbidities
and COPD.
PMID- 27488127
TI - Aspects of skeletal muscles in chronic respiratory disease.
PMID- 27488128
TI - MR Parametric Mapping as a Biomarker of Early Joint Degeneration.
AB - CONTEXT: Osteoarthritis (OA) is a common, worldwide disorder. Magnetic resonance
(MR) imaging can directly and noninvasively evaluate articular cartilage and has
emerged as an essential tool in the study of OA. EVIDENCE ACQUISITION: A PubMed
search was performed using the keywords quantitative MRI and cartilage. No limits
were set on the range of years searched. Articles were reviewed for relevance
with an emphasis on in vivo studies performed at 3 tesla. STUDY DESIGN: Clinical
review. LEVEL OF EVIDENCE: Level 4. RESULTS: T2, T2*, T1 (particularly when
measured after exogenous contrast administration, such as with the delayed
gadolinium-enhanced MR imaging of cartilage [dGEMRIC] technique), and T1rho are
among the most widely utilized quantitative MR imaging techniques to evaluate
cartilage and have been implemented in various patient cohorts. Existing
challenges include reproducibility of results, insufficient consensus regarding
optimal sequences and parameters, and interpretation of values. CONCLUSION:
Quantitative assessment of cartilage using MR imaging techniques likely
represents the best opportunity to identify early cartilage degeneration and to
follow patients after treatment. Despite existing challenges, ongoing work and
unique approaches have shown exciting and promising results.
PMID- 27488130
TI - Advances in the Physiology of GPR55 in the Central Nervous System.
AB - BACKGROUND: The G protein-coupled receptor 55 (GPR55) is a mammalian orphan
receptor that awaits a formal classification. There are an increasing number of
reports directed to know the physiology and pathophysiology of this receptor.
Lamentably, its functions in the central nervous system (CNS) have been scarcely
elucidated. METHODS: A bibliographic search in PubMed database about GPR55
actions in the CNS was made. The information was grouped for brain structures to
facilitate the interpretation. Finally, we constructed a schematic representation
of the current knowledge about the potential participation of GPR55 in some
physiological and pathophysiological events. RESULTS: Seventy nine papers were
included in the review. Only few of them showed data about GPR55 (mRNA/protein)
expression in multiple brain areas. The rest showed findings in different
preparations both in vitro and in vivo conditions that allowed us to speculate a
potential activity of GPR55 in the different brain areas. CONCLUSION: GPR55 mRNA
is expressed in several brain areas as the hippocampus, hypothalamus, frontal
cortex and cerebellum; but due to the lack of information, only some speculative
information about its function in these regions has been suggested. Therefore,
this review provide relevant information to motivate further research about GPR55
physiology/pathophysiology in the CNS.
PMID- 27488131
TI - Penicillin binding protein 3 of Staphylococcus aureus NCTC 8325-4 binds and
activates human plasminogen.
AB - BACKGROUND: Staphylococcus aureus is a versatile pathogen expressing a number of
virulence-associated adhesive molecules. In a previous study, we generated in a
secretion-competent Escherichia coli strain a library of random FLAG-tag positive
(FTP) polypeptides of S. aureus. To identify adhesive proteins and gain
additional knowledge on putative virulence factors of S. aureus, we here screened
the FTP library against human serum proteins. FINDINGS: Staphylococcus aureus
NCTC 8325-4, origin of the FTP library, adhered to immobilized plasminogen in
vitro. In an enzyme-linked immunoassay a C-terminal part of penicillin binding
protein 3 (PBP3), included in the FTP library, bound to immobilized plasminogen.
We expressed and purified full-length PBP3 and its C-terminal fragments as
recombinant proteins. In a time-resolved fluorometry-based assay the PBP3
polypeptides bound to immobilized plasminogen. The polypeptides enhanced
formation of plasmin from plasminogen as analyzed by cleavage of a chromogenic
plasmin substrate. CONCLUSIONS: The present findings, although preliminary,
demonstrate reliably that S. aureus NCTC 8325-4 adheres to immobilized
plasminogen in vitro and that the adhesion may be mediated by a C-terminal
fragment of the PBP3 protein. The full length PBP3 and the penicillin binding C
terminal domain of PBP3 expressed as recombinant proteins bound plasminogen and
activated plasminogen to plasmin. These phenomena were inhibited by the lysine
analogue epsilon-aminocaproic acid suggesting that the binding is mediated by
lysine residues. A detailed molecular description of surface molecules enhancing
the virulence of S. aureus will aid in understanding of its pathogenicity and
help in design of antibacterial drugs in the future.
PMID- 27488132
TI - Correction: In vivo 808 nm image-guided photodynamic therapy based on an
upconversion theranostic nanoplatform.
AB - Correction for 'In vivo 808 nm image-guided photodynamic therapy based on an
upconversion theranostic nanoplatform' by Xiaomin Liu, et al., Nanoscale, 2015,
7, 14914-14923.
PMID- 27488135
TI - Second sphere coordination of hybrid metal-organic materials: solid state
reactivity.
AB - When compared to other hybrid metal organic materials such as metal-organic
frameworks, hydrogen bonded materials self-assembled by metals and organic
molecules using second sphere interactions have been poorly investigated.
Consequently, their solid-sate properties are also scarce. In this perspective,
earlier research mainly on host-guest chemistry and its evolution towards more
extended structures by applying crystal engineering principles using second
sphere coordination is described. Crystal-to-crystal guest exchange reactions,
permanently porous hybrid metal organic materials, mechanochemical reactivity,
thermally induced phase transformations as well as some examples of functional
technological applications using second sphere adducts such as gas adsorption,
separation and non-linear optical phenomena are also reported. Although some
tutorial reviews on second sphere adducts have been conducted mainly in the
solution state focusing on metal based anion receptors, to the best of our
knowledge, an overview on relevant works that focus on the solid-state properties
has not been carried out. The aim of this article is to highlight from some of
the early fundamental work to the latest reports on hybrid metal-organic
materials self-assembled via second sphere interactions with a focus on solid
state chemistry.
PMID- 27488134
TI - Australian human and parrot Chlamydia psittaci strains cluster within the highly
virulent 6BC clade of this important zoonotic pathogen.
AB - Chlamydia psittaci is an avian pathogen and zoonotic agent of atypical pneumonia.
The most pathogenic C. psittaci strains cluster into the 6BC clade, predicted to
have recently emerged globally. Exposure to infected parrots is a risk factor
with limited evidence also of an indirect exposure risk. Genome sequencing was
performed on six Australian human and a single avian C. psittaci strain isolated
over a 9 year period. Only one of the five human patients had explicit psittacine
contact. Genomics analyses revealed that the Australian C. psittaci strains are
remarkably similar, clustering tightly within the C. psittaci 6BC clade suggested
to have been disseminated by South America parrot importation. Molecular clock
analysis using the newly sequenced C. psittaci genomes predicted the emergence of
the 6BC clade occurring approximately 2,000 years ago. These findings reveal the
potential for an Australian natural reservoir of C. psittaci 6BC strains. These
strains can also be isolated from seriously ill patients without explicit
psittacine contact. The apparent recent and global spread of C. psittaci 6BC
strains raises important questions over how this happened. Further studies may
reveal whether the dissemination of this important zoonotic pathogen is linked to
Australian parrot importation rather than parrots from elsewhere.
PMID- 27488133
TI - Skeletal complications in cancer patients with bone metastases.
AB - As a result of significant improvements in current therapies, the life expectancy
of cancer patients with bone metastases has dramatically improved. Unfortunately,
these patients often experience skeletal complications that significantly impair
their quality of life. The major skeletal complications associated with bone
metastases include: cancer-induced bone pain, hypercalcemia, pathological bone
fractures, metastatic epidural spinal cord compression and cancer cachexia. Once
cancer cells invade the bone, they perturb the normal physiology of the marrow
microenvironment, resulting in bone destruction, which is believed to be a direct
cause of skeletal complications. However, full understanding of the mechanisms
responsible for these complications remains unknown. In the present review, we
discuss the complications associated with bone metastases along with matched
conventional therapeutic strategies. A better understanding of this topic is
crucial, as targeting skeletal complications can improve both the morbidity and
mortality of patients suffering from bone metastases.
PMID- 27488136
TI - Using thermal desorption electrospray ionization mass spectrometry to rapidly
determine antimicrobial preservatives in cosmetics.
AB - RATIONALE: Characterization and quantification of permitted preservatives are
important inspections to prevent the overuse of preservatives in authentic
formulations. However, the complexity of sample matrices makes preservative
determination in cosmetics a tedious process. A rapid analytical strategy to
identify preservatives would insure large numbers of products are in compliance
with government regulations. METHODS: Thermal desorption electrospray ionization
mass spectrometry (TD-ESI-MS) was used to directly detect preservative compounds
in authentic formulations without sample pretreatment. The technique employs a
metal probe, which was configured for sampling cosmetics in their original states
and was inserted in a closed preheated oven to thermally desorb analytes. The
desorbed analytes were then carried by a nitrogen gas stream into an ESI plume,
where the formed ions were subsequently detected by the mass analyzer. RESULTS:
The TD-ESI mass and tandem mass spectra of different classes of preservative
standards were rapidly obtained, and the limits of detection were far below the
legal limit of their respective concentrations. The preservatives were also
directly detected in different types of authentic formulations in the absence of
sample preparation, and within a few seconds per sample. Calibration curves for
preservatives in four common formulations yielded good linearity in the
regulation-allowed range. CONCLUSIONS: Due to its sensitivity, short analysis
time, repeatability, and quantitative ability, TD-ESI-MS may serve as a suitable
tool for large-scale screening of cosmetic preservatives to assure product
safety. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27488137
TI - "Water-in-salt" electrolytes enable the use of cost-effective aluminum current
collectors for aqueous high-voltage batteries.
AB - The extended electrochemical stability window offered by highly concentrated
electrolytes allows the operation of aqueous batteries at voltages significantly
above the thermodynamic stability limit of water, at which the stability of the
current collector potentially limits the cell voltage. Here we report the
observation of suppressed anodic dissolution of aluminum in "water-in-salt"
electrolytes enabling roll-to-roll electrode fabrication for high-voltage aqueous
lithium-ion batteries on cost-effective light-weight aluminum current collectors
using established lithium-ion battery technology.
PMID- 27488138
TI - Draft genome of an iconic Red Sea reef fish, the blacktail butterflyfish
(Chaetodon austriacus): current status and its characteristics.
AB - Butterflyfish are among the most iconic of the coral reef fishes and represent a
model system to study general questions of biogeography, evolution and population
genetics. We assembled and annotated the genome sequence of the blacktail
butterflyfish (Chaetodon austriacus), an Arabian region endemic species that is
reliant on coral reefs for food and shelter. Using available bony fish
(superclass Osteichthyes) genomes as a reference, a total of 28 926 high-quality
protein-coding genes were predicted from 13 967 assembled scaffolds. The quality
and completeness of the draft genome of C. austriacus suggest that it has the
potential to serve as a resource for studies on the co-evolution of reef fish
adaptations to the unique Red Sea environment, as well as a comparison of gene
sequences between closely related congeneric species of butterflyfish distributed
more broadly across the tropical Indo-Pacific.
PMID- 27488140
TI - Following a potential epileptogenic insult, prolonged high rates of nonlinear
dynamical regimes of intermittency type is the hallmark of epileptogenesis.
AB - The lack of a marker of epileptogenesis is an unmet medical need, not only from
the clinical perspective but also from the point of view of the pre-clinical
research. Indeed, the lack of this kind of marker affects the investigations on
the mechanisms of epileptogenesis as well as the development of novel therapeutic
approaches aimed to prevent or to mitigate the severity of the incoming epilepsy
in humans. In this work, we provide evidence that in an experimental model of
epileptogenesis that mimics the alteration of the blood-brain barrier
permeability, a key-mechanism that contributes to the development of epilepsy in
humans and in animals, the prolonged occurrence in the electrocorticograms (ECoG)
of high rates of a nonlinear dynamical regimes known as intermittency univocally
characterizes the population of experimental animals which develop epilepsy,
hence it can be considered as the first biophysical marker of epileptogenesis.
PMID- 27488141
TI - Gaps in Research on Adverse Events to Transfusion in Pediatrics.
AB - Adverse consequences of blood transfusion in children are not completely
understood. Much remains to be learned about defining their mechanisms, learning
how they can be avoided, and improving our understanding how to minimize the
morbidity of their consequences. All types of transfusion reactions can occur in
children. This article focuses on four adverse consequences that have particular
relevance for pediatric populations: cytomegalovirus transmission, red blood cell
alloimmunization, immune altering consequences of transfusion, and necrotizing
enterocolitis.
PMID- 27488142
TI - Combining web-based tools for transparent evaluation of data for risk assessment:
developmental effects of bisphenol A on the mammary gland as a case study.
AB - Different tools have been developed that facilitate systematic and transparent
evaluation and handling of toxicity data in the risk assessment process. The
present paper sets out to explore the combined use of two web-based tools for
study evaluation and identification of reliable data relevant to health risk
assessment. For this purpose, a case study was performed using in vivo toxicity
studies investigating low-dose effects of bisphenol A on mammary gland
development. The reliability of the mammary gland studies was evaluated using the
Science in Risk Assessment and Policy (SciRAP) criteria for toxicity studies. The
Health Assessment Workspace Collaborative (HAWC) was used for characterizing and
visualizing the mammary gland data in terms of type of effects investigated and
reported, and the distribution of these effects within the dose interval. It was
then investigated whether there was any relationship between study reliability
and the type of effects reported and/or their distribution in the dose interval.
The combination of the SciRAP and HAWC tools allowed for transparent evaluation
and visualization of the studies investigating developmental effects of BPA on
the mammary gland. The use of these tools showed that there were no apparent
differences in the type of effects and their distribution in the dose interval
between the five studies assessed as most reliable and the whole data set.
Combining the SciRAP and HAWC tools was found to be a useful approach for
evaluating in vivo toxicity studies and identifying reliable and sensitive
information relevant to regulatory risk assessment of chemicals. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27488143
TI - Prothrombin complex concentrates versus fresh frozen plasma for warfarin
reversal. A systematic review and meta-analysis.
AB - Urgent reversal of warfarin is required for patients who experience major
bleeding or require urgent surgery. Treatment options include the combination of
vitamin K and coagulation factor replacement with either prothrombin complex
concentrate (PCC) or fresh frozen plasma (FFP). However, the optimal reversal
strategy is unclear based on clinically relevant outcomes. We searched in
MEDLINE, EMBASE and Cochrane library to December 2015. Thirteen studies (5
randomised studies and 8 observational studies) were included. PCC use was
associated with a significant reduction in all-cause mortality compared to FFP
(OR= 0.56, 95 % CI; 0.37-0.84, p=0.006). A higher proportion of patients
receiving PCC achieved haemostasis compared to those receiving FFP, but this was
not statistically significant (OR 2.00, 95 % CI; 0.85-4.68). PCC use was more
likely to achieve normalisation of international normalised ratio (INR) (OR
10.80, 95 % CI; 6.12-19.07) and resulted in a shorter time to INR correction
(mean difference -6.50 hours, 95 %CI; -9.75 to -3.24). Red blood cell transfusion
was not statistically different between the two groups (OR 0.88, 95 % CI: 0.53
1.43). Patients receiving PCC had a lower risk of post-transfusion volume
overload compared to FFP (OR 0.27, 95 % CI; 0.13-0.58). There was no
statistically significant difference in the risk of thromboembolism following
administration of PCC or FFP (OR 0.91, 95 % CI; 0.44-1.89). In conclusion, as
compared to FFP, the use of PCC for warfarin reversal was associated with a
significant reduction in all-cause mortality, more rapid INR reduction, and less
volume overload without an increased risk of thromboembolic events.
PMID- 27488144
TI - Silacyclopropylideneplatinum(0) Complex as a Robust and Efficient Hydrosilylation
Catalyst.
AB - The base-stabilized silacyclopropylidene 1 behaves as a versatile strongly
nucleophilic ligand toward transition metals. The strong silylene-metal binding
related to both increased sigma-donating and pi-accepting character of silylene 1
compared to N-heterocyclic carbenes (NHCs) allowed the synthesis of robust and
air-stable silylene complexes. Of particular interest, the corresponding
platinum(0) complex 6 exhibits high stability and a high level of selectivity and
catalytic activity in hydrosilylation reactions that is superior to that of the
related NHC-Pt(0) complexes.
PMID- 27488145
TI - Yellow Neointima Following Stent Implantation in the Superficial Femoral Artery
on Angioscopy.
PMID- 27488146
TI - Interaction Between Brain and Heart.
PMID- 27488147
TI - Is ophthalmology becoming a pain in the neck?
PMID- 27488148
TI - Biopsy techniques for intraocular tumors.
AB - Biopsy involves the surgical removal of a tissue specimen for histopathologic
evaluation. Most intraocular tumors are reliably diagnosed based on the clinical
evaluation or with noninvasive diagnostic techniques. However, accurately
diagnosing a small percentage of tumors can be challenging. A tissue biopsy is
thus needed to establish a definitive diagnosis and plan the requisite treatment.
From fine-needle aspiration biopsy (FNAB) to surgical excision, all tissue
collection techniques have been studied in the literature. Each technique has its
indications and limitations. FNAB has been reported to provide for 88-95%
reliable and safe ophthalmic tumor diagnosis and has gained popularity for
prognostic purposes and providing eye conserving treatment surgeries. The
technique and instrumentation for biopsy vary depending upon the tissue involved
(retina, choroid, subretinal space, vitreous, and aqueous), suspected diagnosis,
size, location, associated retinal detachment, and clarity of the media. The
cytopathologist confers a very important role in diagnosis and their assistance
plays a key role in managing and planning the treatment for malignancies.
PMID- 27488149
TI - Clinical profile of medicolegal cases presenting to the eye casualty in a
tertiary care center in India.
AB - PURPOSE: The purpose of this study was to analyze the clinical profile of
medicolegal cases (MLCs) presenting to the eye casualty in a tertiary care
hospital. MATERIALS AND METHODS: Retrospective review of records. The cases were
grouped according to the Ocular Trauma Classification Group classification
system. RESULTS: Out of 188 MLCs, 164 (87.2%) were male. Mean age (+/-standard
deviation) was 31.6 (+/-12.7) years. Age ranged from 7 to 75 years. Twenty-six
(13.8%) patients had bilateral involvement. The fist was the most common mode of
injury, which was seen in 109 (58%) cases. A total of 27 (14.3%) patients had
associated extraocular injury. No evidence of ocular or orbital trauma
(malingering) could be found in 13 (7%) patients. Mechanical trauma was present
in 169 (90%) patients with injury to globe in 129 (69%) patients and injury to
lid or orbit without damage to the globe in 40 (21%) patients. Chemical injury
was observed in 6 (3%) patients. Closed globe injury (CGI) was seen in 116 eyes
and open globe injury (OGI) was noted in 29 eyes. The most common type of injury,
zone, pupil, and grade of injury in CGI were Type A or contusion (79%), Zone I
(72%), Pupil B (absence of relative afferent pupillary defect) in 95%, and Grade
A [visual acuity (VA) >=20/40] in 68% of the eyes, respectively. The most common
type of injury, zone, pupil, and grade of injury in OGI were Type B or
penetrating (48%), Zone II (38%), Pupil B (59%), and Grade D (VA 4/200-light
perception) (42%), respectively. CONCLUSIONS: The most common form and mode of
ocular injury in MLC were closed globe injury and fist, respectively. The most
common type of injury in CGI and OGI was contusion and penetrating injury,
respectively.
PMID- 27488150
TI - Change of retinal pigment epithelial atrophy after anti-vascular endothelial
growth factor treatment in exudative age-related macular degeneration.
AB - PURPOSE: The study aimed to investigate the quantitative changes of retinal
pigment epithelial (RPE) atrophy during a 24-month follow-up period of anti
vascular endothelial growth factor (VEGF) for exudative age-related macular
degeneration (AMD). MATERIALS AND METHODS: This is a retrospective study. Sixty
five eyes of 62 consecutive patients with naomicronve exudative AMD who had
received treatment with anti-VEGF therapy and followed for more 24 months were
enrolled. All patients received three initial monthly injections of anti-VEGF
(ranibizumab or bevacizumab), followed by pro re nata or treat-and-extend
protocol. Color fundus image, optical coherence tomography, and fundus
autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was
performed to investigate the predictive factors found during univariate analysis
to identify an association with increased RPE atrophic areas. RESULTS: The mean
number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 +/- 1.298 mm
2 at baseline and enlarged to 2.394 +/- 1.940 mm 2 after 24 months, which
differed significantly (P = 0.001). Multiple regression analysis revealed that
larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments
were associated with increased RPE atrophic areas. CONCLUSIONS: RPE atrophy
progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of
RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated
with an increased risk of progression of RPE atrophy the following treatment.
These findings may be useful to clinicians using intravitreal anti-VEGF for the
treatment of exudative AMD, both for selecting an appropriate treatment plan and
for predicting the progression of RPE atrophy.
PMID- 27488151
TI - Effect of thiamine pyrophosphate on retinopathy induced by hyperglycemia in rats:
A biochemical and pathological evaluation.
AB - PURPOSE: Information is lacking on the protective effects of thiamine
pyrophosphate (TPP) against hyperglycemia-induced retinopathy in rats. This study
investigated the biochemical and histopathological aspects of the effect of TPP
on hyperglycemia-induced retinopathy induced by alloxan in rats. MATERIALS AND
METHODS: The rats were separated into a diabetic TPP-administered group (DTPG), a
diabetes control group (DCG) and a healthy group (HG). While the DTPG was given
TPP, the DCG and HG were administered distilled water as a solvent at the same
concentrations. This procedure was repeated daily for 3 months. At the end of
this period, all of the rats were euthanized under thiopental sodium anesthesia,
and biochemical and histopathological analyses of the ocular retinal tissues were
performed. The results of the DTPG were compared with those of the DCG and HG.
RESULTS: TPP prevented hyperglycemia by increasing the amount of malondialdehyde
and decreasing endogen antioxidants, including total glutathione, glutathione
reductase, glutathione S-transferase and superoxide dismutase. In addition, the
amounts of the DNA oxidation product 8-hydroxyguanine were significantly lower in
the retinas of the DTPG compared to the DCG. In the retinas of the DCG, there was
a marked increase in vascular structures and congestion, in addition to edema. In
contrast, little vascularization and edema were observed in the DTPG, and there
was no congestion. The results suggest that TPP significantly reduced the degree
of hyperglycemia-induced retinopathy. CONCLUSIONS: The results of this study
indicate that TPP may be useful for prophylaxis against diabetic retinopathy.
PMID- 27488152
TI - Failure to initiate early insulin therapy - A risk factor for diabetic
retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya
Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report
number 35).
AB - CONTEXT: Insulin users have been reported to have a higher incidence of diabetic
retinopathy (DR). AIM: The aim was to elucidate the factors associated with DR
among insulin users, especially association between duration, prior to initiating
insulin for Type 2 diabetes mellitus (DM) and developing DR. MATERIALS AND
METHODS: Retrospective cross-sectional observational study included 1414 subjects
having Type 2 DM. Insulin users were defined as subjects using insulin for
glycemic control, and insulin nonusers as those either not using any antidiabetic
treatment or using diet control or oral medications. The duration before
initiating insulin after diagnosis was calculated by subtracting the duration of
insulin usage from the duration of DM. DR was clinically graded using Klein's
classification. SPSS (version 9.0) was used for statistical analysis. RESULTS:
Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight
threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers.
Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence
interval [CI] 1.00-1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02
1.29, P = 0.021) was associated with DR. The presence of DR was significantly
associated with longer duration (>=5 years) prior to initiating insulin therapy,
overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic
control (32.5% vs. 67.5%, P = 0.022). CONCLUSIONS: The presence of DR is
significantly associated with longer duration of diabetes (>5 years) and sub
optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users,
abdominal obesity was found to be a significant predictor of DR; DR is associated
with longer duration prior to initiating insulin therapy in Type 2 DM subjects
with suboptimal glycemic control.
PMID- 27488153
TI - Preferences of ophthalmic plastics patients and their caregivers toward the
doctors' attire and initial communications: A tertiary eye care study.
AB - PURPOSE: The aims of this study were to determine the acceptability levels of
different styles of the doctors' dress and the expectations from the initial
phases of physician-patient encounter. METHODS: The study design was a cross
sectional descriptive type using the survey methodology. A survey based on a five
point questionnaire was performed on all consecutive patients or their
caregivers, aged >=15, visiting the ophthalmic plastics outpatient clinics at a
tertiary eye care institute. The participants were shown three sets of
photographs and were required to answer a questionnaire which consisted of five
questions. Data collected include participant demographics and their preferences
with regards to the physician's attire and initial communications. RESULTS: A
total of 300 consecutive responses were analyzed. The mean age of the
participants was 37.2 years. Among the participants, 87.6% (263/300) and 90.3%
(271/300) preferred a white coat for the male and female physicians, respectively
(P < 0.001). The most common second preference was scrubs for both the males and
female physicians. 92.3% (277/300) preferred the attire to have an identification
display. The overwhelming majority of respondents (95.6%, 287/300) preferred the
physicians to address them by their name and 98.6% (296/300) liked if their
physicians smiled while addressing them. CONCLUSIONS: White coat was the main
preferred attire among respondents. Increased awareness of the patient's
expectations plays a crucial role in enhancing their satisfaction.
PMID- 27488154
TI - Correlation between retinal sensitivity and cystoid space characteristics in
diabetic macular edema.
AB - PURPOSE: To evaluate the correlation between retinal sensitivity and cystoid
space characteristics in eyes with diabetic macular edema (DME). MATERIALS AND
METHODS: Prospective cross-sectional study of 22 subjects with DME (32 treatment
naive eyes). All study subjects underwent complete ophthalmic examination,
including slit-lamp biomicroscopy and dilated fundus examination. All subjects
underwent spectral domain optical coherence tomography (SD-OCT) and
microperimetry (MP). Intraretinal cystoid space (ICS) volume was generated after
manual delineation of cystoid space boundaries using the three-dimensional-OCT
software. Various SD-OCT parameters, including retinal thickness, retinal volume,
cystoid space volume, cystoid space intensity, and outer retinal structure
integrity, were correlated with MP parameters and best-corrected visual acuity
(BCVA). RESULTS: Subject's mean age was 57 +/- 9 years. The mean logarithm of
minimum angle of resolution BCVA was 0.4 +/- 0.2. The intraclass correlation
coefficient for inter- and intra-grader assessment of cystoid space volume by
manual delineation was 0.99 and 0.99, respectively. Mean total ICS volume was 0.4
+/- 0.4 mm 3 and for the foveal center, subfield was 0.1 +/- 0.1 mm 3 . Mean
retinal sensitivity was 12.89 +/- 10 dB; however, foveal retinal sensitivity was
12.3 +/- 11.1 dB. We found no significant correlation between BCVA and total
cystoid space volume (r = 0.33, P = 0.06). Correlation between total retinal
sensitivity and total ICS was negative and nonsignificant (r = -0.17, P = 0.36).
Correlation between foveal retinal sensitivity and foveal cystoid space intensity
was moderate and marginally significant (r = -0.43, P = 0.05). CONCLUSION: Total
cystoid space volume was not significantly correlated with BCVA or total retinal
sensitivity in subjects with DME. Foveal cystoid space optical intensity was
negatively correlated with foveal retinal sensitivity. These findings suggest
further investigation of cystoid space characteristics in the setting of DME may
be of value.
PMID- 27488155
TI - Prostaglandin-associated periorbitopathy.
PMID- 27488156
TI - Intralesional and topical interferon therapy following incomplete primary
excision of ocular surface squamous neoplasia.
PMID- 27488157
TI - First case report of isolated aspergillus dacryoadenitis.
AB - We report a case of isolated Aspergillus dacryoadenitis. A 23-year-old male
presented with dull ache, diffuse swelling in superolateral quadrant of the right
orbit and proptosis for 4 months. Ocular examination showed conjunctival
congestion, discharge in the fornix and palpable lacrimal gland (LG) mass.
Routine hematological investigations followed by computed tomography scan of
orbits were done. He did not respond to a course of systemic and topical
antibiotics. Lateral orbitotomy with extended lid crease incision was performed
with excision biopsy of LG. Abundant blackish material was found in the LG
intraoperatively. The specimen was sent for histopathological examination (HPE).
HPE report showed Aspergillus. Thorough ENT and systemic evaluation ruled out any
other site with the fungus. To the best of our knowledge, this is the first case
report of Aspergillus infection in LG.
PMID- 27488158
TI - Purtscher-like retinopathy: A rare complication of peribulbar anesthesia.
AB - Purtscher and Purtscher-like retinopathy is a distinctive retinal syndrome
characterized by ischemic retinal whitening in a peripapillary pattern. We report
a case of Purtscher-like retinopathy in a healthy 64-year-old man after a routine
peribulbar anesthetic injection for cataract surgery. Although peribulbar
anesthesia is considered to be a safer alternative to retrobulbar anesthesia, it
has been associated with unusual but grave complications including central
retinal artery occlusion.
PMID- 27488159
TI - Solid variant of orbital angioleiomyoma: An unusual tumor at an unusual site.
AB - We describe the clinicopathological features of a solid variant of orbital
angioleiomyoma. A review of clinical records, diagnostic, and radiographic
studies combined with histopathological evaluation with standard histochemical
staining and immunohistochemistry was conducted. A 22-year-old male patient
presented with a mass in the region of the left lacrimal gland that was gradually
increasing over the past 2 years. Radiological and clinical examinations showed
no signs suspicious of a malignancy and fine needle aspiration cytology was
inconclusive. Therefore, an excision biopsy was performed. On histopathological
examination, the picture was consistent with a benign spindle cell tumor.
Immunohistochemistry showed positivity for CD 34 and CD 31 (markers for vascular
endothelium). The tumor also showed positivity for smooth muscle actin and Ki-67
proliferative index was low. Angioleiomyomas are rarely encountered in the orbit
and has features seen in leiomyoma as well as some vascular tumor elements. In
most cases, surgical excision is usually curative.
PMID- 27488160
TI - Unilateral anterior persistent fetal vasculature in a child with blepharophimosis
ptosis-epicanthus inversus syndrome: A surgical challenge.
AB - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal
dominant genetic disease. It is clinically characterized by four major features;
blepharophimosis, ptosis, epicanthus inversus, and telecanthus. We report a case
of a 1-year-old female with BPES with unilateral anterior persistent fetal
vasculature (PFV). On examination, she was found to have all the clinical
features of BPES, along with calcified and partially absorbed cataract with
elongated ciliary processes in her left eye. B-scan of left eye showed attached
retina with no evidence of posterior PFV. Systemic examination was normal. She
underwent cataract surgery with primary posterior capsulotomy with intraocular
lens implantation under general anesthesia. Literature search did not reveal any
previous reports of unilateral anterior PFV and BPES. The clinical features,
other associations, and the difficulties in the surgical management of this
condition are discussed.
PMID- 27488161
TI - One Chinese case with benign reactive lymphoid hyperplasia of the uvea.
PMID- 27488162
TI - Response to: Bilateral lateral rectus myotoxicity after retrobulbar anesthesia.
PMID- 27488163
TI - Response to: Choroidal thickness changes after dynamic exercise as measured by
spectral-domain optical coherence tomography.
PMID- 27488164
TI - Comment to: Effect of lanosterol on human nuclei.
PMID- 27488165
TI - Authors' reply.
PMID- 27488166
TI - Comment to: Dual effect hypothesis of insulin analogs on diabetic retinopathy.
PMID- 27488167
TI - Author's reply.
PMID- 27488168
TI - Comment to: Iris-claw intraocular lens implantation: Anterior chamber versus
retropupillary implantation.
PMID- 27488169
TI - Authors' reply.
PMID- 27488170
TI - Effects of maltreatment and parental schizophrenia spectrum disorders on early
childhood social-emotional functioning: a population record linkage study.
AB - AIMS: Childhood maltreatment and a family history of a schizophrenia spectrum
disorder (SSD) are each associated with social-emotional dysfunction in
childhood. Both are also strong risk factors for adult SSDs, and social-emotional
dysfunction in childhood may be an antecedent of these disorders. We used data
from a large Australian population cohort to determine the independent and
moderating effects of maltreatment and parental SSDs on early childhood social
emotional functioning. METHODS: The New South Wales Child Development Study
combines intergenerational multi-agency data using record linkage methods.
Multiple measures of social-emotional functioning (social competency,
prosocial/helping behaviour, anxious/fearful behaviour; aggressive behaviour, and
hyperactivity/inattention) on 69 116 kindergarten children (age ~5 years) were
linked with government records of child maltreatment and parental presentations
to health services for SSD. Multivariable analyses investigated the association
between maltreatment and social-emotional functioning, adjusting for demographic
variables and parental SSD history, in the population sample and in sub-cohorts
exposed and not exposed to parental SSD history. We also examined the association
of parental SSD history and social-emotional functioning, adjusting for
demographic variables and maltreatment. RESULTS: Medium-sized associations were
identified between maltreatment and poor social competency, aggressive behaviour
and hyperactivity/inattention; small associations were revealed between
maltreatment and poor prosocial/helping and anxious/fearful behaviours. These
associations did not differ greatly when adjusted for parental SSD, and were
greater in magnitude among children with no history of parental SSD. Small
associations between parental SSD and poor social-emotional functioning remained
after adjusting for demographic variables and maltreatment. CONCLUSIONS:
Childhood maltreatment and history of parental SSD are associated independently
with poor early childhood social-emotional functioning, with the impact of
exposure to maltreatment on social-emotional functioning in early childhood of
greater magnitude than that observed for parental SSDs. The impact of
maltreatment was reduced in the context of parental SSDs. The influence of
parental SSDs on later outcomes of maltreated children may become more apparent
during adolescence and young adulthood when overt symptoms of SSD are likely to
emerge. Early intervention to strengthen childhood social-emotional functioning
might mitigate the impact of maltreatment, and potentially also avert future
psychopathology.
PMID- 27488171
TI - Expression of a Grapevine NAC Transcription Factor Gene Is Induced in Response to
Powdery Mildew Colonization in Salicylic Acid-Independent Manner.
AB - Tissue colonization by grape powdery mildew (PM) pathogen Erysiphe necator
(Schw.) Burr triggers a major remodeling of the transcriptome in the susceptible
grapevine Vitis vinifera L. While changes in the expression of many genes bear
the signature of salicylic acid (SA) mediated regulation, the breadth of PM
induced changes suggests the involvement of additional regulatory networks. To
explore PM-associated gene regulation mediated by other SA-independent systems,
we designed a microarray experiment to distinguish between transcriptome changes
induced by E. necator colonization and those triggered by elevated SA levels. We
found that the majority of genes responded to both SA and PM, but certain genes
were responsive to PM infection alone. Among them, we identified genes of
stilbene synthases, PR-10 proteins, and several transcription factors. The
microarray results demonstrated that the regulation of these genes is either
independent of SA, or dependent, but SA alone is insufficient to bring about
their regulation. We inserted the promoter-reporter fusion of a PM-responsive
transcription factor gene into a wild-type and two SA-signaling deficient
Arabidopsis lines and challenged the resulting transgenic plants with an
Arabidopsis-adapted PM pathogen. Our results provide experimental evidence that
this grape gene promoter is activated by the pathogen in a SA-independent manner.
PMID- 27488172
TI - Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and
low vitamin D serum concentration.
AB - BACKGROUND: The vascular type represents a very rare, yet the clinically most
fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to
arterial bleedings and the friable tissue and the altered coagulation contribute
to the challenge in treatment strategies. Until now there is little information
about clotting characteristics that might influence hemostasis decisively and
eventually worsen emergency situations. RESULTS: 22 vascular type EDS patients
were studied for hemoglobin, platelet volume and count, Quick and activated
partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease,
vitamin D and platelet aggregation by modern standard laboratory methods. Results
show a high prevalence of over 50 % for platelet aggregation disorders in
vascular type EDS patients, especially for collagen and epinephrine induced
tests, whereas the plasmatic cascade did not show any alterations. Additionally,
more than half of the tested subjects showed low vitamin D serum levels, which
might additionally affect vascular wall integrity. CONCLUSION: The presented data
underline the importance of detailed laboratory screening methods in vascular
type EDS patients in order to allow for targeted application of platelet
interacting substances that might be of decisive benefit in the emergency
setting.
PMID- 27488173
TI - Home blood pressure and cardiovascular risk in treated hypertensive patients: the
prognostic value of the first and second measurements and the difference between
them in the HONEST study.
AB - Hypertension guidelines recommend using the average of two home blood pressure
(HBP) measurements obtained on one occasion to monitor blood pressure. We studied
the prognostic value of the first and second measurements or their average value
during the follow-up period, as well as the relationships among the difference
between the first and second HBP measurements and the prognosis using data from
the HONEST (HBP measurement with Olmesartan-Naive patients to Establish Standard
Target blood pressure) study. During the mean 2.02 years follow-up, 280 patients
had cardiovascular events. Hazard ratios (HRs) for cardiovascular events for each
1 mm Hg increase in the first, second and averaged morning home systolic blood
pressure (MHSBP) were similar. Hazards were significantly higher in patients with
a large difference between the first and second MHSBP (DeltaMHSBP) of <-5 mm Hg
(HR: 2.12) or ?5 mm Hg (HR: 1.44) compared with those with a small DeltaMHSBP of
?-5 to <5 mm Hg using the Cox proportional hazards model adjusted for the
averaged MHSBP during the follow-up and other risk factors. Hazards in patients
with an averaged MHSBP ?145 mmHg and a small DeltaMHSBP (HR: 3.11), those with an
averaged MHSBP ?125 to <145 mm Hg and a large DeltaMHSBP (HR: 1.91) and those
with an averaged MHSBP ?145 mm Hg and a large DeltaMHSBP (HR: 4.63) were higher
compared with those with an averaged MHSBP <125 mm Hg and a small DeltaMHSBP. In
conclusion, the first, second and averaged MHSBP measurements have similar
prognostic values. Prognosis is worse for patients with a large DeltaMHSBP. In
clinical practice, it would be prudent to measure the HBP two times and use the
average HBP of two measurements obtained on one occasion with particular
attention to patients with a large DeltaMHSBP.
PMID- 27488174
TI - Bessel beams with spatial oscillating polarization.
AB - Bessel beams are widely used in optical metrology mainly because of their large
Rayleigh range (focal length). Radial/azimuthal polarization of such beams is of
interest in the fields of material processing, plasma absorption or
communication. In this paper an experimental set-up is presented, which generates
a Bessel-type vector beam with a spatial polarization, oscillating along the
optical axis, when propagating in free space. A first holographic axicon (HA) HA1
produces a normal, linearly polarized Bessel beam, which by a second HA2 is
converted into the spatial oscillating polarized beam. The theory is briefly
discussed, the set-up and the experimental results are presented in detail.
PMID- 27488175
TI - Multilayered materials based on biopolymers as drug delivery systems.
AB - INTRODUCTION: The design of efficient therapeutic delivery devices has become a
tremendously active area of research with a strong contribution from the layer-by
layer (LbL) technology. The application of this simple yet firmly established
technique for the design of drug reservoirs originates a multitude of
multilayered systems of tailored architecture and with a high level of control of
drug administration. Areas covered: This review will focus on the most recent and
original research on LbL assemblies based on biopolymers including
polysaccharides, polypeptides and proteins, with potential use in drug delivery.
Herein, drug reservoirs consisting of multilayered planar films and capsules will
be examined with emphasis on the ones benefiting from the non-cytotoxic and
biocompatible nature of biopolymers, which are suitable to load, protect and
release a high payload of toxic and fragile drugs. Expert opinion: The
combination of biopolymers with LbL technology has undergone extensive research,
still, there is a multitude of R&D opportunities for the design of smart drug
delivery systems with distinct multilayered morphologies, low immunological
response, non-invasive drug release devices, as well as the design of theranostic
systems combining diagnostics and therapeutic features. Further developments in
terms of scaling towards mass production in the pharmaceutical industry are
expected in the long-term.
PMID- 27488176
TI - Genetic determinants of warfarin maintenance dose and time in therapeutic
treatment range: a RE-LY genomics substudy.
AB - AIMS: We investigated associations between genetic variation in candidate genes
and on a genome-wide scale with warfarin maintenance dose, time in therapeutic
range (TTR), and risk of major bleeding. MATERIALS & METHODS: In total, 982
warfarin-treated patients from the RE-LY trial were studied. RESULTS: After
adjusting for SNPs in VKORC1 and CYP2C9, SNPs in DDHD1 (rs17126068) and NEDD4
(rs2288344) were associated with dose. Adding these SNPs and CYP4F2 (rs2108622)
to a base model increased R(2) by 2.9%. An SNP in ASPH (rs4379440) was associated
with TTR (-6.8% per minor allele). VKORC1 was associated with time less than INR
2.0. VKORC1 and CYP2C9 were associated with time more than INR 3.0, but not with
major bleeding. CONCLUSIONS: We identified two novel genes associated with
warfarin maintenance dose and one gene associated with TTR. These genes need to
be replicated in an independent cohort.
PMID- 27488177
TI - Pseudochaetosphaeronema ginkgonis sp. nov., an endophyte isolated from Ginkgo
biloba.
AB - An endophytic strain (designated as SYPF 7195T) was isolated from a branch of a
ginkgo tree in Liaoning province of China. Strain SYPF 7195T was characterized by
its grey to greyish-green aerial mycelium, velvety to floccose surface and
swelling near the septa. Phylogenetic analyses, which were inferred from the
internal transcribed spacer (ITS) and partial sequences of the LSU and SSU of the
rDNA and translation elongation factor 1-alpha (TEF1), showed that strain SYPF
7195T belonged to the genus Pseudochaetosphaeronema, and was distinct from all
other species with high bootstrap-supported values (92 %). Strain SYPF 7195T
constitutes a separate evolutionary clade with Pseudochaetosphaeronema larense
and Pseudochaetosphaeronema martinelli, with P. martinelli as its closest
phylogenetic neighbour. The nucleotide differences between strain SYPF 7195T and
P. martinelli were 71 substitutions in the ITS region. Strain SYPF 7195Tcould
also be distinguished from P. martinelli by a number of physiological
characteristics. Combined with morphology and molecular analyses, strain SYPF
7195T merits recognition as a representative of a novel species of the genus
Pseudochaetosphaeronema, for which the name Pseudochaetosphaeronemaginkgonis sp.
nov. is proposed. The type strain is CBS 140953T (=CGMCC 3.17865T=SYPF 7195T).
The Mycobank number is MB 816567.
PMID- 27488178
TI - How does HPV vaccination status relate to risk perceptions and intention to
participate in cervical screening? a survey study.
AB - BACKGROUND: Women in several countries will soon be covered by two preventive
programmes targeting cervical cancer: HPV vaccination and cervical screening. The
HPV vaccines are expected to prevent approximately 70 % of cervical cancers. It
has been speculated, that HPV vaccinated women will not attend screening because
they falsely think that the vaccine has eliminated their cervical cancer risk.
The aim of this study was to investigate the association between HPV vaccination
status and perceptions of cervical cancer risk; perceptions of vaccine effect;
and intention to participate in cervical screening. Furthermore, to investigate
associations between perceptions of cervical cancer risk and intention to
participate in cervical screening. METHODS: A random sample of Danish women from
the birth cohorts 1993-1995 was invited to complete a web-based questionnaire
concerning risk perceptions and intentions to participate in cervical screening.
Main outcomes were: perceived lifetime-risk of cervical cancer; perceived HPV
vaccine effect; and intention to participate in cervical screening. RESULTS: HPV
vaccinated women more often than unvaccinated women intended to participate in
screening: adjusted odds ratio (OR) for being HPV vaccinated when intending to
participate in screening of 3.89 (95 % CI: 2.50-6.06). HPV vaccinated women
perceived cervical cancer risk to be higher than unvaccinated women did: adjusted
OR of 0.11 (95 % CI: 0.03-0.39) and 0.51 (95 % CI: 0.33-0.78) for being HPV
vaccinated while having the lowest perception of risk (in two different pre
specified dichotomisations). HPV vaccinated women perceived the vaccine effect to
be larger than unvaccinated women did: adjusted OR of 0.31 (95 % CI: 0.18-0.51)
and 0.37 (95 % CI: 0.25-0.53) for being HPV vaccinated while having the lowest
perception of vaccine effect (in two different pre-specified dichotomisations).
There were no associations between perceived cervical cancer risk and intention
to participate in screening. CONCLUSIONS: HPV vaccinated women more often than
unvaccinated women intended to participate in screening and they perceived
cervical cancer risk to be higher and the vaccine effect to be larger than
unvaccinated women did. However, in our analyses, risk perceptions could not
explain screening intentions neither among vaccinated nor among unvaccinated
women.
PMID- 27488179
TI - Morphometric characterisation of pterygium associated with corneal stromal
scarring using high-resolution anterior segment optical coherence tomography.
AB - AIMS: To investigate the role of high-resolution anterior segment optical
coherence tomography (HR-ASOCT) in the assessment of pterygia. METHODS: Single
centre cross-sectional study. Patients with primary pterygium and/or pingueculae
were included. Clinical assessment included HR-ASOCT, colour photography,
keratometry followed by histology. Associations were tested between HR-ASOCT
features of the pterygium and the degree of corneal scarring and elastotic
degeneration, astigmatism and best-corrected visual acuity. RESULTS: 29 eyes of
26 patients with pterygium and 6 patients with pinguecula were included. Apical
anterior stromal scarring was found in 23 cases (79.3%) reaching a mean depth of
68.8+/-21.7 um (minimum: 33 um, maximum: 126 um). Increased stromal scarring and
subepithelial elastotic degenerative tissue was significantly associated with HR
ASOCT features of flat bridging of the corneoscleral transition zone (p<0.01)
reduced thickness of the pterygium head (p=0.01), and a greater degree of corneal
astigmatism (p=0.04). CONCLUSIONS: HR-ASOCT is a useful tool for the assessment
and monitoring of pterygia in clinical practice. Features associated with
increased stromal scarring and astigmatism are reduced thickness of the head of
the pterygium and flat bridging of the corneoscleral transition zone.
PMID- 27488180
TI - ABSSeq: a new RNA-Seq analysis method based on modelling absolute expression
differences.
AB - BACKGROUND: The recent advances in next generation sequencing technology have
made the sequencing of RNA (i.e., RNA-Seq) an extemely popular approach for gene
expression analysis. Identification of significant differential expression
represents a crucial initial step in these analyses, on which most subsequent
inferences of biological functions are built. Yet, for identification of these
subsequently analysed genes, most studies use an additional minimal threshold of
differential expression that is not captured by the applied statistical
procedures. RESULTS: Here we introduce a new analysis approach, ABSSeq, which
uses a negative binomal distribution to model absolute expression differences
between conditions, taking into account variations across genes and samples as
well as magnitude of differences. In comparison to alternative methods, ABSSeq
shows higher performance on controling type I error rate and at least a similar
ability to correctly identify differentially expressed genes. CONCLUSIONS: ABSSeq
specifically considers the overall magnitude of expression differences, which
enhances the power in detecting truly differentially expressed genes by reducing
false positives at both very low and high expression level. In addition, ABSSeq
offers to calculate shrinkage of fold change to facilitate gene ranking and
effective outlier detection.
PMID- 27488182
TI - Validation of a symphysis-fundal height chart developed for pregnancy complicated
by diabetes and hyperglycemia: an observational study.
AB - BACKGROUND: The present study validates a symphysis-fundal height chart (SFH
chart) for pregnant women with type 2 diabetes mellitus (DM2), gestational
diabetes mellitus (GDM) and mild gestational hyperglycemia (MGH) attending at the
Diabetes and Pregnancy Reference Service of the Botucatu Medical School, UNESP,
Brazil. METHODS: A cross-sectional study was carried out to evaluate the
performance of the specific FHC in predicting small (SGA) and large (LGA) for
gestational age newborns (NB). We evaluated 206 pregnant women with DM2, GDM or
MGH and their NB. The last symphysis-fundal height measure, taken at birth, was
used to determine the sensitivity index (Sens), specificity index (Spe), positive
prediction value (PPV), negative prediction value (NPV) and accuracy in
predicting SGA and LGA. The gold standard was the Lubchenco birth
weight/gestational age ratio evaluated at birth. RESULTS: The mothers showed
adequate glycemic control; 91.3 % of all pregnant women achieved HbA1c < 6,5 % in
the third trimester. The SFH-chart tested achieved 100 % of Sens and NPV in
predicting both SGA and LGA, with accuracy of 90.3 % (85.5; 93.6) and 91.8 %
(87.2; 94.8), respectively, for predicting SGA and LGA newborns. CONCLUSIONS: The
Basso SFH-chart showed high performance in predicting both SGA and LGA newborns
of DM-2, GDM and MGH mothers, with better performance than the national reference
SFH-chart. These findings support the internal validation of the Basso SFH-chart,
which may be implemented in the prenatal care of the Diabetes and Pregnancy
Reference Service-Botucatu Medical School/UNESP.
PMID- 27488181
TI - European COMPARative Effectiveness research on blended Depression treatment
versus treatment-as-usual (E-COMPARED): study protocol for a randomized
controlled, non-inferiority trial in eight European countries.
AB - BACKGROUND: Effective, accessible, and affordable depression treatment is of high
importance considering the large personal and economic burden of depression.
Internet-based treatment is considered a promising clinical and cost-effective
alternative to current routine depression treatment strategies such as face-to
face psychotherapy. However, it is not clear whether research findings translate
to routine clinical practice such as primary or specialized mental health care.
The E-COMPARED project aims to gain knowledge on the clinical and cost
effectiveness of blended depression treatment compared to treatment-as-usual in
routine care. METHODS/DESIGN: E-COMPARED will employ a pragmatic, multinational,
randomized controlled, non-inferiority trial in eight European countries. Adults
diagnosed with major depressive disorder (MDD) will be recruited in primary care
(Germany, Poland, Spain, Sweden, and the United Kingdom) or specialized mental
health care (France, The Netherlands, and Switzerland). Regular care for
depression is compared to "blended" service delivery combining mobile and
Internet technologies with face-to-face treatment in one treatment protocol.
Participants will be followed up at 3, 6, and 12 months after baseline to
determine clinical improvements in symptoms of depression (primary outcome:
Patient Health Questionnaire-9), remission of depression, and cost-effectiveness.
Main analyses will be conducted on the pooled data from the eight countries (n =
1200 in total, 150 participants in each country). DISCUSSION: The E-COMPARED
project will provide mental health care stakeholders with evidence-based
information and recommendations on the clinical and cost-effectiveness of blended
depression treatment. TRIAL REGISTRATION: France: ClinicalTrials.gov NCT02542891
. Registered on 4 September 2015; Germany: German Clinical Trials Register
DRKS00006866 . Registered on 2 December 2014; The Netherlands: Netherlands Trials
Register NTR4962 . Registered on 5 January 2015; Poland: ClinicalTrials.Gov
NCT02389660 . Registered on 18 February 2015; Spain: ClinicalTrials.gov
NCT02361684 . Registered on 8 January 2015; Sweden: ClinicalTrials.gov
NCT02449447 . Registered on 30 March 2015; Switzerland: ClinicalTrials.gov
NCT02410616 . Registered on 2 April 2015; United Kingdom: ISRCTN registry,
ISRCTN12388725 . Registered on 20 March 2015.
PMID- 27488183
TI - Platelet inhibitory effects of juices from Pachyrhizus erosus L. root and Psidium
guajava L. fruit: a randomized controlled trial in healthy volunteers.
AB - BACKGROUND: The purpose of this study is to investigate cardiovascular benefits
of juices obtained from two commonly consumed fruits in Thailand, Pachyrhizus
erosus, L. (yam bean) and Psidium guajava, L. (guava), by examining their acute
cardiovascular effects in healthy volunteers. Possible involvements of the
dietary nitrate on their effects were investigated as well. METHOD: Thirty
healthy volunteers were randomly divided into three groups of 10 subjects per
group and each group was allocated to drink 500 ml of freshly prepared yam bean
root juice, guava fruit juice, or water. Systemic nitrate and nitrite
concentrations, heart rate, systolic and diastolic blood pressure, serum K(+)
concentrations, ex vivo platelet aggregation, and plasma cGMP concentrations were
monitored at the baseline and at various time points after the intake of juices
or water. Data were compared by repeated measures ANOVA. RESULTS: Following the
ingestion of both yam bean root juice and guava fruit juice, collagen-induced but
not ADP-induced platelet aggregation was attenuated. Ingestion of yam bean root
juice increased systemic nitrate and nitrite concentrations whereby elevated
nitrite concentrations correlated with the extent of inhibiting collagen-induced
platelet aggregation. In addition, positive correlation between systemic nitrite
and plasma cGMP concentrations and negative correlation between plasma cGMP
concentrations and the extent of collagen-induced platelet aggregation were
revealed. Nevertheless, yam bean root juice reduced only diastolic blood pressure
while guava fruit juice reduced heart rate, systolic and diastolic blood
pressure. CONCLUSION: The present study has illustrated, for the first time,
acute inhibitory effects of yam bean root juice and guava fruit juice on ex vivo
collagen-induced platelet aggregation in healthy subjects. Dietary nitrate was
shown to underlie the effect of yam bean root juice but not that of guava fruit
juice. Following yam bean root juice ingestion, systemic nitrate apparently
converts to nitrite and further to NO which may attenuate platelet responses to
collagen stimulation. Cardiovascular benefits of juices from yam bean root and
guava fruit are noteworthy in term of the cardiovascular health-promoting
approach. TRIAL REGISTRATION: Randomized controlled trial TCTR20150228001 .
PMID- 27488184
TI - Erratum to: Involvement of DNMT 3B promotes epithelial-mesenchymal transition and
gene expression profile of invasive head and neck squamous cell carcinomas cell
lines.
PMID- 27488185
TI - Thickness-Dependent Binding Energy Shift in Few-Layer MoS2 Grown by Chemical
Vapor Deposition.
AB - The thickness-dependent surface states of MoS2 thin films grown by the chemical
vapor deposition process on the SiO2-Si substrates are investigated by X-ray
photoelectron spectroscopy. Raman and high-resolution transmission electron
microscopy suggest the thicknesses of MoS2 films to be ranging from 3 to 10
layers. Both the core levels and valence band edges of MoS2 shift downward ~0.2
eV as the film thickness increases, which can be ascribed to the Fermi level
variations resulting from the surface states and bulk defects. Grainy features
observed from the atomic force microscopy topographies, and sulfur-vacancy
induced defect states illustrated at the valence band spectra imply the
generation of surface states that causes the downward band bending at the n-type
MoS2 surface. Bulk defects in thick MoS2 may also influence the Fermi level
oppositely compared to the surface states. When Au contacts with our MoS2 thin
films, the Fermi level downshifts and the binding energy reduces due to the hole
doping characteristics of Au and easy charge transfer from the surface defect
sites of MoS2. The shift of the onset potentials in hydrogen evolution reaction
and the evolution of charge-transfer resistances extracted from the impedance
measurement also indicate the Fermi level varies with MoS2 film thickness. The
tunable Fermi level and the high chemical stability make our MoS2 a potential
catalyst. The observed thickness-dependent properties can also be applied to
other transition-metal dichalcogenides (TMDs), and facilitates the development in
the low-dimensional electronic devices and catalysts.
PMID- 27488186
TI - Nonmedical use of prescription drugs in the European Union.
AB - BACKGROUND: Nonmedical prescription drug use (NMPDU) refers to the self-treatment
of a medical condition using medication without a prescriber's authorization as
well as use to achieve euphoric states. This article reports data from a cross
national investigation of NMPDU in five European Countries, with the aim to
understand the prevalence and characteristics of those engaging in NMPDU across
the EU. METHODS: A parallel series of self-administered, cross-sectional, general
population surveys were conducted in 2014. Data were collected using multi-stage
quota sampling and then weighted using General Exponential Model. A total of
22,070 non-institutionalized participants, aged 12 to 49 years, in 5 countries:
Denmark, Germany, Great Britain, Spain, and Sweden. Lifetime and past-year
nonmedical use of prescription medications such as stimulants, opioids, and
sedatives were ascertained via a modified version of the World Health
Organization's Composite International Diagnostic Interview. Information about
how the medications were acquired for NMPDU were also collected from the
respondent. RESULTS: Lifetime and past-year prevalence of nonmedical prescription
drug use was estimated for opioids (13.5 and 5.0 %), sedatives (10.9 and 5.8 %),
and stimulants (7.0 and 2.8 %). Germany exhibited the lowest levels of NMPDU,
with Great Britain, Spain, and Sweden having the highest levels. Mental and
sexual health risk factors were associated with an increased likelihood of past
year nonmedical prescription drug use. Among past-year users, about 32, 28, and
52 % of opioid, sedative, and stimulant nonmedical users, respectively, also
consumed illicit drugs. Social sources (sharing by friends/family) were the most
commonly endorsed methods of acquisition, ranging from 44 % (opioids) to 62 %
(sedatives). Of interest is that Internet pharmacies were a common source of
medications for opioids (4.1 %), stimulants (7.6 %), and sedatives (2.7 %).
CONCLUSIONS: Nonmedical prescription drug use was reported across the five EU
countries we studied, with opioids and sedatives being the most prevalent classes
of prescription psychotherapeutics. International collaborations are needed for
continued monitoring and intervention efforts to target population subgroups at
greatest risk for NMDU.
PMID- 27488187
TI - Material hardship and children's social-emotional development: Testing mitigating
effects of Child Development Accounts in a randomized experiment.
AB - BACKGROUND: Research has established a negative association between household
material hardship and children's mental health. This study examines whether Child
Development Accounts (CDAs), an economic intervention that encourages families to
accumulate assets for children's long-term development, mitigate the association
between material hardship and children's social-emotional development. METHODS:
Researchers conducted a randomized experiment of CDAs in Oklahoma, USA, with a
probability sample (N = 7328) of all infants born in two 3-month periods in 2007.
After agreeing to participate in the experiment, caregivers of 2704 infants
completed a baseline survey and were assigned randomly to the treatment (n =
1358) or control group (n = 1346). The intervention exposed the treatment group
to a CDA, which consisted of an Oklahoma 529 College Savings Plan account,
financial incentives and financial information. RESULTS: Material hardship has a
negative association with the social-emotional development of children around the
age of 4 years. Estimates from regression analysis indicate that CDAs mitigate
about 50% of the negative association between material hardship and children's
social-emotional development. CONCLUSIONS: Although they do not provide direct
support for consumption in households experiencing material hardship, CDAs may
improve child development by influencing parenting practices and parents'
expectations for their children. We discuss the implications of using asset
building programmes to improve child development.
PMID- 27488188
TI - Dissecting relative contributions of cis- and trans-determinants to nucleosome
distribution by comparing Tetrahymena macronuclear and micronuclear chromatin.
AB - The ciliate protozoan Tetrahymena thermophila contains two types of structurally
and functionally differentiated nuclei: the transcriptionally active somatic
macronucleus (MAC) and the transcriptionally silent germ-line micronucleus (MIC).
Here, we demonstrate that MAC features well-positioned nucleosomes downstream of
transcription start sites and flanking splice sites. Transcription-associated
trans-determinants promote nucleosome positioning in MAC. By contrast,
nucleosomes in MIC are dramatically delocalized. Nucleosome occupancy in MAC and
MIC are nonetheless highly correlated with each other, as well as with in vitro
reconstitution and predictions based upon DNA sequence features, revealing
unexpectedly strong contributions from cis-determinants. In particular, well
positioned nucleosomes are often matched with GC content oscillations. As many
nucleosomes are coordinately accommodated by both cis- and trans-determinants, we
propose that their distribution is shaped by the impact of these nucleosomes on
the mutational and transcriptional landscape, and driven by evolutionary
selection.
PMID- 27488189
TI - Impact of donor-recipient phylogenetic distance on bacterial genome
transplantation.
AB - Genome transplantation (GT) allows the installation of purified chromosomes into
recipient cells, causing the resulting organisms to adopt the genotype and the
phenotype conferred by the donor cells. This key process remains a bottleneck in
synthetic biology, especially for genome engineering strategies of intractable
and economically important microbial species. So far, this process has only been
reported using two closely related bacteria, Mycoplasma mycoides subsp. capri
(Mmc) and Mycoplasma capricolum subsp. capricolum (Mcap), and the main factors
driving the compatibility between a donor genome and a recipient cell are poorly
understood. Here, we investigated the impact of the evolutionary distance between
donor and recipient species on the efficiency of GT. Using Mcap as the recipient
cell, we successfully transplanted the genome of six bacteria belonging to the
Spiroplasma phylogenetic group but including species of two distinct genera. Our
results demonstrate that GT efficiency is inversely correlated with the
phylogenetic distance between donor and recipient bacteria but also suggest that
other species-specific barriers to GT exist. This work constitutes an important
step toward understanding the cellular factors governing the GT process in order
to better define and eventually extend the existing genome compatibility limit.
PMID- 27488190
TI - Force and twist dependence of RepC nicking activity on torsionally-constrained
DNA molecules.
AB - Many bacterial plasmids replicate by an asymmetric rolling-circle mechanism that
requires sequence-specific recognition for initiation, nicking of one of the
template DNA strands and unwinding of the duplex prior to subsequent leading
strand DNA synthesis. Nicking is performed by a replication-initiation protein
(Rep) that directly binds to the plasmid double-stranded origin and remains
covalently bound to its substrate 5'-end via a phosphotyrosine linkage. It has
been proposed that the inverted DNA sequences at the nick site form a cruciform
structure that facilitates DNA cleavage. However, the role of Rep proteins in the
formation of this cruciform and the implication for its nicking and religation
functions is unclear. Here, we have used magnetic tweezers to directly measure
the DNA nicking and religation activities of RepC, the replication initiator
protein of plasmid pT181, in plasmid sized and torsionally-constrained linear DNA
molecules. Nicking by RepC occurred only in negatively supercoiled DNA and was
force- and twist-dependent. Comparison with a type IB topoisomerase in similar
experiments highlighted a relatively inefficient religation activity of RepC.
Based on the structural modeling of RepC and on our experimental evidence, we
propose a model where RepC nicking activity is passive and dependent upon the
supercoiling degree of the DNA substrate.
PMID- 27488191
TI - BMP and WNT: the road to cardiomyocytes is paved with precise modulation.
PMID- 27488192
TI - On-the-road driving performance after use of the antihistamines mequitazine and l
mequitazine, alone and with alcohol.
AB - OBJECTIVE: Previous studies demonstrated that mequitazine produces mild sedation
after single doses. Its enantiomer, l-mequitazine, has a stronger potency for the
H1 receptor. The aim of the current study was to assess the effects of l
mequitazine and mequitazine, alone and with alcohol, on driving. METHODS: Twenty
five healthy volunteers were treated with l-mequitazine 2.5, 5.0 and 10 mg,
mequitazine 10 mg and placebo, alone and in combination with alcohol in a double
blind crossover design. Driving performance was assessed using the standardized
highway driving test in normal traffic. Its primary measure is the Standard
Deviation of the Lateral Position (SDLP). Secondary measures consisted of an
auditory word learning test during driving, and subjective measures of driving
performance. RESULTS: L-mequitazine 2.5 and 5.0 mg showed no effect on SDLP in
the highway driving test, while SDLP significantly increased after l-mequitazine
10 mg (alone +1.59 cm; with alcohol +1.41 cm) and mequitazine 10 mg (with alcohol
+1.17 cm). Alcohol significantly impaired all performance measures (SDLP +2.63
cm) but did not interact with the effects of treatment. Subjective measures
indicated that participants were aware of the impairing effects of alcohol, but
not of l-mequitazine and mequitazine. CONCLUSION: L-mequitazine can be considered
safe to drive in dosages of 2.5 and 5.0 mg. L-mequitazine 10 mg led to mild
driving impairment. Alcohol impaired all performance measures and added to the
effects of l-mequitazine and mequitazine.
PMID- 27488194
TI - Cyto- and genotoxic potential of water samples from polluted areas in Kosovo.
AB - Reports on the state of the environment in Kosovo have emphasized that river and
ground water quality is affected by pollution from untreated urban water as well
as the waste water from the industry. One of the main contributors to this
pollution is located in Obiliq (coal power plants). Prishtina-the capital city of
Kosovo-is heavily influenced too. Furthermore, the pollutants combined together
with those from heavy traffic are dissolved in Prishtina runoff water, which is
discharged into the creek entering the river Sitnica together with urban waste
water. The available data show the complex pollution with excessive quantities of
nitrites, suspended materials, organic compounds, detergents, heavy metals,
polychlorinated biphenyls, etc. In this study, the cytotoxic and genotoxic
potential of water samples taken at these sites was tested in primary rat
hepatocytes. The results obtained indicate that water samples collected in
Prishtina and Obiliq had a significant cytotoxic potential in primary rat
hepatocyte cultures even when diluted to 1 %. The increased cytotoxicity,
however, was not accompanied by an increased genotoxicity as measured by the
percentage of micronucleated cells. Further investigations addressing the
chemical composition of the samples and the identification of the toxicants
responsible for the cytotoxic effects found will be carried out in a next step.
PMID- 27488193
TI - Comparison of R-ketamine and rapastinel antidepressant effects in the social
defeat stress model of depression.
AB - RATIONALE: The N-methyl-D-aspartate (NMDA) receptor antagonists, including R
ketamine and rapastinel (formerly GLYX-13), show rapid antidepressant effects in
animal models of depression. OBJECTIVE: We compared the rapid and sustained
antidepressant effects of R-ketamine and rapastinel in the social defeat stress
model. RESULTS: In the tail suspension and forced swimming tests, R-ketamine (10
mg/kg, intraperitoneal (i.p.)) or rapastinel (10 mg/kg, i.p.) significantly
attenuated the increased immobility time in the susceptible mice, compared with
the vehicle-treated group. In the sucrose preference test, both compounds
significantly enhanced the reduced preference in susceptible mice 2, 4, or 7 days
after a single injection. All mice were sacrificed 8 days after a single
injection. Western blot analyses showed that R-ketamine, but not rapastinel,
significantly attenuated the reduced brain-derived neurotrophic factor (BDNF)
TrkB signaling, postsynaptic density protein 95 (PSD-95), and GluA1 (a subtype of
alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor) in the
prefrontal cortex, dentate gyrus, and CA3 of the hippocampus in the susceptible
mice. In contrast, both compounds had no effect against the increased BDNF-TrkB
signaling, PSD-95, and GluA1 seen in the nucleus accumbens of susceptible mice.
Moreover, sustained antidepressant effect of R-ketamine (3 mg/kg, intravenous
(i.v.)), but not rapastinel (3 mg/kg, i.v.), was detected 7 days after a single
dose. CONCLUSIONS: These results highlight R-ketamine as a longer lasting
antidepressant compared with rapastinel in social defeat stress model. It is
likely that synaptogenesis including BDNF-TrkB signaling in the prefrontal cortex
(PFC) and hippocampus may be required for the mechanisms promoting this sustained
antidepressant effect.
PMID- 27488195
TI - Assessment of pollutant load emission from combined sewer overflows based on the
online monitoring.
AB - Cities equipped with combined sewer systems discharge during wet weather a lot of
pollutants into receiving waters by combined storm overflows (CSOs). According to
the Polish legislation, CSOs should be activated no more than ten times per year,
but in Lodz, most of the 18 existing CSOs operate much more frequently. To assess
the pollutant load emitted by one of the existing CSOs, the sensors for measuring
the concentration of total suspended solids (SOLITAX sc) and dissolved chemical
oxygen demand (UVAS plus) installed in the overflow chamber as well as two
flowmeters placed in the outflow sewer were used. In order to check the data from
sensors, laboratory tests of combined wastewater quality were conducted
simultaneously. For the analysis of the total pollutant load emitted from the
overflow, the raw data was denoised using the Savitzky-Golay method. Comparing
the load calculated from the analytical results to online smoothed measurements,
negligible differences were found, which confirms the usefulness of applying the
sensors in the combined sewer system. Online monitoring of the quantity and
quality of wastewater emitted by the combined sewer overflows to water receivers,
provides a considerable amount of data very useful for combined sewerage
upgrading based on computer modelling, and allows for a significant reduction of
laboratory analysis.
PMID- 27488196
TI - A system dynamics approach for hospital waste management in a city in a
developing country: the case of Nablus, Palestine.
AB - Hospitals and health centers provide a variety of healthcare services and
normally generate hazardous waste as well as general waste. General waste has a
similar nature to that of municipal solid waste and therefore could be disposed
of in municipal landfills. However, hazardous waste poses risks to public health,
unless it is properly managed. The hospital waste management system encompasses
many factors, i.e., number of beds, number of employees, level of service,
population, birth rate, fertility rate, and not in my back yard (NIMBY) syndrome.
Therefore, this management system requires a comprehensive analysis to determine
the role of each factor and its influence on the whole system. In this research,
a hospital waste management simulation model is presented based on the system
dynamics technique to determine the interaction among these factors in the system
using a software package, ithink. This model is used to estimate waste
segregation as this is important in the hospital waste management system to
minimize risk to public health. Real data has been obtained from a case study of
the city of Nablus, Palestine to validate the model. The model exhibits wastes
generated from three types of hospitals (private, charitable, and government) by
considering the number of both inpatients and outpatients depending on the
population of the city under study. The model also offers the facility to compare
the total waste generated among these different types of hospitals and anticipate
and predict the future generated waste both infectious and non-infectious and the
treatment cost incurred.
PMID- 27488198
TI - Visible Light-Induced Carbonylation Reactions with Organic Dyes as the
Photosensitizers.
AB - Dyes can CO do it: Organic dyes and pigments are usually applied in textile
dyeing, which can be dated back to the Neolithic period. Interestingly, the
possibility to use organic dyes as photoredox catalysts has also been noticed by
organic chemists and applied in organic synthesis. Carbonylation reactions as a
powerful procedure in carbonyl-containing compound preparation have also been
studied. In this manuscript, the recent achievements in using organic dyes as
visible-light sensitizers in carbonylation chemistry are summarized and
discussed.
PMID- 27488197
TI - Determination of total arsenic and arsenic species in drinking water, surface
water, wastewater, and snow from Wielkopolska, Kujawy-Pomerania, and Lower
Silesia provinces, Poland.
AB - Arsenic is a ubiquitous element which may be found in surface water, groundwater,
and drinking water. In higher concentrations, this element is considered
genotoxic and carcinogenic; thus, its level must be strictly controlled. We
investigated the concentration of total arsenic and arsenic species: As(III),
As(V), MMA, DMA, and AsB in drinking water, surface water, wastewater, and snow
collected from the provinces of Wielkopolska, Kujawy-Pomerania, and Lower Silesia
(Poland). The total arsenic was analyzed by inductively coupled plasma mass
spectrometry (ICP-MS), and arsenic species were analyzed with use of high
performance liquid chromatography inductively coupled plasma mass spectrometry
(HPLC/ICP-MS). Obtained results revealed that maximum total arsenic concentration
determined in drinking water samples was equal to 1.01 MUg L(-1). The highest
concentration of total arsenic in surface water, equal to 3778 MUg L(-1) was
determined in Trujaca Stream situated in the area affected by geogenic arsenic
contamination. Total arsenic concentration in wastewater samples was comparable
to those determined in drinking water samples. However, significantly higher
arsenic concentration, equal to 83.1 +/- 5.9 MUg L(-1), was found in a snow
sample collected in Legnica. As(V) was present in all of the investigated
samples, and in most of them, it was the sole species observed. However, in snow
sample collected in Legnica, more than 97 % of the determined concentration,
amounting to 81 +/- 11 MUg L(-1), was in the form of As(III), the most toxic
arsenic species.
PMID- 27488199
TI - Rearfoot Transcutaneous Oximetry is a Useful Tool to Highlight Ischemia of the
Heel.
AB - PURPOSE: To demonstrate the usefulness of rearfoot transcutaneous oximetry to
assess the peripheral arterial disease in diabetic patients with heel ulcer.
METHODS: From our database of 550 critical limb ischemia diabetic patients
followed after a percutaneous transluminal angioplasty, we have selected patients
with below the knee arterial disease. Patients were grouped according to the
dorsal transcutaneous oximetry value (Group A < 30 mmHg; Group B >= 30 mmHg).
Patients of Group B had a second oximetry performed at the rearfoot, close to the
lesion localized in all cases at the heel. Finally, the analysis of the arterial
pattern disease has been done. RESULTS: We selected 191 patients: Group A (151
patients), dorsal transcutaneous oximetry of 11.8 +/- 0.7 mmHg; Group B (40
patients), dorsal transcutaneous oximetry of 44.2 +/- 10.1 mmHg. In Group B,
rearfoot oximetry was 20.5 +/- 5 mmHg, significantly lower than dorsal oximetry
(p = 0.0179). The anterior tibial artery was involved in all patients of Group A.
In Group B, the anterior tibial artery was involved in 15 subjects and never
alone; the posterior tibial artery was involved in 20 subjects and in 11 cases
alone. The peroneal artery was affected in 20 subjects and in 14 patients alone.
CONCLUSION: When a heel lesion is present and the transcutaneous oximetry
recorded on the dorsum of the foot does not confirm the presence of critical limb
ischemia (not <=30 mmHg), a second oximetry recorded on the rearfoot is useful to
point out ischemia of the peroneal artery and/or of the posterior tibial artery.
PMID- 27488200
TI - Phytoplankton responses to temperature increases are constrained by abiotic
conditions and community composition.
AB - Effects of temperature changes on phytoplankton communities seem to be highly
context-specific, but few studies have analyzed whether this context specificity
depends on differences in the abiotic conditions or in species composition
between studies. We present an experiment that allows disentangling the
contribution of abiotic and biotic differences in shaping the response to two
aspects of temperature change: permanent increase of mean temperature versus
pulse disturbance in form of a heat wave. We used natural communities from six
different sites of a floodplain system as well as artificially mixed communities
from laboratory cultures and grew both, artificial and natural communities, in
water from the six different floodplain lakes (sites). All 12 contexts (2
communities * 6 sites) were first exposed to three different temperature levels
(12, 18, 24 degrees C, respectively) and afterward to temperature pulses (4
degrees C increase for 7 h day(-1)). Temperature-dependent changes in biomass and
community composition depended on the initial composition of phytoplankton
communities. Abiotic conditions had a major effect on biomass of phytoplankton
communities exposed to different temperature conditions, however, the effect of
biotic and abiotic conditions together was even more pronounced. Additionally,
phytoplankton community responses to pulse temperature effects depended on the
warming history. By disentangling abiotic and biotic effects, our study shows
that temperature-dependent effects on phytoplankton communities depend on both,
biotic and abiotic constraints.
PMID- 27488201
TI - Combining Passive Sampling with Toxicological Characterization of Complex
Mixtures of Pollutants from the Aquatic Environment.
AB - The combination of polymer-based passive sampling to collect complex
environmental mixtures of pollutants, the transfer of these mixtures into
bioassays, and their related toxicological characterization is still in its
infancy. However, this approach has considerable potential to improve
environmental hazard and risk assessment for two reasons. First, the passive
sampler collects a broad range of chemicals representing the fraction of
compounds available for diffusion and (bio)uptake, excluding a large part of the
matrix; thus, extensive sample cleanup which could discriminate certain compounds
can be avoided. Second, the toxicological characterization of samples using
bioassays is complementary to chemical (target) analysis within environmental
monitoring because it captures all chemicals exerting the same mode of toxic
action and acting jointly in mixtures, thus providing a comprehensive picture of
their overall combined effects. The scientific literature describes a range of
examples from the water phase where passive sampling is usually carried out in
the kinetic uptake regime for most chemicals although some may already have
reached equilibrium. The composition of the chemical mixture changes from the
water phase to the passive sampling material because of kinetic effects and
polymer/water partition coefficients which depend on the chemicals'
hydrophobicity. In contrast, only a few applications in sediment and biota have
been described, but amongst these some pioneering studies have demonstrated the
feasibility and potential of this combined approach. This chapter gives an
overview of what has been carried out in this research area, focusing on
opportunities and challenges, and points out desirable future developments with a
focus on the importance of choosing a suitable combination of sampling and dosing
to transfer (or re-establish) the environmental mixture into the bioassay.
PMID- 27488202
TI - Rapid reduction of antibodies and improvement of disease activity by
immunoadsorption in Chinese patients with severe systemic lupus erythematosus.
AB - This was an exploratory analysis comparing the safety and efficacy of
immunoadsorption (IAS) combination therapy in severe systemic lupus erythematosus
(SLE) receiving corticosteroid pulse and immunosuppressant treatment. Patients
enrolled all had predominant organ involvement including proteinuria,
thrombocytopenia, pericardial effusion, and cerebral involvement requiring
corticosteroid pulse treatment. Fifty-two patients in study group received IAS
plus corticosteroid and cyclophosphamide treatment. Fifty-two patients in non-IAS
group received corticosteroid and cyclophosphamide treatment. Outcome measurement
included C3, dsDNA, AnuA, and SLE disease activity index (SLEDAI) 2k score and in
particular cases, proteinuria quantification and platelet count. Disease activity
dropped significantly in both groups. Improvement of disease activity markers was
more significant in study group than that in non-IAS group. The lower dosage of
steroid in study group suggested the steroid-sparing effect of IAS. No severe
adverse effect occurred during IAS. Our study suggested IAS as an additional
therapy to steroid pulse and immunosuppressant in treating severe SLE.
PMID- 27488203
TI - Endocannabinoids participate in placental apoptosis induced by hypoxia inducible
factor-1.
AB - During pregnancy, apoptosis is a physiological event critical in the remodeling
and aging of the placenta. Increasing evidence has pointed towards the relevance
of endocannabinoids (ECs) and hypoxia as modulators of trophoblast cell death.
However, the relation between these factors is still unknown. In this report, we
evaluated the participation of ECs in placental apoptosis induced by cobalt
chloride (CoCl2), a hypoxia mimicking agent that stabilizes the expression of
hypoxia inducible factor-1 alpha (HIF-1alpha). We found that HIF-1alpha
stabilization decreased FAAH mRNA and protein levels, suggesting an increase in
ECs tone. Additionally, CoCl2 incubation and Met-AEA treatment reduced cell
viability and increased TUNEL-positive staining in syncytiotrophoblast layer.
Immunohistochemical analysis demonstrated Bax and Bcl-2 protein expression in the
cytoplasm of syncytiotrophoblast. Finally, HIF-1alpha stabilization produced an
increase in Bax/Bcl-2 ratio, activation of caspase 3 and PARP cleavage. All these
changes in apoptotic parameters were reversed with AM251, a CB1 antagonist. These
results demonstrate that HIF-1alpha may induce apoptosis in human placenta via
intrinsic pathway by a mechanism that involves activation of CB1 receptor
suggesting a role of the ECs in this process.
PMID- 27488204
TI - Alcohol and Opioid Use Disorder in Older Adults: Neglected and Treatable
Illnesses.
AB - The purpose of this article is to provide an overview of alcohol use disorder
(AUD) and opioid use disorder (OUD) in older adults for general psychiatrists.
The rapid growth of the geriatric population in the USA has wide-ranging
implications as the baby boomer generation ages. Various types of substance use
disorders (SUDs) are common in older adults, and they often take a greater toll
on affected older adults than on younger adults. Due to multiple reasons, SUDs in
older adults are often under-reported, under-detected, and under-treated. Older
adults often use substances, which leads to various clinical problems. Space
limitations prevents a comprehensive review; therefore, we primarily focus on
alcohol use disorder and the problem of opioid use disorder, with more emphasis
given to the latter, because the opioid use epidemic in the USA has gained much
attention. We reviewed the literature on the topics, integrated across geriatric
psychiatry, addiction psychiatry, research, and national trends. We discuss
unique vulnerabilities of older adults to SUDs with regard to management of SUDs
in older adults, medication-assisted treatment (MAT), and psychosocial
treatments. We encourage general psychiatrists to raise their awareness of SUDs
in older adults and to provide brief intervention or referral for further
assessment.
PMID- 27488205
TI - Pet Ownership and the Risk of Dying.
PMID- 27488206
TI - An Algorithm and R Program for Fitting and Simulation of Pharmacokinetic and
Pharmacodynamic Data.
AB - BACKGROUND AND OBJECTIVES: Pharmacokinetic/pharmacodynamic link models are widely
used in dose-finding studies. By applying such models, the results of initial
pharmacokinetic/pharmacodynamic studies can be used to predict the potential
therapeutic dose range. This knowledge can improve the design of later
comparative large-scale clinical trials by reducing the number of participants
and saving time and resources. However, the modeling process can be challenging,
time consuming, and costly, even when using cutting-edge, powerful
pharmacological software. Here, we provide a freely available R program for
expediently analyzing pharmacokinetic/pharmacodynamic data, including data
importation, parameter estimation, simulation, and model diagnostics. METHODS:
First, we explain the theory related to the establishment of the
pharmacokinetic/pharmacodynamic link model. Subsequently, we present the
algorithms used for parameter estimation and potential therapeutic dose
computation. The implementation of the R program is illustrated by a clinical
example. The software package is then validated by comparing the model parameters
and the goodness-of-fit statistics generated by our R package with those
generated by the widely used pharmacological software WinNonlin. RESULTS: The
pharmacokinetic and pharmacodynamic parameters as well as the potential
recommended therapeutic dose can be acquired with the R package. The validation
process shows that the parameters estimated using our package are satisfactory.
CONCLUSIONS: The R program developed and presented here provides pharmacokinetic
researchers with a simple and easy-to-access tool for
pharmacokinetic/pharmacodynamic analysis on personal computers.
PMID- 27488207
TI - The first Turkish illustrated surgical textbook 'Cerrahiyetu'l-Haniyye'.
PMID- 27488208
TI - The Selection and Control of Starting Materials Should be Governed by Science and
Risk-Based Approaches.
PMID- 27488209
TI - Getting Burned by Lactic Acid.
PMID- 27488210
TI - Circulating PCSK9 levels and CETP plasma activity are independently associated in
patients with metabolic diseases.
AB - BACKGROUND: PCSK9 inhibition is a new powerful cholesterol-lowering strategy.
Recently, it was reported that CETP inhibitors influence PCSK9 levels as an off
target effect. We explored the relationship between circulating PCSK9 levels and
CETP activity in patients with metabolic disease who were not on lipid-lowering
therapy. METHODS: Plasma CETP activity and PCSK9 levels were measured in 450
participants (median age, 58 years; 49 % women) who attended the metabolism unit
because of metabolic syndrome (MetS) (78 %), atherogenic dyslipidemia (32 %),
obesity (50 %), type 2 diabetes mellitus (72 %), and other risk factors (13 %). A
6 week lipid-lowering drug wash-out period was established in treated patients.
RESULTS: Both PCSK9 levels and CETP activity were higher in patients with an
increasing number of MetS components. PCSK9 levels were positively correlated
with CETP activity in the entire cohort (r = 0.256, P < 0.0001) independent of
age, gender, body mass index (BMI), systolic blood pressure (SBP), LDL
cholesterol (LDL-C), triglycerides and glucose. Individuals with the loss-of
function PCSK9 genetic variant rs11591147 (R46L) had lower levels of PCSK9 (36.5
%, P < 0.0001) and LDL-C (17.8 %, P = 0.010) as well as lower CETP activity
(10.31 %, P = 0.009). This association remained significant in the multiple
regression analysis even after adjusting for gender, age, BMI, LDL-C,
triglycerides, glucose, lecithin-cholesterol acyltransferase, SBP and MetS (P =
0.003). CONCLUSIONS: Our data suggest a metabolic association between PCSK9 and
CETP independent of lipid-lowering treatment. The clinical implications of this
metabolic relationship could be relevant for explaining the effect of PCSK9 and
CETP inhibition on overall lipid profiles.
PMID- 27488213
TI - Use of PlasmaJet for Peritoneal Carcinomatosis in Ovarian Cancer.
AB - OBJECTIVE: This study aimed to assess the role and complications of extensive
cytoreduction with PlasmaJet (Plasma Surgical, Roswell, Ga) in ovarian cancer
with peritoneal carcinomatosis. MATERIALS: All patients undergoing primary,
secondary, or interval debulking surgery for ovarian cancer and treated with
PlasmaJet between October 2013 and February 2015 were analyzed. RESULTS: Nineteen
patients were enrolled. The median operative time was 270 minutes, median blood
loss was 700 mL, and median length of stay was 9 days. In all patients, complete
resection of all macroscopic disease was achieved.We used PlasmaJet to remove
peritoneal carcinomatosis on the abdominal peritoneum, intestinal mesentery,
bowel serosa, and diaphragmatic region. Overall, we treated 66 organs with
PlasmaJet in our series. No bowel or urological fistulas were observed. According
to the Clavien-Dindo classification, 13 adverse events were recorded at grade 2
or lesser. We observed only 1 grade 3 adverse event. No postoperative mortality
was recorded. CONCLUSIONS: In our series, the PlasmaJet seems to be an efficient
device for tumor ablation or dissection to obtain complete resection of all
macroscopic disease in patients with peritoneal carcinomatosis.
PMID- 27488212
TI - Randomized Trial of Computerized Cognitive Behavioral Therapy for Alcohol Use
Disorders: Efficacy as a Virtual Stand-Alone and Treatment Add-On Compared with
Standard Outpatient Treatment.
AB - BACKGROUND: Cognitive behavioral therapy (CBT) is an evidence-based treatment for
alcohol use disorders (AUDs), yet is rarely implemented with high fidelity in
clinical practice. Computer-based delivery of CBT offers the potential to address
dissemination challenges, but to date there have been no evaluations of a web
based CBT program for alcohol use within a clinical sample. METHODS: This study
randomized treatment-seeking individuals with a current AUD to 1 of 3 treatments
at a community outpatient facility: (i) standard treatment as usual (TAU); (ii)
TAU plus on-site access to a computerized CBT targeting alcohol use (TAU +
CBT4CBT); or (iii) CBT4CBT plus brief weekly clinical monitoring (CBT4CBT +
monitoring). Participant alcohol use was assessed weekly during an 8-week
treatment period, as well as 1, 3, and 6 months after treatment. RESULTS: Sixty
eight individuals (65% male; 54% African American) were randomized (TAU = 22; TAU
+ CBT4CBT = 22; CBT4CBT + monitoring = 24). There were significantly higher rates
of treatment completion among participants assigned to 1 of the CBT4CBT
conditions compared to TAU (Wald = 6.86, p < 0.01). Significant reductions in
alcohol use were found across all conditions within treatment, with participants
assigned to TAU + CBT4CBT demonstrating greater increases in percentage of days
abstinent (PDA) compared to TAU, t(536.4) = 2.68, p < 0.01, d = 0.71, 95% CI
(0.60, 3.91), for the full sample. Preliminary findings suggest the estimated
costs of all self-reported AUD-related services utilized by participants were
considerably lower for those assigned to CBT4CBT conditions compared to TAU, both
within treatment and during follow-up. CONCLUSIONS: This trial demonstrated the
safety, feasibility, and preliminary efficacy of web-based CBT4CBT targeting
alcohol use. CBT4CBT was superior to TAU at increasing PDA when delivered as an
add-on, and it was not significantly different from TAU or TAU + CBT4CBT when
delivered with clinical monitoring only.
PMID- 27488214
TI - Current South African clinical Practice in Debulking Surgery for Ovarian Cancer.
AB - INTRODUCTION: The aim of this study was to assess practice patterns and rationale
with regard to debulking surgery for advanced epithelial ovarian carcinoma among
South African Gynaecological oncologists. METHODS: A survey was distributed to
all practicing gynecological oncologists in South Africa. It was structured to
assess definitions of optimal debulking, procedures used to achieve optimal
debulking, and reasons for not performing specific procedures. Respondents were
also asked to report on experience and additional surgical training to improve
skill in performing ultra-radical debulking surgery. RESULTS: Eighty percent of
gynecological oncologists completed the survey. Sixty percent of respondents
reported that they view optimal debulking as no visible disease, and this was
achieved in 63% of surgical cases. The most common barriers to optimal debulking
were medical comorbidities (85%), followed by lack of expertise in ultra-radical
debulking surgery (55%) and advanced patient age (40%). At operation, the most
common disease findings precluding optimal debulking were large volume confluent
peritoneal disease and confluent diaphragmatic disease. All of the surgeons
perform excision of bulky pelvic and lower paraaortic nodes themselves. Bowel
resections are often performed with the help of a colleague, but more than half
of the respondents never perform diaphragmatic stripping, resection of liver
metastases, distal pancreatic resection, or ablation of peritoneal metastases.
Overall, most participants seem to regularly perform debulking procedures in the
pelvis but are less comfortable with resection of upper abdominal or peritoneal
disease. Most common reasons for not performing procedures were concerns about
patient morbidity and concerns regarding benefit. Fifty percent of respondents
also reported a lack of personal expertise in performing ultra-radical debulking
procedures. CONCLUSIONS: The progression of South African Gynaecological
Oncologist towards more aggressive debulking surgery is following international
trends, but many of the surgeons report a lack of experience in ultra-radical
debulking surgery, especially in the upper abdomen.
PMID- 27488215
TI - Primary Placement of Incisional Negative Pressure Wound Therapy at Time of
Laparotomy for Gynecologic Malignancies.
AB - OBJECTIVE: Wound complications are an important cause of postoperative morbidity
amongst patient with gynecologic malignancies. We evaluated whether the placement
of prophylactic negative pressure wound therapy (NPWT) at the time of laparotomy
for gynecologic cancer surgery reduces wound complication rates. METHODS: A
retrospective analysis of patients undergoing laparotomy with primary wound
closure performed by a gynecologic oncologist at a single academic institution
over a 5-year study period was performed. Patients who had placement of
prophylactic NPWT dressing were compared with patients with a standard closure.
Postoperative outcomes were examined. RESULTS: A total of 230 patients were
identified: 208 women received standard wound care, 22 received NPWT. Groups were
similar in age, prevalence of diabetes, tobacco use, and number of previous
abdominal procedures. Intraoperative factors including length of procedure and
transfusion requirements were similar. Body mass index for patients receiving
standard treatment was 30.67 compared with 41.29 for NPWT group (P < 0.001).
Incidence of all wound complications was 19.7% for those receiving standard
treatment versus 27.3% for NPWT group (P = 0.40). Length of hospital stay was
similar between the 2 groups (5.25 vs 6.22 days, P = 0.20). There were 3 hospital
readmissions for wound complications-none occurred in women with a prophylactic
NPWT dressing. CONCLUSIONS: Despite significantly higher obesity rates, patients
with prophylactic NPWT dressing placement had similar rates of wound
complications. Our findings suggest a potential therapeutic benefit in the use of
prophylactic NPWT for the reduction of wound complications in this high-risk
gynecologic oncology patient population.
PMID- 27488216
TI - Incidence and Characteristics of Unsuspected Neoplasia Discovered in High-Risk
Women Undergoing Risk Reductive Bilateral Salpingooophorectomy.
AB - OBJECTIVE: Risk reducing salpingooophorectomy is recommended to women with a
BReast CAncer susceptibility gene (BRCA) 1 or 2 germline mutation to reduce the
risk of ovarian cancer. The incidence of unsuspected neoplasia varies in the
literature. The purpose of this study was to identify the rate of unsuspected
neoplasia in a high-risk Australian population, discuss their management, and
assess the clinical outcome. METHOD: This is a retrospective review of all women
undergoing risk reductive salpingooophorectomy between January 2006 and December
2014. The medical, operative, and pathology results were reviewed. The specimens
were assessed using the Sectioning and Extensively Examining the Fimbriated End
protocol to the fallopian tube, and the ovary was also examined using 2 to 3 mm
sectioning. RESULTS: During the study period, 138 patients underwent risk
reducing salpingooophorectomy for a known BRCA 1 or 2 germline mutation or a high
risk personal or family history of ovarian cancer. Five patients with neoplasia
were identified, 2 with invasive tubal carcinoma and 3 with serous tubal
intraepithelial carcinoma (STIC), giving an overall incidence of 3.62%. Invasive
tubal carcinoma occurred in 1 woman with a BRCA 1 mutation and 1 woman with a
BRCA 2 mutation. The incidence of carcinoma in women with either a BRCA 1 or 2
germline mutation was subsequently 2.78%. STIC occurred in 2 women with a BRCA 1
germline mutation and 1 woman carrying a BRCA 2 germline mutation. The incidence
of STIC in women with either a BRCA 1 or 2 germline mutation was subsequently
4.17%. Of the patients with STIC, all 3 remain disease free at an average follow
up period of 79.33 months. CONCLUSIONS: In this retrospective review, we found
the incidence of neoplasia within a high-risk Australian population undergoing
risk-reducing bilateral salpingo-oophorectomy to be 3.62%. The incidence of STIC
was 2.17%. During our follow-up period, all patients with STIC remained disease
free.
PMID- 27488217
TI - Physical Activity Correlates, Barriers, and Preferences for Women With
Gynecological Cancer.
AB - OBJECTIVE: Physical activity is associated with improved health outcomes for
people with cancer. We aimed to identify physical activity correlates, barriers,
and preferences among women with gynecological cancer. METHODS AND MATERIALS: A
self-administered questionnaire was completed by 101 women diagnosed with
gynecological cancer (mostly ovarian cancer [59%] and endometrial cancer [23%])
within the previous 2 years, at 2 major hospitals in Sydney, Australia. Physical
activity was measured for the past 7 days. Thirteen potential barriers were
scored on a 5-point scale. Associations with physical activity were assessed
using Spearman correlations (rs) and multivariate logistic regression. RESULTS:
Factors associated with being sufficiently active (>=150 min/wk physical
activity) were being in the follow-up phase of the cancer trajectory (odds ratio
[OR], 7.0; 95% confidence interval [CI], 1.5 to 33.4 compared with other phases)
and prediagnosis physical activity (OR, 4.6; 95% CI, 1.1 to 18.5 for the highest
vs lowest tertile). The most common barriers were "too tired" and "not well
enough," and both were associated with lower physical activity (rs, -0.20 and
0.22, respectively). The odds of having disease-specific barriers was higher for
women with ovarian cancer (OR, 4.6; P = 0.04) and women receiving chemotherapy or
radiation therapy (OR, 8.3; P = 0.008). "Lack of interest" (rs, -0.26) and "never
been active" (rs, -0.23) were also inversely correlated with physical activity,
although less common. Forty-three percent of women indicated that they were
extremely or very interested to have a one-to-one session with an exercise
physiologist. Participants' preferred time of starting a physical activity
program was 3 to 6 months after treatment (26%) or during treatment (23%).
Walking was the preferred type of physical activity. CONCLUSIONS: Strategies to
increase physical activity among women with gynecological cancer should include a
focus on reducing disease-specific barriers and target women who have done little
physical activity in the past or who are in the treatment phases of care.
PMID- 27488211
TI - Erythropoietin and mTOR: A "One-Two Punch" for Aging-Related Disorders
Accompanied by Enhanced Life Expectancy.
AB - Life expectancy continues to increase throughout the world, but is accompanied by
a rise in the incidence of non-communicable diseases. As a result, the benefits
of an increased lifespan can be limited by aging-related disorders that
necessitate new directives for the development of effective and safe treatment
modalities. With this objective, the mechanistic target of rapamycin (mTOR), a
289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1
(mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40),
AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type
information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have
generated significant excitement for furthering novel therapies applicable to
multiple systems of the body. Yet, the biological and clinical outcome of these
pathways can be complex especially with oversight of cell death mechanisms that
involve apoptosis and autophagy. Growth factors, and in particular erythropoietin
(EPO), are one avenue under consideration to implement control over cell death
pathways since EPO can offer potential treatment for multiple disease entities
and is intimately dependent upon mTOR signaling. In experimental and clinical
studies, EPO appears to have significant efficacy in treating several disorders
including those involving the developing brain. However, in mature populations
that are affected by aging-related disorders, the direction for the use of EPO to
treat clinical disease is less clear that may be dependent upon a number of
factors including the understanding of mTOR signaling. Continued focus upon the
regulatory elements that control EPO and mTOR signaling could generate critical
insights for targeting a broad range of clinical maladies.
PMID- 27488218
TI - Predictive Capacity of 3 Comorbidity Indices in Estimating Survival Endpoints in
Women With Early-Stage Endometrial Carcinoma.
AB - OBJECTIVE: The negative impact of comorbidity on survival in women with
endometrial carcinoma (EC) is well-known. Few validated comorbidity indices are
available for clinical use, such as the Charlson Comorbidity Index (CCI), the Age
Adjusted CCI (AACCI), and the Adult Comorbidity Evaluation-27 (ACE-27). The aim
of the study is to determine which index best correlates with survival endpoints
in women with EC. MATERIALS AND METHODS: We identified 1132 women with early
stage EC treated at an academic center. Three scores were calculated for each
patient using CCI, AACCI, and ACE-27 at the time of hysterectomy. Univariate and
multivariable modeling was used to determine predictors of survival. RESULTS: For
each of the studied comorbidity indices, the highest scores were significantly
correlated with poorer overall survival. The hazard ratio of death from any cause
was 3.92 for AACCI, 2.25 for CCI, and 1.57 for ACE-27. All 3 indices were
independent predictors of overall survival with a P value of less than 0.001 on
multivariate analysis. In addition, lymphovascular space invasion, lower uterine
segment involvement, and tumor grade were predictors of overall survival.
Lymphovascular space invasion, grade (P < 0.001), and high AACCI score were the
only significant predictors of recurrence-free survival (RFS). Lymphovascular
space invasion and tumor grade were the only 2 predictors of disease-specific
survival. CONCLUSIONS: Although all 3 studied comorbidity indices were
significant predictors of overall survival in women with early-stage EC, AACCI
showed a stronger association. It should be considered for evaluating comorbidity
in women with early-stage EC.
PMID- 27488219
TI - Altered Mental Status in ICU Patients: Diagnostic Yield of Noncontrast Head CT
for Abnormal and Communicable Findings.
AB - OBJECTIVE: To evaluate the diagnostic yield of noncontrast head CT for acute
communicable findings in ICU patients specifically scanned for altered mental
status. DESIGN: Retrospective observational cohort study. SETTING: University
Hospital Neuroscience, Medical, and Surgical ICUs. PATIENTS: ICU patients with
new-onset altered mental status. INTERVENTION: Noncontrast head CT. MEASUREMENTS
AND MAIN RESULTS: Reports on head CTs from two university hospitals performed for
the sole indication of altered mental status in ICU patients between July 2011
and June 2013 were reviewed for 1) acute (new or worsening) hemorrhage, 2) mass
effect/herniation, 3) infarction, and 4) hydrocephalus. Subgroup analyses of
positive findings were performed by 1) ICU group type, 2) age, and 3) race. A
total of 2,486 head CTs were performed in 1,357 patients whose age ranged from 14
to 116 years (median, 59; mean, 57.6 +/- 16). Acute communicable findings in at
least one of four categories were present in 22.8% (566/2,486) of examinations,
with hydrocephalus being most common (11.5% [286/2,486]). The frequency of any
acute communicable findings in neuroscience, medical, and surgical ICUs was 28.6%
(471/1,648), 9.8% (43/440), and 13.1% (52/398), respectively. Neuroscience ICU
head CTs had significantly higher rates of acute communicable findings in all
categories, except for acute infarction, compared with the other two ICUs (p <
0.001). Acute hydrocephalus (13.6% vs 7.4%; p < 0.001) and mass effect (6.7% vs
4.3%; p = 0.01) were more common in patients less than 65 years. For other acute
categories, no significant difference was noted by age. There was no significant
difference in the likelihood of a positive examination by race. CONCLUSIONS:
Almost one in four head CTs in a university ICU patient population performed for
primary indication of altered mental status yields abnormal communicable
findings. In this patient population, utilization management barriers to
examination ordering should be minimized.
PMID- 27488220
TI - Functional Status Score for the ICU: An International Clinimetric Analysis of
Validity, Responsiveness, and Minimal Important Difference.
AB - OBJECTIVES: To evaluate the internal consistency, validity, responsiveness, and
minimal important difference of the Functional Status Score for the ICU, a
physical function measure designed for the ICU. DESIGN: Clinimetric analysis.
SETTINGS: Five international datasets from the United States, Australia, and
Brazil. PATIENTS: Eight hundred nineteen ICU patients. INTERVENTION: None.
MEASUREMENTS AND MAIN RESULTS: Clinimetric analyses were initially conducted
separately for each data source and time point to examine generalizability of
findings, with pooled analyses performed thereafter to increase power of
analyses. The Functional Status Score for the ICU demonstrated good to excellent
internal consistency. There was good convergent and discriminant validity, with
significant and positive correlations (r = 0.30-0.95) between Functional Status
Score for the ICU and other physical function measures, and generally weaker
correlations with nonphysical measures (|r| = 0.01-0.70). Known group validity
was demonstrated by significantly higher Functional Status Score for the ICU
scores among patients without ICU-acquired weakness (Medical Research Council sum
score, >= 48 vs < 48) and with hospital discharge to home (vs healthcare
facility). Functional Status Score for the ICU at ICU discharge predicted post
ICU hospital length of stay and discharge location. Responsiveness was supported
via increased Functional Status Score for the ICU scores with improvements in
muscle strength. Distribution-based methods indicated a minimal important
difference of 2.0-5.0. CONCLUSIONS: The Functional Status Score for the ICU has
good internal consistency and is a valid and responsive measure of physical
function for ICU patients. The estimated minimal important difference can be used
in sample size calculations and in interpreting studies comparing the physical
function of groups of ICU patients.
PMID- 27488221
TI - Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake,
Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation.
AB - AIM: We investigated the uptake and pharmacokinetics of l-ergothioneine (ET), a
dietary thione with free radical scavenging and cytoprotective capabilities,
after oral administration to humans, and its effect on biomarkers of oxidative
damage and inflammation. RESULTS: After oral administration, ET is avidly
absorbed and retained by the body with significant elevations in plasma and whole
blood concentrations, and relatively low urinary excretion (<4% of administered
ET). ET levels in whole blood were highly correlated to levels of hercynine and S
methyl-ergothioneine, suggesting that they may be metabolites. After ET
administration, some decreasing trends were seen in biomarkers of oxidative
damage and inflammation, including allantoin (urate oxidation), 8-hydroxy-2'
deoxyguanosine (DNA damage), 8-iso-PGF2alpha (lipid peroxidation), protein
carbonylation, and C-reactive protein. However, most of the changes were non
significant. INNOVATION: This is the first study investigating the administration
of pure ET to healthy human volunteers and monitoring its uptake and
pharmacokinetics. This compound is rapidly gaining attention due to its unique
properties, and this study lays the foundation for future human studies.
CONCLUSION: The uptake and retention of ET by the body suggests an important
physiological function. The decreasing trend of oxidative damage biomarkers is
consistent with animal studies suggesting that ET may function as a major
antioxidant but perhaps only under conditions of oxidative stress. Antioxid.
Redox Signal. 26, 193-206.
PMID- 27488222
TI - Exposure to bacterial endotoxin generates a distinct strain of alpha-synuclein
fibril.
AB - A single amyloidogenic protein is implicated in multiple neurological diseases
and capable of generating a number of aggregate "strains" with distinct
structures. Among the amyloidogenic proteins, alpha-synuclein generates multiple
patterns of proteinopathies in a group of diseases, such as Parkinson disease
(PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).
However, the link between specific conformations and distinct pathologies, the
key concept of the strain hypothesis, remains elusive. Here we show that in the
presence of bacterial endotoxin, lipopolysaccharide (LPS), alpha-synuclein
generated a self-renewable, structurally distinct fibril strain that consistently
induced specific patterns of synucleinopathies in mice. These results suggest
that amyloid fibrils with self-renewable structures cause distinct types of
proteinopathies despite the identical primary structure and that exposure to
exogenous pathogens may contribute to the diversity of synucleinopathies.
PMID- 27488223
TI - Recruitment methods in a clinical trial of provoked vulvodynia: Predictors of
enrollment.
AB - BACKGROUND: Successful recruitment in clinical trials for chronic pain conditions
is challenging, especially in women with provoked vulvodynia due to reluctance in
discussing pain associated with sexual intercourse. The most successful
recruitment methods and the characteristics of women reached with these methods
are unknown. OBJECTIVE: To compare the effectiveness and efficiency of four
recruitment methods and to determine socioeconomic predictors for successful
enrollment in a National Institutes of Health-sponsored multicenter clinical
trial evaluating a gabapentin intervention in women with provoked vulvodynia.
METHODS: Recruitment methods utilized mass mailing, media, clinician referrals
and community outreach. Effectiveness (number of participants enrolled) and
efficiency (proportion screened who enrolled) were determined. Socioeconomic
variables including race, educational level, annual household income,
relationship status, age, menopausal status and employment status were also
evaluated regarding which recruitment strategies were best at targeting specific
cohorts. RESULTS: Of 868 potential study participants, 219 were enrolled. The
most effective recruitment method in enrolling participants was mass mailing ( p
< 0.001). There were no statistically significant differences in efficiency
between recruitment methods ( p = 0.11). Relative to clinician referral, black
women were 13 times as likely to be enrolled through mass mailing (adjusted odds
ratio 12.5, 95% confidence interval, 3.6-43.1) as white women. There were no
differences in enrollment according to educational level, annual income,
relationship status, age, menopausal status, or employment status and recruitment
method. CONCLUSION: In this clinical trial, mass mailing was the most effective
recruitment method. Race of participants enrolled in a provoked vulvodynia trial
was related to the recruitment method.
PMID- 27488224
TI - Assessment of the effectiveness of three different cephalosporin/clavulanate
combinations for the phenotypic confirmation of extended-spectrum beta-lactamase
producing bacteria isolated from urine samples at National Public Health
Laboratory, Kathmandu, Nepal
AB - BACKGROUND: The extended-spectrum beta-lactamase (ESBL) producing bacteria are
present as the serious public health problems due to their resistance to large
number of antibiotics. The main aims of this study were to determine the
prevalence and antibiotic resistance patterns of bacteria producing extended
spectrum beta-lactamases (ESBLs) and to find the suitable
cephalosporin/clavulanate combination for phenotypic confirmation of ESBL
production. METHODS: During the study period from April 2013 to November 2013, a
total of 1003 urine samples from the patients visiting National Public Health
Laboratory, Kathmandu, Nepal were collected and processed. The isolates were
identified with the help of colony characteristics, gram stain and conventional
biochemical tests. Antimicrobial susceptibility testing was performed by Kirby
Bauer disc diffusion method. ESBL production screening was done by using
ceftriaxone, while ESBL production confirmation was done by using three different
3rd generation cephalosporin/clavulanate combinations. RESULTS: Of the 138
isolates, Escherichia coli was the most predominant with 88 (63.8 %) isolates.
Among the antibiotics tested for gram negative bacteria, highest susceptibility
was seen toward imipenem followed by amikacin. Of the total isolates, 68 (49.3 %)
were suspected as ESBL producers. Of these, 44 (64.7 %) were phenotypically
confirmed to be ESBL producers. The majority of ESBL producers were E. coli with
34 (72.3 %) isolates. Of the three different 3rd generation
cephalosporin/clavulanate combinations used, ceftazidime/clavulanate combination
was found to be most effective for phenotypic confirmation of ESBL producers and
was statistically highly significant (P < 0.01). CONCLUSION: Based on the
findings of our study, we recommend to use ceftazidime/clavulanate combination
for phenotypic confirmation of ESBL producers. Routine ESBL testing for
uropathogens along with conventional antibiogram would be useful for proper early
management of all the cases of urinary tract infections.
PMID- 27488225
TI - Shifting blame: Buprenorphine prescribers, addiction treatment, and prescription
monitoring in middle-class America.
AB - Growing nonmedical prescription opioid analgesic use among suburban and rural
Whites has changed the public's perception of the nature of opioid addiction, and
of appropriate interventions. Opioid addiction has been recast as a biological
disorder in which patients are victims of their neurotransmitters and opioid
prescribers are irresponsible purveyors of dangerous substances requiring
controls. This framing has led to a different set of policy responses than the
"War on Drugs" that has focused on heroin trade in poor urban communities; in
response to prescription opioid addiction, prescription drug monitoring programs
and tamper-resistant opioid formulations have arisen as primary interventions in
place of law enforcement. Through the analysis of preliminary findings from
interviews with physicians who are certified to manage opioid addiction with the
opioid pharmaceutical buprenorphine, we argue that an increase in prescriber
monitoring has shifted the focus from addicted people to prescribers as a threat,
paradoxically driving users to illicit markets and constricting their access to
pharmaceutical treatment for opioid addiction. Prescriber monitoring is also
altering clinical cultures of care, as general physicians respond to heightened
surveillance and the psychosocial complexities of treating addiction with either
rejection of opioid dependent patients, or with resourceful attempts to create
support systems for their treatment where none exists.
PMID- 27488228
TI - Boron isotope fractionation in magma via crustal carbonate dissolution.
AB - Carbon dioxide released by arc volcanoes is widely considered to originate from
the mantle and from subducted sediments. Fluids released from upper arc
carbonates, however, have recently been proposed to help modulate arc CO2 fluxes.
Here we use boron as a tracer, which substitutes for carbon in limestone, to
further investigate crustal carbonate degassing in volcanic arcs. We performed
laboratory experiments replicating limestone assimilation into magma at crustal
pressure-temperature conditions and analysed boron isotope ratios in the
resulting experimental glasses. Limestone dissolution and assimilation generates
CaO-enriched glass near the reaction site and a CO2-dominated vapour phase. The
CaO-rich glasses have extremely low delta(11)B values down to -41.50/00,
reflecting preferential partitioning of (10)B into the assimilating melt. Loss of
(11)B from the reaction site occurs via the CO2 vapour phase generated during
carbonate dissolution, which transports (11)B away from the reaction site as a
boron-rich fluid phase. Our results demonstrate the efficacy of boron isotope
fractionation during crustal carbonate assimilation and suggest that low
delta(11)B melt values in arc magmas could flag shallow-level additions to the
subduction cycle.
PMID- 27488226
TI - Brachial artery flow-mediated dilatation and carotid intima-media thickness in
young ED patients with insulin resistance.
AB - The evidence of a close relationship between cardiovascular disease and erectile
dysfunction (ED) is well documented. The aim of this study is to investigate
whether there is an early asymptomatic impairment of the peripheral vasculature
in young ED patients without obvious cardiovascular disease. We studied a total
of 261 ED patients (19-40 years old) and 40 age-matched healthy controls. All
participants received questionnaires of cardiovascular risk factors and erectile
function assessment, were subjected to lab tests of fasting blood sample, and
underwent the ultrasonographic examination of brachial artery flow-mediated
dilation (FMD) and carotid intima-media thickness (c-IMT). Insulin resistance
(IR) was measured by the homeostasis model assessment of insulin resistance (HOMA
IR). Compared with normal human controls, FMD was significantly lower, whereas
the average c-IMT was significantly greater in ED patients. An inverse
correlation was found between FMD and mean c-IMT. The ED patients had
significantly higher levels of fasting glucose, fasting insulin and HOMA-IR
index, but showed relatively lower total testosterone and prolactin levels than
the controls. Both FMD and c-IMT showed a significant correlation with
International Index of Erectile Function-5 questionnaire (IIEF-5) score, age and
HOMA-IR. Multivariate stepwise regression analysis demonstrated that age, HOMA-IR
and IIEF-5 score were the risk factors associated with FMD and c-IMT. In
conclusion, young ED patients in association with IR display diminished FMD and
increased c-IMT. Furthermore, ED, HOMA-IR and age are independent predictors of
the two subclinical atherosclerotic markers.
PMID- 27488227
TI - Emotion dynamics and tinnitus: Daily life data from the "TrackYourTinnitus"
application.
AB - It is well established that emotions influence tinnitus, but the role of emotion
dynamics remains unclear. The present study investigated emotion dynamics in N =
306 users of the "TrackYourTinnitus" application who completed the Mini-Tinnitus
Questionnaire (Mini-TQ) at one assessment point and provided complete data on at
least five assessment points for the following state variables: tinnitus
loudness, tinnitus distress, arousal, valence. The repeated arousal and valence
ratings were used for two operationalizations of emotion dynamics: intra
individual variability of affect intensity (pulse) as well as intra-individual
variability of affect quality (spin). Pearson correlation coefficients showed
that the Mini-TQ was positively correlated with pulse (r = 0.19; p < 0.05) as
well as with spin (r = 0.12; p < 0.05). Multilevel models revealed the following
results: increases in tinnitus loudness were more strongly associated with
increases in tinnitus distress at higher levels of pulse as well as at higher
levels of spin (both p < 0.05), whereby increases in tinnitus loudness correlated
even stronger with increases in tinnitus distress when both pulse as well as spin
were high (p < 0.05). Moreover, increases in spin were associated with a less
favorable time course of tinnitus loudness (p < 0.05). To conclude, equilibrating
emotion dynamics might be a potential target in the prevention and treatment of
tinnitus.
PMID- 27488229
TI - First report of the isolation of Lactococcus garvieae from a platelet concentrate
in Japan.
AB - BACKGROUND: Bacterial contamination of platelet concentrates (PCs) remains a
serious problem in transfusion. We have been conducting sterility tests on all
PCs rejected by blood centers or hospitals due to abnormal appearances. We
recently experienced a case in which discrepant results were obtained between the
methods used to identify a bacterial species isolated from a PC, requiring
further analyses. STUDY DESIGN AND METHODS: Bacteria were isolated from a PC
using the BacT/ALERT system and plate culture. The species was identified using
biochemical tests and molecular analysis. Phylogenetic trees were constructed
using sequences of the 16S ribosomal RNA (rRNA) and superoxide dismutase (sodA)
genes from the bacterial isolate and related species. In addition, the isolate
was cultured at temperatures of 10 degrees C and below to determine its growth
activity at low temperatures. RESULTS: Biochemical tests determined that the
isolate was Streptococcus alactolyticus, whereas molecular analysis determined
that it was Lactococcus garvieae. These two species belonged to different
clusters on the phylogenetic tree. Similar to L. garvieae, the isolate could grow
at 10 degrees C. CONCLUSIONS: We conclude that the isolate was L. garvieae
according to molecular identification and its growth characteristic at 10 degrees
C. Molecular analysis enabled the identification of this species, which was
difficult to classify by biochemical tests. Blood facilities need to be prepared
with multiple techniques, including genetic analysis techniques, for identifying
contaminating bacterial species. L. garvieae can grow at 10 degrees C and can
contaminate both red blood cell concentrates and PCs; thus, this species should
be listed as a cryophilic bacterium that could threaten blood safety.
PMID- 27488230
TI - Sulla carnosa modulates root invertase activity in response to the inhibition of
long-distance sucrose transport under magnesium deficiency.
AB - Being the principal product of photosynthesis, sucrose is involved in many
metabolic processes in plants. As magnesium (Mg) is phloem mobile, an inverse
relationship between Mg shortage and sugar accumulation in leaves is often
observed. Mg deficiency effects on carbohydrate contents and invertase activities
were determined in Sulla carnosa Desf. Plants were grown hydroponically at
different Mg concentrations (0.00, 0.01, 0.05 and 1.50 mM Mg) for one month.
Mineral analysis showed that Mg contents were drastically diminished in shoots
and roots mainly at 0.01 and 0.00 mM Mg. This decline was adversely associated
with a significant increase of sucrose, fructose and mainly glucose in shoots of
plants exposed to severe deficiency. By contrast, sugar contents were severely
reduced in roots of these plants indicating an alteration of carbohydrate
partitioning between shoots and roots of Mg-deficient plants. Cell wall invertase
activity was highly enhanced in roots of Mg-deficient plants, while the vacuolar
invertase activity was reduced at 0.00 mM Mg. This decrease of vacuolar invertase
activity may indicate the sensibility of roots to Mg starvation resulting from
sucrose transport inhibition. 14 CO2 labeling experiments were in accordance with
these findings showing an inhibition of sucrose transport from source leaves to
sink tissues (roots) under Mg depletion. The obtained results confirm previous
findings about Mg involvement in photosynthate loading into phloem and add new
insights into mechanisms evolved by S. carnosa to cope with Mg shortage in
particular the increase of the activity of cell wall invertase.
PMID- 27488231
TI - The safety and efficacy of nivolumab in advanced (metastatic) non-small cell lung
cancer.
AB - INTRODUCTION: Advanced non-small cell lung cancer (NSCLC) is a challenging
oncological problem. Following standard initial therapy, disease progression will
typically develop. Patients with relapsed or refractory disease are left with
limited treatment options. The advent of nivolumab, a monoclonal antibody against
Program Death-1 (PD-1), has substantially changed the outlook for such patients.
AREA COVERED: Nivolumab is the first checkpoint immunotherapeutic agent to gain
regulatory approval for NSCLC. By enabling host immune-mediated cytotoxic
activity against tumor cells, nivolumab induces a partial or complete tumor
response in 15-20% of patients, regardless of number of previous lines of anti
cancer therapy. Nivolumab-related adverse effects are generally milder and less
frequent than those observed with conventional cytotoxic chemotherapy. Although
immune-related adverse events such as fatal pneumonitis have been reported with
nivolumab therapy, most adverse events are reversible with a prompt
immunosuppression. Studies investigating nivolumab in combination with other
agents are ongoing. Expert commentary: Nivolumab represents a significant
breakthrough in the treatment of advanced NSCLC. Its therapeutic role for NSCLC
may soon expand to include consolidation or maintenance setting. Furthermore,
several clinical trials investigating the combination of nivolumab with other
immunologic or non-immunologic treatments are ongoing and these will likely
result in additional roles of nivolumab in NSCLC.
PMID- 27488232
TI - Managing reversal of direct oral anticoagulants in emergency situations.
Anticoagulation Education Task Force White Paper.
AB - Anticoagulation is the cornerstone of prevention and treatment of venous
thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation
(AF). However, the mechanisms by which anticoagulants confer therapeutic benefit
also increase the risk of bleeding. As such, reversal strategies are critical.
Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban,
apixaban, and edoxaban lacked a specific reversal agent. This report is based on
findings from the Anticoagulation Education Task Force, which brought together
patient groups and professionals representing different medical specialties with
an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation,
and reversal agents, to discuss the current status of anticoagulation reversal
and fundamental changes in management of bleeding associated with DOACs
occasioned by the approval of idarucizumab, a specific reversal agent for
dabigatran, as well as recent clinical data on specific reversal agents for
factor Xa inhibitors. Recommendations are given for when there is a definite need
for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a
closed space or organ, persistent bleeding despite local haemostatic measures,
and need for urgent interventions and/or interventions that carry a high risk for
bleeding), when reversal agents may be helpful, and when a reversal agent is
generally not needed. Key stakeholders who require 24-7/around-the-clock access
to these agents vary among hospitals; however, from a practical perspective the
emergency department is recommended as an appropriate location for these agents.
Clearly, the advent of new agents requires standardised protocols for treating
bleeding on an institutional level.
PMID- 27488233
TI - Trends in racial/ethnic and income disparities in foods and beverages consumed
and purchased from stores among US households with children, 2000-2013.
AB - BACKGROUND: It is unclear whether racial/ethnic and income differences in foods
and beverages obtained from stores contribute to disparities in caloric intake
over time. OBJECTIVE: We sought to determine whether there are disparities in
calories obtained from store-bought consumer packaged goods (CPGs), whether
brands (name brands compared with private labels) matter, and if disparities have
changed over time. DESIGN: We used NHANES individual dietary intake data among
households with children along with the Nielsen Homescan data on CPG purchases
among households with children. With NHANES, we compared survey-weighted energy
intakes for 2003-2006 and 2009-2012 from store and nonstore sources by
race/ethnicity [non-Hispanic whites (NHWs), non-Hispanic blacks (NHBs), and
Hispanic Mexican-Americans) and income [<=185% federal poverty line (FPL), 186
400% FPL, and >400% FPL]. With the Nielsen data, we compared 2000-2013 trends in
calories purchased from CPGs (obtained from stores) across brands by
race/ethnicity (NHW, NHB, and Hispanic) and income. We conducted random-effect
models to derive adjusted trends and differences in calories purchased (708,175
observations from 64,709 unique households) and tested whether trends were
heterogeneous by race/ethnicity or income. RESULTS: Store-bought foods and
beverages represented the largest component of dietary intake, with greater
decreases in energy intakes in nonstore sources for foods and in store sources
for beverages. Beverages from stores consistently decreased in all
subpopulations. However, in adjusted models, reductions in CPG calories purchased
in 2009-2012 were slower for NHB and low-income households than for NHW and high
income households, respectively. The decline in calories from name-brand food
purchases was slower among NHB, Hispanic, and lowest-income households. NHW and
high-income households had the highest absolute calories purchased in 2000.
CONCLUSIONS: Across 2 large data sources, we found decreases in intake and
purchases of beverages from stores across racial/ethnic and income groups.
However, potentially beneficial reductions in calories purchased were more
pronounced in some subgroups over others.
PMID- 27488234
TI - Higher concentrations of serum iron and transferrin saturation but not serum
ferritin are associated with cancer outcomes.
AB - BACKGROUND: Although the carcinogenic potential of iron has been shown, evidence
from observational studies that have linked serum iron variables and cancer
outcomes has been inconsistent. OBJECTIVE: We investigated whether higher iron
concentrations increased risk of cancer outcomes. DESIGN: A prospective
examination of iron biomarkers as independent risk factors for cancer was
assessed in 1597 men and 1795 women aged 25-79 y who participated in the
1994/1995 Busselton Health Survey and had relevant data, no history of cancer
before the survey, and serum ferritin concentrations >=20 MUg/L. Follow-up for
incident cancers and death from cancer was available to 2010. Proportional
hazards regression modeling was performed to investigate if iron status predicted
cancer incidence and mortality. RESULTS: After adjustments for age, smoking,
drinking, anthropometric and biochemical variables, or menopausal status (breast
cancer), higher serum iron concentrations and transferrin saturation were
associated with increased risks of incident nonskin cancer [HR for iron: 1.83
(95% CI: 1.21, 2.76; P < 0.01); HR for transferrin saturation: 1.68 (95% CI:
1.18, 2.38; P < 0.01)] including breast cancer [HR for iron: 2.45 (95% CI:1.12,
5.34; P < 0.05); HR for transferrin saturation: 1.90 (95% CI:1.02, 3.56; P <
0.05)] in women. Transferrin saturation was also associated with a greater risk
of cancer death (HR: 2.48; 95% CI: 1.28, 4.82; P < 0.01). In men, higher iron
concentrations were associated with reduced risks of incident nonskin cancer (HR:
0.65; 95% CI: 0.42, 0.99; P < 0.05) including colorectal cancer (HR: 0.34; 95%
CI: 0.12, 0.95; P < 0.05). There was no association between serum iron and
colorectal cancer risk in women. Serum ferritin was not associated with cancer
risk or cancer death. CONCLUSIONS: Higher transferrin saturation or serum iron
concentrations were associated with increased nonskin cancer risk and increased
risk of cancer death. Conversely, in men, higher serum iron concentrations were
associated with decreased risk of nonskin cancer. The molecular basis for the
observed differences in the association between serum iron and nonskin cancer
risk is unclear.
PMID- 27488235
TI - Biomarkers of browning of white adipose tissue and their regulation during
exercise- and diet-induced weight loss.
AB - BACKGROUND: A hypothesis exists whereby an exercise- or dietary-induced negative
energy balance reduces human subcutaneous white adipose tissue (scWAT) mass
through the formation of brown-like adipocyte (brite) cells. However, the
validity of biomarkers of brite formation has not been robustly evaluated in
humans, and clinical data that link brite formation and weight loss are sparse.
OBJECTIVES: We used rosiglitazone and primary adipocytes to stringently evaluate
a set of biomarkers for brite formation and determined whether the expression of
biomarker genes in scWAT could explain the change in body composition in response
to exercise training combined with calorie restriction in obese and overweight
women (n = 79). DESIGN: Gene expression was derived from exon DNA microarrays and
preadipocytes from obesity-resistant and -sensitive mice treated with
rosiglitazone to generate candidate brite biomarkers from a microarray. These
biomarkers were evaluated against data derived from scWAT RNA from obese and
overweight women before and after supervised exercise 5 d/wk for 16 wk combined
with modest calorie restriction (~0.84 MJ/d). RESULTS: Forty percent of commonly
used brite gene biomarkers exhibited an exon or strain-specific regulation. No
biomarkers were positively related to weight loss in human scWAT. Greater weight
loss was significantly associated with less uncoupling protein 1 expression (P =
0.006, R(2) = 0.09). In a follow-up global analysis, there were 161 genes that
covaried with weight loss that were linked to greater CCAAT/enhancer binding
protein alpha activity (z = 2.0, P = 6.6 * 10(-7)), liver X receptor alpha/beta
agonism (z = 2.1, P = 2.8 * 10(-7)), and inhibition of leptin-like signaling (z =
-2.6, P = 3.9 * 10(-5)). CONCLUSION: We identify a subset of robust RNA
biomarkers for brite formation and show that calorie-restriction-mediated weight
loss in women dynamically remodels scWAT to take on a more-white rather than a
more-brown adipocyte phenotype.
PMID- 27488236
TI - Vitamin D-enhanced eggs are protective of wintertime serum 25-hydroxyvitamin D in
a randomized controlled trial of adults.
AB - BACKGROUND: Despite numerous animal studies that have illustrated the impact of
additional vitamin D in the diet of hens on the resulting egg vitamin D content,
the effect of the consumption of such eggs on vitamin D status of healthy
individuals has not, to our knowledge, been tested. OBJECTIVE: We performed a
randomized controlled trial (RCT) to investigate the effect of the consumption of
vitamin D-enhanced eggs (produced by feeding hens at the maximum concentration of
vitamin D3 or serum 25-hydroxyvitamin D [25(OH)D3] lawfully allowed in feed) on
winter serum 25(OH)D in healthy adults. DESIGN: We conducted an 8-wk winter RCT
in adults aged 45-70 y (n = 55) who were stratified into 3 groups and were
requested to consume <=2 eggs/wk (control group, in which status was expected to
decline), 7 vitamin D3-enhanced eggs/wk, or seven 25(OH)D3-enhanced eggs/wk.
Serum 25(OH)D was the primary outcome. RESULTS: Although there was no significant
difference (P > 0.1; ANOVA) in the mean preintervention serum 25(OH)D in the 3
groups, it was ~7-8 nmol/L lower in the control group than in the 2 groups who
consumed vitamin D-enhanced eggs. With the use of an ANCOVA, in which baseline
25(OH)D was accounted for, vitamin D3-egg and 25(OH)D3-egg groups were shown to
have had significantly higher (P <= 0.005) postintervention serum 25(OH)D than in
the control group. With the use of a within-group analysis, it was shown that,
although serum 25(OH)D in the control group significantly decreased over winter
(mean +/- SD: -6.4 +/- 6.7 nmol/L; P = 0.001), there was no change in the 2
groups who consumed vitamin D-enhanced eggs (P > 0.1 for both). CONCLUSION:
Weekly consumption of 7 vitamin D-enhanced eggs has an important impact on winter
vitamin D status in adults. This trial was registered at clinicaltrials.gov as
NCT02678364.
PMID- 27488237
TI - Habitual intake of anthocyanins and flavanones and risk of cardiovascular disease
in men.
AB - BACKGROUND: Although increased fruit intake reduces cardiovascular disease (CVD)
risk, which fruits are most beneficial and what key constituents are responsible
are unclear. Habitual intakes of flavonoids, specifically anthocyanins and
flavanones, in which >90% of habitual intake is derived from fruit, are
associated with decreased CVD risk in women, but associations in men are largely
unknown. OBJECTIVE: We examined the relation between habitual anthocyanin and
flavanone intake and coronary artery disease and stroke in the Health
Professionals Follow-Up Study. DESIGN: We followed 43,880 healthy men who had no
prior diagnosed CVD or cancer. Flavonoid intake was calculated with the use of
validated food-frequency questionnaires. RESULTS: During 24 y of follow-up, 4046
myocardial infarction (MI) and 1572 stroke cases were confirmed by medical
records. Although higher anthocyanin intake was not associated with total or
fatal MI risk, after multivariate adjustment an inverse association with nonfatal
MI was observed (HR: 0.87; 95% CI: 0.75, 1.00; P = 0.04; P-trend = 0.098); this
association was stronger in normotensive participants (HR: 0.81; 95% CI: 0.69,
0.96; P-interaction = 0.03). Anthocyanin intake was not associated with stroke
risk. Although flavanone intake was not associated with MI or total stroke risk,
higher intake was associated with a lower risk of ischemic stroke (HR: 0.78; 95%
CI: 0.62, 0.97; P = 0.03, P-trend = 0.059), with the greatest magnitude in
participants aged >=65 y (P-interaction = 0.04). CONCLUSIONS: Higher intakes of
fruit-based flavonoids were associated with a lower risk of nonfatal MI and
ischemic stroke in men. Mechanistic studies and clinical trials are needed to
unravel the differential benefits of anthocyanin- and flavanone-rich foods on
cardiovascular health.
PMID- 27488239
TI - Adherence to the cancer prevention recommendations of the World Cancer Research
Fund/American Institute for Cancer Research and mortality: a census-linked
cohort.
AB - BACKGROUND: Modifiable lifestyle factors linked to cancer offer great potential
for prevention. Previous studies suggest an association between adherence to
recommendations on healthy lifestyle and cancer mortality. OBJECTIVES: The aim of
this study was to examine whether adherence to the cancer prevention
recommendations of the World Cancer Research Fund (WCRF) and the American
Institute for Cancer Research (AICR) is associated with reduced all-cause, total
cancer, and specific cancer type mortality. DESIGN: We built a lifestyle score
that included 3 categories, based on the recommendations of the WCRF/AICR.
Applying Cox regression models, we investigated the association with all-cause,
total cancer, and specific cancer type mortality; in addition, we included
cardiovascular disease (CVD) mortality. We used census- and death registry-linked
survey data allowing a mortality follow-up for <=32 y. Our analysis included
16,722 participants. Information on lifestyle score components and confounders
was collected at baseline. RESULTS: Over a mean follow-up of 21.7 y, 3730 deaths
were observed (1332 cancer deaths). Comparing best with poorest category of the
lifestyle score showed an inverse association with all-cause (HR: 0.82; 95% CI:
0.75, 0.89) and total cancer (men only, HR: 0.69; 95% CI: 0.57, 0.84) mortality.
We estimated that ~13% of premature cancer deaths in men would have been
preventable if lifestyle score levels had been high. Inverse associations were
observed for lung, upper aerodigestive tract, stomach, and prostate cancer
mortality [men and women combined, HR: 0.72; 95% CI: 0.51, 0.99; HR: 0.49; 95%
CI: 0.26, 0.92; HR: 0.34; 95% CI: 0.14, 0.83; HR: 0.48; 95% CI: 0.28, 0.82 (men
only), respectively]. CVD mortality was not associated with the lifestyle score
(men and women combined, HR: 0.96; 95% CI: 0.82, 1.13). CONCLUSIONS: Our results
support the importance of adhering to recommendations for a healthy lifestyle
with regard to all-cause and cancer mortality. To reduce the burden of cancer in
the population, preventive measures should stress the potential of low-risk
health behavior patterns rather than of specific risk factors only.
PMID- 27488238
TI - Mediterranean diet score and left ventricular structure and function: the Multi
Ethnic Study of Atherosclerosis.
AB - BACKGROUND: Data are limited on the relation between dietary patterns and left
ventricular (LV) structure and function. OBJECTIVE: We examined cross-sectional
associations of a diet-score assessment of a Mediterranean dietary pattern with
LV mass, volume, mass-to-volume ratio, stroke volume, and ejection fraction.
DESIGN: We measured LV variables with the use of cardiac MRI in 4497 participants
in the Multi-Ethnic Study of Atherosclerosis study who were aged 45-84 y and
without clinical cardiovascular disease. We calculated a Mediterranean diet score
from intakes of fruit, vegetables, nuts, legumes, whole grains, fish, red meat,
the monounsaturated fat:saturated fat ratio, and alcohol that were self-reported
with the use of a food-frequency questionnaire. We used linear regression with
adjustment for body size, physical activity, and cardiovascular disease risk
factors to model associations and assess the shape of these associations (linear
or quadratic). RESULTS: The Mediterranean diet score had a slight U-shaped
association with LV mass (adjusted means: 146, 145, 146, and 147 g across
quartiles of diet score, respectively; P-quadratic trend = 0.04). The score was
linearly associated with LV volume, stroke volume, and ejection fraction: for
each +1-U difference in score, LV volume was 0.4 mL higher (95% CI: 0.0, 0.8 mL
higher), the stroke volume was 0.5 mL higher (95% CI: 0.2, 0.8 mL higher), and
the ejection fraction was 0.2 percentage points higher (95% CI: 0.1, 0.3
percentage points higher). The score was not associated with the mass-to-volume
ratio. CONCLUSIONS: A higher Mediterranean diet score is cross-sectionally
associated with a higher LV mass, which is balanced by a higher LV volume as well
as a higher ejection fraction and stroke volume. Participants in this healthy,
multiethnic sample whose dietary patterns most closely conformed to a
Mediterranean-type pattern had a modestly better LV structure and function than
did participants with less-Mediterranean-like dietary patterns. This trial was
registered at clinicaltrials.gov as NCT00005487.
PMID- 27488241
TI - Exploring the mechanism of DNA polymerases by analyzing the effect of mutations
of active site acidic groups in Polymerase beta.
AB - Elucidating the catalytic mechanism of DNA polymerase is crucial for a progress
in the understanding of the control of replication fidelity. This work tries to
advance the mechanistic understanding by analyzing the observed effect of
mutations of the acidic groups in the active site of Polymerase beta as well as
the pH effect on the rate constant. The analysis involves both empirical valence
bond (EVB) free energy calculations and considerations of the observed pH
dependence of the reaction. The combined analysis indicates that the proton
transfer (PT) from the nucleophilic O3' has two possible pathways, one to D256
and the second to the bulk. We concluded based on calculations and the
experimental pH profile that the most likely path for the wild-type (WT) and the
D256E and D256A mutants is a PT to the bulk, although the WT may also use a PT to
Asp 256. Our analysis highlights the need for very extensive sampling in the
calculations of the activation barrier and also clearly shows that ab initio
QM/MM calculations that do not involve extensive sampling are unlikely to give a
clear quantitative picture of the reaction mechanism. Proteins 2016; 84:1644
1657. (c) 2016 Wiley Periodicals, Inc.
PMID- 27488240
TI - Predominant expression of Alzheimer's disease-associated BIN1 in mature
oligodendrocytes and localization to white matter tracts.
AB - BACKGROUND: Genome-wide association studies have identified BIN1 within the
second most significant susceptibility locus in late-onset Alzheimer's disease
(AD). BIN1 undergoes complex alternative splicing to generate multiple isoforms
with diverse functions in multiple cellular processes including endocytosis and
membrane remodeling. An increase in BIN1 expression in AD and an interaction
between BIN1 and Tau have been reported. However, disparate descriptions of BIN1
expression and localization in the brain previously reported in the literature
and the lack of clarity on brain BIN1 isoforms present formidable challenges to
our understanding of how genetic variants in BIN1 increase the risk for AD.
METHODS: In this study, we analyzed BIN1 mRNA and protein levels in human brain
samples from individuals with or without AD. In addition, we characterized the
BIN1 expression and isoform diversity in human and rodent tissue by
immunohistochemistry and immunoblotting using a panel of BIN1 antibodies.
RESULTS: Here, we report on BIN1 isoform diversity in the human brain and
document alterations in the levels of select BIN1 isoforms in individuals with
AD. In addition, we report striking BIN1 localization to white matter tracts in
rodent and the human brain, and document that the large majority of BIN1 is
expressed in mature oligodendrocytes whereas neuronal BIN1 represents a minor
fraction. This predominant non-neuronal BIN1 localization contrasts with the
strict neuronal expression and presynaptic localization of the BIN1 paralog,
Amphiphysin 1. We also observe upregulation of BIN1 at the onset of postnatal
myelination in the brain and during differentiation of cultured oligodendrocytes.
Finally, we document that the loss of BIN1 significantly correlates with the
extent of demyelination in multiple sclerosis lesions. CONCLUSION: Our study
provides new insights into the brain distribution and cellular expression of an
important risk factor associated with late-onset AD. We propose that efforts to
define how genetic variants in BIN1 elevate the risk for AD would behoove to
consider BIN1 function in the context of its main expression in mature
oligodendrocytes and the potential for a role of BIN1 in the membrane remodeling
that accompanies the process of myelination.
PMID- 27488242
TI - First genetic linkage map of Taraxacum koksaghyz Rodin based on AFLP, SSR, COS
and EST-SSR markers.
AB - Taraxacum koksaghyz Rodin (TKS) has been studied in many occasions as a possible
alternative source for natural rubber production of good quality and for inulin
production. Some tire companies are already testing TKS tire prototypes. There
are also many investigations on the production of bio-fuels from inulin and
inulin applications for health improvement and in the food industry. A limited
amount of genomic resources exist for TKS and particularly no genetic linkage map
is available in this species. We have constructed the first TKS genetic linkage
map based on AFLP, COS, SSR and EST-SSR markers. The integrated linkage map with
eight linkage groups (LG), representing the eight chromosomes of Russian
dandelion, has 185 individual AFLP markers from parent 1, 188 individual AFLP
markers from parent 2, 75 common AFLP markers and 6 COS, 1 SSR and 63 EST-SSR
loci. Blasting the EST-SSR sequences against known sequences from lettuce allowed
a partial alignment of our TKS map with a lettuce map. Blast searches against
plant gene databases revealed some homologies with useful genes for downstream
applications in the future.
PMID- 27488243
TI - Suspicion in the workplace: Organizational conspiracy theories and work-related
outcomes.
AB - Belief in conspiracy theories about societal events is widespread and has
important consequences for political, health, and environmental behaviour. Little
is known, however, about how conspiracy theorizing affects people's everyday
working lives. In the present research, we predicted that belief in conspiracy
theories about the workplace would be associated with increased turnover
intentions. We further hypothesized that belief in these organizational
conspiracy theories would predict decreased organizational commitment and job
satisfaction. Finally, we hypothesized that these factors would mediate the
relationship between organizational conspiracy theories and turnover intentions.
In three studies (one correlational and two experiments, Ns = 209, 119, 202), we
found support for these hypotheses. The current studies therefore demonstrate the
potentially adverse consequences of conspiracy theorizing for the workplace. We
argue that managers and employees should be careful not to dismiss conspiracy
theorizing as harmless rumour or gossip.
PMID- 27488245
TI - Protistan predation interferes with bacterial long-term adaptation to substrate
restriction by selecting for defence morphotypes.
AB - Bacteria that are introduced into aquatic habitats face a low substrate
environment interspersed with rare productive 'hotspots', as well as high
protistan grazing. Whereas the former condition should select for growth
performance, the latter should favour traits that reduce predation mortality,
such as the formation of large cell aggregates. However, protected morphotypes
often convey a growth disadvantage, and bacteria thus face a trade-off between
investing in growth or defence traits. We set up an evolutionary experiment with
the freshwater isolate Sphingobium sp. strain Z007 that conditionally increases
aggregate formation in supernatants from a predator-prey coculture. We
hypothesized that low substrate levels would favour growth performance and reduce
the aggregated subpopulation, but that the concomitant presence of a flagellate
predator might conserve the defence trait. After 26 (1-week) growth cycles either
with (P+) or without (P-) predators, bacteria had evolved into strikingly
different phenotypes. Strains from P- had low numbers of aggregates and increased
growth yield, both at the original rich growth conditions and on various single
carbon sources. By contrast, isolates from the P+ treatment formed elevated
proportions of defence morphotypes, but exhibited lower growth yield and
metabolic versatility. Moreover, the evolved strains from both treatments had
lost phenotypic plasticity of aggregate formation. In summary, the (transient)
residence of bacteria at oligotrophic conditions may promote a facultative
oligotrophic life style, which is advantageous for survival in aquatic habitats.
However, the investment in defence against predation mortality may constrain
microbial adaptation to the abiotic environment.
PMID- 27488244
TI - Activation of sigma1 and sigma2 receptors by afobazole increases glial cell
survival and prevents glial cell activation and nitrosative stress after ischemic
stroke.
AB - Activation of sigma receptors at delayed time points has been shown to decrease
injury following ischemic stroke. The mixed sigma1/sigma2 receptor agonist, 5
ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole (afobazole), provides superior
long-term outcomes compared to other sigma ligands in the rat middle cerebral
artery occlusion (MCAO) stroke model. Experiments using the MCAO model were
carried out to determine the molecular mechanism involved in the beneficial
effects of afobazole. Administration of afobazole (3 mg/kg) at delayed time
points post-stroke significantly increased the number of microglia and astrocytes
detected in the ipsilateral hemisphere at 96 h post-surgery. Morphological
analysis of the microglia indicated that a greater number of these cells were
found in the ramified resting state in MCAO animals treated with afobazole
relative to MCAO vehicle controls. Similarly, fewer reactive astrocytes were
detected in the injured hemisphere of afobazole-treated animals. Both the
enhanced survival and reduced activation of glial cells were abolished by co
application of either a sigma1 (BD-1063) or a sigma2 (SM-21) receptor antagonist
with afobazole. To gain further insight into the mechanisms by which afobazole
lessens stroke injury, we probed the brain sections for markers of
neuroinflammation (tumor necrosis factor alpha) and nitrosative stress (S
nitrosocysteine). Data show that afobazole significantly reduces S
nitrosocysteine levels, but does not alter tumor necrosis factor alpha expression
96 h after an ischemic stroke. Taken together our data indicate that afobazole
acting via both sigma1 and sigma2 receptors decreases stroke injury by enhancing
glial cell survival, blocking ischemia-induced glial cell activation, and
decreasing nitrosative stress.
PMID- 27488247
TI - Unique molecular geometries of reduced 4- and 5-coordinate zinc complexes
stabilised by diiminopyridine ligand.
AB - Stepwise reduction of the diiminopyridine (dimpyr) complex, dimpyrZnCl2, by KC8
leads to molecular zinc compounds dimpyrZnCl (2) and dimpyrZnCl(DMAP) (3, DMAP =
4-dimethylaminopyridine), which were characterized by X-ray diffraction and EPR
spectroscopy. Compound 2 shows an unusual nearly square planar geometry of the
zinc atom equally ligated by two imine groups. X-ray crystallographic and EPR
data suggest significant delocalization of the zinc 4p electron onto the non
innocent dimpyr ligand. The chloride in 2 can also be substituted by a methyl
group upon addition of methyl lithium to generate compound 4, dimpyrZnMe. The
novel alkylzinc compound displayed approximate square planar geometry around the
zinc centre and significant delocalization of electron density onto the dimpyr
ligand, as revealed by X-ray crystallographic studies and EPR spectroscopy, akin
to 2. Further reduction of 3 leads to compound 5, dimpyrZn(DMAP)2. X-ray
diffraction study of 5 revealed an unprecedented see-saw geometry around the four
coordinate zinc center with significant electron density transfer to the dimpyr
ligand, supported by DFT calculations.
PMID- 27488246
TI - The combination of dulaglutide and biguanide reduced bodyweight in Japanese
patients with type 2 diabetes.
AB - The efficacy and safety of once-weekly dulaglutide 0.75 mg (dulaglutide) in
Japanese patients with type 2 diabetes (T2D) were evaluated according to
subgroups defined by concomitant oral hypoglycaemic agents. This exploratory
analysis included data from a randomized, open-label, phase III study that
compared dulaglutide with insulin glargine (glargine) (n = 361). The three
subgroups were dulaglutide or glargine in combination with sulphonylurea (SU)
alone, biguanide (BG) alone or SU and BG combined. There were no clinically
relevant differences in glycated haemoglobin (HbA1c) changes among the three
subgroups in the dulaglutide group; in the glargine group, a numerically greater
reduction was observed in combination with BG alone compared to the other two
groups (SU alone and SU + BG). Weight loss was observed with dulaglutide in
combination with BG alone or with SU + BG. The incidence of adverse events among
subgroups was significantly different in the glargine group but not in the
dulaglutide group. Incidence of hypoglycaemia was highest in combination with SU
for both treatments. For patients with T2D, dulaglutide added to concomitant BG
may be more likely to result in weight loss than dulaglutide added to concomitant
SU.
PMID- 27488248
TI - A comparative assessment of SNP and microsatellite markers for assigning
parentage in a socially monogamous bird.
AB - Single-nucleotide polymorphisms (SNPs) are preferred over microsatellite markers
in many evolutionary studies, but have only recently been applied to studies of
parentage. Evaluations of SNPs and microsatellites for assigning parentage have
mostly focused on special cases that require a relatively large number of
heterozygous loci, such as species with low genetic diversity or with complex
social structures. We developed 120 SNP markers from a transcriptome assembled
using RNA-sequencing of a songbird with the most common avian mating system
social monogamy. We compared the effectiveness of 97 novel SNPs and six
previously described microsatellites for assigning paternity in the black
throated blue warbler, Setophaga caerulescens. We show that the full panel of 97
SNPs (mean Ho = 0.19) was as powerful for assigning paternity as the panel of
multiallelic microsatellites (mean Ho = 0.86). Paternity assignments using the
two marker types were in agreement for 92% of the offspring. Filtering individual
samples by a 50% call rate and SNPs by a 75% call rate maximized the number of
offspring assigned with 95% confidence using SNPs. We also found that the 40 most
heterozygous SNPs (mean Ho = 0.37) had similar power to assign paternity as the
full panel of 97 SNPs. These findings demonstrate that a relatively small number
of variable SNPs can be effective for parentage analyses in a socially monogamous
species. We suggest that the development of SNP markers is advantageous for
studies that require high-throughput genotyping or that plan to address a range
of ecological and evolutionary questions.
PMID- 27488249
TI - Evaluating empirical contact networks as potential transmission pathways for
infectious diseases.
AB - Networks are often used to incorporate heterogeneity in contact patterns in
mathematical models of pathogen spread. However, few tools exist to evaluate
whether potential transmission pathways in a population are adequately
represented by an observed contact network. Here, we describe a novel permutation
based approach, the network k-test, to determine whether the pattern of cases
within the observed contact network are likely to have resulted from transmission
processes in the network, indicating that the network represents potential
transmission pathways between nodes. Using simulated data of pathogen spread, we
compare the power of this approach to other commonly used analytical methods. We
test the robustness of this technique across common sampling constraints,
including undetected cases, unobserved individuals and missing interaction data.
We also demonstrate the application of this technique in two case studies of
livestock and wildlife networks. We show that the power of the k-test to
correctly identify the epidemiologic relevance of contact networks is
substantially greater than other methods, even when 50% of contact or case data
are missing. We further demonstrate that the impact of missing data on network
analysis depends on the structure of the network and the type of missing data.
PMID- 27488250
TI - Elasto-capillarity in insect fibrillar adhesion.
AB - The manipulation of microscopic objects is challenging because of high adhesion
forces, which render macroscopic gripping strategies unsuitable. Adhesive
footpads of climbing insects could reveal principles relevant for micro-grippers,
as they are able to attach and detach rapidly during locomotion. However, the
underlying mechanisms are still not fully understood. In this work, we
characterize the geometry and contact formation of the adhesive setae of dock
beetles (Gastrophysa viridula) by interference reflection microscopy. We compare
our experimental results to the model of an elastic beam loaded with capillary
forces. Fitting the model to experimental data yielded not only estimates for
seta adhesion and compliance in agreement with previous direct measurements, but
also previously unknown parameters such as the volume of the fluid meniscus and
the bending stiffness of the tip. In addition to confirming the primary role of
surface tension for insect adhesion, our investigation reveals marked differences
in geometry and compliance between the three main kinds of seta tips in leaf
beetles.
PMID- 27488252
TI - Somatic mosaicism in B cells of a patient with autosomal dominant hyper IgE
syndrome.
AB - Hyper IgE syndrome (HIES) is characterized by recurrent skin abscesses, eczema,
pneumonia, and high levels of serum IgE. Nonimmunologic manifestations of HIES
include a characteristic face, pathologic dentition, scoliosis, bone alterations,
hyperextensible joints, and vascular abnormalities. Somatic mosaicism is defined
by the presence of two or more populations of cells with different genotypes in
one individual. In this report, we describe one patient with classical HIES and
another patient with a mild phenotype, both harboring the same genetic mutation.
The patient with a mild phenotype did not present the characteristic face, had
normal production of IL-17A by T CD4+ cells, but had low phosphorylation of STAT
3 in B cells. Interestingly, the mutation found in B cells was absent in other
cell types analyzed, in agreement with the presence of a somatic mosaic genotype.
The clinical and functional differences observed between these patients justify
the use of complementary tools for a better definition of the cases. These
approaches allow for a better understanding of complex phenotypes associated with
somatic mosaicisms, and present the possibility to analyze the role of B
lymphocytes in the pathophysiology of this disease. This knowledge has an impact
on not only the treatment but also the provision of appropriate genetic
counseling.
PMID- 27488253
TI - Penicillium pedernalense sp. nov., isolated from whiteleg shrimp heads waste
compost.
AB - Novel Penicillium-like strains were isolated during the characterization of the
mycobiota community dynamics associated with shrimp waste composting.
Phylogenetic analysis of the partial beta-tubulin (BenA) gene and the ribosomal
DNA internal transcribed spacer region (ITS1-5.8S-ITS2) sequences revealed that
the novel strains were members of section Lanata-Divaricata and were closely
related to Penicillium infrabuccalum DAOMC 250537T. On the basis of morphological
and physiological characterization, and phylogenetic analysis, a novel
Penicillium species, Penicillium pedernalense sp. nov., is proposed. The type
strain is F01-11T (=CBS 140770T=CECT 20949T), which was isolated from whiteleg
shrimp (Litopenaeus vannamei) heads waste compost in the Pedernales region
(Manabi province, Ecuador).
PMID- 27488254
TI - Effects of ankyrin 3 gene risk variants on brain structures in patients with
bipolar disorder and healthy subjects.
AB - AIM: The intronic single-nucleotide polymorphism rs10994336 of the ankyrin 3 gene
(ANK3 ) is one of the genome-wide supported risk variants for bipolar disorder
(BD), and the T-allele of rs10761482 is also reported to have relevance to BD. We
investigated the effect of ANK3 rs10761482 genetic variation on brain structure.
METHODS: Subjects were 43 BD patients and 229 healthy volunteers. We evaluated
the effects of ANK3 rs10761482 genetic variation on diagnosis, and of the
genotype-by-diagnosis interaction on the brain structure and the degree of age
related brain atrophy on magnetic resonance imaging data evaluated by voxel-based
morphometry. RESULTS: BD patients showed significantly lower fractional
anisotropy value in the bilateral parietal regions, left fronto-occipital
fasciculus, and corpus callosum, compared to healthy subjects. Further, we found
considerable decreases of fractional anisotropy in the forceps minor in non-T
allele BD patients compared with the T-carrier patient group. We also found
significant lessening of age-related brain atrophy in the T-allele carrier groups
compared with the non-T-allele carrier groups in the area around the
cerebrospinal space, cingulate cortices, and cerebellum. CONCLUSION: Our results
suggest the influence of the ANK3 on age-related brain atrophy. The ankyrin 3
genotype may be associated with pathogenesis of age-related neurodegeneration,
and, in part, of BD.
PMID- 27488255
TI - Exploring the relationship between physical activity, life goals and health
related quality of life among high school students: a cross-sectional study.
AB - BACKGROUND: Two models were developed to increase high school students'
participation in physical education (PE): "motion enjoyment" and "sport
enjoyment". The first model focuses on increasing knowledge about the health
benefits of a physically active lifestyle and thereby promoting a positive
attitude towards physical activity, whereas the second model focuses on
techniques and practices for enhancing athletic performance. The aims of the
present study are to investigate and understand the similarities and differences
between students selecting "motion enjoyment" vs. "sport enjoyment" and to
examine the extent to which life goals and reported physical activity are
associated with health-related quality of life (HRQOL). METHOD: A total of 156
high school students (mean age, 16 years [standard deviation = 0.8], 123 girls
and 33 boys) were included in this cross-sectional study. HRQOL and life goals
were measured using KIDSCREEN-10 and the Adolescent Life Goal Profile Scale,
respectively. Physical activity was measured using a self-reporting questionnaire
intended to describe the students' leisure-time activity. Independent sample t
tests, chi-square, one-way analyses of variance and multiple regression analysis
were applied. RESULTS: Self-reported physical activity level and HRQOL were
higher among students in the "sport enjoyment" program, while the perceived
importance of life goals was the same regardless of the preferred PE model.
Multiple regression analyses revealed that the perceived importance of relations
oriented life goals (B = -5.61; 95 % confidence interval CI = -10.53 to -0.70; p
= .026), perceived importance of generativity-oriented life goals (B = 4.14.; 95
% CI = 0.85 to 7.422; p = .014), perceived attainability of relations-oriented
life goals (B = 7.28; 95 % CI = 2.49 to 12.07; p = .003), age (B = -7.29; 95 % CI
= -11.38 to -3.20; p = .001) and gender, with boys as the reference group (B =
12.10; 95 % CI = -19.09 to -5.11; p = .001), were independently associated with
increased HRQOL. In exploring the relationships of self-reported physical
activity during leisure time, stage of change (B = 3.53; 95 % CI = 1.49 to 5.51;
p = .001), gender, with boys as the reference group (B = -8.90; 95 % CI = -15.80
to -2.00; p = .012), and age (B = -6.62; 95 % CI = -10.57 to -2.66; p = .001)
were independently associated with increased HRQOL. CONCLUSION: Self-reported
physical activity habits and life goals were associated with HRQOL to a limited
extent. However, the perceived importance of life goals appears to reflect other
aspects of individual well-being than HRQOL.
PMID- 27488256
TI - Automated statistical experimental design approach for rapid separation of
coenzyme Q10 and identification of its biotechnological process related
impurities using UHPLC and UHPLC-APCI-MS.
AB - A novel ultra high performance liquid chromatography method development strategy
was ameliorated by applying quality by design approach. The developed systematic
approach was divided into five steps (i) Analytical Target Profile, (ii) Critical
Quality Attributes, (iii) Risk Assessments of Critical parameters using design of
experiments (screening and optimization phases), (iv) Generation of design space,
and (v) Process Capability Analysis (Cp) for robustness study using Monte Carlo
simulation. The complete quality-by-design-based method development was made
automated and expedited by employing sub-2 MUm particles column with an ultra
high performance liquid chromatography system. Successful chromatographic
separation of the Coenzyme Q10 from its biotechnological process related
impurities was achieved on a Waters Acquity phenyl hexyl (100 mm * 2.1 mm, 1.7
MUm) column with gradient elution of 10 mM ammonium acetate buffer (pH 4.0) and a
mixture of acetonitrile/2-propanol (1:1) as the mobile phase. Through this study,
fast and organized method development workflow was developed and robustness of
the method was also demonstrated. The method was validated for specificity,
linearity, accuracy, precision, and robustness in compliance to the International
Conference on Harmonization, Q2 (R1) guidelines. The impurities were identified
by atmospheric pressure chemical ionization-mass spectrometry technique. Further,
the in silico toxicity of impurities was analyzed using TOPKAT and DEREK
software.
PMID- 27488258
TI - A literature review of the training offered to qualified prescribers to use
electronic prescribing systems: why is it so important?
AB - OBJECTIVES: A key element of the implementation and ongoing use of an electronic
prescribing (ePrescribing) system is ensuring that users are, and remain,
sufficiently trained to use the system. Studies have suggested that insufficient
training is associated with suboptimal use. However, it is not clear from these
studies how clinicians are trained to use ePrescribing systems or the
effectiveness of different approaches. We sought to describe the various
approaches used to train qualified prescribers on ePrescribing systems and to
identify whether users were educated about the pitfalls and challenges of using
these systems. METHODS: We performed a literature review, using a systematic
approach across three large databases: Cumulative Index Nursing and Allied Health
Literature, Embase and Medline were searched for relevant English language
articles. Articles that explored the training of qualified prescribers on
ePrescribing systems in a hospital setting were included. KEY FINDINGS: Our
search of 'all training' approaches returned 1155 publications, of which seven
were included. A separate search of 'online' training found three relevant
publications. Training methods in the 'all training' category included clinical
scenarios, demonstrations and assessments. Regarding 'online' training
approaches; a team at the University of Victoria in Canada developed a portal
containing simulated versions of electronic health records, where individuals
could prescribe for fictitious patients. Educating prescribers about the
challenges and pitfalls of electronic systems was rarely discussed. CONCLUSIONS:
A number of methods are used to train prescribers; however, the lack of papers
retrieved suggests a need for additional studies to inform training methods.
PMID- 27488259
TI - Near-peer medical student simulation training.
AB - BACKGROUND: There is growing concern that medical students are inadequately
prepared for life as a junior doctor. A lack of confidence managing acutely
unwell patients is often cited as a barrier to good clinical care. With medical
schools investing heavily in simulation equipment, we set out to explore if near
peer simulation training is an effective teaching format. METHODS: Medical
students in their third year of study and above were invited to attend a 90
minute simulation teaching session. The sessions were designed and delivered by
final-year medical students using clinical scenarios mapped to the Sheffield
MBChB curriculum. Candidates were required to assess, investigate and manage an
acutely unwell simulated patient. Pre- and post-simulation training Likert scale
questionnaires were completed relating to self-reported confidence levels. There
is growing concern that medical students are inadequately prepared for life as a
junior doctor RESULTS: Questionnaires were completed by 25 students (100%
response rate); 52 per cent of students had no prior simulation experience. There
were statistically significant improvements in self-reported confidence levels in
each of the six areas assessed (p < 0.005). Thematic analysis of free-text
comments indicated that candidates enjoyed the practical format of the sessions
and found the experience useful. DISCUSSION: Our results suggest that near-peer
medical student simulation training benefits both teacher and learner and that
this simplistic model could easily be replicated at other medical schools. As the
most junior members of the team, medical students are often confined to observer
status. Simulation empowers students to practise independently in a safe and
protected environment. Furthermore, it may help to alleviate anxiety about
starting work as a junior doctor and improve future patient care.
PMID- 27488257
TI - Genome comparisons provide insights into the role of secondary metabolites in the
pathogenic phase of the Photorhabdus life cycle.
AB - BACKGROUND: Bacteria within the genus Photorhabdus maintain mutualistic symbioses
with nematodes in complicated lifecycles that also involves insect pathogenic
phases. Intriguingly, these bacteria are rich in biosynthetic gene clusters that
produce compounds with diverse biological activities. As a basis to better
understand the life cycles of Photorhabdus we sequenced the genomes of two
recently discovered representative species and performed detailed genomic
comparisons with five publically available genomes. RESULTS: Here we report the
genomic details of two new reference Photorhabdus species. By then conducting
genomic comparisons across the genus, we show that there are several highly
conserved biosynthetic gene clusters. These clusters produce a range of bioactive
small molecules that support the pathogenic phase of the integral relationship
that Photorhabdus maintain with nematodes. CONCLUSIONS: Photorhabdus contain
several genetic loci that allow them to become specialist insect pathogens by
efficiently evading insect immune responses and killing the insect host.
PMID- 27488260
TI - Dietary choline and betaine intake, choline-metabolising genetic polymorphisms
and breast cancer risk: a case-control study in China.
AB - Choline and betaine are essential nutrients involved in one-carbon metabolism and
have been hypothesised to affect breast cancer risk. Functional polymorphisms in
genes encoding choline-related one-carbon metabolism enzymes, including
phosphatidylethanolamine N-methyltransferase (PEMT), choline dehydrogenase (CHDH)
and betaine-homocysteine methyltransferase (BHMT), have important roles in
choline metabolism and may thus interact with dietary choline and betaine intake
to modify breast cancer risk. This study aimed to investigate the interactive
effect of polymorphisms in PEMT, BHMT and CHDH genes with choline/betaine intake
on breast cancer risk among Chinese women. This hospital-based case-control study
consecutively recruited 570 cases with histologically confirmed breast cancer and
576 age-matched (5-year interval) controls. Choline and betaine intakes were
assessed by a validated FFQ, and genotyping was conducted for PEMT rs7946, CHDH
rs9001 and BHMT rs3733890. OR and 95 % CI were estimated using unconditional
logistic regression. Compared with the highest quartile of choline intake, the
lowest intake quartile showed a significant increased risk of breast cancer. The
SNP PEMT rs7946, CHDH rs9001 and BHMT rs3733890 had no overall association with
breast cancer, but a significant risk reduction was observed among postmenopausal
women with AA genotype of BHMT rs3733890 (OR 0.49; 95 % CI 0.25, 0.98).
Significant interactions were observed between choline intake and SNP PEMT rs7946
(P interaction=0.029) and BHMT rs3733890 (P interaction=0.006) in relation to
breast cancer risk. Our results suggest that SNP PEMT rs7946 and BHMT rs3733890
may interact with choline intake on breast cancer risk.
PMID- 27488262
TI - The impact of multiple chronic diseases on hospitalizations for ambulatory care
sensitive conditions.
AB - BACKGROUND: The high financial burden of avoidable hospitalizations has led to an
increase of the study of hospitalizations for ambulatory care sensitive
conditions (ACSC). There is limited information on the impact of secondary
diagnoses on these hospitalizations, although patients' social and demographic
characteristics, as well as the coexistence of multiple diseases are often
identified in the literature as risk factors for avoidable hospitalizations. This
study explores the impact of chronic conditions on the likelihood of
hospitalizations for ACSC. METHODS: Data were extracted from the Portuguese
hospital discharge database. Avoidable hospitalizations were identified according
to the Canadian Institute for Healthcare Information, and chronic conditions were
identified according to criteria set by the Agency for Healthcare Research and
Quality. A retrospective study analysing all patients hospitalized for an ACSC
and all patients hospitalized for non-ACSC was made, using multiple logistic
regression models to identify the impact of chronic conditions on the risk of
admission. RESULTS: The risk of an avoidable hospitalization increases by a
factor of 1.35 (95 % CI [1.34;1.35]) for each additional chronic condition, and
1.55 (95 % CI [1.55;1.56]) for each additional body system affected. The
respiratory and circulatory systems have the most impact on the risk of ACSC,
increasing the risk by 8.72 (95 % CI [8.58;8.86]) and 3.01 (95 % CI [2.95;3.06]),
respectively. CONCLUSIONS: The number of chronic conditions and the body systems
affected increase the risk of hospital admissions for ACSC.
PMID- 27488261
TI - Relaxin serum levels in acute heart failure are associated with pulmonary
hypertension and right heart overload.
AB - AIMS: Despite the promising results of serelaxin as a new potential acute heart
failure (HF) therapy, its clinical use preceded the understanding of the
endogenous relaxin system in HF. We aimed to evaluate relaxin circulating levels
in a population of acute HF and their association with clinical and
echocardiographic parameters. METHODS AND RESULTS: We included 117 patients from
a registry of acute HF. Admission serum relaxin was measured using an enzyme
linked immunosorbent assay (ELISA) kit. Clinical, analytical, and
echocardiographic parameters were compared between patients with relaxin levels
above and below the median. Median age was 82 years [interquartile range (IQR) 72
87], 41% of the patients were male, and 63% had systolic dysfunction. Median
serum relaxin was 31.4 pg/mL (IQR 0.6-89.8). Patients with relaxin levels above
the median had more peripheral oedema (89.8% vs. 68.4%, P = 0.004) and a
significantly higher sodium retention score (mean 4.8 +/- 1.5 vs. 3.6 +/- 2.0, P
< 0.001). These patients also had significantly higher systolic pulmonary
arterial pressure [median 47.0 (IQR 36.0-61.0) vs. 34.5 (IQR 25.0-51.0) mmHg, P =
0.002], higher prevalence of right ventricular (RV) systolic dysfunction (28.1%
vs. 10.3%, P = 0.02), RV dilation (31.0% vs. 5.3%, P < 0.001), and right atrial
dilation (66.1% vs. 36.5%, P = 0.002), and less inferior vena cava diameter
variability (40% vs. 60%, P = 0.009). No differences were noted regarding
admission blood pressure, left chamber dimensions, or LV function. CONCLUSION: In
our population of acute HF patients, admission relaxin serum levels were
associated with clinical and echocardiographic markers of pulmonary hypertension,
RV dysfunction, and overload, suggesting a role for circulating relaxin as a
biomarker in this setting.
PMID- 27488263
TI - Comparison of optomagnetic and AC susceptibility readouts in a magnetic
nanoparticle agglutination assay for detection of C-reactive protein.
AB - There is an increasing need to develop biosensor methods that are highly
sensitive and that can be combined with low-cost consumables. The use of magnetic
nanoparticles (MNPs) is attractive because their detection is compatible with low
cost disposables and because application of a magnetic field can be used to
accelerate assay kinetics. We present the first study and comparison of the
performance of magnetic susceptibility measurements and a newly proposed
optomagnetic method. For the comparison we use the C-reactive protein (CRP)
induced agglutination of identical samples of 100nm MNPs conjugated with CRP
antibodies. Both methods detect agglutination as a shift to lower frequencies in
measurements of the dynamics in response to an applied oscillating magnetic
field. The magnetic susceptibility method probes the magnetic response whereas
the optomagnetic technique probes the modulation of laser light transmitted
through the sample. The two techniques provided highly correlated results upon
agglutination when they measure the decrease of the signal from the individual
MNPs (turn-off detection strategy), whereas the techniques provided different
results, strongly depending on the read-out frequency, when detecting the signal
due to MNP agglomerates (turn-on detection strategy). These observations are
considered to be caused by differences in the volume-dependence of the magnetic
and optical signals from agglomerates. The highest signal from agglomerates was
found in the optomagnetic signal at low frequencies.
PMID- 27488264
TI - An O2-sensing stressosome from a Gram-negative bacterium.
AB - Bacteria have evolved numerous pathways to sense and respond to changing
environmental conditions, including, within Gram-positive bacteria, the
stressosome complex that regulates transcription of general stress response
genes. However, the signalling molecules recognized by Gram-positive stressosomes
have yet to be identified, hindering our understanding of the signal transduction
mechanism within the complex. Furthermore, an analogous pathway has yet to be
described in Gram-negative bacteria. Here we characterize a putative stressosome
from the Gram-negative bacterium Vibrio brasiliensis. The sensor protein RsbR
binds haem and exhibits ligand-dependent control of the stressosome complex
activity. Oxygen binding to the haem decreases activity, while ferrous RsbR
results in increased activity, suggesting that the V. brasiliensis stressosome
may be activated when the bacterium enters anaerobic growth conditions. The
findings provide a model system for investigating ligand-dependent signalling
within stressosome complexes, as well as insights into potential pathways
controlled by oxygen-dependent signalling within Vibrio species.
PMID- 27488265
TI - Molecular Engineering of Potent Sensitizers for Very Efficient Light Harvesting
in Thin-Film Solid-State Dye-Sensitized Solar Cells.
AB - Dye-sensitized solar cells (DSSCs) have shown significant potential for indoor
and building-integrated photovoltaic applications. Herein we present three new D
A-pi-A organic sensitizers, XY1, XY2, and XY3, that exhibit high molar extinction
coefficients and a broad absorption range. Molecular modifications of these dyes,
featuring a benzothiadiazole (BTZ) auxiliary acceptor, were achieved by
introducing a thiophene heterocycle as well as by shifting the position of BTZ on
the conjugated bridge. The ensuing high molar absorption coefficients enabled the
fabrication of highly efficient thin-film solid-state DSSCs with only 1.3 MUm
mesoporous TiO2 layer. XY2 with a molar extinction coefficient of 6.66 * 10(4) M(
1) cm(-1) at 578 nm led to the best photovoltaic performance of 7.51%.
PMID- 27488267
TI - Bilateral Myeloid Sarcoma of Breast in a Young Male Occurring after 11 Years of
Chronic Myeloid Leukemia Diagnosis: A Unique Pattern of Relapse.
PMID- 27488266
TI - Indicated school-based intervention to improve depressive symptoms among at risk
Chilean adolescents: a randomized controlled trial.
AB - BACKGROUND: Depression is a disabling condition affecting people of all ages, but
generally starting during adolescence. Schools seem to be an excellent setting
where preventive interventions may be delivered. This study aimed to test the
effectiveness of an indicated school-based intervention to reduce depressive
symptoms among at-risk adolescents from low-income families. METHODS: A two-arm,
parallel, randomized controlled trial was conducted in 11 secondary schools in
vulnerable socioeconomic areas in Santiago, Chile. High-risk students in year 10
(2 degrees Medio) were invited to a baseline assessment (n = 1048). Those who
scored >=10 (boys) and >=15 (girls) in the BDI-II were invited to the trial (n =
376). A total of 342 students consented and were randomly allocated into an
intervention or a control arm in a ratio of 2:1. The intervention consisted of 8
group sessions of 45 min each, based on cognitive-behavioural models and
delivered by two trained psychologists in the schools. Primary (BDI-II) and
secondary outcomes (measures of anxiety, automatic thoughts and problem-solving
skills) were administered before and at 3 months post intervention. The primary
outcome was the recovery rate, defined as the proportion of participants who
scored in the BDI-II <10 (among boys) and <15 (among girls) at 3 months after
completing the intervention. RESULTS: There were 229 participants in the
intervention group and 113 in the control group. At 3-month follow-up 81.4 % in
the intervention and 81.7 % in the control group provided outcome data. The
recovery rate was 10 % higher in the intervention (50.3 %) than in the control
(40.2 %) group; with an adjusted OR = 1.62 (95 % CI: 0.95 to 2.77) (p = 0.08). No
difference between groups was found in any of the secondary outcomes. Secondary
analyses revealed an interaction between group and baseline BDI-II score.
CONCLUSIONS: We found no clear evidence of the effectiveness of a brief,
indicated school-based intervention based on cognitive-behavioural models on
reducing depressive symptoms among Chilean adolescents from low-income families.
More research is needed in order to find better solutions to prevent depression
among adolescents. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33871591 .
Retrospectively registered 29 June 2011.
PMID- 27488268
TI - One-Step Synthesis of Microporous Carbon Monoliths Derived from Biomass with High
Nitrogen Doping Content for Highly Selective CO2 Capture.
AB - The one-step synthesis method of nitrogen doped microporous carbon monoliths
derived from biomass with high-efficiency is developed using a novel ammonia
(NH3)-assisted activation process, where NH3 serves as both activating agent and
nitrogen source. Both pore forming and nitrogen doping simultaneously proceed
during the process, obviously superior to conventional chemical activation. The
as-prepared nitrogen-doped active carbons exhibit rich micropores with high
surface area and high nitrogen content. Synergetic effects of its high surface
area, microporous structure and high nitrogen content, especially rich nitrogen
containing groups for effective CO2 capture (i.e., phenyl amine and pyridine
nitrogen) lead to superior CO2/N2 selectivity up to 82, which is the highest
among known nanoporous carbons. In addition, the resulting nitrogen-doped active
carbons can be easily regenerated under mild conditions. Considering the
outstanding CO2 capture performance, low production cost, simple synthesis
procedure and easy scalability, the resulting nitrogen-doped microporous carbon
monoliths are promising candidates for selective capture of CO2 in industrial
applications.
PMID- 27488269
TI - The bile acid chenodeoxycholic acid directly modulates metabolic pathways in
white adipose tissue in vitro: insight into how bile acids decrease obesity.
AB - Obesity is a worldwide epidemic, and associated pathologies, including type 2
diabetes and cardiovascular alterations, are increasingly escalating morbidity
and mortality. Despite intensive study, no effective simple treatment for these
conditions exists. As such, the need for go-to drugs is serious. Bile acids (BAs)
present the possibility of reversing these problems, as various in vivo studies
and clinical trials have shown significant effects with regard to weight and
obesity reduction, insulin sensitivity restoration and cardiovascular
improvements. However, the mechanism of action of BA-induced metabolic
improvement has yet to be fully established. The currently most accepted model
involves non-shivering thermogenesis for energy waste, but this is disputed. As
such, we propose to determine whether the BA chenodeoxycholic acid (CDCA) can
exert anti-obesogenic effects in vitro, independent of thermogenic brown adipose
tissue activation. By exposing differentiated 3 T3-L1 adipocytes to high glucose
and CDCA, we demonstrate that this BA has anti-obesity effects in vitro. Nuclear
magnetic resonance spectroscopic analysis of metabolic pathways clearly indicates
an improvement in metabolic status, as these cells become more oxidative rather
than glycolytic, which may be associated with an increase in fatty acid
oxidation. Our work demonstrates that CDCA-induced metabolic alterations occur in
white and brown adipocytes and are not totally dependent on endocrine/nervous
system signaling, as thought until now. Furthermore, future exploration of the
mechanisms behind these effects will undoubtedly reveal interesting targets for
clinical modulation.
PMID- 27488270
TI - Proportional estimation of finger movements from high-density surface
electromyography.
AB - BACKGROUND: The importance to restore the hand function following an
injury/disease of the nervous system led to the development of novel
rehabilitation interventions. Surface electromyography can be used to create a
user-driven control of a rehabilitation robot, in which the subject needs to
engage actively, by using spared voluntary activation to trigger the assistance
of the robot. METHODS: The study investigated methods for the selective
estimation of individual finger movements from high-density surface
electromyographic signals (HD-sEMG) with minimal interference between movements
of other fingers. Regression was evaluated in online and offline control tests
with nine healthy subjects (per test) using a linear discriminant analysis
classifier (LDA), a common spatial patterns proportional estimator (CSP-PE), and
a thresholding (THR) algorithm. In all tests, the subjects performed an isometric
force tracking task guided by a moving visual marker indicating the contraction
type (flexion/extension), desired activation level and the finger that should be
moved. The outcome measures were mean square error (nMSE) between the reference
and generated trajectories normalized to the peak-to-peak value of the reference,
the classification accuracy (CA), the mean amplitude of the false activations
(MAFA) and, in the offline tests only, the Pearson correlation coefficient
(PCORR). RESULTS: The offline tests demonstrated that, for the reduced number of
electrodes (<=24), the CSP-PE outperformed the LDA with higher precision of
proportional estimation and less crosstalk between the movement classes (e.g., 8
electrodes, median MAFA ~ 0.6 vs. 1.1 %, median nMSE ~ 4.3 vs. 5.5 %). The LDA
and the CSP-PE performed similarly in the online tests (median nMSE < 3.6 %,
median MAFA < 0.7 %), but the CSP-PE provided a more stable performance across
the tested conditions (less improvement between different sessions). Furthermore,
THR, exploiting topographical information about the single finger activity from
HD-sEMG, provided in many cases a regression accuracy similar to that of the
pattern recognition techniques, but the performance was not consistent across
subjects and fingers. CONCLUSIONS: The CSP-PE is a method of choice for selective
individual finger control with the limited number of electrodes (<24), whereas
for the higher resolution of the recording, either method (CPS-PA or LDA) can be
used with a similar performance. Despite the abundance of detection points, the
simple THR showed to be significantly worse compared to both pattern
recognition/regression methods. Nevertheless, THR is a simple method to apply (no
training), and it could still give satisfactory performance in some subjects
and/or simpler scenarios (e.g., control of selected fingers). These conclusions
are important for guiding future developments towards the clinical application of
the methods for individual finger control in rehabilitation robotics.
PMID- 27488271
TI - Kinetic and computational analysis of the reversible inhibition of porcine
pancreatic elastase: a structural and mechanistic approach.
AB - Structural and mechanistic insights were revealed for the reversible inhibition
of Porcine Pancreatic Elastase (PPE); the kinetics of uninhibited and inhibited
hydrolysis of substrate Suc-AAA-pNA was analyzed thoroughly. Additionally, the
interactions between PPE and its inhibitor were studied by computational
techniques. The uninhibited hydrolysis of Suc-AAA-pNA by PPE proceeds through a
virtual transition state, involving an inferior physical and another dominating
chemical step, where two stabilized reactant states precede the predominant acyl
enzyme. Different kinds of bonding with the PPE-backbone residues, including
those of the catalytic triad, were found during the MD simulation of 5 ns, as key
interactions favoring a higher stabilization of the best ranked complex PPE
CF3C(O)-KA-NHPh-p-CF3. The proton inventories of the inhibited hydrolysis of Suc
AAA-pNA by PPE, were ruled out the existence of any virtual transition state and
thus they argue for a different mode of catalysis involving a structurally
disturbed PPE molecule. Thereafter, a novel inhibition mechanism was suggested.
PMID- 27488272
TI - A process evaluation of a cluster randomised trial to reduce potentially
inappropriate prescribing in older people in primary care (OPTI-SCRIPT study).
AB - BACKGROUND: The OPTI-SCRIPT cluster randomised controlled trial (RCT) found that
a three-phase multifaceted intervention including academic detailing with a
pharmacist, GP-led medicines reviews, supported by web-based pharmaceutical
treatment algorithms, and tailored patient information leaflets, was effective in
reducing potentially inappropriate prescribing (PIP) in Irish primary care. We
report a process evaluation exploring the implementation of the intervention, the
experiences of those participating in the study and lessons for future
implementation. METHODS: The OPTI-SCRIPT trial included 21 GP practices and 196
patients. The process evaluation used mixed methods. Quantitative data were
collected from all GP practices and semi-structured interviews were conducted
with GPs from intervention and control groups, and a purposive sample of patients
from the intervention group. All interviews were transcribed verbatim and
analysed using a thematic analysis. RESULTS: Despite receiving a standardised
academic detailing session, intervention delivery varied among GP practices. Just
over 70 % of practices completed medicines review as recommended with the patient
present. Only single-handed practices conducted reviews without patients present,
highlighting the influence of practice characteristics and resources on
variation. Medications were more likely to be completely stopped or switched to
another more appropriate medication when reviews were conducted with patients
present. The patient information leaflets were not used by any of the
intervention practices. Both GP (32 %) and patient (40 %) recruitment rates were
modest. For those who did participate, overall, the experience was positively
viewed, with GPs and patients referring to the value of medication reviews to
improve prescribing and reduce unnecessary medications. Lack of time in busy GP
practices and remuneration were identified as organisational barriers to future
implementation. CONCLUSIONS: The OPTI-SCRIPT intervention was positively viewed
by both GPs and patients, both of whom valued the study's objectives. Patient
information leaflets were not a successful component of the intervention.
Academic detailing and medication reviews are important components in changing
PIP, and having patients present during the review process seems to be a more
effective approach for decreasing PIP. TRIAL REGISTRATION: Current controlled
trials ISRCTN41694007 . Registered on 21 March 2012.
PMID- 27488274
TI - Prevention of microalbuminuria using early intervention with renin-angiotensin
system inhibitors in patients with type 2 diabetes: A systematic review.
AB - HYPOTHESIS/OBJECTIVES: Early prevention of diabetic nephropathy by way of
blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria
seems rational, but trials have so far shown conflicting results. The present
meta-analysis was undertaken to investigate if such treatment can prevent
development of microalbuminuria. MATERIALS AND METHODS: We searched MEDLINE,
EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials,
with a population of patients with type 2 diabetes and normoalbuminuria,
comparing angiotensin-converting enzyme inhibitors (ACEis) or angiotensin
receptor blockers (ARBs) to placebo. Studies had to have at least 50 participants
in each arm and one year of follow-up. Random and fixed effect models were
performed as well as trial sequential analysis. RESULTS: Six trials were included
in the analysis (n=16,921). Overall risk of bias was variable. In a fixed model
analysis ACE or ARB treatment was superior to placebo in relation to prevention
of development of microalbuminuria, risk ratio 0.84 (95% confidence interval (CI)
0.79-0.88) p<0.001, I(2)=23%, similar to random model results. Treatment also
showed a trend towards a reduction in all-cause mortality(p=0.07). CONCLUSIONS:
We conclude that in patients with type 2 diabetes and normoalbuminuria, early
intervention with ACEis or ARBs reduces the risk for development of
microalbuminuria.
PMID- 27488273
TI - Exposure to mercury in susceptible population groups living in the former mercury
mining town of Idrija, Slovenia.
AB - 500 years of mercury (Hg) mining in the town of Idrija has caused severe
pollution in Idrija and its surroundings. Following the closure of the mine in
1995, the environment remains contaminated with Hg. Sources of elemental-,
inorganic- and methyl Hg exposure were identified, potential environmental level
of exposure to Hg was evaluated and actual internal exposure to Hg was assessed
in selected susceptible population groups comprising school-age children and
pregnant women living in Idrija and in control groups from rural and urban
environments. The study of pregnant women (n=31) was conducted between 2003 and
2008, and the study of school-age children (n=176) in 2008. Potential interaction
of Hg with selenium (Se) in plasma was assessed in both study populations, while
in pregnant women antioxidative enzyme activity (glutathione peroxidase,
superoxide dismutase and catalase) in erythrocytes of maternal and cord blood was
also assessed. Actual exposure to Hg as indicated by levels of Hg in children's
blood (geometric mean (GM) 0.92ug/L), mother's blood (GM 1.86ug/L), children's
urine (GM 1.08ug/g crea.), mother's urine (GM 2.51ug/L), children's hair (GM
241ng/g) and mother's hair (GM 251ng/g) was higher in the two study groups from
Idrija than in the control groups from rural areas, but was still at the level of
a "normal" population and reflects mainly exposure to elemental Hg (Hg degrees )
from dental amalgam and, to a certain extent atmospheric Hg degrees .
Furthermore, the internal doses of Hg received during pregnancy did not decrease
the bioavailability of Se. Based on observation in children, the increase in Se
protein expression is suggested to be a consequence of moderately elevated
exposure to Hg degrees . The observed changes in activity of antioxidative
enzymes, as biomarkers of oxidative stress, appear to be mainly associated with
pregnancy per se and not with an increased exposure to Hg. In view of the
continuing increased potential for Hg exposure and the low number of pregnant
women studied, the results warrant a further longitudinal study of a larger group
of pregnant women residing in the area of the former mercury mine.
PMID- 27488275
TI - Angiotensin II Type 1 receptor (AGTR1) gene polymorphisms are associated with
vascular manifestations in patients with systemic sclerosis (SSc).
AB - INTRODUCTION: Systemic sclerosis (SSc) shows variable clinical expression in
different ethnic groups; vascular abnormalities are a prominent feature of this
disease and its clinical expression may be influenced by genetic factors.
PATIENTS AND METHODS: Herein, we describe 15 polymorphisms of the renin
angiotensin-aldosterone pathway in 170 Mexican admixed SSc patients (defined as
patients with Mexican ancestry for at least 3 generations) and 199 healthy
controls. We determined the presence of angiotensin II Type 1 receptor (AGTR1),
angiotensin converting enzyme (ACE) and Endothelin 1 single nucleotide
polymorphisms (SNPs) using 5' exonuclease TaqMan genotyping assays on a 7900HT
real-time fast polymerase chain reaction (PCR) system. RESULTS: These
polymorphisms had a similar distribution between SSc patients and controls, but
we found that the AGTR1 G-680T (rs275652) (p = 0.02; OR 3.5; 95%CI 1.2-10.4) and
AGTR1 A-119G (rs275653) (p = 0.008; OR 4.2; 95% CI 1.5-12.1) polymorphisms were
associated with severe vascular involvement in our SSc patients. CONCLUSIONS:
This is the first report of the association of these polymorphisms with
vasculopathy in Mexican admixed SSc patients. Our findings suggested that the
angiotensin II Type 1 receptor genotype may influence the clinical expression of
vasculopathy in these patients. Functional analyses should follow.
PMID- 27488276
TI - Serum activity of angiotensin converting enzyme 2 is decreased in patients with
acute ischemic stroke.
AB - Levels of angiotensin converting enzyme 2 (ACE2), a cardio and neuro-protective
carboxypeptidase, are dynamically altered after stroke in preclinical models. We
sought to characterize the previously unexplored changes in serum ACE2 activity
of stroke patients and the mechanism of these changes. Serum samples were
obtained from patients during acute ischemic stroke (n=39), conditions mimicking
stroke (stroke-alert, n=23), or from control participants (n=20). Enzyme activity
levels were analyzed by fluorometric assay and correlated with clinical variables
by regression analyses. Serum ACE2 activity was significantly lower in acute
ischemic stroke as compared to both control and stroke-alert patients, followed
by an increase to control levels at three days. Serum ACE2 activity significantly
correlated with the presence of ischemic stroke after controlling for other
factors (P=0.01). Additional associations with ACE2 activity included a positive
correlation with systolic blood pressure at presentation in stroke-alert
(R(2)=0.24, P=0.03), while stroke levels showed no correlation (R(2)=0.01,
P=0.50). ACE2 sheddase activity was unchanged between groups. These dynamic
changes in serum ACE2 activity in stroke, which concur with preclinical studies,
are not likely to be driven primarily by acute changes in blood pressure or
sheddase activity. These findings provide new insight for developing therapies
targeting this protective system in ischemic stroke.
PMID- 27488277
TI - Behavior of chemiluminescent assays to measure serum testosterone during androgen
deprivation therapy.
PMID- 27488278
TI - Weight loss among women and men in the ASPIRE-VA behavioral weight loss
intervention trial.
AB - OBJECTIVE: Weight loss was examined among women and men veterans in a clinical
trial comparing Aspiring for Lifelong Health (ASPIRE), a "small changes" weight
loss program using either mixed-sex group-visit or telephone-based coaching, to
MOVE!((r)) , the usual mixed-sex group-based program. METHODS: Linear mixed
effects models were used to calculate adjusted percent weight change at 12 months
by sex and compare outcomes across arms within sex. RESULTS: Analyses included 72
women (ASPIRE-Phone = 26; ASPIRE-Group = 26; MOVE! = 20) and 409 men (ASPIRE
Phone = 136; ASPIRE-Group = 134; MOVE! = 139). At 12 months, women displayed
significant weight loss from baseline in ASPIRE-Group (-2.6%) and MOVE! (-2.7%),
but not ASPIRE-Phone (+0.2%). Between-arm differences in weight change among
women were: ASPIRE-Group versus ASPIRE-Phone, -2.8% (P = 0.15); MOVE! versus
ASPIRE-Phone, -2.8% (P = 0.20); and ASPIRE-Group versus MOVE!, 0.0% (P = 1.0). At
12 months, men lost significant weight from baseline across arms (ASPIRE-Phone,
1.5%; ASPIRE-Group, -2.5%; MOVE!, -1.0%). Between-arm differences in weight
change among men were: ASPIRE-Group versus ASPIRE-Phone, -0.9% (P = 0.23); MOVE!
versus ASPIRE-Phone, +0.5% (P = 0.76); ASPIRE-Group versus MOVE!, -1.5% (P =
0.03). CONCLUSIONS: Mixed-sex, group-based programs can result in weight loss for
both women and men veterans.
PMID- 27488280
TI - Oxytetracycline recovery from aqueous media using computationally designed
molecularly imprinted polymers.
AB - Polymers for recovery/removal of the antimicrobial agent oxytetracycline (OTC)
from aqueous media were developed with use of computational design and molecular
imprinting. 2-Hydroxyethyl methacrylate, 2-acrylamide-2-methylpropane sulfonic
acid (AMPS), and mixtures of the two were chosen according to their predicted
affinity for OTC and evaluated as functional monomers in molecularly imprinted
polymers and nonimprinted polymers. Two levels of AMPS were tested. After bulk
polymerization, the polymers were crushed into particles (200-1000 MUm).
Pressurized liquid extraction was implemented for template removal with a low
amount of methanol (less than 20 mL in each extraction) and a few extractions (12
18 for each polymer) in a short period (20 min per extraction). Particle size
distribution, microporous structure, and capacity to rebind OTC from aqueous
media were evaluated. Adsorption isotherms obtained from OTC solutions (30-110 mg
L(-1)) revealed that the polymers prepared with AMPS had the highest affinity for
OTC. The uptake capacity depended on the ionic strength as follows: purified
water > saline solution (0.9 % NaCl) > seawater (3.5 % NaCl). Polymer particles
containing AMPS as a functional monomer showed a remarkable ability to clean
water contaminated with OTC. The usefulness of the stationary phase developed for
molecularly imprinted solid-phase extraction was also demonstrated. Graphical
Abstract Selection of functional monomers by molecular modeling renders polymer
networks suitable for removal of pollutants from contaminated aqueous
environments, under either dynamic or static conditions.
PMID- 27488282
TI - New Stethoscope With Extensible Diaphragm.
AB - BACKGROUND: This study compared the diagnostic efficacy of the common suspended
diaphragm stethoscope (SDS) with a new extensible diaphragm stethoscope (EDS) for
low-frequency heart sounds. METHODS AND RESULTS: The EDS was developed by using
an ethylene propylene diene monomer diaphragm. The results showed that the EDS
enhanced both the volume and quality of low-frequency heart sounds, and improved
the ability of examiners to auscultate such heart sounds. CONCLUSIONS: Based on
the results of the sound analysis, the EDS is more efficient than the SDS. (Circ
J 2016; 80: 2047-2049).
PMID- 27488281
TI - Redefining the role of peripheral LPS as a neuroinflammatory agent and evaluating
the role of hydrogen sulphide through metformin intervention.
AB - OBJECTIVE: The present study was aimed to enumerate the role of metformin
associated H2S release against lipopolysaccharide (LPS) induced
neuroinflammation. MATERIALS AND METHODS: Five groups of animals were subjected
to treatment as control (normal saline), toxic control (LPS, 125 ug/kg, i.p.),
and three separate groups treated with 6.25, 12.5, and 25 mg/kg of metformin
along with LPS for a period of 28 days. LPS was administered on 1st, 2nd, 3rd,
4th, 23rd, 24th, 25th and 26th day. The animals were evaluated for behavioral
(elevated plus maze, rotarod and actophotometer); biochemical (plasma and tissue
H2S, COX, LOX and NO), antioxidant (TBARS, SOD, catalase, protein carbonyl and
GSH) and liver toxicity (SGOT and SGPT) markers. The brain tissues were further
evaluated histopathologically, free fatty acid profile and NF-kappaB expression.
RESULT: The LPS could not hasten any significant behavioral, biochemical,
antioxidant and histopathological changes in the brain tissue. LPS also failed to
modify the free fatty acid profile and NF-kappaB expression in the brain tissue.
The LPS demarcated a well-defined peripheral inflammation as perceived through
the plasma H2S, NO, SGOT and SGPT. Metformin administration demonstrated a marked
effect on the peripheral inflammation induced by LPS. CONCLUSION: The LPS (i.p.)
administration is devoid of any neuroinflammatory effects; however, precipitates
peripheral inflammatory reactions and the same can could be attributed to the
fact that LPS is devoid of/confined by very minimal permeability across the blood
brain barrier. Metformin demonstrated a significant effect on peripheral
inflammatory reactions precipitated through LPS.
PMID- 27488283
TI - Right Heart Hemodynamics in Pulmonary Hypertension - An Echocardiography and
Catheterization Study.
AB - BACKGROUND: Echocardiography (ECHO) plays a key role in both the diagnosis and
prognosis of pulmonary hypertension (PH). Many equations have been published to
assess right heart hemodynamics using ECHO. The objective of this study was to
test the accuracy and precision of different echocardiographic equations in
comparison with the right heart catheterization. METHODS AND RESULTS: Complete
right heart hemodynamic assessments were prospectively obtained from 115
individuals (mean age 66+/-1 years; 57 males) who had known or suspected PH.
Several equations were tested for the estimation of right atrial pressure, mean
and systolic pulmonary artery pressure (MPAP), cardiac output, pulmonary
capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). The
accuracy of ECHO was good, with a mean difference <2 mmHg for all of the pressure
calculations and +/-0.6 L/min for cardiac output. However, the PVR estimation was
weak using any one of the formulae. For all the parameters, the precision of ECHO
was moderate. The MPAP calculation detected PH with a sensibility of 97% and
specificity of 83%. However, ECHO underdiagnosed post-capillary PH. CONCLUSIONS:
ECHO is a good method for the diagnosis of PH, with an adequate calculation of
right pressures, but cannot accurately calculate PCWP and PVR. (Circ J 2016; 80:
2019-2025).
PMID- 27488284
TI - Angioscopic Assessment of Stent Stability and Neointimal Coverage After
Implantation of 2nd-Generation Drug-Eluting Stents - Comparison With Bare-Mental
Stents and 1st-Generation Drug-Eluting Stents.
PMID- 27488285
TI - Dawn of a New Era - The Far Lower, the Far Better Low-Density Lipoprotein
Cholesterol Story in Japan.
PMID- 27488286
TI - Old landfill leachate treatment through multistage process: membrane adsorption
bioreactor and nanofitration.
AB - A bench-scale integrated process based on submerged aerobic powdered activated
carbon-membrane bioreactor (PAC-MBR) has been utilized and established for the
treatment of landfill leachate. The results showed that the submerged PAC-MBR
system effectively removed biodegradable trace organic compounds by the average
removal rate about 71 % at optimum food to microorganism (F/M) ratio of 0.4
gCOD/g day under a HRT of 24 h. Adding nanofiltration (NF) process increased the
treatment efficiency up to 99 %. Further, adding powdered activated carbon to
activated sludge (AS) resulted in a higher adsorption capacity in comparison with
AS. Adsorption isotherms were investigated and fitted by the Langmuir and
Freundlich isotherm models in which the Langmuir model performed better. The
specific oxygen uptake rate (SOUR) showed that adding PAC reduces the effects of
COD on microorganism activities. NH3-N, TKN and Heavy metals removal efficiency
amounted to 97 +/- 2, 96 +/- 2, and 99 +/- 2 %, respectively.
PMID- 27488287
TI - Functional acute liver failure after treatment with pegylated asparaginase in a
patient with acute lymphoblastic leukemia: potential impact of plasmapheresis.
PMID- 27488288
TI - Synthesis of esters via sp(3) C-H functionalisation.
AB - Oxidative C-O bond formation via sp(3) C-H functionalisation represents an
attractive approach for the synthesis of esters. This review focuses on the
recent advances of sp(3) C-H bond functionalisation strategies for ester
synthesis from unconventional precursors using transition metal/metal free
catalysts in combination with various oxidants. Various classes of esters and the
mechanisms of their formation are discussed with numerous examples.
PMID- 27488289
TI - Clinical and Radiological Study Focused on Relief of Low Back Pain After
Decompression Surgery in Selected Patients With Lumbar Spinal Stenosis Associated
With Grade I Degenerative Spondylolisthesis.
AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of the present study was
to identify the clinical and radiological features of low back pain (LBP) that
was relieved after decompression alone of lumbar spinal stenosis (LSS) associated
with grade I lumbar degenerative spondylolisthesis (LDS). SUMMARY OF BACKGROUND
DATA: Although decompression and fusion are generally the recommended surgical
treatments of LDS, several authors have reported that some patients with LDS
could obtain good clinical results including relief from LBP by decompression
alone. The pathogenesis of relief from LBP after decompression is, however, not
known. METHODS: Forty patients with LSS associated with grade I LDS, who
underwent a minimally invasive surgical-decompression were enrolled in the
present study. All patients complained preoperatively of predominantly leg
related symptoms and LBP (>= 4 points on Numeric Rating Scale). Clinical and
radiological assessments were performed 1 year after surgery (a relief of LBP:
Numeric Rating Scale reduction >=3 points and valuation <=3 points) and at the
last follow-up. We conducted a comparative study between patient groups with and
without the relief from LBP (groups R and N, respectively). RESULTS: Twenty-nine
patients were distributed to group R and the remaining 11 patients to group N.
Preoperatively, there was a significant difference between the two groups for age
and radiographic flexibility for lumbar extension. Postoperatively, there was a
positive correlation between improvement in both LBP and leg symptoms. The
clinical outcomes of group R were significantly better than those of group N
throughout follow-up period (mean 37 mo). In group R, sagittal lumbopelvic
radiographic parameters improved significantly after surgery. CONCLUSION:
Although the causes of LBP are varied in each patients, our results show that
concomitant LSS itself might cause LBP in some patients with grade I LDS, because
it involves impingement of the neural tissue and discordant sagittal lumbopelvic
alignment. LEVEL OF EVIDENCE: 3.
PMID- 27488290
TI - Direct Repair of Lumbar Pars Interarticularis Defects by Utilizing Intraoperative
O-Arm-Based Navigation and Microendoscopic Techniques.
AB - STUDY DESIGN: A retrospective analysis of the clinical outcomes of eight patients
with the lumbar pars interarticulars defects treated by direct repair with the
aid of intraoperative O-arm based navigation and microendoscopic techniques.
OBJECTIVE: The aim of this study was to investigate the efficacy and safety of
direct screw repair by using minimally invasive surgery for the lumbar pars
interarticulars defects in a pilot study. SUMMARY OF BACKGROUND DATA: Direct
repair of pars interarticulars defects has been used to treat young adult
patients. Reports concerning direct repair by minimally invasive techniques for
pars interarticulars defects are quite rare. METHODS: Review of medical records
identified eight consecutive patients treated with intraoperative O-arm based
navigation and microendoscopic techniques. Debridement and autograft of pars
interarticularis defects was performed under microendoscopic procedure. Then,
percutaneous bilateral intralaminar screws were inserted by utilizing
intraoperative navigation. The clinical and radiological data were collected and
analyzed retrospectively. RESULTS: Eight patients had a mean age of 28.4 years,
and five were 30 years or younger at the time of treatment. Symptoms included
axial back pain in 100% of patients without concomitant radiculopathy. Autograft
was used in all cases. The average follow-up duration was 27.4 months with a
range of 20 to 33 months. Symptoms resolved completely or partially in all
patients. Low back pain visual analog scores decrease from preoperative 6.8 to
postoperative 1.4 of eight cases. Of 16 pars defects, healing was observed in 13
(81.3%) at last radiological follow-up. One patient with bilateral fusion failure
refused revision surgery because of mild complaint. No complications such as
dural tear, nerve root injury, and infection occurred. CONCLUSION: Minimally
invasive direct repair of the pars interarticularis defects with intralaminar
screws by using microendoscopic system and navigation procedure can provide safe
and effective treatment of spondylolysis with satisfactory clinical and
radiological outcomes, which need some special tools with steep learning curve.
LEVEL OF EVIDENCE: 4.
PMID- 27488291
TI - Increased Segmental Range of Motion Is Correlated With Spondylolisthesis in the
Cervical Spine After Laminoplasty.
AB - STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to
determine the incidence of increased segmental range of motion (ROM) after
laminoplasty and to clarify whether increased ROM is associated with
spondylolisthesis. Finally, we explored the effect of increased segmental ROM on
clinical results. SUMMARY OF BACKGROUND DATA: Cervical laminoplasty for cervical
spondylotic myelopathy causes reduced ROM, possibly due to the unintended
contracture of the facet joint or a bony union. Although it is rarely studied,
ROM may also increase following laminoplasty. Thus far, there are no reports
describing the correlation between increased segmental ROM and segmental
spondylolisthesis after laminoplasty. METHODS: We evaluated 187 segments from 39
cervical spondylotic myelopathy patients who underwent bilateral open door
laminoplasty from C2 to C7. The segmental ROM and spondylolisthesis were measured
using dynamic radiographs that were obtained preoperatively and 2 years
postoperatively. The Japanese Orthopedic Association (JOA) score was used for
clinical evaluation. To compare the clinical results, we compared the cases with
increased ROM in at least one segment with the remaining cases. RESULTS:
Increased segmental ROM (i.e., >=5 degrees increase) was observed in 25 of 187
segments (13.4%) from 14 cases. There was a strong correlation between increased
ROM and spondylolisthesis. A high preoperative disc height was associated with
increased segmental ROM 2 years postoperation. Regardless of the correlation with
spondylolisthesis, there was no statistically significant correlation between
increased segmental ROM and JOA score. CONCLUSION: The decrease in segmental ROM
after laminoplasty was not uniform. Approximately 13.4% of all segments showed
increased ROM. The preoperative disc height might influence the risk for
increased segmental ROM. Furthermore, increased ROM was correlated with
spondylolisthesis in the segment, though it was not correlated with clinical
results. LEVEL OF EVIDENCE: 4.
PMID- 27488292
TI - Impact of Insulin Dependence on Perioperative Outcomes Following Anterior
Cervical Discectomy and Fusion.
AB - STUDY DESIGN: A retrospective analysis of prospectively collected data.
OBJECTIVE: Our objective was to analyze insulin-dependent and noninsulin
dependent diabetes mellitus (IDDM and NIDDM) as potential risk factors for
complications, reoperations, and readmissions within 30 days following anterior
cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is a
common surgical procedure with growing utilization and good long-term outcomes.
Readmissions and reoperations are associated with increased morbidity and
inferior long-term outcomes. IDDM and NIDDM are often associated with increased
complication rates. METHODS: This was a retrospective analysis of prospectively
collected data from the ACS NSQIP database. Patients >=18 years old undergoing
ACDF from 2005 to 2012 were included. Readmission, perioperative events, and
reoperation within 30 days following ACDF were measured. Patient demographics,
perioperative data, preoperative labs, and postoperative events were assessed.
Patients with NIDDM or IDDM were compared with nondiabetic patients using
multivariate logistic regression analysis with significance defined as P < 0.05.
Odds ratio (OR) was calculated with a 95% confidence interval (CI). RESULTS:
Three thousand seven hundred twenty-six patients were included of whom 270 were
NIDDM and 171 IDDM. Readmissions and reoperation data were available only from
2011 to 2012, including 1423 nondiabetes mellitus (non-DM), 193 NIDDM, and 87
IDDM cases. NIDDM was associated with higher rates of urinary tract infection
(UTI) (P < 0.007), and return to operating room (P = 0.012) than nondiabetic
patients. IDDM was associated with higher rates of reoperations (P = 0.04),
readmissions (P < 0.0001), and total length of stay (LOS) >5 days (P < 0.0001).
Following adjusted multivariate analysis, only IDDM status remained an
independent predictor for 30-day readmission (OR 4.8, 95% CI 2.3-10.1).
CONCLUSION: Patients with NIDDM and IDDM were at an increased risk for several
postoperative complications following ACDF. IDDM was independently associated
with increased 30-day readmission rates. Diabetic patients should be counseled
appropriately, and the importance of close perioperative care is highlighted in
this study. LEVEL OF EVIDENCE: 3.
PMID- 27488293
TI - Evidence-Based Review and Survey of Expert Opinion of Reconstruction of
Metastatic Spine Tumors.
AB - STUDY DESIGN: Systematic review and consensus expert opinion. OBJECTIVE: To
provide surgeons and other health care professionals with guidelines for surgical
reconstruction of metastatic spine disease based on evidence and expert opinion.
SUMMARY OF BACKGROUND DATA: The surgical treatment of spinal metastases is
controversial. Specifically two aspects of surgical reconstruction are addressed
in this study: (i) choice of bone graft used during surgery for metastatic spine
tumors and (ii) the design of reconstruction or construct to stabilize. METHODS:
A systematic review of the available medical literature from 1980 to 2015 was
conducted, and combined with consensus expert opinion from a recent survey of
spine surgeons who treat metastatic spine tumors. RESULTS: There is very little
evidence in the literature to provide guidance on the use of bone graft in
metastatic tumor reconstruction. There is little evidence in the literature to
support the preferential use of one graft type over the other. Approximately, 41%
of respondents said they used bone graft or bone graft substitutes to accomplish
fusion. There were 17 studies that described the use of a prefabricated
prosthetic, 10 studies describing the use of polymethyl methacrylate (PMMA) bone
cement, and only three studies describing the use of bone graft for anterior
column reconstruction. The use of structural allograft was most popular among the
experts for anterior reconstruction, followed by cage reconstruction, and PMMA
bone cement. CONCLUSION: Achieving bony union may be of importance for the
maintenance of spinal stability in the long term after reconstruction. Whether
bony union is required for patients with shorter life expectancies is debatable.
The literature supports the use of anterior reconstruction with either a
prefabricated prosthetic or PMMA bone cement. It also supports the use of an
anterior construct reinforced with bilateral posterior instrumentation when
performing a three-column reconstruction. LEVEL OF EVIDENCE: N/A.
PMID- 27488294
TI - Stereotactic Body Radiotherapy for Spinal Metastases: What are the Risks and How
Do We Minimize Them?
AB - STUDY DESIGN: Systematic literature review. OBJECTIVES: To summarize the risks of
3 key complications of stereotactic body radiotherapy (SBRT) for spinal
metastases, that is, radiation myelopathy (RM), vertebral compression fracture
(VCF), and epidural disease progression, and to discuss strategies for minimizing
them. SUMMARY OF BACKGROUND DATA: RM, VCF and epidural disease progression are
now recognized as important risks following SBRT for spine metastases. It is
unclear at this stage exactly how large these risks are and what strategies can
be employed to minimize these risks. METHODS: A systematic review of the
literature using MEDLINE and a review of the bibliographies of reviewed articles
on SBRT for spinal metastases were conducted. RESULTS: The initial literature
search revealed a total of 376 articles, of which 38 were pertinent to the study
objectives. The risk of RM following SBRT was found to be dependent on the
maximum dose to the spinal cord and estimated to be <=5% if the recommended
published thecal sac dose constraints are adhered to. The crude risk of VCF was
13.7% (range: 0.7%-40.5%), and, on average, 45% were surgically salvaged. It has
been shown that the risk of VCF is dependent on several anatomic and tumor
related factors including the SBRT dose per fraction. The crude risk of local
failure at 1 year was 21.4% (range: 12%-27%) of which 67% (range: 38%-96%)
occurred within the epidural space. The grade of epidural disease has been shown
to be associated with the risk of local failure. CONCLUSION: The risk of RM after
spinal SBRT is low in particular if recommended dose metrics are adhered to.
There is a significant risk of both VCF and epidural disease progression after
spinal SBRT. These risks can potentially be minimized by identifying the risk
factors for these complications, and performing careful radiotherapy and surgical
planning. LEVEL OF EVIDENCE: 2.
PMID- 27488295
TI - Benign Tumors of the Spine: Has New Chemotherapy and Interventional Radiology
Changed the Treatment Paradigm?
AB - STUDY DESIGN: Clinically based systematic review. OBJECTIVE: To determine the
role of (A) medical treatment and (B) interventional radiology as either adjuvant
or stand-alone treatment in primary benign bone tumors of the spine. METHODS: A
multidisciplinary panel of spine surgeons, radiation oncologists, and medical
oncologists elaborated specific focused questions regarding aneurysmal bone cyst,
giant cell tumor, and osteoid osteoma. Denosumab, bisphosphonate, interferon,
bone marrow aspirate, doxycycline, thermal ablation, and selective arterial
embolization were identified as areas of interest for the article. A systematic
review was performed through MEDLINE and EMBASE. Recommendations based on the
literature review and clinical expertise were issued using the GRADE system.
RESULTS: The overall quality of the literature is very low with few multicenter
prospective studies. For giant cell tumor, combination with Denosumab identified
14 pertinent articles with four multicenter prospective studies. Nine studies
were found on bisphosphonates and six for selective arterial embolization. The
search on aneurysmal bone cyst and selective arterial embolization revealed 12
articles. Combination with Denosumab, Doxycycline, and bone marrow aspirate
identified four, two, and three relevant articles respectively. Eleven focused
articles were selected on the role of thermal ablation in osteoid osteoma.
CONCLUSION: Alternative and adjuvant therapy for primary benign bone tumors have
emerged. Their ability to complement or replace surgery is now being scrutinized
and they may impact significantly the algorithm of treatment of these tumors.
Most of the data are still emerging and further research is desirable. Close
collaboration between the different specialists managing these pathologies is
crucial. LEVEL OF EVIDENCE: N/A.
PMID- 27488296
TI - A Systematic Review With Consensus Expert Opinion of Best Reconstructive
Techniques After Osseous En Bloc Spinal Column Tumor Resection.
AB - STUDY DESIGN: Systematic literature review and consensus expert opinion.
OBJECTIVE: To provide recommendations on reconstructive constructs for large
tumor resections of the spinal column. Four questions were studied: (1) What are
the best reconstructive options for single versus multilevel resections? (2)
Should short segment fixation be considered in primary tumor reconstruction? (3)
How should reconstructive techniques differ at various regions of the spine? (4)
Does planned postoperative radiation change the fusion strategy? SUMMARY OF
BACKGROUND DATA: Primary spinal tumors requiring en bloc resection are rare. Most
studies focus on disease-free survival and local recurrence rates. Few studies
focus on reconstructive options and outcomes with respect to fusion rates and
need for revision. METHODS: A literature search was performed from January 1990
to December 2013. Data were combined and construct survivorship summarized. A
survey was administered to international spine tumor surgeons, evaluating
reconstructive preferences. RESULTS: The search yielded 381 articles, 12 included
in the final analysis. Revision rates for anterior reconstruction were similar
for autogenous strut grafts (10%), cages (7.7%), and allograft strut grafts
(8.3%). There were two reports of revision from short to long segment constructs
and three reports of broken pedicle screws, one requiring revision. Expert survey
results revealed that most surgeons preferred cages packed with morcelized
allograft and autograft (75%) for anterior reconstruction of single-level
vertebrectomies, and strut bone grafting at the cervicothoracic junction (65%)
and when more than one vertebrae was resected in the mid-thoracic spine (75%).
Surgeons may alter their fusion technique if postoperative radiation is planned.
CONCLUSION: Posterior reconstruction with at least two vertebral levels above and
below is recommended. Cages should be used for single-level defects and
structural bone graft alone, or in combination with a cage, should be used when
spanning a defect greater than two vertebral bodies. Planned postoperative
radiation may affect fusion strategy. LEVEL OF EVIDENCE: N/A.
PMID- 27488297
TI - The Spinal Instability Neoplastic Score: Impact on Oncologic Decision-Making.
AB - STUDY DESIGN: Systematic literature review. OBJECTIVE: To address the following
questions in a systematic literature review: 1. How is spinal neoplastic
instability defined or classified in the literature before and after the
introduction of the Spinal Instability Neoplastic Score (SINS)? 2. How has SINS
affected daily clinical practice? 3. Can SINS be used as a prognostic tool?
SUMMARY OF BACKGROUND DATA: Spinal neoplastic-related instability was defined in
2010 and simultaneously SINS was introduced as a novel tool with criteria agreed
upon by expert consensus to assess the degree of spinal stability. METHODS:
PubMed, Embase, and clinical trial databases were searched with the key words
"spinal neoplasm," "spinal instability," "spinal instability neoplastic score,"
and synonyms. Studies describing spinal neoplastic-related instability were
eligible for inclusion. Primary outcomes included studies describing and/or
defining neoplastic-related instability, SINS, and studies using SINS as a
prognostic factor. RESULTS: The search identified 1414 articles, of which 51 met
the inclusion criteria. No precise definition or validated assessment tool was
used specific to spinal neoplastic-related instability prior to the introduction
of SINS. Since the publication of SINS in 2010, the vast majority of the
literature regarding spinal instability has used SINS to assess or describe
instability. Twelve studies specifically investigated the prognostic value of
SINS in patients who underwent radiotherapy or surgery. CONCLUSION: No consensus
could be determined regarding the definition, assessment, or reporting of
neoplastic-related instability before introduction of SINS. Defining spinal
neoplastic-related instability and the introduction of SINS have led to improved
uniform reporting within the spinal neoplastic literature. Currently, the
prognostic value of SINS is controversial. LEVEL OF EVIDENCE: N/A.
PMID- 27488298
TI - Clinical Decision Making: Integrating Advances in the Molecular Understanding of
Spine Tumors.
AB - STUDY DESIGN: Literature review. OBJECTIVE: To describe advancements in molecular
techniques, biomarkers, technology, and targeted therapeutics and the potential
these modalities hold to predict treatment paradigms, clinical outcomes, and/or
survival in patients diagnosed with primary spinal column tumors. SUMMARY OF
BACKGROUND DATA: Advances in molecular technologies and techniques have
influenced the prevention, diagnosis, and overall management of patients
diagnosed with cancer. Assessment of genomic, proteomic alterations, epigenetic,
and posttranslational modifications as well as developments in diagnostic
modalities and targeted therapeutics, although the best studied in nonspinal
metastatic disease, have led to increased understanding of spine oncology that is
expected to improve patient outcomes. In this manuscript, the technological
advancements that are expected to change the landscape of spinal oncology are
discussed with a focus on how these technologies will aid in clinical decision
making for patients diagnosed with primary spinal tumors. METHODS: A review of
the literature was performed focusing on studies that integrated next-generation
sequencing, circulating tumor cells/circulating tumor DNA, advances in imaging
modalities and/or radiotherapy in the diagnosis and treatment of cancer. RESULTS:
We discuss genetic and epigenetic drivers, aberrations in receptor tyrosine
kinase signaling, and emerging therapeutic strategies that include receptor
tyrosine kinase inhibitors, immunotherapy strategies, and vaccine-based cancer
prevention strategies. CONCLUSION: The wide range of approaches currently in use
and the emerging technologies yet to be fully realized will allow for better
development of rationale therapeutics to improve patient outcomes. LEVEL OF
EVIDENCE: N/A.
PMID- 27488299
TI - Molecular Markers and Targeted Therapeutics in Metastatic Tumors of the Spine:
Changing the Treatment Paradigms.
AB - STUDY TYPE: A review of the literature. OBJECTIVE: The aim of this study was to
discuss the evolution of molecular signatures and the history and development of
targeted therapeutics in metastatic tumor types affecting the spinal column.
SUMMARY OF BACKGROUND DATA: Molecular characterization of metastatic spine tumors
is expected to usher in a revolution in diagnostic and treatment paradigms.
Molecular characterization will provide critical information that can be used for
initial diagnosis, prognosticating the ideal treatment strategy, assessment of
treatment efficacy, surveillance and monitoring recurrence, and predicting
complications, clinical outcome, and overall survival in patients diagnosed with
metastatic cancers to the spinal column. METHODS: A review of the literature was
performed focusing on illustrative examples of the role that molecular-based
therapeutics have played in clinical outcomes for patients diagnosed with
metastatic tumor types affecting the spinal column. RESULTS: The impact of
molecular therapeutics including receptor tyrosine kinases and immune checkpoint
inhibitors and the ability of molecular signatures to provide prognostic
information are discussed in metastatic breast cancer, lung cancer, prostate
cancer, melanoma, and renal cell cancer affecting the spinal column. CONCLUSION:
For the providers who will ultimately counsel patients diagnosed with metastases
to the spinal column, molecular advancements will radically alter the
management/surgical paradigms utilized. Ultimately, the translation of these
molecular advancements into routine clinical care will greatly improve the
quality and quantity of life for patients diagnosed with spinal malignancies and
provide better overall outcomes and counseling for treating physicians. LEVEL OF
EVIDENCE: N/A.
PMID- 27488300
TI - Predicting Neurologic Recovery after Surgery in Patients with Deficits Secondary
to MESCC: Systematic Review.
AB - STUDY DESIGN: Systematic literature review and expert survey OBJECTIVE.: The aim
of this study was to determine factors associated with neurologic improvement in
patients with neurologic deficits secondary to metastatic epidural spinal cord
compression (MESCC). Clear understanding of these factors will guide surgical
decision-making by helping to elucidate which patients are more likely to benefit
from surgery and how surgeons can increase the probability of neurologic and
functional restoration. SUMMARY OF BACKGROUND DATA: Surgical spinal cord
decompression has been shown to improve neurologic function in patients with
symptomatic MESCC. However, prognostication of neurologic improvement after
surgery remains challenging, owing to sparse data and complexity of these
patients. METHODS: PubMed and Embase databases were searched for relevant
publications. PRISMA Statement guided publication selection and data reporting.
GRADE guidelines were used for evidence quality evaluation and recommendation
formulation. RESULTS: Low-quality evidence supports the use of the duration and
severity of neurologic deficit as predictors of neurological recovery in patients
with MESCC. Low-quality evidence supports the use of thoracic level of
compression and previous irradiation as adverse predictors of neurological
recovery. Nearly all of the AOSpine Knowledge Forum Tumor members who responded
to the survey agreed that ambulation with assistance represented a successful
surgical result and that duration of ambulation loss and the severity of weakness
should be considered when trying to predict whether surgery would result in
restoration of ambulation. CONCLUSIONS: Review of literature and expert opinion
support the importance of duration of ambulation loss and the severity of
neurologic deficit (muscle strength, bladder function) in prediction of
neurologic recovery among patients with symptomatic MESCC. Efforts to reduce the
duration of ambulation loss and to prevent progression of neurologic deficits
should be made to improve the probability of neurologic recovery. LEVEL OF
EVIDENCE: 2.
PMID- 27488301
TI - Impact of Age on 30-day Complications After Adult Deformity Surgery.
AB - STUDY DESIGN: A retrospective analysis. OBJECTIVE: The aim of this study was to
identify whether age is a risk factor for postoperative complications after adult
deformity surgery (ADS). SUMMARY OF BACKGROUND DATA: Spinal deformity is a
prevalent cause of morbidity in the elderly population, occurring in as many as
68% of patients older than 60 years. Given the increasing prevalence of adult
spinal deformities and an aging population, understanding the safety of ADS in
elderly patients is becoming increasingly important. METHODS: A retrospective
cohort analysis was performed on the American College of Surgeons National
Surgical Quality Improvement Program (ACS NSQIP) database from 2010 to 2014.
Patients (>=18 years of age) from the NSQIP database undergoing ADS were
separated into age-based cohorts (<=52, 53-61, 62-69, and >=70 years of age). Age
groups were determined by interquartile analysis. Chi-squared, t tests, and
multivariate logistic regression models were used to identify independent risk
factors. RESULTS: A total of 5805 patients met the inclusion criteria. Age groups
1, 2, 3, and 4 contained 1518 (26.1%), 1478 (25.4%), 1451 (25.0%), and 1358
(23.4%) patients, respectively. Multivariate logistic regression analysis
revealed increasing age (relative to age group 1) to be an independent risk
factor for prolonged length of stay [odds ratio (OR) 1.39, confidence interval
(CI) 1.12-1.69], all complications (OR 1.64, CI 1.35-2.00), renal complications
(OR 3.45, CI 1.43-8.33), urinary tract infection (OR 2.70, CI 1.49-4.76),
postoperative transfusion (OR 1.47, CI 1.20-1.82), and unplanned readmission (OR
1.64, CI 1.18-2.23). Gradations in ORs existed between the different cohorts,
such that the deleterious effect of age was less pronounced in cohort 3 compared
with cohort 4, and even more less so between cohort 2 and cohort 4. CONCLUSION:
Age has been shown to be an independent risk factor for increased length of stay,
all complications, renal complications, urinary tract infection, transfusion, and
unplanned readmission. LEVEL OF EVIDENCE: 3.
PMID- 27488302
TI - Risk factors in multiple sclerosis: a population-based case-control study in
Sicily. Background and methods.
AB - Incidence of multiple sclerosis (MS) has steeply increased over time during the
last 30 years in the city of Catania. We carried out a population-based case
control study to evaluate the possible role of both environmental and genetic
factors. From 1975 to 2004 in Catania, 367 MS patients diagnosed according to the
Poser's criteria had the onset of disease. A sample of MS patients was randomly
selected from this incident cohort. Three controls matched by age and sex were
randomly selected from the rosters of 14 GPs. Controls were proportionally
selected according to the distribution by municipality of the target population
using a multistage sampling methods. All cases and controls underwent a face-to
face interview to record information concerning environmental factors and a blood
sample was taken for serological and genetic analysis. 164 MS patients (64 %
women; mean age of 46.4 +/- 10.7) and 481 controls (69 % women; mean age of 47.7
+/- 14.8) were enrolled in the study. The distribution of the whole population
and the selected controls by municipalities was similar. A blood sample was taken
from 150 MS cases and from 337 controls. At the end of the enrolment, we obtained
a representative sample of the MS cases and population controls avoiding possible
selection bias. Participation rate was very high also concerning the collection
of biological specimens.
PMID- 27488303
TI - Asymptomatic central pontine myelinolysis without hyponatriemia in diffuse large
B cell lymphoma.
PMID- 27488304
TI - Inhibition of P-TEFb disrupts global transcription, oocyte maturation, and embryo
development in the mouse.
AB - Positive transcription elongation factor b (P-TEFb) is an RNA polymerase II
kinase that phosphorylates Ser2 of the carboxyl-terminal domain and promotes the
elongation phase of transcription. Despite the fact that P-TEFb has role in many
cellular processes, the role of this kinase complex remains to be understood in
early developmental events. In this study, using immunocytochemical analyses, we
find that the P-TEFb components, Cyclin T1, CDK9, and its T-loop phosphorylated
form, are localized to nuclear speckles, as well as in nucleoli in mouse germinal
vesicle oocytes. Moreover, using fluorescence in situ hybridization, we show that
in absence of CDK9 activity, nucleolar integration, as well as production of 28S
rRNA is impaired in oocytes and embryos. We also present evidence indicating that
P-TEFb kinase activity is essential for completion of mouse oocyte maturation and
embryo development. Treatment with CDK9 inhibitor, flavopiridol resulted in
metaphase I arrest in maturing oocytes. Inhibition of CDK9 kinase activity did
not interfere with in vitro fertilization and pronuclear formation. However, when
zygotes or 2-cell embryos were treated with flavopiridol only in their G2 phase
of the cell cycle, development to the blastocyst stage was impaired. Inhibition
of the CDK9 activity after embryonic genome activation resulted in failure to
form normal blastocysts and aberrant phosphorylation of RNA polymerase II CTD. In
all stages analyzed, treatment with flavopiridol abrogated global transcriptional
activity. Collectively, our data suggest that P-TEFb kinase activity is crucial
for oocyte maturation, embryo development, and regulation of global RNA
transcription in mouse early development.
PMID- 27488305
TI - Patch testing of food allergens promotes Th17 and Th2 responses with increased IL
33: a pilot study.
PMID- 27488306
TI - The Sadomasochism Checklist: A Tool for the Assessment of Sadomasochistic
Behavior.
AB - Various scientific disciplines devoted to the study of sexual behavior are
concerned with the understanding of sadomasochistic (SM) practices. However, only
a fragmented body of theories, opinions, and studies is available, which limits
the systematic study of this field. Empirical studies and tools for the
assessment of SM tendencies are particularly sparse. Our aim was to develop a
comprehensive tool for the assessment of an individual's engagement in SM
practices. A comprehensive 24-item checklist of different types of SM play was
generated with the assistance of members of the German SM community, covering
both a dominance scale and a submission scale. The sadomasochism checklist was
administered in an online study to a sample of 652 adults (345 female, 307 male),
with 527 participants being active members in the SM community. Both the
frequency of SM behavior and the attraction to the types of SM practices were
assessed. Results revealed a one-factor structure for the dominance as well as
the submission scale. The distinction between different types of practices (soft
play, domination/submission, beating, toys, breath and bodily fluids) was
confirmed using principal component analysis. Cronbach's alpha was appropriate.
The total scores for the dominance and the submission scale distinguish between
participants with different preferences for dominant and submissive practices.
The newly developed scale is a reliable and valid tool for the assessment of the
frequency of and attraction to SM behavior. It aims to provide the basis for
future systematic studies on sadomasochism.
PMID- 27488307
TI - Variation in Sexual Identification Among Behaviorally Bisexual Women in the
Midwestern United States: Challenging the Established Methods for Collecting Data
on Sexual Identity and Orientation.
AB - Collecting information on sexual identity is critical to ensuring the visibility
of minority populations who face stigmatization and discrimination related to
sexual identities. However, it is challenging to capture the nuances of sexual
identity with traditional survey research methods. Using a mixed-methods
approach, we gathered data on the sexual identities of 80 behaviorally bisexual
women in the Midwestern United States through an online survey. When provided
different types of measures (e.g., open ended and fixed response) and different
contexts in which to identify (e.g., private and public), participants varied in
how they reported their sexual identities. Qualitative analysis of participant
narratives around identity change finds partitioning and ranking of attraction is
a key component in understanding behaviorally bisexual women's identities. We
further identify a division regarding the desired outcomes of identity
development processes. Given the multiple ways in which participants identified
depending upon the type of measure and the context specified, and the variation
in identification over time, results support reconsidering the capability of
typical measures and methods used in survey research to capture sexual identity
information. Additionally, findings highlight the utility of including multiple,
context-specific measures of sexual identities in future research.
PMID- 27488308
TI - [Tinea in the genital area : A diagnostic and therapeutic challenge].
AB - Pubogenital tinea or tinea genitalis represents a rare type of dermatophytosis
which, however, is increasingly being diagnosed. The mons pubis is affected, but
also the outer regions to the penis shaft and the labia together with the groins.
Pubogenital tinea is a more superficial erythrosquamous type, but strong
inflammatory dermatomycoses of the genital area as tinea genitalis profunda
ranging to kerion celsi are observed. A total of 30 patients (14-63 years of age,
11 men and 19 women) with pubogenital tinea are described. Most patients
originated from Graz, Austria, while 2 patients were from Germany (Saxony and
Isle of Sylt). Causative agents were mainly zoophilic dermatophytes: Microsporum
(M.) canis (11), Trichophyton (T.) interdigitale (9), T. anamorph of Arthroderma
benhamiae (2), and T. verrucosum (1). Anthropophilic fungi were T. rubrum (6) and
T. tonsurans (1). Anamnestic questions should include contact with pets, physical
activities, and travel. Genital shaving and concurrent tinea pedis and
onychomycosis are disposing factors. Treatment consisted of oral antifungals
except in the three women who were pregnant. Preferably, itraconazole or
terbinafine was used, while in a single case, fluconazole was administered.
Griseofulvin was not used, because this classic systemic antifungal agent is not
allowed any more in Austria. In one patient, oral antifungal therapy was changed
from itraconazole to terbinafine due to inefficacy.
PMID- 27488309
TI - A prospective study investigating the causes of warfarin under-utilization in
Chinese patients.
AB - Background Warfarin is efficacious for ischemic stroke prevention in intermediate
to high-risk patients with atrial fibrillation; thus, warfarin is the
recommended treatment according to evidence-based guidelines. Objective This
prospective study evaluated the reasons for under-utilization of warfarin in
Chinese patients with non-valvular atrial fibrillation (NVAF). Setting The
People's Hospital of Henan Province of Zhengzhou City, which is a 3900-bed
tertiary-care teaching institution. Methods We extracted data from an existing
patient database. Patients at risk for thromboembolism were categorized based on
CHA2DS2-VASc [congestive heart failure, hypertension, age >=75 (doubled),
diabetes, prior stroke (doubled), vascular disease, age 65-74 years, and sex
category (female)] scores. Main outcome measure The percent of warfarin
utilization was estimated in recruited patients. Any demographic and clinical
factors associated with warfarin under-utilization were identified using a
logistic regression model. Results Among the patient sample (n = 612), 569
patients had a CHA2DS2-VASc score of >=1. At presentation, warfarin under
utilization was estimated to be 27.1 %. Only 120 patients (25.1 %) considered to
be at the highest risk were prescribed warfarin. Binary logistic regression
analysis indicated that previous stroke, age >=75 years, and anti-platelet
therapy were associated with warfarin under-utilization. Conclusion Patients with
CHA2DS2-VASc scores >=1 who were admitted with NVAF were under prescribed
warfarin, and 138 patients were not treated with either warfarin or other
antithrombotic therapies. In conclusion, a more aggressive approach for stroke
prevention in NVAF patients is required.
PMID- 27488310
TI - Polycomb complex PRC1 as gatekeeper of intestinal stem cell identity.
AB - Intestinal stem cells (ISCs) are adult multipotent cells essential for the
maintenance of intestinal epithelial homeostasis. Wnt signaling activity ensures
that the pool of ISCs at the basis of the intestinal crypts is preserved.
Dysregulation of the Wnt pathway is often observed in cancer and supports
malignant progression. Chiacchiera and colleagues recently demonstrated the
implication of the polycomb complex PRC1 in the regulation of the Wnt pathway in
adult ISCs. The authors show that PRC1 maintains intestinal homeostasis by
repressing the expression of ZICs, a family of transcription factors inactivating
the beta-catenin/TCF complex. Importantly, interfering with PRC1 activity
completely inhibits the formation of Wnt-dependent tumors. These findings reveal
a new layer of epigenetic regulation of the Wnt pathway and open novel
opportunities for cancer stem cell targeted therapy.
PMID- 27488311
TI - Correction of penile ventral curvature in patients with minor or no hypospadias:
a single surgeon's experience of 43 cases.
AB - PURPOSE: To report our experience of correcting penile ventral curvature
associated with minor or no hypospadias. METHODS: We reviewed 43 penile ventral
curvature patients treated by a single surgeon from 1997 to 2015. Of these, 23
had minor hypospadias. Curvature was corrected using degloving, chordectomy,
dorsal plication (DP), tunica albuginea incision (TAI), or a combination of
these. Outcome was confirmed by induced artificial erection and post-operative
appearance. RESULTS: Mean age at curvature correction was 3.2 +/- 2.6 years.
17/43 had degloving and chordectomy (DC), 16/43 had DP after DC, and 10/43 had
TAI after DC, because of ventral shortening and severe curvature caused by a
short hypoplastic urethra. Other procedures required were primary meatoplasty (n
= 4) and urethroplasty (UP; n = 1) at the time of curvature correction, and UP
after correction of curvature (n = 11). Complications included recurrence of
curvature after DP (n = 3/16; 18.8 %) and urethral stenosis after UP with tubed
peritoneum (n = 1/10; 10 %). There were no recurrences of curvature in TAI cases.
Parents reported penile cosmesis as good (n = 38; 88.4 %), acceptable (n = 4; 9.3
%), or poor (n = 1; 2.3 %). CONCLUSION: We recommend TAI followed by UP for
correcting penile ventral curvature with short hypoplastic urethra. Tubed
peritoneum is not recommended for UP.
PMID- 27488313
TI - Current Treatment Strategies for Heart Failure: Role of Device Therapy and LV
Reconstruction.
AB - OPINION STATEMENT: Medical care of heart failure (HF) begins with the
determination of the cause of the heart failure and diagnosing potential
reversible causes (i.e., coronary heart disease, hyperthyroidism, etc.). Medical
therapy includes pharmacological and nonpharmacological strategies that limit
and/or reverse the signs and symptoms of HF. Initial behavior modification
includes dietary sodium and fluid restriction to avoid weight gain; and
encouraging physical activity when appropriate. Optimization of medical therapy
is the first line of treatment that includes the use of diuretics, vasodilators
(i.e., ACE inhibitors or ARBs), beta blockers, and potentially inotropic agents
and anticoagulation depending on the patient's severity of heart failure and LV
dysfunction. As heart failure advances despite optimized medical management,
cardiac resynchronization therapy (CRT), and implantable cardioverter
defibrillators (ICDs) are appropriate device therapies. The development of
progressive end-stage HF, despite maximal medical therapy, necessitates the
consideration of mechanical circulatory devices such as ventricular assist
devices (VADs) either as a bridge to heart transplantation or as destination
therapy. Despite the advances in the treatment of heart failure, there is still a
large morbidity and mortality associated with HF, thus the need to develop newer
strategies for the treatment of HF.
PMID- 27488312
TI - Generalized recovery algorithm for 3D super-resolution microscopy using rotating
point spread functions.
AB - Super-resolution microscopy with phase masks is a promising technique for 3D
imaging and tracking. Due to the complexity of the resultant point spread
functions, generalized recovery algorithms are still missing. We introduce a 3D
super-resolution recovery algorithm that works for a variety of phase masks
generating 3D point spread functions. A fast deconvolution process generates
initial guesses, which are further refined by least squares fitting. Overfitting
is suppressed using a machine learning determined threshold. Preliminary results
on experimental data show that our algorithm can be used to super-localize 3D
adsorption events within a porous polymer film and is useful for evaluating
potential phase masks. Finally, we demonstrate that parallel computation on
graphics processing units can reduce the processing time required for 3D
recovery. Simulations reveal that, through desktop parallelization, the ultimate
limit of real-time processing is possible. Our program is the first open source
recovery program for generalized 3D recovery using rotating point spread
functions.
PMID- 27488314
TI - A hepatoid carcinoma of the pancreatic head.
AB - Hepatoid carcinoma (HC) is an extremely rare form of neoplasm. Its cellular
structure resembles that of a hepatocellular carcinoma (HCC). To date, only 26
cases of hepatoid carcinoma of the pancreas have been reported in the literature.
We report the diagnosis of a hepatoid carcinoma of the pancreatic head in a 78
year-old male patient. The tumor was detected incidentally during routine
abdominal ultrasound scanning. Laboratory tests did not show any abnormalities
except for a monoclonal gammopathy of undetermined significance. After CT, MRI,
and laparoscopic biopsy that failed to obtain the diagnosis, the patient
underwent a Whipple procedure. The final pathology report described a hepatoid
carcinoma of the pancreatic head (pathological T3, N0 (0/10), L0, V0, R0, M0).
After the patient recovered, no further therapy was recommended by the tumor
board and he was discharged. Regular follow-up was suggested; however, the
patient suddenly died of acute coronary artery disease 2 months after surgery.
PMID- 27488315
TI - Mass Spectrometry Based Mechanistic Insights into Formation of Tris Conjugates:
Implications on Protein Biopharmaceutics.
AB - We present here extensive mass spectrometric studies on the formation of a Tris
conjugate with a therapeutic monoclonal antibody. The results not only
demonstrate the reactive nature of the Tris molecule but also the sequence and
reaction conditions that trigger this reactivity. The results corroborate the
fact that proteins are, in general, prone to conjugation and/or adduct formation
reactions and any modification due to this essentially leads to formation of
impurities in a protein sample. Further, the results demonstrate that the
conjugation reaction happens via a succinimide intermediate and has sequence
specificity. Additionally, the data presented in this study also shows that the
Tris formation is produced in-solution and is not an in-source phenomenon. We
believe that the facts given here will open further avenues on exploration of
Tris as a conjugating agent as well as ensure that the use of Tris or any ionic
buffer in the process of producing a biopharmaceutical drug is monitored closely
for the presence of such conjugate formation. Graphical Abstract ?.
PMID- 27488316
TI - The Development of Novel Nanodiamond Based MALDI Matrices for the Analysis of
Small Organic Pharmaceuticals.
AB - The utility of novel functionalized nanodiamonds (NDs) as matrices for matrix
assisted laser desorption ionization-mass spectrometry (MALDI-MS) is described
herein. MALDI-MS analysis of small organic compounds (<1000 Da) is typically
complex because of interferences from numerous cluster ions formed when using
conventional matrices. To expand the use of MALDI for the analysis of small
molecules, novel matrices were designed by covalently linking conventional
matrices (or a lysine moiety) to detonated NDs. Four new functionalized NDs were
evaluated for their ionization capabilities using five pharmaceuticals with
varying molecular structures. Two ND matrices were able to ionize all tested
pharmaceuticals in the negative ion mode, producing the deprotonated ions [M -
H](-). Ion intensity for target analytes was generally strong with enhanced
signal-to-noise ratios compared with conventional matrices. The negative ion mode
is of great importance for biological samples as interference from endogenous
compounds is inherently minimized in the negative ion mode. Since the molecular
structures of the tested pharmaceuticals did not suggest that negative ion mode
would be preferable, this result magnifies the importance of these findings. On
the other hand, conventional matrices primarily facilitated the ionization as
expected in the positive ion mode, producing either the protonated molecules [M +
H](+) or cationic adducts (typically producing complex spectra with numerous
adduct peaks). The data presented in this study suggests that these matrices may
offer advantages for the analysis of low molecular weight
pharmaceuticals/metabolites. Graphical Abstract ?.
PMID- 27488317
TI - Ion Mobility-Mass Spectrometry as a Tool for the Structural Characterization of
Peptides Bearing Intramolecular Disulfide Bond(s).
AB - Disulfide bonds are post-translationnal modifications that can be crucial for the
stability and the biological activities of natural peptides. Considering the
importance of these disulfide bond-containing peptides, the development of new
techniques in order to characterize these modifications is of great interest. For
this purpose, collision cross cections (CCS) of a large data set of 118 peptides
(displaying various sequences) bearing zero, one, two, or three disulfide bond(s)
have been measured in this study at different charge states using ion mobility
mass spectrometry. From an experimental point of view, CCS differences (DeltaCCS)
between peptides bearing various numbers of disulfide bonds and peptides having
no disulfide bonds have been calculated. The DeltaCCS calculations have also been
applied to peptides bearing two disulfide bonds but different cysteine
connectivities (Cys1-Cys2/Cys3-Cys4; Cys1-Cys3/Cys2-Cys4; Cys1-Cys4/Cys2-Cys3).
The effect of the replacement of a proton by a potassium adduct on a peptidic
structure has also been investigated. Graphical Abstract ?.
PMID- 27488318
TI - Hepatitis c eradication: It's now or never...let's get to work.
PMID- 27488319
TI - Is endoscopic papillary large balloon dilation safe for treating large CBD
stones?
AB - In recent years, endoscopic papillary large balloon dilation (EPLBD) with
endoscopic sphincterotomy (EST) has been shown to be an effective technique for
the removal of large or difficult common bile duct (CBD) stones, as an
alternative to EST. Reviewing the literature published since 2003, it is
understood that EPLBD has fewer associated overall complications than EST.
Bleeding occurred less frequently with EPLBD than with EST. There was no
significant difference in postendoscopic retrograde cholangiopancreatography
pancreatitis or perforation. Recent accumulated results of EPLBD with or even
without EST suggest that it is a safe and effective procedure for the removal of
large or difficult bile duct stones without any additional risk of severe adverse
events, when performed under appropriate guidelines. Since use of a larger
balloon can tear the sphincter as well as the bile duct, possibly resulting in
bleeding and perforation, a balloon size that is equal to or smaller in diameter
than the diameter of the native distal bile duct is recommended. The maximum
transverse diameter of the stone and the balloon-stone diameter ratio have a
tendency to affect the success or failure of complete removal of stones by large
balloon dilation to prevent adverse effects such as perforation and bleeding. One
should take into account the size of the native bile duct, the size and burden of
stones, the presence of stricture of distal bile duct, and the presence of the
papilla in or adjacent to a diverticulum. Even though the results of EPLBD
indicate that it is a relatively safe procedure in patients with common duct
stones with a dilated CBD, the recommended guidelines should be followed strictly
for the prevention of major adverse events such as bleeding and perforation.
PMID- 27488320
TI - Neurokinin-1 receptor antagonists as antitumor drugs in gastrointestinal cancer:
A new approach.
AB - Gastrointestinal (GI) cancer is the term for a group of cancers affecting the
digestive system. After binding to the neurokinin-1 (NK-1) receptor, the
undecapeptide substance P (SP) regulates GI cancer cell proliferation and
migration for invasion and metastasis, and controls endothelial cell
proliferation for angiogenesis. SP also exerts an antiapoptotic effect. Both SP
and the NK-1 receptor are located in GI tumor cells, the NK-1 receptor being
overexpressed. By contrast, after binding to the NK-1 receptor, NK-1 receptor
antagonists elicit the inhibition (epidermal growth factor receptor inhibition)
of the proliferation of GI cancer cells in a concentration-dependent manner,
induce the death of GI cancer cells by apoptosis, counteract the Warburg effect,
inhibit cancer cell migration (counteracting invasion and metastasis), and
inhibit angiogenesis (vascular endothelial growth factor inhibition). NK-1
receptor antagonists are safe and well tolerated. Thus, the NK-1 receptor could
be considered as a new target in GI cancer and NK-1 receptor antagonists (eg,
aprepitant) could be a new promising approach for the treatment of GI cancer.
PMID- 27488321
TI - Epidemiology, disease burden, and treatment strategies of chronic hepatitis C
virus infections in Saudi Arabia in the new treatment paradigm shift.
AB - BACKGROUND/AIMS: Around 101,000 individuals are estimated to be viremic for
chronic hepatitis C virus (HCV) in the Kingdom of Saudi Arabia (KSA) in 2014;
however, only about 20% have been diagnosed. We aim to assess baseline
epidemiology, disease burden, and evaluate strategies to eliminate HCV in KSA.
MATERIALS AND METHODS: The infected population and disease progression were
modeled using age- and gender-defined cohorts to track HCV incidence, prevalence,
hepatic complications, and mortality. Baseline assumptions and transition
probabilities were extracted from the literature. The impacts of two scenarios on
HCV-related disease burden were considered through increases in treatment
efficacy alone or treatment and diagnosis. RESULTS: In 2030, it is estimated by
the base scenario that viremic prevalence will increase to 103,000 cases,
hepatocellular carcinoma (HCC) to 470, decompensated and compensated cirrhosis
cases to 1,300 and 15,400, respectively, and liver-related mortality to 670
deaths. Using high efficacy treatment alone resulted in 2030 projection of 80,700
viremic cases, 350 HCC cases, 480 liver-related deaths, and 850 and 11,500
decompensated and compensated cirrhosis cases, respectively. With an aggressive
treatment strategy, in 2030 there will be about 1,700 viremic cases, 1 HCC case,
about 20 liver-related deaths, and 5 and 130 cases of decompensated and
compensated cirrhosis, respectively. Delaying this strategy by one year would
result in 360 additional deaths by 2030. CONCLUSIONS: HCV in KSA remains
constant, and cases of advanced liver disease and mortality continue to rise.
Considered increases in treatment efficacy and number treated would have a
significantly greater impact than increased treatment efficacy alone. The
projected impact will facilitate disease forecasting, resource planning, and
strategies for HCV management. Increased screening and diagnosis would likely be
required as part of a national strategy.
PMID- 27488322
TI - A quick screening model for symptomatic bacterascites in cirrhosis.
AB - BACKGROUND: Diagnosis of spontaneous bacterial peritonitis in cirrhosis can be
made when a patient has an ascites polymorphonuclear leukocyte count >=250/mm3.
However, symptomatic bacterascites, which is a variant of spontaneous bacterial
peritonitis with signs of infection but an ascites polymorphonuclear leukocyte
count <250/mm3, cannot be confirmed until the time-consuming ascites culture
becomes positive. Currently, early indicators for symptomatic bacterascites
remain undetermined. AIMS: To develop a quick screening model for early detection
of symptomatic bacterascites in cirrhosis. MATERIALS AND METHODS: Data on
patients with cirrhotic ascites from two hospitals (from 2010 to 2014) were
collected retrospectively. Patients with symptomatic bacterascites were enrolled
in the case group and compared with patients without any infection in the control
group. Logistic regression analysis was used to build a model for screening
symptomatic bacterascites, and a receiver operating characteristics curve was
used to assess the model. RESULTS: In total, 103 patients were enrolled in the
case group and 204 patients were enrolled in the control group. A screening model
was constructed based on body temperature, abdominal tenderness, blood neutrophil
percentage, blood total bilirubin, prothrombin time, and ascites nucleated
leukocyte count. The area under the receiver operating characteristic curve was
0.939; a screening score of 0.328 was the best cutoff value. CONCLUSION: Patients
with suspected symptomatic bacterascites can be quickly screened according to the
developed model, and a screening score >=0.328 indicates symptomatic
bacterascites.
PMID- 27488323
TI - Significance of BMI1 and FSCN1 expression in colorectal cancer.
AB - BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer
in terms of incidence and the fourth in cause of death world-wide, underscoring
the need to identify novel biomarkers for early diagnosis, as well as improved
disease stratification and treatment choices. PATIENTS AND METHODS: The Gene
Expression Omnibus (GSE21510) and the Cancer Genome Atlas (TCGA) CRC datasets
were utilized in the current study. GeneSpring 13.0 was used for normalization
and analysis. The log-rank test was used to compare the outcome between
expression groups. RESULT: Significant upregulation of BMI1 (2.3 FC, P = 3.7 * 10
18) and FSCN1 (1.3 FC,P = 4.7 * 10-3) was observed in CRC. High BMI1 expression
was associated with reduced overall survival (OS) [Hazard ratio (HR), 1.87; 95%
CI. 1.17-3.03; P= 0.009] and reduced disease-free survival (DFS) [HR, 162; 95% CI
1.01-2.63;P = 0.045]. Similarly, high expression of FSCN1 was associated with
reduced OS (HR, 2.0; 95% CI, 1.24-3.2; P= 0.0044) and reduced DFS (HR, 1.60; 95%
CI, 0.99-2.57;P = 0.055). Importantly, BMI1high/FSCN1high patients experienced
the worst OS (HR, 3.17; 95% CI, 1.77-6.15; P= 0.0002) and DFS (HR, 2.34; 95% CI,
1.27-4.67,P = 0.0078). Using pathway analyses, tumors overexpressing BMI1 were
enriched in zinc finger proteins and genes involved in DNA binding and regulation
of transcription, whereas tumors expressing FSCN1 were enriched in genes involved
in cell migration. CONCLUSION: Our data revealed poor OS and DFS in CRC patients
overexpressing BMI1 or FSCN1 and suggest that these two markers in combination
may represent superior prognostic marker to either one. Targeting BMI1 and FSCN1
may also provide potential therapeutic opportunity in CRC.
PMID- 27488325
TI - Catheter-related blood stream infection in patients receiving long-term home
parenteral nutrition: Tertiary care hospital experience in Saudi Arabia.
AB - BACKGROUND/AIM: Parenteral nutrition (PN) is a lifesaving therapy for patients
with many severe conditions, including intestinal failure. Some patients require
long-term PN therapy, which makes home parenteral nutrition (HPN) an attractive
option to improve the quality of life. Among the most common and serious
complications observed in these patients are catheter-related blood stream
infections (CRBSIs). The aim of our study is to determine the frequency of CRBSI
among patients receiving long-term HPN. PATIENTS AND METHODS: A retrospective
chart review was conducted for patients enrolled in the HPN program between 2006
and 2012. Data on the demographic characteristics, indications and duration of PN
therapy, catheter type, number of admissions because of CRBSI, and blood culture
results were recorded. RESULTS: Eight pediatric patients were included (mean age
of 3.5 years at the start of HPN). Microvillus inclusive disease was noted in 50%
of these patients, and 75% of them received HPN under parents' care. CRBSI
resulted in 60 admissions with a median of 182 days of hospital stay and 74
changes of central venous catheters. The rate of CRBSI was 2.9 per 1000 catheter
days. Staphylococcus species were the most prevalent pathogens (32%), followed by
Klebsiella pneumoniae (5%). CONCLUSION: In this small group of HPN patients, the
BSI rate was 2.9 infections per 1000 catheter days, and most common causative
organisms were Staphylococcus species. We believe that a well-established
training program for caregivers can reduce the rate of infectious complications
associated with long-term PN support.
PMID- 27488324
TI - Transient elastography in clinical detection of liver cirrhosis: A systematic
review and meta-analysis.
AB - BACKGROUND/AIMS: Transient elastography is a noninvasive method for measuring
liver fibrosis. This meta-analysis assesses the diagnostic performance of
transient elastography of detecting liver cirrhosis in patients with liver
disease. PATIENTS AND METHODS: We searched MEDLINE, Cochrane, EMBASE databases
until Jan 31, 2015, using the following search terms: elastography and liver
cirrhosis. Included studies assessed patients with a diagnosis of liver
cirrhosis, with an index test of transient elastography, and with the reference
standard being a histopathological exam by liver biopsy. Sensitivity analysis and
assessment of risk of bias and publication bias were performed. RESULTS: Fifty
seven studies were included in the meta-analysis with a total of 10,504 patients.
The pooled estimate for the sensitivity of transient elastography for detecting
liver fibrosis was 81% and the specificity was 88%. The imputed diagnostic odds
ratio (DOR) was 26.08 and the area under the receiver-operating characteristic
(AUROC) curve was 0.931. CONCLUSION: Our findings indicate that transient
elastography shows good sensitivity, specificity and a high accuracy for
detecting liver cirrhosis. Transient elastography can be used as an additional
method for the clinical diagnosis of liver fibrosis and cirrhosis.
PMID- 27488326
TI - Sequential versus concomitant therapy for eradication of Helicobacter Pylori in
patients with perforated duodenal ulcer: A randomized trial.
AB - OBJECTIVES: Comparison of Helicobacter pylori eradication rates, side effects,
compliance, cost, and ulcer recurrence of sequential therapy (ST) with that of
concomitant therapy (CT) in patients with perforated duodenal ulcer following
simple omental patch closure. METHODS: Sixty-eight patients with perforated
duodenal ulcer treated with simple closure and found to be H. pylori positive on
three months follow-up were randomized to receive either ST or CT for H. pylori
eradication. Urease test and Giemsa stain were used to assess for H. pylori
eradication status. Follow-up endoscopies were done after 3 months, 6 months, and
1 year to evaluate the ulcer recurrence. RESULTS: H. pylori eradication rates
were similar in ST and CT groups on intention-to-treat (ITT) analysis (71.43% vs
81.80%,P = 0.40). Similar eradication rates were also found in per-protocol (PP)
analysis (86.20% vs 90%,P = 0.71). Ulcer recurrence rate in ST groups and CT
groups at 3 months (17.14% vs 6.06%,P = 0.26), 6 months (22.86% vs 9.09%,P =
0.19), and at 1 year (25.71% vs 15.15%,P = 0.37) of follow-up was also similar by
ITT analysis. Compliance and side effects to therapies were comparable between
the groups. The most common side effects were diarrhoea and metallic taste in ST
and CT groups, respectively. A complete course of ST costs Indian Rupees (INR)
570.00, whereas CT costs INR 1080.00. CONCLUSION: H. pylori eradication rates,
side effects, compliance, cost, and ulcer recurrences were similar between the
two groups. The ST was more economical compared with CT.
PMID- 27488327
TI - A randomized controlled trial on the effect of vitamin D3 on inflammation and
cathelicidin gene expression in ulcerative colitis patients.
AB - BACKGROUND: Inflammatory bowel disease (IBD) is an intestinal chronic
inflammatory condition and includes Crohn's disease (CD) and ulcerative colitis
(UC). It has been proposed that Vitamin D supplementation may have a beneficial
role in IBD. AIM: To characterize the effects of Vitamin D on cathelicidin
(hCAP/LL37) gene expression, ESR, and serum hs-CRP levels. MATERIALS AND METHODS:
Ninety UC patients on remission were randomized to receive 300,000 IU
intramuscular Vitamin D or 1 mL normal saline as placebo, respectively. Before
and 90 days after intervention, serum levels of 25 (OH)-Vitamin D3, PTH, Calcium,
ESR, and hs-CRP were measured. Cathelicidin gene expression was also quantified
using qRT-PCR. RESULTS: Baseline serum 25-OH-Vitamin D3 levels were not different
between the two groups and after intervention, increased only in Vitamin D group
(P < 0.001). Hs-CRP levels were lower in Vitamin D group after intervention
(Before: 3.43 +/- 3.47 vs 3.86 +/- 3.55 mg/L, P = 0.56; after: 2.31 +/- 2.25 vs
3.90 +/- 3.97 mg/L, P= 0.023). ESR decreased significantly in Vitamin D group
(Before: 12.4 +/- 6.1 vs 12.1 +/- 5.3 mm/h, P= 0.77; after: 6.7 +/- 4.5 vs 11.4
+/- 5.5 mm/h, P< 0.001). The mean fold change in hCAP18 gene expression in
Vitamin D group was significantly higher than placebo group. (Mean +/- SD: 3.13
+/- 2.56 vs 1.09 +/- 0.56; median +/- interquartile range: 2.17 +/- 3.81 vs 0.87
+/- 0.53, P< 0.001). CONCLUSION: Decreases in ESR and hs-CRP levels and increase
in LL37 gene expression support the hypothesis that Vitamin D supplementation may
have a beneficial role in UC patients.
PMID- 27488329
TI - The LMS and Z scale growth reference for Saudi school-age children and
adolescents.
AB - BACKGROUND/AIM: To establish L, M, and S parameters and z score reference for the
assessment of nutrition and growth of Saudi school-age children and adolescents.
SUBJECTS AND METHODS: Data from the original cross-sectional study were
reanalyzed. The L, M, and S parameters and z scores were calculated for weight,
height and body mass index for school-age children and adolescents. RESULTS: A
total of 19,299 subjects from 5 to 18 years of age were included. All were Saudi
nationals and 9,827 (50.9%) were boys. The L M S parameters and z scores for
weight for age, height for age, and BMI for age for boys and girls are presented
in detailed tables across the age of commonly used z scores (+3, +2, +1, 0, -1,
2, -3). Graphs corresponding to the same parameters (weight, height, and BMI)
showing the main z scores across all ages from 5 to 18 years are illustrated.
CONCLUSION: This report provides the first reference for nutritional status and
growth of Saudi school-age children and adolescents. This tool is essential for
more accurate assessment of growth and nutrition in various clinical conditions
and research.
PMID- 27488328
TI - New combined parameter of liver and splenic stiffness as determined by
elastography in healthy volunteers.
AB - BACKGROUND: The diagnosis of chronic liver disease (CLD) leading to fibrosis,
cirrhosis, and portal hypertension had witnessed dramatic changes after the
introduction of noninvasive figure accessible tools over the past few years.
Imaging techniques that are based on evaluation of the liver stiffness was
particularly useful in this respect. Acoustic radiation force impulse (ARFI)
emerged as an interesting figure tool with reliable repute and high precision.
AIMS: To evaluate liver stiffness measurement (LSM) and splenic stiffness
measurement (SSM) in healthy volunteers as concluded by the ARFI technique and to
out a numeric calculated ratio that may reflect their correlation in the
otherwise healthy liver. PATIENTS AND METHODS: A ratio (splenic stiffness/liver
stiffness in kPa) was determined in 207 consenting healthy subjects and was
investigated with respect to age, gender, ethnic origin, body mass index (BMI),
liver and spleen sizes healthy volunteers, alanine aminotransferase (ALT),
aspartate aminotransferase (AST), platelet count (PLT), APRI, and FIB-4 scores.
RESULTS: Data from this work led to computing an index of 4.72 (3.42-7.33) in
healthy persons on an average. Females had a higher index than males 6.37 vs
4.92, P=0.002. There was not any significant difference of the ratio in different
age groups; ethnic origins; any correlation between SSM/LSM ratio and BMI; liver
and spleen sizes; or ALT, AST, PLT, APRI, and FIB-4 scores. CONCLUSIONS: A
quantifiable numeric relationship between splenic and liver stiffness in the
healthy subjects could be computed to a parameter expressed as SSM/LSM ratio. We
believe that this ratio can be a useful reference tool for further researches in
CLD.
PMID- 27488330
TI - Endoscopic ultrasound-guided antegrade stenting in an occluded biliary self
expandable metal stent.
AB - Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an attractive option
for patients who cannot undergo conventional endoscopic retrograde
cholangiopancreatography (ERCP) and do not want surgery or percutaneous drainage
procedures. We present the use of EUS-antegrade (EUS-AG) insertion of a self
expandable metal stent (SEMS) in a patient with a common hepatic duct
cholangiocarcinoma, as well as a huge gastric lipoma, after recurrent biliary
obstruction of a prior SEMS inserted via ERCP in the same session as a duodenal
stent insertion for gastric outlet obstruction.
PMID- 27488331
TI - Impact of pediatric inflammatory bowel disease on linear growth: Data from a
national cohort study in Saudi Arabia.
PMID- 27488332
TI - From legacy to novel: vidian neurectomy and eustachian tube balloon dilatation in
modern ENT practice.
PMID- 27488333
TI - Balloon dilation for eustachian tube dysfunction: systematic review.
AB - BACKGROUND: Eustachian tube dysfunction is a disorder for which there are limited
medical and surgical treatments. Recently, eustachian tube balloon dilation has
been proposed as a potential solution. METHOD: A systematic literature review was
performed. Abstracts were selected for relevance, and pooled data analysis and
qualitative analysis was conducted. RESULTS: Nine prospective studies, describing
713 eustachian tube balloon dilations in 474 patients (aged 18-86 years), were
identified. Follow-up duration ranged from 1.5 to 18 months. Ability to perform a
Valsalva manoeuvre improved from 20 to 177 out of 245 ears following eustachian
tube balloon dilation and, where data were reported in terms of patient numbers,
from 15 to 189 out of 210 patients. Tympanograms were classified as type A in 7
out of 141 ears pre-operatively and in 86 out of 141 ears post-operatively.
CONCLUSION: Prospective case series can confirm the safety of eustachian tube
balloon dilation. As a potential solution for chronic eustachian tube
dysfunction, further investigations are warranted to establish a higher level of
evidence of efficacy.
PMID- 27488334
TI - Open and endovascular repair of aneurysms affecting the distal extracranial
internal carotid artery: case series.
AB - OBJECTIVE: Three cases of internal carotid artery aneurysm affecting the distal
cervical segment were retrospectively reviewed. METHODS: Two patients underwent
open surgical repair requiring petrous segment exposure for bypass of the
affected segment using a Fisch type A lateral skull base approach. The third
patient underwent endovascular stenting. RESULTS: There were no cerebrovascular
complications post-operatively. Both open repair patients experienced temporary
lower cranial nerve palsies. One required facial nerve grafting. All patients had
patent grafts at follow up. The stent graft patient had a small endoleak at six
months. CONCLUSION: Endovascular and open approaches both have advantages and
disadvantages. Treatment needs to be tailored to the lesion and the patient. An
open surgical approach is difficult but well established. Endovascular treatment
of these lesions is a relatively recent technique, and new cases need to be
continually reported with a view to attaining long-term data.
PMID- 27488335
TI - The role of subtotal petrosectomy in cochlear implantation.
AB - BACKGROUND: Subtotal petrosectomy combined with cochlear implantation is a
procedure required in specific situations. METHODS: A retrospective review of all
cases of subtotal petrosectomy in cochlear implant surgery over a five-year
period was performed. The indications, complications and outcomes for this
procedure are outlined. RESULTS: Sixteen patients underwent cochlear implantation
in combination with subtotal petrosectomy and blind sac closure of the external
auditory meatus from 2008 to 2013. Seventy-five per cent of these were completed
as a two-stage procedure and 25 per cent as a single-stage procedure. The most
common indications for the procedure were chronic otitis media, previous radical
cavity, and for surgical access in challenging anatomy or in drill-out
procedures. Mastoids were obliterated with fat or musculoperiosteal flaps. The
complication rate relating to blind sac closure was 6 per cent. Cochlear implants
were successfully placed in all cases and there was no incidence of device
failure. CONCLUSION: For patients with chronic suppurative otitis media or
existing mastoid cavities, subtotal petrosectomy with blind sac closure of the
external auditory canal, closure of the eustachian tube, and cavity obliteration
is an effective technique to facilitate safe cochlear implantation.
PMID- 27488336
TI - Wide anterior neck dissection for management of recurrent thyroglossal duct cysts
in adults.
AB - OBJECTIVE: Thyroglossal duct cyst recurrence following resection is attributed to
anatomical variability and residual thyroglossal ducts. In adults, thyroglossal
duct cyst recurrence is extremely rare and a surgical solution is yet to be well
explored. This paper describes our approach to the management of recurrent
thyroglossal duct cysts and sinuses in adults using a wide anterior neck
dissection. METHOD: A retrospective review was performed to identify adults who
underwent a wide anterior neck dissection for recurrent thyroglossal duct cyst
management between 1 January 2009 and 1 January 2015. RESULTS: Six males and one
female were included in the series (mean age, 26.4 +/- 10.9 years). Recurrence
occurred at a mean of 18 +/- 9.8 months following primary surgical management (3
patients underwent cystectomy and 4 had a Sistrunk procedure). All patients
subsequently underwent wide anterior neck dissection; there was no further
recurrence over the 12-month average follow-up period. CONCLUSION: This paper
describes a wide anterior neck dissection technique for the management of
recurrent thyroglossal duct cysts or sinuses in adults; this approach addresses
the variable anatomy of the thyroglossal duct and is associated with minimal
morbidity.
PMID- 27488337
TI - Synchronous or metachronous lymphoma and metastatic cutaneous squamous cell
carcinoma in the head and neck region: a diagnostic and management dilemma.
AB - OBJECTIVE: To review our experience of managing patients with a dual diagnosis of
metastatic cutaneous squamous cell carcinoma in the head and neck region and low
grade non-Hodgkin lymphoma. The secondary aim was to evaluate the utility of 18F
fluorodeoxyglucose positron emission tomography during diagnosis. METHODS:
Patients diagnosed with metastatic cutaneous squamous cell carcinoma of the head
and neck and low-grade non-Hodgkin lymphoma, in a five-year period, were
identified. Patient, tumour and treatment characteristics were identified. 18F
fluorodeoxyglucose positron emission tomography imaging was reviewed and
correlated with histopathology findings. RESULTS: Eight patients were identified.
There was a delay in diagnosis of metastatic squamous cell carcinoma in two
patients. 18F-fluorodeoxyglucose positron emission tomography differentiated
metastatic squamous cell carcinoma from low-grade non-Hodgkin lymphoma with a
sensitivity of 88.2 per cent and a specificity of 94.7 per cent. In 38 per cent
of patients, compromises in management had to be made. CONCLUSION: The management
of metastatic squamous cell carcinoma can be challenging in patients with low
grade non-Hodgkin lymphoma. 18F-fluorodeoxyglucose positron emission tomography
can be useful in the diagnosis of metastatic squamous cell carcinoma in patients
with low-grade non-Hodgkin lymphoma.
PMID- 27488338
TI - Elevated serum thyroglobulin levels at the time of ablative radioactive iodine
therapy indicate a worse prognosis in thyroid cancer: an Australian retrospective
cohort study.
AB - BACKGROUND: Serum thyroglobulin is used as a surrogate marker for well
differentiated thyroid carcinoma recurrence. This study investigates whether
thyroglobulin measured at the time of ablative radioactive iodine therapy
predicts disease-free survival. METHODS: A retrospective review was conducted of
patients with well-differentiated thyroid carcinoma presenting from 1989 to 2010
at the Royal Prince Alfred Hospital, New South Wales, Australia. Disease-free
survival of patients with a significantly elevated stimulated thyroglobulin level
(27.5 ug/l or higher) at the time of ablative radioactive iodine therapy was
compared to that of patients without a significantly elevated thyroglobulin level
using univariate analysis. RESULTS: Patients with a thyroglobulin level of 27.5
ug/l or higher had an increased relative risk of disease recurrence of 4.50 (95
per cent confidence interval = 1.35-15.04). If lateral neck dissection was
required at the time of surgery, patients also had an increased relative risk of
macroscopic disease recurrence of 4.94 (95 per cent confidence interval = 1.47
16.55). CONCLUSION: An elevated thyroglobulin level of 27.5 ug/l or higher at the
time of ablative radioactive iodine therapy is a prognostic indicator for
macroscopic disease recurrence in well-differentiated thyroid carcinoma.
PMID- 27488339
TI - Role of neck dissection in metastatic squamous cell carcinoma to the parotid
gland.
AB - OBJECTIVE: To investigate the rate of occult neck disease in patients with
metastatic squamous cell carcinoma to the parotid gland following parotidectomy
and neck dissection. METHODS: A consecutive series of patients treated between
2000 and 2014 for metastatic squamous cell carcinoma to the parotid were
analysed. Patients were included if they had no clinical or radiological evidence
of neck disease. Pathology of parotidectomy and neck dissection specimens was
reviewed. Other variables analysed included patient immune status, surgery type,
complications, use of positron emission tomography scanning and treatment with
radiotherapy. RESULTS: Sixty-five patients had no clinical or radiological
evidence of neck disease initially. Forty-six patients (70.8 per cent) underwent
neck dissection. Occult neck disease was only found in 8 of the 46 patients (17.3
per cent). Occult neck disease was found more often in those with
immunocompromise (5.7 vs 38.5 per cent, p = 0.003). Patients who were
immunocompromised had a significantly worse disease-specific survival rate at
five years (0 vs 92 per cent, p = 0.0001). CONCLUSION: Occult neck disease was
seen in 17.3 per cent of patients and immunosuppression was a significant
predictor for this.
PMID- 27488340
TI - Melioidosis in a patient with chronic rhinosinusitis.
AB - BACKGROUND: Melioidosis is a serious infection caused by soil-dwelling Gram
negative bacillus Burkholderia pseudomallei. It is most commonly reported in
Northern Australia, Southeast and Southern Asia, China, and Taiwan. METHODS: A
case report and short review of the literature are presented. Presentation,
diagnosis including genomic sequencing, and acute and long-term management are
discussed. RESULTS: A 58-year-old female presented with chronic rhinosinusitis
secondary to melioidosis. This is the third reported incidence of sinusitis
secondary to melioidosis, which occurred in an otherwise well female with no risk
factors and no apparent cause of exposure. Treatment involved an acute phase in
which meropenem was administered parenterally for two weeks, followed by a
prolonged oral course of trimethoprim-sulfamethoxazole for three months, as per
recommended guidelines. CONCLUSION: In patients presenting with refractory
chronic rhinosinusitis, ENT surgeons should consider the presence of unusual
causative pathogens such as B pseudomallei, particularly in those with recent
travel history to Northern Queensland and/or Southeast Asia.
PMID- 27488341
TI - A systematic review of the evidence base for vidian neurectomy in managing
rhinitis.
AB - BACKGROUND: Vidian neurectomy has been proposed as a surgical option for rhinitis
refractory to medical treatment. However, the evidence base for its benefit
remains controversial. METHODS: A systematic review was performed. Studies
reporting original data on patients with rhinitis treated by vidian neurectomy
were included. Patient-reported outcome measures were the primary outcome
investigated; specific peri-operative morbidities were the secondary outcome.
RESULTS: A total of 1012 articles fulfilled the search criteria, 32 of which were
included in the study. Patient-reported outcome measures were compared before and
after surgery in eight studies. There were 529 patients represented in these
trials. Significant improvement in rhinorrhoea was reported in all eight studies.
Temporary dry eyes was reported in 24.63 per cent of cases (272 out of 1104
cases). There was no report of cranial nerve deficit or eye movement disturbance.
CONCLUSION: Endoscopic vidian neurectomy does have a role in the surgical
management of refractory rhinitis, particularly in patients with non-allergic
rhinitis, but a well-designed cohort trial would be advantageous to clarify long
term outcomes.
PMID- 27488342
TI - Fluidized Bed Hot Melt Granulation with Hydrophilic Materials Improves Enalapril
Maleate Stability.
AB - This work aimed at developing enalapril maleate granules in order to improve its
stability in solid dosage form. Granules were prepared by hot melt granulation
using a fluidized bed apparatus. Gelucire 50/13(r), polyethylene glycol 6000 e
Poloxamer 407(r) were studied and compared as binders in 2 * 2 factorial designs
where the proportions of enalapril maleate, binders and spray dried lactose were
varied. The granulation process resulted in high yields and granule sizes that
indicated the prevalence of particles coating. Furthermore, the granules obtained
showed adequate flowability and a fast dissolution rate of enalapril maleate with
almost 100% of the drug released in 10 min. The stability of enalapril maleate in
hard gelatin capsules showed that the drug stability was greatly increased in
granules, since for raw drug, the remaining content of enalapril maleate after 91
days was 68.4% and, for granules, the content was always above 93%. This result
was confirmed by the quantification of the degradation products, enalaprilat and
diketopiperazine, which were found in very low content in granules samples. The
results demonstrate that fluidized bed hot melt granulation with hydrophilic
binders is a suitable alternative for improving the chemical stability of
enalapril maleate.
PMID- 27488343
TI - Integrated paediatric fever management and antibiotic over-treatment in Malawi
health facilities: data mining a national facility census.
AB - BACKGROUND: There are growing concerns about irrational antibiotic prescription
practices in the era of test-based malaria case management. This study assessed
integrated paediatric fever management using malaria rapid diagnostic tests (RDT)
and Integrated Management of Childhood Illness (IMCI) guidelines, including the
relationship between RDT-negative results and antibiotic over-treatment in Malawi
health facilities in 2013-2014. METHODS: A Malawi national facility census
included 1981 observed sick children aged 2-59 months with fever complaints.
Weighted frequencies were tabulated for other complaints, assessments and
prescriptions for RDT-confirmed malaria, IMCI-classified non-severe pneumonia,
and clinical diarrhoea. Classification trees using model-based recursive
partitioning estimated the association between RDT results and antibiotic over
treatment and learned the influence of 38 other input variables at patient-,
provider- and facility-levels. RESULTS: Among 1981 clients, 72 % were tested or
referred for malaria diagnosis and 85 % with RDT-confirmed malaria were
prescribed first-line anti-malarials. Twenty-eight percent with IMCI-pneumonia
were not prescribed antibiotics (under-treatment) and 59 % 'without antibiotic
need' were prescribed antibiotics (over-treatment). Few clients had respiratory
rates counted to identify antibiotic need for IMCI-pneumonia (18 %). RDT-negative
children had 16.8 (95 % CI 8.6-32.7) times higher antibiotic over-treatment odds
compared to RDT-positive cases conditioned by cough or difficult breathing
complaints. CONCLUSIONS: Integrated paediatric fever management was sub-optimal
for completed assessments and antibiotic targeting despite common compliance to
malaria treatment guidelines. RDT-negative results were strongly associated with
antibiotic over-treatment conditioned by cough or difficult breathing complaints.
A shift from malaria-focused 'test and treat' strategies toward 'IMCI with
testing' is needed to improve quality fever care and rational use of both anti
malarials and antibiotics in line with recent global commitments to combat
resistance.
PMID- 27488344
TI - Global transcriptional start site mapping in Geobacter sulfurreducens during
growth with two different electron acceptors.
AB - Geobacter sulfurreducens is an anaerobic soil bacterium that is involved in
biogeochemical cycles of elements such as Fe and Mn. Although significant
progress has been made in the understanding of the electron transfer processes in
G. sulfurreducens, little is known about the regulatory mechanisms involved in
their control. To expand the study of gene regulation in G. sulfurreducens, we
carried out a genome-wide identification of transcription start sites (TSS) by
5'RACE and by deep RNA sequencing of primary mRNAs in two growth conditions. TSSs
were identified along G. sulfurreducens genome and over 50% of them were located
in the upstream region of the associated gene, and in some cases we detected
genes with more than one TSS. Our global mapping of TSSs contributes with
valuable information, which is needed for the study of transcript structure and
transcription regulation signals and can ultimately contribute to the
understanding of transcription initiation phenomena in G. sulfurreducens.
PMID- 27488345
TI - Alpha-7 Nicotinic Receptors in Nervous System Disorders: From Function to
Therapeutic Perspectives.
AB - BACKGROUND: The alpha7 nicotinic receptor consists of identical subunits and is
one of the most abundant acetylcholine receptors in the mammalian central nervous
system. However its expression is also found in the peripheral nervous system as
well as in the immune system and various peripheral tissues. Nicotinic Receptors:
They are involved in the regulation of several activities ranging from excitatory
neurotransmission, the modulation of the release of several neurotransmitters,
regulation of neurite outgrowth, and even neuronal survival/death. Its expression
is found in brain areas that underlie learning and memory, suggesting their
involvement in regulating cognitive functions. The alpha7-nicotinic receptor has
a strategic role during development in regulating molecular pathways activated
during neurogenesis. Because of its pleiotropic effects, receptor dysfunction or
dysregulated expression is found in pathophysiological conditions of the nervous
system including neurodegenerative diseases and neurodevelopmental disorders.
CONCLUSION: Here we review the physiological and pathological roles of alpha-7
nicotinic receptor in different nervous system disorders and the current
therapeutic strategies developed to target selectively this receptor for
potentiating or reducing its functions.
PMID- 27488346
TI - A case of acute onset postoperative gas gangrene caused by Clostridium
perfringens.
AB - BACKGROUND: Gas gangrene is a necrotic infection of soft tissue associated with
high mortality rates. We report a case of postoperative gas gangrene with very
acute onset and rapid progression of symptoms. To our knowledge, this case is the
most acute onset of postoperative gas gangrene ever reported. CASE PRESENTATION:
A 65-year-old Japanese female patient developed a shock state 16 h after radical
cystectomy with ileal conduit reconstruction. Two days after the operation, she
was transferred to the intensive care unit because of deterioration in her
respiratory and circulatory condition. Soon after moving her to the ICU, a
subcutaneous hemorrhage-like skin rash appeared and extended rapidly over her
left side. Blood tests performed on admission to the ICU indicated severe
metabolic acidosis, liver and renal dysfunction, and signs of disseminated
intravascular coagulation. Suspecting necrotizing fasciitis or gas gangrene, we
performed emergency fasciotomy. Subsequently, multidisciplinary treatment,
including empirical therapy using multiple antibiotics, mechanical ventilation,
hyperbaric oxygen therapy, polymyxin B-immobilized fiber column direct
hemoperfusion, and continuous hemodiafiltration, was commenced. Culture of the
debris from a wound abscess removed by emergency fasciotomy detected the presence
of Clostridium perfringens. We hypothesized that the source of infection in this
case may have been the ileum used for bladder reconstruction. Although the
initial treatment prevented further clinical deterioration, she developed
secondary infection from the 3rd week onward, due to infection with multiple
pathogenic bacteria. Despite prompt diagnosis and intensive therapy, the patient
died 38 days after the operation. CONCLUSION: Although the patient did not have
any specific risk factors for postsurgical infection, she developed a shock state
only 16 h after surgery due to gas gangrene. Our experience highlights the fact
that physicians should be aware that any patient could possibly develop gas
gangrene postoperatively.
PMID- 27488347
TI - A Neuroscience-Based Nomenclature (NbN) for Psychotropic Agents.
PMID- 27488348
TI - Virtual Breast Quasi-static Elastography (VBQE).
AB - Viscoelasticity Imaging (VEI) has been proposed to measure relaxation time
constants for characterization of in vivo breast lesions. In this technique, an
external compression force on the tissue being imaged is maintained for a fixed
period of time to induce strain creep. A sequence of ultrasound echo signals is
then utilized to generate time-resolved strain measurements. Relaxation time
constants can be obtained by fitting local time-resolved strain measurements to a
viscoelastic tissue model (e.g., a modified Kevin-Voigt model). In this study,
our primary objective is to quantitatively evaluate the contrast transfer
efficiency (CTE) of VEI, which contains useful information regarding image
interpretations. Using an open-source simulator for virtual breast quasi-static
elastography (VBQE), we conducted a case study of contrast transfer efficiency of
VEI. In multiple three-dimensional (3D) numerical breast phantoms containing
various degrees of heterogeneity, finite element (FE) simulations in conjunction
with quasi-linear viscoelastic constitutive tissue models were performed to mimic
data acquisition of VEI under freehand scanning. Our results suggested that there
were losses in CTE, and the losses could be as high as -18 dB. FE results also
qualitatively corroborated clinical observations, for example, artifacts around
tissue interfaces.
PMID- 27488349
TI - A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible
for a novel form of X-linked sideroblastic anemia.
AB - The congenital sideroblastic anemias (CSAs) are a heterogeneous group of
inherited blood disorders characterized by pathological mitochondrial iron
deposition in erythroid precursors. Each known cause has been attributed to a
mutation in a protein associated with heme biosynthesis, iron-sulfur cluster
biogenesis, mitochondrial translation, or a component of the mitochondrial
respiratory chain. Here, we describe a recurring mutation, c.276_278del,
p.F93del, in NDUFB11, a mitochondrial respiratory complex I-associated protein
encoded on the X chromosome, in 5 males with a variably syndromic, normocytic
CSA. The p.F93del mutation results in respiratory insufficiency and loss of
complex I stability and activity in patient-derived fibroblasts. Targeted
introduction of this allele into K562 erythroleukemia cells results in a
proliferation defect with minimal effect on erythroid differentiation potential,
suggesting the mechanism of anemia in this disorder.
PMID- 27488350
TI - Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg
reconstitution and stabilizing Foxp3 expression.
AB - Reestablishment of competent regulatory pathways has emerged as a strategy to
reduce the severity of graft-versus-host disease (GVHD), and recalibrate the
effector and regulatory arms of the immune system. However, clinically feasible,
cost-effective strategies that do not require extensive ex vivo cellular
manipulation have remained elusive. In the current study, we demonstrate that
inhibition of the interleukin-27p28 (IL-27p28) signaling pathway through antibody
blockade or genetic ablation prevented lethal GVHD in multiple murine transplant
models. Moreover, protection from GVHD was attributable to augmented global
reconstitution of CD4+ natural regulatory T cells (nTregs), CD4+ induced Tregs
(iTregs), and CD8+ iTregs, and was more potent than temporally concordant
blockade of IL-6 signaling. Inhibition of IL-27p28 also enhanced the suppressive
capacity of adoptively transferred CD4+ nTregs by increasing the stability of
Foxp3 expression. Notably, blockade of IL-27p28 signaling reduced T-cell-derived
IL-10 production in conventional T cells; however, there was no corresponding
effect in CD4+ or CD8+ Tregs, indicating that IL-27 inhibition had differential
effects on IL-10 production and preserved a mechanistic pathway by which Tregs
are known to suppress GVHD. Targeting of IL-27 therefore represents a novel
strategy for the in vivo expansion of Tregs and subsequent prevention of GVHD
without the requirement for ex vivo cellular manipulation, and provides
additional support for the critical proinflammatory role that members of the IL-6
and IL-12 cytokine families play in GVHD biology.
PMID- 27488352
TI - Carbon-Coated Co(3+)-Rich Cobalt Selenide Derived from ZIF-67 for Efficient
Electrochemical Water Oxidation.
AB - Oxygen evolution reaction (OER) electrocatalysts are confronted with challenges
such as sluggish kinetics, low conductivity, and instability, restricting the
development of water splitting. In this study, we report an efficient Co(3+)-rich
cobalt selenide (Co0.85Se) nanoparticles coated with carbon shell as OER
electrocatalyst, which are derived from zeolitic imidazolate framework (ZIF-67)
precursor. It is proposed that the organic ligands in the ZIF-67 can effectively
enrich and stabilize the Co(3+) ions in the inorganic-organic frameworks and
subsequent carbon-coated nanoparticles. In alkaline media, the catalyst exhibits
excellent OER performances, which are attributed to its abundant active sites,
high conductivity, and superior kinetics.
PMID- 27488351
TI - Sex-dependent adaptive changes in serotonin-1A autoreceptor function and anxiety
in Deaf1-deficient mice.
AB - The C (-1019) G rs6295 promoter polymorphism of the serotonin-1A (5-HT1A)
receptor gene is associated with major depression in several but not all studies,
suggesting that compensatory mechanisms mediate resilience. The rs6295 risk
allele prevents binding of the repressor Deaf1 increasing 5-HT1A receptor gene
transcription, and the Deaf1-/- mouse model shows an increase in 5-HT1A
autoreceptor expression. In this study, Deaf1-/- mice bred on a mixed C57BL6
BALB/c background were compared to wild-type littermates for 5-HT1A autoreceptor
function and behavior in males and females. Despite a sustained increase in 5
HT1A autoreceptor binding levels, the amplitude of the 5-HT1A autoreceptor
mediated current in 5-HT neurons was unaltered in Deaf1-/- mice, suggesting
compensatory changes in receptor function. Consistent with increased 5-HT1A
autoreceptor function in vivo, hypothermia induced by the 5-HT1A agonist DPAT was
augmented in early generation male but not female Deaf1-/- mice, but was reduced
with succeeding generations. Loss of Deaf1 resulted in a mild anxiety phenotype
that was sex-and test-dependent, with no change in depression-like behavior. Male
Deaf1 knockout mice displayed anxiety-like behavior in the open field and light
dark tests, while female Deaf1-/- mice showed increased anxiety only in the
elevated plus maze. These data show that altered 5-HT1A autoreceptor regulation
in male Deaf1-/- mice can be compensated for by generational adaptation of
receptor response that may help to normalize behavior. The sex dependence of
Deaf1 function in mice is consistent with a greater role for 5-HT1A autoreceptors
in sensitivity to depression in men.
PMID- 27488353
TI - Moderator's view: Salt, cardiovascular risk, observational research and
recommendations for clinical practice.
AB - In observational studies, blood pressure (BP), cholesterol and nutritional status
biomarkers, including sodium intake, coherently show a J- or U-shaped
relationship with health outcomes. Yet these data may reflect a stable sodium
intake or a reduced intake due to comorbidities or intercurrent disease, or an
intentional decrease in salt intake. Adjusting for comorbidities and risk factors
may fail to eliminate confounding. For cholesterol and BP, we base our
recommendations for prevention and treatment on interventional (experimental)
studies. For sodium, we lack the perfect large-scale trial we would need, but
substantial circumstantial information derived from interventional studies cannot
be ignored. The objection that modelling the risk of salt excess for
cardiovascular disease events based on the effect of salt intake on BP is
unjustified fails to consider a recent meta-analysis showing that, independently
of the intervention applied, intensive BP-lowering treatment (average BP 133/76
mmHg), compared with the less intensive treatment (140/81 mmHg), is associated
with a 14% risk reduction for major cardiovascular events. In this knowledge
context, inertia, i.e. awaiting the 'mother trial', is not justified. While
recognizing that this trial may still be needed and that actual data, rather than
modelled data, are the ideal solution, for now, the World Health Organization
recommendation of reducing salt intake to <2 g/day of sodium (5 g/day of salt) in
adults stands.
PMID- 27488354
TI - Con: Reducing salt intake at the population level: is it really a public health
priority?
AB - Scientific evidence to support the recommended salt intake of < 5.8 g/day is
virtually non-existingent. There are no randomized controlled trials (RCTs) to
investigate the effect of salt reduction (SR) below 5.8 g on health outcomes. The
effect of SR on blood pressure (BP) reaches maximal efficacy at 1 week. RCTs in
healthy individuals lasting at least 1 week show that the effect of SR on BP is
<1 mmHg, but that SR has significant side effects, including increases in renin,
aldosterone, noradrenalin, adrenalin, cholesterol and triglyceride. Still,
disregarding confounders and side effects, health authorities use BP effects
obtained in studies of pre-hypertensive and hypertensive patients to recommend SR
in the healthy population and use these biased BP effects in statistical models
indirectly to project millions of saved lives. These fantasy projections are in
contrast to real data from prospective observational population studies directly
associating salt intake with mortality, which show that salt intake <5.8 g/day is
associated with an increased mortality of ~15%. The population studies also show
that a very high salt intake >12.2 g is associated with increased mortality.
However, since <5% of populations consume such high amounts of salt, SR at the
population level should not be a public health priority. Consequently, this
policy should be abolished, not because any attempt to implement it has failed,
and not because it costs taxpayers and food consumers unnecessary billions of
dollars, but because-if implemented-it might kill people instead of saving them.
PMID- 27488355
TI - Pro: Reducing salt intake at population level: is it really a public health
priority?
AB - A reduction in salt intake reduces blood pressure, stroke and other
cardiovascular events, including chronic kidney disease, by as much as 23% (i.e.
1.25 million deaths worldwide). It is effective in both genders, any age, ethnic
group, and in high-, medium- and low-income countries. Population salt reduction
programmes are both feasible and effective (preventive imperative). Salt
reduction programmes are cost-saving in all settings (high-, middle- and low
income countries) (economic imperative). Public health policies are powerful,
rapid, equitable and cost-saving (political imperative). The important shift in
public health has not occurred without obstinate opposition from organizations
concerned primarily with the profits deriving from population high salt intake
and less with public health benefits. A key component of the denial strategy is
misinformation (with 'pseudo' controversies). In general, poor science has been
used to create uncertainty and to support inaction. This paper summarizes the
evidence in favour of a global salt reduction strategy and analyses the peddling
of well-worn myths behind the false controversies.
PMID- 27488356
TI - Priority of the genus name Clostridium Prazmowski 1880 (Approved Lists 1980) vs
Sarcina Goodsir 1842 (Approved Lists 1980) and the creation of the illegitimate
combinations Clostridium maximum (Lindner 1888) Lawson and Rainey 2016 and
Clostridium ventriculi (Goodsir 1842) Lawson and Rainey 2016 that may not be
used.
AB - In a recent publication that attempts to deal with the growing problem of taxa
being added to the genus Clostridium that are outside of Clostridium (16S rRNA)
group I, a solution is proposed that seeks to limit the genus Clostridium
Prazmowski 1880 (Approved Lists 1980) to a small number of species 'related' to
the type species, Clostridium butyricum Prazmowski 1880 (Approved Lists 1980). It
has been proposed that this genus should also include members of the genus
Sarcina Goodsir 1842 (Approved Lists 1980), Sarcinamaxima Lindner 1888 (Approved
Lists 1980) and Sarcinaventriculi Goodsir 1842 (Approved Lists 1980), the latter
being the nomenclatural type of the genus Sarcina Goodsir 1842 (Approved Lists
1980). In making proposals to treat the genus name Sarcina Goodsir 1842 (Approved
Lists 1980) as a synonym of ClostridiumPrazmowski 1880 (Approved Lists 1980),
reference is made to the wording of the International Code of Nomenclature of
Bacteria. However, while that wording is factually correct, other parts of the
Code are relevant to this issue and clearly indicate that the proposed course of
action is not sanctioned by texts that have not been directly made reference to.
Rather than avoiding confusion it has been contributed to, and it is necessary to
document where the problems lie.
PMID- 27488357
TI - Use of electronic cigarettes among secondary and high school students from a
socially disadvantaged rural area in Poland.
AB - BACKGROUND: The use of e-cigarettes has been growing and has become a significant
public health concern. Prevention of the youth access to, initiation and
continuous use of e-cigarettes with special attention to vulnerable groups is a
subject of a health debate. However, still little is known about characteristics
of the underage e-cigarette users from different geographic and socio-economic
backgrounds as well as other potential factors associated with the use of e
cigarettes, including simultaneous use with tobacco products or alcohol. The aim
of the study was to investigate the prevalence and factors associated with ever
and continued e-cigarette use among the secondary and high school students from a
socially disadvantaged rural area in Poland. METHODS: The study sample consisted
of 3552 students aged 13-19 years from Piotrkowski district. The anonymous, self
administered questionnaire adapted from the Global Youth Tobacco Survey was
implemented to collect relevant information. The uni- and multivariate logistic
regression analyses were applied to identify factors associated with ever,
current (in the previous 30 days) and continued e-cigarette use. RESULTS: Almost
22 % of the sample reported ever e-cigarettes use and 27 % of the respondents
indicated e-cigarettes use in the past month. Boys, in comparison with girls,
were more likely to report current e-cigarette use (OR = 1.7; p < 0.001). Current
e-cigarette use was strongly associated with alcohol consumption (OR = 4.3; p <
0.001), current (OR = 32.5; p < 0.001) and ever tobacco smoking (OR = 7.5; p <
0.001) as well as smoking parents (OR = 1.4; p < 0.05) and friends (OR = 4.5; p <
0.05). The use of e-cigarettes was also significantly associated with harm
perception (p < 0.001). A similar pattern was observed among ever e-cigarette
users. Male gender (OR = 1.4; p < 0.05), current tobacco smoking (OR = 3.0; p <
0.01) and lack of knowledge about a ban on smoking in the school (OR = 1.4; p <
0.05) were predictors of the continued e-cigarette use. Higher paternal education
(OR = 0.5; p < 0.001) and perception of e-cigarettes as more harmful comparing to
tobacco (OR = 0.2; p < 0.001) protected from the continued e-cigarette use.
CONCLUSIONS: E-cigarette use is widespread in the investigated population,
especially among boys, those with other risky behaviors and with smoking parents
or friends. There is a need for further research and preventive policies to
protect the youth from that exposure.
PMID- 27488358
TI - Genome-wide association mapping of soybean chlorophyll traits based on canopy
spectral reflectance and leaf extracts.
AB - BACKGROUND: Chlorophyll is a major component of chloroplasts and a better
understanding of the genetic basis of chlorophyll in soybean [Glycine max (L.)
Merr.] might contribute to improving photosynthetic capacity and yield in regions
with adverse environmental conditions. A collection of 332 diverse soybean
genotypes were grown in 2 years (2009 and 2010) and chlorophyll a (eChl_A),
chlorophyll b (eChl_B), and total chlorophyll (eChl_T) content as well as
chlorophyll a/b ratio (eChl_R) in leaf tissues were determined by extraction and
spectrometric determination. Total chlorophyll was also derived from canopy
spectral reflectance measurements using a model of wavelet transformed spectra
(tChl_T) as well as with a spectral reflectance index (iChl_T). RESULTS: A genome
wide associating mapping approach was employed using 31,253 single nucleotide
polymorphisms (SNPs) to identify loci associated with the extract based eChl_A,
eChl_B, eChl_R and eChl_T measurements and the two canopy spectral reflectance
based methods (tChl_T and iChl_T). A total of 23 (14 loci), 15 (7 loci) and 14
SNPs (10 loci) showed significant association with eChl_A, eChl_B and eChl_R
respectively. A total of 52 unique SNPs were significantly associated with total
chlorophyll content based on at least one of the three approaches (eChl_T, tChl_T
and iChl_T) and likely tagged 27 putative loci for total chlorophyll content,
four of which were indicated by all three approaches. CONCLUSIONS: Results
presented here show that markers for chlorophyll traits can be identified in
soybean using both extract-based and canopy spectral reflectance-based
phenotypes, and confirm that high-throughput phenotyping-amenable canopy spectral
reflectance measurements can be used for association mapping.
PMID- 27488359
TI - Effect of gamma-carboxylase inhibition on serum osteocalcin may be partially
protective against developing diabetic cardiomyopathy in type 2 diabetic rats.
AB - AIMS: To investigate the possible protective effect of elevated undercarboxylated
osteocalcin on diabetic cardiomyopathy mechanisms and risk factors. METHODS: In
all, 32 male rats were divided into four groups: control, diabetic, diabetic
warfarin and normal warfarin-treated groups. Isolated heart functions were
assessed; fasting serum insulin, glucose and glycosylated haemoglobin,
homeostasis model assessment insulin resistance and lipid profile were
investigated. Serum undercarboxylated osteocalcin and adiponectin were also
measured. In cardiac tissue, malondialdehyde content, acyl-CoA dehydrogenase gene
expression, Bax/Bcl2 ratio, sarcoendoplasmic reticulum calcium ATPase and
osteocalcin receptor (G protein-coupled receptor family C group 6 member A) genes
expression were investigated. RESULTS: Prophylactic elevation of
undercarboxylated osteocalcin was accompanied by improved insulin sensitivity and
lipid profile, increased serum adiponectin, upregulated myocardial osteocalcin
receptor with preserved left ventricular function, decreased cardiac
malondialdehyde content, acyl-CoA dehydrogenase and Bax/Bcl2 ratio. CONCLUSION:
Undercarboxylated osteocalcin was suggested to have protective effects against
diabetic cardiomyopathy, possibly through direct action on upregulated G protein
coupled receptor family C group 6 member A and indirectly via adiponectin. These
effects may be mediated through antagonizing oxidative stress and apoptosis.
PMID- 27488360
TI - Fasting glucose levels, incident diabetes, subclinical atherosclerosis and
cardiovascular events in apparently healthy adults: A 12-year longitudinal study.
AB - We aimed to study the association between fasting plasma glucose, diabetes
incidence and cardiovascular burden after 10-12 years. We evaluated diabetes and
cardiovascular events incidences, carotid intima-media thickness and coronary
artery calcium scores in ELSA-Brasil (the Brazilian Longitudinal Study of Adult
Health) baseline (2008-2010) of 1536 adults without diabetes in 1998. We used
regression models to estimate association with carotid intima-media thickness (in
mm), coronary artery calcium scores (in Agatston points) and cardiovascular
events according to fasting plasma glucose in 1998. Adjusted diabetes incidence
rate was 9.8/1000 person-years (95% confidence interval: 7.7-13.6/1000 person
years). Incident diabetes was positively associated with higher fasting plasma
glucose. Fasting plasma glucose levels 110-125 mg/dL were associated with higher
carotid intima-media thickness (beta = 0.028; 95% confidence interval: 0.003
0.053). Excluding those with incident diabetes, there was a borderline
association between higher carotid intima-media thickness and fasting plasma
glucose 110-125 mg/dL (beta = 0.030; 95% confidence interval: -0.005 to 0.065).
Incident diabetes was associated with higher carotid intima-media thickness (beta
= 0.034; 95% confidence interval: 0.015-0.053), coronary artery calcium scores
?400 (odds ratio = 2.84; 95% confidence interval: 1.17-6.91) and the combined
outcome of a coronary artery calcium scores ?400 or incident cardiovascular event
(odds ratio = 3.50; 95% confidence interval: 1.60-7.65). In conclusion, fasting
plasma glucose in 1998 and incident diabetes were associated with higher
cardiovascular burden.
PMID- 27488362
TI - Impact of timing from blood sampling to pharmacodynamic assessment on measures of
platelet reactivity in patients treated with P2Y12 receptor inhibitors.
AB - Several platelet function tests (PFT) are available to assess the pharmacodynamic
(PD) effects of P2Y12 inhibitors. However, there are technical variances between
PFT, and P2Y12 inhibitors differ in pharmacological properties. Manufactures of
PFT recommend a time-frame within which assessments needs to be executed.
However, if the timing from blood sampling to processing affects PD results is
unknown. We conducted a prospective study assessing the impact of timing from
blood sampling to processing on PD measures using three different PFT. We studied
60 aspirin-treated patients with coronary artery disease (CAD) on maintenance
P2Y12 inhibiting therapy [clopidogrel 75 mg/day (n=20), prasugrel 10 mg/day
(n=20) and ticagrelor 90 mg bid (n=20)]. PD assessments (trough levels) were
performed by VerifyNow P2Y12 (VN), light transmittance aggregometry (LTA) and
vasodilator-stimulated phosphoprotein (VASP) at 30 minutes, 2 and 4 hours post
sampling; VASP was also performed at 24 hours. P2Y12 reaction units (PRU) by VN
significantly decreased over time with all P2Y12 inhibitors (clopidogrel p<0.001;
prasugrel p=0.016; ticagrelor p<0.001). PRU at 30 minutes and 2 hours were
similar, but decreased at 4 hours. LTA showed consistent findings with VN.
Conversely, PD measures as assessed by VASP were stable over time (p>0.1 for all
P2Y12 inhibitors). In conclusion, in CAD patients on maintenance therapy with
P2Y12 inhibitors, timing from blood sampling to processing significantly
influences PD measures as assessed by VN and LTA, but not by VASP.
PMID- 27488361
TI - Learning from doing: the case for combining normalisation process theory and
participatory learning and action research methodology for primary healthcare
implementation research.
AB - BACKGROUND: The implementation of research findings is not a straightforward
matter. There are substantive and recognised gaps in the process of translating
research findings into practice and policy. In order to overcome some of these
translational difficulties, a number of strategies have been proposed for
researchers. These include greater use of theoretical approaches in research
focused on implementation, and use of a wider range of research methods
appropriate to policy questions and the wider social context in which they are
placed. However, questions remain about how to combine theory and method in
implementation research. In this paper, we respond to these proposals.
DISCUSSION: Focussing on a contemporary social theory, Normalisation Process
Theory, and a participatory research methodology, Participatory Learning and
Action, we discuss the potential of their combined use for implementation
research. We note ways in which Normalisation Process Theory and Participatory
Learning and Action are congruent and may therefore be used as heuristic devices
to explore, better understand and support implementation. We also provide
examples of their use in our own research programme about community involvement
in primary healthcare. CONCLUSIONS: Normalisation Process Theory alone has, to
date, offered useful explanations for the success or otherwise of implementation
projects post-implementation. We argue that Normalisation Process Theory can also
be used to prospectively support implementation journeys. Furthermore,
Normalisation Process Theory and Participatory Learning and Action can be used
together so that interventions to support implementation work are devised and
enacted with the expertise of key stakeholders. We propose that the specific
combination of this theory and methodology possesses the potential, because of
their combined heuristic force, to offer a more effective means of supporting
implementation projects than either one might do on its own, and of providing
deeper understandings of implementation contexts, rather than merely describing
change.
PMID- 27488364
TI - Erratum to: Classical swine fever virus NS5A protein changed inflammatory
cytokine secretion in porcine alveolar macrophages by inhibiting the NF-kappaB
signaling pathway.
PMID- 27488363
TI - Intestinal development of bovine foetuses during gestation is affected by foetal
sex and maternal nutrition.
AB - We aimed to evaluate the effects of maternal nutrition (MN) and foetal sex on the
intestinal development of bovine foetuses throughout different days of gestation
(DG). Forty-four multiparous, dry Holstein * Gyr cows with average initial body
weight of 480 +/- 10 kg were fed the same diet of either restricted feeding at
1.15% of body weight (CO, n = 24) or fed ad libitum (overnourished, ON, n = 20).
Six cows from CO group and five cows from ON group were slaughtered at 139, 199,
241 and 268 DG, and foetuses were necropsied to evaluate the intestinal
development. The mass, length and density of foetal intestines were not affected
by MN (p >= 0.260). An interaction between MN and DG was observed for the villi
length of jejunum (p = 0.006) and ileum (p < 0.001). Villi length of jejunum and
ileum was higher (p < 0.10) in foetuses from ON-fed cows than in foetuses from CO
fed cows at 139 DG. However, at 199 DG, the villi length of jejunum and ileum of
foetuses from CO-fed cows was higher than in foetuses from ON-fed cows. Despite
these differences, MN did not affect the villi length of jejunum and ileum at 268
DG (p > 0.10). Female foetuses had greater small intestine mass (p = 0.093),
large intestine mass (p = 0.022), small intestine mass in proportion to body mass
(p = 0.017) and large intestine mass in proportion to body mass (p < 0.001) than
male foetuses. Female foetuses had also longer small intestine (p = 0.077) and
greater small intestine density (p = 0.021) and villi length of jejunum (p =
0.001) and ileum (p = 0.010) than males. We conclude that MN affects the pathway
for the development of foetal villi length throughout the gestation in bovine
foetuses without changing the final villi length. Female foetuses had higher
intestinal mass, density and villi length than males during the foetal phase in
bovines.
PMID- 27488365
TI - Effect of medication timing on anticoagulation stability in users of warfarin
(the INRange RCT): study protocol for a randomized controlled trial.
AB - BACKGROUND: Warfarin is an oral anticoagulant medication that disrupts the
liver's production of clotting factors. While this medication is highly effective
for the prevention of thromboembolic events, it also has a narrow therapeutic
range and a vulnerability to interactions with other drugs and vitamin K
containing foods. Warfarin is commonly ingested at dinnertime, the same time of
day that dietary vitamin K consumption (found largely in green leafy vegetables)
is most variable. While the long half-life of warfarin might make this
irrelevant, the ultra short half-life of vitamin K and the possibility of a
hepatic first-pass effect for warfarin make it worth evaluating whether morning
ingestion of warfarin, when vitamin K levels are consistently low, leads to
greater stability of its anticoagulant effect. An examination of the timing of
administration on the effectiveness of warfarin has never before been conducted.
METHODS/DESIGN: This is a 7-month Prospective Randomized Open Blinded End-point
(PROBE) study in which established evening warfarin users (primary care managed
Canadian outpatients in the provinces of British Columbia and Alberta) will be
randomized to either switch to morning ingestion of warfarin (the intervention)
or to continue with evening use (the control). The primary outcome is the percent
change in the proportion of time spent outside the therapeutic range of the
international normalized ratio (INR) blood test. Secondary outcomes include
change in proportion of time spent within the therapeutic INR range (TTR),
percentage of patients with TTR >75 %, percentage of patients with TTR <60 %, and
major warfarin-related cardiovascular events (including all-cause mortality,
hospitalization for stroke, hospitalization for GI bleeding, and deep venous
thrombosis/pulmonary embolism). We will also compare whether day-to-day
variability in the consumption of high vitamin K-containing foods at baseline
affects the baseline TTR in this cohort of evening warfarin users. DISCUSSION:
This study addresses whether the timing of warfarin ingestion influences the
stability of its anticoagulant effect. Should morning ingestion prove superior,
the safety and effectiveness of this medication, and hence the prevention of
stroke, pulmonary embolus, and major hemorrhage, could potentially be improved
with no added cost or inconvenience to the patient. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT02376803 . Registered on 25 February 2015.
PMID- 27488366
TI - Allogeneic anorectal transplantation in rats: technical considerations and
preliminary results.
AB - Fecal incontinence is a challenging condition with numerous available treatment
modalities. Success rates vary across these modalities, and permanent colostomy
is often indicated when they fail. For these cases, a novel potential therapeutic
strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis
to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum
was retrieved with a vascular pedicle containing the aorta in continuity with the
inferior mesenteric artery and portal vein in continuity with the inferior
mesenteric vein. In the recipient, the native anorectal segment was removed and
the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses
and end-to-end colorectal anastomosis. Recipients were sacrificed at the
experimental endpoint on postoperative day 30. Surviving animals resumed normal
body weight gain and clinical performance within 5 days of surgery. Isografts and
42.9% of allografts achieved normal clinical evolution up to the experimental
endpoint. In 57.1% of allografts, signs of immunological rejection (abdominal
distention, diarrhea, and anal mucosa inflammation) were observed three weeks
after transplantation. Histology revealed moderate to severe rejection in
allografts and no signs of rejection in isografts. We describe a feasible model
of ATx in rats, which may allow further physiological and immunologic studies.
PMID- 27488367
TI - ERPs in an oddball task under vection-inducing visual stimulation.
AB - The neural mechanisms underlying the vection illusion are not fully understood. A
few studies have analyzed visually evoked potentials or event-related potentials
(ERPs) when participants were exposed to vection-inducing stimulation. However,
none of them tested how such stimulation influences the brain activity during
performance of the simultaneous visual task. In the present study, ERPs were
recorded while subjects (N = 19) performed a discrimination oddball task. Two
stimuli (O or X) were presented on the background of central and peripheral
visual fields consisting of altered black and white vertical stripes that were
stationary or moving horizontally. Three different combinations of these fields
were created: (1) both center and periphery stationary (control condition), (2)
both center and periphery moving, (3) center stationary and periphery moving.
Mean reaction times to targets were shortest in the control condition. The
amplitudes of P1 and N2 at occipital locations, and the amplitude of P3 at
frontal, central, and parietal locations, were attenuated, and the P3 exhibited
longer peak latency when both central and peripheral visual fields were moving.
These potentials reflect initial sensory processing and the degree of attention
required for processing visual stimuli and performing the task. Our findings
suggest that the integration of central and peripheral moving visual fields
enhances the vection illusion and slows down reaction times to targets in the
oddball task and disrupts the magnitude of electrophysiological responses to
targets.
PMID- 27488368
TI - Behavioral and Nondirective Guided Self-Help for Parents of Children with
Externalizing Behavior: Mediating Mechanisms in a Head-To-Head Comparison.
AB - Parent training (PT) delivered as a guided self-help intervention may be a cost-
and time-effective intervention in the treatment of children with externalizing
disorders. In face-to-face PT, parenting strategies have repeatedly been
identified as mediating mechanisms for the decrease of children's problem
behavior. Few studies have examined possible mediating effects in guided self
help interventions for parents. The present study aimed to investigate possible
mediating variables of a behaviorally oriented guided self-help program for
parents of children with externalizing problems compared to a nondirective
intervention in a clinical sample. A sample of 110 parents of children with
externalizing disorders (80 % boys) were randomized to either a behaviorally
oriented or a nondirective guided self-help program. Four putative mediating
variables were examined simultaneously in a multiple mediation model using
structural equation modelling. The outcomes were child symptoms of ADHD and ODD
as well as child externalizing problems, assessed at posttreatment. Analyses
showed a significant indirect effect for dysfunctional parental attributions in
favor of the group receiving the behavioral program, and significant effects of
the behavioral program on positive and negative parenting and parental self
efficacy, compared to the nondirective intervention. Our results indicate that a
decrease of dysfunctional parental attributions leads to a decrease of child
externalizing problems when parents take part in a behaviorally oriented guided
self-help program. However, none of the putative mediating variables could
explain the decrease in child externalizing behavior problems in the nondirective
group. A change in dysfunctional parental attributions should be considered as a
possible mediator in the context of PT.
PMID- 27488370
TI - Treatment Effects for Dysphagia in Adults with Multiple Sclerosis: A Systematic
Review.
AB - Dysphagia or swallowing difficulties have been reported to be a concern in adults
with multiple sclerosis (MS). This problem can result in several complications
including aspiration pneumonia, reduced quality of life and an increase in
mortality rate. No previous systematic reviews on treatment effects for dysphagia
in MS have been published. The main objective of this study is to summarise and
qualitatively analyse published studies on treatment effects for dysphagia in MS.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines
were applied to conduct a systematic search of seven databases, using relevant
key words, and subsequent analysis of the identified studies. The studies were
required to meet all three inclusion criteria of including a statement on
intention to treat, or measure the effects of treatment for dysphagia in adults
with MS and data on treatment outcomes for at least one adult diagnosed with MS.
Retained studies were evaluated by two independent reviewers using a critical
appraisal tool. This study has not been registered. A total of 563 studies were
identified from the database searches. After screening and assessment of full
articles for eligibility, five studies were included in the review. Three
examined electrical stimulation and two examined the use of botulinum toxin. One
study testing electrical stimulation was a randomised controlled trial, two were
well-designed case series and two were case series lacking experimental control.
All studies reported some positive effects on dysphagia; however, treatments that
involved the use of electrical stimulation showed larger effect sizes. There is a
paucity of evidence to guide treatment of dysphagia in MS, with only electrical
stimulation and botulinum toxin treatment represented in the literature search
conducted here. While both treatments show initial promise for reducing the
swallowing impairment, they require further research using well-controlled
experimental designs to determine their clinical applicability and long-term
treatment effects for dysphagia across different types and severity of MS.
PMID- 27488369
TI - Born in Bradford's Better Start: an experimental birth cohort study to evaluate
the impact of early life interventions.
AB - BACKGROUND: Early interventions are recognised as key to improving life chances
for children and reducing inequalities in health and well-being, however there is
a paucity of high quality research into the effectiveness of interventions to
address childhood health and development outcomes. Planning and implementing
standalone RCTs for multiple, individual interventions would be slow, cumbersome
and expensive. This paper describes the protocol for an innovative experimental
birth cohort: Born in Bradford's Better Start (BiBBS) that will simultaneously
evaluate the impact of multiple early life interventions using efficient study
designs. Better Start Bradford (BSB) has been allocated L49 million from the Big
Lottery Fund to implement 22 interventions to improve outcomes for children aged
0-3 in three key areas: social and emotional development; communication and
language development; and nutrition and obesity. The interventions will be
implemented in three deprived and ethnically diverse inner city areas of
Bradford. METHOD: The BiBBS study aims to recruit 5000 babies, their mothers and
their mothers' partners over 5 years from January 2016-December 2020. Demographic
and socioeconomic information, physical and mental health, lifestyle factors and
biological samples will be collected during pregnancy. Parents and children will
be linked to their routine health and local authority (including education) data
throughout the children's lives. Their participation in BSB interventions will
also be tracked. BiBBS will test interventions using the Trials within Cohorts
(TwiCs) approach and other quasi-experimental designs where TwiCs are neither
feasible nor ethical, to evaluate these early life interventions. The effects of
single interventions, and the cumulative effects of stacked (multiple)
interventions on health and social outcomes during the critical early years will
be measured. DISCUSSION: The focus of the BiBBS cohort is on intervention impact
rather than observation. As far as we are aware BiBBS is the world's first such
experimental birth cohort study. While some risk factors for adverse health and
social outcomes are increasingly well described, the solutions to tackling them
remain elusive. The novel design of BiBBS can contribute much needed evidence to
inform policy makers and practitioners about effective approaches to improve
health and well-being for future generations.
PMID- 27488371
TI - Comparison of detection methods and follow-up study on the tyrosine kinase
inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion
rearrangement.
AB - BACKGROUND: The screening of ROS proto-oncogene 1, receptor tyrosine kinase(ROS1)
fusion rearrangement might be potentially beneficial for an effective therapy
against non-small cell lung cancer (NSCLC). However, the three main ROS1
rearrangement detection methods have limitations, and no routine protocol for the
detection of ROS1 rearrangement in NSCLC is available. In this study, our aims
were to compare immunohistochemistry (IHC), fluorescent in situ hybridization
(FISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in their
ability to detect ROS1 rearrangement in NSCLC, and discuss the clinical
characteristics and histopathology of the patients with ROS1 rearrangement.
Moreover, the effects of tyrosine kinase inhibitors (TKIs) therapy on the
patients with ROS1 rearrangement and advanced stage disease (III b-IV) were
investigated. METHODS: Patients with a previously diagnosed NSCLC were recruited
in this study from November 2013 to October 2015. IHC was performed using the
D4D6 monoclonal antibody (mAb) in an automatic IHC instrument, while FISH and qRT
PCR were carried out to confirm the IHC results. FISH and qRT-PCR positive cases
underwent direct sequencing. After detection, patients with advanced ROS1
rearranged NSCLC had received TKI therapy. RESULTS: Two hundred and thirty-eight
patients were included in this study. ROS1 rearrangement was detected in 10
patients. The concordant rate of FISH and qRT-PCR results was 100 %, while in the
FISH and IHC results high congruence was present when IHC showed a diffusely
(>=60 % tumor cells) 2-3+ cytoplasmic reactivity pattern. Patients harboring ROS1
rearrangement were mostly young (8/10), females (7/10) and non-smokers (7/10)
with adenocarcinoma (10/10) and acinar pattern. Most of their tumor were in
intermediate grade (6/8). Among these 10 patients, three of them in stage IV with
ROS1 rearrangement gained benefits from ROS1 TKI therapy. CONCLUSIONS: IHC, FISH
and qRT-PCR can reliably detect ROS1 rearrangement in NSCLC, while IHC can be
used as a preliminary screening tool. These results supported the efficacy of
ROS1 TKI therapy in treating advanced NSCLC patients with ROS1 rearrangement.
PMID- 27488372
TI - LPS-matured CD11c+ bone marrow-derived dendritic cells can initiate autoimmune
pathology with minimal injection site inflammation.
AB - The pathogenesis of human autoimmune disorders is incompletely understood. This
has led to the development of numerous murine models in which the pathogenesis of
autoimmunity can be probed and the efficacy of novel therapies can be tested. One
of the most widely-used murine models of autoimmunity is experimental autoimmune
encephalomyelitis (EAE). To induce autoimmune pathology, mice are often immunized
with an autoantigen alongside an adjuvant, typically complete Freund's adjuvant
(CFA). Unfortunately, CFA causes significant inflammation at the site of
administration. Despite the well-recognized complication of injection site
inflammation, CFA with autoantigen immunization is widely used to induce central
nervous system autoimmunity. We performed a literature review which allowed us to
estimate that over 10,000 mice were immunized with CFA in published EAE studies
in 2013. In this study, we demonstrated that subcutaneously administered myelin
basic protein (MBP)-pulsed CD11c+ bone marrow-derived dendritic cells (BMDC) were
as effective at inducing EAE as subcutaneously administered MBP plus CFA.
Importantly, we also discovered that the CD11c+ BMDC caused significantly less
injection site inflammation than MBP plus CFA immunization. This study
demonstrated that the use of CD11c+ BMDC can enable the development of
autopathogenic T-cells to be studied in vivo without the unwanted side-effects of
long-lasting injection site inflammation. This model represents a significant
refinement to existing EAE models and may lead to the improvement of the welfare
of experimental mice used to study the development of autoimmunity in vivo.
PMID- 27488373
TI - Hyperthermia phased arrays pre-treatment evaluation.
AB - PURPOSE: In the hyperthermia treatment of deep-seated tumours by a phased array
of radiofrequency (RF) antennas, heatability will be investigated in terms of
power-to-tumour and other figures-of-merit of hyperthermia treatments to be
optimised. The assumption is that each source is individually constrained to not
exceed a maximal nominal power. The nominal power may differ from a source to
another as a physical limit or an operative modality. METHOD: Under such
constraint, new procedures for the maximisation of (i) power-to-tumour, (ii)
heating efficiency and, in general, (iii) power ratios as tumour-heating
selectivity are proposed. (iv) The problem whether a tumour is equally heatable
after turning off some antennas is addressed as array thinning. CASE STUDY: An
array of eight dipoles arranged on two lines around a head/neck is introduced to
perform a numerical analysis. The achievable power-to-tumour according to the new
optimizations and other performance indices adopted from the literature is tested
against values of power that can be found to be sufficient for heating tumours to
clinical temperatures. New solutions to data rendering in hyperthermia heating
are proposed.
PMID- 27488374
TI - Nodal signalling in Xenopus: the role of Xnr5 in left/right asymmetry and heart
development.
AB - Nodal class TGF-beta signalling molecules play essential roles in establishing
the vertebrate body plan. In all vertebrates, nodal family members have specific
waves of expression required for tissue specification and axis formation. In
Xenopus laevis, six nodal genes are expressed before gastrulation, raising the
question of whether they have specific roles or act redundantly with each other.
Here, we examine the role of Xnr5. We find it acts at the late blastula stage as
a mesoderm inducer and repressor of ectodermal gene expression, a role it shares
with Vg1. However, unlike Vg1, Xnr5 depletion reduces the expression of the nodal
family member xnr1 at the gastrula stage. It is also required for left/right
laterality by controlling the expression of the laterality genes xnr1, antivin
(lefty) and pitx2 at the tailbud stage. In Xnr5-depleted embryos, the heart field
is established normally, but symmetrical reduction in Xnr5 levels causes a
severely stunted midline heart, first evidenced by a reduction in cardiac
troponin mRNA levels, while left-sided reduction leads to randomization of the
left/right axis. This work identifies Xnr5 as the earliest step in the signalling
pathway establishing normal heart laterality in Xenopus.
PMID- 27488375
TI - An invertebrate-specific miRNA targeted the ancient cholinergic neuroendocrine
system of oyster.
AB - Acetylcholine (ACh) is the main neurotransmitter in the cholinergic
neuroendocrine system and plays an indispensable role in modulating diverse
immune responses. As important transporters in choline uptake, choline
transporter-like proteins (CTLs) can control ACh synthesis and release indirectly
in multiple organisms. In this study, cgi-miR-2d, an invertebrate-specific miRNA
in oyster Crassostrea gigas, is proved to repress the synthesis/release of ACh by
targeting CgCTL1 and choline uptake in haemocytes during the early stage of
pathogen infection. In short, an opposite expression pattern between CgCTL1 and
cgi-miR-2d is observed during Vibrio splendidus infection, accompanied by changes
in haemolymph ACh. In addition, the expression level of CgCTL1 is found to be
significantly repressed after cgi-miR-2d overexpression in vivo, while both
haemocyte choline and haemolymph ACh are also decreased simultaneously, similar
to the finding in CgCTL1 knock-down assay. As a result, the expression of two
tumour necrosis factor-like proteins and the bacteriostatic activity of oyster
haemocytes are found to be altered significantly by either gain-of-function cgi
miR-2d or knock-down of CgCTL1. To our knowledge, this is the first miRNA
identified in invertebrates that can target the ancient cholinergic system and
augment immune response during infection.
PMID- 27488377
TI - Elevated extension of longevity by cyclically heat stressing a set of recombinant
inbred lines of Drosophila melanogaster throughout their adult life.
AB - An extremely high (about 100 %) increase in longevity is reported for a subset of
recombinant inbred lines (RILs) of Drosophila melanogaster subjected to a cyclic
heat stress throughout the adult life. Previous work showed that both longevity
and heat sensitivity highly differed among RILs. The novel heat stress treatment
used in this study consisted of 5 min at 38 degrees C applicated approximately
every 125 min throughout the adult life starting at the age of 2 days. In spite
of the exceptionally high increase in longevity in a set of RILs, the same heat
stress treatment reduced rather than increased longevity in other RILs,
suggesting that heat-induced hormesis is dependent on the genotype and/or the
genetic background. Further, one quantitative trait locus (QTL) was identified
for heat-induced hormesis on chromosome 2 (bands 28A1-34D2) in one RIL panel (RIL
D48) but it was not significant in its reciprocal panel (RIL-SH2). The level of
heat-induced hormesis showed a sexual dimorphism, with a higher number of lines
exhibiting higher hormesis effects in males than in females. The new heat stress
treatment in this study suggests that longevity can be further extended than
previously suggested by applying a cyclic and mild stress throughout the life,
depending on the genotype.
PMID- 27488376
TI - Nitric oxide signals are interlinked with calcium signals in normal pancreatic
stellate cells upon oxidative stress and inflammation.
AB - The mammalian diffuse stellate cell system comprises retinoid-storing cells
capable of remarkable transformations from a quiescent to an activated
myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract
attention owing to the pivotal role they play in development of tissue fibrosis
in chronic pancreatitis and pancreatic cancer. However, little is known about the
actual role of PSCs in the normal pancreas. These enigmatic cells have recently
been shown to respond to physiological stimuli in a manner that is markedly
different from their neighbouring pancreatic acinar cells (PACs). Here, we
demonstrate the capacity of PSCs to generate nitric oxide (NO), a free radical
messenger mediating, for example, inflammation and vasodilatation. We show that
production of cytosolic NO in PSCs is unambiguously related to cytosolic Ca(2+)
signals. Only stimuli that evoke Ca(2+) signals in the PSCs elicit consequent NO
generation. We provide fresh evidence for the striking difference between
signalling pathways in PSCs and adjacent PACs, because PSCs, in contrast to PACs,
generate substantial Ca(2+)-mediated and NOS-dependent NO signals. We also show
that inhibition of NO generation protects both PSCs and PACs from necrosis. Our
results highlight the interplay between Ca(2+) and NO signalling pathways in cell
cell communication, and also identify a potential therapeutic target for anti
inflammatory therapies.
PMID- 27488378
TI - What is the Intraarticular Concentration of Tobramycin Using Low-dose Tobramycin
Bone Cement in TKA: An In Vivo Analysis?
AB - BACKGROUND: Antibiotic-impregnated bone cement has increased in popularity as an
effort to reduce the risk of infection in high-risk TKAs. However, limited data
has been reported regarding antibiotic levels achieved when using tobramycin
impregnated bone cement after implanting total knee components.
QUESTIONS/PURPOSES: We asked: (1) What is the tobramycin serum and knee
intraarticular levels in patients undergoing primary TKA using tobramycin cement?
(2) What is the intraarticular tobramycin level for patients receiving only
intravenous tobramycin? METHODS: All patients undergoing primary TKA by one of
the two study surgeons (GV, JP) during a 6-month period were evaluated for
inclusion and invited to participate. The study enrolled 15 patients undergoing
primary TKA by one of two surgeons (GV, JP) who met inclusion criteria; treatment
allocation was assigned randomly through blinded envelope. The study group
consisted of 10 patients whose components were implanted using a commercially
prepared low-dose tobramycin bone cement mixture (1 g/40 g). The control group
consisted of five patients who received standard weight-based dose intravenous
tobramycin. Samples of serum and Hemovac(r) drain-collected intraarticular
hematoma were analyzed at 6, 24, and 48 hours postoperatively. Tobramycin levels
were measured using an immunoassay technique with a low-end sensitivity of 0.28
MUg/mL. Mann-Whitney U tests were performed to compare the serum and
intraarticular tobramycin concentrations at each time in the independent variable
of group (Control and Study). RESULTS: The median (interquartile range [IQR])
intraarticular tobramycin concentrations for the study group, with tobramycin
impregnated bone cement, was 31.8 (29.0) MUg/mL at 6 hours, 17.1 (13.1) MUg/mL at
24 hours, and 6.8 (6.8) MUg/mL at 48 hours. The intraarticular tobramycin
concentrations of this study group were larger than those for the control group
at 6 hours (median = 1.3; IQR = 0.7; p = 0.002), 24 hours (median = 1.3, IQR =
1.0; p = 0.002), and 48 hours (median = 1.4; IQR = 1.0; p = 0.02). The serum
concentrations for the tobramycin-impregnated bone cement group were 0.3 MUg/mL
or less for all samples whereas serum concentrations and median (IQR) for the
control group were 1.2 (2.6) MUg/mL, 1.6 (4.4) MUg/mL, and 2.0 (3.3) MUg/mL at 6,
24, and 48 hours respectively. The serum levels for the tobramycin-impregnated
cement group were less than those for the control group at 6 hours (p = 0.001),
24 (p = 0.001), and 48 hours (p < 0.001). CONCLUSIONS: Tobramycin-impregnated
bone cement provides a way to deliver antibiotics in patients undergoing TKA.
This supratherapeutic short-term prophylactic perioperative antibiotic local
delivery can be achieved with limited systemic absorption, whereas joint
tobramycin levels were less than therapeutic levels when given intravenously
alone. In the control group, with only intravenous tobramycin, a subtherapeutic
(< 2.0 MUg/mL) level of tobramycin was found in all the intraarticular samples at
6, 24, and 48 hours. Based on the evidence obtained in this study, commercially
prepared low-dose tobramycin bone cement can be used to obtain short-term
supratherapeutic local concentrations in the knee while maintaining serum
tobramycin levels at a minimum. LEVEL OF EVIDENCE: Level II, therapeutic study.
PMID- 27488379
TI - Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and
Innervation After Total Disc Replacement in the Lumbar Spine.
AB - BACKGROUND: The pathophysiology and mechanisms driving the generation of
unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh
molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce
inflammation, which may result in pain. QUESTIONS/PURPOSES: The purpose of this
study was to determine whether (1) periprosthetic UHMWPE wear debris induces
immune responses that lead to the production of tumor necrosis factor-alpha
(TNFalpha) and interleukin (IL)-1beta, the vascularization factors, vascular
endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGFbb),
and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2)
the number of macrophages is associated with the production of the aforementioned
factors; (3) the wear debris-induced inflammatory pathogenesis involves an
increase in vascularization and associated innervation. METHODS: Periprosthetic
tissues from our collection of 11 patients with contemporary TDRs were evaluated
using polarized light microscopy to quantify UHMWPE wear particles. The major
reason for revision (mean implantation time of 3 years [range, 1-6 years]) was
pain. For control subjects, biopsy samples from four patients with degenerative
disc disease with severe pain and autopsy samples from three normal patients with
no history of back pain were also investigated. Immunohistochemistry and
histology were used to identify secretory factors, macrophages, and blood
vessels. Immunostained serial sections were imaged at *200 magnification and
using MATLAB and NIH ImageJ, a threshold was determined for each factor and used
to quantify positive staining normalized to tissue sectional area. The Mann
Whitney U test was used to compare results from different patient groups, whereas
the Spearman Rho test was used to determine correlations. Significance was based
on p < 0.05. RESULTS: The mean percent area of all six inflammatory,
vascularization, and innervation factors was higher in TDR tissues when compared
with normal disc tissues. Based on nonparametric data analysis, those factors
showing the most significant increase included TNFalpha (5.17 +/- 1.76 versus
0.05 +/- 0.03, p = 0.02), VEGF (3.02 +/- 1.01 versus 0.02 +/- 0.002, p = 0.02),
and substance P (4.15 +/- 1.01 versus 0.08 +/- 0.04, p = 0.02). The mean percent
area for IL-1beta (2.41 +/- 0.66 versus 0.13 +/- 0.13, p = 0.01), VEGF (3.02 +/-
1.01 versus 0.34 +/- 0.29, p = 0.04), and substance P (4.15 +/- 1.01 versus 1.05
+/- 0.46, p = 0.01) was also higher in TDR tissues when compared with disc
tissues from patients with painful degenerative disc disease. Five of the
factors, TNFalpha, IL-1beta, VEGF, NGF, and substance P, strongly correlated with
the number of wear particles, macrophages, and blood vessels. The most notable
correlations included TNFalpha with wear particles (p < 0.001, rho = 0.63), VEGF
with macrophages (p = 0.001, rho = 0.71), and NGF with blood vessels (p < 0.001,
rho = 0.70). Of particular significance, the expression of PDGFbb, NGF, and
substance P was predominantly localized to blood vessels/nerve fibers.
CONCLUSIONS: These findings indicate wear debris-induced inflammatory reactions
can be linked to enhanced vascularization and associated innervation/pain factor
production at periprosthetic sites around TDRs. Elucidating the pathogenesis of
inflammatory particle disease will provide information needed to identify
potential therapeutic targets and treatment strategies to mitigate pain and
potentially avoid revision surgery. LEVEL OF EVIDENCE: Level III, therapeutic
study.
PMID- 27488380
TI - Thromboprophylaxis using combined intermittent pneumatic compression and
pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically
ill patients: study protocol for a randomized controlled trial.
AB - BACKGROUND: Venous thromboembolism (VTE) remains a common problem in critically
ill patients. Pharmacologic prophylaxis is currently the standard of care based
on high-level evidence from randomized controlled trials. However, limited
evidence exists regarding the effectiveness of intermittent pneumatic compression
(IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism
(PREVENT trial) aims to determine whether the adjunct use of IPC with
pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in
critically ill patients reduces the risk of VTE. METHODS/DESIGN: The PREVENT
trial is a multicenter randomized controlled trial, which will recruit 2000
critically ill patients from over 20 hospitals in three countries. The primary
outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT)
within 28 days after randomization. Radiologists interpreting the scans are
blinded to intervention allocation, whereas the patients and caregivers are
unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in
proximal DVT from 7 to 4 %. DISCUSSION: The first patient was enrolled in July
2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers
in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated
in July 2016. We expect to complete recruitment by 2018. TRIAL REGISTRATION:
Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current
controlled trials: ISRCTN44653506 (registered on 30 October 2013).
PMID- 27488381
TI - Factors associated with late stage at diagnosis among Puerto Rico's government
health plan colorectal cancer patients: a cross-sectional study.
AB - BACKGROUND: Late stage at diagnosis of cancer is considered a key predictor
factor for a lower survival rate. Knowing and understanding the barriers to an
early diagnosis of colorectal cancer is critical in the fight to reduce the
social and economic burden caused by cancer in Puerto Rico. This study evaluates
factors associated to colorectal cancer stage at diagnosis among Puerto Rico's
Government Health Plan (GHP) patients. METHODS: We conducted a cross-sectional
study based on a secondary data analysis using information from the Puerto Rico
Central Cancer Registry (PRCCR) and the Puerto Rico Health Insurance
Administration (PRHIA). Logistic regression models were used to estimate the
unadjusted odds ratio (ORs) and adjusted odds ratio (AORs), and their 95 %
confidence intervals (CIs). Colorectal cancer cases diagnosed between January 1,
2012 and December 31, 2012, among persons 50 to 64 years of age, participants of
the GHP and with a cancer diagnosis reported to the PRCCR were included in the
study. RESULTS: There were 68 (35.79 %) colorectal cancer patients diagnosed at
early stage while 122 (64.21 %) where diagnosed at late stage. In the
multivariate analysis having a diagnostic delay of more than 59 days (AOR 2.94,
95 % CI: 1.32 to 6.52) and having the first visit through the emergency room (AOR
3.48, 95 % CI: 1.60 to 7.60) were strong predictors of being diagnosed with
colorectal cancer at a late stage. CONCLUSIONS: These results are relevant to
understand the factors that influence the outcomes of colorectal cancer patients
in the GHP. Therefore, it is important to continue developing studies to
understand the Government Health Plan patient's pathways to a cancer diagnosis,
in order to promote assertive decisions to improve patient outcomes.
PMID- 27488382
TI - Anti-erythrocyte antibodies may contribute to anaemia in Plasmodium vivax malaria
by decreasing red blood cell deformability and increasing erythrophagocytosis.
AB - BACKGROUND: Plasmodium vivax accounts for the majority of human malaria
infections outside Africa and is being increasingly associated in fatal outcomes
with anaemia as one of the major complications. One of the causes of malarial
anaemia is the augmented removal of circulating non-infected red blood cells
(nRBCs), an issue not yet fully understood. High levels of auto-antibodies
against RBCs have been associated with severe anaemia and reduced survival of
nRBCs in patients with falciparum malaria. Since there are no substantial data
about the role of those antibodies in vivax malaria, this study was designed to
determine whether or not auto-antibodies against erythrocytes are involved in
nRBC clearance. Moreover, the possible immune mechanisms elicited by them that
may be associated to induce anaemia in P. vivax infection was investigated.
METHODS: Concentrations of total IgG were determined by sandwich ELISA in sera
from clinically well-defined groups of P. vivax-infected patients with or without
anaemia and in healthy controls never exposed to malaria, whereas the levels of
specific IgG to nRBCs were determined by cell-ELISA. Erythrophagocytosis assay
was used to investigate the ability of IgGs purified from each studied pooled
sera in enhancing nRBC in vitro clearance by THP-1 macrophages. Defocusing
microscopy was employed to measure the biomechanical modifications of individual
nRBCs opsonized by IgGs purified from each group. RESULTS: Anaemic patients had
higher levels of total and specific anti-RBC antibodies in comparison to the non
anaemic ones. Opsonization with purified IgG from anaemic patients significantly
enhanced RBCs in vitro phagocytosis by THP-1 macrophages. Auto-antibodies
purified from anaemic patients decreased the nRBC dynamic membrane fluctuations
suggesting a possible participation of such antibodies in the perturbation of
erythrocyte flexibility and morphology integrity maintenance. CONCLUSIONS: These
findings revealed that vivax-infected patients with anaemia have increased levels
of IgG auto-antibodies against nRBCs and that their deposition on the surface of
non-infected erythrocytes decreases their deformability, which, in turn, may
enhance nRBC clearance by phagocytes, contributing to the anaemic outcome. These
data provide insights into the immune mechanisms associated with vivax malaria
anaemia and may be important to the development of new therapy and vaccine
strategies.
PMID- 27488383
TI - The role of positron emission tomography in the evaluation of myocardial ischemia
in women.
AB - Cardiovascular disease continues to be the number one cause of death in women,
yet most women are unaware of their risk. Over the last decade, radionuclide
myocardial perfusion imaging with positron emission tomography (PET) has become a
powerful tool for the diagnosis and risk stratification of patients with known or
suspected coronary artery disease (CAD). This editorial viewpoint will review the
maturing role of PET imaging in women, particularly as applied to the evaluation
of ischemic heart disease. Specifically, we focus on distinct advantages offered
by PET imaging in the evaluation of myocardial ischemia in women: (1) improved
diagnostic accuracy, including in the presence of breast or adipose tissue and
small left ventricular cavity size, (2) decreased radiation exposure through the
use of short-lived radiopharmaceuticals, and (3) the ability to quantify
myocardial blood flow and coronary flow reserve to diagnose ischemia, even in the
absence of obstructive CAD. As such, cardiac PET perfusion imaging stands to play
a unique role in defining the diagnosis and prognosis of women with ischemic
heart disease, while also guiding new treatment strategies for their more
prevalent cardiovascular disease phenotypes.
PMID- 27488384
TI - How do we manage blood product support in the massively hemorrhaging obstetric
patient?
AB - Obstetric hemorrhage remains a leading cause of maternal mortality with more than
140,000 deaths annually worldwide. Abnormal placentation has increased to become
the most common diagnosis requiring massive blood transfusion in obstetrics, with
uterine atony a close second. At our institution, as well as nationwide, there
has been a steady increase in pregnancies complicated by abnormal placentation,
including accreta, increta, and percreta. Providers at our facility created the
New England Center for Placental Disorders in May 2015 to address these complex
patients. The incidence of accreta has actually increased 10-fold over the past
50 years, becoming the most common reason for cesarean hysterectomy in highly
industrialized countries. The most common risk factor for accreta is repeat
cesarean sections, particularly those with associated placenta previa.
Contemporary cesarean section rates have risen, with more than 1.2 million women
having had a cesarean section in the United States in 2014. We present a case
vignette of a multiparous woman presenting with heavy vaginal bleeding at 30
weeks' gestation with imaging concerning for placenta accreta and possible
percreta. We describe our approach to the management of these complicated
patients.
PMID- 27488385
TI - Effect of eliminating open defecation on diarrhoeal morbidity: an ecological
study of Nyando and Nambale sub-counties, Kenya.
AB - BACKGROUND: Defecating in the open predisposes people to soil transmitted
helminthes and diarrhoeal diseases. An estimated 5.6 million Kenyans defecate in
the open. Kenya launched a program to eradicate open defecation by 2013 in the
rural areas. By end of 2013, only two sub-counties had eliminated open
defecation. These are Nambale and Nyando. The study looked at the impact of
eradicating open defecation on diarrhea prevalence among children in these two
sub-counties. METHODS: Data on diarrhoea morbidity among children under 5 years
was extracted from the Kenya Health Information System for all the sub-counties
in Busia and Kisumu counties for 2012, 2013 and 2014 respectively. Prevalence was
calculated for each sub-county in Kisumu for comparison with Nyando's. Prevalence
was also calculated for each sub-county in Busia County and compared to that of
Nambale sub-county. A Mann-Whitney U Test was done to test the null hypothesis
that diarrhoea prevalence was similar in both open defecation and open defecation
free sub-counties. RESULTS: A Mann-Whitney U Test revealed significant difference
in diarrhoeal prevalence of open defecation sub-counties (Md = 18.4, n = 34) and
open defecation free sub-counties (Md = 9.8, n = 5), U = 9, z = -3.2, p = .001.
Among the two Counties, Nambale had the lowest prevalence. It recorded a decline
from 9.8 to 5.7 % across the three years. Prevalence for diarrhoea cases in
Nyando declined from 19.1 to 15.2 % across the three years. Nyando initially had
the second highest prevalence in Kisumu County and by 2014 it had the lowest
prevalence. CONCLUSIONS: The two sub-counties with open defecation free status
had lower prevalence of diarrhoea cases compared to sub-counties which were yet
to attain open defecation free status. This suggests that elimination of open
defecation may reduce the number of diarrhoea cases.
PMID- 27488386
TI - A comparison of different functions for predicted protein model quality
assessment.
AB - In protein structure prediction, a considerable number of models are usually
produced by either the Template-Based Method (TBM) or the ab initio prediction.
The purpose of this study is to find the critical parameter in assessing the
quality of the predicted models. A non-redundant template library was developed
and 138 target sequences were modeled. The target sequences were all distant from
the proteins in the template library and were aligned with template library
proteins on the basis of the transformation matrix. The quality of each model was
first assessed with QMEAN and its six parameters, which are C_beta interaction
energy (C_beta), all-atom pairwise energy (PE), solvation energy (SE), torsion
angle energy (TAE), secondary structure agreement (SSA), and solvent
accessibility agreement (SAE). Finally, the alignment score (score) was also used
to assess the quality of model. Hence, a total of eight parameters (i.e., QMEAN,
C_beta, PE, SE, TAE, SSA, SAE, score) were independently used to assess the
quality of each model. The results indicate that SSA is the best parameter to
estimate the quality of the model.
PMID- 27488387
TI - Catalytic asymmetric bromochlorination of aromatic allylic alcohols promoted by
multifunctional Schiff base ligands.
AB - It was found that the tridentate O,N,O-type Schiff base ligand bearing suitable
substituents was a highly effective promoter in the catalytic asymmetric
bromochlorination reaction, in which the corresponding aromatic
bromochloroalcohols with vicinal halogen-bearing stereocenters were formed with
perfect regioselectivity, with moderate to excellent enantioselectivities (up to
93% ee), and with good yields and chemoselectivities.
PMID- 27488388
TI - Adherence to antidepressants among women and men described with trajectory
models: a Swedish longitudinal study.
AB - PURPOSE: The purpose of this study are to analyse adherence to antidepressant
treatment over 2 years in Sweden among women and men who initiated treatment with
citalopram and to identify groups at risk of non-adherence using trajectory
models. METHODS: The study population, including individuals 18-85 years who
initiated citalopram use between 1 July 2006 and 30 June 2007, was identified in
the Swedish Prescribed Drug Register and followed for 2 years. Adherence was
estimated with continuous measure of medication acquisition (CMA) and group-based
trajectory modelling, a method which describes adherence patterns over time by
estimating trajectories of adherence and the individual's probability of
belonging to a specific trajectory. RESULTS: The study population included 54,248
individuals, 64 % women. Mean CMA was 52 % among women and 50 % among men (p <
0.001). Five different adherence patterns (Trajectories) were identified. Similar
proportion of women and men belonged to each Trajectory. Around 29 % of the women
and 27 % of the men belonged to the Trajectory which showed full adherence
throughout the 2-year study period. The other four Trajectories showed adherence
that declined to different degrees and at different stages in time. Having low
socioeconomic status was more common among individuals in Trajectories showing
declining adherence than in the adherent Trajectory. CONCLUSIONS: Using
trajectory modelling, five Trajectories describing different patterns of
adherence to citalopram treatment over time were identified. A large proportion
discontinued treatment early and having low socioeconomic status increased the
risk of being non-adherent.
PMID- 27488389
TI - Influence of genetic polymorphisms in cytochrome P450 oxidoreductase on the
variability in stable warfarin maintenance dose in Han Chinese.
AB - PURPOSE: The aim of this study was to investigate whether any of the single
nucleotide polymorphisms (SNPs) in the POR gene were significantly associated
with CYP activity and expression, and could contribute to the total variability
in stable warfarin maintenance doses in Han Chinese. METHODS: A total of 408
patients treated at the First Affiliated Hospital of Sun Yat-Sen University were
eligible for the study and had attained a stable warfarin maintenance dose at the
start of the investigation. Demographics, warfarin maintenance doses, and
concomitant medications were documented. Genomic DNA was extracted from
peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2
rs2108622, VKORC1 -1639C>T, and potential POR genes of rs10239977, rs3815455,
rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY
genotyping system. RESULTS: A predictive model of warfarin maintenance dose was
established and indicated that age, gender, body surface area, aspirin use,
CYP2C9*3, CYP4F2 rs2108622, VKORC1 -1639C>T, and POR*37 831-35C>T accounted for
42.4 % of dose variance in patients undergoing anticoagulant treatment. The
contribution of POR*37 831-35C>T to warfarin dose variation was only 3.9 %.
CONCLUSIONS: For the first time, the SNP POR*37 831-35C>T was confirmed as a
minor but statistically significant factor associated with interindividual
variation in warfarin maintenance dose in Han Chinese. The POR*37 gene
polymorphism should be considered in future algorithms for faster and more
reliable achievement of stable warfarin maintenance doses.
PMID- 27488390
TI - The GOOD life: Study protocol for a social norms intervention to reduce alcohol
and other drug use among Danish adolescents.
AB - BACKGROUND: It is currently unknown if school-based social norms interventions
are effective in preventing harmful alcohol consumption and other drug use among
adolescents in Denmark. This paper describes the social norms-based programme The
GOOD life and the design of a cluster-randomized controlled trial to test its
effectiveness. METHODS/DESIGN: The intervention The GOOD life is composed of
three social norms components representing three different communication
channels, namely face-to-face communication (normative feedback session), print
communication (posters) and interactive media (web application). The intervention
period of 8 weeks is preceded and followed by data collection, with the follow-up
taking place 3 months after baseline. Public schools in the Region of Southern
Denmark with grades 8 and 9 are invited to participate in the study and
participating schools are randomly allocated to either intervention or control
schools. The aim is to recruit a total of 39 schools and a sample of 1.400 pupils
for the trial. An online questionnaire is conducted to examine the use of
alcohol, tobacco and marijuana as well as the perceived frequency of use among
peers of their own grade, which is measured before and after the intervention.
Baseline data is used to develop social norms messages which are included in the
three intervention components. Primary outcomes are binge drinking (more than 5
units at one occasion) and perceived frequency of binge drinking among peers,
while smoking, marijuana use and alcohol-related harm will be assessed as
secondary outcomes. DISCUSSION: The GOOD life study will provide necessary
insights on descriptive and injunctive norms regarding alcohol and other drug use
among Danish adolescents. In addition, it will provide new knowledge and insight
on the feasibility, implementation context and effectiveness of a newly developed
social norms intervention in the Danish school context. TRIAL REGISTRATION: Date
of registration: 17 February 2016 (retrospectively registered) at Current
Controlled Trials with study ID ISRCTN27491960.
PMID- 27488391
TI - Multi-organ benign and malignant tumors: recognizing Cowden syndrome: a case
report and review of the literature.
AB - BACKGROUND: Cowden syndrome is an autosomal dominant disorder with a
predisposition to multiple benign and malignant tumors. In our patient, in
addition to breast and endometrial malignancies as well as facial trichilemmomas,
she was noted to have multiple meningiomas, pancreatic lipomas and lung cysts.
These latter lesions have been noted in previous Cowden syndrome case reports,
but are not included in the diagnostic criteria at this time. To our knowledge,
this is the first case of multiple meningiomas in this syndrome. Further studies
are therefore warranted to assess the significance of these findings in Cowden
syndrome. CASE PRESENTATION: A middle-aged Afro-Caribbean known endometrial
carcinoma patient (post surgery and adjuvant radiotherapy), presented with a
locally advanced breast carcinoma. She received neoadjuvant chemotherapy followed
by a modified radical mastectomy and axillary lymph node clearance. Her past
medical history included a sphenoid wing meningioma for which she received
definitive external beam radiotherapy. She was also known to have a multinodular
goiter, anal polyp and longstanding mucocutaneous lesions. Further workup
revealed additional smaller meningiomas, a parotid arteriovenous malformation, a
lung cyst and pancreatic lipomas. Overall, consortium criteria were met for the
diagnosis of Cowden syndrome. Furthermore, genetic testing identified a
pathogenic mutation in the PTEN gene. She will be closely followed with annual
clinical examination, dermatologic assessment and screening colonoscopies. She
will perform interval whole body contrast enhanced CT for continued surveillance
for metastatic disease. CONCLUSION: Cowden syndrome is likely to be an under
diagnosed condition, but critically important to identify due to its cancer
predisposition. When encountering multi-organ tumors, diagnostic criteria for
Cowden syndrome should be sought in order to increase the diagnostic rates.
Cancer surveillance for carcinoma detection in the early and curative stages
remains the most critical aspect of management.
PMID- 27488392
TI - Cognitive Bias Modification Training During Inpatient Alcohol Detoxification
Reduces Early Relapse: A Randomized Controlled Trial.
AB - BACKGROUND: Relapse is common in alcohol-dependent individuals and can be
triggered by alcohol-related cues in the environment. It has been suggested that
these individuals develop cognitive biases, in which cues automatically capture
attention and elicit an approach action tendency that promotes alcohol seeking.
The study aim was to examine whether cognitive bias modification (CBM) training
targeting approach bias could be delivered during residential alcohol
detoxification and improve treatment outcomes. METHODS: Using a 2-group parallel
block (ratio 1:1) randomized controlled trial with allocation concealed to the
outcome assessor, 83 alcohol-dependent inpatients received either 4 sessions of
CBM training where participants were implicitly trained to make avoidance
movements in response to pictures of alcoholic beverages and approach movements
in response to pictures of nonalcoholic beverages, or 4 sessions of sham training
(controls) delivered over 4 consecutive days during the 7-day detoxification
program. The primary outcome measure was continuous abstinence at 2 weeks
postdischarge. Secondary outcomes included time to relapse, frequency and
quantity of alcohol consumption, and craving. Outcomes were assessed in a
telephonic follow-up interview. RESULTS: Seventy-one (85%) participants were
successfully followed up, of whom 61 completed all 4 training sessions. With an
intention-to-treat approach, there was a trend for higher abstinence rates in the
CBM group relative to controls (69 vs. 47%, p = 0.07); however, a per-protocol
analysis revealed significantly higher abstinence rates among participants
completing 4 sessions of CBM relative to controls (75 vs. 45%, p = 0.02). Craving
score, time to relapse, mean drinking days, and mean standard drinks per drinking
day did not differ significantly between the groups. CONCLUSIONS: This is the
first trial demonstrating the feasibility of CBM delivered during alcohol
detoxification and supports earlier research suggesting it may be a useful, low
cost adjunctive treatment to improve treatment outcomes for alcohol-dependent
patients.
PMID- 27488393
TI - Solution NMR structures of the C-domain of Tetrahymena cytoskeletal protein Tcb2
reveal distinct calcium-induced structural rearrangements.
AB - Tcb2 is a calcium-binding protein that localizes to the membrane-associated
skeleton of the ciliated protozoan Tetrahymena thermophila with hypothesized
roles in ciliary movement, cell cortex signaling, and pronuclear exchange. Tcb2
has also been implicated in a unique calcium-triggered, ATP-independent type of
contractility exhibited by filamentous networks isolated from the Tetrahymena
cytoskeleton. To gain insight into Tcb2's structure-function relationship and
contractile properties, we determined solution NMR structures of its C-terminal
domain in the calcium-free and calcium-bound states. The overall architecture is
similar to other calcium-binding proteins, with paired EF-hand calcium-binding
motifs. Comparison of the two structures reveals that Tcb2-C's calcium-induced
conformational transition differs from the prototypical calcium sensor
calmodulin, suggesting that the two proteins play distinct functional roles in
Tetrahymena and likely have different mechanisms of target recognition. Future
studies of the full-length protein and the identification of Tcb2 cellular
targets will help establish the molecular basis of Tcb2 function and its unique
contractile properties. Proteins 2016; 84:1748-1756. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27488394
TI - Effect of ramosetron on QTc interval: a randomised controlled trial in patients
undergoing off-pump coronary artery bypass surgery.
AB - BACKGROUND: Ramosetron is a relatively new 5-hydroxytryptamine three receptor
antagonist with higher binding affinity and more prolonged duration of action
compared to ondansetron. The present study was performed to evaluate the effects
of ramosetron on QTc interval and possible cardiovascular adverse effects in
patients undergoing cardiac surgery. METHOD: A total of 114 patients who
underwent off-pump coronary artery bypass surgery were enrolled in this
randomised placebo-controlled trial. Patients were allocated into two groups that
received intravenous injection of 0.3 mg ramosetron or normal saline during
induction of anaesthesia. QTc intervals were measured before the operation,
intraoperatively (0, 1, 2, 3, 5, 10, 15, 30, 45, 60, 90, 120, and 240 min after
injection of ramosetron or normal saline), at the end of the operation, and on
postoperative day 1. RESULTS: There were no differences in mean QTc interval
between groups at every time point. However, maximal change in QTc interval
during surgery was higher in the ramosetron group than the placebo group (25.1 +/
22.0 vs. 17.5 +/- 14.5 ms, 95 % CI 0.34-14.78, P = 0.040). Also, there were more
patients with a QTc interval increase of > 60 ms in the ramosetron group (5 vs.
0, 95 % CI 1.6-18.0, P = 0.021). There were no significant differences in
cardiovascular complications. CONCLUSIONS: Ramosetron administered during
induction of anaesthesia may affect maximal change in QTc interval during off
pump coronary artery bypass surgery. Ramosetron should be used with caution in
high risk patients for developing Torsades de Pointes. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02139241. Registered November 12, 2013.
PMID- 27488395
TI - DEF6 expression in ovarian carcinoma correlates with poor patient survival.
AB - BACKGROUND: Increased expression of DEF6 is correlated with the malignant
behavior of various cancers. Both DEF6 and p16 contribute to the regulation of
cell cycle progression, and p53 plays important role in the cell cycle
checkpoints. This study was designed to elucidate the prognostic significance of
DEF6, p53 and p16 immunoexpressions in different histology subtypes of ovarian
carcinoma. METHODS: Immunohistochemistry results of DEF6, p53 and p16 on ovarian
carcinoma were compared with histology subtypes, clinical data, overall survival
(OS) and disease-free survival (DFS) by Cox regression and Kaplan-Meier analysis.
RESULTS: We studied 180 cases of ovarian carcinomas (75 high-grade serous, 41
clear cell, 36 mucinous and 28 endometrioid), including 109 FIGO stage I-II cases
and 71 FIGO stage III-IV cases. Ovarian carcinomas positive for both DEF6 and p16
expression were associated with the worst OS (P = 0.027) and DFS (P = 0.023),
whereas those negative for both DEF6 and p16 had the best OS and DFS. Aberrant
p53 expression combined with positive DEF6 was associated with worst OS (P =
0.031) and DFS (P = 0.028). Kaplan-Meier analysis showed that significantly
shorter survival rates were seen in patients with high expressions of DEF6 (P =
0.008) and p16 (P = 0.022). Patients with aberrant p53 expression in high-grade
serous carcinoma (P = 0.012) and patients with high DEF6 expression in clear cell
carcinoma (P = 0.001) were also associated with shorter overall survival. In
univariate analysis, FIGO stage, DEF6 and p16 were associated with poor
prognosis. DEF6 expression was the only independent prognostic factor correlated
with shorted OS (HR 2.115; P = 0.025) and DFS (HR 2.248; P = 0.016) upon
multivariate analysis. CONCLUSIONS: DEF6 expression may serve as an independent
prognostic factor, and interacted positively with p16 toward high tumor stage and
shorter survival.
PMID- 27488396
TI - The potential of chondrogenic pre-differentiation of adipose-derived mesenchymal
stem cells for regeneration in harsh nucleus pulposus microenvironment.
AB - Recent studies indicated that cell-based therapy could be a promising approach to
treat intervertebral disc degeneration. Though the harsh microenvironment in disc
is still challenging to implanted cells, it could be overcome by pre-conditioning
graft cells before transplantation, suggested by previous literatures. Therefore,
we designed this study to identify the potential effect of chondrogenic pre
differentiation on adipose-derived mesenchymal stem cells in intervertebral disc
like microenvironment, characterized by limited nutrition, acidic, and high
osmosis in vitro. Adipose-derived mesenchymal stem cells of rat were divided into
five groups, embedded in type II collagen scaffold, and cultured in chondrogenic
differentiation medium for 0, 3, 7, 10, and 14 days. Then, the adipose-derived
mesenchymal stem cells were implanted and cultured in intervertebral disc-like
condition. The proliferation and differentiation of adipose-derived mesenchymal
stem cells were evaluated by cell counting kit-8 test, real-time quantitative
polymerase chain reaction, and Western blotting and immunofluorescence analysis.
Analyzed by the first week in intervertebral disc-like condition, the results
showed relatively greater proliferative capability and extracellular matrix
synthesis ability of the adipose-derived mesenchymal stem cells pre
differentiated for 7 and 10 days than the control. We concluded that pre
differentiation of rat adipose-derived mesenchymal stem cells in chondrogenic
culture medium for 7 to 10 days could promote the regeneration effect of adipose
derived mesenchymal stem cells in intervertebral disc-like condition, and the pre
differentiated cells could be a promising cell source for disc regeneration
medicine.
PMID- 27488397
TI - GSK and Google form partnership to develop bioelectronic medicines.
PMID- 27488398
TI - Investigation of cobalt(iii)-triazole systems as prototypes for hypoxia-activated
drug delivery.
AB - Three novel cobalt(iii)-triazole complexes with structural and redox properties
suitable for hypoxia-activated drug delivery were obtained. A major influence of
the ancillary ligands (TPA, py2en, py2enMe2) on the electronic properties and
reactivity of their complexes was observed. An [O2]-dependent reduction to
cobalt(ii) by ascorbic acid provided evidence of hypoxic selectivity.
PMID- 27488399
TI - Monocytes and Macrophages: A Fresh Look at Functional and Phenotypic Diversity.
AB - This Forum addresses the functional and phenotypical diversity of monocytes and
macrophages and explores new mechanisms that contribute to the plasticity of
these cells. The contributors provide in-depth and comprehensive overviews on
selected key mechanisms underlying macrophage plasticity and diversity and how
they related to human disease and aging. What emerges from these contributions is
the importance of the interactions of macrophages with their dynamic
microenvironment and the need for a better mechanistic understanding of how these
cells sense environmental cues, integrate and respond to these signals, and
thereby themselves help shape their microenvironment. Antioxid. Redox Signal. 25,
756-757.
PMID- 27488400
TI - Where do you come from and what are you going to become, reactive astrocyte?
PMID- 27488401
TI - Genotype Frequencies of CYP2C19, P2Y12 and GPIIIa Polymorphisms in Coronary Heart
Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel
Responsiveness.
AB - To investigate the genotype frequencies of cytochrome P450, family2, subfamily C,
polypeptide19 (CYP2C19); P2Y12 receptor; and glycoprotein IIIa polymorphisms in
patients with coronary heart disease and their impact on clopidogrel
responsiveness and major adverse cardiac events (MACEs).A total of 146 coronary
heart disease patients of Han ethnicity, on a clopidogrel regimen, were enrolled.
Polymerase chain reaction and DNA sequencing were used to detect the genotype and
allelic frequencies of CYP2C19 ((*)2,(*)3,(*)17), P2Y12 (C34T, G52T, T744C) and
GPIIIa (T1565C) polymorphisms. Clinical and laboratory data were compared between
the high on-treatment platelet reactivity (HTPR) versus normal groups.HTPR was
identified in 35 (24%) patients. CYP2C19(*)2 (G681A) polymorphism was found to be
significantly associated with HTPR (P < 0.05). A allele frequencies were
significantly higher in the HTPR group versus the normal group (P < 0.05). On
logistic regression analysis, CYP2C19(*)2 (G681A) polymorphism was found to be an
independent risk factor associated with HTPR. No link could be established
between genetic polymorphisms and recurrence of MACEs, or between HTPR and
recurrence of MACEs.The genetic polymorphisms in CYP2C19(*)2 were closely
associated with HTPR. The frequency of the A allele of CYP2C19(*)2 was
significantly associated with HTPR, with A allele carriers being more likely to
develop HTPR.
PMID- 27488404
TI - Health Concept and Knowledge Management: Twenty-five Years of Evolution.
AB - OBJECTIVES: The fields of health terminology, classification, ontology, and
related information models have evolved dramatically over the past 25 years. Our
objective was to review notable trends, described emerging or enabling
technologies, and highlight major terminology systems during the interval.
METHODS: We review the progression in health terminology systems informed by our
own experiences as part of the community involved in this work, reinforced with
literature review and citation. RESULTS: The transformation in size, scope,
complexity, and adoption of health terminological systems and information models
has been tremendous, on the scale of orders of magnitude. CONCLUSION: The present
"big science" era of inference and discovery in biomedicine would not have been
possible or scalable absent the growth and maturation of health terminology
systems and information models over the past 25 years.
PMID- 27488403
TI - Progress in Biomedical Knowledge Discovery: A 25-year Retrospective.
AB - OBJECTIVES: We sought to explore, via a systematic review of the literature, the
state of the art of knowledge discovery in biomedical databases as it existed in
1992, and then now, 25 years later, mainly focused on supervised learning.
METHODS: We performed a rigorous systematic search of PubMed and latent Dirichlet
allocation to identify themes in the literature and trends in the science of
knowledge discovery in and between time periods and compare these trends. We
restricted the result set using a bracket of five years previous, such that the
1992 result set was restricted to articles published between 1987 and 1992, and
the 2015 set between 2011 and 2015. This was to reflect the current literature
available at the time to researchers and others at the target dates of 1992 and
2015. The search term was framed as: Knowledge Discovery OR Data Mining OR
Pattern Discovery OR Pattern Recognition, Automated. RESULTS: A total 538 and
18,172 documents were retrieved for 1992 and 2015, respectively. The number and
type of data sources increased dramatically over the observation period,
primarily due to the advent of electronic clinical systems. The period 1992- 2015
saw the emergence of new areas of research in knowledge discovery, and the
refinement and application of machine learning approaches that were nascent or
unknown in 1992. CONCLUSIONS: Over the 25 years of the observation period, we
identified numerous developments that impacted the science of knowledge
discovery, including the availability of new forms of data, new machine learning
algorithms, and new application domains. Through a bibliometric analysis we
examine the striking changes in the availability of highly heterogeneous data
resources, the evolution of new algorithmic approaches to knowledge discovery,
and we consider from legal, social, and political perspectives possible
explanations of the growth of the field. Finally, we reflect on the achievements
of the past 25 years to consider what the next 25 years will bring with regard to
the availability of even more complex data and to the methods that could be, and
are being now developed for the discovery of new knowledge in biomedical data.
PMID- 27488406
TI - Number of negative lymph nodes as a prognostic factor in esophageal squamous cell
carcinoma.
AB - INTRODUCTION: The aim of this study is to investigate the number of negative
lymph nodes (NLNs) as a prognostic factor for survival in patients with resected
esophageal squamous cell carcinoma. METHODS: A total of 381 esophageal squamous
cell carcinoma patients who had underwent surgical resection as the primary
treatment was enrolled into this retrospective study. The impact of number of
NLNs on patient's overall survival was assessed and compared with the factors
among the current tumor-nodes-metastasis (TNM) staging system. RESULTS: The
number of NLNs was closely related to the overall survival, and the 5-year
survival rate was 45.4% for number of NLNs of >20 (142 cases) and 26.4% for NLNs
<= 20 (239 cases) (P = 0.001). In multivariate survival analysis, the number of
NLNs remained an independent prognostic factor (P = 0.002) as did the other
current TNM factors. For subgroup analysis, the predictive value of number of
NLNs was significant in patients with T3 or T4 disease (P = 0.001) and patients
with N1 and N2-3 disease (P = 0.025, 0.043), but not in patients with T1 or T2
disease or patients with N0 disease. CONCLUSIONS: The number of NLNs, which
represents the extent of lymphadenectomy for esophageal squamous cell carcinoma,
could impact the overall survival of patients with resected esophageal squamous
cell carcinoma, especially among those with nodal-positive disease and advanced T
stage tumor.
PMID- 27488402
TI - Clinical Decision Support: a 25 Year Retrospective and a 25 Year Vision.
AB - OBJECTIVE: The objective of this review is to summarize the state of the art of
clinical decision support (CDS) circa 1990, review progress in the 25 year
interval from that time, and provide a vision of what CDS might look like 25
years hence, or circa 2040. METHOD: Informal review of the medical literature
with iterative review and discussion among the authors to arrive at six axes
(data, knowledge, inference, architecture and technology, implementation and
integration, and users) to frame the review and discussion of selected barriers
and facilitators to the effective use of CDS. RESULT: In each of the six axes,
significant progress has been made. Key advances in structuring and encoding
standardized data with an increased availability of data, development of
knowledge bases for CDS, and improvement of capabilities to share knowledge
artifacts, explosion of methods analyzing and inferring from clinical data,
evolution of information technologies and architectures to facilitate the broad
application of CDS, improvement of methods to implement CDS and integrate CDS
into the clinical workflow, and increasing sophistication of the end-user, all
have played a role in improving the effective use of CDS in healthcare delivery.
CONCLUSION: CDS has evolved dramatically over the past 25 years and will likely
evolve just as dramatically or more so over the next 25 years. Increasingly, the
clinical encounter between a clinician and a patient will be supported by a wide
variety of cognitive aides to support diagnosis, treatment, care-coordination,
surveillance and prevention, and health maintenance or wellness.
PMID- 27488405
TI - Biomedical and Health Informatics Education - the IMIA Years.
AB - OBJECTIVE: This paper presents the development of medical informatics education
during the years from the establishment of the International Medical Informatics
Association (IMIA) until today. METHOD: A search in the literature was performed
using search engines and appropriate keywords as well as a manual selection of
papers. The search covered English language papers and was limited to search on
papers title and abstract only. RESULTS: The aggregated papers were analyzed on
the basis of the subject area, origin, time span, and curriculum development, and
conclusions were drawn. CONCLUSIONS: From the results, it is evident that IMIA
has played a major role in comparing and integrating the Biomedical and Health
Informatics educational efforts across the different levels of education and the
regional distribution of educators and institutions. A large selection of
references is presented facilitating future work on the field of education in
biomedical and health informatics.
PMID- 27488408
TI - Disruption of YLR162W in Saccharomyces cerevisiae results in increased tolerance
to organic solvents.
AB - OBJECTIVE: To identify a novel gene responsible for organic solvent-tolerance by
screening a transposon-mediated deletion mutant library based on Saccharomyces
cerevisiae L3262. RESULTS: One strain tolerant of up to 0.5 % (v/v) n-hexane and
cyclohexane was isolated. The determination of transposon insertion site
identified one gene, YLR162W, and revealed disruption of the ORF of this gene,
indicating that organic solvent tolerance can be conferred. Such a tolerant
phenotype reverted to the sensitive phenotype on the autologous or overexpression
of this gene. This transposon mutant grew faster than the control strain when
cultured at 30 degrees C in YPD medium containing 0.5 % (v/v) n-hexane and
cyclohexane respectively. CONCLUSION: Disruption of YLR162W in S. cerevisiae
results in increased tolerance to organic solvents.
PMID- 27488409
TI - Erratum to: In Vitro Methods for Studying the Mechanisms of Resistance to DNA
Damaging Therapeutic Drugs.
PMID- 27488410
TI - Case report: small cell transformation and metastasis to the breast in a patient
with lung adenocarcinoma following maintenance treatment with epidermal growth
factor receptor tyrosine kinase inhibitors.
AB - BACKGROUND: Breast metastasis from lung cancer has been reported, but not from
SCLC that is transformed from lung adenocarcinoma during maintenance treatment
with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Transformation to small cell lung cancer(SCLC), although uncommonly seen, has
been associated with resistance to EGFR-TKI therapy in lung adenocarcinomas. CASE
PRESENTATION: We describe a case of a 49-year-old man with lung adenocarcinoma
harboring L858R point mutation at the exon 21 of the epidermal growth factor
receptor (EGFR). During the maintenance treatment with EGFR-TKI, the patient
presented with a right breast mass, which was accompanied by elevated serum
neuron specific enolase (NSE) level. The histological examination of biopsies
from the breast mass and enlarging lung mass revealed SCLC that was less
sensitive to standard SCLC treatment. The breast tumor was positive for thyroid
transcription factor-1 (TTF-1), consistent with a lung primary cancer.
CONCLUSION: This is the first case report of small cell transformation and
metastatic to the breast in a patient with lung adenocarcinoma following EGFR-TKI
treatment. Repeat biopsy is important for evaluation of evolving genetic and
histologic changes and selection of appropriate treatment. and serum NSE
measurement may be useful for detection of small cell transformation in cases
with resistance to EGFR-TKI therapy.
PMID- 27488411
TI - Cool Runnings - an app-based intervention for reducing hot drink scalds: study
protocol for a randomised controlled trial.
AB - BACKGROUND: Globally, burns are the fifth leading cause of non-fatal children's
injuries, and the leading cause of childhood burns is hot beverage scalds.
Although there have been a number of programmes aimed at preventing scalds in
children, very few have specifically addressed hot beverage scalds, and fewer
have reported a reduction in injury rates. In Australia, hot beverage scalds
account for 18 % of all childhood burns - a figure that has remained constant for
the past decade. Innovative new technologies, such as Smartphone applications
(apps), present a novel way for delivering individual-level injury prevention
messages. The low cost, scalability and broad reach make this technology an ideal
channel for health interventions. One of the latest methods being used in health
related apps aimed at behaviour change is gamification. Gamification uses the
gaming principles of rewards, competition and personalisation to engage
participants and motivate them towards preferred behaviours. This intervention
will use a Smartphone app-based platform that combines gamification and behaviour
change strategies to increase knowledge and awareness of hot beverage scald risks
and burn first aid among mothers of young children. METHODS/DESIGN: This is a two
group, parallel, single-blinded randomised control trial (RCT) to evaluate the
efficacy of a Smartphone app-based injury prevention intervention. The primary
outcome measure is change in knowledge. Change in knowledge is measured in three
components: knowledge of correct burns first aid; knowledge of the main cause of
burns/scalds in children aged 0-15yrs; knowledge of the main age group at risk
for burns/scalds. The secondary outcome measures relate to the gamification
methods, measuring participants frequency of engagement with the Cool Runnings
app. Queensland-based mothers aged 18+ years who own a Smartphone and have at
least one child aged 5-12 months are eligible to participate. DISCUSSION: To our
knowledge, this is the first study to evaluate an app-based delivery of injury
prevention messages, and the first study to test the efficacy of gamification
techniques in an injury prevention intervention. If this intervention is found to
be effective, this RCT will provide a platform for targeting other childhood
injury prevention campaigns. TRIAL REGISTRATION: This trial was registered on 14
January 2016 with the Australian New Zealand Clinical Trials Registry (
ACTRN12616000019404 ).
PMID- 27488412
TI - Implementation challenges in delivering team-based care ('TEAMcare') for patients
with chronic obstructive pulmonary disease in a public hospital setting: a mixed
methods approach.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is considered a
multisystem disease, in which comorbidities feature prominently. COPD guidelines
recommend holistic assessment and management of relevant comorbid diseases but
there is limited information as to how this is best achieved. This pilot study
aimed to explore the views of stakeholders, including patients and the healthcare
team, on the feasibility, acceptability and barriers to a collaborative,
multidisciplinary team-based care intervention ('TEAMcare') to improve health
outcomes in COPD patients, within the context of a local hospital outpatient
clinic. METHODS: A mixed methods study design was used. A COPD care algorithm was
developed based on the Australasian guidelines, COPDX. COPD participants were
consecutively recruited from an outer metropolitan hospital's respiratory clinic.
Participants attended for follow up visits at 5 and 10 months to ascertain
clinical status, algorithm compliance and to review and revise management
recommendations. The intervention was conducted using existing resources,
involving collaboration with general practice and the publicly-funded local
chronic disease management programme (Medicare Local). Stakeholders provided
qualitative feedback about the intervention in terms of feasibility,
acceptability and barriers via structured and semi-structured interviews. All
interviews were recorded, transcribed verbatim and analysed using qualitative
thematic analysis to identify key concepts and themes. RESULTS: The study
protocol was abandoned prematurely due to clear lack of feasibility. Of 12
participants, 4 withdrew and none completed pulmonary rehabilitation (PR). The
main reasons for non-participation or study withdrawal related to reluctance to
attend PR (6 of 16) and the burden of increased appointments (4 of 16). PR
conflicted with employment hours, which presented problems for some participants.
Similarly, themes that emerged from qualitative data indicate healthcare provider
perception of deficiencies in funding (for infrastructure and staffing). Health
literacy, motivation, organisation and functional impairment were issues for
patients. CONCLUSIONS: Available data from this small pilot provided valuable
insights to inform future design and implementation strategies. Delivering
structured team-based care to COPD patients presents challenges. In addition to
enhancing health resources for engaging COPD patients, a focus on health literacy
and improving health service access, including colocalisation and access outside
business hours, may be required. TRIAL REGISTRATION: ACTRN12616000342415 ;
16/03/2016.
PMID- 27488413
TI - Isoforms of the Erythropoietin receptor in dopaminergic neurons of the Substantia
Nigra.
AB - Erythropoietin receptor (EpoR) regulates erythrocytes differentiation in blood.
In the brain, EpoR has been shown to protect several neuronal cell types from
cell death, including the A9 dopaminergic neurons (DA) of the Substantia Nigra
(SN). These cells form the nigrostriatal pathway and are devoted to the control
of postural reflexes and voluntary movements. Selective degeneration of A9 DA
neurons leads to Parkinson's disease. By the use of nanoCAGE, a technology that
allows the identification of Transcription Start Sites (TSSs) at a genome-wide
level, we have described the promoter-level expression atlas of mouse A9 DA
neurons purified with Laser Capture Microdissection (LCM). Here, we identify mRNA
variants of the Erythropoietin Receptor (DA-EpoR) transcribed from alternative
TSSs. Experimental validation and full-length cDNA cloning is integrated with
gene expression analysis in the FANTOM5 database. In DA neurons, the EpoR gene
encodes for a N-terminal truncated receptor. Based on STAT5 phosphorylation
assays, we show that the new variant of N-terminally truncated EpoR acts as decoy
when co-expressed with the full-length form. A similar isoform is also found in
human. This work highlights new complexities in the regulation of Erythropoietin
(EPO) signaling in the brain.
PMID- 27488414
TI - The masculinity paradox: facial masculinity and beardedness interact to determine
women's ratings of men's facial attractiveness.
AB - In many species, male secondary sexual traits have evolved via female choice as
they confer indirect (i.e. genetic) benefits or direct benefits such as enhanced
fertility or survival. In humans, the role of men's characteristically masculine
androgen-dependent facial traits in determining men's attractiveness has
presented an enduring paradox in studies of human mate preferences. Male-typical
facial features such as a pronounced brow ridge and a more robust jawline may
signal underlying health, whereas beards may signal men's age and masculine
social dominance. However, masculine faces are judged as more attractive for
short-term relationships over less masculine faces, whereas beards are judged as
more attractive than clean-shaven faces for long-term relationships. Why such
divergent effects occur between preferences for two sexually dimorphic traits
remains unresolved. In this study, we used computer graphic manipulation to morph
male faces varying in facial hair from clean-shaven, light stubble, heavy stubble
and full beards to appear more (+25% and +50%) or less (-25% and -50%) masculine.
Women (N = 8520) were assigned to treatments wherein they rated these stimuli for
physical attractiveness in general, for a short-term liaison or a long-term
relationship. Results showed a significant interaction between beardedness and
masculinity on attractiveness ratings. Masculinized and, to an even greater
extent, feminized faces were less attractive than unmanipulated faces when all
were clean-shaven, and stubble and beards dampened the polarizing effects of
extreme masculinity and femininity. Relationship context also had effects on
ratings, with facial hair enhancing long-term, and not short-term,
attractiveness. Effects of facial masculinization appear to have been due to
small differences in the relative attractiveness of each masculinity level under
the three treatment conditions and not to any change in the order of their
attractiveness. Our findings suggest that beardedness may be attractive when
judging long-term relationships as a signal of intrasexual formidability and the
potential to provide direct benefits to females. More generally, our results hint
at a divergence of signalling function, which may result in a subtle trade-off in
women's preferences, for two highly sexually dimorphic androgen-dependent facial
traits.
PMID- 27488415
TI - Smoking, physical inactivity and obesity as predictors of healthy and disease
free life expectancy between ages 50 and 75: a multicohort study.
AB - BACKGROUND: Smoking, physical inactivity and obesity are modifiable risk factors
for morbidity and mortality. The aim of this study was to examine the extent to
which the co-occurrence of these behaviour-related risk factors predict healthy
life expectancy and chronic disease-free life expectancy in four European cohort
studies. METHODS: Data were drawn from repeated waves of four cohort studies in
England, Finland, France and Sweden. Smoking status, physical inactivity and
obesity (body mass index >=30 kg/m2) were examined separately and in combination.
Health expectancy was estimated by using two health indicators: suboptimal self
rated health and having a chronic disease (cardiovascular disease, cancer,
respiratory disease and diabetes). Multistate life table models were used to
estimate sex-specific healthy life expectancy and chronic disease-free life
expectancy from ages 50 to 75 years. RESULTS: Compared with men and women with at
least two behaviour-related risk factors, those with no behaviour-related risk
factors could expect to live on average8 years longer in good health and 6 years
longer free of chronic diseases between ages 50 and 75. Having any single risk
factor was also associated with reduction in healthy years. No consistent
differences between cohorts were observed. CONCLUSIONS: Data from four European
countries show that persons with individual and co-occurring behaviour-related
risk factors have shorter healthy life expectancy and shorter chronic disease
free life expectancy. Population level reductions in smoking, physical inactivity
and obesity could increase life-years lived in good health.
PMID- 27488416
TI - Using Gini coefficient to determining optimal cluster reporting sizes for spatial
scan statistics.
AB - BACKGROUND: Spatial and space-time scan statistics are widely used in disease
surveillance to identify geographical areas of elevated disease risk and for the
early detection of disease outbreaks. With a scan statistic, a scanning window of
variable location and size moves across the map to evaluate thousands of
overlapping windows as potential clusters, adjusting for the multiple testing.
Almost always, the method will find many very similar overlapping clusters, and
it is not useful to report all of them. This paper proposes to use the Gini
coefficient to help select which of the many overlapping clusters to report.
METHODS: The Gini coefficient provides a quick and intuitive way to evaluate the
degree of the heterogeneity of the collection of clusters, which is useful to
explain how well the cluster collection reveal the underlying true cluster
patterns. Using simulation studies and real cancer mortality data, it is compared
with the traditional approach for reporting non-overlapping clusters. RESULTS:
The Gini coefficient can identify a more refined collection of non-overlapping
clusters to report. For example, it is able to determine when it makes more sense
to report a collection of smaller non-overlapping clusters versus a single large
cluster containing all of them. It also fulfils a set of desirable theoretical
properties, such as being invariant under a uniform multiplication of the
population numbers by the same constant. CONCLUSIONS: The Gini coefficient can be
used to determine which set of non-overlapping clusters to report. It has been
implemented in the free SaTScanTM software version 9.3 ( www.satscan.org ).
PMID- 27488417
TI - Headache-Specific Locus of Control and Migraine-Related Quality of Life:
Understanding the Role of Anxiety.
AB - PURPOSE: This cross-sectional study examined the relationship between headache
specific locus of control (HSLC) and migraine-related quality of life, and
anxiety as a mediator of this relationship. METHOD: Two hundred and thirty-two
people with migraine participated in the treatment of severe migraine trial. At
baseline, participants completed self-report questionnaires of headache-specific
locus of control (HSLC; subscales = internal, chance, and medical professionals),
anxiety, and migraine-related quality of life. Correlations examined
relationships between HSLC, anxiety, and migraine-related quality of life;
ordinary least squares regression evaluated anxiety as a mediator of the
relationship between HSLC and migraine-related quality of life. RESULTS: Higher
internal HSLC was related to higher overall migraine-related quality of life (ps
< .05) and emotion function impairments (p = .012). Anxiety mediated the
relationship between internal HSLC and all measures of migraine-specific quality
of life (ps < .05). Higher external (medical professionals and chance) HSLC was
related to higher migraine-related quality of life impairments (all ps < .001).
CONCLUSION: All HSLC beliefs are associated with higher migraine-related quality
of life impairments. Anxiety mediates the relationship between internal HSLC and
migraine-related quality of life.
PMID- 27488418
TI - Interhospital Transfer of Ruptured AAA's for EVAR: Preposterous or Prudent?
PMID- 27488419
TI - Every Cloud Has a Silver Lining: Proneurogenic Effects of Abeta Oligomers and
HMGB-1 via Activation of the RAGE-NF-kappaB Axis.
AB - BACKGROUND & OBJECTIVE: Since its initial discovery, current understanding on the
functional role of the Receptor for Advanced Glycation End-products (RAGE) in
physiology and in pathology has impressively grown, especially in consideration
of its large ligand repertoire (AGEs, HMGB-1, beta amyloid, S100B/S100A12) and
its potential involvement in the pathophysiology of several chronic human
disorders. Downstream RAGE engagement by its ligands, NF-kappaB signaling
activation has been demonstrated in several cell phenotypes, including neurons
and glia. Based on the observation that in Alzheimer's Disease (AD) brain
expression of RAGE and its ligands is upregulated and that RAGE/NF-kappaB axis
activation can trigger an autoregulatory loop which further amplifies
neuroinflammation and neurodegeneration, this signaling pathway has been
hypothesized to greatly contribute to AD pathophysiology. Herein we review the
vast array of information supporting a detrimental role of RAGE/NF-kappaB axis
activation in AD brain and discuss those data in the context of recent findings
obtained in our laboratory pointing to an unexpected effect elicited by this
signaling pathway which may rather contribute to reparative mechanisms in AD,
namely positive modulation of adult neurogenesis. Interestingly, the
proneurogenic effect resulting from RAGE/NF-kappaB axis activation could be
induced by molecules which are commonly considered as mediators of toxicity, like
Abeta oligomers and HMGB-1. CONCLUSION: Altogether, despite a large set of data
suggesting that RAGE may represent an interesting target for the pharmacological
treatment of AD, the complex functional roles of the receptor would require the
use of molecules able to counteract RAGE negative effects without altering the
positive ones such as the promotion of adult neurogenesis.
PMID- 27488420
TI - Comparable Neuroprotective Effects of Pergolide and Pramipexole on Ferrous
Sulfate-Induced Dopaminergic Cell Death in Cell Culture.
AB - BACKGROUND: Dopamine agonists are utilized clinically as an initial treatment in
younger Parkinson's disease patients to delay the side effects associated with
commencement of levodopa medication. These agonists also serveas adjunctive
therapeutics with levodopa to lower the incidence of adverse motor symptoms in
advanced stages of the disease. OBJECTIVES: To compare the neuroprotective
effects of the dopamine agonists pergolide and pramipexole on ferrous sulfate
induced neurotoxicity in dopaminergic neurons from primary mesencephalic cell
culture. METHODS: Pergolide (0.001-1 MUM) and pramipexole (0.01-200 MUM) were
administered to 8 day primary murine mesencephalic cultures for 24 h. in the
presence or absence of desferal, sulpiride or cycloheximide. Ferrous sulfate (450
MUM) was then added for 24 hrs. Lactate dehydrogenase was assayed in the
supernatant, glutathione concentrations measured in cell lysates and fixed cells
were stained for tyrosine hydroxylase. RESULTS: Ferrous sulphate induced
neurotoxity in cultures (p<0.0001) was abolished in the presence of the iron
chelator desferal (p<0.008). Both pergolide (p<0.0001) and pramipexole (p<0.0001)
significantly protected dopaminergic neurons against ferrous sulfate induced
neurotoxicity and pramipexole helped preserve neurite morphology. Pramipexole
treatment significantly reduced lactate dehydrogenase release (p<0.0001) as a
measure of cellular injury. The dopamine receptor antagonist sulpiride (p<0.0001)
and the protein synthesis inhibitor cycloheximide (p<0.0001) reduced the
neuroprotective effects of pergolide indicating the involvement receptor
stimulation and de novo protein synthesis in pergolide-mediated neuroprotection.
Pramipexole also significantly reversed the decrease in cellular glutathione
concentrations induced by ferrous sulfate (p<0.001). CONCLUSION: Both pergolide
and pramipexole protect dopaminergic neurons against the neurotoxicity of ferrous
sulfate. Pergolide specifically protects dopaminergic neurons through activation
of dopamine receptors and de novo protein synthesis whereas pramipexole shows an
overall effect through an antioxidant mechanism.
PMID- 27488421
TI - Nanomaterials for Neurology: State-of-the-Art.
AB - Despite the numerous challenges associated with the application of nanotechnology
in neuroscience, it promises to have a significant impact on our understanding of
how the nervous system works, how it fails in disease, and the development of
earlier and less-invasive diagnostic procedures so we can intervene in the pre
clinical stage of neurological disease before extensive neurological damage has
taken place. Ultimately, both the challenges and opportunities that
nanotechnology presents stem from the fact that this technology provides a way to
interact with neural cells at the molecular level. In this review we provide a
neurobiological overview of key neurological disorders, describe the different
types of nanomaterials in use and discuss their current and potential uses in
neuroscience. We also discuss the issue of toxicity in these nanomaterials. This
review presents many of the different applications that advances in
nanotechnology are having in the field of neurological sciences, especially the
high impact they are having in the development of new treatment modalities for
neurological disorders that will induce the expected physiological response while
minimizing undesirable secondary effects. In conclusion, we weigh in on what the
promises and challenges are for future development in this groundbreaking field.
PMID- 27488422
TI - Lithium Restores Age-related Olfactory Impairment in the Ts65Dn Mouse Model of
Down Syndrome.
AB - BACKGROUND & OBJECTIVE: Down syndrome, a genetic condition caused by triplication
of chromosome 21, is characterized by widespread neurogenesis reduction and
cognitive impairment. Unlike other brain functions, smell is not impaired at
early life stages and olfactory deterioration begins to appear in adulthood.
Similarly to individuals with Down syndrome, in the Ts65Dn mouse model of Down
syndrome smell function is normal at early life stages. Smell impairment only
appears in adulthood associated with a reduction in the number of new granule
neurons migrated to the olfactory bulb from the subventricular zone. Based on
evidence that lithium positively impacts neurogenesis, the goal of current study
was to establish whether treatment with lithium restores olfactory bulb
neurogenesis and olfactory performance in middle-aged Ts65Dn mice. METHOD:
Euploid and Ts65Dn mice aged 13 months were treated with lithium chow or control
chow for one month. Before the end of treatment, mice were injected with BrdU, in
order to label proliferating cells. Results showed that in Ts65Dn mice lithium
treatment restored the number of neural precursor cells in the subventricular
zone of the lateral ventricle, rostral migratory stream and olfactory bulb. This
effect was accompanied by restoration of olfactory performance. Unlike in
olfactory neurogenic regions, treatment had no neurogenesis-enhancing effect on
the subgranular zone of the hippocampal dentate gyrus, indicating that lithium
has no generalized positive effect on the brain. CONCLUSION: Results suggest that
lithium may have a positive impact in brain disorders that, similarly to Down
syndrome, are characterized by olfactory decline and neurogenesis impairment in
the subventricular zone.
PMID- 27488424
TI - Abstracts from the International Surgical Congress of the Association of Surgeons
of Great Britain and Ireland, Belfast, 2016.
PMID- 27488423
TI - Metabotropic Glutamate Receptor 7 (mGluR7) as a Target for Modulating Pain-evoked
Activities of Neurons in the Hippocampal CA3 Region of Rats.
AB - BACKGROUND: Metabotropic glutamate could contribute to the development of
neuropathic pain-related behaviors. Previously, we have confirmed that the
glutamic acid and dizocilpine maleate in the hippocampal CA3 region are involved
in the modulation of noxious stimulation. However, whether the metabotropic
glutamate receptor 7 (mGluR7) can modulate the pain-evoked electrical activities
of pain-excited neurons and pain-inhibited neurons in the hippocampal CA3 region
is not clear. OBJECTIVE: The study aimed to examine the effects of mGluR7
allosteric agonist N,N'-dibenzhydrylethane- 1,2-diamine dihydrochloride (AMN082)
and antagonist 6-(4-methoxyphenyl)-5-methyl-3- pyridin-4-ylisoxazolo[4,5
c]pyridin-4(5H)-one (MMPIP) on the pain-evoked electrical activities of pain
excited neurons and pain-inhibited neurons in the CA3 region of rats. METHOD: A
train of electric impulses applied to the sciatic nerve were used for noxious
stimulation. The bio-electrical activities of pain-excited neuron or pain
inhibited neuron in the CA3 region were recorded by a glass microelectrode.
RESULTS: Our results exhibited that intra-CA3 region administration of the
glutamic acid or AMN082 increased the pain-evoked discharged frequency and
shortened the latency of pain-excited neuron, while decreased the pain-evoked
discharged frequency and prolonged the inhibitory duration of paininhibited
neuron in the CA3 region. The intra-CA3 region microinjection of MMPIP produced
the opposite response. CONCLUSION: These findings demonstrated that the glutamic
acid and mGluR7 in hippocampal CA3 region are involved in the modulation of
nociceptive information transmission by regulating pain-evoked electric
activities of pain-excited neurons and pain-inhibited neurons.
PMID- 27488426
TI - Asymmetry-induced resistive switching in Ag-Ag2S-Ag memristors enabling a
simplified atomic-scale memory design.
AB - Prevailing models of resistive switching arising from electrochemical formation
of conducting filaments across solid state ionic conductors commonly attribute
the observed polarity of the voltage-biased switching to the sequence of the
active and inert electrodes confining the resistive switching memory cell. Here
we demonstrate stable switching behaviour in metallic Ag-Ag2S-Ag nanojunctions at
room temperature exhibiting similar characteristics. Our experimental results and
numerical simulations reveal that the polarity of the switchings is solely
determined by the geometrical asymmetry of the electrode surfaces. By the
lithographical design of a proof of principle device we demonstrate the merits of
simplified fabrication of atomic-scale, robust planar Ag2S memory cells.
PMID- 27488425
TI - Mood, anxiety, and alcohol use disorders and later cause-specific sick leave in
young adult employees.
AB - BACKGROUND: Mental disorders strongly influence work capability in young adults,
but it is not clear which disorders that are most strongly associated with sick
leave, and which diagnoses that are stated on the sick leave certificates. Better
knowledge of the impairments associated with different mental disorders is needed
for optimal planning of interventions and prioritization of health services. In
the current study, we investigate the prospective associations between eight
mood, anxiety, and alcohol use disorders, and later sick leave granted for
mental, somatic, or any disorder. METHODS: Lifetime mental disorders were
assessed by structured diagnostic interviews in 2,178 young adults followed for
eight years with registry data on sick leave. Relative risk ratios were estimated
for the associations between each mental disorder and the different forms of sick
leave. RESULTS: All included diagnoses were associated with later sick leave. In
adjusted analyses, major depressive disorder and generalized anxiety disorder
were the strongest predictors of sick leave granted for mental disorders, whereas
social anxiety disorder and specific phobia were the strongest predictors of sick
leave granted for somatic disorders. Specific phobia and major depressive
disorder had the highest attributable fractions for all-cause sick leave.
CONCLUSIONS: Mood and anxiety disorders constituted independent risk factors for
all cause sick leave, whereas alcohol use disorders seemed to be of less
importance in young adulthood. Disorders characterised by distress were most
strongly associated with sick leave granted for mental disorders, whereas
disorders characterised by fear primarily predicted sick leave granted for
somatic conditions. A large part of all sick leave is related to specific phobia,
due to the high prevalence of this disorder. The impairment associated with this
common disorder may be under-acknowledged, and it could decrease work capacity
among individuals with somatic disorders. This disorder has good treatment
response and may be overlooked as a target for interventions aimed at prevention
of sick leave.
PMID- 27488427
TI - 68Ga-PSMA PET/MR Showing Intense PSMA Uptake in Nodular Fasciitis Mimicking
Prostate Cancer Metastasis.
AB - The recently introduced PSMA PET has developed as a powerful imaging tool for
staging of prostate cancer. This case showed an intense uptake of Ga-PSMA in a
soft-tissue mass of the rectus femoris muscle. Histopathology revealed the
diagnosis of fasciitis nodularis. Therefore, it advises caution particularly in
patients with solitary and atypical located lesions as they might not be
indicative for metastatic prostate cancer, but eventually be caused by different
conditions.
PMID- 27488429
TI - Reverse Mismatch Pattern in Cardiac 18F-FDG Viability PET/CT Is Not Associated
With Poor Outcome of Revascularization: A Retrospective Outcome Study of 91
Patients With Heart Failure.
AB - PURPOSE: Revascularization strategies in patients with ischemic heart failure
(HF) should be based on evidence of reversible perfusion defects and myocardial
viability. Myocardial viability assessment is preferably based on dual isotope
PET using perfusion and metabolism tracers. However, in a nonnegligible subset of
HF patients, reverse mismatch (RM) pattern (reduced glucose uptake relative to
perfusion) of unknown origin is observed. We aimed to investigate determinants of
RM and the impact of RM on the subsequent improvement in left ventricular
function by revascularization. PATIENTS AND METHODS: Ninety-one patients (12
women, 25 with diabetes) with HF undergoing Rb perfusion PET and hyperinsulinemic
euglycemic clamp F-FDG viability PET were retrospectively reviewed. RESULTS:
Follow-up time was 12 to 33 months. In 30 of 91 patients, hypometabolic
myocardium exceeded the percentage of hypoperfused myocardium; however, only in
12 of 91 patients was the RM considered significant (percentage RM in the left
ventricle, 42.5 +/- 12.9 [reverse patients] vs 14.1 +/- 8.6 [scar and hibernation
patients]; P < 0.001). Diabetes status per se did not predict RM, but a
significant inverse correlation between insulin sensitivity and RM was observed.
The frequency of hospitalization, cardiac death, and myocardial infarctions were
not significantly higher in RM patients. Reverse mismatch patients benefited from
revascularization to the same extent as patient with normal metabolic patterns.
CONCLUSIONS: Reverse mismatch is common among HF patients (~15%) and is inversely
correlated to insulin sensitivity. It is not, however, associated with increased
cardiac morbidity and mortality and does not predict a worse outcome after
revascularization.
PMID- 27488430
TI - Pitfalls in the Performance and Interpretation of Scintigraphic Imaging for
Pleuroperitoneal Shunt.
AB - Ascites can cause pleural effusions when the peritoneal fluid crosses the
diaphragm through a pleuroperitoneal shunt in the setting of hepatic cirrhosis
(hepatic hydrothorax) or malignant ascites. Scintigraphic imaging for
pleuroperitoneal shunt requires intraperitoneal injection of Tc-SC or Tc
macroaggregated albumin followed by planar imaging of the chest and abdomen.
Pleuroperitoneal shunt is confirmed by identifying radiotracer crossing the
diaphragm from the peritoneal to pleural space. An atlas of pleuroperitoneal
shunt imaging pitfalls is presented to facilitate optimal performance and
interpretation of nuclear pleuroperitoneal shunt examinations. Examples include
cases of nondiagnostic radiotracer injections, processing errors, and nontarget
uptake.
PMID- 27488431
TI - 123I-FP-CIT-SPECT in Encephalitis Involving Substantia Nigra.
AB - I-FP-CIT-SPECT is currently used to detect functional impairment of striatal
structures. We report herein a case where I-FP-CIT abnormalities are seemingly
related to an encephalitis involving substantia nigra. A few months after a
documented encephalitis, a 19-year-old woman experienced a Parkinsonism with a
right dominance. There was a reduction in the striatal binding of I-FP-CIT,
especially on the left side, in accordance with the right dominance of the
Parkinsonism.
PMID- 27488432
TI - Intense 99mTc-MDP and 18F-NaF Activity in Long-standing Subcutaneous Implants.
AB - A 64-year-old woman with a newly diagnosed left breast cancer underwent a
presurgical Tc-MDP whole-body imaging, which showed 1 intense activity in the
midline upper abdomen and another overlapping the upper thoracic spine. An F-NaF
PET/CT scan performed a day later also revealed the elevated activity in the same
regions. The activity corresponded to calcified subcutaneous implants, which were
placed there more than 30 years ago.
PMID- 27488434
TI - Investigating the risk factors of vestibular dysfunction and the relationship
with presbyacusis in Singapore.
AB - OBJECTIVES: This study aimed to determine the prevalence of vestibular
dysfunction in the Singaporean elderly and its association with presbyacusis, age
and other associated risk factors. METHODS: A cross-sectional study was
undertaken in a tertiary otorhinolaryngology department and the community.
Healthy adults aged 40 years and above who participated in the institution's
community presbyacusis screening programme were invited to participate. The main
outcome measures including pure tone audiometry and vestibular assessment were
obtained using a modified Clinical Test of Sensory Interaction on Balance.
RESULTS: The prevalence of vestibular dysfunction and presbyacusis in the study
population of 216 participants was 30.1 per cent (95 per cent confidence
interval, 24.0 to 36.2 per cent) and 55.6 per cent (95 per cent confidence
interval, 49.0 to 62.2 per cent), respectively. The median age was 60 years
(range, 40-86 years). The adjusted odds ratio for vestibular dysfunction
increased by 6.2 per cent with every year of life (p 0.05). CONCLUSION:
Vestibular dysfunction is independently associated with ageing and presbyacusis.
Further research into the benefits of additional screening for vestibular
dysfunction in elderly presbyacusis patients is warranted.
PMID- 27488433
TI - Interaction between synaptic inhibition and glial-potassium dynamics leads to
diverse seizure transition modes in biophysical models of human focal seizures.
AB - How focal seizures initiate and evolve in human neocortex remains a fundamental
problem in neuroscience. Here, we use biophysical neuronal network models of
neocortical patches to study how the interaction between inhibition and
extracellular potassium ([K (+)] o ) dynamics may contribute to different types
of focal seizures. Three main types of propagated focal seizures observed in
recent intracortical microelectrode recordings in humans were modelled: seizures
characterized by sustained (~30-60 Hz) gamma local field potential (LFP)
oscillations; seizures where the onset in the propagated site consisted of LFP
spikes that later evolved into rhythmic (~2-3 Hz) spike-wave complexes (SWCs);
and seizures where a brief stage of low-amplitude fast-oscillation (~10-20 Hz)
LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction
between elevated [K (+)] o (due to abnormal potassium buffering by glial cells)
and the strength of synaptic inhibition plays a predominant role in shaping these
three types of seizures. (2) Strengthening of inhibition leads to the onset of
sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained
either by the weakening of inhibitory synapses, or by a transient strengthening
followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or
breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases
their spiking activity and leads them eventually into depolarization block. Ictal
spike-wave discharges in the model are then sustained solely by pyramidal
neurons. (4) FS cell dynamics are also critical for seizures where the evolution
into SWC activity is preceded by low-amplitude fast oscillations. Different
levels of elevated [K (+)] o were important for transitions into and maintenance
of sustained gamma oscillations and SWC discharges. Overall, our modelling study
predicts that the interaction between inhibitory interneurons and [K (+)] o glial
buffering under abnormal conditions may explain different types of ictal
transitions and dynamics during propagated seizures in human focal epilepsy.
PMID- 27488435
TI - Vaccine hesitancy among general practitioners: evaluation and comparison of their
immunisation practice for themselves, their patients and their children.
AB - To gain knowledge about vaccine hesitancy among general practitioners (GPs), we
conducted a survey to compare their vaccination attitudes for themselves, their
children and their patients. A questionnaire survey was sent to GPs working in
private practice in the Rhone-Alpes region, France, between October 2013 and
January 2014. GPs' immunisation practices for diphtheria-tetanus-poliomyelitis
(DTP), measles-mumps-rubella (MMR), pneumococcal, pertussis, hepatitis B (hepB),
human papillomavirus (HPV), seasonal and H1N1 influenza and meningococcal C
(menC) vaccines were considered. Divergence was defined by the presence of at
least one different immunisation practice between their patients and their
children. A total of 693 GPs answered the questionnaire. When considering all
investigated vaccines, 45.7 % of divergence was found. Individually, divergence
was highest for the newest and more controversial, i.e. HPV (11.8 %), hepB (13.1
%), menC (23.7 %) and pneumococcal (19.8 %) vaccines. Only 73.9 % of GPs declared
that they recommended HPV vaccine for their daughters. After multivariate
analysis, older age was associated with higher risk of divergence. According to
the French 2012 recommendations, GPs were insufficiently immunised, with 88 % for
DTP and 72 % for pertussis. GPs declared to recommend vaccination against DTP,
pertussis and MMR for their patients and their children in more than 95 % of
cases. The declared rates of recommendation were lower than 90 % for other
vaccines. These results bring new insight about vaccine hesitancy. GPs have
divergent immunisation attitudes toward their relatives and their patients,
especially when considering the newest and most controversial vaccines, with HPV
vaccine being the main focus of controversies.
PMID- 27488436
TI - Change of annexin binding of monocytes as an expression of cellular response to
Candida albicans: down-regulation in severe sepsis.
AB - To study the differences of monocyte activation by albicans and non-albicans
species of Candida and its change in sepsis, peripheral blood mononuclear cells
were isolated from 17 healthy volunteers and 26 patients with severe
sepsis/shock, and incubated in the absence/presence of heat-killed (HK) isolates
of four different Candida species and purified beta-D-glucan from C.albicans.
Experiments were repeated in the presence and absence of inhibitors of
intracellular activation pathways. Expression of annexin V on cells membranes of
monocytes and lymphocytes, cytoplasmic activity of caspase-3, and DNA
fragmentation of monocytes were studied. Membrane expression of annexin V on
viable monocytes of healthy volunteers decreased significantly after incubation
with C.albicans but not with non-albicans species. The decrease was dose
dependent from the Candida inoculum and by the concentration of beta-D-glucan. A
relationship with inhibition of apoptosis was found as the activity of caspase-3
activity, and the level of DNA fragmentation were also decreased. Incubation in
the absence/presence of inhibitors showed that the decrease by annexin V
expression resulted by activation of the dectin-1 pathway and Raf-1 by beta-D
glucan. The decrease of annexin V(+)/PI(-) expression was not shown on monocytes
of patients with severe sepsis/shock, where no effect of inhibitors was found.
Decrease of annexin V binding on monocytes can be viewed as a selective response
to C.albicans partly effected through activation of dectin-1. This response is
down-regulated after a septic insult.
PMID- 27488437
TI - Success of benznidazole chemotherapy in chronic Trypanosoma cruzi-infected
patients with a sustained negative PCR result.
AB - Cure assessment in chronic Trypanosoma cruzi infection is controversial, mainly
because of the lack of reliable tests to ensure parasite elimination. Here, we
assess the impact of benznidazole therapy on the conventional serology and
parasitaemia in chronic Chagas disease. A total of 455 patients with long-term
Trypanosoma cruzi infection underwent specific chemotherapy with benznidazole.
Their parasitological status was assessed by polymerase chain reaction (PCR)
detection of T. cruzi DNA. Drops in the titres of antibody levels were serially
measured by indirect immunofluorescence assay (IFI) and chemiluminescent
microparticle immunoassay (CMIA). Patients were monitored during the treatment
period and for a further 90, 150 and 240 days. Controls were repeated yearly
during the 7-year follow-up. The PCR result was negative in all patients between
60-day (n = 22) and 90-day (n = 294) controls. Treatment failure was detected in
45 patients and was significantly more frequent in those who did not complete the
therapy [12 out of 13 (92 %) vs. 33 out of 442 (7 %)] (p = 0.0001). A significant
drop in serum titres was detected after the first follow-up year in patients with
sustained negative PCR results: 2nd year (p = 0.029 by IFI; p = 0.002 by CMIA),
5th year (p = 0.036 by IFI; p = 0.039 by CMIA) and 6th year (p = 0.028 by IFI; p
= 0.019 by CMIA). The results point to a beneficial effect of benznidazole and
may be the cure of chronic patients who had a consistently negative PCR result
throughout the follow-up period.
PMID- 27488438
TI - Klebsiella pneumoniae bloodstream infection, antimicrobial resistance and
consumption trends in Ireland: 2008 to 2013.
AB - This study aimed to describe the epidemiology and antimicrobial resistance trends
of Klebsiella pneumoniae bloodstream infection (BSI) in Ireland, in conjunction
with national antimicrobial consumption data, during the period 2008 to 2013. A
retrospective cohort study of K. pneumoniae BSI cases was conducted, based on
notifications from Irish microbiology laboratories to the Health Protection
Surveillance Centre (HPSC). In total, 1942 K. pneumoniae BSI cases were
identified over 6 years, with 310 reported in 2008 and 326 reported in 2013. From
2008 to 2013, the proportion of isolates resistant to co-amoxiclav (24 % versus
29 %), piperacillin-tazobactam (11 % versus 27 %), third generation
cephalosporins (3GC) (11 % versus 21 %), fluoroquinolones (13 % versus 21 %) and
gentamicin (11 % versus 17 %) increased overall, concurrent with increasing
national rates of antimicrobial consumption in Ireland (acute hospitals: 35.87
versus 39.77 defined daily doses (DDD) per 100 bed days used (BDU); and
community: 6.38 versus 7.85 DDD per 1000 inhabitants per day (DID)). Enhanced
data on the patient's admission route was available for 735 (38 %) cases.
Overall, 51 % (n = 378) were categorised as 'acquired in the reporting hospital'.
The all-cause mortality was 20 %, with 115 deaths, 101 (88 %) of whom died within
30 days of blood culture sampling date. K. pneumoniae is the second most common
cause of Gram-negative BSI in Ireland, with most cases healthcare-associated and
an all-cause mortality of 20 % reported in this study. Annual increases in
resistance to different antimicrobial classes and in a multi-drug resistant
phenotype have been observed, concurrent with increasing national broad spectrum
antimicrobial consumption. These trends portend a risk to patient outcomes and
highlight the urgency for individual prescribers to evaluate their antimicrobial
prescribing habits in hospitals, long-term care and community settings.
PMID- 27488439
TI - Co-stimulatory CD28 and transcription factor NFKB1 gene variants affect
idiopathic recurrent miscarriages.
AB - Co-stimulatory CD28 and transcription factor NFKB1 genes are considered as a
crucial player in the determination of inflammatory responses; genetic
variability in these may modulate the risk for idiopathic recurrent miscarriages
(IRM). We investigated the association of functional variants of CD28 (rs3116496
T/C) and NFKB1 (rs28362491 ins/del and rs696 A/G) with IRM cases. We recruited
200 IRM women with a history of at least three consecutive pregnancy losses
before 20th week of pregnancy and 300 fertile control women. Determination of
CD28 (rs3116496 T/C) and NFKB1 (rs28362491 ins/del and rs696 A/G) gene variants
were based on the polymerase chain reaction pursued by restriction fragment
length polymorphism analysis and validated with Sanger sequencing. Single marker
analysis and multifactor dimensionality reduction (MDR) model used to predict the
IRM risk. We observed nearly three- to twofold increased risk in single marker
analysis for minor homozygous genotypes of rs3116496 T/C, rs28362491 ins/del and
rs696 A/G tag-SNPs in IRM cases, suggesting the risk association. In MDR
analysis, we observed 10.5-fold augmented risk among IRM women in three-SNP model
(rs3116496 T/C, rs28362491 ins/del and rs696 A/G). The eQTL mapping analyses was
performed to strengthen the results of our study. The eQTL mapping analysis
revealed that the variations in CD28 and NFKB1 gene content might affect the
abundance of transcripts of CD28 and Family with sequence similarity 177 member
A1 (FAM177A1) genes, respectively. These results suggest that CD28 and NFKB1 gene
variants may be associated with increased risks to IRM.
PMID- 27488440
TI - Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with
idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that
is refractory to treatment and carries a high mortality rate. IPF is frequently
associated with lung cancer. Identification of molecular targets involved in both
diseases may elucidate novel molecular mechanisms contributing to their
pathology. Recent studies of microRNA (miRNA) expression signatures showed that
microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this
study was to investigate the functional significance of miR-29a in lung cancer
cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular
targets modulated by miR-29a in these cells. We confirmed the downregulation of
miR-29a in clinical specimens of IPF and lung cancer. Restoration of miR-29a
suppressed cancer cell aggressiveness and fibroblast migration. A combination of
gene expression data and in silico analysis showed that a total of 24 genes were
putative targets of miR-29a. Among them, lysyl oxidase-like 2 (LOXL2) and serpin
peptidase inhibitor clade H, member 1 (SERPINH1) were direct targets of miR-29a
by luciferase reporter assays. The functions of LOXL2 and SERPINH1 contribute
significantly to collagen biosynthesis. Overexpression of LOXL2 and SERPINH1 was
observed in clinical specimens of lung cancer and fibrotic lesions.
Downregulation of miR-29a caused overexpression of LOXL2 and SERPINH1 in lung
cancer and IPF, suggesting that these genes are involved in the pathogenesis of
these two diseases.
PMID- 27488443
TI - Whole-gene CFTR sequencing combined with digital RT-PCR improves genetic
diagnosis of cystic fibrosis.
AB - Despite extensive screening, 1-5% of cystic fibrosis (CF) patients lack a
definite molecular diagnosis. Next-generation sequencing (NGS) is making
affordable genetic testing based on the identification of variants in extended
genomic regions. In this frame, we analyzed 23 CF patients and one carrier by
whole-gene CFTR resequencing: 4 were previously characterized and served as
controls; 17 were cases lacking a complete diagnosis after a full conventional
CFTR screening; 3 were consecutive subjects referring to our centers, not
previously submitted to any screening. We also included in the custom NGS design
the coding portions of the SCNN1A, SCNN1B and SCNN1G genes, encoding the subunits
of the sodium channel ENaC, which were found to be mutated in CF-like patients.
Besides 2 novel SCNN1B missense mutations, we identified 22 previously-known CFTR
mutations, including 2 large deletions (whose breakpoints were precisely mapped),
and novel deep-intronic variants, whose role on splicing was excluded by ex-vivo
analyses. Finally, for 2 patients, compound heterozygotes for a CFTR mutation and
the intron-9c.1210-34TG[11-12]T5 allele-known to be associated with decreased
CFTR mRNA levels-the molecular diagnosis was implemented by measuring the
residual level of wild-type transcript by digital reverse transcription
polymerase chain reaction performed on RNA extracted from nasal brushing.
PMID- 27488444
TI - Obesity and urolithiasis: evidence of regional influences.
AB - There is evidence that obese patients have an increased risk of renal stone
formation, although this relationship could be less evident in some populations.
The aim of this study was to evaluate the impact of overweight and obesity on the
risk of renal stone formation in a population consuming a Mediterranean diet and
to better elucidate the mechanisms underlying the increased risk of urolithiasis
observed in obese subjects. We performed a retrospective review of 1698 stone
forming patients (mean age 45.9 +/- 14.6 years; 984/714 M/F), attending
outpatient stone clinics in Milan and Florence, seen between January 1986 and
June 2014. Records were reviewed and data collected pertaining to age, gender,
weight, height, stone composition, association with diabetes type 2 or gout and
metabolic profile of 24-h urine to perform a descriptive study. We estimated
prevalence ratios for body mass index (BMI) categories (underweight: BMI <18.5,
normal: BMI 18.5-24.9, overweight: BMI 25-29.9 and obese >=30). Overweight and
obesity were present in 40.7 and 8 % of the men and in 19.9 and 8.7 % of the
women in the study population. The mean BMI of patients with urolithiasis was
found to be 24.5 +/- 7.5 kg/m2. BMI values were positively correlated with age (p
= 0.000) and mean BMI was higher in males than in females (25.5 +/- 8.9 vs 23.2
+/- 4.4 kg/m2). In males, rates of overweight and obesity in renal stone formers
were higher than the rates reported in the Italian general population in 2004
only for the age group 25-44 years, whereas males in all the other age groups and
in females the rates of overweight and obesity in renal stone formers were
similar to rates reported in the Italian general population. The rates of
overweight and obesity were significantly different in patients with different
chemical stone composition. In particular, patients with uric acid stones have
rates of overweight and obesity higher than patients with calcium stones or other
types of calculi. Also the rates of type 2 diabetes and gout were greater in
patients with overweight and obesity. In overweight and obese patients, the
urinary excretion of risk factors for stone formation, such as calcium, oxalate
and urate, and also of inhibitory substances, such as citrate, were significantly
higher than in patients with normal weight or underweight. The prevalence of
overweight and obesity in patients with urinary calculi from a country consuming
a Mediterranean diet is not higher than in the general population. It should be
taken into account that not all the dietary patterns that are associated with
obesity may involve a parallel increase in the risk of forming kidney stones and
that epidemiological findings from one country could not be confirmed in other
countries with different climatic, socioeconomic and cultural features.
PMID- 27488445
TI - [Kurt Seidel (1914-1990) : Between medicine and politics].
AB - Prof. Dr. med. Kurt Seidel played an outstanding role in the post-war history of
rheumatology in eastern Germany. This is documented by the textbook articles and
review articles written by him, by the foundation and leadership over many years
of the working and research group of rheumatology in Jena, by his role in the
formation of the divided society of the German Democratic Republic (GDR) and by
the preparation of its chronical in 1984. An appreciation of his achievements
against the background of the scientific political circumstances prevailing at
that time is documented through a dissertation.
PMID- 27488442
TI - Functional RNAs control T follicular helper cells.
AB - T follicular helper cells (Tfh cells), which are a prototypic subset of effector
CD4+ T cells, regulate the production of high-affinity antibodies by controlling
B cells at initial and recall phases. Since the discovery of Tfh cells in human
tonsils, many notable studies focusing on Tfh cells have clarified mechanisms
underlying Tfh-cell-related physiological and pathological settings. Results of
these studies revealed a chief regulatory function of BCL6 in Tfh cells and the
involvement of Tfh cells in the pathogenesis of various disorders including
autoimmune diseases, allergies and cancers. Further, accumulating evidence has
revealed microRNAs (miRNAs) of functional noncoding RNAs (ncRNAs) to be cardinal
regulators of Tfh cells during the processes of development, differentiation and
plasticity. In this review article, we summarize and discuss the results of
recent studies about miRNAs operating Tfh-cell function and their relationships
in diseases. Through the window of such functional ncRNAs, the functional
significance of Tfh cells in CD4+ T-cell biology is becoming apparent. Studies to
determine the complex background of the genetic program of Tfh cells operated by
functional RNAs should lead to an understanding of the manifestations of Tfh
cells with unidentified pathophysiological relevance.
PMID- 27488441
TI - MicroRNAs in non-small cell lung cancer and idiopathic pulmonary fibrosis.
AB - In spite of advances in the diagnosis and current molecular target therapies of
lung cancer, this disease remains the most common cause of cancer-related death
worldwide. Approximately 80% of lung cancers is non-small cell lung cancer
(NSCLC), and 5-year survival rate of the disease is ~20%. On the other hand,
idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung
disease of unknown etiology. IPF is refractory to treatment and has a very low
survival rate. Moreover, IPF is frequently associated with lung cancer. However,
the common mechanisms shared by these two diseases remain poorly understood. In
the post-genome sequence era, the discovery of noncoding RNAs, particularly
microRNAs (miRNAs), has had a major impact on most biomedical fields, and these
small molecules have been shown to contribute to the pathogenesis of NSCLC and
IPF. Investigation of novel RNA networks mediated by miRNAs has improved our
understanding of the molecular mechanisms of these diseases. This review
summarizes our current knowledge on aberrantly expressed miRNAs regulating NSCLC
and IPF based on miRNA expression signatures.
PMID- 27488446
TI - [Diagnostics and treatment of polymyalgia rheumatica].
AB - Polymyalgia rheumatica (PMR) is the most common autoimmune inflammatory disease
in older persons with an average age of onset of 73 years. Typical symptoms
include acute or subacute bilateral shoulder pain with severe stiffness and often
neck and bilateral hip pain. Giant cell arteritis (GCA) occurs in approximately
20 % of cases and up to two thirds of patients with GCA have symptoms of PMR.
There are many disease which mimic PMR, elderly onset rheumatoid arthritis is
frequently misdiagnosed as PMR. Although there are no specific laboratory tests,
C-reactive protein and erythrocyte sedimentation rates are elevated in over 90 %
of patients. The diagnosis may be aided by imaging, especially ultrasonography
and magnetic resonance imaging (MRI). Treatment currently consists of
glucocorticoids at an initial dose of 12.5-25 mg prednisone equivalent daily.
Treatment duration is typically 2-3 years but may be longer. Under certain
conditions low-dose methotrexate can be used as adjuvant therapy.
PMID- 27488447
TI - [Treat-to-target (T2T) recommendation for patients with spondyloarthritis -
translation into German].
AB - The management of patients with spondyloarthritis (SpA) has experienced a
paradigm shift in recent years. This is true for the treatment of axial as well
as peripheral manifestations. International treat to target (T2T) recommendations
for SpA based on the T2T strategy have now also been published, which contain 5
higher level principles (A-E) in addition to the 15 recommendations. In order to
make the recommendations known and to promote national distribution, German
experts have now issued a translation of the T2T recommendations for SpA into
German.
PMID- 27488448
TI - Repeated eye reduction events reveal multiple pathways to degeneration in a
family of marine snails.
AB - Eye reduction occurs in many troglobitic, fossorial, and deep-sea animals but
there is no clear consensus on its evolutionary mechanism. Given the highly
conserved and pleiotropic nature of many genes instrumental to eye development,
degeneration might be expected to follow consistent evolutionary trajectories in
closely related animals. We tested this in a comparative study of ocular anatomy
in solariellid snails from deep and shallow marine habitats using morphological,
histological, and tomographic techniques, contextualized phylogenetically. Of 67
species studied, 15 lack retinal pigmentation and at least seven have eyes
enveloped by surrounding epithelium. Independent instances of reduction follow
numerous different morphological trajectories. We estimate eye loss has evolved
at least seven times within Solariellidae, in at least three different ways:
characters such as pigmentation loss, obstruction of eye aperture, and "lens"
degeneration can occur in any order. In one instance, two morphologically
distinct reduction pathways appear within a single genus, Bathymophila. Even
amongst closely related animals living at similar depths and presumably with
similar selective pressures, the processes leading to eye loss have more
evolutionary plasticity than previously realized. Although there is selective
pressure driving eye reduction, it is clearly not morphologically or
developmentally constrained as has been suggested by previous studies.
PMID- 27488449
TI - A decision analytic model to investigate the cost-effectiveness of poisoning
prevention practices in households with young children.
AB - BACKGROUND: Systematic reviews and a network meta-analysis show home safety
education with or without the provision of safety equipment is effective in
promoting poison prevention behaviours in households with children. This paper
compares the cost-effectiveness of home safety interventions to promote poison
prevention practices. METHODS: A probabilistic decision-analytic model simulates
healthcare costs and benefits for a hypothetical cohort of under 5 year olds. The
model compares the cost-effectiveness of home safety education, home safety
inspections, provision of free or low cost safety equipment and fitting of
equipment. Analyses are conducted from a UK National Health Service and Personal
Social Services perspective and expressed in 2012 prices. RESULTS: Education
without safety inspection, provision or fitting of equipment was the most cost
effective strategy for promoting safe storage of medicines with an incremental
cost-effectiveness ratio of L2888 (95 % credible interval (CrI) L1990-L5774) per
poison case avoided or L41,330 (95%CrI L20,007-L91,534) per QALY gained compared
with usual care. Compared to usual care, home safety interventions were not cost
effective in promoting safe storage of other household products. CONCLUSION:
Education offers better value for money than more intensive but expensive
strategies for preventing medicinal poisonings, but is only likely to be cost
effective at L30,000 per QALY gained for families in disadvantaged areas and for
those with more than one child. There was considerable uncertainty in cost
effectiveness estimates due to paucity of evidence on model parameters. Policy
makers should consider both costs and effectiveness of competing interventions to
ensure efficient use of resources.
PMID- 27488450
TI - MAD2B promotes tubular epithelial-to-mesenchymal transition and renal
tubulointerstitial fibrosis via Skp2.
AB - : The mitotic arrest deficient protein MAD2B is a well-defined anaphase-promoting
complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase zeta.
It is critical for mitotic control and DNA repair. However, the pathological role
of MAD2B in kidney diseases has not been fully elucidated. In the present study,
we aim to explore the role of MAD2B in the pathogenesis of renal
tubulointerstitial fibrosis (TIF) and the underlying mechanism. By
immunofluorescence and immunohistochemistry, we found an obvious MAD2B
enhancement in tubular area of TIF patients and unilateral ureteral obstruction
(UUO) mice. In vitro, transforming growth factor-beta1 (TGF-beta1) induced a time
dependent MAD2B accumulation prior to tubular epithelial-to-mesenchymal
transition (EMT) in a rat proximal tubular epithelial cell line, NRK-52E.
Knocking down MAD2B using siRNA dramatically inhibited TGF-beta1-induced tubular
EMT process and subsequent extracellular matrix (ECM) production. We also found
that Skp2, a confirmed APC/C-CDH1 substrate and E-cadherin destroyer, was
increased in TGF-beta1-treated proximal tubular epithelial cells, which could be
blocked by MAD2B depletion. In addition, Skp2 expression was also found to be
increased in the renal tubular area of UUO mice. Locally knocking down MAD2B
expression in the renal cortex using lentiviral transfection inhibited Skp2
expression, tubular EMT, and subsequent ECM accumulation. Taken together, our
data suggests a pro-fibrotic role of MAD2B in the pathogenesis of tubular EMT and
TIF by inducing Skp2 expression. MAD2B might be a potential target of promising
interventions for renal TIF. KEY MESSAGES: Renal fibrosis activates MAD2B
expression in renal tubules of human and mouse. TGF-beta1 contributes to MAD2B
enhancement in rat tubular epithelial cells. MAD2B depletion alleviates renal
tubulointerstitial fibrosis in vivo and in vitro. MAD2B promotes EMT transition
in rat tubular epithelial cells by inducing Skp2.
PMID- 27488451
TI - Mitochondrial aldehyde dehydrogenase 2 deficiency aggravates energy metabolism
disturbance and diastolic dysfunction in diabetic mice.
AB - : Diabetes causes energy metabolism disturbance and may lead to cardiac
dysfunction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) protects cardiac
function from myocardial damage. Therefore, understanding of its roles in
diabetic heart is critical for developing new therapeutics targeting ALDH2 and
mitochondrial function for diabetic hearts. This study investigated the impact of
ALDH2 deficiency on diastolic function and energy metabolism in diabetic mice.
Diabetes was induced in ALDH2 knockout and wild-type mice by streptozotocin.
Cardiac function was determined by echocardiography. Glucose uptake, energy
status, and metabolic profiles were used to evaluate cardiac energy metabolism.
The association between ALDH2 polymorphism and diabetes was also analyzed in
patients. Echocardiography revealed preserved systolic function and impaired
diastolic function in diabetic ALDH2-deficient mice. Energy reserves
(phosphocreatine/adenosine triphosphate ratio) were reduced in the diabetic
mutants and were associated with diastolic dysfunction. Western blot analysis
showed that diabetes induces accumulated lipid peroxidation products and
escalated AMP-activated protein kinase-LKB1 pathway. Further, ALDH2 deficiency
exacerbated the diabetes-induced deficient myocardial glucose uptake and other
perturbations of metabolic profiles. Finally, ALDH2 mutations were associated
with worse diastolic dysfunction in diabetic patients. Together, our results
demonstrate that ALDH2 deficiency and resulting energy metabolism disturbance is
a part of pathology of diastolic dysfunction of diabetic hearts, and suggest that
patients with ALDH2 mutations are vulnerable to diabetic damage. KEY MESSAGE:
ALDH2 deficiency exacerbates diastolic dysfunction in early diabetic hearts.
ALDH2 deficiency triggers decompensation of metabolic reserves and energy
metabolism disturbances in early diabetic hearts. ALDH2 deficiency potentiates
oxidative stress and AMPK phosphorylation induced by diabetes via post
translational regulation of LKB1. Diabetic patients with ALDH2 mutations are
predisposed to worse diastolic dysfunction.
PMID- 27488453
TI - Breast Hypertrophy Induced by Ombitasvir/Paritaprevir/Ritonavir and Ribavirina.
PMID- 27488454
TI - Orbital Inflammation Secondary to Zoledronic Acid, a Rare Presentation.
PMID- 27488452
TI - Resveratrol inhibits renal interstitial fibrosis in diabetic nephropathy by
regulating AMPK/NOX4/ROS pathway.
AB - : Renal interstitial fibrosis is a major pathologic feature of diabetic
nephropathy, while the pathogenesis and therapeutic interventions of diabetic
renal interstitial fibrosis are not well established. In this study, we first
demonstrated that high glucose could induce renal fibroblast (NRK-49F) cell
proliferation and activation to myofibroblasts, accompanied by a significant
increase in the intracellular levels of reactive oxygen species (ROS) derived
from nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). ROS-mediated
ERK1/2 activation was found to play a crucial role in high glucose-induced
fibroblast proliferation and activation. Resveratrol, like the NOX4-targeting
small interfering RNA (siRNA), markedly inhibited high glucose-induced fibroblast
proliferation and activation by reducing NOX4-derived ROS production. It was then
revealed that the increase in the expression of NOX4 induced by high glucose was
due to the inactivation of AMP-activated protein kinase (AMPK), which could be
reversed by resveratrol. Further in vivo investigation demonstrated that
resveratrol treatment significantly attenuated renal fibrosis in db/db mice,
accompanied by an evident increase in phospho-AMPK and decrease in NOX4. In
summary, our results suggest that high glucose can directly promote renal
fibroblasts proliferation and activation in a ROS-dependent manner, and
resveratrol is a potential therapeutic agent against diabetic renal fibrosis via
regulation of AMPK/NOX4/ROS signaling. KEY MESSAGE: Resveratrol inhibits high
glucose-induced NRK cell activation by decreasing NOX4-derived ROS. Resveratrol
inhibits high glucose-induced NOX4 expression in NRK cells via activation of
AMPK. ROS-activated ERK1/2 signaling is involved in high glucose-induced NRK cell
activation. Resveratrol attenuated renal fibrosis in db/db mice via regulation of
AMPK/NOX4/ROS signaling.
PMID- 27488455
TI - Pontibacter virosus sp. nov., isolated from a hexachlorocyclohexane-contaminated
dumpsite.
AB - A Gram-staining-negative, red-pigmented, motile, rod-shaped bacterial strain,
designated as W14T, was isolated from a hexachlorocyclohexane-contaminated
dumpsite located in the northern part of India at Ummari Village, Lucknow.
Phylogenetic analysis based on 16S rRNA gene sequence showed that the strain
belongs to the genus Pontibacter with highest sequence similarity to Pontibacter
lucknowensis DM9T (98.1 %). The 16S rRNA gene sequence similarity between strain
W14T and members of other species of the genus Pontibacter ranged from 98.1 to
94.2 %. The DNA-DNA relatedness between strain W14T and P. lucknowensis DM9T was
33.7 % and with other closely related strains was found to be less than 20 %,
confirming it to represent a novel species. The DNA G+C content of strain W14T
was 51.3 mol%. Strain W14T was oxidase- and catalase-positive. The predominant
cellular fatty acids were summed feature 4 (C17 : 1 iso I/anteiso B and C17 : 1
anteiso B/iso I), iso-C15 : 0 and iso-C17 : 0 3-OH. The polar lipid profile of
strain W14T consisted of phosphatidylethanolamine, diphosphatidylglycerol,
aminolipid and glycolipid. On the basis of the results obtained from DNA-DNA
hybridization, biochemical and physiological tests in this study, strain W14T
represents a novel species of the genus Pontibacter, for which the name
Pontibacter virosus sp. nov. is proposed. The type strain is W14T (=MCC 2932T=DSM
100231T=KCTC 42941T).
PMID- 27488456
TI - Conceptualizing and Measuring Weekend versus Weekday Alcohol Use: Item Response
Theory and Confirmatory Factor Analysis.
AB - Culturally, people tend to abstain from alcohol intake during the weekdays and
wait to consume in greater frequency and quantity during the weekends. The
current research sought to empirically justify the days representing weekday
versus weekend alcohol consumption. In study 1 (N = 419), item response theory
was applied to a two-parameter (difficulty and discrimination) model that
evaluated the days of drinking (frequency) during the typical 7-day week. Item
characteristic curves were most similar for Monday, Tuesday, and Wednesday
(prototypical weekday) and for Friday and Saturday (prototypical weekend).
Thursday and Sunday, however, exhibited item characteristics that bordered the
properties of weekday and weekend consumption. In study 2 (N = 403), confirmatory
factor analysis was applied to test six hypothesized measurement structures
representing drinks per day (quantity) during the typical week. The measurement
model producing the strongest fit indices was a correlated two-factor structure
involving separate weekday and weekend factors that permitted Thursday and Sunday
to double load on both dimensions. The proper conceptualization and accurate
measurement of the days demarcating the normative boundaries of "dry" weekdays
and "wet" weekends are imperative to inform research and prevention efforts
targeting temporal alcohol intake patterns.
PMID- 27488457
TI - KiVa Anti-Bullying Program in Italy: Evidence of Effectiveness in a Randomized
Control Trial.
AB - The present study aims to evaluate the effectiveness of the KiVa anti-bullying
program in Italy through a randomized control trial of students in grades 4 and
6. The sample involved 2042 students (51 % female; grade 4, mean age = 8.85; ds =
0.43; grade 6, mean age = 10.93; ds = 0.50); 13 comprehensive schools were
randomly assigned into intervention (KiVa) or control (usual school provision)
conditions. Different outcomes (bullying, victimization, pro-bullying attitudes,
pro-victim attitudes, empathy toward victims), analyses (longitudinal mixed model
with multiple-item scales; longitudinal prevalence of bullies and victims using
Olweus' single question), and estimates of effectiveness (Cohen's d; odds ratios)
were considered in order to compare the Italian results with those from other
countries. Multilevel models showed that KiVa reduced bullying and victimization
and increased pro-victim attitudes and empathy toward the victim in grade 4, with
effect sizes from 0.24 to 0.40. In grade 6, KiVa reduced bullying, victimization,
and pro-bullying attitudes; the effects were smaller as compared to grade 4, yet
significant (d >= 0.20). Finally, using Olweus dichotomous definition of bullies
and victims, results showed that the odds of being a victim were 1.93 times
higher for a control student than for a KiVa student in grade 4. Overall, the
findings provide evidence of the effectiveness of the program in Italy; the
discussion will focus on factors that influenced successfully the
transportability of the KiVa program in Italy.
PMID- 27488459
TI - Confirmation of association between Lewis blood group antigens and secretor
status in pemphigus vulgaris.
PMID- 27488458
TI - Epidermal growth factor receptor is expressed and active in a subset of acute
myeloid leukemia.
AB - The epidermal growth factor receptor (EGFR) inhibitor erlotinib has been shown to
induce complete remission of acute myeloid leukemia (AML) in two patients with
concurrent lung cancer and raised attention for a role of EGFR in AML whereas a
recent phase II clinical study with gefitinib in AML demonstrated a negative
result on the outcome. However, from several studies, EGFR expression in AML is
poorly defined and the role of EGFR in AML remains unclear. Herein, we report the
results of EGFR expression in AML of large cohorts of adult and pediatric AML
patients with the data of total protein and phosphorylation levels of EGFR. Our
data conclude that there is the expression of EGFR at the protein level in a
subset of AML, which was identified to be functionally active in ~15 % of AML
patients. This suggests that future studies need to be conducted with a subset of
AML patients characterized by high EGFR expression.
PMID- 27488460
TI - SM-1, a novel PAC-1 derivative, activates procaspase-3 and causes cancer cell
apoptosis.
AB - PURPOSE: To develop more potent procaspase-3 activator, 7 novel derivatives of
PAC-1 were synthesized and evaluated. Among them, SM-1 stood out for its
promising activity and good pharmacokinetics properties. The purpose of this
study is to elucidate the pharmacological mechanism of SM-1 and evaluate its
efficacy and toxicity in-depth. METHODS: To reveal the effects of SM-1 on caspase
3 activity, both in vitro activation assay and in cells fluorometric assay were
tested. The protein levels and distributions of procaspase-3 and cleaved caspase
3 were also measured by western blot and immunostaining. MTT assay, apoptosis
assay and mouse xenograft model were applied to evaluate the efficacy of SM-1.
Preliminary safety assessments also tested the acute toxicity and tissue
distribution of SM-1. RESULTS: Compared to PAC-1, SM-1 showed higher cytotoxicity
in cancer cells. Further investigation demonstrated that SM-1 relieved zinc
mediated inhibition of procaspase-3 and activated the caspase-3 activity both in
tube test and in cells. Efficacy evaluation showed SM-1-induced cell apoptosis
mainly via activation of caspase-3 and reduced tumor size in mouse xenograft
model. Its apoptosis induction efficacy was higher than PAC-1. The preliminary
safety assessment demonstrated that the overall LD50 of SM-1 lied between 500 and
1000 mg/kg and the distribution of SM-1 in brain was low. CONCLUSIONS: We
identified SM-1 as a promising antitumor candidate, which displayed enhanced
procaspase-3 activating activity and potent cytotoxicity for cancer cells but low
toxicity for normal cells.
PMID- 27488461
TI - Erratum to: Management of patients with T1b esophageal adenocarcinoma: a
retrospective cohort study on patient management and risk of metastatic disease.
PMID- 27488462
TI - Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin
inflammation while leptin stimulation induces inflammation in human
keratinocytes.
AB - Leptin is an adipocyte-derived cytokine secreted mostly by adipose tissue. Serum
leptin levels are elevated in obese individuals and correlate positively with
body mass index (BMI). Interestingly, serum leptin levels are also elevated in
patients with psoriasis and correlate positively with disease severity. Psoriasis
is associated with obesity; patients with psoriasis have a higher incidence of
obesity, and obese individuals have a higher risk of developing psoriasis.
Additionally, obese patients with psoriasis experience a more severe degree of
psoriasis. In this study, we hypothesised that leptin may link psoriasis and
obesity and plays an aggravating role in psoriasis. To investigate leptin's role
in psoriasis, we applied the widely accepted imiquimod (IMQ)-induced psoriasis
like skin inflammation mouse model on leptin-deficient (ob/ob) mice and evaluated
psoriasis severity. Moreover, we stimulated human keratinocytes with leptin and
investigated the effect on proliferation and expression of pro-inflammatory
proteins. In ob/ob mice, clinical signs of erythema, infiltration and scales in
dorsal skin and inflammation in ear skin, as measured by ear thickness, were
attenuated and compared with wt mice. Moreover, IL-17A and IL-22 mRNA expression
levels, as well as increased epidermal thickness, were significantly less
induced. In vitro, the effect of leptin stimulation on human keratinocytes
demonstrated increased proliferation and induced secretion of several pro
inflammatory proteins; two hallmarks of psoriasis. In conclusion, leptin
deficiency attenuated IMQ-induced psoriasis-like skin inflammation in a mouse
model, and leptin stimulation induced a pro-inflammatory phenotype in human
keratinocytes, thus, supporting an aggravating role of leptin in psoriasis.
PMID- 27488463
TI - Intracluster Correlation Coefficients of Household Economic and Agricultural
Outcomes in Mozambique.
AB - BACKGROUND: This article offers important statistics to evaluators planning
future evaluations in southeast Africa. There are little to no published
statistics describing the variance of southeast African agricultural and
household indicators. OBJECTIVE: We seek to publish the standard deviations,
intracluster correlation coefficients (ICCs), and R 2s from outcomes and
covariates used in a 2014 quasi-experimental evaluation of the Millennium
Challenge Corporation's Mozambique Farmer Income Support Project (FISP) and thus
guide researchers in their calculation of design effects relevant to future
evaluations in the region. METHOD: We summarize data from a roughly 168-item
farmer survey conducted in 1,227 households during June-July 2014 in coconut
farming regions of the Zambezia province in Mozambique. We report descriptive
statistics, estimates of ICC, and R 2s obtained from linear regression models
with cluster random effects. We consider three different cluster definitions.
RESULTS: We report ICCs for a range of different specifications. For the FISP
evaluation, the average design effect for education outcomes is 1.16. Average
design effects for wealth measures based on consumption are 1.23. For
agricultural-related outcomes, 1.05 is the average design effects for income
measures, 1.47 for knowledge, and 1.64 for sales of specific crops. CONCLUSION:
We offer a detailed picture of the variance structure of agricultural and other
outcomes in Mozambique. Our results indicate that the design effect associated
with these outcomes is less than the rule-of-thumb design effect (2.0) used in
nutrition studies which are commonly cited in the studies of this region.
PMID- 27488464
TI - One in 10 young people experiences a distressing sexual problem.
PMID- 27488465
TI - Wrinkled silica/titania nanoparticles with tunable interwrinkle distances for
efficient utilization of photons in dye-sensitized solar cells.
AB - Efficient light harvesting is essential for the realization of high energy
conversion efficiency in dye-sensitized solar cells (DSCs). State-of-the-art
mesoporous TiO2 photoanodes fall short for collection of long-wavelength visible
light photons, and thus there have been efforts on introduction of scattering
nanoparticles. Herein, we report the synthesis of wrinkled silica/titania
nanoparticles with tunable interwrinkle distances as scattering materials for
enhanced light harvesting in DSCs. These particles with more than 20 times larger
specific surface area (>400 m(2)/g) compared to the spherical scattering
particles (<20 m(2)/g) of the similar sizes gave rise to the dye-loading amounts,
causing significant improvements in photocurrent density and efficiency.
Moreover, dependence of spectral scattering properties of wrinkled particles on
interwrinkle distances, which was originated from difference in overall
refractive indices, was observed.
PMID- 27488466
TI - Basilar artery hypoplasia associated with changes of brainstem potential,
transcranial Doppler and perfusion-weighted imaging.
AB - OBJECTIVE: The aim of this study was to observe brainstem hemodynamic alterations
associated with basilar artery hypoplasia (BAH). METHODS: Nine hundred and fifty
two consecutive patients received emergency multimodal computed tomography;
magnetic resonance imaging and magnetic resonance angiogram during the period of
January 2011 to December 2014 were included. The vascular risk factors, brainstem
auditory evoked potential (BAEP), blink reflex (BR), transcranial Doppler (TCD)
and dynamic susceptibility contrast-enhanced perfusion-weighted imaging were
completed. RESULTS: There was significant difference in the abnormal rates of TCD
and BAEP between BAH and non-BAH patients. A positive correlation between basilar
artery diameter and systolic velocity among BAH patients was suggested. V-wave
value was used to predict posterior circulation infarction (PCI) with the
sensitivity of 0.933 and specificity of 0.50 with the cutoff value of 5.97 s.
Abnormal BR rate was also significantly different in BAH and non-BAH patients.
The latency of R2 was used to predict PCI with the sensitivity of 0.933 and
specificity of 0.50 with the cutoff value of 46.4 ms. The incidence of
hypoperfusion was higher in BAH than non-BAH group and it was significant
difference. CONCLUSION: BAH is closely associated with hemodynamic alterations
within the pons, which might contribute to vascular vertigo due to regional
hypoperfusion.
PMID- 27488467
TI - The development and initial validation of a new tool to measure self-awareness of
driving ability after brain injury.
AB - AIM: The aim of this study was to develop and provide initial validation data for
a self-awareness of on-road driving ability measure for individuals with brain
injury. METHOD: Thirty-nine individuals with Traumatic Brain Injury completed an
on-road driving assessment, the Self-Regulation Skills Interview (SRSI) and the
newly developed Brain Injury Driving Self-Awareness Measure (BIDSAM). RESULTS:
BIDSAM self, clinician and discrepancy scales demonstrated high levels of
internal consistency (alpha = 0.83-0.92). Criterion-related validity was
established by demonstrating significantly higher correlations between clinician
ratings and on-road performances, rs = 0.82, P < 0.01, compared to self-ratings,
rs = 0.45, P < 0.05. Discrepancy scores were significantly correlated with the
SRSI emergent, rs = 0.52, P < 0.01, and anticipatory awareness scores, rs =
0.37, P < 0.05, indicative of convergent validity. CONCLUSIONS: These results
provide initial support for the BIDSAM as a reliable and valid measure of self
awareness of on-road driving ability following TBI.
PMID- 27488468
TI - Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of
miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation.
AB - Atrial fibrillation (AF) is the most common sustained arrhythmia causing high
morbidity and mortality. While changing of the cellular calcium homeostasis plays
a critical role in AF, the L-type calcium channel alpha1c protein has suggested
as an important regulator of reentrant spiral dynamics and is a major component
of AF-related electrical remodeling. Our computational modeling predicted that
miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium
channel alpha1c subunit. We found that oxidized low-density lipoprotein (ox-LDL)
cholesterol significantly up-regulates both the expression of miRNA-223 and L
type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type
calcium channel protein expression, while genetic knockdown of endogenous miRNA
223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated
expression enhanced L-type calcium currents and promoted AF in mice while co
injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken
together, ox-LDL, as a known factor in AF-associated remodeling, positively
regulates miRNA-223 transcription and L-type calcium channel protein expression.
Our results implicate a new molecular mechanism for AF in which miRNA-223 can be
used as an biomarker of AF rheumatic heart disease.
PMID- 27488470
TI - Successful implementation of an Enhanced Recovery After Surgery program shortens
length of stay and improves postoperative pain, and bowel and bladder function
after colorectal surgery.
AB - BACKGROUND: Despite international data indicating that Enhanced Recovery After
Surgery (ERAS) programs, which combine evidence-based perioperative strategies,
expedite recovery after surgery, few centers have successfully adopted this
approach within the U.S. We describe the implementation and efficacy of an ERAS
program for colorectal abdominal surgery in a tertiary teaching center in the
U.S. METHODS: We used a multi-modal and continuously evolving approach to
implement an ERAS program among all patients undergoing colorectal abdominal
surgery at a single hospital at the University of California, San Francisco. 279
patients who participated in the Enhanced Recovery after Surgery program were
compared to 245 previous patients who underwent surgery prior to implementation
of the program. Primary end points were length of stay and readmission rates.
Secondary end points included postoperative pain scores, opioid consumption,
postoperative nausea and vomiting, length of urinary catheterization, and time to
first solid meal. RESULTS: ERAS decreased both median total hospital length of
stay (6.4 to 4.4 days) and post-procedure length of stay (6.0 to 4.1 days). 30
day all-cause readmission rates decreased from 21 to 9.4 %. Pain scores improved
on postoperative day 0 (3.2 to 2.1) and day 1 (3.2 to 2.6) despite decreased
opioid. Median time to first solid meal decreased from 4.7 to 2.7 days and
duration of urinary catheterization decreased from 74 to 46 h. Similar
improvements were observed in all other secondary end points. CONCLUSIONS: These
results confirm that a multidisciplinary, iterative, team-based approach is
associated with a reduction in hospital stay and an acceleration in recovery
without increasing readmission rates.
PMID- 27488469
TI - Suppression of amyloid fibrils using the GroEL apical domain.
AB - In E. coli cells, rescue of non-native proteins and promotion of native state
structure is assisted by the chaperonin GroEL. An important key to this activity
lies in the structure of the apical domain of GroEL (GroEL-AD) (residue 191-376),
which recognizes and binds non-native protein molecules through hydrophobic
interactions. In this study, we investigated the effects of GroEL-AD on the
aggregation of various client proteins (alpha-Synuclein, Abeta42, and GroES) that
lead to the formation of distinct protein fibrils in vitro. We found that GroEL
AD effectively inhibited the fibril formation of these three proteins when added
at concentrations above a critical threshold; the specific ratio differed for
each client protein, reflecting the relative affinities. The effect of GroEL-AD
in all three cases was to decrease the concentration of aggregate-forming
unfolded client protein or its early intermediates in solution, thereby
preventing aggregation and fibrillation. Binding affinity assays revealed some
differences in the binding mechanisms of GroEL-AD toward each client. Our
findings suggest a possible applicability of this minimal functioning derivative
of the chaperonins (the "minichaperones") as protein fibrillation modulators and
detectors.
PMID- 27488471
TI - Diminished IL-17A levels may protect filarial-infected individuals from
development of rheumatoid arthritis and systemic lupus erythematosus.
AB - Nematode infections have been observed to inversely correlate with autoimmune
disorders. Recently, we have shown the absence of filarial infection in patients
with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who live in
filarial-endemic areas. The mechanism(s) by which filarial-infected individuals
are protected against the development of RA or SLE are unknown. In mice CIA, an
experimental model for RA, ES-62, an execratory product of rodent filarial
nematode , has been shown to improve arthritis through suppression of the IL-17
pathway. A total of 160 individuals, 40 each of endemic normal, filarial-infected
cases, SLE and RA patients, from filarial-endemic areas, were enrolled in the
study. Plasma levels of IL17-A, IFN-alpha and TNF-alpha were quantified by enzyme
linked immunosorbent assay (ELISA). RA and SLE patients displayed significantly
higher plasma IL-17A, IFN-alpha and TNF-alpha levels compared to endemic normal
and infected individuals. Furthermore, IL-17A levels were significantly low in
participants with filarial infection compared to endemic controls ( p < 0.05).
Interestingly, plasma IL-17A levels correlated inversely with circulating
filarial antigen (CFA) ( p = 0.004, Spearman r = -0.51). Filarial infection was
associated with low plasma IL-17A levels, a mechanism by which it possibly
protects individuals in filarial-endemic areas from the development of autoimmune
disorders like RA and SLE.
PMID- 27488472
TI - Impact of concomitant medication use on belimumab efficacy and safety in patients
with systemic lupus erythematosus.
AB - Practicing physicians have requested efficacy and safety data for belimumab, when
used with specific systemic lupus erythematosus (SLE) medications. This was a
post hoc analysis of pooled efficacy and safety data from patients who received
belimumab 10 mg/kg plus standard of care (SoC) or placebo (SoC) in two Phase III,
randomized trials, BLISS-52 and BLISS-76. Patients were categorized into four
groups based on baseline concomitant medication usage: steroids only;
antimalarials (AM) only; steroids + AM; or steroids + AM + immunosuppressants
(IS). The primary endpoint was the SLE Responder Index (SRI) at Week 52. SRI over
time and individual SRI components were secondary endpoints. Time to first flare
and changes in concomitant medications were exploratory endpoints. Safety was
assessed using adverse event (AE) reporting. Across 834 patients, steroids + AM
was the largest group (n = 346, 41.5%) and AM only was the smallest (n = 77,
9.2%). Disease duration was shortest in the steroids + AM group (5.7 years vs 6.4
7.1 years); SELENA-SLEDAI scores were similar across groups. At Week 52, the
percentage of SRI responders was greatest in the steroids + AM group for
belimumab 10 mg/kg (59%) compared with placebo (44%); treatment response and SRI
component improvements were also observed across other groups. The probability of
experiencing an SLE flare was reduced in the steroids-only group for patients who
received belimumab 10 mg/kg compared with placebo (64.3% vs 78.1%; hazard ratio
0.64; 95% confidence interval: 0.42-0.96). There was little or no change in daily
AM or IS dose in any group. For all groups, there was a general decrease in
steroid dose over time; a quarter to a third of patients experienced decreased
steroid doses at Week 52. The overall safety profile was similar across treatment
arms and concomitant medication groups, with the exception of serious AEs in the
steroids + AM group (belimumab 10 mg/kg 16%, placebo 8%). The efficacy and safety
of belimumab in combination with SoC was demonstrated for various groupings of
steroids, AM and IS. These findings may improve the understanding of the safety
and efficacy of adding belimumab to different treatments.
PMID- 27488473
TI - Severe disease presentation and poor outcomes among pediatric systemic lupus
erythematosus patients in South Africa.
AB - Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem
autoimmune disease that is more severe in patients of African ancestry and
children, yet pediatric SLE on the African continent has been understudied. This
study describes a cohort of pediatric SLE (PULSE) patients in South Africa.
Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology
criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were
enrolled in this cross-sectional study from September 2013 to December 2014.
Information on clinical and serological characteristics was extracted from
medical records. Results were compared to a well-described North American
pediatric SLE cohort. Results Seventy-two South African patients were enrolled in
the study; mean age 11.5 years; 82% were girls. The racial distribution was 68%
Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with
severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus
nephritis, 63% presented with International Society of Nephrology/Renal Pathology
Society class III or IV. Patients in the PULSE cohort were more likely to be
treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort
had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease
Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE
cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8).
Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus
International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC
DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE
cohort, nine (13%) developed end-stage renal disease with six (8%) requiring
transplant, strikingly higher than North American peers (transplant rate <1%).
Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis
and significant disease damage at enrolment in the South African registry. South
African patients have severe lupus nephritis and poor renal outcomes compared to
North American peers. Our study revealed a severe disease phenotype in the PULSE
cohort resulting in poor outcomes in this high-risk population.
PMID- 27488475
TI - Fluoromicrometry: A Method for Measuring Muscle Length Dynamics with Biplanar
Videofluoroscopy.
AB - Accurate measurements of muscle length changes are essential for understanding
the biomechanics of musculoskeletal systems, and can provide insights into
muscular work, force, and power. Muscle length has typically been measured in
vivo using sonomicrometry, a method that measures distances by sending and
receiving sound pulses between piezoelectric crystals. Here, we evaluate an
alternative method, fluoromicrometry, which measures muscle length changes over
time by tracking the three-dimensional positions of implanted, radio-opaque
markers via biplanar videofluoroscopy. To determine the accuracy and precision of
fluoromicrometry, we simultaneously measured length changes of an isolated
muscle, the frog sartorius, in an in vitro setup using both fluoromicrometry and
a servomotor. For fluoromicrometry to perfectly match the results of the
servomotor, the relationship between the two measurements should be linear, with
a slope of 1. Measurements of muscle shortening from fluoromicrometry and the
motor were compared across 11 isotonic contractions. The precision of
fluoromicrometry was +/-0.09 mm, measured as the root mean square error of the
regression of fluoromicrometry versus servomotor muscle lengths. Fluoromicrometry
was also accurate: the mean slope of the fluoromicrometry-servomotor regressions
did not differ significantly from the ideal line once off-axis motion was
removed. Thus, fluoromicrometry provides a useful alternative for measuring
muscle length, especially in studies of live animals, as it permits long-term
marker implantation, wireless data collection, and increased spatial sampling.
Fluoromicrometry can also be used with X-Ray Reconstruction of Moving Morphology
to simultaneously measure muscle shortening and skeletal kinematics, providing a
potent new tool for biomechanics research.
PMID- 27488474
TI - Improving children's health and development in British Columbia through nurse
home visiting: a randomized controlled trial protocol.
AB - BACKGROUND: Nurse-Family Partnership is a nurse home visitation program that aims
to improve the lives of young mothers and their children. The program focuses on
women who are parenting for the first time and experiencing socioeconomic
disadvantage. Nurse visits start as early in pregnancy as possible and continue
until the child reaches age two years. The program has proven effective in the
United States - improving children's mental health and development and maternal
wellbeing, and showing long-term cost-effectiveness. But it is not known whether
the same benefits will be obtained in Canada, where public services differ. The
British Columbia Healthy Connections Project therefore involves a randomized
controlled trial evaluating Nurse-Family Partnership's effectiveness compared
with existing (usual) services in improving children's mental health and early
development and mother's life circumstances. The trial's main aims are to: reduce
childhood injuries by age two years (primary outcome indicator); reduce prenatal
nicotine and alcohol use; improve child cognitive and language development and
behaviour at age two years; and reduce subsequent pregnancies by 24 months
postpartum. Potential explanatory factors such as maternal mental health
(including self-efficacy) are also being assessed, as is the program's impact on
exposure to intimate-partner violence. To inform future economic evaluation, data
are also being collected on health and social service access and use.
METHODS/DESIGN: Eligible and consenting participants (N = 1040) are being
recruited prior to 28 weeks gestation then individually randomized to receive
existing services (comparison group) or Nurse-Family Partnership plus existing
services (intervention group). Nurse-Family Partnership is being delivered
following fidelity guidelines. Data are being collected during in person and
telephone interviews at: baseline; 34-36 weeks gestation; and two, 10, 18 and 24
months postpartum. Additional data will be obtained via linkages from provincial
datasets. Recruitment commenced in October 2013 and will continue for
approximately three years. DISCUSSION: This trial will provide important
information about the generalizability of Nurse-Family Partnership to the
Canadian context. Findings will be published in peer-reviewed journals and shared
with policymakers and practitioners through extensive public health
collaborations already underway. TRIAL REGISTRATION: Registered July 18, 2013
with ClinicalTrials.gov Identifier: NCT01672060 .
PMID- 27488476
TI - A needs assessment of community pharmacists for pharmacist specialization in
Canada.
AB - OBJECTIVES: Pharmacists are increasingly providing specialized services. However,
no process exists for specialist certification in Canada. The aim of this study
was to determine the extent to which Canadian community pharmacists support the
development of a certification system for specialization. METHODS: This study
utilized a cross-sectional online survey of licensed Canadian pharmacists
identified through the member databases of national and regional pharmacy
associations. A questionnaire was developed (in French and English) and
distributed via email, on behalf of the researchers, by multiple pharmacy
organizations in January 2015. Multivariate logistic regressions were conducted
to identify which sub-groups of respondents supported the creation of a
certification system and which supported mandatory certification. KEY FINDINGS: A
total of 770 responses were received. Many respondents were practising
specialists (30.0%, 205/683) and the most commonly reported specialty areas were
diabetes, smoking cessation and geriatrics. Almost 85% (n = 653/770) supported
creation of a Canadian certification process and 68.5% (n = 447/653) felt
certification should be mandatory. Respondents believed that the primary benefit
of a certification system was greater public confidence in pharmacist specialist
skills. They also felt that the most important factor in the development of the
system is to create national definitions for specialty practice. The main barrier
was the lack of reimbursement for specialty services in Canada. CONCLUSIONS: The
majority of Canadian community pharmacist respondents support the creation of a
certification process for pharmacist specialization. Future study is required to
confirm this finding in a larger sample and to determine the optimal model and
the financial feasibility of a national system in Canada.
PMID- 27488477
TI - Measuring pediatric quality of care in rural clinics-a multi-country assessment
Cambodia, Guatemala, Zambia and Kenya.
AB - OBJECTIVE: To assess the quality of care provided in rural pediatric facilities
in Cambodia, Guatemala, Kenya and Zambia DESIGN: All public health facilities in
four districts in each country were included in the assessment. Based on
utilization patterns, five children under five were selected randomly from each
facility to perform the Integrated Management of Childhood Illness (IMCI)
assessments followed by exit interviews with their caretakers. SETTING: Seventy
rural ambulatory pediatric care facilities. PARTICIPANTS: Three hundred and forty
pediatric case management observations and exit interviews with child caretakers.
MAIN OUTCOME MEASURE: IMCI index of observed quality of care for patient
assessment and counseling RESULTS: Screening for danger signs, diarrhea and fever
showed significant differences between countries (P < 0.001), with facilities in
Cambodia and Guatemala performing better. More than 90% of the children were
screened for fever in all three countries, but <75% were screened in Cambodia.
The assessment of nutritional status, checking weight against growth chart and
palmar pallor for anemia, was suboptimal in all countries. Mean consultation time
ranged from 8.2 minutes in Zambia and 12.6 minutes in Guatemala. Child age,
consultation time, health provider cadre and presenting symptoms were
significantly associated with higher quality of assessment and counseling care as
measured by the IMCI index. CONCLUSIONS: Achieving the goals of universal health
coverage in these contexts must be complimented with accelerated efforts for
capacity investments at the primary care level to ensure optimal quality of
healthcare and favorable health outcomes for children, who still experience a
high disease burden for these common IMCI conditions.
PMID- 27488478
TI - Apocynin Suppresses Lipopolysaccharide-Induced Inflammatory Responses Through the
Inhibition of MAP Kinase Signaling Pathway in RAW264.7 Cells.
AB - Apocynin, an inhibitor of NADPH oxidase, exhibits anti-inflammatory properties in
ulcerative colitis. However, the underlying mechanism by which apocynin exerts
this effect has not been clearly demonstrated. The objective of this study was to
elucidate the anti-inflammatory mechanism of apocynin in lipopolysaccharide (LPS)
challenged RAW264.7 macrophage cells. Apocynin inhibited LPS-induced
extracellular secretion of the pro-inflammatory mediators, nitric oxide (NO) and
PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2.
Apocynin also suppressed LPS-induced secretion of the pro-inflammatory cytokine,
tumor necrosis factor-alpha and LPS-induced degradation of IkappaB, which retains
NF-kappaB in the cytoplasm, consequently inhibiting the transcription of pro
inflammatory genes by NF-kappaB in the nucleus. To elucidate the underlying anti
inflammatory mechanism of apocynin, the involvement of the mitogen-activated
protein (MAP) kinases, c-jun N-terminal kinase, extracellular signal-regulated
kinases, and p38 was examined. Apocynin attenuated LPS-induced activation of all
three MAP kinases in a concentration-dependent manner. The present study
demonstrates apocynin exerts anti-inflammatory activity via the suppression of
MAP kinase signaling pathways in LPS-challenged RAW264.7 macrophage cells. Drug
Dev Res, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27488479
TI - Oncological outcomes and complication rates after laparoscopic-assisted
cryoablation: a European Registry for Renal Cryoablation (EuRECA) multi
institutional study.
AB - OBJECTIVE: To assess complication rates and intermediate oncological outcomes of
laparoscopic-assisted cryoablation (LCA) in patients with small renal masses
(SRMs). PATIENTS AND METHODS: A retrospective review of 808 patients treated with
LCA for T1a SRMs from 2005 to 2015 at eight European institutions. Complications
were analysed according to the Clavien-Dindo classification. Kaplan-Meier
analyses were used to estimate 5- and 10-year disease-free survival (DFS) and
overall survival (OS). RESULTS: The median [interquartile (IQR)] age was 67 (58
74) years. The median (IQR) tumour size was 25 (19-30) mm. The transperitoneal
approach was used in 77.7% of the patients. The median postoperative hospital
stay was 2 days. In all, 514 patients with a biopsy-confirmed renal cell
carcinoma (RCC) were available for survival analyses. The median (IQR) follow-up
for the RCC-cohort was 36 (14-56) months. A total of 32 patients (6.2%) were
diagnosed with treatment failure. The 5-/10-year DFS was 90.4%/80.0% and 5-/10
year OS was 83.2%/64.4%, respectively. A total of 134 postoperative complications
(16.6%) were reported, with severe complications (grade >=III) in 26 patients
(3.2%). An American Society of Anesthesiologists score of 3 was associated with
an increased risk of overall complications (odds ratio 2.85, 95% confidence
interval 1.32-6.20; P = 0.005). CONCLUSIONS: This large series of LCA
demonstrates satisfactory long-term oncological outcomes for SRMs. However,
although LCA is considered a minimally invasive procedure, risk of complications
should be considered when counselling patients.
PMID- 27488480
TI - Factors associated with suicide among adolescents and young adults not in mental
health treatment at time of death.
AB - BACKGROUND: Suicide is the third-leading cause of death among Illinois residents
aged 15 to 24 years. The Illinois Violent Death Reporting System (IVDRS) was
developed to help prevent these deaths by providing timely, complete data.
Understanding the circumstances surrounding suicide for those aged 15 to 24 years
who are not receiving mental health treatment can help others: (1) recognize
signs of potential crisis and (2) connect them to mental health treatment.
METHODS: The IVDRS data were collected from five Illinois counties-Cook, DuPage,
Kane, McHenry, and Peoria-from 2005 to 2010. All cases with the manner suicide,
aged 15 to 24 years, were extracted for analysis. Data were described using
frequencies and percentages, and statistical differences between groups were
determined using chi analysis. RESULTS: There were a total of 386 suicides in
those aged 15 to 24 years in IVDRS from 2005 to 2010. Most 15- to 19-year-olds
(67%) and 20- to 24-year-olds (78%) were not receiving mental health treatment at
the time of death. Among those not receiving mental health treatment, 22% and 13%
of those aged 15 to 19 and 20 to 24 years, respectively, had disclosed their
intent to commit suicide to another. One third were identified as being depressed
or in a depressed mood (not necessarily a clinical diagnosis) in both age groups.
One quarter in both age groups experienced a crisis (current, acute
precipitating, or forthcoming event) within 2 weeks of their suicides.
CONCLUSIONS: The majority of adolescents and young adults were not in mental
health treatment at the time death. Among those not in mental health treatment at
the time of death, the 15- to 19-year-olds were more likely to share their
suicidal intentions than the 20- to 24-year-olds. LEVEL OF EVIDENCE:
Epidemiological study, level IV.
PMID- 27488481
TI - The effect of gun control laws on hospital admissions for children in the United
States.
AB - BACKGROUND: Gun control laws vary greatly between states within the United
States. We hypothesized that states with strict gun laws have lower mortality and
resource utilization rates from pediatric firearms-related injury admissions.
METHODS: Kids' Inpatient Database (1997-2012) was searched for accidental (E922),
self-inflicted (E955), assault (E965), legal intervention-related (E970), or
undetermined circumstance (E985) firearm injuries. Patients were younger than 20
years and admitted for their injuries. Case incidence trends were examined for
the study period. Propensity score-matched analyses were performed using 38
covariates to compare outcomes between states with strict or lenient gun control
laws. RESULTS: Overall, 38,424 cases were identified, with an overall mortality
of 7%. Firearm injuries were most commonly assault (64%), followed by accidental
(25%), undetermined circumstance (7%), or self-inflicted (3%). A small minority
involved military-grade weapons (0.2%). Most cases occurred in lenient gun
control states (48%), followed by strict (47%) and neutral (6%).On 1:1 propensity
score-matched analysis, in-hospital mortality by case was higher in lenient
(7.5%) versus strict (6.5%) states, p = 0.013. Lenient states had a
proportionally higher rate of accidental (31%) and self-inflicted injury (4%)
versus strict states (17% and 1.6%, respectively), p < 0.001. Assault-related
injuries were proportionally lower in lenient (54%) versus strict (75%) states, p
< 0.001. Military-grade weapons were more common in lenient (0.4%) versus strict
(0.1%) states, p = 0.001. CONCLUSIONS: These findings highlight the importance of
legislative measures and their role in injury prevention, as firearm injuries are
entirely avoidable mechanisms of injury. Lenient gun control contributes not only
to worse outcomes per case, but also to a more significant and detrimental impact
on public health. LEVEL OF EVIDENCE: Epidemiologic study, level III.
PMID- 27488482
TI - An effective way to utilize daycare organizations to distribute home safety
equipment.
AB - BACKGROUND: Safety equipment installed in the home can reduce pediatric injuries.
The purpose of this study was to compare the proper use of home safety equipment
installed by an injury prevention specialist to equipment installed by a family
after distribution at a daycare. METHODS: A prospective study involving two
daycare organizations from a high-risk community was performed. Both groups
consisted of families with children 4 to 24 months old who received a packet
containing: cabinet and drawer latches, carbon monoxide (CO) detector, magnetic
phone list, and five other items. After consent was obtained, both groups
completed a prescreen survey to determine current equipment use. The self
installation group (SI) from one daycare received home safety equipment and
education for self-installation of the equipment. The professional installation
group (PI) from a comparable daycare received the same equipment and education;
however, equipment was installed for them. Assessments of equipment usage and
maintenance were performed at follow-up home visits 6 to 9 months after equipment
disbursement. Frequencies and chi analysis were used for comparisons. RESULTS:
Seventy-nine SI families and 81 PI families were enrolled. There was no
difference in home equipment use between the groups prior to interventions with
CO detectors (11.4% vs. 12.3%), cabinet locks (2.5% vs. 11.1%), drawer locks (0%
vs. 2.5%), or posted emergency numbers (24.1% vs. 19.8%). Follow-up home visits
occurred in 71 SI families (87.7%) and 75 PI families (92.6%). In both groups,
there was a significantly increased use of CO detectors (73.2% vs. 89.3%, p =
0.02), cabinet locks (38.0% vs. 78.7%, p < 0.001), and drawer locks (22.5% vs.
62.7%, p < 0.001); posted emergency number increased in both groups, but the
difference was not significant (78.9% vs. 89.3%, p = 0.11). CONCLUSION: When
provided with home safety equipment, it is used much of the time; however,
equipment installed by a professional resulted in higher use than if self
installed. For some equipment, distribution of products in daycare settings may
be just as effective as if professionally installed.
PMID- 27488483
TI - Rear-seat seatbelt laws and restraint use in rear-seated teen passengers
traveling in passenger vehicles involved in a fatal collision on a US roadway.
AB - BACKGROUND: There is widespread belief that after childhood rear-seated motor
vehicle occupants do not need to wear-seat seatbelts to travel safely. This
belief is reflected in the fact that, in many states, teen passengers can ride
legally unbelted in the rear seat of a passenger vehicle. METHODS: The Fatality
Analysis Reporting System for 2010-2011 was used to examine factors associated
with teen use of rear-seat seatbelts (n = 3,655) and with injury outcomes of
belted and unbelted rear-seated teen passengers traveling in a passenger vehicle
on a US roadway. Multilevel models controlled for nonindependence of cases using
SAS Glimmix. Odds ratio (OR) is reported with 95% confidence interval (CI).
RESULTS: Slightly more than half (50.8%) of rear-seated teens were restrained,
but this declined linearly with age from 65.8% of 13- to 14-year-olds to 43.3% of
18- to 19-year-olds. Overall, 77.0% of rear-seat mortality occurred in unbelted
teens. Passengers of belted drivers were more frequently belted (64.1% vs. 19.0%,
chi = 586.2, p < 0.0001). Nearly one-fifth (18.5%) of rear-seated teens were
ejected, with 95.8% of ejections in unrestrained teens. Presence of a rear-seat
seatbelt law was associated with higher restraint use (55.9% vs. 40.0%, chi =
89.0, p < 0.0001). However, in adjusted multilevel, multivariable models, belt
status varied by whether the seatbelt law was primary (OR, 1.60; 95% CI, 1.29
1.99) or secondary enforcement (OR, 1.33; 95% CI, 0.98-1.78). CONCLUSION:
Presence of a primary enforced rear-seat seatbelt law was associated with
significantly higher belt use. Ejection was associated with higher mortality and
being unrestrained. More than three quarters of rear-seated teens who died were
unrestrained. LEVEL OF EVIDENCE: Epidemiologic study, level III.
PMID- 27488484
TI - Severe unintentional injuries sustained by Ohio children: Is there urban/rural
variation?
AB - BACKGROUND: Determining at risk populations is essential to developing
interventions that prevent injuries. This study examined the rates of severe
unintentional injuries among urban versus rural Ohio children. METHODS:
Demographic and injury data for children 0 to 14 years old who had unintentional
injuries from January 1, 2003, to December 31, 2012, were extracted
retrospectively from the Ohio Trauma Acute Care Registry. Cases with no
designated county were excluded. Injury rates per 100,000 children 14 years or
younger were calculated annually using county of residence and US census data.
Each county was assigned an urbanization level based on population density (A =
most urban, D = most rural). RESULTS: There were 40,625 patients from 88 Ohio
counties who met the inclusion criteria; the overall annual injury rate was
231.9. The mean age was 6.7 (SD, 4.5) years; 26,035 (64.1%) were male, and 31,468
(77.5%) were white. There were 593 deaths (1.5%). Injury rates by urbanization
level were as follows: A: 120.4, B: 196.8, C: 249.1, and D: 247.4 (p = 0.04).
Nearly 50% of all deaths occurred in the most urban counties. Those in the most
urban areas were more likely to suffer injury from burns, drownings, and
suffocations and less likely to be injured by animal bites or motorized vehicle
collisions (p < 0.001). Length of stay and injury severity score were highest in
the most urban children (p < 0.001). CONCLUSION: While rural counties experienced
higher injury rates, urban areas suffered more severe injuries. Specific
mechanisms of injury differed by demographics and urbanization in Ohio,
suggesting areas for targeted injury prevention. LEVEL OF EVIDENCE: Epidemiologic
study, level III.
PMID- 27488485
TI - Rates of firearm homicide by Chicago region, age, sex, and race/ethnicity, 2005
2010.
AB - BACKGROUND: The United States reports the highest levels of firearm homicide
incidences compared to other high income countries, and the focus and causes of
these incidences within the US differ by demographic characteristics and location
such as urban versus rural environment. Despite these findings, few studies have
published on rates varied by region within a city. OBJECTIVE: This study aims to
provide descriptive analysis of the rates of firearm homicide by age, sex, and
race/ethnicity in each of the seven City of Chicago regions, and to determine if
the rates of firearm homicide differ by demographics among the seven City of
Chicago regions. METHODS: The Illinois Violent Death Reporting System conducts
routine surveillance of violent deaths. Decedents were selected according to the
following criteria: manner of death was homicide, weapon type was firearm, and
location of injury that led to death was the City of Chicago. Location of injury
was broken down by regions: North, Northwest, Center, West, South, Southwest, and
Far South. Multiyear rates per 100,000 and corresponding 95% confidence intervals
were calculated. RESULTS: There were 2,254 victims of homicide by firearm in the
City of Chicago. The overall rate across Chicago for all demographics was 12.9
(12.1-13.5 per 100,000) with an average age of 27.4. The highest age group (20
24) for firearm homicide rates was 43.2 (39.7-46.7) per 100,000. For the youngest
age group (10-14), only the Southwest (3.3-10.4) region reported any firearm
incidence. The 20 to 24 age group reported the highest rates of all age groups
within the South (107.9-151.7), West (80.3-108.2), and Far South (69.6-105.3)
regions, whereas the North and Northwest reported the lowest rates for all
regions by age. Black firearm homicide rates were 33.5 (31.9-35.1) per 100,000
versus Hispanic and non-Hispanic white firearm homicide rates of 8.5 (7.7-9.3)
and 1.2 (1-1.5) per 100,000, respectively. Lastly, the West reported the highest
firearm rates at 29.1 (657). CONCLUSION: In conclusion, Chicago is a large city
that has high variation in firearm homicide rates among its constituent regions;
therefore, an overall firearm homicide rate for the city of Chicago as a whole is
not an accurate representation of the true nature of firearm homicides. Policy
implementation may be made more effective by providing more regional analysis and
targeted interventions via multipronged initiatives to help reduce future firearm
rates, and funding for issues that address systemic poverty and adequate access
to care and medical facilities. LEVEL OF EVIDENCE: Epidemiologic study, level IV.
PMID- 27488486
TI - Evaluating distracted driving behaviors in parents of children in suburban and
rural areas of Alabama.
AB - BACKGROUND: Distracting driving is considered a dangerous epidemic in teenage
drivers and adult drivers nationwide. Cell phone use, such as talking and texting
is one of the most common driving distractions among adult and teenage drivers.
Using the model of a previously published study from New Haven, Connecticut, we
sought to investigate the driving behaviors of parents while transporting their
children in Alabama. METHODS: A comparison study was conducted of 150
participants from suburban (n = 86) and rural (n = 64) clinics in Alabama.
Participants were recruited to complete a survey regarding their cell phone usage
while driving with children. The inclusion criteria were having children younger
than 18 years, a valid driver's license, and cell phone and English speaking. The
survey consisted of 10 questions focusing on parental driving behaviors.
Following the survey, an educational intervention was provided. A Z test
proportions was used to compare the responses. RESULTS: Ninety percent of the
suburban parents reported cell phone use while driving their children as compared
with 86% of the rural parents. A significant difference was found between
suburban parents and rural parents for cell phone use in speaker mode (Z = 3.35;
p < 0.001; 95% confidence interval, 13-45), reading and sending texts while
driving (Z = 4.1; p < 0.001; 95% CI, 19-51), and surfing the Internet (Z = 4.9; p
< 0.001; 95% CI, 25-57). There was no statistical significance noted for the
following: use of Bluetooth device, talking on the cell phone when parked/at red
light, and texting while parked/at red light. CONCLUSIONS: Cell phone use among
parents while transporting children is common in the state of Alabama. Parents
living in suburban areas use cell phones in the speaker mode, read and send text
messages, and surf the Web more often when compared with parents in rural areas.
Further research on how to best implement injury prevention interventions should
be done to target high-risk areas with distracted driving behaviors. LEVEL OF
EVIDENCE: Epidemiologic study, level III.
PMID- 27488487
TI - Evaluating the reliability of an injury prevention screening tool: Test-retest
study.
AB - BACKGROUND: A standardized injury prevention (IP) screening tool can identify
family risks and allow pediatricians to address behaviors. To assess behavior
changes on later screens, the tool must be reliable for an individual and ideally
between household members. Little research has examined the reliability of safety
screening tool questions. This study utilized test-retest reliability of parent
responses on an existing IP questionnaire and also compared responses between
household parents. METHODS: Investigators recruited parents of children 0 to 1
year of age during admission to a tertiary care children's hospital. When both
parents were present, one was chosen as the "primary" respondent. Primary
respondents completed the 30-question IP screening tool after consent, and they
were re-screened approximately 4 hours later to test individual reliability. The
"second" parent, when present, only completed the tool once. All participants
received a 10-dollar gift card. Cohen's Kappa was used to estimate test-retest
reliability and inter-rater agreement. Standard test-retest criteria consider
Kappa values: 0.0 to 0.40 poor to fair, 0.41 to 0.60 moderate, 0.61 to 0.80
substantial, and 0.81 to 1.00 as almost perfect reliability. RESULTS: One hundred
five families participated, with five lost to follow-up. Thirty-two (30.5%)
parent dyads completed the tool. Primary respondents were generally mothers (88%)
and Caucasian (72%). Test-retest of the primary respondents showed their
responses to be almost perfect; average 0.82 (SD = 0.13, range 0.49-1.00).
Seventeen questions had almost perfect test-retest reliability and 11 had
substantial reliability. However, inter-rater agreement between household members
for 12 objective questions showed little agreement between responses; inter-rater
agreement averaged 0.35 (SD = 0.34, range -0.19-1.00). One question had almost
perfect inter-rater agreement and two had substantial inter-rater agreement.
CONCLUSIONS: The IP screening tool used by a single individual had excellent test
retest reliability for nearly all questions. However, when a reporter changes
from pre- to postintervention, differences may reflect poor reliability or
different subjective experiences rather than true change.
PMID- 27488488
TI - Twenty years of Injury Free Coalition for Kids: Precision focus on relentless
problems.
PMID- 27488489
TI - Teaching leadership in trauma resuscitation: Immediate feedback from a real-time,
competency-based evaluation tool shows long-term improvement in resident
performance.
AB - BACKGROUND: Limited data exist on how to develop resident leadership and
communication skills during actual trauma resuscitations. METHODS: An evaluation
tool was developed to grade senior resident performance as the team leader during
full-trauma-team activations. Thirty actions that demonstrated the Accreditation
Council for Graduate Medical Education core competencies were graded on a Likert
scale of 1 (poor) to 5 (exceptional). These actions were grouped by their
respective core competencies on 5 * 7-inch index cards. In Phase 1, baseline
performance scores were obtained. In Phase 2, trauma-focused communication in
services were conducted early in the academic year, and immediate, personalized
feedback sessions were performed after resuscitations based on the evaluation
tool. In Phase 3, residents received only evaluation-based feedback following
resuscitations. RESULTS: In Phase 1 (October 2009 to April 2010), 27 evaluations
were performed on 10 residents. In Phase 2 (April 2010 to October 2010), 28
evaluations were performed on nine residents. In Phase 3 (October 2010 to January
2012), 44 evaluations were performed on 13 residents. Total scores improved
significantly between Phases 1 and 2 (p = 0.003) and remained elevated throughout
Phase 3. When analyzing performance by competency, significant improvement
between Phases 1 and 2 (p < 0.05) was seen in all competencies (patient care,
knowledge, system-based practice, practice-based learning) with the exception of
"communication and professionalism" (p = 0.56). Statistically similar scores were
observed between Phases 2 and 3 in all competencies with the exception of
"medical knowledge," which showed ongoing significant improvement (p = 0.003).
CONCLUSIONS: Directed resident feedback sessions utilizing data from a real-time,
competency-based evaluation tool have allowed us to improve our residents'
abilities to lead trauma resuscitations over a 30-month period. Given pressures
to maximize clinical educational opportunities among work-hour constraints, such
a model may help decrease the need for costly simulation-based training. LEVEL OF
EVIDENCE: Therapeutic study, level III.
PMID- 27488490
TI - Anti-Xa-guided enoxaparin thromboprophylaxis reduces rate of deep venous
thromboembolism in high-risk trauma patients.
AB - BACKGROUND: Appropriate prophylaxis against venous thromboembolism (VTE) remains
undefined. This study evaluated an anti-Xa-guided enoxaparin thromboprophylaxis
(TPX) protocol on the incidence of VTE in high-risk trauma patients based on
Greenfield's Risk Assessment Profile (RAP) score. METHODS: This is a
retrospective observational study of patients admitted to a trauma intensive care
unit over a 12-month period. Patients were included if they received anti-Xa
guided enoxaparin TPX. Dosage was adjusted to a prophylactic peak anti-Xa level
of 0.2 to 0.4 IU/mL. Subgroup analysis was performed on high-risk patients (RAP
score >=10) who received lower-extremity duplex ultrasound surveillance for deep
vein thrombosis (DVT). Data are expressed as mean +/- SD. Significance was
assessed at p < 0.05. RESULTS: One hundred thirty-one patients received anti-Xa
guided enoxaparin TPX. Four patients were excluded for age or acute VTE on
admission. Fifty-six patients with RAP score of >=10 and surveillance duplex
evaluations were included in the subgroup analysis with mean age 43 +/- 20 years,
Injury Severity Score of 25 +/- 10, and RAP score of 16 +/- 4. Prophylactic anti
Xa levels were initially achieved in 34.6% of patients. An additional 25.2%
required 40 to 60 mg twice daily to reach prophylactic levels; 39.4% never
reached prophylactic levels. Weight, body mass index, ISS, and RAP score were
significantly higher with subprophylactic anti-Xa levels. One patient developed
bleeding complications (0.8%). No patient developed intracerebral bleeding or
heparin-induced thrombocytopenia.Nine VTE events occurred in the high-risk
subgroup, including four DVT (7.1%), all asymptomatic, and five pulmonary emboli
(8.9%). The historical rate of DVT in similar patients (ISS 31 +/- 12 and RAP
score 16 +/- 5) was 20.5%, a significant decrease (p = 0.031). Mean chest
Abbreviated Injury Scale scores were significantly higher for patients developing
pulmonary emboli than DVT, 3.0 +/- 1.1 vs. 0.0 (p < 0.001). CONCLUSIONS: Mean
chest Abbreviated Injury Scale score was higher in patients developing pulmonary
embolism. Increased weight, body mass index, ISS, and RAP score are associated
with subprophylactic anti-Xa levels. Anti-Xa-guided enoxaparin dosing reduced the
rate of DVT from 20.5% to 7.1% in high-risk trauma patients. LEVEL OF EVIDENCE:
Therapeutic study, level IV.
PMID- 27488491
TI - Effect of time to operation on mortality for hypotensive patients with gunshot
wounds to the torso: The golden 10 minutes.
AB - INTRODUCTION: Timely hemorrhage control is paramount in trauma; however, a
critical time interval from emergency department arrival to operation for
hypotensive gunshot wound (GSW) victims is not established. We hypothesize that
delaying surgery for more than 10 minutes from arrival increases all-cause
mortality in hypotensive patients with GSW. METHODS: Data of adults (n = 309)
with hypotension and GSW to the torso requiring immediate operation from January
2004 to September 2013 were retrospectively reviewed. Patients with resuscitative
thoracotomies, traumatic brain injury, transfer from outside institutions, and
operations occurring more than 1 hour after arrival were excluded. Survival
analysis using multivariate Cox regression models was used for comparison. Hazard
ratios (HRs) and 95% confidence intervals (CIs) are reported. Statistical
significance was considered at p <= 0.05. RESULTS: The study population was aged
32 +/- 12 years, 92% were male, Injury Severity Score was 24 +/- 15, systolic
blood pressure was 81 +/- 29 mm Hg, Glasgow Coma Scale score was 13 +/- 4.
Overall mortality was 27%. Mean time to operation was 19 +/- 13 minutes. After
controlling for organ injury, patients who arrived to the operating room after 10
minutes had a higher likelihood of mortality compared with those who arrived in
10 minutes or less (HR, 1.89; 95% CI, 1.10-3.26; p = 0.02); this was also true in
the severely hypotensive patients with systolic blood pressure of 70 mm Hg or
less (HR, 2.67; 95% CI, 0.97-7.34; p = 0.05). The time associated with a 50%
cumulative mortality was 16 minutes. CONCLUSIONS: Delay to the operating room of
more than 10 minutes increases the risk of mortality by almost threefold in
hypotensive patients with GSW. Protocols should be designed to shorten time in
the emergency department. Further prospective observational studies are required
to validate these findings. LEVEL OF EVIDENCE: Therapeutic study, level IV.
PMID- 27488492
TI - A novel methodology to characterize interfacility transfer strategies in a trauma
transfer network.
AB - BACKGROUND: More than half of severely injured patients are initially transported
from the scene of injury to nontrauma centers (NTCs), with many requiring
subsequent transfer to trauma center (TC) care. Definitive care in the setting of
severe injury is time sensitive. However, transferring severely injured patients
from an NTC is a complex process often fraught with delays. Selection of the
receiving TC and the mode of interfacility transport both strongly influence
total transfer time and are highly amenable to quality improvement initiatives.
METHODS: We analyzed transfer strategies, defined as the pairing of a destination
and mode of transport (land vs. rotary wing vs. fixed wing), for severely injured
adult patients. Existing transfer strategies at each NTC were derived from trauma
registry data. Geographic Information Systems network analysis was used to
identify the strategy that minimized transfer times the most as well as alternate
strategies (+15 or +30 minutes) for each NTC. Transfer network efficiency was
characterized based on optimality and stability. RESULTS: We identified 7,702
severely injured adult patients transferred from 146 NTCs to 9 TCs. Nontrauma
centers transferred severely injured patients to a median of 3 (interquartile
range, 1-4) different TCs and utilized a median of 4 (interquartile range, 2-6)
different transfer strategies. After allowing for the use of alternate transfer
strategies, 73.1% of severely injured patients were transported using
optimal/alternate strategies, and only 40.4% of NTCs transferred more than 90% of
patients using an optimal/alternate transfer strategy. Three quarters (75.5%) of
transfers occurred between NTCs and their most common receiving TC. CONCLUSION:
More than a quarter of patients with severe traumatic injuries undergoing
interfacility transport to a TC in Ontario are consistently transported using a
nonoptimal combination of destination and mode of transport. Our novel analytic
approach can be easily adapted to different system configurations and provides
actionable data that can be provided to NTCs and other stakeholders. LEVEL OF
EVIDENCE: Therapeutic study, level IV.
PMID- 27488493
TI - Activation of the protein C pathway and endothelial glycocalyx shedding is
associated with coagulopathy in an ovine model of trauma and hemorrhage.
AB - INTRODUCTION: Acute traumatic coagulopathy (ATC) is an endogenous coagulopathy
that develops following tissue injury and shock. The pathogenesis of ATC remains
poorly understood, with platelet dysfunction, activation of the protein C
pathway, and endothelial glycocalyx shedding all hypothesized to contribute to
onset. The primary aim of this study was to develop an ovine model of traumatic
coagulopathy, with a secondary aim of assessing proposed pathophysiological
mechanisms within this model. METHODS: Twelve adult Samm-Border Leicester cross
ewes were anesthetized, instrumented, and divided into three groups. The moderate
trauma group (n = 4) underwent 20% blood volume hemorrhage, bilateral tibial
fractures, and pulmonary contusions. The severe trauma group (n = 4) underwent
the same injuries, an additional hamstring crush injury, and 30% blood volume
hemorrhage. The remaining animals (n = 4) were uninjured controls. Blood samples
were collected at baseline and regularly after injury for evaluation of routine
hematology, arterial blood gases, coagulation and platelet function, and factor
V, factor VIII, plasminogen activator inhibitor 1, syndecan 1, and hyaluranon
levels. RESULTS: At 4 hours after injury, a mean increase in international
normalized ratio of 20.50% +/- 12.16% was evident in the severe trauma group and
22.50% +/- 1.00% in the moderate trauma group. An increase in activated partial
thromboplastin time was evident in both groups, with a mean of 34.25 +/- 1.71
seconds evident at 2 hours in the severe trauma animals and 34.75 +/- 2.50
seconds evident at 4 hours in the moderate trauma animals. This was accompanied
by a reduction in ROTEM EXTEM A10 in the severe trauma group to 40.75 +/- 8.42 mm
at 3 hours after injury. Arterial lactate and indices of coagulation function
were significantly correlated (R = -0.86, p < 0.0001). Coagulopathy was also
correlated with activation of the protein C pathway and endothelial glycocalyx
shedding. While a significant reduction in platelet count was evident in the
severe trauma group at 30 minutes after injury (p = 0.018), there was no evidence
of altered platelet function on induced aggregation testing. Significant
fibrinolysis was not evident. CONCLUSIONS: Animals in the severe trauma group
developed coagulation changes consistent with current definitions of ATC. The
degree of coagulopathy was correlated with the degree of shock, quantified by
arterial lactate. Activation of the protein C pathway and endothelial glycocalyx
shedding were correlated with the development of coagulopathy; however, altered
platelet function was not evident in this model.
PMID- 27488494
TI - Inter-relation between brain-derived neurotrophic factor and antioxidant enzymes
in bipolar disorder.
AB - OBJECTIVES: Accumulating evidence indicates that oxidative stress and
neurotrophins have a bidirectional relationship. In this post hoc, exploratory
analysis, we investigated the association between plasma brain-derived
neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes
glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with
bipolar disorder (BD) and healthy controls. METHODS: We measured plasma levels of
BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy
controls (n=26). Information related to current and past psychiatric/medical
history, as well as to metabolic comorbidities, was also reported. RESULTS: There
were negative correlations between BDNF, GPx (r=-.449, P<=.001) and GPx/SOD ratio
(r=-.503, P<.001), and a positive correlation between BDNF and SOD (r=.254,
P=.020). There was a moderating effect of body mass index (BMI) on the
association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034];
interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033),
and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were
significant in models that included age, gender, alcohol, tobacco and medication
use. CONCLUSIONS: There was a robust and independent correlation between
peripheral BDNF and antioxidant enzyme activities in individuals with BD, which
was moderated by metabolic comorbidities. These results reinforce the concept
that these systems are associated and further extend knowledge of the putative
effect of metabolic comorbidities in the pathophysiological substrates of BD.
PMID- 27488495
TI - Adiposity influences airway wall thickness and the asthma phenotype of HIV
associated obstructive lung disease: a cross-sectional study.
AB - BACKGROUND: Airflow obstruction, which encompasses several phenotypes, is common
among HIV-infected individuals. Obesity and adipose-related inflammation are
associated with both COPD (fixed airflow obstruction) and asthma (reversible
airflow obstruction) in HIV-uninfected persons, but the relationship to airway
inflammation and airflow obstruction in HIV-infected persons is unknown. The
objective of this study was to determine if adiposity and adipose-associated
inflammation are associated with airway obstruction phenotypes in HIV-infected
persons. METHODS: We performed a cross-sectional analysis of 121 HIV-infected
individuals assessed with pulmonary function testing, chest CT scans for measures
of airway wall thickness (wall area percent [WA%]) and adipose tissue volumes
(mediastinal and subcutaneous), as well as HIV- and adipose-related inflammatory
markers. Participants were defined as COPD phenotype (post-bronchodilator
FEV1/FVC < lower limit of normal) or asthma phenotype (doctor-diagnosed asthma or
bronchodilator response). Pearson correlation coefficients were calculated
between adipose measurements, WA%, and pulmonary function. Multivariable logistic
and linear regression models were used to determine associations of airflow
obstruction and airway remodeling (WA%) with adipose measurements and participant
characteristics. RESULTS: Twenty-three (19 %) participants were classified as the
COPD phenotype and 33 (27 %) were classified as the asthma phenotype. Body mass
index (BMI) was similar between those with and without COPD, but higher in those
with asthma compared to those without (mean [SD] 30.7 kg/m(2) [8.1] vs. 26.5
kg/m(2) [5.3], p = 0.008). WA% correlated with greater BMI (r = 0.55, p < 0.001)
and volume of adipose tissue (subcutaneous, r = 0.40; p < 0.001; mediastinal, r =
0.25; p = 0.005). Multivariable regression found the COPD phenotype associated
with greater age and pack-years smoking; the asthma phenotype with younger age,
female gender, smoking history, and lower adiponectin levels; and greater WA%
with greater BMI, younger age, higher soluble CD163, and higher CD4 counts.
CONCLUSIONS: Adiposity and adipose-related inflammation are associated with an
asthma phenotype, but not a COPD phenotype, of obstructive lung disease in HIV
infected persons. Airway wall thickness is associated with adiposity and
inflammation. Adipose-related inflammation may play a role in HIV-associated
asthma.
PMID- 27488496
TI - Pulmonary melanoma and "crazy paving" patterns in chest images: a case report and
literature review.
AB - BACKGROUND: In the lung, melanoma is mostly arranged as patterns of multiple
nodules, solitary nodules, or miliary invasions. Very rarely, it also displays a
"crazy paving" pattern (also described as a "paving stone," "flagstone," or
"slabstone" pattern), which is rarer still in discrete bilateral nodules. This
pattern is considered to be caused by pulmonary alveolar proteinosis, but its
association with various diseases is unclear. CASE PRESENTATION: A 60-year-old
man was diagnosed with pulmonary melanoma. Computed tomography revealed discrete
bilateral nodules surrounded by a "paving" pattern. A literature review found
more than 40 types of diseases that have presented with "paving" patterns in the
lung-predominantly pulmonary alveolar proteinosis, viral pneumonia, exogenous
lipoid pneumonia, bacterial pneumonia, pulmonary alveolar microlithiasis,
interstitial pneumonia, ARDS, squalene aspiration pneumonia, radiation
pneumonitis, drug-induced pneumonitis, pulmonary leptospirosis, pulmonary
hemorrhage, and pulmonary nocardiosis. CONCLUSIONS: We describe the first case of
pulmonary melanoma in the form of discrete bilateral nodules accompanied with a
computed tomography paving pattern. Although pulmonary paving patterns are rare,
more than 40 diseases reportedly display them; clinicians should consider
melanoma of the lung in differential diagnoses for patients who show such a
pattern.
PMID- 27488497
TI - Deep-water parasite diversity in Lake Tanganyika: description of two new
monogenean species from benthopelagic cichlid fishes.
AB - BACKGROUND: Lake Tanganyika is the world's second deepest lake. Its diverse
cichlid assemblage offers a unique opportunity for studying a deep-water host
parasite model in freshwater. Low host specificity and a broad host range
including representatives of the Bathybatini tribe in the only monogenean
parasite described from this habitat, Cichlidogyrus casuarinus Pariselle,
Muterezi Bukinga & Vanhove, 2015 suggest a link between lower specificity and
lower host density. Conversely, high host specificity and species richness are
reported for monogeneans of the lake's littoral cichlids. We further investigated
whether the deep-water environment in Lake Tanganyika is really monogenean
species-depauperate by investigating the monogenean fauna of Trematocara
unimaculatum (a representative of the tribe Trematocarini, the sister lineage of
the Bathybatini) and Benthochromis horii, a member of the tribe Benthochromini,
found in the same deep-water habitat as the already known hosts of C. casuarinus.
METHODS: Sclerotised structures of the collected monogenean individuals were
characterised morphologically using light microscopy and morphometrics. RESULTS:
Both examined cichlid species are infected by a single monogenean species each,
which are new to science. They are described as Cichlidogyrus brunnensis n. sp.,
infecting T. unimaculatum, and Cichlidogyrus attenboroughi n. sp., parasitising
on B. horii. Diagnostic characteristics include the distal bifurcation of the
accessory piece in C. brunnensis n. sp. and the combination of long auricles and
no heel in C. attenboroughi n. sp. In addition C. brunnensis n. sp. does not
resemble C. casuarinus, the only species of Cichlidogyrus thus far reported from
the Bathybatini. Also Cichlidogyrus attenboroughi n. sp. does not resemble any of
the monogenean species documented from the pelagic zone of the lake and is among
the few described species of Cichlidogyrus without heel. CONCLUSIONS: As two new
and non-resembling Cichlidogyrus species are described from T. unimaculatum and
B. horii, colonisation of the deep-water habitat by more than one morphotype of
Cichlidogyrus is evident. Based on morphological comparisons with previously
described monogenean species, parasite transfers with the littoral zone are
possible. Therefore, parasites of pelagic cichlids in the lake do not seem to
only mirror host phylogeny and the evolutionary history of this host-parasite
system merits further attention.
PMID- 27488498
TI - The Status of Methicillin Resistance Among Egyptian Staphylococcus aureus
Isolates: An Overview.
AB - Methicillin resistant Staphylococcus aureus (MRSA) is responsible for a large
number of antibiotic resistant infections worldwide. Understanding the
epidemiology and identifying the molecular characteristics of MRSA is elemental
in designing infection control plans to minimize the risks associated with these
infections. The prevalence of MRSA varies between the different geographic
regions. In Egypt, such knowledge is sparse, with a limited number of isolated
studies reporting the infection rate of MRSA in select parts of the country. This
work summarizes the few published reports that described MRSA prevalence and
types in Egypt.
PMID- 27488499
TI - Identification of Novel SCIRR69-Interacting Proteins During ER Stress Using SILAC
Immunoprecipitation Quantitative Proteomics Approach.
AB - Spinal cord injury and regeneration-related protein #69 (SCIRR69),also known as
cAMP-responsive element-binding protein 3-like 2, belongs to the CREB/ATF family,
some members of which play significant roles in ER stress. However, it is still
not fully elucidated whether SCIRR69 involves in ER stress and its biochemical
and functional roles during ER stress. In this study, we firstly treated fetal
rat spinal cord neuron cells (SCN) and PC12 cells with ER stress activator
thapsigargin (TG) or tunicamycin (TM) and then detected the expression pattern of
SCIRR69 in response to ER stress at mRNA and protein levels using real-time PCR
assay and immunoblotting. Results showed that the expression pattern of SCIRR69
was largely consistent with those of ER stress marker (ATF6, BIP and CHOP) at
either mRNA level or protein level, implying that SCIRR69 may play important
roles in ER stress. Subsequently, we used stable isotope labeling by amino acids
in cell culture (SILAC)-immunoprecipitation quantitative proteomics to identify
interaction partners of SCIRR69 during TG-induced ER stress in PC12 cells and
found that transitional endoplasmic reticulum ATPase (TERA) and sideroflexin-1
(SFXN1) were potential SCIRR69-interacting proteins. The interaction between
SCIRR69 and TERA or SFXN1 was validated using co-immunoprecipitation. Those
results provide some clues for novel signaling nexuses that made by interactions
between SCIRR69 and TERA or SFXN1. Our findings may facilitate a better
understanding of the fundamental functions of SCIRR69 during ER stress.
PMID- 27488500
TI - Biological evaluation of dimethylpyridine-platinum complexes with potent
antiproliferative activity.
AB - This study investigates the effect of three new platinum complexes: Pt2(2,4
dimethylpyridine)4(berenil)2 (Pt14), Pt2(3,4-dimethylpyridine)4(berenil)2 (Pt15)
and Pt2(3,5-dimethylpyridine)4(berenil)2 (Pt16) on growth and viability of breast
cancer cells and their putative mechanism(s) of cytotoxicity. Cytotoxicity was
measured with MTT assay and inhibition of [3H]thymidine incorporation into DNA in
both breast cancer cells. Results revealed that Pt14-Pt16 exhibit substantially
greater cytotoxicity than cisplatin against MCF-7 and MDA-MB-231 breast cancer
cells. In the case of human skin fibroblast cell, cytotoxicity assays
demonstrated that these compounds are less toxic to normal cells than cisplatin.
In addition, the effects of Pt14-Pt16 are investigated using the flow cytometry
assessment of annexin V binding, analysis of mitochondrial potential, markers of
apoptosis such as caspase-3, caspase-8, caspase-9, caspase-10 and defragmentation
of DNA by TUNEL assay. These results indicate that Pt14-Pt16 induce apoptosis by
the mitochondrial and external pathway.
PMID- 27488501
TI - wisepair: a computer program for individual matching in genetic tracking studies.
AB - Individual-based data sets tracking organisms over space and time are fundamental
to answering broad questions in ecology and evolution. A 'permanent' genetic tag
circumvents a need to invasively mark or tag animals, especially if there are
little phenotypic differences among individuals. However, genetic tracking of
individuals does not come without its limits; correctly matching genotypes and
error rates associated with laboratory work can make it difficult to parse out
matched individuals. In addition, defining a sampling design that effectively
matches individuals in the wild can be a challenge for researchers. Here, we
combine the two objectives of defining sampling design and reducing genotyping
error through an efficient Python-based computer-modelling program, wisepair. We
describe the methods used to develop the computer program and assess its
effectiveness through three empirical data sets, with and without reference
genotypes. Our results show that wisepair outperformed similar genotype matching
programs using previously published from reference genotype data of diurnal
poison frogs (Allobates femoralis) and without-reference (faecal) genotype sample
data sets of harbour seals (Phoca vitulina) and Eurasian otters (Lutra lutra). In
addition, due to limited sampling effort in the harbour seal data, we present
optimal sampling designs for future projects. wisepair allows for minimal
sacrifice in the available methods as it incorporates sample rerun error data,
allelic pairwise comparisons and probabilistic simulations to determine matching
thresholds. Our program is the lone tool available to researchers to define
parameters a priori for genetic tracking studies.
PMID- 27488502
TI - Controlled Synthesis of Carbon-Supported Gold Clusters for Rational Catalyst
Design.
AB - The development of novel catalysts based on metal clusters requires a rational
design principle as well as atomically precise synthetic methods. Toward this
goal, we have developed a method to precisely and independently control the size,
composition, and surface modification of heterogeneous gold clusters by
calcination of the ligand-protected Au clusters on carbon supports. We studied
the effects of these structural parameters using benzyl alcohol oxidation as a
test reaction. Unexpectedly, Au144 and Au~330 on hierarchically porous carbon
exhibited significantly higher turnover frequency than Au25 and Au38 . This size
dependence is ascribed to the difference in the geometric structures of the Au
clusters; Au144 and Au~330 have an icosahedral-based structure whereas Au25 and
Au38 have a face-centered cubic structure. Doping of a single Pd atom into Au25
supported on carbon nanotubes remarkably enhanced the catalytic activity. The
doping effect is explained in terms of the accelerated formation of the
carbocation intermediate due to electron transfer from Pd to Au, since the doped
Pd is buried within the Au clusters and is located at the interface between the
supports. Residual thiolates on Au25 affected both the activity and selectivity;
selective oxidation to benzaldehyde was achieved at optimized coverage. Non
formation of benzoic acid is due to the suppression of oxidation activity by
electron withdrawal by thiolates and non-formation of benzyl benzoate is due to
the site-isolation effect by thiolates. These results will provide useful
information for the rational design of gold-cluster-based catalysts with desired
performance.
PMID- 27488503
TI - Resilience of the Asian atmospheric circulation shown by Paleogene dust
provenance.
AB - The onset of modern central Asian atmospheric circulation is traditionally linked
to the interplay of surface uplift of the Mongolian and Tibetan-Himalayan
orogens, retreat of the Paratethys sea from central Asia and Cenozoic global
cooling. Although the role of these players has not yet been unravelled, the vast
dust deposits of central China support the presence of arid conditions and modern
atmospheric pathways for the last 25 million years (Myr). Here, we present
provenance data from older (42-33 Myr) dust deposits, at a time when the Tibetan
Plateau was less developed, the Paratethys sea still present in central Asia and
atmospheric pCO2 much higher. Our results show that dust sources and near-surface
atmospheric circulation have changed little since at least 42 Myr. Our findings
indicate that the locus of central Asian high pressures and concurrent aridity is
a resilient feature only modulated by mountain building, global cooling and sea
retreat.
PMID- 27488504
TI - Resting state brain dynamics and its transients: a combined TMS-EEG study.
AB - The brain at rest exhibits a spatio-temporally rich dynamics which adheres to
systematic behaviours that persist in task paradigms but appear altered in
disease. Despite this hypothesis, many rest state paradigms do not act directly
upon the rest state and therefore cannot confirm hypotheses about its mechanisms.
To address this challenge, we combined transcranial magnetic stimulation (TMS)
and electroencephalography (EEG) to study brain's relaxation toward rest
following a transient perturbation. Specifically, TMS targeted either the medial
prefrontal cortex (MPFC), i.e. part of the Default Mode Network (DMN) or the
superior parietal lobule (SPL), involved in the Dorsal Attention Network. TMS was
triggered by a given brain state, namely an increase in occipital alpha rhythm
power. Following the initial TMS-Evoked Potential, TMS at MPFC enhances the
induced occipital alpha rhythm, called Event Related Synchronisation, with a
longer transient lifetime than TMS at SPL, and a higher amplitude. Our findings
show a strong coupling between MPFC and the occipital alpha power. Although the
rest state is organized around a core of resting state networks, the DMN
functionally takes a special role among these resting state networks.
PMID- 27488505
TI - Variants and pitfalls on radioiodine scans in pediatric patients with
differentiated thyroid carcinoma.
AB - BACKGROUND: Potentially false-positive findings on radioiodine scans in children
with differentiated thyroid carcinoma can mimic functioning thyroid tissue and
functioning thyroid carcinomatous tissue. Such false-positive findings comprise
variants and pitfalls that can vary slightly in children as compared with adults.
OBJECTIVE: To determine the patterns and frequency of these potential false
positive findings on radioiodine scans in children with differentiated thyroid
carcinoma. MATERIALS AND METHODS: We reviewed a total of 223 radioiodine scans
from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated
thyroid carcinoma. Focal or regional activity that likely did not represent
functioning thyroid tissue or functioning thyroid carcinomatous tissue were
categorized as variants or pitfalls. The final diagnosis was confirmed by
reviewing the concurrent and follow-up clinical data, correlative
ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody
levels. We calculated the frequency of these variants and pitfalls from
diagnostic and post-therapy radioiodine scans. RESULTS: The most common variant
on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the
cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused
by prominent thyroid remnant, were the most important observed pitfalls.
CONCLUSION: Variants and pitfalls that mimic functioning thyroid tissue or
functioning thyroid carcinomatous tissue on radioiodine scan in children with
differentiated thyroid carcinoma are not infrequent, but they decrease in
frequency on successive radioiodine scans. Potential false-positive findings can
be minimized with proper knowledge of the common variants and pitfalls in
children and correlation with clinical, laboratory and imaging data.
PMID- 27488506
TI - Virtual radiology rounds: adding value in the digital era.
AB - BACKGROUND: To preserve radiology rounds in the changing health care environment,
we have introduced virtual radiology rounds, an initiative enabling clinicians to
remotely review imaging studies with the radiologist. OBJECTIVE: We describe our
initial experience with virtual radiology rounds and referring provider
impressions. MATERIALS AND METHODS: Virtual radiology rounds, a web-based
conference, use remote sharing of radiology workstations. Participants discuss
imaging studies by speakerphone. Virtual radiology rounds were piloted with the
Neonatal Intensive Care Unit (NICU) and the Congenital Cardiovascular Care Unit
(CCVCU). Providers completed a survey assessing the perceived impact and overall
value of virtual radiology rounds on patient care using a 10-point scale.
Pediatric radiologists participating in virtual radiology rounds completed a
survey assessing technical, educational and clinical aspects of this methodology.
RESULTS: Sixteen providers responded to the survey; 9 NICU and 7 CCVCU staff
(physicians, nurse practitioners and fellows). Virtual radiology rounds occurred
4-5 sessions/week with an average of 6.4 studies. Clinicians rated confidence in
their own image interpretation with a 7.4 average rating for NICU and 7.5 average
rating for CCVCU. Clinicians unanimously rated virtual radiology rounds as adding
value. NICU staff preferred virtual radiology rounds to traditional rounds and
CCVCU staff supported their new participation in virtual radiology rounds. Four
of the five pediatric radiologists participating in virtual radiology rounds
responded to the survey reporting virtual radiology rounds to be easy to
facilitate (average rating: 9.3), to moderately impact interpretation of imaging
studies (average rating: 6), and to provide substantial educational value for
radiologists (average rating: 8.3). All pediatric radiologists felt strongly that
virtual radiology rounds enable increased integration of the radiologist into the
clinical care team (average rating: 8.8). CONCLUSION: Virtual radiology rounds
are a viable alternative to radiology rounds enabling improved patient care and
education of providers.
PMID- 27488507
TI - Image quality and dose differences caused by vendor-specific image processing of
neonatal radiographs.
AB - BACKGROUND: Image processing plays an important role in optimizing image quality
and radiation dose in projection radiography. Unfortunately commercial algorithms
are black boxes that are often left at or near vendor default settings rather
than being optimized. OBJECTIVE: We hypothesize that different commercial image
processing systems, when left at or near default settings, create significant
differences in image quality. We further hypothesize that image-quality
differences can be exploited to produce images of equivalent quality but lower
radiation dose. MATERIALS AND METHODS: We used a portable radiography system to
acquire images on a neonatal chest phantom and recorded the entrance surface air
kerma (ESAK). We applied two image-processing systems (Optima XR220amx, by GE
Healthcare, Waukesha, WI; and MUSICA(2) by Agfa HealthCare, Mortsel, Belgium) to
the images. Seven observers (attending pediatric radiologists and radiology
residents) independently assessed image quality using two methods: rating and
matching. Image-quality ratings were independently assessed by each observer on a
10-point scale. Matching consisted of each observer matching GE-processed images
and Agfa-processed images with equivalent image quality. A total of 210 rating
tasks and 42 matching tasks were performed and effective dose was estimated.
RESULTS: Median Agfa-processed image-quality ratings were higher than GE
processed ratings. Non-diagnostic ratings were seen over a wider range of doses
for GE-processed images than for Agfa-processed images. During matching tasks,
observers matched image quality between GE-processed images and Agfa-processed
images acquired at a lower effective dose (11 +/- 9 MUSv; P < 0.0001).
CONCLUSION: Image-processing methods significantly impact perceived image
quality. These image-quality differences can be exploited to alter protocols and
produce images of equivalent image quality but lower doses. Those purchasing
projection radiography systems or third-party image-processing software should be
aware that image processing can significantly impact image quality when settings
are left near default values.
PMID- 27488508
TI - Evaluation of motion and its effect on brain magnetic resonance image quality in
children.
AB - BACKGROUND: Motion artifacts pose significant problems for the acquisition of MR
images in pediatric populations. OBJECTIVE: To evaluate temporal motion metrics
in MRI scanners and their effect on image quality in pediatric populations in
neuroimaging studies. MATERIALS AND METHODS: We report results from a large
pediatric brain imaging study that shows the effect of motion on MRI quality. We
measured motion metrics in 82 pediatric patients, mean age 13.4 years, in a T1
weighted brain MRI scan. As a result of technical difficulties, 5 scans were not
included in the subsequent analyses. A radiologist graded the images using a 4
point scale ranging from clinically non-diagnostic because of motion artifacts to
no motion artifacts. We used these grades to correlate motion parameters such as
maximum motion, mean displacement from a reference point, and motion-free time
with image quality. RESULTS: Our results show that both motion-free time (as a
ratio of total scan time) and average displacement from a position at a fixed
time (when the center of k-space was acquired) were highly correlated with image
quality, whereas maximum displacement was not as good a predictor. Among the 77
patients whose motion was measured successfully, 17 had average displacements of
greater than 0.5 mm, and 11 of those (14.3%) resulted in non-diagnostic images.
Similarly, 14 patients (18.2%) had less than 90% motion-free time, which also
resulted in non-diagnostic images. CONCLUSION: We report results from a large
pediatric study to show how children and young adults move in the MRI scanner and
the effect that this motion has on image quality. The results will help the
motion-correction community in better understanding motion patterns in pediatric
populations and how these patterns affect MR image quality.
PMID- 27488509
TI - Patient's age rather than severity of the arrhythmia influences the cost of
medical treatment of atrioventricular nodal or atrioventricular reciprocating
tachycardia.
AB - PURPOSE: Radiofrequency ablation (RFA) is considered the treatment of choice in
cases of atrioventricular nodal reciprocating tachycardia (AVNRT) and
atrioventricular reciprocating tachycardia (AVRT). Published studies suggest a
considerable time gap between the onset of the arrhythmia, correct diagnosis, and
RFA which may reach 10-15 years. The cost of medical treatment during that period
may be substantial. The aim of the study was to calculate the annual direct
medical cost of medical treatment of patients with AVNRT and AVRT and identify
potential factors influencing this cost. METHODS: Based on the consumption of
particular resources and the unit costs of services in 2013, we calculated the
annual direct medical cost of care for patients with AVNRT and AVRT in Poland. We
adopted the public payer's and societal perspectives. Data on health resources
was collected with a structured questionnaire and medical records of patients
scheduled for RFA. Additional analyses were performed to identify factors
influencing this cost. RESULTS: We enrolled 82 patients: mean age 43.9 +/- 14.1
years old and mean symptom duration before the RFA 13.0 +/- 11.3 years. The
median annual cost of medical treatment was 546 USD [312-957], 411 ? [278-786],
and 616 USD [369-1044], 464 ? [235-721], for the public payer and the common
perspective, respectively, with hospitalizations being the main cost component.
In multivariate analysis, only the age of the patient significantly influenced
this cost. CONCLUSIONS: The annual cost of medical treatment of AVNRT or AVRT is
substantial and dependent on the age of the patient rather than the severity of
the arrhythmia (NCT01594814).
PMID- 27488511
TI - Occupational exposures among nurses caring for chemotherapy patients
Quantitative analysis of cyclophosphamide and alpha-fluoro-beta-alanine in urine.
AB - OBJECTIVES: The aim of this study was to measure the antineoplastic drug content
in urine and verify the situation of occupational exposure of the antineoplastic
drug among nurses who care for patients undergoing chemotherapy. METHODS: Ten
female nurses who were caring for patients receiving chemotherapy were the
subjects of this study. Urine samples were collected over 24-hour periods, and
each sample was analyzed. The excretion of cyclophosphamide (CP) and alpha-fluoro
beta-alanine (FBAL) were measured in the urine of the 10 nurses. CP and FBAL were
detected separately using gas chromatography tandem mass spectrometry (GC-MSMS)
methods (Exposure Control, the Netherlands). RESULT: CP was detected in 24 urine
samples of 9 nurses. The total amount of CP excreted ranged from 5.4 to 44.2
ng/24-hours. The mean amount of CP excreted per nurse was 16.8 ng/24-hours. No
significant difference was observed between the hospital I and II. FBAL was not
detected in any of the urine samples. CP was detected in the urine of the nurses
prior to their work shift. Moreover, CP was detected in the urine of the nurses
who were not caring for patients in the intravenous drip of CP. There was most
what answered that there was hair loss in health condition. CONCLUSION: The
results reveal that almost all nurses were exposed to cyclophosphamide. Even when
the patient in the intravenous drip of CP was not being cared for, it became
clear that exposure by CP existed. As the route of the exposure to CP, the
inhalation or dermal absorption can be considered. To ensure minimum exposed to
antineoplastic drugs, suitable personal protective equipment needs to be equipped
also of various scenes of caring for chemotherapy patients. Moreover, it is
important to keep an eye on the monitoring of the antineoplastic drug in the
environment and a nurse's health condition periodically going forward.
PMID- 27488510
TI - Low-light-level therapy as a treatment for minimal hepatic encephalopathy:
behavioural and brain assessment.
AB - Minimal hepatic encephalopathy (MHE) has been shown to affect daily functioning,
quality of life, driving and overall mortality. However, little is known about
treating or diagnosing early impairments involved in MHE. We studied one of its
precipitating factors, portal hypertension. The purpose was to evaluate an
enhancement in neuronal metabolism through low-light-level therapy (LLLT) and
whether this therapy has effects on behavioural task acquisition. Rats were
trained to perform a stimulus-response task using the Morris water maze. Three
groups of animals were used: a SHAM (sham-operated) group (n = 7), a portal
hypertension (PH) group (n = 7) and a PH + LLLT group (n = 7). The triple portal
vein ligation method was used to create an animal model of the early
developmental phase of HE, and then the animals were exposed to 670 + 10 nm LED
light at a dose of 9 J/cm2 once a day for 7 days. The metabolic activity of the
brains was studied with cytochrome c oxidase histochemistry. There were
differences in behavioural performance, with an improvement in the PH + LLLT
group. Energetic brain metabolism revealed significant differences between the
groups in all the brain structures analysed, except the anterodorsal thalamus. At
the same time, in different brain networks, the PH group showed a more
complicated relationship among the structures, while the SHAM and PH + LLLT
groups had similar patterns. In this study, we provide the first preliminary
insights into the validity of LLLT as a possible intervention to improve memory
under minimal hepatic encephalopathy conditions.
PMID- 27488512
TI - Impact of drinking and smoking habits on cerebrovascular disease risk among male
employees.
AB - OBJECTIVE: We aimed to analyze the impact of drinking and smoking behavior on the
risk of developing cerebrovascular diseases among male employees aged 20-46
years. Twenty years of follow-up data of male employees enrolled in the DENSO
Health Insurance Program were used for analyses. SUBJECTS AND METHODS: Of 29,048
male employees aged 20-46 years who were enrolled in the insurance program in
1994, 25,084 (86.4%) employees underwent annual health check-ups until 2003
without missing an appointment. Of these 25,084 employees, the data of 11,784
(40.6%) employees who self-reported drinking and smoking habits were used for
analyses. The hazard ratio and 95% confidence intervals (CIs) for developing
cerebrovascular disease in 2004-2013 were calculated in four risk groups
categorized as per drinking and smoking behavior in the young group who were in
their 20s and the middle-aged group who were in their 30s-40s in 1994. Based on
their drinking behavior, participants were categorized into two groups: "not
drinking or drinking sometimes" and "drinking every day." Based on their smoking
behavior, participants were also categorized into two groups: "not smoking for 10
years" and "smoking for 10 years." RESULTS: A Cox's proportional hazard model
revealed that after controlling for body mass index, systolic blood pressure,
triglycerides, total cholesterol, fasting plasma glucose, and age, the hazard
ratios for "smoking and drinking every day" were 3.82 (95% CI: 1.40-10.41) in the
young group and 2.31 (95% CI: 1.27-4.17) in the middle-aged group. DISCUSSION:
Male employees who had been drinking and smoking for 10 years had a higher risk
of developing cerebrovascular diseases. To prevent cerebrovascular diseases among
male employees, it may be effective to offer behavior change interventions for
both drinking and smoking habits, regardless of the age group.
PMID- 27488513
TI - Anaerobic bacterial contamination after use and assessment of countermeasures a
dust mask facepiece.
PMID- 27488514
TI - Variability in concentrations of zinc in serum and feed when using zinc oxide as
a supplement for the prevention of facial eczema.
AB - AIMS: To determine the variability of concentrations of Zn in feed, when used as
a supplement to prevent facial eczema, and to determine the variability in
concentrations of Zn in serum between cows and herds that are being supplemented
with ZnO in feed, using in-shed feeders or on a feed pad. METHODS: Sixteen
commercial dairy farms in the Waikato region of New Zealand were enrolled, that
were supplementing cows with ZnO in the feed using either an automatic in-shed
feeder (ASF) or a feed pad (FP) using a feed-out or mixer wagon. On each farm 10
cows were selected by the farmer, that were assumed to be representative of the
age and liveweight of the herd. Four hours after supplement feeding, each cow was
weighed and a blood sample collected for measurement of concentrations of Zn in
serum. Three samples of feed were collected from each farm for Zn analysis, from
the beginning, middle and end of the feed being distributed. Levene's test for
homoscedasticity was used to analyse whether there were differences in variation
of individual concentrations of Zn in serum, and in the feed, between the two
feeding systems. Multivariable linear regression was used to examine associations
between age, feeding method or liveweight and concentrations of Zn in serum,
after accounting for the variability between farms. RESULTS: Of the 163 cows
sampled, concentrations of Zn in serum were between 20-35 umol/L in 75/163 (46
(95% CI=38-54)%) cows; were <20 umol/L in 71/163 (44 (95% CI=36-52)%) cows, and
>35 umol/L in 17/163 (10 (95% CI=6-16)%) cows. The variation in concentrations of
Zn in serum in individual cows differed between farms (p<0.001), and the
variability was greater for cows fed using a FP than ASF (p<0.001). There was no
difference in the variation of concentrations of Zn in feed between the two
feeding methods (p=0.54), but concentrations of Zn in serum were associated with
the amount of Zn offered in feed (p=0.008). CONCLUSIONS AND CLINICIAL RELEVENCE:
There was significant variability between farms in the concentrations of Zn in
the serum of cows being supplemented with ZnO in feed. Only 46% of cows sampled
had concentrations of Zn between 20-35 umol/L. Effective management of facial
eczema should include monitoring Zn in the feed and in serum to ensure cows are
receiving the correct dose they require.
PMID- 27488515
TI - Ultrafast Surface-Enhanced Raman Probing of the Role of Hot Electrons in Plasmon
Driven Chemistry.
AB - Hot electrons generated through plasmonic excitations in metal nanostructures
show great promise for efficiently driving chemical reactions with light.
However, the lifetime, yield, and mechanism of action of plasmon-generated hot
electrons involved in a given photocatalytic process are not well understood.
Here, we develop ultrafast surface-enhanced Raman scattering (SERS) as a direct
probe of plasmon-molecule interactions in the plasmon-catalyzed dimerization of 4
nitrobenzenethiol to p,p'-dimercaptoazobenzene. Ultrafast SERS probing of these
molecular reporters in plasmonic hot spots reveals transient Fano resonances,
which we attribute to near-field coupling of Stokes-shifted photons to hot
electron-driven metal photoluminescence. Surprisingly, we find that hot spots
that yield more photoluminescence are much more likely to drive the reaction,
which indirectly proves that plasmon-generated hot electrons induce the
photochemistry. These ultrafast SERS results provide insight into the relative
reactivity of different plasmonic hot spot environments and quantify the
ultrafast lifetime of hot electrons involved in plasmon-driven chemistry.
PMID- 27488516
TI - Factors influencing disclosure among women experiencing intimate partner violence
during pregnancy in Moshi Municipality, Tanzania.
AB - BACKGROUND: Intimate Partner Violence (IPV) has serious negative health effects
to millions of women around the globe. While disclosing IPV could open doors for
support and eventually prevent partner abuse, the factors associated with IPV
disclosure during pregnancy are not well known. The aim of this study was to
examine factors influencing IPV disclosure to any person of interest or
organization supporting women during pregnancy in Moshi Municipality, Tanzania.
METHODS: Data were from a prospective cohort study of 1123 pregnant women
followed-up by the project aiming to assess the impact of violence in the
reproductive health conducted in Moshi Municipality, Tanzania from March 2014 to
May 2015. Inclusion criteria to the current analysis were all 339 pregnant women
who reported to have experienced physical, sexual and/or emotional violence
during the index pregnancy. Data analysis used SPSS Version 20. Odds ratio with
95 % Confidence Interval (CI) for factors associated with IPV disclosure was
estimated using multivariate logistic regression models while controlling for
age, education and parity. A p-value of less than 0.05 was considered for a
statistically significant difference. RESULTS: IPV disclosure was found to be
23.3 % (n = 79). Disclosure of IPV was less likely among unemployed (OR = 0.5, 95
% CI 0.30-0.90) and women whose index pregnancy was unplanned (OR = 0.53, 95 % CI
0.29-0.98). Women who regularly participated in women's or community groups,
religious groups or political associations at least once a month had 2 times
higher odds of IPV disclosure compared to those who did not attend regularly (OR
= 2.12, 95 % CI 1.13-3.95). Most of the abused women during pregnancy who
disclosed their experience of IPV (69 %) disclosed to a member of the family of
birth followed by friends (14 %) and a member of family of the partner (11 %).
CONCLUSIONS: Most of the women who experienced IPV during pregnancy kept
suffering in silence while less than a quarter of all the abused (23.3 %)
disclosed their experience to someone. Identification of the women experiencing
IPV during pregnancy should be done as a starting point for supporting victim of
IPV. Women empowerment in economical and reproductive health will reduce their
vulnerability and facilitate disclosure of IPV for support. Key individuals who
informally support victims of IPV should be targeted in interventions.
PMID- 27488517
TI - Quality of life among working and non-working adolescents.
AB - PURPOSE: This study investigated the association between work, work intensity,
and quality of life (QOL) among adolescents in Washington State. METHODS: Data
from the 2010 Washington Healthy Youth Survey of public school students in 8, 10,
and 12th grades were analyzed. Students were categorized as working or not
working. Work intensity was classified by self-reported number of hours worked
per week. Respondent QOL was measured using the Youth Quality of Life Instrument
Healthy Youth Survey Version (YQOL-HYS). Linear regression models evaluated the
association between employment variables and scores on the YQOL-HYS. RESULTS: In
total, 27, 26, and 47 % of students in grades 8, 10, and 12 reported currently
working, respectively. For 8th and 10th graders, working was significantly
associated with lower QOL scores compared to non-working students. Across all
grades, increased work intensity was associated with significantly lower QOL.
Participation in after-school activities demonstrated a protective effect.
CONCLUSIONS: While work is often a positive experience for adolescents, among
younger teens and those who work many hours, employment during the school year
may have a deleterious impact on QOL. Further research is necessary to better
understand whether employment, particularly in early adolescence, may have
negative ramifications on QOL among young workers.
PMID- 27488518
TI - The impact of HLA-matching on reduced intensity conditioning regimen unrelated
donor allogeneic stem cell transplantation for acute myeloid leukemia in patients
above 50 years-a report from the EBMT acute leukemia working party.
AB - BACKGROUND: Data comparing fully matched and mismatched-unrelated-donor (M- and
mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following
reduced intensity conditioning regimens for acute myeloid leukemia are limited.
METHODS: We retrospectively compared the outcome of 3398 patients above the age
of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n =
108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity
conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the
cumulative incidence function, and Cox proportional hazards regression models
were used where appropriate. RESULTS: HLA matching had no impact on engraftment
(p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was
associated with higher incidence of grade II-IV acute graft-versus-host disease
(GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased
incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients
transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had
decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS)
(56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable
between all groups for patients transplanted beyond CR1. In multivariate
analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality
(HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS
(HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in
adjusted transplant outcomes between 9/10 and 8/10 mM-URD. CONCLUSIONS: Reduced
intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option
for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD
in patients not having a fully matched donor represents an alternative
therapeutic option that should be compared to other alternative donor transplant
strategies.
PMID- 27488519
TI - How randomised trials have improved the care of children with kidney disease.
AB - Randomised controlled trials (RCTs) provide the most reliable way to evaluate the
benefits and harms of interventions. Participants are divided into groups using
methods that balance the characteristics (both known and unknown) of the
participants between treatment groups; thus, differences in outcomes are due to
the interventions administered. From Cochrane Kidney and Transplant's Specialised
Register, a comprehensive registry of trials in kidney disease, we identified 482
trials involving children. The vast majority concerned urinary tract infection
(UTI; 134) and nephrotic syndrome (136). Most were small, with a median enrolment
of 46 children, with only 26 trials enrolling 200 or more participants, and of
these, 18 involved children with UTI. We discuss a number of important advances
in the care of children with UTI with or without vesico-ureteric reflux,
nephrotic syndrome, chronic kidney disease (CKD) and kidney transplantation that
have been driven largely by trials in these conditions.
PMID- 27488520
TI - Acidosis Acts through HSP90 in a PHD/VHL-Independent Manner to Promote HIF
Function and Stem Cell Maintenance in Glioma.
AB - Hypoxia is a common feature of solid tumors, which controls multiple aspects of
cancer progression. One important function of hypoxia and the hypoxia-inducible
factors (HIF) is the maintenance of cancer stem-like cells (CSC), a population of
tumor cells that possess stem cell-like properties and drives tumor growth. Among
the changes promoted by hypoxia is a metabolic shift resulting in acidification
of the tumor microenvironment. Here, we show that glioma hypoxia and acidosis
functionally cooperate in inducing HIF transcription factors and CSC maintenance.
We found that these effects did not involve the classical PHD/VHL pathway for HIF
upregulation, but instead involved the stress-induced chaperone protein HSP90.
Genetic or pharmacologic inactivation of HSP90 inhibited the increase in HIF
levels and abolished the self-renewal and tumorigenic properties of CSCs induced
by acidosis. In clinical specimens of glioma, HSP90 was upregulated in the
hypoxic niche and was correlated with a CSC phenotype. Our findings highlight the
role of tumor acidification within the hypoxic niche in the regulation of HIF and
CSC function through HSP90, with implications for therapeutic strategies to
target CSC in gliomas and other hypoxic tumors. Cancer Res; 76(19); 5845-56.
(c)2016 AACR.
PMID- 27488521
TI - Inducing Differentiation of Premalignant Hepatic Cells as a Novel Therapeutic
Strategy in Hepatocarcinoma.
AB - Hepatocellular carcinoma (HCC) represents the second leading cause of cancer
related deaths and is reported to be resistant to chemotherapy caused by tumor
initiating cells. These tumor-initiating cells express stem cell markers. An
accumulation of tumor-initiating cells can be found in 2% to 50% of all HCC and
is correlated with a poor prognosis. Mechanisms that mediate chemoresistance
include drug export, increased metabolism, and quiescence. Importantly, the
mechanisms that regulate quiescence in tumor-initiating cells have not been
analyzed in detail so far. In this research we have developed a single cell
tracking method to follow up the fate of tumor-initiating cells during
chemotherapy. Thereby, we were able to demonstrate that mCXCL1 exerts cellular
state-specific effects regulating the resistance to chemotherapeutics. mCXCL1 is
the mouse homolog of the human IL8, a chemokine that correlates with poor
prognosis in HCC patients. We found that mCXCL1 blocks differentiation of
premalignant cells and activates quiescence in tumor-initiating cells. This
process depends on the activation of the mTORC1 kinase. Blocking of the mTORC1
kinase induces differentiation of tumor-initiating cells and allows their
subsequent depletion using the chemotherapeutic drug doxorubicin. Our work
deciphers the mCXCL1-mTORC1 pathway as crucial in liver cancer stem cell
maintenance and highlights it as a novel target in combination with conventional
chemotherapy. Cancer Res; 76(18); 5550-61. (c)2016 AACR.
PMID- 27488522
TI - Structural Basis for Induction of Peripheral Neuropathy by Microtubule-Targeting
Cancer Drugs.
AB - Peripheral neuropathy is a serious, dose-limiting side effect of cancer treatment
with microtubule-targeting drugs. Symptoms present in a "stocking-glove"
distribution, with longest nerves affected most acutely, suggesting a length
dependent component to the toxicity. Axonal transport of ATP-producing
mitochondria along neuronal microtubules from cell body to synapse is crucial to
neuronal function. We compared the effects of the drugs paclitaxel and
ixabepilone that bind along the lengths of microtubules and the drugs eribulin
and vincristine that bind at microtubule ends, on mitochondrial trafficking in
cultured human neuronal SK-N-SH cells and on axonal transport in mouse sciatic
nerves. Antiproliferative concentrations of paclitaxel and ixabepilone
significantly inhibited the anterograde transport velocity of mitochondria in
neuronal cells, whereas eribulin and vincristine inhibited transport only at
significantly higher concentrations. Confirming these observations, anterogradely
transported amyloid precursor protein accumulated in ligated sciatic nerves of
control and eribulin-treated mice, but not in paclitaxel-treated mice, indicating
that paclitaxel inhibited anterograde axonal transport, whereas eribulin did not.
Electron microscopy of sciatic nerves of paclitaxel-treated mice showed reduced
organelle accumulation proximal to the ligation consistent with inhibition of
anterograde (kinesin based) transport by paclitaxel. In contrast, none of the
drugs significantly affected retrograde (dynein based) transport in neuronal
cells or mouse nerves. Collectively, these results suggest that paclitaxel and
ixabepilone, which bind along the lengths and stabilize microtubules, inhibit
kinesin-based axonal transport, but not dynein-based transport, whereas the
microtubule-destabilizing drugs, eribulin and vincristine, which bind
preferentially to microtubule ends, have significantly less effect on all
microtubule-based axonal transport. Cancer Res; 76(17); 5115-23. (c)2016 AACR.
PMID- 27488523
TI - Exercise and Prognosis on the Basis of Clinicopathologic and Molecular Features
in Early-Stage Breast Cancer: The LACE and Pathways Studies.
AB - To investigate whether the impact of postdiagnosis exercise on breast cancer
outcomes in women diagnosed with early-stage breast cancer differs on the basis
of tumor clinicopathologic and molecular features. Using a prospective design,
6,211 patients with early-stage breast cancer from two large population-based
cohort studies were studied. Age-adjusted and multivariable Cox regression models
were performed to determine the relationship between exercise exposure (total MET
hours/week) and recurrence and breast cancer-related death for: (i) all patients
("unselected" cohort), and on the basis of (ii) classic clinicopathologic
features, (iii) clinical subtypes, (iv) PAM50-based molecular intrinsic subtypes,
and (v) individual PAM50 target genes. After a median follow-up of 7.2 years, in
the unselected cohort (n = 6,211) increasing exercise exposure was not associated
with a reduction in the risk of recurrence (adjusted Ptrend = 0.60) or breast
cancer-related death (adjusted Ptrend = 0.39). On the basis of clinicopathologic
features, an exercise-associated reduction in breast cancer-related death was
apparent for tumors <2 cm [HR, 0.50; 95% confidence interval (CI), 0.34-0.72],
well/moderately differentiated tumors (HR, 0.63; 95% CI, 0.43-0.91), and ER
positive tumors (HR, 0.72; 95% CI, 0.53-0.97). Stratification by clinical subtype
indicated that the ER(+)/PR(+)/HER2(-)/low-grade clinical subtype was
preferentially responsive to exercise (recurrence: adjusted HR, 0.63; 95% CI,
0.45-0.88; breast cancer-related death: adjusted HR, 0.57; 95% CI, 0.37-0.86).
The impact of exercise on cancer outcomes appears to differ as a function of
pathologic and molecular features in early-stage breast cancer. Cancer Res;
76(18); 5415-22. (c)2016 AACR.
PMID- 27488524
TI - In Vivo FRET Imaging of Tumor Endothelial Cells Highlights a Role of Low PKA
Activity in Vascular Hyperpermeability.
AB - Vascular hyperpermeability is a pathological hallmark of cancer. Previous in
vitro studies have elucidated roles of various signaling molecules in vascular
hyperpermeability; however, the activities of such signaling molecules have not
been examined in live tumor tissues for technical reasons. Here, by in vivo two
photon excitation microscopy with transgenic mice expressing biosensors based on
Forster resonance energy transfer, we examined the activity of protein kinase A
(PKA), which maintains endothelial barrier function. The level of PKA activity
was significantly lower in the intratumoral endothelial cells than the
subcutaneous endothelial cells. PKA activation with a cAMP analogue alleviated
the tumor vascular hyperpermeability, suggesting that the low PKA activity in the
endothelial cells may be responsible for the tumor-tissue hyperpermeability.
Because the vascular endothelial growth factor (VEGF) receptor is a canonical
inducer of vascular hyperpermeability and a molecular target of anticancer drugs,
we examined the causality between VEGF receptor activity and the PKA activity.
Motesanib, a kinase inhibitor for VEGF receptor, activated tumor endothelial PKA
and reduced the vascular permeability in the tumor. Conversely, subcutaneous
injection of VEGF decreased endothelial PKA activity and induced
hyperpermeability of subcutaneous blood vessels. Notably, in cultured human
umbilical vascular endothelial cells, VEGF activated PKA rather than decreasing
its activity, highlighting the remarkable difference between its actions in vitro
and in vivo These data suggested that the VEGF receptor signaling pathway
increases vascular permeability, at least in part, by reducing endothelial PKA
activity in the live tumor tissue. Cancer Res; 76(18); 5266-76. (c)2016 AACR.
PMID- 27488525
TI - Multivalent Peptoid Conjugates Which Overcome Enzalutamide Resistance in Prostate
Cancer Cells.
AB - Development of resistance to antiandrogens for treating advanced prostate cancer
is a growing concern and extends to recently developed therapeutics, including
enzalutamide. Therefore, new strategies to block androgen receptor (AR) function
in prostate cancer are required. Here, we report the characterization of a
multivalent conjugate presenting two bioactive ethisterone ligands arrayed as
spatially defined pendant groups on a peptoid oligomer. The conjugate, named
Multivalent Peptoid Conjugate 6 (MPC6), suppressed the proliferation of multiple
AR-expressing prostate cancer cell lines including those that failed to respond
to enzalutamide and ARN509. The structure-activity relationships of MPC6 variants
were evaluated, revealing that increased spacing between ethisterone moieties and
changes in peptoid topology eliminated its antiproliferative effect, suggesting
that both ethisterone ligand presentation and scaffold characteristics contribute
to MPC6 activity. Mechanistically, MPC6 blocked AR coactivator-peptide
interaction and prevented AR intermolecular interactions. Protease sensitivity
assays suggested that the MPC6-bound AR induced a receptor conformation distinct
from that of dihydrotestosterone- or enzalutamide-bound AR. Pharmacologic studies
revealed that MPC6 was metabolically stable and displayed a low plasma clearance
rate. Notably, MPC6 treatment reduced tumor growth and decreased Ki67 and AR
expression in mouse xenograft models of enzalutamide-resistant LNCaP-abl cells.
Thus, MPC6 represents a new class of compounds with the potential to combat
treatment-resistant prostate cancer. Cancer Res; 76(17); 5124-32. (c)2016 AACR.
PMID- 27488526
TI - Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets
in Urothelial Carcinoma.
AB - Greater knowledge concerning tumor heterogeneity and clonality is needed to
determine the impact of targeted treatment in the setting of bladder cancer. In
this study, we performed whole-exome, transcriptome, and deep-focused sequencing
of metachronous tumors from 29 patients initially diagnosed with early-stage
bladder tumors (14 with nonprogressive disease and 15 with progressive disease).
Tumors from patients with progressive disease showed a higher variance of the
intrapatient mutational spectrum and a higher frequency of APOBEC-related
mutations. Allele-specific expression was also higher in these patients,
particularly in tumor suppressor genes. Phylogenetic analysis revealed a common
origin of the metachronous tumors, with a higher proportion of clonal mutations
in the ancestral branch; however, 19 potential therapeutic targets were
identified as both ancestral and tumor-specific alterations. Few subclones were
present based on PyClone analysis. Our results illuminate tumor evolution and
identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19);
5894-906. (c)2016 AACR.
PMID- 27488527
TI - Monocyte Induction of E-Selectin-Mediated Endothelial Activation Releases VE
Cadherin Junctions to Promote Tumor Cell Extravasation in the Metastasis Cascade.
AB - Tumor cells interact with blood constituents and these interactions promote
metastasis. Selectins are vascular receptors facilitating interactions of tumor
cells with platelets, leukocytes, and endothelium, but the role of endothelial E
selectin remains unclear. Here we show that E-selectin is a major receptor for
monocyte recruitment to tumor cell-activated endothelium. Experimental and
spontaneous lung metastasis using murine tumor cells, without E-selectin ligands,
were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted
endothelial activation, resulting in enhanced endothelial E-selectin expression.
The recruitment of inflammatory monocytes to metastasizing tumor cells was
dependent on the local endothelial activation and the presence of E-selectin.
Monocytes promoted transendothelial migration of tumor cells through the
induction of E-selectin-dependent endothelial retractions and a subsequent
modulation of tight junctions through dephosphorylation of VE-cadherin. Thus,
endothelial E-selectin shapes the tumor microenvironment through the recruitment,
adhesion, and activation of monocytes that facilitate tumor cell extravasation
and thereby metastasis. These findings provide evidence that endothelial E
selectin is a novel factor contributing to endothelial retraction required for
efficient lung metastasis. Cancer Res; 76(18); 5302-12. (c)2016 AACR.
PMID- 27488528
TI - Splenic Marginal Zone Granulocytes Acquire an Accentuated Neutrophil B-Cell
Helper Phenotype in Chronic Lymphocytic Leukemia.
AB - Recruitment of tumor-associated macrophages and neutrophils (TAM and TAN) to
solid tumors contributes to immunosuppression in the tumor microenvironment;
however, their contributions to lymphoid neoplasms are less clear. In human
chronic lymphocytic leukemia (CLL), tumor B cells lodge in lymph nodes where
interactions with the microenvironment occur. Tumor cell homing stimulates
proliferation, such that engagement of the B-cell receptor is important for
malignant progression. In the EMU-Tcl1 murine model of CLL, we identified gene
expression signatures indicative of a skewed polarization in the phenotype of
monocytes and neutrophils. Selective ablation of either of these cell populations
in mice delayed leukemia growth. Despite tumor infiltration of these immune
cells, a systemic inflammation was not detected. Notably, in progressive CLL,
splenic neutrophils were observed to differentiate toward a B-cell helper
phenotype, a process promoted by the induction of leukemia-associated IL10 and
TGFbeta. Our results suggest that targeting aberrant neutrophil differentiation
and restoring myeloid cell homeostasis could limit the formation of survival
niches for CLL cells. Cancer Res; 76(18); 5253-65. (c)2016 AACR.
PMID- 27488529
TI - TG2 and NF-kappaB Signaling Coordinates the Survival of Mantle Cell Lymphoma
Cells via IL6-Mediated Autophagy.
AB - Expression of the transglutaminase TG2 has been linked to constitutive activation
of NF-kappaB and chemotherapy resistance in mantle cell lymphoma (MCL) cells. TG2
forms complexes with NF-kappaB components, but mechanistic insights that could be
used to leverage therapeutic responses has been lacking. In the current study, we
address this issue with the discovery of an unexpected role for TG2 in triggering
autophagy in drug-resistant MCL cells through induction of IL6. CRISPR-mediated
silencing of TG2 delayed apoptosis while overexpressing TG2 enhanced tumor
progression. Under stress, TG2 and IL6 mediate enhanced autophagy formation to
promote MCL cell survival. Interestingly, the autophagy product ATG5 involved in
autophagosome elongation positively regulated TG2/NF-kappaB/IL6 signaling,
suggesting a positive feedback loop. Our results uncover an interconnected
network of TG2/NF-kappaB and IL6/STAT3 signaling with autophagy regulation in MCL
cells, the disruption of which may offer a promising therapeutic strategy. Cancer
Res; 76(21); 6410-23. (c)2016 AACR.
PMID- 27488531
TI - An In Vivo Reporter to Quantitatively and Temporally Analyze the Effects of
CDK4/6 Inhibitor-Based Therapies in Melanoma.
AB - Aberrant cell-cycle progression is a hallmark feature of cancer cells. Cyclin
dependent kinases 4 and 6 (CDK4/6) drive progression through the G1 stage of the
cell cycle, at least in part, by inactivating the tumor suppressor,
retinoblastoma. CDK4/6 are targetable and the selective CDK4/6 inhibitor,
palbociclib, was recently FDA approved for the treatment of estrogen receptor
positive, HER2-negative advanced breast cancer. In cutaneous melanoma, driver
mutations in NRAS and BRAF promote CDK4/6 activation, suggesting that inhibitors
such as palbociclib are likely to provide therapeutic benefit in combination with
BRAF inhibitors and/or MEK inhibitors that are FDA-approved. However, the
determinants of the response to CDK4/6 inhibitors alone and in combination with
other targeted inhibitors are poorly defined. Furthermore, in vivo systems to
quantitatively and temporally measure the efficacy of CDK4/6 inhibitors and
determine the extent that CDK activity is reactivated during acquired resistance
are lacking. Here, we describe the heterogeneous effects of CDK4/6 inhibitors,
the expression of antiapoptotic proteins that associate with response to CDK4/6
and MEK inhibitors, and the development of a luciferase-based reporter system to
determine the effects of CDK4/6 inhibitors alone and in combination with MEK
inhibitors in melanoma xenografts. These findings are likely to inform on-going
and future clinical trials utilizing CDK4/6 inhibitors in cutaneous melanoma.
Cancer Res; 76(18); 5455-66. (c)2016 AACR.
PMID- 27488530
TI - JARID1B Enables Transit between Distinct States of the Stem-like Cell Population
in Oral Cancers.
AB - The degree of heterogeneity among cancer stem cells (CSC) remains ill-defined and
may hinder effective anti-CSC therapy. Evaluation of oral cancers for such
heterogeneity identified two compartments within the CSC pool. One compartment
was detected using a reporter for expression of the H3K4me3 demethylase JARID1B
to isolate a JARID1B(high) fraction of cells with stem cell-like function.
JARID1B(high) cells expressed oral CSC markers including CD44 and ALDH1 and
showed increased PI3K pathway activation. They were distinguished from a fraction
in a G0-like cell-cycle state characterized by low reactive oxygen species and
suppressed PI3K/AKT signaling. G0-like cells lacked conventional CSC markers but
were primed to acquire stem cell-like function by upregulating JARID1B, which
directly mediated transition to a state expressing known oral CSC markers. The
transition was regulated by PI3K signals acting upstream of JARID1B expression,
resulting in PI3K inhibition depleting JARID1B(high) cells but expanding the G0
like subset. These findings define a novel developmental relationship between two
cell phenotypes that may jointly contribute to CSC maintenance. Expansion of the
G0-like subset during targeted depletion of JARID1B(high) cells implicates it as
a candidate therapeutic target within the oral CSC pool. Cancer Res; 76(18); 5538
49. (c)2016 AACR.
PMID- 27488532
TI - The Genomic Landscape of Pancreatic and Periampullary Adenocarcinoma.
AB - Despite advances in diagnostics, less than 5% of patients with periampullary
tumors experience an overall survival of five years or more. Periampullary tumors
are neoplasms that arise in the vicinity of the ampulla of Vater, an enlargement
of liver and pancreas ducts where they join and enter the small intestine. In
this study, we analyzed copy number aberrations using Affymetrix SNP 6.0 arrays
in 60 periampullary adenocarcinomas from Oslo University Hospital to identify
genome-wide copy number aberrations, putative driver genes, deregulated pathways,
and potential prognostic markers. Results were validated in a separate cohort
derived from The Cancer Genome Atlas Consortium (n = 127). In contrast to many
other solid tumors, periampullary adenocarcinomas exhibited more frequent genomic
deletions than gains. Genes in the frequently codeleted region 17p13 and 18q21/22
were associated with cell cycle, apoptosis, and p53 and Wnt signaling. By
integrating genomics and transcriptomics data from the same patients, we
identified CCNE1 and ERBB2 as candidate driver genes. Morphologic subtypes of
periampullary adenocarcinomas (i.e., pancreatobiliary or intestinal) harbor many
common genomic aberrations. However, gain of 13q and 3q, and deletions of 5q were
found specific to the intestinal subtype. Our study also implicated the use of
the PAM50 classifier in identifying a subgroup of patients with a high
proliferation rate, which had impaired survival. Furthermore, gain of 18p11
(18p11.21-23, 18p11.31-32) and 19q13 (19q13.2, 19q13.31-32) and subsequent
overexpression of the genes in these loci were associated with impaired survival.
Our work identifies potential prognostic markers for periampullary tumors, the
genetic characterization of which has lagged. Cancer Res; 76(17); 5092-102.
(c)2016 AACR.
PMID- 27488533
TI - Stimulation of Natural Killer Cell-Mediated Tumor Immunity by an IL15/TGFbeta
Neutralizing Fusion Protein.
AB - The clinical efficacy of immune cytokines used for cancer therapy is hampered by
elements of the immunosuppressive tumor microenvironment such as TGFbeta. Here we
demonstrate that FIST15, a recombinant chimeric protein composed of the T-cell
stimulatory cytokine IL15, the sushi domain of IL15Ralpha and a TGFbeta ligand
trap, can overcome immunosuppressive TGFbeta to effectively stimulate the
proliferation and activation of natural killer (NK) and CD8+ T cells with potent
antitumor properties. FIST15-treated NK and CD8+ T cells produced more IFNgamma
and TNFalpha compared with treatment with IL15 and a commercially available
TGFbeta receptor-Fc fusion protein (sTbetaRII) in the presence of TGFbeta. Murine
B16 melanoma cells, which overproduce TGFbeta, were lysed by FIST15-treated NK
cells in vitro at doses approximately 10-fold lower than NK cells treated with
IL15 and sTbetaRII. Melanoma cells transduced to express FIST15 failed to
establish tumors in vivo in immunocompetent murine hosts and could only form
tumors in beige mice lacking NK cells. Mice injected with the same cells were
also protected from subsequent challenge by unmodified B16 melanoma cells.
Finally, mice with pre-established B16 melanoma tumors responded to FIST15
treatment more strongly compared with tumors treated with control cytokines.
Taken together, our results offer a preclinical proof of concept for the use of
FIST15 as a new class of biological therapeutics that can coordinately neutralize
the effects of immunosuppressive TGFbeta in the tumor microenvironment while
empowering tumor immunity. Cancer Res; 76(19); 5683-95. (c)2016 AACR.
PMID- 27488536
TI - Exceptional Single-Molecule Transport Properties of Ladder-Type Heteroacene
Molecular Wires.
AB - A series of ladder-type fused heteroacenes consisting of thiophenes and
benzothiophenes were synthesized and functionalized with thiol groups for single
molecule electrical measurements via a scanning tunneling microscopy break
junction method. It was found that this molecular wire system possesses
exceptional charge transport properties with weak length dependence. The
tunneling decay constant beta was estimated to be 0.088 and 0.047 A(-1) under 0.1
and 0.5 bias, respectively, which is one of the lowest beta values among other
non-metal-containing molecular wires, indicating that a planar ladder structure
favors charge transport. Transition voltage spectroscopy showed that the energy
barrier decreases as the length of the molecule increases. The general trend of
the energy offsets derived from the transition voltage via the Newns-Anderson
model agrees well with that of the Fermi/HOMO energy level difference.
Nonequilibrium Green's function/density functional theory was used to further
investigate the transport process in these molecular wires.
PMID- 27488534
TI - Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer
Risk.
AB - Metabolism of nicotine by cytochrome P450 2A6 (CYP2A6) is a suspected determinant
of smoking dose and, consequently, lung cancer risk. We conducted a genome-wide
association study (GWAS) of CYP2A6 activity, as measured by the urinary ratio of
trans-3'-hydroxycotinine and its glucuronide conjugate over cotinine (total
3HCOT/COT), among 2,239 smokers in the Multiethnic Cohort (MEC) study. We
identified 248 CYP2A6 variants associated with CYP2A6 activity (P < 5 * 10-8).
CYP2A6 activity was correlated (r = 0.32; P < 0.0001) with total nicotine
equivalents (a measure of nicotine uptake). When we examined the effect of these
variants on lung cancer risk in the Transdisciplinary Research in Cancer of the
Lung (TRICL) consortium GWAS dataset (13,479 cases and 43,218 controls), we found
that the vast majority of these individual effects were directionally consistent
and associated with an increased lung cancer risk. Two hundred and twenty-six of
the 248 variants associated with CYP2A6 activity in the MEC were available in
TRICL. Of them, 81% had directionally consistent risk estimates, and six were
globally significantly associated with lung cancer. When conditioning on nine
known functional variants and two deletions, the top two SNPs (rs56113850 in MEC
and rs35755165 in TRICL) remained significantly associated with CYP2A6 activity
in MEC and lung cancer in TRICL. The present data support the hypothesis that a
greater CYP2A6 activity causes smokers to smoke more extensively and be exposed
to higher levels of carcinogens, resulting in an increased risk for lung cancer.
Although the variants identified in these studies may be used as risk prediction
markers, the exact causal variants remain to be identified. Cancer Res; 76(19);
5768-76. (c)2016 AACR.
PMID- 27488537
TI - Diffusion-Induced Hydrophilic Conversion of Polydimethylsiloxane/Block-Type
Phospholipid Polymer Hybrid Substrate for Temporal Cell-Adhesive Surface.
AB - In this study, diffusion-induced hydrophobic-hydrophilic conversion of the
surface of the cross-linked polydimethylsiloxane (PDMS) substrate was realized by
employing a simple swelling-deswelling process of PDMS substrate in a block-type
polymer solution with the aim of development of a temporal cell-adhesive
substrate. The ABA block-type polymer composed of poly(2-methacryloyloxyethyl
phosphorylcholine) (PMPC) segment and PDMS segment with over 70% of
dimethylsiloxane unit composition could be successfully incorporated in the PDMS
substrate during the swelling-deswelling process to prepare the PDMS/phospholipid
block copolymer hybrid substrates. During the aging process of the PDMS substrate
for 4 days in aqueous medium, its surface property changed gradually from
hydrophobic to hydrophilic. X-ray photoelectron spectroscopy and atomic force
microscopy data provided strong evidence that the time-dependent hydrophilic
conversion of the PDMS/block-type phospholipid polymer hybrid substrate was
induced by the diffusion of the hydrophilic PMPC segment in the block-type
polymer to be tethered on the substrate. During the hydrophilic conversion
process, surface-adsorbed fibronectin was gradually desorbed from the substrate
surface, and this resulted in successful detachment of two-dimensional connected
cell crowds.
PMID- 27488535
TI - Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in
Rhabdomyosarcoma.
AB - Rhabdomyosarcoma (RMS) is an aggressive soft tissue cancer characterized by
disturbed myogenic differentiation. Here we report a role for the oxidative
stress response factor HO-1 in progression of RMS. We found that HO-1 was
elevated and its effector target miR-206 decreased in RMS cell lines and clinical
primary tumors of the more aggressive alveolar phenotype (aRMS). In embryonal RMS
(eRMS), HO-1 expression was induced by Pax3/7-FoxO1, an aRMS hallmark oncogene,
followed by a drop in miR-206 levels. Inhibition of HO-1 by tin protoporphyrin
(SnPP) or siRNA downregulated Pax3/7-FoxO1 target genes and induced a myogenic
program in RMS. These effects were not mediated by altered myoD expression;
instead, cells with elevated HO-1 produced less reactive oxygen species,
resulting in nuclear localization of HDAC4 and miR-206 repression. HO-1
inhibition by SnPP reduced growth and vascularization of RMS tumors in vivo
accompanied by induction of miR-206. Effects of SnPP on miR-206 expression and
RMS tumor growth were mimicked by pharmacologic inhibition of HDAC. Thus, HO-1
inhibition activates an miR-206-dependent myogenic program in RMS, offering a
novel therapeutic strategy for treatment of this malignancy. Cancer Res; 76(19);
5707-18. (c)2016 AACR.
PMID- 27488538
TI - Sensory neuropathy in progressive motor neuronopathy (pmn) mice is associated
with defects in microtubule polymerization and axonal transport.
AB - Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) are now
recognized as multi-system disorders also involving various non-motor neuronal
cell types. The precise extent and mechanistic basis of non-motor neuron damage
in human ALS and ALS animal models remain however unclear. To address this, we
here studied progressive motor neuronopathy (pmn) mice carrying a missense loss
of-function mutation in tubulin binding cofactor E (TBCE). These mice manifest a
particularly aggressive form of motor axon dying back and display a microtubule
loss, similar to that induced by human ALS-linked TUBA4A mutations. Using whole
nerve confocal imaging of pmn * thy1.2-YFP16 fluorescent reporter mice and
electron microscopy, we demonstrate axonal discontinuities, bead-like spheroids
and ovoids in pmn suralis nerves indicating prominent sensory neuropathy. The
axonal alterations qualitatively resemble those in phrenic motor nerves but do
not culminate in the loss of myelinated fibers. We further show that the pmn
mutation decreases the level of TBCE, impedes microtubule polymerization in
dorsal root ganglion (DRG) neurons and causes progressive loss of microtubules in
large and small caliber suralis axons. Live imaging of axonal transport using GFP
tagged tetanus toxin C-fragment (GFP-TTC) demonstrates defects in microtubule
based transport in pmn DRG neurons, providing a potential explanation for the
axonal alterations in sensory nerves. This study unravels sensory neuropathy as a
pathological feature of mouse pmn, and discusses the potential contribution of
cytoskeletal defects to sensory neuropathy in human motor neuron disease.
PMID- 27488539
TI - Silence of MACC1 decreases cell migration and invasion in human malignant
melanoma through inhibiting the EMT.
AB - Metastasis-associated colon cancer 1 (MACC1) has been demonstrated to promote
metastasis of several cancers via regulating epithelial-mesenchymal transition
(EMT). However, its biological behavior in human malignant melanoma remains
unclear. In this study, MACC1 downregulation was established in two melanoma cell
lines (A375 and G361 cells) using RNA interference, as confirmed by quantitative
real time PCR (qRT-PCR) and Western blot analysis. Subsequently, we investigated
the effects of MACC1 silencing on cell mobility, migration and invasion using
scratch wound and Transwell assays. Our results indicated that knockdown of MACC1
significantly suppressed cell migration and invasion ability of both melanoma
cell lines. Moreover, downregulation of MACC1 upregulated E-cadherin, N-cadherin
and Vimentin, as confirmed by qRT-PCR, Western blot and immunofluorescent
Staining analysis. These findings suggest MACC1 might serve as a new molecular
target for the treatment of melanoma by a novel mechanism underlying the
metastasis of melanoma cells.
PMID- 27488540
TI - Effects of iron and carbon monoxide on Lachesis muta muta venom-mediated
degradation of plasmatic coagulation.
AB - Hypofibrinogenemia is an important clinical consequence following envenomation by
Lachesis muta muta, usually attenuated or prevented by administration of
antivenom. The venom of L. m. muta contains both a metalloproteinase
fibrinogenase and a serine protease thrombin-like enzyme, and exposure of
fibrinogen to iron (Fe) and carbon monoxide (CO) has been demonstrated to
decrease its catalysis by such enzymes. Using thrombelastographic analytical
techniques, it was determined that this venom displayed weak procoagulant effects
combined with fibrinogenolytic effects, and pretreatment of plasma with Fe and CO
markedly attenuated venom-mediated effects. Additional experiments involving
heparin exposure and varying calcium concentrations demonstrated that
modification of fibrinogen with Fe and CO in human plasma rendered fibrinogen not
recognizable to the fibrinogenolytic metalloproteinase but did not prevent
polymerization by the thrombin-like serine protease. Lastly, when venom was
exposed to CO in isolation and then placed in plasma, the fibrinogenase was
inhibited but the thrombin-like enzyme was not inhibited. In sum, utilizing
relatively facile modifications, we demonstrated with thrombelastography that Fe
and/or CO addition can protect human plasmatic coagulation from fibrinogenase
activity but not the effects of the thrombin-like activity of L. m. muta venom.
PMID- 27488542
TI - NEET: India's single exam for admission to medical school promises transparency
and quality.
PMID- 27488541
TI - [Complex regional pain syndrome following distal fractures of the radius :
Epidemiology, pathophysiological models, diagnostics and therapy].
AB - The complex regional pain syndrome (CRPS) still represents an incompletely
etiologically understood complication following fractures of the distal radius.
The incidence of CRPS following fractures of the distal radius varies between 1 %
and 37 %. Pathophysiologically, a complex interaction of inflammatory,
somatosensory, motor and autonomic changes is suspected, leading to a persistent
maladaptive response and sensitization of the central and peripheral nervous
systems with development of the corresponding symptoms. Decisive for the
diagnostics are a detailed patient medical history and a clinical hand surgical,
neurological and pain-related examination with confirmation of the Budapest
criteria. Among the types of apparatus used for diagnostics, 3-phase bone
scintigraphy and temperature measurement have a certain importance. A multimodal
therapy started as early as possible is the most promising approach for
successful treatment. As part of a multimodal rehabilitation the main focus of
therapy lies on pain relief and functional aspects.
PMID- 27488543
TI - Rufibacter ruber sp. nov., isolated from fragmentary rock.
AB - A red-pigmented, Gram-stain-negative, rod-shaped, aerobic bacterium, designated
strain CCM 8646T, was isolated from stone fragments in James Ross Island,
Antarctica. Strain CCM 8646T was able to grow from 10 to 40 degrees C, in the
presence of up to 1 % (w/v) NaCl and at pH 7.0-11.0. Analysis of the 16S rRNA
gene sequence placed strain CCM 8646T in the genus Rufibacter with the closest
relative being Rufibacter roseus H359T (97.07 % 16S rRNA gene sequence
similarity). The digital DNA-DNA hybridization values between strain CCM 8646T
and R. roseus H359T were low (21.30+/-2.34 %). The major quinone was menaquinone
MK-7. The polar lipids comprised phosphatidylethanolamine, an unknown
aminoglycolipid and six unknown polar lipids. The G+C content of strain CCM 8646T
was 51.54 mol%. On the basis of phenotypic, chemotaxonomic and genotyping
results, strain CCM 8646T is considered to represent a novel species within the
genus Rufibacter, for which the name Rufibacter ruber sp. nov. is proposed. The
type strain is CCM 8646T (=LMG 29438T).
PMID- 27488545
TI - Age-related differences in trunk muscle reflexive behaviors.
AB - Reports of larger passive and similar intrinsic trunk stiffness in older vs.
younger populations suggest a diminishing demand for reflexive contributions of
trunk muscles to spinal stability with aging. It remains unclear, though, whether
such diminishing demands result in deterioration of trunk muscle reflexive
behaviors. A cross-sectional study was completed to assess age-related
differences in the latency and likelihood of trunk muscle reflexive responses to
sudden perturbations. Sixty healthy individuals, aged 20-70 years, were recruited
to form five equal-sized and gender-balanced age groups. Using a displacement
control, sudden perturbation paradigm, the latency and likelihood of trunk muscle
reflexive responses to sudden perturbations were estimated, and the influences of
age, gender, and level of effort (20% versus 30% of maximum voluntary exertion
MVE) were evaluated. There were no consistent age-related differences found in
any of the measures of trunk muscle reflexive behavior. However, the latency of
muscle response to perturbation was generally higher among older individuals, and
this difference was significant in the condition involving 30% MVE effort. With
an increase in level of effort (from 20% to 30% of MVE), there was a ~7% increase
in the latency of trunk muscle responses to anteriorly-directed perturbations as
well as ~ 15% (21%) decrease (increase) in response likelihood during anteriorly
(posteriorly) directed perturbations. Furthermore, the reflexive response
likelihood of trunk muscles was 28% (58%) larger (smaller) in female vs. male
participants during anteriorly (posteriorly) directed perturbations. Our results
did not, in general, support the hypothesis of an age-related decay in reflexive
trunk muscle behaviors. Larger reflexive responses were associated with lower
trunk intrinsic stiffness among females and during a lower level of effort,
suggesting a secondary role for reflexive responses in spinal stability. Such
secondary compensatory responses appear, however, to be consistent over a wide
age range.
PMID- 27488546
TI - Consensus documents and challenges in hypertension research.
PMID- 27488544
TI - Significant improvement of direct reprogramming efficacy of fibroblasts into
progenitor endothelial cells by ETV2 and hypoxia.
AB - BACKGROUND: Endothelial progenitor cell (EPC) transplantation is a promising
therapy for ischemic diseases such as ischemic myocardial infarction and hindlimb
ischemia. However, limitation of EPC sources remains a major obstacle. Direct
reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some
recent efforts successfully directly reprogrammed human fibroblasts into
functional EPCs; however, the procedure efficacy was low. This study therefore
aimed to improve the efficacy of direct reprogramming of human fibroblasts to
functional EPCs. METHODS: Human fibroblasts isolated from foreskin were directly
reprogrammed into EPCs by viral ETV2 transduction. Reprogramming efficacy was
improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen).
Phenotype analyses confirmed that single-factor ETV2 transduction successfully
reprogrammed dermal fibroblasts into functional EPCs. RESULTS: Hypoxia treatment
during the reprogramming procedure increased the efficacy of reprogramming from
1.21 +/- 0.61 % in normoxia conditions to 7.52 +/- 2.31 % in hypoxia conditions.
Induced EPCs in hypoxia conditions exhibited functional EPC phenotypes similar to
those in normoxia conditions, such as expression of CD31 and VEGFR2, and
expressed endothelial gene profiles similar to human umbilical vascular
endothelial cells. These cells also formed capillary-like networks in vitro.
CONCLUSION: Our study demonstrates a new simple method to increase the
reprogramming efficacy of human fibroblasts to EPCs using ETV2 and hypoxia.
PMID- 27488547
TI - Joint statement of the European Association for the Study of Obesity and the
European Society of Hypertension: obesity and heart failure.
AB - Obese individuals are more likely to develop heart failure. Yet, once heart
failure is established, the impact of overweight and obesity on prognosis and
survival is unclear. The purpose of this joint scientific statement of the
European Association for the Study of Obesity and the European Society of
Hypertension is to provide an overview on the current scientific literature on
obesity and heart failure in terms of prognosis, mechanisms, and clinical
management implications. Moreover, the document identifies open questions that
ought to be addressed. The need for more tailored weight management
recommendations in heart failure will be emphasized and, in line with the
emerging evidence, aims to distinguish between primary disease and secondary
outcome prevention. In the primary prevention of heart failure, it appears
prudent advising obese individuals to lose or achieve a healthy body weight,
especially in those with risk factors such as hypertension or type 2 diabetes.
However, there is no evidence from clinical trials to guide weight management in
overweight or obese patients with established heart failure. Prospective clinical
trials are strongly encouraged.
PMID- 27488548
TI - ECG left atrial abnormality: a marker of stroke prediction in hypertension.
PMID- 27488549
TI - Spironolactone versus renal nerve denervation for treatment of uncontrolled
resistant hypertension.
PMID- 27488550
TI - Impact of volunteer-related and methodology-related factors on the
reproducibility of brachial artery flow-mediated vasodilation: analysis of 672
individual repeated measurements.
AB - OBJECTIVES: Brachial artery flow-mediated dilation (FMD) is a popular technique
to examine endothelial function in humans. Identifying volunteer and
methodological factors related to variation in FMD is important to improve
measurement accuracy and applicability. METHODS: Volunteer-related and
methodology-related parameters were collected in 672 volunteers from eight
affiliated centres worldwide who underwent repeated measures of FMD. All centres
adopted contemporary expert-consensus guidelines for FMD assessment. After
calculating the coefficient of variation (%) of the FMD for each individual, we
constructed quartiles (n = 168 per quartile). Based on two regression models
(volunteer-related factors and methodology-related factors), statistically
significant components of these two models were added to a final regression model
(calculated as beta-coefficient and R). This allowed us to identify factors that
independently contributed to the variation in FMD%. RESULTS: Median coefficient
of variation was 17.5%, with healthy volunteers demonstrating a coefficient of
variation 9.3%. Regression models revealed age (beta = 0.248, P < 0.001),
hypertension (beta = 0.104, P < 0.001), dyslipidemia (beta = 0.331, P < 0.001),
time between measurements (beta = 0.318, P < 0.001), lab experience (beta =
0.133, P < 0.001) and baseline FMD% (beta = 0.082, P < 0.05) as contributors to
the coefficient of variation. After including all significant factors in the
final model, we found that time between measurements, hypertension, baseline FMD%
and lab experience with FMD independently predicted brachial artery variability
(total R = 0.202). CONCLUSION: Although FMD% showed good reproducibility, larger
variation was observed in conditions with longer time between measurements,
hypertension, less experience and lower baseline FMD%. Accounting for these
factors may improve FMD% variability.
PMID- 27488551
TI - Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated
with pediatric primary hypertension.
AB - OBJECTIVE: To identify novel biomarkers associated with pediatric primary
hypertension. METHODS: We recruited 350 participants (4-16 years). Anthropometric
parameters and aldosterone, plasma renin activity, cortisol, cortisone,
Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C
reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1
levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and
MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered
glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular
disease, primary aldosteronism and apparent mineralocorticoid excess syndrome
were excluded. RESULTS: In selected participants (n = 320), SBP was positively
correlated with BMI-SDS (r = 0.382, P < 0.001), HOMA-IR (r = 0.211, P < 0.001),
MMP-9 activity (r = 0.215, P < 0.001) and the cortisol/cortisone ratio (r =
0.231, P < 0.001). DBP showed similar correlations with these variables. No
correlation was observed with aldosterone or plasma renin activity. Participants
were categorized as hypertensive (n = 59) or nonhypertensive (n = 261). In the
univariate analysis, hypertensive patients had higher BMI-SDS (P < 0.001), HOMA
IR (P < 0.001), high-sensitivity C-reactive protein (P < 0.001), MMP-9 activity
(P < 0.001), plasminogen activator inhibitor type 1 (P < 0.001) and
cortisol/cortisone ratio (P < 0.001) than nonhypertensive patients. Multiple
regression analysis showed that the variables that remained associated with
hypertension were higher BMI-SDS [odds ratio (OR) = 3.74; 95% confidence interval
(CI) = 1.84-7.58], a higher cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98
7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). CONCLUSION:
We report that MMP-9 activity and the cortisol/cortisone ratio were higher in
pediatric primary hypertensive patients, and these associations were independent
of the effect of obesity. The potential role of these novel biomarkers in
predicting hypertension risk and blood pressure regulation warrants further
investigation.
PMID- 27488552
TI - Control of blood pressure and risk attenuation: a public health intervention in
rural Bangladesh, Pakistan, and Sri Lanka: feasibility trial results.
AB - BACKGROUND: High blood pressure (BP) is the leading attributable risk for
cardiovascular disease globally. There is little information on effective and
sustainable public health system strategies for managing hypertension in South
Asian countries. We conducted a feasibility study to gather preliminary data to
optimize BP-lowering strategies for a public health intervention in rural
communities in Bangladesh, Pakistan, and Sri Lanka. METHODS: A mixed method
feasibility study comprised a 3-month pre and postevaluation of a multicomponent
intervention (MCI), including BP screening and home health education by trained
government community health worker (CHW); providers trained in hypertension
management, and compensation of CHW for additional services. Checklists were used
to document care. Stakeholder interviews were also conducted. Individuals aged 40
years and above with high BP (systolic >=140 mmHg or diastolic >=90 mmHg based on
two readings from 2 separate days, or receiving antihypertensive medications)
were enrolled from rural communities in Bangladesh, Pakistan, and Sri Lanka. BP
was measured at baseline and 3 months postintervention. RESULTS: A total of 412
(90%) of the 454 eligible individuals were recruited. Of those recruited, 90%
received home health education session by trained CHWs, 80% were referred to
trained providers, of whom 83% completed the management checklist. A follow-up
rate of 95.6% was achieved. The mean SBP declined significantly by 4.5 mmHg 95%
confidence interval (2.3, 6.7) mmHg (P < 0.001) in the overall pooled analysis in
three countries; however, it varied among countries. BP decline was 10.5 mmHg
(8.1, 13.0 mmHg) (P < 0.001) in the pooled analysis of individuals with
uncontrolled hypertension at baseline, and was also significant each of the three
countries. All 98 stakeholders strongly supported upscaling the proposed MCI
strategies. CONCLUSION: The proposed MCI is feasible for implementation and
requires long-term, large-scale evaluation in the rural public health
infrastructure in South Asian countries to determine sustainability of health
system changes and BP control. If these long-term effects are confirmed, MCI may
be a long-term strategy for tackling rising rates of cardiovascular disease in
low-resourced countries.Clintrial.gov NCT02341651.
PMID- 27488553
TI - Applications might be subject to medical device regulation.
PMID- 27488554
TI - Reply.
PMID- 27488555
TI - Number-space associations without language: Evidence from preverbal human infants
and non-human animal species.
AB - It is well known that humans describe and think of numbers as being represented
in a spatial configuration, known as the 'mental number line'. The orientation of
this representation appears to depend on the direction of writing and reading
habits present in a given culture (e.g., left-to-right oriented in Western
cultures), which makes this factor an ideal candidate to account for the origins
of the spatial representation of numbers. However, a growing number of studies
have demonstrated that non-verbal subjects (preverbal infants and non-human
animals) spontaneously associate numbers and space. In this review, we discuss
evidence showing that pre-verbal infants and non-human animals associate small
numerical magnitudes with short spatial extents and left-sided space, and large
numerical magnitudes with long spatial extents and right-sided space. Together
this evidence supports the idea that a more biologically oriented view can
account for the origins of the 'mental number line'. In this paper, we discuss
this alternative view and elaborate on how culture can shape a core, fundamental,
number-space association.
PMID- 27488556
TI - Evolution of speech and evolution of language.
AB - Speech is the physical signal used to convey spoken language. Because of its
physical nature, speech is both easier to compare with other species' behaviors
and easier to study in the fossil record than other aspects of language. Here I
argue that convergent fossil evidence indicates adaptations for complex
vocalizations at least as early as the common ancestor of Neanderthals and modern
humans. Furthermore, I argue that it is unlikely that language evolved separately
from speech, but rather that gesture, speech, and song coevolved to provide both
a multimodal communication system and a musical system. Moreover, coevolution
must also have played a role by allowing both cognitive and anatomical
adaptations to language and speech to evolve in parallel. Although such a
coevolutionary scenario is complex, it is entirely plausible from a biological
point of view.
PMID- 27488557
TI - Why do animals differ in their susceptibility to geometrical illusions?
AB - In humans, geometrical illusions are thought to reflect mechanisms that are
usually helpful for seeing the world in a predictable manner. These mechanisms
deceive us given the right set of circumstances, correcting visual input where a
correction is not necessary. Investigations of non-human animals' susceptibility
to geometrical illusions have yielded contradictory results, suggesting that the
underlying mechanisms with which animals see the world may differ across species.
In this review, we first collate studies showing that different species are
susceptible to specific illusions in the same or reverse direction as humans.
Based on a careful assessment of these findings, we then propose several
ecological and anatomical factors that may affect how a species perceives
illusory stimuli. We also consider the usefulness of this information for
determining whether sight in different species might be more similar to human
sight, being influenced by contextual information, or to how machines process and
transmit information as programmed. Future testing in animals could provide new
theoretical insights by focusing on establishing dissociations between stimuli
that may or may not alter perception in a particular species. This information
could improve our understanding of the mechanisms behind illusions, but also
provide insight into how sight is subjectively experienced by different animals,
and the degree to which vision is innate versus acquired, which is difficult to
examine in humans.
PMID- 27488559
TI - Exploring electronic effects on the partitioning of actinides(iii) from
lanthanides(iii) using functionalised bis-triazinyl phenanthroline ligands.
AB - The first examples of 4,7-disubstituted 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8
tetrahydro-1,2,4-benzo-triazin-3-yl)-1,10-phenanthroline (CyMe4-BTPhen) ligands
are reported herein. Evaluating the kinetics, selectivity and stoichiometry of
actinide(iii) and lanthanide(iii) radiotracer extractions has provided a
mechanistic insight into the extraction process. For the first time, it has been
demonstrated that metal ion extraction kinetics can be modulated by backbone
functionalisation and a promising new CHON compliant candidate ligand with
enhanced metal ion extraction kinetics has been identified. The effects of 4,7
functionalisation on the equilibrium metal ion distribution ratios are far more
pronounced than those of 5,6-functionalisation. The complexation of Cm(iii) with
two of the functionalised ligands was investigated by TRLFS and, at equilibrium,
species of 1 : 2 [M : L] stoichiometry were observed exclusively. A direct
correlation between the ELUMO-EHOMO energy gap and metal ion extraction potential
is reported, with DFT studies reaffirming experimental findings.
PMID- 27488558
TI - The composite face illusion.
AB - Few findings in cognitive science have proved as influential as the composite
face effect. When the top half of one face is aligned with the bottom half of
another, and presented upright, the resulting composite arrangement induces a
compelling percept of a novel facial configuration. Findings obtained using
composite face procedures have contributed significantly to our understanding of
holistic face processing, the detrimental effects of face inversion, the
development of face perception, and aberrant face perception in clinical
populations. Composite paradigms continue to advance our knowledge of face
perception, as exemplified by their recent use for investigating the perceptual
mechanisms underlying dynamic face processing. However, the paradigm has been the
subject of intense scrutiny, particularly over the last decade, and there is a
growing sense that the composite face illusion, whilst easy to illustrate, is
deceptively difficult to measure and interpret. In this review, we provide a
focussed overview of the existing composite face literature, and identify six
priorities for future research. Addressing these gaps in our knowledge will aid
the evaluation and refinement of theoretical accounts of the illusion.
PMID- 27488560
TI - Expanding the phenotype of hawkinsinuria: new insights from response to N-acetyl
L-cysteine.
AB - Hawkinsinuria is a rare disorder of tyrosine metabolism that can manifest with
metabolic acidosis and growth arrest around the time of weaning off breast milk,
typically followed by spontaneous resolution of symptoms around 1 year of age.
The urinary metabolites hawkinsin, quinolacetic acid, and pyroglutamic acid can
aid in identifying this condition, although their relationship to the clinical
manifestations is not known. Herein we describe clinical and laboratory findings
in two fraternal twins with hawkinsinuria who presented with failure to thrive
and metabolic acidosis. Close clinical follow-up and laboratory testing revealed
previously unrecognized hypoglycemia, hypophosphatemia, combined hyperlipidemia,
and anemia, along with the characteristic urinary metabolites, including massive
pyroglutamic aciduria. Treatment with N-acetyl-L-cysteine (NAC) restored normal
growth and normalized or improved most biochemical parameters. The dramatic
response to NAC therapy supports the idea that glutathione depletion plays a key
role in the pathogenesis of hawkinsinuria.
PMID- 27488561
TI - Diagnostic and prognostic value of in vivo proton MR spectroscopy for Zellweger
syndrome spectrum patients.
AB - Defects in the biogenesis of peroxisomes cause a clinically and genetically
heterogeneous group of neurometabolic disorders, the Zellweger syndrome spectrum
(ZSS). Diagnosis predominantly is based on characteristic clinical symptoms, a
typical biochemical profile, as well as on identification of the molecular defect
in any of the 12 known human PEX genes. The diagnostic workup can be hindered if
the typical clinical symptoms are missing and predicting the clinical course of a
given patient is almost unfeasible. As a safe and noninvasive method to analyze
specific chemical compounds in localized brain regions, in vivo proton magnetic
resonance spectroscopy (MRS) can provide an indication in this diagnostic process
and may help predict the clinical course. However, to date, there are very few
reports on this topic. In this study, we performed localized in vivo proton MRS
without confounding contributions from T1- and T2-relaxation effects at 2 Tesla
in a comparably large group of seven ZSS patients. Patients' absolute metabolite
concentrations in cortical gray matter, white matter, and basal ganglia were
assessed and compared with age-matched control values. Our results confirm and
extend knowledge about in vivo MRS findings in ZSS patients. Besides affirmation
of nonspecific reduction of N-acetylaspartate + N-acetylaspartylglutamate (tNAA)
in combination with lipid accumulation as a diagnostic hint for this disease
group, the amount of tNAA loss seems to reflect disease burden and may prove to
be of prognostic value regarding the clinical course of an already diagnosed
patient.
PMID- 27488562
TI - Comparison of 10 single and stepped methods to identify frail older persons in
primary care: diagnostic and prognostic accuracy.
AB - BACKGROUND: Many instruments have been developed to identify frail older adults
in primary care. A direct comparison of the accuracy and prevalence of
identification methods is rare and most studies ignore the stepped selection
typically employed in routine care practice. Also it is unclear whether the
various methods select persons with different characteristics. We aimed to
estimate the accuracy of 10 single and stepped methods to identify frailty in
older adults and to predict adverse health outcomes. In addition, the methods
were compared on their prevalence of the identified frail persons and on the
characteristics of persons identified. METHODS: The Groningen Frailty Indicator
(GFI), the PRISMA-7, polypharmacy, the clinical judgment of the general
practitioner (GP), the self-rated health of the older adult, the Edmonton Frail
Scale (EFS), the Identification Seniors At Risk Primary Care (ISAR PC), the
Frailty Index (FI), the InterRAI screener and gait speed were compared to three
measures: two reference standards (the clinical judgment of a multidisciplinary
expert panel and Fried's frailty criteria) and 6-years mortality or long term
care admission. Data were used from the Dutch Identification of Frail Elderly
Study, consisting of 102 people aged 65 and over from a primary care practice in
Amsterdam. Frail older adults were oversampled. The accuracy of each instrument
and several stepped strategies was estimated by calculating the area under the
ROC-curve. RESULTS: Prevalence rates of frailty ranged from 14.8 to 52.9 %. The
accuracy for recommended cut off values ranged from poor (AUC = 0.556 ISAR-PC) to
good (AUC = 0.865 gait speed). PRISMA-7 performed best over two reference
standards, GP predicted adversities best. Stepped strategies resulted in lower
prevalence rates and accuracy. Persons selected by the different instruments
varied greatly in age, IADL dependency, receiving homecare and mood. CONCLUSION:
We found huge differences between methods to identify frail persons in
prevalence, accuracy and in characteristics of persons they select. A necessary
next step is to find out which frail persons can benefit from intervention before
case finding programs are implemented. Further evidence is needed to guide this
emerging clinical field.
PMID- 27488563
TI - Is rehabilitation post critical illness a new anti-inflammatory agent?
PMID- 27488564
TI - Stimulating therapy for obstructive sleep apnoea.
PMID- 27488565
TI - Sevelamer crystals in the bronchus: a case report.
PMID- 27488566
TI - A mixed methods protocol to evaluate the effect and cost-effectiveness of an
Integrated electronic Diagnosis Approach (IeDA) for the management of childhood
illnesses at primary health facilities in Burkina Faso.
AB - BACKGROUND: Burkina Faso introduced the Integrated Management of Childhood
Illnesses (IMCI) strategy in 2003. However, an evaluation conducted in 2013 found
that only 28 % of children were assessed for three danger signs as recommended by
IMCI, and only 15 % of children were correctly classified. About 30 % of children
were correctly prescribed with an antibiotic for suspected pneumonia or oral
rehydration salts (ORS) for diarrhoea, and 40 % were correctly referred. Recent
advances in information and communication technologies (ICT) and use of
electronic clinical protocols hold the potential to transform healthcare delivery
in low-income countries. However, no evidence is available on the effect of ICT
on adherence to IMCI. This paper describes the research protocol of a mixed
methods study that aims to measure the effect of the Integrated electronic
Diagnosis Approach innovation (an electronic IMCI protocol provided to nurses) in
two regions of Burkina Faso. METHODS/DESIGN: The study combines a stepped-wedge
trial, a realistic evaluation and an economic study in order to capture the
effect of the innovation after its introduction on the level of adherence, cost
and acceptability. DISCUSSION: The main challenge is to interconnect the three
substudies. In integrating outcome, process and cost data, we focus on three key
questions: (i) How does the effectiveness and the cost of the intervention vary
by type of health worker and type of health centre? (ii) What is the impact of
changes in the content, coverage and quality of the IeDA intervention on
adherence and cost-effectiveness? (iii) What mechanisms of change (including
costs) might explain the relationship between the IeDA intervention and
adherence? TRIAL REGISTRATION: Clinicaltrials.gov, NCT02341469 .
PMID- 27488568
TI - The Influence of Averageness on Adults' Perceptions of Attractiveness: The Effect
of Early Visual Deprivation.
AB - Adults who missed early visual input because of congenital cataracts later have
deficits in many aspects of face processing. Here we investigated whether they
make normal judgments of facial attractiveness. In particular, we studied whether
their perceptions are affected normally by a face's proximity to the population
mean, as is true of typically developing adults, who find average faces to be
more attractive than most other faces. We compared the judgments of facial
attractiveness of 12 cataract-reversal patients to norms established from 36
adults with normal vision. Participants viewed pairs of adult male and adult
female faces that had been transformed 50% toward and 50% away from their
respective group averages, and selected which face was more attractive.
Averageness influenced patients' judgments of attractiveness, but to a lesser
extent than controls. The results suggest that cataract-reversal patients are
able to develop a system for representing faces with a privileged position for an
average face, consistent with evidence from identity aftereffects. However, early
visual experience is necessary to set up the neural architecture necessary for
averageness to influence perceptions of attractiveness with its normal potency.
PMID- 27488567
TI - Evidence of non-response bias in the Press-Ganey patient satisfaction survey.
AB - BACKGROUND: Measures of patient satisfaction have gained prominence in recent
years as changes to the American health care system have led to the incorporation
of such metrics into reimbursement models. The response rate for widely-used
outpatient satisfaction metrics and variables influencing the probability of
survey nonresponse remain largely unknown. METHODS: We reviewed all unique adult
patients (16,779) who completed an outpatient encounter in the Department of
Orthopaedic surgery at our academic institution from 1/1/13 to 10/24/13. Survey
data was linked to each clinic visit, and patient factors including age, sex,
insurance type, zip code, and orthopaedic subspecialty visited were recorded. The
overall survey response rate was calculated. Logistic regression was performed,
and unadjusted and adjusted odds ratios of patients' probability of responding to
the Press-Ganey survey were calculated. RESULTS: Two thousand seven hundred sixty
two (16.5 %) of individuals completed a Press-Ganey patient satisfaction survey
and 14017 patients did not respond. For those patients considered responders, 906
patients (32.8 %) did not complete all the survey items. Among these 906
patients, the mean number of missing items was 2.24 (Standard Deviation SD:
2.19). Age, sex, insurance type, and orthopaedic subspecialty were all found to
be associated with the odds of responding to our patient satisfaction survey.
Advancing age increased the odds of responding to the survey (Adjusted Odds Ratio
(OR) = 3.396 for >=65 vs. 18-29, p < 0.001). Several variables were associated
with a decreased odds of survey response, and included male sex (Adjusted OR =
0.782 for Males vs. Females, p < 0.001), insurance type (Adjusted OR = 0.311 for
Medicaid/Self-Pay vs. Private), and subspecialty type (Adjusted OR = 0.623 for
Trauma vs. Adult Reconstruction). CONCLUSIONS: The response rate to the Press
Ganey Medical Practice Survey of outpatient satisfaction is low in an orthopaedic
outpatient population, and furthermore, is impacted by patient characteristics
such as age, sex, insurance type, and type of orthopaedic subspecialist
encountered. The findings of the present study should inform future non-response
weighting procedures in this area. More research is needed to assess non-response
bias-including follow-up studies of non-respondents-in order to more accurately
measure of patient satisfaction.
PMID- 27488569
TI - In-hospital measurement of left ventricular ejection fraction and one-year
outcomes in acute coronary syndromes: results from the IMMEDIATE Trial.
AB - BACKGROUND: In patients with acute coronary syndrome (ACS), reduced left
ventricular ejection fraction (LVEF) is a known marker for increased mortality.
However, the relationship between LVEF measured during index ACS hospitalization
and mortality and heart failure (HF) within 1 year are less well-defined.
METHODS: We performed a retrospective analysis of 445 participants in the
IMMEDIATE Trial who had LVEF measured by left ventriculography or echocardiogram
during hospitalization. RESULTS: Adjusting for age and coronary artery disease
(CAD) history, lower LVEF was significantly associated with 1-year mortality or
hospitalization for HF. For every 5 % LVEF reduction, the hazard ratio [HR] was
1.26 (95 % CI 1.15, 1.38, P < 0.001). Participants with LVEF < 40 % had higher
hazard of 1-year mortality or HF hospitalization than those with LVEF > 40 (HR
3.59; 95 % CI 2.05, 6.27, P < 0.001). The HRs for the association of LVEF with
the study outcomes were similar whether measured by left ventriculography or by
echocardiography, (respectively, HR 1.32; 95 % CI 1.15, 1.51 and 1.21; 95 % CI
1.106, 1.35, interaction P = 0.32) and whether done within 24 h or not within 24
h (respectively, HR 1.28; 95 % CI 1.10, 1.50 and 1.23; 95 % CI 1.10, 1.38,
interaction P = 0.67). CONCLUSIONS: Among patients with ACS, lower in-hospital
LVEF is associated with increased 1-year mortality or hospitalization for HF,
regardless of the method or timing of the LVEF assessment. This has prognostic
implications for clinical practice and suggests the possibility of using various
methods of LVEF determination in clinical research.
PMID- 27488570
TI - An intravoxel oriented flow model for diffusion-weighted imaging of the kidney.
AB - By combining intravoxel incoherent motion (IVIM) and diffusion tensor imaging
(DTI) we introduce a new diffusion model called intravoxel oriented flow (IVOF)
that accounts for anisotropy of diffusion and the flow-related signal. An IVOF
model using a simplified apparent flow fraction tensor (IVOFf ) is applied to
diffusion-weighted imaging of human kidneys. The kidneys of 13 healthy volunteers
were examined on a 3 T scanner. Diffusion-weighted images were acquired with six
b values between 0 and 800 s/mm(2) and 30 diffusion directions. Diffusivity and
flow fraction were calculated for different diffusion models. The Akaike
information criterion was used to compare the model fit of the proposed IVOFf
model to IVIM and DTI. In the majority of voxels the proposed IVOFf model with a
simplified apparent flow fraction tensor performs better than IVIM and DTI. Mean
diffusivity is significantly higher in DTI compared with models that account for
the flow-related signal. The fractional anisotropy of diffusion is significantly
reduced when flow fraction is considered to be anisotropic. Anisotropy of the
apparent flow fraction tensor is significantly higher in the renal medulla than
in the cortex region. The IVOFf model describes diffusion-weighted data in the
human kidney more accurately than IVIM or DTI. The apparent flow fraction in the
kidney proved to be anisotropic.
PMID- 27488572
TI - The SICAM-trial: evaluating the effect of spouses' involvement through case
management in older patients' fast-track programmes during and after total hip
replacement.
AB - AIM: The aim of this study was to evaluate the effect of spouses' involvement in
older patients' care trajectories, using case management as intervention in total
hip replacement through fast-track programmes. BACKGROUND: Patients need their
spouses to be involved in their fast-track programmes and this involvement is
often associated with improvements in patient outcomes. However, the effect of
spouses' involvement in older patients' fast-track programmes has not yet been
investigated. DESIGN: A two-group quasi-experimental design with pre-test and
repeated post-test measures was conducted in an orthopaedic ward of a Danish
Regional Hospital from February 2014-June 2015. Spouse-patient dyads were
initially recruited for the control group (n = 14), receiving usual care; dyads
for the intervention group (n = 15) were recruited afterwards, receiving case
management intervention elements before, during and after admission. METHODS:
Face-to-face interviews on questionnaires were conducted with spouses and
patients at baseline, 2 weeks and 3 months after discharge, measuring spouses'
caregiver satisfaction, difficulties and level of anxiety and patients'
functional and nutritional status, pain and level of depression. RESULTS: The
results showed that there were no differences between the groups with regard to
any of the outcome measures. However, statistically significant improvements were
found in the patient groups on functional status, pain and depression and in the
groups of spouses on caregiver satisfaction. CONCLUSION: The case management
intervention seemed to have an effect in patient and spousal groups; however,
this improvement could also have been caused by the effect of fast-track
treatment.
PMID- 27488573
TI - Living-donor parathyroid allotransplantation for therapy-refractory postsurgical
persistent hypoparathyroidism in a nontransplant recipient - three year results:
a case report.
AB - BACKGROUND: Therapy-refractory persistent hypoparathyroidism after extensive neck
surgery is a rare but severe complication. Parathyroid allotransplantation may
represent a definitive treatment option. CASE PRESENTATION: A 32-year old female
was referred to our hospital with intractable persistent hypocalcemia after neck
surgery for papillary thyroid cancer. Despite optimal medical treatment including
calcium and vitamin D supplementation and even hormonal replacement therapy
hypocalcemic symptoms failed to improve. The quality of life was considered very
low. In light of the unsuccessful medical therapy and the young age of the
patient parathyroid allotransplantation seemed an attractive treatment option to
restore normal calcium homeostasis despite of the need for immunosuppressive
therapy after the procedure. Therefore, we performed living-donor
allotransplantation of two healthy parathyroid glands to the recipient's left
forearm. The surgical intervention was successful. Neither the donor nor the
recipient showed any complications. In the postoperative course clinical symptoms
of hypocalcemia significantly improved whereas serum calcium and parathyroid
hormone (PTH) levels progressively increased into the normal range. Former
intense replacement therapy could be discontinued completely in a stepwise
fashion. To date, nearly three years after transplantation, the patient remains
asymptomatic with normal serum levels of calcium and PTH. CONCLUSION: Successful
living-donor parathyroid allotransplantation for postsurgical hypoparathyroidism
represents an innovative therapeutic strategy that could provide the definitive
treatment in those patients in which the disease is therapy-refractory. The
procedure can be justified even in nontransplant recipients. Retrieval of
parathyroid glands from healthy donors is feasible and safe.
PMID- 27488574
TI - A randomized crossover study to assess the pharmacokinetics of a novel
amphetamine extended-release orally disintegrating tablet in healthy adults.
AB - OBJECTIVES: In this pharmacokinetic (PK) study in healthy adults, we sought to:
(1) compare the PK properties of a novel amphetamine extended-release orally
disintegrating tablet formulation (Adzenys XR-ODTTM [AMP XR-ODT]) to a reference
extended-release mixed amphetamine salts (MAS ER) formulation and (2) assess the
effect of food on AMP XR-ODT. METHODS: Forty-two adults were enrolled in a single
dose, open-label, 3-period, 3-treatment, randomized crossover study and received
an 18.8-mg dose of AMP XR-ODT (fasted or fed) or equivalent dose (30 mg) of MAS
ER (fasted). Plasma samples were analyzed for d-and l-amphetamine. Maximum plasma
concentration (Cmax), time to maximum plasma concentration (Tmax), elimination
half-life (T1/2), area under the concentration-time curve from time zero to last
quantifiable concentration (AUClast), from time zero to infinity (AUCinf),
relevant partial AUCs, and weight-normalized clearance (CL/F/kg) were assessed.
The PK parameters were compared across treatments using an ANOVA. Safety was also
assessed. RESULTS: A total of 39 adults completed this study. The geometric mean
ratios (90% confidence interval [CI]) for AMP XR-ODT/MAS ER Cmax, AUC5-last,
AUClast, and AUCinf were within 80%-125% for both d-and l-amphetamine. The 90%
CIs for AUC0-5 were slightly below the 80%-125% range. When AMP XR-ODT was
administered with food, there was a slight decrease in the d-and l-amphetamine
Cmax and approximately a 2-hour delay in Tmax. The most common adverse events
reported (>5% of participants) were dry mouth, palpitations, nausea, dizziness,
headache, anxiety, and nasal congestion. CONCLUSIONS: AMP XR-ODT displayed a PK
profile similar to MAS ER, and no clinically relevant food effect was observed.
PMID- 27488575
TI - High-Intensity Drinking Among Young Adults in the United States: Prevalence,
Frequency, and Developmental Change.
AB - BACKGROUND: This study is the first to examine the developmental course of high
intensity drinking (i.e., consuming 10+ drinks in a row) across late adolescence
and the transition to adulthood. METHODS: National longitudinal data (N = 3,718)
from Monitoring the Future were used to examine trajectories of 10+ high
intensity drinking from age 18 through 25/26 overall and across sociodemographic
subgroups; results were compared with similar analysis of 5+ binge drinking
trajectories. RESULTS: Results document that 10+ drinkers consume not just a
greater quantity of alcohol on a given drinking occasion, but also engage in 5+
drinking more frequently than drinkers who do not report having 10 or more
drinks. Developmental patterns for 10+ and 5+ drinking were similar, with peak
frequencies reported at age 21/22. Greater peaks in both 10+ and 5+ drinking were
documented among men and among college attenders, compared with women and
nonattenders, respectively. However, there was a steeper decline in 10+ drinking
after age 21/22, indicating that risk for consumption of 10 or more drinks in a
row is more clearly focused on the early 20s. Patterns of developmental change in
both behaviors were driven largely by college students: No significant age
related change in 10+ drinking was observed among men and women who did not go to
college, and no significant age-related change in 5+ drinking was observed among
female nonattenders. CONCLUSIONS: Findings underscore the importance of
recognizing high-intensity drinkers as a unique high-risk group, and that college
attendance is associated with particularly strong peaks in the developmental
course of high-intensity drinking.
PMID- 27488577
TI - L1CAM as a prognostic marker in stage I endometrial cancer: a validation study.
AB - BACKGROUND: L1 cell adhesion molecule (L1CAM) overexpression has been reported to
be strongly associated with poor prognosis in early stage endometrial cancer
(EC). We aimed at the validation of L1CAM as a marker of poor prognosis in an
independent study population. METHODS: Patients with endometrioid EC FIGO stage
I, were treated at Oslo University Hospital between 2005 and 2012. L1CAM
expression was detected by immunohistochemistry with >10 % L1CAM staining defined
as positive. Risks of relapse and death were estimated as hazard ratios (HRs)
with 95 % confidence intervals (95 % CI). RESULTS: Of 450 patients, 388 (86 %)
were evaluable for L1CAM expression and 35 (9 %) were L1CAM positive. After
follow-up for a median time of 4.8 years (0.1-8.8), 33 (8 %) patients had
recurred. 6/35 (17 %) L1CAM positive patients relapsed compared to 27/353 (8 %)
L1CAM-negative patients. There were 7 (20 %) deaths in the L1CAM positive group,
and 34 (10 %) in the negative group. In multivariate analysis, controlled for age
and FIGO stage, L1CAM positivity was not significantly associated with the risk
of relapse (HR 2.08, 95 % CI: 0.85-5.10, p = 0.11) or death of all-cause (HR
1.81, 95 % CI: 0.79-4.11, p = 0.16). In patients who were not treated with
chemotherapy, L1CAM was significantly associated with risk of relapse (HR 2.9; 95
% CI: 1.08-7.56; p = 0.04). CONCLUSION: Our report confirms that L1CAM is
associated with a more aggressive tumortype and more distant relapses. The
overall recurrence rate in this population was low as were the absolute
differences between L1CAM positive and negative patients. In this independent
study sample, L1CAM failed to be a clinically relevant marker of poor prognosis
in stage I endometrioid endometrial carcinoma.
PMID- 27488578
TI - Transcriptomic analysis of mouse liver reveals a potential hepato-enteric
pathogenic mechanism in acute Toxoplasma gondii infection.
AB - BACKGROUND: Toxoplasma gondii is a worldwide spread pathogen which can infect all
tissues of its host. The transcriptomic responses of infected brain and spleen
have been reported. However, our knowledge of the global transcriptomic change in
infected liver is limited. Additionally, T. gondii infection represents a highly
dynamic process involving complex biological responses of the host at many
levels. Herein, we describe such processes at a global level by discovering gene
expression changes in mouse livers after acute infection with T. gondii ToxoDB#9
strain. RESULTS: Global transcriptomic analysis identified 2,758 differentially
expressed transcripts in infected liver, of which 1,356 were significantly
downregulated and 1,402 upregulated. GO and KEGG database analyses showed that
host immune responses were upregulated, while the metabolic-related
processes/pathways were downregulated, especially xenobiotic metabolism, fatty
acid metabolism, energy metabolism, and bile biosynthesis and secretion. The
metabolism of more than 800 chemical compounds including anti-Toxoplasma
prescribed medicines were predicted to be modulated during acute T. gondii
infection due to the downregulation of enzymes involved in xenobiotic metabolism.
CONCLUSIONS: To the best of our knowledge, this is the first global
transcriptomic analysis of mouse liver infected by T. gondii. The present data
indicate that during the early stage of liver infection, T. gondii can induce
changes in liver xenobiotic metabolism, upregulating inflammatory response and
downregulating hepatocellular PPAR signaling pathway, altering host bile
biosynthesis and secretion pathway; these changes could enhance host intestinal
dysbacteriosis and thus contribute to the pathological changes of both liver and
intestine of infected mice. These findings describe the biological changes in
infected liver, providing a potential mechanistic pathway that links hepatic and
intestinal pathologies to T. gondii infection.
PMID- 27488579
TI - A simple biomarker scoring matrix for early gastric cancer detection.
AB - Gastric cancer (GC) is a major cause of death in many parts of the world. While
90% of early GC is curable by resection, only about 5% of patients diagnosed in
the late stages survive beyond five years. This provides strong impetus to push
for early GC detection through the use of non-invasive biomarkers, before
metastatic complications arise. It is also of strong medical interest to identify
patients of the diffuse subtype at the earliest time possible, since the disease
variant progresses very rapidly and is associated with much higher mortality
rate. In this study, we compared quantitatively the gastric fluid proteome of 70
GC patients to 17 individuals with benign gastritis in search of potential
biomarkers that aid in GC diagnosis, prognosis and subtype stratification. We
report that as much as half of the gastric fluid proteome is subject to
regulation in diseased states, and propose a simple biomarker panel scoring
matrix for early GC detection with diagnostic sensitivity of 95.7%. We also
demonstrate as proof-of-concept that a digitised record generated with SWATH-MS
based on 380 protein abundance signatures from the gastric fluid could segregate
patients with diffuse-type GC.
PMID- 27488580
TI - Testosterone differentially regulates targets of lipid and glucose metabolism in
liver, muscle and adipose tissues of the testicular feminised mouse.
AB - Testosterone deficiency is commonly associated with obesity, metabolic syndrome,
type 2 diabetes and their clinical consequences-hepatic steatosis and
atherosclerosis. The testicular feminised mouse (non-functional androgen receptor
and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat
diet, whereas androgen-replete XY littermate controls do not. Testosterone
treatment ameliorates these effects, although the underlying mechanisms remain
unknown. We compared the influence of testosterone on the expression of
regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver,
abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice
displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle,
liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein
lipase required for fatty acid uptake was only reduced in subcutaneous adipose
tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous
tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is
associated with insulin resistance was increased in visceral adipose tissue and
cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and
liver tissue. Master regulator nuclear receptors involved in metabolism-Liver X
receptor expression was suppressed in all tissues except visceral adipose tissue,
whereas PPARgamma was lower in abdominal subcutaneous and visceral adipose tissue
and PPARalpha only in abdominal subcutaneous. Testosterone treatment improved the
expression (androgen receptor independent) of some targets but not all. These
exploratory data suggest that androgen deficiency may reduce the buffering
capability for glucose uptake and utilisation in abdominal subcutaneous and
muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill
and uptake of excess glucose and triglycerides into visceral adipose tissue,
liver and arterial walls.
PMID- 27488581
TI - FOXD3 controls pluripotency through modulating enhancer activity.
PMID- 27488582
TI - Liposomal Encapsulation Enzymes: From Medical Applications to Kinetic
Characteristics.
AB - Liposomes and nanoliposomes as small vesicles composed of phospholipid bilayer
(entrapping one or more hydrophilic or lipophilic components) have recently found
several potential applications in medicine and food industry. These vesicles may
protect the core materials from moisture, heat and other extreme conditions. They
may also provide controlled release of various bioactive agents, including food
ingredients at the right place and time. Potential applications of enzyme-loaded
liposomes are in the medical or biomedical field, particularly for the
enzymereplacement therapy, as well as cheese industry for production of
functional foods with improved health beneficial impacts on the consumer.
Encapsulation process has a recondite impact on enzymes. In fact, liposome
preparation techniques may alter the pH and temperature optima, affinity of the
enzyme to substrate (Km), and maximum rate of reaction (Vmax). In addition, in
this paper, the impact of process variables on the kinetic characteristics of
enzymes encapsulated in liposomes was investigated. Also, the effects of enzyme
entrapment in liposomes, prepared by different methods, on the catalytic
efficiency of enzyme, as well as its kinetic properties and stability compared to
native (free) enzymes has been reviewed.
PMID- 27488583
TI - Vaccine Ingredients: Components that Influence Vaccine Efficacy.
AB - Vaccination is defined as the administration of an antigenic material in order to
stimulate the immune system, leading to the development of adaptive immunity to a
pathogen. Vaccines can prevent or reduce morbidity from a vast number of
infections. This manuscript presents an analysis of vaccine types and vaccine
substances, concentrating on individual components including the active
ingredient, adjuvants, preservatives, stabilizers, inactivators, antibiotics,
diluents and other substances. While many papers have been published on
individual vaccine components, this review provides detail on a wide range of the
most commonly-used vaccine ingredients and components that have been tested in
clinical trials.
PMID- 27488584
TI - A Global View on Narcolepsy - A Review Study.
AB - Narcolepsy is an incurable neurological disorder when the brain is not able to
regulate a sleep and wakefulness cycle correctly. The affected person suddenly
falls asleep during the day or he/she suffers from excessive day sleepiness. In
addition, people may also suffer from cataplexy, hypnagogic hallucinations, sleep
paralysis, and disturbed nighttime sleep. The purpose of this review study is to
provide the latest information on both clinical and socioeconomic issues in the
field of narcolepsy treatment and emphasize its benefits and limitations. The
methodological approaches include a method of literature review of available
sources exploring the issue of narcolepsy, both from a global and specific
perspective point of view. On the basis of evaluation of these literature
sources, the researched issue is examined. The main benefits (e.g., new drugs are
being tested or non-invasive cognitive behavioral therapies are being applied)
and limitations (e.g., late diagnosis of the disease or lifelong and costly
treatment) of the treatment of narcolepsy are highlighted. The findings call for
more research in the field of the development of novel drugs reflecting
understanding of the neurological basis of narcolepsy and early diagnosis in
order to eliminate the symptoms of narcolepsy and prevent the development of this
disease.
PMID- 27488585
TI - A Review on Pharmacological Properties of Coumarins.
AB - The coumarin (benzopyran-2-one, or chromen-2-one) ring system, present in many
natural products, displays diverse pharmacological properties. It has attracted
the attention of chemists and medicinal chemists for decades. Many molecules
based on the coumarin ring system have been described utilizing innovative
synthetic methods. These synthetic routes have led to interesting analogues of
coumarins which possess pharmacological activities like anti-HIV, antimicrobial,
antiinflammatory, anticancer, anti-TB, anticonvulsant and MAO inhibitory
properties. Details of these studies, correlating structure with biological
activity are described in this review.
PMID- 27488586
TI - Research Progress of Mechanisms of Ceftriaxone Associated Nephrolithiasis.
AB - BACKGROUND: Urinary calculi can be caused by a variety of reasons, such as
metabolic abnormalities, urinary tract infection and obstruction. Certain
medications can induce urinary stone disease. Ceftriaxone, a third generation
cephalosporin with broad spectrum antibiotic activity, primarily eliminated by
the kidneys, has now been widely used for treatment of infection. It has been
long considered safe, especially in children. However, more and more cases about
ceftriaxone induced nephrolithiasis as a rare side effect have been reported.
CONCLUSION: This complication generally resolves spontaneously with cessation of
the drug. Severe nephrolithiasis can cause post renal acute renal failure (PARF).
There is limited information about how this complication develops, though high
doses and extended treatment periods are generally considered to be responsible.
Understanding the mechanisms would help the doctors to be aware of this rare
complication and respond with proper treatment. The primary goal of this review
is to discuss the possible mechanisms based on the most recent literatures.
PMID- 27488587
TI - Treatment interruption during radiation therapy: Experience at a single
institution in the Republic of Korea.
AB - AIM: Our study analyzed the frequency and causes of treatment interruption among
patients undergoing radiation therapy (RT). METHODS: A total of 1637 RT courses
in 1500 patients were reviewed from September 2009 to October 2013. A continuous
break over 7 days or a discontinuous break over 14 days was regarded as a
temporary break and RT under 80% of planned treatment was regarded as incomplete.
RESULTS: Two-hundred and twenty courses (13.4%) with treatment interruption were
identified. Half of the patients received RT with a definitive aim, and the other
half for palliative care. Completion after temporary break, near completion and
incompletion were noticed in 12.3%, 21.3%, and 66.4% of cases, respectively.
Among patients with a definite aim, thorax (19.2%) and abdomen (16.3%) had a
higher interruption rate. For brain and bone with a palliative aim, the frequency
of interruption was about 16%. Old age and worse performance negatively affected
interruption. The most common cause of treatment interruption was cancer
progression including death (30%) and the next was treatment-related side effects
(23.1%). CONCLUSION: About 13% of RT cases were interrupted. Two third of
patients received less than 80% of the planned RT. To improve RT completion rate,
multidirectional efforts are needed.
PMID- 27488588
TI - Comment on: "5-year outcomes of 1-stage gastric band removal and sleeve
gastrectomy".
PMID- 27488589
TI - Modified Arrow Flap Technique for Nipple Reconstruction.
PMID- 27488590
TI - Morphological Characterization of Acinar Cluster in Mouse Lung Using a Multiscale
based Segmentation Algorithm on Synchrotron Micro-CT Images.
AB - Understanding the three-dimensional morphology of pulmonary acini is essential
when exploring the biomechanics of respiratory function. In this study, we
characterized the morphology of individual acini and a cluster of acini stemming
from the same terminal conducting airway using a quantitative approach based on
the semi-automatic segmentation of synchrotron micro-CT images of mouse lung. The
volume and surface area of five clusters of mouse acini including 50 individual
acini were estimated based on the voxel and surface mesh of segmented acini at
FRC. The pathway length and width were estimated for one cluster including 15
acini based on the skeleton of segmented acini. The acinar volume was 0.09 +/-
0.07 mm(3) (mean +/- SD), and the surface area was 6.82 +/- 4.49 mm(2) , in
agreement with previous studies. The volume of the acinar clusters was 0.89 +/-
0.34 mm(3) , and the surface area was 68.18 +/- 17.66 mm(2) . The largest volume
acinus per cluster was found in the distal region of the terminal conducting
airway, and apparent respiratory bronchioles were observed only in large-volume
acini. The generation number of pathways per acinus was 8 +/- 2 (range: 6-12).
The pathway length at lower generations (generations 2-6) increased with the
generation number in a single cluster, while did not significantly change at
lower generations in some acinar groups. The pathway width increased with
increasing generation numbers. Our approach characterized the quantitative
morphology of pulmonary acinar clusters in mouse lung, and the results can be
used in further biomechanical simulation studies. Anat Rec, 299:1424-1434, 2016.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27488591
TI - Investigation of injection dose and camera integration time on quantifying
pharmacokinetics of a Cy5.5-GX1 probe with dynamic fluorescence imaging in vivo.
AB - The aim of this article is to investigate the influence of a tracer injection
dose (ID) and camera integration time (IT) on quantifying pharmacokinetics of
Cy5.5-GX1 in gastric cancer BGC-823 cell xenografted mice. Based on three
factors, including whether or not to inject free GX1, the ID of Cy5.5-GX1, and
the camera IT, 32 mice were randomly divided into eight groups and received 60
min dynamic fluorescence imaging. Gurfinkel exponential model (GEXPM) and
Lammertsma simplified reference tissue model (SRTM) combined with a singular
value decomposition analysis were used to quantitatively analyze the acquired
dynamic fluorescent images. The binding potential (Bp) and the sum of the
pharmacokinetic rate constants (SKRC) of Cy5.5-GX1 were determined by the SRTM
and EXPM, respectively. In the tumor region, the SKRC value exhibited an obvious
trend with change in the tracer ID, but the Bp value was not sensitive to it.
Both the Bp and SKRC values were independent of the camera IT. In addition, the
ratio of the tumor-to-muscle region was correlated with the camera IT but was
independent of the tracer ID. Dynamic fluorescence imaging in conjunction with a
kinetic analysis may provide more quantitative information than static
fluorescence imaging, especially for a priori information on the optimal ID of
targeted probes for individual therapy.
PMID- 27488592
TI - Factors influencing the perceived quality of clinical supervision of occupational
therapists in a large Australian state.
AB - BACKGROUND/AIM: Clinical supervision is important for effective health service
delivery, professional development and practice. Despite its importance there is
a lack of evidence regarding the factors that improve its quality. This study
aimed to investigate the factors that influence the quality of clinical
supervision of occupational therapists employed in a large public sector health
service covering mental health, paediatrics, adult physical and other practice
areas. METHODS: A mixed method, sequential explanatory study design was used
consisting of two phases. This article reports the quantitative phase (Phase One)
which involved administration of the Manchester Clinical Supervision Scale (MCSS
26) to 207 occupational therapists. RESULTS: Frequency of supervision sessions,
choice of supervisor and the type of supervision were found to be the predictor
variables with a positive and significant influence on the quality of clinical
supervision. Factors such as age, length of supervision and the area of practice
were found to be the predictor variables with a negative and significant
influence on the quality of clinical supervision. CONCLUSION: Factors that
influence the perceived quality of clinical supervision among occupational
therapists have been identified. High quality clinical supervision is an
important component of clinical governance and has been shown to be beneficial to
practitioners, patients and the organisation. Information on factors that make
clinical supervision effective identified in this study can be added to existing
supervision training and practices to improve the quality of clinical
supervision.
PMID- 27488593
TI - Meta-analysis of colorectal cancer follow-up after potentially curative
resection.
AB - BACKGROUND: After potentially curative resection of primary colorectal cancer,
patients may be monitored by measurement of carcinoembryonic antigen and/or CT to
detect asymptomatic metastatic disease earlier. METHODS: A systematic review and
meta-analysis was conducted to find evidence for the clinical effectiveness of
monitoring in advancing the diagnosis of recurrence and its effect on survival.
MEDLINE (Ovid), Embase, the Cochrane Library, Web of Science and other databases
were searched for randomized comparisons of increased intensity monitoring
compared with a contemporary standard policy after resection of primary
colorectal cancer. RESULTS: There were 16 randomized comparisons, 11 with
published survival data. More intensive monitoring advanced the diagnosis of
recurrence by a median of 10 (i.q.r. 5-24) months. In ten of 11 studies the
authors reported no demonstrable difference in overall survival. Seven RCTs,
published from 1995 to 2016, randomly assigned 3325 patients to a monitoring
protocol made more intensive by introducing new methods or increasing the
frequency of existing follow-up protocols versus less invasive monitoring. No
detectable difference in overall survival was associated with more intensive
monitoring protocols (hazard ratio 0.98, 95 per cent c.i. 0.87 to 1.11).
CONCLUSION: Based on pooled data from randomized trials published from 1995 to
2016, the anticipated survival benefit from surgical treatment resulting from
earlier detection of metastases has not been achieved.
PMID- 27488594
TI - Listeria monocytogenes Inhibits Serotonin Transporter in Human Intestinal Caco-2
Cells.
AB - Listeria monocytogenes is a Gram-positive bacterium that can cause a serious
infection. Intestinal microorganisms have been demonstrated to contribute to
intestinal physiology not only through immunological responses but also by
modulating the intestinal serotonergic system. Serotonin (5-HT) is a
neuromodulator that is synthesized in the intestinal epithelium and regulates the
whole intestinal physiology. The serotonin transporter (SERT), located in
enterocytes, controls intestinal 5-HT availability and therefore serotonin's
effects. Infections caused by L. monocytogenes are well described as being due to
the invasion of intestinal epithelial cells; however, the effect of L.
monocytogenes on the intestinal epithelium remains unknown. The main aim of this
work, therefore, was to study the effect of L. monocytogenes on SERT. Caco2/TC7
cell line was used as an enterocyte-like in vitro model, and SERT functional and
molecular expression assays were performed. Our results demonstrate that living
L. monocytogenes inhibits serotonin uptake by reducing SERT expression at the
brush border membrane. However, neither inactivated L. monocytogenes nor soluble
metabolites were able to affect SERT. The results also demonstrate that L.
monocytogenes yields TLR2 and TLR10 transcriptional changes in intestinal
epithelial cells and suggest that TLR10 is potentially involved in the inhibitory
effect observed on SERT. Therefore, L. monocytogenes, through TLR10-mediated SERT
inhibition, may induce increased intestinal serotonin availability and
potentially contributing to intestinal physiological changes and the initiation
of the inflammatory response.
PMID- 27488596
TI - TDP-43 pathology and cognition in ALS: A prospective clinicopathologic
correlation study.
AB - OBJECTIVE: Although a systematic spread of pathologic TDP-43 expression
throughout the CNS in amyotrophic lateral sclerosis (ALS) has been proposed, the
relationship between cognition and the extent and neuroanatomic distribution of
TDP-43 pathology has not received considerable attention. METHODS: We
investigated the association between cognitive functioning and the extent of TDP
43 pathology in postmortem CNS tissue from 18 patients with ALS stratified into 3
groups based on detailed prospective neuropsychological testing (cognitively not
impaired, n = 6; cognitively impaired, n = 6; ALS- frontotemporal dementia [FTD],
n = 6) and analyzed these cases for clinicopathologic correlations. RESULTS: Our
findings demonstrate a close relationship between cognition and the extent of TDP
43 pathology in non-primary motor areas with a striking difference between ALS
FTD and the 2 other cognitive groups. The specificity of our results was
underscored by 2 key findings: first, the absence of an Alzheimer pathology
effect, a common confounder in older patients; second, the lack of correlations
between the primary motor regions with the highest TDP-43 intensity and cognitive
status. CONCLUSIONS: Our data suggest a distinct dynamic of TDP-43 progression
and distribution in ALS-FTD in contrast to ALS without FTD.
PMID- 27488595
TI - Expression of p53, p16, cyclin D1, epidermal growth factor receptor and Notch1 in
patients with temporal bone squamous cell carcinoma.
AB - BACKGROUND: The aim of this study was to investigate the expression of p53, p16,
cyclin D1, epidermal growth factor receptor (EGFR) and Notch1 in temporal bone
squamous cell carcinoma (TBSCC) tissue samples by immunohistochemistry (IHC), and
to evaluate the association between these biomarkers and clinicopathological
features. METHODS: We performed a retrospective, single-institution review of 30
TBSCC patients treated with curative intent between April 2006 and March 2015.
All tissue samples were obtained from pretreatment biopsy specimens or surgical
specimens and using IHC staining. RESULTS: Ten patients were categorized as T1,
seven as T2, five as T3 and eight as T4. Nine patients had clinically positive
lymph node metastasis. The positive expression of p53 and EGFR was significantly
associated with T classification (P = 0.042 and P = 0.0039). EGFR expression was
significantly more frequent in patients with positive lymph node metastasis
compared with patients without node involvement (P = 0.017). In the analysis of
the association between protein expression by IHC staining and prognosis, the
positive expression of EGFR and Notch1 was significantly correlated with poor
survival outcomes in TBSCC (P = 0.015 and P = 0.025) CONCLUSION: Overexpression
of p53 and EGFR may be valuable biomarkers for identifying individuals at high
risk of developing tumors in TBSCC. Furthermore, the positive expression of EGFR
was significantly associated with poor survival outcome. Anti-EGFR therapy has
potential for use as the treatment modality of choice for advanced-stage TBSCC as
well as other head and neck squamous cell carcinomas.
PMID- 27488597
TI - Incident parkinsonism in older adults without Parkinson disease.
AB - OBJECTIVE: To determine the incidence of parkinsonism in community-dwelling older
adults without Parkinson disease. METHODS: Four parkinsonian signs were assessed
with a modified motor portion of the Unified Parkinson's Disease Rating Scale in
2,001 older adults without parkinsonism. We used Cox proportional hazards models
to determine the associations of age and sex with incident parkinsonism (2 or
more signs). We calculated the number of events per 1,000 person-years of
observation in 3 age strata. Next, we investigated several potential risk factors
for incident parkinsonism. Then, we examined longitudinal progression of
parkinsonism using discrete-time multistate Markov models. RESULTS: Average age
at baseline was 76.8 years (SD 7.62 years). During an average of 5 years of
follow-up, 964/2,001 (48.2%) developed parkinsonism. Age (hazard ratio [HR] 1.09,
95% confidence interval [CI] 1.08-1.10) but not male sex (HR 1.06, 95% CI 0.91
1.23) was associated with incident parkinsonism. The incidence of parkinsonism
per 1,000 person-years of follow-up was 36.0 for adults <75 years of age, 94.8
for those 75-84, and 160.5 for those 85 years or older. Depressive symptoms,
neuroticism, urinary incontinence, sleep complaints, and chronic health
conditions were associated with incident parkinsonism. Secondary analyses suggest
that risk factors are linked with incident parkinsonism via early motor signs of
parkinsonism and cognitive function. Transition modeling suggests that while
parkinsonism may fluctuate, it is progressive in most older adults and its risk
factors increase the odds of its progression. CONCLUSIONS: Parkinsonism is common
in older adults and increases with age. Identifying modifiable risk factors may
decrease the magnitude of this growing public health problem.
PMID- 27488598
TI - Lower microstructural integrity of brain white matter is related to higher
mortality.
AB - OBJECTIVE: To investigate the association of cerebral white matter
microstructural integrity with mortality. METHODS: We included 4,294 individuals,
free from stroke and dementia (mean age 63.6 years, 44% male) from the population
based Rotterdam Study (2006-2011). Diffusion-MRI was used to assess the
microstructural integrity of the white matter, both globally and for specific
white matter tracts. Fractional anisotropy and mean diffusivity were the measures
used to quantify white matter integrity. All-cause mortality and cause-specific
mortality was recorded with a median follow-up time of 5.4 and 4.6 years,
respectively. Cox regression models, adjusted for age, sex, APOE epsilon4 allele
carriership, cardiovascular risk factors, and macrostructural MRI changes, were
used to estimate hazard ratios. RESULTS: During the follow-up time, 216
participants (5.0%) died of all causes, 31 (0.7%) of cardiovascular causes, and
102 individuals (2.4%) died of noncardiovascular causes. Each SD decrease in
fractional anisotropy and each SD increase in mean diffusivity was associated
with a 1.37-fold (95% confidence interval: 1.20-1.57) and a 1.49-fold (95%
confidence interval: 1.28-1.75) higher hazard of all-cause mortality,
respectively. The associations were more prominent with cardiovascular mortality
than with noncardiovascular mortality. In tract-specific analyses, we observed
that association tracts were more prominently related to mortality. CONCLUSIONS:
Our findings suggest that impairments in cerebral white matter, even at early
stages, are not limited to adverse brain outcomes and they are related to
mortality, especially from cardiovascular causes.
PMID- 27488599
TI - A marked contrast between serotonergic and dopaminergic changes in dopa
responsive dystonia.
PMID- 27488600
TI - Lumpers or splitters: Evaluation and management of embolic stroke of undetermined
source.
PMID- 27488601
TI - Comparative analysis of C9orf72 and sporadic disease in an ALS clinic population.
AB - OBJECTIVE: We investigated whether the C9orf72 expansion mutation in patients
with amyotrophic lateral sclerosis (ALS) is associated with unique demographic
and clinical features. METHODS: Between 2001 and 2015, approximately half of all
patients attending the Emory ALS Clinic agreed to donate DNA for research. This
research cohort of 781 patients was screened for the C9orf72 expansion, and
demographic and clinical data were compared between those with and without the
C9orf72 mutation. For mutation carriers without a family history of ALS, we
sought further family history of dementia and other non-ALS neurodegenerative
diseases in first-degree relatives. RESULTS: The C9orf72 expansion was identified
in 61 patients (7.8%). Compared to those without the expansion mutation, these
patients did not differ in race, age, or site of onset. As expected, C9orf72
patients were more likely to have a family history of ALS (59% vs 7.9%) and to
present with comorbid frontotemporal dementia (FTD) (14.8% vs 1.7%). Survival was
shorter in patients with the expansion (log-rank chi(2)[1] = 45.323, p < 0.001).
Further investigation in 28 patients initially categorized as having no known
family history of ALS identified a family history of dementia in 16 cases; 6 of
these had characteristics suggestive of FTD. CONCLUSIONS: Comparing the C9orf72
ALS population to the general ALS population, there were no differences in race,
age at onset, or proportion of patients with bulbar onset disease. Differences
identified in patients with the C9orf72 mutation included shortened survival and
an equal proportion of men and women. In addition, we found that assessing family
history for dementia may identify other family members likely to be carrying the
C9orf72 expansion, reduce the number of sporadic cases, and thus increase our
understanding of disease penetrance.
PMID- 27488602
TI - The value of transesophageal echocardiography for embolic strokes of undetermined
source.
AB - OBJECTIVE: Our aim was to evaluate the diagnostic yield of transesophageal
echocardiography (TEE) in consecutive patients with ischemic stroke (IS)
fulfilling the diagnostic criteria of embolic strokes of undetermined source
(ESUS). METHODS: We prospectively evaluated consecutive patients with acute IS
satisfying ESUS criteria who underwent in-hospital TEE examination in 3 tertiary
care stroke centers during a 12-month period. We also performed a systematic
review and meta-analysis estimating the cumulative effect of TEE findings on
therapeutic management for secondary stroke prevention among different IS
subgroups. RESULTS: We identified 61 patients with ESUS who underwent
investigation with TEE (mean age 44 +/- 12 years, 49% men, median NIH Stroke
Scale score = 5 points [interquartile range: 3-8]). TEE revealed additional
findings in 52% (95% confidence interval [CI]: 40%-65%) of the study population.
TEE findings changed management (initiation of anticoagulation therapy,
administration of IV antibiotic therapy, and patent foramen ovale closure) in 10
(16% [95% CI: 9%-28%]) patients. The pooled rate of reported anticoagulation
therapy attributed to abnormal TEE findings among 3,562 acute IS patients
included in the meta-analysis (12 studies) was 8.7% (95% CI: 7.3%-10.4%). In
subgroup analysis, the rates of initiation of anticoagulation therapy on the
basis of TEE investigation did not differ (p = 0.315) among patients with
cryptogenic stroke (6.9% [95% CI: 4.9%-9.6%]), ESUS (8.1% [95% CI: 3.4%-18.1%]),
and IS (9.4% [95% CI: 7.5%-11.8%]). CONCLUSIONS: Abnormal TEE findings may
decisively affect the selection of appropriate therapeutic strategy in
approximately 1 of 7 patients with ESUS.
PMID- 27488603
TI - Role of sleep-disordered breathing and sleep-wake disturbances for stroke and
stroke recovery.
AB - BACKGROUND: Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD)
are highly prevalent in stroke patients. Recent studies suggest that they
represent both a risk factor and a consequence of stroke and affect stroke
recovery, outcome, and recurrence. METHODS: Review of literature. RESULTS:
Several studies have proven SDB to represent an independent risk factor for
stroke. Sleep studies in TIA and stroke patients are recommended in view of the
very high prevalence (>50%) of SDB (Class IIb, level of evidence B). Treatment of
obstructive SDB with continuous positive airway pressure is recommended given the
strength of the increasing evidence in support of a positive effect on outcome
(Class IIb, level of evidence B). Oxygen, biphasic positive airway pressure, and
adaptive servoventilation may be considered in patients with central SDB.
Recently, both reduced and increased sleep duration, as well as hypersomnia,
insomnia, and restless legs syndrome (RLS), were also suggested to increase
stroke risk. Mainly experimental studies found that SWD may in addition impair
neuroplasticity processes and functional stroke recovery. Treatment of SWD with
hypnotics and sedative antidepressants (insomnia), activating antidepressants or
stimulants (hypersomnia), dopaminergic drugs (RLS), and clonazepam (parasomnias)
are based on single case observations and should be used with caution.
CONCLUSIONS: SDB and SWD increase the risk of stroke in the general population
and affect short- and long-term stroke recovery and outcome. Current knowledge
supports the systematic implementation of clinical procedures for the diagnosis
and treatment of poststroke SDB and SWD on stroke units.
PMID- 27488604
TI - The MEssaging for Diabetes (MED) intervention improves short-term medication
adherence among low-income adults with type 2 diabetes.
AB - Adults with type 2 diabetes (T2DM) and low socioeconomic status (SES) have high
rates of medication nonadherence, and, in turn, suboptimal glycemic control
(hemoglobin A1c [HbA1c]). We tested the initial efficacy of a short message
service (SMS) text messaging and interactive voice response (IVR) intervention to
promote adherence among this high-risk group. Eighty low SES, diverse adults with
T2DM used the MEssaging for Diabetes (MED) SMS/IVR intervention for 3 months. We
used a pre-post single group design to explore adherence changes over 3 months,
and a quasi-experimental design to test the impact of MED on HbA1c among the
intervention group relative to a matched, archival control group. Compared to
baseline, adherence improved at one (AOR 3.88, 95 % CI 1.79, 10.86) and at 2
months (AOR 3.76, 95 % CI 1.75, 17.44), but not at 3 months. HbA1c remained
stable, with no differences at 3 months between the intervention group and the
control group. MED had a positive, short-term impact on adherence, which did not
translate to improvements in HbA1c. Future research should explore the longer
term impact of SMS/IVR interventions on the medication adherence of high risk
adults with T2DM.
PMID- 27488605
TI - A Direct Approach to In-Plane Stress Separation using Photoelastic Ptychography.
AB - The elastic properties of materials, either under external load or in a relaxed
state, influence their mechanical behaviour. Conventional optical approaches
based on techniques such as photoelasticity or thermoelasticity can be used for
full-field analysis of the stress distribution within a specimen. The circular
polariscope in combination with holographic photoelasticity allows the sum and
difference of principal stress components to be determined by exploiting the
temporary birefringent properties of materials under load. Phase stepping and
interferometric techniques have been proposed as a method for separating the in
plane stress components in two-dimensional photoelasticity experiments. In this
paper we describe and demonstrate an alternative approach based on photoelastic
ptychography which is able to obtain quantitative stress information from far
fewer measurements than is required for interferometric based approaches. The
complex light intensity equations based on Jones calculus for this setup are
derived. We then apply this approach to the problem of a disc under diametrical
compression. The experimental results are validated against the analytical
solution derived by Hertz for the theoretical displacement fields for an elastic
disc subject to point loading.
PMID- 27488606
TI - Multiple imputation of completely missing repeated measures data within person
from a complex sample: application to accelerometer data in the National Health
and Nutrition Examination Survey.
AB - The Physical Activity Monitor component was introduced into the 2003-2004
National Health and Nutrition Examination Survey (NHANES) to collect objective
information on physical activity including both movement intensity counts and
ambulatory steps. Because of an error in the accelerometer device initialization
process, the steps data were missing for all participants in several primary
sampling units, typically a single county or group of contiguous counties, who
had intensity count data from their accelerometers. To avoid potential bias and
loss in efficiency in estimation and inference involving the steps data, we
considered methods to accurately impute the missing values for steps collected in
the 2003-2004 NHANES. The objective was to come up with an efficient imputation
method that minimized model-based assumptions. We adopted a multiple imputation
approach based on additive regression, bootstrapping and predictive mean matching
methods. This method fits alternative conditional expectation (ace) models, which
use an automated procedure to estimate optimal transformations for both the
predictor and response variables. This paper describes the approaches used in
this imputation and evaluates the methods by comparing the distributions of the
original and the imputed data. A simulation study using the observed data is also
conducted as part of the model diagnostics. Finally, some real data analyses are
performed to compare the before and after imputation results. Published 2016.
This article is a U.S. Government work and is in the public domain in the USA.
PMID- 27488607
TI - Statins worsen glycemic control of T2DM in target LDL-c level and LDL-c reduction
dependent manners: a meta-analysis.
AB - OBJECTIVE: Recent studies demonstrated that a low target low-density lipoprotein
cholesterol (LDL-c) level, high LDL-c reduction and high dose of statin therapy
increased incident diabetes. This study aimed to explore how statin therapy
influences glycemic control in type 2 diabetes mellitus (T2DM). METHODS: Medline,
Embase, and Cochrane Central were searched for randomized control trials inT2DM.
Trials with target LDL-c levels of <=2.6 mmol/L or LDL-c reduction of >=30% were
analyzed. Then, we calculated mean differences in glycosylated hemoglobin (HbA1c)
and fasting blood glucose via stratified LDL-c level, relative LDL-c reduction
and statin dose. RESULTS: In total, trials involving 6,875 participants (3,619
statins, 3,256 controls) were included. Meta-analysis showed that detrimental
effect of intensive LDL-c lowering statin therapy on HbA1c (SMD 0.10%; 95% CI
0.05, 0.15; p = 0.000) was more severe than all statin trials analyzed together
(SMD 0.07%; 95% CI 0.02, 0.12; p = 0.005). Stratified analyses revealed that the
effects on HbA1c became increasingly significant as target LDL-c level decreased
and LDL-c reduction increased. Low baseline LDL-c and endpoint LDL-c levels were
risk factors involved in increasing HbA1c level during statin therapy.
CONCLUSIONS: Statin therapy worsens the glycemic control of T2DM in target LDL-c
level and LDL-c reduction dependent manners.
PMID- 27488608
TI - The association of the neighbourhood built environment with objectively measured
physical activity in older adults with and without lower limb osteoarthritis.
AB - BACKGROUND: This study examined the associations of objectively measured
neighbourhood built environment characteristics with objectively measured
physical activity (PA) in older people with and without lower limb osteoarthritis
(LLOA), and assessed whether these relationships differ between both groups.
METHODS: Data from the Dutch component of the European Project on OSteoArthritis
were used. American College of Rheumatology classification criteria were used to
diagnose LLOA (knee and/or hip osteoarthritis). Daily average time spent on total
PA and separate PA intensity categories, including light PA, low-light PA, high
light PA, and moderate to vigorous PA, were measured using Actigraph GT3X
accelerometers. Geographic Information Systems were used to measure street
connectivity (number of street connections per km(2)) and distances (in km) to
resources (health care resources, retail resources, meeting places, and public
transport) within neighbourhoods. Multiple Linear Regression Analyses were used
to examine the associations between measures of the neighbourhood built
environment and PA, adjusted for several confounders. RESULTS: Of all 247
participants (66-85 years), 41 (16.6 %) had LLOA. The time spent on any PA did
not differ significantly between participants with and without LLOA (LLOA: Mean =
268.3, SD = 83.3 versus non-LLOA: Mean = 275.8, SD = 81.2; p = 0.59). In the full
sample, no measures of the neighbourhood built environment were statistically
significantly associated with total PA. Larger distances to specific health care
resources (general practice and physiotherapist) and retail resources
(supermarket) were associated with more time spent on PA in older people with
LLOA than in those without LLOA. In particular, the associations of light and
high-light PA with distances to these specific resources were stronger in
participants with LLOA compared to their counterparts without LLOA. CONCLUSIONS:
Specific attributes of the neighbourhood built environment are more strongly
associated with PA in older people with LLOA than in those without LLOA.
Knowledge on the relationship between objectively measured neighbourhood
characteristics and PA in older people with and without LLOA could be used to
inform policymakers and city planners about adaptation of neighbourhoods and
their infrastructures to appropriately facilitate PA in healthy and functionally
impaired older adults.
PMID- 27488609
TI - Lutein attenuates oxidative stress markers and ameliorates glucose homeostasis
through polyol pathway in heart and kidney of STZ-induced hyperglycemic rat
model.
AB - PURPOSE: Lutein's role on chronic hyperglycemia-induced oxidative stress and
associated glucose homeostasis in heart and kidney is limited. Purpose of the
study is to investigate the effect of lutein on cardiac and renal polyol pathway
enzymes and oxidative stress markers under hyperglycemia-induced oxidative stress
condition using streptozotocin (STZ)-injected rat model. METHODS: STZ-induced
hyperglycemic (fasting blood glucose >=11 mM) male Wistar rats were divided into
two groups (n = 11/group). Group 1 received micellar lutein (39 nmol/day/rat) and
group 2 (negative control) received micelle without lutein for 8 weeks. A
separate group (no STZ injected) served as a positive control (n = 11/group).
Oral glucose tolerance test (OGTT), biweekly urine glucose and activities of
aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were assessed.
Activities of antioxidant enzymes and antioxidant level were also evaluated.
RESULTS: Lutein-administered hyperglycemic rats showed better glucose tolerance
as evidenced with OGTT and biweekly urine glucose when compared to negative
control. Activities of AR and SDH were decreased in heart and kidney of lutein
fed hyperglycemic rats. Also, they had significantly (p < 0.05) decreased
malondialdehyde levels (66, 34, and 33 %) and increased reduced glutathione level
(81, 18 and 92 %) in serum, heart and kidney, respectively. Altered antioxidant
enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase,
glutathione reductase and glutathione transferase were also affected in serum,
heart and kidney of lutein-fed diabetic group. CONCLUSION: Lutein prevented
cardiac and renal injury in STZ-induced hyperglycemic rats due to potential
amelioration of altered activities in polyol pathway and oxidative stress
markers.
PMID- 27488610
TI - The in vivo antineoplastic and therapeutic efficacy of troxerutin on rat
preneoplastic liver: biochemical, histological and cellular aspects.
AB - PURPOSE: Troxerutin (TXER), a trihydroxyethylated derivative of the natural
bioflavonoid rutin, abundantly found in tea, various fruits and vegetables, is
known to exhibit ample pharmacological properties. In the present investigation,
we examined the antineoplastic, therapeutic efficacy and furthermore the possible
mechanisms of action of TXER against NAFLD/NASH progression to
hepatocarcinogenesis. METHODS: The effect of TXER (12.5, 25 or 50 mg/kg b.w/day)
was evaluated on the nitrosodiethylamine (NDEA) model of hepatocarcinogenesis in
rats, after 16 weeks of oral treatment, with special focus on liver specific
enzymes, xenobiotic metabolizing enzymes, antioxidant status, lipid peroxidation
profile, DNA damage, fibrosis, cell proliferation and inflammatory status.
RESULTS: Administration of TXER to hepatocellular carcinoma-bearing rats restored
the enzyme activities and the hepatic architecture. Furthermore, TXER
significantly curtailed NDEA-induced DNA damage, cell proliferation,
inflammation, fibrosis and hepatic hyperplasia. CONCLUSION: This study provides
the evidence that troxerutin exerts a significant therapeutic effect against
liver cancer by modulating liver function enzymes, xenobiotic enzymes, oxidative
damage, inhibiting cell proliferation, suppressing inflammatory response and
induction of apoptosis.
PMID- 27488611
TI - Correlation between visit-to-visit and short-term blood pressure variability
calculated using different methods and glomerular filtration rate.
AB - The aim of this study was to explore the correlation between visit-to-visit and
short-term blood pressure variability (BPV), including systolic BPV (SBPV) and
diastolic BPV (DBPV), calculated using different methods, and the glomerular
filtration rate (GFR) in a late, middle-aged population. Using cluster sampling,
we randomly selected retired employees of the Kailuan Group who were ?60 years
and participated in a third health examination for 24-h ambulatory blood pressure
monitoring and inspection. Among the 3064 randomly selected observation subjects,
2464 were included based on the criteria. BPV was calculated using s.d.,
coefficient of variation (CV, s.d./Mean), variability independent of mean (VIM,
s.d./Meanx) and BPV ratio (BPVR, s.d. (SBPV)/s.d. (DBPV)). Multivariate linear
regression was used to analyse the correlation between estimated GFR (eGFR) and
BPV calculated using different methods. The mean age of 2464 subjects was 67.4+/
6.1 years, with 1667 male subjects (67.7%). A total of 2104 cases were included
in the visit-to-visit BPV group, and 1382 in the short-term BPV group. SBPV
calculated using different methods showed statistically significant increasing
trends for the SBP versus all s.d. and short-term BPVR. There was a significant,
positive correlation between the visit-to-visit and short-term BPV calculated
using different methods, which were all negatively correlated with eGFR (P<0.05).
Multivariate linear regression analysis showed that, with correction for possible
confounding factors, SBPV (24-h s.d., CV and VIM, and daytime CV and night time
CV) and all DBPV demonstrated negative linear relationships with eGFR (P<0.05).
PMID- 27488612
TI - The new Asian modified CKD-EPI equation leads to more accurate GFR estimation in
Chinese patients with CKD.
AB - OBJECTIVE: To verify whether the new Asian modified CKD-EPI equation improved the
performance of original one in determining GFR in Chinese patients with CKD.
METHOD: A well-designed paired cohort was set up. Measured GFR (mGFR) was the
result of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) dual plasma
sample clearance method. The estimated GFR (eGFR) was the result of the CKD-EPI
equation (eGFR1) and the new Asian modified CKD-EPI equation (eGFR2). The
comparisons were performed to evaluate the superiority of the eGFR2 in bias,
accuracy, precision, concordance correlation coefficient and the slope of
regression equation and measure agreement. RESULTS: A total of 195 patients were
enrolled and analyzed. The new Asian modified CKD-EPI equation improved the
performance of the original one in bias and accuracy. However, nearly identical
performance was observed in the respect of precision, concordance correlation
coefficient, slope of eGFR against mGFR and 95 % limit of agreement. In the
subgroup of GFR < 60 mL min-1/1.73 m2, the bias of eGFR1 was less than eGFR2 but
they have comparable precision and accuracy. In the subgroup of GFR > 60 mL min
1/1.73 m2, eGFR2 performed better than eGFR1 in terms of bias and accuracy.
CONCLUSION: The new Asian modified CKD-EPI equation can lead to more accurate GFR
estimation in Chinese patients with CKD in general practice, especially in the
higher GFR group.
PMID- 27488613
TI - Genetic analyses of herding traits in the Border Collie using sheepdog trial
data.
AB - The aim of this study was to evaluate the quality of the data provided from
sheepdog trials in Norway, estimate heritabilities, repeatabilities and genetic
correlations for the traits included in the trial and make recommendations on how
sheepdog trials best can be utilized in the breeding of Border Collies in Norway.
The analyses were based on test results from sheepdog trials carried out in
Norway from 1993 to 2012. A total of 45 732 records from 3841 Border Collies were
available, but after quality assurance only a third was left. The results
demonstrated little information in the data. Heritabilities varied between 0.010
and 0.056 with standard errors ranging from 0.010 to 0.023, while repeatabilities
ranged from 0.041 to 0.286. There is a need to assure the quality of data to
improve the information in the test results. We recommend adding new traits based
on the Herding Trait Characterization scheme evaluated in Sweden, and on traits
from the predatory motor pattern, regarded as common for all dogs. These new
traits may be scored across the elements that make up the current trial system,
which should be kept in place to stimulate participation in the genetic
evaluation scheme.
PMID- 27488614
TI - An ovarian bioreactor for in vitro culture of the whole bovine ovary: a
preliminary report.
AB - BACKGROUND: Improved cancer therapeutics and enhanced cancer survivorship have
emphasized the severe long-term side effects of chemotherapy. Specifically,
studies have linked many chemotherapy agents with primary ovarian insufficiency,
although an exact insult model has not yet been determined. To investigate and
ultimately solve this problem, a novel device for extended study of mammalian
ovaries in vitro was developed. METHODS: A bioreactor was fabricated for bovine
ovarian culture that provides intravascular delivery of media to the ovary
through isolation and cannulation of a main ovarian artery branch. Whole ovaries
were cultured in vitro using three methods: (1) continuously supplied fresh
culture media, (2) recirculated culture media, or (3) continuously supplied fresh
culture media supplemented with 500 nM doxorubicin for 24 or 48 h. TUNEL assay
was used to assess apoptotic cell percentages in the three groups as compared to
uncultured baseline ovaries. RESULTS: The ovary culture method was shown to
maintain cell viability by effectively delivering nutrient-enriched pH-balanced
media at a constant flow rate. Lower apoptosis observed in ovaries cultured in
continuously supplied fresh culture media illustrates that this culture device
and method are the first to sustain whole bovine ovary viability for 48 h.
Meanwhile, the increase in the percentage of cell apoptosis with doxorubicin
treatment indicates that the device can provide an alternative model for testing
chemotherapy and chemoprotection treatments to prevent primary ovarian
insufficiency in cancer patients. CONCLUSIONS: An ovarian bioreactor with
consistent culture media flow through an ovarian vasculature-assisted approach
maintains short-term whole bovine ovary viability.
PMID- 27488615
TI - The crystal structure of Clostridium perfringens SleM, a muramidase involved in
cortical hydrolysis during spore germination.
AB - Clostridium perfringens spores employ two peptidoglycan lysins to degrade the
spore cortex during germination. SleC initiates cortex hydrolysis to generate
cortical fragments that are degraded further by the muramidase SleM. Here, we
present the crystal structure of the C. perfringens S40 SleM protein at 1.8 A.
SleM comprises an N-terminal catalytic domain that adopts an irregular alpha/beta
barrel fold that is common to GH25 family lysozymes, plus a C-terminal
fibronectin type III domain. The latter is involved in forming the SleM dimer
that is evident in both the crystal structure and in solution. A truncated form
of SleM that lacks the FnIII domain shows reduced activity against spore sacculi
indicating that this domain may have a role in facilitating the position of
substrate with respect to the enzyme's active site. Proteins 2016; 84:1681-1689.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27488616
TI - [Mesenchymal tumors of the mediastinum].
AB - Mesenchymal neoplasms of the thymus and mediastinum account for only 2 % of
neoplasms of the mediastinum and are therefore very rare. With very few
exceptions the histology, immunohistochemistry and (based on current knowledge)
molecular biology of mediastinal soft tissue tumors are not different from their
counterparts in other organs. Characteristic features are more concerned with
clinical epidemiological and therapeutic aspects as well as the multitude of
possible differential diagnoses. With the exception of organ-specific tumors,
such as gastrointestinal stromal tumors (GIST), virtually all entities
encountered in peripheral soft tissues can also arise in the mediastinum. Primary
mediastinal soft tissue sarcomas (STS) must be distinguished from secondary
radiation-induced STS after irradiation, e. g. for breast cancer and Hodgkin's
lymphoma and from STS arising as somatic type malignancies in mediastinal germ
cell tumors.
PMID- 27488618
TI - Molecular diagnosis of African tick bite fever using eschar swabs in a traveller
returning from Tanzania.
AB - African tick bite fever is an emerging infectious disease among travellers caused
by the pathogen Rickettsia africae. Most travel-associated cases have been
reported from countries in southern Africa. So far it has rarely been reported
among travellers to eastern Africa and our patient is one of the first described
cases imported from Tanzania. A woman presented with fever, chills, headache,
myalgia and a rickettsial eschar on her ankle after returning from Tanzania. The
diagnosis of African tick bite fever is often based on clinical grounds due to a
lack of reliable diagnostic tests at commencement of symptoms. In this patient
direct molecular detection of R. africae was performed by PCR from a sample
obtained non-invasively with a swab from the rickettsial eschar. A positive PCR
result was achieved although the patient had already started antibiotic treatment
with doxycycline. In conclusion, this non-invasive method enables early diagnosis
of African tick bite fever by direct molecular detection of R. africae and might
improve the management of undifferentiated fever in travellers from Africa.
PMID- 27488617
TI - The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic
reprogramming dependent on NHE1 and associated with cell survival.
AB - Cancer cells display alterations in many cellular processes. One core hallmark of
cancer is the Warburg effect which is a glycolytic reprogramming that allows
cells to survive and proliferate. Although the contributions of environmental
contaminants to cancer development are widely accepted, the underlying mechanisms
have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic
aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a
human carcinogen according to the International Agency for Research on Cancer. In
addition to triggering apoptotic signals, B[a]P may induce survival signals, both
of which are likely to be involved in cancer promotion. We previously suggested
that B[a]P-induced mitochondrial dysfunctions, especially membrane
hyperpolarization, might trigger cell survival signaling in rat hepatic
epithelial F258 cells. Here, we further characterized these dysfunctions by
focusing on energy metabolism. We found that B[a]P promoted a metabolic
reprogramming. Cell respiration decreased and lactate production increased. These
changes were associated with alterations in the tricarboxylic acid cycle which
likely involve a dysfunction of the mitochondrial complex II. The glycolytic
shift relied on activation of the Na(+)/H(+) exchanger 1 (NHE1) and appeared to
be a key feature in B[a]P-induced cell survival related to changes in cell
phenotype (epithelial-to-mesenchymal transition and cell migration).
PMID- 27488619
TI - Commemorating John F. MacDonald and the Art of Being a Mentor.
AB - John F. MacDonald was a close friend and mentor whose life was ended far too soon
on April 22, 2014. To those who knew him, John was an endearing blend of fiery
Scotsman, compassionate socialist, dedicated family man, and tireless
investigator. Those close to him valued his loyalty and friendship, relished his
biting wit, and puzzled at his self-deprecating manner. His career spanned a
remarkable period of discovery from the early identification of excitatory amino
acid, to the molecular cloning and characterization of glutamate receptors and
the elucidation of mechanisms responsible for regulating their function. A true
pioneer in each of these areas, John's research has had a lasting impact on our
understanding of excitatory synaptic transmission and its plasticity. Our intent
in commemorating John's work is to focus on some notable discoveries that
highlight the impact and innovative aspects of John's work. In doing so, we also
wish to highlight just how greatly our understanding of the glutamate transmitter
systems has advanced since the late 1970s, when John first launched his
independent neuroscience career.
PMID- 27488620
TI - [Trauma of the lumbar spine and the thoracolumbar junction].
AB - CLINICAL/METHODICAL ISSUE: Patients who have experienced high energy trauma have
a particularly high risk of suffering from fractures of the thoracic and lumbar
spine. The detection of spinal injuries and the correct classification of
fractures before surgery are not only absolute requirements for the
implementation of appropriate surgical treatment but they are also decisive for
the choice of surgical procedure. STANDARD RADIOLOGICAL METHODS: By the
application of spiral computed tomography (CT) crucial additional information on
the morphology of the fracture can be gained in order to estimate the fracture
type and possibly the indications for specific surgical treatment options.
Magnetic resonance imaging (MRI) is ideally suited to provide valuable additional
information regarding injuries to the discoligamentous structures of the spine.
PERFORMANCE: Magerl et al. developed a comprehensive classification especially
for injuries of the thoracic and lumbar spine, which was adopted by the working
group for osteosynthesis (AO). This is based on a 2-pillar model of the spinal
column. The classification is based on the pathomorphological characteristics of
fractures recognizable by imaging. The injury pattern is of particular
importance. ACHIEVEMENTS: In spinal trauma a distinction is made between stable
and unstable fractures. The treatment of spinal injuries depends on the severity
of the overall injury pattern. PRACTICAL RECOMMENDATIONS: Besides adequate
initial treatment at the scene, a trauma CT should be immediately carried out in
order that no injuries are overlooked and to ensure a rapid decision on the
treatment procedure.
PMID- 27488621
TI - Increasing strength and conductivity of Cu alloy through abnormal plastic
deformation of an intermetallic compound.
AB - The precipitation strengthening of Cu alloys inevitably accompanies lowering of
their electric conductivity and ductility. We produced bulk Cu alloys arrayed
with nanofibers of stiff intermetallic compound through a precipitation mechanism
using conventional casting and heat treatment processes. We then successfully
elongated these arrays of nanofibers in the bulk Cu alloys to 400% of original
length without breakage at room temperature using conventional rolling process.
By inducing such an one-directional array of nanofibers of intermetallic compound
from the uniform distribution of fine precipitates in the bulk Cu alloys, the
trade-off between strength and conductivity and between strength and ductility
could be significantly reduced. We observed a simultaneous increase in electrical
conductivity by 1.3 times and also tensile strength by 1.3 times in this Cu alloy
bulk compared to the conventional Cu alloys.
PMID- 27488622
TI - Cryptic Caribbean species of Scorpaena (Actinopterygii: Scorpaeniformes)
suggested by cytogenetic and molecular data.
AB - Cytogenetic and molecular analyses enabled identification of two cytotypes among
individuals of the spotted scorpion fish Scorpaena plumieri from Margarita
Island, Venezuela. Cytotype 1 was characterized by 48 subtelo-acrocentric
chromosomes and fundamental number (number of chromosome arms; FN) equalled 48,
while cytotype 2 was characterized by two metacentric and 46 subtelo-acrocentric
chromosomes and FN was 50. These cytotypes also differed in the location of the
ribosomal gene clusters and in the distribution of the constitutive
heterochromatin. Moreover, fish from the cytotypes 1 and 2 were found to belong
to distinct mitochondrial lineages. The presence of two S. plumieri cytotypes
from two lineages separated by high genetic distance suggests that they
correspond to sympatric cryptic species.
PMID- 27488623
TI - Dual Perspectives.
PMID- 27488624
TI - Functional Heterogeneity in the Bed Nucleus of the Stria Terminalis.
AB - Early work stressed the differing involvement of the central amygdala (CeA) and
bed nucleus of the stria terminalis (BNST) in the genesis of fear versus anxiety,
respectively. In 2009, Walker, Miles, and Davis proposed a model of amygdala-BNST
interactions to explain these functional differences. This model became extremely
influential and now guides a new wave of studies on the role of BNST in humans.
Here, we consider evidence for and against this model, in the process
highlighting central principles of BNST organization. This analysis leads us to
conclude that BNST's influence is not limited to the generation of anxiety-like
responses to diffuse threats, but that it also shapes the impact of discrete
threatening stimuli. It is likely that BNST-CeA interactions are involved in
modulating responses to such threats. In addition, whereas current views
emphasize the contributions of the anterolateral BNST region in anxiety,
accumulating data indicate that the anteromedial and anteroventral regions also
play a critical role. The presence of multiple functional subregions within the
small volume of BNST raises significant technical obstacles for functional
imaging studies in humans.
PMID- 27488626
TI - Orientation Selectivity in the Retina: ON Cell Types and Mechanisms.
PMID- 27488627
TI - Presynaptic Deficits at Neuromuscular Junctions: A Specific Cause and Potential
Target of Axonal Neuropathy in Type 2 Charcot-Marie-Tooth Disease.
PMID- 27488625
TI - Contributions of the Central Extended Amygdala to Fear and Anxiety.
AB - It is widely thought that phasic and sustained responses to threat reflect
dissociable circuits centered on the central nucleus of the amygdala (Ce) and the
bed nucleus of the stria terminalis (BST), the two major subdivisions of the
central extended amygdala. Early versions of this hypothesis remain highly
influential and have been incorporated into the National Institute of Mental
Health Research Research Domain Criteria framework. However, new observations
encourage a different perspective. Anatomical studies show that the Ce and BST
form a tightly interconnected unit, where different kinds of threat-relevant
information can be integrated and used to assemble states of fear and anxiety.
Imaging studies in humans and monkeys show that the Ce and BST exhibit similar
functional profiles. Both regions are sensitive to a range of aversive
challenges, including uncertain or temporally remote threat; both covary with
concurrent signs and symptoms of fear and anxiety; both show phasic responses to
short-lived threat; and both show heightened activity during sustained exposure
to diffusely threatening contexts. Mechanistic studies demonstrate that both
regions can control the expression of fear and anxiety during sustained exposure
to diffuse threat. These observations compel a reconsideration of the central
extended amygdala's contributions to fear and anxiety and its role in
neuropsychiatric disease.
PMID- 27488628
TI - Zinc Selectively Blocks Neurosteroid-Sensitive Extrasynaptic deltaGABAA Receptors
in the Hippocampus.
AB - Zinc (Zn(2+)) is an essential cofactor in mammalian cells and neurons. Zn(2+) is
released from synaptic vesicles of certain nerve terminals in the hippocampus
during neuronal activity. Zn(2+) has been shown to inhibit synaptic GABAA
receptors and alter the hippocampal network excitability. However, the ability of
Zn(2+) to block extrasynaptic receptors remains unclear. Endogenous
neurosteroids, such as allopregnanolone (AP), regulate neuronal excitability by
allosteric activation of synaptic and extrasynaptic GABAA receptors.
Neurosteroids activate extrasynaptic deltaGABAA receptor-mediated tonic
inhibition in dentate gyrus granule cells (DGGCs), thereby contributing to the
regulation of downstream circuit excitability. Here we report a novel inhibitory
role of Zn(2+) at neurosteroid-sensitive, extrasynaptic deltaGABAA receptors by
electrophysiological recordings in DGGCs from adult mice. Zn(2+) displayed a
concentration-dependent, reversible noncompetitive blockade of AP-sensitive tonic
current in DGGCs (IC50, 16 MUm). Tonic current was fully blocked by Zn(2+), akin
to the GABAA receptor antagonist gabazine. Zn(2+) inhibition of tonic current was
lacking in DGGCs from delta-subunit knock-out mice. Moreover, AP-activated
synaptic receptor-mediated phasic currents were not affected by Zn(2+) Finally,
intrahippocampal infusion of Zn(2+) elicited rapid epileptiform activity and
significantly blocked the antiseizure activity of AP in the kindling model of
epilepsy. Thus, Zn(2+) inhibition of neurosteroid-sensitive, extrasynaptic GABAA
receptors in the hippocampus has direct implications in many brain
hyperexcitability conditions, such as seizures, epileptogenesis, and epilepsy.
Zn(2+) interactions may aid to further understand the physiology of extrasynaptic
GABAA receptors. SIGNIFICANCE STATEMENT: Zn(2+) is most abundant in the synaptic
vesicles of hippocampal mossy fibers. Zn(2+) release occurs with neuronal
excitation, including seizure events, and exerts powerful excitability effects in
the hippocampus circuits. Zn(2+) inhibits synaptic GABAA receptors, but its
interaction is less well appreciated at the extrasynaptic receptors, which
respond sensitively to endogenous neurosteroids. Here, we describe selective
functional blockade by Zn(2+) of neurosteroid-sensitive, extrasynaptic GABAA
receptors in the mouse hippocampus dentate gyrus, a key region associated with
epilepsy and memory disorders. By demonstrating that extracellular Zn(2+)
prevents neurosteroid augmentation of tonic current and protection against limbic
seizures, our findings provide novel implications of this potential antagonistic
interaction in a variety of neurological conditions.
PMID- 27488629
TI - Direction Selectivity in Drosophila Emerges from Preferred-Direction Enhancement
and Null-Direction Suppression.
AB - Across animal phyla, motion vision relies on neurons that respond preferentially
to stimuli moving in one, preferred direction over the opposite, null direction.
In the elementary motion detector of Drosophila, direction selectivity emerges in
two neuron types, T4 and T5, but the computational algorithm underlying this
selectivity remains unknown. We find that the receptive fields of both T4 and T5
exhibit spatiotemporally offset light-preferring and dark-preferring subfields,
each obliquely oriented in spacetime. In a linear-nonlinear modeling framework,
the spatiotemporal organization of the T5 receptive field predicts the activity
of T5 in response to motion stimuli. These findings demonstrate that direction
selectivity emerges from the enhancement of responses to motion in the preferred
direction, as well as the suppression of responses to motion in the null
direction. Thus, remarkably, T5 incorporates the essential algorithmic strategies
used by the Hassenstein-Reichardt correlator and the Barlow-Levick detector. Our
model for T5 also provides an algorithmic explanation for the selectivity of T5
for moving dark edges: our model captures all two- and three-point spacetime
correlations relevant to motion in this stimulus class. More broadly, our
findings reveal the contribution of input pathway visual processing, specifically
center-surround, temporally biphasic receptive fields, to the generation of
direction selectivity in T5. As the spatiotemporal receptive field of T5 in
Drosophila is common to the simple cell in vertebrate visual cortex, our stimulus
response model of T5 will inform efforts in an experimentally tractable context
to identify more detailed, mechanistic models of a prevalent computation.
SIGNIFICANCE STATEMENT: Feature selective neurons respond preferentially to
astonishingly specific stimuli, providing the neurobiological basis for
perception. Direction selectivity serves as a paradigmatic model of feature
selectivity that has been examined in many species. While insect elementary
motion detectors have served as premiere experimental models of direction
selectivity for 60 years, the central question of their underlying algorithm
remains unanswered. Using in vivo two-photon imaging of intracellular calcium
signals, we measure the receptive fields of the first direction-selective cells
in the Drosophila visual system, and define the algorithm used to compute the
direction of motion. Computational modeling of these receptive fields predicts
responses to motion and reveals how this circuit efficiently captures many useful
correlations intrinsic to moving dark edges.
PMID- 27488630
TI - A Neural Model of MST and MT Explains Perceived Object Motion during Self-Motion.
AB - When a moving object cuts in front of a moving observer at a 90 degrees angle,
the observer correctly perceives that the object is traveling along a
perpendicular path just as if viewing the moving object from a stationary vantage
point. Although the observer's own (self-)motion affects the object's pattern of
motion on the retina, the visual system is able to factor out the influence of
self-motion and recover the world-relative motion of the object (Matsumiya and
Ando, 2009). This is achieved by using information in global optic flow (Rushton
and Warren, 2005; Warren and Rushton, 2009; Fajen and Matthis, 2013) and other
sensory arrays (Dupin and Wexler, 2013; Fajen et al., 2013; Dokka et al., 2015)
to estimate and deduct the component of the object's local retinal motion that is
due to self-motion. However, this account (known as "flow parsing") is
qualitative and does not shed light on mechanisms in the visual system that
recover object motion during self-motion. We present a simple computational
account that makes explicit possible mechanisms in visual cortex by which self
motion signals in the medial superior temporal area interact with object motion
signals in the middle temporal area to transform object motion into a world
relative reference frame. The model (1) relies on two mechanisms (MST-MT feedback
and disinhibition of opponent motion signals in MT) to explain existing data, (2)
clarifies how pathways for self-motion and object-motion perception interact, and
(3) unifies the existing flow parsing hypothesis with established
neurophysiological mechanisms. SIGNIFICANCE STATEMENT: To intercept targets, we
must perceive the motion of objects that move independently from us as we move
through the environment. Although our self-motion substantially alters the motion
of objects on the retina, compelling evidence indicates that the visual system at
least partially compensates for self-motion such that object motion relative to
the stationary environment can be more accurately perceived. We have developed a
model that sheds light on plausible mechanisms within the visual system that
transform retinal motion into a world-relative reference frame. Our model reveals
how local motion signals (generated through interactions within the middle
temporal area) and global motion signals (feedback from the dorsal medial
superior temporal area) contribute and offers a new hypothesis about the
connection between pathways for heading and object motion perception.
PMID- 27488631
TI - Knowledge Acquisition during Exam Preparation Improves Memory and Modulates
Memory Formation.
AB - According to the schema-relatedness hypothesis, new experiences that make contact
with existing schematic knowledge are more easily encoded and remembered than new
experiences that do not. Here we investigate how real-life gains in schematic
knowledge affect the neural correlates of episodic encoding, assessing medical
students 3 months before and immediately after their final exams. Human
participants were scanned with functional magnetic resonance imaging while
encoding associative information that varied in relatedness to medical knowledge
(face-diagnosis vs face-name pairs). As predicted, improvements in memory
performance over time were greater for face-diagnosis pairs (high knowledge
relevance) than for face-name pairs (low knowledge-relevance). Improved memory
for face-diagnosis pairs was associated with smaller subsequent memory effects in
the anterior hippocampus, along with increased functional connectivity between
the anterior hippocampus and left middle temporal gyrus, a region important for
the retrieval of stored conceptual knowledge. The decrease in the anterior
hippocampus subsequent memory effect correlated with knowledge accumulation, as
independently assessed by a web-based learning platform with which participants
studied for their final exam. These findings suggest that knowledge accumulation
sculpts the neural networks associated with successful memory formation, and
highlight close links between knowledge acquired during studying and basic
neurocognitive processes that establish durable memories. SIGNIFICANCE STATEMENT:
In a sample of medical students, we tracked knowledge accumulation via a web
based learning platform and investigated its effects on memory formation before
and after participants' final medical exam. Knowledge accumulation led to
significant gains in memory for knowledge-related events and predicted a
selective decrease in hippocampal activation for successful memory formation.
Furthermore, enhanced functional connectivity was found between hippocampus and
semantic processing regions. These findings (1) demonstrate that knowledge
facilitates binding in the hippocampus by enhancing its communication with the
association cortices, (2) highlight close links between knowledge induced in the
real world and basic neurocognitive processes that establish durable memories,
and (3) exemplify the utility of combining laboratory-based cognitive
neuroscience research with real-world educational technology for the study of
memory.
PMID- 27488632
TI - Voluntary Running Exercise-Mediated Enhanced Neurogenesis Does Not Obliterate
Retrograde Spatial Memory.
AB - Running exercise (RE) improves cognition, formation of anterograde memories, and
mood, alongside enhancing hippocampal neurogenesis. A previous investigation in a
mouse model showed that RE-induced increased neurogenesis erases retrograde
memory (Akers et al., 2014). However, it is unknown whether RE-induced forgetting
is common to all species. We ascertained whether voluntary RE-induced enhanced
neurogenesis interferes with the recall of spatial memory in rats. Young rats
assigned to either sedentary (SED) or running exercise (RE) groups were first
subjected to eight learning sessions in a water maze. A probe test (PT) conducted
24 h after the final training session confirmed that animals in either group had
a similar ability for the recall of short-term memory. Following this, rats in
the RE group were housed in larger cages fitted with running wheels, whereas rats
in the SED group remained in standard cages. Animals in the RE group ran an
average of 78 km in 4 weeks. A second PT performed 4 weeks after the first PT
revealed comparable ability for memory recall between animals in the RE and SED
groups, which was evidenced through multiple measures of memory retrieval
function. The RE group displayed a 1.5- to 2.1-fold higher hippocampal
neurogenesis than SED rats. Additionally, both moderate and brisk RE did not
interfere with the recall of memory, although increasing amounts of RE
proportionally enhanced neurogenesis. In conclusion, RE does not impair memory
recall ability in a rat model despite substantially increasing neurogenesis.
SIGNIFICANCE STATEMENT: Running exercise (RE) improves new memory formation along
with an increased neurogenesis in the hippocampus. In view of a recent study
showing that RE-mediated increased hippocampal neurogenesis promotes
forgetfulness in a mouse model, we ascertained whether a similar adverse
phenomenon exists in a rat model. Memory recall ability examined 4 weeks after
learning confirmed that animals that had run a mean of 78 km and displayed a 1.5-
to 2.1-fold increase in hippocampal neurogenesis demonstrated similar proficiency
for memory recall as animals that had remained sedentary. Furthermore, both
moderate and brisk RE did not interfere with memory recall, although increasing
amounts of RE proportionally enhanced neurogenesis, implying that RE has no
adverse effects on memory recall.
PMID- 27488633
TI - Noninvasive Evaluation of Cellular Proliferative Activity in Brain Neurogenic
Regions in Rats under Depression and Treatment by Enhanced [18F]FLT-PET Imaging.
AB - Neural stem cells in two neurogenic regions, the subventricular zone and the
subgranular zone (SGZ) of the hippocampal dentate gyrus, can divide and produce
new neurons throughout life. Hippocampal neurogenesis is related to emotions,
including depression/anxiety, and the therapeutic effects of antidepressants, as
well as learning and memory. The establishment of in vivo imaging for
proliferative activity of neural stem cells in the SGZ might be used to diagnose
depression and to monitor the therapeutic efficacy of antidepressants. Positron
emission tomography (PET) imaging with 3'-deoxy-3'-[(18)F]fluoro-l-thymidine
([(18)F]FLT) has been studied to allow visualization of proliferative activity in
two neurogenic regions of adult mammals; however, the PET imaging has not been
widely used because of lower accumulation of [(18)F]FLT, which does not allow
quantitative assessment of the decline in cellular proliferative activity in the
SGZ under the condition of depression. We report the establishment of an enhanced
PET imaging method with [(18)F]FLT combined with probenecid, an inhibitor of drug
transporters at the blood-brain barrier, which can allow the quantitative
visualization of neurogenic activity in rats. Enhanced PET imaging allowed us to
evaluate reduced cell proliferation in the SGZ of rats with corticosterone
induced depression, and further the recovery of proliferative activity in rats
under treatment with antidepressants. This enhanced [(18)F]FLT-PET imaging
technique with probenecid can be used to assess the dynamic alteration of
neurogenic activity in the adult mammalian brain and may also provide a means for
objective diagnosis of depression and monitoring of the therapeutic effect of
antidepressant treatment. SIGNIFICANCE STATEMENT: Adult hippocampal neurogenesis
may play a role in major depression and antidepressant therapy. Establishment of
in vivo imaging for hippocampal neurogenic activity may be useful to diagnose
depression and monitor the therapeutic efficacy of antidepressants. Positron
emission tomography (PET) imaging has been studied to allow visualization of
neurogenic activity; however, PET imaging has not been widely used due to the
lower accumulation of the PET tracer in the neurogenic regions. Here, we
succeeded in establishing highly quantitative PET imaging for neurogenic activity
in adult brain with an inhibitor for drug transporter. This enhanced PET imaging
allowed evaluation of the decline of neurogenic activity in the hippocampus of
rats with depression and the recovery of neurogenic activity by antidepressant
treatment.
PMID- 27488634
TI - Interaction of ARC and Daxx: A Novel Endogenous Target to Preserve Motor Function
and Cell Loss after Focal Brain Ischemia in Mice.
AB - The aim of this study was to explore the signaling and neuroprotective effect of
transactivator of transcription (TAT) protein transduction of the apoptosis
repressor with CARD (ARC) in in vitro and in vivo models of cerebral ischemia in
mice. In mice, transient focal cerebral ischemia reduced endogenous ARC protein
in neurons in the ischemic striatum at early reperfusion time points, and in
primary neuronal cultures, RNA interference resulted in greater neuronal
susceptibility to oxygen glucose deprivation (OGD). TAT.ARC protein delivery led
to a dose-dependent better survival after OGD. Infarct sizes 72 h after 60 min
middle cerebral artery occlusion (MCAo) were on average 30 +/- 8% (mean +/- SD; p
= 0.005; T2-weighted MRI) smaller in TAT.ARC-treated mice (1 MUg
intraventricularly during MCAo) compared with controls. TAT.ARC-treated mice
showed better performance in the pole test compared with TAT.beta-Gal-treated
controls. Importantly, post-stroke treatment (3 h after MCAo) was still effective
in affording reduced lesion volume by 20 +/- 7% (mean +/- SD; p < 0.05) and
better functional outcome compared with controls. Delayed treatment in mice
subjected to 30 min MCAo led to sustained neuroprotection and functional behavior
benefits for at least 28 d. Functionally, TAT.ARC treatment inhibited DAXX-ASK1
JNK signaling in the ischemic brain. ARC interacts with DAXX in a CARD-dependent
manner to block DAXX trafficking and ASK1-JNK activation. Our work identifies for
the first time ARC-DAXX binding to block ASK1-JNK activation as an ARC-specific
endogenous mechanism that interferes with neuronal cell death and ischemic brain
injury. Delayed delivery of TAT.ARC may present a promising target for stroke
therapy. SIGNIFICANCE STATEMENT: Up to now, the only successful pharmacological
target of human ischemic stroke is thrombolysis. Neuroprotective pharmacological
strategies are needed to accompany therapies aiming to achieve reperfusion. We
describe that apoptosis repressor with CARD (ARC) interacts and inhibits DAXX and
proximal signals of cell death. In a murine stroke model mimicking human
malignant infarction in the territory of the middle cerebral artery, TAT.ARC
salvages brain tissue when given during occlusion or 3 h delayed with sustained
functional benefits (28 d). This is a promising novel therapeutic approach
because it appears to be effective in a model producing severe injury by
interfering with an array of proximal signals and effectors of the ischemic
cascade, upstream of JNK, caspases, and BIM and BAX activation.
PMID- 27488635
TI - Systemic Delivery of a Brain-Penetrant TrkB Antagonist Reduces Cocaine Self
Administration and Normalizes TrkB Signaling in the Nucleus Accumbens and
Prefrontal Cortex.
AB - Cocaine exposure alters brain-derived neurotrophic factor (BDNF) expression in
the brain. BDNF signaling through TrkB receptors differentially modulates cocaine
self-administration, depending on the brain regions involved. In the present
study, we determined how brain-wide inhibition of TrkB signaling affects cocaine
intake, the motivation for the drug, and reinstatement of drug taking after
extinction. To overcome the inability of TrkB ligands to cross the blood-brain
barrier, the TrkB antagonist cyclotraxin-B was fused to the nontoxic transduction
domain of the tat protein from human immunodeficiency virus type 1 (tat
cyclotraxin-B). Intravenous injection of tat-cyclotraxin-B dose-dependently
reduced cocaine intake, motivation for cocaine (as measured under a progressive
ratio schedule of reinforcement), and reinstatement of cocaine taking in rats
allowed either short or long access to cocaine self-administration. In contrast,
the treatment did not affect operant responding for a highly palatable sweet
solution, demonstrating that the effects of tat-cyclotraxin-B are specific for
cocaine reinforcement. Cocaine self-administration increased TrkB signaling and
activated the downstream Akt pathway in the nucleus accumbens, and had opposite
effects in the prefrontal cortex. Pretreatment with tat-cyclotraxin-B normalized
protein levels in these two dopamine-innervated brain regions. Cocaine self
administration also increased TrkB signaling in the ventral tegmental area, where
the dopaminergic projections originate, but pretreatment with tat-cyclotraxin-B
did not alter this effect. Altogether, our data show that systemic administration
of a brain-penetrant TrkB antagonist leads to brain region-specific effects and
may be a potential pharmacological strategy for the treatment of cocaine
addiction. SIGNIFICANCE STATEMENT: Brain-derived neurotrophic factor (BDNF)
signaling through TrkB receptors plays a well established role in cocaine
reinforcement. However, local manipulation of BDNF signaling yields divergent
effects, depending on the brain region, thereby questioning the viability of
systemic TrkB targeting for the treatment of cocaine use disorders. Our study
provides first-time evidence that systemic administration of a brain-penetrant
TrkB antagonist (tat-cyclotraxin-B) reduces several behavioral measures of
cocaine dependence, without altering motor performance or reinforcement by a
sweet palatable solution. In addition, although cocaine self-administration
produced opposite effects on TrkB signaling in the nucleus accumbens and
prefrontal cortex, tat-cyclotraxin-B administration normalized these cocaine
induced changes in both brain regions.
PMID- 27488636
TI - Two-Dimensional Cochlear Micromechanics Measured In Vivo Demonstrate Radial
Tuning within the Mouse Organ of Corti.
AB - The exquisite sensitivity and frequency discrimination of mammalian hearing
underlie the ability to understand complex speech in noise. This requires force
generation by cochlear outer hair cells (OHCs) to amplify the basilar membrane
traveling wave; however, it is unclear how amplification is achieved with sharp
frequency tuning. Here we investigated the origin of tuning by measuring sound
induced 2-D vibrations within the mouse organ of Corti in vivo Our goal was to
determine the transfer function relating the radial shear between the structures
that deflect the OHC bundle, the tectorial membrane and reticular lamina, to the
transverse motion of the basilar membrane. We found that, after normalizing their
responses to the vibration of the basilar membrane, the radial vibrations of the
tectorial membrane and reticular lamina were tuned. The radial tuning peaked at a
higher frequency than transverse basilar membrane tuning in the passive,
postmortem condition. The radial tuning was similar in dead mice, indicating that
this reflected passive, not active, mechanics. These findings were exaggerated in
Tecta(C1509G/C1509G) mice, where the tectorial membrane is detached from OHC
stereocilia, arguing that the tuning of radial vibrations within the hair cell
epithelium is distinct from tectorial membrane tuning. Together, these results
reveal a passive, frequency-dependent contribution to cochlear filtering that is
independent of basilar membrane filtering. These data argue that passive
mechanics within the organ of Corti sharpen frequency selectivity by defining
which OHCs enhance the vibration of the basilar membrane, thereby tuning the gain
of cochlear amplification. SIGNIFICANCE STATEMENT: Outer hair cells amplify the
traveling wave within the mammalian cochlea. The resultant gain and frequency
sharpening are necessary for speech discrimination, particularly in the presence
of background noise. Here we measured the 2-D motion of the organ of Corti in
mice and found that the structures that stimulate the outer hair cell
stereocilia, the tectorial membrane and reticular lamina, were sharply tuned in
the radial direction. Radial tuning was similar in dead mice and in mice lacking
a tectorial membrane. This suggests that radial tuning comes from passive
mechanics within the hair cell epithelium, and that these mechanics, at least in
part, may tune the gain of cochlear amplification.
PMID- 27488637
TI - Nalcn Is a "Leak" Sodium Channel That Regulates Excitability of Brainstem
Chemosensory Neurons and Breathing.
AB - The activity of background potassium and sodium channels determines neuronal
excitability, but physiological roles for "leak" Na(+) channels in specific
mammalian neurons have not been established. Here, we show that a leak Na(+)
channel, Nalcn, is expressed in the CO2/H(+)-sensitive neurons of the mouse
retrotrapezoid nucleus (RTN) that regulate breathing. In RTN neurons, Nalcn
expression correlated with higher action potential discharge over a more
alkalized range of activity; shRNA-mediated depletion of Nalcn hyperpolarized RTN
neurons, and reduced leak Na(+) current and firing rate. Nalcn depletion also
decreased RTN neuron activation by the neuropeptide, substance P, without
affecting pH-sensitive background K(+) currents or activation by a cotransmitter,
serotonin. In vivo, RTN-specific knockdown of Nalcn reduced CO2-evoked neuronal
activation and breathing; hypoxic hyperventilation was unchanged. Thus, Nalcn
regulates RTN neuronal excitability and stimulation by CO2, independent of direct
pH sensing, potentially contributing to respiratory effects of Nalcn mutations;
transmitter modulation of Nalcn may underlie state-dependent changes in breathing
and respiratory chemosensitivity. SIGNIFICANCE STATEMENT: Breathing is an
essential, enduring rhythmic motor activity orchestrated by dedicated brainstem
circuits that require tonic excitatory drive for their persistent function. A
major source of drive is from a group of CO2/H(+)-sensitive neurons in the
retrotrapezoid nucleus (RTN), whose ongoing activity is critical for breathing.
The ionic mechanisms that support spontaneous activity of RTN neurons are
unknown. We show here that Nalcn, a unique channel that generates "leak" sodium
currents, regulates excitability and neuromodulation of RTN neurons and CO2
stimulated breathing. Thus, this work defines a specific function for this
enigmatic channel in an important physiological context.
PMID- 27488638
TI - Feature-Selective Attentional Modulations in Human Frontoparietal Cortex.
AB - Control over visual selection has long been framed in terms of a dichotomy
between "source" and "site," where top-down feedback signals originating in
frontoparietal cortical areas modulate or bias sensory processing in posterior
visual areas. This distinction is motivated in part by observations that
frontoparietal cortical areas encode task-level variables (e.g., what stimulus is
currently relevant or what motor outputs are appropriate), while posterior
sensory areas encode continuous or analog feature representations. Here, we
present evidence that challenges this distinction. We used fMRI, a roving
searchlight analysis, and an inverted encoding model to examine representations
of an elementary feature property (orientation) across the entire human cortical
sheet while participants attended either the orientation or luminance of a
peripheral grating. Orientation-selective representations were present in a
multitude of visual, parietal, and prefrontal cortical areas, including portions
of the medial occipital cortex, the lateral parietal cortex, and the superior
precentral sulcus (thought to contain the human homolog of the macaque frontal
eye fields). Additionally, representations in many-but not all-of these regions
were stronger when participants were instructed to attend orientation relative to
luminance. Collectively, these findings challenge models that posit a strict
segregation between sources and sites of attentional control on the basis of
representational properties by demonstrating that simple feature values are
encoded by cortical regions throughout the visual processing hierarchy, and that
representations in many of these areas are modulated by attention. SIGNIFICANCE
STATEMENT: Influential models of visual attention posit a distinction between top
down control and bottom-up sensory processing networks. These models are
motivated in part by demonstrations showing that frontoparietal cortical areas
associated with top-down control represent abstract or categorical stimulus
information, while visual areas encode parametric feature information. Here, we
show that multivariate activity in human visual, parietal, and frontal cortical
areas encode representations of a simple feature property (orientation).
Moreover, representations in several (though not all) of these areas were
modulated by feature-based attention in a similar fashion. These results provide
an important challenge to models that posit dissociable top-down control and
sensory processing networks on the basis of representational properties.
PMID- 27488639
TI - Hepatocyte Growth Factor-c-MET Signaling Mediates the Development of Nonsensory
Structures of the Mammalian Cochlea and Hearing.
AB - The stria vascularis is a nonsensory structure that is essential for auditory
hair cell function by maintaining potassium concentration of the scala media.
During mouse embryonic development, a subpopulation of neural crest cell-derived
melanocytes migrates and incorporates into a subregion of the cochlear
epithelium, forming the intermediate cell layer of the stria vascularis. The
relation of this developmental process to stria vascularis function is currently
unknown. In characterizing the molecular differentiation of developing peripheral
auditory structures, we discovered that hepatocyte growth factor (Hgf) is
expressed in the future stria vascularis of the cochlear epithelium. Its receptor
tyrosine kinase, c-Met, is expressed in the cochlear epithelium and melanocyte
derived intermediate cells in the stria vascularis. Genetic dissection of HGF
signaling via c-MET reveals that the incorporation of the melanocytes into the
future stria vascularis of the cochlear duct requires c-MET signaling. In
addition, inactivation of either the ligand or receptor developmentally resulted
in a profound hearing loss at young adult stages. These results suggest a novel
connection between HGF signaling and deafness via melanocyte deficiencies.
SIGNIFICANCE STATEMENT: We found the roles of hepatocyte growth factor (HGF)
signaling in stria vascularis development for the first time and that lack of HGF
signaling in the inner ear leads to profound hearing loss in the mouse. Our
findings reveal a novel mechanism that may underlie human deafness DFNB39 and
DFNB97. Our findings reveal an additional example of context-dependent c-MET
signaling diversity, required here for proper cellular invasion developmentally
that is essential for specific aspects of auditory-related organogenesis.
PMID- 27488640
TI - A Subtype of Olfactory Bulb Interneurons Is Required for Odor Detection and
Discrimination Behaviors.
AB - Neural circuits that undergo reorganization by newborn interneurons in the
olfactory bulb (OB) are necessary for odor detection and discrimination,
olfactory memory, and innate olfactory responses, including predator avoidance
and sexual behaviors. The OB possesses many interneurons, including various types
of granule cells (GCs); however, the contribution that each type of interneuron
makes to olfactory behavioral control remains unknown. Here, we investigated the
in vivo functional role of oncofetal trophoblast glycoprotein 5T4, a regulator
for dendritic arborization of 5T4-expressing GCs (5T4 GCs), the level of which is
reduced in the OB of 5T4 knock-out (KO) mice. Electrophysiological recordings
with acute OB slices indicated that external tufted cells (ETCs) can be divided
into two types, bursting and nonbursting. Optogenetic stimulation of 5T4 GCs
revealed their connection to both bursting and nonbursting ETCs, as well as to
mitral cells (MCs). Interestingly, nonbursting ETCs received fewer inhibitory
inputs from GCs in 5T4 KO mice than from those in wild-type (WT) mice, whereas
bursting ETCs and MCs received similar inputs in both mice. Furthermore, 5T4 GCs
received significantly fewer excitatory inputs in 5T4 KO mice. Remarkably, in
olfactory behavior tests, 5T4 KO mice had higher odor detection thresholds than
the WT, as well as defects in odor discrimination learning. Therefore, the loss
of 5T4 attenuates inhibitory inputs from 5T4 GCs to nonbursting ETCs and
excitatory inputs to 5T4 GCs, contributing to disturbances in olfactory behavior.
Our novel findings suggest that, among the various types of OB interneurons, the
5T4 GC subtype is required for odor detection and discrimination behaviors.
SIGNIFICANCE STATEMENT: Neuronal circuits in the brain include glutamatergic
principal neurons and GABAergic interneurons. Although the latter is a minority
cell type, they are vital for normal brain function because they regulate the
activity of principal neurons. If interneuron function is impaired, brain
function may be damaged, leading to behavior disorder. The olfactory bulb (OB)
possesses various types of interneurons, including granule cells (GCs); however,
the contribution that each type of interneuron makes to the control of olfactory
behavior remains unknown. Here, we analyzed electrophysiologically and
behaviorally the function of oncofetal trophoblast glycoprotein 5T4, a regulator
for dendritic branching in OB GCs. We found that, among the various types of OB
interneuron, the 5T4 GC subtype is required for odor detection and odor
discrimination behaviors.
PMID- 27488641
TI - Reciprocal Control of Drinking Behavior by Median Preoptic Neurons in Mice.
AB - Stimulation of glutamatergic neurons in the subfornical organ drives drinking
behavior, but the brain targets that mediate this response are not known. The
densest target of subfornical axons is the anterior tip of the third ventricle,
containing the median preoptic nucleus (MnPO) and organum vasculosum of the
lamina terminalis (OVLT), a region that has also been implicated in fluid and
electrolyte management. The neurochemical composition of this region is complex,
containing both GABAergic and glutamatergic neurons, but the possible roles of
these neurons in drinking responses have not been addressed. In mice, we show
that optogenetic stimulation of glutamatergic neurons in MnPO/OVLT drives
voracious water consumption, and that optogenetic stimulation of GABAergic
neurons in the same region selectively reduces water consumption. Both
populations of neurons have extensive projections to overlapping regions of the
thalamus, hypothalamus, and hindbrain that are much more extensive than those
from the subfornical organ, suggesting that the MnPO/OVLT serves as a key link in
regulating drinking responses. SIGNIFICANCE STATEMENT: Neurons in the median
preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT)
are known to regulate fluid/electrolyte homeostasis, but few studies have
examined this issue with an appreciation for the neurochemical heterogeneity of
these nuclei. Using Cre-Lox genetic targeting of Channelrhodospin-2 in transgenic
mice, we demonstrate that glutamate and GABA neurons in the MnPO/OVLT
reciprocally regulate water consumption. Stimulating glutamatergic MnPO/OVLT
neurons induced water consumption, whereas stimulating GABAergic MnPO neurons
caused a sustained and specific reduction in water consumption in dehydrated
mice, the latter highlighting a heretofore unappreciated role of GABAergic MnPO
neurons in thirst regulation. These observations represent an important advance
in our understanding of the neural circuits involved in the regulation of
fluid/electrolyte homeostasis.
PMID- 27488642
TI - An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease
Affected Sheep.
AB - Sheep have large brains with human-like anatomy, making them a useful species for
studying brain function. Sleep homeostasis has not been studied in sheep. Here,
we establish correlates of sleep homeostasis in sheep through a sleep deprivation
experiment. We then use these correlates to elucidate the nature of sleep
deficits in a naturally occurring ovine model of neuronal ceroid lipofuscinosis
(NCL, Batten disease) caused by a mutation in CLN5 In humans, mutations in this
gene lead to cortical atrophy and blindness, as well as sleep abnormalities. We
recorded electroencephalograms (EEGs) from unaffected and early stage CLN5(-/-)
(homozygous, affected) sheep over 3 consecutive days, the second day being the
sleep deprivation day. In unaffected sheep, sleep deprivation led to increased
EEG delta (0.5-4 Hz) power during non-rapid eye movement (NREM) sleep, increased
time spent in the NREM sleep state, and increased NREM sleep bout length. CLN5(-/
) sheep showed comparable increases in time spent in NREM sleep and NREM sleep
bout duration, verifying the presence of increased sleep pressure in both groups.
Importantly, CLN5(-/-) sheep did not show the increase in NREM sleep delta power
seen in unaffected sheep. This divergent delta power response is consistent with
the known cortical degeneration in CLN5(-/-) sheep. We conclude that, whereas
sleep homeostasis is present in CLN5(-/-) sheep, underlying CLN5(-/-) disease
processes prevent its full expression, even at early stages. Such deficits may
contribute to early abnormalities seen in sheep and patients and warrant further
study. SIGNIFICANCE STATEMENT: Sleep abnormalities pervade most neurological
diseases, including the neuronal ceroid lipofuscinoses (NCLs). Here, we show
that, in an ovine model of a variant late-infantile NCL, there is abnormal
expression of sleep homeostasis. Whereas some sleep pressure correlates respond
to sleep deprivation, the strongest electroencephalogram (EEG) correlate of sleep
pressure, non-REM delta power, failed to increase. This highlights the relevance
of sleep deficits in this disease, in which the drive for sleep exists but the
underlying disease prevents its full expression. Sleep abnormalities could
contribute to early disease symptoms such as behavioral disorder and cognitive
decline. Our study also shows sleep homeostatic EEG correlates in sheep, opening
up new opportunities for studying sleep in a large social mammal with complex
human-like brain neuroanatomy.
PMID- 27488643
TI - Role of Binaural Temporal Fine Structure and Envelope Cues in Cocktail-Party
Listening.
AB - While conversing in a crowded social setting, a listener is often required to
follow a target speech signal amid multiple competing speech signals (the so
called "cocktail party" problem). In such situations, separation of the target
speech signal in azimuth from the interfering masker signals can lead to an
improvement in target intelligibility, an effect known as spatial release from
masking (SRM). This study assessed the contributions of two stimulus properties
that vary with separation of sound sources, binaural envelope (ENV) and temporal
fine structure (TFS), to SRM in normal-hearing (NH) human listeners. Target
speech was presented from the front and speech maskers were either colocated with
or symmetrically separated from the target in azimuth. The target and maskers
were presented either as natural speech or as "noise-vocoded" speech in which the
intelligibility was conveyed only by the speech ENVs from several frequency
bands; the speech TFS within each band was replaced with noise carriers. The
experiments were designed to preserve the spatial cues in the speech ENVs while
retaining/eliminating them from the TFS. This was achieved by using the
same/different noise carriers in the two ears. A phenomenological auditory-nerve
model was used to verify that the interaural correlations in TFS differed across
conditions, whereas the ENVs retained a high degree of correlation, as intended.
Overall, the results from this study revealed that binaural TFS cues, especially
for frequency regions below 1500 Hz, are critical for achieving SRM in NH
listeners. Potential implications for studying SRM in hearing-impaired listeners
are discussed. SIGNIFICANCE STATEMENT: Acoustic signals received by the auditory
system pass first through an array of physiologically based band-pass filters.
Conceptually, at the output of each filter, there are two principal forms of
temporal information: slowly varying fluctuations in the envelope (ENV) and
rapidly varying fluctuations in the temporal fine structure (TFS). The importance
of these two types of information in everyday listening (e.g., conversing in a
noisy social situation; the "cocktail-party" problem) has not been established.
This study assessed the contributions of binaural ENV and TFS cues for
understanding speech in multiple-talker situations. Results suggest that, whereas
the ENV cues are important for speech intelligibility, binaural TFS cues are
critical for perceptually segregating the different talkers and thus for solving
the cocktail party problem.
PMID- 27488644
TI - A Quantitative Analysis of Context-Dependent Remapping of Medial Frontal Cortex
Neurons and Ensembles.
AB - The frontal cortex has been implicated in a number of cognitive and motivational
processes, but understanding how individual neurons contribute to these processes
is particularly challenging as they respond to a broad array of events
(multiplexing) in a manner that can be dynamically modulated by the task context,
i.e., adaptive coding (Duncan, 2001). Fundamental questions remain, such as how
the flexibility gained through these mechanisms is balanced by the need for
consistency and how the ensembles of neurons are coherently shaped by task
demands. In the present study, ensembles of medial frontal cortex neurons were
recorded from rats trained to perform three different operant actions either in
two different sequences or two different physical environments. Single neurons
exhibited diverse mixtures of responsivity to each of the three actions and these
mixtures were abruptly altered by context/sequence switches. Remarkably, the
overall responsivity of the population remained highly consistent both within and
between context/sequences because the gains versus losses were tightly balanced
across neurons and across the three actions. These data are consistent with a
reallocation mixture model in which individual neurons express unique mixtures of
selectivity for different actions that become reallocated as task conditions
change. However, because the allocations and reallocations are so well balanced
across neurons, the population maintains a low but highly consistent response to
all actions. The frontal cortex may therefore balance consistency with
flexibility by having ensembles respond in a fixed way to task-relevant actions
while abruptly reconfiguring single neurons to encode "actions in context."
SIGNIFICANCE STATEMENT: Flexible modes of behavior involve performance of similar
actions in contextually relevant ways. The present study quantified the changes
in how rat medial frontal cortex neurons respond to the same actions when
performed in different task contexts (sequences or environments). Most neurons
altered the mixture of actions they were responsive to in different contexts or
sequences. Nevertheless, the responsivity profile of the ensemble remained fixed
as did the ability of the ensemble to differentiate between the three actions.
These mechanisms may help to contextualize the manner in which common events are
represented across different situations.
PMID- 27488645
TI - A Trial-by-Trial Window into Sensorimotor Transformations in the Human Motor
Periphery.
AB - The appearance of a novel visual stimulus generates a rapid stimulus-locked
response (SLR) in the motor periphery within 100 ms of stimulus onset. Here, we
recorded SLRs from an upper limb muscle while humans reached toward (pro-reach)
or away (anti-reach) from a visual stimulus. The SLR on anti-reaches encoded the
location of the visual stimulus rather than the movement goal. Further, SLR
magnitude was attenuated when subjects reached away from rather than toward the
visual stimulus. Remarkably, SLR magnitudes also correlated with reaction times
on both pro-reaches and anti-reaches, but did so in opposite ways: larger SLRs
preceded shorter latency pro-reaches but longer latency anti-reaches. Although
converging evidence suggests that the SLR is relayed via a tectoreticulospinal
pathway, our results show that task-related signals modulate visual signals
feeding into this pathway. The SLR therefore provides a trial-by-trial window
into how visual information is integrated with cognitive control in humans.
SIGNIFICANCE STATEMENT: The presentation of a visual stimulus elicits a trial-by
trial stimulus-locked response (SLR) on the human limb within 100 ms. Here, we
show that the SLR continues to reflect stimulus location even when subjects move
in the opposite direction (an anti-reach). Remarkably, the attenuation of SLR
magnitude reflected the cognitive control required to generate a correct anti
reach, with greater degrees of attenuation preceding shorter-latency anti-reaches
and no attenuation preceding error trials. Our results are strikingly similar to
neurophysiological recordings in the superior colliculus of nonhuman primates
generating anti-saccades, implicating the tectoreticulospinal pathway. Measuring
SLR magnitude therefore provides an unprecedented trial-by-trial opportunity to
assess the influence of cognitive control on the initial processing of a visual
stimulus in humans.
PMID- 27488646
TI - Thomas Boulton.
PMID- 27488647
TI - Laetoli footprints reveal bipedal gait biomechanics different from those of
modern humans and chimpanzees.
AB - Bipedalism is a key adaptation that shaped human evolution, yet the timing and
nature of its evolution remain unclear. Here we use new experimentally based
approaches to investigate the locomotor mechanics preserved by the famous
Pliocene hominin footprints from Laetoli, Tanzania. We conducted footprint
formation experiments with habitually barefoot humans and with chimpanzees to
quantitatively compare their footprints to those preserved at Laetoli. Our
results show that the Laetoli footprints are morphologically distinct from those
of both chimpanzees and habitually barefoot modern humans. By analysing
biomechanical data that were collected during the human experiments we, for the
first time, directly link differences between the Laetoli and modern human
footprints to specific biomechanical variables. We find that the Laetoli hominin
probably used a more flexed limb posture at foot strike than modern humans when
walking bipedally. The Laetoli footprints provide a clear snapshot of an early
hominin bipedal gait that probably involved a limb posture that was slightly but
significantly different from our own, and these data support the hypothesis that
important evolutionary changes to hominin bipedalism occurred within the past
3.66 Myr.
PMID- 27488648
TI - The evolution of eggshell cuticle in relation to nesting ecology.
AB - Avian eggs are at risk of microbial infection prior to and during incubation. A
large number of defence mechanisms have evolved in response to the severe costs
imposed by these infections. The eggshell's cuticle is an important component of
antimicrobial defence, and its role in preventing contamination by microorganisms
in domestic chickens is well known. Nanometer-scale cuticular spheres that reduce
microbial attachment and penetration have recently been identified on eggs of
several wild avian species. However, whether these spheres have evolved
specifically for antimicrobial defence is unknown. Here, we use comparative data
on eggshell cuticular structure and nesting ecology to test the hypothesis that
birds nesting in habitats with higher risk of infection (e.g. wetter and warmer)
are more likely to evolve cuticular nanospheres on their eggshells than those
nesting in less risky habitats. We found that nanostructuring, present in 54 of
296 analysed species, is the ancestral condition of avian eggshells and has been
retained more often in taxa that nest in humid infection-prone environments,
suggesting that they serve critical roles in antimicrobial egg defence.
PMID- 27488649
TI - Dispersal propensity, but not flight performance, explains variation in dispersal
ability.
AB - Enhanced dispersal ability may lead to accelerated range expansion and increased
rates of population establishment, thereby affecting population genetic structure
and evolutionary potential. Morphological, behavioural and physiological traits
that characterize dispersive individuals from residents are poorly understood for
many invertebrate systems, especially in non-polymorphic pterygote species. Here
we examined phenotypic differences between dispersal-prone and philopatric
individuals from repeated mark-release-recapture (MRR) experiments using an
invasive agricultural pest, Ceratitis capitata Comprehensive morphometric
assessment and subsequent minimal adequate modelling using an information
theoretic approach identified thorax mass : body mass ratio as a key predictor of
disperser flies under semi-natural conditions. Performance differences in flight
ability were then examined under controlled laboratory conditions to assess
whether greater thorax mass : body mass ratio was associated with enhanced flight
ability. The larger thorax : body mass ratio was associated with measurable
differences in mean flight duration, most predominantly in males, and also by
their willingness to disperse, scored as the number and duration of voluntary
flights. No other measures of whole-animal flight performance (e.g. mean and peak
vertical force, total or maximum flight duration) differed. Variation in
voluntary behaviour may result in significant alterations of movement behaviour
and realized dispersal in nature. This phenomenon may help explain intraspecific
variation in the dispersal ability of insects.
PMID- 27488650
TI - Pigmented anatomy in Carboniferous cyclostomes and the evolution of the
vertebrate eye.
AB - The success of vertebrates is linked to the evolution of a camera-style eye and
sophisticated visual system. In the absence of useful data from fossils,
scenarios for evolutionary assembly of the vertebrate eye have been based
necessarily on evidence from development, molecular genetics and comparative
anatomy in living vertebrates. Unfortunately, steps in the transition from a
light-sensitive 'eye spot' in invertebrate chordates to an image-forming camera
style eye in jawed vertebrates are constrained only by hagfish and lampreys
(cyclostomes), which are interpreted to reflect either an intermediate or
degenerate condition. Here, we report-based on evidence of size, shape,
preservation mode and localized occurrence-the presence of melanosomes (pigment
bearing organelles) in fossil cyclostome eyes. Time of flight secondary ion mass
spectrometry analyses reveal secondary ions with a relative intensity
characteristic of melanin as revealed through principal components analyses. Our
data support the hypotheses that extant hagfish eyes are degenerate, not
rudimentary, that cyclostomes are monophyletic, and that the ancestral vertebrate
had a functional visual system. We also demonstrate integument pigmentation in
fossil lampreys, opening up the exciting possibility of investigating colour
patterning in Palaeozoic vertebrates. The examples we report add to the record of
melanosome preservation in Carboniferous fossils and attest to surprising
durability of melanosomes and biomolecular melanin.
PMID- 27488651
TI - Parallel telomere shortening in multiple body tissues owing to malaria infection.
AB - Several studies have shown associations between shorter telomere length in blood
and weakened immune function, susceptibility to infections, and increased risk of
morbidity and mortality. Recently, we have shown that malaria accelerates
telomere attrition in blood cells and shortens lifespan in birds. However, the
impact of infections on telomere attrition in different body tissues within an
individual is unknown. Here, we tested whether malarial infection leads to
parallel telomere shortening in blood and tissue samples from different organs.
We experimentally infected siskins (Spinus spinus) with the avian malaria
parasite Plasmodium ashfordi, and used real-time quantitative polymerase chain
reaction (PCR) to measure telomere length in control and experimentally infected
siskins. We found that experimentally infected birds showed faster telomere
attrition in blood over the course of infection compared with control individuals
(repeatedly measured over 105 days post-infection (DPI)). Shorter telomeres were
also found in the tissue of all six major organs investigated (liver, lungs,
spleen, heart, kidney, and brain) in infected birds compared with controls at 105
DPI. To the best of our knowledge, this is the first study showing that an
infectious disease results in synchronous telomere shortening in the blood and
tissue cells of internal organs within individuals, implying that the infection
induces systemic stress. Our results have far-reaching implications for
understanding how the short-term effects of an infection can translate into long
term costs, such as organ dysfunction, degenerative diseases, and ageing.
PMID- 27488652
TI - Seeing red to being red: conserved genetic mechanism for red cone oil droplets
and co-option for red coloration in birds and turtles.
AB - Avian ketocarotenoid pigments occur in both the red retinal oil droplets that
contribute to colour vision and bright red coloration used in signalling. Turtles
are the only other tetrapods with red retinal oil droplets, and some also display
red carotenoid-based coloration. Recently, the CYP2J19 gene was strongly
implicated in ketocarotenoid synthesis in birds. Here, we investigate CYP2J19
evolution in relation to colour vision and red coloration in reptiles using
genomic and expression data. We show that turtles, but not crocodiles or
lepidosaurs, possess a CYP2J19 orthologue, which arose via gene duplication
before turtles and archosaurs split, and which is strongly and specifically
expressed in the ketocarotenoid-containing retina and red integument. We infer
that CYP2J19 initially functioned in colour vision in archelosaurs and conclude
that red ketocarotenoid-based coloration evolved independently in birds and
turtles via gene regulatory changes of CYP2J19 Our results suggest that red oil
droplets contributed to colour vision in dinosaurs and pterosaurs.
PMID- 27488653
TI - Lifespan, growth rate, and body size across latitude in marine Bivalvia, with
implications for Phanerozoic evolution.
AB - Mean body size in marine animals has increased more than 100-fold since the
Cambrian, a discovery that brings to attention the key life-history parameters of
lifespan and growth rate that ultimately determine size. Variation in these
parameters is not well understood on the planet today, much less in deep time.
Here, we present a new global database of maximum reported lifespan and shell
growth coupled with body size data for 1 148 populations of marine bivalves and
show that (i) lifespan increases, and growth rate decreases, with latitude, both
across the group as a whole and within well-sampled species, (ii) growth rate,
and hence metabolic rate, correlates inversely with lifespan, and (iii) opposing
trends in lifespan and growth combined with high variance obviate any
demonstrable pattern in body size with latitude. Our observations suggest that
the proposed increase in metabolic activity and demonstrated increase in body
size of organisms over the Phanerozoic should be accompanied by a concomitant
shift towards faster growth and/or shorter lifespan in marine bivalves. This
prediction, testable from the fossil record, may help to explain one of the more
fundamental patterns in the evolutionary and ecological history of animal life on
this planet.
PMID- 27488654
TI - Loss of MPZL3 function causes seborrhoeic dermatitis-like phenotype in mice.
PMID- 27488655
TI - Development and optimization of a competitive binding assay for the galactophilic
low affinity lectin LecA from Pseudomonas aeruginosa.
AB - Infections with the Gram-negative bacterium Pseudomonas aeruginosa result in a
high mortality among immunocompromised patients and those with cystic fibrosis.
The pathogen can switch from planktonic life to biofilms, and thereby shields
itself against antibiotic treatment and host immune defense to establish chronic
infections. The bacterial protein LecA, a C-type lectin, is a virulence factor
and an integral component for biofilm formation. Inhibition of LecA with its
carbohydrate ligands results in reduced biofilm mass, a potential Achilles heel
for treatment. Here, we report the development and optimization of a fluorescence
polarization-based competitive binding assay with LecA for application in
screening of potential inhibitors. As a consequence of the low affinity of d
galactose for LecA, the fluorescent ligand was optimized to reduce protein
consumption in the assay. The assay was validated using a set of known inhibitors
of LecA and IC50 values in good agreement with the known Kd values were obtained.
Finally, we employed the optimized assay to screen sets of synthetic thio
galactosides and natural blood group antigens and report their structure-activity
relationship. In addition, we evaluated a multivalent fluorescent assay probe for
LecA and report its applicability in an inhibition assay.
PMID- 27488656
TI - Effects of Newtonian gravitational self-interaction in harmonically trapped
quantum systems.
AB - The Schrodinger-Newton equation has gained attention in the recent past as a
nonlinear modification of the Schrodinger equation due to a gravitational self
interaction. Such a modification is expected from a fundamentally semi-classical
theory of gravity and can, therefore, be considered a test case for the necessity
of the quantisation of the gravitational field. Here we provide a thorough study
of the effects of the Schrodinger-Newton equation for a micron-sized sphere
trapped in a harmonic oscillator potential. We discuss both the effect on the
energy eigenstates and the dynamical behaviour of squeezed states, covering the
experimentally relevant parameter regimes.
PMID- 27488657
TI - Psychometric properties of the Postpartum Depression Predictors Inventory-Revised
for pregnant women in Mexico.
AB - This study assessed the reliability and concurrent validity of the prenatal
section of the Postpartum Depression Predictors Inventory-Revised for 250
pregnant women receiving prenatal care in Mexico. The Postpartum Depression
Predictors Inventory-Revised has shown adequate psychometric properties for
English-speaking perinatal women, but no similar data have been reported for
Spanish-speaking samples. The results show that the Postpartum Depression
Predictors Inventory-Revised is highly reliable and exhibits adequate concurrent
validity compared to the Edinburgh Postnatal Depression Scale. These findings
suggest that the Postpartum Depression Predictors Inventory-Revised can be a
reliable instrument in prenatal care services for detecting risk factors for
perinatal depression in Mexican women and potentially in other Spanish-speaking
populations.
PMID- 27488658
TI - Routine primary care screening for intimate partner violence and other adverse
psychosocial exposures: what's the evidence?
AB - BACKGROUND: Family physicians and other primary care practitioners are encouraged
or expected to screen for an expanding array of concerns and problems including
intimate partner violence (IPV). While there is no debate about the deleterious
impact of violence and other adverse psychosocial exposures on health status, the
key question raised here is about the value of routine screening in primary care
for such exposures. DISCUSSION: Several characteristics of IPV have led to
consideration for routine IPV screening in primary care and during other
healthcare encounters (e.g., emergency room visits) including: its high
prevalence, concern that it may not be raised spontaneously if not prompted, and
the burden of suffering associated with this exposure. Despite these factors,
there are now three randomized controlled trials showing that screening does not
reduce IPV or improve health outcomes. Yet, recommendations to routinely screen
for IPV persist. Similarly, adverse childhood experiences (ACEs) have several
characteristics (e.g., high frequency, predictive power of such experiences for
subsequent health problems, and concerns that they might not be identified
without screening) suggesting they too should be considered for routine primary
care screening. However, demonstration of strong associations with health
outcomes, and even causality, do not necessarily translate into the benefits of
routine screening for such experiences. To date, there have been no controlled
trials examining the impact and outcomes - either beneficial or harmful - of
routine ACEs screening. Even so, there is an expansion of calls for routine
screening for ACEs. While we must prioritize how best to support and intervene
with patients who have experienced IPV and other adverse psychosocial exposures,
we should not be lulled into a false sense of security that our routine use of
"screeners" results in better health outcomes or less violence without evidence
for such. Decisions about implementation of routine screening for psychosocial
concerns need similar rigorous debate and scrutiny of empirical evidence as that
recommended for proposed physical health screening (e.g., for prostate and breast
cancer).
PMID- 27488659
TI - Detection and identification of the heterogeneous novel subgroup 16SrXIII-(A/I)I
phytoplasma associated with strawberry green petal disease and Mexican periwinkle
virescence.
AB - Phytoplasmas (species of the genus 'CandidatusPhytoplasma') are insect-vectored
phytopathogenic bacteria associated with economically and ecologically important
crop diseases. Strawberry production represents an important part of agricultural
activity in Mexico and elsewhere, and infection of plants with phytoplasma
renders the fruit inedible by altering plant development, resulting in virescence
and phyllody. In this study we examined samples taken from four strawberry plants
showing symptoms associated with strawberry green petal disease and from two
periwinkle plants showing virescence, sampled in different areas of Mexico.
Analysis of the 16S rRNA-encoding sequences showed that the plants were infected
with a phytoplasma previously identified as Mexican periwinkle virescence (MPV;
16SrXIII). Examination of bacterial sequences from these samples revealed that
two distinct 16S rRNA gene sequences were present in each sample along with a
single chaperonin-60 (cpn60) sequence and a single rpoB sequence, suggesting that
this strain displays 16S rRNA gene sequence heterogeneity. Two distinct rrn
operons, identified with subgroup 16SrXIII-A and the newly described subgroup
16SrXIII-I, were identified from the six samples analyzed, delineating the novel
subgroup 16SrXIII-(A/I)I, following the nomenclature proposed for heterogeneous
subgroups.
PMID- 27488660
TI - Increased hypertrophic response with increased mechanical load in skeletal
muscles receiving identical activity patterns.
AB - It is often assumed that mechanical factors are important for effects of exercise
on muscle, but during voluntary training and most experimental conditions the
effects could solely be attributed to differences in electrical activity, and
direct evidence for a mechanosensory pathway has been scarce. We here show that,
in rat muscles stimulated in vivo under deep anesthesia with identical electrical
activity patterns, isometric contractions induced twofold more hypertrophy than
contractions with 50-60% of the isometric force. The number of myonuclei and the
RNA levels of myogenin and myogenic regulatory factor 4 were increased with high
load, suggesting that activation of satellite cells is mechano dependent. On the
other hand, training induced a major shift in fiber type distribution from type
2b to 2x that was load independent, indicating that the electrical signaling
rather than mechanosignaling controls fiber type. RAC-alpha serine/threonine
protein kinase (Akt) and ribosomal protein S6 kinase beta-1 (S6K1) were not
significantly differentially activated by load, suggesting that the differences
in mechanical factors were not important for activating the Akt/mammalian target
of rapamycin/S6K1 pathway. The transmembrane molecule syndecan-4 implied in
overload hypertrophy in cardiac muscle was not load dependent, suggesting that
mechanosignaling in skeletal muscle is different.
PMID- 27488661
TI - Tensional homeostasis in endothelial cells is a multicellular phenomenon.
AB - Mammalian cells of various types exhibit the remarkable ability to adapt to
externally applied mechanical stresses and strains. Because of this adaptation,
cells can maintain their endogenous mechanical tension at a preferred
(homeostatic) level, which is essential for normal physiological functions of
cells and tissues and provides protection against various diseases, including
atherosclerosis and cancer. Conventional wisdom is that the cell possesses the
ability to maintain tensional homeostasis on its own. Recent findings showed,
however, that isolated cells cannot maintain tensional homeostasis. Here we
studied the effect of multicellular interactions on tensional homeostasis by
measuring traction forces in isolated bovine aortic endothelial cells and in
confluent and nonconfluent cell clusters of different sizes. We found that, in
isolated cells, the traction field exhibited a highly dynamic and erratic
behavior. However, in cell clusters, dynamic fluctuations of the traction field
became attenuated with increasing cluster size, at a rate that was faster in
nonconfluent than confluent clusters. The driving mechanism of attenuation of
traction field fluctuations was statistical averaging of the noise, and the
impeding mechanism was nonuniform stress distribution in the clusters, which
resulted from intercellular force transmission, known as a "global tug-of-war."
These results show that isolated cells could not maintain tensional homeostasis,
which confirms previous findings, and that tensional homeostasis is a
multicellular phenomenon, which is a novel finding.
PMID- 27488662
TI - Ketoisocaproic acid, a metabolite of leucine, suppresses insulin-stimulated
glucose transport in skeletal muscle cells in a BCAT2-dependent manner.
AB - Although leucine has many positive effects on metabolism in multiple tissues,
elevated levels of this amino acid and the other branched-chain amino acids
(BCAAs) and their metabolites are implicated in obesity and insulin resistance.
While some controversies exist about the direct effect of leucine on insulin
action in skeletal muscle, little is known about the direct effect of BCAA
metabolites. Here, we first showed that the inhibitory effect of leucine on
insulin-stimulated glucose transport in L6 myotubes was dampened when other amino
acids were present, due in part to a 140% stimulation of basal glucose transport
(P < 0.05). Importantly, we also showed that alpha-ketoisocaproic acid (KIC), an
obligatory metabolite of leucine, stimulated mTORC1 signaling but suppressed
insulin-stimulated glucose transport (-34%, P < 0.05) in an mTORC1-dependent
manner. The effect of KIC on insulin-stimulated glucose transport was abrogated
in cells depleted of branched-chain aminotransferase 2 (BCAT2), the enzyme that
catalyzes the reversible transamination of KIC to leucine. We conclude that
although KIC can modulate muscle glucose metabolism, this effect is likely a
result of its transamination back to leucine. Therefore, limiting the
availability of leucine, rather than those of its metabolites, to skeletal muscle
may be more critical in the management of insulin resistance and its sequelae.
PMID- 27488663
TI - Toll-like receptor 4 mutation suppresses hyperhomocysteinemia-induced
hypertension.
AB - Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the
mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane
protein that is ubiquitously expressed in all cell types of the vasculature. TLR
4 activation has been known to promote inflammation that has been associated with
the pathogenesis of hypertension. In this study we hypothesize that HHcy induces
hypertension by TLR-4 activation, which promotes inflammatory cytokine (IL-1beta,
IL-6, and TNF-alpha) upregulation and initiation of mitochondria-dependent
apoptosis, leading to cell death and chronic vascular inflammation. To test this
hypothesis, we used C57BL/6J (WT) mice, cystathionine beta-synthase (CBS)
deficient (CBS+/-) mice with genetic mild HHcy, C3H/HeJ (C3H) mice with TLR-4
mutation, and mice with combined genetic HHcy and TLR-4 mutation (CBS+/-/C3H).
Ultrasonography of the superior mesenteric artery (SMA) detected an increase in
wall-to-lumen ratio, resistive index (RI), and pulsatility index (PI). Tail cuff
blood pressure (BP) measurement revealed elevated BP in CBS+/- mice. RI, PI, and
wall-to-lumen ratio of the SMA in CBS+/-/C3H mice were similar to the control
group, and BP was significantly alleviated. TLR-4, IL-1beta, IL-6, and TNF-alpha
expression were upregulated in the SMA of CBS+/- mice and reduced in the SMA of
CBS+/-/C3H mice. Molecules involved in the mitochondria-mediated cell death
pathway (BAX, caspase-9, and caspase-3) were upregulated in CBS+/- mice and
attenuated in CBS+/-/C3H mice. We conclude that HHcy promotes TLR-4-driven
chronic vascular inflammation and mitochondria-mediated cell death, inducing
hypertension. TLR-4 mutation attenuates vascular inflammation and cell death,
which suppress hypertension.
PMID- 27488664
TI - Activation of Nrf2 contributes to the protective effect of Exendin-4 against
angiotensin II-induced vascular smooth muscle cell senescence.
AB - Oxidative stress and impaired antioxidant defense are believed to be contributors
to the cardiovascular aging process. The transcription factor nuclear factor-E2
related factor 2 (Nrf2) plays a key role in orchestrating cellular antioxidant
defenses and maintaining redox homeostasis. Our previous study showed that
Exendin-4, a glucagon-like peptide-1 analog, alleviates angiotensin II (ANG II)
induced vascular smooth muscle cell (VSMC) senescence by inhibiting Rac1
activation via cAMP/PKA (Zhao L, Li AQ, Zhou TF, Zhang MQ, Qin XM. Am J Physiol
Cell Physiol 307: C1130-C1141, 2014). The objective of this study is to
investigate if Nrf2 mediates the antisenescent effect of Exendin-4 in ANG II
induced VSMCs. Here we report that Exendin-4 triggered Nrf2 nuclear
translocation, a downstream target of cAMP-responsive element-binding protein
(CREB) and expressions of antioxidant genes heme oxygenase-1 (HO-1) and NAD(P)H
quinone oxidoreductase-1 (NQO-1) in a dose- and time-dependent manner. In
addition, knock-down of Nrf2 attenuated the inhibitory effects of Exendin-4 on
ANG II-induced superoxidant generation and VSMC senescence. PKA/CREB pathway
participated in the upregulations of HO-1 and NQO-1 induced by Exendin-4.
Notably, our study revealed that Exendin-4 dose-dependently increased the
acetylation of Nrf2 and the recruitment of transcriptional coactivator CREB
binding protein (CBP) to Nrf2. The Exendin-4-induced Nrf2 transactivation was
diminished in the presence of CBP small interfering RNA. Microscope imaging of
Nrf2, as well as immunoblotting for Nrf2, showed that the Exendin-4-evoked Nrf2
acetylation favored its nuclear retention. Importantly, CBP silencing attenuated
the suppressing effects of Exendin-4 on ANG II-induced VSMC senescence and
superoxidant production. In conclusion, these results provide a mechanistic
insight into how Nrf2 signaling mediates the antisenescent and antioxidative
effects induced by Exendin-4 in VSMCs.
PMID- 27488666
TI - PIP2 in pancreatic beta-cells regulates voltage-gated calcium channels by a
voltage-independent pathway.
AB - Phosphatidylinositol-4,5-bisphosphate (PIP2) is a membrane phosphoinositide that
regulates the activity of many ion channels. Influx of calcium primarily through
voltage-gated calcium (CaV) channels promotes insulin secretion in pancreatic
beta-cells. However, whether CaV channels are regulated by PIP2, as is the case
for some non-insulin-secreting cells, is unknown. The purpose of this study was
to investigate whether CaV channels are regulated by PIP2 depletion in pancreatic
beta-cells through activation of a muscarinic pathway induced by oxotremorine
methiodide (Oxo-M). CaV channel currents were recorded by the patch-clamp
technique. The CaV current amplitude was reduced by activation of the muscarinic
receptor 1 (M1R) in the absence of kinetic changes. The Oxo-M-induced inhibition
exhibited the hallmarks of voltage-independent regulation and did not involve PKC
activation. A small fraction of the Oxo-M-induced CaV inhibition was diminished
by a high concentration of Ca2+ chelator, whereas >=50% of this inhibition was
prevented by diC8-PIP2 dialysis. Localization of PIP2 in the plasma membrane was
examined by transfecting INS-1 cells with PH-PLCdelta1, which revealed a close
temporal association between PIP2 hydrolysis and CaV channel inhibition.
Furthermore, the depletion of PIP2 by a voltage-sensitive phosphatase reduced CaV
currents in a way similar to that observed following M1R activation. These
results indicate that activation of the M1R pathway inhibits the CaV channel via
PIP2 depletion by a Ca2+-dependent mechanism in pancreatic beta- and INS-1 cells
and thereby support the hypothesis that membrane phospholipids regulate ion
channel activity by interacting with ion channels.
PMID- 27488665
TI - Insulin and SGK1 reduce the function of Na+/monocarboxylate transporter 1
(SMCT1/SLC5A8).
AB - SMCTs move several important fuel molecules that are involved in lipid,
carbohydrate, and amino acid metabolism, but their regulation has been poorly
studied. Insulin controls the translocation of several solutes that are involved
in energetic cellular metabolism, including glucose. We studied the effect of
insulin on the function of human SMCT1 expressed in Xenopus oocytes. The addition
of insulin reduced alpha-keto-isocaproate (KIC)-dependent 22Na+ uptake by 29%.
Consistent with this result, the coinjection of SMCT1 with SGK1 cRNA decreased
the KIC-dependent 22Na+ uptake by 34%. The reduction of SMCT1 activity by SGK1
depends on its kinase activity, and it was observed that the coinjection of SMCT1
with S442D-SGK1 (a constitutively active mutant) decreased the KIC-dependent
22Na+ uptake by 50%. In contrast, an SMCT1 coinjection with K127M-SGK1 (an
inactive mutant) had no effect on the KIC-dependent Na+ uptake. The decreasing
SMCT1 function by insulin or SGK1 was corroborated by measuring [1-14C]acetate
uptake and the electric currents of SMCT1-injected oocytes. Previously, we found
that SMCT2/Slc5a12-mRNA, but not SMCT1/Slc5a8-mRNA, is present in zebrafish
pancreas (by in situ hybridization); however, SLC5a8 gene silencing was
associated with the development of human pancreatic cancer. We confirmed that the
mRNA and protein of both transporters were present in rat pancreas using RT-PCR
with specific primers, Western blot analysis, and immunohistochemistry.
Additionally, significant propionate-dependent 22Na+ uptake occurred in
pancreatic islets and was reduced by insulin treatment. Our data indicate that
human SMCT1 is regulated by insulin and SGK1 and that both SMCTs are present in
the mammalian pancreas.
PMID- 27488667
TI - KATP channel deficiency in mouse FDB causes an impairment of energy metabolism
during fatigue.
AB - The skeletal muscle ATP-sensitive K+ (KATP) channel is crucial in preventing
fiber damage and contractile dysfunction, possibly by preventing damaging ATP
depletion. The objective of this study was to investigate changes in energy
metabolism during fatigue in wild-type and inwardly rectifying K+ channel
(Kir6.2)-deficient (Kir6.2-/-) flexor digitorum brevis (FDB), a muscle that lacks
functional KATP channels. Fatigue was elicited with one tetanic contraction every
second. Decreases in ATP and total adenylate levels were significantly greater in
wild-type than Kir6.2-/- FDB during the last 2 min of the fatigue period.
Glycogen depletion was greater in Kir6.2-/- FDB for the first 60 s, but not by
the end of the fatigue period, while there was no difference in glucose uptake.
The total amount of glucosyl units entering glycolysis was the same in wild-type
and Kir6.2-/- FDB. During the first 60 s, Kir6.2-/- FDB generated less lactate
and more CO2; in the last 120 s, Kir6.2-/- FDB stopped generating CO2 and
produced more lactate. The ATP generated during fatigue from phosphocreatine,
glycolysis (lactate), and oxidative phosphorylation (CO2) was 3.3-fold greater in
Kir6.2-/- than wild-type FDB. Because ATP and total adenylate were significantly
less in Kir6.2-/- FDB, it is suggested that Kir6.2-/- FDB has a greater energy
deficit, despite a greater ATP production, which is further supported by greater
glucose uptake and lactate and CO2 production in Kir6.2-/- FDB during the
recovery period. It is thus concluded that a lack of functional KATP channels
results in an impairment of energy metabolism.
PMID- 27488668
TI - Activation of MEK/ERK signaling contributes to the PACAP-induced increase in
guinea pig cardiac neuron excitability.
AB - Pituitary adenylate cyclase (PAC)-activating polypeptide (PACAP) peptides
(Adcyap1) signaling at the selective PAC1 receptor (Adcyap1r1) participate in
multiple homeostatic and stress-related responses, yet the cellular mechanisms
underlying PACAP actions remain to be completely elucidated. PACAP/PAC1 receptor
signaling increases excitability of neurons within the guinea pig cardiac
ganglia, and as these neurons are readily accessible, this neuronal system is
particularly amenable to study of PACAP modulation of ionic conductances. The
present study investigated how PACAP activation of MEK/ERK signaling contributed
to the peptide-induced increase in cardiac neuron excitability. Treatment with
the MEK inhibitor PD 98059 blocked PACAP-stimulated phosphorylated ERK and, in
parallel, suppressed the increase in cardiac neuron excitability. However, PD
98059 did not blunt the ability of PACAP to enhance two inward ionic currents,
one flowing through hyperpolarization-activated nonselective cationic channels
(Ih) and another flowing through low-voltage-activated calcium channels (IT),
which support the peptide-induced increase in excitability. Thus a PACAP- and
MEK/ERK-sensitive, voltage-dependent conductance(s), in addition to Ih and IT,
modulates neuronal excitability. Despite prior work implicating PACAP
downregulation of the KV4.2 potassium channel in modulation of excitability in
other cells, treatment with the KV4.2 current blocker 4-aminopyridine did not
replicate the PACAP-induced increase in excitability in cardiac neurons. However,
cardiac neurons express the ERK target, the NaV1.7 sodium channel, and treatment
with the selective NaV1.7 channel inhibitor PF-04856264 decreased the PACAP
modulation of excitability. From these results, PACAP/PAC1 activation of MEK/ERK
signaling may phosphorylate the NaV1.7 channel, enhancing sodium currents near
the threshold, an action contributing to repetitive firing of the cardiac neurons
exposed to PACAP.
PMID- 27488669
TI - Nuclear V-type ATPase. Focus on "Vacuolar H+-ATPase in the nuclear membranes
regulates nucleo-cytosolic proton gradients".
PMID- 27488670
TI - New pieces in the complex puzzle of aberrant vacuolation. Focus on "Active
vacuolar H+ ATPase and functional cycle of Rab5 are required for the vacuolation
defect triggered by PtdIns(3,5)P2 loss under PIKfyve or Vps34 deficiency".
PMID- 27488672
TI - The potassium channels TASK2 and TREK1 regulate functional differentiation of
murine skeletal muscle cells.
AB - Two-pore domain potassium (K2P) channels influence basic cellular parameters such
as resting membrane potential, cellular excitability, or intracellular Ca2+
concentration [Ca2+]i While the physiological importance of K2P channels in
different organ systems (e.g., heart, central nervous system, or immune system)
has become increasingly clear over the last decade, their expression profile and
functional role in skeletal muscle cells (SkMC) remain largely unknown. The mouse
SkMC cell line C2C12, wild-type mouse muscle tissue, and primary mouse muscle
cells (PMMs) were analyzed using quantitative PCR, Western blotting, and
immunohistochemical stainings as well as functional analysis including patch
clamp measurements and Ca2+ imaging. Mouse SkMC express TWIK-related acid
sensitive K+ channel (TASK) 2, TWIK-related K+ channel (TREK) 1, TREK2, and TWIK
related arachidonic acid stimulated K+ channel (TRAAK). Except TASK2 all
mentioned channels were upregulated in vitro during differentiation from
myoblasts to myotubes. TASK2 and TREK1 were also functionally expressed and
upregulated in PMMs isolated from mouse muscle tissue. Inhibition of TASK2 and
TREK1 during differentiation revealed a morphological impairment of myoblast
fusion accompanied by a downregulation of maturation markers. TASK2 and TREK1
blockade led to a decreased K+ outward current and a decrease of ACh-dependent
Ca2+ influx in C2C12 cells as potential underlying mechanisms. K2P-channel
expression was also detected in human muscle tissue by immunohistochemistry
pointing towards possible relevance for human muscle cell maturation and
function. In conclusion, our findings for the first time demonstrate the
functional expression of TASK2 and TREK1 in muscle cells with implications for
differentiation processes warranting further investigations in physiologic and
pathophysiologic scenarios.
PMID- 27488673
TI - Our self-tracking movement and health literacy: are we really making every moment
count?
AB - There is a growing movement related to self-tracking in the quest for better
health. Why do so many people like to use 'intelligent tools' like shiny sensors
or mobile apps to keep an eye on every move? Do they really help us drive
sustained healthy behavioral changes? Despite technological advances and product
promises, we must remember that technology alone does not facilitate change to
optimize health benefits. The purpose of the commentary is to pose the question:
How 'health literate' do we have to be to reap the actionable health benefits of
self-tracking? Research has revealed the prevalence of limited health literacy
across the globe. Health literacy involves a complex set of inter-connected
skills, including acting upon health information. This commentary puts attention
on health literacy as an essential human tool to better equip people to overcome
barriers and use devices to leverage their full potential.
PMID- 27488671
TI - Deletion of calponin 2 in macrophages attenuates the severity of inflammatory
arthritis in mice.
AB - Calponin is an actin cytoskeleton-associated protein that regulates motility
based cellular functions. Three isoforms of calponin are present in vertebrates,
among which calponin 2 encoded by the Cnn2 gene is expressed in multiple types of
cells, including blood cells from the myeloid lineage. Our previous studies
demonstrated that macrophages from Cnn2 knockout (KO) mice exhibit increased
migration and phagocytosis. Intrigued by an observation that monocytes and
macrophages from patients with rheumatoid arthritis had increased calponin 2, we
investigated anti-glucose-6-phosphate isomerase serum-induced arthritis in Cnn2
KO mice for the effect of calponin 2 deletion on the pathogenesis and pathology
of inflammatory arthritis. The results showed that the development of arthritis
was attenuated in systemic Cnn2-KO mice with significantly reduced inflammation
and bone erosion than that in age- and stain background-matched C57BL/6 wild-type
mice. In vitro differentiation of calponin 2-null mouse bone marrow cells
produced fewer osteoclasts with decreased bone resorption. The attenuation of
inflammatory arthritis was confirmed in conditional myeloid cell-specific Cnn2-KO
mice. The increased phagocytotic activity of calponin 2-null macrophages may
facilitate the clearance of autoimmune complexes and the resolution of
inflammation, whereas the decreased substrate adhesion may reduce
osteoclastogenesis and bone resorption. The data suggest that calponin 2
regulation of cytoskeleton function plays a novel role in the pathogenesis of
inflammatory arthritis, implicating a potentially therapeutic target.
PMID- 27488674
TI - Why is malaria associated with poverty? Findings from a cohort study in rural
Uganda.
AB - BACKGROUND: Malaria control and sustainable development are linked, but
implementation of 'multisectoral' intervention is restricted by a limited
understanding of the causal pathways between poverty and malaria. We investigated
the relationships between socioeconomic position (SEP), potential determinants of
SEP, and malaria in Nagongera, rural Uganda. METHODS: Socioeconomic information
was collected for 318 children aged six months to 10 years living in 100
households, who were followed for up to 36 months. Mosquito density was recorded
using monthly light trap collections. Parasite prevalence was measured routinely
every three months and malaria incidence determined by passive case detection.
First, we evaluated the association between success in smallholder agriculture
(the primary livelihood source) and SEP. Second, we explored socioeconomic risk
factors for human biting rate (HBR), parasite prevalence and incidence of
clinical malaria, and spatial clustering of socioeconomic variables. Third, we
investigated the role of selected factors in mediating the association between
SEP and malaria. RESULTS: Relative agricultural success was associated with
higher SEP. In turn, high SEP was associated with lower HBR (highest versus
lowest wealth index tertile: Incidence Rate Ratio 0.71, 95 % confidence intervals
(CI) 0.54-0.93, P = 0.01) and lower odds of malaria infection in children
(highest versus lowest wealth index tertile: adjusted Odds Ratio 0.52, 95 % CI
0.35-0.78, P = 0.001), but SEP was not associated with clinical malaria
incidence. Mediation analysis suggested that part of the total effect of SEP on
malaria infection risk was explained by house type (24.9 %, 95 % CI 15.8-58.6 %)
and food security (18.6 %, 95 % CI 11.6-48.3 %); however, the assumptions of the
mediation analysis may not have been fully met. CONCLUSION: Housing improvements
and agricultural development interventions to reduce poverty merit further
investigation as multisectoral interventions against malaria. Further
interdisplinary research is needed to understand fully the complex pathways
between poverty and malaria and to develop strategies for sustainable malaria
control.
PMID- 27488675
TI - Cost-effectiveness analysis of bortezomib in combination with rituximab,
cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP) in patients
with previously untreated mantle cell lymphoma.
AB - BACKGROUND: Mantle cell lymphoma (MCL) is a rare and aggressive form of non
Hodgkin's lymphoma. Bortezomib is the first product to be approved for the
treatment of patients with previously untreated MCL, for whom haematopoietic stem
cell transplantation is unsuitable, and is used in combination with rituximab,
cyclophosphamide, doxorubicin, vincristine and prednisone (VR-CAP). The National
Institute of Health and Care Excellence recently recommended the use of VR-CAP in
the UK following a technology appraisal. We present the cost effectiveness
analysis performed as part of that assessment: VR-CAP versus the current standard
of care regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and
prednisone (R-CHOP) in a UK setting. METHODS: A lifetime economic model was
developed with health states based upon line of treatment and progression status.
Baseline patient characteristics, dosing, safety and efficacy were based on the
LYM-3002 trial. As overall survival data were immature, survival was modelled by
progression status, and post-progression survival was assumed equal across arms.
Utilities were derived from LYM-3002 and literature, and standard UK cost sources
were used. RESULTS: Treatment with VR-CAP compared to R-CHOP gave an incremental
quality-adjusted life year (QALY) gain of 0.81 at an additional cost of L16,212,
resulting in a base case incremental cost-effectiveness ratio of L20,043.
Deterministic and probabilistic sensitivity analyses showed that treatment with
VR-CAP was cost effective at conventional willingness-to-pay thresholds (L20,000
L30,000 per QALY). CONCLUSIONS: VR-CAP is a cost-effective option for previously
untreated patients with MCL in the UK.
PMID- 27488676
TI - Erratum to: B-cell repertoire dynamics after sequential hepatitis B vaccination
and evidence for cross-reactive B-cell activation.
PMID- 27488677
TI - Corrigendum: Cidea improves the metabolic profile through expansion of adipose
tissue.
PMID- 27488678
TI - Iron Telluride-Decorated Reduced Graphene Oxide Hybrid Microspheres as Anode
Materials with Improved Na-Ion Storage Properties.
AB - Transition-metal telluride materials are studied as the anode materials for Na
ion batteries (NIBs). The FeTe2-reduced graphene oxide (rGO) hybrid powders
(first target material) are prepared via spray pyrolysis and subsequent
tellurization. The H2Te gas treatment transforms the Fe3O4-rGO powders to FeTe2
rGO hybrid powders with FeTe2 nanocrystals (various sizes <100 nm) embedded
within the rGO. The FeTe2-rGO hybrid powders contain 5 wt % rGO. The Na-ion
storage mechanism for FeTe2 in NIBs is described by FeTe2 + 4Na(+) + 4e(-)<->Fe +
2Na2Te. The FeTe2-rGO hybrid discharge process forms metallic Fe nanocrystals and
Na2Te by a conversion reaction of FeTe2 with Na ions. The discharge capacities of
the FeTe2-rGO hybrid powders for the first and 80th cycles are 493 and 293 mA h
g(-1), respectively. The discharge capacities of the bare FeTe2 powders for the
first and 80th cycles are 462 and 83 mA h g(-1), respectively. The FeTe2-rGO
hybrid powders have superior Na-ion storage properties compared to bare FeTe2
powders owing to their high structural stability and electrical conductivity.
PMID- 27488679
TI - Nanodiamonds: a critical component of anodes for high performance lithium-ion
batteries.
AB - Detonation nanodiamonds (DNDs) have been introduced into a carbonaceous anode for
improving the performance of lithium ion batteries (LIBs). The lithium storage
capacity, cycling performance and stability of the LIBs are increased and this is
related to the DNDs' unique characteristics of chemical inertness, a larger
surface area, low expansion, and high lithium adsorption capacity.
PMID- 27488680
TI - Advances in drug delivery to high grade gliomas.
AB - If cancer is hard to be treated, brain cancer is even more, caused by the
inability of many effective drugs given systemically to cross the blood brain and
blood tumor barriers and reach adequate concentrations at the tumor sites.
Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit
not sufficient, condition to effectively target the disease. In order to analyze
the current status of research on drug delivery to high grade gliomas (HGG-WHO
grades III and IV), the most frequent and aggressive brain cancers, a literature
search was conducted in PubMed using the terms: "drug delivery and brain tumor"
over the publication year 2015. Currently explored drug delivery techniques for
HGG include the convection and permeabilization-enhanced deliveries, drug
releasing depots and Ommaya reservoirs. The efficacy/safety ratio widely varies
among these techniques and the success of current efforts to increase this ratio
widely varies as well.
PMID- 27488682
TI - Another example of enzymatic promiscuity: the polyphosphate kinase of
Streptomyces lividans is endowed with phospholipase D activity.
AB - Polyphosphate kinases (PPK) from different bacteria, including that of
Streptomyces lividans, were shown to contain the typical HKD motif present in
phospholipase D (PLD) and showed structural similarities to the latter. This
observation prompted us to investigate the PLD activity of PPK of S. lividans, in
vitro. The ability of PPK to catalyze the hydrolysis of phosphatidylcholine (PC),
the PLD substrate, was assessed by the quantification of [3H]phosphatidic acid
(PA) released from [3H]PC-labeled ELT3 cell membranes. Basal cell membrane PLD
activity as well as GTPgammaS-activated PLD activity was higher in the presence
than in absence of PPK. After abolition of the basal PLD activity of the
membranes by heat or tryptic treatment, the addition of PPK to cell membranes was
still accompanied by an increased production of PA demonstrating that PPK also
bears a PLD activity. PLD activity of PPK was also assessed by the production of
choline from hydrolysis of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) in the
presence of the Amplex Red reagent and compared to two commercial PLD enzymes.
These data demonstrated that PPK is endowed with a weak but clearly detectable
PLD activity. The question of the biological signification, if any, of this
enzymatic promiscuity is discussed.
PMID- 27488681
TI - Standardized measures of lobular involution and subsequent breast cancer risk
among women with benign breast disease: a nested case-control study.
AB - Lesser degrees of terminal duct-lobular unit (TDLU) involution predict higher
breast cancer risk; however, standardized measures to quantitate levels of TDLU
involution have only recently been developed. We assessed whether three
standardized measures of TDLU involution, with high intra/inter pathologist
reproducibility in normal breast tissue, predict subsequent breast cancer risk
among women in the Mayo benign breast disease (BBD) cohort. We performed a masked
evaluation of biopsies from 99 women with BBD who subsequently developed breast
cancer (cases) after a median of 16.9 years and 145 age-matched controls. We
assessed three metrics inversely related to TDLU involution: TDLU count/mm(2),
median TDLU span (microns, which approximates acini content), and median category
of acini counts/TDLU (0-10; 11-20; 21-30; 31-50; >50). Associations with
subsequent breast cancer risk for quartiles (or categories of acini counts) of
each of these measures were assessed with multivariable conditional logistic
regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI). In
multivariable models, women in the highest quartile compared to the lowest
quartiles of TDLU counts and TDLU span measures were significantly associated
with subsequent breast cancer diagnoses; TDLU counts quartile4 versus quartile1,
OR = 2.44, 95 %CI 0.96-6.19, p-trend = 0.02; and TDLU spans, quartile4 versus
quartile1, OR = 2.83, 95 %CI = 1.13-7.06, p-trend = 0.03. Significant
associations with categorical measures of acini counts/TDLU were also observed:
compared to women with median category of <10 acini/TDLU, women with >25 acini
counts/TDLU were at significantly higher risk, OR = 3.40, 95 %CI 1.03-11.17, p
trend = 0.032. Women with TDLU spans and TDLU count measures above the median
were at further increased risk, OR = 3.75 (95 %CI 1.40-10.00, p-trend = 0.008),
compared with women below the median for both of these metrics. Similar results
were observed for combinatorial metrics of TDLU acini counts/TDLU, and TDLU
count. Standardized quantitative measures of TDLU counts and acini counts
approximated by TDLU span measures or visually assessed in categories are
independently associated with breast cancer risk. Visual assessment of TDLU
numbers and acini content, which are highly reproducible between pathologists,
could help identify women at high risk for subsequent breast cancer among the
million women diagnosed annually with BBD in the US.
PMID- 27488683
TI - Tutorial in biostatistics: data-driven subgroup identification and analysis in
clinical trials.
AB - It is well known that both the direction and magnitude of the treatment effect in
clinical trials are often affected by baseline patient characteristics (generally
referred to as biomarkers). Characterization of treatment effect heterogeneity
plays a central role in the field of personalized medicine and facilitates the
development of tailored therapies. This tutorial focuses on a general class of
problems arising in data-driven subgroup analysis, namely, identification of
biomarkers with strong predictive properties and patient subgroups with desirable
characteristics such as improved benefit and/or safety. Limitations of ad-hoc
approaches to biomarker exploration and subgroup identification in clinical
trials are discussed, and the ad-hoc approaches are contrasted with principled
approaches to exploratory subgroup analysis based on recent advances in machine
learning and data mining. A general framework for evaluating predictive
biomarkers and identification of associated subgroups is introduced. The tutorial
provides a review of a broad class of statistical methods used in subgroup
discovery, including global outcome modeling methods, global treatment effect
modeling methods, optimal treatment regimes, and local modeling methods. Commonly
used subgroup identification methods are illustrated using two case studies based
on clinical trials with binary and survival endpoints. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27488684
TI - Targeting deficient DNA damage repair in gastric cancer.
AB - INTRODUCTION: Over recent years our understanding of DNA damage repair has
evolved leading to an expansion of therapies attempting to exploit DNA damage
repair deficiencies across multiple solid tumours. Gastric cancer has been
identified as a tumour where a subgroup of patients demonstrates deficiencies in
the homologous recombination pathway providing a potential novel treatment
approach for this poor prognosis disease. AREA COVERED: This review provides an
overview of DNA damage repair and how this has been targeted to date in other
tumour types exploiting the concept of synthetic lethality. This is followed by a
discussion of how deficiencies in homologous recombination may be identified
across tumour types and on recent progress in targeting DNA repair deficiencies
in gastric cancer. EXPERT OPINION: Gastric cancer remains a difficult malignancy
to treat and the possibility of targeting deficient DNA repair in a subgroup of
patients is an exciting prospect. Future combinations with immunotherapy and
radiotherapy are appealing and appear to have a sound biological rationale.
However, much work remains to be done to understand the significance of the
genetic and epigenetic alterations involved, to elucidate the optimum predictive
signatures or biomarkers and to consider means of overcoming treatment
resistance.
PMID- 27488685
TI - Modulation of nociceptive threshold by combined hormonal contraceptives in women
with oestrogen-withdrawal migraine attacks: a pilot study.
AB - BACKGROUND: Menstrually-related headache and headaches associated with oestrogen
withdrawal are common conditions, whose pathophysiology has not been completely
elucidated. In this study we evaluated the influence of combined hormonal
contraceptives (CHC) on pain threshold in women presenting migraine attacks
during hormone-free interval. FINDINGS: Eleven women with migraine attacks
recurring exclusively during the oestrogen-withdrawal period were studied with
the nociceptive flexion reflex, a neurophysiological assessment of the pain
control systems, during the third week of active treatment and during the hormone
free interval. During the hormone-free interval, nociceptive withdrawal reflex
threshold was significantly lower (12.8 +/- 8.0 mA) as compared to the third week
of hormonal treatment (15.6 +/- 6.6 mA) (p = 0.02). No change was observed in the
pain perceived and in the temporal summation. CONCLUSIONS: Oestrogen withdrawal
may mediate an increased sensitivity to somatosensory stimuli in women with
migraine attacks recurring during the hormone-free interval.
PMID- 27488686
TI - Synthesis of Dipyridyl Ketone Isonicotinoyl Hydrazone Copper(II) Complex:
Structure, Anticancer Activity and Anticancer Mechanism.
AB - In an effort to better understand the biological efficacy of the tridentate aroyl
hydrazone Cu(II) complexes, the Cu(II) complex of di-2-pyridyl ketone
isonicotinoyl hydrazone ligand (HL), {[Cu(L)(H2O)].H2O.NO3}n (C1) was synthesized
and characterized. Single crystal X-ray study reveals that complex C1 forms 1D
zigzag chains in solid state. In water, the hydrolysis of the 1D zigzag chains
was observed, and finally formation of monomeric species. In vitro studies
revealed that complex C1 showed significantly more anticancer activity than the
ligand alone. Investigation of the anticancer mechanisms of C1, confirmed that
the Cu(II) complex exhibit a strong capacity to promote productions of reactive
oxygen species (ROS), leading to caspase-dependent apoptotic cell death.
PMID- 27488687
TI - A Highly Selective and Sensitive Fluorescent Chemosensor for Aluminum Ions Based
on Schiff Base.
AB - An efficient "off-on" type fluorescent chemosensor, (E)-N'-(4-(diethylamino)-2
hydroxybenzylidene)-2-hydroxybenzohydrazide (H 2 L), based on Schiff base for the
determination of Al3+ has been designed, synthesized, and evaluated. Upon treated
with Al3+, the fluorescence of H 2 L was enhanced 45-fold due to the chelation
enhanced fluorescence (CHEF) effect based on the formation of a 1:1 complex
between the chemosensor and Al3+. Other metal ions, such as Na+, K+, Mg2+, Ca2+,
Cu2+, Ga3+, Zn2+, Cr3+, Cd2+, Ag+, Fe3+, In3+, Mn2+, Pb2+, Co2+, and Ni2+ had
little effect on the fluorescence. The results demonstrate that the chemosensor H
2 L has stronger affinity with Al3+ than other metal ions. The detection limit of
H 2 L for sensing Al3+ is 3.60 * 10-6 M in EtOH-H2O (3:7, v/v) solution. And the
recognizing behavior has been investigated both experimentally and
computationally.
PMID- 27488688
TI - The role of community pharmacists in supporting self-management in patients with
psoriasis.
AB - BACKGROUND: The majority of patients with psoriasis have mild to moderate disease
which can be managed in primary care with topical therapies. The supportive role
of pharmacists for patients with long-term dermatological conditions is largely
unknown. OBJECTIVE: To assess the impact of an educational intervention delivered
by community pharmacists to improve self-management for people with psoriasis.
METHOD: The study involved a pre- and post-intervention design. Seven community
pharmacies were selected based on their location (urban, rural etc.) and the
pharmacists recruited via local comprehensive research networks. Patients with
mild to moderate psoriasis were recruited either opportunistically or via a
letter of invite by pharmacists who undertook a face-to-face consultation with
one follow-up visit after 6 weeks. The primary outcome was the change in person
centred dermatology self-care index (PEDESI) score and secondary outcomes were
the self-assessed psoriasis and severity index (SAPASI), measuring disease
severity and the dermatology quality of life index (DLQI). KEY FINDINGS: A total
of 47 patients were recruited. At 6 weeks, 42/47 (89.3%) patients completed the
follow-up consultation. There was a significant increase in mean PEDESI scores
(25.15 versus 17.78, P < 0.001) at 6 weeks compared to baseline. Similarly,
SAPASI (11.60 versus 7.74, P < 0.001) and DLQI (7.21 versus 4.14, P < 0.001)
scores improved significantly. CONCLUSION: Pharmacist-assisted support for
patients with psoriasis improved knowledge, reduced disease severity and the
impact on quality of life. These results suggest that community pharmacists might
have an important role to play in facilitating self-management for patients with
psoriasis.
PMID- 27488689
TI - ERRATUM.
PMID- 27488691
TI - Financial Insecurity: Putting our Money where our Mouth is.
PMID- 27488693
TI - Population genetic inferences using immune gene SNPs mirror patterns inferred by
microsatellites.
AB - Single nucleotide polymorphisms (SNPs) are replacing microsatellites for
population genetic analyses, but it is not apparent how many SNPs are needed or
how well SNPs correlate with microsatellites. We used data from the gopher
tortoise, Gopherus polyphemus-a species with small populations, to compare SNPs
and microsatellites to estimate population genetic parameters. Specifically, we
compared one SNP data set (16 tortoises from four populations sequenced at 17 901
SNPs) to two microsatellite data sets, a full data set of 101 tortoises and a
partial data set of 16 tortoises previously genotyped at 10 microsatellites. For
the full microsatellite data set, observed heterozygosity, expected
heterozygosity and FST were correlated between SNPs and microsatellites; however,
allelic richness was not. The same was true for the partial microsatellite data
set, except that allelic richness, but not observed heterozygosity, was
correlated. The number of clusters estimated by structure differed for each data
set (SNPs = 2; partial microsatellite = 3; full microsatellite = 4). Principle
component analyses (PCA) showed four clusters for all data sets. More than 800
SNPs were needed to correlate with allelic richness, observed heterozygosity and
expected heterozygosity, but only 100 were needed for FST . The number of SNPs
typically obtained from next-generation sequencing (NGS) far exceeds the number
needed to correlate with microsatellite parameter estimates. Our study
illustrates that diversity, FST and PCA results from microsatellites can mirror
those obtained with SNPs. These results may be generally applicable to small
populations, a defining feature of endangered and threatened species, because
theory predicts that genetic drift will tend to outweigh selection in small
populations.
PMID- 27488692
TI - Effectiveness of educational outreach in infectious diseases management: a
cluster randomized trial in Uganda.
AB - BACKGROUND: Integrated Infectious Diseases Capacity Building Evaluation (IDCAP)
teams designed and implemented two health worker in-service training approaches:
1) an off-site classroom-based integrated management of infectious diseases
(IMID) course with distance learning aspects, and 2) on-site support (OSS), an
educational outreach intervention. We tested the effects of OSS on workload and
12 facility performance indicators for emergency triage assessment and treatment,
HIV testing, and malaria and pneumonia case management among outpatients by two
subgroups: 1) mid-level practitioners (MLP) who attended IMID training (IMID-MLP)
and 2) health workers who did not (No-IMID). METHODS: Thirty-six health
facilities participated in the IDCAP trial, with 18 randomly assigned to Arm A
and 18 to Arm B. Two MLP in both arms received IMID. All providers at Arm A
facilities received nine monthly OSS visits from April to December 2010 while Arm
B did not. From November 2009 to December 2010, 777,667 outpatient visits
occurred. We analyzed 669,580 (86.1 %) outpatient visits, where provider cadre
was reported. Treatment was provided by 64 IMID-MLP and 1,515 No-IMID providers.
The effect of OSS was measured by the difference in pre/post changes across arms
after controlling for covariates (adjusted ratio of relative risks = a RRR).
RESULTS: The effect of OSS on patients-per-provider-per-day (workload) among IMID
MLP (aRRR = 1.21; p = 0.48) and No-IMID (aRRR = 0.90; p = 0.44) was not
statistically significant. Among IMID-MLP, OSS was effective for three
indicators: malaria cases receiving an appropriate antimalarial (aRRR = 1.26, 99
% CI = 1.02-1.56), patients with negative malaria test result prescribed an
antimalarial (aRRR = 0.49, 99 % CI = 0.26-0.92), and patients with acid-fast
bacilli smear negative result receiving empiric treatment for acute respiratory
infection (aRRR = 2.04, 99 % CI = 1.06-3.94). Among No-IMID, OSS was effective
for two indicators: emergency and priority patients admitted, detained or
referred (aRRR = 2.12, 99 % CI = 1.05-4.28) and emergency patients receiving at
least one appropriate treatment (aRRR = 1.98, 99 % CI = 1.21-3.24). CONCLUSION:
Effects of OSS on workload were not statistically significant. Significant OSS
effects on facility performance across subgroups were heterogeneous. OSS
supported MLP who diagnosed and treated patients to apply IMID knowledge. For
other providers, OSS supported team work to manage emergency patients. This
evidence on OSS effectiveness could inform interventions to improve health
workers' capacity to deliver better quality infectious diseases care.
PMID- 27488694
TI - Zinc supplementation during in vitro maturation increases the production
efficiency of cloned pigs.
AB - Zinc supplementation (0.8 ug/ml) in in vitro maturation (IVM) medium
significantly enhances oocyte quality. In this study, we compared the development
of somatic cell nuclear transfer (SCNT) embryos produced from conventional IVM
(control) and zinc-supplemented IVM oocytes. A total of 1206 and 890 SCNT embryos
were produced using control and zinc-supplemented oocytes, respectively, and then
were transferred to 11 and 8 recipients, respectively. Five control recipients
and three zinc-supplemented recipients became pregnant. Two live piglets and
eight mummies were born from two control recipients, and ten live piglets and six
stillborn piglets were born from three zinc-supplemented recipients. The
production efficiency significantly increased in the zinc-supplemented group
(0.33% vs. 3.02%). This report suggests that zinc supplementation in IVM medium
improved the production efficiency of cloned pigs.
PMID- 27488695
TI - Association between time to progression and subsequent survival inceritinib
treated patients with advanced ALK-positive non-small-cell lung cancer.
AB - OBJECTIVE: Time to progression (TTP) is a surrogate marker of overall survival
(OS). However, OS is also dependent on post-progression survival (PPS). This
study evaluated the association between TTP and the duration of PPS among adult
patients who received ceritinib (Zykadia 1 ) for the treatment of advanced
anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC).
RESEARCH DESIGN AND METHODS: A pooled analysis was performed on 181 ASCEND-1
(phase I) and ASCEND-2 (phase II) patients who experienced disease progression
while on ceritinib. TTP was assessed on its association with PPS in a Kaplan
Meier analysis and in Cox proportional hazard models, adjusted for clinical
covariates. MAIN OUTCOME MEASURES: Main outcomes measured include TTP, PPS, and
OS. RESULTS: Patients with TTP >=6 months experienced significantly longer PPS
compared to those with TTP <6 months (median: 9.8 vs. 6.5 months, log-rank p
value < .01). When TTP was assessed as a continuous variable, every 3 months of
longer TTP was associated with a 21% lower hazard of death following progression
(hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.63-1.00; adjusted HR:
0.79, 95% CI: 0.64-0.99). This positive association translated into an OS
benefit: each 3 months of longer TTP was associated with a lower hazard of death
(adjusted HR: 0.46, 95% CI: 0.37-0.58). Median OS was 20.0 months for patients
with TTP >=6 months and was 10.9 months for patients with TTP <6 months.
CONCLUSIONS: A longer duration of TTP after treatment with ceritinib was
significantly associated with a longer duration of both PPS and OS.
PMID- 27488697
TI - Caesarean section and its impact on fertility and time to a subsequent pregnancy
in Germany: a database analysis in gynecological practices.
AB - PURPOSE: To analyze the impact of caesarean section (CS) on fertility and time to
pregnancy in German gynecological practices. METHODS: Women initially diagnosed
for the first time with a vaginal delivery (VD) or CS between 2000 and 2013 were
identified by 227 gynecologists in the IMS Disease Analyzer database. They were
included if they were aged between 16 and 40 years, and were not previously
diagnosed with female sterility. The two main outcomes were the first-time
diagnosis of female sterility and the time between the first delivery and the
next pregnancy within 10 years. A multivariate Cox regression model was used to
predict these outcomes on the basis of patient characteristics. RESULTS: 6483
patients were included in the CS group and 6483 in the VD group. Mean age was
30.6 years and the proportion of individuals with private health insurance
amounted to 9.0 %. Within 10 years of the index date, 19.5 % of women who
delivered by CS and 18.3 % of women who delivered vaginally were diagnosed with
sterility (p value = 0.0148). CS and polycystic ovary syndrome significantly
increased the risk of sterility. Within 10 years of the index date, 57.9 % of
women who underwent a CS and 64.0 % of women who delivered vaginally were
pregnant for the second time (p value <0.001). CS, polycystic ovary syndrome, and
the deterioration of menstrual cycle significantly decreased the chance of
becoming pregnant a second time. CONCLUSIONS: CS is associated with an increased
risk of sterility and a decreased number of subsequent pregnancies in Germany.
PMID- 27488698
TI - Growth hormone co-treatment within a GnRH agonist long protocol improves
implantation and pregnancy rates in patients undergoing IVF-ET.
AB - OBJECTIVE: The efficacy of growth hormone (GH) co-treatment within a GnRH agonist
long regimen, in women with a normal ovarian response to controlled ovarian
hyperstimulation (COH), for IVF was assessed. METHODS: This retrospective
clinical trial was performed in a private-assisted reproduction centre. The study
involved 1114 patients who responded normally to high-dose gonadotropin
treatment. The study group of 556 patients was given in a daily subcutaneous
injection of 4.5 IU of GH co-treatment, starting from the initial day of
gonadotropin treatment and lasting for 5 days. The control group of 558 patients
received the same treatment protocol without the GH co-treatment. The
participants were further divided into two subgroups: age >=35 years and age <35
years. The primary endpoint of the study was IVF-ET outcomes. RESULTS: The
demographic characteristics did not significantly differ between the groups. The
implantation rate (36.7 vs. 20.4 %, P < 0.05) and clinical pregnancy rate (57.3
vs. 30.1 %, P < 0.05) were significantly higher in the study group than in the
control group. An analysis using a multivariate logistic regression model showed
that GH was a significant factor for predicting pregnancy outcomes (OR 3.125, 95
% CI 2.441-4.000). Furthermore, for the >=35-year-old group, the endometrial
thickness was significantly greater (11.99 +/- 2.21 vs. 11.62 +/- 2.45, P < 0.05)
in the study group than in the control group; in contrast, for the <35-year-old
group, the high-quality embryo rate was significantly higher (71.7 vs. 68.3 %, P
< 0.05) in the study group than in the control group. CONCLUSION: Our study
showed that co-treatment with GH in a GnRH agonist long protocol in patients who
responded normally while undergoing IVF-ET could increase the implantation and
pregnancy rates.
PMID- 27488696
TI - Systematic review and meta-analysis of nasal potential difference in hypoxia
induced lung injury.
AB - Nasal potential difference (NPD), a well-established in vivo clinical test for
cystic fibrosis, reflects transepithelial cation and anion transport in the
respiratory epithelium. To analyze whether NPD can be applied to diagnose hypoxic
lung injury, we searched PubMed, EMBASE, Scopus, Web of Science, Ovid MEDLINE,
and Google Scholar, and analyzed data retrieved from eleven unbiased studies for
high altitude pulmonary edema (HAPE) and respiratory distress syndrome (RDS)
using the software RevMan and R. There was a significant reduction in overall
basal (WMD -5.27 mV, 95% CI: -6.03 to -4.52, P < 0.00001, I(2) = 42%), amiloride
sensitive (ENaC) (-2.87 mV, 95% CI: -4.02 to -1.72, P < 0.00001, I(2) = 51%), and
-resistant fractions (-3.91 mV, 95% CI: -7.64 to -0.18, P = 0.04, I(2) = 95%) in
lung injury patients. Further analysis of HAPE and RDS separately corroborated
these observations. Moreover, SpO2 correlated with ENaC-associated NPD positively
in patients only, but apparently related to CFTR-contributed NPD level inversely.
These correlations were confirmed by the opposite associations between NPD values
and altitude, which had a negative regression with SpO2 level. Basal NPD was
significantly associated with amiloride-resistant but not ENaC fraction. Our
analyses demonstrate that acute lung injury associated with systemic hypoxia is
characterized by dysfunctional NPD.
PMID- 27488699
TI - The association of DENND1A gene polymorphisms and polycystic ovary syndrome risk:
a systematic review and meta-analysis.
AB - PURPOSE: Polycystic ovary syndrome is heterogeneity disease, and the association
with DEEND1A gene has been discussed incompatibly for a long time. We conducted a
meta-analysis to evaluate the rs10818854, rs2479106, and rs10986105 polymorphism
in DENND1A gene with PCOS susceptibility. METHODS: Meta-analysis was performed
for common allele versus rare allele using random effect model on published
papers from January 1, 1980 to October 1, 2015. Subgroup analysis, sensitivity
analysis and publication bias were also carried out ultimately. The combined odds
ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the
strength of the association. RESULTS: The results showed that rs10818854 (OR =
1.36, 95 % CI 1.12-1.61) and rs10986105 (OR = 1.39, 95 % CI 1.20-1.58)
polymorphism increased the risk of PCOS probably. A significant association was
also found between rs2479106 mutation and Asian PCOS patients but not Europeans
(OR = 1.32, 95 % CI 1.25-1.39; OR = 1.01, 95 % CI 0.97-1.05, respectively).
CONCLUSIONS: In conclusion, the DENND1A gene variant is likely to have influence
on PCOS risk. Further studies are warranted to assess these associations in
greater detail, especially in different populations and different subtype of PCOS
patients.
PMID- 27488700
TI - Determinants of cumulative ART live-birth rates in a single-center study: age,
fertilization modality, and first-cycle outcome.
AB - PURPOSE: To analyze cumulative and single-cycle success rates of IVF and
intracytoplasmic sperm injection (ICSI) separately in relation to female age,
fertilization modality, and first-cycle outcome. METHODS: The study involved 2997
patients and couples, respectively, who underwent 5339 fresh and 3006 cryo cycles
using pronuclear-stage oocytes. Fertilization was achieved by the conventional
IVF or ICSI. Because of legal restrictions in Germany, no embryo selection was
performed. All cycles were documented prospectively. Kaplan-Meier survival rates
were calculated for all treatment cycles and transferred embryos. RESULTS:
Essentially, the success of assisted reproductive technology (ART) depends on a
woman's age and on skilful counselling. Cumulative pregnancy and live-birth rates
are the best indicators of successful ART. Probably for the first time, we
determined these cumulative rates separately for IVF and ICSI, and found them to
be almost identical. Live-birth rates reached 70-95 %, except for women aged over
40 years, whose chances of life birth are limited to about 25 %. Live-birth rate
per retrieval was 25.61 % for IVF and 26.3 % for ICSI. Time to pregnancy was
shorter for women who underwent a successful treatment in their first cycle.
CONCLUSIONS: The primary intention for the choice of fertilization modality
between IVF and ICSI is the prevention of a relative or total fertilization
failure. Such treatment failure is best prevented through ICSI, which results in
slightly higher clinical pregnancy rates per started cycle. After embryo
transfer, there are no differences in the success rates of IVF and ICSI. The
supposed cumulative live-birth rates are useful as a basis for counselling
subfertile couples to help reduce the high discontinuation rate, which is still
the main reason for inefficacy in ART. Following an unsuccessful first treatment
cycle, the prognosis remains positive, but until success is achieved, more
treatment cycles are necessary.
PMID- 27488701
TI - A comparison among different methods of letrozole combined with gonadotropin in
an antagonist protocol and high-dose gonadotropin ovarian stimulation antagonist
protocol in poor ovarian responders undergoing in vitro fertilization.
AB - PURPOSE: This study aimed at comparing the effects of different methods of
letrozole combined with gonadotropin (Gn) and high-dose Gn ovarian stimulation in
antagonist protocol. METHODS: Retrospectively reviewed 220 poor responders from
August 2012 to July 2014 at Peking University Third Hospital Reproductive Medical
Center. Patients were divided into Group 1 (LZ 5 mg for 5 days sequentially
overlapping with Gn cycles; n = 60), group 2 (LZ 7.5 mg for 3 days sequentially
with Gn cycles; n = 60), and group 3 (high-dose Gn cycles; n = 100). We compared
the basic status of patients and clinical outcomes of the three groups. RESULTS:
Basic characteristics of patients were comparable among groups. Group 1 had
significantly higher LH levels on day 7 and hCG than Group 2 and 3 (P < 0.05).
Group 1 had significantly higher early LH elevation rate (>20 IU/L) on the hCG
day than Groups 2 and 3 (11.7 vs. 6.7 and 2.0 %; P < 0.05). The amount of Gn used
in LZ groups was significantly lower than Group 3 (P < 0.01). However, the
clinical pregnancy rate and live birth rate were comparable among groups.
CONCLUSION: In conclusion, the LZ/antagonist protocol is a cost-effective and
patient friendly protocol, LZ 5 mg for 5 days sequentially overlapping with Gn
protocol has comparable pregnancy outcomes, and LZ 7.5 mg for 3 days sequentially
with the Gn protocol even has better clinical outcomes when compared with the
standard GnRH antagonist protocol in poor responders. LZ 7.5 mg for 3 days
sequentially with the Gn protocol appeared to have resulted in fewer improper LH
surges and better outcomes than LZ 5 mg for 5 days sequentially overlapping with
Gn in antagonist protocol.
PMID- 27488702
TI - Validation of the distress and impact thermometer and the changes of mood during
the first 6 months of treatment in gynecological cancer patients: a Kansai
Clinical Oncology Group (KCOG)-G1103 prospective study.
AB - PURPOSE: To verify distress and impact thermometer (DIT) for screening emotional
distress in gynecological cancer patients by Hospital Anxiety and Depression
Scale total (HADS-T) as gold standard and to assess emotional changes by DIT and
HADS-T. METHODS: A prospective study was conducted in newly diagnosed
gynecological cancer patients during the peri-treatment period after the cancer
diagnosis followed by 6-month. We defined a HADS-T score of >=11 as being
indicative of emotional distress. RESULTS: 117 patients were enrolled between May
1, 2011 and March 31, 2012, and 95 were eligible. The median age was 54 years
(range 31-77). (1) From the baseline to 3-month, distress (DIT-D) >=4 with Impact
(DIT-I) >=2 exhibited sensitivity, specificity, positive predictive value (PPV),
and negative predictive values (NPV) of 0.776 [95 % confidential interval (CI)
0.688, 0.850], 0.889 (95 % CI 0.824, 0.954), 0.868 (95 % CI 0.792, 0.949), and
0.808 (95 % CI 0.731, 0.886), respectively. (2) At 6-month, DIT-D >=2 with DIT-I
>=1 exhibited sensitivity, specificity, PPV and NPV of 0.893 (95 % CI 0.778, 1),
0.825 (95 % CI 0.707, 0.942), 0.781 (95 % CI 0.638, 0.928), and 0.917 (95 % CI
0.826, 1). (3) At 6-month, the HADS-T, DIT-D, and DIT-I scores in individual
patients were significantly reduced by a mean of 4.57 (p < 0.0001), 2.34 (p <
0.0001), and 1.10 (p = 0.0031), respectively, compared with those scores of
baseline (Student's paired t test), but still remained high. CONCLUSIONS: (1) On
acute phase within 3-month setting, DIT; DIT-D >=4 with DIT-I >=2, is a reliable
cut-off to screen emotional distress among gynecological cancer patients. (2) The
patients' moods had improved, but not completely recovered at 6-month after the
diagnosis.
PMID- 27488703
TI - Self-expanding plastic stent for esophageal leaks and fistulae.
AB - BACKGROUND: Self-expanding plastic stents (SEPS) have emerged as a good
alternative to surgery in esophageal leaks and fistulae. There is scarce
published literature regarding its efficacy in these conditions. We present our
experience with SEPS in treatment of esophageal leaks and fistulae. METHODS:
Consecutive patients admitted in a tertiary referral center who underwent SEPS
placement for esophageal leak or fistula between February 2012 and February 2015
were retrospectively evaluated. Patients underwent prior assessment with upper
gastrointestinal endoscopic and thoracic contrast-enhanced computed tomography
assessment. SEPS (25-mm flares, 21-mm diameter) were placed under fluoroscopic
guidance. A silk thread tied to upper end was routed through nostril and fixed to
prevent stent migration. Nasojejunal tube was inserted in all patients.
Intercostal drain was inserted in the case of hydro/pyopneumothorax. RESULTS:
Twelve patients [eight male, median age 45.3 years (19 to 65 years)] were
included. Etiologies were spontaneous leaks due to Boerhaave syndrome (n = 2),
corrosive fistulae (n = 2), tubercular fistulae (n = 4), invasive Candida
esophagitis-induced fistula (n = 1), iatrogenic leaks (n = 2; one achalasia
dilatation, one obesity surgery), and pancreaticoesophageal fistula due to
ruptured pancreatic pseudocyst (n = 1). Stent placement was successful in all
patients with no immediate postprocedure complications. Successful healing was
seen in nine patients (75 %). Stents were removed after a median time of 83.5
days (13-190 days). Stent migration was seen in four patients (33.3 %), and in
two of them, it was retrieved and redeployed; none had early migration (<72 h).
Reasons for SEPS failure in our cohort were failure of effective sepsis control
in two patients and poor wound healing seen in one patient having multiple
tubercular fistulae. CONCLUSION: SEPS is a safe, well-tolerated treatment with
good success rate (75 %) in treatment of esophageal leaks and fistulae.
PMID- 27488704
TI - Removal of multi-dye wastewater by the novel integrated adsorption and Fenton
oxidation process in a fluidized bed reactor.
AB - Traditionally, a few processes have to be employed in sequence for multi-dye
removal, due to the different physical and chemical characteristics of the dyes.
In this study, we innovatively developed an integrated adsorption and Fenton
oxidation fluidized bed reactor (FBR) based on the hydraulic classification
theory, which could efficiently remove dispersed red, acid yellow, and reactive
brilliant dyes. The fluidized solids such as ceramsite and activated carbon could
be separately fluidized at the bottom and the top part of the FBR, respectively.
As a result, Fenton oxidization of dyes was promoted by the fluidization of
ceramsite and activated carbon. Besides, adsorption of activated carbon could
synergistically act on the dyes. The results showed that the removal efficiencies
of acid yellow 2G, disperse red 60, and reactive brilliant blue X-BR could reach
100, 79.8, and 84.9 % in 10 min, respectively. Lots of intermediates with
unsaturated bonds were generated during Fenton reaction, which was further
removed by adsorption of activated carbon. Consequently, a high COD removal of 93
% was obtained. Interestingly, some of Fe3+ produced during Fenton reaction was
further precipitated and crystallized as FeO(OH) or Fe(OH)3 on the surface of
activated carbon and ceramsite, which could be potentially recycled for further
utilization as a heterogeneous catalyst. Meanwhile, the other Fe3+ might be
removed in the form of ferro-organic complexes by adsorption onto the activated
carbon. Thus, only a little iron hydroxide sludge was generated in the FBR. This
novel FBR gave us an effective clue to realize multi-reactions for textile
wastewater treatment by employing hydraulic classification fluidization.
PMID- 27488705
TI - Biodegradable packaging materials conception based on starch and polylactic acid
(PLA) reinforced with cellulose.
AB - The plastic materials used for packaging are increasing leading to a considerable
amount of undegradable solid wastes. This work deals with the reduction of
conventional plastics waste and the natural resources preservation by using
cellulosic polymers from renewable resources (alfa and luffa). Plasticized starch
films syntheses were achieved at a laboratory scale. These natural films showed
some very attractive mechanical properties at relatively low plasticizers levels
(12 to 17 % by weight). Furthermore, mixtures including polylactic acid polymer
(PLA) and cellulose fibers extracted from alfa and luffa were investigated by
melt extrusion technique. When used at a rate of 10 %, these fibers improved the
mixture mechanical properties. Both developed materials were biodegradable, but
the plasticized starch exhibited a faster biodegradation kinetic compared to the
PLA/cellulose fibers. These new materials would contribute to a sustainable
development and a waste reduction.
PMID- 27488706
TI - Stoichiometry evaluation of biohydrogen production from various carbohydrates.
AB - In this paper, biochemical hydrogen potential (BHP) tests were conducted to
investigate H2 production from different substrate with acid-treated anaerobic
digested sludge at the mesophilic range. The sludge was collected from an
anaerobic digester and was subjected to sulfuric acid pretreatments at pH 3 for
24 h. The effects of substrate type (glucose, fructose, and sucrose as carbon
source) were investigated in batch experiments. Results showed that substrate
degradation rate for all of the substrates was up 95 % and the electron
equivalent balance showed good closure for glucose and sucrose. Batch experiments
showed that the maximum molar hydrogen yield with glucose, fructose, and sucrose
was 3.27, 3.16, and 6.46 mol H2/mol of substrate. The maximum cumulative
biohydrogen production was 1552, 1487, and 1366 mL and maximum hydrogen
production rate was 308, 279, and 275 mL/h for glucose, sucrose, and fructose,
respectively. The experimental results suggest that the formation of hydrogen
associates with the main aqueous products, i.e., acetate butyrate.
PMID- 27488707
TI - Efficient decomposition of perchlorate to chloride ions in subcritical water by
use of steel slag.
AB - Decomposition of perchlorate (ClO4-) in subcritical water in the presence of
steel slag, a by-product of the steel industry, was investigated. Reactivity of
ClO4- was low in pure subcritical water state up to 300 degrees C, whereas
adding steel slag efficiently accelerated the decomposition of ClO4- to Cl-, with
no leaching of heavy metals such as chromium and other environmentally
undesirable elements (boron and fluorine). When the reaction was performed in
subcritical water at a relatively low temperature (250 degrees C) for 6 h,
virtually all ClO4- ions were removed from the reaction solution. The
concentration of Cl- after the reaction was well accounted for by the sum of the
amount of Cl- ascribed to the decomposition of ClO4- and the amount of Cl-
leached from the slag. This method was successfully applied to decompose ClO4- in
water samples collected from a man-made reflection pond following a fireworks
display, even though these samples contained much higher concentrations of Cl-
and SO42- than ClO4-.
PMID- 27488708
TI - The assessment of health impacts and external costs of natural gas-fired power
plant of Qom.
AB - The external health damage costs of the combined cycle natural gas-fired power
plant of Qom were investigated via the simplified impact pathway approach.
Emitted particulate matter (PM10) and gaseous pollutants (NO x , CO, and SO2)
from the power plant stack were measured The health effects and related costs
were estimated by QUERI model from AirPacts according to the emissions, source
and stack parameters, pollutant depletion velocities, exposure-response
functions, local and regional population density, and detailed meteorological
data. The results showed that the main health effect was assigned to the nitrate
as restricted activity days (RAD) with 25,240 days/year. For all pollutants, the
maximum health damage costs were related to the long-term mortality (49 %),
restricted activity days (27 %), and chronic bronchitis (21 %). The annual health
damage costs were approximately 4.76 million US$, with the cost being 0.096 US
per kWh of generating electricity. Although the health damage costs of gas-fired
power plant were lower than those of other heavy fuels, it seems essential to
consider the health and environmental damages and focus on the emission control
strategies, particularly in site selection for the new power plants and expanding
the current ones.
PMID- 27488709
TI - Drugs of environmental concern modify Solea senegalensis physiology and
biochemistry in a temperature-dependent manner.
AB - The alerted presence in recent decades of pharmaceuticals has become an issue of
environmental concern, and most of the mechanisms of biotransformation and
biochemical and physiological responses to them in fish are still unknown, as
well as the influence of water temperature in their ability to cope with them.
This study aims to detect the main effects of two of the most widespread drugs on
a set of physiological and biochemical markers in Solea senegalensis. Sole
juveniles acclimatized at 15 and 20 degrees C were administered an
intraperitoneal injection of the non-steroidal anti-inflammatory drug ibuprofen
(IB; 10 mg/kg) and the anti-convulsant drug carbamazepine (CBZ; 1 mg/kg). Two
days after the injection, liver, muscle and plasma were sampled. Liver enzymatic
activities of 15 degrees C acclimated fish were more responsive to
pharmaceuticals than those acclimated at 20 degrees C, especially for CYP450
related activities (7-ethoxyresorufin (EROD), 7-methoxyresorufin (MROD), 3-cyano
7-ethoxycoumarin (CECOD) and 7-benzyloxy-4-[trifluoromethyl]-coumarin-O
debenzyloxylase (BFCOD)) and uridine diphosphate glucuronosyltransferase (UDPGT).
Cytosolic anti-oxidant enzyme activities and glutathione S-transferase (GST) did
not show a clear effect of temperature. Glucose and transferase activities in
plasma were not affected by the treatments, while ammonium, osmolality and
lactate were affected by both pharmaceuticals. Plasma triglycerides were affected
in a temperature-dependent manner, and creatinine was only responsive to CBZ
injection. HSP70 levels in muscle were only affected by CBZ injection. Some of
the physiological identified responses to IB and CBZ are proposed as endpoints in
further chronic studies.
PMID- 27488710
TI - Oxidative stress in two tropical species after exposure to diesel oil.
AB - Recent offshore petroleum exploration has increased the risks of oil spills
worldwide. We investigated biomarker responses to diesel oil exposure in two
tropical and subtropical species, the clam Anomalocardia flexuosa and the
polychaete Laeonereis culveri. Animals were exposed to oil-spiked sediment at two
different concentrations (0.5 L and 1.0 L m-2). Activities of antioxidant enzymes
catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx);
glutathione transferase (GST); and lipid peroxides (LPO) were assessed in bivalve
digestive glands and polychaete whole-body homogenates at 36 and 60 h of
exposure. Significant variation in enzymatic antioxidant activity depended on the
sampling time after exposure. No similar response patterns, either increases or
decreases, were detected for the two target species, and biomarker responses were
species-specific. L. culveri showed clearer patterns in its antioxidant response
and should be prioritized over other species in biomonitoring studies involving
oil exposure. Understanding the temporal variability of these biomarkers is a
necessary action before implementing them as indicators measures in oil
contamination biomonitoring programs. Our results provide a better understanding
of biomarker responses in subtropical species, evidencing their potential use as
sentinels of oil contamination.
PMID- 27488711
TI - Moringa oleifera-mediated coagulation of textile wastewater and its
biodegradation using novel consortium-BBA grown on agricultural waste substratum.
AB - Generation of secondary sludge is a major concern of textile dye removal by
coagulation process. Combinatorial coagulation-biodegradation treatment system
has been found efficient in degradation of coagulated textile dye sludge. Moringa
oleifera seed powder (700 mg L-1) was able to coagulate textile dyestuff from
real textile wastewater with 98 % color removal. Novel consortium-BBA was found
to decolorize coagulated dye sludge. Parameters that significantly affect
coagulation process were optimized using response surface methodology. The bench
scale stirred tank reactor (50-L capacity) designed with optimized parameters for
coagulation process could efficiently remove 98, 89, 78, and 67 % of American Dye
Manufacturer's Institute (ADMI) in four repetitive cycles, respectively. Solid
state fermentation composting reactor designed to treat coagulated dye sludge
showed 96 % removal of dye within 10 days. Coagulation of dyes from textile
wastewater and degradation of coagulated dye sludge were confirmed by Fourier
transform infrared spectroscopy (FTIR) analysis. Cell morphology assay, comet
assay, and phytotoxicity confirmed the formation of less toxic products after
coagulation and degradation mechanism.
PMID- 27488712
TI - Organic acid compounds in root exudation of Moso Bamboo (Phyllostachys pubescens)
and its bioactivity as affected by heavy metals.
AB - Moso bamboo (Phyllostachys pubescens) has great potential as phytoremediation
material in soil contaminated by heavy metals. A hydroponics experiment was
conducted to determine organic acid compounds of root exudates of lead- (Pb),
zinc- (Zn), copper- (Cu), and cadmium (Cd)-tolerant of Moso bamboo. Plants were
grown in nutrients solution which included Pb, Zn, Cu, and Cd applied as Pb(NO3)2
(200 MUM), ZnSO4.7H2O (100 MUM), CuSO4.5H2O (25 MUM), and CdCl2 (10 MUM),
respectively. Oxalic acid and malic acid were detected in all treatments. Lactic
acid was observed in Cu, Cd, and control treatments. The oxalic was the main
organic acid exudated by Moso bamboo. In the sand culture experiment, the Moso
bamboo significantly activated carbonate heavy metals under activation of roots.
The concentration of water-soluble metals (except Pb) in sand were significantly
increased as compared with control. Organic acids (1 mM mixed) were used due to
its effect on the soil adsorption of heavy metals. After adding mixed organic
acids, the Cu and Zn sorption capacity in soils was decreased markedly compared
with enhanced Pb and Cd sorption capacity in soils. The sorption was analyzed
using Langmuir and Freundlich equations with R 2 values that ranged from 0.956 to
0.999 and 0.919 to 0.997, respectively.
PMID- 27488713
TI - Exploring the potential of fungi isolated from PAH-polluted soil as a source of
xenobiotics-degrading fungi.
AB - The aim of this study was to find polycyclic aromatic hydrocarbon (PAH)-degrading
fungi adapted to polluted environments for further application in bioremediation
processes. In this study, a total of 23 fungal species were isolated from a
historically pyrogenic PAH-polluted soil in Spain and taxonomically identified.
The dominant groups in these samples were the ones associated with fungi
belonging to the Ascomycota phylum and two isolates belonging to the
Mucoromycotina subphylum and Basiodiomycota phylum. We tested their ability to
convert the three-ring PAH anthracene in a 42-day time course and analysed their
ability to secrete extracellular oxidoreductase enzymes. Among the 23 fungal
species screened, 12 were able to oxidize anthracene, leading to the formation of
9,10-anthraquinone as the main metabolite, a less toxic one than the parent
compound. The complete removal of anthracene was achieved by three fungal
species. In the case of Scopulariopsis brevicaulis, extracellular enzyme
independent degradation of the initial 100 MUM anthracene occurred, whilst in the
case of the ligninolytic fungus Fomes (Basidiomycota), the same result was
obtained with extracellular enzyme-dependent transformation. The yield of
accumulated 9,10-anthraquinone was 80 and 91 %, respectively, and Fomes sp. could
slowly deplete it from the growth medium when offered alone. These results are
indicative for the effectiveness of these fungi for pollutant removal. Graphical
abstract ?.
PMID- 27488714
TI - Bioremediation of domestic and industrial wastewaters integrated with enhanced
biodiesel production using novel oleaginous microalgae.
AB - The study illustrates the synergistic potential of novel microalgal,
Chlamydomonas debaryana IITRIND3, for phycoremediation of domestic, sewage, paper
mill and dairy wastewaters and then subsequent utilisation of its biomass for
biodiesel production. Among these wastewaters, maximum lipid productivity (87.5
+/- 2.3 mg L-1 day-1) was obtained in dairy wastewater with removal efficiency of
total nitrogen, total phosphorous, chemical oxygen demand and total organic
carbon to be 87.56, 82.17, 78.57 and 85.97 %, respectively. Metal ions such as
sodium, calcium, potassium and magnesium were also removed efficiently from the
wastewaters tested. Pigment analysis revealed loss of chlorophyll a while
increase in carotenoid content in algal cells cultivated in different
wastewaters. Biochemical data of microalgae grown in different wastewaters showed
reduction in protein content with an increase in carbohydrate and lipid contents.
The major fatty acids in algal cells grown in dairy wastewater were C14:0, C16:0,
C16:1, C18:0, C18:2 and C18:3. The physical properties of biodiesel derived from
microalgae grown in dairy wastewater were in compliance with the ASTM D6751 and
EN 14214 fuel standards and were comparable to plant oil methyl esters.
PMID- 27488715
TI - Critical nutrient thresholds needed to control eutrophication and synergistic
interactions between phosphorus and different nitrogen sources.
AB - Eutrophication is one of the greatest threats to global freshwater ecosystems.
The phytoplankton responses to nutrient inputs vary in different water bodies, so
it is particularly important to determine the nutrient thresholds and synergistic
interactions between nutrients in different freshwater ecosystems. Field sampling
and bioassay experiments were conducted to determine the thresholds of soluble
reactive phosphorus (SRP), nitrate-nitrogen (NO3-N), and ammonium-nitrogen (NH4
N) in Miyun Reservoir. A separate nutrient addition bioassay was designed to
assess the synergistic interactions between these nutrients. Chlorophyll a (Chl
a) concentrations were used to estimate phytoplankton biomass. The results showed
the following: (1) nutrient threshold bioassay indicated that eutrophication
thresholds of SRP, NO3-N, and NH4-N should be targeted at below 0.04 mg P L-1,
0.5 mg N L-1, and 0.3 mg N L-1, respectively, to limit the growth of
phytoplankton. (2) The stimulatory effect of "NH4-N plus P" on phytoplankton
biomass was greater than "NO3-N plus P" at the same N concentration, and "NH4-N
plus NO3-N" did not show such associated stimulatory effect as "NH4-N plus P" or
"NO3-N plus P". (3) The average concentrations of total phosphorus (TP), NO3-N,
and NH4-N in Miyun Reservior were 0.017 mg P L-1, 0.620 mg N L-1, and 0.143 mg N
L-1, respectively. The reservoir-wide average Chl a is below 20 MUg L-1 on an
annual basis. (4) Ammonium was an important factor for the growth of
phytoplankton and inputs of both NH4-N and NO3-N should be reduced to control
bloom formation. Our findings imply that although P load reduction is important,
appropriate reductions of all forms of N in watershed is recommended in the
nutrient management strategy for Miyun Reservoir.
PMID- 27488716
TI - Interactions and accumulation differences of metal(loid)s in three sea cucumber
species collected from the Northern Mediterranean Sea.
AB - This study was conducted on Holothuria polii, Holothuria tubulosa, and Holothuria
mammata collected from five stations with different depths in the Northern
Mediterranean Sea. The body walls and guts of these holothurians were examined in
terms of interactions of 10 metals (iron (Fe), copper (Cu), manganese (Mn), zinc
(Zn), chromium (Cr), cobalt (Co), vanadium (V), nickel (Ni), cadmium (Cd), and
lead (Pb)) and one metalloid (arsenic (As)) using a multivariate analysis, and
interspecies differences were determined. The multivariate analysis of variance
(MANOVA) revealed significant differences between the species in terms of
metal(loid) accumulations. The principal component analysis (PCA) showed a more
association between H. tubulosa and H. polii with regard to the accumulation. The
cluster analysis (CA) located Pb concentrations of the guts to the farthest place
from all elements regardless of the species. A correlation analysis displayed
that the element concentrations of the guts were more closely related to each
other compared with those of the walls. The most inconsistent element in terms of
correlations was the gut Fe contents. Accordingly, while Fe concentrations of H.
mammata and H. tubulosa were correlated with all elements (except Pb) in divalent
metal transporter 1 (DMT1) (divalent cation transporter 1 (DCT1) or natural
resistance-associated macrophage protein 2 (NRAMP2)) belonging to the NRAM
protein family, this was not the case in H. polii. Consequently, significant
relationships between accumulated metal(loid)s that changed by tissues and sea
cucumber species were observed.
PMID- 27488717
TI - Analytical tools employed to determine pharmaceutical compounds in wastewaters
after application of advanced oxidation processes.
AB - Today, the presence of contaminants in the environment is a topic of interest for
society in general and for the scientific community in particular. A very large
amount of different chemical substances reaches the environment after passing
through wastewater treatment plants without being eliminated. This is due to the
inefficiency of conventional removal processes and the lack of government
regulations. The list of compounds entering treatment plants is gradually
becoming longer and more varied because most of these compounds come from
pharmaceuticals, hormones or personal care products, which are increasingly used
by modern society. As a result of this increase in compound variety, to address
these emerging pollutants, the development of new and more efficient removal
technologies is needed. Different advanced oxidation processes (AOPs), especially
photochemical AOPs, have been proposed as supplements to traditional treatments
for the elimination of pollutants, showing significant advantages over the use of
conventional methods alone. This work aims to review the analytical methodologies
employed for the analysis of pharmaceutical compounds from wastewater in studies
in which advanced oxidation processes are applied. Due to the low concentrations
of these substances in wastewater, mass spectrometry detectors are usually chosen
to meet the low detection limits and identification power required. Specifically,
time-of-flight detectors are required to analyse the by-products.
PMID- 27488718
TI - Integrated expanded granular sludge bed and sequential batch reactor treating
beet sugar industrial wastewater and recovering bioenergy.
AB - The exponential rise in energy demand vis-a-vis depletion of mineral oil
resources has accelerated recovery of bioenergy from organic waste. In this
study, a laboratory-scale anaerobic (An)/aerobic (Ar) system comprising of
expanded granular sludge bed (EGSB) reactor coupled to an aerobic sequential
batch reactor (SBR) was constructed to treat beet sugar industrial wastewater
(BSIW) of chemical oxygen demand (COD) 1665 mg L-1 while harnessing methane gas.
The EGSB reactor generated methane at the rate of 235 mL/g COD added, with
considerably higher than previously reported methane content of 86 %. Meanwhile,
contaminants were successfully reduced in the combined An/Ar system, realizing a
removal rate of more than 71.4, 97.3, 97.7, and 99.3 % of organic matter as total
phosphorus, total nitrogen, biological oxygen demand (BOD), and soluble COD,
respectively. Microbial community analysis showed that the bacterial genus
Clostridium sp. and archaeal genus Methanosaeta sp. dominated the EGSB reactor,
while Rhodobacter sp. dominance was observed in the SBR. The obtained
experimental results indicate that the integration of expanded granular sludge
bed and sequential batch reactor in treating BSIW obtained competitively
outstanding performance.
PMID- 27488719
TI - Is CO2 emission a side effect of financial development? An empirical analysis for
China.
AB - Based on panel data for 29 Chinese provinces from 1995 to 2012, this paper
explores the relationship between financial development and environmental quality
in China. A comprehensive framework is utilized to estimate both the direct and
indirect effects of financial development on CO2 emissions in China using a
carefully designed two-stage regression model. The first-difference and
orthogonal-deviation Generalized Method of Moments (GMM) methods are used to
control for potential endogeneity and introduce dynamics. To ensure the
robustness of the estimations, two indicators measuring financial development
financial depth and financial efficiency-are used. The empirical results indicate
that the direct effects of financial depth and financial efficiency on
environmental quality are positive and negative, respectively. The indirect
effects of both indicators are U shaped and dominate the shape of the total
effects. These findings suggest that the influences of the financial development
on environment depend on the level of economic development. At the early stage of
economic growth, financial development is environmentally friendly. When the
economy is highly developed, a higher level of financial development is harmful
to the environmental quality.
PMID- 27488720
TI - Improving sensitivity for microchip electrophoresis interfaced with inductively
coupled plasma mass spectrometry using parallel multichannel separation.
AB - We reported sensitivity enhancement using multichannel parallel separation for
microchip electrophoresis hyphenated with inductively coupled plasma mass
spectrometry (MCE-ICP-MS) in this study. By using 2-20 array lanes for parallel
separation, the sensitivity of the MCE-ICP-MS system was proportionally improved
by 2-20 folds. No significantly adverse effect of parallel separation on column
efficiency and resolution was observed. Rapid separation of Hg(2+) and
methylmercuric (MeHg) ion within 36s under an electric field of 800Vcm(-1) was
achieved in the 2-cm twenty-channels with a background electrolyte of 5mmolL(-1)
borate buffer (pH 9.2). Detection limits of Hg(2+) and MeHg by the proposed
system were decreased to 6.8-7.1ngL(-1). Good agreement between determined values
and certified values of a certified reference fish was obtained with recoveries
ranged between 94-98%. All results prove its advantages including high
sensitivity, high efficiency and low operation cost, which are beneficial to
routine analysis of metal speciation in environmental, biological and food
fields.
PMID- 27488721
TI - Characterization of sulfur and nitrogen compounds in Brazilian petroleum
derivatives using ionic liquid capillary columns in comprehensive two-dimensional
gas chromatography with time-of-flight mass spectrometric detection.
AB - Diesel and naphtha samples were analyzed using ionic liquid (IL) columns to
evaluate the best column set for the investigation of organic sulfur compounds
(OSC) and nitrogen(N)-containing compounds analyses with comprehensive two
dimensional gas chromatography coupled to time-of-flight mass spectrometry
detector (GC*GC/TOFMS). Employing a series of stationary phase sets, namely DB
5MS/DB-17, DB-17/DB-5MS, DB-5MS/IL-59, and IL-59/DB-5MS, the following parameters
were systematically evaluated: number of tentatively identified OSC, 2D
chromatographic space occupation, number of polyaromatic hydrocarbons (PAH) and
OSC co-elutions, and percentage of asymmetric peaks. DB-5MS/IL-59 was chosen for
OSC analysis, while IL59/DB-5MS was chosen for nitrogen compounds, as each
stationary phase set provided the best chromatographic efficiency for these two
classes of compounds, respectively. Most compounds were tentatively identified by
Lee and Van den Dool and Kratz retention indexes, and spectra-matching to
library. Whenever available, compounds were also positively identified via
injection of authentic standards.
PMID- 27488722
TI - Validation of the PECARN clinical decision rule for children with minor head
trauma: a French multicenter prospective study.
AB - BACKGROUND: To date, the Pediatric Emergency Care Applied Research Network
(PECARN) rule for identifying children who are at very low risk of clinically
important traumatic brain injuries after minor head trauma has not been validated
prospectively in an independent population. Our goal was to evaluate the
diagnostic performance of the PECARN clinical decision rule in a French pediatric
population in multiple clinical settings. METHODS: We conducted a multicenter,
prospective, non-interventional cohort study of patients with minor head trauma
who presented to three emergency departments in France. We enrolled patients
younger than 16 years of age seeking a consultation within 24 h of head trauma
with Glasgow Coma Scale scores of 14-15. RESULTS: During the study period, we
included 1499 children of which 421 (28 %) were under 2 years of age, and 955 (64
%) were male. A cranial computed tomography (CT) scan was performed on 76
patients (5.1 %). Of the 1499 included patients, 9 children (0.6 %) had a
clinically-important traumatic brain injury, and none were classified as very low
risk by the PECARN rule. In our study, the sensitivity of this clinical decision
rule was 100 % (95 % CI 66.4 to 100 %), the specificity was 69.9 % (95 % CI 67.5
to 72.2 %) and the negative predictive value was 100 % (95 % CI 99.7 to 100 %).
DISCUSSION: Our study confirmed the good predictive performances of the PECARN
clinical decision rule for minor head trauma in children. The PECARN rule
performed similarly to our study and to its internal validation study.
CONCLUSIONS: We conducted an external validation study of the PECARN clinical
decision rule for the detection of clinically-important traumatic brain injuries
in children with minor head trauma, according to the methodological standards.
The PECARN rule successfully identified all patients with clinically-important
traumatic brain injuries, with a limited use of CT scans. Conducting a broad
validation study with a large cohort is a prerequisite to provide sufficient
statistical power before authorizing its implementation and generalization. TRIAL
REGISTRATION: This study has been registered in ClinicalTrials.gov with
identifier number: NCT02752711 on April 27, 2016.
PMID- 27488723
TI - Internal and External Validation of a Computer-Assisted Surveillance System for
Hospital-Acquired Infections in a 754-Bed General Hospital in the Netherlands.
AB - OBJECTIVE To evaluate a computer-assisted point-prevalence survey (CAPPS) for
hospital-acquired infections (HAIs). DESIGN Validation cohort. SETTING A 754-bed
teaching hospital in the Netherlands. METHODS For the internal validation of a
CAPPS for HAIs, 2,526 patients were included. All patient records were
retrospectively reviewed in depth by 2 infection control practitioners (ICPs) to
determine which patients had suffered an HAI. Preventie van Ziekenhuisinfecties
door Surveillance (PREZIES) criteria were used. Following this internal
validation, 13 consecutive CAPPS were performed in a prospective study from
January to March 2013 to determine weekly, monthly, and quarterly HAI point
prevalence. Finally, a CAPPS was externally validated by PREZIES (Rijksinstituut
voor Volksgezondheid en Milieu [RIVM], Bilthoven, Netherlands). In all
evaluations, discrepancies were resolved by consensus. RESULTS In our series of
CAPPS, 83% of the patients were automatically excluded from detailed review by
the ICP. The sensitivity of the method was 91%. The time spent per hospital-wide
CAPPS was ~3 hours. External validation showed a negative predictive value of
99.1% for CAPPS. CONCLUSIONS CAPPS proved to be a sensitive, accurate, and
efficient method to determine serial weekly point-prevalence HAI rates in our
hospital. Infect Control Hosp Epidemiol 2016;1-6.
PMID- 27488724
TI - An In Vitro Model That Predicts the Therapeutic Efficacy of Immunomodulatory
Antibodies.
AB - Immunomodulatory monoclonal antibodies (mAbs) have efficacy in patients with
advanced cancer and are the focus of intensive research. However, cures are
infrequent and responses vary among tumor types and among subjects with the same
tumor. An in vitro test would be valuable to determine the most effective mAb
combination for a given case and to evaluate novel agents. Toward this goal, we
investigated the ability of various mAb combinations to generate a tumor
destructive immune response in vitro in the presence of lymphoid cells from mice
with established TC1 lung carcinoma, B16 melanoma, or SW1 melanoma. The data
strongly correlate (r=0.9, 0.89, and 0.91, respectively) with the therapeutic
efficacy of the respective mAb combinations. Both in vivo and in vitro, tumor
destruction was associated with a shift from a Th2 to a Th1 response and included
a dramatic increase of long-term memory cells. A combination of mAbs to CD137/PD
1/CTLA4/CD19 was most efficacious.
PMID- 27488725
TI - Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address
Safety and Toxicity Concerns.
AB - Advances in cancer immunotherapies utilizing engineered hematopoietic cells have
recently generated significant clinical successes. Of great promise are
immunotherapies based on chimeric antigen receptor-engineered T (CAR-T) cells
that are targeted toward malignant cells expressing defined tumor-associated
antigens. CAR-T cells harness the effector function of the adaptive arm of the
immune system and redirect it against cancer cells, overcoming the major
challenges of immunotherapy, such as breaking tolerance to self-antigens and
beating cancer immune system-evasion mechanisms. In early clinical trials, CAR-T
cell-based therapies achieved complete and durable responses in a significant
proportion of patients. Despite clinical successes and given the side effect
profiles of immunotherapies based on engineered cells, potential concerns with
the safety and toxicity of various therapeutic modalities remain. We discuss the
concerns associated with the safety and stability of the gene delivery vehicles
for cell engineering and with toxicities due to off-target and on-target, off
tumor effector functions of the engineered cells. We then overview the various
strategies aimed at improving the safety of and resolving toxicities associated
with cell-based immunotherapies. Integrating failsafe switches based on different
suicide gene therapy systems into engineered cells engenders promising strategies
toward ensuring the safety of cancer immunotherapies in the clinic.
PMID- 27488726
TI - Effects of SGLT-2 inhibitors on mortality and cardiovascular events: a
comprehensive meta-analysis of randomized controlled trials.
AB - AIMS: EMPAREG OUTCOME study showed a reduction in cardiovascular events in
patients treated with the sodium-glucose transporter 2 inhibitor (SGLT2i)
empagliflozin, as compared to placebo. Other drugs of the same class are
currently been investigated for cardiovascular outcomes. In the meanwhile, a re
analysis of data collected in available studies can add relevant insight.
METHODS: A MEDLINE search for SGLT-2 inhibitors (dapagliflozin, empagliflozin,
canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed,
collecting all randomized trials up to November 16, 2015. All trials with a
duration of treatment >=12 weeks, enrolling patients with type 2 diabetes,
comparing a SGLT2i with placebo or other comparators were included. The principal
outcome was the effect of SGLT2i on all-cause and cardiovascular mortality.
Secondary endpoints were myocardial infarction and stroke. Mantel-Haenszel odds
ratio with 95 % confidence interval (MH-OR) was calculated. RESULTS: A total of
71 trials were included (31,199 and 16,088 patients in SGLT2i and comparator
groups). Treatment with SGLT2i was associated with a significant reduction in all
cause mortality (MH-OR 0.70 [0.59-0.83], p < 0.001), cardiovascular mortality (MH
OR 0.43 [0.36-0.53], p < 0.001), and myocardial infarction (MH-OR 0.77 [0.63
0.94], p < 0.01), but not stroke (MH-OR 1.09 [0.86-1.38], p = 0.50), with no
apparent difference across molecules (after excluding cardiovascular outcome
trials). CONCLUSIONS: Available data suggest that the beneficial action observed
with empagliflozin on all-cause and cardiovascular mortality in EMPAREG OUTCOME
study is a class effect. The present meta-analysis showed a significantly
reduction in myocardial infarction, with no increased risk of stroke.
PMID- 27488727
TI - Replication of genome-wide association signals in Asian Indians with early-onset
type 2 diabetes.
AB - AIMS: To evaluate the association of 87 genetic variants previously associated
with type 2 diabetes mellitus (T2DM) in genome-wide association studies of
populations of European ancestry in an Asian Indian population with early-onset
type 2 diabetes mellitus (EOT2DM). METHODS: The study groups comprised of 877
type 2 diabetes individuals, 436 individuals with EOT2DM (age at diagnosis below
35 years), 441 individuals with older T2DM (diagnosis at 35 years or greater) and
controls with normal glucose tolerance (NGT) (n = 400 younger than 35 years; n =
438 older than 35 years). The participants were genotyped for 87 SNPs from 44
genes and 27 intergenic loci. Associations were tested using logistic regression.
RESULTS: All the variants in TCF7L2 and CDKN2A/2B showed study-wide significance
(p < 1.4 * 10-4) with T2DM, but only rs7903146, rs12243326, rs12255372 of TCF7L2
and rs7020996 of CDKN2A/2B showed study-wide significance (p < 1.4 * 10-4) with
EOT2DM in this population. In addition, an intergenic SNP on chromosome 1
(rs10493685) was also shown to be study-wide significant (p = 7.1 * 10-6).
Several additional SNPs previously associated with T2DM reached borderline
significance in this study, but may have been limited by relatively low sample
numbers. Various other SNPs of T2DM were not associated with EOT2DM. CONCLUSIONS:
Some of the variants in TCF7L2 and CDKN2A/2B associated with T2DM are associated
with EOT2DM as well. An intergenic SNP on chromosome 1p31 showed association only
with early-onset T2DM in this Asian Indian population. The lack of association
with many other SNPs of T2DM may be a reflection of the lack of power of the
study, sample size, differences in the frequencies of genetic polymorphisms in
different ethnic groups, effect sizes, as well as ancestral differences in
pattern of LD between the genetic variants involved in early- and late-onset
T2DM.
PMID- 27488728
TI - Mechanistic insights into the role of PC- and PCP-type palladium catalysts in
asymmetric hydrophosphination of activated alkenes incorporating potential
coordinating heteroatoms.
AB - The impact of the structural attributes of chiral PC- and PCP-palladium catalysts
was investigated in the asymmetric hydrophosphination of various heterocycle
functionalized enone substrates. Due to the architecture of the catalysts, they
are confronted with potential catalyst deactivation arising from the coordination
of the electron-rich heteroatoms (P, O, N and S) to the metal center. A
systematic variation of the location and identity of the heteroatoms demonstrated
the impact of structural modifications on the substrates, which have a
significant influence on both yields (16-99%) and enantioselectivities (0-99%). A
detailed discussion on the distinct catalytic mechanisms (intra- vs. inter
molecular addition) provides important information to explain the results
obtained.
PMID- 27488729
TI - The Pharmacological Costs of Complete Liver Resections in Unselected Advanced
Colorectal Cancer Patients: Focus on Targeted Agents. A Review of Randomized
Clinical Trials.
AB - BACKGROUND: The aim of this study was to evaluate the pharmacological costs of
conversion chemotherapy with targeted biological agents in an unselected
population of advanced colorectal cancer (CRC) patients in order to achieve an R0
liver resection. METHODS: Full reports and updates of randomized clinical trials
(RCTs) that compared at least two front-line therapy regimens with targeted
biological agents for advanced CRC patients were selected. The present evaluation
was restricted to randomized phase II and III trials. The costs of drugs are at
the Pharmacy Hospital and are expressed in euros (?). RESULTS: Our study began
with the evaluation of 683 abstracts. Forty-eight trials were considered
appropriate for further analysis. A more in-depth evaluation looking for the
trials reporting the liver resection rates following conversion chemotherapy
brought to the exclusion of other 37 trials, leaving 11 randomized trials (three
phase II trials, including 522 patients and eight phase III trials, including
7191 patients). The pharmacological costs of conversion therapy increased with
the substitution of prolonged infusion 5-Fluorouracil by capecitabine and, to a
much higher extent, with the introduction of biologicals. CONCLUSIONS: Two key
issues are presented in this review. First, the pharmacological costs of commonly
used front line regimens based on the targeted biological agents for the
treatment of advanced CRC are highly variable. Second, the performance of the
published schemes, in terms of resection rates, depends on patient's selection,
tumor characteristics, and on the type of the scheme.
PMID- 27488730
TI - Feasibility work to inform the design of a randomized clinical trial of wound
dressings in elective and unplanned abdominal surgery.
AB - BACKGROUND: Designing RCTs in surgery requires consideration of existing
evidence, stakeholders' views and emerging interventions, to ensure that research
questions are relevant to patients, surgeons and the health service. When there
is uncertainty about RCT design, feasibility work is recommended. This study
aimed to assess how feasibility work could inform the design of a future pilot
study and RCT (Bluebelle, HTA - 12/200/04). METHODS: This was a prospective
survey of dressings used to cover abdominal wounds. Surgical trainees from 25
hospitals were invited to participate. Information on patient risk factors,
operation type and type of wound dressings used was recorded for elective and
unplanned abdominal procedures over a 2-week interval. The types of dressing used
were summarized, and associations with operation type and patient risk factors
explored. RESULTS: Twenty hospitals participated, providing data from 727
patients (1794 wounds). Wounds were predominantly covered with basic dressings
(1203 of 1769, 68.0 per cent) and tissue adhesive was used in 27.4 per cent (485
of 1769); dressing type was missing for 25 wounds. Just 3.6 per cent of wounds
(63 of 1769) did not have a dressing applied at the end of the procedure. There
was no evidence of an association between type of dressing used and patient risk
factors, type of operation, or elective and unscheduled surgery. CONCLUSION:
Based on the findings from this large study of current practice, the pilot study
design has evolved. The inclusion criteria have expanded to encompass patients
undergoing unscheduled surgery, and tissue adhesive as a dressing will be
evaluated as an additional intervention group. Collaborative methods are
recommended to inform the design of RCTs in surgery, helping to ensure they are
relevant to current practice.
PMID- 27488733
TI - Supercritical Fluid Synthesis and Tribological Applications of Silver
Nanoparticle-decorated Graphene in Engine Oil Nanofluid.
AB - Silver nanoparticle-decorated graphene nanocomposites were synthesized by a
facile chemical reduction approach with the assistance of supercritical CO2
(ScCO2). The silver nanoparticles with diameters of 2-16 nm are uniformly
distributed and firmly anchored on graphene nanosheets. The tribological
properties of the as-synthesized nanocomposites as lubricant additives in engine
oil were investigated by a four-ball tribometer. The engine oil with 0.06~0.10
wt.% Sc-Ag/GN nanocomposites displays remarkable lubricating performance,
superior than the pure engine oil, the engine oil containing zinc dialkyl
dithiophosphate (ZDDP), as well as the oil dispersed with the single nanomaterial
of graphene oxides (GOs) and nano-Ag particles alone. The remarkable lubricating
behaviors of Sc-Ag/GN probably derive from the synergistic interactions of nano
Ag and graphene in the nanocomposite and the action of the formed protective film
on the contact balls. The anchored nano-Ag particles on graphene expand the
interlamination spaces of graphene nanosheets and can prevent them from
restacking during the rubbing process, resulting in the full play of lubricating
activity of graphene. The formed protective film on the friction pairs
significantly reduces the surface roughness of the sliding balls and hence
preventing them from direct interaction during the sliding process.
PMID- 27488732
TI - Ergonomic design and evaluation of a diagnostic ultrasound transducer holder.
AB - BACKGROUND: Work-related musculoskeletal disorders (WMSDs) are injuries and
disorders that affect the body's movement and musculoskeletal system. Awkward
postures represent one of the major ergonomic risk factors that cause WMSDs among
sonographers while working with an ultrasound transducer. This study aimed to
design and evaluate a new holder for the ultrasound transducer. MATERIALS AND
METHODS: In the first phase a new holder was designed for the transducer,
considering design principles. Evaluation of the new holder was then carried out
by electrogoniometry and a locally perceived discomfort (LPD) scale. RESULTS: The
application of design principles to the new holder resulted in an improvement of
wrist posture and comfort. Wrist angles in extension, flexion, radial deviation
and ulnar deviation were lower with utilization of the new holder. The severity
of discomfort based on the LPD method in the two modes of work with and without
the new holder was reported with values of 1.3 and 1.8, respectively (p < 0.05).
CONCLUSION: Overall, this study indicated that applying ergonomics design
principles was effective in minimizing wrist deviation and increasing comfort
while working with the new holder.
PMID- 27488731
TI - Sound tuning of amygdala plasticity in auditory fear conditioning.
AB - Various auditory tones have been used as conditioned stimuli (CS) for fear
conditioning, but researchers have largely neglected the effect that different
types of auditory tones may have on fear memory processing. Here, we report that
at lateral amygdala (LA) synapses (a storage site for fear memory), conditioning
with different types of auditory CSs (2.8 kHz tone, white noise, FM tone)
recruits distinct forms of long-term potentiation (LTP) and inserts calcium
permeable AMPA receptor (CP-AMPAR) for variable periods. White noise or FM tone
conditioning produced brief insertion (<6 hr after conditioning) of CP-AMPARs,
whereas 2.8 kHz tone conditioning induced more persistent insertion (>=6 hr).
Consistently, conditioned fear to 2.8 kHz tone but not to white noise or FM tones
was erased by reconsolidation-update (which depends on the insertion of CP-AMPARs
at LA synapses) when it was performed 6 hr after conditioning. Our data suggest
that conditioning with different auditory CSs recruits distinct forms of LA
synaptic plasticity, resulting in more malleable fear memory to some tones than
to others.
PMID- 27488734
TI - Effects of life-history requirements on the distribution of a threatened reptile.
AB - Survival and reproduction are the two primary life-history traits essential for
species' persistence; however, the environmental conditions that support each of
these traits may not be the same. Despite this, reproductive requirements are
seldom considered when estimating species' potential distributions. We sought to
examine potentially limiting environmental factors influencing the distribution
of an oviparous reptile of conservation concern with respect to the species'
survival and reproduction and to assess the implications of the species'
predicted climatic constraints on current conservation practices. We used
ecological niche modeling to predict the probability of environmental suitability
for the alligator snapping turtle (Macrochelys temminckii). We built an annual
climate model to examine survival and a nesting climate model to examine
reproduction. We combined incubation temperature requirements, products of
modeled soil temperature data, and our estimated distributions to determine
whether embryonic development constrained the northern distribution of the
species. Low annual precipitation constrained the western distribution of
alligator snapping turtles, whereas the northern distribution was constrained by
thermal requirements during embryonic development. Only a portion of the
geographic range predicted to have a high probability of suitability for
alligator snapping turtle survival was estimated to be capable of supporting
successful embryonic development. Historic occurrence records suggest adult
alligator snapping turtles can survive in regions with colder climes than those
associated with consistent and successful production of offspring. Estimated egg
incubation requirements indicated that current reintroductions at the northern
edge of the species' range are within reproductively viable environmental
conditions. Our results highlight the importance of considering survival and
reproduction when estimating species' ecological niches, implicating conservation
plans, and benefits of incorporating physiological data when evaluating species'
distributions.
PMID- 27488736
TI - A descriptive analysis of medical health services utilization of Veterans living
in Ontario: a retrospective cohort study using administrative healthcare data.
AB - BACKGROUND: Health services utilization by Veterans following release may be
different than the general population as the result of occupational conditions,
requirements and injuries. This study provides the first longitudinal overview of
Canadian Veteran healthcare utilization in the Ontario public health system.
METHODS: This is a retrospective cohort study designed to use Ontario's
provincial healthcare data to study the demographics and healthcare utilization
of Canadian Armed Forces (CAF) & RCMP Veterans living in Ontario. Veterans were
eligible for the study if they released between January 1, 1990 and March 31,
2013. Databases at the Institute for Clinical Evaluative Sciences were linked by
a unique identifier to study non-mental health related hospitalizations,
emergency department visits, and physician visits. Overall and age-stratified
descriptive statistics were calculated in five-year intervals following the date
of release. RESULTS: The cohort is comprised of 23, 818 CAF or RCMP Veterans.
Following entry into the provincial healthcare system, 82.6 % (95 % CI 82.1-83.1)
of Veterans saw their family physician at least once over the first five years
following release, 60.7 % (95 % CI 60.0-61.3) saw a non-mental health specialist,
40.8 % (95 % CI 40.2-41.5) went to the emergency department in that same time
period and 9.9 % (9.5-10.3) were hospitalized for non-mental health related
complaints. Patterns of non-mental health services utilization appeared to be
time and service dependant. Stratifying health services utilization by age of the
Veteran at entry into the provincial healthcare system revealed significant
differences in service use and intensity. CONCLUSION: This study provides the
first description of health services utilization by Veterans, following release
from the CAF or RCMP. This work will inform the planning and delivery of support
to Veterans in Ontario.
PMID- 27488737
TI - Sleep Quality: A Pilot Study Comparing Patients With and Without Injection
Related Venous Ulcers.
AB - PURPOSE: The purposes of this study were to (a) compare sleep quality of persons
with and without injection-related venous ulcers (VU) and (b) examine
associations between global sleep quality with age, sex, comorbidities, pain,
nutrition, physical health rating, fatigue, emotional problems, health-related
quality of life, attitude toward physical activity, and number of ulcers. DESIGN:
This study used a cross-sectional design. SUBJECTS AND SETTING: The participants
included 31 patients with VU and 30 without VU (men [n = 35] and women; mean age
= 54 years) who were attending an indigent clinic for wound care or general
health. METHODS: Participants were recruited from an urban clinic when they came
for primary care or wound care. Questionnaires were administered at that time and
included the Pittsburgh Sleep Quality Index (PSQI), Mini Nutrition Assessment,
Patient Reported Outcomes Measurement Information System (PROMIS) questions about
general physical health, fatigue, emotional problems, and quality of life, Brief
Pain Inventory worst pain rating, Positive Attitude and Motivation for Physical
Activity Scale, wound assessment, and demographic factors. RESULTS: The 2 groups
did not differ on the PSQI in terms of time going to bed, minutes to fall asleep,
time awakening, hours slept, and time in bed. Those with VU compared to without
VU took more medications to help sleep (P<= .03). There were no significant
differences in PSQI correlations across groups. All study variables except age,
gender, and quality of life were significantly related to Global sleep
disturbance score. A higher number of comorbid conditions, worse pain, poorer
nutrition, poor physical health rating, greater fatigue, more emotional problems,
and poor attitude toward physical activity were related to greater sleep
disturbances for all participants. Both groups had mean Global PSQI scores
greater than 5 (with VU = 7.83 and without VU = 8.2), indicating sleep problems.
CONCLUSIONS: Study findings suggest that sleep disturbances may be a concern in
persons with VU and are related to many variables. Assessing sleep along with
other aspects of wound care may provide a more comprehensive assessment of
factors affecting a person with a VU.
PMID- 27488735
TI - The impact of leadership hubs on the uptake of evidence-informed nursing
practices and workplace policies for HIV care: a quasi-experimental study in
Jamaica, Kenya, Uganda and South Africa.
AB - BACKGROUND: The enormous impact of HIV on communities and health services in Sub
Saharan Africa and the Caribbean has especially affected nurses, who comprise the
largest proportion of the health workforce in low- and middle-income countries
(LMICs). Strengthening action-based leadership for and by nurses is a means to
improve the uptake of evidence-informed practices for HIV care. METHODS: A
prospective quasi-experimental study in Jamaica, Kenya, Uganda and South Africa
examined the impact of establishing multi-stakeholder leadership hubs on evidence
informed HIV care practices. Hub members were engaged through a participatory
action research (PAR) approach. Three intervention districts were purposefully
selected in each country, and three control districts were chosen in Jamaica,
Kenya and Uganda. WHO level 3, 4 and 5 health care institutions and their
employed nurses were randomly sampled. Self-administered, validated instruments
measured clinical practices (reports of self and peers), quality assurance, work
place policies and stigma at baseline and follow-up. Standardised average scores
ranging from 0 to 1 were computed for clinical practices, quality assurance and
work place policies. Stigma scores were summarised as 0 (no reports) versus 1
(one or more reports). Pre-post differences in outcomes between intervention and
control groups were compared using the Mantel Haenszel chi-square for
dichotomised stigma scores, and independent t tests for other measures. For South
Africa, which had no control group, pre-post differences were compared using a
Pearson chi-square and independent t test. Multivariate analysis was completed
for Jamaica and Kenya. Hub members in all countries self-assessed changes in
their capacity at follow-up; these were examined using a paired t test. RESULTS:
Response rates among health care institutions were 90.2 and 80.4 % at baseline
and follow-up, respectively. Results were mixed. There were small but
statistically significant pre-post, intervention versus control district
improvements in workplace policies and quality assurance in Jamaica, but these
were primarily due to a decline in scores in the control group. There were modest
improvements in clinical practices, workplace policies and quality assurance in
South Africa (pre-post) (clinical practices of self-pre 0.67 (95 % CI, 0.62,
0.72) versus post 0.78 (95 % CI, 0.73-0.82), p = 0.002; workplace policies-pre
0.82 (95 % CI, 0.70, 0.85) versus post 0.87 (95 % CI, 0.84, 0.90), p = 0.001;
quality assurance-pre 0.72 (95 % CI, 0.67, 0.77) versus post 0.84 (95 % CI, 0.80,
0.88)). There were statistically significant improvements in scores for nurses
stigmatising patients (Jamaica reports of not stigmatising-pre-post intervention
33.9 versus 62.4 %, pre-post control 54.7 versus 64.4 %, p = 0.002-and Kenya pre
post intervention 35 versus 51.6 %, pre-post control 34.2 versus 47.8 %, p =
0.006) and for nurses being stigmatised (Kenya reports of no stigmatisation-pre
post intervention 23 versus 37.3 %, pre-post control 15.4 versus 27 %, p =
0.004). Multivariate results for Kenya and Jamaica were non-significant. Twelve
hubs were established; 11 were active at follow-up. Hub members (n = 34) reported
significant improvements in their capacity to address care gaps. CONCLUSIONS:
Leadership hubs, comprising nurses and other stakeholders committed to change and
provided with capacity building can collectively identify issues and act on
strategies that may improve practice and policy. Overall, hubs did not provide
the necessary force to improve the uptake of evidence-informed HIV care in their
districts. If hubs are to succeed, they must be integrated within district health
authorities and become part of formal, legal organisations that can regularise
and sustain them.
PMID- 27488738
TI - Adolescent Perspectives Following Ostomy Surgery: A Grounded Theory Study.
AB - PURPOSE: This purpose of this study was to provide a theoretical account of how
adolescents aged 13 to 18 years process the experience of having an ostomy.
DESIGN: Qualitative study using grounded theory design. SUBJECTS AND SETTING: The
sample comprised of 12 English-speaking adolescents aged 13-18 years: 10 with an
ostomy and 2 with medical management of their disease. METHODS: Respondents
completed audio-recorded interviews that were transcribed verbatim. Data were
analyzed using the constant comparative method until data saturation occurred.
Dedoose, a Web-based qualitative methods management tool, was used to capture
major themes arising from the data. RESULTS: Study results indicate that for
adolescents between 13 and 18 years of age, processing the experience of having
an ostomy includes concepts of the "physical self" and "social self" with the
goal of "normalizing." Subcategories of physical self include (a) changing
reality, (b) learning, and (c) adapting. Subcategories of social self include (a)
reentering and (b) disclosing. CONCLUSIONS: This study sheds light on how
adolescents process the experience of having an ostomy and how health care
providers can assist adolescents to move through the process to get back to their
desired "normal" state. Health care providers can facilitate the adolescent
through the ostomy experience by being proactive in conversations not only about
care issues but also about school and family concerns and spirituality. Further
research is needed in understanding how parents process their adolescents' ostomy
surgery experience and how spirituality assists adolescents in coping and
adjustment with body-altering events.
PMID- 27488739
TI - Incontinence-Associated Dermatitis (IAD).
PMID- 27488740
TI - Feasibility of a Web-Based Self-management Intervention for Intermittent Urinary
Catheter Users With Spinal Cord Injury.
AB - PURPOSE: The purpose of this study was to evaluate the feasibility of a new Web
based intermittent catheter self-management intervention. DESIGN: We tested the
acceptability and usability of intervention components, which included multiple
Web-based materials (an online urinary diary adapted for mobile phone use and an
educational booklet), 3 phone calls with a nurse, and a peer-led discussion
forum. SUBJECTS AND SETTING: Thirty adults with spinal cord injury using
intermittent catheterization for bladder drainage were enrolled; 26 participants
received the nurses' phone-based consultations. METHODS: Preliminary
effectiveness of new self-efficacy and self-management scales were evaluated
using baseline and 3-month online surveys. Participants' perceived value of the
intervention components, self-management changes, and suggestions were assessed
with data from the 3-month surveys, followed by brief tape-recorded interviews.
RESULTS: Several catheter practices improved somewhat over 3 months. The
frequency of catheterizations every 4 to 6 hours increased from 71% to 77%. Self
management of neurogenic bladder dysfunction increased significantly (P = .032);
participant comments indicated that fluid intake was the biggest change. Catheter
related self-efficacy and quality-of-life scores increased but not significantly.
The frequency of urinary tract infection and pain did not change significantly.
For feasibility, intervention components, with the exception of the forum, were
rated highly by the majority of participants for usefulness, satisfaction
(desired information), and Web-based usability. CONCLUSION: Further testing of
this intervention is recommended in a multisite randomized clinical trial.
PMID- 27488741
TI - [German national second-opinion network for testicular cancer and penile
carcinoma : Two sources for evidence-based information].
AB - BACKGROUND: The second-opinion network for testicular cancer is an internet-based
platform addressing physicians treating testicular cancer patients. They are
offered a second-opinion before determining further therapy after orchiectomy and
completion of staging. THEME: The high rate of discrepancies between the first
and second opinion in more than 30 % supports the assumption of a deficit in the
implementation of treatment guidelines. In 2015, approximately 22 % of the newly
diagnosed cases with testicular cancer in Germany were covered by this system.
According to the present interim analysis, the second-opinion platform helps to
avoid overtreatment of testicular cancer patients. The high acceptance of the
project and the encouraging results of this interim analysis gave rise to
considerations to apply the second-opinion model to penile carcinoma. Data from
the UK and the Netherlands show that the second-opinion network for penile cancer
could help to improve treatment standards and results in Germany. Current data
and the intended further development of the system are discussed.
PMID- 27488742
TI - Physiology in Perspective: The Body's Tubes Sustain Life but Underlie Disease.
PMID- 27488744
TI - Surgical quality of minimally invasive adrenalectomy for adrenocortical
carcinoma: a contemporary analysis using the National Cancer Database.
AB - OBJECTIVES: To compare quality outcomes between open (OA) and minimally invasive
(MIA) adrenalectomy for adrenocortical carcinoma (ACC). PATIENTS AND METHODS: In
the National Cancer Database, we identified 481 patients with non-metastatic ACC
who underwent adrenalectomy from 2010 to 2013. OA and MIA were compared on
positive surgical margin (PSM) and lymph node dissection (LND) rates (primary
outcomes), and lymph node yield, length of stay (LOS), readmission, and overall
survival (secondary outcomes). Using the intention-to-treat principle, minimally
invasive-converted-to-open cases were considered MIA. Logistic regression
analysis was used to identify predictors of PSMs and LND. Associations between
approach and the outcomes were further assessed by stage and tumour size.
RESULTS: Overall, 161 patients (33.5%) underwent MIA. MIA was used more commonly
in older, comorbid patients; for smaller, localised tumours; and at lower-volume
centres. In the intention-to-treat analysis, MIA independently predicted PSMs
[odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.6; P = 0.03) and no LND
(OR 0.1, 95% CI 0.03-0.6; P = 0.01). On subgroup analysis, the association
between MIA and PSMs only held true for pT3 disease (48.7% vs 26.7%, P = 0.01). A
higher PSM rate was seen for tumours of >=10 cm managed with MIA vs OA, but this
difference was not significant (28.2% vs 18.5%, P = 0.16). Likewise, the
association between MIA and no LND was only observed for male patients, tumours
>=10 cm, and cN0 disease. After excluding minimally-invasive-converted-to-open
cases, the difference in PSM was less pronounced and non-significant (OR 1.8, 95%
CI 0.9-3.4; P = 0.08). MIA was associated with significantly shorter median LOS
(3 vs 6 days, P < 0.01) and non-significantly decreased readmissions (4.4% vs
8.8%, P = 0.08) compared to OA without any difference in lymph node yield or
overall survival. CONCLUSION: For organ-confined disease, MIA offers comparable
surgical quality to OA, while expediting inpatient recovery. OA is associated
with superior outcomes for locally advanced disease.
PMID- 27488745
TI - Structure activity relationship study on the peptide hormone preptin, a novel
bone-anabolic agent for the treatment of osteoporosis.
AB - Preptin is a 34-residue pancreatic hormone shown to be anabolic to bone in vitro
and in vivo. The bone activity of preptin resides within the (1-16) N-terminal
fragment. Due to its peptidic nature, the truncated fragment of preptin is
enzymatically unstable; however it provides an attractive framework for the
creation of stable analogues using various peptidomimetic techniques. An alanine
scan of preptin (1-16) was undertaken which showed that substitution of Ser at
position 3 or Pro at position 14 did not inhibit the proliferative activity of
preptin in primary rat osteoblasts (bone-forming cells). Importantly, Ser-3 to
Ala substitution also showed a significant activity on osteoblast differentiation
in vitro and increased the formation of mineralised bone matrix. Additional
modifications with non-proteinogenic amino acids at position 3 improved the
stability in liver microsomes, but diminished the osteoblast proliferative
activity. In addition, to provide greater structural diversity, a series of
macrocyclic preptin (1-16) analogues was synthesised using head-to-tail and head
to-side chain macrolactamisation as well as ring-closing metathesis. However, a
detrimental effect on osteoblast activity was observed upon macrocyclisation.
PMID- 27488743
TI - Regulation of Gastrointestinal Smooth Muscle Function by Interstitial Cells.
AB - Interstitial cells of mesenchymal origin form gap junctions with smooth muscle
cells in visceral smooth muscles and provide important regulatory functions. In
gastrointestinal (GI) muscles, there are two distinct classes of interstitial
cells, c-Kit(+) interstitial cells of Cajal and PDGFRalpha(+) cells, that
regulate motility patterns. Loss of these cells may contribute to symptoms in GI
motility disorders.
PMID- 27488746
TI - Relationship between calculated total antioxidant status and atherosclerotic
coronary artery disease.
AB - OBJECTIVE: Antioxidants play a major role in the cellular protection cascade
against oxidative damage. Oxidative stress has been linked to the pathogenesis of
coronary atherosclerosis. Our aim was to evaluate the association between
calculated serum total antioxidant status (cTAS) and the presence and severity of
coronary artery disease (CAD). METHODS: One hundred and seventy-four patients
with angiographically documented significant (>=50%) luminal stenosis (n=123) or
with minimal (<50%) luminal stenosis (n=51) in at least one coronary artery or
major branch segment in the epicardial coronary tree were categorized as CAD+
group; 88 patients with no luminal stenosis were considered as the control group.
The level of cTAS (mmol/L) was evaluated using the following equation:
(0.63*albumin concentration)+(1.02*uric acid concentration)+(1.53*bilirubin
concentration). RESULTS: In univariate analyses, mean levels of cTAS, uric acid,
and creatinine were significantly higher in CAD+ group than in controls. However,
adjusted cTAS level was not found to be a CAD predictor in the total population
[odds ratio (OR)=1.20; 95% confidence interval (CI): 0.81-1.76; p=0.364] or in
men (OR=1.25; 95% CI: 0.73-2.12; p=0.420) and women (OR=1.20; 95% CI: 0.66-2.19;
p=0.553). A weak but statistically significant correlation was found between cTAS
and Gensini score (Spearman's rho=0.16, p=0.015). CONCLUSION: In patients with
suspicious CAD, the level of cTAS was not found to be an independent predictor
for the presence of CAD. Further studies with larger sample size are required to
confirm the results.
PMID- 27488747
TI - SYNTAX score predicts postoperative atrial fibrillation in patients undergoing on
pump isolated coronary artery bypass grafting surgery.
AB - OBJECTIVE: Atrial fibrillation (AF) is the most common arrhythmia following
coronary artery by-pass graft surgery (CABG). The value of SYNTAX score to
predict postoperative atrial fibrillation (PoAF) has not been clearly addressed.
We aimed to evaluate this relationship in patients undergoing isolated CABG.
METHODS: This study was designed as a single-center, non-randomized,
observational, prospective study. Ninety-four patients undergoing isolated on
pump CABG, who had sinus rhythm and were older than 18 years, were enrolled.
Demographic characteristics of the patients were recorded; SYNTAX score was
calculated preoperatively for each patient. The univariate and multivariate
logistic regression analysis were used to determine for predictors of PoAF.
RESULTS: The median SYNTAX score of the enrolled patients was 21, (56-5). PoAF
was observed in 31 (33.3%) patients. Univariate logistic regression showed that
age, chronic obstructive pulmonary disease (COPD), red blood cell distribution
width (RDW), urea, initial troponin I, peak postoperative troponin I,
interventricular septum, left atrial diameter, and SYNTAX score were
significantly associated with the frequency of PoAF following CABG. An
independent association was identified with age [beta: 0.088, p:0.023, OR: 1.092,
95% CI (1.012-1.179)], COPD [(beta: 2.222, p:0.003, OR: 9.228, 95% CI (2.150
39.602)], and SYNTAX score [(beta: 0.130, p:0.002, OR: 1.139, 95% CI (1.050
1.235)]. CONCLUSION: This study showed that a higher SYNTAX score was related to
more frequent PoAF in patients undergoing isolated on-pump CABG.
PMID- 27488748
TI - Relationship between the presence of left atrial thrombus in patients with mitral
stenosis and platelet-to-lymphocyte ratio.
AB - OBJECTIVE: Rheumatic carditis-induced mitral valve disease is associated with a
chronic inflammatory process. The close relationship between inflammation and
prothrombotic processes is known. Our goal was to examine the relationship
between the presence of left atrial (LA) thrombus in patients with rheumatic
mitral valve stenosis (RMVS) and platelet-to-lymphocyte ratio (PLR), which is an
inflammatory marker. METHODS: This cross-sectional study included 351 consecutive
patients diagnosed with RMVS upon presentation to the cardiology polyclinic. All
patients were evaluated using transthoracic and transesophageal echocardiography
and were divided into 2 groups: those with and without LA thrombus. In addition
to echocardiographic and biochemical parameters, PLR was compared between the
groups. Student's t-test, Mann-Whitney U test, logistic regression analysis, and
receiver operating characteristic (ROC) curve analysis were used for statistical
analysis. RESULTS: No significant differences in terms of age, gender, body mass
index, and comorbidities were found between the groups with and without LA
thrombus. In the group with LA thrombus, higher red cell distribution width, mean
platelet volume, and platelet count and lower lymphocyte count were detected. In
addition, C-reactive protein levels were significantly higher in the LA thrombus
group (4.7 vs. 2.7 mg/L, p<0.001). PLR was significantly higher in patients with
thrombus than in those without (133+/-38 vs. 119+/-31, p=0.001). Higher PLR was
identified as independently associated with the presence of LA thrombus (odds
ratio: 1.03, 95% confidence interval: 1-1.06, p=0.016). CONCLUSION: Higher PLR
was detected in the LA thrombus group of patients with RMVS.
PMID- 27488749
TI - Evaluation of heart rate recovery index in heavy smokers.
AB - OBJECTIVE: Cigarette smoking increases the risk of cardiovascular events. The
heart rate recovery index (HRRI) is an indicator of autonomous nervous system
function and is an independent prognostic risk factor for cardiovascular
diseases. In this study, we aimed to evaluate HRRI in heavy smokers. METHODS: A
total of 179 apparently healthy subjects (67 non-smokers as the control group and
112 heavy smokers) were enrolled into this prospective cross-sectional study. The
presence of hypertension, diabetes mellitus, and known cardiac or non-cardiac
diseases was specified as the exclusion criteria. Heavy cigarette smoking was
defined as the consumption of more than one packet of cigarette per day. All
subjects underwent the maximal Bruce treadmill test. HRRIs of the heavy cigarette
smoker group at 1, 2, 3, and 5 min after maximal exercise were calculated and
compared to those of the control group. Student t-test, chi-square test, and
analysis of covariance were used for statistical analysis. RESULTS: The baseline
characteristics of the two groups were similar, except for body mass index and
high-density lipoprotein level. HRRIs at 1, 2, 3, and 5 min after maximal
exercise were found to be significantly lower in the heavy smoker group (HRRI1:
26.78+/-8.81 vs. 32.82+/-10.34, p<0.001; HRRI2: 44.37+/-12.11 vs. 51.72+/-12.87,
p<0.001; HRRI3: 52.73+/-11.54 vs. 57.22+/-13.51, p=0.018; and HRRI5: 58.31+/
10.90 vs. 62.33+/-13.02, p=0.029). CONCLUSIONS: In the present study, we found
that HRRI was impaired in heavy smokers. Our results suggest that beside
previously known untoward effects on vascular biology, heavy smoking also has
deleterious effects on the neuro-cardiovascular system.
PMID- 27488750
TI - Feasibility and clinical benefit of cognitive-behavioral intervention for
preparing patients for transesophageal echocardiography.
AB - OBJECTIVE: Despite premedication, anxiety in patients undergoing transesophageal
echocardiography (TEE) is prevalent, often causing adverse physiological and
psychological effects and contributing to decreased patient compliance. We aimed
to evaluate the feasibility of cognitive-behavioral intervention (CBI) in
patients undergoing TEE and to assess its impact on the severity of anxiety,
patient's and physician's comfort, and administered dose of sedatives. METHODS:
Our study was designed as a prospective, single-center, single-blinded, case
controlled pilot study. The study group comprised 49 patients (26 men, 66+/-8
years old) referred for TEE. Before the examination, 26 randomly selected
patients underwent CBI. Sedatives were administered, if necessary. After the
examination, patient anxiety and patient's and physician's comfort were evaluated
using dedicated questionnaires and scores. Intergroup comparison was performed
using Student's t-test for independent variables and Mann-Whitney U test and
Pearson's chi-square test or Fisher's exact test for categorical variables.
RESULTS: The mean level of pre-TEE distress and anxiety were significantly lower
in patients receiving CBI than in those without intervention (p=0.022).
Furthermore, the application of CBI significantly reduced patient's discomfort
(p<0.001) and resulted in increased comfort of physician (p<0.001) during TEE.
The need of sedative administration (31% vs. 91%, p<0.001) and its mean dose was
significantly lower in patients receiving CBI (1.6+/-0.5 mg vs. 2.7+/-1.6 mg
midazolam, p=0.009). CONCLUSIONS: CBI is feasible in patients undergoing TEE. It
decreases patient's anxiety and discomfort and increases physician's comfort. It
also results in reduced use of sedatives during the examination.
PMID- 27488751
TI - Late deterioration of left ventricular function after right ventricular pacemaker
implantation.
AB - OBJECTIVES: Right ventricular (RV) pacing induces a left bundle branch block
pattern on ECG and may promote heart failure. Patients with dual chamber
pacemakers (DCPs) who present with progressive reduction in left ventricular
ejection fraction (LVEF) secondary to RV pacing are candidates for cardiac
resynchronization therapy (CRT). This study analyzes whether upgrading DCP to CRT
with the additional implantation of a left ventricular (LV) lead improves LV
function in patients with reduced LVEF following DCP implantation. METHODS:
Twenty-two patients (13 males) implanted with DCPs and a high RV pacing
percentage (>90%) were evaluated in term of new-onset heart failure symptoms. The
patients were enrolled in this retrospective single-center study after obvious
causes for a reduced LVEF were excluded with echocardiography and coronary
angiography. In all patients, DCPs were then upgraded to biventricular devices.
LVEF was analyzed with a two-sided t-test. QRS duration and brain natriuretic
peptide (BNP) levels were analyzed with the unpaired t-test. RESULTS: LVEF
declined after DCP implantation from 54+/-10% to 31+/-7%, and the mean QRS
duration was 161+/-20 ms during RV pacing. NT-pro BNP levels were elevated
(3365+/-11436 pmol/L). After upgrading to a biventricular device, a biventricular
pacing percentage of 98.1+/-2% was achieved. QRS duration decreased to 108+/-16
ms and 106+/-20 ms after 1 and 6 months, respectively. There was a significant
increase in LVEF to 38+/-8% and 41+/-11% and a decrease in NT-pro BNP levels to
3088+/-2326 pmol/L and 1860+/-1838 pmol/L at 1 and 6 months, respectively.
CONCLUSION: Upgrading to CRT may be beneficial in patients with DCPs and heart
failure induced by a high RV pacing percentage.
PMID- 27488752
TI - The rs6817105 polymorphism on chromosome 4q25 is associated with the risk of
atrial fibrillation in the Chinese Han population.
AB - OBJECTIVE: Previous genome-wide association studies (GWASs) have identified
rs6817105-a single nucleotide polymorphism (SNP) on chromosome 4q25-to be
associated with the risk of atrial fibrillation (AF) in a European-descent
population. We recently demonstrated this association in a large cohort of
Japanese ancestry. Our present study was designed to determine this association
in the Chinese Han population. METHODS: This case-control study included 597 AF
cases and 996 AF-free controls, and rs6817105 SNPs were genotyped using the
TaqMan allelic discrimination assay. Odds ratios (ORs) and 95% confidence
intervals (95%CIs) were calculated in logistic regression models. RESULTS: The
genotype distribution of rs6817105-CC was significantly more frequent in the AF
patients than in the controls (p=3.24*10-32). In our study, logistic regression
analysis showed a strong association between rs6817105 and the risk of AF
(additive model: OR=2.22, 95%CI=1.89-2.61, p=2.33*10-22; dominant model: OR=2.96,
95%CI: 2.16-4.07, p=2.03*10-11; recessive model: OR=2.83, 95%CI=2.27-3.54,
p=4.00*10-20). Stratification analyses showed a borderline statistical difference
between subgroups of age for the association of rs6817105 with AF risk (p=0.049).
However, further interactive analysis indicated no significant interaction
between genotype of rs6817105 and age (p=0.178). CONCLUSION: Our finding
suggested that SNP rs6817105 may be associated with a high significant risk of AF
in the Chinese Han population, although more replicative studies of larger sample
size are needed to confirm this finding.
PMID- 27488753
TI - AB0 blood types: impact on development of prosthetic mechanical valve thrombosis.
AB - OBJECTIVE: The non-O alleles of the ABO genotype have been associated with an
increased risk of thrombosis. We aimed to assess the association between blood
group status and prosthetic valve thrombosis. METHODS: The association between
AB0 blood group status and prosthetic valve thrombosis was assessed in this
retrospective study. Transesophageal echocardiography was performed in 149
patients with a diagnosis of prosthetic valve thrombosis and in 192 control
subjects. RESULTS: Non-0 blood group type (p<0.001), presence of NYHA class III
IV status (p<0.001), and central nervous system (p<0.001) and non-central nervous
system (p<0.001) emboli were significantly more prevalent in prosthetic valve
thrombosis patients than in the control subjects. The incidence of ineffective
anticoagulation was higher in patients with prosthetic valve thrombosis than in
controls (p<0.001), as was the presence of moderate to severe left atrial
spontaneous echo contrast (p<0.001). The non-0 blood prosthetic valve thrombosis
subgroup had a higher incidence of obstructive thrombi and central nervous system
thrombotic events than having 0 blood prosthetic valve thrombosis subgroup. Non-0
blood group, ineffective anticoagulation, left atrial spontaneous echo contrast,
and a poor NYHA functional capacity were identified to be the predictors of
prosthetic valve thrombosis. CONCLUSION: Our data demonstrate that patients with
non-0 compared with 0 blood groups have higher incidence of prosthetic valve
thrombosis and central nervous system embolism and similar rates of non-central
nervous system embolism at presentation compared with 0 blood group type. Thus,
non-O blood group may be a risk factor that may be prone to the development of
prosthetic valve thrombosis in patients with prosthetic heart valves.
PMID- 27488755
TI - Relation between serum sodium levels and clinical outcomes in Turkish patients
hospitalized for heart failure: a multi-center retrospective observational study.
AB - OBJECTIVE: The purpose of the study was to analyze the prevalence of hyponatremia
and related 1-year outcomes of patients hospitalized for decompensated heart
failure with reduced ejection fraction (HFrEF) in Turkish patients. METHODS: A
total of 500 hospitalized patients with HFrEF were consecutively included in a
retrospective study at 19 participating hospitals. Patients were categorized
according to their serum sodium levels (sNa) on admission day as normonatremic
(135-145 mEq/L) and hyponatremic (<135 mEq/L). One-year all-cause mortality, re
hospitalization rates, and the impact of the changes in sNa at the time of
discharge to clinical outcomes were examined. RESULTS: Hyponatremia was observed
in 29% of patients. Patients with hyponatremia had lower blood pressures,
creatinine clearance, and left ventricular ejection fraction and higher serum
creatinine and BUN levels on admission compared with those with normonatremia.
Hyponatremia was associated with higher 1-year all-cause mortality (14% vs. 2.6%,
p<0.001) and re-hospitalization rates (46.9% vs. 33.7%, p=0.005). After
adjustment for covariates, hyponatremia was independently associated with 1-year
all-cause mortality (adjusted HR, 4.762; 95% CI, 1.941-11.764; p=0.001). At
discharge, only 50.8% of hyponatremic patients were corrected to normonatremia
(>=135 mEq/L). Those with persistent hyponatremia had the highest all-cause
mortality (p<0.001). CONCLUSION: In this study, it is demonstrated that
hyponatremia is relatively common and is associated with increased 1-year all
cause mortality and re-hospitalization rates among Turkish patients hospitalized
with HFrEF. Approximately 50% of the patients with initial low sNa had persistent
hyponatremia at discharge, and these patients had the worst clinical outcomes.
PMID- 27488754
TI - Post-discharge heart failure monitoring program in Turkey: Hit-PoinT.
AB - OBJECTIVE: The aim of this study was to assess the efficacy and feasibility of an
enhanced heart failure (HF) education with a 6-month telephone follow- up program
in post-discharge ambulatory HF patients. METHODS: The Hit-Point trial was a
multicenter, randomized, controlled trial of enhanced HF education with a 6-month
telephone follow-up program (EHFP) vs routine care (RC) in patients with HF and
reduced ejection fraction. A total of 248 patients from 10 centers in various
geographical areas were randomized: 125 to EHFP and 123 to RC. Education included
information on adherence to treatment, symptom recognition, diet and fluid
intake, weight monitoring, activity and exercise training. Patients were
contacted by telephone after 1, 3, and 6 months. The primary study endpoint was
cardiovascular death. RESULTS: Although all-cause mortality didn't differ between
the EHFP and RC groups (p=NS), the percentage of cardiovascular deaths in the
EHFP group was significantly lower than in the RC group at the 6-month follow up
(5.6% vs. 8.9%, p=0.04). The median number of emergency room visits was one and
the median number of all cause hospitalizations and heart failure
hospitalizations were zero. Twenty-tree percent of the EHFP group and 35% of the
RC group had more than a median number of emergency room visits (p=0.05). There
was no significant difference regarding the median number of all-cause or heart
failure hospitalizations. At baseline, 60% of patients in EHFP and 61% in RC were
in NYHA Class III or IV, while at the 6-month follow up only 12% in EHFP and 32%
in RC were in NYHA Class III or IV (p=0.001). CONCLUSION: These results
demonstrate the potential clinical benefits of an enhanced HF education and
follow up program led by a cardiologist in reducing cardiovascular deaths and
number of emergency room visits with an improvement in functional capacity at 6
months in post-discharge ambulatory HF patients.
PMID- 27488756
TI - Investigation of the arterial stiffness and associated factors in patients with
familial Mediterranean fever.
AB - OBJECTIVE: Because of the ongoing and recurring inflammatory state in familial
Mediterranean fever (FMF), patients may experience a high risk of cardiovascular
events. Our aim was to investigate the arterial stiffness and associated factors
in patients with FMF. METHODS: Sixty-nine consecutive FMF patients (including 11
females) and 35 controls (including 5 females) were enrolled in the study. The
demographical, clinical, and laboratory data and genetic mutations of the
patients were recorded. In the study, FMF patients according to the Tel-Hashomer
criteria were included, whereas patients with other known inflammatory
rheumatologic disease, atherosclerotic cardiovascular disease, hypertension,
diabetes, those under the age of 18 years, or those refusing to participate in
the study were excluded. Arterial stiffness measurements were performed using the
TensioMed device (TensoMed Ltd, Budapest, Hungary). RESULTS: The patient and
control groups were similar in terms of the mean ages, BMIs, gender, systolic
blood pressures, and smoking. FMF patients had a higher pulse wave velocity (PWV)
(7.73+/-1.3 and 7.18+/-1.1 m/s; p=0.03) and lower brachial and aortic
augmentation indexes (-64.6+/-14.6% and -54.6+/-25.9%, p=0.041 and 4.9+/-7.4% and
14.0+/-11.5%, p=0.025, respectively) compared with the controls. Thirty-one (45%)
patients were in the "during-attack" state and had higher PWV (8.17+/-1.6 and
7.38+/-0.9 m/s; p=0.027) compared with the asymptomatic patients. PWV was
correlated to serum CRP, WBC, ESR, fibrinogen, and neutrophil/lymphocyte ratios
(r=0.666, 0.429, 0.441, 0.388, and 0.460, respectively). The genetic mutation and
predominant attack type had no effect on arterial stiffness. CONCLUSION: FMF
patients have increased arterial stiffness during attacks compared with
asymptomatic patients and controls. The impaired arterial stiffness is correlated
to the severity of the inflammatory state rather than to the attack type or
genetic mutations.
PMID- 27488757
TI - High blood pressure: An obscuring misnomer?
AB - High blood pressure (BP) has been identified as a major risk factor for
cardiovascular complications. Although two-way association between BP and
hypertensive complications makes hypertension a near-ideal biomarker, BP as "the
cause" for the complications of HT per se still needs more evidence. Another
entirely possible hemodynamic candidate for causing hypertensive cardiovascular
adverse events can be flow or its iterations, which might have escaped the
attention because of its perfect correlation with pressure and harder technical
measurement. In this article, we analyze the evidence in hand to compare flow-
and pressure-related phenomena to delineate which of the two is the dominant
mediator of complications related to hypertension and should be the target for
therapy. A "flow-" rather than a "pressure-" based factor, as the causative or
major driving mediator of common hypertensive complications, may change our
understanding of hypertension pathophysiology.
PMID- 27488758
TI - A hypertrophic and dilated cardiomyopathic sudden cardiac death case; de novo
mutations in TTN and SGCD genes.
PMID- 27488760
TI - Vascular risk in familial Mediterranean fever.
PMID- 27488759
TI - Long-term prognostic significance of pentraxin-3 in patients with acute
myocardial infarction: 5-year prospective cohort study.
AB - OBJECTIVE: A predictive role of serum Pentraxin 3 (PTX3) for short-term adverse
cardiovascular events including mortality in acute myocardial infarction (AMI)
was reported in recent studies. The aim of the study was to investigate long-term
prognostic significance of serum PTX3 in an AMI with 5-year follow-up period in
this study. METHODS: In this prospective study, 140 patients, who were admitted
to the emergency department between January 2011 and December 2011 with acute
chest pain and/or dyspnea and diagnosed with AMI and 60 healthy controls were
included. PTX3 levels were measured at admission by using an ELISA method. The
study group was divided into tertiles on the basis of admission PTX3 values: the
high-PTX3 group (>=4.27 ng/mL), the middle-PTX3 groups (4.27-1.63 ng/mL), and the
low-PTX3 group (<=1.63 ng/mL). RESULTS: PTX3 level was significantly more greatly
increased in the AMI group than in the controls (2.27+/-0.81 vs. 0.86+/-0.50
ng/mL, p<0.001). PTX3 level was found to be significantly positively correlated
with TIMI score (r=0.368, p=0.037), high sensitive C-reactive protein (hsCRP)
(r=0.452, p=0.024), pro-BNP (r=0.386, p=0.029), troponin I (r=0.417, p=<0.001),
and GRACE score (r=0.355, p=0.045), and negatively correlated with HDL
cholesterol (r=-0.203, p=0.016) and LVEF (r=-0.345, p=0.028). In multivariate
analysis, PTX3 (OR=1.12, 95% CI 1.04-1.20; p=0.001) was a significant independent
predictor of long-term cardiovascular mortality, after adjusting for other risk
factors. CONCLUSION: PTX3 is a novel biomarker that may help to identify high
risk individuals with AMI, who are potentially at risk of early major adverse
cardiovascular events including mortality in the long-term period.
PMID- 27488761
TI - Modified transesophageal echocardiography of the dissected thoracic aorta; a
novel diagnostic approach.
AB - BACKGROUND: Transesophageal echocardiography (TEE) is a key diagnostic modality
in patients with acute aortic dissection, yet its sensitivity is limited by a
"blind-spot" caused by air in the trachea. After placement of a fluid-filled
balloon in the trachea visualization of the thoracic aorta becomes possible. This
method, modified TEE, has been shown to be an accurate test for the diagnosis of
upper aortic atherosclerosis. In this study we discuss how we use modified TEE
for the diagnosis and management of patients with (suspected) acute aortic
dissection. NOVEL DIAGNOSTIC APPROACH OF THE DISSECTED AORTA: Modified TEE
provides the possibility to obtain a complete echocardiographic overview of the
thoracic aorta and its branching vessels with anatomical and functional
information. It is a bedside test, and can thus be applied in hemodynamic
instable patients who cannot undergo computed tomography. Visualization of the
aortic arch allows differentiation between Stanford type A and B dissections and
visualization of the proximal cerebral vessels enables a timely identification of
impaired cerebral perfusion. During surgery modified TEE can be applied to
identify the true lumen for cannulation, and to assure that the true lumen is
perfused. Also, the innominate- and carotid arteries can be assessed for
structural integrity and adequate perfusion during multiple phases of the
surgical repair. CONCLUSIONS: Modified TEE can reveal the "blind-spot" of
conventional TEE. In patients with (suspected) aortic dissection it is thus
possible to obtain a complete echocardiographic overview of the thoracic aorta
and its branches. This is of specific merit in hemodynamically unstable patients
who cannot undergo CT. Modified TEE can guide also guide the surgical management
and monitor perfusion of the cerebral arteries.
PMID- 27488762
TI - Role of dihydrofolate reductase in tetrahydrobiopterin biosynthesis and lipid
metabolism in the oleaginous fungus Mortierella alpina.
AB - Mortierella alpina is a well-known polyunsaturated fatty acid-producing
oleaginous fungus. Analysis of the Mort. alpina genome suggests that there is a
putative dihydrofolate reductase (DHFR) gene playing a role in the salvage
pathway of tetrahydrobiopterin (BH4), which has never been explored in fungi
before. DHFR is the sole source of tetrahydrofolate and plays a key role in
maintaining BH4 levels. Transcriptome data analysis revealed that DHFR was up
regulated by nitrogen exhaustion, when Mort. alpina starts to accumulate lipids.
Significant changes were found in the fatty acid profile in Mort. alpina grown on
medium containing DHFR inhibitors compared to Mort. alpina grown on medium
without inhibitors. To explore the role of DHFR in folate/BH4 metabolism and its
relationship to lipid biosynthesis, we expressed heterologously the gene encoding
DHFR from Mort. alpina in Escherichia coli and we purified the recombinant enzyme
to homogeneity. The enzymatic activity was investigated by liquid chromatography
and MS and VIS-UV spectroscopy. The kinetic parameters and the effects of
temperature, pH, metal ions and inhibitors on the activity of DHFR were also
investigated. The transcript level of cytosolic NADPH-producing gene involved in
folate metabolism is down-regulated by DHFR inhibitors, which highlights the
functional significance of DHFR in lipid biosynthesis. The relationship between
DHFR and lipid metabolism is thus of major importance, and folate metabolism may
be an alternative NADPH source in fatty acid synthesis. To our knowledge, this
study is the first to report the comprehensive characterization of a BH4salvage
pathway in a fungus.
PMID- 27488765
TI - Step aside, Olympics: here's the Cybathlon.
PMID- 27488764
TI - Nitrates for the prevention of cardiac morbidity and mortality in patients
undergoing non-cardiac surgery.
AB - BACKGROUND: Cardiac complications are not uncommon in patients undergoing non
cardiac surgery, especially in patients with coronary artery disease (CAD) or at
high risk of CAD. Perioperative cardiac complications can lead to mortality and
morbidity, as well as higher costs for patient care. Nitrates, which are among
the most commonly used cardiovascular drugs, perform the function of decreasing
cardiac preload while improving cardiac blood perfusion. Sometimes, nitrates are
administered to patients undergoing non-cardiac surgery to reduce the incidence
of cardiac complications, especially for patients with CAD. However, their
effects on patients' relevant outcomes remain controversial. OBJECTIVES: * To
assess effects of nitrates as compared with other interventions or placebo in
reducing cardiac risk (such as death caused by cardiac factors, angina pectoris,
acute myocardial infarction, acute heart failure and cardiac arrhythmia) in
patients undergoing non-cardiac surgery.* To identify the influence of different
routes and dosages of nitrates on patient outcomes. SEARCH METHODS: We searched
the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and
the Chinese BioMedical Database until June 2014. We also searched relevant
conference abstracts of important anaesthesiology or cardiology scientific
meetings, the database of ongoing trials and Google Scholar.We reran the search
in January 2016. We added three potential new studies of interest to the list of
'Studies awaiting classification' and will incorporate them into our formal
review findings for the review update. SELECTION CRITERIA: We included randomized
controlled trials (RCTs) comparing nitrates versus no treatment, placebo or other
pharmacological interventions in participants (15 years of age and older)
undergoing non-cardiac surgery under any type of anaesthesia. DATA COLLECTION AND
ANALYSIS: We used standard methodological procedures as expected by Cochrane. Two
review authors selected trials, extracted data from included studies and assessed
risk of bias. We resolved differences by discussion and, when necessary, sought
help and suggestions from a third review author. We used a random-effects model
for data analysis. MAIN RESULTS: We included 27 randomized controlled trials
(RCTs) (8244 participants analysed). Investigators reported 12 different
comparisons of three different nitrates (nitroglycerin, isosorbide dinitrate and
nicorandil) versus no treatment, placebo or other pharmacological interventions.
All participants were older than 15 years of age. More than half of the trials
used general anaesthesia. Surgical procedures in most trials were at low to
moderate risk for perioperative cardiac complications. Only two comparisons
including three studies reported the primary outcome - all-cause mortality up to
30 days post operation. Researchers reported other morbidity outcomes and adverse
events in a variable and heterogeneous way, resulting in limited available data
for inclusion in the meta-analysis. We determined that the overall methodological
quality of included studies was fair to low, in accordance with risk of bias in
most domains.In summary, we found no difference in the primary outcome - all
cause mortality up to 30 days post operation - when nitroglycerin was compared
with no treatment (one study, 60 participants, 0/30 vs 1/30; (risk ratio (RR)
0.33, 95% confidence interval (CI) 0.01 to 7.87, very low-quality evidence based
on GRADE criteria) or with placebo (two studies, 89 participants, 1/45 vs 0/44;
RR 2.81, 95% CI 0.12 to 63.83, very low-quality evidence). Regarding our
secondary outcomes, we noted no statistically significant differences in angina
pectoris, acute myocardial infarction, acute heart failure, cardiac arrhythmia or
cardiac arrest in any comparisons. In comparisons versus nitroglycerin, although
more events of cardiac ischaemia were observed in participants receiving no
treatment or placebo, we found no statistically significant differences in any
comparisons, except the comparison of nicorandil versus placebo. One study
revealed a potential dose-dependent protective effect of nicorandil for cardiac
ischaemia.Adverse events were reported in a heterogeneous way among the
comparisons. In general, more participants treated with nitrates had hypotension,
tachycardia and headache, but investigators reported no statistically significant
differences between groups in any comparisons. AUTHORS' CONCLUSIONS: This
systematic review suggests that nitroglycerin or isosorbide dinitrate is not
associated with improvement in mortality and cardiac complications among patients
undergoing non-cardiac surgery. Limited evidence suggests that nicorandil may
reduce the risk of cardiac ischaemia in participants undergoing non-cardiac
surgery. Additional studies are needed to consolidate the evidence.However, the
data included in many of the analyses in this review are sparse - that is,
adequate data are few - resulting in very low power to detect differences between
nitrates and comparators. Thus, a more objective conclusion would state that
available evidence is insufficient to show whether nitrates are associated with
improvement in mortality and cardiac complications among patients undergoing non
cardiac surgery.Over the past decade, no high-quality studies have focused on
association of cardiac mortality and morbidity with use of nitrates during non
cardiac surgery. This review underlines the need for well-designed trials in this
field.
PMID- 27488763
TI - Emergency Department Visits for Adverse Drug Reactions Involving Alcohol: United
States, 2005 to 2011.
AB - BACKGROUND: Alcohol consumption may interfere with absorption, distribution,
metabolism, and excretion of medications and increase risk of adverse drug
reactions (ADR). Studies report increasing prescription medication use over time,
with many U.S. drinkers using alcohol-interactive medication. This study
identified trends in incidence of U.S. emergency department (ED) visits for ADR
with alcohol involvement (ADR-A), compared characteristics and disposition
between ADR-A visits and ADR visits without alcohol involvement (ADR-NA), and
examined frequency of implicated medications in such visits for 2005 to 2011.
METHODS: ADR visits were identified through the Drug Abuse Warning Network, a
national surveillance system monitoring drug-related ED visits. Analysis
accounted for sampling design effects and sampling weights. Estimates are
presented for totals (ages 12+), age group, and/or sex. Trends were assessed by
joinpoint log-linear regression. Differences between ADR-A and ADR-NA visits were
compared using two-tailed Rao-Scott chi-square tests. RESULTS: From 2005 to 2011,
incidence of ADR-A visits increased for males and females ages 21 to 34 and
females ages 55+. An average of 25,303 ADR-A visits ages 12+ occurred annually.
Compared with ADR-NA visits, ADR-A visits were more likely to involve males,
patients ages 21 to 54, and 2+ implicated drugs. Alcohol involvement increased
odds of more serious outcomes from ADR visits. Central nervous system (CNS)
agents were the most common medications in ADR-A visits (59.1%), with nearly half
being analgesics (mainly opioid). About 13.8% of ADR-A visits involved
psychotherapeutic agents, including antidepressants. Besides CNS and
psychotherapeutic agents, ADR-A visits involved a higher percentage of
genitourinary-tract agents (mainly for impotence) than ADR-NA visits. Sex and age
variations were observed with certain implicated medications. CONCLUSIONS: ED
visits for alcohol-drug interactions can be prevented by avoiding alcohol when
taking alcohol-interactive medications. Our results underscore the need for
healthcare professionals to routinely ask patients about alcohol consumption and
warn of ADR risks before prescribing and dispensing alcohol-interactive
medications.
PMID- 27488766
TI - UK research assessment should boost support for principal investigators.
PMID- 27488778
TI - Troubled Japanese space agency seeks fresh start.
PMID- 27488767
TI - Donald Trump's appeal should be a call to arms.
PMID- 27488779
TI - Monumental proof to torment mathematicians for years to come.
PMID- 27488780
TI - Scientists seek influence on 'Brexit ministry'.
PMID- 27488782
TI - Corrections.
PMID- 27488781
TI - Legal confusion threatens to slow data science.
PMID- 27488783
TI - Scholarly Olympics: How the games have shaped research.
PMID- 27488784
TI - Welcome to the Cyborg Olympics.
PMID- 27488785
TI - Take responsibility for electronic-waste disposal.
PMID- 27488789
TI - Endocrine disruptors: Refereed science to guide action on EDCs.
PMID- 27488790
TI - China: Standardize R&D costing.
PMID- 27488791
TI - Health research: Mentoring female scientists in Africa.
PMID- 27488792
TI - China: Change tack to boost basic research.
PMID- 27488793
TI - Correction.
PMID- 27488794
TI - Atomic physics: A milestone in quantum computing.
PMID- 27488795
TI - Biomedical science: Protection for anaesthetized mice.
PMID- 27488796
TI - Quantum physics: Destruction of discrete charge.
PMID- 27488797
TI - Controlling charge quantization with quantum fluctuations.
AB - In 1909, Millikan showed that the charge of electrically isolated systems is
quantized in units of the elementary electron charge e. Today, the persistence of
charge quantization in small, weakly connected conductors allows for circuits in
which single electrons are manipulated, with applications in, for example,
metrology, detectors and thermometry. However, as the connection strength is
increased, the discreteness of charge is progressively reduced by quantum
fluctuations. Here we report the full quantum control and characterization of
charge quantization. By using semiconductor-based tunable elemental conduction
channels to connect a micrometre-scale metallic island to a circuit, we explore
the complete evolution of charge quantization while scanning the entire range of
connection strengths, from a very weak (tunnel) to a perfect (ballistic) contact.
We observe, when approaching the ballistic limit, that charge quantization is
destroyed by quantum fluctuations, and scales as the square root of the residual
probability for an electron to be reflected across the quantum channel; this
scaling also applies beyond the different regimes of connection strength
currently accessible to theory. At increased temperatures, the thermal
fluctuations result in an exponential suppression of charge quantization and in a
universal square-root scaling, valid for all connection strengths, in agreement
with expectations. Besides being pertinent for the improvement of single-electron
circuits and their applications, and for the metal-semiconductor hybrids relevant
to topological quantum computing, knowledge of the quantum laws of electricity
will be essential for the quantum engineering of future nanoelectronic devices.
PMID- 27488798
TI - Demonstration of a small programmable quantum computer with atomic qubits.
AB - Quantum computers can solve certain problems more efficiently than any possible
conventional computer. Small quantum algorithms have been demonstrated on
multiple quantum computing platforms, many specifically tailored in hardware to
implement a particular algorithm or execute a limited number of computational
paths. Here we demonstrate a five-qubit trapped-ion quantum computer that can be
programmed in software to implement arbitrary quantum algorithms by executing any
sequence of universal quantum logic gates. We compile algorithms into a fully
connected set of gate operations that are native to the hardware and have a mean
fidelity of 98 per cent. Reconfiguring these gate sequences provides the
flexibility to implement a variety of algorithms without altering the hardware.
As examples, we implement the Deutsch-Jozsa and Bernstein-Vazirani algorithms
with average success rates of 95 and 90 per cent, respectively. We also perform a
coherent quantum Fourier transform on five trapped-ion qubits for phase
estimation and period finding with average fidelities of 62 and 84 per cent,
respectively. This small quantum computer can be scaled to larger numbers of
qubits within a single register, and can be further expanded by connecting
several such modules through ion shuttling or photonic quantum channels.
PMID- 27488799
TI - Carbon-based tribofilms from lubricating oils.
AB - Moving mechanical interfaces are commonly lubricated and separated by a
combination of fluid films and solid 'tribofilms', which together ensure easy
slippage and long wear life. The efficacy of the fluid film is governed by the
viscosity of the base oil in the lubricant; the efficacy of the solid tribofilm,
which is produced as a result of sliding contact between moving parts, relies
upon the effectiveness of the lubricant's anti-wear additive (typically zinc
dialkyldithiophosphate). Minimizing friction and wear continues to be a
challenge, and recent efforts have focused on enhancing the anti-friction and
anti-wear properties of lubricants by incorporating inorganic nanoparticles and
ionic liquids. Here, we describe the in operando formation of carbon-based
tribofilms via dissociative extraction from base-oil molecules on catalytically
active, sliding nanometre-scale crystalline surfaces, enabling base oils to
provide not only the fluid but also the solid tribofilm. We study nanocrystalline
catalytic coatings composed of nitrides of either molybdenum or vanadium,
containing either copper or nickel catalysts, respectively. Structurally, the
resulting tribofilms are similar to diamond-like carbon. Ball-on-disk tests at
contact pressures of 1.3 gigapascals reveal that these tribofilms nearly
eliminate wear, and provide lower friction than tribofilms formed with zinc
dialkyldithiophosphate. Reactive and ab initio molecular-dynamics simulations
show that the catalytic action of the coatings facilitates dehydrogenation of
linear olefins in the lubricating oil and random scission of their carbon-carbon
backbones; the products recombine to nucleate and grow a compact, amorphous
lubricating tribofilm.
PMID- 27488800
TI - 'Kudos' promises to help scientists promote their papers to new audiences.
PMID- 27488802
TI - Do children, adolescents, and young adults with type 1 diabetes have increased
prevalence of sleep disorders?
AB - BACKGROUND: Sleep has been shown to impact glucose regulation, and may be altered
in persons with type 1 diabetes (T1D). OBJECTIVE: To assess sleep characteristics
in T1D patients and the possible association between sleep disturbances and
diabetes-related variables. SUBJECTS AND METHODS: In a cross-sectional study in
154 young patients with T1D and 154 age-range-matched nondiabetic controls
subjective sleep characteristics were assessed using validated questionnaires:
Sleep Disturbance Scale for Children (SDSC), Adolescent Sleep-Wake Scale (ASWS),
Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS). Clinical
and disease-related variables were obtained from medical charts. RESULTS: Sleep
disorders were frequent in all age groups, with no significant difference in
prevalence or total scores of the SDSC, ASWS, PSQI, or ESS between the patients
and the controls. In T1D children, SDSC score was significantly higher in those
using continuous glucose monitoring (CGM) vs glucose meters (P = .042). The score
of disorders related to "initiating and maintaining sleep" was significantly
higher in those treated with pumps vs patients treated with injections (P =
.014), in those using CGM vs glucose meters (P = .02), and in those with
nocturnal hypoglycemia vs those without (P = .023). The percentage of children
with excessive daytime sleepiness was significantly lower in patients vs controls
(P = .035). No significant differences were found in the other two age groups.
CONCLUSIONS/INTERPRETATION: The prevalence of sleep disorders among most of the
young T1D patients was no higher than in the nondiabetic population. Studies
using objective sleep measures are warranted to further assess sleep quality in
T1D patients.
PMID- 27488803
TI - A role for the spindle assembly checkpoint in the DNA damage response.
AB - Spontaneous DNA damage poses a continuous threat to genomic integrity. If
unchecked, genotoxic insults result in genomic instability, a hallmark of cancer
cells. In eukaryotic cells a DNA Damage Response (DDR) detects and responds to
genotoxic stress, acting as an anti-cancer barrier in humans. Among other
actions, the DDR blocks the segregation of incompletely replicated or damaged
chromosomes, thus preventing aneuploidy. In a work aimed at better understanding
such S-M control, we recently showed that cells block anaphase through different
control pathways. The S phase checkpoint kinase Mec1/ATR inhibits mitotic Cyclin
Dependent Kinase activity through effector kinases Swe1/Wee1 and Rad53/Chk2.
Cells also stabilize the levels of Pds1/securin to block sister chromatid
segregation in response to DNA damage. We show here that Pds1/securin abundance
is still secured when the S phase checkpoint response is fully abrogated in
mec1/ATR tel1/ATM double null mutants. When such cells are exposed to genotoxic
stress, Pds1/securin is stabilized in a spindle assembly checkpoint (SAC)
dependent manner. Disruption of the SAC and the S phase checkpoint together,
allows chromosome segregation in the presence of DNA damage or replication
stress. Our results place the SAC as a part of the DDR, which appears to count on
different, independent control layers to preserve genomic integrity when
chromosome replication is challenged.
PMID- 27488805
TI - First record of predation between Dasyatis species.
PMID- 27488804
TI - Plastid phylogenomic study of species within the genus Zea: rates and patterns of
three classes of microstructural changes.
AB - This project examines the relationships within the genus Zea using complete
plastid genomes (plastomes). While Zea mays has been well studied, congeneric
species have yet to be as thoroughly examined. For this study four complete
plastomes and a fifth nearly complete plastome were sequenced in the five species
(Zea diploperennis, Zea perennis, Zea luxurians, Zea nicaraguensis, and Zea mays
subsp. huehuetenangensis) by Sanger or next-generation methods. An analysis of
the microstructural changes, such as inversions, insertion or deletion mutations
(indels) and determination of their frequencies were performed for the complete
plastomes. It was determined that 193 indels and 15 inversions occurred across
the examined plastomes of Zea. Tandem repeat indels were the most common type of
microstructural change observed. Divergence times were estimated using a
noncorrelated relaxed clock method. Divergence dates for specific nodes relative
to Zea were calculated to fall between 38,000 years before present (YBP) for the
subspecies included in this study and 23,000 YBP for section Luxuriantes included
in this study. The stem lineage of all Zea species was calculated to have
diverged at 176,000 YBP. The calculated mutation rates for the genus fell within
the range of 1.7E-8 to 3.5E-8 microstructural changes per site per year. These
rates of change are not uniform, despite the close relationships of taxa in this
study. Phylogenomic analyses using full plastome alignments were also conducted
to compare tree topologies from different types of mutations. In most cases, the
previous work examining Zea mitochondrial and nuclear data was confirmed.
PMID- 27488806
TI - Ultrasensitive sandwich-type electrochemical immunosensor based on trimetallic
nanocomposite signal amplification strategy for the ultrasensitive detection of
CEA.
AB - A novel and ultrasensitive sandwich-type electrochemical immunosensor was
designed for the quantitative detection of carcino-embryonic antigen (CEA). This
immunosensor was developed by using the trimetallic NiAuPt nanoparticles on
graphene nanosheets (NGs) nanosheets (NiAuPt-NGs) as excellent labels and beta
cyclodextrin functionalized reduced graphene oxide nanosheets (CD-NGs) as the
platform. The CD-NGs with high specific surface area good biocompatibility and
the ideal dispersibility was used to capture the primary antibodies (Ab1)
efficiently. The trimetallic NiAuPt-NGs nanocomposites were used as the labels
for signal amplification, showing better electrocatalytic activity towards the
reduction of hydrogen peroxide (H2O2), which is much better than that the
monometallic Pt-NGs, bimetallic NiPt-NGs and AuPt-NGs due to the synergetic
effect presented in NiAuPt-NGs. The NiAuPt-NGs nanocomposites consist of tightly
coupled nanostructures of Au, Ni and Pt, which have neither an alloy nor a core
shell structure. Under the optimal conditions, a linear range from 0.001-100
ng/mL and a low detection limit of 0.27 pg/mL were obtained for CEA. The proposed
electrochemical sandwich-type immunosensor may have a promising application in
bioassay and it enriches the electrochemical immunoassays.
PMID- 27488807
TI - A comparison of immunohistochemical and molecular methods used for analyzing the
BRAF V600E gene mutation in malignant melanoma in Taiwan.
AB - AIMS: The BRAF V600 mutation has been shown to be clinically meaningful in terms
of both the prognosis and sensitivity of BRAF inhibitors in patients with
metastatic melanoma. Recently, a BRAF V600E mutation-specific antibody, VE1, was
generated for the detection of tumors bearing BRAF V600E mutations. To determine
the clinical value of immunohistochemical testing, we compared the prevalence of
mutant BRAF detected by VE1 with direct sequencing results. METHODS: Paraffin
embedded, formalin-fixed melanoma biopsies were analyzed for the BRAF mutation
status by immunohistochemistry with the VE1 antibody. Sanger sequencing was
applied to verify the immunohistochemical results. RESULTS: A total of 73
melanoma cases with tumor samples from primary lymph nodes and metastatic sites
were selected for this study. Direct sequencing demonstrated that 18 of 73 cases
(24.6%) harbored the BRAF V600 mutation: 17 with V600E and one with V600K. All 18
tumors shown to harbor the BRAF V600E/K mutations were VE1-positive. One
additional case was false-positive for VE1. The sensitivity and specificity of
VE1 was 100% (18/18) and 98% (54/55), respectively. The overall concordance
between the immunohistochemical method and direct sequencing was excellent
(98.6%). CONCLUSIONS: Our findings demonstrate that immunohistochemical analysis
using VE1 constitutes a highly sensitive test for the detection of BRAF mutations
and suggest that this cost-effective method is suitable as a rapid diagnostic
approach complementary to molecular testing.
PMID- 27488809
TI - Human rights in occupational therapy education: A step towards a more
occupationally just global society.
AB - BACKGROUND/AIM: Education on human rights will place occupational therapists in a
strong position to address societal inequities that limit occupational engagement
for many client groups. The imminent changes to the Minimum Standard for the
Education of Occupational Therapists engender efforts towards social change and
will require university-level human rights education. This education might
enhance the profession's influence on disadvantaging social structures in order
to effect social change. To contribute to the evidence base for social change
education in occupational therapy, this research aims to understand the
knowledge, skills, confidence and learning experiences of occupational therapy
students who completed a human rights course. METHODS: Final year occupational
therapy students responded to questionnaires which included listing human rights,
a human rights scale measuring knowledge and confidence for working towards human
rights, and open questions. Numbers of rights listed, knowledge scores and
confidence scores were calculated. Responses to the open questions were
thematically analysed. RESULTS: After completing a human rights course, students
had good knowledge and moderate confidence to work with human rights. Three
themes were identified including 'learning about human rights', 'learning about
structural, societal and global perspectives on occupational engagement' and
'learning how occupational therapists can work with groups, communities and
populations: becoming articulate and empowered'. CONCLUSIONS: Human rights
education fosters the development of occupational therapists who are skilled,
knowledgeable, confident and empowered to address occupational injustices,
according to these research findings. To develop a more occupationally just
global society, education that considers iniquitous social structures and human
rights is necessary.
PMID- 27488808
TI - Hypoxic Preconditioning Inhibits Hypoxia-induced Apoptosis of Cardiac Progenitor
Cells via the PI3K/Akt-DNMT1-p53 Pathway.
AB - Research has demonstrated that hypoxic preconditioning (HP) can enhance the
survival and proliferation of cardiac progenitor cells (CPCs); however, the
underlying mechanisms are not fully understood. Here, we report that HP of c-kit
(+) CPCs inhibits p53 via the PI3K/Akt-DNMT1 pathway. First, CPCs were isolated
from the hearts of C57BL/6 mice and further purified by magnetic-activated cell
sorting. Next, these cells were cultured under either normoxia (H0) or HP for 6
hours (H6) followed by oxygen-serum deprivation for 24 hours (24h). Flow
cytometric analysis and MTT assays revealed that hypoxia-preconditioned CPCs
exhibited an increased survival rate. Western blot and quantitative real-time PCR
assays showed that p53 was obviously inhibited, while DNMT1 and DNMT3beta were
both significantly up-regulated by HP. Bisulphite sequencing analysis indicated
that DNMT1 and DNMT3beta did not cause p53 promoter hypermethylation. A reporter
gene assay and chromatin immunoprecipitation analysis further demonstrated that
DNMT1 bound to the promoter locus of p53 in hypoxia-preconditioned CPCs.
Together, these observations suggest that HP of CPCs could lead to p53 inhibition
by up-regulating DNMT1 and DNMT3beta, which does not result in p53 promoter
hypermethylation, and that DNMT1 might directly repress p53, at least in part, by
binding to the p53 promoter locus.
PMID- 27488810
TI - A case series and a review of the literature on foreign modelling agent reaction:
an emerging problem.
AB - Foreign modelling agent reactions (FMAR) are the result of the injection of
unapproved high-viscosity fluids with the purpose of cosmetic body modelling. Its
consequences lead to ulceration, disfigurement and even death, and it has reached
epidemic proportions in several regions of the world. We describe a series of
patients treated for FMARs in a specialised wound care centre and a thorough
review of the literature. A retrospective chart review was performed from January
1999 to September 2015 of patients who had been injected with non-medical foreign
agents and who developed cutaneous ulceration needing treatment at the
dermatology wound care centre. This study involved 23 patients whose ages ranged
from 22 to 67 years with higher proportion of women and homosexual men. The most
commonly injected sites were the buttocks (38.5%), legs (18%), thighs (15.4%) and
breasts (11.8%). Mineral oil (39%) and other unknown substances (30.4%) were the
most commonly injected. The latency period ranged from 1 week to 17 years.
Complications included several skin changes such as sclerosis and ulceration as
well as systemic complications. FMAR is a severe syndrome that may lead to deadly
complications, and is still very common in Latin America.
PMID- 27488811
TI - An epitope-imprinted piezoelectric diagnostic tool for Neisseria meningitidis
detection.
AB - Neisseria meningitidis, a human-specific bacterial pathogen causes bacterial
meningitis by invading the meninges (outer lining) of central nervous system. It
is the polysaccharide present on the bacterial capsid that distinguishes various
serogroups of N. meningitidis and can be utilized as antigens to elicit immune
response. A computational approach identified candidate T-cell epitopes from
outer membrane proteins Por B of N. meningitidis (MC58): (273 KGLVDDADI282 in
loop VII and 170 GRHNSESYH179 in loop IV) present on the exposed surface of
immunogenic loops of class 3 outer membrane proteins allele of N. meningitidis.
One of them, KGLVDDADI is used here for designing a diagnostic tool via
molecularly imprinted piezoelectric sensor (molecularly imprinted polymer-quartz
crystal microbalance) for N. meningitidis strain MC58. Methacrylic acid, ethylene
glycol dimethacrylate and azoisobutyronitrile were used as functional monomer,
cross-linker and initiator, respectively. The epitope can be simultaneously bound
to methacrylic acid and fitted into the shape-selective cavities. On extraction
of epitope sequence from thus grafted polymeric film, shape-selective and
sensitive sites were generated on electrochemical quartz crystal microbalance
crystal, ie, known as epitope imprinted polymers. Imprinting was characterized by
atomic force microscopy images. The epitope-imprinted sensor was able to
selectively bind N. meningitidis proteins present in blood serum of patients
suffering from brain fever. Thus, fabricated sensor can be used as a diagnostic
tool for meningitis disease.
PMID- 27488812
TI - Skin protective effect of guava leaves against UV-induced melanogenesis via
inhibition of ORAI1 channel and tyrosinase activity.
AB - Ultraviolet (UV) irradiation is a major environmental factor affecting
photoageing, which is characterized by skin wrinkle formation and
hyperpigmentation. Although many factors are involved in the photoageing process,
UV irradiation is thought to play a major role in melanogenesis. Tyrosinase is
the key enzyme in melanin synthesis; therefore, many whitening agents target
tyrosinase through various mechanisms, such as direct interference of tyrosinase
catalytic activity or inhibition of tyrosinase mRNA expression. Furthermore, the
highly selective calcium channel ORAI1 has been shown to be associated with UV
induced melanogenesis. Thus, ORAI1 antagonists may have applications in the
prevention of melanogenesis. Here, we aimed to identify the antimelanogenesis
agents from methanolic extract of guava leaves (Psidium guajava) that can inhibit
tyrosinase and ORAI1 channel. The n-butanol (47.47%+/-7.503% inhibition at 10
MUg/mL) and hexane (57.88%+/-7.09% inhibition at 10 MUg/mL) fractions were found
to inhibit ORAI1 channel activity. In addition, both fractions showed effective
tyrosinase inhibitory activity (68.3%+/-0.50% and 56.9%+/-1.53% inhibition,
respectively). We also confirmed that the hexane fraction decreased the melanin
content induced by UVB irradiation and the ET-1-induced melanogenesis in murine
B16F10 melanoma cells. These results suggest that the leaves of P. guajava can be
used to protect against direct and indirect UV-induced melanogenesis.
PMID- 27488813
TI - Cadaver-Based Simulation Increases Resident Confidence, Initial Exposure to
Fundamental Techniques, and May Augment Operative Autonomy.
AB - OBJECTIVE: Surgical simulation is an important adjunct in surgical education. The
majority of operative procedures can be simplified to core components. This study
aimed to quantify a cadaver-based simulation course utility in improving exposure
to fundamental maneuvers, resident and attending confidence in trainee
capability, and if this led to earlier operative independence. DESIGN: A list of
fundamental surgical procedures was established by a faculty panel. Residents
were assigned to a group led by a chief resident. Residents performed skills on
cadavers appropriate for PGY level. A video-recorded examination where they
narrated and demonstrated a task independently was then graded by attendings
using standardized rubrics. Participants completed surveys regarding improvements
in knowledge and confidence. SETTING: The course was conducted at the Emory
University School of Medicine and the T3 Laboratories in Atlanta, GA.
PARTICIPANTS: A total of 133 residents and 41 attendings participated in the
course. 133 (100%) participating residents and 32 (78%) attendings completed
surveys. RESULTS: Resident confidence in completing the assigned skill
independently increased from 3 (2-3) to 4 (3-4), p < 0.01. Residents stated that
a median of 40% (interquartile range: 20%-60%) of procedures were performed for
the first time in the course, and the same number had been performed only in the
course. The percentage of skills attendings believed residents could perform
independently increased from 40% (40%-60%) to 60% (60%->80%), p < 0.04.
Attendings were more likely to grant autonomy in the operating room after this
exercise (4 [3-5]). CONCLUSIONS: A cadaveric skills course focused on fundamental
maneuvers with objective confirmation of success is a viable adjunct to clinical
operative experience. Residents were formally exposed to fundamental surgical
maneuvers earlier as a result of this course. This activity improved both
resident and attending confidence in trainee operative skill, resulting in
increased attending willingness to grant a higher level of autonomy in the
operating room.
PMID- 27488814
TI - Diffusion of Robotic Technology Into Urologic Practice has Led to Improved
Resident Physician Robotic Skills.
AB - OBJECTIVE: To investigate whether propagation of robotic technology into urologic
practice and training programs has improved baseline urology resident trainee
robotic skills. DESIGN: Questionnaires were completed by each urology resident
trainee participating in a training course and asked about access to robotic
simulation, robot experience, and console time. Baseline resident trainee scores
on the Mimic Robotic Simulator (Mimic Technologies, Inc., Seattle, WA) from 27
participants of 2012 course were compared with the 2015 scores of 34 trainees on
4 standard Mimic exercises using Wilcoxon rank-sum tests. p = 0.05 or less were
considered statistically significant. PARTICIPANTS AND SETTING: Totally, 34
resident trainees from 17 programs in the Southeast Section of the American
Urological Association participated in an annual 2-day robotic training course.
RESULTS: Overall score, economy of motion score, and time to complete exercise
were all significantly better in the 2015 trainee group compared with the 2012
trainee group (p < 0.001) for the Peg Board 1, Camera Targeting 2, and Energy
Dissection exercises. Overall scores for needle targeting improved between 2012
and 2015 (p = 0.04). Trainee access to a simulator was not associated with
overall score on any of the 4 exercises in the 2015 group. In the 2015 group,
actual robotic console time was associated with better overall scores in Camera
Targeting 2 (p = 0.02) and Peg Board 1 (p = 0.04). CONCLUSIONS: Baseline resident
trainee performance on basic robotic simulator exercises has improved over the
past 3 years irrespective of robotic simulator access or console time.
PMID- 27488815
TI - Editorial introduction.
PMID- 27488816
TI - Heterochromatin compaction is regulated by Suv4-20h1 to maintains skeletal muscle
stem cells quiescence.
AB - In this report, Boonsanay and colleagues describe a novel mechanism of
maintenance of skeletal muscle stem cells [also known as satellite cells (SCs)]
quiescence via the di-methyltransferase Suv4-20h1, regulator of heterochromatin
formation. Conditional ablation of Suv4-20h1 in SCs leads notably to the loss of
the histone modification H4K20me2 on the distal regulatory element of Myod
combined with a relocation of the Myod locus toward a central position in the
nucleus. This switch in nuclear compartment is correlated with decreased
facultative H3K27me3 associated heterochromatin, and an increase in spontaneously
activated MYOD-expressing SCs in homeostatic muscles. Consequently, Suv4-20h1
knock-out SCs demonstrate compromised stem cell potential, as they fail to
efficiently self-renew and replenish the SC pool upon muscle injury. Strikingly,
restoring MYOD expression alone rescues the levels of facultative chromatin and
reverses the loss-of-quiescence phenotype.
PMID- 27488817
TI - Extensive Lobular Carcinoma In Situ with Pagetoid Spread into Multiple Papillomas
of the Breast.
PMID- 27488818
TI - Transcriptome landscape of Synechococcus elongatus PCC 7942 for nitrogen
starvation responses using RNA-seq.
AB - The development of high-throughput technology using RNA-seq has allowed
understanding of cellular mechanisms and regulations of bacterial transcription.
In addition, transcriptome analysis with RNA-seq has been used to accelerate
strain improvement through systems metabolic engineering. Synechococcus elongatus
PCC 7942, a photosynthetic bacterium, has remarkable potential for biochemical
and biofuel production due to photoautotrophic cell growth and direct CO2
conversion. Here, we performed a transcriptome analysis of S. elongatus PCC 7942
using RNA-seq to understand the changes of cellular metabolism and regulation for
nitrogen starvation responses. As a result, differentially expressed genes (DEGs)
were identified and functionally categorized. With mapping onto metabolic
pathways, we probed transcriptional perturbation and regulation of carbon and
nitrogen metabolisms relating to nitrogen starvation responses. Experimental
evidence such as chlorophyll a and phycobilisome content and the measurement of
CO2 uptake rate validated the transcriptome analysis. The analysis suggests that
S. elongatus PCC 7942 reacts to nitrogen starvation by not only rearranging the
cellular transport capacity involved in carbon and nitrogen assimilation pathways
but also by reducing protein synthesis and photosynthesis activities.
PMID- 27488819
TI - Septic arthritis of the knee due to Raoultella ornithinolytica.
PMID- 27488820
TI - Pleural fluid adenosine deaminase/serum C-reactive protein ratio for the
differentiation of tuberculous and parapneumonic effusions with neutrophilic
predominance and high adenosine deaminase levels.
AB - PURPOSE: Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) are
usually distinguished by cellular predominance and pleural fluid adenosine
deaminase (ADA) levels. However, both diseases may occasionally show similar
neutrophilic predominance and high ADA levels. In such cases, the differential
diagnosis between TPE and PPE is challenging and has been rarely investigated.
METHODS: A retrospective study was conducted on TPE and PPE patients with
neutrophilic exudate and pleural fluid ADA levels >=40 U/L. Individual and
combined parameters of routine blood and pleural fluid tests were compared
between the two groups, and receiver operating characteristic (ROC) curves were
constructed for identifying TPE. RESULTS: Thirty-six TPE and 41 PPE patients were
included. White blood cell counts, serum C-reactive protein (S-CRP), and pleural
fluid pH, lactate dehydrogenase, and ADA levels showed significant difference
between the two groups (p < 0.001). Among multiple parameters, pleural fluid
ADA/S-CRP ratio, which best reflected different local and systemic
characteristics between TPE and PPE, provided the highest diagnostic accuracy
with an area under the ROC curve of 0.93. At a cutoff value of 5.62, ADA/S-CRP
ratio had a sensitivity of 89 %, specificity of 88 %, positive likelihood ratio
of 7.29, and negative likelihood ratio of 0.13 for identifying TPE. Additionally,
more than half of TPE patients had a ratio above 15.82, while none of PPE
patients showed such findings. CONCLUSIONS: Pleural fluid ADA/S-CRP ratio, as a
simple method using routine laboratory tests, may be helpful in discriminating
between TPE and PPE patients with neutrophilic predominance and ADA >=40 U/L.
PMID- 27488821
TI - Effects of Physical Exercise on the Intestinal Mucosa of Rats Submitted to a
Hypothalamic Obesity Condition.
AB - The small intestine plays a role in obesity as well as in satiation. However, the
effect of physical exercise on the morphology and function of the small intestine
during obesity has not been reported to date. This study aimed to evaluate the
effects of physical exercise on morphological aspects of the rat small intestine
during hypothalamic monosodium glutamate (MSG)-induced obesity. The rats were
divided into four groups: Sedentary (S), Monosodium Glutamate (MSG), Exercised
(E), and Exercised Monosodium Glutamate (EMSG). The MSG and EMSG groups received
a daily injection of monosodium glutamate (4 g/kg) during the 5 first days after
birth. The S and E groups were considered as control groups and received
injections of saline. At weaning, at 21 days after birth, the EMSG and E groups
were submitted to swimming practice 3 times a week until the 90th day, when all
groups were sacrificed and the parameters studied recorded. Exercise
significantly reduced fat deposits and the Lee Index in MSG-treated animals, and
also reduced the thickness of the intestinal wall, the number of goblet cells and
intestinal alkaline phosphatase activity. However, physical activity alone
increased the thickness and height of villi, and the depth of the crypts. In
conclusion, regular physical exercise may alter the morphology or/and functions
of the small intestine, reducing the prejudicial effects of hypothalamic obesity.
Anat Rec, 299:1389-1396, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27488822
TI - Self-Healing Hydrogels.
AB - Over the past few years, there has been a great deal of interest in the
development of hydrogel materials with tunable structural, mechanical, and
rheological properties, which exhibit rapid and autonomous self-healing and self
recovery for utilization in a broad range of applications, from soft robotics to
tissue engineering. However, self-healing hydrogels generally either possess
mechanically robust or rapid self-healing properties but not both. Hence, the
development of a mechanically robust hydrogel material with autonomous self
healing on the time scale of seconds is yet to be fully realized. Here, the
current advances in the development of autonomous self-healing hydrogels are
reviewed. Specifically, methods to test self-healing efficiencies and recoveries,
mechanisms of autonomous self-healing, and mechanically robust hydrogels are
presented. The trends indicate that hydrogels that self-heal better also achieve
self-healing faster, as compared to gels that only partially self-heal.
Recommendations to guide future development of self-healing hydrogels are offered
and the potential relevance of self-healing hydrogels to the exciting research
areas of 3D/4D printing, soft robotics, and assisted health technologies is
highlighted.
PMID- 27488823
TI - Does screening for and intervening with multiple health compromising behaviours
and mental health disorders amongst young people attending primary care improve
health outcomes? A systematic review.
AB - BACKGROUND: Adolescence and young adulthood are important developmental periods.
Screening for health compromising behaviours and mental health disorders during
routine primary care visits has the potential to assist clinicians to identify
areas of concern and provide appropriate interventions. The objective of this
systematic review is to investigate whether screening and subsequent
interventions for multiple health compromising behaviours and mental health
disorders in primary care settings improves the health outcomes of young people.
METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta
Analyses (PRISMA) guidelines, literature searches were conducted in Medline,
PsycINFO, Scopus and Cochrane Library databases (Prospero registration number
CRD42013005828) using search terms representing four thematic concepts: primary
care, young people, screening, and mental health and health compromising
behaviour. To be eligible for inclusion, studies had to: include a measure of
health outcome; include at least 75 % of participants aged under 25 years; use a
screening tool that assessed more than one health domain; and be conducted within
a primary care setting. Risk of bias was assessed using the Quality Rating Scale.
RESULTS: From 5051 articles identified, nine studies fulfilled the inclusion
criteria and were reviewed: two randomised controlled trials (RCTs), one pilot
RCT, two clustered RCTs, one randomised study with multiple intervention groups
and no control group, one cluster RCT with two active arms, one longitudinal
study and one pre-post study. Seven studies, including two RCTs and one clustered
RCT, found positive changes in substance use, diet, sexual health or risky sexual
behaviour, alcohol-related risky behaviour, social stress, stress management,
helmet use, sleep and exercise. Of only two studies reporting on harms, one
reported a negative health outcome of increased alcohol use. CONCLUSIONS: There
is some evidence that the use of screening and intervention with young people for
mental health disorder or health compromising behaviours in clinical settings
improves health outcomes. Along with other evidence that young people value
discussions of health risks with their providers, these discussions should be
part of the routine primary care of young people. Further quality studies are
needed to strengthen this evidence.
PMID- 27488824
TI - Dulaglutide in the treatment of adult type 2 diabetes: a perspective for primary
care providers.
AB - Approximately 90% of T2D patients in the US are diagnosed and treated in the
primary care setting, and the majority of the burden of disease management falls
to primary care providers. Here, we discuss the clinical data for once weekly
dulaglutide, e.g. the results of seven completed Phase 3 trials, patient
preference studies, patient reported outcomes (PRO), and clinical data
surrounding the dulaglutide administration device. Dulaglutide 1.5 mg once weekly
demonstrated superiority to placebo, metformin, sitagliptin, exenatide BID, and
insulin glargine (in 2 trials), and non-inferiority to liraglutide in reduction
of HbA1c from baseline, with an acceptable safety profile. Dulaglutide-treated
patients achieved the composite endpoint of an HbA1c <7.0% with no hypoglycemia,
no severe hypoglycemia, and no weight gain significantly more than metformin,
sitagliptin, exenatide BID or insulin glargine treated patients. Dulaglutide
consistently showed an early onset of glycemic control, lasting up to 104 weeks.
Additionally, PRO and patient preference data support the benefit of once weekly
dulaglutide for the treatment of T2D.
PMID- 27488825
TI - US officials issue travel alert for Miami area as Zika cases rise to 15.
PMID- 27488826
TI - Safety Assessment of Hydroxypropyl Bis(N-Hydroxyethyl-p-Phenylenediamine) HCl as
Used in Cosmetics.
AB - The Cosmetic Ingredient Review Expert Panel (CIR Panel) reviewed the safety of
hydroxypropyl bis(N-Hydroxyethyl-p-Phenylenediamine) HCl, which functions as an
oxidative hair dye ingredient. The Panel considered relevant animal and human
data provided in this safety assessment and concluded that hydroxypropyl bis(N
hydroxyethyl-p-phenylenediamine) HCl is safe for use in oxidative hair dye
formulations as described in this safety assessment.
PMID- 27488827
TI - The natural history of cutaneous propionibacteria, and reclassification of
selected species within the genus Propionibacterium to the proposed novel genera
Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and
Pseudopropionibacterium gen. nov.
AB - The genus Propionibacterium in the family Propionibacteriaceaeconsists of species
of various habitats, including mature cheese, cattle rumen and human skin.
Traditionally, these species have been grouped as either classical or cutaneous
propionibacteria based on characteristic phenotypes and source of isolation. To
re-evaluate the taxonomy of the family and to elucidate the interspecies
relatedness we compared 162 public whole-genome sequences of strains representing
species of the family Propionibacteriaceae. We found substantial discrepancies
between the phylogenetic signals of 16S rRNA gene sequence analysis and our high
resolution core-genome analysis. To accommodate these discrepancies, and to
address the long-standing issue of the taxonomically problematic
Propionibacterium propionicum, we propose three novel genera,
Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and
Pseudopropionibacterium gen. nov., and an amended description of the genus
Propionibacterium. Furthermore, our genome-based analyses support the amounting
evidence that the subdivision of Propionibacterium freudenreichii into subspecies
is not warranted. Our proposals are supported by phylogenetic analyses, DNA G+C
content, peptidoglycan composition and patterns of the gene losses and
acquisitions in the cutaneous propionibacteria during their adaptation to the
human host.
PMID- 27488830
TI - Indirect Calorimetry in Mechanically Ventilated Patients: A Prospective,
Randomized, Clinical Validation of 2 Devices Against a Gold Standard.
AB - BACKGROUND AND AIMS: The 2 currently available indirect calorimeters, CCM Express
Indirect Calorimeter (MedGraphics, St Paul, MN) and Quark RMR ICU Indirect
Calorimeter (COSMED, Rome, Italy), have not been validated against a gold
standard in mechanically ventilated patients. Our aim was to do so using a gold
standard, modified Tissot bell-spirometer method in mechanically ventilated
patients who were hemodynamically, respiratory, and metabolically stable.
METHODS: We studied 30 patients undergoing general anesthesia and major
gynecological surgery. We measured oxygen consumption ([Formula: see text]O2) and
resting energy expenditure (REE) in a randomized, sequential, crossover design
with double determination of each device. RESULTS: Compared with the modified
Tissot bell-spirometer, the CCM Express Indirect Calorimeter demonstrated a mean
Delta-REE of +361 kcal/d, corresponding to a 31% overestimation of energy
requirements. Bland-Altman analysis for REE showed a mean (SD) bias of 384 (124)
with limits of agreement 142-627 kcal/d. QUARK RMR ICU demonstrated a mean Delta
REE of 81 kcal/d, corresponding to a 7% overestimation of energy requirements.
Bland-Altman plot analysis showed a mean (SD) bias of 77 (167) with limits of
agreement -249 to 404 kcal/d. CONCLUSIONS: The QUARK RMR ICU Indirect Calorimeter
compared better with the gold standard for values of [Formula: see text]O2 and
REE than did the CCM Express Indirect Calorimeter in mechanically ventilated
patients who were circulatory and respiratory stable. Both indirect calorimeters
had low precision.
PMID- 27488829
TI - Development and Validation of a Method for Alcohol Analysis in Brain Tissue by
Headspace Gas Chromatography with Flame Ionization Detector.
AB - Ethanol is the most widely used and abused drug. While blood is the preferred
specimen for analysis, tissue specimens such as brain serve as alternative
specimens for alcohol analysis in post-mortem cases where blood is unavailable or
contaminated. A method was developed using headspace gas chromatography with
flame ionization detection (HS-GC-FID) for the detection and quantification of
ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens.
Unfixed volatile-free brain tissue specimens were obtained from the Department of
Pathology at Virginia Commonwealth University. Calibrators and controls were
prepared from 4-fold diluted homogenates of these brain tissue specimens, and
were analyzed using t-butanol as the internal standard. The chromatographic
separation was performed with a Restek BAC2 column. A linear calibration was
generated for all analytes (mean r2 > 0.9992) with the limits of detection and
quantification of 100-110 mg/kg. Matrix effect from the brain tissue was
determined by comparing the slopes of matrix prepared calibration curves with
those of aqueous calibration curves; no significant differences were observed for
ethanol, acetone, isopropanol, methanol and n-propanol. The bias and the CVs for
all volatile controls were <=10%. The method was also evaluated for carryover,
selectivity, interferences, bench-top stability and freeze-thaw stability. The HS
GC-FID method was determined to be reliable and robust for the analysis of
ethanol, acetone, isopropanol, methanol and n-propanol concentrations in brain
tissue, effectively expanding the specimen options for post-mortem alcohol
analysis.
PMID- 27488828
TI - Marked changes in dendritic structure and spine density precede significant
neuronal death in vulnerable cortical pyramidal neuron populations in the
SOD1(G93A) mouse model of amyotrophic lateral sclerosis.
AB - Amyotrophic lateral sclerosis (ALS) is characterised by the death of upper
(corticospinal) and lower motor neurons (MNs) with progressive muscle weakness.
This incurable disease is clinically heterogeneous and its aetiology remains
unknown. Increased excitability of corticospinal MNs has been observed prior to
symptoms in human and rodent studies. Increased excitability has been correlated
with structural changes in neuronal dendritic arbors and spines for decades.
Here, using a modified Golgi-Cox staining method, we have made the first
longitudinal study examining the dendrites of pyramidal neurons from the motor
cortex, medial pre-frontal cortex, somatosensory cortex and entorhinal cortex of
hSOD1(G93A) (SOD1) mice compared to wild-type (WT) littermate controls at
postnatal (P) days 8-15, 28-35, 65-75 and 120. Progressive decreases in dendritic
length and spine density commencing at pre-symptomatic ages (P8-15 or P28-35)
were observed in layer V pyramidal neurons within the motor cortex and medial pre
frontal cortex of SOD1 mice compared to WT mice. Spine loss without concurrent
dendritic pathology was present in the pyramidal neurons of the somatosensory
cortex from disease-onset (P65-75). Our results from the SOD1 model suggest that
dendritic and dendritic spine changes foreshadow and underpin the neuromotor
phenotypes present in ALS and may contribute to the varied cognitive, executive
function and extra-motor symptoms commonly seen in ALS patients. Determining if
these phenomena are compensatory or maladaptive may help explain differential
susceptibility of neurons to degeneration in ALS.
PMID- 27488831
TI - Mass production of shaped particles through vortex ring freezing.
AB - A vortex ring is a torus-shaped fluidic vortex. During its formation, the fluid
experiences a rich variety of intriguing geometrical intermediates from spherical
to toroidal. Here we show that these constantly changing intermediates can be
'frozen' at controlled time points into particles with various unusual and
unprecedented shapes. These novel vortex ring-derived particles, are mass
produced by employing a simple and inexpensive electrospraying technique, with
their sizes well controlled from hundreds of microns to millimetres. Guided
further by theoretical analyses and a laminar multiphase fluid flow simulation,
we show that this freezing approach is applicable to a broad range of materials
from organic polysaccharides to inorganic nanoparticles. We demonstrate the
unique advantages of these vortex ring-derived particles in several applications
including cell encapsulation, three-dimensional cell culture, and cell-free
protein production. Moreover, compartmentalization and ordered-structures
composed of these novel particles are all achieved, creating opportunities to
engineer more sophisticated hierarchical materials.
PMID- 27488832
TI - Ultrasound-guided percutaneous lavage of calcific bursitis of the medial
collateral ligament of the knee: a case report and review of the literature.
AB - OBJECTIVES: Calcification of the medial collateral ligament (MCL) of the knee is
rare. The literature reports no positive outcomes when conservative treatment has
been followed. This paper reports a case of such calcification and its treatment
using ultrasound-guided percutaneous lavage (UGPL). METHODS: A 66-year-old
patient presented with medial knee pain. X-ray, ultrasound, and magnetic
resonance (MR) examinations revealed calcific bursitis of the MCL, which was
treated by UGPL. RESULTS: One month after treatment the patient was asymptomatic.
X-ray, ultrasound, and MR examinations confirmed the almost complete
disappearance of the calcification; only very tiny fragments remained.
CONCLUSIONS: Calcific bursitis of the MCL of the knee is very uncommon, but
should be taken into account in differential diagnoses for medial knee pain. UGPL
is proposed as a treatment for this condition.
PMID- 27488833
TI - Comparison of MRI and PET-CT in detecting the loco-regional recurrence of soft
tissue sarcomas during surveillance.
AB - OBJECTIVE: To investigate the diagnostic performance of MRI and PET-CT for the
detection of loco-regional recurrences after soft tissue sarcoma (STS) excision.
MATERIALS AND METHODS: From Dec 2003 to Aug 2014, 394 patients with STSs, who
were included in the electronic patient registry for initial or repeated surgery
at our hospital, were retrospectively reviewed. We identified 152 patients who
underwent regular postoperative follow-ups with both MRI and PET-CT, obtained
within a 3 month period of each other. We analyzed differences in the performance
of MRI and PET-CT for the diagnosis of loco-regional recurrences using McNemar's
test. The receiver-operating characteristic curves and calculations of the area
under the curve were used. RESULTS: Twenty patients were found to have a loco
regional recurrence after tumor excision. For MRI and PET-CT, the sensitivities
were 90.0 and 95.0 %, and the specificities 97.7 and 95.5 %, respectively, with
positive predictive values of 85.7 and 76.0 % and negative predictive values of
98.5 and 99.2 %, respectively. No significant difference was detected between the
sensitivities of MRI and PET-CT (p = 0.125). The area under the receiver
operating characteristic curve for PET-CT (0.952) was not significantly greater
than that for MRI (0.939; p = 0.6). CONCLUSION: MRI of the area of interest is
recommended for evaluation of tumor recurrence after surgical excision of STS.
PET-CT was shown to be effective for detection of STS recurrence, and comparable
to MRI. However, if PET-CT or MRI findings are inconclusive, the other modality
may be helpful in differentiating tumor recurrence from post-therapeutic tissue
change.
PMID- 27488834
TI - Casein kinase 1alpha has a non-redundant and dominant role within the CK1 family
in melanoma progression.
AB - BACKGROUND: We previously identified CK1alpha as a novel tumor suppressor in
melanoma and reported that the loss of CK1alpha leads to increased proliferation
and invasive growth of melanoma cells by strong activation of the Wnt/beta
catenin signaling pathway. METHODS: In this study we analyzed expression and the
functional effects of the dominantly expressed CK1- isoforms alpha, delta and
epsilon in melanoma cells by quantitative real-time PCR, western blot and
immunohistochemistry. We down-regulated CK1 kinase activity with isoform specific
siRNAs and small molecule inhibitors. Vice versa we overexpressed the CK1
isoforms alpha, delta and epsilon using viral vectors and tested the biological
effects on melanoma cell proliferation, migration and invasion. RESULTS: We show
that protein expression of all three CK1-isoforms is downregulated in metastatic
melanoma cells compared to benign melanocytic cells. Furthermore, the CK1delta
and epsilon isoforms are able to negatively regulate expression of each other,
whereas CK1alpha expression is independently regulated in melanoma cells.
Inhibition of the expression and activity of CK1delta or CK1epsilon by specific
inhibitors or siRNAs had no significant effect on the growth and survival of
metastatic melanoma cells. Moreover, the over-expression of CK1delta or
CK1epsilon in melanoma cells failed to induce cell death and cell cycle arrest
although p53 signaling was activated. This is in contrast to the effects of
CK1alpha where up-regulated expression induces cell death and apoptosis in
metastatic melanoma cells. CONCLUSION: These data indicate that CK1alpha has a
dominant and non-redundant function in melanoma cells and that the CK1delta and
epsilon isoforms are not substantially involved in melanoma progression.
PMID- 27488835
TI - Family Qualities, Self-Deprecation, and Depressive Symptoms of Zoroastrian Young
Adults in Immigrant Families.
AB - The aim of this study was to examine family qualities and self-deprecation in
relation to depressive symptoms of young adult Zoroastrians from immigrant
families in North America. Using snowball sampling and online surveys, self
report data were collected from 171 Zoroastrian young adults (i.e., 18-30 years
old) about their perception of cohesion in their families, conflict with their
parents, and the extent that they met parental general expectations (e.g., not
embarrassing the family). The findings from a path analysis showed that parent
child conflict and meeting parental expectations were indirectly related to
depressive symptoms through self-deprecation. Also, higher family cohesion
predicted lower levels of depressive symptoms among Zoroastrian young adults.
These results are similar to findings in studies with non Zoroastrians. The
results suggested prevention and interventions to decrease depressive symptoms
could target self-deprecating thoughts as well as perceived family dynamics.
PMID- 27488836
TI - Blood fatty acid patterns are associated with prostate cancer risk in a
prospective nested case-control study.
AB - BACKGROUND: Circulating fatty acids are highly correlated with each other, and
analyzing fatty acid patterns could better capture their interactions and their
relation to prostate cancer. We aimed to assess the associations between data
derived blood fatty acid patterns and prostate cancer risk. METHODS: We conducted
a nested case-control study in the Physicians' Health Study. Fatty acids levels
were measured in whole blood samples of 476 cases and their matched controls by
age and smoking status. Fatty acid patterns were identified using principal
component analysis. Conditional logistic regression was used to estimate odds
ratio (OR) and 95 % confidence interval (CI). RESULTS: Two patterns explaining
40.9 % of total variation in blood fatty acid levels were identified. Pattern 1,
which mainly reflects polyunsaturated fatty acid metabolism, was suggestively
positively related to prostate cancer risk (ORquintile 5 vs. quintile 1 = 1.37,
95 % CI = 0.91-2.05, P trend = 0.07). Pattern 2, which largely reflects de novo
lipogenesis, was significantly associated with higher prostate cancer risk
(ORquintile5 vs. quintile1 = 1.63, 95 % CI = 1.04-2.55, P trend = 0.02). This
association was similar across tumor stage, grade, clinical aggressiveness
categories and follow-up time. CONCLUSION: The two patterns of fatty acids we
identified were consistent with known interactions between fatty acid intake and
metabolism. A pattern suggestive of higher activity in the de novo lipogenesis
pathway was related to higher risk of prostate cancer.
PMID- 27488837
TI - A safe-repositioning maneuver for the management of benign paroxysmal positional
vertigo: Gans vs. Epley maneuver; a randomized comparative clinical trial.
AB - Benign paroxysmal positional vertigo (BPPV) is the most common cause of
peripheral vertigo. Some repositioning maneuvers have been described for its
management. The aim of this study was comparing the therapeutic effect of Epley
and Gans maneuvers in BPPV. This randomized clinical trial was performed from
September to December 2015. 73 patients with true vertigo diagnosed as BPPV
enrolled the study. They randomly assigned in quadripartite blocks to modified
Epley maneuver group (E) or Gans maneuver group (G). 1 day and 1 week after
intervention, the objective and subjective responses to treatment were assessed.
Statistical analysis was performed using the Chi-square test and regression model
in the SPSS software version 21. Thirty patients enrolled each group with a mean
age of 46.9 +/- 13.4 (E group) and 46.7 +/- 7.5 year (G group). 23.3 % of E group
and 26.7 % of G group were men (p = 0.766). In E and G groups in the first day,
subjective outcomes revealed 86.7 and 60 % rate of success (p = 0.02); and 86.7
and 56.7 % of patients exhibited objective improvement, respectively (p = 0.01).
After 1 week, the subjective and objective outcomes revealed improvement among 70
% of E group and 46.7 % of G group (p = 0.067). The only complication with
significant difference was cervical pain with a higher rate in E group (23.3 vs.
0.0 %, p = 0.005). These results revealed the similar long-term efficacy of Epley
and Gans maneuver for the treatment of BPPV. Cervical pain was most frequent
complication of Epley maneuver.
PMID- 27488838
TI - Effects of aging on the relationship between cognitive demand and step
variability during dual-task walking.
AB - A U-shaped relationship between cognitive demand and gait control may exist in
dual-task situations, reflecting opposing effects of external focus of attention
and attentional resource competition. The purpose of the study was twofold: to
examine whether gait control, as evaluated from step-to-step variability, is
related to cognitive task difficulty in a U-shaped manner and to determine
whether age modifies this relationship. Young and older adults walked on a
treadmill without attentional requirement and while performing a dichotic
listening task under three attention conditions: non-forced (NF), forced-right
(FR), and forced-left (FL). The conditions increased in their attentional demand
and requirement for inhibitory control. Gait control was evaluated by the
variability of step parameters related to balance control (step width) and
rhythmic stepping pattern (step length and step time). A U-shaped relationship
was found for step width variability in both young and older adults and for step
time variability in older adults only. Cognitive performance during dual tasking
was maintained in both young and older adults. The U-shaped relationship, which
presumably results from a trade-off between an external focus of attention and
competition for attentional resources, implies that higher-level cognitive
processes are involved in walking in young and older adults. Specifically, while
these processes are initially involved only in the control of (lateral) balance
during gait, they become necessary for the control of (fore-aft) rhythmic
stepping pattern in older adults, suggesting that attentional resources turn out
to be needed in all facets of walking with aging. Finally, despite the cognitive
resources required by walking, both young and older adults spontaneously adopted
a "posture second" strategy, prioritizing the cognitive task over the gait task.
PMID- 27488839
TI - The predictive value of early acute kidney injury for long-term survival and
quality of life of critically ill patients.
AB - BACKGROUND: Prognostic factors for the combination of long-term survival and
health-related quality of life (HRQoL) after intensive care unit (ICU) stay have
not yet been studied. Our aim was to assess whether early acute kidney injury
(eAKI), AKI occurring on the first day of ICU admission, is an independent
predictor of this combined one-year outcome. METHODS: We included all patients
admitted to the mixed ICU of the University Medical Centre Utrecht between July
2009 and April 2013, excluding patients with chronic dialysis, cardiac surgery,
and length of stay shorter than 24 hours. eAKI was defined using the risk,
injury, failure, loss, end-stage renal failure (RIFLE) classification, using a
newly developed algorithm to classify AKI based on routinely collected patient
data. In one-year survivors, HRQoL was measured using the EuroQoL 5D-3LTM (EQ-5D)
questionnaire. The primary outcome measure was "poor outcome", defined as an EQ
5D index score <0.4 or death after one year follow up. A multivariable Poisson
regression model was performed to adjust for age, comorbidities, admission type
and severity of disease factors. RESULTS: We enrolled 2,420 patients, of whom 871
(36.0 %) died within one year. An additional 286 of 1549 one-year survivors (11.8
%) experienced low HRQoL. The respective incidence of the RIFLE classes, risk,
injury and failure, were 456 (18.8 %), 253 (10.5 %) and 123 (5.1 %). After
adjustment for other covariates, the RIFLE classes, injury and failure, were
independently associated with poor outcome (adjusted relative risk 1.14, 95 % CI
1.01, 1.29; p = 0.03, and 1.25, 95 % CI 1.01, 1.55; p = 0.04), when compared to
no eAKI patients . The constituents of this composite outcome were also analysed
separately. In a Cox regression model the RIFLE classes, injury and failure, were
significantly associated with mortality (adjusted hazard ratio 1.35, 95 % CI
1.11, 1.65; p <0.01, and 1.78, 95 % CI 1.38, 2.30; p <0.01). In one-year
survivors specifically, none of the RIFLE classes were significantly associated
with low HRQoL. CONCLUSIONS: ICU patients with moderate or severe AKI during the
first 24 hours have a higher probability of mortality or low HRQoL (combined poor
outcome), one year after ICU admission. Together with other available early
prognostic factors, information on early acute kidney injury could improve
informed decision-making on the continuation or withdrawal of treatment in ICU
patients.
PMID- 27488840
TI - Engaging diverse populations in biospecimen donation: results from the Hoy y
Manana study.
AB - The disproportionately lower number of certain subpopulations participating in
clinical and prevention research has a significant impact on the
representativeness of scientific outcomes. The Hoy y Manana program (Today and
Tomorrow) was developed as a culturally and linguistically appropriate education
program to engage diverse medically underserved populations without a cancer
diagnosis in biospecimen donation for cancer genomic research. Participants were
recruited to in-depth community-based educational programs (~45-60-min duration)
or during open events in the community based on a convenience sampling. Programs
were offered in English and Spanish. An on-site mobile lab along with phlebotomy
services was provided at all programs and events to collect participant
biospecimen (blood) samples to be stored at the cancer center's Data Bank and
BioRepository (DBBR). The distributions for education, race/ethnicity, and gender
were similar across the event types. Most of the participants were women. The
analysis sample had a total of 311 participants, including 231 from the education
programs and 80 participants from open events. Those with a higher education
(college or more) were more likely to donate than those with a lower level of
education (high school or less) (45 vs 28 %, p = 0.007). Actual donation status
was not associated with age or race. Willingness to donate a biospecimen and
biospecimen donation rates followed the same pattern with respect to participants
with higher levels of education being more willing to donate and giving a blood
donation. Prior to outreach efforts, less than 6 % of specimens donated to DBBR
from healthy/non-cancer patients were from minority participants.
PMID- 27488841
TI - Total knee arthroplasty in patients with Ranawat type-II valgus arthritic knee
with a marked coronal femoral bowing deformity: comparison between computer
assisted surgery and intra-articular resection.
AB - BACKGROUND: Proper limb and component alignments as well as soft tissue balance
are vital for the longevity and optimal long-term outcomes of total knee
arthroplasty (TKA). This procedure is technically demanding in patients with
Ranawat type-II valgus arthritic knees with marked coronal femoral bowing.
Computer-assisted surgery (CAS) and intra-articular bone resection with TKA are
the treatments of choice for patients with ipsilateral extra-articular deformity.
In theory, both CAS and intra-articular bone resection are beneficial in Ranawat
type-II valgus arthritic knees with marked coronal femoral bowing deformity, but
the literature on this topic is sparse. We compared the benefits of using these
two techniques for TKA under this circumstance. METHODS: Patients who had Ranawat
type-II valgus arthritic knees and marked coronal femoral bowing deformity and
had undergone TKA at our hospital between 2005 and 2013 were enrolled in this
retrospective study. Patients treated with CAS were assigned to the CAS-TKA
group; patients treated with intra-articular bone resection were assigned to the
Bone-Resect-TKA group. Radiographic parameters and clinical outcomes
(International Knee Society (IKS) scores and patellar scores) in both groups were
compared. RESULTS: Forty-seven patients (50 knees) met the inclusion criteria: 22
knees in the CAS-TKA group and 28 knees in the Bone-Resect-TKA group. Lateral
retinaculum release was significantly (P = 0.008) higher in the Bone-Resect-TKA
group. The joint-line was significantly properly restored in the CAS-TKA group (P
= 0.011). The reconstructed mechanical axis was significantly (P = 0.012) closer
to normal in the CAS-TKA group than in the Bone-Resect-TKA group. For component
alignment, the femoral valgus and femoral flexion angles were significantly
better in the CAS-TKA group (P = 0.002 and P = 0.006, respectively), but not the
tibial valgus, tibial flexion, or patellar tilting angles. IKS scores and
patellar scores were not significantly different between groups at a mean follow
up of 60.2 months. CONCLUSIONS: CAS-TKA was effective for obtaining proper
alignment and joint-line restoration in patients with Ranawat type-II valgus
arthritic knees and marked coronal femoral bowing deformity, but not for yielding
better clinical outcomes. Additional large-scale prospective randomized cohort
studies with long-term follow-ups are necessary to make evidence-based
recommendations.
PMID- 27488842
TI - Pre- and postoperative correlation of patient-reported outcome measures with
standardized Timed Up and Go (TUG) test results in lumbar degenerative disc
disease.
AB - BACKGROUND: The Timed Up and Go (TUG) test is a reliable tool for evaluating
objective functional impairment (OFI) in patients with degenerative disc disease
before a surgical intervention. The aim of this study is to assess the validity
of the TUG test to measure change in function postoperatively. METHODS: In a
prospective two-center study, OFI was assessed by the TUG test in patients
scheduled for lumbar spine surgery, as well as 3 days (D3) and 6 weeks (W6)
postoperatively. At each time point, the TUG test results were correlated with
established subjective measures of pain intensity (visual analogue scale (VAS)
for back and leg pain), functional impairment (Oswestry Disability Index (ODI))
and health-related quality of life (HRQoL; Short Form-12 (SF12)). RESULTS: The
patient cohort comprised 136 patients with a mean age of 57.7 years; 76 were
males, 54 had a microdiscectomy for lumbar disc herniation, 58 a decompression
for a lumbar spinal stenosis, 24 had a surgical fusion procedure. The mean OFI t
score was 125.1 before surgery, and as patients improved on the subjective
measures in the postoperative interval, the OFI t-score likewise decreased to
118.8 (D3) and 103.4 (W6). The Pearson correlation coefficient (PCC) between the
OFI t-score and VAS leg pain was 0.187 preoperatively (p = 0.029) and 0.252 at W6
(p = 0.003). The PCC between OFI t-score and the ODI was 0.324 preoperatively (p
< 0.001) and 0.413 at W6 (p < 0.001). The PCC between OFI t-score and physical
HRQoL (SF12) was -0.091 preoperatively (p = 0.293) and -0.330 at W6 (p < 0.001).
CONCLUSIONS: The TUG test is sensitive to change, and reflects the postoperative
functional outcome even more exact than preoperatively, as indicated by better
correlation coefficients of the OFI t-score with subjective measures of pain
intensity, functional impairment and HRQoL.
PMID- 27488843
TI - Effects of aging and freezing/thawing sequence on quality attributes of bovine
Mm. gluteus medius and biceps femoris.
AB - OBJECTIVE: The effects of aging and freezing/thawing sequence on color,
physicochemical, and enzymatic characteristics of two beef muscles (Mm. gluteus
medius, GM and biceps femoris, BF) were evaluated. METHODS: Beef muscles at 3 d
postmortem were assigned to four different combinations of aging and
freezing/thawing sequence as follows; aging at 2 degrees C for 3 wk (A3, never
frozen control), freezing at -28 degrees C for 2 wk then thawing (F2,
frozen/thawed-only), aging at 2 degrees C for 3 wk, freezing at -28 degrees C for
2 wk then thawing (A3F2), and freezing at -28 degrees C for 2 wk, thawing then
further aging at 2 degrees C for 3 wk (F2A3). RESULTS: No significant
interactions between different aging/freezing/thawing treatments and muscle type
on all measurements were found. Postmortem aging, regardless of
aging/freezing/thawing sequence, had no impact on color stability of
frozen/thawed beef muscles (p<0.05). F2A3 resulted in higher purge loss than F2
and A3F2 treatments (p<0.05). A3F2 and F2A3 treatments resulted in lower shear
force of beef muscles compared to F2 (p<0.05). Although there was no significant
difference in glutathione peroxidase (GSH-Px) activity, F2A3 had the highest beta
N-acetyl glucominidase (BNAG) activity in purge, but the lowest BNAG activity in
muscle (p<0.05). GM muscle exhibited higher total color changes and purge loss,
and lower GSH-Px activity than BF muscle. CONCLUSION: The results from this
present study indicate that different combinations of aging/freezing/thawing
sequence would result in considerable impacts on meat quality attributes,
particularly thaw/purge loss and tenderness. Developing a novel freezing strategy
combined with postmortem aging will be beneficial for the food/meat industry to
maximize its positive impacts on tenderness, while minimizing thaw/purge loss of
frozen/thawed meat.
PMID- 27488844
TI - Effects of beta-Glucan on the Release of Nitric Oxide by Macrophages Stimulated
with Lipopolysaccharide.
AB - This research analyzed the effect of beta-glucan that is expected to alleviate
the production of the inflammatory mediator in macrophagocytes, which are
processed by the lipopolysaccharide (LPS) of Escherichia. The incubated layer was
used for a nitric oxide (NO) analysis. The DNA-binding activation of the small
unit of nuclear factor-kappaB was measured using the enzyme-linked immunosorbent
assay-based kit. In the RAW264.7 cells that were vitalized by Escherichia coli
(E. coli) LPS, the beta-glucan inhibited both the combatant and rendering phases
of the inducible NO synthase (iNOS)-derived NO. beta-Glucan increased the
expression of the heme oxygenase-1 (HO-1) in the cells that were stimulated by E.
coli LPS, and the HO-1 activation was inhibited by the tin protoporphyrin IX
(SnPP). This shows that the NO production induced by LPS is related to the
inhibition effect of beta-glucan. The phosphorylation of c-Jun N-terminal kinases
(JNK) and the p38 induced by the LPS were not influenced by the beta-glucan, and
the inhibitory kappaB-alpha (IkappaB-alpha) decomposition was not influenced
either. Instead, beta-glucan remarkably inhibited the phosphorylation of the
signal transducer and activator of transcription-1 (STAT1) that was induced by
the E. coli LPS. Overall, the beta-glucan inhibited the production of NO in
macrophagocytes that was vitalized by the E .coli LPS through the HO-1 induction
and the STAT1 pathways inhibition in this research. As the host immune response
control by beta-glucan weakens the progress of the inflammatory disease, beta
glucan can be used as an effective immunomodulator.
PMID- 27488845
TI - Effects of Physically Effective Neutral Detergent Fiber Content on Intake,
Digestibility, and Chewing Activity in Fattening Heifer Fed Total Mixed Ration.
AB - The objective of this study was to determine the effects of physically effective
neutral detergent fiber (peNDF) content in total mixed ration (TMR) on dry matter
intake, digestibility, and chewing activity in fattening Hanwoo (Bos taurus
coreanae) heifers. The experiment was designed as a replicated 3*3 Latin square
using 12 heifers. Fattening heifers were offered one of three diets [high (T1),
medium (T2), and low (T3) peNDF] obtained by different mixing times (3, 10, and
25 min) for the same TMR feed. The peNDF content of TMR was determined by
multiplying the proportion of dry matter retained by a 1.18 mm-screen in a Penn
State Particle Separator by the dietary NDF content. The peNDF1.18 content was
30.36%, 29.20%, and 27.50% for the T1, T2, and T3 diets, respectively (p<0.05).
Dry matter intake was not affected by peNDF content in TMR. Total weight gain in
T1 group was significantly higher (p<0.05) than in T2 and T3 groups. However,
weight gain did not differ between T2 and T3 groups. The feed conversion ratio
decreased with an increase in the peNDF content (T1: 12.18, T2: 14.17, and T3:
14.01 g/g). An increase in the peNDF content of TMR was associated with a linear
increase in the digestibility of dry matter, crude protein, crude fiber, neutral
detergent fiber, and acid detergent fiber (p<0.05). Also, an increase in peNDF
content of the TMR resulted in a linear increase in the number of chews in eating
and ruminating (p<0.05), and consequently in the number of total chews (p<0.05).
These results indicate that peNDF content affects digestibility and chewing
activity. Consequently, the peNDF content of TMR should be considered for
improving feed efficiency, digestibility, body weight gain, and performance in
fattening heifers.
PMID- 27488847
TI - Distinct transcriptional regulation of the two Escherichia coli transhydrogenases
PntAB and UdhA.
AB - Transhydrogenases catalyse interconversion of the redox cofactors NADH and NADPH,
thereby conveying metabolic flexibility to balance catabolic NADPH formation with
anabolic or stress-based consumption of NADPH. Escherichia coli is one of the
very few microbes that possesses two isoforms: the membrane-bound, proton
translocating transhydrogenase PntAB and the cytosolic, energy-independent
transhydrogenase UdhA. Despite their physiological relevance, we have only
fragmented information on their regulation and the signals coordinating their
counteracting activities. Here we investigated PntAB and UdhA regulation by
studying transcriptional responses to environmental and genetic perturbations. By
testing pntAB and udhA GFP reporter constructs in the background of WT E. coli
and 62 transcription factor mutants during growth on different carbon sources, we
show distinct transcriptional regulation of the two transhydrogenase promoters.
Surprisingly, transhydrogenase regulation was independent of the actual catabolic
overproduction or underproduction of NADPH but responded to nutrient levels and
growth rate in a fashion that matches the cellular need for the redox cofactors
NADPH and/or NADH. Specifically, the identified transcription factors Lrp, ArgP
and Crp link transhydrogenase expression to particular amino acids and
intracellular concentrations of cAMP. The overall identified set of regulators
establishes a primarily biosynthetic role for PntAB and link UdhA to respiration.
PMID- 27488848
TI - Out of the corner of the driver's eye: Peripheral processing of hazards in static
traffic scenes.
AB - Effective gaze control in traffic, based on peripheral visual information, is
important to avoid hazards. Whereas previous hazard perception research mainly
focused on skill-component development (e.g., orientation and hazard processing),
little is known about the role and dynamics of peripheral vision in hazard
perception. We analyzed eye movement data from a study in which participants
scanned static traffic scenes including medium-level versus dangerous hazards and
focused on characteristics of fixations prior to entering the hazard region. We
found that initial saccade amplitudes into the hazard region were substantially
longer for dangerous (vs. medium-level) hazards, irrespective of participants'
driving expertise. An analysis of the temporal dynamics of this hazard-level
dependent saccade targeting distance effect revealed that peripheral hazard-level
processing occurred around 200-400 ms during the course of the fixation prior to
entering the hazard region. An additional psychophysical hazard detection
experiment, in which hazard eccentricity was manipulated, revealed better
detection for dangerous (vs. medium-level) hazards in both central and peripheral
vision. Furthermore, we observed a significant perceptual decline from center to
periphery for medium (but not for highly) dangerous hazards. Overall, the results
suggest that hazard processing is remarkably effective in peripheral vision and
utilized to guide the eyes toward potential hazards.
PMID- 27488850
TI - Magnetic resonance imaging of pelvic floor dysfunction - joint recommendations of
the ESUR and ESGAR Pelvic Floor Working Group.
AB - OBJECTIVE: To develop recommendations that can be used as guidance for
standardized approach regarding indications, patient preparation, sequences
acquisition, interpretation and reporting of magnetic resonance imaging (MRI) for
diagnosis and grading of pelvic floor dysfunction (PFD). METHODS: The technique
included critical literature between 1993 and 2013 and expert consensus about MRI
protocols by the pelvic floor-imaging working group of the European Society of
Urogenital Radiology (ESUR) and the European Society of Gastrointestinal and
Abdominal Radiology (ESGAR) from one Egyptian and seven European institutions.
Data collection and analysis were achieved in 5 consecutive steps. Eighty-two
items were scored to be eligible for further analysis and scaling. Agreement of
at least 80 % was defined as consensus finding. RESULTS: Consensus was reached
for 88 % of 82 items. Recommended reporting template should include two main
sections for measurements and grading. The pubococcygeal line (PCL) is
recommended as the reference line to measure pelvic organ prolapse. The
recommended grading scheme is the "Rule of three" for Pelvic Organ Prolapse
(POP), while a rectocele and ARJ descent each has its specific grading system.
CONCLUSION: This literature review and expert consensus recommendations can be
used as guidance for MR imaging and reporting of PFD. KEY POINTS: * These
recommendations highlight the most important prerequisites to obtain a diagnostic
PFD-MRI. * Static, dynamic and evacuation sequences should be generally performed
for PFD evaluation. * The recommendations were constructed through consensus
among 13 radiologists from 8 institutions.
PMID- 27488851
TI - Dynamic contrast enhanced MR imaging for evaluation of angiogenesis of
hepatocellular nodules in liver cirrhosis in N-nitrosodiethylamine induced rat
model.
AB - PURPOSE: To investigate whether dynamic contrast -enhanced MRI (DCE-MRI) can
distinguish the type of liver nodules in a rat model with N-nitrosodiethylamine-
induced cirrhosis. METHODS: Liver nodules in cirrhosis were induced in 60 male
Wistar rats via 0.01 % N-nitrosodiethylamine in the drinking water for 35-100
days. The nodules were divided into three groups: regenerative nodule (RN),
dysplastic nodule (DN), and hepatocellular carcinoma (HCC). DCE-MRI was
performed, and parameters including transfer constant (Ktrans), rate constant
(Kep), extravascular extracellular space volume fraction (Ve), and initial area
under the contrast concentration versus time curve (iAUC) were measured and
compared. RESULTS: The highest Ktrans and iAUC values were seen in HCC, followed
by DN and RN (all P < 0.05). The area under the receiver operating characteristic
curve (AUROC) for DN and HCC were 0.738 and 0.728 for Ktrans and iAUC,
respectively. The AUROC for HCC were 0.850 and 0.840 for Ktrans and iAUC,
respectively. Ordinal logistic regression analysis showed that Ktrans had a high
goodness of fit (0.970, 95 % confidence interval, 13.751-24.958). CONCLUSION: DCE
MRI is a promising method to differentiate of liver nodules. Elevated Ktrans
suggested that the nodules may be transformed into HCC. KEY POINTS: * DCE-MRI is
promising for differentiating among RN, DN, and HCC * K trans and iAUC positively
correlated with malignancy degree of liver nodules * Elevated K trans suggests
that the nodules may be transformed into HCC.
PMID- 27488852
TI - An evaluation of the current patterns and practices of educational supervision in
postgraduate medical education in the UK.
AB - INTRODUCTION: Globally, clinical supervision has been widely adopted and studied.
But in the UK, another variant of supervision has developed in the form of
educational supervision. The quality of supervision remains highly variable and
inadequate time, investment and guidance hinders its ability to actually benefit
trainees. Therefore, undertaking a detailed study of the patterns and practices
in educational supervision to inform developments in supervisory practice would
be extremely beneficial. METHODS: In this mixed methods study, educational
supervisors and trainees working within a large London Trust were surveyed online
about their experiences of educational supervision. In addition, observations of
supervision sessions with a small group of supervisor and trainee pairs followed
up by semi-structured interviews were conducted. The quantitative data were
analyzed using statistical software via descriptive statistics. The qualitative
data underwent thematic framework analysis. RESULTS: Both the qualitative and
quantitative data revealed that whilst most junior doctors and supervisors value
the ideal of educational supervision as a process for engaging in mentoring
dialogues, it can become a tick box exercise, devaluing its usefulness and
purpose. Trainees highlighted the need for more frequent formal meeting along
with better preparation by supervisors. Supervisors would appreciate more support
from trusts to help them enhance supervision for trainees. CONCLUSION: The
effectiveness of educational supervision can be improved with trainees and
supervisors engaging in meaningful preparation and proactive communication before
meetings. During these formal meetings, improving the quality of feedback and
ensuring that regular mentoring dialogues occurred would be highly valuable.
PMID- 27488853
TI - Supercapacitors Based on Reduced Graphene Oxide Nanofibers Supported Ni(OH)2
Nanoplates with Enhanced Electrochemical Performance.
AB - Pseudocapacitive materials are critical to the development of supercapacitors but
usually suffer from poor conductivity and bad cycling property. Here, we describe
the production of novel graphene oxide nanofibers (GONFs) via a partial
oxidization and exfoliation method and concurrently report that highly
crystallized Ni(OH)2 nanoplates uniformly grow on reduced GONFs' outer graphene
nanosheets through the hydrothermal method. Because of their unique structure
with high electric conductivity, the rGONF/Ni(OH)2 composite exhibits superior
specific capacitance (SC), favorable rate capability and enhanced cycling
stability relative to other composites or hybrids, e.g., 1433 F g(-1) at 5 mV s(
1) scan rate, 986 F g(-1) at 40 mV s(-1), and 90.5% capacitance retention after
2000 cycles, and as-fabricated rGONF/Ni(OH)2//active carbon asymmetric
supercapacitor (ASC) exhibits a remarkable energy density and a 85.3% high
retention (44.1 Wh kg(-1) at 467 W kg(-1) and 37.6 Wh kg(-1) at 3185 W kg(-1))
with a wide potential window of 0-1.7 V. Therefore, this study shows that rGONFs
offers an exciting opportunity as substrate materials for supercapacior
applications and opens up a new pathway for design and manufacture of novel
supercapacitor electrode materials.
PMID- 27488854
TI - Grueneberg Glomeruli in the Olfactory Bulb are Activated by Odorants and Cool
Temperature.
AB - Neurons of the Grueneberg ganglion respond to cool temperatures as well as to
distinct odorants and extend axonal processes to the olfactory bulb of the brain.
Analyses of transgenic mice, in which Grueneberg ganglion neurons and their axons
are labeled, revealed that these axons innervated nine distinct glomeruli
distributed in a characteristic topographical pattern in dorsal, lateral,
ventral, and medial regions of rather posterior areas in the bulb. To assess
activation of these glomeruli (hereinafter designated as Grueneberg glomeruli)
upon stimulation of Grueneberg ganglion neurons, mice were exposed to the odorant
2,3-dimethylpyrazine (2,3-DMP) and the expression of the activity-dependent
marker c-Fos in juxtaglomerular cells of the relevant glomeruli was monitored. It
was found that all of these glomeruli were activated, irrespective of their
localization in the bulb. To verify that the activation of juxtaglomerular cells
in Grueneberg glomeruli was indeed based on stimulation of Grueneberg ganglion
neurons, the 2,3-DMP-induced responses in these glomeruli were investigated in
mice lacking the cyclic nucleotide-gated channel CNGA3 which is critical for
chemo- and thermosensory signal transduction in Grueneberg ganglion neurons. This
approach revealed that elimination of CNGA3 led to a reduction of the odorant
induced activity in Grueneberg glomeruli, indicating that the activation of these
glomeruli is based on a preceding stimulation of the Grueneberg ganglion.
Analyzing whether Grueneberg glomeruli in the bulb might also process
thermosensory information, it was found that upon exposure to coolness,
Grueneberg glomeruli were activated. Investigating mice lacking CNGA3, the
activation of these glomeruli by cool temperatures was attenuated.
PMID- 27488856
TI - A H(+)-triggered bubble-generating nanosystem for killing cancer cells.
AB - We constructed a H(+)-triggered bubble-generating nanosystem (BGNS), which
generated CO2 bubbles in the acidic environment of lysosomes after being
internalized by cancer cells. The quickly generated bubbles caused enhanced
lysosomal membrane permeabilization. As expected, H(+)-triggered BGNS possessed
remarkable cytotoxicity against MCF-7 breast cancer cells, and successfully
overcame the multidrug resistance of MCF-7/ADR cells.
PMID- 27488855
TI - Atorvastatin Attenuates Ischemia/Reperfusion-Induced Hippocampal Neurons Injury
Via Akt-nNOS-JNK Signaling Pathway.
AB - Ischemia-induced brain damage leads to apoptosis like delayed neuronal death in
selectively vulnerable regions, which could further result in irreversible
damages. Previous studies have demonstrated that neurons in the CA1 area of
hippocampus are particularly sensitive to ischemic damage. Atorvastatin (ATV) has
been reported to attenuate cognitive deficits after stroke, but precise mechanism
for neuroprotection remains unknown. Therefore, the aims of this study were to
investigate the neuroprotective mechanisms of ATV against ischemic brain injury
induced by cerebral ischemia reperfusion. In this study, four-vessel occlusion
model was established in rats with cerebral ischemia. Rats were divided into five
groups: sham group, I/R group, I/R+ATV group, I/R+ATV+LY, and I/R+SP600125 group.
Cresyl violet staining was carried out to examine the neuronal death of
hippocampal CA1 region. Immunoblotting was used to detect the expression of the
related proteins. Results showed that ATV significantly protected hippocampal CA1
pyramidal neurons against cerebral I/R. ATV could increase the phosphorylation of
protein kinase B (Akt1) and nNOS, diminished the phosphorylation of JNK3 and c
Jun, and further inhibited the activation of caspase-3. Whereas, all of the
aforementioned effects of ATV were reversed by LY294002 (an inhibitor of Akt1).
Furthermore, pretreatment with SP600125 (an inhibitor of JNK) diminished the
phosphorylation of JNK3 and c-Jun, and further inhibited the activation of
caspase-3 after cerebral I/R. Taken together, our results implied that Akt
mediated phosphorylation of nNOS is involved in the neuroprotection of ATV
against ischemic brain injury via suppressing JNK3 signaling pathway that provide
a new experimental foundation for stroke therapy.
PMID- 27488858
TI - HIV encephalitis with subcortical tau deposition: imaging pathology in vivo using
F-18 THK 5117.
PMID- 27488857
TI - Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's
disease.
AB - PURPOSE: The cannabinoid type 2 receptor (CB2R) is expressed by immune cells such
as monocytes and macrophages. In the brain, CB2R is primarily found on microglia.
CB2R upregulation has been reported in animal models of Alzheimer's disease, with
a preferential localization near amyloid beta (Abeta) plaques, and in patients
post mortem. We performed in vivo brain imaging and kinetic modelling of the CB2R
tracer [11C]NE40 in healthy controls (HC) and in patients with Alzheimer's
disease (AD) to investigate whether higher CB2R availability regionally
colocalized to Abeta deposits is present in vivo. METHODS: Dynamic 90-min
[11C]NE40 PET scans were performed in eight HC and nine AD patients with full
kinetic modelling using arterial sampling and metabolite correction and partial
volume correction. All AD patients received a static [11C]PIB scan 40 min after
injection. In four HC, a retest scan with [11C]NE40 PET was performed within 9
weeks to investigate test-retest characteristics. RESULTS: [11C]NE40 was
metabolized quickly leading to 50 % of intact tracer 20 min after injection and
20 % at 90 min. A two-tissue kinetic model fitted most of the time-activity
curves best; both binding potential (BPND) and distribution volume (V T)
parameters could be used. Brain uptake was generally low with an average K 1
value of 0.07 ml/min/ml tissue. V T and BPND were in the range of 0.7 - 1.8 and
0.6 - 1.6, respectively. Test values in HC were about 30 % for V T and BPND. AD
patients showed overall significantly lower CB2R binding. No relationship was
found between regional or global amyloid load and CB2R availability. CONCLUSION:
Kinetic modelling of [11C]NE40 is possible with a two-tissue reversible model. In
contrast to preclinical and post-mortem data, [11C]NE40 PET shows lower CB2R
availability in vivo in AD patients, with no relationship to Abeta plaques. A
possible explanation for these findings is that [11C]NE40 binds to CB2R with
lower affinity and/or selectivity than to CB1R.
PMID- 27488859
TI - Changes in P2Y12 reaction units after switching treatments from prasugrel to
clopidogrel in Japanese patients with acute coronary syndrome followed by
elective coronary stenting.
AB - Patients with ischemic heart disease are administered a dual antiplatelet therapy
after percutaneous coronary intervention. This consists of aspirin and
thienopyridine, which can be switched from prasugrel to clopidogrel. However, the
impact of switching is unknown. This study aimed to determine the efficacy and
safety of switching from prasugrel to clopidogrel in Japanese patients. One
hundred and thirty-six patients with acute coronary syndrome scheduled to undergo
percutaneous coronary intervention and patients with coronary artery disease
requiring elective coronary stenting were enrolled. Patients were randomly
assigned into the following groups: prasugrel for 6 weeks at loading/maintenance
doses of 20/3.75 mg (Continued Group; n = 68) or prasugrel at 20/3.75 mg for 2
weeks followed by clopidogrel at 75 mg for 4 weeks (Switched Group; n = 68).
Aspirin (loading dose/maintenance dose 324/81-100 mg/day) was coadministered in
both groups. The primary endpoint was the mean P2Y12 reaction unit (PRU) at week
6 and the secondary endpoint was the PRU in groups subdivided based on the
presence of CYP2C19 gene polymorphisms. At week 6, the PRU was significantly
lower in the Continued Group relative to the Switched Group (140.7 and 183.0,
respectively; P < 0.001), which was also evident after correction with the
baseline values (144.1 vs. 176.6, respectively; P = 0.005). Extensive and poor
metabolizers in the Switched Group, based on CYP2C19 gene polymorphisms, had
significantly higher PRU values than those in the Continued Group. Thus,
switching treatments from prasugrel to clopidogrel significantly increased the
PRU in patients receiving antiplatelet therapy subsequent to percutaneous
coronary intervention. Clinical Trial Registration UMIN ID, UMIN000015122.
PMID- 27488860
TI - Comments regarding: The benefits of using a vacuum-assisted socket system to
improve balance and gait in elderly transtibial amputees by Samitier et al.
PMID- 27488861
TI - Reply to: Comments regarding: The benefits of using a vacuum-assisted socket
system to improve balance and gait in elderly transtibial amputees by Samitier et
al.
PMID- 27488862
TI - Intraspinal cavernous bleeding during early pregnancy.
PMID- 27488864
TI - Salmonella in Wild Birds Utilizing Protected and Human Impacted Habitats, Uganda.
AB - As human populations in Africa expand, humans encroach and modify wildlife
habitats for farming, fishing, tourism, or settlement. Anthropogenic activities
in shared environments may promote transmission of zoonotic pathogens between
humans, domestic animals, and wildlife. Between July 2012 and February 2014, we
evaluated Salmonella prevalence, serovars, genotypes, and antibiotic resistant
phenotypes in resident and migratory birds utilizing human-impacted habitats in
northwestern Lake Victoria and protected habitats in Queen Elisabeth National
Park. Salmonella occurrence in the urban environment was assessed by sampling
storm-water and wastewater from a channel that drains Kampala City into Lake
Victoria. Salmonella was detected in 4.3% pooled bird fecal samples, and 57.1% of
environmental samples. While birds in impacted and protected areas shared
serovars, the genotypes were distinct. We found distinct strains in birds and the
environment suggesting some strains in birds are host adapted, and strains
circulating in the environment may not necessarily disseminate to birds.
Conversely, birds in both impacted and protected areas shared strains with the
urban environment, suggesting Salmonella disseminates between impacted
environments and birds across sites. Overall, more strains were observed in the
urban environment compared to birds, and poses risk of Salmonella reemergence in
birds and transmission across species and space.
PMID- 27488863
TI - Long-term treatment with thiamine as possible medical therapy for Friedreich
ataxia.
AB - Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic
metabolism; its deficiency causes disorders affecting both the peripheral and
central nervous system. Previous studies reported low thiamine levels in
cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia
(FRDA). We investigated the effect of long-term treatment with thiamine in FRDA,
evaluating changes in neurological symptoms, echocardiographic parameters, and
plasma FXN mRNA levels. Thirty-four consecutive FRDA patients have been
continuously treated with intramuscular thiamine 100 mg twice a week and have
been assessed with the Scale for the Assessment and Rating of Ataxia (SARA) at
baseline, after 1 month, and then every 3 months during treatment. Thiamine
administration ranged from 80 to 930 days and was effective in improving total
SARA scores from 26.6 +/- 7.7 to 21.5 +/- 6.2 (p < 0.02). Moreover, deep tendon
reflexes reappeared in 57 % of patients with areflexia at baseline, and
swallowing improved in 63 % of dysphagic patients. Clinical improvement was
stable in all patients, who did not show worsening even after 2 years of
treatment. In a subgroup of 13 patients who performed echocardiogram before and
during treatment, interventricular septum thickness reduced significantly (p <
0.02). Frataxin mRNA blood levels were modestly increased in one-half of treated
patients. We suppose that a focal thiamine deficiency may contribute to a
selective neuronal damage in the areas involved in FRDA. Further studies are
mandatory to evaluate thiamine role on FXN regulation, to exclude placebo effect,
to verify our clinical results, and to confirm restorative and neuroprotective
action of thiamine in FRDA.
PMID- 27488865
TI - Green tea cultivar 'Benifuuki' potentiates split vaccine-induced immunoglobulin A
production.
AB - Influenza is a widespread disease caused by infection with the influenza virus.
Vaccination is considered to be the main countermeasure against influenza. A
split vaccine is widely used to avoid severe adverse events, and it induces
strong humoral immunity. However, the split vaccine alone cannot elicit mucosal
immunity, including IgA production, and its preventative effects are limited.
Here, we show that the green tea cultivar 'Benifuuki' extract enhanced the effect
of a split vaccine on mucosal immunity. The frequency of IgA+ cells was increased
in lung and Peyer's patch that received Benifuuki diet. Secretion of
hemagglutinin-specific mucosal IgA, which is closely linked to the prevention of
viral infection, was significantly increased in the bronchoalveolar lavage fluid
of split vaccine-immunized BALB/c mice that were administered green tea Benifuuki
extract. Our findings suggest that Benifuuki intake enhanced the effects of the
split vaccine on mucosal immunity.
PMID- 27488866
TI - Optimal control therapy and vaccination for special HIV-1 model with delay.
AB - In this paper, we consider a four dimensional model of the human immunodeficiency
virus-1 (HIV-1) with delay, which is an extension of some three dimensional
models. We approach the treatment problem by adding two controllers to the system
for inhibiting viral production. The optimal controller [Formula: see text] is
considered for vaccine and [Formula: see text] for the drug. The Pontryagin
maximum principle with delay is used to characterize these optimal controls. At
the end, numerical results are presented to illustrate the optimal solutions. The
validity of the model was confirmed by proper semi-quantitative simulation of
some clinical data. The model was used to predict the possible beneficial effects
of vaccine and anti-retroviral drug administration in HIV-1 disease.
PMID- 27488867
TI - The undesirable retroactive changes to Rule 8 of the International Code of
Nomenclature of Prokaryotes.
AB - Changes have been made to Rule 8 of the International Code of Nomenclature of
Prokaryotes that caters for the names and nomenclatural types of classes and
subclasses. The changes are retroactive because they are not specifically
restricted in time. Consequently, that influences names of classes and subclasses
and their nomenclatural types that have previously appeared in print.
PMID- 27488869
TI - Erdheim-Chester Disease with Emperipolesis: A Unique Case Involving the Heart.
AB - Histiocytosis is an uncommon disease characterized by excessive accumulation of
histiocytes. Here, we report a rare case of non-Langerhans-cell histiocytosis in
a 51-year-old woman who presented with severe symptoms of pericardial effusion.
Radiologic investigation also detected multiple bone (lower limbs, vertebrae,
ribs, and ilium) lesions. Resected pericardium showed abundant mono- or multi
nucleated non-foamy histiocytes (CD68+/CD163+/S-100+/CD1alpha-/langerin-) in a
fibroinflammatory background. The histiocytes demonstrated emperipolesis of
lymphocytes, a hallmark feature of Rosai-Dorfman disease (RDD). However,
molecular analysis revealed a BRAF V600E mutation of the proliferating
histiocytes, highlighting the neoplastic features frequently observed in another
non-Langerhans-cell histiocytosis known as Erdheim-Chester Disease (ECD). We
consider this case to be a unique presentation of ECD harboring some RDD-like
cells with emperipolesis, but not a case of RDD with a BRAF mutation concerning
its clinical manifestation (involvement of the heart and bones) and neoplastic
features.
PMID- 27488870
TI - The Prevalence of Founder Mutations among Individuals from Families with Familial
Pancreatic Cancer Syndrome.
AB - PURPOSE: Familial pancreatic cancer describes families with at least two first
degree relatives with pancreatic cancer that do not fulfil the criteria of other
inherited tumor syndromes with increased risks of pancreatic cancer. Although
much has been learned regarding the aggregation of pancreatic cancer in some
families, the genetic basis for this familial aggregation is poorly understood.
This study evaluated the prevalence of 10 Polish founder mutations in four genes
among individuals from families with diagnosed familial pancreatic cancer
syndrome and assessed their possible association with the familial pancreatic
cancer (FPC) risk in Poland. MATERIALS AND METHODS: In this study, 400 FPC
individuals and 4,000 control subjects were genotyped for founder mutations in
BRCA1 (5382insC, 4153delA, C61G), CHEK2 (1100delC, IVS2+1G>A, del5395, I157T),
NBS1 (657del5), and PALB2 (509_510delGA, 172_175delTTGT) genes. RESULTS: A
statistically significant association was observed between the 172_175delTTGT
mutation of the PALB2 gene and an increased risk of FPC syndrome (odds ratio
[OR], 10.05; p=0.048). In addition, an increased risk of cancer was observed in
the FPC family members with a BRCA1 mutation (OR, 6.72; p=0.006). Novel
associations were found between the FPC family members with cancer and CHEK2
mutations (OR, 2.26; p=0.008) with a noticeable contribution of the missense
variant, I157T of CHEK2 (OR, 2.17; p=0.026). CONCLUSION: The founder mutations in
the genes, BRCA1, PALB2, and CHEK2, cause a small percentage of familial
pancreatic cancer syndrome in the Polish population. Following confirmation in
larger studies, these mutations can be added to the panel of genes to be tested
in families with a diagnosis of FPC syndrome.
PMID- 27488871
TI - Induction of Apoptosis in Intestinal Toxicity to a Histone Deacetylase Inhibitor
in a Phase I Study with Pelvic Radiotherapy.
AB - PURPOSE: When integrating molecularly targeted compounds in radiotherapy,
synergistic effects of the systemic agent and radiation may extend the limits of
patient tolerance, increasing the demand for understanding the pathophysiological
mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO)
study, we investigated mechanisms of adverse effects in response to the histone
deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA)
when administered as a potential radiosensitiser. MATERIALS AND METHODS: This
phase I study for advanced gastrointestinal carcinoma was conducted in sequential
patient cohorts exposed to escalating doses of vorinostat combined with standard
fractionated palliative radiotherapy to pelvic target volumes. Gene expression
microarray analysis of the study patient peripheral blood mononuclear cells
(PBMC) was followed by functional validation in cultured cell lines and mice
treated with SAHA. RESULTS: PBMC transcriptional responses to vorinostat,
including induction of apoptosis, were confined to the patient cohort reporting
dose-limiting intestinal toxicities. At relevant SAHA concentrations, apoptotic
features (annexin V staining and caspase 3/7 activation, but not poly-(ADP
ribose)-polymerase cleavage) were observed in cultured intestinal epithelial
cells. Moreover, SAHA-treated mice displayed significant weight loss. CONCLUSION:
The PRAVO study design implemented a strategy to explore treatment toxicity
caused by an HDAC inhibitor when combined with radiotherapy and enabled the
identification of apoptosis as a potential mechanism responsible for the dose
limiting effects of vorinostat. To the best of our knowledge, this is the first
report deciphering mechanisms of normal tissue adverse effects in response to an
HDAC inhibitor within a combined-modality treatment regimen.
PMID- 27488872
TI - Inhibition of SKP2 Sensitizes Bromocriptine-Induced Apoptosis in Human
Prolactinoma Cells.
AB - PURPOSE: Prolactinoma (prolactin-secreting pituitary adenoma) is one of the most
common estrogen-related functional pituitary tumors. As an agonist of the
dopamine D2 receptor, bromocriptine is used widely to inhibit prolactinoma
progression. On the other hand, it is not always effective in clinical
application. Although a dopamine D2 receptor deficiency contributes to the
impaired efficiency of bromocriptine therapy to some extent, it is unknown
whether there some other underlying mechanisms leading to bromocriptine
resistance in prolactinoma treatment. That is the main point addressed in this
project. MATERIALS AND METHODS: Human prolactinoma samples were used to analyze
the S-phase kinase associated protein 2 (SKP2) expression level. Nutlin
3/adriamycin/cisplatin-treated GH3 and MMQ cells were used to analyze apoptosis
in SKP2 overexpression or knockdown cells. SKP2 expression and the interaction
partners of SKP2 were also detected after a bromocriptine treatment in 293T.
Apoptosis was analyzed in C25 and bromocriptine-treated GH3 cells. RESULTS:
Compared to normal pituitary samples, most prolactinoma samples exhibit higher
levels of SKP2 expression, which could inhibit apoptosis in a p53-dependent
manner. In addition, the bromocriptine treatment prolonged the half-life of SKP2
and resulted in SKP2 overexpression to a greater extent, which in turn
compromised its pro-apoptotic effect. As a result, the bromocriptine treatment
combined with C25 (a SKP2 inhibitor) led to the maximal apoptosis of human
prolactinoma cells. CONCLUSION: These findings indicated that SKP2 inhibition
sensitized the prolactinoma cells to bromocriptine and helped promote apoptosis.
Moreover, a combined treatment of bromocriptine and C25 may contribute to the
maximal apoptosis of human prolactinoma cells.
PMID- 27488873
TI - Phase II Study of Irinotecan and Cisplatin Combination Chemotherapy in
Metastatic, Unresectable Esophageal Cancer.
AB - PURPOSE: The objective of this multicenter phase II study was to evaluate the
efficacy and safety of irinotecan and cisplatin combination chemotherapy in
metastatic, unresectable esophageal cancer. MATERIALS AND METHODS: Patients were
treated with irinotecan 65 mg/m2 and cisplatin 30 mg/m2 on days 1 and 8 of each
21-day treatment cycle. The primary endpoint was response rate, and secondary
endpoints were survival, duration of response, initial metabolic response rate,
and toxicity. RESULTS: A total of 27 patients with squamous cell histology were
enrolled in the study. The median age of the patients was 61 years. The objective
response rate of the 20 patients in the perprotocol group was 30.0% (90%
confidence interval [CI], 13.2 to 46.9). The median follow-up duration was 10.0
months, and the median progression-free survival and overall survival were 4.5
months (95% CI, 1.6 to 6.2) and 8.8 months (95% CI, 4.7 to 10.5), respectively.
Four of 13 patients (30.8%) evaluated showed initial metabolic response. The
median duration of response for partial responders was 5.0 months (range, 3.4 to
8.0 months). The following grade 3/4 treatment-related hematologic toxicities
were reported: neutropenia (40.7%), anaemia (22.2%), and thrombocytopenia (7.4%).
Two patients experienced febrile neutropenia. The most common grade 3/4 non
hematologic toxicities were asthenia (14.8%) and diarrhoea (11.1%). CONCLUSION:
Irinotecan and cisplatin combination chemotherapy showed modest anti-tumour
activity and manageable toxicity for patients with metastatic, unresectable
esophageal cancer.
PMID- 27488874
TI - Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of
Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients.
AB - PURPOSE: The purpose of this study was to investigate the clinical features of
epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status
(mutation, variant of uncertain significance [VUS], or wild type). MATERIALS AND
METHODS: We analyzed 116 patients whose BRCA1/2 genetic test results were
available for mutation type and clinical features, including progression-free
survival (PFS), overall survival (OS), and response rate. These characteristics
were compared according to BRCA1/2 mutation status. RESULTS: Thirty-seven
(37/116, 31.9%) BRCA1/2mutations were identified (BRCA1, 30; BRCA2, 7). Mutation
of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients
(5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal
histories of breast cancer were observed in 48.6% of patients with BRCA1/2
mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients
with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed
longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences
were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and
BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively). CONCLUSION:
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type.
Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.
PMID- 27488875
TI - Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial
Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer.
AB - PURPOSE: The tertiary lymphoid structure (TLS) is an important source of tumor
infiltrating lymphocytes (TILs), which have a strong prognostic and predictive
value in triple-negative breast cancer (TNBC). A previous study reported that the
levels of CXCL13 mRNA expression were associated with TLSs, but measuring the
gene expression is challenging in routine practice. Therefore, this study
evaluated the MECA79-positive high endothelial venule (HEV) densities and their
association with the histopathologically assessed TLSs in biopsy samples. In
addition, the relationship of TLSs with the CXCL13 transcript levels and clinical
outcomes were examined. MATERIALS AND METHODS: A total of 108 TNBC patients
treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and
TLSs were measured histopathologically using hematoxylin and eosin-stained
slides. The HEV densities and TIL subpopulations were measured by
immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels
using a NanoString assay (NanoString Technologies). RESULTS: The mean number of
HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs,
HEV density, and CXCL13 expression showed robust correlations with each other. A
lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density,
CD20-positive cell density, and CXCL13 expression were significant predictors of
a pathologic complete response (pCR). Higher CD8-positive cell density and levels
of CXCL13 expression were significantly associated with a better disease-free
survival rate. CONCLUSION: MECA79-positive HEV density in pre-NAC biopsies is an
objective and quantitative surrogate marker of TLS and might be a valuable tool
for predicting pCR of TNBC in routine pathology practice.
PMID- 27488877
TI - Factors associated with increasing campylobacteriosis incidence in Michigan, 2004
2013.
AB - This study was conducted to examine the incidence trend of campylobacteriosis in
Michigan over a 10-year period and to investigate risk factors and clinical
outcomes associated with infection. Campylobacter case data from 2004 to 2013 was
obtained from the Michigan Disease Surveillance System. We conducted statistical
and spatial analyses to examine trends and identify factors linked to
campylobacteriosis as well as ecological associations using animal density data
from the National Agricultural Statistics Service. An increasing trend of
Campylobacter incidence and hospitalization was observed, which was linked to
specific age groups and rural residence. Cases reporting ruminant contact and
well water as the primary drinking source had a higher risk of
campylobacteriosis, while higher cattle density was associated with an increased
risk at the county level. Additional studies are needed to identify age-specific
risk factors and examine prevalence and transmission dynamics in ruminants and
the environment to aid in the development of more effective preventive
strategies.
PMID- 27488876
TI - Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic
Breast Cancer: Korean Multi-center Phase IV Clinical Study Results.
AB - PURPOSE: Eribulin mesilate was approved for the treatment of patients with
locally advanced or metastatic breast cancer (MBC), who had received at least two
chemotherapeutic regimens, including anthracycline and taxane. On the other hand,
the efficacy and safety information of eribulin in Korean patients is limited by
the lack of clinical trials. MATERIALS AND METHODS: In this multicenter, open
label, single-arm, phase IV study, locally advanced or MBC patients were enrolled
between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2
dose of eribulin was administered on days 1 and 8 of every 21 days. The primary
endpoint was the frequency and intensity of the treatment emergent adverse event.
The secondary endpoint was the disease control rate, which included the rate of
complete responses, partial responses, and stable disease. RESULTS: A total of
101 patients received at least one dose of eribulin and were included in the
safety set. The patients received a total of 543 treatment cycles, with a median
of three cycles (range, 1 to 31 cycles). The most common adverse event was
neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological
adverse events included alopecia, decrease in appetite, fatigue/asthenia, and
myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27
patients (26.7%), including grade 3 in two patients. Disease control rate was
52.7% and 51.3% of patients in the full analysis set and per-protocol set,
respectively. CONCLUSION: This study demonstrated the feasible safety profile and
activity of eribulin in Korean patients with MBC.
PMID- 27488879
TI - Erratum to: Complete genome sequence of Colocasia bobone disease-associated
virus, a putative cytorhabdovirus infecting taro.
PMID- 27488878
TI - "Cytoplasmic domain effects on exposure of co-receptor-binding sites of HIV-1
Env".
AB - We defined the effects of the cytoplasmic domain (CT) of the Env glycoprotein on
co-receptor usage of HIV-1 by reciprocal exchanges of regions containing V3-V5
loops between CD4-dependent and CD4-independent isolates. Primary HIV-1 isolate
Env clones CD8 CXCR4-tropic 92UG046 CT84 with an 84-aa truncated CT domain, CD4
CXCR4-tropic 92UG046, and CD4 CCR5-tropic SF162 with full-length (FL) CT domains
were used for comparison. The parental 92UG046 Env with CT84 was not fusogenic,
but a chimeric SF162 V3-V5-CT84 with an 84-aa truncated CT domain, which
demonstrated a switched co-receptor specificity, exhibited syncytium-formation
activity with 3T3T4X4 cells. The wild-type (WT) SF162 Env with CT84 or full
length CT was fusogenic in 3T3T4R5 cells. By exchange of V3-V5 loops, we were
able to alter WT SF162 to switch its co-receptor preference, which was not
dependent on CT domain length. These results provide evidence that CT domains can
induce conformational changes in functional regions of gp120 and determine
receptor tropism but do not modulate HIV-1 co-receptor specificity.
PMID- 27488880
TI - Ontario plans to stop funding high dose opioids.
PMID- 27488881
TI - Isolation of Treponema DNA from Necrophagous Flies in a Natural Ecosystem.
AB - BACKGROUND: Recently, the World Health Organization launched a campaign to
eradicate the tropical disease yaws, caused by the bacterium Treponema pallidum
subsp. pertenue; however, for decades researchers have questioned whether flies
act as a vector for the pathogen that could facilitate transmission. METHODS: A
total of 207 fly specimens were trapped in areas of Africa in which T. pallidum
induced skin ulcerations are common in wild baboons; 88 flies from Tarangire
National Park and 119 from Lake Manyara National Park in Tanzania were analyzed
by PCR for the presence of T. pallidum DNA. FINDINGS: We report that in the two
study areas, T. pallidum DNA was found in 17-24% of wild-caught flies of the
order Diptera. Treponemal DNA sequences obtained from many of the flies match
sequences derived from nearby baboon T. pallidum strains, and one of the fly
species with an especially high prevalence of T. pallidum DNA, Musca sorbens, has
previously been shown to transmit yaws in an experimental setting.
INTERPRETATION: Our results raise the possibility that flies play a role in yaws
transmission; further research is warranted, given how important understanding
transmission is for the eradication of this disfiguring disease.
PMID- 27488882
TI - Cell cycle arrest and mechanism of apoptosis induction in H400 oral cancer cells
in response to Damnacanthal and Nordamnacanthal isolated from Morinda citrifolia.
AB - Oral cancer is the eleventh most prevalent cancer worldwide. The most prevalent
oral cancer is oral squamous cell carcinoma (OSCC). Damnacanthal (DAM) and
nordamnacanthal (NDAM), the anthraquinone compounds, are isolated from the root
of Morinda citrifolia L. (Noni), which has been used for the treatment of several
chronic diseases including cancer. The objectives of this study were to evaluate
the cytotoxicity, cell death mode, cell cycle, and the molecular mechanism of
apoptosis induced by DAM and NDAM on OSCC. The cytotoxic effects of these
compounds against OSCC cell lines were determined by MTT assay. The cell death
mode was analysed by DNA laddering and FITC-annexin V/PI flow cytometric assays.
In addition, the mechanism of apoptosis induced by DAM and NDAM was detected
using mitochondrial membrane potential, Cytochrome c, and caspases assays.
Finally, the effect of DAM and NDAM on cell cycle phase distribution of OSCC
cells was detected by flow cytometry. In the present study, DAM and NDAM showed
cytotoxicity towards OSCC cell lines and the maximum growth inhibition for both
compounds was observed in H400 cells with IC50 value of 1.9 and 6.8 MUg/ml,
respectively, after 72 h treatment. The results also demonstrated the inhibition
of H400 OSCC cells proliferation, internucleosomal cleavage of DNA, activation of
intrinsic apoptosis pathway, and cell cycle arrest caused by DAM and NDAM.
Therefore, these findings suggest that DAM and NDAM can be potentially used as
antitumor agents for oral cancer therapy.
PMID- 27488884
TI - Saturation dynamics and working limits of saturated absorption cavity ringdown
spectroscopy.
AB - Cavity ringdown spectroscopy (CRDS) in the linear absorption regime is a well
established method for sensitive trace gas detection, but only a few studies have
addressed quantitative measurements in the presence of a saturated sample. In
fact, saturation is usually avoided in order to escape from the required complex
modeling of the saturation process that depends on the characteristics of the
absorbing species, its interaction with the surrounding gas as well as on the
temporal and spectral characteristics of the cavity excitation. Conversely, the
novel saturated-absorption cavity ringdown spectroscopy approach (SCAR/Sat-CRDS)
takes advantage of sample saturation in order to allow one to extract both the
gas absorption and the empty cavity loss rates from a single ringdown event.
Using a new continuous-wave infrared CRD spectrometer equipped with a tunable
narrow-bandwidth high-power OPO laser system and a 18 bit digitizer, the
transient dynamics of absorption saturation and the working limits of the Sat
CRDS approach in terms of its ability to extract reliable trace gas
concentrations have been experimentally studied in this work. Using a strong
methane transition as a test case, the excitation power P0 and saturation power
PS have been systematically varied to explore a wide range of saturation regimes.
At pressures 5 MUbar < p < 2 mbar, the saturation intensity revealed a nearly
linear pressure dependence showing that non-collisional processes contribute to
the overall relaxation. A ratio of P0/PS ~ 15 turned out to be optimal with
working limits of 5 < P0/PS < 300. Moreover, the ratio of the absorption and
empty cavity loss rates, gammag/gammac, has been varied to test the dynamic range
of the method. At gammag > gammac, a pronounced coupling between the two
parameters has been observed. Finally, a standard error analysis was performed
revealing that the Sat-CRDS approach holds its advantages over conventional CRDS
implementations in particular when the attainable ultimate detection sensitivity
is limited by uncertainties in the empty cavity ringdown constant.
PMID- 27488883
TI - A high-throughput AO/PI-based cell concentration and viability detection method
using the Celigo image cytometry.
AB - To ensure cell-based assays are performed properly, both cell concentration and
viability have to be determined so that the data can be normalized to generate
meaningful and comparable results. Cell-based assays performed in immuno
oncology, toxicology, or bioprocessing research often require measuring of
multiple samples and conditions, thus the current automated cell counter that
uses single disposable counting slides is not practical for high-throughput
screening assays. In the recent years, a plate-based image cytometry system has
been developed for high-throughput biomolecular screening assays. In this work,
we demonstrate a high-throughput AO/PI-based cell concentration and viability
method using the Celigo image cytometer. First, we validate the method by
comparing directly to Cellometer automated cell counter. Next, cell concentration
dynamic range, viability dynamic range, and consistency are determined. The high
throughput AO/PI method described here allows for 96-well to 384-well plate
samples to be analyzed in less than 7 min, which greatly reduces the time
required for the single sample-based automated cell counter. In addition, this
method can improve the efficiency for high-throughput screening assays, where
multiple cell counts and viability measurements are needed prior to performing
assays such as flow cytometry, ELISA, or simply plating cells for cell culture.
PMID- 27488885
TI - Two years into the Sunshine Act: synopsis of opportunities, challenges,
learnings, and potential implications.
AB - Responsible transparency helps to promote integrity between industry and
researchers and has the potential to increase public trust. As part of its
inevitable evolution, the Open Payments database is likely to have opportunities
to increase and improve the context around the data that it reports, thus leading
to a decrease in the currently encountered confusion and misinterpretation of the
data. A major challenge faced by the Centers for Medicare and Medicaid Services
is to make the data more informative and educational, to allow the Sunshine Act
to meet its transparency goals while improving healthcare innovation.
PMID- 27488886
TI - Carotid baroreflex control of heart rate is enhanced, while control of mean
arterial pressure is preserved during whole body heat stress in young healthy
men.
AB - Whole body heat stress (WBH) results in numerous cardiovascular alterations that
ultimately reduce orthostatic tolerance. While impaired carotid baroreflex (CBR)
function during WBH has been reported as a potential reason for this decrement,
study design considerations may limit interpretation of previous findings. We
sought to test the hypothesis that CBR function is unaltered during WBH. CBR
function was assessed in 10 healthy male subjects (age: 26 +/- 3; height: 185 +/-
7 cm; weight: 82 +/- 10 kg; BMI: 24 +/- 3 kg/m2; means +/- SD) using 5-s trials
of neck pressure (+45, +30, and +15 Torr) and neck suction (-20, -40, -60, and
80 Torr) during normothermia (NT) and passive WBH (Delta core temp ~1 degrees C).
Analyses of stimulus response curves (four-parameter logistic model) for CBR
control of heart rate (CBR-HR) and mean arterial pressure (CBR-MAP), as well as
separate two-way ANOVA of the hypotensive and hypertensive stimuli (factor 1:
thermal condition, factor 2: chamber pressure), were performed. For CBR-HR,
maximal gain was increased during WBH (-0.73 +/- 0.11) compared with NT (-0.39 +/
0.04, mean +/- SE, P = 0.03). In addition, the CBR-HR responding range was
increased during WBH (33 +/- 5) compared with NT (19 +/- 2 bpm, P = 0.03).
Separate analysis of hypertensive stimulation revealed enhanced HR responses
during WBH at -40, -60, and -80 Torr (condition * chamber pressure interaction, P
= 0.049) compared with NT. For CBR-MAP, both logistic analysis and separate two
way ANOVA revealed no differences during WBH. Therefore, in response to passive
WBH, CBR control of heart rate (enhanced) and arterial pressure (no change) is
well preserved.
PMID- 27488887
TI - Testosterone therapy in men with testosterone deficiency: are the benefits and
cardiovascular risks real or imagined?
AB - In the adult male, testosterone (T) deficiency (TD) also known as male
hypogonadism, is a well-established medical condition, which has been recognized
for more than a century. T therapy in men with TD was introduced as early as
1940s and was reported to improve overall health with no concomitant serious
adverse effects. A wealth of recent studies demonstrated that T therapy in men
with TD is associated with increased lean body mass, reduced fat mass and waist
circumference, improvement in glycemic control, and reduced obesity. T therapy is
also associated with improvements in lipid profiles, amelioration of metabolic
syndrome (Met S) components, reduced inflammatory biomarkers, reduced systolic
and diastolic blood pressure, and improvements in sexual function. More
importantly, T therapy is associated with amelioration of diabetes and reduced
mortality. However, few studies, marred with serious methodological and
analytical flaws reported between 2010 and 2014, suggested that T therapy is
associated with increased cardiovascular (CV) risk. As summarized in this review,
a thorough and critical analysis of these studies showed that the risks purported
are unsubstantiated and such studies lacked credible scientific and clinical
evidence. Moreover, recent observational, registry studies, clinical trials, and
meta-analyses, all revealed no increase in CV risks in men receiving T therapy.
In this review, the benefits of T therapy in adult men with TD and the lack of
credible evidence suggesting that T therapy is linked to increased CV risks are
discussed. It should be noted that the literature is replete with studies
demonstrating beneficial effects of T therapy on CV and overall health.
PMID- 27488888
TI - Sex differences in the cardiovascular consequences of the inspiratory muscle
metaboreflex.
AB - It is currently unknown whether sex differences exist in the cardiovascular
consequences of the inspiratory muscle metaboreflex. We hypothesized that the
activation of the inspiratory muscle metaboreflex will lead to less of an
increase in mean arterial pressure (MAP) and limb vascular resistance (LVR) and
less of a decrease in limb blood flow (QL) in women compared with men. Twenty
healthy men (n = 10, 23 +/- 2 yr) and women (n = 10, 22 +/- 3 yr) were recruited
for this study. Subjects performed inspiratory resistive breathing tasks (IRBTs)
at 2% or 65% of their maximal inspiratory mouth pressure (PIMAX). During the
IRBTs, the breathing frequency was 20 breaths/min with a 50% duty cycle. At rest
and during the IRBTs, MAP was measured via automated oscillometry, QL was
measured via Doppler ultrasound, and LVR was calculated. EMG was recorded on the
leg to ensure no muscle contraction occurred. The 65% IRBT led to attenuated
increases (P < 0.01) from baseline in women compared with men for MAP (W: 7.3 +/-
2.0 mmHg; M: 11.1 +/- 5.0 mmHg) and LVR (W: 17.7% +/- 14.0%; M: 47.9 +/- 21.0%),
as well as less of a decrease (P < 0.01) in QL (W: -7.5 +/- 9.9%; M: -23.3 +/-
10.2%). These sex differences in MAP, QL, and LVR were still present in a subset
of subjects matched for PIMAX The 2% IRBT resulted in no significant changes in
MAP, QL, or LVR across time or between men and women. These data indicate
premenopausal women exhibit an attenuated inspiratory muscle metaboreflex
compared with age-matched men.
PMID- 27488889
TI - Dietary thylakoids reduce visceral fat mass and increase expression of genes
involved in intestinal fatty acid oxidation in high-fat fed rats.
AB - Thylakoids reduce body weight gain and body fat accumulation in rodents. This
study investigated whether an enhanced oxidation of dietary fat-derived fatty
acids in the intestine contributes to the thylakoid effects. Male Sprague-Dawley
rats were fed a high-fat diet with (n = 8) or without thylakoids (n = 8) for 2
wk. Body weight, food intake, and body fat were measured, and intestinal mucosa
was collected and analyzed. Quantitative real-time PCR was used to measure gene
expression levels of key enzymes involved in fatty acid transport, fatty acid
oxidation, and ketogenesis. Another set of thylakoid-treated (n = 10) and control
rats (n = 10) went through indirect calorimetry. In the first experiment,
thylakoid-treated rats (n = 8) accumulated 25% less visceral fat than controls.
Furthermore, fatty acid translocase (Fat/Cd36), carnitine palmitoyltransferase 1a
(Cpt1a), and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2)
genes were upregulated in the jejunum of the thylakoid-treated group. In the
second experiment, thylakoid-treated rats (n = 10) gained 17.5% less weight
compared with controls and their respiratory quotient was lower, 0.86 compared
with 0.91. Thylakoid-intake resulted in decreased food intake and did not cause
steatorrhea. These results suggest that thylakoids stimulated intestinal fatty
acid oxidation and ketogenesis, resulting in an increased ability of the
intestine to handle dietary fat. The increased fatty acid oxidation and the
resulting reduction in food intake may contribute to the reduced fat accumulation
in thylakoid-treated animals.
PMID- 27488890
TI - Deletion of soluble epoxide hydrolase enhances coronary reactive hyperemia in
isolated mouse heart: role of oxylipins and PPARgamma.
AB - The relationship between soluble epoxide hydrolase (sEH) and coronary reactive
hyperemia (CRH) response to a brief ischemic insult is not known.
Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects in
ischemia/reperfusion injury. sEH converts EETs into dihydroxyeicosatrienoic-acids
(DHETs). Therefore, we hypothesized that knocking out sEH enhances CRH through
modulation of oxylipin profiles, including an increase in EET/DHET ratio.
Compared with sEH+/+, sEH-/- mice showed enhanced CRH, including greater
repayment volume (RV; 28% higher, P < 0.001) and repayment/debt ratio (32%
higher, P < 0.001). Oxylipins from the heart perfusates were analyzed by LC
MS/MS. The 14,15-EET/14,15-DHET ratio was 3.7-fold higher at baseline (P < 0.001)
and 5.6-fold higher post-ischemia (P < 0.001) in sEH-/- compared with sEH+/+
mice. Likewise, the baseline 9,10- and 12,13-EpOME/DiHOME ratios were 3.2-fold (P
< 0.01) and 3.7-fold (P < 0.001) higher, respectively in sEH-/- compared with
sEH+/+ mice. 13-HODE was also significantly increased at baseline by 71% (P <
0.01) in sEH-/- vs. sEH+/+ mice. Levels of 5-, 11-, 12-, and 15
hydroxyeicosatetraenoic acids were not significantly different between the two
strains (P > 0.05), but were decreased postischemia in both groups (P = 0.02, P =
0.04, P = 0.05, P = 0.03, respectively). Modulation of CRH by peroxisome
proliferator-activated receptor gamma (PPARgamma) was demonstrated using a
PPARgamma-antagonist (T0070907), which reduced repayment volume by 25% in sEH+/+
(P < 0.001) and 33% in sEH-/- mice (P < 0.01), and a PPARgamma-agonist
(rosiglitazone), which increased repayment volume by 37% in both sEH+/+ (P =
0.04) and sEH-/- mice (P = 0.04). l-NAME attenuated CRH in both sEH-/- and sEH+/+
These data demonstrate that genetic deletion of sEH resulted in an altered
oxylipin profile, which may have led to an enhanced CRH response.
PMID- 27488891
TI - Diffusive shunting of gases and other molecules in the renal vasculature:
physiological and evolutionary significance.
AB - Countercurrent systems have evolved in a variety of biological systems that allow
transfer of heat, gases, and solutes. For example, in the renal medulla, the
countercurrent arrangement of vascular and tubular elements facilitates the
trapping of urea and other solutes in the inner medulla, which in turn enables
the formation of concentrated urine. Arteries and veins in the cortex are also
arranged in a countercurrent fashion, as are descending and ascending vasa recta
in the medulla. For countercurrent diffusion to occur, barriers to diffusion must
be small. This appears to be characteristic of larger vessels in the renal
cortex. There must also be gradients in the concentration of molecules between
afferent and efferent vessels, with the transport of molecules possible in either
direction. Such gradients exist for oxygen in both the cortex and medulla, but
there is little evidence that large gradients exist for other molecules such as
carbon dioxide, nitric oxide, superoxide, hydrogen sulfide, and ammonia. There is
some experimental evidence for arterial-to-venous (AV) oxygen shunting.
Mathematical models also provide evidence for oxygen shunting in both the cortex
and medulla. However, the quantitative significance of AV oxygen shunting remains
a matter of controversy. Thus, whereas the countercurrent arrangement of vasa
recta in the medulla appears to have evolved as a consequence of the evolution of
Henle's loop, the evolutionary significance of the intimate countercurrent
arrangement of blood vessels in the renal cortex remains an enigma.
PMID- 27488892
TI - Hydrogen sulfide as a regulator of respiratory epithelial sodium transport: the
role of sodium-potassium ATPase. Focus on "Hydrogen sulfide contributes to
hypoxic inhibition of airway transepithelial sodium absorption".
PMID- 27488893
TI - Moving the needle: Optimizing classification for glioma.
AB - Genomic markers provide unbiased information that is increasingly being used to
enhance traditional histopathology approaches for classification of cancer
samples.
PMID- 27488894
TI - Comment on "Cancer chemoprevention: Evidence of a nonlinear dose response for the
protective effects of resveratrol in humans and mice".
AB - In Apc(Min) mice (an animal model of colorectal carcinogenesis) fed a high-fat
diet, low doses of resveratrol suppress intestinal adenoma development more
potently than high doses do; however, these findings appear affected by multiple
confounding factors, as resveratrol alone added to a standard diet has opposite
outcomes.
PMID- 27488895
TI - Response to comment on "Cancer chemoprevention: Evidence of a nonlinear dose
response for the protective effects of resveratrol in humans and mice".
AB - Low-dose resveratrol did not have the opposite effect on intestinal adenoma
development when given in a standard diet instead of a high-fat diet, although we
agree on the need for more information on the interaction of diet-derived
compounds such as resveratrol and other lifestyle, metabolic and hormonal
factors.
PMID- 27488896
TI - Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy
outcomes in cervical cerclage.
AB - Preterm birth, the leading cause of death in children under 5 years, may be
caused by inflammation triggered by ascending vaginal infection. About 2 million
cervical cerclages are performed annually to prevent preterm birth. The procedure
is thought to provide structural support and maintain the endocervical mucus plug
as a barrier to ascending infection. Two types of suture material are used for
cerclage: monofilament or multifilament braided. Braided sutures are most
frequently used, although no evidence exists to favor them over monofilament
sutures. We assessed birth outcomes in a retrospective cohort of 678 women
receiving cervical cerclage in five UK university hospitals and showed that
braided cerclage was associated with increased intrauterine death (15% versus 5%;
P = 0.0001) and preterm birth (28% versus 17%; P = 0.0006) compared to
monofilament suture. To understand the potential underlying mechanism, we
performed a prospective, longitudinal study of the vaginal microbiome in women at
risk of preterm birth because of short cervical length (<=25 mm) who received
braided (n = 25) or monofilament (n = 24) cerclage under comparable
circumstances. Braided suture induced a persistent shift toward vaginal
microbiome dysbiosis characterized by reduced Lactobacillus spp. and enrichment
of pathobionts. Vaginal dysbiosis was associated with inflammatory cytokine and
interstitial collagenase excretion into cervicovaginal fluid and premature
cervical remodeling. Monofilament suture had comparatively minimal impact upon
the vaginal microbiome and its interactions with the host. These data provide in
vivo evidence that a dynamic shift of the human vaginal microbiome toward
dysbiosis correlates with preterm birth.
PMID- 27488897
TI - The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm
dysfunction.
AB - Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm
function in response to mechanical ventilation, which has negative consequences
for individual patients' quality of life and for the health care system, but
specific treatment strategies are still lacking. We used an experimental
intensive care unit (ICU) model, allowing time-resolved studies of diaphragm
structure and function in response to long-term mechanical ventilation and the
effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The
marked loss of diaphragm muscle fiber function in response to mechanical
ventilation was caused by posttranslational modifications (PTMs) of myosin. In a
rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber
function (by about 100%), although it did not reverse diaphragm atrophy. The
treatment also provided protection from myosin PTMs associated with HSP72
induction and PARP-1 inhibition, resulting in improvement of mitochondrial
function and content. Thus, BGP-15 may offer an intervention strategy for
reducing VIDD in mechanically ventilated ICU patients.
PMID- 27488898
TI - Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low
CEBPalpha expression.
AB - Lung cancer is the most common cause of cancer deaths. The expression of the
transcription factor C/EBPalpha (CCAAT/enhancer binding protein alpha) is
frequently lost in non-small cell lung cancer, but the mechanisms by which
C/EBPalpha suppresses tumor formation are not fully understood. In addition, no
pharmacological therapy is available to specifically target C/EBPalpha
expression. We discovered a subset of pulmonary adenocarcinoma patients in whom
negative/low C/EBPalpha expression and positive expression of the oncogenic
protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic
value. We also generated a lung-specific mouse model of C/EBPalpha deletion that
develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency.
BMI1 activity is required for both tumor initiation and maintenance in the
C/EBPalpha-null background, and pharmacological inhibition of BMI1 exhibits
antitumor effects in both murine and human adenocarcinoma lines. Overall, we show
that C/EBPalpha is a tumor suppressor in lung cancer and that BMI1 is required
for the oncogenic process downstream of C/EBPalpha loss. Therefore, anti-BMI1
pharmacological inhibition may offer a therapeutic benefit for lung cancer
patients with low expression of C/EBPalpha and high BMI1.
PMID- 27488899
TI - Phosphatidylserine Converts Immunogenic Recombinant Human Acid Alpha-Glucosidase
to a Tolerogenic Form in a Mouse Model of Pompe Disease.
AB - Development of unwanted immune responses against therapeutic proteins is a major
clinical complication. Recently, we have shown that exposure of Factor VIII in
the presence of phosphatidylserine (PS) induces antigen-specific
hyporesponsiveness to Factor VIII rechallenge, suggesting that PS is not immune
suppressive, but rather immune regulatory in that PS converts an immunogen to a
tolerogen. Since PS is exposed in the outer leaflet during apoptosis, we
hypothesize that PS imparts tolerogenic activity to this natural process. Thus,
immunization with PS containing liposomes would mimic this natural process. Here,
we investigate the immune regulatory effects of PS in inducing tolerance toward
recombinant human acid alpha-glucosidase (rhGAA). rhGAA was found to complex with
PS liposomes through hydrophobic interactions, and incubation PS-rhGAA with
dendritic cells resulted in the increased secretion of transforming growth factor
beta. Immunization with PS-rhGAA or O-phospho-L-serine-rhGAA led to a reduction
in anti-rhGAA antibody response which persisted despite rechallenge with free
rhGAA. Importantly, the titer levels in a majority of these animals remained
unchanged after rechallenge and can be considered nonresponders. These data
provide evidence that PS liposomes can be used to induce tolerance toward
therapeutic proteins, in general.
PMID- 27488900
TI - Cholesterol-Targeted Anticancer and Apoptotic Effects of Anionic and Polycationic
Amphiphilic Cyclodextrin Nanoparticles.
AB - Amphiphilic cyclodextrins (CDs) are biocompatible derivatives of natural CDs and
are able to form nanoparticles or polyplexes spontaneously. In this study,
nanoparticles prepared from nonionic (6OCaprobetaCD) or cationic amphiphilic CD
(PC betaCDC6) were used comparatively to develop nanoparticles intended for
breast cancer therapy. The characterization of these nanoparticles was performed
both by in vitro and cell culture studies. Furthermore, the apoptotic and
cytotoxic effects of blank amphiphilic CDs were demonstrated by various
mechanistic methods including Caspase-8 activity, lipid peroxidation assay, TUNEL
assay, Tali((r))-based image analysis, cholesterol assay, and gene expression
studies. Blank nanoparticles exerted cytotoxicity against a variety of cancer
cells (MCF-7, HeLa, HepG2, and MB49) but none to healthy cells (L929, G/G).
Interestingly, blank 6OCaprobetaCD and blank PC betaCDC6 derivatives were found
to be intrinsically effective on cell number and membrane integrity of MCF-7
cells in apoptosis studies. Further in-depth studies were performed to elucidate
the selective mechanism of anticancer action in MCF-7 cells caused by these
amphiphilic CDs. In conclusion, blank amphiphilic CD nanoparticles induced
apoptosis through mitochondrial pathway targeted to cholesterol microdomains in
cancer cell membrane.
PMID- 27488901
TI - Particle Formation and Aggregation of a Therapeutic Protein in Nanobubble
Suspensions.
AB - The generation of nanobubbles following reconstitution of lyophilized trehalose
formulations has recently been reported. Here, we characterize particle formation
and aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra)
in reconstituted formulations of lyophilized trehalose. Particle characterization
methods including resonant mass measurement and nanoparticle tracking analysis
were used to count and size particles generated upon reconstitution of
lyophilized trehalose formulations. In addition, accelerated degradation studies
were conducted to monitor rhIL-1ra aggregation in solutions containing various
concentrations of suspended nanobubbles. Reconstitution of lyophilized trehalose
formulations with solutions containing rhIL-1ra reduced nanobubble concentrations
and generated negatively buoyant particles attributed to aggregated rhIL-1ra.
Furthermore, levels of rhIL-1ra aggregation following incubation in aqueous
solution correlated with concentrations of suspended nanobubbles. The results of
this study suggest that nanobubbles may be a contributor to protein aggregation
and particle formation in reconstituted, lyophilized therapeutic protein
formulations.
PMID- 27488902
TI - Studying the Propensity of Compounds to Supersaturate: A Practical and Broadly
Applicable Approach.
AB - Supersaturating drug delivery systems can enhance the oral bioavailability of
poorly soluble drug compounds. Supersaturation of such compounds has been studied
in many different ways; however, a more standardized method is required. The
rationale of choosing suitable concentrations of supersaturation to study has
previously been very inconsistent. This makes comparisons between studies and
compounds difficult, as the propensity of compounds to supersaturate varies
greatly. This study presents a standardized method to study the supersaturation
of drug compounds. The method allows, both, for a ranking of compounds according
to their supersaturation propensity and the effectiveness of precipitation
inhibitors. The time-concentration profile of supersaturation and precipitation
was studied in situ for 4 different concentrations for 6 model compounds
(albendazole, aprepitant, danazol, felodipine, fenofibrate, and tadalafil) in the
MUDISS ProfilerTM in fasted-state simulated intestinal fluid. A relation between
the induction time of nucleation and the initial supersaturated concentration
could be established based on classical nucleation theory. The model compounds
had different propensities to upersaturate. The data show that a single degree of
supersaturation or concentration would not have described the different systems
adequately. The method could be used in early preformulation for characterization
of supersaturation propensity of novel compounds or precipitation inhibitor
effects.
PMID- 27488903
TI - Magneto-Optical Activity in High Index Dielectric Nanoantennas.
AB - The magneto-optical activity, namely the polarization conversion capabilities of
high-index, non-absorbing, core-shell dielectric nanospheres is theoretically
analyzed. We show that, in analogy with their plasmonic counterparts, the
polarization conversion in resonant dielectric particles is linked to the amount
of electromagnetic field probing the magneto-optical material in the system.
However, in strong contrast with plasmon nanoparticles, due to the peculiar
distribution of the internal fields in resonant dielectric spheres, the magneto
optical response is fully governed by the magnetic (dipolar and quadrupolar)
resonances with little effect of the electric ones.
PMID- 27488904
TI - PACSIN1 regulates the dynamics of AMPA receptor trafficking.
AB - Dynamic trafficking of AMPA receptors (AMPARs) into and out of synapses plays an
important role in synaptic plasticity. We previously reported that the protein
kinase C and casein kinase II substrate in neurons (PACSIN) forms a complex with
AMPARs through its interaction with the protein interacting with C-kinase 1
(PICK1) to regulate NMDA receptor (NMDAR)-induced AMPAR endocytosis and
cerebellar long-term depression. However, the molecular mechanism by which PACSIN
regulates the dynamics of AMPAR trafficking remains unclear. Using a pH-sensitive
green fluorescent protein, pHluorin, tagged to the extracellular domain of the
GluA2 subunit of AMPARs, we demonstrate dual roles for PACSIN1 in controlling the
internalization and recycling of GluA2 after NMDAR activation. Structure and
function analysis reveals a requirement for the PACSIN1 F-BAR and SH3 domains in
controlling these NMDAR-dependent processes. Interestingly, the variable region,
which binds to PICK1, is not essential for NMDAR-dependent GluA2 internalization
and is required only for the correct recycling of AMPARs. These results indicate
that PACSIN is a versatile membrane deformation protein that links the endocytic
and recycling machineries essential for dynamic AMPAR trafficking in neurons.
PMID- 27488906
TI - Rule 27 of the International Code of Nomenclature of prokaryotes: the basonym is
not enough.
AB - Proposals to make changes to the wording of Rule 27 of the International Code of
Nomenclature of Prokaryotes have been made that include the requirement to make
reference to the basonym of a new combination. While this is a step in the right
direction, it does not solve problems where new combinations are associated with
multiple heterotypic synonyms and the new combination is based on the selection
of the genus name or species epithet that is contrary to the Rules.
PMID- 27488905
TI - Advanced breast cancer clinical nursing curriculum: review and recommendations.
AB - PURPOSE: The needs and concerns of patients with advanced breast cancer are
changing at every phase of the care intervention. Management and coordination of
hospital resources and services are also steadily evolving. The objective of the
present expert report is to define a new oncology nursing role specialising in
advanced breast cancer, to help guide patients throughout the whole healthcare
itinerary. METHODS: A group of eight experts in oncology nursing and medical
oncology defined the content index of the curriculum document. A systematic
review of bibliography was carried out, and the relevant contents were extracted.
Based on these contents and the participants' experience, recommendations were
formulated and validated through a Delphi questionnaire and a participative
meeting. RESULTS: The advanced breast cancer clinical nurse (ABCCN) should
develop a clinical, psychosocial role focused on coordinating patients in the
healthcare network. The nurse would be in charge of evaluating and supervising
the care administered and the healthcare resources used. The ABCCN should be
aware and participate in the protocols and available resources, be able to solve
conflicts, deal with burn-out signs and have clinical, coaching and team-working
abilities. The proposed curriculum provides a specific process for the care of
patients, as well as an implementation process. CONCLUSIONS: The ABCCN's role is
crucial to assume the best care and the optimisation of available resources. This
review and consensus document provides the required tools for the implementation
in hospitals.
PMID- 27488907
TI - Detection of kobuvirus RNA in Japanese domestic dogs.
AB - To investigate whether kokuvirus is present in Japanese dogs, we examined the
fecal samples obtained from 94 diarrheal household dogs and 50 clinically healthy
kenneled dogs by RT-PCR. The gene was detected in 37.2% and 48.0% in the former
and the latter, respectively, suggesting that canine kobuvirus (CaKoV) is
circulating among Japanese dogs. From the result of the latter, however, CaKoV
may not be a primary pathogen. Furthermore, all gene-positive dogs were purebreds
aged four months or younger. This finding suggests that CaKoV endemic is confined
in multi-dog environments, and the dogs have a strong age-dependent resistance to
CaKoV.
PMID- 27488908
TI - Intracranial stenosis in cognitive impairment and dementia.
AB - Intracranial stenosis is a common vascular lesion observed in Asian and other non
Caucasian stroke populations. However, its role in cognitive impairment and
dementia has been under-studied. We, therefore, examined the association of
intracranial stenosis with cognitive impairment, dementia and their subtypes in a
memory clinic case-control study, where all subjects underwent detailed
neuropsychological assessment and 3 T neuroimaging including three-dimensional
time-of-flight magnetic resonance angiography. Intracranial stenosis was defined
as >=50% narrowing in any of the intracranial arteries. A total of 424 subjects
were recruited of whom 97 were classified as no cognitive impairment, 107 as
cognitive impairment no dementia, 70 vascular cognitive impairment no dementia,
121 Alzheimer's Disease, and 30 vascular dementia. Intracranial stenosis was
associated with dementia (age/gender/education - adjusted odds ratios (OR): 4.73,
95% confidence interval (CI): 1.93-11.60) and vascular cognitive impairment no
dementia (OR: 3.98, 95% CI: 1.59-9.93). These associations were independent of
cardiovascular risk factors and MRI markers. However, the association with
Alzheimer's Disease and vascular dementia became attenuated in the presence of
white matter hyperintensities. Intracranial stenosis is associated with vascular
cognitive impairment no dementia independent of MRI markers. In Alzheimer's
Disease and vascular dementia, this association is mediated by cerebrovascular
disease. Future studies focusing on perfusion and functional markers are needed
to determine the pathophysiological mechanism(s) linking intracranial stenosis
and cognition so as to identify treatment strategies.
PMID- 27488909
TI - Insulin resistance is associated with lower arterial blood flow and reduced
cortical perfusion in cognitively asymptomatic middle-aged adults.
AB - Insulin resistance (IR) is associated with poor cerebrovascular health and
increased risk for dementia. Little is known about the unique effect of IR on
both micro- and macrovascular flow particularly in midlife when interventions
against dementia may be most effective. We examined the effect of IR as indexed
by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral
blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI)
among cognitively asymptomatic middle-aged individuals. We hypothesized that
higher HOMA-IR would be associated with reduced flow in macrovessels and lower
cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged
adults (57 +/- 5 yrs) underwent fasting blood draw, phase contrast-vastly
undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin
labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood
flow, particularly within the internal carotid arteries (ICAs), and lower
cerebral perfusion in several brain regions including frontal and temporal lobe
regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion
in individuals with lower HOMA-IR, a relationship not observed among those with
higher HOMA-IR. Findings provide novel evidence for an uncoupling of
macrovascular blood flow and microvascular perfusion among individuals with
higher IR in midlife.
PMID- 27488910
TI - Diphenhydramine as a selective probe to study H+-antiporter function at the blood
brain barrier: Application to [11C]diphenhydramine positron emission tomography
imaging.
AB - Diphenhydramine, a sedative histamine H1-receptor (H1R) antagonist, was evaluated
as a probe to measure drug/H+-antiporter function at the blood-brain barrier. In
situ brain perfusion experiments in mice and rats showed that diphenhydramine
transport at the blood-brain barrier was saturable, following Michaelis-Menten
kinetics with a Km = 2.99 mM and Vmax = 179.5 nmol s-1 g-1. In the
pharmacological plasma concentration range the carrier-mediated component
accounted for 77% of diphenhydramine influx while passive diffusion accounted for
only 23%. [14C]Diphenhydramine blood-brain barrier transport was proton and
clonidine sensitive but was influenced by neither tetraethylammonium, a MATE1
(SLC47A1), and OCT/OCTN (SLC22A1-5) modulator, nor P-gp/Bcrp (ABCB1a/1b/ABCG2)
deficiency. Brain and plasma kinetics of [11C]diphenhydramine were measured by
positron emission tomography imaging in rats. [11C]Diphenhydramine kinetics in
different brain regions were not influenced by displacement with 1 mg kg-1
unlabeled diphenhydramine, indicating the specificity of the brain positron
emission tomography signal for blood-brain barrier transport activity over
binding to any central nervous system target in vivo. [11C]Diphenhydramine
radiometabolites were not detected in the brain 15 min after injection, allowing
for the reliable calculation of [11C]diphenhydramine brain uptake clearance (Clup
= 0.99 +/- 0.18 mL min-1 cm-3). Diphenhydramine is a selective and specific H+
antiporter substrate. [11C]Diphenhydramine positron emission tomography imaging
offers a reliable and noninvasive method to evaluate H+-antiporter function at
the blood-brain barrier.
PMID- 27488911
TI - An automated method measures variability in P-glycoprotein and ABCG2 densities
across brain regions and brain matter.
AB - Changes in P-glycoprotein and ABCG2 densities may play a role in amyloid-beta
accumulation in Alzheimer's disease. However, previous studies report conflicting
results from different brain regions, without correcting for changes in vessel
density. We developed an automated method to measure transporter density
exclusively within the vascular space, thereby correcting for vessel density. We
then examined variability in transporter density across brain regions, matter,
and disease using two cohorts of post-mortem brains from Alzheimer's disease
patients and age-matched controls. Changes in transporter density were also
investigated in capillaries near plaques and on the mRNA level. P-glycoprotein
density varied with brain region and matter, whereas ABCG2 density varied with
brain matter. In temporal cortex, P-glycoprotein density was 53% lower in
Alzheimer's disease samples than in controls, and was reduced by 35% in
capillaries near plaque deposits within Alzheimer's disease samples. ABCG2
density was unaffected in Alzheimer's disease. No differences were detected at
the transcript level. Our study indicates that region-specific changes in
transporter densities can occur globally and locally near amyloid-beta deposits
in Alzheimer's disease, providing an explanation for conflicting results in the
literature. When differences in region and matter are accounted for, changes in
density can be reproducibly measured using our automated method.
PMID- 27488912
TI - Four years of corneal keratoplasty in Italian paediatric patients: indications
and clinical outcomes.
AB - PURPOSE: The purpose was to evaluate indications and clinical outcomes in
paediatric corneal keratoplasty. METHODS: Fifty-four eyes of 43 patients who
underwent corneal keratoplasty from the 1st of January 2010 through the 31st of
December 2013 at the Bambino Gesu Children's Hospital in Rome, Italy, were
retrospectively evaluated. To assess the effect of age on graft failure rate, the
recipient age was considered as a dichotomous variable (<=5 or >5 years) and a
2X2 table was developed, using the chi-square test for testing the statistical
significance. Furthermore, two separate subgroup analyses were conducted on
patients of <=5 years and those of >5 years, to evaluate the effect of
penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty (DALK) on
the graft failure rate. The level of statistical significance was set at p < 0.05
RESULTS: Mean recipient age was 8.9 +/- 5.7 [SD] years. Mean follow-up time was
22.8 months. Main preoperative diagnoses were keratoconus (37 %) and congenital
glaucoma (20 %). Patients <=5 years showed a higher percentage of graft failure
(p = 0.0008). PK and DALK did not show statistically significant differences
regarding the graft failure in both subgroups (p = 0.15 for <=5 years group and p
= 0.27 for >5 years group, respectively). However, across groups DALK provided a
lower rate of graft failure. CONCLUSIONS: Our findings suggest that children
older than 5 years show a significantly better graft outcome and that DALK seems
to offer greatest benefits in terms of failure risk in paediatric patients.
PMID- 27488914
TI - Relationship Between Intrinsic Motivation and Undergraduate Students' Depression
and Stress: The Moderating Effect of Interpersonal Conflict.
AB - This study examined the effect of intrinsic academic motivation and interpersonal
conflict on the perceived depression and stress. Participants were 537 Chinese
undergraduate students (191 males and 346 females; M age = 20.4 years, SD age =
1.3). They completed four scales measuring intrinsic academic motivation,
interpersonal conflict, stress, and depression. Linear regressions were conducted
with intrinsic academic motivation, interpersonal conflict, and their interaction
as independent variables to predict depression and stress. Results showed that
intrinsic academic motivation was negatively, while interpersonal conflict was
positively, associated with depression and stress. Moreover, the interaction was
significant: negative association of "intrinsic academic motivation and
depression" and that of "intrinsic academic motivation and stress" was weaker
among participants who reported higher (vs. lower) levels of interpersonal
conflict.
PMID- 27488913
TI - Severity of clinical presentation in youth with type 1 diabetes is associated
with differences in brain structure.
AB - OBJECTIVE: Differences in cognition and brain structure have been found in youth
with type 1 diabetes compared with controls, even after relatively short disease
duration. To determine whether severity of clinical presentation contributes to
these differences, we obtained structural magnetic resonance imaging (MRI) scans
in youth ages 7-17 who were either newly diagnosed with type 1 diabetes (<3.5
months from diagnosis, n = 46) or a sibling without diabetes (n = 28). RESEARCH
DESIGN AND METHODS: Severity of presentation was measured by the presence of
diabetic ketoacidosis (DKA) and degree of hyperglycemia exposure [hemoglobin A1c
(HbA1c)] at diagnosis. MRI were obtained using T1-weighted, T2-weighted, and
diffusion-weighted sequences. RESULTS: Within the group with type 1 diabetes, 12
subjects presented in DKA and 34 did not. After controlling for age, sex, and
multiple comparisons, the type 1 diabetes group had lower volume in the left
temporal-parietal-occipital cortex compared with controls. Within the type 1
diabetes group, DKA at presentation was associated with lower radial, axial, and
mean diffusivity (MD) throughout major white matter tracts and higher HbA1c was
associated with lower hippocampal, thalamic, and cerebellar white matter volumes,
lower right posterior parietal cortical thickness, and greater right occipital
cortical thickness. CONCLUSION: These data suggest that severity of clinical
presentation is an important factor in predicting brain structural differences in
youth with type 1 diabetes approximately 3 months after diagnosis.
PMID- 27488915
TI - Characterisation of atopic dermatitis (AD) endotypes and novel treatment targets:
towards a molecular classification.
PMID- 27488916
TI - Saving antibiotics for when they are really needed: the Dutch example.
PMID- 27488917
TI - Epidemiology and economic burden of measles, mumps, pertussis, and varicella in
Germany: a systematic review.
AB - OBJECTIVES: Despite the availability of vaccines and the existence of public
vaccination recommendations, outbreaks of vaccine-preventable childhood diseases
still cause public health debate. The objective of this systematic review was to
provide an overview of the current epidemiology and economic burden of measles,
mumps, pertussis, and varicella in Germany. METHODS: We systematically reviewed
studies published since 2000. The literature search was conducted using PubMed
and EMBASE. Also, we used German notification data to give an up-to-date overview
of the epidemiology of the four diseases under consideration. RESULTS: Thirty-six
studies were included in our review. Results suggest that there is still
considerable morbidity due to childhood diseases in Germany. Studies providing
cost estimates are scarce. Comparative analyses of different data sources
(notification data vs. claims data) revealed a potential underestimation of
incidence estimates when using notification data. Furthermore, several studies
showed regional differences in incidence of some of the diseases under
consideration. CONCLUSIONS: Our findings underline the need for improved
vaccination and communication strategies targeting all susceptible age and risk
groups on a national and local level.
PMID- 27488918
TI - Molecular Properties of Drugs Interacting with SLC22 Transporters OAT1, OAT3,
OCT1, and OCT2: A Machine-Learning Approach.
AB - Statistical analysis was performed on physicochemical descriptors of ~250 drugs
known to interact with one or more SLC22 "drug" transporters (i.e., SLC22A6 or
OAT1, SLC22A8 or OAT3, SLC22A1 or OCT1, and SLC22A2 or OCT2), followed by
application of machine-learning methods and wet laboratory testing of novel
predictions. In addition to molecular charge, organic anion transporters (OATs)
were found to prefer interacting with planar structures, whereas organic cation
transporters (OCTs) interact with more three-dimensional structures (i.e.,
greater SP3 character). Moreover, compared with OAT1 ligands, OAT3 ligands
possess more acyclic tetravalent bonds and have a more zwitterionic/cationic
character. In contrast, OCT1 and OCT2 ligands were not clearly distinquishable
form one another by the methods employed. Multiple pharmacophore models were
generated on the basis of the drugs and, consistent with the machine-learning
analyses, one unique pharmacophore created from ligands of OAT3 possessed
cationic properties similar to OCT ligands; this was confirmed by quantitative
atomic property field analysis. Virtual screening with this pharmacophore,
followed by transport assays, identified several cationic drugs that selectively
interact with OAT3 but not OAT1. Although the present analysis may be somewhat
limited by the need to rely largely on inhibition data for modeling, wet
laboratory/in vitro transport studies, as well as analysis of drug/metabolite
handling in Oat and Oct knockout animals, support the general validity of the
approach-which can also be applied to other SLC and ATP binding cassette drug
transporters. This may make it possible to predict the molecular properties of a
drug or metabolite necessary for interaction with the transporter(s), thereby
enabling better prediction of drug-drug interactions and drug-metabolite
interactions. Furthermore, understanding the overlapping specificities of OATs
and OCTs in the context of dynamic transporter tissue expression patterns should
help predict net flux in a particular tissue of anionic, cationic, and
zwitterionic molecules in normal and pathophysiological states.
PMID- 27488920
TI - Parametric recursive system identification and self-adaptive modeling of the
human energy metabolism for adaptive control of fat weight.
AB - A mathematical model has been developed to facilitate indirect measurements of
difficult to measure variables of the human energy metabolism on a daily basis.
The model performs recursive system identification of the parameters of the
metabolic model of the human energy metabolism using the law of conservation of
energy and principle of indirect calorimetry. Self-adaptive models of the
utilized energy intake prediction, macronutrient oxidation rates, and daily body
composition changes were created utilizing Kalman filter and the nominal
trajectory methods. The accuracy of the models was tested in a simulation study
utilizing data from the Minnesota starvation and overfeeding study. With biweekly
macronutrient intake measurements, the average prediction error of the utilized
carbohydrate intake was -23.2 +/- 53.8 kcal/day, fat intake was 11.0 +/- 72.3
kcal/day, and protein was 3.7 +/- 16.3 kcal/day. The fat and fat-free mass
changes were estimated with an error of 0.44 +/- 1.16 g/day for fat and -2.6 +/-
64.98 g/day for fat-free mass. The daily metabolized macronutrient energy intake
and/or daily macronutrient oxidation rate and the daily body composition change
from directly measured serial data are optimally predicted with a self-adaptive
model with Kalman filter that uses recursive system identification.
PMID- 27488919
TI - Development of Poly Unsaturated Fatty Acid Derivatives of Aspirin for Inhibition
of Platelet Function.
AB - The inhibition of platelet aggregation is key to preventing conditions such as
myocardial infarction and ischemic stroke. Aspirin is the most widely used drug
to inhibit platelet aggregation. Aspirin absorption can be improved further to
increase its permeability across biologic membranes via esterification or
converting the carboxylic acid to an anhydride. There are several reports
indicating that omega-3 and omega-6 fatty acids such as linoleic acid,
eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) separately inhibit
platelet aggregation. Herein, we synthesize anhydride conjugates of aspirin with
linoleic acid, EPA, and DHA to form aspirin anhydrides that are expected to have
higher permeability across cellular membranes. These aspirin-fatty acid
anhydrides inhibited platelet aggregation in washed human platelets and platelet
rich plasma in a dose-dependent manner. In particular, the aspirin-DHA anhydride
displayed similar effectiveness to aspirin. Platelet aggregation studies
conducted in the presence of various platelet agonists indicated that the aspirin
lipid conjugates act through inhibition of the cyclooxygenase (COX)-thromboxane
synthase (TXAS) pathway. Hence, we performed detailed biochemical studies using
purified COX-1 as well as TXAS stabilized in nanoscale lipid bilayers of
nanodiscs to confirm results from the platelet aggregation studies. We show that
although all of the aspirin conjugates act through the COX-TXAS pathway by
inhibiting COX-1, the parent fatty acids do not act via this pathway. Finally, we
studied the hydrolysis of these compounds in buffer and human plasma, and we
demonstrate that all of the aspirin-fatty acid conjugates hydrolyze to the parent
molecules aspirin and fatty acid in a controlled manner.
PMID- 27488921
TI - The humidifier disinfectant case and the legislative challenges of the 20th
Congress.
AB - A number of absurdities surrounding the humidifier disinfectant (HD) incident may
have occurred because 1) a judicial system operates on the underlying false
assumption that the involved parties are equals in knowledge, information and
resource mobilization capabilities, regardless of respective real status as
company or individual; 2) there is a lack of a system that mandates a company to
prevent and actively manage possible catastrophes; 3) the regulatory scheme makes
companies believe that as long as they are complying with the existing
regulations, they have satisfied all of their responsibilities. I believe that
this issue is an opportunity to bring about changes in the judicial redress
system, the system of internal management of manufacturers, and the regulatory
system of the government. The following regulation amendments are needed to move
towards the changes stated above. First, legislation relating to victim relief
that is applicable to the HD incident must be established. Second, a risk
management system must be formed within the manufacturing company and to this end
an institutional environment for the system must be established within regulatory
framework. Furthermore, legislation must be passed that could punish companies
themselves that have caused severe damage to individuals because they had failed
to take necessary actions to avoid foreseeable harm. Finally, the framework of
regulation must be changed so that the company, who has the necessary information
regarding the product and the component chemicals used in the product, must self
directed experiment and assessment of the safety of their own products.
PMID- 27488925
TI - Expression analysis and promoter methylation under osmotic and salinity stress of
TaGAPC1 in wheat (Triticum aestivum L).
AB - Cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC) catalyzes a key
reaction in glycolysis and encoded by a multi-gene family which showed
instability expression under abiotic stress. DNA methylation is an epigenetic
modification that plays an important role in gene regulation in response to
abiotic stress. The comprehension of DNA methylation at promoter region of
TaGAPC1 can provide insights into the transcription regulation mechanisms of
plant genes under abiotic stress. In this study, we cloned TaGAPC1 genes and its
promoters from two wheat genomes, then investigated the expression patterns of
TaGAPC1 under osmotic and salinity stress, and analyzed the promoter sequences.
Moreover, the methylation patterns of promoters under stress were confirmed.
Expression analysis indicated that TaGAPC1 was induced inordinately by stresses
in two wheat genotypes with contrasting drought tolerance. Several stress-related
cis-acting elements (MBS, DRE, GT1 and LTR et al.) were located in its promoters.
Furthermore, the osmotic and salinity stress induced the demethylation of CG and
CHG nucleotide in the promoter region of Changwu134. The methylation level of CHG
and CHH in promoter of Zhengyin1 was always increased under stresses, and the CG
contexts remained unchanged. The cytosine loci of stress-related cis-acting
elements also showed different methylation changes in this process. These results
provide insights into the relationship between promoter methylation and gene
expression, promoting the function investigation of GAPC.
PMID- 27488926
TI - Folding recombinant spider-silk in H2 O: Effect of osmolytes on the solution
conformation of a 15-repeat spider-silk mimetic.
AB - The folding of a recombinant spider silk protein-polymer in the presence of the
tri-methylamine osmolytes TMANO and Betaine in 80% H2 O is reported. Circular
dichroism measurements (CD) reveal an increase in alpha-helical secondary
structure with increasing osmolyte concentrations, as determined by an increase
in ellipticity at 222 nm. Consistent with this observation, the signal for random
coil sampling, observed at 205 nm, is greatly reduced with increasing
trimethylamine. Fluorescence spectra of a single tyrosine positioned within the
conserved 33-amino acid repeat primary sequence (of the spider-silk mimetic)
complements the conformational changes observed by CD. Importantly, there is a
correlation between the number of Alkyl-groups (CH3 -) on the amine of the
osmolyte and enhanced helicity of the 15-repeat silk-mimetic for the osmolytes
tested, ie TMANO, Betaine, Sarcosine and Glycine. These preliminary results are
applicable to storing and processing recombinant silk sequences in H2 O, an
important mile-stone for widespread use of recombinant silk polymers.
PMID- 27488928
TI - Residual risk and waste in donated blood with pooled nucleic acid testing.
AB - An accurate estimation of the residual risk of transfusion-transmittable
infections (TTIs), which includes the human immunodeficiency virus (HIV),
hepatitis B and C viruses (HBV, HCV), among others, is essential, as it provides
the basis for blood screening assay selection. While the highly sensitive nucleic
acid testing (NAT) technology has recently become available, it is highly costly.
As a result, in most countries, including the United States, the current practice
for human immunodeficiency virus, hepatitis B virus, hepatitis C virus screening
in donated blood is to use pooled NAT. Pooling substantially reduces the number
of tests required, especially for TTIs with low prevalence rates. However,
pooling also reduces the test's sensitivity, because the viral load of an
infected sample might be diluted by the other samples in the pool to the point
that it is not detectable by NAT, leading to potential TTIs. Infection-free blood
may also be falsely discarded, resulting in wasted blood. We derive expressions
for the residual risk, expected number of tests, and expected amount of blood
wasted for various two-stage pooled testing schemes, including Dorfman-type and
array-based testing, considering infection progression, infectivity of the blood
unit, and imperfect tests under the dilution effect and measurement errors. We
then calibrate our model using published data and perform a case study. Our study
offers key insights on how pooled NAT, used within different testing schemes,
contributes to the safety and cost of blood. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27488927
TI - Inhibition of the 3-hydroxy-3-methyl-glutaryl-CoA reductase induces orofacial
defects in zebrafish.
AB - BACKGROUND: Orofacial clefts (OFCs) are common birth defects, which include a
range of disorders with a complex etiology affecting formation of craniofacial
structures. Some forms of syndromic OFCs are produced by defects in the
cholesterol pathway. The principal enzyme of the cholesterol pathway is the 3
hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Our aim is to study whether
defects of HMGCR function would produce orofacial malformation similar to those
found in disorders of cholesterol synthesis. METHODS: We used zebrafish hmgcrb
mutants and HMGCR inhibition assay using atorvastatin during early and late
stages of orofacial morphogenesis in zebrafish. To describe craniofacial
phenotypes, we stained cartilage and bone and performed in situ hybridization
using known craniofacial markers. Also, we visualized neural crest cell migration
in a transgenic fish. RESULTS: Our results showed that mutants displayed loss of
cartilage and diminished orofacial outgrowth, and in some cases palatal cleft.
Late treatments with statin show a similar phenotype. Affected-siblings displayed
a moderate phenotype, whereas early-treated embryos had a minor cleft. We found
reduced expression of the downstream component of Sonic Hedgehog-signaling gli1
in ventral brain, oral ectoderm, and pharyngeal endoderm in mutants and in late
atorvastatin-treated embryos. CONCLUSION: Our results suggest that HMGCR loss-of
function primarily affects postmigratory cranial neural crest cells through
abnormal Sonic Hedgehog signaling, probably induced by reduction in metabolites
of the cholesterol pathway. Malformation severity correlates with the grade of
HMGCR inhibition, developmental stage of its disruption, and probably with
availability of maternal lipids. Together, our results might help to understand
the spectrum of orofacial phenotypes found in cholesterol synthesis disorders.
Birth Defects Research (Part A) 106:814-830, 2016. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27488929
TI - Intratubular large cell hyalinizing Sertoli cell tumor of the testis presenting
with prepubertal gynecomastia: a case report.
AB - Intratubular large cell hyalinizing Sertoli cell neoplasia (ITLCHSCN) resulting
from Sertoli cells of the testis are mainly reported in young adults and these
are rarely seen in childhood. The most common presenting symptoms of the patients
diagnosed with ITLCHSCN are gynecomastia, enlargement in the testicles, increase
in growth velocity, and advanced bone age. Symptoms are basically resulting from
increased aromatase enzyme activity in Sertoli cells. In this case report, an
eight-and-a-half-year-old case presenting with complaint of bilateral
gynecomastia since two years, showing no endocrine abnormality in laboratory
during two years of follow-up, determined to have progression in bilateral
gynecomastia, increase in testicular volumes, advanced bone age, increase in
growth velocity in the clinical follow-up, and diagnosed with ITLCHSCN after
testis biopsy was presented.
PMID- 27488930
TI - Persistence of rubella and mumps antibodies, following changes in the recommended
age for the second dose of MMR vaccine in Portugal.
AB - In Portugal, the recommended age for the second dose of MMR (MMR2) was changed
from 10-13 years to 5-6 years for those born in 1994 and afterwards. This study
aimed to assess if MMR schedule and time elapsed from the last dose are
associated with the concentration of rubella and mumps IgG antibodies. Three
Portuguese birth cohorts (convenience samples) were selected for this study (66,
59 and 41 participants born respectively in 1990-1993, 1994-1995 and 2001-2003).
Geometric mean concentrations (GMC) for mumps IgG were respectively 36, 30 and 38
RU/ml (P = 0.236) and for rubella IgG were 18, 20 and 17 IU/ml (P = 0.641). For
both specific antibodies, no differences were observed with time since MMR2.
Receiving MMR2 at 5-6 or 10-13 years was not associated with concentration of
both antibodies. The GMC of rubella IgG was lower in males (P = 0.029). Taking
into account previous evidence and the logistics needed to change vaccination
schedules, it seems reasonable that sustaining very high coverage with two doses
of MMR is currently the most pragmatic way to control mumps and rubella rather
than any changes to the schedule.
PMID- 27488931
TI - The influence of prostate-specific antigen density on positive and negative
predictive values of multiparametric magnetic resonance imaging to detect Gleason
score 7-10 prostate cancer in a repeat biopsy setting.
AB - OBJECTIVES: To evaluate the influence of prostate-specific antigen density (PSAD)
on positive (PPV) and negative (NPV) predictive values of multiparametric
magnetic resonance imaging (mpMRI) to detect Gleason score >=7 cancer in a repeat
biopsy setting. PATIENTS AND METHODS: Retrospective study of 514 men with
previous prostate biopsy showing no or Gleason score 6 cancer. All had mpMRI,
graded 1-5 on a Likert scale for cancer suspicion, and subsequent targeted and 24
core systematic image-fusion guided transperineal biopsy in 2013-2015. The NPVs
and PPVs of mpMRIs for detecting Gleason score >=7 cancer were calculated (+/-95%
confidence intervals) for PSAD <=0.1, 0.1-0.2, <=0.2 and >0.2 ng/mL/mL, and
compared by chi-square test for linear trend. RESULTS: Gleason score >=7 cancer
was detected in 31% of the men. The NPV of Likert 1-2 mpMRI was 0.91 (+/-0.04)
with a PSAD of <=0.2 ng/mL/mL and 0.71 (+/-0.16) with a PSAD of >0.2 ng/mL/mL (P
= 0.003). For Likert 3 mpMRI, PPV was 0.09 (+/-0.06) with a PSAD of <=0.2
ng/mL/mL and 0.44 (+/-0.19) with a PSAD of >0.2 ng/mL/mL (P = 0.002). PSAD also
significantly affected the PPV of Likert 4-5 mpMRI lesions: the PPV was 0.47 (+/
0.08) with a PSAD of <=0.2 ng/mL/mL and 0.66 (+/-0.10) with a PSAD of >0.2
ng/mL/mL (P < 0.001). CONCLUSION: In a repeat biopsy setting, a PSAD of <=0.2
ng/mL/mL is associated with low detection of Gleason score >=7 prostate cancer,
not only in men with negative mpMRI, but also in men with equivocal imaging.
Surveillance, rather than repeat biopsy, may be appropriate for these men.
Conversely, biopsies are indicated in men with a high PSAD, even if an mpMRI
shows no suspicious lesion, and in men with an mpMRI suspicious for cancer, even
if the PSAD is low.
PMID- 27488932
TI - Pathological Features of Fatal Crocodile Attacks in Northern Australia, 2005
2014.
AB - Eleven deaths from crocodile attacks in the Northern Territory, Australia were
reviewed. The male:female ratio was 8:3; age range-10-62 years, average 29.4
years. Four children were included (one boy and three girls, aged 10, 11, and two
at 12 years), and there were seven aboriginal victims (64%). The attacks were
witnessed in eight cases with the victims swimming in freshwater N = 5, standing
on a river bank N = 1, fishing in fresh water N = 1, or diving in the sea N = 1.
At autopsy, several distinct patterns of injury were observed ranging from
complete traumatic disruption of the body with only incomplete remains for
examination (N = 5), to crushing of the head with fractures of the skull (N = 4),
crushing of the chest with fractures of the ribs and sternum (N = 2), and
avulsion of limbs (N = 4). In one case, there was decapitation. Autopsy
evaluations were complicated by decomposition and loss of body parts.
PMID- 27488933
TI - Effect of the allelic variants of ABCB1, CYP2D6 and HTR3B on response of
ramosetron to prevent chemotherapy-induced nausea and vomiting in Korean cancer
patients.
AB - AIM: Despite appropriate use of antiemetics including 5-hydroxytryptamine type 3
(5-HT3 ) receptor antagonists, chemotherapy-induced nausea and vomiting (CINV) is
still an unsolved problem in patients with anticancer drugs. We examined whether
the variants of ABCB1, CYP2D6 and HTR3B affect efficacy of ramosetron, a
selective 5-HT3 receptor antagonist in a dose escalation clinical trial. METHODS:
We conducted a clinical trial on patients who underwent FOLFOX combination
chemotherapy. The participants were randomized into three groups of ramosetron:
0.3 mg (standard dose), 0.45 mg and 0.6 mg. Rhodes index of nausea, vomiting and
retching were measured at 1, 6 h, day 1, day 2 and day 7 after the administration
of ramosetron as a clinical parameter of CINV and polymorphism was analyzed from
genomic DNA. RESULTS: There was a dose-dependent decrease in the nausea and
vomiting scores at day 1 and day 2, not statistically significant. The Rhodes
index of nausea, vomiting and retching score at day 1 in participants with HTR3B
100_-102delAAG deletion variants was significantly higher than wild type
participants, regardless of dosages. However, the polymorphisms including ABCB1,
CYP2D6 and other HTR3B genes did not affect response to ramosetron after
chemotherapy. CONCLUSION: These results suggest that the -AAG deletion variant of
the 5-HT3B receptor gene may contribute to variability in response to antiemetic
therapy for CINV regardless of dose escalation. These results suggest that
carrying a -100_-102delAAG variant of 5-HT3 gene should be supported by alternate
or additive antiemetics in addition to 5-HT3 antagonists to control acute emesis.
PMID- 27488934
TI - The CelluTome epidermal graft-harvesting system: a patient-reported outcome
measure and cost evaluation study.
AB - Conventional split skin grafts (SSG) require anaesthesia, specialist equipment
and can have high donor site (DS) morbidity. The CelluTome epidermal graft
harvesting device is a novel alternative, providing pain-free epidermal skin
grafts (ESG) in the outpatient setting, with projected minimal DS trauma and
improved patient satisfaction. This study aimed to compare ESG with SSG by
evaluating patient-related outcome measures (PROMs) and the cost implications of
both. Twenty patients answered a graft satisfaction questionnaire that evaluated:
donor/graft site noticeability, aesthetic concerns, adverse problems and patient
satisfaction. Cost/patient was calculated based on total operative expenses and
five clinic follow-ups. In 100% of the ESG cases, there were no DS noticeability
or adverse problems compared to 25% in the SSG group. Complete satisfaction with
DS appearance was observed in 100% of the ESG cases (50% SSG). Noticeability,
adverse problems and overall satisfaction were significantly better in ESG cases
(P < 0.05). Graft site parameters were comparable with similar healing outcomes.
The cost per patient for ESG was L431 and L1489 for SSG, with an annual saving of
L126 960 based on 10 grafts/month. For the right patient, CelluTome provides
comparable wound healing, with reduced DS morbidity and higher patient
satisfaction.
PMID- 27488935
TI - Assumption-versus data-based approaches to summarizing species' ranges.
AB - For conservation decision making, species' geographic distributions are mapped
using various approaches. Some such efforts have downscaled versions of coarse
resolution extent-of-occurrence maps to fine resolutions for conservation
planning. We examined the quality of the extent-of-occurrence maps as range
summaries and the utility of refining those maps into fine-resolution
distributional hypotheses. Extent-of-occurrence maps tend to be overly simple,
omit many known and well-documented populations, and likely frequently include
many areas not holding populations. Refinement steps involve typological
assumptions about habitat preferences and elevational ranges of species, which
can introduce substantial error in estimates of species' true areas of
distribution. However, no model-evaluation steps are taken to assess the
predictive ability of these models, so model inaccuracies are not noticed.
Whereas range summaries derived by these methods may be useful in coarse-grained,
global-extent studies, their continued use in on-the-ground conservation
applications at fine spatial resolutions is not advisable in light of reliance on
assumptions, lack of real spatial resolution, and lack of testing. In contrast,
data-driven techniques that integrate primary data on biodiversity occurrence
with remotely sensed data that summarize environmental dimensions (i.e.,
ecological niche modeling or species distribution modeling) offer data-driven
solutions based on a minimum of assumptions that can be evaluated and validated
quantitatively to offer a well-founded, widely accepted method for summarizing
species' distributional patterns for conservation applications.
PMID- 27488937
TI - An in situ FTIR spectroscopic and thermogravimetric analysis study of the
dehydration and dihydroxylation of SnO2: the contribution of the (100), (110) and
(111) facets.
AB - Nanoparticulate SnO2 produced by a hydrothermal method was characterised by BET,
XRD, TGA-MS and in situ variable temperature diffuse reflectance infra red
spectroscopy (DRIFTS) to determine the surface behaviour of water. For the (100)
facets, hydrogen bonding does not occur, and water adsorption is less strong than
for the (111) and (110) facets where hydrogen bonding does occur. Reversible
uptake of oxygen was observed. These findings have implications for other surface
gas reactions in which Ni and Sb co-doped SnO2 (NATO) anodes are used for ozone
generation. BET showed the relatively high surface area and nanometer scale of
the SnO2 particles, whilst XRD confirmed the nano dimension of the crystallites
and showed only the cassiterite phase. TGA analysis indicated four temperature
regions over which mass loss was observed. These and the in situ DRIFTS studies
revealed the existence of various forms of water associated with specific crystal
facets of the SnO2, as well as the existence of isolated O-H groups and adsorbed
oxygen species. Electronic absorptions were also observed and the data
rationalised in terms of the existence of both free electron absorptions, and
absorptions from oxygen vacancy states. The role of adsorbed molecular oxygen in
electrochemical ozone generation at Ni and Sb co-doped SnO2 (NATO) anodes was
strongly suggested by this work.
PMID- 27488938
TI - Synthetic receptor molecules for selective fluorescence detection of 8-oxo-dGTP
in aqueous media.
AB - A series of 9-hydroxy-1,3-diazaphenoxazine-2-one derivatives were synthesized as
fluorescent receptor molecules for 8-oxo-dGTP, which attach the cyclen-zinc
complex at the 3-N position as the binding site for the triphosphate and the (2
aryloxycarbonylamino)ethyl group at the 9-O position as the hydrogen bonding site
for 8-oxoguanine. Among these molecules, the receptor molecule 5a-Zn constructed
of the ethyl linker at 3-N and the (2-benzyloxycarbonyl amino)ethyl group at 9-O
displayed the best recognition ability for 8-oxoguanosine triphosphate (8-oxo
dGTP) in aqueous media. The receptor 5a-Zn was also shown to selectively detect 8
oxo-dGTP in a cell lysate solution.
PMID- 27488936
TI - Large-scale analysis reveals populational contributions of cortical spike rate
and synchrony to behavioural functions.
AB - KEY POINTS: There have been few systematic population-wide analyses of
relationships between spike synchrony within a period of several milliseconds and
behavioural functions. In this study, we obtained a large amount of spike data
from > 23,000 neuron pairs by multiple single-unit recording from deep layer
neurons in motor cortical areas in rats performing a forelimb movement task. The
temporal changes of spike synchrony in the whole neuron pairs were statistically
independent of behavioural changes during the task performance, although some
neuron pairs exhibited correlated changes in spike synchrony. Mutual information
analyses revealed that spike synchrony made a smaller contribution than spike
rate to behavioural functions. The strength of spike synchrony between two
neurons was statistically independent of the spike rate-based preferences of the
pair for behavioural functions. ABSTRACT: Spike synchrony within a period of
several milliseconds in presynaptic neurons enables effective integration of
functional information in the postsynaptic neuron. However, few studies have
systematically analysed the population-wide relationships between spike synchrony
and behavioural functions. Here we obtained a sufficiently large amount of spike
data among regular-spiking (putatively excitatory) and fast-spiking (putatively
inhibitory) neuron subtypes (> 23,000 pairs) by multiple single-unit recording
from deep layers in motor cortical areas (caudal forelimb area, rostral forelimb
area) in rats performing a forelimb movement task. After holding a lever, rats
pulled the lever either in response to a cue tone (external-trigger trials) or
spontaneously without any cue (internal-trigger trials). Many neurons exhibited
functional spike activity in association with forelimb movements, and the
preference of regular-spiking neurons in the rostral forelimb area was more
biased toward externally triggered movement than that in the caudal forelimb
area. We found that a population of neuron pairs with spike synchrony does exist,
and that some neuron pairs exhibit a dependence on movement phase during task
performance. However, the population-wide analysis revealed that spike synchrony
was statistically independent of the movement phase and the spike rate-based
preferences of the pair for behavioural functions, whereas spike rates were
clearly dependent on the movement phase. In fact, mutual information analyses
revealed that the contribution of spike synchrony to the behavioural functions
was small relative to the contribution of spike rate. Our large-scale analysis
revealed that cortical spike rate, rather than spike synchrony, contributes to
population coding for movement.
PMID- 27488939
TI - Evolutionary dynamics of selfish DNA explains the abundance distribution of
genomic subsequences.
AB - Since the sequencing of large genomes, many statistical features of their
sequences have been found. One intriguing feature is that certain subsequences
are much more abundant than others. In fact, abundances of subsequences of a
given length are distributed with a scale-free power-law tail, resembling
properties of human texts, such as Zipf's law. Despite recent efforts, the
understanding of this phenomenon is still lacking. Here we find that selfish DNA
elements, such as those belonging to the Alu family of repeats, dominate the
power-law tail. Interestingly, for the Alu elements the power-law exponent
increases with the length of the considered subsequences. Motivated by these
observations, we develop a model of selfish DNA expansion. The predictions of
this model qualitatively and quantitatively agree with the empirical
observations. This allows us to estimate parameters for the process of selfish
DNA spreading in a genome during its evolution. The obtained results shed light
on how evolution of selfish DNA elements shapes non-trivial statistical
properties of genomes.
PMID- 27488940
TI - Containment of Ebola and Polio in Low-Resource Settings Using Principles and
Practices of Emergency Operations Centers in Public Health.
AB - Emergency Operations Centers (EOCs) have been credited with driving the recent
successes achieved in the Nigeria polio eradication program. EOC concept was also
applied to the Ebola virus disease outbreak and is applicable to a range of other
public health emergencies. This article outlines the structure and functionality
of a typical EOC in addressing public health emergencies in low-resource
settings. It ascribes the successful polio and Ebola responses in Nigeria to
several factors including political commitment, population willingness to engage,
accountability, and operational and strategic changes made by the effective use
of an EOC and Incident Management System. In countries such as Nigeria where the
central or federal government does not directly hold states accountable, the EOC
provides a means to improve performance and use data to hold health workers
accountable by using innovative technologies such as geographic position systems,
dashboards, and scorecards.
PMID- 27488941
TI - Impact of preoperative antithrombotic therapy on blood management after
implantation of primary total knee arthroplasty.
AB - Red blood cell concentrates (RCC) substitution after total knee arthroplasty
(TKA) is correlated with multifold of complications and an independent predictor
for higher postoperative mortality. TKA is mainly performed in elderly patients
with pre-existing polymorbidity, often requiring permanent preoperative
antithrombotic therapy (PAT). The aim of this retrospective analysis was to
investigate the impact of demand for PAT on inpatient blood management in
patients undergoing TKA. In this study 200 patients were retrospectively
evaluated after TKA for differences between PAT and non-PAT regarding demographic
parameters, preoperative ASA score > 2, duration of operation, pre-, and
intraoperative hemoglobin level, and postoperative parameters including amount of
wound drainage, RCC requirement, and inpatient time. In a multivariate logistic
regression analysis the independent influences of PAT, demographic parameters,
ASA score > 2, and duration of the operation on RCC demand following TKA were
analyzed. Patients with PAT were significantly older, more often had an ASA > 2
at surgery, needed a higher number of RCCs units and more frequently and had
lower perioperative hemoglobin levels. Multivariate logistic regression revealed
PAT was an independent predictor for RCC requirement. PAT patients are more
likely to require RCC following TKA and should be accurately monitored with
respect to postoperative blood loss.
PMID- 27488942
TI - Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel
Lecture).
AB - Malaria has long been a devastating and life-threatening global epidemic disease
in human history. Artemisinin, the active substance against malaria, was first
isolated and tested in the 1970s in China. The important role played by
traditional Chinese medicine in the discovery of artemisinin is described by Y.
Tu in her Nobel Lecture.
PMID- 27488943
TI - New hope for chronic myelogenous leukemia patients: dasatinib offers better
efficacy with shorter treatment.
AB - Although the discovery of tyrosine kinase inhibitors (TKIs) has dramatically
improved the prognoses of chronic myelogenous leukemia (CML) patients, a cure has
remained elusive. Unanswered questions include how long must a patient continue
on TKI therapy, and how does a patient know when he/she can safely stop or finish
this therapy? Imagawa et al. have carefully addressed these questions of safety
and efficacy using a stop study of the second-generation TKI dasatinib. The
results of a multicenter phase II trial termed the "dasatinib discontinuation"
(DADI) trial indicated that 48% (30/63) of CML patients who had maintained a deep
molecular response (DMR) to second-line or subsequent dasatinib therapy for at
least for 1 year did not show any signs of disease relapse. Thus, even after it
is stopped, dasatinib treatment may decrease the chance of disease relapse and
provide a curative benefit to CML patients. This work by Imagawa et al. strongly
supports the clinical utility of the second-generation TKI dasatinib for CML
treatment.
PMID- 27488944
TI - An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the
growth rate of small abdominal aortic aneurysms: a randomised placebo-controlled
trial (AARDVARK).
AB - BACKGROUND: Although data are inconsistent, angiotensin-converting enzyme
inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal
aortic aneurysm (AAA) rupture in analysis of administrative databases.
OBJECTIVES: (1) To investigate whether or not the ACE-I perindopril (Coversyl
arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood
pressure (BP)-independent effects of perindopril on small AAA growth and to
compare the repeatability of measurement of internal and external aneurysm
diameters. DESIGN: A three-arm, multicentre, single-blind, randomised placebo
controlled trial. SETTING: Fourteen hospitals in England. PARTICIPANTS: Men or
women aged >= 55 years with an AAA of 3.0-5.4 cm in diameter by internal or
external measurement according to ultrasonography and who met the trial
eligibility criteria. INTERVENTIONS: Patients were randomised to receive 10 mg of
perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily
or placebo daily. MAIN OUTCOME MEASURES: The primary outcome was AAA diameter
growth using external measurements in the longitudinal plane, which in-trial
studies suggested was the preferred measure. Secondary outcome measures included
AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the
threshold for intervention (5.5 cm) or referral for surgery, tolerance of study
medication (measured by compliance, adverse events and quality of life) and a
comparison of the repeatability of measures of internal and external AAA
diameter. Patients were followed up every 3-6 months over 2 years. RESULTS: In
total, 227 patients were recruited and randomised into the three groups, which
were generally well matched at baseline. Multilevel modelling was used to
determine the maximum likelihood estimates for AAA diameter growth. No
significant differences in the estimates of annual growth were apparent [1.68
(standard error 0.02) mm, 1.77 (0.02) mm and 1.81 (0.02) mm in the placebo,
perindopril and amlodipine groups, respectively]. Similarly, no significant
differences in the slopes of modelled growth over time were apparent between
perindopril and placebo (p = 0.78) or between perindopril and amlodipine (p =
0.89). The results were essentially unaffected by adjustment for potential
confounders. Compliance, measured by pill counts, was good throughout (> 80% at
all visit time points). There were no significant in-trial safety concerns. Six
patients withdrew because of adverse events attributed to the study medications
(n = 2 perindopril, n = 4 amlodipine). No patients ruptured their AAA and 27
underwent elective surgery during the trial (n = 9 placebo, n = 10 perindopril, n
= 8 amlodipine). CONCLUSIONS: We were unable to demonstrate a significant impact
of perindopril compared with placebo or amlodipine on small AAA growth over a 2
year period. Furthermore, there were no differences in the times to reach a
diameter of 5.5 cm or undergo surgery among the three groups. Perindopril and
amlodipine were well tolerated by this population. External AAA measurements were
found to be more repeatable than internal measurements. The observed AAA growth
measurement variability was greater than that expected pre trial. This, combined
with slower than expected mean growth rates, resulted in our having limited power
to detect small differences between growth rates and hence this adds uncertainty
to the interpretation of the results. Several further analyses are planned
including a multivariate analysis of determinants of AAA growth, an evaluation of
the possible differential effect of perindopril on fast AAA growth and an
investigation into the roles of central BP and BP variability on AAA growth.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN51383267. 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. 20, No. 59. See the NIHR Journals Library website for
further project information. The NIHR Biomedical Research Centre based at
Imperial College NHS Trust supported the trial. Servier provided perindopril at
no charge.
PMID- 27488946
TI - Phylogeographic Patterns in Africa and High Resolution Delineation of Genetic
Clades in the Lion (Panthera leo).
AB - Comparative phylogeography of African savannah mammals shows a congruent pattern
in which populations in West/Central Africa are distinct from populations in
East/Southern Africa. However, for the lion, all African populations are
currently classified as a single subspecies (Panthera leo leo), while the only
remaining population in Asia is considered to be distinct (Panthera leo persica).
This distinction is disputed both by morphological and genetic data. In this
study we introduce the lion as a model for African phylogeography. Analyses of
mtDNA sequences reveal six supported clades and a strongly supported ancestral
dichotomy with northern populations (West Africa, Central Africa, North
Africa/Asia) on one branch, and southern populations (North East Africa,
East/Southern Africa and South West Africa) on the other. We review taxonomies
and phylogenies of other large savannah mammals, illustrating that similar clades
are found in other species. The described phylogeographic pattern is considered
in relation to large scale environmental changes in Africa over the past 300,000
years, attributable to climate. Refugial areas, predicted by climate envelope
models, further confirm the observed pattern. We support the revision of current
lion taxonomy, as recognition of a northern and a southern subspecies is more
parsimonious with the evolutionary history of the lion.
PMID- 27488947
TI - Metformin Enhances the Therapy Effects of Anti-IGF-1R mAb Figitumumab to NSCLC.
AB - The insulin-like growth factor (IGF) signaling system plays a critical role in
tumorigenesis, highlighting the potential of targeting IGF-1R as an anti-cancer
therapy. Although multiple anti-IGF-1R monoclonal antibody (mAb) drugs have been
developed, challenges remain in the validation of the therapeutic effects and
understanding the molecular mechanism of these mAbs. Herein, we conducted a study
to validate the effect of Figitumumab (CP), an anti-IGF-1R mAb, in a panel of non
small cell lung cancer (NSCLC) cell lines. We found all tested cell lines were
sensitive to CP, and CP could block IGF-1R and the downstream PI3K/AKT pathway
activation. Unexpectedly, we found CP could activate ERK signaling pathway in IGF
1R kinase independent manner, which we further verified was mainly mediated by
beta-arrestin2. We also investigated the anti-tumor effect of metformin alone as
well as its combination with CP to target NSCLC. Metformin could target IGF-1R
signaling pathway by attenuating PI3K/AKT and MEK/ERK signaling pathways and down
regulating IGF-1R. Finally, we found that combining metformin with CP could
further induce IGF-1R down-regulation and was more effective to target NSCLC
cells. Our data suggests the combining of metformin with CP has additive
therapeutic value against NSCLC.
PMID- 27488948
TI - Novel reovirus associated with epidemic mortality in wild largemouth bass
(Micropterus salmoides).
AB - Reoviruses (family Reoviridae) infect vertebrate and invertebrate hosts with
clinical effects ranging from inapparent to lethal. Here, we describe the
discovery and characterization of Largemouth bass reovirus (LMBRV), found during
investigation of a mortality event in wild largemouth bass (Micropterus
salmoides) in 2015 in WI, USA. LMBRV has spherical virions of approximately 80 nm
diameter containing 10 segments of linear dsRNA, aligning it with members of the
genus Orthoreovirus, which infect mammals and birds, rather than members of the
genus Aquareovirus, which contain 11 segments and infect teleost fishes. LMBRV is
only between 24 % and 68 % similar at the amino acid level to its closest
relative, Piscine reovirus (PRV), the putative cause of heart and skeletal muscle
inflammation of farmed salmon. LMBRV expands the known diversity and host range
of its lineage, which suggests that an undiscovered diversity of related
pathogenic reoviruses may exist in wild fishes.
PMID- 27488949
TI - More tolerance for dendritic cells in psoriasis.
PMID- 27488950
TI - Photoactive platinum(ii) beta-diketonates as dual action anticancer agents.
AB - Platinum(ii) complexes, viz. [Pt(L)(cur)] (1), [Pt(L)(py-acac)] (2) and [Pt(L)(an
acac)] (3), where HL is 4,4'-bis-dimethoxyazobenzene, Hcur is curcumin, Hpy-acac
and Han-acac are pyrenyl and anthracenyl appended acetylacetone, were prepared,
characterized and their anticancer activities were studied. Complex [Pt(L)(acac)]
(4) was used as a control. Complex 1 showed an absorption band at 430 nm (epsilon
= 8.8 * 10(4) M(-1) cm(-1)). The anthracenyl and pyrenyl complexes displayed
bands near 390 nm (epsilon = 3.7 * 10(4) for 3 and 4.4 * 10(4) M(-1) cm(-1) for
2). Complex 1 showed an emission band at 525 nm (Phi = 0.017) in 10% DMSO-DPBS
(pH, 7.2), while 2 and 3 were blue emissive (lambdaem = 440 and 435, Phi = 0.058
and 0.045). There was an enhancement in emission intensity on glutathione (GSH)
addition indicating diketonate release. The platinum(ii) species thus formed
acted as a transcription inhibitor. The released beta-diketonate base showed
photo-chemotherapeutic activity. The complexes photocleaved plasmid DNA under
blue light of 457 nm forming ~75% nicked circular (NC) DNA with hydroxyl radicals
and singlet oxygen as the ROS. Complexes 1-3 were photocytotoxic in skin
keratinocyte HaCaT cells giving IC50 of 8-14 MUM under visible light (400-700 nm,
10 J cm(-2)), while being non-toxic in the dark (IC50: ~60 MUM). Complex 4 was
inactive. Complexes 1-3 generating cellular ROS caused apoptotic cell death under
visible light as evidenced from DCFDA and annexin-V/FITC-PI assays. This work
presents a novel way to deliver an active platinum(ii) species and a phototoxic
beta-diketone species to the cancer cells.
PMID- 27488951
TI - Intraperitoneal injection (IP), Intravenous injection (IV) or anal injection
(AI)? Best way for mesenchymal stem cells transplantation for colitis.
AB - Stem cell transplantation showed promising results in IBD management. However,
the therapeutic impacts of cell delivery route that is critical for clinical
translation are currently poorly understood. Here, three different MSCs delivery
routes: intraperitoneal (IP), intravenous (IV), and anal injection (AI) were
compared on DSS-induced colitic mice model. The overall therapeutic factors, MSCs
migration and targeting as well as local immunomodulatory cytokines and FoxP3(+)
cells infiltration were analyzed. Colitis showed varying degrees of alleviation
after three ways of MSCs transplantation, and the IP injection showed the highest
survival rate of 87.5% and displayed the less weight loss and quick weight gain.
The fecal occult blood test on the day 3 also showed nearly complete absence of
occult blood in IP group. The fluorescence imaging disclosed higher intensity of
engrafted cells in inflamed colon and the corresponding mesentery lymph nodes
(MLNs) in IP and AI groups than the IV group. Real time-PCR and ELISA also
demonstrate lower TNF-alpha and higher IL-10, TSG-6 levels in IP group. The
immunohistochemistry indicated higher repair proliferation (Ki-67) and more
FoxP3(+) cells accumulation of IP group. IP showed better colitis recovery and
might be the optimum MSCs delivery route for the treatment of DSS-induced
colitis.
PMID- 27488952
TI - Postoperative ileus: in search of an international consensus on definition,
diagnosis, and treatment.
AB - PURPOSE: Postoperative ileus (POI) is a frequent complication after abdominal
surgery; nonetheless, it remains poorly defined. Our aim was to achieve an
international consensus among leading colorectal surgeons on definition,
prevention, and treatment of POI. METHODS: Thirty-five experts from five
continents participated in a three-round Delphi process. Round 1 contained open
ended questions on POI and postoperative nausea and vomiting (PONV). Round 2
included closed-ended questions. Round 3 measured agreement on a 5-point Likert
scale. Consensus was defined when items were rated as agree or strongly agree by
at least 70 % of the experts. RESULTS: Experts reached following consensus: POI
is a temporary inhibition (86 %) of gastrointestinal motility after surgical
intervention due to non-mechanical causes (89 %) and prevents sufficient oral
intake (96 %). Abdominal distension/tenderness are the most relevant clinical
signs (71 %). Nasogastric tube placement is not mandatory (78 %) but can be
removed without previous clamping (81 %)/gastrointestinal contrast study (100 %).
Preventive measures are recommended to decrease the risk of POI (96 %): narcotic
sparing analgesia (89 %) and fluid optimization (74 %). Treatment of POI should
include stimulation of ambulation (96 %) and stop of opioids (74 %). Total
parenteral nutrition is recommended from the 7th day without sufficient oral
intake (81 %). There was no consensus on the ranking of POI's symptoms, on the
imaging modality of choice for the diagnosis of POI, neither on the difference
between POI and PONV. CONCLUSIONS: This Delphi study achieved consensus on the
definition, relevant clinical signs, prevention, treatment, and supportive care
of POI. Areas of non-consensus were identified (necessity and modality of
radiologic imaging to establish the diagnosis, difference between POI and PONV),
giving opportunity for further research.
PMID- 27488953
TI - Gastric cancer from operating theatre to bench in Korea.
PMID- 27488954
TI - Ionic imbalance induced self-propulsion of liquid metals.
AB - Components with self-propelling abilities are important building blocks of small
autonomous systems and the characteristics of liquid metals are capable of
fulfilling self-propulsion criteria. To date, there has been no exploration
regarding the effect of electrolyte ionic content surrounding a liquid metal for
symmetry breaking that generates motion. Here we show the controlled actuation of
liquid metal droplets using only the ionic properties of the aqueous electrolyte.
We demonstrate that pH or ionic concentration gradients across a liquid metal
droplet induce both deformation and surface Marangoni flow. We show that the
Lippmann dominated deformation results in maximum velocity for the self
propulsion of liquid metal droplets and illustrate several key applications,
which take advantage of such electrolyte-induced motion. With this finding, it is
possible to conceive the propulsion of small entities that are constructed and
controlled entirely with fluids, progressing towards more advanced soft systems.
PMID- 27488956
TI - Biosequestration of copper by bacteria isolated from an abandoned mine by using
microbially induced calcite precipitation.
AB - Abandoned mine sites are frequently polluted with high concentrations of heavy
metals. In this study, 25 calcite-forming bacteria were newly isolated from the
soil of an abandoned metal mine in Korea. Based on their urease activity, calcite
production, and resistance to copper toxicity, four isolates were selected and
further identified by 16S rRNA gene sequencing. Among the isolates, Sporosarcina
soli B-22 was selected for subsequent copper biosequestration studies, using the
sand impermeability test by production of calcite and extracellular polymeric
substance. High removal rates (61.8%) of copper were obtained when the sand
samples were analyzed using an inductively coupled plasma-optical emission
spectrometer following 72 h of incubation. Scanning electron microscopy showed
that the copper carbonate precipitates had a diameter of approximately 5-10 MUm.
X-ray diffraction further confirmed the presence of copper carbonate and calcium
carbonate crystals.
PMID- 27488955
TI - Propofol Is Mitochondrion-Toxic and May Unmask a Mitochondrial Disorder.
AB - There are indications that preexisting mitochondrial disorders or beta-oxidation
defects predispose for propofol infusion syndrome. This review aimed at
investigating if propofol infusion syndrome occurs exclusively in patients with
mitochondrial disorder and if propofol can unmask a mitochondrial disorder.
Propofol infusion syndrome has been reported in genetically confirmed
mitochondrial disorder patients. In addition, muscle biopsy of patients with
propofol infusion syndrome revealed complex IV or complex II deficiency. In
animal studies propofol disrupted the electron flow along the respiratory chain
and decreased complex I, complex II, and complex III of the respiratory chain. In
addition, propofol disrupted the permeability transition pore and reduced the
mitochondrial membrane potential. In conclusion, propofol is mitochondrion-toxic
and mitochondrial disorder patients should not receive propofol in high dosages
over a prolonged period of time. Short-term application of propofol should be
safe even in mitochondrial disorder patients. Not only does propofol infusion
syndrome occur in mitochondrial disorder patients, but mitochondrial disorder
patients are likely at higher risk to develop propofol infusion syndrome.
Patients who develop propofol infusion syndrome should be screened for
mitochondrial disorder. Propofol infusion syndrome is preventable if risk factors
are thoroughly assessed, and if long-term propofol is avoided in patients at risk
for propofol infusion syndrome.
PMID- 27488957
TI - Rhodococcus jostii RHA1 TadA-homolog deletion mutants accumulate less
polyhydroxyalkanoates (PHAs) than the parental strain.
PMID- 27488958
TI - Corticosteroids: the knee jerk response.
PMID- 27488959
TI - When Terminal Illness Is Worse Than Death: A Multicenter Study of Health-Care
Providers' Resuscitation Desires.
AB - PURPOSE: To investigate how a terminal illness may affect the health-care
providers' resuscitation preferences. METHODS: We conducted a cross-sectional
survey in 9 health-care institutions located in 4 geographical regions in North
and Central America, investigating attitudes toward end-of-life practices in
health-care providers. Statistical analysis included descriptive statistics and
chi2 test for the presence of associations ( P < 0.05 being significant) and
Cramer V for the strength of the association. The main outcome measured the
correlation between the respondents' present code status and their preference for
cardiopulmonary resuscitation (CPR) in case of terminal illness. RESULTS: A total
of 852 surveys were completed. Among the respondents, 21% (n = 180) were
physicians, 36.9% (n = 317) were nurses, 10.5% (n = 90) were medical students,
and 265 participants were other staff members of the institutions. Most
respondents (58.3%; n = 500) desired "definitely full code" (physicians 73.2%; n
= 131), only 13.8% of the respondents (physicians 8.33%; n = 15) desired
"definitely no code" or "partial support," and 20.9% of the respondents (n = 179;
among physicians 18.4%; n = 33) had never considered their code status. There was
an association between current code status and resuscitation preference in case
of terminal illness ( P < .001), but this association was overall quite weak
(Cramer V = 0.180). Subgroup analysis revealed no association between current
code status and terminal illness code preference among physicians ( P = .290) and
nurses ( P = .316), whereupon other hospital workers were more consistent ( P <
.01, Cramer V = .291). CONCLUSION: Doctors and nurses have different end-of-life
preferences than other hospital workers. Their desire to undergo CPR may change
when facing a terminal illness.
PMID- 27488960
TI - Macondo oil in deep-sea sediments: Part 1 - sub-sea weathering of oil deposited
on the seafloor.
AB - Chemical analysis of sediment cores collected up to 8km from the Macondo well in
2010/2011 demonstrates the extent of weathering of the Macondo oil deposited in
deep-sea sediments following the Deepwater Horizon disaster. On average,
dissolution and biodegradation of the oil on the seafloor increased with distance
from the well indicating that weathering occurred rapidly and overwhelmingly
during the oil's transport as dispersed oil droplets within the deep-sea plume.
Beyond about 5km from the well, the oil deposited on the seafloor had lost most
mass below C25, was relatively enriched in n-C25+ n-alkanes and C3- and C4
alkylated benz[a]anthracenes/chrysenes, the latter owing to 95% depletion of
total PAHs. Biodegradation of C28 and C29 tricyclic terpanes, C34 and C35
17alpha(H),21beta(H)-homohopanes, C27 13beta(H),17alpha(H)-dia and C27
14beta(H),17beta(H)-steranes and dissolution of C26 to C28 triaromatic steroids
occurred. The results provide a means to distinguish Macondo oil in deep-sea
sediments from naturally-occurring seep oils and pervasive ambient background
hydrocarbons.
PMID- 27488961
TI - Curvature of iris profile in spectral domain optical coherence tomography and
dependency to refraction, age and pupil size - the MIPH Eye&Health Study.
AB - PURPOSE: Optical coherence tomography (OCT) of the anterior segment allows
quantitative analysis of the geometry of the iris. We performed spectral domain
OCT examinations in healthy emmetropic, hyperopic and myopic subjects to
investigate iris curvature and its associations. METHODS: In a cross-sectional
study, out of 4617 eyes (2309 subjects) those with refractive errors of <-4 or
>+3 dioptres were identified by objective refraction. The iris was examined using
the anterior segment mode of a spectral domain 3D OCT-2000 (Topcon Inc., Japan)
in the temporal meridian, and OCT scans were investigated with respect to
presence and amount of convex and concave iris configuration. Ninety-three eyes
of 50 subjects served as emmetropic group (-0.5 <= x <=+0.5 dioptres). Previous
ocular surgery was exclusion criterion. RESULTS: Six hundred and sixty-eight eyes
of 398 persons [292 male (76%); age range; 18-66 years] were included in the
study. In the myopic group, 105 eyes had a concave iris configuration (26%),
while in the hyperopic group, no eye had this configuration (0%) and in the
emmetropic group five eyes (5%). Convex iris configuration was found in 96% of
hyperopic, in 85% of the emmetropic and in 67% of the myopic eyes. There was an
association between concave iris configuration and myopia, younger age and male
gender, and with anterior chamber angle width. CONCLUSION: Spectral domain OCT
images can be used for analysis of the iris structure and geometry. Our results
are limited to the properties of the study population having an age range from 18
to 66 years and consisting mainly of men.
PMID- 27488963
TI - Primary Noncutaneous Malignant Melanoma of the Breast.
AB - Primary noncutaneous breast melanoma without an apparent skin primary lesion is
uncommon. Its pathogenesis is debated with some authors believing that it is a
metastatic disease from an undiscovered primary or a primary that has since
completely regressed but it may be a true primary tumor arising from ectopic
melanocytes. We present a case of a V600E BRAF mutation-positive primary
noncutaneous breast melanoma diagnosed at an early stage in a screening mammogram
as a solitary breast lesion without nodal involvement. Considerations of
treatment of this rare disease are discussed.
PMID- 27488962
TI - Normal stroma suppresses cancer cell proliferation via mechanosensitive
regulation of JMJD1a-mediated transcription.
AB - Tissue homeostasis is dependent on the controlled localization of specific cell
types and the correct composition of the extracellular stroma. While the role of
the cancer stroma in tumour progression has been well characterized, the specific
contribution of the matrix itself is unknown. Furthermore, the mechanisms
enabling normal-not cancer-stroma to provide tumour-suppressive signals and act
as an antitumorigenic barrier are poorly understood. Here we show that
extracellular matrix (ECM) generated by normal fibroblasts (NFs) is softer than
the CAF matrix, and its physical and structural features regulate cancer cell
proliferation. We find that normal ECM triggers downregulation and nuclear exit
of the histone demethylase JMJD1a resulting in the epigenetic growth restriction
of carcinoma cells. Interestingly, JMJD1a positively regulates transcription of
many target genes, including YAP/TAZ (WWTR1), and therefore gene expression in a
stiffness-dependent manner. Thus, normal stromal restricts cancer cell
proliferation through JMJD1a-dependent modulation of gene expression.
PMID- 27488964
TI - Ultrasound elastographic evaluation of the median nerve in hemodialysis with
carpal tunnel syndrome.
AB - PURPOSE: The aim of this study was to compare the elasticity of the median nerve
(MN) between hemodialysis (HD) patients without carpal tunnel syndrome (CTS) and
with CTS, and to evaluate the diagnostic usefulness of the elasticity of the MN
in HD-CTS. MATERIALS AND METHODS: The MN in 22 HD patients without CTS and 49 HD
CTS patients was studied. The cross-sectional area (CSA) and the elasticity of
the MN, which was measured as the subcutaneous fat/median nerve (SF/MN) strain
ratio, were evaluated. RESULTS: The mean SF/MN strain ratio in the groups that
had received hemodialysis for 0-5, >5-10, and >10-15 years was 1.4 +/- 0.28, 1.7
+/- 0.18, and 2.0 +/- 0.67, respectively. The mean CSA of the MN in the three
groups was 9.9 +/- 1.30, 11.6 +/- 1.61, and 13.4 +/- 2.14 mm2, respectively. The
presence of CTS was predicted by means of SF/MN strain ratio and CSA cutoff
values of 1.8 and 11 mm2, respectively. Both the SF/MN strain ratio and the CSA
in the patients with CTS were higher than those in the patients without CTS (P <
0.05). The sensitivity and specificity of the SF/MN strain ratio and CSA of the
MN were 75 and 92 % and 79.2 and 84 %, respectively. CONCLUSION: Sonoelastography
helps to improve the diagnostic accuracy of the ultrasonographic assessment of
CTS.
PMID- 27488965
TI - Short cervix detection in pregnant women by transabdominal sonography with post
void technique.
AB - PURPOSE: This study aimed to evaluate the diagnostic properties of transabdominal
sonography with the post-void technique for cervical length measurement. METHODS:
This study was a prospective cohort study. The inclusion criteria were pregnant
women aged 18-40 years with gestational age of 18-23 completed weeks.
Transabdominal sonography with vertical bladder depth of less than 5 cm and
transvaginal cervical length measurements were carried out by a single
experienced sonographer. RESULTS: There were 307 eligible pregnant women. The
mean age of all subjects was 29.0 years. The mean cervical length obtained
through transabdominal and transvaginal measurement was 3.33 and 3.47 cm,
respectively. Ten patients (3.3 %) were identified as having a short cervix using
transvaginal sonography, and 12 patients (3.9 %) were identified using
transabdominal sonography. CONCLUSION: Transabdominal sonography with vertical
bladder depth of less than 5 cm performed better compared with transvaginal
sonography. It may not be necessary to perform transvaginal sonography if
transabdominal sonography reveals the cervical length to be more than 2.5 cm.
PMID- 27488966
TI - Narrow QRS Tachycardia with RR Alternans: What Is the Mechanism?
PMID- 27488967
TI - For Hospital Readmissions, Hindsight is Not 20/20.
PMID- 27488968
TI - Approaching End-of-Life with Aplomb and Plombage.
PMID- 27488969
TI - Using Adherence Information to Improve Care: From Clinic Visits to Populations.
PMID- 27488971
TI - Capsule Commentary on Goodwin et al., Receipt of Cancer Screening is a Predictor
of Life Expectancy.
PMID- 27488972
TI - The Electrocardiogram Following Dynamic Cardiomyoplasty.
PMID- 27488970
TI - Why Aren't More Primary Care Residents Going into Primary Care? A Qualitative
Study.
AB - BACKGROUND: Workforce projections indicate a potential shortage of up to 31,000
adult primary care providers by the year 2025. Approximately 80 % of internal
medicine residents and nearly two-thirds of primary care internal medicine
residents do not plan to have a career in primary care or general internal
medicine. OBJECTIVE: We aimed to explore contextual and programmatic factors
within primary care residency training environments that may influence career
choices. DESIGN: This was a qualitative study based on semi-structured, in-person
interviews. PARTICIPANTS: Three primary care internal medicine residency programs
were purposefully selected to represent a diversity of training environments.
Second and third year residents were interviewed. APPROACH: We used a survey
guide developed from pilot interviews and existing literature. Three members of
the research team independently coded the transcripts and developed the code
structure based on the constant comparative method. The research team identified
emerging themes and refined codes. ATLAS.ti was used for the analysis. KEY
RESULTS: We completed 24 interviews (12 second-year residents, and 12 third-year
residents). The age range was 27-39 years. Four recurrent themes characterized
contextual and programmatic factors contributing to residents' decision-making:
resident expectations of a career in primary care, navigation of the boundary
between social needs and medical needs, mentorship and perceptions of primary
care, and structural features of the training program. CONCLUSIONS: Addressing
aspects of training that may discourage residents from careers in primary care
such as lack of diversity in outpatient experiences and resident frustration with
their inability to address social needs of patients, and strengthening aspects of
training that may encourage interests in careers in primary care such as
mentorship and protected time away from inpatient responsibilities during primary
care rotations, may increase the proportion of residents enrolled in primary care
training programs who pursue a career in primary care.
PMID- 27488973
TI - HLA-DRB1*16:39, a novel HLA-DRB1*16 variant, discovered in a Taiwanese bone
marrow hematopoietic stem cell donor.
AB - One nucleotide substitution at residue 112 of the HLA-DRB1*16:02:01:01 results in
a novel allele, HLA-DRB1*16:39.
PMID- 27488974
TI - Complex High-Aspect-Ratio Metal Nanostructures by Secondary Sputtering Combined
with Block Copolymer Self-Assembly.
AB - High-resolution (10 nm), high-areal density, high-aspect ratio (>5), and
morphologically complex nanopatterns are fabricated from a single conventional
block copolymer (BCP) structure with a 70 nm scale resolution and an aspect ratio
of 1, through the secondary-sputtering phenomenon during the Ar-ion-bombardment
process. This approach provides a foundation for the design of new routes to BCP
lithography.
PMID- 27488975
TI - Overall and Gender-specific Associations between C-reactive Protein and Stroke
Occurrence: A Cross-sectional Study in US.
PMID- 27488976
TI - Multiple Embolic Infarction Due to a Primary Aortic Intimal Sarcoma.
PMID- 27488977
TI - Imaging Predictors for Atherosclerosis-Related Intracranial Large Artery
Occlusions in Acute Anterior Circulation Stroke.
PMID- 27488978
TI - Extended Use of Hypothermia in Elderly Patients with Malignant Cerebral Edema as
an Alternative to Hemicraniectomy.
AB - BACKGROUND AND PURPOSE: The use of decompressive hemicraniectomy (DHC) for the
treatment of malignant cerebral edema can decrease mortality rates. However, this
benefit is not sufficient to justify its use in elderly patients. We investigated
the effects of therapeutic hypothermia (TH) on safety, feasibility, and
functional outcomes in elderly patients with malignant middle cerebral artery
(MCA) infarcts. METHODS: Elderly patients 60 years of age and older with infarcts
affecting more than two-thirds of the MCA territory were included. Patients who
could not receive DHC were treated with TH. Hypothermia was started within 72
hours of symptom onset and was maintained for a minimum of 72 hours with a target
temperature of 33 degrees C. Modified Rankin Scale (mRS) scores at 3 months
following treatment and complications of TH were used as functional outcomes.
RESULTS: Eleven patients with a median age of 76 years and a median National
Institutes of Health Stroke Scale score of 18 were treated with TH. The median
time from symptom onset to initiation of TH was 30.3+/-23.0 hours and TH was
maintained for a median of 76.7+/-57.1 hours. Shivering (100%) and electrolyte
imbalance (82%) were frequent complications. Two patients died (18%). The mean
mRS score 3 months following treatment was 4.9+/-0.8. CONCLUSIONS: Our results
suggest that extended use of hypothermia is safe and feasible for elderly
patients with large hemispheric infarctions. Hypothermia may be considered as a
therapeutic alternative to DHC in elderly individuals. Further studies are
required to validate our findings.
PMID- 27488979
TI - Neural Stem Cells and Ischemic Brain.
AB - Stroke activates neural stem cells in the ventricular-subventricular zone (V/SVZ)
of the lateral ventricle, which increases neuroblasts and oligodendrocyte
progenitor cells (OPCs). Within the ischemic brain, neural stem cells,
neuroblasts and OPCs appear to actively communicate with cerebral endothelial
cells and other brain parenchymal cells to mediate ischemic brain repair;
however, stroke-induced neurogenesis unlikely plays any significant roles in
neuronal replacement. In this mini-review, we will discuss recent findings how
intercellular communications between stroke-induced neurogenesis and
oligodendrogenesis and brain parenchymal cells could potentially facilitate brain
repair processes.
PMID- 27488981
TI - Prevalence and Characteristics of Unruptured Cerebral Aneurysms in Ischemic
Stroke Patients.
AB - BACKGROUND AND PURPOSE: The prevalence of unruptured cerebral aneurysms (UCAs) in
ischemic stroke patients is not clearly defined. This study aimed to measure the
prevalence and characteristics of UCAs in patients with acute ischemic stroke
(AIS) and to compare our findings with those of the general population. In
addition, we investigated the factors associated with cerebral aneurysms in AIS
patients. METHODS: We retrospectively reviewed the brain magnetic resonance
angiography images of 955 patients with AIS and 2,118 controls who had received a
brain magnetic resonance angiography as part of a health check-up. We
investigated the prevalence, size, location, and risk factors of the subjects in
the context of UCAs. RESULTS: UCAs were found in 74 patients with AIS (7.7%) and
in 79 who received a health check-up (3.7%). The prevalence of UCAs was
significantly higher in the AIS group than in the health check-up group (odds
ratio 2.17, 95% confidence interval 1.56-3.01). The mean aneurysm diameter was
larger in the AIS group than in the health check-up group (3.75 mm vs. 3.02 mm,
P=0.009). UCAs were primarily located in the internal carotid artery in both
groups, and aneurysms in the middle cerebral artery were particularly common in
the AIS group. According to multivariate analysis, hypertension alone was
associated with an increased prevalence of UCAs in stroke patients. CONCLUSIONS:
This study identified a higher prevalence and larger size of UCAs in AIS patients
than in the general population. Hypertension was an independent risk factor of
UCA in AIS.
PMID- 27488980
TI - Association between Aortic Atheroma and Cerebral Small Vessel Disease in Patients
with Ischemic Stroke.
AB - BACKGROUND AND PURPOSE: Cerebral small vessel disease (SVDs) are related with
large artery atherosclerosis. However, the association between aortic atheroma
(AA) and cerebral small vessel disease has rarely been reported. This study
evaluated the relationship between presence and burden of AAs and those of SVDs
in patients with acute ischemic stroke. METHODS: We included 737 consecutive
patients who underwent transesophageal echocardiography (TEE) and brain magnetic
resonance imaging (MRI) for evaluation of acute stroke. AA subtypes were
classified as complex aortic plaque (CAP) and simple aortic plaque (SAP).
Presence and burden of SVDs including cerebral microbleeds (CMBs), white matter
hyperintensities (WMHs), perivascular spaces (PVSs), asymptomatic lacunar
infarctions (ALIs), and total SVD score, were investigated. RESULTS: AA was found
by TEE in 360 (48.8%) patients including 11.6% with CAP and 37.2% with SAP. One
or more types of SVDs was found in 269 (36.4%) patients. In multivariable
analysis, presence of CMBs (odds ratio [OR] 4.68), high-grade WMHs (OR 3.13),
high-grade PVSs (OR 3.35), and ALIs (OR 4.24) were frequent in patients with AA
than those without AA. Each 1-point increase in total SVD score increased the
odds of presence of CAP (OR 1.94, 95% confidence interval (CI) 1.44-1.85) and SAP
(OR 1.54, 95% CI 1.35-1.75). CONCLUSIONS: In this study, patients with AA
frequently had cerebral SVDs. Larger burden of AA was associated with advanced
cerebral SVDs. Our findings give an additional information for positive
relationship with systemic atherosclerosis and coexisting cerebral SVDs in acute
ischemic stroke patients.
PMID- 27488982
TI - Effects of Acute Exposure to Sublethal Waterborne Cadmium on Energy Homeostasis
in Silver Carp (Hypophthalmichthys molitrix).
AB - Effects of acute exposure to sublethal waterborne cadmium (Cd) on energy
homeostasis in filter-feeding fishes have rarely been studied. The response
patterns of energy substances were investigated in juvenile silver carp
(Hypophthalmichthys molitrix) exposed to sublethal waterborne Cd for 96 h. The
results showed the 96hLC50 of Cd on juvenile silver carp was 1.723 mg/L.
Sublethal acute exposure of Cd significantly affected the energy homeostasis of
juvenile silver carp, including increase in plasma glucose and lactate, and
decrease in plasma triglyceride, muscle glycogen and triglyceride and liver
glycogen. The results indicated that glycogen and triglyceride prior to protein
were mobilized to meet the increased demands for detoxication and repair
mechanism to sublethal waterborne Cd exposure, and glycogen level depleted faster
and restored slower in the liver than in the white muscle in juvenile silver
carp.
PMID- 27488983
TI - Simplifying and enhancing the use of PyMOL with horizontal scripts.
AB - Scripts are used in PyMOL to exert precise control over the appearance of the
output and to ease remaking similar images at a later time. We developed
horizontal scripts to ease script development. A horizontal script makes a
complete scene in PyMOL like a traditional vertical script. The commands in a
horizontal script are separated by semicolons. These scripts are edited
interactively on the command line with no need for an external text editor. This
simpler workflow accelerates script development. In using PyMOL, the illustration
of a molecular scene requires an 18-element matrix of view port settings. The
default format spans several lines and is laborious to manually reformat for one
line. This default format prevents the fast assembly of horizontal scripts that
can reproduce a molecular scene. We solved this problem by writing a function
that displays the settings on one line in a compact format suitable for
horizontal scripts. We also demonstrate the mapping of aliases to horizontal
scripts. Many aliases can be defined in a single script file, which can be useful
for applying costume molecular representations to any structure. We also
redefined horizontal scripts as Python functions to enable the use of the help
function to print documentation about an alias to the command history window. We
discuss how these methods of using horizontal scripts both simplify and enhance
the use of PyMOL in research and education.
PMID- 27488985
TI - Antioxidant efficacy of Kalanchoe daigremontiana bufadienolide-rich fraction in
blood plasma in vitro.
AB - CONTEXT: The main source of bufadienolides is toad venom; however, plants such as
members of Kalanchoe Adans. (Crassulaceae) genus may also synthesize these
bioactive substances. OBJECTIVE: This is the first study on antioxidant effects
and cytotoxicity of bufadienolide-rich fraction isolated from Kalanchoe
daigremontiana Raym.-Hamet & H. Perrier. MATERIALS AND METHODS: The methanolic
fraction was extracted from the plant roots and contained 0.48 mg
bufadienolides/mg of dry mass (11alpha,19-dihydroksytelocinobufagin,
bersaldegenin-1-acetate, bersaldegenin-1,3,5-orthoacetate, 19-(acetyloxy)
3beta,5beta,11alpha,14-tetrahydroxyl-12-oxo-bufa-20,22-dienolide and 19
(acetyloxy)-1beta,3beta,5beta,14-tetrahydroxyl-bufa-20,22-dienolide, mainly). The
cytotoxicity of K. daigremontiana fraction was evaluated in an in vitro
experimental model of blood platelets. The viability of blood platelets was
determined on the basis of a release of lactate dehydrogenase. RESULTS: The
fraction scavenged DPPH* radicals, with EC50 of 21.80 MUg/mL. Studies on an
experimental model of blood plasma under peroxynitrite-induced oxidative stress
revealed that the plant preparation had moderate antioxidant properties. Levels
of 3-nitrotyrosine and thiol groups indicated that the protective effect of K.
daigremontiana was significant mainly for its concentration of 50 MUg/mL. No
effect was found in prevention of oxidation of low-molecular plasma thiols
(glutathione, cysteine and cysteinylglycine). Simultaneously, measurements of
lipid hydroperoxides and thiobarbituric acid-reactive substances (TBARS)
indicated that the examined fraction might be effective antioxidant at broader
concentration range, that is 1-5 and 25-50 MUg/mL for hydroperoxides and TBARS
generation, respectively. No cytotoxicity was observed at the concentration range
of 1-50 MUg/mL. CONCLUSIONS: Based on the obtained results, we suggest that
antioxidant activity may additionally contribute to beneficial properties of K.
daigremontiana-derived extracts.
PMID- 27488984
TI - Second-line treatment for metastatic clear cell renal cell cancer: experts'
consensus algorithms.
AB - BACKGROUND: Second-line systemic treatment options for metastatic clear cell
renal cell cancer (mccRCC) are diverse and treatment strategies are variable
among experts. Our aim was to investigate the approach for the second-line
treatment after first-line therapy with a tyrosine kinase inhibitor (TKI).
Recently two phase III trials have demonstrated a potential role for nivolumab
(NIV) and cabozantinib (CAB) in this setting. We aimed to estimate the impact of
these trials on clinical decision making. MATERIALS AND METHODS: Eleven
international experts were asked to provide their treatment strategies for second
line systemic therapy for mccRCC in the current setting and once NIV and CAB will
be approved and available. The treatment strategies were analyzed with the
objective consensus approach. RESULTS: The analysis of the decision trees
revealed everolimus (EVE), axitinib (AXI), NIV and TKI switch (sTKI) as
therapeutic options after first-line TKI therapy in the current situation and
mostly NIV and CAB in the future setting. The most commonly used criteria for
treatment decisions were duration of response, TKI tolerance and zugzwang a
composite of several related criteria. CONCLUSION: In contrast to the first-line
setting, recommendations for second-line systemic treatment of mccRCC among
experts were not as heterogeneous. The agents mostly used after disease
progression on a first-line TKI included: EVE, AXI, NIV and sTKI. In the future
setting of NIV and CAB availability, NIV was the most commonly chosen drug,
whereas several experts identified situations where CAB would be preferred.
PMID- 27488986
TI - MEMORIAL.
PMID- 27488987
TI - Brazilian scale of hearing and language development in children (EDAL-1) with
cochlear implant and less than two years of hearing AGE.
AB - OBJECTIVE: To present the protocol called the Brazilian Scale of Hearing and
Language Development. MATERIALS AND METHODS: This is a protocol developed in
order to assess and record the development of hearing and language skills in
young children who have undergone cochlear implantation during the first two
years of hearing age. It was applied to the parents of 41 children over a period
of 12 months at the cochlear implant clinic in the Pequeno Principe Hospital in
Curitiba, Brazil. Registered were: the time taken to implement the protocol; ease
of understanding the questions; numerical results obtained by the children
evaluated. RESULTS: In general, the questions were considered easy to understand.
The minimum time taken for application of the protocol was two minutes and the
maximum was 11 minutes. At the end of the evaluation, it was possible to quantify
the development in 100% of the cases. CONCLUSIONS: EDAL proved an agile, quick
and easy, instrument to be used in the first two years of hearing age.
PMID- 27488988
TI - Preliminary longitudinal results of neuropsychological education as first and
sole intervention for new tinnitus patients.
AB - INTRODUCTION: Tinnitus is a potentially aggravating symptom without curative
treatment. Cognitive Behavioral Therapy has been proved effective. It aims to
learn to cope with tinnitus by reducing fearfull appraisal of tinnitus. Education
is an important part of that therapy. Neuropsychological education alone in an
early stage of the symptom might reduce the need for extensive therapy.
OBJECTIVE: To evaluate change of tinnitus related handicaps after
neuropsychological education. MATERIALS AND METHODS: One hundred and six new
tinnitus patients without otological ilnesses were educated in a
neurophysiological model of tinnitus after otological inspection and audiometry.
This was organized as a monthly standard session. Primary outcome was the
Tinnitus Handicap Inventory (THI) score and subscores before intervention and 6
weeks after with follow up after 12 months. Seventy four participants were
included for analysis. RESULTS: Six weeks post intervention a trend was seen in
reduction of catastrophic reactions. After 12 months a significant decrease in
THI scores was observed (all p values <= 0.01). The majority received no other
treatment after the education. There were no significant differences between
participants evaluating the workshop positively or negatively with respect to THI
scores or tinnitus severity. CONCLUSION: Neuropsychological education may be a
sufficient intervention for new tinnitus sufferers.
PMID- 27488989
TI - Tinnitus and temporomandibular disorders: the knowledge of professionals for
primary health care in the city of Curitiba.
AB - INTRODUCTION: The high prevalence of temporomandibular disorders and tinnitus
along with the negative effects on the quality of life of affected individuals
makes this association a matter of public health. OBJECTIVE: To assess the
knowledge of primary health care professionals about the interrelationship
between temporomandibular disorders and tinnitus. MATERIALS AND METHODS: This was
a quantitative cross-sectional study, using a structured, self-administered
questionnaire for a group of 54 dental surgeons. The statistical analysis used
involved descriptive analyses through absolute and relative frequency
distributions. RESULTS: The results showed that the professionals do not, as a
routine, examine the temporomandibular joints and masticatory muscles during
physical examination. In addition, there was a low percentage of correct answers
on questions that assess knowledge. CONCLUSIONS: There is a need to inform
dentists about the interrelationship between temporomandibular disorders and
tinnitus. Furthermore, there is a need to encourage managers to establish
teaching and learning tools that support and strengthen the role of dentists in
primary health care. In this way, routine visits might minimize these disorders,
and thus contribute to the quality of life of the population.
PMID- 27488990
TI - The impact of tinnitus on the quality of life in patients with temporomandibular
dysfunction.
AB - INTRODUCTION: The most common otological symptoms in patients with
temporomandibular disorders (TMD) are ear fullness, tinnitus and ear pain.
OBJECTIVE: To evaluate the impact of tinnitus on the quality of life for patients
with TMD. METHOD: This is a quantitative, cross-sectional retrospective study.
The sample consisted of 19 individuals with TMD, 17 (89.47%) females and 2
(10.53%) male, mean age 53.5 years. Data collection consisted of: anamnesis, pure
tone audiometry, acuphenometry and application of the Portuguese version of the
Tinnitus Handicap Inventory (Brazilian THI). RESULTS: 63.12% had had tinnitus for
less than five years, and 15.79% had tinnitus that sounded like whistling, rain
and/or a cricket. There was a predominance of laterality in the right ear
(42.11%). 52.63% of the subjects reported that their tinnitus is continuous,
while 31.58% stated that it lasts for days, and 47.37% report that it is common.
The audiometry revealed mean audiometric thresholds above 25 dB HL in the high
frequencies (3000, 4000, 6000 and 8000 Hz) bilaterally. In acuphenometry, the
average loudness of the tinnitus was 21 dB SL the right ear and 17.85 dB SL in
the left ear, and the average tinnitus pitch was 3775 Hz in the right ear and
3750 Hz in the left ear. The total THI score was 37.8 points. It appears that
there is significant correlation between the THI scale, time of tinnitus duration
and its occurrence. CONCLUSION: Tinnitus reported in patients with TMD caused
moderate impact on quality of life and can be seen in the presence of background
noise although daily activities can still be performed.
PMID- 27488992
TI - Description of tinnitus and its relation to discomfort level in a group of
elderly hearing aid wearers.
AB - INTRODUCTION: Evaluating quality of life for tinnitus patients has been an
interest of several specialties that have seen the negative impact that the
disorder has on people. OBJECTIVE: To assess and qualify tinnitus in a group of
elderly hearing aid wearers. MATERIALS AND METHODS: A descriptive cross-sectional
study involving 53 elderly patients with tinnitus without remission after wearing
hearing aids. All subjects were submitted to: a medical evaluation, an
audiological evaluation, acuphenometry, an investigation of tinnitus annoyance
level and quality of life. RESULTS: There were 20 men and 33 women. The mean age
was 72.5 years. The sample was mostly characterized by having sensorineural
hearing loss (84%), moderate to moderately severe (86%) and downward sloping
(82%). With respect to the description of the tinnitus sound, the most common
were a hissing sound (93%) of average pitch (84%). Regarding the subjects'
perception of tinnitus, it was found that subjects had varying levels of
annoyance: mild (25%), moderate (33%), severe (22%), most severe (20%). Men are
more bothered by tinnitus than women. Most of the sample reported being satisfied
or very satisfied with their quality of life. CONCLUSION: It was possible to
evaluate and qualify tinnitus in the sample. Although tinnitus is a frequent
audiological symptom that interferes in the life of the elderly, in the sample it
did not weigh heavily in terms of quality of life.
PMID- 27488991
TI - Speech language pathology findings in a Treacher Collins syndrome patient.
AB - BACKGROUND: Treacher Collins syndrome (TCS) is a rare disorder with different
levels of severity due to congenital head and face abnormalities which affect
language, orofacial musculature, voice and breadth, suction, chewing and
swallowing functions. AIMS: This paper objectifies to report a Treacher Collins
syndrome patient, describing phonoaudiological changes that can be found in
individuals suffering from this syndrome. METHODS & PROCEDURES: The study was
carried out with a male child at a teaching Speech Language Pathology clinic in
Southern Brazil. The patient underwent audiological assessment, as well as
orofacial motricity, swallowing, voice and speech assessments. OUTCOMES &
RESULTS: By means of the assessments, it was possible to perceive that the
patient presents moderate hearing loss, inadequacy of phonoarticulatory organs,
base of the tongue going backwards and epiglottis collapse over the larynx. In
spite of evidencing significant difficulty in producing speech sounds, due to
musculoskeletal changes, he effectively interacts in communicative situations,
besides understanding sentences and narrated stories. CONCLUSIONS & IMPLICATIONS:
The screened case report evidences that an interdisciplinary follow-up is
indispensable for this patient suffering from Treacher Collins syndrome, which
implies not only speech language therapeutic follow-up, but also in ear, nose and
throat and orthodontics areas.
PMID- 27488993
TI - Amplified music with headphones and its implications on hearing health in teens.
AB - OBJECTIVE: To analyze the habits and behavior of adolescents exposed to amplified
music with headphones and its implications on their hearing health. METHODS: One
hundred thirty-one high school students, aged 15 to 18 years were given a
questionnaire containing closed questions regarding their habits and behavior
related to personal stereos use. It is a descriptive cross-sectional study and
used the Chi-square test. RESULTS: It was shown that 79% of young people make use
of portable music devices, 61.83% have a habit of using them often, 34.35% have
long periods of exposure, and 37.40% use them at high volume. In terms of
symptoms, present were: difficulty concentrating 63.36%; the need to ask people
to repeat what was said 64.12%; the need to increase the TV volume 43.51%;
tinnitus 38.93%, excitability 38.93%; and 36.64% of teens say they are somewhat
worried about losing their hearing through the use of personal stereos. For the
preventive aspects, 90.84% believe that noise is part of society, 80.92% find it
important to reduce noise pollution, 51.91% would like to know the influence of
the noise/pollution, but 74.81% would not like to participate in projects with
questions about hearing health. CONCLUSION: The youths in this study are making
indiscriminate use of personal stereos with headphones, within a population at
risk for hearing loss considering its habits. Hearing Health Promotion Programs
are recommended for this population.
PMID- 27488994
TI - Occurrence of tinnitus and other auditory symptoms among musicians playing
different instruments.
AB - INTRODUCTION: Tinnitus is one of the most reported auditory symptoms among
musicians and can negatively influence their ability to work, sometimes even more
severely than hearing loss. OBJECTIVES: To analyze the occurrence of tinnitus and
other auditory symptoms in musicians who play different instruments. METHODS: One
hundred musicians participated by answering a questionnaire on instrument played,
practice time with the instrument, occurrence of tinnitus, hearing difficulties,
and intolerance to loud sounds. The symptoms were analyzed in relation to gender,
musical instrument, and time of experience using statistical tests such as the
Chi-squared test and Difference in Proportions test at a significance level of
0.05 as well as finding the Prevalence Ratio. RESULTS: Tinnitus was the most
frequent symptom among musicians, especially among those who play amplified
instruments. There was an association between tinnitus and hearing difficulty,
and between instrument experience time and intolerance to loud sounds. The
proportion of musicians with occasional tinnitus was high among those with less
than 15 years of musical practice, and 4.53 times more prevalent in those with
more than 15 years of experience. CONCLUSION: The presence of auditory symptoms,
especially tinnitus, among musicians reinforces the need for implementation of
hearing conservation programs for this profession.
PMID- 27488995
TI - The efficacy of hearing aids for emotional and auditory tinnitus issues.
AB - INTRODUCTION: The use of hearing aids has been one of the strategies to reduce
tinnitus perception and improve sufferers' quality of life when this symptom is
associated to hearing impairment. OBJECTIVE: To assess the remission of emotional
and auditory tinnitus impacts on users of hearing aids. METHODS: It is an
experimental, descriptive study carried out with 17 users of unilateral or
bilateral hearing aids, reporting tinnitus, submitted to otorhinolaryngological
screening, tonal audiometry, logoaudiometry and acoustic imittance testing, who
also answered the Iowa Tinnitus Activities Questionnaire, as well as the Iowa
Tinnitus Handicap Questionnaire. RESULTS: There was significant difference in
tinnitus data scoring before the use of hearing aids and after fitting the
hearing aids. CONCLUSION: Analysis of the results evidences that the use of
hearing aids improves tinnitus patients' quality of life, mainly regarding their
emotional and auditory aspects.
PMID- 27488996
TI - Manifestations of a low-frequency sound of unknown origin perceived worldwide,
also known as "the Hum" or the "Taos Hum".
AB - INTRODUCTION: "The Hum" and "Taos Hum" are the common terms used for an annoying
low-frequency sound of unknown and seemingly mysterious external causes. The Hum
is a phenomenon occurring worldwide that affects approximately 2% of the
population, called hearers or hummers. OBJECTIVE: This study investigates the
different manifestations of the Hum based on questionnaires tailor-made for
hearers, with the aim to demystify this phenomenon. MATERIALS AND METHODS:
Questionnaires completed by 162 hearers were evaluated, with a focus on three
often-reported features: whether their Hum forms beats with external sounds,
whether head rotations remove their Hum, and if air travel produces a time lag
until the Hum reappears. RESULTS AND CONCLUSIONS: The presence of at least one of
the three features is typical of the Hum for 73% hearers. The three features are
statistically significant dependent on each other. Hum-oscillations are typically
influenced by head rotation and by sounds and are most likely located in the
semicircular canals and the cochlea. Therefore, for the majority of hearers, the
Hum may represent a rare form of tinnitus that has nothing to do with external
sounds. The remaining group doesn't experience any feature of a typical hearer.
PMID- 27488998
TI - Acute kidney injury induces hallmarks of polycystic kidney disease.
AB - Acute kidney injury (AKI) and autosomal dominant polycystic kidney disease
(ADPKD) are considered separate entities that both frequently cause renal
failure. Since ADPKD appears to depend on a polycystin-1 (Pc1) or Pc2 dosage
mechanism, we investigated whether slow progression of cystogenesis in two Pkd1
transgenic mouse models can be accelerated with moderate ischemia-reperfusion
injury (IRI). Transient unilateral left ischemic kidneys in both nontransgenic
and transgenic mice reproducibly develop tubular dilatations, cysts, and typical
PKD cellular defects within 3 mo post-IRI. Similar onset and severity of IRI
induced-cystogenesis independently of genotype revealed that IRI is sufficient to
promote renal cyst formation; however, this response was not further amplified by
the transgene in Pkd1 mouse models. The IRI nontransgenic and transgenic kidneys
showed from 16 days post-IRI strikingly increased and sustained Pkd1/Pc1 (>3
fold) and Pc2 (>8-fold) expression that can individually be cystogenic in mice.
In parallel, long-term and important stimulation of hypoxia-inducible factor
1alpha expression was induced as in polycystic kidney disease. While mammalian
target of rapamycin signaling is activated, stimulation of the Wnt pathway, with
markedly increased active beta-catenin and c-Myc expression in IRI renal
epithelium, uncovered a similar regulatory cystogenic response shared by IRI and
ADPKD. Our study demonstrates that long-term AKI induces cystogenesis and cross
talk with ADPKD Pc1/Pc2 pathogenic signaling.
PMID- 27488997
TI - Phosphatase inhibition increases AQP2 accumulation in the rat IMCD apical plasma
membrane.
AB - Vasopressin triggers the phosphorylation and apical plasma membrane accumulation
of aquaporin 2 (AQP2), and it plays an essential role in urine concentration.
Vasopressin, acting through protein kinase A, phosphorylates AQP2. However, the
phosphorylation state of AQP2 could also be affected by the action of protein
phosphatases (PPs). Rat inner medullas (IM) were incubated with calyculin (PP1
and PP2A inhibitor, 50 nM) or tacrolimus (PP2B inhibitor, 100 nM). Calyculin did
not affect total AQP2 protein abundance (by Western blot) but did significantly
increase the abundances of pS256-AQP2 and pS264-AQP2. It did not change pS261
AQP2 or pS269-AQP2. Calyculin significantly enhanced the membrane accumulation
(by biotinylation) of total AQP2, pS256-AQP2, and pS264-AQP2. Likewise,
immunohistochemistry showed an increase in the apical plasma membrane association
of pS256-AQP2 and pS264-AQP2 in calyculin-treated rat IM. Tacrolimus also did not
change total AQP2 abundance but significantly increased the abundances of pS261
AQP2 and pS264-AQP2. In contrast to calyculin, tacrolimus did not change the
amount of total AQP2 in the plasma membrane (by biotinylation and
immunohistochemistry). Tacrolimus did increase the expression of pS264-AQP2 in
the apical plasma membrane (by immunohistochemistry). In conclusion, PP1/PP2A
regulates the phosphorylation and apical plasma membrane accumulation of AQP2
differently than PP2B. Serine-264 of AQP2 is a phosphorylation site that is
regulated by both PP1/PP2A and PP2B. This dual regulatory pathway may suggest a
previously unappreciated role for multiple phosphatases in the regulation of
urine concentration.
PMID- 27488999
TI - Renal phenotype in Bardet-Biedl syndrome: a combined defect of urinary
concentration and dilution is associated with defective urinary AQP2 and UMOD
excretion.
AB - The renal phenotype in Bardet-Biedl syndrome (BBS) is highly variable. The
present study describes renal findings in 41 BBS patients and analyzes the
pathogenesis of hyposthenuria, the most common renal dysfunction. Five of 41
patients (12%) showed an estimated glomerular filtration rate < 60 ml.min-1.1.73
m-2 Urine protein and urine albumin-to-creatinine ratio were over 200 and 30 mg/g
in 9/24 and 7/23 patients, respectively. Four of 41 patients showed no renal
anomalies on ultrasound. Twenty of 34 patients had hyposthenuria in the absence
of renal insufficiency. In all 8 of the hyposthenuric patients studied, dDAVP
failed to elevate urine osmolality (Uosm), suggesting a nephrogenic origin.
Interestingly, water loading (WL) did not result in a significant reduction of
Uosm, indicating combined concentrating and diluting defects. dDAVP infusion
induced a significant increase of plasma Factor VIII and von Willebrand Factor
levels, supporting normal function of the type 2 vasopressin receptor at least in
endothelial cells. While urinary aquaporin 2 (u-AQP2) abundance was not different
between patients and controls at baseline, the dDAVP-induced increased u-AQP2 and
the WL-induced reduction of u-AQP2 were blunted in patients with a combined
concentrating and diluting defect, suggesting a potential role of AQP2 in the
defective regulation of water absorption. Urine Uromodulin excretion was reduced
in all hyposthenuric patients, suggesting a thick ascending limb defect.
Interestingly, renal Na, Cl, Ca, but not K handling was impaired after acute WL
but not at basal. In summary, BBS patients show combined urinary concentration
and dilution defects; a thick ascending limb and collecting duct tubulopathy may
underlie impaired water handling.
PMID- 27489000
TI - Restructuring of Holocentric Centromeres During Meiosis in the Plant Rhynchospora
pubera.
AB - Centromeres are responsible for the correct segregation of chromosomes during
mitosis and meiosis. Holocentric chromosomes, characterized by multiple
centromere units along each chromatid, have particular adaptations to ensure
regular disjunction during meiosis. Here we show by detecting CENH3, CENP-C,
tubulin, and centromeric repeats that holocentromeres may be organized
differently in mitosis and meiosis of Rhynchospora pubera Contrasting to the
mitotic linear holocentromere organization, meiotic centromeres show several
clusters of centromere units (cluster-holocentromeres) during meiosis I. They
accumulate along the poleward surface of bivalents where spindle fibers
perpendicularly attach. During meiosis II, the cluster-holocentromeres are mostly
present in the midregion of each chromatid. A linear holocentromere organization
is restored after meiosis during pollen mitosis. Thus, a not yet described case
of a cluster-holocentromere organization, showing a clear centromere
restructuration between mitosis and meiosis, was identified in a holocentric
organism.
PMID- 27489001
TI - Histone Deacetylases with Antagonistic Roles in Saccharomyces cerevisiae
Heterochromatin Formation.
AB - As the only catalytic member of the Sir-protein gene-silencing complex, Sir2's
catalytic activity is necessary for silencing. The only known role for Sir2's
catalytic activity in Saccharomyces cerevisiae silencing is to deacetylate N
terminal tails of histones H3 and H4, creating high-affinity binding sites for
the Sir-protein complex, resulting in association of Sir proteins across the
silenced domain. This histone deacetylation model makes the simple prediction
that preemptively removing Sir2's H3 and H4 acetyl substrates, by mutating these
lysines to unacetylatable arginines, or removing the acetyl transferase
responsible for their acetylation, should restore silencing in the Sir2 catalytic
mutant. However, this was not the case. We conducted a genetic screen to explore
what aspect of Sir2's catalytic activity has not been accounted for in silencing.
Mutation of a nonsirtuin histone deacetylase, Rpd3, restored Sir-protein-based
silencing in the absence of Sir2's catalytic activity. Moreover, this antagonism
could be mediated by either the large or the small Rpd3-containing complex.
Interestingly, this restoration of silencing appeared independent of any known
histone H3 or H4 substrates of Rpd3 Investigation of Sir-protein association in
the Rpd3 mutant revealed that the restoration of silencing was correlated with an
increased association of Sir proteins at the silencers, suggesting that Rpd3 was
an antagonist of Sir2's function in nucleation of Sir proteins to the silencer.
Additionally, restoration of silencing by Rpd3 was dependent on another sirtuin
family member, Hst3, indicating multiple antagonistic roles for deacetylases in
S. cerevisiae silencing.
PMID- 27489002
TI - Gene and Network Analysis of Common Variants Reveals Novel Associations in
Multiple Complex Diseases.
AB - Genome-wide association (GWA) studies typically lack power to detect genotypes
significantly associated with complex diseases, where different causal mutations
of small effect may be present across cases. A common, tractable approach for
identifying genomic elements associated with complex traits is to evaluate
combinations of variants in known pathways or gene sets with shared biological
function. Such gene-set analyses require the computation of gene-level P-values
or gene scores; these gene scores are also useful when generating hypotheses for
experimental validation. However, commonly used methods for generating GWA gene
scores are computationally inefficient, biased by gene length, imprecise, or have
low true positive rate (TPR) at low false positive rates (FPR), leading to
erroneous hypotheses for functional validation. Here we introduce a new method,
PEGASUS, for analytically calculating gene scores. PEGASUS produces gene scores
with as much as 10 orders of magnitude higher numerical precision than competing
methods. In simulation, PEGASUS outperforms existing methods, achieving up to 30%
higher TPR when the FPR is fixed at 1%. We use gene scores from PEGASUS as input
to HotNet2 to identify networks of interacting genes associated with multiple
complex diseases and traits; this is the first application of HotNet2 to common
variation. In ulcerative colitis and waist-hip ratio, we discover networks that
include genes previously associated with these phenotypes, as well as novel
candidate genes. In contrast, existing methods fail to identify these networks.
We also identify networks for attention-deficit/hyperactivity disorder, in which
GWA studies have yet to identify any significant SNPs.
PMID- 27489003
TI - Extracting patterns of morphometry distinguishing HIV associated
neurodegeneration from mild cognitive impairment via group cardinality
constrained classification.
AB - HIV-Associated Neurocognitive Disorder (HAND) is the most common constellation of
cognitive dysfunctions in chronic HIV infected patients age 60 or older in the
U.S. Only few published methods assist in distinguishing HAND from other forms of
age-associated cognitive decline, such as Mild Cognitive Impairment (MCI). In
this report, a data-driven, nonparameteric model to identify morphometric
patterns separating HAND from MCI due to non-HIV conditions in this older age
group was proposed. This model enhanced the potential for group separation by
combining a smaller, longitudinal data set containing HAND samples with a larger,
public data set including MCI cases. Using cross-validation, a linear model on
healthy controls to harmonize the volumetric scores extracted from MRIs for
demographic and acquisition differences between the two independent, disease
specific data sets was trained. Next, patterns distinguishing HAND from MCI via a
group sparsity constrained logistic classifier were identified. Unlike existing
approaches, our classifier directly solved the underlying minimization problem by
decoupling the minimization of the logistic regression function from enforcing
the group sparsity constraint. The extracted patterns consisted of eight regions
that distinguished HAND from MCI on a significant level while being indifferent
to differences in demographics and acquisition between the two sets. Individually
selecting regions through conventional morphometric group analysis resulted in a
larger number of regions that were less accurate. In conclusion, simultaneously
analyzing all brain regions and time points for disease specific patterns
contributed to distinguishing with high accuracy HAND-related impairment from
cognitive impairment found in the HIV uninfected, MCI cohort. Hum Brain Mapp
37:4523-4538, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27489005
TI - Consumption of Walnuts in Combination with Other Whole Foods Produces
Physiologic, Metabolic, and Gene Expression Changes in Obese C57BL/6J High-Fat
Fed Male Mice.
AB - BACKGROUND: Although a reductionist approach has sought to understand the roles
of individual nutrients and biochemicals in foods, it has become apparent that
there can be differences when studying food components in isolation or within the
natural matrix of a whole food. OBJECTIVE: The objective of this study was to
determine the ability of whole-food intake to modulate the development of obesity
and other metabolic dysfunction in mice fed a high-fat (HF), Western-style
obesogenic diet. To test the hypothesis that an n-3 (omega-3) polyunsaturated
fatty acid-rich food could synergize with other, largely polyphenol-rich foods by
producing greater reductions in metabolic disease conditions, the intake of
English walnuts was evaluated in combination with 9 other whole foods. METHODS:
Eight-week-old male C57Bl/6J mice were fed low-fat (LF; 10% fat) and HF control
diets, along with an HF diet with 8.6% (wt:wt) added walnuts for 9 wk. The HF
control diet contained 46% fat with added sucrose (10.9%, wt:wt) and cholesterol
(1%, wt:wt); the added sucrose and cholesterol were not present in the LF diet.
Other groups were provided the walnut diet with a second whole food-raspberries,
apples, cranberries, tart cherries, broccoli sprouts, olive oil, soy protein, or
green tea. All of the energy-containing whole foods were added at an energy level
equivalent to 1.5 servings/d. Body weights, food intake, and glucose tolerance
were determined. Postmortem, serum lipids and inflammatory markers, hepatic fat,
gene expression, and the relative concentrations of 594 biochemicals were
measured. RESULTS: The addition of walnuts with either raspberries, apples, or
green tea reduced glucose area under the curve compared with the HF diet alone (
93%, -64%, and -54%, respectively, P < 0.05). Compared with HF-fed mice, mice fed
walnuts with either broccoli sprouts or green tea (-49% and -61%, respectively, P
< 0.05) had reduced hepatic fat concentrations. There were differences in global
gene expression patterns related to whole-food content, with many examples of
differences in LF- and HF-fed mice, HF- and walnut-fed mice, and mice fed walnuts
and walnuts plus other foods. The mean +/- SEM increase in relative hepatic
concentrations of the n-3 fatty acids alpha-linolenic acid, eicosapentanoic acid,
and docosapentanoic acid in all walnut-fed groups was 124% +/- 13%, 159% +/- 11%,
and 114% +/- 10%, respectively (P < 0.0001), compared with LF- and HF-fed mice
not consuming walnuts. CONCLUSIONS: In obese male mice, walnut consumption with
an HF Western-style diet caused changes in hepatic fat concentrations, gene
expression patterns, and fatty acid concentrations. The addition of a second
whole food in combination with walnuts produced other changes in metabolite
concentrations and gene expression patterns and other physiologic markers.
Importantly, these substantial changes occurred in mice fed typical amounts of
intake, representing only 1.5 servings each food/d.
PMID- 27489004
TI - Psychological Distress Mediates the Association between Food Insecurity and
Suboptimal Sleep Quality in Latinos with Type 2 Diabetes Mellitus.
AB - BACKGROUND: Evidence increasingly indicates that poor sleep quality is a major
public health concern. Household food insecurity (HFI) disproportionately affects
Latinos and is a novel risk factor for poor sleep quality. Psychological distress
may be a potential mechanism through which HFI affects sleep quality. Sleep, food
insecurity, and distress are linked to type 2 diabetes mellitus. OBJECTIVES: We
examined the relations between HFI, psychological distress, and sleep quality and
tested whether psychological distress mediates the relation between HFI and sleep
in people with diabetes mellitus. METHODS: Latinos with type 2 diabetes mellitus
(n = 121) who completed baseline assessments for the CALMS-D (Community Health
Workers Assisting Latinos Manage Stress and Diabetes) stress management
intervention trial completed the US Household Food Security Survey, and measures
of depressive symptoms [Personal Health Questionnaire Depression Scale (PHQ-8)],
anxiety symptoms [Patient-Reported Outcomes Measurement Information System
(PROMIS)-short], diabetes distress [Problem Areas in Diabetes Questionnaire (PAID
5)], and sleep quality [Pittsburgh Sleep Quality Index (PSQI)]. Psychological
distress was operationalized with the PHQ-8, PROMIS-short, and PAID-5 scales. We
used unadjusted and adjusted indirect effect tests with bias-corrected
bootstrapped 95% CIs on 10,000 samples to test both relations between variables
and potential mediation. RESULTS: Mean age was 61 y, 74% were women, and 67% were
food insecure. Experiencing HFI was associated with both greater psychological
distress and worse sleep quality (P < 0.05). Depressive symptoms (adjusted R2:
2.22, 95% CI: 1.27, 3.42), anxiety symptoms (adjusted R2: 1.70, 95% CI: 0.87,
2.85), and diabetes mellitus distress (adjusted R2: 0.60, 95% CI: 0.11, 1.32)
each mediated the relation between HFI and worse sleep quality with and without
adjustment for age, education, income, marital status, and employment status.
CONCLUSIONS: Household food insecurity is a common and potent household stressor
that is associated with suboptimal sleep quality through psychological distress.
Efforts to improve food security and decrease psychological distress may yield
improved sleep in this high-risk population. The CALMS-D stress management trial
was registered at clinicaltrials.gov as NCT01578096.
PMID- 27489006
TI - Hedonic Hunger Is Related to Increased Neural and Perceptual Responses to Cues of
Palatable Food and Motivation to Consume: Evidence from 3 Independent
Investigations.
AB - BACKGROUND: The Power of Food Scale (PFS) seeks to identify individuals who
experience high appetitive drive in response to food cues, which is a construct
termed "hedonic hunger." OBJECTIVE: The purpose of this study was to assess cross
sectional correlates and predictive power of PFS scores to probe the construct of
hedonic hunger. METHODS: Separate data from 3 studies (study 1, n = 44; study 2,
n = 398; study 3, n = 100) were used to evaluate the construct of hedonic hunger.
We examined the correlations between the PFS and neural responsivity during
intake and anticipated intake of palatable foods, behavioral food reinforcement,
perceptual hedonic ratings of food images, and change in body mass index (BMI)
and binge eating over time. RESULTS: Hedonic hunger was strongly related to
bilateral brain response in regions implicated in oral somatosensory processing
during cue-elicited anticipation of food intake (study 1; right postcentral
gyrus: r = 0.67, P < 0.001; left postcentral gyrus: r = 0.64, P < 0.001), and was
correlated with behavioral food reinforcement (study 2; r = 0.31, P = 0.03) and
perceptual hedonic ratings (study 3; r = 0.24, P = 0.02). Hedonic hunger was not
associated with baseline BMI (studies 1-3: P = 0.14, 0.21, and 0.37,
respectively) or change in BMI over the 2-y follow-up (studies 1 and 2: P = 0.14
and 0.37, respectively) but was significantly correlated with baseline binge
eating in 2 samples (study 1: r = 0.58, P = 0.001; study 2: r = 0.31, P = 0.02;
and study 3: P = 0.02). CONCLUSIONS: Hedonic hunger was not predictive of weight
regulation. However, individuals who report high hedonic hunger are likely to
show increased neural and perceptual responses to cues of palatable foods,
increased motivation to consume such foods, and a greater likelihood of current
binge eating.
PMID- 27489007
TI - Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total
Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the
Norwegian Mother and Child Cohort Study.
AB - BACKGROUND: Postnatal administration of caffeine may reduce the risk of cerebral
palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal
caffeine exposure remains unknown. OBJECTIVE: We investigated the association of
intake of caffeine by pregnant women and risk of CP in their children. METHODS:
The study was based on The Norwegian Mother and Child Cohort Study, comprising
>100,000 live-born children, of whom 222 were subsequently diagnosed with CP.
Mothers reported their caffeine consumption in questionnaires completed around
pregnancy week 17 (102,986 mother-child pairs), week 22 (87,987 mother-child
pairs), and week 30 (94,372 mother-child pairs). At week 17, participants were
asked about present and prepregnancy consumption. We used Cox regression models
to estimate associations between exposure [daily servings (1 serving = 125 mL) of
caffeinated coffee, tea, and soft drinks and total caffeine consumption] and CP
in children, with nonconsumers as the reference group. Models included adjustment
for maternal age and education, medically assisted reproduction, and smoking, and
for each source of caffeine, adjustments were made for the other sources.
RESULTS: Total daily caffeine intake before and during pregnancy was not
associated with CP risk. High consumption (>=6 servings/d) of caffeinated soft
drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95%
CI: 1.2, 3.1), and children of women consuming 3-5 daily servings of caffeinated
soft drinks during pregnancy weeks 13-30 also had an increased CP risk (HR: 1.7;
95% CI: 1.1, 2.8). A mean daily consumption of 51-100 mg caffeine from soft
drinks during the first half of pregnancy was associated with a 1.9-fold
increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6). CONCLUSIONS:
Maternal total daily caffeine consumption before and during pregnancy was not
associated with CP risk in children. The observed increased risk with caffeinated
soft drinks warrants further investigation.
PMID- 27489008
TI - Coffee Drinking Is Widespread in the United States, but Usual Intake Varies by
Key Demographic and Lifestyle Factors.
AB - BACKGROUND: Despite widespread popularity and possible health effects, the
prevalence and distribution of coffee consumption in US adults are poorly
characterized. OBJECTIVE: We sought to estimate usual daily coffee intakes from
all coffee-containing beverages, including decaffeinated and regular coffee,
among US adults according to demographic, socioeconomic, and health-related
factors. METHODS: Dietary intake data from <=2 nonconsecutive 24-h dietary
recalls and a food-frequency questionnaire administered during the NHANES 2003
2006 were used to estimate the person-specific probability of consuming coffee on
a particular day and the usual amount consumed on consumption days. Trends in
population mean coffee consumption over time were evaluated by using multiple
linear regression and 1-d 24-h recall data from NHANES 2003-2012. Analyses were
weighted to be representative of the US adult population aged >=20 y. RESULTS: An
estimated 154 million adults, or 75% of the US population, aged >=20 y reported
drinking coffee; 49% reported drinking coffee daily. Prevalence did not vary by
sex, education, income, or self-reported general health (all P >= 0.05) but did
vary by age, race/ethnicity, smoking status, and alcohol drinking (all P < 0.05).
Among coffee drinkers, the mean +/- SE usual intake was 14.1 +/- 0.5 fluid
ounces/d (417 +/- 15 mL/d). Mean usual intakes were higher in men than women, in
older age groups than in those aged 20 to <30 y, in non-Hispanic whites than in
non-Hispanic blacks or Hispanic/other races, in smokers than in never smokers,
and in daily alcohol consumers than in nonconsumers (all P < 0.05). Population
mean coffee consumption was stable from 2003 to 2012 (P-trend = 0.09).
CONCLUSIONS: Coffee is widely consumed in the United States, with usual intakes
varying by lifestyle and demographic factors, most notably by age. Longitudinal
studies are needed to determine whether observed differences by age reflect birth
cohort effects or changes in drinking patterns over the lifetime.
PMID- 27489010
TI - Prolonged Exclusive Breastfeeding Duration Is Positively Associated with Risk of
Anemia in Infants Aged 12 Months.
AB - BACKGROUND: The association between exclusive breastfeeding duration and infant
anemia is not clear. OBJECTIVE: This study aimed to assess the association of
exclusive breastfeeding duration with risk of anemia in infants at 12 mo of age
and in children aged 48-71 mo in mainland China. METHODS: Detailed breastfeeding
information and anthropometric data were obtained for 65,256 children enrolled in
the Jiaxing Birth Cohort at 1, 3, and 6 mo of age. Hemoglobin was measured in
25,549 children at 12 mo and in 32,770 children between the ages of 48 and 71 mo.
Anemia was defined as hemoglobin concentrations <110 g/L in children aged <60 mo
and <115 g/L in children aged >=60 mo. The associations between exclusive
breastfeeding duration and risk of anemia were assessed as adjusted ORs by using
multiple logistic regression. RESULTS: Overall anemia prevalences at 12 and 48-71
mo were 24.9% and 9.9%, respectively. Exclusive breastfeeding for >=6 mo, but not
for 3-5 mo, was significantly associated with a higher risk of anemia in infants
at age 12 mo (OR: 1.15; 95% CI: 1.02, 1.29; P = 0.02) compared with exclusive
breastfeeding for <3 mo. For young children aged 48-71 mo, this finding was only
marginally significant (OR: 1.13; 95% CI: 0.99, 1.29; P = 0.08). Prolonged
duration of exclusive breastfeeding was also significantly associated with
decreased hemoglobin concentrations of -0.56 g/L (95% CI: -1.10, -0.03; P = 0.04)
in infants and -0.99 g/L (95% CI: -1.44, -0.55; P < 0.001) in young children.
CONCLUSIONS: Exclusive breastfeeding for >=6 mo was associated with an increased
risk of anemia in infants aged 12 mo and with lower hemoglobin concentrations in
both infants aged 12 mo and young children aged 48-71 mo. Parents should provide
infants with an adequate source of iron after 6 mo of exclusive breastfeeding.
PMID- 27489009
TI - Serum Immune System Biomarkers Neopterin and Interleukin-10 Are Strongly Related
to Tryptophan Metabolism in Healthy Young Adults.
AB - BACKGROUND: Changes in tryptophan metabolism through the vitamin B-6-dependent
kynurenine pathway have been linked to activation of the immune system.
OBJECTIVE: We hypothesized that blood concentrations of tryptophan and its
catabolites were associated with biomarkers relevant to inflammatory processes in
healthy noninflamed subjects. METHODS: Healthy young adults (n = 737) aged 18-28
y without any known diseases or clinical evidence of inflammation provided blood
samples for analysis of serum tryptophan/kynurenine metabolites, neopterin, C
reactive protein (CRP), and plasma pyridoxal 5'-phosphate (PLP) with LC-tandem
mass spectrometry methodologies. A panel of cytokines was measured in serum by
using high-sensitivity ELISA assays. Anthropometric and lifestyle data were
collected by questionnaire. Multiple linear regression analysis to determine the
effect of measured serum cytokine concentrations as predictors of tryptophan
metabolites was performed on inverse normal-rank transformations of the data,
adjusted for sex, body mass index, smoking, alcohol intake, and contraceptive use
in women. RESULTS: Median serum CRP and neopterin concentrations were well below
established clinical cutoffs for inflammation. We observed significant positive
associations between serum interleukin-10 (IL-10) and serum kynurenine (P =
0.0002), the kynurenine-to-tryptophan ratio (KTR) (P = 0.003), 3
hydroxykynurenine (P = 0.01), and 3-hydroxyanthranilic acid (P = 0.04). Serum
neopterin was positively associated with kynurenine, the KTR (both P < 0.0001),
and anthranilic acid (P = 0.004), and was negatively associated with serum
tryptophan (P = 0.01) and PLP (P < 0.0001). Serum tumor necrosis factor alpha was
also negatively associated with tryptophan (P < 0.001). CONCLUSIONS: In healthy
young adults with no apparent inflammatory conditions, serum tryptophan
metabolites are significantly associated with key immune system biomarkers. The
observed association between IL-10 and kynurenine is unexpected and suggests that
kynurenine-linked mechanisms promoting negative regulation of inflammatory
responses are associated with normal immune homeostasis.
PMID- 27489011
TI - Comparison of Preventive and Therapeutic Zinc Supplementation in Young Children
in Burkina Faso: A Cluster-Randomized, Community-Based Trial.
AB - BACKGROUND: The WHO and UNICEF recommend therapeutic zinc supplementation (TZS)
for the treatment of diarrhea. In zinc-deficient populations, preventive zinc
supplementation might provide greater benefits for reducing diarrhea and malaria
incidence and increasing growth and plasma zinc (pZn) concentration. If
effective, intermittent preventive zinc supplementation (IPZS) would cost less
than daily preventive zinc supplementation (DPZS). OBJECTIVE: We assessed the
effects of IPZS, DPZS, and TZS in children on the primary outcomes of diarrhea
incidence, malaria incidence, growth, and pZn concentration compared with
nonsupplemented control groups. METHODS: Rural Burkinabe children (n = 7641; 6-30
mo old) in 36 clusters were randomly assigned to 1 of 5 treatment groups for 16,
32, or 48 wk: 1) IPZS (10 mg Zn/d for 10 d every 16 wk); 2) DPZS (7 mg Zn/d); 3)
TZS (20 mg Zn/d for 10 d for diarrhea); 4) morbidity surveillance control (MSC);
or 5) nonintervention control (NIC). Supplemented groups remained masked until
completion of primary analyses with mixed models. RESULTS: At baseline, stunting
(28.6%) and low pZn concentration (<65 MUg/dL; 43.5%) were common. After 48 wk,
mean +/- SE pZn increased more (P = 0.008) in the DPZS group (3.9 +/- 1.3 MUg/dL)
than in the TZS (-0.5 +/- 1.2 MUg/dL) and NIC (-1.2 +/- 0.9 MUg/dL) groups. All
supplemented groups had a moderately lower incidence of reported diarrhea (0.48
0.49 compared with 0.57 episodes/100 d, P = 0.001) and reported fever (1.1-1.2
compared with 1.5 episodes/100d, P < 0.001) and gained slightly less length (3.15
3.20 compared with 3.36 cm/16 wk, P < 0.001) than the MSC group, but did not
differ from each other. Prevalence of diarrhea and incidences of confirmed fever
and malaria were not different across study groups. CONCLUSIONS: The preventive
and TZS groups had reduced diarrhea incidence, but it is uncertain whether this
resulted from a functional response to zinc or reporting bias. The comparison
should be re-examined in populations known to respond to zinc supplementation.
This trial was registered at www.clinicaltrials.gov as NCT00944359.
PMID- 27489012
TI - Erratum to: A novel procedure on next generation sequencing data analysis using
text mining algorithm.
PMID- 27489013
TI - Renal fossa recurrence after nephrectomy for renal cell carcinoma: prognostic
features and oncological outcomes.
AB - OBJECTIVES: To describe the clinicopathological features associated with
increased risk of renal fossa recurrence (RFR) after radical nephrectomy (RN) and
to describe the prognostic features associated with cancer-specific survival
(CSS) among patients with RFR treated with primary locally directed therapy,
systemically directed therapy or expectant management. PATIENTS AND METHODS: The
records of 2 502 patients treated with RN for unilateral, sporadic, localized
renal cell carcinoma (RCC) between 1970 and 2006 were reviewed. CSS after RFR was
estimated using the Kaplan-Meier method. Associations with the development of RFR
and CSS after RFR were evaluated using Cox proportional hazards regression
models. RESULTS: A total of 33 (1.3%) patients developed isolated RFR (iRFR) and
30 (1.2%) patients developed RFR in the setting of synchronous metastases after
RN (study cohort, N = 63). The median follow-up for the series was 9.0 years
after RN and 6.0 years after RFR diagnosis. On multivariable analysis, advanced
pathological stage (pT2: hazard ratio [HR] 4.36, P = 0.004; pT3/4: HR 4.39, P =
0.003) and coagulative necrosis (HR 2.71, P = 0.006) were independently
associated with increased risk of iRFR. The median time to recurrence was 1.5
years after RN among the 33 patients with iRFR, and 1.4 years among all patients.
Overall, the median CSS was 2.5 years after diagnosis of iRFR, 1.3 years after
RFR in the setting of synchronous metastases, and 2.2 years overall. After
primary locally directed therapy (surgery, ablation or radiation), systemic
therapy or expectant management, the 3-year CSS rates among patients with iRFR
were 63%, 50% and 13% (P = 0.001) and were 64%, 50% and 28% (P = 0.006) among all
patients, respectively. On multivariable analysis, when compared with
observation, locally directed therapies were associated with a significantly
decreased risk of death from RCC (HR 0.26, P < 0.001). CONCLUSIONS: Renal fossa
recurrence is a rare event after RN for RCC and portends a poor prognosis, even
in the absence of synchronous metastases. Development of iRFR is associated with
advanced stage and aggressive tumour biology. Patients who underwent primary
locally directed therapy had superior CSS compared with those treated with
expectant management, supporting the use of aggressive local treatment in
carefully selected patients with RFR. Future research is needed to determine the
optimum role and sequencing of combined therapy in patients with this rare
entity.
PMID- 27489014
TI - Genomic validation of the differential preservation of population history in
modern human cranial anatomy.
AB - OBJECTIVES: In modern humans, the significant correlation between neutral genetic
loci and cranial anatomy suggests that the cranium preserves a population history
signature. However, there is disagreement on whether certain parts of the cranium
preserve this signature to a greater degree than other parts. It is also unclear
how different quantitative measures of phenotype affect the association of
genetic variation and anatomy. Here, we revisit these matters by testing the
correlation of genetic distances and various phenotypic distances for ten modern
human populations. MATERIALS AND METHODS: Geometric morphometric shape data from
the crania of adult individuals (n = 224) are used to calculate phenotypic PST ,
Procrustes, and Mahalanobis distances. We calculate their correlation to neutral
genetic distances, FST , derived from single nucleotide polymorphisms (SNPs). We
subset the cranial data into landmark configurations that include the
neurocranium, the face, and the temporal bone in order to evaluate whether these
cranial regions are differentially correlated to neutral genetic variation.
RESULTS: Our results show that PST , Mahalanobis, and Procrustes distances are
correlated with FST distances to varying degrees. They indicate that overall
cranial shape is significantly correlated with neutral genetic variation. Of the
component parts examined, PST distances for both the temporal bone and the face
have a stronger association with FST distances than the neurocranium. When
controlling for population divergence time, only the whole cranium and the
temporal bone have a statistically significant association with FST distances.
DISCUSSION: Our results confirm that the cranium, as a whole, and the temporal
bone can be used to reconstruct modern human population history.
PMID- 27489015
TI - Trans-oral fine needle aspiration cytology in cervical (C1 and C2) vertebral
lesions: a novel diagnostic approach.
AB - OBJECTIVE: Fine needle aspiration (FNA) cytology is a relatively non-invasive
method for diagnosing both superficial and deep-seated neoplastic and non
neoplastic lesions. In this study, we evaluated the diagnostic utility of trans
oral FNA in cervical (C1 and C2) vertebral and paravertebral lesions. MATERIAL
AND METHODS: Eighteen FNA cases of cervical vertebral and paravertebral lesions
performed by a trans-oral route without any image-guidance between 1995 and 2014
were retrieved from the archives of the cytology department at PGIMER, Chandigarh
and reviewed. RESULTS: Out of 18 cases, a definite diagnosis was given in 15
cases (83.3%). The commonest diagnosis seen was granulomatous inflammation
consistent with tuberculosis (33.3%). CONCLUSION: Trans-oral FNA is a quick,
inexpensive and relatively safe outpatient procedure for sampling C1 and C2
vertebral and paravertebral lesions, which are clinically and radiologically
difficult to approach. It helps in the early diagnosis and management of these
patients.
PMID- 27489016
TI - Connecting Education to Quality: Engaging Medical Students in the Development of
Evidence-Based Clinical Decision Support Tools.
AB - PROBLEM: Evidence-based practice (EBP) skills are crucial for delivering high
quality patient care. It is essential that medical students learn EBP concepts
through a practical, in-depth research project. To date, literature on preparing
students in this manner is limited. APPROACH: In academic year 2014-2015, the
Medical University of South Carolina's (MUSC's) Center for Evidence-Based
Practice (now known as the Value Institute) partnered with College of Medicine
faculty to revitalize the undergraduate medical student EBP curriculum. Without
adding to the number of the lecture hours, the curriculum was restructured to be
more process driven, project based, and clinically relevant. The resulting
yearlong EBP course partnered small teams of medical students with
interprofessional clinical teams to engage the students in developing evidence
based clinical decision support tools. OUTCOMES: The content developed during the
EBP projects is currently being used to develop evidence-based clinical practice
guidelines and accompanying order sets. NEXT STEPS: It is likely that this model
will serve as a new framework for guideline development and will greatly expand
the breadth of evidence-based content currently produced and available for
clinicians at the MUSC. It would be feasible to offer a similar course within the
MUSC to other disciplines and colleges, or at other institutions, if there were
support from administration, interest on the part of clinicians and medical
faculty, and individuals with the required expertise available to develop the
curriculum and facilitate the course. It is worth considering how to improve the
course and evaluating opportunities to implement it within other settings.
PMID- 27489017
TI - Choosing Wisely for Medical Education: Six Things Medical Students and Trainees
Should Question.
AB - PROBLEM: Physician behaviors that promote overuse of health care resources
develop early in training, and the medical education environment helps foster
such behaviors. The authors describe the development of a Choosing Wisely list
for medical students aimed at helping to curb overuse. APPROACH: The list was
developed in 2015 by Choosing Wisely Canada (CWC) in partnership with the
Canadian Federation of Medical Students and the Federation medicale etudiante du
Quebec, which together represent all medical students in Canada. CWC convened a
student-led taskforce to develop recommendations targeting medical student
behaviors with respect to resource stewardship practices. Students at all 17
Canadian medical schools were consulted via an online questionnaire to solicit
feedback on a list of 10 candidate recommendations. The taskforce used this
student feedback in finalizing the list. OUTCOMES: The final list of "Six Things
That Medical Students and Trainees Should Question" highlights both behaviors
students should avoid (e.g., "Don't suggest ordering the most invasive test
before considering other less invasive options") and behaviors related to aspects
of medical training that may promote overuse, such as the hierarchical nature of
clinical supervision (e.g., "Don't hesitate to ask for clarification on tests,
treatments, or procedures that you believe may be ordered inappropriately").
Based on student requests for illustrative examples, clinical vignettes were
developed. NEXT STEPS: This list highlights medical student behaviors and aspects
of the academic environment that drive overuse. It is also relevant to faculty,
whose behaviors and supervision practices influence trainees.
PMID- 27489018
TI - The Impact of Project ECHO on Participant and Patient Outcomes: A Systematic
Review.
AB - PURPOSE: Project Extension for Community Healthcare Outcomes (ECHO) uses tele
education to bridge knowledge gaps between specialists at academic health centers
and primary care providers from remote areas. It has been implemented to address
multiple medical conditions. The authors examined evidence of the impact of all
Project ECHO programs on participant and patient outcomes. METHOD: The authors
searched PubMed, MEDLINE, EMBASE, PsycINFO, and ProQuest from January 2000 to
August 2015 and the reference lists of identified reviews. Included studies were
limited to those published in English, peer-reviewed articles or indexed
abstracts, and those that primarily focused on Project ECHO. Editorials,
commentaries, gray literature, and non-peer-reviewed articles were excluded. The
authors used Moore's evaluation framework to organize study outcomes for quality
assessment. RESULTS: The authors identified 39 studies describing Project ECHO's
involvement in addressing 17 medical conditions. Evaluations of Project ECHO
programs generally were limited to outcomes from Levels 1 (number of
participants) to 4 (providers' competence) of Moore's framework (n = 22 studies,
with some containing data from multiple levels). Studies also suggested that
Project ECHO changed provider behavior (n = 1), changed patient outcomes (n = 6),
and can be cost-effective (n = 2). CONCLUSIONS: Project ECHO is an effective and
potentially cost-saving model that increases participant knowledge and patient
access to health care in remote locations, but further research examining its
efficacy is needed. Identifying and addressing potential barriers to Project
ECHO's implementation will support the dissemination of this model as an
education and practice improvement initiative.
PMID- 27489019
TI - Predictors of community-associated Staphylococcus aureus, methicillin-resistant
and methicillin-susceptible Staphylococcus aureus skin and soft tissue infections
in primary-care settings.
AB - Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become
increasingly common in the outpatient setting; however, risk factors for
differentiating methicillin-resistant S. aureus (MRSA) and methicillin
susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic
treatment decisions. We performed a case-case-control study within 14 primary
care clinics in South Texas from 2007 to 2015. Overall, 325 patients [S. aureus
SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA
SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150)]
were evaluated. Each case group was compared to the control group, and then
qualitatively contrasted to identify unique risk factors associated with S.
aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs [adjusted odds ratio (aOR)
7.60, 95% confidence interval (CI) 3.31-17.45], male gender (aOR 1.74, 95% CI
1.06-2.85), and absence of healthcare occupation status (aOR 0.14, 95% CI 0.03
0.68) were independently associated with S. aureus SSTIs. The only unique risk
factor for community-associated (CA)-MRSA SSTIs was a high body weight (?110 kg)
(aOR 2.03, 95% CI 1.01-4.09).
PMID- 27489020
TI - Outcomes in Diabetic Patients Undergoing Orbital Atherectomy System.
AB - OBJECTIVES: We evaluated the angiographic and clinical outcomes of orbital
atherectomy to treat severely calcified coronary lesions in diabetic and non
diabetic patients. BACKGROUND: Diabetics have increased risk for death,
myocardial infarction, and target vessel revascularization after percutaneous
coronary intervention. Severely calcified coronary lesions are associated with
increased cardiac events. Orbital atherectomy facilitates stent delivery and
optimizes stent expansion by modifying severely calcified plaque. Outcomes in
diabetic patients who undergo orbital atherectomy have not been reported.
METHODS: Our retrospective multicenter registry included 458 consecutive real
world patients with severely calcified coronary arteries who underwent orbital
atherectomy. The primary safety endpoint was the rate of major adverse cardiac
and cerebrovascular events at 30 days. RESULTS: Diabetics represented 42.1%
(193/458) of the entire cohort. The primary endpoint was similar in diabetics and
non-diabetics (1.0% vs. 3.0%%, P = 0.20), as were 30-day rates of death (0.5% vs.
1.9%, P = 0.41), myocardial infarction (0.5% vs. 1.5%, P = 0.40), target vessel
revascularization (0% vs. 0%, P = 1), and stroke (0% vs. 0.4%, P > 0.9).
Angiographic complications and stent thrombosis rate were low and did not differ
between the 2 groups. CONCLUSION: Diabetics represented a sizeable portion of
patients who underwent orbital atherectomy. Diabetics who had severely calcified
coronary arteries and underwent orbital atherectomy had low event rates that were
similar to non-diabetics. Orbital atherectomy appears to be a viable treatment
strategy for diabetic patients. Randomized trials with longer-term follow-up are
needed to determine the ideal treatment strategy for diabetics.
PMID- 27489021
TI - Service quality and patient experiences of ambulatory care in a specialized
clinic vs. a general hospital.
AB - OBJECTIVES: Health care organizations are constantly looking for ways to
establish a differential advantage to attract customers. To this end, service
quality has become an important differentiator in the strategy of health care
organizations. In this study, we compared the service quality and patient
experience in an ambulatory care setting of a physician-owned specialized
facility with that of a general hospital. METHOD: A comparative case study with a
mixed method design was employed. Data were gathered through a survey on health
service quality and patient experience, completed with observations,
walkthroughs, and photographic material. RESULTS: Service quality and patient
experiences are high in both the investigated health care facilities. A
significant distinction can be made between the two facilities in terms of
interpersonal quality (p = 0.001) and environmental quality (P <= 0.001), in
favor of the medical center. The difference in environmental quality is also
indicated by the scores given by participants who had been in both facilities.
Qualitative analysis showed higher administrative quality in the medical center.
Environmental quality and patient experience can predict the interpersonal
quality; for environmental quality, interpersonal quality and age are significant
predictors. CONCLUSIONS: Service quality and patient experiences are high in both
facilities. The medical center has higher service quality for interpersonal and
environmental service quality and is more process-centered.
PMID- 27489022
TI - Premedication with Clarithromycin Is Effective against Secondary Bacterial
Pneumonia during Influenza Virus Infection in a Pulmonary Emphysema Mouse Model.
AB - Secondary bacterial pneumonia (SBP) during influenza increases the severity of
chronic obstructive pulmonary disease (COPD) and its associated mortality.
Macrolide antibiotics, including clarithromycin (CAM), are potential treatments
for a variety of chronic respiratory diseases owing to their pharmacological
activities, in addition to antimicrobial action. We examined the efficacy of CAM
for the treatment of SBP after influenza infection in COPD. Specifically, we
evaluated the effect of CAM in elastase-induced emphysema mice that were
inoculated with influenza virus (strain A/PR8/34) and subsequently infected with
macrolide-resistant Streptococcus pneumoniae CAM was administered to the
emphysema mice 4 days prior to influenza virus inoculation. Premedication with
CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae
inoculation. Survival rates were higher in emphysema mice than control mice.
While CAM premedication did not affect viral titers or exert antibacterial
activity against S. pneumoniae in the lungs, it enhanced host defense and reduced
inflammation, as evidenced by the significant reductions in total cell and
neutrophil counts and interferon (IFN)-gamma levels in bronchoalveolar lavage
fluid and lung homogenates. These results suggest that CAM protects against SBP
during influenza in elastase-induced emphysema mice by reducing IFN-gamma
production, thus enhancing immunity to SBP, and by decreasing neutrophil
infiltration into the lung to prevent injury. Accordingly, CAM may be an
effective strategy to prevent secondary bacterial pneumonia in COPD patients in
areas in which vaccines are inaccessible or limited.
PMID- 27489023
TI - CIB1 and CIB2 are HIV-1 helper factors involved in viral entry.
AB - HIV-1 relies on the host-cell machinery to accomplish its replication cycle, and
characterization of these helper factors contributes to a better understanding of
HIV-host interactions and can identify potential novel antiviral targets. Here we
explored the contribution of CIB2, previously identified by RNAi screening as a
potential helper factor, and its homolog, CIB1. Knockdown of either CIB1 or CIB2
strongly impaired viral replication in Jurkat cells and in primary CD4+ T
lymphocytes, identifying these proteins as non-redundant helper factors.
Knockdown of CIB1 and CIB2 impaired envelope-mediated viral entry for both for X4
and R5-tropic HIV-1, and both cell-free and cell-associated entry pathways were
affected. In contrast, the level of CIB1 and CIB2 expression did not influence
cell viability, cell proliferation, receptor-independent viral binding to the
cell surface, or later steps in the viral replication cycle. CIB1 and CIB2
knockdown was found to reduce the expression of surface molecules implicated in
HIV-1 infection, including CXCR4, CCR5 and integrin alpha4beta7, suggesting at
least one mechanism through which these proteins promote viral infection. Thus,
this study identifies CIB1 and CIB2 as host helper factors for HIV-1 replication
that are required for optimal receptor-mediated viral entry.
PMID- 27489025
TI - Erratum to: Opening Skinner's Box: an Introduction.
AB - [This corrects the article DOI: 10.1007/s40614-014-0016-z.].
PMID- 27489026
TI - A N-heterocyclic tetracarbene Pd(ii) moiety containing a Pd(ii)-Pb(ii) bimetallic
MOF for three-component cyclotrimerization via benzyne.
AB - A novel Pd(ii)-Pb(ii) bimetallic metal-organic framework Pd(ii)-Pb(ii)-MOF (B)
which contains an N-heterocyclic tetracarbene Pd(ii) moiety was synthesized based
on a chelating N-heterocyclic dicarbene Pd(ii)-NHDC ligand (A) under solvothermal
conditions. It can be a highly active heterogeneous catalyst for three-component
cyclotrimerization via benzyne species.
PMID- 27489024
TI - Ethanol modulates facial stimulation-evoked outward currents in cerebellar
Purkinje cells in vivo in mice.
AB - Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and
cerebellar ataxia. In this study, we investigated the effect of ethanol on facial
stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells
(PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under
voltage-clamp conditions, ethanol (300 mM) decreased the amplitude, half-width,
rise time and decay time of facial stimulation-evoked outward currents in PCs.
The ethanol-induced inhibition of facial stimulation-evoked outward currents was
dose-dependent, with an IC50 of 148.5 mM. Notably, the ethanol-induced inhibition
of facial stimulation-evoked outward currents were significantly abrogated by
cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1
agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial
stimulation-evoked outward currents was prevented by cerebellar surface perfusion
of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration
of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the
facial stimulation-evoked outward currents by activating presynaptic CB1
receptors via the PKA signaling pathway. These findings suggest that ethanol
overdose impairs sensory information processing, at least in part, by inhibiting
GABA release from molecular layer interneurons onto PCs.
PMID- 27489027
TI - Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry Method for
Profiling Ketolic and Phenolic Sex Steroids Using an Automated Injection Program
Combined with Diverter Valve Switch and Step Analysis.
AB - Sex steroids are involved in many physiological and pathological processes. The
determination of sex steroids is essential to understand the mechanisms of human
health and diseases. Derivatization techniques could specifically enhance the
sensitivities for sex steroids with a given functional group. However, no
derivatization reagents are available for profiling multifunctional sex steroids,
including phenolic estrogens, ketolic androgens, and ketolic progestogens, in a
single analytical run. In the present study, a novel method involving
ultraperformance liquid chromatography coupled with triple quadrupole mass
spectrometry (UPLC-MS/MS) was developed for profiling both ketolic and phenolic
sex steroids in human serum using an automated injection program combined with
diverter valve switch and step analysis (AIDSA). The human serum, prepared
through liquid-liquid extraction and subsequently derivatized using Girard P
offline, was automatically injected twice under the automated injection program.
For the first injection, Girard P-derivatized ketolic sex steroids were loaded
onto the column, and subsequently, the second injection and online derivatization
of the same sample using dansyl chloride were performed in the injector needle
for 15 min. The dansyl-labeled phenolic sex steroids were then loaded onto the
column. The diverter valve worked in coordination with the injection program to
import the derivatized sex steroids and remove excess derivatization reagents.
The two types of derivatives were individually analyzed in a step-by-step manner.
In addition, online dansyl derivatization and Girard P derivative analyses were
simultaneously implemented to shorten the total analysis time. This method was
well validated and applied to determine the sex steroid levels in human serum.
PMID- 27489028
TI - Real-World Data: Policy Issues Regarding their Access and Use.
AB - As real-world data (RWD) in health care begin to cross over to the Big Data
realms, a panel of health economists was gathered to establish how well the
current US policy environment further the goals of RWD and, if not, what can be
done to improve matters. This report summarizes these discussions spanning the
current US landscape of RWD availability and usefulness, private versus public
development of RWD assets, the current inherent bias in terms of access to RWD,
and guiding principles in providing quality assessments of new RWD studies. Three
main conclusions emerge: (1) a business case is often required to incentivize
investments in RWD assets. However, access restrictions for public data assets
have failed to generate a proper market for these data and hence may have led to
an underinvestment of public RWDs; (2) Very weak empirical evidence exist on for
profit entities misusing public RWD data entities to further their own agendas,
which is the basis for supporting access restrictions of public RWD data; and (3)
perhaps developing standardized metrics that could flag misuse of RWDs in an
efficient way could help quell some of the fear of sharing public RWD assets with
for-profit entities. It is hoped that these discussions and conclusions would
pave the way for more rigorous and timely debates on the greater availability and
accessibility of RWD assets.
PMID- 27489029
TI - Nucleation of Amyloid Oligomers by RepA-WH1-Prionoid-Functionalized Gold
Nanorods.
AB - Understanding protein amyloidogenesis is an important topic in protein science,
fueled by the role of amyloid aggregates, especially oligomers, in the etiology
of a number of devastating human degenerative diseases. However, the mechanisms
that determine the formation of amyloid oligomers remain elusive due to the high
complexity of the amyloidogenesis process. For instance, gold nanoparticles
promote or inhibit amyloid fibrillation. We have functionalized gold nanorods
with a metal-chelating group to selectively immobilize soluble RepA-WH1, a model
synthetic bacterial prionoid, using a hexa-histidine tag (H6). H6-RepA-WH1
undergoes stable amyloid oligomerization in the presence of catalytic
concentrations of anisotropic nanoparticles. Then, in a physically separated
event, such oligomers promote the growth of amyloid fibers of untagged RepA-WH1.
SERS spectral changes of H6-RepA-WH1 on spherical citrate-AuNP substrates provide
evidence for structural modifications in the protein, which are compatible with a
gradual increase in beta-sheet structure, as expected in amyloid oligomerization.
PMID- 27489031
TI - Small molecule based N-phenyl carbazole substituted diketopyrrolopyrroles as
donors for solution-processed bulk heterojunction organic solar cells.
AB - We report two acetylene-bridged small molecules DPP5 and DPP6 with low HOMO-LUMO
gaps as donors along with PC71BM as an acceptor for the fabrication of solution
processed bulk heterojunction solar cells. After the optimization, i.e. weight
ratio of donor to acceptor and surface treatment of the active layer, we achieved
overall power conversion efficiencies up to 4.65% (Jsc = 8.19 mA cm(-2), Voc =
0.98 V and FF = 0.58) and 5.73% (Jsc = 9.58 mA cm(-2), Voc = 0.98 V and FF =
0.61), for DPP5:PC71BM and DPP6:PC71BM respectively, which are superior to those
for the devices based on as-cast active layers. The significant change in the
power conversion efficiency is attributed to the improvement in nanoscale
morphology, balanced charge transport and charge collection efficiency, induced
through the surface treatment.
PMID- 27489030
TI - Isothiourea-catalysed enantioselective pyrrolizine synthesis: synthetic and
computational studies.
AB - The catalytic enantioselective synthesis of a range of cis-pyrrolizine
carboxylate derivatives with outstanding stereocontrol (14 examples, >95 : 5 dr,
>98 : 2 er) through an isothiourea-catalyzed intramolecular Michael addition
lactonisation and ring-opening approach from the corresponding enone acid is
reported. An optimised and straightforward three-step synthetic route to the
enone acid starting materials from readily available pyrrole-2-carboxaldehydes is
delineated, with benzotetramisole (5 mol%) proving the optimal catalyst for the
enantioselective process. Ring-opening of the pyrrolizine dihydropyranone
products with either MeOH or a range of amines leads to the desired products in
excellent yield and enantioselectivity. Computation has been used to probe the
factors leading to high stereocontrol, with the formation of the observed cis
steroisomer predicted to be kinetically and thermodynamically favoured.
PMID- 27489032
TI - Facial Soft Tissue Depth Measurement: Validation of the 75-Shormax.
AB - The shorth and 75-shormax were recently posited as an improved alternative to the
arithmetic mean for describing facial soft tissue thicknesses in craniofacial
identification. The shorth better estimates the data peak, while the 75-shormax
provides improved provisions for a long right tail. When first proposed, the 75
shormax was subjectively gauged. Herein, shormax errors are calculated at every
whole percentile to quantitatively determine zones of error minimization in two
large samples: (a) CT data of French adults, n-range = 211-469 individuals; and
(b) all C-Table data, n-range = 60-1065 individuals [including part but not all
of sample (a)]. The smallest residuals were found at the 79th percentile (mean of
raw residuals) and the 74th percentile (mean of absolute residuals). The 75
shormax is subsequently verified as good error minimizer since the absolute
differences carry the greatest weight and the 74th percentile closely
approximates the 75th percentile.
PMID- 27489033
TI - The association of three promoter polymorphisms in interleukin-10 gene with the
risk for colorectal cancer and hepatocellular carcinoma: A meta-analysis.
AB - Mounting evidence supports a potent inhibitory role of interleukin-10 (IL-10) in
tumor carcinogenesis, angiogenesis and metastasis. This meta-analysis was
designed to examine the association of three promoter polymorphisms (-592C > A,
819C > T and -1082G > A) in IL-10 gene with the risk for colorectal cancer and
hepatocellular carcinoma. Qualification assessment and data collection were
completed by two authors independently. The random-effects model using the
DerSimonian and Laird method was fitted by the STATA software. Twenty-five
articles involving 5933 cases and 9724 controls were meta-analyzed. Overall
comparisons of the mutant alleles (-592A, -819T and -1082A) of three promoter
polymorphisms with alternative wild alleles failed to reveal any statistical
significance for both colorectal cancer and hepatocellular carcinoma (P > 0.05),
and the likelihood of heterogeneity was low (I(2) < 50%). For -592C > A
polymorphism, a significant risk for colorectal cancer was identified when
analysis was restricted to East Asians (odds ratio or OR = 1.41, 95% confidence
interval or CI: 1.18-1.68, P < 0.001) and retrospective studies (OR = 1.23, 95%
CI: 1.09-1.39, P = 0.001). As weighed by the Egger's test and the fill-and-trim
method, there was a low probability of publication bias for all studied
polymorphisms. Our findings collectively suggest that the -592C > A polymorphism
in IL-10 gene might be a susceptibility locus for colorectal cancer in East
Asians.
PMID- 27489035
TI - Correction to Drag Reduction using Lubricant-Impregnated Surfaces in Viscous
Laminar Flow.
PMID- 27489034
TI - The impact of lower limb chronic oedema on patients' quality of life.
AB - This study aimed to explore patients' perceptions regarding the impact that lower
limb chronic oedema has on their quality of life (QoL). A quantitative
descriptive design was used to collect data from patients with lower limb chronic
oedema. A condition-specific validated questionnaire was distributed to a
purposive sample (n = 122) through manual lymphatic drainage/vascular/health
clinics in Ireland. Results indicated that patients with lower limb chronic
oedema experience a wide range of physical problems such as limb heaviness (74%,
n = 66), weakness (44%, n = 40) and pain (38%, n = 34). Additionally,
difficulties with walking (53%, n = 48), standing (51%, n = 46) and bending (45%,
n = 40) were reported. Concerns regarding poor body image were strongly evident
(76%, n = 68). Difficulties finding clothing/footwear to fit oedematous limb(s)
were reported (59%, n = 53), in addition to finding clothes that participants
would like to wear (64%, n = 58). Emotional symptoms of irritability (42%, n =
38), anxiety (41%, n = 37) and tension (40%, n = 36) were reported. Over half of
the participants (55%, n = 49) stated that their chronic swelling affected their
social functioning and their ability to engage in leisure activities. This study
has identified that lower limb chronic oedema has significant psychological,
social and physical implications for persons' QoL.
PMID- 27489036
TI - Medication use and adherence among multi-ethnic community-dwelling older adults
in Malaysia.
AB - AIM: The present study assessed adherence, barriers, belief and awareness towards
the use of medications among multi-ethnic community-dwelling older adults in
Malaysia. Medication accessibility, expenditure and perceptions towards medicine
labeling among older adults were also evaluated. METHODS: A cross-sectional study
was carried out in the central region of Malaysia from January to August 2015.
The older adults enrolled in an ongoing prospective community-based geriatric
cohort study and prescribed with medicines were interviewed using a 50-item
validated questionnaire. RESULTS: Of the 79 older adults interviewed, 39.2% had
>=4 prescribed medications. Most obtained their medications free-of-charge from
government hospitals (66, 83.5%). Nearly half (35, 44.3%) had trouble reading
labels for medicines that they had received. Chinese older adults (P = 0.001) and
those with lower monthly household income (P < 0.001) expressed difficulty in
reading medication labels. Most (59, 75.0%) were unable to differentiate between
generic and brand names of the medications, and 49.4% of the older adults did not
know that all medicines had to be registered with the Ministry of Health,
Malaysia. Most older adults had positive beliefs about the necessity of their
medications, and 50.6% (n = 40) reported high medication adherence. The
medication adherence score was negatively correlated with the concerns score (r =
-0.5, P < 0.001). CONCLUSIONS: The findings from the present study provide a
unique insight into the diversity of medication use among multiethnic community
dwelling older adults. Although high adherence to medications and positive
beliefs about the necessity of medications were reported by the older adults,
their knowledge about medications remained insufficient and they had difficulty
in reading medication labels. Geriatr Gerontol Int 2017; 17: 1214-1220.
PMID- 27489037
TI - Evidence of proteinuria, but no other characteristics of pre-eclampsia, in
relaxin-deficient mice.
AB - Pre-eclampsia (PE) is a leading cause of maternal and fetal death, characterised
by an imbalance of placental growth factors and hypertension at >20 weeks
gestation. Impaired maternal systemic vascular adaptations and fetal growth
restriction are features of both PE and pregnant relaxin-deficient (Rln-/-) mice.
The aim of the present study was to investigate whether these phenotypes in Rln-/
mice are associated with abnormal placental growth factor expression, increased
soluble fms-like tyrosine kinase-1 (sFlt-1), proteinuria and/or hypertension
during pregnancy. In addition, we examined relaxin and relaxin receptor
(relaxin/insulin like family peptide receptor 1 (RXFP1)) mRNA expression in
placentas of women with PE. There was no significant difference in placental
vascular endothelial growth factor A (VegfA) and placenta growth factor (Plgf)
gene expression between Rln-/- and wild-type mice. Circulating plasma sFlt-1
concentrations in pregnant mice of both genotypes and ages were increased
compared with non-pregnant mice but were lower in younger pregnant Rln-/- mice
compared with aged-matched Rln+/+ mice. Aged pregnant Rln-/- mice had higher
urinary albumin:creatinine ratios compared with age-matched Rln+/+ mice,
indicative of proteinuria. Systolic and diastolic blood pressures did not differ
between genotypes. In addition, PE in women was not associated with altered
placental mRNA expression of RLN2 or RXFP1 at term. Overall, the data demonstrate
that pregnant Rln-/- mice do not have the typical characteristics of PE. However,
these mice show evidence of proteinuria, but we suggest that this results from
systemic renal vascular dysfunction before pregnancy.
PMID- 27489039
TI - An all-atom, active site exploration of antiviral drugs that target Flaviviridae
polymerases.
AB - Natural 2'-modified nucleosides are the most widely used antiviral therapy. In
their triphosphorylated form, also known as nucleotide analogues, they target the
active site of viral polymerases. Viral polymerases have an overall right-handed
structure that includes the palm, fingers and thumb domains. These domains are
further subdivided into structurally conserved motifs A-G, common to all viral
polymerases. The structural motifs encapsulate the allosteric/initiation (N1) and
orthosteric/catalytic (N2) nucleotide-binding sites. The current study
investigated how nucleotide analogues explore the N2 site of viral polymerases
from three genera of the family Flaviviridae using a stochastic, biophysical,
Metropolis Monte Carlo-based software. The biophysical simulations showed a
statistical distinction in nucleotide-binding energy and exploration between
phylogenetically related viral polymerases. This distinction is clearly
demonstrated by the respective analogue contacts made with conserved viral
polymerase residues, the heterogeneous dynamics of structural motifs, and the
orientation of the nucleotide analogues within the N2 site. Being able to
simulate what occurs within viral-polymerase-binding sites can prove useful in
rational drug designs against viruses.
PMID- 27489040
TI - Chromatin silencing maintains the identity of intestinal stem cells.
PMID- 27489041
TI - One step engineering of the small-subunit ribosomal RNA using CRISPR/Cas9.
AB - Bacteria are indispensable for the study of fundamental molecular biology
processes due to their relatively simple gene and genome architecture. The
ability to engineer bacterial chromosomes is quintessential for understanding
gene functions. Here we demonstrate the engineering of the small-ribosomal
subunit (16S) RNA of Mycoplasma mycoides, by combining the CRISPR/Cas9 system and
the yeast recombination machinery. We cloned the entire genome of M. mycoides in
yeast and used constitutively expressed Cas9 together with in vitro transcribed
guide-RNAs to introduce engineered 16S rRNA genes. By testing the function of the
engineered 16S rRNA genes through genome transplantation, we observed surprising
resilience of this gene to addition of genetic elements or helix substitutions
with phylogenetically-distant bacteria. While this system could be further used
to study the function of the 16S rRNA, one could envision the "simple" M.
mycoides genome being used in this setting to study other genetic structures and
functions to answer fundamental questions of life.
PMID- 27489042
TI - Shh... Sweat gland in progress!
PMID- 27489043
TI - On the potential for BECCS efficiency improvement through heat recovery from both
post-combustion and oxy-combustion facilities.
AB - In order to mitigate climate change to no more than 2 degrees C, it is well
understood that it will be necessary to directly remove significant quantities of
CO2, with bioenergy CCS (BECCS) regarded as a promising technology. However,
BECCS will likely be more costly and less efficient at power generation than
conventional CCS. Thus, approaches to improve BECCS performance and reduce costs
are of importance to facilitate the deployment of this key technology. In this
study, the impact of biomass co-firing rate and biomass moisture content on BECCS
efficiency with both post- and oxy-combustion CO2 capture technologies was
evaluated. It was found that post-combustion capture BECCS (PCC-BECCS) facilities
will be appreciably less efficient than oxy-combustion capture BECCS (OCC-BECCS)
facilities. Consequently, PCC-BECCS have the potential to be more carbon negative
than OCC-BECCS per unit electricity generated. It was further observed that the
biomass moisture content plays an important role in determining the BECCS
facilities' efficiency. This will in turn affect the enthalpic content of the
BECCS plant exhaust and implies that exhaust gas heat recovery may be an
attractive option at higher rates of co-firing. It was found that there is the
potential for the recovery of approximately 2.5 GJheat per tCO2 at a temperature
of 100 degrees C from both PCC-BECCS and OCC-BECCS. On- and off-site
applications for this recovered heat are discussed, considering boiler feedwater
pre-heating, solvent regeneration and district heating cases.
PMID- 27489044
TI - Polarization-dependent fluorescence correlation spectroscopy for studying
structural properties of proteins in living cell.
AB - Rotational diffusion measurement is predicted as an important method in cell
biology because the rotational properties directly reflect molecular interactions
and environment in the cell. To prove this concept, polarization-dependent
fluorescence correlation spectroscopy (pol-FCS) measurements of purified
fluorescent proteins were conducted in viscous solution. With the comparison
between the translational and rotational diffusion coefficients obtained from pol
FCS measurements, the hydrodynamic radius of an enhanced green fluorescent
protein (EGFP) was estimated as a control measurement. The orientation of
oligomer EGFP in living cells was also estimated by pol-FCS and compared with
Monte Carlo simulations. The results of this pol-FCS experiment indicate that
this method allows an estimation of the molecular orientation using the
characteristics of rotational diffusion. Further, it can be applied to analyze
the degree of molecular orientation and multimerization or detection of tiny
aggregation of aggregate-prone proteins.
PMID- 27489045
TI - Cytotoxic Oxygenated Steroids from the Soft Coral Nephthea erecta.
AB - A new 10-demethylated steroid, nephtheasteroid A (1), a new 19-oxygenated
steroid, nephtheasteroid B (2) as well as five known steroids 3-7 were isolated
from the organic extract of a Taiwanese soft coral Nephthea erecta. The structure
was determined by means of IR, MS, and NMR techniques. Among these metabolites, 1
is rarely found in steroids possessing a 19-norergostane skeleton. In vitro
cytotoxicity study using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay revealed that compounds 3 and 4 exhibited cytotoxicity
against human chronic myelogenous leukemia (K562), human acute lymphoblastic
leukemia (Molt-4), human T lymphoblastoid (Sup-T1), and human leukemic monocyte
lymphoma (U937), with IC50 of 6.5-14.0 uM.
PMID- 27489046
TI - Practical Synthesis of Axially Chiral Dicarboxylates via Pd-Catalyzed External-CO
Free Carbonylation.
AB - We have developed a safe and practical synthetic method for preparing axially
chiral diphenyl dicarboxylates using Pd-catalyzed external-CO-free carbonylation
with phenyl formate as a CO surrogate. Optimized conditions consisted of axially
chiral [1,1'-binaphthalene]-2,2'-diyl ditriflate and its congeners, each easily
prepared from commercially available enantiomerically pure diols, Pd(OAc)2, 1,3
bis(diphenylphosphino)propane, ethyldiisopropylamine, and no solvent. To
demonstrate the potential utility of these products, this method was conducted on
gram-scale and the phenyl ester products were converted to other useful
compounds, and both processes were carried out without difficulty.
PMID- 27489047
TI - Papilloedema secondary to oligodendroglioma.
AB - Oligodendrogliomas are rare slow-growing asymptomatic glial tumours that usually
present in patients in their fourth to sixth decades of life. Neurological
symptoms that may present include nausea, headache, vomiting, diplopia,
confusion, focal weakness, numbness and seizures. The treatment of
oligodendroglioma tumours is based on functional status classification, lumbar
puncture, imaging of the head, tumour biopsy and genetic testing. Grades II and
IV oligodendroglial tumours, which have co-deletion of the short arm of
chromosome 1 (1p) and the long arm of chromosome 19 (19q) and mutations in
isocitrate dehydrogenase, have the most favourable prognosis, as they respond
well to neurosurgery and chemotherapy. This report will discuss a general case of
papilloedema in a young patient with oligodendroglioma and the role of the
optometrist in its post-neurosurgical and chemotherapeutic care.
PMID- 27489049
TI - Efficacy and safety of doublet versus single agent as salvage treatment for
metastatic breast cancer pretreated with anthracyclines and taxanes: a systematic
review and meta-analysis.
AB - AIM: To perform a systematic review and meta-analysis of randomized controlled
trials to compare the efficacy and safety of doublet versus single agent as
salvage treatment for pretreated metastatic breast cancer. METHODS: A
comprehensive literature search was performed to identify relevant randomized
controlled trials (RCTs). All clinical studies were independently identified by
two authors for inclusion. Demographic data, treatment regimens, objective
response rate (ORR), and progression-free survival (PFS) and overall survival
(OS) were extracted and analyzed using Comprehensive MetaAnalysis software
(Version 2.0). RESULTS: Thirteen RCTs involving 4878 pretreated metastatic breast
cancer patients were ultimately identified. The pooled results demonstrated that
doublet combination therapy significantly improved ORR (RR 1.13, 95% CI: 1.01
1.27, p < .001) and PFS (hazard ration [HR] 0.83, 95% CI: 0.73-0.96, p = .011),
but not OS (HR 0.93, 95% CI: 0.86-1.01, p = .065). Similar results were observed
in sub-group analysis according to treatment regimens. Additionally, more
incidences of grade 3 or 4 myelosuppression toxicities nausea and fatigue were
observed in doublet combination therapy. CONCLUSIONS: In comparison with a single
agent alone, doublet combination therapy as salvage treatment for pretreated
metastatic breast cancer patients significantly improves ORR and PFS, but not OS.
Further studies are recommended to identify patients who will most likely benefit
from the appropriate doublet combination therapy.
PMID- 27489050
TI - Eccentric Atrial Activation During a Narrow QRS Tachycardia: What Is the
Mechanism?
PMID- 27489048
TI - DNA hydroxymethylation controls cardiomyocyte gene expression in development and
hypertrophy.
AB - Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification
associated recently with cardiac disease. In contrast, the role of 5
hydroxymethylcytosine (5-hmC)-5-mC's oxidation product-in cardiac biology and
disease is unknown. Here we assess the hydroxymethylome in embryonic, neonatal,
adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of
hydroxymethylated DNA is associated with specific transcriptional networks during
heart development and failure. DNA hydroxymethylation marks the body of highly
expressed genes as well as distal regulatory regions with enhanced activity.
Moreover, pathological hypertrophy is characterized by a shift towards a neonatal
5-hmC distribution pattern. We also show that the ten-eleven translocation 2
(TET2) enzyme regulates the expression of key cardiac genes, such as Myh7,
through 5-hmC deposition on the gene body and at enhancers. Thus, we provide a
genome-wide analysis of 5-hmC in the cardiomyocyte and suggest a role for this
epigenetic modification in heart development and disease.
PMID- 27489051
TI - Myocarditis in Clinical Practice.
AB - Myocarditis is a polymorphic disease characterized by great variability in
clinical presentation and evolution. Patients presenting with severe left
ventricular dysfunction and life-threatening arrhythmias represent a demanding
challenge for the clinician. Modern techniques of cardiovascular imaging and the
exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have
provided valuable insight into the pathophysiology of this disease, and several
clinical registries have unraveled the disease's long-term evolution and
prognosis. However, uncertainties persist in crucial practical issues in the
management of patients. This article critically reviews current information for
evidence-based management, offering a rational and practical approach to patients
with myocarditis. For this review, we searched the PubMed and MEDLINE databases
for articles published from January 1, 1980, through December 31, 2015, using the
following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial
biopsy. Articles were selected for inclusion if they represented primary data or
were review articles published in high-impact journals. In particular, a risk
oriented approach is proposed. The different patterns of presentation of
myocarditis are classified as low-, intermediate-, and high-risk syndromes
according to the most recent evidence on prognosis, clinical findings, and both
invasive and noninvasive testing, and appropriate management strategies are
proposed for each risk class.
PMID- 27489052
TI - Postoperative Pyoderma Gangrenosum: A Clinical Review of Published Cases.
AB - Postoperative pyoderma gangrenosum (PG) is a neutrophilic dermatosis
characterized by PG at surgical incisions. It is often misdiagnosed as wound
infection, and pathergy may complicate wound debridement. From September 1, 2013,
through November 30, 2013, a literature search was conducted of articles
published from January 1, 1978, through December 31, 2012. We referenced PubMed,
MEDLINE, and Mayo Clinic Libraries using the keywords pyoderma gangrenosum,
postoperative pyoderma gangrenosum, postsurgical pyoderma gangrenosum,
superficial granulomatous pyoderma, pathergic pyoderma, and pyoderma gangrenosum
associated with surgery, incision, breast, and wound dehiscence. In addition, all
titles from PubMed with the words pyoderma gangrenosum were reviewed manually for
postoperative cases. Of 136 patients, 90 (66%) did not have associated systemic
diseases. If a comorbidity was present, hematologic disorders were most common.
In addition, 29% (28) of women had predisposing disease vs 53% (19) of men. Women
had more frequent breast involvement (P<.001); chest involvement was more common
in men (P=.005). Girls and women aged 13 to 64 years had more frequent breast
involvement (P=.01). Sites were distributed equally for men regardless of age
(P=.40). Antibiotic drug therapy was begun and debridement occurred in 90% (110
of 122 treated patients) and 73% (90 of 123 available patients), respectively.
Postoperative PG has less association with systemic disease than its
nonpostoperative counterpart. Antibiotic drug therapy is routinely initiated.
Affected sites are often debrided, causing additional wound breakdown. Early
diagnosis may prevent complications.
PMID- 27489053
TI - Secondary preventive medication use in a prevalent population-based cohort of
acute coronary syndrome survivors.
AB - AIM: Describe the dispensing patterns for guideline-recommended medications
during 2008 in people with acute coronary syndrome (ACS) and how dispensing
varies by gender and time since last ACS hospitalization. METHOD: A descriptive
cohort spanning 20 years of people alive post-ACS in 2008. We extracted all ACS
hospitalizations and deaths in Western Australia (1989-2008), and all person
linked Pharmaceutical Benefits Scheme claims nationally for 2008. Participants
were 23 642 men and women (36.8%), alive and aged 65-89 years in mid-2008 who
were hospitalized for ACS between 1989 and 2008. Main outcome was the proportion
of the study cohort (in 2008) dispensed guideline-recommended cardiovascular
medications in that year. Adjusted odds ratios estimating the association between
type (and number) of guideline-recommended medications and time since last ACS
hospitalization. RESULTS: Medications most commonly dispensed in 2008 were
statins (79.6% of study cohort) and then angiotensin-converting enzyme inhibitors
or angiotensin-receptor blockers (ACEi/ARBs) (71.1%), aspirin or clopidogrel
(59.4%), and beta-blockers (54.6%). Only 51.8% of the cohort was dispensed three
or more of these drug types in 2008. Women with ACS were 18% less likely to be
dispensed statins (adjusted odds ratio (OR)=0.82; 95% CI 0.76-0.88). Overall, for
each incremental year since last ACS admission, there was an 8% increased odds
(adjusted OR=1.08; 95% CI 1.07-1.08) of being dispensed fewer of the recommended
drug regimen in 2008. CONCLUSION: Longer time since last ACS admission was
associated with dispensing fewer medications types and combinations in 2008.
Interventions are warranted to improve dispensing long term and any apparent
gender inequality in the drug class filled.
PMID- 27489055
TI - Metabolomic study of wild and cultivated caper (Capparis spinosa L.) from
different areas of Sardinia and their comparative evaluation.
AB - Capparis spinosa L. (Capparidaceae), also known as caper, is widely known for its
very aromatic flower buds (capers),that are largely employed as a flavouring in
cooking. Capparis species are regarded as a potential source of important
bioactive compounds, in fact, due to their botanical relationship with Brassica
species; they contain glucosinolates, secondary plant metabolites, that have been
studied for their potential anticarcinogenic properties. In addition, the
presence of other numerous beneficial compounds such as polyphenols, alkaloids,
lipids, vitamins and minerals have been reported. The aim of this study was to
individuate and determinate the principal bioactive compounds occurring in
different part (leaves, buds and flowers) of wild and cultivated C. spinosa
collected from different area of Sardinia (Italy). Ultra-high performance liquid
chromatography-triple quadrupole/linear ion trap tandem mass spectrometry methods
were used for identification and simultaneous determination of 27 bioactive
molecules. Analysis of different samples revealed qualitative and quantitative
differences in the content of flavonoids, glucosinolates, anthocyanins and
phenolic acids. In particular, glucocapparin resulted the most abundant with
values ranging from 112 to 364 mg/100 g Fresh Weight (FW); followed by rutin with
highest value of 126 mg/100 g FW, 4-hydroxyglucobrassicin with highest value of
42 mg/100 g FW and isorhamnetin 3-O-rutinoside with highest value of 24 mg/100 g
FW. Based on this metabolomic targeted approach, quantitative results were
treated by principal component analysis to explore and visualise correlation and
discrimination among collections of C. spinosa samples. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27489054
TI - Load-induced enhancement of Dynein force production by LIS1-NudE in vivo and in
vitro.
AB - Most sub-cellular cargos are transported along microtubules by kinesin and dynein
molecular motors, but how transport is regulated is not well understood. It is
unknown whether local control is possible, for example, by changes in specific
cargo-associated motor behaviour to react to impediments. Here we discover that
microtubule-associated lipid droplets (LDs) in COS1 cells respond to an optical
trap with a remarkable enhancement in sustained force production. This effect is
observed only for microtubule minus-end-moving LDs. It is specifically blocked by
RNAi for the cytoplasmic dynein regulators LIS1 and NudE/L (Nde1/Ndel1), but not
for the dynactin p150(Glued) subunit. It can be completely replicated using cell
free preparations of purified LDs, where duration of LD force production is more
than doubled. These results identify a novel, intrinsic, cargo-associated
mechanism for dynein-mediated force adaptation, which should markedly improve the
ability of motor-driven cargoes to overcome subcellular obstacles.
PMID- 27489056
TI - Preoperative Paravertebral Block Improves Postoperative Pain Control and Reduces
Hospital Length of Stay in Patients Undergoing Autologous Breast Reconstruction
after Mastectomy for Breast Cancer.
AB - BACKGROUND: Postoperative pain is a major challenge for patients undergoing
breast reconstruction after surgical treatment of breast cancer, resulting in
prolonged hospitalizations and additional resource utilization. Evidence on the
efficacy of techniques to minimize postoperative pain in autologous breast
reconstruction is lacking. We sought to determine whether preoperative
paravertebral block (PVB), a regional anesthetic technique, affects postoperative
pain control and hospital length of stay (LOS) in patients undergoing autologous
breast reconstruction. METHODS: Consecutive patients undergoing postmastectomy
autologous breast reconstruction between 2012 and 2015 were identified from a
prospectively collected database to compare those who received PVB to those who
did not. Primary outcomes included self-reported pain score, time to oral-only
narcotic usage (TTON), and LOS. Sample differences were compared using Wilcoxon
rank-sum and Chi square tests for continuous and categorical variables. Kaplan
Meier analysis was used to evaluate TTON and LOS, with Mantel-Cox test used to
compare groups. RESULTS: Of 78 patients, 39 received PVB and 39 did not. Study
groups did not differ regarding age, body mass index, American Society of
Anesthesiologists class, mastectomy type, flap type, or cancer stage (p > 0.05).
Patients in the PVB group reported significantly lower postoperative pain at 2 (p
< 0.01) and 24 h (p < 0.01) and shorter median TTON (66 vs. 76 h, p < 0.01).
Importantly, median LOS was reduced for patients receiving a PVB in both hours
(95 vs. 116, p < 0.01) and hospital nights (4 vs. 5, p = 0.05). CONCLUSIONS:
Preoperative PVB is associated with improved postoperative pain control and
shorter hospitalizations for patients with breast cancer undergoing
postmastectomy autologous reconstruction.
PMID- 27489057
TI - Short- and Long-Term Outcomes After Gastrectomy in Elderly Gastric Cancer
Patients.
AB - BACKGROUND: The number of elderly patients undergoing gastric cancer surgery has
recently increased. We therefore evaluated the short- and long-term outcomes of
elderly patients after curative gastrectomy. METHODS: Overall, 824 patients were
included in this retrospective study, which comprised of a non-elderly group (60
64 years; n = 558), an early-elderly group (75-79 years; n = 198), and a late
elderly group (>=80 years; n = 68) who underwent curative gastrectomy for gastric
cancer between 2005 and 2009. Postoperative complications, according to the
Clavien-Dindo classification, and survival of both elderly groups were compared
with the non-elderly group. Postoperative life expectancy of the late-elderly
group was compared with the corresponding aged general population. RESULTS:
Overall and severe (grade III or higher) complications in the early-elderly group
were comparable with the non-elderly group; however, those in the late-elderly
group were significantly more common than in the non-elderly group (p = 0.013 and
p = 0.043, respectively). Multivariable analysis revealed that age >=80 years was
an independent risk factor for severe complications (hazard ratio 3.02, 95 %
confidence interval 1.12-8.17; p = 0.029), and the disease-specific survivals of
both elderly groups were comparable with the non-elderly group in all TNM stages.
Postoperative life expectancy of late-elderly patients eliminating death from
recurrence was comparable with the corresponding aged general population
eliminating death from gastric cancer. CONCLUSIONS: Gastric cancer surgery in
elderly patients aged >=80 years achieves reasonable long-term survival despite
the increased risk of severe complications.
PMID- 27489058
TI - Minimally Invasive Gastric Surgery.
AB - The incidence of gastric cancer is increasing in the United States, particularly
for various subtypes as well as presenting in earlier states. Such changes have
allowed various centers to increasingly offer less invasive approaches to the
treatment of gastric cancer, namely laparoscopic and robotic techniques.
Minimally invasive gastrectomy has been suggested to have similar oncology
outcomes compared to open procedures. In the last two decades, large
retrospective and a series of randomized trials evaluated the role of minimally
invasive gastrectomy for early gastric cancer, distal gastrectomy, total
gastrectomy and advanced gastric cancer. As the experience with emerging
technologies such as robotic assisted gastrectomies increases, the indications
for minimally invasive surgery will likely expand.
PMID- 27489060
TI - Narrow QRS Tachycardia with Long RP Interval: What Is the Mechanism?
PMID- 27489059
TI - Long-Term Outcome of Rectal Cancer With Clinically (EUS/MRI) Metastatic
Mesorectal Lymph Nodes Treated by Neoadjuvant Chemoradiation: Role of Organ
Preservation Strategies in Relation to Pathologic Response.
AB - BACKGROUND: Organ preservation strategies are under investigation for patients
with locally advanced rectal cancer (LARC) who achieve a complete pathologic
response in the primary tumor (ypT0) after neoadjuvant chemoradiation therapy
(CRT). This study explored the value of this approach for cN+ patients. METHODS:
Data were retrieved from our institutional prospective rectal cancer database.
Tumors with mesorectal lymph nodes larger than 5 mm shown on endorectal
ultrasonography, pelvic magnetic resonance imaging, or both were staged as cN+.
RESULTS: The study population comprised 226 patients (142 men and 84 women;
median age, 64 years) with LARC who underwent CRT followed by surgery including
total mesorectal excision (TME) (n = 179) and full-thickness local excision (LE)
(n = 47) between 1996 and 2013. At staging, 123 patients (54.4 %) were cN+. In 65
cases (28.7 %), ypCR was observed. Metastatic mesorectal lymph nodes (ypN+) were
detected in 41.6 % of the cN+ patients and in 2.8 % of the cN0 patients (P <
0.01). Among the cN+ patients, 16 % of the ypT0 cases were ypN+ compared with
51.8 % of the no-ypT0 cases (P < 0.01). Among the cN+ patients who underwent TME,
the 5-year disease-specific survival (DSS) and disease-free survival (DFS) rates
were respectively 100 and 91.6 % for the ypT0 patients compared with 71.2 and
58.0 % for the no-ypT0 patients (P = 0.01). Among the ypN+ patients, the 5-year
DSS and DFS rates were both 100 % for the ypT0 cases compared with 59.1 and 43.3
% for the no-ypT0 patients. Among the cN+ and ypT0 patients, the 5-year DSS and
DFS were respectively 100 and 85.7 % for the TME patients compared with 100 and
91.6 % for the LE patients. In the multivariate analysis, ypT0 was the only
independent prognostic factor. CONCLUSIONS: Protocols aimed at organ preservation
in LARC that achieve ypT0 after CRT can be offered also to cN+ patients.
PMID- 27489061
TI - Posterior reversible encephalopathy syndrome (PRES) as a complication of Guillain
Barre' syndrome (GBS).
AB - A 17-year-old Pakistani female patient presented with acute onset flaccid
quadriparesis with nerve conduction studies showing demyelinating polyneuropathy
consistent with Guillain-Barre' syndrome. She was treated with 4 plasmapheresis
sessions. She developed raised blood pressure, headache, visual loss and
generalised seizures on the 13th day of admission. MRI of the brain on contrast
showed findings of altered signals low on T1-weighted image, high on T2-weighted
image and fluid-attenuated inversion recovery in the white matter of bilateral
occipital, parietal and right frontal lobe consistent with posterior reversible
encephalopathy syndrome. The patient was administered antiepileptic and
antihypertensive drugs to control seizures and blood pressure. She was discharged
in a stable state. On follow-up her visual loss had recovered completely and she
had regained full motor strength in all four extremities after 6 weeks. Fresh MRI
of the brain revealed complete resolution of lesions. Antihypertensive and
antiepileptic medication was discontinued. She is independent in all her daily
activities.
PMID- 27489062
TI - Tamoxifen precipitation of familial hypertriglyceridaemia: a rare cause of acute
pancreatitis.
AB - Drug-induced pancreatitis is uncommon, and is estimated to account for between
0.1% and 5% of cases. Tamoxifen is commonly used in the management of oestrogen
receptor-positive breast cancer. We present a rare case of tamoxifen-related
hyperlipidaemia resulting in repeated episodes of pancreatitis, which, to the
best of our knowledge, has only been documented a few times in the literature. A
36-year-old woman with familial hypertriglyceridaemia presented with recurrent
episodes of abdominal pain, modest increases in serum amylase levels and normal
liver function tests. The patient had recently been diagnosed with breast
carcinoma and was managed with wide local excision (WLE), adjuvant radiotherapy
and tamoxifen. On each admission, the patient's symptoms were confirmed either
biochemically and/or radiologically. Analysis of the case led to a diagnosis of
precipitation of familial hypertriglyceridaemia from tamoxifen use resulting in
pancreatitis. Management was altered with tamoxifen cessation and initiation of
second-line hormonal therapy. Tamoxifen use needs consideration, especially in
those with familial hyperlipidaemia.
PMID- 27489063
TI - Non-lethal Clostridium sordellii bacteraemia in an immunocompromised patient with
pleomorphic sarcoma.
AB - Clostridium sordellii is a spore-forming anaerobic Gram-positive rod that has
rarely been reported to cause disease in humans. Resultant mortality from
infection is estimated at nearly 70% and is most often correlated with
gynaecological procedures, intravenous drug abuse or trauma. C. sordellii
infection often presents similarly to toxic shock syndrome (TSS); notable
features of infection include refractory hypotension, haemoconcentration and
marked leucocytosis. Although clinically similar to TSS, a notable difference is
C. sordellii infections rarely involve fever. The organism's major toxins include
haemorrhagic (TcsH) and lethal factor (TcsL), which function to disrupt
cytoskeletal integrity. Current literature suggests treating C. sordelli
infection with a broad-spectrum penicillin, metronidazole and clindamycin. We
present a case of C. sordellii bacteraemia and septic shock in an
immunocompromised patient who was recently diagnosed with pleomorphic gluteal
sarcoma. Despite presenting in critical condition, the patient improved after
aggressive hemodynamic resuscitation, source control and intravenous antibiotic
therapy.
PMID- 27489064
TI - Silent myocardial infarction secondary to cardiac autonomic neuropathy in a
patient with rheumatoid arthritis.
AB - An 83-year-old female patient with rheumatoid arthritis and hypertension
presented to the emergency department with fever and chills of 1 day duration. On
examination, temperature was 100.9 F, heart rate 111/min and she had orthostatic
hypotension. Laboratory tests showed elevated blood urea nitrogen and white cell
count. The patient underwent treatment for symptomatic urinary tract infection
and while her fever and leucocytosis resolved, tachycardia persisted. An EKG done
showed T inversions in leads II, III, arteriovenous fistula, V2 and V3. Troponin
I was elevated. Nuclear stress test revealed apical wall motion abnormality
confirming myocardial infarction. Ewing's tests were carried out at bedside and
these diagnosed severe autonomic neuropathy. Rheumatoid arthritis can cause
cardiac autonomic neuropathy from chronic inflammation. This case entails the
importance of assessing and detecting cardiac autonomic neuropathy in chronic
inflammatory conditions, and the need to be cautious of acute coronary events in
these patients, even for minimal or no symptoms.
PMID- 27489065
TI - Urgent decisions and a tight spot: embolic infarction of a herniated cerebellar
tonsil.
AB - A previously well 30-year-old woman presented at 17:30 with a sudden onset of
dizziness, ataxia and headache. She was initially investigated with a CT scan of
the brain and lumbar puncture, which yielded no diagnosis. Subsequent MR scan
revealed multiple posterior circulation infarcts, along with a previously
undiagnosed Arnold-Chiari 2 malformation with an associated syrinx of her
cervical and thoracic spine. The infarct involved one of the herniated cerebellar
tonsils. Oedema of an infarct in the herniated tonsils caused compression of the
medulla at the foramen magnum, with associated neurological symptoms including
Lhermitte's phenomenon and headache on valsalva manoeuvre. Owing to these
symptoms a surgical decompression was performed. The most likely aetiology of her
stroke was determined to be a paradoxical embolus via patent foramen ovale.
PMID- 27489066
TI - Multidrug-resistant Fusarium keratitis: diagnosis and treatment considerations.
AB - Mycotic keratitis is an ocular infective process derived from any fungal species
capable of corneal invasion. Despite its rarity in developed countries, its
challenging and elusive diagnosis may result in keratoplasty or enucleation
following failed medical management. Filamentous fungi such as Fusarium are often
implicated in mycotic keratitis. Bearing greater morbidity than its bacterial
counterpart, mycotic keratitis requires early clinical suspicion and initiation
of antifungal therapy to prevent devastating consequences. We describe a case of
multidrug-resistant mycotic keratitis in a 46-year-old man who continued to
decline despite maximal therapy and therapeutic keratoplasty. Finally,
enucleation was performed as a means of source control preventing dissemination
of a likely untreatable fungal infection into the orbit. Multidrug-resistant
Fusarium is rare, and may progress to endophthalmitis. We discuss potential
management options which may enhance diagnosis and outcome in this condition.
PMID- 27489067
TI - Single case of purple urine bag syndrome in an elderly woman with stroke.
AB - Purple urine bag syndrome is an unusual condition that heralds an underlying
urinary tract infection, in which certain bacteria produce a purple
discolouration within the catheter bag of affected cases. It is most often seen
in elderly women with constipation. While alarming, it can be resolved by
treating the infection causing it. This report presents an elderly patient who
developed the condition while an inpatient, and discusses the pathogenesis behind
the condition.
PMID- 27489068
TI - Lipoma of mandibular buccal vestibule: a case with histopathological literature
review.
AB - Lipoma is a tumour of soft tissue with rare occurrence in oral cavity accounting
for only 1-4% of benign oral tumours. Most common sites of involvement are the
buccal mucosa, tongue and floor of the mouth with typical presentation of an
asymptomatic, soft, smooth-surfaced, nodular and yellowish mass.
Histopathologically, a classical lipoma resembles normal adipose tissue and it
has multiple variants which are less commonly seen except fibrolipoma. The
article presents a case report of a relatively large oral classical lipoma in a
60-year-old man on a rare site, mandibular buccal vestibule, along with a review
of the literature and special emphasis on its various histopathological variants.
PMID- 27489069
TI - Renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in
Europe.
AB - Leprosy is a chronic infectious disease caused by Mycobacterium leprae The main
clinical manifestations involve the skin and the peripheral nervous system.
Several types of nephropathy have been described in leprosy. One frequent form of
renal involvement is amyloidosis, especially in patients with lepromatous
leprosy. In these patients, end-stage renal disease is an important contributor
to morbidity and mortality. Here, we present the case of a patient with nephrotic
syndrome caused by secondary amyloidosis, chronic peripheral neuropathy and a
history of leprosy. The patient was correctly treated in her youth, which is the
best way to avoid renal pathology, but she developed a nephrotic syndrome years
later.
PMID- 27489070
TI - New use for an old drug: oral ketamine for treatment-resistant depression.
AB - Treatment-resistant depression (TRD) is a disabling disorder that can interfere
with a patient's capacity to understand and participate in medical care and thus
negatively impact individual morbidity and mortality. Hospitalised patients with
TRD may require rapid alleviation of severe symptomatology, particularly when
suicidal or if unable to participate in care decisions. Ketamine is well known
for its anaesthetic effects and its use as a 'street' drug; however, its action
as an N-methyl-D-aspartate receptor antagonist makes ketamine a potential therapy
for TRD. The majority of studies investigating ketamine for TRD have used
intravenous drug delivery, demonstrating benefit for rapid alleviation and
sustained response of depression symptoms. Oral ketamine for urgent alleviation
of TRD symptoms is less reported. We describe rapid alleviation of severe TRD
with oral ketamine in a severely ill postoperative hospitalised patient, and
review the current literature on 'off-label' use of ketamine for treatment of
refractory depression.
PMID- 27489071
TI - A curious cause of appendicitis.
AB - A previously healthy 10-year-old boy presented to the emergency department with
central abdominal pain, loose stool and vomiting. He was diagnosed with
gastroenteritis, but was well enough to be discharged. The next day he reattended
with ongoing diarrhoea and vomiting, with the pain now localised to the right
iliac fossa (RIF). Acute appendicitis was suspected, and he was taken for
laparoscopic appendicectomy. At surgery, a gangrenous appendix was found, with
pus extending from the pelvis up to the liver. The appendix was excised and
thorough peritoneal washout performed. Postoperatively, he received 48 hours of
intravenous antibiotics and was discharged home. Unfortunately the boy presented
again 11 days later with right lower quadrant pain and fever. Ultrasound revealed
a collection in the RIF, and he returned to theatre for washout. His recovery was
slow until the peritoneal pus sent for bacterial culture grew Salmonella
enteritidis, identification of which facilitated appropriate antibiotic
treatment.
PMID- 27489072
TI - Rare cause of aortic regurgitation.
PMID- 27489073
TI - Morning glory anomaly with peripapillary staphyloma.
PMID- 27489074
TI - Controlled Coalescence of AlGaN Nanowire Arrays: An Architecture for Nearly
Dislocation-Free Planar Ultraviolet Photonic Device Applications.
AB - Nearly dislocation-free semipolar AlGaN templates are achieved on c-plane
sapphire substrate through controlled nanowire coalescence by selective-area
epitaxy. The coalesced Mg-doped AlGaN layers exhibit superior charge-carrier
transport properties. Semipolar-AlGaN ultraviolet light-emitting diodes
demonstrate excellent performance. This work establishes the use of engineered
nanowire structures as a viable architecture to achieve large-area, dislocation
free planar photonic and electronic devices.
PMID- 27489075
TI - Mortality in people with intellectual disabilities in England.
AB - BACKGROUND: People with intellectual disabilities (IDs) die at younger ages than
the general population, but nationally representative and internationally
comparable mortality data about people with ID, quantifying the extent and
pattern of the excess, have not previously been reported for England. METHOD: We
used data from the Clinical Practice Research Datalink database for April 2010 to
March 2014 (CPRD GOLD September 2015). This source covered several hundred
participating general practices comprising roughly 5% of the population of
England in the period studied. General practitioner (GP) records identified
people diagnosed by their GP as having ID. Linked national death certification
data allowed us to derive corresponding mortality data for people with and
without ID, overall and by cause. RESULTS: Mortality rates for people with ID
were significantly higher than for those without. Their all-cause standardised
mortality ratio was 3.18. Their life expectancy at birth was 19.7 years lower
than for people without ID. Circulatory and respiratory diseases and neoplasms
were the three most common causes of death for them. Cerebrovascular disease,
thrombophlebitis and pulmonary embolism all had standardised mortality ratios
greater than 3 in people with ID. This has not been described before. Other
potentially avoidable causes included epilepsy (3.9% of deaths), aspiration
pneumonitis (3.6%) and colorectal cancer (2.4%). Avoidable mortality analysis
showed a higher proportion of deaths from causes classified as amenable to good
medical care but a lower proportion from preventable causes compared with people
without ID. International comparison to areas for which data have been published
in sufficient detail for calculation of directly standardised rates suggest
England may have higher death rates for people with ID than areas in Canada and
Finland, and lower death rates than Ireland or the State of Massachusetts in the
USA. CONCLUSIONS: National data about mortality in people with ID provides a
basis for public health interventions. Linked data using GP records to identify
people with ID could provide comprehensive population-based monitoring in
England, unbiased by the circumstances of illnesses or death; to date information
governance constraints have prevented this. However, GPs in England currently
identify only around 0.5% of the population as having ID, suggesting that
individuals with mild, non-syndromic ID are largely missed. Notably common causes
of death suggest control of cardiovascular risk factors, epilepsy and dysphagia,
management of thrombotic risks and colorectal screening are important areas for
health promotion initiatives.
PMID- 27489076
TI - Pharmacokinetics and metabolism of [14C]-tozadenant (SYN-115), a novel A2a
receptor antagonist ligand, in healthy volunteers.
AB - 1. This phase-I study (NCT02240290) was designed to investigate the human
absorption, disposition and mass balance of 14C-tozadenant, a novel A2a receptor
antagonist in clinical development for Parkinson s disease. 2. Six healthy male
subjects received a single oral dose of tozadenant (240 mg containing 81.47 KBq
of [14C]-tozadenant). Blood, urine and feces were collected over 14 days.
Radioactivity was determined by liquid scintillation counting or accelerator mass
spectrometry (AMS). Tozadenant and metabolites were characterized using HPLC
MS/MS and HPLC-AMS with fraction collection. 3. At 4 h, the Cmax of tozadenant
was 1.74 MUg/mL and AUC(0-t) 35.0 h MUg/mL, t1/2 15 h, Vz/F 1.82 L/kg and CL/F
1.40 mL/min/kg. For total [14C] radioactivity, the Cmax was 2.29 MUg eq/mL at 5 h
post-dose and AUC(0-t) 43.9 h MUg eq/mL. Unchanged tozadenant amounted to 93% of
the radiocarbon AUC(0-48h). At 312 h post-dose, cumulative urinary and fecal
excretion of radiocarbon reached 30.5% and 55.1% of the dose, respectively.
Unchanged tozadenant reached 11% in urine and 12% of the dose in feces.
Tozadenant was excreted as metabolites, including di-and mono-hydroxylated
metabolites, N/O dealkylated metabolites, hydrated metabolites. 4. The only
identified species circulating in plasma was unchanged tozadenant. Tozadenant was
primarily excreted in urine and feces in the form of metabolites.
PMID- 27489078
TI - A proactive task set influences how response inhibition is implemented in the
basal ganglia.
AB - Increasing a participant's ability to prepare for response inhibition is known to
result in longer Go response times and is thought to engage a "top-down fronto
striatal inhibitory task set." This premise is supported by the observation of
anterior striatum activation in functional magnetic resonance imaging (fMRI)
analyses that focus on uncertain versus certain Go trials. It is assumed that
setting up a proactive inhibitory task set also influences how participants
subsequently implement stopping. To assess this assumption, we aimed to
manipulate the degree of proactive inhibition in a modified stop-signal task to
see how this manipulation influences activation when reacting to the Stop cue.
Specifically, we tested whether there is differential activity of basal ganglia
nuclei, namely the subthalamic nucleus (STN) and anterior striatum, on Stop
trials when stop-signal probability was relatively low (20%) or high (40%).
Successful stopping was associated with increased STN activity when Stop trials
were infrequent and increased caudate head activation when Stop trials were more
likely, suggesting a different implementation of reactive response inhibition by
the basal ganglia for differing degrees of proactive response control. Hum Brain
Mapp 37:4706-4717, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27489077
TI - The Effect of Guided Web-Based Cognitive Behavioral Therapy on Patients With
Depressive Symptoms and Heart Failure: A Pilot Randomized Controlled Trial.
AB - BACKGROUND: Depressive symptoms, and the associated coexistence of symptoms of
anxiety and decreased quality of life (QoL), are common in patients with heart
failure (HF). However, treatment strategies for depressive symptoms in patients
with HF still remain to be established. Internet-based cognitive behavioral
therapy (ICBT), as guided self-help CBT programs, has shown good effects in the
treatment of depression. Until now, ICBT has not been evaluated in patients with
HF with depressive symptoms. OBJECTIVE: The aims of this study were to (1)
evaluate the effect of a 9-week guided ICBT program on depressive symptoms in
patients with HF; (2) investigate the effect of the ICBT program on cardiac
anxiety and QoL; and (3) assess factors associated with the change in depressive
symptoms. METHODS: Fifty participants were randomized into 2 treatment arms: ICBT
or a Web-based moderated discussion forum (DF). The Patient Health Questionnaire
9 was used to measure depressive symptoms, the Cardiac Anxiety Questionnaire
(CAQ) was used to measure cardiac-related anxiety, and the Minnesota Living with
Heart Failure questionnaire was used to measure QoL. Data were collected at
baseline and at follow-up at the end of the 9-week intervention. Intention-to
treat analysis was used, and missing data were imputed by the Expectation
Maximization method. Between-group differences were determined by analysis of
covariance with control for baseline score and regression to the mean. RESULTS:
No significant difference in depressive symptoms between the ICBT and the DF
group at the follow-up was found, [F(1,47)=1.63, P=.21] and Cohen's d=0.26.
Secondary within-group analysis of depressive symptoms showed that such symptoms
decreased significantly in the ICBT group from baseline to the follow-up
(baseline M=10.8, standard deviation [SD]=5.7 vs follow-up M=8.6, SD=4.6,
t(24)=2.6, P=.02, Cohen's d=0.43), whereas in the DF group, there was no
significant change (baseline M=10.6, SD=5.0, vs follow-up M=9.8, SD=4.3,
t(24)=0.93, P=.36. Cohen's d=0.18). With regard to CAQ and QoL no significant
differences were found between the groups (CAQ [d(1,47)=0.5, P=.48] and QoL
[F(1,47)=2.87, P=.09]). In the ICBT group in the CAQ subscale of fear, a
significant within-group decrease was shown (baseline M=1.55 vs follow-up M=1.35,
P=.04). In the ICBT group, the number of logins to the Web portal correlated
significantly with improvement in depressive symptoms (P=.02), whereas higher age
(P=.01) and male sex (P=.048) were associated with less change in depressive
symptoms. This study is underpowered because of difficulties in the recruitment
of patients. CONCLUSIONS: Guided ICBT adapted for persons with HF and depressive
symptoms was not statistically superior to participation in a Web-based DF.
However, within the ICBT group, a statically significant improvement of
depressive symptoms was detected. CLINICALTRIAL: Clinicaltrials.gov NCT01681771;
https://clinicaltrials.gov/ct2/show/NCT01681771 (Archived by WebCite at
http://www.webcitation.org/6ikzbcuLN).
PMID- 27489079
TI - Oxidative stress status in Chinese women with different clinical phenotypes of
polycystic ovary syndrome.
AB - OBJECTIVE: To determine oxidative stress status and its association with clinical
and metabolic parameters in Chinese women with different clinical phenotypes of
polycystic ovary syndrome (PCOS). DESIGN: A cross-sectional study. PATIENTS: A
total of 544 patients with PCOS and 468 control women were included.
MEASUREMENTS: The total oxidant status (TOS) was determined using a microplate
colorimetric method. Total antioxidant capacity (T-AOC), oxidative stress index
(OSI, the ratios of TOS to T-AOC) and clinical, hormonal and metabolic parameters
were also analysed. RESULTS: TOS and OSI were significantly higher in each of the
four PCOS phenotypes based on the Rotterdam criteria than in the control women
and higher in patients with hyperandrogenism (HA) than in those without HA (P <
0.05). TOS, T-AOC and OSI were higher in lean patients than in lean controls (P <
0.05). These values, except OSI, were also higher in overweight/obese patients
than in lean patients, and lean or overweight/obese controls (P < 0.05).
Multivariate regression analysis demonstrated that apolipoprotein (apo)A1, the
Ferriman-Gallwey score, triglyceride (TG), oestradiol (E2 ), high-density
lipoprotein cholesterol (HDL-C) and 2-h glucose levels were the main predictors
of TOS; the Ferriman-Gallwey score, E2 , apoA1, TG and HDL-C levels were the main
predictors of OSI. CONCLUSIONS: Patients with PCOS with HA have higher oxidative
stress levels compared with those without HA. The increased oxidative stress in
PCOS is related to HA status, increased plasma glucose, TG, HDL-C and E2 levels,
decreased apoA1 concentrations and a relative shortage of antioxidant capacity.
PMID- 27489080
TI - Why metal-oxos react with dihydroanthracene and cyclohexadiene at comparable
rates, despite having different C-H bond strengths. A computational study.
AB - 1,4-Cyclohexadiene (CHD) and 9,10-dihydroanthracene (DHA) are two substrates used
to probe the steric requirements of metal-oxo oxidants in H-atom-transfer (HAT)
reactions, based on the assumption that they have comparable C-H bond
dissociation enthalpies (BDEs). We use computations to demonstrate that the BDE
of DHA is ~3.5 kcal mol(-1) larger than that of CHD and that their often
comparable reactivity is based on a competing interplay of bond strengths and
favorable van der Waals interactions.
PMID- 27489082
TI - Actual lowering effect of metabolic syndrome on serum prostate-specific antigen
levels is partly concealed by enlarged prostate: results from a large-scale
population-based study.
AB - OBJECTIVES: To clarify the lowering effect of metabolic syndrome (MetS) on serum
prostate-specific antigen (PSA) levels in a Chinese screened population. SUBJECTS
AND METHODS: A total of 45 540 ostensibly healthy men aged 55-69 years who
underwent routine health check-ups at Beijing Shijitan Hospital between 2008 and
2015 were included in the study. All the men underwent detailed clinical
evaluations. PSA mass density was calculated (serum PSA level * plasma volume /
prostate volume) for simultaneously adjusting plasma volume and prostate volume.
According to the modified National Cholesterol Education Programme-Adult
Treatment Panel (NCEP-ATP) III criteria, patients were dichotomized by the
presence of MetS, and differences in PSA density and PSA mass density were
compared between groups. Linear regression analysis was used to evaluate the
effect of MetS on serum PSA levels. RESULTS: When larger prostate volume in men
with MetS was adjusted for, both PSA density and PSA mass density in men with
MetS were significantly lower than in men without MetS, and the estimated
difference in mean serum PSA level between men with and without MetS was greater
than that before adjusting for prostate volume. In the multivariate regression
model, the presence of MetS was independently associated with an 11.3% decline in
serum PSA levels compared with the absence of MetS. In addition, increasing
number of positive MetS components was significantly and linearly associated with
decline in serum PSA levels. CONCLUSION: The actual lowering effect of MetS on
serum PSA levels was partly concealed by the enlarged prostate in men with MetS,
and the presence of MetS was independently associated with lower serum PSA
levels. Urologists need to be aware of the effect of MetS on serum PSA levels and
should discuss this subject with their patients.
PMID- 27489081
TI - Activation of liver X receptor attenuates lysophosphatidylcholine-induced IL-8
expression in endothelial cells via the NF-kappaB pathway and SUMOylation.
AB - The liver X receptor (LXR) is a cholesterol-sensing nuclear receptor that has an
established function in lipid metabolism; however, its role in inflammation is
elusive. In this study, we showed that the LXR agonist GW3965 exhibited potent
anti-inflammatory activity by suppressing the firm adhesion of monocytes to
endothelial cells. To further address the mechanisms underlying the inhibition of
inflammatory cell infiltration, we evaluated the effects of LXR agonist on
interleukin-8 (IL-8) secretion and nuclear factor-kappa B (NF-kappaB) activation
in human umbilical vein endothelial cells (HUVECs). The LXR agonist significantly
inhibited lysophosphatidylcholine (LPC)-induced IL-8 production in a dose
dependent manner without appreciable cytotoxicity. Western blotting and the NF
kappaB transcription activity assay showed that the LXR agonist inhibited p65
binding to the IL-8 promoter in LPC-stimulated HUVECs. Interestingly, knockdown
of the indispensable small ubiquitin-like modifier (SUMO) ligases Ubc9 and
Histone deacetylase 4 (HDAC4) reversed the increase in IL-8 induced by LPC.
Furthermore, the LPC-induced degradation of inhibitory kappaBalpha was delayed
under the conditions of deficient SUMOylation or the treatment of LXR agonist.
After enhancing SUMOylation by knockdown SUMO-specific protease Sentrin-specific
protease 1 (SENP1), the inhibition of GW3965 was rescued on LPC-mediated IL-8
expression. These findings indicate that LXR-mediated inflammatory gene
repression correlates to the suppression of NF-kappaB pathway and SUMOylation.
Our results suggest that LXR agonist exerts the anti-atherosclerotic role by
attenuation of the NF-kappaB pathway in endothelial cells.
PMID- 27489083
TI - Fate of Enlarged Iliac Arteries After Endovascular or Open Abdominal Aortic
Aneurysm Repair.
AB - PURPOSE: To examine the fate of untreated ectatic and aneurysmal common iliac
arteries (CIAs) after open treatment and endovascular aneurysm repair (EVAR) of
abdominal aortic aneurysm (AAA). METHODS: Databases of scientific literature were
searched between January 1980 and February 2016 to identify publications on the
follow-up of ectatic and aneurysmal CIAs after open or endovascular AAA repair.
The primary outcome measure was the increase of iliac artery diameter during
follow-up. The secondary outcome was the subsequent reintervention rate during
follow-up. RESULTS: Only 3 open AAA and 3 EVAR studies containing 1239 patients
met the inclusion criteria for analysis. In the open AAA group, ectatic iliac
arteries (defined as 12-18 mm) had a diameter progression of 1.7 to 1.8 mm during
a follow-up period of 51.6 to 85.2 months. The aneurysmal iliac arteries (>18 mm)
in the open repair group showed a faster growth (2.3-3.0 mm) in a follow-up
period of 50.4 to 85.2 months. The pooled assessment of arteries >=18 mm had a
mean growth of 2.56 mm at 60 months of follow-up. In the entire open AAA cohort,
the reintervention rate for CIA transformation was <1%. In the EVAR studies,
arbitrary cutoff sizes of 16 to 20 mm for ectatic arteries and >20 mm for
aneurysmal arteries were used. During a follow-up of 39.2 to 60 months, the
diameter progression was 1.5 mm for the 16-mm iliac arteries and 2.7 mm for the
20-mm iliac arteries. The need for endovascular reinterventions was similar in
patients with previously normal or enlarged CIAs. CONCLUSION: After open AAA
repair, the overall size of CIA aneurysms grows slowly, but enlarged CIAs >20 mm
in EVAR patients show faster growth during follow-up. However, the need for
secondary interventions was similar in patients with normal or enlarged CIAs post
EVAR.
PMID- 27489084
TI - Commentary: Challenging Anatomy and Mortality After Endovascular Treatment of
Ruptured Aortic Aneurysm: Proceed With Caution When Treating the Hostile Neck.
PMID- 27489085
TI - Autoimmune progesterone dermatitis: Case report of an unexpected treatment
reaction.
AB - Autoimmune progesterone dermatitis (APD) is a rare skin condition with a varying
morphology, which appears on a monthly basis during the luteal phase of the
menstrual cycle and resolves spontaneously with the endogenous decrease in
progesterone during menses. We present the case of 39-year-old multiparous
Caucasian woman with generalised, self-limited urticaria in her perimenstrual
period. APD was diagnosed in light of the cyclical nature of the symptoms. An
intradermal test with the administration of 0.5 mg/mL of medroxyprogesterone
acetate showed a positive result. She started using vaginal hormonal
contraceptive that paradoxically exacerbate the symptoms, which ceased after the
removal of the device. An oral combined contraceptive was initiated instead, with
complete resolution of the symptoms. We share the case because of the rarity of
the situation, emphasising the importance of a multidisciplinary team for
differential diagnosis and patient follow up.
PMID- 27489086
TI - Pleomorphic lobular carcinoma of the breast: a comparison of cytopathological
features with other lobular carcinoma variants.
AB - OBJECTIVE: Pleomorphic lobular carcinoma (PLC) is a subtype of breast cancer with
unique morphological features, but it remains controversial whether PLC should be
considered an independent disease entity. The aim of this study was to illustrate
cytopathological characteristics of PLC in comparison with other lobular
carcinoma variants. METHODS: We investigated clinicopathological features of PLC
(n = 11) compared with those of other variants of invasive lobular carcinoma
(ILC, non-PLC) (n = 32). Histological variants of the non-PLC group consisted of
classic (n = 25), solid (n = 2), alveolar (n = 1) and a tubulolobular type (n =
4). A review of cytological reports and fine needle aspiration (FNA) smear
samples was performed for the PLC (n = 9) and non-PLC (n = 27) groups. RESULTS:
Patients with PLC were older, and had a higher nuclear grade and a higher
incidence of axillary lymph node metastasis and triple negative phenotype than
non-PLC patients (P = 0.007, P < 0.001, P = 0.02 and P < 0.001, respectively).
Cytological findings in PLC included medium- to large-sized nuclei, prominent
nucleoli, a moderate-to-severe degree of pleomorphism, apocrine change and
background necrosis, none of which were evident in the smears of the non-PLC
group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, and P = 0.03, respectively).
Despite these differences, patients with PLC and non-PLC showed similar clinical
outcomes in our follow-up period. CONCLUSIONS: Based on our results, a
cytological diagnosis of PLC should be proposed if there are moderate- to large
sized nuclei, prominent nucleoli, a moderate-to severe degree of nuclear
pleomorphism, apocrine change and necrosis in the background in FNA biopsy
samples.
PMID- 27489087
TI - Assessing the Quality of Economic Evaluations of FDA Novel Drug Approvals: A
Systematic Review.
AB - OBJECTIVE: To systematically review and assess the quality of the novel drugs'
economic evaluation literature in print during the drugs' early commercial
availability following US regulatory approval. DATA SOURCES: MEDLINE and the
United Kingdom National Health Service Economic Evaluation Database were searched
from 1946 through December 2011 for economic evaluations of the 50 novel drugs
approved by the FDA in 2008 and 2009. STUDY SELECTION AND DATA EXTRACTION: The
inclusion criteria were English-language, peer-reviewed, original economic
evaluations (cost-utility, cost-effectiveness, cost-minimization, and cost
benefit analyses). We extracted and analyzed data from 36 articles considering 19
of the 50 drugs. Two reviewers assessed each publication's quality using the
Quality of Health Economic Studies (QHES) instrument and summarized study quality
on a 100-point scale. DATA SYNTHESIS: Study quality had a mean of 70.0 +/- 16.2
QHES points. The only study characteristics associated with QHES score (with P <
0.05) were having used modeling or advanced statistics, 75.1 versus 61.9 without;
using quality-adjusted life years as an outcome, 75.9 versus 64.7 without; and
cost-utility versus cost-minimization analysis, 75.9 versus 58.7. Studies most
often satisfied quality aspects about stating study design choices and least
often satisfied aspects about justifying design choices. CONCLUSION: The reviewed
literature considered a minority of the 2008-2009 novel drugs and had mixed study
quality. Cost-effectiveness stakeholders might benefit from efforts to improve
the quality and quantity of literature examining novel drugs. Editors and
reviewers may support quality improvement by stringently imposing economic
evaluation guidelines about justifying study design choices.
PMID- 27489088
TI - Cannabinoid Hyperemesis Syndrome: A Paradoxical Case.
PMID- 27489090
TI - On understanding the self of the schizophrenics.
AB - Identified as a mental disorder by Emil Kraepelin and Eugen Bleuler (1858-1939),
schizophrenia has been subject to various criticisms, on both political and
scientific grounds. Still, until the latest edition of the Diagnostic and
Statistical Manual of Mental Disorders, DSM-5, as the'Spectrum of Schizophrenia
and Other Psychotic Disorders'. In this article, we will assume a neutral
conception of 'mental disorder' and describe schizophrenia broadly as a kind of
altered state of consciousness. The alteration is so radical that some authors
argue schizophrenia resists any attempt at being comprehended and that the only
possible explanation for its occurrence is causal-mechanical. This idea that
schizophrenia does not allow for any degree of understanding goes back to
Jaspers, the founder of Psychopathology. The aim of this article is to show that,
although emerging from the same line of thought of Jaspers, the more recent
phenomenologists who revisit classical Phenomenology, overcome the barrier
between explaining and understanding. The argument here is that schizophrenia can
be at least partially understood if we maintain an open mind towards people who
do not share part of our world.
PMID- 27489089
TI - Mediation Analysis for Health Disparities Research.
AB - Social epidemiologists often seek to determine the mechanisms that underlie
health disparities. This work is typically based on mediation procedures that may
not be justified with exposures of common interest in social epidemiology. In
this analysis, we explored the consequences of using standard approaches,
referred to as the difference and generalized product methods, when mediator
outcome confounders are associated with the exposure. We compared these with
inverse probability-weighted marginal structural models, the structural
transformation method, doubly robust g-estimation of a structural nested model,
and doubly robust targeted minimum loss-based estimation. We used data on 900,726
births from 2003 to 2007 in the Penn Moms study, conducted in Pennsylvania, to
assess the extent to which breastfeeding prior to hospital discharge explained
the racial disparity in infant mortality. Overall, for every 1,000 births, 3.36
more infant deaths occurred among non-Hispanic black women relative to all other
women (95% confidence interval: 2.78, 3.93). Using the difference and generalized
product methods to assess the disparity that would remain if everyone breastfed
prior to discharge suggested a complete elimination of the disparity (risk
difference = -0.87 per 1,000 births; 95% confidence interval: -1.39, -0.35). In
contrast, doubly robust methods suggested a reduction in the disparity to 2.45
(95% confidence interval: 2.20, 2.71) more infant deaths per 1,000 births among
non-Hispanic black women. Standard approaches for mediation analysis in health
disparities research can yield misleading results.
PMID- 27489091
TI - A Fatal Case of a Ruptured Cerebral Aneurysm Detected by Postmortem Computed
Tomography Angiography Using a New Contrast-Medium Solution.
AB - Forensic autopsy is still the criterion standard in legal investigations.
Currently, notable transformation is occurring because postmortem imaging is
being increasingly endorsed. This article highlights the effectiveness of
postmortem computed tomography angiography by using a new contrast medium mixture
as a solitary tool to define the cause and manner of death in a ruptured cerebral
aneurysm case. Based on the imaging results, autopsy was not mandated and the
case was closed.
PMID- 27489092
TI - Negative Aging Attitudes Predict Greater Reactivity to Daily Stressors in Older
Adults.
AB - Objectives: In order to understand conflicting findings regarding the emotional
reactions of older adults to daily stressors, we examined the possibility that
negative aging attitudes could function as an important individual differences
factor related to stressor reactivity. Method: Using a daily dairy design, we
examined the aging attitudes of 43 older adults reporting on 380 total days.
Participants reported their aging attitudes on Day 1, followed by their stressor
exposure and negative affect on Days 2-9. Covariates included age, gender,
education, and personality. Results: Using multilevel modeling, our results
suggest that individuals with more positive aging attitudes report consistent
levels of affect across study days regardless of stressors, whereas those with
more negative aging attitudes reported increased emotional reactivity to daily
stressors. Discussion: Positive aging attitudes may serve as a resource that
helps buffer reactions to daily stressors.
PMID- 27489093
TI - Abstracts Presented at the Joint Summer Meeting of the British Association of
Clinical Anatomists, the European Association for Clinical Anatomy and the
Sociedad Anatomica Espanola on 24th-27th June 2015 at the Medicine and Pharmacy
Faculty, Rouen, France.
PMID- 27489094
TI - Prosopagnosia as unusual presentation of semantic dementia: a case study.
AB - OBJECT: Semantic dementia is one of the main clinical variants of frontotemporal
dementia and it is characterized by severe loss of conceptual knowledge with
relative preservation of other cortical abilities. METHODS: We described a case
of a patient affected by right temporal variant of frontotemporal lobar
degeneration, characterized by prosopagnosia as an unusual disease onset.
RESULTS: The neuropsychological evaluation showed a progressive deficit in face
recognition and a slow decline in language in the absence of behavioral
alterations. Magnetic resonance imaging showed diffuse vascular ischemic lesions,
cortical atrophy in bilateral temporal lobes, and a marked bilateral decrease
hippocampal volume, mainly involving the right side. CONCLUSIONS: Our findings
suggest that prosopagnosia could be a predictive marker of atypical semantic
dementia onset.
PMID- 27489095
TI - Epidemiological and Evolutionary Inference of the Transmission Network of the
2014 Highly Pathogenic Avian Influenza H5N2 Outbreak in British Columbia, Canada.
AB - The first North American outbreak of highly pathogenic avian influenza (HPAI)
involving a virus of Eurasian A/goose/Guangdong/1/1996 (H5N1) lineage began in
the Fraser Valley of British Columbia, Canada in late November 2014. A total of
11 commercial and 1 non-commercial (backyard) operations were infected before the
outbreak was terminated. Control measures included movement restrictions that
were placed on a total of 404 individual premises, 150 of which were located
within a 3 km radius of an infected premise(s) (IP). A complete epidemiological
investigation revealed that the source of this HPAI H5N2 virus for 4 of the
commercial IPs and the single non-commercial IP likely involved indirect contact
with wild birds. Three IPs were associated with the movement of birds or service
providers and localized/environmental spread was suspected as the source of
infection for the remaining 4 IPs. Viral phylogenies, as determined by Bayesian
Inference and Maximum Likelihood methods, were used to validate the
epidemiologically inferred transmission network. The phylogenetic clustering of
concatenated viral genomes and the median-joining phylogenetic network of the
viruses supported, for the most part, the transmission network that was inferred
by the epidemiologic analysis.
PMID- 27489096
TI - Macrophage polarization in experimental and clinical choroidal
neovascularization.
AB - Macrophages play an important role in the development of age-related macular
degeneration (AMD). In this study, the spatial and temporal changes and the
polarization of macrophages in murine laser-induced choroidal neovascularization
(CNV) were investigated, and the polarized M1 and M2 biomarkers in the aqueous
humors of neovascular AMD (nAMD) patients were studied. Macrophages, the main
infiltrating inflammatory cells in CNV lesions, were evidenced by a significant
increase in F4/80 mRNA expression and by the infiltration of F4/80+ cells in the
lesions and the vicinity of laser-induced CNV. The mRNA expressions of M1-related
markers were dramatically upregulated in the early stage, while the M2-related
markers were slightly upregulated in the middle stage and sustained until the
late stage. The results of immunostaining showed a similar early-but-transient M1
pattern and a delayed-but-sustained M2 pattern in laser-induced CNV. In addition,
a higher M2/M1 ratio was found in both the murine models (Arg-1/iNOS and
CCL22/CXCL10) and the aqueous humors of nAMD patients (CCL22/CXCL10) than in the
controls. Our results suggested that the dynamic patterns of M1 and M2 were
different in both the experimental and clinical CNV. The M2 macrophages were
predominant and may play a more important role in the development of CNV.
PMID- 27489098
TI - Three-Dimensional Ni2P Nanoarray: An Efficient Catalyst Electrode for Sensitive
and Selective Nonenzymatic Glucose Sensing with High Specificity.
AB - It is highly attractive to construct a natural enzyme-free electrode for
sensitive and selective detection of glucose. In this Letter, we report that a
Ni2P nanoarray on conductive carbon cloth (Ni2P NA/CC) behaves as an efficient
three-dimensional catalyst electrode for glucose electrooxidation under alkaline
conditions. Electrochemical measurements demonstrate that the Ni2P NA/CC, when
used as a nonenzymatic glucose sensor, offers superior analytical performances
with a short response time of 5 s, a wide detection range of 1 MUM to 3 mM, a low
detection limit of 0.18 MUM (S/N = 3), a response sensitivity of 7792 MUA mM(-1)
cm(-2), and satisfactory selectivity, specificity, and reproducibility. Moreover,
it can also be used for glucose detection in human blood serum, promising its
application toward determination of glucose in real samples.
PMID- 27489097
TI - Xenomicrobiology: a roadmap for genetic code engineering.
AB - Biology is an analytical and informational science that is becoming increasingly
dependent on chemical synthesis. One example is the high-throughput and low-cost
synthesis of DNA, which is a foundation for the research field of synthetic
biology (SB). The aim of SB is to provide biotechnological solutions to health,
energy and environmental issues as well as unsustainable manufacturing processes
in the frame of naturally existing chemical building blocks. Xenobiology (XB)
goes a step further by implementing non-natural building blocks in living cells.
In this context, genetic code engineering respectively enables the re-design of
genes/genomes and proteins/proteomes with non-canonical nucleic (XNAs) and amino
(ncAAs) acids. Besides studying information flow and evolutionary innovation in
living systems, XB allows the development of new-to-nature therapeutic
proteins/peptides, new biocatalysts for potential applications in synthetic
organic chemistry and biocontainment strategies for enhanced biosafety. In this
perspective, we provide a brief history and evolution of the genetic code in the
context of XB. We then discuss the latest efforts and challenges ahead for
engineering the genetic code with focus on substitutions and additions of ncAAs
as well as standard amino acid reductions. Finally, we present a roadmap for the
directed evolution of artificial microbes for emancipating rare sense codons that
could be used to introduce novel building blocks. The development of such
xenomicroorganisms endowed with a 'genetic firewall' will also allow to study and
understand the relation between code evolution and horizontal gene transfer.
PMID- 27489099
TI - Time-frequency distribution properties of event-related potentials in mental
fatigue induced by visual memory tasks.
AB - Prolonged periods of demanding cognitive tasks lead to an exhausted feeling known
as mental fatigue. The neural underpinnings of mental fatigue are still under
exploration. In the present study, we aimed to identify neurophysiological
indicators of mental fatigue by studying the time-frequency distribution of the
event-related potentials (ERPs) measured in N=26 adults in nonfatigued versus
fatigued states. We were interested in the frontal theta and occipital alpha
variations, which have shown consistent relationships with mental fatigue in
previous studies. Furthermore, we expected differential changes in left and right
electrodes, in line with previously detected lateralization effects in cognitive
tasks. Mental fatigue was induced by a sustained two-back verbal visual memory
task for 125 min and assessed using the Chalder Fatigue Scale. We applied a high
resolution time-frequency analysis method called smoothed pseudo Wigner Ville
distribution and used regional integrals as indicators for changing trends of
signal energy. Results showed an increase in ERP frontal theta energy (P=0.03)
and a decrease in occipital alpha energy (P=0.028) when participants became
mentally fatigued. The change in frontal theta was more pronounced in left
electrode sites (P=0.032), hinting toward a differential fatigue effect in the
two hemispheres. The results were discussed on the basis of previous
lateralization studies with memory tasks and interpreted as an indicator of a
causal relationship between the sustained task execution and the physiological
changes. Our findings also suggest that the ERP signal energy variations in
frontal theta and occipital alpha might be used as neural biomarkers to assess
mental fatigue.
PMID- 27489100
TI - Can color changes alter the neural correlates of recognition memory? Manipulation
of processing affects an electrophysiological indicator of conceptual implicit
memory.
AB - It has been widely shown that recognition memory includes two distinct retrieval
processes: familiarity and recollection. Many studies have shown that recognition
memory can be facilitated when there is a perceptual match between the studied
and the tested items. Most event-related potential studies have explored the
perceptual match effect on familiarity on the basis of the hypothesis that the
specific event-related potential component associated with familiarity is the
FN400 (300-500 ms mid-frontal effect). However, it is currently unclear whether
the FN400 indexes familiarity or conceptual implicit memory. In addition, on the
basis of the findings of a previous study, the so-called perceptual manipulations
in previous studies may also involve some conceptual alterations. Therefore, we
sought to determine the influence of perceptual manipulation by color changes on
recognition memory when the perceptual or the conceptual processes were
emphasized. Specifically, different instructions (perceptually or conceptually
oriented) were provided to the participants. The results showed that color
changes may significantly affect overall recognition memory behaviorally and that
congruent items were recognized with a higher accuracy rate than incongruent
items in both tasks, but no corresponding neural changes were found. Despite the
evident familiarity shown in the two tasks (the behavioral performance of
recognition memory was much higher than at the chance level), the FN400 effect
was found in conceptually oriented tasks, but not perceptually oriented tasks. It
is thus highly interesting that the FN400 effect was not induced, although color
manipulation of recognition memory was behaviorally shown, as seen in previous
studies. Our findings of the FN400 effect for the conceptual but not perceptual
condition support the explanation that the FN400 effect indexes conceptual
implicit memory.
PMID- 27489101
TI - Highly Conformal Deposition of an Ultrathin FeOOH Layer on a Hematite
Nanostructure for Efficient Solar Water Splitting.
AB - An ultrathin (ca. 2 nm) amorphous FeOOH overlayer was deposited conformally on a
hematite nanostructure by a simple solution-based precipitation method, to
generate an oxygen evolution cocatalyst for efficient solar water splitting. This
uniform and highly conformal coating of the ultrathin metal oxyhydroxide is rare
and is distinguished from the layers prepared by other conventional methods. With
the FeOOH overlayer as the cocatalyst, the water oxidation photocurrent of
hematite increased by a factor of approximately two and the onset potential
shifted in the cathodic direction by 0.12 V under 1 sun illumination. The
enhanced performance was attributed to the improved water oxidation kinetics and
the passivation of the surface states of the hematite.
PMID- 27489102
TI - Activation of the Human Epithelial Sodium Channel (ENaC) by Bile Acids Involves
the Degenerin Site.
AB - The epithelial sodium channel (ENaC) is a member of the ENaC/degenerin ion
channel family, which also includes the bile acid-sensitive ion channel (BASIC).
So far little is known about the effects of bile acids on ENaC function. ENaC is
probably a heterotrimer consisting of three well characterized subunits
(alphabetagamma). In humans, but not in mice and rats, an additional delta
subunit exists. The aim of this study was to investigate the effects of
chenodeoxycholic, cholic, and deoxycholic acid in unconjugated (CDCA, CA, and
DCA) and tauro-conjugated (t-CDCA, t-CA, t-DCA) form on human ENaC in its
alphabetagamma- and deltabetagamma-configuration. We demonstrated that tauro
conjugated bile acids significantly stimulate ENaC in the alphabetagamma- and in
the deltabetagamma-configuration. In contrast, non-conjugated bile acids have a
robust stimulatory effect only on deltabetagammaENaC. Bile acids stimulate ENaC
mediated currents by increasing the open probability of active channels without
recruiting additional near-silent channels known to be activated by proteases.
Stimulation of ENaC activity by bile acids is accompanied by a significant
reduction of the single-channel current amplitude, indicating an interaction of
bile acids with a region close to the channel pore. Analysis of the known ASIC1
(acid-sensing ion channel) crystal structure suggested that bile acids may bind
to the pore region at the degenerin site of ENaC. Substitution of a single amino
acid residue within the degenerin region of betaENaC (N521C or N521A)
significantly reduced the stimulatory effect of bile acids on ENaC, suggesting
that this site is critical for the functional interaction of bile acids with the
channel.
PMID- 27489103
TI - The CaVbeta Subunit Protects the I-II Loop of the Voltage-gated Calcium Channel
CaV2.2 from Proteasomal Degradation but Not Oligoubiquitination.
AB - CaVbeta subunits interact with the voltage-gated calcium channel CaV2.2 on a site
in the intracellular loop between domains I and II (the I-II loop). This
interaction influences the biophysical properties of the channel and leads to an
increase in its trafficking to the plasma membrane. We have shown previously that
a mutant CaV2.2 channel that is unable to bind CaVbeta subunits (CaV2.2 W391A)
was rapidly degraded (Waithe, D., Ferron, L., Page, K. M., Chaggar, K., and
Dolphin, A. C. (2011) J. Biol. Chem. 286, 9598-9611). Here we show that, in the
absence of CaVbeta subunits, a construct consisting of the I-II loop of CaV2.2
was directly ubiquitinated and degraded by the proteasome system. Ubiquitination
could be prevented by mutation of all 12 lysine residues in the I-II loop to
arginines. Including a palmitoylation motif at the N terminus of CaV2.2 I-II loop
was insufficient to target it to the plasma membrane in the absence of CaVbeta
subunits even when proteasomal degradation was inhibited with MG132 or
ubiquitination was prevented by the lysine-to-arginine mutations. In the presence
of CaVbeta subunit, the palmitoylated CaV2.2 I-II loop was protected from
degradation, although oligoubiquitination could still occur, and was efficiently
trafficked to the plasma membrane. We propose that targeting to the plasma
membrane requires a conformational change in the I-II loop that is induced by
binding of the CaVbeta subunit.
PMID- 27489104
TI - The Nuclear Protein IkappaBzeta Forms a Transcriptionally Active Complex with
Nuclear Factor-kappaB (NF-kappaB) p50 and the Lcn2 Promoter via the N- and C
terminal Ankyrin Repeat Motifs.
AB - The nuclear protein IkappaBzeta, comprising the N-terminal trans-activation
domain and the C-terminal ankyrin repeat (ANK) domain composed of seven ANK
motifs, activates transcription of a subset of nuclear factor-kappaB (NF-kappaB)
dependent innate immune genes such as Lcn2 encoding the antibacterial protein
lipocalin-2. Lcn2 activation requires formation of a complex containing
IkappaBzeta and NF-kappaB p50, a transcription factor that harbors the DNA
binding Rel homology region but lacks a trans-activation domain, on the promoter
with the canonical NF-kappaB-binding site (kappaB site) and its downstream
cytosine-rich element. Here we show that IkappaBzeta productively interacts with
p50 via Asp-451 in the N terminus of ANK1, a residue that is evolutionarily
conserved among IkappaBzeta and the related nuclear IkappaB proteins Bcl-3 and
IkappaBNS Threonine substitution for Asp-451 abrogates direct association with
the kappaB-site-binding protein p50, complex formation with the Lcn2 promoter
DNA, and activation of Lcn2 transcription. The basic residues Lys-717 and Lys-719
in the C-terminal region of ANK7 contribute to IkappaBzeta binding to the Lcn2
promoter, probably via interaction with the cytosine-rich element required for
Lcn2 activation; glutamate substitution for both lysines results in a loss of
transcriptionally active complex formation without affecting direct contact of
IkappaBzeta with p50. Both termini of the ANK domain in Bcl-3 and IkappaBNS
function in a manner similar to that of IkappaBzeta to interact with promoter
DNA, indicating a common mechanism in which the nuclear IkappaBs form a
regulatory complex with NF-kappaB and promoter DNA via the invariant aspartate in
ANK1 and the conserved basic residues in ANK7.
PMID- 27489105
TI - NADPH Oxidases Are Essential for Macrophage Differentiation.
AB - NADPH oxidases (NOXs) are involved in inflammation, angiogenesis, tumor growth,
and osteoclast differentiation. However, the role of NOX1 and NOX2 in macrophage
differentiation and tumor progression is still elusive. Here we report that NOX1
and NOX2 are critical for the differentiation of monocytes to macrophages, the
polarization of M2-type but not M1-type macrophages, and the occurrence of tumor
associated macrophages (TAMs). We found that deletion of both NOX1 and NOX2 led
to a dramatic decrease in ROS production in macrophages and resulted in impaired
efficiency in monocyte-to-macrophage differentiation and M2-type macrophage
polarization. We further showed that NOX1 and NOX2 were critical for the
activation of the MAPKs JNK and ERK during macrophage differentiation and that
the deficiency of JNK and ERK activation was responsible for the failure of
monocyte-to-macrophage differentiation, in turn affecting M2 macrophage
polarization. Furthermore, we demonstrated that the decrease in M2 macrophages
and TAMs, concomitant with the reduction of cytokine and chemokine secretion,
contributed to the delay in wound healing and the inhibition of tumor growth and
metastasis in NOX1/2 double knockout mice compared with WT mice. Collectively,
these data provide direct evidence that NOX1 and NOX2 deficiency impairs
macrophage differentiation and the occurrence of M2-type TAMs during tumor
development.
PMID- 27489106
TI - KHARON Is an Essential Cytoskeletal Protein Involved in the Trafficking of
Flagellar Membrane Proteins and Cell Division in African Trypanosomes.
AB - African trypanosomes and related kinetoplastid parasites selectively traffic
specific membrane proteins to the flagellar membrane, but the mechanisms for this
trafficking are poorly understood. We show here that KHARON, a protein originally
identified in Leishmania parasites, interacts with a putative trypanosome calcium
channel and is required for its targeting to the flagellar membrane. KHARON is
located at the base of the flagellar axoneme, where it likely mediates targeting
of flagellar membrane proteins, but is also on the subpellicular microtubules and
the mitotic spindle. Hence, KHARON is probably a multifunctional protein that
associates with several components of the trypanosome cytoskeleton. RNA
interference-mediated knockdown of KHARON mRNA results in failure of the calcium
channel to enter the flagellar membrane, detachment of the flagellum from the
cell body, and disruption of mitotic spindles. Furthermore, knockdown of KHARON
mRNA induces a lethal failure of cytokinesis in both bloodstream (mammalian host)
and procyclic (insect vector) life cycle stages, and KHARON is thus critical for
parasite viability.
PMID- 27489107
TI - Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1
(UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery.
AB - As a protein critical for DNA maintenance methylation and cell proliferation,
UHRF1 is frequently highly expressed in various human cancers and is considered
as a drug target for cancer therapy. In a high throughput screening for small
molecules that induce UHRF1 protein degradation, we have identified the HSP90
inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). We present evidence
that UHRF1 interacts with HSP90 chaperone complex and is a novel HSP90 client
protein. Pharmacological inhibition of HSP90 with 17-AAG or 17
dimethylaminoethylamino-17-demethoxygeldanamycin results in UHRF1 ubiquitination
and proteasome-dependent degradation. Interestingly, this HSP90 inhibitor-induced
UHRF1 degradation is independent of CHIP and CUL5, two previously identified
ubiquitin E3 ligases for HSP90 client proteins. In addition, this degradation is
dependent neither on the intrinsic E3 ligase of UHRF1 nor on the E3 ligase
SCF(beta-TRCP) that has been implicated in regulation of UHRF1 stability. We also
provide evidence that HSP90 inhibitors may suppress cancer cell proliferation in
part through its induced UHRF1 degradation. Taken together, our results identify
UHRF1 as a novel HSP90 client protein and shed light on the regulation of UHRF1
stability and function.
PMID- 27489108
TI - The Receptor Site and Mechanism of Action of Sodium Channel Blocker Insecticides.
AB - Sodium channels are excellent targets of both natural and synthetic insecticides
with high insect selectivity. Indoxacarb, its active metabolite DCJW, and
metaflumizone (MFZ) belong to a relatively new class of sodium channel blocker
insecticides (SCBIs) with a mode of action distinct from all other sodium channel
targeting insecticides, including pyrethroids. Electroneutral SCBIs preferably
bind to and trap sodium channels in the inactivated state, a mechanism similar to
that of cationic local anesthetics. Previous studies identified several SCBI
sensing residues that face the inner pore of sodium channels. However, the
receptor site of SCBIs, their atomic mechanisms, and the cause of selective
toxicity of MFZ remain elusive. Here, we have built a homology model of the open
state cockroach sodium channel BgNav1-1a. Our computations predicted that SCBIs
bind in the inner pore, interact with a sodium ion at the focus of P1 helices,
and extend their aromatic moiety into the III/IV domain interface (fenestration).
Using model-driven mutagenesis and electrophysiology, we identified five new SCBI
sensing residues, including insect-specific residues. Our study proposes the
first three-dimensional models of channel-bound SCBIs, sheds light on the
molecular basis of MFZ selective toxicity, and suggests that a sodium ion located
in the inner pore contributes to the receptor site for electroneutral SCBIs.
PMID- 27489109
TI - Chaperonin-containing T-complex Protein 1 Subunit zeta Serves as an Autoantigen
Recognized by Human Vdelta2 gammadelta T Cells in Autoimmune Diseases.
AB - Human gammadelta T cells recognize conserved endogenous and stress-induced
antigens typically associated with autoimmune diseases. However, the role of
gammadelta T cells in autoimmune diseases is not clear. Few autoimmune disease
related antigens recognized by T cell receptor (TCR) gammadelta have been
defined. In this study, we compared Vdelta2 TCR complementarity-determining
region 3 (CDR3) between systemic lupus erythematosus (SLE) patients and healthy
donors. Results show that CDR3 length distribution differed significantly and
displayed oligoclonal characteristics in SLE patients when compared with healthy
donors. We found no difference in the frequency of Jdelta gene fragment usage
between these two groups. According to the dominant CDR3delta sequences in SLE
patients, synthesized SL2 peptides specifically bound to human renal proximal
tubular epithelial cell line HK-2; SL2-Vm, a mutant V sequence of SL2, did not
bind. We identified the putative protein ligand chaperonin-containing T-complex
protein 1 subunit zeta (CCT6A) using SL2 as a probe in HK-2 cell protein extracts
by affinity chromatography and liquid chromatography-electrospray ionization
tandem mass spectrometry analysis. We found CCT6A expression on the surface of HK
2 cells. Cytotoxicity of only Vdelta2 gammadelta T cells to HK-2 cells was
blocked by anti-CCT6A antibody. Finally, we note that CCT6A concentration was
significantly increased in plasma of SLE and rheumatoid arthritis patients. These
data suggest that CCT6A is a novel autoantigen recognized by Vdelta2 gammadelta T
cells, which deepens our understanding of mechanisms in autoimmune diseases.
PMID- 27489111
TI - Characterization of the diffusive dynamics of particles with time-dependent
asymmetric microscopy intensity profiles.
AB - We put forth an algorithm to track isolated micron-size solid and liquid
particles that produce time-dependent asymmetric intensity patterns. This method
quantifies the displacement of a particle in the image plane from the peak of a
spatial cross-correlation function with a reference image. The peak sharpness
results in subpixel resolution. We demonstrate the utility of the method for
tracking liquid droplets with changing shapes and micron-size particles producing
images with exaggerated asymmetry. We compare the accuracy of diffusivity
determination with particles of known size by this method to that by common
tracking techniques and demonstrate that our algorithm is superior. We address
several open questions on the characterization of diffusive behaviors. We show
that for particles, diffusing with a root-mean-square displacement of 0.6 pixel
widths in the time between two successive recorded frames, more accurate
diffusivity determinations result from mean squared displacement (MSD) for lag
times up to 5 time intervals and that MSDs determined from non-overlapping
displacements do not yield more accurate diffusivities. We discuss the optimal
length of image sequences and demonstrate that lower frame rates do not affect
the accuracy of the estimated diffusivity.
PMID- 27489112
TI - Computational insight into the catalytic implication of head/tail-first
orientation of arachidonic acid in human 5-lipoxygenase: consequences for the
positional specificity of oxygenation.
AB - In the present work we have combined homology modeling, protein-ligand dockings,
quantum mechanics/molecular mechanics calculations and molecular dynamics
simulations to generate human 5-lipoxygenase (5-LOX):arachidonic acid (AA)
complexes consistent with the 5-lipoxygenating activity (which implies hydrogen
abstraction at the C7 position). Our results suggest that both the holo and the
apo forms of human Stable 5-LOX could accommodate AA in a productive form for 5
lipoxygenation. The former, in a tail-first orientation, with the AA carboxylate
end interacting with Lys409, gives the desired structures with C7 close to the Fe
OH(-) cofactor and suitable barrier heights for H7 abstraction. Only when using
the apo form structure, a head-first orientation with the AA carboxylate close to
His600 (a residue recently proposed as essential for AA positioning) is obtained
in the docking calculations. However, the calculated barrier heights for this
head-first orientation are in principle consistent with 5-LOX specificity, but
also with 12/8 regioselectivity. Finally, long MD simulations give support to the
recent hypothesis that the Phe177 + Tyr181 pair needs to close the active site
access during the chemical reaction, and suggest that in the case of a head-first
orientation Phe177 may be the residue interacting with the AA carboxylate.
PMID- 27489110
TI - Identification of NEK3 Kinase Threonine 165 as a Novel Regulatory Phosphorylation
Site That Modulates Focal Adhesion Remodeling Necessary for Breast Cancer Cell
Migration.
AB - Accumulating evidence supports a role for prolactin (PRL) in the development and
progression of human breast cancer. Although PRL is an established
chemoattractant for breast cancer cells, the precise molecular mechanisms of how
PRL regulates breast cancer cell motility and invasion are not fully understood.
PRL activates the serine/threonine kinase NEK3, which was reported to enhance
breast cancer cell migration, invasion, and the actin cytoskeletal reorganization
necessary for these processes. However, the specific mechanisms of NEK3
activation in response to PRL signaling have not been defined. In this report, a
novel PRL-inducible regulatory phosphorylation site within the activation segment
of NEK3, threonine 165 (Thr-165), was identified. Phosphorylation at NEK3 Thr-165
was found to be dependent on activation of the extracellular signal-regulated
kinase 1/2 (ERK1/2) signaling pathway using both pharmacological inhibition and
siRNA-mediated knockdown approaches. Strikingly, inhibition of phosphorylation at
NEK3 Thr-165 by expression of a phospho-deficient mutant (NEK3-T165V) resulted in
increased focal adhesion size, formation of zyxin-positive focal adhesions, and
reorganization of the actin cytoskeleton into stress fibers. Concordantly, NEK3
T165V cells exhibited migratory defects. Together, these data support a
modulatory role for phosphorylation at NEK3 Thr-165 in focal adhesion maturation
and/or turnover to promote breast cancer cell migration.
PMID- 27489113
TI - Variable Presentations of Lethal Colloid Cysts.
AB - Four cases of colloid cysts that led to death are reported to demonstrate their
nonspecific and protean presentations at autopsy: a 27-year-old man with severe
occipital headache, blurred vision, drowsiness and vomiting; a 44-year-old man
with recent memory disturbance; a 54-year-old man with head and neck pains,
tiredness, urinary incontinence, confusion, and drowsiness; and a 66-year-old man
with severe frontal headache, gait disturbance, vomiting, and syncope with a
previous episode of confusion and disorientation. Each death was due to an occult
colloid cyst obstructing the foramen of Monro causing acute hydrocephalus.
Nonspecific manifestations may mean that the diagnosis of colloid cyst is only
made at the time of autopsy. The possibility of rare cases being familial may
necessitate medical review of family members. Forensic evaluation should identify
how a colloid cyst was related to the mechanism of death and whether there are
any features that were associated with precipitate decline.
PMID- 27489114
TI - Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and
a binding site for the PP2Ac C-terminus.
AB - TOR signaling pathway regulator-like (TIPRL) is a regulatory protein which
inhibits the catalytic subunits of Type 2A phosphatases. Several cellular
contexts have been proposed for TIPRL, such as regulation of mTOR signaling,
inhibition of apoptosis and biogenesis and recycling of PP2A, however, the
underlying molecular mechanism is still poorly understood. We have solved the
crystal structure of human TIPRL at 2.15 A resolution. The structure is a novel
fold organized around a central core of antiparallel beta-sheet, showing an N
terminal alpha/beta region at one of its surfaces and a conserved cleft at the
opposite surface. Inside this cleft, we found a peptide derived from TEV-mediated
cleavage of the affinity tag. We show by mutagenesis, pulldown and
hydrogen/deuterium exchange mass spectrometry that this peptide is a mimic for
the conserved C-terminal tail of PP2A, an important region of the phosphatase
which regulates holoenzyme assembly, and TIPRL preferentially binds the
unmodified version of the PP2A-tail mimetic peptide DYFL compared to its tyrosine
phosphorylated version. A docking model of the TIPRL-PP2Ac complex suggests that
TIPRL blocks the phosphatase's active site, providing a structural framework for
the function of TIPRL in PP2A inhibition.
PMID- 27489115
TI - A prospective, multicentre, open-label, single-arm clinical trial for treatment
of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive
clinical outcomes of viable cryopreserved human placental membrane.
AB - Complex diabetic foot ulcers (DFUs) with exposed tendon or bone remain a
challenge. They are more susceptible to complications such as infection and
amputation and require treatments that promote rapid development of granulation
tissue and, ultimately, reepithelialisation. The clinical effectiveness of viable
cryopreserved human placental membrane (vCHPM) for DFUs has been established in a
level 1 trial. However, complex wounds with exposed deeper structures are
typically excluded from randomised controlled clinical trials despite being
common in clinical practice. We report the results of a prospective, multicentre,
open-label, single-arm clinical trial to establish clinical outcomes when vCHPM
is applied weekly to complex DFUs with exposed deep structures. Patients with
type 1 or type 2 diabetes and a complex DFU extending through the dermis with
evidence of exposed muscle, tendon, fascia, bone and/or joint capsule were
eligible for inclusion. Of the 31 patients enrolled, 27 completed the study. The
mean wound area was 14.6 cm2 , and mean duration was 7.5 months. For patients
completing the protocol, the primary endpoint, 100% wound granulation by week 16,
was met by 96.3% of patients in a mean of 6.8 weeks. Complete wound closure
occurred in 59.3% (mean 9.1 weeks). The 4-week percent area reduction was 54.3%.
There were no product-related adverse events. Four patients (13%) withdrew, two
(6.5%) for non-compliance and two (6.5%) for surgical intervention.
PMID- 27489116
TI - Is there an obesity paradox in the Japanese elderly population? A community-based
cohort study of 13 280 men and women.
AB - AIM: Despite increased interest in an obesity paradox (i.e. a survival advantage
of being obese), evidence remains sparse in Japanese populations. We aimed to
verify this phenomenon among community-dwelling older adults in Japan. METHODS:
Older adults aged 65-84 years randomly chosen from all 74 municipalities in
Shizuoka Prefecture completed questionnaires including body mass index
information. Participants were followed from 1999 to 2009. Following World Health
Organization guidelines, participants were classified using an appropriate body
mass index for Asian populations as follows: <18.5 kg/m2 (underweight), 18.5-23.0
kg/m2 (normal weight), 23.0-27.5 kg/m2 (overweight) and >=27.5 kg/m2 (obesity).
We estimated hazard ratios and their 95% confidence intervals for all-cause
mortality, controlling for sex, age, smoking status, alcohol consumption,
physical activity, hypertension and diabetes mellitus. RESULTS: Compared with
normal-weight participants, overweight/obese participants tended to have lower
hazard ratios; the multivariate hazard ratios (95% confidence interval) were 0.86
(0.62-1.19) for obesity, 0.83 (0.73-0.94) for overweight and 1.60 (1.40-1.82) for
underweight. In subgroup analyses by sex and age, the hazard ratios tended to be
lower among obese men, albeit not significantly; hazard ratios (95% confidence
interval) were 0.56 (0.25-1.27) in men aged 65-74 years, and 0.78 (0.41-1.45) in
men aged 75-84 years. CONCLUSIONS: The present study provides evidence of a
conservative obesity paradox among older Japanese people, using the appropriate
body mass index cut-off points for Asian populations. In particular, obese older
men tend to have a lower risk of all-cause mortality. Geriatr Gerontol Int 2017;
17: 1257-1264.
PMID- 27489117
TI - Cohesin complex is a major player on the stage of leukemogenesis.
PMID- 27489118
TI - Diagnostic accuracy of procalcitonin and presepsin for infectious disease in
patients with acute kidney injury.
AB - Procalcitonin (PCT) and presepsin (PSEP) are sepsis markers, but their diagnostic
accuracy may be compromised in acute kidney injury (AKI). We evaluated their
diagnostic accuracy in patients with/without AKI. This retrospective study
comprised 91 patients with at least one criterion of systematic inflammatory
response syndrome. AKI markers plasma neutrophil gelatinase-associated lipocalin
(NGAL), plasma cystatin C (CysC), and estimated glomerular filtration rate (eGFR)
were measured upon hospital admission and on days 1, 3, 5, and 7. Patients were
divided into non-AKI and AKI groups. APACHE II severity scores were determined.
PCT and PSEP levels were increased significantly in non-AKI and AKI patients with
infection. NGAL, CysC, and eGFR in patients with infection were associated with
PCT, PSEP, and APACHE II score, and levels of PCT and PSEP were correlated
significantly with disease severity. PCT and PSEP are useful markers of bacterial
infections in AKI but different thresholds should be applied.
PMID- 27489119
TI - Recovery of Neisseria gonorrhoeae from 4 commercially available transport
systems.
AB - Four commercial transport systems for the recovery of Neisseria gonorrhoeae were
evaluated in support of the need to obtain culture isolates for the detection of
antimicrobial resistance. Bacterial recovery from the InTray GC system was
superior with minimal loss of viability in contrast to non-nutritive transport
systems.
PMID- 27489120
TI - Oxidative Stress Is Involved in the Renal Dysfunction Induced by Sinoaortic
Denervation in Rats.
AB - The hypothesis that oxidative stress contributes to renal dysfunction in
sinoaortically denervated (SAD) rats was investigated. Rats were sinoaortically
denervated and received treatment with tempol (0.5 mmol/L in drinking water) for
8 weeks. Although the tempol treatment of the SAD rats had no significant effect
on blood pressure or blood pressure viability, it significantly ameliorated the
renal dysfunction as indicated by increases in renal blood flow (RBF) and the
glomerular filtration rate (GFR) and reductions in plasma creatinine, blood urea
nitrogen (BUN), the urine albumin excretion rate (UAE), and the glomerular
sclerosis score (GSS). The SAD rats treated with tempol exhibited decreased
plasma and renal malondialdehyde (MDA) levels and reduced renal formation of
reactive oxygen species (ROS), superoxide (O2-), peroxynitrite (OONO-) and 3
nitrotyrosine. Treatment with tempol suppressed the nuclear concentration of
nuclear factor-kappaB (NF-kappaB) and reduced the renal levels of macrophage
chemoattractant protein 1 (MCP-1) and interleukin-6 (IL-6). The tempol-treated
SAD rats exhibited decreased renal advanced glycation end product (AGE) levels
and decreased receptor for advanced glycation end products (RAGE) protein
expression. The tempol treatment of the SAD rats restored mitochondrial adenosine
triphosphate (ATP) formation, DNA content, membrane integrity and the renal
oxygen consumption rate. Additionally, the activities of superoxide dismutase
(SOD), glutathione peroxidase (GPx), glutathione S epoxide transferase (GST), and
catalase were decreased, and the activities of xanthin oxidase (XO) and reduced
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were enhanced in the
kidneys of the SAD rats. In conclusion, our work firstly provided direct evidence
that oxidative stress played an important role in the renal dysfunction of SAD
rats.
PMID- 27489121
TI - Visual-cognitive tools used to determine fitness-to-drive may reflect normal
aging.
AB - BACKGROUND: Scores on many visual-cognitive tools are proposed as indicators of
fitness-to-drive. A purported feature of some tools and one believed to be
important is that they are 'age-independent'. Specifically, scores are not
correlated with age and poor scores represent a pathological process rather than
normal aging. Yet, we know that several cognitive abilities are associated with
age. One potential reason for the apparent age-independence of some tools is that
focusing on older drivers leads to 'range restriction', a statistical issue that
reduces the magnitude of correlations when values for one variable are restricted
to a smaller range than naturally occurs. Hence, the purpose of this study was to
investigate whether age is correlated with scores on visual-cognitive tests when
we examine the full age range. METHODS: We recruited 114 drivers aged 18 to 89
years (mean: 42.30 +/- 26.50 years). Participants completed several visual
cognitive tools often used to examine fitness-to-drive (Trail Making Tests A and
B, Attention Network Test and 'useful field of view'). RESULTS: Correlations
between age and test scores for drivers 65 years and older only ranged from 0.03
to 0.48. With the whole age range, correlations ranged from 0.56 to 0.84. We also
compared ordinary Pearson correlations among visual-cognitive tests scores to the
corresponding partial correlations after removing the effect of age. Whereas
ordinary Pearson correlations ranged from 0.40 to 0.69, partial correlations
ranged from 0.01 to 0.30. CONCLUSION: Test scores may reflect age-associated
normal biological changes. These results have implications for predicting fitness
to-drive among older drivers and suggest caution in using these scores.
PMID- 27489123
TI - Lead Angle Matters: Side Effects of Deep Brain Stimulation Improved With
Adjustment of Lead Angle.
AB - BACKGROUND: Targeting the subthalamic nucleus (STN) for deep brain stimulation
(DBS) using standard stereotactic coordinates in conjunction with high-resolution
magnetic resonance imaging (MRI) generally results in effective symptomatic
relief for the cardinal motor features of Parkinson's disease (PD). The angle of
approach, however, influences the resultant field of stimulation and can lead to
undesired side effects. METHODS: We review a case where symptomatic improvement
was accompanied by significant side effects despite reasonable STN stereotactic
base coordinates. Revision of the lead using similar base coordinates but a
significantly different angle of approach greatly improved the outcome. RESULTS:
Stimulation ventromedial to the STN improved tremors but brought about dysarthria
and dystonia. Computer-based stimulation field modeling helped understand the
regions associated with the side effects and illustrate the difference between
pre- and post-revision stimulation fields. CONCLUSION: Lead angle can impact DBS
outcome and should be taken into consideration.
PMID- 27489122
TI - Downregulation of the long noncoding RNA GAS5-AS1 contributes to tumor metastasis
in non-small cell lung cancer.
AB - Long noncoding RNA (lncRNA) plays pivotal roles in cancer development. To date,
only a small number of lncRNAs have been characterized at functional level. Here,
we discovered a novel lncRNA termed GAS5-AS1 as a tumor suppressor in non-small
cell lung cancer (NSCLC). The expression of GAS5-AS1 in NSCLC tumors was much
lower than that in the adjacent normal lung tissues. The reduced GAS5-AS1 was
significantly correlated with larger tumors, higher TNM stages, and lymph node
metastasis in NSCLC patients. While ectopic expression or specific knockdown of
GAS5-AS1 had no effect on proliferation, cell cycle progression, and apoptosis,
it dramatically decreased or increased, respectively, NSCLC cell migration and
invasion. Overexpression of GAS5-AS1 in NSCLC cells reduced a cohort of molecules
(ZEB1, N-cadherin, Vimentin, and/or Snail1) critical for epithelial-mesenchymal
transition (EMT). Furthermore, the DNA demethylating agent 5-aza-2-deoxycytidine
failed to upregulate GAS5-AS1 in NSCLC cells, whereas the pan-HDAC inhibitors
panobinostat and SAHA significantly induced GAS5-AS1 in a dose-dependent manner.
In addition, GAS5-AS1 can be upregulated by specific knockdown of HDAC1 or HDAC3.
Collectively, our data suggest that histone modifications play a major role
leading to epigenetic silencing of GAS5-AS1 in NSCLC and subsequently promote
tumor metastasis via upregulation of several key EMT markers.
PMID- 27489124
TI - Goodbye BRONJ... Hello MRONJ.
PMID- 27489125
TI - Discriminating in favour of or against men with increased risk of finasteride
related side effects?
PMID- 27489126
TI - Blood film findings in anaplasmosis.
PMID- 27489127
TI - Insight into In Situ Amphiphilic Functionalization of Few-Layered Transition
Metal Dichalcogenide Nanosheets.
AB - A facile route toward functionalized amphiphilic layered transition-metal
dichalcogenide nanosheets through in situ polymerization of polystyrene
polyacrylamide copolymers is established. The attachment of copolymers greatly
affects their dispersibility in different kinds of solvents. Surface-tension
components, polarity, and coordination effects of the copolymer are found to be
the main factors affecting the dispersibility.
PMID- 27489128
TI - Experimental Identification of Electric Field Excitation Mechanisms in a
Structural Transition of Tokamak Plasmas.
AB - Self-regulation between structure and turbulence, which is a fundamental process
in the complex system, has been widely regarded as one of the central issues in
modern physics. A typical example of that in magnetically confined plasmas is the
Low confinement mode to High confinement mode (L-H) transition, which is
intensely studied for more than thirty years since it provides a confinement
improvement necessary for the realization of the fusion reactor. An essential
issue in the L-H transition physics is the mechanism of the abrupt "radial"
electric field generation in toroidal plasmas. To date, several models for the L
H transition have been proposed but the systematic experimental validation is
still challenging. Here we report the systematic and quantitative model
validations of the radial electric field excitation mechanism for the first time,
using a data set of the turbulence and the radial electric field having a high
spatiotemporal resolution. Examining time derivative of Poisson's equation, the
sum of the loss-cone loss current and the neoclassical bulk viscosity current is
found to behave as the experimentally observed radial current that excites the
radial electric field within a few factors of magnitude.
PMID- 27489129
TI - Synthesis and characterization of insulin/zirconium phosphate@TiO2 hybrid
composites for enhanced oral insulin delivery applications.
AB - In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP)
were synthesized by intercalation method, then, these composites were coated with
TiO2 by sol-gel method to prepare Ins/ZrP@TiO2 hybrid composites and the drug
release of the composites was investigated by using UV-Vis spectroscopy. Ins/ZrP
(10, 30, 60 wt%) composites were prepared by intercalation of insulin into the
ZrP layers in water. Then Ins/ZrP composites were coated with different amounts
of TiO2 (30, 50, 100 wt %) by using titanium tetra n-butoxide, as precursor.
Formation of intercalated Ins/ZrP and Ins/ZrP@TiO2 hybrid composites was
characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the
optimized Ins/ZrP@TiO2 hybrid composite was determined -27.2 mV. Cytotoxic
effects of the optimized Ins/ZrP@TiO2 hybrid composite against HeLa and Hek293T
cell lines were evaluated using MTT assay and the results showed that designed
drug delivery system was not toxic in biological environment. Compared to the
Ins/ZrP composites, incorporation of TiO2 coating enhanced the drug entrapment
considerably, and reduced the drug release. The Ins/ZrP composites without TiO2
coating released the whole drug after 30 min in pH 7.4 (phosphate buffer
solution) while the TiO2-coated composites released the entrapped drug after 20
h. In addition to increasing the shelf life of hormone, this nanoencapsulation
and nanocoating method can convert the insulin utilization from injection to oral
and present a painless and more comfortable treatment for diabetics.
PMID- 27489130
TI - Corrigendum: Observation of a topological crystalline insulator phase and
topological phase transition in Pb1-xSnxTe.
PMID- 27489131
TI - Maltaricin CPN, a new class IIa bacteriocin produced by Carnobacterium
maltaromaticum CPN isolated from mould-ripened cheese.
AB - AIMS: The purpose of this study was to isolate, characterize and determine the
structure and the antibacterial activities of a bacteriocin produced by
Carnobacterium maltaromaticum CPN, a strain isolated from unpasteurized milk
Camembert cheese. METHODS AND RESULTS: This bacteriocin, termed maltaricin CPN,
was produced at higher amounts in MRS broth at temperatures between 15 degrees C
and 25 degrees C. It was purified to homogeneity from culture supernatant by
using a simple method consisting of cation-exchange and reversed-phase
chromatographies. Mass spectrometry showed that maltaricin was a 4427.29 Da
bacteriocin. Its amino acid sequence was determined by Edman degradation which
showed that it had close similarity with bacteriocins of the class IIa.
Maltaricin CPN consisted in fact of 44 unmodified amino acids including two
cysteine residues at positions 9 and 14 linked by a disulphide bond. The
antimicrobial activity of maltaricin CPN covered a range of bacteria, with strong
activity against many species of Gram-positive bacteria, especially the food
borne pathogen Listeria monocytogenes, but no activity against Gram-negative
ones. CONCLUSIONS: In the studied conditions, C. maltaromaticum CPN produced a
new class IIa bacteriocin with strong anti-Listeria activity. SIGNIFICANCE AND
IMPACT OF THE STUDY: The study covers the purification and the structural
characterization of a new bacteriocin produced by strain C. maltaromaticum CPN
isolated from Camembert cheese. Its activity against strains of L. monocytogenes
and higher production rates at relatively low temperatures show potential
technological applications to improve the safety of refrigerated food.
PMID- 27489132
TI - Organocatalyzed Novel Synthetic Methodology for Highly Functionalized Piperidines
as Potent alpha-Glucosidase Inhibitors.
AB - An efficient atom-economic one-pot synthesis of highly functionalized piperidines
was achieved by catalytic multicomponent reaction. A wide range of heterogeneous
and homogenous catalysts were explored; however, promising results were achieved
when a beta-keto-ester was reacted with selected aromatic aldehydes and anilines
by using N-acetyl glycine (NAG) as catalyst. The implication of this methodology
is straightforward since the products were precipitated out from the reaction
solution, eliminating the need of column chromatography purifications. The
synthesized piperidines were screened against alpha-glucosidase inhibition, which
revealed that these compounds were very active inhibitors, and some of the
compounds showed even better inhibition than the reference compound, at low
micromolar concentrations. In silico molecular modeling was also performed to
investigate the binding modes of the compounds into the active sites of the
target protein.
PMID- 27489133
TI - The protective effect of resveratrol against cytotoxicity induced by mycotoxin,
zearalenone.
AB - Zearalenone (ZEA), a non-steroidal estrogenic mycotoxin, is widely present in
cereals and agricultural products. The literature reports suggest that oxidative
damage seems to be a key determinant of ZEA-induced toxicity, and the protective
effect of resveratrol (RSV), an antioxidant phenolic compound, on ZEA-induced
cytotoxicity to HEK293 cells was investigated. The experimental results showed
that ZEA decreased cell viability in a dose dependent manner with an IC50 value
of 80 MUM, and induced an increase in intracellular reactive oxygen species (ROS)
in HEK293 cells. A remarkable elevation of MDA and decreased activity of
manganese superoxide dismutase (MnSOD) were also observed. A decrease in
mitochondrial membrane potential (MMP), cell cycle arrest at the G0/G1 phase, and
increased cell apoptosis indicate a mitochondria-mediated apoptosis. RSV (2 MUM)
pretreatment not only recovered the activity of MnSOD, but also improved ZEA
induced cytotoxicity evidenced by increased MMP and cell viability, and decreased
ROS. Furthermore, RSV pretreatment substantially upregulated the expression of
the SIRT1 gene by 6.8 fold, reduced the acetylation level of the forkhead
transcription factor FOXO3a, and decreased the expression ratio of Bax/Bcl-2. All
these results demonstrated that RSV exhibited significant protective effects on
ZEA-induced cell damage, and this effect may be attributed to the upregulation of
SIRT1 and activation of FOXO3a-mediated pathways to enhance the resistance of
cells to oxidative stress induced by ZEA exposure.
PMID- 27489134
TI - Long-Term Results After Single and Multiple Procedures of Ablation of Ventricular
Tachycardia.
AB - INTRODUCTION: The aim of this study was to assess long-term results after single
and multiple procedures of catheter ablation of ventricular tachycardia (VT).
While it is generally accepted that multiple procedures are sometimes necessary
in order to achieve long-term clinical success, the literature on this issue
displays wide variability. METHODS: We assessed the outcome of 160 consecutive
patients who underwent 214 ablation procedures in the period 2008 to May 2015: 93
had overt structural heart disease (SHD) (previous myocardial infarction in 74
cases) and 67 had no SHD. RESULTS: After the first procedure, the 1-year
actuarial recurrence rates were 25% in patients with SHD and 5% in those without.
However, recurrences increased progressively after the first year, reaching 46%
and 35%, respectively, at 5 years. Overall, VT recurred in 35/93 (38%) patients
with SHD and 22/67 (33%) patients without. Redo (1 to 4) procedures were
performed in 28 (20%) patients with SHD and 18 (27%) patients without. After the
last procedure, the 1-year actuarial recurrence rates were 5% in patients with
SHD and 7% in those without, and the corresponding rates at 5 years were 23% and
7%. During follow-up, 21 patients died (all in the SHD group): no death was
related to VT recurrence. CONCLUSIONS: During long-term follow-up, VT frequently
recurs after the first procedure, both in patients with SHD and in those without;
multiple procedures are needed in order to increase the success rate.
PMID- 27489135
TI - Characterization and Evaluation of a Salmonella enterica Serotype Senftenberg
Mutant Created by Deletion of Virulence-Related Genes for Use as a Live
Attenuated Vaccine.
AB - Natural infections of chickens with Salmonella enterica subsp. enterica serovar
Senftenberg (S. Senftenberg) are characterized by low-level intestinal
invasiveness and insignificant production of antibodies. In this study, we
investigated the potential effects of lon and cpxR gene deletions on the
invasiveness of S Senftenberg into the intestinal epithelium of chickens and its
ability to induce an immune response, conferring protection against S Senftenberg
infection. With the allelic exchange method, we developed JOL1596 (Deltalon),
JOL1571 (DeltacpxR), and JOL1587 (Deltalon DeltacpxR) deletion mutants from wild
type S Senftenberg. Deletion of the lon gene from S Senftenberg produced
increased frequency of elongated cells, with significantly greater amounts of
exopolysaccharide (EPS) than in the cpxR-deleted strain and the wild-type strain.
The in vivo intestinal loop invasion assay showed a significant increase in
epithelial invasiveness for JOL1596 (Deltalon) and JOL1587 (Deltalon DeltacpxR),
compared to JOL1571 (DeltacpxR) and the wild-type strain. Furthermore, the S
Senftenberg wild-type and mutant strains were internalized at high levels inside
activated abdominal macrophages from chicken. The in vivo inoculation of JOL1587
(Deltalon DeltacpxR) into chickens led to colonization of the liver, spleen, and
cecum for a short time. Chickens inoculated with JOL1587 (Deltalon DeltacpxR)
showed significant increases in humoral, mucosal, and cellular immune responses
specific to S Senftenberg antigens. Postchallenge, compared to the control group,
the JOL1587 (Deltalon DeltacpxR)-inoculated chickens showed not only lower
persistence but also faster clearance of wild-type S Senftenberg from the cecum.
We conclude that the increased intestinal invasiveness and colonization of
internal organs exhibited by JOL1587 (Deltalon DeltacpxR) led to the
establishment of immunogenicity and conferred protective efficacy against S
Senftenberg infections in chickens.
PMID- 27489137
TI - Angular default mode network connectivity across working memory load.
AB - Initially identified during no-task, baseline conditions, it has now been
suggested that the default mode network (DMN) engages during a variety of working
memory paradigms through its flexible interactions with other large-scale brain
networks. Nevertheless, its contribution to whole-brain connectivity dynamics
across increasing working memory load has not been explicitly assessed. The aim
of our study was to determine which DMN hubs relate to working memory task
performance during an fMRI-based n-back paradigm with parametric increases in
difficulty. Using a voxel-wise metric, termed the intrinsic connectivity contrast
(ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the
greatest change in global connectivity across three levels of n-back task load.
Subsequent seed-based functional connectivity analysis revealed that the angular
DMN regions robustly interact with other large-scale brain networks, suggesting a
potential involvement in the global integration of information. Further support
for this hypothesis comes from the significant correlations we found between
angular gyri connectivity and reaction times to correct responses. The
implication from our study is that the DMN is actively involved during the n-back
task and thus plays an important role related to working memory, with its core
angular regions contributing to the changes in global brain connectivity in
response to increasing environmental demands. Hum Brain Mapp 38:41-52, 2017. (c)
2016 Wiley Periodicals, Inc.
PMID- 27489136
TI - Multifunctional T Cell Response to DosR and Rpf Antigens Is Associated with
Protection in Long-Term Mycobacterium tuberculosis-Infected Individuals in
Colombia.
AB - Multifunctional T cells have been shown to be protective in chronic viral
infections. In mycobacterial infections, however, evidence for a protective role
of multifunctional T cells remains inconclusive. Short-term cultures of
peripheral blood mononuclear cells stimulated with the Mycobacterium tuberculosis
RD1 antigens 6-kDa early secretory antigenic target (ESAT6) and 10-kDa culture
filtrate antigen (CFP10), which are induced in the early infection phase, have
been mainly used to assess T cell multifunctionality, although long-term culture
assays have been proposed to be more sensitive than short-term assays for
assessment of memory T cells, which are essential for long-term immunity. Here we
used a long-term culture assay system to study the T cell immune responses to the
M. tuberculosis latency-associated DosR antigens and reactivation-associated Rpf
antigens, compared to ESAT6 and CFP10, in patients with pulmonary tuberculosis
(PTB) and household contacts of PTB patients with long-term latent tuberculosis
infection (ltLTBI), in a community in which M. tuberculosis is endemic. Our
results showed that the DosR antigens Rv1737c (narK2) and Rv2029c (pfkB) and the
Rv2389c (rpfD) antigen of M. tuberculosis induced higher frequencies of CD4+ or
CD8+ mono- or bifunctional (but not multifunctional) T cells producing interferon
gamma (IFN-gamma) and/or tumor necrosis alpha (TNF-alpha) in ltLTBI, compared to
PTB. Moreover, the frequencies of CD4+ and/or CD8+ T cells with a CD45RO+ CD27+
phenotype were higher in ltLTBI than in PTB. Thus, the immune responses to
selected DosR and Rpf antigens may be associated with long-term latency,
correlating with protection from M. tuberculosis reactivation in ltLTBI. Further
study of the functional and memory phenotypes may contribute to further
discrimination between the different states of M. tuberculosis infections.
PMID- 27489138
TI - Highly stable tandem solar cell monolithically integrating dye-sensitized and
CIGS solar cells.
AB - A highly stable monolithic tandem solar cell was developed by combining the
heterogeneous photovoltaic technologies of dye-sensitized solar cell (DSSC) and
solution-processed CuInxGa1-xSeyS1-y (CIGS) thin film solar cells. The durability
of the tandem cell was dramatically enhanced by replacing the redox couple from
to [Co(bpy)3](2+) /[Co(bpy)3](3+)), accompanied by a well-matched counter
electrode ( PEDOT: PSS) and sensitizer (Y123). A 1000 h durability test of the
DSSC/CIGS tandem solar cell in ambient conditions resulted in only a 5% decrease
in solar cell efficiency. Based on electrochemical impedance spectroscopy and
photoelectrochemical cell measurement, the enhanced stability of the tandem cell
is attributed to minimal corrosion by the cobalt-based polypyridine complex redox
couple.
PMID- 27489139
TI - Distinctive microRNA expression in early stage nasopharyngeal carcinoma patients.
AB - The goal of this study was to investigate microRNAs (miRs) expression at
different stages of nasopharyngeal carcinoma (NPC). MiR expression profiling at
various stages of NPC was performed by miR array and further verified using
quantitative real-time RT-PCR. Pathway enrichment analysis was carried out to
identify the functional pathways regulated by the miRs. The expression of a
selected group of identified miRs was verified in stage I NPC by in situ
hybridization (ISH). A total of 449 miRs were identified with significantly
different expressions between NPC tissues and normal pharyngeal tissues. Eighty
four miRs were dysregulated only in stage I NPC, among which 45 miRs were up
regulated and the other 39 were down-regulated. Pathway enrichment assay revleaed
that three significantly down-regulated and three significantly up-regulated miRs
involved in 12 pathways associating with tumour formation and progression.
Quantitative RT-PCR confirmed the miR array result. In addition, the low
expression levels of hsa-miR-4324, hsa-miR-203a and hsa-miR-199b-5p were further
validated in stage I NPC by ISH. This present study identifed the miR signature
in stage I NPC, providing the basis for early detection and treatment of NPC.
PMID- 27489140
TI - Prostate cancer outcomes for men who present with symptoms at diagnosis.
AB - OBJECTIVE: To compare clinical features, treatments and outcomes in men with non
metastatic prostate cancer (PCa) according to whether they were referred for
symptoms or elevated prostate-specific antigen (PSA) level. PATIENTS AND METHODS:
This study used data from the South Australia Prostate Cancer Clinical Outcomes
Collaborative database; a multi-institutional clinical registry covering both the
public and private sectors. We included all non-metastatic cases from 1998 to
2013 referred for urinary/prostatic symptoms or elevated PSA level. Multivariate
Poisson regression was used to identify characteristics associated with
symptomatic presentation and compare treatments according to reason for referral.
Outcomes (i.e. overall survival, PCa-specific survival, metastasis-free survival
and disease-free survival) were compared using multivariate Cox proportional
hazards and competing risk regression. RESULTS: Our analytical cohort consisted
of 4 841 men with localized PCa. Symptomatic men had lower-risk disease
(incidence ratio [IR] 0.70, 95% confidence interval [CI] 0.61-0.81 for high vs
low risk), fewer radical prostatectomies (IR 0.64, CI: 0.56-0.75) and less
radiotherapy (IR 0.86, CI: 0.77-0.96) than men presenting with elevated PSA
level. All-cause mortality (hazard ratio [HR] 1.31, CI: 1.16-1.47), disease
specific mortality (HR 1.42, CI: 1.13-1.77) and risk of metastases (HR 1.36, CI:
1.13-1.64) were higher for men presenting with symptoms, after adjustment for
other clinical characteristics; however, risk of disease progression did not
differ (HR 0.90, CI: 0.74-1.07) amongst those treated curatively. Subgroup
analyses indicated poorer PCa survival for symptomatic referral among men
undergoing radical prostatectomy (HR 3.4, CI: 1.3-8.8), those aged >70 years (HR
1.4, CI: 1.0-1.8), men receiving private treatment (HR 2.1, CI: 1.3-3.3), those
diagnosed via biopsy (HR 1.3, CI: 1.0-1.7) and those diagnosed before 2006 (HR
1.6, CI: 1.2-2.7). CONCLUSION: Our results suggest that symptomatic presentation
may be an independent negative prognostic indicator for PCa survival. More
complete assessment of disease grade and extent, more definitive treatment and
increased post-treatment monitoring among symptomatic cases may improve outcomes.
Further research to determine any pathophysiological basis for poor outcomes in
symptomatic men is warranted.
PMID- 27489141
TI - Aqueous fruit extract of Mimusops elengi causes reversible suppression of
spermatogenesis and fertility in male mice.
AB - Antifertility efficacy of oral administration of aqueous fruit extract of
Mimusops elengi (200, 400 and 600 mg kg(-1) body weight/day for 35 days) was
evaluated in Parkes strain male mice. Various reproductive end points such as
histopathology, sperm parameters, testosterone level, haematology, serum
biochemistry and fertility indices were assessed; activities of 3beta- and 17beta
hydroxysteroid dehydrogenases, and immunoblot expressions of StAR and P450scc in
the testis were also assessed. Histologically, testes in Mimusops-treated mice
showed nonuniform and diverse degenerative changes in the seminiferous tubules;
both affected and normal tubules were observed in the same sections of testis.
The treatment had adverse effects on testicular hydroxysteroid dehydrogenases and
StAR and P450scc, serum level of testosterone and on motility, viability and
number of spermatozoa in cauda epididymis. However, serum levels of alanine
aminotransferase, aspartate aminotransferase and creatinine, and haematological
parameters were not affected by the treatment. Also, libido was not affected in
treated males, but their fertility was markedly suppressed. By 56 days of
treatment withdrawal, the alterations caused in the above parameters recovered to
control levels, suggesting that Mimusops treatment causes reversible suppression
of spermatogenesis and fertility in Parkes mice. Further, there were no
detectable signs of toxicity in treated males.
PMID- 27489142
TI - Assessment of 3 Bowel Preparation Protocols for Computed Tomography
Pneumocolonography in Normal Dogs.
AB - OBJECTIVE: To investigate the effects of 3 different bowel preparation protocols
on interpretation of computed tomography (CT) pneumocolonography images. STUDY
DESIGN: Experimental crossover design. ANIMALS: Intact male, hound-cross,
research colony dogs (n=4). METHODS: All dogs received the 3 different bowel
preparation protocols for CT pneumocolonography in the same order, with a minimum
of 2 weeks between protocols. For each segment of large bowel, the subjective
adequacy of bowel cleansing was assessed, residual fecal and bowel volumes were
calculated, and the density of fecal material in the bowel lumen was measured.
Linear mixed effect models that included a random dog effect were used to
evaluate mean differences in outcome measures across protocols. RESULTS: No dogs
experienced any clinical problems associated with the protocols or CT
pneumocolonography. Bowel cleansing was considered adequate for CT
pneumocolonography interpretation for all 3 protocols. There was a significant
effect of protocol on residual fecal volumes and the fecal:bowel volume ratio,
with the 2 protocols that included an extended fast producing the lowest total
residual fecal volumes. There was a significant effect of protocol on maximum
measured density of residual fecal material with the 2 protocols including
iodinated contrast having the highest density. CONCLUSIONS: All protocols were
sufficient for CT pneumocolonography interpretation and contrast-tagging of
residual fecal material was successful with oral iopamidol administration. An at
home bowel cleansing protocol may provide adequate bowel cleansing for CT
pneumocolonography image interpretation.
PMID- 27489143
TI - Integrating Evidence From Systematic Reviews, Qualitative Research, and Expert
Knowledge Using Co-Design Techniques to Develop a Web-Based Intervention for
People in the Retirement Transition.
AB - BACKGROUND: Integrating stakeholder involvement in complex health intervention
design maximizes acceptability and potential effectiveness. However, there is
little methodological guidance about how to integrate evidence systematically
from various sources in this process. Scientific evidence derived from different
approaches can be difficult to integrate and the problem is compounded when
attempting to include diverse, subjective input from stakeholders. OBJECTIVE: The
intent of the study was to describe and appraise a systematic, sequential
approach to integrate scientific evidence, expert knowledge and experience, and
stakeholder involvement in the co-design and development of a complex health
intervention. The development of a Web-based lifestyle intervention for people in
retirement is used as an example. METHODS: Evidence from three systematic
reviews, qualitative research findings, and expert knowledge was compiled to
produce evidence statements (stage 1). Face validity of these statements was
assessed by key stakeholders in a co-design workshop resulting in a set of
intervention principles (stage 2). These principles were assessed for face
validity in a second workshop, resulting in core intervention concepts and hand
drawn prototypes (stage 3). The outputs from stages 1-3 were translated into a
design brief and specification (stage 4), which guided the building of a
functioning prototype, Web-based intervention (stage 5). This prototype was de
risked resulting in an optimized functioning prototype (stage 6), which was
subject to iterative testing and optimization (stage 7), prior to formal pilot
evaluation. RESULTS: The evidence statements (stage 1) highlighted the
effectiveness of physical activity, dietary and social role interventions in
retirement; the idiosyncratic nature of retirement and well-being; the value of
using specific behavior change techniques including those derived from the Health
Action Process Approach; and the need for signposting to local resources. The
intervention principles (stage 2) included the need to facilitate self-reflection
on available resources, personalization, and promotion of links between key
lifestyle behaviors. The core concepts and hand-drawn prototypes (stage 3) had
embedded in them the importance of time use and work exit planning, personalized
goal setting, and acceptance of a Web-based intervention. The design brief
detailed the features and modules required (stage 4), guiding the development of
wireframes, module content and functionality, virtual mentors, and intervention
branding (stage 5). Following an iterative process of intervention testing and
optimization (stage 6), the final Web-based intervention prototype of LEAP
(Living, Eating, Activity, and Planning in retirement) was produced (stage 7).
The approach was resource intensive and required a multidisciplinary team. The
design expert made an invaluable contribution throughout the process.
CONCLUSIONS: Our sequential approach fills an important methodological gap in the
literature, describing the stages and techniques useful in developing an evidence
based complex health intervention. The systematic and rigorous integration of
scientific evidence, expert knowledge and experience, and stakeholder input has
resulted in an intervention likely to be acceptable and feasible.
PMID- 27489145
TI - Massive central nervous system infiltration by CD56-positive plasma cells in
multiple myeloma.
PMID- 27489144
TI - Intrinsic limits to gene regulation by global crosstalk.
AB - Gene regulation relies on the specificity of transcription factor (TF)-DNA
interactions. Limited specificity may lead to crosstalk: a regulatory state in
which a gene is either incorrectly activated due to noncognate TF-DNA
interactions or remains erroneously inactive. As each TF can have numerous
interactions with noncognate cis-regulatory elements, crosstalk is inherently a
global problem, yet has previously not been studied as such. We construct a
theoretical framework to analyse the effects of global crosstalk on gene
regulation. We find that crosstalk presents a significant challenge for organisms
with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by
known regulatory schemes acting at equilibrium, including variants of
cooperativity and combinatorial regulation. Our results suggest that crosstalk
imposes a previously unexplored global constraint on the functioning and
evolution of regulatory networks, which is qualitatively distinct from the known
constraints that act at the level of individual gene regulatory elements.
PMID- 27489146
TI - Bioremediation at a global scale: from the test tube to planet Earth.
AB - Planet Earth's biosphere has evolved over billions of years as a balanced bio
geological system ultimately sustained by sunpower and the large-scale cycling of
elements largely run by the global environmental microbiome. Humans have been
part of this picture for much of their existence. But the industrial revolution
started in the XIX century and the subsequent advances in medicine, chemistry,
agriculture and communications have impacted such balances to an unprecedented
degree - and the problem has nothing but exacerbated in the last 20 years. Human
overpopulation, industrial growth along with unsustainable use of natural
resources have driven many sites and perhaps the planetary ecosystem as a whole,
beyond recovery by spontaneous natural means, even if the immediate causes could
be stopped. The most conspicuous indications of such a state of affairs include
the massive change in land use, the accelerated increase in the levels of
greenhouse gases, the frequent natural disasters associated to climate change and
the growing non-recyclable waste (e.g. plastics and recalcitrant chemicals) that
we release to the Environment. While the whole planet is afflicted at a global
scale by chemical pollution and anthropogenic emissions, the ongoing development
of systems and synthetic biology, metagenomics, modern chemistry and some key
concepts from ecological theory allow us to tackle this phenomenal challenge and
propose large-scale interventions aimed at reversing and even improving the
situation. This involves (i) identification of key reactions or processes that
need to be re-established (or altogether created) for ecosystem reinstallation,
(ii) implementation of such reactions in natural or designer hosts able to self
replicate and deliver the corresponding activities when/where needed in a fashion
guided by sound ecological modelling, (iii) dispersal of niche-creating agents at
a global scale and (iv) containment, monitoring and risk assessment of the whole
process.
PMID- 27489147
TI - Testosterone Deficiency and Bone Metabolism Damage in Testicular Cancer
Survivors.
AB - The aim of the study was to investigate the influence of therapeutic modalities
and sexual hormone levels on changes in bone mineral density (BMD) in testicular
cancer (TC) survivors. In a cross-sectional descriptive, long-term follow-up
study, a total of 1,249 long-term TC survivors were evaluated according to
treatment modality: orchiectomy (OE) only, OE + chemotherapy (CT), or OE +
radiotherapy (RT). Luteinizing hormone (LH), total testosterone (TST), marker of
bone resorption (beta-carboxyl-terminal cross-linking telopeptide of type I
collagen-CTx), and BMD were evaluated. Standard statistical techniques were used
to test the differences between groups of patients. TST decrease was observed in
46/313 TC survivors after OE alone, in 103/665 after OE + CT, and in 66/271 after
OE + RT. LH increase was observed in 23/313 TC survivors after OE alone, in
154/665 after OE + CT, and in 43/271 after OE + RT. CTx increase was observed in
116/313 TC survivors after OE alone, in 324/665 after OE + CT, and in 82/271
after OE + RT. Osteopenia/osteoporosis occurred in 136/313 TC survivors after OE
alone, in 298/665 after OE + CT, and in 139/271 after OE + RT. TC survivors after
RT have statistically significant decreased TST levels, increased LH and
nonsignificant worse BMD (osteopenia/osteoporosis) in comparison with TC
survivors after OE alone or CT. TST decrease and LH increase were statistically
significant, more frequently observed in patients with osteopenia/osteoporosis.
Examination of TST is an important part of follow-up in TC survivors with
bilateral as well as unilateral disease. The important part of standard
examination algorithm should be also the osteological examination of TC survivors
mainly in patients with androgen deficiency.
PMID- 27489148
TI - Pulmonary Function of Young Muslim Males During the Month of Ramadan: Some Points
to Highlight.
PMID- 27489149
TI - Correction: Decision analytic cost-effectiveness model to compare prostate
cryotherapy to androgen deprivation therapy for treatment of radiation recurrent
prostate cancer.
PMID- 27489150
TI - Correction: Effect modification of FADS2 polymorphisms on the association between
breastfeeding and intelligence: protocol for a collaborative meta-analysis.
PMID- 27489151
TI - Cross-sectional study exploring barriers to adverse drug reactions reporting in
community pharmacy settings in Dhaka, Bangladesh.
AB - OBJECTIVES: To assess community pharmacists'/pharmacy technicians' knowledge and
perceptions about adverse drug reactions (ADRs) and barriers towards the
reporting of such reactions in Dhaka, Bangladesh. METHOD: A cross-sectional study
was planned to approach potential respondents for the study. A self-administered
questionnaire was delivered to community pharmacists/pharmacy technicians (N=292)
practising in Dhaka, Bangladesh. RESULTS: The overall response to the survey was
69.5% (n=203). The majority of the sample was comprised of pharmacy technicians
(152, 74.9%) who possessed a diploma in pharmacy, followed by pharmacists (37,
18.2%) and others (12, 5.9%). Overall, 72 (35.5%) of the respondents disclosed
that they had experienced an ADR at their pharmacy, yet more than half (105,
51.7%) were not familiar with the existence of an ADR reporting body in
Bangladesh. Exploring the barriers to the reporting of ADRs, it was revealed that
the top four barriers to ADR reporting were 'I do not know how to report
(Relative Importance Index (RII)=0.998)', 'reporting forms are not available
(0.996)', 'I am not motivated to report (0.997)' and 'Unavailability of
professional environment to discuss about ADR (RII=0.939)'. In addition to these,
a majority (141, 69.46%) were not confident about the classification of ADRs
(RII=0.889) and were afraid of legal liabilities associated with reporting ADRs
(RII=0.806). Moreover, a lack of knowledge about pharmacotherapy and the
detection of ADRs was another major factor hindering their reporting (RII=0.731).
CONCLUSIONS: The Directorate of Drug Administration in Bangladesh needs to
consider the results of this study to help it improve and simplify ADR reporting
in Bangladeshi community pharmacy settings.
PMID- 27489152
TI - Interleukin-1beta and tumour necrosis factor-alpha levels in conjunctiva of
diabetic patients with symptomatic moderate dry eye: case-control study.
AB - OBJECTIVES: To compare expression of interleukin (IL)-1beta and tumour necrosis
factor (TNF)-alpha in the conjunctiva of diabetic and non-diabetic patients with
symptomatic moderate dry eye. SETTING AND PARTICIPANTS: Nineteen diabetic
patients with dry eye, 15 non-diabetic patients with dry eye and 14 diabetic
patients without dry eye were recruited. The relative expression of IL-1beta and
TNF-alpha in conjunctival impression cytology (CIC) specimens was evaluated using
immunofluorescent staining and in conjunctival biopsy specimens using
immunohistochemical staining. RESULTS: The diabetic dry eye group showed
significantly higher grades of metaplasia than the non-diabetic dry eye and
diabetic without dry eye groups (both p<0.05). There was no significant
difference in the concentration of IL-1beta and TNF-alpha in CIC specimens
between the three groups (p=0.504 and p=0.310, respectively). The mean levels of
IL-1beta and TNF-alpha in conjunctival biopsy specimens from the diabetic dry eye
group was significantly increased compared with the non-diabetic dry eye and
diabetic without dry eye groups (p=0.002, p<0.001; p=0.001, p<0.001,
respectively). Interestingly, IL-1beta- and TNF-alpha-positive cells were mainly
located in the basal layer of the conjunctival epithelium, and rarely seen in the
apical conjunctival epithelium in the three groups. The levels of both IL-1beta
and TNF-alpha did not correlate with conjunctival squamous metaplasia grades.
CONCLUSIONS: Levels of IL-1beta and TNF-alpha in conjunctival biopsy specimens
were increased in diabetic patients with dry eye, while levels of IL-1beta and
TNF-alpha in apical conjunctival epithelium were similar in the CIC specimens.
These findings suggest that the inflammatory response is not limited to the
surface of conjunctival epithelial cells, and is more serious in the basal layer
of the epithelium, which may play an important role in the pathogenesis of dry
eye in diabetic patients.
PMID- 27489153
TI - Effectiveness of one-to-one volunteer support for patients with psychosis:
protocol of a randomised controlled trial.
AB - INTRODUCTION: Social isolation is common in patients with psychosis and
associated with a number of negative outcomes. Programmes in which volunteers
provide one-to-one support-often referred to as befriending-have been reputed to
achieve favourable outcomes. However, trial-based evidence for their
effectiveness is limited. METHODS AND ANALYSIS: This is a randomised controlled
trial comparing the effects of one-to-one volunteer support with an active
control condition for patients with psychosis over a 1-year period. Patients in
the intervention group will receive the support of a volunteer for 1 year, who
will meet them weekly and engage them in social and recreational activities.
Patients in the control group will not receive support from a volunteer. In both
groups, patients will be given a booklet detailing locally available social
activities and otherwise receive treatment as usual. Patients, volunteers,
clinicians and researchers involved in the delivery of the intervention will not
be blinded to group assignment, while researchers carrying out data collection
will be blinded. Data collection will be conducted at baseline, at 6 and 12
months. The primary outcome is the amount of time spent engaging in social
activities per day. Secondary outcomes include symptoms, quality of life, self
esteem and costs of care. Attitudes of volunteers towards mentally ill people
will be assessed. Finally, in-depth interviews will be conducted with patients
and volunteers. ETHICS AND DISSEMINATION: The study has been approved by the
National Research Ethics Service (NRES) Committee London-Camden & Kings Cross
(reference 15/LO/0674). The findings of the trial will be published in open
access peer-reviewed journals and in the National Institute for Health Research
(NIHR) journals library, and presented at scientific conferences. In addition,
findings will be summarised for a lay audience and circulated to all relevant
National Health Service (NHS) and voluntary organisations. TRIAL REGISTRATION
NUMBER: ISRCTN14021839; Pre-results.
PMID- 27489154
TI - Bibliometric analysis of scientific publications in transplantation journals from
Mainland China, Japan, South Korea and Taiwan between 2006 and 2015.
AB - OBJECTIVES: The aim of this study is to compare the quantity and quality of
scientific publications in transplantation fields that were written by
researchers from Mainland China, Japan, South Korea and Taiwan in the East Asia
region. SETTINGS: East Asia. PARTICIPANTS AND OUTCOME MEASURES: Articles except
editorials, conference abstracts, letters, news and corrections published in 25
transplantation journals from 2006 to 2015 were screened with the Web of Science
database. The number of total and annual articles, article types (study design
and transplantation site), impact factor, citations and articles in the high
impact journals was determined to assess the quantity and quality of
transplantation research from East Asia. The correlation of socioeconomic factors
and annual publications was also analysed. RESULTS: From 2006 to 2015, there were
47 141 articles published in transplantation journals, of which researchers from
Japan published 3694 articles, followed by Mainland China, South Korea and Taiwan
with 2778, 1643 and 951 articles, respectively. Similar trends were observed in
accumulated impact factor, accumulated citations, articles in the high-impact
journals and articles on transplantation site. Publications from Japan had the
highest average impact factor and citation, while those from Mainland China had
the lowest. Additionally, in terms of study design, authors from Mainland China
contributed to most clinical trials and randomised controlled trials, but authors
from Japan contributed to most case reports. The annual numbers of articles from
Mainland China and South Korea increased linearly (p<0.05), but those from Japan
and Taiwan remained stable for the period studied. The annual numbers of articles
from Mainland China and South Korea were positively correlated with gross
domestic product (p<0.05). CONCLUSIONS: Transplantation research productivity in
East Asia is highly skewed, with gross domestic product having a significant
positive correlation. Mainland China still lags far behind Japan in most
bibliometric indicators; thus, there is vast room for improvement.
PMID- 27489155
TI - Long-term changes in the heat-mortality relationship according to heterogeneous
regional climate: a time-series study in South Korea.
AB - OBJECTIVES: Several studies identified a heterogeneous impact of heat on
mortality in hot and cool regions during a fixed period, whereas less evidence is
available for changes in risk over time due to climate change in these regions.
We compared changes in risk during periods without (1996-2000) and with (2008
2012) heatwave warning forecasts in regions of South Korea with different
climates. METHODS: Study areas were categorised into 3 clusters based on the
spatial clustering of cooling degree days in the period 1993-2012: hottest
cluster (cluster H), moderate cluster (cluster M) and cool cluster (cluster C).
The risk was estimated according to increases in the daily all-cause,
cardiovascular and respiratory mortality per 1 degrees C change in daily
temperature above the threshold, using a generalised additive model. RESULTS: The
risk of all types of mortality increased in cluster H in 2008-2012, compared with
1996-2000, whereas the risks in all-combined regions and cooler clusters
decreased. Temporal increases in mortality risk were larger for some vulnerable
subgroups, including younger adults (<75 years), those with a lower education and
blue-collar workers, in cluster H as well as all-combined regions. Different
patterns of risk change among clusters might be attributable to large increases
in heatwave frequency or duration during study periods and the degree of
urbanisation in cluster H. CONCLUSIONS: People living in hotter regions or with a
lower socioeconomic status are at higher risk following an increasing trend of
heat-related mortality risks. Continuous efforts are needed to understand factors
which affect changes in heat-related mortality risks.
PMID- 27489156
TI - Does a mandibular overdenture improve nutrient intake and markers of nutritional
status better than conventional complete denture? A systematic review and meta
analysis.
AB - OBJECTIVES: The need for denture treatment in public health will increase as the
population ages. However, the impact of dentures on nutrition, particularly
overdenture treatment, remains unclear although the physical and psychological
effects are known. We investigated whether treatment with a mandibular implant
supported overdenture improves nutrient intake and markers of nutritional status
better than a conventional complete denture in edentulous patients. DESIGN:
Systematic review and meta-analysis. METHODS: Medline, EMBASE and the Cochrane
Central Register of Controlled Trials were searched for eligible studies
published up to April 2016. We included studies which compared the treatment
effect of an overdenture to conventional denture on nutrition, in which primary
outcomes included changes in intake of macronutrients and/or micronutrients
and/or indicators of nutritional status. Two reviewers independently evaluated
eligible studies and assessed the risk of bias. We used a fixed effects model to
estimate the weighted mean difference (WMD) and 95% CI for change in body mass
index (BMI), albumin and serum vitamin B12 between overdenture and conventional
denture 6 months after treatment. RESULTS: Of 108 eligible studies, 8 studies
involving 901 participants were included in the narrative appraisal. Four studies
reported changes in markers of nutritional status and nutrient intake after
treatment with a prosthetic, regardless of type. In a meta-analysis of 322
participants aged 65 years or older from three studies, pooled analysis suggested
no significant difference in change in BMI between an overdenture and
conventional denture 6 months after treatment (WMD=-0.18 kg/m(2) (95% CI -0.52 to
0.16)), and no significant difference in change in albumin or vitamin B12 between
the two treatments. CONCLUSIONS: The modifying effect of overdenture treatment on
nutritional status might be limited. Further studies are needed to evaluate the
effectiveness and efficacy of denture treatments.
PMID- 27489157
TI - Live cumulative network meta-analysis: protocol for second-line treatments in
advanced non-small-cell lung cancer with wild-type or unknown status for
epidermal growth factor receptor.
AB - INTRODUCTION: Many second-line treatments for advanced non-small-cell lung cancer
(NSCLC) have been assessed in randomised controlled trials, but which treatments
work the best remains unclear. Novel treatments are being rapidly developed. We
need a comprehensive up-to-date evidence synthesis of all these treatments. We
present the protocol for a live cumulative network meta-analysis (NMA) to address
this need. METHODS AND ANALYSIS: We will consider trials of second-line
treatments in patients with advanced NSCLC with wild-type or unknown epidermal
growth factor receptor status. We will consider any single agent of cytotoxic
chemotherapy, targeted therapy, combination of cytotoxic chemotherapy and
targeted therapy and any combination of targeted therapies. The primary outcomes
will be overall survival and progression-free survival. The live cumulative NMA
will be initiated with a NMA and then iterations will be repeated at regular
intervals to keep the NMA up-to-date over time. We have defined the update
frequency as 4 months, based on an assessment of the pace of evidence production
on this topic. Each iteration will consist of six methodological steps: adaptive
search for treatments and trials, screening of reports and selection of trials,
data extraction, assessment of risk of bias, update of the network of trials and
synthesis, and dissemination. We will set up a research community in lung cancer,
with different groups of contributors of different skills. We will distribute
tasks through online crowdsourcing. This proof-of-concept study in second-line
treatments of advanced NSCLC will allow one for assessing the feasibility of live
cumulative NMA and opening the path for this new form of synthesis. ETHICS AND
DISSEMINATION: Ethical approval is not required because our study will not
include confidential participant data and interventions. The description of all
the steps and the results of this live cumulative NMA will be available online.
TRIAL REGISTRATION NUMBER: CRD42015017592.
PMID- 27489158
TI - Venous thromboembolism in medical patients during hospitalisation and 3 months
after hospitalisation: a prospective observational study.
AB - OBJECTIVES: This study was conducted to assess the incidence and risk factors for
venous thromboembolism (VTE) in a cohort of medical patients both during the
period of hospitalisation and following discharge. DESIGN: This was a prospective
observational study to document the risk profile and incidence of VTE
posthospitalisation among all medical patients admitted to our institution during
the trial period. SETTINGS: Primary healthcare. Single tertiary referral centre,
Tasmania, Australia. PARTICIPANTS: A total of 986 patients admitted to the
medical ward between January 2012 and September 2012 were included in the study
with male to female ratio of 497:489. The mean age of patients was 68 years
(range 17-112, SD 16). RESULTS: Overall, 54/986 patients (5.5%) had a VTE during
the study period. Of these, 40/54 (74.1%) occurred during hospitalisation and
14/54 (25.9%) occurred following discharge. VTE risk factors revealed in
multivariate analysis to be associated with a previous diagnosis of VTE (p<0.001,
OR=6.63, 95% CI 3.3 to 13.36), the occurrence of surgery within the past 30 days
(p<0.001, OR=2.52, 95% CI 1.33 to 4.79) and an admission diagnosis of pulmonary
disease (p<0.01, OR 3.61, 95% CI 1.49 to 8.76). Mobility within 24 hours of
admission was not associated with an increased risk. There was risk of VTE when
the length of stay prolonged (p=0.046, OR=1.01, 95% CI 1.00 to 1.03), however it
was not sustained with multivariate modelling. VTE-specific prophylaxis was used
in 53% of the studied patients. Anticoagulation including antiplatelet agents
were administered in 63% of patients who developed VTE. CONCLUSIONS: This
prospective observational study found that 5.5% of the studied patients developed
VTE. Among those, 25.9% (14/54) of patients had a detected VTE
posthospitalisation with this risk being increased if there was a history of VTE,
recent surgery and pulmonary conditions. Thromboprophylaxis may be worth
considering in these cohorts. Further study to confirm these findings are
warranted. TRIAL REGISTRATION NUMBER: ACTRN12611001255976.
PMID- 27489159
TI - Protocol of the PLeural Effusion And Symptom Evaluation (PLEASE) study on the
pathophysiology of breathlessness in patients with symptomatic pleural effusions.
AB - INTRODUCTION: Pleural effusion is a common clinical problem that can complicate
many medical conditions. Breathlessness is the most common symptom of pleural
effusion of any cause and the most common reason for pleural drainage. However,
improvement in breathlessness following drainage of an effusion is variable; some
patients experience either no benefit or a worsening of their breathlessness. The
physiological mechanisms underlying breathlessness in patients with a pleural
effusion are unclear and likely to be multifactorial with patient-related and
effusion-related factors contributing. A comprehensive study of the physiological
and symptom responses to drainage of pleural effusions may provide a clearer
understanding of these mechanisms, and may identify predictors of benefit from
drainage. The ability to identify those patients whose breathlessness will (or
will not) improve after pleural fluid drainage can help avoid unnecessary pleural
drainage procedures, their associated morbidities and costs. The PLeural Effusion
And Symptom Evaluation (PLEASE) study is a prospective study to comprehensively
evaluate factors contributing to pleural effusion-related breathlessness. METHODS
AND ANALYSIS: The PLEASE study is a single-centre prospective study of 150
patients with symptomatic pleural effusions that require therapeutic drainage.
The study aims to identify key factors that underlie breathlessness in patients
with pleural effusions and develop predictors of improvement in breathlessness
following effusion drainage. Participants will undergo evaluation pre-effusion
and post-effusion drainage to assess their level of breathlessness at rest and
during exercise, respiratory and other physiological responses as well as
respiratory muscle mechanics. Pre-drainage and post-drainage parameters will be
collected and compared to identify the key factors and mechanisms that correlate
with improvement in breathlessness. ETHICS AND DISSEMINATION: Approved by the Sir
Charles Gairdner Group Human Research Ethics Committee (HREC number 2014-079).
Registered with the Australian New Zealand Clinical Trials Registry
(ACTRN12616000820404). Results will be published in peer-reviewed journals and
presented at scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12616000820404;
Pre-results.
PMID- 27489160
TI - Are inter- and intraspecific variations of sapling crown traits consistent with a
strategy promoting light capture in tropical moist forest?
AB - BACKGROUND AND AIMS: Morphological variation in light-foraging strategies
potentially plays important roles in efficient light utilization and carbon
assimilation in spatially and temporally heterogeneous environments such as
tropical moist forest understorey. By considering a suite of morphological traits
at various hierarchical scales, we examined the functional significance of crown
shape diversity and plasticity in response to canopy openness. METHODS: We
conducted a field comparative study in French Guiana among tree saplings of 14 co
occurring species differing in light-niche optimum and breadth. Each leaf, axis
or crown functional trait was characterized by a median value and a degree of
plasticity expressed under contrasting light regimes. KEY RESULTS: We found
divergent patterns between shade-tolerant and heliophilic species on the one hand
and between shade and sun plants on the other. Across species, multiple
regression analysis showed that relative crown depth was positively correlated
with leaf lifespan and not correlated with crown vertical growth rate. Within
species displaying a reduction in crown depth in the shade, we observed that
crown depth was limited by reduced crown vertical growth rate and not by
accelerated leaf or branch shedding. In addition, the study provides contrasting
examples of morphological multilevel plastic responses, which allow the
maintenance of efficient foliage and enable effective whole-plant light capture
in shaded conditions under a moderate vertical light gradient. CONCLUSIONS: This
result suggests that plastic adjustment of relative crown depth does not reflect
a strategy maximizing light capture efficiency. Integrating and scaling-up leaf
level dynamics to shoot- and crown-level helps to interpret in functional and
adaptive terms inter- and intraspecific patterns of crown traits and to better
understand the mechanism of shade tolerance.
PMID- 27489161
TI - The moss Funaria hygrometrica has cuticular wax similar to vascular plants, with
distinct composition on leafy gametophyte, calyptra and sporophyte capsule
surfaces.
AB - BACKGROUND AND AIMS: Aerial surfaces of land plants are covered with a waxy
cuticle to protect against water loss. The amount and composition of cuticular
waxes on moss surfaces had rarely been investigated. Accordingly, the degree of
similarity between moss and vascular plant waxes, and between maternal and
offspring moss structure waxes is unknown. To resolve these issues, this study
aimed at providing a comprehensive analysis of the waxes on the leafy
gametophyte, gametophyte calyptra and sporophyte capsule of the moss Funaria
hygrometrica METHODS: Waxes were extracted from the surfaces of leafy
gametophytes, gametophyte calyptrae and sporophyte capsules, separated by gas
chromatography, identified qualitatively with mass spectrometry, and quantified
with flame ionization detection. Diagnostic mass spectral peaks were used to
determine the isomer composition of wax esters. KEY RESULTS: The surfaces of the
leafy gametophyte, calyptra and sporophyte capsule of F. hygrometrica were
covered with 0.94, 2.0 and 0.44 MUg cm(-2) wax, respectively. While each wax
mixture was composed of mainly fatty acid alkyl esters, the waxes from maternal
and offspring structures had unique compositional markers. beta-Hydroxy fatty
acid alkyl esters were limited to the leafy gametophyte and calyptra, while
alkanes, aldehydes and diol esters were restricted to the sporophyte capsule.
Ubiquitous fatty acids, alcohols, fatty acid alkyl esters, aldehydes and alkanes
were all found on at least one surface. CONCLUSIONS: This is the first study to
determine wax coverage (MUg cm(-2)) on a moss surface, enabling direct
comparisons with vascular plants, which were shown to have an equal amount or
more wax than F. hygrometrica Wax ester biosynthesis is of particular importance
in this species, and the ester-forming enzyme(s) in different parts of the moss
may have different substrate preferences. Furthermore, the alkane-forming wax
biosynthesis pathway, found widely in vascular plants, is active in the
sporophyte capsule, but not in the leafy gametophyte or calyptra. Overall, wax
composition and coverage on F. hygrometrica were similar to those reported for
some vascular plant species, suggesting that the underlying biosynthetic
processes in plants of both lineages were inherited from a common ancestor.
PMID- 27489162
TI - Small-Molecule Compounds Exhibiting Target-Mediated Drug Disposition (TMDD): A
Minireview.
AB - Nonlinearities are commonplace in pharmacokinetics, and 1 special source is the
saturable binding of the drug to a high-affinity, low-capacity target, a
phenomenon known as target-mediated drug disposition (TMDD). Compared with large
molecule compounds undergoing TMDD, which has been well recognized due to its
high prevalence, TMDD in small-molecule compounds is more counterintuitive and
has not been well appreciated. With more and more potent small-molecule drugs
acting on highly specific targets being developed as well as increasingly
sensitive analytical techniques becoming available, many small-molecule compounds
have recently been reported to have nonlinear pharmacokinetics imparted by TMDD.
To expand our current knowledge of TMDD in small-molecule compounds and increase
the awareness of this clinically important phenomenon, this minireview provides
an overview of the small-molecule compounds that demonstrate nonlinear
pharmacokinetics imparted by TMDD. The present review also summarizes the general
features of TMDD in small-molecule compounds and highlights the differences
between TMDD in small-molecule compounds and large-molecule compounds.
PMID- 27489163
TI - Eicosapentaenoic Acid Potentiates Brown Thermogenesis through FFAR4-dependent Up
regulation of miR-30b and miR-378.
AB - Emerging evidence suggests that n-3 polyunsaturated fatty acids (PUFA) promote
brown adipose tissue thermogenesis. However, the underlying mechanisms remain
elusive. Here, we hypothesize that n-3 PUFA promotes brown adipogenesis by
modulating miRNAs. To test this hypothesis, murine brown preadipocytes were
induced to differentiate the fatty acids of palmitic, oleate, or eicosapentaenoic
acid (EPA). The increases of brown-specific signature genes and oxygen
consumption rate by EPA were concurrent with up-regulation of miR-30b and 378 but
not by oleate or palmitic acid. Next, we hypothesize that free fatty acid
receptor 4 (Ffar4), a functional receptor for n-3 PUFA, modulates miR-30b and
378. Treatment of Ffar4 agonist (GW9508) recapitulated the thermogenic activation
of EPA by increasing oxygen consumption rate, brown-specific marker genes, and
miR-30b and 378, which were abrogated in Ffar4-silenced cells. Intriguingly,
addition of the miR-30b mimic was unable to restore EPA-induced Ucp1 expression
in Ffar4-depleted cells, implicating that Ffar4 signaling activity is required
for up-regulating the brown adipogenic program. Moreover, blockage of miR-30b or
378 by locked nucleic acid inhibitors significantly attenuated Ffar4 as well as
brown-specific signature gene expression, suggesting the signaling interplay
between Ffar4 and miR-30b/378. The association between miR-30b/378 and brown
thermogenesis was also confirmed in fish oil-fed C57/BL6 mice. Interestingly, the
Ffar4 agonism-mediated signaling axis of Ffar4-miR-30b/378-Ucp1 was linked with
an elevation of cAMP in brown adipocytes, similar to cold-exposed or fish oil-fed
brown fat. Taken together, our work identifies a novel function of Ffar4 in
modulating brown adipogenesis partly through a mechanism involving cAMP
activation and up-regulation of miR-30b and miR-378.
PMID- 27489164
TI - Soluble egg antigens of Schistosoma japonicum induce senescence in activated
hepatic stellate cells by activation of the STAT3/p53/p21 pathway.
AB - Liver fibrosis is characterized by the activation of hepatic stellate cells
(HSCs). Recent findings suggest that senescence of activated HSCs might limit the
development of liver fibrosis. Based on previously observed anti-fibrotic effects
of soluble egg antigens from Schistosoma japonicum in vitro, we hypothesized that
SEA might play a crucial role in alleviating liver fibrosis through promoting
senescence of activated HSCs. We show here that SEA inhibited expression of alpha
SMA and pro-collagen I and promoted senescence of activated HSCs in vitro. In
addition, SEA induced an increased expression of P-p53 and p21. Knockdown of p53
inhibited the expression of p21 and failed to induce senescence of activated
HSCs. Phosphorylated STAT3 was elevated upon SEA stimulation, while loss of STAT3
decreased the level of p53 and senescence of HSCs. Results from
immunoprecipitation analysis demonstrated that SOCS3 might be involved in the SEA
induced senescence in HSCs through its interaction with p53. This study
demonstrates the potential capacity of SEA in restricting liver fibrosis through
promoting senescence in HSCs. Furthermore, a novel STAT3-p53-p21 pathway might
participate in the observed SEA-mediated senescence of HSCs. Our results suggest
that SEA might carry potential therapeutic effects of restraining liver fibrosis
through promoting senescence.
PMID- 27489165
TI - Pipeline Embolization Device for Small Intracranial Aneurysms: Evaluation of
Safety and Efficacy in a Multicenter Cohort.
AB - BACKGROUND: To date, the use of the flow-diverting Pipeline Embolization Device
(PED) for small intracranial aneurysms (<= 7 mm) has been reported only in single
center series. OBJECTIVE: To evaluate the safety and efficacy of the PED in a
multicenter cohort. METHODS: Five major academic institutions in the United
States provided data on patient demographics, aneurysm features, and treatment
characteristics of consecutive patients with aneurysms <= 7 mm treated with a PED
between 2009 and 2015. Radiographic outcome was assessed with digital subtraction
angiography. Clinical outcome was measured with the modified Rankin Scale.
RESULTS: The cumulative number of aneurysms <= 7 mm treated with PED at the 5
institutions was 149 in 117 patients (age, 54 years [range, 29-87 years]; male to
female, 1-5.9). Aneurysms were most commonly located in the paraophthalmic
segment (67.1%) of the internal carotid artery. Radiographic outcome at last
follow-up was available for 123 aneurysms (82.6%), with a complete occlusion rate
of 87%. Thromboembolic and symptomatic procedural complications occurred in 8.7%
and 6% of the aneurysms treated, respectively. There was 1 mortality (0.9%)
unrelated to the PED procedure. Multivariable logistic regression identified size
< 4 mm, balloon angioplasty to open the device, and simultaneous treatment of
multiple aneurysms as predictors of procedural complications. Good clinical
outcome was achieved in 96% of electively treated patients. CONCLUSION: In the
largest series on PED for small aneurysms to date, data suggest that treatment
with the flow-diverting PED is safe and efficacious, with complication rates
comparable to those for traditional endovascular techniques.
PMID- 27489166
TI - Syndrome of the Trephined: A Systematic Review.
AB - BACKGROUND: Syndrome of the trephined (SoT) is a rare, important complication of
a craniectomy characterized by neurological dysfunction that improves with
cranioplasty. Its varied symptoms include motor, cognitive, and language
deficits. Its exact characterization appears suboptimal, with differing
approaches of evaluation. Accordingly, this topic is in great need of further
investigation. OBJECTIVE: To accurately describe SoT and explore methods of an
objective diagnosis/evaluation. METHODS: Electronic searches of PubMed, MEDLINE,
Web of Knowledge, and PsycINFO databases used the key words "syndrome of the
trephined" and "sinking skin flap." Non-English-language and duplicate articles
were eliminated. Title and abstract reviews were selected for relevance. Full
text reviews were selected for articles providing individual characteristics of
SoT patients. RESULTS: This review identified that SoT most often occurs in male
patients (60%) at 5.1 +/- 10.8 months after craniectomy for neurotrauma (38%).
The average reported craniectomy is 88.3 +/- 34.4 cm and usually exists with a
"sunken skin flap" (93%). Symptoms most commonly include motor, cognitive, and
language deficits (57%, 41%, 28%, respectively), with improvement after
cranioplasty within 3.8 +/- 3.9 days. Functional independence with activities of
daily living is achieved by 54.9% of patients after 2.9 +/- 3.4 months of
rehabilitation. However, evaluation of SoT is inconsistent, with only 53% of
reports documenting objective studies. DISCUSSION: SoT is a variable phenomenon
associated with a prolonged time to cranioplasty. Due to current weaknesses in
objectivity, we hypothesize that SoT is often underdiagnosed and recommend a
multifaceted approach for consistent evaluation. CONCLUSION: SoT is a serious
complication that lacks exact characterization and deserves future investigation.
Improved understanding and recognition have important implications for early
intervention and patient outcomes. ABBREVIATIONS: ADLs, activities of daily
livingCBF, cerebral blood flowSoT, syndrome of the trephinedVP,
ventriculoperitoneal.
PMID- 27489167
TI - Identification and Cost of Potentially Avoidable Transfers to a Tertiary Care
Neurosurgery Service: A Pilot Study.
AB - BACKGROUND: Thousands of neurosurgical emergencies are transferred yearly to
tertiary care facilities to assume a higher level of care. Several studies have
examined how neurosurgical transfers influence patient outcomes, but
characteristics of potentially avoidable transfers have yet to be investigated.
OBJECTIVE: To identify whether potentially avoidable transfers represent a
significant portion of transfers to a tertiary neurosurgical facility. METHODS:
In this cohort study, we evaluated 916 neurosurgical patients transferred to a
tertiary care facility over a 2-year period. Transfers were classified as
potentially avoidable when no neurosurgical diagnostic test, intervention, or
intensive monitoring was deemed necessary (n = 180). The remaining transfers were
classified as justifiable (n = 736). The main outcomes and measures were age,
sex, diagnosis, insurance status, intervention, distance of transfer, length of
hospital and intensive care unit stay, mortality, discharge disposition, and
cost. RESULTS: Nearly 20% of transfers were identified as being potentially
avoidable. Although some of these patients had suffered devastating,
irrecoverable neurological insults, many had innocuous conditions that did not
require transfer to a higher level of care. Justifiable transfers tend to involve
patients with nontraumatic intracranial hemorrhage and cranial neoplasm. Both
groups were admitted to the intensive care unit at the same rate (approximately
70% of patients). Finally, the direct transportation cost of potentially
avoidable transfers was $1.46 million over 2 years. CONCLUSION: This study
identified the frequency and expense of potentially avoidable transfers. There is
a need for closer examination of the clinical and financial implications of
potentially avoidable transfers. ABBREVIATIONS: CI, confidence intervalIQR,
interquartile rangeJT, justifiable transferOR, odds ratioPAT, potentially
avoidable transferUAB, University of Alabama at Birmingham.
PMID- 27489168
TI - Inappropriate behaviors and hypersexuality in individuals with dementia: An
overview of a neglected issue.
AB - Behavioral and psychological symptoms of dementia are very common in patients
affected by dementia, and are associated with high rates of institutionalization.
Behavioral and psychological symptoms of dementia consist of aggressive behavior,
delusions, hallucinations, depression, apathy, wandering, stereotyped and
inappropriate sexual behavior. Interestingly, the latter has been reported to be
relatively uncommon, but causing immense distress to patients and their
caregivers. The genesis of inappropriate behavior is considered a combination of
neurological, psychological and social factors. Although assessment is mainly
carried out by clinical observation and interviews with caregivers, the most
appropriate management of behavioral and psychological symptoms of dementia,
including hypersexuality, is a combination of pharmacological and non
pharmacological interventions, according to specific symptoms, degree of
cognitive dysfunction and subtype of dementia. The present narrative review will
mainly focus on aggressiveness, disinhibition, aberrant motor, and sexually
inappropriate behavior diagnostic work-up and treatment, in an attempt to provide
both the patients and their caregivers with useful information to better manage
these symptoms and improve their quality of life. Space is particularly dedicated
to inappropriate sexual behavior, which is still considered a neglected issue.
Geriatr Gerontol Int 2017; 17: 865-874.
PMID- 27489169
TI - Testosterone for Poor Ovarian Responders: Lessons From Ovarian Physiology.
AB - Testosterone, an androgen that directly binds to the androgen receptor, has been
shown in previous small randomized controlled trials to increase the reproductive
outcomes of poor ovarian responders. In most of these studies, transdermal
testosterone in relatively high doses was administered before ovarian stimulation
with a duration varying from 5 to 21 days. Nevertheless, the key question to be
asked is whether, based on ovarian physiology and testosterone pharmacokinetics,
a short course of testosterone administration of more than 10 mg could be
expected to have any beneficial effect on reproductive outcome. The rationale for
asking this question lies in the existing scientific evidence derived from basic
research and animal studies regarding the action of androgens during
folliculogenesis, showing that their main effect in follicular development is
defined during the earlier developmental stages. In addition, extreme
testosterone excess is not only likely to induce adverse events but has also the
potential to be ineffective and even detrimental. Thus, evidence from clinical
studies is not enough to either "reopen" or "close" the "androgen chapter" in
poor responders, mainly because the short administration and the high dose of
testosterone is not in line with the ovarian actions of androgens and the
presence of androgen receptors during follicular development.
PMID- 27489170
TI - Using the placebo effect: how expectations and learned immune function can
optimize dermatological treatments.
AB - The role of placebo and nocebo effects-that is positive or negative treatment
effects that are entirely a consequence of the patient's expectations and beliefs
about a treatment outcome in terms of efficacy, safety, usability or side effects
has been shown for almost all types of diseases and physiological response
systems. Evidence for the relevance of placebo and nocebo effects in dermatology
is also increasing, particularly for symptoms of itch and learned (conditioned)
immune function. In addition, increasing knowledge is available about the
neurobiological mechanisms of action, such as the role of the dopaminergic
system. Studies on this topic offer innovative perspectives to unravel the
multifactorial pathways of treatment effects and to use research designs for
experimental research that provide full insight into the role of placebo and
nocebo effects. Moreover, intervention strategies can be developed for
dermatology practice that optimize regular treatments with innovative non
pharmacological treatment strategies (e.g. optimized doctor-patient communication
and treatment adherence, or prevention of nocebo reactions with regard to adverse
side effects). In addition, evidence on learned immune function offers new
pathways to optimize pharmacological treatments (e.g. dosage adjustments and
conditioning of physiological responses), the ultimate goal being to prevent
individual treatment failures and maximize regular treatment effects.
PMID- 27489171
TI - 'I didn't see that coming': simulated visual fields and driving hazard perception
test performance.
AB - BACKGROUND: Evidence is limited regarding specific types of visual field loss
associated with unsafe driving. We use novel gaze-contingent software to examine
the effect of simulated visual field loss on computer-based driving hazard
detection with the specific aim of testing the impact of scotomata located to the
right and left of fixation. METHODS: The 'hazard perception test' is a component
of the UK driving licence examination, which measures speed of detecting 15
different hazards in a series of real-life driving films. We have developed a
novel eye-tracking and computer set up capable of generating a realistic gaze
contingent scotoma simulation (GazeSS) overlaid on film content. Thirty drivers
with healthy vision completed three versions of the hazard perception test in a
repeated measures experiment. In two versions, GazeSS simulated a scotoma in the
binocular field of view to the left or right of fixation. A third version was
unmodified to establish baseline performance. RESULTS: Participants' mean
baseline hazard perception test score was 51 +/- 7 (out of 75). This reduced to
46 +/- 9 and 46 +/- 11 when completing the task with a binocular visual field
defect located to the left and right of fixation, respectively. While the main
effect of simulated visual field loss on performance was statistically
significant (p = 0.007), there were no average differences in the experimental
conditions where a scotoma was located in the binocular visual field to the right
or left of fixation. CONCLUSION: Simulated visual field loss impairs driving
hazard detection on a computer-based test. There was no statistically significant
difference in average performance when the simulated scotoma was located to the
right or left of fixation of the binocular visual field, but certain types of
hazard caused more difficulties than others.
PMID- 27489172
TI - On the positional and orientational order of water and methanol around indole: a
study on the microscopic origin of solubility.
AB - Although they are both highly polar liquids, there are a number of compounds,
such as many pharmaceuticals, which show vastly different solubilities in
methanol compared with water. From theories of the hydrophobic effect, it might
be predicted that this enhanced solubility is due to association between drugs
and the less polar -CH3 groups on methanol. In this work, detailed analysis on
the atomic structural interactions between water, methanol and the small molecule
indole - which is a precursor to many drugs and is sparingly soluble in water yet
highly soluble in methanol - reveal that indole preferentially interacts with
both water and methanol via electrostatic interactions rather than with direction
interactions to the -CH3 groups. The presence of methanol hydrogen bonds with pi
electrons of the benzene ring of indole can explain the increase in solubility of
indole in methanol relative to water. In addition, the excess entropy
calculations performed here suggest that this solvation is enthalpically rather
than entropically driven.
PMID- 27489173
TI - A Non-Exploding Alkali Metal Drop on Water: From Blue Solvated Electrons to
Bursting Molten Hydroxide.
AB - Alkali metals in water are always at the brink of explosion. Herein, we show that
this vigorous reaction can be kept in a non-exploding regime, revealing a
fascinating richness of hitherto unexplored chemical processes. A combination of
high-speed camera imaging and visible/near-infrared/infrared spectroscopy allowed
us to catch and characterize the system at each stage of the reaction. After
gently placing a drop of a sodium/potassium alloy on water under an inert
atmosphere, the production of solvated electrons became so strong that their
characteristic blue color could be observed with the naked eye. The exoergic
reaction leading to the formation of hydrogen and hydroxide eventually heated the
alkali metal drop such that it became glowing red, and part of the metal
evaporated. As a result of the reaction, a perfectly transparent drop consisting
of molten hydroxide was temporarily stabilized on water through the Leidenfrost
effect, bursting spectacularly after it had cooled sufficiently.
PMID- 27489174
TI - HDL subfractions and very early CAD: novel findings from untreated patients in a
Chinese cohort.
AB - Coronary artery disease (CAD) in very young individuals is a rare disease
associated with poor prognosis. However, the role of specific lipoprotein
subfractions in very young CAD patients (<=45 years) is not established yet. A
total of 734 consecutive CAD subjects were enrolled and were classified as very
early (n = 81, <=45), early (n = 304, male: 45-55; female: 45-65), and late (n =
349, male: >55; female: >65) groups. Meanwhile, a group of non-CAD subjects were
also enrolled as controls (n = 56, <=45). The lipoprotein separation was
performed using Lipoprint System. As a result, the very early CAD patients have
lower large high-density lipoprotein (HDL) subfraction and higher small low
density lipoprotein (LDL) subfraction (p < 0.05). Although body mass index was
inversely related to large HDL subfraction, overweight did not influence its
association with very early CAD. In the logistic regression analysis, large HDL
was inversely [OR 95% CI: 0.872 (0.825-0.922)] while small LDL was positively
[1.038 (1.008-1.069)] related to very early CAD. However, after adjusting
potential confounders, the association was only significant for large HDL [0.899
(0.848-0.954)]. This study firstly demonstrated that large HDL subfraction was
negatively related to very early CAD suggestive of its important role in very
early CAD incidence.
PMID- 27489175
TI - The MEEK technique: 10-year experience at a tertiary burn centre.
AB - Extensive full-thickness burns pose a great challenge to the burn surgeon. Lack
of autograft donor sites is an important limiting factor to achieving wound
closure. To overcome this problem, various methods of treatment have been
suggested in the past, including the MEEK technique. This study was carried out
at the Bogenhausen Hospital Burn Unit, Munich, Germany from 2006 to 2015. There
were a total of 148 skin grafting operations. The modified MEEK technique was
performed on 67 patients. Patients included 34 males and 33 females, with an
average age of 39.6 years. The mean percentage body surface burned was 65%, and
full-thickness injury occurred in 52%. The mean area graft per procedure was 20%.
The viability of the graft as assessed between the 7th and 10th day was generally
in the range of 60-90%. The average number of operations required was 2.21. The
mean length of stay was 27 days. Infection was documented in five patients, and
seven deaths occurred. The mean follow-up was 3.2 years. When faced with large
surface area burns and limited donor sites, the MEEK technique is a satisfactory
method for coverage.
PMID- 27489176
TI - Crucial Role Reported for TSPO in Viability and Steroidogenesis is a
Misconception. Commentary: Conditional Steroidogenic Cell-Targeted Deletion of
TSPO Unveils a Crucial Role in Viability and Hormone-Dependent Steroid Formation.
PMID- 27489177
TI - Both monovalent cations and plectin are potent modulators of mechanical
properties of keratin K8/K18 networks.
AB - Intermediate filament (IF) networks are a major contributor to cell rigidity and
thus serve as vital elements to preserve the integrity of entire cell layers.
Keratin K8 and K18 IFs are the basic constituents of the cytoskeleton of
epithelial cells. The mechanical properties of K8/K18 networks depend on the
structural arrangements of individual filaments within the network. This paper
investigates the architecture of these networks in vitro under the influence of
the monovalent cation potassium and that of the cytolinker protein plectin.
Whereas increasing amounts of potassium ions lead to filament bundling, plectin
interlinks filaments at filament intersection points but does not lead to bundle
formation. The mechanics of the resulting networks are investigated by
microrheology with assembled K8/K18 networks. It is shown that bundling induced
by potassium ions significantly stiffens the network. Furthermore, our
measurements reveal an increase in plectin-mediated keratin network rigidity as
soon as an amount corresponding to more than 20% of the plectin present in cells
is added to the keratin IF networks. In parallel, we investigated the influence
of plectin on cell rigidity in detergent-extracted epithelial vulva carcinoma
derived A431 cells in situ. These cytoskeletons, containing mostly IFs, actin
filaments and associated proteins, exhibit a significantly decreased stiffness,
when plectin is downregulated to ~10% of the normal value. Therefore, we assume
that plectin, via the formation of IF-IF connections and crosslinking of IFs to
actin filaments, is an important contributor to cell stiffness.
PMID- 27489178
TI - Acute migraine medication adherence, migraine disability and patient
satisfaction: A naturalistic daily diary study.
AB - Objective To examine the influence of acute migraine medication adherence on
migraine disability and acute medication satisfaction. Methods Adults with
migraine completed three months of daily electronic diaries assessing headache
symptoms, acute medication taken, acute medication satisfaction, and daily
migraine disability. Repeated measures mixed-effects models examined the effect
of initial medication type [migraine-specific medication (MSM) vs. over-the
counter analgesic (OTC) vs. an opiate/barbiturate], the severity of pain at
dosing, and their interaction with daily migraine disability and satisfaction
with acute medication. Results Participants (N = 337; 92.5% female; 91.1%
Caucasian, non-Hispanic; 84.0% with episodic migraine) recorded 29,722 diary
days. Participants took acute medication on 96.5% of 8090 migraine days. MSM was
most frequently taken first (58%), followed by OTC (29.9%) and an
opiate/barbiturate (12.1%). Acute medication was most frequently taken when pain
was mild (41.2%), followed by moderate (37.7%) and severe pain (11.4%). Initially
dosing with MSM while pain was mild was associated with the lowest daily
disability [medication * pain at dosing F (4, 6336.12) = 58.73, p < .001] and
highest acute medication satisfaction [medication * pain at dosing F (4, 3867.36)
= 24.00, p < .001]. Conclusion Using an MSM (triptan or ergot) first was
associated with the lowest migraine disability and highest acute medication
satisfaction.
PMID- 27489179
TI - A boy with bilateral SUNA: A case report.
AB - Background Short-lasting unilateral neuralgiform headache attacks (SUNA) is a
primary headache characterized by frequent attacks of severe headaches in
association with ipsilateral cranial autonomic features. SUNA is defined as a
strictly unilateral pain and bilateral cases are very unusual, so secondary
causes should be searched for vigorously if there are bilateral symptoms. Despite
a number of therapeutic trials, effective management for the majority of SUNA
patients is not available at present. Management of SUNA is often difficult. Case
We report the case of a young boy with bilateral SUNA attacks, with no detected
underlying cause, who is responsive to indomethacin. Conclusion Rarely, primary
SUNA can present with bilateral symptoms. According to our experience in this
case, indomethacin should always be offered to patients with suspected SUNA.
PMID- 27489180
TI - Oliver Sacks and migraine.
AB - Background Oliver Sacks (1933-2015) published a large number of books on a
variety of neurological topics. Of these, numerous copies have been sold and they
probably serve as the only or main source of information on neurological diseases
for many persons without a medical background. His first book was on migraine and
in his subsequent books many descriptions of migraine can be found, mainly those
of auras. Methods We explored the descriptions of migraine in Sacks' work in
order to evaluate the image of migraine offered to the readers. Conclusion Oliver
Sacks gave wonderful descriptions of migraine auras, but hardly any of migraine
headache. Furthermore, he described rare auras such as 'amusia' and olfactory
auras. Overall, this makes his descriptions of migraine not very useful to serve
as medical information for laypersons. Oliver Sacks, however, wrote great
literature.
PMID- 27489181
TI - Hyperargininemia and renal oxidative stress: Prevention by antioxidants and NG
nitro-l-arginine methyl ester.
AB - We investigated the in vitro and in vivo effects of arginine (Arg) on
thiobarbituric acid-reactive substances (TBA-RS) and on the activities of
catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD)
in renal tissues of rats. We also studied the influence of antioxidants (alpha
tocopherol plus ascorbic acid) and nitric oxide synthase inhibitor NG -nitro-l
arginine methyl ester (l-NAME) on the effects elicited by Arg. Results showed
that Arg in vitro (1.5 mM) decreased SOD activity and increased the levels of TBA
RS in the renal medulla. Acute administration of Arg [0.8 g/kg, intraperitoneal
injection] decreased CAT activity, increased SOD activity and TBA-RS levels in
the renal medulla, and decreased CAT activity in the renal cortex of rats. Most
results were prevented by antioxidants and/or l-NAME. Data indicate that Arg
causes an oxidative imbalance in the renal tissues studied; however, in the
presence of antioxidants and l-NAME, some of these alterations in oxidative
stress were prevented.
PMID- 27489182
TI - What can we learn about breathlessness from population-based and administrative
health data?
AB - PURPOSE OF REVIEW: To review the findings and methodological strengths and
limitations of studies of breathlessness using population-based or routinely
collected data, including the novel methodology of the registry-based randomized
controlled trial (R-RCT). RECENT FINDINGS: Breathlessness severe enough to
restrict activity is common and increases in the last months of life both among
elderly in the community and among patients in specialized palliative care.
During the last week of life, risk factors for more severe breathlessness have
been identified. Patients with advanced chronic obstructive or interstitial lung
disease experience more breathlessness than patients dying from lung cancer.
Breathlessness often remains unrelieved or only partially relieved at the end of
life. SUMMARY: Data from population-based or health-administrative databases can
inform on the epidemiology, associated factors and the potential impact of
breathlessness. Potential strengths of these data are high precision and
generalizability because of large, nonselective study populations with high
completeness of follow-up of outcomes such as survival. Potential limitations
include residual confounding and insufficient data quality which is unaffected by
increasing the sample size. The R-RCT methodology combines strengths of
randomization with those of large representative databases to evaluate
effectiveness in clinical care.
PMID- 27489183
TI - The evolving role of chemotherapy in prostate cancer.
PMID- 27489185
TI - The DnaA inhibitor SirA acts in the same pathway as Soj (ParA) to facilitate oriC
segregation during Bacillus subtilis sporulation.
AB - DNA replication and chromosome segregation must be carefully regulated to ensure
reproductive success. During Bacillus subtilis sporulation, chromosome copy
number is reduced to two, and cells divide asymmetrically to produce the future
spore (forespore) compartment. For successful sporulation, oriC must be captured
in the forespore. New rounds of DNA replication are prevented in part by SirA, a
protein that utilizes residues in its N-terminus to directly target Domain I of
the bacterial initiator, DnaA. Using a quantitative forespore chromosome
organization assay, we show that SirA also acts in the same pathway as another
DnaA regulator, Soj, to promote oriC capture in the forespore. By analyzing loss
of-function variants of both SirA and DnaA, we observe that SirA's ability to
inhibit DNA replication can be genetically separated from its role in oriC
capture. In addition, we identify substitutions near the C-terminus of SirA and
in DnaA Domain III that enhance interaction between the two proteins. One such
variant, SirAP141T , remained functional in regard to inhibiting replication, but
was unable to support oriC capture. Collectively, our results support a model in
which SirA targets DnaA Domain I to inhibit DNA replication, and DnaA Domain III
to facilitate Soj-dependent oriC capture in the forespore.
PMID- 27489186
TI - The influence of computerized interpretation of an electrocardiogram reading.
PMID- 27489187
TI - Cardiomyopathies: In vitro genetic correction of familial dilated cardiomyopathy.
PMID- 27489188
TI - Imaging: Cost-effectiveness of FFRCT-guided care.
PMID- 27489189
TI - Atherosclerosis: Treating atherosclerosis with antitumour antibodies.
PMID- 27489192
TI - Inflammation: Targeting the NLRP3 inflammasome after MI.
PMID- 27489191
TI - Antithrombotic therapy for secondary prevention of atherothrombotic events in
cerebrovascular disease.
AB - Atherothrombosis is the common underlying process for numerous progressive
manifestations of cardiovascular disease, including coronary artery disease (CAD)
and cerebrovascular disease (CVD). Antiplatelet therapy is the cornerstone of
pharmacological management in patients with atherothrombosis. Over the past 20
years, major advances in antiplatelet pharmacotherapy have been made,
particularly for the treatment of patients with CAD. The treatment of patients
with concomitant CAD and CVD is complex, owing to their increased risk of both
ischaemia and bleeding. When CVD arises from large artery atherosclerosis,
antithrombotic therapies are essential to prevent stroke or transient ischaemic
attack (TIA). However, the use of antithrombotic medications in patients with CVD
can put them at high risk of intracranial haemorrhage. As such, the risk-benefit
profile of various combinations of antiplatelet agents in patients with both CAD
and CVD is uncertain. This Review provides a state-of-the-art account of the
available evidence on antithrombotic therapies for the secondary prevention of
atherothrombotic events in patients with concomitant CAD and CVD, particularly
those with a history of noncardioembolic stroke or TIA.
PMID- 27489190
TI - Electrophysiological and molecular mechanisms of paroxysmal atrial fibrillation.
AB - Atrial fibrillation (AF) is an extremely prevalent arrhythmia that presents a
wide range of therapeutic challenges. AF usually begins in a self-terminating
paroxysmal form (pAF). With time, the AF pattern often evolves to become
persistent (nonterminating within 7 days). Important differences exist between
pAF and persistent AF in terms of clinical features, in particular the
responsiveness to antiarrhythmic drugs and ablation therapy. AF mechanisms have
been extensively reviewed, but few or no Reviews focus specifically on the
pathophysiology of pAF. Accordingly, in this Review, we examine the available
data on the electrophysiological basis for pAF occurrence and maintenance, as
well as the molecular mechanisms forming the underlying substrate. We first
consider the mechanistic insights that have been obtained from clinical studies
in the electrophysiology laboratory, noninvasive observations, and genetic
studies. We then discuss the information about underlying molecular mechanisms
that has been obtained from experimental studies on animal models and patient
samples. Finally, we discuss the data available from animal models with
spontaneous AF presentation, their relationship to clinical findings, and their
relevance to understanding the mechanisms underlying pAF. Our analysis then turns
to potential factors governing cases of progression from pAF to persistent AF and
the clinical implications of the basic mechanisms we review. We conclude by
identifying and discussing questions that we consider particularly important to
address through future research in this area.
PMID- 27489194
TI - Elevated nitric oxide levels associated with hepatic cell apoptosis during liver
injury.
AB - Hepatic injury is a major event in liver surgery such as liver transplantation
and it always leads to hepatic cell apoptosis. Nitric oxide (NO) is a key
signaling regulation molecule. Many researchers have shown that increased NO
level can influence liver cell apoptosis by promoting or inhibiting the relative
signaling pathways that are involved in the caspase family, Bax/Bcl-2,
mitochondria, oxidative stress, death receptors, and mitogen-activated protein
kinases. Elucidating the relationships between NO and hepatic cell apoptosis is
necessary for ameliorating prognosis of liver surgery. This article reviews the
newest research progress in the relationships between higher NO levels and
hepatic cell apoptosis in liver injury.
PMID- 27489193
TI - Parity-time-symmetry enhanced optomechanically-induced-transparency.
AB - We propose and analyze a scheme to enhance optomechanically-induced-transparency
(OMIT) based on parity-time-symmetric optomechanical system. Our results predict
that an OMIT window which does not exist originally can appear in weak
optomechanical coupling and driving system via coupling an auxiliary active
cavity with optical gain. This phenomenon is quite different from these reported
in previous works in which the gain is considered just to damage OMIT phenomenon
even leads to electromagnetically induced absorption or inverted-OMIT. Such
enhanced OMIT effects are ascribed to the additional gain which can increase
photon number in cavity without reducing effective decay. We also discuss the
scheme feasibility by analyzing recent experiment parameters. Our work provide a
promising platform for the coherent manipulation and slow light operation, which
has potential applications for quantum information processing and quantum optical
device.
PMID- 27489195
TI - Potentiation of luteolin cytotoxicity by flavonols fisetin and quercetin in human
chronic lymphocytic leukemia cell lines.
AB - Despite numerous studies chronic lymphocytic leukemia (CLL) still remains an
incurable disease. Therefore, all new compounds and novel strategies which are
able to eradicate CLL cells should be considered as valuable clues for a
potential future remedy against this malignancy. In the present study, the
cytotoxic profiles of natural flavonoids were described in two human CLL cell
lines, HG-3 and EHEB, indicating the flavone luteolin as the most potent
flavonoid with half-maximal inhibitory constants (IC50) of 37 MUM and 26 MUM,
respectively. Luteolin significantly increased the apoptotic cell population in
both cell lines by increasing the activities of caspases-3 and -9 and triggering
the intrinsic apoptotic pathway. Two flavonols, fisetin and quercetin, were
somewhat less efficient in suppressing cellular viability, whereas baicalein,
chrysin, (+)-catechin and hesperetin exerted only a small or no response at doses
as high as 100 MUM. Both fisetin and quercetin were able to augment the cytotoxic
activity of luteolin in both cell lines by reducing the IC50 values up to four
fold. As a result of this, luteolin displayed cytotoxicity activity already at
low micromolar concentrations that could potentially be physiologically
achievable through oral ingestion. No other tested flavonoids were capable of
sensitizing CLL cells to luteolin pointing to a specific binding of fisetin and
quercetin to the cellular targets which interfere with the signaling pathways
induced by luteolin. Although further molecular studies to unravel this
potentiating mechanism are certainly needed, this phenomenon could contribute to
future remedies for prevention and treatment of chronic lymphocytic leukemia.
PMID- 27489196
TI - Current-induced alternating reversed dual-echo-steady-state for joint estimation
of tissue relaxation and electrical properties.
AB - PURPOSE: To develop a current-induced, alternating reversed dual-echo-steady
state-based magnetic resonance electrical impedance tomography for joint
estimation of tissue relaxation and electrical properties. METHODS: The proposed
method reverses the readout gradient configuration of conventional, in which
steady-state-free-precession (SSFP)-ECHO is produced earlier than SSFP-free
induction-decay (FID) while alternating current pulses are applied in between the
two SSFPs to secure high sensitivity of SSFP-FID to injection current.
Additionally, alternating reversed dual-echo-steady-state signals are modulated
by employing variable flip angles over two orthogonal injections of current
pulses. Ratiometric signal models are analytically constructed, from which T1 ,
T2 , and current-induced Bz are jointly estimated by solving a nonlinear inverse
problem for conductivity reconstruction. Numerical simulations and experimental
studies are performed to investigate the feasibility of the proposed method in
estimating relaxation parameters and conductivity. RESULTS: The proposed method,
if compared with conventional magnetic resonance electrical impedance tomography,
enables rapid data acquisition and simultaneous estimation of T1 , T2 , and
current-induced Bz , yielding a comparable level of signal-to-noise ratio in the
parameter estimates while retaining a relative conductivity contrast. CONCLUSION:
We successfully demonstrated the feasibility of the proposed method in jointly
estimating tissue relaxation parameters as well as conductivity distributions. It
can be a promising, rapid imaging strategy for quantitative conductivity
estimation. Magn Reson Med 78:107-120, 2017. (c) 2016 International Society for
Magnetic Resonance in Medicine.
PMID- 27489197
TI - Letter to the Editor: On the Growth of Hematopoietic Stem Cells and Childhood
Leukemias.
PMID- 27489198
TI - Interplay between aggression, brain monoamines and fur color mutation in the
American mink.
AB - Domestication of wild animals alters the aggression towards humans, brain
monoamines and coat pigmentation. Our aim is the interplay between aggression,
brain monoamines and depigmentation. The Hedlund white mutation in the American
mink is an extreme case of depigmentation observed in domesticated animals. The
aggressive (-2.06 +/- 0.03) and tame (+3.5 +/- 0.1) populations of wild-type dark
brown color (standard) minks were bred during 17 successive generations for
aggressive or tame reaction towards humans, respectively. The Hedlund mutation
was transferred to the aggressive and tame backgrounds to generate aggressive (
1.2 +/- 0.1) and tame (+3.0 +/- 0.2) Hedlund minks. Four groups of 10 males with
equal expression of aggressive (-2) or tame (+5) behavior, standard or with the
Hedlund mutation, were selected to study biogenic amines in the brain. Decreased
levels of noradrenaline in the hypothalamus, but increased concentrations of the
serotonin metabolite, 5-hydroxyindoleacetic acid and dopamine metabolite,
homovanillic acid, in the striatum were measured in the tame compared with the
aggressive standard minks. The Hedlund mutation increased noradrenaline level in
the hypothalamus and substantia nigra, serotonin level in the substantia nigra
and striatum and decreased dopamine concentration in the hypothalamus and
striatum. Significant interaction effects were found between the Hedlund mutation
and aggressive behavior on serotonin metabolism in the substantia nigra (P <
0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the
striatum (P < 0.05). These results provide the first experimental evidence of the
interplay between aggression, brain monoamines and the Hedlund mutation in the
American minks.
PMID- 27489199
TI - Is There a Free Lunch in Inference?
AB - The field of psychology, including cognitive science, is vexed by a crisis of
confidence. Although the causes and solutions are varied, we focus here on a
common logical problem in inference. The default mode of inference is
significance testing, which has a free lunch property where researchers need not
make detailed assumptions about the alternative to test the null hypothesis. We
present the argument that there is no free lunch; that is, valid testing requires
that researchers test the null against a well-specified alternative. We show how
this requirement follows from the basic tenets of conventional and Bayesian
probability. Moreover, we show in both the conventional and Bayesian framework
that not specifying the alternative may lead to rejections of the null hypothesis
with scant evidence. We review both frequentist and Bayesian approaches to
specifying alternatives, and we show how such specifications improve inference.
The field of cognitive science will benefit because consideration of reasonable
alternatives will undoubtedly sharpen the intellectual underpinnings of research.
PMID- 27489200
TI - Exploring Human Cognition Using Large Image Databases.
AB - Most cognitive psychology experiments evaluate models of human cognition using a
relatively small, well-controlled set of stimuli. This approach stands in
contrast to current work in neuroscience, perception, and computer vision, which
have begun to focus on using large databases of natural images. We argue that
natural images provide a powerful tool for characterizing the statistical
environment in which people operate, for better evaluating psychological
theories, and for bringing the insights of cognitive science closer to real
applications. We discuss how some of the challenges of using natural images as
stimuli in experiments can be addressed through increased sample sizes, using
representations from computer vision, and developing new experimental methods.
Finally, we illustrate these points by summarizing recent work using large image
databases to explore questions about human cognition in four different domains:
modeling subjective randomness, defining a quantitative measure of
representativeness, identifying prior knowledge used in word learning, and
determining the structure of natural categories.
PMID- 27489201
TI - Corrigendum for: The Ethics of Belief, Cognition, and Climate Change
Pseudoskepticism: Implications for Public Discourse, by Lawrence Torcello in
TopiCS in Cognitive Science, 8(1).
PMID- 27489202
TI - Five-day study to judge the short-term effect of a benzoyl peroxide 3% gel on
acne lesions.
AB - INTRODUCTION: Acne is a common, chronic skin disease that has both physical and
psychological consequences. Over-the-counter products are a treatment option
frequently chosen by dermatologists and acne sufferers for reasons of cost or
convenience. There are reports that such products can effect rapid resolution in
certain lesion parameters. AIMS: To evaluate the short-term effect of a benzoyl
peroxide 3% gel on acne lesions. METHODS: A 5-day, double-blind, randomized
clinical trial was conducted among subjects with mild-to-moderate acne. Subjects
applied the benzoyl peroxide 3% gel, a salicylic acid 2% gel, or a vehicle gel
under supervision once daily for 4 days. Target lesion parameters of swelling,
diameter, and erythema were evaluated at various times after the first and
subsequent applications. RESULTS: Although target lesion parameters showed
overall improvement from baseline, the effects of the active treatment gels were
not significantly different from those of the vehicle gel at any evaluation. The
assessed parameters showed marked variability in target lesion behavior at the
subject level over the course of the study. CONCLUSIONS: The results of this
study illustrate the unpredictability of individual acne lesion's responses to
therapy and the challenge associated with using these responses to judge short
term treatment efficacy. While rapid acne resolution is desired by patients and
consumers, setting realistic expectations for treatment response is critical to
encourage compliance and avoid disappointment.
PMID- 27489203
TI - Combined use of ionic liquid and sulfobutylether-beta-cyclodextrin as electrolyte
additives for separation and determination of camptothecin alkaloids by CZE.
AB - This work reported that ionic liquid (IL) ([Bmim] [PF6 ]) and sulfobutylether
beta-CD (SBE-beta-CD) were used as electrolyte additives for the separation and
determination of camptothecin (CPT) alkaloids by CZE. Separation parameters such
as the buffer type, pH, and concentration of the running buffer, the
concentration of SBE-beta-CD and IL, temperature, and separation voltage were all
investigated in order to achieve the maximum possible resolution. The four
analytes were baseline separated within 10 min in capillary at the separation
voltage of 15 kV with a running buffer consisting of 20 mM borate buffer, 20 mM
IL, and 100 mM SBE-beta-CD at pH 9.0. Under such conditions, good linearity about
two orders of magnitudes of peak areas was achieved for the investigated CPT
alkaloids with the correlation coefficients ranging from 0.9946 to 0.9985. For
all analytes, detection limits (S/N = 3) and quantitation limits (S/N = 10) range
from 0.05 to 0.92 MUg/mL and 0.17 to 3.06 MUg/mL, respectively. The proposed
method has not only been successfully applied to the separation and determination
of CPT alkaloids but also showed that IL seemed to be a promising additive in CZE
separation.
PMID- 27489204
TI - Home-Based Psychiatric Outpatient Care Through Videoconferencing for Depression:
A Randomized Controlled Follow-Up Trial.
AB - BACKGROUND: There is a tremendous opportunity for innovative mental health care
solutions such as psychiatric care through videoconferencing to increase the
number of people who have access to quality care. However, studies are needed to
generate empirical evidence on the use of psychiatric outpatient care via
videoconferencing, particularly in low- and middle-income countries and
clinically unsupervised settings. OBJECTIVE: The objective of this study was to
evaluate the effectiveness and feasibility of home-based treatment for mild
depression through psychiatric consultations via videoconferencing. METHODS: A
randomized controlled trial with a 6- and 12-month follow-up including adults
with mild depression treated in an ambulatory setting was conducted. In total,
107 participants were randomly allocated to the videoconferencing intervention
group (n=53) or the face-to-face group (F2F; n=54). The groups did not differ
with respect to demographic characteristics at baseline. The F2F group completed
monthly follow-up consultations in person. The videoconferencing group received
monthly follow-up consultations with a psychiatrist through videoconferencing at
home. At baseline and after 6 and 12 months, in-person assessments were conducted
with all participants. Clinical outcomes (severity of depression, mental health
status, medication course, and relapses), satisfaction with treatment,
therapeutic relationship, treatment adherence (appointment compliance and
dropouts), and medication adherence were assessed. RESULTS: The severity of
depression decreased significantly over the 12-month follow-up in both the
groups. There was a significant difference between groups regarding treatment
outcomes throughout the follow-up period, with better results in the
videoconferencing group. There were 4 relapses in the F2F group and only 1 in the
videoconferencing group. No significant differences between groups regarding
mental health status, satisfaction with treatment, therapeutic relationship,
treatment adherence, or medication compliance were found. However, after 6
months, the rate of dropouts was significantly higher in the F2F group (18.5% vs
5.7% in the videoconferencing group, P<.05). CONCLUSIONS: Psychiatric treatment
through videoconferencing in clinically unsupervised settings can be considered
feasible and as effective as standard care (in-person treatment) for depressed
outpatients with respect to clinical outcomes, patient satisfaction, therapeutic
relationship, treatment adherence, and medication compliance. These results
indicate the potential of telepsychiatry to extend access to psychiatric care to
remote and underserved populations. CLINICALTRIAL: Clinicaltrials.gov
NCT01901315; https://clinicaltrials.gov/ct2/show/NCT01901315 (Archived by WebCite
at http://www.webcitation.org/6jBTrIVwg).
PMID- 27489205
TI - ART is an alternative for restoring occlusoproximal cavities in primary teeth -
evidence from an updated systematic review and meta-analysis.
AB - BACKGROUND: A previous systematic review showed that atraumatic restorative
treatment (ART) can be an option to restore the occlusoproximal cavities in
primary teeth; however, few studies fulfilled the criteria of inclusion to
generate a high level of evidence. AIM: To update the existing systematic review
and address questions regarding survival rate of ART restorations compared to the
conventional approach in occlusoproximal cavities in primary molars. DESIGN: The
search was extended beyond the original search through the PubMed/MEDLINE
database up to February 2016. Furthermore, Web of Science and EMBASE were
searched. The inclusion criteria were subjects related to the scope of the
systematic review. After selection by title and abstract, potentially eligible
articles were read in full and included in accordance with exclusion criteria.
Meta-analysis was carried out with the outcome being the survival rate of
restorations. RESULTS: The search strategy identified 560 potentially relevant
studies, in addition to 127 from the original systematic review. A total of four
articles were included in the qualitative and quantitative analyses. Meta
analysis showed no statistically significant difference between ART and
conventional approaches in survival rate of occlusoproximal cavities (OR = 0.887,
95% CI: 0.574-1.371). CONCLUSION: ART restorations have similar survival rate
compared to conventional treatment and can be considered an option to restore
occlusoproximal cavities in primary molars.
PMID- 27489206
TI - Mapping the patent landscape of synthetic biology for fine chemical production
pathways.
AB - A goal of synthetic biology bio-foundries is to innovate through an iterative
design/build/test/learn pipeline. In assessing the value of new chemical
production routes, the intellectual property (IP) novelty of the pathway is
important. Exploratory studies can be carried using knowledge of the patent/IP
landscape for synthetic biology and metabolic engineering. In this paper, we
perform an assessment of pathways as potential targets for chemical production
across the full catalogue of reachable chemicals in the extended metabolic space
of chassis organisms, as computed by the retrosynthesis-based algorithm
RetroPath. Our database for reactions processed by sequences in heterologous
pathways was screened against the PatSeq database, a comprehensive collection of
more than 150M sequences present in patent grants and applications. We also
examine related patent families using Derwent Innovations. This large-scale
computational study provides useful insights into the IP landscape of synthetic
biology for fine and specialty chemicals production.
PMID- 27489207
TI - Genome-Wide Analysis of Polyadenylation Events in Schmidtea mediterranea.
AB - In eukaryotes, 3' untranslated regions (UTRs) play important roles in regulating
posttranscriptional gene expression. The 3'UTR is defined by regulated
cleavage/polyadenylation of the pre-mRNA. The advent of next-generation
sequencing technology has now enabled us to identify these events on a genome
wide scale. In this study, we used poly(A)-position profiling by sequencing (3P
Seq) to capture all poly(A) sites across the genome of the freshwater planarian,
Schmidtea mediterranea, an ideal model system for exploring the process of
regeneration and stem cell function. We identified the 3'UTRs for ~14,000
transcripts and thus improved the existing gene annotations. We found 97
transcripts, which are polyadenylated within an internal exon, resulting in the
shrinking of the ORF and loss of a predicted protein domain. Around 40% of the
transcripts in planaria were alternatively polyadenylated (ApA), resulting either
in an altered 3'UTR or a change in coding sequence. We identified specific ApA
transcript isoforms that were subjected to miRNA mediated gene regulation using
degradome sequencing. In this study, we also confirmed a tissue-specific
expression pattern for alternate polyadenylated transcripts. The insights from
this study highlight the potential role of ApA in regulating the gene expression
essential for planarian regeneration.
PMID- 27489208
TI - Interallelic Transcriptional Enhancement as an in Vivo Measure of Transvection in
Drosophila melanogaster.
AB - Transvection-pairing-dependent interallelic regulation resulting from enhancer
action in trans-occurs throughout the Drosophila melanogaster genome, likely as a
result of the extensive somatic homolog pairing seen in Dipteran species. Recent
studies of transvection in Drosophila have demonstrated important qualitative
differences between enhancer action in cis vs. in trans, as well as a modest
synergistic effect of cis- and trans-acting enhancers on total tissue transcript
levels at a given locus. In the present study, we identify a system in which cis-
and trans-acting GAL4-UAS enhancer synergism has an unexpectedly large
quantitative influence on gene expression, boosting total tissue transcript
levels at least fourfold relative to those seen in the absence of transvection.
We exploit this strong quantitative effect by using publicly available UAS-shRNA
constructs from the TRiP library to assay candidate genes for transvection
activity in vivo The results of the present study, which demonstrate that in
trans activation by simple UAS enhancers can have large quantitative effects on
gene expression in Drosophila, have important new implications for experimental
design utilizing the GAL4-UAS system.
PMID- 27489209
TI - Cross-Validation Without Doing Cross-Validation in Genome-Enabled Prediction.
AB - Cross-validation of methods is an essential component of genome-enabled
prediction of complex traits. We develop formulae for computing the predictions
that would be obtained when one or several cases are removed in the training
process, to become members of testing sets, but by running the model using all
observations only once. Prediction methods to which the developments apply
include least squares, best linear unbiased prediction (BLUP) of markers, or
genomic BLUP, reproducing kernels Hilbert spaces regression with single or
multiple kernel matrices, and any member of a suite of linear regression methods
known as "Bayesian alphabet." The approach used for Bayesian models is based on
importance sampling of posterior draws. Proof of concept is provided by applying
the formulae to a wheat data set representing 599 inbred lines genotyped for 1279
markers, and the target trait was grain yield. The data set was used to evaluate
predictive mean-squared error, impact of alternative layouts on maximum
likelihood estimates of regularization parameters, model complexity, and residual
degrees of freedom stemming from various strengths of regularization, as well as
two forms of importance sampling. Our results will facilitate carrying out
extensive cross-validation without model retraining for most machines employed in
genome-assisted prediction of quantitative traits.
PMID- 27489210
TI - Genome Evolution in Three Species of Cactophilic Drosophila.
AB - We report genomes of two species of cactophilic Drosophila: Drosophila arizonae
and D. navojoa These two are the closest relatives of D. mojavensis, forming the
D. mojavensis cluster. D. mojavensis and D. arizonae diverged from D. navojoa
~5.8 Mya, while the split between D. arizonae and D. mojavensis is more recent,
at 1.5 Mya. Together the three genomes provide opportunities to examine genomic
changes associated with speciation and host shifts in this ecologically defined
group of flies. The three species are also separated by fixed inversion
differences in three of their six chromosomes. While the levels of nucleotide
divergence in the colinear chromosomes are significantly lower than in the
inverted chromosomes, consistent with a past role of the inversions in preventing
gene flow, the patterns differ among the inverted chromosomes when the locations
of nucleotides inside or outside of the inversions are considered. For Muller
element E, there is greater divergence external to the inversion breakpoints. For
Muller A, the divergence is slightly higher inside the inversions, while for
Muller B, the breakpoints and hence the difference in substitutions in relation
to the inversions could not be determined. The differences among the inverted
chromosomes, especially once the breakpoints are clearly established, could aid
in dating the origins of the inversions.
PMID- 27489212
TI - Preferential intracellular pH regulation: hypotheses and perspectives.
AB - The regulation of vertebrate acid-base balance during acute episodes of elevated
internal PCO2 is typically characterized by extracellular pH (pHe) regulation.
Changes in pHe are associated with qualitatively similar changes in intracellular
tissue pH (pHi) as the two are typically coupled, referred to as 'coupled pH
regulation'. However, not all vertebrates rely on coupled pH regulation; instead,
some preferentially regulate pHi against severe and maintained reductions in pHe
Preferential pHi regulation has been identified in several adult fish species and
an aquatic amphibian, but never in adult amniotes. Recently, common snapping
turtles were observed to preferentially regulate pHi during development; the
pattern of acid-base regulation in these species shifts from preferential pHi
regulation in embryos to coupled pH regulation in adults. In this Commentary, we
discuss the hypothesis that preferential pHi regulation may be a general strategy
employed by vertebrate embryos in order to maintain acid-base homeostasis during
severe acute acid-base disturbances. In adult vertebrates, the retention or loss
of preferential pHi regulation may depend on selection pressures associated with
the environment inhabited and/or the severity of acid-base regulatory challenges
to which they are exposed. We also consider the idea that the retention of
preferential pHi regulation into adulthood may have been a key event in
vertebrate evolution, with implications for the invasion of freshwater habitats,
the evolution of air breathing and the transition of vertebrates from water to
land.
PMID- 27489211
TI - Assessment of the Pharmacokinetics, Pharmacodynamics, and Safety of Single Doses
of TV-1106, a Long-Acting Growth Hormone, in Healthy Japanese and Caucasian
Subjects.
AB - TV-1106 is a human serum albumin genetically fused to recombinant human growth
hormone, designed to provide a long-acting alternative to daily growth hormone
(GH) injections in patients with GH deficiency. This study investigated the
pharmacokinetics, pharmacodynamics, and safety of single subcutaneous doses of TV
1106 (7.5, 15, 50, and 100 mg) in Japanese (n = 44) and caucasian (n = 44)
healthy subjects. TV-1106 pharmacokinetics and pharmacodynamics were comparable
in Japanese and caucasian populations. TV-1106 demonstrated relatively slow
absorption (median tmax , 10-30 hours) and a mean elimination half-life of 26-36
hours. Apparent clearance and volume of distribution decreased with increasing TV
1106 doses in both populations and appeared to increase more than dose
proportionality across the tested doses. Insulin-like growth factor-1 (IGF-1) and
IGF binding protein-3 (IGFBP-3) increased in a dose-related manner, with maximum
responses observed at 33-96 and 42-109 hours, respectively. IGF-1 and IGFBP-3
returned to baseline values at 168 hours following 7.5 and 15 mg of TV-1106, and
336 hours following 50 and 100 mg of TV-1106. TV-1106 appeared safe in both
populations. There was no evidence of differences in pharmacokinetics,
pharmacodynamics, or safety of TV-1106 between Japanese and caucasian
populations. The data also demonstrate long-acting growth hormone properties of
TV-1106 and support its potential for once-weekly dosing.
PMID- 27489213
TI - Amphibious fishes: evolution and phenotypic plasticity.
AB - Amphibious fishes spend part of their life in terrestrial habitats. The ability
to tolerate life on land has evolved independently many times, with more than 200
extant species of amphibious fishes spanning 17 orders now reported. Many
adaptations for life out of water have been described in the literature, and
adaptive phenotypic plasticity may play an equally important role in promoting
favourable matches between the terrestrial habitat and behavioural,
physiological, biochemical and morphological characteristics. Amphibious fishes
living at the interface of two very different environments must respond to issues
relating to buoyancy/gravity, hydration/desiccation, low/high O2 availability,
low/high CO2 accumulation and high/low NH3 solubility each time they traverse the
air-water interface. Here, we review the literature for examples of plastic
traits associated with the response to each of these challenges. Because there is
evidence that phenotypic plasticity can facilitate the evolution of fixed traits
in general, we summarize the types of investigations needed to more fully
determine whether plasticity in extant amphibious fishes can provide indications
of the strategies used during the evolution of terrestriality in tetrapods.
PMID- 27489214
TI - The high cost of reproduction in sea otters necessitates unique physiological
adaptations.
AB - Superimposed on inherently high basal metabolic demands, the additional energetic
requirements of reproduction can push female sea otters beyond physiological
limits. Indeed, the resulting energy imbalance contributes to disproportionately
high rates of mortality at the end of lactation in this species. To examine and
quantify metabolic changes associated with reproduction, we measured the resting
metabolic rate (RMR) of a female sea otter across gestation, lactation and non
reproductive periods. Concurrently, measurements were made on a non-breeding
control female. Our results suggest that RMR declines during gestation.
Conversely, RMR increases during lactation, reaches a peak at 3-4 months
postpartum, and remains elevated until weaning. Combining these direct
measurements with published data, we found the cost of pup rearing to be
significantly higher than previously estimated. High baseline energy demands and
limited energy reserves, combined with significant lactation and pup rearing
costs, appear to necessitate metabolic and thermal lability during key
reproductive stages.
PMID- 27489215
TI - Repair of traumatized mammalian hair cells via sea anemone repair proteins.
AB - Mammalian hair cells possess only a limited ability to repair damage after
trauma. In contrast, sea anemones show a marked capability to repair damaged hair
bundles by means of secreted repair proteins (RPs). Previously, it was found that
recovery of traumatized hair cells in blind cavefish was enhanced by anemone
derived RPs; therefore, the ability of anemone RPs to assist recovery of damaged
hair cells in mammals was tested here. After a 1 h incubation in RP-enriched
culture media, uptake of FM1-43 by experimentally traumatized murine cochlear
hair cells was restored to levels comparable to those exhibited by healthy
controls. In addition, RP-treated explants had significantly more normally
structured hair bundles than time-matched traumatized control explants.
Collectively, these results indicate that anemone-derived RPs assist in restoring
normal function and structure of experimentally traumatized hair cells of the
mouse cochlea.
PMID- 27489216
TI - Ammonia excretion in mytilid mussels is facilitated by ciliary beating.
AB - The excretion of nitrogenous waste products in the form of ammonia (NH3) and
ammonium (NH4 (+)) is a fundamental process in aquatic organisms. For mytilid
bivalves, little is known about the mechanisms and sites of excretion. This study
investigated the localization and the mechanisms of ammonia excretion in mytilid
mussels. An Rh protein was found to be abundantly expressed in the apical cell
membrane of the plicate organ, which was previously described as a solely
respiratory organ. The Rh protein was also expressed in the gill, although at
significantly lower concentrations, but was not detectable in mussel kidney.
Furthermore, NH3/NH4 (+) was not enriched in the urine, suggesting that kidneys
are not involved in active NH3/NH4 (+) excretion. Exposure to elevated seawater
pH of 8.5 transiently reduced NH3/NH4 (+) excretion rates, but they returned to
control values following 24 h acclimation. These mussels had increased abundance
of V-type H(+)-ATPase in the apical membranes of plicate organ cells; however,
NH3/NH4 (+) excretion rates were not affected by the V-type H(+)-ATPase specific
inhibitor concanamycin A (100 nmol l(-1)). In contrast, inhibition of ciliary
beating with dopamine and increased seawater viscosity significantly reduced NH3
excretion rates under control pH (8.0). These results suggest that NH3/NH4 (+)
excretion in mytilid mussels takes place by passive NH3 diffusion across
respiratory epithelia via the Rh protein, facilitated by the water current
produced for filter feeding, which prevents accumulation of NH3 in the boundary
layer. This mechanism would be energy efficient for sessile organisms, as they
already generate water currents for filter feeding.
PMID- 27489217
TI - Intermuscular pressure between synergistic muscles correlates with muscle force.
AB - The purpose of the study was to examine the relationship between muscle force
generated during isometric contractions (i.e. at a constant muscle-tendon unit
length) and the intermuscular (between adjacent muscles) pressure in synergistic
muscles. Therefore, the pressure at the contact area of the gastrocnemius and
plantaris muscle was measured synchronously to the force of the whole calf
musculature in the rabbit species Oryctolagus cuniculus Similar results were
obtained when using a conductive pressure sensor, or a fibre-optic pressure
transducer connected to a water-filled balloon. Both methods revealed a strong
linear relationship between force and pressure in the ascending limb of the force
length relationship. The shape of the measured force-time and pressure-time
traces was almost identical for each contraction (r=0.97). Intermuscular pressure
ranged between 100 and 700 mbar (70,000 Pa) for forces up to 287 N. These
pressures are similar to previous (intramuscular) recordings within skeletal
muscles of different vertebrate species. Furthermore, our results suggest that
the rise in intermuscular pressure during contraction may reduce the force
production in muscle packages (compartments).
PMID- 27489218
TI - Arginine and proline applied as food additives stimulate high freeze tolerance in
larvae of Drosophila melanogaster.
AB - The fruit fly Drosophila melanogaster is an insect of tropical origin. Its larval
stage is evolutionarily adapted for rapid growth and development under warm
conditions and shows high sensitivity to cold. In this study, we further
developed an optimal acclimation and freezing protocol that significantly
improves larval freeze tolerance (an ability to survive at -5 degrees C when most
of the freezable fraction of water is converted to ice). Using the optimal
protocol, freeze survival to adult stage increased from 0.7% to 12.6% in the
larvae fed standard diet (agar, sugar, yeast, cornmeal). Next, we fed the larvae
diets augmented with 31 different amino compounds, administered in different
concentrations, and observed their effects on larval metabolomic composition,
viability, rate of development and freeze tolerance. While some diet additives
were toxic, others showed positive effects on freeze tolerance. Statistical
correlation revealed tight association between high freeze tolerance and high
levels of amino compounds involved in arginine and proline metabolism. Proline-
and arginine-augmented diets showed the highest potential, improving freeze
survival to 42.1% and 50.6%, respectively. Two plausible mechanisms by which high
concentrations of proline and arginine might stimulate high freeze tolerance are
discussed: (i) proline, probably in combination with trehalose, could reduce
partial unfolding of proteins and prevent membrane fusions in the larvae exposed
to thermal stress (prior to freezing) or during freeze dehydration; (ii) both
arginine and proline are exceptional among amino compounds in their ability to
form supramolecular aggregates which probably bind partially unfolded proteins
and inhibit their aggregation under increasing freeze dehydration.
PMID- 27489219
TI - P450 aromatase: a key enzyme in the spermatogenesis of the Italian wall lizard,
Podarcis sicula.
AB - P450 aromatase is a key enzyme in steroidogenesis involved in the conversion of
testosterone into 17beta-estradiol. We investigated the localization and the
expression of P450 aromatase in Podarcis sicula testes during the different
phases of the reproductive cycle: summer stasis (July-August), early autumnal
resumption (September), middle autumnal resumption (October-November), winter
stasis (December-February), spring resumption (March-April) and the reproductive
period (May-June). Using immunohistochemistry, we demonstrated that the P450
aromatase is always present in somatic and germ cells of P. sicula testis,
particularly in spermatids and spermatozoa, except in early autumnal resumption,
when P450 aromatase is evident only within Leydig cells. Using real-time PCR and
semi-quantitative blot investigations, we also demonstrated that both mRNA and
protein were expressed in all phases, with two peaks of expression occurring in
summer and in winter stasis. These highest levels of P450 aromatase are in line
with the increase of 17beta-estradiol, responsible for the spermatogenesis block
typical of this species. Differently, in autumnal resumption, the level of P450
aromatase dramatically decreased, along with 17beta-estradiol levels, and
testosterone titres increased, responsible for the subsequent renewal of
spermatogenesis not followed by spermiation. In spring resumption and in the
reproductive period we found intermediate P450 aromatase amounts, low levels of
17beta-estradiol and the highest testosterone levels determining the resumption
of spermatogenesis needed for reproduction. Our results, the first collected in a
non-mammalian vertebrate, indicate a role of P450 aromatase in the control of
steroidogenesis and spermatogenesis, particularly in spermiogenesis.
PMID- 27489220
TI - Avian thermoregulation in the heat: evaporative cooling capacity in an archetypal
desert specialist, Burchell's sandgrouse (Pterocles burchelli).
PMID- 27489221
TI - Geriatric problems correlated with cognitive decline using a screening test named
"Dr. SUPERMAN" for comprehensive geriatric assessment in elderly inpatients.
AB - AIM: We have recently developed and validated a screening test for comprehensive
geriatric assessment (CGA). We investigated the prevalence of geriatric problems
in elderly inpatients using CGA, and determined the relationship between
geriatric problems and cognitive decline. METHODS: We enrolled consecutive
elderly inpatients aged >65 years who were admitted to all of the hospital
departments at Tokyo Medical University Hospital, Tokyo, Japan, between July and
December 2013. We investigated the prevalence of specific geriatric problems or
situations in elderly inpatients using a screening test for CGA named "Dr.
SUPERMAN." We examined 3969 elderly inpatients (2211 men and 1758 women; mean age
75.5 +/- 6.7 years) using CGA. Inpatients were divided into three groups by age,
namely, 65-74 years, 75-84 years and >=85 years. Inpatients were divided into the
two groups of "internal medicine" and "other departments." RESULTS: Geriatric
problems were more frequently found in patients who were aged >=85 years and
admitted to "internal medicine" departments. Furthermore, multiple regression
analysis found cognitive decline significantly correlated with ADL decline, age,
poor medication adherence, upper and lower extremity function disorder,
visual/auditory disorder, and urinary disorder. In particular, cognitive decline
strongly correlated with a decline in activities of daily living. CONCLUSIONS:
CGA should be considered for the treatment of elderly inpatients, particularly
those with cognitive decline and admitted to "internal medicine" departments.
Geriatr Gerontol Int 2017; 17: 1252-1256.
PMID- 27489222
TI - Normalising and planning for death in residential care: findings from a
qualitative focus group study of a specialist palliative care intervention.
AB - BACKGROUND: Improving access to palliative care for older adults living in
residential care is recognised internationally as a pressing clinical need. The
integration of specialist palliative care in residential care for older adults is
not yet standard practice. OBJECTIVE: This study aimed to understand the
experience and impact of integrating a specialist palliative care model on
residents, relatives and staff. METHODS: Focus groups were held with staff (n=40)
and relatives (n=17). Thematic analysis was applied to the data. RESULTS: Three
major themes were identified. The intervention led to (1) normalising death and
dying in these settings, (2) timely access to a palliative care specialist who
was able to prescribe anticipatory medications aiding symptom management and
unnecessary hospitalisations and (3) better decision-making and planned care for
residents, which meant that staff and relatives were better informed about, and
prepared for, the resident's likely trajectory. CONCLUSIONS: The intervention
normalised death and dying and also underlined the important role that
specialists play in providing staff education, timely access to medicines and
advance care planning. The findings from our study, and the growing wealth of
evidence integrating specialist palliative care in residential care for older
adults, indicate a number of priorities for care providers, academics and
policymakers. Further work on determining the role of primary and specialist
palliative care services in residential care settings is needed to inform service
delivery models.
PMID- 27489223
TI - Ghrelin O-acyltransferase (GOAT), a specific enzyme that modifies ghrelin with a
medium-chain fatty acid.
AB - In the gastric peptide hormone ghrelin, serine 3 (threonine 3 in frogs) is
modified, primarily by n-octanoic acid; this modification is essential for
ghrelin's activity. The enzyme that transfers n-octanoic acid to Ser3 of ghrelin
is ghrelin O-acyltransferase (GOAT). GOAT, the only enzyme known to catalyze acyl
modification of ghrelin, specifically modifies serine (or threonine) at the third
position and does not modify other serine residues in ghrelin peptides. GOAT
prefers n-hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the
stomach the n-octanoyl form is the predominant form of acyl-modified ghrelin.
GOAT is a promising target for drug development to treat metabolic diseases and
eating disorders.
PMID- 27489224
TI - Simulating the slow to fast switch in cytochrome c oxidase catalysis by
introducing a loop flip near the enzyme's cytochrome c (substrate) binding site.
AB - The mitochondrial enzyme cytochrome c oxidase catalyzes the reduction of
molecular oxygen in the critical step of oxidative phosphorylation that links the
oxidation of food consumed to ATP production in cells. The enzyme catalyzes the
reduction of oxygen at two vastly different rates that are thought to be linked
to two different conformations but the conformation of the "fast enzyme" remains
obscure. In this study, we demonstrated how oxygen binding at haem a3 could
trigger long-distance conformational changes and then simulated a conformational
change in an eight-residue loop near the enzyme's substrate (cytochrome c)
binding site. We then used this modified cytochrome c oxidase (COX) to simulate a
stable COX-cytochrome c enzyme-substrate (ES) complex. Compared to ES complexes
formed in the absence of the conformation change, the distance between the redox
centers of the two proteins was reduced by half and instead of nine, only four
COX amino acid residues were found along the axis linking the electron entry
point and the CuA redox center of COX: We proposed that intramolecular electron
transfer in COX occurs via a charge/hydrogen relay system involving these four
residues. We suggest that the conformational change and resulting shortened
electron pathway are features of fast-acting COX.
PMID- 27489225
TI - The intervertebral disc contains intrinsic circadian clocks that are regulated by
age and cytokines and linked to degeneration.
AB - OBJECTIVES: The circadian clocks are internal timing mechanisms that drive ~24
hour rhythms in a tissue-specific manner. Many aspects of the physiology of the
intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown
whether IVD tissue contains functional circadian clocks and if so, how their
dysregulation is implicated in IVD degeneration. METHODS: Clock gene dynamics in
ex vivo IVD explants (from PER2:: luciferase (LUC) reporter mice) and human disc
cells (transduced with lentivirus containing Per2::luc reporters) were monitored
in real time by bioluminescence photon counting and imaging. Temporal gene
expression changes were studied by RNAseq and quantitative reverse transcription
(qRT)-PCR. IVD pathology was evaluated by histology in a mouse model with tissue
specific deletion of the core clock gene Bmal1. RESULTS: Here we show the
existence of the circadian rhythm in mouse IVD tissue and human disc cells. This
rhythm is dampened with ageing in mice and can be abolished by treatment with
interleukin-1beta but not tumour necrosis factor alpha. Time-series RNAseq
revealed 607 genes with 24-hour patterns of expression representing several
essential pathways in IVD physiology. Mice with conditional knockout of Bmal1 in
their disc cells demonstrated age-related degeneration of IVDs. CONCLUSIONS: We
have established autonomous circadian clocks in mouse and human IVD cells which
respond to age and cytokines, and control key pathways involved in the
homeostasis of IVDs. Genetic disruption to the mouse IVD molecular clock
predisposes to IVD degeneration. These results support the concept that
disruptions to circadian rhythms may be a risk factor for degenerative IVD
disease and low back pain.
PMID- 27489227
TI - Cultivating Resilience in Families Who Foster: Understanding How Families Cope
and Adapt Over Time.
AB - Families who foster offer essential care for children and youth when their own
parents are unable to provide for their safety and well-being. Foster caregivers
face many challenges including increased workload, emotional distress, and the
difficulties associated with health and mental health problems that are more
common in children in foster care. Despite these stressors, many families are
able to sustain fostering while maintaining or enhancing functioning of their
unit. This qualitative study applied an adaptational process model of family
resilience that emerged in previous studies to examine narratives of persistent,
long-term, and multiple fostering experiences. Data corroborated previous
research in two ways. Family resilience was again described as a transactional
process of coping and adaptation that evolves over time. This process was
cultivated through the activation of 10 family strengths that are important in
different ways, during varied phases.
PMID- 27489226
TI - Response to: 'The role of infrapatellar fat pad resection in total knee
arthroplasty' by White et al.
PMID- 27489228
TI - A cost-effectiveness analysis of optimal care for diabetic foot ulcers in
Australia.
AB - In addition to affecting quality of life, diabetic foot ulcers (DFUs) impose an
economic burden on both patients and the health system. This study developed a
Markov model to analyse the cost-effectiveness of implementing optimal care in
comparison with the continuation of usual care for diabetic patients at high risk
of DFUs in the Australian setting. The model results demonstrated overall 5-year
cost savings (AUD 9100.11 for those aged 35-54, $9391.60 for those aged 55-74 and
$12 394.97 for those aged 75 or older) and improved health benefits measured in
quality-adjusted life years (QALYs) (0.13 QALYs, 0.13 QALYs and 0.16 QALYs,
respectively) for high-risk patients receiving optimal care for DFUs compared
with usual care. Total cost savings for Australia were estimated at AUD 2.7
billion over 5 years. Probabilistic sensitivity analysis showed that optimal care
always had a higher probability of costing less and generating more health
benefits. This study provides important evidence to inform Australian policy
decisions on the efficient use of health resources and supports the
implementation of evidence-based optimal care in Australia. Furthermore, this
information is of great importance for comparable developed countries that could
reap similar benefits from investing in these well-known evidence-based
strategies.
PMID- 27489229
TI - Response: Commentary: Enhanced Monitoring of the Preterm Infant during
Stabilization in the Delivery Room.
PMID- 27489230
TI - Development of a neurofeedback protocol targeting the frontal pole using near
infrared spectroscopy.
AB - AIM: Neurofeedback has been studied with the aim of controlling cerebral
activity. Near-infrared spectroscopy is a non-invasive neuroimaging technique
used for measuring hemoglobin concentration changes in cortical surface areas
with high temporal resolution. Thus, near-infrared spectroscopy may be useful for
neurofeedback, which requires real-time feedback of repeated brain activation
measurements. However, no study has specifically targeted neurofeedback, using
near-infrared spectroscopy, in the frontal pole cortex. METHODS: We developed an
original near-infrared spectroscopy neurofeedback system targeting the frontal
pole cortex. Over a single day of testing, each healthy participant (n = 24)
received either correct or incorrect (Sham) feedback from near-infrared
spectroscopy signals, based on a crossover design. RESULTS: Under correct
feedback conditions, significant activation was observed in the frontal pole
cortex (P = 0.000073). Additionally, self-evaluation of control and metacognitive
beliefs were associated with near-infrared spectroscopy signals (P = 0.006).
CONCLUSION: The neurofeedback system developed in this study might be useful for
developing control of frontal pole cortex activation.
PMID- 27489231
TI - Obovatol Induces Apoptosis in Non-small Cell Lung Cancer Cells via C/EBP
Homologous Protein Activation.
AB - Although obovatol, a phenolic compound from the bark of Magnolia obovata, was
known to have antioxidant, neuroprotective, antiinflammatory, antithrombotic and
antitumour effects, its underlying antitumour mechanism is poorly understood so
far. Thus, in the present study, the antitumour molecular mechanism of obovatol
was investigated in non-small cell lung cancer cells (NSCLCs). Obovatol exerted
cytotoxicity in A549 and H460 NSCLCs, but not in BEAS-2B cells. Also, obovatol
increased sub-G1 accumulation and early and late apoptotic portion in A549 and
H460 NSCLCs. Consistently, obovatol cleaved PARP, activated caspase 9/3 and Bax
and attenuated the expression of cyclin D1 in A549 and H460 NSCLCs.
Interestingly, obovatol upregulated the expression of endoplasmic reticulum
stress proteins such as C/EBP homologous protein (CHOP), IRE1alpha, ATF4 and p
elF2 in A549 and H460 NSCLCs. Conversely, depletion of CHOP blocked the apoptotic
activity of obovatol to increase sub-G1 accumulation in A549 and H460 NSCLCs.
Overall, our findings support scientific evidences that obovatol induces
apoptosis via CHOP activation in A549 and H460 NSCLCs. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27489232
TI - Exercise From the Perspective of Iranian Traditional Medicine.
AB - Exercise, in Iranian traditional medicine, is 1 of the 6 principles recommended
for maintaining good health. There are some considerations that must be taken
into account before, during, and after exercise. Exercise has different terms in
different individuals, seasons, and ages. According to these principles, the
interval between exercise and eating food is very important. Exercise after
eating is inappropriate, and it is recommended that the best time for exercise is
after food has been completely digested and before the next meal. According to
the opinion of traditional medicine philosophers, exercise should be done after
the complete digestion of food. Exercise may be more effective if it is done
according to traditional medicine view at appropriate times and conditions with
sufficient intensity and duration.
PMID- 27489233
TI - Mindfulness-Based Stress Reduction as a Stress Management Intervention for Cancer
Care: A Systematic Review.
AB - Cancer is acknowledged as a source of stress for many individuals, often leading
to suffering, which can be long-lasting. Mindfulness-based stress reduction
offers an effective way of reducing stress among cancer patients by combining
mindfulness meditation and yoga in an 8-week training program. The purpose of
this study was to inspect studies from October 2009 to November 2015 and examine
whether mindfulness-based stress reduction can be utilized as a viable method for
managing stress among cancer patients. A systematic search from Medline, CINAHL,
and Alt HealthWatch databases was conducted for quantitative articles involving
mindfulness-based stress reduction interventions targeting cancer patients. A
total of 13 articles met the inclusion criteria. Of these 13 studies, 9
demonstrated positive changes in either psychological or physiological outcomes
related to anxiety and/or stress, with 4 describing mixed results. Despite the
limitations, mindfulness-based stress reduction appears to be promising for
stress management among cancer patients.
PMID- 27489234
TI - Legionella saoudiensis sp. nov., isolated from a sewage water sample.
AB - A Gram-stain-negative, bacilli-shaped bacterial strain, LS-1T, was isolated from
a sewage water sample collected in Jeddah, Saudi Arabia. The taxonomic position
of strain LS-1T was investigated using a polyphasic taxonomic approach.
Phylogenetic analysis based on 16S rRNA gene sequences and those of four other
genes indicated that strain LS-1T belongs to the genus Legionella in the family
Legionellaceae. Regarding the 16S rRNA gene, the most closely related species are
Legionella rowbothamii LLAP-6T (98.6 %) and Legionella lytica L2T (98.5 %). The
mip gene sequence of strain LS-1T showed 94 % sequence similarity with that of L.
lytica L2T and 93 % similarity with that of L. rowbothamii LLAP-6T. Strain LS-1T
grew optimally at a temperature of 32 degrees C on a buffered charcoal yeast
extract (BCYE) agar plate in a 5 % CO2 atmosphere and had a flagellum. The
combined phylogenetic, phenotypic and genomic sequence data suggest that strain
LS-1T represents a novel species of the genus Legionella, for which the name
Legionella saoudiensis sp. nov. is proposed. The type strain is LS-1T (=DSM
101682T=CSUR P2101T).
PMID- 27489235
TI - Grain production versus resource and environmental costs: towards increasing
sustainability of nutrient use in China.
AB - Over the past five decades, Chinese grain production has increased 4-fold, from
110 Mt in 1961 to 557 Mt in 2014, with less than 9% of the world's arable land
feeding 22% of the world's population, indicating a substantial contribution to
global food security. However, compared with developed economies, such as the USA
and the European Union, more than half of the increased crop production in China
can be attributed to a rapid increase in the consumption of chemicals,
particularly fertilizers. Excessive fertilization has caused low nutrient use
efficiency and high environmental costs in grain production. We analysed the key
requirements underpinning increased sustainability of crop production in China,
as follows: (i) enhance nutrient use efficiency and reduce nutrient losses by
fertilizing roots not soil to maximize root/rhizosphere efficiency with
innovative root zone nutrient management; (ii) improve crop productivity and
resource use efficiency by matching the best agronomic management practices with
crop improvement; and (iii) promote technology transfer of the root zone nutrient
management to achieve the target of high yields and high efficiency with low
environmental risks on a broad scale. Coordinating grain production and
environmental protection by increasing the sustainability of nutrient use will be
a key step in achieving sustainable crop production in Chinese agriculture.
PMID- 27489237
TI - Response to the Editor: On the Growth of Hematopoietic Stem Cells and Childhood
Leukemias.
PMID- 27489236
TI - Identification and characterization of wheat drought-responsive MYB transcription
factors involved in the regulation of cuticle biosynthesis.
AB - A plant cuticle forms a hydrophobic layer covering plant organs, and plays an
important role in plant development and protection from environmental stresses.
We examined epicuticular structure, composition, and a MYB-based regulatory
network in two Australian wheat cultivars, RAC875 and Kukri, with contrasting
cuticle appearance (glaucousness) and drought tolerance. Metabolomics and
microscopic analyses of epicuticular waxes revealed that the content of beta
diketones was the major compositional and structural difference between RAC875
and Kukri. The content of beta-diketones remained the same while those of alkanes
and primary alcohols were increased by drought in both cultivars, suggesting that
the interplay of all components rather than a single one defines the difference
in drought tolerance between cultivars. Six wheat genes encoding MYB
transcription factors (TFs) were cloned; four of them were regulated in flag
leaves of both cultivars by rapid dehydration and/or slowly developing cyclic
drought. The involvement of selected MYB TFs in the regulation of cuticle
biosynthesis was confirmed by a transient expression assay in wheat cell culture,
using the promoters of wheat genes encoding cuticle biosynthesis-related enzymes
and the SHINE1 (SHN1) TF. Two functional MYB-responsive elements, specifically
recognized by TaMYB74 but not by other MYB TFs, were localized in the TdSHN1
promoter. Protein structural determinants underlying the binding specificity of
TaMYB74 for functional DNA cis-elements were defined, using 3D protein molecular
modelling. A scheme, linking drought-induced expression of the investigated TFs
with downstream genes that participate in the synthesis of cuticle components, is
proposed.
PMID- 27489238
TI - Feasibility of screening for atrial fibrillation in primary care: Just a
heartbeat away?
PMID- 27489239
TI - Dyspepsia and the microbiome: time to focus on the small intestine.
PMID- 27489241
TI - Anti-NKG2D monoclonal antibody (NNC0142-0002) in active Crohn's disease: a
randomised controlled trial.
AB - OBJECTIVE: Anti-NKG2D (NNC0142-0002) is an antagonising human immunoglobulin G4
monoclonal antibody that binds to natural killer group 2 member D (NKG2D)
receptors, which are expressed by T cells and innate lymphoid cells, and may be
linked to mucosal damage in Crohn's disease (CD). DESIGN: Seventy-eight patients
(aged >=18 and <=75 years) with CD for >=3 months, Crohn's Disease Activity Index
(CDAI) >=220 and <=450 and either C-reactive protein >=10 mg/L or endoscopic
evidence of inflammation, were randomised 1:1 to a single subcutaneous (SC) dose
of 2 mg/kg anti-NKG2D or placebo. Primary endpoint was change in CDAI (DeltaCDAI)
from baseline to week 4. Prespecified significance level was 10% for CDAI
endpoints. A futility analysis was instituted due to slow recruitment. RESULTS:
Primary endpoint was not significantly different between anti-NKG2D and placebo
(week 4 DeltaCDAI=-16); however, there was a significant difference by week 12
(DeltaCDAI=-55; p<=0.10). Significant improvements were noted in the non-failure
to biologics subgroup (treated with anti-NKG2D (n=28)) from week 1 onward.
Greater effects of anti-NKG2D were also observed in patients with baseline CDAI
>=330. Frequencies of adverse events (AEs) were comparable between anti-NKG2D and
placebo. Most AEs were mild (49%) or moderate (43%). No antidrug antibodies were
observed. CONCLUSIONS: A single SC dose of 2 mg/kg anti-NKG2D did not reduce
disease activity at week 4 versus placebo, but the difference was significant at
week 12, and effects were evident in key subgroups. These data support further
development of anti-NKG2D in IBD. TRIAL REGISTRATION NUMBER: NCT01203631.
PMID- 27489242
TI - Locked Away: Percutaneous Closure of a Malignant Left Atrial Appendage to
Constrain an Unresolvable Thrombus.
PMID- 27489244
TI - The Impact of Diabetes and Comorbidities on the Outcome of Heart Failure Patients
Treated With Cardiac Resynchronization Therapy: Implications for Patient
Management.
PMID- 27489243
TI - Diabetes Mellitus and Outcomes of Cardiac Resynchronization With Implantable
Cardioverter-Defibrillator Therapy in Older Patients With Heart Failure.
AB - BACKGROUND: Large-scale data on outcomes with cardiac resynchronization therapy
with defibrillator in patients with diabetes mellitus are limited. We compared
outcomes after cardiac resynchronization therapy with defibrillator implantation
among patients with heart failure who have diabetes mellitus versus those without
diabetes mellitus. METHODS AND RESULTS: Survival curves and covariate adjusted
hazard ratio (HR) or odds ratio were used to assess the risks for death,
readmission, and device-related complications by diabetes mellitus status among
18 428 patients at least 65 years old receiving cardiac resynchronization therapy
with defibrillator from the National Cardiovascular Data Registry, implantable
cardioverter-defibrillator registry between 2006 and 2009, with up to 3 years of
follow-up. Accounting for differences between groups, compared with those without
diabetes mellitus (n=11 345), patients with diabetes mellitus (n=7083) had a
higher risk of death both at 1 year (HR, 1.16 [95% confidence interval (CI), 1.05
1.29]; P=0.0037) and 3 years (HR, 1.21 [1.14-1.29]; P<0.001) after device
implantation and higher risks of all-cause readmission (sub-HR, 1.16 [1.11-1.21]
at 1 year; P<0.0001; sub-HR, 1.15 [1.11-1.19] at 3 years; P<0.0001) and heart
failure-related readmission (sub-HR, 1.18 [1.09-1.28] at 1 year; P<0.0001; and
sub-HR, 1.22 [1.15-1.30] at 3 years; P<0.0001). Device-related complications
within 90 days did not differ between those with and without diabetes mellitus
(odds ratio: 0.90 [0.77-1.06]; P=0.37). Interactions of age, sex, ischemic
cardiomyopathy, renal failure, or QRS duration were not significant. CONCLUSIONS:
In older patients with heart failure receiving cardiac resynchronization therapy
with defibrillator, diabetes mellitus was independently associated with greater
risks of death and rehospitalization, but similar risks of procedural
complications.
PMID- 27489245
TI - Increased Benefit With Vorapaxar Use in Patients With a History of Myocardial
Infarction and Diabetes Mellitus: What the Data Show Us.
AB - Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial metabolic
disease mainly characterized by hyperglycemia and insulin resistance. Abnormal
platelet reactivity associated with an increased risk of cardiovascular disease
(CVD) is also a feature characteristic of patients with T2DM. Dual antiplatelet
therapy consisting of aspirin and an adenosine diphosphate platelet P2Y12
receptor antagonist, such as clopidogrel, represents the standard antithrombotic
regimen for the secondary prevention of CVD risk in T2DM. However, a high
proportion of patients with T2DM exhibit high on-treatment platelet reactivity to
aspirin and/or clopidogrel, associated with a greater risk of adverse
cardiovascular events compared with nondiabetic patients. Consequently, novel
antiplatelet therapeutic approaches may be required in order to avoid such
events. Vorapaxar is a novel antiplatelet agent that targets the platelet
protease-activated receptor 1 and inhibits thrombin-induced platelet activation.
Vorapaxar has been studied in 2 phase III clinical trials and has been approved
for use in the secondary prevention of atherothrombotic events in patients with a
previous myocardial infarction (MI) or peripheral arterial disease. New data from
the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic
Ischemic Events (TRA 2 degrees P)-TIMI 50 trial MI cohort demonstrate that the
subgroup of patients with T2DM exhibits increased benefit from vorapaxar use
compared with non-T2DM patients. The aim of the present work is to critically
review the current knowledge concerning vorapaxar use in patients with T2DM as
well as to discuss the possible mechanism(s) underlying vorapaxar's beneficial
effect in T2DM.
PMID- 27489247
TI - Evaluating an Adaptive and Interactive mHealth Smoking Cessation and Medication
Adherence Program: A Randomized Pilot Feasibility Study.
AB - BACKGROUND: Mobile health (mHealth) interventions hold great promise for helping
smokers quit since these programs can have wide reach and facilitate access to
comprehensive, interactive, and adaptive treatment content. However, the
feasibility, acceptability, and effectiveness of these programs remain largely
untested. OBJECTIVE: To assess feasibility and acceptability of the My Mobile
Advice Program (MyMAP) smoking cessation program and estimate its effects on
smoking cessation and medication adherence to inform future research planning.
METHODS: Sixty-six smokers ready to quit were recruited from a large regional
health care system and randomized to one of two mHealth programs: (1) standard
self-help including psychoeducational materials and guidance how to quit smoking
or (2) an adaptive and interactive program consisting of the same standard
mHealth self-help content as controls received plus a) real-time, adaptively
tailored advice for managing nicotine withdrawal symptoms and medication side
effects and b) asynchronous secure messaging with a cessation counselor.
Participants in both arms were also prescribed a 12-week course of varenicline.
Follow-up assessments were conducted at 2 weeks post-target quit date (TQD), 3
months post-TQD, and 5 months post-TQD. Indices of program feasibility and
acceptability included acceptability ratings, utilization metrics including use
of each MyMAP program component (self-help content, secure messaging, and
adaptively tailored advice), and open-ended feedback from participants. Smoking
abstinence and medication adherence were also assessed to estimate effects on
these treatment outcomes. RESULTS: Utilization data indicated the MyMAP program
was actively used, with higher mean program log-ins by experimental than control
participants (10.6 vs 2.7, P<.001). The majority of experimental respondents
thought the MyMAP program could help other people quit smoking (22/24, 92%) and
consistently take their stop-smoking medication (17/22, 97%) and would recommend
the program to others (20/23, 87%). They also rated the program as convenient,
responsive to their needs, and easy to use. Abstinence rates at 5-month follow-up
were 36% in the experimental arm versus 24% among controls (odds ratio 1.79 [0.61
5.19], P=.42). Experimental participants used their varenicline an average of 46
days versus 39 among controls (P=.49). More than two-thirds (22/33, 67%) of
experimental participants and three-quarters (25/33, 76%) of controls prematurely
discontinued their varenicline use (P=.29). CONCLUSIONS: The MyMAP intervention
was found to be feasible and acceptable. Since the study was not powered for
statistical significance, no conclusions can be drawn about the program's effects
on smoking abstinence or medication adherence, but the overall study results
suggest further evaluation in a larger randomized trial is warranted.
CLINICALTRIAL: ClinicalTrials.gov NCT02136498;
https://clinicaltrials.gov/ct2/show/NCT02136498 (Archived by WebCite at
http://www.webcitation.org/6jT3UMFLj).
PMID- 27489246
TI - Functional conservation of MBD proteins: MeCP2 and Drosophila MBD proteins alter
sleep.
AB - Proteins containing a methyl-CpG-binding domain (MBD) bind 5mC and convert the
methylation pattern information into appropriate functional cellular states. The
correct readout of epigenetic marks is of particular importance in the nervous
system where abnormal expression or compromised MBD protein function, can lead to
disease and developmental disorders. Recent evidence indicates that the genome of
Drosophila melanogaster is methylated and two MBD proteins, dMBD2/3 and dMBD-R2,
are present. Are Drosophila MBD proteins required for neuronal function, and as
MBD-containing proteins have diverged and evolved, does the MBD domain retain the
molecular properties required for conserved cellular function across species? To
address these questions, we expressed the human MBD-containing protein, hMeCP2,
in distinct amine neurons and quantified functional changes in sleep circuitry
output using a high throughput assay in Drosophila. hMeCP2 expression resulted in
phase-specific sleep loss and sleep fragmentation with the hMeCP2-mediated sleep
deficits requiring an intact MBD domain. Reducing endogenous dMBD2/3 and dMBD-R2
levels also generated sleep fragmentation, with an increase in sleep occurring
upon dMBD-R2 reduction. To examine if hMeCP2 and dMBD-R2 are targeting common
neuronal functions, we reduced dMBD-R2 levels in combination with hMeCP2
expression and observed a complete rescue of sleep deficits. Furthermore,
chromosomal binding experiments indicate MBD-R2 and MeCP2 associate on shared
genomic loci. Our results provide the first demonstration that Drosophila MBD
containing family members are required for neuronal function and suggest that the
MBD domain retains considerable functional conservation at the whole organism
level across species.
PMID- 27489240
TI - Ulcerative proctitis is a frequent location of paediatric-onset UC and not a
minor disease: a population-based study.
AB - OBJECTIVE: Natural history of paediatric-onset ulcerative proctitis (UP) is
poorly described. Our aim was to describe the phenotype and disease course of
incident UP in a population-based study of paediatric-onset UC. PATIENTS AND
METHODS: All patients with UC diagnosed <17 years from 1988 to 2004, and followed
during >2 years have been extracted from a population-based registry. UC location
was defined according to the Paris classification. Cumulative risks for use of
immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-alpha) therapy,
colonic extension and colectomy were described using Kaplan-Meier method. Risk
factors for colonic extension were assessed using Cox proportional hazards
models. RESULTS: 158 patients with paediatric-onset UC (91 females) with a median
age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and
followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at
diagnosis and 49% of them presented a colonic extension at maximal follow-up. In
these children, the cumulative risk for colonic extension was 10% at 1 year, 45%
at 5 years and 52% at 10 years. No parameter at diagnosis was associated with
colonic extension in the UP (E1 group). IS use was significantly lower in
patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP
cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13%
at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti
TNF-alpha and colectomy did not differ between the E1 group and the E2-E3-E4
group. CONCLUSIONS: UP is frequent in paediatric-onset UC and should not be
considered as a minor disease. Compared with more extensive UC locations, risks
for colonic extension, anti-TNF-alpha therapy and colectomy were similar in UP,
whereas the risk for use of IM was lower.
PMID- 27489248
TI - Roles of long noncoding RNAs in chromosome domains.
AB - The cell nucleus is highly organized and functionally compartmentalized. Double
stranded naked DNA is complexed with core histones and assembled into nucleosomes
and chromatin, which are surrounded by nuclear domains composed of RNAs and
proteins. Recently, three-dimensional views of chromosome organization beyond the
level of the nucleosome have been established and are composed of several layers
of chromosome domains. Only a small portion of the human genome encodes proteins;
the majority is pervasively transcribed into noncoding RNAs whose functions are
under intensive investigation. Importantly, the questions of how nuclear retained
noncoding RNAs play roles in orchestrating the chromatin structure that have been
addressed. We discuss the novel noncoding RNA clusters, Eleanors, which are
derived from a large chromatin domain. They accumulate at the site of their own
transcription to form RNA clouds in the nucleus, and they activate gene
expression in the chromatin domain. Noncoding RNAs have emerging roles in genome
regulation that are integrated into the spatial organization of chromatin and the
nucleus. WIREs RNA 2017, 8:e1384. doi: 10.1002/wrna.1384 For further resources
related to this article, please visit the WIREs website.
PMID- 27489249
TI - First Reported Case of MitraClip Placement Due to Mitral Valve Flail in the
Setting of Cardiac Amyloidosis.
PMID- 27489251
TI - Diabetes-related stigma affects the quality of life of people living with
diabetes mellitus in Switzerland: implications for healthcare providers.
AB - There is a growing body of scientific evidence that stigma represents a reality
for many people living with diabetes (PWD). However, little is known about the
impact of experienced stigma. Against this background, the present study aimed to
establish, by means of an in-depth consideration of the situation in Switzerland,
whether and how experienced and perceived stigma impact the quality of life of
those PWD affected. In this cross-sectional study, an anonymous paper-and-pencil
self-administered questionnaire (SAQ) was used for data collection. The SAQ drew
on a qualitative elicitation study and was distributed in 2013 to the readers of
a Swiss journal destined to people living with diabetes. Data were analysed using
descriptive statistics and structural equation modelling. The sample included
3347 people (response rate of 16%) with type 1 and 2 diabetes, aged 16-96.
Respondents who reported higher levels of perceived stigma reported higher levels
of psychological distress (beta = 0.37), more pronounced depressive symptoms
(beta = 0.33) and less social support (beta = -0.22). Higher psychological
distress (beta = -0.29) and more pronounced depressive symptoms (beta = -0.28),
in turn, predicted lower quality of life. Findings suggest that stigma should be
considered as an additional predictor of quality of life in PWD. Therefore,
healthcare providers should support PWD's fight against stigma. Especially,
social workers are called to engage in advocacy to reduce discrimination against
PWD and claim equal chances for them. They are also called to develop and
implement interventions to correct stereotypes about PWD.
PMID- 27489250
TI - An assessment of a massively parallel sequencing approach for the identification
of individuals from mass graves of the Spanish Civil War (1936-1939).
AB - Next-generation sequencing technologies have opened new opportunities in forensic
genetics. Here, we assess the applicability and performance of the MiSeq FGxTM &
ForenSeqTM DNA Signature Prep Kit (Illumina) for the identification of
individuals from the mass graves of the Spanish Civil War (1936-1939). The main
limitations for individual identification are the low number of possible first
degree living relatives and the high levels of DNA degradation reported in
previous studies. Massively parallel sequencing technologies enabling the
analysis of hundreds of regions and prioritizing short length amplicons
constitute a promising tool for this kind of approaches. In this study, we first
explore the power of this new technology to detect first- and second-degree
kinship given different scenarios of DNA degradation. Second, we specifically
assess its performance in a set of low DNA input samples previously analyzed with
CE technologies. We conclude that this methodology will allow identification of
up to second-degree relatives, even in situations with low sequencing performance
and important levels of allele drop-out; it is thus a technology that resolves
previous drawbacks and that will allow a successful approximation to the
identification of remains.
PMID- 27489253
TI - Novel Concordance Between Geographic, Environmental, and Genetic Structure in the
Ecological Generalist Prickly Sculpin (Cottus asper) in California.
AB - Ecological generalists may contain a wealth of information concerning diversity,
ecology, and geographic connectivity throughout their range. We explored these
ideas in prickly sculpin (Cottus asper), a small generalist freshwater fish
species where coastal forms have potentially undergone radiations into inland
lacustrine and riverine environments. Using a 962bp cytochrome b mtDNA marker and
11 microsatellites, we estimated diversity, divergence times, gene flow, and
structure among populations at 43 locations throughout California. We then
incorporated genetic and GIS data into ecological niche models to assess
ecological conditions within identified groups. Though not reciprocally
monophyletic, unique mtDNA haplotypes, microsatellite clustering, and measures of
isolation by distance (Coastal: r = 0.960, P < 0.001; Inland: r = 0.277, P =
0.148) suggest 2 novel taxonomic groups, Coastal and Inland (constrained to Great
Central Valley). Divergence estimates of 41-191 kya combined with the regional
biogeographic history suggest geographic barriers are absent between groups since
divergence, but ecological niche modeling revealed significant environmental
differences (t = 10.84, P < 0.001). Introgressed individuals were also discovered
between groups in an ecologically and geographically intermediate region.
Population structure was limited, predominately found in tributaries of the San
Joaquin basin in the Inland group. Overall, C. asper exhibited substantial
genetic diversity, despite its ecological generality, reflecting California's
historically unique and complex hydrology. More broadly, this study illustrates
variable environments within the range of a generalist species may mask genetic
divergences and should not be overlooked in biodiversity assessments.
PMID- 27489252
TI - Heritability of Recurrent Exertional Rhabdomyolysis in Standardbred and
Thoroughbred Racehorses Derived From SNP Genotyping Data.
AB - Recurrent exertional rhabdomyolysis (RER) in Thoroughbred and Standardbred
racehorses is characterized by episodes of muscle rigidity and cell damage that
often recur upon strenuous exercise. The objective was to evaluate the importance
of genetic factors in RER by obtaining an unbiased estimate of heritability in
cohorts of unrelated Thoroughbred and Standardbred racehorses. Four hundred
ninety-one Thoroughbred and 196 Standardbred racehorses were genotyped with the
54K or 74K SNP genotyping arrays. Heritability was calculated from genome-wide
SNP data with a mixed linear and Bayesian model, utilizing the standard genetic
relationship matrix (GRM). Both the mixed linear and Bayesian models estimated
heritability of RER in Thoroughbreds to be approximately 0.34 and in Standardbred
racehorses to be approximately 0.45 after adjusting for disease prevalence and
sex. To account for potential differences in the genetic architecture of the
underlying causal variants, heritability estimates were adjusted based on linkage
disequilibrium weighted kinship matrix, minor allele frequency and variant effect
size, yielding heritability estimates that ranged between 0.41-0.46
(Thoroughbreds) and 0.39-0.49 (Standardbreds). In conclusion, between 34-46% and
39-49% of the variance in RER susceptibility in Thoroughbred and Standardbred
racehorses, respectively, can be explained by the SNPs present on these 2
genotyping arrays, indicating that RER is moderately heritable. These data
provide further rationale for the investigation of genetic mutations associated
with RER susceptibility.
PMID- 27489255
TI - Comparison of second-line immunosuppressants for childhood refractory nephrotic
syndrome: a systematic review and network meta-analysis.
AB - Although, most patients respond initially to therapy for nephrotic syndrome,
about 70% of patients have a relapse. Currently, there is no consensus about the
most appropriate second-line agent in children who continue to suffer a relapse.
This network meta-analysis was designed to compare the efficacy and safety of the
commonly used immunosuppressive agents in second-line therapeutic agents (ie,
cyclophosphamide, cyclosporine, tacrolimus and mycophenolate mofetil) for
refractory childhood nephrotic syndrome. MEDLINE, Cochrane, EMBASE and Google
Scholar databases were searched until October 17, 2015 using the following search
terms: cyclophosphamide, cyclosporine, tacrolimus, mycophenolate mofetil and
childhood nephrotic syndrome. Randomized controlled trials, prospective 2-arm
studies and cohort studies were included. 7 studies with 391 patients were
included. Bayesian network meta-analysis found that treatment with mycophenolate
mofetil had the greatest odds of relapse compared with tacrolimus (pooled
OR=49.72, 95% credibility interval (CrI) 1.65 to 2483.32), cyclophosphamide
(pooled OR=72.05, 95% CrI 1.44 to 13633.33) and cyclosporine (pooled OR=11.42,
95% CrI 1.03 to 131.60). Rank probability analysis found cyclophosphamide was the
best treatment with the lowest relapse rate as compared with other treatments
(rank probability=0.58), and tacrolimus was ranked as the second best (rank
probability=0.38). Our findings support the use of cyclophosphamide and
tacrolimus in treating children with relapsing nephrotic syndrome.
PMID- 27489254
TI - Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.
AB - BACKGROUND: Impairments of mitochondrial function in the heart are linked
intricately to the development of heart failure, but there is no therapy for
mitochondrial dysfunction. METHODS: We assessed the reduced/oxidized ratio of
nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in
the failing heart. Proteome and acetylome analyses were followed by docking
calculation, mutagenesis, and mitochondrial calcium uptake assays to determine
the functional role of specific acetylation sites. The therapeutic effects of
normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also
were tested. RESULTS: Increased NADH/NAD(+) and protein hyperacetylation,
previously observed in genetic models of defective mitochondrial function, also
are present in human failing hearts as well as in mouse hearts with pathologic
hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway
suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and
improved cardiac function in responses to stresses. Acetylome analysis identified
a subpopulation of mitochondrial proteins that was sensitive to changes in the
NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle
proteins impaired the transport and oxidation of cytosolic NADH in the
mitochondria, resulting in altered cytosolic redox state and energy deficiency.
Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70
in adenosine triphosphate synthase complex promoted its interaction with
cyclophilin D, and sensitized the opening of mitochondrial permeability
transition pore. Both could be alleviated by normalizing the NAD(+) redox balance
either genetically or pharmacologically. CONCLUSIONS: We show that mitochondrial
protein hyperacetylation due to NAD(+) redox imbalance contributes to the
pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical
data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the
failing hearts. These findings have a high translational potential as the
pharmacologic strategy of increasing NAD(+) precursors are feasible in humans.
PMID- 27489256
TI - P values: from suggestion to superstition.
AB - A threshold probability value of 'p<=0.05' is commonly used in clinical
investigations to indicate statistical significance. To allow clinicians to
better understand evidence generated by research studies, this review defines the
p value, summarizes the historical origins of the p value approach to hypothesis
testing, describes various applications of p<=0.05 in the context of clinical
research and discusses the emergence of p<=5*10(-8) and other values as
thresholds for genomic statistical analyses. Corresponding issues include a
conceptual approach of evaluating whether data do not conform to a null
hypothesis (ie, no exposure-outcome association). Importantly, and in the
historical context of when p<=0.05 was first proposed, the 1-in-20 chance of a
false-positive inference (ie, falsely concluding the existence of an exposure
outcome association) was offered only as a suggestion. In current usage, however,
p<=0.05 is often misunderstood as a rigid threshold, sometimes with a misguided
'win' (p<=0.05) or 'lose' (p>0.05) approach. Also, in contemporary genomic
studies, a threshold of p<=10(-8) has been endorsed as a boundary for statistical
significance when analyzing numerous genetic comparisons for each participant. A
value of p<=0.05, or other thresholds, should not be employed reflexively to
determine whether a clinical research investigation is trustworthy from a
scientific perspective. Rather, and in parallel with conceptual issues of
validity and generalizability, quantitative results should be interpreted using a
combined assessment of strength of association, p values, CIs, and sample size.
PMID- 27489258
TI - Older workers-workplace health evidence-based practice?
PMID- 27489259
TI - Jean-Charles Develly, Impression sur etoffes. Teinture (Printing fabrics. Dyeing)
c.1830.
PMID- 27489260
TI - More hot air.
PMID- 27489262
TI - Comment on: 'Systematic review of the cardiovascular effects of occupational
noise' by Skogstad et al.
PMID- 27489263
TI - Response to letter from Dr Dzhambow.
PMID- 27489264
TI - Systematic review of the cardiovascular effects of occupational noise.
PMID- 27489265
TI - Changes in Structure and Antigenicity of HIV-1 Env Trimers Resulting from Removal
of a Conserved CD4 Binding Site-Proximal Glycan.
AB - The envelope glycoprotein (Env) is the major target for HIV-1 broadly
neutralizing antibodies (bNAbs). One of the mechanisms that HIV has evolved to
escape the host's immune response is to mask conserved epitopes on Env with dense
glycosylation. Previous studies have shown that the removal of a particular
conserved glycan at N197 increases the neutralization sensitivity of the virus to
antibodies targeting the CD4 binding site (CD4bs), making it a site of
significant interest from the perspective of vaccine design. At present, the
structural consequences that result from the removal of the N197 glycan have not
been characterized. Using native-like SOSIP trimers, we examine the effects on
antigenicity and local structural dynamics resulting from the removal of this
glycan. A large increase in the binding of CD4bs and V3-targeting antibodies is
observed for the N197Q mutant in trimeric Env, while no changes are observed with
monomeric gp120. While the overall structure and thermostability are not altered,
a subtle increase in the flexibility of the variable loops at the trimeric
interface of adjacent protomers is evident in the N197Q mutant by hydrogen
deuterium exchange mass spectrometry. Structural modeling of the glycan chains
suggests that the spatial occupancy of the N197 glycan leads to steric clashes
with CD4bs antibodies in the Env trimer but not monomeric gp120. Our results
indicate that the removal of the N197 glycan enhances the exposure of relevant
bNAb epitopes on Env with a minimal impact on the overall trimeric structure.
These findings present a simple modification for enhancing trimeric Env
immunogens in vaccines. IMPORTANCE: The HIV-1 Env glycoprotein presents a dense
patchwork of host cell-derived N-linked glycans. This so-called glycan shield is
considered to be a major protective mechanism against immune recognition. While
the positions of many N-linked glycans are isolate specific, some are highly
conserved and are believed to play key functional roles. In this study, we
examine the conserved, CD4 binding site-proximal N197 glycan and demonstrate that
its removal both facilitates neutralizing antibody access to the CD4 binding site
and modestly impacts the structural dynamics at the trimer crown without
drastically altering global Env trimer stability. This indicates that surgical
glycosylation site modification may be an effective way of sculpting epitope
presentation in Env-based vaccines.
PMID- 27489266
TI - Mutations That Determine Resistance Breaking in a Plant RNA Virus Have
Pleiotropic Effects on Its Fitness That Depend on the Host Environment and on the
Type, Single or Mixed, of Infection.
AB - Overcoming host resistance in gene-for-gene host-virus interactions is an
important instance of host range expansion, which can be hindered by across-host
fitness trade-offs. Trade-offs are generated by negative effects of host range
mutations on the virus fitness in the original host, i.e., by antagonistic
pleiotropy. It has been reported that different mutations in Pepper mild mottle
virus (PMMoV) coat protein result in overcoming L-gene resistance in pepper. To
analyze if resistance-breaking mutations in PMMoV result in antagonistic
pleiotropy, all reported mutations determining the overcoming of L(3) and L(4)
alleles were introduced in biologically active cDNA clones. Then, the parental
and mutant virus genotypes were assayed in susceptible pepper genotypes with an
L(+), L(1), or L(2) allele, in single and in mixed infections. Resistance
breaking mutations had pleiotropic effects on the virus fitness that, according
to the specific mutation, the host genotype, and the type of infection, single or
mixed with other virus genotypes, were antagonistic or positive. Thus, resistance
breaking mutations can generate fitness trade-offs both across hosts and across
types of infection, and the frequency of host range mutants will depend on the
genetic structure of the host population and on the frequency of mixed infections
by different virus genotypes. Also, resistance-breaking mutations variously
affected virulence, which may further influence the evolution of host range
expansion. IMPORTANCE: A major cause of virus emergence is host range expansion,
which may be hindered by across-host fitness trade-offs caused by negative
pleiotropy of host range mutations. An important instance of host range expansion
is overcoming host resistance in gene-for-gene plant-virus interactions. We
analyze here if mutations in the coat protein of Pepper mild mottle virus
determining L-gene resistance-breaking in pepper have associated fitness
penalties in susceptible host genotypes. Results show that pleiotropic effects of
resistance-breaking mutations on virus fitness depend on the specific mutation,
the susceptible host genotype, and the type of infection, single or mixed, with
other virus genotypes. Accordingly, resistance-breaking mutations can have
negative, positive, or no pleiotropic effects on virus fitness. These results
underscore the complexity of host range expansion evolution and, specifically,
the difficulty of predicting the overcoming of resistance factors in crops.
PMID- 27489267
TI - Acute Liver Damage Associated with Innate Immune Activation in a Small Nonhuman
Primate Model of Hepacivirus Infection.
AB - Despite its importance in shaping adaptive immune responses, viral clearance, and
immune-based inflammation, tissue-specific innate immunity remains poorly
characterized for hepatitis C virus (HCV) infection due to the lack of access to
acutely infected tissues. In this study, we evaluated the impact of natural
killer (NK) cells and myeloid (mDCs) and plasmacytoid (pDCs) dendritic cells on
control of virus replication and virus-induced pathology caused by another, more
rapidly resolving hepacivirus, GB virus B (GBV-B), in infections of common
marmosets. High plasma and liver viral loads and robust hepatitis characterized
acute GBV-B infection, and while viremia was generally cleared by 2 to 3 months
postinfection, hepatitis and liver fibrosis persisted after clearance. Coinciding
with peak viral loads and liver pathology, the levels of NK cells, mDCs, and pDCs
in the liver increased up to 3-fold. Although no obvious numerical changes in
peripheral innate cells occurred, circulating NK cells exhibited increased
perforin and Ki67 expression levels and increased surface expression of CXCR3.
These data suggested that increased NK cell arming and proliferation as well as
tissue trafficking may be associated with influx into the liver during acute
infection. Indeed, NK cell frequencies in the liver positively correlated with
plasma (R = 0.698; P = 0.015) and liver (R = 0.567; P = 0.057) viral loads.
Finally, soluble factors associated with NK cells and DCs, including gamma
interferon (IFN-gamma) and RANTES, were increased in acute infection and also
were associated with viral loads and hepatitis. Collectively, the findings showed
that mobilization of local and circulating innate immune responses was linked to
acute virus-induced hepatitis, and potentially to resolution of GBV-B infection,
and our results may provide insight into similar mechanisms in HCV infection.
IMPORTANCE: Hepatitis C virus (HCV) infection has created a global health crisis,
and despite new effective antivirals, it is still a leading cause of liver
disease and death worldwide. Recent evidence suggests that innate immunity may be
a potential therapeutic target for HCV, but it may also be a correlate of
increased disease. Due to a lack of access to human tissues with acute HCV
infection, in this study we evaluated the role of innate immunity in resolving
infection with a hepacivirus, GBV-B, in common marmosets. Collectively, our data
suggest that NK cell and DC mobilization in acute hepacivirus infection can
dampen virus replication but also regulate acute and chronic liver damage. How
these two opposing effects on the host may be modulated in future therapeutic and
vaccine approaches warrants further study.
PMID- 27489268
TI - Infectious Progression of Canine Distemper Virus from Circulating Cerebrospinal
Fluid into the Central Nervous System.
AB - In the current study, we generated recombinant chimeric canine distemper viruses
(CDVs) by replacing the hemagglutinin (H) and/or phosphoprotein (P) gene in an
avirulent strain expressing enhanced green fluorescent protein (EGFP) with those
of a mouse-adapted neurovirulent strain. An in vitro experimental infection
indicated that the chimeric CDVs possessing the H gene derived from the mouse
adapted CDV acquired infectivity for neural cells. These cells lack the CDV
receptors that have been identified to date (SLAM and nectin-4), indicating that
the H protein defines infectivity in various cell lines. The recombinant viruses
were administered intracerebrally to 1-week-old mice. Fatal neurological signs of
disease were observed only with a recombinant CDV that possessed both the H and P
genes of the mouse-adapted strain, similar to the parental mouse-adapted strain,
suggesting that both genes are important to drive virulence of CDV in mice. Using
this recombinant CDV, we traced the intracerebral propagation of CDV by detecting
EGFP. Widespread infection was observed in the cerebral hemispheres and
brainstems of the infected mice. In addition, EGFP fluorescence in the brain
slices demonstrated a sequential infectious progression in the central nervous
system: CDV primarily infected the neuroependymal cells lining the ventricular
wall and the neurons of the hippocampus and cortex adjacent to the ventricle, and
it then progressed to an extensive infection of the brain surface, followed by
the parenchyma and cortex. In the hippocampal formation, CDV spread in a
unidirectional retrograde pattern along neuronal processes in the hippocampal
formation from the CA1 region to the CA3 region and the dentate gyrus. Our mouse
model demonstrated that the main target cells of CDV are neurons in the acute
phase and that the virus spreads via neuronal transmission pathways in the
hippocampal formation. IMPORTANCE: CDV is the etiological agent of distemper in
dogs and other carnivores, and in many respects, the pathogenesis of CDV
infection in animals resembles that of measles virus infection in humans. We
successfully generated a recombinant CDV containing the H and P genes from a
mouse-adapted neurovirulent strain and expressing EGFP. The recombinant CDV
exhibited severe neurovirulence with high mortality, comparable to the parental
mouse-adapted strain. The mouse-infectious model could become a useful tool for
analyzing CDV infection of the central nervous system subsequent to passing
through the blood-cerebrospinal fluid barrier and infectious progression in the
target cells in acute disease.
PMID- 27489269
TI - Ferrets Infected with Bundibugyo Virus or Ebola Virus Recapitulate Important
Aspects of Human Filovirus Disease.
AB - Bundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in
humans with a case-fatality rate ranging from 25 to 36%. Despite having been
known to the scientific and medical communities for almost 1 decade, there is a
dearth of studies on this pathogen due to the lack of a small animal model.
Domestic ferrets are commonly used to study other RNA viruses, including members
of the order Mononegavirales To investigate whether ferrets were susceptible to
filovirus infections, ferrets were challenged with a clinical isolate of BDBV.
Animals became viremic within 4 days and succumbed to infection between 8 and 9
days, and a petechial rash was observed with moribund ferrets. Furthermore,
several hallmarks of human filoviral disease were recapitulated in the ferret
model, including substantial decreases in lymphocyte and platelet counts and
dysregulation of key biochemical markers related to hepatic/renal function, as
well as coagulation abnormalities. Virological, histopathological, and
immunohistochemical analyses confirmed uncontrolled BDBV replication in the major
organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their
susceptibility to another filovirus species and to potentially establish a virus
transmission model. Similar to what was seen with BDBV, important hallmarks of
human filoviral disease were observed in EBOV-infected ferrets. This study
demonstrates the potential of this small animal model for studying BDBV and EBOV
using wild-type isolates and will accelerate efforts to understand filovirus
pathogenesis and transmission as well as the development of specific vaccines and
antivirals. IMPORTANCE: The 2013-2016 outbreak of Ebola virus in West Africa has
highlighted the threat posed by filoviruses to global public health. Bundibugyo
virus (BDBV) is a member of the genus Ebolavirus and has caused outbreaks in the
past but is relatively understudied, likely due to the lack of a suitable small
animal model. Such a model for BDBV is crucial to evaluating vaccines and
therapies and potentially understanding transmission. To address this, we
demonstrated that ferrets are susceptible models to BDBV infection as well as to
Ebola virus infection and that no virus adaptation is required. Moreover, these
animals develop a disease that is similar to that seen in humans and nonhuman
primates. We believe that this will improve the ability to study BDBV and provide
a platform to test vaccines and therapeutics.
PMID- 27489270
TI - Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection
in Human Lung Cells and Airway Tissues.
AB - Human metapneumovirus (HMPV), a recently discovered paramyxovirus, infects nearly
100% of the world population and causes severe respiratory disease in infants,
the elderly, and immunocompromised patients. We previously showed that HMPV binds
heparan sulfate proteoglycans (HSPGs) and that HMPV binding requires only the
viral fusion (F) protein. To characterize the features of this interaction
critical for HMPV binding and the role of this interaction in infection in
relevant models, we utilized sulfated polysaccharides, heparan sulfate mimetics,
and occluding compounds. Iota-carrageenan demonstrated potent anti-HMPV activity
by inhibiting binding to lung cells mediated by the F protein. Furthermore,
analysis of a minilibrary of variably sulfated derivatives of Escherichia coli K5
polysaccharide mimicking the HS structure revealed that the highly O-sulfated K5
polysaccharides inhibited HMPV infection, identifying a potential feature of HS
critical for HMPV binding. The peptide dendrimer SB105-A10, which binds HS,
reduced binding and infection in an F-dependent manner, suggesting that occlusion
of HS at the target cell surface is sufficient to prevent infection. HMPV
infection was also inhibited by these compounds during apical infection of
polarized airway tissues, suggesting that these interactions take place during
HMPV infection in a physiologically relevant model. These results reveal key
features of the interaction between HMPV and HS, supporting the hypothesis that
apical HS in the airway serves as a binding factor during infection, and HS
modulating compounds may serve as a platform for potential antiviral development.
IMPORTANCE: Human metapneumovirus (HMPV) is a paramyxovirus that causes
respiratory disease worldwide. It has been previously shown that HMPV requires
binding to heparan sulfate on the surfaces of target cells for attachment and
infection. In this study, we characterize the key features of this binding
interaction using heparan sulfate mimetics, identify an important sulfate
modification, and demonstrate that these interactions occur at the apical surface
of polarized airway tissues. These findings provide insights into the initial
binding step of HMPV infection that has potential for antiviral development.
PMID- 27489271
TI - Serine/Arginine-Rich Splicing Factor 3 and Heterogeneous Nuclear
Ribonucleoprotein A1 Regulate Alternative RNA Splicing and Gene Expression of
Human Papillomavirus 18 through Two Functionally Distinguishable cis Elements.
AB - Human papillomavirus 18 (HPV18) is the second most common oncogenic HPV type
associated with cervical, anogenital, and oropharyngeal cancers. Like other
oncogenic HPVs, HPV18 encodes two major (one early and one late) polycistronic
pre-mRNAs that are regulated by alternative RNA splicing to produce a repertoire
of viral transcripts for the expression of individual viral genes. However, RNA
cis-regulatory elements and trans-acting factors contributing to HPV18
alternative RNA splicing remain unknown. In this study, an exonic splicing
enhancer (ESE) in the nucleotide (nt) 3520 to 3550 region in the HPV18 genome was
identified and characterized for promotion of HPV18 929^3434 splicing and E1^E4
production through interaction with SRSF3, a host oncogenic splicing factor
differentially expressed in epithelial cells and keratinocytes. Introduction of
point mutations in the SRSF3-binding site or knockdown of SRSF3 expression in
cells reduces 929^3434 splicing and E1^E4 production but activates other, minor
929^3465 and 929^3506 splicing. Knockdown of SRSF3 expression also enhances the
expression of E2 and L1 mRNAs. An exonic splicing silencer (ESS) in the HPV18 nt
612 to 639 region was identified as being inhibitory to the 233^416 splicing of
HPV18 E6E7 pre-mRNAs via binding to hnRNP A1, a well-characterized, abundantly
and ubiquitously expressed RNA-binding protein. Introduction of point mutations
into the hnRNP A1-binding site or knockdown of hnRNP A1 expression promoted
233^416 splicing and reduced E6 expression. These data provide the first evidence
that the alternative RNA splicing of HPV18 pre-mRNAs is subject to regulation by
viral RNA cis elements and host trans-acting splicing factors. IMPORTANCE:
Expression of HPV18 genes is regulated by alternative RNA splicing of viral
polycistronic pre-mRNAs to produce a repertoire of viral early and late
transcripts. RNA cis elements and trans-acting factors contributing to HPV18
alternative RNA splicing have been discovered in this study for the first time.
The identified ESS at the E7 open reading frame (ORF) prevents HPV18 233^416
splicing in the E6 ORF through interaction with a host splicing factor, hnRNP A1,
and regulates E6 and E7 expression of the early E6E7 polycistronic pre-mRNA. The
identified ESE at the E1^E4 ORF promotes HPV18 929^3434 splicing of both viral
early and late pre-mRNAs and E1^E4 production through interaction with SRSF3.
This study provides important observations on how alternative RNA splicing of
HPV18 pre-mRNAs is subject to regulation by viral RNA cis elements and host
splicing factors and offers potential therapeutic targets to overcome HPV-related
cancer.
PMID- 27489272
TI - ITCH E3 Ubiquitin Ligase Interacts with Ebola Virus VP40 To Regulate Budding.
AB - Ebola virus (EBOV) and Marburg virus (MARV) belong to the Filoviridae family and
can cause outbreaks of severe hemorrhagic fever, with high mortality rates in
humans. The EBOV VP40 (eVP40) and MARV VP40 (mVP40) matrix proteins play a
central role in virion assembly and egress, such that independent expression of
VP40 leads to the production and egress of virus-like particles (VLPs) that
accurately mimic the budding of infectious virus. Late (L) budding domains of
eVP40 recruit host proteins (e.g., Tsg101, Nedd4, and Alix) that are important
for efficient virus egress and spread. For example, the PPxY-type L domain of
eVP40 and mVP40 recruits the host Nedd4 E3 ubiquitin ligase via its WW domains to
facilitate budding. Here we sought to identify additional WW domain host
interactors and demonstrate that the PPxY L domain motif of eVP40 interacts
specifically with the WW domain of the host E3 ubiquitin ligase ITCH. ITCH, like
Nedd4, is a member of the HECT class of E3 ubiquitin ligases, and the resultant
physical and functional interaction with eVP40 facilitates VLP and virus budding.
Identification of this novel eVP40 interactor highlights the functional interplay
between cellular E3 ligases, ubiquitination, and regulation of VP40-mediated
egress. IMPORTANCE: The unprecedented magnitude and scope of the recent 2014-2015
EBOV outbreak in West Africa and its emergence here in the United States and
other countries underscore the critical need for a better understanding of the
biology and pathogenesis of this emerging pathogen. We have identified a novel
and functional EBOV VP40 interactor, ITCH, that regulates VP40-mediated egress.
This virus-host interaction may represent a new target for our previously
identified small-molecule inhibitors of virus egress.
PMID- 27489274
TI - Global Transcriptional Analysis of Virus-Host Interactions between Phage phi29
and Bacillus subtilis.
AB - The study of phage-host relationships is essential to understanding the dynamic
of microbial systems. Here, we analyze genome-wide interactions of Bacillus
subtilis and its lytic phage phi29 during the early stage of infection.
Simultaneous high-resolution analysis of virus and host transcriptomes by deep
RNA sequencing allowed us to identify differentially expressed bacterial genes.
Phage phi29 induces significant transcriptional changes in about 0.9% (38/4,242)
and 1.8% (76/4,242) of the host protein-coding genes after 8 and 16 min of
infection, respectively. Gene ontology enrichment analysis clustered upregulated
genes into several functional categories, such as nucleic acid metabolism
(including DNA replication) and protein metabolism (including translation).
Surprisingly, most of the transcriptional repressed genes were involved in the
utilization of specific carbon sources such as ribose and inositol, and many
contained promoter binding-sites for the catabolite control protein A (CcpA).
Another interesting finding is the presence of previously uncharacterized
antisense transcripts complementary to the well-known phage phi29 messenger RNAs
that adds an additional layer to the viral transcriptome complexity. IMPORTANCE:
The specific virus-host interactions that allow phages to redirect cellular
machineries and energy resources to support the viral progeny production are
poorly understood. This study provides, for the first time, an insight into the
genome-wide transcriptional response of the Gram-positive model Bacillus subtilis
to phage phi29 infection.
PMID- 27489273
TI - Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host
Range and Pathogenicity.
AB - Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses.
The A allele is found in avian and mammalian viruses, but the B allele is viewed
as being almost exclusively found in avian viruses. This might reflect the fact
that one or both of its encoded proteins (NS1 and NEP) are maladapted for
replication in mammalian hosts. To test this, a number of clade A and B avian
virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no
case was the peak virus titer substantially reduced following infection of
various mammalian cell types. Exemplar reassortant viruses also replicated to
similar titers in mice, although mice infected with viruses with the avian virus
derived segment 8s had reduced weight loss compared to that achieved in mice
infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped
similarly with type I interferons. Temporal proteomics analysis of cellular
responses to infection showed that the avian virus-derived NS segments provoked
lower levels of expression of interferon-stimulated genes in cells than wild type
derived NS segments. Thus, neither the A nor the B allele of avian virus-derived
NS segments necessarily attenuates virus replication in a mammalian host,
although the alleles can attenuate disease. Phylogenetic analyses identified 32
independent incursions of an avian virus-derived A allele into mammals, whereas 6
introductions of a B allele were identified. However, A-allele isolates from
birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia
transmission were not significantly different. We conclude that while the
introduction of an avian virus segment 8 into mammals is a relatively rare event,
the dogma of the B allele being especially restricted is misleading, with
implications in the assessment of the pandemic potential of avian influenza
viruses. IMPORTANCE: Influenza A virus (IAV) can adapt to poultry and mammalian
species, inflicting a great socioeconomic burden on farming and health care
sectors. Host adaptation likely involves multiple viral factors. Here, we
investigated the role of IAV segment 8. Segment 8 has evolved into two distinct
clades: the A and B alleles. The B-allele genes have previously been suggested to
be restricted to avian virus species. We introduced a selection of avian virus A-
and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that
these reassortant viruses were fully competent in mammalian host systems. We also
analyzed the currently available public data on the segment 8 gene distribution
and found surprisingly little evidence for specific avian host restriction of the
B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable
of supporting infection in mammals and that they should be considered during the
assessment of the pandemic risk of zoonotic influenza A viruses.
PMID- 27489275
TI - Protective Effects of Glutamine Antagonist 6-Diazo-5-Oxo-l-Norleucine in Mice
with Alphavirus Encephalomyelitis.
AB - Inflammation is a necessary part of the response to infection but can also cause
neuronal injury in both infectious and autoimmune diseases of the central nervous
system (CNS). A neurovirulent strain of Sindbis virus (NSV) causes fatal
paralysis in adult C57BL/6 mice during clearance of infectious virus from the
CNS, and the virus-specific immune response is implicated as a mediator of
neuronal damage. Previous studies have shown that survival is improved in T-cell
deficient mice and in mice with pharmacological inhibition of the inflammatory
response and glutamate excitotoxicity. Because glutamine metabolism is important
in the CNS for the generation of glutamate and in the immune system for
lymphocyte proliferation, we tested the effect of the glutamine antagonist DON (6
diazo-5-oxo-l-norleucine) on the outcome of NSV infection in mice. DON treatment
for 7 days from the time of infection delayed the onset of paralysis and death.
Protection was associated with reduced lymphocyte proliferation in the draining
cervical lymph nodes, decreased leukocyte infiltration into the CNS, lower levels
of inflammatory cytokines, and delayed viral clearance. In vitro studies showed
that DON inhibited stimulus-induced proliferation of lymphocytes. When in vivo
treatment with DON was stopped, paralytic disease developed along with the
inflammatory response and viral clearance. These studies show that fatal NSV
induced encephalomyelitis is immune mediated and that antagonists of glutamine
metabolism can modulate the immune response and protect against virus-induced
neuroinflammatory disease. IMPORTANCE: Encephalomyelitis due to infection with
mosquito-borne alphaviruses is an important cause of death and of long-term
neurological disability in those who survive infection. This study demonstrates
the role of the virus-induced immune response in the generation of neurological
disease. DON, a glutamine antagonist, inhibited the proliferation of lymphocytes
in response to infection, prevented the development of brain inflammation, and
protected mice from paralysis and death during treatment. However, because DON
inhibited the immune response to infection, clearance of the virus from the brain
was also prevented. When treatment was stopped, the immune response was
generated, brain inflammation occurred, virus was cleared, and mice developed
paralysis and died. Therefore, more definitive treatment for alphaviral
encephalomyelitis should inhibit virus replication as well as neuroinflammatory
damage.
PMID- 27489276
TI - Flexibility of the Head-Stalk Linker Domain of Paramyxovirus HN Glycoprotein Is
Essential for Triggering Virus Fusion.
AB - The Paramyxoviridae comprise a large family of enveloped, negative-sense, single
stranded RNA viruses with significant economic and public health implications.
For nearly all paramyxoviruses, infection is initiated by fusion of the viral and
host cell plasma membranes in a pH-independent fashion. Fusion is orchestrated by
the receptor binding protein hemagglutinin-neuraminidase (HN; also called H or G
depending on the virus type) protein and a fusion (F) protein, the latter
undergoing a major refolding process to merge the two membranes. Mechanistic
details regarding the coupling of receptor binding to F activation are not fully
understood. Here, we have identified the flexible loop region connecting the
bulky enzymatically active head and the four-helix bundle stalk to be essential
for fusion promotion. Proline substitution in this region of HN of parainfluenza
virus 5 (PIV5) and Newcastle disease virus HN abolishes cell-cell fusion, whereas
HN retains receptor binding and neuraminidase activity. By using reverse
genetics, we engineered recombinant PIV5-EGFP viruses with mutations in the head
stalk linker region of HN. Mutations in this region abolished virus recovery and
infectivity. In sum, our data suggest that the loop region acts as a "hinge"
around which the bulky head of HN swings to-and-fro to facilitate timely HN
mediate F-triggering, a notion consistent with the stalk-mediated activation
model of paramyxovirus fusion. IMPORTANCE: Paramyxovirus fusion with the host
cell plasma membrane is essential for virus infection. Membrane fusion is
orchestrated via interaction of the receptor binding protein (HN, H, or G) with
the viral fusion glycoprotein (F). Two distinct models have been suggested to
describe the mechanism of fusion: these include "the clamp" and the "provocateur"
model of activation. By using biochemical and reverse genetics tools, we have
obtained strong evidence in favor of the HN stalk-mediated activation of
paramyxovirus fusion. Specifically, our data strongly support the notion that the
short linker between the head and stalk plays a role in "conformational
switching" of the head group to facilitate F-HN interaction and triggering.
PMID- 27489277
TI - Mouse Hepatitis Virus Infection Induces a Toll-Like Receptor 2-Dependent
Activation of Inflammatory Functions in Liver Sinusoidal Endothelial Cells during
Acute Hepatitis.
AB - Under physiological conditions, the liver sinusoidal endothelial cells (LSECs)
mediate hepatic immune tolerance toward self or foreign antigens through
constitutive expression of anti-inflammatory mediators. However, upon viral
infection or Toll-like receptor 2 (TLR2) activation, LSECs can achieve
proinflammatory functions, but their role in hepatic inflammation during acute
viral hepatitis is unknown. Using the highly virulent mouse hepatitis virus type
3 (MHV3) and the attenuated variants 51.6-MHV3 and YAC-MHV3, exhibiting lower
tropism for LSECs, we investigated in vivo and in vitro the consequence of LSEC
infection on their proinflammatory profiles and the aggravation of acute
hepatitis process. In vivo infection with virulent MHV3, in comparison to
attenuated strains, resulted in fulminant hepatitis associated with higher
hepatic viral load, tissue necrosis, and levels of inflammatory mediators and
earlier recruitment of inflammatory cells. Such hepatic inflammatory disorders
correlated with disturbed production of interleukin-10 (IL-10) and vascular
factors by LSECs. We next showed in vitro that infection of LSECs by the virulent
MHV3 strain altered their production of anti-inflammatory cytokines and promoted
higher release of proinflammatory and procoagulant factors and earlier cell
damage than infection by attenuated strains. This higher replication and
proinflammatory activation in LSECs by the virulent MHV3 strain was associated
with a specific activation of TLR2 signaling by the virus. We provide evidence
that TLR2 activation of LSCEs by MHV3 is an aggravating factor of hepatic
inflammation and correlates with the severity of hepatitis. Taken together, these
results indicate that preservation of the immunotolerant properties of LSECs
during acute viral hepatitis is imperative in order to limit hepatic inflammation
and damage. IMPORTANCE: Viral hepatitis B and C infections are serious health
problems affecting over 350 million and 170 million people worldwide,
respectively. It has been suggested that a balance between protection and liver
damage mediated by the host's immune response during the acute phase of infection
would be determinant in hepatitis outcome. Thus, it appears crucial to identify
the factors that predispose in exacerbating liver inflammation to limit
hepatocyte injury. Liver sinusoidal endothelial cells (LSECs) can express both
anti- and proinflammatory functions, but their role in acute viral hepatitis has
never been investigated. Using mouse hepatitis virus (MHV) infections as animal
models of viral hepatitis, we report for the first time that in vitro and in vivo
infection of LSECs by the pathogenic MHV3 serotype leads to a reversion of their
intrinsic anti-inflammatory phenotype toward a proinflammatory profile as well to
as disorders in vascular factors, correlating with the severity of hepatitis.
These results highlight a new virus-promoted mechanism of exacerbation of liver
inflammatory response during acute hepatitis.
PMID- 27489278
TI - Entry of Classical Swine Fever Virus into PK-15 Cells via a pH-, Dynamin-, and
Cholesterol-Dependent, Clathrin-Mediated Endocytic Pathway That Requires Rab5 and
Rab7.
AB - Classical swine fever virus (CSFV), a member of the genus Pestivirus within the
family Flaviviridae, is a small, enveloped, positive-strand RNA virus. Due to its
economic importance to the pig industry, the biology and pathogenesis of CSFV
have been investigated extensively. However, the mechanisms of CSFV entry into
cells are not well characterized. In this study, we used systematic approaches to
dissect CSFV cell entry. We first observed that CSFV infection was inhibited by
chloroquine and NH4Cl, suggesting that viral entry required a low-pH environment.
By using the specific inhibitor dynasore, or by expressing the dominant negative
(DN) K44A mutant, we verified that dynamin is required for CSFV entry. CSFV
particles were observed to colocalize with clathrin at 5 min postinternalization,
and CSFV infection was significantly reduced by chlorpromazine treatment,
overexpression of a dominant negative form of the EPS15 protein, or knockdown of
the clathrin heavy chain by RNA interference. These results suggested that CSFV
entry depends on clathrin. Additionally, we found that endocytosis of CSFV was
dependent on membrane cholesterol, while neither the overexpression of a dominant
negative caveolin mutant nor the knockdown of caveolin had an effect. These
results further suggested that CSFV entry required cholesterol and not caveolae.
Importantly, the effect of DN mutants of three Rab proteins that regulate
endosomal traffic on CSFV infection was examined. Expression of DN Rab5 and Rab7
mutants, but not the DN Rab11 mutant, significantly inhibited CSFV replication.
These results were confirmed by silencing of Rab5 and Rab7. Confocal microscopy
showed that virus particles colocalized with Rab5 or Rab7 during the early phase
of infection within 45 min after virus entry. These results indicated that after
internalization, CSFV moved to early and late endosomes before releasing its RNA.
Taken together, our findings demonstrate for the first time that CSFV enters
cells through the endocytic pathway, providing new insights into the life cycle
of pestiviruses. IMPORTANCE: Bovine viral diarrhea virus (BVDV), a single
stranded, positive-sense pestivirus within the family Flaviviridae, is
internalized by clathrin-dependent receptor-mediated endocytosis. However, the
detailed mechanism of cell entry is unknown for other pestiviruses, such as
classical swine fever (CSF) virus (CSFV). CSFV is the etiological agent of CSF, a
highly contagious disease of swine that causes numerous deaths in pigs and
enormous economic losses in China. Understanding the entry pathway of CSFV will
not only advance our knowledge of CSFV infection and pathogenesis but also
provide novel drug targets for antiviral intervention. Based on this objective,
we used systematic approaches to dissect the pathway of entry of CSFV into PK-15
cells. This is the first report to show that the entry of CSFV into PK-15 cells
requires a low-pH environment and involves dynamin- and cholesterol-dependent,
clathrin-mediated endocytosis that requires Rab5 and Rab7.
PMID- 27489279
TI - Neuroinvasion of alpha-Synuclein Prionoids after Intraperitoneal and Intraglossal
Inoculation.
AB - alpha-Synuclein is a soluble, cellular protein that in a number of
neurodegenerative diseases, including Parkinson's disease and multiple system
atrophy, forms pathological deposits of protein aggregates. Because misfolded
alpha-synuclein has some characteristics that resemble those of prions, we
investigated its potential to induce disease after intraperitoneal or
intraglossal challenge injection into bigenic Tg(M83(+/-):Gfap-luc(+/-)) mice,
which express the A53T mutant of human alpha-synuclein and firefly luciferase.
After a single intraperitoneal injection with alpha-synuclein fibrils, four of
five mice developed paralysis and alpha-synuclein pathology in the central
nervous system, with a median incubation time of 229 +/- 17 days. Diseased mice
accumulated aggregates of Sarkosyl-insoluble and phosphorylated alpha-synuclein
in the brain and spinal cord, which colocalized with ubiquitin and p62 and were
accompanied by gliosis. In contrast, only one of five mice developed alpha
synuclein pathology in the central nervous system after intraglossal injection
with alpha-synuclein fibrils, after 285 days. These findings are novel and
important because they show that, similar to prions, alpha-synuclein prionoids
can neuroinvade the central nervous system after intraperitoneal or intraglossal
injection and can cause neuropathology and disease. IMPORTANCE: Synucleinopathies
are neurodegenerative diseases that are characterized by the pathological
presence of aggregated alpha-synuclein in cells of the nervous system. Previous
studies have shown that alpha-synuclein aggregates made of recombinant protein or
derived from brains of patients can spread in the central nervous system in a
spatiotemporal manner when inoculated into the brains of animals and can induce
pathology and neurologic disease, suggesting that misfolded alpha-synuclein can
behave similarly to prions. Here we show that alpha-synuclein inoculation into
the peritoneal cavity or the tongue in mice overexpressing alpha-synuclein causes
neurodegeneration after neuroinvasion from the periphery, which further
corroborates the prionoid character of misfolded alpha-synuclein.
PMID- 27489280
TI - Fungus-Derived Neoechinulin B as a Novel Antagonist of Liver X Receptor,
Identified by Chemical Genetics Using a Hepatitis C Virus Cell Culture System.
AB - Cell culture systems reproducing virus replication can serve as unique models for
the discovery of novel bioactive molecules. Here, using a hepatitis C virus (HCV)
cell culture system, we identified neoechinulin B (NeoB), a fungus-derived
compound, as an inhibitor of the liver X receptor (LXR). NeoB was initially
identified by chemical screening as a compound that impeded the production of
infectious HCV. Genome-wide transcriptome analysis and reporter assays revealed
that NeoB specifically inhibits LXR-mediated transcription. NeoB was also shown
to interact directly with LXRs. Analysis of structural analogs suggested that the
molecular interaction of NeoB with LXR correlated with the capacity to inactivate
LXR-mediated transcription and to modulate lipid metabolism in hepatocytes. Our
data strongly suggested that NeoB is a novel LXR antagonist. Analysis using NeoB
as a bioprobe revealed that LXRs support HCV replication: LXR inactivation
resulted in dispersion of double-membrane vesicles, putative viral replication
sites. Indeed, cells treated with NeoB showed decreased replicative
permissiveness for poliovirus, which also replicates in double-membrane vesicles,
but not for dengue virus, which replicates via a distinct membrane compartment.
Together, our data suggest that LXR-mediated transcription regulates the
formation of virus-associated membrane compartments. Significantly, inhibition of
LXRs by NeoB enhanced the activity of all known classes of anti-HCV agents, and
NeoB showed especially strong synergy when combined with interferon or an HCV
NS5A inhibitor. Thus, our chemical genetics analysis demonstrates the utility of
the HCV cell culture system for identifying novel bioactive molecules and
characterizing the virus-host interaction machinery. IMPORTANCE: Hepatitis C
virus (HCV) is highly dependent on host factors for efficient replication. In the
present study, we used an HCV cell culture system to screen an uncharacterized
chemical library. Our results identified neoechinulin B (NeoB) as a novel
inhibitor of the liver X receptor (LXR). NeoB inhibited the induction of LXR
regulated genes and altered lipid metabolism. Intriguingly, our results indicated
that LXRs are critical to the process of HCV replication: LXR inactivation by
NeoB disrupted double-membrane vesicles, putative sites of viral replication.
Moreover, NeoB augmented the antiviral activity of all known classes of currently
approved anti-HCV agents without increasing cytotoxicity. Thus, our strategy
directly links the identification of novel bioactive compounds to basic virology
and the development of new antiviral agents.
PMID- 27489281
TI - Human Choline Kinase-alpha Promotes Hepatitis C Virus RNA Replication through
Modulation of Membranous Viral Replication Complex Formation.
AB - Hepatitis C virus (HCV) infection reorganizes cellular membranes to create an
active viral replication site named the membranous web (MW). The role that human
choline kinase-alpha (hCKalpha) plays in HCV replication remains elusive. Here,
we first showed that hCKalpha activity, not the CDP-choline pathway, promoted
viral RNA replication. Confocal microscopy and subcellular fractionation of HCV
infected cells revealed that a small fraction of hCKalpha colocalized with the
viral replication complex (RC) on the endoplasmic reticulum (ER) and that HCV
infection increased hCKalpha localization to the ER. In the pTM-NS3-NS5B model,
NS3-NS5B expression increased the localization of the wild-type, not the inactive
D288A mutant, hCKalpha on the ER, and hCKalpha activity was required for
effective trafficking of hCKalpha and NS5A to the ER. Coimmunoprecipitation
showed that hCKalpha was recruited onto the viral RC presumably through its
binding to NS5A domain 1 (D1). hCKalpha silencing or treatment with CK37, an
hCKalpha activity inhibitor, abolished HCV-induced MW formation. In addition,
hCKalpha depletion hindered NS5A localization on the ER, interfered with NS5A and
NS5B colocalization, and mitigated NS5A-NS5B interactions but had no apparent
effect on NS5A-NS4B and NS4B-NS5B interactions. Nevertheless, hCKalpha activity
was not essential for the binding of NS5A to hCKalpha or NS5B. These findings
demonstrate that hCKalpha forms a complex with NS5A and that hCKalpha activity
enhances the targeting of the complex to the ER, where hCKalpha protein, not
activity, mediates NS5A binding to NS5B, thereby promoting functional membranous
viral RC assembly and viral RNA replication. IMPORTANCE: HCV infection
reorganizes the cellular membrane to create an active viral replication site
named the membranous web (MW). Here, we report that human choline kinase-alpha
(hCKalpha) acts as an essential host factor for HCV RNA replication. A fraction
of hCKalpha colocalizes with the viral replication complex (RC) on the
endoplasmic reticulum (ER) in HCV-infected cells. NS3-NS5B expression increases
ER localization of wild-type, but not D288A mutant, hCKalpha, and hCKalpha
activity facilitates the transport of itself and NS5A to the ER. Silencing or
inactivation of hCKalpha abrogates MW formation. Moreover, hCKalpha is recruited
by NS5A independent of hCKalpha activity, presumably through binding to NS5A D1.
hCKalpha activity then mediates the ER targeting of the hCKalpha-NS5A complex. On
the ER membrane, hCKalpha protein, per se, induces NS5A binding to NS5B, thereby
promoting membranous RC formation and viral RNA replication. Our study may
benefit the development of hCKalpha-targeted anti-HCV therapeutics.
PMID- 27489282
TI - Carcinoembryonic Antigen-Related Cell Adhesion Molecule 5 Is an Important Surface
Attachment Factor That Facilitates Entry of Middle East Respiratory Syndrome
Coronavirus.
AB - The spike proteins of coronaviruses are capable of binding to a wide range of
cellular targets, which contributes to the broad species tropism of
coronaviruses. Previous reports have demonstrated that Middle East respiratory
syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4
(DPP4) for cell entry. However, additional cellular binding targets of the MERS
CoV spike protein that may augment MERS-CoV infection have not been further
explored. In the current study, using the virus overlay protein binding assay
(VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5
(CEACAM5) as a novel cell surface binding target of MERS-CoV. CEACAM5
coimmunoprecipitated with the spike protein of MERS-CoV in both overexpressed and
endogenous settings. Disrupting the interaction between CEACAM5 and MERS-CoV
spike with anti-CEACAM5 antibody, recombinant CEACAM5 protein, or small
interfering RNA (siRNA) knockdown of CEACAM5 significantly inhibited the entry of
MERS-CoV. Recombinant expression of CEACAM5 did not render nonpermissive baby
hamster kidney (BHK21) cells susceptible to MERS-CoV infection. Instead, CEACAM5
overexpression significantly enhanced the attachment of MERS-CoV to the BHK21
cells. More importantly, the entry of MERS-CoV was increased when CEACAM5 was
overexpressed in permissive cells, which suggested that CEACAM5 could facilitate
MERS-CoV entry in conjunction with DPP4 despite not being able to support MERS
CoV entry independently. Taken together, the results of our study identified
CEACAM5 as a novel cell surface binding target of MERS-CoV that facilitates MERS
CoV infection by augmenting the attachment of the virus to the host cell surface.
IMPORTANCE: Infection with the Middle East respiratory syndrome coronavirus (MERS
CoV) is associated with the highest mortality rate among all known human
pathogenic coronaviruses. Currently, there are no approved vaccines or
therapeutics against MERS-CoV infection. The identification of carcinoembryonic
antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface
binding target of MERS-CoV advanced our knowledge on the cell binding biology of
MERS-CoV. Importantly, CEACAM5 could potentiate the entry of MERS-CoV by
functioning as an attachment factor. In this regard, CEACAM5 could serve as a
novel target, in addition to dipeptidyl peptidase-4 (DPP4), in the development of
antiviral strategies for MERS-CoV.
PMID- 27489284
TI - Leukotriene B4 Receptor 2 Is Critical for the Synthesis of Vascular Endothelial
Growth Factor in Allergen-Stimulated Mast Cells.
AB - Mast cells are among the principal effector cells in the pathogenesis of allergic
asthma. In allergic reactions, allergen (Ag)-induced cross-linking of IgE bound
to FcepsilonRI on mast cells results in the production of vascular endothelial
growth factor (VEGF), which is essential for the initiation and development of
the allergic response. Despite the central role of VEGF in allergic asthma, the
signaling events responsible for the production of VEGF remain unclear,
particularly in Ag-stimulated mast cells. In the present study, we observed that
blocking leukotriene B4 receptor 2 (BLT2) completely abrogated the production of
VEGF in Ag-stimulated bone marrow-derived mast cells (BMMCs). The synthesis of
BLT2 ligands (leukotriene B4 and 12(S)-hydroxyeicosatetraenoic acid) was also
required for VEGF production, suggesting a mediating role of an autocrine BLT2
ligands-BLT2 axis in the production of VEGF in mast cells. The NADPH oxidase 1
reactive oxygen species-NF-kappaB cascade is downstream of BLT2 during Ag
signaling to VEGF synthesis in mast cells. Furthermore, the level of VEGF
synthesis in genetically mast cell-deficient Kit(W/Wv) mice was significantly
lower than that in wild-type mice in the OVA-induced asthma model, suggesting
that mast cells play a critical role in the synthesis of VEGF in OVA-induced
allergic asthma. Importantly, VEGF production was restored to the levels observed
in wild-type mice after adoptive transfer of normal BMMCs into Kit(W/Wv) mice but
was not restored in BLT2(-/-) BMMC-reconstituted Kit(W/Wv) mice in the OVA
induced asthma model. Taken together, our results suggest that BLT2 expression in
mast cells is essential for the production of VEGF in OVA-induced allergic
asthma.
PMID- 27489283
TI - Rpl22 Loss Selectively Impairs alphabeta T Cell Development by Dysregulating
Endoplasmic Reticulum Stress Signaling.
AB - Although ribosomal proteins (RP) are thought to primarily facilitate biogenesis
of the ribosome and its ability to synthesize protein, emerging evidence suggests
that individual RP can perform critical regulatory functions that control
developmental processes. We showed previously that despite the ubiquitous
expression of the RP ribosomal protein L22 (Rpl22), germline ablation of Rpl22 in
mice causes a selective, p53-dependent block in the development of alphabeta, but
not gammadelta, T cell progenitors. Nevertheless, the basis by which Rpl22 loss
selectively induces p53 in alphabeta T cell progenitors remained unclear. We show
in this study that Rpl22 regulates the development of alphabeta T cells by
restraining endoplasmic reticulum (ER) stress responses. In the absence of Rpl22,
ER stress is exacerbated in alphabeta, but not gammadelta, T cell progenitors.
The exacerbated ER stress in Rpl22-deficient alphabeta T lineage progenitors is
responsible for selective induction of p53 and their arrest, as pharmacological
induction of stress is sufficient to induce p53 and replicate the selective block
of alphabeta T cells, and attenuation of ER stress signaling by knockdown of
protein kinase R-like ER kinase, an ER stress sensor, blunts p53 induction and
rescues development of Rpl22-deficient alphabeta T cell progenitors. Rpl22
deficiency appears to exacerbate ER stress by interfering with the ability of ER
stress signals to block new protein synthesis. Our finding that Rpl22 deficiency
exacerbates ER stress responses and induces p53 in alphabeta T cell progenitors
provides insight into how a ubiquitously expressed RP can perform regulatory
functions that are selectively required by some cell lineages but not others.
PMID- 27489285
TI - MAGE-C2-Specific TCRs Combined with Epigenetic Drug-Enhanced Antigenicity Yield
Robust and Tumor-Selective T Cell Responses.
AB - Adoptive T cell therapy has shown significant clinical success for patients with
advanced melanoma and other tumors. Further development of T cell therapy
requires improved strategies to select effective, yet nonself-reactive, TCRs. In
this study, we isolated 10 TCR sequences against four MAGE-C2 (MC2) epitopes from
melanoma patients who showed clinical responses following vaccination that were
accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor
without apparent side effects. We introduced these TCRs into T cells, pretreated
tumor cells of different histological origins with the epigenetic drugs
azacytidine and valproate, and tested tumor and self-reactivities of these TCRs.
Pretreatment of tumor cells upregulated MC2 gene expression and enhanced
recognition by T cells. In contrast, a panel of normal cell types did not express
MC2 mRNA, and similar pretreatment did not result in recognition by MC2-directed
T cells. Interestingly, the expression levels of MC2, but not those of CD80,
CD86, or programmed death-ligand 1 or 2, correlated with T cell responsiveness.
One of the tested TCRs consistently recognized pretreated MC2(+) cell lines from
melanoma, head and neck, bladder, and triple-negative breast cancers but showed
no response to MHC-eluted peptides or peptides highly similar to MC2. We conclude
that targeting MC2 Ag, combined with epigenetic drug-enhanced antigenicity,
allows for significant and tumor-selective T cell responses.
PMID- 27489286
TI - ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet-associated
Colon Cancer.
AB - PURPOSE: Epidermal growth factor receptors (EGFR) are required for tumor
promotion by Western diet. The metalloprotease, ADAM17 activates EGFR by
releasing pro-EGFR ligands. ADAM17 is regulated by G-protein-coupled receptors,
including CXCR4. Here we investigated CXCR4-ADAM17 crosstalk and examined the
role of ADAM17 in tumorigenesis. EXPERIMENTAL DESIGN: We used CXCR4 inhibitor,
AMD3100 and ADAM17 inhibitor, BMS566394 to assess CXCR4-ADAM17 crosstalk in colon
cancer cells. We compared the expression of CXCR4 ligand, CXCL2, and ADAM17 in
mice fed Western diet versus standard diet. Separately, mice were treated with
marimastat, a broad-spectrum ADAM17 inhibitor, or AMD3100 to assess EGFR
activation by ADAM17 and CXCR4. Using Apc-mutant Min mice, we investigated the
effects of ADAM17/10 inhibitor INCB3619 on tumorigenesis. To assess the effects
of colonocyte ADAM17, mice with ADAM17 conditional deletion were treated with
azoxymethane (AOM). ADAM17 expression was also compared in colonocytes from
primary human colon cancers and adjacent mucosa. RESULTS: CXCL12 treatment
activated colon cancer cell EGFR signals, and CXCR4 or ADAM17 blockade reduced
this activation. In vivo, Western diet increased CXCL12 in stromal cells and
TGFalpha in colonocytes. Marimastat or AMD3100 caused >50% reduction in EGFR
signals (P < 0.05). In Min mice, INCB3619 reduced EGFR signals in adenomas and
inhibited intestinal tumor multiplicity (P < 0.05). In the AOM model, colonocyte
ADAM17 deletion reduced EGFR signals and colonic tumor development (P < 0.05).
Finally, ADAM17 was upregulated >2.5-fold in human malignant colonocytes.
CONCLUSIONS: ADAM17 is a Western diet-inducible enzyme activated by CXCL12-CXCR4
signaling, suggesting the pathway: Western diet->CXCL12->CXCR4->ADAM17->TGFalpha
>EGFR. ADAM17 might serve as a druggable target in chemoprevention strategies.
Clin Cancer Res; 23(2); 549-61. (c)2016 AACR.
PMID- 27489288
TI - Antihypoxic Potentiation of Standard Therapy for Experimental Colorectal Liver
Metastasis through Myo-Inositol Trispyrophosphate.
AB - PURPOSE: Tumor hypoxia activates hypoxia-inducible factors (Hifs), which induce a
range of malignant changes including vascular abnormalities. Here, we determine
whether inhibition of the hypoxic tumor response through myo-inositol
trispyrophosphate (ITPP), a compound with antihypoxic properties, is able to
cause prolonged vascular normalization that can be exploited to improve standard
of-care treatment. EXPERIMENTAL DESIGN: We tested ITPP on two syngeneic
orthotopic mouse models of lethal colorectal cancer liver metastasis. Tumors were
monitored by MRI and analyzed for the hypoxic response and their malignant
potential. A Hif activator and in vitro assays were used to define the working
mode of ITPP. Hypoxic response and vasculature were re-evaluated 4 weeks after
treatment. Finally, we determined survival following ITPP monotherapy, FOLFOX
monotherapy, FOLFOX plus Vegf antibody, and FOLFOX plus ITPP, both overlapping
and sequential. RESULTS: ITPP reduced tumor load, efficiently inhibited the
hypoxic response, and improved survival. These effects were lost when mice were
pretreated with a Hif activator. Its immediate effects on the hypoxic response,
including an apparent normalization of tumor vasculature, persisted for at least
4 weeks after treatment cessation. Compared with FOLFOX alone, Vegf antibody
combined with FOLFOX prolonged survival by <30%, whereas ITPP combined with
FOLFOX extended survival by >140%, regardless of whether FOLFOX was given in
overlap or after ITPP exposure. CONCLUSIONS: Our findings reveal a truly
antihypoxic mechanism for ITPP and demonstrate the capacity of this nontoxic
compound to potentiate the efficacy of existing anticancer treatment in a way
amenable to clinical translation. Clin Cancer Res; 22(23); 5887-97. (c)2016 AACR.
PMID- 27489287
TI - Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival
in Patients with Metastatic Breast Cancer Receiving Taxane-Based Chemotherapy.
AB - PURPOSE: Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor
cancer outcomes, including reduced survival and increased toxicity. This study
investigates SM measures in metastatic breast cancer (MBC) patients receiving
first-line taxane-based chemotherapy and evaluates associations with treatment
toxicity and other outcomes. EXPERIMENTAL DESIGN: Using computerized tomography
(CT) images taken for the evaluation of disease burden, skeletal muscle area
(SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia
was defined as skeletal muscle index (SMI = SMA/height2) <= 41. Skeletal muscle
gauge (SMG) was created by multiplying SMI * SMD. Fisher exact tests, t tests,
the Kaplan-Meier method, and Cox regression modeling were used. RESULTS: MBC
patients (N = 40), median age 55 (range, 34-80), 58% sarcopenic, median SMG 1296
AU (SD, 522). Grade 3-4 toxicity was found in 57% of sarcopenic versus 18% of non
sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also
higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events
defined as any grade 3-4 toxicities, hospitalizations, dose reductions, or dose
delay-(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3-4 toxicity (P
= 0.04), hospitalization (P = 0.01), and time to treatment failure (for
progression or toxicity; P = 0.03). Low SMG had a borderline significant
association with any adverse event (P = 0.06) and overall survival (P = 0.07).
CONCLUSIONS: SM measures are associated with toxicity outcomes and survival in
MBC patients receiving first-line taxane-based chemotherapy. Further studies are
needed to explore how routinely obtained CT scans can be used to individualize
dosing and improve treatment planning. Clin Cancer Res; 23(3); 658-65. (c)2016
AACR.
PMID- 27489289
TI - Individualized Molecular Analyses Guide Efforts (IMAGE): A Prospective Study of
Molecular Profiling of Tissue and Blood in Metastatic Triple-Negative Breast
Cancer.
AB - PURPOSE: The clinical utility of next-generation sequencing (NGS) in breast
cancer has not been demonstrated. We hypothesized that we could perform NGS of a
new biopsy from patients with metastatic triple-negative breast cancer (TNBC) in
a clinically actionable timeframe. EXPERIMENTAL DESIGN: We planned to enroll 40
patients onto a prospective study, Individualized Molecular Analyses Guide
Efforts (IMAGE), to evaluate the feasibility of obtaining a new biopsy of a
metastatic site, perform NGS (FoundationOne), and convene a molecular tumor board
to formulate treatment recommendations within 28 days. We collected blood at
baseline and at time of restaging to assess cell-free circulating plasma tumor
DNA (ptDNA). RESULTS: We enrolled 26 women with metastatic TNBC who had received
>=1 line of prior chemotherapy, and 20 (77%) underwent NGS of a metastatic site
biopsy. Twelve (60%) evaluable patients received treatment recommendations within
28 days of consent. The study closed after 20 patients underwent NGS, based on
protocol-specified interim futility analysis. Three patients went on to receive
genomically directed therapies. Twenty-four of 26 patients had genetic
alterations successfully detected in ptDNA. Among 5 patients, 4 mutations found
in tumor tissues were not identified in blood, and 4 mutations found in blood
were not found in corresponding tumors. In 9 patients, NGS of follow-up blood
samples showed 100% concordance with baseline blood samples. CONCLUSIONS: This
study demonstrates challenges of performing NGS on prospective tissue biopsies in
patients with metastatic TNBC within 28 days, while also highlighting the
potential use of blood as a more time-efficient and less invasive method of
mutational assessment. Clin Cancer Res; 23(2); 379-86. (c)2016 AACR.
PMID- 27489292
TI - Systemic lupus erythematosus: not just a rash.
PMID- 27489291
TI - Cell-free Determination of Binary Complexes That Comprise Extended Protein
Protein Interaction Networks of Yersinia pestis.
AB - Binary protein interactions form the basic building blocks of molecular networks
and dynamic assemblies that control all cellular functions of bacteria. Although
these protein interactions are a potential source of targets for the development
of new antibiotics, few high-confidence data sets are available for the large
proteomes of most pathogenic bacteria. We used a library of recombinant proteins
from the plague bacterium Yersinia pestis to probe planar microarrays of
immobilized proteins that represented ~85% (3552 proteins) of the bacterial
proteome, resulting in >77,000 experimentally determined binary interactions.
Moderate (KD ~MUm) to high-affinity (KD ~nm) interactions were characterized for
>1600 binary complexes by surface plasmon resonance imaging of microarrayed
proteins. Core binary interactions that were in common with other gram-negative
bacteria were identified from the results of both microarray methods. Clustering
of proteins within the interaction network by function revealed statistically
enriched complexes and pathways involved in replication, biosynthesis, virulence,
metabolism, and other diverse biological processes. The interaction pathways
included many proteins with no previously known function. Further, a large
assembly of proteins linked to transcription and translation were contained
within highly interconnected subregions of the network. The two-tiered microarray
approach used here is an innovative method for detecting binary interactions, and
the resulting data will serve as a critical resource for the analysis of protein
interaction networks that function within an important human pathogen.
PMID- 27489290
TI - Association of AR-V7 and Prostate-Specific Antigen RNA Levels in Blood with
Efficacy of Abiraterone Acetate and Enzalutamide Treatment in Men with Prostate
Cancer.
AB - PURPOSE: We evaluated the association of PSA and androgen receptor splice variant
7 (AR-V7) transcript levels in patients' blood with time to treatment failure
(TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide
treatment in castration-resistant prostate cancer (CRPC) patients. EXPERIMENTAL
DESIGN: RNA levels of AR-V7 and PSA in peripheral blood collected before
treatment were quantified using droplet digital-PCR in retrospective cohorts
treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC.
Multivariable Cox regression adjusted for known prognostic factors was used for
analyses. RESULTS: PSA transcripts were detected in 57% of abiraterone acetate
treated patients and in 63% of enzalutamide-treated patients. PSA-positive
patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95%
confidence interval (CI) 1.26-4.10) and 2.60 (95% CI, 1.19-5.69); P = 0.006 and
0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients
with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate
and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P =
0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in
enzalutamide cohort). In multivariable models, the association with TTF remained
significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01-4.05; P
= 0.048), but statistically insignificant in the abiraterone acetate cohort. In
both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA
expression on OS; patients with detectable PSA transcripts and high AR-V7
predicted the poorest OS. CONCLUSIONS: PSA and AR-V7 transcripts in blood
potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or
enzalutamide treatment. If validated prospectively, their detection could be
facilitated without isolation of circulating tumor cells. Clin Cancer Res; 23(3);
726-34. (c)2016 AACR.
PMID- 27489293
TI - Non-accidental salt poisoning.
PMID- 27489294
TI - Communities need to be equal partners in determining whether research is
acceptable.
PMID- 27489295
TI - Health Care Maintenance for the Pediatric Patient With Inflammatory Bowel
Disease.
AB - Nearly one-quarter of patients with inflammatory bowel disease (IBD) are younger
than 20 years of age at diagnosis. Furthermore, the incidence of IBD in children
continues to increase. Nevertheless, variation in management exists within the
care of patients with IBD with regards to disease screening and preventive care.
A multidisciplinary approach that involves the general practitioner and pediatric
gastroenterologist is needed to routinely monitor growth, bone health, vitamin
and mineral deficiencies, vaccination status, and endoscopic surveillance. It is
also important to monitor for extraintestinal manifestations of IBD that may
affect the liver, joints, skin, and eyes. The purpose of this article is to
provide an updated overview of comprehensive care for pediatric patients with
IBD.
PMID- 27489296
TI - Communication Challenges in Neonatal Encephalopathy.
AB - BACKGROUND: Families must process complex information related to neonatal
encephalopathy and therapeutic hypothermia. METHODS: In this mixed methods study,
semi-structured interviews were performed with parents whose infants were
enrolled in an existing longitudinal cohort study of therapeutic hypothermia
between 2011 and 2014. RESULTS: Thematic saturation was achieved after 20
interviews. Parental experience of communicating with clinicians was
characterized by 3 principle themes. Theme 1 highlighted that a fragmented
communication process mirrored the chaotic maternal and neonatal course. Parents
often received key information about neonatal encephalopathy and therapeutic
hypothermia from maternal clinicians. Infant medical information was often given
to 1 family member (60%), who felt burdened by the responsibility to relay that
information to others. Families universally valued the role of the bedside nurse,
who was perceived as the primary source of communication for most (75%) families.
Theme 2 encompassed the challenges of discussing the complex therapy of
therapeutic hypothermia: families appreciated clinicians who used lay language
and provided written material, and they often felt overwhelmed by technical
information that made it hard to understand the "big picture" of their infant's
medical course. Theme 3 involved the uncertain prognosis after neonatal
encephalopathy. Parents appreciated specific expectations about their infant's
long-term development, and experienced long-term distress about prognostic
uncertainty. CONCLUSIONS: Communicating complex and large volumes of information
in the midst of perinatal crisis presents inherent challenges for both clinicians
and families. We identified an actionable set of communication challenges that
can be addressed with targeted interventions.
PMID- 27489297
TI - Stronger and More Vulnerable: A Balanced View of the Impacts of the NICU
Experience on Parents.
AB - For parents, the experience of having an infant in the NICU is often
psychologically traumatic. No parent can be fully prepared for the extreme stress
and range of emotions of caring for a critically ill newborn. As health care
providers familiar with the NICU, we thought that we understood the impact of the
NICU on parents. But we were not prepared to see the children in our own families
as NICU patients. Here are some of the lessons our NICU experience has taught us.
We offer these lessons in the hope of helping health professionals consider a
balanced view of the NICU's impact on families.
PMID- 27489298
TI - Sequential Acquisition of Anal Human Papillomavirus (HPV) Infection Following
Genital Infection Among Men Who Have Sex With Women: The HPV Infection in Men
(HIM) Study.
AB - BACKGROUND: The purpose of this study was to assess the risk of sequential
acquisition of anal human papillomavirus (HPV) infection following a type
specific genital HPV infection for the 9-valent vaccine HPV types and investigate
factors associated with sequential infection among men who have sex with women
(MSW). METHODS: Genital and anal specimens were available for 1348 MSW
participants, and HPV genotypes were detected using the Roche Linear Array assay.
Sequential risk of anal HPV infection was assessed using hazard ratios (HRs)
among men with prior genital infection, compared with men with no prior genital
infection, in individual HPV type and grouped HPV analyses. RESULTS: In
individual analyses, men with prior HPV 16 genital infections had a significantly
higher risk of subsequent anal HPV 16 infections (HR, 4.63; 95% confidence
interval [CI], 1.41-15.23). In grouped analyses, a significantly higher risk of
sequential type-specific anal HPV infections was observed for any of the 9 types
(adjusted HR, 2.80; 95% CI, 1.32-5.99), high-risk types (adjusted HR, 2.65; 95%
CI, 1.26, 5.55), and low-risk types (adjusted HR, 5.89; 95% CI, 1.29, 27.01).
CONCLUSIONS: MSW with prior genital HPV infections had a higher risk of a
subsequent type-specific anal infection. The higher risk was not explained by
sexual intercourse with female partners. Autoinoculation is a possible mechanism
for the observed association.
PMID- 27489299
TI - Human Papillomavirus Prevalence Among 88 Male Virgins Residing in Brazil, Mexico,
and the United States.
AB - This study determined the prevalence and risk factors for genital human
papillomavirus (HPV) detection among men who deny ever engaging in penetrative
sex. A questionnaire was administered to 4123 men from a cohort study of HPV
natural history. Genital exfoliated cells were collected and genotyped for 36 HPV
types. Eighty-eight men were classified as virgins. Log-binomial regression
models identified factors associated with genital HPV detection. The prevalence
of any and high-risk HPV types among 88 male virgins was 25.0% and 18.2%,
respectively. Age and smoking status were associated with HPV detection. Further
studies are needed to better understand the risk for HPV infection among male
virgins.
PMID- 27489300
TI - What Is the Correct Approach for Comparing GFR by Different Methods across Levels
of GFR?
PMID- 27489301
TI - Measurement Error as Alternative Explanation for the Observation that CrCl/GFR
Ratio is Higher at Lower GFR.
AB - BACKGROUND AND OBJECTIVES: Overestimation of GFR by urinary creatinine clearance
(CrCl) at lower levels of GFR has long been attributed to enhanced creatinine
secretion. However, this does not take into consideration the contribution of
errors in measured GFR (and CrCl) due to short-term biologic variability or test
imprecision. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed cross
sectional data among 1342 participants from the Chronic Renal Insufficiency
Cohort study with baseline measurement of GFR by iothalamate clearance (iGFR) and
CrCl by 24-hour urine collection. We examined the CrCl/iGFR ratio classified by
categories of iGFR and also by categories of CrCl. RESULTS: Overall, mean
CrCl/iGFR ratio was 1.13. CrCl/iGFR ratio was higher at lower iGFR categories. In
contrast, this ratio was lower at lower CrCl levels. We hypothesize these
relationships could be due to measurement error, which is bolstered by
replicating these trends in a simulation and modeling exercise in which there was
no variation in the ratio of CrCl/iGFR with true kidney function but taking into
account the effect of measurement error in both CrCl and iGFR (of magnitudes
previously described in the literature). In our simulated data, the observed
CrCl/iGFR ratio was higher at lower observed iGFR levels when patients were
classified by categories of observed iGFR. When the same patients were classified
by categories of observed CrCl, the observed CrCl/iGFR ratio was lower at lower
observed CrCl levels. CONCLUSIONS: The combined empirical and modeling results
suggest that measurement errors (in both CrCl and iGFR) should be considered as
an alternative explanation for the longstanding observation that the ratio of
CrCl to iGFR gets larger as iGFR decreases.
PMID- 27489302
TI - A misleading false-negative result of Pneumocystis real-time PCR assay due to a
rare punctual mutation: A French multicenter study.
AB - This article describes a previously unreported mutation at position 210 (C210T)
of the mitochondrial large subunit ribosomal RNA (mtLSUrRNA) gene of Pneumocystis
jirovecii, which led to a false-negative result of a real-time polymerase chain
reaction (PCR) assay. Since the aforementioned real-time PCR assay is widely used
in France, a French multicenter study was conducted to estimate the mutation
frequency and its potential impact on the routine diagnosis of Pneumocystis
pneumonia (PCP). Through analysis of data obtained from eight centers, the
mutation frequency was estimated at 0.28%. This low frequency should not call
into question the routine use of this PCR assay. Nonetheless, the occurrence of
the false-negative PCR result provides arguments for maintaining microscopic
techniques combined to PCR assays to achieve PCP diagnosis.
PMID- 27489303
TI - An in vitro model of granuloma-like cell aggregates substantiates early host
immune responses against Mycobacterium massiliense infection.
AB - Mycobacterium massiliense (M. mass), belonging to the M. abscessus complex, is a
rapidly growing mycobacterium that is known to cause tuberculous-like lesions in
humans. To better understand the interaction between host cells and M. mass, we
used a recently developed in vitro model of early granuloma-like cell aggregates
composed of human peripheral blood mononuclear cells (PBMCs). PBMCs formed
granuloma-like, small and rounded cell aggregates when infected by live M. mass
Microscopic examination showed monocytes and macrophages surrounded by
lymphocytes, which resembled cell aggregation induced by M. tuberculosis (M. tb).
M. mass-infected PBMCs exhibited higher expression levels of HLA-DR, CD86 and
CD80 on macrophages, and a significant decrease in the populations of CD4+ and
CD8+ T cells. Interestingly, low doses of M. mass were sufficient to infect
PBMCs, while active host cell death was gradually induced with highly increased
bacterial loads, reflecting host destruction and dissemination of virulent rapid
growing mycobacteria (RGM). Collectively, this in vitro model of M. mass
infection improves our understanding of the interplay of host immune cells with
mycobacteria, and may be useful for developing therapeutics to control bacterial
pathogenesis.
PMID- 27489305
TI - Progresses in developmental biology.
PMID- 27489306
TI - Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders
in Humans.
AB - Ever since the brain was identified as an insulin-sensitive organ, evidence has
rapidly accumulated that insulin action in the brain produces multiple behavioral
and metabolic effects, influencing eating behavior, peripheral metabolism, and
cognition. Disturbances in brain insulin action can be observed in obesity and
type 2 diabetes (T2D), as well as in aging and dementia. Decreases in insulin
sensitivity of central nervous pathways, i.e., brain insulin resistance, may
therefore constitute a joint pathological feature of metabolic and cognitive
dysfunctions. Modern neuroimaging methods have provided new means of probing
brain insulin action, revealing the influence of insulin on both global and
regional brain function. In this review, we highlight recent findings on brain
insulin action in humans and its impact on metabolism and cognition. Furthermore,
we elaborate on the most prominent factors associated with brain insulin
resistance, i.e., obesity, T2D, genes, maternal metabolism, normal aging,
inflammation, and dementia, and on their roles regarding causes and consequences
of brain insulin resistance. We also describe the beneficial effects of enhanced
brain insulin signaling on human eating behavior and cognition and discuss
potential applications in the treatment of metabolic and cognitive disorders.
PMID- 27489304
TI - Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required
for development and stress resilience.
AB - Stress granules are cytoplasmic foci that directly respond to the protein
synthesis status of the cell. Various environmental insults, such as oxidative
stress or extreme heat, block protein synthesis; consequently, mRNA will stall in
translation, and stress granules will immediately form and become enriched with
mRNAs. P54 DEAD box RNA helicases are components of RNA granules such as P-bodies
and stress granules. We studied the expression, in cytoplasmic foci, of both
zebrafish P54 RNA helicases (P54a and P54b) during development and found that
they are expressed in cytoplasmic granules under both normal conditions and
stress conditions. In zebrafish embryos exposed to heat shock, some proportion of
P54a and P54b helicases move to larger granules that exhibit the properties of
genuine stress granules. Knockdown of P54a and/or P54b in zebrafish embryos
produces developmental abnormalities restricted to the posterior trunk; further,
these embryos do not form stress granules, and their survival upon exposure to
heat-shock conditions is compromised. Our observations fit the model that cells
lacking stress granules have no resilience or ability to recover once the stress
has ended, indicating that stress granules play an essential role in the way
organisms adapt to a changing environment.
PMID- 27489307
TI - Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.
AB - Platelets are essential for physiological hemostasis and are central in
pathological thrombosis. These are their traditional and best known activities in
health and disease. In addition, however, platelets have specializations that
broaden their functional repertoire considerably. These functional capabilities,
some of which are recently discovered, include the ability to sense and respond
to infectious and immune signals and to act as inflammatory effector cells. Human
platelets and platelets from mice and other experimental animals can link the
innate and adaptive limbs of the immune system and act across the immune
continuum, often also linking immune and hemostatic functions. Traditional and
newly recognized facets of the biology of platelets are relevant to defensive,
physiological immune responses of the lungs and to inflammatory lung diseases.
The emerging view of platelets as blood cells that are much more diverse and
versatile than previously thought further predicts that additional features of
the biology of platelets and of megakaryocytes, the precursors of platelets, will
be discovered and that some of these will also influence pulmonary immune
defenses and inflammatory injury.
PMID- 27489308
TI - Copy-number variations are enriched for neurodevelopmental genes in children with
developmental coordination disorder.
AB - BACKGROUND: Developmental coordination disorder is a common neurodevelopment
disorder that frequently co-occurs with other neurodevelopmental disorders
including attention-deficit hyperactivity disorder (ADHD). Copy-number variations
(CNVs) have been implicated in a number of neurodevelopmental and psychiatric
disorders; however, the proportion of heritability in developmental coordination
disorder (DCD) attributed to CNVs has not been explored. OBJECTIVE: This study
aims to investigate how CNVs may contribute to the genetic architecture of DCD.
METHODS: CNV analysis was performed on 82 extensively phenotyped Canadian
children with DCD, with or without co-occurring ADHD and/or reading disorder, and
2988 healthy European controls using identical genome-wide SNP microarrays and
CNV calling algorithms. RESULTS: An increased rate of large and rare genic CNVs
(p=0.009) was detected, and there was an enrichment of duplications spanning
brain-expressed genes (p=0.039) and genes previously implicated in other
neurodevelopmental disorders (p=0.043). Genes and loci of particular interest in
this group included: GAP43, RBFOX1, PTPRN2, SHANK3, 16p11.2 and distal 22q11.2.
Although no recurrent CNVs were identified, 26% of DCD cases, where sample
availability permitted segregation analysis, were found to have a de novo rare
CNV. Of the inherited CNVs, 64% were from a parent who also had a
neurodevelopmental disorder. CONCLUSIONS: These findings suggest that there may
be shared susceptibility genes for DCD and other neurodevelopmental disorders and
highlight the need for thorough phenotyping when investigating the genetics of
neurodevelopmental disorders. Furthermore, these data provide compelling evidence
supporting a genetic basis for DCD, and further implicate rare CNVs in the
aetiology of neurodevelopmental disorders.
PMID- 27489309
TI - SERCA2 Deficiency Impairs Pancreatic beta-Cell Function in Response to Diet
Induced Obesity.
AB - The sarcoendoplasmic reticulum (ER) Ca(2+) ATPase 2 (SERCA2) pump is a P-type
ATPase tasked with the maintenance of ER Ca(2+) stores. Whereas beta-cell SERCA2
expression is reduced in diabetes, the role of SERCA2 in the regulation of whole
body glucose homeostasis has remained uncharacterized. To this end, SERCA2
heterozygous mice (S2HET) were challenged with a high-fat diet (HFD) containing
45% of kilocalories from fat. After 16 weeks of the HFD, S2HET mice were
hyperglycemic and glucose intolerant, but adiposity and insulin sensitivity were
not different between HFD-fed S2HET mice and HFD-fed wild-type controls.
Consistent with a defect in beta-cell function, insulin secretion, glucose
induced cytosolic Ca(2+) mobilization, and the onset of steady-state glucose
induced Ca(2+) oscillations were impaired in HFD-fed S2HET islets. Moreover, HFD
fed S2HET mice exhibited reduced beta-cell mass and proliferation, altered
insulin production and proinsulin processing, and increased islet ER stress and
death. In contrast, SERCA2 activation with a small molecule allosteric activator
increased ER Ca(2+) storage and rescued tunicamycin-induced beta-cell death. In
aggregate, these data suggest a critical role for SERCA2 and the regulation of ER
Ca(2+) homeostasis in the beta-cell compensatory response to diet-induced
obesity.
PMID- 27489310
TI - Partial Disruption of Lipolysis Increases Postexercise Insulin Sensitivity in
Skeletal Muscle Despite Accumulation of DAG.
AB - Type 2 diabetes and skeletal muscle insulin resistance have been linked to
accumulation of the intramyocellular lipid-intermediate diacylglycerol (DAG).
However, recent animal and human studies have questioned such an association.
Given that DAG appears in different stereoisomers and has different reactivity in
vitro, we investigated whether the described function of DAGs as mediators of
lipid-induced insulin resistance was dependent on the different DAG isomers. We
measured insulin-stimulated glucose uptake in hormone-sensitive lipase (HSL)
knockout (KO) mice after treadmill exercise to stimulate the accumulation of DAGs
in skeletal muscle. We found that, despite an increased DAG content in muscle
after exercise in HSL KO mice, the HSL KO mice showed a higher insulin-stimulated
glucose uptake postexercise compared with wild-type mice. Further analysis of the
chemical structure and cellular localization of DAG in skeletal muscle revealed
that HSL KO mice accumulated sn-1,3 DAG and not sn-1,2 DAG. Accordingly, these
results highlight the importance of taking the chemical structure and cellular
localization of DAG into account when evaluating the role of DAG in lipid-induced
insulin resistance in skeletal muscle and that the accumulation of sn-1,3 DAG
originating from lipolysis does not inhibit insulin-stimulated glucose uptake.
PMID- 27489311
TI - Micromachining and validation of the scanning acoustic microscope spatial
resolution and sensitivity calibration block for 20-230 MHz frequency range.
AB - Scanning acoustic microscopy (SAM) is used as a routine non-destructive test tool
for different diagnostic examinations: detection of defects such as microcracks,
delamination, disbonding, inclusions, subsurface features in materials such as
pores and cracks. SAM can be operated in a wide frequency range from Megahertz to
Gigahertz. SAM measurement spatial resolution is diffraction limited by the
wavelength of the acoustic wave in particular medium and also depends on
individual transducers geometry. Actual SAM spatial resolution can be determined
by measuring calibrated lithographically formed microstructures in high acoustic
impedance materials. Numerical acoustic signal simulation method, based on the
diffraction approach, was employed for the selection of the calibration block
pattern geometry and linear dimensions of the elements. Universal calibration
block for SAM operating in a 20-230 MHz frequency range was micromachined in high
acoustic impedance ceramic substrates. Differently spaced (from 18 to 185 um)
lines of the same width and different widths (from 17 to 113 um) but similar
spacing lines were imposed in alumina ceramics employing one step lithography
process, i.e. femtosecond laser ablation. Proposed SAM calibration pattern linear
dimensions were characterized employing optical and scanning electron microscopy.
Finally the samples were measured with SAM employing different frequency
transducers and results were compared with the numerical simulations. It was
obtained that resolution of SAM operating with 230 MHz transducer is not worse
than 40 um.
PMID- 27489313
TI - Persistence of Racial and Ethnic Differences in Utilization and Adverse Outcomes
of Total Joint Replacement.
PMID- 27489312
TI - Transcriptome Profiling of the Green Alga Spirogyra pratensis (Charophyta)
Suggests an Ancestral Role for Ethylene in Cell Wall Metabolism, Photosynthesis,
and Abiotic Stress Responses.
AB - It is well known that ethylene regulates a diverse set of developmental and
stress-related processes in angiosperms, yet its roles in early-diverging
embryophytes and algae are poorly understood. Recently, it was shown that
ethylene functions as a hormone in the charophyte green alga Spirogyra pratensis
Since land plants evolved from charophytes, this implies conservation of ethylene
as a hormone in green plants for at least 450 million years. However, the
physiological role of ethylene in charophyte algae has remained unknown. To gain
insight into ethylene responses in Spirogyra, we used mRNA sequencing to measure
changes in gene expression over time in Spirogyra filaments in response to an
ethylene treatment. Our analyses show that at the transcriptional level, ethylene
predominantly regulates three processes in Spirogyra: (1) modification of the
cell wall matrix by expansins and xyloglucan endotransglucosylases/hydrolases,
(2) down-regulation of chlorophyll biosynthesis and photosynthesis, and (3)
activation of abiotic stress responses. We confirmed that the photosynthetic
capacity and chlorophyll content were reduced by an ethylene treatment and that
several abiotic stress conditions could stimulate cell elongation in an ethylene
dependent manner. We also found that the Spirogyra transcriptome harbors only 10
ethylene-responsive transcription factor (ERF) homologs, several of which are
regulated by ethylene. These results provide an initial understanding of the
hormonal responses induced by ethylene in Spirogyra and help to reconstruct the
role of ethylene in ancestral charophytes prior to the origin of land plants.
PMID- 27489314
TI - Racial and Ethnic Disparities in Utilization Rate, Hospital Volume, and
Perioperative Outcomes After Total Knee Arthroplasty.
AB - BACKGROUND: Previous studies of racial disparities in total joint replacement,
particularly total knee arthroplasty, in the U.S. have predominantly focused on
disparities between blacks and whites and were limited to Medicare patients or
veterans, populations that are not representative of the entire U.S. POPULATION:
We sought to study racial disparities in the utilization of total knee
arthroplasty, the use of high-volume hospitals, and total knee arthroplasty
outcomes, including mortality and complications, using all-payer databases.
METHODS: We analyzed data from 8 years and 8 racially diverse states in the State
Inpatient Databases (SID). Patient race was categorized according to the SID as
white, black, Hispanic, Asian, Native American, and mixed race. Both crude and
adjusted racial and/or ethnic disparities were evaluated. RESULTS: In comparison
with whites (4.65 per 1000 population per year), black (3.90), Hispanic (3.71),
Asian (3.89), Native American (4.40), and mixed-race (3.69) populations had lower
rates of total knee arthroplasty utilization (p < 0.0001). After risk adjustment,
the rate of total knee arthroplasty utilization was significantly lower for
blacks (odds ratio [OR] = 0.87 [95% confidence interval (CI), 0.85 to 0.89]; p <
0.0001), Hispanics (OR = 0.76 [95% CI, 0.68 to 0.83]; p < 0.0001), Asians (OR =
0.83 [95% CI, 0.78 to 0.89]; p < 0.0001), Native Americans (OR = 0.87 [95% CI,
0.81 to 0.93]; p < 0.0001), and mixed race (OR = 0.84 [95% CI, 0.79 to 0.90]; p <
0.0001) compared with the rate for whites. Lower rates of total knee arthroplasty
utilization for blacks, Hispanics, and mixed-race groups became worse over the
years. Patients from minority groups were less likely to undergo total knee
arthroplasty in high-volume hospitals than were whites. Moreover, the rates of
mortality were significantly higher for blacks (OR = 1.52 [95% CI, 1.17 to 1.97];
p = 0.0017), Native Americans (OR = 6.52 [95% CI, 4.63 to 9.17]; p < 0.0001), and
mixed-race patients (OR = 4.35 [95% CI, 3.24 to 5.84]; p < 0.0001). Blacks (OR =
1.08 [95% CI, 1.01 to 1.15]; p = 0.01) and mixed-race patients (OR = 1.17 [95%
CI, 1.001 to 1.36]; p = 0.04) had higher rates of complications than whites.
CONCLUSIONS: Minorities had lower rates of total knee arthroplasty utilization
but higher rates of adverse health outcomes associated with the procedure, even
after adjusting for patient-related and health-care system-related
characteristics. Utilization rates were based on overall population as the
proportion of the population with osteoarthritis requiring arthroplasty is
unknown. Future studies that consider specific patient-level information with
psychosocial and behavioral factors are needed. LEVEL OF EVIDENCE: Prognostic
Level III. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 27489315
TI - The Effect of the Risser Stage on Bracing Outcome in Adolescent Idiopathic
Scoliosis.
AB - BACKGROUND: To determine the influence of the Risser sign on the need for surgery
in children wearing orthoses for the treatment of adolescent idiopathic scoliosis
(AIS), data on compliance with brace wear were collected and analyzed. METHODS:
One hundred and sixty-eight patients were prospectively enrolled at the time that
brace wear had been prescribed and were followed until the cessation of bracing
or the need for surgery. Inclusion criteria were a curve magnitude between 25
degrees and 45 degrees ; a Risser stage of 0, 1, or 2; and, if female, <1 year
post menarche at the time of brace prescription. Compliance was measured using
thermal monitors. RESULTS: The prevalence of surgery, or progression to a curve
magnitude of >=50 degrees , was 44.2% for patients at Risser stage 0 (n = 120),
6.9% for patients at Risser stage 1 (n = 29), and 0% for patients at Risser stage
2 (n = 19). Brace wear averaged 11.3, 13.4, and 14.2 hours per day for the Risser
stage-0, 1, and 2 groups, respectively. While the groups had no difference in
initial curve magnitude (p = 0.11), more patients at Risser stage 0 had
progression to surgery than did patients at Risser stage 1 or stage 2 despite
bracing (p < 0.0001). Twenty-six (41.9%) of 62 Risser stage-0 patients who wore
braces >=12.9 hours per day had progression to surgery. Ten patients at Risser
stage 0 with closed triradiate cartilage wore braces >=18 hours per day, and none
underwent surgery. In comparison, 7 of 10 patients at Risser stage 0 with open
triradiate cartilage and similar daily brace wear underwent surgery. Of 9
patients at Risser stage 0 with open triradiate cartilage who wore braces >=12.9
hours daily for curves measuring <30 degrees , 7 had a nonsurgical outcome.
CONCLUSIONS: Patients at Risser stage 0 are at risk for surgery despite brace
wear. In these patients, 12.9 hours of daily wear-the number of hours linked with
a successful outcome in the BRAIST (Bracing in Adolescent Idiopathic Scoliosis
Trial)-did not prevent surgery. Patients with open triradiate cartilage were at
highest risk, especially those with curves of >=30 degrees . Risser stage-0
patients should be prescribed a minimum of 18 hours of brace wear. Bracing should
be initiated for curves of <30 degrees in patients at Risser stage 0, especially
those with open triradiate cartilage. LEVEL OF EVIDENCE: Prognostic Level II. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 27489316
TI - The Importance of Sufficient Graft Material in Achieving Foot or Ankle Fusion.
AB - BACKGROUND: Nonunion, an important complication following foot and ankle
arthrodesis, causes substantial morbidity and disability. In patients undergoing
hindfoot and ankle arthrodesis, autogenous bone graft (autograft) or a suitable
alternative is often used to promote osseous fusion across the joint. This study
assessed the importance of adequate graft material in the fusion space to achieve
joint fusion during ankle and hindfoot arthrodesis. METHODS: This study used data
from a previously published clinical trial of grafting material (recombinant
human platelet-derived growth factor-BB with beta-tricalcium phosphate [rhPDGF
BB/beta-TCP] or autograft) for healing in hindfoot and ankle arthrodesis to
correlate the amount of graft fill at 9 weeks with ultimate healing. Patients who
received supplemental graft material for ankle or hindfoot arthrodesis for end
stage ankle or hindfoot arthritis were stratified according to nonunion risk
factors and surgical fusion site. Patients underwent arthrodesis using standard
rigid internal fixation. Graft fill was defined as "adequate" if the material
occupied >=50% of the cross-sectional area of the fusion space on a computed
tomography (CT) scan made at 9 weeks. Fusion was defined as osseous bridging of
>=50% of each articulation on a CT scan made at 24 weeks. Three hundred and
seventy-nine patients with 573 joints (383 managed with rhPDGF-BB/beta-TCP and
190 managed with autograft) that underwent arthrodesis had complete follow-up
with 9-week and 24-week CT scans available. RESULTS: Overall, 472 (82%) of 573
joints had adequate graft fill; of those, 383 (81%) were successfully fused at 24
weeks compared with 21 (21%) of 101 joints without adequate graft fill (p <
0.0001). Absolute fusion rate differences (joints with adequate fill minus those
without adequate fill) were consistent across joints (61% to 63%) and for graft
materials. The overall odds ratio (OR) of successful fusion in joints with
adequate graft fill compared with those without adequate graft fill was 16.4 (95%
confidence interval, 9.6 to 27.9). CONCLUSIONS: This study demonstrates an
association between the amount of graft material and successful hindfoot and
ankle arthrodesis. Graft material filling of >=50% of the fusion space at 9
weeks, regardless of type or origin, was associated with significantly higher
fusion rates at 24 weeks. LEVEL OF EVIDENCE: Therapeutic Level II. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 27489317
TI - Arthroscopic Lateral Collateral Ligament Repair.
AB - BACKGROUND: Lateral ulnar collateral ligament injury following unstable elbow
dislocation can induce posterolateral rotatory instability that requires surgery.
The aim of this study was to determine the effectiveness of arthroscopic repair
of the lateral collateral ligament (LCL) complex in an unstable elbow joint.
METHODS: The study group consisted of 13 patients who experienced posterolateral
rotatory instability after an unstable elbow dislocation with an injury to the
lateral ulnar collateral ligament. The diagnosis was confirmed with computed
tomography (CT), magnetic resonance imaging (MRI), and physical examination. The
patients underwent arthroscopically assisted surgery between May 2011 and January
2013 and were followed for a minimum of 18 months postoperatively. Coronoid
and/or radial head fractures combined with the ligament injury were treated
through an arthroscopic technique. Range of motion, pain, outcomes according to
the Mayo Elbow Performance Score (MEPS) and Nestor grading system, and surgical
complications were evaluated. CT and MRI were performed at 3 months
postoperatively, and isometric muscle strength was measured at the time of final
follow-up. RESULTS: At the time of final follow-up, at a minimum of 18 months,
all 13 patients reported complete resolution of the instability and average (and
standard deviation) extension of 3 degrees +/- 1 degrees , flexion of 138
degrees +/- 6 degrees , supination of 88 degrees +/- 5 degrees , and pronation
of 87 degrees +/- 6. The mean MEPS was 92 points and, according to this
validated outcome score, the results were rated as excellent in 12 patients and
good in 1 patient. According to the Nestor grading system, the results were rated
as excellent in 11 patients and good in 2. Complete healing was seen on the 3
month follow-up MRI in 12 patients; however, 1 patient had mild widening of the
radiocapitellar joint space with incomplete healing but no instability symptoms.
All patients demonstrated normal strength on elbow flexion, extension, pronation,
and supination at the final follow-up visit. CONCLUSIONS: Arthroscopic repair of
the LCL complex in patients with posterolateral rotatory instability after an
unstable elbow dislocation, with or without an intra-articular fracture, is an
alternative treatment option for restoring elbow stability and achieving
satisfactory clinical and radiographic results. LEVEL OF EVIDENCE: Therapeutic
Level IV. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 27489318
TI - The Long-Term Outcome After Varus Derotational Osteotomy for Legg-Calve-Perthes
Disease: A Mean Follow-up of 42 Years.
AB - BACKGROUND: Varus derotational osteotomy (VDRO) is one of the most common
surgical treatments for Legg-Calve-Perthes disease, yet its long-term results
have not been fully assessed. We aimed to determine the long-term clinical and
radiographic outcomes following VDRO. METHODS: Forty patients (43 hips) who
underwent VDRO for Legg-Calve-Perthes disease at our institution from 1959 to
1983, and participated in a follow-up study completed 10 years earlier, were
approached for the present study. Clinical examination and radiographs were
evaluated. Hip status and well-being were assessed with the Harris hip score and
the Short Form-36 (SF-36). RESULTS: Thirty-five patients (37 hips) participated
in the study. Information regarding the need for an arthroplasty was gathered on
4 additional hips from the previous study. The mean follow-up was 42.5 years
(range, 32.4 to 56.5 years), with a mean patient age of 50.2 years (range, 35.9
to 67.8 years). In total, 7 patients (7 hips; 17% of 41 hips for which
information was available, including 1 hip from the original cohort of 40
patients [43 hips]), underwent a total hip arthroplasty for hip pain. Excluding
patients who had undergone an arthroplasty, the mean Harris hip and SF-36 scores
were 79.8 points (range, 23.1 to 100 points) and 74.8 (range, 15.1 to 100),
respectively. Twenty (64.5%) of the 31 hips that had not been replaced achieved a
good or excellent Harris hip score (>=80 points). Sixteen (57.1%) of 28 hips with
follow-up radiographs had no, or minimal, signs of osteoarthritis. The Stulberg
classification was associated with the Harris hip score, the SF-36 score, hip
pain, a Trendelenburg sign, coxa magna, and the Tonnis grade. In a multivariate
analysis, the Stulberg classification was the only factor associated with fair or
poor outcomes (a Harris hip score of <80 points). Patients with a Stulberg class
III or IV hip had significant deterioration with respect to the Harris hip score
and Tonnis grade during the 10-year period since the last follow-up. CONCLUSIONS:
A long-term follow-up of patients who were operatively treated for Legg-Calve
Perthes disease revealed that a low proportion underwent total hip arthroplasty
and a relatively high proportion maintained good clinical and radiographic
outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
for a complete description of levels of evidence.
PMID- 27489319
TI - Midterm Results of Porous Tantalum Femoral Cones in Revision Total Knee
Arthroplasty.
AB - BACKGROUND: Severe bone loss during a revision total knee arthroplasty (TKA)
remains a challenging problem. The purpose of this study was to determine the
midterm clinical outcomes, fixation as evaluated radiographically, and
survivorship of tantalum femoral cones used during revision TKAs in patients with
severe femoral bone loss. METHODS: From 2003 to 2011, 159 tantalum metaphyseal
femoral cones were implanted in 157 patients at a single institution. Knee
Society scores, radiographic results, and implant survivorship were analyzed. Two
patients were lost to follow-up. Nineteen died of causes unrelated to the surgery
but had been followed for >2 years and thus were included in the study. The mean
age at the time of the index surgery was 64 years, and 82 patients were male. The
mean duration of follow-up was 5 years (range, 2 to 10 years). RESULTS: The mean
Knee Society score increased from 47 preoperatively to 65 at the most recent
follow-up evaluation (p = 0.1). Radiographically, all 134 unrevised femoral cones
were seen to be well fixed without any evidence of loosening. At 5 years, 23
cones had been revised: 14 because of infection, 6 because of aseptic loosening
of the cone (all in hinged TKAs in patients with a Type-3 defect), and 3 because
of ligamentous instability. The 5-year survivorship was 96% when the end point
was revision of the cone due to aseptic loosening, 84% when it was revision of
the cone for any reason, and 70% when it was any reoperation. CONCLUSIONS: In
what we believe to be the largest series of such implants, femoral cones provided
a durable and reliable option for metaphyseal fixation during revision TKA with
severe femoral bone loss. Aseptic failure of the femoral cone was associated with
use of a hinged TKA in a patient with a Type-3 bone defect. LEVEL OF EVIDENCE:
Therapeutic Level IV. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 27489320
TI - Risk Factors for Deep Infection Following Plate Fixation of Proximal Tibial
Fractures.
AB - BACKGROUND: The risk factors are unclear for deep surgical site infection after
plate fixation of proximal tibial fractures. The objective of this study was to
identify the patient and surgical procedure-related risk factors for infection
using established criteria for deep surgical site infection. METHODS: A total of
655 proximal tibial fractures were treated with open reduction and plate fixation
at our center between 2004 and 2013. We identified 34 patients with deep surgical
site infection. A control group of 136 patients was randomly selected from the
non-infected cohort. Potential risk factors for deep surgical site infection were
identified by reviewing surgical, medical, and radiographic records. Independent
risk factors for infection were identified from multivariable logistic regression
analysis using a stepwise procedure. RESULTS: The prevalence of deep surgical
site infection was 5.2%, the mean age of affected patients was 55 years (range,
16 to 84 years), and 35% of patients were female. Twenty-eight of 34 deep
infections were diagnosed within 2 months (acute onset), and only 6 infections
were diagnosed >6 months after the index surgical procedure. Nine of the 28 acute
onset infections were treated with antibiotic therapy and debridement. Seventeen
patients (50%) required muscle flap coverage, and 5 patients (15%) eventually
required above-the-knee amputation. In the multivariable logistic regression
analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs),
independent predictors of infection were patient age of >=50 years (OR, 3.6 [95%
CI, 1.3 to 10.1]); obesity, defined as a body mass index of >=30 kg/m(2) (OR, 6.5
[95% CI, 2.2 to 18.9]); alcohol abuse (OR, 6.7 [95% CI, 2.4 to 19.2]); OTA/AO
type-C fracture (OR, 2.8 [95% CI, 1.1 to 7.5]); use of a temporary spanning
external fixator (OR, 3.9 [95% CI, 1.4 to 11.1]); and a 4-compartment fasciotomy
(OR, 4.5 [95% CI, 1.3 to 15.7]). CONCLUSIONS: There is high morbidity associated
with deep surgical site infection in plated proximal tibial fractures. Patients
who are >=50 years of age, obese patients, those with a history of alcohol abuse,
or those with an OTA/AO-type-C fracture are at high risk for infection.
Performing a fasciotomy also increases the risk of deep infection and should be
implemented with meticulous technique when deemed necessary. LEVEL OF EVIDENCE:
Prognostic Level III. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 27489321
TI - The Rotterdam Foot Classification: A Classification System for Medial Polydactyly
of the Foot.
AB - BACKGROUND: Polydactyly at the medial side of the foot ("medial polydactyly" of
the foot) is a rare and diverse congenital anomaly. In order to plan and evaluate
surgical treatment, the classification of medial polydactyly is useful. The aim
of our study was to develop a reliable and valid classification system for medial
polydactyly of the foot that is more useful than previous systems for
preoperative evaluation and surgical planning. METHODS: A review of the
literature and the clinical experience of a single experienced surgeon were used
to determine classification categories. We identified all patients with medial
polydactyly who had preoperative radiographs and clinical photographs and were
treated at our hospital between 1993 and 2014. All affected feet were assessed
according to our proposed classification system, the Rotterdam foot
classification. The intrarater and interrater reliability among 5 observers who
evaluated 30 feet were assessed with use of the Cohen kappa (kappa) statistic.
RESULTS: We developed a classification system that describes duplication type,
syndactyly, the presence of a hypoplastic ray, and deviation of the hallux.
Seventy-three feet were classified according to the system. Seven duplication
types were distinguished. Complete metatarsal duplication was most frequently
seen (in 29%). Twelve feet showed a broad hallux without external expression of
duplication. Syndactyly between medial and lateral (duplicate) halluces was
present in 30 feet; between the lateral hallux and second toe, in 13 feet; and
between both duplicated halluces and the lateral hallux and second toe, in 21
feet. A hypoplastic ray was seen in 75% of the feet. Intrarater agreement for
duplication, hypoplastic rays, syndactyly, and deviation were, respectively,
kappa = 0.79, 0.75, 0.59, and 0.78. Interrater agreement for duplication,
hypoplastic rays, syndactyly, and deviation were, respectively, kappa = 0.72,
0.54, 0.48, and 0.64. CONCLUSIONS: The proposed classification system contains 4
categories of anatomic features of the foot. Classification of all categories
shows moderate to good reliability. Use of the Rotterdam classification in
evaluating medial polydactyly improves type-specific description, which may, in
the future, enhance the evaluation of surgical treatment. CLINICAL RELEVANCE: The
Rotterdam foot classification system is a reliable and easy-to-use system that we
believe will improve communication between clinicians and researchers and
facilitate the evaluation of treatment results in medial polydactyly of the foot.
PMID- 27489322
TI - Morphology and Prevalence Study of Lumbar Scoliosis in 7,075 Multiracial Asian
Adults.
AB - BACKGROUND: Lumbar scoliosis affects patients' quality of life and will
increasingly burden the health-care system as the population ages, yet there have
been few reports of its prevalence in Asians. The aim of this study was to
identify the prevalence of scoliosis, curve characteristics, and risk factors for
development of scoliosis in an Asian population. METHODS: A retrospective cross
sectional study was conducted using spinal images obtained from dual x-ray
absorptiometry (DXA) scans of individuals >=40 years of age. Scoliosis was
defined as a curvature of >10 degrees . A multivariate analysis for risk factors
for development of lumbar scoliosis was performed. RESULTS: Of 7,075 patients
studied, 645 (9.1%) were identified as having scoliosis. The average age of the
patients with scoliosis was 61 years (range, 40 to 98 years). The mean curve
prevalence was 9.4% in women and 6.5% in men. The average Cobb angle was 16.5
degrees (range, 10 degrees to 66 degrees ). Multivariate analysis showed an
increased risk of scoliosis in women (relative risk [RR] = 2.4, 95% CI =1.4 to
4.3), Chinese patients (RR = 2.4, 95% CI = 1.4 to 4.3), Malay patients (RR = 2.5,
95% CI = 1.3 to 4.9), and patients with spinal fracture (RR = 5.1, 95% CI = 3.0
to 8.8). The risk of scoliosis was found to increase as patients progressed
through each decade of life after the age of 40 years (6th decade: RR = 1.6, 95%
CI = 1.1 to 2.4, p = 0.026; 7th decade: RR = 2.7, 95% CI = 1.8 to 4.1, p < 0.001;
8th decade: RR = 5.0, 95% CI = 3.2 to 7.9, p < 0.001; and 9th decade: RR = 8.8,
95% CI = 4.3 to 17.9, p < 0.001). CONCLUSIONS: The prevalence of lumbar scoliosis
in Asian adults was found to be 9.1%. A nearly exponential increase in scoliosis
prevalence from the 5th decade of life (4%) to the >=9th decade (25%) and a
majority of left-sided scoliotic curves, measuring between 10 degrees and 19
degrees with an L2 apex, was found. Older age, female sex, Chinese or Malay
race, and vertebral fracture increased the risk of scoliosis developing. LEVEL OF
EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 27489323
TI - Positive Culture During Reimplantation Increases the Risk of Subsequent Failure
in Two-Stage Exchange Arthroplasty.
AB - BACKGROUND: It is strongly recommended that tissue and synovial fluid culture
samples be obtained during reimplantation performed as part of a 2-stage exchange
arthroplasty. The rate of positive cultures during reimplantation and the
influence of positive cultures on subsequent outcomes, to our knowledge, are
unknown. This study was designed to determine the rate of positive cultures
during reimplantation and to investigate the association between positive
cultures at reimplantation and subsequent outcomes. METHODS: We retrospectively
reviewed the data of 259 patients who met the Musculoskeletal Infection Society
criteria for periprosthetic joint infection (PJI) and who underwent both stages
of 2-stage exchange arthroplasty at our institution from 1999 to 2013. Among
these patients were 267 PJIs (186 knees and 81 hips); 33 (12.4%) had >=1 positive
culture result at reimplantation. Treatment failure was assessed according to the
Delphi-based consensus definition. Logistic regression analysis was performed to
assess the predictors of positive culture and risk factors for failure of 2-stage
exchange arthroplasty. RESULTS: Of the 33 cases with PJI, 15 (45.5%) had a
subsequent failure of the 2-stage exchange arthroplasty compared with 49 (20.9%)
of the cases that were culture-negative at reimplantation. When controlling for
other variables using multivariate analyses, the risk of treatment failure was
higher (odds ratio = 2.53; 95% confidence interval [CI] = 1.13 to 5.64) and
reinfection occurred earlier (hazard ratio = 2.00; 95% CI = 1.05 to 3.82) for the
cases with a positive culture during reimplantation. The treatment failure rate
did not differ (p = 0.73) between cases with >=2 positive cultures (36.4%) and 1
positive culture (50%). CONCLUSIONS: Positive intraoperative culture at the time
of reimplantation, regardless of the number of positive samples, was
independently associated with >2 times the risk of subsequent treatment failure
and earlier reinfection. Surgeons should be aware that a positive culture at the
time of reimplantation independently increases the risk of subsequent failure.
LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a
complete description of levels of evidence.
PMID- 27489324
TI - Advances in 3D-Printed Pediatric Prostheses for Upper Extremity Differences.
AB - ?The prohibitive cost of cutting-edge prostheses prevents many children with a
limb difference from obtaining them; however, new developments in 3-dimensional
(3D) printing have the potential to increase the accessibility, customization,
and procurement of such devices.?Children with upper limb differences are ideal
candidates for currently available 3D-printed devices because they quickly damage
and outgrow prostheses, and the low cost of 3D printing makes repairs and
upgrades substantially more affordable.?Physicians and medical practitioners
should become familiar with the possibilities of 3D-printed devices in order to
determine the benefits and utility for their patients.
PMID- 27489325
TI - Cartilage-Repair Innovation at a Standstill: Methodologic and Regulatory Pathways
to Breaking Free.
AB - Articular cartilage defects strongly predispose patients to developing early
joint degeneration and osteoarthritis, but for more than 15 years, no new
cartilage-repair technologies that we know of have been approved by the U.S. Food
and Drug Administration. Many studies examining novel approaches to cartilage
repair, including cell, tissue, or matrix-based techniques, have shown great
promise, but completing randomized controlled trials (RCTs) to establish safety
and efficacy has been challenging, providing a major barrier to bringing these
innovations into clinical use. In this article, we review reasons that surgical
innovations are not well-suited for testing through RCTs. We also discuss how
analytical methods for reducing bias, such as propensity scoring, make
prospective observational studies a potentially viable alternative for testing
the safety and efficacy of cartilage-repair and other novel therapies, offering
the real possibility of therapeutic innovation.
PMID- 27489326
TI - A 5-Year Update on the Uneven Distribution of Women in Orthopaedic Surgery
Residency Training Programs in the United States.
AB - BACKGROUND: This study was undertaken to update our report from academic years
2004-2005 through 2008-2009, to include 5 additional years of the Association of
American Medical Colleges GME Track data. This study will test the hypothesis
that, when compared with the data from 2004-2005 through 2008-2009, there were no
substantial changes from 2009-2010 through 2013-2014 in the distribution of
orthopaedic surgery residency programs that train female residents and have been
accredited by the Accreditation Council for Graduate Medical Education (ACGME).
METHODS: Data for all ACGME-accredited orthopaedic surgery residency training
programs in the United States were analyzed for 2009-2010 through 2013-2014, in
the same manner as our previous report analyzed data for 2004-2005 through 2008
2009. Programs were classified as having 0, 1, 2, or >2 women in training (i.e.,
for postgraduate year [PGY]-1 through PGY-5) for each of the 5 academic years.
Programs were also analyzed for the percentage of female residents in training
and were classified as being above the national average (>20%), similar to the
national average (between 10% and 20%), or below the national average (<10%) for
each of the 5 academic years. RESULTS: During the time period of 2004 to 2009,
the mean percentage of female trainees in U.S. orthopaedic surgery residency
programs was 11.6%, and during the time period of 2009 to 2014, this mean
percentage increased to 12.6%. Residency programs in the United States do not
train women at an equal rate. In the 5 years examined (2009 to 2014), 30 programs
had no female trainees and 49 programs had >20% women enrolled in at least 1 of
the 5 years, 8 programs had no female trainees enrolled in any of the 5 years,
and 9 programs had >20% women enrolled in each of the 5 years. CONCLUSIONS:
Female medical students continue to pursue orthopaedic surgery as a career at
rates lagging behind all other surgical specialties. Not all residency programs
train women at equal rates. The period of 2009-2010 through 2013-2014 showed a
greater percentage of programs (68%) training >=2 women than the period of 2004
2005 through 2008-2009 (61%). Obstacles to attracting women to orthopaedic
surgery should continue to be identified and to be addressed.
PMID- 27489327
TI - Adolescent Idiopathic Scoliosis: Immaturity Predicts Progression, but Is More
Brace Wear Time Beneficial? Commentary on an article by Lori A. Karol, MD, et
al.: "The Effect of the Risser Stage on Bracing Outcome in Adolescent Idiopathic
Scoliosis".
PMID- 27489328
TI - Please Teach Us More! Commentary on an article by G. David Potter III, MD, et
al.: "Midterm Results of Porous Tantalum Femoral Cones in Revision Total Knee
Arthroplasty".
PMID- 27489329
TI - Cutaneous Disease as the First Manifestation of Cystic Echinococcosis.
PMID- 27489332
TI - Questioning the Effectiveness of Oral Cholera Vaccine in Port-au-Prince Slums.
PMID- 27489333
TI - In Response.
PMID- 27489334
TI - hs-CRP Predicts Improvement in Depression in Patients With Type 1 Diabetes and
Major Depression Undergoing Depression Treatment: Results From the Diabetes and
Depression (DAD) Study.
PMID- 27489335
TI - Longitudinal Associations of Exposure to Perfluoroalkylated Substances in
Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6
and 12 Years Later: The European Youth Heart Study.
AB - OBJECTIVE: To investigate the long-term association of exposure to
perfluoroalkylated substances, including perfluorooctanesulfonic acid (PFOS) and
perfluorooctanoic acid (PFOA), during childhood (9 years) and adolescence (15
years) on indicators of adiposity and glucose metabolism in adolescence (15
years) and young adulthood (21 years). Secondarily, we aim to clarify the degree
of tracking of exposure from childhood into young adulthood. RESEARCH DESIGN AND
METHODS: Data derived from a large multicenter prospective cohort study, in which
the same participants have been observed from childhood (N = 590), during
adolescence (N = 444), and into young adulthood (N = 369). Stored plasma samples
were analyzed for PFOS and PFOA. Indicators of adiposity comprising body height,
body weight, sum of four skinfolds, and waist circumference, as well as
indicators of glucose metabolism, comprising fasting blood glucose, triglyceride,
and insulin levels, beta-cell function, and insulin resistance, have been
collected at all study waves. Multiple linear regression was applied in order to
model earlier exposure on later outcome while controlling for baseline outcome
levels, sex, age, and socioeconomic factors. RESULTS: Childhood exposure to PFOS
was associated with indicators of adiposity at 15 years of age that are displayed
in elevated BMI, skinfold thickness, and waist circumference, as well as
increased skinfold thickness and waist circumference at 21 years of age. PFOA
exposure in childhood was associated with decreased beta-cell function at 15
years of age. We did not observe associations between exposure during adolescence
and indicators of adiposity and glucose metabolism in young adulthood.
CONCLUSIONS: This study found evidence for childhood exposure to PFOS and PFOA
predicting adiposity at 15 and 21 years of age and impaired beta-cell function at
15 years of age, respectively.
PMID- 27489336
TI - Discordance Between Central (Brain) and Pancreatic Action of Exenatide in Lean
and Obese Subjects.
AB - OBJECTIVE: This study examined the effect of exenatide on brain activity measured
by functional (f)MRI and on insulin secretion in lean and obese normal-glucose
tolerant individuals. RESEARCH DESIGN AND METHODS: The brain fMRI signal in
response to high-calorie-content food pictures was measured with and without
intravenous exenatide infusion in 10 lean and 10 obese healthy volunteers.
Insulin secretion was measured with a two-step (+100 and +200 mg/dL)
hyperglycemic clamp with exenatide and with saline infusion. RESULTS: The brain
fMRI signal in response to food pictures in amygdala, insula, hippocampus, and
frontal cortex was significantly greater in obese versus lean individuals.
Intravenous exenatide significantly inhibited the fMRI signal in response to food
pictures in obese individuals but did not affect the brain fMRI signal in lean
subjects. Conversely, exenatide infusion caused an 18.5-fold increase in insulin
secretion in lean individuals compared with an 8.8-fold increase in obese
subjects. No significant correlation was observed between inhibition of the brain
fMRI signal and increase in insulin secretion during exenatide infusion.
CONCLUSIONS: Exenatide causes greater augmentation in insulin secretion in lean
compared with obese individuals but inhibits the brain response to food pictures
only in obese individuals.
PMID- 27489337
TI - Subjects With Extreme-Duration Type 1 Diabetes Exhibit No Structural or
Functional Abnormality on Cardiac MRI.
PMID- 27489338
TI - Transient endoreplication down-regulates the kinesin-14 HSET and contributes to
genomic instability.
AB - Polyploid cancer cells exhibit chromosomal instability (CIN), which is associated
with tumorigenesis and therapy resistance. The mechanisms that induce polyploidy
and how these mechanisms contribute to CIN are not fully understood. Here we
evaluate CIN in human cells that become polyploid through an experimentally
induced endoreplication cycle. When these induced endoreplicating cells (iECs)
returned to mitosis, it resulted in aneuploidy in daughter cells. This aneuploidy
resulted from multipolar divisions, chromosome missegregation, and failure in
cytokinesis. The iECs went through several rounds of division, ultimately
spawning proliferative cells of reduced ploidy. iECs have reduced levels of the
kinesin-14 HSET, which likely accounts for the multipolar divisions, and
overexpression of HSET reduced spindle multipolarity. However, HSET
overexpression had only mild effects on CIN, suggesting that additional defects
must contribute to genomic instability in dividing iECs. Overall our results
suggest that transient endoreplication cycles generate a diverse population of
proliferative aneuploid cells that have the potential to contribute to tumor
heterogeneity.
PMID- 27489339
TI - The sequential activation of the mitotic microtubule assembly pathways favors
bipolar spindle formation.
AB - Centrosome maturation is the process by which the duplicated centrosomes recruit
pericentriolar components and increase their microtubule nucleation activity
before mitosis. The role of this process in cells entering mitosis has been
mostly related to the separation of the duplicated centrosomes and thereby to the
assembly of a bipolar spindle. However, spindles can form without centrosomes. In
fact, all cells, whether they have centrosomes or not, rely on chromatin-driven
microtubule assembly to form a spindle. To test whether the sequential activation
of these microtubule assembly pathways, defined by centrosome maturation and
nuclear envelope breakdown, plays any role in spindle assembly, we combined
experiments in tissue culture cells and Xenopus laevis egg extracts with a
mathematical model. We found that interfering with the sequential activation of
the microtubule assembly pathways compromises bipolar spindle assembly in tissue
culture cells but not in X. laevis egg extracts. Our data suggest a novel
function for centrosome maturation that determines the contribution of the
chromosomal microtubule assembly pathway and favors bipolar spindle formation in
most animal cells in which tubulin is in limiting amounts.
PMID- 27489340
TI - Loss of Galpha12/13 exacerbates apical area dependence of actomyosin
contractility.
AB - During development, coordinated cell shape changes alter tissue shape. In the
Drosophila ventral furrow and other epithelia, apical constriction of hundreds of
epithelial cells folds the tissue. Genes in the Galpha12/13 pathway coordinate
collective apical constriction, but the mechanism of coordination is poorly
understood. Coupling live-cell imaging with a computational approach to identify
contractile events, we discovered that differences in constriction behavior are
biased by initial cell shape. Disrupting Galpha12/13 exacerbates this
relationship. Larger apical area is associated with delayed initiation of
contractile pulses, lower apical E-cadherin and F-actin levels, and aberrantly
mobile Rho-kinase structures. Our results suggest that loss of Galpha12/13
disrupts apical actin cortex organization and pulse initiation in a size
dependent manner. We propose that Galpha12/13 robustly organizes the apical
cortex despite variation in apical area to ensure the timely initiation of
contractile pulses in a tissue with heterogeneity in starting cell shape.
PMID- 27489341
TI - Subnuclear positioning and interchromosomal clustering of the GAL1-10 locus are
controlled by separable, interdependent mechanisms.
AB - On activation, the GAL genes in yeast are targeted to the nuclear periphery
through interaction with the nuclear pore complex. Here we identify two cis
acting "DNA zip codes" from the GAL1-10 promoter that are necessary and
sufficient to induce repositioning to the nuclear periphery. One of these zip
codes, GRS4, is also necessary and sufficient to promote clustering of GAL1-10
alleles. GRS4, and to a lesser extent GRS5, contribute to stronger expression of
GAL1 and GAL10 by increasing the fraction of cells that respond to the inducer.
The molecular mechanism controlling targeting to the NPC is distinct from the
molecular mechanism controlling interchromosomal clustering. Targeting to the
nuclear periphery and interaction with the nuclear pore complex are prerequisites
for gene clustering. However, once formed, clustering can be maintained in the
nucleoplasm, requires distinct nuclear pore proteins, and is regulated
differently through the cell cycle. In addition, whereas targeting of genes to
the NPC is independent of transcription, interchromosomal clustering requires
transcription. These results argue that zip code-dependent gene positioning at
the nuclear periphery and interchromosomal clustering represent interdependent
phenomena with distinct molecular mechanisms.
PMID- 27489342
TI - Microtubule aging probed by microfluidics-assisted tubulin washout.
AB - Microtubules switch stochastically between phases of growth and shrinkage. The
molecular mechanism responsible for the end of a growth phase, an event called
catastrophe, is still not understood. The probability for a catastrophe to occur
increases with microtubule age, putting constraints on the possible molecular
mechanism of catastrophe induction. Here we used microfluidics-assisted fast
tubulin washout experiments to induce microtubule depolymerization in a
controlled manner at different times after the start of growth. We found that
aging can also be observed in this assay, providing valuable new constraints
against which theoretical models of catastrophe induction can be tested. We found
that the data can be quantitatively well explained by a simple kinetic threshold
model that assumes an age-dependent broadening of the protective cap at the
microtubule end as a result of an evolving tapered end structure; this leads to a
decrease of the cap density and its stability. This analysis suggests an
intuitive picture of the role of morphological changes of the protective cap for
the age dependence of microtubule stability.
PMID- 27489343
TI - RIC-3 phosphorylation enables dual regulation of excitation and inhibition of
Caenorhabditis elegans muscle.
AB - Brain function depends on a delicate balance between excitation and inhibition.
Similarly, Caenorhabditis elegans motor system function depends on a precise
balance between excitation and inhibition, as C. elegans muscles receive both
inhibitory, GABAergic and excitatory, cholinergic inputs from motor neurons. Here
we show that phosphorylation of the ER-resident chaperone of nicotinic
acetylcholine receptors, RIC-3, leads to increased muscle excitability. RIC-3
phosphorylation at Ser-164 depends on opposing functions of the phosphatase
calcineurin (TAX-6), and of the casein kinase II homologue KIN-10. Effects of
calcineurin down-regulation and of phosphorylated RIC-3 on muscle excitability
are mediated by GABAA receptor inhibition. Thus RIC-3 phosphorylation enables
effects of this chaperone on GABAA receptors in addition to nAChRs. This dual
effect provides coordinated regulation of excitation and inhibition and enables
fine-tuning of the excitation-inhibition balance. Moreover, regulation of
inhibitory GABAA signaling by calcineurin, a calcium- and calmodulin-dependent
phosphatase, enables homeostatic balancing of excitation and inhibition.
PMID- 27489344
TI - Transcriptomics and Biochemical Profiling: Current Dynamics in Elucidating the
Potential Attributes of Olive.
AB - Various transcriptome studies have remained useful in unraveling the complexity
of molecular pathways regulating the oil biochemical contents and fruit
characteristics of agronomic value in olive. Genes networks associated with plant
architect and abiotic stress tolerance have been constructed due to robust
genomic data generated by the tools of genomics. This, familiarity will
accelerate the breeding programmes in making the selection of high yielding olive
genotypes promptly and efficiently. Moreover, comparative transcriptome studies
for endogeneous enzymes at different expression sites explicate the contribution
of various pathways in phenol and lipid oxidation in olive. Recently, non
targeted metabolomics and metabolic profiling techniques have not only made the
understanding of metabolic changes easy but also elucidate biomarkers in fruits
related to agronomic parameters and abiotic stresses. However, the alteration in
the architectural build up of phenotypes auth-enticates the conservation of their
potential genetic links that will invoke interest for future olive breeding.
PMID- 27489345
TI - Structural basis of HIV inhibition by translocation-defective RT inhibitor 4'
ethynyl-2-fluoro-2'-deoxyadenosine (EFdA).
AB - 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is the most potent nucleoside analog
inhibitor of HIV reverse transcriptase (RT). It retains a 3'-OH yet acts as a
chain-terminating agent by diminishing translocation from the pretranslocation
nucleotide-binding site (N site) to the posttranslocation primer-binding site (P
site). Also, facile misincorporation of EFdA-monophosphate (MP) results in
difficult-to-extend mismatched primers. To understand the high potency and
unusual inhibition mechanism of EFdA, we solved RT crystal structures
(resolutions from 2.4 to 2.9 A) that include inhibition intermediates (i) before
inhibitor incorporation (catalytic complex, RT/DNA/EFdA-triphosphate), (ii) after
incorporation of EFdA-MP followed by dT-MP (RT/DNAEFdA-MP(P)* dT-MP(N) ), or
(iii) after incorporation of two EFdA-MPs (RT/DNAEFdA-MP(P)* EFdA-MP(N) ); (iv)
the latter was also solved with EFdA-MP mismatched at the N site (RT/DNAEFdA
MP(P)* EFdA-MP(*N) ). We report that the inhibition mechanism and potency of EFdA
stem from interactions of its 4'-ethynyl at a previously unexploited conserved
hydrophobic pocket in the polymerase active site. The high resolution of the
catalytic complex structure revealed a network of ordered water molecules at the
polymerase active site that stabilize enzyme interactions with nucleotide and DNA
substrates. Finally, decreased translocation results from favorable interactions
of primer-terminating EFdA-MP at the pretranslocation site and unfavorable
posttranslocation interactions that lead to observed localized primer
distortions.
PMID- 27489346
TI - Pacemaker-neuron-dependent disturbance of the molecular clockwork by a Drosophila
CLOCK mutant homologous to the mouse Clock mutation.
AB - Circadian clocks are composed of transcriptional/translational feedback loops
(TTFLs) at the cellular level. In Drosophila TTFLs, the transcription factor
dCLOCK (dCLK)/CYCLE (CYC) activates clock target gene expression, which is
repressed by the physical interaction with PERIOD (PER). Here, we show that amino
acids (AA) 657-707 of dCLK, a region that is homologous to the mouse Clock exon
19-encoded region, is crucial for PER binding and E-box-dependent transactivation
in S2 cells. Consistently, in transgenic flies expressing dCLK with an AA657-707
deletion in the Clock (Clk(out)) genetic background (p{dClk-Delta};Clk(out)),
oscillation of core clock genes' mRNAs displayed diminished amplitude compared
with control flies, and the highly abundant dCLKDelta657-707 showed significantly
decreased binding to PER. Behaviorally, the p{dClk-Delta};Clk(out) flies
exhibited arrhythmic locomotor behavior in the photic entrainment condition but
showed anticipatory activities of temperature transition and improved free
running rhythms in the temperature entrainment condition. Surprisingly, p{dClk
Delta};Clk(out) flies showed pacemaker-neuron-dependent alterations in molecular
rhythms; the abundance of dCLK target clock proteins was reduced in ventral
lateral neurons (LNvs) but not in dorsal neurons (DNs) in both entrainment
conditions. In p{dClk-Delta};Clk(out) flies, however, strong but delayed
molecular oscillations in temperature cycle-sensitive pacemaker neurons, such as
DN1s and DN2s, were correlated with delayed anticipatory activities of
temperature transition. Taken together, our study reveals that the LNv molecular
clockwork is more sensitive than the clockwork of DNs to dysregulation of dCLK by
AA657-707 deletion. Therefore, we propose that the dCLK/CYC-controlled TTFL
operates differently in subsets of pacemaker neurons, which may contribute to
their specific functions.
PMID- 27489347
TI - microRNA-309 targets the Homeobox gene SIX4 and controls ovarian development in
the mosquito Aedes aegypti.
AB - Obligatory blood-triggered reproductive strategy is an evolutionary adaptation of
mosquitoes for rapid egg development. It contributes to the vectorial capacity of
these insects. Therefore, understanding the molecular mechanisms underlying
reproductive processes is of particular importance. Here, we report that microRNA
309 (miR-309) plays a critical role in mosquito reproduction. A spatiotemporal
expression profile of miR-309 displayed its blood feeding-dependent onset and
ovary-specific manifestation in female Aedes aegypti mosquitoes. Antagomir
silencing of miR-309 impaired ovarian development and resulted in nonsynchronized
follicle growth. Furthermore, the genetic disruption of miR-309 by CRISPR/Cas9
system led to the developmental failure of primary follicle formation.
Examination of genomic responses to miR-309 depletion revealed that several
pathways associated with ovarian development are down-regulated. Comparative
analysis of genes obtained from the high-throughput RNA sequencing of ovarian
tissue from the miR-309 antagomir-silenced mosquitoes with those from the in
silico computation target prediction identified that the gene-encoding SIX
homeobox 4 protein (SIX4) is a putative target of miR-309. Reporter assay and RNA
immunoprecipitation confirmed that SIX4 is a direct target of miR-309. RNA
interference of SIX4 was able to rescue phenotypic manifestations caused by miR
309 depletion. Thus, miR-309 plays a critical role in mosquito reproduction by
targeting SIX4 in the ovary and serves as a regulatory switch permitting a stage
specific degradation of the ovarian SIX4 mRNA. In turn, this microRNA (miRNA)
targeted degradation is required for appropriate initiation of a blood feeding
triggered phase of ovarian development, highlighting involvement of this miRNA in
mosquito reproduction.
PMID- 27489349
TI - Hypoxia-NOTCH1-SOX2 signaling is important for maintaining cancer stem cells in
ovarian cancer.
AB - Hypoxia and NOTCH signaling have been reported to be associated with the self
renewal and drug resistance of cancer stem cells (CSCs). However, the molecular
mechanisms by which hypoxia and NOTCH signaling stimulate the self-renewal and
drug resistance of ovarian CSCs are poorly understood. In the present study, we
identified SOX2 as a key transcription factor for CSC-like characteristics in the
downstream of hypoxia-induced NOTCH signaling in epithelial ovarian cancer cells.
Hypoxic treatment or overexpression of intracellular domain of NOTCH1 (NICD1) in
ovarian cancer cells increased sphere formation, drug resistance, and expression
of CSC-associated genes such as SOX2, ALDH, and ABC transporters. Hypoxic
treatment increased the expression of NICD1, and hypoxic treatment or NICD1
overexpression increased SOX2 promoter activity, which was inhibited by deletion
of HIF-1 or CSL binding sites. Furthermore, DAPT treatment decreased the effect
of hypoxic treatment, and SOX2 knockdown decreased the effect of hypoxic
treatment and NICD overexpression on sphere formation and drug resistance in
established ovarian cancer cell lines and primary ovarian cancer cells. These
results suggest that hypoxia-NOTCH1-SOX2 signaling axis is important for
activation of ovarian CSCs, which may provide a novel opportunity for developing
therapeutics to eradicate CSCs in ovarian cancer patients.
PMID- 27489348
TI - Structure of fully protonated proteins by proton-detected magic-angle spinning
NMR.
AB - Protein structure determination by proton-detected magic-angle spinning (MAS) NMR
has focused on highly deuterated samples, in which only a small number of protons
are introduced and observation of signals from side chains is extremely limited.
Here, we show in two fully protonated proteins that, at 100-kHz MAS and above,
spectral resolution is high enough to detect resolved correlations from amide and
side-chain protons of all residue types, and to reliably measure a dense network
of (1)H-(1)H proximities that define a protein structure. The high data quality
allowed the correct identification of internuclear distance restraints encoded in
3D spectra with automated data analysis, resulting in accurate, unbiased, and
fast structure determination. Additionally, we find that narrower proton
resonance lines, longer coherence lifetimes, and improved magnetization transfer
offset the reduced sample size at 100-kHz spinning and above. Less than 2 weeks
of experiment time and a single 0.5-mg sample was sufficient for the acquisition
of all data necessary for backbone and side-chain resonance assignment and
unsupervised structure determination. We expect the technique to pave the way for
atomic-resolution structure analysis applicable to a wide range of proteins.
PMID- 27489350
TI - Phosphatidyl inositol-3 kinase (PIK3CA) E545K mutation confers cisplatin
resistance and a migratory phenotype in cervical cancer cells.
AB - The phosphatidylinositol-3 kinase (PI3K)/Akt/mTOR signaling pathway is activated
in many human cancers. Previously, we reported that patients with early stage
cervical cancer whose tumours harbour PIK3CA exon 9 or 20 mutations have worse
overall survival in response to treatment with radiation and cisplatin than
patients with wild-type PIK3CA. The purpose of this study was to determine
whether PIK3CA-E545K mutation renders cervical cancer cells more resistant to
cisplatin and/or radiation, and whether PI3K inhibition reverses the phenotype.
We found that CaSki cells that are heterozygous for the PIK3CA-E545K mutation are
more resistant to cisplatin or cisplatin plus radiation than either HeLa or SiHa
cells that express only wild-type PIK3CA. Similarly, HeLa cells engineered to
stably express PIK3CA-E545K were more resistant to cisplatin or cisplatin plus
radiation than cells expressing only wild-type PIK3CA or with PIK3CA depleted.
Cells expressing the PIK3CA-E545K mutation also had constitutive PI3K pathway
activation and increased cellular migration and each of these phenotypes was
reversed by treatment with the PI3K inhibitor GDC-0941/Pictilisib. Our results
suggests that cervical cancer patients whose tumours are positive for the PIK3CA
E545K mutation may benefit from PI3K inhibitor therapy in concert with standard
cisplatin and radiation therapy.
PMID- 27489351
TI - Constitutive gp130 activation rapidly accelerates the transformation of human
hepatocytes via an impaired oxidative stress response.
AB - Pro-inflammatory signaling pathways, especially interleukin 6 (IL-6), and
reactive oxygen species (ROS) promote carcinogenesis in the liver. In order to
elucidate the underlying oncogenic mechanism, we activated the IL-6 signal
transducer glycoprotein 130 (gp130) via stable expression of a constitutively
active gp130 construct (L-gp130) in untransformed telomerase-immortalized human
fetal hepatocytes (FH-hTERT). As known from hepatocellular adenomas, forced gp130
activation alone was not sufficient to induce malignant transformation. However,
additional challenge of FH-hTERT L-gp130 clones with oxidative stress resulted in
2- to 3-fold higher ROS levels and up to 6-fold more DNA-double strand breaks
(DSB). Despite increased DNA damage, ROS-challenged FH-hTERT L-gp130 clones
displayed an enhanced proliferation and rapidly developed colony growth
capabilities in soft agar. As driving gp130-mediated oncogenic mechanism, we
detected a decreased expression of antioxidant genes, in particular glutathione
peroxidase 3 and apolipoprotein E, and an absence of P21 upregulation following
ROS-conferred induction of DSB. In summary, an impaired oxidative stress response
in hepatocytes with gp130 gain-of-function mutations, as detected in dysplastic
intrahepatic nodules and hepatocellular adenomas, is one of the central oncogenic
mechanisms in chronic liver inflammation.
PMID- 27489352
TI - S18 family of mitochondrial ribosomal proteins: evolutionary history and Gly132
polymorphism in colon carcinoma.
AB - S18 family of mitochondrial ribosomal proteins (MRPS18, S18) consists of three
members, S18-1 to -3. Earlier, we found that overexpression of S18-2 protein
resulted in immortalization and eventual transformation of primary rat
fibroblasts. The S18-1 and -3 have not exhibited such abilities. To understand
the differences in protein properties, the evolutionary history of S18 family was
analyzed. The S18-3, followed by S18-1 and S18-2 emerged as a result of ancient
gene duplication in the root of eukaryotic species tree, followed by two metazoan
specific gene duplications. However, the most conserved metazoan S18 homolog is
the S18-1; it shares the most sequence similarity with S18 proteins of bacteria
and of other eukaryotic clades. Evolutionarily conserved residues of S18 proteins
were analyzed in various cancers. S18-2 is mutated at a higher rate, compared
with S18-1 and -3 proteins. Moreover, the evolutionarily conserved residue,
Gly132 of S18-2, shows genetic polymorphism in colon adenocarcinomas that was
confirmed by direct DNA sequencing.Concluding, S18 family represents the yet
unexplored important mitochondrial ribosomal proteins.
PMID- 27489353
TI - HPV16 E6-E7 induces cancer stem-like cells phenotypes in esophageal squamous cell
carcinoma through the activation of PI3K/Akt signaling pathway in vitro and in
vivo.
AB - High-risk human papillomavirus (HPV), especially HPV16, correlates with
cancerogenesis of human esophageal squamous cell carcinoma (ESCC) and we have
reported that HPV16 related with a poor prognosis of ESCC patients in China. We
aim to investigate the potential role and mechanism of HPV16 in ESCC development
and progress. Our following researches demonstrated that ESCC cells which were
stably transfected by HPV16 E6-E7 lentiviral vector showed a remarkable cancer
stem-like cells (CSCs) phenotype, such as: migration, invasion, spherogenesis,
high expression of CSCs marker in ESCC---p75NTR, chemoresistance,
radioresistance, anti-apoptosis ability in vitro and cancerogenesis in vivo.
HPV16 E6-E7 induced PI3K/Akt signaling pathway activation and this affect could
be effectively inhibited by LY294002, a specific PI3K inhibitor. It was also
indicated that the inhibition of PI3K/Akt signaling pathway by PI3K and Akt siRNA
reverse the effect which induced by HPV16 E6-E7 in ESCC cells. Taken together,
the present study demonstrates that HPV16 E6-E7 promotes CSCs phenotype in ESCC
cells through the activation of PI3K/Akt signaling pathway. Targeting the
PI3K/Akt signaling pathway in HPV16 positive tissues is an available therapeutic
for ESCC patients.
PMID- 27489354
TI - Association of the GLB1 rs4678680 genetic variant with risk of HBV-related
hepatocellular carcinoma.
AB - Accumulated evidences demonstrated that GLB1 is involved in cell senescence and
cancer development. The GLB1 rs4678680 single nucleotide polymorphism (SNP) has
been identified as a hepatocellular carcinoma (HCC) susceptibility polymorphism
by a genome-wide association study in Korean population previously. However,
little or nothing was known about its involvement and functional significance in
hepatitis B viruses (HBV)-related HCC in Chinese. Therefore, we investigated the
association between the GLB1 rs4678680 SNP and HBV-related HCC risk as well as
its biological function in vivo. Genotypes were determined in two independent
case-control sets from two medical centers of China. Odds ratios (ORs) and 95%
confidence intervals (CIs) were estimated by logistic regression. The potential
regulation role the rs4678680 genetic variant on GLB1 expression was examined
with HCC and normal liver tissues. We found that The rs4678680 G allele was
showed to be risk allele; individuals with the TG genotype had an OR of 1.51 (95%
CI = 1.10-2.07, P = 0.010, Shandong set) or 1.49 (95% CI = 1.11-1.99, P = 0.008,
Jiangsu set) for developing HBV-related HCC, respectively, compared with
individuals with the TT genotype. This association was more pronounced in males,
individuals aged older than 57 years and drinkers (all P < 0.05). In the genotype
phenotype correlation analyses of fifty-six human liver tissue samples, rs4678680
TG or GG was associated with a statistically significant increase of GLB1 mRNA
expression (P < 0.05). Our data indicated that the GLB1 rs4678680 SNP contributes
to susceptibility to develop HBV-related HCC, highlighting the involvement of
GLB1 and cell senescence in etiology of HCC.
PMID- 27489355
TI - The prognostic value of CSCs biomarker CD133 in NSCLC: a meta-analysis.
AB - The prognostic value of cancer stem cells (CSCs) marker CD133 in non-small-cell
lung cancer (NSCLC) remains controversial. We performed this meta-analysis of 32
eligible studies to clarify the prognostic value of CD133 and provide evidence
for CSCs hypothesis. We calculated pooled hazard ratio (HR) for survival outcomes
and pooled odds ratio (OR) for clinical parameters associated with CD133 in total
3595 NSCLC patients by STATA. Our results showed that NSCLC patients with higher
CD133 expression had shorter overall survival time only in Asian patients (HR =
3.80, 95% CI: 3.12-4.04, p < 0.001; I2 = 32%) but not in Caucasian patients (HR =
1.15, 95% CI: 0.88-1.52, p = 0.307; I2 = 0%), suggesting that differential
prognostic value of CD133 in distinct ethnic group. We speculated that the
intrinsic EGFR gene status of CSCs might be responsible for this racial
difference. Additionally, we found that higher expression of CD133 was associated
with poor differentiation (OR = 2.03, 95% CI: 1.32-3.14, p = 0.001) and lymph
node metastasis (OR = 2.39, 95% CI: 1.62-3.52, p < 0.001) but there was no
significant difference of CD133 expression between adenocarcinoma and squamous
carcinoma (OR = 1.13, 95% CI: 0.93-1.38, p = 0.3) in NSCLC patients. These
results may provide a new therapeutic perspective on the treatment of NSCLC
patients according to the expression of CD133 in distinct ethnic group.
PMID- 27489356
TI - A scoring system basing pathological parameters to predict regional lymph node
metastasis after preoperative chemoradiotherapy for locally advanced rectal
cancer: implication for local excision.
AB - Local excision is an alternative to radical surgery that is indicated in patients
with locally advanced rectal cancer (LARC) who have a good response to
chemoradiotherapy (CRT). Regional lymph node status is a major uncertainty during
local excision of LARC following CRT. We retrospectively reviewed
clinicopathologic variables for 244 patients with LARC who were treated at our
institute between December 2000 and December 2013 in order to identify
independent predictors of regional lymph node metastasis. Multivariate analysis
of the training sample demonstrated that histopathologic type, tumor size, and
the presence of lymphovascular invasion were significant predictors of regional
nodal metastasis. These variables were then incorporated into a scoring system in
which the total scores were calculated based on the points assigned for each
parameter. The area under the curve in the receiver operating characteristic
analysis was 0.750, and the cutoff value for the total score to predict regional
nodal metastasis was 7.5. The sensitivity of our system was 73.2% and the
specificity was 69.4%. The sensitivity was 77.8% and the specificity was 51.2%
when the scoring system was applied to the testing sample. Using this system, we
could accurately predict regional nodal metastases in LARC patients following
CRT, which may be useful for stratifying patients in clinical trials and
selecting potential candidates for organ-sparing surgery following CRT for LARC.
PMID- 27489357
TI - Increased frequency of circulating Th22 cells in patients with B-cell non
Hodgkin's lymphoma.
AB - T helper (Th) 22 cells play important roles in the pathogenesis of autoimmune and
inflammatory diseases, and their function in tumors remains uncertain. In the
current study, we investigated the alternations and clinical significance of
circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma (B-NHL). We
found that the frequency of Th22 cells was significantly elevated in peripheral
blood of newly-diagnosed B-NHL patients, and returned to normal level after
chemotherapy. In consistent with increased Th22 frequency, plasma IL-22 and IL-6
levels in B-NHL patients were remarkably increased. Moreover, the increased Th22
frequency was associated with the older age (> 60 yr) and a poorer response to
therapy in B-NHL patients. In addition, there existed a statistically positive
correlation between circulating Th22 and Th17 frequencies in B-NHL patients. Our
data demonstrated that circulating Th22 frequency was associated with the
clinical outcome and prognosis of B-NHL patients, indicating that Th22 immune
response might play an important role in the development and progression of B
NHL.
PMID- 27489358
TI - Notch1 directly induced CD133 expression in human diffuse type gastric cancers.
AB - CD133 is considered as a stem-like cell marker in some cancers including gastric
cancers, and Notch1 signaling is known to play an important role in the
maintenance and differentiation of stem-like cells. We aimed to investigate
whether Notch1 signaling contributes to the carcinogenesis of gastric cancers and
CD133 induction. CD133 expression was detected in 51.4% of diffuse type gastric
cancers while it was not detected in intestinal type gastric cancers. Similarly,
only poorly-differentiated gastric cancer cell lines expressed CD133 and
activated-Notch1. Inhibiting Notch1 signaling resulted in decreased CD133
expression, side population cells, cell proliferation and anchorage independent
cell growth. Chromatin immunoprecipitation suggested that this Notch1 dependent
regulation of CD133 was caused by direct binding of activated-Notch1 to the RBP
Jkappa binding site in the 5' promoter region of CD133 gene. In addition,
knocking down RBP-Jkappa reduced CD133 induction in activated-Notch1 transfected
cells. These findings suggested that Notch1 signaling plays an important role in
the maintenance of the cancer stem-like phenotype in diffuse type gastric cancer
through an RBP-Jkappa dependent pathway and that inhibiting Notch1 signaling
could be an effective therapy against CD133 positive diffuse type gastric
cancers.
PMID- 27489359
TI - Urban-rural disparity of overweight/obesity distribution and its potential trend
with breast cancer among Chinese women.
AB - OBJECTIVE: To evaluate the urban-rural disparity of overweight/obesity and
explore its potential trend with breast cancer among Chinese women. RESULTS: The
prevalence of overweight/obesity for Chinese rural women (35.2%, 29.2% for
overweight and 6.0% for obesity) was significantly higher than that for Chinese
urban women (33.4%, 27.7% for overweight and 5.7% for obesity) (P < 0.001). For
either rural or urban women, the prevalence of overweight/obesity was highest in
north region, followed by east region for rural women and north-east region for
urban women. For rural women, higher prevalence of overweight/obesity was
significantly positively associated with elder age, Han nationality, low level of
education, no occupation, high family income, less number of family residents,
insurance, and elder age at marriage. Similar positive associations were also
found for urban women, except negative associations for high family income, less
number of family residents, and elder age at marriage. A non-significant positive
trend between overweight/obesity and breast cancer was found for rural women
[odds ratio (OR): 1.06; 95% confidence interval (CI): 0.87-1.29], but a
significant positive trend for urban women (OR: 1.55; 95% CI: 1.19-2.02).
MATERIALS AND METHODS: A total of 1 210 762 participants were recruited from the
Chinese National Breast Cancer Screening Program. Overweight and obesity were
defined as body mass index (BMI) ranged 24.0-27.9 kg/m2 and BMI >= 28.0kg/m2,
respectively. CONCLUSIONS: There was an obvious urban-rural disparity of
overweight/obesity distribution among Chinese women, which could also lead to an
obvious disparity of breast cancer distribution.
PMID- 27489360
TI - Amplification of TLK2 Induces Genomic Instability via Impairing the G2-M
Checkpoint.
AB - : Managing aggressive breast cancers with enhanced chromosomal instability (CIN)
is a significant challenge in clinics. Previously, we described that a cell cycle
associated kinase called Tousled-like kinase 2 (TLK2) is frequently deregulated
by genomic amplifications in aggressive estrogen receptor-positive (ER+) breast
cancers. In this study, it was discovered that TLK2 amplification and
overexpression mechanistically impair Chk1/2-induced DNA damage checkpoint
signaling, leading to a G2-M checkpoint defect, delayed DNA repair process, and
increased CIN. In addition, TLK2 overexpression modestly sensitizes breast cancer
cells to DNA-damaging agents, such as irradiation or doxorubicin. To our
knowledge, this is the first report linking TLK2 function to CIN, in contrast to
the function of its paralog TLK1 as a guardian of genome stability. This finding
yields new insight into the deregulated DNA damage pathway and increased genomic
instability in aggressive ER+ breast cancers. IMPLICATIONS: Targeting TLK2
presents an attractive therapeutic strategy for the TLK2-amplified breast cancers
that possess enhanced genomic instability and aggressiveness. Mol Cancer Res;
14(10); 920-7. (c)2016 AACR.
PMID- 27489361
TI - Systemic Ablation of MMP-9 Triggers Invasive Growth and Metastasis of Pancreatic
Cancer via Deregulation of IL6 Expression in the Bone Marrow.
AB - : Matrix metalloproteinase 9 (MMP-9/Gelatinase B) is overexpressed in pancreatic
ductal adenocarcinoma (PDAC) and plays a central role in tumor cell invasion and
metastasis. Here we complemented mechanistic insights in the cancer biology of
MMP-9 and investigated the effects of specific long-term loss-of-function, by
genetic ablation, of MMP-9 on PDAC initiation and progression in the well
established KPC mouse model of spontaneous PDAC. Tumor growth and progression
were analyzed by histopathology and IHC. Invasive growth of PDAC cells was
analyzed by both in vitro (proliferation, survival, migration, invasion assays)
and in vivo (experimental metastasis assays) methods. Retroviral shRNAi was used
to knockdown target genes (MMP-9, IL6R). Gene expression was analyzed by qRT-PCR,
immunoblot, ELISA, in situ hybridization, and zymography. PDAC tumors from MMP-9
deficient mice were dramatically larger, more invasive, and contained more
stroma. Yet, ablation of MMP-9 in PDAC cells did not directly promote invasive
growth. Interestingly, systemic ablation of MMP-9 led to increased IL6 levels
resulting from abrogation of MMP-9-dependent SCF signaling in the bone marrow.
IL6 levels in MMP-9-/- mice were sufficient to induce invasive growth and STAT3
activation in PDAC cells via IL6 receptor (IL6R). Interference with IL6R blocked
the increased invasion and metastasis of PDAC cells in MMP-9-deficient hosts. In
conclusion, ablation of systemic MMP-9 initiated fatal communication between
maintenance of physiological functions of MMP-9 in the bone marrow and invasive
growth of PDAC via the IL6/IL6R/STAT3 axis. IMPLICATIONS: Thus, the beneficial
effects of host MMP-9 on PDAC are an important caveat for the use of systemic MMP
9 inhibitors in cancer. Mol Cancer Res; 14(11); 1147-58. (c)2016 AACR.
PMID- 27489362
TI - Mechanical effort predicts the selection of ankle over hip strategies in
nonstepping postural responses.
AB - Experimental studies have shown that a continuum of ankle and hip strategies is
used to restore posture following an external perturbation. Postural responses
can be modeled by feedback control with feedback gains that optimize a specific
objective. On the one hand, feedback gains that minimize effort have been used to
predict muscle activity during perturbed standing. On the other hand, hip and
ankle strategies have been predicted by minimizing postural instability and
deviation from upright posture. It remains unclear, however, whether and how
effort minimization influences the selection of a specific postural response. We
hypothesize that the relative importance of minimizing mechanical work vs.
postural instability influences the strategy used to restore upright posture.
This hypothesis was investigated based on experiments and predictive simulations
of the postural response following a backward support surface translation. Peak
hip flexion angle was significantly correlated with three experimentally
determined measures of effort, i.e., mechanical work, mean muscle activity and
metabolic energy. Furthermore, a continuum of ankle and hip strategies was
predicted in simulation when changing the relative importance of minimizing
mechanical work and postural instability, with increased weighting of mechanical
work resulting in an ankle strategy. In conclusion, the combination of
experimental measurements and predictive simulations of the postural response to
a backward support surface translation showed that the trade-off between effort
and postural instability minimization can explain the selection of a specific
postural response in the continuum of potential ankle and hip strategies.
PMID- 27489363
TI - Sour taste increases swallowing and prolongs hemodynamic responses in the
cortical swallowing network.
AB - Sour stimuli have been shown to upregulate swallowing in patients and in healthy
volunteers. However, such changes may be dependent on taste-induced increases in
salivary flow. Other mechanisms include genetic taster status (Bartoshuk LM,
Duffy VB, Green BG, Hoffman HJ, Ko CW, Lucchina LA, Weiffenbach JM. Physiol Behav
82: 109-114, 2004) and differences between sour and other tastes. We investigated
the effects of taste on swallowing frequency and cortical activation in the
swallowing network and whether taster status affected responses. Three-milliliter
boluses of sour, sour with slow infusion, sweet, water, and water with infusion
were compared on swallowing frequency and hemodynamic responses. The sour
conditions increased swallowing frequency, whereas sweet and water did not.
Changes in cortical oxygenated hemoglobin (hemodynamic responses) measured by
functional near-infrared spectroscopy were averaged over 30 trials for each
condition per participant in the right and left motor cortex, S1 and
supplementary motor area for 30 s following bolus onset. Motion artifact in the
hemodynamic response occurred 0-2 s after bolus onset, when the majority of
swallows occurred. The peak hemodynamic response 2-7 s after bolus onset did not
differ by taste, hemisphere, or cortical location. The mean hemodynamic response
17-22 s after bolus onset was highest in the motor regions of both hemispheres,
and greater in the sour and infusion condition than in the water condition.
Genetic taster status did not alter changes in swallowing frequency or
hemodynamic response. As sour taste significantly increased swallowing and
cortical activation equally with and without slow infusion, increases in the
cortical swallowing were due to sour taste.
PMID- 27489364
TI - Responses of non-eye-movement central vestibular neurons to sinusoidal yaw
rotation in compensated macaques after unilateral semicircular canal plugging.
AB - After vestibular labyrinth injury, behavioral measures of vestibular performance
recover to variable degrees (vestibular compensation). Central neuronal responses
after unilateral labyrinthectomy (UL), which eliminates both afferent resting
activity and sensitivity to movement, have been well-studied. However, unilateral
semicircular canal plugging (UCP), which attenuates angular-velocity detection
while leaving afferent resting activity intact, has not been extensively studied.
The current study reports response properties of yaw-sensitive non-eye-movement
rhesus macaque vestibular neurons after compensation from UCP. The responses at a
series of frequencies (0.1-2 Hz) and peak velocities (15-210 degrees /s) were
compared between neurons recorded before and at least 6 wk after UCP. The gain
(sp/s/ degrees /s) of central type I neurons (responding to ipsilateral yaw
rotation) on the side of UCP was reduced relative to normal controls at 0.5 Hz,
+/-60 degrees /s [0.48 +/- 0.30 (SD) normal, 0.32 +/- 0.15 ipsilesion; 0.44 +/-
0.2 contralesion]. Type II neurons (responding to contralateral yaw rotation)
after UCP have reduced gain (0.40 +/- 0.27 normal, 0.35 +/- 0.25 ipsilesion; 0.25
+/- 0.18 contralesion). The difference between responses after UCP and after UL
is primarily the distribution of type I and type II neurons in the vestibular
nuclei (type I neurons comprise 66% in vestibular nuclei normally; 51% ipsilesion
UCP; 59% contralesion UCP; 38% ipsilesion UL; 65% contralesion UL) and the
magnitude of the responses of type II neurons ipsilateral to the lesion. These
differences suggest that the need to compensate for unilateral loss of resting
vestibular nerve activity after UL necessitates a different strategy for recovery
of dynamic vestibular responses compared to after UCP.
PMID- 27489365
TI - Motor outcomes of feedback delays and implicit/explicit strategy use:
experimental considerations and clinical implications.
AB - Sensorimotor adaptation requires integration of internal models of motor control
with feedback from the external environment. As highlighted by Brudner, Kethidi,
Graeupner, Ivry, and Taylor (J Neurophysiol 115: 1499-1511, 2016), feedback
characteristics, error or outcome based, as well as temporal constraints can
impact motor learning and adaptation strategies. These findings provide novel
insight into the underlying components of motor control, which can be applied to
future clinical and experimental research on motor processes.
PMID- 27489366
TI - Losing touch: age-related changes in plantar skin sensitivity, lower limb
cutaneous reflex strength, and postural stability in older adults.
AB - Age-related changes in the density, morphology, and physiology of plantar
cutaneous receptors negatively impact the quality and quantity of balance
relevant information arising from the foot soles. Plantar perceptual sensitivity
declines with age and may predict postural instability; however, alteration in
lower limb cutaneous reflex strength may also explain greater instability in
older adults and has yet to be investigated. We replicated the age-related
decline in sensitivity by assessing monofilament and vibrotactile (30 and 250 Hz)
detection thresholds near the first metatarsal head bilaterally in healthy young
and older adults. We additionally applied continuous 30- and 250-Hz vibration to
drive mechanically evoked reflex responses in the tibialis anterior muscle,
measured via surface electromyography. To investigate potential relationships
between plantar sensitivity, cutaneous reflex strength, and postural stability,
we performed posturography in subjects during quiet standing without vision.
Anteroposterior and mediolateral postural stability decreased with age, and
increases in postural sway amplitude and frequency were significantly correlated
with increases in plantar detection thresholds. With 30-Hz vibration, cutaneous
reflexes were observed in 95% of young adults but in only 53% of older adults,
and reflex gain, coherence, and cumulant density at 30 Hz were lower in older
adults. Reflexes were not observed with 250-Hz vibration, suggesting this high
frequency cutaneous input is filtered out by motoneurons innervating tibialis
anterior. Our findings have important implications for assessing the risk of
balance impairment in older adults.
PMID- 27489367
TI - Postsynaptic nicotinic acetylcholine receptors facilitate excitation of
developing CA1 pyramidal neurons.
AB - The hippocampus plays a key role in learning and memory. The normal development
and mature function of hippocampal networks supporting these cognitive functions
depends on afferent cholinergic neurotransmission mediated by nicotinic
acetylcholine receptors. Whereas it is well-established that nicotinic receptors
are present on GABAergic interneurons and on glutamatergic presynaptic terminals
within the hippocampus, the ability of these receptors to mediate postsynaptic
signaling in pyramidal neurons is not well understood. We use whole cell
electrophysiology to show that heteromeric nicotinic receptors mediate direct
inward currents, depolarization from rest and enhanced excitability in
hippocampus CA1 pyramidal neurons of male mice. Measurements made throughout
postnatal development provide a thorough developmental profile for these
heteromeric nicotinic responses, which are greatest during the first 2 wk of
postnatal life and decrease to low adult levels shortly thereafter.
Pharmacological experiments show that responses are blocked by a competitive
antagonist of alpha4beta2* nicotinic receptors and augmented by a positive
allosteric modulator of alpha5 subunit-containing receptors, which is consistent
with expression studies suggesting the presence of alpha4beta2 and
alpha4beta2alpha5 nicotinic receptors within the developing CA1 pyramidal cell
layer. These findings demonstrate that functional heteromeric nicotinic receptors
are present on CA1 pyramidal neurons during a period of major hippocampal
development, placing these receptors in a prime position to play an important
role in the establishment of hippocampal cognitive networks.
PMID- 27489368
TI - Cerebellar tDCS dissociates the timing of perceptual decisions from perceptual
change in speech.
AB - Neuroimaging studies suggest that the cerebellum might play a role in both speech
perception and speech perceptual learning. However, it remains unclear what this
role is: does the cerebellum help shape the perceptual decision, or does it
contribute to the timing of perceptual decisions? To test this, we used
transcranial direct current stimulation (tDCS) in combination with a speech
perception task. Participants experienced a series of speech perceptual tests
designed to measure and then manipulate (via training) their perception of a
phonetic contrast. One group received cerebellar tDCS during speech perceptual
learning, and a different group received sham tDCS during the same task. Both
groups showed similar learning-related changes in speech perception that
transferred to a different phonetic contrast. For both trained and untrained
speech perceptual decisions, cerebellar tDCS significantly increased the time it
took participants to indicate their decisions with a keyboard press. By analyzing
perceptual responses made by both hands, we present evidence that cerebellar tDCS
disrupted the timing of perceptual decisions, while leaving the eventual decision
unaltered. In support of this conclusion, we use the drift diffusion model to
decompose the data into processes that determine the outcome of perceptual
decision-making and those that do not. The modeling suggests that cerebellar tDCS
disrupted processes unrelated to decision-making. Taken together, the empirical
data and modeling demonstrate that right cerebellar tDCS dissociates the timing
of perceptual decisions from perceptual change. The results provide initial
evidence in healthy humans that the cerebellum critically contributes to speech
timing in the perceptual domain.
PMID- 27489369
TI - Spatial spread of local field potential is band-pass in the primary visual
cortex.
AB - Local field potential (LFP) is a valuable tool in understanding brain function
and in brain machine-interfacing applications. However, there is no consensus on
the spatial extent of the cortex that contributes to the LFP (its "spatial
spread"), with different studies reporting values between a few hundred
micrometers and several millimeters. Furthermore, the dependency of the spatial
spread on frequency, which could reflect properties of the network architecture
and extracellular medium, is not well studied, with theory and models predicting
either "all-pass" (frequency-independent) or "low-pass" behavior. Surprisingly,
we found the LFP spread to be "band-pass" in the primate primary visual cortex,
with the greatest spread in the high-gamma range (60-150 Hz). This was
accompanied by an increase in phase coherency across neighboring sites in the
same frequency range, consistent with the findings of a recent model that
reconciles previous studies by suggesting that spatial spread depends on neuronal
correlations.
PMID- 27489370
TI - High-fidelity optical excitation of cortico-cortical projections at physiological
frequencies.
AB - Optogenetic activation of axons is a powerful approach for determining the
synaptic properties and impact of long-range projections both in vivo and in
vitro. However, because of the difficulty of measuring activity in axons, our
knowledge of the reliability of optogenetic axonal stimulation has relied on data
from somatic recordings. Yet, there are many reasons why activation of axons may
not be comparable to cell bodies. Thus we have developed an approach to more
directly assess the fidelity of optogenetic activation of axonal projections. We
expressed opsins (ChR2, Chronos, or oChIEF) in the mouse primary visual cortex
(V1) and recorded extracellular, pharmacologically isolated presynaptic action
potentials in response to axonal activation in the higher visual areas.
Repetitive stimulation of axons with ChR2 resulted in a 70% reduction in the
fiber volley amplitude and a 60% increase in the latency at all frequencies
tested (10-40 Hz). Thus ChR2 cannot reliably recruit axons during repetitive
stimulation, even at frequencies that are reliable for somatic stimulation,
likely due to pronounced channel inactivation at the high light powers required
to evoke action potentials. By comparison, oChIEF and Chronos evoked
photocurrents that inactivated minimally and could produce reliable axon
stimulation at frequencies up to 60 Hz. Our approach provides a more direct and
accurate evaluation of the efficacy of new optogenetic tools and has identified
Chronos and oChIEF as viable tools to interrogate the synaptic and circuit
function of long-range projections.
PMID- 27489371
TI - Effect of phenytoin on sodium conductances in rat hippocampal CA1 pyramidal
neurons.
AB - The antiepileptic drug phenytoin (PHT) is thought to reduce the excitability of
neural tissue by stabilizing sodium channels (NaV) in inactivated states. It has
been suggested the fast-inactivated state (IF) is the main target, although slow
inactivation (IS) has also been implicated. Other studies on local anesthetics
with similar effects on sodium channels have implicated the NaV voltage sensor
interactions. In this study, we reexamined the effect of PHT in both equilibrium
and dynamic transitions between fast and slower forms of inactivation in rat
hippocampal CA1 pyramidal neurons. The effects of PHT were observed on fast and
slow inactivation processes, as well as on another identified "intermediate"
inactivation process. The effect of enzymatic removal of IF was also studied, as
well as effects on the residual persistent sodium current (INaP). A computational
model based on a gating charge interaction was derived that reproduced a range of
PHT effects on NaV equilibrium and state transitions. No effect of PHT on IF was
observed; rather, PHT appeared to facilitate the occupancy of other closed
states, either through enhancement of slow inactivation or through formation of
analogous drug-bound states. The overall significance of these observations is
that our data are inconsistent with the commonly held view that the archetypal
NaV channel inhibitor PHT stabilizes fast inactivation states, and we demonstrate
that conventional slow activation "IS" and the more recently identified
intermediate-duration inactivation process "II" are the primary functional
targets of PHT. In addition, we show that the traditional explanatory frameworks
based on the "modulated receptor hypothesis" can be substituted by simple,
physiologically plausible interactions with voltage sensors. Additionally, INaP
was not preferentially inhibited compared with peak INa at short latencies (50
ms) by PHT.
PMID- 27489373
TI - Get the Diagnosis: an evidence-based medicine collaborative Wiki for diagnostic
test accuracy.
AB - BACKGROUND: Despite widespread calls for its use, there are challenges to the
implementation of evidence-based medicine (EBM) in clinical practice. METHODS: In
response to the challenges of finding timely, pertinent information on diagnostic
test accuracy, we developed an online, crowd-sourced Wiki on diagnostic test
accuracy called Get the Diagnosis (GTD, http://www.getthediagnosis.org). RESULTS:
Since its launch in November 2008 till October 2015, GTD has accumulated
information on 300 diagnoses, with 1617 total diagnostic entries. There are a
total of 1097 unique diagnostic tests with a mean of 5.4 tests (range 0-38) per
diagnosis. 73% of entries (1182 of 1617) have an associated sensitivity and
specificity and 89% of entries (1432 of 1617) have associated peer-reviewed
literature citations. Altogether, GTD contains 474 unique literature citations.
For a sample of three diagnoses, the search precision (percentage of relevant
results in the first 30 entries) in GTD was 100% as compared with a range of
13.3%-63.3% for PubMed and between 6.7% and 76.7% for Google Scholar. CONCLUSION:
GTD offers a fast, precise and efficient way to look up diagnostic test accuracy.
On three selected examples, GTD had a greater precision rate compared with PubMed
and Google Scholar in identifying diagnostic test information. GTD is a free
resource that complements other currently available resources.
PMID- 27489372
TI - Timeliness of referral of children with new onset type 1 diabetes.
AB - INTRODUCTION: Type 1 diabetes (T1D) is characterised by autoimmune destruction of
pancreatic beta cells leading to insulin deficiency. Prompt referral to a
specialist paediatric diabetes team (PDT) for insulin initiation and further
management is important to prevent diabetic ketoacidosis (DKA), which remains the
most common cause of death in this condition. OBJECTIVE: The aim was to study the
timeliness of referrals from general practitioners (GPs) to PDT, of children
suspected of having TID. METHOD: We carried out a survey of the practice of GPs
when they suspect TID in a young person, to investigate whether they recognised
the need for urgent referral to PDT. In addition, we carried out retrospective
case notes review of children diagnosed with diabetes mellitus between January
2005 and December 2014. RESULTS: 111/300 (37%) of GPs replied to survey. Of
these, 73/111 (65.8%) would have referred promptly to the PDT in accordance with
National Guidelines. However, 34.2% would have taken an action that would have
led to delay in referral to PDT. 96 children were diagnosed with TID during the
audit period. There was a delay in referral in 35 (36.5%) children. 19/35 (54.3%)
of these children presented with DKA. Mean duration of delay in presentation to
the PDT was 1.8 days. In both survey and audit, the most common reason for
delayed referral was GP attempting to confirm the diagnosis by undertaking
further diagnostic tests. CONCLUSIONS: Our study has identified a modifiable
reason for delayed referrals of children with TID.
PMID- 27489374
TI - Occlusive retinal vasculitis secondary to Behcet's disease.
PMID- 27489375
TI - Clinicopathological and prognostic significance of survivin expression in renal
cancer patients: a meta-analysis.
AB - BACKGROUND: Survivin has been reported to play a role in the diagnosis and
prognosis of renal cell carcinoma (RCC); however, published data on this subject
are conflicting. AIM: To conduct a meta-analysis to evaluate the impact of
survivin as a prognostic marker and its association with clinicopathological
variables in patients with RCC. METHOD: Comprehensive searches of electronic
databases (PubMed, ISI Web of Knowledge Embase, Google Scholar Web and the
Cochrane Library) were updated to June 2016 to retrieve eligible studies. The
association strength was measured with relative risks (RRs) and pooled HRs with
95% CIs, which were extracted and pooled to determine the association between
survivin expression and patient survival and clinicopathological features.
RESULTS: Ten studies with 1063 cases of RCC were included. Positive survivin
expression in RCC was associated with the TNM stage (pooled RR 1.49; 95% CI 1.07
to 2.07) or Fuhrman grade (pooled RR 1.63; 95% CI 1.15 to 2.32) in patients. The
correlation between survivin expression and gender was not significant (pooled RR
0.97; 95% CI 0.83 to 1.15). In addition, a considerable association was found
between survivin expression and overall survival for patients with RCC (pooled HR
1.94; 95% CI 1.24 to 3.05 (multivariate model) and 5.41; 95% CI 4.08 to 7.17
(univariate model)). CONCLUSIONS: Our results indicate that survivin is of
prognostic significance in patients with RCC.
PMID- 27489376
TI - Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders.
AB - Fecal microbiota transplantation has a 1700-year history. This forgotten
treatment method has been put into use again during the last 50 years. The
interest in microbiota-gut-brain axis and fecal microbiota transplantation is
rapidly increasing. New evidence is obtained in the etiopathogenesis of
neuropsychiatric disorders. There is a large number of experimental and clinical
researches in the field of gut-brain axis. There is limited information on fecal
microbiota transplantation. Despite this, initial results are promising. It is
commonly used in the treatment of gastrointestinal diseases such as Clostridium
difficile infection, Crohn's disease, ulcerative colitis. It is also
experimentally used in the treatment of metabolic and autoimmune diseases. There
are case reports that it is effective in the treatment of autism, Parkinson's
disease, multiple sclerosis, chronic fatigue syndrome and irritable bowel
syndrome. Its implementation is easy, and it is a cheap and reliable treatment
method. However, the long-term risks are unknown. Additionally, standard
application protocols have not yet been established. There are a lot of questions
to be answered. A university in Turkey has got official permission this year, and
started to apply fecal microbiota transplantation. In this review,
neuropsychiatric areas of use of fecal microbiota transplantation have been
discussed in the light of the current information.
PMID- 27489378
TI - Association of Polymorphisms within the Serotonin Receptor Genes 5-HTR1A, 5
HTR1B, 5-HTR2A and 5-HTR2C and Migraine Susceptibility in a Turkish Population.
AB - OBJECTIVE: Migraine, a highly prevelant headache disorder, is regarded as a
polygenic multifactorial disease. Serotonin (5-HT) and their respective receptors
have been implicated in the patogenesis. METHODS: We investigated the 5-HT1A, 5
HT1B, 5-HT2A, and 5-HT2C receptor gene polymorphisms and their association with
migraine in Turkish patients. The rs6295, rs1300060, rs1228814, rs6311, rs6313,
rs6314, rs6318, rs3813929 (-759C/T) and rs518147 polymorphisms were analyzed in
135 patients with migraine and 139 healthy subjects, using a BioMark 96.96
dynamic array system. RESULTS: We found no difference in the frequency of the
analyzed eight out of nine polymorpisms between migraine and control groups.
However, a significant association was found between the rs3813929 polymorphism
in the promoter region of 5-HTR2C gene and migraine. Also, the allele of
rs3813929 was more common in the migraine group. CONCLUSION: This result suggests
that the 5-HTR2C rs3813929 polymorphism can be a genetic risk factor for migraine
in a Turkish population.
PMID- 27489377
TI - Effects of Antipsychotics on Bone Mineral Density in Patients with Schizophrenia:
Gender Differences.
AB - Low bone mineral density (BMD) and osteoporosis are common in patients with
schizophrenia and detrimental to illness prognosis and life quality. Although the
pathogenesis is not fully clear, series of studies have revealed factors related
to low BMD such as life style, psychotic symptoms, medication use and the
activity of bone absorption markers. It has been known that antipsychotic-induced
hyperprolactinemia plays a critical role on decreased BMD. However, it remains
uncertain whether the risk factors differ between men and women. According to the
effect on prolactin, antipsychotics can be classified into two groups: prolactin
sparing (PS) and prolactin-raising (PR). Our previous study has demonstrated that
clozapine which is among the PS antipsychotics is beneficial for BMD when
compared with PR antipsychotics in women with chronic schizophrenia. We have also
found that risks factors associated with low BMD are different between men and
women, suggesting that gender-specific risk factors should be considered for
intervention of bone loss in patients with schizophrenia. This article reviews
the effects of antipsychotics use on BMD with particular discussion for the
differences on gender and age, which implicate the alterations of sex and other
related hormones. In addition, currently reported protective and risk factors, as
well as the effects of medication use on BMD including the combination of
antipsychotics and other psychotropic agents and other potential medications are
also reviewed.
PMID- 27489379
TI - Investigation of Dysregulation of Several MicroRNAs in Peripheral Blood of
Schizophrenia Patients.
AB - OBJECTIVE: The prevalence of schizophrenia is 1%, and it is a debilitating
disorder that often results in a shortened lifespan. Peripheral blood samples are
good candidates to investigate because they can be easily drawn, and they are
widely studied in psychiatric disorders. MicroRNAs are small non-coding RNA
transcripts. They regulate the expression of genes by binding to the 3'
untranslated region (UTR) of mRNAs and pointing them to degrade. In this study,
we aimed to investigate the expression of miR-9-5p, miR-29a-3p, miR-106-5p, miR
106b-5p, miR-107, miR-125a-3p, and miR-125b-3p in schizophrenia patients and
healthy controls. METHODS: We collected blood samples from 16 patients with
schizophrenia and 16 healthy controls. MicroRNAs were measured with reverse
transcriptase polymerase chain reaction. RESULTS: Schizophrenia patients showed
statistically significant upregulation of five microRNAs: miR9-5p (p=0.002),
miR29a-3p (p<0.001), miR106b-5p (p=0.002), miR125a-3p (p<0.001), and miR125b-3p
(p=0.018). CONCLUSION: Our results increased the value of the miR106 and miR29
families as potentially and consistently dysregulated in psychiatric disorders.
Our results should be considered preliminary, and they need confirmation in
future studies with larger sample sizes.
PMID- 27489380
TI - Efficacy and Tolerability of Paliperidone Extended-release in the Treatment of
First-episode Psychosis: An Eight-week, Open-label, Multicenter Trial.
AB - OBJECTIVE: We investigated the efficacy and tolerability of paliperidone extended
release (ER) tablets in patients with first-episode psychosis (n=75). METHODS:
This was an 8-week, open-label, multicenter trial. The primary outcome variable
was scores on the Positive and Negative Syndrome Scale (PANSS); secondary
measures included the Scale for the Assessment of Negative Symptoms (SANS), the
Cognitive Assessment Interview (CAI), and the Global Assessment of Functioning
(GAF). To assess safety, we measured drug-related adverse events, weight, lipid
related variables, and prolactin and administered the Simpson-Angus Rating Scale
(SARS), the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia
Scale (BAS), the Arizona Sexual Experiences Scale (ASEX), and the Udvalg for
Kliniske Undersogelser side effect rating scale (UKU). RESULTS: The
administration of paliperidone ER resulted in significant improvement in the
PANSS, SANS, CAI, and GAF scores (p<0.001) over time. This improvement was
evident as early as 1 week. The most frequent adverse events were akathisia,
somnolence, anxiety, and sedation, which were well tolerated. Modest increases in
weight and lipid profiles were also noted. Prolactin levels were substantially
increased at the endpoint in both male and female patients. CONCLUSION: These
results indicate that paliperidone ER is effective and is characterized by good
tolerability in the treatment of positive and negative symptoms and cognitive
functioning in first-episode psychosis.
PMID- 27489381
TI - Gender-specific Associations of the Brain-derived Neurotrophic Factor Val66Met
Polymorphism with Neurocognitive and Clinical Features in Schizophrenia.
AB - OBJECTIVE: To explore associations of the brain-derived neurotrophic factor
(BDNF) Val66Met polymorphism with cognitive functioning and psychopathology in
patients with schizophrenia. METHODS: We included 133 subjects meeting the DSM-IV
criteria for schizophrenia who were in the post-acute stage of the disease. BDNF
Val66Met genotypes were identified via polymerase chain reaction. The
computerized neurocognitive function battery, Positive and Negative Syndrome
Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Social and
Occupational Functioning Scale (SOFAS), and the Subjective Well-being under
Neuroleptic Treatment (SWN-K) were administered. Gender-stratified sub-analysis
was also conducted to identify gender-specific patterns in the findings. RESULTS:
In male patients, no significant difference in any measure by BDNF genotype was
evident. In female patients, scores on the CDSS and total PANSS and all subscales
were significantly higher in valine (Val) carriers. In addition, scores on the
SOFAS and SWN-K were significantly lower in Val carriers. In terms of
neurocognitive measures, female patients with the Val allele had significantly
poorer reaction times and fewer correct responses on the Continuous Performance
Test (CPT) and the Trail Making Test (Parts A and B). After adjustment of PANSS
total scores and log-transformed CDSS scores, CPT outcomes were significantly
poorer in female patients with than in those without the Val allele. CONCLUSION:
Gender-specific associations of the Val allele with poor neurocognitive function
and more severe psychopathology were evident. Further studies are required to
explore the mechanisms of these differences and the potential utility of the BDNF
genotype as a predictor of outcome in patients with schizophrenia.
PMID- 27489382
TI - Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory
Impairment in Mice.
AB - OBJECTIVE: We investigated the differential effects of the antipsychotic drugs
olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis
in mice. METHODS: MK-801 (0.1 mg/kg) was administered 20 minutes prior to
behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment,
either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40
minutes prior to MK-801 for the final 4 days. Spatial memory performance was
measured using a Morris water maze (MWM) test for 9 days (four trials/day).
Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn
cells labeled in tissue sections from the dentate gyrus of the hippocampus.
RESULTS: MK-801 administration over 9 days significantly impaired memory
performance in the MWM test compared to untreated controls (p<0.05) and these
deficits were blocked by treatment with olanzapine (p<0.05) but not haloperidol.
The administration of MK-801 also resulted in a decrease in the number of BrdU
labeled cells in the dentate gyrus (28.6%; p<0.01), which was prevented by
treatment with olanzapine (p<0.05) but not haloperidol. CONCLUSION: These results
suggest that olanzapine has a protective effect against cognitive impairments
induced by MK-801 in mice via the stimulating effects of neurogenesis.
PMID- 27489383
TI - A Questionnaire-based Study of the Views of Schizophrenia Patients and
Psychiatric Healthcare Professionals in Japan about the Side Effects of
Clozapine.
AB - OBJECTIVE: It is well documented that clozapine treatment causes agranulocytosis,
but it can also induce drowsiness, constipation, and hypersalivation; however,
these symptoms are usually less severe. It has been reported that clozapine
treated patients with schizophrenia and psychiatric healthcare professionals
consider different side effects to be important. The aim of this study was to
assess current practice related to the side effects of clozapine in clozapine
treated patients with schizophrenia and psychiatric healthcare professionals in
Japan. METHODS: Data were collected from January 2014 to August 2015 in Okehazama
Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated
patients with schizophrenia and psychiatric healthcare professionals
(psychiatrists and pharmacists) were enrolled in this study. RESULTS: Of the 106
patients and 120 psychiatric healthcare professionals screened, 100 patients and
104 healthcare professionals were included in this study. We asked the patients
what side effects caused them trouble and we asked psychiatric healthcare
professionals what side effects caused them concern. The patients and
psychiatrists held similarly positive views regarding the efficacy of clozapine.
The healthcare professionals were concerned about agranulocytosis (92.4%), blood
routines (61.3%). On the other hand, the patients experienced hypersalivation
(76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between
patient satisfaction and DAI-10 score. CONCLUSION: Patients experienced more
problems than healthcare professionals expected. However, usage experience of
clozapine healthcare professionals tended to have similar results to patients. It
is necessary that all healthcare professionals fully understand the efficacy and
potential side effects of clozapine. This is very important for promoting
clozapine treatment in Japan.
PMID- 27489385
TI - Zolpidem Induced Sleep-related Eating and Complex Behaviors in a Patient with
Obstructive Sleep Apnea and Restless Legs Syndrome.
AB - Zolpidem-induced sleep-related complex behaviors (SRCB) with anterograde amnesia
have been reported. We describe herein a case in which the development of
zolpidem-induced sleep-related eating disorder (SRED) and SRCB was strongly
suspected. A 71-year-old Korean male was admitted to the Department of Psychiatry
due to his repetitive SRED and SRCB with anterograde amnesia, which he reported
as having occurred since taking zolpidem. The patient also had restless legs
syndrome (RLS) and obstructive sleep apnea (OSA). His baseline serum iron level
was low at admission. Zolpidem discontinuation resulted in the immediate
disappearance of his SRED, but did not affect his RLS symptoms. These symptoms
rapidly improved after adding a single i.v. iron injection once daily, and so he
was discharged to day-clinic treatment. These findings indicate that zolpidem can
induce SRCB. Although the pathophysiology of zolpidem-induced SRED and other SRCB
remains unclear, clinicians should carefully monitor for the potential induction
of complex behaviors associated with zolpidem in patients with comorbid RLS or
OSA.
PMID- 27489384
TI - Opioid Analgesics and Depressive Symptoms in Burn Patients: What Is the Real
Relationship?
AB - OBJECTIVE: Major burn injuries are strongly associated with both psychological
trauma and severe pain, and opioids are the mainstay analgesics for the treatment
of severe burn pain. The objectives of this study are to find the complex
relationship between opioid dose, depression, and post-traumatic stress disorder
(PTSD) symptoms during the acute management of pain in burn patients. METHODS:
The symptoms of depression and PTSD were assessed in 43 burn patients immediately
following wound stabilization and 2 weeks after the initial evaluation. RESULTS:
Total opioid doses and Hamilton Depression Scale (HAMD) scores obtained during
the second evaluation were positively but weakly correlated after controlling for
age and total burn surface area (R=0.33, p=0.03). Moreover, pain management with
opioids was significantly more common in burn patients with low Clinician
Administered PTSD Scale scores (evaluation 1) and high HAMD scores (evaluation 2)
(F=6.66, p=0.001). CONCLUSION: High opioid dose following acute burn trauma might
have correlation with depressive symptoms. Monitoring of depressive symptoms may
be important following acute burn trauma and consequent opioids pain management,
particularly when PTSD symptoms appear minimal during the early stabilization of
patients.
PMID- 27489386
TI - Psychosis, Treatment Emergent Extrapyramidal Events, and Subsequent Onset of
Huntington's Disease: A Case Report and Review of the Literature.
AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
characterized by a triad of progressive motor dysfunction, cognitive decline and
psychiatric disturbances. The hallmark of HD is the distinctive choreiform
movement disorder that typically has a subtle, insidious onset in the fourth to
fifth decade of life and gradually worsens over 10 to 20 years until death.
Notably, two-thirds of HD patients present with chorea and one third with mental
changes. The prevalence of psychiatric symptoms is significantly higher than in
the general population, and is estimated to be around 66-73%. Here, we report a
unique case of subsequent onset of HD in a patient previously treated for
schizophrenia and complicated by the extrapyramidal side effects to
antipsychotics.
PMID- 27489387
TI - Clinical Usefulness of Aripiprazole and Lamotrigine in Schizoaffective
Presentation of Tuberous Sclerosis.
AB - Tuberous sclerosis is not as rare as once thought and has high psychiatric
comorbidities. However, bipolar or psychotic features associated with tuberous
sclerosis have been rarely reported. This report first presents a tuberous
sclerosis patient, resembling a schizoaffective disorder of bipolar type. A
patient with known tuberous sclerosis displayed mood fluctuation and psychotic
features. Her symptoms did not remit along with several psychiatric medications.
After hospitalization, the patient responded well with lamotrigine and
aripiprazole without exacerbation. As demonstrated in this case, tuberous
sclerosis may also encompass bipolar affective or psychotic features. We would
like to point out the necessity to consider bipolarity in evaluating and treating
tuberous sclerosis.
PMID- 27489388
TI - Dermatitis Artefacta Mimicking Borderline Personality Disorder: Sometimes, Skin
Could Be Misleading.
AB - Dermatitis artefacta lies in a gray zone, between the specialities of psychiatry
and dermatology. The condition could mimic a number of other lesions and
therefore is a source of much confusion in clinical practice. Here, we describe a
case of dermatitis artefacta in an 11-years old girl, which resembled self
harming behavior in Borderline personality disorder. We then discuss how the two
could be differentiated and why this becomes imperative while dealing with such
cases.
PMID- 27489389
TI - Manic Symptoms Due to Methylphenidate Use in an Adolescent with Traumatic Brain
Injury.
AB - Almost one-fifth of children who sustain a traumatic brain injury (TBI) are under
the risk of attention problems after injury. The efficacy and tolerability of
methylphenidate (MPH) in children with a history of TBI have not been completely
identified. In this case report, MPH-induced manic symptoms in an adolescent with
TBI will be summarized. A male patient aged 17 years was admitted with the
complaints of attention difficulties on schoolwork and forgetfullness which
became evident after TBI. Long-acting MPH was administered with the dose of 18
mg/day for attention problems. After one week, patient presented with the
complaints of talking to himself, delusional thoughts, irritability and
sleeplessness. This case highlights the fact that therapeutic dose of MPH may
cause mania-like symptoms in children with TBI. Close monitarization and slow
dose titration are crucial when considering MPH in children with TBI.
PMID- 27489390
TI - Lithium Toxicity Following Vertical Sleeve Gastrectomy: A Case Report.
AB - We are presenting the first documented case of lithium toxicity after vertical
sleeve gastrectomy surgery in an 18 year-old female with psychiatric history of
bipolar disorder who was treated with lithium. This case illustrates the need for
closer monitoring of lithium levels following bariatric surgery. Both
psychiatrists and surgeons should be aware of the potential risk of lithium
toxicity following bariatric surgery, as well as the need to judiciously monitor
lithium level and possibly adjust the dose of some medications.
PMID- 27489391
TI - Impact of High Dose Lorazepam on Seizure Threshold in Catatonia: Experience from
a Case Study.
PMID- 27489392
TI - A Case of May-Thurner Syndrome.
AB - May-Thurner syndrome is the condition of the left common iliac vein being
compressed between the right common iliac artery and the associated vertebral
body. This condition has been linked to spontaneous episodes of deep vein
thrombosis (DVT), especially in women aged 20-50, and it may contribute to the
slightly higher tendency to develop left-sided (~56%) versus right-sided DVTs. A
50-year-old morbidly obese (BMI 42.7 kg/m2) female presented to the emergency
room with acute left leg pain. Past medical history included asthma. Patient is
employed as a helper in home health services; no recent history of travel and no
history suggestive of hereditary thrombophilia. Prior tobacco use was noted.
Patient was admitted to the medical floors and investigated for DVT. Ultrasound
Doppler imaging of both legs demonstrated left-sided occlusive DVT in the
popliteal, superficial femoral, common femoral veins with extension into the
external iliac vein. Imaging in the right leg was unremarkable. Patient was
treated with enoxaparin (Lovenox). A hypercoagulation panel was unremarkable. A
left lower extremity venogram showed a thrombus at the level of the common
femoral vein extending into the iliac vein with stasis of contrast within the
right external iliac vein. Following that, she had venoplasty and thrombolytic
therapy. The next day, she underwent left iliofemoral mechanical thrombectomy,
venoplasty, and left common iliac vein stenting. After an uneventful recovery,
the patient was discharged on rivaroxaban for 3 months. In summary, while this
patient was initially thought to have unprovoked DVT, absence of any
hypercoagulable disorders and the findings in venogram favored the diagnosis of
May-Thurner syndrome. For women in this age group with this type of presentation,
this is an important diagnosis to keep in mind.
PMID- 27489393
TI - Urban family reconstitution-a worked example.
AB - Family reconstitutions have been undertaken only rarely in urban settings due to
the high mobility of historical urban populations, in both life and death.
Recently Gill Newton has outlined a methodology for the reconstitution of urban
populations and we applied a modified version of this method to the large
Westminster parish of St. Martin in the Fields between 1752 and 1812, a period
that posed particular difficulties for family reconstitution because of the rapid
lengthening of the interval between birth and baptism.1 The extraordinary
richness of the records for St. Martin in the Fields made it possible to
investigate burial and baptismal practices in great detail, and the extent and
impact of residential mobility. We found that short-range, inter-parochial
movement was so frequent that it was necessary to confine the reconstitution
sample to windows in which families registered events at a single street address.
Using birth interval analysis and the frequencies of twin births it was possible
to demonstrate that the registration of birth events was fairly complete, but
that many infant and child burials were missed. These missing burials probably
resulted from the unreported export of corpses for burial in other parishes, a
phenomenon for which we had considerable evidence. The limitations of family
reconstitution in this highly mobile and heterogeneous urban population is
discussed and we demonstrate some checks and corrections that can be used to
improve the quality of such reconstitutions.
PMID- 27489394
TI - Understanding variability in crop response to fertilizer and amendments in sub
Saharan Africa.
AB - Improved understanding of soil fertility factors limiting crop productivity is
important to develop appropriate soil and nutrient management recommendations in
sub-Saharan Africa. Diagnostic trials were implemented in Kenya, Malawi, Mali,
Nigeria and Tanzania, as part of the African Soils Information Service (AfSIS)
project, to identify soil fertility constraints to crop production across various
cropping systems and soil fertility conditions. In each country, one to three
sites of 10 km * 10 km were included with each site having 12-31 field trials.
The treatments tested included a control, an NPK treatment, three treatments in
which the N, P and K nutrients were omitted one at a time from the NPK treatment,
and three treatments in which secondary and micronutrients (Ca, Mg, S, Zn and B)
simply referred here as multi-nutrients, manure and lime were added to the NPK.
The field trials were conducted for 1-2 seasons; the test crop was maize except
in Mali where sorghum was used. Nitrogen was limiting in all sites and generally
the most limiting nutrient except in Sidindi (Kenya) and Kontela (Mali) where P
was the most limiting. The general pattern in Kiberashi (Tanzania) shows none of
the nutrients were limiting. K is mainly limiting in only one site (Mbinga)
although incidences of K limitation were seen in almost all sites. Addition of
multi-nutrients and manure further improved the yields of NPK in most sites.
Cluster analyses revealed that maize crop in 11% of fields were highly responsive
to nitrogen application, 25% (i.e., 21% poor and 4% fertile) 'non-responsive' to
any nutrient or soil amendment, 28% being 'low responsive' and 36% of
'intermediate response'. This study indicates that constraints to crop production
vary considerably even within a site, and that addressing limitations in
secondary and micronutrients, and increasing soil carbon can improve response to
fertilizers. For sustainable crop production intensification in smallholder
farming systems in SSA, there is need to develop management strategies to improve
efficiency of fertilizer use and of other inputs, recognizing the site-specific
nutrient response patterns at various spatial scales.
PMID- 27489395
TI - Response of bean cultures' water use efficiency against climate warming in
semiarid regions of China.
AB - Farm crop growing and high efficiency water resource utilizing are directly
influenced by global warming, and a new challenge will be given to food and water
resource security. A simulation experiment by farm warming with infrared ray
radiator was carried out, and the result showed photosynthesis of broad bean was
significantly faster than transpiration during the seedling stage, ramifying
stage, budding stage, blooming stage and podding stage when the temperate was
increased by 0.5-1.5 degrees C. But broad bean transpiration was faster than
photosynthesis during the budding stage, blooming stage and podding stage when
the temperature was increased by 1.5 degrees C above. The number of grain per
hill and hundred-grain weight were significantly increased when the temperature
was increased by 0.5-1.0 degrees C. But they significantly dropped and finally
the yield decreased when the temperature was increased by 1.0 degrees C above.
The broad bean yield decreased by 39.2-88.4% when the temperature was increased
by 1.5-2.0 degrees C. The broad bean water use efficiency increased and then
decreased with temperature rising. The water use efficiency increased when the
temperature was increased by 1.0 degrees C below, and it quickly decreased when
the temperature was increased by 1.0 degrees C above. In all, global warming in
the future will significantly influence the growth, yield and water use
efficiency of bean cultures in China's semiarid regions.
PMID- 27489396
TI - International Classification of Functioning, Disability and Health in
Audiological Practices.
PMID- 27489397
TI - What Is the International Classification of Functioning, Disability and Health
and Why Is It Relevant to Audiology?
AB - The World Health Organization's International Classification of Functioning,
Disability and Health (ICF) is widely used in disability and health sectors as a
framework to describe the far-reaching effects of a range of health conditions on
individuals. This biopsychosocial framework can be used to describe the
experience of an individual in the components of body functions, body structures,
and activities and participation, and it considers the influence of contextual
factors (environmental and personal) on these components. Application of the ICF
in audiology allows the use of a common language between health care
professionals in both clinical and research settings. Furthermore, the ICF is
promoted as a means of facilitating patient-centered care. In this article, the
relevance and application of the ICF to audiology is described, along with
clinical examples of its application in the assessment and management of children
and adults with hearing loss. Importantly, the skills necessary for clinicians to
apply the ICF effectively are discussed.
PMID- 27489398
TI - The International Classification of Functioning, Disability and Health as a
Framework for Providing Patient- and Family-Centered Audiological Care for Older
Adults and Their Significant Others.
AB - Hearing impairment is highly prevalent in the older population, and it impacts
communication and quality of life for both the people with the hearing
difficulties and their significant others. In this article, typical audiological
assessment and management of an older adult is contrasted with a best practice
approach wherein the World Health Organization's International Classification of
Functioning, Disability and Health (ICF) framework is applied. The aim of the
comparison is to demonstrate how the ICF expands our focus: rather than merely
focusing on impairment, we also consider the activities, participation, and
contextual factors for both the person with the hearing impairment and his or her
family. A case example of an older patient and her spouse is provided, and their
shared experience of the patient's hearing impairment is mapped onto the ICF
framework. Family-centered hearing care is recommended for individualizing care
and improving outcomes for older patients and their families.
PMID- 27489399
TI - Hearing and Cognitive Impairment and the Role of the International Classification
of Functioning, Disability and Health as a Rehabilitation Framework.
AB - The International Classification of Functioning, Disability and Health (ICF) has
been applied widely in the literature to describe and differentiate the broad
implications of hearing impairment (HI) and cognitive impairment (CI) on
communication. As CI and HI are largely age-related conditions, the likelihood of
comorbidity of these conditions is high. In the context of an aging population,
the prevalence of comorbidity is likely to rise, yet much of the clinical
assessment and intervention in HI and CI occur separately. The benefit of
addressing the dual impact of these conditions is of increasing clinical
importance for all clinicians working with older adults and for audiologists and
speech pathologists in particular. In this article, the ICF model will be applied
to explore the everyday implications of HI and CI. Furthermore, the clinical
implications of the ICF model are explored with particular respect to
communication assessment and intervention options. The potential benefit of
combining activity- and participation-focused interventions currently offered for
HI and CI independently is examined.
PMID- 27489401
TI - Aphasia and Auditory Processing after Stroke through an International
Classification of Functioning, Disability and Health Lens.
AB - Aphasia is an acquired language impairment affecting speaking, listening,
reading, and writing. Aphasia occurs in about a third of patients who have
ischemic stroke and significantly affects functional recovery and return to work.
Stroke is more common in older individuals but also occurs in young adults and
children. Because people experiencing a stroke are typically aged between 65 and
84 years, hearing loss is common and can potentially interfere with
rehabilitation. There is some evidence for increased risk and greater severity of
sensorineural hearing loss in the stroke population and hence it has been
recommended that all people surviving a stroke should have a hearing test.
Auditory processing difficulties have also been reported poststroke. The
International Classification of Functioning, Disability and Health (ICF) can be
used as a basis for describing the effect of aphasia, hearing loss, and auditory
processing difficulties on activities and participation. Effects include reduced
participation in activities outside the home such as work and recreation and
difficulty engaging in social interaction and communicating needs. A case example
of a young man (M) in his 30s who experienced a left-hemisphere ischemic stroke
is presented. M has normal hearing sensitivity but has aphasia and auditory
processing difficulties based on behavioral and cortical evoked potential
measures. His principal goal is to return to work. Although auditory processing
difficulties (and hearing loss) are acknowledged in the literature, clinical
protocols typically do not specify routine assessment. The literature and the
case example presented here suggest a need for further research in this area and
a possible change in practice toward more routine assessment of auditory function
post-stroke.
PMID- 27489400
TI - The Application of the International Classification of Functioning, Disability
and Health to Functional Auditory Consequences of Mild Traumatic Brain Injury.
AB - This article reviews the auditory consequences of mild traumatic brain injury
(mTBI) within the context of the International Classification of Functioning,
Disability and Health (ICF). Because of growing awareness of mTBI as a public
health concern and the diverse and heterogeneous nature of the individual
consequences, it is important to provide audiologists and other health care
providers with a better understanding of potential implications in the assessment
of levels of function and disability for individual interdisciplinary remediation
planning. In consideration of body structures and function, the mechanisms of
injury that may result in peripheral or central auditory dysfunction in mTBI are
reviewed, along with a broader scope of effects of injury to the brain. The
activity limitations and participation restrictions that may affect assessment
and management in the context of an individual's personal factors and their
environment are considered. Finally, a review of management strategies for mTBI
from an audiological perspective as part of a multidisciplinary team is included.
PMID- 27489402
TI - Adolescents with Hearing Loss and the International Classification of
Functioning, Health, and Disability: Children & Youth Version.
AB - In 2007, the World Health Organization published a set of International
Classification of Functioning, Disability and Health (ICF) codes designed for
children and youth (ICF-CY version). The ICF-CY considers typical developmental
changes associated with childhood while describing health status and the effects
of intervention. In this article we will describe how a specific intervention
(transition planning for adolescents) can be documented with the ICF-CY.
Transition planning in health care prepares adolescents and their families for
the transfer from pediatric to adult health services and has been demonstrated to
be an effective practice for adolescents with many types of chronic health
conditions (e.g., cystic fibrosis, epilepsy, diabetes). Audiology has not yet
addressed transition planning for adolescents with hearing loss; therefore, we
propose using the ICF-CY to design a pathway of care. The ICF-CY can standardize
transition planning to the benefit of both teen patients and audiologists: teens
and their families would gradually acquire necessary knowledge and skills, and
audiologists would develop a meaningful data set to help further inform our
pediatric practices, as well as give more structure, depth, and accountability to
our role in rehabilitation.
PMID- 27489403
TI - Relevance of the International Classification of Functioning, Health and
Disability: Children & Youth Version in Early Hearing Detection and Intervention
Programs.
AB - Early hearing detection and intervention (EHDI) programs have been guided by
principles from the Joint Committee on Infant Hearing and an international
consensus of best practice principles for family-centered early intervention.
Both resources provide a solid foundation from which to design, implement, and
sustain a high-quality, family-centered EHDI program. As a result, infants born
with permanent hearing loss and their families will have the support they need to
develop communication skills. These families also will benefit from programs that
align with the framework offered by the World Health Organization's International
Classification of Functioning, Disability and Health: Children & Youth Version
(ICF-CY). Within this framework, health and functioning is defined and measured
by describing the consequences of the health condition (i.e., hearing loss) in
terms of body function, structures, activity, and participation as well as social
aspects of the child. This article describes the relevance of the ICF-CY for EHDI
programs and offers a modified approach by including aspects of quality of life
and human development across time.
PMID- 27489404
TI - The Role of the World Health Organization's International Classification of
Functioning, Health and Disability in Models of Infant Cochlear Implant
Management.
AB - Newborn hearing screening has led to the early diagnosis of hearing loss in
neonates and early device fitting is common, based primarily on
electrophysiologic and radiologic information, with some supplementary behavioral
measures. Such early fitting of hearing devices, in particular cochlear implants
(CIs), has been beneficial to the majority of children implanted under the age of
12 months who meet the cochlear implant candidacy criteria. Comorbidities are
common in children with hearing loss, although they may not be evident in
neonates and may not emerge until later in infants. Evidence suggests that the
child's outcomes are strongly influenced by a range of environmental factors
including emotional and social support from the immediate and extended family.
Consequently, such factors are important in service planning and service delivery
for babies and children receiving CIs. The World Health Organization's
International Classification of Functioning, Health and Disability (ICF) can
provide a framework to facilitate the holistic management of pediatric cochlear
implant recipients. The ICF also can be used to map the progress of recipients
over time to highlight emerging issues that require intervention. This article
will discuss our preliminary use of the ICF to establish clinical practice;
develop advocacy skills among clients and their families; identify eligibility
for services such as support in educational settings; enable access to modes of
service delivery such as telepractice; provide a conceptual framework for policy
and program development for pediatric cochlear implant recipients (i.e., in both
disability and health services); and, most importantly, establish a clear pathway
for the longitudinal management of the cochlear implant in a child's future. It
is anticipated that this model will be applied to other populations receiving
cochlear implants through our program.
PMID- 27489405
TI - Proton Dipolar Spin-Lattice Relaxation in Nano-channels of Natrolite.
AB - The 1H nuclear magnetic resonance (NMR) spectra and the dipolar spin-lattice
relaxation time T1D for 1H in the natural natrolite (Na2Al2Si3O10.2H2O) have been
measured in the temperature range of 190-390 K. From the temperature
transformations of 1H NMR spectra, it follows that at T > 300 K, the diffusion of
water molecules along the nano-channels is observed. From experimental T1D data,
it follows that the 180 degrees flip motion of the water molecules takes place
in natrolite. At low temperature (T < 250 K), the dipolar interaction with
paramagnetic impurities as a relaxation mechanism of 1H nuclei becomes
significant.
PMID- 27489406
TI - The journey of articular cartilage repair.
PMID- 27489407
TI - Concepts in regenerative medicine: Past, present, and future in articular
cartilage treatment.
AB - Regenerative medicine is emerging with great interest and hope from patients,
industry, academia, and medical professionals. Cartilage regeneration,
restoration, or repair is one of the prime targets that remains largely unsolved,
and many believe that regenerative medicine can possibly deliver solutions that
can be widely used to address the current gap(s) in treatment. In the United
States, Europe, Australia, and India the regulation of regenerative based
treatments has become a big debate. Although the rules and regulations remain
unclear, clinicians that are interested should carry-on with the best available
guidelines to ensure safety and compliance during delivery in clinical practice
to avoid regulatory infraction. Many have made significant investment of time,
resources, and facilities in recent years to provide new regenerative treatment
options and advance medical care for patients. Instead of reinventing the wheel,
it would be more efficient to adopt currently accepted standards and nomenclature
borrowed from transplantation science, and cord blood storage industries. The
purposes of this article are to provide some historical background to the field
of regenerative medicine as it applies to cartilage, and how this field has
developed. This will be followed by a separate discussion on regulatory oversight
and input and how it has influenced access to care. Furthermore, we discuss
current clinical techniques and progress, and ways to deliver these treatments to
patients safely, effectively, and in a cost sensitive manner, concluding with an
overview of some of the promising regenerative techniques specific to cartilage.
PMID- 27489408
TI - Microfracture for the treatment of cartilage defects in the knee joint - A golden
standard?
AB - The evidence for the effectiveness of the microfracture procedure is largely
derived from case series and few randomized trials. Clinical outcomes improve
with microfracture for the most part, but in some studies these effects are not
sustained. The quality of cartilage repair following microfracture is variable
and inconsistent due to unknown reasons. Younger patients have better clinical
outcomes and quality of cartilage repair than older patients. When lesion
location was shown to affect microfracture outcome, patients with lesions of the
femoral condyle have the best clinical improvements and quality of cartilage
repair compared with patients who had lesions in other areas. Patients with
smaller lesions have better clinical improvement than patients with larger
lesions. The necessity of long postoperative CPM and restricted weight bearing is
widely accepted but not completely supported by solid data. Maybe new
developments like the scaffold augmented microfracture(6) will show even more
consistent clinical and biological results as well as faster rehabilitation for
the treatment of small to medium sized cartilage defects in younger individuals.
All in all there is limited evidence that micro fracture should be accepted as
gold standard for the treatment of cartilage lesions in the knee joint. There is
no study available which compares empty controls or non-surgical
treatment/physiotherapy with microfracture. According to the literature there is
even evidence for self regeneration of cartilage lesions. The natural history of
damaged cartilage seems to be written e.g. by inflammatory processes, genetic
predisposition and other factors. Possibly that explains the large variety of the
clinical outcome after micro fracture and possibly the standard tools for
evaluation of new technologies (randomized controlled trials, case series, etc.)
are not sufficient (anymore). Future technologies will be evaluated by big data
from international registries for earlier detection of safety issues, for
detection of subtle but crucial co-factors for failure and osteoarthritis as well
as for lower financial burdens affecting industry and healthcare systems
likewise.
PMID- 27489409
TI - Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).
AB - Degenerative and traumatic articular cartilage defects are common, difficult to
treat, and progressive lesions that cause significant morbidity in the general
population. There have been multiple approaches to treat such lesions, including
arthroscopic debridement, microfracture, multiple drilling, osteochondral
transplantation and autologous chondrocyte implantation (ACI) that are currently
being used in clinical practice. Autologous bone-marrow mesenchymal cell induced
chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method
combines a modified microfracture technique with the application of a bone marrow
aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular
cartilage defects. We reviewed the current literatures and surgical techniques
for mesenchymal cell induced chondrogenesis.
PMID- 27489410
TI - Scaffold-free, stem cell-based cartilage repair.
AB - Various approaches to treat articular cartilage have been widely investigated due
to its poor intrinsic healing capacity. Stem cell-based therapy could be a
promising approach as an alternative to chondrocyte-based therapy and some of
these therapies have been already applied in clinical condition. This review
discusses the current development of stem cell-based therapies in cartilage
repair, specifically focusing on scaffold-free approaches.
PMID- 27489411
TI - Autologous collagen induced chondrogenesis (ACIC: Shetty-Kim technique) - A
matrix based acellular single stage arthroscopic cartilage repair technique.
AB - The defects of articular cartilage in the knee joint are a common degenerative
disease and currently there are several established techniques to treat this
problem, each with their own advantages and shortcomings. Autologous chondrocyte
implantation is the current gold standard but the technique is expensive, time
consuming and most versions require two stage procedures and an arthrotomy.
Autologous collagen induced chondrogenesis (ACIC) is a single-stage arthroscopic
procedure and we developed. This method uses microfracture technique with
atelocollagen mixed with fibrin gel to treat articular cartilage defects. We
introduce this ACIC techniques and its scientific background.
PMID- 27489412
TI - Non-operative management of osteoarthritis of the knee joint.
AB - Osteoarthritis is a chronic disorder of synovial joints in which there is
progressive softening and disintegration of articular cartilage accompanied by
the growth of osteophytes. Treatment designed for osteoarthritis should aim at
reducing pain, improve joint mobility, and limit functional impairment. It can be
achieved by pharmacological and non-pharmacological means. Non-operative
treatment of OA is useful for patients with KL grade 1-3, which are early stages
of OA. However, in an advanced stage of OA (KL grade 4), surgical treatment is
needed as definitive treatment.
PMID- 27489413
TI - Mesenchymal stem cell therapy for osteoarthritis.
AB - The versatility of mesenchymal stem cells (MSCs) as a treatment modality has
landed it another repair target: osteoarthritis, a crippling cartilage disease
that frequently afflicts the aged population. Through many studies, this newly
discovered method has been shown to significantly alleviate the pain experienced
by osteoarthritic patients. Notwithstanding the effectiveness of MSCs in this
regard, varying degrees of success rates have also been reported, which is
probably attributable to the different approaches adopted in harnessing MSCs'
therapeutic value. Accordingly, it is pertinent to understand the contributory
factors like MSC type, dosage, size of osteoarthritic lesion, MSC carrier, and
mode of infusion, which would be briefly discussed in this review.
PMID- 27489414
TI - 2016 barriers to cartilage restoration.
AB - Cartilage restoration has flourished since the 1990s. The early pioneering work
included cell therapy by Peterson, marrow stimulation by Johnson, osteochondral
autograft treatments by Hangody, and osteochondral allografts by Gross. Since
those early days, many scientists and clinicians have created "variations on a
theme", markedly expanding the potential options for treating patients with
symptomatic chondral lesions. Nevertheless, a variety of barriers exist between
these new cartilage products and their clinical applications. These barriers may
be categorized as cost, regulatory, insurance, and logistical issues. While
absolute solutions will remain elusive, the current goal is to define these
barriers as the first step toward solving these problems.
PMID- 27489415
TI - Acute anterior cruciate ligament injuries in multisport elite players:
Demography, association, and pattern in different sports.
AB - BACKGROUND: Anterior cruciate ligament (ACL) tear rates are known to vary from
sport to sport. To the best of our knowledge, the relationship of ACL injury with
different sports is not reported earlier. The objective of the present study is
to investigate the association of ACL injury with different sports and to
document various associated ligamentous, meniscal, and chondral lesions of the
knee. MATERIALS AND METHODS: Descriptive epidemiological study was carried out in
a tertiary care center over a 10-year period. Data were collected of the 638 ACL
injured elite sportspersons operated by us. Percentage of ACL injuries and other
associated injuries of the knee in different games was calculated. Chi-square
test was applied to analyze the relationship between injuries of the specific
structures of knee and sports played. p values less than 0.05 were considered to
be statistically significant with a confidence interval of 95%. RESULTS: Kabaddi
and football constituted the highest percentage (61%) of ACL injuries. Associated
injuries were 10 posterior cruciate ligament tears, 11 posterolateral corner
injuries, three medial collateral ligament tears, 390 meniscal tears (206 medial,
184 lateral), 201 femoral/tibial condylar lesions (128 medial, 40 lateral femoral
condyle and 17 medial, 16 lateral tibial condyle), and two common peroneal nerve
injuries. Lateral meniscal tears in kabaddi and medial femoral condylar lesions
in badminton were significantly higher. CONCLUSIONS: Kabaddi resulted in higher
number of ACL injuries and other associated injuries to the knee. Further
investigation is required to ascertain high-risk factors for such injuries.
PMID- 27489416
TI - Current practice variations in the management of anterior cruciate ligament
injuries in Delhi.
AB - BACKGROUND: The aim of this study was to determine the current practices and
preferences of the arthroscopic surgeons of Delhi in the diagnosis, treatment and
rehabilitation of patients with anterior cruciate ligament (ACL) injury. METHODS:
It was a cross-sectional descriptive study conducted among arthroscopic surgeons
of Delhi. A survey was conducted using a questionnaire that was sent either by e
mail or by direct contact to all sixty arthroscopic surgeons of Delhi. RESULTS:
Forty-eight (80%) surgeons responded to our questionnaire. Maximum participants
(83.3%) used semitendinosus/gracilis tendon autograft for ACL reconstruction
(ACLR) and only 2.1% were using bone-patellar-tendon-bone (BPTB) autograft. Most
preferred method of graft fixation was an 'interference screw' on the tibial side
and an 'endobutton' on the femoral side, which was preferred by 95.83% and 93.75%
surgeons, respectively. Almost all respondents (97%) used a bio-absorbable
interference screw for tibial side graft fixation. Postoperative bracing was
advised for <3 weeks by 47.9% surgeons and for 3-6 weeks by 31.3%. The results
were analysed using statistical analysis. CONCLUSION: Surgeon preferences in ACLR
differ considerably among the arthroscopic surgeons of Delhi. There is majority
consensus for using Hamstring autograft (single bundle) with a suspensory
fixation on the femoral side and an aperture fixation on the tibial side.
Transportal technique of making the femoral tunnel and preservation of amputation
stump were the preferred methods. However, differences exist over the timing of
surgery, rehab after surgery, pain management, etc.
PMID- 27489418
TI - Epidemiological profile of sports-related knee injuries in northern India: An
observational study at a tertiary care centre.
AB - BACKGROUND: Sports-related knee injuries occur commonly in athletes. However,
there is no published epidemiological study from India till date. OBJECTIVES: The
purpose of this study was to identify common injuries sustained by Indian
athletes participating in different sports and to study various associated
demographic features. A secondary objective was to investigate different factors,
which may affect return to sport by the athlete. STUDY DESIGN: Cross-sectional
study (observational study). STUDY CENTRE: Sports injury clinic, PGIMER,
Chandigarh. METHODS: Out of 465 athletes who presented to us with sports-related
knee injuries over a 5-year period, 363 athletes (from 24 different sports) with
complete records were identified. Data were analysed for demographic features,
type of sport, mechanism of injury, injury scenario, athlete's level of play,
injury duration at presentation, injury patterns and type of management.
Telephonic interviews were conducted with each athlete to enquire about return to
sport and time lost in sport due to the knee injury. Factors associated with
return to sport were investigated using statistical tests of association.
RESULTS: Soccer was found to be the most common sport associated with knee
injuries accounting for 30.6% of the injuries followed by kabaddi (20.9%). The
most common mechanism was non-contact injury (64.4%). Competitive injuries were
found to be significantly more than practice/training injuries (p < 0.0001). The
most common injuries noted were ACL tears (n = 314) followed by meniscus injuries
(n = 284) and the most common combination of injuries were an ACL tear with
medial meniscus tear (n = 163). Only 39.8% of the athletes returned to sport.
Mean duration of time lost in sport among those who returned to sport was 8.84
months. Return to sport was significantly associated with body mass index, level
of competitiveness of the athlete and type of management (p = 0.017, 0.045 and
<0.0001, respectively). CONCLUSION: Knee injuries take a huge toll on an
athlete's career as observed in this study. Prevention of knee injuries is of
paramount importance and more focussed epidemiological studies are needed for
formulating policies to prevent sports injuries in both professional and amateur
athletes. LEVEL OF EVIDENCE: IV.
PMID- 27489417
TI - Comparative analysis of arthroscopic debridement in osseous versus soft tissue
anterior ankle impingement.
AB - BACKGROUND: Arthroscopic debridement has been a gold standard procedure for
anterior ankle impingement, both in cases of osseous and soft tissue impingement.
There is sparse literature on comparative outcome with respect to functional
results between the two types of impingement post-arthroscopic debridement.
METHODS: Our study included 14 patients diagnosed as cases of anterior ankle
impingement on the basis of clinical and radiological examination. They were
segregated into two groups (on the basis of cause of impingement (osseous versus
soft tissue)). Both groups were treated by arthroscopic debridement. Primary
outcome was patient satisfaction, which was assessed by Likert scale and clinical
outcomes were measured using AOFAS ankle-hind foot scale, VAS score, range of
motion and time to return to pre-injury activity level in both groups. RESULTS:
Mean follow-up was of 15 months where eleven patients reported an excellent
recovery, two patients had good recovery while one patient reported poor outcome.
Mean AOFAS ankle hind foot scale improved from 50.5 preoperatively to 85.71
postoperatively (statistically significant; p value - 0.0001). Mean Likert scale
value post-operative was 4.21. VAS score showed significant improvement in
patients of both the groups. Range of motion was slightly better in soft tissue
impingement type with a relatively shorter time to return to sports or preinjury
activity level as compared to osseous impingement group. CONCLUSIONS: The
patients in both the groups had comparable outcomes with no statistically
significant difference with regard to patient satisfaction and clinical outcome.
PMID- 27489419
TI - Loose body as an obstacle for posterolateral arthroscopic portal formation in the
knee joint.
AB - In this report, we present a case with difficult arthroscopic posterolateral
portal formation due to loose body located in posterior compartment. These loose
bodies are responsible for pain, decreased range of motion and cartilage damage
in the knee joint. By making the posterior trans-septal portal prior,
posterolateral portal could be made without difficulty completing the planned
arthroscopic procedure.
PMID- 27489420
TI - Finger trapped in door latch removed using an electric saw. A new technique and
review of other techniques.
AB - Trapping of fingers in metallic bands is a commonly encountered situation. The
children, elderly people, and psychiatric patients are the usual victims. The
constricting object in the digit causes obstruction to lymphatic and venous
drainage leading to oedema distal to the constriction, which leads to further
neurovascular compromise and presents as a surgical emergency. A 7-year-old boy
presented to us with his right middle finger being stuck in a steel door latch.
Multiple attempts were made to remove the trapped finger with conventional
methods, and subsequently, it was removed by electric-driven metal cutting saw,
which was not previously described in medical literature to the best of our
knowledge.
PMID- 27489421
TI - Clinical Characteristics of Odontogenic Cutaneous Fistulas.
AB - BACKGROUND: Odontogenic cutaneous fistula appears as dimpling or a nodule with
purulent discharge, usually in the chin or jaw. Affected patients usually seek
help from dermatologists or surgeons rather than from dentists. However, clinical
symptoms of facial skin fistula without dental problems can lead to misdiagnosis.
OBJECTIVE: The purpose of this study was to investigate the clinical
characteristics of patients with odontogenic cutaneous fistulas. METHODS: This
retrospective observational study was performed at Chungbuk National University
Hospital by analyzing patients who visited from April 1994 to September 2014.
Following clinical and radiographic examinations, the paths and origins of sinus
fistulas were determined. Investigated factors were gender, age, morphology,
location, originating tooth, time to evolution, recurrence, and treatment method.
RESULTS: Thirty-three patients (22 males, 11 females; average age 49.2 years)
were examined during the investigation period. Thirty-four fistulas were
diagnosed as odontogenic cutaneous fistulas. The most common morphology was
dimpling (n=14, 41.2%). The various locations observed were related to the
originating tooth. The most common site was the mandibular body related to
mandibular molars. The referral clinical diagnosis was of odontogenic origin in 6
cases (18.2%). The majority of patients had experienced recurrence after
treatment in previous clinics that had failed to diagnose odontogenic cutaneous
fistula. Surgical fistulectomy and/or tooth treatment were performed in all
cases. All patients were followed-up for 1 year. None showed signs of recurrence.
CONCLUSION: Extraoral and dental examinations are required to make a diagnosis of
odontogenic cutaneous fistula. Thus, cooperation between dermatologists and
dentists is essential.
PMID- 27489422
TI - Relation between the Peripherofacial Psoriasis and Scalp Psoriasis.
AB - BACKGROUND: Facial involvement of psoriasis is known to be one of the clinical
manifestations that indicate the severity of the psoriasis and thought to be more
closely associated with certain distribution. Centrofacial (CF) psoriasis has
been suggested to be related with severity of systemic disease while
peripherofacial (PF) psoriasis has been thought to have connection with scalp
psoriasis. OBJECTIVE: To analyze the epidemiologic characteristics, clinical
features and subjective feelings of patients with facial psoriasis and to find
out relationship between scalp psoriasis and facial involvement according to the
facial types. METHODS: One hundred nineteen facial psoriasis patients were
categorized into 3 types according to the distribution: PF type, CF type and
mixed facial (MF) type. Onset and duration of facial and scalp psoriasis, and
their relationship were questioned. Severity and extent of psoriasis on whole
body, face, and scalp were rated by clinicians. RESULTS: There was no significant
difference of whole body psoriasis area and severity index (PASI) and body
surface area (BSA) score but scalp PASI and BSA was much higher in PF psoriasis
compared to CF psoriasis (scalp PASI, 17.9 vs. 10.1; p=0.005) (scalp BSA, 40.9
vs. 22.2; p=0.002). According to the questionnaire, patient's objective feeling
about the spreading of scalp lesion to facial area was markedly more prominent in
the patients with peripheral involvement (PF+MF, 90.1%; CF, 54.2%; p<0.0001).
CONCLUSION: Among subtypes of facial psoriasis, PF psoriasis is closely
associated with spreading of scalp lesion into the face rather than reflecting
the disease severity.
PMID- 27489423
TI - Histopathological Differential Diagnosis of Psoriasis and Seborrheic Dermatitis
of the Scalp.
AB - BACKGROUND: The differential diagnosis of psoriasis and seborrheic dermatitis can
be difficult when both conditions are localized to the scalp without the
involvement of other skin sites. OBJECTIVE: We aimed to evaluate the
histopathological differences between psoriasis and seborrheic dermatitis on the
scalp and identify favorable criteria for their differential diagnosis. METHODS:
We evaluated 15 cases of psoriasis and 20 cases of seborrheic dermatitis of the
scalp that had been clinicopathologically diagnosed. Skin biopsy sections stained
with H&E were examined. Additional immunohistochemistry was performed, including
Ki-67, keratin 10, caspase-5, and GLUT-1. RESULTS: On histopathological
examination, mounds of parakeratosis with neutrophils, spongiform micropustules
of Kogoj, and clubbed and evenly elongated rete ridges were significantly more
frequently observed in psoriasis. Follicular plugging, shoulder parakeratosis and
prominent lymphocytic exocytosis were significantly more common in seborrheic
dermatitis. Moreover, significantly higher mitotic figures were observed in
psoriatic lesions than in seborrheic dermatitis. Immunohistochemistry did not
show any difference between psoriasis and seborrheic dermatitis. CONCLUSION:
Histopathological features favoring psoriasis include mounds of parakeratosis
with neutrophils, spongiform micropustules of Kogoj, clubbed and evenly elongated
rete ridges, and increased mitotic figures (>=6/high-powered field). Features
indicating seborrheic dermatitis are follicular plugging, shoulder parakeratosis
and prominent lymphocytic exocytosis. Immunohistochemistry was not helpful in
differentiating psoriasis from seborrheic dermatitis.
PMID- 27489424
TI - Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in
Calcium-Induced HaCaT Cells.
AB - BACKGROUND: We are continually exposed to low-dose radiation (LDR) in the range
0.1 Gy from natural sources, medical devices, nuclear energy plants, and other
industrial sources of ionizing radiation. There are three models for the
biological mechanism of LDR: the linear no-threshold model, the hormetic model,
and the threshold model. OBJECTIVE: We used keratinocytes as a model system to
investigate the molecular genetic effects of LDR on epidermal cell
differentiation. METHODS: To identify keratinocyte differentiation, we performed
western blots using a specific antibody for involucrin, which is a precursor
protein of the keratinocyte cornified envelope and a marker for keratinocyte
terminal differentiation. We also performed quantitative polymerase chain
reaction. We examined whether LDR induces changes in involucrin messenger RNA
(mRNA) and protein levels in calcium-induced keratinocyte differentiation.
RESULTS: Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a
key regulator that induces growth arrest and represses stemness, which
accelerates keratinocyte differentiation. We correlated involucrin expression
with keratinocyte differentiation, and examined the effects of LDR on involucrin
levels and keratinocyte development. LDR significantly increased involucrin mRNA
and protein levels during calcium-induced keratinocyte differentiation.
CONCLUSION: These studies provide new evidence for the biological role of LDR,
and identify the potential to utilize LDR to regulate or induce keratinocyte
differentiation.
PMID- 27489425
TI - Efficacy of a Complex of 5-Aminolevulinic Acid and Glycyl-Histidyl-Lysine Peptide
on Hair Growth.
AB - BACKGROUND: Pattern hair loss is a very common problem. Although effective
therapeutics for the treatment of pattern hair loss have been used, novel
therapeutic modalities are still required to enhance hair growth. OBJECTIVE: We
investigated the efficacy and safety of a complex (ALAVAX) of 5-aminolevulinic
acid (5-ALA) and glycyl-histidyl-lysine (GHK) peptide for the treatment of
pattern hair loss. METHODS: Forty-five patients with male pattern hair loss were
treated with ALAVAX 100 mg/ml (group A), ALAVAX 50 mg/ml (group B) or placebo
(group C) once a day for 6 months. Total hair count, hair length, hair thickness,
patient's assessment and adverse events were evaluated at month 1, 3, and 6.
RESULTS: An increase in hair count for 6 months was 52.6 (p<0.05) in group A,
71.5 (p<0.05) in group B, and 9.6 in group C. The ratio of changes in hair count
between group B (2.38) and group C (1.21) at 6 months showed a statistically
significant difference (p<0.05). The proportion above good satisfaction was
higher in group A (26.7%) than in the other groups (group B: 14.3%, group C:
7.1%). There was no statistically significant difference in hair length and hair
thickness among 3 groups at 6 months. There was no adverse event in 3 groups.
CONCLUSION: Our study showed that a complex of 5-ALA and GHK peptide may be
considered as one of the complementary agents for the treatment of male pattern
hair loss.
PMID- 27489426
TI - Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in
the Treatment of Androgenetic Alopecia.
AB - BACKGROUND: After the approval of dutastride for androgenic alopecia (AGA) in
2009, Korean authority required a post-marketing surveillance to obtain further
data on its safety profile. OBJECTIVE: The objective was to monitor adverse
events (AEs) of dutasteride 0.5 mg in Korean AGA male patients in a clinical
practice environment. METHODS: Open label, multi-center, non-interventional
observational study was done from July 2009 to July 2013. AGA subjects (18~41
years of age) with no experience of dutasteride were enrolled. Dosage regimen was
recommended according to the prescribing information. The incidences of any AEs,
serious adverse events (SAEs), and adverse drug reactions (ADRs) were evaluated.
Multiple logistic regression method was used to identify risk factors related to
ADRs. Effectiveness was generally evaluated by physicians. RESULTS: During study
period, 712 subjects were enrolled. The subjects of 29.3+/-6.0 years old exposed
to dutasteride for 204.7+/-161.5 days. One hundred and ten (15.4%) of subjects
reported 138 AEs. Four subjects (0.6%) reported 5 SAEs (right radius fracture, 2
events of chronic follicular tonsillitis, influenza infection, and acute
appendicitis). Sixty-six subjects (9.3%) reported 80 ADRs. Most frequent ADRs
were libido decreased (9 subjects, 1.3%), dyspepsia (8 subjects, 1.1%), impotence
(7 subjects, 1.0%), and fatigue (5 subjects, 0.7%). Other interested ADRs were
sexual function abnormality (4 subjects, 0.6%), gynecomastia (2 subjects, 0.3%),
and ejaculation disorder (1 subject, 0.1%). Most subjects (78.6%) showed overall
improvement after treatment of dutasteride in the effectiveness. CONCLUSION:
Dutasteride 0.5 mg is to be well-tolerated in 18 to 41 years old AGA patients in
a clinical practice environment.
PMID- 27489427
TI - Immunohistochemical Comparison of IL-36 and the IL-23/Th17 Axis of Generalized
Pustular Psoriasis and Acute Generalized Exanthematous Pustulosis.
AB - BACKGROUND: Cutaneous pustular disorders include generalized pustular psoriasis
(GPP) and acute generalized exanthematous pustulosis (AGEP). OBJECTIVE: To
identify differences between GPP and AGEP, here we immunohistochemically
evaluated interleukin (IL)-36 and the IL-23/Th17 axis. METHODS: This
retrospective comparative immunohistochemical study was completed using 11
biopsies of 11 cases of GPP and 11 biopsies of 11 cases of AGEP. Through staining
with the anti-IL-36-alpha (IL-36alpha), anti-IL-36 receptor antagonist (IL-36Ra),
anti-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB),
anti-IL-23, anti-IL-17, and anti-IL-8 antibodies, main expression location and
intensity were visualized in the epidermis and dermis. RESULTS: In both diseases,
diffuse IL-36alpha expression was observed in the epidermis. IL-36Ra expression
was observed in the dermal perivascular area as well as in the epidermis. NF
kappaB expression was observed in the epidermis and perivascular dermal area.
Diffuse IL-23 and IL-17 expression was seen in the whole epidermis and the
perivascular dermal area. IL-8 was expressed in the subcorneal pustules and
parakeratotic area. Contrary to other cytokines, IL-23 expression in the
epidermis of patients with GPP was more intense than only that in patients with
AGEP. CONCLUSION: Common pathomechanisms might exist in the development of GPP
and AGEP based on these immunohistochemical results, but further studies are
needed.
PMID- 27489428
TI - Expression of Epidermal c-Kit+ of Vitiligo Lesions Is Related to Responses to
Excimer Laser.
AB - BACKGROUND: The survival and growth of melanocytes are controlled by the binding
of stem cell factor to its cell surface receptor c-kit+ (CD117). We have observed
that c-kit+ melanocytes existed in some lesions of vitiligo, while Melan A+ cells
were absent. OBJECTIVE: To verify possible relation between c-kit+ expression and
treatment response in non-segmental vitiligo lesions. METHODS: Skin biopsies were
done from the center of the 47 lesions from the 47 patients with non-segmental
vitiligo. Expression of c-kit+ and Melan A, and amounts of melanin in the
epidermis were assessed in each lesion, and treatment responses to excimer laser
were evaluated. RESULTS: Thirty-five of the 47 lesions (74.5%) had c-kit+
phenotypes. There was significant difference of c-kit staining value between good
responders in 3 months of excimer laser treatment (average of 24 sessions) and
the others. CONCLUSION: c-Kit expression in vitiliginous epidermis may be related
to better treatment responses to excimer laser.
PMID- 27489429
TI - Stressful Events and Serum Concentration of Substance P in Acne Patients.
AB - BACKGROUND: Psychological stress is an important factor of acne pathogenesis.
Stress related production of hormones, cytokines and neuropeptides may result in
the chronic course and exacerbations of the disease. OBJECTIVE: The aim of the
study was to evaluate the relationship between acne severity, intensity of
emotional stress and serum concentration of substance P (scSP), to compare the
intensity of adversities, psychological stress and scSP in acne patients with
healthy controls and to compare coping techniques for stress. METHODS: The study
consisted of 80 patients. Emotional stress was analyzed with the use of social
readjustment rating scale, whereas the methods of coping with stress were
assessed with the coping inventory for stressful situation questionnaire. The
blood concentration of substance P was analyzed by enzyme-linked immunosorbent
assay method in a group of 40 patients with acne vulgaris and in control
subjects. RESULTS: There was no statistically significant difference between the
severity of acne and the intensity of stress. Acne patients presented a higher
average scSP than the controls. No statistically significant correlation was
observed between the severity of acne and scSP; however, the intensity of stress
correlated with scSP in the control group. The evaluation of methods of coping
with stress showed significantly higher rate for the avoidance-oriented coping
among acne patients. CONCLUSION: The number of stressful events is not a factor
that determines the severity of acne. The course of the disease may depend on
tolerance to stress and methods of coping with stress.
PMID- 27489431
TI - Immunohistochemistry and Polymerase Chain Reaction for Detection Human Papilloma
Virus in Warts: A Comparative Study.
AB - BACKGROUND: Immunohistochemistry and polymerase chain reaction (PCR) are the most
widely used methods for the detection of viruses. PCR is known to be a more
sensitive and specific method than the immunohistochemical method at this time,
but PCR has the disadvantages of high cost and skilled work to use widely. With
the progress of technology, the immunohistochemical methods used in these days
has come to be highly sensitive and actively used in the diagnostic fields.
OBJECTIVE: To evaluate and compare the usefulness of immunohistochemistry and PCR
for detection human papilloma virus (HPV) in wart lesions. METHODS: Nine biopsy
samples of verruca vulgaris and 10 of condyloma accuminatum were examined.
Immunohistochemical staining using monoclonal antibody to HPV L1 capsid protein
and PCR were done for the samples. DNA sequencing of the PCR products and HPV
genotyping were also done. RESULTS: HPV detection rate was 78.9% (88.9% in
verruca vulgaris, 70.0% in condyloma accuminatum) on immunohistochemistry and
100.0% for PCR. HPV-6 genotype showed a lower positivity rate on
immunohistochemistry (50.0%) as compared to that of the other HPV genotypes.
CONCLUSION: Immunohistochemistry for HPV L1 capsid protein showed comparable
sensitivity for detection HPV. Considering the high cost and great effort needed
for the PCR methods, we can use immunohistochemistry for HPV L1 capsid protein
with the advantage of lower cost and simple methods for HPV detection.
PMID- 27489430
TI - Change in Antimicrobial Susceptibility of Skin-Colonizing Staphylococcus aureus
in Korean Patients with Atopic Dermatitis during Ten-Year Period.
AB - BACKGROUND: A small subset of adolescents atopic dermatitis (AD) tends to
persist. This also leads to get more antibiotics exposure with advancing years.
Antibiotic resistance has been regarded as a serious problem during
Staphylococcus aureus treatment, especially methicillin-resistant S. aureus
(MRSA). OBJECTIVE: It was investigated the S. aureus colonization frequency in
the skin lesions and anterior nares of adolescent AD patients and evaluated the
changes in S. aureus antimicrobial susceptibility for years. METHODS: Patients
who visited our clinic from September 2003 to August 2005 were classified into
group A, and patients who visited from August 2010 to March 2012 were classified
into group B. To investigate the differences with regard to patients' age and
disease duration, the patients were subdivided into groups according to age.
Lesional and nasal specimens were examined. RESULTS: Among the 295 AD patients,
the total S. aureus colonization rate in skin lesions was 66.9% (95/142) for
group A and 78.4% (120/153) for group B. No significant changes in the systemic
antimicrobial susceptibilities of S. aureus strains isolated from adolescent AD
patients were observed during about 10-year period. The increased trend of MRSA
isolation in recent adolescent AD outpatients suggest that the community
including school could be the source of S. aureus antibiotic resistance and
higher fusidic acid resistance rates provides evidence of imprudent topical use.
CONCLUSION: Relatively high MRSA isolation and fusidic acid resistance rates in
recent AD patients suggest that the community harbors antibiotic-resistant S.
aureus.
PMID- 27489432
TI - Increased Infiltration of CD8(+) T Cells by Dacarbazine in a Patient with Mucosal
Penile Melanoma Refractory to Nivolumab.
AB - Primary penile melanomas are rare tumors that represent less than 0.1% of all
melanomas. We report a case of a 60-year-old Japanese male with a mucosal penile
melanoma and describe an increased CD8(+) T cell infiltration in brain after
dacarbazine (DTIC) administration. After partial penectomy and left inguinal
lymphadenectomy, he developed multiple lung, bone, spleen, brain and skin
metastases. He was treated with interferon-beta, DTIC and nivolumab. However, the
metastases were not reduced in size. Immunohistochemistry showed an increase of
CD8(+) T cell infiltration and programmed death-ligand 1 (PD-L1) expression after
the administration of DTIC, but the expression of programmed cell death protein 1
(PD-1) was negative. We speculate that DTIC exerted immunostimulatory effects,
but nivolumab was ineffective due to the negative expression of PD-1 and/or an
insufficient infiltration of CD8(+) T cells. Although this is only one case, this
case report could be the first step to discuss the development of effective
therapies against melanoma to take advantage of the increased CD8(+) T cell
infiltration elicited by chemotherapeutic agents. It would be beneficial to pay
more attention to the relationship between DTIC and immune checkpoint modulators.
PMID- 27489433
TI - Synchronous Occurrence of Primary Cutaneous Anaplastic Large Cell Lymphoma and
Squamous Cell Carcinoma.
AB - CD30+ lymphoproliferative disorders (LPD) represent a spectrum of T-cell lymphoma
including lymphomatoid papulosis and anaplastic large cell lymphoma (ALCL).
Epidermis overlying cutaneous CD30+ LPD often shows epidermal hyperplasia,
hyperkeratosis, crusting, and ulceration and it is difficult to distinguish from
carcinoma such as keratoacanthoma (KA) or squamous cell carcinoma (SCC). Several
cases of pseudocarcinomatous hyperplasia mimicking KA or SCC in CD30+ LPD have
been reported. The relationship between CD30+ LPD and epithelial proliferations
has not yet well understood. It was reported that a variety of mediators,
including epidermal growth factor (EGF), transforming growth factor-alpha and
EGFR from CD30+ LPD could attribute to epidermal hyperplasia. However, separate
and distinct SCC occurring in CD30+ LPD has rarely been reported. Herein, we
present a rare case of coexistence of SCC and cutaneous ALCL located on the same
region.
PMID- 27489434
TI - Fibro-Osseous Pseudotumor of the Digit: A Diagnostic Pitfall of Extraskeletal
Osteosarcoma.
PMID- 27489435
TI - Extramammary Paget's Disease Combined with Squamous Cell Carcinoma In Situ of the
Vulva: A Case Report and Differential Diagnosis.
PMID- 27489436
TI - A Unique Cutaneous Presentation of Breast Cancer: A Red Apple Stuck in the
Breast.
PMID- 27489437
TI - Transepidermal Elimination of Gold Metals after Face-Lifting Acupuncture.
PMID- 27489438
TI - Homozygous Deletion Mutation of the FERMT1 Gene in a Chinese Patient with Kindler
Syndrome.
PMID- 27489439
TI - A Case of Facial Sarcoptes scabiei in a Female Child.
PMID- 27489440
TI - Cutaneous Sporotrichosis Presenting as Clinical Feature of Facial Cellulitis in
an Adult.
PMID- 27489441
TI - Scar Sarcoidosis Induced by Pulsed Dye Laser Treatment.
PMID- 27489442
TI - A Case of Late Stage Sebaceous Trichofolliculoma Showing Overlapping Features
with Folliculosebaceous Cystic Hamartoma.
PMID- 27489443
TI - Multiple Acquired Periungual Fibrokeratoma.
PMID- 27489444
TI - Donut Ablation Method as an Alternative to Surgical Excision or Total Ablational
Laser Treatment.
PMID- 27489445
TI - Acral Persistent Papular Mucinosis with Partial Response to Tacrolimus Ointment.
PMID- 27489446
TI - Cutaneous Metastasis of Rhabdomyosarcoma Originated from Maxillary Sinus in a
Young Adult Female.
PMID- 27489447
TI - Palmoplantar Pustulosis Induced by both Adalimumab and Golimumab for Treatment of
Ankylosing Spondylitis.
PMID- 27489448
TI - The Epidemiology of Dermatophyte Infection in Southeastern Korea (1979~2013).
PMID- 27489449
TI - Periungual Abscess Caused by Citrobacter braakii in a Patient with Chronic
Paronychia.
PMID- 27489450
TI - A Rare Cutaneous Adverse Reaction after Intra-Articular Injection of Hyaluronic
Acid.
PMID- 27489451
TI - Digital applications: the future in psychiatry?
AB - Digital applications and new mobile technologies can change the nature of the
psychiatrist-patient relationship and future clinical practice in terms of
diagnosis, follow-up, and treatment, but need to be further studied. This issue
explores these new approaches in psychiatry.
PMID- 27489452
TI - The emerging story of emerging technologies in neuropsychiatry.
AB - The growth of new technologies in health care is exponential, and the impact of
such rapid technological innovation on health care delivery is substantial. This
review describes two emerging technologies-mobile applications and wearable
technologies-and uses a virtual case report to illustrate the impact of currently
available technologies on the health care experience of a patient with
neuropsychiatric illness.
PMID- 27489453
TI - Issues and developments related to assessing function in serious mental illness.
AB - Serious mental illness (SMI) results in functional disability that imposes a
significant burden on individuals, caregivers, and society. Development of novel
treatments is under way in an effort to improve the illness domains of cognitive
impairment and negative symptoms and subsequently to improve functional outcomes.
The assessment of functional outcomes in SMI faces a number of challenges,
including the proliferation of assessment instruments and the differential
prioritization of functional goals among stakeholder groups. Functional
assessments relying on self- and informant report present a number of
limitations. Identifying alternative strategies to assess functioning that are
reliable, valid, and sensitive to change is necessary for use in clinical trials.
Measures of functional capacity have been proposed for clinical trials
investigating compounds to treat cognitive impairment in schizophrenia.
Alternative approaches employing effort-based decision making or daily activity
recording using instruments such as the Daily Activity Report may be more
appropriate for studies focused on improving negative symptoms.
PMID- 27489454
TI - Functional assessment in mental health: lessons from occupational therapy.
AB - Occupational therapists have been conducting functional assessments since World
War I, and this accumulated experience has taught us several critical lessons.
First, a comprehensive profile of a patient's functioning requires multiple
assessment methods. Second, assessment content and measurement constructs must
change with the times. Third, technology can enhance and extend functional
assessment. Fourth, performance-based assessments of everyday activities can also
be used to measure body functions/impairments. However, while deconstructing
activities into body functions/impairments is possible, the results do not
reflect patients' abilities to integrate the cognitive, motor, sensory and
affective functions necessary to complete a complex activity. Finally, the
differential complexity of everyday activities that a patient can master or
successfully complete can also provide a ruler with which to measure progress.
PMID- 27489455
TI - Neurotechnological assessment of consciousness disorders: five ethical
imperatives.
AB - Disorders of consciousness (DOCs) cause great human suffering and material costs
for society. Understanding of these disorders has advanced remarkably in recent
years, but uncertainty remains with respect to the diagnostic criteria and
standards of care. One of the most serious problems concerns misdiagnoses, their
impact on medical decision-making, and on patients' well-being. Recent studies
use neurotechnology to assess residual consciousness in DOC patients that
traditional behavioral diagnostic criteria are unable to detect. The results show
an urgent need to strengthen the development of new diagnostic tools and more
refined diagnostic criteria. If residual consciousness may be inferred from
robust and reproducible results from neurotechnological communication with DOC
patients, this also raises ethical challenges. With reference to the moral
notions of beneficence and fundamental rights, five ethical imperatives are here
suggested in terms of diagnosis, communication, interpretation of subjective
states, adaptation of living conditions, and care.
PMID- 27489456
TI - Mobile technology for mental health assessment.
AB - Assessment and outcome monitoring are critical for the effective detection and
treatment of mental illness. Traditional methods of capturing social, functional,
and behavioral data are limited to the information that patients report back to
their health care provider at selected points in time. As a result, these data
are not accurate accounts of day-to-day functioning, as they are often influenced
by biases in self-report. Mobile technology (mobile applications on smartphones,
activity bracelets) has the potential to overcome such problems with traditional
assessment and provide information about patient symptoms, behavior, and
functioning in real time. Although the use of sensors and apps are widespread,
several questions remain in the field regarding the reliability of off-the-shelf
apps and sensors, use of these tools by consumers, and provider use of these data
in clinical decision-making.
PMID- 27489458
TI - Prevention of suicidal behavior.
AB - More than 800 000 people die every year from suicide, and about 20 times more
attempt suicide. In most countries, suicide risk is highest in older males, and
risk of attempted suicide is highest in younger females. The higher lethal level
of suicidal acts in males is explained by the preference for more lethal methods,
as well as other factors. In the vast majority of cases, suicidal behavior occurs
in the context of psychiatric disorders, depression being the most important one.
Improving the treatment of depression, restricting access to lethal means, and
avoiding the Werther effect (imitation suicide) are central aspects of suicide
prevention programs. In several European regions, the four-level intervention
concept of the European Alliance Against Depression (www.EAAD.net),
simultaneously targeting depression and suicidal behavior, has been found to have
preventive effects on suicidal behavior. It has already been implemented in more
than 100 regions in Europe.
PMID- 27489457
TI - Technology to assess and support self-management in serious mental illness.
AB - The functional impairment associated with serious mental illness (SMI) places an
immense burden on individuals and society, and disability often persists even
after efficacious treatment of psychopathologic symptoms. Traditional methods of
measuring functioning have limitations, and numerous obstacles reduce the reach
and impact of evidence-based interventions developed to improve functioning in
SMI. This review describes the potential of technological innovations for
overcoming the challenges involved in both functional assessment and intervention
in people with SMI. Ecological momentary assessment (EMA), which involves the
repeated sampling of naturalistic behaviors and experiences while individuals
carry out their daily lives, has provided a new window through which the
determinants of day-to-day function in SMI can be observed. EMA has several
advantages over traditional assessment methods and has in recent years evolved to
use mobile-based platforms, such as text messaging and smartphone applications,
for both assessment and promotion of self-management in people with SMI. We will
review promising data regarding the acceptability, adherence, and efficacy of EMA
based mobile technologies; explore ways in which these technologies can extend
the reach and impact of evidence-based psychosocial rehabilitative interventions
in SMI; and outline future directions for research in this important area.
PMID- 27489459
TI - A review of behavioral tailoring strategies for improving medication adherence in
serious mental illness.
AB - Nonadherence to psychopharmacological treatments poses a significant challenge to
treatment success in individuals with serious mental illness, with upwards of 60%
of people not taking their psychiatric medications as prescribed. Nonadherence is
associated with adverse outcomes, including exacerbation of psychiatric symptoms,
impaired functioning, increased hospitalizations and emergency room use, and
increased health care costs. Whereas interventions using psychoeducation or
cognitive approaches, such as motivational interviewing, have largely proven
ineffective in improving adherence, approaches employing behavioral tailoring
that incorporate medication taking into the daily routine and/or use
environmental supports have shown promise. Recently, adherence-enhancing
behavioral tailoring interventions that utilize novel technologies, such as
electronic monitors and mobile phones, have been developed. Although
interventions utilizing these platforms have the potential for widespread
dissemination to a broad range of individuals, most require further empirical
testing. This paper reviews selected behavioral tailoring strategies that aim to
improve medication adherence and other functional outcomes among individuals with
serious mental illness.
PMID- 27489460
TI - Internet interventions for depression: new developments.
AB - A wide range of Internet interventions, mostly grounded in methods of cognitive
behavioral therapy, have been developed and tested for several mental disorders.
The evidence to date shows that these interventions are effective in reducing
symptoms of depression. Metaanalyses report small-to-medium effect sizes when
Internet interventions are delivered as stand-alone self-help interventions
(d=0.25-0.36), and medium-to-large effect sizes when delivered as therapist
guided interventions (d=0.58-0.78), both compared with usual care. Only a
minority of people suffering from depression receive adequate treatment, and
Internet interventions might help bridge the large treatment gap. This review
summarizes the current body of evidence and highlights pros and cons of Internet
interventions. It also outlines how they could be implemented in mental health
care systems and points out unresolved questions, as well as future directions,
in this research field.
PMID- 27489461
TI - Contributions of mobile technologies to addiction research.
AB - Mobile technologies are revolutionizing the field of mental health, and
particular progress has been made in their application to addiction research and
treatment. The use of smartphones and other mobile devices has been shown to be
feasible with individuals addicted to any of a wide range of substances, with few
biases being observed concerning the repeated monitoring of daily life
experiences, craving, or substance use. From a methodological point of view, the
use of mobile technologies overcomes longstanding limitations of traditional
clinical research protocols, including the more accurate assessment of temporal
relationships among variables, as well as the reduction in both contextual
constraints and discipline-specific methodological isolation. The present article
presents a conceptual review of these advances while using illustrations of
research applications that are capable of overcoming specific methodological
barriers. Finally, a brief review of both the benefits and risks of mobile
technology use for the treatment of patients will be addressed.
PMID- 27489462
TI - Influenza and the use of oseltamivir in children.
AB - Influenza is an infectious disease which causes significant morbidity and
mortality. In the USA, approximately 200 000 hospital admissions and 36 000
deaths occur annualy due to severe influenza infections. Although influenza often
causes a simple respiratory infection, it sometimes causes disorders affecting
several organs including the lung, heart, brain, liver and muscles or serious
life-threatening primary viral or secondary bacterial pneumonia. Currently,
oseltamivir is the most important and effective drug for severe influenza
infections. Severe influenza infections can be controlled and related deaths may
be prevented with initiation of this drug especially within first 2 days.
Oseltamivir is usually well tolerated and its most commonly reported side effect
is related with the gastrointestinal system. In conclusion, the course of
influenza changes in a positive direction and the rates of complications and
mortality significantly reduce in patients in whom oseltamivir treatment is
initiated as soon as possible.
PMID- 27489463
TI - The protective effect of pomegranate juice in paracetamol-induced acute
hepatotoxicity in rats.
AB - AIM: Being the most commonly used antipyretic and analgesic, paracetamol is one
of the most common causes of childhood poisoning in the world and maintains its
importance also in our country. Paracetamol poisoning is one of the most common
causes of liver failure. This study aimed to investigate if pomegranate juice had
protective effect in acute liver toxicity related with paracetamol. MATERIAL AND
METHODS: A total of 36 Wistar-Albino rats were divided into four groups as the
paracetamol group (3 000 mg/kg paracetamol), the pomegranate juice + paracetamol
group (1.5 mL pomegranate juice plus 3 000 mg/kg paracetamol), the pomegranate
juice group (1.5 mL pomegranate juice) and the control group (1.5 mL distilled
water). Pomegranate juice and distilled water were administered for eight days.
Paracetamol was administered on day 8. The level of thiobarbituric acid reactive
substances, as an oxidative marker, was measured in the blood and liver tissue on
day 9. In addition, liver tissues were evaluated histologically (in terms of
increased connective tissue, granular degeneration, mononuclear cell
infiltration, necrotic cells and vascular congestion). RESULTS: The liver tissue
and blood thiobarbituric acid reactive substances levels were found to be
significantly lower in the pomegranate juice + paracetamol group compared to the
paracetamol group (p<0.05). Histologically, structural changes related with
damage were observed in both the paracetamol group and pomegranate juice +
paracetamol group. The extent of damage was statistically significantly lower in
the pomegranate juice + paracetamol group (p<0.001). CONCLUSIONS: Our results
related with oxidative and histologic evaluation showed that pomegranate juice
might have a preventive effect in paracetamol-induced acute liver damage.
PMID- 27489464
TI - Febrile neutropenia in children with acute lymphoblastic leukemia: single center
experience.
AB - AIM: An important life-threatening complication of intensive chemotherapy
administered in children with leukemia is febrile neutropenia. The objective of
this study was to evaluate the clinical features and consequences of febrile
neutropenia attacks in children who were treated for acute lymphoblastic
leukemia. MATERIAL AND METHODS: Nighty-six children who received chemotherapy for
acute lymphoblastic leukemia in our center between January 1995 and December 2010
were included in the study. The data related to demographic characteristics,
treatment features, relapse and febrile neutropenia incidences, risk factors,
culture results and prognosis were retrospectively evaluated from the patients'
files. RESULTS: A total of two hundred-ninety nine febrile neutropenia attacks
observed in the patients during initial treatment and relapse treatment were
evaluated. When the incidence of febrile neutropenia was evaluated by years, it
was observed that the patients treated after year 2000 had statistically
significantly more febrile neutopenia attacks compared to the patients treated
before year 2000. When the incidences of febrile neutropenia during initial
treatment and during relapse treatment were compared, it was observed that more
febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent
of all febrile neutropenia attacks were fever of unknown origin. Eighty
microorganisms grew in cultures during febrile neutropenia throughout treatment
in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram
negative), 8% were viral infections and 6% were fungal infections. Coagulase
negative staphylococcus (n=17) was the most frequent gram positive pathogen; E.
Coli (n=17) was the most commonly grown gram negative pathogen. CONCLUSIONS: In
this study, it was found that an increase in the incidence of febrile neutropenia
occured in years. Increments in treatment intensities increase the incidence of
febrile neutropenia while improving survival. Evaluation of febrile neutropenia
results by hematology-oncology units in years will be directive in early and
successful treatment.
PMID- 27489465
TI - Evaluation of cases with cerebral thrombosis in children.
AB - AIM: We aimed to evaluate the patients who were followed up in our clinic with a
diagnosis of cerebral sinovenous thrombosis in terms of age, sex, clinical
findings, etiology, thrombophilic factors, imaging findings, treatment and
prognosis. MATERIAL AND METHODS: The files of 11 patients who were followed up in
our pediatric neurology clinic with a diagnosis of cerebral thrombosis between 1
December 2010 and 31 December 2014 were retrospectively analyzed. RESULTS: Seven
of 11 patients were male (63.6%). The median age was 14 years (2-17 years). Six
(54%) of the patients presented with a complaint of headache. Other complaints at
presentation included diplopia (n:3), weakness and difficulty in speaking (n:1)
and seizure (n:1). A diagnosis of pseudotumor cerebri was made in eight of the
patients (72.7%). In the etiology, mastoiditis was found in three patients,
mastoiditis and meningitis were found in combination in one patient, Behcet's
disease was found in three patients and head trauma was found in one patient. In
3 patients, only prothrombotic genetic risk factors were present; one patient had
deficiency of protein C and S, one patient had deficiency of antithrombin III and
one patient had hyperhomosisteinemia in association with vitamin B12 deficiency.
1A homozygous MTFHR A1298C mutation was detected in the patient who had
mastoiditis and meningitis and protein S deficiency and lupus anticoagulant were
found in another patient who had mastoiditis. All patients received anticoagulant
treatment and all patients recovered without neurological sequelae except one.
CONCLUSIONS: Cerebral sinovenous thrombosis should be considered in patients who
present with headache and focal neurological deficits. Appropriate utilization of
imaging studies is necessary for the diagnosis. Detailed ear, nose and throat
examination should be performed to detect mastoiditis. It is recommended that
genetic risk factors should be investigated, because hereditary thrombophilis
factors may have a role in children. Behcet's disease which is relatively common
in our country should be considered in differential diagnosis.
PMID- 27489466
TI - The effect of vitamin D on lower respiratory tract infections in children.
AB - AIM: Lower respiratory tract infections including mainly pneumonia represent an
important public health problem leading to high mortality and mobidity rates in
children aged below five years in developing countries including our country.
Vitamin D deficiency has been associated with increased risk of
rickets/osteomalacia, various cancers, autoimmune diseases, hyperproliferative
skin diseases, cardiovascular system diseases and infectious diseases. Vitamin D
has an important role in cellular and humoral immunity and pulmonary functions.
Vitamin D deficiency and lower respiratory tract infection are common health
problems in children in our country and no clinical study investigating the
relationship between these problems has been conducted so far. In this case
control study, we aimed to assess the association between vitamin D level and
lower respiratory tract infection in children. MATERIAL AND METHODS: Sixty-three
children aged between six months and five years with lower respiratory infections
and 59 age-matched children who had no history of respiratory symptoms in the
last month and no accompanying chronic disease were compared in terms of vitamin
D levels. The children in the patient group were also evaluated by the clinical
picture. RESULTS: No significant correlation was found between vitamin D levels
and lower respiratory tract infection in terms of disease and its severity.
However, it was found that vitamin D deficiency/ insufficiency was observed with
a high rate in all children included in the study. CONCLUSIONS: Although no
correlation was found between vitamin D level and lower respiratory tract
infection, it is recommended that vitamin D level should be measured in children
with lower respiratory tract infection and vitamin D supplementation should be
given to all children especially in winter months based on the fact that the
level of vitamin D was lower than normal in approximately half of the children
included in the study and considering the effects of vitamin D on infections,
pulmonary functions and immunity.
PMID- 27489467
TI - Celiac disease in children and adolescents with Hashimoto Thyroiditis.
AB - AIM: The aim of this study was to evaluate clinical and laboratory findings and
determine the prevalence of celiac disease (CD) in children with Hashimoto
thyroiditis (HT). MATERIAL AND METHODS: The data of a total of 80 patients with
positive anti-thyroid antibodies who were aged between 6 and 17.9 years were
retrospectively studied. Age, gender, complaints at the time of presentation,
family history of thyroid disorders, clinical and laboratory findings were
recorded. The levels of thyrotropin, free thyroxin, thyroid autoantibodies
(thyroid peroxidase and thyroglobulin antibodies), immunoglobulin A (IgA), anti
tissue transglutaminase antibodies (IgA-tTG), and thyroid ultrasonography
findings were enrolled. RESULTS: Eighty patients (65 females (81.2%) and 15 males
(18,8%)) were included in the study. Family history of thyroid disease was
present in 38 (47.5%) patients. The most common complaints at the time of
presentation were goiter (%30) and weight gain (%25). Forty three (53.8%), 23
(28.7%), and 14 (17.5%) patients presented with euthyroidism, subclinical
hypothyroidism and obvious hypothyroidism. Thirty seven (46.2%) patients had
goiter. IgA-tTG was found to be positive after a diagnosis of HT was made in only
one patient (1.25%) and the diagnosis of CD was confirmed when intestinal biopsy
of this patient revealed villus atrophy, crypt hyperplasia and increase in the
intraepithelial lymphocyte count. CONCLUSIONS: In our study, it was found that
the most common complaints at presentation in patients with a diagnosis of
hashimoto thyroiditis included goiter, weakness and weight gain and the
prevalence of celiac diseases was found to be 1.25% (1/80). This study shows that
the prevalence of CD in patients with a diagnosis of HT is higher compared to the
prevalence in the healthy pediatric population.
PMID- 27489468
TI - A rare sex chromosome aneuploidy: 48,XXYY syndrome.
AB - 48,XXYY syndrome is a rare sex chromosome abnormality. Although some physical
features are similar to Klinefelter syndrome(47,XXY), 48,XXYY is typically
associated with different neuropsyhciatric symptoms and phenotypic findings.
Approximately 100 cases with 48,XXYY have been reported to date. In this report,
a patient who was diagnosed with 48,XXYY syndrome with clincal evaluation and
cytogenetic analysis is presented. A 6-year old male patient was hospitalized due
to recurrent respiratory tract infections, recurrent abdominal distention and
dyspepsia. He was the first and only child of nonconsanguineous parents. He had a
history of mild developmental retardation. In his history, it was learned that he
received treatment for gastroesophageal reflux and his symptoms improved with
treatment. On physical examination, his weight was found to be 31 kg (>97
centile) and his height was found to be 123 cm (90 centile). He had upslanted
palpebral fissures, depressed nasal bridge, long philtrum, incomplete cleft lip
and micrognathia. Clinodactilia was found in the fifth fingers in both hands and
large big toes and adduction in the second and third toes were found in both
feet. Karyotype analysis showed a chromosomal composition of 48,XXYY. The patient
presented here is the second Turkish case of 48,XXYY syndrome.
PMID- 27489469
TI - Sadfly fever: two case reports.
AB - Sandfly fever, also known as 'three-day fever' or 'pappataci fever' or
'Phlebotomus fever' is a viral infection that causes self-limited influenza-like
symptoms and characterized by a rapid onset. The disease occurs commonly in
endemic areas in summer months and especially in August during which sandflies
are active. In this article, two siblings who presented with high fever, redness
in the eyes, headache, weakness, malaise and inability to walk, who were found to
have increased liver function tests and creatine kinase levels and who were
diagnosed with sadfly fever with positive sadfly IgM and IgG antibodies are
reported because of the rarity of this disease.
PMID- 27489470
TI - Withdrawal syndrome and hypomagnesaemia and in a newborn exposed to valproic acid
and carbamazepine during pregnancy.
AB - The usage of drugs during pregnancy affect the fetus and the newborn. In this
report, we present findings from a newborn baby, whose mother was epileptic, and
was under the treatment of valproic acid and carbamazepine during pregnancy. We
have found symptoms of withdrawal syndrome, hyponatremia and feeding problem,
which was most probably related to exposure to the mentioned drugs. We have also
diagnosed hypomagnesaemia and atrial septal defect 4 milimeters in diameter.
There are already many reports about the side effects of valproic acid and
carbamazepine usage during pregnancy. To the best of our knowledge,
hypomagnesaemia has not yet been reported as a side effect. We think that
hypomagnesaemia is also related to the usage of antiepileptics.
PMID- 27489471
TI - Five-year-old girl with tongue bleeding.
PMID- 27489472
TI - Difficulties in the treatment of an Infant with Hemophilia B.
PMID- 27489473
TI - A new species of Dianthus (Caryophyllaceae) from Antalya, South Anatolia, Turkey.
AB - Dianthus multiflorus from Gazipasa (Antalya), south Anatolia (Turkey), is
described as a new annual species with verrucose calyx. The morphological
differences from the species within the same group with Dianthus multiflorus,
which are Dianthus aydogdui, Dianthus cyri and Dianthus tripunctatus, are
discussed. The International Union for Conservation of Nature (IUCN) threat
category and observations on the ecology of the populations are noted. The
karyology and seed micromorphology of Dianthus multiflorus and Dianthus
tripunctatus were examined by light microscopy and scanning electron microscopy.
PMID- 27489474
TI - Typification of names of South American taxa related to Woodsia montevidensis
(Woodsiaceae).
AB - A revision of the nomenclature of six South American taxa related to Woodsia is
presented, as a part of a taxonomic revision of the genus in South America.
Lectotypes are selected for Cheilanthes crenata, Woodsia crenata var. pallidipes,
Woodsia incisa, Woodsia montevidensis var. fuscipes and the second step
lectotypification for Dicksonia montevidensis and Woodsia peruviana, based on the
analysis of their protologues and original herbarium material. All names are
currently synonyms of Woodsia montevidensis. Physematium incisum (Gillies ex
Hook. & Grev.) Kunze constitutes an illegitimate name and Physematium cumingianum
is considered as nomen inquirendum.
PMID- 27489475
TI - New functionally dioecious bush tomato from northwestern Australia, Solanum
ossicruentum, may utilize "trample burr" dispersal.
AB - A new Australian species of functionally dioecious bush tomato of Solanum
subgenus Leptostemonum is described. Solanum ossicruentum Martine & J.Cantley,
sp. nov., is thought to be allied with members of the problematic "Dioicum
Complex" lineage, but differs in its short silvery indumentum, long calyx lobes,
larger stature, and an unusual fruit morphology that may represent "trample burr"
seed dispersal. The species occurs in a range extending from the eastern
Kimberley in Western Australia to far northwestern Northern Territory and has
been recognized for decades as a variant of Solanum dioicum W.Fitzg. Specimens of
this species were previously referred to by D.E. Symon and others as Solanum
dioicum 'Tanami.' Ex situ crossing studies and SEM images of inaperturate pollen
grains produced in morphologically hermaphrodite flowers indicate that this taxon
is functionally dioecious. The scientific name was chosen with the help of 150
seventh grade life science students from Pennsylvania, USA.
PMID- 27489476
TI - Miconia papillosperma (Melastomataceae, Miconieae): a new species from Amazonas,
Brazil.
AB - Miconia papillosperma, a new species of Melastomataceae shrubs from Northern
Brazil is described and illustrated. This new species is characterized by
elliptic lanceolate leaves with the only pair of secondary veins running close to
the margin. It is also unique in having seeds with a papillose testa, a character
until now unknown in the Miconieae. The description of this new species from a
relatively well collected area near a major road north of Manaus, Amazonas,
Brazil, is further evidence of our lack of knowledge on plants in many
Neotropical areas.
PMID- 27489477
TI - Spiradiclis pengshuiensis (Ophiorrhizeae, Rubioideae), a new species from
Chongqing, China.
AB - Spiradiclis pengshuiensis Bo Pan & R. J. Wang (Rubiaceae) is described as a new
species from Chongqing in SW China. It is morphologically compared with
Spiradiclis pauciflora L. Wu & Q. R. Liu because of their similarities in habit,
pubescent surface, small leaf laminas and subglobose capsules. Its conservation
status is evaluated as "VU" according to the IUCN categories and criteria.
PMID- 27489479
TI - A new species in the tree genus Polyceratocarpus (Annonaceae) from the Udzungwa
Mountains of Tanzania.
AB - Polyceratocarpus askhambryan-iringae, an endemic tree species of Annonaceae from
the Udzungwa Mountains of Tanzania, is described and illustrated. The new species
is identified as a member of the genus Polyceratocarpus by the combination of
staminate and bisexual flowers, axillary inflorescences, subequal outer and inner
petals, and multi-seeded monocarps with pitted seeds. From Polyceratocarpus
scheffleri, with which it has previously been confused, it differs in the longer
pedicels, smaller and thinner petals, shorter bracts, and by generally smaller,
less curved monocarps that have a clear stipe and usually have fewer seeds.
Because Polyceratocarpus askhambryan-iringae has a restricted extent of
occurrence, area of occupancy, and ongoing degradation of its forest habitat, we
recommend classification of it as Endangered (EN) on the IUCN Red List.
PMID- 27489478
TI - Molecular and morphological evidence for Penstemon luculentus (Plantaginaceae): a
replacement name for Penstemon fremontii var. glabrescens.
AB - Penstemon luculentus R.L.Johnson & M.R.Stevens, nom. nov. replaces Penstemon
fremontii var. glabrescens Dorn & Lichvar. The varietal name glabrescens was not
elevated because it was already occupied by Penstemon glabrescens Pennell, a
different species. This new arrangement is supported by molecular and
morphological evidence. An analysis of genetic diversity in populations of both
varieties of Penstemon fremontii Torr. & A. Gray (glabrescens and fremontii) from
the Piceance Basin, Colorado, using SSR (simple sequences repeats) or
microsatellites markers, revealed significant genetic differentiation between the
two. Penstemon fremontii var. glabrescens was also genetically different from
Penstemon gibbensii Dorn and Penstemon scariosus var. garrettii (Pennell) N.H.
Holmgren. The combination of hirtellous stems, glabrous leaves, non-glandular
inflorescence, and long anther hairs distinguish Penstemon luculentus from other
morphologically similar species.
PMID- 27489480
TI - New combinations in Odontostemma (Caryophyllaceae).
AB - Sixty-three new combinations in Odontostemma (Alsineae, Caryophyllaceae) are made
to accommodate placement of all currently recognized taxa of Arenaria subg.
Odontostemma within the genus Odontostemma.
PMID- 27489481
TI - A new species of Clinanthus from northern Peru (Asparagales, Amaryllidaceae,
Amarylloideae, Clinantheae).
AB - Clinanthus milagroanthus S. Leiva & Meerow, sp. nov. is described from the
Department of La Libertad in Peru. The new species is most closely related to
Clinanthus mirabilis (Ravenna) Meerow, with further affinities to Clinanthus
viridiflorus (R. & P.) Meerow. It can be distinguished from Clinanthus mirabilis
by its wider leaves, the much more brightly colored and wide spreading limb, and
the much lighter colored perigone tube (yellowish green vs. dark green in
Clinanthus mirabilis). A conspicuous bulge just proximal to the midpoint of the
tube is a unique character of the new species.
PMID- 27489482
TI - A revision of Poa subsection Aphanelytrum (Poaceae, Pooideae, Poaeae, Poinae);
and a new species, Poa auriculata.
AB - In this study the peculiar Andean grass genus Aphanelytrum, with two species, is
reduced to Poa subsect. Aphanelytrum comb. & stat. nov. A third species, Festuca
reclinata, is assigned to the subsection, which shows states transitional between
a more typical Poa and Aphanelytrum. Poa subgen. Poa supersect. Homalopoa sect.
Dioicopoa subsect. Aphanelytrum comb. & stat. nov. is characterized in having
stooling perennials with decumbent to spreading culm bases that continuously
branch and often root at low to mid-culm nodes, glabrous spikelets with long
rachillas 1.2-4.2 mm long, short glumes less than 1/2 the length of the florets,
and lemmas with bifid apexes that are mucronate to short-awned. We provide for
the three species taxonomic discussions, morphological and anatomical
descriptions, keys, illustrations, and a list of specimens. Also, we provide two
new names, Poa hitchcockiana nom. nov. and Poa sanchez-vegae nom. nov., and one
new combination, Poa reclinata comb. nov. A new species, Poa auriculata sp. nov.
from Peru, not thought to be a member of Poa subsect. Aphanelytrum, is presented.
It is the first in the genus with prominent auricles. In addition, we place Poa
apiculata in Poa subgen. Poa supersect. Homalopoa sect. Dioicopoa subsect.
Tovarochloa comb. & stat. nov.
PMID- 27489483
TI - The Andean Paepalanthus pilosus complex (Eriocaulaceae): a revision with three
new taxa.
AB - A herbarium-based revision is provided for Paepalanthus pilosus and allies, five
commonly confused species of cushion plants native to Andean paramo. These are
placed in the recircumscribed Paepalanthus subsect. Cryptanthella Suess. The
group includes Paepalanthus pilosus, Paepalanthus dendroides, and Paepalanthus
lodiculoides. An additional two species and one variety are newly described:
Paepalanthus caryonauta, Paepalanthus huancabambensis, and Paepalanthus pilosus
var. leoniae. The latter two are Peruvian endemics, while Paepalanthus caryonauta
is known from four countries, and has long been confused with other species. An
additional, possibly undescribed taxon is noted from the Serrania de Perija,
Colombia. Five new synonyms and three lectotypes are proposed, and the common
misapplication of some names is noted. Within the Paepalanthus pilosus complex,
species differences were found in timing of peduncle elongation, sex ratio, and
leaf, perianth, diaspore and nectary morphology. Ecological differences are
suggested by specimen data and a review of ecological literature. Descriptions,
photographs and maps are provided for all species, as is a key to the groups of
eriocaulaceous cushion plants from Andean South America.
PMID- 27489484
TI - A brief botanical survey into Kumbira forest, an isolated patch of Guineo
Congolian biome.
AB - Kumbira forest is a discrete patch of moist forest of Guineo-Congolian biome in
Western Angola central scarp and runs through Cuanza Norte and Cuanza Sul
province. The project aimed to document the floristic diversity of the Angolan
escarpment, a combination of general walk-over survey, plant specimen collection
and sight observation was used to aid the characterization of the vegetation.
Over 100 plant specimens in flower or fruit were collected within four identified
vegetation types. The list of species includes two new records of Guineo
Congolian species in Angola, one new record for the country and one potential new
species.
PMID- 27489485
TI - A new species of Amphitecna (Bignoniaceae) endemic to Chiapas, Mexico.
AB - Amphitecna loreae Ortiz-Rodr. & Burelo, sp. nov. (Bignoniaceae), a new species
endemic to the karst rainforest in southern Mexico, is described and illustrated.
The new species differs from the other species of Amphitecna by the combination
of cauliflorous inflorescences, larger flowers, buds rounded at apex, and globose
ellipsoid rather than acuminate fruits. A key to the Mexican species of
Amphitecna is presented.
PMID- 27489486
TI - Cephalaria anamurensis (Caprifoliaceae), a new species from south Anatolia,
Turkey.
AB - A new species, Cephalaria anamurensis (Caprifoliaceae) is described and
illustrated from south Anatolia, Turkey. The species grows on steppe and stony
places in Anamur (C4 Mersin province) in south Anatolia. Diagnostic morphological
characters from closely similar taxa are discussed. The geographical distribution
of the new species and two closely related species in Turkey are mapped.
PMID- 27489487
TI - Flora of Bokor National Park V: Two new species of Machilus (Lauraceae), M.
bokorensis and M. brevipaniculata.
AB - Two new species, Machilus bokorensis Yahara & Tagane and Machilus brevipaniculata
Yahara & Tagane (Lauraceae) are described from Bokor National Park, Cambodia with
their illustrations and DNA barcodes of the two plastid regions of rbcL and matK
and the nuclear region of ITS.
PMID- 27489488
TI - A new species of Eustigma (Hamamelidaceae) from Hon Ba Nature Reserve, Vietnam.
AB - A new species of Hamamelidaceae, Eustigma honbaense H.Toyama, Tagane & V.S.Dang,
sp. nov., is described from Hon Ba Nature Reserve, Vietnam. This species is
similar to Eustigma oblongifolium Gardner & Champ., but differs from it in having
entire leaves, longer infructescences, capsules with a longer apical part and
seeds with a larger hilum. A description, preliminary conservation assessment,
illustration and photographs of the new species are provided, as well as an
updated key to the genus Eustigma.
PMID- 27489489
TI - An updated checklist and key to the open-panicled species of Poa L. (Poaceae) in
Peru including three new species, Poa ramoniana, Poa tayacajaensis, and Poa
urubambensis.
AB - We provide an updated checklist and key to the 30 Poa species with open panicles
from Peru which includes previously circumscribed Dissanthelium and Aphanelytrum
species, new taxon records, and three undescribed species. Poa compressa, Poa
grisebachii, and Poa leioclada are recorded from Peru for the first time. A
number of species are placed in synonymy: Poa carazensis, Poa ferreyrae and Poa
tovarii are synonymized under the name Poa fibrifera; Poa adusta (tentatively)
and Poa pilgeri are synonymized under Poa candamoana; Poa superata is synonymized
under Poa grisebachii; and Poa paramoensis is synonymized under Poa
huancavelicae. Included within this treatment are three new species, Poa
ramoniana, Poa tayacajaensis and Poa urubambensis, which are described and
illustrated. Poa ramoniana, found growing near lakes in high elevation Puna
grasslands of Junin, is similar to a small form of Poa glaberrima, but differs in
having rhizomes and growing to only 5 cm tall. Poa tayacajaensis, found from
shrublands on Andean slopes of Huancavelica and Huanuco, bears similarities to
Poa aequatoriensis but differs in having shorter lemmas which are pubescent
between the veins, densely scabrous sheaths with smooth, glabrous throats, and
shorter ligules. Poa urubambensis, a common element of the undisturbed Polylepis
forest understory of the Cordillera Urubamba, Cusco, is distinct from all other
members of open-panicled Poa's by having glabrous lemmas with a smooth and
glabrous callus, and notably small anthers. The type material for the name Poa
adusta is discussed and a lectotype is selected.
PMID- 27489490
TI - Typifications and synonymy in Polystichum (Dryopteridaceae) from Chile and
Argentina.
AB - Polystichum Roth is one of the largest and most taxonomically challenging fern
genera. South American species have a rich and complex nomenclatural history;
many of the early names are inadequately typified. Based on extensive examination
of original type material, we designate eleven lectotypes (including Aspidium
mohrioides, Aspidium montevidense f. imbricata, Aspidium montevidense f.
squamulosa, Aspidium plicatum, Aspidium pycnolepis, Dicksonia andina, Polystichum
elegans, Polystichum mohrioides f. latifolia, Polystichum multifidum var.
autranii, Polystichum platyphyllum var. kurtziana, and Polypodium
polystichoides), and one neotype (Polystichum brongniartianum) for Polystichum
taxa. Furthermore, three new synonyms are proposed.
PMID- 27489491
TI - Bulbophyllum pingnanense (Orchidaceae, Epidendroideae, Dendrobiinae), a new
species from Fujian, China.
AB - A new orchid species, Bulbophyllum pingnanense, is described and illustrated from
Fujian, China. It is similar to Bulbophyllum brevipedunculatum and Bulbophyllum
albociliatum in vegetative and floral morphology, but it can be distinguished
from Bulbophyllum brevipedunculatum by having a longer dorsal sepal with longer
white ciliate on margin, longer and lanceolate lateral sepals, and a glabrous
lip. It can be distinguished from Bulbophyllum albociliatum by having a shorter
inflorescence, and a longer dorsal sepal.
PMID- 27489492
TI - Telipogon diabolicus (Orchidaceae, Oncidiinae), a new species from southern
Colombia.
AB - A new species of the orchid genus Telipogon, Telipogon diabolicus, is described
and illustrated. The information about its habitat is provided. The novelty
resembles Telipogon tabanensis and Telipogon guacamayensis and it is
characterized by the translucent flowers, the glabrous, distinctly clawed petals,
the transversely elliptic lip, and the gynostemium ornamented with long setose
hairs on both sides and shorter hairs at the apex.
PMID- 27489493
TI - Popowia bachmaensis (Annonaceae), a new species from Bach Ma National Park,
Central Vietnam.
AB - A new species, Popowia bachmaensis Ngoc, Tagane & Yahara, sp. nov. is described
from Bach Ma National Park in Thua Thien Hue Province, Central Vietnam. This
species is morphologically similar to Popowia pisocarpa (Blume) Endl. ex Walp.,
but can be readily distinguished from it by its lower stems, smaller leaves,
shorter flowering pedicels, shorter carpels, longer sepals and inner petals. A
detailed description, comprising illustrations, and supplemented with DNA
barcodes of the two regions of rbcL and matK, are provided.
PMID- 27489494
TI - A revision of the "African Non-Spiny" Clade of Solanum L. (Solanum sections
Afrosolanum Bitter, Benderianum Bitter, Lemurisolanum Bitter, Lyciosolanum
Bitter, Macronesiotes Bitter, and Quadrangulare Bitter: Solanaceae).
AB - The African Non-Spiny (ANS) clade contains 14 species of mostly large canopy
lianas or scandent shrubs confined to Madagascar (10) and continental Africa (4,
with with one species reaching the southern Arabian peninsula). Members of the
clade were previously classified in sections Afrosolanum Bitter, Benderianum
Bitter, Lemurisolanum Bitter, Macronesiotes Bitter and Quadrangulare Bitter, and
were throught to be related to a variety of New World groups. The group is an
early-branching lineage of non-spiny solanums and characters shared with other
vining New World solanums are homoplastic. The 14 species of the group occupy a
wide range of habitats, from wet forests in western Africa to savanna and dry
forests of southern Madagascar and dune habitats in South Africa. Many members of
the group are highly variable morphologically, and habit can vary between shrub
and canopy vine in a single locality. We here review the taxonomic history,
morphology, potential relationships and ecology of these species; we provide keys
for their identification, descriptions, full synonymy (including designations of
lectotypes and neotypes) and nomenclatural notes. Illustrations, distribution
maps and preliminary conservation assessments are provided for all species.
PMID- 27489495
TI - Generation of a Mouse Full-length Balancer with Versatile Cassette-shuttling
Selection Strategy.
AB - Balancer chromosomes are important tools for a variety of genetic manipulations
in lower model organisms, owing to their ability to suppress recombination. In
mouse, however, such effort has not been accomplished, mostly due to the size of
the chromosomes and the complexity of multiple step chromosomal engineering. We
developed an effective and versatile cassette-shuttling selection (CASS) strategy
involving only two selection markers to achieve the sequential production of
multiple large inversions along the chromosome. Using this strategy, we
successfully generated the first full-length balancer in mice and showed that
Balancer 17M-GFP can efficiently suppress recombination. Our study has not only
generated a useful genetic resource, but also provided a strategy for
constructing mammalian balancer chromosomes.
PMID- 27489496
TI - Yorkie Facilitates Organ Growth and Metamorphosis in Bombyx.
AB - The Hippo pathway, which was identified from genetic screens in the fruit fly,
Drosophila melanogaster, has a major size-control function in animals. All key
components of the Hippo pathway, including the transcriptional coactivator Yorkie
that is the most critical substrate and downstream effector of the Hippo kinase
cassette, are found in the silkworm, Bombyx mori. As revealed by microarray and
quantitative real-time PCR, expression of Hippo pathway genes is particularly
enriched in several mitotic tissues, including the ovary, testis, and wing disc.
Developmental profiles of Hippo pathway genes are generally similar (with the
exception of Yorkie) within each organ, but vary greatly in different tissues
showing nearly opposing expression patterns in the wing disc and the posterior
silk gland (PSG) on day 2 of the prepupal stage. Importantly, the reduction of
Yorkie expression by RNAi downregulated Yorkie target genes in the ovary,
decreased egg number, and delayed larval-pupal-adult metamorphosis. In contrast,
baculovirus-mediated Yorkie(CA) overexpression upregulated Yorkie target genes in
the PSG, increased PSG size, and accelerated larval-pupal metamorphosis. Together
the results show that Yorkie potentially facilitates organ growth and
metamorphosis, and suggest that the evolutionarily conserved Hippo pathway is
critical for size control, particularly for PSG growth, in the silkworm.
PMID- 27489497
TI - The Protein Elicitor PevD1 Enhances Resistance to Pathogens and Promotes Growth
in Arabidopsis.
AB - The protein elicitor PevD1, isolated from Verticillium dahlia, could enhance
resistance to TMV in tobacco and Verticillium wilt in cotton. Here, the pevd1
gene was over-expressed in wild type (WT) Arabidopsis, and its biological
functions were investigated. Our results showed that the transgenic lines were
more resistant to Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000
than the WT line was. In transgenic plants, both the germination time and bolting
time required were significantly shorter and fresh weights and plant heights were
significantly higher than those in the WT line. A transcriptomics study using
digital gene expression profiling (DGE) was performed in transgenic and WT
Arabidopsis. One hundred and thirty-six differentially expressed genes were
identified. In transgenic Arabidopsis, three critical regulators of JA
biosynthesis were up-regulated and JA levels were slightly increased. Three
important repressors of the ABA-responsive pathway were up-regulated, indicating
that ABA signal transduction may be suppressed. One CML and two WRKY TFs involved
in Ca(2+)-responsive pathways were up-regulated, indicating that this pathway may
have been triggered. In conclusion, we show that PevD1 is involved in regulating
several plant endogenous signal transduction pathways and regulatory networks to
enhance resistance and promote growth and development in Arabidopsis.
PMID- 27489498
TI - Protective Effect of Thymoquinone against Cyclophosphamide-Induced Hemorrhagic
Cystitis through Inhibiting DNA Damage and Upregulation of Nrf2 Expression.
AB - Cyclophosphamide (CYP) induced hemorrhagic cystitis is a dose-limiting side
effect involving increased oxidative stress, inflammatory cytokines and
suppressed activity of nuclear factor related erythroid 2-related factor (Nrf2).
Thymoquinone (TQ), an active constituent of Nigella sativa seeds, is reported to
increase the expression of Nrf2, exert antioxidant action, and anti-inflammatory
effects in the experimental animals. The present study was designed to explore
the effects of TQ on CYP-induced hemorrhagic cystitis in Balb/c mice. Cystitis
was induced by a single intraperitoneal injection of CYP (200 mg/kg). TQ was
administered intraperitoneally at 5, 10 and 20 mg/kg doses twice a day, for three
days before and three days after the CYP administration. The efficacy of TQ was
determined in terms of the protection against the CYP-induced histological
perturbations in the bladder tissue, reduction in the oxidative stress, and
inhibition of the DNA fragmentation. Immunohistochemistry was performed to
examine the expression of Nrf2. TQ protected against CYP-induced oxidative stress
was evident from significant reduction in the lipid peroxidation, restoration of
the levels of reduced glutathione, catalase and superoxide dismutase activities.
TQ treatment significantly reduced the DNA damage evident as reduced DNA
fragmentation. A significant decrease in the cellular infiltration, edema,
epithelial denudation and hemorrhage were observed in the histological
observations. There was restoration and rise in the Nrf2 expression in the
bladder tissues of mice treated with TQ. These results confirm that, TQ
ameliorates the CYP-induced hemorrhagic cystitis in mice through reduction in the
oxidative stress, inhibition of the DNA damage and through increased expression
of Nrf2 in the bladder tissues.
PMID- 27489499
TI - The Involving Roles of Intrahepatic and Extrahepatic Stem/Progenitor Cells (SPCs)
to Liver Regeneration.
AB - Liver regeneration is usually attributed to mature hepatocytes, which possess a
remarkable potential to proliferate under mild to moderate injury. However, when
the liver is severely damaged or hepatocyte proliferation is greatly inhibited,
liver stem/progenitor cells (LSPCs) will contribute to the liver regeneration
process. LSPCs in the developing liver have been extensively characterized,
however, their contributing role to liver regeneration has not been completely
understood. In addition to the restoration of the liver parenchymal tissue by
hepatocytes or/and LSPCs, or in some cases bone marrow (BM) derived cells, such
as hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), the wound
healing after injury in terms of angiopoiesis by liver sinusoidal endothelial
cells (LSECs) or/and sinusoidal endothelial progenitor cells (SEPCs) is another
important aspect taking place during regeneration. To conclude, liver
regeneration can be mainly divided into three distinct restoring levels according
to the cause and severity of injury: hepatocyte dominant regeneration, LSPCs
mediated regeneration, extrahepatic stem cells participative regeneration. In
this review, we focus on the recent findings of liver regeneration, especially on
those related to stem/progenitor cells (SPCs)-mediated regeneration and their
potential clinical applications and challenges.
PMID- 27489500
TI - Selecting Cells for Bioartificial Liver Devices and the Importance of a 3D
Culture Environment: A Functional Comparison between the HepaRG and C3A Cell
Lines.
AB - Recently, the first clinical trials on Bioartificial Livers (BALs) loaded with a
proliferative human hepatocyte cell source have started. There are two cell lines
that are currently in an advanced state of BAL development; HepaRG and HepG2/C3A.
In this study we aimed to compare both cell lines on applicability in BALs and to
identify possible strategies for further improvement. We tested both cell lines
in monolayer- and BAL cultures on growth characteristics, hepatic
differentiation, nitrogen-, carbohydrate-, amino acid- and xenobiotic metabolism.
Interestingly, both cell lines adapted the hepatocyte phenotype more closely when
cultured in BALs; e.g. monolayer cultures produced lactate, while BAL cultures
showed diminished lactate production (C3A) or conversion to elimination (HepaRG),
and urea cycle activity increased upon BAL culturing in both cell lines. HepaRG
BALs outperformed C3A-BALs on xenobiotic metabolism, ammonia elimination and
lactate elimination, while protein synthesis was comparable. In BAL cultures of
both cell lines ammonia elimination correlated positively with glutamine
production and glutamate consumption, suggesting ammonia elimination was mainly
driven by the balance between glutaminase and glutamine synthetase activity. Both
cell lines lacked significant urea cycle activity and both required multiple
culture weeks before reaching optimal differentiation in BALs. In conclusion,
culturing in BALs enhanced hepatic functionality of both cell lines and from
these, the HepaRG cells are the most promising proliferative cell source for BAL
application.
PMID- 27489501
TI - BDNF-mediates Down-regulation of MicroRNA-195 Inhibits Ischemic Cardiac Apoptosis
in Rats.
AB - BACKGROUND: Our previous studies suggested that brain-derived neurotrophic factor
(BDNF)/tropomyosin-related kinase B (TrkB) axis inhibited cardiomyocyte apoptosis
in myocardial infarction (MI). However, the relationship between BDNF and
microRNA (miRNA) in cardiomyocytes are unclear. The present study was performed
to investigate the role of miR-195 and the interplay between BDNF and miR-195 in
ischemic cardiomyocyte apoptosis. METHODS: Male Wistar rats were subjected to
coronary artery ligation, and primary neonatal rat ventricular myocytes were
treated with hypoxia or hydrogen peroxide (H2O2). BDNF level in rat ventricles
was measured by enzyme linked immunosorbent assay (ELISA). miR-195 mimic,
inhibitor or negative control was transfected into the cardiomyocytes. Cell
viability and apoptosis were detected by MTT assay and TdT-mediated dUTP nick end
labeling (TUNEL) staining, respectively. Cardiac function and apoptosis were
detected in MI rats intravenously injected with antagomiR-195. Luciferase assay,
Western blot and Real-time RT-PCR were employed to clarify the interplay between
miR-195 and BDNF. RESULTS: miR-195 level was dynamically regulated in response to
MI and significantly increased in ischemic regions 24 h post-MI as well as in
hypoxic or H2O2-treated cardiomyocytes. Meanwhile, BDNF protein level was rapidly
increased in MI rats and H2O2-treated cardiomyocytes. Apoptosis in both hypoxic
and H2O2-treated cardiomyocytes were markedly reduced and cell viability was
increased by miR-195 inhibitor. Moreover, inhibition of miR-195 significantly
improved cardiac function of MI rats. Bcl-2 but not BDNF was validated as the
direct target of miR-195. Furthermore, BDNF abolished the pro-apoptotic role of
miR-195, which was reversed by its scavenger TrkB-Fc. CONCLUSION: Up-regulation
of miR-195 in ischemic cardiomyocytes promotes ischemic apoptosis by targeting
Bcl-2. BDNF mitigated the pro-apoptotic effect of miR-195 in rat cardiomyocytes.
These findings may provide better understanding of the pro-apoptotic role of miR
195 in MI and suggest that BDNF/miR-195/Bcl-2 axis may be beneficial for limiting
myocardial ischemic injury.
PMID- 27489502
TI - Fibroblast Growth Factor Receptor 3 Deficiency Does Not Impair the Osteoanabolic
Action of Parathyroid Hormone on Mice.
AB - PTH stimulates bone formation in Fgfr3 knockout mice through promotion of
proliferation and differentiation in osteoblasts. INTRODUCTION: Previous studies
showed that endogenous fibroblast growth factor 2 (FGF-2) is required for
parathyroid hormone (PTH)-stimulated bone anabolic effects, however, the exact
mechanisms by which PTH stimulate bone formation and the function of FGF
receptors in mediating these actions are not fully defined. FGF receptor 3
(FGFR3) has been characterized as an important regulator of bone metabolism and
is confirmed to cross-talk with PTH/PTHrP signal in cartilage and bone
development. METHODS: Fgfr3 knockout and wild-type mice at 2-month-old and 4
month-old were intraperitoneally injected with PTH intermittently for 4 weeks and
then the skeletal responses to PTH were assessed by dual energy X-ray
absorptiometry (DEXA), micro-computed tomography (MUCT) and bone
histomorphometry. RESULTS: Intermittent PTH treatment improved bone mineral
density (BMD) and femoral mechanical properties in both Fgfr3 (-/-) and wild-type
mice. Histomorphometric analysis showed that bone formation and bone resorption
were increased in both genotypes following PTH treatment. PTH treatment increased
trabecular bone volume (BV/TV) in WT and Fgfr3-deficient mice. The anabolic
response in Fgfr3-deficient and wild-type bone is characterized by an increase of
both bone formation and resorption-related genes following PTH treatment. In
addition, we found that Fgfr3 null osteoblasts (compared to wild-type controls)
maintained normal abilities to response to PTH-stimulated increase of
proliferation, differentiation, expression of osteoblastic marker genes (Cbfa1,
Osteopontin and Osteocalcin), and phosphorylation of Erk1/2. CONCLUSIONS: Bone
anabolic effects of PTH were not impaired by the absence of FGFR3, suggesting
that the FGFR3 signaling may not be required for osteoanabolic effects of PTH
activities.
PMID- 27489503
TI - Carbon Monoxide Improves Neurologic Outcomes by Mitochondrial Biogenesis after
Global Cerebral Ischemia Induced by Cardiac Arrest in Rats.
AB - Mitochondrial dysfunction contributes to brain injury following global cerebral
ischemia after cardiac arrest. Carbon monoxide treatment has shown potent
cytoprotective effects in ischemia/reperfusion injury. This study aimed to
investigate the effects of carbon monoxide-releasing molecules on brain
mitochondrial dysfunction and brain injury following resuscitation after cardiac
arrest in rats. A rat model of cardiac arrest was established by asphyxia. The
animals were randomly divided into the following 3 groups: cardiac arrest and
resuscitation group, cardiac arrest and resuscitation plus carbon monoxide
intervention group, and sham control group (no cardiac arrest). After the return
of spontaneous circulation, neurologic deficit scores (NDS) and S-100B levels
were significantly decreased at 24, 48, and 72 h, but carbon monoxide treatment
improved the NDS and S-100B levels at 24 h and the 3-day survival rates of the
rats. This treatment also decreased the number of damaged neurons in the
hippocampus CA1 area and increased the brain mitochondrial activity. In addition,
it increased mitochondrial biogenesis by increasing the expression of biogenesis
factors including peroxisome proliferator-activated receptor-gamma coactivator
1alpha, nuclear respiratory factor-1, nuclear respiratory factor-2 and
mitochondrial transcription factor A. Thus, this study showed that carbon
monoxide treatment alleviated brain injury after cardiac arrest in rats by
increased brain mitochondrial biogenesis.
PMID- 27489504
TI - Cis-Natural Antisense Transcripts Are Mainly Co-expressed with Their Sense
Transcripts and Primarily Related to Energy Metabolic Pathways during Muscle
Development.
AB - Cis-natural antisense transcripts (cis-NATs) are a new class of RNAs identified
in various species. However, the biological functions of cis-NATs are largely
unknown. In this study, we investigated the transcriptional characteristics and
functions of cis-NATs in the muscle tissue of lean Landrace and indigenous fatty
Lantang pigs. In total, 3,306 cis-NATs of 2,469 annotated genes were identified
in the muscle tissue of pigs. More than 1,300 cis-NATs correlated with their
sense genes at the transcriptional level, and approximately 80% of them were co
expressed in the two breeds. Furthermore, over 1,200 differentially expressed cis
NATs were identified during muscle development. Function annotation showed that
the cis-NATs participated in muscle development mainly by co-expressing with
genes involved in energy metabolic pathways, including citrate cycle (TCA cycle),
glycolysis or gluconeogenesis, mitochondrial activation and so on. Moreover,
these cis-NATs and their sense genes abruptly increased at the transition from
the late fetal stages to the early postnatal stages and then decreased along with
muscle development. In conclusion, the cis-NATs in the muscle tissue of pigs were
identified and determined to be mainly co-expressed with their sense genes. The
co-expressed cis-NATs and their sense gene were primarily related to energy
metabolic pathways during muscle development in pigs. Our results offered novel
evidence on the roles of cis-NATs during the muscle development of pigs.
PMID- 27489505
TI - A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.
AB - Neoadjuvant chemoradiotherapy has become the standard treatment for locally
advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor
size and recurrence, but also increase the tumor resection rate and anus
retention rate with very slight side effect. Comparing with preoperative
chemotherapy, preoperative chemoradiotherapy can further reduce the local
recurrence rate and downstage. Middle and low rectal cancers can benefit more
from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the
selection of appropriate patients and irradiation modes for neoadjuvant
chemoradiotherapy. Different therapeutic reactions to neoadjuvant
chemoradiotherapy affect the type of surgical techniques, hence calling for the
need of much attention. Furthermore, many problems such as accurate staging
before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and
sensitivity prediction to preoperative radiotherapy need to be well settled.
PMID- 27489506
TI - Rapamycin Reduced Ischemic Brain Damage in Diabetic Animals Is Associated with
Suppressions of mTOR and ERK1/2 Signaling.
AB - The objectives of the present study are to investigate the activation of mTOR and
ERK1/2 signaling after cerebral ischemia in diabetic rats and to examine the
neuroprotective effects of rapamycin. Ten minutes transient global cerebral
ischemia was induced in straptozotocin-induced diabetic hyperglycemic rats and
non-diabetic, euglycemic rats. Brain samples were harvested after 16 h of
reperfusion. Rapamycin or vehicle was injected 1 month prior to the induction of
ischemia. The results showed that diabetes increased ischemic neuronal cell death
and associated with elevations of p-P70S6K and Ras/ERK1/2 and suppression of p
AMPKalpha. Rapamycin ameliorated diabetes-enhanced ischemic brain damage and
suppressed phosphorylation of P70S6K and ERK1/2. It is concluded that diabetes
activates mTOR and ERK1/2 signaling pathways in rats subjected to transient
cerebral ischemia and inhibition of mTOR by rapamycin reduces ischemic brain
damage and suppresses the mTOR and ERK1/2 signaling in diabetic settings.
PMID- 27489507
TI - Rationing of nursing care interventions and its association with nurse-reported
outcomes in the neonatal intensive care unit: a cross-sectional survey.
AB - BACKGROUND: Evidence internationally suggests that staffing constraints and non
supportive work environments result in the rationing of nursing interventions
(that is, limiting or omitting interventions for particular patients), which in
turn may influence patient outcomes. In the neonatal intensive care unit (NICU),
preliminary studies have found that discharge preparation and infant comfort care
are among the most frequently rationed nursing interventions. However, it is
unknown if the rationing of discharge preparation is related to lower perceptions
of parent and infant readiness for NICU discharge, and if reports of increased
rationing of infant comfort care are related to lower levels of perceived
neonatal pain control. The purpose of this study was to assess these
relationships. METHODS: In late 2014, a cross-sectional survey was mailed to 285
Registered Nurses (RNs) working in one of 7 NICUs in the province of Quebec
(Canada). The survey contained validated measures of care rationing, parent and
infant readiness for discharge, and pain control, as well as items measuring RNs'
characteristics. Multivariate regression was used to examine the association
between care rationing, readiness for discharge and pain control, while adjusting
for RNs' characteristics and clustering within NICUs. RESULTS: Overall, 125 RNs
completed the survey; a 44.0 % response rate. Among the respondents, 28.0 and
40.0 % reported rationing discharge preparation and infant comfort care "often"
or "very often", respectively. Additionally, 15.2 % of respondents felt parents
and infants were underprepared for NICU discharge, and 54.4 % felt that pain was
not well managed on their unit. In multivariate analyses, the rationing of
discharge preparation was negatively related to RNs' perceptions of parent and
infant readiness for discharge, while reports of rationing of parental support
and teaching and infant comfort care were associated with less favourable
perceptions of neonatal pain control. CONCLUSIONS: The rationing of nursing
interventions appears to influence parent and infant readiness for discharge, as
well as pain control in NICUs. Future investigations, in neonatal nursing care as
well as in other nursing specialties, should address objectively measured patient
outcomes (such as objective pain assessments and post-discharge outcomes assessed
through administrative data).
PMID- 27489508
TI - A case report of asymptomatic aortic thrombosis incidentally detected by computed
tomography in apparently healthy subject with a history of cancer surgery.
AB - BACKGROUND: Aortic thrombosis is a rare disease and only a few cases of the
disease, especially associated with chemotherapy for malignant diseases and/or
blood diseases, have been previously reported. Although Virchow's triad for
thrombogenesis, namely hypercoagulability, blood flow stasis, and vessel wall
injury, is the major factor promoting the formation of thrombosis, the detailed
mechanism of the disease has not been well established. CASE PRESENTATION: We
report a case of aortic thrombosis incidentally detected by computed tomography
and then regressed by pharmacotherapy using warfarin. This case is an apparently
healthy man in a postoperative state after lung cancer surgery with decreased
protein-C activity. CONCLUSIONS: A case of aortic thrombosis without an obvious
abnormality of the aorta was incidentally identified. A few cases of aortic
thrombosis in healthy aortas have been reported to be associated with
chemotherapy or blood diseases, however our present case did not had such a
background. Although the detailed mechanism remains to be elucidated, this case
suggests that aortic thrombosis can develop in apparently healthy subjects with a
history of cancer surgery.
PMID- 27489509
TI - Rapid assessment of disability in the Philippines: understanding prevalence, well
being, and access to the community for people with disabilities to inform the W
DARE project.
AB - BACKGROUND: International recognition that people with disabilities were excluded
from the Millennium Development Goals has led to better inclusion of people with
disabilities in the recently agreed Global Goals for Sustainable Development
(SDGs) 2015-2030. Given the current global agenda for disability inclusion, it is
crucial to increase the understanding of the situation of people with
disabilities in the Philippines. The aim of this study was to estimate the
prevalence of disability and compare the well-being and access to the community
between people with and without disabilities. METHODS: A population-based survey
was undertaken in District 2 of Quezon City and in Ligao City. 60 clusters of 50
people aged 18 years and older were selected with probability proportion to size
sampling from both locations. The Rapid Assessment of Disability (RAD) survey was
used to identify people with disabilities based on their responses to activity
limitations. The levels of well-being and access to the community for people with
disabilities were compared with controls matched by age, gender, and cluster.
Information on barriers to accessing the community was also collected. RESULTS:
The prevalence of disability was 6.8 (95 % CI: 5.9, 7.9) and 13.6 % (95 % CI:
11.4, 16.2) in Quezon City and Ligao City respectively. Psychological distress
was the most commonly reported condition in both locations, although it was often
reported with a co-morbid condition related to sensory, physical, cognitive, and
communication difficulties. The prevalence of disability was associated with age
and no schooling, but not associated with poverty. People with disabilities had
significantly lower well-being scores and reduced access to health services,
work, rehabilitation, education, government social welfare, and disaster
management than people without disability. Having a disability and negative
family attitudes were reported as barriers for people with disabilities
participating in work, community meetings, religious activities, and social
activities. CONCLUSIONS: The prevalence of disability among adults in District 2
of Quezon City and in Ligao City is higher than the estimated national prevalence
of disability derived from the 2010 Philippines census. Disability is also
associated with lower well-being and reduced participation across a number of
domains of community life.
PMID- 27489510
TI - Socioeconomic status and self-rated health of Japanese people, based on age,
cohort, and period.
AB - BACKGROUND: Differences in health resulting from differences in socioeconomic
status (SES) have been identified around the world. Age, period, and cohort (A-P
C) differences in health are vital factors which are associated with disparities
in SES. However, few studies have examined these differences simultaneously.
Moreover, although self-rated health (SRH) has been frequently used as an
indicator of health, biases in reporting SRH that depend on the socioeconomic
characteristics of respondents have been scarcely adjusted in the previous
studies. To overcome these limitations, we investigated the associations between
disparities in SES and adjusted SRH based on A-P-C, by using a repeated, cross
sectional survey of a nationally representative sample of Japanese people. In
addition, we further investigated how exogenous (macroeconomic) conditions unique
to a period or cohort would explain trends across successive periods and cohorts.
METHODS: Data were obtained from a sample of 653,132 Japanese people that
responded to the Comprehensive Survey of Living Conditions (CSLC), which is a
cross-sectional survey that had been conducted every three years from 1986 to
2013, on over 10 occasions. In the CSLC, SES has been assessed by household
income. We simultaneously controlled for each A-P-C dimension by using the model
for cross-classification of random effects, and adjusting SRH data for reporting
biases caused by differences in income and A-P-C. RESULTS: Differences in
adjusted SRH associated with income differences decreased with age and reversed
after 76 years of age. Period differences indicated that income differences
peaked in 1992 and 2007. Moreover, differences in adjusted SRH associated with
income differences decreased in periods with high unemployment across all
periods. Furthermore, there were no cohort differences in adjusted SRH that were
associated with income differences. CONCLUSION: In Japan, there are age and
period variations associated with adjusted differences in SRH as assessed by
income. Moreover, exogenous conditions in each period could help explain periodic
trends across successive periods.
PMID- 27489511
TI - Tumour volumes: Predictors of early treatment response in locally advanced head
and neck cancers treated with definitive chemoradiation.
AB - AIM: To analyse and predict early response 3 months post definitive
chemoradiation (CCRT) utilising tumour volume (TV) measurement in locally
advanced head and neck cancers (LAHNC). BACKGROUND: LAHNC are 3-dimentional
lesions. The largest diameter of these tumours measured for T-classification may
not necessarily reflect the true tumour dimensions. TV accurately reflects the
tumour burden because it is a measurement of tumour burden in all three
dimensions. MATERIALS AND METHODS: It is a single institutional prospective study
including 101 patients with LAHNC treated with definitive CCRT. TV data noted
were primary tumour volume (PTV), total nodal volume (TNV) and total tumour
volume (TTV). Response evaluation was done at 3 months after the completion of
definitive CCRT and patients were categorised either having achieved complete
response (CR) or residual disease. RESULTS: Patients who had not achieved CR were
found to have larger TV compared with those who had achieved CR. There were
significant inverse correlations between PTV and response (median 16.37 cm(3) vs.
45.2 cm(3); p = 0.001), and between TTV and response (median 36.14 cm(3) vs.
66.06 cm(3); p < 0.001). Receiver operating characteristic (ROC) analysis
identified an "optimal cut-off" value of 41 cm(3) for PTV and 42 cm(3) for TTV
above and below which the magnitude of difference in response was the greatest.
CONCLUSIONS: If response evaluation 3 months post CCRT is to be predicted it is
simply not enough to measure the largest single dimension of the tumour. TV seems
to be a better and more accurate reflection of the true total tumour burden or
extent of the disease.
PMID- 27489512
TI - Superior sulcus non-small cell lung carcinoma: A comparison of IMRT and 3D-RT
dosimetry.
AB - AIM: A dosimetric study comparing intensity modulated radiotherapy (IMRT) by
TomoTherapy to conformational 3D radiotherapy (3D-RT) in patients with superior
sulcus non-small cell lung cancer (NSCLC). BACKGROUND: IMRT became the main
technique in modern radiotherapy. However it was not currently used for lung
cancers. Because of the need to increase the dose to control lung cancers but
because of the critical organs surrounding the tumors, the gains obtainable with
IMRT is not still demonstrated. MATERIAL AND METHODS: A dosimetric comparison of
the planned target and organs at risk parameters between IMRT and 3D-RT in eight
patients who received preoperative or curative intent irradiation. RESULTS: In
the patients who received at least 66 Gy, the mean V95% was significantly better
with IMRT than 3D-RT (p = 0.043). IMRT delivered a lower D2% compared to 3D-RT (p
= 0.043). The IH was significantly better with IMRT (p = 0.043). The lung V 5 Gy
and V 13 Gy were significantly higher in IMRT than 3D-RT (p = 0.043), while the
maximal dose (D max) to the spinal cord was significantly lower in IMRT (p =
0.043). The brachial plexus D max was significantly lower in IMRT than 3D-RT (p =
0.048). For patients treated with 46 Gy, no significant differences were found.
CONCLUSION: Our study showed that IMRT is relevant for SS-NSCLC. In patients
treated with a curative dose, it led to a reduction of the exposure of critical
organs, allowing a better dose distribution in the tumor. For the patients
treated with a preoperative schedule, our results provide a basis for future
controlled trials to improve the histological complete response by increasing the
radiation dose.
PMID- 27489513
TI - Volumetric Modulated Arc Therapy (VMAT) make a difference in retro-orbital
irradiation treatment of patients with bilateral Graves' ophthalmopathy.
Comparative analysis of dosimetric parameters from different radiation
techniques.
AB - BACKGROUND: Graves' ophthalmopathy is the commonest extrathyroidal manifestation
of Graves' disease. Treatment options include steroid therapy,
corrective/decompressive surgery, radiation therapy or combination of these
approaches. AIM: Our purpose was to investigate if retro-orbital irradiation with
Volumetric Modulated Arc Therapy (VMAT) yielded better target coverage and dose
sparing to adjacent normal structures compared to 3-Dimensional Conformal
Radiotherapy (3DCRT) and Lateral Opposing Conformed Fields (LOCF). METHODS:
Fourteen consecutive patients diagnosed with bilateral Graves' ophthalmopathy
were prospectively recruited into this study from August 2012 until August 2014.
An individual VMAT, 3DCRT and LOF plan was created for each patient. Conformity
Index (CI), Homogeneity Index (HI) and other dosimetric parameters of the targets
and organs-at-risk (OAR) were analyzed in all 28 orbits compared between the
different techniques. RESULTS: CI generated by VMAT was superior to that produced
by 3DCRT(p < .001) and LOF (p < .001). As expected, 3DCRT was also superior to
LOF (p = .007). Regarding the OARs sparing dose (lens, globes, retina and
lacrimal glands), VMAT showed a significant benefit when compared with 3DCRT and
LOCF, with no differences between the two latter techniques. CONCLUSIONS: VMAT
should be preferred over 3DCRT and LOF for bilateral Graves' ophthalmopathy
treatment.
PMID- 27489514
TI - Influence of the contrast agents on treatment planning dose calculations of
prostate and rectal cancers.
AB - AIM: The aim of the present study is to quantify differences in dose calculations
caused by using CA and determine if the resulting differences are clinically
significant. BACKGROUND: The influence of contrast agents (CA) on radiation dose
calculations must be taken into account in treatment planning. MATERIALS AND
METHODS: Eleven patients with pelvic cancers were included in this study and two
sets of CTs were taken for each patient (without and with CA) in the same
position and coordinates. Both sets of images were transferred to the DosiSoft
ISOgray treatment planning system for contouring and calculating the dose
distribution and monitor units (MUs) with Collapsed Cone and Superposition
algorithms, respectively. All plans were generated on pre-contrast CT and
subsequently copied to the post-contrast CT. Radiation dose calculations from the
two sets of CTs were compared using a paired sample t-test. RESULTS: The results
showed a statistically insignificant difference between pre- and post-contrast CT
treatment plans for target volume and OARs (p > 0.05), except bladder organ in
the prostate region (p < 0.05) but the relative mean dose and MU differences were
less than 2% in any patient for 18 MV photon beam. CONCLUSIONS: Treatment
planning on contrasted images generally showed a lower radiation dose to both
target volume and OARs than plans on non-contrasted images. The results of this
research showed that the small radiation dose differences between the plans for
the CT scans with and without CA seem to be clinically insignificant; therefore,
contrast-enhanced CT can be used for both target delineation and treatment
planning of prostate and rectal cancers.
PMID- 27489515
TI - Comparison of set-up errors by breast size on wing board by portal imaging.
AB - AIM: To quantify and compare setup errors between small and large breast patients
undergoing intact breast radiotherapy. METHODS: 20 patients were inducted. 10
small/moderate size breast in arm I and 10 large breast in arm II. Two orthogonal
and one lateral tangent portal images (PIs) were obtained and analyzed for
systematic (Sigma) and random (sigma) errors. Effect of no action level (NAL) was
also evaluated retrospectively. RESULTS: 142 PIs were analyzed. Sigma(mm) was 3.2
versus 6.7 (p = 0.41) in the mediolateral (ML) direction, 2.1 versus 2.9 (p =
0.06) in the craniocaudal (CC) and 2.2 versus 3.6 (p = 0.08) in the
anteroposterior (AP) direction in small and large breast, respectively. sigma(mm)
was 3.0, 3.3 and 3.3 for small breast and 4.1, 3.7 and 3.2 for large breast in
the ML, CC and AP direction (p = 0.07, 0.86, 0.37), respectively. 3 D Sigma(mm)
was 2.7 versus 4.2 (p = 0.01) and sigma(mm) was 2.5 versus 3.2 (p = 0.14) in arm
I and II, respectively. The standard deviation (SD) of variations (mm) in breast
contour depicted by central lung distance (CLD) was 5.9 versus 7.4 (p < 0.001),
central flash distance (CFD) 6.6 versus 10.5 (p = 0.002), inferior central margin
(ICM) 4 versus 4.9 (p < 0.001) in arm I and II, respectively. NAL showed a
significant reduction of systematic error in large breast in the mediolateral
direction only. CONCLUSION: Wing board can be used in a busy radiotherapy
department for setting up breast patients with a margin of 1.1 cm, 0.76 cm and
0.71 cm for small breasts and 1.96 cm, 1.12 cm and 0.98 cm for large breast in
the ML, AP and CC directions, respectively. The large PTV margin in the
mediolateral direction in large breast can be reduced using NAL. Further research
is needed to optimize positioning of large breasted women.
PMID- 27489516
TI - Study of the dosimetric differences between (192)Ir and (60)Co sources of high
dose rate brachytherapy for breast interstitial implant.
AB - AIM: The study intends to compare (192)Ir source against the (60)Co source for
interstitial breast metal implant in high dose rate brachytherapy. BACKGROUND:
Few studies have been reported to compare (60)Co and (192)Ir on HDR brachytherapy
in gynaecology and prostate cancer and very few with reference to breast cancer.
MATERIALS AND METHODS: Twenty patients who had undergone interstitial template
guided breast implant were treated in HDR (192)Ir brachytherapy unit. Plans were
generated substituting (60)Co source without changing the dwell positions and
optimization. Cumulative dose volume histograms were compared. RESULTS: The
reference isodose line enclosing CTV (CTVref) and the 2.34% difference seen in
the volume enclosed by the reference isodose line (V ref) between the two
isotopes show small but statistically significant difference (p < 0.05). In DHI,
no difference was observed in the relative dose between the two sources (p =
0.823). The over dose volume index showed 11% difference. The conformity index
showed 2.32% difference compared to (192)Ir (p < 0.05). D mean (%) and D max (%)
for the heart, ipsilateral lung, ipsilateral ribs, skin presented very small
difference. V 5% and V 10% of the heart shows 25% and 32% difference in dose. D
2cc (%) and D 0.1cc (%) for the contralateral breast, contralateral lung and D
2cc (%) of the skin displayed significant difference (p < 0.05). However, D 0.1cc
(%) of the skin indicated no noteworthy difference with p = 0.343. CONCLUSION:
Based on the 3D dosimetric analysis of patient plans considered in this study,
most of the DVH parameters showed statistically significant differences which can
be reduced by treatment planning optimization techniques. (60)Co isotope can be
used as a viable alternative because of its long half-life, logistic advantages
in procurement, infrequent need of source replacement and disposal of used
source.
PMID- 27489517
TI - Impact of reduction of flux overlap region on kilovoltage cone-beam computed
tomography image quality and patients' exposure dose.
AB - AIM: In high-precision radiation therapy, kilovoltage cone-beam computed
tomography plays an important role in verifying the position of patient and
localization of the target. However, the exposure dose is a problem with
kilovoltage cone-beam computed tomography. Flux overlap region increases the
patient dose around the center when the scan is performed in a full-scan mode. We
assessed the influence of flux overlap region in a full-scan mode to understand
the relationship between dose and image quality and investigated methods to
achieve a dose reduction. METHOD: A Catphan phantom was scanned using various
flux overlap region patterns in the pelvis on a full-scan mode. We used an
intensity-modulated radiation therapy phantom for measuring the central dose.
DoseLab was used to perform image analysis and to evaluate the linearity of the
computed tomography values, uniformity, high-contrast resolution, and contrast-to
noise ratio. RESULTS: The Hounsfield unit value varied by +/-40 Hounsfield unit
of the acceptance value for the X1 field size of 3.5 cm. However, there were no
differences in high-contrast resolution and contrast-to-noise ratio among
different scan patterns. The absorbed dose decreased by 7% at maximum for the
case within the tolerance value. CONCLUSION: Dose reduction is possible by
reducing the overlap region after calibration and by performing computed
tomography in the appropriate overlap region.
PMID- 27489518
TI - Outcome of radiotherapy for pituitary adenomas.
AB - AIM: The aim of this study was to analyze the outcome and toxicities and its
correlation to patient related and treatment related factors. BACKGROUND:
Pituitary adenomas are treated by radiation therapy (RT) as one of the modalities
along with surgery and medical therapy. RT to pituitary adenomas is a challenge
due to adjacent dose limiting structures such as optic apparatus and
hypothalamus. MATERIALS AND METHODS: Between January 2004 and December 2010, 94
patients treated for pituitary adenoma with RT who had hospital records of a
minimum follow-up of 1 year were included in the analysis. Tests of correlation
were done with regards to treatment factors. RESULTS: Male preponderance was
noted in our patient population. Nonfunctioning and functioning tumors were equal
in number in this series. Hypopituitarism was associated in 58.5% of patients
prior to RT. Radiological tumor progression was seen in one patient (1/94) who
had a nonfunctioning tumor. Among functioning tumors, biochemical remission was
seen in 93.6% of patients at a median follow-up of 6 years. CONCLUSIONS: Visual
complication was seen in 5.3% of patients and worsening or new onset
hypopituitarism was seen in 6.4%. Conventional 3-field technique was associated
with significantly more visual complication compared to Stereotactic Radiation
Therapy (SRT) technique. Doses <=50.4 Gy showed a trend of reduced rate of visual
and endocrine complications with no compromise in efficacy.
PMID- 27489519
TI - Dose distribution verification for GYN brachytherapy using EBT Gafchromic film
and TG-43 calculation.
AB - AIM: Verification of dose distributions for gynecological (GYN) brachytherapy
implants using EBT Gafchromic film. BACKGROUND: One major challenge in
brachytherapy is to verify the accuracy of dose distributions calculated by a
treatment planning system. MATERIALS AND METHODS: A new phantom was designed and
fabricated using 90 slabs of 18 cm * 16 cm * 0.2 cm Perspex to accommodate a
tandem and Ovoid assembly, which is normally used for GYN brachytherapy
treatment. This phantom design allows the use of EBT Gafchromic films for
dosimetric verification of GYN implants with a cobalt-60 HDR system or a LDR Cs
137 system. Gafchromic films were exposed using a plan that was designed to
deliver 1.5 Gy of dose to 0.5 cm distance from the lateral surface of ovoids from
a pair of ovoid assembly that was used for treatment vaginal cuff. For a
quantitative analysis of the results for both LDR and HDR systems, the measured
dose values at several points of interests were compared with the calculated data
from a commercially available treatment planning system. This planning system was
utilizing the TG-43 formalism and parameters for calculation of dose
distributions around a brachytherapy implant. RESULTS: The results of these
investigations indicated that the differences between the calculated and measured
data at different points were ranging from 2.4% to 3.8% for the LDR Cs-137 and
HDR Co-60 systems, respectively. CONCLUSION: The EBT Gafchromic films combined
with the newly designed phantom could be utilized for verification of the dose
distributions around different GYN implants treated with either LDR or HDR
brachytherapy procedures.
PMID- 27489520
TI - Accuracy in automatic image registration between MV cone beam computed tomography
and planning kV computed tomography in image guided radiotherapy.
AB - AIM: To verify the accuracy of automatic image registration (IR) between the
planning kilo voltage computed tomography (kV CT) and megavoltage cone beam
computed tomography (MV CBCT) datasets using phantom and patient images.
BACKGROUND: The automatic IR between MV CBCT and planning kV CT is a fast
solution for performing online image guided radiotherapy (IGRT). The IR accuracy
has to be verified periodically as it directly affects patient setup accuracy.
MATERIALS AND METHODS: The automatic IR accuracy was evaluated using image
quality phantom acquired with different kV CT slice thickness, different MV CBCT
acquisition MUs and reconstruction slice size and thickness. The IR accuracy was
also evaluated on patient images on different anatomical sites such as brain,
head & neck, thorax and pelvis. The uncertainty in the automatic registration was
assessed by introducing known offset to kV CT dataset and compared with the
registration results. RESULTS: The result with the phantom images was within 2 mm
in all three translational directions. The accuracy in automatic IR using patient
images was within 2 mm in most of the cases. 3 mm planning kV CT slice thickness
was sufficient to perform automatic IR successfully within 2 mm accuracy. The MV
CBCT reconstruction parameters such as slice thickness and slice size had no
effect on the registration accuracy. CONCLUSION: This study shows that the
automatic IR is accurate within 2 mm and provides confidence in performing them
between planning kV CT and MV CBCT image datasets for online image guided
radiotherapy.
PMID- 27489523
TI - New and Emerging Therapies.
PMID- 27489524
TI - A Review of New Surgical and Endoscopic Therapies for Gastroesophageal Reflux
Disease.
AB - Treatment of gastroesophageal reflux disease in the United States today is
binary, with the majority of patients with gastroesophageal reflux disease being
treated with antisecre-tory medications and a minority of patients, typically
those with volume regurgitation, undergoing Nissen fundoplication. However, there
has been increasing dissatisfaction with proton pump inhibitor therapy among a
significant number of patients with gastroesophageal reflux disease owing to
cost, side effects, and refractory symptoms, and there has been a general
reluctance to undergo surgical fundoplication due to its attendant side-effect
profile. As a result, a therapy gap exists for many patients with
gastroesophageal reflux disease. Alternative techniques are available for these
gap patients, including 2 endoscopic fundoplication techniques, an endoscopic
radiofrequency energy delivery technique, and 2 minimally invasive surgical
procedures. These alternative techniques have been extensively evaluated;
however, there are limitations to published studies, including arbitrary
definitions of success, variable efficacy measurements, deficient reporting
tools, inconsistent study designs, inconsistent lengths of follow-up
postintervention, and lack of comparison data across techniques. Although all of
the techniques appear to be safe, the endoscopic techniques lack demonstrable
reflux control and show variable symptom improvement and variable decreases in
proton pump inhibitor use. The surgical techniques are more robust, with evidence
for adequate reflux control, symptom improvement, and decreased proton pump
inhibitor use; however, these techniques are more difficult to perform and are
more intrusive. Additionally, these alternative techniques have only been studied
in patients with relatively normal anatomy. The field of gastroesophageal reflux
disease treatment is in need of consistent definitions of efficacy, standardized
study design and outcome measurements, and improved reporting tools before the
role of these techniques can be fully ascertained.
PMID- 27489522
TI - The NAD(+) precursor nicotinamide riboside decreases exercise performance in
rats.
AB - BACKGROUND: Nicotinamide adenine dinucleotide (NAD(+)) and its phosphorylated
form (NADP(+)) are key molecules in ubiquitous bioenergetic and cellular
signaling pathways, regulating cellular metabolism and homeostasis. Thus,
supplementation with NAD(+) and NADP(+) precursors emerged as a promising
strategy to gain many and multifaceted health benefits. In this proof-of-concept
study, we sought to investigate whether chronic nicotinamide riboside
administration (an NAD(+) precursor) affects exercise performance. METHODS:
Eighteen Wistar rats were equally divided in two groups that received either
saline vehicle or nicotinamide riboside at a dose of 300 mg/kg body weight/day
for 21 days via gavage. At the end of the 21-day administration protocol, both
groups performed an incremental swimming performance test. RESULTS: The
nicotinamide riboside group showed a tendency towards worse physical performance
by 35 % compared to the control group at the final 10 % load (94 +/- 53 s for the
nicotinamide riboside group and 145 +/- 59 s for the control group; P = 0.071).
CONCLUSION: Our results do not confirm the previously reported ergogenic effect
of nicotinamide riboside. The potentially negative effect of nicotinamide
riboside administration on physical performance may be attributed to the
pleiotropic metabolic and redox properties of NAD(+) and NADP(+).
PMID- 27489521
TI - Biotrophy at Its Best: Novel Findings and Unsolved Mysteries of the Arabidopsis
Powdery Mildew Pathosystem.
AB - It is generally accepted in plant-microbe interactions research that disease is
the exception rather than a common outcome of pathogen attack. However, in
nature, plants with symptoms that signify colonization by obligate biotrophic
powdery mildew fungi are omnipresent. The pervasiveness of the disease and the
fact that many economically important plants are prone to infection by powdery
mildew fungi drives research on this interaction. The competence of powdery
mildew fungi to establish and maintain true biotrophic relationships renders the
interaction a paramount example of a pathogenic plant-microbe biotrophy. However,
molecular details underlying the interaction are in many respects still a
mystery. Since its introduction in 1990, the Arabidopsis-powdery mildew
pathosystem has become a popular model to study molecular processes governing
powdery mildew infection. Due to the many advantages that the host Arabidopsis
offers in terms of molecular and genetic tools this pathosystem has great
capacity to answer some of the questions of how biotrophic pathogens overcome
plant defense and establish a persistent interaction that nourishes the invader
while in parallel maintaining viability of the plant host.
PMID- 27489526
TI - The Present and Future of Inflammatory Bowel Disease Treatment.
PMID- 27489525
TI - An Overview of the Evolution of Direct Cholangioscopy Techniques for Diagnosis
and Therapy.
AB - Direct examination of the biliary tree with endoscopes has been a challenge since
endoscopists began performing endoscopic retrograde cholangiopancreatography
(ERCP) in the late 1960s. Previously, surgeons had used rigid instruments
intraoperatively, which made examination difficult. The first direct
cholangioscopy performed by an endoscopist was likely unintentionally done in a
patient with postsurgical anatomy. Indirect imaging, ERCP, and percutaneous
transhepatic cholangiography are helpful modalities for examining the biliary
tree, but they are limited procedures, particularly with regard to the evaluation
and treatment of strictures and bile duct stones. This article reviews the
history and evolution of direct cholangioscopy since the advent of flexible
endoscopes. Additionally, the article describes a new single-operator cholan
gioscopy technique for direct visualization of the biliary tree for diagnosis and
intervention. There remains opportunity for innovation as endoscopists strive for
safe and less-invasive methods for the identification and treatment of biliary
pathology.
PMID- 27489527
TI - Update on Irritable Bowel Syndrome Diagnostics and Therapeutics.
PMID- 27489528
TI - Current and Emerging Treatments for Alpha-1 Antitrypsin Deficiency.
PMID- 27489529
TI - Updated Guidelines for Diagnosing and Managing Barrett Esophagus.
PMID- 27489530
TI - Primary Pancreatic Lymphoma Presenting as Acute Pancreatitis.
PMID- 27489531
TI - Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota
in sarcoidosis.
AB - Sarcoidosis is a systemic granulomatous disease of unknown etiology.
Granulomatous inflammation in sarcoidosis may affect multiple organs, including
the lungs, skin, CNS, and the eyes, leading to severe morbidity and mortality.
The underlying mechanisms for sustained inflammation in sarcoidosis are unknown.
We hypothesized that metabolic changes play a critical role in perpetuation of
inflammation in sarcoidosis. 1H nuclear magnetic resonance (NMR)-based untargeted
metabolomic analysis was used to identify circulating molecules in serum to
discriminate sarcoidosis patients from healthy controls. Principal component
analyses (PCA) were performed to identify different metabolic markers and explore
the changes of associated biochemical pathways. Using Chenomx 7.6 NMR Suite
software, we identified and quantified metabolites responsible for such
separation in the PCA models. Quantitative analysis showed that the levels of
metabolites, such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine,
homocysteine, pyruvate, and trimethylamine N-oxide were significantly increased
in sarcoidosis patients. Interestingly, succinate, a major intermediate
metabolite involved in the tricyclic acid cycle was significantly decreased in
sarcoidosis patients. Application of integrative pathway analyses identified
deregulation of butanoate, ketone bodies, citric cycle metabolisms, and
transmethylation. This may be used for development of new drugs or nutritional
modification.
PMID- 27489532
TI - Preclinical models for interrogating drug action in human cancers using Stable
Isotope Resolved Metabolomics (SIRM).
AB - AIMS: In this review we compare the advantages and disadvantages of different
model biological systems for determining the metabolic functions of cells in
complex environments, how they may change in different disease states, and
respond to therapeutic interventions. BACKGROUND: All preclinical drug-testing
models have advantages and drawbacks. We compare and contrast established cell,
organoid and animal models with ex vivo organ or tissue culture and in vivo human
experiments in the context of metabolic readout of drug efficacy. As metabolism
reports directly on the biochemical state of cells and tissues, it can be very
sensitive to drugs and/or other environmental changes. This is especially so when
metabolic activities are probed by stable isotope tracing methods, which can also
provide detailed mechanistic information on drug action. We have developed and
been applying Stable Isotope-Resolved Metabolomics (SIRM) to examine metabolic
reprogramming of human lung cancer cells in monoculture, in mouse
xenograft/explant models, and in lung cancer patients in situ (Lane et al. 2011;
T. W. Fan et al. 2011; T. W-M. Fan et al. 2012; T. W. Fan et al. 2012; Xie et al.
2014b; Ren et al. 2014a; Sellers et al. 2015b). We are able to determine the
influence of the tumor microenvironment using these models. We have now extended
the range of models to fresh human tissue slices, similar to those originally
described by O. Warburg (Warburg 1923), which retain the native tissue
architecture and heterogeneity with a paired benign versus cancer design under
defined cell culture conditions. This platform offers an unprecedented human
tissue model for preclinical studies on metabolic reprogramming of human cancer
cells in their tissue context, and response to drug treatment (Xie et al. 2014a).
As the microenvironment of the target human tissue is retained and individual
patient's response to drugs is obtained, this platform promises to transcend
current limitations of drug selection for clinical trials or treatments.
CONCLUSIONS AND FUTURE WORK: Development of ex vivo human tissue and animal
models with humanized organs including bone marrow and liver show considerable
promise for analyzing drug responses that are more relevant to humans. Similarly
using stable isotope tracer methods with these improved models in advanced stages
of the drug development pipeline, in conjunction with tissue biopsy is expected
significantly to reduce the high failure rate of experimental drugs in Phase II
and III clinical trials.
PMID- 27489533
TI - Partial Conservation between Mice and Humans in Olfactory Bulb Interneuron
Transcription Factor Codes.
AB - The mammalian main olfactory bulb (OB) has a large population of GABAergic
inhibitory interneurons that contains several subtypes defined by the co
expression other neurotransmitters and calcium binding proteins. The three most
commonly studied OB interneuron subtypes co-express either Calretinin, Calbindin,
or Tyrosine hydroxylase (Th). Combinations of transcription factors used to
specify the phenotype of progenitors are referred to as transcription factor
codes, and the current understanding of transcription factor codes that specify
OB inhibitory neuron phenotypes are largely based on studies in mice. The
conservation of these transcription factor codes in the human OB, however, has
not been investigated. The aim of this study was to establish whether
transcription factor codes in OB interneurons are conserved between mice and
humans. This study compared the co-expression of Foxp2, Meis2, Pax6, and Sp8
transcription factors with Calretinin, Calbindin, or Th in human and mouse OB
interneurons. This analysis found strong conservation of Calretinin co-expression
with Sp8 and Meis2 as well as Th co-expression with Pax6 and Meis2. This analysis
also showed that selective Foxp2 co-expression with Calbindin was conserved
between mice and humans, which suggests Foxp2 is a novel determinant of the OB
Calbindin interneuron phenotype. Together, the findings in this study provide
insight into the conservation of transcription codes for OB interneuron
phenotypes between humans and mice, as well as reveal some important differences
between the species. This advance in our understanding of transcription factor
codes in OB interneurons provides an important complement to the codes that have
been established for other regions within the mammalian central nervous system,
such as the cortex and spinal cord.
PMID- 27489534
TI - Salivary Stress-Related Responses in Tinnitus: A Preliminary Study in Young Male
Subjects with Tinnitus.
AB - OBJECTIVE: This preliminary study examined if baseline measures of stress-related
biomarkers as measured by salivary secretions of specific autonomic [measured by
salivary alpha-amylase (sAA)], endocrine (measured by salivary cortisol), and
immune (measured by salivary neopterin) responses are greater in male subjects
with tinnitus in response to an induced-stress task. METHOD: Twenty male subjects
with no significant hearing loss, 10 with tinnitus, and 10 without tinnitus were
enrolled in this study.Salivary secretions were collected before and after the
induced stress task at four different time intervals. RESULTS: sAA levels were
lower in the tinnitus group in comparison to subjects without tinnitus,
suggesting impaired sympathetic activity in the subjects with tinnitus although
these levels remained stable throughout the stress experiment.While no
significant effects could be obtained for salivary cortisol or neopterin,
salivary neopterin levels were trending toward significance over all
measurements. Behavioral measures of stress were found to correlate negatively
with measures of sAA and salivary neopterin. CONCLUSION: The results of this
study suggest impaired stress-related sAA mechanisms in male subjects with
tinnitus, as evidenced by the different stress reactions induced in the endocrine
system (as measured by salivary cortisol) and the immune system (as measured by
salivary neopterin).
PMID- 27489535
TI - Learning and Memory Deficits in Male Adult Mice Treated with a Benzodiazepine
Sleep-Inducing Drug during the Juvenile Period.
AB - Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the
mammalian central nervous system, is also known to be important for brain
development. Therefore, disturbances of GABA receptor (GABA-R) mediated signaling
(GABA-R signal) during brain development may influence normal brain maturation
and cause late-onset brain malfunctions. In this study, we examined whether the
stimulation of the GABA-R signal during brain development induces late-onset
adverse effects on the brain in adult male mice. To stimulate the GABA-R signal,
we used either the benzodiazepine sleep-inducing drug triazolam (TZ) or the non
benzodiazepine drug zolpidem (ZP). We detected learning and memory deficits in
mice treated with TZ during the juvenile period, as seen in the fear conditioning
test. On the other hand, ZP administration during the juvenile period had little
effect. In addition, decreased protein expression of GluR1 and GluR4, which are
excitatory neurotransmitter receptors, was detected in the hippocampi of mice
treated with TZ during the juvenile period. We measured mRNA expression of the
immediate early genes (IEGs), which are neuronal activity markers, in the
hippocampus shortly after the administration of TZ or ZP to juvenile mice.
Decreased IEG expression was detected in mice with juvenile TZ administration,
but not in mice with juvenile ZP administration. Our findings demonstrate that TZ
administration during the juvenile period can induce irreversible learning and
memory deficits in adult mice. It may need to take an extra care for the
prescription of benzodiazepine sleep-inducing drugs to juveniles because it might
cause learning and memory deficits.
PMID- 27489536
TI - Neural Activation during Anticipation of Near Pain-Threshold Stimulation among
the Pain-Fearful.
AB - Fear of pain (FOP) can increase risk for chronic pain and disability but little
is known about corresponding neural responses in anticipation of potential pain.
In this study, more (10 women, 6 men) and less (7 women, 6 men) pain-fearful
groups underwent whole-brain functional magnetic resonance imaging (fMRI) during
anticipation of near pain-threshold stimulation. Groups did not differ in the
proportion of stimuli judged to be painful but pain-fearful participants reported
significantly more state fear prior to stimulus exposure. Within the entire
sample, stronger activation was found in several pain perception regions (e.g.,
bilateral insula, midcingulate cortex (MCC), thalamus, superior frontal gyrus)
and visual areas linked to decoding stimulus valences (inferior orbital cortex)
during anticipation of "painful" stimuli. Between groups and correlation analyses
indicated pain-fearful participants experienced comparatively more activity in
regions implicated in evaluating potential threats and processing negative
emotions during anticipation (i.e., MCC, mid occipital cortex, superior temporal
pole), though group differences were not apparent in most so-called "pain matrix"
regions. In sum, trait- and task-based FOP is associated with enhanced
responsiveness in regions involved in threat processing and negative affect
during anticipation of potentially painful stimulation.
PMID- 27489537
TI - What Does Cytochrome Oxidase Histochemistry Represent in the Visual Cortex?
PMID- 27489538
TI - Knockout of Cyclophilin-D Provides Partial Amelioration of Intrinsic and Synaptic
Properties Altered by Mild Traumatic Brain Injury.
AB - Mitochondria are central to cell survival and Ca(2+) homeostasis due to their
intracellular buffering capabilities. Mitochondrial dysfunction resulting in
mitochondrial permeability transition pore (mPTP) opening has been reported after
mild traumatic brain injury (mTBI). Cyclosporine A provides protection against
the mPTP opening through its interaction with cyclophilin-D (CypD). A recent
study has found that the extent of axonal injury after mTBI was diminished in
neocortex in cyclophilin-D knockout (CypDKO) mice. Here we tested whether this
CypDKO could also provide protection from the increased intrinsic and synaptic
neuronal excitability previously described after mTBI in a mild central fluid
percussion injury mice model. CypDKO mice were crossed with mice expressing
yellow fluorescent protein (YFP) in layer V pyramidal neurons in neocortex to
create CypDKO/YFP-H mice. Whole cell patch clamp recordings from axotomized (AX)
and intact (IN) YFP+ layer V pyramidal neurons were made 1 and 2 days after sham
or mTBI in slices from CypDKO/YFP-H mice. Both excitatory post synaptic currents
(EPSCs) recorded in voltage clamp and intrinsic cellular properties, including
action potential (AP), afterhyperpolarization (AHP), and depolarizing after
potential (DAP) characteristics recorded in current clamp were evaluated. There
was no significant difference between sham and mTBI for either spontaneous or
miniature EPSC frequency, suggesting that CypDKO ameliorates excitatory synaptic
abnormalities. There was a partial amelioration of intrinsic properties altered
by mTBI. Alleviated were the increased slope of the AP frequency vs. injected
current plot, the increased AP, AHP and DAP amplitudes. Other properties that saw
a reversal that became significant in the opposite direction include the current
rheobase and AP overshoot. The AP threshold remained depolarized and the input
resistance remained increased in mTBI compared to sham. Additional altered
properties suggest that the CypDKO likely has a direct effect on membrane
properties, rather than producing a selective reduction of the effects of mTBI.
These results suggest that inhibiting CypD after TBI is an effective strategy to
reduce synaptic hyperexcitation, making it a continued target for potential
treatment of network abnormalities.
PMID- 27489539
TI - Role of Astroglial Hemichannels and Pannexons in Memory and Neurodegenerative
Diseases.
AB - Under physiological conditions, astroglial hemichannels and pannexons allow the
release of gliotransmitters from astrocytes. These gliotransmitters are critical
in modulating synaptic transmission, plasticity and memory. However, recent
evidence suggests that under pathological conditions, they may be central in the
development of various neurodegenerative diseases. Here we review current
literature on the role of astroglial hemichannels and pannexons in memory, stress
and the development of neurodegenerative diseases, and propose that they are not
only crucial for normal brain function, including memory, but also a potential
target for the treatment of neurodegenerative diseases.
PMID- 27489540
TI - Adolescent Social Defeat Induced Alterations in Social Behavior and Cognitive
Flexibility in Adult Mice: Effects of Developmental Stage and Social Condition.
AB - Negative social experiences during adolescence increase the risk of psychiatric
disorders in adulthood. Using "resident-intruder" stress, the present study aimed
to investigate the effects of adolescent social defeat on emotional and cognitive
symptoms associated with psychiatric disorders during adulthood and the effects
of the developmental stage and social condition on this process. In Experiment 1,
animals were exposed to social defeat or manipulation for 10 days during early
adolescence (EA, postnatal days [PND] 28-37), late adolescence (LA, PND 38-47),
and adulthood (ADULT, PND 70-79) and then singly housed until the behavioral
tests. Behaviors, including social avoidance of the defeat context and cortically
mediated cognitive flexibility in an attentional set-shifting task (AST), were
assessed during the week following stress or after 6 weeks during adulthood. We
determined that social defeat induced significant and continuous social avoidance
across age groups at both time points. The mice that experienced social defeat
during adulthood exhibited short-term impairments in reversal learning (RL) on
the AST that dissipated after 6 weeks. In contrast, social defeat during EA but
not LA induced a delayed deficit in extra-dimensional set-shifting (EDS) in
adulthood but not during adolescence. In Experiment 2, we further examined the
effects of social condition (isolation or social housing after stress) on the
alterations induced by social defeat during EA in adult mice. The adult mice that
had experienced stress during EA exhibited social avoidance similar to the
avoidance identified in Experiment 1 regardless of the isolation or social
housing after the stress. However, social housing after the stress ameliorated
the cognitive flexibility deficits induced by early adolescent social defeat in
the adult mice, and the social condition had no effect on cognitive function.
These findings suggest that the effects of social defeat on emotion and cognitive
function are differentially affected by the developmental stage and social
condition. EA may comprise a particularly sensitive developmental period in which
social defeat may produce a delayed impairment in cognitive flexibility during
adulthood, and the social condition following stress appears to play an important
intermediary role in the development of these cognitive deficits.
PMID- 27489541
TI - Emotion Discrimination Using Spatially Compact Regions of Interest Extracted from
Imaging EEG Activity.
AB - Lately, research on computational models of emotion had been getting much
attention due to their potential for understanding the mechanisms of emotions and
their promising broad range of applications that potentially bridge the gap
between human and machine interactions. We propose a new method for emotion
classification that relies on features extracted from those active brain areas
that are most likely related to emotions. To this end, we carry out the selection
of spatially compact regions of interest that are computed using the brain neural
activity reconstructed from Electroencephalography data. Throughout this study,
we consider three representative feature extraction methods widely applied to
emotion detection tasks, including Power spectral density, Wavelet, and Hjorth
parameters. Further feature selection is carried out using principal component
analysis. For validation purpose, these features are used to feed a support
vector machine classifier that is trained under the leave-one-out cross
validation strategy. Obtained results on real affective data show that
incorporation of the proposed training method in combination with the enhanced
spatial resolution provided by the source estimation allows improving the
performed accuracy of discrimination in most of the considered emotions, namely:
dominance, valence, and liking.
PMID- 27489542
TI - Successful Multidisciplinary Treatment with Secondary Metastatic Liver Resection
after Downsizing by Palliative Second-Line Treatment of Colorectal Cancer: A
Curative Option.
AB - INTRODUCTION: The prognostic outcome following progression after palliative first
line treatment for patients suffering from metastatic colorectal adenocarcinoma
is generally poor. Long-term relapse-free survival with palliative second-line
treatment may be achieved in only a limited number of individual cases. CASE
REPORT: A 37-year-old patient presented with bilobar liver metastases of colon
cancer confirmed by histology with wild-type K-RAS (exon 2). Due to progressive
disease after eight cycles of first-line therapy with FOLFIRI plus cetuximab,
second-line chemotherapy with modified FOLFOX4 (mFOLFOX4) plus bevacizumab was
initiated. During four cycles of mFOLFOX4 plus bevacizumab (2 months), no higher
grade toxicity occurred. Liver MRI with contrast medium revealed downsizing of
the segment II/III metastases, as well as regressive, small, faint, hardly
definable lesions in segments VI and IVb. The interdisciplinary tumor board of
the University of Erlangen thus decided to perform resection of the liver
metastases. Segments II and III were resected, and the liver metastases in
segments IVa and VI were excised (R0). Histopathology confirmed three of the R0
resected metastases to be completely necrotic, with residual scarring. As
perioperative therapy, four additional cycles of mFOLFOX4 plus bevacizumab were
administered postoperatively. No higher-grade toxicity was observed. Three years
after the initial diagnosis, the patient is relapse free, professionally fully
reintegrated, and has an excellent performance status. CONCLUSION: Patients
suffering from metastatic colorectal cancer may benefit from multidisciplinary
treatment with secondary metastatic liver resection after downsizing by
palliative second-line treatment. In individual cases, patients may even have a
curative treatment option, provided that close interdisciplinary collaboration
exists.
PMID- 27489544
TI - Prescription Factors Associated with Medication Non-adherence in Japan Assessed
from Leftover Drugs in the SETSUYAKU-BAG Campaign: Focus on Oral Antidiabetic
Drugs.
AB - BACKGROUND: Medication adherence has an important influence on health outcomes in
patients with chronic diseases. However, few studies have been performed in Japan
to determine factors related to medication non-adherence. OBJECTIVE: The aim of
this study was to identify prescription factors related to medication non
adherence by investigating patient characteristics, all prescriptions, and
prescriptions for oral antidiabetic drugs (OADs). METHODS: A retrospective cross
sectional survey of prescription data about implementation of dosing regimen was
performed at community pharmacies engaged in appropriate use of leftover drugs.
We evaluated the amount of drugs originally prescribed and the reduced amount
after use of leftover drugs, and then calculated prescription reduction ratio
(PRR). We analyzed prescription factors contributing to non-adherence based on
the PRR. RESULTS: Prescription information for 1207 patients was reviewed,
revealing that patients were non-adherent to 58% of prescriptions. Lack of a drug
copayment, fewer concurrent drugs, and drugs not in single-dose packaging were
associated with non-adherence. Among the 1207 patients, 234 prescriptions for
diabetes and 452 OAD formulations were included. Forty-seven percent of
prescriptions and 29% of the formulations were non-adherent. A higher dosing
frequency and preprandial administration were associated with non-adherence.
Among the OADs, adherence was lower for alpha-glucosidase inhibitors and
biguanides than for sulfonylureas. CONCLUSIONS: Several factors related to
patient characteristics, general drug prescriptions, and OAD prescriptions were
associated with non-adherence. Further consideration will be needed to improve
adherence to medication in Japan. Health care providers should perform more
careful monitoring of adherence in patients with the factors identified by this
study.
PMID- 27489543
TI - False Recognition in Behavioral Variant Frontotemporal Dementia and Alzheimer's
Disease-Disinhibition or Amnesia?
AB - Episodic memory recall processes in Alzheimer's disease (AD) and behavioral
variant frontotemporal dementia (bvFTD) can be similarly impaired, whereas
recognition performance is more variable. A potential reason for this variability
could be false-positive errors made on recognition trials and whether these
errors are due to amnesia per se or a general over-endorsement of recognition
items regardless of memory. The current study addressed this issue by analysing
recognition performance on the Rey Auditory Verbal Learning Test (RAVLT) in 39
bvFTD, 77 AD and 61 control participants from two centers (India, Australia), as
well as disinhibition assessed using the Hayling test. Whereas both AD and bvFTD
patients were comparably impaired on delayed recall, bvFTD patients showed intact
recognition performance in terms of the number of correct hits. However, both
patient groups endorsed significantly more false-positives than controls, and
bvFTD and AD patients scored equally poorly on a sensitivity index (correct hits
false-positives). Furthermore, measures of disinhibition were significantly
associated with false positives in both groups, with a stronger relationship with
false-positives in bvFTD. Voxel-based morphometry analyses revealed similar
neural correlates of false positive endorsement across bvFTD and AD, with both
patient groups showing involvement of prefrontal and Papez circuitry regions,
such as medial temporal and thalamic regions, and a DTI analysis detected an
emerging but non-significant trend between false positives and decreased fornix
integrity in bvFTD only. These findings suggest that false-positive errors on
recognition tests relate to similar mechanisms in bvFTD and AD, reflecting
deficits in episodic memory processes and disinhibition. These findings highlight
that current memory tests are not sufficient to accurately distinguish between
bvFTD and AD patients.
PMID- 27489546
TI - Corrigendum: Transient Hepatic Overexpression of Insulin-Like Growth Factor 2
Induces Free Cholesterol and Lipid Droplet Formation.
AB - [This corrects the article on p. 147 in vol. 7, PMID: 27199763.].
PMID- 27489545
TI - Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and
Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.
AB - In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated
respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA)
and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by
selective COX-2 inhibitors. The mechanism involved is related to prostaglandin
pathway inhibition and leukotriene release. Subjects who react to a single NSAID
and tolerate others are considered selective responders, and often present
urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism
is implicated in these reactions. However, anecdotal evidence suggests that
selective responders who present respiratory airway symptoms may also exist. Our
objective was to determine if subjects might develop selective responses to
NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For
this purpose, we studied patients reporting asthma and/or rhinitis induced by
paracetamol or a single NSAID that tolerated ASA. An allergological evaluation
plus controlled challenge with ASA was carried out. If ASA tolerance was found,
we proceeded with an oral challenge with the culprit drug. The appearance of
symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or
nasal airways volume changes pre and post challenge. From a total of 21 initial
cases, we confirmed the appearance of nasal and/or bronchial manifestations in
ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal
volume cavity after drug administration. All cases tolerated ASA. This shows that
ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a
single NSAID without skin/systemic manifestations exist. Whether these patients
represent a new clinical phenotype to be included within the current
classification of hypersensitivity reactions to NSAIDs requires further
investigation.
PMID- 27489548
TI - Corrigendum: Detecting Deception within Small Groups: A Literature Review.
AB - [This corrects the article on p. 1012 in vol. 7, PMID: 27445957.].
PMID- 27489547
TI - Mirror Neurons System Engagement in Late Adolescents and Adults While Viewing
Emotional Gestures.
AB - Observing others' actions enhances muscle-specific cortico-spinal excitability,
reflecting putative mirror neurons activity. The exposure to emotional stimuli
also modulates cortico-spinal excitability. We investigated how those two
phenomena might interact when they are combined, i.e., while observing a gesture
performed with an emotion, and whether they change during the transition between
adolescence and adulthood, a period of social and brain maturation. We delivered
single-pulse transcranial magnetic stimulation (TMS) over the hand area of the
left primary motor cortex of 27 healthy adults and adolescents and recorded their
right first dorsal interossus (FDI) muscle activity (i.e., motor evoked potential
- MEP), while they viewed either videos of neutral or angry hand actions and
facial expressions, or neutral objects as a control condition. We reproduced the
motor resonance and the emotion effects - hand-actions and emotional stimuli
induced greater cortico-spinal excitability than the faces/control condition and
neutral videos, respectively. Moreover, the influence of emotion was present for
faces but not for hand actions, indicating that the motor resonance and the
emotion effects might be non-additive. While motor resonance was observed in both
groups, the emotion effect was present only in adults and not in adolescents. We
discuss the possible neural bases of these findings.
PMID- 27489549
TI - Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion
in Physiological and Pathophysiological Conditions.
AB - In the normal human adrenal gland, steroid secretion is regulated by a complex
network of autocrine/paracrine interactions involving bioactive signals released
by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells,
and adrenocortical cells themselves. ACTH can be locally produced by medullary
chromaffin cells and is, therefore, a major mediator of the corticomedullary
functional interplay. Plasma ACTH also triggers the release of angiogenic and
vasoactive agents from adrenocortical cells and adrenal mast cells and, thus,
indirectly regulates steroid production through modulation of the adrenal blood
flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit
molecular and cellular defects that tend to reinforce the influence of paracrine
regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be
abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible
for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of
adrenocortical cells that express gonadal markers. This observation suggests that
ectopic production of ACTH may result from impaired embryogenesis leading to
abnormal maturation of the adrenogonadal primordium. Globally, the current
literature indicates that ACTH is a major player in the autocrine/paracrine
processes occurring in the adrenal gland in both physiological and pathological
conditions.
PMID- 27489550
TI - Genetic Dissection of the Regulatory Network Associated with High c-di-GMP Levels
in Pseudomonas putida KT2440.
AB - Most bacteria grow in nature forming multicellular structures named biofilms. The
bacterial second messenger cyclic diguanosine monophosphate (c-di-GMP) is a key
player in the regulation of the transition from planktonic to sessile lifestyles
and this regulation is crucial in the development of biofilms. In Pseudomonas
putida KT2440, Rup4959, a multidomain response regulator with diguanylate cyclase
activity, when overexpressed causes an increment in the intracellular levels of c
di-GMP that gives rise to a pleiotropic phenotype consisting of increased biofilm
formation and crinkly colony morphology. In a broad genomic screen we have
isolated mutant derivatives that lose the crinkly morphology, designed as cfc
(crinkle free colony). A total of 19 different genes have been identified as
being related with the emergence of the cfc phenotype either because the
expression or functionality of Rup4959 is compromised, or due to a lack of
transduction of the c-di-GMP signal to downstream elements involved in the
acquisition of the phenotype. Discernment between these possibilities was
investigated by using a c-di-GMP biosensor and by HPLC-MS quantification of the
second messenger. Interestingly five of the identified genes encode proteins with
AAA+ ATPase domain. Among the bacterial determinants found in this screen are the
global transcriptional regulators GacA, AlgU and FleQ and two enzymes involved in
the arginine biosynthesis pathway. We present evidences that this pathway seems
to be an important element to both the availability of the free pool of the
second messenger c-di-GMP and to its further transduction as a signal for
biosynthesis of biopolimers. In addition we have identified an uncharacterized
hybrid sensor histidine kinase whose phosphoaceptor conserved histidine residue
has been shown in this work to be required for in vivo activation of the orphan
response regulator Rup4959, which suggests these two elements constitute a two
component phosphorelay system.
PMID- 27489551
TI - Environmental Conditions Outweigh Geographical Contiguity in Determining the
Similarity of nifH-Harboring Microbial Communities in Sediments of Two
Disconnected Marginal Seas.
AB - Ecological evidence suggests that heterotrophic diazotrophs fueled by organic
carbon respiration in sediments play an important role in marine nitrogen
fixation. However, fundamental knowledge about the identities, abundance,
diversity, biogeography, and controlling environmental factors of nitrogen-fixing
communities in open ocean sediments is still elusive. Surprisingly, little is
known also about nitrogen-fixing communities in sediments of the more research
accessible marginal seas. Here we report on an investigation of the environmental
geochemistry and putative diazotrophic microbiota in the sediments of Bohai Sea,
an eutrophic marginal sea of the western Pacific Ocean. Diverse and abundant nifH
gene sequences were identified and sulfate-reducing bacteria (SRB) were found to
be the dominant putative nitrogen-fixing microbes. Community statistical analyses
suggested bottom water temperature, bottom water chlorophyll a content (or the
covarying turbidity) and sediment porewater Eh (or the covarying pH) as the most
significant environmental factors controlling the structure and spatial
distribution of the putative diazotrophic communities, while sediment Hg content,
sulfide content, and porewater [Formula: see text]-Si content were identified as
the key environmental factors correlated positively with the nifH gene abundance
in Bohai Sea sediments. Comparative analyses between the Bohai Sea and the
northern South China Sea (nSCS) identified a significant composition difference
of the putative diazotrophic communities in sediments between the shallow-water
(estuarine and nearshore) and deep-water (offshore and deep-sea) environments,
and sediment porewater dissolved oxygen content, water depth and in situ
temperature as the key environmental factors tentatively controlling the species
composition, community structure, and spatial distribution of the marginal sea
sediment nifH-harboring microbiota. This confirms the ecophysiological
specialization and niche differentiation between the shallow-water and deep-water
sediment diazotrophic communities and suggests that the in situ physical and
geochemical conditions play a more important role than geographical contiguity in
determining the community similarity of the diazotrophic microbiota in marginal
sea sediments.
PMID- 27489552
TI - Cytochrome c as a Potentially Clinical Useful Marker of Mitochondrial and
Cellular Damage.
AB - Mitochondria are evolutionary endosymbionts derived from bacteria. Thus, they
bear molecules, such as mitochondrial DNA (mtDNA) that contains CpG DNA repeats
and N-formyl peptides (FPs), found in bacteria. Upon cell necrosis or apoptosis,
these molecules are released into the interstitial space and the circulation and
recognized by the immune cells through the same receptors that recognize pathogen
associated molecular patterns, leading to inflammation. Other mitochondrial
molecules are not of bacterial origin, but they may serve as danger-associated
molecular patterns (DAMPs) when due to cell injury are translocated into
inappropriate compartments. There they are recognized by pattern recognition
receptors of the immune cells. Cytochrome c is such a molecule. In this review,
experimental and clinical data are presented that confirms cytochrome c release
into the extracellular space in pathological conditions characterized by cell
death. This indicates that serum cytochrome c, which can be easily measured, may
be a clinically useful marker for diagnosing and assessing the severity of such
pathological entities. Reasonably, detection of high cytochrome c level into the
circulation means release of various other molecules that serves as DAMPs when
found extracellularly, the mtDNA and FPs included. Finally, because the release
of this universally found compound into the extracellular space makes cytochrome
c an ideal molecule to play the role of a DAMP per se, the available experimental
and clinical data that support such a role are provided.
PMID- 27489553
TI - Increased Needle Nitrogen Contents Did Not Improve Shoot Photosynthetic
Performance of Mature Nitrogen-Poor Scots Pine Trees.
AB - Numerous studies have shown that temperate and boreal forests are limited by
nitrogen (N) availability. However, few studies have provided a detailed account
of how carbon (C) acquisition of such forests reacts to increasing N supply. We
combined measurements of needle-scale biochemical photosynthetic capacities and
continuous observations of shoot-scale photosynthetic performance from several
canopy positions with simple mechanistic modeling to evaluate the photosynthetic
responses of mature N-poor boreal Pinus sylvestris to N fertilization. The
measurements were carried out in August 2013 on 90-year-old pine trees growing at
Rosinedalsheden research site in northern Sweden. In spite of a nearly doubling
of needle N content in response to the fertilization, no effect on the long-term
shoot-scale C uptake was recorded. This lack of N-effect was due to strong light
limitation of photosynthesis in all investigated canopy positions. The effect of
greater N availability on needle photosynthetic capacities was also constrained
by development of foliar phosphorus (P) deficiency following N addition. Thus, P
deficiency and accumulation of N in arginine appeared to contribute toward lower
shoot-scale nitrogen-use efficiency in the fertilized trees, thereby additionally
constraining tree-scale responses to increasing N availability. On the whole our
study suggests that the C uptake response of the studied N-poor boreal P.
sylvestris stand to enhanced N availability is constrained by the efficiency with
which the additional N is utilized. This efficiency, in turn, depends on the
ability of the trees to use the greater N availability for additional light
capture. For stands that have not reached canopy closure, increase in leaf area
following N fertilization would be the most effective way for improving light
capture and C uptake while for mature stands an increased leaf area may have a
rather limited effect on light capture owing to increased self-shading. This
raises the question if N limitation in boreal forests acts primarily by
constraining growth of young stands while the commonly recorded increase in stem
growth of mature stands following N addition is primarily the result of altered
allocation and only to a limited extent the result of increased stand C-capture.
PMID- 27489554
TI - Nutritional and Sensory Evaluation of Injera Prepared from tef and Eragrostis
curvula (Schrad.) Nees. Flours with Sorghum Blends.
AB - Injera is a fermented, sour bread consumed as a staple food in Eritrea and
Ethiopia. The bread can be prepared from various cereals but tef [Eragrostis tef
(Zucc.) Trotter] is the most preferred ingredient. This study assessed the
acceptability of injera prepared using grains of a closely related but
underutilized grass, Eragrostis curvula (Schrad.) Nees. The nutritive value of
the grains was compared and the sensory attributes of injera made from flours of
tef (control) and E. curvula, each combined with 0, 5, and 10% of sorghum flour,
were assessed using a tasting panel. Nutrient analysis showed that E. curvula
contains more than double the amount of crude protein found in tef. E. curvula
also contains higher fat, dietary fiber and mineral nutrients than tef. Injera
made of E. tef and E. curvula flours showed non-significant differences in taste,
texture, appearance and overall acceptability. This suggest that E. curvula has
the potential to serve as a novel source of gluten-free flour for human
consumption. Agronomically viewed, growing E. curvula could be more advantageous
for smallholder farmers on marginal lands because the species is a perennial that
can produce a seed harvest twice a year, unlike tef, which is annual crop. It
also tolerates acidic soils better than tef.
PMID- 27489555
TI - Mutation of Gly195 of the ChlH Subunit of Mg-chelatase Reduces Chlorophyll and
Further Disrupts PS II Assembly in a Ycf48-Deficient Strain of Synechocystis sp.
PCC 6803.
AB - Biogenesis of the photosystems in oxygenic phototrophs requires co-translational
insertion of chlorophyll a. The first committed step of chlorophyll a
biosynthesis is the insertion of a Mg(2+) ion into the tetrapyrrole intermediate
protoporphyrin IX, catalyzed by Mg-chelatase. We have identified a Synechocystis
sp. PCC 6803 strain with a spontaneous mutation in chlH that results in a Gly195
to Glu substitution in a conserved region of the catalytic subunit of Mg
chelatase. Mutant strains containing the ChlH Gly195 to Glu mutation were
generated using a two-step protocol that introduced the chlH gene into a putative
neutral site in the chromosome prior to deletion of the native gene. The Gly195
to Glu mutation resulted in strains with decreased chlorophyll a. Deletion of the
PS II assembly factor Ycf48 in a strain carrying the ChlH Gly195 to Glu mutation
did not grow photoautotrophically. In addition, the ChlH-G195E:DeltaYcf48 strain
showed impaired PS II activity and decreased assembly of PS II centers in
comparison to a DeltaYcf48 strain. We suggest decreased chlorophyll in the ChlH
G195E mutant provides a background to screen for the role of assembly factors
that are not essential under optimal growth conditions.
PMID- 27489556
TI - Alternative Growth and Defensive Strategies Reveal Potential and Gender Specific
Trade-Offs in Dioecious Plants Salix paraplesia to Nutrient Availability.
AB - Population sex ratios of many dioecious plants in nature are biased. This may be
attributed to sexually different resource demands and adaptive capacity. In male
biasedPopulus, males often display stronger physiological adaptation than
females. Interestingly, Populus and Salix, belonging to Salicaceae, display an
opposite biased sex ratio, especially in nutrient-poor environmental conditions.
Do female willows have a greater tolerance to nutrient deficiency than males? In
this study, we investigated the growth and defensive strategies of Salix
paraplesia cuttings, which were grown with high and low soil fertility for about
140 days over one growing season. Results suggest that different strategies for
biomass allocation may result in sexually different defense capacities and trade
offs between growth and defense. Females are likely to adopt radical strategies,
overdrawing on available resources to satisfy both growth and defense, which
seems to be more like a gamble compared with males. It is also suggested that
females may have an extra mechanism to compensate for the investment in growth
under nutrient-poor conditions. In summary, the results may help focus
restoration efforts on sex selection such that a moderate increase in female
willow quantity could increase the resistance and resilience of willow
populations to early sporadic desertification.
PMID- 27489557
TI - Altered Superficial White Matter on Tractography MRI in Alzheimer's Disease.
AB - BACKGROUND/AIMS: Superficial white matter provides extensive cortico-cortical
connections. This tractography study aimed to assess the diffusion
characteristics of superficial white matter tracts in Alzheimer's disease.
METHODS: Diffusion tensor 3T magnetic resonance imaging scans were acquired in 24
controls and 16 participants with Alzheimer's disease. Neuropsychological test
scores were available in some participants. Tractography was performed by the
Fiber Assignment by Continuous Tracking (FACT) method. The superficial white
matter was manually segmented and divided into frontal, parietal, temporal and
occipital lobes. The mean diffusivity (MD), radial diffusivity (RD), axial
diffusivity (AxD) and fractional anisotropy (FA) of these tracts were compared
between controls and participants with Alzheimer's disease and correlated with
available cognitive tests while adjusting for age and white matter hyperintensity
volume. RESULTS: Alzheimer's disease was associated with increased MD (p =
0.0011), increased RD (p = 0.0019) and increased AxD (p = 0.0017) in temporal
superficial white matter. In controls, superficial white matter was associated
with the performance on the Montreal Cognitive Assessment, Stroop and Trail
Making Test B tests, whereas in Alzheimer's disease patients, it was not
associated with the performance on cognitive tests. CONCLUSION: Temporal lobe
superficial white matter appears to be disrupted in Alzheimer's disease.
PMID- 27489558
TI - Does MRI Increase the Diagnostic Confidence of Physicians in an Outpatient Memory
Clinic.
AB - BACKGROUND AND AIM: Data showing the usefulness of MRI to improve the accuracy of
the diagnostic process in cognitive disorders were derived from studies in
tertiary referral centers. MRI is widely used as a diagnostic tool in everyday
practice, but it is unknown what the actual added value of MRI is. We studied the
usefulness of MRI in the diagnostic process by measuring the change of confidence
of the physician. METHODS: Physicians indicated confidence in their diagnosis
before and after presentation of MR images using a visual analogue scale from 0
100%. RESULTS: Use of MRI increased the level of confidence by 3% in experienced
clinicians and by 9% in inexperienced physicians. In 2/125 cases, MRI showed an
unexpected finding. CONCLUSION: MRI is a useful diagnostic tool in everyday
practice of diagnosing cognitive disorders.
PMID- 27489559
TI - Compensatory Postural Adjustments in an Oculus Virtual Reality Environment and
the Risk of Falling in Alzheimer's Disease.
AB - BACKGROUND/AIMS: Alzheimer's disease (AD) patients have an impaired ability to
quickly reweight central sensory dependence in response to unexpected body
perturbations. Herein, we aim to study provoked compensatory postural adjustments
(CPAs) in a conflicting sensory paradigm with unpredictable visual displacements
using virtual reality goggles. METHODS: We used kinematic time-frequency analyses
of two frequency bands: a low-frequency band (LB; 0.3-1.5 Hz; mechanical
strategy) and a high-frequency band (HB; 1.5-3.5 Hz; cognitive strategy). We
enrolled 19 healthy subjects (controls) and 21 AD patients, divided according to
their previous history of falls. RESULTS: The AD faller group presented higher
power LB CPAs, reflecting their worse inherent postural stability. The AD
patients had a time lag in their HB CPA reaction. CONCLUSION: The slower reaction
by CPA in AD may be a reflection of different cognitive resources including body
schema self-perception, visual motion, depth perception, or a different state of
fear and/or anxiety.
PMID- 27489560
TI - Creative Music Therapy in an Acute Care Setting for Older Patients with Delirium
and Dementia.
AB - BACKGROUND/AIMS: The acute hospital ward can be unfamiliar and stressful for
older patients with impaired cognition, rendering them prone to agitation and
resistive to care. Extant literature shows that music therapy can enhance
engagement and mood, thereby ameliorating agitated behaviours. This pilot study
evaluates the impact of a creative music therapy (CMT) programme on mood and
engagement in older patients with delirium and/or dementia (PtDD) in an acute
care setting. We hypothesize that CMT improves engagement and pleasure in these
patients. METHODS: Twenty-five PtDD (age 86.5 +/- 5.7 years, MMSE 6/30 +/- 5.4)
were observed for 90 min (30 min before, 30 min during, and 30 min after music
therapy) on 3 consecutive days: day 1 (control condition without music) and days
2 and 3 (with CMT). Music interventions included music improvisation such as
spontaneous music making and playing familiar songs of patient's choice. The main
outcome measures were mood and engagement assessed with the Menorah Park
Engagement Scale (MPES) and Observed Emotion Rating Scale (OERS). RESULTS:
Wilcoxon signed-rank test showed a statistically significant positive change in
constructive and passive engagement (Z = 3.383, p = 0.01) in MPES and pleasure
and general alertness (Z = 3.188,p = 0.01) in OERS during CMT. The average
pleasure ratings of days 2 and 3 were higher than those of day 1 (Z = 2.466, p =
0.014). Negative engagement (Z = 2.582, p = 0.01) and affect (Z = 2.004, p =
0.045) were both lower during CMT compared to no music. CONCLUSION: These results
suggest that CMT holds much promise to improve mood and engagement of PtDD in an
acute hospital setting. CMT can also be scheduled into the patients' daily
routines or incorporated into other areas of care to increase patient compliance
and cooperation.
PMID- 27489561
TI - Determinants of exclusive breastfeeding practices among mothers in azezo
district, northwest Ethiopia.
AB - BACKGROUND: Exclusive breastfeeding (EBF) is a very important, long lasting and
cost effective intervention to help reduce the morbidity and mortality of
infants. However, a large proportion of infants are not exclusively breastfed as
recommended by the World Health Organization. The study aim was to assess the
exclusive breastfeeding practices and identify determinants among mothers in
Azezo District, Ethiopia. METHODS: A community based cross-sectional study was
conducted among 346 mothers with infants aged between 0-6 months. Data were
collected using a pretested, interviewer administered questionnaire. Descriptive
statistics and logistic regression analysis were used to describe the study
objectives and identify the determinants of EBF in the previous 24 h.
Associations between the study and outcome variables were described using odds
ratios and 95 % confidence intervals (CI). RESULTS: Any breastfeeding and
exclusive breastfeeding in the previous 24 h were 99 and 79 %, respectively. The
mean number of exclusive breastfeeds in the 24 h period was 6.5. Exclusive
breastfeeding rates were highest among mothers aged >= 30 years (Adjusted odds
ratio [AOR] 1.75; 95 % CI 1.14, 3.42). Infants whose mothers were unemployed were
more likely to be exclusively breastfed than infants whose mothers were employed
(AOR 1.62; 95 % CI 1.03, 2.95). Mothers earning <= 1000 birr (US $47.62) monthly
were 77 % less likely to practice EBF (AOR 0.23; 95 % CI 0.13, 0.44). Mothers who
delivered at the healthcare facility practised more exclusive breastfeeding than
those who delivered at home (AOR 2.18; 95 % CI 1.22, 4.35). Mothers who received
antenatal and postnatal care had better rates of EBF (AOR 2.24; 95 % CI 1.18,
5.76 and AOR 1.62; 95 % CI 1.09, 3.21) and mothers not practicing prelacteal
feeding were more likely to exclusively breastfeed compared with mothers
practicing prelacteal feeding (AOR 2.16; 95 % CI 1.16, 4.06). CONCLUSIONS: Any
breastfeeding and exclusive breastfeeding rates in the previous 24 h are
relatively high in the study area compared with previous studies. Maternal
factors (age, education, income, employment, antenatal care, prelacteal feeding),
infants' age, delivery place and information access were independent predictors
to EBF in previous 24 h. Improving the mother's knowledge, income, information
access, nutritional counselling, quality of antenatal and postnatal care service,
place of delivery and avoiding prelacteal feeding practices are important to
improving the exclusive breastfeeding rate in the previous 24 h.
PMID- 27489562
TI - First Report of Familial Juvenile Hyperuricemic Nephropathy (FJHN) in Iran Caused
By a Novel De Novo Mutation (E197X) in UMOD.
AB - Uromodulin (UMOD) gene mutation causes autosomal dominant Uromodulin-Associated
Kidney Disease (UAKD), which in turn leads to end-stage renal disease. This is
the first case report of a family with UAKD caused by a novel de novo mutation
(E197X) in the UMOD gene. This case is a 28-year-old man with severely reduced
kidney function [1]. No similar case was reported in his family history. This
report highlights and reminds the importance of genetic screening in young
patients involving kidney dysfunction, as the UAKD and some other kidney genetic
diseases may be late-onset.
PMID- 27489564
TI - Cancer of the vulva in Burkina Faso: a hospital-based case series.
AB - BACKGROUND: Vulvar cancer is a rare gynaecological cancer. In Burkina Faso, the
diagnosis of vulvar cancers is delayed and the prognosis is poor. However, no
specific study on vulvar cancers has been conducted at the moment. This work
aimed to study the characteristics of these cancers. METHODS: This is a
prospective study on histologically confirmed primary cancers of the vulva
diagnosed between 1st January 2013 and 30th June 2015. The demographic and
clinical aspects were studied at the Yalgado Ouedraogo University Hospital of
Ouagadougou (CHU-YO). RESULTS: We noticed 21 cases of vulvar cancers within 30
months, ranking it as the 4th most common gynaecological cancer. The average age
of the patients was 55 years (standard deviation +/- 6.3) and the median age was
57 years. Scars resulting from female circumcision, menopause (n = 20) and HIV
infection were noticed in 19 cases and 6 cases respectively. The average time
from first symptoms to first consultation was 29 months. Pain and ulceration were
the main reasons for consultation. The clinical picture was chiefly an ulcero
granulating tumour. There was squamous cell carcinoma in 20 cases and basal
carcinoma in 1 case. Fifteen patients were at stage III or IV, where of three
patients had metastatic disease. We noticed vitiligo in 9 vulvar cancer cases.
CONCLUSION: The cancer of the vulva is rare. Women are of menopausal age, are
mostly circumcised and HIV-infection is common. A majority of patients sought
consultation at advanced stage of disease, and diagnosis was belatedly made. Pain
and ulceration were the main reasons for consultation. The sensitization of the
population, education for self- examination would allow earlier diagnosis.
PMID- 27489563
TI - An ABCD1 Mutation (c.253dupC) Caused Diverse Phenotypes of Adrenoleukodystrophy
in an Iranian Consanguineous Pedigree.
AB - OBJECTIVES: Current study was the first to report a consanguineous Iranian
pedigree with ABCD1 mutation. METHODS: Targeted molecular analysis was initially
performed in three affected individuals in one family suspected to have X-ALD due
to chronic progressive spasticity. Upon confirmation of genetic diagnosis,
further neurologic and genetic evaluation of all family members was done.
RESULTS: A mutation in ABCD1 was identified in 35 affected individuals (out 96
pedigree members). The c. 253dup, in exon 1, leads to a frame shift and a
premature stop codon at amino acid position 194 (p.Arg85Profs*110). Surprisingly,
affected individuals in our cohort show some variability in phenotype, including
childhood cerebral ALD, adrenomyeloneuropathy, and addison-only disease
phenotypes, expanding the phenotype of X-ALD with p.Arg85Profs*110. CONCLUSION:
This report characterizes the clinical spectrum of an expanded Iranian pedigree
with X-ALD due to an ABCD1 mutation. Given a high frequency of carriers in this
region, we expect the prevalence of X-ALD to be higher, underscoring the
importance of genetic counseling through reliable identification of heterozygous
as well as homozygote females in consanguineous communities.
PMID- 27489565
TI - Mental health problems among conflict-affected adults in Grozny, Chechnya: a
qualitative study.
AB - BACKGROUND: A decade of conflict in Chechnya destroyed infrastructure and
resulted in widespread exposure to violence. Amidst substantial reconstruction,
periodic violence has contributed to an ongoing atmosphere of insecurity. We
conducted a qualitative study to understand the mental health and psychosocial
problems affecting adult Chechens in this context to inform development of
assessment tools for an evaluation study related to individual counseling.
METHODS: Data were collected in July 2014. A convenience sample of 59 Chechen
adults was asked to Free List all problems affecting people in the area. Four
problems were explored further in 19 Key Interviewee (KI) interviews, with
respondents identified using snowball sampling. Data analysis was conducted in
Russian by the Chechen interviewers. RESULTS: Multiple mental health and
psychosocial problems emerged, including 'bad psychological health',
'depression', 'stress and nervous people', and 'problems in the family'.
Aggression, 'emotional blowing', and 'not adequate' behavior were frequently
reported indicators of these problems, with negative effects on the whole family.
Chechens reported seeking help through informal social networks, psychiatric and
psychological services, and Islamic Centers. CONCLUSION: Chechens reported mental
health and psychosocial problems similar to those experienced in other post
conflict settings. The description of 'emotional blowing' mirrored prior findings
in Chechen asylum seekers and fits within a cluster of cultural concepts of
distress featuring anger that has been identified in other conflict-affected
populations. Further exploration of the nature and prevalence of this construct,
as well as evaluations of interventions aimed at reducing these symptoms, is
warranted.
PMID- 27489566
TI - Sustainable bioenergy production with little carbon debt in the Loess Plateau of
China.
AB - BACKGROUND: As a key strategy for mitigating global climate change, bioenergy
production by reducing CO2 emissions plays an important role in ensuring
sustainable development. However, land-use change by converting natural
ecosystems into energy crop field could create a carbon debt at the beginning.
Thus, the potential carbon debt calculation is necessary for determining a
promising bioenergy crop production, especially in the region rich of marginal
land. RESULTS: Here, we used high-resolution historical land-use data to identify
the marginal land available and to evaluate the carbon debt of planting
Miscanthus in the Loess Plateau, China. We found that there were 27.6 Mha for
energy production and 9.7 Mha for ecological restoration, with total annual
production of 0.41 billion tons of biomass. We also found that soil carbon
sequestration and total CO2 mitigation were 9.3 Mt C year(-1) and 542 Mt year(
1), respectively. More importantly, the result showed that planting Miscanthus on
marginal land in the Loess Plateau only took 0.97 years on average to repay the
carbon debt. CONCLUSIONS: Our study demonstrated that Miscanthus production in
suitable marginal land in the Loess Plateau can offer considerable renewable
energy and mitigate climate change with little carbon debt. These results
suggested that bioenergy production in the similar arid and semiarid region
worldwide would contribute to carbon sequestration in the context of rapid
climate change.
PMID- 27489567
TI - Multiple syntrophic interactions drive biohythane production from waste sludge in
microbial electrolysis cells.
AB - BACKGROUND: Biohythane is a new and high-value transportation fuel present as a
mixture of biomethane and biohydrogen. It has been produced from different
organic matters using anaerobic digestion. Bioenergy can be recovered from waste
activated sludge through methane production during anaerobic digestion, but
energy yield is often insufficient to sludge disposal. Microbial electrolysis
cell (MEC) is also a promising approach for bioenergy recovery and waste sludge
disposal as higher energy efficiency and biogas production. The systematic
understanding of microbial interactions and biohythane production in MEC is still
limited. Here, we report biohythane production from waste sludge in biocathode
microbial electrolysis cells and reveal syntrophic interactions in microbial
communities based on high-throughput sequencing and quantitative PCR targeting
16S rRNA gene. RESULTS: The alkali-pretreated sludge fed MECs (AS-MEC) showed the
highest biohythane production rate of 0.148 L.L(-1)-reactor.day(-1), which is 40
and 80 % higher than raw sludge fed MECs (RS-MEC) and anaerobic digestion (open
circuit MEC, RS-OCMEC). Current density, metabolite profiles, and hydrogen
methane ratio results all confirm that alkali-pretreatment and microbial
electrolysis greatly enhanced sludge hydrolysis and biohythane production.
Illumina Miseq sequencing of 16S rRNA gene amplicons indicates that anode biofilm
was dominated by exoelectrogenic Geobacter, fermentative bacteria and hydrogen
producing bacteria in the AS-MEC. The cathode biofilm was dominated by
fermentative Clostridium. The dominant archaeal populations on the cathodes of AS
MEC and RS-MEC were affiliated with hydrogenotrophic Methanobacterium (98 %,
relative abundance) and Methanocorpusculum (77 %), respectively. Multiple
pathways of gas production were observed in the same MEC reactor, including
fermentative and electrolytic H2 production, as well as hydrogenotrophic
methanogenesis and electromethanogenesis. Real-time quantitative PCR analyses
showed that higher amount of methanogens were enriched in AS-MEC than that in RS
MEC and RS-OCMEC, suggesting that alkali-pretreated sludge and MEC facilitated
hydrogenotrophic methanogen enrichment. CONCLUSION: This study proves for the
first time that biohythane could be produced directly in biocathode MECs using
waste sludge. MEC and alkali-pretreatment accelerated enrichment of
hydrogenotrophic methanogen and hydrolysis of waste sludge. The results indicate
syntrophic interactions among fermentative bacteria, exoelectrogenic bacteria and
methanogenic archaea in MECs are critical for highly efficient conversion of
complex organics into biohythane, demonstrating that MECs can be more competitive
than conventional anaerobic digestion for biohythane production using
carbohydrate-deficient substrates. Biohythane production from waste sludge by MEC
provides a promising new way for practical application of microbial
electrochemical technology.
PMID- 27489568
TI - The ancestral chromosomes of Dromiciops gliroides (Microbiotheridae), and its
bearings on the karyotypic evolution of American marsupials.
AB - BACKGROUND: The low-numbered 14-chromosome karyotype of marsupials has falsified
the fusion hypothesis claiming ancestrality from a 22-chromosome karyotype. Since
the 14-chromosome condition of the relict Dromiciops gliroides is reminecent of
ancestrality, its interstitial traces of past putative fusions and
heterochromatin banding patterns were studied and added to available marsupials'
cytogenetic data. Fluorescent in situ hybridization (FISH) and self-genomic in
situ hybridization (self-GISH) were used to detect telomeric and repetitive
sequences, respectively. These were complemented with C-, fluorescent banding,
and centromere immunodetection over mitotic spreads. The presence of interstitial
telomeric sequences (ITS) and diploid numbers were reconstructed and mapped onto
the marsupial phylogenetic tree. RESULTS: No interstitial, fluorescent signals,
but clearly stained telomeric regions were detected by FISH and self-GISH.
Heterochromatin distribution was sparse in the telomeric/subtelomeric regions of
large submetacentric chromosomes. Large AT-rich blocks were detected in the long
arm of four submetacentrics and CG-rich block in the telomeric regions of all
chromosomes. The ancestral reconstructions both ITS presence and diploid numbers
suggested that ITS are unrelated to fusion events. CONCLUSION: Although the lack
of interstitial signals in D. gliroides' karyotype does not prove absence of past
fusions, our data suggests its non-rearranged plesiomorphic condition.
PMID- 27489569
TI - Mango: combining and analyzing heterogeneous biological networks.
AB - BACKGROUND: Heterogeneous biological data such as sequence matches, gene
expression correlations, protein-protein interactions, and biochemical pathways
can be merged and analyzed via graphs, or networks. Existing software for network
analysis has limited scalability to large data sets or is only accessible to
software developers as libraries. In addition, the polymorphic nature of the data
sets requires a more standardized method for integration and exploration.
RESULTS: Mango facilitates large network analyses with its Graph Exploration
Language, automatic graph attribute handling, and real-time 3-dimensional
visualization. On a personal computer Mango can load, merge, and analyze networks
with millions of links and can connect to online databases to fetch and merge
biological pathways. CONCLUSIONS: Mango is written in C++ and runs on Mac OS,
Windows, and Linux. The stand-alone distributions, including the Graph
Exploration Language integrated development environment, are freely available for
download from http://www.complex.iastate.edu/download/Mango. The Mango User Guide
listing all features can be found at http://www.gitbook.com/book/j23414/mango
user-guide.
PMID- 27489570
TI - Pinpointing the vesper bat transposon revolution using the Miniopterus natalensis
genome.
AB - BACKGROUND: Around 40 million years ago DNA transposons began accumulating in an
ancestor of bats in the family Vespertilionidae. Since that time, Class II
transposons have been continuously reinvading and accumulating in vespertilionid
genomes at a rate that is unprecedented in mammals. Miniopterus (Miniopteridae),
a genus of long-fingered bats that was recently elevated from Vespertilionidae,
is the sister taxon to the vespertilionids and is often used as an outgroup when
studying transposable elements in vesper bats. Previous wet-lab techniques failed
to identify Helitrons, TcMariners, or hAT transposons in Miniopterus. Limitations
of those methods and ambiguous results regarding the distribution of piggyBac
transposons left some questions as to the distribution of Class II elements in
this group. The recent release of the Miniopterus natalensis genome allows for
transposable element discovery with a higher degree of precision. RESULTS: Here
we analyze the transposable element content of M. natalensis to pinpoint with
greater accuracy the taxonomic distribution of Class II transposable elements in
bats. These efforts demonstrate that, compared to the vespertilionids, Class II
TEs are highly mutated and comprise only a small portion of the M. natalensis
genome. Despite the limited Class II content, M. natalensis possesses a limited
number of lineage-specific, low copy number piggyBacs and shares several
TcMariner families with vespertilionid bats. Multiple efforts to identify
Helitrons, one of the major TE components of vesper bat genomes, using de novo
repeat identification and structural based searches failed. CONCLUSIONS: These
observations combined with previous results inform our understanding of the
events leading to the unique Class II element acquisition that characterizes
vespertilionids. While it appears that a small number of TcMariner and piggyBac
elements were deposited in the ancestral Miniopterus + vespertilionid genome,
these elements are not present in M. natalensis genome at high copy number.
Instead, this work indicates that the vesper bats alone experienced the expansion
of TEs ranging from Helitrons to piggyBacs to hATs.
PMID- 27489571
TI - Hip dysplasia screening - epidemiological data from Valcea County.
AB - RATIONALE: :In its most severe form, developmental dysplasia of the hip (DDH) is
one of the most common congenital malformations. Uncorrected developmental
dysplasia of the hip is associated with long-term morbidity such as gait
abnormalities, chronic pain, and degenerative arthritis. AIMS: (1) to identify
the risks and predisposing factors involved in DDH (2) to define the incidence of
the disease locally; (3) to emphasize the importance of ultrasonography in early
diagnosis of DDH. METHODS AND RESULTS: 1021 newborns in the Neonatal Department
of Valcea County Emergency Hospital were analyzed. The information contained in
the observation sheets was collected and upon this, the ultrasound was performed
accordingly to Graf's classification. The following parameters were analyzed:
sex, area of origin, gestational age, birthweight, type of delivery, parturition.
Out of 1021 newborns, 27 had an abnormal ultrasound examination. 20 infants were
diagnosed with DDH. Regarding the risk factors: cephalic delivery was associated
with a lower risk/ the lowest of DDH (with p=0.045 for the right hip and p=0.001
for the left hip). Increased gestational age and increased birthweight were
incriminating factors in the occurrence of DDH. DISCUSSION: Ultrasound imaging
has become an accepted tool for accurately diagnosing DDH.
PMID- 27489572
TI - Psychometric Validation of the Revised Family Affluence Scale: a Latent Variable
Approach.
AB - The aim was to develop and test a brief revised version of the family affluence
scale. A total of 7120 students from Denmark, Greenland, Italy, Norway, Poland,
Romania, Scotland and Slovakia reported on a list of 16 potential indicators of
affluence. Responses were subject to item screening and test of dimensionality.
Bifactor analysis revealed a strong general factor of affluence in all countries,
but with additional specific factors in all countries. The specific factors
mainly reflected overlapping item content. Item screening was conducted to
eliminate items with low discrimination and local dependence, reducing the number
of items from sixteen to six: Number of computers, number of cars, own bedroom,
holidays abroad, dishwasher, and bathroom. The six-item version was estimated
with Samejima's graded response model, and tested for differential item
functioning by country. Three of the six items were invariant across countries,
thus anchoring the scale to a common metric across countries. The six-item scale
correlated with parental reported income groups in six out of eight countries.
Findings support a revision to six items in the family affluence scale.
PMID- 27489573
TI - Trends in Child Poverty in Sweden: Parental and Child Reports.
AB - We use several family-based indicators of household poverty as well as child
reported economic resources and problems to unravel child poverty trends in
Sweden. Our results show that absolute (bread-line) household income poverty, as
well as economic deprivation, increased with the recession 1991-96, then reduced
and has remained largely unchanged since 2006. Relative income poverty has
however increased since the mid-1990s. When we measure child poverty by young
people's own reports, we find few trends between 2000 and 2011. The material
conditions appear to have improved and relative poverty has changed very little
if at all, contrasting the development of household relative poverty. This
contradictory pattern may be a consequence of poor parents distributing
relatively more of the household income to their children in times of economic
duress, but future studies should scrutinze potentially delayed negative
consequences as poor children are lagging behind their non-poor peers. Our
methodological conclusion is that although parental and child reports are partly
substitutable, they are also complementary, and the simultaneous reporting of
different measures is crucial to get a full understanding of trends in child
poverty.
PMID- 27489575
TI - The initiation of post-synaptic protrusions.
AB - The post-synaptic spines of neuronal dendrites are highly elaborate membrane
protrusions. Their anatomy, stability and density are intimately linked to
cognitive performance. The morphological transitions of spines are powered by
coordinated polymerization of actin filaments against the plasma membrane, but
how the membrane-associated polymerization is spatially and temporally regulated
has remained ill defined. Here, we discuss our recent findings showing that
dendritic spines can be initiated by direct membrane bending by the I-BAR protein
MIM/Mtss1. This lipid phosphatidylinositol (PI(4,5)P2) signaling-activated
membrane bending coordinated spatial actin assembly and promoted spine formation.
From recent advances, we formulate a general model to discuss how spatially
concentrated protein-lipid microdomains formed by multivalent interactions
between lipids and actin/membrane regulatory proteins might launch cell
protrusions.
PMID- 27489574
TI - Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome
relationships reflect adverse effects?
AB - Several reports describe U-shaped 25-hydroxyvitamin D [25(OH)D] concentration
health outcomes, including musculo-skeletal disorders such as falls and
fractures, several cancers, cardiovascular disease (CVD), cognitive function, all
cause mortality rates, birth outcomes, allergic reactions, frailty, and some
other disorders. This paper reviews reports of U-shaped outcome associations with
vitamin D status for evidence of underlying pathophysiological processes, or of
confounding, finding that some U-shaped associations appear to be biologically
meaningful, but that many could well reflect confounding by factors such as
lifestyle, or hypovitaminosis D-related disease onset being masked by self
supplementation that was begun too late to correct developing health problems but
before baseline vitamin D status assessment. However, the various U-shaped
associations for allergic reactions may be due to vitamin D modulation of the
phenotype of the immune response, shifting the Th1-Th2 balance toward Th2
formation. For prostate cancer, there seems to be little effect of 25(OH)D
concentration on incidence; however, there is an inverse correlation between
25(OH)D concentration and mortality rates. Future observational studies, and
randomized controlled trial data analyses, should include adjustment for data
collected on prior long-term vitamin D supplementation and solar UVB exposure, as
well as other potential confounders.
PMID- 27489576
TI - Fundamental awareness: A framework for integrating science, philosophy and
metaphysics.
AB - The ontologic framework of Fundamental Awareness proposed here assumes that non
dual Awareness is foundational to the universe, not arising from the interactions
or structures of higher level phenomena. The framework allows comparison and
integration of views from the three investigative domains concerned with
understanding the nature of consciousness: science, philosophy, and metaphysics.
In this framework, Awareness is the underlying reality, not reducible to anything
else. Awareness and existence are the same. As such, the universe is non
material, self-organizing throughout, a holarchy of complementary, process
driven, recursive interactions. The universe is both its own first observer and
subject. Considering the world to be non-material and comprised, a priori, of
Awareness is to privilege information over materiality, action over agency and to
understand that qualia are not a "hard problem," but the foundational elements of
all existence. These views fully reflect main stream Western philosophical
traditions, insights from culturally diverse contemplative and mystical
traditions, and are in keeping with current scientific thinking, expressible
mathematically.
PMID- 27489578
TI - An exploration of how to define and measure the evolution of behavior, learning,
memory and mind across the full phylogenetic tree of life.
AB - There are probably few terms in evolutionary studies regarding neuroscience
issues that are used more frequently than 'behavior', 'learning', 'memory', and
'mind'. Yet there are probably as many different meanings of these terms as there
are users of them. Further, investigators in such studies, while recognizing the
full phylogenetic spectrum of life and the evolution of these phenomena, rarely
go beyond mammals and other vertebrates in their investigations; invertebrates
are sometimes included. What is rarely taken into consideration, though, is that
to fully understand the evolution and significance for survival of these
phenomena across phylogeny, it is essential that they be measured and compared in
the same units of measurement across the full phylogenetic spectrum from aneural
bacteria and protozoa to humans. This paper explores how these terms are
generally used as well as how they might be operationally defined and measured to
facilitate uniform examination and comparisons across the full phylogenetic
spectrum of life. This paper has 2 goals: (1) to provide models for measuring the
evolution of 'behavior' and its changes across the full phylogenetic spectrum,
and (2) to explain why 'mind phenomena' cannot be measured scientifically at the
present time.
PMID- 27489577
TI - Inter-organelle ER-endolysosomal contact sites in metabolism and disease across
evolution.
AB - Since their initial observation, contact sites formed between different
organelles have transitioned from ignored curiosities to recognized centers for
the exchange of metabolites and lipids. Contact formed between the ER and
endomembrane system (eg. the plasma membrane, endosomes, and lysosomes) is of
particular biomedical interest, as it governs aspects of lipid metabolism,
organelle identity, and cell signaling. Here, we review the field of ER
endolysosomal communication from the perspective of three model systems: budding
yeast, the fruit fly D. melanogaster, and mammals. From this broad perspective,
inter-organelle communication displays a consistent role in metabolic regulation
that was differentially tuned during the development of complex metazoan life. We
also examine the current state of understanding of lipid exchange between
organelles, and discuss molecular mechanisms by which this occurs.
PMID- 27489579
TI - Life and evolution as physics.
AB - What is evolution and why does it exist in the biological, geophysical and
technological realms - in short, everywhere? Why is there a time direction - a
time arrow - in the changes we know are happening every moment and everywhere?
Why is the present different than the past? These are questions of physics, about
everything, not just biology. The answer is that nothing lives, flows and moves
unless it is driven by power. Physics sheds light on the natural engines that
produce the power destroyed by the flows, and on the free morphing that leads to
flow architectures naturally and universally. There is a unifying tendency across
all domains to evolve into flow configurations that provide greater access for
movement. This tendency is expressed as the constructal law of evolutionary flow
organization everywhere. Here I illustrate how this law of physics accounts for
and unites the life and evolution phenomena throughout nature, animate and
inanimate.
PMID- 27489581
TI - Anxiety and ritualization: Can attention discriminate compulsion from routine?
AB - Despite the wide occurrence of ritual behavior in humans and animals, much of its
causal underpinnings, as well as evolutionary functions, remain unknown. A
prominent line of research focuses on ritualization as a response to anxiogenic
stimuli. By manipulating anxiety levels, and subsequently assessing their motor
behavior dynamics, our recent study investigated this causal link in a controlled
way. As an extension to our original argument, we here discuss 2 theoretical
explanations of rituals-ritualized behavior and automated behavior-and their link
to anxiety. We propose that investigating participant's locus of attention can
discriminate between these 2 models.
PMID- 27489580
TI - Deciphering the roles of phosphoinositide lipids in phagolysosome biogenesis.
AB - Professional phagocytes engulf microbial invaders into plasma membrane-derived
phagosomes. These mature into microbicidal phagolysosomes, leading to killing of
the ingested microbe. Phagosome maturation involves sequential fusion of the
phagosome with early endosomes, late endosomes, and the main degradative
compartments in cells, lysosomes. Some bacterial pathogens manipulate the
phosphoinositide (PIP) composition of phagosome membranes and are not delivered
to phagolysosomes, pointing at a role of PIPs in phagosome maturation. This
hypothesis is supported by comprehensive microscopic studies. Recently, cell-free
reconstitution of fusion between phagosomes and endo(lyso)somes identified
phosphatidylinositol 4-phosphate [PI(4)P] and phosphatidylinositol 3-phosphate
[PI(3)P] as key regulators of phagolysosome biogenesis. Here, we describe the
emerging roles of PIPs in phagosome maturation and we present tools to study PIP
involvement in phagosome trafficking using intact cells or purified compartments.
PMID- 27489582
TI - Similar requirement for clathrin in EGF- and HGF- stimulated Akt phosphorylation.
AB - Receptor tyrosine kinases, such as the epidermal growth factor (EGF) receptor
(EGFR) and Met lead to activation of intracellular signals including Akt, a
critical regulator of cell survival, metabolism and proliferation. Upon binding
their respective ligands, each of these receptors is recruited into clathrin
coated pits (CCPs) eventually leading to endocytosis. We have recently shown that
phosphorylation of Gab1 and Akt following EGFR activation requires clathrin, but
does not require receptor endocytosis. We examined whether clathrin regulates Akt
signaling downstream of Met, as it does for EGFR signaling. Stimulation with the
Met ligand Hepatocyte Growth Factor (HGF) leads to enrichment of phosphorylated
Gab1 (pGab1) within CCPs in ARPE-19 cells. Perturbation of clathrin using the
inhibitor pitstop2 decreases HGF-stimulated Akt phosphorylation. These results
indicate that clathrin may regulate Met signaling leading to Akt phosphorylation
similarly as it does for EGFR signaling.
PMID- 27489583
TI - Glycosylation of arabinogalactan-proteins essential for development in
Arabidopsis.
AB - Arabinogalactan-proteins (AGPs) are ubiquitous cell wall components present
throughout the plant kingdom. They are extensively post translationally modified
by conversion of proline to hydroxyproline (Hyp) and by addition of
arabinogalactan (AG) polysaccharides to Hyp residues. Two small gene subfamilies
within the CAZy GT31 family, referred to as Hyp-galactosyltransferases (Hyp-GALTs
and HPGTs), encode enzymes that specifically add galactose to AGP protein
backbones as revealed by heterologous expression of the genes coupled with an in
vitro enzyme assay and by biochemical characterization of the genetic knock-out
mutants. Biochemical analysis of galt2galt5 double and hpgt1hpgt2hpgt3 triple
knockout mutants revealed significant reductions in both AGP-specific Hyp-GALT
activity and beta-Gal-Yariv precipitable AGPs. Further analysis of these mutants
demonstrated both overlapping and distinct pleiotropic growth and development
phenotypes, indicating the important contributions of the carbohydrate moieties
toward AGP function. Current research indicates that all 8 Hyp-GALT/HPGT genes
encode enzymes that catalyze the initial step for AGP glycosylation and that AGP
glycans play essential roles in plant growth and development.
PMID- 27489584
TI - Mechanical defenses of plant extrafloral nectaries against herbivory.
AB - Extrafloral nectaries play an important role in plant defense against herbivores
by providing nectar rewards that attract ants and other carnivorous insects.
However, extrafloral nectaries can themselves be targets of herbivory, in
addition to being exploited by nectar-robbing insects that do not provide
defensive services. We recently found that the extrafloral nectaries of Vicia
faba plants, as well as immediately adjacent tissues, exhibit high concentrations
of chemical toxins, apparently as a defense against herbivory. Here we report
that the nectary tissues of this plant also exhibit high levels of structural
stiffness compared to surrounding tissues, likely due to cell wall lignification
and the concentration of calcium oxalate crystals in nectary tissues, which may
provide an additional deterrent to herbivore feeding on nectary tissues.
PMID- 27489585
TI - Demonstrating the value of medicines: evolution of value equation and stakeholder
perception of uncertainties.
AB - It is important to evaluate how the value of medicine is assessed, as it may have
important implications for health technology and reimbursement assessments. The
value equation could comprise 'incremental benefit/outcome' (relative results of
care in terms of patient health, comparing the innovation to best available
alternative(s)) in the numerator and 'cost' (relative costs involved in the full
cycle of care (or a defined period) for the patient's medical condition,
incorporating the relevant cost-offsets due to displacement of best available
alternative(s)) in the denominator. This 'relative value' combined with the
overall net budget impact (of including the drug in the formulary or reimbursed
drug list) at the concerned population level in the given
institution/region/country may better inform the usefulness of the new
therapeutic option to the healthcare system. As product value messages are
created, anticipating external stakeholder questions and information needs,
including addressing three main categories of 'uncertainties', namely the
scientific uncertainties, usage uncertainties, and financial uncertainties, could
facilitate demonstration of optimal product value and help informed decision
making to benefit all stakeholders involved in the process.
PMID- 27489586
TI - Challenges in striving to simultaneously achieve multiple resource allocation
goals: the pan-Canadian Oncology Drug Review (pCODR) example.
AB - The pan-Canadian Oncology Drug Review (pCODR) makes recommendations to Canada's
provinces and territories (except Quebec) to guide their cancer drug funding
decisions. The objective of this paper is to explore, using an economic
perspective and the pCODR as an example, the challenges associated with striving
to simultaneously achieve the goals of maximizing health benefits with available
resources and improving access to a more consistent standard of care across
Canada. The first challenge concerns how to interpret the goals in order to
determine how resources should be allocated to achieve each goal. The second
challenge relates to whether, if pursued simultaneously, both goals can be
achieved to the same extent that each goal could have been achieved alone with
the same available resources. Regarding the first challenge, we illustrate that,
due to a lack of definitional clarity, it is difficult to determine exactly how
resources should be allocated in order to achieve the goal of improving access to
a more consistent standard of care across Canada. Regarding the second challenge,
we illustrate that choosing to strive for both of the pCODR goals simultaneously
will likely be associated with tradeoffs in the extent to which one or both goals
can be achieved (relative to what could have been achieved for each goal alone
with the same available resources). We suggest that, if the pCODR and the
provincial drug plan decision-makers it supports want to strive for both goals
simultaneously, they must prioritize the goals and explicitly identify the
tradeoffs associated with the prioritization. This will ensure that the
consequences of striving to simultaneously achieve both goals are explicit,
transparent, and predictable for provincial drug plan decision-makers,
physicians, patients, caregivers, and society as a whole.
PMID- 27489587
TI - Curcumin Veto the Effects of Osteopontin (OPN) Specific Inhibitor on Leukemic
Stem Cell Colony Forming Potential via Promotion of OPN Overexpression.
AB - BACKGROUND: Acute myeloid leukemia (AML) is an immunophenotypically heterogeneous
malignant disease, in which CD34 positivity is associated with poor prognosis.
Osteopontin (OPN) plays different roles in physiologic and pathologic conditions
like: survival, metastasis and cell protection from cytotoxic and apoptotic
stimuli. Due to anti-apoptotic effect of OPN in normal and malignant cells,
silencing of OPN leads to elevation of sensitivity towards chemotherapeutic
agents and attenuates cancer cells migration and invasion. Therefore, the aim of
this study was to evaluate OPN roles in modulating curcumin-mediated growth
inhibitory on leukemic stem cells (LSCs) colony forming potential and survival in
AML cell lines and primary CD34+/CD38- bone marrow-derived AML cells. MATERIALS
AND METHODS: Primary human CD34+/CD38- cells were isolated from bone marrow
mononuclear cells of 10 AML patients at initial state of diagnosis, using a CD34
Multi sort kit. The growth inhibitory effects of curcumin (CUR) were evaluated by
MTT and colony-formation assays. Apoptosis was analyzed by 7AAD assay in CD34+ KG
1, U937 cell lines and primary isolated cells. Short interfering RNA (siRNA)
against OPN was used for OPN silencing in both cell lines and primary AML cells.
Then, transfected cells were incubated with/without curcumin. The change in OPN
gene expression was examined by Real-time PCR. RESULTS: CUR inhibited
proliferation and induced apoptosis in both KG-1 and U937 cells and also primary
isolated AML cells. OPN silencing by siRNA increased the susceptibility of KG-1,
U937 and primary CD34+/CD38- AML cells to apoptosis. Moreover, soft agar colony
assays revealed that silencing of OPN with siRNA significantly decreased colony
numbers in LSCs compared with the non-targeting group. Furthermore, CD34+/CD38-
populations as a main LSCs compartment through OPN overexpression towards CUR
treatment might be nullified the inhibitory effects of OPN siRNA on their
survival and colony forming potential. CONCLUSION: Taken together, our results
suggested that knockdown of OPN using OPN specific siRNA significantly decreased
colony numbers in LSCs and this effect might be vetoed by LSCs via induction of
OPN overexpressionin combination of CUR and siRNA.
PMID- 27489588
TI - Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene
Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an
Iranian Population.
AB - BACKGROUND: The present study was aimed to examine the possible association
between methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms and
childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population.
SUBJECTS AND METHODS: A total of 220 subjects including 100 children diagnosed
with ALL and 120 healthy children participated in the case-control study. The
single nucleotide polymorphisms (SNPs) of MTHFR were determined by ARMS-PCR or
PCR-RFLP method. RESULTS: Our investigation revealed that rs13306561 both TC and
TC + CC genotypes decreased the risk of ALL compared to TT genotype (OR=0.32,
95%CI=0.15-0.68, p=0.002 and OR=0.35, 95%CI=0.17-0.70, p=0.003, respectively). In
addition, the rs13306561 C allele decreased the risk of ALL in comparison with T
allele (OR=0.42, 95% CI=0.22-0.78, P=0.005). MTHFR rs1801131 (A1298C)
polymorphism showed that the AC heterozygous genotype decreased the risk of ALL
in comparison with AA homozygous genotype (OR=0.43, 95%CI=0.21-0.90, p=0.037).
Neither the overall Chi-square comparison of cases and control subjects
(??2=5.54, p=0.063) nor the logistic regression analysis showed significant
association between C677T polymorphism and ALL (OR=1.25, 95% CI=0.69-2.23,
p=0.552; CT vs. CC). CONCLUSION: The current investigation findings showed that
MTHFR rs1801131 and rs13306561 polymorphisms decreased the risk of ALL in the
population which has been studied. Further studies with larger sample sizes and
different ethnicities are required to validate our findings.
PMID- 27489589
TI - Diagnosis and Classification of Acute Leukemia in Bone Marrow Trephine Biopsies,
Utility of a Selected Panel of Minimal Immunohistochemical Markers.
AB - BACKGROUND: Acute leukemias are characterized by neoplastic proliferation of
hematopoietic stem cells and accumulation of blasts and immature cells in bone
marrow. We applied a selective panel of immunohistochemical markers on bone
marrow trephine tissue sections and observed their utility in diagnosis and
typing of acute leukemia. MATERIALS AND METHODS: The study was done at PSG
Institute of Medical Sciences and Research from 1st January, 2008 to 30th June,
2012. Immunohistochemistry was done to detect the expression of Myeloperoxidase
(MPO), Terminal deoxynucleotidyl transferase (TdT), Cluster of Differentiation 3
(CD3) and Cluster of Differentiation 20 (CD20). RESULTS: On an average, 76 new
cases of leukemia are diagnosed each year in our hospital. Of these 28.7% are
acute leukemias, which had a bimodal peak age of occurrence with almost equal sex
distribution. Only 9 cases could be typed as Acute Myeloid Leukemia (AML) or
Acute Lymphoid Leukemia (ALL) purely by morphology. Another 10 cases were typed
using cytochemistry. Immunohistochemical panel helped to type 90% of cases. We
also identified 1 case of AML of ambiguous lineage. The data were analysed
statistically using SPSS version 21 and found out that the immunohistochemistry
was found to be extremely significant (p<001) by Chi-Square test. CONCLUSIONS:
Based on our results, we suggest the use of this limited panel of markers for
routine evaluation of all acute leukemias. It is easier to type using
immunohistochemistry rather than flow cytometry, given the disadvantage of the
costs involved with the latter.
PMID- 27489590
TI - Evaluation of Minimal Residual Disease in Acute Myeloid Leukemia with NPM1
Marker.
AB - BACKGROUND: Minimal residual disease (MRD) tests provide early identification of
hematologic relapse and timely management of acute myeloid leukemia (AML)
patients. Approximately, 50% of AML patients do not have clonal chromosomal
aberrations and categorize as a cytogenetically normal acute myeloid leukemia (CN
AML). About 60% of adult CN-AML has a mutation in exon 12 of NPM1 gene. This
mutation is specific for malignant clone and potentially is a good marker of MRD.
In this retrospective study, we set up a quantitative test for quantifying NPM1
type A mutation and AML patients carrying this mutation at the time of diagnosis,
were followed-up. Materials and Methods : We prepared plasmids containing a cDNA
fragment of NPM1 and ABL genes by PCR cloning. The plasmids were used to
construct standard curves. Eleven patients were analyzed using established
method. Serial PB and/or BM samples (n=71) were taken in 1-3 months intervals
(mean 1.5-month intervals) and median follow-up duration after chemotherapy was
11 months (5-28.5 months). RESULTS: In this study, we developed RNA-based RQ-PCR
to quantitation of NPM1 mutation A with sensitivities of 10((-5)). The percent of
NPMmut/ABL level showed a range between 132 and 757 with median of 383.5 in
samples at diagnosis. The median NPMmut transcript level log reduction was 3
logs. Relapse occurred in 54.5% of patients (n=6), all cases at diagnosis
demonstrated the same mutation at relapse. In patients who experienced relapse,
log reduction levels of NPM1 mRNA transcript after therapy were 4 (n=2), 3 (n=2)
and 1 log (n=2). Totally, NPMmut level showed less than 5 log reduction in all of
them, whereas this reduction was 5-6 logs in other patients. CONCLUSION: Despite
the limitations of this study in terms of sample size and duration of follow-up,
it showed the accuracy of set up for detection of mutation and this marker has
worth for following-up at different stages of disease. Because of high frequency,
stability, specificity to abnormal clone and high sensitivity, NPM1 is a suitable
marker for monitoring of NPMc+ AML patients.
PMID- 27489591
TI - Evaluation of Bone Mineral Density in Children with Acute Lymphoblastic Leukemia
(ALL) and Non-Hodgkin's Lymphoma (NHL): Chemotherapy with/without Radiotherapy.
AB - BACKGROUND: Acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL)
are the most common malignancies in children and adolescents. Therapies such as
corticosteroids, cytotoxic and radiotherapy will have harmful effect on bone
mineral density (BMD) which can lead to increased possibility of osteoporosis and
pathological fractures. SUBJECTS AND METHODS: This 3-year cross-sectional study
was performed in 50 children with ALL (n=25) and NHL (n=25) at Dr. Sheikh
Children's Hospital in Mashhad. Half the patients received chemotherapy alone
(n=25), while the other half received chemotherapy plus radiotherapy (n=25). We
assessed them in the remission phase by DEXA bone mineral densitometry at the
lumbar spine and femoral neck (hip). The survey results were adjusted in
accordance with age, height, sex and Body Mass Index. Results : The mean age was
3.93+/- 8.28 years. There was no significant difference in bone biomarkers (Ca,
P, ALP, PTH) among ALL, NHL and also the two treatment groups. Children with ALL
had lower density at the hip and lumbar spine (p-value<0.001 and p-value=0.018,
respectively). Among the total of 50 patients, 3 patients had normal results for
detected hip BMD (6%), while 14 (28%) had osteopenia and 33 had osteoporosis
(66%). Only one patient had normal BMD among all the patients who received
chemotherapy plus radiotherapy, whereas 2 patients had normal BMD with just
chemotherapy treatment. Conclusion : Given that 94% of our patients had abnormal
bone density, it seems to be crucial to pay more attention to the metabolic
status and BMD in children with cancer.
PMID- 27489592
TI - Human Platelet Lysate as a Xeno Free Alternative of Fetal Bovine Serum for the In
Vitro Expansion of Human Mesenchymal Stromal Cells.
AB - BACKGROUND: Mesenchymal stromal cells (MSCs) are employed in various different
clinical settings in order to modulate immune response. Human autologous and
allogeneic supplements including platelet derivatives such as platelet lysate
(PL), platelet-released factors (PRF) and serum are assessed in clinical studies
to replace fetal bovine serum (FBS). The immunosuppressive activity and multi
potential characteristic of MSCs appear to be maintained when the cells are
expanded in platelet derivatives. MATERIALS AND METHODS: Platelet-rich plasma was
collected from umbrical cord blood (UCB). Platelet-derived growth factors
obtained by freeze and thaw methods. CD62P expression was determined by flow
cytometry. The concentration of PDGF-BB and PDGF-AB was detemined by ELISA. We
tested the ability of a different concentration of PL-supplemented medium to
support the ex vivo expansion of Wharton's jelly derived MSCs. We also
investigated the biological/functional properties of expanded MSCs in presence of
different concentration of PL. The conventional karyotyping was performed in
order to study the chromosomal stability. The gene expression of Collagen I and
II aggrecan and SOX-9 in the presence of different concentrations of PL was
evaluated by Real-time PCR. RESULTS: We observed 5% and 10% PL, causing greater
effects on proliferation of MSCs .These cells exhibited typical morphology,
immunophenotype and differentiation capacity. The genetic stability of these
derivative cells from Wharton's jelly was demonstrated by a normal karyotype.
Furthermore, the results of Real-time PCR analysis showed that the expression of
chondrocyte specific genes was higher in MSCs in the presence of 5% and 10% PL,
compared with FBS supplement. CONCLUSIONS: We demonstrated that PL could be used
as an alternative safe source of growth factors for expansion of MSCs and also
maintained similar growing potential and phenotype without any effect on
chromosomal stability.
PMID- 27489594
TI - Difficult Diagnosis of Colon Adenocarcinoma Metastasis to Retina: A Case Report
and Literature Review.
AB - Intraocular metastatic tumors have been increasingly reported in the recent past.
Unlike choroidal metastasis, metastasis to retina is very rare and so far has
been reported in very few case reports only. A 56 year-old male who presented
with a history of adenocarcinoma of the cecum and underwent lap colectomy for the
primary cecal tumor, received adjuvant chemotherapy for a year after surgery and
decided to stop. He was also diagnosed with metastasis to liver and lung at this
time. He presented with left eye pain, pressure and decreased vision suspicious
for retinal metastasis from cecal primary lesion, 2 years after initial
diagnosis. A mass of 5 x 10 mm was found on ophthalmoscopic examination and on
ultrasound of the eye, in spite of normal results of MRI of the orbit. Palliative
radiation therapy of the left eye resulted in decreased eye pressure and improved
vision. As retinal metastasis carries a poorer prognosis due to higher risk of
spread to central nervous system, the diagnosis of retinal metastasis in case of
gastrointestinal cancers patients who present with vision changes should be made
urgently. These patients should be thoroughly investigated with a synergistic
approach of opthalmoscopic examination, ultrasound of the eye along with other
imaging modalities like MRI of the orbit and just not MRI of orbit. Immediate
action in the form of surgical or radiation treatments of the metastatic tumors
of the eye should be instituted early on for a better prognosis.
PMID- 27489595
TI - Clavicular Chondrosarcoma: A Case Report and Brief Review of the Literature.
AB - Clavicular bone tumors occur in less than 0.5 percent of bone tumors. Primary
chondrosarcoma is very rare even among clavicle tumors. The main symptom is a
touchable mass in 69 % of patients. Dedicated centers using FNA and cytology can
reach a correct diagnosis in 94% of cases. Treatment planning is done using
simple X-ray, CT-scan, shoulder MRI, chest CT-scan and whole body technetium
scan. Treatment of choice for primary chondrosarcoma of clavicle is surgical
resection.
PMID- 27489593
TI - The Role of MicroRNAs in Myeloproliferative Neoplasia.
AB - MiRs are 17-25 nucleotide non-coding RNAs. These RNAs target approximately 80% of
protein coding mRNAs. MiRs control gene expression and altered expression of them
affects the development of cancer. MiRs can function as tumor suppressor via down
regulation of proto-oncogenes and may function as oncogenes by suppressing tumor
suppressors. Myeloproliferative neoplasias (formerly known as chronic
myeloproliferative disorders) form a class of hematologic malignancies
demonstrating the expansion of stem cells in one or more hematopoietic cell
lines. CML results from an acquired translocation known as BCR-ABL (Philadelphia
chromosome). JAK2V617F mutation is present in over 95% of PV, 55% of ET and 65%
of PMF cases. Aberrant expression of miR is associated with myeloproliferative
neoplasias, pathogenesis, disease progress and response to treatment. MiRs can
also be potential therapeutic targets. CML is mainly treated by tyrosine kinase
inhibitors such as Imatinib. In addition, altered function of miRs may be used as
a prognostic factor in treatment. Resistance to Imatinib is currently a major
clinical problem. The role of a number of miRs has been demonstrated in this
resistance. Changing expression pattern of miRs can be effective in response to
treatment and inhibition of drug resistance. In this paper, we set out to
evaluate the effect of miRs in pathogenesis and treatment of MPN.
PMID- 27489596
TI - Periprocedural considerations of transcatheter aortic valve implantation for
anesthesiologists.
AB - Transcatheter aortic valve replacement (TAVR) is rapidly gaining popularity as a
viable option in the management of patients with symptomatic aortic stenosis (AS)
and high risk for open surgical intervention. TAVR soon expanding its indications
from "high-risk" group of patients to those with "intermediate-risk". As an
anesthesiologist; understanding the procedure and the challenges inherent to it
is of utmost importance, in order to implement optimal care for this generally
frail population undergoing a rather novel procedure. Cardiac anesthesiologists
generally play a pivotal role in the perioperative care of the patients, and
therefore they should be fully familiar with the circumstances occurring
surrounding the procedure. Along with increasing experience and technical
developments for TAVR, the procedure time becomes shorter. Due to this
improvement in the procedure time, more and more anesthesiologists feel
comfortable in using monitored anesthesia care with moderate sedation for
patients undergoing TAVR. A number of complications could arise during the
procedure needing rapid diagnoses and occasionally conversion to general
anesthesia. This review focuses on the periprocedural anesthetic considerations
for TAVR.
PMID- 27489597
TI - Association of serum uric acid level with mortality and morbidity of patients
with acute ST-elevation myocardial infarction.
AB - INTRODUCTION: Investigating the clinical impact of serum uric acid (UA) and its
lowering agents on the complications and mortality of acute ST-elevation
myocardial infarction (STEMI) can open a new era in STEMI treatment. The aim of
this study was to evaluate the effect of on admission serum UA level on the
mortality and morbidity of patients admitted with STEMI. METHODS: A number of 608
patients with STEMI were enrolled in this study from December 21, 2012 until
February 19, 2014. Patients were followed for 20 months. Male to female ratio was
2.53, and the mean age of patients was 62.6+/-13.4. The relationship between the
level of UA and patients' mortality and morbidity, left ventricular ejection
fraction (LVEF), atrial and ventricular arrhythmia was analyzed. RESULTS:
Patients with high serum UA level had higher Killip class after STEMI (P=0.001).
Mean LVEF was measured to be 39.5+/-9.6 in normal UA group and 34.6+/-11.6 in
high UA group (P=0.001). In comparison with normal UA group, high UA group had
significantly higher cTnI (2.68+/-0.09 vs 4.09+/-0.42, respectively, P=0.001),
increased blood pressure (P=0.009), and higher atrial fibrillation (AF)
occurrence (P=0.03), but no association was seen between ventricular tachycardia
and serum UA level. Short term and midterm mortality were not different in two
groups (P=0.44 and 0.31, respectively). CONCLUSION: In the current study, high
serum UA level in patients with acute myocardial infarction (MI) was not
associated with higher in-hospital or midterm mortality, but it was associated
with lower LVEF, higher Killip class, elevated cTnI, creatinine, triglyceride,
and higher AF.
PMID- 27489598
TI - Serum cortisol level and adrenal reserve as a predictor of patients' outcome
after successful cardiopulmonary resuscitation.
AB - INTRODUCTION: It is thought that pituitary-adrenal axis has a fundamental role in
outcome of cardiopulmonary arrest (CPA). This study designed to evaluate the
correlation between adrenal reserve and post-resuscitation outcome. METHODS: In
this clinical trial study, 52 consecutive patients with CPA were enrolled in two
emergency departments (EDs) over a 3-month period. Plasma cortisol level was
measured at the beginning of CPR. Intravenous adrenocorticotropic hormone (ACTH)
stimulation test was carried out after successful CPR, and blood samples were
taken at 30 and 60 minutes, and 24 hours thereafter. Patients were divided into
two groups: in-hospital death or hospital discharge. RESULTS: In patients who
died, baseline and post-ACTH serum cortisol after 30 and 60 minutes and 24 hours
were higher than patients who discharged from the hospital, but it was not
statistically significant except to that of minute 60 (P=0.49). A model of
multivariate logistic regression analysis showed that age and need for
vasopressor infusion correlated with mortality. CONCLUSION: Current study could
not show the statistically significant difference in initial and post-ACTH serum
cortisol levels between survivor and non-survivor patients with cardiac arrest
who had initial successful CPR, except to that of minute 60.
PMID- 27489599
TI - Effect of ischemic postconditioning on myocardial protection in patients
undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass.
AB - INTRODUCTION: Reperfusion injury is a well-known phenomenon following restoration
of the coronary circulation after coronary artery bypass grafting (CABG) that
impairs myocardial function. In order to control the severity of this injury, we
aimed to investigate the effect of a new conditioning strategy namely ischemic
postconditioning (IPOC) along with controlled aortic root reperfusion (CARR) on
myocardial protection in CABG surgery with cardiopulmonary bypass. METHODS: In a
doubled blind clinical trial study, 51 patients undergoing first-time elective
CABG were randomly divided in three groups: CARR, IPOC, and combination of IPOC
and CARR. At the end of procedure and just before aortic cross-clamp removal,
reperfusion was started as following: In CARR-receiving groups, the reperfusion
was started with low perfusion pressures for 10 minutes, and in IPOC-receiving
groups, three cycles of 1 minute episodes of ischemia separated by 1 minute
episodes of reperfusion was applied as postconditioning protocol. Left
ventricular ejection fraction (EF) (by echocardiography), inotrope requirement
index, and myocardial arrhythmias were measured up to 72 hours after operation.
RESULTS: Echocardiography revealed that the recovery of EF after operation in
IPOC group was significantly higher than those of two other groups (P < 0.05).
Inotropic support requirement was significantly lower in IPOC groups. In
addition, the incidence of atrial and ventricular arrhythmias after opening of
aortic clamp and in intensive care unit (ICU) as well as recovery time of cardiac
rhythm upon reperfusion were lowered by administration of IPOC, as compared with
CARR group. CONCLUSION: The study suggests that IPOC may provide clinical
benefits against reperfusion injury in patients undergoing CABG surgery and
maintain the post ischemic left ventricular performance.
PMID- 27489600
TI - Comparison of current practices of cardiopulmonary perfusion technology in Iran
with American Society of Extracorporeal Technology's standards.
AB - INTRODUCTION: Standards have a significant role in showing the minimum level of
optimal optimum and the expected performance. Since the perfusion technology
staffs play an the leading role in providing the quality services to the patients
undergoing open heart surgery with cardiopulmonary bypass machine, this study
aimed to assess the standards on how Iranian perfusion technology staffs evaluate
and manage the patients during the cardiopulmonary bypass process and compare
their practice with the recommended standards by American Society of
Extracorporeal Technology. METHODS: In this descriptive study, data was collected
from 48 Iranian public hospitals and educational health centers through a
researcher-created questionnaire. The data collection questionnaire assessed the
standards which are recommended by American Society of Extracorporeal Technology.
RESULTS: Findings showed that appropriate measurements were carried out by the
perfusion technology staffs to prevent the hemodilution and avoid the blood
transfusion and unnecessary blood products, determine the initial dose of heparin
based on one of the proposed methods, monitor the anticoagulants based on ACT
measurement, and determine the additional doses of heparin during the
cardiopulmonary bypass based on ACT or protamine titration. It was done only in
4.2% of hospitals and health centers. CONCLUSION: Current practices of
cardiopulmonary perfusion technology in Iran are inappropriate based on the
standards of American Society of Cardiovascular Perfusion. This represents the
necessity of authorities' attention to the validation programs and development of
the caring standards on one hand and continuous assessment of using these
standards on the other hand.
PMID- 27489601
TI - Comparison of the patient radiation exposure during coronary angiography and
angioplasty procedures using trans-radial and trans-femoral access.
AB - INTRODUCTION: Cardiac catheterization procedure through the trans-radial access
(TRA) have shown many clinical advantages over the trans-femoral (TFA), but
despite its advantages, there are serious concerns regarding higher possible
radiation dose for the patients and operators in TRA. This study was planned to
compare the patients' radiation dose associated with TRA and TFA during coronary
angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA).
METHODS: Of 700 candidates for angiography, 326 patients were entered the study.
All the procedures were carried out by one interventional cardiologist employing
the same angiography unit in Aalinasab hospital and the patients' dose area
product (DAP), air kerma (AK), fluoroscopy time (FT) and cine film time (CFT)
were then determined in both access groups (TRA,TFA) in CA, PTCA and CA+PTCA
procedures. RESULTS: The mean FT, CFT and AK values in both TRA & TFA groups were
the same in all procedures (P>0.05). The mean DAP in CA+PTCA procedures was
6704.01+/-3243.23 uGym(2) in femoral access compare with 5647.46+/-2797.74
uGym(2) in radial access, which were significantly less than that in TFA with P=
0.02. CONCLUSION: On the basis of the results obtained in this study, no
differences were found in patients' radiation dose in both access groups,
therefore with regard to comparatively more clinical advantages associated with
the Trans-radial access technique it might be a good substitute for Trans-femoral
access.
PMID- 27489602
TI - Effect of Ventolin on QTc in children with respiratory distress.
AB - INTRODUCTION: beta2-agonists are first election drugs for the treatment of
respiratory disease that may alter cardiac autonomic modulation. The aim of this
study was to evaluate the effects of nebulized Ventolin on electrocardiogram,
particularly QTc interval to assess the potential arrhythmogenic risks. METHODS:
A total of 192 patients between 2 months and 15 years which received nebulized
Ventolin were enrolled in this study. Patients were divided into two groups.
Electrocardiograms of patients before and after nebulized Ventolin were taken.
Differences between two groups were assessed using a paired student's t test.
RESULTS: There was statistically significant differences in QTc before and after
Ventolin in each groups (P<0.005).Ventolin effect on QTc interval in both groups
did not differ. In first group, there was statistically significant differences
between heart rate before and after Ventolin taken (P=0.009) but in second group
there was not statistically significant differences between heart rate (P=0.345).
CONCLUSION: Although Ventolin can cause changes in QTc, Ventolin with 0.15
mg/kg/dose in comparison with 0.1 mg/kg/dose does not cause significant changes
in QTc.
PMID- 27489603
TI - Simultaneous thrombosis of multiple coronary arteries in a patient with
rheumatoid arthritis.
AB - We present a case of simultaneous coronary thrombosis of the left main, the left
anterior descending artery and the right coronary artery in a patient, recently
diagnosed with rheumatoid arthritis.
PMID- 27489604
TI - Multiple coronary thrombosis.
PMID- 27489605
TI - Prevention and Treatment of White Spot Lesions During and After Treatment with
Fixed Orthodontic Appliances: a Systematic Literature Review.
AB - OBJECTIVES: The aim of the systematic literature review is to update the evidence
for the prevention of white spot lesions, using materials containing fluoride
and/or casein phosphopeptide-amorphous calcium phosphate during and after
treatment with fixed orthodontic appliances. MATERIAL AND METHODS: Information
search for controlled studies on humans published between January 2008 and
February 2016 was performed in PubMed, ScienceDirect, Embase, The Cochrane
Library. Inclusion criteria were: the English language, study on humans, patients
undergoing orthodontic treatment with fixed appliances, randomized or quasi
randomized controlled clinical studies fluoride-containing product or casein
derivates used throughout the appliance therapy or straightaway after debonding.
RESULTS: 326 articles were reviewed (Embase 141, PubMed 129, ScienceDirect 41,
Cochrane 15). Twelve clinical studies fulfilled all inclusion criteria. Use of
fluoridated toothpaste had a remineralizing effect on white spot lesions (WSLs)
(P < 0.05); fluoride varnish and casein supplements were effective in prevention
and early treatment of WSLs (P < 0.05). CONCLUSIONS: Early detection of white
spot lesions during orthodontic treatment would allow implementing preventive
measures to control the demineralization process before lesions progress. The
systemic review has showed that the usage of fluoride and casein supplements in
ameliorating white spot lesions during and after fixed orthodontic treatment is
significantly effective. However the use of casein phosphopeptide-amorphous
calcium phosphate can be more beneficial than fluoride rinse in the reduction of
demineralization spots.
PMID- 27489606
TI - Inflammatory Cytokines Interleukin-1beta and Tumour Necrosis Factor-alpha - Novel
Biomarkers for the Detection of Periodontal Diseases: a Literature Review.
AB - OBJECTIVES: The article aims to discuss the IL-1beta and TNF-alpha potential use
as salivary biomarkers of periodontal diseases pathogenesis and progression.
MATERIAL AND METHODS: This literature review has been registered in PROSPERO
database with following number: CRD42016035729. Data investigation was performed
on PubMed database as the main source of studies. The following search terms were
used: "salivary biomarkers", "periodontal diseases", "TNF-alpha", "Interleukin-1
beta". Clinical trials and animal experimental models of periodontal disease were
included in the discussion. In regards to inclusive dates, published studies from
January 2006 to December 2015 were considered in this review along with the
mentioned inclusion criteria. RESULTS: IL-1beta and TNF-alpha salivary levels
increased in diseased groups, they were associated with onset and disease
severity, and their levels reduced in response to periodontal therapy. IL-1beta
and TNF-alpha could be promising biomarkers in the detection of periodontal
diseases. CONCLUSIONS: The use of a salivary cytokine-based diagnosis appears to
be a screening method capable of diagnosing periodontal diseases in an early
fashion, establishing an era of individualized clinical decisions.
PMID- 27489607
TI - Designing for Safety: Implications of a Fifteen Year Review of Swallowed and
Aspirated Dentures.
AB - OBJECTIVES: Dentures are worn by around 20% of the population, yet if they become
displaced they may enter the gastrointestinal or respiratory system, sometimes
with grave consequences. The aim of this study was to review recent published
literature in order to identify the epidemiology of patients and characteristics
of swallowed and aspirated dental prostheses, and propose strategies to minimise
these risks. MATERIAL AND METHODS: A fifteen year retrospective of published case
series and case reports was carried out. Photographs, radiographs and
descriptions of the dental prostheses were gathered, as well as the patient's
presenting complaint, the anatomical site where the denture was caught and the
procedure required to remove the denture. RESULTS: Ninety one separate events of
swallowed or aspirated dentures were identified from 83 case reports and series
from 28 countries. Average age was 55 years, and these were 74% male. Photographs
were retrieved for 49 of these dentures. Clasps were present in 25 of the
dentures. There was no significant difference between clasped and unclasped
dentures for perforation rates, need for open surgery and spontaneously passed
dentures. CONCLUSIONS: We discuss the implications of this study regarding
denture designs, specifically the importance of using a radiopaque acrylic, using
clasps when required even if there is a risk of aspiration, advising patients to
return if a denture is loose or damaged, and finally that all patients who wear a
denture are at risk of aspiration and swallowing events, and associated morbidity
and mortality.
PMID- 27489608
TI - Micro-CT Analysis of Bone Healing in Rabbit Calvarial Critical-Sized Defects with
Solid Bioactive Glass, Tricalcium Phosphate Granules or Autogenous Bone.
AB - OBJECTIVES: The purpose of the present study was to evaluate bone healing in
rabbit critical-sized calvarial defects using two different synthetic scaffold
materials, solid biodegradable bioactive glass and tricalcium phosphate granules
alongside solid and particulated autogenous bone grafts. MATERIAL AND METHODS:
Bilateral full thickness critical-sized calvarial defects were created in 15 New
Zealand white adult male rabbits. Ten defects were filled with solid scaffolds
made of bioactive glass or with porous tricalcium phosphate granules. The healing
of the biomaterial-filled defects was compared at the 6 week time point to the
healing of autologous bone grafted defects filled with a solid cranial bone block
in 5 defects and with particulated bone combined with fibrin glue in 10 defects.
In 5 animals one defect was left unfilled as a negative control. Micro-computed
tomography (micro-CT) was used to analyze healing of the defects. RESULTS: Micro
CT analysis revealed that defects filled with tricalcium phosphate granules
showed new bone formation in the order of 3.89 (SD 1.17)% whereas defects treated
with solid bioactive glass scaffolds showed 0.21 (SD 0.16)%, new bone formation.
In the empty negative control defects there was an average new bone formation of
21.8 (SD 23.7)%. CONCLUSIONS: According to findings in this study, tricalcium
phosphate granules have osteogenic potential superior to bioactive glass, though
both particulated bone with fibrin glue and solid bone block were superior defect
filling materials.
PMID- 27489609
TI - Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral
Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation.
AB - OBJECTIVES: The aim of the present study was to assess the skeletal stability
after large mandibular advancement (> 10 mm) with bilateral sagittal split
osteotomy and skeletal elastic intermaxillary fixation and to correlate the
skeletal stability with the vertical facial type. MATERIAL AND METHODS: A total
of 33 consecutive patients underwent bimaxillary surgery to correct skeletal
Class II malocclusion with a mandibular advancement (> 10 mm) measured at B-point
and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal
stability was evaluated using lateral cephalometric radiographs obtained
preoperative (T1), 8 weeks postoperatively (T2), and 18 month postoperatively
(T3). B-point and pogonion (Pog) was used to measure the skeletal relapse and the
mandibular plane angle (MP-angle) was used to determine the vertical facial type.
RESULTS: The mean advancement from T1 to T2 were 11.6 mm and 13.5 mm at B-point
and Pog, respectively. The mean skeletal relapse from T2 to T3 was -1.3 mm at B
point and -1.6 mm at Pog. The nineteen patients characterized as long facial
types, showed the highest amount of skeletal relapse (-1.5 mm at B-point and -1.9
mm at Pog). CONCLUSIONS: The present study showed a limited amount of skeletal
relapse in large mandibular advancement (> 10 mm) with bilateral sagittal split
osteotomy and skeletal elastic intermaxillary fixation. Bilateral sagittal split
osteotomy in combination with skeletal intermaxillary fixation can therefore be
an alternative to distraction osteogenesis in large mandibular advancements.
PMID- 27489610
TI - Vertical Craniofacial Morphology and its Relation to Temporomandibular Disorders.
AB - OBJECTIVES: This study investigated the association between craniofacial
morphology and temporomandibular disorders in adults. The influence of different
craniofacial morphologies on painful temporomandibular disorders was also
evaluated. MATERIAL AND METHODS: A total of 200 subjects were selected, including
100 with temporomandibular disorders (TMD) and 100 without TMD (control),
diagnosed by research diagnostic criteria for temporomandibular disorders. All
subjects were submitted to lateral cephalometric radiographs, and classified as
brachyfacial, mesofacial, or dolichofacial by Ricketts' analysis. Data were
analysed by Tukey-Kramer and Chi-square tests. RESULTS: No association between
craniofacial morphology and TMD was found (P = 0.6622). However, brachyfacial
morphology influences the presence of painful TMD (P = 0.0077). CONCLUSIONS:
Craniofacial morphology is not related to temporomandibular disorders in general.
PMID- 27489611
TI - The phenotypic plasticity of developmental modules.
AB - BACKGROUND: Organisms develop and evolve in a modular fashion, but how individual
modules interact with the environment remains poorly understood. Phenotypically
plastic traits are often under selection, and studies are needed to address how
traits respond to the environment in a modular fashion. In this study, tissue
specific plasticity of melanic spots was examined in the large milkweed bug,
Oncopeltus fasciatus. RESULTS: Although the size of the abdominal melanic bands
varied according to rearing temperatures, wing melanic bands were more robust. To
explore the regulation of abdominal pigmentation plasticity, candidate genes
involved in abdominal melanic spot patterning and biosynthesis of melanin were
analyzed. While the knockdown of dopa decarboxylase (Ddc) led to lighter
pigmentation in both the wings and the abdomen, the shape of the melanic elements
remained unaffected. Although the knockdown of Abdominal-B (Abd-B) partially
phenocopied the low-temperature phenotype, the abdominal bands were still
sensitive to temperature shifts. These observations suggest that regulators
downstream of Abd-B but upstream of DDC are responsible for the temperature
response of the abdomen. Ablation of wings led to the regeneration of a smaller
wing with reduced melanic bands that were shifted proximally. In addition, the
knockdown of the Wnt signaling nuclear effector genes, armadillo 1 and armadillo
2, altered both the melanic bands and the wing shape. Thus, the pleiotropic
effects of Wnt signaling may constrain the amount of plasticity in wing melanic
bands. CONCLUSIONS: We propose that when traits are regulated by distinct pre
patterning mechanisms, they can respond to the environment in a modular fashion,
whereas when the environment impacts developmental regulators that are shared
between different modules, phenotypic plasticity can manifest as a
developmentally integrated system.
PMID- 27489612
TI - The developmental and genetic bases of apetaly in Bocconia frutescens
(Chelidonieae: Papaveraceae).
AB - BACKGROUND: Bocconia and Macleaya are the only genera of the poppy family
(Papaveraceae) lacking petals; however, the developmental and genetic processes
underlying such evolutionary shift have not yet been studied. RESULTS: We studied
floral development in two species of petal-less poppies Bocconia frutescens and
Macleaya cordata as well as in the closely related petal-bearing Stylophorum
diphyllum. We generated a floral transcriptome of B. frutescens to identify MADS
box ABCE floral organ identity genes expressed during early floral development.
We performed phylogenetic analyses of these genes across Ranunculales as well as
RT-PCR and qRT-PCR to assess loci-specific expression patterns. We found that
petal-to-stamen homeosis in petal-less poppies occurs through distinct
developmental pathways. Transcriptomic analyses of B. frutescens floral buds
showed that homologs of all MADS-box genes are expressed except for the APETALA3
3 ortholog. Species-specific duplications of other ABCE genes in B. frutescens
have resulted in functional copies with expanded expression patterns than those
predicted by the model. CONCLUSIONS: Petal loss in B. frutescens is likely
associated with the lack of expression of AP3-3 and an expanded expression of
AGAMOUS. The genetic basis of petal identity is conserved in Ranunculaceae and
Papaveraceae although they have different number of AP3 paralogs and exhibit
dissimilar floral groundplans.
PMID- 27489614
TI - EphA5 and EphA6: regulation of neuronal and spine morphology.
AB - BACKGROUND: The Eph family of receptor tyrosine kinases plays important roles in
neural development. Previous studies have implicated Eph receptors and their
ligands, the ephrins, in neuronal migration, axon bundling and guidance to
specific targets, dendritic spine formation and neural plasticity. However,
specific contributions of EphA5 and EphA6 receptors to the regulation of neuronal
cell morphology have not been well studied. RESULTS: Here we show that deletion
of EphA5 and EphA6 results in abnormal Golgi staining patterns of cells in the
brain, and abnormal spine morphology. CONCLUSION: These observations suggest
novel functions of these Eph receptors in the regulation of neuronal and spine
structure in brain development and function.
PMID- 27489613
TI - Developmental expression of "germline"- and "sex determination"-related genes in
the ctenophore Mnemiopsis leidyi.
AB - BACKGROUND: An essential developmental pathway in sexually reproducing animals is
the specification of germ cells and the differentiation of mature gametes, sperm
and oocytes. The "germline" genes vasa, nanos and piwi are commonly identified in
primordial germ cells, suggesting a molecular signature for the germline
throughout animals. However, these genes are also expressed in a diverse set of
somatic stem cells throughout the animal kingdom leaving open significant
questions for whether they are required for germline specification. Similarly,
members of the Dmrt gene family are essential components regulating sex
determination and differentiation in bilaterian animals, but the functions of
these transcription factors, including potential roles in sex determination, in
early diverging animals remain unknown. The phylogenetic position of ctenophores
and the genome sequence of the lobate Mnemiopsis leidyi motivated us to determine
the compliment of these gene families in this species and determine expression
patterns during development. RESULTS: Our phylogenetic analyses of the vasa, piwi
and nanos gene families show that Mnemiopsis has multiple genes in each family
with multiple lineage-specific paralogs. Expression domains of Mnemiopsis nanos,
vasa and piwi, during embryogenesis from fertilization to the cydippid stage,
were diverse, with little overlapping expression and no or little expression in
what we think are the germ cells or gametogenic regions. piwi paralogs in
Mnemiopsis had distinct expression domains in the ectoderm during development. We
observed overlapping expression domains in the apical organ and tentacle
apparatus of the cydippid for a subset of "germline genes," which are areas of
high cell proliferation, suggesting that these genes are involved with "stem
cell" specification and maintenance. Similarly, the five Dmrt genes show diverse
non-overlapping expression domains, with no clear evidence for expression in
future gametogenic regions of the adult. We also report on splice variants for
two Mnemiopsis Dmrt genes that impact the presence and composition of the DM DNA
binding domain for these transcription factors. CONCLUSION: Our results are
consistent with a potential role for vasa, piwi and nanos genes in the
specification or maintenance of somatic stem cell populations during development
in Mnemiopsis. These results are similar to previous results in the tentaculate
ctenophore Pleurobrachia, with the exception that these genes were also expressed
in gonads and developing gametes of adult Pleurobrachia. These differences
suggest that the Mnemiopsis germline is either specified later in development
than hypothesized, the germline undergoes extensive migration, or the germline
does not express these classic molecular markers. Our results highlight the
utility of comparing expression of orthologous genes across multiple species. We
provide the first description of Dmrt expression in a ctenophore, which indicates
that Dmrt genes are expressed in distinct structures and regions during
development but not in future gametogenic regions, the only sex-specific
structure for this hermaphroditic species.
PMID- 27489615
TI - Exercise in space: the European Space Agency approach to in-flight exercise
countermeasures for long-duration missions on ISS.
AB - BACKGROUND: To counteract microgravity (uG)-induced adaptation, European Space
Agency (ESA) astronauts on long-duration missions (LDMs) to the International
Space Station (ISS) perform a daily physical exercise countermeasure program.
Since the first ESA crewmember completed an LDM in 2006, the ESA countermeasure
program has strived to provide efficient protection against decreases in body
mass, muscle strength, bone mass, and aerobic capacity within the operational
constraints of the ISS environment and the changing availability of on-board
exercise devices. The purpose of this paper is to provide a description of ESA's
individualised approach to in-flight exercise countermeasures and an up-to-date
picture of how exercise is used to counteract physiological changes resulting
from uG-induced adaptation. Changes in the absolute workload for resistive
exercise, treadmill running and cycle ergometry throughout ESA's eight LDMs are
also presented, and aspects of pre-flight physical preparation and post-flight
reconditioning outlined. RESULTS: With the introduction of the advanced resistive
exercise device (ARED) in 2009, the relative contribution of resistance exercise
to total in-flight exercise increased (33-46 %), whilst treadmill running (42-33
%) and cycle ergometry (26-20 %) decreased. All eight ESA crewmembers increased
their in-flight absolute workload during their LDMs for resistance exercise and
treadmill running (running speed and vertical loading through the harness), while
cycle ergometer workload was unchanged across missions. CONCLUSION: Increased or
unchanged absolute exercise workloads in-flight would appear contradictory to
typical post-flight reductions in muscle mass and strength, and cardiovascular
capacity following LDMs. However, increased absolute in-flight workloads are not
directly linked to changes in exercise capacity as they likely also reflect the
planned, conservative loading early in the mission to allow adaption to uG
exercise, including personal comfort issues with novel exercise hardware (e.g.
the treadmill harness). Inconsistency in hardware and individualised support
concepts across time limit the comparability of results from different
crewmembers, and questions regarding the difference between cycling and running
in uG versus identical exercise here on Earth, and other factors that might
influence in-flight exercise performance, still require further investigation.
PMID- 27489617
TI - 3D haptic modelling for preoperative planning of hepatic resection: A systematic
review.
AB - INTRODUCTION AND BACKGROUND: Three dimensional (3D) printing has gained
popularity in the medical field because of increased research in the field of
haptic 3D modeling. We review the role of 3D printing with specific reference to
liver directed applications. METHODS: A literature search was performed using the
scientific databases Medline and PubMed. We performed this in-line with the
PRISMA [20] statement. We only included articles in English, available in full
text, published about adults, about liver surgery and published between 2005 and
2015. The 3D model of a patient's liver venous vasculature and metastasis was
prepared from a CT scan using Osirix software (Pixmeo, Gineva, Switzerland) and
printed using our 3D printer (MakerBot Replicator Z18, US). To validate the
model, measurements from the inferior vena cava (IVC) were compared between the
CT scan and the 3D printed model. RESULTS: A total of six studies were retrieved
on 3D printing directly related to a liver application. While stereolithography
(STL) remains the gold standard in medical additive manufacturing, Fused Filament
Fabrication (FFF), is cheaper and may be more applicable. We found our liver 3D
model made by FFF had a 0.1 +/- 0.06 mm margin of error (mean +/- standard
deviation) compared with the CT scans. CONCLUSION: 3D printing in general surgery
is yet to be thoroughly exploited. The most relevant feature of interest with
regard to liver surgery is the ability to view the 3D dimensional relationship of
the various hepatic and portal veins with respect to tumor deposits when planning
hepatic resection. Systematic review registration number: researchregistry1348.
PMID- 27489618
TI - On the endoscopic methods used in pediatrics with questionable indications.
AB - *Partial isolation from international scientific community can result in
application of invasive methods without sufficient indications.*Performing
invasive procedures, the risk-to-benefit ratio should be kept as low as
possible.*Practical recommendations must be based on reliable and reproducible
research.
PMID- 27489619
TI - Surgical versus percutaneous techniques for peritoneal dialysis catheter
placement: A meta-analysis of the outcomes.
AB - BACKGROUND: Peritoneal dialysis (PD) is an effective method of renal replacement
therapy for end-stage renal disease patients. The PD catheter could be inserted
by surgical (open surgery/laparoscopic-assisted) or percutaneous techniques.
However, the efficacy of the techniques, including catheter survival and catheter
related complications, is still controversial. METHOD: The dataset was defined by
searching PubMed, EMBASE, Google Scholar and the Cochrane database that had been
published until July 2014. The meta-analysis was performed using Review Manager
Software version 5.2.6. RESULT: The final analysis was conducted on 10 studies (2
randomized controlled studies (RCTs) and 8 retrospective studies), including 1626
patients. The pooled data demonstrate no significant difference in 1-year
catheter survival (OR = 1.04, 95% CI = 0.52-2.10, P = 0.90) between surgical and
percutaneous groups. However, the sensitivity analysis of the RCTs demonstrated
that the incidence of overall infectious (OR = 0.26, 95% CI = 0.11-0.64, P =
0.003) and overall mechanical complications (OR = 0.32, 95% CI = 0.15-0.68, P =
0.003) were significantly lower in the percutaneous groups than the surgical
groups. Furthermore, the subgroup analyses revealed no significant difference in
the rates of peritonitis, tunnel and exit site infection, leakage, inflow-outflow
obstruction, bleeding and hernia by comparing the methods. CONCLUSION: The
results showed that the placement modality did not affect 1-year catheter
survival. Percutaneous catheter placement is as safe and effective as surgical
technique.
PMID- 27489620
TI - The art of self-knowledge and deduction in clinical practice.
AB - Clinical reasoning involves interviewing the patient, taking a history, and
carefully scrutinising objects in the environment, via a physical examination,
and the interpretation of medical results. Developments in medicine are trending
towards the routine use of sophisticated diagnostic tools. While important, these
trends may be leading clinicians to rely on expensive tests, while not using or
improving the art of clinical deduction. The ideal clinician knows themselves and
their environment, truly observes, imagines the possibilities, deduces from what
they observe, and continually learns. This allows the clinician to use all of
their senses, while not primarily relying on a diagnostic test.
PMID- 27489622
TI - Perioperative use of steroids in neonatal heart surgery: Evidence based practice
or tradition?
AB - A best evidence topic was written according to a structured protocol. The
question addressed was: Is the use of prophylactic, perioperative steroids
associated with better clinical outcomes following heart surgery in neonates?
Altogether, 194 papers were found using the reported search, of which 8
represented the best evidence to answer the clinical question. One study found
improved hospital survival in the group without steroids. Steroids increased
infection in one large retrospective study. Incidence of hyperglycaemia was
increased in the steroid group in 2 out of 5 studies. Use of steroids was
associated with a shorter duration of ventilation and better oxygenation in one
study. Postoperative steroid infusion was associated with reduced low cardiac
output syndrome, inotrope requirement and less fluid retention in two controlled
trials in which all patients received preoperative steroid. High dose steroid was
associated with renal dysfunction in one study, comparing single versus double
dose steroid prophylaxis. Steroid non-recipients had a shorter intensive care
length of stay in 2 out of 7 studies. We conclude that use of steroids
perioperatively does not unequivocally improve clinical outcome in neonatal heart
surgery. A large, multicentre prospective randomized controlled trial is needed
to clarify the role of steroids in paediatric heart surgery.
PMID- 27489621
TI - High-performance detection and early prediction of septic shock for alcohol-use
disorder patients.
AB - BACKGROUND: The presence of Alcohol Use Disorder (AUD) complicates the medical
conditions of patients and increases the difficulty of detecting and predicting
the onset of septic shock for patients in the ICU. METHODS: We have developed a
high-performance sepsis prediction algorithm, InSight, which outperforms existing
methods for AUD patient populations. InSight analyses a combination of singlets,
doublets, and triplets of clinical measurements over time to generate a septic
shock risk score. AUD patients obtained from the MIMIC III database were used in
this retrospective study to train InSight and compare performance with the
Modified Early Warning Score (MEWS), the Simplified Acute Physiology Score (SAPS
II), and the Systemic Inflammatory Response Syndrome (SIRS) for septic shock
prediction and detection. RESULTS: From 4-fold cross validation, InSight performs
particularly well on diagnostic odds ratio and demonstrates a relatively high
Area Under the Receiver Operating Characteristic (AUROC) metric. Four hours prior
to onset, InSight had an average AUROC of 0.815, and at the time of onset,
InSight had an average AUROC value of 0.965. When applied to patient populations
where AUD may complicate prediction methods of sepsis, InSight outperforms
existing diagnostic tools. CONCLUSIONS: Analysis of the higher order correlations
and trends between relevant clinical measurements using the InSight algorithm
leads to more accurate detection and prediction of septic shock, even in cases
where diagnosis may be confounded by AUD.
PMID- 27489623
TI - Laparoscopic colorectal resections with and without routine mechanical bowel
preparation: A comparative study.
AB - BACKGROUND: The benefit of mechanical bowel preparation (MBP) in patients
undergoing laparoscopic colorectal resections remains a question. This study
aimed to evaluate the effect of omitting MBP on patients undergoing laparoscopic
bowel resections. METHODS: The outcomes of patients who underwent elective
colorectal resections for cancer of colon and upper rectum without MBP were
compared to a retrospective cohort who had MBP. RESULTS: There were 97 patients
in the No-MBP group and 159 patients in the MBP group. Their mean age, operative
risk, tumor size and stage of disease were similar. There were no significant
differences in operative time and estimated blood loss. The anastomotic leakage
rate was 1.0% in the No-MBP group and 0.6% in the MBP group, (p = 1.00). Wound
infection rate were 4.1% and 3.8% in the No-MBP group and the MBP group
respectively (p = 1.00). Overall surgical morbidity rate was 11.3% in the No-MBP
group and 8.2% in the MBP group (p = 0.40). Conversion rates were 5.2% in the No
MBP group and 6.9% in the MBP group, (p = 0.57). CONCLUSION: The omission of
mechanical bowel preparation does not increase surgical morbidities in patients
undergoing laparoscopic bowel resections. It also has no effect on operating time
and conversion rate.
PMID- 27489624
TI - Digital rectal examination for initial assessment of the multi-injured patient:
Can we depend on it?
AB - BACKGROUND: Digital rectal examination (DRE) is part of the assessment of trauma
patients as recommended by ATLS((r)). The theory behind is to aid early diagnosis
of potential lower intestinal, urethral and spinal cord injuries. Previous
studies suggest that test characteristics of DRE are far from reliable. This
study examines the correlation between DRE findings and diagnosis and whether DRE
findings affect subsequent management. MATERIALS AND METHODS: Patients with ICD
10 codes for spinal cord, urethral and lower intestinal injuries were identified
from the trauma registry at an urban university hospital between 2007 and 2011. A
retrospective review of electronic medical records was carried out to analyse DRE
findings and subsequent management. RESULTS: 253 patients met the inclusion
criteria with a mean age of 44 +/- 20 years and mean ISS of 26 +/- 16. 160
patients had detailed DRE documentation with abnormal findings in 48%.
Sensitivity rate was 0.47. Correlational analysis between examination findings
and diagnosis gave a kappa of 0.12. Subsequent management was not altered in any
case due to DRE findings. CONCLUSION: DRE in trauma settings has low sensitivity
and does not change subsequent management. Excluding or postponing this
examination should therefore be considered.
PMID- 27489625
TI - Increased serum IgG4 levels and intimal IgG4-positive cell infiltration in
rapidly growing aortic aneurysm.
AB - A 67-year-old Japanese man had been complaining of discomfort in the chest and
back and feeling febrile for 2 weeks. Chest computed tomography indicated a
thoracic aortic aneurysm. He occasionally showed a high fever (up to 38.0 degrees
C), even after hospital admission, irrespective of antibiotic therapy. The
patient was found to have elevated serum IgG4 levels (366 mg/dL). The aneurysm
demonstrated rapid growth; therefore, rifampicin-soaked woven Dacron synthetic
graft replacement was performed 22 days after admission. Immunohistostatining of
the resected aorta segment showed an IgG4-positive plasma cell infiltrate within
the intimal layer neighboring the cholesterol-rich atheromatous plaque. After
surgery, the patient's serum IgG4 level dropped acutely; however, it did not
reach the normal range. The possible role of IgG4 in the development or
suppression of aortic remodeling, as well as in atherogenesis, among patients
with rapidly growing aortic aneurysm requires further investigation.
PMID- 27489626
TI - Presumed hydrochlorothiazide-associated immunologic-hypersensitivity-induced
pericardial effusion.
AB - A 50-year-old Caucasian female presented for a second opinion regarding a newly
diagnosed pericardial effusion. Seven months previously, hydrochlorothiazide was
introduced into her pharmacologic regimen to aid in the management of her
hypertension. A routine echocardiogram indicated a large pericardial effusion
with signs of early cardiac tamponade. The patient subsequently underwent
successful pericardiocentesis with complete drainage of the pericardial effusion.
The effusion was empirically attributed to a viral etiology. Repeat
echocardiograms showed recurrence of the pericardial effusion. Prior to
undergoing a second pericardiocentesis with pericardial biopsy, as her physicians
recommended, the patient sought a second opinion. While obtaining the patient's
history, an allergy to sulfa was elicited. The possibility that the pericardial
effusion may be secondary to an immunologic-hypersensitivity reaction was
considered. It was recommended the patient discontinue the use of
hydrochlorothiazide. Nine days following discontinuation of hydrochlorothiazide
and without any other intervention, an echocardiogram was reported to show the
size of the pericardial effusion had subsided substantially. Nine weeks following
discontinuation, almost complete resolution of the pericardial effusion was
reported. It is hypothesized that when treated with hydrochlorothiazide, the
patient had an immune response leading to the pericardial effusion.
PMID- 27489627
TI - Squamous cell carcinoma arising from congenital lymphedema.
AB - Congenital lymphedema is a rare type of primary lymphedema occurring at birth or
developing shortly later. Primary lymphedema can be classified according to
whether it is familial or sporadic. The primary congenital familial lymphedema is
also known as Milroy's disease. Majority of primary cases are sporadic type.
Chronic lymphedema can be secondary to infections, surgery with lymph node
excision, trauma, lymphadenectomy, radiotherapy, filarial infection, and so on.
It is recognized that a variety of malignant tumors can arise in chronic
congenital or acquired lymphedema; the most documented associations are
lymphangiosarcoma, basal cell carcinoma, lymphoma, malignant melanoma, and
Kaposi's sarcoma. A total of 13 cases of squamous cell carcinoma arising from
chronic (primary or acquired) lymphedema have been reported, and only 3 cases of
congenital lymphedema presented with squamous cell carcinoma as reported. A 32
year-old young male presented with chronic unilateral left lower limb lymphedema
of 28 years duration. In addition, he had a 3-month history of a fungating
cutaneous lesion on the lateral side measuring 2 cm * 1 cm in size. Fine-needle
aspiration cytology was performed on the later mass, and a diagnosis of
angiosarcoma was made. At histopathology, the appearances did not confirm
angiosarcoma. However, an impression of carcinoma was made as squamous cells were
observed in sheets. Immunohistochemistry was performed using markers for CD31,
factor VIII (FVIII), and MiB. The epithelial marker cytokeratin was positive for
squamoid cells and MiB index of 75%. The vascular markers FVIII and CD31 were
negative, thus ruling out angiosarcoma. The final diagnosis was given as
infiltrating squamous cell carcinoma in chronic lymphedema.
PMID- 27489628
TI - A patient with profound weight loss after gastric bypass surgery: A case report.
AB - INTRODUCTION: A case of profound weight loss after gastric bypass surgery with
multiple negative evaluations. CASE PRESENTATION: A 41-year-old African-American
female presented with greater-than-expected weight loss after gastric bypass and
increasing abdominal pain over a 2-year period. An extensive workup was pursued
for the patient with blood analysis, tumor markers, imaging studies both computed
tomography and magnetic resonance imaging, arterial studies, and endoscopy from
above and below, all of which demonstrated normal results. The patient was
followed up without improvement, and repeated studies were also normal. The
patient was labeled with a nonorganic etiology for her symptoms, which led to a
psychiatry referral which was refused. CONCLUSION: The patient's surgeon, who
already had removed a normal appendix and gallbladder, repeated a laparoscopic
exam. The exam was normal except for a small focus of pancreatic cancer in the
celiac plexus. The patient died from perioperative sepsis from peritonitis 2 days
after surgery. The case is discussed and findings reviewed.
PMID- 27489629
TI - A case of mistaken identity: When lupus masquerades as primary myelofibrosis.
AB - INTRODUCTION: Autoimmune myelofibrosis is an uncommon hematologic disease
characterized by anemia, bone marrow myelofibrosis, and an autoimmune feature.
Myelofibrosis is often associated with other conditions, including infections,
nutritional/endocrine dysfunction, toxin/drug exposure, and connective tissue
diseases, including scleroderma and systemic lupus erythematosus. Absence of
clonal markers (JAK2) and heterogeneity of the symptoms often complicate the
diagnosis. CASE PRESENTATION: Here, we present two cases of systemic lupus
erythematosus-induced autoimmune myelofibrosis. The first case is of a 36-year
old African American female with diagnosis of systemic lupus erythematosus at the
age of 12 years. The second patient is a 44-year-old African American male with
family history of systemic lupus erythematosus who developed anemia and
constitutional symptoms later on. Both patients showed hypercellularity and
fibrotic changes of the bone marrow. Moreover, mutational analysis showed that
both patients were wild type for JAK2 (V617F and exon 12) and MPL (exon 10).
CONCLUSIONS: These two cases illustrate that anemic patients with fibrotic
changes in the bone marrow without other clinicopathologic features associated
with primary myelofibrosis in the presence of clinical manifestations and history
of an autoimmune disease should suggest an autoimmune myelofibrosis. These cases
demonstrate that a good clinical history combined with molecular technologies and
pathomorphologic criteria are helpful in distinguishing between primary
myelofibrosis and a nonclonal myelofibrosis from an associated condition.
PMID- 27489630
TI - Palliative care consults in oncology: what are we waiting for? A case report.
AB - Palliative care focuses on symptom management and decreased suffering in all
aspects of health. Although it has been shown that palliative care improves
emotional and clinical outcomes for patients and families, it remains an
underutilized specialty particularly in the field of oncology. Involving cancer
patients in palliative care can sometimes be confused with the idea of giving up,
or losing hope. This is especially true when patients are young. The following
case report provides an example of a patient who may have benefited from
palliative specialists' involvement early in his disease, potentially sparing him
and his family prolonged, physical, and emotional suffering.
PMID- 27489631
TI - Isolated infrarenal abdominal aorta aneurysm in a 42-year-old patient with
Marfan's syndrome: Case report.
AB - Marfan's syndrome is an autosomal dominant disorder of connective tissue
characterized by a large number of possible mutations and by heterogeneity of
clinical presentation primarily in skeletal, ocular and cardiovascular organ
systems. Cardiovascular complications of the disease are responsible for high
mortality. The case of a 42-year-old patient with a progressive advanced
abdominal aorta dilatation visualized on computed tomography images is presented.
Pathogenesis, diagnosis and management of patients with Marfan's syndrome are
also discussed.
PMID- 27489632
TI - Elevated liver enzymes associated with dronedarone for atrial fibrillation.
AB - A 51-year-old male with documented atrial fibrillation who was taking dronedarone
400 mg twice daily for approximately 3 months returned to the cardiologist for an
ablation procedure. Baseline liver enzymes were within normal range prior to
starting the medication and increased after the 3 months of therapy. Aspartate
aminotransferase increased from 31 IU/L to 98 IU/L, and alanine aminotransferase
increased from 21 IU/L to 101 IU/L. Two and a half months after discontinuation
of the medication, liver enzymes normalized (aspartate aminotransferase: 30 IU/L
and alanine aminotransferase: 25 IU/L). The Food and Drug Administration has now
alerted health-care professionals of the potential for liver injury based upon
post-marketing surveillance. The chronological course of elevated liver enzymes
noted in our patient is suggestive of a dronedarone-induced problem. Clinicians
should have a heightened awareness of the potential for liver enzyme elevation
and injury with dronedarone and should monitor enzymes periodically, especially
within the first 6 months of use.
PMID- 27489633
TI - Hand replantation: A rare case report.
AB - We report a case of a hand replantation. A 43-year-old male presented with an
amputated right hand. After clinical and radiological examination of the
amputated hand and the forearm stump, the patient was consented for hand
replantation procedure. Both bones of the forearm were fixed using K-wires.
Careful dissection, trimming and repair of the tendons, vessels (two arteries and
one vein) and nerves was achieved. The patient tolerated the procedure well and 2
months later showed a progressive improvement in motor and sensory functions. We
suggest that a single-vein repair is sufficient for a successful hand
replantation.
PMID- 27489634
TI - Elevated international normalized ratio with the consumption of grapefruit and
use of warfarin.
AB - A 65-year-old male with documented atrial flutter who was taking warfarin
chronically returned to the anticoagulation clinic for follow-up, after having
been on 10 mg daily for approximately 2 weeks. He had a previous sub-therapeutic
international normalized ratio of 1.7 on a dose of 65 mg/week. The international
normalized ratio at this visit was now 4.77 via venipuncture, after just an 8%
increase in weekly dosing. He self-reported adherence to the new warfarin dosing
but had begun eating grapefruit since last visit. The patient had no active
bleeding and was told to decrease his dose to 8 mg daily. He also stopped eating
the grapefruit. One week later, he returned to the clinic and the international
normalized ratio was 2.1. He is currently back on warfarin 65 mg/week, and his
international normalized ratio has been within therapeutic range for the past 4
months. Clinicians should have a heightened awareness of the potential for
elevated international normalized ratio when grapefruit juice is consumed in a
patient who is taking warfarin.
PMID- 27489635
TI - Repetitive complications after prosthetic graft for inflammatory aortic aneurysm.
AB - The presence of retroperitoneal fibrosis after an aortic graft replacement is a
marker of poor prognosis following aortic graft replacement. Herein we report the
case of a 39-year-old man with retroperitoneal fibrosis that had been causing
ureteral obstruction. The man had undergone repeated aortic graft replacement due
to bacteremia and aortic graft-small intestinal fistula that occurred 4 years
after initial aortic grafting for an inflammatory aortic aneurysm. The patient
was discharged after 4 weeks of intravenous antibiotic therapy following the
latest aortic graft replacement.
PMID- 27489636
TI - Tocilizumab improved clinical symptoms of a patient with systemic tophaceous gout
who had symmetric polyarthritis and fever: An alternative treatment by blockade
of interleukin-6 signaling.
AB - Chronic tophaceous gout is the end stage of gout. We employed a blockade of
interleukin-6 signaling therapy by tocilizumab instead of anakinra, an
interleukin-1 receptor antagonist, for a 61-year-old Japanese woman diagnosed
with tophaceous gout. Laboratory data showed that serum interleukin-6
concentration was elevated. Serum interleukin-1beta concentration was under the
detectable level, although serum uric acid was elevated due to renal dysfunction.
The secretion patterns of interleukin-1beta, tumor-necrosis factor-alpha,
interleukin-6, and interleukin-8 from peripheral mononuclear cells isolated from
the patient exhibited no remarkable differences compared with those of healthy
volunteers. After treatment with the interleukin-6 receptor antagonist
tocilizumab, serum interleukin-6 concentration decreased followed by improved
clinical symptoms, such as reduced size of the subcutaneous nodules, no fever,
and no acute gouty attacks during the treatment. Our case suggests that
tocilizumab markedly improves clinical and laboratory manifestations in
tophaceous gout with arthritis and fever as well as interleukin-1 blockade
therapy.
PMID- 27489637
TI - A case report of anxiety disorder preceding frontotemporal dementia with
asymmetric right temporal lobe atrophy.
AB - Behavioral variant frontotemporal dementia presents with progressive loss of
social skills and cognition and is usually associated with asymmetric frontal or
temporal lobe involvement. This article reports about a patient with a long
history of anxiety disorder who later proceeded to develop behavioral variant
frontotemporal dementia. Further discussion about selective specific network
vulnerability and a possible link between these two conditions is provided.
PMID- 27489638
TI - A noninvasive biomechanical treatment as an additional tool in the rehabilitation
of an acute anterior cruciate ligament tear: A case report.
AB - OBJECTIVES: Conservative treatments for anterior cruciate ligament (ACL) tears
may have just as good an outcome as invasive treatments. These include muscle
strengthening and neuromuscular proprioceptive exercises to improve joint
stability and restore motion to the knee. The Purpose of the current work
presents was to examine the feasibility of a novel non-invasive biomechanical
treatment to improve the rehabilitation process following an ACL tear. This is a
single case report that presents the effect of this therapy in a patient with a
complete ACL rupture who chose not to undergo reconstructive surgery. METHODS: A
29-year old female athlete with an acute indirect injury to the knee who chose
not to undergo surgery was monitored. Two days after injury the patient began
AposTherapy. A unique biomechanical device was specially calibrated to the
patient's feet. The therapy program was initiated, which included carrying out
her daily routine while wearing the device. The subject underwent a gait analysis
at baseline and follow-up gait analyses at weeks 1, 2, 4, 8, 12 and 26. RESULTS:
A severe abnormal gait was seen immediately after injury, including a substantial
decrease in gait velocity, step length and single limb support. In addition, limb
symmetry was substantially compromised following the injury. After 4 weeks of
treatment, patient had returned to normal gait values and limbs asymmetry reached
the normal range. CONCLUSIONS: The results of this case report suggest that this
conservative biomechanical therapy may have helped this patient in her
rehabilitation process. Further research is needed in order to determine the
effect of this therapy for patients post ACL injuries.
PMID- 27489639
TI - Clinical impact of laboratory error on therapeutic drug monitoring of once-daily
tobramycin in cystic fibrosis: Case series.
AB - Once-daily dosing intravenous tobramycin is commonly used to treat cystic
fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic
drug monitoring data to individualize the dose among patients who have been
treated with tobramycin previously. This case series involves three patients with
cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once
daily dosing that produced therapeutic drug levels during a previous hospital
admission, raising questions about the validity of these levels. Investigation
into several potential sources of error led to the discovery of an analyzer error
in the laboratory. Once the laboratory's tobramycin analyzer was recalibrated,
the reported levels were comparable to historical levels. This case series
emphasizes the clinical importance of critically analyzing reported levels, and
specifically, the importance of utilizing past therapeutic drug monitoring data,
if available, for all patients treated with intravenous tobramycin. If a patient
was therapeutic on a similar dose of tobramycin during a previous admission, a
dose adjustment may not be necessary, and clinicians should consider repeating
levels while pursuing alternative explanations for the discrepant serum levels.
PMID- 27489640
TI - Left-sided thoracoscopy in the prone position for surgery of distal esophageal
benign pathologies.
AB - Exposure of the distal esophagus can be achieved by a wide variety of surgical
approaches. The standard procedure is mostly by laparoscopy. In cases where
laparoscopy is relatively contraindicated, thoracoscopy is preferred. In this
case, exposure of the distal esophagus from the aorta, heart and lung is
technically challenging using thoracoscopy in the right lateral decubitus
position. Surgery in the prone position for esophageal cancer has been
successfully described in previous literature. We present our experience with
left-sided thoracoscopy in the prone position in three patients with benign
distal esophageal pathologies. This approach provided a much better exposure of
the distal esophagus and enabled a successful surgery to be done in all patients
with less manipulation of the lung.
PMID- 27489641
TI - A six-time Ultraman winner and a normal heart: A case report.
AB - Number of subjects currently participating in high-endurance aerobic exercise
training regimens and competitions has substantially increased in recent years.
While there is no doubt that regular exercise practice is fundamental for the
maintenance of a good health, there have been reports of cardiac structural
changes of subjects exposed to strenuous endurance physical exercise. This
article reports a case of a 47-year-old male very successful sportsman-including
being a six-time Ultraman winner-who has accumulated more than 50,000 h of
training and competition in his 35-year career, averaging 25-30 h/week. Despite
this huge amount of aerobic exercise, about 25 times larger than typically
recommended dose for health purposes (i.e. 75 min of vigorous exercise per week),
no major abnormalities were detected in electrocardiograms (rest and maximal
exercise), transthoracic echocardiogram, and magnetic resonance imaging. In fact,
after this complete evaluation, his heart was found to be quite normal.
PMID- 27489642
TI - Improved myocardial perfusion after transmyocardial laser revascularization in a
patient with microvascular coronary artery disease.
AB - We report the case of a 59-year-old woman who presented with symptoms of angina
that was refractory to medical management. Although her cardiac catheterization
revealed microvascular coronary artery disease, her symptoms were refractory to
optimal medical management that included ranolazine. After undergoing
transmyocardial revascularization, her myocardial ischemia completely resolved
and her symptoms dramatically improved. This case suggests that combination of
ranolazine and transmyocardial revascularization can be applied to patients with
microvascular coronary artery disease.
PMID- 27489643
TI - Rheumatic heart disease in Tennessee: An overlooked diagnosis.
AB - Rheumatic heart disease, already a major burden in low- and middle-income
countries, is becoming an emerging problem in high-income countries. Although
acute rheumatic fever and rheumatic heart disease have almost been eradicated in
areas with established economies, the emergence of this problem may be
attributable to the migration from low-income to high-income settings. Between
2010 and 2012, we diagnosed a cluster of rheumatic heart disease cases in
children from the Middle Tennessee area. The goal of this report is to increase
awareness among clinicians as the incidence and prevalence of acute rheumatic
fever remain relatively significant in large US metropolitan areas. Although
acute rheumatic fever is seasonal, a high suspicion index may lead to the early
diagnosis and prevention of its cardiac complications. Furthermore, screening
procedures may be recommended for populations at risk for rheumatic heart disease
in endemic areas, and active surveillance with echocardiography-based screening
might become very important.
PMID- 27489644
TI - Cerebral contrast retention after difficult cardiac catheterization: Case report.
AB - BACKGROUND: We report a diagnostic dilemma in a rare case of cerebral contrast
retention after difficult cardiac catheterization in an elderly patient loaded
with prasugrel. SUMMARY: Our case report describes a 77-year-old female with
history of hypertension, diabetes, and dyslipidemia who presented to emergency
department complaining of chest pain. Patient was found to have an inferior wall
ST elevation myocardial infarction. The patient was loaded with aspirin and
prasugrel and taken for emergent cardiac catheterization. Cardiac catheterization
revealed two-vessel coronary artery disease with unsuccessful attempt of
percutaneous intervention. Immediately after procedure, patient developed an
episode of seizure. Emergent computed tomography scan of the brain revealed
hyperdensity in the right frontoparietal region consistent with intracerebral
bleed. Repeat computed tomography (24 h later) revealed substantial interval
improvement of hyperdensity. Follow-up magnetic resonance imaging of the head was
normal. Given the lack of magnetic resonance imaging changes, the rate of
resolution on computed tomography without expected subacute changes, and the lack
of neurologic findings, the initial hyperdensity seen on computed tomography of
the brain was believed to be secondary to contrast leakage during cardiac
catheterization as opposed to intracranial hemorrhage.
PMID- 27489645
TI - Swelling of bilateral parotid glands: An unusual symptom of multisystem
Langerhans cell histiocytosis.
AB - OBJECTIVE: Langerhans cell histiocytosis is an unusual disorder of unknown
etiology with heterogeneous clinical behaviors and variable outcomes. It can
involve one or more organs or systems, but to our best knowledge, parotid glands
involvement in Langerhans cell histiocytosis is extremely rare in English
literature. METHOD: We report a 13-month-old girl who presented with bilateral
parotid swelling as presenting symptom. She was misdiagnosed for 4 months, but
final diagnosis was multisystem Langerhans cell histiocytosis. RESULT: After
being treated for 18 months, the patient acquired complete remission and attained
similar growth status to other healthy children. CONCLUSION: Langerhans cell
histiocytosis may involve any organ; in patients with parotid enlargement,
Langerhans cell histiocytosis should be kept in mind in the differential
diagnoses. We emphasize the importance of biopsy for histologic evaluation as
soon as possible and even repeatedly if initial results are negative for
Langerhans cell histiocytosis.
PMID- 27489646
TI - Fatal case of cephalexin-induced toxic epidermal necrolysis.
AB - PURPOSE: To describe a case of toxic epidermal necrolysis likely caused by
cephalexin with a review of the literature. CASE: An 80-year-old male with a
known allergy to cephalosporins, residing at a long-term acute care hospital,
received cephalexin for a urinary tract infection. And 1 day after starting
therapy, the patient developed an extensive erythematous rash accompanied by skin
sloughing; 4 days after receiving cephalexin, the patient was directly admitted
to the burn intensive care unit and was diagnosed with toxic epidermal necrolysis
involving 56% of the total body surface area. Progressive deterioration to
multisystem organ failure ensued, and the patient died 5 days following his
admission to the burn intensive care unit. At the time of death, ulcerations were
noted over approximately 80% of his body. SUMMARY: The temporal association of
the patient's ingestion of cephalexin for a urinary tract infection to his onset
of toxic epidermal necrolysis suggests that this 80-year-old man developed toxic
epidermal necrolysis following the administration of cephalexin for a urinary
tract infection.
PMID- 27489647
TI - Heparin-induced thrombocytopenia among patients of a comprehensive cancer center.
AB - Most clinical studies of heparin-induced thrombocytopenia have not included
cancer patients who have high risk of thromboembolism, frequent exposure to
heparin, and many potential causes of thrombocytopenia other than heparin-induced
thrombocytopenia. To estimate the incidence and prevalence of heparin-induced
thrombocytopenia in cancer patients, we identified cases based on diagnostic
codes, anti-heparin antibody testing, and clinical characteristics (4T score) at
a comprehensive cancer center between 1 October 2008 and 31 December 2011. We
estimated that the prevalence of heparin-induced thrombocytopenia to be 0.02%
among all cancer patients and 0.24% among cancer patients exposed to heparin. The
annual incidence of heparin-induced thrombocytopenia was 0.57 cases per 1000
cancer patients exposed to heparin. Of the 40 cancer patients with the
International Classification of Diseases (Ninth Revision; ICD-9) code for heparin
induced thrombocytopenia, positive anti-heparin antibody, and 4T score >=4, 5
(12.5%) died of related thromboembolic or hemorrhagic complications. In a
multivariate logistic regression model, male gender was a significant (p = 0.035)
factor, and non-hematological malignancy was a significant (p = 0.017) factor
associated with anti-heparin antibody positivity. Future studies may further
examine the risk factors associated with heparin-induced thrombocytopenia in
larger cohorts.
PMID- 27489648
TI - Groin pain after metal-on-metal hip resurfacing prosthesis.
AB - Total hip replacement continues to be a widely successful operation, but
persistent groin pain following a metal-on-metal hip resurfacing remains a
problem for some patients. The concern regarding the safety and efficacy of metal
on-metal total hip replacements has been rising. We present the case of a 47-year
old man with groin pain after metal-on-metal hip resurfacing. We observed high
metal ion levels detected in blood analytical studies and a pseudotumor in
magnetic resonance imaging. Our patient was treated with a revision surgery. The
progressive elevation of blood and urine metal levels in the presence of
periarticular cysts and/or groin pain is a complication of metal-on-metal hip
arthroplasty and needs revision surgery.
PMID- 27489649
TI - Late-onset ornithine transcarbamylase deficiency: An under recognized cause of
metabolic encephalopathy.
AB - INTRODUCTION: Ornithine transcarbamylase deficiency is the most common inherited
disorder of the urea cycle, has a variable phenotype, and is caused by mutations
in the OTC gene. We report three cases of ornithine transcarbamylase deficiency
to illustrate the late-onset presentation of this disorder and provide strategies
for diagnosis and treatment. The patients were maternal first cousins, presenting
with hyperammonemia and obtundation. Urea cycle disorder was not initially
suspected in the first patient, delaying diagnosis. RESULTS: Sequencing of the
OTC gene showed a novel missense mutation, c.563G > C (p.G188A). Numerous family
members were found to carry this mutation, which shows a trend toward later
onset. Each urea cycle disorder has its own unique pattern of biochemical
abnormalities, which differ from non-metabolic causes of critical illness.
CONCLUSION: Regardless of age, clinical suspicion of a urea cycle disorder is
important in encephalopathic patients to ensure quick diagnosis and definitive
treatment of the underlying inborn error of metabolism.
PMID- 27489650
TI - Leukocytoclastic vasculitis in an adolescent with ulcerative colitis: Report of a
case and review of the literature.
AB - An adolescent female with long-standing, difficult-to-control ulcerative colitis
developed leukocytoclastic vasculitis, a rare cutaneous extra-intestinal
manifestation of the inflammatory bowel disease. The authors provide a literature
review on leukocytoclastic vasculitis complicating ulcerative colitis.
Furthermore, the clinical features of leukocytoclastic vasculitis are compared
and contrasted with the more common cutaneous extra-intestinal manifestations of
inflammatory bowel disease, erythema nodosum, and pyoderma gangrenosum.
PMID- 27489651
TI - Successful cases of difficult inferior vena cava filter retrieval with the use of
biopsy forceps: Biopsy forceps technique.
AB - OBJECTIVES: For treatment and prevention of deep vein thrombosis(DVT) and
pulmonary embolism(PE), retrievable inferior vena cava(IVC) filters have commonly
been used as an effective bridge to anticoagulation. However, we experienced
unexpected difficulty in endovascular retrieval of some IVC filters. Most
problems were due to endovascular treatment devices issues, filter intimal
migration, filter disintegration, filter-associated thrombosis, and right
atrium/ventricle migration. METHODS: Disposable biopsy forceps was used to engage
the filter hook and reform the shape of the filter struts. Endovascular retrieval
assisted by use of the biopsy forceps via a similar vein was effective and
provided a less-invasive, low cost method for removal of problematic IVC filters.
RESULTS: We described easily performed methods that uses disposable biopsy
forceps for the retrieval of IVC filters that are difficult to remove because of
filter hook migration into the caval wall. CONCLUSION: We developed an easily
performed method that uses intestine biopsy forceps for the retrieval of IVC
filter that are difficult to remove.
PMID- 27489652
TI - Endovascular treatment of arterio-ureteral fistulae with covered stents: Case
series and review of the literature.
AB - Arterio-ureteral fistulae are abnormal connections between an artery and the
ureter and carry a high mortality. We present two cases of arterio-ureteral
fistulae that presented with life-threatening hematuria. Both patients were
treated with endovascular covered stent placement.
PMID- 27489653
TI - Surgical repair of anomalous connection of the left coronary artery.
AB - An asymptomatic 10-year-old girl with anomalous connection of the left coronary
artery to the pulmonary artery underwent successful surgical repair to create a
two-artery coronary system with a coronary elongation technique using an
autologous pulmonary arterial wall flap. This technique facilitates direct and
tension-free coronary artery re-implantation.
PMID- 27489654
TI - "Cat Scratch Colon" and Cecal Barotrauma perforation during colonoscopy using CO2
insufflation.
AB - Cecal perforation due to barotrauma is an increasingly recognized complication of
colonoscopy when using room air for insufflation. CO2 is increasingly being
utilized for insufflation due to more rapid absorption compared to ambient air
and results in reduced post-procedural pain and flatulence. Use of CO2 is thought
to protect against barotrauma injury, and use of CO2 during endoscopy has not
previously been reported to cause barotrauma perforation during colonoscopy. We
present a case of cecal perforation secondary to barotrauma during routine
screening colonoscopy with CO2.
PMID- 27489655
TI - Surgical repair of large aortocaval fistula with limited shunt: Case report.
AB - A 67-year-old man was admitted with severe back pain and bilateral lower limb
swelling. Enhanced computed tomography showed an infrarenal abdominal aortic
aneurysm (92 * 75 mm(2)) and a short aortocaval fistula (7 mm). Immediately
afterward, circulatory collapse occurred, and the patient was rushed to the
operating theater. A much larger aortocaval fistula (22 * 35 mm(2)) than that
demonstrated by preoperative computed tomography was found and was repaired with
a Dacron patch while using two balloon-tipped catheters to control bleeding.
Then, the abdominal aortic aneurysm was replaced with a bifurcated graft. The
patient's postoperative course was uneventful. In this case, enhanced computed
tomography detected the aortocaval fistula, but could not assess its size
accurately. Successful surgical repair of an aortocaval fistula depends on early
accurate delineation of the fistula and prompt control of bleeding.
PMID- 27489656
TI - A novel mutation in the succinate dehydrogenase subunit D gene in siblings with
the hereditary paraganglioma-pheochromocytoma syndrome.
AB - Germline mutations in the succinate dehydrogenase complex subunit D gene are now
known to be associated with hereditary paraganglioma-pheochromocytoma syndromes.
Since the initial succinate dehydrogenase complex subunit D gene mutation was
identified about a decade ago, more than 131 unique variants have been reported.
We report the case of two siblings presenting with multiple paragangliomas and
pheochromocytomas; they were both found to carry a mutation in the succinate
dehydrogenase complex subunit D gene involving a substitution of thymine to
guanine at nucleotide 236 in exon 3. This particular mutation of the succinate
dehydrogenase complex subunit D gene has only been reported in one previous
patient in Japan; this is, therefore, the first report of this pathogenic
mutation in siblings and the first report of this mutation in North America. With
continued screening of more individuals, we will be able to create a robust
mutation database that can help us understand disease patterns associated with
particular variants and may be a starting point in the development of new
therapies for familial paraganglioma syndromes.
PMID- 27489657
TI - Effect of correction of hindfoot valgus deformity on ankle joint pain relief in
rheumatoid arthritis cases: A report of two cases.
AB - We often see painful ankle joint destruction with painful hindfoot valgus
deformity in rheumatoid arthritis. Our policy in such cases has been to first
correct the hindfoot deformity in the subtalar joint with fusion, but then ankle
joint pain has been observed. Two women with rheumatoid arthritis underwent
correction and fusion surgery for hindfoot valgus deformity. They had been using
wheelchairs because of severe pain in the ankle joint and hindfoot despite
extensive medical treatment. After surgery, both patients complained of no pain
in the hindfoot. Furthermore, dramatic pain reduction in the ankle joint was also
observed especially in a case without ankle joint instability. Consequently, the
patients could walk without any support. Correction of valgus hindfoot deformity
contributes to centralizing the weight-bearing line in the ankle joint, leading
to ankle joint pain relief. It appears possible to preserve the ankle joint
without additional ankle surgery even in rheumatoid arthritis cases, if ankle is
stable.
PMID- 27489658
TI - All that wheezes: A young infant with a mediastinal mass.
AB - Wheezing infants are frequently encountered in the emergency department.
Bronchiolitis is the most commonly seen cause. Radiographs are not recommended in
the routine management of bronchiolitis. We present the case of a young wheezing
infant with a mildly abnormal chest x-ray whose cystic hygroma caused life
threatening respiratory distress soon after he was admitted to the hospital.
PMID- 27489659
TI - Conservative management of broken guidewire: Case reports.
AB - Fractures of coronary guidewires during percutaneous coronary intervention within
a coronary vessel lumen are a rare but serious complication. There have been
several cases reported in the literature, some managed with surgical
intervention, others with medical therapy. We present two prospective cases from
our center. Both cases were managed successfully with medical therapy.
PMID- 27489660
TI - Bronchoscopic interventions with surfactant and recombinant human
deoxyribonuclease for acute respiratory distress syndrome-type respiratory
syncytial virus-pneumonia in moderately preterm infants: Case series.
AB - Atelectases, over-inflation of ventilated regions of the lung, and consecutive
pneumothoraces are life-threatening conditions in mechanically ventilated infants
with acute respiratory distress syndrome-type respiratory syncytial virus
pneumonia. The accumulation of viscous secretions secondary to impaired
mucociliary clearance in the more proximal parts of the bronchial tree is the
prerequisite for atelectases and also prevents the delivery of inhaled
medications to the more distal parts of the lung. Herein, we describe four
moderately premature infants with respiratory failure on mechanical ventilation,
displaying a total of 20 radiologically verified new atelectases that were
treated by bronchoscopic interventions with consecutive suctioning of secretions,
restoration of the surfactant film within the airways, and deposition of
recombinant human deoxyribonuclease at the first segment level of the bronchial
tree. On 13 occasions (65%), resolution of atelectases was proven by chest X-ray
and resulted in improved lung function. We conclude that these bronchoscopic
interventions may contribute to the restoration of the gas exchange area in
moderately premature infants with acute respiratory distress syndrome-type
respiratory syncytial virus-pneumonia.
PMID- 27489661
TI - Delayed pneumothorax after laparoscopic sigmoid colectomy in a patient without
underlying lung disease.
AB - We present an unusual case of a delayed pneumothorax occurring approximately 72 h
post-operatively in a patient without any underlying lung disease who had
undergone laparoscopic sigmoid colon resection. The patient was in her mid-40s
with a body mass index of 28.0 and had no history of smoking. Her spontaneous
pneumothorax manifested without any precipitating events or complications during
recovery. There was no evidence of any infectious process. There were no central
line attempts and all ports were placed intra-peritoneally, and there was no
evidence of any subcutaneous emphysema. One possible mechanism of injury that we
propose is barotrauma from an extended period of time in Trendelenburg position.
Notably, the only abnormal finding throughout the entire post-operative period
preceding the delayed pneumothorax was a PO2 desaturation the day before. This
case highlights the necessity to examine and investigate any desaturation post
operatively and deliberate its possible significance. Furthermore, it
demonstrates that, even during a normal recovery period for a patient without any
underlying lung disease or risk factors, spontaneous pneumothorax could still
develop in a delayed fashion multiple days post-operatively from a laparoscopic
procedure.
PMID- 27489662
TI - Hybrid endovascular and surgical approach for mycotic pseudoaneurysms of the
extracranial internal carotid artery.
AB - OBJECTIVES: Mycotic pseudoaneurysms of the extracranial internal carotid artery
are rare, and their management often represents a challenge, but treatment is
necessary due to the high risk of rupture and distal brain embolization. Systemic
antibiotics associated with open surgical excision of the infected tissues and
carotid reconstruction using autologous grafts are the treatment of choice. The
use of endovascular techniques still remains controversial in infective fields;
however, it can be an attractive alternative in high-risk patients or more often
as a "temporary" solution to achieve immediate bleeding control for a safe
surgical reconstruction. METHODS: We discuss the unusual case of an extracranial
right internal carotid artery mycotic pseudoaneurysm following methicillin
resistant Staphylococcus aureus infection, in a patient with poor general
conditions. RESULTS AND CONCLUSION: The lesion was successfully treated using a
hybrid endovascular and surgical procedure.
PMID- 27489663
TI - A case of non-paraneoplastic anti-N-methyl d-aspartate receptor encephalitis
presenting as a neuropsychiatric disorder.
AB - N-methyl d-aspartate receptor antibody encephalitis can often be a paraneoplastic
manifestation of occult malignancy such as ovarian teratoma and rarely teratoma
of mediastinum or testis and small cell lung carcinoma. We report a case of non
paraneoplastic anti-N-methyl d-aspartate receptor antibody-positive autoimmune
encephalitis in a young patient who presented with neuropsychiatric features and
made a very good recovery following treatment with intravenous immunoglobulin and
steroids. The case highlights the need for increased vigilance for the condition
in young females with or without a previous psychiatric history and emphasises
the need for a multidisciplinary approach in the management of this challenging
disorder with a good prognosis.
PMID- 27489664
TI - Four-month-old infant with intussusception presenting as altered mental status.
AB - OBJECTIVE: To remind pediatric care providers that an altered mental status can
be the only presenting symptom for intussusception, a life-threatening diagnosis.
METHOD: A case report that presents a unique presentation of intussusception: a 4
month old boy with neurological findings after a reported head injury.
CONCLUSION: Diagnosis of intussusception in the pediatric population is highly
dependent on its classical presenting signs and symptoms: sudden severe colicky
abdominal pain, vomiting, and an abdominal mass in children between 3 months and
6 years of age. Consider that an altered mental status can be the only presenting
symptom.
PMID- 27489665
TI - Submandibular approach and use of Ligasure((r)) system in a complex carotid
paraganglioma.
AB - Carotid paragangliomas are rare tumors of slow growth, progressive, and highly
vascularized; surgery is the chosen treatment, and most surgeons perform an
approach with a longitudinal cervicotomy. OBJECTIVE: We present a case of carotid
paraganglioma Shamblin III with skull base extension. METHODS: Submandibular
approach and vascular sealing device of the Ligasure((r)) system were used in the
surgery. RESULTS: We achieved complete resection using these adjunctive
techniques. CONCLUSIONS: The use of these adjunctive techniques can be useful to
manage large carotid body tumors.
PMID- 27489666
TI - An illustrative case of primary angiitis of the central nervous system.
AB - Primary angiitis of the central nervous system is a rare idiopathic vasculitis
affecting small- and medium-sized vessels, isolated to the brain, leptomeninges
and spinal cord. We report a case of biopsy-proven primary angiitis of the
central nervous system, displaying some atypical features. This case highlights
several key diagnostic and management issues of the disorder as well as its
potential heterogeneity.
PMID- 27489667
TI - Vitamin D and depression: A case series.
AB - INTRODUCTION: Over two-thirds of Canadians are deficient in vitamin D. Clinical
overlap can compound diagnosis of depression in vitamin D deficient individuals.
Citing high costs, the Ministry of Health has restricted routine vitamin D
screening and hence is not feasible. OBJECTIVES: The current case series is an
attempt to recognise the clinical overlap between depression and vitamin D
deficiency in order to avoid unnecessary antidepressant prescriptions and to
demonstrate the role of collaborative care in such patients. METHOD: After
appropriate ethics approval 62 patients from an outpatient clinic were screened
for the diagnosis of treatment resistant depression. Those who had predominant
somatic complaints were further screened for organic factors and those with
inadequate vitamin D levels were referred to family physicians for
supplementation with vitamin D. RESULTS: More than 50% were detected deficient in
vitamin D after our evaluation. They showed subjective improvement with vitamin D
supplements. No modification of antidepressants was needed. CONCLUSION: Vitamin D
deficiency should be suspected in depressed patients with prominent somatic
symptoms and their treatment resistance should be reconsidered to avoid
unnecessary exposure to mood stabilisers. Collaborating with primary care is
advocated. LIMITATION: Co-prescription of an antidepressant is a confounder in
our case series, and we propose more organised studies with objective rating
scales.
PMID- 27489668
TI - Venlafaxine augmentation with agomelatine in a patient with obsessive-compulsive
disorder and suicidal behaviors.
AB - Obsessive-compulsive disorder is a chronic and disabling condition that often
proves to be treatment resistant. Of the patients suffering from obsessive
compulsive disorder, 10%-27% may attempt suicide at least once in their life. We
report the case of a patient who presented severe obsessive-compulsive disorder
symptoms and attempted suicide ingesting 25 tablets of fluoxetine (20 mg). The
patient was treated with venlafaxine and agomelatine and showed improvement of
obsessive symptoms and suicidal ideation. Future studies are needed to
investigate this treatment regime in large cohorts of obsessive-compulsive
disorder patients with suicidal ideation.
PMID- 27489669
TI - Use of infrared thermography in children with shock: A case series.
AB - Shock is a complex clinical syndrome caused by an acute failure of circulatory
function resulting in inadequate tissue and organ perfusion. Digital infrared
thermal imaging is a non-invasive technique that can detect changes in blood
perfusion by detecting small changes in the temperature of the skin. In this
preliminary study, eight pediatric patients (five boys, three girls), ages
ranging from 6 to 14 years (average: 9.8 years), were admitted to the Intensive
Care Unit at "Dr. Ignacio Morones Prieto" Central Hospital; here, the patients
were examined using digital infrared thermal imaging. Patients in shock showed a
significant decrease in distal temperature (at least 7 degrees ), compared to
critically ill patients without shock. The latter group presented a skin
temperature pattern very similar to the one previously reported for healthy
children. The results show that infrared thermography can be used as a non
invasive method for monitoring the temperature in pediatric patients in intensive
care units in order to detect shock in its early stages.
PMID- 27489670
TI - Sudden post-traumatic sensorineural hearing loss reverted to normal by sneezing.
AB - An 11-year-old child with sudden post-traumatic sensorineural hearing loss
regained his hearing functions after sneezing. This case report is a first in
medical literature in describing recovery from hearing loss by sneezing. The
therapeutic implications of this rare case deserve further investigation.
PMID- 27489671
TI - Qigong program on insomnia and stress in cancer patients: A case series report.
AB - BACKGROUND: In recent years, the interest in Qigong as an alternative therapy has
grown following reports of its ability to regulate psychological factors in
cancer patients. This is a case series to evaluate the outcome measures of Qigong
when used as an adjunct to standard medical care to treat insomnia and stress in
cancer patients. PATIENTS AND METHODS: The Qigong program was applied to four
cancer patients with insomnia, stress, and anxiety. The program consisted of 30
min sessions involving exercise, patting of the 12 meridians, and spontaneous
breathing exercises three times a week for a period of 4 weeks. The Pittsburgh
Sleep Quality Index was measured as the primary outcome, while the Stress Scale,
the State-Trait Anxiety Inventory, and the Functional Assessment Cancer Therapy
General determined the secondary outcomes. Insomnia, stress, and anxiety levels
were examined weekly, while quality of life was examined on the first visit and
the last visit. RESULTS: The Pittsburgh Sleep Quality Index and Stress Scale
scores were reduced after conduct of the Qigong program. CONCLUSION: This study
could provide a better understanding of Qigong's influence on insomnia and stress
in cancer patients. However, a larger controlled trial should be conducted to
confirm these findings.
PMID- 27489672
TI - Disseminated cryptococcosis in a patient with HIV/AIDS at a teaching hospital in
Ghana.
AB - OBJECTIVE: To raise awareness of the existence of cryptococcal infections in
HIV/AIDS patients in Ghana. METHOD: Detailed postmortem gross and
histopathological analysis of an HIV/AIDS patient suspected to have cryptococcal
meningitis was carried out and histopathological findings correlated with
clinical findings. RESULTS: showed disseminated Cryptococcosis in an HIV/AIDS
patient which was confirmed with special stains. CONCLUSION: cryptococcal
infection occurs in HIV /AIDS patients in Ghanaian and when clinically suspected
the diagnosis should be pursued vigorously.
PMID- 27489673
TI - Aneurysm growth after late conversion of thoracic endovascular aortic repair.
AB - A 69-year-old man underwent thoracic endovascular aortic repair of a descending
aortic aneurysm. Three years later, he developed impending rupture due to
aneurysmal expansion that included the proximal landing zone. Urgent open surgery
was performed via lateral thoracotomy, and a Dacron graft was sewn to the
previous stent graft distally with Teflon felt reinforcement. Postoperatively,
four sequential computed tomography scans demonstrated that the aneurysm was
additionally increasing in size probably due to continuous hematoma production,
suggesting a possibility of endoleaks. This case demonstrates the importance of
careful radiologic surveillance after endovascular repair, and also after partial
open conversion.
PMID- 27489674
TI - A unique case of isolated, spontaneous, symptomatic celiac trunk dissection.
AB - Cases of isolated spontaneous celiac trunk dissections have been appearing in the
literature more recently with the increased availability of high-resolution
computerized tomography angiograms. We report a unique case of this entity. A 48
year-old woman presented with acute abdominal pain that radiated to the back and
worsened with breathing. This was diagnosed as a celiac trunk dissection by
computerized tomography angiogram. She was treated conservatively with
antihypertensive medications, anticoagulants, and opioid medication for pain
control.
PMID- 27489675
TI - Femorofemoral bypass allowed limb preservation after late diagnosis of left
common iliac artery thrombosis due to blunt trauma: A case report.
AB - OBJECTIVE: Acute common iliac artery occlusion which results from blunt abdominal
trauma is rare and potentially leads to a late diagnosis. METHODS: We report a
case of a 58-year-old patient who suffered a late diagnosed acute left common
iliac artery occlusion secondary to abdominal trauma. An emergency exploratory
laparotomy was performed to stop intra-abdominal bleeding, while his left limb
ischemia was not noticed until 32 h later and femorofemoral bypass was then
successfully performed for revascularization. Compartment syndrome was observed
postoperatively, and fasciotomy was performed promptly. The wound was temporarily
covered with Vaccum Sealing Drainage due to high skin tension. Patient underwent
skin-grafting after leg swelling subsided. RESULTS: The follow-up turned out that
these managements were valid in the preservation of the limb viability.
CONCLUSIONS: This case highlights the prudent recognition of the acute lower
extremity ischemia in the abdominal trauma and immediate remedy for acute iliac
artery occlusion after a late diagnosis.
PMID- 27489676
TI - Isolated fibrous dysplasia of the ethmoid sinus.
AB - Fibrous dysplasia is a benign fibro-osseous lesion progressing with one or more
bone involvements in the skeleton. Even though it is a benign tumor, it may
potentially transform into a malignant one. While the most frequently involved
zones in the head-neck zone include the maxilla, mandible, parietal, occipital,
and temporal zones, the involvement of the ethmoid bone is rather rare. This
article presents the case of a female patient who was diagnosed with fibrous
dysplasia in the right ethmoid sinus based on the paranasal computerized
tomography scan that was taken due to the symptoms of pain around the right eye,
pressure, and a feeling of being pushed.
PMID- 27489677
TI - Liver dysfunction and anti-thyroid therapy.
AB - Thioamides have been used in the management of hyperthyroidism for over 50 years.
Liver dysfunction is a rare but important side effect associated with their use.
Recently, cases of liver failure associated with propylthiouracil have prompted
the Federal Drug Administration to issue a Boxed Warning to the label of
propylthiouracil regarding its risk of potentially fatal liver injury and acute
liver failure in adults and children. Herein, we present a case to underline the
importance of recognising the similar potential for severe hepatic dysfunction
with the use of other thioamides.
PMID- 27489678
TI - Spontaneous development of neoplasms in severe combined immunodeficient mice.
AB - Severe combined immunodeficient (SCID) mice lack functional T and B cells. This
renders them useful for implantation of human cells. The absence of immune cells,
however, makes severe combined immunodeficient mice highly susceptible to
infections and spontaneous development of malignancies; 2 of 114 CB17/Icr
Prkdc(scid) /IcrIcoCrl severe combined immunodeficient mice aged 9 and 10 months
developed spontaneous acute leukaemia and thymic lymphoma. The differential
diagnosis of such an atypical lymphoid infiltrate includes 'leaky' severe
combined immunodeficient mice, thymic lymphoma and acute leukaemia. Until this
time, the link between the development of neoplasms in severe combined
immunodeficient mice and the mutation remains unclear.
PMID- 27489679
TI - Transumbilical glove port: A cost-effective method for single-incision
laparoscopic hepatectomy.
AB - OBJECTIVES: Emerging concepts of "reduced port surgery" have gained considerable
attention from laparoscopic surgeons, including the field of liver resection. To
date, 86 cases of single-incision laparoscopic hepatectomy (SILH) have been
reported, with commercially available access devices being used in most of these
cases. We report herein a use of homemade transumbilical glove port for SILH.
METHODS: A 39-year-old woman represented giant hepatic hemangioma (9-cm in size)
located at the left lateral segment (S2/3). Partial hepatectomy was performed by
the glove method via single port access with conventional laparoscopic bipolar
forceps, grasper and scissors without the need of any single-port specific
devices. RESULTS: The operative time was 77 minutes, and intraoperative blood
loss was 50 mL. The postoperative course was uneventful. CONCLUSIONS: Glove
method not only has significant advantages in terms of cost, but also is superior
in its versatility, allowing wider range of movements compared to conventional
access devices. Taking in consideration its cost effectiveness and versatility,
glove method may be a good option for SILH.
PMID- 27489680
TI - Angiojet thrombolysis and vena cava filter insertion in a case of a duplicated
inferior vena cava.
AB - OBJECTIVES: Duplication of the inferior vena cava (IVC) complicates
interventional procedures. This case report aims to shed light on this unusual
anomaly and the preoperative considerations necessary when treatment of venous
thromboembolism is undertaken. METHODS: An IRB approved case report of a 58 year
old woman presented emergently with right lower extremity phlegmasia due to
extensive thrombosis of her right iliofemoral and infrarenal portion of her
duplicated IVC. RESULTS: The patient underwent IVC filter placement and rheolytic
thrombectomy with thrombolysis using the Angiojet device followed by venoplasty
and stenting of the iliofemoral system and right IVC. Complete symptomatic and
radiographic resolution on duplex imaging was achieved at 1 year follow up.
CONCLUSIONS: With adequate preoperative awareness of IVC anomalies and treatment
options available satisfactory results can be achieved and complications
minimized for this unique patient population.
PMID- 27489681
TI - Endovascular repair of symptomatic carotid artery aneurysm with covered stent: A
case report and literature review.
AB - OBJECTIVES: Extracranial carotid artery true aneurysm is extremely uncommon, and
definite treatment has traditionally involved open surgical repair. Although
successful management of the internal carotid artery aneurysms using endovascular
stenting and embolization has recently been reported, only a limited number of
cases have been reported. METHODS: We present a case of symptomatic carotid true
aneurysm repaired with covered stent and coil embolization of the external
carotid artery. We also review the English literature and discuss the
epidemiology, causes, diagnosis, and management options of internal carotid
artery aneurysms. RESULTS: The patient did not have any complications, and was
discharged home on the postoperative day 1 in stable condition. CONCLUSION: Our
report suggests that endovascular procedure is feasible in the treatment of
extracranial carotid artery aneurysms.
PMID- 27489682
TI - Management of primary iliopsoas abscess in an immunocompetent patient followed by
streptococcal toxic shock syndrome: A case report.
AB - OBJECTIVES: Clinical diagnosis of iliopsoas abscess can be challenging, as this
pathology often presents without obvious focal findings. Iliopsoas abscess should
thus be a differential diagnosis for patients presenting with fever of unknown
origin. PATIENT AND METHODS: A 62-year-old healthy Japanese man showed primary
iliopsoas abscess of Klebsiella pneumoniae complicated by shock after a complete
course of treatment for streptococcal toxic shock syndrome. Successful treatment
was achieved with culture-driven antibiotic selection and delayed drainage.
RESULTS: This case demonstrates the importance of identifying the causative
microorganisms in iliopsoas abscess to guide therapy. The standard treatments for
iliopsoas abscess are antibiotics and drainage of the abscess. Management of this
case included successful antibiotic use along with delayed drainage. CONCLUSION:
This case report advances the knowledge on the etiology of iliopsoas abscess and
sheds light on the need for scientific development of a treatment strategy.
PMID- 27489683
TI - Unrestricted access to medical case reports.
PMID- 27489684
TI - A case of transient hypothermia after trans-lamina terminalis and third ventricle
clipping of an extremely high-position basilar tip aneurysm.
AB - Reports on the trans-lamina terminalis and trans-third ventricular approach are
rare. The risk associated with this approach is unknown. After an unsuccessful
endovascular surgery, we performed direct surgical clipping via the third
ventricle on a 78-year-old woman presenting with an extremely high-positioned,
ruptured basilar tip aneurysm. She experienced transient hypothermia for 5 days,
and it was considered that this was due to hypothalamic dysfunction. It is
necessary to recognize that there is the potential for hypothermia after surgery
via the lamina terminalis and third ventricle, even though the mechanisms of
hypothalamic thermoregulation are still unclear.
PMID- 27489685
TI - Subclavian artery stenosis caused by a prominent first rib.
AB - Thoracic outlet syndrome is a mechanical space problem in which the brachial
plexus and/or subclavian vessels are compressed. Arterial compression is least
common and almost always associated with a bony anomaly. We present a case of a
49-year-old woman with a prominent first rib which caused a subclavian artery
stenosis. There are many options for subclavian artery repair through open
surgery. In high-risk patients, minimal invasive techniques are favorable. To
date, few case reports exist on an endovascular artery repair combined with open
first rib resection. While long-term follow-up will be necessary, our preliminary
results seem promising.
PMID- 27489686
TI - Therapeutic hypothermia after cardiac arrest in Long QT syndrome: Could it be an
adjunctive treatment to prevent dysrhythmias?
AB - Therapeutic hypothermia has been used for neuroprotection following cardiac
arrest presenting with ventricular tachycardia or ventricular fibrillation
regardless of underlying cause. Long QT syndrome is a cause for polymorphic
ventricular tachycardia, and we know that therapeutic hypothermia increases the
QT interval. We managed a 27-year-old woman, who was 10 weeks post-partum, who
collapsed secondary to ventricular fibrillation at home. Bystander
cardiopulmonary resuscitation was started with successful resuscitation after a
rescue shock from paramedics. On hospital admission, her computerised tomography
head, computerised tomography pulmonary angiogram and echocardiography did not
show any abnormality. Her baseline electrocardiogram showed prolonged QTc
interval of 504 ms without ischaemic changes. After intubation and ventilation,
she was treated with therapeutic hypothermia for 48 h. She had a further episode
of polymorphic ventricular tachycardia requiring rescue shock just prior to
starting therapeutic hypothermia in hospital. No dysrhythmias occurred during
therapeutic hypothermia, although the QTc further increased. After stopping the
therapeutic hypothermia, she had two further ventricular tachycardia episodes.
After commencement of beta blockers, she remained free of arrhythmias, and an
implantable cardioverter defibrillator was implanted, she has recovered without
any neurological deficit. Ventricular dysrhythmias caused by prolongation of the
QT interval during or after therapeutic hypothermia are not well understood.
There has been a report of a patient also having ventricular dysrhythmia 2 h
after re-warming post therapeutic hypothermia and also a report of arrhythmia
free period during therapeutic hypothermia in a long QT syndrome patient; both
these features are present in our patient. Re-warming is not usually known to
cause any arrhythmias; however, it could be a problem in those with long QT
syndrome. Whether therapeutic hypothermia has a place in helping to control
ventricular dysrhythmias needs further study.
PMID- 27489687
TI - Theophylline toxicity leading to suicidal ideation in a patient with no prior
psychiatric illness.
AB - Suicidal behavior is a common psychiatric emergency and is associated with
psychiatric illness and history of prior suicide attempts. Neuropsychiatric
manifestations related to theophylline toxicity are well described in literature.
We report a case of theophylline toxicity manifesting as suicidal ideation in a
patient with no prior psychiatric illness.
PMID- 27489688
TI - Pre-operative endostent placement to allow the complete and safe resection of a
recurrent tumor that had tightly adhered to the subclavian artery: A case report.
AB - Radiation and tumor infiltration confer a high risk of bleeding on surgical
removal of tumor. We report on the case of a 42-year-old woman with a recurrent
occult subclavian tumor in her right breast. Computed tomography revealed
enhanced tumor adhesion to the subclavian artery at the infraclavicular lymph
node. No other metastases were detected. We pre-operatively performed stenting of
the right subclavian artery, and the tumor was resected completely and safely.
PMID- 27489689
TI - Communication failures during clinical handovers lead to a poor patient outcome:
Lessons from a case report.
AB - In the emergency department, communication failures occur in clinical handover
due to the urgent, changing and unpredictable nature of care provision. We
present a case report of a female patient who was assaulted, and identify how
various factors interacted to produce communication failures at multiple clinical
handovers, leading to a poor patient outcome. Several handovers created many
communication failures at diverse time points. The bedside medical handover
produced misunderstandings during verbal exchange of information between
emergency department consultants and junior doctors, and there was
miscommunication involving plastic registrars. There was a failure in adequately
informing the general practitioner and the patient relating to follow-up care
after discharge. Deficiencies of communication occurred with conveying changes in
an investigative report. Communication could be improved by dividing the conduct
of handover in a quiet room and at the bedside, ensuring multiple sources of
information are used and encouraging role-modelling behaviours for junior
clinicians.
PMID- 27489690
TI - Use of a topical anhydrous silicone base containing fatty acids from pracaxi oil
in a patient with a diabetic ulcer.
AB - OBJECTIVES: The treatment of diabetic ulceration of the lower extremities is a
complicated task due to the nature of the ulcer and potential underlying
comorbidities. This report describes the case of a 61-year-old male patient with
Type 2 Diabetes who presented with an ulcerative leg wound. The objective of this
study was to evaluate the outcome of a topical compounded treatment. METHODS: The
patient applied a compounded medicine containing 2% mupirocin in a topical
anhydrous silicone base containing fatty acids from pracaxi oil directly to the
ulcer for 63 days, 3 times daily. This regimen was supplemented with exercise and
an additional compounded medicine applied to the wound margins in order to
increase circulation. RESULTS: By the end of the application period, the
patient's ulcer was fully closed. CONCLUSION: A topical anhydrous silicone
compounding base containing fatty acids from pracaxi oil may be useful in the
treatment of patients with diabetic ulcers.
PMID- 27489691
TI - Fatal persistent methicillin-resistant Staphylococcus aureus bacteremia and
vascular graft infections complicated with the formation of multiple abscesses
despite aggressive medical therapy.
AB - A 40-year-old man underwent ascending aorta replacement for an acute type A
aortic dissection. After the operations, methicillin-resistant Staphylococcus
aureus was identified in sputum and blood cultures. Although anti-methicillin
resistant Staphylococcus aureus drugs were administered, most of the intermittent
blood cultures remained positive. The focus of methicillin-resistant
Staphylococcus aureus infection was not evident in the early stages, and no
specific symptoms such as abscess or endocarditis were observed. However,
abscesses in the brain, mediastinum and spleen were found 3 years after the
operation. The minimum inhibitory concentration of vancomycin gradually increased
from 1 to 4 ug/mL during the course of treatment. This case provides evidence for
a potential role of combination therapy.
PMID- 27489692
TI - Acute embolic occlusion of the right common iliac artery after revision total hip
arthroplasty treated with catheter-directed thrombolysis and balloon angioplasty:
A case report.
AB - METHODS: A 63-year-old woman with atrial fibrillation presented clinical symptoms
and signs of acute ischemia in the right lower extremity on the 17th
postoperative day after revision total hip arthroplasty of the left hip for
aseptic loosening of femoral component. Aspirin was discontinued 7 days before
surgery. Both computed tomography angiography and digital subtraction angiography
demonstrated complete occlusion of the right common iliac artery. An emergency
catheter-directed thrombolysis with urokinase combined with balloon angioplasty
was performed to obtain complete patency of the right common iliac artery.
RESULTS: The patient received anticoagulation and antiplatelet therapy
postoperatively and was fine at the 2-year follow-up. CONCLUSIONS: This case
demonstrated that catheter-directed thrombolysis combined with balloon
angioplasty could be an efficacious, minimally invasive approach for the
treatment of acute embolic occlusion of the common iliac artery. Preoperative
anticoagulation for patients undergoing total hip arthroplasty with long-term use
of aspirin for atrial fibrillation needs further investigation.
PMID- 27489693
TI - Inferior vena cava filter misplacement in the right atrium and migration to the
right ventricle followed by successful removal using the endovascular technique:
A case report and review of the literature.
AB - Inferior vena cava filters are effective for preventing the passage of thrombi
into the pulmonary arteries in patients with pulmonary embolism and deep vein
thrombosis. These filters are indicated in patients with contraindications to
anticoagulant therapy or in patients with recurrent acute pulmonary embolism
despite the administration of anticoagulant therapy. However, the occurrence of
filter-related complications, such as filter migration to the heart, has been
increasing. Herein, we report a case of OptEase inferior vena cava filter
misplacement in the right atrium. Although the filter migrated to the right
ventricle, it was successfully removed and repositioned in the inferior vena cava
using endovascular techniques. Unfortunately, moderate tricuspid regurgitation
developed, due to the damage to the tricuspid valve that was caused by the
procedure. We have also reviewed the relevant literature and discussed the
possible strategies for managing cases of filter migration to the heart and
preventing filter misplacement.
PMID- 27489694
TI - First human case of avian influenza A (H5N6) in Yunnan province, China.
AB - OBJECTIVE: To report clinical, virological, and epidemiological features of the
first death caused by a H5N6 avian influenza virus in Yunnan Province, China.
METHOD: The case was described in clinical expression, chest radiography, blood
test and treatment. Real-time RT-PCR was used to detect H5N6 virus RNA in
clinical and environment samples. Epidemiological investigation was performed
including case exposure history determinant, close contacts follow up, and
environment sample collection. RESULTS: The patient initially developed sore
throat and coughs on 27 January 2015. The disease progressed to severe pneumonia,
multiple organ dysfunction syndrome, and acute respiratory distress syndrome. And
the patient died on 6 February. A highly pathogenic avian influenza A H5N6 virus
was isolated from the tracheal aspirate specimen of the patient. The viral genome
analyses revealed that the H5 hemmagglutinin gene belongs to 2.3.4.4 clade.
Epidemiological investigation showed that the patient had exposure to wild bird.
All close contacts of the patient did not present the same disease in seven
consecutive days. A high H5 positive rate was detected in environmental samples
from local live poultry markets. CONCLUSION: The findings suggest that studies on
the source of the virus, transmission models, serologic investigations, vaccines,
and enhancing surveillance in both humans and birds are necessary.
PMID- 27489695
TI - Phlegmonous gastritis secondary to superior mesenteric artery syndrome.
AB - We herein report a case of phlegmonous gastritis secondary to superior mesenteric
artery syndrome. An 80-year-old woman visited the hospital emergency department
with the chief complaints of epigastric pain and vomiting. She was hospitalized
urgently following the diagnosis of superior mesenteric artery syndrome based on
abdominal computed tomography findings. Conservative therapy was not effective,
and phlegmonous gastritis was diagnosed based on the findings of upper
gastrointestinal endoscopy and biopsy performed on the 12th day of the disease.
Undernutrition and reduced physical activity were observed on hospital admission,
and proactive nutritional therapy with enteral nutrition was started. An upper
gastrointestinal series, performed approximately 1 month later, confirmed the
persistence of strictures and impaired gastric emptying. Because conservative
therapy was unlikely to improve oral food intake, open total gastrectomy was
performed on the 94th day of the disease. Examination of surgically resected
specimens revealed marked inflammation and fibrosis, especially in the body of
the stomach. Following a good postoperative recovery, the patient was able to
commence oral intake and left our hospital on foot approximately 1 month after
surgery.
PMID- 27489696
TI - Warning leak of intracranial aneurysm masquerading as sinus node dysfunction: A
case report.
AB - We describe the successful endovascular repair of an intracranial aneurysm
causing subarachnoid hemorrhage in a 62-year-old man, who was initially diagnosed
and treated as a case of symptomatic sinus bradycardia. The aim of this report
and following discussion is to discuss the subtle warning signs of intracranial
aneurysm that may masquerade as sinus node dysfunction.
PMID- 27489697
TI - Total laparoscopic retrieval of inferior vena cava filter.
AB - While there is some local variability in the use of inferior vena cava filters
and there has been some evolution in the indications for filter placement over
time, inferior vena cava filters remain a standard option for pulmonary embolism
prophylaxis. Indications are clear in certain subpopulations of patients,
particularly those with deep venous thrombosis and absolute contraindications to
anticoagulation. There are, however, a variety of reported inferior vena cava
filter complications in the short and long term, making retrieval of the filter
desirable in most cases. Here, we present the case of a morbidly obese patient
complaining of chronic abdominal pain after inferior vena cava filter placement
and malposition of the filter with extensive protrusion outside the inferior vena
cava. She underwent successful laparoscopic retrieval of her malpositioned
inferior vena cava filters after failure of a conventional endovascular approach.
PMID- 27489698
TI - Henoch-Schonlein purpura antecedent to Crohn's disease.
AB - We report a 13-year-old youth who initially presented with the typical rash of
Henoch-Schonlein purpura followed a month later by a nephrotic syndrome and
hematuria. Renal biopsy revealed crescentic IgA nephropathy. The patient was
aggressively treated with steroids leading to a remission of his nephrotic
syndrome. Three years after his initial presentation, he developed bloody
diarrhea and Crohn's disease was diagnosed.
PMID- 27489699
TI - Use of the Wallstent for infrapopliteal arterial disease and varying vessel
diameters.
AB - There is little description of the Wallstent to treat infrapopliteal arterial
disease. This may be a viable option due to its high conformability and ability
to elongate in vessels of varying diameters. This case report highlights its use
in this clinical situation.
PMID- 27489700
TI - Steam-deformed Judkins-left guiding catheter with use of the GuideLiner((r))
catheter to deliver stents for anomalous right coronary artery.
AB - OBJECTIVE: Percutaneous coronary intervention for anomalous right coronary artery
(RCA) originating from the left coronary cusp is challenging because of our
current inability to coaxially engage the guiding catheter. METHODS: We report a
case of an 88-year-old woman with non-ST segment elevation myocardial infarction,
with an anomalous RCA origin. Using either the Judkins-Left catheter or Amplatz
Left catheter was difficult because of RCA ostium tortuosity. Thus, we used steam
to deform the Judkins-Left catheter, but back-up support was insufficient to
deliver the stent. RESULTS: We used GuideLiner(r), a novel pediatric catheter
with rapid exchange/monorail systems, to enhance back-up support. CONCLUSIONS: We
were able to successfully stent with both the deformed Judkins-Left guiding
catheter and GuideLiner(r) for an anomalous RCA origin.
PMID- 27489701
TI - Multiple endovascular aortic aneurysm repair graft failures and re-interventions
over 15 years.
AB - Re-intervention on abdominal aortic aneurysm treated by endovascular aortic
aneurysm repair for complications such as endoleak, graft migration, and graft
failure is relatively common. However, re-do endovascular aortic aneurysm repair
can be complex, as the failed graft still resides within the vessel. In addition,
some re-do endovascular aortic aneurysm repairs call for an advanced custom
graft, which can further increase the complexity and technical skill required. We
describe a case of a 15-year-old endovascular aortic aneurysm repair originally
implanted in a 71-year-old man, followed by three separate complications
requiring intervention. We describe important procedural decisions taken into
consideration when presented with failure of an older graft.
PMID- 27489702
TI - Successful embolization and long-term follow-up of a rare neonatal diaphragmatic
hemangioma.
AB - BACKGROUND: Congenital hemangioma of the diaphragm is an extremely rare disease
in childhood. METHODS: We report a newborn presenting with progressive
respiratory distress and massive right hydrothorax due to congenital
diaphragmatic hemangioma, requiring sustained ventilation support and chest
drainage. The angiography revealed that the giant diaphragmatic hemangioma was
supplied by the right internal thoracic, inferior diaphragmatic, and intercostal
arteries. The selective embolization of the main feeding vessels was successfully
achieved using the Embosphere particulates. RESULTS: The clinical long-term
follow-up demonstrated the resolution of the symptoms, pleural effusion, and
nearly complete regression of the hemangioma at 18 months of age. CONCLUSION:
Transcatheter embolization can provide an efficient therapy for symptomatic
diaphramatic hemangioma.
PMID- 27489703
TI - Variceal bleeding caused by oesophageal varices: A manifestation of
hepatocellular carcinoma in a 17-year-old girl.
AB - The authors present the rare case of a 17-year-old girl referred to the medical
assessment unit following a large upper gastrointestinal haemorrhage. On further
evaluation, she was found to have a primary hepatocellular carcinoma with
extensive metastases. In our patient, the tumour was deemed incurable by
resection, liver transplantation or percutaneous treatment. She underwent
palliative chemotherapy and passed away 11 months following presentation.
PMID- 27489704
TI - Endovascular management of early-onset post-nephrectomy renal arteriovenous
fistula: A report of two cases.
AB - PURPOSE: Here, we report two cases of early-onset post-nephrectomy renal
arteriovenous fistula who were successfully managed by implantation of patent
ductus arteriosus occluders. CASE REPORT: Both patients were female, aged 38 and
36 years. They received left renal nephrectomy 9 and 6 months, respectively, with
a complaint of chest congestion and dyspnea before admitting to our center.
Computed tomographic angiography revealed a huge arteriovenous fistula of the
left renal pedicle with a renal venous aneurysm in both patients. The fistulas
were isolated by implanting patent ductus arteriosus occluders in the renal
artery stumps. Clinical symptoms disappeared after intervention. Computed
tomographic angiography confirmed the effectiveness of the occluders during
follow-up time. The venous aneurysms shrank to normal size. CONCLUSION: Our
experience indicates that post-nephrectomy renal arteriovenous fistula can
present as an early complication which can be efficiently managed by endovascular
occlusion of the arterial stump by patent ductus arteriosus occluder.
PMID- 27489705
TI - Ornidazole-induced ataxia in an Indian woman: A case report.
AB - The nitroimidazole group of antibiotics like metronidazole have been reported to
cause cerebellar ataxia as a rare side effect. Ornidazole, the newest derivative
of this class, has a long half life and is very rarely known to cause cerebellar
ataxia. Here, we report a 61-year-old patient who developed ataxia due to
ornidazole to highlight an unusual adverse event that improved rapidly after
discontinuation of the offending drug.
PMID- 27489706
TI - High-grade primary myxoid lung sarcoma presenting as recurrent hemorrhagic
pleural effusions in a young woman.
AB - Primary lung sarcomas are rare but aggressive tumors accounting for less than
0.5% of all lung tumors. The diagnosis of primary lung sarcoma should only be
considered after exclusion of other sites. A 32-year-old female presented with
recurrent hemorrhagic pleural effusions, shortness of breath and persistent
cough. Pleural effusion was drained twice, and each time its analysis was normal.
Patient developed atelectasis of left lung with hemothorax for which she
underwent video-assisted thoracoscopic surgery. A large mass was found
compressing the entire lower lobe of left lung with extension into mediastinum,
the biopsy of which showed myxoid sarcoma. The tumor was inoperable and options
of chemotherapy or radiotherapy were discussed with the patient. Primary lung
sarcoma can rarely present with recurrent hemorrhagic pleural effusion. A high
degree of suspicion is required for early diagnosis as large hemothorax on
computed tomography or chest X-ray may obscure lung mass and make its diagnosis
difficult.
PMID- 27489707
TI - Penetrating retro-orbital foreign body - large glass shards: A maxillofacial
surgery case report.
AB - OBJECTIVES: This case report looks at a 53-year-old patient who had suffered a
penetrating foreign body injury to the retro-orbital space and the surgical
approach taken to remove the large glass fragments found and to correct the
damage caused. Having fallen while holding a drinking glass, this patient
suffered multiple laceration injuries to the maxillofacial region upon the glass
shattering in contact with the face. However, unbeknownst to the patient, several
glass fragments became embedded in the retro-orbital space, and this was only
detected on presentation 2 days post-injury with unusual symptoms of sharp,
sudden pain elicited on extreme gaze as well as ocular motility restriction.
METHODS: This embedded foreign body required a creative surgical approach to
remove it involving gaining access to the retro-orbital space via a superior
approach and cautiously following the path the glass shards took upon entry, all
the way to the posterior aspect of superior rectus. Intra-operative radiographic
guidance was required due to the restriction of operating within this space and
particularly when removing glass fragments distal to superior rectus. RESULTS AND
CONCLUSION: The patient recovered well and experienced an immediate improvement
in ocular motility with a return to relative normality over the next few months.
PMID- 27489708
TI - Duodenal neuroendocrine tumor and the onset of severe diabetes mellitus in a US
veteran.
AB - OBJECTIVE: Neuroendocrine tumors are neoplasms derived from endocrine cells, most
commonly occurring in the gastrointestinal tract. Duodenal neuroendocrine tumors
are rare tumors averaging 1.2-1.5 cm, and most are asymptomatic. Common
presentation is abdominal pain, upper gastrointestinal bleed, constipation,
anemia, and jaundice. METHODS: An adult, Black, male patient with newly diagnosed
diabetes mellitus presented to the emergency department with elevated liver
function test and fatigue. RESULTS: Magnetic resonance cholangiopancreatography
demonstrated a large obstructing mass (3.6 cm * 4.4 cm * 3 cm) within the second
and third portions of the duodenum at the ampulla. Esophagogastroduodenoscopy
demonstrated an ulcerated duodenal mass that was biopsied. Immunohistochemical
stains were positive for synaptophysin, chromogranin B, and CK7. Chromogranin A
was in normal range. Post-Whipple procedure demonstrated a 5.5 cm * 4.1 cm * 2.9
cm duodenal mass with invasion of the subserosal tissue of the small intestine, a
mitotic rate of 2 per high-power field, and antigen Ki-67 of 2%-5%. CONCLUSION:
This case raises the question as to if the patient developed diabetes mellitus
due to the tumor size and location or if the new onset of diabetes was
coincidental. This case also demonstrates the importance of a proficient history
and physical.
PMID- 27489709
TI - Myeloid sarcoma of submandibular salivary gland.
AB - OBJECTIVE: To report a rare case of a myeloid sarcoma of submandibular salivary
gland. METHODS: A 65-year-old woman with a history of successfully treated
myelodysplastic syndrome, presenting with periodic painful swelling of her right
submandibular area. RESULTS: Physical evaluation, ultrasound and CT scan revealed
the presence of a 3-cm mass contiguous to the submandibular salivary gland. A
core needle biopsy confirmed the diagnosis of myeloid sarcoma. Bone marrow biopsy
was still showing complete remission and the submandibular gland was the only
extramedullary site involved. The patient was submitted to chemotherapy.
CONCLUSION: Myeloid sarcoma is a rare extramedullary neoplasm. It can virtually
involve any anatomic site, but it usually involves lymph nodes, paranasal
sinuses, skin, soft tissue and periostium. Myeloid sarcomas of salivary glands
are very rare and ENTs should be aware of this disease in order to include it in
the differential diagnosis of a solitary neck mass.
PMID- 27489710
TI - A case of anomalous coronary artery origin: The role of computerised tomography.
AB - OBJECTIVE: To illustrate the utility of CT coronary angiography in the assessment
of patients with anomalous coronary arteries. METHODS: A 65-year-old woman who
presented with a clinical history of unstable angina was investigated with both
computerised tomography and invasive coronary angiography. RESULTS: Coronary
angiography demonstrated aberrant coronary arteries all arising from separate
ostia from the right coronary cusp. Computerised tomography coronary angiography
was required to confirm the course of the aberrant coronary arteries in relation
to other cardiovascular structures. CONCLUSIONS: This case illustrates the
important role of computerised tomography coronary angiography and that early use
might avoid the need for invasive coronary angiography.
PMID- 27489711
TI - Rhinogenic intracranial complication with postoperative frontal sinus pyocele and
inverted papilloma in the nasal cavity: A case report and literature review.
AB - We report a patient who had rhinogenic intracranial complication with
postoperative frontal sinus pyocele and inverted papilloma in the nasal cavity. A
72-year-old woman had undergone surgery for frontal sinusitis via external
incision at another hospital 13 years previously. Left-sided hemiparesis appeared
in the patient and gradually worsened. Five days later, she exhibited
disorientation, abnormal behavior, poor articulation, and difficulty in standing.
Therefore, she was taken to the neurosurgery department by ambulance. An
extensive frontal sinus pyocele was suspected, and a cerebral abscess and edema
of the frontal lobe were observed on magnetic resonance imaging. After
antibiotics, steroid and glycerol were administered for a few weeks;
disorientation and left hemiparesis improved. Next, craniotomy for complete
removal of the brain abscess by neurosurgeons and endoscopic endonasal surgery by
otolaryngologists were carried out at the same surgery. From the analysis of the
pathological mucosa sample taken from the right ethomoidal sinus during surgery,
an inverted papilloma was diagnosed. The patient completely recovered and is
currently receiving follow-up examination. Regarding rhinogenic intracranial
complications, ascertaining clinical condition in order to determine the need for
either immediate radical surgery, or for curative surgery after waiting for
improvement of the overall body condition by conservative management, is still
needed.
PMID- 27489712
TI - Acute myocardial infarction in a young athlete: Optical coherence tomographic
features of the culprit lesion.
AB - OBJECTIVES: We report on a young male athlete who suffered from acute myocardial
infarction immediately after a vigorous training. METHODS: A comprehensive
optical coherence tomographic investigation of the culprit coronary artery was
performed after the combined mechanical and pharmacological thrombus removal.
RESULTS AND CONCLUSION: The imaging discovered a tear at the junction of the non
obstructive, largely fibrotic plaque with the normal arterial wall. This exertion
related vessel damage resulted in a dynamic thrombosis that almost completely
occluded the culprit artery. As the vessel obstruction was not considered flow
limiting, the stent implantation was not required and the patient was discharged
on the double antiplatelet therapy and statin.
PMID- 27489713
TI - Mediastinal mass diagnosed by endobronchial ultrasound as recurrent
hepatocellular carcinoma in a post-liver transplantation patient.
AB - OBJECTIVE: We presented a rare case of recurrent hepatocellular carcinoma after
liver transplant manifested as an isolated mediastinal mass. METHODS: A 62-year
old man was referred for evaluation of atypical chest pain and abnormal finding
of a computed tomography of the chest. He had history of chronic hepatitis C
liver cirrhosis and hepatocellular carcinoma underwent orthotopic liver
transplant as a curative treatment three years earlier. RESULTS: The computed
tomography of the chest demonstrated paratracheal mediastinal lymphadenopathy. He
subsequently underwent endobronchial ultrasound with transbronchial needle
aspiration (EBUS-TBNA). The right paratracheal lymph node station 4R was sampled.
Rapid on-site cytology evaluation demonstrated recurrent metastatic
hepatocellular carcinoma. CONCLUSION: Pulmonologist should be cognizant of
diagnostic utility of EBUS-TBNA in this clinical setting as more transplant
patients on immunosuppressive medications with enlarged mediastinal
lymphadenopathy of unknown origin will be referred for further evaluation.
PMID- 27489714
TI - Zotarolimus-eluting stent fracture at initial implantation diagnosed with
StentBoost.
AB - Stent fracture is a rare complication of drug-eluting stent implantation with a
reported rate of 0.84%-3.2% in various clinical studies with first-generation
drug-eluting stents and 29% in autopsy studies. Sirolimus-eluting stents with
their closed cell design were reported to be more prone to fracture compared to
paclitaxel-eluting stents. Other risk factors for stent fracture are multiple
stenting, longer stent length, chronic renal failure, right coronary artery
intervention, and a higher maximal inflation pressure. The role of angiography in
diagnosing stent fracture is limited, a fact also questioning the reliability of
angiographic data. Image enhancement techniques like StentBoost are widely
available in new-generation angiography systems and are used to assess stent
expansion, overlap size, or to localize the postdilation balloon. Here, we report
a case of zotarolimus-eluting stent fracture at initial implantation diagnosed
with StentBoost.
PMID- 27489715
TI - Incidental finding of a huge ovarian serous cystadenoma in an adolescent female
with menorrhagia.
AB - Pelvic tumors in adolescent females are very uncommon. While the most common
presentation is pelvic discomfort, we report the case of a 14-year-old female
presenting with menorrhagia which is an unusual initial complaint for a large
pelvic tumor. Adolescent females who present with heavy menstrual bleeding
initially undergo assessment to rule out a bleeding disorder. In this case,
careful history and physical examination helped in making a quick diagnosis and
management. Ultrasound of abdomen showed a huge cystic mass due to serous
cystadenoma of the ovary.
PMID- 27489716
TI - Post-biliary sphincterotomy bleeding despite covered metallic stent deployment.
AB - OBJECTIVES: Several endoscopic techniques have been proposed for the management
of post-sphincterotomy bleeding. Lately, self-expandable metal stents deployment
has gained popularity especially as a rescue therapy when other endoscopic
techniques fail. METHODS-RESULTS: We report the case report of a massive post
sphincterotomy bleeding in a patient with a self-expandable metal stent in the
biliary tree. Despite the presence of a correctly positioned self-expandable
metal stent, a new endoscopic session was required to control the bleeding.
CONCLUSIONS: Self-expandable metal stent may be useful to manage post-endoscopic
sphincterotomy bleeding. However, up to now there is no specifically designed
self-expandable metal stent for such complication. Large new designed self
expandable metal stent may be a useful tool for biliary endoscopist.
PMID- 27489717
TI - Endovascular stent-graft repair of spontaneous aorto-caval fistula secondary to a
ruptured abdominal aortic aneurysm: An emergency management of hostile anatomy.
AB - OBJECTIVES: Although endovascular aneurysm repair of aorto-caval fistula offers a
safe and efficient approach compared to traditional open repair, endovascular
techniques for the treatment of aorto-caval fistula with ruptured abdominal
aortic aneurysms in emergency circumstance are not well established. This study
aims to evaluate the effect of endovascular repair of aorto-caval fistula of a
patient with ruptured abdominal aortic aneurysm and hostile anatomy. METHODS: we
report a case of an aorto-caval fistula endovascular repaired in a 78-year-old
male using a hybrid stent-graft technique. RESULTS: The patient had an uneventful
recovery and CTA follow up showed no sign of ACF or any endoleak. CONCLUSION:
This case highlights ACF might be managed by composite endograft implantation
with careful and solid sealing of anchoring zones on the two sides.
PMID- 27489719
TI - Ambiguous presentations of pulmonary epithelioid hemangioendothelioma: Two case
reports of a rare pulmonary malignancy.
AB - Pulmonary epithelioid hemangioendothelioma is an uncommon lung malignancy of
endothelial origin. Besides demonstrating unpredictable presentation features and
prognosis, the paucity of established treatment guidelines remains a challenge in
managing these patients. We present two patients. The first patient presented
with chronic productive cough over 1-year duration. He was initially diagnosed
and showed partial response to treatment for cardiac failure. A persistent right
upper zone consolidation on chest radiograph prompted further investigations
which revealed the diagnosis of pulmonary epithelioid hemangioendothelioma. The
second patient presented with right-sided hemiparesis for 1-month duration.
Initial computer tomography scan of the brain showed findings of distant
metastatic foci. Subsequent investigations revealed pulmonary epithelioid
hemangioendothelioma as the primary lesion. Both patients succumbed without any
treatment due to rapid progression of the disease. We believe that pulmonary
epithelioid hemangioendothelioma is undoubtedly rarely reported in south-east
Asia region. In these two case reports, the patients were diagnosed in west and
east Malaysia, respectively, in the same year (2015). Both cases highlight the
increasing prevalence of pulmonary epithelioid hemangioendothelioma. We postulate
that this could possibly be secondary to the advancement in diagnostic
capabilities and improved healthcare facilities available in this region. Late
presentation of pulmonary epithelioid hemangioendothelioma generally results in
grave prognosis. Further investigations are required to elucidate the nature of
progression and therapeutic options for patients with pulmonary epithelioid
hemangioendothelioma.
PMID- 27489718
TI - Delayed presentation of a carotid pseudoaneurysm following penetrating neck
trauma.
AB - OBJECTIVE: Penetrating carotid trauma in a hemodynamically stable patient
invariably presents with a pseudoaneurysm on initial imaging. Although extremely
rare, delayed pseudoaneurysm formation has been reported. The purpose of this
paper is to define this rare entity and propose a diagnostic and treatment plan.
METHODS: We present a case of delayed presentation of carotid pseudoaneurysm
following penetrating neck trauma. A systematic review of the literature was
performed. RESULTS: A 21-year-old male presents to the trauma center after
sustaining a gunshot wound to the left upper back resulting in a zone 2 hematoma
and pneumothorax. Bullet fragment artifact interfered with computed tomography.
Carotid angiogram was normal. The patient was discharged after 3 days. He
returned to the Emergency Department 3 months later with a painful pulsatile
hematoma. Computed tomography angiogram revealed a 6-cm pseudoaneurysm arising
from the proximal left internal carotid artery (ICA). A left common carotid
artery (CCA) to ICA bypass with reversed great saphenous vein was performed. The
patient's post-operative course was uneventful, neurologic deficits improved, and
he was discharged. CONCLUSION: Delayed presentation of traumatic pseudoaneurysms
has been reported, although usually these cases are iatrogenic access
complications in extremities. While endovascular therapies are first line for
zone 1 and 3 vascular injuries, management of zone 2 injuries is still
controversial. This patient was treated with a bypass due to the need to evacuate
the hematoma that was exerting a mass effect in the neck.
PMID- 27489720
TI - Use of remote blood releasing system for red cell transfusion in hospice care
center.
AB - OBJECTIVES: It is quite common to have advanced cancer or end-stage renal disease
patients for regular or even frequent blood transfusion in palliative care.
However, due to geographical reason in some hospice centers, blood transfusion is
sometimes difficult if blood bank is closed during non-office hour or not
available. METHODS: Here, we reported a new blood releasing system, that is,
remote blood releasing system, that could be used safely by nursing staff alone
when the blood bank was closed during the night time and holiday. RESULTS: On
call nursing staff could collect red cells successful in these two cases.
CONCLUSION: The new blood releasing system seems useful. However, larger sample
sizes and longer period of study are required to estimate its efficacy and
safety. The provision of antibody-positive red cells and platelet remained a
limitation of this system.
PMID- 27489721
TI - A corny cause of cerebrospinal fluid ascites: A case report and review of
literature.
AB - OBJECTIVE: To report a rare cause of cerebrospinal fluid ascites. METHODS: A 37
year-old female with history of intracranial hypertension and a ventriculo
peritoneal shunt was referred to liver clinic for evaluation of newly developed
ascites. RESULTS: Initially, the cause of ascites was thought to be secondary to
a liver etiology. However, this was excluded after a comprehensive evaluation
including portal pressure measurements. We determined the ascites to be infected
cerebrospinal fluid secondary to a rare commensal organism, Corynebacterium non
Jeikeium, which resolved after removing ventriculo-peritoneal shunt, appropriate
antibiotics and conversion to a ventriculo-atrial shunt. CONCLUSION:
Cerebrospinal fluid ascites is a rare complication of VP shunts and since 1976
only 8 cases of Corynebacterium non jk VP shunt infections have been reported in
the literature but none associated with ascites. Also this report highlights the
beneficial role of transjugular portal pressure measurements in the evaluation of
ascites.
PMID- 27489722
TI - Real-time quantitative PCR assay with Taqman((r)) probe for rapid detection of
MCR-1 plasmid-mediated colistin resistance.
AB - Here we report the development of two rapid real-time quantitative PCR assays
with TaqMan((r)) probes to detect the MCR-1 plasmid-mediated colistin resistance
gene from bacterial isolates and faecal samples from chickens. Specificity and
sensitivity of the assay were 100% on bacterial isolates including 18 colistin
resistant isolates carrying the mcr-1 gene (six Klebsiella pneumoniae and 12
Escherichia coli) with a calibration curve that was linear from 10(1) to 10(8)
DNA copies. Five out of 833 faecal samples from chickens from Algeria were
positive, from which three E. coli strains were isolated and confirmed to harbour
the mcr-1 gene by standard PCR and sequencing.
PMID- 27489723
TI - Dietary beet pulp decreases taurine status in dogs fed low protein diet.
AB - BACKGROUND: It is known that large dogs who are fed lamb and rice diets are at
increased risk to develop taurine-deficiency-induced dilated cardiomyopathy.
Since dogs obligatorily conjugate bile acids (BA) with taurine, we determined
whether rice bran (RB) or other fibers (cellulose; CL, beet pulp; BP) would
affect BA excretion and/or the taurine status of dogs. RESULTS: Eighteen
medium/large mixed-breed dogs were given purified diets containing CL, BP, or RB
for 12 weeks. Taurine concentrations in plasma and whole blood were significantly
decreased at week 12. The BP group, compared to the CL or RB groups, showed
significantly lower taurine concentrations in plasma (6.5 +/- 0.5 vs 20.4 +/- 3.9
and 13.1 +/- 2.0 MUmol/L, respectively, P < 0.01, mean +/- SEM) and in whole
blood (79 +/- 10 vs 143 +/- 14 and 127 +/- 14 MUmol/L, respectively, P < 0.01),
lower apparent protein digestibility (81.9 +/- 0.6 vs 88.8 +/- 0.6 and 88.1 +/-
1.2 %, respectively, P < 0.01), and higher BA excretions (5.6 +/- 0.1 vs 3.4 +/-
0.5 and 3.4 +/- 0.4 MUmol/g feces, respectively, P < 0.05) at week 12.
CONCLUSIONS: These results do not support the hypothesis that RB is likely to be
a primary cause of lamb meal and rice diets, increasing the risk of taurine
deficiency in large dogs. However these indicate that BP may contribute to a
decrease taurine status in dogs by increasing excretion of fecal BA and
decreasing protein digestibility, thus decreasing the bioavailability of sulfur
amino acids, the precursors of taurine.
PMID- 27489724
TI - Study on chemotaxis and chemokinesis of bone marrow-derived mesenchymal stem
cells in hydrogel-based 3D microfluidic devices.
AB - BACKGROUND: Controlling the fate of mesenchymal stems cells (MSCs) including
proliferation, migration and differentiation has recently been studied by many
researchers in the tissue engineering field. Especially, recruitment of stem
cells to injury sites is the first and crucial step in tissue regeneration.
Although significant progress has been made in the chemotactic migration of MSCs,
MSC migration in three dimensional environments remains largely unknown. We
developed a 3D hydrogel-based microfluidic-device to study the migration behavior
of human MSCs in the presence of stromal-cell derived factor-1alpha (SDF-1alpha),
interleukin 8 (IL-8) and Substance P (SP) which have been utilized as
chemoattractant candidates of human mesenchymal stem cells (hMSCs). RESULTS: We
systematically investigated the chemotactic migration behaviors of hMSCs and
their responses to SDF-1alpha, IL-8, and SP. SDF-1alpha was shown to be the most
fascinating chemoattractant candidate among those factors at a certain time
point. We also found that each chemokine showed different chemoattractant
abilities according to their concentration. In the case of SP, this factor showed
chemokinesis not chemotaxis. Especially at a 7-8 * 10(-8) M concentration range,
the chemokinesis ability driven by SP was further increased. The data suggest
that some factors at the optimal concentration exhibit chemokinesis or chemotaxis
in a 3D hydrogel-based microfluidic device. CONCLUSION: In this study on
chemotaxis and chemokinesis of hMSCs, the system parameters such as chemokine
concentration, system stability, and 2D or 3D microenvironment are critically
important to obtain meaningful results.
PMID- 27489725
TI - Direct photo-patterning on anthracene containing polymer for guiding stem cell
adhesion.
AB - BACKGROUND: Various micropatterned surfaces capable of guiding the selective
adhesion of biomolecules such as proteins and cells are of great interests in
biosensor, diagnostics, drug screening, and tissue engineering. In this study, we
described a simple photo-patterning method to prepare micro-patterned films for
stem cell patterning using anthracene containing polymers (PMAn). This micro
patterned polymer film was prepared by the facile photo-reaction of anthracene
units in polymer backbone structure. RESULTS: The UV irradiation of PMAn through
a photomask resulted in the quenching of fluorescent intensity as well as the
changes in surface wettability from hydrophobic to hydrophilic surface. As a
result, UV exposed regions of PMAn film show lower fluorescent intensity as well
as higher proliferation rate of mesenchymal stem cells (MSCs) than unexposed
region of PMAn film. Furthermore, the selective MSC attachment was clearly
observed in the UV exposed regions of PMAn film. CONCLUSION: We developed a
simple cell patterning method with a fluorescent, biocompatible, and patternable
polymer film containing anthracene units. This method provides a facile stem cell
patterning method and could be extended to various patterning of biomaterials
without labor-intensive preparation and no pre-treatment for complex interactions
of cell-microenvironment.
PMID- 27489727
TI - Development of rheumatoid arthritis during treatment of multiple sclerosis with
interferon beta 1-a. Coincidence of two conditions or a complication of
treatment: A case report.
AB - Coexistence of multiple sclerosis (MS) with other autoimmune diseases has been
attributed to common background genetic or environmental factors. This study
presents development of rheumatoid arthritis (RA) during treatment of MS. The MS
was confirmed by the Mc Donald criteria and the diagnosis of RA was confirmed by
the ACR/EULAR criteria. A 35 years old women with 9 years of MS who was receiving
interferon beta 1-a (INF) for 7 years and who did not respond to conventional
therapy of RA over 8 months developed clinical manifestations of RA. But a rapid
response was observed after discontinuation of INF. These findings suggest a
possible contribution of INF in the development of RA.
PMID- 27489726
TI - Flexible selection of diversified Na(+)/K(+)-ATPase alpha-subunit isoforms for
osmoregulation in teleosts.
AB - BACKGROUND AND METHODS: Multiple Na+/K+-ATPase (NKA) alpha-subunit isoforms
express differentially in response to salinity transfer in teleosts but we
observed that the isoform nomenclature is inconsistent with the phylogenetic
relationship of NKA alpha-genes. We cloned the catalytic NKA alpha-subunit
isoforms in eels and medaka, analyzed the time course of their expressions in
osmoregulatory tissues after transfer from freshwater (FW) to seawater (SW), and
performed phylogenetic analyses to deduce an evolutionary scenario that
illustrates how various duplication events have led to the current genomic
arrangement of NKA alpha-genes in teleosts. RESULTS AND DISCUSSION: Five and six
alpha-subunits were cloned in eels and medaka respectively. In eels, the commonly
reported alpha1a and alpha1b isoforms were absent while the alpha1c isoform was
diversified instead (alpha1c-1, alpha1c-2, alpha1c-3, alpha2, and alpha3 in
eels). Phylogenetic estimation indicated that the alpha1a and alpha1b isoforms
from salmon, tilapia, and medaka were generated by independent duplication events
and thus they are paralogous isoforms. Re-examination of expression changes of
known isoforms after salinity challenge revealed that the isoforms selected as
predominant SW-types varied among teleost lineages. Diversification of alpha1
isoforms occurred by various types of gene duplication, or by alternative
transcription among tandem genes to form chimeric transcripts, but there is no
trend for more alpha1 copies in euryhaline species. Our data suggest that the
isoform switching between FW (alpha1a predominates) and SW (alpha1b predominates)
that occurs in salmonids is not universal in teleosts. Instead, in eels, alpha1c
1 was the major alpha-subunit upregulated gill, intestine, and kidney in SW.
Localization of both NKA mRNA and protein showed consistent upregulation in gill
and intestine in SW eels, but not in renal distal and collecting tubules, where
low transcript expression levels were accompanied by high protein levels,
suggesting a tissue-specific translational regulation that determines and fine
tunes the NKA expression. In medaka, alpha1b was upregulated in SW in anterior
intestine while most other alpha-subunit isoforms were less responsive to
salinity changes. CONCLUSION: By integrating gene expression and phylogenetic
results, we propose that the major NKA alpha-subunits for SW acclimation were not
ancestrally selected, but rather were flexibly determined in lineage-specific
fashion in teleosts.
PMID- 27489728
TI - Deeper insight into maternal genetic assessments and demographic history for
Egyptian indigenous chicken populations using mtDNA analysis.
AB - This study principally sought to reveal the demographic expansion of Egyptian
indigenous chickens (EIC) using representative breeds: Sinai (North), Fayoumi
(Middle) and Dandarawi (South) of Egypt as well as to deeply clarify their
genetic diversity, possible matrilineal origin and dispersal routes. A total of
33 partial mitochondrial DNA sequences were generated from EIC and compared with
a worldwide reference dataset of 1290 wild and domestic chicken sequences. Study
populations had 12 polymorphic variable sites and 7 haplotypes. A lack of
maternal substructure between EIC was detected (F ST = 0.003). The unimodal
mismatch distribution and negative values of Tajima's D (-0.659) and Fu's Fs (
0.157) indicated demographic expansion among EIC and pointed to Fayoumi as the
oldest EIC population. Egyptian haplotypes were clustered phylogenetically into
two divergent clades. Their phylogeography revealed an ancient single maternal
lineage of Egyptian chickens likely derived from Indian-Subcontinent. Moreover, a
recent maternal commercial heritage possibly originated in Yunnan-Province and/or
surrounding areas was admixed restrictedly into Sinai. It is implied that Egypt
was an entry point for Indian chicken into Africa and its further dispersal route
to Europe. This study provides a clue supporting the previous assumption that
urged utilizing consistent founder populations having closely related progenitors
for synthetizing a stabilized homogenous crossbreed as a sustainable discipline
in breeding program.
PMID- 27489729
TI - Optimal PMU placement using topology transformation method in power systems.
AB - Optimal phasor measurement units (PMUs) placement involves the process of
minimizing the number of PMUs needed while ensuring the entire power system
completely observable. A power system is identified observable when the voltages
of all buses in the power system are known. This paper proposes selection rules
for topology transformation method that involves a merging process of zero
injection bus with one of its neighbors. The result from the merging process is
influenced by the selection of bus selected to merge with the zero-injection bus.
The proposed method will determine the best candidate bus to merge with zero
injection bus according to the three rules created in order to determine the
minimum number of PMUs required for full observability of the power system. In
addition, this paper also considered the case of power flow measurements. The
problem is formulated as integer linear programming (ILP). The simulation for the
proposed method is tested by using MATLAB for different IEEE bus systems. The
explanation of the proposed method is demonstrated by using IEEE 14-bus system.
The results obtained in this paper proved the effectiveness of the proposed
method since the number of PMUs obtained is comparable with other available
techniques.
PMID- 27489730
TI - Dynamic light scattering of xanthan gum biopolymer in colloidal dispersion.
AB - The dynamical properties of nanogels of xanthan gum (XG) with hydrodynamic radius
controlled in a size range from 5 nm to 35 nm, were studied at the different XG
concentrations in water/sodium bis-2-ethylhexyl-sulfosuccinate (AOT)/decane
reverse micelles (RMs) vs. mass fraction of nano-droplet (MFD) at W = 40, using
dynamic light scattering (DLS). The diffusion study of nanometer-sized droplets
by DLS technique indicated that enhancing concentration of the XG polysaccharide
resulted in exchanging the attractive interaction between nano-gels to repulsive
interaction, as the mass fraction of nano-droplets increased. The reorientation
time (taur ) of water nanodroplets decreased with MFD for water-in-oil AOT micro
emulsion comprising high concentration (0.0000625) of XG. On the other hand,
decreasing concentration of biopolymer led to increasing the rotational
correlation time of water nanodroplets with MFD. In conclusion, a single
relaxation curve was observed for AOT inverse microemulsions containing different
XG concentrations. Furthermore, the interaction between nanogels was changed from
attractive to repulsive versus concentration of XG in the AOT RMs.
PMID- 27489732
TI - Parametric and working fluid analysis of a combined organic Rankine-vapor
compression refrigeration system activated by low-grade thermal energy.
AB - The potential use of many common hydrofluorocarbons and hydrocarbons as well as
new hydrofluoroolefins, i.e. R1234yf and R1234ze(E) working fluids for a combined
organic Rankine cycle and vapor compression refrigeration (ORC-VCR) system
activated by low-grade thermal energy is evaluated. The basic ORC operates
between 80 and 40 degrees C typical for low-grade thermal energy power plants
while the basic VCR cycle operates between 5 and 40 degrees C. The system
performance is characterized by the overall system coefficient of performance
(COPS) and the total mass flow rate of the working fluid for each kW cooling
capacity ([Formula: see text]). The effects of different working parameters such
as the evaporator, condenser, and boiler temperatures on the system performance
are examined. The results illustrate that the maximum COPS values are attained
using the highest boiling candidates with overhanging T-s diagram, i.e. R245fa
and R600, while R600 has the lowest [Formula: see text] under the considered
operating conditions. Among the proposed candidates, R600 is the best candidate
for the ORC-VCR system from the perspectives of environmental issues and system
performance. Nevertheless, its flammability should attract enough attention. The
maximum COPS using R600 is found to reach up to 0.718 at a condenser temperature
of 30 degrees C and the basic values for the remaining parameters.
PMID- 27489731
TI - Temporary amygdala inhibition reduces stress effects in female mice.
AB - The current study investigated the effect of temporary inhibition of amygdala in
response to metabolic changes caused by stress in female mice. Unilateral and
bilateral amygdala cannulation was carried out, and after a week of recovery, 2%
lidocaine hydrochloride was injected into the mice amygdalae five minutes before
the induction of stress. A communication box was employed to induce stress for
four consecutive days and plasma corticosterone, food and water intake, weight
changes, and anorexia were measured as stress-induced metabolic changes. Results
demonstrated that stress, increases stress, increased plasma corticosterone
concentrations, weight, food, and water intake. Temporary inhibition of the
amygdala slightly decreased plasma corticosterone concentrations, but did not
fully reduce the effect of stress. The bilateral injection of lidocaine
hydrochloride to the amygdala reduced the effect of stress and reduced water
intake and weight. Unilateral injection of lidocaine hydrochloride into the left
and right amygdala reduced food intake. In conclusion, the present study
demonstrated that the left side and right side of amygdala nuclei play a
different role in metabolic responses in stress.
PMID- 27489733
TI - Cystoscopy and intravesical bacille Calmette-Guerin therapy in antibiotic-naive
patients with bladder cancer with asymptomatic bacteriuria: An update.
AB - Urologists often insist on sterile urine before invasive outpatient urological
procedures, and urine culture and antibiotics are usually given before cystoscopy
or instillation of bacille Calmette-Guerin (BCG) therapy, especially in patients
who have positive urine cultures. Our experience suggests that cystoscopy and
induction BCG therapy can be performed safely, even in patients with asymptomatic
bacteriuria, without pretreatment or prophylactic antibiotics. The rate of
subsequent febrile urinary tract infection is <4% in both infected and uninfected
patients. Pretreatment antibacterial therapy does not appear to be necessary
before these two outpatient urological procedures in patients with bladder
cancer. Such strategy facilitates timely interventions and reduces the
possibility of antibiotic resistance.
PMID- 27489734
TI - Bulbar urethral stricture: How to optimise the use of buccal mucosal grafts.
AB - The use of buccal mucosa graft urethroplasty (BMGU) for bulbar urethral
strictures has gained widespread popularity since the first report in 1996. Over
the last two decades, there have been many modifications in the surgical
technique. This, along with better understanding of urethral anatomy, has allowed
the BMG to become the 'gold standard' in urethral substitution. The present
article reviews the evolution and techniques of BMGU in order to answer the
question - how do we optimise the use of BMGs?
PMID- 27489735
TI - Phosphodiesterase type 5 inhibitors: Irrational use in Saudi Arabia.
AB - OBJECTIVE: To identify the criteria of phosphodiesterase type 5 inhibitor (PDE5i)
users and to analyse the knowledge, attitude, and practices of PDE5i use amongst
Saudi men. SUBJECTS AND METHODS: A web-based, cross-sectional survey was
conducted in Saudi Arabia between January and April 2015. Sexually active adult
men were interviewed using a website questionnaire designed by the authors.
Descriptive statistics were used to analyse the data. RESULTS: In all, 1008 men
participated in the survey with 378 (37.5%) reporting use of PDE5i. Of those
using PDE5i, 144 (38.1%) reported erectile dysfunction and 234 (61.9%) reported
normal erection (recreational users). We found several demographic features,
including high education level, health field occupation, high income, smoking,
and increased frequency of sexual intercourse amongst the PDE5i users. Most of
the PDE5i users (92.3%) had knowledge about PDE5i and 84.1% of them bought it
without medical prescription. The most commonly used PDE5i was tadalafil (46.1%)
and most of the users (79.9%) reported improvement in their sexual activity after
PDE5i usage. Amongst the recreational users, the main reasons for PDE5i usage
were curiosity (38.5%) and improving self-confidence (25.6%). Of them, 69.2%
reported benefits from PDE5i usage, mainly in the form of enhancement of erection
(36.7%) and increasing erection duration (31.2%). CONCLUSION: PDE5i use appears
to be frequent in Saudi Arabia. Most of the users had knowledge about PDE5i and
claimed to get benefits from it, even if used as a recreational drug.
PMID- 27489736
TI - What is better in percutaneous nephrolithotomy - Prone or supine? A systematic
review.
AB - OBJECTIVE: To review the literature reporting the technique of percutaneous
nephrolithotomy (PCNL) and outcomes for prone and supine PCNL, as PCNL is an
established treatment for renal calculi and both prone and supine PCNL have been
described, but there has been much debate as to the optimal position for renal
access in PCNL. METHODS: A review of the medical literature was conducted using
the PubMed database to identify relevant studies reporting on prone and supine
PCNL published up until July 2015. Only publications in English were considered.
Search terms included 'supine', 'prone', 'percutaneous nephrolithotomy', 'PCNL'
and 'randomised controlled trial'. Articles relevant to the particular aspect of
PCNL discussed were selected. RESULTS: In all, 30 articles were included in the
literature review. Nine of these articles were of Level 1 Evidence as graded by
the Oxford System of Evidence-based Medicine. CONCLUSION: The present systematic
review highlights the benefits and disadvantages of supine and prone PCNL. The
published data on supine and prone PCNL have shown no significant superiority of
either approach. Whether prone or supine PCNL is optimal, remains a debatable
topic.
PMID- 27489737
TI - Does lithotripsy increase stone recurrence? A comparative study between
extracorporeal shockwave lithotripsy and non-fragmenting percutaneous
nephrolithotomy.
AB - OBJECTIVES: To investigate the effect of stone fragmentation on late stone
recurrence by comparing the outcome of extracorporeal shockwave lithotripsy
(ESWL) and non-fragmenting percutaneous nephrolithotomy (PCNL), and to
investigate factors contributing to recurrent calculi. PATIENTS AND METHODS: We
evaluated stone recurrence in 647 patients who initially achieved a stone-free
status after ESWL and compared the outcomes to 137 stone-free patients treated
with PCNL without stone fragmentation. Patients were evaluated every 3 months
during the first year and every 6 months thereafter to censorship or time of
first new stone formation. Stone recurrence rates were calculated using the
Kaplan-Meier method. The effects of demographics, stone characteristics, and
intervention on the recurrence rate were studied using the log-rank test and the
Cox-regression analysis. RESULTS: For ESWL the recurrence rates were 0.8%, 35.8%
and 60.1% after 1, 5 and 10 years, which were comparable to the 1.5%, 35.5% and
74.9%, respectively found in the PCNL group (P = 0.57). Stone burden (>8 mm) and
a previous history of stone disease were significantly associated with higher
recurrence rates regardless of the method of stone intervention (P = 0.02 and P =
0.01, respectively). In the ESWL group, a stone length of >8 mm showed a higher
recurrence rate (P = 0.007). In both the ESWL and PCNL groups, there was a
significant shift from baseline stone location, with an increased tendency for
most new stones to recur in the calyces as opposed to the pelvis. CONCLUSIONS: In
comparison with PCNL, ESWL does not increase long-term stone recurrence in
patients who become stone-free. The stone burden appears to be the primary factor
in predicting stone recurrence after ESWL.
PMID- 27489738
TI - Efficacy and safety of tamsulosin oral-controlled absorption system, solifenacin,
and combined therapy for the management of ureteric stent-related symptoms.
AB - OBJECTIVES: To evaluate the efficacy of solifenacin, tamsulosin oral-controlled
absorption system (OCAS), and the combination of both drugs on JJ stent-related
symptoms using the validated Arabic version of the ureteric stent symptom
questionnaire (USSQ). PATIENTS AND METHODS: In all, 260 patients who had
undergone JJ stenting of the ureter for different endoscopic urological
procedures were postoperatively randomly assigned into four equal groups.
Patients in Group I received no treatment and served as the control group, Group
II patients received tamsulosin OCAS 0.4 mg daily, Group III patients received
solifenacin 5 mg daily, and Group IV patients received a combination of both
drugs. Before stent removal, all patients completed the Arabic version of the
USSQ. RESULTS: In all, 234 patients completed the study, comprised of 56 in Group
I, 59 in Group II, 58 in Group III, and 61 in Group IV. Baseline characteristics
and indications for JJ stenting were comparable in the four groups. There were
highly significant differences in all items of the USSQ between the treatment
groups and the controls, while Group II and III were comparable. The USSQ score
was significantly lower in Group IV vs Groups II and III. Crossing of the distal
curl of the stent to the midline had a significant positive correlation with the
severity of the urinary symptoms, body pain, general health, and work performance
in the medicated groups. CONCLUSIONS: Combined therapy with tamsulosin OCAS 0.4
mg daily and solifenacin 5 mg daily is a safe and well-tolerated management for
stent-related symptoms. However, stent position remains a significant factor
affecting response to medical therapy and patients' health-related quality of
life.
PMID- 27489739
TI - Fluoroscopy free flexible ureteroscopy with holmium: Yttrium-aluminium-garnet
laser lithotripsy for removal of renal calculi.
AB - OBJECTIVE: To evaluate the feasibility of access sheath insertion and ureteric
stent placement without image guidance in flexible ureteroscopic lithotripsy with
holmium:yttrium-aluminium-garnet laser for renal stones. PATIENTS AND METHODS:
Between March 2014 and October 2015, 80 patients with renal stones treated with
flexible ureteroscopic laser lithotripsy were evaluated. Indications for surgery
were renal obstruction, failed shockwave lithotripsy (SWL), stones in polycystic
kidneys, and mal-rotated kidneys. A 6.5-F Cobra flexible ureteroscope was used in
all cases with an access sheath of 12 F, 35/45 cm in length. Fluoroscopy was not
intended for use in all cases and postoperative JJ stenting was optional. The
perioperative complications were listed and the collected data were analysed.
RESULTS: The study included 80 patients (66 male, 14 female), with a mean (SD;
range) age of 48.2 (8; 28-54) years and a stone burden of 13 (3.5; range 6-23)
mm. In all, 26 patients had a stone burden of >15 mm and 48 patients had lower
calyceal stones. The mean (SD; range) operative time was 71.5 (20; 25-130) min.
Overall, 76 (95%) access sheath insertions were performed successfully without
the use of fluoroscopy. JJ stenting was used in 22 patients (27.5%). The mean
(SD; range) hospital stay was 10 (8.5; 10-36) h. After one session, a stone-free
rate (SFR) of 87.5% was achieved (93.3% for stones of <15 mm). A single session
was successful in 87.9% of cases with lower calyceal stones, with a SFR of 91.7%
for post-SWL failure cases. The perioperative complication rate was 15%.
CONCLUSION: Access sheath insertion without fluoroscopic guidance is feasible.
This technique reduces radiation exposure in patients requiring flexible
ureteroscopy.
PMID- 27489740
TI - Single versus multiple instillation of povidone iodine and urographin in the
treatment of chyluria: A prospective randomised study.
AB - OBJECTIVE: To compare the safety, efficacy and complications of single vs
multiple instillations of povidone iodine (PI) and urographin as a sclerosing
agent in the treatment of chyluria. PATIENTS AND METHODS: The study included 58
patients diagnosed with chyluria between March 2006 and January 2013. The
inclusion criteria were either severe attacks of chyluria or patients with mild
to-moderate chyluria who had failed conservative treatment. The patients were
randomly allocated to one of two groups: those in Group A had a single
instillation of a combination of PI 0.2% plus the contrast-agent urographin 76%,
while those in Group B had multiple instillations of the same combination twice
daily for 3 successive days. RESULTS: The mean (SD) age of the patients in Groups
A and B was 38.22 (10.67) and 37.9 (10.86) years, respectively. Chyluria was
severe in eight patients (14.8%), moderate in 25 (46.3%) and mild in 21 (38.9%).
The success rate in Group A (single instillation) was 85.2% and in Group B
(multiple instillation) was 88.9%. The recurrence rate in Group A was 14.8% with
a disease-free duration (DFD) of 4-15 weeks, while in group B it was 11.1% with a
DFD of 6-18 weeks. CONCLUSION: There was no significant difference between a
single instillation of a combination of PI 0.2% and urographin 76% as a
sclerosing agent in the treatment of chyluria and multiple instillations.
However, the single instillation protocol is more cost effective with a shorter
hospital stay.
PMID- 27489741
TI - Feasibility and safety of laparoscopic adrenalectomy for large tumours.
AB - OBJECTIVE: To verify the feasibility and safety of laparoscopic adrenalectomy for
large tumours, as since it was described, the laparoscopic approach for
adrenalectomy has become the 'gold standard' for small tumours and for large and
non-malignant adrenal tumours many studies have reported acceptable results.
PATIENTS AND METHODS: This is a retrospective study from a general surgery
department from January 2006 to December 2013 including 45 patients (56
laparoscopic adrenalectomies). We divided patients into two groups according to
tumour size: <5 or ?5 cm, we compared demographic data and peri- and
postoperative outcomes. RESULTS: There was no statistical difference between the
two groups for conversion rate (3.7% vs 11.7% P = 0.32), postoperative
complications (14% vs 12%, P = 0.4), postoperative length of hospital stay (5 vs
6 days P = 0.43) or mortality (3.5% vs 0% P = 0.99). The only statistical
difference was the operating time, at a mean (SD) 155 (60) vs 247 (71) min (P <
0.001). CONCLUSION: Laparoscopic adrenalectomy for large tumours needs more time
but appears to be safe and feasible when performed by experienced surgeons.
PMID- 27489743
TI - Prostate tissue retrieval after holmium laser enucleation of the prostate;
assessment of non-morcellation approaches.
PMID- 27489742
TI - Prostate tissue retrieval after holmium laser enucleation of the prostate;
assessment of non-morcellation approaches.
AB - OBJECTIVES: To review non-morcellation approaches for tissue retrieval after
holmium laser enucleation of the prostate (HoLEP) and whether these approaches
demolish the advantages of the HoLEP procedure. PATIENTS AND METHODS: We reviewed
our prospectively maintained laser prostate database for HoLEP procedures where
non-morcellation approaches were used for retrieval of the enucleated adenoma.
Non-morcellation approaches were adopted in cases of morcellator malfunction or
whenever concomitant pathology indicated laparotomy. Patients were stratified
into the laparotomy group (Group I) or the transurethral resection (TUR) group
(Group II). Safety and efficacy of each approach were assessed and compared.
RESULTS: Between August 2012 and July 2015, of 392 HoLEP procedures non
morcellation approaches were used for tissue retrieval in 37 (9.4%). In 19
procedures a laparotomy approach was adopted (17 mini-laparotomies and two
conventional laparotomies for concomitant diverticulectomy). TUR of the
enucleated adenoma was adopted in 18 patients. Baseline demographic data and
indications for surgery were comparable between the groups. However,
significantly larger prostates were treated in Group I. There were no significant
differences between the groups for tissue retrieval time, histopathological
findings of retrieved tissue, and peri-procedure biochemical changes. However,
significantly more tissue was retrieved (median tissue weight 115 vs 38 g) and at
a faster rate (4.6 vs 1.09 g/min) in Group I. The median hospital stay was
similar in both groups, but the median time to catheter removal was longer in
Group I (5 vs 2 days). Minimal and similar peri-procedure complications were
reported in both groups and in both groups there was a significant and comparable
improvement in all urinary outcome measures. CONCLUSION: In the absence or
malfunction of a tissue morcellator, or whenever concomitant pathology indicates
laparotomy, non-morcellation tissue retrieval approaches are feasible options for
endourologists practicing transurethral enucleation of prostate adenoma. These
approaches are valid alternatives retaining most of the advantages of the
transurethral prostate enucleation procedure.
PMID- 27489744
TI - Benign prostatic hyperplasia, metabolic syndrome and androgenic alopecia: Is
there a possible relationship?
AB - OBJECTIVE: To evaluate the incidence of benign prostatic hyperplasia (BPH) and
metabolic syndrome in patients with androgenetic alopecia (AGA) in comparison
with those with no AGA, as several previous studies have reported inconsistent
results of an association between metabolic syndrome and BPH with AGA. PATIENTS
SUBJECTS AND METHODS: This cross-sectional study included 400 participants,
divided into 300 patients diagnosed with AGA, with different grades according to
Norwood-Hamilton classification, and 100 control subjects with no AGA. Criteria
for diagnosis of metabolic syndrome according to Adult Treatment Panel-III
criteria (waist circumference, blood pressure, fasting blood sugar, high-density
lipoprotein and triglycerides), as well as criteria for diagnosis of BPH
(prostatic volume, urine flow, and prostate-specific antigen) were assessed in
all patients and compared with the control subjects. RESULTS: There were
significant differences between the AGA and no-AGA groups for the following
variables: waist circumference, body mass index, fibrinogen level, fasting blood
sugar, cholesterol, C-reactive protein, erythrocyte sedimentation rate, and
glycosylated haemoglobin. There was a significant difference in number of
patients with AGA manifesting criteria of metabolic syndrome (51% vs 28%), as
well as BPH diagnostic criteria (36% vs 6.8%) compared with the control subjects.
Both BPH and metabolic syndrome were shown to be significant independent
variables associated with AGA. CONCLUSIONS: Dermatologists, urologists, and
primary care physicians should monitor patients with early onset AGA for the
development of urinary symptoms, to permit an earlier diagnosis of BPH; and for
metabolic syndrome symptoms, to permit early diagnosis of cardiovascular risk
factors.
PMID- 27489745
TI - Tubularised incised-plate versus tubularisation of an intact and laterally
augmented plate for hypospadias repair: A prospective randomised study.
AB - OBJECTIVES: To compare the outcome of hypospadias repair using tubularised
incised-plate (TIP) urethroplasty and tubularisation of an intact and laterally
augmented urethral plate. PATIENTS AND METHODS: This prospective randomised study
included 370 patients with primary distal hypospadias. All had urethral plate
widths of 8-10 mm and a glans of ?15 mm. Exclusion criteria were previous repair,
circumcision, a wide urethral plate of >10 mm or a narrow plate of <8 mm in
diameter, a small glans of <15 mm in diameter, chordee of >30 degrees , and
hormonal stimulation. Patients were randomised into two groups: Group 1 (185
patients) underwent TIP urethroplasty and Group 2 (185 patients) underwent
tubularisation of the intact plate with lateral augmentation of the urethral
plate using penile skin. The follow-up period was 12-28 months. RESULTS: There
were 172 evaluable patients in Group 1 and 177 in Group 2. The urethroplasty was
successful in 83.2% and 94.4% in Groups 1 and 2, respectively. Complications
occurred in 16.8% in Group 1 and 5.6% in Group 2 (P = 0.001). Meatal stenosis
occurred in 7% and 3.4% in Groups 1 and 2, respectively (P = 0.130). There were
statistically significant differences in the wound dehiscence, fistula, and re
operation rates of Group 1 versus Group 2, at 6% versus 0%, 9.8% versus 2.8%, and
13.4% versus 5.6%, respectively. The presence of mild chordee did not affect the
complication rate (P = 0.242). The mean (SD) operative time was 56.7 (8.9) min in
Group 1 and 93.7 (8.3) min in Group 2 (P < 0.001). CONCLUSION: The outcome of
tubularised intact and laterally augmented plate is better than classical TIP
urethroplasty of hypospadias. Further trials are mandatory to extend the
indications of the technique.
PMID- 27489746
TI - Parameter Estimation Using Divide-and-Conquer Methods for Differential Equation
Models.
PMID- 27489747
TI - Towards Self-regenerating Antimicrobial Polymer Surfaces.
AB - Regeneration of functional polymer surfaces after damage or contamination is an
unresolved scientific challenge, and also of practical importance. In this proof
of-concept study, we present a method to regenerate a functional surface property
using a polymer multi-layer architecture. This is exemplified using
antimicrobially active surfaces. The idea is to shed the top layer of the polymer
layer stack, like a reptile shedding its skin. The proof-of-concept stack
consists of two antimicrobial layers and a degradable interlayer. Shedding of the
top layer is enabled by degrading that interlayer. The shedding process was
analyzed by quantitative fluorescence microscopy, ellipsometry, and FTIR
spectroscopy. Antimicrobial assays revealed that the functionality of the
emerging antimicrobial layer was fully retained after shedding.
PMID- 27489748
TI - Novel Transabdominal Motor Action Potential (TaMAP) Neuromonitoring System for
Spinal Surgery.
AB - INTRODUCTION: Minimally invasive lateral lumbar interbody fusion (LLIF)
approaches to the lumbar spine reduce patient morbidity compared to anterior or
posterior alternatives. This approach, however, decreases direct anatomical
visualization, creating the need for highly sensitive and specific
neurophysiological monitoring. We seek to determine feasibility in
'transabdominal motor action potential (TaMAP)' monitoring as an assessment for
the integrity of the neural elements during lateral-approach surgeries to the
lumbar spine. METHODS: Cathode and anode leads were placed on the posterior and
anterior surfaces of two porcine subjects. Currents of varying degrees were
transmitted across, from front to back. Motor responses were monitored and
recorded by needle electrodes in specific distal muscle groups of the lower
extremity. Lastly, the cathode and anode were placed anterior and posterior to
the chest wall and stimulated to the maximum of 1500 mA to determine any effect
on cardiac rhythm. RESULTS: Responses were seen by measuring vertical height
differences between peaks of corresponding evoked potentials. Recruitment began
at 200 mA in the lower extremities. Stimulation at 450 mA recruited a reliable
and distinguishable electrographic response from most muscle groups. Responses
were recorded and reliably measured and increased in proportion to the graduation
of transabdominal stimulation current; no responses were seen in the arms or
face. 1500 mA across the chest wall failed to stimulate or induce cardiac
arrhythmia on repeated stimulation, indicating safety of stimulation. CONCLUSION:
TaMAPs seen in the animal model provide a potential alternative to standard
transcranial motor evoked potentials done in the lateral approach of LLIFs. TaMAP
recordings in most muscle groups were recordable and reliable, though some muscle
groups failed to stimulate. Safety of transabdominal motor evoked potentials was
confirmed in this porcine study. Future studies should examine TaMAPs reliability
in detecting compressive lesions of nerve roots and peripheral nerves.
PMID- 27489749
TI - Implementing an Innovative Prehospital Care Provider Training Course in Nine
Cambodian Provinces.
AB - Despite significant improvements in health outcomes nationally, many Cambodians
continue to experience morbidity and mortality due to inadequate access to
quality emergency medical services. Over recent decades, the Cambodian healthcare
system and civil infrastructure have advanced markedly and now possess many of
the components required to establish a well functioning emergency medical system.
These components include enhanced access to emergency transportation through
large scale road development efforts, widspread availability of emergency
communication channels via the spread of cellphone and internet technology, and
increased access to health services for poor patients through the implementation
of health financing schemes. However, the system still lacks a number of key
elements, one of which is trained prehospital care providers. Working in
partnership with local providers, our team created an innovative, Cambodia
specific prehospital care provider training course to help fill this gap.
Participants received training on prehospital care skills and knowledge most
applicable to the Cambodian healthcare system, which was divided into four
modules: Basic Prehospital Care Skills and Adult Medical Emergencies, Traumatic
Emergencies, Obstetric Emergencies, and Neonatal/Pediatric Emergencies. The
course was implemented in nine of Cambodia's most populous provinces, concurrent
with a number of overarching emergency medical service system improvement
efforts. Overall, the course was administered to 1,083 Cambodian providers during
a 27-month period, with 947 attending the entire course and passing the course
completion exam.
PMID- 27489750
TI - Conservative Treatment for Bilateral Displaced Proximal Humerus Head Fracture.
AB - Proximal humerus fracture represents five to eight percent of all fractures and
is twice as common in women than in men. Most cases of displaced fracture of the
proximal humerus are treated surgically; it is probable that more cases are
preferred to be treated surgically greater than required. The optimal treatment
for these fractures remains controversial, but physicians have a tendency to
treat via open reduction and fixation with angular locking plates or glenohumeral
arthroplasty. We present a case of a 71-year-old woman with bilateral displaced
proximal humeral fracture. Conservative treatment was initiated with two hanging
casts, achieving radiological reduction on week one. After two additional weeks
of casting, treatment continued with radiologic control and home physical
therapy, ultimately an excellent functional outcome and adequate radiological
reduction was obtained. Even in bilaterally displaced proximal humerus
fractures, conservative treatment can be an efficient option, reducing
complications, reaching adequate functional results and acceptable radiographic
reduction..
PMID- 27489751
TI - Treatment of Aggressive Prolactin-Secreting Pituitary Adenomas with Adjuvant
Temozolomide Chemotherapy: A Review.
AB - Most prolactin-secreting pituitary adenomas demonstrate slow growth and are
effectively managed with medical/surgical therapy. Rarely, these tumors can
behave aggressively with rapid growth and invasion of local tissues, and are
refractory to medical, surgical, or radio-surgical therapies. We report a case of
a prolactin-secreting adenoma in a young woman, which became progressively
aggressive and refractory to usual treatment modalities, but responded to
treatment with the chemotherapeutic agent temozolomide. In addition, we review
the literature for treatment of refractory adenomas with temozolomide. The
clinical and pathologic characteristics of aggressive prolactin-secreting
adenomas are reviewed, as well as their response to dopamine agonists, surgery,
radiotherapy, and chemotherapy.
PMID- 27489752
TI - NPH Log: Validation of a New Assessment Tool Leading to Earlier Diagnosis of
Normal Pressure Hydrocephalus.
AB - INTRODUCTION: Early treatment of normal pressure hydrocephalus (NPH) yields
better postoperative outcomes. Our current tests often fail to detect significant
changes at early stages. We developed a new scoring system (LP log score) to
determine if this tool is more sensitive in detecting clinical differences than
current tests. MATERIAL AND METHODS: Sixty-two consecutive new patients with
suspected idiopathic NPH were studied. Secondary, previously treated and
obstructive cases were not included. We collected age, pre- and post-lumbar
puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log
scores. The LP log score is recorded at baseline and for seven consecutive days
after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the
diagnostic accuracy of the tests for surgical indication. RESULTS: The post-LP
log showed improvement in 90% of people with good baseline gait tests and in 93%
of people who did not show any pre-LP and post-LP change in gait tests.
Sensitivity, specificity, and accuracy to detect intention to treat when positive
post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and
34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%,
respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%,
respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and
post-LP Tinetti improvement were not associated with a surgical indication (p >
0.05). LP log improvement was associated with surgical indication odds ratio
(OR): 24.5 95% CI (2.4-248.12) (p = 0.007). CONCLUSIONS: LP log showed better
sensitivity, diagnostic accuracy, and association with surgical indication than
the current diagnostic approach. An LP log may be useful detecting NPH patients
at earlier stages and, therefore, yield better surgical outcomes.
PMID- 27489753
TI - Perforation of the Colon During Imatinib Mesylate (Gleevec) Treatment in a
Patient with Chronic Myeloid Leukemia (CML).
AB - Imatinib (Gleevec; STI-571) is a tyrosine-kinase inhibitor (TKI) used in the
treatment of multiple cancers, most notably Philadelphia chromosome-positive
(Ph+) chronic myelogenous leukemia (CML) as well as gastrointestinal stromal
tumor (GIST). The most common adverse effects with imatinib include superficial
edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, and
gastrointestinal side effects. Less frequent side effects include pancytopenia,
febrile neutropenia, flushing, and liver function test abnormalities. Very rare
side effects include secondary malignancies, Sweet's syndrome, angioedema, or
cardiac arrest. We report the first case report of gastrointestinal perforation
complicating imatinib treatment for CML. Unlike other antiangiogenic TKIs such as
sunitinib or sorafenib that target vascular endothelial growth factor (VEGF) and
known to cause gastrointestinal perforation, imatininib is a TKI with no known
anti-VEGF activity, and so it remains unclear how imatinib would be associated
with developing this life threatening complication. However, physicians caring
for patients of imatinib should be aware of this potential toxicity. We suggest
that careful attention and an appropriate clinical evaluation are required for
patients presenting with gastrointestinal symptoms during imatinib treatment.
PMID- 27489755
TI - Arthroscopic Bullet Removal From the Central and Peripheral Compartments of the
Hip Joint.
AB - Recent advances in hip arthroscopy offer an approach for treating an uncommon but
highly disabling injury from intra-articular missile injury to the hip. Hip
arthroscopy affords the patient the benefit of minimally invasive surgery while
allowing for the diagnosis and treatment of concomitant pathology, which may be
either acute, from the trauma of the missile, or chronic. We present a technique
for the removal of projectiles from the central and peripheral compartments of
the hip joint. Through a surgical series of a variety of gunshot wounds, we
detail the unique aspects of retrieval for the various missile endpoints. We
describe this technique for bullets or pieces of bullets lodged within the hip
joint space, bone of the acetabulum, or femoral head. Furthermore, we provide an
example in which hip arthroscopy is not a suitable option for treatment because
of the resulting fracture pattern, which necessitates open reduction along with
internal fixation.
PMID- 27489756
TI - Basic Hip Arthroscopy: Anatomic Establishment of Arthroscopic Portals Without
Fluoroscopic Guidance.
AB - Hip arthroscopy has gained popularity in recent years for diagnostic and
therapeutic hip preservation management. This article details the establishment
of arthroscopic portals of the hip, specifically the anterolateral and modified
anterior portals without fluoroscopic guidance. The anterolateral portal is
established anatomically, and the modified anterior portal is then established
under arthroscopic guidance. A through understanding of the hip anatomy allows
for these portals to be made both safely and reliably for hip arthroscopies in
the modified supine positioned patient. The reduced use of fluoroscopy with this
technique lowers the risk of ionizing radiation exposure to the patient and
surgeon.
PMID- 27489754
TI - Non-Pharmacological Treatments for ADHD in Youth.
AB - BACKGROUND: Complementary and alternative medicine (CAM) in psychiatry or
integrative psychiatry covers a wide range of biological, psychological and mind
body treatments that enhance standard medical practices and patient outcomes.
While CAM approaches are popular amongst patients in their practice as well as in
self-report because of their ease of use, health professionals have received
limited education in these interventions and often are unaware of their patients'
use of CAM treatments. METHOD: This overview highlights evidence-based CAM
treatments for attention deficit hyperactivity disorder (ADHD) including dietary
interventions, phytomedicines, mind-body practices and neurofeedback. RESULTS:
While conventional treatments are the mainstays for ADHD, there are a large
number of available treatments that can be used to enhance treatment response.
CONCLUSION: With improved education and further scientific and clinical research,
validated integrative treatments will provide more effective, lower risk and
lower cost care for patients with ADHD.
PMID- 27489757
TI - Superficial Medial Collateral Ligament of the Knee: Anatomic Augmentation With
Semitendinosus and Gracilis Tendon Autografts.
AB - The superficial medial collateral ligament (sMCL) and associated knee structures
are the most commonly injured structures of the knee. Most isolated sMCL tears
are treated nonoperatively. Several studies have described different algorithms
for treatment of sMCL lesions, as well as different types of techniques, both in
the acute and in chronic settings. The purpose of this article was to detail our
anatomic sMCL augmentation technique using semitendinosus and gracilis tendon
autografts.
PMID- 27489758
TI - Recurrent hydropneumothorax: An unusual presentation for malignant pleural
mesothelioma.
AB - Mesothelioma is a rare pulmonary malignancy commonly associated with asbestos
exposure. Its presentation is insidious and non-specific, with complaints of
chest pain, dyspnea and cough. Chest X-ray may demonstrate unilateral pleural
effusion. CT and PET scans may highlight nodular pleural plaques. Diagnosis often
times is difficult with negative imaging and negative pleural fluid studies. In
rare cases, hydropneumothoraces may be seen. We report a case of malignant
pleural mesothelioma presenting as recurrent hydropneumothorax with negative CT
scan of the chest for pleural abnormalities and negative pleural fluid studies.
PMID- 27489759
TI - Fractured metallic tracheostomy tube: A rare complication of tracheostomy.
AB - Although tracheostomy is a well-accepted procedure for airway management, some
early and late complications may occur. Fracture of the tracheostomy tube (TT) is
a rare complication, particularly in a patient with long-term use. Herein we
report a case of fractured metallic TT migrating into the tracheobronchial tree.
Rigid bronchoscopy was performed through the tracheostomy stoma and the fractured
tube was successfully removed by a balloon catheter. Appropriate cleaning,
routine careful examination, and scheduled replacement of the TT may help prevent
this complication.
PMID- 27489760
TI - A case of pulmonary Mycobacterium avium infection in an immunocompetent patient
who showed a huge consolidation with a high FDG uptake on PET/CT.
AB - We encountered a middle-aged afebrile immunocompetent woman with a slight cough.
Positron emission tomography (PET)/computed tomography (CT) revealed a broad left
upper-lobe consolidation without cavity lesions, small nodules, or bronchiectasis
showing a positive fluorodeoxyglucose (FDG) uptake with a maximum standardized
uptake value (SUVmax) of 26.9. Percutaneous needle lung biopsy specimens showed
caseous granulomas without atypical cells and Mycobacterium avium was cultured
from left pleural effusion, which developed after the biopsy. The consolidation
significantly decreased following combination chemotherapy for approximately 2
years. Clinicians should remember that pulmonary M. avium infection could result
in a large consolidation without other typical radiological findings.
PMID- 27489761
TI - About the effect of pulmonary rehabilitation on lung function in patients with
chronic obstructive pulmonary disease.
AB - Detecting an improvement of lung function in a patient with chronic obstructive
pulmonary disease (COPD) following pulmonary rehabilitation (PR) may appear
unexpected, but actually recent studies showed that is not so rare. In fact, in a
prospective study comparing a group of 190 COPD patients undergoing PR to a group
of 67 patients treated only with drugs a mean improvement of FEV1 from 1240 mL to
1252.4 mL was found in the former, while the values changed from 1367 mL to 1150
mL in the latter (p < 0.001). Such improvement was detected also in a study in
patients with very severe COPD, as assessed by a FEV1 increasing from 970 mL at
baseline to 1080 mL after a 3-week PR inpatient program (p < 0.001). These
observations suggest that improvement of lung function in COPD patients
undergoing PR should be included among the expected outcomes and routinely
assessed as an index of clinical success during the treatment.
PMID- 27489762
TI - A favorable clinical effect of an expectorant in allergic bronchopulmonary
mycosis caused by Schizophyllum commune.
AB - An 80-year-old Japanese woman with wet cough and dyspnea was diagnosed with
pneumonia at a clinic. Antibiotics did not improve her symptoms; therefore, she
was referred to our hospital one month after symptom onset. Chest radiograph
findings revealed complete collapse of the left lung. Bronchoscopy showed white
mucus plug in the left main bronchus, which could not be removed. She was
initially treated with bromhexine. Subsequently, culture results of the mucus
plug specimen obtained during bronchoscopy yielded Schizophyllum commune. After
three weeks, improvement of the collapsed lung was observed on chest radiograph.
PMID- 27489763
TI - Nodular glomerulosclerosis in a patient with cystic fibrosis, but not diabetes
mellitus: A paediatric case.
AB - BACKGROUND: Nodular glomerulosclerosis is seen in insulin dependent diabetic
patients with nephropathy. Kimmelstiel-Wilson nodules on biopsy are considered
pathognomonic. Diabetic nephropathy is a spectrum of glomerular and tubular
disease which correlates with the duration of the diabetes and the extent of
glycaemic control. CASE REPORT: An eleven year old girl with cystic fibrosis was
referred with persistent heavy proteinuria. She underwent a renal biopsy which
revealed nodular glomerulosclerosis with Kimmelstiel-Wilson-like nodules. Her
investigations for diabetes were negative and she was treated with enalapril.
CONCLUSION: Nodular glomerulosclerosis in the absence of diabetes and poor
glycaemic control have not previously been reported in a paediatric patient. In
adult patients without diabetes, smoking, hypertension, hypercholestrolaemia and
extrarenal vascular disease have been implicated. The proteinuria decreased after
commencement of treatment with enalapril. A recurrence of proteinuria responded
to a dose increase.
PMID- 27489764
TI - Changing of IKZF1 genotype during Philadelphia-negative precursor-B acute
lymphoblastic leukemia progression: a short clinical report.
AB - *The case demonstrated a rare event of clonal heterogeneity by IKZF1 gene status
in BCRABL1- ALL.*IKZF1 deletions are secondary events in ALL caused by clonal
evolution during the treatment.*It's prognostic significance could be more
crucial in BCR-ABL- rather than in BCR-ABL + ALL.*IKZF1 gene alterations may be
determined and proved at the genome, expression and protein level.*IKZF1
deletions are suitable for MRD detection but not stable compared to Ig/TCR
rearrangement.
PMID- 27489765
TI - A remarkable hematological and molecular response pattern in a patient with
polycythemia vera during combination therapy with simvastatin and alendronate.
AB - We report a 57-year old man with polycythemia vera, who had a remarkable
hematological and molecular response during treatment with simvastatin and
alendronate. The patient was treated with this combination for 56 months, and
during this period the patient has been in complete hematological remission. The
JAK2-V617F allele burden has dropped from 64% to sustained values below 20%, and
follow-up bone marrow biopsies have revealed no change in PV features, without
any regular cytoreductive treatment.
PMID- 27489766
TI - Enhanced international prognostic index in Japanese patients with diffuse large B
cell lymphoma.
AB - To evaluate the National Comprehensive Cancer Network (NCCN) International
Prognostic Index (IPI), we analyzed 284 patients treated with the combination of
rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in
our institution in Japan. Their 5-year overall survival (OS) by risk level was
80.7%, 74.8%, 55.4% and 67.5% (P=0.005); and their 5-year progression-free
survival (PFS) was 76.8%, 78.6%, 63.7% and 58.3% (P=0.0722). The NCCN-IPI is a
simple scale that uses conventional clinical factors, but did not reflect
survival in our cohort. The NCCN-IPI may require further evaluation for different
regions and ethnicities before adopting it for routine clinical use.
PMID- 27489768
TI - Giant early components of somatosensory evoked potentials to tibial nerve
stimulation in cortical myoclonus.
AB - Enlarged cortical components of somatosensory evoked potentials (giant SEPs)
recorded by electroencephalography (EEG) and abnormal somatosensory evoked
magnetic fields (SEFs) recorded by magnetoencephalography (MEG) are observed in
the majority of patients with cortical myoclonus (CM). Studies on simultaneous
recordings of SEPs and SEFs showed that generator mechanism of giant SEPs
involves both primary sensory and motor cortices. However the generator sources
of giant SEPs have not been fully understood as only one report describes clearly
giant SEPs following lower limb stimulation. In our study we performed a combined
EEG-MEG recording on responses elicited by electric median and tibial nerve
stimulation in a patient who developed consequently to methyl bromide
intoxication CM with giant SEPs to median and tibial nerve stimuli. SEPs wave
shapes were identified on the basis of polarity-latency components (e.g. P15-N20
P25) as defined by earlier studies and guidelines. At EEG recording, the SEP
giant component did not appear in the latency range of the first cortical
component for median nerve SEP (N20), but appeared instead in the range of the
P37 tibial nerve SEP, which is currently identified as the first cortical
component elicited by tibial nerve stimuli. Our MEG and EEG SEPs recordings also
showed that components in the latency range of P37 were preceded by other
cortical components. These findings suggest that lower limb P37 does not
correspond to upper limb N20. MEG results confirmed that giant SEFs are the
second component from both tibial (N43m-P43m) and median (N27m-P27m) nerve
stimulation. MEG dipolar sources of these giant components were located in the
primary sensory and motor area.
PMID- 27489767
TI - Automated subfield volumetric analysis of hippocampus in temporal lobe epilepsy
using high-resolution T2-weighed MR imaging.
AB - BACKGROUND AND PURPOSE: Automated subfield volumetry of hippocampus is desirable
for use in temporal lobe epilepsy (TLE), but its utility has not been
established. Automatic segmentation of hippocampal subfields (ASHS) and the new
version of FreeSurfer software (ver.6.0) using high-resolution T2-weighted MR
imaging are candidates for this volumetry. The aim of this study was to evaluate
hippocampal subfields in TLE patients using ASHS as well as the old and new
versions of FreeSurfer. MATERIALS AND METHODS: We recruited 50 consecutive
unilateral TLE patients including 25 with hippocampal sclerosis (TLE-HS) and 25
without obvious etiology (TLE-nonHS). All patients and 45 healthy controls
underwent high-resolution T2-weighted and 3D-volume T1-weighted MRI scanning. We
analyzed all of their MR images by FreeSurfer ver.5.3, ver.6.0 and ASHS. For each
subfield, normalized z-scores were calculated and compared among groups. RESULTS:
In TLE-HS groups, ASHS and FreeSurfer ver.6.0 revealed maximal z-scores in
ipsilateral cornu ammonis (CA) 1, CA4 and dentate gyrus (DG), whereas in
FreeSurfer ver.5.3 ipsilateral subiculum showed maximal z-scores. In TLE-nonHS
group, there was no significant volume reduction by either ASHS or FreeSurfer.
CONCLUSIONS: ASHS and the new version of FreeSurfer may have an advantage in
compatibility with existing histopathological knowledge in TLE patients with HS
compared to the old version of FreeSurfer (ver.5.3), although further
investigations with pathological findings and/or surgical outcomes are desirable.
PMID- 27489769
TI - Diffusivity in multiple sclerosis lesions: At the cutting edge?
AB - BACKGROUND: Radial Diffusivity (RD) has been suggested as a promising biomarker
associated with the level of myelination in MS lesions. However, the level of RD
within the lesion is affected not only by loss of myelin sheaths, but also by the
degree of tissue destruction. This may lead to exaggeration of diffusivity
measures, potentially masking the effect of remyelination. OBJECTIVE: To test the
hypothesis that the T2 hyperintense lesion edge that extends beyond the T1
hypointense lesion core is less affected by tissue loss, and therefore a more
appropriate target for imaging biomarker development targeting de- and re
myelination. METHOD: Pre- and post-gadolinium (Gd) enhanced T1, T2 and DTI images
were acquired from 75 consecutive RRMS patients. The optic radiation (OR) was
identified in individual patients using a template-based method. T2 lesions were
segmented into T1-hypointense and T1-isointense areas and lesion masks
intersected with the OR. Average Radial, Axial and Mean diffusivity (RD, AD and
MD) and fractional anisotropy (FA) were calculated for lesions of the entire
brain and the OR. In addition, Gd enhancing lesions were excluded from the
analysis. RESULTS: 86% of chronic T2 lesions demonstrated hypointense areas on T1
weighted images, which typically occupied the central part of each T2 lesion,
taking about 40% of lesional volume. The T1-isointense component of the T2 lesion
was most commonly seen as a peripheral ring of relatively constant thickness ("T2
rim"). While changes of diffusivity between adjacent normal appearing white
matter and the "T2-rim" demonstrated a disproportionally high elevation of RD
compare to AD, the increase of water diffusion was largely isointense between the
"T2-rim" and T1-hypointense parts of the lesion. CONCLUSION: Distinct patterns of
diffusivity within the central and peripheral components of MS lesions suggest
that axonal loss dominates in the T1 hypointense core. The effects of
de/remyelination may be more readily detected in the "T2-rim", where there is
relative preservation of structural integrity. Identifying and separating those
patterns has an important implication for clinical trials of both neuroprotective
and, in particular, remyelinating agents.
PMID- 27489770
TI - Quantifying patterns of brain activity: Distinguishing unaffected siblings from
participants with ADHD and healthy individuals.
AB - Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent and
heritable psychiatric disorders. While previous studies have focussed on mapping
focal or connectivity differences at the group level, the present study employed
pattern recognition to quantify group separation between unaffected siblings,
participants with ADHD, and healthy controls on the basis of spatially
distributed brain activations. This was achieved using an fMRI-adapted version of
the Stop-Signal Task in a sample of 103 unaffected siblings, 184 participants
with ADHD, and 128 healthy controls. We used activation maps derived from three
task regressors as features in our analyses employing a Gaussian process
classifier. We showed that unaffected siblings could be distinguished from
participants with ADHD (area under the receiver operating characteristic curve
(AUC) = 0.65, p = 0.002, 95% Modified Wald CI: 0.59-0.71 AUC) and healthy
controls (AUC = 0.59, p = 0.030, 95% Modified Wald CI: 0.52-0.66 AUC), although
the latter did not survive correction for multiple comparisons. Further,
participants with ADHD could be distinguished from healthy controls (AUC = 0.64,
p = 0.001, 95% Modified Wald CI: 0.58-0.70 AUC). Altogether the present results
characterise a pattern of frontolateral, superior temporal and inferior parietal
expansion that is associated with risk for ADHD. Unaffected siblings show
differences primarily in frontolateral regions. This provides evidence for a
neural profile shared between participants with ADHD and their healthy siblings.
PMID- 27489771
TI - Discriminating among degenerative parkinsonisms using advanced (123)I-ioflupane
SPECT analyses.
AB - (123)I-ioflupane single photon emission computed tomography (SPECT) is a
sensitive and well established imaging tool in Parkinson's disease (PD) and
atypical parkinsonian syndromes (APS), yet a discrimination between PD and APS
has been considered inconsistent at least based on visual inspection or simple
region of interest analyses. We here reappraise this issue by applying advanced
image analysis techniques to separate PD from the various APS. This study
included 392 consecutive patients with degenerative parkinsonism undergoing
(123)I-ioflupane SPECT at our institution over the last decade: 306 PD, 24
multiple system atrophy (MSA), 32 progressive supranuclear palsy (PSP) and 30
corticobasal degeneration (CBD) patients. Data analysis included voxel-wise
univariate statistical parametric mapping and multivariate pattern recognition
using linear discriminant classifiers. MSA and PSP showed less ioflupane uptake
in the head of caudate nucleus relative to PD and CBD, yet there was no
difference between MSA and PSP. CBD had higher uptake in both putamen relative to
PD, MSA and PSP. Classification was significant for PD versus APS (AUC 0.69, p <
0.05) and between APS subtypes (MSA vs CBD AUC 0.80, p < 0.05; MSA vs PSP AUC
0.69 p < 0.05; CBD vs PSP AUC 0.69 p < 0.05). Both striatal and extra-striatal
regions contain classification information, yet the combination of both regions
does not significantly improve classification accuracy. PD, MSA, PSP and CBD have
distinct patterns of dopaminergic depletion on (123)I-ioflupane SPECT. The high
specificity of 84-90% for PD versus APS indicates that the classifier is
particularly useful for confirming APS cases.
PMID- 27489774
TI - LGI1-negative faciobrachial dystonic-like seizures originating from the insula.
AB - We expand the differential diagnosis of LGI1-positive faciobrachial dystonic
seizures (FBDS) by presenting a 67-year-old woman affected by seizures of similar
semiology who was found to have insular epilepsy. We report the distinct
characteristics of insular faciobrachial dystonic-like seizures that would help
clinicians to differentiate them from typical LGI1-positive FBDS, thus, guiding
therapy while awaiting antibody results. LGI1-negative faciobrachial dystonic
like seizures should be considered when the seizure semiology includes unilateral
and prolonged dystonia without loss of awareness, there is an ictal EEG
correlate, MRI is suggestive of insular lesion, and when there is neither clearly
associated memory impairment nor hyponatremia.
PMID- 27489772
TI - Automated detection of cerebral microbleeds in patients with Traumatic Brain
Injury.
AB - In this paper a Computer Aided Detection (CAD) system is presented to
automatically detect Cerebral Microbleeds (CMBs) in patients with Traumatic Brain
Injury (TBI). It is believed that the presence of CMBs has clinical prognostic
value in TBI patients. To study the contribution of CMBs in patient outcome,
accurate detection of CMBs is required. Manual detection of CMBs in TBI patients
is a time consuming task that is prone to errors, because CMBs are easily
overlooked and are difficult to distinguish from blood vessels. This study
included 33 TBI patients. Because of the laborious nature of manually annotating
CMBs, only one trained expert manually annotated the CMBs in all 33 patients. A
subset of ten TBI patients was annotated by six experts. Our CAD system makes use
of both Susceptibility Weighted Imaging (SWI) and T1 weighted magnetic resonance
images to detect CMBs. After pre-processing these images, a two-step approach was
used for automated detection of CMBs. In the first step, each voxel was
characterized by twelve features based on the dark and spherical nature of CMBs
and a random forest classifier was used to identify CMB candidate locations. In
the second step, segmentations were made from each identified candidate location.
Subsequently an object-based classifier was used to remove false positive
detections of the voxel classifier, by considering seven object-based features
that discriminate between spherical objects (CMBs) and elongated objects (blood
vessels). A guided user interface was designed for fast evaluation of the CAD
system result. During this process, an expert checked each CMB detected by the
CAD system. A Fleiss' kappa value of only 0.24 showed that the inter-observer
variability for the TBI patients in this study was very large. An expert using
the guided user interface reached an average sensitivity of 93%, which was
significantly higher (p = 0.03) than the average sensitivity of 77% (sd 12.4%)
that the six experts manually detected. Furthermore, with the use of this CAD
system the reading time was substantially reduced from one hour to 13 minutes per
patient, because the CAD system only detects on average 25.9 false positives per
TBI patient, resulting in 0.29 false positives per definite CMB finding.
PMID- 27489773
TI - The effective connectivity of the seizure onset zone and ictal perfusion changes
in amygdala kindled rhesus monkeys.
AB - Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded
as a circuit-level disorder that cannot be understood outside this context.
Better insight into the effective connectivity of the seizure onset zone and the
manner in which seizure activity spreads could lead to specifically-tailored
therapies for epilepsy. We applied the electrical amygdala kindling model in two
rhesus monkeys until these animals displayed consistent stage IV seizures. At
this stage, we investigated the effective connectivity of the amygdala by means
of electrical microstimulation during fMRI (EM-fMRI). In addition, we imaged
changes in perfusion during a seizure using ictal SPECT perfusion imaging. The
spatial overlap between the connectivity network and the ictal perfusion network
was assessed both at the regional level, by calculating Dice coefficients using
anatomically defined regions of interest, and at the voxel level. The kindled
amygdala was extensively connected to bilateral cortical and subcortical
structures, which in many cases were connected multisynaptically to the amygdala.
At the regional level, the spatial extents of many of these fMRI activations and
deactivations corresponded to the respective increases and decreases in perfusion
imaged during a stage IV seizure. At the voxel level, however, some regions
showed residual seizure-specific activity (not overlapping with the EM-fMRI
activations) or fMRI-specific activation (not overlapping with the ictal SPECT
activations), indicating that frequently, only a part of a region anatomically
connected to the seizure onset zone participated in seizure propagation. Thus, EM
fMRI in the amygdala of electrically-kindled monkeys reveals widespread areas
that are often connected multisynaptically to the seizure focus. Seizure activity
appears to spread, to a large extent, via these connected areas.
PMID- 27489775
TI - Forced normalization's converse as nature's model for use of ECT in the
management of psychosis: An observational case series.
PMID- 27489776
TI - A cross strain Plasmodium falciparum microarray optimized for the transcriptome
analysis of Plasmodium falciparum patient derived isolates.
AB - Malarial parasite P. falciparum, an apicomplexan protozoan has a 23.3 MB nuclear
genome and encodes ~ 5600 transcripts. The genetic diversity of the parasite
within and across geographical zones is a challenge to gene expression studies
which are essential for understanding of disease process, outcome and developing
markers for diagnostics and prognostics. Here, we describe the strategy involved
in designing a custom P. falciparum 15K array using the Agilent platform and
Genotypic's Right Design methodology to study the transcriptome of Indian field
isolates for which genome sequence information is limited. The array contains
probes representing genome sequences of two distinct geographical isolates (i.e.
3D7 and HB3) and sub-telomeric var gene sequences of a third isolate (IT4) known
to adhere in culture condition. Probes in the array have been selected based on
their efficiency to detect transcripts through a 244K array experimentation.
Array performance for the 15K array, was evaluated and validated using RNA
materials from P. falciparum clinical isolates. A large percentage (91%) of the
represented transcripts was detected from Indian P. falciparum patient isolates.
Replicated probes and multiple probes representing the same gene showed perfect
correlation between them suggesting good probe performance. Additional
transcripts could be detected due to inclusion of unique probes representing HB3
strain transcripts. Variant surface antigen (VSA) transcripts were detected by
optimized probes representing the VSA genes of three geographically distinct
strains. The 15K cross strain P. falciparum array has shown good efficiency in
detecting transcripts from P. falciparum parasite samples isolated from patients.
The low parasite loads and presence of host RNA makes arrays a preferred platform
for gene expression studies over RNA-Seq.
PMID- 27489777
TI - Clinical experience with N-carbamylglutamate in a single-centre cohort of
patients with propionic and methylmalonic aciduria.
AB - BACKGROUND: The effect of long-term N-carbamylglutamate (NCG) treatment on the
rate and severity of decompensations due to propionic aciduria (PA) and
methylmalonic aciduria (MMA) is unknown. This paper presents clinical experience
from a single-centre cohort of patients with PA and MMA who received continuous
long-term treatment with NCG. METHODS: The effect of oral NCG treatment (initial
dose: 50 mg/kg/day) was investigated in patients with PA or MMA who were
experiencing frequent progressive episodes of metabolic decompensation, who had
pathological levels of ammonia, and who were referred to the Division of
Metabolic Diseases, University Hospital of Padova between August 2014 and
December 2015. Clinical and biochemical data, including the number of metabolic
decompensations, lactic acid, uric acid and plasma ammonia levels, protein intake
and body weight, were collected before and after the initiation of NCG treatment.
RESULTS: Eight patients with PA (n = 4) and MMA (n = 4) aged 2-20 years were
treated with NCG (50 mg/kg/day) for 7-16 months. Metabolic decompensation
episodes decreased in number and severity, with three of the patients having no
episodes (pre-treatment: 24 episodes; post-treatment: 9 episodes). After NCG
treatment, all episodes were treated at home and none required hospitalisation,
lactic acid values were 1.3-2.1 mmol/L and uric acid values were 0.21-0.36
mmol/L. Significant reductions in blood ammonia levels after NCG initiation were
observed in five patients, whereas levels were reduced or maintained in the
normal range in the remainder. Over the treatment period, patients had an
increase in natural protein intake of 20-50% and gained 0-6.5 kg in bodyweight.
CONCLUSION: These observations suggest that, in addition to short-term benefits
for the acute treatment of hyperammonaemia, NCG may be effective and well
tolerated as a long-term treatment in patients with severe PA and MMA, and that
further prospective studies are warranted.
PMID- 27489778
TI - The influence of a polymorphism in the gene encoding angiotensin converting
enzyme (ACE) on treatment outcomes in late-onset Pompe patients receiving
alglucosidase alfa.
AB - Correlations between angiotensin-converting enzyme (ACE) genotype (I/I, I/D,
D/D), disease severity at baseline and response to enzyme replacement therapy
(ERT) were assessed in the Pompe disease Late-Onset Treatment Study (LOTS). No
correlations were observed between ACE genotype and disease severity at baseline.
However, D/D patients appeared to have a reduced response to alglucosidase alfa
treatment than I/I or I/D patients, suggesting that ACE polymorphisms may
influence the response to alglucosidase alfa treatment and warrants further
investigation.
PMID- 27489779
TI - Gross Findings of Widespread Visceral Metastasis of Prostatic Adenocarcinoma With
Neuroendocrine Features: A Case Report.
AB - Although prostate cancer is common in the western world and is associated with
favorable overall survival, neuroendocrine prostate cancer is difficult to detect
and is known to aggressively metastasize throughout the body. This subset of
disease thus has a poor prognosis, and early detection and treatment of
neuroendocrine prostate cancer may increase overall survival. We present a case
of a now deceased 63 year old male with extensive epicardial, respiratory, hepato
bilary, adrenal, genitourinary, and osseous tissue metastasis.
PMID- 27489780
TI - A landscape-based cluster analysis using recursive search instead of a threshold
parameter.
AB - Cluster-based analysis methods in neuroimaging provide control of whole-brain
false positive rates without the need to conservatively correct for the number of
voxels and the associated false negative results. The current method defines
clusters based purely on shapes in the landscape of activation, instead of
requiring the choice of a statistical threshold that may strongly affect results.
Statistical significance is determined using permutation testing, combining both
size and height of activation. A method is proposed for dealing with relatively
small local peaks. Simulations confirm the method controls the false positive
rate and correctly identifies regions of activation. The method is also
illustrated using real data. *A landscape-based method to define clusters in
neuroimaging data avoids the need to pre-specify a threshold to define
clusters.*The implementation of the method works as expected, based on simulated
and real data.*The recursive method used for defining clusters, the method used
for combining clusters, and the definition of the "value" of a cluster may be of
interest for future variations.
PMID- 27489781
TI - A genetically encoded bioluminescent indicator for illuminating proinflammatory
cytokines.
AB - We introduce a method to evaluate the activities of cytokines based on the
nuclear transport of NF-kappaB. A pair of bioluminescent indicators was made for
conferring cytokine sensitivity to cervical carcinoma-derived HeLa cells. The
principle is based on reconstitution of split fragments of Renilla reniformis
luciferase (RLuc) by protein splicing with a DnaE intein from Synechocystis sp.
PCC6803. The bioluminescence intensity of thus reconstituted RLuc in the HeLa
cells was used as a measure of the activities for cytokines. With the present
method, we evaluated the activities of various cytokines based on the nuclear
transport of NF-kappaB in human cervical carcinoma-derived HeLa cells carrying
the indicators. The present approach to evaluating the activities of cytokines
may provide a potential clinical value in monitoring drug activity and directing
treatment for various diseases related with NF-kappaB. The method highlights the
experimental procedure from our original publications, Anal. Biochem. 2006, 359,
147-149 and Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 11542. The summary of the
method is: *Cytokine activities are determined within 2 h after
stimulation.*Temporarily inactivated split-luciferase fragments are reconstituted
by protein splicing.*Nucleartrafficking of NF-kappaB was illuminated for gauging
the ligand-driven activity.
PMID- 27489783
TI - Qatar Medical Journal at the forefront of medical publishing.
PMID- 27489782
TI - Exercise reduces depressive symptoms in adults with arthritis: Evidential value.
AB - AIM: To determine whether evidential value exists that exercise reduces
depression in adults with arthritis and other rheumatic conditions. METHODS:
Utilizing data derived from a prior meta-analysis of 29 randomized controlled
trials comprising 2449 participants (1470 exercise, 979 control) with
fibromyalgia, osteoarthritis, rheumatoid arthritis or systemic lupus
erythematosus, a new method, P-curve, was utilized to assess for evidentiary
worth as well as dismiss the possibility of discriminating reporting of
statistically significant results regarding exercise and depression in adults
with arthritis and other rheumatic conditions. Using the method of Stouffer, Z
scores were calculated to examine selective-reporting bias. An alpha (P) value <
0.05 was deemed statistically significant. In addition, average power of the
tests included in P-curve, adjusted for publication bias, was calculated.
RESULTS: Fifteen of 29 studies (51.7%) with exercise and depression results were
statistically significant (P < 0.05) while none of the results were statistically
significant with respect to exercise increasing depression in adults with
arthritis and other rheumatic conditions. Right-skew to dismiss selective
reporting was identified (Z = -5.28, P < 0.0001). In addition, the included
studies did not lack evidential value (Z = 2.39, P = 0.99), nor did they lack
evidential value and were P-hacked (Z = 5.28, P > 0.99). The relative frequencies
of P-values were 66.7% at 0.01, 6.7% each at 0.02 and 0.03, 13.3% at 0.04 and
6.7% at 0.05. The average power of the tests included in P-curve, corrected for
publication bias, was 69%. Diagnostic plot results revealed that the observed
power estimate was a better fit than the alternatives. CONCLUSION: Evidential
value results provide additional support that exercise reduces depression in
adults with arthritis and other rheumatic conditions.
PMID- 27489784
TI - Advances in technology are changing the future of medicine.
PMID- 27489785
TI - Allergen-specific immunotherapy in pediatric allergic asthma.
AB - Allergen-specific immunotherapy (AIT) is the only curative way that can change
the immunologic response to allergens and thus can modify the natural progression
of allergic diseases. There are some important criteria which contributes
significantly on efficacy of AIT, such as the allergen extract used for
treatment, the dose and protocol, patient selection in addition to the severity
and control of asthma. The initiation of AIT in allergic asthma should be
considered in intermittent, mild and moderate cases which coexisting with other
allergic diseases such as allergic rhinitis, and in case of unacceptable adverse
effects of medications. Two important impact of AIT; steroid sparing effect and
preventing from progression to asthma should be taken into account in pediatric
asthma when making a decision on starting of AIT. Uncontrolled asthma remains a
significant risk factor for adverse events and asthma should be controlled both
before and during administration of AIT. The evidence concerning the efficacy of
subcutaneous (SCIT) and sublingual immunotherapy (SLIT) for treatment of
pediatric asthma suggested that SCIT decreases asthma symptoms and medication
scores, whereas SLIT can ameliorate asthma symptoms. Although the effectiveness
of SCIT has been shown for both seasonal and perennial allergens, the data for
SLIT is less convincing for perennial allergies in pediatric asthma.
PMID- 27489786
TI - Supporting the validation of the new allergic and hypersensitivity conditions
section of the World Health Organization International Classification of Diseases
11.
AB - BACKGROUND: The new International Classification of Diseases (ICD)-11 "Allergic
and hypersensitivity conditions" section has been constructed as a result of a
detailed and careful action plan based on scientific evidences for the necessity
of changes and collaboration with the World Health Organization (WHO) ICD-11
revision governance. All the efforts are being acknowledged by the Joint Allergy
Academies. OBJECTIVE: Considering the new classification model addressed to the
allergic and hypersensitivity conditions and following the ICD WHO agenda, we
believe it is the appropriate time to start supporting the validation process in
collaboration with the WHO ICD governance. METHODS: We conducted a mapping of ICD
10 allergic and hypersensitivity conditions in the ICD-11 beta phase structure
and categorized the conditions as fitting by "precoordination,"
"postcoordination," "indexed to the ICD-11 Foundation," "no code fit properly" or
"no correspondence" in the ICD-11. RESULTS: From overall 125 ICD-10 entities
spread in 6 chapters, 57.6% were able to be precoordinated, 4% postcoordinated,
12% indexed to the Foundation, 9.6% had no code fitting properly and 18.6% had no
correspondence in the ICD-11 framework. CONCLUSION: We have been able to
demonstrate that 83.2% of the ICD-10 allergic and hypersensitivity conditions
could be captured by the current ICD-11 beta draft framework. We strongly believe
that our findings constitute a key step forward for a softer transition of the
ICD-10 allergic and hypersensitivity conditions to the ICD-11, supporting the WHO
in this process as well as strengthening the visibility of the Allergy specialty
and ensuring quality management of allergic patients.
PMID- 27489788
TI - The efficacy of single premedication with antihistamines for radiocontrast media
hypersensitivity.
AB - BACKGROUND: Single premedication with antihistamines for radiocontrast media
(RCM) hypersensitivity is frequently used in real world at the emergent situation
although its efficacy is not proven. OBJECTIVE: To evaluate the effect of
intravenous antihistamines as a premedication in general population who had
experience of mild adverse reactions to iodinated RCM. METHODS: A retrospective
observational study on 14,785 subjects who had RCM-enhanced computed tomography
scans between January 2014 and December 2015 in Seoul National University
Hospital Gangnam Healthcare Center, Seoul, South Korea. RESULTS: Among 453
subjects who had a history of mild RCM-induced hypersensitivity reactions, 273
subjects had a single premedication of intravenous antihistamine. When comparing
antihistamine-premedication group and nonpremedication group, there is no
protective effect of antihistamines on the incidence rate and severity of
hypersensitivity (10.6% vs. 11.7%, p = 0.729). CONCLUSION: The clinical efficacy
of a single premedication of antihistamines for mild RCM-induced hypersensitivity
was not confirmed.
PMID- 27489787
TI - Relationship between all fevers or fever after vaccination, and atopy and atopic
disorders at 18 and 36 months.
AB - BACKGROUND: Studies have reported that early febrile episodes and febrile
episodes with infections are associated with a decreased risk of developing
atopy. OBJECTIVE: To examine further the association between presence of and
number of febrile episodes are with atopy and atopic diseases and if there was a
difference between all fevers and fever after vaccination. METHODS: We studied
448 infants in a Singapore mother-offspring cohort study (Growing Up in Singapore
Towards Healthy Outcomes) which had complete data for the exposures and outcomes
of interest. Fever was defined as more than 38.0C and was self-reported. The
presence of and number of febrile episodes were examined for association with
outcome measures, namely parental reports of doctor-diagnosed asthma and eczema,
and rhinitis, which was evaluated by doctors involved in the study at 18 and 36
months. These outcomes were considered atopic if there were 1 or more positive
skin prick tests. RESULTS: The presence of all fevers from 0-6 months of age was
associated with reduced odds of having atopy at 36 months of age (unadjusted odds
ratio [OR], 0.628; 95% confidence interval [CI], 0.396-0.995). The presence of
fever after vaccination from 0-24 months of age was associated with reduced odds
of having atopy at 36 months of age (OR, 0.566; 95% CI, 0.350-0.915). The
presence of all fevers from 0-6 months of age was associated with reduced odds of
having atopic eczema at 36 months (OR, 0.430; 95% CI, 0.191-0.970). Fever was
associated with increased odds of having doctor-diagnosed asthma and rhinitis.
CONCLUSION: There was an inverse relationship between the presence of all fevers
from 0-6 months of age and the development of atopy and eczema at 36 months of
age. Fever after vaccination might be considered a subclinical infection that did
not show the same effect in early life.
PMID- 27489789
TI - Effect on quality of life of the mixed house dust mite/weed pollen extract
immunotherapy.
AB - BACKGROUND: Although many patients with allergic rhinitis have symptoms due to
sensitization to more than one kind of allergens, and mixed allergen extracts are
widely used for immunotherapy, there are few published trials. OBJECTIVE: Our
study aimed to evaluate the effect of multiple-allergen immunotherapy on
improving the symptoms and quality of life of allergic rhinitis patients.
METHODS: We performed a 1-year single-center observation study of subcutaneous
immunotherapy using house dust mite extract (n = 12), weed pollen extract (n =
21), or mixed house dust mite/weed pollen extract (n = 11) in 44 allergic
rhinitis patients. All the allergens responsible for the symptom of each patient
were included in his immunotherapy. Symptom score, medication score, and quality
of life of the patients were evaluated before and after 1-year immunotherapy.
Quality of life was evaluated with the Rhinoconjunctivitis Quality of Life
Questionnaire. RESULTS: In all 3 groups receiving subcutaneous immunotherapy,
significant improvement of symptom score, medication score, and quality of life
was found vs. baseline at 1 year, irrespective of the allergen used. In the weed
pollen season, the changes of quality of life questionnaire score after 1-year
treatment were not significantly different between the weed pollen group (1.55 +/
1.24) and the mixed house dust mite/weed pollen group (1.14 +/- 1.01). The same
happened in the nonpollen seasons, during which dust mite immunotherapy (1.23 +/-
1.63) and mixed immunotherapy (0.60 +/- 0.47) did not show significantly
different effect on the quality of life. CONCLUSION: The multiple-allergen
immunotherapy might be effective in polysensitized allergic rhinitis patients,
and could improve their quality of life. Our result did not show significant
difference between the effects of multiple-allergen immunotherapy and mono
allergen immunotherapy.
PMID- 27489790
TI - Feasibility of a smartphone application based action plan and monitoring in
asthma.
AB - BACKGROUND: Asthma patients may experience acute episodic exacerbation. The
guidelines recommend that written action plan should be given to asthma patients.
However, no one can predict when and where acute exacerbation will happen. As
people carry smart phone almost anytime and anywhere, smartphone application
could be a useful tool in asthma care. We evaluated the feasibility of the
ubiquitous healthcare system of asthma care using a smartphone application
(snuCare) based on the self-management guideline or action plan. METHODS: Forty
four patients including fragile asthmatics were enrolled from Seoul National
University Bundang Hospital between December 2011 and February 2012. They were
randomly assigned into application user (n = 22) or application nonuser group (n
= 22). We evaluated user-satisfaction, and clinical parameters such as asthma
control, Quality of Life Questionnaire for Adult Korean Asthmatics, and the
adherence of patients. RESULTS: The characteristics were similar at baseline
between the 2 groups except those who treated with short-term systemic steroid or
increased dose of systemic steroid during previous 8 weeks (user vs. nonuser:
31.8% vs. 4.5%, p = 0.020). Total of 2,226 signals was generated during 8 weeks
including 5 risky states. After eight weeks, the users answered that it was very
easy to use the application, which was shown in highest scores in terms of
satisfaction (mean +/- standard deviation, 4.3 +/- 0.56). Seventy-three percent
of patients answered that the application was very useful for asthma care. User
group showed improved the adherence scores (p = 0.017). One patient in
application user group could avoid Emergency Department visit owing to the
application while a patient in nonuser group visited Emergency Department.
CONCLUSION: The ubiquitous healthcare system using a smartphone application
(snuCare) based on the self-management guideline or action plan could be helpful
in the monitoring and the management of asthma.
PMID- 27489791
TI - Role of eosinophilic inflammation and atopy in elderly asthmatic patients.
AB - BACKGROUND: Asthma in the elderly is severe and associated with poor treatment
outcome. Although atopy has an important role in pathogenesis, its role in the
elderly is unclear, partly due to immune senescence. OBJECTIVE: We aimed to
examine the associations of Th2-mediated inflammation with asthma severity in the
elderly. METHODS: Consecutive asthmatics older than 60 years without severe
exacerbation within 8 weeks were enrolled. Atopic status was determined by
positive serum specific IgE or skin prick test to common aeroallergens. Serum
total IgE was measured simultaneously to exhaled fractional concentration of
nitric oxide (FeNO). Asthma control level was assessed by using Thai Asthma
Control Test (ACT) score. RESULTS: Total of 44 elderly asthmatic patients were
enrolled. The mean age was 68.9 years and mean age of asthma diagnosis was 46.6
years. Seventy-seven percent of patients were female. Atopic status was found in
45.5% of patients. Uncontrolled asthma classified as ACT score < 20 was noted in
25% of elderly asthma, but its association with either high serum total IgE
(>=120 IU/mL), high FeNO (>=50 ppb) or atopic status was not detected.
CONCLUSION: One-fourth of elderly asthmatics were clinically uncontrolled, while
atopy was confirmed in 45.5%. Neither high total IgE, high FeNO nor atopic status
was associated with uncontrolled asthma in the elderly. Other factors might play
role in asthma severity in the elderly, and has to be further investigated.
PMID- 27489792
TI - Delayed diagnosis of allergic bronchopulmonary aspergillosis due to absence of
asthmatic symptoms.
AB - Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease with small
prevalence. Exposure to aspergillus mold causes immunologic hypersensitivity and
may cause ranges of symptoms from minimal to detrimental outcomes. Diagnosing and
treating the disease before the development of bronchiectasis may save the
patient from poor outcomes. This report presents a case of recurrent ABPA without
any symptom of asthma, which impeded the correct diagnosis even after numerous
hospitalizations.
PMID- 27489793
TI - Marking nut anaphylaxis.
AB - Marking nut Semecarpus anacardium, so-called because it contains a pigment that
has been used in the past to mark fabrics, is a known cause of contact
hypersensitivity. It may be ingested as an ingredient of some traditional Hindi
foods. We describe the first reported case of anaphylaxis to marking nut.
PMID- 27489794
TI - Proctitis 1 Week after Stereotactic Body Radiation Therapy for Prostate Cancer:
Implications for Clinical Trial Design.
AB - BACKGROUND: Proctitis following prostate cancer radiation therapy is a primary
determinant of quality of life (QOL). While previous studies have assessed acute
rectal morbidity at 1 month after stereotactic body radiotherapy (SBRT), little
data exist on the prevalence and severity of rectal morbidity within the first
week following treatment. This study reports the acute bowel morbidity 1 week
following prostate SBRT. MATERIALS AND METHODS: Between May 2013 and August 2014,
103 patients with clinically localized prostate cancer were treated with 35-36.25
Gy in five fractions using robotic SBRT delivered on a prospective clinical
trial. Bowel toxicity was graded using the Common Terminology Criteria for
Adverse Events version 4.0 (CTCAEv.4). Bowel QOL was assessed using the EPIC-26
questionnaire bowel domain at baseline, 1 week, 1 month, and 3 months. Time
dependent changes in bowel symptoms were statistically compared using the
Wilcoxon signed-rank test. Clinically significant change was assessed by the
minimally important difference (MID) in EPIC score. This was defined as a change
of 1/2 standard deviation (SD) from the baseline score. RESULTS: One-hundred and
three patients with a minimum of 3 months of follow-up were analyzed. The
cumulative incidence of acute grade 2 gastrointestinal (GI) toxicity was 23%.
There were no acute >= grade 3 bowel toxicities. EPIC bowel summary scores
maximally declined at 1 week after SBRT (-13.9, p < 0.0001) before returning to
baseline at 3 months after SBRT (+0.03, p = 0.94). Prior to treatment, 4.9% of
men reported that their bowel bother was a moderate to big problem. This
increased to 28.4% (p < 0.0001) 1 week after SBRT and returned to baseline at 3
months after SBRT (0.0%, p = 0.66). Only the bowel summary and bowel bother score
declines at 1 week met the MID threshold for clinically significant change.
CONCLUSION: The rate and severity of acute proctitis following prostate SBRT
peaked at 1 week after treatment and returned to baseline by 3 months. Toxicity
assessment at 1 week can therefore minimize recall bias and should aid in the
design of future clinical trials focused on accurately capturing and minimizing
acute morbidity following SBRT.
PMID- 27489795
TI - Bone Marrow Immunity and Myelodysplasia.
AB - Myelodysplastic syndrome (MDS) is characterized by an ineffective hematopoiesis
with production of aberrant clones and a high cell apoptosis rate in bone marrow
(BM). Macrophages are in charge of phagocytosis. Innate Immune cells and specific
T cells are in charge of immunosurveillance. Little is known on BM cell
recruitment and activity as BM aspirate is frequently contaminated with
peripheral blood. But evidences suggest an active role of immune cells in
protection against MDS and secondary leukemia. BM CD8(+) CD28(-) CD57(+) T cells
are directly cytotoxic and have a distinct cytokine signature in MDS, producing
TNF-alpha, IL-6, CCL3, CCL4, IL-1RA, TNFalpha, FAS-L, TRAIL, and so on. These
tools promote apoptosis of aberrant cells. On the other hand, they also increase
MDS-related cytopenia and myelofibrosis together with TGFbeta. IL-32 produced by
stromal cells amplifies NK cytotoxicity but also the vicious circle of TNFalpha
production. Myeloid-derived suppressing cells (MDSC) are increased in MDS and
have ambiguous role in protection/progression of the diseases. CD33 is expressed
on hematopoietic stem cells on MDS and might be a potential target for
biotherapy. MDS also has impact on immunity and can favor chronic inflammation
and emergence of autoimmune disorders. BM is the site of hematopoiesis and thus
contains a complex population of cells at different stages of differentiation
from stem cells and early engaged precursors up to almost mature cells of each
lineage including erythrocytes, megakaryocytes, myelo-monocytic cells
(monocyte/macrophage and granulocytes), NK cells, and B cells. Monocytes and B
cell finalize their maturation in peripheral tissues or lymph nodes after
migration through the blood. On the other hand, T cells develop in thymus and are
present in BM only as mature cells, just like other well vascularized tissues. BM
precursors have a strong proliferative capacity, which is usually associated with
a high risk for genetic errors, cell dysfunction, and consequent cell death.
Abnormal cells are prone to destruction through spontaneous apoptosis or because
of the immunosurveillance that needs to stay highly vigilant. High rates of
proliferation or differentiation failures lead to a high rate of cell death and
massive release of debris to be captured and destroyed (1). Numerous macrophages
reside in BM in charge of home-keeping. They have a high capacity of phagocytosis
required for clearing all these debris.
PMID- 27489797
TI - Emergence of Plasmid-Borne dfrA14 Trimethoprim Resistance Gene in Shigella
sonnei.
AB - The most common mechanism of trimethoprim (TMP)-resistance is the acquisition of
dihydrofolate reductase enzyme resistant to this drug. Previous molecular
characterization of TMP-genes resistance in Chilean isolates of Shigella sonnei
searching for dfrA1 and dfrA8, showed solely the presence of dfrA8 (formerly
dhfrIIIc). However, these genetic markers were absent in S. sonnei strains
further isolated during an outbreak in 2009. To identify the TMP-resistance gene
in these strains, a genomic DNA library from a TMP-resistant (TMP(R)) S. sonnei
representative strain for the outbreak was used to clone, select and identify a
TMP-resistance marker. The TMP(R) clone was sequenced by primer walking,
identifying the presence of the dfrA14 gene in the sul2-strA'-dfrA14-'strA-strB
gene arrangement, harbored in a native 6779-bp plasmid. The same plasmid was
isolated by transforming with a ~4.2 MDa plasmid extracted from several TMP(R) S.
sonnei strains into Escherichia coli. This plasmid, named pABC-3, was present
only in dfrA14-positive strains and was homologous to a previously described
pCERC-1, but different due to the absence of an 11-bp repetitive unit. The
distribution of dfrA1, dfrA8, and dfrA14 TMP-resistance genes was determined in
126 TMP(R) S. sonnei isolates. Most of the strains (96%) carried only one of the
three TMP-resistance genes assessed. Thus, all strains obtained during the 2009
outbreak harbored only dfrA14, whereas, dfrA8 was the most abundant gene marker
before outbreak and, after the outbreak dfrA1 seems have appeared in circulating
strains. According to PFGE, dfrA14-positive strains were clustered in a
genetically related group including some dfrA1- and dfrA8-positive strains;
meanwhile other genetic group included most of the dfrA8-positive strains. This
distribution also correlated with the isolation period, showing a dynamics of
trimethoprim genetic markers prevalent in Chilean S. sonnei strains. To our
knowledge, dfrA14 gene associated to a small non-conjugative plasmid was detected
for the first time in Shigella. Apparently, the strain causing the outbreak must
have been introduced, changing drastically the genetic distribution of
trimethoprim resistance in Chilean S. sonnei strains.
PMID- 27489798
TI - Prospects for dengue vaccines for travelers.
AB - Travel-acquired dengue cases have been increasing as the overall global dengue
burden has expanded. In Korea, imported dengue cases have been reported since
2000 when it first became a notifiable disease. During the first four months of
2016, three times more dengue cases were reported in Korea than during the same
period the previous year. A safe and efficacious vaccine for travelers would be
beneficial to prevent dengue disease in individual travelers and potentially
decrease the risk of virus spread to non-endemic areas. Here, we summarize the
characteristics of dengue vaccines for travelers and review dengue vaccines
currently licensed or in clinical development.
PMID- 27489796
TI - Modification of Bacterial Effector Proteins Inside Eukaryotic Host Cells.
AB - Pathogenic bacteria manipulate their hosts by delivering a number of virulence
proteins -called effectors- directly into the plant or animal cells. Recent
findings have shown that such effectors can suffer covalent modifications inside
the eukaryotic cells. Here, we summarize the recent reports where effector
modifications by the eukaryotic machinery have been described. We restrict our
focus on proteins secreted by the type III or type IV systems, excluding other
bacterial toxins. We describe the known examples of effectors whose enzymatic
activity is triggered by interaction with plant and animal cell factors,
including GTPases, E2-Ubiquitin conjugates, cyclophilin and thioredoxins. We
focus on the structural interactions with these factors and their influence on
effector function. We also review the described examples of host-mediated post
translational effector modifications which are required for proper subcellular
location and function. These host-specific covalent modifications include
phosphorylation, ubiquitination, SUMOylation, and lipidations such as
prenylation, fatty acylation and phospholipid binding.
PMID- 27489799
TI - Accelerating the development of a group A Streptococcus vaccine: an urgent public
health need.
AB - Group A Streptococcus (GAS) infections cause substantial worldwide morbidity and
mortality, mostly associated with suppurative complications such as pharyngitis,
impetigo, and non-suppurative immune syndromes such as acute rheumatic fever,
rheumatic heart disease, and acute post-streptococcal glomerulonephritis. Deaths
occur mostly in children, adolescents, and young adults in particular pregnant
women in low- and middle-income countries. GAS strains are highly variable, and a
GAS vaccine would need to overcome the issue of multiple strains. Several
approaches have been used multivalent vaccines using N-terminal polypeptides of
different M protein; conserved M protein vaccines with antigens from the
conserved C-repeat portion of the M protein; incorporation selected T- and B-cell
epitopes from the C-repeat region in a synthetic polypeptide or shorter single
minimal B-cell epitopes from this same region; and non-M protein approaches
utilizing highly conserved motives of streptococcal C5a peptidase, GAS
carbohydrate and streptococcal fibronectin-binding proteins. A GAS vaccine
represents urgent need for this neglected disease and should therefore deserve
the greatest attention of international organizations, donors, and vaccine
manufacturers.
PMID- 27489800
TI - Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection.
AB - Johne's disease or paratuberculosis is a chronic debilitating disease in
ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The
disease causes significant economic losses in livestock industries worldwide.
There are no effective control measures to eradicate the disease because there
are no appropriate diagnostic methods to detect subclinically infected animals.
Therefore, it is very difficult to control the disease using only test and cull
strategies. Vaccination against paratuberculosis has been considered as an
alternative strategy to control the disease when combined with management
interventions. Understanding host-pathogen interactions is extremely important to
development of vaccines. It has long been known that Th1-mediated cellular immune
responses are play a crucial role in protection against MAP infection. However,
recent studies suggested that innate immune responses are more closely related to
protective effects than adaptive immunity. Based on this understanding, several
attempts have been made to develop vaccines against paratuberculosis. A variety
of ideas for designing novel vaccines have emerged, and the tests of the efficacy
of these vaccines are conducted constantly. However, no effective vaccines are
commercially available. In this study, studies of the development of vaccines for
MAP were reviewed and summarized.
PMID- 27489801
TI - Influenza virus vaccine for neglected hosts: horses and dogs.
AB - This study provides information regarding vaccine research and the epidemiology
of influenza virus in neglected hosts (horses and dogs). Equine influenza virus
(EIV) causes a highly contagious disease in horses and other equids, and
outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse
industry and has the ability of cross the host species barrier from horses to
dogs. Canine influenza is a virus of equine or avian origin and infects companion
animals that live in close contact with humans; this results in possible exposure
to the seasonal epizootic influenza virus. There have been case reports of
genetic reassortment between human and canine influenza viruses, which results in
high virulence and the ability of transmission to ferrets. This emphasizes the
need for vaccine research on neglected hosts to update knowledge on current
strains and to advance technology for controlling influenza outbreaks for public
health.
PMID- 27489802
TI - Vaccination strategies in patients with solid organ transplant: evidences and
future perspectives.
AB - Solid organ transplant recipients need emphases on immunization that result in
certainly decrease the risk of vaccine preventable diseases. Organ transplant
candidate should complete the recommended full vaccination schedule as early as
possible during the courses of underlying disease because the patients with end
stage liver or renal disease have reduced immune response to vaccine.
Furthermore, live attenuated vaccines are generally contraindicated after
transplantation. This review summarizes current information and the evidences
regarding the efficacy and safety of immunization in adult solid organ transplant
candidates and recipients.
PMID- 27489803
TI - An oral Aujeszky's disease vaccine (YS-400) induces neutralizing antibody in
pigs.
AB - PURPOSE: Aujeszky's disease (AD) is an economically important disease affecting
both wild and domestic pigs of the species Sus scrofa. A previous study yielded
serological evidence of AD in Korean wild boars, which could spread AD to other
animals. A new Aujeszky's disease virus (ADV) bait vaccine is required to prevent
AD outbreaks in swine. In the present study, we investigated the safety and
immunogenicity of a gE-deleted marker vaccine, strain YS-400, in young domestic
pigs. MATERIALS AND METHODS: The YS-400 strain was propagated in Vero cells, and
the trial ADV bait vaccine (a vaccine blister in a matrix including an
attractant) was prepared. Pigs were orally immunized with the vaccine (2 mL,
10(7.5) TCID50/mL) delivered using a syringe or in the bait vaccine. The animals
were observed for 9 weeks after vaccination, and immunogenicity was assessed
using a virus neutralization (VN) test and enzyme linked immunosorbent assay.
RESULTS: The YS-400 strain was non-pathogenic to pigs when given orally and
induced high VN titers (1:32-1:128) 6 weeks post-administration. Of the pigs
given the ADV bait vaccine twice or three times, 40% were seropositive by 2
weeks, and 100% were seropositive by 7 weeks after the first dose. Pigs that
consumed the AD bait vaccine three times developed VN titers that were slightly
higher than those of pigs given the vaccine twice. CONCLUSION: Domestic pigs
given the trial ADV bait vaccine exhibited no adverse effects and developed high
VN titers against ADV, indicating that the YS-400 strain is safe and can prevent
ADV infection in domestic pigs.
PMID- 27489804
TI - QS-21 enhances the early antibody response to oil adjuvant foot-and-mouth disease
vaccine in cattle.
AB - PURPOSE: One of the most important tools against foot-and-mouth disease, a highly
contagious and variable viral disease of cloven-hoofed animals, is vaccination.
However, the effectiveness of foot-and-mouth disease vaccines on slowing the
spread of the disease is questionable. In contrast, high potency vaccines
providing early protection may solve issues with the spread of the disease,
escaping mutants, and persistency. To increase the potency of the vaccine,
additives such as saponin and aluminium hydroxide are used. However, the use of
saponin with an oil adjuvant is not common and is sometimes linked to toxicity.
QS-21, which is less toxic than Quil A, has been presented as an alternative for
use with saponin. In this study, the addition of QS-21 to a commercially
available foot-and-mouth disease water-in-oil-in-water emulsion vaccine was
evaluated in cattle. MATERIALS AND METHODS: After vaccination, serum samples were
collected periodically over 3 months. Sera of the QS-21 and normal oil vaccine
groups were compared via serum virus neutralization antibody titre and liquid
phase blocking enzyme-linked immunosorbent assay antibody titre. RESULTS: The
results showed that there was a significant early antibody increase in the QS-21
group. CONCLUSION: Strong early virus neutralizing antibody response will be
useful for emergency or ring vaccinations against foot-and-mouth disease in
target animals.
PMID- 27489805
TI - Protective efficacy and immune responses by homologous prime-booster
immunizations of a novel inactivated Salmonella Gallinarum vaccine candidate.
AB - PURPOSE: Salmonella enterica serovar Gallinarum (SG) ghost vaccine candidate was
recently constructed. In this study, we evaluated various prime-boost vaccination
strategies using the candidate strain to optimize immunity and protection
efficacy against fowl typhoid. MATERIALS AND METHODS: The chickens were divided
into five groups designated as group A (non-immunized control), group B (orally
primed and boosted), group C (primed orally and boosted intramuscularly), group D
(primed and boosted intramuscularly), and group E (primed intramuscularly and
boosted orally). The chickens were primed with the SG ghost at 7 days of age and
were subsequently boosted at the fifth week of age. Post-immunization, the plasma
IgG and intestinal secretory IgA (sIgA) levels, and the SG antigen-specific
lymphocyte stimulation were monitored at weekly interval and the birds were
subsequently challenged with a virulent SG strain at the third week post-second
immunization. RESULTS: Chickens in group D showed an optimized protection with
significantly increased plasma IgG, sIgA, and lymphocyte stimulation response
compared to all groups. The presence of CD4(+) and CD8(+) T cells and
monocyte/macrophage (M/M) in the spleen, and splenic expression of cytokines such
as interferon gamma (IFN-gamma) and interleukin 6 (IL-6) in the immunized
chickens were investigated. The prime immunization induced significantly higher
splenic M/M population and mRNA levels of IFN-gamma whereas the booster showed
increases of splenic CD4(+) and CD8(+) T-cell population and IL-6 cytokine in
mRNA levels. CONCLUSION: Our results indicate that the prime immunization with
the SG ghost vaccine induced Th1 type immune response and the booster elicited
both Th1- and Th2-related immune responses.
PMID- 27489806
TI - Safety and immunogenicity of recombinant rabies virus (ERAGS) in mice and raccoon
dogs.
AB - PURPOSE: The development of a genetically modified live rabies vaccine applicable
to wild raccoon dogs is necessary for the eradication of rabies in Korea. Thus,
we constructed a recombinant rabies virus (RABV) called the ERAGS strain, using a
reverse genetic system and evaluated its safety and efficacy in mice and its
safety and immunogenicity in raccoon dogs. MATERIALS AND METHODS: ERAGS, which
has Asn194Ser and Arg333Glu substitutions in the glycoprotein, was constructed
using site-directed mutagenesis. Mice were inoculated with the ERAGS strain
(either 10(5.0) or 10(7.0) FAID50/mL) via intramuscular (IM) or intracranial
injections and then challenged with a virulent RABV. Raccoon dogs were
administered the ERAGS strain (10(8.0) FAID50/mL) either orally or via the IM
route and the immunogenicity of the strain was evaluated using fluorescent
antibody virus neutralization tests. RESULTS: The ERAGS strain inoculated into
murine neuroblastoma cells reached 10(7.8) FAID50/mL at 96-hour post-inoculation.
The virus was not pathogenic and induced complete protection from virulent RABV
in immunized 4- and 6-week-old mice. Korean raccoon dogs immunized with the ERAGS
strain via IM or oral route were also safe from the virus and developed high
titer levels (26.4-32.8 IU/mL) of virus-neutralizing antibody (VNA) at 4 weeks
post-inoculation. CONCLUSION: The ERAGS RABV strain was effectively protective
against rabies in mice and produced a high VNA titer in raccoon dogs.
PMID- 27489807
TI - A recombinant rabies virus (ERAGS) for use in a bait vaccine for swine.
AB - PURPOSE: Rabies viruses (RABV) circulating worldwide in various carnivores
occasionally cause fatal encephalitis in swine. In this study, the safety and
immunogenicity of a recombinant rabies virus, the ERAGS strain constructed with a
reverse genetics system, was evaluated in domestic pigs. MATERIALS AND METHODS:
Growing pigs were administered 1 mL (10(8.0) FAID50/mL) of the ERAGS strain via
intramuscular (IM) or oral routes and were observed for 4 weeks' post
inoculation. Three sows were also inoculated with 1 mL of the ERAGS strain via
the IM route. The safety and immunogenicity in swine were evaluated using daily
observation and a virus-neutralizing assay (VNA). Fluorescent antibody tests
(FAT) for the RABV antigen and reverse transcriptase-polymerase chain reaction
(RT-PCR) assays for the detection of the nucleocapsid (N) gene of RABV were
conducted with brain tissues from the sows after necropsy. RESULTS: The growing
pigs and sows administered the ERAGS strain did not exhibit any clinical sign of
rabies during the test period test and did develop VNA titers. The growing pigs
inoculated with the ERAGS strain via the IM route showed higher VNA titers than
did those receiving oral administration. FAT and RT-PCR assays were unable to
detect RABV in several tissues, including brain samples from the sows.
CONCLUSION: Our results suggest that the ERAGS strain was safe in growing pigs
and sows and induced moderate VNA titers in pigs.
PMID- 27489808
TI - A Bordetella pertussis proteoliposome induces protection in mice without
affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent
formulation.
AB - In this study, a formulation of Bordetella pertussis proteoliposome (PLBp),
diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent
vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using
the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto
assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus
whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as
controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total
reduction of CFU in lungs 7 days after intranasal challenge. Likewise,
formulations DT-PLBp, DTP, and DT elicited antibody levels >=2 IU/mL against
tetanus and diphtheria, considered protective when neutralization tests are used.
Overall, results showed that combination of PLBp with tetanus and diphtheria
toxoids did not affect the immunogenicity of each antigen alone.
PMID- 27489809
TI - Bone Healing in Ovariectomized-rabbit Calvarial Defect with Tricalcium Phosphate
Coated with Recombinant Human Bone Morphogenetic Protein-2 Genetically Engineered
in Escherichia coli.
AB - PURPOSE: This study compares the bone formation ability of tricalcium phosphate
(TCP) with and without recombinant human bone morphogenetic protein-2 (rhBMP-2)
and assesses TCP as a carrier of rhBMP-2. METHODS: Bilateral round defects
(diameter: 8.0 mm) were formed in the cranium of eight New Zealand white rabbits.
The defects were grafted with TCP only (control group) or with rhBMP-2-coated TCP
(experimental group). The animals were sacrificed at 1st week, 2nd week, 4th
week, and 8th week postoperatively; two rabbits sacrificed each time. The skulls
were harvested and subjected to radiographic and histological examination.
RESULTS: Radiologic evaluation showed faster bone remodeling in the experimental
group than in the control group. Histologic evaluation (H&E, Masson's trichrome
stain) showed rapid bone formation, remodeling and calcification in the 1st and
2nd week in the experimental group. Immunohistochemical evaluation showed higher
expression rate of osteoprotegerin, receptor activator of nuclear factor kappaB
ligand, and receptor activator of nuclear factor kappaB in the experimental group
at the 1st and 2nd week than in the control group. CONCLUSION: rhBMP-2 coated TCP
resulted in rapid bone formation, remodeling, and calcification due to rhBMP-2's
osteogenic effect. TCP performed properly as a carrier for rhBMP-2. Thus, the use
of an rhBMP-2 coating on TCP had a synergic effect on bone healing and,
especially, bone remodeling and maturation.
PMID- 27489810
TI - Bone Induction by Demineralized Dentin Matrix in Nude Mouse Muscles.
AB - PURPOSE: This study examined the osteoinductive activity of demineralized human
dentin matrix for nude mice. METHODS: Twenty healthy nude mice weighing about 15
to 20 g were used for study. Demineralized human dentin matrix was prepared and
implanted into the dorsal portion of nude mice (subcutaneous), which were
sacrificed at two, four, and eight weeks after demineralized dentin matrix
grafting and evaluated histologically by H&E and Masson trichrome staining. The
specimens were also evaluated histomorphometrically. RESULTS: The demineralized
dentin matrix induced bone and cartilage formation independently in soft tissues.
Histological examination showed bone-forming cells such as osteoblasts and
fibroblasts at two, four, and eight weeks. CONCLUSION: These results suggest that
demineralized human dentin matrix has osteoinductive ability, and is a good
alternative to autogenous bone graft materials.
PMID- 27489811
TI - Reconstruction of Defect after Treatment of Bisphosphonate-related Osteonecrois
of the Jaw with Staged Iliac Bone Graft.
AB - Bisphosphonate is used widely for osteoporosis treatment, but a rising concern is
the risk of osteonecrosis after long-term bisphosphonate use. Such cases are
increasing, suggesting a need for research to prevent and treat bisphosphonate
related osteonecrosis of jaws. A 63-year-old female took bisphosphonate
(Fosamax((r))) for four years for treatment of osteoporosis and stopped
medication two months ago because of unhealed wound. She was treated with
marginal mandibulectomy maintaining the inferior border, and a metal plate was
placed to prevent mandible fracture. Four months after the mandibulectomy,
mandible reconstruction surgery using iliac bone and allograft was done. Six
months after reconstruction, implant placement and treatment with an overdenture
was done without complications. This study presents a case with a successful
result.
PMID- 27489812
TI - Osteoradionecrosis of Jaw in Head and Neck Cancer Patient Treated with Free Iliac
Bone and Umbilical Fat Pad Graft.
AB - Osteoradionecrosis is one of the most serious complications of patients receiving
radiation therapy. It is characterized by hypovascularity, hypocellularity, and
hypoxia-inducing necrosis of bone and soft tissue following delayed healing. In
this case, a 72-year-old man was referred to the Department of Oral and
Maxillofacial Surgery complaining of trismus following extraction three months
before first visit. He had a history of right tonsillectomy, radical neck
dissection and radiotherapy performed due to right tonsillar cancer seven years
prior. After the diagnosis of osteoradionecrosis on right mandibular body and
angle, conservative antibiotic therapy was used first, but an orocutaneous
fistula gradually formed, and extensive bony destruction and sequestrum were
observed. Sequestrectomy, free particulated iliac bone and umbilical fat pad
graft were performed via a submandibular approach under general anesthesia.
Preoperative regular exams and delicate wound care led to secondary healing of
the wound without vascularized free flap reconstruction.
PMID- 27489813
TI - Cervical Necrotizing Fasciitis Caused by Dental Infection.
AB - Necrotizing fasciitis (NF) is defined as rapidly progressive necrosis of
subcutaneous fat and fascia. Although NF of the face is rare, its mortality rate
is nearly 30%. It usually originates from dental infection and can lead to
involvement of the neck, mediastinum, and chest wall. Complications resulting
from pre-existing systemic diseases can increase the mortality rate. Known
complication factors for NF include diabetes, malnutrition, advanced age,
peripheral vascular disease, renal failure, and obesity. Here, we report a case
of NF originating from dental infection in an 88-year-old woman already diagnosed
with hypertension, thoracic aortic aneurysm, and renal diseases. Such conditions
limited adequate surgical and antibiotic treatment. However, interdisciplinary
treatment involving multiple departments was implemented with good results.
PMID- 27489814
TI - Deep Neck Space Infection Caused by Keratocystic Odontogenic Tumor.
AB - Keratocystic odontogenic tumor (KCOT) is a benign cystic intraosseous tumor of
odontogenic origin. An infection of a KCOT is not common because KCOT is a benign
developmental neoplasm. Moreover, a severe deep neck space infection with
compromised airway caused by infected KCOT is rare. This report presents a 60
year-old male patient with a severe deep neck space infection related to an
infected KCOT due to cortical bone perforation and rupture of the exudate.
Treatment of the deep neck space infection and KCOT are reported.
PMID- 27489815
TI - Treatment of Temporomandibular Joint Reankylosis by Submandibular Anchorage
Technique with Temporalis Myofascial Flap.
AB - Management of temporomandibular joint (TMJ) ankylosis is challenging for the oral
and maxillofacial surgeon because it involves the mouth opening, dentofacial
deformity, diet problem, and quality of life. Although surgical techniques to
treat TMJ ankylosis have improved, reankylosis is a persistent problem. The
temporalis myofascial flap provides good material for interpositional
arthroplasty, because of its good vascular supply, anatomic proximity, and
adequate thickness. This case report examines the efficacy of submandibular
anchorage to prevent reankylosis by inhibiting flap dislocation.
PMID- 27489816
TI - Corrigendum: Osteomyelitis Treated with Antibiotic Impregnated Polymethyl
Methacrylate.
AB - [This corrects the article on p. 396 in vol. 35.].
PMID- 27489817
TI - Metastasis via Peritumoral Lymphatic Dilation in Oral Squamous Cell Carcinoma.
AB - PURPOSE: Nodal metastasis is the main prognostic factor in the patients with oral
squamous cell carcinoma (OSCC). We investigated the association between tumor
associated lymphatics and OSCC characteristics. METHODS: Thirty-four specimens
were used for the immunohistochemical staining with the antibody for vascular
endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3,
phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed
the distribution of the lymphangiogenic factors and quantified the degree of
expression. We determined lymphatic vessel density (LVD) and lymphatic vessel
dilatation with D2-40 immunostaining. We assessed the association of LVD or
lymphatic vessel dilatation with tumor progression or tumor differentiation.
RESULTS: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor,
VEGFR-3, was expressed and activated in some tumor cells as well as in tumor
associated endothelial cells. LVD was not associated with tumor size or nodal
status, but lymphatic vessel dilatation was higher in tumors with nodal
metastasis, and also higher in poorly differentiated tumors. In stromal area of
OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor
associated endothelial cells was destroyed by these collagenases. CONCLUSION: In
the primary tumors with nodal metastasis, especially in poorly differentiated
OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1
and MMP-10 are important in the lysis of the glycocalyx inside the tumor
associated lymphatic endothelial cells.
PMID- 27489818
TI - Bone Healing Properties of Autoclaved Autogenous Bone Grafts Incorporating
Recombinant Human Bone Morphogenetic Protein-2 and Comparison of Two Delivery
Systems in a Segmental Rabbit Radius Defect.
AB - PURPOSE: This study aims to validate the effect of autoclaved autogenous bone
(AAB), incorporating Escherichia coli-derived recombinant human bone
morphogenetic protein-2 (ErhBMP-2), on critical-sized, segmental radius defects
in rabbits. Delivery systems using absorbable collagen sponge (ACS) and fibrin
glue (FG) were also evaluated. METHODS: Radius defects were made in 12 New
Zealand white rabbits. After autoclaving, the resected bone was reinserted and
fixed. The animals were classified into three groups: only AAB reinserted (group
1, control), and AAB and ErhBMP-2 inserted using an ACS (group 2) or FG (group 3)
as a carrier. Animals were sacrificed six or 12 weeks after surgery. Specimens
were evaluated using radiology and histology. RESULTS: Micro-computed tomography
images showed the best bony union in group 2 at six and 12 weeks after operation.
Quantitative analysis showed all indices except trabecular thickness were the
highest in group 2 and the lowest in group 1 at twelve weeks. Histologic results
showed the greatest bony union between AAB and radial bone at twelve weeks,
indicating the highest degree of engraftment. CONCLUSION: ErhBMP-2 increases bony
healing when applied on AAB graft sites. In addition, the ACS was reconfirmed as
a useful delivery system for ErhBMP-2.
PMID- 27489819
TI - Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy Studies on
Processed Tooth Graft Material by Vacuum-ultrasonic Acceleration.
AB - PURPOSE: The current gold standard for clinical jawbone formation involves
autogenous bone as a graft material. In addition, demineralized dentin can be an
effective graft material. Although demineralized dentin readily induces
heterotopic bone formation, conventional decalcification takes three to five
days, so, immediate bone grafting after extraction is impossible. This study
evaluated the effect of vacuum ultrasonic power on the demineralization and
processing of autogenous tooth material and documented the clinical results of
rapidly processed autogenous demineralized dentin (ADD) in an alveolar defects
patient. METHODS: The method involves the demineralization of extracted teeth
with detached soft tissues and pulp in 0.6 N HCl for 90 minutes using a heat
controlled vacuum-ultrasonic accelerator. The characteristics of processed teeth
were evaluated by scanning electron microscopy (SEM), and energy dispersive X-ray
spectroscopy (EDS). Bone grafting using ADD was performed for narrow ridges
augmentation in the mandibular area. RESULTS: The new processing method was
completed within two hours regardless of form (powder or block). EDS and SEM
uniformly demineralized autotooth biomaterial. After six months, bone remodeling
was observed in augmented sites and histological examination showed that ADD
particles were well united with new bone. No unusual complications were
encountered. CONCLUSION: This study demonstrates the possibility of preparing
autogenous tooth graft materials within two hours, allowing immediate one-day
grafting after extraction.
PMID- 27489820
TI - Powdered Wound Dressing Materials Made from wild Silkworm Antheraea pernyi Silk
Fibroin on Full-skin Thickness Burn Wounds on Rats.
AB - PURPOSE: This study evaluated powdered burn wound dressing materials from wild
silkworm fibroin in an animal model. METHODS: Fifteen rats were used in this
experiment. Full-thickness 2*2 cm burn wounds were created on the back of rats
under anesthesia. In the two experimental groups, the wounds were treated with
two different dressing materials made from silkworm fibroin. In the Control
Group, natural healing without any dressing material was set as control. The
wound surface area was measured at five days, seven days and 14 days. Wound
healing was evaluated by histologic analysis. RESULTS: By gross observation,
there were no infections or severe inflammations through 14 days post-injury. The
differences among groups were statistically significant at seven days and 14
days, postoperatively (P <0.037 and 0.001, respectively). By post hoc test, the
defect size was significantly smaller in experimental Group 1 compared with the
Control Group and experimental Group 2 at seven days postoperatively (P =0.022
and 0.029, respectively). The difference between Group 1 and Group 2 was
statistically significant at 14 days postoperatively (P <0.001). Group 1 and
control also differed significantly (P =0.002). Group 1 showed a smaller residual
scar than the Control Group and Group 2 at 14 days post-injury. Histologic
analysis showed more re-epithelization in Groups 1 and 2 than in the Control
Groups. CONCLUSION: Burn wound healing was accelerated with silk fibroin spun by
wild silkworm Antheraea pernyi. There was no atypical inflammation with silk
dressing materials. In conclusion, silk dressing materials can be used for
treatment of burn wound.
PMID- 27489821
TI - Risk Factors for Wound Dehiscence after Guided Bone Regeneration in Dental
Implant Surgery.
AB - PURPOSE: The purpose of this study was to evaluate risks for wound dehiscence
after guided bone regeneration (GBR) in dental implant surgery. METHODS: Patients
who received dental implant therapy with GBR procedure at Seoul National
University Bundang Hospital (Seongnam, Korea) from June 2004 to May 2007 were
included. The clinical outcome of interest was complications related to dental
implant surgery. The factors influencing wound dehiscence, classified into
patient-related factors, surgery-related factors and material-related factors,
were evaluated. RESULTS: One hundred and fifteen cases (202 implants) were
included in this study. Wound dehiscence (19.1%) was considered a major
complication. The risk of wound dehiscence was higher in males than in females
(odds ratio=4.279, P =0.014). In the main graft, the allogenic group had the
lowest risk of wound dehiscence (odds ratio=0.106, P =0.006). Though the external
connection group had a higher risk of wound dehiscence than the internal
connection group (odds ratio=2.381), the difference was not significant (P
=0.100). CONCLUSION: In this study, male gender and main graft have the highest
risk of wound dehiscence. To reduce wound dehiscence after GBR, instructions on
postoperative care with supplementary procedure for the protection of the wound
dehiscence is recommended, especially to male patients. A main graft with a gel
base can reduce the risk of wound dehiscence.
PMID- 27489822
TI - Horizontal Ridge Augmentation with Piezoelectric Hinge-Assisted Ridge Split
Technique in the Atrophic Posterior Mandible.
AB - Onlay bone grafting, guided bone regeneration, and alveolar ridge split technique
are considered reliable bone augmentation methods on the horizontally atrophic
alveolar ridge. Among these techniques, alveolar ridge split procedures are
technique-sensitive and difficult to perform in the posterior mandible. This case
report describes successful implant placement with the use of piezoelectric hinge
assisted ridge split technique in an atrophic posterior mandible.
PMID- 27489823
TI - Partial Necrosis of the Mandibular Proximal Segment Following Transoral Vertical
Ramus Osteotomy.
AB - Transoral vertical ramus osteotomy (TOVRO) procedure can result in a variety of
complications. Complications commonly reported include extensive bleeding due to
major blood vessel injury, unpredictable fracture, postoperative infection,
neurosensory deficit related Inferior alveolar nerve, insufficient
osteosynthesis, and temporomandibular joint problem. The authors describe a case
of partial necrosis of the mandibular proximal segment following TOVRO, a rarely
reported complication. A 37-year-old otherwise healthy woman underwent Lefort l
osteotomy and TOVRO to correct mandibular prognathism. Postoperatively, she
developed pain and swelling in the right submandibular region and was found to
have a partial necrosis of proximal segment.
PMID- 27489824
TI - Comparison of Costochondral Graft and Customized Total Joint Reconstruction for
Treatments of Temporomandibular Joint Replacement.
AB - PURPOSE: We review published research on temporomandibular joint (TMJ) total
replacement that compares costochondral graft and customized total joint
reconstruction (especially TMJ concepts), focusing on effectiveness. METHODS: We
searched PubMed databases, including prospective, retrospective, case-control or
longitudinal studies and significant statistical analysis. In data analysis, we
divided outcomes into 'Acceptable' or 'Non-acceptable'. RESULTS: There were seven
articles found dealing with costochondral graft and 180 patients. The majority of
patients had satisfactory treatment outcomes (n=109, 61%). There were six
articles including 275 patients using the alloplastic material TMJ concepts.
Almost all patients had satisfactory treatment outcomes (n=261, 95%). CONCLUSION:
Comparing customized total joint reconstruction with costochondral graft, use of
TMJ concepts resulted in increased quality of life and fewer complications. In
conclusion, we judged that alloplastic material such as TMJ concepts is more
effective device in total joint replacement than costochondral graft.
PMID- 27489825
TI - Facial Bone Fracture Patients Visiting Pusan National University Hospital in
Busan and Yangsan: Trends and Risks.
AB - PURPOSE: This study examined patients with facial bone fracture visiting Pusan
National University Dental Hospital to understand the trends, and to enhance
appropriate care and treatment for patients with facial bone fracture. METHODS:
We investigated 531 patients presenting with facial bone fracture in Yangsan and
802 patients in Busan from January 2010 to December 2013. We divided the patients
by year, month, gender, age, site, and cause to compare with historic data and
other studies. RESULTS: The gender ratio was 3.58:1 in Yangsan and 4.31:1 in
Busan. Patients aged in their 20s had the highest number of facial bone fractures
in both Yangsan and Busan. The most frequent fracture site was the mandible, and
the most frequent cause was slip down in both Yangsan and Busan. CONCLUSION: The
investigation and comparison of patients with facial bone fracture who visited
Pusan National University Hospital located at Yangsan and Busan from 2010 to 2013
found a difference in the total number of patients at each hospital, but the
trends were not significantly different.
PMID- 27489826
TI - The Efficacy of the Graft Materials after Sinus Elevation: Retrospective
Comparative Study Using Panoramic Radiography.
AB - PURPOSE: This study compares and evaluates the efficacy of graft materials after
maxillary sinus bone grafts with autogenous tooth bone graft material (AutoBT),
demineralized freeze-dried bone allograft (DFDBA) and deproteinized bovine bone
mineral (DBBM). METHODS: The study involved 30 sinuses in 26 patients who visited
the Division of Oral and Maxillofacial Surgery, Department of Dentistry in Ajou
University Hospital and received either AutoBT, DFDBA or DBBM with sinus
elevation using the lateral window technique. Sinus graft height was measured
before, immediately after, and six months after bone graft with panoramic
radiography and the height changes of the sinus floor was compared according to
the graft materials. RESULTS: After six months, the decrease ratio of graft
heights were 13.57% for AutoBT group, 14.30% for DFDBA group, and 11.92% for DBBM
group. There was no statistically significant difference. CONCLUSION: The new
maxillary sinus floor formed by the upper border of bone graft material, can
repneumatize after the maxillary sinus elevation. Thus, long-term stability of
sinus graft height represents an important factor for implant success. We found
that the three graft materials for sinus elevation do not differ significantly
and all three graft materials showed excellent resistance to maxillary sinus
repneumatization. However, due to the special circumstances of the maxillary
sinus and small sample, the actual difference between the three graft materials
may not have been detectable. Therefore further study needs to be conducted for
more reliable study results.
PMID- 27489827
TI - Anchor Plate Efficiency in Postoperative Orthodontic Treatment Following
Orthognathic Surgery via Minimal Presurgical Orthodontic Treatment.
AB - PURPOSE: The efficiency of an anchor plate placed during orthognathic surgery via
minimal presurgical orthodontic treatment was evaluated by analyzing the
mandibular relapse rate and dental changes. METHODS: The subjects included nine
patients with Class III malocclusion who had bilateral sagittal split osteotomy
at the Division of Oral and Maxillofacial Surgery, Department of Dentistry in
Ajou University Hospital, after minimal presurgical orthodontic treatment. During
orthognathic surgery, anchor plates were placed at both maxillary buttresses. The
anchor plates were used to move maxillary teeth backward and for maximum
anchorage of Class III elastics to minimize mandibular relapse during the
postoperative orthodontic treatment. The lateral cephalometric X-ray was taken
preoperatively (T0), postoperatively (T1), and one year after the surgery (T2).
Seven measurements (distance from Pogonion to line Nasion-Nasion perpendicular
[Pog-N Per.], angle of line B point-Nasion and Nasion-Sella [SNB], angle of line
maxilla 1 root-maxilla 1 crown and Nasion-Sella [U1 to SN], distance from maxilla
1 crown to line A point-Nasion [U1 to NA], overbite, overjet, and interincisal
angle) were taken. Measurements at T0 to T1 and T1 to T2 were compared and
differences tested by standard statistical methods. RESULTS: The mean skeletal
change was posterior movement by 13.87+/-4.95 mm based on pogonion from T0 to T1,
and anterior movement by 1.54+/-2.18 mm from T1 to T2, showing relapse of about
10.2%. There were significant changes from T0 to T1 for both Pog-N Per. and SNB
(P <0.05). However, there were no statistically significant changes from T1 to T2
for both Pog-N Per. and SNB. U1 to NA that represents the anterior-posterior
changes of maxillary incisor did not differ from T0 to T1, yet there was a
significant change from T1 to T2 (P <0.05). CONCLUSION: This study found that the
anchor plate minimizes mandibular relapse and moves the maxillary teeth backward
during the postoperative orthodontic treatment. Thus, we conclude that the anchor
plate is clinically very useful.
PMID- 27489828
TI - Considerations and Protocols in Virtual Surgical Planning of Reconstructive
Surgery for More Accurate and Esthetic Neomandible with Deep Circumflex Iliac
Artery Free Flap.
AB - PURPOSE: The reconstruction of mandibular defects poses many difficulties due to
the unique, complex shape of the mandible and the temporomandibular joints. With
development of microvascular anastomosis, free tissue transplantation techniques,
such as deep circumflex iliac artery (DCIA) flap and fibular free flap (FFF),
were developed. The DCIA offers good quality and quantity of bone tissue for
mandibular segmental defect and implant for dental rehabilitation. Virtual
surgical planning (VSP) and stereolithography-guided osteotomy are currently
successfully applied in three-dimensional mandibular reconstruction, but most use
FFF. There are only a few articles on reconstruction with the DCIA that assess
the postoperative results. METHODS: Three patients admitted during a five month
period (April of 2013 to August of 2013) underwent resection of mandible and DCIA
musculo-osseous reconstruction using a VSP and stereolithographic modeling and
assessment of outcomes included technical accuracy, esthetic contour, and
functional outcomes. RESULTS: This technique yielded iliac bone segment with
excellent apposition and duplication of the preoperative plan. Flap survival was
100 percent and all patients maintained preoperative occlusion and contour.
CONCLUSION: Based on our experience, we offer considerations and logically
consistent protocols by classification of mandibular defects, and demonstrate the
benefits in VSP and stereolithographic modeling of mandibular reconstructive
surgery with DCIA flap.
PMID- 27489829
TI - Trismus Due to Bilateral Coronoid Hyperplasia.
AB - Bilateral coronoid hyperplasia causes painless progressive trismus, resulting
from coronoid process impingement on the posterior aspect of the zygomatic bone.
The etiology of coronoid hyperplasia is unclear, with various theories proposed.
An endocrine stimulus, increased temporalis activity, trauma, genetic inheritance
and familial occurrence have all been proposed, but no substantive evidence
exists to support any of these hypotheses. Multiplanar reformatting of axial
scans and 3-dimensional reconstruction permit precise reproduction of the shape
and size of the coronoid and malar structures, and relationships of all
structures of the temporal and infratemporal fossae. This case shows remarkably
increased mouth opening by coronoidectomy in a patient who complained of trismus
due to hyperplasia of coronoid process.
PMID- 27489830
TI - Extensive Adenomatoid Odontogenic Tumor of the Maxilla: A Case Report of
Conservative Surgical Excision and Orthodontic Alignment of Impacted Canine.
AB - The present report describe the surgical therapy, clinical course, orthodontic
treatment and morphological characteristics of an adenomatoid odontogenic tumor
in the maxilla of an 11-year-old patient. The cystic tumor filled the maxillary
sinus and involved a tooth. Marsupialization was accompanied by partial
enucleation and applied traction to the affected tooth by a fixed orthodontic
appliance. Healing was uneventful and no local recurrence was observed during a 1
year period of follow-up control.
PMID- 27489831
TI - Correction of Lip Canting Using Bioabsorbables during Orthognathic Surgery.
AB - Lip canting is associated with facial asymmetry, and is one of the most
challenging problems in surgical correction of facial deformities. The author
corrected lip canting using bioabsorbable devices during orthognathic surgery.
Soft tissue suspension procedures were performed on four patients with facial
asymmetry. Lip lines improved for all patients. Over an observation period of
five years, no complications were noted, nor did any late relapse develop.
Furthermore, as time past, the effect of the Endotine suspension procedure
increased probably due to induction of fibrosis on surrounding soft tissues.
PMID- 27489832
TI - Changes of the Airway Space and the Position of Hyoid Bone after Mandibular Set
Back Surgery Using Bilateral Sagittal Split Ramus Osteotomy Technique.
AB - PURPOSE: Although there have been several studies of reduced airway space after
mandibular setback surgery using the sagittal split ramus osteotomy technique,
research on the risk factors for changes of the airway space is lacking.
Therefore, this study was performed to examine airway changes and the position of
the hyoid bone after orthognathic surgery, and to assess possible risk factors.
METHODS: In this retrospective study, 50 patients who underwent posterior
displacement of the mandible by the bilateral sagittal split ramus osteotomy
technique were included. Changes of the position of the hyoid bone and the airway
space were analyzed over various follow-up periods, using cephalometric
radiography taken preoperatively, immediately after surgery, eight weeks after
surgery, six months after surgery, and one year after surgery. To identify risk
factors, multiple regression analysis of age, gender, body mass index (BMI),
posterior mandibular movement, and the presence of genioplasty was performed.
RESULTS: Inferor and posterior movement of the hyoid bone was observed
postoperatively, but subsequent observations showed regression towards the
anterosuperior aspect. The airway space also significantly decreased after
surgery (P <0.05), and increased slightly up until six months after surgery. The
airway space significantly decreased (beta=0.47, P <0.01) as the amount of
mandibular setback increased. However, age, sex, BMI, and presence of genioplasty
were not associated with airway reduction. CONCLUSION: The amount of mandibular
set back was significantly associated with postoperative reduction of airway
space. It is necessary to establish a treatment plan considering this factor.
PMID- 27489834
TI - A Clinical Study of Mandibular Angle Fracture.
AB - PURPOSE: To establish management protocol for mandibular angle fracture, we
describe pertinent factors including cause, impacted third molar and recent
treatment tendency. METHODS: We examined the records of 62 patients who had
unilateral mandibular angle fracture. Sixty patients who had open reduction
surgery were examined at postoperative weeks 1, 4, 8, 12, and 28. RESULTS: Left
mandibular angle fracture is frequent in younger males. Presence of the
mandibular third molar can increase fracture risk. Because of attached muscle,
favorable fractures occurred primarily in the mandibular angle area. CONCLUSION:
Extracting the mandibular third molar can prevent angle fractures, and open
reduction with only one plate adaptation is generally the proper treatment method
for mandibular angle fracture.
PMID- 27489833
TI - Soft Tissue Augmentation with Silk Composite Graft.
AB - PURPOSE: The objective of this study was to evaluate the interaction between 4
hexylresorcinol (4HR) and antibody as that affects the performance of a silk-4HR
combination graft for soft tissue augmentation in an animal model. METHODS: The
silk graft materials consisted of four types: silk+10% tricalcium phosphate (TCP)
(ST0), silk+10% TCP+1% 4HR (ST1), silk+10% TCP+3% 4HR (ST3), and silk+10% TCP+6%
4-HR (ST6). The antibody binding assay tested the 4HR effect and scanning
electron microscopic (SEM) exam was done for silk grafts. The animal experiment
used a subcutaneous pocket mouse model. The graft - SH0 or SH1 or SH3 or SH6 -
was placed in a subcutaneous pocket. The animals were killed at one, two, and
four weeks, postoperatively. The specimens were subjected to histological
analysis and lysozyme assay. RESULTS: Groups with 4HR applied showed lower
antibody binding affinity to antigen compared to groups without 4HR. In the SEM
examination, there was no significant difference among groups. Histological
examinations revealed many foreign body giant cells in ST0 and ST1 group at four
weeks postoperatively. Both ST3 and ST6 groups developed significantly lower
levels of giant cell values compared to ST0 and ST1 groups (P <0.001) at four
weeks postoperatively. In the lysozyme assay, the ST1 and ST3 groups showed
denser signals than the other groups. CONCLUSION: 4HR combined silk implants
resulted in high levels of vascular and connective tissue regeneration.
PMID- 27489835
TI - Surgical Management of Edentulous Atrophic Mandible Fractures in the Elderly.
AB - Fractures of the mandible occur with a greater frequency in the elderly. This
study reports three cases of edentulous atrophic mandible fracture in elderly
patients treated with open reduction technique. Three patients who presented with
edentulous atrophic mandible fractures underwent surgical management using open
reduction and internal fixation. After treatment, clinical evaluations and
postoperative complications were examined with postoperative x-ray. Patients were
followed with clinical and radiographic examinations. In the postoperative
clinical evaluation, two male patients healed well, but one female patient
complained of pain and swelling. In radiographic examinations, no union delay or
lack of fusion was observed in the edentulous area. Open reduction technique is a
viable treatment option for the edentulous atrophic mandible fractures in
geriatric patients.
PMID- 27489836
TI - Simultaneous Glossectomy with Orthognathic Surgery for Mandibular Prognathism.
AB - Macroglossia can create dental and skeletal instability after orthodontic
treatment or orthognathic surgery for mandibular prognathism. In relevant
literature, partial glossectomy is suggested for a good post-treatment prognosis.
Most of the published partial glossectomy cases are two-staged surgery, because
of concern about postoperative airway obstruction. As orthognathic surgical
techniques and fixation method develop, however, concerns about postoperative
airway obstruction have lessened. In this case, mandibular setback surgery and
partial glossectomy were performed simultaneously, leading to stable recovery
without any postoperative respiratory problems. After surgical technique to
preserve the tongue tip, we achieved good outcomes without postoperative side
effects of lingual hypoesthesia, pronunciation disorder and dyskinesia. We report
this case with a literature review.
PMID- 27489837
TI - Successful Localization of Intraoral Foreign Body with C-arm Fluoroscopy.
AB - During surgical procedures, unexpected material, including surgical instruments
and tissue segments, may get lost in the surgical field. Most of these should be
immediately removed to prevent further complications, such as vital organ
irritation, infection, and inflammatory pseudo-tumor formation. However, it is
not always easy to define the exact location of the foreign body, especially if
the item is very small and/or it is embedded in the soft tissue of the head and
neck region. Intraoperative real-time radiological imaging with C-arm fluoroscopy
can be useful to trace the three-dimensional location of small and embedded
foreign bodies in the oral and maxillofacial area. We describe an unusual case of
an embedded micro-screw in the intrinsic tongue muscle that had been dropped into
the sublingual space during a lower alveolar bone graft procedure. The lost
foreign body was accurately identified with C-arm fluoroscopy and safely removed
without any further complications.
PMID- 27489838
TI - Vertical Augmentation of Maxillary Posterior Alveolar Ridge Using Allogenic Block
Bone Graft and Simultaneous Maxillary Sinus Graft.
AB - The maxillary posterior area is the most challenging site for the dental implant.
Although the sinus graft is a predictable and successful technique for
rehabilitation of atrophic and pneumatized posterior maxilla, when there is
severe destruction of alveolar bone, a very long crown length remains challenging
after successful dental implants installation with sinus graft. We performed
vertical augmentation of the maxillary posterior alveolar ridge using the
allogenic block bone graft with a simultaneous sinus graft using allogenic and
heterogenic bone chips. After about six months, we installed the dental implant.
After this procedure, we achieved a more favorable crown-implant fixture ratio
and better results clinically and biomechanically. This is a preliminary report
of vertical augmentation of maxillary posterior alveolar ridge using allogenic
block bone graft and simultaneous maxillary sinus graft. Further research
requires longer observation and more patients.
PMID- 27489839
TI - Corrective Rhinoplasty with Combined Use of Autogenous Auricular Cartilage and
Porcine Dermal Collagen in Cleft Lip Nose Deformity.
AB - Esthetic reconstruction of cleft lip nose deformity is a challenging task in
surgical management of patients with orofacial cleft. The author reconstructed
cleft lip nose deformity effectively using autogenous auricular cartilage and a
relatively new graft material of porcine dermal collagen, PermacolTM. After
correction of the deformed lower third of the nose with patient's auricular
cartilage, we applied PermacolTM to augment the entire nasal dorsum. Three
patients were treated and followed for up to five years. All patients improved in
nose aesthetics without any inflammatory or immunogenic reaction. The author
suggests that the use of PermacolTM for nasal profile augmentation in the
treatment of cleft lip nose deformity is an alternative surgical strategy with
minimal surgical invasiveness. The author report long-term experience with
combined use of auricular cartilage and PermacolTM in nasal reconstruction for
cleft lip nose deformity.
PMID- 27489840
TI - Correction: Trismus Due to Bilateral Coronoid Hyperplasia.
AB - [This corrects the article on p. 168 in vol. 36.].
PMID- 27489841
TI - Membranes for the Guided Bone Regeneration.
AB - Many kinds of membrane have been used for the guided bone regeneration (GBR)
technique. However, most membranes do not fulfill all requirements for the ideal
membrane for the GBR technique. Among them, collagen membrane has been most
widely used. However, its high price and weak tensile strength in wet condition
are limitations for wide clinical application. Synthetic polymers have also been
used for the GBR technique. Recently, silk based membrane has been considered as
a membrane for the GBR technique. Despite many promising preclinical data for use
of a silk membrane, clinical data regarding the silk membrane has been limited.
However, silk based material has been used clinically as vessel-tie material and
an electrospun silk membrane was applied successfully to patients. No adverse
effect related to the silk suture has been reported. Considering that silk
membrane can be provided to patients at a cheap price, its clinical application
should be encouraged.
PMID- 27489842
TI - Comparative Study of the Early Loading of Resorbable Blasting Media and
Sandblasting with Large-grit and Acid-etching Surface Implants: A Retrospective
Cohort Study.
AB - PURPOSE: This study compares the prognosis (the survival rate and marginal bone
loss) of resorbable blasting media (RBM) surface implants and sandblasting with
large-grit and acid-etching (SLA) surface implants in the early loading. METHODS:
This study targeted 123 patients treated by implants installation from January
2008 to March 2010. The loading was initiated in the maxilla within three to four
months and in the mandible within one to two months. The types of restoration
were single crown and fixed partial prosthesis. Those functioned over one year.
The implants were classified by the surface of implants as Group 1: RBM surface
(GS III; OSSTEM, Busan, Korea) and, Group 2: SLA surface (Superline; Dentium,
Seoul, Korea). The groups were categorized by maxilla and mandible and compared
by survival rate, marginal bone loss through clinical records evaluation, and
radiographic measurements. RESULTS: The marginal bone loss in the maxilla was
0.14+/-0.34 mm (Group 1) and 0.30+/-0.37 mm (Group 2), a statistically
significant difference (P <0.05). In the mandible those were 0.28+/-0.54 mm
(Group 1) and 0.20+/-0.33 mm (Group 2), not significant (P >0.05). There was no
significant difference of marginal bone loss between maxilla and mandible by
groups. During observation there was no implant failure, a survival rate of 100%.
CONCLUSION: Both surfaces showed an excellent survival rate, and the marginal
bone loss was not substantial.
PMID- 27489843
TI - Maxillofacial Trauma Trends at a Tertiary Care Hospital: A Retrospective Study.
AB - PURPOSE: Maxillofacial fractures are rapidly increasing from car accidents,
industrial accidents, teenaged criminal activity, and sports injuries. Accurate
assessment, appropriate diagnosis, and preparing individual treatment plans are
necessary to reduce surgical complications. We investigated recent trends of
facial bone fracture by period, cause, and type, with the objective of reducing
surgical complications. METHODS: To investigate time trends of maxillofacial
fractures, we reviewed medical records from 2,196 patients with maxillofacial
fractures in 1981~1987 (Group A), 1995~1999 (Group B), and 2008~2012 (Group C).
We analyzed each group, comparing the number of patients, sex ratio, age,
fracture site, and etiology. RESULTS: The number of patients in each period was
418, 516, and 1,262 in Groups A to C. Of note is the increase in the number of
patients from Group A to C. The sex ratios were 5.6:1, 3.5:1, and 3.8:1 in Groups
A, B, and C. The most affected age group for fracture is 20~29 in all three
groups. Traffic accidents are the most common cause in Groups A and B, while
there were somewhat different causes of fracture in Group C. Sports-induced
facial trauma was twice as high in Group C compared with Group A and B. Mandible
fracture accounts for a large portion of facial bone fractures overall.
CONCLUSION: We observed an increase in facial bone fracture patients at Kyungpook
National University Dental Hospital over the years. Although facial injury caused
by traffic accidents was still a major cause of facial bone fracture in all
periods, the percentage decreased. In recent years, isolated mandible fracture
increased but mandible and mid-facial complex fracture decreased, possibly
because of a reduction in traffic accidents.
PMID- 27489844
TI - Anatomical and Functional Recovery of Intracapsular Fractures of the Mandibular
Condyle: Analysis of 124 Cases after Closed Treatment.
AB - PURPOSE: The purpose of this study is to evaluate the influence of intracapsular
fracture lines of the mandibular condyle on the anatomical and functional
recovery after non-surgical closed treatment. METHODS: Clinical and radiological
follow-up of 124 patients with intracapsular fractures of the mandibular condyle
was performed after closed treatment between 2005 and 2012. The intracapsular
fractures were classified into three categories: type A (medial condylar pole
fracture), type B (lateral condylar pole fracture with loss of vertical height)
and type M (multiple fragments or comminuted fracture). RESULTS: By radiological
finding, fracture types B and M lost up to 24% vertical height of the mandibular
condyle compared to the height on the opposite side. In Type M, moderate to
severe dysfunction was observed in 33% of the cases. Bilateral fractures were
significantly associated with the risk of temporomandibular joint (TMJ)
dysfunction in fracture types A and B. Bilateral fracture and TMJ dysfunction
were not statistically significantly associated in type M fractures. CONCLUSION:
Most of the mandibular intracapsular condylar fractures recovered acceptably
after conservative non-surgical treatment with functional rehabilitation, even
with some anatomical shortening of the condylar height. The poor functional
recovery encountered in type M fractures, especially in cases with additional
fracture sites and bilateral fractures, points up the limitation of closed
treatment in such cases.
PMID- 27489845
TI - The Retrospective Study of Closed Reduction of Nasal Bone Fracture.
AB - PURPOSE: This study was conducted in order to investigate the therapeutic effect
of closed reduction according to a classification in patients with nasal bone
fracture. METHODS: The study was conducted retrospectively on 186 patients with a
mean age of 38 years (range: 7 to 80 years). All patients were diagnosed by
clinical and radiologic examination, and then classified according to Hwang's
classification by computed tomography. The patients were further classified by
their age, gender, causes of fracture, operation timing after fracture,
concurrent facial bone fracture, and complications. All patients underwent the
same reduction and treatment protocol and were then followed up regularly for at
least three months. RESULTS: The cause of the fracture was slip down, and the
highest prevalence was shown in the 20s. The mean operation timing after fracture
was 4.1 days (range: 1 to 14 days), and it tended to be longer in the case of
defected septal bone or more severe fracture. The most common concurrent facial
bone fracture was orbital blow-out fracture, and zygomaticomaxillary complex and
maxillary fracture occured frequently. The largest number of complications
occurred in class III and IIBs patients, and the main complication was
postoperative pain. CONCLUSION: Results of nasal bone closed reduction on the 186
patients showed that serious complications rarely occurred. Closed reduction is
generally an effective treatment for nasal bone fracture. However, in the case of
severe concurrent septal bone fracture or comminuted fracture with depression,
open reduction should be considered. Further study with a larger number of
patients and further classification is required.
PMID- 27489846
TI - Effectiveness of Computed Tomography for Blow-out Fracture.
AB - PURPOSE: This study assessed the association between eye symptoms (enophthalmos
or diplopia) and site of damage, volume, deviated inferior rectus muscle (IRM)
and type of fracture with computed tomography (CT). The intent is to anticipate
the prognosis of orbital trauma at initial diagnosis. METHODS: Forty-five
patients were diagnosed with fractures of the inferior wall of one orbit.
Fracture area, volume of displaced tissue, deviated IRM, and type of fracture
were evaluated from coronal CT by one investigator. The association of those
variables with the occurrence of eye symptoms (diplopia and enophthalmos) was
assessed. RESULTS: Of 45 patients, 27 were symptom-free (Group A) and 18 had
symptoms (Group B) of enophthalmos and/or diplopia. In Group B, 12 had diplopia,
one was enophthalmos, and five had both. By CT measurement, group A mean area was
192.6 mm(2) and the mean volume was 673.2 mm(3). Group B area was 316.2 mm(2) and
volume was 1,710.6 mm(3). The volume was more influential on symptom occurrence.
Each patient was categorized into four grades depending on the location of IRM.
Symptom occurrence and higher grade were associated. Twenty-six patients had trap
door fracture (one side, attached to the fracture), and 19 had punched-out
fracture (both sides detached). The punched-out fracture was more strongly
associated with symptoms and had statistically significantly higher area and
volume. CONCLUSION: In orbital trauma, measurement of fracture area and volume,
evaluation of the deviated IRM and classification of the fracture type by coronal
CT can effectively predict prognosis and surgical indication.
PMID- 27489847
TI - Effectiveness of Woven Silk Dressing Materials on Full-skin Thickness Burn Wounds
in Rat Model.
AB - PURPOSE: This study evaluated woven silk textile for burn wound dressing
materials in an animal model. METHODS: Ten rats were used in this experiment.
Full-thickness 2*2 cm burn wounds were created on the back of the rats under
anesthesia. In the experimental group, the wounds were treated with three
different dressing materials from woven silk textile. In the control group,
natural healing without any dressing material was set as control. The wound
surface area was measured at five days, seven days, and 14 days. Wound healing
was evaluated by histologic analysis. RESULTS: There were no statistically
significant differences among groups at five days post injury. The mean defect
size at seven days was largest in Group 3 (462.87 mm(2)), and smallest in Group 1
(410.89 mm(2)), not a significant difference (P =0.341). The mean defect size at
14 days was smallest at the Group 3 (308.28 mm(2)) and largest in the control
group (388.18 mm(2)), not a significant difference (P =0.190). The denuded area
was smaller in Group 1 (84.57 mm(2)) and Group 2 (82.50 mm(2)) compared with the
control group (195.93 mm(2)), not statistically significant differences (P
=0.066, 0.062). The difference between Group 3 and control was also not
statistically significant (P =0.136). In histologic analysis, the experimental
groups re-epithelialized more than control groups. No evidence was found of
severe inflammation. CONCLUSION: The healing of burn wounds was faster with silk
weave textile more than the control group. There was no atypical inflammation
with silk dressing materials. In conclusion, silk dressing materials could be
used to treat burn wounds.
PMID- 27489848
TI - Osteomyelitis in an Osteopathia Striata with Cranial Sclerosis Patient.
AB - Osteopathia striata with cranial sclerosis (OS-CS) is characterized by linear
bone dysplasia at the long bone radiographically and sclerotic change at the
cranium. The purpose of this case report is to study the symptoms and treatments
of osteomyelitis in a patient with OS-CS. A 41-year-old patient had pus discharge
from a fistula at the mental region and increase in radiolucencies with sequestra
in panoramic radiograph images. Computed tomography (CT) as well as radiograph
images for the whole skeleton were taken. The patient was diagnosed with OS-CS.
Sequestrectomy and fistulectomy were performed. The patient recovered and no
relapse occurred within six months after surgery. For diagnosis of OS-CS, CT and
additional radiograph images for the whole skeleton are required. Because of the
increased bone density, this patient is prone to relapse after sequestrectomy.
Therefore, the surgeon must minimize trauma with the least incision and
exfoliation, and preoperative antibiotics.
PMID- 27489849
TI - Nevoid Basal Cell Carcinoma Syndrome: A Case Report and Review of Korean Cases.
AB - Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal genetic disease
caused by a PTCH mutation. The disease is characterized by multiple basal cell
carcinomas of the skin, multiple keratocystic odontogenic tumors (KCOTs) in the
jaw, palmar and/or plantar pits, bifid ribs, ectopic calcification of the falx
cerebri, and skeletal abnormalities. Early diagnosis is difficult in many cases
because there may be a number of systemic symptoms. The purpose of this study is
to report the case of a 12-year-old girl who was hospitalized with multiple KCOTs
that occurred in the upper and lower jaws. Through characteristic clinical
symptoms and radiologic findings, she was finally diagnosed as having NBCCS. This
study also aims to organize the symptoms often observed in Korea using previously
published case reports to provide useful information for the early diagnosis of
NBCCS.
PMID- 27489850
TI - Defatting Vestibuloplasty for Functional and Esthetic Reconstruction of Tongue.
AB - The radial forearm free flap (RFFF) is a thin and pliable tissue with many
advantages for tongue reconstruction. However, tongues reconstructed with RFFF
occasionally need revision surgery because inadequate defect measurement at
primary surgery can lead to bulkiness and limited movement of reconstructed
tongue. In this case, the patient underwent partial glossectomy and RFFF
reconstruction for treatment of tongue cancer five years prior. We could not make
a lower denture for the patient, because the alveolo-lingual sulcus of tongue was
almost lost. So we performed vestibuloplasty with a modified Kazanjian method on
the lingual vestibule of the mandibular right posterior area, and defatting
surgery to debulk the flap. After surgery, we observed that the color and texture
of the revised tongue changed to become similar with adjacent tissue. The patient
obtained a more functional and esthetic outcome. Accordingly, we present a case
report with a review of relevant literature.
PMID- 27489851
TI - Undifferentiated Pleomorphic Sarcoma in Mandible.
AB - Undifferentiated pleomorphic sarcoma (UPS), previously known as malignant fibrous
histiocytoma, occurs commonly in the soft tissues in adult, but is rare in the
maxillofacial region. It consists of undifferentiated mesenchymal tumor cells
resembling histiocytes and fibroblasts. The purpose of this article is to report
a case of UPS in the mandible. A 44-year-old patient presented with a painful
growing mass in the mandible of two months' duration. Computed tomography and
positron emission tomography-computed tomography revealed an ill-defined
heterogenous, hypermetabolic mass about 4 cm in size in the left mandible
invading adjacent soft tissues. A left mandiblulectomy and reconstruction with a
fibular free flap were performed. Immunohistochemical study gave a diagnosis of
UPS. The patient was referred for adjuvant chemotherapy after surgical removal of
the tumor.
PMID- 27489852
TI - Decompression Device Using a Stainless Steel Tube and Wire for Treatment of
Odontogenic Cystic Lesions: A Technical Report.
AB - Decompression is considered an effective treatment for odontogenic cystic lesions
in the jaw. A variety of decompression devices are successfully used for the
treatment of keratocystic odontogenic tumors, radicular cysts, dentigerous cysts,
and ameloblastoma. The purpose of these devices is to keep an opening between the
cystic lesion and the oral environment during treatment. The aim of this report
is to describe an effective decompression tube using a stainless steel tube and
wire for treatment of jaw cystic lesions.
PMID- 27489853
TI - Psychosocial Outcomes of Sharing a Diagnosis of Cancer with a Pediatric Patient.
AB - PURPOSE: This innovative pilot study was designed to provide research-based
evidence on the variables to consider informing a child of his/her cancer
diagnosis, so as to minimize the negative psychosocial effects of the cancer
experience on survivors. The hypotheses of the study were that "good information"
about cancer, will allow the child a better understanding way to cope with
treatment and improve sociopsychological outcomes at adulthood. METHODS: Ninety
one adult childhood cancer (CC) survivors got the questionnaires while waiting to
their routine checkup at a grate CC medical center in center Israel. RESULTS: To
our surprise and not according to the hypothesis, there was a difference between
children diagnosed up to 12 years of age and those diagnosed during adolescence.
(Participants were divided into two groups according to their age at diagnosis:
from birth to 12 years old and from age 12-18). In the group diagnosed at a
younger age, those who had received "good information" were found to have better
quality of life, lower mental pain, and higher mental pain tolerance than did
those in the same group (diagnosed at a younger age) who received "not good
information." By contrast, in the group diagnosed during adolescence, those who
had received "not good information" scored higher on these measures than did
their counterparts who had received "good information." CONCLUSION: Given that
information conveyed to children diagnosed with cancer can have a significant
impact on survivors' quality of life, further research is needed to determine the
precise information to be divulged to children at the time of diagnosis. In the
meantime, extreme caution, sensitivity, and careful judgment are required.
CLINICAL RELEVANCE: Findings of the current study and of future studies can be
used to formulate clear guidelines for assessing a child's readiness and the
information to be divulged, so as to improve the quality of life of CC survivors.
PMID- 27489854
TI - Nanochemistry of Protein-Based Delivery Agents.
AB - The past decade has seen an increased interest in the conversion of food proteins
into functional biomaterials, including their use for loading and delivery of
physiologically active compounds such as nutraceuticals and pharmaceuticals.
Proteins possess a competitive advantage over other platforms for the development
of nanodelivery systems since they are biocompatible, amphipathic, and widely
available. Proteins also have unique molecular structures and diverse functional
groups that can be selectively modified to alter encapsulation and release
properties. A number of physical and chemical methods have been used for
preparing protein nanoformulations, each based on different underlying protein
chemistry. This review focuses on the chemistry of the reorganization and/or
modification of proteins into functional nanostructures for delivery, from the
perspective of their preparation, functionality, stability and physiological
behavior.
PMID- 27489855
TI - Role of Cysteine Residues in the Carboxyl-Terminus of the Follicle-Stimulating
Hormone Receptor in Intracellular Traffic and Postendocytic Processing.
AB - Posttranslational modifications occurring during the biosynthesis of G protein
coupled receptors include glycosylation and palmitoylation at conserved cysteine
residues located in the carboxyl-terminus of the receptor. In a number of these
receptors, these modifications play an important role in receptor function and
particularly, in intracellular trafficking. In the present study, the three
cysteine residues present in the carboxyl-terminus of the human FSHR were
replaced with glycine by site-directed mutagenesis. Wild-type and mutant
(Cys627/629/655Gly) FSHRs were then transiently expressed in HEK-293 cells and
analyzed for cell-surface plasma membrane expression, agonist-stimulated
signaling and internalization, and postendocytic processing in the absence and
presence of lysosome and/or proteasome inhibitors. Compared with the wild-type
FSHR, the triple mutant FSHR exhibited ~70% reduction in plasma membrane
expression as well as a profound attenuation in agonist-stimulated cAMP
production and ERK1/2 phosphorylation. Incubation of HEK-293 cells expressing the
wild-type FSHR with 2-bromopalmitate (palmitoylation inhibitor) for 6 h,
decreased plasma membrane expression of the receptor by ~30%. The internalization
kinetics and beta-arrestin 1 and 2 recruitment were similar between the wild-type
and triple mutant FSHR as disclosed by assays performed in non-equilibrium
binding conditions and by confocal microscopy. Cells expressing the mutant FSHR
recycled the internalized FSHR back to the plasma membrane less efficiently than
those expressing the wild-type FSHR, an effect that was counteracted by
proteasome but not by lysosome inhibition. These results indicate that
replacement of the cysteine residues present in the carboxyl-terminus of the
FSHR, impairs receptor trafficking from the endoplasmic reticulum/Golgi apparatus
to the plasma membrane and its recycling from endosomes back to the cell surface
following agonist-induced internalization. Since in the FSHR these cysteine
residues are S-palmitoylated, the data presented emphasize on this
posttranslational modification as an important factor for both upward and
downward trafficking of this receptor.
PMID- 27489856
TI - The Verrucomicrobia LexA-Binding Motif: Insights into the Evolutionary Dynamics
of the SOS Response.
AB - The SOS response is the primary bacterial mechanism to address DNA damage,
coordinating multiple cellular processes that include DNA repair, cell division,
and translesion synthesis. In contrast to other regulatory systems, the
composition of the SOS genetic network and the binding motif of its
transcriptional repressor, LexA, have been shown to vary greatly across bacterial
clades, making it an ideal system to study the co-evolution of transcription
factors and their regulons. Leveraging comparative genomics approaches and prior
knowledge on the core SOS regulon, here we define the binding motif of the
Verrucomicrobia, a recently described phylum of emerging interest due to its
association with eukaryotic hosts. Site directed mutagenesis of the
Verrucomicrobium spinosum recA promoter confirms that LexA binds a 14 bp
palindromic motif with consensus sequence TGTTC-N4-GAACA. Computational analyses
suggest that recognition of this novel motif is determined primarily by changes
in base-contacting residues of the third alpha helix of the LexA helix-turn-helix
DNA binding motif. In conjunction with comparative genomics analysis of the LexA
regulon in the Verrucomicrobia phylum, electrophoretic shift assays reveal that
LexA binds to operators in the promoter region of DNA repair genes and a
mutagenesis cassette in this organism, and identify previously unreported
components of the SOS response. The identification of tandem LexA-binding sites
generating instances of other LexA-binding motifs in the lexA gene promoter of
Verrucomicrobia species leads us to postulate a novel mechanism for LexA-binding
motif evolution. This model, based on gene duplication, successfully addresses
outstanding questions in the intricate co-evolution of the LexA protein, its
binding motif and the regulatory network it controls.
PMID- 27489857
TI - Elevated Linoleic Acid (A Pro-Inflammatory PUFA) and Liver Injury in a Treatment
Naive HIV-HCV Co-Infected Alcohol Dependent Patient.
AB - HIV and HCV co-infection is a unique disease condition, and medical management of
such condition is difficult due to severity and systemic complications. Added
with heavy alcohol drinking, risk of liver injury increases due to several pro
inflammatory responses that subsequently get involved with alcohol metabolism.
Elevated levels of fatty acids have been reported both in viral infections as
well as alcoholic liver disease though such investigations have not addressed the
adverse events with dual viral infection of HIV and HCV along with heavy
drinking. This case report is of a patient with excessive alcohol drinking and
first time diagnosis of HIV and HCV dual infection, elaborating concurrent
alteration in Linoleic Acid (LA) levels and pro-inflammatory shift in omega
6/omega-3 ratio along with the elevations in liver injury markers. Elevated LA
has been recently studied extensively for its role in alcoholic liver disease;
and in the present case, we also found it to be clinically relevant to liver
injury.
PMID- 27489859
TI - The role of BRCA1-IRIS in ovarian cancer formation, drug resistance and
progression.
PMID- 27489860
TI - Ibrutinib repurposing: from B-cell malignancies to solid tumors.
PMID- 27489858
TI - Persistent infections, immune-senescence and Alzheimer's disease.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most
common cause of dementia. Classical hallmarks of AD such as amyloid deposition
and neurofibrillary tangles do not completely explain AD pathogenesis. Recent
investigations proposed Abeta peptide as an anti-microbial factor. Our previous
works suggested that the concomitant presence of single nucleotide polymorphisms
(SNPs) from AD genetic studies might impair antiviral defenses and increase the
individual susceptibility to herpes virus infection. Viruses of herpes family by
inducing frequent cycles of reactivation and latency constantly challenge the
immune response and drive the accumulation of memory T cells. However, the immune
system is not able to completely eradicate these viruses. The continuous antigen
stimulation activates chronic inflammatory responses that may progressively
induce neurodegenerative mechanisms in genetically susceptible elderly. The aim
of this paper is to suggest new perspectives in clinical pathogenesis of AD with
potential prevention and new medical treatment of the age associated cognitive
decline.
PMID- 27489861
TI - Hidden association of Cowden syndrome, PTEN mutation and meningioma frequency.
AB - Cowden syndrome (CS) is clinically presented by multiple hamartomas, often with
mucocutaneous lesions, goiter, breast cancer and gastrointestinal polyps. CS is a
genetic disorder of autosomal dominant inheritance and is one distinct syndrome
of the phosphatase and tensin homolog on chromosome 10 (PTEN) hamartoma tumor
spectrum. Noteworthy, PTEN germline mutations are related to a wide range of
brain tumors. We performed a systematic analysis and review of the medical
literature for Cowden syndrome and meningioma and additionally present the case
of a 29-year- old CS patient diagnosed with multiple meningiomas. We found strong
evidence for high incidence of brain tumors in CS patients. In particular
meningiomas and gangliocytomas/Lhermitte-Duclos disease were often associated
with 8% and 9% respectively in CS patients. Since aberrations in chromosome 10q
are associated with meningiomas, it is likely that the underlying mutations in CS
drive to a certain extent neoplastic meningioma growth. We propose to include
meningiomas and brain tumors in the major criteria spectrum of CS-related
disorders. This could warrant early diagnosis of brain lesions and close therapy,
as well as better monitoring of patients with CS.
PMID- 27489863
TI - Presence of both alterations in FGFR/FGF and PI3K/AKT/mTOR confer improved
outcomes for patients with metastatic breast cancer treated with PI3K/AKT/mTOR
inhibitors.
AB - There is limited data on co-expression of FGFR/FGR amplifications and PI3K/
AKT/mTOR alterations in breast cancer. Tumors from patients with metastatic
breast cancer referred to our Phase I Program were analyzed by next generation
sequencing (NGS). Genomic libraries were selected for all exons of 236 (or 182)
cancer-related genes sequenced to average depth of >500* in a CLIA laboratory
(Foundation Medicine, Cambridge, MA, USA) and analyzed for all classes of genomic
alterations. We report genomic profiles of 112 patients with metastatic breast
cancer, median age 55 years (range, 27-78). Twenty-four patients (21%) had at
least one amplified FGFR or FGF. Fifteen of the 24 patients (63%) also had an
alteration in the PI3K/ AKT/mTOR pathway. There was no association between
alterations in FGFR/FGF and PI3K/AKT/mTOR (P=0.49). Patients with simultaneous
amplification in FGFR/FGF signaling and the PI3K/AKT/mTOR pathway had a higher
rate of SD>=6 months/PR/ CR when treated with therapies targeting the
PI3K/AKT/mTOR pathway than patients with only alterations in the PI3K/AKT/mTOR
pathway (73% vs. 34%; P=0.0376) and remained on treatment longer (6.8 vs. 3.7
months; P=0.053). Higher response rates were seen in patients with simultaneous
amplification in FGFR/FGF signaling and alterations in the PI3K/AKT/mTOR pathway
who were treated with inhibitors of that pathway.
PMID- 27489862
TI - Durable response of glioblastoma to adjuvant therapy consisting of temozolomide
and a weekly dose of AMD3100 (plerixafor), a CXCR4 inhibitor, together with
lapatinib, metformin and niacinamide.
AB - Glioblastoma multiforme (GBM) is a CNS (central nervous system) malignancy with a
low cure rate. Median time to progression after standard treatment is 7 months
and median overall survival is 15 months [1]. Post-treatment vasculogenesis
promoted by recruitment of bone marrow derived cells (BMDCs, CD11b+
myelomonocytes) is one of main mechanisms of GBM resistance to initial
chemoradiotherapy treatment [2]. Local secretion of SDF-1, cognate ligand of
BMDCs CXCR4 receptors attracts BMDCs to the post-radiation tumor site.[3]. This
SDF-1 hypoxia-dependent effect can be blocked by AMD3100 (plerixafor) [4]. We
report a GBM case treated after chemo- radiotherapy with plerixafor and a
combination of an mTOR, a Sirt1 and an EGFRvIII inhibitor. After one year
temozolomide and the EGFRvIII inhibitor were stopped. Plerixafor, and the MTOR
and Sirt-1 inhibitors were continued. He is in clinical and radiologic remission
30 months from the initiation of his adjuvant treatment. To our knowledge, this
is the first report of a patient treated for over two years with a CXCR4
inhibitor (plerixafor), as part of his adjuvant treatment. We believe there is
sufficient experimental evidence to consider AMD3100 (plerixafor) part of the
adjuvant treatment of GBM. SIGNIFICANCE: The adjuvant inhibition of GBM
vasculogenesis(a process different from local angiogenesis) by specifically
blocking the migration of BMDCs to the primary tumor site with inhibitors of the
CXCR4/SDF-1 axis represents a potential novel therapeutic approach to GBM. There
is significant pre-clinical evidence and validation for its use as demonstrated
in a patient derived tumor xenograft model of GBM. Together with other specific
anti-tumoral therapies, the active inhibition of vasculogenesis in the adjuvant
treatment of GBM is deserving of further exploration.
PMID- 27489864
TI - Familial adenomatous patients with desmoid tumours show increased expression of
miR-34a in serum and high levels in tumours.
AB - Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a
subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy
to prevent cancer. DTs are a major cause of morbidity and mortality. The absence
of markers to monitor progression and a lack of treatment options are significant
limitations to clinical management. We investigated microRNAs (miRNA) levels in
DTs and serum using expression array analysis on two independent cohorts of FAP
patients (total, n=24). Each comprised equal numbers of patients who had formed
DTs (cases) and those who had not (controls). All controls had absence of DTs
confirmed by clinical and radiological assessment over at least three years post-
colectomy. Technical qPCR validation was performed using an expanded cohort (29
FAP patients; 16 cases and 13 controls). The most significant elevated serum
miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most
DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched
germline DNA did not detect mutations within the miR-34a-5p transcript sites or
3'-UTR of target genes that would alter functional miRNA activity. In conclusion,
miR-34a-5p is a potential circulatory marker and therapy target. A large
prospective world-wide multi-centre study is now warranted.
PMID- 27489865
TI - MRI phase changes in multiple sclerosis vs neuromyelitis optica lesions at 7T.
AB - OBJECTIVE: To characterize paramagnetic MRI phase signal abnormalities in
neuromyelitis optica spectrum disorder (NMOSD) vs multiple sclerosis (MS) lesions
in a cross-sectional study. METHODS: Ten patients with NMOSD and 10 patients with
relapsing-remitting MS underwent 7-tesla brain MRI including supratentorial T2*
weighted imaging and supratentorial susceptibility weighted imaging. Next, we
analyzed intra- and perilesional paramagnetic phase changes on susceptibility
weighted imaging filtered magnetic resonance phase images. RESULTS: We frequently
observed paramagnetic rim-like (75 of 232 lesions, 32%) or nodular (32 of 232
lesions, 14%) phase changes in MS lesions, but only rarely in NMOSD lesions (rim
like phase changes: 2 of 112 lesions, 2%, p < 0.001; nodular phase changes: 2 of
112 lesions, 2%, p < 0.001). CONCLUSIONS: Rim-like or nodular paramagnetic MRI
phase changes are characteristic for MS lesions and not frequently detectable in
NMOSD. Future prospective studies should ask whether these imaging findings can
be used as a biomarker to distinguish between NMOSD- and MS-related brain
lesions.
PMID- 27489866
TI - Lack of KIR4.1 autoantibodies in Japanese patients with MS and NMO.
AB - OBJECTIVES: To examine anti-KIR4.1 antibodies by 2 different assays in Japanese
patients with multiple sclerosis (MS) or neuromyelitis optica (NMO). METHODS: One
hundred sixty serum samples from 57 patients with MS, 40 patients with NMO/NMO
spectrum disorder (NMOSD), and 50 healthy controls (all were Japanese) were
tested with ELISA using a synthetic peptide of the first extracellular portion of
human KIR4.1. In addition, we attempted to detect anti-KIR4.1 immunoglobulin G in
the serum by the luciferase immunoprecipitation systems (LIPS) with the full
length of human KIR4.1 produced in a human cell line, which is highly sensitive
to single or multiple epitopes. RESULTS: We failed to detect antibodies to the
peptide fragment KIR4.1(83-120) in any case of MS and NMO/NMOSD using ELISA.
Antibodies to the recombinant full length of KIR4.1 protein were detected in only
2 patients with MS and none in the patients with NMO/NMOSD by the LIPS assay.
CONCLUSIONS: We developed 2 different methods (ELISA and LIPS) to measure
autoantibodies to KIR4.1 in serum. We detected anti-KIR4.1 immunoglobulin G at a
very low frequency in Japanese patients with MS or NMO/NMOSD. Serologic testing
for human KIR4.1-specific antibodies is unlikely to improve the diagnosis of MS
or NMO/NMOSD in Japanese patients.
PMID- 27489867
TI - Diffusion-weighted MR imaging of non-complicated hepatic cysts: Value of 3T
computed diffusion-weighted imaging.
AB - PURPOSE: To investigate the utility of computed 3T diffusion-weighted imaging (c
DWI) for the diagnosis of non-complicated hepatic cysts with a focus on the T2
shine-through effect. MATERIALS AND METHODS: In 50 patients with non-complicated
hepatic cysts we acquired one set of DWIs (b-value 0 and 1000 s/mm(2)) at 1.5T,
and two sets at 3T (b-value 0 and 1000 s/mm(2), TE 70 ms; b-value 0 and 600
s/mm(2), TE 60 ms). We defined the original DWIs acquired with b = 1000 s/mm(2)
at 1.5T and 3T as "o-1.5T-1000" and "o-3T-1000". c-DWIs were calculated with 3T
DWI at b-values of 0 and 600 s/mm(2). c-DWI with b = 1000 and 1500 s/mm(2) were
defined as "c-1000" and "c-1500". Radiologists evaluated the signal intensity
(SI) of the cysts using a 3-point score where 1 = not visible, 2 = discernible,
and 3 = clearly visible. They calculated the contrast ratio (CR) between the
cysts and the surrounding liver parenchyma on each DWIs and recorded the apparent
diffusion coefficient (ADC) with a b-value = 0 and 1000 s/mm(2) on 1.5T- and 3T
DWIs. RESULTS: Compared with o-1.5T-1000 DWI, the visual scores of all but the c
1500 DWIs were higher (p = 0.07 for c-1500- and p < 0.01 for the other DWIs). The
CR at b = 1000 s/mm(2) was higher on o-3T-1000- than on o-1.5T-1000- (p < 0.01)
but not higher than on c-1500 DWIs (p = 0.96). The CR at b = 0 s/mm(2) on 3T
images with TE 70 ms was higher than on 1.5T images (p < 0.01). The ADC value was
higher for 3T- than 1.5T images (p < 0.01). CONCLUSIONS: Non-complicated hepatic
cysts showed higher SI on o-3T-1000- than o-1.5T-1000 DWIs due to the T2-shine
through effect. This high SI was suppressed on c-1500 DWIs.
PMID- 27489868
TI - Locally advanced rectal cancer: Qualitative and quantitative evaluation of
diffusion-weighted MR imaging in the response assessment after neoadjuvant chemo
radiotherapy.
AB - PURPOSE: to investigate the added value of qualitative and quantitative
evaluation of diffusion weighted (DW) magnetic resonance (MR) imaging in response
assessment after neoadjuvant chemo-radiotherapy (CRT) in patients with locally
advanced rectal cancer (LARC). METHODS: 31 patients with LARC (stage >= T3) were
enrolled in the study. All patients underwent conventional MRI and DWI before
starting therapy and after neoadjuvant CRT. All patients underwent surgery;
pathologic staging represented the reference standard. For qualitative analysis,
two radiologists retrospectively reviewed conventional MR images and the combined
set of conventional and DW MR images and recorded their confidence level with
respect to complete response (ypCR). For quantitative analysis, tumor's apparent
diffusion coefficient (ADC) values were measured at each examination. ADC pre
CRT, ADC post-CRT and Delta ADC post-ADC pre of the three groups of response
(ypCR, partial response ypPR, stable disease ypSD) were compared. Receiver
operating characteristics (ROC) curve analysis was employed to investigate the
discriminatory capability for ypCR, responders (ypCR, ypPR) and ypSD of each
measure. RESULTS: addition of DWI to conventional T2-weighted sequences improved
diagnostic performance of MRI in the evaluation of ypCR. A low tumor ADC value in
the pre-CRT examination, a high ADC value in the post-CRT examination, a high
Delta ADC post-ADC pre [>0.3 (*10(-3) mm(2)/s)] were predictive of ypCR.
CONCLUSIONS: DW sequences improve MR capability to evaluate tumor response to
CRT. Nevertheless, no functional MR technique alone seems accurate enough to
safely select patients with ypCR.
PMID- 27489869
TI - Fiber tracking: A qualitative and quantitative comparison between four different
software tools on the reconstruction of major white matter tracts.
AB - PURPOSE: Diffusion tensor imaging (DTI) enables in vivo reconstruction of white
matter (WM) pathways. Considering the emergence of numerous models and fiber
tracking techniques, we herein aimed to compare, both quantitatively and
qualitatively, the fiber tracking results of four DTI software (Brainance,
Philips FiberTrak, DSI Studio, NordicICE) on the reconstruction of representative
WM tracts. MATERIALS AND METHODS: Ten healthy participants underwent 30
directional diffusion tensor imaging on a 3T-Philips Achieva TX MR-scanner. All
data were analyzed by two independent sites of experienced raters with the
aforementioned software and the following WM tracts were reconstructed:
corticospinal tract (CST); forceps major (Fmajor); forceps minor (Fminor);
cingulum bundle (CB); superior longitudinal fasciculus (SLF); inferior fronto
occipital fasciculus (IFOF). Visual inspection of the resulted tracts and
statistical analysis (inter-rater and betweensoftware agreement; paired t-test)
on fractional anisotropy (FA), axial and radial diffusivity (Daxial, Dradial)
were applied for qualitative and quantitative evaluation of DTI software results.
RESULTS: Qualitative evaluation of the extracted tracts confirmed anatomical
landmarks at least for the core part of each tract, even though differences in
the number of fibers extracted and the whole tract were evident, especially for
the CST, Fmajor, Fminor and SLF. Descriptive values did not deviate from the
expected range of values for healthy adult population. Substantial inter-rater
agreement (intraclass correlation coefficient [ICC], Bland-Altman analysis) was
found for all tracts (ICC; FA: 0.839-0.989, Daxial: 0.704-0.991, Dradial: 0.972
0.993). Low agreement for FA, Daxial and Dradial (ICC; Bland-Altman analysis) and
significant paired t-test differences (p < 0.05) were detected regarding between
software agreement. CONCLUSIONS: Qualitative comparison of four different DTI
software in addition to substantial inter-rater but poor between-software
agreement highlight the differences on existing fiber tracking methodologies and
several particularities of each WM tract, further supporting the need for further
study in both clinical and research settings.
PMID- 27489870
TI - Data resulting from the CFD analysis of ten window frames according to the UNI EN
ISO 10077-2.
AB - Data are related to the numerical simulation performed in the study entitled "CFD
modeling to evaluate the thermal performances of window frames in accordance with
the ISO 10077" (Malvoni et al., 2016) [1]. The paper focuses on the results from
a two-dimensional numerical analysis for ten frame sections suggested by the ISO
10077-2 and performed using GAMBIT 2.2 and ANSYS FLUENT 14.5 CFD code. The
dataset specifically includes information about the CFD setup and boundary
conditions considered as the input values of the simulations. The trend of the
isotherms points out the different impacts on the thermal behaviour of all
sections with air solid material or ideal gas into the cavities.
PMID- 27489871
TI - Primary leiomyosarcoma of the omentum presenting as an ovarian carcinoma, case
report and review of the literature.
AB - Primary omental leiomyosarcoma is a rare tumor. We report a case of successfully
resected omental leiomyosarcoma whose presentation mimicked ovarian carcinoma.
Symptoms of abdominal distension and discomfort that lasted 8 months followed by
pain lead to a diagnosis of a large mass in the abdomen. Physical examination
revealed a large, over 20 cm tumor, suspected to be of ovarian origin. A small
amount of ascites was found on Computerized Tomography (CT) and ultrasound (US)
scans. Total abdominal hysterectomy with bilateral salpingo-oophorectomy,
omentectomy and tumor debulking procedure was planned. Laparotomy revealed normal
uterus ovaries and tubes with a leiomyosarcoma of the omentum which was
completely resected successfully. Only 26 cases of primary leiomyosarcoma of the
omentum were previously described in the literature. A review of the literature
is also presented.
PMID- 27489872
TI - An individual with human immunodeficiency virus, dementia, and central nervous
system amyloid deposition.
AB - Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is
found in 30%-50% of individuals with HIV infection. To date, no HIV+ individual
has been reported to have a positive amyloid PET scan. We report a 71-year-old
HIV+ individual with HAND. Clinical and neuropsychologic evaluations confirmed a
progressive mild dementia. A routine brain MRI was normal for age.
[18F]Fluorodeoxyglucose-PET revealed mild hypermetabolism in bilateral basal
ganglia and hypometabolism of bilateral parietal cortex including the posterior
cingulate/precuneus. Resting state functional MRI revealed altered connectivity
as found with individuals with mild AD. CSF examination revealed a low
Abeta42/tau index but a low phospho-tau. An amyloid PET/CT with [18F]florbetaben
revealed pronounced cortical radiotracer deposition. This case report suggests
that progressive dementia in older HIV+ individuals may be due to HAND, AD, or
both. HIV infection does not preclude CNS Abeta/amyloid deposition. Amyloid PET
imaging may be of value in distinguishing HAND from AD pathologies.
PMID- 27489873
TI - Expanding the phenotypic associations of globular glial tau subtypes.
AB - INTRODUCTION: Clinicopathologic correlation in non-Alzheimer's tauopathies is
variable, despite refinement of pathologic diagnostic criteria. In the present
study, the clinical and neuroimaging characteristics of globular glial tauopathy
(GGT) were examined to determine whether subtyping according to consensus
guidelines improves clinicopathologic correlation. METHODS: Confirmed GGT cases
(n = 11) were identified from 181 frontotemporal tauopathy cases. Clinical and
neuroimaging details were collected, and cases sub-typed according to the
consensus criteria for GGT diagnosis. Relationships between clinical syndrome and
GGT subtype were investigated. RESULTS: In total, 11 patients (seven males, four
females, mean age = 67.3 +/- 10.6 years) with GGT were included. Most, but not
all, presented with behavioral variant frontotemporal dementia, but none had
amyotrophic lateral sclerosis. Subtyping of GGT proved to be difficult and did
not improve clinicopathologic correlation. DISCUSSION: Sub-classification of GGT
pathology may be difficult and did not improve clinicopathologic correlation.
Better biomarkers of tau pathology are needed.
PMID- 27489874
TI - Meeting physical activity recommendations may be protective against temporal lobe
atrophy in older adults at risk for Alzheimer's disease.
AB - INTRODUCTION: Physical activity (PA) is associated with brain health in older
adults. However, it is unknown whether the current physical activity
recommendations (PAR) impart substantive benefit. The objective of this study was
to compare temporal lobe volumes between older adults who met PAR and those who
did not. METHODS: Ninety-one enrollees from the Wisconsin Registry for
Alzheimer's Prevention wore an accelerometer for seven consecutive days to
quantify their PA behaviors and underwent a T-1 anatomic magnetic resonance
imaging scan. Participants were categorized as either having met PAR or not based
on the US Department of Health and Human Services recommendations of 150 minutes
of moderate-to-vigorous physical activity per week. RESULTS: Participants who met
PAR possessed significantly greater inferior (eta(2) P = .050) and anterior
(eta(2) P = .055) temporal lobe volumes compared with those who did not (P <
.05). DISCUSSION: Individuals at-risk for AD experience accelerated rates of
brain atrophy. These results suggest that regular engagement in PA at or above
PAR could attenuate this decline.
PMID- 27489876
TI - Progression and predictors of mild cognitive impairment in Chinese elderly: A
prospective follow-up in the Shanghai Aging Study.
AB - INTRODUCTION: The Shanghai Aging Study is a community-based study aiming to
investigate the incidence and progression of cognitive decline in Chinese
elderly, with the operational procedures and diagnostic criteria similar to
cohort studies in developed countries. METHODS: We prospectively evaluated 362
individuals with mild cognitive impairment (MCI) diagnosed at baseline through a
clinical and neuropsychological interview. Diagnoses of dementia and MCI were
made using standard criteria via consensus diagnosis. RESULTS: The conversion
rate to dementia was 6.0 per 100 person-years, while the reversion rate to
cognitive normal was 7.8 per 100 person-years. Amnestic MCI multiple domains was
the most risky type for dementia (conversion rate: 14.2 per 100 person-years).
Older age (hazard ratio [HR] = 1.09), apolipoprotein E (APOE epsilon4) (HR =
2.15), and low MMSE score (HR = 1.18) were predictors for dementia. DISCUSSION:
Approximately 6% of elderly with MCI progress to dementia annually. Prospective
studies are needed to further examine risk and protective predictors and to seek
proper interventions for cognitive decline.
PMID- 27489875
TI - White matter hyperintensities are more highly associated with preclinical
Alzheimer's disease than imaging and cognitive markers of neurodegeneration.
AB - INTRODUCTION: Cognitive tests and nonamyloid imaging biomarkers do not
consistently identify preclinical AD. The objective of this study was to evaluate
whether white matter hyperintensity (WMH) volume, a cerebrovascular disease
marker, is more associated with preclinical AD than conventional AD biomarkers
and cognitive tests. METHODS: Elderly controls enrolled in the Alzheimer's
Disease Neuroimaging Initiative (ADNI, n = 158) underwent florbetapir-PET scans,
psychometric testing, neuroimaging with MRI and PET, and APOE genetic testing.
Elderly controls the Parkinson's progression markers initiative (PPMI, n = 58)
had WMH volume, cerebrospinal fluid (CSF) Abeta1-42, and APOE status measured.
RESULTS: In the ADNI cohort, only WMH volume and APOE epsilon4 status were
associated with cerebral Abeta (standardized beta = 0.44 and 1.25, P = .03 and
.002). The association between WMH volume and APOE epsilon4 status with cerebral
Abeta (standardized beta = 1.12 and 0.26, P = .048 and .045) was confirmed in the
PPMI cohort. DISCUSSION: WMH volume is more highly associated with preclinical AD
than other AD biomarkers.
PMID- 27489877
TI - A missed detection of prodromal dementia may be the worst enemy of a timely
diagnosis.
PMID- 27489879
TI - Relationship between the Activities of Daily Living Questionnaire and the
Montreal Cognitive Assessment.
AB - INTRODUCTION: The Activities of Daily Living Questionnaire (ADL-Q) is an
informant report questionnaire assessing functional impairment in daily living
skills. Previous research has demonstrated correlations between ADL-Q and
cognitive screening measures among patients with dementia. This study examined
the relationship between ADL-Q and the Montreal Cognitive Assessment (MoCA), a
brief cognitive screening. METHODS: Records of 448 individuals from an outpatient
neurology clinic were reviewed. Pearson correlations were calculated between ADL
Q scores and MoCA scores. Linear regression models were fit using demographic
information to predict ADL-Q scores. MoCA scores were then added to the models to
determine the increase in predictive value of the MoCA. RESULTS: Lower MoCA
scores were associated with higher levels of functional impairment. For each
model, adding the MoCA significantly improved model fit. DISCUSSION: Low scores
on the MoCA, among patient's presenting for memory complaints, should raise
concerns about functional decline and prompt for further assessment of functional
ability.
PMID- 27489878
TI - Untangling tau imaging.
AB - In vivo imaging of tau deposits is providing a better understanding of the
temporal and spatial tau deposition in the brain, allowing a more comprehensive
insight into the causes, diagnoses, and potentially treatment of tauopathies such
as Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome,
chronic traumatic encephalopathy, and some variants of frontotemporal lobar
degeneration. The assessment of tau deposition in the brain over time will allow
a deeper understanding of the relationship between tau and other variables such
as cognition, genotype, and neurodegeneration, as well as assessing the role tau
plays in ageing. Preliminary human studies suggest that tau imaging could also be
used as a diagnostic, prognostic, and theranostic biomarker, as well as a
surrogate marker for target engagement, patient recruitment, and efficacy
monitoring for disease-specific therapeutic trials.
PMID- 27489880
TI - Cognitive variability-A marker for incident MCI and AD: An analysis for the
Alzheimer's Disease Neuroimaging Initiative.
AB - INTRODUCTION: The potential of intra-individual cognitive variability (IICV) to
predict incident mild cognitive impairment (MCI) or Alzheimer's disease (AD) was
examined and compared to well-established neuroimaging and genetic predictors.
METHODS: IICV was estimated using four neuropsychological measures for n = 1324
Alzheimer's Disease Neuroimaging Initiative (ADNI) participants who were
cognitively healthy or diagnosed with MCI at baseline. IICV was used to predict
time to incident MCI or AD, and compared to hippocampal volume loss and APOE
epsilon4 status via survival analysis. RESULTS: In survival analyses, controlling
for age, education, baseline diagonosis, and APOE epsilon4 status, likelihood
ratio tests indicate that IICV is associated with time to cognitive status change
in the full sample (P < .0001), and when the sample was restricted to individuals
with MCI at baseline (P < .0001). DISCUSSION: These findings suggest IICV may be
a low-cost, noninvasive alternative to traditional AD biomarkers.
PMID- 27489881
TI - The association between pulse pressure change and cognition in late life: Age and
where you start matters.
AB - INTRODUCTION: Variations across studies in the association between blood pressure
(BP) and cognition might be explained partly by duration of exposure to
hypertension and partly by nonrandom attrition over time. Pulse pressure (PP)
reflects arterial stiffness which may better reflect chronicity of hypertension.
METHODS: Over six annual cycles, 1954 individuals aged 65+ years from a
prospective population-based cohort underwent BP measurements and cognitive
evaluations. We examined the relationship of change in five cognitive domains to
longitudinal PP patterns across the late-life age spectrum, before and after
stratifying by baseline systolic blood pressure (SBP) and adjusting for
attrition. RESULTS: There were four longitudinal PP patterns: stable normal,
stable high, increasing, and decreasing. Those with lower baseline SBP and an
increasing or stable high PP had less decline in cognition, an effect that was
attenuated with aging. Among those with higher baseline SBP, there were no
differences across PP groups, but increasing age was consistently associated with
greater cognitive decline. DISCUSSION: The effect of PP on cognitive decline
depends on age, baseline SBP, and the trajectory of PP change. Cardiovascular
mechanisms underlying cognitive aging should be recognized as nuanced and dynamic
processes when exploring prevention and treatment targets in the elderly, so that
the optimal timing and type of intervention can be identified.
PMID- 27489883
TI - A systematic pipeline for the objective comparison of whole-brain spectroscopic
MRI with histology in biopsy specimens from grade III glioma.
AB - The diagnosis, prognosis, and management of patients with gliomas are largely
dictated by the pathological analysis of tissue biopsied from a selected region
within the lesion. However, due to the heterogeneous and infiltrative nature of
gliomas, identifying the optimal region for biopsy with conventional magnetic
resonance imaging (MRI) can be quite difficult. This is especially true for low
grade gliomas, which often are non-enhancing tumors. To improve the management of
patients with these tumors, the field of neuro-oncology requires an imaging
modality that can specifically identify a tumor's most anaplastic/aggressive
region(s) for biopsy targeting. The addition of metabolic mapping using
spectroscopic MRI (sMRI) to supplement conventional MRI could improve biopsy
targeting and, ultimately, diagnostic accuracy. Here, we describe a pipeline for
the integration of state-of-the-art, high-resolution whole-brain 3D sMRI maps
into a stereotactic neuronavigation system for guiding biopsies in gliomas with
nonenhancing components. We also outline a machine-learning method for automated
histology analysis that generates normalized, quantitative metrics describing
tumor infiltration in immunohistochemically-stained tissue specimens. As a proof
of concept, we describe the combination of these two techniques in a small cohort
of grade III glioma patients. In this work, we aim to set forth a systematic
pipeline to stimulate histopathology-image validation of advanced MRI techniques,
such as sMRI.
PMID- 27489882
TI - Developing and Conducting a Dissertation Study through the Community-Based
Participatory Research Approach.
AB - The community-based participatory research (CBPR) approach has been shown to be
innovative and effective in conducting research with communities experiencing
health disparities. Doctoral nursing students, and other doctoral students in the
health sciences, who are interested in this approach can benefit through
structured CBPR training experiences in learning how to engage with communities,
build community capacity, share resources, implement CBPR study plans, and
disseminate results of CBPR-focused studies. The objectives of this case-study
are to demonstrate ways in which one doctoral student aligned with academic
mentors and a funded CBPR project to build a relationship with the Sikh Asian
Indian (AI) community of New York City to develop and implement a CBPR-focused
doctoral dissertation study. The purpose of the research was to examine the
relationship between the experience of perceived discrimination and health
outcomes in this community. CBPR methods utilized in developing the study
entailed the author partaking in formal and informal CBPR learning experiences,
building relationships with community and academic partners early on through
volunteering, developing a research plan in collaboration with members of the
community and academic partners, identifying an appropriate setting and methods
for recruitment and data collection, increasing capacity and resources for all
partners (the author, community, and academic), and presenting dissertation study
findings to the community. In conclusion, CBPR-focused doctoral experiences are
novel pedagogical and professional approaches for nursing and health science
students which can lead to mutual benefits for all involved, and ultimately
successful and effective community-based health research.
PMID- 27489884
TI - Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic
asthma in early life.
AB - Asthma is a chronic inflammatory airways disease that usually begins in early
life and involves gene-environment interactions. Although most asthma exhibits
allergic inflammation, many allergic individuals do not have asthma. Here, we
report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as
local tissue susceptibility gene that promotes allergic asthma. We show that
enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways
and plays a role in airway remodeling, independent of inflammation. Furthermore,
remodeling and inflammation are both suppressed in Adam33-null mice after
allergen challenge. When induced in utero or added ex vivo, sADAM33 causes
structural remodeling of the airways, which enhances postnatal airway
eosinophilia and bronchial hyperresponsiveness following subthreshold challenge
with an aeroallergen. This substantial gene-environment interaction helps to
explain the end-organ expression of allergic asthma in genetically susceptible
individuals. Finally, we show that sADAM33-induced airway remodeling is
reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma.
PMID- 27489885
TI - Protective and detrimental effects of neuroectodermal cell-derived tissue factor
in mouse models of stroke.
AB - Within the CNS, a dysregulated hemostatic response contributes to both
hemorrhagic and ischemic strokes. Tissue factor (TF), the primary initiator of
the extrinsic coagulation cascade, plays an essential role in hemostasis and also
contributes to thrombosis. Using both genetic and pharmacologic approaches, we
characterized the contribution of neuroectodermal (NE) cell TF to the
pathophysiology of stroke. We used mice with various levels of TF expression and
found that astrocyte TF activity reduced to ~5% of WT levels was still sufficient
to maintain hemostasis after hemorrhagic stroke but was also low enough to
attenuate inflammation, reduce damage to the blood-brain barrier, and improve
outcomes following ischemic stroke. Pharmacologic inhibition of TF during the
reperfusion phase of ischemic stroke attenuated neuronal damage, improved
behavioral deficit, and prevented mortality of mice. Our data demonstrate that NE
cell TF limits bleeding complications associated with the transition from
ischemic to hemorrhagic stroke and also contributes to the reperfusion injury
after ischemic stroke. The high level of TF expression in the CNS is likely the
result of selective pressure to limit intracerebral hemorrhage (ICH) after
traumatic brain injury but, in the modern era, poses the additional risk of
increased ischemia-reperfusion injury after ischemic stroke.
PMID- 27489886
TI - A Conceptual Framework for the Progression of Balance Exercises in Persons with
Balance and Vestibular Disorders.
AB - There is little information in peer-reviewed literature to specifically guide the
choice of exercise for persons with balance and vestibular disorders. The purpose
of this study is to provide a rationale for the establishment of a progression
framework and propose a logical sequence in progressing balance exercises for
persons with vestibular disorders. Our preliminary conceptual framework was
developed by a multidisciplinary team of physical therapists and engineers with
extensive experience with people with vestibular disorders. Balance exercises are
grouped into six different categories: static standing, compliant surface, weight
shifting, modified center of gravity, gait, and vestibulo-ocular reflex (VOR).
Through a systematized literature review, interviews and focus group discussions
with physical therapists and postural control experts, and pilot studies
involving repeated trials of each exercise, exercise progressions for each
category were developed and ranked in order of degree of difficulty. Clinical
expertise and experience guided decision making for the exercise progressions.
Hundreds of exercise combinations were discussed and research is ongoing to
validate the hypothesized rankings. The six exercise categories can be
incorporated into a balance training program and the framework for exercise
progression can be used to guide less experienced practitioners in the
development of a balance program. It may also assist clinicians and researchers
to design, develop, and progress interventions within a treatment plan of care,
or within clinical trials. A structured exercise framework has the potential to
maximize postural control, decrease symptoms of dizziness/visual vertigo, and
provide "rules" for exercise progression for persons with vestibular disorders.
The conceptual framework may also be applicable to persons with other balance
related issues.
PMID- 27489887
TI - Innervation of Gill Lateral Cells in the Bivalve Mollusc Crassostrea virginica
Affects Cellular Membrane Potential and Cilia Activity.
AB - Gill lateral cells of Crassostrea virginica are innervated by the branchial
nerve, which contains serotonergic and dopaminergic fibers that regulate cilia
beating rate. Terminal release of serotonin or dopamine results in an increase or
decrease, respectively, of cilia beating rate in lateral gill cells. In this
study we used the voltage sensitive fluorescent probe DiBAC4(3) to quantify
changes in gill lateral cell membrane potential in response to electrical
stimulation of the branchial nerve or to applications of serotonin and dopamine,
and correlate these changes to cilia beating rates. Application of serotonin to
gill lateral cells caused prolonged membrane depolarization, similar to plateau
potentials, while increasing cilia beating rate. Application of dopamine
hyperpolarized the resting membrane while decreasing cilia beating rate. Low
frequency (5 Hz) electrical stimulations of the branchial nerve, which cause
terminal release of endogenous serotonin, or high frequency (20 Hz) stimulations,
which cause terminal release of endogenous dopamine, had the same effects on gill
lateral cell membrane potentials and cilia beating rate as the respective
applications of serotonin or dopamine. The study shows that innervation of gill
lateral cells by the branchial nerve affects membrane potential as well as cilia
beating rate, and demonstrates a strong correlation between changes in membrane
potential and regulation of cilia beating rate. The study furthers the
understanding of serotonin and dopamine signaling in the innervation and
regulation of gill cilia in bivalves. The study also shows that voltage sensitive
fluorescent probes like DiBAC 4(3) can be successfully used as an alternative to
microelectrodes to measure changes in membrane potential of ciliated gill cells
and other small cells with fast moving cilia.
PMID- 27489888
TI - Methods to Reduce Medication Errors in a Clinical Trial of an Investigational
Parenteral Medication.
AB - There are few evidence-based guidelines to inform optimal design of complex
clinical trials, such as those assessing the safety and efficacy of intravenous
drugs administered daily with infusion times over many hours per day and
treatment durations that may span years. This study is a retrospective review of
inpatient administration deviation reports for an investigational drug that is
administered daily with infusion times of 8-24 hours, and variable treatment
durations for each patient. We report study design modifications made in 2007
2008 aimed at minimizing deviations from an investigational drug infusion
protocol approved by an institutional review board and the United States Food and
Drug Administration. Modifications were specifically aimed at minimizing errors
of infusion rate, incorrect dose, incorrect patient, or wrong drug administered.
We found that the rate of these types of administration errors of the study drug
was significantly decreased following adoption of the specific study design
changes. This report provides guidance in the design of clinical trials testing
the safety and efficacy of study drugs administered via intravenous infusion in
an inpatient setting so as to minimize drug administration protocol deviations
and optimize patient safety.
PMID- 27489889
TI - Fabrication of an "ion-imprinting" dual-emission quantum dot nanohybrid for
selective fluorescence turn-on and ratiometric detection of cadmium ions.
AB - In this work, we have fabricated a new dual-emission quantum dot (QD) nanohybrid
for fluorescence ratiometric determination of cadmium ions (Cd2+) in water
samples, where the "turn-on" model and "ion-imprinting" technique were
incorporated simultaneously. The nanohybrid probe was composed of green-emitting
CdSe QDs covalently linked onto the surface of silica nanoparticles embedded with
red-emitting CdTe QDs. The chemical etching of ethylene diamine tetraacetic acid
(EDTA) at the surface produced specific Cd2+ recognition sites and quenched the
green fluorescence of outer CdSe QDs. Upon exposure to different amounts of Cd2+,
the green fluorescence was gradually restored, whereas the inner red fluorescence
remained constant. As a consequence, an obviously distinguishable fluorescence
color variation (from red to green) of the probe solution was observed. Under the
optimized conditions, the developed ratiometric sensor displayed a linear
response range from 0.1 to 9 MUM with a detection limit of 25 nM (S/N = 3) for
Cd2+, which could offer an alternative sensing approach for the highly sensitive
and selective detection of heavy metal ions.
PMID- 27489890
TI - Functional group migrations between boron and metal centres within transition
metal-borane and -boryl complexes and cleavage of H-H, E-H and E-E' bonds.
AB - This feature article examines some of the recent advances in the chemistry of Z
type transition metal-borane and X-type transition metal-boryl complexes. It
focuses on the employment of these boron-based functionalities acting as stores
and transfer agents for functional groups such as hydrides, alkyl groups and aryl
groups which can either be abstracted or delivered to the metal centre. The
review also explores the rather novel reactivity involving the cleavage of H-H, E
H and E-E' bonds (where E and E' are a range of groups) across the transition
metal-boron bond in such complexes. It explores the early examples of the
addition of H-H across transition metal-borane bonds and describes the new
transformation in the context of other known modes of hydrogen activation
including classic oxidative addition and heterolytic cleavage at transition metal
centres as well as Frustrated Lewis Pair chemistry. Similar reactivity involving
transition metal-boryl complexes are also described particularly those which
undergo both boryl-to-borane and borane-to-borohydride transformations. The
delivery of hydride to the metal centre in combination with the potential to
regenerate the borohydride functional group via a recharging process is explored
in the context of providing a new strategy for catalysis. Finally, a light
hearted look at the analogy of the 'stinging processes' involving Trofimenko type
ligands is taken one step further to determine whether it is indeed in the nature
of scorpionate ligands to repeatedly 'sting' just as the real life scorpions do.
PMID- 27489892
TI - CardioPulse. The Korean Society of Cardiology.
PMID- 27489891
TI - CardioPulse. Francesco Cosentino MD PhD FESC, from Rome to the Karolinska
Institute in Stockholm via the Mayo Clinic.
PMID- 27489893
TI - Update on preoperative assessment for geriatric patients prior to elective
surgery.
PMID- 27489894
TI - HHS Lays Out Multifaceted Plan to Combat Opioid Abuse.
PMID- 27489895
TI - Time Running Out for Physicians to Review Open Payments Data.
PMID- 27489897
TI - HHS Says Basic Standards of Transparency Would Simplify Process for Sharing
Patient Data.
PMID- 27489896
TI - MedPAC Tackles Complex Issue of Low-Value Medical Services.
PMID- 27489898
TI - Move to Protect Hospital-Employed Family Physicians Seen as Patient Advocacy.
PMID- 27489899
TI - [Diabetes mellitus and chronic kidney disease: Possibilities of prediction, early
diagnosis, and nephroprotection in the 21st century].
AB - The. review gives data on the prognostic value of genetic markers when analyzing
the risk of chronic kidney disease in diabetes mellitus, those on new
possibilities of early diagnosis of diabetic nephropathy using urinary biomarkers
(nephrinuria, podocinuria) and proteomic urinalysis at the stage of
normoalbuminuria. The interpretation of the index mrcroalbuminuria in type 2
diabetesis critically analyzed. The nephroprotective properties of novel classes
of glucose-lowering drugs, such as incretins and gliflozins, are considered.
PMID- 27489900
TI - Students Trained at Public Medical Schools Are More Likely to Practice in
Primary Care.
PMID- 27489901
TI - [Idiopathic membranous nephropathy: Evolution in understanding the problem].
AB - The review highlights the evolution of ideas on the. mechanisms responsible for
the 'development of membranous nephropathy(MN), glomerulopathy that is the most
common cause of nephrotic syndrome in adults. Primary emphasis is placed on the
primary form of MN. The important step to understanding the nature of this
clinical and morphological form of glomerulonephritis is to create its animal
model (Heymann nephritis), then to decipher the mechanisms of immune complex
damage (complement activation,a role of cellular immunity), and to identify
autoantigens responsible for the development of idiopathic MN in man
(podocyteneutral endopeptidase, transmembrane M-type phospholipase A2 receptor,
thrombospondin type-1 domain-containing 7A. The findings constituted the basis
for developing current methods for the diagnosis and treatment of MN, including
the pathogenetically sound inhibition of autoantibody production, as well as a
molecular orientation effect on podocyte dysfunction.
PMID- 27489902
TI - [Difficulties in correcting hyperphosphatemia in patients with chronic renal
failure. A place of noncalcium-containing phosphate-binding drugs].
AB - The review considers the current views of the mechanisms of hyperphosphatemia in
patients with chronic renal failure. It shows indications for the use of
different classes of phosphate-binding drugs to correct hyperphosphatemia.
PMID- 27489903
TI - [The efficiency of antiviral therapy in patients with chronic -hepatitis C
infected with hepatitis C virus recombinants].
AB - The review gives the data available in the literature in the efficiency of
treatment in patients with chronic hepatitis C infected with hepatitis C
virus.(HCV) recombinants, by applying various antiviral therapy regimens. The low
efficiency of treatment with- pegylated interferons (PEG IFN) + ribavirin (RIB)
and sofosburin (SOF) +RIB in this patient group (a sustained virologic response
was achieved in 22 and 30.7%, respectively) compared with the efficiency of
treatment (87-97 and 83-97%, respectively) inpatients infected with HCV genotype
2 does not allow the 2015 EASL HCV genotype 2 treatment regimens to be used in.
such patients. In this connection, subtyping genotype 2 isolates by NS5B
sequencing should be introduced into clinical laboratory practice to successfully
detect recombinant HCVs and to enhance the efficiency of antiviral therapy.
PMID- 27489905
TI - Groups advise house committee against changes to ACIP processes.
PMID- 27489906
TI - Free CME available for using HHS' new opioid training tool.
PMID- 27489904
TI - [Chronic kidney disease and atrial fibrillation as components of the cardiorenal
continuum].
AB - The paper discusses the present-day idea on a relationship between atrial
fibrillation and chronic kidney dis~ase, the specific features of therapeutic
policy, and the place of antithrombotic therapy in particular."Based on the
results of population-based studies,the authors set forth the specific features
of cardiac arrhythmias concurrent with kidney injury, as well as promising
directions to optimize management schemes for this category of patients.
PMID- 27489907
TI - New resource helps physicians encourage Tdap vaccination for pregnant patients.
PMID- 27489908
TI - Sudden onset bilateral lower limb weakness in a female patient with no
significant past medical history.
PMID- 27489909
TI - Groups Prod HHS to Recognize Advance Care Planning CPT Codes.
PMID- 27489911
TI - GAO Levels Sharp Criticism Against Physician Fee Committee.
PMID- 27489910
TI - FDA Denies Request to Weaken Smokeless Tobacco Warning.
PMID- 27489912
TI - AAFP Warns FTC About Consequences of Insurance Mergers.
PMID- 27489913
TI - Suicide.
PMID- 27489916
TI - Practices Make Progress on Alternative Payment Models, but Struggles Remain.
PMID- 27489915
TI - CMS Clarifies Use of CCM Code in Medicare Advantage Plans.
PMID- 27489914
TI - Evert Joost Dorhout Mees.
PMID- 27489917
TI - Register Now for Midwest's First Direct Primary Care Summit.
PMID- 27489918
TI - Health Coaches Help Family Physicians Improve Chronic Disease Management.
PMID- 27489919
TI - Two doctors who put Worcester on the medical heritage map.
PMID- 27489920
TI - Additional comment to "Survey of prenatal testing for genetic disorders in
Japan: Recent report".
PMID- 27489921
TI - In Memoriam: A Tribute to Alan Magill.
PMID- 27489922
TI - Interview with Rose Leke: Urging Female Scientists to Shoot for the Moon.
PMID- 27489943
TI - Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in
a Lipid Bilayer.
AB - Mapping the conformational landscape of G protein-coupled receptors (GPCRs), and
in particular how this landscape is modulated by the membrane environment, is
required to gain a clear picture of how signaling proceeds. To this end, we have
developed an original strategy based on solution-state nuclear magnetic resonance
combined with an efficient isotope labeling scheme. This strategy was applied to
a typical GPCR, the leukotriene B4 receptor BLT2, reconstituted in a lipid
bilayer. Because of this, we are able to provide direct evidence that BLT2
explores a complex landscape that includes four different conformational states
for the unliganded receptor. The relative distribution of the different states is
modulated by ligands and the sterol content of the membrane, in parallel with the
changes in the ability of the receptor to activate its cognate G protein. This
demonstrates a conformational coupling between the agonist and the membrane
environment that is likely to be fundamental for GPCR signaling.
PMID- 27489944
TI - Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in
Reservoir-Host Populations.
AB - Progress in combatting zoonoses that emerge from wildlife is often constrained by
limited knowledge of the biology of pathogens within reservoir hosts. We focus on
the host-pathogen dynamics of four emerging viruses associated with bats: Hendra,
Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and
domestic animals often coincides with pulses of viral excretion within bat
populations, but the mechanisms driving such pulses are unclear. Three hypotheses
dominate current research on these emerging bat infections. First, pulses of
viral excretion could reflect seasonal epidemic cycles driven by natural
variations in population densities and contact rates among hosts. If lifelong
immunity follows recovery, viruses may disappear locally but persist globally
through migration; in either case, new outbreaks occur once births replenish the
susceptible pool. Second, epidemic cycles could be the result of waning immunity
within bats, allowing local circulation of viruses through oscillating herd
immunity. Third, pulses could be generated by episodic shedding from persistently
infected bats through a combination of physiological and ecological factors. The
three scenarios can yield similar patterns in epidemiological surveys, but
strategies to predict or manage spillover risk resulting from each scenario will
be different. We outline an agenda for research on viruses emerging from bats
that would allow for differentiation among the scenarios and inform development
of evidence-based interventions to limit threats to human and animal health.
These concepts and methods are applicable to a wide range of pathogens that
affect humans, domestic animals, and wildlife.
PMID- 27489945
TI - Socioeconomic Disadvantage Moderates the Association between Peripheral
Biomarkers and Childhood Psychopathology.
AB - BACKGROUND: Socioeconomic disadvantage (SED) has been consistently associated
with early life mental health problems. SED has been shown to impact multiple
biological systems, including the regulation of neurotrophic proteins, immune
inflammatory and oxidative stress markers, which, conversely, have been reported
to be relevant to physiological and pathological neurodevelopment This study
investigated the relationship between SED, different domains of psychopathology,
serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance
(TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a
composite of socioeconomic risk would be associated with psychopathology and
altered levels of peripheral biomarkers. In addition, we hypothesized that SED
would moderate the associations between mental health problems, IL6, TBARS and
BDNF. METHODS AND FINDINGS: Using a cross-sectional design, we measured the serum
levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated
socio-demographic characteristics and mental health problems using the Child
Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a
cumulative risk model. Generalized linear models were used to assess associations
between SED, biomarkers levels and psychopathology. SED was significantly
associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020)
and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between
SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066,
p = 0.077). SED was also significantly associated with all CBCL DSM-oriented
scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were
associated with specific subscales. Moreover, the associations between serum
biomarkers and domains of psychopathology were moderated by SED, with stronger
correlations between mental health problems, IL6, TBARS, and BDNF being observed
in children with high SED. CONCLUSIONS: In children, SED is highly associated
with mental health problems. Our findings suggest that this association may be
moderated via effects on multiple interacting neurobiological systems.
PMID- 27489946
TI - Domain Architectures and Grain Boundaries in Chemical Vapor Deposited Highly
Anisotropic ReS2 Monolayer Films.
AB - Recent studies have shown that vapor phase synthesis of structurally isotropic
two-dimensional (2D) MoS2 and WS2 produces well-defined domains with clean grain
boundaries (GBs). This is anticipated to be vastly different for 2D anisotropic
materials like ReS2 mainly due to large anisotropy in interfacial energy imposed
by its distorted 1T crystal structure and formation of signature Re-chains along
[010] b-axis direction. Here, we provide first insight on domain architecture on
chemical vapor deposited (CVD) ReS2 domains using high-resolution scanning
transmission electron microscopy, angle-resolved nano-Raman spectroscopy,
reflectivity, and atomic force microscopy measurements. Results provide ways to
achieve crystalline anisotropy in CVD ReS2, establish domain architecture of high
symmetry ReS2 flakes, and determine Re-chain orientation within subdomains.
Results also provide a first atomic resolution look at ReS2 GBs, and surprisingly
we find that cluster and vacancy defects, formed by collusion of Re-chains at the
GBs, dramatically impact the crystal structure by changing the Re-chain direction
and rotating Re-chains 180 degrees along their b-axis. Overall results not only
shed first light on domain architecture and structure of anisotropic 2D systems
but also allow one to attain much desired crystalline anisotropy in CVD grown
ReS2 for the first time for tangible applications in photonics and
optoelectronics where direction-dependent dichroic and linearly polarized
material properties are required.
PMID- 27489948
TI - When the Minority Thinks "Essentially" Like the Majority: Blacks Distinguish Bio
Somatic from Bio-Behavioral Essentialism in Their Conceptions of Whites, and Only
the Latter Predicts Prejudice.
AB - Essentialist beliefs about social groups can contribute to prejudice and
intergroup distancing. To date, little data have been gathered regarding minority
group members' essentialistic thinking about the White majority in the U.S. Do
essentialist beliefs show a similar structure when minority group members are
thinking about the majority as when the majority group is thinking about the
minority group? Do minority group essentialist beliefs predict affective
prejudice and diminished desire for intergroup contact as they do among White
respondents? We sought answers to these questions in a study that included 248
African American participants. We found clear evidence that the structure of
Blacks' essentialist thinking about Whites matches the structure of Whites'
essentialist thinking about Blacks. Specifically, Black respondents made a
distinction between bio-somatic and bio-behavioral essentialism, and reported
stronger endorsement of the former as compared to the latter. Also replicating
prior studies of Whites' essentialist thinking, only bio-behavioral essentialist
beliefs were predictive of negative attitudes. This suggests that essentialism
can be linked to prejudice even in contexts that do not involve a dominant group
rationalizing its social advantages. Discussion centers on implications of this
work for prejudice reduction.
PMID- 27489949
TI - Recurrent Inhibition to the Medial Nucleus of the Trapezoid Body in the Mongolian
Gerbil (Meriones Unguiculatus).
AB - Principal neurons in the medial nucleus of the trapezoid body (MNTB) receive
strong and temporally precise excitatory input from globular bushy cells in the
cochlear nucleus through the calyx of Held. The extremely large synaptic currents
produced by the calyx have sometimes led to the view of the MNTB as a simple
relay synapse which converts incoming excitation to outgoing inhibition. However,
electrophysiological and anatomical studies have shown the additional presence of
inhibitory glycinergic currents that are large enough to suppress action
potentials in MNTB neurons at least in some cases. The source(s) of glycinergic
inhibition to MNTB are not fully understood. One major extrinsic source of
glycinergic inhibitory input to MNTB is the ventral nucleus of the trapezoid
body. However, it has been suggested that MNTB neurons receive additional
inhibitory inputs via intrinsic connections (collaterals of glycinergic
projections of MNTB neurons). While several authors have postulated their
presence, these collaterals have never been examined in detail. Here we test the
hypothesis that collaterals of MNTB principal cells provide glycinergic
inhibition to the MNTB. We injected dye into single principal neurons in the
MNTB, traced their projections, and immunohistochemically identified their
synapses. We found that collaterals terminate within the MNTB and provide an
additional source of inhibition to other principal cells, creating an inhibitory
microcircuit within the MNTB. Only about a quarter to a third of MNTB neurons
receive such collateral inputs. This microcircuit could produce side band
inhibition and enhance frequency tuning of MNTB neurons, consistent with
physiological observations.
PMID- 27489947
TI - The Estrogen Receptor alpha-Cistrome Beyond Breast Cancer.
AB - Although many tissues express estrogen receptor (ER)alpha, most studies focus on
breast cancer where ERalpha occupies just a small fraction of its total
repertoire of potential DNA-binding sites, based on sequence. This raises the
question: Can ERalpha occupy these other potential binding sites in a different
context? Ligands, splice variants, posttranslational modifications, and acquired
mutations of ERalpha affect its conformation, which may alter chromatin
interactions. To date, literature describes the DNA-binding sites of ERalpha (the
ERalpha cistrome) in breast, endometrium, liver, and bone, in which the receptor
mainly binds to enhancers. Chromosomal boundaries provide distinct areas for
dynamic gene regulation between tissues, where the usage of enhancers deviates.
Interactions of ERalpha with enhancers and its transcriptional complex depend on
the proteome, which differs per cell type. This review discusses the biological
variables that influence ERalpha cistromics, using reports from human specimens,
cell lines, and mouse tissues, to assess whether ERalpha genomics in breast
cancer can be translated to other tissue types.
PMID- 27489952
TI - Correlation of 3D FLAIR and Dopamine Transporter Imaging in Patients With
Parkinsonism.
AB - OBJECTIVE: The purpose of this study is to evaluate direct in vivo visualization
of nigrosome-1 in substantia nigra (SN) with 3D FLAIR imaging and its diagnostic
value in predicting the intactness of presynaptic dopaminergic function of the
nigrostriatal pathway. MATERIALS AND METHODS: Forty-five patients showing
parkinsonism who underwent both 3D FLAIR and dopamine transporter (DAT) imaging
were recruited. In total, 90 SNs were reviewed on axial 3D FLAIR images. We
regarded oval or linear hyperintensities on the posterolateral side of SN as
intact nigrosome-1. Two neuroradiologists independently evaluated the appearance
of nigrosome-1, and disagreements were settled by consensus. Kappa values for
interrater agreement were calculated. Diagnostic performances of the appearance
of nigrosome-1 for predicting presynaptic dopaminergic function on DAT imaging
and Parkinson disease (PD) were calculated. RESULTS: The diagnostic performances
of a loss of nigrosome-1 on 3D FLAIR images were sensitivity of 85.7%,
specificity of 85.4%, positive predictive value (PPV) of 83.7%, and negative
predictive value (NPV) of 87.2% for predicting impaired presynaptic dopaminergic
function on DAT imaging, and sensitivity of 94.7%, specificity of 76.9%, PPV of
85.7%, and NPV of 90.9% for predicting PD. When only oval hyperintensity was
considered as intact nigrosome-1, its sensitivity and NPV were increased up to
95.2% and 91.7%, respectively, for predicting impaired presynaptic dopaminergic
function on DAT imaging, and both increased to 100% for predicting PD.
Interobserver agreement for the appearance of nigrosome-1 on 3D FLAIR images was
substantial (kappa = 0.625). CONCLUSION: Nigrosome-1 could be visualized on 3D
FLAIR images, and its loss can be used to predict presynaptic dopaminergic
function and to diagnose PD with high accuracy.
PMID- 27489950
TI - Antibiotic-Induced Gut Microbiota Disruption Decreases TNF-alpha Release by
Mononuclear Cells in Healthy Adults.
AB - OBJECTIVES: Broad-spectrum antibiotics disrupt the intestinal microbiota. The
microbiota is essential for physiological processes, such as the development of
the gut immune system. Recent murine data suggest that the intestinal microbiota
also modulates systemic innate immune responses; however, evidence in humans is
lacking. METHODS: Twelve healthy young men were given oral broad-spectrum
antibiotics (ciprofloxacin 500 mg bid, vancomycin 500 mg tid and metronidazole
500 mg tid) for 7 days. At baseline, 1 day, and 6 weeks after antibiotics, blood
and feces were sampled. Whole blood and isolated mononuclear cells were
stimulated with selected Toll-like receptor agonists and heat-killed bacteria.
Microbiota diversity and composition was determined using bacterial 16S rDNA
sequencing. RESULTS: One day after the antibiotic course, microbial diversity was
significantly lower compared with baseline. After antibiotic therapy, systemic
mononuclear cells produced lower levels of tumor necrosis factor (TNF)-alpha
after ex vivo stimulation with lipopolysaccharide (LPS). This diminished capacity
to produce TNF-alpha was restored 6 weeks after cessation of antibiotic therapy.
In whole blood, a reduced capacity to release interleukin (IL)-1beta and IL-6 was
observed after LPS stimulation. Antibiotic treatment did not impact on
differential leukocyte counts, phagocytosis, and cell surface markers of
neutrophils and monocytes. CONCLUSIONS: In this proof-of-principle study of
healthy subjects, microbiota disruption by broad-spectrum antibiotics is
reversibly associated with decreased systemic cellular responsiveness towards
LPS. The implications of these findings in a clinical setting remain to be
determined.
PMID- 27489951
TI - Fructose 1,6-Bisphosphate Aldolase, a Novel Immunogenic Surface Protein on
Listeria Species.
AB - Listeria monocytogenes is a ubiquitous food-borne pathogen, and its presence in
food or production facilities highlights the importance of surveillance.
Increased understanding of the surface exposed antigens on Listeria would provide
potential diagnostic and therapeutic targets. In the present work, using mass
spectrometry and genetic cloning, we show that fructose-1,6-bisphosphate aldolase
(FBA) class II in Listeria species is the antigen target of the previously
described mAb-3F8. Western and dot blot assays confirmed that the mAb-3F8 could
distinguish all tested Listeria species from close-related bacteria. Localization
studies indicated that FBA is present in every fraction of Listeria cells,
including supernatant and the cell wall, setting Listeria spp. as one of the few
bacteria described to have this protein on their cell surface. Epitope mapping
using ORFeome display and a peptide membrane revealed a 14-amino acid peptide as
the potential mAb-3F8 epitope. The target epitope in FBA allowed distinguishing
Listeria spp. from closely-related bacteria, and was identified as part of the
active site in the dimeric enzyme. However, its function in cell surface seems
not to be host cell adhesion-related. Western and dot blot assays further
demonstrated that mAb-3F8 together with anti-InlA mAb-2D12 could differentiate
pathogenic from non-pathogenic Listeria isolated from artificially contaminated
cheese. In summary, we report FBA as a novel immunogenic surface target useful
for the detection of Listeria genus.
PMID- 27489953
TI - Supervised Learning for Detection of Duplicates in Genomic Sequence Databases.
AB - MOTIVATION: First identified as an issue in 1996, duplication in biological
databases introduces redundancy and even leads to inconsistency when
contradictory information appears. The amount of data makes purely manual de
duplication impractical, and existing automatic systems cannot detect duplicates
as precisely as can experts. Supervised learning has the potential to address
such problems by building automatic systems that learn from expert curation to
detect duplicates precisely and efficiently. While machine learning is a mature
approach in other duplicate detection contexts, it has seen only preliminary
application in genomic sequence databases. RESULTS: We developed and evaluated a
supervised duplicate detection method based on an expert curated dataset of
duplicates, containing over one million pairs across five organisms derived from
genomic sequence databases. We selected 22 features to represent distinct
attributes of the database records, and developed a binary model and a multi
class model. Both models achieve promising performance; under cross-validation,
the binary model had over 90% accuracy in each of the five organisms, while the
multi-class model maintains high accuracy and is more robust in generalisation.
We performed an ablation study to quantify the impact of different sequence
record features, finding that features derived from meta-data, sequence identity,
and alignment quality impact performance most strongly. The study demonstrates
machine learning can be an effective additional tool for de-duplication of
genomic sequence databases. All Data are available as described in the
supplementary material.
PMID- 27489954
TI - Dialect Interference in Lexical Processing: Effects of Familiarity and Social
Stereotypes.
AB - BACKGROUND/AIMS: The current study explored the roles of dialect familiarityand
social stereotypes in dialect interference effects in a speeded lexical
classification task. METHODS: Listeners classified the words bad and bed or had
and head produced by local Midland and non-local Northern talkers and the words
sod and side or rod and ride produced by non-local, non-stereotyped Northern and
nonlocal, stereotyped Southern talkers in single- and mixed-talker blocks.
RESULTS: Lexical classification was better for the local dialect than for the non
local dialects, and for the stereotyped non-local dialect than for the non
stereotyped non-local dialect. Dialect interference effects were observed for all
three dialects, although the patterns of interference differed. For the local
dialect, dialect interference was observed for response times, whereas for the
non-local dialects, dialect interference was observed primarily for accuracy.
CONCLUSION: These findings reveal complex interactions between indexical and
lexical information in speech processing.
PMID- 27489955
TI - SNVSniffer: an integrated caller for germline and somatic single-nucleotide and
indel mutations.
AB - BACKGROUND: Various approaches to calling single-nucleotide variants (SNVs) or
insertion-or-deletion (indel) mutations have been developed based on next
generation sequencing (NGS). However, most of them are dedicated to a particular
type of mutation, e.g. germline SNVs in normal cells, somatic SNVs in
cancer/tumor cells, or indels only. In the literature, efficient and integrated
callers for both germline and somatic SNVs/indels have not yet been extensively
investigated. RESULTS: We present SNVSniffer, an efficient and integrated caller
identifying both germline and somatic SNVs/indels from NGS data. In this
algorithm, we propose the use of Bayesian probabilistic models to identify SNVs
and investigate a multiple ungapped alignment approach to call indels. For
germline variant calling, we model allele counts per site to follow a multinomial
conditional distribution. For somatic variant calling, we rely on paired tumor
normal pairs from identical individuals and introduce a hybrid subtraction and
joint sample analysis approach by modeling tumor-normal allele counts per site to
follow a joint multinomial conditional distribution. A comprehensive performance
evaluation has been conducted using a diversity of variant calling benchmarks.
For germline variant calling, SNVSniffer demonstrates highly competitive accuracy
with superior speed in comparison with the state-of-the-art FaSD, GATK and
SAMtools. For somatic variant calling, our algorithm achieves comparable or even
better accuracy, at fast speed, than the leading VarScan2, SomaticSniper,
JointSNVMix2 and MuTect. CONCLUSIONS: SNVSniffers demonstrates the feasibility to
develop integrated solutions to fast and efficient identification of germline and
somatic variants. Nonetheless, accurate discovery of genetic variations is
critical yet challenging, and still requires substantially more research efforts
being devoted. SNVSniffer and synthetic samples are publicly available at
http://snvsniffer.sourceforge.net .
PMID- 27489957
TI - Thoracoamniotic Shunts in Macrocystic Lung Lesions: Case Series and Review of the
Literature.
AB - OBJECTIVE: To evaluate the efficiency of thoracoamniotic shunts for drainage of
macrocystic-type congenital cystic adenomatoid malformation (CCAM). SUBJECTS AND
METHODS: This was a retrospective study of 12 fetuses with a large thoracic cyst
treated with thoracoamniotic shunting between 2004 and 2014 in a tertiary fetal
therapy center. Medline was searched to identify cases of CCAM treated with
thoracoamniotic shunting. RESULTS: In all cases the thoracic cyst was associated
with major mediastinal shift, the CCAM volume ratio (CVR) was >1.6, and in eight
cases there was associated hydrops. Shunt insertion was successfully carried out
in all cases at a median gestational age of 24 weeks (range 18-34). In 10 cases
there was live birth at a median age of 38 weeks (range 35-41), but in two
hydropic fetuses there was intrauterine death. A literature search identified a
total of 98 fetuses with CCAM treated with thoracoamniotic shunting between 1987
and 2016. In the combined data from the previous and the current study, the
survival rate was 77% (53 of 69) for hydropic and 90% (37 of 41) for nonhydropic
fetuses. CONCLUSIONS: The role of thoracoamniotic shunting in macrocystic lung
lesions associated with hydrops is well accepted. Intrauterine intervention is
also likely to be beneficial in the subgroup of nonhydropic fetuses with a CVR
>1.6.
PMID- 27489956
TI - Comparison of Brachyspira hyodysenteriae Isolates Recovered from Pigs in
Apparently Healthy Multiplier Herds with Isolates from Herds with Swine
Dysentery.
AB - Swine dysentery (SD) is a mucohaemorrhagic colitis of grower/finisher pigs
classically resulting from infection by the anaerobic intestinal spirochaete
Brachyspira hyodysenteriae. This study aimed to determine whether B.
hyodysenteriae isolates from pigs in three healthy German multiplier herds
supplying gilts to other farms differed from isolates from nine German production
herds with SD. Isolates were subjected to whole genomic sequencing, and in silico
multilocus sequence typing showed that those from the three multiplier herds were
of previously undescribed sequence types (ST132, ST133 and ST134), with all
isolates from the same herd having the same ST. All isolates were examined for
the presence of 332 genes encoding predicted virulence or virulence lifestyle
associated factors, and these were well conserved. Isolates from one multiplier
herd were atypical in being weakly haemolytic: they had 10 amino acid
substitutions in the haemolysin III protein and five in the haemolysin activation
protein compared to reference strain WA1, and had a disruption in the promoter
site of the hlyA gene. These changes likely contribute to the weakly haemolytic
phenotype and putative lack of virulence. These same isolates also had nine base
pair insertions in the iron metabolism genes bitB and bitC and lacked five of six
plasmid genes that previously have been associated with colonisation. Other
overall differences between isolates from the different herds were in genes from
three of five outer membrane proteins, which were not found in all the isolates,
and in members of a block of six plasmid genes. Isolates from three herds with SD
had all six plasmid genes, while isolates lacking some of these genes were found
in the three healthy herds-but also in isolates from six herds with SD. Other
differences in genes of unknown function or in gene expression may contribute to
variation in virulence; alternatively, superior husbandry and better general
health may have made pigs in the two multiplier herds colonised by "typical"
strongly haemolytic isolates less susceptible to disease expression.
PMID- 27489959
TI - Scale and Sampling Effects on Floristic Quality.
AB - Floristic Quality Assessment (FQA) is increasingly influential for making land
management decisions, for directing conservation policy, and for research. But,
the basic ecological properties and limitations of its metrics are ill defined
and not well understood-especially those related to sample methods and scale.
Nested plot data from a remnant tallgrass prairie sampled annually over a 12-year
period, were used to investigate FQA properties associated with species detection
rates, species misidentification rates, sample year, and sample grain/area. Plot
size had no apparent effect on Mean C (an area's average Floristic Quality
level), nor did species detection levels above 65% detection. Simulated species
misidentifications only affected Mean C values at greater than 10% in large
plots, when the replaced species were randomly drawn from the broader county-wide
species pool. Finally, FQA values were stable over the 12-year study, meaning
that there was no evidence that the metrics exhibit year effects. The FQA metric
Mean C is demonstrated to be robust to varied sample methodologies related to
sample intensity (plot size, species detection rate), as well as sample year.
These results will make FQA measures even more appealing for informing land-use
decisions, policy, and research for two reasons: 1) The sampling effort needed to
generate accurate and consistent site assessments with FQA measures is shown to
be far lower than what has previously been assumed, and 2) the stable properties
and consistent performance of metrics with respect to sample methods will allow
for a remarkable level of comparability of FQA values from different sites and
datasets compared to other commonly used ecological metrics.
PMID- 27489960
TI - Correction: Metastases and Colon Cancer Tumor Growth Display Divergent Responses
to Modulation of Canonical WNT Signaling.
AB - [This corrects the article DOI: 10.1371/journal.pone.0150697.].
PMID- 27489961
TI - Ambient Engineering for High-Performance Organic-Inorganic Perovskite Hybrid
Solar Cells.
AB - Considering the evaporation of solvents during fabrication of perovskite films,
the organic ambience will present a significant influence on the morphologies and
properties of perovskite films. To clarify this issue, various ambiences of N,N
dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and chlorobenzene (CBZ) are
introduced during fabrication of perovskite films by two-step sequential
deposition method. The results reveal that an ambient CBZ atmosphere is favorable
to control the nucleation and growth of CH3NH3PbI3 grains while the others
present a negative effect. The statistical results show that the average
efficiencies of perovskite solar cells processed in an ambient CBZ atmosphere can
be significantly improved by a relatively average value of 35%, compared with
those processed under air. The efficiency of the best perovskite solar cells can
be improved from 10.65% to 14.55% by introducing this ambience engineering
technology. The CH3NH3PbI3 film with large-size grains produced in an ambient CBZ
atmosphere can effectively reduce the density of grain boundaries, and then the
recombination centers for photoinduced carriers. Therefore, a higher short
circuit current density is achieved, which makes main contribution to the
improvement in efficiency. These results provide vital progress toward
understanding the role of ambience in the realization of highly efficient
perovskite solar cells.
PMID- 27489958
TI - Fzd4 Haploinsufficiency Delays Retinal Revascularization in the Mouse Model of
Oxygen Induced Retinopathy.
AB - Mutations in genes that code for components of the Norrin-FZD4 ligand-receptor
complex cause the inherited childhood blinding disorder familial exudative
vitreoretinopathy (FEVR). Statistical evidence from studies of patients at risk
for the acquired disease retinopathy of prematurity (ROP) suggest that rare
polymorphisms in these same genes increase the risk of developing severe ROP,
implying that decreased Norrin-FZD4 activity predisposes patients to more severe
ROP. To test this hypothesis, we measured the development and recovery of
retinopathy in wild type and Fzd4 heterozygous mice in the absence or presence of
ocular ischemic retinopathy (OIR) treatment. Avascular and total retinal vascular
areas and patterning were determined, and vessel number and caliber were
quantified. In room air, there was a small delay in retinal vascularization in
Fzd4 heterozygous mice that resolved as mice reached maturity suggestive of a
slight defect in retinal vascular development. Subsequent to OIR treatment there
was no difference between wild type and Fzd4 heterozygous mice in the vaso
obliterated area following exposure to high oxygen. Importantly, after return of
Fzd4 heterozygous mice to room air subsequent to OIR treatment, there was a
substantial delay in retinal revascularization of the avascular area surrounding
the optic nerve, as well as delayed vascularization toward the periphery of the
retina. Our study demonstrates that a small decrease in Norrin-Fzd4 dependent
retinal vascular development lengthens the period during which complications from
OIR could occur.
PMID- 27489964
TI - The Applicability of Plantar Padding in Reducing Peak Plantar Pressure in the
Forefeet of Healthy AdultsImplications for the Foot at Risk.
AB - BACKGROUND: We investigated the effectiveness and durability of two types of
plantar padding, the plantar metatarsal pad and the single wing plantar cover,
which are commonly used for reducing forefoot plantar pressures. METHODS: Mean
peak plantar pressure and impulse at the hallux and at the first, second, third,
and fourth metatarsophalangeal joints across both feet were recorded using the
two-step method in 18 individuals with normal asymptomatic feet. Plantar paddings
were retained for 5 days, and their durability and effectiveness were assessed by
repeating the foot plantar measurement at baseline and after 3 and 5 days.
RESULTS: The single wing plantar cover devised from 5-mm felt adhesive padding
was effective and durable in reducing peak plantar pressure and impulse at the
first metatarsophalangeal joint (P = .001 and P = .015, respectively); however,
it was not found to be effective in reducing peak plantar pressure and impulse at
the hallux (P = .782 and P = .845, respectively). The plantar metatarsal pad was
not effective in reducing plantar forefoot pressure and impulse at the second,
third, and fourth metatarsophalangeal joints (P = .310 and P = .174,
respectively). CONCLUSIONS: These results imply limited applicability of the
single wing plantar cover and the plantar metatarsal pad in reducing hallux
pressure and second through fourth metatarsophalangeal joint pressure,
respectively. However, the single wing plantar cover remained durable for the 5
days of the trial and was effective in reducing the peak plantar pressure and
impulse underneath the first metatarsophalangeal joint.
PMID- 27489966
TI - Effect of Asymmetrical Load Carrying on Joint Kinetics of the Lower Extremity
During Walking in High-Heeled Shoes in Young Women.
AB - BACKGROUND: Carrying a load asymmetrically and walking in high-heeled shoes are
common in women. Knowledge of the effects of the two combined conditions on lower
limb kinetics is lacking. We sought to examine the effects of walking in high
heeled shoes and carrying an asymmetrical load on the joint kinetics of the lower
extremity in young women. METHODS: Fifteen participants were asked to walk in
flat-heeled and 9-cm high-heeled shoes and to asymmetrically carry loads of 0%
body weight (BW), 5% BW, and 10% BW. The three-dimensional joint moments of the
hip, knee, and ankle in each of the walking conditions were studied through
ground reaction force measurements and motion analysis. RESULTS: Walking in high
heeled shoes and asymmetrically carrying a load of 5% or 10% BW resulted in
significant differences in ankle joint moments of the loaded and unloaded lower
limbs. Compared with walking in flat-heeled shoes, walking in high-heeled shoes
and carrying a load asymmetrically significantly increased hip extension, hip
abduction, knee extension, and knee adduction moments and decreased ankle plantar
moment of the loaded leg. Walking in high-heeled shoes carrying a load of 10% BW
resulted in greater significant changes in hip abduction, knee extension, and
ankle dorsiflexion moments in the loaded leg than did carrying a load of 5% BW.
CONCLUSIONS: These findings indicate that walking in high-heeled shoes and
asymmetrical load carrying create significant differences in joint loading
between the two limbs and alter lower-extremity kinetics.
PMID- 27489962
TI - An Optimized Small Tissue Handling System for Immunohistochemistry and In Situ
Hybridization.
AB - Recent development in 3D printing technology has opened an exciting possibility
for manufacturing 3D devices on one's desktop. We used 3D modeling programs to
design 3D models of a tissue-handling system and these models were "printed" in a
stereolithography (SLA) 3D printer to create precision histology devices that are
particularly useful to handle multiple samples with small dimensions in parallel.
Our system has been successfully tested for in situ hybridization of zebrafish
embryos. Some of the notable features include: (1) A conveniently transferrable
chamber with 6 mesh-bottomed wells, each of which can hold dozens of zebrafish
embryos. This design allows up to 6 different samples to be treated per chamber.
(2) Each chamber sits in a well of a standard 6-well tissue culture plate. Thus,
up to 36 different samples can be processed in tandem using a single 6 well
plate. (3) Precisely fitting lids prevent solution evaporation and condensation,
even at high temperatures for an extended period of time: i.e., overnight
riboprobe hybridization. (4) Flat bottom mesh maximizes the consistent treatment
of individual tissue samples. (5) A magnet-based lifter was created to handle up
to 6 chambers (= 36 samples) in unison. (6) The largely transparent resin aids in
convenient visual inspection both with eyes and using a stereomicroscope. (7)
Surface engraved labeling enables an accurate tracking of different samples. (8)
The dimension of wells and chambers minimizes the required amount of precious
reagents. (9) Flexible parametric modeling enables an easy redesign of the 3D
models to handle larger or more numerous samples. Precise dimensions of 3D models
and demonstration of how we use our devices in whole mount in situ hybridization
are presented. We also provide detailed information on the modeling software, 3D
printing tips, as well as 3D files that can be used with any 3D printer.
PMID- 27489965
TI - Treatment of Ingrown Toenail with a Shape Memory Alloy Device.
AB - BACKGROUND: We sought to report the clinical results of a new conservative
treatment modality that uses a shape memory alloy device in patients with ingrown
toenail. METHODS: A retrospective review was performed on 41 patients with
ingrown toenail treated with the K-D device (S&C Biotech, Seoul, South Korea)
between April 2013 and July 2014. Recurrence rate, cosmetic results, pain during
the treatment period, and patient satisfaction were the major outcome measures.
RESULTS: Patients were followed for at least 6 months (mean +/- SD, 8.6 +/- 2.1
months; range, 6-12 months). Recurrence was seen in eight patients (19.5%). Mean
time to recurrence was 6.2 months (range, 3-10 months). Thirty-one patients
(75.6%) were satisfied with the treatment. Thirty-five patients (85.4%) rated the
application and treatment period as painless, and the remaining six (14.6%) noted
pain particularly during shoe wearing. Thirty-one patients (75.6%) rated the
cosmetic results as "excellent," four (9.8%) as "acceptable," and six (14.6%) as
"poor." Satisfaction with the treatment, the cosmetic results, and pain were
significantly worse in patients with recurrence (P = .0001 for all). All of the
patients returned to their work immediately after application of the device. No
complications occurred. CONCLUSIONS: The K-D device is a safe and effective
treatment method for ingrown toenail. Although the recurrence rate is higher than
for surgical treatment methods, the K-D device is a practical and painless method
that provides immediate return to work and daily activities and excellent or
acceptable cosmesis in most patients.
PMID- 27489963
TI - Meltwater export of prokaryotic cells from the Greenland ice sheet.
AB - Microorganisms are flushed from the Greenland Ice Sheet (GrIS) where they may
contribute towards the nutrient cycling and community compositions of downstream
ecosystems. We investigate meltwater microbial assemblages as they exit the GrIS
from a large outlet glacier, and as they enter a downstream river delta during
the record melt year of 2012. Prokaryotic abundance, flux and community
composition was studied, and factors affecting community structures were
statistically considered. The mean concentration of cells exiting the ice sheet
was 8.30 * 104 cells mL-1 and we estimate that ~1.02 * 1021 cells were
transported to the downstream fjord in 2012, equivalent to 30.95 Mg of carbon.
Prokaryotic microbial assemblages were dominated by Proteobacteria,
Bacteroidetes, and Actinobacteria. Cell concentrations and community compositions
were stable throughout the sample period, and were statistically similar at both
sample sites. Based on our observations, we argue that the subglacial environment
is the primary source of the river-transported microbiota, and that cell export
from the GrIS is dependent on discharge. We hypothesise that the release of
subglacial microbiota to downstream ecosystems will increase as freshwater flux
from the GrIS rises in a warming world.
PMID- 27489967
TI - Normal Values of Pressures and Foot Areas Measured in the Static Condition.
AB - BACKGROUND: Podiatric physicians are increasingly using pedobarographs to measure
plantar pressure. However, normal values of static pedobarographic variables for
healthy men and women are lacking, which makes it difficult to evaluate abnormal
foot positioning in standing patients with low- or high-arched feet or painful
feet. METHODS: During upright standing, a computerized pedobarograph measured the
maximal (Pmax) and mean (Pmean) plantar pressures, total foot area, and forefoot
and rearfoot areas in 84 healthy women and 84 healthy men, aged 18 to 83 years.
After calibration of the pedobarograph, a correction factor was applied to area
measurements, and data repeatability was assessed. RESULTS: The Pmax and Pmean
values were not correlated with age but with weight, body mass index, and shoe
size. Total foot area was significantly higher in male participants and
correlated with body weight, body mass index, and shoe size but not with age. In
both sexes, forefoot area was significantly lower than rearfoot area. Significant
positive correlations were observed between forefoot and rearfoot areas and
weight and shoe size. The forefoot-rearfoot area ratio did not vary with sex,
weight, shoe size, and age. CONCLUSIONS: These data provide relationships between
Pmax, Pmean, and foot areas and weight and shoe size and clearly indicate no age
dependence of pedobarographic data. They also provide stable values of the
forefoot-rearfoot area ratio. These data should help clinicians evaluate abnormal
foot placement in standing patients.
PMID- 27489969
TI - Surgical Reconstruction of the Forefoot with Hallux Valgus Associated with
Metatarsus Adductus.
AB - Metatarsus adductus is a structural deformity that may be associated with hallux
valgus and that may lead to metatarsal pain and functional abnormality of the
foot. Correcting hallux valgus is complicated in these cases because of the
deviation in adduction of the lesser metatarsals, especially the second
metatarsal that occupies the first intermetatarsal space. We report the case of a
49-year-old man who underwent a scarf osteotomy in the first metatarsal,
shortening and abductor oblique distal osteotomies of the lesser metatarsals, and
arthrodesis of the central toes with Z-lengthening of the capsule and long
extensor tendons of the toes.
PMID- 27489968
TI - Synovial Sarcoma in the Foot of a 5-Year-Old ChildA Case Report.
AB - The purpose of this case report is to present a rare finding of synovial sarcoma
in a 5-year-old child. Most soft-tissue masses of the foot are too often presumed
to be small and benign; therefore, compared with soft-tissue sarcomas, they are
difficult to clinically differentiate and treat. A 5-year-old girl presented with
a painful lesion that was diagnosed as synovial sarcoma after an excisional
biopsy was performed. This was an unexpected finding of synovial sarcoma
involving the tibialis posterior tendon of her right foot. The patient presented
with an 8-month history of tenderness and an antalgic gait. We would like to
encourage that all soft-tissue tumors of the foot be preoperatively evaluated
with the aid of diagnostic imaging so that a well-planned biopsy assessment can
be performed, with adequate margins excised.
PMID- 27489971
TI - Erratum.
PMID- 27489970
TI - Charcot's Neuroarthropathy After Simultaneous Pancreas-Kidney TransplantA Case
Report.
AB - Simultaneous pancreas-kidney transplant (SPKT) is an accepted approach and the
treatment of choice in patients with type 1 diabetes with accompanying end-stage
renal disease. Charcot's neuroarthropathy of the foot (CN) is a fairly common and
devastating complication found in patients with long-standing, mostly
uncontrolled, diabetes. However, CN has also been identified as a posttransplant
consequence of SPKT. Traditional postoperative immunosuppressive therapy,
particularly the use of corticosteroids, is acknowledged as an additional risk
factor for the development of de novo CN after SPKT. This article describes an
unusual case of a patient who presented with full-blown CN deformity after SPKT.
PMID- 27489972
TI - A Novel Method of Quantifying Gait Deviations Using Plantar Pressure Patterns.
AB - BACKGROUND: Comparing the dynamic pedobarographic patterns of individuals is
common practice in basic and applied research. However, this process is often
time-consuming and complex, and commercially available software often lacks
powerful visualization and interpretation tools. METHODS: We propose a simple
method for displaying pixel-level pedobarographic deviations over time relative
to a so-called reference pedobarographic pattern. This novel method contains four
distinct automated preprocessing stages: 1) normalization of pedobarographic
fields (for foot length and width), 2) temporal normalization, 3) a pixel-level z
score-based calculation, and 4) color coding of the normalized pedobarographic
fields. Group and patient-level comparisons were illustrated using an
experimental data set including diabetic and nondiabetic patients. RESULTS: The
automated procedure was found to be robust and quantified distinct temporal
deviations in pedobarographic fields. CONCLUSIONS: The advantages of the novel
method cover several domains, including visualization, interpretation, and
education.
PMID- 27489973
TI - "Pilot Hole" Technique for Interphalangeal Joint Fusion of Toes.
AB - Fusion of an interphalangeal joint of a lesser toe is a commonly used procedure
for addressing interphalangeal joint deformities such as a hammer or a claw toe.
Fusion can be achieved by insertion of an intramedullary Kirschner wire in a
retrograde manner. Deviation of the Kirschner wire from the intramedullary canal
into the surrounding soft tissues is common. This can render the fusion unstable
and can cause painful soft-tissue irritation and early Kirschner wire loosening,
resulting in an unstable nonunion with recurrence of deformity. We describe a
simple and reproducible technique to assist with optimal intramedullary placement
of the Kirschner wire, thereby reducing the risk of complications after
interphalangeal joint fusion of a toe.
PMID- 27489974
TI - Building Effective Partnerships Between Vascular Surgeons and Podiatric
Physicians in the Effective Management of Diabetic Foot Ulcers.
AB - Both vascular surgeons and podiatric physicians care for patients with diabetic
foot ulcerations (DFUs), one of today's most challenging health-care populations
in the United States. The prevalence of DFUs has steadily increased, along with
the rising costs associated with care. Because of the numerous comorbidities
affecting these patients, it is necessary to take a multidisciplinary approach in
the management of these patients. Such efforts, primarily led by podiatric
physicians and vascular surgeons, have been shown to effectively decrease major
limb loss. Establishing an interprofessional partnership between vascular surgery
and podiatric medicine can lead to an improvement in the delivery of care and
outcomes of this vulnerable patient population.
PMID- 27489975
TI - Working Our Plan.
PMID- 27489980
TI - In Situ Investigations of Laser-Generated Ligand-Free Platinum Nanoparticles by X
ray Absorption Spectroscopy: How Does the Immediate Environment Influence the
Particle Surface?
AB - Pulsed laser ablation in liquid (PLAL) has proven its usefulness as a
nanoparticle (NP) synthesis method alternative to traditional chemical reduction
methods, where the absence of any molecular ligands or residual reactants makes
laser-generated nanoparticles ideal reference materials for charge-transfer
experiments. We synthesized additive-free platinum nanoparticles by PLAL and in
situ characterized their interaction with H2O, sodium phosphate buffer, and
sodium citrate as well as a TiO2 support by X-ray absorption fine structure
(XAFS), i.e., X-ray absorption near-edge structure (XANES) and extended X-ray
absorption fine structure (EXAFS). Differences in the white-line intensity among
the colloidal particles in the three liquids indicate that the respective NP
solvent interaction varies in strength. The ions added ex situ diffuse through
the particles' electric double layer and interact electrostatically with the
Stern plane. Consequently, these ions weaken the interaction of the functional OH
groups that are bound to the partially oxidized platinum surfaces and cause their
partial reduction. Comparing XAFS spectra of laser-generated Pt NPs in citrate
with wet-chemically synthesized ones (both ligand-covered) indicates different
types of Pt-O bonds: a Pt(IV)O2 type in the case of wet-chemical NPs and a
Pt(II)O type in the case of laser-generated NPs. A comparison of unsupported
laser-generated platinum NPs in H2O with TiO2-supported ones shows no white-line
intensity differences and also an identical number of Pt-O bonds in both cases.
This suggests that in the deposition process at least part of the double-layer
coating stays intact and that the ligand-free Pt particle properties are
preserved in the TiO2-supported Pt particles, relevant for heterogeneous
catalysis.
PMID- 27489981
TI - Beat-to-beat T-wave alternans detection using the Ensemble Empirical Mode
Decomposition method.
AB - BACKGROUND: T-wave alternans (TWA) is defined as a consistent variation in the
repolarization morphology that repeats on every other beat. This study aimed to
evaluate beat-to-beat TWA detection using the Ensemble EMD (EEMD) method. METHOD:
A total of 108 recordings of standard 12-lead ECGs of 69 healthy subjects (17
females, 42+/-18 years; 52 males, 40+/-13 years) and 39 cardiac-condition
patients (ischemic cardiomyopathy; ICM and dilated cardiomyopathy; DCM) with left
ventricular ejection fractions (LVEF) <=40% were studied. We first determined the
QT interval of ECG via a template matching algorithm. Then, beat-to-beat T-waves
were extracted to quantify beat-to-beat TWA. The EEMD method was applied to the T
wave time series to decompose them into a set of intrinsic mode functions (IMFs).
The instantaneous frequency was measured by performing the Hilbert transform on
the selected IMF for extracting the features. Four different classifiers were
applied to the extracted features to assess and classify the existence of TWA in
the ECG signal. RESULTS: In the simulation study, the global classifier worked
better than the subject-based classifier for detecting alternans in the T-waves.
In addition, the average accuracy and sensitivity for detecting TWA were greater
than 80%. In the real Holter ECG data obtained from Toronto General Hospital, the
Ensemble classifier had higher classification accuracy, 74%, than other
classifiers and a positive predictive value of 100%. CONCLUSION: In conclusion,
the proposed Ensemble EMD method with Ensemble classifier can be utilized for
detecting beat-to-beat TWA in the ECG signal.
PMID- 27489982
TI - Venous thromboembolism in patients with hematologic malignancy and
thrombocytopenia.
AB - The optimal management of hematologic malignancy-associated venous
thromboembolism (VTE) in patients with moderate-to-severe thrombocytopenia is
unclear. This is a retrospective study of 128 adult patients with hematologic
malignancies who were diagnosed with VTE. The outcome of patients with
significant thrombocytopenia (<=50,000/uL) was compared with those without. Forty
seven patients (36.7%) had a platelet count <=50,000/uL during a period of time
of perceived need for new or continued anticoagulation. The median nadir platelet
count in those with significant thrombocytopenia was 10,000/uL (range 2,000
45,000/uL) versus 165,000/uL (50,000-429,000/uL) in those without (P < 0.001).
The median duration of significant thrombocytopenia in the first group was 10
days (1-35 days). Therapy during the period of significant thrombocytopenia
included prophylactic-dose low-molecular-weight heparin (LMWH) (47%), therapeutic
dose LMWH or heparin (30%), warfarin (2%), inferior vena cava filter (2%), and
observation (17%). Patients without thrombocytopenia were managed with the
standard of care therapy. At a median follow-up of more than 2 years, the risk of
clinically significant bleeding (11% vs 6%, P = 0.22) including major bleeding
(6% vs 2%) and clot progression or recurrence (21% vs 22%, P = 1.00) were similar
in patients with or without significant thrombocytopenia. In a multivariate
analysis, the risk of recurrence/progression (hazard ratio, HR 0.59, 95% CI 0.21
1.66, P = 0.31) and hemorrhage rate (HR 0.29, 95% CI 0.05-1.56, P = 0.15) did not
differ based on the presence of significant thrombocytopenia. Within the limits
of this retrospective study, cautious use of prophylactic-dose LMWH may be safe
in thrombocytopenic patients with hematologic malignancy-associated VTE. Am. J.
Hematol. 91:E468-E472, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27489983
TI - Elevated FGF 21 in myotonic dystrophy type 1 and mitochondrial diseases.
AB - INTRODUCTION: Human fibroblast growth factor 21 (FGF21) is a regulator of lipid
and glucose metabolism. It is expressed in skeletal muscle and may be a sensitive
and specific marker for mitochondrial diseases and other neuromuscular disorders.
METHODS: Serum FGF21 levels were determined in 71 human samples. Thirty patients
with mitochondrial disease, 16 patients with myotonic dystrophy type 1 (DM1), 5
patients with facioscapulohumeral dystrophy, and 20 healthy controls were
enrolled. Results Serum FGF21 levels were significantly elevated in patients with
progressive external ophthalmoplegia and DM1 compared with patients with
facioscapulohumeral dystrophy, other types of mitochondrial diseases, and
controls. In the mitochondrial disorder group, serum FGF21 levels were related to
the number of ragged blue fibers. Significant insulin resistance was found in DM1
that might be responsible for FGF21 elevation. Conclusions FGF21 elevation may be
associated with certain types of mitochondrial disease, and it is influenced by
insulin resistance. Muscle Nerve 55: 564-569, 2017.
PMID- 27489985
TI - Creative method of removing a giant fibrovascular polyp under endoscopic
guidance.
PMID- 27489984
TI - Endoscopic esophageal perforation extending upwards along the carotid arteries.
PMID- 27489987
TI - Bilateral adrenal tuberculosis diagnosed by endoscopic ultrasound-guided fine
needle aspiration cytology.
PMID- 27489988
TI - Augmented endoscopic resection for fibrotic or recurrent colonic polyps using an
ablation and cold avulsion technique.
PMID- 27489989
TI - A novel endoscopic technique for closure of a large esophageal perforation using
the clip-and-snare method with the prelooping technique.
PMID- 27489986
TI - Endoscopic septotomy of a magnet-induced neoseptum in a large mid-esophageal
diverticulum.
PMID- 27489991
TI - A large delayed esophageal perforation due to chicken bone impaction treated by
over-the-scope clipping.
PMID- 27489990
TI - Novel technique to relax the lower esophageal sphincter during challenging
peroral endoscopic myotomy (POEM).
PMID- 27489992
TI - Single-step endoscopic ultrasound-guided fluoroless gallbladder drainage using
the Axios lumen-apposing metal stent.
PMID- 27489993
TI - Submucosal tunneling endoscopic resection for leiomyomas located on opposite
esophageal walls: the role of a tortuous submucosal tunnel.
PMID- 27489994
TI - Closure of an intestinal perforation with an autologous fat plug in a man with
Crohn's disease.
PMID- 27489995
TI - A novel clip-assisted method for endoscopic removal of an impacted toothpick from
the colon.
PMID- 27489996
TI - Esophageal post-inflammatory polyposis in extensive and severe Crohn's disease
treated with anti-tumor necrosis factor alpha.
PMID- 27489997
TI - Quantitative assessment of a spatial multicriteria model for highly pathogenic
avian influenza H5N1 in Thailand, and application in Cambodia.
AB - The Highly Pathogenic Avian Influenza H5N1 (HPAI) virus is now considered endemic
in several Asian countries. In Cambodia, the virus has been circulating in the
poultry population since 2004, with a dramatic effect on farmers' livelihoods and
public health. In Thailand, surveillance and control are still important to
prevent any new H5N1 incursion. Risk mapping can contribute effectively to
disease surveillance and control systems, but is a very challenging task in the
absence of reliable disease data. In this work, we used spatial multicriteria
decision analysis (MCDA) to produce risk maps for HPAI H5N1 in poultry. We aimed
to i) evaluate the performance of the MCDA approach to predict areas suitable for
H5N1 based on a dataset from Thailand, comparing the predictive capacities of two
sources of a priori knowledge (literature and experts), and ii) apply the best
method to produce a risk map for H5N1 in poultry in Cambodia. Our results showed
that the expert-based model had a very high predictive capacity in Thailand (AUC
= 0.97). Applied in Cambodia, MCDA mapping made it possible to identify hotspots
suitable for HPAI H5N1 in the Tonle Sap watershed, around the cities of
Battambang and Kampong Cham, and along the Vietnamese border.
PMID- 27489999
TI - Arhgef1 negatively regulates neurite outgrowth through activation of RhoA
signaling pathways.
AB - Neurite outgrowth is essential for the establishment of functional neuronal
connections during brain development. This study identifies that Arhgef1 is
predominantly expressed in early neuronal developmental stages and negatively
regulates neurite outgrowth. Knockdown of Arhgef1 in either Neuro-2a cells or
primary cortical neurons leads to excess growth of neurites, whereas
overexpression of Arhgef1 prominently restricts neurite formation. Arhgef1
strongly activates RhoA activity while concomitantly inhibits Rac1 and Cdc42
activities. Pharmacological blockade of RhoA activity restores normal neurite
outgrowth in Arhgef1-overexpressed neurons. Importantly, Arhgef1 promotes F-actin
polymerization in neurons, probably through inhibiting the activity of the actin
depolymerizing factor cofilin. Collectively, these findings reveal that Arhgef1
functions as a negative regulator of neurite outgrowth through regulating RhoA
cofilin pathway and actin dynamics.
PMID- 27489998
TI - Oryzamides A-E, Cyclodepsipeptides from the Sponge-Derived Fungus Nigrospora
oryzae PF18.
AB - Three new cyclohexadepsipeptides, oryzamides A-C (1-3), two isolation artifacts,
oryzamides D (4) and E (5), and the known congener scopularide A (6), all
possessing a rare 3-hydroxy-4-methyldecanoic acid (HMDA) substructure, were
isolated from the mycelial extract of the sponge-derived fungus Nigrospora oryzae
PF18. Their planar structures were elucidated by spectroscopic analysis and
comparison with the literature data. The absolute configurations were determined
using the advanced Marfey's method and single-crystal X-ray diffraction analysis.
Among them, oryzamides D (4) and E (5) were a pair of diastereomers at the sulfur
atom of the l-methionine sulfoxide residue, which showcased the possible
separation of a pair of methionine sulfoxide diastereomers. The X-ray crystal
structure of scopularide A (6) was obtained for the first time, thereby
establishing its relative and absolute configuration at C-4 of the HMDA residue.
Oryzamides A-C (1-3) did not display cytotoxic, antibacterial, antiparasitic, and
NF-kappaB inhibitory activities.
PMID- 27490002
TI - Motion of tympanic membrane in guinea pig otitis media model measured by scanning
laser Doppler vibrometry.
AB - Otitis media (OM) is an inflammatory or infectious disease of the middle ear.
Acute otitis media (AOM) and otitis media with effusion (OME) are the two major
types of OM. However, the tympanic membrane (TM) motion differences induced by
AOM and OME have not been quantified in animal models in the literature. In this
study, the guinea pig AOM and OME models were created by transbullar injection of
Streptococcus pneumoniae type 3 and lipopolysaccharide, respectively. To explore
the effects of OM on the entire TM vibration, the measurements of full-field TM
motions were performed in the AOM, OME and untreated control ears by using
scanning laser Doppler vibrometry (SLDV). The results showed that both AOM and
OME generally reduced the displacement peak and produced the traveling-wave-like
motions at relatively low frequencies. Compared with the normal ear, OME resulted
in a significant change of the TM displacement mainly in the inferior portion of
the TM, and AOM significantly affected the surface motion across four quadrants.
The SLDV measurements provide more insight into sound-induced TM vibration in
diseased ears.
PMID- 27490004
TI - Disaster Management Response Guidelines for Departments of Orthopaedic Surgery.
AB - Complacency and lack of preparation are major barriers to an effective disaster
response. Leadership assignments and departmental organization for a response
should be outlined in advance. Response rehearsal and after-action reviews allow
for thoughtful change to a response plan. Hospital disaster alert notification
systems should be standardized and should be understood. Communication systems
used in a disaster should have redundancy. A department's response plan must be
integrated into the overall hospital plan. Large casualty volumes require
appropriate triage and resource allocation. Response provider emotional and
health support is an important consideration.
PMID- 27490003
TI - Drug-eluting balloon angioplasty versus uncoated balloon angioplasty for
peripheral arterial disease of the lower limbs.
AB - BACKGROUND: Atherosclerotic peripheral arterial disease (PAD) can lead to
disabling ischemia and limb loss. Treatment modalities have included risk factor
optimization through life-style modifications and medications, or operative
approaches using both open and minimally invasive techniques, such as balloon
angioplasty. Drug-eluting balloon (DEB) angioplasty has emerged as a promising
alternative to uncoated balloon angioplasty for the treatment of this difficult
disease process. By ballooning and coating the inside of atherosclerotic vessels
with cytotoxic agents, such as paclitaxel, cellular mechanisms responsible for
atherosclerosis and neointimal hyperplasia are inhibited and its devastating
complications are prevented or postponed. DEBs are considerably more expensive
than uncoated balloons, and their efficacy in improving patient outcomes is
unclear. OBJECTIVES: To assess the efficacy of drug-eluting balloons (DEBs)
compared with uncoated, nonstenting balloon angioplasty in people with
symptomatic lower-limb peripheral arterial disease (PAD). SEARCH METHODS: The
Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised
Register (last searched December 2015) and Cochrane Register of Studies (CRS)
(2015, Issue 11). The TSC searched trial databases for details of ongoing and
unpublished studies. SELECTION CRITERIA: We included all randomized controlled
trials that compared DEBs with uncoated, nonstenting balloon angioplasty for
intermittent claudication (IC) or critical limb ischemia (CLI). DATA COLLECTION
AND ANALYSIS: Two review authors (AK, TA) independently selected the appropriate
trials and performed data extraction, assessment of trial quality, and data
analysis. The senior review author (DKR) adjudicated any disagreements. MAIN
RESULTS: Eleven trials that randomized 1838 participants met the study inclusion
criteria. Seven of the trials included femoropopliteal arterial lesions, three
included tibial arterial lesions, and one included both. The trials were carried
out in Europe and in the USA and all used the taxane drug paclitaxel in the DEB
arm. Nine of the 11 trials were industry-sponsored. Four companies manufactured
the DEB devices (Bard, Bavaria Medizin, Biotronik, and Medtronic). The trials
examined both anatomic and clinical endpoints. There was heterogeneity in the
frequency of stent deployment and the type and duration of antiplatelet therapy
between trials. Using GRADE assessment criteria, the quality of the evidence
presented was moderate for the outcomes of target lesion revascularization and
change in Rutherford category, and high for amputation, primary vessel patency,
binary restenosis, death, and change in ankle-brachial index (ABI). Most
participants were followed up for 12 months, but one trial reported outcomes at
five years.There were better outcomes for DEBs for up to two years in primary
vessel patency (odds ratio (OR) 1.47, 95% confidence interval (CI) 0.22 to 9.57
at six months; OR 1.92, 95% CI 1.45 to 2.56 at 12 months; OR 3.51, 95% CI 2.26 to
5.46 at two years) and at six months and two years for late lumen loss (mean
difference (MD) -0.64 mm, 95% CI -1.00 to -0.28 at six months; MD -0.80 mm, 95%
CI -1.44 to -0.16 at two years). DEB were also superior to uncoated balloon
angioplasty for up to five years in target lesion revascularization (OR 0.28, 95%
CI 0.17 to 0.47 at six months; OR 0.40, 95% CI 0.31 to 0.51 at 12 months; OR
0.28, 95% CI 0.18 to 0.44 at two years; OR 0.21, 95% CI 0.09 to 0.51 at five
years) and binary restenosis rate (OR 0.44, 95% CI 0.29 to 0.67 at six months; OR
0.38, 95% CI 0.15 to 0.98 at 12 months; OR 0.26, 95% CI 0.10 to 0.66 at two
years; OR 0.12, 95% CI 0.05 to 0.30 at five years). There was no significant
difference between DEB and uncoated angioplasty in amputation, death, change in
ABI, change in Rutherford category and quality of life (QoL) scores, or
functional walking ability, although none of the trials were powered to detect a
significant difference in these clinical endpoints. We carried out two subgroup
analyses to examine outcomes in femoropopliteal and tibial interventions as well
as in people with CLI (4 or greater Rutherford class), and showed no advantage
for DEBs in tibial vessels at six and 12 months compared with uncoated balloon
angioplasty. There was also no advantage for DEBs in CLI compared with uncoated
balloon angioplasty at 12 months. AUTHORS' CONCLUSIONS: Based on a meta-analysis
of 11 trials with 1838 participants, there is evidence of an advantage for DEBs
compared with uncoated balloon angioplasty in several anatomic endpoints such as
primary vessel patency (high-quality evidence), binary restenosis rate (moderate
quality evidence), and target lesion revascularization (low-quality evidence) for
up to 12 months. Conversely, there is no evidence of an advantage for DEBs in
clinical endpoints such as amputation, death, or change in ABI, or change in
Rutherford category during 12 months' follow-up. Well-designed randomized trials
with long-term follow-up are needed to compare DEBs with uncoated balloon
angioplasties adequately for both anatomic and clinical study endpoints before
the widespread use of this expensive technology can be justified.
PMID- 27490005
TI - Treatment of Proximal Humeral Fractures: A Critical Analysis Review.
AB - There is substantial variability in the treatment of proximal humeral fractures
because of classification systems with poor interobserver reliability, rapid
advances in technology (e.g., anatomically designed locking plates and reverse
shoulder arthroplasty), and limited Level-I and II evidence for best treatments
based on fracture patterns and physiological age. Almost three-quarters of
proximal humeral fractures can be treated nonoperatively with good functional
results as nearly 50% are nondisplaced or Neer one-part fractures. Another
quarter occur in infirm patients or are characterized by fracture patterns that
reliably heal well with minimal complications. Displaced fractures in
physiologically young patients should preferentially be treated with open
reduction and internal fixation (ORIF) as functional outcomes are generally good
and anatomical restoration can improve the results of subsequent arthroplasty, if
needed. Improved results with fixation have been reported in association with the
use of bone substitutes, fibular strut allografts, and inferior head-supporting
calcar screws to prevent humeral head displacement and screw perforation. A
number of recent trials have brought into question the advantage of both ORIF and
hemiarthroplasty over nonoperative treatment for patients over the age of sixty
years who have three and four-part fractures without dislocations. Reverse
shoulder arthroplasty initially showed varied results for the treatment of
irreparable fractures in healthy older patients, but recent Level-I and II
studies have shown an advantage over hemiarthroplasty. Medium and long-term data
are still needed.
PMID- 27490006
TI - Wrong-Site Surgery in Orthopaedics: Prevalence, Risk Factors, and Strategies for
Prevention.
AB - The incidence of wrong-site surgery in orthopaedics is unknown. This is due to a
lack of data regarding the exact numbers of surgical procedures performed and a
lack of a uniform mandatory error reporting infrastructure. Twenty-one percent of
hand surgeons, 50% of spinal surgeons, and 8.3% of knee surgeons surveyed have
reported performing at least one wrong-site surgery during their career. Every
orthopaedic surgeon, no matter his or her orthopaedic subspecialty, is at risk
for completing a wrong-site surgery during his or her career. Prevention of wrong
site surgery should remain a priority for the orthopaedic community. Surgeon
leadership, commitment, and vigilance are critical to improve patient safety by
ensuring that validated safety processes are used in all orthopaedic settings
including effective surgical team communication, checklists, and routine
collection and analysis of quality and safety data.
PMID- 27490008
TI - Biological Risk Factors for Nonunion of Bone Fracture.
AB - Many risk factors for fracture nonunion are well supported in the orthopaedic
literature, including location of the fracture site, surgical treatment, bone
displacement, type of fixation, treatment delay, comminution, inadequate
treatment, and wound infection. However, evidence from a systematic review
suggests that patient-related or biological causes of nonunion may not be as well
understood. Understanding the biological causes of nonunion is important for
several reasons. Risk factors might identify patients prone to nonunion who could
benefit from more aggressive intervention, and a clear idea of nonunion risk
could be important when choosing between competing therapeutic options. Risk
factors also can inform the design of clinical trials and clarify patient
inclusion and exclusion criteria, so that small studies can yield more definitive
answers. Finally, an understanding of patient risk profiles may enable clinicians
to counsel patients more effectively and to set appropriate expectations for
success. Patient age appears to be a strong risk factor for nonunion in some
bones, a weak risk factor for nonunion in other bones, and perhaps not a
significant risk factor for nonunion in certain bones. This observation suggests
that there can be substantial bone-to-bone variation in nonunion risk. Age also
may be a surrogate for the prevalence of risk factors that potentially increase
with age, such as smoking, diabetes, obesity, or nonsteroidal anti-inflammatory
drug (NSAID) use. Smoking has been replicated as a risk factor for nonunion only
in retrospective studies involving the humerus and tibia. Smoking appears to have
an important effect on nonunion, yet the incremental risk may be rather small,
except in context with additional risk factors. Diabetes has been confirmed as a
risk factor for nonunion only in retrospective studies involving the foot and
ankle. Nonunion risk from diabetes alone may be small and the context of
additional risk factors crucial; this could account for why it has been so
difficult to predict nonunion in the individual patient. Prediction of fracture
nonunion in the individual patient is a difficult problem. Fracture nonunion may
be influenced by complex interactions between biological and surgical risk
factors, and the nonunion rate varies from bone to bone. A randomized clinical
trial may not appropriately control for all potential correlates and confounders
and may require impractical sample sizes. A large claims-based study of real
world fracture-healing outcomes is needed to provide guidance for randomized
clinical trials that can test risk factors more rigorously.
PMID- 27490007
TI - Rehabilitation Following Anterior Cruciate Ligament Tears in Children: A
Systematic Review.
AB - BACKGROUND: Anterior cruciate ligament (ACL) tears are increasingly prevalent in
the pediatric population. ACL rehabilitation is an essential component of
recovery following injury and reconstruction, yet there are few explicit
descriptions of pediatric-specific ACL rehabilitation protocols in the
literature, especially in the context of varying treatment interventions. Our aim
was to systematically review the literature on rehabilitation following ACL tears
in children in order to describe common principles among different treatment
options and areas of future research. METHODS: Using PRISMA (Preferred Reporting
Items for Systematic Reviews and Meta-Analyses) guidelines, we performed a
systematic review of the PubMed, EMBASE, and Cochrane databases (for the past
five years) to identify detailed rehabilitation protocols described in the
pediatric population following ACL rupture. When available, the following aspects
of rehabilitation were extracted: "prehabilitation" (exercises prior to surgery),
bracing, weight-bearing status, range of motion, strength, modalities (ice, heat,
electrical stimulation, etc.), plyometrics/proprioceptive exercises, return-to
sport criteria, and suggested ACL injury-prevention programs. RESULTS: Two
hundred and two unique articles were identified. Twenty-seven articles meeting
inclusion criteria with extractible rehabilitation data were included. A table,
categorized by differing orthopaedic intervention, was designed to detail the
components and duration of the different aspects of rehabilitation. While there
are substantial differences across protocols, several trends emerged,
particularly regarding weight-bearing, bracing, range of motion, and strength
training. Interestingly, we found that many current protocols are based on time
frame alone rather than on functional milestones; of the fourteen unique articles
that addressed return-to-sport criteria by specific orthopaedic intervention,
seven were based on temporal progression whereas seven also involved achievement
of physical milestones. In addition, only three of the eight articles that
mentioned a future ACL injury-prevention plan described a formal prevention
program. CONCLUSION: We systematically identified, and subsequently outlined and
compared, the current trends of the various components of pediatric-specific ACL
rehabilitation protocols, categorized by orthopaedic intervention. Several
protocols are based on time frames rather than milestones achieved, with newer
protocols involving milestone-based progression. Newer protocols are also
incorporating formal prevention programs. Just as skeletally immature patients
require unique methods of operative fixation, so too do they require catered
rehabilitation protocols. To effectively prevent re-rupture or contralateral
injury, future research should focus on prospectively evaluating each component
of the rehabilitation protocols described and return-to-sport criteria for young
patients.
PMID- 27490001
TI - Evidence of activity-dependent plasticity in the dorsal cochlear nucleus, in
vivo, induced by brief sound exposure.
AB - The purpose of the present study was to investigate the immediate effects of
acute exposure to intense sound on spontaneous and stimulus-driven activity in
the dorsal cochlear nucleus (DCN). We examined the levels of multi- and single
unit spontaneous activity before and immediately following brief exposure (2 min)
to tones at levels of either 109 or 85 dB SPL. Exposure frequency was selected to
either correspond to the units' best frequency (BF) or fall within the borders of
its inhibitory side band. The results demonstrate that these exposure conditions
caused significant alterations in spontaneous activity and responses to BF tones.
The induced changes have a fast onset (minutes) and are persistent for durations
of at least 20 min. The directions of the change were found to depend on the
frequency of exposure relative to BF. Transient decreases followed by more
sustained increases in spontaneous activity were induced when the exposure
frequency was at or near the units' BF, while sustained decreases of activity
resulted when the exposure frequency fell inside the inhibitory side band. Follow
up studies at the single unit level revealed that the observed activity changes
were found on unit types having properties which have previously been found to
represent fusiform cells. The changes in spontaneous activity occurred despite
only minor changes in response thresholds. Noteworthy changes also occurred in
the strength of responses to BF tones, although these changes tended to be in the
direction opposite those of the spontaneous rate changes. We discuss the possible
role of activity-dependent plasticity as a mechanism underlying the rapid
emergence of increased spontaneous activity after tone exposure and suggest that
these changes may represent a neural correlate of acute noise-induced tinnitus.
PMID- 27490010
TI - Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular
Benzoin Reaction.
AB - The strategy of stereodivergent reactions on racemic mixtures (stereodivergent
RRM) was employed for the first time in intramolecular benzoin reactions and led
to the rapid access of chromanones/flavanones with two consecutive stereocenters.
The easily separable stereoisomers of the products were obtained with moderate to
excellent enantioselectivities in a single step. Catechol type additives proved
crucial in achieving the desired diastereo- and enantioselectivities.
PMID- 27490015
TI - Treatment of Foot Deformities in Arthrogryposis Multiplex Congenita.
PMID- 27490014
TI - Assessment and Treatment of Extensor Carpi Ulnaris Tendon Pathology: A Critical
Analysis Review.
PMID- 27490016
TI - Antifibrinolytic Therapy for Perioperative Blood Conservation in Lower-Extremity
Primary Total Joint Arthroplasty.
PMID- 27490009
TI - Morphological and dynamic contrast enhanced MR imaging features for the
differentiation of chordoma and giant cell tumors in the Axial Skeleton.
AB - PURPOSE: To characterize the morphological and dynamic-contrast-enhanced (DCE)
MRI features of chordoma and giant cell tumor (GCT) of bone occurring in the
axial skeleton. MATERIALS AND METHODS: A total of 13 patients with chordoma and
26 patients with GCT who received conventional T1, T2, and DCE-MRI on 3 Tesla MR
scanners were retrospectively identified and analyzed. Two radiologists evaluated
morphological features independently, including the lesion location, expansile
bone changes, vertebral compression, presence of paraspinal soft tissue mass,
fibrous septa, and the signal intensity on T1WI and T2WI. The inter-observer
agreement was evaluated by kappa test. The DCE kinetics was measured to obtain
the initial area under curve (IAUC) and the wash-out slope; also the two
compartmental pharmacokinetic model was applied to obtain Ktrans and kep . The
diagnostic accuracy was evaluated by CHAID decision tree and ROC analysis.
RESULTS: Chordomas were more likely to show soft tissue mass than GCTs (13/13 =
100% versus 15/26 = 58%; P = 0.007), as well as fibrous septa (9/13 = 69% versus
0; P < 0.001). In decision tree analysis, presence of fibrous septa and lesion
location yield 31/39 = 79% accuracy. The DCE-MRI pharmacokinetic parameters
Ktrans and kep of GCTs were significantly higher than those of chordomas, 0.13 +/
0.65 versus 0.06 +/- 0.04 (1/min) for Ktrans , 0.62 +/- 0.22 versus 0.17 +/-
0.12 (1/min) for kep , P < 0.001 for both. If using kep = 0.43/min as the cut-off
value, it achieved 100% sensitivity and 92% specificity to differentiate chordoma
from GCT, with an overall accuracy of 37/39 = 95%. The IAUC was highly correlated
with Ktrans (r = 0.94), and the slope was highly correlated with kep (r = 0.95).
CONCLUSION: Several morphological features were significantly different between
chordoma and GCT, but their diagnostic performance was inferior to that of DCE
MRI. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:1068-1075.
PMID- 27490017
TI - Classification of Advanced Human Cancers Based on Tumor Immunity in the
MicroEnvironment (TIME) for Cancer Immunotherapy.
PMID- 27490013
TI - Effects of Antibiotic Prophylaxis in Patients with Open Fracture of the
Extremities: A Systematic Review of Randomized Controlled Trials.
AB - BACKGROUND: The purpose of the present study was to perform a systematic review
and meta-analysis of the use of alternative antibiotic regimens-including (A)
antibiotic prophylaxis versus no prophylaxis, (B) longer versus shorter duration
of antibiotic prophylaxis, and (C) alternative drugs-for patients with open
fracture of the extremities. METHODS: Data sources included CINAHL, EMBASE,
MEDLINE, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the
Cochrane database of systematic reviews from 1965 to December 2013. All
randomized controlled trials comparing the effectiveness of antibiotic
prophylaxis in patients with open fracture of the extremities were eligible.
RESULTS: We identified 329 potentially eligible articles, of which seventeen
proved to be eligible. In four randomized controlled trials involving 472
patients, we found a significantly lower infection rate in patients receiving
antibiotic prophylaxis compared with those not receiving antibiotic prophylaxis
(risk ratio = 0.37 [95% confidence interval, 0.21 to 0.66]; absolute risk
reduction = 9.6% [95% confidence interval, 5.2% to 12.1%]). In three studies
involving 1104 patients, we found no difference in the infection rate when a
longer duration of antibiotics (three to five days) was compared with a shorter
duration (one day) (risk ratio = 0.97; 95% confidence interval, 0.69 to 1.37).
Confidence in the estimates for both questions was low to moderate. Individual
comparisons of alternative drugs yielded estimates warranting only low to very
low confidence. CONCLUSIONS: Results of randomized controlled trials performed to
date provide evidence that antibiotic prophylaxis reduces subsequent infection
and that courses as short as one day are as effective as courses of three to five
days, although the evidence warrants only low to moderate confidence. Given
current practice, a large, multicenter, low risk of bias, randomized controlled
trial enrolling representative populations and addressing the duration of
antibiotics may be the next optimum step in investigation. LEVEL OF EVIDENCE:
Therapeutic Level I. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 27490011
TI - Comparative Study of Charge-Assisted Hydrogen- and Halogen-Bonding Capabilities
in Solution of Two-Armed Imidazolium Receptors toward Oxoanions.
AB - Two-armed imidazolium-based anion receptors have been prepared. The central 2,7
disubstituted naphthalene ring features two photoactive anthracene end-capped
side arms with central 2-bromoimidazolium or hydrogen-bonding imidazolium
receptors. Combined emission and (1)H and (31)P NMR studies carried out in the
presence of a wide variety of anions reveal that only HP2O7(3-), H2PO4(-), SO4(2
), and F(-) anions promoted noticeable changes. The halogen receptor 6(2+).2PF6(
) acts as a selective fluorescent molecular sensor for H2PO4(-) anions, since
only this anion promotes the appearance of the anthracene excimer emission band,
whereas it remains unchanged in the presence of the other tested anions. In
addition this halogen receptor behaves as a chemodosimeter toward HP2O7(3-)
anion, through its transformation into the corresponding bis-imidazolone after
debromination by the action of the basic anion. The association constant values
of the halogen-bonding complexes in a competitive solvent CD3CN/MeOD (8/2)
mixture with H2PO4(-) and SO4(2-) anions are higher than those found for the
hydrogen-bonding counterpart. In contrast, in the less competitive CH3CN solvent
higher binding affinity for anions corresponds to the hydrogen-bonding receptor
7(2+).2PF6(-). In addition, the receptor 6(2+).2PF6(-) represents a useful
alternative as an imaging agent in living cells in a wide range of emission
wavelengths.
PMID- 27490020
TI - Clinical outcomes and safety of distal biceps repair using a modified entry
point.
AB - BACKGROUND: The purpose of this study is to determine the safety of a one
incision technique for distal biceps repair with modified repair entry point in
regards to the distance from the posterior interosseous nerve (PIN). Secondly, we
present the clinical results of patients having undergone this procedure.
METHODS: Ten cadaveric specimens were dissected to reveal the radial tuberosity.
Two 1.6-mm guidewires were inserted into the radial tuberosity, one centrally,
and one 5-mm more proximal. Both guidewires penetrated the dorsal cortex, and
posterior dissection revealed their exit points. The distance from the PIN and
each wire was determined using a vernier calliper. The functional outcomes of 10
patients' post repair were reviewed. Performance was determined using strength
and range of motion (ROM) measurements. Functional impairment was assessed using
the disability of the arm, shoulder and hand outcome measure (DASH score). The
uninjured side was used as a control. RESULTS: The mean distance from the centre
of the radial tuberosity to the PIN was 7.33 mm with a centrally placed wire,
compared with 10.92 mm when measuring from the proximal guidewire (P < 0.05).
Supination and flexion strengths were 83 and 90% of the uninjured side,
respectively. There was a mean of 1.5 degrees loss of flexion and 0 degrees
loss of extension. Loss of pronation and supination ROM were 0.5 degrees and 4.5
degrees on average, respectively. Average DASH score was 6.3. CONCLUSION: We
recommend a 5-mm more proximal entry point for insertion of the guidewire during
distal biceps repair. This poses less risk to the PIN without significant
functional impairment. Our outcomes are comparable with those reported in the
literature.
PMID- 27490012
TI - Hamstring Injuries in Athletes: Diagnosis and Treatment.
PMID- 27490023
TI - Design, synthesis and structure-activity relationships of novel 4
phenoxyquinoline derivatives containing 1,2,4-triazolone moiety as c-Met kinase
inhibitors.
AB - A series of novel 4-phenoxyquinoline derivatives containing 1,2,4-triazolone
moiety were synthesized and evaluated for their in vitro cytotoxic activity
against four cancer cell lines (HT-29, H460, A549 and MKN-45). Most of the
compounds exhibited moderate-to-significant cytotoxicity. Compounds 33, 37, 39,
44, 46, 47, 53, 55, 61, 64 and 66 were further examined for their inhibitory
activity against c-Met kinase. The most promising compound 47 (with c-Met IC50
value of 1.57 nM) showed remarkable cytotoxicity against HT-29, H460, A549 and
MKN-45 cell lines with IC50 values of 0.08 MUM, 0.14 MUM, 0.11 MUM and 0.031 MUM,
respectively, and thus it was 1.1- to 2.3- fold more potent than foretinib. Their
preliminary structure-activity relationships (SARs) studies indicate that
electron-withdrawing groups on the terminal phenyl rings are beneficial for
improving the antitumor activity.
PMID- 27490024
TI - Synthesis and antiproliferative mechanism of action of pyrrolo[3',2':6,7]
cyclohepta[1,2-d]pyrimidin-2-amines as singlet oxygen photosensitizers.
AB - A new series of pyrrolo[3',2':6,7]cyclohepta[1,2-d]pyrimidin-2-amines, was
conveniently prepared using a versatile and high yielding multistep sequence. A
good number of derivatives was obtained and the cellular photocytotoxicity was
evaluated in vitro against three different human tumor cell lines with EC50 (0.08
4.96 MUM) values reaching the nanomolar level. Selected compounds were
investigated by laser flash photolysis. The most photocytotoxic derivative,
exhibiting a fairly long-lived triplet state (tau ~ 7 MUs) and absorbance in the
UV-Vis, was tested in the photo-oxidations of 9,10-anthracenedipropionic acid
(ADPA) by singlet oxygen. The photosentizing properties are responsible for the
compounds' ability to photoinduce massive cell death with involvement of
mitochondria.
PMID- 27490025
TI - Pyrrolidinone and pyrrolidine derivatives: Evaluation as inhibitors of InhA and
Mycobacterium tuberculosis.
AB - A series of GEQ analogues bearing pyrrolidinone or pyrrolidine cores were
synthesized and evaluated against InhA, essential target for Mycobacterium
tuberculosis (M.tb) survival. The compounds were also evaluated against M.tb
H37Rv growth. Interestingly, some of the compounds, not efficient as InhA
inhibitors, are active against M.tb with MICs up to 1.4 MUM. In particular,
compound 4b was screened with different M.tb mutated strains in order to identify
the cellular target, but without success, suggesting a new possible mode of
action.
PMID- 27490022
TI - Design, synthesis and biological evaluation of novel cholesteryl ester transfer
protein inhibitors bearing a cycloalkene scaffold.
AB - Cholesteryl ester transfer protein (CETP) is a potential target for
cardiovascular disease therapy as inhibition of CETP leads to increased HDL-C in
humans. Based on the structure of Merck's biphenyl CETP inhibitor, we designed
novel N,N-substituted-cycloalkenyl-methylamine scaffold derivatives by utilizing
core replacement and conformational restriction strategies. Consequently, twenty
eight compounds were synthesized and evaluated for their inhibitory activity
against CETP. Their preliminary structure-activity relationships (SARs) studies
indicate that polar substituents were tolerated in moiety A and hydrophobic alkyl
groups at the 5-position of cyclohexene were critical for potency. Among them,
compound 17a, bearing an N-(5-pyrazolyl-pyrimidin-2-yl)-cycloalkenyl- methylamine
scaffold, exhibited excellent CETP inhibitory activity (IC50 = 0.07 MUM) in
vitro. Furthermore, it showed an acceptable pharmacokinetic profile in S-D rats
and efficient HDL-C increase in high-fat fed hamsters.
PMID- 27490019
TI - Rationally Designed CeNP@MnMoS4 Core-Shell Nanoparticles for Modulating Multiple
Facets of Alzheimer's Disease.
AB - Alzheimer's disease (AD) is a complicated multifactorial syndrome. Lessons have
been learned through failed clinical trials that targeting multiple key pathways
of the AD pathogenesis is necessary to halt the disease progression. Here, we
construct core-shell nanoparticles (CeNP@MnMoS4 ) targeting multiple key pathways
of the AD pathogenesis, including elimination of toxic metal ions, decrease of
oxidative stress, and promotion of neurite outgrowth. The SOD activity and copper
removal capacity of CeNP@MnMoS4 -n (n represents the number of layers of MnMoS4 ,
n=1-5) was investigated in vitro. We found that CeNP@MnMoS4 -3 made an excellent
balance between SOD activity and copper removal capacity. The effect of
CeNP@MnMoS4 -3 on Cu(2+) -induced Abeta aggregation was studied by gel
electrophoresis, transmission electron microscope (TEM), and atomic force
microscopy (AFM). Compared with MnMoS4 or CeNP alone, a synergistic effect was
observed. Moreover, CeNP@MnMoS4 -3 promoted neurite outgrowth in a dose-dependent
manner. Taken together, the results reported in this work show the potential of
new multifunctional core-shell nanoparticles as AD therapeutics.
PMID- 27490030
TI - Analysis of the Resistance of Hepatitis C Virus NS5B Polymerase Inhibitors via
Docking and Molecular Dynamics Simulation.
AB - In this work, we examined how known single point mutations (P495S, P495L, P495A,
P496A, P496S and V499A) in Hepatitis C virus NS5B polymerase influence the
binding of benzimidazole-5-carboxamide derivatives which are potent NS5B
inhibitors. Docking and molecular dynamics simulations were performed to analyze
the binding of the inhibitors to the wild-type and mutant enzymes. Binding free
energy calculations (MM-GB/SA method) and analyzing the decomposed binding free
energy of individual residues were able to explain the differences in the
inhibitory potency of the compounds at wild-type and mutant enzymes and hence
account for the appearance of resistance of mutant enzymes to the studied
inhibitors. The obtained results were found to be in agreement with the known
experimental data.
PMID- 27490027
TI - Patient independent representation of the detailed cardiac ventricular anatomy.
AB - Reparameterization of surfaces is a widely used tool in computer graphics known
mostly from the remeshing algorithms. Recently, the surface reparameterization
techniques started to gain popularity in the field of medical imaging, but mostly
for convenient 2D visualization of the information initially represented on 3D
surfaces (e.g. continuous bulls-eye plot). However, by consistently mapping the
3D information to the same 2D domain, surface reparameterization techniques allow
us to put into correspondence anatomical shapes of inherently different geometry.
In this paper, we propose a method for anatomical parameterization of cardiac
ventricular anatomies that include myocardium, trabeculations, tendons and
papillary muscles. The proposed method utilizes a quasi-conformal flattening of
the myocardial surfaces of the left and right cardiac ventricles and extending it
to cover the interior of the cavities using the local coordinates given by the
solution of the Laplace's equation. Subsequently, we define a geometry
independent representation for the detailed cardiac left and right ventricular
anatomies that can be used for convenient visualization and statistical analysis
of the trabeculations in a population. Lastly we show how it can be used for
mapping the detailed cardiac anatomy between different hearts, which is of
considerable interest for detailed cardiac computational models or shape atlases.
PMID- 27490029
TI - Importance of arterial stiffness in predicting cardiovascular events.
AB - INTRODUCTION: Cardiovascular events represent an important cause of morbidity and
mortality in the entire population. Arterial stiffness is currently considered
one of the most important risk factors for the development of cardiovascular
events. The gold-standard for evaluating arterial stiffness is pulse wave
velocity (PWV). Recent studies have demonstrated that PWV is an independent risk
factor regarding the development of cardiovascular events, especially in certain
categories of patients. MATERIAL AND METHODS: The development of cardiovascular
events was assessed in 174 patients admitted in the Center of Internal Medicine,
Fundeni Clinical Institute, between January 2011 - May 2012. Arterial stiffness
was evaluated by measuring PWV using the Sphygmocor system (AtCor, Australia),
which is based on the principle of applanation tonometry. The patients were
monitored for the development of cardiovascular events (ischemic heart disease,
heart failure, stroke, acute myocardial infarction) and for death of
cardiovascular cause, over a median period of 51.5 months (43-60 months).
RESULTS: Of the 174 patients, 81 (46.6%) were women and 93 (53.4%) were men. Mean
age was 55.96 years. 93 of the 174 patients had chronic kidney failure in
different stages (47.3% in stage V). Regarding PWV in the patient group, we
obtained a mean score of 9.382. We observed a significant difference regarding
the PWV level only for acute myocardial infarction and death between patients who
developed these events and those who did not. CONCLUSIONS: Our study demonstrates
that PWV increase can be positively associated with the occurrence of
cardiovascular events, particularly in certain groups of patients.
PMID- 27490034
TI - Improving AutoDock Vina Using Random Forest: The Growing Accuracy of Binding
Affinity Prediction by the Effective Exploitation of Larger Data Sets.
AB - There is a growing body of evidence showing that machine learning regression
results in more accurate structure-based prediction of protein-ligand binding
affinity. Docking methods that aim at optimizing the affinity of ligands for a
target rely on how accurate their predicted ranking is. However, despite their
proven advantages, machine-learning scoring functions are still not widely
applied. This seems to be due to insufficient understanding of their properties
and the lack of user-friendly software implementing them. Here we present a study
where the accuracy of AutoDock Vina, arguably the most commonly-used docking
software, is strongly improved by following a machine learning approach. We also
analyse the factors that are responsible for this improvement and their
generality. Most importantly, with the help of a proposed benchmark, we
demonstrate that this improvement will be larger as more data becomes available
for training Random Forest models, as regression models implying additive
functional forms do not improve with more training data. We discuss how the
latter opens the door to new opportunities in scoring function development. In
order to facilitate the translation of this advance to enhance structure-based
molecular design, we provide software to directly re-score Vina-generated poses
and thus strongly improve their predicted binding affinity. The software is
available at http://istar.cse.cuhk.edu.hk/rf-score-3.tgz and http://crcm.
marseille.inserm.fr/fileadmin/rf-score-3.tgz.
PMID- 27490032
TI - Quality Assessment of Predicted Protein Models Using Energies Calculated by the
Fragment Molecular Orbital Method.
AB - Protein structure prediction directly from sequences is a very challenging
problem in computational biology. One of the most successful approaches employs
stochastic conformational sampling to search an empirically derived energy
function landscape for the global energy minimum state. Due to the errors in the
empirically derived energy function, the lowest energy conformation may not be
the best model. We have evaluated the use of energy calculated by the fragment
molecular orbital method (FMO energy) to assess the quality of predicted models
and its ability to identify the best model among an ensemble of predicted models.
The fragment molecular orbital method implemented in GAMESS was used to calculate
the FMO energy of predicted models. When tested on eight protein targets, we
found that the model ranking based on FMO energies is better than that based on
empirically derived energies when there is sufficient diversity among these
models. This model diversity can be estimated prior to the FMO energy
calculations. Our result demonstrates that the FMO energy calculated by the
fragment molecular orbital method is a practical and promising measure for the
assessment of protein model quality and the selection of the best protein model
among many generated.
PMID- 27490031
TI - Molecular Determinants for the Binding Mode of Alkylphosphocholines in the C2
Domain of PKCalpha.
AB - Alkylphosphocholines (APCs) and alkyl-lysophosphocholines (ALPs) are
antineoplastic agents that interfere with cellular membranes and signaling
proteins. Protein kinase Calpha (PKCalpha) is a signaling protein composed by
catalytic (C3, C4) and regulatory domains (C1, C2). The C2 needs calcium (Ca(2+)
) and phosphatidylserine (PS) for activation. Miltefosine inhibits PKCalpha
competitively with regard to PS and non-competitively with regard to Ca(2+) ,
however, the mechanism of action is unknown. We employed molecular docking,
molecular dynamics and chemometric methods to verify how 7 APCs and ALPs
derivatives and PS interact with the C2 domain. All ligands except PS were
grouped in 2 clusters according to their interactions inside the enzyme. The
findings showed that PS's phosphoryl oxygens interact with Ca(2+) , the serine
moiety interacts with Asn189, and the carbonyl oxygen of the alkylic chain
interacts with Arg249 and Thr251. On the other hand, ligands' phosphoryl oxygens
interact with Asn189, Arg249, Thr250, and one water molecule instead of Ca(2+) .
Because of the different binding mode, we hypothesize that the ligands cause
conformational changes in the calcium binding region. Moreover, the packing
mismatch between bilayer-forming lipids and ALP/APC chain impedes the C2 domain
from docking to the internal leaflet of cellular membranes, interrupting PKCalpha
activation.
PMID- 27490026
TI - Surface Passivation for Reliable Measurement of Bulk Electronic Properties of
Heterojunction Devices.
AB - Quantum efficiency measurements of state of the art Cu(In,Ga)Se2 (CIGS) thin film
solar cells reveal current losses in the near infrared spectral region. These
losses can be ascribed to inadequate optical absorption or poor collection of
photogenerated charge carriers. Insight on the limiting mechanism is crucial for
the development of more efficient devices. The electron beam induced current
measurement technique applied on device cross-sections promises an experimental
access to depth resolved information about the charge carrier collection
probability. Here, this technique is used to show that charge carrier collection
in CIGS deposited by multistage co-evaporation at low temperature is efficient
over the optically active region and collection losses are minor as compared to
the optical ones. Implications on the favorable absorber design are discussed.
Furthermore, it is observed that the measurement is strongly affected by cross
section surface recombination and an accurate determination of the collection
efficiency is not possible. Therefore it is proposed and shown that the use of an
Al2 O3 layer deposited onto the cleaved cross-section significantly improves the
accuracy of the measurement by reducing the surface recombination. A model for
the passivation mechanism is presented and the passivation concept is extended to
other solar cell technologies such as CdTe and Cu2 (Zn,Sn)(S,Se)4 .
PMID- 27490033
TI - Computational Investigation and Experimental Validation of Crizotinib Resistance
Conferred by C1156Y Mutant Anaplastic Lymphoma Kinase.
AB - Crizotinib is an anticancer drug approved by FDA for the treatment of non-small
cell lung cancer (NSCLC). The main target for crizotinib was anaplastic lymphoma
kinase (ALK). However, evidences available indicate that C1156Y mutation in ALK
confers resistance to crizotinib. Unfortunately, how mutation actually confers
drug resistance is not well understood. Hence, in the present study computational
approaches have been employed alongside KINOMEscan profiling technique to reveal
the mechanism behind crizotinib resistance in ALK at a molecular level. The
results of our analysis indicate that C1156Y mutation alters the conformation of
the ALK binding pocket residues which results in a marked decrease in hydrogen
bond interactions between crizotinib and ALK. This indicates that hydrogen
bonding was a crucial effector of decreased binding affinity. Interestingly, the
docking study also indicates that C1156Y mutation increases the affinity for ATP.
Finally, our analysis theoretically suggests that M-1199 is a key residue
responsible for the ALK drug selectivity. We certainly believe that these results
may be immense importance for the molecular level understanding of crizotinib
resistance pattern and also for designing a potential drug molecule for the
treatment of lung cancer in the near future.
PMID- 27490035
TI - Determination of Meta-Parameters for Support Vector Machine Linear Combinations.
AB - Support vector machines (SVMs) are among the most popular machine learning
methods for compound classification and other chemoinformatics tasks such as, for
example, the prediction of ligand-target pairs or compound activity profiles.
Depending on the specific applications, different SVM strategies can be used. For
example, in the context of potency-directed virtual screening, linear
combinations of multiple SVM models have been shown to enrich database selection
sets with potent compounds compared to individual models. An open question
concerning the use of SVM linear combinations (SVM-LCs) is how to best weight the
models on a relative scale. Typically, linear weights are subjectively set.
Herein, preferred weighting factors for SVM-LC were systematically determined.
Therefore, weights were treated as meta-parameters and optimized by machine
learning to enrich data set rankings with highly active compounds. The meta
parameter approach has been applied to 10 screening data sets and found to
further improve SVM performance over other SVM-LCs and support vector regression
(SVR) models. The results show that optimal weights depend on data set
characteristics and chosen molecular representations. In addition, individual
models often do not contribute to the performance of SVM-LCs. Taken together,
these findings emphasize the need for systematic meta-parameter estimation.
PMID- 27490037
TI - Design of Novel Mycobacterium tuberculosis Pantothenate Synthetase Inhibitors:
Virtual Screening, Synthesis and In Vitro Biological Activities.
AB - Pantothenate synthetase (PS) enzyme involved in the pantothenate biosynthetic
pathway is essential for the virulence and persistent growth of Mycobacterium
tuberculosis (MTB). It is encoded by the panC gene, and has become an appropriate
target for developing new therapeutics for tuberculosis. Here we report new
inhibitors active against MTB PS developed using energy based pharmacophore
modelling of the available protein?inhibitor complex (3IVX) and virtual screening
of a large commercial library. The e-pharmacophore model consisted of a ring
aromatic (R), negative ionizable (N) and acceptor (A) sites. Compounds 5 and 10
emerged as promising hits with IC50 s 2.18 uM and 6.63 uM respectively. Further
structural optimization was attempted to optimize lead 10 using medicinal
chemistry approach and six compounds were found to exhibit better enzyme
inhibition compared to parent compound lead 10 (<6 uM).
PMID- 27490036
TI - Hit Expansion from Screening Data Based upon Conditional Probabilities of
Activity Derived from SAR Matrices.
AB - A new methodology for activity prediction of compounds from SAR matrices is
introduced that is based upon conditional probabilities of activity. The approach
has low computational complexity, is primarily designed for hit expansion from
biological screening data, and accurately predicts both active and inactive
compounds. Its performance is comparable to state-of-the-art machine learning
methods such as support vector machines or Bayesian classification. Matrix-based
activity prediction of virtual compounds further extends the spectrum of
computational methods for compound design.
PMID- 27490028
TI - Amalgamated Reference Data for Size-Adjusted Bone Densitometry Measurements in
3598 Children and Young Adults-the ALPHABET Study.
AB - The increasing use of dual-energy X-ray absorptiometry (DXA) in children has led
to the need for robust reference data for interpretation of scans in daily
clinical practice. Such data need to be representative of the population being
studied and be "future-proofed" to software and hardware upgrades. The aim was to
combine all available pediatric DXA reference data from seven UK centers to
create reference curves adjusted for age, sex, ethnicity, and body size to enable
clinical application, using in vivo cross-calibration and making data back and
forward compatible. Seven UK sites collected data on GE Lunar or Hologic Scanners
between 1996 and 2012. Males and females aged 4 to 20 years were recruited (n =
3598). The split by ethnic group was white 2887; South Asian 385; black Afro
Caribbean 286; and mixed heritage 40. Scans of the total body and lumbar spine
(L1 to L4 ) were obtained. The European Spine Phantom was used to cross-calibrate
the 7 centers and 11 scanners. Reference curves were produced for L1 to L4 bone
mineral apparent density (BMAD) and total body less head (TBLH) and L1 to L4
areal bone mineral density (aBMD) for GE Lunar Prodigy and iDXA (sex- and ethnic
specific) and for Hologic (sex-specific). Regression equations for TBLH BMC were
produced using stepwise linear regression. Scans of 100 children were randomly
selected to test backward and forward compatibility of software versions, up to
version 15.0 for GE Lunar and Apex 4.1 for Hologic. For the first time, sex- and
ethnic-specific reference curves for lumbar spine BMAD, aBMD, and TBLH aBMD are
provided for both GE Lunar and Hologic scanners. These curves will facilitate
interpretation of DXA data in children using methods recommended in ISCD
guidelines. The databases have been created to allow future updates and analysis
when more definitive evidence for the best method of fracture prediction in
children is agreed. (c) 2016 American Society for Bone and Mineral Research.
PMID- 27490038
TI - Drug Side Effect Profiles as Molecular Descriptors for Predictive Modeling of
Target Bioactivity.
AB - We have explored the potential of using side effect profiles of drugs to predict
their bioactivities at the receptor level. Serotonin 5-HT6 binding and dopamine
antagonism were investigated in separate studies. A set of 5-HT6 binders and non
binders was retrieved from the PDSP Ki database, whereas dopamine antagonists
were retrieved from the MeSH Pharmaceutical Action file. The side effect data was
extracted from ChemoText, a data repository containing MeSH annotations pulled
from MEDLINE records. These side effects profiles were treated as molecular
descriptors enabling a QSAR-like approach to build models that could reliably
discriminate different classes of molecules, e.g., binders versus non-binders,
and dopamine antagonists versus non-antagonists. Selected models with the best
external prediction performances were applied to a library of ca. 1000 chemicals
with known side effects profiles in order to predict their potential 5-HT6
binding and/or dopamine antagonism. In each case the virtual screening process
was able to identify putatively active compounds that through subsequent
literature-based validation were found to be likely or known 5-HT6 binders or
dopamine antagonists. These results demonstrate that side effect profiles can be
utilized to predict a drug's unknown molecular activity, thus representing a
valuable opportunity in repositioning the drug for a new indications.
PMID- 27490039
TI - Screening Chemicals for Receptor-Mediated Toxicological and Pharmacological
Endpoints: Using Public Data to Build Screening Tools within a KNIME Workflow.
AB - Assessing compounds for their pharmacological and toxicological properties is of
great importance for industry and regulatory agencies. In this study an approach
using open source software and open access databases to build screening tools for
receptor-mediated effects is presented. The retinoic acid receptor (RAR), as a
pharmacologically and toxicologically relevant target, was chosen for this study.
RAR agonists are used in the treatment of a number of dermal conditions and
specific types of cancer, such as acute promyelocytic leukemia. However, when
administered chronically, there is strong evidence that RAR agonists cause
hepatosteatosis and liver injury. After compiling information on ligand-protein
interactions, common substructures and physico-chemical properties of ligands
were identified manually and coded into SMARTS strings. Based on these SMARTS
strings and calculated physico-chemical features, a rule-based screening workflow
was built within the KNIME platform. The workflow was evaluated on two datasets:
one with RAR agonists exclusively and another large, chemically diverse dataset
containing only a few RAR agonists. Possible modifications and applications of
screening workflows, dependent on their purpose, are presented.
PMID- 27490018
TI - METACOHORTS for the study of vascular disease and its contribution to cognitive
decline and neurodegeneration: An initiative of the Joint Programme for
Neurodegenerative Disease Research.
AB - Dementia is a global problem and major target for health care providers. Although
up to 45% of cases are primarily or partly due to cerebrovascular disease, little
is known of these mechanisms or treatments because most dementia research still
focuses on pure Alzheimer's disease. An improved understanding of the vascular
contributions to neurodegeneration and dementia, particularly by small vessel
disease, is hampered by imprecise data, including the incidence and prevalence of
symptomatic and clinically "silent" cerebrovascular disease, long-term outcomes
(cognitive, stroke, or functional), and risk factors. New large collaborative
studies with long follow-up are expensive and time consuming, yet substantial
data to advance the field are available. In an initiative funded by the Joint
Programme for Neurodegenerative Disease Research, 55 international experts
surveyed and assessed available data, starting with European cohorts, to promote
data sharing to advance understanding of how vascular disease affects brain
structure and function, optimize methods for cerebrovascular disease in
neurodegeneration research, and focus future research on gaps in knowledge. Here,
we summarize the results and recommendations from this initiative. We identified
data from over 90 studies, including over 660,000 participants, many being
additional to neurodegeneration data initiatives. The enthusiastic response means
that cohorts from North America, Australasia, and the Asia Pacific Region are
included, creating a truly global, collaborative, data sharing platform, linked
to major national dementia initiatives. Furthermore, the revised World Health
Organization International Classification of Diseases version 11 should
facilitate recognition of vascular-related brain damage by creating one category
for all cerebrovascular disease presentations and thus accelerate identification
of targets for dementia prevention.
PMID- 27490040
TI - Destructive Otologic Foreign Body: Dangers of the Expanding Bead.
PMID- 27490041
TI - Functional and structural changes of the urinary bladder following spinal cord
injury; treatment with alpha lipoic acid.
AB - BACKGROUND & AIM: Alpha lipoic acid (LA) was shown to exert neuroprotection in
trauma-induced spinal cord injury (SCI), which is frequently associated with
urinary bladder complaints in patients with SCI. Accordingly, the protective
effects of LA on biochemical and histological changes in bladder as well as
functional studies were assessed. METHODS: Wistar albino rats were divided as
control, SCI, and LA (50 mg/kg/day, ip) treated SCI groups (SCI+LA). The standard
weight-drop (100 g/cm force at T10) method was used to induce a moderately severe
SCI. One week after the injury, neurological examination was performed and the
rats were decapitated. Bladder samples were taken for histological examination,
functional (isolated tissue bath) studies, and for the measurement of biochemical
parameters (malondialdehyde, MDA; gluthathione, GSH; nerve growth factor, NGF;
caspase-3, luminol and lucigenin chemiluminescences). RESULTS: SCI caused a
significant (P < 0.001) increase in the detrusor muscle thickness. It increased
the contractility responses to carbachol and relaxation responses to papaverine
(P < 0.05-0.001). There were also significant alterations in MDA, caspase-3,
luminol, and lucigenin chemiluminescences with concomitant decreases in NGF and
GSH (P < 0.05). LA treatment reversed histological and functional (contraction
and relaxation responses) changes induced by SCI (P < 0.05-0.001), but no
significant recovery was observed in the impaired neurological functions.
CONCLUSION: These results indicate that LA have a beneficial effect in improving
the bladder tonus via its antioxidant and anti-inflammatory actions following
SCI.
PMID- 27490042
TI - Lentiviral HSV-Tk.007-mediated suicide gene therapy is not toxic for normal brain
cells.
AB - BACKGROUND: Gene therapeutic strategies with suicide genes are currently
investigated in clinical trials for brain tumors. Previously, we have shown that
lentiviral vectors delivering the suicide gene HSV-Tk to experimental brain
tumors promote a highly significant treatment effect and thus are promising
vectors for clinical translation. METHODS: In the present study, we tested
lentiviral vectors delivering the suicide gene HSV-Tk.007, a highly active mutant
of HSV-Tk, to rat brains as a preclinical toxicity study. We injected 10(6)
vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped functional lentiviral
particles harboring the suicide gene HSV-Tk.007 into the brain of healthy,
immunocompetent rats. During prodrug treatment with ganciclovir (GCV), we
measured weight and assessed the behavior of the rats in an open field test.
After 14 days of GCV treatment, we analyzed HSV-Tk.007 expression in different
brain cell populations, as well as inflammatory responses and apoptosis. RESULTS:
During prodrug treatment with GCV, behavior experiments did not reveal
differences between the treated rats and the control groups. Analysis of HSV-Tk
expression in different brain cell populations showed that transduced normal
brain cells survived GCV treatment. There were no statistically significant
differences in the number of transduced cells between treatment and control
groups. Furthermore, inflammatory responses and apoptosis of brain cells were not
observed. CONCLUSIONS: We show that HSV-Tk.007-mediated suicide gene therapy is
not toxic to normal brain cells. This observation is of high relevance for the
translation of lentivirus-mediated suicide gene therapies into the clinic for the
treatment of brain tumor patients. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27490043
TI - How does closed system vitrification of human oocytes affect the clinical
outcome? A prospective, observational, cohort, noninferiority trial in an oocyte
donation program.
AB - OBJECTIVE: To evaluate whether is possible to vitrify oocytes in an aseptic
(hermetically closed) fashion and maintain clinical results comparable with those
of fresh oocytes. DESIGN: Prospective, observational, cohort, noninferiority
trial. SETTING: Private in vitro fertilization center. PATIENT(S): One hundred
eighty-four recipients of donated vitrified oocytes. INTERVENTION(S): Closed
system vitrification. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle and
clinical pregnancy rate per cycle. RESULT(S): No statistically significant
differences were observed between two groups regarding the pregnancy rate per
cycle (63.1% vs. 60.9%) or the clinical pregnancy rate per cycle (55.4% vs.
58.7%). Biochemical pregnancy rate was statistically significantly higher in the
fresh group (7.6% vs. 2.2%). The mean number of embryos transferred was similar
(2.0 +/- 0.0 vs. 1.97 +/- 0.3). Concerning embryologic data, there were no
statistically significant differences regarding the fertilization, cleavage, top
quality day-3 embryo, or blastocyst rates, whereas the top quality blastocyst
rate on day 5 was statistically significantly higher in the fresh oocyte group
(31.7% vs. 26.1%). CONCLUSION(S): Aseptically (in a closed system) vitrified
oocytes show similar clinical efficiency compared with their sibling fresh
oocytes.
PMID- 27490045
TI - Human spermatogonial stem cells display limited proliferation in vitro under
mouse spermatogonial stem cell culture conditions.
AB - OBJECTIVE: To study the ability of human spermatogonial stem cells (hSSCs) to
proliferate in vitro under mouse spermatogonial stem cell (mSSC) culture
conditions. DESIGN: Experimental basic science study. SETTING: Reproductive
biology laboratory. PATIENT(S): Cryopreserved testicular tissue with normal
spermatogenesis obtained from three donors subjected to orchiectomy due to a
prostate cancer treatment. INTERVENTION(S): Testicular cells used to create in
vitro cell cultures corresponding to the following groups: [1] unsorted human
testicular cells, [2] differentially plated human testicular cells, and [3] cells
enriched with major histocompatibility complex class 1 (HLA-)/epithelial cell
surface antigen (EPCAM+) in coculture with inactivated testicular feeders from
the same patient. MAIN OUTCOME MEASURE(S): Analyses and characterization
including immunocytochemistry and quantitative reverse-transcription polymerase
chain reaction for somatic and germ cell markers, testosterone and inhibin B
quantification, and TUNEL assay. RESULT(S): Putative hSSCs appeared in singlets,
doublets, or small groups of up to four cells in vitro only when testicular cells
were cultured in StemPro-34 medium supplemented with glial cell line-derived
neurotrophic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast
growth factor (bFGF), and epidermal growth factor (EGF). Fluorescence-activated
cell sorting with HLA-/EPCAM+ resulted in an enrichment of 27% VASA+/UTF1+ hSSCs,
compared to 13% in unsorted controls. Coculture of sorted cells with inactivated
testicular feeders gave rise to an average density of 112 hSSCs/cm2 after 2 weeks
in vitro compared with unsorted cells (61 hSSCs/cm2) and differentially plated
cells (49 hSSCS/cm2). However, putative hSSCs rarely stained positive for the
proliferation marker Ki67, and their presence was reduced to the point of almost
disappearing after 4 weeks in vitro. CONCLUSION(S): We found that hSSCs show
limited proliferation in vitro under mSSC culture conditions. Coculture of HLA
/EPCAM+ sorted cells with testicular feeders improved the germ cell/somatic cell
ratio.
PMID- 27490044
TI - Pregnancy intentions-a complex construct and call for new measures.
AB - OBJECTIVE: To estimate the prevalence of unintended pregnancies under relaxed
assumptions regarding birth control use compared with a traditional constructed
measure. DESIGN: Cross-sectional survey. SETTING: Not applicable. PATIENT(S):
Nationally representative sample of U.S. women aged 15-44 years. INTERVENTION(S):
None. MAIN OUTCOME MEASURE(S): Prevalence of intended and unintended pregnancies
as estimated by [1] a traditional constructed measure from the National Survey of
Family Growth (NSFG), and [2] a constructed measure relaxing assumptions
regarding birth control use, reasons for nonuse, and pregnancy timing. RESULT(S):
The prevalence of unintended pregnancies was 6% higher using the traditional
constructed measure as compared with the approach with relaxed assumptions (NSFG:
44%, 95% confidence interval [CI] 41, 46; new construct 38%, 95% CI, 36, 41).
Using the NSFG approach, only 92% of women who stopped birth control to become
pregnant and 0 women who were not using contraceptives at the time of the
pregnancy and reported that they did not mind getting pregnant were classified as
having intended pregnancies, compared with 100% using the new construct.
CONCLUSION(S): Current measures of pregnancy intention may overestimate rates of
unintended pregnancy, with over 340,000 pregnancies in the United States
misclassified as unintended using the current approach, corresponding to an
estimated savings of $678 million in public health-care expenditures. Current
constructs make assumptions that may not reflect contemporary reproductive
practices, so improved measures are needed.
PMID- 27490046
TI - Dual trigger for final oocyte maturation improves the oocyte retrieval rate of
suboptimal responders to gonadotropin-releasing hormone agonist.
AB - OBJECTIVE: To identify the risk factors for suboptimal response to GnRH agonist
(GnRH-a) trigger and evaluate the effect of hCG on the outcome of patients with
suboptimal response to GnRH-a. DESIGN: A retrospective data analysis. SETTING: A
tertiary-care academic medical center. PATIENT(S): A total of 8,092 women
undergoing 8,970 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles.
INTERVENTION(S): All women underwent hMG + medroxyprogesterone acetate (MPA)/P
treatment cycles during IVF/ICSI, which were triggered using a GnRH-a alone or in
combination with hCG (1,000, 2,000, or 5,000 IU). Viable embryos were
cryopreserved for later transfer. MAIN OUTCOME MEASURE(S): The rates of oocyte
retrieval, mature oocytes, fertilization, and the number of oocytes retrieved,
mature oocytes, and embryos frozen. RESULT(S): In total, 2.71% (243/8,970) of
patients exhibited a suboptimal response to GnRH-a. The suboptimal responders (LH
<=15 mIU/mL) had a significantly lower oocyte retrieval rate (48.16% vs. 68.26%),
fewer mature oocytes (4.10 vs. 8.29), and fewer frozen embryos (2.32 vs. 3.54)
than the appropriate responders. Basal LH levels served as the single most
valuable marker for differentiating suboptimal responders with the areas under
the receiver operating curve of 0.805. Administering dual trigger (GnRH-a and hCG
1,000, 2,000, 5,000 IU) significantly increased oocyte retrieval rates (60.04%
vs. 48.16%; 68.13% vs. 48.16%; and 65.76% vs. 48.16%, respectively) in patients
with a suboptimal response. CONCLUSION(S): Basal LH level was useful predictor of
the suboptimal response to GnRH-a trigger. Administrating dual trigger including
1,000 IU hCG for final oocyte maturation could improve the oocytes retrieval rate
of GnRH-a suboptimal responder.
PMID- 27490047
TI - Morphometric Analyses by a New Slit-Lamp Endothelial Biomicroscope.
AB - PURPOSE: A method called EndoKer was recently devised for the morphometric
analysis of the cell mosaic of the corneal endothelium. Fully automatic cell
recognition is performed on images acquired by a slit-lamp biomicroscope. The aim
of this study was to evaluate the accuracy of the EndoKer results. METHODS:
Analyses were performed on a polystyrene bead layer stratified on a contact lens
and in vivo on 30 adults. Accuracy was evaluated by comparing the results of
EndoKer with the true values obtained by manual counting of the cells in the same
images. EndoKer results were also compared with those obtained with the Tomey
EM3000 microscope. RESULTS: The accuracy of the results compared with the manual
counting on the same images showed a difference of a few percent for the cell
density and for hexagonality. This high accuracy derives from (1) the resolution
of the slit-lamp images and (2) the improved cell recognition of the fully
automatic method. A good agreement was also found between EndoKer and the Tomey
EM3000 microscope results. CONCLUSIONS: Based on the investigated 30 cases, the
slit-lamp biomicroscope may be a viable alternative to dedicated endothelial
instruments, providing the additional advantages of a larger investigated area
and the possibility to take images of different portions of the cornea. The
calibration was performed during the development of the method by using
polystyrene beads. The user is not required to perform this calibration. However,
such a calibrated sample is suggested for those interested.
PMID- 27490048
TI - Intrastromal Corneal Ring Segment Implantation in 409 Paracentral Keratoconic
Eyes.
AB - PURPOSE: To assess the efficacy outcomes of implanting intrastromal corneal ring
segments (ICRS) to correct paracentral keratoconus. METHODS: Four hundred nine
eyes with paracentral keratoconus, in which the differences between the axes of
refractive cylinder and the corneal flattest meridian and the comatic aberration
map were less than 30 degrees, were evaluated before and after the implantation
of Ferrara-type ICRS. Snellen uncorrected and best-corrected distance visual
acuity, residual refractive errors analyzed with vector analysis, and the root
mean square for corneal coma-like aberration for a pupil size of 4.5 mm were
recorded before and 6 months after ICRS implantation. RESULTS: The mean
uncorrected distance visual acuity (Snellen decimal scale) rose from 0.19 +/-
0.19 before ICRS implantation to 0.42 +/- 0.30 after implantation (P < 0.0001).
The mean preoperative best-corrected distance visual acuity was 0.69 +/- 0.24 and
the postoperative value was 0.77 +/- 0.23 (P < 0.0001). The safety index was
1.13. The spherical equivalent declined steeply after ICRS implantation (P <
0.0001). Cylinder power decreased by more than 50% in 71% of the eyes. The root
mean square for corneal coma-like aberration for a 4.5-mm pupil changed from 1.32
+/- 1.01 MUm before surgery to 1.06 +/- 0.85 MUm after surgery (P <= 0.001).
CONCLUSIONS: The Ferrara-type ICRS implantation is a safe and effective procedure
for treating patients with keratoconus that meets the morphological
characteristics of the sample under study.
PMID- 27490050
TI - Toxicity of Intracameral Injection of Fourth-Generation Fluoroquinolones on the
Corneal Endothelium.
AB - PURPOSE: The aim of this study was to compare the cellular susceptibility
patterns and morphologic changes in the corneal endothelium associated with the
use of fourth-generation fluoroquinolones. METHOD: Endothelial susceptibility was
assessed through intracameral injection of besifloxacin, gatifloxacin, and
moxifloxacin. Human umbilical vein endothelial cells (HUVECs) were used as the
standard cellular lineage to assess the quantitative toxicity of each antibiotic
solution. Qualitative changes in the morphologic character of the corneal
structure and the endothelial layer were generated using a combination of ex vivo
and in vivo assays. Experimental assays were conducted in triplicate, and the
results were statistically analyzed. RESULTS: At 1 hour of exposure, all HUVECs
exposed to antibiotics showed viability above 85%, after 3 hours of exposure to
besifloxacin, gatifloxacin, and moxifloxacin, the percentages of viable cells
were 68.3 +/- 4.0 (P < 0.001), 90.7 +/- 4.2 (P < 0.05), and 93.3 +/- 1.5 (P >
0.05), respectively. All fluoroquinolones tested showed toxicity to HUVECs,
resulting in significant (P < 0.001) loss of cellular viability after 24 hours of
drug exposure. Giant endothelial cells were observed in animals treated with the
3 fluoroquinolones in contrast to the absence of these abnormal cells in the
untreated group. Early cellular detachment was seen in the endothelial layer
after exposure to gatifloxacin and moxifloxacin. CONCLUSIONS: We concluded that
injection of fourth-generation fluoroquinolones in the aqueous humor did not
adversely affect the corneal endothelium. However, these results suggested that
prophylactic intracameral injection of besifloxacin, gatifloxacin, or
moxifloxacin, if needed, should be administered as a last therapeutic resource in
clinical practice, with careful and constant monitoring of corneal endothelium.
PMID- 27490049
TI - MicroRNA-29b Overexpression Decreases Extracellular Matrix mRNA and Protein
Production in Human Corneal Endothelial Cells.
AB - PURPOSE: MicroRNAs are small noncoding RNAs that regulate gene expression at the
posttranscriptional level. We reported that levels of microRNA (miR)-29 family
are decreased in corneas of patients with Fuchs endothelial corneal dystrophy
(FECD). The miR-29 family regulates the production of extracellular matrix (ECM)
proteins. Accumulation of ECM proteins in Descemet membrane is an important
pathologic change in FECD. In this study, we transfected miR-29b into human
corneal endothelial cells and tissues and evaluated ECM protein expression
levels. METHODS: An immortalized Fuchs human corneal endothelial cell line
(iFECD) was established by infection of corneal endothelial cells from patients
with FECD with hTERT lentivirus. MiR-29b was transfected into iFECD, and the
expression levels of ECMs collagen type 1 alpha 1 (COL1A1), collagen type 4 alpha
1 (COL4A1), and laminin gamma 1 (LAMC1) were evaluated with quantitative reverse
transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Expression
level of LAMC1 protein in miR-29b-transfected donor corneal endothelium was also
evaluated by Western blot. RESULTS: Compared with control, miR-29b expression
level after transfection of iFECD was increased to 335.6% (+/-91.0%), and ECM
expression levels were significantly decreased. Compared with control, qRT-PCR
demonstrated reduction of ECM to the following levels: COL1A1: 1.9% (+/-0.4%);
COL4A1: 7.1% (+/-1.7%); and LAMC1: 21.5% (+/-2.7%). Western blot showed reduced
protein expression: COL1A1: 4.8% (+/-3.2%); COL4A1: 42.5% (+/-25.0%); and LAMC1:
44.8% (+/-3.1%). In miR-29b-transfected corneal tissue, LAMC1 protein expression
level was decreased to 14.4% (+/-20.5%). CONCLUSIONS: Overexpression of miR-29b
decreased ECM protein production in human corneal endothelial cells. Thus, miR-29
replacement therapy might be a new treatment strategy for FECD aimed at reducing
pathologic production of ECM proteins in Descemet membrane.
PMID- 27490051
TI - Association Between Corneal Endothelial Cell Density and Topical Glaucoma
Medication Use in an Eye Bank Donor Population.
AB - PURPOSE: To evaluate the association between corneal endothelial cell density
(ECD) and donor topical glaucoma medication use in an eye bank database. METHODS:
Raw eye bank data included 19,159 donors over the period July 2007 to May 2015.
Free-text, donor medication lists were retrospectively searched for glaucoma
medication. Exclusion criteria were age less than 40 years, history of eye
surgery, endothelial trauma, guttae, and cell densities <1000 or >3300/mm.
Analysis of covariance was used to test differences in cell density between
groups while adjusting for age. Linear regression was used to test the
correlation of independent interval variables while adjusting for age. RESULTS:
Twelve thousand one hundred fifty-seven donors were included in the final
analysis; 134 were on topical glaucoma medication. The mean ECD for donors not on
glaucoma medication and pooled donors on glaucoma medication was 2561 +/- 348 and
2516 +/- 320 cells/mm, respectively (P = 0.42). Subgroup analysis by medication
class resulted in nonstatistically significant differences between ECDs of
nonmedicated donors and donors on alpha agonists (P = 0.76), beta blockers (P =
0.90), carbonic anhydrase inhibitors (P = 0.13), cholinergics (P = 0.37), and
prostaglandin analogs (P = 0.62). The number of glaucoma medication classes used
by donors was not a statistically significant predictor of endothelial density (P
= 0.298). CONCLUSIONS: Donors on topical glaucoma medication do not have ECDs
statistically significantly lower than donors not on medication.
PMID- 27490052
TI - Interface Fluid Syndrome After Laser In Situ Keratomileusis (LASIK) Because of
Fuchs Endothelial Dystrophy Reversed by Descemet Membrane Endothelial
Keratoplasty (DMEK).
AB - PURPOSE: To describe a case that developed "interface fluid syndrome" after
previous laser in situ keratomileusis (LASIK) because of Fuchs endothelial
dystrophy (FED), which was reversed by Descemet membrane endothelial keratoplasty
(DMEK). METHODS: A 58-year-old male patient presented with bilateral visual
impairment owing to FED and visually significant cataract. Cataract surgery was
carried out in both eyes followed by DMEK in his left eye. RESULTS: After
cataract surgery, visual acuity did not improve sufficiently because corneal
thickness increased and a fine cleft with interface fluid developed between the
LASIK-flap and the residual stromal bed. After uneventful DMEK in his left eye,
the fluid resolved within a week and visual acuity improved rapidly. CONCLUSIONS:
This case demonstrates that "interface fluid syndrome" after LASIK caused by
concomitant endothelial dysfunction may be reversed by DMEK allowing fast visual
recovery.
PMID- 27490053
TI - Bilateral Urrets-Zavalia Syndrome After Descemet Stripping Automated Endothelial
Keratoplasty.
AB - PURPOSE: To report a case of bilateral Urrets-Zavalia syndrome (UZS) after
Descemet stripping automated endothelial keratoplasty (DSAEK). METHODS: Case
report. RESULTS: A 61-year-old patient with Fuchs endothelial dystrophy initially
developed UZS in the left eye after DSAEK. Thirteen months later, she underwent
combined cataract surgery and DSAEK in the right eye, and postoperatively she was
noted to have elevated intraocular pressure and a fixed and dilated pupil on the
first postoperative day. Both pupils showed partial improvement in reactivity
over the course of weeks to months. This is the first case of bilateral UZS after
DSAEK surgery and in a patient with Fuchs dystrophy. CONCLUSIONS: UZS may occur
bilaterally after DSAEK. Because elevated intraocular pressure has been shown to
be a risk factor for this condition, this should be monitored closely during the
postoperative period.
PMID- 27490054
TI - Increased Straylight in Patients With Keratoconjunctivitis Sicca.
PMID- 27490055
TI - Reply.
PMID- 27490057
TI - Open Access and Online Journals in Orthopaedics: What Does the Future Hold?
PMID- 27490056
TI - Three-dimensional synaptic analyses of mitral cell and external tufted cell
dendrites in rat olfactory bulb glomeruli.
AB - Recent studies have suggested that the two excitatory cell classes of the
mammalian olfactory bulb, the mitral cells (MCs) and tufted cells (TCs), differ
markedly in physiological responses. For example, TCs are more sensitive and
broadly tuned to odors than MCs and also are much more sensitive to stimulation
of olfactory sensory neurons (OSNs) in bulb slices. To examine the morphological
bases for these differences, we performed quantitative ultrastructural analyses
of glomeruli in rat olfactory bulb under conditions in which specific cells were
labeled with biocytin and 3,3'-diaminobenzidine. Comparisons were made between
MCs and external TCs (eTCs), which are a TC subtype in the glomerular layer with
large, direct OSN signals and capable of mediating feedforward excitation of MCs.
Three-dimensional analysis of labeled apical dendrites under an electron
microscope revealed that MCs and eTCs in fact have similar densities of several
chemical synapse types, including OSN inputs. OSN synapses also were distributed
similarly, favoring a distal localization on both cells. Analysis of unlabeled
putative MC dendrites further revealed gap junctions distributed uniformly along
the apical dendrite and, on average, proximally with respect to OSN synapses. Our
results suggest that the greater sensitivity of eTCs vs. MCs is due not to OSN
synapse number or absolute location but rather to a conductance in the MC
dendrite that is well positioned to attenuate excitatory signals passing to the
cell soma. Functionally, such a mechanism could allow rapid and dynamic control
of OSN-driven action potential firing in MCs through changes in gap junction
properties. J. Comp. Neurol. 525:592-609, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490058
TI - Acute Distal Radioulnar Joint Instability in Adults: A Critical Analysis Review.
PMID- 27490059
TI - Defining Value in Hip and Knee Arthroplasty in the United States.
PMID- 27490060
TI - Complex Regional Pain Syndrome.
PMID- 27490061
TI - Understanding Multiple Sclerosis: Essentials for the Orthopaedic Surgeon.
PMID- 27490062
TI - Evaluation and Treatment of Scaphoid Nonunions: A Critical Analysis Review.
PMID- 27490063
TI - Arthroscopic Single-Row Versus Double-Row Repair for Full-Thickness
Posterosuperior Rotator Cuff Tears: A Critical Analysis Review.
PMID- 27490064
TI - Heat equation inversion framework for average SAR calculation from magnetic
resonance thermal imaging.
AB - Deposition of radiofrequency (RF) energy can be quantified via electric field or
temperature change measurements. Magnetic resonance imaging has been used as a
tool to measure three dimensional small temperature changes associated with RF
radiation exposure. When duration of RF exposure is long, conversion from
temperature change to specific absorption rate (SAR) is nontrivial due to
prominent heat-diffusion and conduction effects. In this work, we demonstrated a
method for calculation of SAR via an inversion of the heat equation including
heat-diffusion and conduction effects. This method utilizes high-resolution three
dimensional magnetic resonance temperature images and measured thermal properties
of the phantom to achieve accurate calculation of SAR. Accuracy of the proposed
method was analyzed with respect to operating frequency of a dipole antenna and
parameters used in heat equation inversion. Bioelectromagnetics. 37:493-503,
2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490065
TI - Unusual Photophobia in a Child.
PMID- 27490067
TI - Care of Patients at the End of Life: Foreword.
PMID- 27490066
TI - Ventilation, indoor air quality, and health in homes undergoing weatherization.
AB - Ventilation standards, health, and indoor air quality have not been adequately
examined for residential weatherization. This randomized trial showed how ASHRAE
62-1989 (n=39 houses) and ASHRAE 62.2-2010 (n=42 houses) influenced ventilation
rates, moisture balance, indoor air quality, and self-reported physical and
mental health outcomes. Average total airflow was nearly twice as high for ASHRAE
62.2-2010 (79 vs. 39 cfm). Volatile organic compounds, formaldehyde and carbon
dioxide were all significantly reduced for the newer standard and first-floor
radon was marginally lower, but for the older standard, only formaldehyde
significantly decreased. Humidity in the ASHRAE 62.2-2010 group was only about
half that of the ASHRAE 62-1989 group using the moisture balance metric. Radon
was higher in the basement but lower on the first floor for ASHRAE 62.2-2010.
Children in each group had fewer headaches, eczema, and skin allergies after
weatherization and adults had improvements in psychological distress. Indoor air
quality and health improve when weatherization is accompanied by an ASHRAE
residential ventilation standard, and the 2010 ASHRAE standard has greater
improvements in certain outcomes compared to the 1989 standard. Weatherization,
home repair, and energy conservation projects should use the newer ASHRAE
standard to improve indoor air quality and health.
PMID- 27490068
TI - Care of Patients at the End of Life: Pharmacotherapeutic Management of Pain.
AB - End-of-life care often involves management of pain. A patient's pain should be
assessed using the Visual Analogue Scale, which uses a 0 to 10 score, with 0
indicating no pain and 10 the worst pain imaginable. Mild pain typically is
managed with nonopioids (eg, acetaminophen, nonsteroidal anti-inflammatory
drugs). More severe pain is managed with opioids. Opioid therapy should start
with an immediate-release opioid to determine the dose needed to achieve pain
control. This can be used to create a regimen with an extended-release
formulation for daily pain management plus an immediate-release formulation for
breakthrough pain. The breakthrough dose should be 10% to 15% of the total daily
dosage administered every 2 to 3 hours. If there is a need to change opioids or
convert from oral to parenteral opioids, a conversion table should be used to
estimate the new dosage. Patients taking opioids often experience constipation,
so also prescribing a laxative (eg, senna, sorbitol) is advised. Other adverse
effects of opioids mainly occur when starting or increasing the dosage. These
effects include nausea, sedation, neurotoxicity, and itching, and typically
resolve in several days. Adjuvant drugs (eg, antidepressants, anticonvulsants)
often are added to the opioid regimen, particularly for management of neuropathic
pain.
PMID- 27490069
TI - Care of Patients at the End of Life: Management of Nonpain Symptoms.
AB - Management of nonpain symptoms can improve quality of life for patients at the
end of life and their family members. Constipation is the most common nonpain
symptom. It can be related to opioid therapy and/or medical conditions. After
abdominal examination to detect masses or evidence of bowel obstruction and
rectal examination to exclude fecal impaction, constipation should be managed
with a stimulant laxative (eg, senna) or an osmotic laxative (eg, sorbitol).
Dyspnea also is common, and often improves with use of a fan to blow air into the
face, as well with breathing and relaxation exercises. However, many patients
require titrated doses of opioids to address respiratory depression, and
anxiolytics such as haloperidol may be needed to manage dyspnea-related anxiety.
Oxygen typically is not effective in dyspnea management in nonhypoxemic patients
at the end of life. Cough is managed with antitussives. Nausea and vomiting occur
in 70% of patients in palliative care units. If no reversible etiology can be
identified, dopamine antagonists and motility-enhancing drugs can be used. There
are no clearly effective treatments to manage noisy respiratory secretions, but
position change, decrease in fluid intake, and drugs such as scopolamine or
glycopyrrolate may be effective.
PMID- 27490070
TI - Care of Patients at the End of Life: Advance Care Planning.
AB - Advance directives are legal documents that give instructions about how to
provide care when patients develop life-threatening illnesses and can no longer
communicate their wishes. Two types of documents are widely used-a living will
and a durable power of attorney for health care. Most states also authorize
physician orders for life-sustaining treatment. Physicians should encourage
patients, particularly those with severe chronic or terminal conditions, to
prepare advance directives. Medicare now reimburses billing codes for advance
care consultations. Directions regarding cardiopulmonary resuscitation and
artificial ventilation often are included in advance care plans, and use of
artificial nutrition and hydration (ANH) also should be addressed, particularly
for patients with advanced dementia. Evidence shows that in such patients, ANH
does not prolong survival, increase comfort, or improve quality of life. Given
the lack of benefit, physicians should recommend against use of ANH for patients
with dementia. Finally, physicians should encourage use of hospice services by
patients whose life expectancy is 6 months or less. Although Medicare and most
other health care insurers cover hospice care, and despite evidence that patient
and family satisfaction increase when hospice services are used, many patients do
not use these services.
PMID- 27490071
TI - Care of Patients at the End of Life: Surrogate Decision Making for Incapacitated
Patients.
AB - Competence is determined by a court of law, whereas physicians determine medical
decision-making capacity (DMC). When patients lack DMC, a surrogate should be
identified to make decisions. Ideally, patients will have created a durable power
of attorney for health care. If a patient did not do this, state statutes specify
which individuals can serve as surrogates; a current spouse typically is the
first choice. Ideally, surrogates should use substituted judgment in making
decisions. If this is not possible because the patient never shared end-of-life
wishes with the surrogate, the surrogate can make decisions that, in the
surrogate's opinion, are in the patient's best interests or that a reasonable
individual would make. When no surrogate can be identified and a patient has no
written advance directive, hospital ethics committees can assist with decisions,
or, for some patients, a court will need to appoint a guardian. When there is a
surrogate, difficulties can arise when family members disagree with the
surrogate's decisions or when surrogates request treatments that, in the
physician's opinion, would be futile or nonbeneficial. Hospital ethics committees
may be able to assist in these situations, but appropriately conducted family
meetings often resolve such difficulties.
PMID- 27490072
TI - Orthopaedic Quality Reporting: A Comprehensive Review of the Current Landscape
and a Roadmap for Progress.
PMID- 27490073
TI - The Evaluation and Treatment of Pediatric Tarsal Coalitions: A Critical Analysis
Review.
PMID- 27490074
TI - Emerging Technologies for the Diagnosis of Periprosthetic Infection.
PMID- 27490075
TI - The Treatment of Periprosthetic Femoral Fractures After Total Hip Arthroplasty: A
Critical Analysis Review.
PMID- 27490076
TI - Spinopelvic Balance.
PMID- 27490077
TI - The Mucosal Innate Immune Response in Primary Human Papillomavirus Infection: A
Pilot Study.
AB - OBJECTIVES: The purpose of the study was to evaluate the mucosal immune response
in women affected by primary human papillomavirus (HPV) infection, in comparison
with HPV-negative women with no previous history of HPV. METHODS: A case-control
study comparing the activity of myeloperoxidase (MPO) and lactoferrin (LF)
between 19 HPV-positive and 19 HPV-negative women matched for age. Plasmatic and
cervicovaginal levels of polymorphonuclear neutrophils (PMN) exhibiting MPO and
LF receptors were measured using cytofluorimetric analysis and expressed as mean
of percentages. RESULTS: Cervicovaginal levels of MPO-/LF- PMN were lower among
HPV-negative women, with a mean rate of 18.81% (SD, 21.38), as opposed to a mean
rate of 35.56% (SD, 21.02) (P = 0.020) in HPV-positive women. A similar
significant difference was not proven in plasma. The mean rates of plasmatic
levels of MPO-/LF- PMN were 36.21% (SD, 16.87) and 36.93% (SD, 10.54) (P = 0.875)
in cases and controls, respectively. All patients were evaluated 1 year later,
and only 6 cases became negative. CONCLUSIONS: The presence of MPO-/LF- PMN has
been considered as a marker of lower rate of apoptosis of HPV-infected cells.
This could explain why HPV-positive women are less capable to deal with a primary
infection.
PMID- 27490078
TI - Human Papillomavirus Types Involved in External Genital Warts in a Group of
Argentinian Women in Buenos Aires.
AB - OBJECTIVES: The aim of the study was to understand which human papillomavirus
(HPV) types are involved in external genital warts (GWs) in a group of
Argentinian women in Buenos Aires. METHODS: One hundred sixty consecutive women
15 to 45 years old with GWs were enrolled. All patients underwent confirmatory
biopsy. In 150 of 160 patients, the diagnosis of GWs was confirmed by histology,
DNA-HPV was investigated using polymerase chain reaction, and sequence analysis
with generic primers MY09/11 was performed. RESULTS: HPV 6 and/or 11 was detected
in 93.3% patients (140/150). HPV 6 was by far the most common type (80%),
followed by HPV 11 (12.7%). Coinfection with these 2 types occurred in 0.7%. HPV
16 was found in 2% and HPV 73 in 0.7%. CONCLUSION: HPV 6 and/or 11 are present in
93.3% (95% confidence interval, 0.9-1.0) of external genital warts in a group of
Argentinian women in Buenos Aires and, therefore, could be prevented with HPV
vaccine (NCT 015998779).
PMID- 27490080
TI - Spotlights on our sister journals: ChemPhysChem 15/2016.
PMID- 27490079
TI - Human Papillomavirus-Induced Squamous Intraepithelial Lesions in Vulvar Lichen
Planus.
AB - OBJECTIVES: Approximately 50% of vulvar cancers arise after transforming
infections with human papilloma virus (HPV) via the precursor squamous
intraepithelial lesion (SIL). Lichen planus (LP)-associated vulvar cancers are
typically HPV negative and arise via the precursor differentiated vulvar
intraepithelial neoplasia (d-VIN). METHODS: An index case of vulvar high-grade
squamous intraepithelial lesion (H-SIL) in an LP patient prompted this 12-year
retrospective analysis about frequency of HPV-induced SIL in 785 biopsies of 584
patients with vulvar LP. All SIL were analyzed for p53 and p16 overexpression and
for presence of DNA of 32 HPV subtypes. RESULTS: Nine (1.6%) of 584 women with
papular (3) and mucosal "erosive" LP (6) presented with H-SIL (7) and low-grade
SIL (2). All SILs harbored HPV16-DNA and showed p16-overexpression. Concomitant
immune suppression included T-suppressor lymphocyte deficit (1), systemic (1),
and topical (2) cortisone therapy. H-SILs regressed spontaneously (1) or after
imiquimod therapy (3). Three women with erosive LP discontinued imiquimod because
of side effects and had laser destruction (1), skinning vulvectomy (1), and
surgery (1) for definitive treatment. Two women have recurrent vulvar SILs, and 1
woman progressed to invasive SCC. In the same patient population, 16 of 584 women
had a d-VIN, and 9 of 16 with progression to SCC. CONCLUSIONS: H-SILs in vulvar
LP are rare and may occur in the setting of risk factors. If clinical suspicion
arises, biopsy and histological examination assist in correct etiologic
classification of a precancerous lesion and subsequent therapy decisions. The
minimal risk for H-SIL development in vulvar LP patients should not preclude
therapy of LP.
PMID- 27490081
TI - Environmental Isolation of Circulating Vaccine-Derived Poliovirus After
Interruption of Wild Poliovirus Transmission - Nigeria, 2016.
AB - In September 2015, more than 1 year after reporting its last wild poliovirus
(WPV) case in July 2014 (1), Nigeria was removed from the list of countries with
endemic poliovirus transmission,* leaving Afghanistan and Pakistan as the only
remaining countries with endemic WPV. However, on April 29, 2016, a laboratory
confirmed, circulating vaccine-derived poliovirus type 2 (cVDPV2) isolate was
reported from an environmental sample collected in March from a sewage effluent
site in Maiduguri Municipal Council, Borno State, a security-compromised area in
northeastern Nigeria. VDPVs are genetic variants of the vaccine viruses with the
potential to cause paralysis and can circulate in areas with low population
immunity. The Nigeria National Polio Emergency Operations Center initiated
emergency response activities, including administration of at least 2 doses of
oral poliovirus vaccine (OPV) to all children aged <5 years through mass
campaigns; retroactive searches for missed cases of acute flaccid paralysis
(AFP), and enhanced environmental surveillance. Approximately 1 million children
were vaccinated in the first OPV round. Thirteen previously unreported AFP cases
were identified. Enhanced environmental surveillance has not resulted in
detection of additional VDPV isolates. The detection of persistent circulation of
VDPV2 in Borno State highlights the low population immunity, surveillance
limitations, and risk for international spread of cVDPVs associated with
insurgency-related insecurity. Increasing vaccination coverage with additional
targeted supplemental immunization activities and reestablishment of effective
routine immunization activities in newly secured and difficult-to-reach areas in
Borno is urgently needed.
PMID- 27490083
TI - My Time as Editor-in-Chief: What a Long Strange Trip It's Been.
PMID- 27490084
TI - Simulation in Healthcare: Growin' up.
PMID- 27490082
TI - Interactions between 4-aminoquinoline and heme: Promising mechanism against
Trypanosoma cruzi.
AB - Chagas disease is a neglected tropical disease caused by the flagellated
protozoan Trypanosoma cruzi. The current drugs used to treat this disease have
limited efficacy and produce severe side effects. Quinolines, nitrogen
heterocycle compounds that form complexes with heme, have a broad spectrum of
antiprotozoal activity and are a promising class of new compounds for Chagas
disease chemotherapy. In this study, we evaluated the activity of a series of 4
arylaminoquinoline-3-carbonitrile derivatives against all forms of Trypanosoma
cruzi in vitro. Compound 1g showed promising activity against epimastigote forms
when combined with hemin (IC50<1 MUM), with better performance than benznidazole,
the reference drug. This compound also inhibited the viability of trypomastigotes
and intracellular amastigotes. The potency of 1g in combination with heme was
enhanced against epimastigotes and trypomastigotes, suggesting a similar
mechanism of action that occurs in Plasmodium spp. The addition of hemin to the
culture medium increased trypanocidal activity of analog 1g without changing the
cytotoxicity of the host cell, reaching an IC50 of 11.7 MUM for trypomastigotes.
The mechanism of action was demonstrated by the interaction of compound 1g with
hemin in solution and prevention of heme peroxidation. Compound 1g and heme
treatment induced alterations of the mitochondrion-kinetoplast complex in
epimastigotes and trypomastigotes and also, accumulation of electron-dense
deposits in amastigotes as visualized by transmission electron microscopy. The
trypanocidal activity of 4-aminoquinolines and the elucidation of the mechanism
involving interaction with heme is a neglected field of research, given the
parasite's lack of heme biosynthetic pathway and the importance of this cofactor
for parasite survival and growth. The results of this study can improve and guide
rational drug development and combination treatment strategies.
PMID- 27490085
TI - Reporting Guidelines for Health Care Simulation Research: Where Is the learning?
AB - STATEMENT: This is a commentary on the reporting guidelines article and offers
some food for thought on the need to include learning and instructional feature
variables in the reporting process.
PMID- 27490086
TI - Efficacy of a multifactorial strategy for bowel preparation in diabetic patients
undergoing colonoscopy: a randomized trial.
AB - : Background and study aims: Previous studies have reported that diabetes
mellitus is an independent risk factor for inadequate bowel preparation. Current
guidelines do not recommend a specific preparation for this patient population.
The aims of this study were to assess the efficacy, safety, and tolerability of
an adapted preparation protocol for colon cleansing in patients with type 2
diabetes mellitus. Patients and methods: This randomized, single-blind, parallel
group, superiority trial compared a conventional bowel preparation protocol (CBP)
with a diabetes-specific preparation protocol (DSP). The CBP included a low-fiber
diet for 3 days followed by a clear liquid diet for 24 hours before colonoscopy.
The DSP included a multifactorial strategy combining an educational intervention,
a low-fiber diet, and adjustment of blood glucose-lowering agents. All patients
received 4 L of a polyethylene glycol solution in a split-dose regimen. The
endoscopists were blinded to the preparation protocol. The primary outcome
measure was inadequate bowel preparation according to the Boston Bowel
Preparation Scale. Secondary outcome measures included hypoglycemic events,
tolerability, and acceptability. Results: A total of 150 patients were included
in the study (74 CBP and 76 DSP). Both groups were comparable in terms of
baseline characteristics. Inadequate bowel cleansing was more frequent following
CBP than DSP (20 % vs. 7 %, P = 0.014; risk ratio 3.1, 95 % confidence interval
1.2 - 8). Only CBP and performance status were independently associated with
inadequate bowel preparation. Both preparations were equally tolerated and
accepted by patients, and side-effects were similar between the groups.
Conclusions: A multifactorial strategy for bowel preparation in patients with
diabetes undergoing colonoscopy showed a threefold reduction in the rate of
inadequate bowel preparation, with no differences in safety and tolerability
compared with conventional preparation. TRIAL REGISTRATION: ClinicalTrials.gov
(NCT02300779).
PMID- 27490087
TI - Update: Ongoing Zika Virus Transmission - Puerto Rico, November 1, 2015-July 7,
2016.
AB - Zika virus is a flavivirus transmitted primarily by Aedes aegypti and Aedes
albopictus mosquitoes, and infection can be asymptomatic or result in an acute
febrile illness with rash (1). Zika virus infection during pregnancy is a cause
of microcephaly and other severe birth defects (2). Infection has also been
associated with Guillain-Barre syndrome (GBS) (3) and severe thrombocytopenia
(4,5). In December 2015, the Puerto Rico Department of Health (PRDH) reported the
first locally acquired case of Zika virus infection. This report provides an
update to the epidemiology of and public health response to ongoing Zika virus
transmission in Puerto Rico (6,7). A confirmed case of Zika virus infection is
defined as a positive result for Zika virus testing by reverse transcription
polymerase chain reaction (RT-PCR) for Zika virus in a blood or urine specimen. A
presumptive case is defined as a positive result by Zika virus immunoglobulin M
(IgM) enzyme-linked immunosorbent assay (MAC-ELISA)* and a negative result by
dengue virus IgM ELISA, or a positive test result by Zika IgM MAC-ELISA in a
pregnant woman. An unspecified flavivirus case is defined as positive or
equivocal results for both Zika and dengue virus by IgM ELISA. During November 1,
2015-July 7, 2016, a total of 23,487 persons were evaluated by PRDH and CDC
Dengue Branch for Zika virus infection, including asymptomatic pregnant women and
persons with signs or symptoms consistent with Zika virus disease or suspected
GBS; 5,582 (24%) confirmed and presumptive Zika virus cases were identified.
Persons with Zika virus infection were residents of 77 (99%) of Puerto Rico's 78
municipalities. During 2016, the percentage of positive Zika virus infection
cases among symptomatic males and nonpregnant females who were tested increased
from 14% in February to 64% in June. Among 9,343 pregnant women tested, 672 had
confirmed or presumptive Zika virus infection, including 441 (66%) symptomatic
women and 231 (34%) asymptomatic women. One patient died after developing severe
thrombocytopenia (4). Evidence of Zika virus infection or recent unspecified
flavivirus infection was detected in 21 patients with confirmed GBS. The
widespread outbreak and accelerating increase in the number of cases in Puerto
Rico warrants intensified vector control and personal protective behaviors to
prevent new infections, particularly among pregnant women.
PMID- 27490088
TI - Self-Assembled Redox Dual-Responsive Prodrug-Nanosystem Formed by Single
Thioether-Bridged Paclitaxel-Fatty Acid Conjugate for Cancer Chemotherapy.
AB - Chemotherapeutic efficacy can be greatly improved by developing nanoparticulate
drug delivery systems (nano-DDS) with high drug loading capacity and smart
stimulus-triggered drug release in tumor cells. Herein, we report a novel redox
dual-responsive prodrug-nanosystem self-assembled by hydrophobic small-molecule
conjugates of paclitaxel (PTX) and oleic acid (OA). Thioether linked conjugates
(PTX-S-OA) and dithioether inserted conjugates (PTX-2S-OA) are designed to
respond to the redox-heterogeneity in tumor. Dithioether has been reported to
show redox dual-responsiveness, but we find that PTX-S-OA exhibits superior redox
sensitivity over PTX-2S-OA, achieving more rapid and selective release of free
PTX from the prodrug nanoassemblies triggered by redox stimuli. PEGylated PTX-S
OA nanoassemblies, with impressively high drug loading (57.4%), exhibit potent
antitumor activity in a human epidermoid carcinoma xenograft. This novel prodrug
nanosystem addresses concerns related to the low drug loading and inefficient
drug release from hydrophobic prodrugs of PTX, and provides possibilities for the
development of redox dual-sensitive conjugates or polymers for efficient
anticancer drug delivery.
PMID- 27490089
TI - Targeted Mutagenesis and Combinatorial Library Screening Enables Control of
Protein Orientation on Surfaces and Increased Activity of Adsorbed Proteins.
AB - While nonspecific adsorption is widely used for immobilizing proteins on solid
surfaces, the random nature of protein adsorption may reduce the activity of
immobilized proteins due to occlusion of the active site. We hypothesized that
the orientation a protein assumes on a given surface can be controlled by
systematically introducing mutations into a region distant from its active site,
thereby retaining activity of the immobilized protein. To test this hypothesis,
we generated a combinatorial protein library by randomizing six targeted residues
in a binding protein derived from highly stable, nonimmunoglobulin Sso7d
scaffold; mutations were targeted in a region that is distant from the binding
site. This library was screened to isolate binders that retain binding to its
cognate target (chicken immunoglobulin Y, cIgY) as well as exhibit adsorption on
unmodified silica at pH 7.4 and high ionic strength conditions. A single mutant,
Sso7d-2B5, was selected for further characterization. Sso7d-2B5 retained binding
to cIgY with an apparent dissociation constant similar to that of the parent
protein; both mutant and parent proteins saturated the surface of silica with
similar densities. Strikingly, however, silica beads coated with Sso7d-2B5 could
achieve up to 7-fold higher capture of cIgY than beads coated with the parent
protein. These results strongly suggest that mutations introduced in Sso7d-2B5
alter its orientation relative to the parent protein, when adsorbed on silica
surfaces. Our approach also provides a generalizable strategy for introducing
mutations in proteins so as to improve their activity upon immobilization, and
has direct relevance to development of protein-based biosensors and biocatalysts.
PMID- 27490090
TI - Probing the Interior Crystal Quality in the Development of More Efficient and
Smaller Upconversion Nanoparticles.
AB - Optical biomedical imaging using luminescent nanoparticles as contrast agents
prefers small size, as they can be used at high dosages and efficiently cleared
from body. Reducing nanoparticle size is critical for the stability and
specificity for the fluorescence nanoparticles probes for in vitro diagnostics
and subcellular imaging. The development of smaller and brighter upconversion
nanoparticles (UCNPs) is accordingly a goal for complex imaging in
bioenvironments. At present, however, small UCNPs are reported to exhibit less
emission intensity due to increased surface deactivation and decreased number of
dopants. Here we show that smaller and more efficient UCNPs can be made by
improving the interior crystal quality via controlling heating rate during
synthesis. We further developed a unique quantitative method for optical
characterizations on the single UCNPs with varied sizes and the corresponding
shell passivated UCNPs, confirming that the internal crystal quality dominates
the relative emission efficiency of the UCNPs.
PMID- 27490091
TI - Cerasoidine, a Bis-aporphine Alkaloid Isolated from Polyalthia cerasoides during
Screening for Wnt Signal Inhibitors.
AB - A new bis-aporphine alkaloid, cerasoidine (1), was isolated from the root extract
of Polyalthia cerasoides together with the known bis-aporphine bidebiline E (2)
during screening for compounds with Wnt signal inhibitory activities. The
structure of cerasoidine (1) was established by X-ray analysis and shown by
chiral HPLC analyses and electronic circular dichroism to be a 57:43 mixture of
R(-)- and S(+)-atropisomers. Bidebiline E (2) exhibited inhibition of
transcriptional activity of TCF/beta-catenin with an IC50 value of 20.2 MUM and
was also found to inhibit Wnt signaling by decreasing nuclear beta-catenin.
PMID- 27490092
TI - Catalytic Asymmetric Synthesis of Ketene Heterodimer beta-Lactones: Scope and
Limitations.
AB - In this article we describe extensive studies of the catalytic asymmetric
heterodimerization of ketenes to give ketene heterodimer beta-lactones. The
optimal catalytic system was determined to be a cinchona alkaloid derivative (TMS
quinine or Me-quinidine). The desired ketene heterodimer beta-lactones were
obtained in good to excellent yields (up to 90%), with excellent levels of
enantioselectivity (>=90% ee for 33 Z and E isomer examples), good to excellent
(Z)-olefin isomer selectivity (>=90:10 for 20 examples), and excellent
regioselectivity (only one regioisomer formed). Full details of catalyst
development studies, catalyst loading investigations, substrate scope
exploration, protocol innovations (including double in situ ketene generation for
7 examples), and an application to a cinnabaramide A intermediate are described.
The addition of lithium perchlorate (1-2 equiv) as an additive to the alkaloid
catalyst system was found to favor formation of the E isomer of the ketene
heterodimer. Ten examples were formed with moderate to excellent (E)-olefin
isomer selectivity (74:25 to 97:3) and with excellent enantioselectivity (84-98%
ee).
PMID- 27490093
TI - Context-specific functional module based drug efficacy prediction.
AB - BACKGROUND: It is necessary to evaluate the efficacy of individual drugs on
patients to realize personalized medicine. Testing drugs on patients in clinical
trial is the only way to evaluate the efficacy of drugs. The approach is labour
intensive and requires overwhelming costs and a number of experiments. Therefore,
preclinical model system has been intensively investigated for predicting the
efficacy of drugs. Current computational drug sensitivity prediction approaches
use general biological network modules as their prediction features. Therefore,
they miss indirect effectors or the effects from tissue-specific interactions.
RESULTS: We developed cell line specific functional modules. Enriched scores of
functional modules are utilized as cell line specific features to predict the
efficacy of drugs. Cell line specific functional modules are clusters of genes,
which have similar biological functions in cell line specific networks. We used
linear regression for drug efficacy prediction. We assessed the prediction
performance in leave-one-out cross-validation (LOOCV). Our method was compared
with elastic net model, which is a popular model for drug efficacy prediction. In
addition, we analysed drug sensitivity-associated functions of five drugs -
lapatinib, erlotinib, raloxifene, tamoxifen and gefitinib- by our model.
CONCLUSIONS: Our model can provide cell line specific drug efficacy prediction
and also provide functions which are associated with drug sensitivity. Therefore,
we could utilize drug sensitivity associated functions for drug repositioning or
for suggesting secondary drugs for overcoming drug resistance.
PMID- 27490095
TI - Characterization of Portal Vein Thrombosis (Neoplastic Versus Bland) on CT Images
Using Software-Based Texture Analysis and Thrombus Density (Hounsfield Units).
AB - OBJECTIVE: The purpose of this study was to investigate the role of CT texture
analysis and thrombus density (measured in Hounsfield units) in distinguishing
between neoplastic and bland portal vein thrombosis (PVT) on portal venous phase
CT. MATERIALS AND METHODS: In this retrospective study, 117 contrast-enhanced CT
studies of 109 patients were included for characterization of PVT. Assessment of
PVT was performed by estimation of CT textural features using CT texture analysis
software and measurement of attenuation values. For CT texture analysis, filtered
and unfiltered images were assessed to quantify heterogeneity using a set of
predefined histogram-based texture parameters. The Mann-Whitney U test and binary
logistic regression were applied for statistical significance. ROC curves were
used to identify accuracy and optimal cutoff values. RESULTS: Of the 117 CT
studies, 63 neoplastic thrombi and 54 bland thrombi were identified on the
images. The two most discriminative CT texture analysis parameters to
differentiate neoplastic from bland thrombus were mean value of positive pixels
(without filtration, p < 0.001) and entropy (with fine filtration, p < 0.001).
Mean thrombus density values could also reliably distinguish neoplastic (81.39
HU) and bland (32.88 HU) thrombi (p < 0.001). The AUCs were 0.97 for mean value
of positive pixels (p < 0.001), 0.93 for entropy (p < 0.001), 0.99 for the model
combining mean value of positive pixels and entropy (p < 0.001), 0.91 for
thrombus density (p < 0.001), and 0.61 for the radiologist's subjective
evaluation (p = 0.037). The optimal cutoffs values were 56.9 for mean value of
positive pixels, 4.50 for entropy, and 54.0 HU for thrombus density. CONCLUSION:
CT texture analysis and CT attenuation values allow reliable differentiation
between neoplastic and bland thrombi on a single portal venous phase CT
examination.
PMID- 27490096
TI - Influence of Gas Adsorption and Gold Nanoparticles on the Electrical Properties
of CVD-Grown MoS2 Thin Films.
AB - Molybdenum disulfide (MoS2) has increasingly attracted attention from researchers
and is now one of the most intensively explored atomic-layered two-dimensional
semiconductors. Control of the carrier concentration and doping type of MoS2 is
crucial for its application in electronic and optoelectronic devices. Because the
MoS2 layers are atomically thin, their transport characteristics may be very
sensitive to ambient gas adsorption and the resulting charge transfer. We
investigated the influence of the ambient gas (N2, H2/N2, and O2) choice on the
resistance (R) and surface work function (WF) of trilayer MoS2 thin films grown
via chemical vapor deposition. We also studied the electrical properties of gold
(Au)-nanoparticle (NP)-coated MoS2 thin films; their R value was found to be 2
orders of magnitude smaller than that for bare samples. While the WF largely
varied for each gas, R was almost invariant for both the bare and Au-NP-coated
samples regardless of which gas was used. Temperature-dependent transport
suggests that variable range hopping is the dominant mechanism for electrical
conduction for bare and Au-NP-coated MoS2 thin films. The charges transferred
from the gas adsorbates might be insufficient to induce measurable R change
and/or be trapped in the defect states. The smaller WF and larger localization
length of the Au-NP-coated sample, compared with the bare sample, suggest that
more carriers and less defects enhanced conduction in MoS2.
PMID- 27490094
TI - Translesion Synthesis of the N(2)-2'-Deoxyguanosine Adduct of the Dietary Mutagen
IQ in Human Cells: Error-Free Replication by DNA Polymerase kappa and Mutagenic
Bypass by DNA Polymerases eta, zeta, and Rev1.
AB - Translesion synthesis (TLS) of the N(2)-2'-deoxyguanosine (dG-N(2)-IQ) adduct of
the carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was investigated in
human embryonic kidney 293T cells by replicating plasmid constructs in which the
adduct was individually placed at each guanine (G1, G2, or G3) of the NarI
sequence (5'-CG1G2CG3CC-3'). TLS efficiency was 38%, 29%, and 25% for the dG-N(2)
IQ located at G1, G2, and G3, respectively, which suggests that dG-N(2)-IQ is
bypassed more efficiently by one or more DNA polymerases at G1 than at either G2
or G3. TLS efficiency was decreased 8-35% in cells with knockdown of pol eta, pol
kappa, pol iota, pol zeta, or Rev1. Up to 75% reduction in TLS occurred when pol
eta, pol zeta, and Rev1 were simultaneously knocked down, suggesting that these
three polymerases play important roles in dG-N(2)-IQ bypass. Mutation frequencies
(MFs) of dG-N(2)-IQ at G1, G2, and G3 were 23%, 17%, and 11%, respectively,
exhibiting a completely reverse trend of the previously reported MF of the C8-dG
adduct of IQ (dG-C8-IQ), which is most mutagenic at G3 ( ( 2015 ) Nucleic Acids
Res. 43 , 8340 - 8351 ). The major type of mutation induced by dG-N(2)-IQ was
targeted G -> T, as was reported for dG-C8-IQ. In each site, knockdown of pol
kappa resulted in an increase in MF, whereas MF was reduced when pol eta, pol
iota, pol zeta, or Rev1 was knocked down. The reduction in MF was most pronounced
when pol eta, pol zeta, and Rev1 were simultaneously knocked down and especially
when the adduct was located at G3, where MF was reduced by 90%. We conclude that
pol kappa predominantly performs error-free TLS of the dG-N(2)-IQ adduct, whereas
pols eta, pol zeta, and Rev1 cooperatively carry out the error-prone TLS.
However, in vitro experiments using yeast pol zeta and kappa showed that the
former was inefficient in full-length primer extension on dG-N(2)-IQ templates,
whereas the latter was efficient in both error-free and error-prone extensions.
We believe that the observed differences between the in vitro experiments using
purified DNA polymerases, and the cellular results may arise from several factors
including the crucial roles played by the accessory proteins in TLS.
PMID- 27490097
TI - Combinatorial Solid-Phase Synthesis and Biological Evaluation of
Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology.
AB - Combinatorial synthesis and biological evaluation of cyclodepsipeptide destruxin
B have been achieved. The cyclization precursors were prepared by solid-phase
peptide synthesis via a split and pool method utilizing SynPhase lanterns with
colored tags and cogs, followed by cleavage from the polymer-support.
Macrolactonization utilizing MNBA-DMAPO in solution-phase was successfully
performed in parallel to afford the desired 64-member destruxin analogues in
moderate to good yields. Biological evaluation of the synthesized analogues
indicated that a MeAla residue for the building block A is required to induce the
desired morphological changes in osteoclast-like multinuclear cells (OCLs), and
introduction of the substituent at the R(4) position of a proline moiety is
tolerated by the morphology and may enable the preparation of a molecular probe
for the target identification in the osteoclasts.
PMID- 27490098
TI - A Systematic Review of Randomized Controlled Trials on Oral Chinese Herbal
Medicine for Prostate Cancer.
AB - BACKGROUND: Prostate cancer is the most common malignant tumor associated with
male reproductive system. OBJECTIVE: The existing eligible randomized controlled
trials (RCTs) were critically appraised for the safety and effectiveness of CHM
for prostate cancer. METHODS: A literature search was conducted by using PubMed,
CENTRAL, CNKI, CBM, VIP and Wanfang databases until August 2015. RCTs of CHM or
CHM plus conventional medicine for prostate cancer patients were included. The
primary outcomes appraised were survival time, time to progression and quality of
life. The risk of bias assessment according to the Cochrane Handbook was used to
evaluate the methodological quality of the included trials. Revman 5.3 software
was used for data analyses. Risk ratio and mean difference (MD) with a 95%
confidence interval (CI) were used as effect measures. Meta-analysis was to be
used if sufficient trials without obvious clinical or statistical heterogeneity
were available. RESULTS: A total of 17 RCTs involving 1224 participants were
analyzed. One trial was about CHM comparing to no treatment. The remaining 16
trials used CHMs as adjunctive treatment for endocrine therapy. Due to the poor
quality of methodologies of most trials, only limited evidence showed that a
combination of CHM and endocrine therapy might be more effective in restraining
the development of the disease (MD 10.37 months, 95%CI 9.10 to 11.63 months),
increasing patients' survival time (7-15 months) or improving patients'
performance status, when compared to endocrine therapy alone (Karnofsky
performance scale average changed 15 scores between groups). No severe adverse
event was reported related to CHM. CONCLUSION: Due to the insufficient quality of
trials that were analyzed, it is not appropriate to recommend any kind of CHMs in
treating prostate cancer at the present time. Well-designed trials with high
methodological quality are needed to validate the effect of CHMs for patients
with prostate cancer.
PMID- 27490099
TI - Identification of Novel Smoothened Ligands Using Structure-Based Docking.
AB - The seven transmembrane protein Smoothened is required for Hedgehog signaling
during embryonic development and adult tissue homeostasis. Inappropriate
activation of the Hedgehog signalling pathway leads to cancers such as basal cell
carcinoma and medulloblastoma, and Smoothened inhibitors are now available
clinically to treat these diseases. However, resistance to these inhibitors
rapidly develops thereby limiting their efficacy. The determination of Smoothened
crystal structures enables structure-based discovery of new ligands with new
chemotypes that will be critical to combat resistance. In this study, we docked
3.2 million available, lead-like molecules against Smoothened, looking for those
with high physical complementarity to its structure; this represents the first
such campaign against the class Frizzled G-protein coupled receptor family.
Twenty-one high-ranking compounds were selected for experimental testing, and
four, representing three different chemotypes, were identified to antagonize
Smoothened with IC50 values better than 50 MUM. A screen for analogs revealed
another six molecules, with IC50 values in the low micromolar range. Importantly,
one of the most active of the new antagonists continued to be efficacious at the
D473H mutant of Smoothened, which confers clinical resistance to the antagonist
vismodegib in cancer treatment.
PMID- 27490101
TI - Subcutaneous Immunoglobulin Therapy in the Chronic Management of Myasthenia
Gravis: A Retrospective Cohort Study.
AB - BACKGROUND: Immunoglobulin therapy has become a major treatment option in several
autoimmune neuromuscular disorders. For patients with Myasthenia Gravis (MG),
intravenous immunoglobulin (IVIg) has been used for both crisis and chronic
management. Subcutaneous Immunoglobulins (SCIg), which offer the advantage of
home administration, may be a practical and effective option in chronic
management of MG. We analyzed clinical outcomes and patient satisfaction in nine
cases of chronic disabling MG who were either transitioned to, or started de novo
on SCIg. METHODS AND FINDINGS: This was a retrospective cohort study for the
period of 2015-2016, with a mean follow-up period of 6.8 months after initiation
of SCIg. All patients with MG treated with SCIg at the Ottawa Hospital, a large
Canadian tertiary hospital with subspecialty expertise in neuromuscular disorders
were included, regardless of MG severity, clinical subtype and antibody status.
The primary outcome was MG disease activity after SCIg initiation. This outcome
was measured by 1) the Myasthenia Gravis Foundation of America (MGFA) clinical
classification, and 2) subjective scales of disease activity including the
Myasthenia Gravis activities of daily living profile (MG-ADL), Myasthenia Gravis
Quality-of-life (MG-QOL 15), Visual Analog (VA) satisfaction scale. We also
assessed any requirement for emergency department visits or hospitalizations.
Safety outcomes included any SCIg related complication. All patients were stable
or improved for MGFA class after SCIg initiation. Statistically significant
improvements were documented in the MG-ADL, MG-QOL and VAS scales. There were no
exacerbations after switching therapy and no severe SCIg related complications.
CONCLUSIONS: SCIg may be a beneficial therapy in the chronic management of MG,
with favorable clinical outcome and patient satisfaction results.
PMID- 27490100
TI - Early Fungicidal Activity as a Candidate Surrogate Endpoint for All-Cause
Mortality in Cryptococcal Meningitis: A Systematic Review of the Evidence.
AB - BACKGROUND: Cryptococcal meningitis (CM) is a leading cause of HIV-associated
mortality. In clinical trials evaluating treatments for CM, biomarkers of early
fungicidal activity (EFA) in cerebrospinal fluid (CSF) have been proposed as
candidate surrogate endpoints for all- cause mortality (ACM). However, there has
been no systematic evaluation of the group-level or trial-level evidence for EFA
as a candidate surrogate endpoint for ACM. METHODS: We conducted a systematic
review of randomized trials in treatment of CM to evaluate available evidence for
EFA measured as culture negativity at 2 weeks/10 weeks and slope of EFA as
candidate surrogate endpoints for ACM. We performed sensitivity analysis on
superiority trials and high quality trials as determined by Cochrane measures of
trial bias. RESULTS: Twenty-seven trials including 2854 patients met inclusion
criteria. Mean ACM was 15.8% at 2 weeks and 27.0% at 10 weeks with no overall
significant difference between test and control groups. There was a statistically
significant group-level correlation between average EFA and ACM at 10 weeks but
not at 2 weeks. There was also no statistically significant group-level
correlation between CFU culture negativity at 2weeks/10weeks or average EFA slope
at 10 weeks. A statistically significant trial-level correlation was identified
between EFA slope and ACM at 2 weeks, but is likely misleading, as there was no
treatment effect on ACM. CONCLUSIONS: Mortality remains high in short time
periods in CM clinical trials. Using published data and Institute of Medicine
criteria, evidence for use of EFA as a surrogate endpoint for ACM is insufficient
and could provide misleading results from clinical trials. ACM should be used as
a primary endpoint evaluating treatments for cryptococcal meningitis.
PMID- 27490102
TI - Salicylic Acid and Sodium Salicylate Alleviate Cadmium Toxicity to Different
Extents in Maize (Zea mays L.).
AB - The role of salicylic acid in Cd tolerance has attracted more attention recently
but no information is available on the efficiency of different forms of salicylic
acid. The aim was thus to investigate whether both the acid and salt forms of
salicylic acid provide protection against Cd stress and to compare their mode of
action. Young maize plants were grown under controlled environmental conditions.
One group of 10-day-old seedlings were treated with 0.5 mM SA or NaSA for 1 day
then half of the pants were treated with 0.5 mM Cd for 1 day. Another group of
seedlings was treated with 0.5 mM CdSO4 for 1 day without pre-treatment with SA
or NaSA, while a third group was treated simultaneously with Cd and either SA or
NaSA. Both salicylic acid forms reduced the Cd accumulation in the roots.
Treatment with the acidic form meliorated the Cd accumulation in the leaves,
while Na-salicylate increased the phytochelatin level in the roots and the amount
of salicylic acid in the leaves. Furthermore, increased antioxidant enzyme
activity was mainly induced by the acid form, while glutathione-related redox
changes were influenced mostly by the salt form. The acidic and salt forms of
salicylic acid affected the two antioxidant systems in different ways, and the
influence of these two forms on the distribution and detoxification of Cd also
differed. The present results also draw attention to the fact that
generalisations about the stress protective mechanisms induced by salicylic acid
are misleading since different forms of SA may exert different effects on the
plants via separate mechanisms.
PMID- 27490104
TI - Selective Data Analysis in Brown et al.'s Continued Critical Reanalysis.
PMID- 27490103
TI - Co-Administration of Soy Isoflavones and Vitamin D in Management of Irritable
Bowel Disease.
AB - BACKGROUND AND AIMS: The substantial characteristics of Irritable Bowel Syndrome
(IBS) are associated with estrogens in women. Both soy isoflavones and vitamin D
can modulate estrogen receptors in the colonic smooth muscles. The aim of this
study was to investigate the effects of soy isoflavones, vitamin D and their
probable interactions in women with IBS. METHODS: In a factorial blinded
randomized clinical trial, 100 women with IBS (age:18-75yr, were randomly
assigned in 4 arms to receive either placebo of vitamin D and placebo of soy
isoflavones (P+P), or placebo of vitamin D and soy isoflavones (P+S), or vitamin
D and placebo of soy isoflavones (D+P), or vitamin D and soy isoflavones (D+S)
for 6 weeks. Dosage of soy isoflavone was 2 capsules of 20 mg soy isoflavones per
day, and dosage of vitamin D was one pearl of 50'000 IU biweekly. The clinical
outcomes were IBS symptoms severity scores (IBS-SSS), disease- specific quality
of life (IBS-QOL) and total score (IBS-TS) that evaluated at weeks 0, 6, and 10,
and compared to each other. RESULTS: IBS-TS improved significantly in both S+P
and D+P groups (p- value = 0.004, 0.015). The interaction effect of soy
isoflavones and vitamin D on IBS-TS was significant (p<0.05). The interaction
effect of soy isoflavones with vitamin D and the main effect of vitamin D on IBS
SSS were not statistically significant, whereas IBS-SSS decreased significantly
in S+P and D+P groups (p-value = 0.001, 0.047 respectively). CONCLUSION: Our
results indicate that co-administration of soy isoflavones with vitamin D did not
improve the IBS- SSS and IBS- QOL; however, it improved the IBS-TS. TRIAL
REGISTRATION: Clinical Trials.gov NCT02026518.
PMID- 27490105
TI - CONGENITAL CYSTIC LUNG LESIONS: EVOLUTION FROM IN-UTERO TO PATHOLOGY DIAGNOSIS -
A MULTIDISCIPLINARY APPROACH.
AB - Congenital cystic lung lesions (CCLL) are a group of rare pathologies that are
usually diagnosed in the pre-natal period. The majority of these lesions are
diagnosed at pathology examination as congenital pulmonary airway malformations
(CPAM) and bronchopulmonary sequestration (BPS). These lesions are typically
managed by surgical intervention within the first year of life and have an
excellent prognosis. We examined the evolution of imaging appearances from
prenatal diagnosis to postnatal work-up of these lesions and correlate imaging
and pathological findings. An 8-year retrospective review of the perinatal and
pathology database of a single tertiary care center identified 42 cases of CCLL
of which 36 had known prenatal ultrasound and prenatal course available. Final
pathologic diagnoses were: 15 CPAM (41%), 7 BPS (19%) and 9 hybrid BPS and CPAM
lesions (25%). Five cases with bronchial atresia were also identified (either in
isolation or associated with CPAM or BPS). The overall characteristics of these
lesions by prenatal ultrasound, postnatal imaging, and ultimate histopathologic
diagnosis are described.
PMID- 27490106
TI - Identifying the topology of signaling networks from partial RNAi data.
AB - BACKGROUND: Methods for inferring signaling networks using single gene knockdown
RNAi experiments and reference networks have been proposed in recent years. These
methods assume that RNAi information is available for all the genes in the signal
transduction pathway, i.e., complete. This assumption does not always hold up
since RNAi experiments are often incomplete and information for some genes is
missing. RESULTS: In this article, we develop two methods to construct signaling
networks from incomplete RNAi data with the help of a reference network. These
methods infer the RNAi constraints for the missing genes such that the inferred
network is closest to the reference network. We perform extensive experiments
with both real and synthetic networks and demonstrate that these methods produce
accurate results efficiently. CONCLUSIONS: Application of our methods to Wnt
signal transduction pathway has shown that our methods can be used to construct
highly accurate signaling networks from experimental data in less than 100 ms.
The two methods that produce accurate results efficiently show great promise of
constructing real signaling networks.
PMID- 27490107
TI - Rh-Catalyzed [3 + 2] Cycloaddition of 1-Sulfonyl-1,2,3-triazoles: Access to the
Framework of Aspidosperma and Kopsia Indole Alkaloids.
AB - A Rh(II)-catalyzed dearomative intramolecular [3 + 2] dipolar cycloaddition
involving the indolic C2-C3 carbon-carbon double bond has been developed. The
reaction was launched from the triazole moiety within the substrate and proceeded
efficiently under mild conditions. A wide range of functional groups could be
tolerated. These features render the current reaction a highly useful tool for
the synthesis of polycyclic indole alkaloids, as showcased by a rapid assembly of
the core structure of Aspidosperma and the related alkaloids.
PMID- 27490108
TI - The Virtuous Cycle of a Data Ecosystem.
PMID- 27490110
TI - Metagenomic Analysis of Fungal Diversity on Strawberry Plants and the Effect of
Management Practices on the Fungal Community Structure of Aerial Organs.
AB - An amplicon metagenomic approach based on the ITS2 region of fungal rDNA was used
to identify the composition of fungal communities associated with different
strawberry organs (leaves, flowers, immature and mature fruits), grown on a farm
using management practices that entailed the routine use of various chemical
pesticides. ITS2 sequences clustered into 316 OTUs and Ascomycota was the
dominant phyla (95.6%) followed by Basidiomycota (3.9%). Strawberry plants
supported a high diversity of microbial organisms, but two genera, Botrytis and
Cladosporium, were the most abundant, representing 70-99% of the relative
abundance (RA) of all detected sequences. According to alpha and beta diversity
analyses, strawberry organs displayed significantly different fungal communities
with leaves having the most diverse fungal community, followed by flowers, and
fruit. The interruption of chemical treatments for one month resulted in a
significant modification in the structure of the fungal community of leaves and
flowers while immature and mature fruit were not significantly affected. Several
plant pathogens of other plant species, that would not be intuitively expected to
be present on strawberry plants such as Erysiphe, were detected, while some
common strawberry pathogens, such as Rhizoctonia, were less evident or absent.
PMID- 27490109
TI - A Proteomic Investigation of Hepatic Resistance to Ascaris in a Murine Model.
AB - The helminth Ascaris causes ascariasis in both humans and pigs. Humans,
especially children, experience significant morbidity including respiratory
complications, growth deficits and intestinal obstruction. Given that 800 million
people worldwide are infected by Ascaris, this represents a significant global
public health concern. The severity of the symptoms and associated morbidity are
related to the parasite burden and not all hosts are infected equally. While the
pathology of the disease has been extensively examined, our understanding of the
molecular mechanisms underlying resistance and susceptibility to this nematode
infection is poor. In order to investigate host differences associated with heavy
and light parasite burden, an experimental murine model was developed utilising
Ascaris-susceptible and -resistant mice strains, C57BL/6J and CBA/Ca,
respectively, which experience differential burdens of migratory Ascaris larvae
in the host lungs. Previous studies identified the liver as the site where this
difference in susceptibility occurs. Using a label free quantitative proteomic
approach, we analysed the hepatic proteomes of day four post infection C57BL/6J
and CBA/Ca mice with and without Ascaris infection to identify proteins changes
potentially linked to both resistance and susceptibility amongst the two strains,
respectively. Over 3000 proteins were identified in total and clear intrinsic
differences were elucidated between the two strains. These included a higher
abundance of mitochondrial proteins, particularly those associated with the
oxidative phosphorylation pathway and reactive oxygen species (ROS) production in
the relatively resistant CBA/Ca mice. We hypothesise that the increased ROS
levels associated with higher levels of mitochondrial activity results in a
highly oxidative cellular environment that has a dramatic effect on the
nematode's ability to successfully sustain a parasitic association with its
resistant host. Under infection, both strains had increased abundances in
proteins associated with the oxidative phosphorylation pathway, as well as the
tricarboxylic acid cycle, with respect to their controls, indicating a general
stress response to Ascaris infection. Despite the early stage of infection, some
immune-associated proteins were identified to be differentially abundant,
providing a novel insight into the host response to Ascaris. In general, the
susceptible C57BL/6J mice displayed higher abundances in immune-associated
proteins, most likely signifying a more active nematode cohort with respect to
their CBA/Ca counterparts. The complement component C8a and S100 proteins, S100a8
and S100a9, were highly differentially abundant in both infected strains,
signifying a potential innate immune response and the importance of the
complement pathway in defence against macroparasite infection. In addition, the
signatures of an early adaptive immune response were observed through the
presence of proteins, such as plastin-2 and dipeptidyl peptidase 1. A marked
decrease in proteins associated with translation was also observed in both
C57BL/6J and CBA/Ca mice under infection, indicative of either a general response
to Ascaris or a modulatory effect by the nematode itself. Our research provides
novel insights into the in vivo host-Ascaris relationship on the molecular level
and provides new research perspectives in the development of Ascaris control and
treatment strategies.
PMID- 27490111
TI - Adrenal Hormone and Metabolic Biomarker Responses to 30 min of Intermittent
Cycling Exercise in Breast Cancer Survivors.
AB - The aim of this study was to explore the effect of one bout of aerobic exercise
on epinephrine, norepinephrine, cortisol, glucose, lactate, and free fatty acid
(FFA) responses in breast cancer survivors and healthy controls. 9 female breast
cancer survivors and 9 women without a history of cancer completed 30 min of
cycle ergometry exercise at 60% of VO2peak. Blood samples were taken pre
exercise, immediately post-exercise, and 2 h post-exercise from which plasma
concentrations of study variables were measured. Immediately and 2 h post
exercise, increases were observed in epinephrine (control group only)
norepinephrine (both groups), lactate (both groups), and FFA (both groups
immediately post-exercise; breast cancer survivor group only at 2 h post
exercise) (p<0.05). Cortisol decreased immediately and 2 h post-exercise in the
control group while glucose decreased immediately post-exercise in the breast
cancer survivor group (p<0.05). In conclusion, breast cancer survivors appeared
to display attenuated epinephrine, cortisol, and lactate responses while
displaying larger magnitude changes in glucose and FFA responses compared to
controls. These preliminary findings may have implications for the regulation of
metabolism during exercise in breast cancer survivors.
PMID- 27490112
TI - The Role of Body Habitus in Predicting Cardiorespiratory Fitness: The FRIEND
Registry.
AB - This study aimed to validate and cross-validate a non-exercise prediction model
from a large and apparently healthy US cohort of individuals who underwent an
analysis of body habitus (waist circumference (WC) and body mass index (BMI))
with measured CRF. The large cohort (5 030 individuals) was split into validation
(4 030) and cross-validation (1 000) groups, whereby waist circumference and
maximal aerobic capacity (VO2max) were assessed by rigorously approved
laboratories. VO2max was estimated in 2 multiple regression equations using age,
sex and either WC (r=0.77; standard error of the estimate (SEE) 6.70 mLO2?kg(
1)?min(-1)) or BMI (r=0.76; SEE 6.89 mLO2?kg(-1)?min(-1)).Cross-validation
yielded similar results. However, as VO2max increased, there was increased bias,
suggesting VO2max may be underestimated at higher values. Both WC and BMI
prediction models yielded similar findings, with WC having a slightly smaller
SEE. These measures of body habitus appear to be adequate in predicting CRF using
non-exercise parameters, even without a measure of physical activity. Caution
should be taken when using these equations in more fit individuals.
PMID- 27490113
TI - Modeling the prevention of colorectal cancer from the combined impact of host and
behavioral risk factors.
AB - PURPOSE: This study investigated the utility of modeling modifiable lifestyle
risk factors in addition to genetic variation in colorectal cancer (CRC)
screening/prevention. METHODS: We derived a polygenic risk score for CRC
susceptibility variants in combination with the established nongenetic risk
factors of inflammatory bowel disease (IBD), adiposity, alcohol, red meat, fruit,
vegetables, smoking, physical activity, and aspirin. We used the 37 known risk
variants and 50 and 100% of all risk variants as calculated from a heritability
estimate. We derived absolute risk from UK population age structure, incidence,
and mortality rate data. RESULTS: Taking into account all risk factors (known
variants), 42.2% of 55- to 59-year-old men with CRC have a risk at least as high
as that of an average 60-year-old, the minimum eligible age for the UK NHS
National Bowel Cancer Screening Program. If the male population is stratified by
known variants and IBD status, then risk-difference estimates imply that for
10,000 50-year-old men in the 99th percentile, 760 cases could be prevented over
a 25-year period through the modifiable risk factors, but in the lowest
percentile, only 90 could be prevented. CONCLUSION: CRC screening and prevention
centered on modifiable risk factors could be optimized if targeted at individuals
at higher polygenic risk.Genet Med 19 3, 314-321.
PMID- 27490114
TI - Is "incidental finding" the best term?: a study of patients' preferences.
AB - PURPOSE: There is debate within the genetics community about the optimal term to
describe genetic variants unrelated to the test indication but potentially
important for health. Given the lack of consensus and the importance of adopting
terminology that promotes effective clinical communication, we sought the opinion
of clinical genetics patients. METHODS: Surveys and focus groups with two patient
populations were conducted. Eighty-eight survey participants were asked to rank
four terms according to how well each describes results unrelated to the test
indication: incidental findings, secondary findings, additional findings, and
ancillary findings. Participants in six focus groups were guided through a free
thought exercise to describe the desired attributes of such a term and then asked
to formulate the best term to represent this concept. RESULTS: The term
additional findings had the most first-choice rankings by survey participants,
followed by secondary findings, incidental findings, and ancillary findings. Most
focus group participants preferred the term additional findings; they also gave
reasons why other terms were not optimal. CONCLUSION: Additional findings was
preferred because it was more neutral and accessible than other terms currently
in use. Patient perceptions and comprehension will be framed by the terminology
used by healthcare providers. Thus, patient opinions should be considered by
medical genetics professionals.Genet Med 19 2, 176-181.
PMID- 27490116
TI - Distributive justice, diversity, and inclusion in precision medicine: what will
success look like?
PMID- 27490115
TI - NR5A1 is a novel disease gene for 46,XX testicular and ovotesticular disorders of
sex development.
AB - PURPOSE: We aimed to identify the genetic cause in a cohort of 11 unrelated cases
and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex
development (DSD). METHODS: Whole-exome sequencing (n = 9), targeted resequencing
(n = 4), and haplotyping were performed. Immunohistochemistry of sex-specific
markers was performed on patients' gonads. The consequences of mutation were
investigated using luciferase assays, localization studies, and RNA-seq. RESULTS:
We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in
three unrelated patients. The Arg92 residue is highly conserved and located in
the Ftz-F1 region, probably involved in DNA-binding specificity and stability.
There were no consistent changes in transcriptional activation or subcellular
localization. Transcriptomics in patient-derived lymphocytes showed upregulation
of MAMLD1, a direct NR5A1 target previously associated with 46,XY DSD. In gonads
of affected individuals, ovarian FOXL2 and testicular SRY-independent SOX9
expression observed. CONCLUSIONS: We propose NR5A1, previously associated with
46,XY DSD and 46,XX primary ovarian insufficiency, as a novel gene for 46,XX
(ovo)testicular DSD. We hypothesize that p.(Arg92Trp) results in decreased
inhibition of the male developmental pathway through downregulation of female
antitestis genes, thereby tipping the balance toward testicular differentiation
in 46,XX individuals. In conclusion, our study supports a role for NR5A1 in
testis differentiation in the XX gonad.Genet Med 19 4, 367-376.
PMID- 27490117
TI - Contraceptive Use Among Nonpregnant and Postpartum Women at Risk for Unintended
Pregnancy, and Female High School Students, in the Context of Zika Preparedness -
United States, 2011-2013 and 2015.
AB - Zika virus infection during pregnancy can cause congenital microcephaly and brain
abnormalities (1,2). Since 2015, Zika virus has been spreading through much of
the World Health Organization's Region of the Americas, including U.S.
territories. Zika virus is spread through the bite of Aedes aegypti or Aedes
albopictus mosquitoes, by sex with an infected partner, or from a pregnant woman
to her fetus during pregnancy.* CDC estimates that 41 states are in the potential
range of Aedes aegypti or Aedes albopictus mosquitoes (3), and on July 29, 2016,
the Florida Department of Health identified an area in one neighborhood of Miami
where Zika virus infections in multiple persons are being spread by bites of
local mosquitoes. These are the first known cases of local mosquito-borne Zika
virus transmission in the continental United States.(?) CDC prevention efforts
include mosquito surveillance and control, targeted education about Zika virus
and condom use to prevent sexual transmission, and guidance for providers on
contraceptive counseling to reduce unintended pregnancy. To estimate the
prevalence of contraceptive use among nonpregnant and postpartum women at risk
for unintended pregnancy and sexually active female high school students living
in the 41 states where mosquito-borne transmission might be possible, CDC used
2011-2013 and 2015 survey data from four state-based surveillance systems: the
Behavioral Risk Factor Surveillance System (BRFSS, 2011-2013), which surveys
adult women; the Pregnancy Risk Assessment Monitoring System (PRAMS, 2013) and
the Maternal and Infant Health Assessment (MIHA, 2013), which surveys women with
a recent live birth; and the Youth Risk Behavior Survey (YRBS, 2015), which
surveys students in grades 9-12. CDC defines an unintended pregnancy as one that
is either unwanted (i.e., the pregnancy occurred when no children, or no more
children, were desired) or mistimed (i.e., the pregnancy occurred earlier than
desired). The proportion of women at risk for unintended pregnancy who used a
highly effective reversible method, known as long-acting reversible contraception
(LARC), ranged from 5.5% to 18.9% for BRFSS-surveyed women and 6.9% to 30.5% for
PRAMS/MIHA-surveyed women. The proportion of women not using any contraception
ranged from 12.3% to 34.3% (BRFSS) and from 3.5% to 15.3% (PRAMS/MIHA). YRBS data
indicated that among sexually active female high school students, use of LARC at
last intercourse ranged from 1.7% to 8.4%, and use of no contraception ranged
from 7.3% to 22.8%. In the context of Zika preparedness, the full range of
contraceptive methods approved by the Food and Drug Administration (FDA),
including LARC, should be readily available and accessible for women who want to
avoid or delay pregnancy. Given low rates of LARC use, states can implement
strategies to remove barriers to the access and availability of LARC including
high device costs, limited provider reimbursement, lack of training for providers
serving women and adolescents on insertion and removal of LARC, provider lack of
knowledge and misperceptions about LARC, limited availability of youth-friendly
services that address adolescent confidentiality concerns, inadequate client
centered counseling, and low consumer awareness of the range of contraceptive
methods available.
PMID- 27490119
TI - Expanding Host Range and Cross-Species Infection of Hepatitis E Virus.
PMID- 27490118
TI - HIF-2alpha Expression Regulates Sprout Formation into 3D Fibrin Matrices in
Prolonged Hypoxia in Human Microvascular Endothelial Cells.
AB - BACKGROUND: During short-term hypoxia, Hypoxia Inducible Factors (particular
their subunits HIF-1alpha and HIF-2alpha) regulate the expression of many genes
including the potent angiogenesis stimulator VEGF. However, in some pathological
conditions chronic hypoxia occurs and is accompanied by reduced angiogenesis.
OBJECTIVES: We investigated the effect of prolonged hypoxia on the proliferation
and sprouting ability of human microvascular endothelial cells and the
involvement of the HIFs and Dll4/Notch signaling. METHODS AND RESULTS: Human
microvascular endothelial cells (hMVECs), cultured at 20% oxygen for 14 days and
seeded on top of 3D fibrin matrices, formed sprouts when stimulated with VEGF
A/TNFalpha. In contrast, hMVECs precultured at 1% oxygen for 14 days were viable
and proliferative, but did not form sprouts into fibrin upon VEGF-A/TNFalpha
stimulation at 1% oxygen. Silencing of HIF-2alpha with si-RNA partially restored
the inhibition of endothelial sprouting, whereas HIF-1alpha or HIF-3alpha by si
RNA had no effect. No involvement of Dll4/Notch pathway in the inhibitory effect
on endothelial sprouting by prolonged hypoxia was found. In addition, hypoxia
decreased the production of urokinase-type plasminogen activator (uPA), needed
for migration and invasion, without a significant effect on its inhibitor PAI-1.
This was independent of HIF-2alpha, as si-HIF-2alpha did not counteract uPA
reduction. CONCLUSION: Prolonged culturing of hMVECs at 1% oxygen inhibited
endothelial sprouting into fibrin. Two independent mechanisms contribute.
Silencing of HIF-2alpha with si-RNA partially restored the inhibition of
endothelial sprouting pointing to a HIF-2alpha-dependent mechanism. In addition,
reduction of uPA contributed to reduced endothelial tube formation in a fibrin
matrix during prolonged hypoxia.
PMID- 27490120
TI - Prediction of scaffold proteins based on protein interaction and domain
architectures.
AB - BACKGROUND: Scaffold proteins are known for being crucial regulators of various
cellular functions by assembling multiple proteins involved in signaling and
metabolic pathways. Identification of scaffold proteins and the study of their
molecular mechanisms can open a new aspect of cellular systemic regulation and
the results can be applied in the field of medicine and engineering. Despite
being highlighted as the regulatory roles of dozens of scaffold proteins, there
was only one known computational approach carried out so far to find scaffold
proteins from interactomes. However, there were limitations in finding diverse
types of scaffold proteins because their criteria were restricted to the
classical scaffold proteins. In this paper, we will suggest a systematic approach
to predict massive scaffold proteins from interactomes and to characterize the
roles of scaffold proteins comprehensively. RESULTS: From a total of 10,419 basic
scaffold protein candidates in protein interactomes, we classified them into
three classes according to the structural evidences for scaffolding, such as
domain architectures, domain interactions and protein complexes. Finally, we
could define 2716 highly reliable scaffold protein candidates and their
characterized functional features. To assess the accuracy of our prediction, the
gold standard positive and negative data sets were constructed. We prepared 158
gold standard positive data and 844 gold standard negative data based on the
functional information from Gene Ontology consortium. The precision, sensitivity
and specificity of our testing was 80.3, 51.0, and 98.5 % respectively. Through
the function enrichment analysis of highly reliable scaffold proteins, we could
confirm the significantly enriched functions that are related to scaffold protein
binding. We also identified functional association between scaffold proteins and
their recruited proteins. Furthermore, we checked that the disease association of
scaffold proteins is higher than kinases. CONCLUSIONS: In conclusion, we could
predict larger volume of scaffold proteins and analyzed their functional
characteristics. Deeper understandings about the roles of scaffold proteins from
this study will provide a higher opportunity to find therapeutic or engineering
applications of scaffold proteins using their functional characteristics.
PMID- 27490121
TI - Surface Sites in Cu-Nanoparticles: Chemical Reactivity or Microscopy?
AB - Copper nanoparticles are widely used in catalysis and electrocatalysis, and the
fundamental understanding of their activity requires reliable methods to assess
the number of potentially reactive atoms exposed on the surface. Herein, we
provide a molecular understanding of the difference observed in addressing
surface site titration using prototypical methods: transmission electron
micrscopy (TEM), H2 chemisorption, and N2O titration by a combination of
experimental and theoretical study. We show in particular that microscopy does
not allow assessing the amount of reactive surface sites, while H2 and N2O
chemisorptions can, albeit with slightly different stoichiometries (1 O/2CuS and
1 H2/2.2CuS), which can be rationalized by density functional theory
calculations. High-resolution TEM shows that the origin of the observed
difference between microscopy and titration methods is due to the strong metal
support interaction experienced by small copper nanoparticles with the silica
surface.
PMID- 27490122
TI - The rich and the poor: environmental biodiversity protecting from allergy.
AB - PURPOSE OF REVIEW: It has been proposed that biodiversity loss leads to reduced
interaction between environmental and human microbiotas. This, in turn, may lead
to immune dysfunction and impaired tolerance mechanisms in humans. That is,
contact with environmental biodiversity is expected to protect from allergies.
However, direct evidence linking contact with biodiversity and risk of allergy
has been lacking. In this review, we consider the latest research on the
biodiversity hypothesis of allergy. RECENT FINDINGS: It is becoming clear that
what you eat, drink, inhale, and touch all contribute to the grand scheme of host
microbial crosstalk that is needed for a balanced, healthy immune system to
develop and maintain a healthy recognition between harmful and harmless
invasions. Microbes can either communicate directly with host immune cells or
affect the host via metabolism that can even lead to epigenetic modifications.
Our living environment plays a key role in this process. Although especially,
early exposure to diverse, beneficial microbiota from the environment is
repeatedly found crucial, studies on immigrants demonstrate that condition in
later life can also be decisive. CONCLUSION: We are still lacking a more detailed
understanding of the interaction between natural, environmental biodiversity, and
health, which calls for new innovative and more long-term investigations. The
outcomes should be utilized in policy and urban planning efforts, promoting human
interaction with natural biodiversity, and supporting a healthy lifestyle.
PMID- 27490123
TI - An update on ocular allergy.
AB - PURPOSE OF REVIEW: The update reviews prevalence, classification, cause, and
treatment options for allergic eye disease. RECENT FINDINGS: The incidence of
allergic eye disease is underreported but may affect almost all patients with
allergic rhinitis. Increased rates of oculonasal symptoms have been reported in
the United States resulting in significant economic expenditures. The spectrum of
allergic conjunctivitis and its differential considerations include seasonal and
perennial conjunctivitis, vernal and atopic keratoconjunctivitis, and giant
papillary conjunctivitis. Patients with allergic conjunctivitis have classic
immunoglobulin E-mediated pathophysiology and treatments directed at allergen
avoidance, traditional pharmacotherapy with oral antihistamines, topical dual
acting antihistamine/mast cell stabilizer agents, and treatment of tear film
dysfunction are first-line management strategies. Immunotherapy is an effective
treatment option and refractory cases may require ophthalmology comanagement for
consideration of topical ester-based corticosteroid therapy and consideration of
topical immunomodulators. SUMMARY: Ocular allergy involving specific modifiable
and treatable environmental sensitizations is common and often underrecognized.
It can impair quality of life to varying degrees. Some cases are quite refractory
to management and may require multidisciplinary coordination of care between
allergy and ophthalmology specialists. Understanding classification, triggers,
and treatment options is important in designing the most appropriate patient
tailored management plans.
PMID- 27490125
TI - The 'omics' revolution: redefining the understanding and treatment of allergic
skin diseases.
AB - PURPOSE OF REVIEW: To evaluate how the genomic, transcriptomic, and proteomic
profiles of allergic skin diseases, like atopic dermatitis and allergic contact
dermatitis, contribute to their understanding and promote their therapeutic
development. RECENT FINDINGS: The '-omics' revolution has facilitated the
quantification of inflammatory skin diseases at the molecular level, expanding
our understanding of disease pathogenesis. It has also greatly expanded once
limited treatment options and improved the ability to define posttreatment
improvements, beyond clinical scores. The findings on the genomic/transcriptomic
level are also complemented by proteomic data, contributing to the understanding
of the later changes taking place in the final stages of protein formation.
Atopic dermatitis is defined as a Th2/Th22 polarized disease with some
contributions of Th17 and Th1 pathways. In atopic dermatitis, studies of
biologics and small molecules, targeting specific pathways upregulated in atopic
dermatitis, seem to provide well tolerated alternatives to conventional
immunosuppressive therapies (i.e. corticosteroids and cyclosporine A),
particularly for severe patients. Allergic contact dermatitis is defined as
having Th1/Th17-centered inflammation, especially with nickel-induced disease,
but additional pathways, including Th2 and Th22, are upregulated with other
allergens (i.e. fragrance). SUMMARY: Supplementing studies of allergic skin
diseases with '-omics' approaches are transforming the pathogenic understanding,
diagnosis and, perhaps, also the treatment of these diseases.
PMID- 27490124
TI - Epidemiology of severe anaphylaxis: can we use population-based data to
understand anaphylaxis?
AB - PURPOSE OF REVIEW: The observed increase in incidence of allergic disease in many
regions over the past 3 decades has intensified interest in understanding the
epidemiology of severe allergic reactions. We discuss the issues in collecting
and interpreting these data and highlight current deficiencies in the current
methods of data gathering. RECENT FINDINGS: Anaphylaxis, as measured by hospital
admission rates, is not uncommon and has increased in the United Kingdom, the
United States, Canada, and Australia over the last 10-20 years. All large
datasets are hampered by a large proportion of uncoded, 'unspecified' causes of
anaphylaxis. Fatal anaphylaxis remains a rare event, but appears to be increasing
for medication in Australia, Canada, and the United States. The rate of fatal
food anaphylaxis is stable in the United Kingdom and the United States, but has
increased in Australia. The age distribution for fatal food anaphylaxis is
different to other causes, with data suggesting an age-related predisposition to
fatal outcomes in teenagers and adults to the fourth decade of life. SUMMARY: The
increasing rates of food and medication allergy (the latter exacerbated by an
ageing population) has significant implications for future fatality trends. An
improved ability to accurately gather and analyse population-level anaphylaxis
data in a harmonized fashion is required, so as to ultimately minimize risk and
improve management.
PMID- 27490126
TI - A systematic review of the role of interleukin-17 and the interleukin-20 family
in inflammatory allergic skin diseases.
AB - PURPOSE OF REVIEW: Allergic skin diseases include atopic dermatitis/eczema,
contact dermatitis, and drug hypersensitivity. Allergic skin diseases have a high
prevalence. Atopic dermatitis is one of the most common inflammatory skin
diseases and similar for allergic rhinitis and allergic asthma. Over a long
period, allergic diseases have been regarded as immunoglobulin E-mediated T
helper-2 (Th2)-driven. But new cytokines and T cells have been discovered within
the last years. In this systematic review, the focus is laid on interleukin-17
(IL-17) and the interleukin-20 (IL-20) family which appear to be fine-tuning the
Th2-driven answer. RECENT FINDINGS: IL-17 is a proinflammatory cytokine, which is
produced by T cells. Primarily, IL-17 is produced by activated CD4+ cells, called
Th-17 cells. IL-17 regulates keratinocyte expression of adhesion molecules and
chemokines. IL-17 is involved in the pathogenesis of inflammatory diseases as
psoriasis, arthritis, and inflammatory bowel diseases. In allergic diseases, the
involvement of the TH17/IL17-pathway has only been recently described. Regarding
the IL-20 family, IL-22 is the most interesting and the most studied cytokine in
terms of allergic inflammatory disorders. IL-22 is produced by T-helper 22 cells,
a new subset of CD4+ cells. SUMMARY: IL-17 as well as IL-22 seem to play a role
in the pathogenesis of allergic skin diseases.
PMID- 27490127
TI - Atopic dermatitis: new evidence on the role of allergic inflammation.
AB - PURPOSE OF REVIEW: Atopic dermatitis is a chronic relapsing inflammatory skin
disease. In the presence of a complex genetic background, there is increasing
evidence for the role of specific allergenic trigger factors in perpetuating skin
inflammation in sensitized atopic dermatitis patients. In this review, clinical
and in-vitro data so far published on allergen-induced adaptive immune responses
in atopic dermatitis are summarized. RECENT FINDINGS: Emerging new data have been
published particularly on adaptive immune responses to inhalant allergens in
atopic dermatitis. In a randomized controlled study, the induction of a flare-up
by grass pollen exposure in sensitized atopic dermatitis patients could be
demonstrated for the first time. T cells directed to the two major allergens of
house dust mite have been characterized to display a Th2, and moreover, a Th17
and Th2/Th17 phenotype in sensitized atopic dermatitis patients. With regard to
microbial antigens, T cell-mediated immune responses directed to proteins of the
species themselves can be observed - as has been published for Staphylococcus
aureus and Malassezia spp. Beyond this, specific T-cell activation to cross
reacting human proteins might further trigger the disease in distinct patients.
The role of 'autoallergic' phenomena in atopic dermatitis, because of human
antigens without known cross-reactivity to environmental allergens, is currently
under investigation as well. SUMMARY: Recent findings on immunological and
clinical characteristics of adaptive immune responses to allergens in atopic
dermatitis, but also on the identification of new, potentially relevant allergen
sources might contribute to the development of effective treatment strategies
'customized' for allergic inflammation in atopic dermatitis in future.
PMID- 27490128
TI - Leveraging Methylome-Environment Interaction to Detect Genetic Determinants of
Disease.
AB - OBJECTIVE: The association between DNA methylation and a trait of interest may
depend on an environmental exposure, and incorrectly accounting for this
dependence can lead to a reduction in power of the standard tests used in
epigenome-wide association studies. We present the M-ME test to jointly test for
the main effect of DNA methylation and methylation-environment interaction.
METHODS: Through simulation, we compare the power and type 1 error of the M-ME
test to a standard marginal test (M test) and a standard interaction test (ME
test) under 1,800 different underlying models. These models allow for methylation
environment correlation and measurement error in the exposure. RESULTS: In many
true underlying models, either the M test or the ME test has very low power, but
the M-ME test has optimal or nearly optimal power to detect a DNA methylation
effect in all models considered, including those with methylation- environment
dependence and measurement error in the exposure. Type 1 error inflation occurs
in the tests when the exposure is measured with error and correlated with DNA
methylation. CONCLUSION: The M-ME test is an attractive choice for studies aiming
to detect any DNA methylation association when little is known about the
epigenetic associations a priori.
PMID- 27490129
TI - Predictors of Ventriculoperitoneal Shunt Failure in Children Undergoing Initial
Placement or Revision.
AB - BACKGROUND: Ventriculoperitoneal (VP) shunt placement, the mainstay of treatment
for hydrocephalus, can place a substantial burden on patients and health care
systems because of high complication and revision rates. We aimed to identify
factors associated with 30-day VP shunt failure in children undergoing either
initial placement or revision. METHODS: VP shunt placements performed on patients
in the 2012-2013 American College of Surgeons National Surgical Quality
Improvement Program (NSQIP) Pediatric were identified. RESULTS: VP shunts were
placed in 3,984 patients either as an initial placement (n = 1,093) or as a
revision (n = 2,891). Compared to the initial-placement group, the revision group
was significantly more likely to experience shunt failure (14 vs. 8%, p <
0.0001). In the initial-placement group, congenital hydrocephalus was
independently associated with shunt failure (OR 1.83; 95% CI 1.01-3.31, p =
0.047). In the revision group, cardiac risk factors (OR 1.38; 95% CI 1.00-1.90, p
= 0.047), a chronic history of seizures (OR 1.33; 95% CI 1.04-1.71, p = 0.022),
and a history of neuromuscular disease (OR 0.61; 95% CI 0.41-0.90, p = 0.014)
were independently associated with shunt failure. CONCLUSIONS: Identifying the
factors associated with VP shunt failure may allow the development of
interventions to decrease failures. Further refinement of the collected variables
in the NSQIP Pediatric specific to neurosurgical procedures is necessary to
identify modifiable risk factors.
PMID- 27490130
TI - What Is the CT Dose Report Sheet and Why Is It Useful?
PMID- 27490131
TI - Diagnostic and Management Strategies for Multiligament Knee Injuries: A Critical
Analysis Review.
AB - Multiligament knee injuries have a strong association with periarticular soft
tissue and neurovascular injuries, which must not be overlooked in the initial
evaluation of the patient. Even though magnetic resonance imaging (MRI) is
imperative for a complete evaluation of the damaged ligamentous knee restraints,
stress radiography aids in establishing the functional consequence of the MRI
findings and may assist in directing reconstruction. Although cruciate ligament
tears are generally reconstructed, a combined repair-reconstruction approach is
most useful for collateral ligaments and extra-articular structures, with
incorporation of local tissue into the reconstruction whenever possible.
Regardless of the timing and operative technique chosen, patients with
multiligament knee injuries are at high risk for complications and long-term
disability.
PMID- 27490132
TI - Surgical and Functional Outcomes After Limb-Preservation Surgery for Tumor in
Pediatric Patients: A Systematic Review.
AB - BACKGROUND: Limb-salvage surgery and segmental reconstruction for the treatment
of lower extremity osseous tumors in the pediatric population have been described
in the literature, but there is little consensus regarding the optimal surgical
treatment for this patient population. METHODS: A systematic review of the
literature was performed to identify studies focusing on limb-salvage procedures
in pediatric patients who were managed with one of three reconstructions with use
of a metallic endoprosthesis, allograft, or allograft-prosthesis composite. Data
were segregated according to the excised and reconstructed anatomical location
(proximal part of the femur, total femur, distal part of the femur, proximal part
of the tibia) and were collated to assess modes of failure and functional
outcomes of each reconstruction type for each anatomic location. RESULTS: Sixty
articles met the inclusion criteria; all were Level-IV evidence, primarily
consisting of small, retrospective case series. Infection was a primary mode of
failure across all reconstruction types and locations, whereas allograft
reconstructions were susceptible to structural failure as well. The rate of
failure in the pediatric population correlated well with previously published
results for adults. The incidence of subsequent amputation was lower in the
pediatric population (5.2%) than has been reported in adults (9.5%) (p = 0.013).
Meaningful growth of expandable metallic endoprostheses was reported in the
literature, with an overall rate of leg-length discrepancy of 13.4% being noted
at the time of the latest follow-up. The Musculoskeletal Tumor Society (MSTS)
questionnaire was the most consistently used outcome measure in the literature,
with average scores ranging from 71.0% to 86.8%, depending on reconstruction type
and anatomic location. CONCLUSIONS: The current state of the literature detailing
the surgical and functional outcomes of segmental reconstruction for the
treatment of pediatric bone tumors is limited to Level-IV evidence and is
complicated by under-segregation of the data by age and anatomical location of
the reconstruction. Despite these limitations, pediatric limb-salvage surgery
demonstrates satisfactory initial surgical and functional outcomes. LEVEL OF
EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 27490133
TI - The Effect of Diabetes Mellitus on Total Joint Arthroplasty Outcomes.
AB - Diabetes has negative effects on the outcomes of total joint arthroplasty,
including increased numbers of complications, decreased function, early revision,
and higher costs. The prevalence of diabetes is increasing rapidly worldwide;
therefore, the orthopaedic surgeon should have an understanding of how diabetes
affects surgical outcomes.
PMID- 27490134
TI - Is There a Genetic Predisposition to Frozen Shoulder?: A Systematic Review and
Meta-Analysis.
AB - BACKGROUND: Frozen shoulder is a common disorder that leads to substantial
functional loss for patients by impairing activities of daily living. It also
adversely affects patients and society by impairing the ability to work. Its
pathogenesis is not fully understood. The aim of the present study was to perform
a systematic review and meta-analysis to assess the evidence suggesting a genetic
link to frozen shoulder. METHODS: A literature search of MEDLINE, EMBASE, and
CINAHL databases using relevant keywords revealed 5506 studies. After appropriate
screening of titles, abstracts, and full studies, seven studies were analyzed.
RESULTS: Three studies investigated rates of frozen shoulder among relatives. One
study (n = 1828 twin pairs) showed an 11.6% prevalence in twin pairs and
demonstrated a heritability of 42% for frozen shoulder after adjusting for age. A
second study (n = 273) showed that 20% of patients with frozen shoulder had a
positive family history involving a first-degree relative. The relative risk of
frozen shoulder was 4:1 when all patients with frozen shoulder were compared with
a control population. A third study (n = 87) showed that 29% of patients with
frozen shoulder had a first-degree relative with frozen shoulder. Two studies
evaluated racial predilection for frozen shoulder. One study (n = 50) reported a
substantially higher number of white patients (76%) with frozen shoulder than
black patients (24%). A second study (n = 87) showed that being born or having
parents or grandparents born in the British Isles were risk factors for frozen
shoulder. Four immunological studies investigated human leukocyte antigen (HLA)
B27 as a risk factor for frozen shoulder. Meta-analysis of two of these studies
with clearly defined controls showed significantly higher rates of HLA-B27
positivity in patients with frozen shoulder as compared with controls (p <
0.001). CONCLUSION: The limited evidence points toward a genetic link to frozen
shoulder. We used family history and racial predilection as markers for genetic
association, both of which indicated the presence of a genetic predisposition to
frozen shoulder. However, as there is a lack of unbiased genetic approaches,
there is an opportunity for genome-wide association studies to address
definitively the molecular genetics of frozen shoulder. Such studies may
eventually lead to a better understanding of the pathogenesis of frozen shoulder
and the development of novel therapeutic interventions. LEVEL OF EVIDENCE:
Prognostic Level IV. See Instructions for Authors for a complete description of
levels of evidence.
PMID- 27490135
TI - First-Principles Study of the Role of O2 and H2O in the Decoupling of Graphene on
Cu(111).
AB - The structural and electronic properties of graphene coated on a Cu(111) surface
can be strongly influenced by the arrangement of adsorbates at the graphene
edges. Oxygen and water intercalation at the graphene edges could lead to
oxidation and hydrolysis at the graphene/Cu(111) interface, eventually causing
decoupling of graphene from the Cu substrate. However, the reaction pathways for
oxygen or water (or both) intercalation at the graphene edges are not well
understood at the molecular level. Using ab initio density functional theory
calculations, we observed a strong hybridization of pi orbitals at a zigzag edge
of a graphene nanoribbon (GNR) on a bare Cu(111) surface, whereas such
hybridization was absent for the corresponding armchair edge under otherwise
identical conditions. These results indicate that the edge type influences the
oxidation chemistry beneath the GNR. Moreover, we demonstrate that the presence
of oxygen species, as well as GNR, facilitates the propagation of H2O. The
following decoupling mechanisms are discussed: (i) GNRs with armchair edge
configurations on Cu(111) can be decoupled via a sequential reaction that
involves O2 dissociation followed by H2O intercalation, whereas (ii) GNRs with
zigzag edge configurations on Cu(111) can be decoupled by oxygen intercalation.
PMID- 27490136
TI - Novel function of the endoplasmic reticulum degradation-enhancing alpha
mannosidase-like proteins in the human hepatitis B virus life cycle, mediated by
the middle envelope protein.
AB - Cells replicating the human hepatitis B virus (HBV) express high levels of
degradation-enhancing alpha-mannosidase-like proteins (EDEMs), a family of
proteins involved in the endoplasmic reticulum associated degradation, one of the
pathways activated during the unfolded protein response. Owing to their alpha-1,2
mannosidase activity, the EDEM1-3 proteins are able to process the N-linked
glycans of misfolded or incompletely folded proteins, providing the recognition
signal for their subsequent degradation. The HBV small (S), medium (M), and large
(L) surface proteins bear an N-linked glycosylation site in the common S domain
that is partially occupied in all proteins. The M protein contains an additional
site in its preS2 domain, which is always functional. Here, we report that these
oligosaccharides are processed by EDEMs, more efficiently by EDEM3, which induces
degradation of L and S proteins, accompanied by a reduction of subviral particles
production. In striking contrast, M not only is spared from degradation but its
trafficking is also accelerated leading to an improved secretion. This unusual
behavior of the M protein requires strictly the mannose trimming of the preS2 N
linked glycan. Furthermore, we show that HBV secretion is significantly inhibited
under strong endoplasmic reticulum stress conditions when M expression is
prevented by mutagenesis of the viral genome. These observations unfold unique
properties of the M protein in the HBV life cycle during unfolded protein
response and point to alternative mechanisms employed by EDEMs to alleviate this
stress in case of necessity by promoting glycoprotein trafficking rather than
degradation.
PMID- 27490137
TI - The Olympic Games and Athletic Sex Assignment.
PMID- 27490138
TI - Fat-Containing Hypermetabolic Masses on FDG PET/CT: A Spectrum of Benign and
Malignant Conditions.
AB - OBJECTIVE: This article focuses on identifying the imaging appearances of
hypermetabolic fatty masses and masslike lesions on PET/CT and understanding the
diagnostic challenges radiologists may face while interpreting findings of these
lesions on PET/CT. This article provides an approach to aid in the diagnosis of
these lesions and the appropriate management of patients. CONCLUSION: Both
malignant and benign fat-containing masses and masslike lesions can show
hypermetabolic activity on PET/CT. Although the differential diagnosis is broad,
clinical history, anatomic location, and knowledge of anatomic variants and
imaging features can help radiologists avoid misinterpretation of benign fatty
lesions as malignancy.
PMID- 27490139
TI - An Azulene-Containing Low Bandgap Small Molecule for Organic Photovoltaics with
High Open-Circuit Voltage.
AB - A simple azulene-containing squaraine dye (AzUSQ) showing bandgap of 1.38 eV and
hole mobility up to 1.25*10(-4) cm(2) V(-1) s(-1) was synthesized. With its
low bandgap, an organic photovoltaic (OPV) device based on it has been made that
exhibits an impressive open-circuit voltages (Voc ) of 0.80 V. Hence, azulene
might be a promising structural unit to construct OPV materials with simultaneous
low bandgap, high hole mobility and high Voc .
PMID- 27490140
TI - Revisiting the scissor-like mechanism of activation for the erythropoietin
receptor.
AB - An interpretation of alternative crystal structures of the erythropoietin
receptor, with and without ligand, led to the proposal of a scissor-like
mechanism of activation. This model has been propagated in the literature and is
still being used to interpret crystal structures of related type-I cytokine
receptors. Here, we assess whether the model remains compatible with current
knowledge on the family of type-I cytokine receptors, and consider whether the
model, as initially presented, is truly supported by the crystal structures on
which it was originally based.
PMID- 27490141
TI - Myosin myopathy with external ophthalmoplegia associated with a novel homozygous
mutation in MYH2.
PMID- 27490142
TI - Medial Patellofemoral Ligament Reconstruction.
PMID- 27490143
TI - Treatment of Glenoid Bone Deficiency in Total Shoulder Arthroplasty: A Critical
Analysis Review.
PMID- 27490144
TI - Osteochondritis Dissecans of the Knee.
PMID- 27490145
TI - Jones Fractures: Pathophysiology and Treatment.
PMID- 27490146
TI - Synthesis of Biaryl Ethers by the Copper-Catalyzed Chan-Evans-Lam Etherification
from Benzylic Amine Boronate Esters.
AB - The copper-catalyzed etherification of ortho-borylated benzylic amines with
phenols has been achieved to provide biaryl ethers that are prevalent in
biologically active compounds. A variety of substitution patterns on the aryl
boronate ester and the phenol are tolerated under the reaction conditions,
providing moderate to high yields. A competition reaction between phenol and
aniline revealed condition-dependent selectivity in which the phenol could be
highly favored over the aniline.
PMID- 27490148
TI - Deterministic Migration-Based Separation of White Blood Cells.
AB - Functional and phenotypic analyses of peripheral white blood cells provide useful
clinical information. However, separation of white blood cells from peripheral
blood requires a time-consuming, inconvenient process and thus analyses of
separated white blood cells are limited in clinical settings. To overcome this
limitation, a microfluidic separation platform is developed to enable
deterministic migration of white blood cells, directing the cells into designated
positions according to a ridge pattern. The platform uses slant ridge structures
on the channel top to induce the deterministic migration, which allows efficient
and high-throughput separation of white blood cells from unprocessed whole blood.
The extent of the deterministic migration under various rheological conditions is
explored, enabling highly efficient migration of white blood cells in whole blood
and achieving high-throughput separation of the cells (processing 1 mL of whole
blood less than 7 min). In the separated cell population, the composition of
lymphocyte subpopulations is well preserved, and T cells secrete cytokines
without any functional impairment. On the basis of the results, this microfluidic
platform is a promising tool for the rapid enrichment of white blood cells, and
it is useful for functional and phenotypic analyses of peripheral white blood
cells.
PMID- 27490147
TI - Inspiring change: humanities and social science insights into the experience and
management of breathlessness.
AB - PURPOSE OF REVIEW: Breathlessness can be debilitating for those with chronic
conditions, requiring continual management. Yet, the meaning of breathlessness
for those who live with it is poorly understood in respect of its subjective,
cultural, and experiential significance. This article discusses a number of
current issues in understanding the experience of breathlessness. RECENT
FINDINGS: Effective communication concerning the experience of breathlessness is
crucial for diagnosis, to identify appropriate treatment, and to provide patients
with the capacity to self-manage their condition. However, there is an evident
disconnect between the way breathlessness is understood between clinical and lay
perspectives, in terms of awareness of breathlessness, the way symptoms are
expressed, and acknowledgement of how it affects the daily lives of patients.
SUMMARY: The review highlights the need for integrated multidisciplinary work on
breathlessness, and suggests that effective understanding and management of
breathlessness considers its wider subjective and social significance.
PMID- 27490149
TI - Characterization of lower urinary tract symptoms in patients with idiopathic
normal pressure hydrocephalus.
AB - AIMS: The purpose of this study was to evaluate lower urinary tract symptoms
(LUTS) in idiopathic normal pressure hydrocephalus (iNPH). METHODS: Patients with
new-onset iNPH were prospectively evaluated for LUTS via detailed history and
physical, and administration of questionnaires from the International
Consultation on Incontinence to assess incontinence (ICIq-UI), overactive bladder
(ICIq-OAB), and quality of life (ICIq-LUTqol), as well as the American Urological
Association Symptom Score bother scale. All patients with moderate-to-severe LUTS
were offered urodynamic testing. Sub-analysis was performed based on gender,
medical comorbidities, and age. RESULTS: Fifty-five consecutive patients with
iNPH completed the initial evaluation and surveys. Total urinary incontinence
score was mild to moderate (8.71 +/- 0.64: 0-21 scale) with 90.9% experiencing
leakage and 74.5% reporting urge incontinence. The most common OAB symptom was
nocturia (2.2 +/- 0.14: 0-4 scale) with urge incontinence the most bothersome
(3.71 +/- 0.44: 0-10 scale). Quality-of-life impact was moderate (4.47 +/- 0.4: 0
10 scale) and American Urological Association Symptom Score bother scale was 2.89
+/- 0.22 (0-6 scale). Urodynamics testing revealed 100% detrusor overactivity and
mean bladder capacity of 200 mL. Several differences were identified based on
gender, medical comorbidities, and age. CONCLUSIONS: Patients with iNPH present
with mild-moderate incontinence of which nocturia is the most common symptom,
urge incontinence the most bothersome, with 100% of patients having detrusor
overactivity. Younger patients experienced greater bother related to LUTS. To our
knowledge, this is the only prospective evaluation of urinary symptoms in
patients with new-onset iNPH.
PMID- 27490150
TI - Assessment and Treatment of Malnutrition in Orthopaedic Surgery.
PMID- 27490151
TI - The Role of Evidence-Based Medicine in Clinical Practice Policy.
PMID- 27490152
TI - Achilles Tendinopathy.
PMID- 27490153
TI - Pathophysiology and Treatment of Spinal Tuberculosis.
PMID- 27490154
TI - Prevention of Anterior Cruciate Ligament Rupture in Female Athletes: A Systematic
Review.
AB - BACKGROUND: A number of reports have been published on the effectiveness and
design of intervention programs for the prevention of rupture of the anterior
cruciate ligament (ACL) in female athletes. The purpose of this study was to
systematically review the literature to determine the effectiveness of
neuromuscular training programs in preventing ACL injury in female athletes.
METHODS: A systematic review was performed with use of the PubMed, MEDLINE,
Embase, and Cochrane Central Register of Controlled Trials databases. The search
terms included "anterior cruciate ligament" and "ACL" combined with "prevention"
and "intervention." The searches included material indexed by September 30, 2013.
Data concerning study design, the characteristics of participants, the details of
the neuromuscular programs, the types of sports, and number of ACL ruptures were
extracted from the studies. Study heterogeneity was assessed with funnel plot and
Egger regression methods. Pooled effects were calculated with use of a
DerSimonian-Laird random-effects model. The number needed to treat was calculated
on the basis of pooled incidence data. RESULTS: The risk of ACL rupture was 1.83
times higher for female athletes who did not participate in neuromuscular ACL
prevention training programs (odds ratio [OR], 1.83; 95% confidence interval [95%
CI], 1.08 to 3.10; p = 0.02). In studies that focused exclusively on soccer, the
risk of ACL rupture was 2.62 times higher for nonparticipating athletes (OR,
2.62; 95% CI, 1.59 to 4.32; p < 0.01). When the data were analyzed according to
the timing of the intervention, no significant effects were found. In studies in
which the program took place both preseason and in-season, the risk (odds ratio)
of ACL rupture for nonparticipating athletes was 2.34 (95% CI, 0.82 to 6.7; p =
0.11). In studies in which the intervention took place in-season only, the risk
(odds ratio) of ACL rupture for nonparticipating athletes was 1.25 (95% CI, 0.23
to 6.75; p = 0.8). The number needed to treat to prevent a single ACL rupture was
128.7 athletes. We found no significant heterogeneity among the included studies.
The I value was 35.40% (p = 0.11). No significant publication bias was found in
our included studies. CONCLUSIONS: The results of this systematic review and meta
analysis favor a protective effect of neuromuscular training programs on the risk
of ACL rupture in female athletes. This protective effect is more pronounced in
soccer players. Additional research is needed to design the optimal training
program. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions to Authors for
a complete description of levels of evidence.
PMID- 27490155
TI - Smart Organic Two-Dimensional Materials Based on a Rational Combination of Non
covalent Interactions.
AB - Rational design of organic 2D (O2D) materials has made some progress, but it is
still in its infancy. A class of self-assembling small molecules is presented
that form nano/microscale supramolecular 2D materials in aqueous media. A
judicial combination of four different intermolecular interactions forms the
basis for the robust formation of these ultrathin assemblies. These assemblies
can be programmed to disassemble in response to a specific protein and release
its non-covalently bound guest molecules.
PMID- 27490156
TI - Rising trends in surgery for rotator cuff disease in Western Australia.
AB - BACKGROUND: Increasing rates of surgery for rotator cuff disease have been
reported in the past decade in a number of countries worldwide. Rising surgery
rates do not correspond with equivalent increases in shoulder pain prevalence.
The aims of the study were: to investigate trends in population-adjusted surgical
rates for rotator cuff disease in Western Australia (WA) from 2001 to 2013; to
compare population-adjusted arthroscopic surgical trends between (i) private
versus public hospital setting; (ii) sex and (iii) different age groups; and to
evaluate rising health care costs associated with arthroscopic surgical rates for
rotator cuff disease. METHODS: Numbers and costs for surgical procedures for
rotator cuff disease performed in WA were extracted from the WA Department of
Health database for the 13-year period, 2001-2013. RESULTS: Rising surgical
trends were demonstrated with arthroscopic subacromial decompression (ASAD) and
arthroscopic reconstruction showing large proportional increases of 108.7 and
68.4%, respectively. Increasing trends were mostly linear across private and
public hospital settings, gender groups and different age groups. The rise in
consumer price index-adjusted costs for ASAD in private and public hospitals was
273.7 and 320.8%, respectively, and for arthroscopic reconstruction 220.2 and
472.5%, respectively. CONCLUSION: The substantial increase in arthroscopic
surgery rates for rotator cuff disease and associated costs in WA over the period
2001-2013 is in spite of evidence that surgical outcomes are no different to
exercise interventions. Conservative treatments should be recommended as an
initial treatment choice, to arrest escalating health care costs.
PMID- 27490157
TI - Clostridial Gas Gangrene of the Abdominal Wall After Laparoscopic
Cholecystectomy: A Case Report and Review.
AB - Clostridial gas gangrene is a rare, yet severe, complication after laparoscopic
cholecystectomy. We present a case report of a 48-year-old man with obesity,
coronary artery disease, and diabetes, who developed clostridial gas gangrene of
the abdominal wall after an uncomplicated laparoscopic cholecystectomy. Although
the diagnosis was missed initially, successful radical surgical debridement was
performed and the patient survived. Pathogenesis, symptoms, prognostic factors,
and the best treatment are discussed.
PMID- 27490158
TI - Visualization of the airway in infants with MRI using pointwise encoding time
reduction with radial acquisition (PETRA).
AB - PURPOSE: To assess airway visibility in infants using pointwise encoding time
reduction with radial acquisition (PETRA). MATERIALS AND METHODS: PETRA was
obtained in 37 infants (gestational age: 23-43 weeks; postconceptional age: 34-46
weeks) using 3T magnetic resonance imaging (MRI) without respiratory gating. The
visibility of the branching point and the airway structures, including the
trachea and bronchi, on PETRA was scored by two experienced pediatric
radiologists using a four-point scale (0-3). The rates of good visibility (score
3 or 2) were calculated for each airway structure. Interrater agreement was
evaluated by intraclass correlation coefficient (ICC). RESULTS: For readers 1 and
2, good visibility was achieved for the branching point of the main bronchi (76%
and 95%, respectively), trachea (97% and 95%, respectively), right main bronchus
(92% and 92%, respectively), and left main bronchus (97% and 84%, respectively).
Lower rates of visibility were achieved for the lobar bronchi. There was
substantial agreement (ICC: 0.61-0.79) between the two readers for all the airway
structures, except for the branching point at the right upper/middle lobe
bronchi, for which there was moderate agreement (ICC: 0.56). CONCLUSION: PETRA
has the potential for good airway visibility in infants, particularly for the
trachea and main bronchi. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging
2017;45:839-844.
PMID- 27490159
TI - Solvent-Regulated Asymmetric Hydrogenation of Quinoline Derivatives in
Oligo(Ethylene Glycol)s through Host-Guest Interactions.
AB - The asymmetric hydrogenation of quinolines in oligo(ethylene glycol)s (OEGs) and
poly(ethylene glycol)s (PEGs) with chiral cationic ruthenium diamine complexes
has been investigated. Interestingly, in liquid PEGs or long-chain OEGs, the Ru
catalysts lost their reactivity. Upon the addition of a little MeOH, the
hydrogenation of quinoline was switched "ON". Evidence from mass spectrometry and
control experiments revealed that encapsulation of the quinolinium salt by PEG or
long-chain OEG molecules through supramolecular interactions is possibly the main
reason for such a switchable hydrogenation reaction. Moreover, the asymmetric
hydrogenation of 2-substituted quinoline derivatives was achieved in triethylene
glycol (3-OEG), thereby affording 1,2,3,4-tetrahydroquinolines with excellent
reactivities and enantioselectivities (up to 99 % ee). Furthermore, the Ru
catalyst could be readily recycled for both pure 3-OEG and biphasic 3-OEG/n
hexane systems without a clear loss of reactivity and enantioselectivity.
PMID- 27490160
TI - From the Patient Perspective, Consent Forms Fall Short of Providing Information
to Guide Decision Making.
AB - OBJECTIVE: This study aimed to gather qualitative feedback on patient perceptions
of informed consent forms and elicit recommendations to improve readability and
utility for enhanced patient safety and engagement in shared decision making.
METHODS: Sixty interviews in personal interviews were conducted consisting of a
literacy and numeracy assessment, a comprehension quiz to assess retention of key
information, and open-ended questions to determine reactions, clarity of
information, and suggestions for improvement. RESULTS: Although 68% of the
participants had education beyond high school, many still missed comprehension
questions and found the forms difficult to read. Recurrent suggestions included
specific formatting changes to enhance readability, a need for additional sources
of information, mixed attitudes toward inclusion of risk information, and the
recognized importance of physician-patient conversations. CONCLUSIONS: This study
provides evidence from the patient perspective that consent forms are too complex
and fail to achieve comprehension. Future studies should be conducted using
patients' suggestions for form redesign and inclusion of supplemental educational
tools to optimize communication and safety to achieve more informed health care
decision making.
PMID- 27490161
TI - Nickel Nanofoam/Different Phases of Ordered Mesoporous Carbon Composite
Electrodes for Superior Capacitive Energy Storage.
AB - Electrochemical energy storage devices based on electric double layer capacitors
(EDLCs) have received considerable attention due to their high power density and
potential for obtaining improved energy density in comparison to the lithium ion
battery. Ordered mesoporous carbon (OMC) is a promising candidate for use as an
EDLC electrode because it has a high specific surface area (SSA), providing a
wider charge storage space and size-controllable mesopore structure with a long
range order, suppling high accessibility to the electrolyte ions. However, OMCs
fabricated using conventional methods have several drawbacks including low
electronic conductivity and long ionic diffusion paths in mesopores. We used
nickel nanofoam, which has a relatively small pore (sub-100 nm to subMUm) network
structure, as a current collector. This provides a significantly shortened
electronic/ionic current paths and plentiful surface area, enabling stable and
close attachment of OMCs without the use of binders. Thus, we present
hierarchical binder-free electrode structures based on OMC/Ni nanofoams. These
structures give rise to enhanced specific capacitance and a superior rate
capability. We also investigated the mesopore structural effect of OMCs on
electrolyte transport by comparing the capacitive performances of collapsed
lamellar, cylindrical, and spherical mesopore electrodes. The highly ordered and
straightly aligned cylindrical OMCs exhibited the highest specific capacitance
and the best rate capability.
PMID- 27490162
TI - TIOtropium Safety and Performance In Respimat(r) (TIOSPIRTM ): Analysis of Asian
cohort of COPD patients.
AB - BACKGROUND AND OBJECTIVE: The TIOtropium Safety and Performance In Respimat
(TIOSPIR) trial showed similar safety and exacerbation efficacy profiles for
tiotropium Respimat and HandiHaler in patients with COPD. The TIOSPIR results for
patients in Asia are presented here. METHODS: TIOSPIR evaluated once-daily
tiotropium Respimat 5 and 2.5 ug with HandiHaler 18 ug in patients with COPD.
Primary endpoints included time to death and time to first COPD exacerbation.
Safety and exacerbation efficacy profiles were determined for the Asian region,
and for Asia (all treatment arms pooled) versus the rest of the world (RoW).
RESULTS: In Asia (n = 2356), time to death was similar for Respimat 5 and 2.5 ug
versus HandiHaler 18 ug (hazard ratio (HR) (95% CI): 0.96 (0.67, 1.38) and 1.23
(0.87, 1.73)). Risk of COPD exacerbation was similar for Respimat 5 ug, but
increased for 2.5 ug versus HandiHaler 18 ug (HR (95% CI): 0.99 (0.85, 1.15) and
1.17 (1.00, 1.35)). Time to death in Asia and RoW was similar (HR (95% CI): 1.15
(0.99, 1.35)). Time to first COPD exacerbation was longer (HR (95% CI): 0.84
(0.78, 0.89)) and exacerbation rates were lower in Asia, but severe exacerbations
were more frequent than in the RoW. Risk of major adverse cardiovascular events
was similar for both regions. CONCLUSION: Similar safety and exacerbation
efficacy profiles were observed for tiotropium Respimat 5 ug and HandiHaler 18 ug
in patients with COPD from Asia, analogous to the global analysis. Asian patients
had lower risk of, and fewer exacerbations overall, but a higher proportion of
severe exacerbations than in the RoW.
PMID- 27490163
TI - Jabuticaba (Myrciaria cauliflora) Seeds: Chemical Characterization and Extraction
of Antioxidant and Antimicrobial Compounds.
AB - This study was aimed to assess the effect of time and temperature on the
extraction of antioxidant compounds from jabuticaba seeds (Myrciaria cauliflora
cv. Sabara), to optimize the solvent proportion (water, ethyl alcohol, and
propanone), and to characterize the extract according to the chemical
composition, antioxidant, and antimicrobial properties. Proximal composition,
total phenolic content (TPC), antioxidant, and antimicrobial activities were
analyzed. The optimized solvent ratio of 60% water and 40% propanone provided a
mean TPC of 8.65 g GAE/100 g seeds and the antioxidant activity toward 2,2
diphenyl-1-picrylhydrazyl (DPPH) was 82.79% +/- 0.50%. Time and temperature
parameters did not influence the yield of TPC. The gross seed extract was
partially purified and both exhibited a high antioxidant activity and
antimicrobial potential toward Gram-positive and Gram-negative bacteria. The
purified jabuticaba seed lyophilized extract contained a higher (P < 0.05) TPC, o
diphenols, flavonols, and antioxidant activity measured by the DPPH assay and
total reducing capacity as compared to the gross lyophilized extract.
Electrospray ionization coupled with tandem mass spectrometry (ESI-MS/MS) data
showed the presence of ellagitannins and ellagic acid in the extracts, which are
probably the responsible for the antimicrobial and antioxidant activities.
PMID- 27490164
TI - The Use of "Literary Fiction" to Promote Mentalizing Ability.
AB - Empathy is a multidimensional process that incorporates both mentalizing and
emotional sharing dimensions. Empathic competencies are important for creating
interpersonal relationships with other people and developing adequate social
behaviour. The lack of these social components also leads to isolation and
exclusion in healthy populations. However, few studies have investigated how to
improve these social skills. In a recent study, Kidd and Castano (2013) found
that reading literary fiction increases mentalizing ability and may change how
people think about other people's emotions and mental states. The aim of our
study was to evaluate the effects of reading literary fiction, compared to
nonfiction and science fiction, on empathic abilities. Compared to previous
studies, we used a larger variety of empathy measures and utilized a pre and post
test design. In all, 214 healthy participants were randomly assigned to read a
book representative of one of three literary genres (literary fiction,
nonfiction, science fiction). Participants were assessed before and after the
reading phase using mentalizing and emotional sharing tests, according to Zaki
and Ochsner' s (2012) model. Comparisons of sociodemographic, mentalizing, and
emotional sharing variables across conditions were conducted using ANOVA. Our
results showed that after the reading phase, the literary fiction group showed
improvement in mentalizing abilities, but there was no discernible effect on
emotional sharing abilities. Our study showed that the reading processes can
promote mentalizing abilities. These results may set important goals for future
low-cost rehabilitation protocols for several disorders in which the mentalizing
deficit is considered central to the disease, such as Autism Spectrum Disorders
and Schizophrenia.
PMID- 27490165
TI - CS-MINER: A Tool for Association Mining in Binding-Database.
AB - This paper introduces the algorithms, implementation strategies, features, and
applications of CS-MINER, a tool for visualization and analysis of drug-like
chemical space. The CS-MINER is the abstract abbreviation for Chemical Space
Miner and correlates the medicinal target space and chemical space, in a
systematic way. The database in this software consists of a large collection of
drug-like molecules. To prepare this database, a large number of molecules for
110 important biological targets were collected from Binding-DB. A total of 1497
physicochemical properties were calculated for each molecule. The CS-MINER uses
the discriminant analysis techniques for tracing the collected data and finally
separates the molecules based on their therapeutic targets and activities. The
developed multivariate classifiers can be used for ligand-based virtual screening
of more than 0.5 million random molecules of PubChem and ZINC databases. In order
to validate the models, selected subspaces in CS-MINER were compared with
DrugBank molecules. At the end of the analysis, the software provides an
interactive environment for visualization of the selected chemical subspaces in
the form of 2- and 3-dimensional plots. In general, CS-MINER is a tool for
comparing the relative position of active biosimilar molecules in chemical space
and is freely available at www.csminer.com.
PMID- 27490166
TI - Discrete Biogeography Based Optimization for Feature Selection in Molecular
Signatures.
AB - Biomarker discovery from high-dimensional data is a complex task in the
development of efficient cancer diagnoses and classification. However, these data
are usually redundant and noisy, and only a subset of them present distinct
profiles for different classes of samples. Thus, selecting high discriminative
genes from gene expression data has become increasingly interesting in the field
of bioinformatics. In this paper, a discrete biogeography based optimization is
proposed to select the good subset of informative gene relevant to the
classification. In the proposed algorithm, firstly, the fisher-markov selector is
used to choose fixed number of gene data. Secondly, to make biogeography based
optimization suitable for the feature selection problem; discrete migration model
and discrete mutation model are proposed to balance the exploration and
exploitation ability. Then, discrete biogeography based optimization, as we
called DBBO, is proposed by integrating discrete migration model and discrete
mutation model. Finally, the DBBO method is used for feature selection, and three
classifiers are used as the classifier with the 10 fold cross-validation method.
In order to show the effective and efficiency of the algorithm, the proposed
algorithm is tested on four breast cancer dataset benchmarks. Comparison with
genetic algorithm, particle swarm optimization, differential evolution algorithm
and hybrid biogeography based optimization, experimental results demonstrate that
the proposed method is better or at least comparable with previous method from
literature when considering the quality of the solutions obtained.
PMID- 27490167
TI - Enhancing the Reliability of GPCR Models by Accounting for Flexibility of Their
Pro-Containing Helices: the Case of the Human mAChR1 Receptor.
AB - To better investigate the GPCR structures, we have recently proposed to explore
their flexibility by simulating the bending of their Pro-containing TM helices so
generating a set of models (the so-called chimeras) which exhaustively combine
the two conformations (bent and straight) of these helices. The primary objective
of the study is to investigate whether such an approach can be exploited to
enhance the reliability of the GPCR models generated by distant templates. The
study was focused on the human mAChR1 receptor for which a presumably reliable
model was generated using the congener mAChR3 as the template along with a second
less reliable model based on the distant beta2-AR template. The second model was
then utilized to produce the chimeras by combining the conformations of its Pro
containing helices (i.e., TM4, TM5, TM6 and TM7 with 16 modeled chimeras). The
reliability of such chimeras was assessed by virtual screening campaigns as
evaluated using a novel skewness metric where they surpassed the predictive power
of the more reliable mAChR1 model. Finally, the virtual screening campaigns
emphasize the opportunity of synergistically combining the scores of more
chimeras using a specially developed tool which generates highly predictive
consensus functions by maximizing the corresponding enrichment factors.
PMID- 27490168
TI - In Silico Estimation of Chemical Carcinogenicity with Binary and Ternary
Classification Methods.
AB - Carcinogenicity is one of the most concerned properties of chemicals to human
health, thus it is important to identify chemical carcinogenicity as early as
possible. In this study, 829 diverse compounds with rat carcinogenicity were
collected from Carcinogenic Potency Database (CPDB). Using six types of
fingerprints to represent the molecules, 30 binary and ternary classification
models were generated to predict chemical carcinogenicity by five machine
learning methods. The models were evaluated by an external validation set
containing 87 chemicals from ISSCAN database. The best binary model was developed
by MACCS keys and kNN algorithm with predictive accuracy at 83.91 %, while the
best ternary model was also generated by MACCS keys and kNN algorithm with
overall accuracy at 80.46 %. Furthermore, the best binary and ternary
classification models were used to estimate carcinogenicity of tobacco smoke
components containing 2251 compounds. 981 ones were predicted as carcinogens by
binary classification model, while 110 compounds were predicted as strong
carcinogens and 807 ones as weak carcinogens by ternary classification model. The
results indicated that our models would be helpful for prediction of chemical
carcinogenicity.
PMID- 27490169
TI - Novel Uses of In Vitro Data to Develop Quantitative Biological Activity
Relationship Models for in Vivo Carcinogenicity Prediction.
AB - The availability of large in vitro datasets enables better insight into the mode
of action of chemicals and better identification of potential mechanism(s) of
toxicity. Several studies have shown that not all in vitro assays can contribute
as equal predictors of in vivo carcinogenicity for development of hybrid
Quantitative Structure Activity Relationship (QSAR) models. We propose two novel
approaches for the use of mechanistically relevant in vitro assay data in the
identification of relevant biological descriptors and development of Quantitative
Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We
demonstrate that in vitro assay data can be used to develop QBAR models for in
vivo carcinogenicity prediction via two case studies corroborated with firm
scientific rationale. The case studies demonstrate the similarities between QBAR
and QSAR modeling in: (i) the selection of relevant descriptors to be used in the
machine learning algorithm, and (ii) the development of a computational model
that maps chemical or biological descriptors to a toxic endpoint. The results of
both the case studies show: (i) improved accuracy and sensitivity which is
especially desirable under regulatory requirements, and (ii) overall adherence
with the OECD/REACH guidelines. Such mechanism based models can be used along
with QSAR models for prediction of mechanistically complex toxic endpoints.
PMID- 27490170
TI - Multi-Component Protein - Protein Docking Based Protocol with External Scoring
for Modeling Dimers of G Protein-Coupled Receptors.
AB - In order to apply structure-based drug design techniques to GPCR complexes, it is
essential to model their 3D structure. For this purpose, a multi-component
protocol was derived based on protein-protein docking which generates populations
of dimers compatible with membrane integration, considering all reasonable
interfaces. At the next stage, we applied a scoring procedure based on up to
eleven different parameters including shape or electrostatics complementarity.
Two methods of consensus scoring were performed: (i) average scores of 100 best
scored dimers with respect to each interface, and (ii) frequencies of interfaces
among 100 best scored dimers. In general, our multi-component protocol gives
correct indications for dimer interfaces that have been observed in X-ray crystal
structures of GPCR dimers (opsin dimer, chemokine CXCR4 and CCR5 dimers, kappa
opioid receptor dimer, beta1 adrenergic receptor dimer and smoothened receptor
dimer) but also suggests alternative dimerization interfaces. Interestingly, at
times these alternative interfaces are scored higher than the experimentally
observed ones suggesting them to be also relevant in the life cycle of studied
GPCR dimers. Further results indicate that GPCR dimer and higher-order oligomer
formation may involve transmembrane helices (TMs) TM1-TM2-TM7, TM3-TM4-TM5 or TM4
TM5-TM6 but not TM1-TM2-TM3 or TM2-TM3-TM4 which is in general agreement with
available experimental and computational data.
PMID- 27490171
TI - On the Use of a Protic Ionic Liquid with a Novel Cation To Study Anion Basicity.
AB - The need for reliable means of ordering and quantifying the Lewis basicity of
anions is discussed and the currently available methods are reviewed. Concluding
that there is need for a simple impurity-insensitive tool, we have sought, and
here describe, a new method using NMR spectroscopy of a weak base, a substituted
urea, 1,3-dimethyl-2-imidazolidinone (DMI), as it is protonated by Bronsted acids
of different strengths and characters. In all cases studied the product of
protonation is a liquid (hence a protic ionic liquid). NMR spectroscopy detects
changes in the electronic structure of the base upon interaction with the proton
donors. As the proton-donating ability, that is, acidity, increases, there is a
smooth but distinct transition from a hydrogen-bonded system (with no net proton
transfer) to full ionicity. The liquid state of the samples and high
concentration of nitrogen atoms, despite the very low natural abundance of its
preferred NMR-active isotope ((15) N), make possible the acquisition of (15) N
spectra in a relatively short time. These (15) N, along with (13) C, chemical
shifts of the carbonyl atom, and their relative responses to protonation of the
carbonyl oxygen, can be used as a means, sensitive to anion basicity and
relatively insensitive to impurities, to sort anions in order of increasing
hydrogen bond basicity. The order is found to be as follows: SbF6 (-) ClO4 (-) >FSO3 (-) C (p.V175L) alteration in the proband. CONCLUSION: Overall, DES
established a likely molecular genetic diagnosis for a post-mortem case after
traditional testing methods were uninformative. The DES results allowed for
reproductive options, such as preimplantation genetic diagnosis (PGD) and/or
prenatal diagnosis, to be available to the parents in future pregnancies.
PMID- 27490175
TI - Analytical Model for Estimating the Zenith Angle Dependence of Terrestrial Cosmic
Ray Fluxes.
AB - A new model called "PHITS-based Analytical Radiation Model in the Atmosphere
(PARMA) version 4.0" was developed to facilitate instantaneous estimation of not
only omnidirectional but also angular differential energy spectra of cosmic ray
fluxes anywhere in Earth's atmosphere at nearly any given time. It consists of
its previous version, PARMA3.0, for calculating the omnidirectional fluxes and
several mathematical functions proposed in this study for expressing their zenith
angle dependences. The numerical values of the parameters used in these functions
were fitted to reproduce the results of the extensive air shower simulation
performed by Particle and Heavy Ion Transport code System (PHITS). The angular
distributions of ground-level muons at large zenith angles were specially
determined by introducing an optional function developed on the basis of
experimental data. The accuracy of PARMA4.0 was closely verified using multiple
sets of experimental data obtained under various global conditions. This
extension enlarges the model's applicability to more areas of research, including
design of cosmic-ray detectors, muon radiography, soil moisture monitoring, and
cosmic-ray shielding calculation. PARMA4.0 is available freely and is easy to
use, as implemented in the open-access EXcel-based Program for Calculating
Atmospheric Cosmic-ray Spectrum (EXPACS).
PMID- 27490176
TI - Synthetic Site-Selectively Mono-6-O-Sulfated Heparan Sulfate Dodecasaccharide
Shows Anti-Angiogenic Properties In Vitro and Sensitizes Tumors to Cisplatin In
Vivo.
AB - Heparan sulphate (HS), a ubiquitously expressed glycosaminoglycan (GAG),
regulates multiple cellular functions by mediating interactions between numerous
growth factors and their cell surface cognate receptors. However, the structural
specificity of HS in these interactions remains largely undefined. Here, we used
completely synthetic, structurally defined, alternating N-sulfated glucosamine
(NS) and 2-O-sulfated iduronate (IS) residues to generate dodecasaccharides
([NSIS]6) that contained no, one or six glucosamine 6-O-sulfates (6S). The aim
was to address how 6S contributes to the potential of defined HS
dodecasaccharides to inhibit the angiogenic growth factors FGF2 and VEGF165, in
vitro and in vivo. We show that the addition of a single 6S at the non-reducing
end of [NSIS]6, i.e. [NSIS6S]-[NSIS]5, significantly augments the inhibition of
FGF2-dependent endothelial cell proliferation, migration and sprouting in vitro
when compared to the non-6S variant. In contrast, the fully 6-O-sulfated
dodecasaccharide, [NSIS6S]6, is not a potent inhibitor of FGF2. Addition of a
single 6S did not significantly improve inhibitory properties of [NSIS]6 when
tested against VEGF165-dependent endothelial cell functions.In vivo, [NSIS6S]
[NSIS]5 blocked FGF2-dependent blood vessel formation without affecting tumor
growth. Reduction of non-FGF2-dependent ovarian tumor growth occurred when
[NSIS6S]-[NSIS]5 was combined with cisplatin. The degree of inhibition by
[NSIS6S]-[NSIS]5 in combination with cisplatin in vivo equated with that induced
by bevacizumab and sunitinib when administered with cisplatin. Evaluation of post
treatment vasculature revealed that [NSIS6S]-[NSIS]5 treatment had the greatest
impact on tumor blood vessel size and lumen formation. Our data for the first
time demonstrate that synthetic, structurally defined oligosaccharides have
potential to be developed as active anti-angiogenic agents that sensitize tumors
to chemotherapeutic agents.
PMID- 27490178
TI - Alkali Niobate and Tantalate Perovskites as Alternative Photocatalysts.
AB - Alkali tantalates and niobates are listed as important photocatalysts for the
development of renewable energy technologies and environmental remediation.
Herein, the photocatalytic degradation of methylene blue dye in aqueous solution
by using highly crystalline particles with perovskite-like structures, LiTaO3 ,
LiNbO3 , NaTaO3 , NaNbO3 , KNbO3 , and KTaO3 , is investigated. It is
demonstrated that ferroelectric KNbO3 is the most efficient photocatalyst of
those tested because it combines an electronic band structure that can respond
successfully to UVA light with a relatively high surface energy that enhances the
catalytic properties. Additionally, the built-in electric field due to internal
polarization of ferroelectric particles may contribute to the unique properties
of this functional photocatalyst. This work provides an ideal platform for the
rational design of more efficient ferroelectric-based photocatalytic devices.
PMID- 27490177
TI - Human Serum-Specific Activation of Alternative Sigma Factors, the Stress
Responders in Aggregatibacter actinomycetemcomitans.
AB - Aggregatibacter actinomycetemcomitans, a known pathogen causing periodontal
disease and infective endocarditis, is a survivor in the periodontal pocket and
blood stream; both environments contain serum as a nutrient source. To screen for
unknown virulence factors associated with this microorganism, A.
actinomycetemcomitans was grown in serum-based media to simulate its in vivo
environment. Different strains of A. actinomycetemcomitans showed distinct growth
phenotypes only in the presence of human serum, and they were grouped into high-
and low-responder groups. High-responders comprised mainly serotype c strains,
and showed an unusual growth phenomenon, featuring a second, rapid increase in
turbidity after 9-h incubation that reached a final optical density 2- to 7-fold
higher than low-responders. Upon further investigation, the second increase in
turbidity was not caused by cell multiplication, but by cell death. Whole
transcriptomic analysis via RNA-seq identified 35 genes that were up-regulated by
human serum, but not horse serum, in high-responders but not in low-responders,
including prominently an alternative sigma factor rpoE (sigmaE). A lacZ reporter
construct driven by the 132-bp rpoE promoter sequence of A. actinomycetemcomitans
responded dramatically to human serum within 90 min of incubation only when the
construct was carried by a high responder strain. The rpoE promoter is 100%
identical among high- and low-responder strains. Proteomic investigation showed
potential interactions between human serum protein, e.g. apolipoprotein A1
(ApoA1) and A. actinomycetemcomitans. The data clearly indicated a different
activation process for rpoE in high- versus low-responder strains. This
differential human serum-specific activation of rpoE, a putative extra
cytoplasmic stress responder and global regulator, suggests distinct in vivo
adaptations among different strains of A. actinomycetemcomitans.
PMID- 27490180
TI - Direct vs. Microclimate-Driven Effects of Tree Species Diversity on Litter
Decomposition in Young Subtropical Forest Stands.
AB - Effects of tree species diversity on decomposition can operate via a multitude of
mechanism, including alterations of microclimate by the forest canopy. Studying
such effects in natural settings is complicated by the fact that topography also
affects microclimate and thus decomposition, so that effects of diversity are
more difficult to isolate. Here, we quantified decomposition rates of standard
litter in young subtropical forest stands, separating effects of canopy tree
species richness and topography, and quantifying their direct and micro-climate
mediated components. Our litterbag study was carried out at two experimental
sites of a biodiversity-ecosystem functioning field experiment in south-east
China (BEF-China). The field sites display strong topographical heterogeneity and
were planted with tree communities ranging from monocultures to mixtures of 24
native subtropical tree species. Litter bags filled with senescent leaves of
three native tree species were placed from Nov. 2011 to Oct. 2012 on 134 plots
along the tree species diversity gradient. Topographic features were measured for
all and microclimate in a subset of plots. Stand species richness, topography and
microclimate explained important fractions of the variations in litter
decomposition rates, with diversity and topographic effects in part mediated by
microclimatic changes. Tree stands were 2-3 years old, but nevertheless tree
species diversity explained more variation (54.3%) in decomposition than
topography (7.7%). Tree species richness slowed litter decomposition, an effect
that slightly depended on litter species identity. A large part of the variance
in decomposition was explained by tree species composition, with the presence of
three tree species playing a significant role. Microclimate explained 31.4% of
the variance in decomposition, and was related to lower soil moisture. Within
this microclimate effect, species diversity (without composition) explained 8.9%
and topography 34.4% of variance. Topography mainly affected diurnal temperature
amplitudes by varying incident solar radiation.
PMID- 27490179
TI - Loss of Gravitropism in Farnesene-Treated Arabidopsis Is Due to Microtubule
Malformations Related to Hormonal and ROS Unbalance.
AB - Mode of action of farnesene, a volatile sesquiterpene commonly found in the
essential oils of several plants, was deeply studied on the model species
Arabidopsis thaliana. The effects of farnesene on the Arabidopsis root morphology
were evaluated by different microscopic techniques. As well, microtubules
immunolabeling, phytohormone measurements and ROS staining helped us to elucidate
the single or multi-modes of action of this sesquiterpene on plant metabolism.
Farnesene-treated roots showed a strong growth inhibition and marked
modifications on morphology, important tissue alterations, cellular damages and
anisotropic growth. Left-handed growth of farnesene-treated roots, reverted by
taxol (a known microtubule stabilizer), was related to microtubule condensation
and disorganization. As well, the inhibition of primary root growth, lateral root
number, lateral root length, and both root hairs length and density could be
explained by the strong increment in ethylene production and auxin content
detected in farnesene-treated seedlings. Microtubule alteration and hormonal
unbalance appear as important components in the mode of action of farnesene and
confirm the strong phytotoxic potential of this sesquiterpene.
PMID- 27490181
TI - Time-to-Detection of Inducible Macrolide Resistance in Mycobacterium abscessus
Subspecies and Its Association with the Erm(41) Sequevar.
AB - Mutations in the erm(41) gene of M.abscessus group organisms are associated with
differences in inducible macrolide resistance, with current recommendations being
to hold rapidly growing isolates for up to 14 days in order to ensure that
resistance which develops more slowly can be detected. This study aimed to
determine the ideal incubation time for accurate identification of inducible
macrolide resistance as well as to determine if there was an association between
the time taken to detect inducible resistance in M.abscessus group organisms and
their erm(41) sequevar. We amplified and sequenced the erm(41) genes of a total
of 104 M.abscessus group isolates and determined their sequevars. The isolates
were tested for phenotypic clarithromycin resistance at days 7, 10, 14 and 21,
using Trek Diagnostics Sensititre RAPMYCO microbroth dilution plates.
Associations between erm(41) gene sequevars and time to detection of resistance
were evaluated using Fisher's exact test in R. The samples included in this study
fell into 14 sequevars, with the majority of samples falling into Sequevar02
(16), Sequevar06 (15), Sequevar08 (7) and Sequvar 15 (31), and several isolates
that were in small clusters, or unique. The majority (82.7%) of samples
exhibiting inducible macrolide resistance were interpreted as resistant by day 7.
Two isolates in Sequevar02, which has a T28C mutation that is associated with
sensitivity, showed intermediate resistance at day 14, though the majority (13)
were sensitive at day 14. The majority of isolates with inducible macrolide
resistance fell into Sequevars 06,08 and 15, none of which contain the T28C
mutation. These sequevars were analyzed to determine if there was any correlation
between sequevar and time to detection of resistance. None was found. Based on
these findings, we recommend the addition of a day 7 read to the CLSI guidelines
to improve turn-around-times for these isolates. It is also recommended that
erm(41) gene sequencing be added to routine phenotypic testing for the resolution
of cases with difficult-to-interpret phenotypic results.
PMID- 27490182
TI - Using Cellular Communication Networks To Detect Air Pollution.
AB - Accurate real time monitoring of atmospheric conditions at ground level is vital
for hazard warning, meteorological forecasting, and various environmental
applications required for public health and safety. However, conventional
monitoring facilities are costly and often insufficient, for example, since they
are not representative of the larger space and are not deployed densely enough in
the field. There have been numerous scientific works showing the ability of
commercial microwave links that comprise the data transmission infrastructure in
cellular communication networks to monitor hydrometeors as a potential
complementary solution. However, despite the large volume of research carried out
in this emerging field during the past decade, no study has shown the ability of
the system to provide critical information regarding air quality. Here we reveal
the potential for identifying atmospheric conditions prone to air pollution by
detecting temperature inversions that trap pollutants at ground level. The
technique is based on utilizing standard signal measurements from an existing
cellular network during routine operation.
PMID- 27490183
TI - Correction: DNA-catalyzed glycosylation using aryl glycoside donors.
AB - Correction for 'DNA-catalyzed glycosylation using aryl glycoside donors' by
Anthony R. Hesser et al., Chem. Commun., 2016, 52, 9259-9262.
PMID- 27490184
TI - Corannulene-Helicene Hybrids: Chiral pi-Systems Comprising Both Bowl and Helical
Motifs.
AB - Two distinct structural elements that render pi-systems nonplanar, i.e., geodesic
curvature and helical motifs, have been combined into new polyarenes that contain
both features. The resultant corannulene-[n]helicenes (n = 5, 6) show unique
molecular dynamics in their enantiomerization processes, including inversion
motions of both the bowl and the helix. Optical resolution of a corannulene-based
skeletally chiral molecule was also achieved for the first time, and the
influence of the bowl-motif annulation on the chiroptical properties was
investigated.
PMID- 27490185
TI - Des-Acyl Ghrelin and Ghrelin O-Acyltransferase Regulate Hypothalamic-Pituitary
Adrenal Axis Activation and Anxiety in Response to Acute Stress.
AB - Ghrelin exists in two forms in circulation, acyl ghrelin and des-acyl ghrelin,
both of which have distinct and fundamental roles in a variety of physiological
functions. Despite this fact, a large proportion of papers simply measure and
refer to plasma ghrelin without specifying the acylation status. It is therefore
critical to assess and state the acylation status of plasma ghrelin in all
studies. In this study we tested the effect of des-acyl ghrelin administration on
the hypothalamic-pituitary-adrenal axis and on anxiety-like behavior of mice
lacking endogenous ghrelin and in ghrelin-O-acyltransferase (GOAT) knockout (KO)
mice that have no endogenous acyl ghrelin and high endogenous des-acyl ghrelin.
Our results show des-acyl ghrelin produces an anxiogenic effect under nonstressed
conditions, but this switches to an anxiolytic effect under stress. Des-acyl
ghrelin influences plasma corticosterone under both nonstressed and stressed
conditions, although c-fos activation in the paraventricular nucleus of the
hypothalamus is not different. By contrast, GOAT KO are anxious under both
nonstressed and stressed conditions, although this is not due to corticosterone
release from the adrenals but rather from impaired feedback actions in the
paraventricular nucleus of the hypothalamus, as assessed by c-fos activation.
These results reveal des-acyl ghrelin treatment and GOAT deletion have
differential effects on the hypothalamic-pituitary-adrenal axis and anxiety-like
behavior, suggesting that anxiety-like behavior in GOAT KO mice is not due to
high plasma des-acyl ghrelin.
PMID- 27490186
TI - Neuropsychiatric Presentation of Wilson Disease in an Adolescent Male.
PMID- 27490187
TI - Opening up the blackbox: an interpretable deep neural network-based classifier
for cell-type specific enhancer predictions.
AB - BACKGROUND: Gene expression is mediated by specialized cis-regulatory modules
(CRMs), the most prominent of which are called enhancers. Early experiments
indicated that enhancers located far from the gene promoters are often
responsible for mediating gene transcription. Knowing their properties,
regulatory activity, and genomic targets is crucial to the functional
understanding of cellular events, ranging from cellular homeostasis to
differentiation. Recent genome-wide investigation of epigenomic marks has
indicated that enhancer elements could be enriched for certain epigenomic marks,
such as, combinatorial patterns of histone modifications. METHODS: Our efforts in
this paper are motivated by these recent advances in epigenomic profiling
methods, which have uncovered enhancer-associated chromatin features in different
cell types and organisms. Specifically, in this paper, we use recent state-of-the
art Deep Learning methods and develop a deep neural network (DNN)-based
architecture, called EP-DNN, to predict the presence and types of enhancers in
the human genome. It uses as features, the expression levels of the histone
modifications at the peaks of the functional sites as well as in its adjacent
regions. We apply EP-DNN to four different cell types: H1, IMR90, HepG2, and HeLa
S3. We train EP-DNN using p300 binding sites as enhancers, and TSS and random non
DHS sites as non-enhancers. We perform EP-DNN predictions to quantify the
validation rate for different levels of confidence in the predictions and also
perform comparisons against two state-of-the-art computational models for
enhancer predictions, DEEP-ENCODE and RFECS. RESULTS: We find that EP-DNN has
superior accuracy and takes less time to make predictions. Next, we develop
methods to make EP-DNN interpretable by computing the importance of each input
feature in the classification task. This analysis indicates that the important
histone modifications were distinct for different cell types, with some overlaps,
e.g., H3K27ac was important in cell type H1 but less so in HeLa S3, while H3K4me1
was relatively important in all four cell types. We finally use the feature
importance analysis to reduce the number of input features needed to train the
DNN, thus reducing training time, which is often the computational bottleneck in
the use of a DNN. CONCLUSIONS: In this paper, we developed EP-DNN, which has high
accuracy of prediction, with validation rates above 90 % for the operational
region of enhancer prediction for all four cell lines that we studied,
outperforming DEEP-ENCODE and RFECS. Then, we developed a method to analyze a
trained DNN and determine which histone modifications are important, and within
that, which features proximal or distal to the enhancer site, are important.
PMID- 27490188
TI - Improved Sugar Puckering Profiles for Nicotinamide Ribonucleoside for Hybrid
QM/MM Simulations.
AB - The coenzyme nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH)
play ubiquitous roles as oxidizing and reducing agents in nature. The binding,
and possibly the chemical redox step, of NAD+/NADH may be influenced by the
cofactor conformational distribution and, in particular, by the ribose puckering
of its nicotinamide-ribonucleoside (NR) moiety. In many hybrid quantum mechanics
molecular mechanics (QM/MM) studies of NAD+/NADH dependent enzymes, the QM region
is treated by semiempirical (SE) methods. Recent work suggests that SE methods do
not adequately describe the ring puckering in sugar molecules. In the present
work we adopt an efficient and practical strategy to correct for this deficiency
for NAD+/NADH. We have implemented a cost-effective correction to a SE
Hamiltonian by adding a correction potential, which is defined as the difference
between an accurate benchmark density functional theory (DFT) potential energy
surface (PES) and the SE PES. In practice, this is implemented via a B-spline
interpolation scheme for the grid-based potential energy difference surface. We
find that the puckering population distributions obtained from free energy
QM(SE)/MM simulations are in good agreement with DFT and in fair accord with
experimental results. The corrected PES should facilitate a more accurate
description of the ribose puckering in the NAD+/NADH cofactor in simulations of
biological systems.
PMID- 27490189
TI - Notes from the Field: Fatal Infection Associated with Equine Exposure - King
County, Washington, 2016.
AB - On March 17, 2016, Public Health-Seattle & King County in Washington was notified
of two persons who received a diagnosis of Streptococcus equi subspecies
zooepidemicus (S. zooepidemicus) infections. S. zooepidemicus is a zoonotic
pathogen that rarely causes human illness and is usually associated with
consuming unpasteurized dairy products or with direct horse contact (1). In
horses, S. zooepidemicus is a commensal bacterium that can cause respiratory,
wound, and uterine infections (2). The health department investigated to
determine the magnitude of the outbreak, identify risk factors, and offer
recommendations.
PMID- 27490190
TI - Respiratory syncytial virus hospitalization outcomes and costs of full-term and
preterm infants.
AB - OBJECTIVE: Infection with respiratory syncytial virus (RSV), which causes lower
respiratory tract infections, is the leading cause of hospitalization among
children <1 year old in the United States. Risk factors for RSV hospitalization
include premature birth and younger chronologic age, along with several comorbid
conditions. However, in terms of RSV hospitalization costs, premature infants are
rarely studied separately from full-term infants. The objective of this study is
to describe the cost and severity of RSV hospitalizations among preterm and full
term infants without chronic lung disease or other high-risk conditions. STUDY
DESIGN: This analysis used Truven Health Market Scan Multi-State Medicaid and
Commercial Claims and Encounters databases, which contain a combined 4 million
births from 2003 to 2013. Infants with comorbid conditions associated with
increased risk for RSV infection were excluded. Infants were classified as
preterm (<29, 29-30, 31-32, 33-34 and 35-36 weeks' gestational age (wGA)) or full
term based on diagnostic coding. Health-care claims during the first year of life
were evaluated for RSV hospitalizations, defined as inpatient claims with a
diagnosis code for RSV in any position. Costs of RSV hospitalizations were
captured and reported in 2014 USD. Inpatient claims for RSV hospitalizations were
evaluated for the presence of codes indicating admission to the intensive care
unit (ICU), use of mechanical ventilation (MV) and length of stay. These three
measures were used to describe hospital severity. Chronologic age at the time of
RSV hospitalization was also captured. Data were summarized and no statistical
comparisons were conducted. RESULTS: There were 1 683 188 infants insured through
Medicaid and 1 663 832 infants insured through commercial plans born from 1 July
2003 to 30 June 2013. Of those, 10.8 and 8.8% in each database, respectively,
were born prematurely. There were 29 967 Medicaid-insured infants and 16 310
commercially insured infants with an RSV hospitalization during their first year
of life. Mean first-year RSV hospitalization costs were higher for preterm
infants, ranging from $8324 and $10 570 for full-term infants to $15 839 and $19
931 for preterm infants 33-34 wGA, and to $39 354 and $40 813 for preterm infants
<29 wGA, among Medicaid-insured and commercially insured infants, respectively.
RSV hospitalizations also tended to be more severe among preterm infants, with
longer lengths of stay, a higher proportion of infants admitted to the intensive
care unit (ICU) and increased use of MV compared with full-term infants. Mean
costs of RSV hospitalizations with a PICU admission ranged from approximately $35
000 to $89 000. In both Medicaid and commercial groups, costs were greater for
infants hospitalized at <90 days of age compared with older infants. CONCLUSIONS:
Infants who were born prematurely and those hospitalized at <90 days of age have
more costly and more severe RSV hospitalizations during the first year of life.
These findings demonstrate important differences in the costs and severity of
first-year RSV hospitalizations of premature and full-term infants. These
differences are likely to be obscured in combined analysis, in which full-term
infants predominate. Clinical guidelines and health-care policies relating to RSV
would benefit from the availability of data obtained from separate analyses of
these two infant subgroups.
PMID- 27490191
TI - Compassion fatigue, burnout and compassion satisfaction in neonatologists in the
US.
AB - OBJECTIVE: Compassion fatigue (CF) is distress experienced by caregivers from
ongoing contact with patients who are suffering. Burnout (BO) is occupational
stress directly related to dissonance between job demands and available
resources. Compassion satisfaction (CS) is professional fulfillment experienced
through helping others. CF in physicians is not well studied. Neonatologists may
be at particular risk for CF by virtue of recurrent exposure to distress in
patients and their families. The objectives of this study were to determine the
prevalence of CF, BO and CS, and to identify potential predictors for these
phenomena in neonatologists. STUDY DESIGN: A modified Compassion Fatigue and
Satisfaction Self-Test and a questionnaire of professional details and personal
characteristics were distributed electronically to neonatologists nationally.
Multivariable logistic and linear regression models for CF, BO and CS as a
function of potential predictors were constructed. RESULTS: The survey response
rate was 47%. The prevalence of CF, BO and CS was 15.7, 20.8 and 21.9%,
respectively. Female gender, emotional depletion, distress from 'a clinical
situation', 'co-workers', 'personal health issues' and 'not talking about
distressing issues' were each significant determinants of CF. Emotional
depletion, distress from the 'physical work environment' and 'co-workers', and
'not talking about distressing issues' were significant determinants of BO. Self
identification as Hispanic; 'not currently feeling distressed'; talking about
distressing issues; and utilization of pediatric palliative care services were
significant determinants of higher CS. CONCLUSIONS: CF and BO may impact
emotional well-being and professional performance of neonatologists. Enhancement
of CS is a potential target for intervention.
PMID- 27490192
TI - Transplacental passage of clindamycin from mother to neonate.
AB - OBJECTIVE: To evaluate maternal and neonatal cord blood levels at delivery in
patients receiving 900 mg of clindamycin intravenous (IV) every 8 h. STUDY
DESIGN: Prospective study consented every mother that entered labor with a
positive group B streptococcal culture, a high-risk penicillin allergy, and
sensitivity to clindamycin and erythromycin. Maternal and cord blood clindamycin
levels were obtained at delivery. Time from last dose completion to delivery,
number of doses administered and body mass index (BMI) were assessed. RESULTS:
Twenty-three patients were consented. All maternal clindamycin values were
therapeutic and 22 (96%) of the 23 cord blood samples were therapeutic. The mean
maternal level was of 4.46 MUg ml-1 (range of 0.7 to 8.4 MUg ml-1). The mean cord
blood level was 3.35 MUg ml-1 (range of <0.5 to 6.4 MUg ml-1). CONCLUSION: These
data show that the current dosing recommendation of 900 mg of clindamycin IV
every 8 h produces therapeutic maternal and cord blood levels.
PMID- 27490193
TI - Outcomes of Open-Approach Extracorporeal Septoplasty Without Simultaneous
Rhinoplasty: Effects on Nasal Tip Projection and Rotation.
AB - Importance: Performing an open-approach extracorporeal septoplasty (OAES) without
simultaneous rhinoplasty could have adverse effects. We sought to understand the
effects of OAES without simultaneous rhinoplasty on nasal tip projection and
rotation in patients with severe septal deviation. Objectives: To evaluate the
outcomes of OAES without simultaneous rhinoplasty in terms of nasal tip
projection and rotation using objective measurements. Design, Setting, and
Participants: This retrospective study was conducted at a training and research
hospital using medical records of 32 adult patients who underwent OAES without
simultaneous rhinoplasty between April 10, 2012 and June 12, 2015. Patients who
underwent endonasal septoplasty, revision septal surgery, septorhinoplasty, open
approach septoplasty with nasal tip plasty, or open-approach septoplasty without
removal of the entire septal cartilage were excluded from the study.
Postoperative photographs of the patients were taken at a mean (range) time of
16.4 (6-36) months after surgery. Nasolabial angle (NLA), nasofacial angle (NFA),
and projection index (PI) were measured by the same surgeon on preoperative and
postoperative lateral images. Main Outcomes and Measures: Projection index was
measured using the Goode method; NLA and NFA were measured drawing lines between
specific facial points according to the literature. All measurements were
compared statistically. Results: Thirty-two adult patients (26 men and 6 women
between ages 20 and 57 years) with severe septal deviation and underwent OAES
without simultaneous rhinoplasty were included in the study. The postoperative
values of NLA and NFA were observed to be decreased in all patients (100%). The
PI was also determined to be decreased in 27 patients (84.6%) whereas it remained
unchanged in 5 patients (15.4%). The overall postoperative mean values of NLA,
NFA, and PI were found to be lower compared with preoperative mean values and the
difference between them were determined to be statistically significant (NLA: 95%
CI, 0.40-2.55, P = .005; NFA: 95% CI, 0.48-2.06, P = .003; and PI: 95% CI, 0.004
0.015, P = .002). Conclusions and Relevance: This study reveals that the nasal
tip lost height from facial plane and rotated caudally in most patients who
underwent OAES without simultaneous rhinoplasty. Patients demanding only relief
of nasal obstruction and scheduled for OAES have to be informed about the
potential cosmetic alterations when a simultaneous rhinoplasty is not requested.
PMID- 27490194
TI - Association of Accelerometer-Assessed Sedentary Behavior With Diabetic
Retinopathy in the United States.
PMID- 27490195
TI - Zinc pyridinedicarboxylate micro-nanostructures: Promising anode materials for
lithium-ion batteries with excellent cycling performance.
AB - It is important to discover new, cheap and environmental friendly coordination
polymer electrode materials for lithium-ion batteries. Zinc 2,6
pyridilinedicarboxylate particles show better cycling stability and higher
discharge capacity than 2,5-pyridilinedicarboxylate micro-platelets when they are
firstly tested as anode materials for lithium-ion batteries. The former can
steadily cycle at current densities of 750, 1000 and 2000mAg(-1). It is also
stable in multiple insertion/extraction processes at current densities of 750,
1500, 2000, 2500, 3000, and 750mAg(-1), and the capacity retention is 77.9% after
60cycles. While the latter is apt to show good cycling performance at smaller
discharge current density.
PMID- 27490196
TI - Phase behaviour and non-monotonic film drying kinetics of aluminium chlorohydrate
glycerol-water ternary solutions.
AB - We study the drying and film formation of a model ternary system comprising an
inorganic salt (aluminium chlorohydrate, ACH), a humectant (glycerol) and water.
Employing viscometric, X-ray diffraction, calorimetric, dynamic vapour sorption,
spectroscopic, gravimetric and adhesion measurements, we examine the roles of
humectant concentration, temperature and relative humidity (RH) in the phase
behaviour and kinetics of film formation. Equilibrium film compositions are found
to be non-monotonic with glycerol content. Around 15:4 ACH:glycerol mass ratio,
films exhibit enhanced, albeit slower, desiccation, with water content lower than
that of binary ACH-water solutions. At higher glycerol content, drying is faster,
yet the resulting films have higher water content and remain tackier. Water
adsorption/desorption is shown to be fully reversible, and share a similar non
monotonic kinetic dependence on glycerol composition. These findings are
rationalised in terms of the competitive binding of water and glycerol to ACH,
the overall miscibility and glass formation within the ternary system. Our study
is relevant to a range of salt formulations, employed in a variety of commercial
applications, including lyoprotectants and personal care products.
PMID- 27490197
TI - Neuromotor Noise Is Malleable by Amplifying Perceived Errors.
AB - Variability in motor performance results from the interplay of error correction
and neuromotor noise. This study examined whether visual amplification of error,
previously shown to improve performance, affects not only error correction, but
also neuromotor noise, typically regarded as inaccessible to intervention. Seven
groups of healthy individuals, with six participants in each group, practiced a
virtual throwing task for three days until reaching a performance plateau. Over
three more days of practice, six of the groups received different magnitudes of
visual error amplification; three of these groups also had noise added. An
additional control group was not subjected to any manipulations for all six
practice days. The results showed that the control group did not improve further
after the first three practice days, but the error amplification groups continued
to decrease their error under the manipulations. Analysis of the temporal
structure of participants' corrective actions based on stochastic learning models
revealed that these performance gains were attained by reducing neuromotor noise
and, to a considerably lesser degree, by increasing the size of corrective
actions. Based on these results, error amplification presents a promising
intervention to improve motor function by decreasing neuromotor noise after
performance has reached an asymptote. These results are relevant for patients
with neurological disorders and the elderly. More fundamentally, these results
suggest that neuromotor noise may be accessible to practice interventions.
PMID- 27490198
TI - Madurella mycetomatis-Induced Massive Shoulder Joint Destruction: A Management
Challenge.
PMID- 27490199
TI - On the Nexus of the Spatial Dynamics of Global Urbanization and the Age of the
City.
AB - A number of concepts exist regarding how urbanization can be described as a
process. Understanding this process that affects billions of people and its
future development in a spatial manner is imperative to address related issues
such as human quality of life. In the focus of spatially explicit studies on
urbanization is typically a city, a particular urban region, an agglomeration.
However, gaps remain in spatially explicit global models. This paper addresses
that issue by examining the spatial dynamics of urban areas over time, for a full
coverage of the world. The presented model identifies past, present and potential
future hotspots of urbanization as a function of an urban area's spatial
variation and age, whose relation could be depicted both as a proxy and as a path
of urban development.
PMID- 27490200
TI - Measuring Poverty in Southern India: A Comparison of Socio-Economic Scales
Evaluated against Childhood Stunting.
AB - INTRODUCTION: Socioeconomic status (SES) scales measure poverty, wealth and
economic inequality in a population to guide appropriate economic and public
health policies. Measurement of poverty and comparison of material deprivation
across nations is a challenge. This study compared four SES scales which have
been used locally and internationally and evaluated them against childhood
stunting, used as an indicator of chronic deprivation, in urban southern India.
METHODS: A door-to-door survey collected information on socio-demographic
indicators such as education, occupation, assets, income and living conditions in
a semi-urban slum area in Vellore, Tamil Nadu in southern India. A total of 7925
households were categorized by four SES scales-Kuppuswamy scale, Below Poverty
Line scale (BPL), the modified Kuppuswamy scale, and the multidimensional poverty
index (MDPI) and the level of agreement compared between scales. Logistic
regression was used to test the association of SES scales with stunting.
FINDINGS: The Kuppuswamy, BPL, MDPI and modified Kuppuswamy scales classified
7.1%, 1%, 5.5%, and 55.3% of families as low SES respectively, indicating
conservative estimation of low SES by the BPL and MDPI scales in comparison with
the modified Kuppuswamy scale, which had the highest sensitivity (89%). Children
from low SES classified by all scales had higher odds of stunting, but the level
of agreement between scales was very poor ranging from 1%-15%. CONCLUSION: There
is great non-uniformity between existing SES scales and cautious interpretation
of SES scales is needed in the context of social, cultural, and economic
realities.
PMID- 27490201
TI - Genome Skimming: A Rapid Approach to Gaining Diverse Biological Insights into
Multicellular Pathogens.
PMID- 27490202
TI - Multiparametric serological testing in autoimmune encephalitis using computer
aided immunofluorescence microscopy (CAIFM).
AB - Autoantibodies against neuronal cell surface antigens are tightly associated with
immunotherapy-responsive autoimmune encephalitis, and a considerable number of
corresponding autoantigens has been identified in recent years. Most patients
initially present with overlapping symptoms, and a broad range of autoantibodies
has to be considered to establish the correct diagnosis and initiate treatment as
soon as possible to prevent irreversible and sometimes even life-threatening
damage to the brain. Recombinant cell-based immunofluorescence allows to
authentically present fragile membrane-associated surface antigens and, in
combination with multiparametric analysis in the form of biochip mosaics, has
turned out to be highly beneficial for parallel and prompt determination of anti
neuronal autoantibodies and comprehensive differential diagnostics. For the
evaluation of recombinant cell-based IIFT, a semi-automated novel function was
introduced into an established platform for computer-aided immunofluorescence
microscopy. The system facilitates the microscopic analysis of the tests and
supports the laboratory personnel in the rapid issuance of diagnostic findings,
which is of major importance for autoimmune encephalitis patients since timely
initiation of treatment may lead to their full recovery.
PMID- 27490203
TI - Multi-center harmonization of flow cytometers in the context of the European
"PRECISESADS" project.
AB - The innovative medicine initiative project called PRECISESADS will study 2.500
individuals affected by systemic autoimmune diseases (SADs) and controls. Among
extensive OMICS approaches, multi-parameter flow cytometry analyses will be
performed in eleven different centers. Therefore, the integration of all data in
common bioinformatical and biostatistical investigations requires a fine
mirroring of all instruments. We describe here the procedure elaborated to
achieve this prerequisite. One flow cytometer chosen as reference instrument
fixed the mean fluorescence intensities (MFIs) of 8 different fluorochrome
conjugated antibodies (Abs) using VersaComp Ab capture beads. The ten other
centers adjusted their own PMT voltages to reach the same MFIs. Subsequently, all
centers acquired Rainbow 8-peak beads data on a daily basis to follow the
stability of their instrument overtime. One blood sample has been dispatched and
concomitantly stained in all centers. Comparison of leukocytes frequencies and
cell surface marker MFIs demonstrated the close sensitivity of all flow
cytometers, allowing a multicenter analysis. The effective multi-center
harmonization enables the constitution of a workable wide flow cytometry database
for the identification of specific molecular signatures in individuals with SADs.
PMID- 27490204
TI - Critical review of the current recommendations for the treatment of systemic
inflammatory rheumatic diseases during pregnancy and lactation.
AB - The crucial issue for a better pregnancy outcome in women with autoimmune
rheumatic diseases is appropriate planning, with counseling of the ideal timing
and treatment adaptation. Drugs used to treat rheumatic diseases may interfere
with fertility or increase the risk of miscarriages and congenital abnormalities.
MTX use post-conception is clearly linked to abortions as well as major birth
defects, so it should be stopped 3months before conception. Leflunomide causes
abnormalities in animals even in low doses. Although in humans, it does not seem
to be as harmful as MTX, when pregnancy is detected in a patient on leflunomide,
cholestyramine is given for washout. Sulfasalazine can be used safely and is an
option for those patients who were on MTX or leflunomide. Azathioprine is
generally the immunosuppressive of choice in many high-risk pregnancy centers
because of the safety profile and its steroid-sparing property. Cyclosporine and
tacrolimus can also be used as steroid-sparing agents, but experience is smaller.
Although prednisone and prednisolone are inactivated in the placenta, we try to
limit the dose to the minimal effective one, to prevent side effects.
Antimalarials have been broadly studied and are safe during pregnancy and
breastfeeding. Among biologic disease modifying anti-rheumatic agents (bDMARD),
the anti-TNFs that have been used for longer are the ones with greater
experience. The large monoclonal antibodies do not cross the placenta in the
first trimester, and after conception, the decision to continue medication should
be taken individually. The experience is larger in women with inflammatory bowel
diseases, where anti-TNF is generally maintained at least until 30weeks to reduce
fetal exposure. Live vaccines should not be administrated to the infant in the
first 6months of life. Pregnancy data for rituximab, abatacept, anakinra,
tocilizumab, ustekinumab, belimumab, and tofacitinib are limited and their use in
pregnancy cannot currently be recommended.
PMID- 27490205
TI - From HBV to HPV: Designing vaccines for extensive and intensive vaccination
campaigns worldwide.
AB - HBsAg and HPV L1 proteins - the HBV and HPV antigens utilized in current vaccines
- share amino acid sequences with human proteins such as cardiomyopathy
associated protein 5, titin, protein-arginine deiminase, E3 ubiquitin-protein
ligase RNF19A, bassoon, G-protein coupled receptor for fatty acids, insulin
isoform 2, and mitogen-activated protein kinase kinase kinase 10, inter alia.
Many shared peptides are also part of immunopositive epitopes. The data 1)
support the possibility of crossreactions between the two viral antigens and
human proteins that, when altered, may associate with neuropsychiatric,
cardiovascular and metabolic diseases such as multiple sclerosis, amyotrophic
lateral sclerosis, diabetes, and sudden death; 2) confirm the concept that only
vaccines based on sequences unique to pathogens might nullify potential
crossreactivity risks in vaccination protocols.
PMID- 27490206
TI - Cardiovascular risk assessment in patients with rheumatoid arthritis: The
relevance of clinical, genetic and serological markers.
AB - Cardiovascular disease (CV) is the most common cause of premature mortality in
patients with rheumatoid arthritis (RA). This is the result of an accelerated
atherosclerotic process. Adequate CV risk stratification has special relevance in
RA to identify patients at risk of CV disease. However, current CV risk screening
and management strategies underestimate the actual CV risk in RA. Consequently,
the search for additional tools that may help to identify those patients at high
CV risk has become a key objective in the last years. In this regard, non
invasive surrogates, such as carotid ultrasonography, have been found to be
excellent predictors of future CV events. In addition, several studies have
revealed the relevance of a genetic component in the development of CV disease in
RA patients. Besides an association with HLA-DRB1* shared epitope alleles other
gene polymorphisms located inside and outside the HLA seem to influence the risk
of cardiovascular disease in RA. Moreover, serum levels of some metabolic
syndrome-related biomarkers, adipokines such as adiponectin and biomarkers of
endothelial cell activation and inflammation such as Osteoprotegerin and
Asymmetric dimethylarginine have recently been found useful for the prediction of
CV disease in these patients. An update of the current knowledge on these
potential markers, especially focused on new genetic and serological biomarkers
is shown in this review.
PMID- 27490207
TI - Transmission of Lamb waves and resonance at an adhesive butt joint of plates.
AB - The transmission behavior of Lamb waves and the possible occurrence of resonance
at an adhesive butt joint of plates are studied experimentally. To this purpose,
two 2.5-mm thick aluminum alloy plates are bonded at their edges using
cyanoacrylate-based adhesive. Bonded plate specimens with different joint
conditions are prepared by changing the bonding procedure. The measurements are
performed for the transmission characteristics of the lowest-order symmetric (S0)
and antisymmetric (A0) Lamb modes for the frequency range of 0.4-0.6MHz below the
cut-off frequency of the higher-order modes. The experimental results show that
the transmission coefficients of the S0 and A0 modes exhibit different frequency
dependent characteristics depending on the joint condition. Furthermore, for the
incidence of the S0 mode at the center frequency of 1MHz, the transmitted S0 mode
in weakly bonded specimens shows a long oscillation tail due to the resonance
effect. The experimental results are discussed in the light of the theoretical
results based on the spring-type interface model. The interfacial stiffnesses
identified from the transmission coefficients are shown to be correlated with the
bonding condition of the joint and give reasonable estimates of the resonance
frequencies of weakly bonded specimens.
PMID- 27490208
TI - Prediction of compound-target interactions of natural products using large-scale
drug and protein information.
AB - BACKGROUND: Verifying the proteins that are targeted by compounds of natural
herbs will be helpful to select natural herb-based drug candidates. However, this
entails a great deal of effort to clarify the interaction throughout in vitro or
in vivo experiments. In this light, in silico prediction of the interactions
between compounds and target proteins can help ease the efforts. RESULTS: In this
study, we performed in silico predictions of herbal compound target
identification. First, data related to compounds, target proteins, and
interactions between them are taken from the DrugBank database. Then we
characterized six classes of compound-target interaction in humans including G
protein-coupled receptors (GPCRs), ion channel, enzymes, receptors, transporters,
and other proteins. Also, classification-prediction models that predict the
interactions between compounds and target proteins through a machine learning
method were constructed using these matrices. As a result, AUC values of six
classes are 0.94, 0.93, 0.90, 0.89, 0.91, and 0.76 respectively. Finally, the
interactions of compounds from natural products were predicted using the
constructed classification models. Furthermore, from our predicted results, we
confirmed that several important disease related proteins were predicted as
targets of natural herbal compounds. CONCLUSIONS: We constructed classification
prediction models that predict the interactions between compounds and target
proteins. The constructed models showed good prediction performances, and numbers
of potential natural compounds target proteins were predicted from our results.
PMID- 27490209
TI - Effects of dietary green tea polyphenol supplementation on the health of workers
exposed to high-voltage power lines.
AB - Although it has been several decades since the focus on the effect of extremely
low frequency electromagnetic fields (ELF-EMF) of high-voltage power lines on
human health, no consistent conclusion has been drawn. The present study aimed to
investigate the change in oxidative stress after exposure to ELF-EMFs, and
potential protective effects of green tea polyphenol supplementation (GTPS) on
ELF-EMFs induced oxidative stress. A total of 867 subjects, including workers
with or without exposure to ELF-EMFs of 110-420kV power lines, participated and
were randomized into GTPS and placebo treatment groups. Oxidative stress and
oxidative damage to DNA were assessed by urinary tests of 8-isoprostane and 8
OHdG. Significant increased urinary 8-isoprostane and 8-OHdG were observed in
workers with ELF-EMFs exposure, which were diminished after 12 months of GTPS. No
protective effects of GTPS on oxidative stress and oxidative damage to DNA were
observed after three months of GTPS withdraw. We found a negative impact of high
voltage power lines on the health of workers. Long-term GTPS could be an
efficient protection against the health issues induced by high-voltage power
lines.
PMID- 27490210
TI - Effects of inducers of cytochrome P450s on enrofloxacin N-deethylation in crucian
carp Carassius auratus gibelio.
AB - In this study with crucian carp (Carassius auratus gibelio), the effect on
enrofloxacin (EF) and its metabolite ciprofloxacin (CF) and on the activity of
cytochrome P450 1A (CYP1A) and cytochrome P450 3A (CYP3A) was estimated following
the oral administration of rifampicin (RIF) (12mg/kg) and beta-naphthoflavone
(BNF) (12mg/kg), respectively. First, reversed-phase high-performance liquid
chromatography (RP-HPLC) was used to detect the pharmacokinetics of EF with
continual blood sampling. In RIF-treated, BNF-treated and control groups, the
value of the CmaxCF/CmaxEF ratio was 4.41, 0.81 and 0.95, and the corresponding
value of the AUC0-t-CF/AUC0-t-EF ratio was 3.69, 1.84 and 1.76, respectively. In
the RIF-treated, BNF-treated and control groups, the MRT values of EF were 26.57,
27.45 and 30.88h, and the corresponding values for CF were 5.79, 35.18 and
38.11h, respectively. Based on these results for crucian carp, the accumulation
and elimination of EF and CF in the RIF-treated group were more rapid than in BNF
treated and control groups. Second, liver microsomes were pretreated with the
inducer of CYP1A for BNF and that of CYP3A for RIF, and then the enzymatic
activities of CYP1A and CYP3A were measured, respectively. The activities of
ethoxyresorufin-O-deethylation (EROD) and erythromycin-N-demethylation (ERND)
increased significantly (P<0.05) for CYP1A and CYP3A, respectively. However, in
further experiments on the formation of CF, the level of EF N-deethylation was
significantly induced by RIF and inhibited by ketoconazole (KTZ) for CYP3A but
had no influence for CYP1A, BNF and berberine chloride (BER). We concluded that
CYP3A might be responsible for the N-deethylation of EF and because of this
activity, could also serve as a toxicity biomarker in crucian carp.
PMID- 27490211
TI - Tideglusib induces apoptosis in human neuroblastoma IMR32 cells, provoking sub
G0/G1 accumulation and ROS generation.
AB - Neuroblastoma is the most common tumor amongst children amounting to nearly 15%
of cancer deaths. This cancer is peculiar in its characteristics, exhibiting
differentiation, maturation and metastatic transformation leading to poor
prognosis and low survival rates among children. Chemotherapy, though toxic to
normal cells, has shown to improve the survival of the patient with emphasis
given more towards targeting angiogenesis. Recently, Tideglusib was designed as
an 'Orphan Drug' to target the neurodegenerative Alzheimer's disease and gained
significant momentum in its function during clinical trials. Duffy et al.
recently reported a reduction in cell viability of human IMR32 neuroblastoma
cells when treated with Tideglusib at varying concentrations. We investigated the
effects of Tideglusib, at various concentrations, compared to Lithium chloride at
various concentrations, on IMR32 cells. Lithium, a known GSK-3 inhibitor, was
used as a standard to compare the efficiency of Tideglusib in a dose-dependent
manner. Cell viability was assessed by MTT assay. The stages of apoptosis were
evaluated by AO/EB staining and nuclear damage was determined by Hoechst 33258
staining. Reactive oxygen species (ROS) and mitochondrial membrane potential
(DeltaPsim) were assessed by DCFDA dye and Rhodamine-123 dye, respectively.
Tideglusib reported a significant dose-dependent increase in pro-apoptotic
proteins (PARP, Caspase-9, Caspase-7, Caspase-3) and tumor-related genes (FasL,
TNF-alpha, Cox-2, IL-8, Caspase-3). Anti-GSK3 beta, pGSK3 beta, Bcl-2, Akt-1, p
Akt1 protein levels were observed with cells exposed to Tideglusib and Lithium
chloride. No significant dose-dependent changes were observed for the mRNA
expression of collagenase MMP-2, the tumor suppressor p53, or the cell cycle
protein p21. Our study also reports Tideglusib reducing colony formation and
increasing the level of sub-G0/G1 population in IMR32 cells. Our investigations
report the significance of Tideglusib as a promising apoptotic inducer in human
neuroblastoma IMR32 cells. Our study also reports that LiCl reduced cell
viability in IMR32 cells inducing apoptosis mediated by ROS generation.
PMID- 27490212
TI - Shape memory thermoplastic polyurethane (TPU)/poly(epsilon-caprolactone) (PCL)
blends as self-knotting sutures.
AB - Thermally responsive shape memory polymers have promising applications in many
fields, especially in biomedical areas. In this study, a simple method was
purposed to prepare thermoplastic polyurethane (TPU)/poly(epsilon-caprolactone)
(PCL) blends that possess shape memory attributes. TPU and PCL were melt
compounded via a twin-screw extruder and injection molded at various ratios.
Multiple test methods were used to characterize their shape memory properties and
reveal the underling mechanism. The blends containing 25% TPU and 75% PCL
possessed the best shape memory properties as indicated by a 98% shape fixing
ratio and 90% shape recovery ratio. This was attributed to the hybrid crystalline
and amorphous regions of PCL and TPU. We also found that PCL and TPU had good
miscibility and that the PCL domain in TPU25% had higher crystallinity than neat
PCL. The crystalline region in TPU25% could deform and maintain its temporary
shape when stretched, which contributed to its high shape fixing attribute, while
the rubbery TPU region assisted in the recovery of the sample upon heating by
releasing the deformation energy stored. Moreover, the TPU25% string prepared
could knot itself in a hot water bath, indicating a potential for suture
applications. Lastly, the 3T3 fibroblast cells cultured on the TPU/PCL blends
showed high viability and active substrate-cell interactions.
PMID- 27490213
TI - Chronic pain disorders after critical illness and ICU-acquired opioid dependence:
two clinical conundra.
AB - PURPOSE OF REVIEW: Is to describe the potential for patients to undergo an acute
to-chronic pain transition after ICU discharge as a result of pain they
experienced in ICU and to explore the phenomenon of ICU-acquired opioid
dependence. Both topics are timely, in that they can negatively influence patient
recovery after critical illness and contribute to post-ICU syndrome. RECENT
FINDINGS: Recognizing and treating pain in patients while they are in the ICU has
always been important. However, new knowledge increases the importance of good
pain management on patient welfare: recent basic science discoveries on
mechanisms of chronic pain development; identification of myriad factors,
occurring during the patient's hospital and ICU stay, that put patients at risk
for development of chronic pain; the view that a multimodal analgesia treatment
approach that is opioid sparing may be the optimum method for acute pain
management. Furthermore, recent findings about ICU-acquired opioid dependence
provide a foundation for promoting more rigorous assessment, prevention, and
treatment of opioid withdrawal in ICU patients. SUMMARY: Providing sufficient
analgesia to ICU patients while preventing opioid dependence and withdrawal is
essential to promote comfort and rehabilitation. Obtaining this balance requires
heightened ICU clinician attention and focused research.
PMID- 27490214
TI - Why are we Still Dialyzing Overdoses to Tricyclic Antidepressants? A subanalysis
of the NPDS database.
AB - A recent analysis of the American Association of Poison Control Centers database,
showed that poisonings from toxins not usually considered amenable to
extracorporeal purification ("non-classic toxins" such as ethanol and tricyclic
antidepressants) continue to be reported. This publication investigates factors
that may explain these findings. Our results suggest that: 1) the relatively high
absolute number of ECTR performed for non-classic toxins may simply reflect the
large number of exposures to these toxins, 2) poisoning from another toxin may
have been the reason for ECTR initiation in some exposures to non-classic toxins,
3) poisoning from non-classic toxins may receive ECTR for purposes other than
toxin removal, and 4) the decisional threshold to initiate ECTR may be lower for
non-classic toxins because of heightened toxicity.
PMID- 27490215
TI - Atraumatic Hip Instability.
AB - Atraumatic hip instability is an increasingly recognized source of pain and hip
dysfunction. It can result from numerous causes, including femoroacetabular
impingement, prior trauma, injury to the capsuloligamentous structures, and
idiopathic etiologies. Occult hip instability can be a challenging diagnosis that
requires careful attention to, and interpretation of, history, physical
examination, and radiographic imaging findings. Iatrogenic hip instability is a
potential complication of both open and arthroscopic hip-preserving surgical
procedures that can have catastrophic results. Atraumatic hip instability is a
pathologic entity that can be successfully addressed with open and arthroscopic
procedures.
PMID- 27490216
TI - Tendinopathy and Tendon Rupture Associated with Statins.
AB - Use of statins may be associated with certain tendinopathies and tendon ruptures,
especially of the Achilles, quadriceps, and distal biceps tendons. Tendinopathy
usually occurs within the first year of statin use and improves after the drug
therapy is stopped. Systemic conditions with a higher risk of tendon rupture
include diabetes, gout, rheumatoid arthritis, and chronic kidney disease. Certain
drugs, such as corticosteroids and fluoroquinolones, have also been implicated in
tendon ruptures. Patients with these systemic conditions who are taking statins
in combination with other drugs that increase the risk of tendon injury should be
educated about this risk and alternative treatments, including diet and exercise.
PMID- 27490217
TI - Problematic Pediatric Hand and Wrist Fractures.
AB - Seymour fractures are open juxta-physeal fractures of the distal phalanx. A true
lateral radiograph should be obtained for diagnosis, and treatment should include
removal of the nail, irrigation and debridement of the fracture, and percutaneous
Kirschner wire stabilization. Mallet fractures are more common in children than
adults, and treatment is generally nonoperative for nondisplaced or minimally
displaced fractures without volar subluxation of the distal phalanx; however,
splinting compliance should be carefully assessed in younger populations.
Phalangeal neck fractures have a limited potential to remodel and a propensity to
redisplace. A true lateral radiograph will show displacement best; treatment is
generally with percutaneous pinning. Open reduction should be avoided when
possible because of the risk of osteonecrosis of the phalangeal condyles. The
epidemiology of scaphoid fractures in children is changing, with waist fractures
now the most common type. This may be due to an increase in body mass index (BMI)
as well as high-level sports participation in today's pediatric population.
Although the vast majority of acute scaphoid fractures can be treated
successfully with cast immobilization, children who present with established
nonunions should be offered open reduction and internal fixation as the primary
treatment.
PMID- 27490218
TI - Introduction of New Technologies in Orthopaedic Surgery.
AB - The introduction of new devices, biologics, and combination products to the
orthopaedic marketplace is increasing rapidly. The majority of these new
technologies obtain clearance to market by demonstrating substantial equivalence
to a predicate (previously approved device) according to the U.S. Food and Drug
Administration (FDA) 510(k) process. Surgeons play a critical role in the
introduction of new technologies to patients and must take a leadership role in
promoting safe, efficacious, appropriate, and cost-effective care, especially for
operative procedures. Surgeons should monitor and document their patients'
clinical outcomes and adverse events when using new technology, to ensure that
the new technology is performing as desired.
PMID- 27490219
TI - Synovial Chondromatosis.
AB - Synovial chondromatosis is a rare, benign condition of unknown etiology in which
the synovium undergoes metaplasia leading to cartilaginous nodules that
ultimately break free, mineralize, and even ossify. The most commonly involved
joint is the knee. Patients may be asymptomatic or may present with pain,
swelling, and limited range of motion. Plain radiographs can be diagnostic and
mineralized nodules are pathognomonic. Recommended treatment involves
arthroscopic or open removal of loose bodies with or without a synovectomy to
prevent further articular and periarticular destruction and to relieve symptoms.
PMID- 27490220
TI - Operative Treatment of Lateral Ankle Instability.
AB - Chronic lateral ankle instability can occur in a subset of patients following
ankle inversion sprains. Operative treatment to restore stability in the ankle
and hindfoot and to prevent further degenerative changes may be indicated in
cases in which nonoperative treatment has failed. Anatomical direct repair with
use of native ligament remnants with or without reinforcement of the inferior
retinaculum is the so-called gold standard operative strategy for the treatment
of lateral ankle instability. The procedure has shown promising short and long
term outcomes. Candidates for the procedure have ligament remnants of sufficient
quality that are amendable to direct repair. Anatomical reconstruction with use
of autograft or allograft is reserved for patients with insufficient ligament
remnants to fashion a direct repair, failed previous lateral ankle repair, high
body mass index, or generalized ligamentous laxity. A wide variety of autografts
have been described, each with potential advantages and disadvantages. These
procedures can provide good-to-excellent short-term outcomes. However, there is
no available information on their long-term clinical results. Non-anatomical
lateral ligament reconstruction typically involves the use of the adjacent
peroneal brevis tendon and has been applied in cases in which only poor-quality
ligament remains. The procedure can provide good to excellent short-term
outcomes, although reported long-term outcomes have differed among studies. The
particular tendon used for the graft should be carefully considered given the
potential alterations in the kinematics of the ankle and hindfoot. Arthroscopic
ligament repair is becoming increasingly popular as it is minimally invasive.
This procedure is restricted to patients who have good-quality ligament remnants.
Good-to-excellent clinical outcomes have been reported after short and long-term
follow-up, although a relatively high rate of complications-including nerve
damage-has been reported following the procedure and therefore warrants further
investigation before widespread adoption can be advocated.
PMID- 27490221
TI - Design and validation of a near-infrared fluorescence endoscope for detection of
early esophageal malignancy.
AB - Barrett's esophagus is a known precursor lesion to esophageal adenocarcinoma. In
these patients, early detection of premalignant disease, known as dysplasia,
allows curative minimally invasive endoscopic therapy, but is confounded by a
lack of contrast in white light endoscopy. Imaging fluorescently labeled lectins
applied topically to the tissue has the potential to more accurately delineate
dysplasia, but tissue autofluorescence limits both sensitivity and contrast when
operating in the visible region. To overcome this challenge, we synthesized near
infrared (NIR) fluorescent wheat germ agglutinin (WGA-IR800CW) and constructed a
clinically translatable bimodal NIR and white light endoscope. Images of NIR and
white light with a field of view of 63 deg and an image resolution of 182 MUm
are coregistered and the honeycomb artifact arising from the fiber bundle is
removed. A minimum detectable concentration of 110 nM was determined using a
dilution series of WGA-IR800CW. We demonstrated ex vivo that this system can
distinguish between gastric and squamous tissue types in mouse stomachs
(p=0.0005) and accurately detect WGA-IR800CW fluorescence in human esophageal
resections (compared with a gold standard imaging system, rs>0.90). Based on
these findings, future work will optimize the bimodal endoscopic system for
clinical trials in Barrett's surveillance.
PMID- 27490222
TI - High-temporal-resolution, full-field optical angiography based on short-time
modulation depth for vascular occlusion tests.
AB - We developed high-temporal-resolution, full-field optical angiography for use in
vascular occlusion tests (VOTs). In the proposed method, undersampled signals are
acquired by a high-speed digital camera that separates the dynamic and static
speckle signals. The two types of speckle signal are used to calculate the short
time modulation depth (STMD) of each of the camera pixels. STMD is then used to
realize high-temporal-resolution, full-field optical angiography. Phantom and
biological experiments conducted and demonstrated the feasibility of using our
proposed method to perform VOTs and to study the reaction kinetics in
microfluidic systems.
PMID- 27490223
TI - An Unusual Case of Intra-Abdominal Air.
PMID- 27490224
TI - A Rare Cause of Ascites: Putting the Pieces....
PMID- 27490225
TI - A Rare Cause of Hepatitis: "Think Outta the Box!".
PMID- 27490226
TI - Hematuria and Diarrhea: A Case Report.
PMID- 27490227
TI - White Spots in the Rectum.
PMID- 27490228
TI - An Unusual Cause of Life-Threatening Upper Gastrointestinal Bleeding.
PMID- 27490229
TI - Unusual Gastric Nodules.
PMID- 27490230
TI - Appropriate Timing of Rectal Indomethacin Administration and Patient Selection in
Assessment of Post-ERCP Pancreatitis.
PMID- 27490231
TI - An Unusual Cause of Hematochezia and Aneurysmal Small Bowel Dilatation.
PMID- 27490232
TI - Statins for age-related macular degeneration.
AB - BACKGROUND: Age-related macular degeneration (AMD) is a progressive, late-onset
disorder of the macula affecting central vision. It is the leading cause of
blindness in people over 65 years in industrialized countries. Recent
epidemiologic, genetic, and pathological evidence has shown that AMD shares a
number of risk factors with atherosclerosis, leading to the hypothesis that
statins may exert protective effects in AMD. OBJECTIVES: The objective of this
review was to examine the effectiveness of statins compared with other
treatments, no treatment, or placebo in delaying the onset and progression of
AMD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register)
(2016, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed
Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2016),
EMBASE (January 1980 to March 2016), Latin American and Caribbean Health Sciences
Literature Database (LILACS) (January 1982 to March 2016), PubMed (January 1946
to March 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled
trials.com) (last searched 5 June 2014), ClinicalTrials.gov
(www.clinicaltrials.gov), and the WHO International Clinical Trials Registry
Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or
language restrictions in the electronic searches for trials. We last searched the
electronic databases on 31 March 2016. SELECTION CRITERIA: We included randomized
controlled trials (RCTs) and quasi-randomized trials that compared statins with
other treatments, no treatment, or placebo in people who were diagnosed as having
the early stages of AMD. DATA COLLECTION AND ANALYSIS: We used standard
methodological procedures expected by Cochrane. Two review authors independently
evaluated the search results against the selection criteria, abstracted data, and
assessed risk of bias. We did not perform meta-analysis due to heterogeneity in
the interventions and outcomes between the included studies. MAIN RESULTS: Two
RCTs with a total of 144 participants met the selection criteria. Both trials
compared simvastatin versus placebo in older people (older than 50 or 60 years)
with high risk of developing AMD (drusen present on examination). Overall, we
judged the quality of the evidence to be low, as we downgraded all outcomes due
to limitations in the designs of the trials and insufficient outcome reporting.
The larger trial, with 114 participants, was conducted in Australia and used a
higher dose (40 mg daily) of simvastatin for three years. Participants and study
personnel in this trial were adequately masked, however data were missing for 30%
of participants at three years' follow-up. The smaller trial, with 30
participants, was conducted in Italy and used a lower dose (20 mg) of simvastatin
for three months. This trial reported insufficient details to assess the risk of
bias.Neither trial reported data for change in visual acuity. Low-quality
evidence from the smaller trial, with 30 participants, did not show a
statistically significant difference between the simvastatin and placebo groups
in visual acuity values at three months of treatment (decimal visual acuity 0.21
+/- 0.56 in simvastatin group and 0.19 +/- 0.40 in placebo group) or 45 days
after the completion of treatment (decimal visual acuity 0.20 +/- 0.50 in
simvastatin group and 0.19 +/- 0.48 in placebo group). The lack of a difference
in visual acuity was not explained by lens or retina status, which remained
unchanged during and after the treatment period for both groups.Preliminary
analyses of 42 participants who had completed 12 months' follow-up in the larger
trial did not show a statistically significant difference between simvastatin and
the placebo groups for visual acuity, drusen score, or visual function (effect
estimates and confidence intervals were not available). Complete data for these
outcomes at three years' follow-up were not reported. At three years, low-quality
evidence showed an effect of simvastatin in slowing progression of AMD compared
with placebo to be uncertain (odds ratio 0.51, 95% confidence interval 0.23 to
1.09).One trial did not report adverse outcomes. The second trial reported no
difference between groups in terms of adverse events such as death, muscle aches,
and acute hepatitis. AUTHORS' CONCLUSIONS: Evidence from currently available RCTs
is insufficient to conclude that statins have a role in preventing or delaying
the onset or progression of AMD.
PMID- 27490233
TI - Atypical Radiological Presentation of a Wingless-Type Pediatric Medulloblastoma.
PMID- 27490234
TI - Consensus Statement of Society of Abdominal Radiology Disease-Focused Panel on
Barium Esophagography in Gastroesophageal Reflux Disease.
AB - OBJECTIVE: The Society of Abdominal Radiology established a panel to prepare a
consensus statement on the role of barium esophagography in gastroesophageal
reflux disease (GERD), as well as recommended techniques for performing the
fluoroscopic examination and the gamut of findings associated with this
condition. CONCLUSION: Because it is an inexpensive, noninvasive, and widely
available study that requires no sedation, barium esophagography may be performed
as the initial test for GERD or in conjunction with other tests such as
endoscopy.
PMID- 27490235
TI - Pediatric Chest Radiographs: Common and Less Common Errors.
AB - OBJECTIVE: Radiographic imaging of the pediatric chest presents several unique
challenges and nuances, stemming from congenital variants and pathologic
processes specific to this population. Errors in interpretation may lead to
inappropriate further imaging, incurring additional radiation exposure and cost,
as well as psychologic effects on the patients and their families. CONCLUSION:
Here, we aim to highlight some common and less common pitfalls in pediatric chest
radiography, as well as some tools for avoiding potential mistakes.
PMID- 27490236
TI - Orthogonal Dual-Triggered Shape-Memory DNA-Based Hydrogels.
AB - DNA-based shape-memory hydrogels revealing switchable shape recovery in the
presence of two orthogonal triggers are described. In one system, a shaped
DNA/acrylamide hydrogel is stabilized by duplex nucleic acids and pH-responsive
cytosine-rich, i-motif, bridges. Separation of the i-motif bridges at pH 7.4
transforms the hydrogel into a quasi-liquid, shapeless state, that includes the
duplex bridges as permanent shape-memory elements. Subjecting the quasi-liquid
state to pH 5.0 or Ag(+) ions recovers the hydrogel shape, due to the
stabilization of the hydrogel by i-motif or C-Ag(+) -C bridged i-motif. The
cysteamine-induced transformation of the duplex/C-Ag(+) -C bridged i-motif
hydrogel into a quasi-liquid shapeless state results in the recovery of the
shaped hydrogel in the presence of H(+) or Ag(+) ions as triggers. In a second
system, a shaped DNA/acrylamide hydrogel is generated by DNA duplexes and
bridging Pb(2+) or Sr(2+) ions-stabilized G-quadruplex subunits. Subjecting the
shaped hydrogel to the DOTA or KP ligands eliminates the Pb(2+) or Sr(2+) ions
from the respective hydrogels, leading to shapeless, memory-containing, quasi
liquid states that restore the original shapes with Pb(2+) or Sr(2+) ions.
PMID- 27490237
TI - Metal-Free Cross-Coupling of Arylboronic Acids and Derivatives with DAST-Type
Reagents for Direct Access to Diverse Aromatic Sulfinamides and Sulfonamides.
AB - We have developed a simple and convenient method for the cross-coupling of
arylboronic acids and their derivatives with DAST-type reagents under mild and
metal-free conditions to directly afford sulfinamides in moderate to good yields.
Moreover, sulfonamides were obtained after a simple oxidation reaction. The
reaction mechanism was investigated by (18) O-labeling experiments, and the
synthetic utility was demonstrated by the sulfoxidation of natural products.
PMID- 27490238
TI - Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases.
AB - Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have
variable symptoms and difficult diagnosis. In order to reclassify them based on
genetic markers rather than clinical criteria, we performed clustering of Single
Nucleotide Polymorphisms. However naive approaches tend to group patients
primarily by their geographic origin. To reduce this "ancestry signal", we
developed SNPClust, a method to select large sources of ancestry-independent
genetic variations from all variations detected by Principal Component Analysis.
Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust
successfully reduced the ancestry signal. Results were compared with association
studies between the cases and controls without or with reference population
stratification correction methods. SNPClust amplified the disease discriminating
signal and the ratio of significant associations outside the HLA locus was
greater compared to population stratification correction methods. SNPClust will
enable the use of ancestry-independent genetic information in the
reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R
package and demonstrated on the public Human Genome Diversity Project dataset at
https://github.com/ThomasChln/snpclust.
PMID- 27490239
TI - Enantioconvergent Nucleophilic Substitution Reaction of Racemic Alkyne-Dicobalt
Complex (Nicholas Reaction) Catalyzed by Chiral Bronsted Acid.
AB - Catalytic enantioselective syntheses enable a practical approach to
enantioenriched molecules. While most of these syntheses have been accomplished
by reaction at the prochiral sp(2)-hybridized carbon atom, little attention has
been paid to enantioselective nucleophilic substitution at the sp(3)-hybridized
carbon atom. In particular, substitution at the chiral sp(3)-hybridized carbon
atom of racemic electrophiles has been rarely exploited. To establish an
unprecedented enantioselective substitution reaction of racemic electrophiles,
enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from
racemic propargylic alcohol was developed using a chiral phosphoric acid
catalyst. In the present enantioconvergent process, both enantiomers of the
racemic alcohol were transformed efficiently to a variety of thioethers with high
enantioselectivity. The key to achieving success is dynamic kinetic asymmetric
transformation (DYKAT) of enantiomeric cationic intermediates generated via
dehydroxylation of the starting racemic alcohol under the influence of the chiral
phosphoric acid catalyst. The present fascinating DYKAT involves the efficient
racemization of these enantiomeric intermediates and effective resolution of
these enantiomers through utilization of the chiral conjugate base of the
phosphoric acid.
PMID- 27490241
TI - The Ramachandran Number: An Order Parameter for Protein Geometry.
AB - Three-dimensional protein structures usually contain regions of local order,
called secondary structure, such as alpha-helices and beta-sheets. Secondary
structure is characterized by the local rotational state of the protein backbone,
quantified by two dihedral angles called phi and psi. Particular types of
secondary structure can generally be described by a single (diffuse) location on
a two-dimensional plot drawn in the space of the angles phi and psi, called a
Ramachandran plot. By contrast, a recently-discovered nanomaterial made from
peptoids, structural isomers of peptides, displays a secondary-structure motif
corresponding to two regions on the Ramachandran plot [Mannige et al., Nature
526, 415 (2015)]. In order to describe such 'higher-order' secondary structure in
a compact way we introduce here a means of describing regions on the Ramachandran
plot in terms of a single Ramachandran number, [Formula: see text], which is a
structurally meaningful combination of phi and psi. We show that the potential
applications of [Formula: see text] are numerous: it can be used to describe the
geometric content of protein structures, and can be used to draw diagrams that
reveal, at a glance, the frequency of occurrence of regular secondary structures
and disordered regions in large protein datasets. We propose that [Formula: see
text] might be used as an order parameter for protein geometry for a wide range
of applications.
PMID- 27490240
TI - KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are
Associated with Vogt-Koyanagi-Harada Disease.
AB - Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer
lymphocytes that provide defense against viral infections and tumor
transformation. Analogous to that of CTL, interactions of killer-cell
immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA)
class I ligands calibrate NK cell education and response. Gene families encoding
KIRs and HLA ligands are located on different chromosomes, and feature variation
in the number and type of genes. The independent segregation of KIR and HLA genes
results in variable KIR-HLA interactions in individuals, which may impact disease
susceptibility. We tested whether KIR-HLA combinations are associated with Vogt
Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has
strong association with HLA-DR4. We present a case control study of 196 VKH
patients and 209 controls from a highly homogeneous native population of Japan.
KIR and HLA class I genes were typed using oligonucleotide hybridization method
and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx
KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007),
due primarily to a decrease in centromeric B-KIR motif and its associated KIRs
2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was
increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was
decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and
3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49,
P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA
combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more
common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic
hyporesponsiveness of NK cells (due to poor NK education along with missing of
activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective
immune response against viral-infection that may trigger VKH pathogenesis in
genetically susceptible individuals, such as HLA-DR4 carriers.
PMID- 27490242
TI - Prevalence and Phylogenetic Analysis of Human Bocaviruses 1-4 in Pediatric
Patients with Various Infectious Diseases.
AB - OBJECTIVES: Viral infections caused by human bocaviruses 1-4 (HBoV1-4) are more
complicated than previously believed. A retrospective, large-scale study was
undertaken to explore the prevalence of HBoV1-4 in pediatric patients with
various infectious diseases and delineate their phylogenetic characteristics.
METHODS: Clinical samples from four specimen types, including 4,941 respiratory,
2,239 cerebrospinal fluid (CSF), 2,619 serum, and 1,121 fecal specimens,
collected from pediatric patients with various infectious diseases were screened
for HBoV1-4. A 690-nt fragment in each specimen was then amplified and sequenced
for phylogenetic analysis. Clinical characteristics of HBoV-positive patients
with different specimen types available were evaluated. RESULTS: Approximately
1.2% of patients were confirmed as HBoV-positive, with the highest positive rate
in patients with gastrointestinal infection (2.2%), followed by respiratory
(1.65%), central nervous system (0.8%), and hematological infections (0.2%). A
single genetic lineage of HBoV1 circulated among children over the 8-year period,
while a new cluster of HBoV2, via intra-genotype recombination between HBoV2A and
HBoV2B, was prevalent. Some patients had HBoV1-positive respiratory and serum
specimens or fecal specimens. Several cases became HBoV1-positive following the
appearance of respiratory infection, while several cases were positive for HBoV2
only in CSF and serum specimens, rather than respiratory specimens. CONCLUSIONS:
A single genetic lineage of HBoV1 is speculated as a viral pathogen of
respiratory infection and causes both comorbid infection and acute
gastroenteritis. Additionally, a new cluster of HBoV2 is prevalent in China,
which may infect the host through sites other than the respiratory tract.
PMID- 27490244
TI - Effect of Additives on the Selectivity and Reactivity of Enzymes.
AB - Enzymes have been widely used as efficient, eco-friendly, and biodegradable
catalysts in organic chemistry due to their mild reaction conditions and high
selectivity and efficiency. In recent years, the catalytic promiscuity of many
enzymes in unnatural reactions has been revealed and studied by chemists and
biochemists, which has expanded the application potential of enzymes. To enhance
the selectivity and activity of enzymes in their natural or promiscuous
reactions, many methods have been recommended, such as protein engineering,
process engineering, and media engineering. Among them, the additive approach is
very attractive because of its simplicity to use and high efficiency. In this
paper, we will review the recent developments about the applications of additives
to improve the catalytic performances of enzymes in their natural and promiscuous
reactions. These additives include water, organic bases, water mimics,
cosolvents, crown ethers, salts, surfactants, and some particular molecular
additives.
PMID- 27490243
TI - N-glycosylation in the thermoacidophilic archaeon Sulfolobus acidocaldarius
involves a short dolichol pyrophosphate carrier.
AB - N-glycosylation is a post-translational modification that occurs across
evolution. In the thermoacidophilic archaea Sulfolobus acidocaldarius,
glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent
of the N-glycans assembled in Eukarya. Previously, hexose-bearing dolichol
phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. Here, we
used a specialized protocol for extracting lipid-linked oligosaccharides to
detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its
biosynthetic intermediates. Furthermore, evidence for N-glycosylation of two S.
acidocaldarius proteins by the same hexasaccharide and its derivatives was
collected. These findings thus provide novel insight into archaeal N
glycosylation.
PMID- 27490245
TI - Outcome after ileal pouch-anal anastomosis in ulcerative colitis patients:
experience during a 27-year period.
AB - BACKGROUND: No previous study describes the postoperative outcome and functional
results after ileal pouch-anal anastomosis (IPAA), performed in ulcerative
colitis by the same surgical team with the different anastomotic techniques
adopted in a 27-year period. METHODS: Prospectively, consecutive 333 ulcerative
colitis patients operated adopting different IPAA techniques during the open
surgery period 1984-2011 were enrolled. IPAA was performed using single stapling
(SS) technique in 38 patients, double stapling (DS) technique in 235 patients
(TIA stapler 42 patients, Endo-GIA 131 patients, Contour 62 patients) and
handsewn IPAA in 60 patients. RESULTS: Statistically different early and late
complications were recorded among the different IPAA techniques. A lower
frequency of daily and nocturnal defecations and a higher level of continence
were observed in the DS-IPAA compared to handsewn IPAA. The distance between the
anastomotic line and the anal verge was significantly lower in DS Endo-GIA or DS
Contour groups than in the DS TIA and SS. In SS IPAA group, 31.6% developed
cuffitis compared to 14.4% belonging to DS group, at a mean follow-up of 140.4
months. CONCLUSIONS: Technical improvements changed the IPAA technique. Stapled
IPAA is characterized by better functional outcome than handsewn IPAA. DS Endo
GIA and Contour IPAA are followed by lower risk of cuffitis.
PMID- 27490246
TI - High-rate, High Temperature Acetotrophic Methanogenesis Governed by a Three
Population Consortium in Anaerobic Bioreactors.
AB - A combination of acetate oxidation and acetoclastic methanogenesis has been
previously identified to enable high-rate methanogenesis at high temperatures (55
to 65 degrees C), but this capability had not been linked to any key organisms.
This study combined RNA-stable isotope probing on 13C-labelled acetate and 16S
amplicon sequencing to identify the active micro-organisms involved in high-rate
methanogenesis. Active biomass was harvested from three bench-scale thermophilic
bioreactors treating waste activated sludge at 55, 60 and 65 degrees C, and fed
with 13-C labelled and 12C-unlabelled acetate. Acetate uptake and cumulative
methane production were determined and kinetic parameters were estimated using
model-based analysis. Pyrosequencing performed on 13C- enriched samples indicated
that organisms accumulating labelled carbon were Coprothermobacter (all
temperatures between 55 and 65 degrees C), acetoclastic Methanosarcina (55 to 60
degrees C) and hydrogenotrophic Methanothermobacter (60 to 65 degrees C). The
increased relative abundance of Coprothermobacter with increased temperature
corresponding with a shift to syntrophic acetate oxidation identified this as a
potentially key oxidiser. Methanosarcina likely acts as both a hydrogen utilising
and acetoclastic methanogen at 55 degrees C, and is replaced by
Methanothermobacter as a hydrogen utiliser at higher temperatures.
PMID- 27490247
TI - Quantitatively Verifying the Results' Rationality for Farmland Quality Evaluation
with Crop Yield, a Case Study in the Northwest Henan Province, China.
AB - Evaluating the assessing results' rationality for farmland quality (FQ) is
usually qualitative and based on farmers and experts' perceptions of soil quality
and crop yield. Its quantitative checking still remains difficult and is likely
ignored. In this paper, FQ in Xiuwu County, the Northwest Henan Province, China
was evaluated by the gray relational analysis (GRA) method and the traditional
analytic hierarchy process (AHP) method. The consistency rate of two results was
analysed. Research focused on proposing one method of testing the evaluation
results' rationality for FQ based on the crop yield. Firstly generating a grade
map of crop yield and overlying it with the FQ evaluation maps. Then analysing
their consistency rate for each grade in the same spatial position. Finally
examining the consistency effects and allowing for a decision on adopting the
results. The results showed that the area rate consistency and matching
evaluation unit numbers between the two methods were 84.68% and 87.29%,
respectively, and the space distribution was approximately equal. The area
consistency rates between crop yield level and FQ evaluation levels by GRA and
AHP were 78.15% and 74.29%, respectively. Therefore, the verifying effects of GRA
and AHP were near, good and acceptable, and the FQ results from both could
reflect the crop yield levels. The evaluation results by GCA, as a whole, were
slightly more rational than that by AHP.
PMID- 27490248
TI - Copper-Catalyzed Oxirane-Opening Reaction with Aryl Iodides and Se Powder.
AB - Using Se powder as the selenating reagent, the copper-catalyzed double C-Se cross
coupling of aryl iodides, epoxides, and elemental selenium has been developed.
This strategy provides a straightforward approach to the synthesis of beta
hydroxy phenylselenides with excellent regioselectivity of the ring opening
reaction. This process proceeds in generally good yields and is compatible with a
broad range of functional groups.
PMID- 27490249
TI - The HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening
of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS).
AB - BACKGROUND: The major adverse consequences of obesity are associated with the
development of insulin resistance (IR) and adiposopathy. The Homeostasis Model
Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1
IR, which incorporates adiponectin in the denominator of the index. OBJECTIVES:
To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index
as a surrogate marker of IR in women, and to establish the cutoff value of the
HOMA-AD. SUBJECTS/METHODS: The Brazilian Metabolic Syndrome Study (BRAMS) is a
cross-sectional multicenter survey. The data from 1,061 subjects met the desired
criteria: 18-65 years old, BMI: 18.5-49.9 Kg/m2 and without diabetes. The IR was
assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the
hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF
criteria. RESULTS: For the IR assessed by the clamp, the HOMA-AD demonstrated a
stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r =
0.56); p < 0.0001. In the ROC analysis, compared with the HOMA1-IR, the HOMA-AD
showed higher values of the AUC for the identification of IR based on the clamp
test (AUC: 0.844 vs. AUC: 0.804) and on the metabolic syndrome (AUC: 0.703 vs.
AUC: 0.689), respectively; p < 0.001 for all. However, the pairwise comparison
did not show evidence of superiority for the HOMA-AD in comparison with the HOMA1
IR in the diagnosis of IR and metabolic syndrome (p > 0.05). The optimal cutoff
identified for the HOMA-AD for the diagnosis of IR was 0.95. CONCLUSIONS: The
HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR
among adult women and presented a similar performance compared with the HOMA1-IR
index. These results may assist physicians and researchers in determining which
method to use to evaluate IR in light of the available facilities.
PMID- 27490250
TI - Characteristic microglial features in patients with hereditary diffuse
leukoencephalopathy with spheroids.
AB - OBJECTIVE: To clarify the histopathological alterations of microglia in the
brains of patients with hereditary diffuse leukoencephalopathy with spheroids
(HDLS) caused by mutations of the gene encoding the colony stimulating factor-1
receptor (CSF-1R). METHODS: We examined 5 autopsied brains and 1 biopsy specimen
from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical,
biochemical, and ultrastructural features of microglia were examined, and
quantitative analyses were performed. RESULTS: In layers 3 to 4 of the frontal
cortex in HDLS brains, microglia showed relatively uniform and delicate
morphology, with thin and winding processes accompanying knotlike structures, and
significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1
positive cells were evident in comparison with control brains. On the other hand,
in layers 5 to 6 and the underlying white matter, microglia were distributed
unevenly; that is, in some areas they had accumulated densely, whereas in others
they were scattered. Immunoblot analyses of microglia-associated proteins,
including CD11b and DAP12, revealed that HDLS brains had significantly lower
amounts of these proteins than diseased controls, although Ki-67-positive
proliferative microglia were not reduced. Ultrastructurally, the microglial
cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic
reticulum and disaggregated polyribosomes, indicating depression of protein
synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or
P2ry12, indicating that they were derived from bone marrow. INTERPRETATION: The
pathogenesis of HDLS seems to be associated with microglial vulnerability and
morphological alterations. Ann Neurol 2016;80:554-565.
PMID- 27490252
TI - The Thrower's Shoulder: An Update.
PMID- 27490251
TI - The Representation of Prediction Error in Auditory Cortex.
AB - To survive, organisms must extract information from the past that is relevant for
their future. How this process is expressed at the neural level remains unclear.
We address this problem by developing a novel approach from first principles. We
show here how to generate low-complexity representations of the past that produce
optimal predictions of future events. We then illustrate this framework by
studying the coding of 'oddball' sequences in auditory cortex. We find that for
many neurons in primary auditory cortex, trial-by-trial fluctuations of neuronal
responses correlate with the theoretical prediction error calculated from the
short-term past of the stimulation sequence, under constraints on the complexity
of the representation of this past sequence. In some neurons, the effect of
prediction error accounted for more than 50% of response variability. Reliable
predictions often depended on a representation of the sequence of the last ten or
more stimuli, although the representation kept only few details of that sequence.
PMID- 27490253
TI - Osseous Sarcoidosis.
PMID- 27490254
TI - Acute Achilles Tendon Rupture: A Critical Analysis Review.
PMID- 27490255
TI - Degenerative Lumbar Scoliosis.
PMID- 27490256
TI - Silica Wastes to High-Performance Lithium Storage Materials: A Rational Designed
Al2 O3 Coating Assisted Magnesiothermic Process.
AB - Si/C yolk-shell structures have been developed to deal with the major issues
associated with Si anodes: the huge volume changes and the low electrical
conductivity. However, the fabrication process often involves expensive starting
materials and/or simultaneously generates insulated SiC, which is harmful for Si
anodes. Here, silica wastes from the optical fibers industry are used as starting
materials to prepare high performance Si/C materials with Si@void@C yolk-shell
structure via a rational designed Al2 O3 coating assisted magnesiothermic
process. The obtained yolk-shell Si@void@C materials have a capacity of more than
1450 mA h g-1 after 100 cycles at 0.4 A g-1 . Thanks to the easily coated and
removed Al2 O3 layer, the general formation of SiC can be avoided which is
beneficial for improving the rate performances, and a capacity of ~800 mA h g-1
is still kept after 200 cycles at a high rate of 10 A g-1 with a low capacity
loss of 0.08% per cycle.
PMID- 27490257
TI - Changes in Dietary Fat Intake and Projections for Coronary Heart Disease
Mortality in Sweden: A Simulation Study.
AB - OBJECTIVE: In Sweden, previous favourable trends in blood cholesterol levels have
recently levelled off or even increased in some age groups since 2003,
potentially reflecting changing fashions and attitudes towards dietary saturated
fatty acids (SFA). We aimed to examine the potential effect of different SFA
intake on future coronary heart disease (CHD) mortality in 2025. METHODS: We
compared the effect on future CHD mortality of two different scenarios for fat
intake a) daily SFA intake decreasing to 10 energy percent (E%), and b) daily SFA
intake rising to 20 E%. We assumed that there would be moderate improvements in
smoking (5%), salt intake (1g/day) and physical inactivity (5% decrease) to
continue recent, positive trends. RESULTS: In the baseline scenario which assumed
that recent mortality declines continue, approximately 5,975 CHD deaths might
occur in year 2025. Anticipated improvements in smoking, dietary salt intake and
physical activity, would result in some 380 (-6.4%) fewer deaths (235 in men and
145 in women). In combination with a mean SFA daily intake of 10 E%, a total of
810 (-14%) fewer deaths would occur in 2025 (535 in men and 275 in women). If the
overall consumption of SFA rose to 20 E%, the expected mortality decline would be
wiped out and approximately 20 (0.3%) additional deaths might occur. CONCLUSION:
CHD mortality may increase as a result of unfavourable trends in diets rich in
saturated fats resulting in increases in blood cholesterol levels. These could
cancel out the favourable trends in salt intake, smoking and physical activity.
PMID- 27490258
TI - Assessment of the Broader Economic Consequences of HPV Prevention from a
Government-Perspective: A Fiscal Analytic Approach.
AB - BACKGROUND: Cervical cancer poses a substantial burden in terms of morbidity,
mortality, and economic losses, especially in low/middle-income countries. HPV
vaccination and/or cervical cancer screening among females may reduce the burden
of HPV-related diseases, including cervical cancer. However, limited funds may
impede the implementation of population-based programmes. Governmental
investments in the prevention of infectious disease may have broader economic and
fiscal benefits, which are not accounted in conventional economic analyses. This
study estimates the broader economic and fiscal impacts of implementing HPV
vaccination and/or cervical cancer screening in Indonesia from the perspective of
the government. METHODS: A government-perspective quantitative analytic framework
was applied to assess the Net Present Value (NPV) of investment on cervical
cancer prevention strategies including HPV vaccination, cervical screening and
its combination in Indonesia. All monetary values were presented in International
Dollars (I$). RESULTS: Based on a cohort of 10,000,000 Indonesian 12-year-old
females, it was estimated that HPV vaccination and/or cervical cancer screening
result in a positive NPV for the Indonesian government. The combination of
cervical screening and HPV vaccination generated a substantial reduction of
cervical cancer incidence and HPV-related mortality of 87,862 and 19,359,
respectively. It was estimated that HPV vaccination in combination with cervical
screening is the most favorable option for cervical cancer prevention (NPV
I$2.031.786.000), followed by HPV vaccination alone (NPV I$1.860.783.000) and
cervical screening alone (NPV I$375.244.000). CONCLUSION: In addition to clinical
benefits, investing in HPV vaccination and cervical screening may yield
considerable fiscal benefits for the Indonesian governments due to lifelong
benefits resulting from reduction of cervical cancer-related morbidity and
mortality.
PMID- 27490260
TI - Proceedings of the 8th Annual Conference on the Science of Dissemination and
Implementation : Washington, DC, USA. 14-15 December 2015.
PMID- 27490259
TI - Apicoplast-Localized Lysophosphatidic Acid Precursor Assembly Is Required for
Bulk Phospholipid Synthesis in Toxoplasma gondii and Relies on an Algal/Plant
Like Glycerol 3-Phosphate Acyltransferase.
AB - Most apicomplexan parasites possess a non-photosynthetic plastid (the
apicoplast), which harbors enzymes for a number of metabolic pathways, including
a prokaryotic type II fatty acid synthesis (FASII) pathway. In Toxoplasma gondii,
the causative agent of toxoplasmosis, the FASII pathway is essential for parasite
growth and infectivity. However, little is known about the fate of fatty acids
synthesized by FASII. In this study, we have investigated the function of a plant
like glycerol 3-phosphate acyltransferase (TgATS1) that localizes to the T.
gondii apicoplast. Knock-down of TgATS1 resulted in significantly reduced
incorporation of FASII-synthesized fatty acids into phosphatidic acid and
downstream phospholipids and a severe defect in intracellular parasite
replication and survival. Lipidomic analysis demonstrated that lipid precursors
are made in, and exported from, the apicoplast for de novo biosynthesis of bulk
phospholipids. This study reveals that the apicoplast-located FASII and ATS1,
which are primarily used to generate plastid galactolipids in plants and algae,
instead generate bulk phospholipids for membrane biogenesis in T. gondii.
PMID- 27490261
TI - Internal Concentration and Time Are Important Modifiers of Toxicity: The Case of
Chlorpyrifos on Caenorhabditis elegans.
AB - The internal concentration of chemicals in exposed organisms changes over time
due to absorption, distribution, metabolism, and excretion processes since
chemicals are taken up from the environment. Internal concentration and time are
very important modifiers of toxicity when biomarkers are used to evaluate the
potential hazards and risks of environmental pollutants. In this study, the
responses of molecular biomarkers, and the fate of chemicals in the body, were
comprehensively investigated to determine cause-and-effect relationships over
time. Chlorpyrifos (CP) was selected as a model chemical, and Caenorhabditis
elegans was exposed to CP for 4 h using the passive dosing method. Worms were
then monitored in fresh medium during a 48-h recovery regime. The mRNA expression
of genes related to CYP metabolism (cyp35a2 and cyp35a3) increased during the
constant exposure phase. The body residue of CP decreased once it reached a peak
level during the early stage of exposure, indicating that the initial uptake of
CP rapidly induced biotransformation with the synthesis of new CYP metabolic
proteins. The residual chlorpyrifos-oxon concentration, an acetylcholinesterase
(AChE) inhibitor, continuously increased even after the recovery regime started.
These delayed toxicokinetics seem to be important for the extension of AChE
inhibition for up to 9 h after the start of the recovery regime. Comprehensive
investigation into the molecular initiation events and changes in the internal
concentrations of chemical species provide insight into response causality within
the framework of an adverse outcome pathway.
PMID- 27490262
TI - Nanoparticle Assembly of Surface-Modified Proteins.
AB - Nature's biomaterials such as peptides and proteins represent a valuable source
of highly defined macromolecules. Herein we developed a nanoparticle drug
delivery system based on the assembly of surface-modified proteins that can be
transferred into organic solvents and represent the structural material of the
carrier system. The particles are prepared by an oil-in-water nanoemulsion
technique without the need of additional denaturation or cross-linking steps for
stabilization. We achieve the necessary lipophilic solubility switch of the
protein material by high surface PEGylation under conservation of the native
three-dimensional protein structure. This study focuses on lysozyme as model
enzyme for the preparation of empty and doxorubicin-loaded nanoparticles with an
average diameter of 100 nm. The particles are stable in physiological buffers and
only release their therapeutic payload into cancer cells after a time-dependent
cellular uptake. We also transferred this approach to various proteins,
exemplifying the universal applicability of our new preparation method for
protein-based nanoparticles.
PMID- 27490263
TI - The association of dopamine pathway gene score, nicotine dependence and smoking
cessation in a rural male population of Shandong, China.
AB - BACKGROUND AND OBJECTIVES: Smoking and smoking cessation are both psychological
and physiological traits. We aimed to investigate the interaction between
dopamine pathway gene scores and nicotine dependence on smoking cessation in a
rural Chinese male population. METHODS: Participants were recruited from 17
villages in Shandong, China. DNA was extracted from blood sample of 819
participants. 25 single nucleotide polymorphisms (SNPs) in 8 dopamine (DA)
pathway genes were genotyped. Weighted gene score of each gene is used to analyze
the whole gene effect. Logistic regression was used to calculate odds ratios (OR)
and multivariate-adjusted OR of each gene score for smoking cessation.
Multiplicative model interaction was assessed through a cross-product interaction
term of gene score by nicotine dependence in a multivariate logistic regression
model. RESULTS: After adjusting for age, occupation, education, marital status,
self-rating anxiety score, and disease status, we observed significant negative
associations of catechol-O-methyltransferase (COMT), dopamine receptor D2 (DRD2)
gene score and smoking cessation, as well as significant positive associations
between ankyrin repeat and kinase domain containing 1 (ANKK1), dopamine
transporter (SLC6A3), dopamine receptor D4 (DRD4) gene score and smoking
cessation. A significant multiplicative model interaction between nicotine
dependence and the SLC6A3 gene score on smoking cessation was also observed (p =
.03). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: There is a significant
multiplicative model interaction of SLC6A3 gene score and nicotine dependence on
smoking cessation. This finding could help to identify smokers who may be at high
risk of relapse, and thus to develop more professional and personalized smoking
cessation treatment. (Am J Addict 2016;25:493-498).
PMID- 27490265
TI - Pharmacogenetics of cystic fibrosis treatment.
AB - Cystic fibrosis (CF) is genetic autosomal recessive disease caused by reduced or
absent function of CFTR protein. Treatments for patients with CF have primarily
focused on the downstream end-organ consequences of defective CFTR. Since the
discovery of the CFTR gene that causes CF in 1989 there have been tremendous
advances in our understanding of the genetics and pathophysiology of CF. This has
recently led to the development of new CFTR mutation-specific targeted therapies
for select patients with CF. This review will discuss the characteristics of the
CFTR gene, the CFTR mutations that cause CF and the new mutation specific
pharmacological treatments including gene therapy that are contributing to the
dawning of a new era in cystic fibrosis care.
PMID- 27490266
TI - Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory
stress-induced senescence features of osteoarthritic chondrocytes.
AB - Aging and exposure to stress would determine the chondrocyte phenotype in
osteoarthritis (OA). In particular, chronic inflammation may contribute to stress
induced senescence of chondrocytes and cartilage degeneration during OA
progression. Recent studies have shown that adipose-derived mesenchymal stem
cells exert paracrine effects protecting against degenerative changes in
chondrocytes. We have investigated whether the conditioned medium (CM) from
adipose-derived mesenchymal stem cells may regulate senescence features induced
by inflammatory stress in OA chondrocytes. Our results indicate that CM down
regulated senescence markers induced by interleukin-1beta including senescence
associated beta-galactosidase activity, accumulation of gammaH2AX foci and
morphological changes with enhanced formation of actin stress fibers. Treatment
of chondrocytes with CM also decreased the production of oxidative stress, the
activation of mitogen-activated protein kinases, and the expression of caveolin-1
and p21. The effects of CM were related to the reduction in p53 acetylation which
would be dependent on the enhancement of Sirtuin 1 expression. Therefore, CM may
exert protective effects in degenerative joint conditions by countering the
premature senescence of OA chondrocytes induced by inflammatory stress.
PMID- 27490264
TI - Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent - A
Systematic Literature Review.
AB - BACKGROUND: As Bangladesh, India and Nepal progress towards visceral
leishmaniasis (VL) elimination, it is important to understand the role of
asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar
dermal leishmaniasis (PKDL) in transmission. METHODOLOGY/ PRINCIPAL FINDING: We
reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple
databases to include studies on burden, risk factors, biomarkers, natural
history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers,
98 were included covering the years 1942 through 2016. ALI, PKDL and relapse
studies lacked a reference standard and appropriate biomarker. The prevalence of
ALI was 4-17-fold that of VL. The risk of ALI was higher in VL case contacts.
Most infections remained asymptomatic or resolved spontaneously. The proportion
of ALI that progressed to VL disease within a year was 1.5-23%, and was higher
amongst those with high antibody titres. The natural history of PKDL showed
variability; 3.8-28.6% had no past history of VL treatment. The infectiveness of
PKDL was 32-53%. The risk of VL relapse was higher with HIV co-infection.
Modelling studies predicted a range of scenarios. One model predicted VL
elimination was unlikely in the long term with early diagnosis. Another model
estimated that ALI contributed to 82% of the overall transmission, VL to 10% and
PKDL to 8%. Another model predicted that VL cases were the main driver for
transmission. Different models predicted VL elimination if the sandfly density
was reduced by 67% by killing the sandfly or by 79% by reducing their breeding
sites, or with 4-6y of optimal IRS or 10y of sub-optimal IRS and only in low
endemic setting. CONCLUSION/ SIGNIFICANCE: There is a need for xenodiagnostic and
longitudinal studies to understand the potential of ALI and PKDL as reservoirs of
infection.
PMID- 27490267
TI - Aviation Emissions Impact Ambient Ultrafine Particle Concentrations in the
Greater Boston Area.
AB - Ultrafine particles are emitted at high rates by jet aircraft. To determine the
possible impacts of aviation activities on ambient ultrafine particle number
concentrations (PNCs), we analyzed PNCs measured from 3 months to 3.67 years at
three sites within 7.3 km of Logan International Airport (Boston, MA). At sites
4.0 and 7.3 km from the airport, average PNCs were 2- and 1.33-fold higher,
respectively, when winds were from the direction of the airport compared to other
directions, indicating that aviation impacts on PNC extend many kilometers
downwind of Logan airport. Furthermore, PNCs were positively correlated with
flight activity after taking meteorology, time of day and week, and traffic
volume into account. Also, when winds were from the direction of the airport,
PNCs increased with increasing wind speed, suggesting that buoyant aircraft
exhaust plumes were the likely source. Concentrations of other pollutants [CO,
black carbon (BC), NO, NO2, NOx, SO2, and fine particulate matter (PM2.5)]
decreased with increasing wind speed when winds were from the direction of the
airport, indicating a different dominant source (likely roadway traffic
emissions). Except for oxides of nitrogen, other pollutants were not correlated
with flight activity. Our findings point to the need for PNC exposure assessment
studies to take aircraft emissions into consideration, particularly in populated
areas near airports.
PMID- 27490268
TI - Extending rule-based methods to model molecular geometry and 3D model resolution.
AB - BACKGROUND: Computational modeling is an important tool for the study of complex
biochemical processes associated with cell signaling networks. However, it is
challenging to simulate processes that involve hundreds of large molecules due to
the high computational cost of such simulations. Rule-based modeling is a method
that can be used to simulate these processes with reasonably low computational
cost, but traditional rule-based modeling approaches do not include details of
molecular geometry. The incorporation of geometry into biochemical models can
more accurately capture details of these processes, and may lead to insights into
how geometry affects the products that form. Furthermore, geometric rule-based
modeling can be used to complement other computational methods that explicitly
represent molecular geometry in order to quantify binding site accessibility and
steric effects. RESULTS: We propose a novel implementation of rule-based modeling
that encodes details of molecular geometry into the rules and binding rates. We
demonstrate how rules are constructed according to the molecular curvature. We
then perform a study of antigen-antibody aggregation using our proposed method.
We simulate the binding of antibody complexes to binding regions of the shrimp
allergen Pen a 1 using a previously developed 3D rigid-body Monte Carlo
simulation, and we analyze the aggregate sizes. Then, using our novel approach,
we optimize a rule-based model according to the geometry of the Pen a 1 molecule
and the data from the Monte Carlo simulation. We use the distances between the
binding regions of Pen a 1 to optimize the rules and binding rates. We perform
this procedure for multiple conformations of Pen a 1 and analyze the impact of
conformation and resolution on the optimal rule-based model. CONCLUSIONS: We find
that the optimized rule-based models provide information about the average steric
hindrance between binding regions and the probability that antibodies will bind
to these regions. These optimized models quantify the variation in aggregate size
that results from differences in molecular geometry and from model resolution.
PMID- 27490270
TI - Enhancing the Bipolar Redox Cycling Efficiency of Plane-Recessed Microelectrode
Arrays by Adding a Chemically Irreversible Interferent.
AB - The individual electrochemical anodic responses of dopamine (DA), epinephrine
(EP), and pyrocatechol (CT) were investigated at arrays of recessed gold disk
microelectrodes arrays (MEAs) covered by a gold plane electrode and compared to
those of their binary mixture (CT and EP) when the top-plane electrode was
operated as a bipolar electrode or as a collector. The interferent species (EP)
displays a chemically irreversible wave over the same potential range as the
chemically reversible ones of DA or CT. As expected, in the generator-collector
(GC) mode, EP did not contribute to the redox cycling amplification that occurred
only for DA or CT. Conversely, in the bipolar mode, the presence of EP
drastically increased the bipolar redox cycling efficiency of DA and CT. This
evidenced that the chemically irreversible oxidation of EP at the anodic poles of
the top plane floating electrode provided additional electron fluxes that were
used to more efficiently reduce the oxidized DA or CT species at the cathodic
poles. This suggests an easy experimental strategy for enhancing the bipolar
efficiency of MEAs up to reach a performance identical to that achieved when the
same MEAs are operated in a GC mode.
PMID- 27490271
TI - Corrigendum to "A joint compressed-sensing and super-resolution approach for very
high-resolution diffusion imaging".
PMID- 27490272
TI - A Branch-and-Bound Approach for Tautomer Enumeration.
AB - Knowledge about tautomer forms of a structure is important since, e.g., a
property prediction for a molecule can yield to different results which depend on
the individual tautomer. Tautomers are isomers that can be transformed to each
other through chemical equilibrium reactions. In this paper the first exact
Branch-and-Bound (B&B) algorithm to calculate tautomer structures is proposed.
The algorithm is complete in the sense of tautomerism and generates all possible
tautomers of a structure according to the tautomer definition, it is initialized
with. To be efficient, the algorithm takes advantage of symmetric and formation
properties. Some restrictions are used to enable an early pruning of some
branches of the B&B tree. This is important, since a simple enumeration strategy
would lead to number of candidate tautomers that is exponentially increasing with
the number of hydrogen atoms and their attachment sites. The proposed
implementation of the B&B algorithm covers the majority of the prototropic
tautomer cases, but can be adapted to other kinds of tautomerism too.
Furthermore, a computer processable definition of tautomerism is given in the
form of the moving hydrogen atom problem.
PMID- 27490273
TI - Establishing Good Computer Modelling Practice (GCMP) in the Prediction of
Chemical Toxicity.
AB - This paper suggests guidelines for good computer modelling practice (GCMP) when
predicting chemical toxicity, with similar purposes to those for Good Laboratory
Practice (GLP). The purpose of GCMP is not to specify what should be delivered
with models or predictions but to set out what must be done to ensure that work
can be audited, on site, in a way analogous to the auditing of studies conforming
to GLP; it is intended to confirm that work has been done properly, as distinct
from providing advice on how to do it. Comments are made on the guidelines and
how they might be followed, based on practical experience with the implementation
of such a scheme in the development of knowledge-based and quantitative structure
activity relationship models. It is hoped that publication of this paper will
encourage wider discussion of the subject leading to adoption of measures to
ensure the trustworthiness of computer modelling work that is carried out in
connection with regulatory submissions.
PMID- 27490274
TI - Assessing Confidence in Predictions Using Veracity and Utility - A Case Study on
the Prediction of Mammalian Metabolism by Meteor Nexus.
AB - A previous paper1 described new metrics, veracity and utility, for assessing the
performance of toxicity prediction systems that report confidence in their
predictions. Assessing the performance of systems that predict mammalian
metabolism is complicated by the absence of comprehensive sets of negative
observations and predictions. This paper presents an approach to assessing the
performance of such systems using veracity and utility.
PMID- 27490275
TI - Virtually Designed Triclosan-Based Inhibitors of Enoyl-Acyl Carrier Protein
Reductase of Mycobacterium tuberculosis and of Plasmodium falciparum.
AB - We report here new chemical structures of predicted nanomolar triclosan-based
inhibitors (TCLs) of Mycobacterium tuberculosis enoyl-acyl carrier protein
reductase (InhA) virtually proposed by computer-assisted molecular design. 3D
models of InhA-TCL complexes were prepared by in situ modifications of the
reference crystal structure (PDB entry 1P45) for a training set of 15 TCLs with
known InhA inhibitory activities. A QSAR model was built leading to linear
correlation between the calculated free energies of complexation (DeltaDeltaGcom
) and experimental values IC50 (exp) : pIC50 =-0.0657*DeltaDeltaGcom +3.0502,
R(2) =0.96. In addition, ligand-based quantitative pharmacophore model (PH4) was
built from bound conformations of the training set compounds and confirmed the
correlation between molecular models and observed activities: pIC50 (exp=)
0.8929*pIC50 (pre) -0.441, R(2) =0.95. Structural information from both models
helped us to propose new TCL analogues. A virtual library of TCLs with known
predicted activities against enoyl-acyl carrier protein reductase of Plasmodium
falciparum (PfENR) was evaluated, revealing dual target TCLs. Moreover, analysis
of binding site interactions suggested enriching substitutions, which led to more
potent TCLs with predicted pIC50 (pre) as low as 7 nM. The computational
approach, which used both free energy estimated from molecular modeling and 3D
QSAR pharmacophore model, was helpful in virtually proposing the dual-targeted
drugs and provided valuable information for the design of novel potential
antituberculotic agents.
PMID- 27490276
TI - Towards Better BBB Passage Prediction Using an Extensive and Curated Data Set.
AB - In the present report, the challenging task of drug delivery across the blood
brain barrier (BBB) is addressed via a computational approach. The BBB passage
was modeled using classification and regression schemes on a novel extensive and
curated data set (the largest to the best of our knowledge) in terms of log BB.
Prior to the model development, steps of data analysis that comprise chemical
data curation, structural, cutoff and cluster analysis (CA) were conducted.
Linear Discriminant Analysis (LDA) and Multiple Linear Regression (MLR) were used
to fit classification and correlation functions. The best LDA-based model showed
overall accuracies over 85 % and 83 % for the training and test sets,
respectively. Also a MLR-based model with acceptable explanation of more than 69
% of the variance in the experimental log BB was developed. A brief and general
interpretation of proposed models allowed the estimation on how 'near' our
computational approach is to the factors that determine the passage of molecules
through the BBB. In a final effort some popular and powerful Machine Learning
methods were considered. Comparable or similar performance was observed respect
to the simpler linear techniques. Most of the compounds with anomalous behavior
were put aside into a set denoted as controversial set and discussion regarding
to these compounds is provided. Finally, our results were compared with
methodologies previously reported in the literature showing comparable to better
results. The results could represent useful tools available and reproducible by
all scientific community in the early stages of neuropharmaceutical drug
discovery/development projects.
PMID- 27490277
TI - Physicochemical Profiles of the Marketed Agrochemicals and Clues for Agrochemical
Lead Discovery and Screening Library Development.
AB - Combinatorial chemistry, high-throughput and virtual screening technologies have
been extensively used for discovering agrochemical leads from chemical libraries.
The knowledge of the physicochemical properties of the marketed agrochemicals is
useful for guiding the design and selection of such libraries. Since the earlier
profiling of marketed agrochemicals, the number and types of marketed
agrochemicals have significantly increased. Recent studies have shown the change
of some physicochemical properties of oral drugs with time. There is a need to
also profile the physicochemical properties of the marketed agrochemicals. In
this work, we analyzed the key physicochemical properties of 1751 marketed
agrochemicals in comparison with the previously-analyzed herbicides and
insecticides, 106 391 natural products and 57 548 diverse synthetic libraries
compounds. Our study revealed the distribution profiles and evolution trend of
different types of agrochemicals that in many respects are broadly similar to the
reported profiles for oral drugs, with the most marked difference being that
agrochemicals have a lower number of hydrogen bond donors. The derived
distribution patterns provided the rule of thumb guidelines for selecting
potential agrochemical leads and also provided clues for further improving the
libraries for agrochemical lead discovery.
PMID- 27490278
TI - Difficulties in Performing Mesalazine Enemas and Factors Related to
Discontinuation Among Patients With Ulcerative Colitis.
AB - Current first-line treatment of ulcerative colitis consists of a combination of
mesalazine enemas and oral mesalazine; however, many patients may discontinue
mesalazine enemas. In this single-center, cross-sectional study, 165 outpatients
with ulcerative colitis completed a self-administered questionnaire regarding the
frequency of mesalazine enemas, difficulties in performing these enemas, and
factors possibly associated with their discontinuation, as well as patient
clinical and demographic characteristics. Of 165 patients, 34 (20.6%)
discontinued mesalazine enemas because of a lack of efficacy. Five of the 13
items assessing difficulties were answered affirmatively by the majority of
patients. Discontinuation of enema application was associated with a perceived
lack of efficacy, four or more bowel movements per day, and lower scores on
measurement of the doctor-patient relationship. Application of mesalazine enemas
by patients with ulcerative colitis may be improved by discussions with peers and
healthcare professionals and by adjusting the frequency of application or the
time of starting the enema based on worsening of ulcerative colitis.
PMID- 27490279
TI - Laxative Use and Self-Reported Constipation in a Community-Dwelling Elderly
Population: A Community-Based Survey From Australia.
AB - The objectives of this study were to (1) determine the prevalence of laxative use
and self-reported constipation and (2) identify risk factors associated with
constipation in a community-dwelling elderly population. A retrospective cross
sectional survey using data from the Australian Longitudinal Study of Ageing was
used to explore laxative use and constipation in a cohort of community-dwelling
older persons. The prevalence of laxative use was 15% and the prevalence of self
reported constipation was 21%. Females were more likely to report constipation
and use laxatives. Of those using laxatives, men were more likely to have their
laxatives prescribed by a doctor whereas women were more likely to self-medicate.
Poor self-rated health and a higher need for assistance with activities of daily
living were identified as risk factors for constipation. Constipation is a common
condition affecting the community-dwelling elderly. There is a need to optimize
the management of constipation and use of laxatives in such populations.
PMID- 27490280
TI - Confined Water Determines Transport Properties of Guest Molecules in Narrow
Pores.
AB - We computed the transport of methane through 1 nm wide slit-shaped pores carved
out of solid substrates. Models for silica, magnesium oxide, and alumina were
used as solid substrates. The pores were filled with water. The results show that
the methane permeability through the hydrated pores is strongly dependent on the
solid substrate. Detailed analysis of the simulated systems reveals that local
properties of confined water, including its structure, and more importantly,
evolution of solvation free energy and hydrogen bond structure are responsible
for the pronounced differences observed. The simulations are extended to
multicomponent systems representative of natural gas, containing methane, ethane,
and H2S. The results show that all pores considered have high affinity for H2S,
moderate affinity for methane, and low affinity for ethane. The H2S/methane
transport selectivity through the hydrated alumina pore is comparable, or
superior, to that reported for existing commercial membranes. A multiscale
approach was then implemented to demonstrate that a Smoluchowski one-dimensional
model is able to reproduce the molecular-level results for short pores when
appropriate values for the local self-diffusion coefficients are used as input
parameters. We propose that the model can be extended to predict methane
transport through uniform hydrated pores of macroscopic length. When verified by
experiments, our simulation results could have important implications in
applications such as natural gas sweetening and predictions of methane migration
through hydraulically fractured shale formations.
PMID- 27490282
TI - Erratum: Vol. 65, No. 26.
AB - In the report, "Notes from The Field: Ebola Virus Disease Cluster - Northern
Sierra Leone, January 2016," the name of a member of The Interagency
Investigation Team was incorrect and should have read as follows: "Matthew
Cotten, PhD, Wellcome Trust Sanger Institute, United Kingdom."
PMID- 27490281
TI - Three-Dimension Hierarchical Al2O3 Nanosheets Wrapped LiMn2O4 with Enhanced
Cycling Stability as Cathode Material for Lithium Ion Batteries.
AB - A three dimensional (3D) Al2O3 coating layer was synthesized by a facile approach
including stripping and in situ self-assembly of gamma-AlOOH. The uniform flower
like Al2O3 nanosheets with high specific area largely sequesters acidic species
produced by side reaction between electrode and electrolyte. The inner coating
layer wrapping spinel LiMn2O4 effectively inhibits the dissolution of Mn by
suppressing directive contact with electrolyte to enhance cycling stability. The
rate performance is improved because of the better electrolyte storage of the
assembled hierarchical architecture of the 3D coating layer affording unimpeded
Li(+) diffusion from electrode to electrolyte. The electrochemical results reveal
the as-prepared coated LiMn2O4 sample with the amount of Al2O3 at 1 wt % exhibits
superior cycle stability under room temperature even at elevated temperature. The
initial specific discharge capacity is 128.5 mAh g(-1) at 0.1 C and retains 89.8%
of the initial capacity after 800 cycles at 1 C rate. When cycling at 55 degrees
C, the composite shows 93.6% capacity retention after 500 cycles. This facile
surface modification and effective structure of coating layer can be adopted to
enhance the cycling performance and thermal stability of other electrode
materials for which Al2O3 plays its role.
PMID- 27490283
TI - Correction: A narrow amide I vibrational band observed by sum frequency
generation spectroscopy reveals highly ordered structures of a biofilm protein at
the air/water interface.
AB - Correction for 'A narrow amide I vibrational band observed by sum frequency
generation spectroscopy reveals highly ordered structures of a biofilm protein at
the air/water interface' by Zhuguang Wang et al., Chem. Commun., 2016, 52, 2956
2959.
PMID- 27490284
TI - Origin of axonal proteins: Is the axon-schwann cell unit a functional syncytium?
AB - The structural homeostasis is challenging for neurons, whose axons extend up to
meters in large animals, and the axoplasmic mass reaches over a thousand times
that of the cell body. Thus, the protein demand may overcome the capacity of the
cell body to supply the right protein species, to the right place, in the right
time. In this context, a body of evidence indicates that glial cells support the
axonal maintenance and regenerative responses by diverse mechanisms of
intercellular communication. We showed recently that Schwann cells (SC) transfer
ribosomes to axons and also enhance regeneration by means of extracellular
vesicles known as exosomes that contain mRNAs, miRNAs and proteins. These
findings strongly suggest that the nucleus of the SC supports the machinery for
protein synthesis of the axon and participates in the specification of the
phenotype of the underlying axon. That the genetic programs of many nuclei
modulate the axoplasm on a local basis is akin to a syncytium but at variance
with it, the nuclei belong to satellite cells. We propose that the SC-axon unit
is a functional syncytium. This intercellular organization opens a novel
understanding of the nervous system and a new avenue of research into its
physiology and disorders (c) 2016 Wiley Periodicals, Inc.
PMID- 27490285
TI - Miniaturized fibre-top cantilevers on etched fibres.
AB - Fibre-top probes are self-aligned, all optical devices obtained by carving a
cantilever on top of a 125-MUm diameter single-mode optical fibre. In this paper,
we show that this design can be adapted to smaller fibres as well. We evaluated
the performance of a 20-MUm diameter probe in contact mode atomic force
microscopy (AFM) and that of a 50-MUm diameter probe in nanoindentation
measurements. AFM images proved to be accurate both in air and water, although
some distortion was observed because of the mechanical bending of the fibre
during scanning. Indentation curves resembled those obtained with larger devices.
The maximum indentation depth, however, is limited by the small dimensions of the
cantilever.
PMID- 27490286
TI - Remarkable points for discussing outcomes of urodynamic studies.
PMID- 27490287
TI - Physician Assistant Genomic Competencies.
AB - Genomic discoveries are increasingly being applied to the clinical care of
patients. All physician assistants (PAs) need to acquire competency in genomics
to provide the best possible care for patients within the scope of their
practice. In this article, we present an updated version of PA genomic
competencies and learning outcomes in a framework that is consistent with the
current medical education guidelines and the collaborative nature of PAs in
interprofessional health care teams.
PMID- 27490288
TI - Educational Needs Assessment Highlights Several Areas of Emphasis in Teaching
Evidence-Based Medicine Skills to Physician Assistant Students.
AB - PURPOSE: An assessment of educational needs is essential for curricular reform in
medical education. Using the conceptual framework of needs assessment, this study
aimed to determine which content should be emphasized in teaching evidence-based
medicine (EBM) skills to physician assistant (PA) students. METHODS: Key content
areas were identified from the published literature and objectives for previous
courses. A questionnaire-type needs assessment instrument was created and given
to a graduating class of PA students (n = 21) at the University of North Dakota.
The response format had two 5-option scales, one to assess current skill levels
and the other to assess ideal skill levels. Means for each category were
calculated, and a mean difference analysis was performed. RESULTS: An average
mean difference of 0.5 was noted in 3 domains (information retrieval skills,
writing skills, and overall gains), and a mean difference of 0.7 was noted in one
domain (statistical skills). Items with a mean difference of >= 0.7 were
identified for prioritization for curricular reform. Open-ended input from
respondents substantiated the need for greater emphasis on these content areas.
CONCLUSION: Several content areas related to EBM skills can be identified and
prioritized through a systematically conducted educational needs assessment. This
method can be used to identify discrepancies between the existing and ideal
states of affairs in PA education.
PMID- 27490289
TI - Beyond the Clinic: Physician Assistant Student Perspectives on Careers in
Physician Assistant Education.
AB - PURPOSE: Professional training programs for physician assistants (PAs) have been
rapidly expanding. The profession therefore needs to develop a sufficiently
robust teaching workforce. METHODS: This study surveyed current PA students from
all Physician Assistant Education Association member programs to ascertain their
level of interest in and understanding of careers in PA education, including
faculty and precepting roles. RESULTS: The study revealed that interest was
greatest in precepting roles. A higher level of education before attending a PA
program correlated with a higher interest in PA education roles, although an
education-related degree did not show a significant relationship with such roles.
CONCLUSION: These and other study findings are important to consider as the
profession continues to develop a pipeline to education careers for students and
clinicians.
PMID- 27490290
TI - What Do Physician Assistant Students Know About Nutrition? A Survey of Attitudes,
Self-Perceived Proficiency, and Knowledge During Three Stages of Physician
Assistant Education.
AB - PURPOSE: This study applied a cross-sectional design and analyzed the nutrition
knowledge and attitudes of physician assistant (PA) students during 3 stages of
PA education. METHODS: The PA students from the class of 2014, 2015, and 2016
attending a midwestern university were surveyed using Qualtrics. Descriptive
statistics and analysis of variance tests were performed to determine the
difference between the 3 cohorts on "previous nutrition knowledge," "attitudes,"
and "knowledge" subscores and total scores. A post hoc analysis was performed to
determine the differences between groups. RESULTS: A statistically significant
difference was found in the mean total score between classes, with the class of
2014 scoring 17 points higher on average than the class of 2016. CONCLUSION:
These results suggest that positive nutrition attitudes and knowledge among PA
students from this sample were lacking. This study suggests a possible need for
revision of nutrition education provided by PA programs.
PMID- 27490291
TI - Durability of Expanded Physician Assistant Training Positions Following the End
of Health Resources and Services Administration Expansion of Physician Assistant
Training Funding.
AB - PURPOSE: The purpose of this study was to assess the number of Health Resources
and Services Administration Expansion of Physician Assistant Training (EPAT)
funded physician assistant (PA) programs planning to maintain class size at
expanded levels after grant funds expire and to report proposed financing
methods. The 5-year EPAT grant expired in 2015, and the effect of this funding on
creating a durable expansion of PA training seats has not yet been investigated.
METHODS: The study used an anonymous, 9-question, Web-based survey sent to the
program directors at each of the PA programs that received EPAT funding. Data
were analyzed in Excel and using SAS statistical analysis software for both
simple percentages and for Fisher's exact test. RESULTS: The survey response rate
was 81.48%. Eighty-two percent of responding programs indicated that they planned
to maintain all expanded positions. Fourteen percent will revert to their
previous student class size, and 4% will maintain a portion of the expanded
positions. A majority of the 18 programs (66%) maintaining all EPAT seats will be
funded by tuition pass-through, and one program (6%) will increase tuition. There
was no statistical association between the program type and the decision to
maintain expanded positions (P = .820). CONCLUSIONS: This study demonstrates that
the one-time EPAT PA grant funding opportunity created a durable expansion in PA
training seats. Future research should focus on the effectiveness of the program
in increasing the number of graduates choosing to practice in primary care and
the durability of expansion several years after funding expiration.
PMID- 27490292
TI - Critical Appraisal of the Randomized Controlled Trial.
PMID- 27490293
TI - Reinventing the Hospital Handoff for Clinical Education.
PMID- 27490294
TI - Telemedicine and Clinical Rotations: Worth Investigating?
PMID- 27490295
TI - Burn Management in Orthopaedic Trauma: A Critical Analysis Review.
PMID- 27490296
TI - A Strategy for Successful Implementation of Bundled Payments in Orthopaedic
Surgery.
PMID- 27490297
TI - Reverse Shoulder Arthroplasty for the Treatment of Proximal Humeral Fractures.
PMID- 27490298
TI - Decision-Making in the Treatment of the Spastic Shoulder and Elbow: Tendon
Release Versus Tendon Lengthening.
PMID- 27490300
TI - Where do uncertainties reside within environmental risk assessments? Expert
opinion on uncertainty distributions for pesticide risks to surface water
organisms.
AB - A reliable characterisation of uncertainties can aid uncertainty identification
during environmental risk assessments (ERAs). However, typologies can be
implemented inconsistently, causing uncertainties to go unidentified. We present
an approach based on nine structured elicitations, in which subject-matter
experts, for pesticide risks to surface water organisms, validate and assess
three dimensions of uncertainty: its level (the severity of uncertainty, ranging
from determinism to ignorance); nature (whether the uncertainty is epistemic or
aleatory); and location (the data source or area in which the uncertainty
arises). Risk characterisation contains the highest median levels of uncertainty,
associated with estimating, aggregating and evaluating the magnitude of risks.
Regarding the locations in which uncertainty is manifest, data uncertainty is
dominant in problem formulation, exposure assessment and effects assessment. The
comprehensive description of uncertainty described will enable risk analysts to
prioritise the required phases, groups of tasks, or individual tasks within a
risk analysis according to the highest levels of uncertainty, the potential for
uncertainty to be reduced or quantified, or the types of location-based
uncertainty, thus aiding uncertainty prioritisation during environmental risk
assessments. In turn, it is expected to inform investment in uncertainty
reduction or targeted risk management action.
PMID- 27490299
TI - Collaboration and entanglement: An actor-network theory analysis of team-based
intraprofessional care for patients with advanced heart failure.
AB - Despite calls for more interprofessional and intraprofessional team-based
approaches in healthcare, we lack sufficient understanding of how this happens in
the context of patient care teams. This multi-perspective, team-based interview
study examined how medical teams negotiated collaborative tensions. From 2011 to
2013, 50 patients across five sites in three Canadian provinces were interviewed
about their care experiences and were asked to identify members of their health
care teams. Patient-identified team members were subsequently interviewed to form
50 "Team Sampling Units" (TSUs), consisting of 209 interviews with patients,
caregivers and healthcare providers. Results are gathered from a focused analysis
of 13 TSUs where intraprofessional collaborative tensions involved treating fluid
overload, or edema, a common HF symptom. Drawing on actor-network theory (ANT),
the analysis focused on intraprofessional collaboration between specialty care
teams in cardiology and nephrology. The study found that despite a shared
narrative of common purpose between cardiology teams and nephrology teams, fluid
management tools and techniques formed sites of collaborative tension. In
particular, care activities involved asynchronous clinical interpretations,
geographically distributed specialist care, fragmented forms of communication,
and uncertainty due to clinical complexity. Teams 'disentangled' fluid in order
to focus on its physiological function and mobilisation. Teams also used distinct
'framings' of fluid management that created perceived collaborative tensions.
This study advances collaborative entanglement as a conceptual framework for
understanding, teaching, and potentially ameliorating some of the tensions that
manifest during intraprofessional care for patients with complex, chronic
disease.
PMID- 27490302
TI - 500-fold enhancement of in situ (13)C liquid state NMR using gyrotron-driven
temperature-jump DNP.
AB - A 550-fold increase in the liquid state (13)C NMR signal of a 50MUL sample was
obtained by first hyperpolarizing the sample at 20K using a gyrotron (260GHz),
then, switching its frequency in order to apply 100W for 1.5s so as to melt the
sample, finally, turning off the gyrotron to acquire the (13)C NMR signal. The
sample stays in its NMR resonator, so the sequence can be repeated with rapid
cooling as the entire cryostat stays cold. DNP and thawing of the sample are
performed only by the switchable and tunable gyrotron without external devices.
Rapid transition from DNP to thawing in one second time scale was necessary
especially in order to enhance liquid (1)H NMR signal.
PMID- 27490303
TI - Effect of ionic interaction between a hyperpolarized magnetic resonance chemical
probe and a gadolinium contrast agent for the hyperpolarized lifetime after
dissolution.
AB - In hyperpolarization of (13)C-enriched magnetic resonance chemical probes in the
solid-state, a trace amount of gadolinium (Gd) contrast agent can be used to
maximize polarization of the (13)C nuclear spins. Here, we report systematic
measurement of the spin-lattice relaxation time (T1) and enhancement level of
(13)C-enriched chemical probes in the presence of various Gd contrast agents in
the liquid-state after dissolution. Using two different (13)C probes having
opposite electric charges at neutral pH, we clearly show the T1 of hyperpolarized
(13)C was barely affected by the use of a Gd complex that displays repulsive
interaction with the (13)C probe in solution, whilst T1 was drastically shortened
when there was ionic attraction between probe and complex.
PMID- 27490301
TI - Associations of gestational and early life exposures to ambient air pollution
with childhood atopic eczema in Shanghai, China.
AB - Whether ambient air pollution is associated with childhood atopic eczema is
controversial. In this paper, we selected 3358 preschool children who had not
altered residences since pregnancy from a cross-sectional study during 2011-2012
in Shanghai, China, and obtained parent-reported data regarding childhood atopic
eczema using an improved ISAAC questionnaire. We recorded daily concentrations of
SO2, NO2, and PM10 throughout the child's lifetime (2006-2012), and calculated
period-averaged concentrations for each district where the child lived to
represent the child's exposure levels of these pollutants during different
periods. In the multiple logistic regression analyses adjusted for potential
confounders as well as for the other pollutants in the same periods, childhood
atopic eczema was significantly associated with increments of NO2 in the
approximate interquartile range (20MUg/m3) during gestational period (adjusted
OR, 95% CI for eczema lifetime-ever: 1.80, 1.29-2.49; for eczema in the year
prior to the survey: 2.32, 1.57-3.43) and during the first year of life (2.00,
1.40-2.84; 2.16, 1.43-3.28). Exposure to elevated NO2 in the first two years,
three years and total lifetime, as well as exposure to mixtures containing NO2 in
each of these periods, were consistently associated with increased likelihood of
childhood eczema. The highest odds ratios were found between exposure to a
mixture of SO2 and NO2 during total lifetime (increment: 35MUg/m3) and childhood
eczema (adjusted OR, 95% CI: 2.80, 1.75-4.48; 3.50, 1.98-6.19). No significant
associations were found between childhood eczema and ambient SO2 and PM10
individually or in mixtures. This study indicates that gestational and lifetime
exposures to ambient NO2 are risk factors for atopic eczema in childhood.
Exposure to ambient SO2 and PM10 may enhance the effect of NO2 exposure on
childhood eczema.
PMID- 27490304
TI - Neural correlates of accelerated auditory processing in children engaged in music
training.
AB - Several studies comparing adult musicians and non-musicians have shown that music
training is associated with brain differences. It is unknown, however, whether
these differences result from lengthy musical training, from pre-existing
biological traits, or from social factors favoring musicality. As part of an
ongoing 5-year longitudinal study, we investigated the effects of a music
training program on the auditory development of children, over the course of two
years, beginning at age 6-7. The training was group-based and inspired by El
Sistema. We compared the children in the music group with two comparison groups
of children of the same socio-economic background, one involved in sports
training, another not involved in any systematic training. Prior to
participating, children who began training in music did not differ from those in
the comparison groups in any of the assessed measures. After two years, we now
observe that children in the music group, but not in the two comparison groups,
show an enhanced ability to detect changes in tonal environment and an
accelerated maturity of auditory processing as measured by cortical auditory
evoked potentials to musical notes. Our results suggest that music training may
result in stimulus specific brain changes in school aged children.
PMID- 27490305
TI - Predictors of 30-day perioperative morbidity and mortality of unruptured
intracranial aneurysm surgery.
AB - INTRODUCTION: Large-scale studies examining the incidence and predictors of
perioperative complications after surgical clipping of unruptured intracranial
aneurysms (UIA) using nationally representative prospectively collected data are
lacking in the literature. METHODS: Using the American College of Surgeons'
National Surgical Quality Improvement Program (ACS-NSQIP) dataset, we conducted a
retrospective analysis of the complications experienced by patients that
underwent surgical management of a UIA between the years of 2007 and 2013. The
primary outcomes of interest were mortality within the 30-day perioperative
period and adverse discharge disposition to a location other than home.
Predictors of morbidity and mortality were elucidated using multivariable
logistic regression analyses controlling for available patient demographic,
comorbidity, and operative characteristics. RESULTS: 662 patients were identified
in the ACS-NSQIP dataset for operative management of an unruptured aneurysm. The
observed rates of 30-day mortality and adverse discharge disposition were 2.27%
and 19.47%, respectively. A hundred and eight (16.31%) patients developed at
least one major complication. On multivariable analysis, death within 30days was
significantly associated with increased operative time (OR 1.005 per minute, 95%
CI 1.002-1.008) and chronic preoperative corticosteroid use (OR 28.4, 95% CI 1.68
480.42), whereas major complication development was associated with increased
operative time (OR 1.004 per minute, 95% CI 1.002-1.006), age (OR 1.017 per year,
95% CI 1-1.034), preoperative dependency (OR 3.3, 95% CI 1.16-9.40) and diabetes
mellitus (OR 2.89, 95% CI 1.45-5.75). Lastly, increasing age (OR 1.017 per year,
95% CI 1-1.034) as well as ASA Class 3 (OR 1.73, 95% CI 1.08-2.77) and 4 (OR
2.28, 95% CI 1.1-4.72) were independent predictors of discharge to a location
other than home. CONCLUSION: Our study yields morbidity and mortality benchmarks
for UIA surgery in a representative, national surgical registry. It will
hopefully aid in recognizing those patients at greater risk for postoperative
complications following surgical management, leading to appropriate changes in
treatment strategies for this selected group of patients.
PMID- 27490306
TI - Interactions of gut microbiota with dietary polyphenols and consequences to human
health.
AB - PURPOSE OF REVIEW: Dietary (poly)phenolic compounds have received attention over
the last 20 years as antioxidants with preventive properties against chronic
diseases. However, the evidence of these effects in clinical trials is weak,
mainly because of a considerable interindividual variability. Polyphenols
bioavailability is low, and gut microbiota metabolize them into simpler
metabolites. As gut microbiota vary among individuals, such interindividual
variability should be considered as a moderating factor in clinical trials. In
this review, we show evidence of interactions with gut microbiota that help
understanding polyphenols' health effects. RECENT FINDINGS: Recent studies
indicate that dietary polyphenols are relevant in the modulation of gut
microbiota and that these microorganisms convert polyphenols into active and
bioavailable metabolites; hence, variations in gut microbiota can affect
polyphenol activity. SUMMARY: The results show that study participants'
stratification by their polyphenol-metabolizing phenotypes would be necessary for
clinical trials as specific metabotypes produce the bioactive metabolites
responsible for the health effects. Metabotypes can also reflect the gut
microbiota composition and metabolic status, and could be biomarkers of the
potential polyphenol health effects mediated through gut microbiota.
PMID- 27490307
TI - Similarities in the Retinal Appearance of Patients With Zika Virus Compared With
Cobalamin C Deficiency.
PMID- 27490309
TI - TiCl4-Mediated Preparation of Thiophthalide Derivatives via Formal Thio-Passerini
Reactions.
AB - By the formal extension of the Passerini reaction to thiocarbonyl derivatives,
the straightforward preparation of thiophthalides is disclosed. This method
involves the intermediate formation of a sulfanyl-phthalide and a titanium
tetrachloride mediated isocyanide insertion reaction. When tert-butyl thiol is
used, thanks to the deprotection of the tert-butyl group, a thiophthalide
resulting from a 1,5-Mumm rearrangement is isolated. Owing to the multifaceted
activity of TiCl4, all steps may conveniently be performed in one pot, starting
directly from 2-formylbenzoic acids, tert-butyl thiol, and various isocyanides.
PMID- 27490310
TI - Association of Intraoperative Neuromonitoring With Reduced Recurrent Laryngeal
Nerve Injury in Patients Undergoing Total Thyroidectomy.
AB - Importance: Injury of the recurrent laryngeal nerve (RLN) is one of the most
serious complications of thyroid surgery. Intraoperative neuromonitoring (IONM)
has been introduced to verify RLN function integrity and may be a helpful adjunct
in nerve dissection. Objective: To determine whether the use of IONM can reduce
the incidence of RLN injury in patients undergoing total thyroidectomy. Design,
Setting, and Participants: This cohort study included 2556 patients who underwent
total thyroidectomy between January 2002 and December 2012 in the Department of
Otolaryngology-Head and Neck Surgery of Venizeleio General Hospital, Heraklion,
Greece. Patients who had IONM during the procedure (n = 1481) were compared with
patients who underwent surgery with nerve visualization alone (n = 1075). All
patients underwent indirect laryngoscopy-fiberoptic nasopharyngoscopy both
preoperatively and on day 2 after surgery to assess vocal cord motility. Main
Outcomes and Measures: Use of IONM and incidence of RLN injury. Results: A total
of 2556 patients (2028 women and 528 men [5112 RLNs at risk]; mean [SD] age,
51.35 [14.18] years; age range, 18-89 years) underwent total thyroidectomy.
Univariate analysis showed that the use of IONM resulted in a significant
reduction in RLN injury incidence (3.3% vs 0.7%) with a relative risk reduction
of 2.6% (odds ratio [OR], 5.15; 95% CI, 3.12-8.49; number needed to treat, 19).
Multivariate logistic regression showed that no use of IONM was an independent
risk factor for RLN injury in patients who underwent total thyroidectomy
(adjusted OR [AOR], 5.44; 95% CI, 3.26-9.09). Additional risk factors for RLN
injury were operative time (AOR, 12.91; 95% CI, 6.66-25.06), maximum diameter
greater than 45 mm of right thyroid lobe (AOR, 4.91; 95% CI, 3.12-8.56) and left
thyroid lobe (AOR, 2.24; 95% CI, 1.39-4.32), extrathyroid extension (AOR, 3.26;
95% CI, 1.62-6.59), incidental parathyroidectomy (AOR, 3.30; 95% CI, 2.13-5.09),
and tumor size larger than 10 mm (AOR, 3.24; 95% CI, 1.59-6.62). Conclusions and
Relevance: Our findings showed that the use of IONM decreased significantly both
temporary and permanent RLN injuries. The technology of IONM is safe and
reliable, and this technique is an important adjunct in nerve dissection and
functional neural integrity. The routine use of IONM reduced pitfalls and
provided guidance for our surgeons in difficult cases, reoperations, and high
risk patients.
PMID- 27490308
TI - Effects of Visible-Light Irradiation of Protoporphyrin IX on the Self-Assembly of
Tubulin Heterodimers.
AB - The formation and the effects of laser irradiation of the complex formed by
protoporphyrin IX (PPIX) and tubulin was investigated. We have used tubulin as a
model protein to investigate whether docked photoactive ligands can affect the
structure and function of polypeptides upon exposure to visible light. We
observed that laser irradiation in the Soret band prompts bleaching of the PPIX,
which is accompanied by a sharp decrease in the intensity and average
fluorescence lifetime of the protein (dominated by the four tryptophan residues
of the tubulin monomer). The kinetics indicate non-trivial effects and suggest
that the photosensitization of the PPIX bound to tubulin prompts structural
alterations of the protein. These modifications were also observed through
changes in the energy transfer between Trp residues and PPIX. The results suggest
that laser irradiation produces localized partial unfolding of tubulin and that
the changes prompt modification of the formation of microtubules in vitro.
Measurements of singlet oxygen formation were inconclusive in determining whether
the changes are prompted by reactive oxygen species or other excited state
mechanisms.
PMID- 27490311
TI - The Hydroxysteroid (17beta) Dehydrogenase Family Gene HSD17B12 Is Involved in the
Prostaglandin Synthesis Pathway, the Ovarian Function, and Regulation of
Fertility.
AB - The hydroxysteroid (17beta) dehydrogenase (HSD17B)12 gene belongs to the
hydroxysteroid (17beta) dehydrogenase superfamily, and it has been implicated in
the conversion of estrone to estradiol as well as in the synthesis of arachidonic
acid (AA). AA is a precursor of prostaglandins, which are involved in the
regulation of female reproduction, prompting us to study the role of HSD17B12
enzyme in the ovarian function. We found a broad expression of HSD17B12 enzyme in
both human and mouse ovaries. The enzyme was localized in the theca interna,
corpus luteum, granulosa cells, oocytes, and surface epithelium. Interestingly,
haploinsufficiency of the HSD17B12 gene in female mice resulted in subfertility,
indicating an important role for HSD17B12 enzyme in the ovarian function. In line
with significantly increased length of the diestrous phase, the HSD17B+/- females
gave birth less frequently than wild-type females, and the litter size of
HSD17B12+/- females was significantly reduced. Interestingly, we observed meiotic
spindle formation in immature follicles, suggesting defective meiotic arrest in
HSD17B12+/- ovaries. The finding was further supported by transcriptome analysis
showing differential expression of several genes related to the meiosis. In
addition, polyovular follicles and oocytes trapped inside the corpus luteum were
observed, indicating a failure in the oogenesis and ovulation, respectively.
Intraovarian concentrations of steroid hormones were normal in HSD17B12+/-
females, whereas the levels of AA and its metabolites (6-keto prostaglandin
F1alpha, prostaglandin D2, prostaglandin E2, prostaglandin F2alpha, and
thromboxane B2) were decreased. In conclusion, our study demonstrates that
HSD17B12 enzyme plays an important role in female fertility through its role in
AA metabolism.
PMID- 27490312
TI - Empathic Communication in Virtual Education for Nursing Students: I'm Sorry to
Hear That.
AB - The current study examined the communication strategies used by undergraduate
nursing students (N = 343) to express empathy during simulated health history
interviews. Interacting with a virtual patient, students encountered up to 9
information disclosures that warranted the expression of empathy but recognized
few (33.54%). Sophistication of language to express empathy varied depending on
the disclosure topic. These findings suggest that empathy as a learned skill can
be incorporated into a variety of nursing contexts.
PMID- 27490313
TI - Content Validation of a Quality and Safety Education for Nurses-Based Clinical
Evaluation Instrument.
AB - Quality and Safety Education for Nurses (QSEN) has been prominent in nursing
education for 10 years. Since its inception, faculty have used the QSEN
competencies as a framework for developing teaching strategies and tools, but
there are few findings available to support this practice. This article describes
the process of developing a QSEN-based clinical evaluation instrument for a
prelicensure nursing program and establishing content validation for its items
using the content validity index.
PMID- 27490314
TI - Effective Learning of Interprofessional Teamwork.
AB - Educators are actively identifying optimal teaching-learning strategies that
afford future health care professionals opportunities to acquire skills necessary
to function as a member of an interprofessional team. This article describes the
development of an interprofessional team learning experience consisting of
students from 6 health professions programs within 1 college of health
professions. Student achievement of interprofessional team competencies were
evaluated in a pretest-posttest format. Essential components of a 7-week program,
teaching methodologies, and course evaluations are presented.
PMID- 27490315
TI - Penalized weighted least-squares approach for multienergy computed tomography
image reconstruction via structure tensor total variation regularization.
AB - Multienergy computed tomography (MECT) allows identifying and differentiating
different materials through simultaneous capture of multiple sets of energy
selective data belonging to specific energy windows. However, because sufficient
photon counts are not available in each energy window compared with that in the
whole energy window, the MECT images reconstructed by the analytical approach
often suffer from poor signal-to-noise and strong streak artifacts. To address
the particular challenge, this work presents a penalized weighted least-squares
(PWLS) scheme by incorporating the new concept of structure tensor total
variation (STV) regularization, which is henceforth referred to as 'PWLS-STV' for
simplicity. Specifically, the STV regularization is derived by penalizing higher
order derivatives of the desired MECT images. Thus it could provide more robust
measures of image variation, which can eliminate the patchy artifacts often
observed in total variation (TV) regularization. Subsequently, an alternating
optimization algorithm was adopted to minimize the objective function. Extensive
experiments with a digital XCAT phantom and meat specimen clearly demonstrate
that the present PWLS-STV algorithm can achieve more gains than the existing TV
based algorithms and the conventional filtered backpeojection (FBP) algorithm in
terms of both quantitative and visual quality evaluations.
PMID- 27490316
TI - Surface reconstruction for planning and navigation of liver resections.
AB - Computer-assisted systems for planning and navigation of liver resection
procedures rely on the use of patient-specific 3D geometric models obtained from
computed tomography. In this work, we propose the application of Poisson surface
reconstruction (PSR) to obtain 3D models of the liver surface with applications
to planning and navigation of liver surgery. In order to apply PSR, the
introduction of an efficient transformation of the segmentation data, based on
computation of gradient fields, is proposed. One of the advantages of PSR is that
it requires only one control parameter, allowing the process to be fully
automatic once the optimal value is estimated. Validation of our results is
performed via comparison with 3D models obtained by state-of-art Marching Cubes
incorporating Laplacian smoothing and decimation (MCSD). Our results show that
PSR provides smooth liver models with better accuracy/complexity trade-off than
those obtained by MCSD. After estimating the optimal parameter, automatic
reconstruction of liver surfaces using PSR is achieved keeping similar processing
time as MCSD. Models from this automatic approach show an average reduction of
79.59% of the polygons compared to the MCSD models presenting similar smoothness
properties. Concerning visual quality, on one hand, and despite this reduction in
polygons, clinicians perceive the quality of automatic PSR models to be the same
as complex MCSD models. On the other hand, clinicians perceive a significant
improvement on visual quality for automatic PSR models compared to optimal
(obtained in terms of accuracy/complexity) MCSD models. The median reconstruction
error using automatic PSR was as low as 1.03+/-0.23mm, which makes the method
suitable for clinical applications. Automatic PSR is currently employed at Oslo
University Hospital to obtain patient-specific liver models in selected patients
undergoing laparoscopic liver resection.
PMID- 27490317
TI - Watertight modeling and segmentation of bifurcated Coronary arteries for blood
flow simulation using CT imaging.
AB - Image-based simulation of blood flow using computational fluid dynamics has been
shown to play an important role in the diagnosis of ischemic coronary artery
disease. Accurate extraction of complex coronary artery structures in a
watertight geometry is a prerequisite, but manual segmentation is both tedious
and subjective. Several semi- and fully automated coronary artery extraction
approaches have been developed but have faced several challenges. Conventional
voxel-based methods allow for watertight segmentation but are slow and difficult
to incorporate expert knowledge. Machine learning based methods are relatively
fast and capture rich information embedded in manual annotations. Although
sufficient for visualization and analysis of coronary anatomy, these methods
cannot be used directly for blood flow simulation if the coronary vasculature is
represented as a loose combination of tubular structures and the bifurcation
geometry is improperly modeled. In this paper, we propose a novel method to
extract branching coronary arteries from CT imaging with a focus on explicit
bifurcation modeling and application of machine learning. A bifurcation lumen is
firstly modeled by generating the convex hull to join tubular vessel branches.
Guided by the pre-determined centerline, machine learning based segmentation is
performed to adapt the bifurcation lumen model to target vessel boundaries and
smoothed by subdivision surfaces. Our experiments show the constructed coronary
artery geometry from CT imaging is accurate by comparing results against the
manually annotated ground-truths, and can be directly applied to coronary blood
flow simulation.
PMID- 27490318
TI - Connexin43 Mimetic Peptide Improves Retinal Function and Reduces Inflammation in
a Light-Damaged Albino Rat Model.
AB - PURPOSE: Drugs that regulate connexin43 (Cx43) gap junction channels can reduce
the spread of injury and improve functional outcomes after nervous system trauma.
In the eye, Cx43 expression increases in the choroid following light damage. The
aim of this study was to investigate whether Cx43 hemichannel block could
preserve retinal function postinjury. METHODS: Light damage was induced by
exposure of adult albino Sprague-Dawley rats to 2700 Lux light for 24 hours.
Intravitreal injections of a Cx43 mimetic peptide hemichannel blocker, Peptide5,
or sham were administered 2 hours after the onset and at the end of the light
damage period. Retinal function was assessed by electroretinogram and
inflammatory responses in the choroid and retina were assessed using
immunohistochemistry (ionized calcium binding adaptor molecule 1 [Iba-1],
leukocyte common antigen [CD45], glial fibrillary acidic protein [GFAP]).
RESULTS: Light-damaged rat eyes had (1) reduced neuronal responses in both the
rod and cone pathways and (2) marked inflammatory responses in the choroid and
retina. Peptide5 significantly preserved function of photoreceptoral and
postphotoreceptoral neurons in these animals. This was evident 24 hours after
injury and 2 weeks later, as shown by improved mixed a-wave and mixed b-wave
amplitudes, isolated rod PII and PIII amplitudes, and cone PII responses when
compared with sham-treated controls. Retinal thinning and inflammation were also
significantly reduced in Peptide5-treated eyes when compared with sham-treated
controls. CONCLUSIONS: Blocking Cx43 hemichannels after light damage can
significantly improve functional outcomes of neurons in both the rod and cone
photo-transduction pathways in the light-damaged animal model, likely by reducing
choroid inflammation and suppressing the glial-mediated inflammatory response.
These data may have relevance for the treatment of conditions such as diabetic
retinopathy and age-related macular degeneration.
PMID- 27490319
TI - Functional and Morphologic Changes of Meibomian Glands in an Asymptomatic Adult
Population.
AB - PURPOSE: The aim of the study was to understand natural changes of meibomian
glands (MG) that occur with aging in the absence of any ocular pathology or
ocular discomfort symptoms, to differentiate between "age normal" and pathologic
or dysfunctional changes of the MG. METHODS: A total of 185 subjects (109
females) with no pre-existing ocular and systemic abnormalities were recruited
and divided into four age groups: 25 to 34, 35 to 44, 45 to 54, and 55 to 66
years. At a single visit, the following MG measures were collected: meibum
quality (MQ) and MG expressibility (MGE) of the lower lid, and MG drop-out score
(meiboscale) using infrared meibography of the upper and lower lids. Assessments
of anterior eye, tear function variables, noninvasive and invasive tear breakup
time (TBUT), corneal integrity, and lid wiper epitheliopathy were also performed
during the visit. An Ocular Surface Disease Index (OSDI) questionnaire was used
to record dry eye symptoms. Meibum lipids samples were collected and analyzed.
RESULTS: A majority of the study population (61%) was asymptomatic. There was a
significant worsening in the MQ (P< 0.048), MGE (P < 0.03), and meiboscale (P <
0.01) with increasing age. Significant increase was observed in anterior
blepharitis (P < 0.001) and telangiectasia (P< 0.02) with aging. Interestingly,
tear osmolarity decreased significantly (P < 0.001), while tear meniscus height
(P < 0.001) and invasive TBUT (P = 0.02) increased with increase in age. There
was no significant association between MG variables and sex, ocular discomfort
symptoms, or meibum lipids classes. CONCLUSIONS: Progressive MG loss occurs
normally with age accompanied by reduced quality and quantity of the meibum
produced. However, clinical presentation of ocular discomfort symptoms is stalled
without corresponding disruption to tear function.
PMID- 27490320
TI - Characteristics of Retinal Nerve Fiber Layer Defect in Nonglaucomatous Eyes With
Type II Diabetes.
AB - PURPOSE: To investigate the characteristics of retinal nerve fiber layer (RNFL)
defects associated with type II diabetes. METHODS: Forty nonglaucomatous eyes
with type II diabetes and 54 eyes with early open angle glaucoma that exhibited a
localized RNFL defect and 42 eyes from age- and sex-matched nondiabetic,
nonglaucomatous controls were imaged with red-free fundus photography and optical
coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec). The area under the
receiver operating characteristic curves of eyes with diabetes was compared with
that of eyes with glaucoma. When an RNFL defect on fundus photographs was
identified in the quadrant, clock-hour, temporal-superior-nasal-inferior-temporal
(TSNIT), deviation, and thickness maps, it was considered a true detection.
RESULTS: In eyes with diabetes, the RNFL defects were located more frequently in
the superior hemisphere than they were in those with glaucoma (P < 0.001). The
angular locations of RNFL defects in eyes with diabetes (56.1 +/- 12.7 degrees )
were significantly farther from the fovea compared with those in glaucoma (44.3
+/- 17.3 degrees ; P < 0.001); in addition, the width of RNFL defects in diabetes
(5.1 +/- 2.3 degrees ) was significantly narrower than those in glaucoma (20.8 +/
12.3 degrees ; P < 0.001). The best parameter discriminating RNFL defects in
diabetes from those in glaucoma was width of RNFL defect (0.955), followed by rim
area (0.844), and average RNFL (0.791). The thickness map showed a sensitivity
(70%) and specificity (69.1%), superior to those of all other maps in eyes with
diabetes. CONCLUSIONS: The narrow width and identification of RNFL defect in
thickness map obtained with Cirrus HD-OCT seems to be an effective tool for
detecting RNFL defects in diabetes.
PMID- 27490321
TI - Erratum.
PMID- 27490322
TI - Phase Synchronization Analysis of Natural Wake and Sleep States in Healthy
Individuals Using a Novel Ensemble Phase Synchronization Measure.
AB - PURPOSE: Electrical activity in the brain is presumed to arise from a combination
of tonic asynchronous neuronal firing during wake and a synchronized, burst-pause
firing of large number of neurons during sleep. This study aims to compare the
phase synchronization index (SI) across multiple channels during wake and various
sleep stages on scalp electroencephalographic recordings. METHODS: Forty healthy
subjects were subjected to overnight polysomnography using 8-channel
electroencephalography. Electroencephalographic phase synchronization during
awake, non-rapid eye movement (N1, N2, N3), and rapid eye movement sleep states
was studied using ensemble measure (multichannel measure across all the eight
channels based on Hilbert transformation between any two pairs). RESULTS: With
the progression of states of wakefulness to non-rapid eye movement sleep, there
was progressive increase in phase SI in delta band while SI decreased in alpha
band (P < 0.001). The SI in delta band during rapid eye movement was comparable
with that of awake state (P < 0.001). In theta band, SI tends to decrease in N2
and increase in N3 (P < 0.001). In beta band, there was progressive increase in
SI from awake to non-rapid eye movement stages that decreased in rapid eye
movement stage (P < 0.001). CONCLUSIONS: This is the first study that has used an
ensemble measure to assess the long-range cortical phase synchronization during
awake and various sleep stages. The findings support the previous view of
increased delta synchrony during non-rapid eye movement sleep and alpha synchrony
during wakefulness. Rapid eye movement stage was characterized by marked
desynchrony in all frequency bands. These findings suggest the possible role of
cortical synchronization in influencing the occurrence of epileptic activity
during sleep and awake states.
PMID- 27490323
TI - Maximizing the Yield of Rapid Eye Movement Sleep in the Epilepsy Monitoring Unit.
AB - PURPOSE: Rapid eye movement (REM) sleep can help localize the epileptogenic zone
in multifocal epilepsy when interictal discharges appear diffuse. However, REM
sleep is reputedly rare and easily overlooked in the Epilepsy Monitoring Unit
(EMU). The aims of this study are to determine the characteristics of REM sleep
in a typical EMU and whether using automated artifact recognition can
meaningfully enhance REM sleep detection. METHODS: Artifact-based REM sleep
detection was applied to 581 nights of EMU recording from 100 patients over 12
months. REM sleep had been manually detected at the time of recording. The index
of suspicion for manual detection was raised after 6 months. Artifact-based
detection was compared with manual detection, and the impact on localization was
assessed. RESULTS: REM sleep occurred in 77% of EMU nights. Thirty-six patients
achieved REM sleep nightly and 62 patients on at least one night. Mean admission
was 5.83 days. Mean REM sleep duration was 5.92 minutes over 1.88 mean nightly
bouts. Raising the level of suspicion increased manual detection rates from 22.6%
to 40.5%. The artifact-based detection rate was 96% and provided additional
localizing information in 10% of epilepsy patients. CONCLUSIONS: REM sleep is
common in the EMU, but bouts are few and brief. Capturing these bouts to maximize
the yield of REM sleep in the EMU is made possible by automated artifact
recognition whose results could enhance localization of the epileptogenic zone.
PMID- 27490324
TI - Large Amplitude Cortical Evoked Potentials in Nonepileptic Patients. Reviving an
Old Neurophysiologic Tool to Help Detect CNS Pathology.
AB - PURPOSE: Although large amplitude evoked potentials (EPs) are typically
associated with progressive myoclonic epilepsy patients, giant EPs imply central
nervous system (CNS) hyperexcitability and can be seen in various nonepileptic
disorders. METHODS: We performed a retrospective chart review including history,
physical examination, imaging and diagnostic studies of nonepileptic patients
with large amplitude somatosensory evoked potentials (SSEPs) and visual evoked
potentials (VEPs) during 2007 to 2013. Large amplitude EPs were defined as
follows: VEPs (N75-P100) >18 MUV; and SSEPs (N20-P25) >6.4 MUV. Recording montage
for VEPs was Oz-Cz and SSEPs C3'/C4'-Fz. RESULTS: Fifty-two patients (33 females,
19 males; age range, 9-90 years) were identified. No CNS pathology was detected
in 7 patients. All remaining patients were diagnosed with new CNS disorders
including: vascular (37%); myelopathies (13%); demyelinating (11%); space
occupying lesions (8.7%); syringomyelia (8.7%); hydrocephalus (6.5%); Vitamin B
12 deficiency (4.3%); multiple system atrophy (4.3%); and toxins (2.2%).
CONCLUSIONS: This study supports the notion that large amplitude EP implies CNS
hyperexcitability and CNS disease. These results confirm the utility of EP
studies in patients with suspected CNS pathology.
PMID- 27490325
TI - Hyperventilation in Patients With Focal Epilepsy: Electromagnetic Tomography,
Functional Connectivity and Graph Theory - A Possible Tool in Epilepsy Diagnosis?
AB - PURPOSE: Hyperventilation (HV) is a commonly used electroencephalogram activation
method. METHODS: We analyzed EEG recordings in 22 normal subjects and 22 patients
with focal epilepsy of unknown cause. We selected segments before (PRE), during
(HYPER), and 5 minutes after (POST) HV. To analyze the neural generators of EEG
signal, we used standard low-resolution electromagnetic tomography (sLORETA
software). We then computed EEG lagged coherence, an index of functional
connectivity, between 19 regions of interest. A weighted graph was built for each
band in every subject, and characteristic path length (L) and clustering
coefficient (C) have been computed. Statistical comparisons were performed by
means of analysis of variance (Group X Condition X Band) for mean lagged
coherence, L and C. RESULTS: Hyperventilation significantly increases EEG neural
generators (P < 0.001); the effect is particularly evident in cingulate cortex.
Functional connectivity was increased by HV in delta, theta, alpha, and beta
bands in the Epileptic group (P < 0.01) and only in theta band in Control group.
Intergroup analysis of mean lagged coherence, C and L, showed significant
differences for Group (P < 0.001), Condition (P < 0.001), and Band (P < 0.001).
Analysis of variance for L also showed significant interactions: Group X
Condition (P = 0.003) and Group X Band (P < 0.001). CONCLUSIONS: In our
relatively small group of epileptic patients, HV is associated with activation of
cingulate cortex; moreover, it modifies brain connectivity. The significant
differences in mean lagged coherence, path length, and clustering coefficient
permit to hypothesize that this activation method leads to different brain
connectivity patterns in patients with epilepsy when compared with normal
subjects. If confirmed by other studies involving larger populations, this
analysis could become a diagnostic tool in epilepsy.
PMID- 27490326
TI - Unilateral Mu Rhythm and Associated Cortical Lesions on Brain MRI.
AB - PURPOSE: The purpose of this study was to assess the frequency of occurrence of a
unilateral mu rhythm and the associated neuroimaging findings on dedicated
epilepsy protocol brain MRI. METHODS: We retrospectively reviewed the EEG reports
database at the American University of Beirut Medical Center between 2011 and
2014 searching for the presence of a unilateral mu rhythm. For patients with a
unilateral mu rhythm, we recorded the patients' demographics, number of EEGs
performed, characteristics of the mu activity, and the findings on the epilepsy
protocol brain MRIs. RESULTS: A total of 7986 patients underwent 9,509 EEG
between 2011 and 2014. Four patients (0.05%) aged between 19 and 55 years had
evidence of a unilateral mu rhythm. Three patients were diagnosed with
localization-related epilepsy and one with syncope. The brain MRIs showed
cortical lesions involving the parietal cortex, ipsilateral to the unilateral mu
rhythm in the three patients with epilepsy. CONCLUSIONS: A unilateral mu rhythm
is a rare phenomenon on the scalp EEG that should prompt a search for an
ipsilateral lesion, even in the absence of additional EEG abnormalities.
PMID- 27490327
TI - Measuring the Severity of Neonatal Seizures: Temporal-Spatial Burden.
AB - PURPOSE: The American Clinical Neurophysiology Society recommends measuring
neonatal seizures' severity by their frequency (number of seizures-anywhere per
hour), burden (percentage of time with seizures-anywhere), or on a region-by
region, temporal-spatial basis. This study compares two reduced-channel montages
for temporal-spatial seizure burden analyses and examines the agreement of
seizures' quantification among these three methodologies. METHODS: A convenience
sample of 10 neonatal electroencephalograms was annotated for the beginnings and
ends of seizures, which appeared anywhere in the full neonatal montage, then
repeated on a more precise, region-by-region basis using 2 reduced-channel
montages A and B. Seizure severity was measured by seizures-anywhere frequency,
seizures-anywhere burden, and temporal-spatial seizure burdens using montages A
and B. The results were compared by measuring their correlation and by linear
regression modeling. RESULTS: Seizures-anywhere frequency was correlated with
seizures-anywhere burden (rho = 0.77). However, a narrow range of seizures
anywhere frequencies corresponded with a broad range of seizures-anywhere
burdens. Although there was high correlation between seizures-anywhere burdens
and temporal-spatial seizure burdens (rho = 0.92 montage A, rho = 0.90 montage
B), seizures-anywhere burdens were insensitive to variations in the spatial
aspects of seizures, which were highly prevalent even in this small sample set.
After adjusting for intrareader variability, the temporal-spatial seizure burdens
measured by montages A and B were not significantly different (P = 0.56).
CONCLUSIONS: The severity of neonatal seizures is poorly represented by simple
measures such as seizures-anywhere frequencies or burdens. The use of temporal
spatial seizure burden measurements is supported in work where great precision in
quantifying neonatal seizures is required.
PMID- 27490328
TI - The effectiveness of a nurse practitioner-led pain management team in long-term
care: A mixed methods study.
AB - BACKGROUND: Considering the high rates of pain as well as its under-management in
long-term care (LTC) settings, research is needed to explore innovations in pain
management that take into account limited resource realities. It has been
suggested that nurse practitioners, working within an inter-professional model,
could potentially address the under-management of pain in LTC. OBJECTIVES: This
study evaluated the effectiveness of implementing a nurse practitioner-led, inter
professional pain management team in LTC in improving (a) pain-related resident
outcomes; (b) clinical practice behaviours (e.g., documentation of pain
assessments, use of non-pharmacological and pharmacological interventions); and,
(c) quality of pain medication prescribing practices. METHODS: A mixed method
design was used to evaluate a nurse practitioner-led pain management team,
including both a quantitative and qualitative component. Using a controlled
before-after study, six LTC homes were allocated to one of three groups: 1) a
nurse practitioner-led pain team (full intervention); 2) nurse practitioner but
no pain management team (partial intervention); or, 3) no nurse practitioner, no
pain management team (control group). In total, 345 LTC residents were recruited
to participate in the study; 139 residents for the full intervention group, 108
for the partial intervention group, and 98 residents for the control group. Data
was collected in Canada from 2010 to 2012. RESULTS: Implementing a nurse
practitioner-led pain team in LTC significantly reduced residents' pain and
improved functional status compared to usual care without access to a nurse
practitioner. Positive changes in clinical practice behaviours (e.g., assessing
pain, developing care plans related to pain management, documenting effectiveness
of pain interventions) occurred over the intervention period for both the nurse
practitioner-led pain team and nurse practitioner-only groups; these changes did
not occur to the same extent, if at all, in the control group. Qualitative
analysis highlighted the perceived benefits of LTC staff about having access to a
nurse practitioner and benefits of the pain team, along with barriers to managing
pain in LTC. CONCLUSIONS: The findings from this study showed that implementing a
nurse practitioner-led pain team can significantly improve resident pain and
functional status as well as clinical practice behaviours of LTC staff. LTC homes
should employ a nurse practitioner, ideally located onsite as opposed to an
offsite consultative role, to enhance inter-professional collaboration and
facilitate more consistent and timely access to pain management.
PMID- 27490329
TI - Metastasis to the Heart: A Radiologic Approach to Diagnosis With Pathologic
Correlation.
AB - OBJECTIVE: Evaluating metastatic disease to the heart and pericardium, from
detection to diagnosis, often requires a multimodality imaging approach. A
radiologist's ability to evaluate cardiac metastases hinges on an understanding
of the epidemiology, anatomy, and imaging features of this disease process.
CONCLUSION: On surveillance imaging of patients with cancer or when metastatic
disease is suspected, detection of metastatic disease may be greatly enhanced by
an understanding of which primary tumors metastasize to the heart and the most
common routes of spread.
PMID- 27490330
TI - JOURNAL CLUB: Patient Perception of Radiology and Radiologists: A Survey Analysis
of Academic and Community Institutions.
AB - OBJECTIVE: The objective of the present study is to evaluate patient
understanding of radiology and radiologists and to assess patient interest in
direct consultation with a radiologist. MATERIALS AND METHODS: A total of 1976
adult radiology outpatients at both a university and a nearby community hospital
were surveyed. After an initial survey was administered, educational material
with an attached follow-up survey was distributed to the patients. A McNemar test
was used to assess the difference between patients who correctly chose the
radiologist as the image interpreter before and after educational material was
provided, whereas a paired t test was used to test the difference between patient
levels of comfort with various image interpreters. RESULTS: Of the respondents,
84% expressed interest in meeting with a radiologist, with 43% willing to pay $0,
37% willing to pay $10-$30, and 20% willing to pay $40 or more to do so. Small
percentages of respondents incorrectly identified ultrasound (10%) and MRI (45%)
examinations as using radiation, whereas larger percentages of respondents
correctly identified radiography (87%), CT (63%), and nuclear medicine imaging
(62%) examinations as using radiation. A total of 73% of respondents (1002/1369)
initially chose the radiologist as the image interpreter; this percentage
improved to 81% (1109/1369) after the respondents received educational material
(p < 0.0001). Both before and after educational material was provided,
respondents had a statistically significantly lower mean (+/- SD) comfort level
score (scale, 1-10) when faced with the prospect of a nurse or physician
assistant interpreting their examination versus a trained physician (i.e., a
radiologist) (mean score, 5.2 +/- 3.27 and 9.4 +/- 1.47, respectively, before
education [p < 0.0001] and 5.2 +/- 2.94 and 9.56 +/- 1.24, respectively, after
education [p < 0.0001]). CONCLUSION: The level of comfort with radiologists as
image interpreters was statistically significantly higher than the level of
comfort with nonradiologist interpreters, and most patients were interested in
meeting with radiologists. Educational material improved patient perception and
knowledge of radiology.
PMID- 27490331
TI - Melatonin Receptor 1 Deficiency Affects Feeding Dynamics and Pro-Opiomelanocortin
Expression in the Arcuate Nucleus and Pituitary of Mice.
AB - BACKGROUND/METHODS: Melatonin, the neurohormone for darkness, mediates
photoperiod-dependent changes in physiology and behavior by targeting specific
membrane-bound receptors (MT1 and MT2). In the present study, we investigated the
impact of MT1 receptor deficiency on feeding behavior, locomotor activity and
mRNA expression levels encoding for the polypeptide pro-opiomelanocortin (Pomc)
and neuropeptide Y (Npy) in the hypothalamic arcuate nucleus (ARC) and the
adenohypophysis [pars distalis (PD) and pars intermedia (PI)] in a comparison
between wild-type (WT) and MT1-deficient (MT1-/-) mice. RESULTS: The MT1-/- mice
spent significantly more time feeding than the WT mice, while the general
locomotor behavior, body weight and the total amount of food consumed did not
differ between both genotypes. The nocturnal expression levels of Pomc in the ARC
and PD were significantly higher in WT as compared to MT1-/- mice and exogenous
melatonin administered during the light phase stimulated Pomc expression in WT
mice only. No differences were found between WT and MT1-/- mice with regard to
Pomc expression levels in the PI. CONCLUSION: Thus, the MT1-mediated signaling
stimulates Pomc expression in a region-specific pattern. Since the MT1-mediated
changes in Pomc expression do not elicit direct orexigenic or anorexigenic
effects, such effects are obviously mediated by regulatory systems downstream of
the Pomc mRNA (e.g. cleavage and release of POMC derivatives), which are
independent of MT1 signaling.
PMID- 27490332
TI - Does Ventriculoperitoneal Shunting Improve Thyroid Hormone Levels in
Hydrocephalic Newborns?
AB - OBJECTIVE/AIM: The aim of this report was to investigate the effect of
ventriculoperitoneal shunt insertion for the treatment of hydrocephalus on
thyroid hormones in the first 3 months of life. METHODS: Thyroid-stimulating
hormone (TSH), free T3 (fT3), and free T4 (fT4) levels were compared at 7 days
(preoperatively) and at 30 and 90 days (postoperatively) after birth between 25
ventriculoperitoneal shunt-inserted hydrocephalic newborns and 20 healthy
newborns. RESULTS: The TSH level at 7 days was higher in the hydrocephalic
patient group (6.33 uIU) compared to the control group (3.76 uIU). This value was
significantly decreased at 90 days in the ventriculoperitoneal shunt-inserted
newborns (2.35 uIU) compared to the control group (3.33 uIU; p < 0.05). There
were no significant differences between time points for fT4 and fT3 values in the
patient group or for TSH, fT4, and fT3 values in the control group. CONCLUSION:
We propose that a ventriculoperitoneal shunt inserted in the early period of life
may have beneficial effects on thyroid hormones.
PMID- 27490333
TI - Combination of a Cyano Migration Strategy and Alkene Difunctionalization: The
Elusive Selective Azidocyanation of Unactivated Olefins.
AB - A conceptually new, efficient, and metal-free approach for the challenging
azidocyanation of unactivated alkenes is presented. The strategy of
intramolecular distal cyano migration is combined with alkene difunctionalization
for the first time. A variety of useful azido-substituted alkyl nitriles are
prepared in good yields and, most importantly, with exquisite regio- and stereo
selectivities.
PMID- 27490334
TI - A novel screening method for 64 new psychoactive substances and 5 amphetamines in
blood by LC-MS/MS and application to real cases.
AB - Identification and quantification of new psychoactive substances (NPS), both in
biological and non-biological samples, represent a hard challenge for forensic
toxicologists. NPS are increasingly emerging on illegal drug market. Many cases
of co-consumption of NPS and other substances have also been reported. Hence, the
development of analytical methods aiming at the detection of a broad-spectrum of
compounds (NPS and "traditional" drugs) could be helpful. In this paper, a fully
validated screening method in blood for the simultaneous detection of 69
substances, including 64 NPS (28 synthetic cannabinoids, 19 synthetic cathinones,
5 phenethylamines, 3 indanes, 2 piperazines, 2 tryptamines, 2 phencyclidine,
methoxetamine, ketamine and its metabolite) and 5 amphetamines (amphetamine,
methamphetamine, MDMA, MDA, 3,4-methylenedioxy-N-ethylamphetamine - MDEA-) by a
dynamic multiple reaction monitoring analysis through liquid chromatography -
tandem mass spectrometry (LC-MS/MS) is described. This method is very fast, easy
to perform and cheap as it only requires the deproteinization of 200MUL of blood
sample with acetonitrile. The chromatographic separation is achieved with a C18
column. The analysis is very sensitive, with limits of quantification ranging
from 0.1 to 0.5ng/mL. The method is linear from 1 to 100ng/mL and the coefficient
of determination (R(2)) was always above 0.9900. Precision and accuracy were
acceptable at any quality control level and recovery efficiency range was 72
110%. Matrix effects did not negatively affect the analytical sensitivity. This
method was successfully applied to three real cases, allowing identification and
quantification of: mephedrone and methamphetamine (post-mortem); ketamine, MDMA
and MDA (post-mortem); AB-FUBINACA (ante-mortem).
PMID- 27490336
TI - Luminescent Covalent Organic Frameworks Containing a Homogeneous and
Heterogeneous Distribution of Dehydrobenzoannulene Vertex Units.
AB - Finding new ways to construct crystalline multiple-component covalent organic
frameworks (COFs) has become an important focus. Herein we report the synthesis
of three novel COFs containing a homogeneous and heterogeneous distribution of pi
conjugated dehydrobenzoannulene (DBA) vertex units. The COFs were synthesized by
reacting different ratios of C3-symmetric DBA catechol monomers with C2-symmetric
pyrene-2,7-diboronic acid (PDBA) to yield three COFs, Py-DBA-COF 1, Py-DBA-COF 2,
and Py-MV-DBA-COF. All three materials are highly crystalline and display unique
luminescent properties in the solid state.
PMID- 27490335
TI - Sulfoxide-Based Enantioselective Nazarov Cyclization: Divergent Syntheses of (+)
Isopaucifloral F, (+)-Quadrangularin A, and (+)-Pallidol.
AB - The synthesis of enantiomerically pure 3-aryl substituted indanones is developed
using an enantioselective sulfoxide-based Knoevenagel condensation/Nazarov
cyclization procedure. After the reductive desulfonation of the methyl para-tolyl
sulfoxide-containing chiral auxiliary under mild conditions, selected
enantiomerically pure indanone is used for the divergent total syntheses of three
resveratrol natural products (+)-isopaucifloral F, (+)-quadrangularin A, and (+)
pallidol.
PMID- 27490341
TI - Beyond GRACE: Using Satellite Data for Groundwater Investigations.
PMID- 27490342
TI - Tracing the origin of beer samples by NMR and chemometrics: Trappist beers as a
case study.
AB - An NMR and chemometric analytical approach to classify beers according to their
brand identity was developed within the European TRACE project (FP6-2003-FOOD-2
A, contract number: 0060942). Rochefort 8 Trappist beers (47 samples), other
Trappist beers (76 samples) and non-Trappist beers (110 samples) were analyzed by
1 H NMR spectroscopy. Selected NMR signals were measured and used to build
classification models. Three different classification problems were identified,
namely Trappist versus non-Trappist, Rochefort versus Non-Rochefort, and
Rochefort 8 versus non-Rochefort 8. In all the three cases, both a discriminant
and a modeling approaches were followed, using partial least squares discriminant
analysis (PLS-DA) and soft independent modeling of class analogies (SIMCA),
respectively, leading to very high classification accuracy as evaluated by
external validation. Information regarding chemical composition was also
obtained: Trappist beers contain a higher amount of formic and pyruvic acids and
a lower amount of acetic acid and alanine with respect to non-Trappist ones.
Rochefort beers turned out to have also a higher content of propanol and
isopentanol with respect to non-Rochefort samples. Finally, Rochefort 8, shows
the highest content of pyruvic acid and the lowest content of gallic, fumaric,
acetic acids, adenosine, uridine, 2-phenylethanol, GABA, and alanine.
PMID- 27490343
TI - Microarray-Based Analysis of Methylation of 1st Trimester Trisomic Placentas from
Down Syndrome, Edwards Syndrome and Patau Syndrome.
AB - Methylation-based non-invasive prenatal testing of fetal aneuploidies is an
alternative method that could possibly improve fetal aneuploidy diagnosis,
especially for trisomy 13(T13) and trisomy 18(T18). Our aim was to study the
methylation landscape in placenta DNA from trisomy 13, 18 and 21 pregnancies in
an attempt to find trisomy-specific methylation differences better suited for non
invasive prenatal diagnosis. We have conducted high-resolution methylation
specific bead chip microarray analyses assessing more than 450,000 CpGs analyzing
placentas from 12 T21 pregnancies, 12 T18 pregnancies and 6 T13 pregnancies. We
have compared the methylation landscape of the trisomic placentas to the
methylation landscape from normal placental DNA and to maternal blood cell DNA.
Comparing trisomic placentas to normal placentas we identified 217 and 219
differentially methylated CpGs for CVS T18 and CVS T13, respectively (delta
beta>0.2, FDR<0.05), but only three differentially methylated CpGs for T21.
However, the methylation differences was only modest (delta beta<0.4), making
them less suitable as diagnostic markers. Gene ontology enrichment analysis
revealed that the gene set connected to theT18 differentially methylated CpGs was
highly enriched for GO terms related to"DNA binding" and "transcription factor
binding" coupled to the RNA polymerase II transcription. In the gene set
connected to the T13 differentially methylated CpGs we found no significant
enrichments.
PMID- 27490345
TI - Liver resection for non-colorectal non-neuroendocrine metastases.
AB - OBJECTIVE: Liver resections for non-colorectal non-neuroendocrine liver
metastases (NCNELM) are gaining popularity. This study examines the outcomes of
liver resections in patients with NCNELM in an Australian hospital. METHOD: A
database search identified 21 attempted liver resections on 20 patients (12 men,
eight women, mean age: 63.1) from 1998 to 2013. A retrospective analysis
considered patient demographics and primary malignancy details. Complication
rates were compared to those for colorectal metastases at the same institution.
Kaplan-Meier curves were used to plot overall survival. RESULTS: Complete
resection was achieved in 16 of the 21 operations with 13 cases having proven
metastases (three cases were benign lesions on final histology). Primary cancers
were gastric (n = 4), gall bladder/bile duct (n = 3), renal (n = 3), soft tissue
sarcoma (n = 3), melanoma (n = 2), pancreatic (n = 2), anal (n = 2), breast (n =
1) and unknown (n = 1). Primary histology types were adenocarcinoma (n = 10),
sarcoma (n = 3), renal cell (n = 3), squamous cell (n = 2), melanoma (n = 2) and
gastrointestinal stromal tumour (n = 1). There was no peri-operative mortality.
Significant post-operative complications (Clavien-Dindo Grade III or more)
occurred in six patients (28.5%). Overall survival at 2 and 5 years was 46.2% and
30.8%, respectively, for all 21 cases of attempted resection, and 51.9% and
34.6%, respectively, for the 13 cases of complete resection of malignant
metastases. CONCLUSIONS: This study produced comparable 5-year survival rates to
those reported after liver resection for colorectal metastases and in other
studies on NCNELM. Complication rates were comparable to those for colorectal
liver metastasis resection at the same institution.
PMID- 27490344
TI - E2F1 Hinders Skin Wound Healing by Repressing Vascular Endothelial Growth Factor
(VEGF) Expression, Neovascularization, and Macrophage Recruitment.
AB - BACKGROUND: Refractory surface of wound and dermal chronic ulcer are largely
attributed to poor neovascularization. We have previously shown that E2F1
suppresses VEGF expression in the ischemic heart, and that genetic deletion of
E2F1 leads to better cardiac recovery. However, whether E2F1 has a role in dermal
wound healing is currently not known. METHODS AND RESULTS: Skin wounds were
surgically induced in E2F1-null (E2F1-/-) mice and WT littermates. E2F1-/-
displayed an accelerated wound healing including wound closure, dermal thickening
and collagen deposition, which was associated with an increased endothelial cell
proliferation and greater vessel density in the border zone of the wound.
Furthermore, more macrophages were recruited to the skin lesions and the level of
VEGF expression was markedly higher in E2F1-/- than in WT mice. CONCLUSIONS: E2F1
hinders skin wound healing by suppressing VEGF expression, neovascularization,
and macrophage recruitment. Strategies that target E2F1 may enhance wound
healing.
PMID- 27490346
TI - The Influence of Sex and Season on Conspecific Spatial Overlap in a Large,
Actively-Foraging Colubrid Snake.
AB - Understanding the factors influencing the degree of spatial overlap among
conspecifics is important for understanding multiple ecological processes.
Compared to terrestrial carnivores, relatively little is known about the factors
influencing conspecific spatial overlap in snakes, although across snake taxa
there appears to be substantial variation in conspecific spatial overlap. In this
study, we described conspecific spatial overlap of eastern indigo snakes
(Drymarchon couperi) in peninsular Florida and examined how conspecific spatial
overlap varied by sex and season (breeding season vs. non-breeding season). We
calculated multiple indices of spatial overlap using 6- and 3-month utilization
distributions (UD) of dyads of simultaneously adjacent telemetered snakes. We
also measured conspecific UD density values at each telemetry fix and modeled the
distribution of those values as a function of overlap type, sex, and season using
generalized Pareto distributions. Home range overlap between males and females
was significantly greater than overlap between individuals of the same sex and
male home ranges often completely contained female home ranges. Male home ranges
overlapped little during both seasons, whereas females had higher levels of
overlap during the non-breeding season. The spatial patterns observed in our
study are consistent with those seen in many mammalian carnivores, in which low
male-male overlap and high inter-sexual overlap provides males with greater
access to females. We encourage additional research on the influence of prey
availability on conspecific spatial overlap in snakes as well as the behavioral
mechanisms responsible for maintaining the low levels of overlap we observed.
PMID- 27490347
TI - Saturated Heavier Group 14 Compounds as sigma -Electron-Acceptor (Z-Type)
Ligands.
AB - This review article describes the chemistry of transition-metal complexes
containing heavier group 14 elements (Si, Ge, and Sn) as the sigma-electron
acceptor (Z-type) ligands and discusses the characteristics of bonds between the
transition metal and Z-type ligand. Moreover, we review the iridium hydride
mediated cleavage of E-X bonds (E=Si, Ge; X=F, Cl), where the key intermediates
are pentacoordinate silicon or germanium compounds bearing a dative M->E bond.
PMID- 27490349
TI - [Not Available].
PMID- 27490348
TI - A Genome-Wide Search for Greek and Jewish Admixture in the Kashmiri Population.
AB - The Kashmiri population is an ethno-linguistic group that resides in the Kashmir
Valley in northern India. A longstanding hypothesis is that this population
derives ancestry from Jewish and/or Greek sources. There is historical and
archaeological evidence of ancient Greek presence in India and Kashmir. Further,
some historical accounts suggest ancient Hebrew ancestry as well. To date, it has
not been determined whether signatures of Greek or Jewish admixture can be
detected in the Kashmiri population. Using genome-wide genotyping and admixture
detection methods, we determined there are no significant or substantial signs of
Greek or Jewish admixture in modern-day Kashmiris. The ancestry of Kashmiri
Tibetans was also determined, which showed signs of admixture with populations
from northern India and west Eurasia. These results contribute to our
understanding of the existing population structure in northern India and its
surrounding geographical areas.
PMID- 27490350
TI - [Not Available].
PMID- 27490351
TI - [Higher - Further - Faster].
AB - The striated skeletal muscles consist of different myocytes that have different
metabolic and contractile characteristics. They react in a specific way to
difference training stimuli: adaptations as a result of endurance training
trigger an increase in mitochondria and lead to an intensified oxidative
metabolism. Adaptations as a result of strength training result in increased
protein biosynthesis and hypertrophy of the skeletal myocytes. About 50 % of the
adaptation associated with endurance training are due to genetic factors.The
molecular mechanisms that underlie the training adaptations are currently the
subject of intense research. They comprise complex interrelated systems with a
series of key components. Understanding molecular switches and signalling
pathways gives rise to the assumption that the combination of simultaneous
strength training and endurance training is counterproductive. The combination of
both these forms of training possible weakens the effect on muscle mass and
muscle strength. Consequently the recommendation is to plan for enough of time
intervals between strength training and endurance training.
PMID- 27490352
TI - [Fast Response Training in Youth Soccer Players].
AB - BACKGROUND: Injuries of the knee and ankle joint are a serious ongoing problem in
soccer. Although there is a variety of prevention programmes, a significant
reduction of severe knee injuries has not been observed. Therefore, current
strategies for diagnostics and training need to be re-evaluated. OBJECTIVE: Our
study aimed to test a totally new intervention strategy (fast response training
on the SpeedCourt). The efficiency of this method was evaluated with youth soccer
athletes. MATERIALS AND METHODS: 24 young male class A athletes (mean age 18.0 +/
0.7 years) of a local soccer team underwent SpeedCourt training for 7 weeks (1
training session per week = TS) during the regular season of competition. TS
contained life-kinetic elements (time of exercise: 15 - 30 seconds, break: 2
minutes) and included a warm-up phase (15 minutes) and fast response training on
the SpeedCourt (30 minutes). The players were tested on the SpeedCourt with
different tests (Counter Movement Jump (CMJ), shuttle run, tapping, 10-second
sprint) before and after the training programme. RESULTS: The univariate single
factor analysis of variance showed significant improvements in all test
parameters (eta(2)> 0.10). The range varied between eta(2) = 0.106 (time of
ground contact right leg) und eta(2) = 0.730 (reaction time right leg). We did
not find any relevant correlations between the tests and parameters. The number
of injury-related accidents involving the lower extremities was reduced by about
50 % during defined periods of time. CONCLUSION: Our data revealed that training
with fast responses at the SpeedCourt system clearly improved speed and speed
strength performance of young soccer athletes, which is remarkable given the low
intensity of influences (one TS per week). The increase in performance was
accompanied by a significant reduction of the injury rate.
PMID- 27490353
TI - [Characteristics of Nutrition in Competitive Sports, Ranging from Leisure
Activities to High-Performance Athletics].
AB - Nutrition has a crucial influence on physical and mental performance ability and
is an important measure along sidetraining in high-performance athletes. However,
this form of nutritionis not applicable for every athlete and in every situation.
The question of optimal nutrition requires involvement with the particular type
of sports, an athlete's current training stage, and athletes' individual
requirements and objectives. Implementation takes time and individual motivation
on the part of athletes and the specialist staff who engage intensively with the
nutritional needs of athletes. In addition to adequate energy provision, it is
important to divide the energy sensibly among the energy sources carbohydrates,
fats, and protein. Performance athletes' higher need for protein can usually be
covered in their regular diet; supplements are needed only in exceptional cases.
Studies have shown that small amounts of 15 - 25 g protein are sensible after
weight training, in order to stimulate muscle protein synthesis. The need for
carbohydrates increases dynamically with the intensity and duration of physical
exertion. A sufficient supply is crucial for achieving maximum performance. Low
carb diets are unsuitable for performance athletes. So called low-glycogen
training, however, can lead to better adjustment/adaptation processes in selected
training stages and can increase performance ability.
PMID- 27490354
TI - [Zika Virus - Impact on the 2016 Olympic Games in Rio de Janeiro].
AB - There is an ongoing discussion in the media about the Zika virus and the question
of whether or not athletes and visitors will be at risk of an infection during
the Olympic Games in Rio de Janeiro in 2016. According to an assessment published
on 31 May 2016 by the IOC and the WHO, participants and visitors have no reason
to panic. However, increasing public pressure has caused the WHO to re-evaluate
the current situation, and further recommendations will likely be given before
the Olympic Games start. The current facts are as follows: 1) The Olympic Summer
Games will be held during the winter months in Brazil, when the appearance of
mosquitoes is expected to be low. 2) Extensive use of insecticides every 6 to 8
weeks in Rio de Janeiro and all Olympic venues has almost eradicated the mosquito
population. 3) Individual protection of athletes, trainers and visitors is
crucial (wearing appropriate clothing with skin coverage, sleeping under mosquito
nets, using contact insecticides for clothing and mosquito nets, and applying
insect repellents on a regular basis). 4) Pregnant women should avoid travelling
to any country with current Zika virus activity. In sum, the risk to incur a Zika
virus infection during the Olympic Games in Rio de Janeiro will likely be
comparable to the risk in other countries where cases of Zika virus infections
are registered.
PMID- 27490355
TI - [Rehabilitation of Ligamentous Elbow Instability in Athletes].
AB - Ligamentous instability of the elbow is a common pathology affecting athletes in
different types of sports. It may lead to a permanent impairment of an athlete's
ability to train and compete. The advancements made in arthroscopic,
biomechanical and clinical diagnostic procedures allow for a better understanding
of the etiology of elbow discomfort. As a result, ligamentous instability has
been increasingly identified as a reason for acute and chronic pain in athletes.
This article provides an overview of the etiology as well as diagnostic and
rehabilitative procedures for ligamentous instability of the elbow in athletes
and presents principles of rehabilitation in patients with symptomatic elbow
instability.
PMID- 27490356
TI - Groin Pain and Muscular Imbalance of Quadriceps and Hamstrings in an Elite Soccer
Player - A Case Study.
AB - Soccer and football players are exposed to a high risk of groin pain. In some
cases, the pubic symphysis is the origin of the problems.This article presents a
case report of a young elite soccer player who, over a period of two years,
suffered from pain in the groin and symphysis area. The right leg was the kicking
leg. Imaging techniques did not reveal pathological findings. Sports hernia,
osteomyelitis, enthesopathy, adductor tendonitis, and muscle sprains, as well as
rheumatic or urogenital disorders were excluded.A 3 D posture analysis was
performed to examine the statics of the body and pelvis. The maximum isometric
strength of the left and right leg adductors and abductors, as well as the knee
flexors and extensors were measured.We found a muscular imbalance resulting from
the type of sport the athlete engaged in with an unfavourable ratio between the
right knee extensor and flexor muscles. Comparing sides, an imbalance was also
identified between the right and left knee extensor. This imbalance resulted in a
one-sided forward tilt of the right hemi-pelvis. This pelvic torsion may lead to
an increase in shear forces in the pubic symphysis, which we suspected to be the
reason for the recurring problems.After three months of specific training
exercises, the pelvic position was harmonised and the muscular imbalances were
significantly reduced. Even 6 months after completion of the specific training
exercises, the player remained without complaints despite his unvaried soccer
training intensity.Causal treatment of functional pain in the groin or symphysis
area should take into account the ipsilateral and contralateral strength ratios
of the knee extensors and flexors as well as the three-dimensional position of
the pelvis.
PMID- 27490357
TI - Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: A Regioselective
Sulfenylation of Imidazoheterocycles Using Dimethyl Sulfoxide as an Oxidant.
AB - A regioselective formation of C-S bonds has been achieved using a cross
dehydrogenative coupling (CDC) protocol using iodine as a catalyst and dimethyl
sulfoxide as an oxidant under green chemistry conditions. This strategy employs
the reaction of easily available heterocyclic thiols or thiones with
imidazoheterocycles. This protocol provides an efficient, mild, and inexpensive
method for sulfenylation of imidazoheterocycles with a diverse range of
heterocyclic thiols and heterocyclic thiones.
PMID- 27490358
TI - Is Satisfaction with the Acute-Care Experience Higher amongst Consumers Treated
in the Private Sector? A Survey of Public and Private Sector Arthroplasty
Recipients.
AB - BACKGROUND: Consumer satisfaction with the acute-care experience could reasonably
be expected to be higher amongst those treated in the private sector compared to
those treated in the public sector given the former relies on high-level
satisfaction of its consumers and their subsequent recommendations to thrive. The
primary aims of this study were to determine, in a knee or hip arthroplasty
cohort, if surgery in the private sector predicts greater overall satisfaction
with the acute-care experience and greater likelihood to recommend the same
hospital. A secondary aim was to determine whether satisfaction across a range of
service domains is also higher in the private sector. METHODS: A telephone survey
was conducted 35 days post-surgery. The hospital cohort comprised eight public
and seven private high-volume arthroplasty providers. Consumers rated overall
satisfaction with care out of 100 and likeliness to recommend their hospital on a
5-point Likert scale. Additional Likert-style questions were asked covering
specific service domains. Generalized estimating equation models were used to
analyse overall satisfaction (dichotomised as >= 90 or < 90) and future
recommendations for care (dichotomised as 'definitely recommend' or 'other'),
whilst controlling for covariates. The proportions of consumers in each sector
reporting the best Likert response for each individual domain were compared using
non-parametric tests. RESULTS: 457 survey respondents (n = 210 private) were
included. Less patient-reported joint impairment pre-surgery [OR 1.03 (95% CI
1.01-1.05)] and absence of an acute complication (OR 2.13 95% CI 1.41-3.23)
significantly predicted higher overall satisfaction. Hip arthroplasty [OR 1.84
(1.1-2.96)] and an absence of an acute complication [OR 2.31 (1.28-4.17]
significantly predicted greater likelihood for recommending the hospital. The
only care domains where the private out-performed the public sector were
hospitality (46.7 vs 35.6%, p <0.01) and frequency of surgeon visitation (76.4 vs
65.8%, p = 0.03). CONCLUSIONS: Arthroplasty consumers treated in the private
sector are not more satisfied with their acute-care experience nor are they more
likely to recommend their hospital provider. Rather, avoidance of complications
in either sector appears to result in improved satisfaction as well as a greater
likelihood that patients would recommend their hospital provider.
PMID- 27490359
TI - Constrained Cyclopeptides: Biaryl Formation through Pd-Catalyzed C-H Activation
in Peptides-Structural Control of the Cyclization vs. Cyclodimerization Outcome.
AB - A series of short tryptophan-phenylalanine peptides containing an iodo
substituent on the phenyl ring was subjected to Pd-catalyzed CH activation
reactions to give the corresponding aryl-indole coupled products. Two types of
adducts were generated: cyclomonomer and cyclodimeric peptides; no evidence of
oligo- or polymerization products was detected. Contrary to standard peptide
macrocyclizations, the factors controlling the fate of the reaction are the
number of amino acids between the aromatic residues and the regiochemistry of the
parent iodo derivative, independent of both the concentration and the cyclization
mode. The method is general and allows access to novel biaryl peptidic
topologies, which have been fully characterized.
PMID- 27490360
TI - Mycoplasma pneumoniae triggering the Guillain-Barre syndrome: A case-control
study.
AB - OBJECTIVE: Guillain-Barre syndrome (GBS) is an acute postinfectious immune
mediated polyneuropathy. Although preceding respiratory tract infections with
Mycoplasma pneumoniae have been reported in some cases, the role of M. pneumoniae
in the pathogenesis of GBS remains unclear. We here cultured, for the first time,
M. pneumoniae from a GBS patient with antibodies against galactocerebroside
(GalC), which cross-reacted with the isolate. This case prompted us to unravel
the role of M. pneumoniae in GBS in a case-control study. METHODS: We included
189 adults and 24 children with GBS and compared them to control cohorts for
analysis of serum antibodies against M. pneumoniae (n = 479) and GalC (n = 198).
RESULTS: Anti-M. pneumoniae immunoglobulin (Ig) M antibodies were detected in GBS
patients and healthy controls in 3% and 0% of adults (p = 0.16) and 21% and 7% of
children (p = 0.03), respectively. Anti-GalC antibodies (IgM and/or IgG) were
found in 4% of adults and 25% of children with GBS (p = 0.001). Anti-GalC
positive patients showed more-frequent preceding respiratory symptoms, cranial
nerve involvement, and a better outcome. Anti-GalC antibodies correlated with
anti-M. pneumoniae antibodies (p < 0.001) and cross-reacted with different M.
pneumoniae strains. Anti-GalC IgM antibodies were not only found in GBS patients
with M. pneumoniae infection, but also in patients without neurological disease
(8% vs 9%; p = 0.87), whereas anti-GalC IgG was exclusively found in patients
with GBS (9% vs 0%; p = 0.006). INTERPRETATION: M. pneumoniae infection is
associated with GBS, more frequently in children than adults, and elicits anti
GalC antibodies, of which specifically anti-GalC IgG may contribute to the
pathogenesis of GBS. Ann Neurol 2016;80:566-580.
PMID- 27490361
TI - Non-Smoking Tobacco Affects Endothelial Function in Healthy Men in One of the
Largest Health Studies Ever Performed; The Nord-Trondelag Health Study in Norway;
HUNT3.
AB - BACKGROUND: Oral tobacco (snuff) is taking a large market share in Scandinavia,
especially with young users. However, long-term health effects are unknown. Small
studies show association between snuff and reduced endothelial function,
representing an early stage of vascular injury that often precedes manifest
cardiovascular disease by several years. We therefore determined the associations
between snuff and endothelial function in a large sample of healthy Norwegian
men. METHODS AND DESIGN: In the Fitness substudy of the Nord-Trondelag Health
Study (HUNT3), endothelial function was measured by flow-mediated dilation (FMD).
Aerobic fitness was measured by peak oxygen uptake (VO2peak). A cross-sectional
design including 1 592 self-reported healthy men compared these observations with
records of present tobacco use, standard cardiovascular risk factors, and
socioeconomic status, using general linear models. RESULTS: FMD was lower in
snuff users (FMD: 4.12%, 3.63, 4.61) compared to non-users (FMD: 4.52%, 4.27,
4.78) after adjustment for age (difference: -0.57%, -1.12, -0.01). After further
adjustment for potential confounders, FMD still tended to be lower in snuff users
than in non-users (difference: -0.53%, -1.09, 0.02). This difference was even
more pronounced in the inactive snuff users (-0.83%, -1.59, -0.06) and in the low
fit snuff users (-0.74%, CI -0.55, 0.079). CONCLUSIONS: Oral tobacco is
associated with a tendency towards reduced endothelial function, indicating
vascular changes that precede cardiovascular disease. The strongest associations
were found in men with low physical activity or reduced aerobic fitness.
PMID- 27490362
TI - Remarkable In Vivo Nonlinear Photoacoustic Imaging Based on Near-Infrared Organic
Dyes.
AB - Two near-infrared dyes featuring good dispersion and light-harvesting property
present a remarkable nonlinear photoacoustic response in vitro and in vivo
comparing with conventional gold nanorods. This study benefits the fabrication of
drug delivery platforms with accurate targeting and control effect under
photoacoustic image guidance.
PMID- 27490363
TI - Stability Analysis of SIR Model with Distributed Delay on Complex Networks.
AB - In this paper, by taking full consideration of distributed delay, demographics
and contact heterogeneity of the individuals, we present a detailed analytical
study of the Susceptible-Infected-Removed (SIR) epidemic model on complex
population networks. The basic reproduction number [Formula: see text] of the
model is dominated by the topology of the underlying network, the properties of
individuals which include birth rate, death rate, removed rate and infected rate,
and continuously distributed time delay. By constructing suitable Lyapunov
functional and employing Kirchhoff's matrix tree theorem, we investigate the
globally asymptotical stability of the disease-free and endemic equilibrium
points. Specifically, the system shows threshold behaviors: if [Formula: see
text], then the disease-free equilibrium is globally asymptotically stable,
otherwise the endemic equilibrium is globally asymptotically stable. Furthermore,
the obtained results show that SIR models with different types of delays have
different converge time in the process of contagion: if [Formula: see text], then
the system with distributed time delay stabilizes fastest; while [Formula: see
text], the system with distributed time delay converges most slowly. The
validness and effectiveness of these results are demonstrated through numerical
simulations.
PMID- 27490365
TI - Racial/Ethnic Disparities in Primary Care Quality Among Type 2 Diabetes Patients,
Medical Expenditure Panel Survey, 2012.
AB - INTRODUCTION: Racial and ethnic disparities exist in diabetes prevalence, access
to diabetes care, diabetes-related complications and mortality rates, and the
quality of diabetes care among Americans. We explored racial and ethnic
disparities in primary care quality among Americans with type 2 diabetes.
METHODS: We analyzed data on adults with type 2 diabetes derived from the
household component of the 2012 Medical Expenditure Panel Survey. Multiple
regression and multivariate logistic regressions were used to examine the
association between race/ethnicity and primary care attributes related to first
contact, longitudinality, comprehensiveness, and coordination, and clusters of
confounding factors were added sequentially. RESULTS: Preliminary findings
indicated differences in primary care quality between racial/ethnic minorities
and whites across measures of first contact, longitudinality, comprehensiveness,
and coordination. After controlling for confounding factors, these differences
were no longer apparent; all racial/ethnic categories showed similar rates of
primary care quality according to the 4 primary care domains of interest in the
study. CONCLUSION: Results indicate equitable primary care quality for type 2
diabetes patients across 4 key domains of primary care after controlling for
socioeconomic characteristics. Additional research is necessary to support these
findings, particularly when considering smaller racial/ethnic groups and
investigating outcomes related to diabetes.
PMID- 27490366
TI - Health and Nutrition Literacy and Adherence to Treatment in Children,
Adolescents, and Young Adults With Chronic Kidney Disease and Hypertension, North
Carolina, 2015.
AB - INTRODUCTION: Adherence to treatment and dietary restrictions is important for
health outcomes of patients with chronic/end-stage kidney disease and
hypertension. The relationship of adherence with nutritional and health literacy
in children, adolescents, and young adults is not well understood. The current
study examined the relationship of health literacy, nutrition knowledge,
nutrition knowledge-behavior concordance, and medication adherence in a sample of
children and young people with chronic/end-stage kidney disease and hypertension.
METHODS: We enrolled 74 patients (aged 7-29 y) with a diagnosis of chronic/end
stage kidney disease and hypertension from the University of North Carolina
Kidney Center. Participants completed instruments of nutrition literacy (Disease
Specific Nutrition Knowledge Test), health literacy (Newest Vital Sign),
nutrition behavior (Nutrition Knowledge-Behavior Concordance Scale), and
medication adherence (Morisky Medication Adherence Scale). Linear and binary
logistic regressions were used to test the associations. RESULTS: In univariate
comparisons, nutrition knowledge was significantly higher in people with adequate
health literacy. Medication adherence was related to nutrition knowledge and
nutrition knowledge-behavior concordance. Multivariate regression models
demonstrated that knowledge of disease-specific nutrition restrictions did not
significantly predict nutrition knowledge-behavior concordance scores. In
logistic regression, knowledge of nutrition restrictions did not significantly
predict medication adherence. Lastly, health literacy and nutrition knowledge
behavior concordance were significant predictors of medication adherence.
CONCLUSION: Nutrition knowledge and health literacy skills are positively
associated. Nutrition knowledge, health literacy, and nutrition knowledge
behavior concordance are positively related to medication adherence. Future
research should focus on additional factors that may predict disease-specific
nutrition behavior (adherence to dietary restrictions) in children and young
people with chronic conditions.
PMID- 27490367
TI - Lessons From the Community-Centered Health Home Demonstration Project: Patient
Centered Medical Homes Can Improve Health Conditions in Their Surrounding
Communities.
PMID- 27490364
TI - High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol
Preference in Bidirectionally Selected Rat Model.
AB - Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use
Disorder) in human have yet to provide a clear view on potential genomic
etiologies. To address this issue, we sequenced a replicated animal model system
bidirectionally-selected for alcohol preference (AP). This model is uniquely
suited to map genetic effects with high reproducibility, and resolution. The
origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB)
with a corresponding high level of resolution. We sequenced DNAs from 40 samples
(10 per line of each replicate) to determine allele frequencies and HB. We
achieved ~46X coverage per line and replicate. Excessive differentiation in the
genomic architecture between lines, across replicates, termed signatures of
selection (SS), were classified according to gene and region. We identified SS in
930 genes associated with AP. The majority (50%) of the SS were confined to
single gene regions, the greatest numbers of which were in promoters (284) and
intronic regions (169) with the least in exon's (4), suggesting that differences
in AP were primarily due to alterations in regulatory regions. We confirmed
previously identified genes and found many new genes associated with AP. Of those
newly identified genes, several demonstrated neuronal function involved in
synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a),
excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and
synapses (Snap29). This study not only reveals the polygenic architecture of AP,
but also emphasizes the importance of regulatory elements, consistent with other
complex traits.
PMID- 27490368
TI - Electronic Cigarette Use Among High School Students and Its Association With
Cigarette Use And Smoking Cessation, North Carolina Youth Tobacco Surveys, 2011
and 2013.
AB - INTRODUCTION: Although adolescent cigarette use continues to decline in the
United States, electronic cigarette (e-cigarette) use among adolescents has
escalated rapidly. This study assessed trends and patterns of e-cigarette use and
concurrent cigarette smoking and the relationships between e-cigarette use and
smoking cessation intentions and behaviors among high school students in North
Carolina. METHODS: Data came from high school students who completed the school
based, cross-sectional North Carolina Youth Tobacco Survey in 2011 (n = 4,791)
and 2013 (n = 4,092). This study assessed changes in prevalence of e-cigarette
and cigarette use from 2011 through 2013, and cessation-related factors
associated with those students' current and past use of e-cigarettes in 2013.
RESULTS: The prevalence of current e-cigarette use (use in the past 30 days)
significantly increased from 1.7% (95% CI, 1.3%-2.2%) in 2011 to 7.7% (95% CI,
5.9%-10.0%) in 2013. Among dual users, current e-cigarette use was negatively
associated with intention to quit cigarette smoking for good (relative risk ratio
[RRR] = 0.51; 95% CI, 0.29-0.87) and with attempts to quit cigarette smoking in
the past 12 months (RRR = 0.69; 95% CI, 0.49-0.97). Current e-cigarette smokers
were less likely than those who only smoked cigarettes to have ever abstained
from cigarette smoking for 6 months (RRR = 0.42; 95% CI, 0.21-0.82) or 1 year
(RRR = 0.21; 95% CI, 0.09-0.51) and to have used any kind of aids for smoking
cessation (RRR = 0.46; 95% CI, 0.29-0.74). CONCLUSION: Public health
practitioners and cessation clinic service providers should educate adolescents
about the risks of using any nicotine-containing products, including e
cigarettes, and provide adequate tobacco cessation resources and counseling to
adolescent tobacco users.
PMID- 27490369
TI - Circumventing Diffusion in Kinetically Controlled Solid-State Metathesis
Reactions.
AB - Solid-state diffusion is often the primary limitation in the synthesis of
crystalline inorganic materials and prevents the potential discovery and
isolation of new materials that may not be the most stable with respect to the
reaction conditions. Synthetic approaches that circumvent diffusion in solid
state reactions are rare and often allow the formation of metastable products. To
this end, we present an in situ study of the solid-state metathesis reactions
MCl2 + Na2S2 -> MS2 + 2 NaCl (M = Fe, Co, Ni) using synchrotron powder X-ray
diffraction and differential scanning calorimetry. Depending on the preparation
method of the reaction, either combining the reactants in an air-free environment
or grinding homogeneously in air before annealing, the barrier to product
formation, and therefore reaction pathway, can be altered. In the air-free
reactions, the product formation appears to be diffusion limited, with a number
of intermediate phases observed before formation of the MS2 product. However,
grinding the reactants in air allows NaCl to form directly without annealing and
displaces the corresponding metal and sulfide ions into an amorphous matrix, as
confirmed by pair distribution function analysis. Heating this mixture yields
direct nucleation of the MS2 phase and avoids all crystalline binary
intermediates. Grinding in air also dissipates a large amount of lattice energy
via the formation of NaCl, and the crystallization of the metal sulfide is a much
less exothermic process. This approach has the potential to allow formation of a
range of binary, ternary, or higher-ordered compounds to be synthesized in the
bulk, while avoiding the formation of many binary intermediates that may
otherwise form in a diffusion-limited reaction.
PMID- 27490370
TI - XPS Study of Ion Irradiated and Unirradiated UO2 Thin Films.
AB - XPS determination of the oxygen coefficient kO = 2 + x and ionic (U(4+), U(5+),
and U(6+)) composition of oxides UO2+x formed on the surfaces of differently
oriented (hkl) planes of thin UO2 films on LSAT (Al10La3O51Sr14Ta7) and YSZ
(yttria-stabilized zirconia) substrates was performed. The U 4f and O 1s core
electron peak intensities as well as the U 5f relative intensity before and after
the (129)Xe(23+) and (238)U(31+) irradiations were employed. It was found that
the presence of uranium dioxide film in air results in formation of oxide UO2+x
on the surface with mean oxygen coefficients kO in the range 2.07-2.11 on LSAT
and 2.17-2.23 on YSZ substrates. These oxygen coefficients depend on the
substrate and weakly on the crystallographic orientation. On the basis of the
spectral parameters it was established that uranium dioxide films AP2,3 on the
LSAT substrates have the smallest kO values, and from the XRD and EBSD results it
follows that these samples have a regular monocrystalline structure. The XRD and
EBSD results indicate that samples AP5-7 on the YSZ substrates have
monocrystalline structure; however, they have the highest kO values. The observed
difference in the kO values was probably caused by the different nature of the
substrates: the YSZ substrates provide 6.4% compressive strain, whereas (001)
LSAT substrates result only in 0.03% tensile strain in the UO2 films.
(129)Xe(23+) irradiation (92 MeV, 4.8 * 10(15) ions/cm(2)) of uranium dioxide
films on the LSAT substrates was shown to destroy both long-range ordering and
uranium close environment, which results in an increase of uranium oxidation
state and regrouping of oxygen ions in uranium close environment. (238)U(31+)
(110 MeV, 5 * 10(10), 5 * 10(11), 5 * 10(12) ions/cm(2)) irradiations of uranium
dioxide films on the YSZ substrates were shown to form the lattice damage only
with partial destruction of the long-range ordering.
PMID- 27490371
TI - IMAGING DIAGNOSIS-RADIOGRAPHY AND ULTRASONOGRAPHY OF BILATERAL CONGENITAL
URETEROVESICAL JUNCTION STENOSIS CAUSING HYDRONEPHROSIS AND HYDROURETER IN A
FERRET (MUSTELA PUTORIUS FURO).
AB - An 8-month-old neutered male ferret was presented for vaccination and preventive
treatment for adrenal gland disease. Abdominal ultrasound revealed severe
bilateral hydronephrosis and hydroureter. Excretory urography and negative
contrast cystography showed bilateral ureterovesical junction stenosis. Positive
retrograde cystography demonstrated right ureteral reflux. A subcutaneous
ureteral bypass was placed in the left kidney; however, it had to be removed 3
months later due to an obstruction and persistent urinary tract infection.
Bilateral ureteroneocystotomy was performed. Although congenital strictures are
uncommon in veterinary patients, they should be included in the differential
diagnosis in ferrets presenting with hydronephrosis and hydroureter of
undetermined cause.
PMID- 27490372
TI - Terahertz Time-Domain Spectroscopy of Thermoresponsive Polymers in Aqueous
Solution.
AB - The behavior of highly concentrated aqueous solutions of two thermoresponsive
polymers poly(N-isopropylacrylamide) (PNIPAm) and poly(N-vinylcaprolactam) (PVCL)
have been investigated by terahertz time-domain spectroscopy (THz-TDS).
Measurements have been performed for concentrations up to 20 wt %, over a
frequency range from 0.3 to 1.5 THz and for temperatures from 20 to 45 degrees C
including the zone for lower critical solution temperature (LCST). THz-TDS
enables the study of the behavior of water present in the solution (i.e., free or
bound to the polymer). From these measurements, in addition to phase transition
temperature, thermodynamic data such as variation of enthalpy and entropy can be
inferred. Thanks to these data, further insights upon the mechanism involved
during the dehydration phenomenon were obtained. These results were compared to
the ones issued from dynamic light scattering, spectroscopy, or microscopy
techniques to underline the interest to use THz-TDS as a powerful tool to
characterize the behavior of thermoresponsive polymers in highly concentrated
solutions.
PMID- 27490373
TI - Optimising Translational Research Opportunities: A Systematic Review and
Narrative Synthesis of Basic and Clinician Scientists' Perspectives of Factors
Which Enable or Hinder Translational Research.
AB - INTRODUCTION: Translational research is central to international health policy,
research and funding initiatives. Despite increasing use of the term, the
translation of basic science discoveries into clinical practice is not
straightforward. This systematic search and narrative synthesis aimed to examine
factors enabling or hindering translational research from the perspective of
basic and clinician scientists, a key stakeholder group in translational
research, and to draw policy-relevant implications for organisations seeking to
optimise translational research opportunities. METHODS AND RESULTS: We searched
SCOPUS and Web of Science from inception until April 2015 for papers reporting
scientists' views of the factors they perceive as enabling or hindering the
conduct of translational research. We screened 8,295 papers from electronic
database searches and 20 papers from hand searches and citation tracking,
identifying 26 studies of qualitative, quantitative or mixed method designs. We
used a narrative synthesis approach and identified the following themes: 1)
differing concepts of translational research 2) research processes as a barrier
to translational research; 3) perceived cultural divide between research and
clinical care; 4) interdisciplinary collaboration as enabling translation
research, but dependent on the quality of prior and current social relationships;
5) translational research as entrepreneurial science. Across all five themes,
factors enabling or hindering translational research were largely shaped by wider
social, organisational, and structural factors. CONCLUSION: To optimise
translational research, policy could consider refining translational research
models to better reflect scientists' experiences, fostering greater collaboration
and buy in from all types of scientists. Organisations could foster cultural
change, ensuring that organisational practices and systems keep pace with the
change in knowledge production brought about by the translational research
agenda.
PMID- 27490374
TI - Plant-Mediated Effects on Mosquito Capacity to Transmit Human Malaria.
AB - The ecological context in which mosquitoes and malaria parasites interact has
received little attention, compared to the genetic and molecular aspects of
malaria transmission. Plant nectar and fruits are important for the nutritional
ecology of malaria vectors, but how the natural diversity of plant-derived sugar
sources affects mosquito competence for malaria parasites is unclear. To test
this, we infected Anopheles coluzzi, an important African malaria vector, with
sympatric field isolates of Plasmodium falciparum, using direct membrane feeding
assays. Through a series of experiments, we then examined the effects of sugar
meals from Thevetia neriifolia and Barleria lupilina cuttings that included
flowers, and fruit from Lannea microcarpa and Mangifera indica on parasite and
mosquito traits that are key for determining the intensity of malaria
transmission. We found that the source of plant sugar meal differentially
affected infection prevalence and intensity, the development duration of the
parasites, as well as the survival and fecundity of the vector. These effects are
likely the result of complex interactions between toxic secondary metabolites and
the nutritional quality of the plant sugar source, as well as of host resource
availability and parasite growth. Using an epidemiological model, we show that
plant sugar source can be a significant driver of malaria transmission dynamics,
with some plant species exhibiting either transmission-reducing or -enhancing
activities.
PMID- 27490376
TI - Associations between functional FCGR2A R131H and FCGR3A F158V polymorphisms and
responsiveness to TNF blockers in spondyloarthropathy, psoriasis and Crohn's
disease: a meta-analysis.
AB - AIM: The aim of the current study was to investigate whether FCGR polymorphisms
are associated with responsiveness to anti-TNF-alpha therapy in patients with
spondyloarthropathy, psoriasis, and Crohn's disease. MATERIALS & METHODS: We
conducted a meta-analysis to evaluate the association between the functional
FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to TNF blockers.
RESULTS: The meta-analysis indicated that responsiveness to TNF blockers was
associated with the FCGR3A V allele (odds ratio: 3.308; 95% CI: 1.053-10.39; p =
0.040) and the FCGR2A RR + RH genotype (odds ratio: 3.904; p = 0.027) in patients
with a follow-up time of >=6 months. CONCLUSION: FCGR3A V and FCGR2A R allele
carriers show better responsiveness to anti-TNF-alpha therapy in patients with
follow-up times >=6 months.
PMID- 27490375
TI - Gateway Vectors for Simultaneous Detection of Multiple Protein-Protein
Interactions in Plant Cells Using Bimolecular Fluorescence Complementation.
AB - Bimolecular fluorescence complementation (BiFC) is widely used to detect protein
protein interactions, because it is technically simple, convenient, and can be
adapted for use with conventional fluorescence microscopy. We previously
constructed enhanced yellow fluorescent protein (EYFP)-based Gateway cloning
technology-compatible vectors. In the current study, we generated new Gateway
cloning technology-compatible vectors to detect BiFC-based multiple protein
protein interactions using N- and C-terminal fragments of enhanced cyan
fluorescent protein (ECFP), enhanced green fluorescent protein (EGFP), and
monomeric red fluorescent protein (mRFP1). Using a combination of N- and C
terminal fragments from ECFP, EGFP and EYFP, we observed a shift in the emission
wavelength, enabling the simultaneous detection of multiple protein-protein
interactions. Moreover, we developed these vectors as binary vectors for use in
Agrobacterium infiltration and for the generate transgenic plants. We verified
that the binary vectors functioned well in tobacco cells. The results demonstrate
that the BiFC vectors facilitate the design of various constructions and are
convenient for the detection of multiple protein-protein interactions
simultaneously in plant cells.
PMID- 27490377
TI - Development of melt electrohydrodynamic 3D printing for complex microscale poly
(epsilon-caprolactone) scaffolds.
AB - The replication of native hierarchical structures into synthetic scaffolds is
important to direct cell growth and tissue regeneration. However, most of the
existing scaffold strategies lack the capability to simultaneously realize the
controlled fabrication of macroscopic geometries as well as microscale
architectures with the scale similar to living cells. Here we developed a melt
electrohydrodynamic printing platform and verified its feasibility to fabricate
three-dimensional (3D) tissue-engineered scaffolds with complex curved geometries
and microscale fibrous structures. Melting temperature was studied to stably
print poly (epsilon-caprolactone) (PCL) filaments with the size of about 10 MUm,
which was precisely stacked into 3D straight walls with fine surface quality. By
adjusting stage moving speed and directions, 3D PCL scaffolds with curved
contours and predefined fiber orientations or spacing were successfully printed.
Biological experiments showed that the printed microscale scaffolds had good
biocompatibility and facilitated cellular proliferation and alignment in vitro.
It is envisioned that the melt electrohydrodynamic printing can potentially
provide an innovative tool to fabricate hierarchical scaffolds that mimic the
native tissue architectures in a multiscale level.
PMID- 27490378
TI - Ring Expansion and Skeletal Rearrangement of Propargyl Alcohol Substituted
Aziridines Induced by Ruthenium Complexes.
AB - The ring expansion and skeletal rearrangement of two types of propargyl alcohol
substituted aziridines with or without cycloalkane moieties was induced by a
ruthenium cyclopentadienyl phosphine complex. In the simple aziridine system with
no cycloalkane, the unique cycloisomerization process altered the absolute
connectivity of the two-carbon unit in the three-membered ring to give
organometallic products with substituted pyridine or dihydropyridine ligands. For
the aziridine on a cyclohexyl ring, the cycloisomerization process was controlled
by an interchange process between vinylidene and allenylidene species, thus
creating a better relative configuration of the aziridinyl and the alkynyl units.
This determines the stereochemistry of the metal carbene products of the
octahydroindole derivatives. The structures of five products were determined by X
ray diffraction analysis.
PMID- 27490379
TI - Two-Color Lateral Flow Assay for Multiplex Detection of Causative Agents Behind
Acute Febrile Illnesses.
AB - Acute undifferentiated febrile illnesses (AFIs) represent a significant health
burden worldwide. AFIs can be caused by infection with a number of different
pathogens including dengue (DENV) and Chikungunya viruses (CHIKV), and their
differential diagnosis is critical to the proper patient management. While rapid
diagnostic tests (RDTs) for the detection of IgG/IgM against a single pathogen
have played a significant role in enabling the rapid diagnosis in the point-of
care settings, the state-of-the-art assay scheme is incompatible with the
multiplex detection of IgG/IgM to more than one pathogen. In this paper, we
present a novel assay scheme that uses two-color latex labels for rapid multiplex
detection of IgG/IgM. Adapting this assay scheme, we show that 4-plex detection
of the IgG/IgM antibodies to DENV and CHIKV is possible in 10 min by using it to
correctly identify 12 different diagnostic scenarios. We also show that blue,
mixed, and red colorimetric signals corresponding to IgG, IgG/IgM, and IgM
positive cases, respectively, can be associated with distinct ranges of hue
intensities, which could be exploited by analyzer systems in the future for
making accurate, automated diagnosis. This represents the first steps toward the
development of a single RDT-based system for the differential diagnosis of
numerous AFIs of interest.
PMID- 27490380
TI - 20(th) EuroQSAR: Understanding Chemical-Biological Interactions.
PMID- 27490381
TI - GTM-Based QSAR Models and Their Applicability Domains.
AB - In this paper we demonstrate that Generative Topographic Mapping (GTM), a machine
learning method traditionally used for data visualisation, can be efficiently
applied to QSAR modelling using probability distribution functions (PDF) computed
in the latent 2-dimensional space. Several different scenarios of the activity
assessment were considered: (i) the "activity landscape" approach based on direct
use of PDF, (ii) QSAR models involving GTM-generated on descriptors derived from
PDF, and, (iii) the k-Nearest Neighbours approach in 2D latent space.
Benchmarking calculations were performed on five different datasets: stability
constants of metal cations Ca(2+) , Gd(3+) and Lu(3+) complexes with organic
ligands in water, aqueous solubility and activity of thrombin inhibitors. It has
been shown that the performance of GTM-based regression models is similar to that
obtained with some popular machine-learning methods (random forest, k-NN, M5P
regression tree and PLS) and ISIDA fragment descriptors. By comparing GTM
activity landscapes built both on predicted and experimental activities, we may
visually assess the model's performance and identify the areas in the chemical
space corresponding to reliable predictions. The applicability domain used in
this work is based on data likelihood. Its application has significantly improved
the model performances for 4 out of 5 datasets.
PMID- 27490382
TI - Prediction of PARP Inhibition with Proteochemometric Modelling and Conformal
Prediction.
AB - Poly(ADP-ribose) polymerases (PARPs) play a key role in DNA damage repair. PARP
inhibitors act as chemo- and radio- sensitizers and thus potentiate the
cytotoxicity of DNA damaging agents. Although PARP inhibitors are currently
investigated as chemotherapeutic agents, their cross-reactivity with other
members of the PARP family remains unclear. Here, we apply Proteochemometric
Modelling (PCM) to model the activity of 181 compounds on 12 human PARPs. We
demonstrate that PCM (R0 (2) test =0.65-0.69; RMSEtest =0.95-1.01 degrees C)
displays higher performance on the test set (interpolation) than Family QSAR and
Family QSAM (Tukey's HSD, alpha 0.05), and outperforms Inductive Transfer
knowledge among targets (Tukey's HSD, alpha 0.05). We benchmark the predictive
signal of 8 amino acid and 11 full-protein sequence descriptors, obtaining that
all of them (except for SOCN) perform at the same level of statistical
significance (Tukey's HSD, alpha 0.05). The extrapolation power of PCM to new
compounds (RMSE=1.02+/-0.80 degrees C) and targets (RMSE=1.03+/-0.50 degrees C)
is comparable to interpolation, although the extrapolation ability is not uniform
across the chemical and the target space. For this reason, we also provide
confidence intervals calculated with conformal prediction. In addition, we
present the R package conformal, which permits the calculation of confidence
intervals for regression and classification caret models.
PMID- 27490383
TI - Data Mining and Machine Learning Tools for Combinatorial Material Science of All
Oxide Photovoltaic Cells.
AB - Growth in energy demands, coupled with the need for clean energy, are likely to
make solar cells an important part of future energy resources. In particular,
cells entirely made of metal oxides (MOs) have the potential to provide clean and
affordable energy if their power conversion efficiencies are improved. Such
improvements require the development of new MOs which could benefit from
combining combinatorial material sciences for producing solar cells libraries
with data mining tools to direct synthesis efforts. In this work we developed a
data mining workflow and applied it to the analysis of two recently reported
solar cell libraries based on Titanium and Copper oxides. Our results demonstrate
that QSAR models with good prediction statistics for multiple solar cells
properties could be developed and that these models highlight important factors
affecting these properties in accord with experimental findings. The resulting
models are therefore suitable for designing better solar cells.
PMID- 27490384
TI - An Ab Initio Method for Designing Multi-Target Specific Pharmacophores using
Complementary Interaction Field of Aspartic Proteases.
AB - For past few decades, key objectives of rational drug discovery have been the
designing of specific and selective ligands for target proteins. Infectious
diseases like malaria are continuously becoming resistant to traditional
medicines, which inculcates need for new approaches to design inhibitors for
antimalarial targets. A novel method for ab initio designing of multi target
specific pharmacophores using the interaction field maps of active sites of
multiple proteins has been developed to design 'specificity' pharmacophores for
aspartic proteases. The molecular interaction field grid maps of active sites of
aspartic proteases (plasmepsin II & IV from Plasmodium falciparum, plasmepsin
from Plasmodium vivax, pepsin & cathepsin D from human) are calculated and common
pharmacophoric features for favourable binding spots in active sites are
extracted in the form of cliques of graphs using inductive logic programming
(ILP). The two pharmacophore ensembles are constructed from largest common
cliques by imposing size of receptor active site (L) and domain-specific receptor
ligand information (S). The overlap of chemical space between two ensembles and
the results of virtual screening of inhibitor database with known activities show
that this method can design efficient pharmacophores with no prior ligand
information.
PMID- 27490385
TI - Molecular Docking Study on Galantamine Derivatives as Cholinesterase Inhibitors.
AB - A training set of 22 synthetic galantamine derivatives binding to
acetylcholinesterase was docked by GOLD and the protocol was optimized in terms
of scoring function, rigidity/flexibility of the binding site, presence/absence
of a water molecule inside and radius of the binding site. A moderate correlation
was found between the affinities of compounds expressed as pIC50 values and their
docking scores. The optimized docking protocol was validated by an external test
set of 11 natural galantamine derivatives and the correlation coefficient between
the docking scores and the pIC50 values was 0.800. The derived relationship was
used to analyze the interactions between galantamine derivatives and AChE.
PMID- 27490386
TI - Perspectives of Halogen Bonding Description in Scoring Functions and QSAR/QSPR:
Substituent Effects in Aromatic Core.
AB - Halogen bonding (XB) is a new promising interaction pattern in medicinal
chemistry. It has predominantly electrostatic nature - high electrostatic
potential anisotropy. However to fully unleash the potential of XB in rational
drug design fast and robust empirical methods of XB description should be
developed. Current approaches rely heavily on ab initio calculation for each
molecule studied. Thus fast prediction of electrostatic parameters for
description of XB for arbitrary organic molecules is of paramount importance to
promptly establish QSAR/QSPR, virtual screening and molecular docking pipelines
suitable for today's agile development requirements. The two most promising
approaches to describe anisotropic electrostatic models - the extra point (EP)
charge model and the multipole expansion (ME) model - were studied on their
ability (1) to describe ab initio molecular electrostatic potential (MEP) and (2)
to produce parameters that can be predicted for each molecule empirically rather
than estimated via ab initio calculations. The reference ab initio MEP was
calculated for a set of 730 substituted halobenzenes. Parameters for anisotropic
electrostatics of both empirical models (EP and ME) studied were extracted from
ab initio MEP. The Free?Wilson and Hansch type QSPR models relating XB parameters
with aromatic substituents were built and analyzed, providing the guidelines for
further development.
PMID- 27490387
TI - In silico Prediction of Aqueous Solubility: a Comparative Study of Local and
Global Predictive Models.
AB - 32 Quantitative Structure-Property Relationship (QSPR) models were constructed
for prediction of aqueous intrinsic solubility of liquid and crystalline
chemicals. Data sets contained 1022 liquid and 2615 crystalline compounds.
Multiple Linear Regression (MLR), Support Vector Machine (SVM) and Random Forest
(RF) methods were used to construct global models, and k-nearest neighbour (kNN),
Arithmetic Mean Property (AMP) and Local Regression Property (LoReP) were used to
construct local models. A set of the best QSPR models was obtained: for liquid
chemicals with RMSE (root mean square error) of prediction in the range 0.50-0.60
log unit; for crystalline chemicals 0.80-0.90 log unit. In the case of global
models the large number of descriptors makes mechanistic interpretation
difficult. The local models use only one or two descriptors, so that a medicinal
chemist working with sets of structurally-related chemicals can readily estimate
their solubility. However, construction of stable local models requires the
presence of closely related neighbours for each chemical considered. It is
probable that a consensus of global and local QSPR models will be the optimal
approach for construction of stable predictive QSPR models with mechanistic
interpretation.
PMID- 27490388
TI - In Silico Predictions of Drug - Drug Interactions Caused by CYP1A2, 2C9 and 3A4
Inhibition - a Comparative Study of Virtual Screening Performance.
AB - The cytochrome P450 (CYP) superfamily represents the major enzyme class
responsible for the metabolism of exogenous compounds. Investigation of clearance
pathways is therefore an integral part in early drug development, as any
alteration of metabolic enzymes may markedly influence the toxicological profile
and efficacy of novel compounds. In silico methods are widely applied in drug
development to complement experimental approaches. Several different tools are
available for that purpose, however, for CYP enzymes they have only been applied
retrospectively so far. Within this study, pharmacophore- and shape-based models
and a docking protocol were generated for the prediction of CYP1A2, 2C9, and 3A4
inhibition. All theoretically validated models, the validated docking workflow,
and additional external bioactivity profiling tools were applied independently
and in parallel to predict the CYP inhibition of 29 compounds from synthetic and
natural origin. After subsequent experimental assessment of the in silico
predictions, we analyzed and compared the prospective performance of all methods,
thereby defining the suitability of the applied techniques for CYP enzymes. We
observed quite substantial differences in the performances of the applied tools,
suggesting that the rational selection of that virtual screening method that
proved to perform best can largely improve the success rates when it comes to CYP
inhibition prediction.
PMID- 27490390
TI - Peptide Binding Prediction to Five Most Frequent HLA-DQ Proteins - a
Proteochemometric Approach.
AB - Major histocompatibility complex (MHC) proteins class II, are glycoproteins
binding within the cell to short peptides with foreign origin, called epitopes,
and present them at the cell surface for inspection by T-cells. Apart from
presenting foreign antigens, they are able to present also common self-antigens
and trigger autoimmune diseases as coeliac disease and diabetes mellitus type 1.
The MHC proteins are extremely polymorphic. The polymorphism is located mainly in
the peptide binding site. In the present study, we apply a proteochemometric
approach to derive a model for prediction of peptide binding to human MHC class
II proteins from locus HLA-DQ. Proteochemometrics was applied on 2624 peptides
binding to five most frequent HLA-DQ proteins. The sequences of peptides and
proteins were described by three z-descriptors relating to hydrophobicity, steric
effects and polarity of amino acids. Cross-terms accounting for the protein
peptide interactions also were included. The derived model was validated by
external test set of 660 peptides and showed rpred (2) =0.808, AUC=0.965, 92.5 %
accuracy at threshold of pIC50 =5.3 and average sensitivity of 83 % among the top
10 % best predicted nonamers. The model is implemented in the server for MHC
binding prediction EpiTOP and is freely available at http://www.ddg
pharmfac.net/epitop.
PMID- 27490389
TI - Pharmacophore-Based Virtual Screening to Discover New Active Compounds for Human
Choline Kinase alpha1.
AB - Choline kinase (CK) catalyses the transfer of the ATP gamma-phosphate to choline
to generate phosphocholine and ADP in the presence of magnesium leading to the
synthesis of phosphatidylcholine. Of the three isoforms of CK described in
humans, only the alpha isoforms (HsCKalpha) are strongly associated with cancer
and have been validated as drug targets to treat this disease. Over the years, a
large number of Hemicholinium-3 (HC-3)-based HsCKalpha biscationic inhibitors
have been developed though the relevant common features important for the
biological function have not been defined. Here, selecting a large number of
previous HC-3-based inhibitors, we discover through computational studies a
pharmacophore model formed by five moieties that are included in the 1-benzyl-4
(N-methylaniline)pyridinium fragment. Using a pharmacophore-guided virtual
screening, we then identified 6 molecules that showed binding affinities in the
low MUM range to HsCKalpha1. Finally, protein crystallization studies suggested
that one of these molecules is bound to the choline and ATP-binding sites. In
conclusion, we have developed a pharmacophore model that not only allowed us to
dissect the structural important features of the previous HC-3 derivatives, but
also enabled the identification of novel chemical tools with good ligand
efficiencies to investigate the biological functions of HsCKalpha1.
PMID- 27490391
TI - Integrative Modeling Strategies for Predicting Drug Toxicities at the eTOX
Project.
AB - Early prediction of safety issues in drug development is at the same time highly
desirable and highly challenging. Recent advances emphasize the importance of
understanding the whole chain of causal events leading to observable toxic
outcomes. Here we describe an integrative modeling strategy based on these ideas
that guided the design of eTOXsys, the prediction system used by the eTOX
project. Essentially, eTOXsys consists of a central server that marshals requests
to a collection of independent prediction models and offers a single user
interface to the whole system. Every of such model lives in a self-contained
virtual machine easy to maintain and install. All models produce toxicity
relevant predictions on their own but the results of some can be further
integrated and upgrade its scale, yielding in vivo toxicity predictions.
Technical aspects related with model implementation, maintenance and
documentation are also discussed here. Finally, the kind of models currently
implemented in eTOXsys is illustrated presenting three example models making use
of diverse methodology (3D-QSAR and decision trees, Molecular Dynamics
simulations and Linear Interaction Energy theory, and fingerprint-based QSAR).
PMID- 27490392
TI - Virtual Screening for HIV Protease Inhibitors Using a Novel Database Filtering
Procedure.
AB - A virtual screening to find novel inhibitors for HIV protease was performed on
the ZINC database.1 A critical part in virtual screening and associated
techniques is preliminary database filtering and size reduction and for that
purpose a novel feature matrix matching procedure was used. The reduction of ~14
million available ligands to a subset of 14299 ligands was achieved with a
structure based approach where the analysis of the 3D structure of the active
site of the protease produced a graph with hydrogen bond donor, hydrogen bond
acceptor and hydrophobic subsites represented as graph nodes. A similar treatment
was also applied to the compound database content and the comparison of binding
site and ligand graphs was used to preselect potentially active ligands. The
resulting set was further subjected to docking. The algorithm used was able to
find several novel as well as previously known and experimentally tested ligands,
demonstrating the validity of the approach.
PMID- 27490393
TI - The Permeability of an Artificial Membrane for Wide Range of pH in Human
Gastrointestinal Tract: Experimental Measurements and Quantitative
Structure?Activity Relationship.
AB - In silico models for membrane permeability have been based on values measured for
single pH. Depending on the diet (fasted/fed state) and part of human intestine
the range of pH varies approximately from 2.4 to 8.0. This motivated to study and
model the membrane permeability of chemicals considering the whole range of pH in
the human intestine. For this, effective membrane permeability values were
measured for 65 drugs and drug-like compounds using PAMPA method at four pHs (3,
5, 7.4, 9) over 48 h, introducing technological innovations for the time
dependence measurement. The highest permeability value of a compound from four
pHs was used to derive QSAR analyzing a large pool of molecular descriptors and
introducing new descriptor. Using stepwise forward selection approach a
significant QSAR model was derived that included only two mechanistically
relevant descriptors, the logarithmic octanol-water partition coefficient and
hydrogen bonding surface area. Prediction confidence of the model was blind
tested with a true external validation set of 15 compounds. The resulting QSAR
model shows potential to combine permeability values from various pH-s into one
descriptive and predictive model for estimating maximum permeability in human
gastrointestinal tract. The QSAR model and data are available through the QsarDB
repository (http://dx.doi.org/10.15152/QDB.137).
PMID- 27490395
TI - Welcome to JBJS Reviews!
PMID- 27490396
TI - Allografts in Foot and Ankle Surgery: A Critical Analysis Review.
PMID- 27490394
TI - Compounds Derived from the Bhutanese Daisy, Ajania nubigena, Demonstrate Dual
Anthelmintic Activity against Schistosoma mansoni and Trichuris muris.
AB - BACKGROUND: Whipworms and blood flukes combined infect almost one billion people
in developing countries. Only a handful of anthelmintic drugs are currently
available to treat these infections effectively; there is therefore an urgent
need for new generations of anthelmintic compounds. Medicinal plants have
presented as a viable source of new parasiticides. Ajania nubigena, the Bhutanese
daisy, has been used in Bhutanese traditional medicine for treating various
diseases and our previous studies revealed that small molecules from this plant
have antimalarial properties. Encouraged by these findings, we screened four
major compounds isolated from A. nubigena for their anthelmintic properties.
METHODOLOGY/PRINCIPAL FINDINGS: Here we studied four major compounds derived from
A. nubigena for their anthelmintic properties against the nematode whipworm
Trichuris muris and the platyhelminth blood fluke Schistosoma mansoni using the
xWORM assay technique. Of four compounds tested, two compounds-luteolin (3) and
(3R,6R)-linalool oxide acetate (1)-showed dual anthelmintic activity against S.
mansoni (IC50 range = 5.8-36.9 MUg/mL) and T. muris (IC50 range = 9.7-20.4
MUg/mL). Using scanning electron microscopy, we determined luteolin as the most
efficacious compound against both parasites and additionally was found effective
against the schistosomula, the infective stage of S. mansoni (IC50 = 13.3
MUg/mL). Luteolin induced tegumental damage to S. mansoni and affected the
cuticle, bacillary bands and bacillary glands of T. muris. Our in vivo assessment
of luteolin (3) against T. muris infection at a single oral dosing of 100 mg/kg,
despite being significantly (27.6%) better than the untreated control group, was
markedly weaker than mebendazole (93.1%) in reducing the worm burden in mice.
CONCLUSIONS/SIGNIFICANCE: Among the four compounds tested, luteolin demonstrated
the best broad-spectrum activity against two different helminths-T. muris and S.
mansoni-and was effective against juvenile schistosomes, the stage that is
refractory to the current gold standard drug, praziquantel. Medicinal chemistry
optimisation including cytotoxicity analysis, analogue development and structure
activity relationship studies are warranted and could lead to the identification
of more potent chemical entities for the control of parasitic helminths of humans
and animals.
PMID- 27490397
TI - Measuring Value in Orthopaedic Surgery.
PMID- 27490398
TI - Pitfalls, Errors, and Unintended Consequences in Musculoskeletal Oncology: How
They Occur and How They Can Be Avoided.
PMID- 27490399
TI - Diagnosis of Periprosthetic Infection After Shoulder Arthroplasty: A Critical
Analysis Review.
PMID- 27490400
TI - The decrease of consistence probability: at the crossroad of catastrophic
transition of a biological system.
AB - BACKGROUND: Unlike traditional detection of a disease state in which there are
clear phenomena, it is usually a challenge to identify the pre-disease state
during the progression of a complex disease just before the serious
deterioration, not only because of the high complexity of the biological system,
but there may be few clues and apparent changes appearing until the catastrophic
critical transition occurs. RESULTS: In this work, by exploiting the different
dynamical features between the normal and pre-disease states, we present a hidden
Markov-model (HMM) based computational method to identify the pre-disease state
and elucidate the essential mechanisms during the critical transition at the
network level. Specifically, by considering the network variation and regarding
that the pre-disease state is the end or shift-point of a stationary Markov
process, a consistence score is proposed to measure the probability that a system
is in consistency with the normal state. As validation, this approach is applied
to detect the upcoming critical transition of complex systems based on both the
dataset generated from a simulated network and the rich information provided by
high-throughput microarray data. The effectiveness of our method has been
demonstrated by the identification of the pre-disease states for two real
datasets including HCV-induced hepatocellular carcinoma and virus-induced
influenza infection. CONCLUSION: From dynamical view point, the critical
transition phenomena in many biological processes are of some generic properties,
which can be detected by the established method.
PMID- 27490401
TI - Understanding Diffusion in Hierarchical Zeolites with House-of-Cards Nanosheets.
AB - Introducing mesoporosity to conventional microporous sorbents or catalysts is
often proposed as a solution to enhance their mass transport rates. Here, we show
that diffusion in these hierarchical materials is more complex and exhibits non
monotonic dependence on sorbate loading. Our atomistic simulations of n-hexane in
a model system containing microporous nanosheets and mesopore channels indicate
that diffusivity can be smaller than in a conventional zeolite with the same
micropore structure, and this observation holds true even if we confine the
analysis to molecules completely inside the microporous nanosheets. Only at high
sorbate loadings or elevated temperatures, when the mesopores begin to be
sufficiently populated, does the overall diffusion in the hierarchical material
exceed that in conventional microporous zeolites. Our model system is free of
structural defects, such as pore blocking or surface disorder, that are typically
invoked to explain slower-than-expected diffusion phenomena in experimental
measurements. Examination of free energy profiles and visualization of molecular
diffusion pathways demonstrates that the large free energy cost (mostly enthalpic
in origin) for escaping from the microporous region into the mesopores leads to
more tortuous diffusion paths and causes this unusual transport behavior in
hierarchical nanoporous materials. This knowledge allows us to re-examine zero
length-column chromatography data and show that these experimental measurements
are consistent with the simulation data when the crystallite size instead of the
nanosheet thickness is used for the nominal diffusional length.
PMID- 27490403
TI - Mimickers of Cervical Radiculopathy.
PMID- 27490402
TI - New laparoscopic approach to the pudendal nerve for neuromodulation based on an
anatomic study.
AB - AIMS: The aim was to develop a new laparoscopic technique for placement of a
pudendal lead. METHODS: Development of a direct, feasible and reliable minimal
invasive laparoscopic approach to the pudendal nerve (PN). Thirty-one embalmed
human specimens were dissected for the relevant anatomic structures of the
pelvis. Step-by-step documentation and analysis of the laparoscopic approach in
order to locate the PN directly in its course around the medial part of the
sacrospinous ligament and test this approach for feasibility. Landmarks for
intraoperative navigation towards the PN as well as the possible position of an
lead were selected and demonstrated. RESULTS: The visible medial umbilical fold,
the intrapelvine part of the internal pudendal artery, the coccygeus muscle and
the sacrospinous ligament are the main landmarks. The PN traverses the medial
part of the sacrospinous ligament dorsally, medially to the internal pudendal
artery. The medial part of the sacrospinous ligament has to be exposed in order
to display the nerve. An lead can be placed ventrally on the nerve or around it,
depending on the lead type or shape. CONCLUSIONS: A precise and reliable
identification of the PN by means of laparoscopy is feasible with an easy four
step approach: (1) identification of the medial umbilical fold; (2)
identification of the internal iliac artery; (3) identification of the internal
pudendal artery and incision of the coccygeus muscle ('white line', arcuated
line); and (4) exposition of the medial part of the sacrospinous ligament to
display the PN.
PMID- 27490404
TI - Elbow Injuries in the Throwing Athlete.
PMID- 27490405
TI - The Evaluation and Treatment of Polyostotic Lesions.
PMID- 27490406
TI - Orthopaedic Graduate Medical Education: A Changing Paradigm.
PMID- 27490407
TI - QuickStats: Percentage* of Preterm Births(?) Among Teens Aged 15-19 Years, by
Race/Ethnicity - National Vital Statistics System, United States, 2007-2014(S).
AB - During 2007-2014, the percentage of births among teens aged 15-19 years that were
preterm declined for each racial/ethnic group, except for non-Hispanic Asian or
Pacific Islander teens, where the change was not significant. In 2014, the
percentage of births that were preterm was higher among non-Hispanic black and
non-Hispanic Asian or Pacific Islander teens (10.6% for both) than non-Hispanic
white (8.6%), non-Hispanic American Indian or Alaska Native (8.2%), and Hispanic
(7.9%) teens.
PMID- 27490408
TI - "Quitting like a Turk:" How political priority developed for tobacco control in
Turkey.
AB - In recent years, tobacco control emerged as a political priority in Turkey and
today the country is widely regarded as one of the global leaders in tackling
tobacco use. Although political priority is considered a facilitating factor to
the success of addressing public health issues, there is a paucity of research to
help us understand how it is developed in middle-income countries. The primary
aim of this study is to understand the process and determinants of how tobacco
control became a political priority in Turkey using the Multiple Streams
Framework. A mixed-methods case study approach was used whereby data were
gathered from three different sources: in-depth interviews (N = 19), document
reviews (N = 216), and online self-administered surveys (N = 61). Qualitative
data were collected for the purpose of understanding the processes and
determinants that led to political prioritization of tobacco control and were
analyzed using deductive and inductive coding. Quantitative data were collected
to examine the actors and were analyzed using descriptive statistics and network
nominations. Data were triangulated. Findings revealed that tobacco control
achieved political priority in Turkey as a result of the development and
convergence of multiple streams, including a fourth, separate global stream.
Findings also shed light on the importance of Turkey's foreign policy in the
transformation of the political stream. The country's desire for European Union
accession and global visibility helped generate a political environment that was
receptive to global norms for tobacco control. A diverse but cohesive network of
actors joined forces with global allies to capitalize on this opportunity.
Results suggest (1) the importance of global-agenda setting activities on
political priority development, (2) the utility of aligning public health and
foreign policy goals and (3) the need to build a strong global incentive
structure to help entice governments to take action on public health issues.
PMID- 27490410
TI - Islet Transplantation Provides Superior Glycemic Control With Less Hypoglycemia
Compared With Continuous Subcutaneous Insulin Infusion or Multiple Daily Insulin
Injections.
AB - BACKGROUND: The aim was to compare efficacy of multiple daily injections (MDI),
continuous subcutaneous insulin infusion (CSII) and islet transplantation to
reduce hypoglycemia and glycemic variability in type 1 diabetes subjects with
severe hypoglycemia. METHODS: This was a within-subject, paired comparison of MDI
and CSII and CSII with 12 months postislet transplantation in 10 type 1 diabetes
subjects referred with severe hypoglycemia, suitable for islet transplantation.
Individuals were assessed with HbA1c, Edmonton Hypoglycemia Score (HYPOscore),
continuous glucose monitoring (CGM) and in 8 subjects measurements of glucose
variability using standard deviation of glucose (SD glucose) from CGM and
continuous overlapping net glycemic action using a 4 hour interval (CONGA4).
RESULTS: After changing from MDI to CSII before transplantation, 10 subjects
reduced median HYPOscore from 2028 to 1085 (P < 0.05) and hypoglycemia events
from 24 to 8 per patient-year (P < 0.05). While HbA1c, mean glucose and median
percent time hypoglycemic on CGM were unchanged with CSII, SD glucose and CONGA4
reduced significantly (P < 0.05). At 12 months posttransplant 9 of 10 were C
peptide positive, (5 insulin independent). Twelve months postislet
transplantation, there were significant reductions in all baseline parameters
versus CSII, respectively, HbA1c (6.4% cf 8.2%), median HYPOscore (0 cf 1085),
mean glucose (7.1 cf 8.6 mmol L), SD glucose (1.7 cf 3.2 mmol/L), and CONGA4 (1.6
cf 3.0). CONCLUSIONS: In subjects with severe hypoglycemia suitable for islet
transplantation, CSII decreased hypoglycemia frequency and glycemic variability
compared with MDI whereas islet transplantation resolved hypoglycemia and further
improved glycemic variability regardless of insulin independence.
PMID- 27490411
TI - Predicting Outcomes on the Liver Transplant Waiting List in the United States:
Accounting for Large Regional Variation in Organ Availability and Priority
Allocation Points.
AB - BACKGROUND: The probability of liver transplant and death on the waiting list in
the United States varies greatly by donation service area (DSA) due to geographic
differences in availability of organs and allocation of priority points, making
it difficult for providers to predict likely outcomes after listing. We aimed to
develop an online calculator to report outcomes by region and patient
characteristics. METHODS: Using the Scientific Registry of Transplant Recipients
database, we included all prevalent US adults aged 18 years or older waitlisted
for liver transplant, examined on 24 days at least 30 days apart over a 2-year
period. Outcomes were determined at intervals of 30 to 365 days. Outcomes are
reported by transplant program, DSA, region, and the nation for comparison, and
can be shown by allocation or by laboratory model for end-stage liver disease
(MELD) score (6-14, 15-24, 25-29, 30-34, 35-40), age, and blood type. RESULTS:
Outcomes varied greatly by DSA; for candidates with allocation MELD 25-29, the
25th and 75th percentiles of liver transplant probability were 30% and 67%,
respectively, at 90 days. Corresponding percentiles for death or becoming too
sick to undergo transplant were 5% and 9%. Outcomes also varied greatly for
candidates with and without MELD exception points. CONCLUSIONS: The waitlist
outcome calculator highlights ongoing disparities in access to liver transplant
and may assist providers in understanding and counseling their patients about
likely outcomes on the waiting list.
PMID- 27490412
TI - Successful Renal Transplantation of Deceased Donor Kidneys With 100% Glomerular
Fibrin Thrombi and Acute Renal Failure Due to Disseminated Intravascular
Coagulation.
AB - BACKGROUND: Disseminated intravascular coagulation (DIC)-positive kidneys have
historically been turned down for fear of poor outcomes. Higher severity
injuries, which are prone to DIC, are typically seen in younger, otherwise
healthy potential donors. The continued kidney allograft shortage has generated
interest in the use of these DIC-positive grafts. There have been some reports of
acceptable outcomes of renal transplantation using kidneys from donors with DIC.
There are multiple clinical series demonstrating good outcomes from DIC-positive
kidneys when the extent of glomeruli containing fibrin thrombi is less than 50%
and donor renal function is preserved. These grafts are frequently associated
with a period of delayed graft function. METHODS: We report 2 transplants with
kidneys from brain dead donors with known DIC. RESULTS: Both donors had renal
failure and pretransplant renal biopsies showing 100% of the glomeruli containing
fibrin thrombi. The recipients experienced delayed graft function requiring
hemodialysis which was discontinued on postoperative days 18 and 39 for cases 1
and 2, respectively. Both patients are now over 14 months posttransplant with
stable allograft function. CONCLUSIONS: Until clearer organ selection criteria
are established, caution should be exercised when considering the use of kidneys
with a similar phenotype and allocation decisions made by a multidisciplinary
transplant team on a case-by-case basis.
PMID- 27490409
TI - Impact of Immune-Modulatory Drugs on Regulatory T Cell.
AB - Immunosuppression strategies that selectively inhibit effector T cells while
preserving and even enhancing CD4FOXP3 regulatory T cells (Treg) permit immune
self-regulation and may allow minimization of immunosuppression and associated
toxicities. Many immunosuppressive drugs were developed before the identity and
function of Treg were appreciated. A good understanding of the interactions
between Treg and immunosuppressive agents will be valuable to the effective
design of more tolerable immunosuppression regimens. This review will discuss
preclinical and clinical evidence regarding the influence of current and emerging
immunosuppressive drugs on Treg homeostasis, stability, and function as a
guideline for the selection and development of Treg-friendly immunosuppressive
regimens.
PMID- 27490413
TI - Clinical and Economic Consequences of Early Cancer After Kidney Transplantation
in Contemporary Practice.
AB - BACKGROUND: Current clinical and economic consequences of cancer after kidney
transplantation are incompletely defined. METHODS: We examined United States
Renal Data System records of Medicare-insured kidney transplant recipients in
2000 to 2011 to determine clinical and economic impacts of cancer diagnosed
within the first 3 years posttransplantation. Cancer diagnoses were identified
using Medicare billing codes and categorized as nonmelanoma skin cancer (NMSC),
viral-linked and "other" cancers. Associations of cancers with mortality and
graft loss were estimated by time-varying Cox regression. Impacts of cancer
diagnoses on inpatient and outpatient costs within each year were quantified by
multivariate linear regression modeling. RESULTS: Among 67 157 recipients, by 3
years posttransplant, NMSC was diagnosed in 5.7%, viral-linked cancer in 1.9%,
and "other" cancers in 6.3%. Viral-linked cancer was associated with more than 3
fold increased risk in subsequent mortality until the third transplant
anniversary, and nearly twice the mortality risk after year 3. "Other" cancers
had similar associations with death and graft loss, whereas NMSC was associated
with 33% higher mortality beyond the third year posttransplant. Viral-linked
cancer had the largest inpatient and outpatient cost impacts per case, followed
by "other" cancer, whereas NMSC impacted only outpatient costs. Care of new
cancer diagnoses was generally more costly than care of previously established
diagnoses. Cancer accounted for 3% to 5.5% of total inpatient Medicare
expenditures and 1.5% to 3.3% of outpatient expenditures in the first 3 years
posttransplant. CONCLUSIONS: Early posttransplant malignancy is an expensive and
morbid condition that warrants attention in efforts to improve pretransplant
screening and management protocols before and after transplant.
PMID- 27490414
TI - Utility of Applying Quality Assessment Tools for Kidneys With KDPI >=80.
AB - BACKGROUND: Kidneys with "high" Kidney Donor Profile Index (KDPI) are often
biopsied and pumped, yet frequently discarded. METHODS: In this multicenter
study, we describe the characteristics and outcomes of kidneys with KDPI of 80 or
greater that were procured from 338 deceased donors. We excluded donors with
anatomical kidney abnormalities. RESULTS: Donors were categorized by the number
of kidneys discarded: (1) none (n = 154, 46%), (2) 1 discarded and 1 transplanted
(n = 48, 14%), (3) both discarded (n = 136, 40%). Donors in group 3 were older,
more often white, and had higher terminal creatinine and KDPI than group 1 (all P
< 0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard
was associated with biopsy findings and first hour renal resistance. Kidney
injury biomarker levels (neutrophil gelatinase-associated lipocalin, IL-18, and
kidney injury molecule-1 measured from donor urine at procurement and from
perfusate soon after pump perfusion) were not different between groups. There was
no significant difference in 1-year estimated glomerular filtration rate or graft
failure between groups 1 and 2 (41.5 +/- 18 vs 41.4 +/- 22 mL/min per 1.73 m; P =
0.97 and 9% vs 10%; P = 0.76). CONCLUSIONS: Kidneys with KDPI of 80 or greater
comprise the most resource consuming fraction of our donor kidney pool and have
the highest rates of discard. Our data suggest that some discarded kidneys with
KDPI of 80 or greater are viable; however, current tools and urine and perfusate
biomarkers to identify these viable kidneys are not satisfactory. We need better
methods to assess viability of kidneys with high KDPI.
PMID- 27490417
TI - Prevalence and Clinical Impact of Donor-Specific Alloantibody Among Intestinal
Transplant Recipients.
AB - BACKGROUND: Rejection remains the leading cause of allograft loss, and a major
barrier to improving long-term outcomes after intestinal transplantation. Our aim
is to define the prevalence and investigate the role of donor-specific antibody
(DSA) on intestinal graft outcomes. METHODS: The study includes 109 transplants
performed in 95 recipients at a single center. Patients were screened for DSA
pretransplant, monitored regularly posttransplant and when clinically indicated
using the single-antigen bead Luminex assay. Standard induction immunosuppression
was with interleukin-2 receptor antagonists, and antithymocyte globulin in high
risk recipients. Maintenance regimens were tacrolimus-based. RESULTS:
Pretransplant DSA was detected in 12 (11%) recipients with 50% continuing to have
circulating antibodies posttransplant. An additional 24 (25%) patients developed
de novo DSA, and of these, 71% had persistent antibodies. Recipients with
preformed DSA demonstrated elevated risks of early graft failure, whereas those
with de novo DSA experienced accelerated graft loss once DSA was detected,
reaching a 28% failure rate within 2 years. HLA-DQ mismatch is a significant risk
factor for de novo DSA emergence, whereas the persistence of antibodies is
predicted by DSA strength and specificity. Although inclusion of the liver in the
intestinal allograft imparts an immunological advantage against rejection-related
graft loss, this protective effect was lost among recipients with persistent DSA.
CONCLUSIONS: The presence of DSA is associated with inferior graft outcomes among
intestinal transplant recipients. An enhanced understanding of the mechanisms by
which DSA causes allograft injury, and effective strategies targeting humoral
immune reactivity are needed to improve long-term intestinal graft outcomes.
PMID- 27490416
TI - Proangiogenic Function of T Cells in Corneal Transplantation.
AB - BACKGROUND: Corneal neovascularization increases the risk of T cell-mediated
allograft rejection. Here, we investigate whether T cells promote angiogenesis in
transplantation. METHODS: Conventional effector T cells were collected from
draining lymph nodes of allogeneic or syngeneic corneal transplanted BALB/c mice.
T cells were either cocultured with vascular endothelial cells (VECs) to assess
VEC proliferation or used in a mixed lymphocyte reaction assay. Messenger RNA
(mRNA) expression of vascular endothelial growth factor (VEGF)-A, -C, and VEGF
receptor 2 (VEGF-R2) in VECs was assessed by real-time PCR. VEGF-A protein
expression was determined by enzyme-linked immunosorbent assay. Flow cytometry
was used to analyze VEGF-R2 expression in corneal CD31 cells, and VEGF-A and
IFNgamma expression in corneal CD4 T cells. RESULTS: Allogeneic T cells from high
risk (HR) grafted mice induced more VEC proliferation than those from syngeneic
transplant recipients (P = 0.03). Vascular endothelial growth factor-A mRNA and
protein expression were higher in T cells from draining lymph nodes (P = 0.03 and
P = 0.04, respectively) and cornea (protein; P = 0.04) of HR compared with low
risk (LR) grafted hosts. Vascular endothelial growth factor-A, VEGF-C, and VEGF
R2 mRNA expression were increased in VECs when cocultured with T cells from HR
transplants compared with LR transplants and naive mice. In addition, IFNgamma
blockade in T cell/VEC coculture increased VEC proliferation and VEGF-A protein
expression, whereas blocking VEGF-A significantly reduced VEC proliferation (P =
0.04). CONCLUSIONS: Allogeneic T cells from corneal transplant hosts promote VEC
proliferation, probably via VEGF-A signaling, whereas IFNgamma shows an
antiangiogenic effect. Our data suggest that T cells are critical mediators of
angiogenesis in transplantation.
PMID- 27490418
TI - Wound Healing Complications in Kidney Transplant Recipients Receiving Everolimus.
AB - BACKGROUND: De novo use of mammalian target of rapamycin inhibitors after kidney
transplantation is associated with a concentration-dependent incidence of wound
healing adverse events (WHAE). The objective of this analysis was to compare the
incidence of WHAE in patients receiving everolimus (EVR) or mycophenolate sodium
(MPS). METHODS: This was a predefined subanalysis of a single-center prospective
randomized study in which 288 kidney transplant recipients receiving tacrolimus
and prednisone were randomized for 3 different regimens: rabbit antithymocyte
globulin (r-ATG)/EVR (N = 85); basiliximab (BAS)/EVR (N = 102); BAS/MPS (N =
101). Clinical WHAE were prospectively collected using a prespecified case report
form in all study visits. Abdominal ultrasound was performed at 30 days
posttransplant to capture subclinical abnormalities. Surgeons were blinded to
randomized treatment and no specific surgical procedures were implemented.
RESULTS: A higher proportion of patients in BAS/EVR showed at least 1 clinical
WHAE (22.3% vs 35.3% vs 22.0%, P = 0.03) and total clinical and subclinical WHAE
(35% vs 42% vs 26%, P = 0.014) compared with BAS/MPS, respectively. A higher
proportion of patients in r-ATG/EVR showed subclinical WHAE (13% vs 7% vs 4%, P =
0.025) compared with BAS/MPS, respectively. Patients receiving EVR showed a
higher risk of developing clinical or subclinical WHAE (r-ATG/EVR vs BAS/MPS
hazard ratio 1.30; BAS/EVR vs BAS/MPS hazard ratio 1.73, P = 0.028). CONCLUSIONS:
In this cohort of de novo kidney transplant recipients receiving tacrolimus and
prednisone, the use of EVR was associated with higher incidence of combined
clinical and subclinical WHAE compared with MPS.
PMID- 27490419
TI - Increased Risk of Death for Patients on the Waitlist for Liver Transplant
Residing at Greater Distance From Specialized Liver Transplant Centers in the
United States.
AB - BACKGROUND: We have previously shown that patients listed for orthotopic liver
transplantation (OLT) in United Network for Organ Sharing Region 4 (Texas and
Oklahoma) have higher waitlist mortality rates when residing more than 30 miles
from specialized liver transplant centers (LTC). Considering that findings might
only be exclusive for this region with its peculiarities in terms of having the
highest land surface extensions, lowest population densities, and largest rural
populations. We investigated the entire OLT patient population in the United
States to assess if our previous regional findings are nationally validated and
if a rural, micropolitan, or metropolitan residence location affects outcome of
waitlisted OLT patients in the nation. METHODS: Patients waiting for OLT in the
United States from 2002 to 2012 were stratified by distance from the patients'
residence to LTC and by Rural Urban Commuting Area (RUCA) codes classification.
Statistical analyses were performed to evaluate risk of mortality on the waitlist
and the likelihood to receive an OLT using a Cox proportional hazards model and a
generalized additive model with a logistic link. RESULTS: Survival time and
probability of death while on the waitlist for OLT using distance to LTC showed
significant increased risk with the distance (P = 0.001 and P < 0.0001,
respectively). At the same time, using RUCA classification as the variable did
not show significance (P = 0.14 and P = 0.73, respectively). CONCLUSIONS:
Distance from an LTC is a risk factor of mortality on the waitlist for OLT,
whereas RUCA classification is not a significant factor.
PMID- 27490420
TI - Owning Up to Negative Ingroup Traits: How Personal Autonomy Promotes the
Integration of Group Identity.
AB - OBJECTIVE: Our experiences, attributes, and behaviors are diverse, inconsistent,
and often negative. Consequently, our capacity to assimilate divergent
experiences-particularly negative aspects-is important to the development of a
unified self. Whereas this process of integration has received attention at the
level of personal identity, it has not been assessed at the level of group
identity. OBJECTIVE: We examined the mechanisms involved in integrating positive
and negative ingroup identities, as well as related outcomes. METHOD: In three
experiments, participants (N = 332) high and low in autonomy identified either
positive or negative aspects of their ingroup and then indicated the extent to
which they integrated the attribute. RESULTS: Those high in personal autonomy
integrated both positive and negative identities, whereas those low in autonomy
acknowledged only positive identities. Study 2 showed that, regardless of
identity valence, those high in autonomy felt satisfied and close with their
group. Conversely, those low in autonomy felt less close and more dissatisfied
with their group after reflecting on negative identities. Finally, reflecting on
a negative identity reduced prejudice, but only for those high in autonomy.
CONCLUSIONS: Owning up to negative group traits is facilitated by autonomy and
demonstrates benefits for ingroup and intergroup processes.
PMID- 27490421
TI - Perception of occlusion by young infants: Must the occlusion event be congruent
with the occluder?
AB - Four-month-old infants perceive continuity of an object's trajectory through
occlusion, even when the occluder is illusory, and several cues are apparently
needed for young infants to perceive a veridical occlusion event. In this paper
we investigated the effects of dislocating the spatial relation between the
occlusion events and the visible edges of the occluder. In two experiments
testing 60 participants, we demonstrated that 4-month-olds do not perceive
continuity of an object's trajectory across an occlusion if the deletion and
accretion events are spatially displaced relative to the occluder edges
(Experiment 1) or if deletion and accretion occur along a linear boundary that is
incorrectly oriented relative to the occluder's edges (Experiment 2). Thus
congruence of these cues is apparently important for perception of veridical
occlusion. These results are discussed in relation to an account of the
development of perception of occlusion and object persistence.
PMID- 27490422
TI - Ion Dynamics in a Mixed-Cation Alkoxy-Ammonium Ionic Liquid Electrolyte for
Sodium Device Applications.
AB - The ion dynamics in a novel sodium-containing room-temperature ionic liquid (IL)
consisting of an ether-functionalised quaternary ammonium cation and
bis(trifluoromethylsulfonyl)amide [NTf2 ] anion with various concentrations of
Na[NTf2 ] have been characterised using differential scanning calorimetry,
impedance spectroscopy, diffusometry and NMR relaxation measurements. The IL
studied has been specifically designed to dissolve a relatively large
concentration of Na[NTf2 ] salt (over 2 mol kg-1 ) as this has been shown to
improve ion transport and conductivity. Consistent with other studies, the
measured ionic conductivity and diffusion coefficients show that the overall
ionic mobility decreases with decreasing temperature and increasing salt content.
NMR relaxation measurements provide evidence for correlated dynamics between the
ether-functionalised ammonium and Na cations, possibly with the latter species
acting as cross-links between multiple ammonium cations. Finally, preliminary
cyclic voltammetry experiments show that this IL can undergo stable
electrochemical cycling and could therefore be potentially useful as an
electrolyte in a Na-based device.
PMID- 27490423
TI - Editorial Comment.
PMID- 27490424
TI - Reply by Authors.
PMID- 27490425
TI - Perioperative Hearing Evaluations for Patients Undergoing Tympanostomy Tube
Placement.
AB - Importance: Obtaining hearing thresholds is an important step in the evaluation
of a child with otitis media because decreased hearing in the presence of a
chronic middle ear effusion factors into the decision to place tympanostomy tubes
(TTs). Objective: To provide evidence regarding appropriate use of perioperative
hearing evaluations in conjunction with TTs. Design, Setting, and Participants:
Case series with medical record review of all patients aged 0 to 24 years who
received TTs at a tertiary pediatric care facility from June 1, 2010, through
June 1, 2011. Medical records were abstracted by 1 researcher for surgical,
audiometric, tympanometric, clinical, and patient demographic data. The data
analysis was performed between December 1, 2014, and June 1, 2015. Main Outcomes
and Measures: Audiometric data were examined to determine the number of patients
with hearing loss preoperatively and postoperatively, with the intention to
describe the population with no prior hypothesis regarding results. Results: Of
2274 patients identified, 910 (40.0%) were female. Median (interquartile range)
age at TT placement was 2.62 (1.48-4.94) years. A total of 1757 (77.3%) underwent
audiometric evaluation preoperatively, 1742 (76.6%) postoperatively, and 1395
(61.3%) both preoperatively and postoperatively; 170 (7.5%) had no audiometric
testing. Within 1 year after surgery, 271 (11.9%) of patients had evidence of
nonfunctional tubes. Postoperatively, 19.9% (347 of the 1742 patients who
received a postoperative evaluation) had hearing loss. In all, 89 (3.9%) patients
had a permanent sensorineural hearing loss, and 15 (0.66%) had a persistent
conductive hearing loss. Conclusions and Relevance: A postoperative audiometric
examination should be performed in children who have hearing loss when evaluated
before TT placement to determine whether resolution of the hearing loss was
obtained.
PMID- 27490426
TI - Understanding spinal cord compression.
PMID- 27490429
TI - How to encourage trial reporting.
PMID- 27490427
TI - Prevalence of Sleep-Disordered Breathing and Patient Characteristics in a
Coronary Artery Disease Cohort Undergoing Cardiovascular Rehabilitation.
AB - PURPOSE: Coronary artery disease (CAD) is a leading cause of death and
identification of risk factors for CAD is crucial. One such potential risk factor
is sleep-disordered breathing (SDB). This prospective cohort study investigated
the prevalence of SDB and determined risk factors for the presence of SDB in a
large CAD cohort undergoing cardiac rehabilitation. METHODS: A total of 1425
patients with confirmed CAD starting rehabilitation were screened for SDB using
cardiorespiratory polygraphy (n = 921) or polygraphy plus pulse oximetry (n =
484). RESULTS: A total of 1408 patients were included; 69.5% were male, 78% had
acute coronary syndrome, and 22% had stable CAD. The prevalence of SDB (apnea
hypopnea index [AHI] >=5/h) was 83%. Moderate to severe SDB (AHI >=15/h) was
present in 53%. Up to 70% of coronary artery bypass graft (CABG) recipients had
an AHI >=15/h versus 33% of those who had not undergone CABG. SDB severity did
not vary significantly in patients with stable CAD or on the basis of left
ventricular ejection fraction. SDB was more severe and the frequency of oxygen
desaturation was higher in men than in women. Multivariate logistic regression
identified age, sex, body mass index, and CABG as independent risk factors for
severe SDB. CONCLUSION: SDB is a highly prevalent comorbidity in patients with
CAD, particularly those who have undergone CABG. These results strengthen
existing associations and emphasize the importance of diagnosing and monitoring
SDB in patients with CAD entering a cardiac rehabilitation program. Early
diagnosis and intervention has the potential to have a beneficial effect on CAD
prognosis.
PMID- 27490430
TI - A second look: Efforts to repurpose old drugs against Zika cast a wide net.
PMID- 27490431
TI - Networking for resistance detection: FDA and CDC build repository of drug
resistant microbes.
PMID- 27490432
TI - Disease drivers: Global consortia aim to unpack genetics of diabetes and obesity.
PMID- 27490434
TI - CBLB ubiquitin ligase: a major regulator of antifungal immunity.
PMID- 27490433
TI - Understanding human immune function using the resources from the Human Functional
Genomics Project.
PMID- 27490435
TI - The brain's reward circuitry regulates immunity.
PMID- 27490436
TI - The role of muscle stem cell-niche interactions during aging.
PMID- 27490437
TI - Corrigendum: Nod2-mediated recognition of the microbiota is critical for mucosal
adjuvant activity of cholera toxin.
PMID- 27490438
TI - New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics:
Topological Metabolite Identification Carbon Efficiency (tMICE).
AB - A new, simple-to-implement and quantitative approach to assessing the confidence
in NMR-based identification of known metabolites is introduced. The approach is
based on a topological analysis of metabolite identification information
available from NMR spectroscopy studies and is a development of the metabolite
identification carbon efficiency (MICE) method. New topological metabolite
identification indices are introduced, analyzed, and proposed for general use,
including topological metabolite identification carbon efficiency (tMICE).
Because known metabolite identification is one of the key bottlenecks in either
NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies,
and given the fact that there is no current consensus on how to assess metabolite
identification confidence, it is hoped that these new approaches and the
topological indices will find utility.
PMID- 27490439
TI - Informing climate models with rapid chamber measurements of forest carbon uptake.
AB - Models predicting ecosystem carbon dioxide (CO2 ) exchange under future climate
change rely on relatively few real-world tests of their assumptions and outputs.
Here, we demonstrate a rapid and cost-effective method to estimate CO2 exchange
from intact vegetation patches under varying atmospheric CO2 concentrations. We
find that net ecosystem CO2 uptake (NEE) in a boreal forest rose linearly by 4.7
+/- 0.2% of the current ambient rate for every 10 ppm CO2 increase, with no
detectable influence of foliar biomass, season, or nitrogen (N) fertilization.
The lack of any clear short-term NEE response to fertilization in such an N
limited system is inconsistent with the instantaneous downregulation of
photosynthesis formalized in many global models. Incorporating an alternative
mechanism with considerable empirical support - diversion of excess carbon to
storage compounds - into an existing earth system model brings the model output
into closer agreement with our field measurements. A global simulation
incorporating this modified model reduces a long-standing mismatch between the
modeled and observed seasonal amplitude of atmospheric CO2 . Wider application of
this chamber approach would provide critical data needed to further improve
modeled projections of biosphere-atmosphere CO2 exchange in a changing climate.
PMID- 27490440
TI - Cerium(III) Complex Modified Gold Electrode: An Efficient Electrocatalyst for the
Oxygen Evolution Reaction.
AB - Exploring efficient and inexpensive electrocatalysts for the oxidation of water
is of great importance for various electrochemical energy storage and conversion
technologies. In the present study, a new water-soluble [Ce(III)(DMF) (HSO4)3]
complex was synthesized and characterized by UV-vis, photoluminescence, and high
resolution X-ray photoelectron spectroscopy techniques. Owing to classic 5d -> 4f
transitions, an intense photoluminescence in the UV region was observed from the
water-soluble [Ce(III)(DMF) (HSO4)3] complex. A stacking electrode was designed
where self-assembled l-cysteine monolayer modified gold was immobilized with the
synthesized cerium complex and was characterized by scanning electron microscopy,
electrochemical impedance spectroscopy, and cyclic voltammetry. The resulting
electrode, i.e., [Ce(III)(DMF) (HSO4)3]-l-cysteine-Au stacks shows high
electrocatalytic water oxidation behavior at an overpotential of eta ~ 0.34 V
under neutral pH conditions. We also demonstrated a way where the overpotential
is possible to decrease upon irradiation of UV light.
PMID- 27490441
TI - Genetic diversity and association analysis of leafminer (Liriomyza langei)
resistance in spinach (Spinacia oleracea).
AB - Leafminer (Liriomyza langei) is a major insect pest of many important
agricultural crops, including spinach (Spinacia oleracea). Use of genetic
resistance is an efficient, economic, and environment-friendly method to control
this pest. The objective of this research was to conduct association analysis and
identify single nucleotide polymorphism (SNP) markers associated with leafminer
resistance in spinach germplasm. A total of 300 USDA spinach germplasm accessions
were used for the association analysis of leafminer resistance. Genotyping by
sequencing (GBS) was used for genotyping and 783 SNPs from GBS were used for
association analysis. The leafminer resistance showed a near normal distribution
with a wide range from 1.1 to 11.7 stings per square centimeter leaf area,
suggesting that the leafminer resistance in spinach is a complex trait controlled
by multiple genes with minor effect in this spinach panel. Association analysis
indicated that five SNP markers, AYZV02040968_7171, AYZV02076752_412,
AYZV02098618_4615, AYZV02147304_383, and AYZV02271373_398, were associated with
the leafminer resistance with LOD 2.5 or higher. The SNP markers may be useful
for breeders to select plants and lines for leafminer resistance in spinach
breeding programs through marker-assisted selection.
PMID- 27490442
TI - The influence of flue gas desulphurization gypsum additive on characteristics and
evolution of humic substance during co-composting of dairy manure and sugarcane
pressmud.
AB - For the purpose of evaluating the effect of flue gas desulphurization gypsum
(FGDG) additive on characteristics and evolution of humic substance (HS) during
composting, HS from composts with FGDG (CPG) and without FGDG (CP) were extracted
and assessed with respect to their particle size, elemental analysis, FTIR and UV
vis spectroscopy, and the molecular composition of HS was characterized via
pyrolysis-GC/MS as well. The particle size of HS ranged between 300 and 600nm,
representing a bimodal distribution. As composting proceeded, the C/H of HS
increased, and C/N decreased. The FTIR and UV-vis spectroscopy indicated that the
aromatization of HS was promoted over the composting process. Adding FGDG
increased the unsaturated degree and aromatization of HS. Pyrolysis-GC/MS showed
the level of alkane decreased, and the level of benzene and nitrogen compounds
increased upon the addition of FGDG. The nitrogen compounds of HS in CPG was
significantly higher than that in CP.
PMID- 27490443
TI - A study on pyrolysis of Canada thistle (Cirsium arvense) with titania based
catalysts for bio-fuel production.
AB - The catalytic pyrolysis of Cirsium arvense was performed with titania supported
catalysts under the operating conditions of 500 degrees C, 40 degrees C/min
heating rate, 100mL/min N2 flow rate in a fixed bed reactor for biofuel
production. The effect of catalysts on product yields was investigated. The
amount of pyrolysis products (bio-char, bio-oil, gas) and the composition of the
produced bio-oils were determined by proton nuclear magnetic resonance ((1)H
NMR), Fourier transform infrared spectroscopy (FT-IR), gas chromatography/mass
spectrometry (GC-MS) and elemental analysis (EA) techniques. Thistle bio-oils had
lower O/C and H/C molar ratios compared to feedstock. The highest bio-char and
bio-oil yields of 29.32wt% and 36.71wt% were obtained in the presence of Ce/TiO2
and Ni/TiO2 catalysts respectively. GC-MS identified 97 different compounds in
the bio-oils obtained from thistle pyrolysis. (1)H NMR analysis showed that the
bio-oils contained ~55-77% aliphatic and ~6-19% aromatic structural units.
PMID- 27490444
TI - Current status of the influence of osteoporosis on periodontology and implant
dentistry.
AB - PURPOSE OF REVIEW: This review summarizes recent evidence on the impact of
osteoporosis on periodontonlogy and implant dentistry, prevalence of diseases,
pathophysiology and treatment outcomes. RECENT FINDINGS: Patients with
osteoporosis should be advised about the importance of returning for periodical
periodontal maintenance as inadequate oral care may lead to a faster development
of periodontitis. There is no definitive information on the development of
bisphosphonate-related osteonecrosis of the jaw associated with dental implant
therapy. Patients presenting severe periodontitis, undergoing intravenous
bisphosphonate therapy (for long-term periods) and submitted to more invasive
periodontal/peri-implant surgical procedures (that can promote superior
dentoalveolar surgical trauma) might be advised about the possibility of
developing bisphosphonate-related osteonecrosis of the jaw following dental
therapy. Thus, individualized risk evaluation must be undertaken by both the
medical and dental teams prior to any dental treatment. SUMMARY: The most recent
literature on the impact of osteoporosis on the periodontal and peri-implant
tissues was reviewed to emphasize the importance of oral hygiene measures, and
the combined medical/dental assessment of importance when osteoporotic patients
are in need of dentoalveolar surgical procedures (e.g. tooth extraction and
dental implant placement).
PMID- 27490445
TI - Similarities in the Retinal Appearance of Patients With Zika Virus Compared With
Cobalamin C Deficiency-Reply.
PMID- 27490448
TI - Assessment of Early Treatment Response With DWI After CT-Guided Radiofrequency
Ablation of Functioning Adrenal Adenomas.
AB - OBJECTIVE: The objective of this study was to establish the suitability of the
apparent diffusion coefficient (ADC) as a parameter for evaluating early
treatment response after percutaneous ablation of functional adrenal adenomas.
SUBJECTS AND METHODS: Seventeen adult patients with functioning adrenal adenomas
underwent radiofrequency ablation. Serum hormone levels were analyzed before and
up to 6 months after ablation. MRI findings (nodule size in cm, signal intensity
index, ADC maps, and nodule-to-muscle ADC ratio) were analyzed before and up to
30 days after ablation. A consensus review of all scans was performed by two
attending abdominal imaging radiologists. The procedure was considered successful
if serum hormone levels normalized and no contrast enhancement of the adrenal
lesion was seen on follow-up MRI. RESULTS: Of 17 patients who underwent
radiofrequency ablation, complete response was achieved in 16 patients with
partial response in one patient. Of the four parameters of interest, only ADC
maps and nodule-to-muscle ADC ratio showed statistically significant differences
(p < 0.05). CONCLUSION: This prospective study suggests that apparent diffusion
coefficient values may help radiologists monitor early treatment response after
CT-guided radiofrequency ablation of functioning adrenal adenomas.
PMID- 27490446
TI - Imaging lymphoid tissues in nonhuman primates to understand SIV pathogenesis and
persistence.
AB - CD4+ T cells are the primary HIV-1 target cell, with the vast majority of these
cells residing within lymphoid tissue compartments throughout the body.
Predictably, HIV-1 infection, replication, localization, reservoir establishment
and persistence, as well as associated host immune and inflammatory responses and
disease pathology principally take place within the tissues of the immune system.
By virture of the fact that the virus-host struggle is played out within lymphoid
and additional tissues compartments in HIV-1 infected individuals it is critical
to understand HIV-1 infection and disease within these relevant tissue sites;
however, there are obvious limitations to studying these dynamic processes in
humans. Nonhuman primate (NHP) research has provided a vital bridge between basic
and preclinical research and clinical studies, with experimental SIV infection of
NHP models offering unique opportunities to understand key processes of HIV-1
infection and disease that are either not practically feasible or ethical in HIV
1 infected humans. In this review we will discuss current approaches to studying
the tissue based immunopathogenesis of AIDS virus infection in NHPs, including
both analyses of tissues obtained at biopsy or necropsy and complementary non
invasive imaging approaches that may have practical utility in monitoring HIV-1
disease in the clinical setting.
PMID- 27490450
TI - Reducing Gender Discrepancies in Academic Radiology.
PMID- 27490449
TI - A statistical assessment of pesticide pollution in surface waters using
environmental monitoring data: Chlorpyrifos in Central Valley, California.
AB - Pesticides are routinely monitored in surface waters and resultant data are
analyzed to assess whether their uses will damage aquatic eco-systems. However,
the utility of the monitoring data is limited because of the insufficiency in the
temporal and spatial sampling coverage and the inability to detect and quantify
trace concentrations. This study developed a novel assessment procedure that
addresses those limitations by combining 1) statistical methods capable of
extracting information from concentrations below changing detection limits, 2)
statistical resampling techniques that account for uncertainties rooted in the
non-detects and insufficient/irregular sampling coverage, and 3) multiple lines
of evidence that improve confidence in the final conclusion. This procedure was
demonstrated by an assessment on chlorpyrifos monitoring data in surface waters
of California's Central Valley (2005-2013). We detected a significant downward
trend in the concentrations, which cannot be observed by commonly-used
statistical approaches. We assessed that the aquatic risk was low using a
probabilistic method that works with non-detects and has the ability to
differentiate indicator groups with varying sensitivity. In addition, we showed
that the frequency of exceedance over ambient aquatic life water quality criteria
was affected by pesticide use, precipitation and irrigation demand in certain
periods anteceding the water sampling events.
PMID- 27490451
TI - Synthesis of meta-Terphenyl-2,2''-diols by Anodic C-C Cross-Coupling Reactions.
AB - The anodic C-C cross-coupling reaction is a versatile synthetic approach to
symmetric and non-symmetric biphenols and arylated phenols. We herein present a
metal-free electrosynthetic method that provides access to symmetric and non
symmetric meta-terphenyl-2,2''-diols in good yields and high selectivity.
Symmetric derivatives can be obtained by direct electrolysis in an undivided
cell. The synthesis of non-symmetric meta-terphenyl-2,2''-diols required two
electrochemical steps. The reactions are easy to conduct and scalable. The method
also features a broad substrate scope, and a large variety of functional groups
are tolerated. The target molecules may serve as [OCO](3-) pincer ligands.
PMID- 27490452
TI - Recognition and Management of Perioperative Stroke in Hospitalized Patients.
AB - We sought to characterize stroke management and outcomes in a postoperative
population. By using the electronic medical records, we identified 39 patients
suffering perioperative stroke after noncardiac and nonneurosurgical procedures
for whom documentation of management and outcomes was available. Thirty-three
strokes occurred during admission, whereas 6 occurred after discharge and were
recognized upon return to the hospital. Perioperative stroke was associated with
delayed recognition, infrequent intervention, and significant rates of morbidity
and mortality, suggesting the need for improved screening and more rapid
treatment. There may be disparities in care and outcomes between in-hospital and
out-of hospital stroke patients, though further study is warranted.
PMID- 27490455
TI - Cellular uptake and anticancer activity of salvianolic acid B phospholipid
complex loaded nanoparticles in head and neck cancer and precancer cells.
AB - Salvianolic acid B (SalB) was demonstrated to be a promising chemopreventive
agent for head and neck squamous cell carcinoma (HNSCC) in the previous studies
by our and other research institution, but the properties like low efficacy, poor
systemic delivery, and low bioavailability has hampered its clinical
applications. To continue our research program focused on the use of natural
compounds on cancer chemoprevention, we propose a first example of phospholipid
complex loaded nanoparticles (PLC-NPs) encapsulating SalB as a potential carrier
for intervention of HNSCC (HN13, HN30) cells and precancer Leuk1 cells in this
study. Qualitative and quantitive studies of cellular uptake showed that
intracellular accumulation of SalB was significantly higher when HN13, HN30 and
Leuk1 cells were incubated with SalB-PLC-NPs complex (nano-SalB) as against free
SalB. Cell viability assay revealed that the cell growth of HN13 and HN30 cells
was significantly inhibited of 56.1% and 29.3%, respectively, for nano-SalB
compared to an equivalent amount of free-SalB (P<0.001). Moreover, cell cycle and
apoptosis assay showed that a clear trend of cell cycle arrest and induction of
apoptosis was also observed within the HNSCC cells treated with nano-SalB.
Collectively, this study demonstrated that nano-SalB was significantly more
potent had an anticancer effect against HNSCC cells, which serves as the first
step toward establishing SalB nano-formulations as promising cancer
chemopreventive agents. The current study could pave a new way for the
development of drugs that target HNSCC in the future.
PMID- 27490454
TI - A humanized osteopontin mouse model and its application in immunometabolic
obesity studies.
AB - Osteopontin (OPN) is a multifunctional protein involved in several inflammatory
processes and pathogeneses including obesity-related disorders and cancer. OPN
binds to a variety of integrin receptors and CD44 resulting in a proinflammatory
stimulus. Therefore, OPN constitutes a novel interesting target to develop new
therapeutic strategies, which counteract OPN's proinflammatory properties. We
established a humanized SPP1 (hSPP1) mouse model and evaluated its suitability as
a model for obesity and insulin resistance. Unchallenged hSPP1 animals did not
significantly differ in body weight and gross behavioral properties compared to
wild-type (WT) animals. High-fat diet-challenged hSPP1 similarly developed
obesity and inflammation, whereas insulin resistance was markedly changed.
However, OPN expression profile in tissues was significantly altered in hSPP1
compared to WT depending on the diet. In conclusion, we developed a versatile
humanized model to study the action of OPN in vivo and to develop strategies that
target human OPN in a variety of pathologies.
PMID- 27490453
TI - Microbiome, trimethylamine N-oxide, and cardiometabolic disease.
AB - There is increasing appreciation that changes in microbiome composition and
function can promote long-term susceptibility for cardiometabolic risk. Gut
microbe-derived metabolites that are biologically active, such as trimethylamine
N-oxide (TMAO), are now recognized as contributors to atherogenesis. This review
summarizes our current understanding of the role of TMAO in the pathogenesis of
cardiometabolic diseases and will discuss current findings, controversies, and
further perspectives in this new area of investigation. Better appreciation of
the interactions between dietary nutrient intake with gut microbiota-mediated
metabolism may provide clinical insights into defining individuals at risk for
disease progression in cardiometabolic diseases, as well as additional potential
therapeutic targets for reducing risks for cardiometabolic disease progression.
PMID- 27490456
TI - Spironolactone nanocrystals for oral administration: Different pharmacokinetic
performances induced by stabilizers.
AB - Nanocrystal (NC) technology is an effective strategy to enhance the oral
bioavailability for poorly water-soluble drugs. Stabilizers are essential and
important in NC formulations due to its ability to decrease the system energy.
Studies have revealed that stabilizers can affect the particle size and stability
of the system. However, whether stabilizers can affect the in vivo behaviors of
the NCs is unknown. To investigate the effects of stabilizers on the in vitro and
in vivo performances of NCs, four types of spironolactone (SPN) NCs with similar
diameters but different stabilizers were prepared. All the NCs were spherical in
shape with a size of about 370nm. In addition, the NCs were also characterized by
differential scanning calorimetry, X-ray diffraction, and Raman spectroscopy, the
results obtained showed that the SPN in all the formulations was partially
amorphous. In fasted state simulated intestinal fluid, all the SPN-NCs showed
similar dissolution profiles. However, the dissolution for SPN-NCs/NaDC was
suppressed in 0.1M HCl. Importantly, the AUC(0-48h)total for SPN-NCs/F127, SPN
NCs/F68, SPN-NCs/HPMC-E5, and SPN-NCs/NaDC was 4.96-, 3.91-, 2.88- and 1.72-fold
higher than that of the SPN suspension, respectively. These results demonstrated
that stabilizers in NCs played an important role for the in vivo pharmacokinetic
behaviors. It is highly suggested that the ionic stabilizers are not suitable to
stabilize drug nanocrystals alone because it may induce aggregation and
agglomeration of drug crystals when transferring through the whole
gastrointestinal tract and experiencing the different pH levels.
PMID- 27490457
TI - A Structural Magnetic Resonance Imaging Study in Transgender Persons on Cross-Sex
Hormone Therapy.
AB - BACKGROUND: To date, research findings are inconsistent about whether the
neuroanatomy in transgender persons resembles that of their natal sex or their
gender identity. Moreover, few studies have examined the effects of long-term
cross-sex hormonal treatment on neuroanatomy in this cohort. The purpose of the
present study was to examine neuroanatomical differences in transgender persons
after prolonged cross-sex hormone therapy. METHODS: Eighteen transgender men
(female-to-male), 17 transgender women (male-to-female), 30 nontransgender men
(natal men), and 27 nontransgender women (natal women) completed a high
resolution structural magnetic resonance imaging scan at 3 T. Eligibility
criteria for transgender persons were gender-affirming surgery and at least 2
years of cross-sex hormone therapy. Exclusion criteria for nontransgender persons
were presence of psychiatric or neurological disorders. RESULTS: The mean
neuroanatomical volume for the amygdala, putamen, and corpus callosum differed
between transgender women and natal women but not between transgender women and
natal men. Differences between transgender men and natal men were found in
several brain structures, including the medial temporal lobe structures and
cerebellum. Differences between transgender men and natal women were found in the
medial temporal lobe, nucleus accumbens, and 3rd ventricle. Sexual dimorphism
between nontransgender men and women included larger cerebellar volumes and a
smaller anterior corpus callosum in natal men than in natal women. The results
remained stable after correcting for additional factors including age, total
intracranial volume, anxiety, and depressive symptoms. CONCLUSIONS:
Neuroanatomical differences were region specific between transgender persons and
their natal sex as well as their gender identity, raising the possibility of a
localized influence of sex hormones on neuroanatomy.
PMID- 27490459
TI - Noncovalent Dimerization after Enediyne Cyclization on Au(111).
AB - We investigate the thermally induced cyclization of 1,2-bis(2
phenylethynyl)benzene on Au(111) using scanning tunneling microscopy and computer
simulations. Cyclization of sterically hindered enediynes is known to proceed via
two competing mechanisms in solution: a classic C(1)-C(6) (Bergman) or a C(1)
C(5) cyclization pathway. On Au(111), we find that the C(1)-C(5) cyclization is
suppressed and that the C(1)-C(6) cyclization yields a highly strained bicyclic
olefin whose surface chemistry was hitherto unknown. The C(1)-C(6) product self
assembles into discrete noncovalently bound dimers on the surface. The reaction
mechanism and driving forces behind noncovalent association are discussed in
light of density functional theory calculations.
PMID- 27490458
TI - The roles of AtxA orthologs in virulence of anthrax-like Bacillus cereus G9241.
AB - AtxA is a critical transcriptional regulator of plasmid-encoded virulence genes
in Bacillus anthracis. Bacillus cereus G9241, which caused an anthrax-like
infection, has two virulence plasmids, pBCXO1 and pBC210, that each harbor toxin
genes and a capsule locus. G9241 also produces two orthologs of AtxA: AtxA1,
encoded on pBCXO1, and AtxA2, encoded on pBC210. The amino acid sequence of AtxA1
is identical to that of AtxA from B. anthracis, while the sequences of AtxA1 and
AtxA2 are 79% identical and 91% similar to one another. We found by qRT-PCR that
AtxA1 and AtxA2 function as positive regulators of toxin (AtxA1) and capsule
operon (both) transcription in G9241 and that a DeltaatxA1 mutant produced lower
levels of the anthrax toxins and no hyaluronic acid capsule. Deletion of atxA1 or
atxA2 decreased the virulence of spores administered intranasally or
subcutaneously to C57BL/6 mice but not to A/J mice, and deletion of both genes
rendered spores avirulent in A/J mice. In addition, unlike AtxA1, AtxA2 did not
form stable homomultimers in vitro, although AtxA1 and AtxA2 formed heterodimers.
Our data show that AtxA1 is the primary regulator of G9241 virulence factor
expression and that AtxA1 and AtxA2 are both required for full virulence.
PMID- 27490460
TI - Young Women's Contraceptive Decision Making: Do Preferences for Contraceptive
Attributes Align with Method Choice?
AB - CONTEXT: Understanding how women's preferences for certain attributes of
contraceptive methods relate to their method choice can inform the content of
contraceptive counseling. METHODS: Data from 715 women aged 18-29 who had ever
used contraceptives were drawn from the 2009 National Survey of Reproductive and
Contraceptive Knowledge. Chi-square tests and multivariable logistic regression
analyses were used to examine how women's preferences for specific contraceptive
attributes were related to their social and demographic characteristics and their
current contraceptive choice. RESULTS: The majority of women considered it
extremely important for a method to be very effective at preventing pregnancy
(79%) and to be effective at preventing HIV and STDs (67%); fewer than one
quarter felt similarly about a method's being hormone-free (22%). Women who felt
it was quite or extremely important for a method to be very effective at
preventing pregnancy were not more likely to use the most effective methods than
were women who considered this attribute not at all or only slightly important.
Women who considered it quite or extremely important for a method to be hormone
free were less likely than others to use hormonal methods (odds ratio, 0.4), and
women who considered STD protection quite or extremely important had elevated
odds of relying on condoms alone, rather than on an effective contraceptive
method alone (3.6). CONCLUSIONS: Most women desire a very effective method for
pregnancy prevention, but it is unclear how this translates to their
contraceptive use. The associations between women's preferred contraceptive
attributes and method choice warrant further attention.
PMID- 27490462
TI - Impact Factors and Prediction of Popular Topics in a Journal.
AB - The impact factor (IF) for 2015 was recently released and this could be the time
to once again reflect on its use as a metric of a journal. Problems and concerns
regarding the IF have been addressed extensively elsewhere 1 2. The principle of
the IF for a given year is that it represents the average number of citations of
articles published in the journal in the two previous years.While authors
frequently cite the IF as a determining factor for submission, the IF does not
predict how many times individual articles will be cited. In a study from a peer
reviewed cardiovascular journal, nearly half of all published articles were
poorly cited, i. e., less than five citations in five years 3. A similar
percentage seems to apply to our journal. In nearly all journals we estimate that
the majority of citations relate to a minority of the articles. Some articles are
never cited. 13 % of the articles published in our journal from 2010 to 2013 have
never been cited. Even authors of poorly cited articles benefit from the IF since
many institutions use the combined impact factors of their published papers to
measure research activity and this may be reflected in their research budgets.The
competition for the printed pages in the six annual issues of Ultraschall in der
Medizin/European Journal of Ultrasound (UiM/EJU) has resulted in high rejection
rates (between 80 % and 90 %). One negative review with recommendation of major
revision may therefore result in rejection. Peer-review fraud where the
submitting author listed recommended reviewers with fake email addresses
supplying fabricated peer reviews has recently been described in the New England
Journal of Medicine 4. Some of the editors of our journal believe they have
experienced this as well. Fabricating reviews in order to get a high IF for an
article is to be considered fraud and is inexcusable.One aspect of using impact
factors as a measure of the quality of a journal is that the IF only goes back
two years. There may be differences between journals for different medical
specialties since the citations in some areas seem to "burn out" within a few
years while some articles continue to be cited even after several years.
Therefore, a citation window that is longer than 2 years has been proposed 5.For
this editorial we took a look at the 60 articles published in UiM/EJU in 2010.
Half of them were no longer being cited in 2015. However, 10 articles were cited
more than 5 times in 2015, and 5 of these were cited more than 10 times 6 7 8 9
10. It therefore seems that many of our articles have a long scientific life and
generate more citations than indicated by the IF. Moreover, some articles have
the highest number of citations after three years when they are no longer
contributing to the impact factor. The most frequently cited articles from 2010
were multicenter studies, recommendations, and papers on hot topics like contrast
enhanced ultrasound (CEUS) and elastography, but it should be noted that there
were also articles on the same topics that were poorly cited.The same trending
topics continued into 2013 now topped by European guidelines and recommendations
11 12 13. 9 of the 10 most cited articles we published in 2014 were on CEUS or
elastography 14 15 16 17 18 19 20 21 22, but the most cited article from that
year so far has been on peripheral nerves 23. Surprisingly many good scientific
papers on obstetrics/fetal US and musculoskeletal US have low citation rates 24
25 26. Our predictions for 2016 based on the topics of submitted articles in the
last 12 months are that CEUS and elastography will continue to be popular
topics.It is also worth mentioning that there can be a discrepancy between which
titles are cited and which are accessed online. In addition to international
guidelines, our CME articles are usually popular according to online access. CME
articles are well established educational papers but they are rarely cited for
the IF. Looking at the most read full-text recent articles on our journal's
website shows that multicenter studies as well as recommendations backed by a
national society or by the EFSUMB (European Federation of Societies for
Ultrasound in Medicine and Biology) are still important 27 28 29 30 31 32 33.
Upcoming important topics appear to be pediatric use of CEUS, simulation training
and the introduction of ultrasound to medical students 34 35 36 37. Some of these
are also backed by EFSUMB.A recent paper on the IF of radiology journals found
that subspecialty radiology journals had a higher IF than general radiology
journals 38. This could prove a challenge to interdisciplinary journals like ours
but we take pride in continuing to cover all aspects of ultrasound in more than
15 fields.The distribution between reviews, original articles and case reports in
a journal is worth addressing. An important aspect of a journal is the
publication of original scientific research articles. CME articles, pictorials
and letters are important for other reasons but are cited at a lower rate. The
value of case reports with regard to the IF is low since they are rarely cited 39
and we have observed that some journals have abandoned the publication of case
reports, thus leaving them to spin-off journals. The rationale is that keeping
case reports in a journal will only increase the denominator, thereby decreasing
the IF 39. At our journal we have seen a decline in case report submissions but
still want to publish them and even put one case on the front cover of every
issue. Case reports still hold an educational value 40 and are important to our
readers.In conclusion, a healthy mix of original articles, CME articles, reviews
and case reports combined with a few international guidelines and recommendations
is important to UIM/EJU. Although we see popular topics like CEUS and
elastography, it is not possible to predict which articles will be read or even
cited based on the topic, with multicenter studies being the exception.
PMID- 27490461
TI - Dyschloremia Is a Risk Factor for the Development of Acute Kidney Injury in
Critically Ill Patients.
AB - INTRODUCTION: Dyschloremia is common in critically ill patients, although its
impact has not been well studied. We investigated the epidemiology of
dyschloremia and its associations with the incidence of acute kidney injury and
other intensive care unit outcomes. MATERIAL AND METHODS: This is a single
center, retrospective cohort study at Mayo Clinic Hospital-Rochester. All adult
patients admitted to intensive care units from January 1st, 2006, through
December 30th, 2012 were included. Patients with known acute kidney injury and
chronic kidney disease stage 5 before intensive care unit admission were
excluded. We evaluated the association of dyschloremia with ICU outcomes, after
adjustments for the effect of age, gender, Charlson comorbidity index and
severity of illness score. RESULTS: A total of 6,025 patients were enrolled in
the final analysis following the implementation of eligibility criteria. From the
cohort, 1,970 patients (33%) developed acute kidney injury. Of the total patients
enrolled, 4,174 had a baseline serum chloride. In this group, 1,530 (37%) had
hypochloremia, and 257 (6%) were hyperchloremic. The incidence of acute kidney
injury was higher in hypochloremic and hyperchloremic patients compared to those
with a normal serum chloride level (43% vs.30% and 34% vs. 30%, respectively; P <
.001). Baseline serum chloride was lower in the acute kidney injury group vs. the
non-acute kidney injury group [100 mmol/L (96-104) vs. 102 mmol/L (98-105), P <
.0001]. In a multivariable logistic regression model, baseline serum chloride of
<=94 mmol/L found to be independently associated with the risk of acute kidney
injury (OR 1.7, 95% CI 1.1-2.6; P = .01). DISCUSSION: Dyschloremia is common in
critically ill patients, and severe hypochloremia is independently associated
with an increased risk of development of acute kidney injury.
PMID- 27490463
TI - EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V - EUS-Guided
Therapeutic Interventions (short version).
AB - The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the
European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB)
assesses the evidence for all the categories of endoscopic ultrasound-guided
treatment reported to date. Celiac plexus neurolysis and block, vascular
intervention, drainage of fluid collections, drainage of biliary and pancreatic
ducts, and experimental tumor ablation techniques are discussed. For each topic,
all current evidence has been extensively analyzed and summarized into major
recommendations for reader consultation (short version; the long version is
published online).
PMID- 27490464
TI - Nachlese Dreilandertreffen 2015.
PMID- 27490465
TI - Mini-breast reconstruction with an omental flap: a retrospective clinical study.
AB - INTRODUCTION: Potential challenges associated with immediate small breast
reconstruction include an inadequate size of the donor site, a thinner skin
envelope and limited selection of implants. We present immediate postmastectomy
reconstruction of small breasts with a laparoscopically harvested pedicled
omental flap (LHPOF) in five Korean women. METHODS: From December 2014 to July
2015, we performed immediate postmastectomy reconstruction with an LHPOF in five
breast cancer patients. Data on the patients' age; body mass index; tumour size;
site, type and weight of the mastectomy specimen; operative time; hospital stay;
complications; postoperative chemotherapy or radiation therapy; and follow-up
duration were reviewed in this retrospective clinical study. RESULTS: The mean
mastectomy specimen weight was 212 g (range: 104-272 g). The mean operative time
was 298 min (range: 240-380 min), and the mean harvesting time was 75 min (range:
65-90 min). There were no flap-related complications such as fat necrosis or flap
loss and no donor site-related complications such as bowel dysfunction, an
epigastric bulge or hernia during the follow-up period (average: 8.2 months,
range: 5-11 months). The cosmetic results were satisfactory. DISCUSSION: The
LHPOF can be useful for immediate postmastectomy reconstruction of small breasts,
because it provides a soft and naturally ptotic appearance of the reconstructed
breast (versus implant-based reconstruction) with low donor-site morbidity
(versus other autologous tissue reconstruction approaches).
PMID- 27490466
TI - Bis-Boron Compounds in Catalysis: Bidentate and Bifunctional Activation.
AB - The development of metal-free catalysts as an alternative to the use of
transition metals has gained tremendous interest in the past. In catalysis, Lewis
acidity is one of the major principles used for the activation of organic
compounds. Improving the reactivity and selectivity of Lewis acids by utilizing
bidentate interactions was already proposed 50 years ago. Nevertheless, product
inhibition due to strong binding has made applications of bidentate Lewis acids
challenging for many years. Recently, bis-boron compounds have been found to be
very effective and several applications in Diels-Alder reactions, carbon dioxide
reduction, and ammonia-borane dehydrogenation were reported. All three
transformations are enabled by the catalyst at different stages during the course
of the reaction. These new and useful examples illustrate the great potential of
the concept.
PMID- 27490467
TI - HER-2 and EGFR mRNA Expression and Its Relationship with Versican in Malignant
Matrix-Producing Tumors of the Canine Mammary Gland.
AB - Versican expression promotes tumor growth by destabilizing focal cell contacts,
thus impeding cell adhesion and facilitating cell migration. It not only presents
or recruits molecules to the cell surface, but also modulates gene expression
levels and coordinates complex signal pathways. Previously, we suggested that the
interaction between versican and human epidermal growth factor receptors may be
directly associated with tumor aggressiveness. Thus, the expression of EGFR and
HER-2 in these neoplasms may contribute to a better understanding of the
progression mechanisms in malignant mammary tumors. The purpose of this study was
to correlate the gene and protein expressions of EGFR and HER2 by RNA In Situ
Hybridization (ISH) and immunohistochemistry (IHC), respectively, and their
relationship with the versican expression in carcinomas in mixed tumors and
carcinosarcomas of the canine mammary gland. The results revealed that EGFR mRNA
expression showed a significant difference between in situ and invasive
carcinomatous areas in low and high versican expression groups. Identical results
were observed in HER-2 mRNA expression. In immunohistochemistry analysis,
neoplasms with low versican expression showed greater EGFR immunostaining in the
in situ areas than in invasive areas, even as the group presenting high versican
expression displayed greater EGFR and HER-2 staining in in situ areas.
Significant EGFR and HER-2 mRNA and protein expressions in in situ carcinomatous
sites relative to invasive areas suggest that these molecules play a role during
the early stages of tumor progression.
PMID- 27490469
TI - Disability Divides in India: Evidence from the 2011 Census.
AB - BACKGROUND: Understanding the socioeconomic and regional divides in disability
prevalence in India has considerable relevance for designing public health
policies and programs. OBJECTIVES: The aim of the present study is to quantify
the prevalence of disability by gender, region (rural and urban; states and
districts), and caste. We also examine the association between disability
prevalence and the major socio-demographic and socioeconomic characteristics of
the districts in India. METHODS: Age-standardized disability prevalence (ASDP)
was calculated using 2011 census data and applying the WHO World Standard
Population. A regression analysis was carried out to examine the association
between disability prevalence and demographic and socioeconomic characteristics
across districts of India. RESULTS: The study found that ASDP varies
substantially across districts and is higher among women, rural dwellers, and
members of scheduled tribes (STs) and scheduled castes (SCs). The regression
model showed that the disability rate in districts rises with increasing
proportions of the population who are urban dwellers, aged 65 or older, members
of STs, and living in dilapidated housing; and that the disability prevalence
decreases with increasing proportions of the female population who are literate,
and of the general population who are working and have access to safe drinking
water. CONCLUSION: As the burden of disability falls disproportionately across
geographic regions and socioeconomic groups, public health policies in India
should take this variation into account. The definition of disability used in the
census should be modified to generate internationally comparable estimates of
disability prevalence.
PMID- 27490468
TI - Bleeding Risk with Long-Term Low-Dose Aspirin: A Systematic Review of
Observational Studies.
AB - BACKGROUND: Low-dose aspirin has proven effectiveness in secondary and primary
prevention of cardiovascular events, but is also associated with an increased
risk of major bleeding events. For primary prevention, this absolute risk must be
carefully weighed against the benefits of aspirin; such assessments are currently
limited by a lack of data from general populations. METHODS: Systematic searches
of Medline and Embase were conducted to identify observational studies published
between 1946 and 4 March 2015 that reported the risks of gastrointestinal (GI)
bleeding or intracranial hemorrhage (ICH) with long-term, low-dose aspirin (75
325 mg/day). Pooled estimates of the relative risk (RR) for bleeding events with
aspirin versus non-use were calculated using random-effects models, based on
reported estimates of RR (including odds ratios, hazard ratios, incidence rate
ratios and standardized incidence ratios) in 39 articles. FINDINGS: The incidence
of GI bleeding with low-dose aspirin was 0.48-3.64 cases per 1000 person-years,
and the overall pooled estimate of the RR with low-dose aspirin was 1.4 (95%
confidence interval [CI]: 1.2-1.7). For upper and lower GI bleeding, the RRs with
low-dose aspirin were 2.3 (2.0-2.6) and 1.8 (1.1-3.0), respectively. Neither
aspirin dose nor duration of use had consistent effects on RRs for upper GI
bleeding. The estimated RR for ICH with low-dose aspirin was 1.4 (1.2-1.7)
overall. Aspirin was associated with increased bleeding risks when combined with
non-steroidal anti-inflammatory drugs, clopidogrel and selective serotonin
reuptake inhibitors compared with monotherapy. By contrast, concomitant use of
proton pump inhibitors decreased upper GI bleeding risks relative to aspirin
monotherapy. CONCLUSIONS: The risks of major bleeding with low-dose aspirin in
real-world settings are of a similar magnitude to those reported in randomized
trials. These data will help inform clinical judgements regarding the use of low
dose aspirin in prevention of cardiovascular events.
PMID- 27490471
TI - Erratum.
PMID- 27490472
TI - Posterior Shoulder Instability in Athletes.
PMID- 27490470
TI - Effective Cellular Morphology Analysis for Differentiation Processes by a
Fluorescent 1,3a,6a-Triazapentalene Derivative Probe in Live Cells.
AB - Nuclear and cytoplasmic morphological changes provide important information about
cell differentiation processes, cell functions, and signal responses. There is a
strong desire to develop a rapid and simple method for visualizing cytoplasmic
and nuclear morphology. Here, we developed a novel and rapid method for probing
cellular morphological changes of live cell differentiation process by a
fluorescent probe, TAP-4PH, a 1,3a,6a-triazapentalene derivative. TAP-4PH showed
high fluorescence in cytoplasmic area, and visualized cytoplasmic and nuclear
morphological changes of live cells during differentiation. We demonstrated that
TAP-4PH visualized dendritic axon and spine formation in neuronal
differentiation, and nuclear structural changes during neutrophilic
differentiation. We also showed that the utility of TAP-4PH for visualization of
cytoplasmic and nuclear morphologies of various type of live cells. Our
visualizing method has no toxicity and no influence on the cellular
differentiation and function. The cell morphology can be rapidly observed after
addition of TAP-4PH and can continue to be observed in the presence of TAP-4PH in
cell culture medium. Moreover, TAP-4PH can be easily removed after observation by
washing for subsequent biological assay. Taken together, these results
demonstrate that our visualization method is a powerful tool to probe
differentiation processes before subsequent biological assay in live cells.
PMID- 27490473
TI - Skeletal Repair in Distraction Osteogenesis: Mechanisms and Enhancements.
PMID- 27490474
TI - Arthroscopic Treatment of Pincer-Type Impingement of the Hip.
PMID- 27490475
TI - Advances in Pediatric Limb Lengthening: Part 1.
PMID- 27490476
TI - Editorial for the Special Issue on Photocatalysis.
PMID- 27490477
TI - Impact of Health System Inputs on Health Outcome: A Multilevel Longitudinal
Analysis of Botswana National Antiretroviral Program (2002-2013).
AB - OBJECTIVE: To measure the association between the number of doctors, nurses and
hospital beds per 10,000 people and individual HIV-infected patient outcomes in
Botswana. DESIGN: Analysis of routinely collected longitudinal data from 97,627
patients who received ART through the Botswana National HIV/AIDS Treatment
Program across all 24 health districts from 2002 to 2013. Doctors, nurses, and
hospital bed density data at district-level were collected from various sources.
METHODS: A multilevel, longitudinal analysis method was used to analyze the data
at both patient- and district-level simultaneously to measure the impact of the
health system input at district-level on probability of death or loss-to-follow
up (LTFU) at the individual level. A marginal structural model was used to
account for LTFU over time. RESULTS: Increasing doctor density from one doctor to
two doctors per 10,000 population decreased the predicted probability of death
for each patient by 27%. Nurse density changes from 20 nurses to 25 nurses
decreased the predicted probability of death by 28%. Nine percent decrease was
noted in predicted mortality of an individual in the Masa program for every five
hospital bed density increase. CONCLUSION: Considerable variation was observed in
doctors, nurses, and hospital bed density across health districts. Predictive
margins of mortality and LTFU were inversely correlated with doctor, nurse and
hospital bed density. The doctor density had much greater impact than nurse or
bed density on mortality or LTFU of individual patients. While long-term
investment in training more healthcare professionals should be made,
redistribution of available doctors and nurses can be a feasible solution in the
short term.
PMID- 27490478
TI - Inhibition of Pancreatic Cancer Cell-Induced Paracrine Hedgehog Signaling by
Liver X Receptor Agonists and Oxy16, a Naturally Occurring Oxysterol.
AB - The widespread involvement of the Hedgehog (Hh) signaling pathway in human
malignancies has driven efforts to develop Hh pathway inhibitors as anti-cancer
agents. The majority of these agents antagonize Smoothened (Smo), a plasma
membrane-associated signal transducer molecule. However, several such Smo
antagonists have failed in clinical trials to benefit patients with cancers that
arise from aberrant Hh signaling (which often bypasses Smo). In this study, we
report that a naturally occurring oxysterol, 20alpha, 22(R)-dihydroxycholesterol
(Oxy16), a known metabolite in the biosynthesis of steroid hormones, strongly
inhibits Hh signaling induced in C3H10T1/2 embryonic fibroblasts and NIH3T3-E1
fibroblasts through a mechanism that is independent of liver X receptor (LXR)
activation. We demonstrate that Oxy16 inhibits Hh signaling in Suppressor of
Fused (Sufu) null mouse embryonic fibroblast (MEF) cells, indicating that its
inhibitory effect on Hh signaling is epistatic to Sufu. We further demonstrate
that Oxy16 inhibits Gli1 transcriptional activity in NIH3T3-E1 cells
overexpressing Gli1 and a Gli-dependent reporter construct. Altogether, data
presented here suggest that Oxy16 may be a suitable starting point for the
development of new drugs that inhibit Hh signaling downstream of Smo. By
targeting aberrant Hh signaling, such novel Hh pathway inhibitors could
significantly broaden the range of clinical applications compared to existing Smo
antagonists. Furthermore, the present study adds a new facet to the spectrum of
Hh pathway modulation that naturally occurring oxysterol derivatives are capable
of, ranging from allosteric activation of the pathway via Smo binding to
inhibition of the pathway downstream of Smo. J. Cell. Biochem. 118: 499-509,
2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490479
TI - Structure of the ent-Copalyl Diphosphate Synthase PtmT2 from Streptomyces
platensis CB00739, a Bacterial Type II Diterpene Synthase.
AB - Terpenoids are the largest and most structurally diverse family of natural
products found in nature, yet their presence in bacteria is underappreciated. The
carbon skeletons of terpenoids are generated through carbocation-dependent
cyclization cascades catalyzed by terpene synthases (TSs). Type I and type II TSs
initiate cyclization via diphosphate ionization and protonation, respectively,
and protein structures of both types are known. Most plant diterpene synthases
(DTSs) possess three alpha-helical domains (alphabetagamma), which are thought to
have arisen from the fusion of discrete, ancestral bacterial type I TSs (alpha)
and type II TSs (betagamma). Type II DTSs of bacterial origin, of which there are
no structurally characterized members, are a missing piece in the structural
evolution of TSs. Here, we report the first crystal structure of a type II DTS
from bacteria. PtmT2 from Streptomyces platensis CB00739 was verified as an ent
copalyl diphosphate synthase involved in the biosynthesis of platensimycin and
platencin. The crystal structure of PtmT2 was solved at a resolution of 1.80 A,
and docking studies suggest the catalytically active conformation of
geranylgeranyl diphosphate (GGPP). Site-directed mutagenesis confirmed residues
involved in binding the diphosphate moiety of GGPP and identified DxxxxE as a
potential Mg(2+)-binding motif for type II DTSs of bacterial origin. Finally,
both the shape and physicochemical properties of the active sites are responsible
for determining specific catalytic outcomes of TSs. The structure of PtmT2
fundamentally advances the knowledge of bacterial TSs, their mechanisms, and
their role in the evolution of TSs.
PMID- 27490480
TI - Nutrition Screening Tools and the Prediction of Clinical Outcomes among Chinese
Hospitalized Gastrointestinal Disease Patients.
AB - Nutrition risk Screening 2002 (NRS-2002) and Subjective Global Assessment (SGA)
are widely used screening tools but have not been compared in a Chinese
population. We conducted secondary data analysis of a cross-sectional study which
included 332 hospitalized gastrointestinal disease patients, collected by the
Gastrointestinal department of Peking Union Medical College Hospital (PUMCH) in
2008. Results of NRS-2002 and SGA screening tools, complications, length of stay
(LOS), cost, and death were measured. The agreement between the tools was
assessed via Kappa (kappa) statistics. The performance of NRS-2002 and SGA in
predicting LOS and cost was assessed via linear regression. The complications and
death prediction of tools was assessed using receiver operating characteristic
(ROC) curves. NRS-2002 and SGA identified nutrition risk at 59.0% and 45.2%
respectively. Moderate agreement (kappa >0.50) between the two tools was found
among all age groups except individuals aged <= 20, which only slight agreement
was found (kappa = 0.087). NRS-2002 (R square 0.130) and SGA (R square 0.140) did
not perform differently in LOS prediction. The cost prediction of NRS-2002 (R
square 0.198) and SGA (R square 0.190) were not significantly different. There
was no difference between NRS-2002 (infectious complications: area under ROC
(AUROC) = 0.615, death: AUROC = 0.810) and SGA (infectious complications: AUROC =
0.600, death: AUROC = 0.846) in predicting infectious complication and death, but
NRS-2002 (0.738) seemed to perform better than SGA (0.552) in predicting non
infectious complications. The risk of malnutrition among patients was high. NRS
2002 and SGA have similar capacity to predict LOS, cost, infectious complications
and death, but NRS-2002 performed better in predicting non-infectious
complications.
PMID- 27490481
TI - Distinct roles of visual, parietal, and frontal motor cortices in memory-guided
sensorimotor decisions.
AB - Mapping specific sensory features to future motor actions is a crucial capability
of mammalian nervous systems. We investigated the role of visual (V1), posterior
parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice
during performance of a memory-guided visual discrimination task. Large-scale
calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous
responses spanning all task epochs (stimulus, delay, response). Population
analyses demonstrated unique encoding of stimulus identity and behavioral choice
information across regions, with V1 encoding stimulus, fMC encoding choice even
early in the trial, and PPC multiplexing the two variables. Optogenetic
inhibition during behavior revealed that all regions were necessary during the
stimulus epoch, but only fMC was required during the delay and response epochs.
Stimulus identity can thus be rapidly transformed into behavioral choice,
requiring V1, PPC, and fMC during the transformation period, but only fMC for
maintaining the choice in memory prior to execution.
PMID- 27490483
TI - Structures of TorsinA and its disease-mutant complexed with an activator reveal
the molecular basis for primary dystonia.
AB - The most common cause of early onset primary dystonia, a neuromuscular disease,
is a glutamate deletion (DeltaE) at position 302/303 of TorsinA, a AAA+ ATPase
that resides in the endoplasmic reticulum. While the function of TorsinA remains
elusive, the DeltaE mutation is known to diminish binding of two TorsinA ATPase
activators: lamina-associated protein 1 (LAP1) and its paralog, luminal domain
like LAP1 (LULL1). Using a nanobody as a crystallization chaperone, we obtained a
1.4 A crystal structure of human TorsinA in complex with LULL1. This nanobody
likewise stabilized the weakened TorsinADeltaE-LULL1 interaction, which enabled
us to solve its structure at 1.4 A also. A comparison of these structures shows,
in atomic detail, the subtle differences in activator interactions that separate
the healthy from the diseased state. This information may provide a structural
platform for drug development, as a small molecule that rescues TorsinADeltaE
could serve as a cure for primary dystonia.
PMID- 27490482
TI - MYC activation and BCL2L11 silencing by a tumour virus through the large-scale
reconfiguration of enhancer-promoter hubs.
AB - Lymphomagenesis in the presence of deregulated MYC requires suppression of MYC
driven apoptosis, often through downregulation of the pro-apoptotic BCL2L11 gene
(Bim). Transcription factors (EBNAs) encoded by the lymphoma-associated Epstein
Barr virus (EBV) activate MYC and silence BCL2L11. We show that the EBNA2
transactivator activates multiple MYC enhancers and reconfigures the MYC locus to
increase upstream and decrease downstream enhancer-promoter interactions. EBNA2
recruits the BRG1 ATPase of the SWI/SNF remodeller to MYC enhancers and BRG1 is
required for enhancer-promoter interactions in EBV-infected cells. At BCL2L11, we
identify a haematopoietic enhancer hub that is inactivated by the EBV repressors
EBNA3A and EBNA3C through recruitment of the H3K27 methyltransferase EZH2.
Reversal of enhancer inactivation using an EZH2 inhibitor upregulates BCL2L11 and
induces apoptosis. EBV therefore drives lymphomagenesis by hijacking long-range
enhancer hubs and specific cellular co-factors. EBV-driven MYC enhancer
activation may contribute to the genesis and localisation of MYC-Immunoglobulin
translocation breakpoints in Burkitt's lymphoma.
PMID- 27490484
TI - The selectivity of the Na(+)/K(+)-pump is controlled by binding site protonation
and self-correcting occlusion.
AB - The Na(+)/K(+)-pump maintains the physiological K(+) and Na(+) electrochemical
gradients across the cell membrane. It operates via an 'alternating-access'
mechanism, making iterative transitions between inward-facing (E1) and outward
facing (E2) conformations. Although the general features of the transport cycle
are known, the detailed physicochemical factors governing the binding site
selectivity remain mysterious. Free energy molecular dynamics simulations show
that the ion binding sites switch their binding specificity in E1 and E2. This is
accompanied by small structural arrangements and changes in protonation states of
the coordinating residues. Additional computations on structural models of the
intermediate states along the conformational transition pathway reveal that the
free energy barrier toward the occlusion step is considerably increased when the
wrong type of ion is loaded into the binding pocket, prohibiting the pump cycle
from proceeding forward. This self-correcting mechanism strengthens the overall
transport selectivity and protects the stoichiometry of the pump cycle.
PMID- 27490485
TI - Functional Translational Readthrough: A Systems Biology Perspective.
AB - Translational readthrough (TR) has come into renewed focus because systems
biology approaches have identified the first human genes undergoing functional
translational readthrough (FTR). FTR creates functional extensions to proteins by
continuing translation of the mRNA downstream of the stop codon. Here we review
recent developments in TR research with a focus on the identification of FTR in
humans and the systems biology methods that have spurred these discoveries.
PMID- 27490486
TI - In vivo targeting of metastatic breast cancer via tumor vasculature-specific nano
graphene oxide.
AB - Angiogenesis, i.e. the formation of neovasculatures, is a critical process during
cancer initiation, progression, and metastasis. Targeting of angiogenic markers
on the tumor vasculature can result in more efficient delivery of nanomaterials
into tumor since no extravasation is required. Herein we demonstrated efficient
targeting of breast cancer metastasis in an experimental murine model with nano
graphene oxide (GO), which was conjugated to a monoclonal antibody (mAb) against
follicle-stimulating hormone receptor (FSHR). FSHR has been confirmed to be a
highly selective tumor vasculature marker, which is abundant in both primary and
metastatic tumors. These functionalized GO nano-conjugates had diameters of ~120
nm based on atomic force microscopy (AFM), TEM, and dynamic laser scattering
(DLS) measurement. (64)Cu was incorporated as a radiolabel which enabled the
visualization of these GO conjugates by positron emission tomography (PET)
imaging. Breast cancer lung metastasis model was established by intravenous
injection of click beetle green luciferase-transfected MDA-MB-231 (denoted as
cbgLuc-MDA-MB-231) breast cancer cells into female nude mice and the tumor growth
was monitored by bioluminescence imaging (BLI). Systematic in vitro and in vivo
studies have been performed to investigate the stability, targeting efficacy and
specificity, and tissue distribution of GO conjugates. Flow cytometry and
fluorescence microscopy examination confirmed the targeting specificity of FSHR
mAb attached GO conjugates against cellular FSHR. More potent and persistent
uptake of (64)Cu-NOTA-GO-FSHR-mAb in cbgLuc-MDA-MB-231 nodules inside the lung
was witnessed when compared with that of non-targeted GO conjugates ((64)Cu-NOTA
GO). Histology evaluation also confirmed the vasculature accumulation of GO-FSHR
mAb conjugates in tumor at early time points while they were non-specifically
captured in liver and spleen. In addition, these GO conjugates can serve as good
drug carriers with satisfactory drug loading capacity (e.g. for doxorubicin
[DOX], 756 mg/g). Enhanced drug delivery efficiency in cbgLuc-MDA-MB-231
metastatic sites was demonstrated in DOX-loaded GO-FSHR-mAb by fluorescence
imaging. This FSHR-targeted, GO-based nanoplatform can serve as a useful tool for
early metastasis detection and targeted delivery of therapeutics.
PMID- 27490487
TI - Predicting Molecular Crowding Effects in Ion-RNA Interactions.
AB - We develop a new statistical mechanical model to predict the molecular crowding
effects in ion-RNA interactions. By considering discrete distributions of the
crowders, the model can treat the main crowder-induced effects, such as the
competition with ions for RNA binding, changes of electrostatic interaction due
to crowder-induced changes in the dielectric environment, and changes in the
nonpolar hydration state of the crowder-RNA system. To enhance the computational
efficiency, we sample the crowder distribution using a hybrid approach: For
crowders in the close vicinity of RNA surface, we sample their discrete
distributions; for crowders in the bulk solvent away from the RNA surface, we use
a continuous mean-field distribution for the crowders. Moreover, using the
tightly bound ion (TBI) model, we account for ion fluctuation and correlation
effects in the calculation for ion-RNA interactions. Applications of the model to
a variety of simple RNA structures such as RNA helices show a crowder-induced
increase in free energy and decrease in ion binding. Such crowding effects tend
to contribute to the destabilization of RNA structure. Further analysis indicates
that these effects are associated with the crowder-ion competition in RNA binding
and the effective decrease in the dielectric constant. This simple ion effect
model may serve as a useful framework for modeling more realistic crowders with
larger, more complex RNA structures.
PMID- 27490488
TI - IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING FEATURES OF A MULTIFOCAL
OLIGODENDROGLIOMA IN THE SPINAL CORD AND BRAIN OF A DOG.
AB - An 8-year-old neutered male Toy Poodle was presented with chronic, progressive
tetraparesis, and possible seizures. Magnetic resonance images demonstrated an
extensive, T1 and T2 hyperintense contrast enhancing mass in the cervical spinal
cord. Three nodules were present on the surface of the thalamus, with enhancement
most evident on delayed images. A diagnosis of high-grade oligodendroglioma was
confirmed with postmortem histopathology and immunohistochemical labeling.
Oligodendroglioma should be considered as a differential for T1 hyperintense
intraaxial or intramedullary lesions with contrast enhancement. If enhancement is
not visualized on postcontrast images, delayed images may be beneficial.
PMID- 27490489
TI - Binuclear Complexes and Extended Chains Featuring Pt(II)-Tl(I) Bonds: Influence
of the Pyridine-2-Thiolate and Cyclometalated Ligands on the Self-Assembly and
Luminescent Behavior.
AB - Platinum solvate complexes [Pt(C6F5)(C^N)(S)] [C^N = phenylpyridinyl (ppy), S =
dimethyl sulfoxide (DMSO) (A); C^N = benzoquinolinyl (bzq), S = CH3COCH3 (B)]
react with [Tl(Spy)] (Spy = 2-pyridinethiolate) to afford binuclear
[{Pt(C6F5)(C^N)}Tl(Spy)] [C^N = ppy (1) and bzq (2)] species containing a Pt-Tl
bonding interaction, supported by a MU-Spy-kappaN,S bridging ligand, as confirmed
by X-ray diffraction. However, the related reactions with [Tl(SpyCF3-5)] [SpyCF3
5 = 5-(trifluoromethyl)-2-pyridinethiolate] give neutral extended chains
[{Pt(C6F5)(C^N)}Tl(SpyCF3-5)]n [C^N = ppy (3) and bzq (4)]. 3 features a zigzag
Pt-Tl...S-Pt- chain, generated by Pt-Tl and Tl...S bonds, with the SpyCF3 acting
as a MU-kappaN:kappa(2)S bridging ligand, whereas 4 displays an unsupported ...Tl
Pt...Tl-Pt... backbone (angle of ca. 158.7 degrees ). The lowest-energy
absorption bands in the UV-vis spectra in CH2Cl2, associated with (1)L'LCT
transitions with minor (1)LC/(1)MLCT (L' = Spy or SpyCF3-5; L = C^N) character,
are similar for all complexes 1-4, demonstrating that for 3 and 4 the chains
break down in solution to yield similar bimetallic Pt-Tl units. For 2, two
different forms, 2-o (orange) and 2-y (yellow), exhibiting different colors and
emissions were found depending on the isolation conditions. Slow crystallization
favors formation of the thermodynamically more stable yellow form (2-y), which
exhibits a high-energy (HE) structured emission band, whereas fast
crystallization gives rise to the orange form (2-o), with a remarkably lower
energy structureless emission. Complexes 1 and 3 exhibit dual luminescence in the
solid state at 298 K: an unstructured low-energy band associated with (3)pipi*
excimeric emission due to pi...pi (C^N) interactions and a more structured HE
band, assigned, with support of density functional theory calculations, to an
intraligand (3)LC (C^N) excited state mixed with some ligand (SPy)/platinum-to
ligand (C^N)(3)[(L' + M)LCT] charge transfer. Chain 4 only shows a HE band at 298
K, attributed to a (3)L'LCT (SpyCF3 -> bzq) excited state mixed with a minor
(3)MLCT/(3)MM'CT (M = Pt; M' = Tl) contribution. At 77 K, the pipi*-stacking
emission is predominant in all complexes, except in the form 2-y. Interestingly,
2-4 exhibit reversible mechanochromic color and luminescence changes, with
remarkable red shift and increased quantum yields, and upon exposure to solvents,
they are restored to their original color and emission. On the basis of powder X
ray diffraction studies, a plausible mechanism of the mechanochromic processes is
proposed, involving reversible crystalline-to-amorphous phase transitions.
PMID- 27490490
TI - Lollipops in the Clinic: Information Dense Mutation Plots for Precision Medicine.
AB - INTRODUCTION: Concise visualization is critical to present large amounts of
information in a minimal space that can be interpreted quickly. Clinical
applications in precision medicine present an important use case due to the time
dependent nature of the interpretations, although visualization is increasingly
necessary across the life sciences. In this paper we describe the Lollipops
software for the presentation of panel or exome sequencing results. Source code
and binaries are freely available at https://github.com/pbnjay/lollipops.
Although other software and web resources exist to produce lollipop diagrams,
these packages are less suited to clinical applications. The demands of precision
medicine require the ability to easily fit into a workflow and incorporate
external information without manual intervention. RESULTS: The Lollipops software
provides a simple command line interface that only requires an official gene
symbol and mutation list making it easily scriptable. External information is
integrated using the publicly available Uniprot and Pfam resources. Heuristics
are used to select the most informative components and condense them for a
concise plot. The output is a flexible Scalable Vector Graphic (SVG) diagram that
can be displayed in a web page or graphic illustration tool. CONCLUSION: The
Lollipops software creates information-dense, publication-quality mutation plots
for automated pipelines and high-throughput workflows in precision medicine. The
automatic data integration enables clinical data security, and visualization
heuristics concisely present knowledge with minimal user configuration.
PMID- 27490491
TI - Mycobacterium tuberculosis DevR/DosR Dormancy Regulator Activation Mechanism:
Dispensability of Phosphorylation, Cooperativity and Essentiality of alpha10
Helix.
AB - DevR/DosR is a well-characterized regulator in Mycobacterium tuberculosis which
is implicated in various processes ranging from dormancy/persistence to drug
tolerance. DevR induces the expression of an ~48-gene dormancy regulon in
response to gaseous stresses, including hypoxia. Strains of the Beijing lineage
constitutively express this regulon, which may confer upon them a significant
advantage, since they would be 'pre-adapted' to the environmental stresses that
predominate during infection. Aerobic DevR regulon expression in laboratory
manipulated overexpression strains is also reported. In both instances, the need
for an inducing signal is bypassed. While a phosphorylation-mediated
conformational change in DevR was proposed as the activation mechanism under
hypoxia, the mechanism underlying constitutive expression is not understood.
Because DevR is implicated in bacterial dormancy/persistence and is a promising
drug target, it is relevant to resolve the mechanistic puzzle of hypoxic
activation on one hand and constitutive expression under 'non-inducing'
conditions on the other. Here, an overexpression strategy was employed to
elucidate the DevR activation mechanism. Using a panel of kinase and
transcription factor mutants, we establish that DevR, upon overexpression,
circumvents DevS/DosT sensor kinase-mediated or small molecule phosphodonor
dependent activation, and also cooperativity-mediated effects, which are key
aspects of hypoxic activation mechanism. However, overexpression failed to rescue
the defect of C-terminal-truncated DevR lacking the alpha10 helix, establishing
the alpha10 helix as an indispensable component of DevR activation mechanism. We
propose that aerobic overexpression of DevR likely increases the concentration of
alpha10 helix-mediated active dimer species to above the threshold level, as
during hypoxia, and enables regulon expression. This advance in the understanding
of DevR activation mechanism clarifies a long standing question as to the
mechanism of DevR overexpression-mediated induction of the regulon in the absence
of the normal environmental cue and establishes the alpha10 helix as an universal
and pivotal targeting interface for DevR inhibitor development.
PMID- 27490493
TI - Psychophysiological Responses to Group Exercise Training Sessions: Does Exercise
Intensity Matter?
AB - Group exercise training programs were introduced as a strategy for improving
health and fitness and potentially reducing dropout rates. This study examined
the psychophysiological responses to group exercise training sessions. Twenty
seven adults completed two group exercise training sessions of moderate and
vigorous exercise intensities in a random and counterbalanced order. The %HRR and
the exertional and arousal responses to vigorous session were higher than those
during the moderate session (p<0.05). Consequently, the affective responses to
vigorous session were less pleasant than those during moderate session (p<0.05).
These results suggest that the psychophysiological responses to group exercise
training sessions are intensity-dependent. From an adherence perspective,
interventionists are encouraged to emphasize group exercise training sessions at
a moderate intensity to maximize affective responses and to minimize exertional
responses, which in turn may positively affect future exercise behavior.
PMID- 27490492
TI - High Frequency and Diversity of Antimicrobial Activities Produced by Nasal
Staphylococcus Strains against Bacterial Competitors.
AB - The human nasal microbiota is highly variable and dynamic often enclosing major
pathogens such as Staphylococcus aureus. The potential roles of bacteriocins or
other mechanisms allowing certain bacterial clones to prevail in this nutrient
poor habitat have hardly been studied. Of 89 nasal Staphylococcus isolates,
unexpectedly, the vast majority (84%) was found to produce antimicrobial
substances in particular under habitat-specific stress conditions, such as iron
limitation or exposure to hydrogen peroxide. Activity spectra were generally
narrow but highly variable with activities against certain nasal members of the
Actinobacteria, Proteobacteria, Firmicutes, or several groups of bacteria.
Staphylococcus species and many other Firmicutes were insusceptible to most of
the compounds. A representative bacteriocin was identified as a nukacin-related
peptide whose inactivation reduced the capacity of the producer Staphylococcus
epidermidis IVK45 to limit growth of other nasal bacteria. Of note, the
bacteriocin genes were found on mobile genetic elements exhibiting signs of
extensive horizontal gene transfer and rearrangements. Thus, continuously
evolving bacteriocins appear to govern bacterial competition in the human nose
and specific bacteriocins may become important agents for eradication of
notorious opportunistic pathogens from human microbiota.
PMID- 27490494
TI - Adaptive local learning in sampling based motion planning for protein folding.
AB - BACKGROUND: Simulating protein folding motions is an important problem in
computational biology. Motion planning algorithms, such as Probabilistic Roadmap
Methods, have been successful in modeling the folding landscape. Probabilistic
Roadmap Methods and variants contain several phases (i.e., sampling, connection,
and path extraction). Most of the time is spent in the connection phase and
selecting which variant to employ is a difficult task. Global machine learning
has been applied to the connection phase but is inefficient in situations with
varying topology, such as those typical of folding landscapes. RESULTS: We
develop a local learning algorithm that exploits the past performance of methods
within the neighborhood of the current connection attempts as a basis for
learning. It is sensitive not only to different types of landscapes but also to
differing regions in the landscape itself, removing the need to explicitly
partition the landscape. We perform experiments on 23 proteins of varying
secondary structure makeup with 52-114 residues. We compare the success rate when
using our methods and other methods. We demonstrate a clear need for learning
(i.e., only learning methods were able to validate against all available
experimental data) and show that local learning is superior to global learning
producing, in many cases, significantly higher quality results than the other
methods. CONCLUSIONS: We present an algorithm that uses local learning to select
appropriate connection methods in the context of roadmap construction for protein
folding. Our method removes the burden of deciding which method to use, leverages
the strengths of the individual input methods, and it is extendable to include
other future connection methods.
PMID- 27490495
TI - Development and validation of a prognostic nomogram for acute-on-chronic
hepatitis B liver failure.
AB - BACKGROUND AND AIM: Determining individual risk of short-term mortality in
patients with acute-on-chronic hepatitis B liver failure (ACHBLF) is a difficult
task. We aimed to develop and externally validate a prognostic nomogram for
ACHBLF patients. METHODS: The nomogram was built to estimate the probability of
30-day, 60-day, 90-day, and 60-month survival based on an internal cohort of 246
patients with ACHBLF. The predictive accuracy and discriminative ability of
nomogram were determined by a concordance index (C-index), calibration curve, and
time-dependent receiver operating characteristics (tdROC), comparing with model
for end-stage liver disease (MELD) score. The results were validated using
bootstrap resampling and an external cohort of 138 patients. Furthermore, we
plotted decision curves to evaluate the clinical usefulness of nomogram. RESULTS:
Independent factors derived from multivariable Cox analysis of training cohort to
predict mortality were age, total bilirubin, serum sodium, and prothrombin
activity, which were all assembled into nomogram. The calibration curves for
probability of survival showed optimal agreement between nomogram prediction and
actual observation. The C-index of nomogram was higher than that of MELD score
for predicting survival (30-day, 0.809 vs 0.717, P < 0.001; 60-day, 0.792 vs
0.685, P < 0.001; 90-day, 0.779 vs 0.678, P < 0.001; 6-month, 0.781 vs 0.677, P <
0.001). Additionally, tdROC and decision curves also showed that nomogram was
superior to MELD score. The results were confirmed in validation cohort.
CONCLUSIONS: The prognostic nomogram provided an individualized risk estimate of
short-term survival in patients with ACHBLF, offering to clinicians to improve
their abilities to assess patient prognosis.
PMID- 27490496
TI - Thermal Cycloisomerization of Putative Allenylpyridines for the Synthesis of
Isoquinoline Derivatives.
AB - A cascade (cyclo)isomerization/elimination process produces novel isoquinoline
derivatives of potential interest for pharmaceutical, biomedical, and energy
related research. Mechanistic experiments support a putative allenylpyridine
(reminiscent of the Garratt-Braverman cyclization) as a key intermediate in the
cascade process.
PMID- 27490497
TI - NMR-Assisted Molecular Docking Methodologies.
AB - Nuclear magnetic resonance (NMR) spectroscopy and molecular docking are regularly
being employed as helpful tools of drug discovery research. Molecular docking is
an extremely rapid method to evaluate possible binders from a large chemical
library in a fast and cheap manner. NMR techniques can directly detect a protein
ligand interaction, can determine the corresponding association constant, and can
consistently identify the ligand binding cavity. Consequently, molecular docking
and NMR techniques are naturally complementary techniques where the combination
of the two has the potential to improve the overall efficiency of drug discovery
process. In this review, we would like to summarize the state of the art of
docking methods which have been recently bridged to NMR experiments to identify
novel and effective therapeutic drug candidates.
PMID- 27490498
TI - Structural Characteristics of the Allosteric Binding Site Represent a Key to
Subtype Selective Modulators of Muscarinic Acetylcholine Receptors.
AB - The high conservation of the orthosteric acetylcholine binding site of muscarinic
receptors (MAChR) represents a considerable challenge in terms of designing
subtype selective drugs. A promising approach to gain subtype selectivity is to
include allosteric or dualsteric targeting that aims to address more specific
extracellular binding sites. Despite recent advances in crystallography of G
protein coupled receptors (GPCRs), structural information for all 5 MAChR
subtypes is not yet available. Here we report structural models of the active and
the inactive receptor state of all subtypes derived by homology modelling in
combination with MD simulations. The comparison of the allosteric binding site
unveils the characteristics for each subtype on a structural level and indicates
anchor points for rational design of selective drugs. Additionally, homology
models offer the possibility for a rational explanation of dualsteric subtype
selectivity, as we show for the M2 over M5 selectivity of the dualsteric ligands
Atr-6-naph and Iper-6-phth.
PMID- 27490499
TI - Method for Systematic Assessment of Chemical Changes in Molecular Scaffolds with
Conserved Topology and Application to the Analysis of Scaffold-Activity
Relationships.
AB - Sets of scaffolds with conserved molecular topology are abundant among drugs and
bioactive compounds. Core structure topology is one of the determinants of
biological activity. Heteroatom replacements and/or bond order variation render
topologically equivalent scaffolds chemically distinct and also contribute to
differences in the biological activity of compounds containing these scaffolds.
Relationships between core structure topology, chemical modifications, and
observed activity profiles are difficult to analyze. A computational method is
introduced to consistently assess chemical transformations that distinguish
scaffolds with conserved topology. The methodology is applied to quantify
chemical differences in conserved topological environments and systematically
relate chemical changes in topologically equivalent scaffolds to associated
activity profiles.
PMID- 27490500
TI - Acceleration of Binding Site Comparisons by Graph Partitioning.
AB - The comparison of protein binding sites is a prominent task in computational
chemistry and has been studied in many different ways. For the automatic
detection and comparison of putative binding cavities the Cavbase system has been
developed which uses a coarse-grained set of pseudocenters to represent the
physicochemical properties of a binding site and employs a graph-based procedure
to calculate similarities between two binding sites. However, the comparison of
two graphs is computationally quite demanding which makes large-scale studies
such as the rapid screening of entire databases hardly feasible. In a recent
work, we proposed the method Local Cliques (LC) for the efficient comparison of
Cavbase binding sites. It employs a clique heuristic to detect the maximum common
subgraph of two binding sites and an extended graph model to additionally compare
the shape of individual surface patches. In this study, we present an alternative
to further accelerate the LC method by partitioning the binding-site graphs into
disjoint components prior to their comparisons. The pseudocenter sets are split
with regard to their assigned phyiscochemical type, which leads to seven much
smaller graphs than the original one. Applying this approach on the same test
scenarios as in the former comprehensive way results in a significant speed-up
without sacrificing accuracy.
PMID- 27490501
TI - Identification and Validation Novel of VIM-2 Metallo-beta-lactamase Tripeptide
Inhibitors.
AB - The development of novel inhibitors against metallo-beta-lactamase is essential
to remedy metallo-beta-lactamase mediated bacterial resistance. A recently
emerged metallo-beta-lactamase, VIM-2, has demonstrated resistance to existing
beta-lactamase inhibitors in the clinic. In this study, a hybrid virtual
screening protocol that combines pharmacophore modeling, molecular docking, and
calculation of binding free energy was employed to screen an internal tripeptide
database for novel inhibitors against VIM-2. This resulted in four tripeptides
(WWC, WCW, MCW, YCW) as potential inhibitors, and their effects on VIM-2 metallo
beta-lactamase were subsequently tested in vitro. Significantly, two peptides
(MCW, YCW) exhibited potent inhibitory activities with IC50 values of 18.15 uM
and 52.9 uM, respectively. To our knowledge, this is the first study that
employed the hybrid virtual screening of combinational peptide database and
discovered potent peptide inhibitors of VIM-2 metallo-beta-lactamase.
PMID- 27490502
TI - Cross-Mapping of Protein - Ligand Binding Data Between ChEMBL and PDBbind.
AB - The ChEMBL database is a valuable open data source, which provides a
comprehensive collection of binding data, functional and ADMET properties of
bioactive compounds. The PDBbind database has a more focused scope, i.e.
collecting binding data for the protein-ligand complexes in the Protein Data
Bank. Currently, the PDBbind collection of binding data is rather modest as
compared to the ChEMBL collection (~13 000 versus ~1.3 million). One may suspect
if the former is actually a subset of the latter. In this study, we mapped the
molecular information and protein-ligand binding data in PDBbind to the records
in ChEMBL, and then analyzed the overlap between the binding data recorded in
these two databases. Our results indicate that only ~20 % of the binding data in
PDBbind can find their counterparts in ChEMBL. Thus, the PDBbind collection of
binding data is largely complementary to the ChEMBL collection. We also reveal
two reasons accounting for the low overlap between two databases: First, only a
minor fraction of the protein-ligand complexes in PDBbind is covered by ChEMBL;
Second, the literature spaces screened by these two databases do not have a
substantial overlap either. The value of focused databases versus more
comprehensive ones is demonstrated by our study.
PMID- 27490503
TI - Design Evolution of the Glenoid Component in Total Shoulder Arthroplasty.
PMID- 27490504
TI - Limited Arthroplasty for Osteoarthritis of the Knee: A Critical Analysis Review.
PMID- 27490505
TI - Blood Management for Patients Undergoing Total Joint Arthroplasty.
PMID- 27490506
TI - Injectable Collagenase for the Treatment of Dupuytren Contracture: A Critical
Analysis Review.
PMID- 27490507
TI - The Effect of Articular Reduction After Fractures on Posttraumatic Degenerative
Arthritis: A Critical Analysis Review.
PMID- 27490508
TI - Failed Total Knee Arthroplasty.
PMID- 27490509
TI - An Introduction to the Linear Mixed Model for Orthopaedic Research.
PMID- 27490510
TI - Endoscopic Treatment of Greater Trochanteric Pain Syndrome of the Hip.
PMID- 27490511
TI - Management of Syndesmotic Disruption in Ankle Fractures: A Critical Analysis
Review.
PMID- 27490512
TI - Tenodesis of the Long Head of the Biceps: A Review of Indications, Techniques,
and Outcomes.
PMID- 27490513
TI - Prevalence of Amyotrophic Lateral Sclerosis - United States, 2012-2013.
AB - PROBLEM/CONDITION: Amyotrophic lateral sclerosis (ALS), commonly known as Lou
Gehrig's disease, is a progressive and fatal neuromuscular disease for which no
cure or viable treatment has been identified. ALS, like most noncommunicable
diseases, is not a nationally notifiable disease in the United States. The
prevalence of ALS in the United States during 2010-2011 was estimated to be 3.9
cases per 100,000 persons in the general population. Updated prevalence estimates
are needed to help monitor disease status, better understand etiology, and
identify risk factors for ALS. PERIOD COVERED: 2012-2013. DESCRIPTION OF SYSTEM:
The National ALS Registry, established in 2009, collects data on ALS patients in
the United States to better describe the incidence and prevalence of ALS, examine
risk factors such as environmental and occupational exposures, and characterize
the demographics of those living with ALS. To identify prevalent cases of ALS,
data are compiled from four national administrative databases (maintained by the
Centers for Medicare and Medicaid Services, the Veterans Health Administration,
and the Veterans Benefits Administration). To identify cases not included in
these databases and to better understand risk-factors associated with ALS and
disease progression, the Registry also includes data that are collected from
patients who voluntarily enroll and complete online surveys. RESULTS: During 2012
and 2013, the Registry identified 14,713 and 15,908 persons, respectively, who
met the surveillance case definition of ALS. The estimated ALS prevalence rate
was 4.7 cases per 100,000 U.S. population for 2012 and 5.0 per 100,000 for 2013.
Due to revisions to the algorithm and use of death data from the National Death
Index, an updated prevalence estimate has been calculated retrospectively for
October 19, 2010-December 31, 2011. This updated estimate showed a prevalence
rate of 4.3 per 100,000 population and a total of 13,282 cases. Since the
inception of the Registry, the pattern of characteristics (e.g., age, sex, and
race/ethnicity) among persons with ALS have remained unchanged. Overall, ALS was
more common among whites, males, and persons aged 60-69 years. The age groups
with the lowest number of ALS cases were persons aged 18-39 years and those aged
>=80 years. Males had a higher prevalence rate of ALS than females overall and
across all data sources. These findings remained consistent during October 2010
December 2013. INTERPRETATION: The Registry is the only available data source
that can be used to estimate the national prevalence for ALS in the United
States. Use of both administrative national databases and self-report from
patients enables a comprehensive approach to estimate ALS prevalence. The overall
increase in the prevalence rate from 4.3 per 100,000 persons (revised) during
2010-2011 to 4.7 and 5.0 per 100,000 persons, respectively, during 2012-2013
likely is not an actual increase in the number of ALS cases. Rather, this
increase might be attributed to improved case ascertainment due to the refinement
of the algorithm used to identify definite ALS cases, along with an increased
public awareness of the Registry. Registry estimates of ALS prevalence are
consistent with findings from long-established ALS registries in Europe and from
smaller-scale epidemiologic studies previously conducted in the United States.
PUBLIC HEALTH ACTIONS: Data collected by the National ALS Registry are being used
to better describe the epidemiology of ALS in the United States and to help
facilitate research. The combined approach of using national administrative
databases and a self-enrollment web portal to collect data is novel and
potentially could be used for other non-notifiable diseases such as Parkinson's
disease or multiple sclerosis. Increased public awareness of the Registry might
lead to more ALS cases being identified from the secure web portal
(https://www.cdc.gov/als), which can ascertain cases apart from the national
administrative databases. For example, in 2014, the ALS Ice Bucket Challenge, a
social media-centered campaign, received extensive public visibility and created
increased awareness of ALS. The Agency for Toxic Substances and Disease Registry
(ATSDR) works closely with ALS advocacy and support groups, researchers, health
care professionals, and others to promote the National ALS Registry and to
identify all cases of ALS in the United States. In addition to estimating the
prevalence of ALS, the Registry is being used to collect specimens from patient
enrollees through a new biorepository, connect patient enrollees with new
clinical trials and epidemiologic studies, and fund studies to help learn more
about the etiology of ALS. Additional information about the National ALS Registry
is available at http://www.cdc.gov/als or by calling toll-free at 1-877-442-9719.
PMID- 27490514
TI - Medical and Surgical Treatments for Usual-Type Vulvar Intraepithelial Neoplasia.
AB - Clinical Question: Which interventions are the most effective and tolerable for
treating usual-type vulvar intraepithelial neoplasia? Bottom Line: Provided
cancer is not suspected, usual-type vulvar intraepithelial neoplasia treatment,
including medical and surgical options, can be individualized to take into
account the site, extent of disease, and a woman's preferences, with a commitment
to long-term follow-up.
PMID- 27490515
TI - Childhood emotional maltreatment and mental disorders: Results from a nationally
representative adult sample from the United States.
AB - Child maltreatment is a public health concern with well-established sequelae.
However, compared to research on physical and sexual abuse, far less is known
about the long-term impact of emotional maltreatment on mental health. The
overall purpose of this study was to examine the association of emotional abuse,
emotional neglect, and both emotional abuse and neglect with other types of child
maltreatment, a family history of dysfunction, and lifetime diagnoses of several
Axis I and Axis II mental disorders. Data were from the National Epidemiological
Survey on Alcohol and Related Conditions collected in 2004 and 2005 (n=34,653).
The most prevalent form of emotional maltreatment was emotional neglect only
(6.2%), followed by emotional abuse only (4.8%), and then both emotional abuse
and neglect (3.1%). All categories of emotional maltreatment were strongly
related to other forms of child maltreatment (odds ratios [ORs] ranged from 2.1
to 68.0) and a history of family dysfunction (ORs ranged from 2.2 to 8.3). In
models adjusting for sociodemographic characteristics, all categories of
emotional maltreatment were associated with increased odds of almost every mental
disorder assessed in this study (adjusted ORs ranged from 1.2 to 7.4). Many
relationships remained significant independent of experiencing other forms of
child maltreatment and a family history of dysfunction (adjusted ORs ranged from
1.2 to 3.0). The effects appeared to be greater for active (i.e., emotional
abuse) relative to passive (i.e., emotional neglect) forms of emotional
maltreatment. Childhood emotional maltreatment, particularly emotionally abusive
acts, is associated with increased odds of lifetime diagnoses of several Axis I
and Axis II mental disorders.
PMID- 27490516
TI - Is there a role for paediatric Sexual Assault Nurse Examiners in the management
of child sexual assault in Australia?
AB - In Australia, paediatricians and Child Protection Specialists provide the medical
and forensic examinations of child victims of sexual assault. There are workforce
challenges in the recruitment and retention of doctors to undertake child sexual
assault (CSA) work particularly in remote and rural areas. Pediatric Sexual
Assault Nurse Examiner (PSANE) programs have existed in the USA and the UK for
many years. Using Rapid Evidence Assessment (REA) methodology, a systematic
search of the literature was performed to ascertain what is known about SANE
programs, to evaluate the evidence for their effectiveness across a number of
domains (accessibility, health and legal outcomes and cost effectiveness) and to
inform policy on models of care and elements of best practice which may be
appropriate for local implementation in Australia. This review showed that
despite the limited evidence available and significant gaps in the evidence,
SANEs provide a high standard of medical care and are not detrimental to the
legal process. By providing recommendations regarding the potential value,
effectiveness and feasibility of establishing a PSANE program in Australia, this
article may be of interest to other high income countries facing similar
workforce challenges in meeting the needs of children with alleged sexual
assault.
PMID- 27490517
TI - Exploring child prostitution in a major city in the West African region.
AB - The study explored the characteristics of child prostitution in a major city in
the West African region. A convenience sample of children in prostitution,
specifically girls below age 18 (n=243), were recruited on 83 prostitution sites
identified in Ouagadougou, the capital city of Burkina Faso. A survey instrument,
consisting of 71 closed-ended question items, was used to explore various
variables including profile of children in prostitution, factors of vulnerability
to prostitution; prostitution practices, compensations and related issues in
child prostitution. The findings show that most children in prostitution in the
city were from Burkina Faso (63%) and Nigeria (30%), two countries that do not
share borders. Most native respondents practiced prostitution for survival and to
support their families. In contrast, all the respondents from Nigeria practiced
prostitution as victims of international sex trafficking. An important finding
was that 77% of the children in prostitution surveyed were educated. Among the
respondents, there were similarities in the major life events that contributed to
their situation of prostitution. These life events include early separation with
parents, sexual abuse, foster care, and forced marriage. Implications for policy,
practice and research are discussed.
PMID- 27490518
TI - Self-Powered Triboelectric Micro Liquid/Gas Flow Sensor for Microfluidics.
AB - Liquid and gas flow sensors are important components of the micro total analysis
systems (MUTAS) for modern analytical sciences. In this paper, we proposed a self
powered triboelectric microfluidic sensor (TMS) by utilizing the signals produced
from the droplet/bubble via the capillary and the triboelectrification effects on
the liquid/solid interface for real-time liquid and gas flow detection. By
alternating capillary with different diameters, the sensor's detecting range and
sensitivity can be adjusted. Both the relationship between the droplet/bubble and
capillary size, and the output signal of the sensor are systematically studied.
By demonstrating the monitoring of the transfusion process for a patient and the
gas flow produced from an injector, it shows that TMS has a great potential in
building a self-powered micro total analysis system.
PMID- 27490520
TI - Ultrasensitive Strain Sensor Produced by Direct Patterning of Liquid Crystals of
Graphene Oxide on a Flexible Substrate.
AB - Ultrasensitive flexible strain sensors were developed through the combination of
shear alignment of a high concentration graphene oxide (GO) dispersion with fast
and precise patterning of multiple rectangular features on a flexible substrate.
Resistive changes in the reduced GO films were investigated under various
uniaxial strain cycles ranging from 0.025 to 2%, controlled with a motorized
nanopositioning stage. The devices uniquely combine a very small detection limit
(0.025%) and a high gauge factor with a rapid fabrication process conducive to
batch production.
PMID- 27490519
TI - Human Proteome Project Mass Spectrometry Data Interpretation Guidelines 2.1.
AB - Every data-rich community research effort requires a clear plan for ensuring the
quality of the data interpretation and comparability of analyses. To address this
need within the Human Proteome Project (HPP) of the Human Proteome Organization
(HUPO), we have developed through broad consultation a set of mass spectrometry
data interpretation guidelines that should be applied to all HPP data
contributions. For submission of manuscripts reporting HPP protein identification
results, the guidelines are presented as a one-page checklist containing 15
essential points followed by two pages of expanded description of each. Here we
present an overview of the guidelines and provide an in-depth description of each
of the 15 elements to facilitate understanding of the intentions and rationale
behind the guidelines, for both authors and reviewers. Broadly, these guidelines
provide specific directions regarding how HPP data are to be submitted to mass
spectrometry data repositories, how error analysis should be presented, and how
detection of novel proteins should be supported with additional confirmatory
evidence. These guidelines, developed by the HPP community, are presented to the
broader scientific community for further discussion.
PMID- 27490521
TI - Correlation study between image features and mechanical properties of Han Chinese
facial skin.
AB - OBJECTIVE: Mechanical properties are considered to be vital factors that
influence skin physiology during ageing. Wrinkles and skin roughness are the two
main features in aged skin. The purpose of this study is to characterize the
relationship between facial skin mechanical properties and image features using
quantitative methods. METHODS: Two hundred and forty healthy male and female
volunteers living in Shanghai, China (aged 20-70 years), were examined in this
study. Facial images were photographed by VISIA-CR. Wrinkle volume of middle
forehead and skin roughness of upper cheek were analysed by Skin Surface Analyzer
(SSA) software. Mechanical parameters at the middle forehead and upper cheek were
measured using Cutometer(r) MPA 580 and Reviscometer(r) RVM 600. RESULTS: Skin
wrinkles and roughness increased during ageing, where men have a higher level and
earlier manifestation than women. Skin mechanical parameters R2, R5, R7 and RRT
were found decreased with age. Moreover, mechanical parameters including R2, R7,
RRT and anisotropy showed significant correlations with wrinkle volume and/or
skin roughness. CONCLUSION: The facial image features including wrinkle volume
and skin roughness are significantly correlated with skin elasticity and
anisotropy, which could well describe the skin features of Han Chinese.
PMID- 27490522
TI - Intramolecular Chain Hydrosilylation of Alkynylphenylsilanes Using a Silyl Cation
as a Chain Carrier.
AB - Diorganyl[2-(trimethylsilylethynyl)phenyl]silanes 1a-c and methyl-substituted
phenylsilanes 1d and 1e were treated with a small amount of trityl
tetrakis(pentafluorophenyl)borate (TPFPB) as an initiator in benzene to afford
the corresponding benzosiloles (2a-e) in moderate to good yields. However, no
reaction was observed for the reaction using [2-(1
hexynyl)phenyl]diisopropylsilane lf. The methyl substituent was tolerated under
the reaction conditions and increased the yield of the corresponding benzosilole
depending on the substitution position. From the result using 1f, the current
reaction was found to require the trimethylsilyl group, which can stabilize
intermediary alkenyl carbocations by the beta-silyl effect. The current reaction
can be considered an intramolecular chain hydrosilylation of alkynylarylsilanes
involving silyl cations as chain carriers. Therefore, the silyl cations generated
by hydride abstraction from hydrosilanes 1 with the trityl cation causes
intramolecular electrophilic addition to the C-C triple bond to form ethenyl
cations, which abstract a hydride from 1 to afford benzosiloles 2 with the
regeneration of the silyl cations.
PMID- 27490523
TI - Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive
Agents.
AB - In the current work, new 1,3,4-thiadiazole derivatives were synthesized and
investigated for their antinociceptive effects on nociceptive pathways of nervous
system. The effects of these compounds against mechanical, thermal and chemical
stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing
tests, respectively. In addition, activity cage was performed to assess the
locomotor activity of animals. The obtained data indicated that compounds 3b, 3c,
3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and
tail-clip tests, indicating the centrally mediated antinociceptive activity of
these compounds. Additionally, the number of writhing behavior was significantly
decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out
the peripherally mediated antinociceptive activity induced by these four
compounds. According to the activity cage tests, compounds 3a, 3c and 3f
significantly decreased both horizontal and vertical locomotor activity of mice.
Antinociceptive behavior of these three compounds may be non-specific and caused
by possible sedative effect or motor impairments.
PMID- 27490524
TI - In Vivo Monitoring of the Growth of Fertilized Eggs of Medaka Fish (Oryzias
latipes) by Near-Infrared Spectroscopy and Near-Infrared Imaging-A Marked Change
in the Relative Content of Weakly Hydrogen-Bonded Water in Egg Yolk Just before
Hatching.
AB - The present study develops further our previous study of in vivo monitoring at
the molecular level of the embryonic development in Japanese medaka fish (Oryzias
latipes) using near-infrared (NIR) spectroscopy and NIR imaging. NIR spectra were
measured nondestructively for three major parts of fertilized medaka eggs (the
embryonic body, oil droplets, and egg yolk) from the first day after
fertilization to the day just before hatching (JBH). Changes in the contents of
chemical components such as proteins, water, and lipids were monitored in situ
during embryonic development. A marked change in the relative content of weakly
hydrogen-bonded water was observed in the egg yolk JBH. Principal component
analysis (PCA) was carried out using the NIR spectra data of the egg yolk and
embryo on the fifth day after fertilization. The PCA clearly separates the egg
yolk data from the embryo body parts. Principal component PC1 and PC2 loading
plots suggest that the hydrogen bonding structure of water in the egg yolk is
considerably different to those of the other parts and the fraction of weakly
hydrogen-bonded water in the egg yolk is smaller than that in the embryonic body.
NIR images developed from the intensities of peaks of second derivative spectra
owing to water and proteins show their different distribution patterns. Images of
the ratio of strongly and weakly hydrogen-bonded water confirmed that oil
droplets and embryonic body parts have higher and lower ratios, respectively, of
strongly hydrogen-bonded water than do the other parts. The images developed from
the intensity of the peaks at 4864 and 4616 cm(-1) related to the proteins
indicated that the egg yolk contains a higher concentration of protein than do
the other parts. The peaks at 5756 and 4530 cm(-1) caused by the protein
secondary structures of alpha-helix and beta-sheet showed the configuration of
the egg cell membrane. The present study might lead to new understanding at the
molecular level regarding the growth of fertilized eggs and provides a new tool
to visualize egg development in a nondestructive manner.
PMID- 27490525
TI - Microfluidic Devices in Advanced Caenorhabditis elegans Research.
AB - The study of model organisms is very important in view of their potential for
application to human therapeutic uses. One such model organism is the nematode
worm, Caenorhabditis elegans. As a nematode, C. elegans have ~65% similarity with
human disease genes and, therefore, studies on C. elegans can be translated to
human, as well as, C. elegans can be used in the study of different types of
parasitic worms that infect other living organisms. In the past decade, many
efforts have been undertaken to establish interdisciplinary research
collaborations between biologists, physicists and engineers in order to develop
microfluidic devices to study the biology of C. elegans. Microfluidic devices
with the power to manipulate and detect bio-samples, regents or biomolecules in
micro-scale environments can well fulfill the requirement to handle worms under
proper laboratory conditions, thereby significantly increasing research
productivity and knowledge. The recent development of different kinds of
microfluidic devices with ultra-high throughput platforms has enabled researchers
to carry out worm population studies. Microfluidic devices primarily comprises of
chambers, channels and valves, wherein worms can be cultured, immobilized,
imaged, etc. Microfluidic devices have been adapted to study various worm
behaviors, including that deepen our understanding of neuromuscular connectivity
and functions. This review will provide a clear account of the vital involvement
of microfluidic devices in worm biology.
PMID- 27490526
TI - Agavins Increase Neurotrophic Factors and Decrease Oxidative Stress in the Brains
of High-Fat Diet-Induced Obese Mice.
AB - BACKGROUND: Fructans obtained from agave, called agavins, have recently shown
significant benefits for human health including obesity. Therefore, we evaluated
the potential of agavins as neuroprotectors and antioxidants by determining their
effect on brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic
factor (GDNF) as well as oxidative brain damage in of obese mice. METHODS: Male
C57BL/6J mice were fed a high-fat diet (HFD) and treated daily with 5% (HFD/A5)
or 10% (HFD/A10) of agavins or a standard diet (SD) for 10 weeks. The levels of
BDNF and GDNF were evaluated by ELISA. The oxidative stress was evaluated by
lipid peroxidation (TBARS) and carbonyls. SCFAs were also measured with GC-FID.
Differences between groups were assessed using ANOVA and by Tukey's test
considering p < 0.05. RESULTS: The body weight gain and food intake of mice
HFD/A10 group were significantly lower than those in the HFD group. Agavins
restored BDNF levels in HFD/A5 group and GDNF levels of HFD/A5 and HFD/A10 groups
in cerebellum. Interestingly, agavins decreased TBARS levels in HFD/A5 and
HFD/A10 groups in the hippocampus, frontal cortex and cerebellum. Carbonyl levels
were also lower in HFD/A5 and HFD/A10 for only the hippocampus and cerebellum. It
was also found that agavins enhanced SCFAs production in feces. CONCLUSION:
Agavins may act as bioactive ingredients with antioxidant and protective roles in
the brain.
PMID- 27490527
TI - Potential Application of p-Coumaric Acid on Differentiation of C2C12 Skeletal
Muscle and 3T3-L1 Preadipocytes-An in Vitro and in Silico Approach.
AB - Coumaric acid (CA) is a phenolic acid of the hydroxycinnamic acid family, and it
has many biological functions such as anti-oxidant, anti-inflammatory,
antidiabetic, anti-ulcer, anti-platelet, anti-cancer activities, etc. In the
present study, we planned to analyse the potential molecular function of CA on
skeletal muscle and preadipocytes differentiation using PCR and Western blot
techniques. First, we analysed the impact of CA on C2C12 skeletal muscle
differentiation. It revealed that CA treatment inhibited horse serum-induced
skeletal muscle differentiation as evidenced by the decreased expression of early
myogenic differentiation markers such as Myogenin and myoD via the AMP activated
protein kinase- alpha AMPK-alpha mediated pathway. Furthermore, the level of
lipid accumulation and changes in genes and protein expressions that are
associated with lipogenesis and lipolysis were analyzed in 3T3-L1 cells. The Oil
Red O staining evidenced that CA treatment inhibited lipid accumulation at the
concentration of 0.1 and 0.2 mM. Furthermore, coumaric acid treatment decreased
the expression of main transcriptional factors such as CCAAT/enhancer binding
protein-alpha (C/EBP-alpha) and peroxisome proliferator-activated receptor gamma
2 (PPAR-gamma2). Subsequently, CA treatment decreased the expression of sterol
regulatory element binding protein-1 (SREBP-1), fatty acid synthase (FAS), acetyl
CoA carboxylase (ACC) and adiponectin. Finally, we identified conformational
changes induced by CA in PPAR-gamma2 using computational biology tools. It
revealed that CA might downregulate the PPAR-gamma2 expression by directly
binding with amino acids of PPAR-gamma2 by hydrogen at 3.26 distance and
hydrophobic interactions at 3.90 contact distances. These data indicated that CA
suppressed skeletal muscle and preadipocytes differentiation through
downregulation of the main transcriptional factors and their downstream targets.
PMID- 27490528
TI - Effects on Nitric Oxide Production of Urolithins, Gut-Derived Ellagitannin
Metabolites, in Human Aortic Endothelial Cells.
AB - The consumption of foodstuffs yielding circulating compounds able to maintain
endothelial function by improving nitric oxide (NO) bioavailability can be
considered as an effective strategy for cardiovascular disease prevention. This
work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B
glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release
and endothelial NO synthase (eNOS) activation in primary human aortic endothelial
cells (HAECs). Urolithins were tested both individually at 15 MUM and as a
mixture of 5 MUM each, at different time points. The biotransformation of these
molecules in cell media due to cell metabolism was also evaluated by UHPLC-MS(n).
The mix of urolithins at 5 MUM significantly increased nitrite/nitrate levels
following 24 h of incubation, while single urolithins at 15 MUM did not modify NO
bioavailability. Both the mix of urolithins at 5 MUM and urolithin B-glucuronide
at 15 MUM activated eNOS expression. All urolithins underwent metabolic
reactions, but these were limited to conjugation with sulfate moieties. This
study represents a step forward in the understanding of cardiovascular health
benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells
may contribute to urolithin metabolism.
PMID- 27490529
TI - In Vivo Release Kinetics and Antibacterial Activity of Novel Polyphenols-Enriched
Chewing Gums.
AB - Chewing gums may be particularly effective means for delivering and maintaining
bioactive molecules, included in the gum formulation, able to have an anti
cariogenic effect. The purposes of this study were: to develop novel chewing gums
containing quercetin (Qt); to evaluate their release using in vivo trial;
finally, to test their in vivo antibacterial effect against oral Streptococcus
mutans strains. A preliminary study was performed to produce new gums, enriched
with the polyphenol quercetin. Then, a first in vivo experimental study was
assessed to test the percentages of Qt released in the saliva of young
volunteers. Moreover, a second clinical trial was performed to analyze the
antibacterial capability of these enriched chewing gums against S. mutans strains
after 14 days of daily consumption. The release analysis showed that a more
effective release of Qt occurs in the first minutes of chewing, and it does not
change saliva pH values. Moreover, Qt included in gums demonstrates an effective
antibacterial activity, showing a reduction of the concentration of S. mutans
strains in saliva samples, especially after 7 days. Qt included in experimental
chewing gums could be efficiently released into the oral cavity and could promote
an effective anti-caries concentration in volunteer's saliva, without changing
salivary pH values.
PMID- 27490530
TI - Preparation of Hydrochlorothiazide Nanoparticles for Solubility Enhancement.
AB - Nanoparticles can be considered as a useful tool for improving properties of
poorly soluble active ingredients. Hydrochlorothiazide (Class IV of the
Biopharmaceutical Classification System) was chosen as a model compound.
Antisolvent precipitation-solvent evaporation and emulsion solvent evaporation
methods were used for preparation of 18 samples containing hydrochlorothiazide
nanoparticles. Water solutions of surfactants sodium dodecyl sulfate, Tween 80
and carboxymethyl dextran were used in mass concentrations of 1%, 3% and 5%.
Acetone and dichloromethane were used as solvents of the model compound. The
particle size of the prepared samples was measured by dynamic light scattering.
The selected sample of hydrochlorothiazide nanoparticles stabilized with
carboxymethyl dextran sodium salt with particle size 2.6 nm was characterized
additionally by Fourier transform mid-infrared spectroscopy and scanning electron
microscopy. It was found that the solubility of this sample was 6.5-fold higher
than that of bulk hydrochlorothiazide.
PMID- 27490531
TI - Circulating Organ-Specific MicroRNAs Serve as Biomarkers in Organ-Specific
Diseases: Implications for Organ Allo- and Xeno-Transplantation.
AB - Different cell types possess different miRNA expression profiles, and
cell/tissue/organ-specific miRNAs (or profiles) indicate different diseases.
Circulating miRNA is either actively secreted by living cells or passively
released during cell death. Circulating cell/tissue/organ-specific miRNA may
serve as a non-invasive biomarker for allo- or xeno-transplantation to monitor
organ survival and immune rejection. In this review, we summarize the proof of
concept that circulating organ-specific miRNAs serve as non-invasive biomarkers
for a wide spectrum of clinical organ-specific manifestations such as liver
related disease, heart-related disease, kidney-related disease, and lung-related
disease. Furthermore, we summarize how circulating organ-specific miRNAs may have
advantages over conventional methods for monitoring immune rejection in organ
transplantation. Finally, we discuss the implications and challenges of applying
miRNA to monitor organ survival and immune rejection in allo- or xeno
transplantation.
PMID- 27490533
TI - Coordination Environment of Cu(II) Ions Bound to N-Terminal Peptide Fragments of
Angiogenin Protein.
AB - Angiogenin (Ang) is a potent angiogenic factor, strongly overexpressed in
patients affected by different types of cancers. The specific Ang cellular
receptors have not been identified, but it is known that Ang-actin interaction
induces changes both in the cell cytoskeleton and in the extracellular matrix.
Most in vitro studies use the recombinant form (r-Ang) instead of the form that
is normally present in vivo ("wild-type", wt-Ang). The first residue of r-Ang is
a methionine, with a free amino group, whereas wt-Ang has a glutamic acid, whose
amino group spontaneously cyclizes in the pyro-glutamate form. The Ang biological
activity is influenced by copper ions. To elucidate the role of such a free amino
group on the protein-copper binding, we scrutinized the copper(II) complexes with
the peptide fragments Ang(1-17) and AcAng(1-17), which encompass the sequence 1
17 of angiogenin (QDNSRYTHFLTQHYDAK-NH2), with free amino and acetylated N
terminus, respectively. Potentiometric, ultraviolet-visible (UV-vis), nuclear
magnetic resonance (NMR) and circular dichroism (CD) studies demonstrate that the
two peptides show a different metal coordination environment. Confocal microscopy
imaging of neuroblastoma cells with the actin staining supports the spectroscopic
results, with the finding of different responses in the cytoskeleton organization
upon the interaction, in the presence or not of copper ions, with the free amino
and the acetylated N-terminus peptides.
PMID- 27490532
TI - Serum Concentrations of Endothelin-1 and Matrix Metalloproteinases-2, -9 in Pre
Hypertensive and Hypertensive Patients with Type 2 Diabetes.
AB - Endothelin-1 (ET-1) is one of the most potent vasoconstrictors known to date.
While its plasma or serum concentrations are elevated in some forms of
experimental and human hypertension, this is not a consistent finding in all
forms of hypertension. Matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9),
which degrade collagen type IV of the vascular basement membrane, are responsible
for vascular remodeling, inflammation, and atherosclerotic complications,
including in type 2 diabetes (T2D). In our study, we compared concentrations of
ET-1, MMP-2, and MMP-9 in pre-hypertensive (PHTN) and hypertensive (HTN) T2D
patients with those of healthy normotensive controls (N). ET-1, MMP-2, and MMP-9
were measured by ELISA. Concentrations of ET-1 in PHTN and N were very similar,
while those in HTN were significantly higher. Concentrations of MMP-2 and MMP-9
in PHTN and HTN were also significantly higher compared to N. An interesting
result in our study is that concentrations of MMP-2 and MMP-9 in HTN were lower
compared to PHTN. In conclusion, we showed that increased production of ET-1 in
patients with T2D can lead to long-lasting increases in blood pressure (BP) and
clinical manifestation of hypertension. We also demonstrated that increased
levels of MMP-2 and MMP-9 in pre-hypertensive and hypertensive patients with T2D
mainly reflect the early vascular changes in extracellular matrix (ECM) turnover.
PMID- 27490535
TI - Evaluation of Pulmonary Toxicity of Zinc Oxide Nanoparticles Following Inhalation
and Intratracheal Instillation.
AB - We conducted inhalation and intratracheal instillation studies of zinc oxide
(ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were
received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a
primary diameter of 35 nm that were well-dispersed in distilled water. Cell
analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at
three days, one week, one month, three months, and six months after the
instillation. As the inhalation study, rats were exposed to a concentration of
inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week).
The same endpoints as in the intratracheal instillation study were analyzed at
three days, one month, and three months after the end of the exposure. In the
intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a
transient increase in the total cell and neutrophil count in the BALF and in the
expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2,
chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress
marker, in the BALF. In the inhalation study, transient increases in total cell
and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high
concentration groups. Neither of the studies of ZnO nanoparticles showed
persistent inflammation in the rat lung, suggesting that well-dispersed ZnO
nanoparticles have low toxicity.
PMID- 27490536
TI - Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and
Microbial Translocation in HIV-Infected Children in Vietnam.
AB - CD4+ T-lymphocyte destruction, microbial translocation, and systemic immune
activation are the main mechanisms of the pathogenesis of human immunodeficiency
virus type 1 (HIV) infection. To investigate the impact of HIV infection and
antiretroviral therapy (ART) on the immune profile of and microbial translocation
in HIV-infected children, 60 HIV vertically infected children (31 without ART:
HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(-)) aged 2-12
years were recruited in Vietnam, and their blood samples were immunologically and
bacteriologically analyzed. Among the HIV(+) children, the total CD4+-cell and
their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely
correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and
CD4/CD8 ratios had become lower, and the CD38+HLA (human leukocyte antigen)
DR+CD8+- (activated CD8+) cell percentage and plasma soluble CD14 (sCD14, a
monocyte activation marker) levels had become higher than those of HIV(-)
children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with
the plasma HIV RNA load and CD8+-cell activation status. Among the ART(+)
children, the total CD4+-cell and Th2/Th17/Treg-subset counts and the CD4/CD8
ratio gradually increased, with estimated ART periods of normalization being 4.8
8.3 years, whereas Th1 counts and the CD8+-cell activation status normalized
within 1 year of ART initiation. sCD14 levels remained high even after ART
initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in
blood did not differ between HIV-infected and -uninfected children. Thus, in
children, HIV infection caused a rapid decrease in Treg counts and the early
activation of CD8+ cells and monocytes, and ART induced rapid Th1 recovery and
early CD8+-cell activation normalization but had little effect on monocyte
activation. The CD4/CD8 ratio could therefore be an additional marker for ART
monitoring.
PMID- 27490537
TI - Drought-Induced Leaf Proteome Changes in Switchgrass Seedlings.
AB - Switchgrass (Panicum virgatum) is a perennial crop producing deep roots and thus
highly tolerant to soil water deficit conditions. However, seedling establishment
in the field is very susceptible to prolonged and periodic drought stress. In
this study, a "sandwich" system simulating a gradual water deletion process was
developed. Switchgrass seedlings were subjected to a 20-day gradual drought
treatment process when soil water tension was increased to 0.05 MPa (moderate
drought stress) and leaf physiological properties had expressed significant
alteration. Drought-induced changes in leaf proteomes were identified using the
isobaric tags for relative and absolute quantitation (iTRAQ) labeling method
followed by nano-scale liquid chromatography mass spectrometry (nano-LC-MS/MS)
analysis. Additionally, total leaf proteins were processed using a combinatorial
library of peptide ligands to enrich for lower abundance proteins. Both total
proteins and those enriched samples were analyzed to increase the coverage of the
quantitative proteomics analysis. A total of 7006 leaf proteins were identified,
and 257 (4% of the leaf proteome) expressed a significant difference (p < 0.05,
fold change <0.6 or >1.7) from the non-treated control to drought-treated
conditions. These proteins are involved in the regulation of transcription and
translation, cell division, cell wall modification, phyto-hormone metabolism and
signaling transduction pathways, and metabolic pathways of carbohydrates, amino
acids, and fatty acids. A scheme of abscisic acid (ABA)-biosynthesis and ABA
responsive signal transduction pathway was reconstructed using these drought
induced significant proteins, showing systemic regulation at protein level to
deploy the respective mechanism. Results from this study, in addition to
revealing molecular responses to drought stress, provide a large number of
proteins (candidate genes) that can be employed to improve switchgrass seedling
growth and establishment under soil drought conditions (Data are available via
ProteomeXchange with identifier PXD004675).
PMID- 27490534
TI - The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.
AB - Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs
(AEDs) are always the first choice for treatment. However, more than 50% of
patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome
P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such
as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital
(PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause
vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone
turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as
levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM),
gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and
better tolerated than the classical AEDs. The effects of AEDs on bone health are
controversial. This review focuses on the impact of AEDs on growth and bone
metabolism and emphasizes the need for caution and timely withdrawal of these
medications to avoid serious disabilities.
PMID- 27490538
TI - Association of Serum Uric Acid Concentration with Diabetic Retinopathy and
Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus.
AB - Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular
complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN)
during their lifetime. In clinical studies, serum uric acid concentration has
been found to be associated with DR and DN. The goal of this study was to
evaluate the relationship between the increases in serum uric acid level and the
severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded
serum uric acid concentration, the severity of DR, and the severity of
albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385
patients with type 2 DM. In multivariate logistic regression analysis, a high
uric acid concentration was a risk factor for albuminuria (odds ratio (OR),
1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264;
95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher
concentration of serum uric acid in the patients with more severe albuminuria and
DR. In conclusion, an increased serum uric acid level was significantly
correlated with the severity of albuminuria and DR in Taiwanese patients with
type 2 DM.
PMID- 27490539
TI - Upregulation of Human ST8Sia VI (alpha2,8-Sialyltransferase) Gene Expression by
Physcion in SK-N-BE(2)-C Human Neuroblastoma Cells.
AB - In this research, we firstly demonstrated that physcion, an anthraquinone
derivative, specifically increased the expression of the human alpha2,8
sialyltransferase (hST8Sia VI) gene in SK-N-BE(2)-C human neuroblastoma cells. To
establish the mechanism responsible for the up-regulation of hST8Sia VI gene
expression in physcion-treated SK-N-BE(2)-C cells, the putative promoter region
of the hST8Sia VI gene was functionally characterized. Promoter analysis with
serially truncated fragments of the 5'-flanking region showed that the region
between -320 and -240 is crucial for physcion-induced transcription of hST8Sia VI
in SK-N-BE(2)-C cells. Putative binding sites for transcription factors Pax-5 and
NF-Y are located at this region. The Pax-5 binding site at -262 to -256 was
essential for the expression of the hST8Sia VI gene by physcion in SK-N-BE(2)-C
cells. Moreover, the transcription of hST8Sia VI induced by physcion in SK-N
BE(2)-C cells was inhibited by extracellular signal-regulated protein kinase
(ERK) inhibitor U0126 and p38 mitogen-activated protein kinase (MAPK) inhibitor
SB203580, but not c-Jun N-terminal kinase (JNK) inhibitor SP600125. These results
suggest that physcion upregulates hST8Sia VI gene expression via ERK and p38 MAPK
pathways in SK-N-BE(2)-C cells.
PMID- 27490540
TI - Salvianolic Acid A, as a Novel ETA Receptor Antagonist, Shows Inhibitory Effects
on Tumor in Vitro.
AB - Endothelin-1 (ET-1) autocrine and paracrine signaling modulate cell proliferation
of tumor cells by activating its receptors, endothelin A receptor (ETAR) and
endothelin B receptor (ETBR). Dysregulation of ETAR activation promotes tumor
development and progression. The potential of ETAR antagonists and the dual-ETAR
and ETBR antagonists as therapeutic approaches are under preclinical and clinical
studies. Salvianolic acid A (Sal A) is a hydrophilic polyphenolic derivative
isolated from Salvia miltiorrhiza Bunge (Danshen), which has been reported as an
anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate
that Sal A inhibits ETAR activation induced by ET-1 in both recombinant and
endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 uM
in the HEK293/ETAR cell line and 3.14 uM in HeLa cells, respectively.
Furthermore, our results showed that Sal A suppressed cell proliferation and
extended the doubling times of multiple cancer cells, including HeLa, DU145,
H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145
cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and
cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells
(HUVEC) and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS
CMs), which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity.
Collectively, our findings indicate that Sal A is a novel anti-cancer candidate
through targeting ETAR.
PMID- 27490541
TI - The Exon Junction Complex Controls the Efficient and Faithful Splicing of a
Subset of Transcripts Involved in Mitotic Cell-Cycle Progression.
AB - The exon junction complex (EJC) that is deposited onto spliced mRNAs upstream of
exon-exon junctions plays important roles in multiple post-splicing gene
expression events, such as mRNA export, surveillance, localization, and
translation. However, a direct role for the human EJC in pre-mRNA splicing has
not been fully understood. Using HeLa cells, we depleted one of the EJC core
components, Y14, and the resulting transcriptome was analyzed by deep sequencing
(RNA-Seq) and confirmed by RT-PCR. We found that Y14 is required for efficient
and faithful splicing of a group of transcripts that is enriched in short intron
containing genes involved in mitotic cell-cycle progression. Tethering of EJC
core components (Y14, eIF4AIII or MAGOH) to a model reporter pre-mRNA harboring a
short intron showed that these core components are prerequisites for the splicing
activation. Taken together, we conclude that the EJC core assembled on pre-mRNA
is critical for efficient and faithful splicing of a specific subset of short
introns in mitotic cell cycle-related genes.
PMID- 27490542
TI - Pharmacological Activities of Ruthenium Complexes Related to Their NO Scavenging
Properties.
AB - Angiogenesis is considered responsible for the growth of primary tumours and of
their metastases. With the present study, the effects of three ruthenium
compounds, potassiumchlorido (ethylendiamminotetraacetate)rutenate(III) (RuEDTA),
sodium (bis-indazole)tetrachloro-ruthenate(III), Na[trans-RuCl4Ind2] (KP1339) and
trans-imidazoledimethylsulphoxidetetrachloro-ruthenate (NAMI-A), are studied in
vitro in models mimicking the angiogenic process. The ruthenium compounds reduced
the production and the release of nitrosyls from either healthy macrophages and
immortalized EA.hy926 endothelial cells. The effects of NAMI-A are qualitatively
similar and sometimes quantitatively superior to those of RuEDTA and KP1339. NAMI
A reduces the production and release of nitric oxide (NO) by the EA.hy926
endothelial cells and correspondingly inhibits their invasive ability; it also
strongly inhibits the angiogenesis in matrigel sponges implanted subcutaneously
in healthy mice. Taken together, these data support the anti-angiogenic activity
of the tested ruthenium compounds and they contribute to explain the selective
activity of NAMI-A against solid tumour metastases, the tumour compartment on
which angiogenesis is strongly involved. This anti-angiogenic effect may also
contribute to the inhibition of the release of metastatic cells from the primary
tumour. Investigations on the anti-angiogenic effects of NAMI-A at this level
will increase knowledge of its pharmacological properties and it will give a
further impulse to the development of this class of innovative metal-based drugs.
PMID- 27490543
TI - Electrochemical Determination of Food Preservative Nitrite with Gold
Nanoparticles/p-Aminothiophenol-Modified Gold Electrode.
AB - Due to the negative impact of nitrate and nitrite on human health, their presence
exceeding acceptable levels is not desired in foodstuffs. Thus, nitrite
determination at low concentrations is a major challenge in electroanalytical
chemistry, which can be achieved by fast, cheap, and safe electrochemical
sensors. In this work, the working electrode (Au) was functionalized with p
aminothiophenol (p-ATP) and modified with gold nanoparticles (Au-NPs) to
manufacture the final (Au/p-ATP-Aunano) electrode in a two-step procedure. In the
first step, p-ATP was electropolymerized on the electrode surface to obtain a
polyaminothiophenol (PATP) coating. In the second step, Au/p-ATP-Aunano working
electrode was prepared by coating the surface with the use of HAuCl4 solution and
cyclic voltammetry. Determination of aqueous nitrite samples was performed with
the proposed electrode (Au/p-ATP-Aunano) using square wave voltammetry (SWV) in
pH 4 buffer medium. Characteristic peak potential of nitrite samples was 0.76 V,
and linear calibration curves of current intensity versus concentration was
linear in the range of 0.5-50 mg.L(-1) nitrite with a limit of detection (LOD) of
0.12 mg.L(-1). Alternatively, nitrite in sausage samples could be
colorimetrically determined with high sensitivity by means of p-ATP-modified gold
nanoparticles (AuNPs) and naphthylethylene diamine as coupling agents for azo-dye
formation due to enhanced charge-transfer interactions with the AuNPs surface.
The slopes of the calibration lines in pure NO2(-) solution and in sausage sample
solution, to which different concentrations of NO2(-) standards were added, were
not significantly different from each other, confirming the robustness and
interference tolerance of the method. The proposed voltammetric sensing method
was validated against the colorimetric nanosensing method in sausage samples.
PMID- 27490545
TI - Preprocessing the Nintendo Wii Board Signal to Derive More Accurate Descriptors
of Statokinesigrams.
AB - During the past few years, the Nintendo Wii Balance Board (WBB) has been used in
postural control research as an affordable but less reliable replacement for
laboratory grade force platforms. However, the WBB suffers some limitations, such
as a lower accuracy and an inconsistent sampling rate. In this study, we focus on
the latter, namely the non uniform acquisition frequency. We show that this
problem, combined with the poor signal to noise ratio of the WBB, can drastically
decrease the quality of the obtained information if not handled properly. We
propose a new resampling method, Sliding Window Average with Relevance Interval
Interpolation (SWARII), specifically designed with the WBB in mind, for which we
provide an open source implementation. We compare it with several existing
methods commonly used in postural control, both on synthetic and experimental
data. The results show that some methods, such as linear and piecewise constant
interpolations should definitely be avoided, particularly when the resulting
signal is differentiated, which is necessary to estimate speed, an important
feature in postural control. Other methods, such as averaging on sliding windows
or SWARII, perform significantly better on synthetic dataset, and produce results
more similar to the laboratory-grade AMTI force plate (AFP) during experiments.
Those methods should be preferred when resampling data collected from a WBB.
PMID- 27490544
TI - Examination of Inertial Sensor-Based Estimation Methods of Lower Limb Joint
Moments and Ground Reaction Force: Results for Squat and Sit-to-Stand Movements
in the Sagittal Plane.
AB - Joint moment estimation by a camera-based motion measurement system and a force
plate has a limitation of measurement environment and is costly. The purpose of
this paper is to evaluate quantitatively inertial sensor-based joint moment
estimation methods with five-link, four-link and three-link rigid body models
using different trunk segmented models. Joint moments, ground reaction forces
(GRF) and center of pressure (CoP) were estimated for squat and sit-to-stand
movements in the sagittal plane measured with six healthy subjects. The five-link
model and the four-link model that the trunk was divided at the highest point of
the iliac crest (four-link-IC model) were appropriate for joint moment estimation
with inertial sensors, which showed average RMS values of about 0.1 Nm/kg for all
lower limb joints and average correlation coefficients of about 0.98 for hip and
knee joints and about 0.80 for ankle joint. Average root mean square (RMS) errors
of horizontal and vertical GRFs and CoP were about 10 N, 15 N and 2 cm,
respectively. Inertial sensor-based method was suggested to be an option for
estimating joint moments of the trunk segments. Inertial sensors were also shown
to be useful for the bottom-up estimation method using measured GRFs, in which
average RMS values and average correlation coefficients were about 0.06 Nm/kg and
larger than about 0.98 for all joints.
PMID- 27490546
TI - Passive Wireless Hermetic Environment Monitoring System for Spray Painting
Workshop.
AB - Passive wireless sensors have the advantages of operating without a power supply
and remote sensing capability. Hence, they are very suitable for some harsh
environments, such as hermetic environments, rotating parts, or very high
temperature environments. The spray painting workshop is such a harsh
environment, containing a large amount of flammable paint mist and organic gas.
Aiming at this special environment of spray painting workshop, a passive wireless
hermetic environment monitoring system was designed, fabricated, and
demonstrated. The proposed system is composed of a transponder and a reader, and
the circuit design of each part is given in detail in this paper. The power and
the data transmission between the transponder and the reader are realized by the
inductive coupling mechanism. Utilizing the back scatter modulation and channel
multiplexing, the frequency signals generated by three different environmental
sensors-together with their interfaces in the transponder-are wirelessly read out
by the reader. Because of the harsh environment of the spray painting room, the
package of the monitoring system is quite important. Three different kinds of
filter films for the system package were compared. The experimental results show
that the composite filter film aluminum anodic oxide/polytetrafluoroethylene
(AAO/PTFE) has the best performance. After fabrication, the measured temperature,
humidity, and pressure sensitivities were measured and found to be 180 Hz/
degrees C in the range of 0~60 degrees C, 100 Hz/%RH in the range of 15~95 %RH,
and 42 Hz/hPa in the range of 600~1100 hPa, respectively. Additionally, the
remote sensing distance of the monitoring system reaches 4 cm. Finally, the
passive wireless hermetic environment monitoring system was installed on the
glass wall of the spray painting workshop and was successfully demonstrated.
PMID- 27490547
TI - Transducer Development and Characterization for Underwater Acoustic Neutrino
Detection Calibration.
AB - A short bipolar pressure pulse with "pancake" directivity is produced and
propagated when an Ultra-High Energy (UHE) neutrino interacts with a nucleus in
water. Nowadays, acoustic sensor networks are being deployed in deep seas to
detect this phenomenon as a first step toward building a neutrino telescope. In
order to study the feasibility of the method, it is critical to have a calibrator
that is able to mimic the neutrino signature. In previous works the possibility
of using the acoustic parametric technique for this aim was proven. In this
study, the array is operated at a high frequency and, by means of the parametric
effect, the emission of the low-frequency acoustic bipolar pulse is generated
mimicking the UHE neutrino acoustic pulse. To this end, the development of the
transducer to be used in the parametric array is described in all its phases. The
transducer design process, the characterization tests for the bare piezoelectric
ceramic, and the addition of backing and matching layers are presented. The
efficiencies and directivity patterns obtained for both primary and parametric
beams confirm that the design of the proposed calibrator meets all the
requirements for the emitter.
PMID- 27490548
TI - Quantitative Determination of Fluorine Content in Blends of Polylactide (PLA)
Talc Using Near Infrared Spectroscopy.
AB - Near-infrared spectroscopy (NIRS) has been widely used for quantitative and/or
qualitative determination of a wide range of matrices. The objective of this
study was to develop a NIRS method for the quantitative determination of fluorine
content in polylactide (PLA)-talc blends. A blending profile was obtained by
mixing different amounts of PLA granules and talc powder. The calibration model
was built correlating wet chemical data (alkali digestion method) and NIR
spectra. Using FT (Fourier Transform)-NIR technique, a Partial Least Squares
(PLS) regression model was set-up, in a concentration interval of 0 ppm of pure
PLA to 800 ppm of pure talc. Fluorine content prediction (R2cal = 0.9498;
standard error of calibration, SEC = 34.77; standard error of cross-validation,
SECV = 46.94) was then externally validated by means of a further 15 independent
samples (R2EX.V = 0.8955; root mean standard error of prediction, RMSEP = 61.08).
A positive relationship between an inorganic component as fluorine and NIR signal
has been evidenced, and used to obtain quantitative analytical information from
the spectra.
PMID- 27490549
TI - Sine Rotation Vector Method for Attitude Estimation of an Underwater Robot.
AB - This paper describes a method for estimating the attitude of an underwater robot.
The method employs a new concept of sine rotation vector and uses both an
attitude heading and reference system (AHRS) and a Doppler velocity log (DVL) for
the purpose of measurement. First, the acceleration and magnetic-field
measurements are transformed into sine rotation vectors and combined. The
combined sine rotation vector is then transformed into the differences between
the Euler angles of the measured attitude and the predicted attitude; the
differences are used to correct the predicted attitude. The method was evaluated
according to field-test data and simulation data and compared to existing methods
that calculate angular differences directly without a preceding sine rotation
vector transformation. The comparison verifies that the proposed method improves
the attitude estimation performance.
PMID- 27490550
TI - Seasonal Mass Changes and Crustal Vertical Deformations Constrained by GPS and
GRACE in Northeastern Tibet.
AB - Surface vertical deformation includes the Earth's elastic response to mass
loading on or near the surface. Continuous Global Positioning System (CGPS)
stations record such deformations to estimate seasonal and secular mass changes.
We used 41 CGPS stations to construct a time series of coordinate changes, which
are decomposed by empirical orthogonal functions (EOFs), in northeastern Tibet.
The first common mode shows clear seasonal changes, indicating seasonal surface
mass re-distribution around northeastern Tibet. The GPS-derived result is then
assessed in terms of the mass changes observed in northeastern Tibet. The GPS
derived common mode vertical change and the stacked Gravity Recovery and Climate
Experiment (GRACE) mass change are consistent, suggesting that the seasonal
surface mass variation is caused by changes in the hydrological, atmospheric and
non-tidal ocean loads. The annual peak-to-peak surface mass changes derived from
GPS and GRACE results show seasonal oscillations in mass loads, and the
corresponding amplitudes are between 3 and 35 mm/year. There is an apparent
gradually increasing gravity between 0.1 and 0.9 MUGal/year in northeast Tibet.
Crustal vertical deformation is determined after eliminating the surface load
effects from GRACE, without considering Glacial Isostatic Adjustment (GIA)
contribution. It reveals crustal uplift around northeastern Tibet from the
corrected GPS vertical velocity. The unusual uplift of the Longmen Shan fault
indicates tectonically sophisticated processes in northeastern Tibet.
PMID- 27490551
TI - INS/GNSS Tightly-Coupled Integration Using Quaternion-Based AUPF for USV.
AB - This paper addresses the problem of integration of Inertial Navigation System
(INS) and Global Navigation Satellite System (GNSS) for the purpose of developing
a low-cost, robust and highly accurate navigation system for unmanned surface
vehicles (USVs). A tightly-coupled integration approach is one of the most
promising architectures to fuse the GNSS data with INS measurements. However, the
resulting system and measurement models turn out to be nonlinear, and the sensor
stochastic measurement errors are non-Gaussian and distributed in a practical
system. Particle filter (PF), one of the most theoretical attractive non
linear/non-Gaussian estimation methods, is becoming more and more attractive in
navigation applications. However, the large computation burden limits its
practical usage. For the purpose of reducing the computational burden without
degrading the system estimation accuracy, a quaternion-based adaptive unscented
particle filter (AUPF), which combines the adaptive unscented Kalman filter
(AUKF) with PF, has been proposed in this paper. The unscented Kalman filter
(UKF) is used in the algorithm to improve the proposal distribution and generate
a posterior estimates, which specify the PF importance density function for
generating particles more intelligently. In addition, the computational
complexity of the filter is reduced with the avoidance of the re-sampling step.
Furthermore, a residual-based covariance matching technique is used to adapt the
measurement error covariance. A trajectory simulator based on a dynamic model of
USV is used to test the proposed algorithm. Results show that quaternion-based
AUPF can significantly improve the overall navigation accuracy and reliability.
PMID- 27490552
TI - Modeling and Analysis of Phase Fluctuation in a High-Precision Roll Angle
Measurement Based on a Heterodyne Interferometer.
AB - Heterodyne interferometry is a high-precision method applied in roll angle
measurements. Phase metering is essential for high precision. During a high
precision measurement, a phase fluctuation appears even when the roll angle does
not vary, which has never been analyzed before. Herein, the reason for the phase
fluctuation is revealed, which results from the frequency-difference fluctuation
and time difference between measurement and reference beams. A mathematical model
of that phase-fluctuation mechanism is established, and that model provides a
theoretical basis for analyzing and reducing the phase fluctuation. The impact
that the main factors have on the phase metering is analyzed quantitatively, and
experiments are carried out to validate the model. Finally, the phase fluctuation
decreases to 0.02 degrees by frequency reduction, which conversely verifies the
theoretical model.
PMID- 27490554
TI - Bindings and RESTlets: A Novel Set of CoAP-Based Application Enablers to Build
IoT Applications.
AB - Sensors and actuators are becoming important components of Internet of Things
(IoT) applications. Today, several approaches exist to facilitate communication
of sensors and actuators in IoT applications. Most communications go through
often proprietary gateways requiring availability of the gateway for each and
every interaction between sensors and actuators. Sometimes, the gateway does some
processing of the sensor data before triggering actuators. Other approaches put
this processing logic further in the cloud. These approaches introduce
significant latencies and increased number of packets. In this paper, we
introduce a CoAP-based mechanism for direct binding of sensors and actuators.
This flexible binding solution is utilized further to build IoT applications
through RESTlets. RESTlets are defined to accept inputs and produce outputs after
performing some processing tasks. Sensors and actuators could be associated with
RESTlets (which can be hosted on any device) through the flexible binding
mechanism we introduced. This approach facilitates decentralized IoT application
development by placing all or part of the processing logic in Low power and Lossy
Networks (LLNs). We run several tests to compare the performance of our solution
with existing solutions and found out that our solution reduces communication
delay and number of packets in the LLN.
PMID- 27490553
TI - Identification of Quorum-Sensing Signal Molecules and a Biosynthetic Gene in
Alicycliphilus sp. Isolated from Activated Sludge.
AB - Activated sludge is a complicated mixture of various microorganisms that is used
to treat sewage and industrial wastewater. Many bacteria produce N-acylhomoserine
lactone (AHL) as a quorum-sensing signal molecule to regulate the expression of
the exoenzymes used for wastewater treatment. Here, we isolated an AHL-producing
bacteria from an activated sludge sample collected from an electronic component
factory, which we named Alicycliphilus sp. B1. Clone library analysis revealed
that Alicycliphilus was a subdominant genus in this sample. When we screened the
activated sludge sample for AHL-producing strains, 12 of 14 the AHL-producing
isolates were assigned to the genus Alicycliphilus. A putative AHL-synthase gene,
ALISP_0667, was cloned from the genome of B1 and transformed into Escherichia
coli DH5alpha. The AHLs were extracted from the culture supernatants of the B1
strain and E. coli DH5alpha cells harboring the ALISP_0667 gene and were
identified by liquid chromatography-mass spectrometry as N-(3-hydroxydecanoyl)-l
homoserine lactone and N-(3-hydroxydodecanoyl)-l-homoserine lactone. The results
of comparative genomic analysis suggested that the quorum-sensing genes in the B1
strain might have been acquired by horizontal gene transfer within activated
sludge.
PMID- 27490555
TI - Topsensterols A-C, Cytotoxic Polyhydroxylated Sterol Derivatives from a Marine
Sponge Topsentia sp.
AB - Three new polyhydroxylated sterol derivatives topsensterols A-C (1-3) have been
isolated from a marine sponge Topsentia sp. collected from the South China Sea.
Their structures were elucidated by detailed analysis of the spectroscopic data,
especially the NOESY spectra. Topsensterols A-C (l-3) possess novel
2beta,3alpha,4beta,6alpha-tetrahydroxy-14alpha-methyl Delta(9(11)) steroidal
nuclei with unusual side chains. Compound 2 exhibited cytotoxicity against human
gastric carcinoma cell line SGC-7901 with an IC50 value of 8.0 MUM. Compound 3
displayed cytotoxicity against human erythroleukemia cell line K562 with an IC50
value of 6.0 MUM.
PMID- 27490556
TI - Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to
Ambient Air Pollutants.
AB - BACKGROUND: It is well established that short-term exposure to ambient air
pollutants can exacerbate asthma, the role of early life or long-term exposure is
less clear. We assessed the association between severe asthma exacerbations with
both birth and annual exposure to outdoor air pollutants with a population-based
cohort of asthmatic children in the province of Quebec (Canada). METHOD:
Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were
defined as one hospitalization or emergency room visit with a diagnosis of asthma
for children (<13 years old) already diagnosed with asthma. Annual daily average
concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the
child's residential postal code. Satellite based levels of fine particulate
(PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes
of residence for the whole province. Hazard ratios (HRs) were estimated from Cox
models with a gap time approach for both birth and time-dependant exposure.
RESULTS: Of the 162,752 asthmatic children followed (1,020,280 person-years),
35,229 had at least one asthma exacerbation. The HRs stratified by age groups and
adjusted for the year of birth, the ordinal number of exacerbations, sex, as well
as material and social deprivation, showed an interquartile range increase in the
time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 MUg/m3)
of 1.095 (95% CI 1.058-1.131), 1.052 (95% CI 1.037-1.066) and 1.025 (95% CI 1.017
1.031), respectively. While a positive association was found to PM2.5, no
associations were found between exposure at birth to NO2 or O3. CONCLUSIONS: Our
results support the conclusion, within the limitation of this study, that asthma
exacerbations in asthmatic children are mainly associated with time dependent
residential exposures less with exposure at birth.
PMID- 27490557
TI - Spatiotemporal Variability of Remotely Sensed PM2.5 Concentrations in China from
1998 to 2014 Based on a Bayesian Hierarchy Model.
AB - With the rapid industrial development and urbanization in China over the past
three decades, PM2.5 pollution has become a severe environmental problem that
threatens public health. Due to its unbalanced development and intrinsic
topography features, the distribution of PM2.5 concentrations over China is
spatially heterogeneous. In this study, we explore the spatiotemporal variations
of PM2.5 pollution in China and four great urban areas from 1998 to 2014. A space
time Bayesian hierarchy model is employed to analyse PM2.5 pollution. The results
show that a stable "3-Clusters" spatial PM2.5 pollution pattern has formed. The
mean and 90% quantile of the PM2.5 concentrations in China have increased
significantly, with annual increases of 0.279 MUg/m3 (95% CI: 0.083-0.475) and
0.735 MUg/m3 (95% CI: 0.261-1.210), respectively. The area with a PM2.5 pollution
level of more than 70 MUg/m3 has increased significantly, with an annual increase
of 0.26 percentage points. Two regions in particular, the North China Plain and
Sichuan Basin, are experiencing the largest amounts of PM2.5 pollution. The
polluted areas, with a high local magnitude of more than 1.0 relative to the
overall PM2.5 concentration, affect an area with a human population of 949
million, which corresponded to 69.3% of the total population in 2010. North and
south differentiation occurs in the urban areas of the Jingjinji and Yangtze
Delta, and circular and radial gradient differentiation occur in the urban areas
of the Cheng-Yu and Pearl Deltas. The spatial heterogeneity of the urban
Jingjinji group is the strongest. Eighteen cities located in the Yangtze Delta
urban group, including Shanghai and Nanjing, have experienced high PM2.5
concentrations and faster local trends of increasing PM2.5. The percentage of
exposure to PM2.5 concentrations greater than 70 MUg/m3 and 100 MUg/m3 is
increasing significantly.
PMID- 27490558
TI - Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with
Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study.
AB - This study investigated the role of CpG island methylation of the CYP2E1 and
CYP2D6 genes in liver injury induced by anti-TB drugs from an epigenetic
perspective in a Chinese cohort. A 1:1 matched nested case-control study design
was applied. Pulmonary tuberculosis (TB) patients, who underwent standard anti-TB
therapy and developed liver injury were defined as cases, while those who did not
develop liver injury were defined as control. The two groups were matched in
terms of sex, treatment regimen, and age. In 114 pairs of cases, CpG island
methylation levels of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were
found to be significantly correlated with the occurrence of anti-TB drug-induced
liver injury (ADLI), with odds ratio (OR) values of 2.429 and 3.500, respectively
(p < 0.01). Moreover, through multivariate logistic regression analysis, CpG
island methylation of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were
found to be significantly correlated with the occurrence of ADLI, with adjusted
OR values of 4.390 (95% confidence interval (CI): 1.982-9.724) and 9.193 (95% CI:
3.624-25.888), respectively (p < 0.001). These results suggest that aberrantly
elevated methylation of CpG islands of the CYP2E1 and CYP2D6 genes in plasma cell
free DNA may increase the risk of ADLI in Chinese TB patients.
PMID- 27490559
TI - Effect of Hypoxia on Ldh-c Expression in Somatic Cells of Plateau Pika.
AB - Sperm specific lactate dehydrogenases (LDH-C4) is a lactate dehydrogenase that
catalyzes the conversion of pyruvate to lactate. In mammals, Ldh-c was originally
thought to be expressed only in testes and spermatozoa. Plateau pika (Ochotona
curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a
hypoxia-tolerant mammal living 3000-5000 m above sea level on the Qinghai-Tibet
Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in
testes and sperm, but also in the somatic tissues of plateau pika. To reveal the
effect of hypoxia on pika Ldh-c expression, we investigated the mRNA and protein
level of Ldh-c as well as the biochemical index of anaerobic glycolysis in pika
somatic tissues at the altitudes of 2200 m, 3200 m and 3900 m. Our results showed
that mRNA and protein expression levels of Ldh-c in the tissues of pika's heart,
liver, brain and skeletal muscle were increased significantly from 2200 m to 3200
m, but had no difference from 3200 m to 3900 m; the activities of LDH and the
contents of lactate showed no difference from 2200 m to 3200 m, but were
increased significantly from 3200 m to 3900 m. Hypoxia up-regulated and
maintained the expression levels of Ldh-c in the pika somatic cells. Under the
hypoxia condition, plateau pikas increased anaerobic glycolysis in somatic cells
by LDH-C4, and that may have reduced their dependence on oxygen and enhanced
their adaptation to the hypoxic environment.
PMID- 27490560
TI - The Impact of Low-Level Lead Toxicity on School Performance among Hispanic
Subgroups in the Chicago Public Schools.
AB - BACKGROUND: Environmental lead exposure detrimentally affects children's
educational performance, even at very low blood lead levels (BLLs). Among
children in Chicago Public Schools (CPS), the severity of the effects of BLL on
reading and math vary by racial subgroup (White vs. Hispanic vs. non-Hispanic
Black). We investigated the impact of BLL on standardized test performance by
Hispanic subgroup (Mexican, Puerto Rican, and Other Hispanic). METHODS: We
examined 12,319 Hispanic children born in Chicago between 1994 and 1998 who were
tested for BLL between birth and 2006 and enrolled in the 3rd grade at a CPS
school between 2003 and 2006. We linked the Chicago birth registry, the Chicago
Blood Lead Registry, and 3rd grade Illinois Standard Achievement Test (ISAT)
scores to examine associations between BLL and school performance. Primary
analyses were restricted to children with BLL below 10 ug/dL (0.483 umol/L).
RESULTS: BLLs below 10 ug/dL (0.483 umol/L) were inversely associated with
reading and math scores in all Hispanic subgroups. Adjusted Relative Risks
(RRadj) and 95% confidence intervals (CI) for reading and math failure were 1.34
(95% CI = 1.25, 1.63) and 1.53 (95% CI = 1.32, 1.78), respectively, per each
additional 5 ug/dL of lead exposure for Hispanic children; RRadj did not differ
across subgroups. We estimate that 7.0% (95% CI = 1.8, 11.9) of reading and 13.6%
(95% CI = 7.7, 19.2) of math failure among Hispanic children can be attributed to
exposure to BLLs of 5-9 ug/dL (0.242 to 0.435 umol/L) vs. 0-4 ug/dL (0-0.193
umol/L). The RRadj of math failure for each 5 ug/dL (0.242 umol/L) increase in
BLL was notably (p = 0.074) stronger among black Puerto Rican children (RRadj =
5.14; 95% CI = 1.65-15.94) compared to white Puerto Rican children (RRadj = 1.50;
95% CI = 1.12-2.02). CONCLUSIONS: Early childhood lead exposure is associated
with poorer achievement on standardized reading and math tests in the 3rd grade
for Mexican, Puerto Rican, and Other Hispanic children enrolled in Chicago Public
Schools. While we did not see interactions between BLL and ISAT performance by
Hispanic subgroup, the stronger association between BLL and math failure for
Black Puerto Rican children is intriguing and warrants further study.
PMID- 27490561
TI - Exposure to Flood Hazards in Miami and Houston: Are Hispanic Immigrants at
Greater Risk than Other Social Groups?
AB - Although numerous studies have been conducted on the vulnerability of
marginalized groups in the environmental justice (EJ) and hazards fields,
analysts have tended to lump people together in broad racial/ethnic categories
without regard for substantial within-group heterogeneity. This paper addresses
that limitation by examining whether Hispanic immigrants are disproportionately
exposed to risks from flood hazards relative to other racial/ethnic groups
(including US-born Hispanics), adjusting for relevant covariates. Survey data
were collected for 1283 adult householders in the Houston and Miami Metropolitan
Statistical Areas (MSAs) and flood risk was estimated using their residential
presence/absence within federally-designated 100-year flood zones. Generalized
estimating equations (GEE) with binary logistic specifications that adjust for
county-level clustering were used to analyze (separately) and compare the Houston
(N = 546) and Miami (N = 560) MSAs in order to clarify determinants of household
exposure to flood risk. GEE results in Houston indicate that Hispanic immigrants
have the greatest likelihood, and non-Hispanic Whites the least likelihood, of
residing in a 100-year flood zone. Miami GEE results contrastingly reveal that
non-Hispanic Whites have a significantly greater likelihood of residing in a
flood zone when compared to Hispanic immigrants. These divergent results suggest
that human-flood hazard relationships have been structured differently between
the two MSAs, possibly due to the contrasting role that water-based amenities
have played in urbanization within the two study areas. Future EJ research and
practice should differentiate between Hispanic subgroups based on nativity status
and attend to contextual factors influencing environmental risk disparities.
PMID- 27490562
TI - Newborn Parent Based Intervention to Increase Child Safety Seat Use.
AB - This paper intends to assess the effect of a maternity department intervention on
improvement of knowledge and use of child safety seats (CSS) among newborn
parents. An intervention study included three groups (one education plus free CSS
intervention group, one education only group, and one control group). The
participants were parents of newborns in the maternity department of two
hospitals. Both of the intervention groups received a folded pamphlet of child
passenger safety, a height chart and standardized safety education during their
hospital stay after giving birth. The education plus free CSS intervention group
received an additional free CSS and professional installation training at
hospital discharge. The control group received a pamphlet with educational
information about nutrition and food safety. Three months after enrollment, a
telephone follow-up was conducted among participants in the three groups. Data on
child passenger safety knowledge, risky driving behaviors, and use of CSS were
evaluated before and after the intervention. A total of 132 newborn parents were
enrolled in the study; of those, 52 (39.4%) were assigned into the education plus
free CSS intervention group, 44 (33.3%) were in the education intervention only
group, and 36 (27.3%) were in the control group. No significant differences
existed in demographics among the three groups. There was a significant
difference in newborn parents' child passenger safety knowledge and behaviors in
the three groups before and after the intervention. In addition, the CSS use
increased significantly in the education plus free CSS group after the
intervention compared to parents in the education only or control groups.
Education on safety, combined with a free CSS and professional installation
training, were effective at increasing newborn parents' knowledge and use of CSS.
Future studies with larger sample sizes and longer follow-up are needed to
determine a long-term effect of the intervention.
PMID- 27490563
TI - High Laccase Expression by Trametes versicolor in a Simulated Textile Effluent
with Different Carbon Sources and PHs.
AB - Textile effluents are highly polluting and have variable and complex
compositions. They can be extremely complex, with high salt concentrations and
alkaline pHs. A fixed-bed bioreactor was used in the present study to simulate a
textile effluent treatment, where the white-rot fungus, Trametes versicolor,
efficiently decolourised the azo dye Reactive Black 5 over 28 days. This occurred
under high alkaline conditions, which is unusual, but advantageous, for
successful decolourisation processes. Active dye decolourisation was maintained
by operation in continuous culture. Colour was eliminated during the course of
operation and maximum laccase (Lcc) activity (80.2 U?L(-1)) was detected after
glycerol addition to the bioreactor. Lcc2 gene expression was evaluated with
different carbon sources and pH values based on reverse transcriptase-PCR
(polymerase chain reaction). Glycerol was shown to promote the highest lcc2
expression at pH 5.5, followed by sucrose and then glucose. The highest levels of
expression occurred between three and four days, which corroborate the maximum
Lcc activity observed for sucrose and glycerol on the bioreactor. These results
give new insights into the use of T. versicolor in textile dye wastewater
treatment with high pHs.
PMID- 27490564
TI - Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability.
AB - Globally eliminating measles using available vaccines is biologically feasible
because the measles virus (MV) hemagglutinin (H) protein is antigenically stable.
The H protein is responsible for receptor binding, and is the main target of
neutralizing antibodies. The immunodominant epitope, known as the
hemagglutinating and noose epitope, is located near the receptor-binding site
(RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding
correlates with an escape from the neutralization by antibodies that target the
epitope at RBS. Another neutralizing epitope is located near RBS and is shielded
by an N-linked sugar in certain genotype strains. However, human sera from
vaccinees and measles patients neutralized all MV strains with similar
efficiencies, regardless of the N-linked sugar modification or mutations at these
epitopes. Two other major epitopes exist at a distance from RBS. One has an
unstructured flexible domain with a linear neutralizing epitope. When MV-H forms
a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface,
and one of the two epitopes may also interact with the F protein. The
neutralization mechanisms of antibodies that recognize these epitopes may involve
inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to
its receptors.
PMID- 27490565
TI - Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with
Similar Potency: Potential Therapeutic Implications.
AB - The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need
for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration
(FDA)-approved drug that blocks EBOV entry and infection in cells and
significantly protects EBOV-challenged mice. As provided, clomiphene is,
approximately, a 60:40 mixture of two stereoisomers, enclomiphene and
zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both
accumulate in the eye and male reproductive tract, tissues in which EBOV can
persist. Here we compared the ability of clomiphene and its isomers to inhibit
EBOV using viral-like particle (VLP) entry and transcription/replication
competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and
infection of VLPs and trVLPs with similar potencies. This was demonstrated with
VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona,
and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems
have been noted in EBOV survivors, and viral RNA has been isolated from semen up
to nine months post-infection. Since the clomiphene isomers accumulate in these
affected tissues, clomiphene or one of its isomers warrants consideration as an
anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV
survivors.
PMID- 27490566
TI - Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited
Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats.
AB - The selectivity and beneficial effects of prebiotics are mainly dependent on
composition and glycosidic linkage among monosaccharide units. This is the first
study to use prebiotic galacto-oligosaccharides (GOS) that contains beta-1,6 and
beta-1,3 glycosidic linkages and the novel combination of GOS and inulin in
cancer prevention. The objective of the present study is to explore the role of
novel GOS and inulin against various biomarkers of colorectal cancer (CRC) and
the incidence of aberrant crypt foci (ACF) in a 1,2-dimethyl hydrazine
dihydrochloride (DMH)-induced rodent model. Prebiotic treatments of combined GOS
and inulin (57 mg each), as well as individual doses (GOS: 76-151 mg; inulin 114
mg), were given to DMH-treated animals for 16 weeks. Our data reveal the
significant preventive effect of the GOS and inulin combination against the
development of CRC. It was observed that inhibition of ACF formation (55.8%) was
significantly (p <= 0.05) higher using the GOS and inulin combination than GOS
(41.4%) and inulin (51.2%) treatments alone. This combination also rendered
better results on short-chain fatty acids (SCFA) and bacterial enzymatic
activities. Dose-dependent effects of prebiotic treatments were also observed on
cecum and fecal bacterial enzymes and on SCFA. Thus, this study demonstrated that
novel combination of GOS and inulin exhibited stronger preventive activity than
their individual treatments alone, and can be a promising strategy for CRC
chemoprevention.
PMID- 27490567
TI - The Effect of Holder Pasteurization on Nutrients and Biologically-Active
Components in Donor Human Milk: A Review.
AB - When a mother's milk is unavailable, the best alternative is donor milk (DM).
Milk delivered to Human Milk Banks should be pasteurized in order to inactivate
the microbial agents that may be present. Currently, pasteurization, performed at
62.5 degrees C for 30 min (Holder Pasteurization, HoP), is recommended for this
purpose in international guidelines. Several studies have been performed to
investigate the effects of HoP on the properties of DM. The present paper has the
aim of reviewing the published papers on this topic, and to provide a comparison
of the reported variations of biologically-active DM components before and after
HoP. This review was performed by searching the MEDLINE, EMBASE, CINHAL and
Cochrane Library databases. Studies that clearly identified the HoP parameters
and compared the same DM samples, before and after pasteurization, were focused
on. A total of 44 articles satisfied the above criteria, and were therefore
selected. The findings from the literature report variable results. A possible
explanation for this may be the heterogeneity of the test protocols that were
applied. Moreover, the present review spans more than five decades, and modern
pasteurizers may be able to modify the degradation kinetics for heat-sensitive
substances, compared to older ones. Overall, the data indicate that HoP affects
several milk components, although it is difficult to quantify the degradation
degree. However, clinical practices demonstrate that many beneficial properties
of DM still persist after HoP.
PMID- 27490568
TI - Selective Membrane Redistribution and Depletion of Galphaq-Protein by Pasteurella
multocida Toxin.
AB - Pasteurella multocida toxin (PMT), the major virulence factor responsible for
zoonotic atrophic rhinitis, is a protein deamidase that activates the alpha
subunit of heterotrimeric G proteins. Initial activation of G alpha-q-coupled
phospholipase C-beta-1 signaling by PMT is followed by uncoupling of G alpha-q
dependent signaling, causing downregulation of downstream calcium and mitogenic
signaling pathways. Here, we show that PMT decreases endogenous and exogenously
expressed G alpha-q protein content in host cell plasma membranes and in
detergent resistant membrane (DRM) fractions. This membrane depletion of G alpha
q protein was dependent upon the catalytic activity of PMT. Results indicate that
PMT-modified G alpha-q redistributes within the host cell membrane from the DRM
fraction into the soluble membrane and cytosolic fractions. In contrast, PMT had
no affect on G alpha-s or G beta protein levels, which are not substrate targets
of PMT. PMT also had no affect on G alpha-11 levels, even though G alpha-11 can
serve as a substrate for deamidation by PMT, suggesting that membrane depletion
of PMT-modified G-alpha-q has specificity.
PMID- 27490569
TI - Putative Nonribosomal Peptide Synthetase and Cytochrome P450 Genes Responsible
for Tentoxin Biosynthesis in Alternaria alternata ZJ33.
AB - Tentoxin, a cyclic tetrapeptide produced by several Alternaria species, inhibits
the F1-ATPase activity of chloroplasts, resulting in chlorosis in sensitive
plants. In this study, we report two clustered genes, encoding a putative non
ribosome peptide synthetase (NRPS) TES and a cytochrome P450 protein TES1, that
are required for tentoxin biosynthesis in Alternaria alternata strain ZJ33, which
was isolated from blighted leaves of Eupatorium adenophorum. Using a pair of
primers designed according to the consensus sequences of the adenylation domain
of NRPSs, two fragments containing putative adenylation domains were amplified
from A. alternata ZJ33, and subsequent PCR analyses demonstrated that these
fragments belonged to the same NRPS coding sequence. With no introns, TES
consists of a single 15,486 base pair open reading frame encoding a predicted
5161 amino acid protein. Meanwhile, the TES1 gene is predicted to contain five
introns and encode a 506 amino acid protein. The TES protein is predicted to be
comprised of four peptide synthase modules with two additional N-methylation
domains, and the number and arrangement of the modules in TES were consistent
with the number and arrangement of the amino acid residues of tentoxin,
respectively. Notably, both TES and TES1 null mutants generated via homologous
recombination failed to produce tentoxin. This study provides the first evidence
concerning the biosynthesis of tentoxin in A. alternata.
PMID- 27490570
TI - Developmental Drift and the Role of Wnt Signaling in Aging.
AB - Population aging is a public health problem affecting the majority of the
developed world. As populations age, the incidence of degenerative diseases
increases exponentially, leading to large increases in public spending on
healthcare. Here we summarize recent findings on the developmental drift theory
of aging, and the links that have been established between aging and the Wnt
signaling pathways. We focus on insights derived from model organisms connecting
the evolutionary basis of aging and the link to developmental programming.
PMID- 27490571
TI - A Hypothesis: Life Initiated from Two Genes, as Deduced from the RNA World
Hypothesis and the Characteristics of Life-Like Systems.
AB - RNA played a central role in the emergence of the first life-like system on
primitive Earth since RNA molecules contain both genetic information and
catalytic activity. However, there are several drawbacks regarding the RNA world
hypothesis. Here, I briefly discuss the feasibility of the RNA world hypothesis
to deduce the RNA functions that are essential for forming a life-like system. At
the same time, I have conducted a conceptual analysis of the characteristics of
biosystems as a useful approach to deduce a realistic life-like system in
relation to the definition of life. For instance, an RNA-based life-like system
should possess enough stability to resist environmental perturbations, by
developing a cell-like compartment, for instance. Here, a conceptual viewpoint is
summarized to provide a realistic life-like system that is compatible with the
primitive Earth environment and the capabilities of RNA molecules. According to
the empirical and conceptual analysis, I propose the hypothesis that the first
life-like system could have initiated from only two genes.
PMID- 27490572
TI - Lariophagus distinguendus (Hymenoptera: Pteromalidae) (Forster)-Past, Present,
and Future: The History of a Biological Control Method Using L. distinguendus
against Different Storage Pests.
AB - Legal requirements and consumer demands for residue-free products pose a big
challenge for pest control in grain stores. One possible alternative to chemical
insecticides is biological pest control with the pteromalid wasp Lariophagus
distinguendus against the weevils Sitophilus granarius, S. oryzae (Coleoptera:
Dryophtoridae), and many other storage pest beetles. The use of this wasp as a
biocontrol agent was already suggested in 1919 by Prof. Dr. Hase [1]. Despite
many studies on host-finding and behavioral biology, the applied aspect was
neglected until 1994. Nowadays the wasps are commercially available and can now
even be reared on-site, facilitating their use tremendously. This review
highlights the milestones in L. distinguendus research, gives insights in current
studies, and ventures a glimpse into the future.
PMID- 27490573
TI - Evaluation of Low versus High Volume per Minute Displacement CO2 Methods of
Euthanasia in the Induction and Duration of Panic-Associated Behavior and
Physiology.
AB - Current recommendations for the use of CO 2 as a euthanasia agent for rats
require the use of gradual fill protocols (such as 10% to 30% volume displacement
per minute) in order to render the animal insensible prior to exposure to levels
of CO 2 that are associated with pain. However, exposing rats to CO 2 ,
concentrations as low as 7% CO 2 are reported to cause distress and 10%-20% CO 2
induces panic-associated behavior and physiology, but loss of consciousness does
not occur until CO 2 concentrations are at least 40%. This suggests that the use
of the currently recommended low flow volume per minute displacement rates create
a situation where rats are exposed to concentrations of CO 2 that induce anxiety,
panic, and distress for prolonged periods of time. This study first characterized
the response of male rats exposed to normoxic 20% CO 2 for a prolonged period of
time as compared to room air controls. It demonstrated that rats exposed to this
experimental condition displayed clinical signs consistent with significantly
increased panic-associated behavior and physiology during CO 2 exposure. When
atmospheric air was then again delivered, there was a robust increase in
respiration rate that coincided with rats moving to the air intake. The rats
exposed to CO 2 also displayed behaviors consistent with increased anxiety in the
behavioral testing that followed the exposure. Next, this study assessed the
behavioral and physiologic responses of rats that were euthanized with 100% CO 2
infused at 10%, 30%, or 100% volume per minute displacement rates. Analysis of
the concentrations of CO 2 and oxygen in the euthanasia chamber and the
behavioral responses of the rats suggest that the use of the very low flow volume
per minute displacement rate (10%) may prolong the duration of panicogenic ranges
of ambient CO 2 , while the use of the higher flow volume per minute displacement
rate (100%) increases agitation. Therefore, of the volume displacement per minute
rates evaluated, this study suggests that 30% minimizes the potential pain and
distress experienced by the animal.
PMID- 27490574
TI - Antioxidant Properties of Water-Soluble Gum from Flaxseed Hulls.
AB - Soluble flaxseed gum (SFG) was extracted from flax (Linum usitatissimum) hulls
using hot water, and its functional groups and antioxidant properties were
investigated using infrared spectroscopy and different antioxidant assays (2,2
diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6
sulphonic acid (ABTS), reducing power capacity, and beta-carotene bleaching
inhibition assay), respectively. The antioxidant capacity of SFG showed
interesting DPPH radical-scavenging capacity (IC50 SFG = 2.5 mg.mL(-1)), strong
ABTS radical scavenging activity (% inhibition ABTS = 75.6% +/- 2.6% at 40 mg.mL(
1)), high reducing power capacity (RPSFG = 5 mg.mL(-1)), and potent beta-carotene
bleaching inhibition activity (IC50 SFG = 10 mg.mL(-1)). All of the obtained
results demonstrate the promising potential use of SFG in numerous industrial
applications, and a way to valorize flaxseed hulls.
PMID- 27490576
TI - Mental Health Difficulties and Help-Seeking Beliefs within a Sample of Female
Partners of UK Veterans Diagnosed with Post-Traumatic Stress Disorder.
AB - In the UK there is a paucity of research about the needs of partners who are
supporting ex-service personnel with mental health difficulties. In this study,
we surveyed the mental health needs and barriers to help-seeking within a sample
of partners of UK veterans who had been diagnosed with PTSD. Our sample included
100 participants. Forty-five percent met criteria for alcohol problems, 39% for
depression, 37% for generalised anxiety disorder and 17% for symptoms of probable
PTSD. Participants who met case criteria for depression, anxiety and problems
with alcohol were more likely to report a greater number of help-seeking
barriers. Participants who were experiencing mental health difficulties were more
likely to endorse barriers connected to stigmatising beliefs than those
associated with practical issues around accessing mental health services. The
evidence presented suggests there may be a considerable burden of mental illness
within this population. It would seem prudent to conduct further work to
understand how best to address this clinical need.
PMID- 27490575
TI - Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of
the T-cell Response by HCV during Chronic Infection.
AB - An effective therapeutic vaccine for the treatment of chronic hepatitis C virus
(HCV) infection, as an adjunct to newly developed directly-acting antivirals
(DAA), or for the prevention of reinfection, would significantly reduce the
global burden of disease associated with chronic HCV infection. A recombinant
chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA),
encoding the non-structural proteins of HCV (NSmut), used in a heterologous
prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific
CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic
than a heterologous Ad regimen. We now assess the immunogenicity of this vaccine
regimen in HCV infected patients (including patients with a low viral load
suppressed with interferon/ribavirin therapy), determine T-cell cross-reactivity
to endogenous virus, and compare immunogenicity with that observed previously in
both healthy volunteers and in HCV infected patients vaccinated with the
heterologous Ad regimen. Vaccination of HCV infected patients with ChAd3
NSmut/MVA-NSmut was well tolerated. Vaccine-induced HCV-specific T-cell responses
were detected in 8/12 patients; however, CD4+ T-cell responses were rarely
detected, and the overall magnitude of HCV-specific T-cell responses was markedly
reduced when compared to vaccinated healthy volunteers. Furthermore, HCV-specific
cells had a distinct partially-functional phenotype (lower expression of
activation markers, granzyme B, and TNFalpha production, weaker in vitro
proliferation, and higher Tim3 expression, with comparable Tbet and Eomes
expression) compared to healthy volunteers. Robust anti-vector T-cells and
antibodies were induced, showing that there is no global defect in immunity. The
level of viremia at the time of vaccination did not correlate with the magnitude
of the vaccine-induced T-cell response. Full-length, next-generation sequencing
of the circulating virus demonstrated that T-cells were only induced by
vaccination when there was a sequence mismatch between the autologous virus and
the vaccine immunogen. However, these T-cells were not cross-reactive with the
endogenous viral variant epitopes. Conversely, when there was complete homology
between the immunogen and circulating virus at a given epitope T-cells were not
induced. T-cell induction following vaccination had no significant impact on HCV
viral load. In vitro T-cell culture experiments identified the presence of T
cells at baseline that could be expanded by vaccination; thus, HCV-specific T
cells may have been expanded from pre-existing low-level memory T-cell
populations that had been exposed to HCV antigens during natural infection,
explaining the partial T-cell dysfunction. In conclusion, vaccination with ChAd3
NSmut and MVA-NSmut prime/boost, a potent vaccine regimen previously optimized in
healthy volunteers was unable to reconstitute HCV-specific T-cell immunity in HCV
infected patients. This highlights the major challenge of overcoming T-cell
exhaustion in the context of persistent antigen exposure.
PMID- 27490577
TI - pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac
Sodium.
AB - Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing
attention in delivery applications due to their capability for controlled drug
release characteristics, biocompatibility, and tunable mechanical, as well as
degradation, properties. However, thorough study is always required while
evaluating potential toxicity of the particles from dose dumping, inconsistent
release and drug-polymer interactions. In this research, we developed PLGA
nanoparticles modified by chitosan (CS), a cationic and pH responsive
polysaccharide that bears repetitive amine groups in its backbone. We used a
model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug
(NSAID), to study the drug loading and release characteristics. PLGA
nanoparticles were synthesized by double-emulsion solvent evaporation technique.
The nanoparticles were evaluated based on their particle size, surface charge,
entrapment efficacy, and effect of pH in drug release profile. About 390-420 nm
of average diameters and uniform morphology of the particles were confirmed by
scanning electron microscope (SEM) imaging and dynamic light scattering (DLS)
measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS.
Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH
responsive drug release in in vitro. The release was about 45% more at pH 5.5
than at pH 7.4. The results of our study indicated the development of chitosan
coating over PLGA nanoparticle for pH dependent controlled release DS drug for
therapeutic applications.
PMID- 27490579
TI - Dissociation and Re-Aggregation of Multicell-Ensheathed Fragments Responsible for
Rapid Production of Massive Clumps of Leptothrix Sheaths.
AB - Species of the Fe/Mn-oxidizing bacteria Leptothrix produce tremendous amounts of
microtubular, Fe/Mn-encrusted sheaths within a few days in outwells of
groundwater that can rapidly clog water systems. To understand this mode of rapid
sheath production and define the timescales involved, behaviors of sheath-forming
Leptothrix sp. strain OUMS1 were examined using time-lapse video at the initial
stage of sheath formation. OUMS1 formed clumps of tangled sheaths. Electron
microscopy confirmed the presence of a thin layer of bacterial exopolymer fibrils
around catenulate cells (corresponding to the immature sheath). In time-lapse
videos, numerous sheath filaments that extended from the periphery of sheath
clumps repeatedly fragmented at the apex of the same fragment, the fragments then
aggregated and again elongated, eventually forming a large sheath clump
comprising tangled sheaths within two days. In this study, we found that fast
microscopic fragmentation, dissociation, re-aggregation and re-elongation events
are the basis of the rapid, massive production of Leptothrix sheaths typically
observed at macroscopic scales.
PMID- 27490578
TI - Electrochemical, Electrochemiluminescence, and Photoelectrochemical Aptamer-Based
Nanostructured Sensors for Biomarker Analysis.
AB - Aptamer-based sensors have been intensively investigated as potential analytical
tools in clinical analysis providing the desired portability, fast response,
sensitivity, and specificity, in addition to lower cost and simplicity versus
conventional methods. The aim of this review, without pretending to be
exhaustive, is to give the readers an overview of recent important achievements
about electrochemical, electrochemiluminescence, and photoelectrochemical
aptasensors for the protein biomarker determination, mainly cancer related
biomarkers, by selected recent publications. Special emphasis is placed on
nanostructured-based aptasensors, which show a substantial improvement of the
analytical performances.
PMID- 27490580
TI - Immunization of Health-Care Providers: Necessity and Public Health Policies.
AB - Health-care providers (HCPs) are at increased risk for exposure to vaccine
preventable diseases (VPDs) in the workplace. The rationale for immunization of
HCPs relies on the need to protect them and, indirectly, their patients from
health-care-associated VPDs. Published evidence indicates significant immunity
gaps for VPDs of HCPs globally. Deficits in knowledge and false perceptions about
VPDs and vaccines are the most common barriers for vaccine uptake and may also
influence communication about vaccines between HCPs and their patients. Most
countries have immunization recommendations for HCPs; however, there are no
universal policies and significant heterogeneity exists between countries in
terms of vaccines, schedules, frame of implementation (recommendation or
mandatory), and target categories of HCPs. Mandatory influenza immunization
policies for HCPs have been implemented with high vaccine uptake rates. Stronger
recommendations for HCP immunization and commitment at the level of the health
care facility are critical in order to achieve high vaccine coverage rates. Given
the importance to health, mandatory immunization policies for VPDs that can cause
serious morbidity and mortality to vulnerable patients should be considered.
PMID- 27490581
TI - Illustrating the Multi-Faceted Dimensions of Group Therapy and Support for Cancer
Patients.
AB - In cancer support groups, choice of therapy model, leadership style, and format
can impact patients' experiences and outcomes. Methodologies that illustrate the
complexity of patients' group experiences might aid in choosing group style, or
testing therapeutic mechanisms. We used this naturalistic study as a beginning
step to explore methods for comparing cancer group contexts by first modifying a
group-experience survey to be cancer-specific (Group Experience Questionnaire
(GEQ)). Hypothesizing that therapist-led (TL) would differ from non-therapist-led
(NTL), we explored the GEQ's multiple dimensions. A total of 292 patients
attending three types of groups completed it: 2 TL groups differing in therapy
style ((1) Supportive-Expressive (SET); (2) The Wellness Community (TWC/CSC));
(3) a NTL group. Participants rated the importance of "Expressing True Feelings"
and "Discussing Sexual Concerns" higher in TL than NTL groups and "Discussing
Sexual Concerns" higher in SET than other groups. They rated "Developing a New
Attitude" higher in TWC/CSC compared to NTL. In addition, we depict the
constellation of group qualities using radar-charts to assist visualization.
These charts facilitate a quick look at a therapy model's strengths and
weaknesses. Using a measure like the GEQ and this visualization technique could
enable health-service decision making about choice of therapy model to offer.
PMID- 27490582
TI - Evaluation of an Education and Training Program to Prevent and Manage Patients'
Violence in a Mental Health Setting: A Pretest-Posttest Intervention Study.
AB - Workplace violence can lead to serious consequences for victims, organizations,
and society. Most workplace violence prevention programs aim to train staff to
better recognize and safely manage at-risk situations. The Omega education and
training program was developed in Canada in 1999, and has since been used to
teach healthcare and mental health workers the skills needed to effectively
intervene in situations of aggression. The present study was designed to assess
the impact of Omega on employee psychological distress, confidence in coping, and
perceived exposure to violence. This program was offered to 105 employees in a
psychiatric hospital in Montreal, Canada. Eighty-nine of them accepted to
participate. Questionnaires were completed before the training, after a short
period of time (M = 109 days) and at follow-up (M = 441 days). Repeated-measures
ANOVAs and Cohen's d effect sizes were calculated. Results demonstrated
statistically significant improvements in short-term and follow-up posttest
scores of psychological distress, confidence in coping, and in levels of exposure
to violence. This study is one of very few to demonstrate the positive impact of
this training program. Further research is needed to understand how to improve
the effectiveness of the program, especially among participants resistant to
change.
PMID- 27490583
TI - Postpartum Bonding Disorder: Factor Structure, Validity, Reliability and a Model
Comparison of the Postnatal Bonding Questionnaire in Japanese Mothers of Infants.
AB - Negative attitudes of mothers towards their infant is conceptualized as
postpartum bonding disorder, which leads to serious health problems in perinatal
health care. However, its measurement still remains to be standardized. Our aim
was to examine and confirm the psychometric properties of the Postnatal Bonding
Questionnaire (PBQ) in Japanese mothers. We distributed a set of questionnaires
to community mothers and studied 392 mothers who returned the questionnaires at 1
month after childbirth. Our model was compared with three other models derived
from previous studies. In a randomly halved sample, an exploratory factor
analysis yielded a three-factor structure: Anger and Restrictedness, Lack of
Affection, and Rejection and Fear. This factor structure was cross-validated by a
confirmatory factor analysis using the other halved sample. The three subscales
showed satisfactory internal consistency. The three PBQ subscale scores were
correlated with depression and psychological abuse scores. Their test-retest
reliability between day 5 and 1 month after childbirth was measured by intraclass
correlation coefficients between 0.76 and 0.83. The Akaike Information Criteria
of our model was better than the original four-factor model of Brockington. The
present study indicates that the PBQ is a reliable and valid measure of bonding
difficulties of Japanese mothers with neonates.
PMID- 27490584
TI - From Biomass-Derived Furans to Aromatics with Ethanol over Zeolite.
AB - We report a novel catalytic conversion of biomass-derived furans and alcohols to
aromatics over zeolite catalysts. Aromatics are formed via Diels-Alder
cycloaddition with ethylene, which is produced in situ from ethanol dehydration.
The use of liquid ethanol instead of gaseous ethylene, as the source of
dienophile in this one-pot synthesis, makes the aromatics production much simpler
and renewable, circumventing the use of ethylene at high pressure. More
importantly, both our experiments and theoretical studies demonstrate that the
use of ethanol instead of ethylene, results in significantly higher rates and
higher selectivity to aromatics, due to lower activation barriers over the solid
acid sites. Synchrotron-diffraction experiments and proton-affinity calculations
clearly suggest that a preferred protonation of ethanol over the furan is a key
step facilitating the Diels-Alder and dehydration reactions in the acid sites of
the zeolite.
PMID- 27490585
TI - Smart Hydrogels with Inhomogeneous Structures Assembled Using Nanoclay-Cross
Linked Hydrogel Subunits as Building Blocks.
AB - A novel and facile assembly strategy has been successfully developed to construct
smart nanocomposite (NC) hydrogels with inhomogeneous structures using nanoclay
cross-linked stimuli-responsive hydrogel subunits as building blocks via
rearranged hydrogen bonding between polymers and clay nanosheets. The assembled
thermoresponsive poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAM-co-AM))
hydrogels with various inhomogeneous structures exhibit excellent mechanical
properties due to plenty of new hydrogen bonding interactions created at the
interface for locking the NC hydrogel subunits, which are strong enough to
tolerate external forces such as high levels of elongations and multicycles of
swelling/deswelling operations. The proposed approach is featured with
flexibility and designability to build assembled hydrogels with diverse
architectures for achieving various responsive deformations, which are highly
promising for stimuli-responsive manipulation such as actuation, encapsulation,
and cargo transportation. Our assembly strategy creates new opportunities for
further developing mechanically strong hydrogel systems with complex
architectures that composed of diverse internal structures, multistimuli
responsive properties, and controllable shape deformation behaviors in the soft
robots and actuators fields.
PMID- 27490586
TI - Introduction.
PMID- 27490587
TI - Pediatric Cardiac Intensive Care: A Transition to Maturity.
PMID- 27490588
TI - Function of the Left and Right Ventricles and the Interactions Between Them.
AB - OBJECTIVES: There has been a recent increase in our understanding of mechanisms
whereby the two sides of the heart interact and modulate each other that may be
particularly relevant to patients in the ICU. For this review, our objectives are
to examine the function of the left ventricle, consider some of the ways in which
the function of the right ventricle differs from that of the left, and examine
the effects of the left ventricle on the function of the right and vice versa.
DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: There are fundamental differences
between the function of the left and right ventricles, which relate to a
significant extent to differences in their respective arterial loads. Although
traditionally it has been usual to consider the function of the left and right
ventricle in isolation, it is now recognized that this approach is flawed and as
a result there is an increasing appreciation of the continual cross talk between
the two sides of the heart in both the normal and diseased states. A more
rational approach to the use of standard therapies frequently used in the cardiac
ICU will come from a better understanding of these important fundamental
concepts, and novel therapeutic concepts are already emerging from new data
regarding biventricular interactions.
PMID- 27490589
TI - Chronic Heart Failure.
AB - OBJECTIVES: The objectives of this review are to discuss the paradigms used to
stage heart failure in children, the classification and physiologic profile of
cardiomyopathies, and the acute and chronic pharmacologic management of heart
failure. DATA SOURCE: MEDLINE, PubMed. CONCLUSION: The etiology of chronic heart
failure in pediatrics is vast. The paradigm of extrapolating adult clinical
trials and technological advancements to treat heart failure in children has
become a nonsustainable model. The field of pediatric heart failure continues to
advance with more robust guideline-directed care and the imminent creation of a
dynamic, contemporary international database. As the field involves a markedly
heterogeneous patient population, it is imperative to use pediatric specific
descriptors of disease impact. The fields of pediatric heart failure and critical
care medicine will continue to evolve together as childhood specific registries,
quality improvement guidelines, and research will lead to practice models
eliciting optimal therapy for patients with heart failure in the intensive care
setting.
PMID- 27490590
TI - Critical Heart Failure and Shock.
AB - OBJECTIVES: The objectives of this review are to discuss the clinical assessment,
pathophysiology, and management of shock, with an emphasis on circulatory
physiology, cardiopulmonary interactions, and pharmacologic strategies to
optimize systemic oxygen delivery. These principles will then be applied to the
clinical syndromes of heart failure and cardiogenic shock that are seen in
children. DATA SOURCE: MEDLINE, PubMed. CONCLUSION: An understanding of essential
circulatory physiology and the pathophysiology of shock are necessary for
managing patients at risk for or in a state of shock. A timely and accurate
assessment of cardiac function, cardiac output, and tissue oxygenation and the
means by which to enhance the relationship between oxygen delivery and
consumption are essential in order to optimize outcomes.
PMID- 27490591
TI - Aortic and Mitral Valve Disease and Left Ventricular Dysfunction in Children.
AB - OBJECTIVES: In this review, we will discuss aortic stenosis, aortic
regurgitation, mitral regurgitation, and mitral stenosis. We will review the
etiology, anatomy, pathophysiology, presentation, and treatment of aortic and
mitral valve disease. Age and lesion specific treatments are outlined based on
the severity of valve disease with an aim at long-term preservation of left
ventricular function. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Mitral and
aortic valve disease leads to unique hemodynamic burdens that can impact left
ventricular function, quality of life, and longevity. The primary challenge in
the management of mitral and aortic valve disease is to apply appropriate medical
management and identify that point in time at which the surgery is necessary.
Although guidelines have been established for the management of aortic and mitral
valve disease in adults, the challenges of early presentation, maintenance of
growth potential, and apparent increased tolerance of hemodynamic burden in
children makes decision making challenging.
PMID- 27490593
TI - Arrhythmias in Cardiac Critical Care.
AB - OBJECTIVES: Here, we characterize the frequency, mechanisms, clinical impact, and
potential treatment options for several arrhythmias commonly encountered in
pediatric cardiac critical care. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS:
Arrhythmias among children in the cardiac critical care setting are common and
clinically important, associated independently with prolonged mechanical
ventilation, critical care unit stay, and an increase in mortality. The precise
characterization of an arrhythmia may provide clues as to an underlying mechanism
as well as serve to guide treatment. Arrhythmia therapy, pharmacologic or
otherwise, is directed toward addressing the underlying mechanism, and as such
may be applicable to the treatment of more than one specific rhythm disturbance.
Decisions concerning therapy must call into consideration an arrhythmia's
underlying etiology, mechanism, and associated hemodynamic embarrassment, along
with the potential for adverse effects of treatment.
PMID- 27490592
TI - Pulmonary Hypertension.
AB - OBJECTIVES: To review the clinical classification, diagnosis, and pathophysiology
of pulmonary hypertension in children, emphasizing the role of right ventricular
function, ventricular interaction, and congenital heart disease in the evolution
and progression of disease, as well as management strategies and therapeutic
options. DATA SOURCE: MEDLINE, PubMed. CONCLUSIONS: Critically ill children with
pulmonary hypertension associated with congenital heart disease are a high-risk
population. Congenital cardiac defects resulting in either increased pulmonary
blood flow or impaired pulmonary venous drainage predispose patients to
developing structural and functional aberrations of the pulmonary vasculature.
Mortality from pulmonary hypertension is most directly related to right
ventricular failure.
PMID- 27490594
TI - Extracorporeal Membrane Oxygenation for Cardiac Indications in Children.
AB - OBJECTIVES: The objectives of this review are to discuss the use of
extracorporeal membrane oxygenation following surgery for congenital heart
disease, myocarditis and as a bridge to cardiac transplantation. In addition, the
latest in circuit equipment, the management of anticoagulation and blood
transfusions, and short- and long-term outcomes are reviewed. DATA SOURCE:
MEDLINE, PubMed. CONCLUSIONS: The use of extracorporeal membrane oxygenation to
support children with heart disease is increasing. There is wide variability in
the use and management of extracorporeal membrane oxygenation between centers.
Many areas of extracorporeal membrane oxygenation management warrant additional
research to inform clinical practice and improve patient outcomes, including the
use of extracorporeal membrane oxygenation in patients undergoing single
ventricle palliation, optimizing strategies for monitoring and titrating
anticoagulation therapies, and efforts directed at minimizing the risk of
neurologic injury.
PMID- 27490595
TI - Ventricular Assist Devices in Pediatric Cardiac Intensive Care.
AB - OBJECTIVES: The objectives of this review are to discuss the process of patient
and mechanical device selection, operative management, and postoperative care
with a focus on the management of right ventricular failure, anticoagulation
strategies, device-related infections and neurologic sequelae. DATA SOURCES:
MEDLINE, PubMed. CONCLUSION: The number of patients with advanced heart failure
due to either acquired or congenital heart disease continues to increase,
necessitating in some mechanical circulatory support and in others cardiac
transplantation. With a limited cardiac donor pool, mechanical circulatory
support is playing a greater role in the management of this population. The
perioperative morbidity associated with mechanical circulatory support has
lessened with improved postoperative management strategies.
PMID- 27490596
TI - Heart Transplantation-The Pediatric Cardiac Critical Care Perspective.
AB - OBJECTIVES: Although there have been tremendous advancements in the care of
severe pediatric cardiovascular disease, heart transplantation remains the
standard therapy for end-stage heart disease in children. As such, these patients
comprise an important and often complex subset of patients in the ICU. The
purpose of this article is to review the causes and management of allograft
dysfunction and the medications used in the transplant population. DATA SOURCES:
MEDLINE, PubMed, and Cochrane Database of systemic reviews. CONCLUSIONS:
Pediatric heart transplant recipients represent a complex group of patients that
frequently require critical care. Their immunosuppressive medications, while
being vital to maintenance of allograft function, are associated with significant
short- and long-term complications. Graft dysfunction can occur from a variety of
etiologies at different times following transplantation and remains a major
limitation to long-term posttransplant survival.
PMID- 27490597
TI - Pulmonary Edema and Hypoxic Respiratory Failure.
AB - OBJECTIVES: The purpose of this chapter is to outline the causes, physiology,
pathophysiology, and management strategies for hydrostatic and permeability
pulmonary edema and hypoxic respiratory failure. DATA SOURCE: MEDLINE and PubMed.
CONCLUSION: The pulmonary parenchyma and vasculature are at high risk in
conditions where injury occurs to the lung and or heart. A targeted approach that
uses strategies that optimize the particular pathophysiology of the parenchyma
and vasculature is required.
PMID- 27490599
TI - Cardiopulmonary Resuscitation in Congenital and Acquired Heart Disease.
AB - OBJECTIVES: The Pediatric Advanced Life Support recommendations were developed
for otherwise healthy infants and children with normal cardiac anatomy. Patients
with acquired and congenital heart disease require specific considerations that
may differ from the Pediatric Advanced Life Support recommendations. Our aim is
to present prearrest, arrest, and postarrest considerations that are unique to
children with congenital and acquired heart disease. DATA SOURCE: MEDLINE and
PubMed. CONCLUSION: A clear understanding of the underlying anatomy and
physiology of congenital and acquired heart disease is imperative in order to
employ the appropriate modifications to the current Pediatric Advanced Life
Support recommendations and to optimize outcomes.
PMID- 27490598
TI - Cardiopulmonary Interactions.
AB - OBJECTIVES: The objectives of this review are to discuss the mechanisms by which
respiration impacts cardiovascular function and vice versa, with an emphasis on
the impact of these interactions in pediatric cardiac critical care. DATA SOURCE:
A search of MEDLINE was conducted using PubMed. CONCLUSIONS: In the presence of
underlying cardiac and respiratory disease, the interplay between these two
systems is significant and plays a pivotal role in the pathophysiology of acute
and chronic phases of a wide spectrum of diseases. An understanding of these
relationships is essential to optimizing the care of critically ill patients.
PMID- 27490600
TI - Near Infrared Spectroscopy as a Hemodynamic Monitor in Critical Illness.
AB - OBJECTIVES: The objectives of this review are to discuss the technology and
clinical interpretation of near infrared spectroscopy oximetry and its clinical
application in patients with congenital heart disease. DATA SOURCE: MEDLINE and
PubMed. CONCLUSION: Near infrared spectroscopy provides a continuous noninvasive
assessment of tissue oxygenation. Over 20 years ago, near infrared spectroscopy
was introduced into clinical practice for monitoring cerebral oxygenation during
cardiopulmonary bypass in adults. Since that time, the utilization of near
infrared spectroscopy has extended into the realm of pediatric cardiac surgery
and is increasingly being used in the cardiac ICU to monitor tissue oxygenation
perioperatively.
PMID- 27490601
TI - Hemodynamic Monitoring.
AB - OBJECTIVES: In this review, we discuss hemodynamic monitoring modalities,
including their application, the interpretation of data, limitations, and impact
on outcomes. DATA SOURCE: MEDLINE, PubMed. CONCLUSIONS: One of the tenets of
critical care medicine is to ensure adequate tissue oxygenation. This assessment
must be timely and accurate to optimize outcomes. The clinical assessment of
cardiac function, cardiac output, and tissue oxygenation based on the physical
examination and standard hemodynamic variables, although an indispensable part of
this exercise, has significant limitations. The use of adjunctive hemodynamic
monitoring modalities provides a much more objective, accurate, and timely
assessment of the patient's hemodynamic profile and is invaluable for assessing
the patient's clinical status, clinical trajectory, and response to
interventions.
PMID- 27490602
TI - Biomarkers in Pediatric Cardiac Critical Care.
AB - OBJECTIVES: In this review, we discuss the physiology, pathophysiology, and
clinical role of troponin, lactate, and B-type natriuretic peptide in the
assessment and management of children with critical cardiac disease. DATA SOURCE:
MEDLINE, PubMed. CONCLUSION: Lactate, troponin, and B-type natriuretic peptide
continue to be valuable biomarkers in the assessment and management of critically
ill children with cardiac disease. However, the use of these markers as a single
measurement is handicapped by the wide variety of clinical scenarios in which
they may be increased. The overall trend may be more useful than any single level
with a persistent or rising value of more importance than an elevated initial
value.
PMID- 27490603
TI - Echocardiography and Focused Cardiac Ultrasound.
AB - OBJECTIVES: The following review will describe the use of focused cardiac
ultrasound performed by noncardiologists and its role as an acute hemodynamic
monitoring tool in pediatric cardiac critical care. DATA SOURCE: MEDLINE and
PubMed. CONCLUSION: The use of focused cardiac ultrasound has grown tremendously
over recent years, and is increasingly being performed and interpreted by
intensivists, anesthesiologists, and emergency medicine physicians. These imaging
techniques are useful in establishing etiologies of cardiac dysfunction and
should compliment the physical examination and standard hemodynamic monitoring.
PMID- 27490604
TI - Sedation and Analgesia in Pediatric Cardiac Critical Care.
AB - OBJECTIVES: This review will focus on the pharmacokinetics (with an emphasis on
the context-sensitive half-time), pharmacodynamics, and hemodynamic
characteristics of the most commonly used sedative/hypnotic, analgesic, and IV
anesthetics used in cardiac intensive care. In addition, the assessment of pain
and agitation and withdrawal will be reviewed. DATA SOURCE: MEDLINE, PubMed.
CONCLUSIONS: Children in the cardiac ICU often require one or more components of
general anesthesia: analgesia, amnesia (sedation and hypnosis), and muscle
relaxation to facilitate mechanical ventilation, to manage postoperative pain, to
perform necessary procedures, and to alleviate fear and anxiety. Furthermore,
these same children are often vulnerable to hemodynamic instability due to unique
underlying physiologic vulnerabilities. An assessment of hemodynamic goals,
postoperative procedures to be performed, physiologic vulnerabilities, and the
intended duration of mechanical ventilation should be made. Based on this
assessment, the optimal selection of sedatives, analgesics, and if necessary,
muscle relaxants can then be made.
PMID- 27490606
TI - Nutrition and Mesenteric Issues in Pediatric Cardiac Critical Care.
AB - OBJECTIVES: The objectives of this review are to discuss the challenges of
delivering adequate nutrition to children with congenital heart disease,
including pre- and postoperative factors and the role of enteral and parenteral
nutrition, as well as the evidence supporting current practices. DATA SOURCE:
MEDLINE and PubMed. CONCLUSION: Providing adequate nutritional support is
paramount for critically ill infants with congenital heart disease, a population
at particular risk for malnutrition. Improved nutritional support has been
associated with increased survival and reduction in overall morbidity. Further
gains can be achieved by creating a clinical culture that emphasizes optimal
perioperative nutritional support. Additional research is required to identify
the specific nutrient composition, optimal mode, and timing of delivery to
maximize clinical benefit.
PMID- 27490607
TI - Acute Kidney Injury and Cardiorenal Syndromes in Pediatric Cardiac Intensive
Care.
AB - OBJECTIVES: The objectives of this review are to discuss the definition,
diagnosis, and pathophysiology of acute kidney injury and its impact on
immediate, short-, and long-term outcomes. In addition, the spectrum of
cardiorenal syndromes will be reviewed including the pathophysiology on this
interaction and its impact on outcomes. DATA SOURCE: MEDLINE and PubMed.
CONCLUSION: The field of cardiac intensive care continues to advance in tandem
with congenital heart surgery. As mortality has become a rare occurrence, the
focus of cardiac intensive care has shifted to that of morbidity reduction. Acute
kidney injury adversely impact outcomes of patients following surgery for
congenital heart disease as well as in those with heart failure (cardiorenal
syndrome). Patients who become fluid overloaded and/or require dialysis are at a
higher risk of mortality, but even minor degrees of acute kidney injury portend a
significant increase in mortality and morbidity. Clinicians continue to seek
methods of early diagnosis and risk stratification of acute kidney injury to
prevent its adverse sequelae.
PMID- 27490605
TI - Neurodevelopmental Outcomes in Children With Congenital Heart Disease-What Can We
Impact?
AB - OBJECTIVES: The objectives of this review are to discuss the scope of neurologic
injuries in newborns with congenital heart disease, the mechanisms of injury,
including prenatal, pre-, intra-, and postoperative factors, neurodevelopmental
outcomes, and therapeutic strategies for the timely intervention and prevention
of neurologic injury. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: At the current
time, important research is underway to 1) better understand the developing brain
in the fetus with complex congenital heart disease, 2) to identify modifiable
risk factors in the operating room and ICU to maximize long-term
neurodevelopmental outcomes, and 3) develop strategies to improve family
psychosocial health, childhood development, and health-related quality of life
following hospital discharge. Crucial in this effort is the identification of an
early postoperative surrogate variable with good predictive validity for long
term outcomes. If an appropriate surrogate variable for long-term outcomes can be
identified, and measured relatively early after surgical intervention for complex
congenital heart disease, reliable clinical trials can be undertaken to improve
upon current outcomes.
PMID- 27490608
TI - Fluid Management: Pharmacologic and Renal Replacement Therapies.
AB - OBJECTIVES: Focusing on critically ill children with cardiac disease, we will
review common causes of fluid perturbations, clinical recognition, and strategies
to minimize and treat fluid-related complications. DATA SOURCE: MEDLINE and
PubMed. CONCLUSIONS: Meticulous fluid management is vital in critically ill
children with cardiac disease. Fluid therapy is important to maintain adequate
blood volume and perfusion pressure in order to support cardiac output, tissue
perfusion, and oxygen delivery. However, fluid overload and acute kidney injury
are common and are associated with increased morbidity and mortality.
Understanding the etiologies for disturbances in volume status and the
pathophysiology surrounding those conditions is crucial for providing optimal
care.
PMID- 27490610
TI - Cardiopulmonary Bypass-Induced Inflammatory Response: Pathophysiology and
Treatment.
AB - OBJECTIVES: The objectives of this review are to discuss the pathophysiology of
the pro-inflammatory response to the cardiopulmonary bypass circuit, the impact
of ischemia reperfusion injury on post-operative organ function, the compensatory
anti-inflammatory response and the evidence for immune-modulatory strategies and
their impact on outcomes. DATA SOURCE: MEDLINE, PubMed. CONCLUSION: Innovations
such as the development of more biocompatible surfaces and miniaturized circuits,
as well as the increasing expertise of surgeons, anesthesiologists and
perfusionists has transformed cardiac surgery and the use of cardiopulmonary
bypass into a relatively routine procedure with favorable outcomes. Despite these
refinements, the attendant inflammatory response to bypass, ischemia reperfusion
injury and the compensatory anti-inflammatory response contribute to post
operative morbidity and mortality. Additional studies are needed to further
delineate the impact of immunomodulatory strategies on outcomes.
PMID- 27490611
TI - Avoidance of Hospital-Acquired Infections in Pediatric Cardiac Surgical Patients.
AB - OBJECTIVES: The objectives of this review are to discuss the prevalence and risk
factors associated with the development of hospital-acquired infections in
pediatric patients undergoing cardiac surgery and the published antimicrobial
prophylaxis regimens and rational approaches to the diagnosis, prevention, and
treatment of nosocomial infections in these patients. DATA SOURCE: MEDLINE and
PubMed. CONCLUSION: Hospital-acquired infections remain a significant source of
potentially preventable morbidity and mortality in pediatric cardiac surgical
patients. Through improved understanding of these conditions and implementation
of avoidance strategies, centers caring for these patients may improve outcomes
in this vulnerable population.
PMID- 27490609
TI - Sepsis in Pediatric Cardiac Intensive Care.
AB - OBJECTIVES: In this review, we will discuss risk factors for developing sepsis;
the role of biomarkers in establishing an early diagnosis, in monitoring
therapeutic efficacy, in stratification, and for the identification of sepsis
endotypes; and the pathophysiology and management of severe sepsis and septic
shock, with an emphasis on the impact of sepsis on cardiovascular function. DATA
SOURCE: MEDLINE and PubMed. CONCLUSIONS: There is a lot of excitement in the
field of sepsis research today. Scientific advances in the diagnosis and clinical
staging of sepsis, as well as a personalized approach to the treatment of sepsis,
offer tremendous promise for the future. However, at the same time, it is also
evident that sepsis mortality has not improved enough, even with progress in our
understanding of the molecular pathophysiology of sepsis.
PMID- 27490612
TI - Bleeding and Thrombosis in Pediatric Cardiac Intensive Care.
AB - OBJECTIVES: The objective of this article is to review the particular tendencies
as well as specific concerns of bleeding and clotting in children with critical
cardiac disease. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: Children with
critical heart disease are at particular risk for bleeding and clotting secondary
to intrinsic as well as extrinsic factors. We hope that this review will aid the
clinician in managing the unique challenges of bleeding and clotting in this
patient population, and serve as a springboard for much needed research in this
area.
PMID- 27490613
TI - Endocrinologic Diseases in Pediatric Cardiac Intensive Care.
AB - OBJECTIVES: The objectives of this review are to discuss the pathophysiology,
clinical impact and treatment of hyperglycemia, and disturbances in thyroid and
adrenal function prior to and following cardiac surgery in children. DATA SOURCE:
MEDLINE and PubMed. CONCLUSIONS: Disturbances in glucose metabolism and thyroid
and adrenal function are common in critically ill children with cardiac disease
and in particular in children undergoing cardiac surgery for complex congenital
heart disease. An understanding of the pathophysiology, clinical impact and
treatment of these disturbances is essential for the management of these at risk
patients.
PMID- 27490614
TI - Shunt Lesions Part I: Patent Ductus Arteriosus, Atrial Septal Defect, Ventricular
Septal Defect, and Atrioventricular Septal Defect.
AB - OBJECTIVES: This review summarizes the current understanding of the
pathophysiology and perioperative management of patent ductus arteriosus, atrial
septal defect, ventricular septal defect, and atrioventricular septal defect.
DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: The four congenital cardiac lesions
that are the subject of this review, patent ductus arteriosus, atrial septal
defect, ventricular septal defect, and atrioventricular septal defect, are the
most commonly found defects causing a left-to-right shunt. These defects
frequently warrant transcatheter or surgical intervention. Although the
perioperative care is relatively straightforward for many of these patients,
there are a number of management strategies and complications associated with
each intervention. The treatment outcomes for all of these lesions are very good
in the current era.
PMID- 27490615
TI - Shunt Lesions Part II: Anomalous Pulmonary Venous Connections and Truncus
Arteriosus.
AB - OBJECTIVES: The objectives of this review are to describe the anatomy,
pathophysiology, perioperative therapeutic strategies, and operative procedures
for patients with anomalous pulmonary venous connections and truncus arteriosus.
DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: An understanding of the anatomy and
pathophysiology of anomalous pulmonary venous connections and truncus arteriosus
is essential for the optimal perioperative management of these complex and
challenging congenital lesions.
PMID- 27490616
TI - Left Ventricular Outflow Tract Obstruction: Coarctation of the Aorta, Interrupted
Aortic Arch, and Borderline Left Ventricle.
AB - OBJECTIVES: The objectives of this review are to discuss the perioperative
management of coarctation of the aorta, interrupted aortic arch, and the
borderline left ventricle. METHODS: MEDLINE and PubMed. CONCLUSIONS: Successful
management of systemic obstructive lesions involves a thorough evaluation of the
anatomy and pathophysiology to determine the most effective management strategy.
PMID- 27490617
TI - Hypoplastic Left Heart Syndrome and Other Shunt-Dependent Single Ventricles.
AB - OBJECTIVES: In this review, we discuss the pathophysiology, treatment, and
outcomes of patients with the hypoplastic left heart syndrome and other single
ventricle variants prior to and following surgery. DATA SOURCE: MEDLINE and
PubMed. CONCLUSIONS: Patients with shunted single ventricle physiology are at
increased risk for acute hemodynamic decompensation owing to the increased
myocardial workload, the dynamic balance between systemic and pulmonary
circulations, and the potential for shunt obstruction. Understanding of the
physiology and anticipatory management are critical to prevent hemodynamic
compromise and cardiac arrest.
PMID- 27490618
TI - Right Ventricular Outflow Tract Obstruction: Pulmonary Atresia With Intact
Ventricular Septum, Pulmonary Stenosis, and Ebstein's Malformation.
AB - OBJECTIVES: The objectives of this review are to discuss the anatomy,
pathophysiology, clinical course, and current treatment strategies for pulmonary
atresia with intact ventricular septum, pulmonary stenosis, and Ebstein's
anomaly. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Considerable advances have
been made in management strategies for these complex congenital heart lesions,
which have led to improved outcomes.
PMID- 27490619
TI - Tetralogy of Fallot and Its Variants.
AB - OBJECTIVES: The objectives of this review are to discuss the anatomy,
pathophysiology, surgical repair, and perioperative management strategies for
tetralogy of Fallot and its variants. DATA SOURCE: MEDLINE and PubMed.
CONCLUSIONS: Significant refinements have been made in the repair strategy for
tetralogy of Fallot, based on improved understanding of postrepair physiology.
Important considerations for timing and technique of surgery and perioperative
management have been presented, and continued evolution is expected. Expanded use
of the pulmonary valve reconstruction technique outlined herein, whatever the age
of repair, may improve long-term outcome.
PMID- 27490620
TI - Transposition of the Great Arteries and Common Variants.
AB - OBJECTIVES: The objectives of this review are to discuss the physiology,
perioperative management, surgical correction, and outcomes of infants with
transposition of the great arteries and common variants undergoing the arterial
switch operation. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: The widespread
adoption of the arterial switch operation for transposition of great arteries has
been one of the more gratifying advances in pediatric cardiovascular care, and
represents the simultaneous improvements in diagnostics, surgical and bypass
techniques, anesthesia in the neonate, improvements in intensive care technology,
nursing strategies, and system-wide care delivery. Many of the strategies adopted
for the neonate with transposition of the great arteries have been translated to
neonatal care for other congenital heart lesions. Continued work is necessary to
investigate the effects of perioperative care on long-term neurodevelopmental
outcomes, as well as collaboration between centers to spread "best practices" for
outcome, cost, and morbidity reduction.
PMID- 27490621
TI - L-Transposition of the Great Arteries.
AB - OBJECTIVES: To describe the various surgical options, perioperative management
strategies, and outcomes for this complex lesion. DATA SOURCE: MEDLINE and
PubMed. CONCLUSIONS: L-transposition of the great arteries is a relatively rare
defect, comprising less than 1% of all congenital heart defects. There is
considerable heterogeneity in clinical presentation depending on the presence of
associated defects. Surgery for this rare and complex defect has evolved from
"physiologic" repair in which the right ventricle remains in the systemic
position to the "anatomic" repair, which restores the left ventricle as the
systemic ventricle. There has been a great interest in performing the anatomic
repair or "double switch" operation, a rather complex operation that presents
unique challenges in the postoperative period.
PMID- 27490622
TI - Clinical-Physiological Considerations in Patients Undergoing Staged Palliation
for a Functionally Single Ventricle.
AB - OBJECTIVES: The objectives of this review are to discuss the pathophysiology of
the circulation with a functionally univentricular heart, with a focus on the
unique physiologic characteristics, which provide the underpinnings for the
management of these complex patients. DATA SOURCE: MEDLINE and PubMed.
CONCLUSIONS: The circulation of the patient with a functionally univentricular
heart displays unique physiologic characteristics, which are quite different from
those of the normal biventricular circulation. There are profound differences
within the heart itself in terms of ventricular function, interventricular
interactions, and myocardial architecture, which are likely to have significant
implications for the efficiency of ventricular ejection and metabolism. The
coupling between the systemic ventricle and the aorta also displays unique
features. The 3D orientation of the Fontan anastomosis itself can profoundly
impact cardiac output, although the "portal" pulmonary arterial bed is a crucial
determinant of overall cardiovascular function. As a result, disease-specific
approaches to improve cardiovascular function are required at all stages during
the care of these complex patients.
PMID- 27490623
TI - Acquired and Congenital Coronary Artery Diseases.
AB - OBJECTIVES: The objectives of this review are to discuss the spectrum of coronary
artery anomalies and the evidence behind current treatment strategies. DATA
SOURCE: MEDLINE and PubMed. CONCLUSION: Coronary artery anomalies exist in up to
1% of the population and most of these do not cause symptoms or ischemia and do
not require any surgical intervention whereas others are potentially fatal. The
type of surgical intervention is often dictated by the type of lesion, and upon
the unique anatomic and physiologic variables associated with each lesion.
Postoperative care can be challenging particularly after surgical repair of
anomalous left coronary artery from the pulmonary artery.
PMID- 27490624
TI - Outcomes Analysis and Quality Improvement in Children With Congenital and
Acquired Cardiovascular Disease.
AB - OBJECTIVES: In this review, the current state of outcomes analysis and quality
improvement in children with acquired and congenital cardiovascular disease will
be discussed, with an emphasis on defining and measuring outcomes and quality in
pediatric cardiac critical care medicine and risk stratification systems. DATA
SOURCE: MEDLINE and PubMed CONCLUSION: : Measuring quality and outcomes in the
pediatric cardiac critical care environment is challenging owing to many inherent
obstacles, including a diverse patient mix, difficulty in determining how the
care of the ICU team contributes to outcomes, and the lack of an adequate risk
adjustment method for pediatric cardiac critical care patients. Despite these
barriers, new solutions are emerging that capitalize on lessons learned from
other quality improvement initiatives, providing opportunities to build upon
previous successes.
PMID- 27490625
TI - Comorbid Conditions in Neonates With Congenital Heart Disease.
AB - OBJECTIVES: The objectives of this review are to discuss the pathophysiology,
clinical impact and treatment of major noncardiac anomalies, and prematurity in
infants with congenital heart disease. DATA SOURCE: MEDLINE and PubMed.
CONCLUSION: Mortality risk is significantly higher in patients with congenital
heart disease and associated anomalies compared with those in whom the heart
defect occurs in isolation. Although most noncardiac structural anomalies do not
require surgery in the neonatal period, several require surgery for survival.
Management of such infants poses multiple challenges. Premature infants with
congenital heart disease face challenges imposed by their immature organ systems,
which are susceptible to injury or altered function by congenital heart disease
and abnormal circulatory physiology independent of congenital heart disease. For
optimal outcomes in premature infants or in infants with multiple congenital
anomalies, a collaborative interdisciplinary approach is necessary.
PMID- 27490626
TI - Intensive Care in the Adult With Congenital Heart Disease.
AB - OBJECTIVES: The purpose of this review is to discuss current outcomes for
patients with adult congenital heart disease, assess the level of knowledge
regarding the impact of comorbidities, and discuss the various models of care
with a view to establish the optimal environment for the care of these patients
in the future. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: There is an
increasingly large population of adults with previously operated congenital heart
disease. Consequently, there are increasing numbers of adults requiring intensive
care support after re-do surgery, or as a consequence of medical complications of
their underlying cardiac disease. There is relatively little data specific to
this population to guide optimal disposition and care models.
PMID- 27490627
TI - Nursing Considerations in Pediatric Cardiac Critical Care.
AB - OBJECTIVE: The objectives of this review are to describe the education and
critical thinking skills that characterize pediatric critical care nursing and
how these skills impact patient care and outcomes in pediatric cardiac critical
care. DATA SOURCE: MEDLINE and PubMed. CONCLUSIONS: Pediatric cardiac critical
care nurses manage complex and vulnerable patients requiring various levels of
support. Effective care of these patients requires knowledge about the complex
anatomy and physiology associated with congenital and acquired heart disease, as
well as the effects of mechanical ventilation, mechanical circulatory support,
and vasoactive medications. Strong physical examination skills, accurate
interpretation of hemodynamic and laboratory data, active participation in
bedside rounds, excellent communication skills, meticulous care of invasive
monitoring catheters and tubes, and compassionate support of families are among
the skills that distinguish a cardiac critical care nurse.
PMID- 27490628
TI - Global Perspectives On Pediatric Cardiac Critical Care.
AB - OBJECTIVES: The objectives of this review are to discuss the global epidemiology
of cardiovascular disease, emphasizing congenital heart disease; to discuss the
concept of epidemiologic transition and its role in studying the evolving
epidemiology of disease; and to assess and address the global burden of
congenital heart disease including its prevention and treatment. DATA SOURCE:
MEDLINE and PubMed. CONCLUSIONS: Despite impressive reductions in mortality from
congenital and acquired cardiovascular disease in high-income countries, these
reductions have not been observed on a global scale. It will be necessary to
continue our attempts to extend rational programs of care to middle- and low
income countries based on community empowerment, economics, and population
health. The specialist in pediatric cardiac critical care can be a central driver
of these programs.
PMID- 27490629
TI - The cosmopolitan contradictions of planetary urbanization.
AB - This paper explores the empirical, conceptual and theoretical gains that can be
made using cosmopolitan social theory to think through the urban transformations
that scholars have in recent years termed planetary urbanization. Recognizing the
global spread of urbanization makes the need for a cosmopolitan urban sociology
more pressing than ever. Here, it is suggested that critical urban sociology can
be invigorated by focusing upon the disconnect that Henri Lefebvre posits between
the planetarization of the urban - which he views as economically and
technologically driven - and his dis-alienated notion of a global urban society.
The first aim of this paper is to highlight the benefits of using 'cosmopolitan'
social theory to understand Lefebvre's urban problematic (and to establish why
this is also a cosmopolitan problematic); the second is to identify the core
cosmopolitan contradictions of planetary urbanization, tensions that are both
actually existing and reproduced in scholarly accounts. The article begins by
examining the challenges presented to urban sociology by planetary urbanization,
before considering how cosmopolitan sociological theory helps provide an
analytical 'grip' on the deep lying social realities of contemporary
urbanization, especially in relation to questions about difference, culture and
history. These insights are used to identify three cosmopolitan contradictions
that exist within urbanized (and urbanizing) space; tensions that provide a basis
for a thoroughgoing cosmopolitan investigation of planetary urbanization.
PMID- 27490630
TI - Genome editing comes of age.
AB - Genome editing harnesses programmable nucleases to cut and paste genetic
information in a targeted manner in living cells and organisms. Here, I review
the development of programmable nucleases, including zinc finger nucleases
(ZFNs), TAL (transcription-activator-like) effector nucleases (TALENs) and CRISPR
(cluster of regularly interspaced palindromic repeats)-Cas9 (CRISPR-associated
protein 9) RNA-guided endonucleases (RGENs). I specifically highlight the key
advances that set the foundation for the rapid and widespread implementation of
CRISPR-Cas9 genome editing approaches that has revolutionized the field.
PMID- 27490631
TI - Looking to the future following 10 years of induced pluripotent stem cell
technologies.
AB - The development of induced pluripotent stem cells (iPSCs) has fundamentally
changed our view on developmental cell-fate determination and led to a cascade of
technological innovations in regenerative medicine. Here we provide an overview
of the progress in the field over the past decade, as well as our perspective on
future directions and clinical implications of iPSC technology.
PMID- 27490632
TI - Cell-type-specific profiling of protein-DNA interactions without cell isolation
using targeted DamID with next-generation sequencing.
AB - This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007);
doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile
transcription and chromatin binding in a cell-type-specific manner is a powerful
aid to understanding cell-fate specification and cellular function in
multicellular organisms. We recently developed targeted DamID (TaDa) to enable
genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins
in vivo without cell isolation. As a protocol extension, this article describes
substantial modifications to an existing protocol, and it offers additional
applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA
binding profiles of proteins, by coupling it with the GAL4 system in Drosophila
to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion
proteins are expressed at very low levels, thus avoiding toxicity and potential
artifacts from overexpression. The modifications to the core DamID technique
presented here also increase the speed of sample processing and throughput, and
adapt the method to next-generation sequencing technology. TaDa is robust,
reproducible and highly sensitive. Compared with other methods for cell-type
specific profiling, the technique requires no cell-sorting, cross-linking or
antisera, and binding profiles can be generated from as few as 10,000 total
induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol
II), TaDa can also identify transcribed genes in a cell-type-specific manner.
Here we describe a detailed protocol for carrying out TaDa experiments and
preparing the material for next-generation sequencing. Although we developed TaDa
in Drosophila, it should be easily adapted to other organisms with an inducible
expression system. Once transgenic animals are obtained, the entire experimental
procedure-from collecting tissue samples to generating sequencing libraries-can
be accomplished within 5 d.
PMID- 27490634
TI - Reply to "Reducing Gender Discrepancies in Academic Radiology".
PMID- 27490633
TI - High-quality full-length immunoglobulin profiling with unique molecular
barcoding.
AB - High-throughput sequencing analysis of hypermutating immunoglobulin (IG)
repertoires remains a challenging task. Here we present a robust protocol for the
full-length profiling of human and mouse IG repertoires. This protocol uses
unique molecular identifiers (UMIs) introduced in the course of cDNA synthesis to
control bottlenecks and to eliminate PCR and sequencing errors. Using asymmetric
400+100-nt paired-end Illumina sequencing and UMI-based assembly with the new
version of the MIGEC software, the protocol allows up to 750-nt lengths to be
sequenced in an almost error-free manner. This sequencing approach should also be
applicable to various tasks beyond immune repertoire studies. In IG profiling,
the achieved length of high-quality sequence covers the variable region of even
the longest chains, along with the fragment of a constant region carrying
information on the antibody isotype. The whole protocol, including preparation of
cells and libraries, sequencing and data analysis, takes 5 to 6 d.
PMID- 27490635
TI - Does asymptomatic recurrent diffuse capillary C4d complement deposition impair
cardiac allograft function?
AB - BACKGROUND: The aim of this study was to evaluate whether asymptomatic recurrent
(>=2) antibody-mediated rejection (pAMR 1+), defined as diffuse capillary C4d
immunostaining (rAMR) on endomyocardial biopsies (EMBs), during the first year
after heart transplantation impairs left ventricular (LV) function. METHODS:
Fifty-four consecutive heart transplant patients who survived well (New York
Heart Association <=2 and EF>=55%) the first month after transplantation were
enrolled and prospectively underwent 490 echocardiographies and EMB. Asymptomatic
rAMR without histopathologic findings was evaluated as a risk factor for
deterioration of graft function. Primary endpoint, assessed 1 year after
transplantation, was development of LV dysfunction and/or adverse remodeling
according to pre-specified echo parameters. RESULTS: During the first year from
transplantation, rAMR occurred in five patients. Recurrent AMR was associated
with a significant higher risk to develop LV concentric hypertrophy (OR 3.6, 95%
CI: 1.8-7.0, P=.02) or reduced lateral S' peak velocity (OR 2.3, 95% CI: 1.5-3.6,
P=.03). Patients with rAMR showed significative adverse graft remodeling (DeltaLV
end-diastolic volume: +16+/-12.3 vs -0.2+/-14.4 mL; P=.02) and deterioration of
graft function (Deltalateral S' peak velocity: -3.3+/-3 vs -0.4+/-2.9 cm/s;
P=.03). CONCLUSIONS: Recurrent asymptomatic diffuse capillary C4d immunostaining
may play a role in the early development of cardiac allograft adverse remodeling
and dysfunction.
PMID- 27490636
TI - EUCheMS Lecture Award: G. Ferey and C. Moberg / August Wilhelm von Hofmann
Memorial Medal: B. L. Feringa / Catalan-Sabatier Prize: J.-M. Tarascon / Elhuyar
Goldschmidt Lectureship: N. Martin and F. Wurthner / European Federation for
Medicinal Chemistry Awards: F. Diederich and P. J. Hergenrother / Eni Awards: J.
A. Lercher and D. Milstein.
PMID- 27490637
TI - Advancing HIV research with pregnant women: navigating challenges and
opportunities.
AB - OBJECTIVE: Concerns about including pregnant women in research have led to a
dearth of evidence to guide safe and effective treatment and prevention of HIV in
pregnancy. To better understand why these evidence gaps persist and inform
guidance for responsible inclusion of pregnant women in the HIV research agenda,
we aimed to learn what HIV experts perceive as barriers and constraints to
conducting this research. METHODS: We conducted a series of group and one-on-one
consultations with 62 HIV investigators and clinicians to elicit their views and
experiences conducting HIV research involving pregnant women. Thematic analysis
was used to identify priorities and perceived barriers to HIV research with
pregnant women. RESULTS: Experts discussed a breadth of needed research,
including safety, efficacy, and appropriate dosing of: newer antiretrovirals for
pregnant women, emerging preventive strategies, and treatment for coinfections.
Challenges to conducting research on pregnancy and HIV included ethical concerns,
such as how to weigh risks and benefits in pregnancy; legal concerns, such as
restrictive interpretations of current regulations and liability issues;
financial and professional disincentives, including misaligned funder priorities
and fear of reputational damage; and analytical and logistical complexities, such
as challenges recruiting and retaining pregnant women to sufficiently power
analyses. CONCLUSION: Investigators face numerous challenges to conducting needed
HIV research with pregnant women. Advancing such research will require clearer
guidance regarding ethical and legal uncertainties; incentives that encourage
rather than discourage investigators to undertake such research; and a commitment
to earlier development of safety and efficacy data through creative trial
designs.
PMID- 27490639
TI - Associations between antiretroviral use and subclinical coronary atherosclerosis.
AB - OBJECTIVES: HIV infection is associated with increased prevalence of subclinical
coronary plaque. The extent to which such plaque reflects effects of HIV
infection or effects of long-term antiretroviral therapy (ART) use remains
unclear and was the goal of this analysis. DESIGN AND METHODS: We compared the
prevalence and extent of coronary plaque and stenosis between users of specific
ART drugs or drug classes using coronary computed tomography (CT) among HIV
infected men in the Multicenter AIDS Cohort Study. To account for time-dependent
confounders, including cardiovascular disease risk factors and time-varying
reasons for using specific treatments, we conducted fully adjusted logistic and
linear models with inverse probability of treatment weighting. RESULTS: There
were 618 men who underwent noncontrast coronary CT; 450 also underwent coronary
CT angiography. At the time of scanning, 81% had undetectable plasma HIV RNA. In
fully adjusted models, cumulative use of zidovudine, abacavir, darunavir, and
protease inhibitors as a drug class were inconsistently associated with specific
forms of plaque presence or extent. CONCLUSION: Among virally suppressed HIV
infected men with extensive ART exposure, no consistent associations between use
of specific ART drugs and both subclinical coronary plaque presence and extent
were apparent. Our findings support the hypothesis that, among virally suppressed
persons, type of ART used is not in general a major determinant of subclinical
coronary plaque risk.
PMID- 27490638
TI - Prevalence and predictors of low muscle mass in HIV/viral hepatitis coinfection.
AB - OBJECTIVE: Low muscle mass is associated with reduced survival in HIV, possibly
mediated by systemic inflammation. Viral hepatitis coinfection can induce
additional inflammation and hepatic dysfunction that may exacerbate low muscle
mass. We determined the prevalence of and risk factors for low muscle mass in
HIV/viral hepatitis coinfection. DESIGN AND METHODS: A cross-sectional study of
participants in the Multicenter AIDS Cohort Study and Women's Interagency HIV
Study with anthropometry performed after 1 January 2000. Viral hepatitis defined
by positive hepatitis B virus surface antigen and/or hepatitis C virus RNA. Low
muscle mass defined as less than 10th percentile of age-matched and sex-matched
reference values for mid-upper arm circumference. Using multivariable logistic
regression, we determined adjusted odds ratios with 95% confidence intervals
(CIs) of the association of HIV/viral hepatitis coinfection with low muscle mass
and factors associated with low muscle mass in coinfected persons. Analyses
adjusted for age, race, BMI, alcohol use, and IDU (also, nadir CD4 cell count and
HIV RNA where appropriate). RESULTS: Among 3518 participants (164 HIV/viral
hepatitis, 223 viral hepatitis alone, 1070 HIV alone, and 2061 uninfected),
HIV/viral hepatitis-coinfected persons had a 3.50-fold (95% CI, 1.51-8.09), 1.93
fold (1.17-3.20), and 2.65-fold (1.62-4.35) higher odds of low muscle mass than
viral hepatitis-monoinfected, HIV-monoinfected, and uninfected persons,
respectively. Lack of HIV RNA suppression [odds ratio, 2.26 (95% CI, 1.10-4.63)]
was the only factor associated with low muscle mass in coinfected persons.
CONCLUSION: HIV/viral hepatitis-coinfected persons have a higher likelihood of
low muscle mass than those with viral hepatitis monoinfection, HIV monoinfection,
or neither infection. HIV viremia is an important risk factor for low muscle mass
among coinfected persons.
PMID- 27490641
TI - Acute HIV infection transmission among people who inject drugs in a mature
epidemic setting.
AB - OBJECTIVE: Estimates for the contribution of transmission arising from acute HIV
infections (AHIs) to overall HIV incidence vary significantly. Furthermore,
little is known about AHI-attributable transmission among people who inject drugs
(PWID), including the extent to which interventions targeting chronic infections
(e.g. HAART as prevention) are limited by AHI transmission. Thus, we estimated
the proportion of transmission events attributable to AHI within the mature HIV
epidemic among PWID in New York City (NYC). DESIGN: Modeling study. METHODS: We
constructed an interactive sexual and injecting transmission network using an
agent-based model simulating the HIV epidemic in NYC between 1996 and 2012. Using
stochastic microsimulations, we cataloged transmission from PWID based on the
disease stage of index agents to determine the proportion of infections
transmitted during AHI (in primary analyses, assumed to last 3 months). RESULTS:
Our calibrated model approximated the epidemiological features of the mature HIV
epidemic in NYC between 1996 and 2012. Annual HIV incidence among PWID dropped
from approximately 1.8% in 1996 to 0.7% in 2012. Over the 16-year period, AHI
accounted for 4.9% (10th/90th percentile: 0.1-12.3%) of incident HIV cases among
PWID. The annualized contribution of AHI increased over this period from 3.6% in
1996 to 5.9% in 2012. CONCLUSION: Our results suggest that, in mature epidemics
such as NYC, between 3% and 6% of transmission events are attributable to AHI
among PWID. Current HIV treatment as prevention strategies are unlikely to be
substantially affected by AHI-attributable transmission among PWID populations in
mature epidemic settings.
PMID- 27490644
TI - Double trouble: a rare case of bilateral intratonsillar abscess.
PMID- 27490643
TI - Neonatal Acute Kidney Injury and the Risk of Intraventricular Hemorrhage in the
Very Low Birth Weight Infant.
AB - Despite improvements in survival of premature infants, many have comorbid
conditions. The role of the kidney in multiorgan dysfunction is unclear,
particularly in regard to intraventricular hemorrhage (IVH). We hypothesized that
infants diagnosed with acute kidney injury (AKI) have an increased risk of IVH
independent of gestational age (GA) and other variables associated with both
comorbidities. This prospective cohort study consisted of 125 infants with a
birth weight <=1,200 g and/or GA <=31 weeks. A definition of AKI was used from
KDIGO, not including urine output as nonoliguria is common in this population.
IVH was based on serial head ultrasounds. Neonates with AKI had a higher trend
towards having IVH compared to those without [14/35 (40%) vs. 22/83 (26.5%), p =
0.1]. Infants with AKI were more likely to have stage 2 IVH or higher than those
without AKI [12/36 (33.3%) vs. 6/82 (7.3%); p < 0.01]. AKI was associated with a
3.6-fold increased risk of a grade 2 or higher IVH [hazard ratio (HR) 3.55, 95%
confidence interval (CI) 1.39-9.07] and over 4-fold increase in risk of a grade 3
or higher IVH (HR 4.34, 95% CI 1.43-13.21). While there was no association
between AKI and IVH overall, those with AKI had a higher hazard ratio to develop
a grade 2 or higher IVH even when controlling for birth weight, antenatal steroid
use, and 5-min Apgar score. Future studies are indicated to expand sample size
and to control for other clinical variables that could be associated with both
AKI and IVH.
PMID- 27490642
TI - Programed death-1/programed death-ligand 1 expression in lymph nodes of HIV
infected patients: results of a pilot safety study in rhesus macaques using anti
programed death-ligand 1 (Avelumab).
AB - OBJECTIVE: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway
plays a critical role in balancing immunity and host immunopathology. During
chronic HIV/SIV infection, there is persistent immune activation accompanied by
accumulation of virus-specific cells with terminally differentiated phenotypes
and expression of regulatory receptors such as PD1. These observations led us to
hypothesize that the PD1/PD-L1 pathway contributes to the functional
dysregulation and ineffective viral control, and its blockade may be a potential
immunotherapeutic target. METHODS: Lymph node biopsies from HIV-infected patients
(n = 23) were studied for expression of PD1 and PD-L1. In addition, we assessed
the safety and biological activity of a human anti-PD-L1 antibody (Avelumab) in
chronically SIV-infected rhesus macaques. RESULTS: PD-L1 expression was observed
in cells with myloid/macrophage morphology in HIV-infected lymph nodes.
Administration of anti-PD-L1 was well tolerated, and no changes in body weights,
hematologic, or chemistry parameters were observed during the study. Blockade of
PD-L1 led to a trend of transient viral control after discontinuation of
treatment. CONCLUSION: Administration of anti-PD-L1 in chronic SIV-infected
rhesus macaques was well tolerated. Overall, these data warrant further
investigation to assess the efficacy of anti-PD-L1 treatment on viral control in
chronic SIV infection as a prelude to such therapy in humans.
PMID- 27490646
TI - pH-Responsive Relaxometric Behaviour of Coordination Polymer Nanoparticles Made
of a Stable Macrocyclic Gadolinium Chelate.
AB - Lanthanide-containing nanoscale particles have been widely explored for various
biomedical purposes, however, they are often prone to metal leaching. Here we
have created a new coordination polymer (CP) by applying, for the first time, a
stable Gd(III) chelate as building block in order to prevent any fortuitous
release of free lanthanide(III) ion. The use of the Gd-DOTA-4AmP complex as a
design element in the CP allows not only for enhanced relaxometric properties
(maximum r1 =16.4 mm(-1) s(-1) at 10 MHz), but also for a pH responsiveness
(Deltar1 =108 % between pH 4 and 6.5), beyond the values obtained for the low
molecular weight Gd-DOTA-4AmP itself. The CP can be miniaturised to the nanoscale
to form colloids that are stable in physiological saline solution and in cell
culture media and does not show cytotoxicity.
PMID- 27490645
TI - Single nucleotide polymorphisms in an intergenic chromosome 2q region associated
with tissue factor pathway inhibitor plasma levels and venous thromboembolism.
AB - Essentials Tissue factor pathway inhibitor (TFPI) regulates the blood coagulation
cascade. We replicated previously reported linkage of TFPI plasma levels to the
chromosome 2q region. The putative causal locus, rs62187992, was associated with
TFPI plasma levels and thrombosis. rs62187992 was marginally associated with TFPI
expression in human aortic endothelial cells. Click to hear Ann Gil's
presentation on new insights into thrombin activatable fibrinolysis inhibitor
SUMMARY: Background Tissue factor pathway inhibitor (TFPI) regulates fibrin clot
formation, and low TFPI plasma levels increase the risk of arterial
thromboembolism and venous thromboembolism (VTE). TFPI plasma levels are also
heritable, and a previous linkage scan implicated the chromosome 2q region, but
no specific genes. Objectives To replicate the finding of the linkage region in
an independent sample, and to identify the causal locus. Methods We first
performed a linkage analysis of microsatellite markers and TFPI plasma levels in
251 individuals from the F5L Family Study, and replicated the finding of the
linkage peak on chromosome 2q (LOD = 3.06). We next defined a follow-up region
that included 112 603 single nucleotide polymorphisms (SNPs) under the linkage
peak, and meta-analyzed associations between these SNPs and TFPI plasma levels
across the F5L Family Study and the Marseille Thrombosis Association (MARTHA)
Study, a study of 1033 unrelated VTE patients. SNPs with false discovery rate q
values of < 0.10 were tested for association with TFPI plasma levels in 892
patients with coronary artery disease in the AtheroGene Study. Results and
Conclusions One SNP, rs62187992, was associated with TFPI plasma levels in all
three samples (beta = + 0.14 and P = 4.23 * 10-6 combined; beta = + 0.16 and P =
0.02 in the F5L Family Study; beta = + 0.13 and P = 6.3 * 10-4 in the MARTHA
Study; beta = + 0.17 and P = 0.03 in the AtheroGene Study), and contributed to
the linkage peak in the F5L Family Study. rs62187992 was also associated with
clinical VTE (odds ratio 0.90, P = 0.03) in the INVENT Consortium of > 7000 cases
and their controls, and was marginally associated with TFPI expression (beta = +
0.19, P = 0.08) in human aortic endothelial cells, a primary site of TFPI
synthesis. The biological mechanisms underlying these associations remain to be
elucidated.
PMID- 27490647
TI - Experience with Lumbar Puncture Following Endoscopic Third Ventriculostomy for
Obstructive Hydrocephalus.
AB - Background and Objective The increase in intracranial pressure (ICP) in some
patients in the immediate postoperative period following endoscopic third
ventriculostomy (ETV) is not well understood. This study explored the effect of
lumbar puncture following ETV for obstructive hydrocephalus on outcome. Materials
and Methods A total of 145 patients with obstructive hydrocephalus underwent ETV
between 2009 and 2014. Following ETV, all patients underwent lumbar puncture on
postoperative days 1 and 3. Results In 106 patients, ICP returned to normal
levels accompanied by symptom relief. In 39 patients, ICP remained high on
postoperative days 3, and lumbar puncture was continued every alternate
postoperative day for 11 days. ICP always returned to normal. These 39 patients
were divided into two groups for analysis: group A (age < 18 years) and group B
(age >= 18 years). Peak values of ICP for groups A and B were recorded on days 3
and 5, respectively. Conclusions Our study suggests an important role for
postoperative lumbar puncture in ensuring successful treatment results after ETV.
In most of the symptomatic patients with obstructive hydrocephalus, lumbar
puncture appears to contribute to rapid ICP normalization, to alleviation of
symptoms, and prevention of complications.
PMID- 27490648
TI - Special Series on Mental Health.
PMID- 27490649
TI - One-Visit Behavioral Intervention for Older Primary Care Patients with Mild to
Moderate Depressive Symptoms.
AB - OBJECTIVES: We pilot tested a one-visit behavioral intervention with telephone
follow-up for older primary care patients with mild to moderate depressive
symptoms. METHODS: A total of 16 English-speaking primary care patients aged 60
years and older who scored 5 to 14 on the Patient Health Questionnaire-9 (PHQ-9)
engaged in the intervention visit. Outcomes were assessed at baseline and 4
weeks: activity goals, readiness to change (University of Rhode Island Change
Assessment), PHQ-9, Generalized Anxiety Disorder-7, World Health Organization
Disability Assessment Schedule 2.0, and satisfaction. RESULTS: The 14
participants who completed the study met or exceeded 73% of activity goals on
average. They also improved on all outcomes (P < 0.05) with medium (University of
Rhode Island Change Assessment, GAD-7) to large effect sizes (PHQ-9, World Health
Organization Disability Assessment Schedule 2.0), and they were satisfied.
CONCLUSIONS: This pilot study provided preliminary evidence that a one-visit
behavioral activation intervention is acceptable and feasible and improves
outcomes. If findings are confirmed, then this intervention could be integrated
into existing collaborative care programs.
PMID- 27490650
TI - Commentary on "One-Visit Behavioral Intervention for Older Primary Care Patients
with Mild to Moderate Depressive Symptoms".
PMID- 27490651
TI - Conversion Disorder in an Appalachian Community.
AB - OBJECTIVES: Conversion disorder (CD) is believed to be the manifestation of
physical and/or neurological symptoms for primary gain without an identifiable
organic cause. Although it is believed to be more common in rural areas, the
literature examining this claim is sparse. To our knowledge, no study has been
published evaluating the prevalence of CD in a rural Appalachian population. The
aim of this study was to characterize and determine the prevalence of CD per
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria in a
rural Appalachian psychiatric consultation service and to compare this population
with control patients from the same service. METHODS: We performed a
retrospective chart review of all patients diagnosed as having CD per Diagnostic
and Statistical Manual of Mental Disorders, 5th Edition, criteria on a
psychiatric consultation service at a rural Appalachian academic medical center
during a 13-month time period. For each case, two consecutive control patients
were selected from the same service and time span. RESULTS: There were 21 cases
and 42 controls in this study, with a CD prevalence rate of 6.0% (N = 21/351).
Sociodemographic, comorbidity, and recent symptomatology data were obtained.
Compared with controls, cases were significantly younger and were more likely to
have a history of sexual abuse, seizure disorder, antiepileptic use, neurologic
referral, electroencephalogram, magnetic resonance imaging of the brain, and
history of CD. We found it interesting that fewer cases reported alcohol and drug
use. CONCLUSIONS: The observed prevalence of 6.0% does not support the historical
theory that CD is more prevalent in rural or lower socioeconomic populations. Our
data add to the characterization of the Appalachian CD population.
PMID- 27490652
TI - Impact of Nutrition on Neurocognition.
PMID- 27490653
TI - Commentary on "Impact of Nutrition on Neurocognition".
PMID- 27490655
TI - Homelessness and Emergency Psychiatric Evaluations.
PMID- 27490654
TI - Mental Health Impact of Hosting Disaster Refugees: Analyses from a Random Sample
Survey Among Haitians Living in Miami.
AB - OBJECTIVES: Studies on the mental health of families hosting disaster refugees
are lacking. This study compares participants in households that hosted 2010
Haitian earthquake disaster refugees with their nonhost counterparts. METHODS: A
random sample survey was conducted from October 2011 through December 2012 in
Miami-Dade County, Florida. Haitian participants were assessed regarding their
2010 earthquake exposure and impact on family and friends and whether they hosted
earthquake refugees. Using standardized scores and thresholds, they were
evaluated for symptoms of three common mental disorders (CMDs): posttraumatic
stress disorder, generalized anxiety disorder, and major depressive disorder
(MDD). RESULTS: Participants who hosted refugees (n = 51) had significantly
higher percentages of scores beyond thresholds for MDD than those who did not
host refugees (n = 365) and for at least one CMD, after adjusting for
participants' earthquake exposures and effects on family and friends.
CONCLUSIONS: Hosting refugees from a natural disaster appears to elevate the risk
for MDD and possibly other CMDs, independent of risks posed by exposure to the
disaster itself. Families hosting refugees deserve special attention.
PMID- 27490656
TI - Does Timing of Internal Medicine Residency Interview Affect Likelihood of
Matching?
AB - OBJECTIVES: Applicants to our internal medicine (IM) residency program
consistently have shared concerns about whether the interview date influences
their ability to match via the National Residency Matching Program. We performed
a retrospective study to assess whether interview timing was associated with
successful matching at our IM program. METHODS: We identified all of the
applicants who interviewed for a first-year position with our IM residency
program from 2010 to 2014. Each year's interview dates were totaled and divided
equally into three categories: early, middle, or late. Baseline demographics,
United States Medical Licensing Examination scores, and type of medical school
(American or international) were compared among the interview date groups and
between those who did and did not match at our program. RESULTS: Of 914
interviewees, 311 interviewed early (October/November), 299 interviewed in the
middle (December), and 304 interviewed late (January). The proportion to match at
our program was similar in each interview group (12.5%, 18.4%, 15.1%,
respectively; P = 0.133). Logistic regression analysis showed that the middle
interview group had increased odds to match compared with the early group (odds
ratio 1.590; P = 0.044). The late-versus-early group showed no difference (P =
0.362). No significant differences were found with type of medical school or
United States Medical Licensing Examination scores. Of all of the interviewees
participating in the match, nearly all matched into a program somewhere, with no
significant difference based on interview timing. CONCLUSIONS: When considering
all of the interviewees, interview date showed no major influence on matching.
Only the middle interview time period showed a slight increased chance of
matching to our IM program, but the significance was marginal.
PMID- 27490657
TI - Fostering Clinical Excellence Across an Academic Health System.
AB - OBJECTIVES: Changes in the US healthcare economic system are requiring academic
health centers (AHCs) to restructure in pursuit of their traditional tripartite
missions; engaging the individuals focused on clinical care is becoming more
important. We conducted this study to guide our institution's transformation by
identifying ways to formally recognize clinicians who are excelling in patient
care and understand which forms of acknowledgment would be acceptable and
motivating. METHODS: A survey was developed by a large committee with
representation spanning the AHC and was sent electronically in spring 2014 to
stakeholders across the institution. Items assessed perceptions of the importance
and present state of valuing clinical excellence, the utility of 14 potential
metrics to assess clinical excellence, and the meaningfulness of seven potential
rewards for clinical excellence. Bivariate and multivariate logistic regression
models analyzed differences (P < 0.05) by respondent sex, ethnicity, academic
rank, primary clinical affiliation, and time spent in patient care and research
activities. RESULTS: A total of 1716 of 3168 (54%) stakeholders responded,
including 1198 of 2151 (56%) individuals from academic hospitals, 114 of 276
(41%) from the outpatient affiliated practices, and 304 of 741 (54%) from
satellite locations. Nearly everyone (96%) agreed that clinical accomplishments
should be recognized, although a minority (47%) believed that clinicians were
already valued. Most respondents selected 7 or more of 14 metrics as valid and
reasonable for assessing clinical excellence. Popular metrics (eg, clinical
productivity) were not believed to represent clinical excellence as much as
others (eg, professionalism). Multivariate analysis found the least agreement
among stakeholders on using published scholarship as evidence for clinical
excellence, with the widest differences comparing senior faculty versus
nonfaculty (88% vs 27%) and those with >75% of their time spent in patient care
versus others (37% vs 73%). Most (six of seven) types of reward were perceived as
meaningful by the majority of respondents, with little variation among subgroups
across bivariate and multivariate analyses. CONCLUSIONS: This system-wide
assessment was successful at identifying new strategies for recognizing clinical
excellence. Other AHCs seeking institutional transformation may wish to perform a
similar assessment.
PMID- 27490658
TI - Patient Perceptions of Oseltamivir for the Treatment of Influenza.
AB - OBJECTIVES: Oseltamivir (Tamiflu) is approved by the Food and Drug Administration
and is advertised for the treatment of influenza types A and B. Patient
perceptions of its efficacy have not been adequately studied. Recent systematic
reviews have called the benefits of this drug into question relative to the cost
and adverse effect profile. We hypothesized that most people would be unaware of
the efficacy, cost, or adverse effect profile of the drug. Our objective was to
determine patient perceptions of efficacy, cost, and adverse effect profile of
oseltamivir for the treatment of influenza. METHODS: This was a cross-sectional,
multiple-choice, open-response survey of adult patients and adult caregivers of
pediatric patients who presented to the emergency department (ED) with flu-like
symptoms. Flu-like symptoms were defined as any respiratory symptom plus fever or
body aches. The study took place during the 2014-2015 flu season at a rural ED.
We analyzed the data, with descriptive statistics reported as
frequencies/percentages for categorical data. Survey data collected as Likert
scale data were summarized using mean, median, and mode. RESULTS: During the 4
month period, 70 surveys were completed. A total of 67% of the participants were
women, with 84% younger than 40 years. Subjects younger than 40 years were more
likely to have seen advertising for oseltamivir (31% vs 0%, P = 0.04). Less than
half reported having received the flu vaccine that year. Most reported that
oseltamivir was an effective treatment for the flu. Most overstated the perceived
efficacy of oseltamivir. Most were not willing to take the medication if it had
adverse effects, with the most deterring adverse effects being potential kidney
and liver injury. CONCLUSIONS: In our study most patients reported overly
positive expectations for the efficacy of oseltamivir for treating influenza.
Most reported that commonly listed adverse effects would deter their use of the
medication.
PMID- 27490659
TI - Clinical Features of Respiratory Viral Infections Among Inpatients at a Major US
Tertiary Care Hospital.
AB - OBJECTIVES: Respiratory viral illnesses (RVI) are reliably diagnosed by
respiratory viral panel using polymerase chain reaction (RVP-PCR); however, owing
to the scant data, clinical presentation alone is unreliable in establishing
viral etiology. The primary objective of this study was to characterize signs and
symptoms of RVI among inpatients in a major tertiary care hospital. METHODS:
Between 2013 and 2015, adult inpatients with RVI undergoing RVP-PCR were
prospectively enrolled in our study. Clinical data were collected by interviews
and electronic medical record reviews. Data analysis was performed using chi(2)
testing, analysis of variance for continuous variables, and logistic regression
modeling. RESULTS: Of 421 patients analyzed, 175 (41.7%) had a positive RVP-PCR.
Patients were evenly matched at baseline except for renal disease. Multivariate
logistic regression modeling demonstrated the following positive correlations:
positive RVP-PCR with renal disease (odds ratio [OR] 2.08), cough (OR 2.28), and
wheezing (OR 1.8); influenza with cough (OR 5.04), and renal disease (OR 2.17);
metapneumovirus with age older than 65 (OR 3.24); respiratory syncytial viruses
with wheezing (OR 3.42) and immunosuppression (OR 3.11); and parainfluenza with
smoking (OR 3.16). Negative correlations included influenza with anosmia (OR
0.41); rhinovirus/enterovirus with feeling confined to bed (OR 0.3);
metapneumovirus with smoking (OR 0.29); and parainfluenza with male sex (OR
0.22). CONCLUSIONS: In this descriptive study, we noted specific viral
associations with clinical signs and symptoms among 421 inpatients with RVIs.
With increasing RVP-PCR use, studies similar to ours may be able to better define
the clinical presentation of RVIs and lead to evidence-based, clinical
presentation-guided diagnostic and management algorithms.
PMID- 27490660
TI - Determinants of Elevated Alkaline Phosphatase in Patients Infected with HIV.
AB - OBJECTIVES: A retrospective cross-sectional study was performed to assess the
prevalence of elevated alkaline phosphatase (ALP) in patients infected with human
immunodeficiency virus (HIV) and to determine the relation between ALP and
specific antiretroviral therapy (ART). METHODS: A total of 2990 patients were
included in this study. Data were collected from a major academic institution's
HIV clinic using the most recent searchable values from patients' medical
records. Included patients were 18 to 89 years old, had HIV, and their ALP
results were available. Elevated ALP was defined as ALP >120 IU/L. Logistic
regression analyses were performed to calculate odds ratios (ORs) and 95%
confidence intervals (CIs) for predictors of elevated ALP level. RESULTS: In our
total population of 2990, 15.4% (n = 459) had elevated ALP. In the bivariate
analyses, older age (>=60 years; OR 4.1, 95% CI 2.6-6.4), female sex (OR 1.6, 95%
CI 1.3-1.9), Other race (not African American) vs white (OR 1.9, 95% CI 1.8-3.3),
elevated creatinine (OR 2.9, 95% CI 2.1-4.1), laboratory evidence of liver
disease (OR 2.1, 95% CI 1.7-2.6), CD4 count <200 cells per cubic millimeter (OR
2.5, 95% CI 2.0-3.2), hepatitis C infection (OR 1.9, 95% CI 1.4-2.5), laboratory
markers of bone turnover (OR 1.9, 95% CI 1.2-3.1), and non-nucleoside reverse
transcriptase inhibitors use (OR 1.2, 95% CI 1.02-1.15) were significantly
associated with elevated ALP. Only the association with laboratory markers of
bone turnover remained significant in the multivariate analysis, however.
CONCLUSIONS: The results suggest that comorbidities and demographic variables
have stronger associations with elevated ALP than specific antiretroviral
therapy. Future research should be conducted to define the clinical significance
of elevated ALP among patients infected with HIV.
PMID- 27490661
TI - How Is Zika Transmitted?
PMID- 27490662
TI - Life-Long Radar Tracking of Bumblebees.
AB - Insect pollinators such as bumblebees play a vital role in many ecosystems, so it
is important to understand their foraging movements on a landscape scale. We used
harmonic radar to record the natural foraging behaviour of Bombus terrestris
audax workers over their entire foraging career. Every flight ever made outside
the nest by four foragers was recorded. Our data reveal where the bees flew and
how their behaviour changed with experience, at an unprecedented level of detail.
We identified how each bee's flights fit into two categories-which we named
exploration and exploitation flights-examining the differences between the two
types of flight and how their occurrence changed over the course of the bees'
foraging careers. Exploitation of learned resources takes place during efficient,
straight trips, usually to a single foraging location, and is seldom combined
with exploration of other areas. Exploration of the landscape typically occurs in
the first few flights made by each bee, but our data show that further
exploration flights can be made throughout the bee's foraging career. Bees showed
striking levels of variation in how they explored their environment, their
fidelity to particular patches, ratio of exploration to exploitation, duration
and frequency of their foraging bouts. One bee developed a straight route to a
forage patch within four flights and followed this route exclusively for six days
before abandoning it entirely for a closer location; this second location had not
been visited since her first exploratory flight nine days prior. Another bee made
only rare exploitation flights and continued to explore widely throughout its
life; two other bees showed more frequent switches between exploration and
exploitation. Our data shed light on the way bumblebees balance exploration of
the environment with exploitation of resources and reveal extreme levels of
variation between individuals.
PMID- 27490664
TI - Social reasoning abilities in preterm and full-term children aged 5-7years.
AB - BACKGROUND: Literature has evidenced behavioral and socio-emotional problems in
preterm children, as well as long-term difficulties to establish and maintain
social relationships in preterm population. Several studies have shown relations
between behavior and social reasoning abilities in typically developing children
and adults. AIM: The present study aimed to investigate the social understanding
and social reasoning abilities in preterm children aged between 5 and 7years in
comparison to their full-term peers. STUDY DESIGN: A social resolution task (SRT)
was used to assess abilities to judge, identify and reason about others' behavior
in relation to conventional and moral rules knowledge. SUBJECTS: 102 preterm
children and 88 full-term children were included in the study. RESULTS: Compared
with their full-term peers, preterm children exhibited difficulties to understand
and reason about inappropriate social behavior, particularly for situations
related to the transgression of conventional rules. They used more irrelevant
information and exhibited less social awareness when reasoning about the
transgression of social rules. The only significant predictor for global SRT and
social reasoning scores was the mental processing composite of the K-ABC, but the
part of the variance of the SRT that could be explained by the general cognitive
abilities was relatively small. CONCLUSION: Preterm children demonstrated poorer
social knowledge and social reasoning abilities compared with full-term children
at early school age. Improving such abilities may reduce behavioral difficulties
and peer relationship problems often described in the preterm population. These
findings emphasize the need to early identify children at risk for impaired
social development.
PMID- 27490663
TI - Lipid Body Organelles within the Parasite Trypanosoma cruzi: A Role for
Intracellular Arachidonic Acid Metabolism.
AB - Most eukaryotic cells contain varying amounts of cytosolic lipidic inclusions
termed lipid bodies (LBs) or lipid droplets (LDs). In mammalian cells, such as
macrophages, these lipid-rich organelles are formed in response to host-pathogen
interaction during infectious diseases and are sites for biosynthesis of
arachidonic acid (AA)-derived inflammatory mediators (eicosanoids). Less clear
are the functions of LBs in pathogenic lower eukaryotes. In this study, we
demonstrated that LBs, visualized by light microscopy with different probes and
transmission electron microscopy (TEM), are produced in trypomastigote forms of
the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, after both
host interaction and exogenous AA stimulation. Quantitative TEM revealed that LBs
from amastigotes, the intracellular forms of the parasite, growing in vivo have
increased size and electron-density compared to LBs from amastigotes living in
vitro. AA-stimulated trypomastigotes released high amounts of prostaglandin E2
(PGE2) and showed PGE2 synthase expression. Raman spectroscopy demonstrated
increased unsaturated lipid content and AA incorporation in stimulated parasites.
Moreover, both Raman and MALDI mass spectroscopy revealed increased AA content in
LBs purified from AA-stimulated parasites compared to LBs from unstimulated
group. By using a specific technique for eicosanoid detection, we immunolocalized
PGE2 within LBs from AA-stimulated trypomastigotes. Altogether, our findings
demonstrate that LBs from the parasite Trypanosoma cruzi are not just lipid
storage inclusions but dynamic organelles, able to respond to host interaction
and inflammatory events and involved in the AA metabolism. Acting as sources of
PGE2, a potent immunomodulatory lipid mediator that inhibits many aspects of
innate and adaptive immunity, newly-formed parasite LBs may be implicated with
the pathogen survival in its host.
PMID- 27490665
TI - Effect of Halide Composition on the Photochemical Stability of Perovskite
Photovoltaic Materials.
AB - The photochemical stability of encapsulated films of mixed halide perovskites
with a range of MAPb(I1-x Brx )3 (MA=methylammonium) compositions (solid
solutions) was investigated under accelerated stressing using concentrated
sunlight. The relevance of accelerated testing to standard operational conditions
of solar cells was confirmed by comparison to degradation experiments under
outdoor sunlight exposure. We found that MAPbBr3 films exhibited no degradation,
while MAPbI3 and mixed halide MAPb(I1-x Brx )3 films decomposed yielding
crystallization of inorganic PbI2 accompanied by degradation of the perovskite
solar light absorption, with faster absorption degradation in mixed halide films.
The crystal coherence length was found to correlate with the stability of the
films. We postulate that the introduction of Br into the mixed halide solid
solution stressed its structure and induced more structural defects and/or grain
boundaries compared to pure halide perovskites, which might be responsible for
the accelerated degradation. Hence, the cause for accelerated degradation may be
the increased defect density rather than the chemical composition of the
perovskite materials.
PMID- 27490666
TI - Medical-Grade Channel Access and Admission Control in 802.11e EDCA for Healthcare
Applications.
AB - In this paper, we deal with the problem of assuring medical-grade quality of
service (QoS) for real-time medical applications in wireless healthcare systems
based on IEEE 802.11e. Firstly, we show that the differentiated channel access of
IEEE 802.11e cannot effectively assure medical-grade QoS because of priority
inversion. To resolve this problem, we propose an efficient channel access
algorithm. The proposed algorithm adjusts arbitrary inter-frame space (AIFS) in
the IEEE 802.11e protocol depending on the QoS measurement of medical traffic, to
provide differentiated near-absolute priority for medical traffic. In addition,
based on rigorous capacity analysis, we propose an admission control scheme that
can avoid performance degradation due to network overload. Via extensive
simulations, we show that the proposed mechanism strictly assures the medical
grade QoS and improves the throughput of low-priority traffic by more than
several times compared to the conventional IEEE 802.11e.
PMID- 27490667
TI - Limb girdle muscular dystrophies: classification, clinical spectrum and emerging
therapies.
AB - PURPOSE OF REVIEW: The aim of the study was to describe the clinical spectrum of
limb girdle muscular dystrophies (LGMDs), the pitfalls of the current
classification system for LGMDs, and emerging therapies for these conditions.
RECENT FINDINGS: Close to half of all LGMD subtypes have been discovered within
the last 6 years of the 21-year-period in which the current classification system
for LGMD has existed. The number of letters for annotation of new recessive LGMD
conditions is exhausted, and multiple already classified LGMDs do not strictly
fulfill diagnostic criteria for LGMD or are registered in other classification
systems for muscle disease. On the contrary, diseases that fulfill classical
criteria for LGMD have found no place in the LGMD classification system. These
shortcomings call for revision/creation of a new classification system for LGMD.
The rapidly expanding gene sequencing capabilities have helped to speed up new
LGMD discoveries, and unveiled pheno-/genotype relations. Parallel to this
progress in identifying new LGMD subtypes, emerging therapies for LGMDs are under
way, but no disease-specific treatment is yet available for nonexperimental use.
SUMMARY: The field of LGMD is rapidly developing from a diagnostic and
therapeutic viewpoint, but a uniform and universally agreed classification system
for LGMDs is needed.
PMID- 27490668
TI - Treatment of Humeral Shaft Fractures: A Critical Analysis Review.
PMID- 27490670
TI - Advances in Pediatric Limb Lengthening: Part 2.
PMID- 27490669
TI - Recommendations for Perioperative Management of Patients on Existing
Anticoagulation Therapy.
PMID- 27490671
TI - Arthroscopic Treatment of Cam-Type Impingement of the Hip.
PMID- 27490672
TI - Prophylaxis Against Venous Thromboembolism After Total Hip and Knee Arthroplasty:
A Critical Analysis Review.
PMID- 27490673
TI - Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation
in Alzheimer's Disease.
AB - The rate of reconfiguration-or intramolecular diffusion-of monomeric Alzheimer
(Abeta) peptides is measured and, under conditions that aggregation is more
likely, peptide diffusion slows down significantly, which allows bimolecular
associations to be initiated. By using the method of Trp-Cys contact quenching,
the rate of reconfiguration is observed to be about five times faster for Abeta40
, which aggregates slowly, than that for Abeta42 , which aggregates quickly.
Furthermore, the rate of reconfiguration for Abeta42 speeds up at higher pH,
which slows aggregation, and in the presence of the aggregation inhibitor
curcumin. The measured reconfiguration rates are able to predict the early
aggregation behavior of the Abeta peptide and provide a kinetic basis for why
Abeta42 is more prone to aggregation than Abeta40 , despite a difference of only
two amino acids.
PMID- 27490674
TI - Estimating Retinal Blood Flow Velocities by Optical Coherence Tomography.
AB - Importance: While optical coherence tomography (OCT) angiography has been
considered to evaluate retinal capillary blood flow instead of fluorescein
angiography, the reflectance pattern of blood vessels on structural OCT might
also provide retinal capillary flow data in the absence of fluorescein
angiography. This potential has been insufficiently explored, despite promising
data concerning a possible relationship between the reflectance pattern of blood
vessels and their perfusion velocity in a laboratory setting. Objective: To
evaluate the potential of retinal blood flow velocity estimation by structural
OCT. Design, Setting, and Participants: Cross-sectional observational study
conducted from June to November 2015 at a tertiary clinical referral center.
Sixty arteries (the superior and inferior temporal arteries) from 30 eyes of 30
patients (17 female, 13 male) were included in the study. Main Outcomes and
Measures: Based on the intraluminal contrast patterns of retinal arteries on OCT,
3 independent graders categorized the blood flow velocities as low, medium, or
high. These results and the results from a software-based intraluminal contrast
analysis were compared with the retinal blood flow velocities measured by video
fluorescein angiography. Results: Among the 30 eyes of 30 patients (mean [SD]
age, 72.6 [12.3] years; 17 female, 13 male), 15 were controls without retinal
occlusion, 6 had a branch retinal artery occlusion, and 9 had a central retinal
artery occlusion. When discriminating between low flow velocities and medium or
high flow velocities, the graders' sensitivity ranged from 88.2% to 100% (grader
1: 88.2%; 95% CI, 63.6%-98.5%; grader 2: 88.2%; 95% CI, 63.6%-98.5%; and grader
3: 100%; 95% CI, 69.8%-100%) and their specificity ranged from 97.6% to 100%
(grader 1: 100%; 95% CI, 87.7%-100%; grader 2: 97.6%; 95% CI, 87.4%-99.9%; and
grader 3: 100%; 95% CI, 87.7%-100%). The kappa coefficients of the comparison
between the 3 graders and the angiography were 0.77 (95% CI, 0.60-0.93; P <
.001), 0.64 (95% CI, 0.44-0.83; P < .001), and 0.87 (95% CI, 0.74-0.99; P <
.001). In the computer-based assessment, the contrast reduction of the
intraluminal pattern could be numerically expressed in a specific coefficient in
the model (I2, describing the angular change of the backscattering intensity in
the model), which presented nonoverlapping intervals between low flow velocities
and medium or high flow velocities (mean [SD] I2, 0.3 [5.3], 20.4 [6.4], and 21.7
[4.0], respectively). Conclusions and Relevance: This study suggests that a low
retinal blood flow velocity reflects in a visually distinct contrast reduction of
the intraluminal pattern of retinal vessels on OCT. Larger studies are required
to assess the clinical benefits.
PMID- 27490675
TI - Cell Surface Proteome of Dental Pulp Stem Cells Identified by Label-Free Mass
Spectrometry.
AB - Multipotent mesenchymal stromal cells (MSCs) are promising tools for regenerative
medicine. They can be isolated from different sources based on their plastic
adherence property. The identification of reliable cell surface markers thus
becomes the Holy Grail for their prospective isolation. Here, we determine the
cell surface proteomes of human dental pulp-derived MSCs isolated from single
donors after culture expansion in low (2%) or high (10%) serum-containing media.
Cell surface proteins were tagged on intact cells using cell impermeable,
cleavable sulfo-NHS-SS-biotin, which allows their enrichment by streptavidin pull
down. For the proteomic analyses, we first compared label-free methods to analyze
cell surface proteomes i.e. composition, enrichment and proteomic differences,
and we developed a new mathematical model to determine cell surface protein
enrichment using a combinatorial gene ontology query. Using this workflow, we
identified 101 cluster of differentiation (CD) markers and 286 non-CD cell
surface proteins. Based on this proteome profiling, we identified 14 cell surface
proteins, which varied consistently in abundance when cells were cultured under
low or high serum conditions. Collectively, our analytical methods provide a
basis for identifying the cell surface proteome of dental pulp stem cells
isolated from single donors and its evolution during culture or differentiation.
Our data provide a comprehensive cell surface proteome for the precise
identification of dental pulp-derived MSC populations and their isolation for
potential therapeutic intervention.
PMID- 27490676
TI - A delayed foreign body granuloma associated with polypropylene sutures used in
tendon transfer. A case report.
AB - INTRODUCTION: A delayed foreign body reaction to polypropylene sutures has not
been previously reported following tendon repair. PRESENTATION OF CASE: A 12-year
old boy underwent tendon transfer. Tendon repair was done using polypropylene
sutures. Five months later, a slowly growing granuloma was seen at the tendon
repair site. Skin testing did not show an allergic reaction to the suture.
Excision of the granuloma and removal of sutures were curative. Histology
confirmed a foreign body granuloma. DISCUSSION: A mass developing several months
at the site of tendon repair indicates either an allergic or foreign body
reaction to the suture. Skin testing (for allergy) and histological examination
of the mass differentiate allergic from foreign body reactions. CONCLUSION: We
report on a rare case of a giant granuloma caused by a delayed foreign body
reaction to polypropylene sutures used in tendon repair.
PMID- 27490677
TI - Isolated rectus abdominis metastasis from melanoma-An extremely rare case.
AB - INTRODUCTION: Melanoma is a health problem world-wide. Its incidence has tripled
in the last decade. The main cause of death in melanoma patients is widespread
metastases. It can metastasize to almost every organ. However, melanoma skeletal
muscle metastases (MSMM) are exceptional, and only two cases of MSMM to rectus
abdominis muscles have been previously published. Regardless of all new advances
seen in melanoma therapy, cure for most MSMM is still elusive. Surgical
approaches are still not well defined. PRESENTATION OF CASE: A 35-year-old woman
had been previously operated of an ulcerated scapular melanoma (Clark level III,
Breslow 2.3mm) in January 2014. Subsequently she underwent a sentinel lymph node
which resulted negative. Twenty months later, a CT scan revealed a well-enhanced
nodule of 25mm in the right rectus abdominis, without any other metastases. The
PET-CT uptake was pathologic (SUV maximum of 13.16). An ultrasound-guided biopsy
confirmed it was a metastatic melanoma. A radical compartmental resection of the
right rectus abdominis muscle was performed. The abdominal wall was reconstructed
with two polypropylene meshes buried preperitoneally. The final histologic
diagnosis of the specimen proved to be a metastasis of melanoma. DISCUSSION:
Surgery is the only potentially curative therapy for patients with isolated MSMM.
The ultimate goal of negative resection margins, in order to avoid local
recurrences, is paramount in those difficult cases. CONCLUSION: Radical
compartmental surgery should be considered for selected stage IV melanoma
patients whose disease could be amenable to complete resection, in order to
extend median survival.
PMID- 27490678
TI - Total vertebrectomy (Th2) and dissection of the subclavian artery for a superior
sulcus tumor invading the spine: A case report.
AB - INTRODUCTION: Surgery for primary lung cancer invading the spine remains
challenging. Here, we present a case of superior sulcus tumor (SST) with
vertebral invasion, successfully resected with total vertebrectomy (Th2) and
dissection of involved apical chest wall and the subclavian artery (SCA).
PRESENTATION OF CASE: A 62-year-old man was referred with the diagnosis of lung
squamous cell carcinoma originating from left upper lobe (clinical stage
IIIA/T4N0M0) involving the thoracic vertebrae (Th2) as well as the apical chest
wall including three ribs (1st, 2nd and 3rd) and SCA. After induction concurrent
chemo-radiotherapy, we achieved complete resection by three-step surgical
procedures as follows: first, the anterior portion of involved chest wall
including SCA was dissected through the trans-manubrial approach (TMA); next, the
posterior portion of involved chest wall including ribs was dissected and left
upper lobectomy with nodal dissection was performed through posterolateral
thoracotomy; finally, total vertebrectomy (Th2) was performed through posterior
mid-line approach. DISCUSSION: This tumor was existence of anterior and posterior
position in pulmonary apex region. So that, it is very important for complete
resecting this complicated tumor to work out operation's strategy. CONCLUSION:
Surgery may be indicated for SST invading the spine, when complete resection is
expected.
PMID- 27490679
TI - A case of abdominal compartment syndrome derived from simple elongated sigmoid
colon in an elderly man.
AB - INTRODUCTION: Abdominal compartment syndrome or intra-abdominal hypertension may
occur after intra-abdominal events, but their etiology and clinical signs remain
unclear. We report a case of abdominal compartment syndrome in an elderly patient
without other risk factors. PRESENTATION OF CASE: An 86-year-old man had been
admitted to our hospital several times for a dilated sigmoid colon with
elongation, and had complained about abdominal pain and abdominal fullness. At
every admission we decompressed the sigmoid colon gas by colonoscopy, resulting
in early discharge the following day. Recently, the patient developed dementia
and experienced reduced activities of daily living that are common with aging. He
frequently complained of severe abdominal distension with hypotension,
tachycardia and tachypnea, and finally entered hospital twice a week. We decided
to perform elective surgery, which showed abdominal compartment syndrome caused
by elongated sigmoid colon without volvulus (the first reported case). DISCUSSION
AND CONCLUSION: Considering the increase in the aging population, we must bear in
mind that abdominal compartment syndrome may occur in simple elongated sigmoid
colon without other risk factors.
PMID- 27490680
TI - A new hybrid sutureless patch repair utilizing chitosan for left ventricle
rupture after myocardial infarction: A case report.
AB - INTRODUCTION: There are many publications reporting the use of TachoSil sheets
for sutureless repair. Trauma doctors have recently reported that chitosan-based
sheets can efficiently achieve hemostasis for active bleeding. PRESENTATION OF
CASE: An 85-year-old man was diagnosed with left ventricle free wall rupture that
caused cardiac tamponade and cardiogenic shock. Extracorporeal membrane
oxygenator (ECMO) was started immediately and surgical repair was planned.
Bleeding occurred from a 1-cm tear in the center of the necrotic area in the
territory of the left circumflex artery. The tear was treated with a chitosan
based HemCon Bandage. After hemostasis of the myocardium was achieved, the
bandage was peeled off and a patch repair was performed using collagen fleece
with fibrinogen-based impregnation. His condition subsequently improved. The
tracheal tube was extubated and ECMO was removed 2days after the surgery. One
month later, the patient had no complications at his postoperative follow-up
visit. DISCUSSION: To our knowledge, this is the first report of a hybrid patch
repair utilizing chitosan-based sheets for a left ventricle rupture after
myocardial infarction. Further studies are necessary to evaluate the short- and
long-term efficacy of this procedure, and these results must be compared with
those of classical surgical repairs. CONCLUSION: The new hybrid sutureless patch
utilizing chitosan was demonstrated as safe, easy and effective.
PMID- 27490682
TI - General and Mild Cobalt-Catalyzed C-Alkylation of Unactivated Amides and Esters
with Alcohols.
AB - The borrowing hydrogen or hydrogen autotransfer methodology is an elegant and
sustainable or green concept to construct carbon-carbon bonds. In this concept,
alcohols, which can be obtained from barely used and indigestible biomass, such
as lignocellulose, are employed as alkylating reagents. An especially challenging
alkylation is that of unactivated esters and amides. Only noble metal catalysts
based on iridium and ruthenium have been used to accomplish these reactions.
Herein, we report on the first base metal-catalyzed alpha-alkylation of
unactivated amides and esters by alcohols. Cobalt complexes stabilized with
pincer ligands, recently developed in our laboratory, catalyze these reactions
very efficiently. The precatalysts can be synthesized easily from commercially
available starting materials on a multigram scale and are self-activating under
the basic reaction conditions. This Co catalyst class is also able to mediate
alkylation reactions of both esters and amides. In addition, we apply the
methodology to synthesize ketones and to convert alcohols into aldehydes
elongated by two carbon atoms.
PMID- 27490681
TI - Two cases of laparoscopic simultaneous resection of colorectal cancer and
synchronous liver metastases in elderly patients.
AB - INTRODUCTION: The laparoscopic resection of colorectal cancer and laparoscopic
liver surgery are widely considered to be safe. Recently, it has been reported
that the simultaneous laparoscopic resection of primary colorectal cancer and
liver metastasis is technically feasible and safe when it is performed at
experienced centers. However, the feasibility of simultaneous laparoscopic
procedures for colorectal cancer and synchronous colorectal liver metastases in
elderly patients has not been studied sufficiently. In this study, two cases in
which elderly patients with colorectal cancer and synchronous liver metastases
were treated with simultaneous laparoscopic resection are reported. PRESENTATION
OF CASES: An 83-year-old female was diagnosed with ascending colon cancer and
synchronous hepatic metastases. Simultaneous laparoscopic resection of the
primary colon cancer and the liver metastasis was performed. Another tiny hepatic
metastasis was subsequently detected in the right hepatic lobe. It was treated
with hand-assisted radiofrequency ablation (RFA). The total operative time was
470min, and 340g of intraoperative blood loss occurred. The other case involved a
78-year-old male who was diagnosed with ascending colon cancer and synchronous
hepatic metastasis in the right hepatic lobe. Simultaneous laparoscopic resection
of the primary colon tumor and liver metastasis was performed. The total
operative time was 471min, and 240g of intraoperative blood loss occurred. The
postoperative courses of both patients were uneventful. DISCUSSION AND
CONCLUSION: Our results indicate that simultaneous laparoscopic resection of
colorectal cancer and synchronous liver metastases is feasible and safe in
elderly patients.
PMID- 27490684
TI - Use of Cepheid Xpert Carba-R(r) for Rapid Detection of Carbapenemase-Producing
Bacteria in Abdominal Septic Patients Admitted to Intensive Care Unit.
AB - Early institution of effective antibiotic therapy and source control are pivotal
to improve survival of abdominal septic patients. Xpert(r) Carba-R is a real time
polymerase chain reaction assay for rapid detection and differentiation of five
genes (blaKPC, blaVIM, blaOXA-48, blaIMP-1, blaNDM) responsible for carbapenem
resistance. We performed an observational study investigating the clinical
usefulness and applicability of Xpert(r) Carba-R to detect carbapenem resistance
in abdominal septic patients admitted to intensive care unit. We compared the
results of Xpert(r) Carba-R with standard microbiological culture. We collected a
set of two rectal/stomia swabs and two swabs from abdominal drainage fluid for
each patient. We included 20 patients for a total of 45 comparisons between the
two methods. In our clinical setting, the overall performance of Xpert(r) Carba-R
for detection of carbapenem resistance in the presence of genes detectable and
non-detectable by the method was: sensitivity 50% (95% CI 24.6-75.3); specificity
93.1% (95% CI 77.2-99.1); positive predictive value (PPV) 80% (95% CI 44.4-97.5);
negative predictive value (NPV) 77.1% (95% CI 56.9-89.6). The inter-rater
agreement was 0.47 (SE 0.14; 95% CI 0.20-0.74). When considering the only 5
mechanisms of resistance detected by both methods, the overall diagnostic
performance was: sensitivity 100% (95% CI 69.1-100), specificity 94.2 (95% CI
80.8-99.3), PPV 83.3 (95% CI 59.6-97.9) and NPV 100% (95% CI 89.4-100). The inter
rater agreement was 0.88 (SE 0.08; 95% CI 0.71-1). Xpert(r) Carba-R may be
considered an additional diagnostic tool for early diagnosis of carbapenem
resistance in abdominal septic patients. Clinicians should be aware of their
epidemiology before its introduction in the diagnostic protocol of their
intensive care units.
PMID- 27490685
TI - Biomarkers for Presymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer
Patients.
AB - Cardiotoxicity of doxorubicin (DOX) remains an important health concern. DOX
cardiotoxicity is cumulative-dose-dependent and begins with the first dose of
chemotherapy. No biomarker for presymptomatic detection of DOX cardiotoxicity has
been validated. Our hypothesis is that peripheral blood cells (PBC) gene
expression induced by the early doses of DOX-based chemotherapy could identify
potential biomarkers for presymptomatic cardiotoxicity in cancer patients. PBC
gene expression of 33 breast cancer patients was conducted before and after the
first cycle of DOX-based chemotherapy. Cardiac function was evaluated before the
start of chemotherapy and at its completion. Differentially expressed genes (DEG)
of patients who developed DOX-associated cardiotoxicity after the completion of
chemotherapy were compared with DEG of patients who did not. Ingenuity database
was used for functional analysis of DEG. Sixty-sevens DEG (P<0.05) were
identified in PBC of patients with DOX-cardiotoxicity. Most of DEG encode
proteins secreted by activated neutrophils. The functional analysis of the DEG
showed enrichment for immune- and inflammatory response. This is the first study
to identify the PBC transcriptome signature associated with a single dose of DOX
based chemotherapy in cancer patients. We have shown that PBC transcriptome
signature associated with one dose of DOX chemotherapy in breast cancer can
predict later impairment of cardiac function. This finding may be of value in
identifying patients at high or low risk for the development of DOX
cardiotoxicity during the initial doses of chemotherapy and thus to avoid the
accumulating toxic effects from the subsequent doses during treatment.
PMID- 27490687
TI - The Femoral Intercondylar Notch During Life: An Anatomic Redefinition With
Patterns Predisposing to Cruciate Ligament Impingement.
AB - OBJECTIVE: The goals of this study were to test whether age- and sex-dependent
variations in the size and shape of the intercondylar notch exist and to define
the landmarks and measurements best suited for assessment of the intercondylar
notch on MR images. MATERIALS AND METHODS: In this retrospective cross-sectional
study, 329 patients were divided into six age groups, and their MR images (3-T
coronal T2-weighted fat-suppressed spectral attenuated inversion recovery
[SPAIR], sagittal proton density-weighted, axial T2-weighted fat-suppressed
SPAIR) were evaluated. The intercondylar notch was measured and its shape
evaluated on coronal images. Three shapes of intercondylar notch were defined.
RESULTS: The intercondylar notch is subject to change throughout life, narrowing
more distally and widening more proximally. Its width ranges from 16.23 +/- 2.71
mm before the age of 11 years to 19.38 +/- 2.90 mm in middle age and then
decreases to 18.6 +/- 2.36 mm after the age of 60 years. Its shape changes from
an A shape in the early stages of life to an Omega shape in the later stages.
CONCLUSION: The term "intercondylar space" is introduced as a morphologic
description of the osseous intercondylar notch and adjacent structures. The femur
as a whole is subject to substantial plastic deformation throughout life, not
only in its proximal part, with respect to torsion, but also in its distal
extent.
PMID- 27490686
TI - Neuroimaging of the bilingual brain: Structural brain correlates of listening and
speaking in a second language.
AB - Diffusion tensor imaging was used to compare white matter structure between
American monolingual and Spanish-English bilingual adults living in the United
States. In the bilingual group, relationships between white matter structure and
naturalistic immersive experience in listening to and speaking English were
additionally explored. White matter structural differences between groups were
found to be bilateral and widespread. In the bilingual group, experience in
listening to English was more robustly correlated with decreases in radial and
mean diffusivity in anterior white matter regions of the left hemisphere, whereas
experience in speaking English was more robustly correlated with increases in
fractional anisotropy in more posterior left hemisphere white matter regions. The
findings suggest that (a) foreign language immersion induces neuroplasticity in
the adult brain, (b) the degree of alteration is proportional to language
experience, and (c) the modes of immersive language experience have more robust
effects on different brain regions and on different structural features.
PMID- 27490688
TI - IMAGING DIAGNOSIS-COMPUTED TOMOGRAPHY OF TRACTION BRONCHIECTASIS SECONDARY TO
PULMONARY FIBROSIS IN A PATTERDALE TERRIER.
AB - An 8-year-old, Patterdale terrier was referred for evaluation of tachypnoea,
exercise intolerance, and weight loss. Computed tomographic images showed
pneumomediastinum, diffuse pulmonary ground glass opacity, and marked dilatation
of peripheral bronchi, but no evidence of thickened bronchial walls. The
histopathologic diagnosis was diffuse pulmonary interstitial fibrosis, type II
pneumocyte hyperplasia, and bronchiectasis. The lack of evidence of primary
bronchitis supported a diagnosis of traction bronchiectasis. Traction
bronchiectasis can occur as a sequela to pulmonary fibrosis in dogs.
PMID- 27490689
TI - Proton-Coupled Electron Transfer in a Series of Ruthenium-Linked Tyrosines with
Internal Bases: Evaluation of a Tunneling Model for Experimental Temperature
Dependent Kinetics.
AB - Photoinitiated proton-coupled electron transfer (PCET) kinetics has been
investigated in a series of four modified tyrosines linked to a ruthenium
photosensitizer in acetonitrile, with each tyrosine bearing an internal hydrogen
bond to a covalently linked pyridine or benzimidazole base. After correcting for
differences in driving force, it is found that the intrinsic PCET rate constant
still varies by 2 orders of magnitude. The differences in rates, as well as the
magnitude of the kinetic isotope effect (KIE = kH/kD), both generally correlate
with DFT calculated proton donor-acceptor distances. An Arrhenius analysis of
temperature dependent data shows that the difference in reactivity arises
primarily from differences in activation energies. We use this kinetic data to
evaluate a commonly employed theoretical model for proton tunneling which
includes a harmonic distribution of proton donor-acceptor distances due to
vibrational motions of the molecule. Applying this model to the experimental data
yields the conclusion that donor-acceptor compression is more facile in the
compounds with shorter PT distance; however, this is contrary to independent
calculations for the same compounds. This discrepancy is likely because the
assumption in the model of Morse-shaped proton potential energy surfaces is
inappropriate for (strongly) hydrogen-bonded systems. These results question the
general applicability of this model. The results also suggest that a correlation
of rate vs proton tunneling distance for the series of compounds is complicated
by a concomitant variation of other relevant parameters.
PMID- 27490691
TI - Steric and Electronic Influence on Proton-Coupled Electron-Transfer Reactivity of
a Mononuclear Mn(III)-Hydroxo Complex.
AB - A mononuclear hydroxomanganese(III) complex was synthesized utilizing the N5
amide-containing ligand 2-[bis(pyridin-2-ylmethyl)]amino-N-2-methyl-quinolin-8-yl
acetamidate (dpaq(2Me) ). This complex is similar to previously reported
[Mn(III)(OH)(dpaq(H))](+) [Inorg. Chem. 2014, 53, 7622-7634] but contains a
methyl group adjacent to the hydroxo moiety. This alpha-methylquinoline group in
[Mn(III)(OH)(dpaq(2Me))](+) gives rise to a 0.1 A elongation in the Mn
N(quinoline) distance relative to [Mn(III)(OH)(dpaq(H))](+). Similar bond
elongation is observed in the corresponding Mn(II) complex. In MeCN,
[Mn(III)(OH)(dpaq(2Me))](+) reacts rapidly with 2,2',6,6'-tetramethylpiperidine-1
ol (TEMPOH) at -35 degrees C by a concerted proton-electron transfer (CPET)
mechanism (second-order rate constant k2 of 3.9(3) M(-1) s(-1)). Using enthalpies
and entropies of activation from variable-temperature studies of TEMPOH oxidation
by [Mn(III)(OH)(dpaq(2Me))](+) (DeltaH(?) = 5.7(3) kcal(-1) M(-1); DeltaS(?) =
41(1) cal M(-1) K(-1)), it was determined that [Mn(III)(OH)(dpaq(2Me))](+)
oxidizes TEMPOH ~240 times faster than [Mn(III)(OH)(dpaq(H))](+). The
[Mn(III)(OH)(dpaq(2Me))](+) complex is also capable of oxidizing the stronger O-H
and C-H bonds of 2,4,6-tri-tert-butylphenol and xanthene, respectively. However,
for these reactions [Mn(III)(OH)(dpaq(2Me))](+) displays, at best, modest rate
enhancement relative to [Mn(III)(OH)(dpaq(H))](+). A combination of density
function theory (DFT) and cyclic voltammetry studies establish an increase in the
Mn(III)/Mn(II) reduction potential of [Mn(III)(OH)(dpaq(2Me))](+) relative to
[Mn(III)(OH)(dpaq(H))](+), which gives rise to a larger driving force for CPET
for the former complex. Thus, more favorable thermodynamics for
[Mn(III)(OH)(dpaq(2Me))](+) can account for the dramatic increase in rate with
TEMPOH. For the more sterically encumbered substrates, DFT computations suggest
that this effect is mitigated by unfavorable steric interactions between the
substrate and the alpha-methylquinoline group of the dpaq(2Me) ligand. The DFT
calculations, which reproduce the experimental activation free energies quite
well, provide the first examination of the transition-state structure of
mononuclear Mn(III)(OH) species during a CPET reaction.
PMID- 27490690
TI - Intra-Animal Comparison between Three-dimensional Molecularly Targeted US and
Three-dimensional Dynamic Contrast-enhanced US for Early Antiangiogenic Treatment
Assessment in Colon Cancer.
AB - Purpose To perform an intra-animal comparison between (a) three-dimensional (3D)
molecularly targeted ultrasonography (US) by using clinical-grade vascular
endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles and (b) 3D
dynamic contrast material-enhanced (DCE) US by using nontargeted microbubbles for
assessment of antiangiogenic treatment effects in a murine model of human colon
cancer. Materials and Methods Twenty-three mice with human colon cancer
xenografts were randomized to receive either single-dose antiangiogenic treatment
(bevacizumab, n = 14) or control treatment (saline, n = 9). At baseline and 24
hours after treatment, animals were imaged with a clinical US system equipped
with a clinical matrix array transducer by using the following techniques: (a)
molecularly targeted US with VEGFR2-targeted microbubbles, (b) bolus DCE US with
nontargeted microbubbles, and (c) destruction-replenishment DCE US with
nontargeted microbubbles. VEGFR2-targeted US signal, peak enhancement, area under
the time-intensity curve, time to peak, relative blood volume (rBV), relative
blood flow, and blood flow velocity were quantified. VEGFR2 expression and
percentage area of blood vessels were assessed ex vivo with quantitative
immunofluorescence and correlated with corresponding in vivo US parameters.
Statistical analysis was performed with Wilcoxon signed rank tests and rank sum
tests, as well as Pearson correlation analysis. Results Molecularly targeted US
signal with VEGFR2-targeted microbubbles, peak enhancement, and rBV significantly
decreased (P <= .03) after a single antiangiogenic treatment compared with those
in the control group; similarly, ex vivo VEGFR2 expression (P = .03) and
percentage area of blood vessels (P = .03) significantly decreased after
antiangiogenic treatment. Three-dimensional molecularly targeted US signal
correlated well with VEGFR2 expression (r = 0.86, P = .001), and rBV (r = 0.71, P
= .01) and relative blood flow (r = 0.78, P = .005) correlated well with
percentage area of blood vessels, while other US perfusion parameters did not.
Conclusion Three-dimensional molecularly targeted US and destruction
replenishment 3D DCE US provide complementary molecular and functional in vivo
imaging information on antiangiogenic treatment effects in human colon cancer
xenografts compared with ex vivo reference standards. (c) RSNA, 2016 Online
supplemental material is available for this article.
PMID- 27490692
TI - Copula-Based Approach to Synthetic Population Generation.
AB - Generating synthetic baseline populations is a fundamental step of agent-based
modeling and simulation, which is growing fast in a wide range of socio-economic
areas including transportation planning research. Traditionally, in many
commercial and non-commercial microsimulation systems, the iterative proportional
fitting (IPF) procedure has been used for creating the joint distribution of
individuals when combining a reference joint distribution with target marginal
distributions. Although IPF is simple, computationally efficient, and rigorously
founded, it is unclear whether IPF well preserves the dependence structure of the
reference joint table sufficiently when fitting it to target margins. In this
paper, a novel method is proposed based on the copula concept in order to provide
an alternative approach to the problem that IPF resolves. The dependency
characteristic measures were computed and the results from the proposed method
and IPF were compared. In most test cases, the proposed method outperformed IPF
in preserving the dependence structure of the reference joint distribution.
PMID- 27490693
TI - Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across
Cancer Types.
AB - Disruption of gene regulation is known to play major roles in carcinogenesis and
tumour progression. Here, we comprehensively characterize the mutational profiles
of diverse transcription factor binding sites (TFBSs) across 1,574 completely
sequenced cancer genomes encompassing 11 tumour types. We assess the relative
rates and impact of the mutational burden at the binding sites of 81
transcription factors (TFs), by comparing the abundance and patterns of single
base substitutions within putatively functional binding sites to control sites
with matched sequence composition. There is a strong (1.43-fold) and significant
excess of mutations at functional binding sites across TFs, and the mutations
that accumulate in cancers are typically more disruptive than variants tolerated
in extant human populations at the same sites. CTCF binding sites suffer an
exceptionally high mutational load in cancer (3.31-fold excess) relative to
control sites, and we demonstrate for the first time that this effect is seen in
essentially all cancer types with sufficient data. The sub-set of CTCF sites
involved in higher order chromatin structures has the highest mutational burden,
suggesting a widespread breakdown of chromatin organization. However, we find no
evidence for selection driving these distinctive patterns of mutation. The
mutational load at CTCF-binding sites is substantially determined by replication
timing and the mutational signature of the tumor in question, suggesting that
selectively neutral processes underlie the unusual mutation patterns. Pervasive
hyper-mutation within transcription factor binding sites rewires the regulatory
landscape of the cancer genome, but it is dominated by mutational processes
rather than selection.
PMID- 27490694
TI - AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid
Induced Cytotoxicity by Restoring the NOS-3 Expression.
AB - The harmful effects of bile acid accumulation occurring during cholestatic liver
diseases have been associated with oxidative stress increase and endothelial
nitric oxide synthase (NOS-3) expression decrease in liver cells. We have
previously reported that glycochenodeoxycholic acid (GCDCA) down-regulates gene
expression by increasing SP1 binding to the NOS-3 promoter in an oxidative stress
dependent manner. In the present study, we aimed to investigate the role of
transcription factor (TF) AP-1 on the NOS-3 deregulation during GCDCA-induced
cholestasis. The cytotoxic response to GCDCA was characterized by 1) the
increased expression and activation of TFs cJun and c-Fos; 2) a higher binding
capability of these at position -666 of the NOS-3 promoter; 3) a decrease of the
transcriptional activity of the promoter and the expression and activity of NOS
3; and 4) the expression increase of cyclin D1. Specific inhibition of AP-1 by
the retinoid SR 11302 counteracted the cytotoxic effects induced by GCDCA while
promoting NOS-3 expression recovery and cyclin D1 reduction. NOS activity
inhibition by L-NAME inhibited the protective effect of SR 11302. Inducible NOS
isoform was no detected in this experimental model of cholestasis. Our data
provide direct evidence for the involvement of AP-1 in the NOS-3 expression
regulation during cholestasis and define a critical role for NOS-3 in regulating
the expression of cyclin D1 during the cell damage induced by bile acids. AP-1
appears as a potential therapeutic target in cholestatic liver diseases given its
role as a transcriptional repressor of NOS-3.
PMID- 27490696
TI - Modification of human serum albumin by the nerve agent VX: microbore liquid
chromatography/electrospray ionization high-resolution time-of-flight tandem mass
spectrometry method for detection of phosphonylated tyrosine and novel cysteine
containing disulfide adducts.
AB - RATIONALE: Organophosphorus nerve agents still constitute a considerable threat
to the health of military personnel and the civilian population. Long-term
biomarkers are crucial for reliable verification of exposure to banned
substances. Therefore, current research focuses on identification of endogenous
protein targets showing covalent modifications by organophosphorus nerve agents
(adducts). METHODS: Purified human serum albumin and human plasma were incubated
with the nerve agent VX followed by enzymatic proteolysis with pronase. Resulting
peptide cleavage products were separated by microbore liquid chromatography
(MULC) online coupled to positive electrospray ionization (ESI) with subsequent
high-resolution time-of-flight tandem mass spectrometry (HR MS/MS) allowing
identification of known and novel adducts. RESULTS: In addition to known
phosphonylation of various tyrosine residues, albumin was found to be modified at
diverse cysteine residues by covalent attachment of the leaving group of VX.
These novel disulfide adducts were cleaved from at least two regions of the
intact protein as dipeptides containing cysteine and proline either as CP or PC.
A rapid and sensitive method was developed for simultaneous detection of the
diverse covalent modifications of human albumin by VX. CONCLUSIONS:
Identification of the novel leaving group adducts with human albumin expands the
basic knowledge on molecular toxicology of the nerve agent VX. Furthermore, the
presented MULC/ESI HR MS/MS method might be of relevance for verification of VX
poisoning. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27490695
TI - Nosocomial Outbreak of OXA-48-Producing Klebsiella pneumoniae in a Chinese
Hospital: Clonal Transmission of ST147 and ST383.
AB - BACKGROUND: In China, the spread and outbreak of OXA-48-producing
Enterobacteriaceae remains largely unknown. METHODS: OXA-48-producing isolates
were analyzed for genetic relatedness by pulsed-field gel electrophoresis (PFGE),
antimicrobial susceptibility by E-test, and sequence type (ST) by multilocus
sequence typing. S1-PFGE and southern blotting were used for plasmid profiling,
and PCR and subsequent sequencing were performed to determine the genetic
environment of blaOXA-48 gene. RESULTS: In total, 37 non-duplicated OXA-48
producing K. pneumoniae (OXAKp) isolates were recovered. From December 2013 to
August 2014, an outbreak was observed at a respiratory ICU. The 37 isolates of K.
pneumoniae were categorized into four PFGE types (A, B, C, and D). The
predominant strains associated with the outbreak were strains with PFGE type A
and B, which belonged to ST383 and ST147, respectively. Plasmid sequencing
revealed that the blaOXA-48-carrying plasmid is 69,069 bp in length and belongs
to the IncL/M incompatibility group. Sequence analysis revealed that the IS1999
element was located upstream of the blaOXA-48 gene and was truncated by IS1R.
CONCLUSIONS: In this study, the dissemination and outbreak of OXAKp isolates were
clonal, and ST147 and ST383 K. pneumoniae were the predominant clones that were
associated with the outbreak. Meanwhile, the horizontal transfer of plasmids
potentially mediate the spread of blaOXA-48 gene between different K. pneumoniae
strains.
PMID- 27490697
TI - petal: Co-expression network modelling in R.
AB - BACKGROUND: Networks provide effective models to study complex biological
systems, such as gene and protein interaction networks. With the advent of new
sequencing technologies, many life scientists are grasping for user-friendly
methods and tools to examine biological components at the whole-systems level.
Gene co-expression network analysis approaches are frequently used to
successfully associate genes with biological processes and demonstrate great
potential to gain further insights into the functionality of genes, thus becoming
a standard approach in Systems Biology. Here the objective is to construct
biologically meaningful and statistically strong co-expression networks, the
identification of research dependent subnetworks, and the presentation of self
contained results. RESULTS: We introduce petal, a novel approach to generate gene
co-expression network models based on experimental gene expression measures.
petal focuses on statistical, mathematical, and biological characteristics of
both, input data and output network models. Often over-looked issues of current
co-expression analysis tools include the assumption of data normality, which is
seldom the case for hight-throughput expression data obtained from RNA-seq
technologies. petal does not assume data normality, making it a statistically
appropriate method for RNA-seq data. Also, network models are rarely tested for
their known typical architecture: scale-free and small-world. petal explicitly
constructs networks based on both these characteristics, thereby generating
biologically meaningful models. Furthermore, many network analysis tools require
a number of user-defined input variables, these often require tuning and/or an
understanding of the underlying algorithm; petal requires no user input other
than experimental data. This allows for reproducible results, and simplifies the
use of petal. Lastly, this approach is specifically designed for very large high
throughput datasets; this way, petal's network models represent as much of the
entire system as possible to provide a whole-system approach. CONCLUSION: petal
is a novel tool for generating co-expression network models of whole-genomics
experiments. It is implemented in R and available as a library. Its application
to several whole-genome experiments has generated novel meaningful results and
has lead the way to new testing hypothesizes for further biological
investigation.
PMID- 27490698
TI - Neutropenia as an Adverse Event following Vaccination: Results from Randomized
Clinical Trials in Healthy Adults and Systematic Review.
AB - BACKGROUND: In the context of early vaccine trials aimed at evaluating the safety
profile of novel vaccines, abnormal haematological values, such as neutropenia,
are often reported. It is therefore important to evaluate how these trials should
be planned not to miss potentially important safety signals, but also to
understand the implications and the clinical relevance. METHODOLOGY: We report
and discuss the results from five clinical trials (two with a new Shigella
vaccine in the early stage of clinical development and three with licensed
vaccines) where the absolute neutrophil counts (ANC) were evaluated before and
after vaccination. Additionally, we have performed a systematic review of the
literature on cases of neutropenia reported during vaccine trials to discuss our
results in a more general context. PRINCIPAL FINDINGS: Both in our clinical
trials and in the literature review, several cases of neutropenia have been
reported, in the first two weeks after vaccination. However, neutropenia was
generally transient and had a benign clinical outcome, after vaccination with
either multiple novel candidates or well-known licensed vaccines. Additionally,
the vaccine recipients with neutropenia frequently had lower baseline ANC than
non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of
African descent, known to have lower ANC compared to western populations.
CONCLUSIONS: It is important to include ANC and other haematological tests in
early vaccine trials to identify potential safety signals. Post-vaccination
neutropenia is not uncommon, generally transient and clinically benign, but many
vaccine trials do not have a sampling schedule that allows its detection. Given
ethnic variability in the level of circulating neutrophils, normal ranges taking
into account ethnicity should be used for determination of trial
inclusion/exclusion criteria and classification of neutropenia related adverse
events. TRIAL REGISTRATION: ClinicalTrials.gov NCT02017899, NCT02034500,
NCT01771367, NCT01765413, NCT02523287.
PMID- 27490699
TI - The Myeloablative Drug Busulfan Converts Cysteine to Dehydroalanine and
Lanthionine in Redoxins.
AB - The myeloablative agent busulfan (1,4-butanediol dimethanesulfonate) is an old
drug that is used routinely to eliminate cancerous bone marrow prior to
hematopoietic stem cell transplant. The myeloablative activity and systemic
toxicity of busulfan have been ascribed to its ability to cross-link DNA. In
contrast, here we demonstrate that incubation of busulfan with the thiol redox
proteins glutaredoxin or thioredoxin at pH 7.4 and 37 degrees C results in the
formation of putative S-tetrahydrothiophenium adducts at their catalytic Cys
residues, followed by beta-elimination to yield dehydroalanine. Both proteins
contain a second Cys, in their catalytic C-X-X-C motif, which reacts with the
dehydroalanine, the initial Cys adduct with busulfan, or the S
tetrahydrothiophenium, to form novel intramolecular cross-links. The reactivity
of the dehydroalanine (DHA) formed is further demonstrated by adduction with
glutathione to yield a lanthionine and by a novel reaction with the reducing
agent tris(2-carboxyethyl)phosphine (TCEP), which yields a phosphine adduct via
Michael addition to the DHA. Formation of a second quaternary organophosphonium
salt via nucleophilic substitution with TCEP on the initial busulfan-protein
adduct or on the THT(+)-Redoxin species is also observed. These results reveal a
rich potential for reactions of busulfan with proteins in vitro, and likely in
vivo. It is striking that several of the chemically altered protein products
retain none of the atoms of busulfan, in contrast to typical drug-protein adducts
or traditional protein modification reagents. In particular, the ability of a
clinically used drug to convert Cys to dehydrolanine in intact proteins, and its
subsequent reaction with biological thiols, is unprecedented.
PMID- 27490700
TI - Clinical Relevance of ASC-H Cytologies: Experience in a Single Tertiary Hospital.
AB - OBJECTIVES: To review the cases of atypical squamous cells (ASC), cannot exclude
squamous intraepithelial lesion (ASC-H) diagnosed at a single institution and to
discuss the interpretation challenges and clinical management of these cases.
STUDY DESIGN: The ASC-H cases diagnosed at our institution from 2006 to 2015 were
studied retrospectively; of 159,000 Pap smears, there were 959 cases of ASC of
undetermined significance (ASC-US) and 148 cases of ASC-H. We have reviewed the
clinical records of the ASC-H cases, and data have been analyzed using SPSS 20.0.
RESULTS: Median age was 43.1 years; 49.6% of the patients had previous cervical
cytologies, and 55.9% of them were negative. Following ASC-H diagnosis, another
smear was obtained in 97.1% of the cases and in 67.6% a biopsy was performed.
Biopsy revealed low-grade dysplasia in 18.8% of the cases, high-grade dysplasia
in 27.8%, and infiltrating carcinoma in 2.3%. Patients with significant lesions
in histology were younger than patients with negative results (p = 0.08). A
diagnosis of ASC-H/squamous intraepithelial lesion in the repeated cytology had a
sensitivity of 74.2%, specificity of 39.6%, positive predictive value of 44.8%,
and negative predictive value of 70% for the diagnosis of dysplasia. CONCLUSIONS:
ASC-H diagnosis is associated with a high incidence of histological high-grade
lesions. A repeat cytology can aid in the selection of high-risk patients, but
there may be false-negative results.
PMID- 27490701
TI - Commentary on USPSTF Final Statement on Universal Screening for Autism.
PMID- 27490702
TI - Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: A
prospective cohort study.
AB - BACKGROUND AND AIM: Liver stiffness measurement using transient elastography
appears to be an excellent tool for detection of liver fibrosis and cirrhosis
with high accuracy. The aim of this study is to evaluate the efficacy of
preoperative liver stiffness measurement in predicting post-hepatectomy liver
failure. METHODS: A prospective cohort study of all consecutive patients
undergoing hepatectomy for hepatocellular carcinoma from February 2010 to August
2014 was studied. All patients received detailed preoperative assessments
including liver stiffness measurement. The primary outcome was post-hepatectomy
liver failure according to the International Study Group of Liver Surgery
definition. RESULTS: A total of 255 patients were included. Liver stiffness
measurement showed significant correlation with grade B or C post-hepatectomy
liver failure. (P = 0.003) Using the cutoff at 12 kPa, liver stiffness
measurement had a sensitivity of 52.4% and specificity of 73.3% in predication of
high-grade (grade B or C) post-hepatectomy liver failure. Liver stiffness
measurement > 12 kPa was also an independent prognostic factor for both high
grade post-hepatectomy liver failure and major postoperative complications by
multivariate analysis. The diagnostic accuracy was better in patients without
right lobe tumor with an area under the receiver operating characteristic of 0.83
compared with an area under the receiver operating characteristic of only 0.62 in
patients with right lobe tumor. CONCLUSIONS: Liver stiffness measurement using
Fibroscan is good to predict high-grade post-hepatectomy liver failure especially
in patients without right lobe tumor.
PMID- 27490703
TI - Gram Scale Synthesis of Benzophenanthroline and Its Blue Phosphorescent Platinum
Complex.
AB - The design, synthesis, and characterization of 12
phenylbenzo[f][1,7]phenanthroline, Bzp, is reported. Its use as a fluorine-free
ligand for sky blue phosphorescence is demonstrated in a cyclometalated platinum
complex, BzpPtDpm. BzpPtDpm phosphoresces at the same wavelength as its analogous
4,6-difluorophenylpyridine complex at both room temperature (466 nm) and 77 K
(458 nm). Finally, production of a conformationally restricted derivative of
BzpPtDpm with greatly increased quantum yield (46%) validates the versatility of
the synthetic route.
PMID- 27490704
TI - Improving Metabolic Pathway Efficiency by Statistical Model-Based Multivariate
Regulatory Metabolic Engineering.
AB - Metabolic engineering entails target modification of cell metabolism to maximize
the production of a specific compound. For empowering combinatorial optimization
in strain engineering, tools and algorithms are needed to efficiently sample the
multidimensional gene expression space and locate the desirable overproduction
phenotype. We addressed this challenge by employing design of experiment (DoE)
models to quantitatively correlate gene expression with strain performance. By
fractionally sampling the gene expression landscape, we statistically screened
the dominant enzyme targets that determine metabolic pathway efficiency. An
empirical quadratic regression model was subsequently used to identify the
optimal gene expression patterns of the investigated pathway. As a proof of
concept, our approach yielded the natural product violacein at 525.4 mg/L in
shake flasks, a 3.2-fold increase from the baseline strain. Violacein production
was further increased to 1.31 g/L in a controlled benchtop bioreactor. We found
that formulating discretized gene expression levels into logarithmic variables
(Linlog transformation) was essential for implementing this DoE-based
optimization procedure. The reported methodology can aid multivariate
combinatorial pathway engineering and may be generalized as a standard procedure
for accelerating strain engineering and improving metabolic pathway efficiency.
PMID- 27490706
TI - Dosing of Milrinone in Preterm Neonates to Prevent Postligation Cardiac Syndrome:
Simulation Study Suggests Need for Bolus Infusion.
AB - BACKGROUND: Milrinone has been suggested as a possible first-line therapy for
preterm neonates to prevent postligation cardiac syndrome (PLCS) through
decreasing systemic vascular resistance and increasing cardiac contractility. The
optimal dosing regimen, however, is not known. OBJECTIVE: To model the dosing of
milrinone in preterm infants for prevention of PLCS after surgical closure of
patent ductus arteriosus (PDA). METHODS: Milrinone time-concentration profiles
were simulated for 1,000 subjects using the volume of distribution and clearance
estimates based on one compartmental population pharmacokinetic model by
Paradisis et al. [Arch Dis Child Fetal Neonatal Ed 2007;92:F204-F209]. Dose
optimization was based on retrospectively collected demographic data from
neonates undergoing PDA ligation in Estonian PICUs between 2012 and 2014 and
existing pharmacodynamic data. The target plasma concentration was set at 150-200
ng/ml. RESULTS: The simulation study used demographic data from 31 neonates who
underwent PDA ligation. The median postnatal age was 13 days (range: 3-29) and
weight was 760 g (range: 500-2,351). With continuous infusion of milrinone 0.33
MUg/kg/min, the proportion of subjects within the desired concentration range was
0% by 3 h, 36% by 6 h, and 61% by 8 h; 99% of subjects exceeded the range by 18
h. The maximum proportion of total simulated concentrations in the target range
was attained with a bolus infusion of 0.73 MUg/kg/min for 3 h followed by a 0.16
MUg/kg/min maintenance infusion. CONCLUSION: Mathematical simulations suggest
that in preterm neonates the plasma time-concentration profile of milrinone can
be optimized with a slow loading dose followed by maintenance infusion.
PMID- 27490707
TI - All-Elastomer-Based Triboelectric Nanogenerator as a Keyboard Cover To Harvest
Typing Energy.
AB - The drastic expansion of consumer electronics (like personal computers, touch
pads, smart phones, etc.) creates many human-machine interfaces and multiple
types of interactions between human and electronics. Considering the high
frequency of such operations in our daily life, an extraordinary amount of
biomechanical energy from typing or pressing buttons is available. In this study,
we have demonstrated a highly flexible triboelectric nanogenerator (TENG) solely
made from elastomeric materials as a cover on a conventional keyboard to harvest
biomechanical energy from typing. A dual-mode working mechanism is established
with a high transferred charge density of ~140 MUC/m(2) due to both structural
and material innovations. We have also carried out fundamental investigations of
its performance dependence on various structural factors for optimizing the
electric output in practice. The fully packaged keyboard-shaped TENG is further
integrated with a horn-like polypyrrole-based supercapacitor as a self-powered
system. Typing in normal speed for 1 h, ~8 * 10(-4) J electricity could be
stored, which is capable of driving an electronic thermometer/hydrometer. Our
keyboard cover also performs outstanding long-term stability, water resistance,
as well as insensitivity to surface conditions, and the last feature makes it
useful to research the typing behaviors of different people.
PMID- 27490708
TI - alpha-Regioselective Barbier Reaction of Carbonyl Compounds and Allyl Halides
Mediated by Praseodymium.
AB - The first utility of praseodymium as a mediating metal in the Barbier reaction of
carbonyl compounds with allyl halides was reported in this paper. In contrast to
the traditional metal-mediated or catalyzed Barbier reactions, exclusive alpha
adducts were obtained in this one-pot reaction with a broad scope of substrates
and feasible reaction conditions.
PMID- 27490705
TI - Small Molecules in Development for the Treatment of Spinal Muscular Atrophy.
AB - Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease
resulting from pathologically low levels of survival motor neuron (SMN) protein.
The majority of mRNA from the SMN2 allele undergoes alternative splicing and
excludes critical codons, causing an SMN protein deficiency. While there is
currently no FDA-approved treatment for SMA, early therapeutic efforts have
focused on testing repurposed drugs such as phenylbutyrate (2), valproic acid
(3), riluzole (6), hydroxyurea (7), and albuterol (9), none of which has
demonstrated clinical effectiveness. More recently, clinical trials have focused
on novel small-molecule compounds identified from high-throughput screening and
medicinal chemistry optimization such as olesoxime (11), CK-2127107, RG7800,
LMI070, and RG3039 (17). In this paper, we review both repurposed drugs and small
molecule compounds discovered following medicinal chemistry optimization for the
potential treatment of SMA.
PMID- 27490709
TI - Chemoinformatics in the United Kingdom.
PMID- 27490710
TI - The Evolution of Digital Chemistry at Southampton.
AB - In this paper we take a historical view of e-Science and e-Research developments
within the Chemical Sciences at the University of Southampton, showing the
development of several stages of the evolving data ecosystem as Chemistry moves
into the digital age of the 21(st) Century. We cover our research on aspects of
the representation of chemical information in the context of the world wide web
(WWW) and its semantic enhancement (the Semantic Web) and illustrate this with
the example of the representation of quantities and units within the Semantic
Web. We explore the changing nature of laboratories as computing power becomes
increasing powerful and pervasive and specifically look at the function and role
of electronic or digital notebooks. Having focussed on the creation of chemical
data and information in context, we finish the paper by following the use and
reuse of this data as facilitated by the features provided by digital
repositories and their importance in facilitating the exchange of chemical
information touching on the issues of open and or intelligent access to the data.
PMID- 27490711
TI - Chemoinformatics at the University of Sheffield 2002-2014.
AB - This paper summarises work in chemoinformatics carried out in the Information
School of the University of Sheffield during the period 2002-2014. Research
studies are described on fingerprint-based similarity searching, data fusion,
applications of reduced graphs and pharmacophore mapping, and on the School's
teaching in chemoinformatics.
PMID- 27490712
TI - Designing Hydroxamates and Reversed Hydroxamates to Inhibit Zinc-containing
Proteases but not Cytochrome P450s: Insights from Quantum Mechanics and Protein
ligand Crystal Structures.
AB - The Hydroxamate is a useful functional group that binds to metals in a range of
enzymes, notably zinc in matrix metalloproteases and histone deacetylases. The
group is also able to form interactions with iron leading to inhibition of the
cytochromes P450, particularly the 3A4 isoform. We have studied the available
crystal structures of zinc-containing proteins bound to hydroxamates and compared
the observed geometries with those found by quantum mechanical calculations. This
has revealed the likely binding mode preferences for neutral and anionic
protonation states and highlighted the importance of electrostatic
complementarity. Calculations were also performed for the interaction of the
hydroxamate with iron in a heme environment, as found in the cytochromes P450.
These reveal that the preferred binding mode of hydroxamates in this environment
involves the s-trans conformation. These calculations provide design guidelines
for those interested in designing inhibitors of metalloenzymes that do not block
metabolism of other drugs. The ability to predict the geometries and energies of
binding modes that cannot be studied experimentally is an advantage offered by
this kind of study.
PMID- 27490713
TI - Greedy and Linear Ensembles of Machine Learning Methods Outperform Single
Approaches for QSPR Regression Problems.
AB - The application of Machine Learning to cheminformatics is a large and active
field of research, but there exist few papers which discuss whether ensembles of
different Machine Learning methods can improve upon the performance of their
component methodologies. Here we investigated a variety of methods, including
kernel-based, tree, linear, neural networks, and both greedy and linear ensemble
methods. These were all tested against a standardised methodology for regression
with data relevant to the pharmaceutical development process. This investigation
focused on QSPR problems within drug-like chemical space. We aimed to investigate
which methods perform best, and how the 'wisdom of crowds' principle can be
applied to ensemble predictors. It was found that no single method performs best
for all problems, but that a dynamic, well-structured ensemble predictor would
perform very well across the board, usually providing an improvement in
performance over the best single method. Its use of weighting factors allows the
greedy ensemble to acquire a bigger contribution from the better performing
models, and this helps the greedy ensemble generally to outperform the simpler
linear ensemble. Choice of data preprocessing methodology was found to be crucial
to performance of each method too.
PMID- 27490714
TI - Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine
response to a painful stimulus in combat veterans.
AB - OBJECTIVE: Although posttraumatic stress disorder (PTSD) and chronic pain
frequently occur in tandem, the pathophysiological mechanisms mediating this
comorbidity are poorly understood. Because excessive inflammation occurs in both
conditions, we examined the cerebrospinal fluid (CSF) concentrations of
inflammatory response mediators interleukin 1-beta (IL-1beta), interleukin 6 (IL
6), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNFalpha) and interleukin
10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat
veterans; 10 with PTSD and 11 combat controls (CC). METHODS: After completing
baseline quantitative sensory testing (QST) and psychological profiling, all
patients received an injection of capsaicin into the quadriceps muscle.
Spontaneously reported pain was measured for 30min after the capsaicin injection.
The evoked pain measure of temporal summation was tested between 70 and 110min
post capsaicin injection. Inflammatory (IL-1beta, IL-6, IL-8 TNFalpha) and anti
inflammatory (IL-10) CSF cytokines were measured before (baseline) and after
capsaicin injection over a time frame of 110min. RESULTS: Following intramuscular
capsaicin injection, pro-inflammatory cytokines [TNFalpha, IL-6, IL-8]
significantly increased (percent rise from baseline) in both groups, whereas IL
1beta significantly increased in the PTSD group only. The anti-inflammatory
cytokine IL-10 showed an immediate (within 10min) increase in the CC group;
however, the IL-10 increase in the PTSD group was delayed and not consistently
elevated until 70min post injection. CONCLUSION: These findings show significant
central nervous system (CNS) differences in the inflammatory response to a deep
pain stimulus in combat veterans with and without PTSD. They support the concept
that abnormally elevated neuroinflammatory response to pain stimuli may be one
CNS mechanism accounting for the high co-occurrence of PTSD and pain.
PMID- 27490715
TI - Chemoradiation for Locally Advanced Unresectable Pancreatic Cancer-What Now?
PMID- 27490716
TI - Non-insulated smooth motion, micro-needles RF fractional treatment for wrinkle
reduction and lifting of the lower face: International study.
AB - INTRODUCTION: Skin aging occurs through both intrinsic and extrinsic processes.
Fractional radiofrequency (RF) with a microneedling array is the newest form of
fractional therapy to be useful in treating aging skin. The current study
utilized a noninsulated fractional RF microneedling system. METHODS: This
multicenter clinical trial saw 49 patients complete 3 monthly treatments with the
new fractional RF microneedling treatments and be followed for 3 months following
their last treatment. Pain during treatment was recorded as well as overall
improvement using a GAIS scale. Adverse events were also noted. RESULTS: Forty
nine patients completed all of the treatments and follow-ups. Mild to moderate
erythema were reported immediately after treatment which lasted up to 12 hours
after the treatment. Pain, as measured on a 1-10 VAS, was noted to 4, on average.
The average Fitzpatrick's wrinkle scale score at baseline was 5.04 +/- 1.22, 1
month after 3 treatments 3.829 +/- 1.69 and 3 months after 3 treatments 3.5 +/-
1.66. These results are statistically highly significant (correlated T-test, P <
0.001). Improvement was shown in 100% of patients while 65% of patients had
significant improvement (GAIS levels 3-5). Significant skin tightening and skin
lifting were also observed. No unusual adverse events were noted throughout the
course of the study. CONCLUSION: This multicenter study showed significant
wrinkle reduction, skin tightening, and lifting of the mid and lower face with
the noninsulated fractional RF microneedling system. Lasers Surg. Med. 48:727
733, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490717
TI - Mechanisms of triple whammy acute kidney injury.
AB - Pre-renal acute kidney injury (AKI) results from glomerular haemodynamic
alterations leading to reduced glomerular filtration rate (GFR) with no
parenchymal compromise. Renin-angiotensin system inhibitors, such as angiotensin
converting enzyme inhibitors (ACEIs), angiotensin receptor antagonists (ARAs),
non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics, are highly
prescribed drugs that are frequently administered together. Double and triple
associations have been correlated with increased pre-renal AKI incidence, termed
"double whammy" and "triple whammy", respectively. This article presents an
integrative analysis of the complex interplay among the effects of NSAIDs,
ACEIs/ARAs and diuretics, acting alone and together in double and triple
therapies. In addition, we explore how these drug combinations alter the
equilibrium of regulatory mechanisms controlling blood pressure (renal perfusion
pressure) and GFR to increase the odds of inducing AKI through the concomitant
reduction of blood pressure and distortion of renal autoregulation. Using this
knowledge, we propose a more general model of pre-renal AKI based on a multi
whammy model, whereby several factors are necessary to effectively reduce net
filtration. The triple whammy was the only model associated with pre-renal AKI
accompanied by a course of other risk factors, among numerous potential
combinations of clinical circumstances causing hypoperfusion in which renal
autoregulation is not operative or is deregulated. These factors would uncouple
the normal BP-GFR relationship, where lower GFR values are obtained at every BP
value.
PMID- 27490718
TI - Macular Ganglion Cell Imaging Study: Covariate Effects on the Spectral Domain
Optical Coherence Tomography for Glaucoma Diagnosis.
AB - PURPOSE: To evaluate the effect of multiple covariates on the diagnostic
performance of the Cirrus high-definition optical coherence tomography (HD-OCT)
for glaucoma detection. METHODS: A prospective case-control study was performed
and included 173 recently diagnosed glaucoma patients and 63 unaffected
individuals from the Macular Ganglion Cell Imaging Study. Regression analysis of
receiver operating characteristic were conducted to evaluate the influence of
age, spherical equivalent, axial length, optic disc size, and visual field index
on the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary
retinal nerve fiber layer (RNFL) measurements. RESULTS: Disease severity, as
measured by visual field index, had a significant effect on the diagnostic
performance of all Cirrus HD-OCT parameters. Age, axial length and optic disc
size were significantly associated with diagnostic accuracy of average
peripapillary RNFL thickness, whereas axial length had a significant effect on
the diagnostic accuracy of average GCIPL thickness. CONCLUSIONS: Diagnostic
performance of the Cirrus HD-OCT may be more accurate in the advanced stages of
glaucoma than at earlier stages. A smaller optic disc size was significantly
associated with improved the diagnostic ability of average RNFL thickness
measurements; however, GCIPL thickness may be less affected by age and optic disc
size.
PMID- 27490720
TI - Associations of various perceived-stress situations with depressive symptoms in
>=50-year old Taiwanese men and women: Results from the Taiwan Longitudinal Study
on Aging.
AB - This study was aimed to evaluate the cross-sectional and longitudinal
associations between various perceived-stress and depressive symptoms in old
Taiwanese men and women aged 50 years and over. Data were derived from the Taiwan
Longitudinal Study on Aging. Stress for health, finance, and family members'
related issues were all cross-sectionally associated with concurrent depressive
symptoms for men and women (all P<0.05). Increased/constant-high health stress
was positively associated with subsequent depressive symptoms in both genders
(all P<0.05). Constantly high job stress and increased stress over family
members' problems were associated with higher likelihood of subsequent depressive
symptoms in men (P<0.05). Constantly high/increased financial stress and
relationship strain with family members were positively associated with
subsequent depressive symptoms in women (all P<0.05). The results suggest that
stress for health, job, finance, and family members-related issues are unequally
associated with depressive symptoms among Taiwanese men and women aged 50 years
and over. Changes of health stress even reduced are significantly associated with
subsequent depressive symptoms. Long-term job stress and increased stress over
family members' problems increase occurrences of men's depressive symptoms, while
increased/long-term financial stress and relationship-strain with family members
increase occurrences of women's depressive symptoms. Long-term high health stress
has more impacts on men's depressive symptoms than women's, while long-term high
relationship strain with family members has more impacts on women's depressive
symptoms than men's.
PMID- 27490722
TI - Tailoring Graphene Nanosheets for Highly Improved Dispersion Stability and
Quantitative Assessment in Nonaqueous Solvent.
AB - Aggregation is a critical limitation for the practical application of graphene
based materials. Herein, we report that graphene oxide (GO) nanosheets chemically
modified with ethanolamine (EA), ethylene glycol (EG), and sulfanilic acid (SA)
demonstrate superior dispersion stability in organic solvents, specifically EG,
based on the differences in their covalent chemistries. Functionalized GO was
successfully dispersed in EG at a concentration of 9.0 mg mL(-1) (0.50 vol %),
the highest dispersion concentration reported to date. Moreover, our study
introduces a unique analytical method for the assessment of dispersion stability
and successfully quantifies the instability index based on transmission profiles
under centrifugation cycles. Interestingly, GO-EG and GO-EA exhibited highly
improved dispersion stabilities approximately 96 and 48 times greater than that
of GO in EG solvent, respectively. This finding highlights the critical role of
surface functional groups in the enhancement of chemical affinity and miscibility
in the surrounding media. We anticipate that the novel structural designs and
unique tools presented in this study will further the understanding and
application of chemically functionalized carbon materials.
PMID- 27490721
TI - Antiviral activity of Thiosemicarbazones derived from alpha-amino acids against
Dengue virus.
AB - The endemicity and seasonal outbreaks of Dengue disease in most tropical and
subtropical countries underscores an urgent need to develop effective prevention
and control measures. Development of a Dengue vaccine, which is complicated by
the Antibody Dependent Enhancement effect (ADE), a viral inhibitor, seems prudent
as it would inhibit the spread of the virus. In vitro methods such as MTT assay
and plaque formation unit reduction assays were employed for screening the viral
inhibitory property of alpha-amino acid based Thiosemicarbazides. The results
elicits that at concentrations not exceeding the maximum non cytotoxic
concentration (MNCC), these compounds completely prevented Dengue virus infection
in vero cells as indicated by the absence of cytopathic effects in a dose
dependent manner. The high potency of Bz-Trp-TSC against all four types of Dengue
virus infection elevates Thiosemicarbazide as a lead antiviral agent for Dengue
disease. Screening small molecules for antiviral activity against the most
rapidly spreading mosquito-borne viral disease is being explored by several
research groups. Our findings would help to augment the efforts to identify the
lead compounds for antiviral therapy to combat the Dengue disease. J. Med. Virol.
89:546-552, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490723
TI - Subacute Myopericarditis Without Myocardial Infarction Treated With Intravenous
Immunoglobulin in a Child With Marked Elevation of Plasma Cardiac Troponin I.
PMID- 27490719
TI - Literature-Informed Analysis of a Genome-Wide Association Study of Gestational
Age in Norwegian Women and Children Suggests Involvement of Inflammatory
Pathways.
AB - BACKGROUND: Five-to-eighteen percent of pregnancies worldwide end in preterm
birth, which is the major cause of neonatal death and morbidity. Approximately
30% of the variation in gestational age at birth can be attributed to genetic
factors. Genome-wide association studies (GWAS) have not shown robust evidence of
association with genomic loci yet. METHODS: We separately investigated 1921
Norwegian mothers and 1199 children from pregnancies with spontaneous onset of
delivery. Individuals were further divided based on the onset of delivery:
initiated by labor or prelabor rupture of membranes. Genetic association with
ultrasound-dated gestational age was evaluated using three genetic models and
adaptive permutations. The top-ranked loci were tested for enrichment in 12
candidate gene-sets generated by text-mining PubMed abstracts containing
pregnancy-related keywords. RESULTS: The six GWAS did not reveal significant
associations, with the most extreme empirical p = 5.1 * 10-7. The top loci from
maternal GWAS with deliveries initiated by labor showed significant enrichment in
10 PubMed gene-sets, e.g., p = 0.001 and 0.005 for keywords "uterus" and
"preterm" respectively. Enrichment signals were mainly caused by
infection/inflammation-related genes TLR4, NFKB1, ABCA1, MMP9. Literature
informed analysis of top loci revealed further immunity genes: IL1A, IL1B, CAMP,
TREM1, TFRC, NFKBIA, MEFV, IRF8, WNT5A. CONCLUSION: Our analyses support the role
of inflammatory pathways in determining pregnancy duration and provide a list of
32 candidate genes for a follow-up work. We observed that the top regions from
GWAS in mothers with labor-initiated deliveries significantly more often overlap
with pregnancy-related genes than would be expected by chance, suggesting that
increased sample size would benefit similar studies.
PMID- 27490725
TI - Impact of Chest Radiography on Antibiotic Treatment for Children With Suspected
Pneumonia.
AB - OBJECTIVE: National guidelines discourage routine chest radiographs (CXRs) to
confirm suspected pneumonia in children managed as outpatients. However, limiting
CXRs may lead to antibiotic overuse. We examined the impact of CXRs and clinical
suspicion on antibiotic treatment for children with suspected pneumonia. METHODS:
Children aged 3 months to 18 years undergoing CXR for suspected pneumonia in a
pediatric emergency department were prospectively enrolled. Before CXR,
physicians indicated their initial plan for antibiotics (yes or no) and clinical
suspicion for radiographic pneumonia (<5%, 5-10%, 11-20%, 21-50%, 51-75%, >75%).
Subjects had radiographic pneumonia if their CXRs demonstrated definite or
possible findings of pneumonia. We compared antibiotic treatment according to pre
CXR antibiotic plan and suspicion for pneumonia and CXR results. RESULTS: Among
the 107 children with a plan for antibiotics before CXR, 72% ultimately received
antibiotics compared with 19% of the 1503 children without a pre-CXR plan for
antibiotics (P < 0.001). Among those patients with a pre-CXR plan for
antibiotics, 96% of children with radiographic pneumonia were ultimately treated
compared with 54% without radiographic pneumonia (P < 0.001). If antibiotics were
not initially planned, 37% with radiographic pneumonia were treated compared with
8% without radiographic pneumonia (P < 0.001). The use of CXR was more likely to
influence antibiotic prescribing patterns when the clinical suspicion of
pneumonia was low (<20%). CONCLUSIONS: Among children with high suspicion for
pneumonia, CXRs infrequently altered the initial plan for antibiotics. However,
when clinical suspicion for pneumonia was low, the use of CXR may reduce
unnecessary antibiotic use.
PMID- 27490724
TI - Evaluation of Anaphylaxis Management in a Pediatric Emergency Department.
AB - OBJECTIVE: In 2006, the National Institute of Allergy and Infectious Disease
established evidence-based treatment guidelines for anaphylaxis. The purpose of
our study was to evaluate provider adherence to guidelines-based management for
anaphylaxis in a tertiary care pediatric emergency department (ED). METHODS:
Retrospective chart review was conducted of patients (0-18 years) presenting to
the Arkansas Children Hospital ED from 2004 to 2011 for the treatment of
anaphylaxis using International Classification of Diseases, Ninth Edition, codes.
Multiple characteristics including demographics, clinical features, allergen
source, and anaphylaxis management were collected. Fisher exact or chi tests were
used to compare proportion of patients treated with intramuscular (IM)
epinephrine in the preguideline versus postguideline period. Relative risk (RR)
statistics were computed to estimate the ratio of patients who received self
injectable epinephrine prescription and allergy follow-up in the preguideline and
postguideline groups. RESULTS: A total of 187 patients (median [range] age, 7 [1
18] years; 67% male; 48% African American) were evaluated. Food (44%) and
hymenoptera stings (22%) were commonly described culprit allergens, whereas 29%
had no identifiable allergen. Only 47% (n = 87) received epinephrine in the ED
and 31% (n = 27) via the preferred IM route. Comparing postguideline (n = 126)
versus preguideline (n = 61) periods demonstrated increase in the usage of the IM
route (46% postguideline vs 6% preguideline; risk ratio (RR), 7.64; 95%
confidence interval [CI], 2.04-46.0; P < 0.001). Overall, 61% (n = 115) of the
patients received self-injectable epinephrine upon discharge, and there were no
significant differences between the groups (64% postguideline vs 56%
preguideline, P = 0.30). Postguideline patients were more likely to receive a
prescription compared with preguideline patients (64% postguideline vs 56%
preguideline; RR, 1.15; 95% CI, 0.89-1.55; P = 0.30). Only 45% (n = 85) received
an allergy referral. Postguideline patients were more likely to receive an
allergy referral than preguideline patients (48% postguideline vs 41%
preguideline; RR, 1.16; 95% CI, 0.81-1.73; P = 0.40). CONCLUSIONS: Provider use
of IM epinephrine has improved since anaphylaxis guidelines were published.
However, more provider education is needed to improve overall adherence of
guidelines in a tertiary care pediatric ED.
PMID- 27490726
TI - A Misdirected Patient Transfer Raises Emergency Medical Treatment and Labor Act
Liability Issues.
AB - Children often require transfer to pediatric hospital emergency departments (EDs)
after evaluation in community hospital EDs. Such transfers are regulated by the
federal Emergency Medical Treatment and Labor Act. Unusual circumstances, such as
logistical errors in the physical transfer of the patient, may increase Emergency
Medical Treatment and Labor Act-related liability risks for hospitals and ED
physicians.
PMID- 27490727
TI - Deep Vein Thrombus Occurring Immediately After Blunt Abdominal Trauma.
AB - CASE: A 13-year-old adolescent girl with blunt abdominal injury was transferred
to our hospital. Enhanced computed tomography (CT) showed not only
retroperitoneal hematoma around the inferior vena cava and left common iliac vein
but also thrombus extending from the left common iliac vein to the femoral vein.
OUTCOME: Enhanced CT performed on the second day revealed no increase in
retroperitoneal hematoma and a new small thrombus in the popliteal vein.
Anticoagulant therapy was therefore started with administration of unfractionated
heparin. Administration of warfarin was started on the 12th day and heparin
administration was stopped on the 14th day. The patient was discharged on the
19th day with continuation of warfarin administration. Enhanced CT performed 10
months after injury showed no thrombus, and the administration of warfarin was
then stopped. CONCLUSIONS: She was successfully treated with the appropriate
start time and control of anticoagulation therapy based on careful evaluation of
her general condition.
PMID- 27490728
TI - Accidental Burn by Intentional Laxative Use.
AB - OBJECTIVE: The purpose of this study was to present a case report and review the
relevant literature on laxative-induced dermatitis being mistaken for scald
injury and child abuse. CASE: A 33-month-old girl presented with partial
thickness burn to the buttocks and perineum, which were suspected to be caused by
child abuse. On further investigation, the parents had been administering large
doses of laxatives to the child for chronic constipation. DISCUSSION: Child abuse
by burning has characteristic physical examination findings, which differ from
the pattern of laxative-induced dermatitis that has been reported in the
literature. Diapers appear to be a risk factor for laxative-induced dermatitis.
Surprisingly, the dose of laxative does not correlate with the severity of the
burn injury. All physicians must be aware of the possibility of laxative-induced
dermatitis mimicking scald burn injury to the buttocks. Parents should be
educated about the risk of administering over-the-counter laxatives to children.
PMID- 27490729
TI - Point-of-Care Ultrasound to Assess Anuria in Children.
AB - Anuria in children may arise from a host of causes and is a frequent concern in
the emergency department. This review focuses on differentiating common causes of
obstructive and nonobstructive anuria and the role of point-of-care ultrasound in
this evaluation. We discuss some indications and basic techniques for bedside
ultrasound imaging of the urinary system.
PMID- 27490730
TI - Point-of-Care Ultrasound to Assess Anuria in Children.
PMID- 27490731
TI - Essentials of Pediatric Emergency Medicine Fellowship: Part 4: Beyond Clinical
Education.
AB - This article is the third in a 7-part series that aims to comprehensively
describe the current state and future directions of pediatric emergency medicine
fellowship training from the essential requirements to considerations for
successfully administering and managing a program to the careers that may be
anticipated upon program completion. This article focuses on the skills beyond
clinical training required of pediatric emergency medicine physicians including
teaching, leadership, teamwork, and communication.
PMID- 27490732
TI - Emergency Department Point-of-Care Hip Ultrasound and Its Role in the Diagnosis
of Septic Hip Arthritis: A Case Report.
AB - We present a case of an 11-year-old girl with eye swelling and hip pain and the
use of point-of-care hip ultrasound (US) to facilitate diagnosis of a septic hip.
We review the US technique, sonographic findings, and relevant literature
regarding point-of-care hip US.
PMID- 27490733
TI - Diagnosis of Cystic Teratoma Facilitated by Point-of-Care Ultrasonography.
AB - Abdominal pain and constipation are common chief complaints in the pediatric
emergency department. We present a case of a child with pain, abdominal
distention, and constipation ultimately diagnosed with an ovarian teratoma and
the role of point-of-care ultrasonography in the evaluation.
PMID- 27490734
TI - Pediatric Emergency Medicine: Legal Briefs.
PMID- 27490735
TI - PEMNetwork: Barriers and Enablers to Collaboration and Multimedia Education in
the Digital Age.
AB - In January 2005, PEMFellows.com was created to unify fellows in pediatric
emergency medicine. Since then, the website has expanded, contracted, and focused
to adapt to the interests of the pediatric emergency medicine practitioner during
the internet boom. This review details the innovation of the PEMNetwork, from the
inception of the initial website and its evolution into a needs-based, user
directed educational hub. Barriers and enablers to success are detailed with
unique examples from descriptive analysis and metrics of PEMNetwork web traffic
as well as examples from other online medical communities and digital education
websites.
PMID- 27490736
TI - Pediatric Emergency Department Return: A Literature Review of Risk Factors and
Interventions.
AB - BACKGROUND AND OBJECTIVE: Children discharged from emergency departments (EDs)
are often at risk for ED return. The objective was to identify risk factors and
interventions to mitigate or prevent ED return among this patient population.
METHODS: Structured literature review of PubMed and clinicaltrials.gov was
conducted to identify relevant studies. Inclusion criteria were studies
evaluating ED returns by identifying risk factors and interventions in the
pediatric population. Emergency department return was defined as returning to the
ED within 1 year after initial visit. Abstract and full text articles were
reviewed, and data were abstracted by 2 independent authors. RESULTS: A total of
963 articles were screened and yielded 42 potential relevant articles involving
pediatric population. After full text review, a total of 12 articles were
included in the final analysis (6 on risk factors and 6 on interventions). Risk
factors for pediatric ED return included behavioral/psychiatric problems, younger
age, acuity of illness, medical history of asthma, and social factors.
Interventions included computer-generated instructions, postdischarge telephone
coaching, ED-made appointments, case management, and home environment
intervention. Emergency department-made appointments and postdischarge telephone
coaching plus monetary incentive improved outpatient follow-up rate but not ED
return. Home environment assessment coupled with case management reduced ED
returns specifically among asthma patients. CONCLUSIONS: Several patient and
visit characteristics can help predict children at risk for ED return. Although
some interventions are successful at improving postdischarge follow-up, most did
not reduce ED returns.
PMID- 27490737
TI - ECGs in the ED.
PMID- 27490738
TI - Precipitant induced porosity augmentation of polystyrene preserves the
chondrogenicity of human chondrocytes.
AB - Cells constantly sense and receive chemical and physical signals from neighboring
cells, interstitial fluid, and extracellular matrix, which they integrate and
translate into intracellular responses. Thus, the nature of the surface on which
cells are cultured in vitro plays an important role for cell adhesion,
proliferation, and differentiation. Autologs chondrocyte implantation is
considered the treatment of choice for larger cartilage defects in the knee. To
obtain a sufficient number of chondrocytes for implantation multiple passaging is
often needed, which raises concerns about the changes in the chondrogenic
phenotype. In the present study, we analyzed the effect at cellular and molecular
level of precipitant induced porosity augmentation (PIPA) of polystyrene surfaces
on proliferation and differentiation of human chondrocytes. Human chondrocytes
were isolated from healthy patients undergoing anterior cruciate ligament
reconstruction and cultured on PIPA modified polystyrene surfaces. Microscopical
analysis revealed topographically arranged porosity with micron pores and
nanometer pits. Chondrocytes cultured on PIPA surfaces revealed no difference in
cell viability and proliferation, but gene- and protein expressions of collagen
type II were pronounced in the first passage of chondrocytes when compared to
chondrocytes cultured on control surfaces. Additionally, an analysis of 40
kinases revealed that chondrocytes expanded on PIPA caused upregulated PI3K/mTOR
pathway activation and inhibition of mTORC1 resulted in reduced sGAG synthesis.
These findings indicate that PIPA modified polystyrene preserved the
chondrogenicity of expanded human chondrocytes at gene and protein levels, which
clinically may be attractive for the next generation of cell-culture surfaces for
ex vivo cell growth. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
104A: 3073-3081, 2016.
PMID- 27490739
TI - Does quality of developmental care in NICUs affect health-related quality of life
in 5-y-old children born preterm?
AB - BACKGROUND: Preterm birth and Neonatal Intensive Care Unit (NICU) stay are early
adverse experiences, which may affect health-related quality of life (HRQoL) even
in the absence of prematurity-related morbidities. The aim of this multicenter
longitudinal study was to examine the relation between quality levels of NICU
Developmental Care (DC) and HRQoL at 60 mo in children who were born preterm.
METHODS: HRQoL of 102 very preterm (VPT) children from 20 NICUs and 110 full-term
controls was assessed using TNO-AZL Preschool Children's Quality of Life
Questionnaire (TAPQOL). In VPT children, we compared HRQoL by splitting NICUs
into units with high- and low-quality of DC according to the following two
factors: (i) the infant centered care (ICC), and (ii) the infant pain management
(IPM). RESULTS: Compared to VPT children from NICUs with high-quality of ICC, VPT
children from NICUs with low-quality in ICC scored lower in HRQoL component which
resulted from the aggregation of lively, positive emotionality, social and motor
functioning. No differences were found between VPT children from high-quality ICC
NICUs and full-term children and for the IPM index. CONCLUSION: Findings suggest
that higher quality of DC in NICU related to ICC might mitigate long-term
negative quality of life outcomes.
PMID- 27490743
TI - Medicolegal-Malpractice and Ethical Issues in Radiology.
PMID- 27490742
TI - A validated protocol to quantify severity of male urogenital feminization using
the MOUSE (Mouse objective urethral severity evaluation).
AB - BACKGROUND: Congenital abnormalities vary in presentation, yet studies using
model organisms tend to focus on occurrence rather than severity of the defect.
Scoring severity of abnormalities in model systems allows explicit hypothesis
testing during basic, translational, and reverse translational studies. We
developed and validated a protocol to quantify severity of male urogenital
feminization (hypospadias) in the mouse model. Hypospadias is one of the most
common birth defects in the world. METHODS: To induce genital feminization,
pregnant mice were exposed to different concentrations of the antiandrogen
vinclozolin. Genitalia were photographed at gestational age 18.5. A dichotomous
scoring system to evaluate genital feminization was developed, and validated
against histological measurements of urethral length. A training protocol was
developed for novice scorers, and criteria were defined to evaluate precision and
accuracy of scores. RESULTS: Vinclozolin induced variation in hypospadias
severity. Severity scores were tightly correlated with histologically determined
urethral length and both techniques showed similar dose-response relationships.
Novice observers were trained to precisely and accurately score hypospadias
severity. CONCLUSION: This standardized scoring system advances the mouse as a
model to study urogenital development, and will facilitate research on the
mechanisms driving genital feminization in males, and aid translational
hypospadias research.
PMID- 27490744
TI - Open and Arthroscopic Anterior Shoulder Stabilization.
PMID- 27490741
TI - Gestational diabetes is associated with changes in placental microbiota and
microbiome.
AB - BACKGROUND: The human microbiota is a modulator of the immune system. Variations
in the placental microbiota could be related with pregnancy disorders. We
profiled the placental microbiota and microbiome in women with gestational
diabetes (GDM) and studied its relation to maternal metabolism and placental
expression of anti-inflammatory cytokines. METHODS: Placental microbiota and
microbiome and expression of anti-inflammatory cytokines (IL10, TIMP3, ITGAX, and
MRC1MR) were analyzed in placentas from women with GDM and from control women.
Fasting insulin, glucose, O'Sullivan glucose, lipids, and blood cell counts were
assessed at second and third trimester of pregnancy. RESULTS: Bacteria belonging
to the Pseudomonadales order and Acinetobacter genus showed lower relative
abundance in women with GDM compared to control (P < 0.05). In GDM, lower
abundance of placental Acinetobacter associated with a more adverse metabolic
(higher O'Sullivan glucose) and inflammatory phenotype (lower blood eosinophil
count and lower placental expression of IL10 and TIMP3) (P < 0.05 to P = 0.001).
Calcium signaling pathway was increased in GDM placental microbiome. CONCLUSION:
A distinct microbiota profile and microbiome is present in GDM. Acinetobacter has
been recently shown to induce IL-10 in mice. GDM could constitute a state of
placental microbiota-driven altered immunologic tolerance, making placental
microbiota a new target for therapy in GDM.
PMID- 27490740
TI - Inotropes do not increase cardiac output or cerebral blood flow in preterm
piglets.
AB - BACKGROUND: The preterm newborn is at high risk of developing cardiovascular
compromise during the first day of life and this is associated with increased
risk of brain injury. Standard treatments are volume expansion and administration
of inotropes, typically dopamine and/or dobutamine, but there is limited evidence
that inotropes improve clinical outcomes. This study investigated the efficacy of
dopamine and dobutamine for the treatment of cardiovascular compromise in the
preterm newborn using a piglet model. METHODS: Preterm and term piglets were
assigned to either dopamine, dobutamine or control infusions. Heart rate, left
ventricular contractility, cardiac output, blood pressure, and cerebral and
regional blood flows were measured during baseline, low (10 ug/kg/h), and high
(20 ug/kg/h) dose infusions. RESULTS: At baseline, preterm piglets had lower
cardiac contractility, cardiac output, blood pressure, and cerebral blood flow
compared to term piglets. The response of preterm piglets to either dopamine or
dobutamine administration was less than in term piglets. In both preterm and term
piglets, cardiac output and cerebral blood flow were unaltered by either
inotrope. CONCLUSION: In order to provide better cardiovascular support, it may
be necessary to develop treatments that target receptors with a more mature
profile than adrenoceptors in the preterm newborn.
PMID- 27490745
TI - Risks and Benefits of Simultaneous Bilateral Total Knee Arthroplasty: A Critical
Analysis Review.
PMID- 27490746
TI - Open Tibial Fractures: Updated Guidelines for Management.
PMID- 27490747
TI - Imaging Criteria for the Quantification of Disc Degeneration: A Systematic
Review.
PMID- 27490748
TI - Balancing C=C Functionalization and C=O Reduction in Cu-H Catalysis.
AB - Coppercabana: The copper(I) hydride catalyzed functionalization of unactivated
alkenes has been shown to be compatible with conventional carbonyl reduction.
Through the combination of both pathways or complete suppression of C=O reduction
in favor of C=C functionalization, methods for the stereoselective synthesis of a
variety of chiral molecules have been developed.
PMID- 27490749
TI - Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma.
AB - According to the American skin cancer foundation, there are more new cases of
skin cancer than the combined incidence of cancers of the breast, prostate, lung,
and colon each year, and malignant melanoma represents its deadliest form. About
50% of all cases are characterized by a particular mutation BRAF(V600E) in the
BRAF (Rapid Acceleration of Fibrosarcoma gene B) gene. Recently developed highly
specific drugs are able to fight BRAF(V600E) mutated tumors but require
diagnostic tools for fast and reliable mutation detection to warrant treatment
efficiency. We completed a preliminary clinical trial applying cantilever array
sensors to demonstrate identification of a BRAF(V600E) single-point mutation
using total RNA obtained from biopsies of metastatic melanoma of diverse sources
(surgical material either frozen or fixated with formalin and embedded in
paraffin). The method is faster than the standard Sanger or pyrosequencing
methods and comparably sensitive as next-generation sequencing. Processing time
from biopsy to diagnosis is below 1 day and does not require PCR amplification,
sequencing, and labels.
PMID- 27490750
TI - Thermodynamic Stability and Defect Chemistry of Bismuth-Based Lead-Free Double
Perovskites.
AB - Bismuth- or antimony-based lead-free double perovskites represented by Cs2
AgBiBr6 have recently been considered promising alternatives to the emerging lead
based perovskites for solar cell applications. These new perovskites belong to
the Fm3? m space group and consist of two types of octahedra alternating in a
rock-salt face-centered cubic structure. We show, by density functional theory
calculations, that the stable chemical potential region for pure Cs2 AgBiBr6 is
narrow. Ag vacancies are a shallow accepters and can easily form, leading to
intrinsic p-type conductivity. Bi vacancies and AgBi antisites are deep acceptors
and should be the dominant defects under the Br-rich growth conditions. Our
results suggest that the growth of Cs2 AgBiBr6 under Br-poor/Bi-rich conditions
is preferred for suppressing the formation of the deep defects, which is
beneficial for maximizing the photovoltaic performance.
PMID- 27490751
TI - Focal segmental glomerulosclerosis in pediatric kidney transplantation: 30 years'
experience.
AB - : From 1982 to 2011, 53 kidney transplantations (KT) for pediatric focal
segmental glomerulosclerosis (FSGS) were recorded in the National Israeli Kidney
Transplant Registry (NIKTR): 22-primary (1?) FSGS, 25-proved/suspected genetic
secondary (2?) FSGS, six lost/incomplete files/other. Half (56%) of 23 patients
with 2? FSGS were Israeli-Arabs vs 29% of 1? FSGS KT recipients. 1? FSGS
recurrence occurred in 64% (14/22) of 22 KT in 17 patients aged (median) 14 years
vs 1/25 of 2? FSGS (P<.001). Early graft days/nonfunction occurred in 9/14 (64%),
2/8 (25%) and 2/25 (4%) of recurrent 1? FSGS (rFSGS), nonr1? FSGS and 2? FSGS,
respectively. Twelve biopsies performed in nine of these grafts at (median) 8
days (range 5-60 days) post-KT showed: ATN-5, suspected rejection-4, rFSGS-2,
normal kidney-1; rFSGS was diagnosed eventually in 8/9. Dialysis need during the
first month post-KT was significantly associated with FSGS recurrence: 6/14 (43%)
for rFSGS vs 2/8 (25%) for non-rFSGS. Plasmapheresis (PP) achieved complete and
partial rFSGS remission in 5/9 and 2/9 grafts, respectively. Three grafts were
excised during the first 60 days post-KT for: nonfunction (1) and bleeding (2).
Remaining grafts' GFR was: 78, 42, and 91 mL/min (median) at 5.3, 4.75, and 8
years follow-up for non-rFSGS, rFSGS, and 2? FSGS grafts, respectively.
CONCLUSIONS: Early PP implementation should be considered after KT for 1? FSGS
patients with early graft dysfunction despite delayed proteinuria and nonspecific
biopsy.
PMID- 27490753
TI - The Use of Augment Devices in Revision Acetabular Surgery.
PMID- 27490754
TI - Wrong-Level Spine Surgery.
PMID- 27490752
TI - Bilateral tDCS on Primary Motor Cortex: Effects on Fast Arm Reaching Tasks.
AB - BACKGROUND: The effects produced by transcranial direct current stimulation
(tDCS) applied to the motor system have been widely studied in the past, chiefly
focused on primary motor cortex (M1) excitability. However, the effects on
functional tasks are less well documented. OBJECTIVE: This study aims to evaluate
the effect of tDCS-M1 on goal-oriented actions (i.e., arm-reaching movements;
ARM), in a reaction-time protocol. METHODS: 13 healthy subjects executed dominant
ARM as fast as possible to one of two targets in front of them while surface EMG
was recorded. Participants performed three different sessions. In each session
they first executed ARM (Pre), then received tDCS, and finally executed Post,
similar to Pre. Subjects received three different types of tDCS, one per session:
In one session the anode was on right-M1 (AR), and the cathode on the left-M1
(CL), thus termed AR-CL; AL-CR reversed the montage; and Sham session was applied
likewise. Real stimulation was 1mA-10min while subjects at rest. Three different
variables and their coefficients of variation (CV) were analyzed: Premotor times
(PMT), reaction-times (RT) and movement-times (MT). RESULTS: triceps-PMT were
significantly increased at Post-Sham, suggesting fatigue. Results obtained with
real tDCS were not different depending on the montage used, in both cases PMT
were significantly reduced in all recorded muscles. RT and MT did not change for
real or sham stimulation. RT-CV and PMT-CV were reduced after all stimulation
protocols. CONCLUSION: tDCS reduces premotor time and fatigability during the
execution of fast motor tasks. Possible underlying mechanisms are discussed.
PMID- 27490755
TI - Congenital Clubfoot.
PMID- 27490756
TI - Shared Decision Making in Total Joint Replacement.
PMID- 27490758
TI - Quantification of Estrogen Receptor Expression in Normal Breast Tissue in
Postmenopausal Women With Breast Cancer and Association With Tumor Subtypes.
AB - Estrogen exposure is important in the pathogenesis of breast cancer and is a
contributing risk factor. In this study we quantified estrogen receptor (ER)
alpha expression in normal breast epithelium (NBR) in women with breast cancer
and correlated it with breast cancer subtypes. Tissue microarrays were
constructed from 204 breast cancer patients for whom normal breast tissue away
from tumor was available. Slides stained with ER were scanned and expression in
normal terminal duct lobular epithelium was quantitated using computer-assisted
image analysis. ER expression in normal terminal duct lobular epithelium of
postmenopausal women with breast cancer was significantly associated with
estrogen and triple (estrogen, progesterone receptors, and HER2) negative
phenotypes. Also increased age at diagnosis was significantly associated with ER
expression in NBR. ER positivity in normal epithelium did not vary by tumor size,
lymph node status, tumor grade, or stage. On the basis of quantitative image
analysis, we confirm that ER expression in NBR increases with age in women with
breast cancer, and report for the first time, a significant association between
ER expression in NBR with ER-negative and triple-negative cancers in
postmenopausal women.
PMID- 27490757
TI - Manufacturing Man-Made Magnetosomes: High-Throughput In Situ Synthesis of
Biomimetic Magnetite Loaded Nanovesicles.
AB - A new synthetic method for the production of artificial magnetosomes, i.e., lipid
coated vesicles containing magnetic nanoparticles, is demonstrated. Magnetosomes
have considerable potential in biomedical and other nanotechnological
applications but current production methods rely upon magnetotactic bacteria
which limits the range of sizes and shapes that can be generated as well as the
obtainable yield. Here, electrohydrodynamic atomization is utilized to form
nanoscale liposomes of tunable size followed by electroporation to transport iron
into the nanoliposome core resulting in magnetite crystallization. Using a
combination of electron and fluorescence microscopy, dynamic light scattering,
Raman spectroscopy, and magnetic susceptibility measurements, it is shown that
single crystals of single-phase magnetite can be precipitated within each
liposome, forming a near-monodisperse population of magnetic nanoparticles. For
the specific conditions used in this study the mean particle size is 58 nm (+/-8
nm) but the system offers a high degree of flexibility in terms of both the size
and composition of the final product.
PMID- 27490759
TI - Parafibromin, APC, and MIB-1 Are Useful Markers for Distinguishing Parathyroid
Carcinomas From Adenomas.
AB - BACKGROUND: Differentiation of parathyroid carcinoma (PC) from parathyroid
adenoma (PA) relies solely on the pathologic determination of invasion of
surrounding structures and/or distant metastasis. Parathyroid lesions with
atypical histologic features with no demonstration of invasion or metastasis
present a diagnostic dilemma. Different authors report a parafibromin and
adenomatous polyposis coli (APC) loss or reduction in PC cases. High
proliferative activity of MIB-1 and increased galectin 3 expression are reported
in PC. There is no clear cutoff for the sensitivity, specificity, or predictive
value for all these markers. METHODS: The immunohistochemical expression of
parafibromin, APC, MIB-1, and galectin 3 was studied in 73 adenomas, 21 PCs, and
3 atypical adenomas. The presence or absence of each marker was identified
through the use of a comprehensive scoring system based on multiplying the
percentage of tumor cells stained (0 to 100) and the staining intensity (0 to 3)
on each biopsy. The highest score that any slide could reach was 300. A cutoff of
>100 was used to consider the specimen positive for parafibromin, APC, or
galectin 3 staining. MIB-1 proliferation indices were calculated using image
cytometry; proliferation indices >5% were considered positive. RESULTS: We
identified parafibromin loss in 7/21 (33%) carcinomas and 1/73 (1%) adenomas.
Loss of APC was seen in 20/21 (95%) carcinomas and 38/73 (52%) adenomas. MIB-1
indices were elevated in 18/21 (86%) carcinomas. MIB-1 indices were <5% in all
(100%) adenomas. MIB-1 indices were elevated in 2/3 (67%) atypical adenomas.
CONCLUSIONS: Our study presents a clear cutoff to determine the practicality of
using parafibromin, APC, and MIB-1 as immunohistochemical markers to
differentiate between PCs and PAs. Loss of parafibromin and a high MIB-1 index
are both independently sensitive and specific markers for the diagnosis of PC.
Loss of APC was only specific for PC. This panel of markers provides a novel,
useful approach in the diagnosis and differentiation of PCs from PAs.
PMID- 27490760
TI - Prognostic Significance of High Ki-67 Index and Histogenetic Subclassification in
Primary Central Nervous System Lymphoma.
AB - In diffuse large B-cell lymphoma (DLBCL), the germinal center B-cell (GCB)
subtype is associated with a better prognosis compared with the nongerminal
center B-cell-like (non-GCB) subtype. However, validity of this
immunohistochemical subgrouping in primary DLBCL of the central nervous system is
unclear. A total 45 cases of primary central nervous system lymphoma (PCNS)/DLBCL
were selected, and immunohistochemistries for CD10, Bcl-6, MUM1, and Ki-67 were
performed. Each of the cases was subclassified as either GCB or non-GCB based on
its immunoprofile. Among clinical and immunologic markers, patients under 70
years of age and who had methotrexate chemotherapy showed a significantly better
overall survival (OS). High Ki-67 (ie, a Ki-67 index >=90%) was an independent
prognostic factor for a poor OS in the whole cohort and in the patients with non
GCB subtype tumors (P=0.017, HR=4.267, 95% CI, 1.3-14.0; P=0.031, HR=3.752, 95%
CI, 1.3-12.5). Tumors were dominantly non-GCB subtype (41/45, 91.1%); only 4
(8.9%) were GCB subtype. The 2-year OS rates for these groups were 73% and 100%.
There was, however, no statistically significant difference between these groups
for OS and progression-free survival. The subclassification of PCNS/DLBCL into
GCB and non-GCB subtypes did not seem to have a prognostic value. In non-GCB
subtype PCNSL patients, high Ki-67 index was an adverse independent prognostic
marker that could be used to stratify patients for more suitable management.
PMID- 27490761
TI - Factors Associated With Detection of Helicobacter pylori in Gastric Biopsies: A
Case-Control Study of 396 Biopsies.
AB - AIM OF THE STUDY: Helicobacter pylori (HP) infection is associated with
significant gastric mucosal inflammation. We aimed to determine the
clinicopathologic features associated with HP in gastric biopsy. METHODS AND
RESULTS: Three hundred ninety-six gastric biopsies were evaluated including 165
HP-positive cases and 231 randomly selected HP-negative controls. HP was detected
using hematoxylin and eosin (H&E), Giemsa, and immunohistochemistry staining. The
univariate and multivariate analyses were conducted to study the relationship of
clinicopathologic characteristics and HP infection. Among the HP-positive cases,
131 cases were confirmed by H&E staining and 34 cases were confirmed by Giemsa or
immunohistochemistry staining. Compared with chronic inactive gastritis, chronic
active gastritis was more likely associated with having HP detected by H&E. Males
were more likely to have HP gastritis than females (odds ratio: 1.72, P=0.01).
The patients who had chronic active gastritis or chronic gastritis (moderate or
severe) were more likely to have HP infection than patients with mild chronic
gastritis (P<0.001). Conversely, patients who had intestinal metaplasia were less
likely to have HP infection than patients without intestinal metaplasia (odds
ratio: 0.22, P<0.001). However, concurrent atrophic gastritis was not related to
HP infection (P=0.37). HP infection history was not associated with HP infection
(P=0.74). CONCLUSIONS: HP detection in gastric biopsies is associated with active
inflammation, male sex, and the lack of intestinal metaplasia, but not atrophic
gastritis or HP infection history. Routine ancillary staining may not be required
for HP detection in all biopsy specimens. We do not recommend ancillary staining
for mild chronic inactive gastritis.
PMID- 27490762
TI - HER2 Status in Gastric and Gastroesophageal Junction Cancer: Results of the
Large, Multinational HER-EAGLE Study.
AB - Human epidermal growth factor receptor 2 (HER2) dysregulation is associated with
tumorigenesis in gastric/gastroesophageal junction cancer; however, the number of
patients with HER2-positive disease is unclear, possibly due to differing scoring
criteria/assays. Data are also lacking for early disease. We aimed to assess the
HER2-positivity rate using approved testing criteria in a large, real-life
multinational population. HER2-positivity was defined as an immunohistochemistry
staining score of 3+, or immunohistochemistry 2+ and HER2 amplification detected
by in situ hybridization. A total of 4949 patients were enrolled and results
showed that 14.2% of 4920 samples with immunohistochemistry results were HER2
positive. HER2-positivity was significantly higher in males (16.1% vs. 9.6% in
females), in gastroesophageal versus stomach tumors (22.1% vs. 12.9%), in biopsy
versus surgical samples (18.3% vs. 13.0%), in intestinal tumor subtypes versus
diffuse (21.5% vs. 4.8%) and mixed types (21.5% vs. 8.5%) (P<0.001), in mixed
versus diffuse types (8.5% vs. 4.8%), and in "other" versus diffuse types (11.7%
vs. 4.8%; P=0.002). There were no significant differences between stages.
Patients in the youngest age percentile had significantly lower HER2-positivity
rates than patients in the remaining percentiles (9.2% vs. 15.9%, 15.7%, and
15.1%; P<0.001). HER2-positivity was highest in France (20.2%) and lowest in Hong
Kong (10.4%). In conclusion, HER-EAGLE, the first study of its kind to be
conducted in a large, multinational population of almost 5000 patients, gives
valuable insights into the real-world HER2-positivity rate in a
gastric/gastroesophageal junction cancer patient population not selected for
disease stage or histology.
PMID- 27490763
TI - CD44 Immunoexpression is Unfavorable Predictor in Ovarian Serous Cancer.
AB - The aim of this study was to clarify the clinical role of CD44 expression in
ovarian serous cancer, and its relation to clinicopathologic prognostic factors,
disease free survival and overall survival (OS). Immunohistochemical staining for
CD44 was performed on 81 formalin-fixed, paraffin-embedded tumor sections. CD44
expression was found in 43% of ovarian carcinoma samples. Correlations between
categorical variables were studied using the chi and the Mann-Whitney U test. For
survival analysis, the Kaplan-Meier method, the log-rank test and the Cox
proportional hazard regression model were used. We did not find any statistically
significant difference in the distribution of respondents according to clinical
stage of the disease, tumor grade or the presence of vascular invasion in
relation to the expression of CD44. According to the results of uninominal
analysis, early International Federation of Gynecology and Obstetrics (FIGO)
stage of the disease (P=0.003) was associated with longer disease free survival,
while the expression of CD44 (P<0.001), FIGO stage III and IV (P=0.009) and the
finding of vascular invasion (P=0.005) was related to a shorter OS. In
conclusion, we proved that positive CD44 immunoexpression is a independent
prognostic indicator of shorter OS of patients with ovarian serous cancer.
PMID- 27490764
TI - The p16-Ki-67-HMB45 Immunohistochemistry Scoring System is Highly Concordant With
the Fluorescent In Situ Hybridization Test to Differentiate Between Melanocytic
Nevi and Melanomas.
AB - The treatment of melanoma requires early diagnosis and extensive surgical removal
of the primary tumor. The differential diagnosis between a melanoma and a nevus
is sometimes difficult from a histopathologic point of view and could require
ancillary diagnostic tools. Recently, both fluorescent in situ hybridization
(FISH) and p16-Ki67-HMB45 combined immunohistochemistry have been proposed as
examples of ancillary diagnostic methods to help classify melanocytic tumors as
benign or malignant. In this study, we compare FISH and p16-Ki-67-HMB45
immunohistochemistry in a set of melanomas and nevi. A total of 101 formalin
fixed and paraffin-embedded tumor samples (44 melanomas and 57 nevi) were
analyzed using FISH for chromosomes 6, 8, 9, and 11 and p16-Ki-67-HMB45
immunohistochemistry. Any chromosomal imbalances and/or a p16-Ki-67-HMB45
immunohistochemistry combined score of 4 or higher were considered to reflect a
"favor" malignant tumor. Using FISH, 42 out of 44 melanomas presented at least 1
chromosomal imbalance, whereas 2 melanomas and all nevi did not. Each melanoma,
including 6 challenging tumors, had a p16-Ki-67-HMB45 immunohistochemistry
combined score of 4 or higher and every nevus had a score inferior to 4. This
reflects an excellent strength of agreement between FISH, immunohistochemistry,
and definitive histopathologic diagnosis in our tumor set. We conclude that both
FISH and p16-Ki67-HMB45 combined immunohistochemistry are valuable ancillary
diagnostic tools to help pathologists classify melanocytic tumors as nevi or
melanomas.
PMID- 27490765
TI - Another Point of View About Cyclin D1 and p16 Expression in Blue Nevi and
Malignant Melanomas.
PMID- 27490766
TI - The Stem Cell-associated Transcription Factor SOX2 as a Diagnostic Marker of High
grade Squamous Intraepithelial Lesion of the Uterine Cervix in Comparison With
p16 and Ki-67.
AB - The transcription factor SOX2 has been identified as an oncogene involved in the
pathogenesis of squamous cell carcinoma (SCC) of multiple sites, including the
uterine cervix. The relationship between SOX2 overexpression and the continuum of
precancerous lesions of the cervix has not been previously elucidated. We
evaluated SOX2 immunohistochemical expression in normal cervix, low-grade
squamous intraepithelial lesion (LSIL) (mild squamous dysplasia), high-grade
squamous intraepithelial lesion (HSIL) (moderate and severe dysplasia) and SCC of
the cervix in comparison with p16 and Ki-67. Staining patterns were scored as
negative, basal one third of the epithelium, lower two third, or full thickness.
The results showed that SOX2 expression was limited to the basal one third in 84%
of LSIL cases, whereas 95% of HSIL showed SOX2 expression up to two third or full
thickness (P<0.0001). p16 and Ki-67 displayed similar results. The difference in
SOX2 expression between moderate and severe dysplasia was not statistically
significant (P=0.53). Invasive SCC positivity was as follows: SOX2 94%; p16 89%;
and Ki-67 100%. Our findings support a role for SOX2 in the progression of
squamous dysplasia to SCC. The Lower Anogenital Standardization Terminology
Project's recent assertion of a lack of a biological correlate to cervical
intraepithelial neoplasia II is also upheld by SOX2. For equivocal situations in
which a diagnosis of cervical intraepithelial neoplasia II would have been made,
Lower Anogenital Standardization Terminology recommends p16, or other biomarkers
such as Ki-67 to clarify the diagnosis. SOX2, with a clean nuclear staining
pattern, may also be suitable for this role.
PMID- 27490767
TI - Geographical disparity in breast reconstruction following mastectomy has reduced
over time.
AB - BACKGROUND: Breast reconstruction (BR) following mastectomy for breast cancer has
been shown to improve quality of life and body image; however, there is
significant geographic variation in BR rates. We explored factors associated with
BR following mastectomy. METHODS: This is a population-based data linkage study
consisting of cancer registry records linked to hospital inpatient episodes for
4104 women aged 20 years and over-diagnosed with a first primary invasive
localized stage breast cancer between 1997 and 2012 in Queensland, Australia, who
underwent a mastectomy. Multivariate logistic regression was used to model
predictors of BR. RESULTS: Overall, 481 women (11.7%) underwent reconstruction.
Proportions increased over time and were higher for younger women. Younger age,
more recent diagnosis, living in high or very high accessibility areas or less
disadvantaged areas, smaller tumours and attending a private or high-volume
hospital independently increased the odds of reconstruction. The geographical
disparity reduced significantly over time. CONCLUSION: Geographical barriers to
accessing BR have reduced; however, continued monitoring and further research to
inform strategies to further reduce subgroup disparities remain a priority.
PMID- 27490768
TI - New Thieme Research Awards: Call for Pacesetting Contributions to Drug Research.
PMID- 27490769
TI - The Effect of Early Excessive Weight Gain on the Development of Hypertension in
Pregnancy.
AB - Background Previous studies have shown an association between total excessive
gestational weight gain and hypertension in pregnancy. However, this may be a
reflection of excessive water retention associated with the pathophysiology of
hypertensive disorders of pregnancy. Early excessive weight gain, prior to the
third trimester, results in greater maternal fat deposition and inflammation,
which has also been associated with the development of hypertension. By focusing
on early excessive weight gain, the association between maternal weight gain and
the future development of hypertension can be examined. Objective To evaluate the
association between early excessive maternal weight gain and the development of
hypertension during pregnancy. Study Design This was a secondary analysis of a
longitudinal cohort study of 1,441 women without chronic hypertension who were
enrolled in a prospective study evaluating maternal angiogenic factors and the
prediction of preeclampsia. Initial body mass index (BMI) was calculated by
weight and height at the first study visit. Early excessive maternal weight gain
was defined as weight gain by 28 weeks that exceeded the Institute of Medicine
(IOM) guidelines and was calculated utilizing the maximum amount of weight gain
per week recommended by the IOM based on the patient's starting BMI (normal: 0.45
kg; overweight: 0.32 kg; obese: 0.27 kg). Hypertension was defined as a sustained
systolic blood pressure of >=140 mm Hg or a diastolic blood pressure of >=90 mm
Hg. Logistic regression was used to determine the association between early
excessive weight gain, initial BMI, and the development of hypertension,
including gestational hypertension and preeclampsia, during pregnancy. Results Of
1,441 women, 767 (53.2%) had weight gain that exceeded the IOM guidelines in the
first 28 weeks and 154 (10.8%) developed hypertension during pregnancy. Women
whose weight gain exceeded the IOM guidelines were more likely to develop
hypertension even after adjusting for relevant confounders (12.5 vs. 8.6%; p =
0.02; adjusted odds ratio [OR] = 1.70; 95% confidence interval [CI]: 1.18-2.44; p
< 0.01). Obese women had a 2.4-fold increased risk of developing hypertension,
even after controlling for excessive weight gain (adjusted OR = 2.44; 95% CI:
1.66-3.59; p < 0.01) Conclusions Early excessive maternal weight gain and initial
BMI are independently associated with the diagnosis of a hypertensive disorder of
pregnancy. Women should be counseled regarding the benefits of achieving a normal
BMI prior to pregnancy and appropriate weight gain during pregnancy, as well as
the potential harms of excessive weight gain related to perinatal outcomes.
PMID- 27490770
TI - Endocrine Disruptors: A Potential Risk Factor for Gestational Diabetes Mellitus.
AB - Gestational diabetes mellitus (GDM) has increased dramatically in the past 20
years together with the obesity epidemic. Mirroring the increase in incidence of
GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are
structurally similar to endogenous hormones and interfere with synthesis,
secretion, activity, or elimination of natural hormones, resulting in adverse
health effects, including diabetes, obesity, developmental disorders, etc.
Although the association between bisphenol A (BPA), a well-studied EDC, and type
2 diabetes has been repeatedly investigated in epidemiological and animal
studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact
of environmental toxins on perinatal health outcomes has largely been
overlooked.Recognizing this research gap, the American College of Obstetricians
and Gynecologists, American Society for Reproductive Medicine, and International
Federation of Gynecology and Obstetrics recently joined leading scientists and
clinicians in a call for action to prioritize research in the consequences of
exposure to toxic environmental agents on women's health. Evidence is emerging to
suggest signaling molecules and EDCs are involved in the control of microRNA
(miRNA) expression in trophoblast cells. We reviewed existing scientific evidence
of EDCs as a risk factor for GDM as well as the potential role of miRNA in this
association.
PMID- 27490772
TI - Management of Supplemental Oxygen for Infants with Persistent Pulmonary
Hypertension of Newborn: A Survey.
AB - Objective To evaluate practice variations amongst neonatologists regarding oxygen
management in neonates with persistent pulmonary hypertension of newborn (PPHN).
Study Design An online survey was administered to neonatologists to assess goal
oxygenation targets and oxygen titration practices in PPHN. Response variations
were assessed and intergroup comparisons performed. Results Thirty-three percent
(492) of neonatologists completed the survey. Twenty-eight percent reported using
specific oxygen titration guidelines. Majority of respondents used a combination
of oxygen saturation (SpO2) and arterial oxygen tension (PaO2) initially to
titrate oxygen. Seventy percent of the respondents used higher goal SpO2 > 95% or
95 to 98% and thirty-eight percent of the respondents used PaO2 > 80 mm Hg.
Physicians with extracorporeal membrane oxygenation experience and those with
greater than ten years neonatal intensive care unit experience inclined toward
use of SpO2 alone for oxygen titration and aimed for lower range of SpO2 and PaO2
targets. Greater proportion of neonatologists who employed specific oxygen
titration guidelines used lower SpO2 targets. Conclusion Wide practice variations
exist amongst neonatologists regarding optimal SpO2 and PaO2 targets and oxygen
titration practices in the management of PPHN.
PMID- 27490771
TI - Sex-Specific Associations of Maternal Gestational Glycemia with Hormones in
Umbilical Cord Blood at Delivery.
AB - Background Few studies have examined sex-specific associations of maternal
gestational glycemia with cord blood hormones, which might predict later health.
Methods In 976 women without pre-existing diabetes in the Project Viva cohort, we
used linear regression to examine associations of maternal gestational glycemia
with cord hormone concentrations, adjusted for maternal characteristics and
stratified by infant sex. Results A total of 6.1% of women had gestational
diabetes mellitus (GDM), 8.8% isolated hyperglycemia, 3.2% gestational impaired
glucose tolerance, and 81.9% were normoglycemic. In boys, compared with infants
of normoglycemic mothers, infants of GDM mothers had higher cord levels of IGF-2
(beta 35.55 ng/mL; 95% CI: 2.60, 68.50), IGFBP-3 (111.2 ng/mL; 5.53, 216.8),
insulin (4.66 uU/mL; 2.38, 6.95), C-peptide (0.46 ng/mL; 0.25, 0.67), and leptin
(3.51 ng/mL; 1.37, 5.64), but lower IGF-1 (-6.71 ng/mL; -12.7, - 0.76, adjusted
for IGFBP-3). In girls, GDM offspring had higher cord blood levels of IGF-1
adjusted for IGFBP-3 (12.45 ng/mL; 4.85, 20.04). Boys, but not girls, of mothers
with abnormal glucose tolerance but not GDM also had higher levels of some
hormones. Conclusion GDM was associated with growth factors and adipokines in
cord blood from boys, but only IGF-1 in girls. These findings suggest sex
differences in responses to fetal overnutrition.
PMID- 27490773
TI - Neonatal Hospital Course and Outcomes of Live-born Infants with Trisomy 18 at Two
Tertiary Care Centers in the United States.
AB - Objectives Trisomy 18 is presumed to be a lethal chromosomal abnormality; medical
management of infants with this aneuploidy is controversial. Our objective was to
describe our approach and experience with trisomy 18 infants. Study Design We
reviewed the initial hospital course, management, and factors predicting
discharge from the hospital from two large tertiary care neonatal intensive care
units in the southern United States over 26 years. Results Of the 29 infants with
trisomy 18, 21 (72%) died in the hospital and 8 (28%) were discharged home. 19
(66%) infants received mechanical ventilation and 10 (34%) received inotropic
medications. Eight infants had critical congenital heart defects; only one
survived to discharge. Three infants underwent major surgeries; one cardiac
surgery, one tracheoesophageal fistula repair, and one myelomeningocele repair.
Median length of hospital stay was 14 days (range, 0-78) for all the infants and
31 days (range, 18-66) for those that were discharged home. Factors associated
with discharge from the hospital were female sex, higher gestational age, and
absence of critical congenital heart defects. Median survival time was 13 days
and was significantly longer for females compared with males. Our 1-month and 1
year survival rates were 31% and 3.9% respectively. Conclusion A significant
proportion of infants with trisomy 18 were discharged home. These data are
helpful in counseling parents of infants with trisomy 18.
PMID- 27490774
TI - First Trimester Detection of Placental Disease: Challenges and Opportunities.
AB - It is generally agreed that placental pathology accounts for the majority of
perinatal morbidity and mortality. If a placental prodrome could be diagnosed in
vivo, risk for maternal or fetal complications could be estimated and acted upon
before clinical symptoms are apparent. This is especially relevant in early
diagnoses of gestational diabetes mellitus, which can be controlled through
carefully monitored diet and activity changes. To meet this important need, there
have been increased efforts to identify early gestation biomarkers of placental
dysfunction using innovative imaging technologies. Here we outline innovative
quantitative markers of placental shape and their relationship to placental
function, clinical implications of these quantifiers, and the most recent
mathematical models that utilize placental images to delineate at risk from
normal pregnancies. We propose that novel contexts of readily available placental
measures and routine collection of in vivo placental images in all pregnancies
may be all that are needed to advance the identification of early risk
determination of complicated pregnancies from placental images.
PMID- 27490775
TI - Longitudinal Patterns of Glycemic Control and Blood Pressure in Pregnant Women
with Type 1 Diabetes Mellitus: Phenotypes from Functional Data Analysis.
AB - Objective To identify phenotypes of type 1 diabetes control and associations with
maternal/neonatal characteristics based on blood pressure (BP), glucose, and
insulin curves during gestation, using a novel functional data analysis approach
that accounts for sparse longitudinal patterns of medical monitoring during
pregnancy. Methods We performed a retrospective longitudinal cohort study of
women with type 1 diabetes whose BP, glucose, and insulin requirements were
monitored throughout gestation as part of a program-project grant. Scores from
sparse functional principal component analysis (fPCA) were used to classify
gestational profiles according to the degree of control for each monitored
measure. Phenotypes created using fPCA were compared with respect to maternal and
neonatal characteristics and outcome. Results Most of the gestational profile
variation in the monitored measures was explained by the first principal
component (82-94%). Profiles clustered into three subgroups of high, moderate, or
low heterogeneity, relative to the overall mean response. Phenotypes were
associated with baseline characteristics, longitudinal changes in glycohemoglobin
A1 and weight, and to pregnancy-related outcomes. Conclusion Three distinct
longitudinal patterns of glucose, insulin, and BP control were found. By
identifying these phenotypes, interventions can be targeted for subgroups at
highest risk for compromised outcome, to optimize diabetes management during
pregnancy.
PMID- 27490776
TI - The relationship between attentional bias toward safety and driving behavior.
AB - As implicit cognitive processes garner more and more importance, studies in the
fields of healthy psychology and organizational safety research have focused on
attentional bias, a kind of selective allocation of attentional resources in the
early stage of cognitive processing. However, few studies have explored the role
of attentional bias on driving behavior. This study assessed drivers' attentional
bias towards safety-related words (ABS) using the dot-probe paradigm and self
reported daily driving behaviors. The results revealed significant negative
correlations between attentional bias scores and several indicators of dangerous
driving. Drivers with fewer dangerous driving behaviors showed greater ABS. We
also built a significant linear regression model between ABS and the total DDDI
score, as well as ABS and the number of accidents. Finally, we discussed the
possible mechanism underlying these associations and several limitations of our
study. This study opens up a new topic for the exploration of implicit processes
in driving safety research.
PMID- 27490777
TI - Structural and Dynamic Characterization of the Molecular Hub Early Region 1A
(E1A) from Human Adenovirus.
AB - The small-DNA human adenovirus encodes one of the most versatile molecular hubs,
the E1A protein. This protein is essential for productive viral infection in
human cells and a vast amount of biologically relevant data are available on its
interactions with host proteins. Up to now, however, no high-resolution
structural and dynamic information on E1A is available despite its important
biological role. Among the different spliced variants of E1A, two are expressed
at high level in the early stage of infection. These are 243 and 289 residues
isoforms. Herein, we present their NMR characterization, showing that they are
both highly disordered, but also demonstrate a certain heterogeneous behavior in
terms of structural and dynamic properties. Furthermore, we present the
characterization of the isolated domain of the longer variant, known as CR3. This
study opens the way to understanding at the molecular level how E1A functions.
PMID- 27490778
TI - CSTMP induces apoptosis and mitochondrial dysfunction in human myeloma RPMI8226
cells via CHOP-dependent endoplasmic reticulum stress.
AB - BACKGROUND: The natural product tetramethylpyrazine (TMP) and resveratrol have a
variety of biologic activities, including anti-cancer effects. However the
pharmacological function of CSTMP (a newly designed and synthesized TMP and
resveratrol derivative) in cancer have not been elucidated. METHODS: In RPMI8226
cells, the cytotoxic effects and apoptosis were detected by MTT and Double
staining for Annexin V-FITC and propidium iodide (PI). The protein and mRNA
expression levels were detected by Real Time PCR and Western blot, respectively.
The localization of cleaved caspase-12 was evaluated by immunofluorescent
staining. The activation of caspase were measured by colorimetric assays and
Western blot. RESULTS: CSTMP showed significantly cytotoxic effects and induced
apoptosis in RPMI8226 cells. Caspase activation, Cytochrome c release and Bax,
Bcl-2 and Bcl-XL levels analyses demonstrated that the anti-cancer effect of
CSTMP in RPMI8226 cells was mediated by promoting caspase- and mitochondria
dependent apoptosis. In addition, CSTMP induced the increased expression of
endoplasmic reticulum (ER) stress related proteins (CHOP, GRP78, GRP94 and
cleaved caspase-12) and the activation of multiple branches of ER stress
transducers (PERK-eIF2alpha, IRE1alpha and ATF6). Moreover, knockdown of CHOP by
siRNA markedly inhibited CSTMP-induced cytotoxic effects, caspases activity and
mitochondrial dysfunction in RPMI8226 cells. CONCLUSIONS: Our results indicated
that CSTMP could induce apoptosis and mitochondrial dysfunction in RPMI8226 cells
via CHOP-dependent ER stress.
PMID- 27490780
TI - miR-1299 suppresses cell proliferation of hepatocellular carcinoma (HCC) by
targeting CDK6.
AB - microRNA (miRNA) plays critical role in HCC initiation and development, many
miRNAs have been reported to regulate HCC progression. In this study, we studied
the role of miR-1299 in cell proliferation of HCC. We found miR-1299 was
significantly downregulated in HCC cells and tissues. miR-1299 overexpression
inhibited cell proliferation and arrested cell cycle in G0/G1 phase analyzed by
MTT assay, soft agar assay, BrdU cell proliferation assay and cell cycle assay,
while miR-1299 knockdown promoted cell proliferation and accelerated G1/S
transition. Further analysis suggested the key regulator of G1/S transition,
cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited
CDK6 expression and bound to the 3'UTR of CDK6. When double knockdown of miR-1299
and CDK6 promoted cell proliferation copied the phenotype caused by miR-1299
overexpression, suggesting miR-1299 inhibits cell proliferation by targeting
CDK6. In summary, our data revealed miR-1299 inhibits cell proliferation, and
might be a target for HCC therapy.
PMID- 27490779
TI - Swertiamarin ameliorates oleic acid induced lipid accumulation and oxidative
stress by attenuating gluconeogenesis and lipogenesis in hepatic steatosis.
AB - Swertiamarin, a bitter secoiridoid glycoside, is an antidiabetic drug with lipid
lowering activity meliorates insulin resistance in Type 2 Diabetes condition.
Therefore, the study was designed to explore the antioxidant and hypolipidemic
activity of swertiamarin in ameliorating NAFLD caused due to hepatic lipid
accumulation, inflammation and insulin resistance. Steatosis was induced in HepG2
cells by supplementing 1mM oleic acid (OA) for 24h which was marked by
significant accumulation of lipid droplets. This was determined by Oil Red O
(ORO) staining and triglyceride accumulation. Swertiamarin (25MUg/ml) decreased
triglyceride content by 2 folds and effectively reduced LDH release (50%)
activity by protecting membrane integrity thus, preventing apoptosis evidenced by
reduced cleavage of Caspase 3 and PARP1. We observed that swertiamarin
significantly increased the expressions of major insulin signaling proteins like
Insulin receptor (IR), PI(3)K, pAkt with concomitant reduction in p307 IRS-1.
AMPK was activated by swertiamarin action, thus restoring insulin sensitivity in
hepatocytes. In addition, qPCR results confirmed OA up-regulated Sterol
Regulatory Element Binding Protein (SREBP)-1c and fatty acid synthase (FAS),
resulting in increased fatty acid synthesis. Swertiamarin effectively modulated
PPAR-alpha, a major potential regulator of carbohydrate metabolism which, in
turn, decreased the levels of the gluconeogenic enzyme PEPCK, further restricting
hepatic glucose production and fatty acid synthesis. Cumulatively, swertiamarin
targets potential metabolic regulators AMPK and PPAR-alpha, through which it
regulates hepatic glycemic burden, fat accumulation, insulin resistance and ROS
in hepatic steatosis which emphasizes clinical significance of swertiamarin in
regulating metabolism and as a suitable candidate for treating NAFLD.
PMID- 27490782
TI - The role of short-chain fatty acid on blood pressure regulation.
AB - PURPOSE OF REVIEW: The gut microbiota and its metabolites have been implicated in
the regulation of host physiological functions such as inflammatory and metabolic
responses. The short-chain fatty acid (SCFA) receptor is expressed in the kidney
and blood vessels as well, and has been reported to function as a regulator of
blood pressure (BP). This review highlights the role of SCFAs derived from gut
microbial fermentation in the regulation of BP. RECENT FINDINGS: Olfactory
receptor 78 (Olfr78) is a member of the G-protein-coupled receptor family, and it
plays a key role as a chemosensor in various tissues. Both Olfr78 and G protein
coupled receptor 41 (GPR41) are expressed in smooth muscle cells of blood vessels
and they recognize SCFAs. Oral administration of SCFAs was found to change BP in
vivo, an effect that was altered in Olfr78 and GPR41-deficient mice. SUMMARY: The
regulation of BP via SCFA receptors has provided new insights into the
interactions between the gut microbiota and BP control systems. We summarize
these interactions and describe their contributions to a novel pathway involved
in BP regulation. These recent findings could open new avenues for the
development of therapeutic strategies for the treatment of cardiovascular
diseases.
PMID- 27490781
TI - Homology modeling and virtual screening for inhibitors of lipid kinase PI(4)K
from Plasmodium.
AB - Malaria parasite strains have emerged to tolerate the therapeutic effects of the
prophylactics and drugs presently available. Recent studies have shown that
KAI715 and its analogs inhibit malaria parasites growth by binding to lipid
kinase PI(4)K (phosphatidylinositol-4-OH kinase) of the parasites. Therefore,
targeting PI(4)K may open up new avenues of target-based drug discovery to
identify novel anti-malaria drugs. In this investigation, we describe the
discovery of novel potent PfPI(4)K (PI(4)K from P. falciparum) inhibitors by
employing a proposed hybrid virtual screening (VS) method, including
pharmacophore model, drug-likeness prediction and molecular docking approach. 3D
structure of PfPI(4)K has been established by homology modeling. Pharmacophore
model HypoA of PfPI(4)K inhibitors has been developed based on the ligand
complexed with its corresponding receptor. 174 compounds with good ADMET
properties were carefully selected by a hybrid virtual screening method. Finally,
the 174 hits were further validated by using a new pharmacophore model HypoB
built based on the docking pose of BQR685, and 95 compounds passed the last
filter. These compounds would be further evaluated by biological activity assays.
The molecular interactions of the top two potential inhibitors with the active
site residues are discussed in detail. These identified hits can be further used
for designing the more potent inhibitors against PfPI(4)K by scaffold hopping,
and deserve consideration for further structure-activity relationship (SAR)
studies.
PMID- 27490783
TI - Neuroinflammatory mechanisms of hypertension: potential therapeutic implications.
AB - PURPOSE OF REVIEW: Inflammation of forebrain and hindbrain nuclei has recently
been highlighted as an emerging factor in the pathogenesis of neurogenic
hypertension. The aim of this review is to summarize the state of the art in this
field and to discuss recently discovered pathophysiological mechanisms, opening
new perspectives for therapeutic application. RECENT FINDINGS: Microglia Toll
like receptor 4 causally links angiotensin II (AngII)-mediated microglia cell
activation and oxidative stress within the hypothalamic paraventricular nucleus
(PVN). Toll-like receptor 4 can also be activated by lipopolysaccharides. PVN
infusion of nuclear factor kappaB inhibitor lowers the blood pressure and
ameliorates cardiac hypertrophy. Ang-(1-7) exerts direct effects on microglia,
causing a reduction in both baseline and prorenin-induced release of
proinflammatory cytokines. A compromised blood-brain barrier (BBB) constitutes a
complementary mechanism that exacerbates AngII-driven neurohumoral activation,
contributing to the development of hypertension. SUMMARY: PVN and BBB seem to be
pivotal targets for therapeutic intervention in hypertension. Recent advances in
imaging techniques enable visualization of the inflammatory state in microglia
and BBB integrity in humans. AngII type I receptor blockers and AngII-converting
enzyme inhibitors are the most likely candidates for controlled randomized trials
in humans aimed at amelioration of brain inflammation in the forthcoming years.
PMID- 27490785
TI - Public Attitudes About Eye and Vision Health.
AB - Importance: Understanding the importance of eye health to the US population
across ethnic and racial groups helps guide strategies to preserve vision in
Americans and inform policy makers regarding priority of eye research to
Americans. Objective: To understand the importance and awareness of eye health in
the US population across ethnic and racial groups. Design, Setting, and
Participants: Online nationwide poll created by experienced policy makers in
August 2014 designed to understand the importance of eye health in the US
population, although the poll was not subjected previously to formal construct
validity testing. The population survey comprised 2044 US adults including non
Hispanic white individuals and minority groups with minority oversampling to
provide predicted margins of error no greater than 5%. Main Outcomes and
Measures: Respondent attitudes on the importance of eye health, concerns about
losing vision, support for eye health research, and awareness of eye diseases and
risk factors. Results: Of the 2044 survey respondents, the weighten mean age was
46.2 years, 48% were male, and 11% were uninsured. Sixty three percent reported
wearing glasses. Most individuals surveyed (87.5%; 95% CI, 84.5%-90%) believed
that good vision is vital to overall health while 47.4% (95% CI, 43.7%-51.1%)
rated losing vision as the worst possible health outcome. Respondents ranked
losing vision as equal to or worse than losing hearing, memory, speech, or a
limb. When asked about various possible consequences of vision loss, quality of
life ranked as the top concern followed by loss of independence. Nearly two
thirds of respondents were aware of cataracts (65.8%) or glaucoma (63.4%); only
half were aware of macular degeneration; 37.3% were aware of diabetic
retinopathy; and 25% were not aware of any eye conditions. Approximately 75.8%
and 58.3%, respectively, identified sunlight and family heritage as risk factors
for losing vision; only half were aware of smoking risks on vision loss.
Conclusions and Relevance: In this well-characterized survey across all US ethnic
and racial groups, vision health was a priority with high support for ongoing
research for vision and eye health. Many Americans were unaware of important eye
diseases and their behavioral or familial risk factors. The consistency of these
findings among the varying ethnic/racial groups underscores the importance of
educating the public on eye health and mobilizing public support for vision
research.
PMID- 27490786
TI - Activation of H2 over the Ru-Zn Bond in the Transition Metal-Lewis Acid
Heterobimetallic Species [Ru(IPr)2(CO)ZnEt](.).
AB - Reaction of [Ru(IPr)2(CO)H]BAr(F)4 with ZnEt2 forms the heterobimetallic species
[Ru(IPr)2(CO)ZnEt]BAr(F)4 (2), which features an unsupported Ru-Zn bond. 2 reacts
with H2 to give [Ru(IPr)2(CO)(eta(2)-H2)(H)2ZnEt]BAr(F)4 (3) and
[Ru(IPr)2(CO)(H)2ZnEt]BAr(F)4 (4). DFT calculations indicate that H2 activation
at 2 proceeds via oxidative cleavage at Ru with concomitant hydride transfer to
Zn. 2 can also activate hydridic E-H bonds (E = B, Si), and computed mechanisms
for the facile H/H exchange processes observed in 3 and 4 are presented.
PMID- 27490784
TI - Paracellular transport in the collecting duct.
AB - PURPOSE OF REVIEW: The paracellular pathway through the tight junction provides
an important route for chloride reabsorption in the collecting duct of the
kidney. This review describes recent findings of how defects in paracellular
chloride permeation pathway may cause kidney diseases and how such a pathway may
be regulated to maintain normal chloride homeostasis. RECENT FINDINGS: The tight
junction in the collecting duct expresses two important claudin genes - claudin-4
and claudin-8. Transgenic knockout of either claudin gene causes hypotension,
hypochloremia, and metabolic alkalosis in experimental animals. The claudin-4
mediated chloride permeability can be regulated by a protease endogenously
expressed by the collecting duct cell - channel-activating protease 1. Channel
activating protease 1 regulates the intercellular interaction of claudin-4 and
its membrane stability. Kelch-like 3, previously identified as a causal gene for
Gordon's syndrome, also known as pseudohypoaldosteronism II, directly interacts
with claudin-8 and regulates its ubiquitination and degradation. The dominant
pseudohypoaldosteronism-II mutation (R528H) in Kelch-like 3 abolishes claudin-8
binding, ubiquitination, and degradation. SUMMARY: The paracellular chloride
permeation pathway in the kidney is an important but understudied area in
nephrology. It plays vital roles in renal salt handling and regulation of
extracellular fluid volume and blood pressure. Two claudin proteins, claudin-4
and claudin-8, contribute to the function of this paracellular pathway. Deletion
of either claudin protein from the collecting duct causes renal chloride
reabsorption defects and low blood pressure. Claudins can be regulated on
posttranslational levels by several mechanisms involving protease and ubiquitin
ligase. Deregulation of claudins may cause human hypertension as exemplified in
the Gordon's syndrome.
PMID- 27490787
TI - Medial Patellofemoral Reconstruction in Children and Adolescents.
PMID- 27490788
TI - Improving Operating Room Efficiency, Part 1: General Managerial and Preoperative
Strategies.
PMID- 27490789
TI - Improving Operating Room Efficiency, Part 2: Intraoperative and Postoperative
Strategies.
PMID- 27490790
TI - Treatment of Syndesmotic Injuries of the Ankle: A Critical Analysis Review.
PMID- 27490791
TI - Magnetic Resonance Imaging Following Spine Trauma.
PMID- 27490792
TI - Operative and Nonoperative Treatment of Acromioclavicular Dislocation: A Critical
Analysis Review.
PMID- 27490793
TI - Effect of mitomycin c and 5-flurouracil adjuvant therapy on the outcomes of Ahmed
glaucoma valve implantation.
AB - BACKGROUND: To examine the effect of mitomycin c and 5-flurouracil on treatment
outcomes following Ahmed glaucoma valve implantation. DESIGN: Retrospective
consecutive case series. PARTICIPANTS: Fifty patients who received Ahmed glaucoma
valve implantation from 1999 to 2013 in the San Francisco Veterans Administration
Hospital. METHODS: The +INJECTION group received intraoperative mitomycin c
followed by postoperative mitomycin c and/or 5-flurouracil, whereas the
INJECTION group did not. MAIN OUTCOME MEASURES: Primary outcome was treatment
success at 1 year post-implantation. Intraocular pressure, hypertensive phase,
and the number of glaucoma medications were also examined. RESULTS: Twenty-six
patients/eyes in the +INJECTION group and 24 patients/eyes in the -INJECTION
group were included. Treatment success was higher in the +INJECTION compared with
the -INJECTION group (86 vs. 58%; P = 0.04). Intraocular pressure was lower in
the +INJECTION compared with the -INJECTION group at 1, 3, 6 and 12 months (P ?
0.00001, P = 0.00003, 0.0008 and 0.024). Hypertensive phase occurred less often
in the +INJECTION compared with the -INJECTION group (3.8 vs. 54%; P = 0.021).
The +INJECTION group required fewer medications compared with the -INJECTION
group (P = 0.02, 0.002, 0.003 and 0.008 at 1, 3, 6 and 12 months). Complication
rates were comparable between groups (46.2 and 54.2%; P = 0.63). CONCLUSIONS:
Adjuvant treatment with antifibrotics following Ahmed glaucoma valve implantation
decreased the hypertensive phase and improved surgical outcomes without impacting
complication rates at 1 year. This study postulates a role for antifibrotics in
the postoperative management of Ahmed glaucoma valves.
PMID- 27490796
TI - Coupling Capillary Zone Electrophoresis to a Q Exactive HF Mass Spectrometer for
Top-down Proteomics: 580 Proteoform Identifications from Yeast.
AB - We used reversed-phase liquid chromatography to separate the yeast proteome into
23 fractions. These fractions were then analyzed using capillary zone
electrophoresis (CZE) coupled to a Q-Exactive HF mass spectrometer using an
electrokinetically pumped sheath flow interface. The parameters of the mass
spectrometer were first optimized for top-down proteomics using a mixture of
seven model proteins; we observed that intact protein mode with a trapping
pressure of 0.2 and normalized collision energy of 20% produced the highest
intact protein signals and most protein identifications. Then, we applied the
optimized parameters for analysis of the fractionated yeast proteome. From this,
580 proteoforms and 180 protein groups were identified via database searching of
the MS/MS spectra. This number of proteoform identifications is two times larger
than that of previous CZE-MS/MS studies. An additional 3,243 protein species were
detected based on the parent ion spectra. Post-translational modifications
including N-terminal acetylation, signal peptide removal, and oxidation were
identified.
PMID- 27490795
TI - Six-SOMAmer Index Relating to Immune, Protease and Angiogenic Functions Predicts
Progression in IPF.
AB - RATIONALE: Biomarkers in easily accessible compartments like peripheral blood
that can predict disease progression in idiopathic pulmonary fibrosis (IPF) would
be clinically useful regarding clinical trial participation or treatment
decisions for patients. In this study, we used unbiased proteomics to identify
relevant disease progression biomarkers in IPF. METHODS: Plasma from IPF patients
was measured using an 1129 analyte slow off-rate modified aptamer (SOMAmer)
array, and patient outcomes were followed over the next 80 weeks. Receiver
operating characteristic (ROC) curves evaluated sensitivity and specificity for
levels of each biomarker and estimated area under the curve (AUC) when prognostic
biomarker thresholds were used to predict disease progression. Both logistic and
Cox regression models advised biomarker selection for a composite disease
progression index; index biomarkers were weighted via expected progression-free
days lost during follow-up with a biomarker on the unfavorable side of the
threshold. RESULTS: A six-analyte index, scaled 0 to 11, composed of markers of
immune function, proteolysis and angiogenesis [high levels of ficolin-2 (FCN2),
cathepsin-S (Cath-S), legumain (LGMN) and soluble vascular endothelial growth
factor receptor 2 (VEGFsR2), but low levels of inducible T cell costimulator
(ICOS) or trypsin 3 (TRY3)] predicted better progression-free survival in IPF
with a ROC AUC of 0.91. An index score >= 3 (group >= 2) was strongly associated
with IPF progression after adjustment for age, gender, smoking status,
immunomodulation, forced vital capacity % predicted and diffusing capacity for
carbon monoxide % predicted (HR 16.8, 95% CI 2.2-126.7, P = 0.006). CONCLUSION:
This index, derived from the largest proteomic analysis of IPF plasma samples to
date, could be useful for clinical decision making in IPF, and the identified
analytes suggest biological processes that may promote disease progression.
PMID- 27490797
TI - Etiology and Features of Eyes with Rubeosis Iridis among Korean Patients: A
Population-Based Single Center Study.
AB - PURPOSE: To estimate the etiology and features of the eyes with rubeosis iridis
among Korean patients. MATERIALS AND METHODS: This study is a retrospective
review of 533 Korean patients with rubeosis iridis who visited an eye hospital in
Seoul, Korea. We defined rubeosis iridis as visible blood vessels on the iris
surface detected during a slit-lamp examination. All cases were reviewed for age
at the time of diagnosis, medical history, the most likely cause of rubeosis
iridis, visual acuity, and intraocular pressure. RESULTS: The most commonly
observed cause of rubeosis iridis was diabetic retinopathy (DR; n = 337, 63.2%),
followed by retinal vein occlusion (RVO; n = 101, 18.9%), ocular ischemic
syndrome (OIS; n = 24, 4.5%), retinal detachment (n = 17, 3.2%), and uveitis (n =
15, 2.8%). The cause was classified as miscellaneous in 18 cases (3.4%); in 21
eyes (3.9%), the cause was not clear. Age at the time of rubeosis iridis
diagnosis was lower in patients with DR (56.5 years) than in those with RVO (61.0
years) and OIS (64.8 years; P < 0.01). Intraocular pressure of the eyes with DR
(37.3 mmHg) and RVO (39.5 mmHg) was higher than that of the eyes with OIS (25.8
mmHg; P < 0.01). CONCLUSION: In our population-based single center study, DR was
the leading cause of rubeosis iridis followed by RVO and OIS among Korean
patients. The clinical characteristics of the eyes with rubeosis iridis differed
according to etiology. This finding may be useful when assessing eyes with
rubeosis iridis.
PMID- 27490798
TI - Cyclic Triradicals Composed of Iminonitroxide-Gold(I) with Intramolecular
Ferromagnetic Interactions.
AB - A triangular gold(iminonitroxide-2-ide) trimer complex (5) was prepared and
investigated to determine its magnetic properties. The results showed that the
metalloid triradical is highly stable, even in solution under aerated conditions.
The intramolecular exchange interaction of 5 was found to be positive (Jintra /kB
~+29 K), thus showing that 5 is in a quartet ground state. In addition, a silver
sandwich complex (5-Ag(+) -5) was prepared and its electronic and magnetic
properties were also clarified.
PMID- 27490799
TI - Correction: Normal Lung Quantification in Usual Interstitial Pneumonia Pattern:
The Impact of Threshold-based Volumetric CT Analysis for the Staging of
Idiopathic Pulmonary Fibrosis.
AB - [This corrects the article DOI: 10.1371/journal.pone.0152505.].
PMID- 27490800
TI - Human Management of a Wild Plant Modulates the Evolutionary Dynamics of a Gene
Determining Recessive Resistance to Virus Infection.
AB - This work analyses the genetic variation and evolutionary patterns of recessive
resistance loci involved in matching-allele (MA) host-pathogen interactions,
focusing on the pvr2 resistance gene to potyviruses of the wild pepper Capsicum
annuum glabriusculum (chiltepin). Chiltepin grows in a variety of wild habitats
in Mexico, and its cultivation in home gardens started about 25 years ago.
Potyvirus infection of Capsicum plants requires the physical interaction of the
viral VPg with the pvr2 product, the translation initiation factor eIF4E1.
Mutations impairing this interaction result in resistance, according to the MA
model. The diversity of pvr2/eIF4E1 in wild and cultivated chiltepin populations
from six biogeographical provinces in Mexico was analysed in 109 full-length
coding sequences from 97 plants. Eleven alleles were found, and their interaction
with potyvirus VPg in yeast-two-hybrid assays, plus infection assays of plants,
identified six resistance alleles. Mapping resistance mutations on a pvr2/eIF4E1
model structure showed that most were around the cap-binding pocket and strongly
altered its surface electrostatic potential, suggesting resistance-associated
costs due to functional constraints. The pvr2/eIF4E1 phylogeny established that
susceptibility was ancestral and resistance was derived. The spatial structure of
pvr2/eIF4E1 diversity differed from that of neutral markers, but no evidence of
selection for resistance was found in wild populations. In contrast, the
resistance alleles were much more frequent, and positive selection stronger, in
cultivated chiltepin populations, where diversification of pvr2/eIF4E1 was
higher. This analysis of the genetic variation of a recessive resistance gene
involved in MA host-pathogen interactions in populations of a wild plant show
that evolutionary patterns differ according to the plant habitat, wild or
cultivated. It also demonstrates that human management of the plant population
has profound effects on the diversity and the evolution of the resistance gene,
resulting in the selection of resistance alleles.
PMID- 27490801
TI - Screening women for cervical cancer carcinoma with a HPV mRNA test: first results
from the Venice pilot program.
AB - BACKGROUND: HPV DNA-based screening is more effective than a Pap test in
preventing cervical cancer, but the test is less specific. New HPV tests have
been proposed for primary screening. The HPV mRNA test showed a similar or
slightly lower sensitivity than the HPV DNA tests but with a higher specificity.
We report the results of an organised HPV mRNA-based screening pilot program in
Venice, Italy. METHODS: From October 2011 to May 2014, women aged 25-64 years
were invited to undergo a HPV mRNA test (Aptima). Those testing positive
underwent cytological triage. Women with positive cytology were referred to
colposcopy, whereas those with negative cytology were referred to repeat the HPV
mRNA test 1 year later. The results of the HPV mRNA test program were compared
with both the local historical cytology-based program and with four neighbouring
DNA HPV-based pilot projects. RESULTS: Overall, 23 211 women underwent a HPV mRNA
test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA
programs (6.8%; relative rate (RR) 1.11, 95% confidence interval (CI) 1.05-1.17).
The total colposcopy referral was 5.1%, double than with cytology (2.6%; RR 2.02,
95% CI 1.82-2.25) but similar to the HPV DNA programs (4.8%; RR 1.02; 95% CI 0.96
1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV
mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19
1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40
1.16). The overall RR was 1.29 (95% CI 1.05-1.59), which was much higher than
with cytology (detection rate 5.50/00 vs 2.10/00; RR 2.50, 95% CI 1.76-3.62).
CONCLUSIONS: A screening programme based on the HPV mRNA obtained results similar
to those observed with the HPV DNA test. In routine screening programmes, even a
limited increase in HPV prevalence may conceal the advantage represented by the
higher specificity of HPV mRNA.
PMID- 27490802
TI - CXCL9 and CXCL10 predict survival and are regulated by cyclooxygenase inhibition
in advanced serous ovarian cancer.
AB - BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are associated with improved
survival in several epithelial cancers. The two chemokines CXCL9 and CXCL10
facilitate chemotactic recruitment of TILs, and their intratumoral accumulation
is a conceivable way to improve TIL-dependent immune intervention in cancer.
However, the prognostic impact of CXCL9 and CXCL10 in high-grade serous ovarian
cancer (HGSC) is largely unknown. METHODS: One hundred and eighty four cases of
HGSC were immunohistochemically analyzed for CXCL9, CXCL10. TILs were assessed
using CD3, CD56 and FOXP3 staining. Chemokine regulation was investigated using
the ovarian cancer cell lines OV-MZ-6 and SKOV-3. RESULTS: High expression of
CXCL9 and CXCL10 was associated with an approximately doubled overall survival
(n=70, CXCL9: HR 0.41; P=0.006; CXCL10: HR 0.46; P=0.010) which was confirmed in
an independent validation set (n=114; CXCL9: HR 0.60; P=0.019; CXCL10: HR 0.52;
P=0.005). Expression of CXCR3 ligands significantly correlated with TILs. In
human ovarian cancer cell lines the cyclooxygenase (COX) metabolite Prostaglandin
E2 was identified as negative regulator of chemokine secretion, whereas COX
inhibition by indomethacin significantly upregulated CXCL9 and CXCL10. In
contrast, celecoxib, the only COX inhibitor prospectively evaluated for therapy
of ovarian cancer, suppressed NF-kappaB activation and inhibited chemokine
release. CONCLUSION: Our results support the notion that CXCL9 and CXCL10 exert
tumour-suppressive function by TIL recruitment in human ovarian cancer. COX
inhibition by indomethacin, not by celecoxib, may be a promising approach to
concomitantly improve immunotherapies.
PMID- 27490803
TI - Symptoms and patient factors associated with longer time to diagnosis for
colorectal cancer: results from a prospective cohort study.
AB - BACKGROUND: The objective of this study is to investigate symptoms, clinical
factors and socio-demographic factors associated with colorectal cancer (CRC)
diagnosis and time to diagnosis. METHODS: Prospective cohort study of
participants referred for suspicion of CRC in two English regions. Data were
collected using a patient questionnaire, primary care and hospital records.
Descriptive and regression analyses examined associations between symptoms and
patient factors with total diagnostic interval (TDI), patient interval (PI),
health system interval (HSI) and stage. RESULTS: A total of 2677 (22%)
participants responded; after exclusions, 2507 remained. Participants were
diagnosed with CRC (6.1%, 56% late stage), other cancers (2.0%) or no cancer
(91.9%). Half the cohort had a solitary first symptom (1332, 53.1%); multiple
first symptoms were common. In this referred population, rectal bleeding was the
only initial symptom more frequent among cancer than non-cancer cases (34.2% vs
23.9%, P=0.004). There was no evidence of differences in TDI, PI or HSI for those
with cancer vs non-cancer diagnoses (median TDI CRC 124 vs non-cancer 138 days,
P=0.142). First symptoms associated with shorter TDIs were rectal bleeding,
change in bowel habit, 'feeling different' and fatigue/tiredness. Anxiety,
depression and gastro-intestinal co-morbidities were associated with longer HSIs
and TDIs. Symptom duration-dependent effects were found for rectal bleeding and
change in bowel habit. CONCLUSIONS: Doctors and patients respond less promptly to
some symptoms of CRC than others. Healthcare professionals should be vigilant to
the possibility of CRC in patients with relevant symptoms and mental health or
gastro-intestinal comorbidities.
PMID- 27490804
TI - Genome-wide measures of DNA methylation in peripheral blood and the risk of
urothelial cell carcinoma: a prospective nested case-control study.
AB - BACKGROUND: Global DNA methylation has been reported to be associated with
urothelial cell carcinoma (UCC) by studies using blood samples collected at
diagnosis. Using the Illumina HumanMethylation450 assay, we derived genome-wide
measures of blood DNA methylation and assessed them for their prospective
association with UCC risk. METHODS: We used 439 case-control pairs from the
Melbourne Collaborative Cohort Study matched on age, sex, country of birth, DNA
sample type, and collection period. Conditional logistic regression was used to
compute odds ratios (OR) of UCC risk per s.d. of each genome-wide measure of DNA
methylation and 95% confidence intervals (CIs), adjusted for potential
confounders. We also investigated associations by disease subtype, sex, smoking,
and time since blood collection. RESULTS: The risk of superficial UCC was
decreased for individuals with higher levels of our genome-wide DNA methylation
measure (OR=0.71, 95% CI: 0.54-0.94; P=0.02). This association was particularly
strong for current smokers at sample collection (OR=0.47, 95% CI: 0.27-0.83).
Intermediate levels of our genome-wide measure were associated with decreased
risk of invasive UCC. Some variation was observed between UCC subtypes and the
location and regulatory function of the CpGs included in the genome-wide measures
of methylation. CONCLUSIONS: Higher levels of our genome-wide DNA methylation
measure were associated with decreased risk of superficial UCC and intermediate
levels were associated with reduced risk of invasive disease. These findings
require replication by other prospective studies.
PMID- 27490805
TI - The utility of urine-circulating miRNAs for detection of prostate cancer.
AB - BACKGROUND: In this paper, the utility of urine-circulating microRNAs (miRNAs) as
the potential biomarker of prostate cancer (PCa), the second most prevalent male
cancer worldwide, was evaluated. METHODS: Cancerous (N=56) and non-cancerous
(N=16) prostate tissues were analysed on TaqMan Low Density Array, with the
initial screening of 754 miRNAs in a subset of the samples. The abundance of
selected miRNAs was analysed in urine specimens from two independent cohorts of
patients with PCa (N=215 overall), benign prostatic hyperplasia (BPH; N=23), and
asymptomatic controls (ASC; N=62) by means of quantitative reverse transcription
PCR. RESULTS: Over 100 miRNAs were found deregulated in PCa as compared with non
cancerous prostate tissue. After thorough validation, four miRNAs were selected
for the analysis in urine specimens. The abundance of miR-148a and miR-375 in
urine was identified as specific biomarkers of PCa in both cohorts. Combined
analysis of urine-circulating miR-148a and miR-375 was highly sensitive and
specific for PCa in both cohorts (AUC=0.79 and 0.84) and strongly improved the
diagnostic power of the PSA test (AUC=0.85, cohort PCa1), including the grey
diagnostic zone (AUC=0.90). CONCLUSIONS: Quantitative measurement of urine
circulating miR-148a and miR-375 can serve as the non-invasive tool for sensitive
and specific detection of PCa.
PMID- 27490806
TI - Medical treatment of renal cancer: new horizons.
AB - Renal cell carcinoma (RCC) makes up 2-3% of adult cancers. The introduction of
tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors in
the mid-2000s radically changed the management of RCC. These targeted treatments
superseded immunotherapy with interleukin-2 and interferon. The pendulum now
appears to be shifting back towards immunotherapy, with the evidence of prolonged
overall survival of patients with metastatic RCC on treatment with the anti
programmed cell death 1 ligand monoclonal antibody, nivolumab. Clinical
prognostic criteria aid prediction of relapse risk for resected localised
disease. Unfortunately, for patients at high risk of relapse, no adjuvant
treatment has yet shown benefit, although further trials are yet to report.
Clinical prognostic models also have a role in the management of advanced
disease; now there is a pressing need for predictive biomarkers to direct
therapy. Treatment selection for metastatic disease is currently based on
histology, prognostic group and patient preference based on side effect profile.
In this article, we review the current medical and surgical management of
localised, oligometastatic and advanced RCC, including side effect management and
the evidence base for management of poor-risk and non-clear cell disease. We
discuss recent results from clinical trials and how these are likely to shape
future practice and a renaissance of immunotherapy for renal cell cancer.
PMID- 27490807
TI - Digital vs screen-film mammography in population-based breast cancer screening:
performance indicators and tumour characteristics of screen-detected and interval
cancers.
AB - BACKGROUND: Full-field digital mammography (FFDM) has replaced screen-film
mammography (SFM) in most breast cancer screening programs due to technological
advantages such as possibilities to adjust contrast, better image quality and
transfer capabilities. This study describes the performance indicators during the
transition from SFM to FFDM and the characteristics of screen-detected and
interval cancers. METHODS: Data of the Dutch breast cancer screening program,
region North from 2004 to 2010 were linked to The Netherlands Cancer Registry
(N=902 868). Performance indicators and tumour characteristics of screen-detected
and interval cancers were compared between FFDM and SFM. RESULTS: After initial
screens, recall rates were 2.1% (SFM) and 3.0% (FFDM; P<0.001). The positive
predictive values (PPV) were 25.6% (SFM) and 19.9% (FFDM; P=0.002). Detection
rates were similar, as were all performance indicators after subsequent screens.
Similar percentages of low-grade ductal carcinoma in situ (DCIS) were found for
SFM and FFDM. Invasive cancers diagnosed after subsequent screens with FFDM were
more often of high-grade (P=0.024) and ductal type (P=0.030). The incidence rates
of interval cancers were similar for SFM and FFDM after initial (2.69/1000 vs
2.51/1000; P=0.787) and subsequent screens (2.30 vs 2.41; P=0.652), with similar
tumour characteristics. CONCLUSIONS: FFDM resulted in similar rates of screen
detected and interval cancers, indicating that FFDM performs as well as SFM in a
breast cancer screening program. No signs of an increase in low-grade DCIS (which
might connote possible overdiagnosis) were seen. Nonetheless, after initial
screening, which accounts for 12% of all screens, FFDM resulted in higher recall
rate and lower PPV that requires attention.
PMID- 27490809
TI - Use of Hemostatic Agents in Hip and Knee Arthroplasty: A Critical Analysis
Review.
PMID- 27490810
TI - Treatment of Monteggia and Transolecranon Fracture-Dislocations of the Elbow: A
Critical Analysis Review.
PMID- 27490808
TI - Polyunsaturated fatty acids and prostate cancer risk: a Mendelian randomisation
analysis from the PRACTICAL consortium.
AB - BACKGROUND: Prostate cancer is a common cancer worldwide with no established
modifiable lifestyle factors to guide prevention. The associations between
polyunsaturated fatty acids (PUFAs) and prostate cancer risk have been
inconsistent. Using Mendelian randomisation, we evaluated associations between
PUFAs and prostate cancer risk. METHODS: We used individual-level data from a
consortium of 22 721 cases and 23 034 controls of European ancestry. Externally
weighted PUFA-specific polygenic risk scores (wPRSs), with explanatory variation
ranging from 0.65 to 33.07%, were constructed and used to evaluate associations
with prostate cancer risk per one standard deviation (s.d.) increase in
genetically-predicted plasma PUFA levels using multivariable-adjusted
unconditional logistic regression. RESULTS: No overall association was observed
between the genetically-predicted PUFAs evaluated in this study and prostate
cancer risk. However, risk reductions were observed for short-chain PUFAs,
linoleic (ORLA=0.95, 95%CI=0.92, 0.98) and alpha-linolenic acids (ORALA=0.96,
95%CI=0.93, 0.98), among men <62 years; whereas increased risk was found among
men ?62 years for LA (ORLA=1.04, 95%CI=1.01, 1.07). For long-chain PUFAs (i.e.,
arachidonic, eicosapentaenoic, and docosapentaenoic acids), increased risks were
observed among men <62 years (ORAA=1.05, 95%CI=1.02, 1.08; OREPA=1.04,
95%CI=1.01, 1.06; ORDPA=1.05, 95%CI=1.02, 1.08). CONCLUSION: Results from this
study suggest that circulating omega-3 and omega-6 PUFAs may have a different
role in the aetiology of early- and late-onset prostate cancer.
PMID- 27490811
TI - Hand Transplantation.
PMID- 27490812
TI - Pathogenesis of Adolescent Idiopathic Scoliosis.
PMID- 27490814
TI - "Smoking Does Not Go With Yoga:" A Qualitative Study of Women's Phenomenological
Perceptions During Yoga and Smoking Cessation.
AB - INTRODUCTION: Smoking cessation is often accompanied by withdrawal symptoms,
cigarette craving, increased negative affect, and increased experience of stress.
Because yoga has been shown to reduce stress and negative affect, it may be an
effective aid to smoking cessation. The objective of this study was to examine
women's phenomenological experiences of vinyasa yoga as part of a smoking
cessation program. METHODS: Focus groups were conducted post-intervention with
women (n = 20) who participated in a pilot randomized controlled trial of yoga as
a complementary therapy for smoking cessation. The 8-week vinyasa yoga
intervention included twice weekly 60-minute classes that involved breathing
exercises, postures (asanas), and relaxation techniques. Focus groups were audio
recorded and transcribed. Thematic analysis focused on descriptions of yoga,
breathing, and bodily sensations including cigarette craving. RESULTS: Focus
group participants described vinyasa yoga as physically challenging. Most
reported deliberate use of yogic breathing to cope with cigarette craving and
stress. Other perceived effects included relaxation and an increased sense of
body awareness and wellbeing. CONCLUSIONS: Participants viewed yoga as positive
and potentially helpful for quitting smoking. Yoga may be an effective adjunct
for smoking cessation.
PMID- 27490813
TI - Identification of Antigenic Proteins from Lichtheimia corymbifera for Farmer's
Lung Disease Diagnosis.
AB - The use of recombinant antigens has been shown to improve both the sensitivity
and the standardization of the serological diagnosis of Farmer's lung disease
(FLD). The aim of this study was to complete the panel of recombinant antigens
available for FLD serodiagnosis with antigens of Lichtheimia corymbifera, known
to be involved in FLD. L. corymbifera proteins were thus separated by 2D
electrophoresis and subjected to western blotting with sera from 7 patients with
FLD and 9 healthy exposed controls (HEC). FLD-associated immunoreactive proteins
were identified by mass spectrometry based on a protein database specifically
created for this study and subsequently produced as recombinant antigens. The
ability of recombinant antigens to discriminate patients with FLD from controls
was assessed by ELISA performed with sera from FLD patients (n = 41) and controls
(n = 43) recruited from five university hospital pneumology departments of France
and Switzerland. Forty-one FLD-associated immunoreactive proteins from L.
corymbifera were identified. Six of them were produced as recombinant antigens.
With a sensitivity and specificity of 81.4 and 77.3% respectively, dihydrolipoyl
dehydrogenase was the most effective antigen for discriminating FLD patients from
HEC. ELISA performed with the putative proteasome subunit alpha type as an
antigen was especially specific (88.6%) and could thus be used for FLD
confirmation. The production of recombinant antigens from L. corymbifera
represents an additional step towards the development of a standardized ELISA kit
for FLD diagnosis.
PMID- 27490815
TI - Oyster's cells regulatory volume decrease: A new tool for evaluating the toxicity
of low concentration hydrocarbons in marine waters.
AB - Human activities require fossil fuels for transport and energy, a substantial
part of which can accidentally or voluntarily (oil spillage) flow to the marine
environment and cause adverse effects in human and ecosystems' health. This
experiment was designed to estimate the suitability of an original cellular
biomarker to early quantify the biological risk associated to hydrocarbons
pollutants in seawater. Oocytes and hepatopancreas cells, isolated from oyster
(Crassostrea gigas), were tested for their capacity to regulate their volume
following a hypo-osmotic challenge. Cell volumes were estimated from cell images
recorded at regular time intervals during a 90min-period. When exposed to diluted
seawater (osmolalities from 895 to 712mosmkg(-1)), both cell types first swell
and then undergo a shrinkage known as Regulatory Volume Decrease (RVD). This
process is inversely proportional to the magnitude of the osmotic shock and is
best fitted using a first-order exponential decay model. The Recovered Volume
Factor (RVF) calculated from this model appears to be an accurate tool to compare
cells responses. As shown by an about 50% decrease in RVF, the RVD process was
significantly inhibited in cells sampled from oysters previously exposed to a low
concentration of diesel oil (8.4mgL(-1) during 24h). This toxic effect was
interpreted as a decreased permeability of the cell membranes resulting from an
alteration of their lipidic structure by diesel oil compounds. In contrast, the
previous contact of oysters with diesel did not induce any rise in the gills
glutathione S-transferase specific activity. Therefore, this work demonstrates
that the study of the RVD process of cells selected from sentinel animal species
could be an alternative bioassay for the monitoring of hydrocarbons and probably,
of various chemicals in the environment liable to alter the cellular regulations.
Especially, given the high sensitivity of this biomarker compared with a proven
one, it could become a relevant and accurate tool to estimate the biological
hazards of micropollutants in the water.
PMID- 27490817
TI - Effect of bike-fit in the perception of comfort, fatigue and pain.
AB - The aim of this study was to assess the influence of different bike positions on
the perception of fatigue, pain and comfort. Twenty cyclists underwent three
tests that involved cycling for 45 min at their individual 50% peak aerobic power
output while adopting different positions on the bike. Participants performed the
cycling tests adopting three positions defined by two parameters (knee flexion
angle [20 degrees , 30 degrees , 40 degrees ] and trunk flexion angle [35 degrees
, 45 degrees , 55 degrees ]) in random order. Angles were measured using a 2D
motion analysis system during cycling and applying Fonda's correction factor.
Perceptions of comfort, fatigue and pain were reported before the end of each
test. The combination of 40 degrees knee flexion and 35 degrees trunk flexion
was perceived as the most uncomfortable position. Moreover, greater knee flexion
had a negative effect on trunk comfort, accompanied by greater levels of fatigue
and pain perception in the anterior part of the thigh and knee. In conclusion,
cyclists perceived the most comfortable position to be when the saddle height was
within the recommended knee angle (30 degrees calculated from the offset
position or 40 +/- 4.0 degrees of absolute value). Upright trunk was found to be
the most comfortable position for recreational cyclists, where aerodynamics is
not so important. Cyclists' bike perceptions should be taken into account when it
comes to choosing the most beneficial position, since this can play a role in
injury prevention and enhance cycling performance.
PMID- 27490816
TI - Post-Decision Wagering Affects Metacognitive Awareness of Emotional Stimuli: An
Event Related Potential Study.
AB - The present research investigated metacognitive awareness of emotional stimuli
and its psychophysiological correlates. We used a backward masking task
presenting participants with fearful or neutral faces. We asked participants for
face discrimination and then probed their metacognitive awareness with confidence
rating (CR) and post-decision wagering (PDW) scales. We also analysed
psychophysiological correlates of awareness with event-related potential (ERP)
components: P1, N170, early posterior negativity (EPN), and P3. We have not
observed any differences between PDW and CR conditions in the emotion
identification task. However, the "aware" ratings were associated with increased
accuracy performance. This effect was more pronounced in PDW, especially for
fearful faces, suggesting that emotional stimuli awareness may be enhanced by
monetary incentives. EEG analysis showed larger N170, EPN and P3 amplitudes in
aware compared to unaware trials. It also appeared that both EPN and P3 ERP
components were more pronounced in the PDW condition, especially when emotional
faces were presented. Taken together, our ERP findings suggest that metacognitive
awareness of emotional stimuli depends on the effectiveness of both early and
late visual information processing. Our study also indicates that awareness of
emotional stimuli can be enhanced by the motivation induced by wagering.
PMID- 27490819
TI - Effects of Dual-Energy Technique on Radiation Exposure and Image Quality in
Pediatric Body CT.
AB - OBJECTIVE: The purpose of this study was to assess the effects of dual-energy CT
(DECT) on radiation exposure and image quality in pediatric body CT. MATERIALS
AND METHODS: This retrospective study included 79 children (median age, 10.1
years; range, 12 days-18 years) who underwent thoracic or abdominal-pelvic CT or
CT angiography with dual-energy technique between October 2014 and March 2015.
The delivered volume CT dose index (CTDIvol) from DECT was recorded and compared
with the estimated CTDIvol had the patient undergone scanning with a standard
single-energy CT (SECT) protocol. Size-specific dose estimates were calculated
for both DECT and SECT. Image quality was subjectively scored (scale, 1-4). For
16 of 79 patients who underwent both DECT and SECT, image contrast and noise were
measured and contrast-to-noise ratio calculated. Parametric and nonparametric
testing of independent and paired samples was performed. RESULTS: For all 79
studies, actual median CTDIvol and size-specific dose estimate were 3.7 and 5.9
mGy for DECT versus prescanning estimates of 4.4 and 7.7 mGy for SECT, resulting
in 12.5% and 11.2% radiation exposure reduction (p < 0.01). Diagnostic image
quality was achieved in all patients. In the 16-patient subset, the median
CTDIvol values of DECT and SECT were 3.1 and 3.4 mGy (p < 0.05). Median noise was
greater with DECT than with SECT (p < 0.01), but the mean contrast-to-noise
ratios for the liver and portal vein were similar (liver, p = 0.32; portal vein,
p = 0.21). CONCLUSION: In pediatric body CT, the use of DECT results in radiation
exposures comparable to or less than those of SECT while maintaining contrast and
contrast-to-noise ratio.
PMID- 27490818
TI - Branched-Chain Amino Acids as New Biomarkers of Major Depression - A Novel
Neurobiology of Mood Disorder.
AB - BACKGROUND: The proteinogenic branched-chain amino acids (BCAAs) valine, leucine
and isoleucine might play an unrecognised crucial role in the development of
depression through their activation of the mammalian target of rapamycin (mTor)
pathway. The aim of this research project is to evaluate whether BCAAs are
altered in patients with major depression and might thus be appropriate
biomarkers for major depression. METHODS: The concentrations of valine, leucine
and isoleucine were determined in 71 in-patients with major depression and 48
healthy controls by high-pressure liquid chromatography. Psychiatric and
laboratory assessments were obtained at the time of in-patient admittance.
RESULTS: The BCAAs are significantly decreased in patients with major depression
in comparison with healthy subjects (valine: Mann-Whitney-U: 968.0; p <0.0001,
leucine: Mann-Whitney-U: 1246.5; p = 0.013, isoleucine: Mann-Whitney-U: 1252.5; p
= 0.014). Furthermore, as shown by Spearman's rank correlation coefficients,
there is a significant negative correlation between valine, leucine and
isoleucine concentrations and the Hamilton Depression Rating Scale (HAMD-17) as
well as Beck Depression Inventory (BDI-II) scores. CONCLUSIONS: Our study results
are strong evidence that in patients with major depression, BCAAs might be
appropriate biomarkers for depression. Reduced activation of the mammalian target
of rapamycin (mTor) due to a reduction of BCAAs might play a crucial unrecognised
factor in the etiology of depression and may evoke depressive symptomatology and
lower energy metabolism in patients with major depression. In the future, mTor
and its up- and downstream signalling partners might be important targets for the
development of novel antidepressants.
PMID- 27490821
TI - Arylboration of 1-Arylalkenes by Cooperative Nickel/Copper Catalysis.
AB - A method for the arylboration of 1-arylalkenes with bis(pinacolato)diboron and
aryl chlorides or tosylates by cooperative Ni/Cu catalysis has been developed,
which affords 2-boryl-1,1-diarylalkanes in high regio- and stereoselectivity.
Under the applied conditions, this method is tolerant toward various functional
groups, including silyl ether, alkoxycarbonyl, and aminocarbonyl moieties.
PMID- 27490820
TI - Linking Genes and Brain Development of Honeybee Workers: A Whole-Transcriptome
Approach.
AB - Honeybees live in complex societies whose capabilities far exceed those of the
sum of their single members. This social synergism is achieved mainly by the
worker bees, which form a female caste. The worker bees display diverse
collaborative behaviors and engage in different behavioral tasks, which are
controlled by the central nervous system (CNS). The development of the worker
brain is determined by the female sex and the worker caste determination signal.
Here, we report on genes that are controlled by sex or by caste during
differentiation of the worker's pupal brain. We sequenced and compared
transcriptomes from the pupal brains of honeybee workers, queens and drones. We
detected 333 genes that are differently expressed and 519 genes that are
differentially spliced between the sexes, and 1760 genes that are differentially
expressed and 692 genes that are differentially spliced between castes. We
further found that 403 genes are differentially regulated by both the sex and
caste signals, providing evidence of the integration of both signals through
differential gene regulation. In this gene set, we found that the molecular
processes of restructuring the cell shape and cell-to-cell signaling are
overrepresented. Our approach identified candidate genes that may be involved in
brain differentiation that ensures the various social worker behaviors.
PMID- 27490822
TI - Wnt signal transduction pathways: modules, development and evolution.
AB - BACKGROUND: Wnt signal transduction pathway (Wnt STP) is a crucial intracellular
pathway mainly due to its participation in important biological processes,
functions, and diseases, i.e., embryonic development, stem-cell management, and
human cancers among others. This is why Wnt STP is one of the highest researched
signal transduction pathways. Study and analysis of its origin, expansion and
gradual development to the present state as found in humans is one aspect of Wnt
research. The pattern of development and evolution of the Wnt STP among various
species is not clear till date. A phylogenetic tree created from Wnt STPs of
multiple species may address this issue. RESULTS: In this respect, we construct a
phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the
'Module Tree'. A module is nothing but a self-sufficient minimally-dependent
subset of the original Wnt STP. Authenticity of the module tree is tested by
comparing it with the two reference trees. CONCLUSIONS: The module tree performs
better than an alternative phylogenetic tree constructed from pathway topology of
Wnt STPs. Moreover, an evolutionary emergence pattern of the Wnt gene family is
created and the module tree is tallied with it to showcase the significant
resemblances.
PMID- 27490823
TI - Comparison of Ai Chi and Impairment-Based Aquatic Therapy for Older Adults With
Balance Problems: A Clinical Study.
AB - BACKGROUND AND PURPOSE: Older adults with balance deficits often fear falling and
limit their mobility. Poor balance is multifactorial, influenced by medication
interactions, musculoskeletal and sensory system changes, and poor neuromuscular
response to changes in body positions. Aquatic physical therapy (APT) is an
intervention used to improve balance and decrease falls. Ai Chi is a water-based
exercise program. It incorporates slow movements of progressive difficulty
utilizing the upper and lower extremities and trunk coordinated with deep
breathing. It is used for relaxation, strengthening, and balance training. The
purpose of this study was to determine whether Ai Chi provides better results
than conventional impairment-based aquatic therapy (IBAT) for older adults with
balance deficits. METHODS: Thirty-two community-dwelling adults, 65 to 85 years
old, were referred to 2 different community pools for APT. Fifteen participants
received Ai Chi-based aquatic interventions and 17 participants received an IBAT
program. Physical therapists trained in both programs completed interventions and
determined discharge. Physical balance measures, which included the Berg Balance
Scale (BBS) and Timed Up and Go (TUG), were collected pre- and posttherapy. Self
reported outcome measures, the Activities-Specific Balance Confidence Scale (ABC)
and Numerical Pain Rating Scale (NPRS), were collected pre- and posttherapy and 3
and 6-month postdischarge. RESULTS: A 2-way (group by time) mixed-model analysis
of covariance with initial outcome scores as a covariate revealed no difference
between groups in any of the outcome measures (BBS, P = .53; TUG, P = .39; ABC, P
= .63; NPRS, P = .27). Repeated-measures analysis and dependent t tests showed
significant improvements in the BBS (P = .00) and TUG (P = .03) after APT. The
ABC and NPRS did not improve significantly (ABC, P = .27; NPRS, P = .77).
CONCLUSIONS: There were no significant differences found in balance measures,
balance confidence, or pain levels for community-dwelling older adults between
the Ai Chi and IBAT programs. Physical outcome measures improved with APT but
patient-reported measures did not. Further study is indicated to determine the
most effective treatment frequency and duration for this population.
PMID- 27490824
TI - On Sublimation.
AB - Although it encapsulates the Freudian theory of art, the theory of sublimation
has become outmoded. What is more, since its inception there has always been
something ill-defined about it. Does it use sexualized or de-sexualized drive
energy? Is it a defence or an alternative to defence? Does it serve Eros or
Thanatos? Is it useful in clinical work or is it unusable? The only, albeit
uncertain, aid to a definition relies on the extrinsic criterion of concrete
artistic realization. My aim here to revisit and possibly 'reinvent' sublimation
in the light of certain principles of the pre-Romantic aesthetics of the sublime.
Both are theories of spiritual elevation, in other words, elevation that moves
towards abstract thinking, and of man's 'moral' achievement; and both attempt to
explain the mystery of aesthetic experience. On the one hand, the aesthetics of
the sublime offers a modern myth that helps us articulate a series of factors
occasionally referred to by various authors as constitutive of sublimation but
which have not been incorporated into a single organic framework: loss and early
mourning work; the earlier existence of a catastrophic factor - to be regarded,
depending on the situation, as either traumatic or simply 'negative'; the
correspondence with a process of somatopsychic categorization which coincides
with subjectivity. On the other hand, it also helps us grasp the experience of
negative pleasure empathically, living it 'from the inside'.
PMID- 27490826
TI - Identification and characterization of the missing phosphatase on the riboflavin
biosynthesis pathway in Arabidopsis thaliana.
AB - Despite the importance of riboflavin as the direct precursor of the cofactors
flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), the
physiologically relevant catalyst dephosphorylating the riboflavin biosynthesis
pathway intermediate 5-amino-6-ribitylamino-2,4(1H,3H) pyrimidinedione 5'
phosphate (ARPP) has not been characterized from any organism. By using as the
query sequence a previously identified plastidial FMN hydrolase AtcpFHy1
(At1g79790), belonging to the haloacid dehalogenase (HAD) superfamily, seven
candidates for the missing ARPP phosphatase were found, cloned, recombinantly
expressed, and purified. Activity screening showed that the enzymes encoded by
AtcpFHy1, At4g11570, and At4g25840 catalyze dephosphorylation of ARPP. AtcpFHy1
was renamed AtcpFHy/PyrP1, At4g11570 and At4g25840 were named AtPyrP2 and
AtGpp1/PyrP3, respectively. Subcellular localization in planta indicated that
AtPyrP2 was localized in plastids and AtGpp1/PyrP3 in mitochondria. Biochemical
characterization of AtcpFHy/PyrP1 and AtPyrP2 showed that they have similar Km
values for the substrate ARPP, with AtcpFHy/PyrP1 having higher catalytic
efficiency. Screening of 21 phosphorylated substrates showed that AtPyrP2 is
specific for ARPP. Molecular weights of AtcpFHy/PyrP1 and AtPyrP2 were estimated
at 46 and 72 kDa, suggesting dimers. pH and temperature optima for AtcpFHy/PyrP1
and AtPyrP2 were ~7.0-8.5 and 40-50 degrees C. T-DNA knockout of AtcpFHy/PyrP1
did not affect the flavin profile of the transgenic plants, whereas silencing of
AtPyrP2 decreased accumulation of riboflavin, FMN, and FAD. Our results strongly
support AtPyrP2 as the missing phosphatase on the riboflavin biosynthesis pathway
in Arabidopsis thaliana. The identification of this enzyme closes a long-standing
gap in understanding of the riboflavin biosynthesis in plants.
PMID- 27490825
TI - In-Cell Enzymology To Probe His-Heme Ligation in Heme Oxygenase Catalysis.
AB - Heme oxygenase (HO) is a ubiquitous enzyme with key roles in inflammation, cell
signaling, heme disposal, and iron acquisition. HO catalyzes the oxidative
conversion of heme to biliverdin (BV) using a conserved histidine to coordinate
the iron atom of bound heme. This His-heme interaction has been regarded as being
essential for enzyme activity, because His-to-Ala mutants fail to convert heme to
biliverdin in vitro. We probed a panel of proximal His mutants of cyanobacterial,
human, and plant HO enzymes using a live-cell activity assay based on
heterologous co-expression in Escherichia coli of each HO mutant and a
fluorescent biliverdin biosensor. In contrast to in vitro studies with purified
proteins, we observed that multiple HO mutants retained significant activity
within the intracellular environment of bacteria. X-ray crystallographic
structures of human HO1 H25R with bound heme and additional functional studies
suggest that HO mutant activity inside these cells does not involve heme ligation
by a proximal amino acid. Our study reveals unexpected plasticity in the active
site binding interactions with heme that can support HO activity within cells,
suggests important contributions by the surrounding active site environment to HO
catalysis, and can guide efforts to understand the evolution and divergence of HO
function.
PMID- 27490828
TI - Molecular dynamics techniques for modeling G protein-coupled receptors.
AB - G protein-coupled receptors (GPCRs) constitute a major class of drug targets and
modulating their signaling can produce a wide range of pharmacological outcomes.
With the growing number of high-resolution GPCR crystal structures, we have the
unprecedented opportunity to leverage structure-based drug design techniques.
Here, we discuss a number of advanced molecular dynamics (MD) techniques that
have been applied to GPCRs, including long time scale simulations, enhanced
sampling techniques, water network analyses, and free energy approaches to
determine relative binding free energies. On the basis of the many success
stories, including those highlighted here, we expect that MD techniques will be
increasingly applied to aid in structure-based drug design and lead optimization
for GPCRs.
PMID- 27490827
TI - Discovery and Preclinical Characterization of 6-Chloro-5-[4-(1
hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic Acid (PF-06409577), a Direct
Activator of Adenosine Monophosphate-activated Protein Kinase (AMPK), for the
Potential Treatment of Diabetic Nephropathy.
AB - Adenosine monophosphate-activated protein kinase (AMPK) is a protein kinase
involved in maintaining energy homeostasis within cells. On the basis of human
genetic association data, AMPK activators were pursued for the treatment of
diabetic nephropathy. Identification of an indazole amide high throughput
screening (HTS) hit followed by truncation to its minimal pharmacophore provided
an indazole acid lead compound. Optimization of the core and aryl appendage
improved oral absorption and culminated in the identification of indole acid, PF
06409577 (7). Compound 7 was advanced to first-in-human trials for the treatment
of diabetic nephropathy.
PMID- 27490830
TI - The confusion of psychiatric comorbidity.
PMID- 27490829
TI - Preoperative Predictors in Chronic Suppurative Otitis Media for Ossicular Chain
Discontinuity: A Cross-Sectional Study.
AB - OBJECTIVE: Ossicular discontinuity may result from chronic suppurative otitis
media and is usually detected intraoperatively. Our objective is to determine
whether a preoperative audiogram can preoperatively predict the presence or
absence of ossicular discontinuity. METHODS: A cross-sectional study was
prospectively run on our patients, aged 12-75 years, ultimately operated on for
chronic suppurative otitis media. Preoperative audiograms were analyzed to
measure frequency-specific air-bone gap (ABG) cutoff values. Intraoperatively,
ossicular chain integrity was carefully checked. Logistic regression analysis was
done to obtain a predictive model. RESULTS: A total of 270 patients (306 ears)
were included. Frequency-specific ABG cutoff values can predict ossicular
discontinuity, namely: high ABGs at 1,000 Hz (>27.5 dB) and 2,000 Hz (>17.5 dB)
are the most reliable variables associated with ossicular discontinuity.
CONCLUSION: Preoperative audiograms can predict the presence of ossicular
discontinuity in chronic suppurative otitis media. Large ABGs at both 1,000 and
2,000 Hz can predict ossicular discontinuity with a great degree of certainty.
PMID- 27490831
TI - Efficacy of stimulants for psychiatric symptoms in individuals with traumatic
brain injury.
AB - BACKGROUND: The objective of this systematic review is to summarize data from
published randomized controlled trials (RCTs) on the efficacy of stimulants for
psychiatric symptoms in individuals with traumatic brain injury (TBI). METHODS: A
literature search was conducted of 5 major databases (PubMed, MEDLINE, PsycINFO,
Embase, and Cochrane Collaboration) that identified RCTs on the use of stimulants
for human patients with a diagnosis of TBI. RESULTS: A total of 176 articles were
identified, of which 18 matched the inclusion criteria and were reviewed in their
entirety. The majority (17) of studies assessed methylphenidate (MPH), 1 assessed
dextroamphetamine and MPH, and 1 assessed modafinil. One study showed significant
improvement in depressive symptoms with MPH. Seven studies showed significant
improvement in reaction time, whereas 4 studies showed significant improvement in
accuracy with MPH compared with placebo. Of the 2 studies that included follow
up, only 1 found significant differences in disability ratings, attention
concentration, and motor memory at 30 days but not 90 days between the stimulant
and placebo groups. The majority of studies demonstrated significant treatment
effects immediately (ie, within minutes to hours) after first-time stimulant
administration. Five of the 18 studies (3 adult, 2 pediatric) did not find
benefit for stimulants when compared with placebo. Two studies that evaluated
self-reported side effects found no significant difference between treatment
groups, although 1 study showed a significant increase in mean arterial pressure
in the stimulant group. CONCLUSIONS: There is limited evidence to suggest
efficacy of stimulants for psychiatric symptoms in individuals with TBI. However,
stimulants appear to improve attention after first-time administration and for
short time periods in these individuals.
PMID- 27490832
TI - Longitudinal assessment of clinical risk factors for depression in schizophrenia
spectrum disorders.
AB - BACKGROUND: During initial assessment of individuals with schizophrenia and
related disorders (schizophrenia spectrum disorders [SSDs]), clinicians tend to
pay greater attention to psychotic symptoms than mood symptoms, including
depression. Depression is reported to influence the course of SSDs, but not much
is known about the risk factors for depression in SSDs. In the present study, we
examined clinical predictors of depression in SSDs. METHODS: The sample included
71 patients with SSDs followed in a modified Assertive Community Treatment
program, the Community Support Network of Springfield, Illinois. The study design
was naturalistic, prospective, and longitudinal (mean follow-up = 8.3 years; SD =
7.3). The GENMOD procedure appropriate for repeated measures analysis with
dichotomous outcome variables followed longitudinally was computed. RESULTS:
Rates of depression ranged from 18% to 41% over the differing assessment periods.
Schizophrenia and schizoaffective disorder did not vary by depression rate.
Depression independent of SSD diagnosis was associated with greater
hospitalization rates. Clinical variables predict- ing depression were auditory
hallucinations, delusions, poor insight, and poor judgment. CONCLUSIONS:
Psychotic symptoms in the course of SSDs are risk factors for depression. As a
consequence, the mental status examination of patients with SSDs with active
psychosis should include assessment of mood changes. Further research is
warranted to determine if treatment of depression among patients with SSDs may
reduce their rates of hospitalization.
PMID- 27490833
TI - Does comorbidity matter in body-focused repetitive behavior disorders?
AB - BACKGROUND: Trichotillomania (TTM) and skin-picking disorder (SPD) have been
characterized as body-focused repetitive behavior disorders (BFRBs). Because
BFRBs frequently co-occur, we sought to discover the similarities and differences
for individuals having both TTM and SPD as opposed to 1 of these disorders.
METHODS: Participants with primary TTM (N = 421) were evaluated regarding the
comorbidity of SPD, and participants with primary SPD (N = 124) were evaluated
regarding the comorbidity of TTM. The effects of comorbidity overlap on
demographic and clinical measures were evaluated. RESULTS: Of the 421
participants with primary TTM, 61 (14.5%) had co-occurring SPD. Of 124
participants with primary SPD, 21 (16.9%) had comorbid TTM. Participants with
primary TTM and comorbid SPD had significantly more severe trichotillomania
symptoms and were more likely to have major depressive disorder than those with
TTM alone. Participants with primary SPD and comorbid TTM reported significantly
more severe skin-picking symptoms than those who had only SPD. CONCLUSIONS:
Individuals with co-occurring TTM and SPD may have more problematic symptoms with
the primary repetitive behavior. Hair pullers with comorbid SPD were more likely
to have comorbid depression. Evaluating patients for multiple BFRBs may be
important to assess the severity of symptoms and may have treatment implications.
PMID- 27490834
TI - Expanded conceptualization of multimorbidity to encompass substance use disorders
and other psychiatric illness.
AB - BACKGROUND: Traditionally, the study of medicine has focused on individual
diseases. In reality, however, diseases tend to co-occur in individual patients,
a concept known as multimorbidity. Multimorbidity most often is seen in geriatric
practice. Empirical data on patients with multiple chronic disorders and clinical
care guidelines based on single conditions are insufficient to inform medical
care of patients with >1 medical condition. METHODS: This article reviews
concepts of multimorbidity in the published literature in the context of
substance use disorders, other psychiatric disorders, and associated social and
environmental problems in other populations, including public sector service
populations. RESULTS: Besides historically recognized co-occurrence of 3
dimensions of illness, including multiple medical illnesses, psychiatric
disorders, and substance use disorders in varying combinations with one another,
a fourth dimension of multimorbidity that includes associated social and
environmental conditions fits within this construction. CONCLUSIONS: Additional
steps are needed to address more effectively the needs of patients with substance
use and other psychiatric disorders in the public sector psychiatric systems of
care. These efforts will need to address the systems theory approach to
multimorbidity that entails the socioeconomic and environmental aspects of their
conditions.
PMID- 27490835
TI - Placebo-controlled augmentation trials of the antioxidant NAC in schizophrenia: A
review.
AB - BACKGROUND: Several studies have reported that schizophrenia is associated with
mitochondrial abnormalities, glutathione deficit, and increased brain oxidative
stress (free radicals). N-acetylcysteine (NAC) is a strong antioxidant with
potential therapeutic benefit in schizophrenia, according to some reports. We
conducted a review of the published controlled studies, with the goal of
determining the efficacy profile of NAC as an adjunctive treatment for
schizophrenia. METHODS: An online search was conducted for all placebo
controlled, double-blind, randomized clinical trials of NAC in schizophrenia, and
a review was conducted. RESULTS: Two studies met the criteria for inclusion. Berk
et al (2008) used NAC as an adjunctive treatment to atypical antipsychotics in
subjects with chronic schizophrenia who were stable on antipsychotic medications.
Treatment at 8 weeks was less efficacious than placebo, but at 24 weeks produced
significant reductions vs placebo in Positive and Negative Syndrome Scale (PANSS)
negative (d = 0.52), general (d = 0.46), and total (d = 0.57) scores. Farokhnia
et al (2013) used NAC as an adjunctive treatment to risperidone in subjects with
chronic schizophrenia who were experiencing an acute exacerbation episode. Eight
weeks of treatment led to clinically significant reductions vs placebo in PANSS
negative (d = 0.96), general (d = 0.59), and total (d = 0.88) scores.
CONCLUSIONS: The data suggest that adjunctive NAC may be efficacious in reducing
negative and general symptoms in schizophrenia.
PMID- 27490836
TI - The evolution of PTSD criteria across editions of DSM.
AB - BACKGROUND: The diagnosis of posttraumatic stress disorder (PTSD) has remained
controversial from the time of its first inclusion in DSM-III. No reviews have
fully documented the shifting PTSD definitions across editions of the criteria.
This article chronicles the evolution of PTSD across editions of the DSM.
METHODS: Diagnostic precursors to PTSD in DSM-I and DSM-II were briefly
described, followed by systematic review of PTSD in subsequent editions of the
DSM. Sections of the criteria and accompanying text were sorted into tables
permitting visual comparisons across the editions. Research findings related to
specific changes in the editions were provided from available research literature
identified through specific PubMed searches using keywords relevant to each
specific change. RESULTS: Fundamental topics of debate identified in this review
are validity of the diagnosis, the trauma criterion, the role of symptoms in
defining its psychopathology, differentiation from other disorders, and
specifiers such as delayed onset. CONCLUSIONS: DSM-5 has corrected several major
ambiguities and errors of the former editions that are fundamental to the
construct of PTSD as a disorder that is defined conditionally in relation to
exposure to trauma, but problems remain in DSM-5 trauma criteria, especially
inconsistencies between exposure criteria and the definition of trauma.
Discerning the critical distinctions required to understand PTSD depends on
underlying clarity in terminology and precision in application of the diagnosis
by academicians and clinicians. Trauma must be differentiated from other kinds of
stressful events and conceptualized as an incident defined by physical injury
rather than by emotional response.
PMID- 27490837
TI - Anxiety or agitation in mood disorder with mixed features: A review with a focus
on validity as a dimensional criterion.
AB - BACKGROUND: The diagnostic validity of mixed features, excluding anxiety or
psychomotor agitation in mood disorders, has not yet been fully examined. METHOD:
PubMed and relevant English-language literature (regardless of year) were
searched. Keywords were mixed or mixed state or mixed features or mixed episode
and anxious or anxiety or agitation and bipolar disorder or depressive disorder
or mood disorder or affective disorder. RESULTS: Most studies on anxiety or
psychomotor agitation have included a significant correlation relevant to the
"with mixed features" specifier, although it is common in both poles of mood
episodes regardless of the predominant polarity. There is some confusion between
the characteristic of classical mixed states and the definition of the mixed
features specifier with the newly added anxious distress specifier in DSM-5,
specifically, whether to include anxiety and agitation as significant
characteristics. This change is of concern because a large proportion of patients
with mixed features are now unspecified, and this may influence treatment
planning and prognosis. CONCLUSIONS: The findings of our review suggest that
anxiety and psychomotor agitation can be core symptoms in mood episodes with
mixed features and important clinical clues for prediction of treatment effects
and disease course.
PMID- 27490838
TI - DSM-5-defined attenuated psychosis syndrome and conversion to full-scale
schizophrenia spectrum disorders: An institution-wide retrospective review.
AB - BACKGROUND: The objective of the study was to determine if DSM-5-defined
attenuated psychosis syndrome (APS) could identify individuals with prodromal
psychosis and predict conversion to schizophrenia spectrum disorders at a rate
similar to that observed in previous studies that utilized structured interviews
and specialized rating scales. METHODS: A retrospective review of patients'
medical records was used to identify individuals meeting diagnostic criteria for
the APS, followed by further evaluation 2 to 3 years after the initial diagnosis,
to determine if they converted to schizophrenia spectrum disorders. Results then
were compared with previous studies. RESULTS: Of our study population, 43.4%
converted to schizophrenia or schizoaffective disorder 2 to 3 years after initial
diagnosis of APS. Comparison at the 3-year mark indicated that there was no
significant difference between our observed rates and previously published
conversion rates (P = .066). Three covariates were found to increase
significantly the rates of conversion when added to the APS criteria: Cannabis
use (P = .048), lack of previous Axis I diagnosis (P = .005), and lack of
previous treatment with psychotropic medications (P = .009). CONCLUSIONS: APS
accurately predicts conversion to full-scale schizophrenia spectrum disorders at
a rate similar to that observed in previous studies using structured interviews
and specialized rating scales.
PMID- 27490839
TI - Diagnosis Accuracy of Transcutaneous Bilirubinometry in Very Preterm Newborns.
AB - BACKGROUND: Transcutaneous bilirubin (TcB) is a validated test for systematic
screening of neonatal hyperbilirubinemia and monitoring term and near-term
infants under phototherapy. OBJECTIVES: To evaluate TcB diagnostic accuracy for
very preterm neonates. METHODS: Total serum bilirubin (TSB) and TcB measurements
were performed prospectively in a multicenter sample of newborns <30 weeks of
gestational age (GA). TcB sensitivity, specificity, predictive values, and
likelihood ratios for the detection of neonates requiring phototherapy were
calculated over the first 15 days of life, with or without phototherapy, with the
expectation of achieving a detection rate of hyperbilirubinemia of over 95%. The
potential influence of neonatal characteristics on the discordance between TcB
and TSB in very preterm newborns was analyzed using multivariate multilevel
logistic regression analyses. RESULTS: Altogether, 481 measurements were analyzed
in 167 preterm patients. Mean GA was 27.6 +/- 1.6 weeks. The rates of newborns
requiring phototherapy were 52% in the first 3 days, 16% from the 4th to the 7th
day, and 2% during the second week. Diagnostic performance was similar among
babies with or without phototherapy. TcB sensitivity decreased over time from
100% (93.9-100.0) to 50% (1.3-98.7). Specificity showed an inverse evolution from
14.8% (7.0-26.2) to 80.7% (72.2-89.2). The best performance was that of negative
predictive values which varied from 95.5 to 100.0. False negatives were rare
throughout the study (0.8% of measurements). In a multivariate analysis, the only
factor significantly influencing discordance between TcB and TSB was postnatal
age. We did not find any impact of GA and skin color. CONCLUSION: Among very
preterm babies, TcB measurements might be useful for screening for neonatal
jaundice in the first 2 weeks of life. In case of a TcB value below the
phototherapy threshold, invasive TSB quantification could be unnecessary, with
potential avoidance of blood drawing.
PMID- 27490840
TI - Click-Dimerized Cinchona Alkaloids.
AB - A series of Cinchona alkaloid-derived dimers were obtained in high yields in
copper-catalyzed 1,3-dipolar "click" cycloaddition using bis(TMS)butadiyne and
other bivalent alkynes. The products with bitriazole linkers were effective
ligands for asymmetric copper-catalyzed Michael addition. It was shown that the
presence of such linker was responsible for effective chirality transfer.
PMID- 27490842
TI - Probabilistic evaluation of n traces with no putative source: A likelihood ratio
based approach in an investigative framework.
AB - Analysis of marks recovered from different crime scenes can be useful to detect a
linkage between criminal cases, even though a putative source for the recovered
traces is not available. This particular circumstance is often encountered in the
early stage of investigations and thus, the evaluation of evidence association
may provide useful information for the investigators. This association is
evaluated here from a probabilistic point of view: a likelihood ratio based
approach is suggested in order to quantify the strength of the evidence of trace
association in the light of two mutually exclusive propositions, namely that the
n traces come from a common source or from an unspecified number of sources. To
deal with this kind of problem, probabilistic graphical models are used, in form
of Bayesian networks and object-oriented Bayesian networks, allowing users to
intuitively handle with uncertainty related to the inferential problem.
PMID- 27490841
TI - What are the appropriate indicators of surgical difficulty during laparoscopic
cholecystectomy? Results from a Japan-Korea-Taiwan multinational survey.
AB - BACKGROUND: Serious complications continue to occur in laparoscopic
cholecystectomy (LC). The commonly used indicators of surgical difficulty such as
the duration of surgery are insufficient because they are surgeon and institution
dependent. We aimed to identify appropriate indicators of surgical difficulty
during LC. METHODS: A total of 26 Japanese expert LC surgeons discussed using the
nominal group technique (NGT) to generate a list of intraoperative findings that
contribute to surgical difficulty. Thereafter, a survey was circulated to 61
experts in Japan, Korea, and Taiwan. The questionnaire addressed LC experience,
surgical strategy, and perceptions of 30 intraoperative findings listed by the
NGT. RESULTS: The response rate of the survey was 100%. There was a statistically
significant difference among nations regarding the duration of surgery and
adoption rate of safety measures and recognition of landmarks. The criteria for
conversion to an open or subtotal cholecystectomy were at the discretion of each
surgeon. In contrast, perceptions of the impact of 30 intraoperative findings on
surgical difficulty (categorized by factors related to inflammation and
additional findings of the gallbladder and other intra-abdominal factors) were
consistent among surgeons. CONCLUSIONS: Intraoperative findings are objective and
considered to be appropriate indicators of surgical difficulty during LC.
PMID- 27490843
TI - Multimodal imaging for nonmelanoma skin cancer margin delineation.
AB - BACKGROUND AND OBJECTIVE: Nonmelanoma skin cancer (NMSC) is the most common form
of cancer worldwide. The most effective form of treating this cancer is its
surgical removal. As NMSC rarely metastasize, its complete excision is often
curative. We investigated the potential of combining Terahertz Pulsed Imaging
(TPI) with polarization enhanced reflectance optical imaging for the accurate
intraoperative delineation of NMSC. MATERIALS AND METHODS: Fresh thick samples
with residual cancer were obtained from surgeries. The samples were imaged within
two hours using polarization optical and TPI systems without remounting. Analysis
of the TPI results was performed in the frequency domain. Co- and cross-polarized
optical images were acquired at 410 nm. Superficial optical images were obtained
by subtracting cross-polarized from the respective co-polarized images.
Terahertz, optical, and histological images were overlaid and compared. RESULTS
AND CONCLUSIONS: Our results show that the frequency powers of diseased and
normal skin tissues differ significantly at 0.47 THz. While TPI has demonstrated
contrast between diseased and normal tissue, it can also highlight normal
structures. As TPI alone lacks the resolution necessary to distinguish between
tissue types morphologically, polarization optical imaging was used for the
inspection of the suspicious areas highlighted by TPI. Combined TPI and optical
imaging has the potential for quick intraoperative delineation of cancers. Lasers
Surg. Med. 49:319-326, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490844
TI - Correlation between "hourglass-like fascicular constriction" and idiopathic
anterior interosseous nerve palsy.
AB - INTRODUCTION: In recent operative cases of anterior interosseous nerve palsy
(AINP), hourglass-like fascicular constrictions have been reported. We
prospectively investigated the ultrasonographic history of these lesions to
better understand the role of this lesion in AINP. METHODS: Seven patients who
were diagnosed with idiopathic AINP based on classic clinical findings and had
hourglass-like fascicular constrictions found on ultrasonography were included.
All but 1 patient selected surgery, and we followed up all patients clinically
and with ultrasonography. RESULTS: In the 5 patients treated surgically in whom
paralysis recovered to a level greater than M4, postoperative ultrasonography
revealed less constriction. The other patient experienced little recovery after
surgery, and the severe constriction remained. In a conservatively treated
patient, the paralysis recovered completely, and upon ultrasonography, the
constriction had lessened. CONCLUSIONS: Although the mechanism is still unknown,
hourglass-like fascicular constriction lessened with relief of motor weakness
both in operatively and conservatively treated patients. Muscle Nerve 55: 508
512, 2017.
PMID- 27490846
TI - Cu,N-codoped Hierarchical Porous Carbons as Electrocatalysts for Oxygen Reduction
Reaction.
AB - It remains a huge challenge to develop nonprecious electrocatalysts with high
activity to substitute commercial Pt catalysts for oxygen reduction reactions
(ORR). Here, the Cu,N-codoped hierarchical porous carbon (Cu-N-C) with a high
content of pyridinic N was synthesized by carbonizing Cu-containing ZIF-8.
Results indicate that Cu-N-C shows excellent ORR electrocatalyst properties.
First of all, it nearly follows the four-electron route, and its electron
transfer number reaches 3.92 at -0.4 V. Second, both the onset potential and
limited current density of Cu-N-C are almost equal to those of a commercial Pt/C
catalyst. Third, it exhibits a better half-wave potential (~16 mV) than a
commercial Pt/C catalyst. More importantly, the Cu-N-C displays better stability
and methanol tolerance than the Pt/C catalyst. All of these good properties are
attributed to hierarchical structure, high pyridinic N content, and the synergism
of Cu and N dopants. The metal-N codoping strategy can significantly enhance the
activity of electrocatalysts, and it will provide reference for the design of
novel N-doped porous carbon ORR catalysts.
PMID- 27490845
TI - Race and mortality risk after radiation therapy in men treated with or without
androgen-suppression therapy for favorable-risk prostate cancer.
AB - BACKGROUND: African American (AA) men are more likely than non-AA men to have a
comorbid illness that could interact with androgen-deprivation therapy (ADT) and
shorten survival. This study assessed the impact that race had on the risk of all
cause mortality (ACM) and other-cause mortality (OCM) among men definitively
treated for favorable-risk prostate cancer (PC). METHODS: Between 1997 and 2013,
7252 men with low-risk or favorable intermediate-risk PC were treated with
brachytherapy with neoadjuvant ADT (n = 1501) or without neoadjuvant ADT (n =
5751) for a 4-month median duration. Cox and Fine-Gray multivariate regressions
were used to analyze whether the risk of ACM and OCM increased among AA men
versus non-AA men receiving ADT; adjustments were made for the age at
brachytherapy, year of brachytherapy, cardiometabolic comorbidity status, risk
group, and ADT treatment propensity score. RESULTS: After a median follow-up of
8.04 years, 869 men (12.0%) died: 48 (5.52%) of PC and 821 (94.48%) of other
causes. There was a significant association between AA race and an increased risk
of both ACM (adjusted hazard ratio [AHR], 1.77; 95% confidence interval [CI],
1.06-2.94; P = .028) and OCM (AHR, 1.86; 95% CI, 1.08-3.19; P = .024) among AA
men versus non-AA men who received ADT but not among those who did not receive
ADT (AHR for ACM, 1.33; 95% CI, 0.93-1.91; P = .12; AHR for OCM, 1.39; 95% CI,
0.96-2.02; P = .08). CONCLUSIONS: ADT use may shorten survival in AA men with
favorable-risk PC; therefore, its reservation for the treatment of higher risk
PC, for which level 1 evidence supports its use, should be considered. Cancer
2016;122:3608-14. (c) 2016 American Cancer Society.
PMID- 27490847
TI - Market Structure, Financial Dependence and Industrial Growth: Evidence from the
Banking Industry in Emerging Asian Economies.
AB - In this study, we examine the role of market structure for growth in financially
dependent industries from 10 emerging Asian economies over the period of 1995
2011. Our approach departs from existing studies in that we apply four
alternative measures of market structure based on structural and non-structural
approaches and compare their outcomes. Results indicate that higher bank
concentration may slow down the growth of financially dependent industries. Bank
competition on the other hand, allows financially dependent industries to grow
faster. These findings are consistent across a number of sensitivity checks such
as alternative measures of financial dependence, institutional factors (including
property rights, quality of accounting standards and bank ownership), and
endogeneity consideration. In sum, our study suggests that financially dependent
industries grow more in more competitive/less concentrated banking systems.
Therefore, regulatory authorities need to be careful while pursuing a
consolidation policy for banking sector in emerging Asian economies.
PMID- 27490848
TI - Effects of a Soluble Epoxide Hydrolase Inhibitor on Lipopolysaccharide-Induced
Acute Lung Injury in Mice.
AB - OBJECTIVES: Inflammation plays a key role in the pathogenesis of acute lung
injury (ALI). Soluble epoxide hydrolase (sEH) is suggested as a vital
pharmacologic target for inflammation. In this study, we determined whether a sEH
inhibitor, AUDA, exerts lung protection in lipopolysaccharide (LPS)-induced ALI
in mice. METHODS: Male BALB/c mice were randomized to receive AUDA or vehicle
intraperitoneal injection 4 h after LPS or phosphate buffered saline (PBS)
intratracheal instillation. Samples were harvested 24 h post LPS or PBS
administration. RESULTS: AUDA administration decreased the pulmonary levels of
monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha.
Improvement of oxygenation and lung edema were observed in AUDA treated group.
AUDA significantly inhibited sEH activity, and elevated epoxyeicosatrienoic acids
(EETs) levels in lung tissues. Moreover, LPS induced the activation of nuclear
factor (NF)-kappaB was markedly dampened in AUDA treated group. CONCLUSION:
Administration of AUDA after the onset of LPS-induced ALI increased pulmonary
levels of EETs, and ameliorated lung injury. sEH is a potential pharmacologic
target for ALI.
PMID- 27490849
TI - A Longitudinal Relationship Between Depressive Symptoms and Development of
Metabolic Syndrome: The Coronary Artery Risk Development in Young Adults Study.
AB - OBJECTIVE: Despite variability in the burden of elevated depressive symptoms by
sex and race and differences in the incidence of metabolic syndrome, few prior
studies describe the longitudinal association of depressive symptoms with
metabolic syndrome in a diverse cohort. We tested whether baseline and time
varying depressive symptoms were associated with metabolic syndrome incidence in
black and white men and women from the Coronary Artery Risk Development in Young
Adults study. METHODS: Participants reported depressive symptoms using the Center
for Epidemiologic Studies Depression Scale at four examinations between 1995 and
2010. At those same examinations, metabolic syndrome was determined. Cox
proportional hazards models were used to examine the associations of depressive
symptoms on the development of metabolic syndrome in 3208 participants without
metabolic syndrome at baseline. RESULTS: For 15 years, the incidence rate of
metabolic syndrome (per 10,000 person-years) varied by race and sex, with the
highest rate in black women (279.2), followed by white men (241.9), black men
(204.4), and white women (125.3). Depressive symptoms (per standard deviation
higher) were associated with incident metabolic syndrome in white men (hazard
ratio = 1.25, 95% confidence interval = 1.08-1.45) and white women (hazard ratio
= 1.17, 95% confidence interval = 1.00-1.37) after adjustment for demographic
characteristics and health behaviors. There was no significant association
between depression and metabolic syndrome among black men or black women.
CONCLUSIONS: Higher depressive symptoms contribute modestly to the onset of
metabolic syndrome among white adults.
PMID- 27490850
TI - Suggestions to Reduce Clinical Fibromyalgia Pain and Experimentally Induced Pain
Produce Parallel Effects on Perceived Pain but Divergent Functional MRI-Based
Brain Activity.
AB - OBJECTIVE: Hypnotic suggestion is an empirically validated form of pain control;
however, the underlying mechanism remains unclear. METHODS: Thirteen fibromyalgia
patients received suggestions to alter their clinical pain, and 15 healthy
controls received suggestions to alter experimental heat pain. Suggestions were
delivered before and after hypnotic induction with blood oxygen level-dependent
(BOLD) activity measured concurrently. RESULTS: Across groups, suggestion
produced substantial changes in pain report (main effect of suggestion, F2, 312 =
585.8; p < .0001), with marginally larger changes after induction (main effect of
induction, F1, 312 = 3.6; p = .060). In patients, BOLD response increased with
pain report in regions previously associated with pain, including thalamus and
anterior cingulate cortex. In controls, BOLD response decreased with pain report.
All changes were greater after induction. Region-of-interest analysis revealed
largely linear patient responses with increasing pain report. Control responses,
however, were higher after suggestion to increase or decrease pain from baseline.
CONCLUSIONS: Based on behavioral report alone, the mechanism of suggestion could
be interpreted as largely similar regardless of the induction or type of pain
experience. The functional magnetic resonance imaging data, however, demonstrated
larger changes in brain activity after induction and a radically different
pattern of brain activity for clinical pain compared with experimental pain.
These findings imply that induction has an important effect on underlying neural
activity mediating the effects of suggestion, and the mechanism of suggestion in
patients altering clinical pain differs from that in controls altering
experimental pain. Patient responses imply that suggestions altered pain
experience via corresponding changes in pain-related brain regions, whereas
control responses imply suggestion engaged cognitive control.
PMID- 27490851
TI - Association of Depressed Mood With Herpes Simplex Virus-2 Immunoglobulin-G Levels
in Pregnancy.
AB - OBJECTIVE: Depressed mood is common in pregnancy, is associated with stress, and
could result in immune suppression that may lead to latent herpes viral
reactivation. This study investigated whether depressed mood is associated with
higher herpes viral IgG levels in pregnant women. METHODS: Complete cross
sectional data from 247 pregnant women were available for this substudy. The data
included demographics, scores on the Perceived Stress Scale and Profile of Mood
States (POMS), and a panel of serum IgG levels for human herpesviruses. RESULTS:
Only the herpes simplex virus type 2 (HSV-2) (genital herpes) IgG level was
associated with Perceived Stress Scale and POMS-Depression/Dejection (POMS-D)
score. Hierarchical multiple regression analysis was used to examine the
association of POMS-D with herpesviral IgG levels adjusting for demographic
variables. In the final model, African American race (beta = .251, p < .001),
older age (beta = .199, p = .002), single marital status (beta = -.304, p <
.001), and depressed mood (beta = .122, p = .04) were associated with HSV-2 IgG
levels. In logistic regression, the strongest correlates of HSV IgG positivity
were single marital status, followed by POMS-D scores and African American race.
CONCLUSION: Genital herpes is a concern in pregnancy. Antibody titers may
indicate asymptomatic viral shedding, viral reactivation, or primary viral
infection. Antibody levels may be higher because of the immune changes during
pregnancy and potential immune effects of depressed mood causing reactivation of
latent HSV-2.
PMID- 27490852
TI - Risk for Incident Hypertension Associated With Posttraumatic Stress Disorder in
Military Veterans and the Effect of Posttraumatic Stress Disorder Treatment.
AB - OBJECTIVE: Posttraumatic stress disorder (PTSD) increases cardiovascular disease
and cardiovascular mortality risk. Neither the prospective relationship of PTSD
to incident hypertension risk nor the effect of PTSD treatment on hypertension
risk has been established. METHODS: Data from a nationally representative sample
of 194,319 veterans were drawn from the Veterans Administration (VA) roster of
United States service men and women. This included veterans whose end of last
deployment was from September 2001 to July 2010 and whose first VA medical visit
was from October 1, 2001 to January 1, 2009. Incident hypertension was modeled as
3 events: (1) a new diagnosis of hypertension and/or (2) a new prescription for
antihypertensive medication, and/or (3) a clinic blood pressure reading in the
hypertensive range (>=140/90 mm Hg, systolic/diastolic). Posttraumatic stress
disorder diagnosis was the main predictor. Posttraumatic stress disorder
treatment was defined as (1) at least 8 individual psychotherapy sessions of 50
minutes or longer during any consecutive 6 months and/or (2) a prescription for
selective serotonin reuptake inhibitor medication. RESULTS: Over a median 2.4
year follow-up, the incident hypertension risk independently associated with PTSD
ranged from hazard ratio (HR), 1.12 (95% confidence interval [CI], 1.08-1.17; p <
.0001) to HR, 1.30 (95% CI, 1.26-1.34; p < .0001). The interaction of PTSD and
treatment revealed that treatment reduced the PTSD-associated hypertension risk
(e.g., from HR, 1.44 [95% CI, 1.38-1.50; p < .0001] for those untreated, to HR,
1.20 [95% CI, 1.15-1.25; p < .0001] for those treated). CONCLUSIONS: These
results indicate that reducing the long-term health impact of PTSD and the
associated costs may require very early surveillance and treatment.
PMID- 27490854
TI - Lymphocyte enrichment using CD81-targeted immunoaffinity matrix.
AB - In mass cytometry, the isolation of pure lymphocytes is very important to obtain
reproducible results and to shorten the time spent on data acquisition. To
prepare highly purified cell suspensions of peripheral blood lymphocytes for
further analysis on mass cytometer, we used the new CD81+ immune affinity
chromatography cell isolation approach. Using 21 metal conjugated antibodies in a
single tube we were able to identify all basic cell subsets and compare their
relative abundance in final products obtained by density gradient (Ficoll-Paque)
and immune affinity chromatography (CD81+ T-catchTM) isolation approach. We show
that T-catch isolation approach results in purer final product than Ficoll-Paque
(P values 0.0156), with fewer platelets bound to target cells. As a result
acquisition time of 105 nucleated cells was 3.5 shorter. We then applied
unsupervised high dimensional analysis viSNE algorithm to compare the two
isolation protocols, which allowed us to evaluate the contribution of
unsupervised analysis over supervised manual gating. ViSNE algorithm effectively
characterized almost all supervised cell subsets. Moreover, viSNE uncovered
previously overseen cell subsets and showed inaccuracies in MaxparTM Human
peripheral blood phenotyping panel kit recommended gating strategy. These
findings emphasize the use of unsupervised analysis tools in parallel with
conventional gating strategy to mine the complete information from a set of
samples. They also stress the importance of the impurity removal to sensitively
detect rare cell populations in unsupervised analysis. (c) 2016 International
Society for Advancement of Cytometry.
PMID- 27490855
TI - Current Guidelines for the Diagnosis and Management of Hepatocellular Carcinoma:
A Comparative Review.
AB - OBJECTIVE: The purpose of this article is to review aspects of guidelines
pertinent to radiologists involved in the diagnosis or treatment of
hepatocellular carcinoma. CONCLUSION: Early diagnosis and treatment of
hepatocellular carcinoma are important because only 10% of patients meet the
criteria for curative therapy at the time of diagnosis. Several organizations
have developed guidelines for screening, diagnosis, and treatment of
hepatocellular carcinoma. Radiologists play a pivotal role in every aspect of
these guidelines.
PMID- 27490853
TI - Low-Grade Inflammation and Ambulatory Cortisol in Adolescents: Interaction
Between Interviewer-Rated Versus Self-Rated Acute Stress and Chronic Stress.
AB - OBJECTIVE: To determine whether the association between self-rated or interviewer
rated recent acute stress exposures and low-grade inflammation and daily cortisol
production in adolescents is moderated by chronic stress ratings. METHODS: Acute
and chronic stress exposures were assessed in 261 adolescents aged 13 to 16 years
using a semistructured life stress interview. The negative impact of acute
stressors was independently rated by both adolescents (self-rated) and
interviewers (interviewer-rated). Markers of inflammation (interleukin (IL)-6, IL
1ra, C-reactive protein) were measured from peripheral blood samples obtained via
antecubital venipuncture. Participants collected 4 saliva samples at home on each
of 6 consecutive days for the analysis of diurnal salivary cortisol profiles.
RESULTS: There were no main effects of acute stressors (self- and interviewer
rated) and chronic family or peer stress on adolescent inflammation markers and
cortisol (p values > .10). However, the interaction between interviewer-rated
acute stress and chronic family stress was significantly associated with
adolescent inflammation markers (IL-6, IL-1ra). Specifically, as chronic family
stress increased, the association between acute stressor impact (interviewer
rated) and inflammation markers became more positive (IL-6 (B = .054, SE = .023,
p = .022); IL-1ra (B = .030, SE = .014, p = .034)). Interactions between self
rated acute stress and chronic family stress were not associated with any
biological measures (p values > .10). Interactions between acute stressor impact
(both self- and interviewer-rated) and chronic peer stress were also not
significantly associated with any biological measures (p values > .05).
CONCLUSIONS: Among adolescents, interviewer-based ratings of acute stressor
impact may allow for better prediction of health-relevant inflammation markers
than adolescents' own ratings.
PMID- 27490856
TI - A Hidden Portrait by Edgar Degas.
AB - The preservation and understanding of cultural heritage depends increasingly on
in-depth chemical studies. Rapid technological advances are forging connections
between scientists and arts communities, enabling revolutionary new techniques
for non-invasive technical study of culturally significant, highly prized
artworks. We have applied a non-invasive, rapid, high definition X-ray
fluorescence (XRF) elemental mapping technique to a French Impressionist painting
using a synchrotron radiation source, and show how this technology can advance
scholarly art interpretation and preservation. We have obtained detailed
technical understanding of a painting which could not be resolved by conventional
techniques. Here we show 31.6 megapixel scanning XRF derived elemental maps and
report a novel image processing methodology utilising these maps to produce a
false colour representation of a "hidden" portrait by Edgar Degas. This work
provides a cohesive methodology for both imaging and understanding the chemical
composition of artworks, and enables scholarly understandings of cultural
heritage, many of which have eluded conventional technologies. We anticipate that
the outcome from this work will encourage the reassessment of some of the world's
great art treasures.
PMID- 27490857
TI - Systems Approaches and Big Data in Molecular Informatics.
PMID- 27490858
TI - PseDNA-Pro: DNA-Binding Protein Identification by Combining Chou's PseAAC and
Physicochemical Distance Transformation.
AB - Identification of DNA-binding proteins is an important problem in biomedical
research as DNA-binding proteins are crucial for various cellular processes.
Currently, the machine learning methods achieve the-state-of-the-art performance
with different features. A key step to improve the performance of these methods
is to find a suitable representation of proteins. In this study, we proposed a
feature vector composed of three kinds of sequence-based features, including
overall amino acid composition, pseudo amino acid composition (PseAAC) proposed
by Chou and physicochemical distance transformation. These features not only
consider the sequence composition of proteins, but also incorporate the sequence
order information of amino acids in proteins. The feature vectors were fed into
Support Vector Machine (SVM) for DNA-binding protein identification. The proposed
method is called PseDNA-Pro. Experiments on stringent benchmark datasets and
independent test datasets by using the Jackknife test showed that PseDNA-Pro can
achieve an accuracy of higher than 80 %, outperforming several state-of-the-art
methods, including DNAbinder, DNA-Prot, and iDNA-Prot. These results indicate
that the combination of various features for DNA-binding protein prediction is a
suitable approach, and the sequence-order information among residues in proteins
is relative for discrimination. For practical applications, a web-server of
PseDNA-Pro was established, which is available from
http://bioinformatics.hitsz.edu.cn/PseDNA-Pro/.
PMID- 27490859
TI - Illuminating Flash Point: Comprehensive Prediction Models.
AB - Flash point is an important property of chemical compounds that is widely used to
evaluate flammability hazard. However, there is often a significant gap between
the demand for experimental flash point data and their availability. Furthermore,
the determination of flash point is difficult and costly, particularly for some
toxic, explosive, or radioactive compounds. The development of a reliable and
widely applicable method to predict flash point is therefore essential. In this
paper, the construction of a quantitative structure - property relationship model
with excellent performance and domain of applicability is reported. It uses the
largest data set to date of 9399 chemically diverse compounds, with flash point
spanning from less than -130 degrees C to over 900 degrees C. The model employs
only computed parameters, eliminating the need for experimental data that some
earlier computational models required. The model allows accurate prediction of
flash point for a broad range of compounds that are unavailable or not yet
synthesized. This single model with a very broad range of chemical and flash
point applicability will allow accurate predictions of this important property to
be made for a broad range of new materials.
PMID- 27490861
TI - A Machine Learning Approach to Explain Drug Selectivity to Soluble and Membrane
Protein Targets.
AB - Improved understanding of the forces that determine drug specificity to their
targets is important for drug design and discovery, as well as for gaining
knowledge about molecular recognition. Here, we present a machine learning
approach that includes all approved drugs with a known protein target. The drugs
were characterized using easily interpretable physico-chemical descriptors.
Employing the Random Forest method, we were able to predict whether a drug binds
to a soluble or membrane protein with an average accuracy of 84 % and an average
area under curve of 0.91. The high average performance suggests that there exist
some general physico-chemical differences between drugs that bind to membrane and
soluble protein targets. Variable importance measures in combination with
permutation tests were used to find the most influential descriptors. This
resulted in six outstanding descriptors, that all involve drug flexibility and
lipophilicity, suggesting that drugs binding to membrane protein targets are in
general more flexible and lipophilic, and conversely, drugs binding to soluble
protein targets are more rigid and hydrophilic. With the notion that ligands in
general are blueprints of their protein pockets, we may also draw general
conclusions about the protein-pocket properties which may add to the
understanding of molecular recognition.
PMID- 27490860
TI - 3-Chlorotyramine Acting as Ligand of the D2 Dopamine Receptor. Molecular
Modeling, Synthesis and D2 Receptor Affinity.
AB - We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine
receptor. This compound displayed a similar affinity by this receptor to that
previously reported for dopamine. In order to understand further the experimental
results we performed a molecular modeling study of 3-chlorotyramine and
structurally related compounds. By combining molecular dynamics simulations with
semiempirical (PM6), ab initio and density functional theory calculations, a
simple and generally applicable procedure to evaluate the binding energies of
these ligands interacting with the D2 dopamine receptors is reported here. These
results provided a clear picture of the binding interactions of these compounds
from both structural and energetic view points. A reduced model for the binding
pocket was used. This approach allowed us to perform more accurate quantum
mechanical calculations as well as to obtain a detailed electronic analysis using
the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of
the binding interactions between ligands and the D2 dopamine receptor are
discussed in detail. A good correlation between the relative binding energies
obtained from theoretical calculations and experimental IC50 values was obtained.
These results allowed us to predict that 3-chlorotyramine possesses a significant
affinity by the D2 -DR. Our theoretical predictions were experimentally
corroborated when we synthesized and tested 3-chlorotyramine which displayed a
similar affinity by the D2 -DR to that reported for DA.
PMID- 27490862
TI - Predictive QSPR Modelling for the Second Virial Coefficient of the Pure Organic
Compounds.
AB - In this article we developed a system of the predictive models for the second
virial coefficients of the pure compounds. Second virial coefficient is the
property derived from the virial equation of state, and is of particular interest
as it describes pair intermolecular interactions. The two-layer QSPR models were
developed, which exploited the well-known physical equations and allowed us to
include this information into traditional QSPR methodology. This shows some new
perspectives for work with temperature-dependent properties. It was shown that 2D
descriptors can be successfully used for modeling of complex thermodynamic
properties like virial coefficients.
PMID- 27490863
TI - Multi-Server Approach for High-Throughput Molecular Descriptors Calculation based
on Multi-Linear Algebraic Maps.
AB - The present report introduces a novel module of the QuBiLS-MIDAS software for the
distributed computation of the 3D Multi-Linear algebraic molecular indices. The
main motivation for developing this module is to deal with the computational
complexity experienced during the calculation of the descriptors over large
datasets. To accomplish this task, a multi-server computing platform named T
arenal was developed, which is suited for institutions with many workstations
interconnected through a local network and without resources particularly
destined for computation tasks. This new system was deployed in 337 workstations
and it was perfectly integrated with the QuBiLS-MIDAS software. To illustrate the
usability of the T-arenal platform, performance tests over a dataset comprised of
15 000 compounds are carried out, yielding a 52 and 60 fold reduction in the
sequential processing time for the 2-Linear and 3-Linear indices, respectively.
Therefore, it can be stated that the T-arenal based distribution of computation
tasks constitutes a suitable strategy for performing high-throughput calculations
of 3D Multi-Linear descriptors over thousands of chemical structures for
posterior QSAR and/or ADME-Tox studies.
PMID- 27490864
TI - Sequential kidney-liver transplantation from the same living donor for lecithin
cholesterol acyl transferase deficiency.
AB - BACKGROUND: Lecithin cholesterol acyl transferase (LCAT) deficiency is a rare
autosomal recessive disorder of lipoprotein metabolism that results in end-stage
renal disease (ESRD) necessitating transplantation. As LCAT is produced in the
liver, combined kidney and liver transplantation was proposed to cure the
clinical syndrome of LCAT deficiency. METHODS: A 29-year-old male with ESRD
secondary to LCAT deficiency underwent a sequential kidney-liver transplantation
from the same living donor (LD). One year following the kidney transplant,
auxiliary partial orthotopic liver transplant (APOLT) of a left lateral segment
from the same donor was performed. RESULTS: At 5 years follow-up, there have been
no major complications, readmissions, or rejection episodes. Serum lipid
abnormalities recurred within the first year, but liver and kidney allograft
function remains intact. CONCLUSION: Few cases of sequential transplantation from
the same LD have been performed in adults. This is the first APOLT and multi
organ transplant performed for LCAT deficiency. Sequential organ transplant from
the same LD for ESRD secondary to a metabolic disorder of the liver is feasible
in adults and should be further investigated.
PMID- 27490865
TI - Failure of the IDA in FRET Systems at Close Inter-Dye Distances Is Moderated by
Frequent Low kappa(2) Values.
AB - Forster resonance energy transfer (FRET) is analyzed in terms of distance- and
orientation-dependent interactions between the transition dipole moments of the
involved donor and acceptor molecules. However, the ideal dipole approximation
(IDA) is known to fail at short donor-acceptor distances. In this work, we model
FRET in a Cy5- and Alexa Fluor 488-labeled double-stranded RNA by means of
combined molecular dynamics (MD) simulations and quantum-chemical calculations
involving the IDA as well as the more sophisticated monomer transition density
(MTD) approach. To this end, the relaxed ground-state geometries of the dyes were
fitted to the MD-based structures. Although substantial deviations between IDA
and MTD results can be observed for individual snapshots, the statistical impact
of the failure on the FRET rates is negligible in the chosen examples. Our
results clearly demonstrate that the IDA-based Forster model can still be applied
to systems with small donor-acceptor distances, provided that the dyes are not
trapped in arrangements with a high IDA failure and that the distribution of the
relative transition dipole orientations is fairly isotropic.
PMID- 27490867
TI - Dehydration of Methanediol in Aqueous Solution: An ONIOM(QM/MM) Study.
AB - We used ONIOM(QM/MM) method to examine the dehydration of a methanediol in
aqueous solution. A methanediol and a small number of water molecules in the
proximity of the methanediol are calculated with quantum mechanics (QM), while a
number of water molecules far from the methanediol are calculated with molecular
mechanics (MM). A molecular dynamical simulation shows that 12 water molecules
are located within the hydration shell of a methanediol. The energy barrier for
the dehydration of a methanediol decreases when we increase the number of water
molecules in the QM region and converges toward a finite value when 12 water
molecules are included in the QM region. This indicates a significant effect of
water molecules within the hydration shell on the dehydration process of a
methanediol in aqueous solution. The dehydration rate calculated with the
ONIOM(QM/MM) method agrees well with that obtained from a laboratory experiment.
PMID- 27490868
TI - Versatility of peptide nucleic acids (PNAs): role in chemical biology, drug
discovery, and origins of life.
AB - This review briefly discussed nomenclature, synthesis, chemistry, and biophysical
properties of a plethora of PNA derivatives reported since the discovery of
aegPNA. Different synthetic methods and structural analogs of PNA synthesized
till date were also discussed. An insight was gained into various chemical,
physical, and biological properties of PNA which make it preferable over all
other classes of modified nucleic acid analogs. Thereafter, various approaches
with special attention to the practical constraints, characteristics, and
inherent drawbacks leading to the delay in the development of PNA as gene
therapeutic drug were outlined. An explicit account of the successful application
of PNA in different areas of research such as antisense and antigene strategies,
diagnostics, molecular probes, and so forth was described along with the current
status of PNA as gene therapeutic drug. Further, the plausibility of the
existence of PNA and its role in primordial chemistry, that is, origin of life
was explored in an endeavor to comprehend the mystery and open up its deepest
secrets ever engaging and challenging the human intellect. We finally concluded
it with a discussion on the future prospects of PNA technology in the field of
therapeutics, diagnostics, and origin of life.
PMID- 27490869
TI - Negative-Pressure Wound Therapy in Acute Traumatic and Surgical Wounds in
Orthopaedics.
PMID- 27490870
TI - Treatment of Proximal Humeral Fractures: A Critical Analysis Review.
PMID- 27490871
TI - Treatment of Traumatic Segmental Long-Bone Defects: A Critical Analysis Review.
PMID- 27490873
TI - Tunnel Placement for the ACL During Reconstructive Surgery of the Knee: A
Critical Analysis Review.
PMID- 27490872
TI - Pathogenesis and Treatment of Dupuytren Disease.
PMID- 27490875
TI - From the Editor.
PMID- 27490874
TI - Advances in organ preservation for transplantation.
AB - Organ transplantation provides the best available therapy for a myriad of medical
conditions, including end-stage renal disease, hepatic failure and type I
diabetes mellitus. The current clinical reality is, however, that there is a
significant shortage of organs available for transplantation with respect to the
number of patients on organ waiting lists. As such, methods to increase organ
supply have been instituted, including improved donor management, organ
procurement and preservation strategies, living organ donation, transplantation
education and the increased utilization of donation after circulatory death and
expanded criteria donors. In particular, especially over the last decade, we have
witnessed a significant change in the way donor organs are preserved, away from
static cold storage methods to more dynamic techniques centred on machine
perfusion (MP). This review highlights the current state and future of organ
preservation for transplantation, focusing on both abdominal and thoracic organs.
In particular, we focus on MP preservation of renal, hepatic, pancreatic, cardiac
and lung allografts, also noting relevant advances in Australasia. MP of organs
after procurement holds considerable promise, and has the potential to
significantly improve graft viability and function post-transplantation,
especially in donors in whom acceptance criteria have been expanded.
PMID- 27490876
TI - Marginalization: A Revisitation With Integration of Scholarship on Globalization,
Intersectionality, Privilege, Microaggressions, and Implicit Biases.
AB - In 1994, the concept of marginalization was explored in an article in Advances in
Nursing Science. This is a revisitation of the concept incorporating new
scholarship. This update is founded on feminism, postcolonialism, critical race
theory, and discourse deconstruction, all viewpoints that have been explicated in
nursing. The purpose of this analysis is to look at new scholarship and concepts
useful to applying marginalization in nursing knowledge development from the
standpoint of Bourdieu's macro, meso, and micro levels. New scholarship includes
globalization, intersectionality, privilege, microaggressions, and implicit bias.
Implications for decreasing health disparities through this new scholarship are
discussed.
PMID- 27490877
TI - Social Justice as a Lens for Understanding Workplace Mistreatment.
AB - Workplace mistreatment can be viewed as a social injustice that prohibits one
from achieving optimal well-being. Cognitive and interpersonal skills required of
nurses can be impacted by workplace mistreatment, thus extending injustices by
violating the rights of patients to optimal care. The purpose of this article is
to view workplace mistreatment through the lens of Powers and Faden's theory of
social justice. Workplace mistreatment is explored through the 6 dimensions of
well-being, including health, personal security, reasoning, respect, attachment,
and self-determination, identified in the theory. The implications for practice
and policy are discussed and recommendations for research made.
PMID- 27490878
TI - Mixed-Methods Research in the Discipline of Nursing.
AB - In this review article, we examined the prevalence and characteristics of 294
mixed-methods studies in the discipline of nursing. Creswell and Plano Clark's
typology was most frequently used along with concurrent timing. Bivariate
statistics was most often the highest level of statistics reported in the
results. As for qualitative data analysis, content analysis was most frequently
used. The majority of nurse researchers did not specifically address the purpose,
paradigm, typology, priority, timing, interaction, or integration of their mixed
methods studies. Strategies are suggested for improving the design, conduct, and
reporting of mixed-methods studies in the discipline of nursing.
PMID- 27490879
TI - Using Theory Integration to Explore Complex Health Problems.
AB - Although nursing leaders call for theory utilization in research, use remains low
within the discipline. The purpose of this article is to explore the application
of interdisciplinary integration of models and theories to nursing research. An
example of theory integration for the purposes of guiding a study relevant to
school nursing is described. A conceptual-theoretical-empirical structure based
on the Neuman's systems model, a nursing theory, integrated with the social
communication model of pain, a psychology model, was developed to guide the study
to examine pain assessment for schoolchildren with intellectual and developmental
disabilities.
PMID- 27490880
TI - A Framework of Complex Adaptive Systems: Parents As Partners in the Neonatal
Intensive Care Unit.
AB - Advances in neonatal care are allowing for increased infant survival; however,
neurodevelopmental complications continue. Using a complex adaptive system
framework, a broad analysis of the network of agents most influential to
vulnerable infants in the neonatal intensive care unit (NICU) is presented:
parent, nurse, and organization. By exploring these interconnected relationships
and the emergent behaviors, a model of care that increases parental caregiving in
the NICU is proposed. Supportive parent caregiving early in an infant's NICU stay
has the potential for more sensitive caregiving and enhanced opportunities for
attachment, perhaps positively impacting neurodevelopment.
PMID- 27490881
TI - Nurses' Knowledge About Transgender Patient Care: A Qualitative Study.
AB - This study explored practicing nurses' knowledge of the needs of transgender
patients. Structured interviews were conducted with 268 nurses in the San
Francisco Bay Area. This study focused on the responses to 1 item in the 16-item
interview, "Describe health care issues that are particular to transgender
patients." Three themes emerged from the data: discomfort, transition, and harsh
consequences of being transgender. These findings revealed nurses' discomfort and
lack of knowledge about transgender people and their health care needs. Nursing
curricula must challenge the gender binary to better prepare nurses to provide
quality care for patients of all genders.
PMID- 27490882
TI - Teen Mothers' Experience of Intimate Partner Violence: A Metasynthesis.
AB - Pregnant and parenting teens suffer higher rates of intimate partner violence
(IPV) than older mothers. This qualitative metasynthesis explores teen mothers'
experience with IPV during pregnancy and postpartum. Organized by the metaphor of
a web, findings highlight how pervasive violence during childhood contributes to
teen pregnancy and the risk of IPV as violence is normalized. The web constricts
through the partner's control as violence emerges or worsens with pregnancy.
Young mothers become increasingly isolated, and live with the physical and
psychological consequences of IPV. Trauma-informed nursing practice is needed to
support teen mothers in violent intimate relationships to spin a new web.
PMID- 27490883
TI - Interpretation of Hospital Nurse Fatigue Using Latent Profile Analysis.
AB - There has been a lack of consensus in the literature related to the
conceptualization, definition, and measurement of hospital nurse fatigue. Using
latent profile analysis, the Hospital Nurse Force Theory provided a conceptual
format to identify 3 profiles of nurse fatigue from subjective reports of
hospital patient care nurses in a survey cohort. All fatigue and adaptation
variables demonstrated significant inverse relationships. Describing nurse
fatigue in profiles that include measures of acute, chronic, physical, and mental
fatigue dimensions provided a new and expanded view of nurse fatigue to monitor
trends comprehensively and evaluate fatigue risk management strategies.
PMID- 27490884
TI - Internet Recruitment of Asian American Breast Cancer Survivors.
AB - The purpose of this article is to identify practical issues in Internet
recruitment of racial/ethnic minorities by analyzing an Internet intervention
study conducted with Asian American breast cancer survivors, and to propose
directions for recruitment of racial/ethnic minorities for future Internet
research. Six practical issues were identified: (a) a relatively fewer number of
Internet communities/groups; (b) hindrances in establishing authenticity;
PMID- 27490886
TI - Understanding Influence within the Context of Nursing: Development of the Adams
Influence Model Using Practice, Research, and Theory.
AB - Acquiring influence, and knowing how to use it, is a required competency for
nurse leaders, yet the concept of influence and how it works is not well
described in the nursing literature. In this article, the authors examine what is
known about influence and present an influence model specific to nurse leaders.
The Adams Influence Model was developed through an iterative process and is based
on a comprehensive review of the influence literature, expert commentary,
multiple pilot studies, evaluation of nursing theories, and validation by an
external data source. Rather than defining "how to" influence, the model serves
as a guide for personal reflection, helping nurse leaders understand and reflect
on the influence process and factors, tactics, and strategies they can use when
seeking to influence others.
PMID- 27490885
TI - Clinical Growth: An Evolutionary Concept Analysis.
AB - Clinical growth is an essential component of nursing education, although
challenging to evaluate. Considering the paradigm shift toward constructivism and
student-centered learning, clinical growth requires an examination within
contemporary practices. A concept analysis of clinical growth in nursing
education produced defining attributes, antecedents, and consequences. Attributes
included higher-level thinking, socialization, skill development, self
reflection, self-investment, interpersonal communication, and linking theory to
practice. Identification of critical attributes allows educators to adapt to
student-centered learning in the clinical environment. These findings allow
educators to determine significant research questions, develop situation-specific
theories, and identify strategies to enhance student learning in the clinical
environment.
PMID- 27490887
TI - Atypical Fractures of the Femur: Evaluation and Treatment.
PMID- 27490888
TI - Association Between Intervertebral Disc Degeneration and Cigarette Smoking:
Clinical and Experimental Findings.
PMID- 27490889
TI - Use of Locking Plates in Orthopaedic Trauma Surgery.
PMID- 27490890
TI - Acute Fractures of the Tarsal Navicular: A Critical Analysis Review.
PMID- 27490891
TI - Spinopelvic Fixation in Complex Sacral Fractures.
PMID- 27490892
TI - The Metabolic Responses to L-Glutamine of Livers from Rats with Diabetes Types 1
and 2.
AB - There are several claims about the beneficial effects of supplementing L
glutamine to both type 1 and type 2 diabetes. The purpose of the present study
was to provide detailed knowledge about the fate of this amino acid in the liver,
the first organ that receives the compound when ingested orally. The study was
done using the isolated perfused rat liver, an experimental system that preserves
the microcirculation of the organ and that allows to measured several parameters
during steady-state and pre steady-state conditions. L-Glutamine was infused in
the portal vein (5 mM) and several parameters were monitored. Livers from type 1
diabetic rats showed an accelerated response to L-glutamine infusion. In
consequence of this accelerated response livers from type 1 diabetic rats
presented higher rates of ammonia, urea, glucose and lactate output during the
first 25-30 minutes following L-glutamine infusion. As steady-state conditions
approached, however, the difference between type 1 diabetes and control livers
tended to disappear. Measurement of the glycogen content over a period of 100
minutes revealed that, excepting the initial phase of the L-glutamine infusion,
the increased glucose output in livers from type 1 diabetic rats was mainly due
to accelerated glycogenolysis. Livers from type 2 diabetic rats behaved similarly
to control livers with no accelerated glucose output but with increased L-alanine
production. L-Alanine is important for the pancreatic beta-cells and from this
point of view the oral intake of L-glutamine can be regarded as beneficial.
Furthermore, the lack of increased glucose output in livers from type 2 diabetic
rats is consistent with observations that even daily L-glutamine doses of 30 g do
not increase the glycemic levels in well controlled type 2 diabetes patients.
PMID- 27490893
TI - Structural Implications on the Properties of Self-Assembling Supramolecular Hosts
for Fluorescent Guests.
AB - Nine amphiphilic macromolecules with decyl and oligo(ethylene glycol) side
chains, randomly distributed along a common poly(methacrylate) backbone, were
synthesized from the radical copolymerization of appropriate methacrylate
monomers. The resulting amphiphilic constructs differ in (1) the ratio between
their hydrophobic and hydrophilic components, (2) the length of their
oligo(ethylene glycol) chains, and/or (3) the molecular weight. When the ratio
between hydrophobic and hydrophilic segments is comprised between 6:1 and 1:2,
the macromolecules assemble spontaneously into particles with nanoscaled
dimensions in neutral buffer and capture hydrophobic borondipyrromethene
chromophores in their interior. However, the critical concentration required for
the assembly of these supramolecular hosts as well as their hydrodynamic
diameter, supramolecular weight, and number of constituent macromolecular
building blocks all vary monotonically with the ratio between hydrophobic and
hydrophilic components. Specifically, the critical concentration decreases and
the other three parameters increase as the relative hydrophobic content raises.
Furthermore, an increase in the relative hydrophobic content also discourages
interchromophoric interactions between entrapped guests in both ground and
excited states as well as delays access of potential quenchers. In fact, these
observations demonstrate that the hydrophobic components must be in excess over
their hydrophilic counterparts for optimal supramolecular hosts to assemble.
Indeed, a ratio of 6:1 between the numbers of decyl and oligo(ethylene glycol)
side chains appears to be ideal for this particular structural design. Under
these conditions, supramolecular hosts assemble spontaneously even at relatively
low polymer concentrations and their fluorescent guests do not escape into the
bulk aqueous solution, despite the reversibility of the noncovalent interactions
holding the supramolecular container together. Thus, these systematic
investigations provide invaluable structural guidelines to design self-assembling
supramolecular hosts with optimal composition for the effective encapsulation of
fluorescent guests and can lead to ideal delivery vehicles for the transport of
imaging probes to target locations in biological samples.
PMID- 27490894
TI - Taking advanced endovascular techniques out of the hospital: Ready for prime
time?
PMID- 27490895
TI - Redundancy and specificity in jasmonate signalling.
AB - Jasmonates (JAs) are essential phytohormones regulating plant development and
environmental adaptation. Many components of the JA-signalling pathway have been
identified. However, our insight into the mechanisms by which a single bioactive
JA hormone can regulate a myriad of physiological processes and provide
specificity in the response remains limited. Recent findings on molecular
components suggest that, despite apparent redundancy, specificity is achieved by
(1) distinct protein-protein interactions forming unique JAZ/transcription factor
complexes, (2) discrete spatiotemporal expression of specific components, (3)
variable hormone thresholds for the formation of multiple JA receptor complexes
and (4) integration of several signals by JA-pathway components. The molecular
modularity that is thereby created enables a single bioactive hormone to
specifically modulate multiple JA-outputs in response to different environmental
and developmental cues.
PMID- 27490896
TI - Renal Sympathetic Denervation in Rats Ameliorates Cardiac Dysfunction and
Fibrosis Post-Myocardial Infarction Involving MicroRNAs.
AB - BACKGROUND The role of renal sympathetic denervation (RSD) in ameliorating post
myocardial infarction (MI) left ventricular (LV) fibrosis via microRNA-dependent
regulation of connective tissue growth factor (CTGF) remains unknown. MATERIAL
AND METHODS MI and RSD were induced in Sprague-Dawley rats by ligating the left
coronary artery and denervating the bilateral renal nerves, respectively.
Norepinephrine, renin, angiotensin II and aldosterone in plasma, collagen,
microRNA21, microRNA 101a, microRNA 133a and CTGF in heart tissue, as well as
cardiac function were evaluated six weeks post-MI. RESULTS In the RSD group,
parameters of cardiac function were significantly improved as evidenced by
increased LV ejection fraction (p<0.01), LV end-systolic diameter (p<0.01), end
diastolic diameter (p<0.05), LV systolic pressure (p<0.05), maximal rate of
pressure rise and decline (dP/dtmax and dP/dtmin, p<0.05), and decreased LV end
diastolic pressure (p<0.05) when compared with MI rats. Further, reduced collagen
deposition in peri-infarct myocardium was observed in RSD-treated rats along with
higher microRNA101a and microRNA133a (p<0.05) and lower microRNA21 expression
(p<0.01) than in MI rats. CTGF mRNA and protein levels were decreased in LV
following RSD (p<0.01), accompanied by decreased expression of norepinephrine,
renin, angiotensin II and aldosterone in plasma (p<0.05) compared with untreated
MI rats. CONCLUSIONS The potential therapeutic effects of RSD on post-MI LV
fibrosis may be partly mediated by inhibition of CTGF expression via upregulation
of microRNA 101a and microRNA 133a and downregulation of microRNA21.
PMID- 27490897
TI - Elevated expression of human papillomavirus antigen in brain tissue of patients
with Rasmussen's encephalitis.
AB - OBJECTS: To investigate the expression of human papillomavirus (HPV)-specific
antigen in the brain tissue of patients with Rasmussen's Encephalitis (RE) and
its possible link to the clinical manifestation of RE. METHODS: The correlation
between RE and HPV antigen expression in brain tissue sections was investigated
using immunohistochemical (IHC) staining, pathological examination, MRI and
clinical manifestations. RESULTS: HPV antigen expression was elevated in three
out of four patients with RE, whereas there were no detectable HPV antigens in
six control patients. Significant staining for HPV antigen was located mainly
around or in the nucleus and cytoplasm of neurons. Among these RE patients, three
with elevated expression of HPV antigens had obvious hemisphere atrophy, whereas
the patient with negative staining for HPV antigens had mild atrophy.
CONCLUSIONS: Elevated expression of HPV antigens was observed in the brain tissue
of RE patients, which may correlate with hemisphere atrophy. Thus, our results
may suggest that HPV infection or being a carrier of HPV may play a role in the
initiation and progression of RE.
PMID- 27490898
TI - Glycyrrhizin ameliorates oxidative stress and inflammation in hippocampus and
olfactory bulb in lithium/pilocarpine-induced status epilepticus in rats.
AB - Glycyrrhizin (GL) is a triterpene present in the roots and rhizomes of
Glycyrrhiza glabra that has anti-inflammatory, hepatoprotective and
neuroprotective effects. Recently, it was demonstrated that GL produced
neuroprotective effects on the postischemic brain as well as on the kainic acid
injury model in rats. In addition to this, GL also prevented excitotoxic effects
on primary cultures. The aims of the present study were to evaluate GL scavenging
properties and to investigate GL's effect on oxidative stress and inflammation in
the lithium/pilocarpine-induced seizure model in two cerebral regions,
hippocampus and olfactory bulb, at acute time intervals (3 or 24h) after status
epilepticus (SE). Fluorometric methods showed that GL scavenged three reactive
oxygen species: hydrogen peroxide, peroxyl radicals and superoxide anions. In
contrast, GL was unable to scavenge peroxynitrite, hydroxyl radicals, singlet
oxygen and 2,2-diphenil-1-picrylhydrazyl (DPPH) radicals suggesting that GL is a
weak scavenger. Additionally, administration of GL (50mg/kg, i.p.) 30min before
pilocarpine administration significantly suppressed oxidative stress. Moreover,
malondialdehyde levels were diminished and glutathione levels were maintained at
control values in both cerebral regions at 3 and 24 after SE. At 24h after SE,
glutathione S-transferase and superoxide dismutase activity increased in the
hippocampus, while both glutathione reductase and glutathione peroxidase activity
were unchanged in the olfactory bulb at that time. In addition, GL suppressed the
induction of the proinflammatory cytokines interleukin-1 beta (IL-1beta) and
tumor necrosis factor alpha (TNF-alpha) in both cerebral regions evaluated. These
results suggest that GL confers protection against pilocarpine damage via
antioxidant and anti-inflammatory effects.
PMID- 27490899
TI - Sex determination by three-dimensional geometric morphometrics of craniofacial
form.
AB - SUMMARY: The purpose of the present study is to define which regions of the
cranium, the upper-face, the orbits and the nasal are the most sexually
dimorphic, by using three-dimensional geometric morphometric methods, and
investigate the effectiveness of this method in determining sex from the shape of
these regions. The study sample consisted of 176 crania of known sex (94 males,
82 females) belonging to individuals who lived in Greece during the 20(th)
century. The three-dimensional co-ordinates of 31 ecto-cranial landmarks were
digitized using a MicroScribe 3DX contact digitizer. Goodall's F-test was
performed in order to compare statistical differences in shape between males and
females. Generalized Procrustes Analysis (GPA) was used to obtain size and shape
variables for statistical analysis. Shape, Size and Form analyses were carried
out by logistic regression and discriminant function analysis. The results
indicate that there are shape differences between the sexes in the upper-face and
the orbits. The highest shape classification rate was obtained from the upper
face region. The centroid size of the caraniofacial and the orbital regions was
smaller in females than males. Moreover, it was found that size is significant
for sexual dimorphism in the upper-face region. As anticipated, the
classification accuracy improves when both size and shape are combined. The
findings presented here constitute a firm basis upon which further research can
be conducted.
PMID- 27490901
TI - A Scheduling Algorithm for Cloud Computing System Based on the Driver of Dynamic
Essential Path.
AB - To solve the problem of task scheduling in the cloud computing system, this paper
proposes a scheduling algorithm for cloud computing based on the driver of
dynamic essential path (DDEP). This algorithm applies a predecessor-task layer
priority strategy to solve the problem of constraint relations among task nodes.
The strategy assigns different priority values to every task node based on the
scheduling order of task node as affected by the constraint relations among task
nodes, and the task node list is generated by the different priority value. To
address the scheduling order problem in which task nodes have the same priority
value, the dynamic essential long path strategy is proposed. This strategy
computes the dynamic essential path of the pre-scheduling task nodes based on the
actual computation cost and communication cost of task node in the scheduling
process. The task node that has the longest dynamic essential path is scheduled
first as the completion time of task graph is indirectly influenced by the
finishing time of task nodes in the longest dynamic essential path. Finally, we
demonstrate the proposed algorithm via simulation experiments using Matlab tools.
The experimental results indicate that the proposed algorithm can effectively
reduce the task Makespan in most cases and meet a high quality performance
objective.
PMID- 27490900
TI - Limited Genetic Connectivity between Gorgonian Morphotypes along a Depth
Gradient.
AB - Gorgonian species show a high morphological variability in relation to the
environment in which they live. In coastal areas, parameters such as temperature,
light, currents, and food availability vary significantly with depth, potentially
affecting morphology of the colonies and the structure of the populations, as
well as their connectivity patterns. In tropical seas, the existence of
connectivity between shallow and deep populations supported the hypothesis that
the deep coral reefs could potentially act as (reproductive) refugia fostering re
colonization of shallow areas after mortality events. Moreover, this hypothesis
is not so clear accepted in temperate seas. Eunicella singularis is one of the
most common gorgonian species in Northwestern Mediterranean Sea, playing an
important role as ecosystem engineer by providing biomass and complexity to the
coralligenous habitats. It has a wide bathymetric distribution ranging from about
10 m to 100 m. Two depth-related morphotypes have been identified, differing in
colony morphology, sclerite size and shape, and occurrence of symbiotic algae,
but not in mitochondrial DNA haplotypes. In the present study the genetic
structure of E. singularis populations along a horizontal and bathymetric
gradient was assessed using microsatellites and ITS1 sequences. Restricted gene
flow was found at 30-40 m depth between the two Eunicella morphotypes.
Conversely, no genetic structuring has been found among shallow water populations
within a spatial scale of ten kilometers. The break in gene flow between shallow
and deep populations contributes to explain the morphological variability
observed at different depths. Moreover, the limited vertical connectivity hinted
that the refugia hypothesis does not apply to E. singularis. Re-colonization of
shallow water populations, occasionally affected by mass mortality events, should
then be mainly fueled by larvae from other shallow water populations.
PMID- 27490903
TI - Radiotherapy Deferral in Medulloblastoma.
PMID- 27490904
TI - Prone sleeping and SUDEP risk: The dynamics of body positions in nonfatal
convulsive seizures.
AB - BACKGROUND: Most victims of sudden unexpected death in epilepsy (SUDEP) are found
prone with signs suggestive of an unwitnessed convulsive seizure (CS). Prone
sleeping has been proposed as a risk factor for SUDEP. Little is known, however,
about the change of body position during the course of CSs. METHODS: We
retrospectively reviewed video-EEG data and assessed body positions during the
course of CSs, until there was a physical interaction by nursing staff with the
subject. RESULTS: We identified 180 CSs in 90 individuals. In 16 of the 180 CSs
(9%), the subject started in or turned to the prone position. Of the seven CSs
that started in the prone position, three turned to a lateral position during the
CS. In 13 CSs, the subject was in prone position at time of nursing intervention;
nine (69%) of these started in a nonprone position. DISCUSSION: Our data suggest
that the prone position occurs infrequently in closely supervised nonfatal CSs, a
notable contrast to the number of victims of SUDEP found prone. Whether prone
sleeping prior to CSs increases SUDEP risk, however, remains speculative, as body
position during the course of a CS appeared to be dynamic.
PMID- 27490902
TI - Interaction with PALB2 Is Essential for Maintenance of Genomic Integrity by
BRCA2.
AB - Human breast cancer susceptibility gene, BRCA2, encodes a 3418-amino acid protein
that is essential for maintaining genomic integrity. Among the proteins that
physically interact with BRCA2, Partner and Localizer of BRCA2 (PALB2), which
binds to the N-terminal region of BRCA2, is vital for its function by
facilitating its subnuclear localization. A functional redundancy has been
reported between this N-terminal PALB2-binding domain and the C-terminal DNA
binding domain of BRCA2, which undermines the relevance of the interaction
between these two proteins. Here, we describe a genetic approach to examine the
functional significance of the interaction between BRCA2 and PALB2 by generating
a knock-in mouse model of Brca2 carrying a single amino acid change (Gly25Arg,
Brca2G25R) that disrupts this interaction. In addition, we have combined
Brca2G25R homozygosity as well as hemizygosity with Palb2 and Trp53
heterozygosity to generate an array of genotypically and phenotypically distinct
mouse models. Our findings reveal defects in body size, fertility, meiotic
progression, and genome stability, as well as increased tumor susceptibility in
these mice. The severity of the phenotype increased with a decrease in the
interaction between BRCA2 and PALB2, highlighting the significance of this
interaction. In addition, our findings also demonstrate that hypomorphic
mutations such as Brca2G25R have the potential to be more detrimental than the
functionally null alleles by increasing genomic instability to a level that
induces tumorigenesis, rather than apoptosis.
PMID- 27490905
TI - Diagnostic accuracy of audio-based seizure detection in patients with severe
epilepsy and an intellectual disability.
AB - We evaluated the performance of audio-based detection of major seizures (tonic
clonic and long generalized tonic) in adult patients with intellectual disability
living in an institute for residential care. METHODS: First, we checked in a
random sample (n=17, 102 major seizures) how many patients have recognizable
sounds during these seizures. In the second part of this trial, we followed 10
patients (who had major seizures with recognizable sounds) during four weeks with
an acoustic monitoring system developed by CLB ('CLB-monitor') and video camera.
In week 1, we adapted the sound detection threshold until, per night, a maximum
of 20 sounds was found. During weeks 2-4, we selected the epilepsy-related sounds
and performed independent video verification and labeling ('snoring', 'laryngeal
contraction') of the seizures. The video images were also fully screened for
false negatives. In the third part, algorithms in the CLB-monitor detected one
specific sound (sleep-related snoring) to illustrate the value of automatic sound
recognition. RESULTS: Part 1: recognizable sounds (louder than whispering)
occurred in 23 (51%) of the 45 major seizures, 20 seizures (45%) were below this
threshold, and 2 (4%) were without any sound. Part 2: in the follow-up group
(n=10, 112 major seizures; mean: 11.2, range: 1-30), we found a mean sensitivity
of 0.81 (range: 0.33-1.00) and a mean positive predictive value of 0.40 (range:
0.06-1.00). All false positive alarms (mean value: 1.29 per night) were due to
minor seizures. We missed 4 seizures (3%) because of lack of sound and 10 (9%)
because of sounds below the system threshold. Part 3: the machine-learning
algorithms in the CLB-monitor resulted in an overall accuracy for 'snoring' of
98.3%. CONCLUSIONS: Audio detection of major seizures is possible in half of the
patients. Lower sound detection thresholds may increase the proportion of
suitable candidates. Human selection of seizure-related sounds has a high
sensitivity and moderate positive predictive value because of minor seizures
which do not need intervention. Algorithms in the CLB-monitor detect seizure
related sounds and may be used alone or in multimodal systems.
PMID- 27490906
TI - Ezio Sciamanna: The Italian contribution to the origin of cortical stimulation
mapping in humans.
AB - Influenced by Ferrier's 1873 publication documenting his initial experience with
cortical stimulation mapping (CSM) across several species, 19th-century
experiments applying electric current to exposed human brain soon followed.
Bartholow is commonly credited with the first report of CSM in a conscious human
in 1874. What is not well established is that prominent Italian neurologist, Ezio
Sciamanna, localized sensorimotor function in a human demonstration of CSM
shortly thereafter in 1882. Sciamanna was in the vanguard of functional
localization of brain function through direct stimulation of human gray matter.
Unlike Bartholow, who has been canonized in the annals of CSM, Sciamanna has
remained relatively obscure, despite the fact that his case may represent a
better example of true subdural CSM than his better known contemporary.
PMID- 27490907
TI - Use of thrombin-based haemostatic matrix in head and neck reconstructions: a
potential risk factor for pulmonary embolism.
AB - BACKGROUND: Haemostatic agents including thrombin-based haemostatic matrix are
widely used in patients undergoing cardiac, vascular and spinal surgery. These
agents promote local haemostasis through activation of the clotting cascade. To
our knowledge, this case series is the first report of pulmonary embolization
associated with FloSeal following head and neck oncology resection and free flap
reconstruction. METHODS: We present five patients who were diagnosed with
symptomatic pulmonary embolism after oncologic head and neck free flap
reconstructions in 2014 and 2015. RESULTS: There were five patients consisting of
three males and two females. The mean age was 67 years, ranging from 60 to 74
years. Pulmonary embolism occurred between 3 and 30 days with a mean of 12 days.
Four out of the five reported cases showed involvement of more than one lobe, and
two cases had bilateral pulmonary involvement. All but one patient underwent
infratemporal fossa dissections as part of the cancer resection. Ten millilitres
of FloSeal was applied to the pterygoid plexi in the four patients to achieve
haemostasis. All patients received heparin infusion followed by warfarin therapy
for at least 6 months with no mortality or complications relating to pulmonary
embolism to date. CONCLUSION: Although inconclusive due to study design and small
numbers, this series raises the possibility that there may be an association
between the use of haemostatic matrix in head and neck oncologic reconstructions
and pulmonary embolism. Haemostatic matrix must be used in caution when there is
a direct contact with venous endolumens such as the pterygoid plexus and soleus.
PMID- 27490909
TI - Multimorbidity in people with chronic kidney disease: implications for outcomes
and treatment.
AB - PURPOSE OF REVIEW: With ageing populations, the prevalence of multimorbidity is
increasing. This review discusses recent developments in the understanding of
multimorbidity in the context of chronic kidney disease (CKD). It explores the
associated treatment burden and the implications for key outcomes and patient
care. RECENT FINDINGS: Comorbidity and polypharmacy are common in CKD, even at
early stages, and are associated with significant treatment burden. Both
'concordant' and 'discordant' comorbidities have a negative impact on mortality,
cardiovascular disease, hospitalisation and length of stay. In addition, quality
of life is influenced by many factors beyond CKD, including comorbidities and
certain medications. Several factors may reduce treatment burden for people with
CKD, though research on this is at an early stage. Although patient activation is
desirable to support self-management amongst people with multimorbidity, there
are significant challenges that impact patient capacity amongst elderly
populations with complex needs. SUMMARY: Comorbidities are common in CKD and have
important implications for patients, clinicians and health services.
PMID- 27490908
TI - Epidemiologic Trends of Chemical Ocular Burns in the United States.
AB - Importance: Determining the national epidemiologic trends of chemical ocular
burns can assist physicians and policy makers in appropriate allocation of
resources for treatment and prevention. Objective: To describe the epidemiologic
trends and risk factors for chemical burns of the eye. Design, Setting, and
Participants: Between August 1, 2015, and April 25, 2016, data from the
Nationwide Emergency Department Sample were analyzed from January 1, 2010,
through December 31, 2013. A sample of 900 emergency departments (EDs) across the
United States was used. Patients presenting to EDs with a diagnosis of alkali or
acid ocular burn, chemical conjunctivitis, or a combination of nonspecific ocular
chemical burn and chemical poisoning or toxic effects were eligible for
inclusion. Injured patients' age, sex, primary health care insurance, income
quartile, and other demographics were described. A subset consisting of those
injuries identified as alkaline or acidic burns was further characterized. Main
Outcomes and Measures: Age-specific rates of ED presentation for chemical ocular
burn injuries, independent factors associated with all, alkali, and acid
injuries, and total ED-associated charges. Results: From January 1, 2010, through
December 31, 2013, a total of 144 149 chemical ocular burns were diagnosed at EDs
nationwide. Men represented 56.6% of all cases (n = 81 496). Median age was 32
years, with female patients presenting at a younger age than male patients
(median of 32 vs 34 years; P < .001). Injury rates were highest among children
aged 1 to 2 years (28.61 and 23.49 injuries per 100 000 population,
respectively). Adults aged between 18 and 64 years also have these injuries at an
increased rate, although this rate was half that of infants (mean, 13.28 per 100
000 population). Alkali injuries were more common than acid injuries (53.6% [n =
9137; 95% CI, 51.6%-56.0%] vs 46.4% [n = 7909; 95% CI, 44.0%-48.9%]), and all
chemical eye injuries most commonly occur in residential locations (10.3% [n = 14
772]; 95% CI, 9.6%-10.9%) and among individuals in the first and second (lowest
and second-lowest) income quartiles (<=$48 749) (56.0% [n = 80 691]; 95% CI,
54.4%-57.7%). Injuries most commonly occurred among those who had private health
care insurance (31.9% [n = 45 900]; 95% CI, 30.9%-32.9%), and occurred more in
the South (36.8% [n = 53 008]; 95% CI, 34.6%-39.1%). Emergency department charges
due to these injuries totaled $106.7 million. Conclusions and Relevance: Young
children represent the single highest-risk group for ocular chemical injuries.
Education and other interventions concerned with preventing these injuries will
be most effective if used accordingly.
PMID- 27490910
TI - Gunshot Injuries to the Spine.
PMID- 27490911
TI - Femoral Head Fractures.
PMID- 27490912
TI - A Review of Current Graft Options for Anterior Cruciate Ligament Reconstruction.
PMID- 27490913
TI - Avoiding Complications in Periacetabular Osteotomy.
PMID- 27490914
TI - Structure of Chiral Au44(2,4-DMBT)26 Nanocluster with an 18-Electron Shell
Closure.
AB - The 18-electron shell closure structure of Au nanoclusters protected by thiol
ligands has not been reported until now. Herein, we synthesize a novel
nanocluster bearing the same gold atom number but a different thiolate number as
another structurally resolved nanocluster Au44(TBBT)28 (TBBTH = 4-tert
butylbenzenelthiol). The new cluster was determined to be Au44(2,4-DMBT)26 (2,4
DMBTH = 2,4-dimethylbenzenethiol) using multiple techniques, including mass
spectrometry and single crystal X-ray crystallography (SCXC). Au44(2,4-DMBT)26
represents the first 18-electron closed-shell gold nanocluster. SCXC reveals that
the atomic structure of Au44(2,4-DMBT)26 is completely different from that of
Au44(TBBT)28 but is similar to the structure of Au38Q. The arrangement of staples
(bridging thiolates) and part of the Au29 kernel atom induces the chirality of
Au44(2,4-DMBT)26. The finding that a small portion of the gold kernel exhibits
chirality is interesting because it has not been previously reported to the best
of our knowledge. Although Au44(2,4-DMBT)26 bears an 18-electron shell closure
structure, it is less thermostable than Au44(TBBT)28, indicating that multiple
factors contribute to the thermostability of gold nanoclusters. Surprisingly, the
small difference in Au/thiolate molar ratio between Au44(2,4-DMBT)26 and
Au44(TBBT)28 leads to a dramatic distinction in Au 4f X-ray photoelectron
spectroscopy, where it is found that the charge state of Au in Au44(2,4-DMBT)26
is remarkably more positive than that in Au44(TBBT)28 and even slightly more
positive than the charge states of gold in Au-(2,4-DMBT) or Au-TBBT complexes.
PMID- 27490915
TI - Dapagliflozin as Additional Treatment to Liraglutide and Insulin in Patients With
Type 1 Diabetes.
AB - CONTEXT: It is imperative that novel approaches to treatment of type 1 diabetes
(T1D) are devised. OBJECTIVE: The objective of the study was to investigate
whether addition of dapagliflozin to insulin and liraglutide results in a
significant reduction in glycemia and body weight. DESIGN: This was a randomized
clinical trial. SETTING: The study was conducted at a single academic medical
center. PARTICIPANTS: Participants included T1D patients on liraglutide therapy
for at least last 6 months. INTERVENTION: Thirty T1D patients were randomized (in
2:1 ratio) to receive either dapagliflozin 10 mg or placebo daily for 12 weeks.
MAIN OUTCOME MEASURE: Change in mean glycated hemoglobin after 12 weeks of
dapagliflozin when compared with placebo was measured. RESULTS: In the
dapagliflozin group, glycated hemoglobin fell by 0.66% +/- 0.08% from 7.8% +/-
0.21% (P < .01 vs placebo), whereas it did not change significantly in the
placebo group from 7.40% +/- 0.20% to 7.30% +/- 0.20%. The body weight fell by1.9
+/- 0.54kg (P < .05 vs placebo). There was no additional hypoglycemia (blood
glucose < 3.88 mmol/L; P = .52 vs placebo). In the dapagliflozin group, there
were significant increases in the plasma concentrations of glucagon by 35% +/-
13% (P < .05), hormone-sensitive lipase by 29% +/- 11% (P < .05), free fatty
acids by 74% +/- 32% (P < .05), acetoacetate by 67% +/- 34% (P < .05), and beta
hydroxybutyrate by 254% +/- 81% (P < .05). Urinary ketone levels also increased
significantly (P < .05). None of these changes was observed in the placebo group.
Two patients in the dapagliflozin group developed diabetic ketoacidosis.
CONCLUSIONS: Addition of dapagliflozin to insulin and liraglutide in patients
with T1D results in a significant improvement in glycemia and weight loss while
increasing ketosis. If it is decided to use this approach, then it must be used
only by a knowledgeable patient along with an endocrinologist who is well versed
with it.
PMID- 27490916
TI - Use of Estrogen-Containing Contraception Is Associated With Increased
Concentrations of 25-Hydroxy Vitamin D.
AB - CONTEXT: Small studies suggest exogenous estrogen may improve vitamin D status,
but the etiology is unclear because women who use hormones may make lifestyle
choices that differentially affect vitamin D status. OBJECTIVE: Our objective was
to investigate the association between use of hormonal contraception and 25
hydroxy-vitamin D (25(OH)D). DESIGN: We used linear regression modeling of cross
sectional data to estimate percent change in season-adjusted serum 25(OH)D with
estrogen use after adjustment for other factors. SETTING: At the enrollment
clinic visit (2010-2012) into a cohort study of uterine fibroids, each subject
provided a blood sample, had anthropomorphic variables and skin reflectance
measured, and answered questionnaires on demographics, dietary and supplement
intake, contraceptive use, reproductive and medical history, and behaviors.
PARTICIPANTS: A total of 1662 African American women, community volunteers, 23-34
years old, living in the Detroit, Michigan, area were included. INTERVENTIONS:
None. MAIN OUTCOMES AND MEASURES: Serum 25(OH)D was measured. RESULTS: Serum
25(OH)D concentrations were low (70% <20 ng/ml). Current use of an estrogen
containing contraceptive was associated with a 20% (95% confidence interval: 14
27) increase in 25(OH)D after adjustment. There was no increase in 25(OH)D among
participants who had used estrogen in the past, but were not current users,
indicating that results were unlikely to be due to unmeasured confounding by
factors related to contraceptive choice. CONCLUSIONS: The increase in 25(OH)D
with use of estrogen-containing contraceptives raise mechanistic questions
regarding the biological pathways involved, and highlights the need for studies
that examine possible endogenous estrogen effects on vitamin D.
PMID- 27490917
TI - A Probabilistic Model for Cushing's Syndrome Screening in At-Risk Populations: A
Prospective Multicenter Study.
AB - CONTEXT: Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence
of CS in specific patient populations has been reported, but routine screening
for CS remains questionable. To decrease the diagnostic delay and improve disease
outcomes, simple new screening methods for CS in at-risk populations are needed.
OBJECTIVE: To develop and validate a simple scoring system to predict CS based on
clinical signs and an easy-to-use biochemical test. DESIGN: Observational,
prospective, multicenter. SETTING: Referral hospital. PATIENTS: A cohort of 353
patients attending endocrinology units for outpatient visits. INTERVENTIONS: All
patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose
dexamethasone suppression test for CS. MAIN OUTCOME MEASURES: Diagnosis or
exclusion of CS. RESULTS: Twenty-six cases of CS were diagnosed in the cohort. A
risk scoring system was developed by logistic regression analysis, and cutoff
values were derived from a receiver operating characteristic curve. This risk
score included clinical signs and symptoms (muscular atrophy, osteoporosis, and
dorsocervical fat pad) and LNSC levels. The estimated area under the receiver
operating characteristic curve was 0.93, with a sensitivity of 96.2% and
specificity of 82.9%. CONCLUSIONS: We developed a risk score to predict CS in an
at-risk population. This score may help to identify at-risk patients in non
endocrinological settings such as primary care, but external validation is
warranted.
PMID- 27490918
TI - The Effects of Soy Isoflavones on Metabolic Status of Patients With Polycystic
Ovary Syndrome.
AB - CONTEXT: Limited data are available evaluating the effects of soy isoflavones on
metabolic status of patients with polycystic ovary syndrome (PCOS). OBJECTIVE:
The current study was performed to determine the effects of soy isoflavones on
metabolic status of patients with PCOS. METHODS: This randomized, double-blind,
placebo-controlled trial was performed on 70 women diagnosed with PCOS according
to the Rotterdam criteria who were 18-40 years old. Participants were randomly
allocated into two groups to take either 50 mg/d soy isoflavones (n = 35) or
placebo (n = 35) for 12 weeks. Metabolic, endocrine, inflammation, and oxidative
stress biomarkers were quantified at the beginning of the study and after the 12
week intervention. RESULTS: After 12 weeks of intervention, compared to the
placebo group, soy isoflavone administration significantly decreased circulating
serum levels of insulin (-1.2 +/- 4.0 vs +2.8 +/- 4.7 MUIU/mL; P < .001) and
homeostasis model of assessment-estimated insulin resistance (-0.3 +/- 1.0 vs
+0.6 +/- 1.1; P < .001) and increased the quantitative insulin sensitivity check
index (+0.0009 +/- 0.01 vs -0.01 +/- 0.03; P = .01). Supplementation with soy
isoflavones resulted in significant reductions in free androgen index (-0.03 +/-
0.04 vs +0.02 +/- 0.03; P < .001) and serum triglycerides (-13.3 +/- 62.2 vs
+10.3 +/- 24.5 mg/dL; P = .04) compared to the placebo group. There was a
significant increase in plasma total glutathione (+96.0 +/- 102.2 vs +22.7 +/-
157.8 MUmol/L; P = .04) and a significant decrease in malondialdehyde levels (
0.7 +/- 0.8 vs +0.8 +/- 2.3 MUmol/L; P = .001) by soy isoflavone intake compared
with the placebo group. We did not observe any significant effect of soy
isoflavone intake on other lipid profiles and inflammatory and oxidative stress
markers. CONCLUSION: Soy isoflavone administration for 12 weeks in women with
PCOS significantly improved markers of insulin resistance, hormonal status,
triglycerides, and biomarkers of oxidative stress.
PMID- 27490919
TI - Energy Metabolic Adaptation and Cardiometabolic Improvements One Year After
Gastric Bypass, Sleeve Gastrectomy, and Gastric Band.
AB - CONTEXT: It is not known whether the magnitude of metabolic adaptation, a greater
than expected drop in energy expenditure, depends on the type of bariatric
surgery and is associated with cardiometabolic improvements. OBJECTIVE: To
compare changes in energy expenditure (metabolic chamber) and circulating
cardiometabolic markers 8 weeks and 1 year after Roux-en-y bypass (RYGB), sleeve
gastrectomy (SG), laparoscopic adjustable gastric band (LAGB), or a low-calorie
diet (LCD). Design, Setting, Participants, and Intervention: This was a parallel
arm, prospective observational study of 30 individuals (27 females; mean age, 46
+/- 2 years; body mass index, 47.2 +/- 1.5 kg/m2) either self-selecting bariatric
surgery (five RYGB, nine SG, seven LAGB) or on a LCD (n = 9) intervention (800
kcal/d for 8 weeks, followed by weight maintenance). RESULTS: After 1 year, the
RYGB and SG groups had similar degrees of body weight loss (33-36%), whereas the
LAGB and LCD groups had 16 and 4% weight loss, respectively. After adjusting for
changes in body composition, 24-hour energy expenditure was significantly
decreased in all treatment groups at 8 weeks (-254 to -82 kcal/d), a drop that
only persisted in RYGB (-124 +/- 42 kcal/d; P = .002) and SG (-155 +/- 118
kcal/d; P = .02) groups at 1 year. The degree of metabolic adaptation (24-hour
and sleeping energy expenditure) was not significantly different between the
treatment groups at either time-point. Plasma high-density lipoprotein and total
and high molecular weight adiponectin were increased, and triglycerides and high
sensitivity C-reactive protein levels were reduced 1 year after RYGB or SG.
CONCLUSIONS: Metabolic adaptation of approximately 150 kcal/d occurs after RYGB
and SG surgery. Future studies are required to examine whether these effects
remain beyond 1 year.
PMID- 27490920
TI - Higher Prevalence of Type 2 Diabetes in Men Than in Women Is Associated With
Differences in Visceral Fat Mass.
AB - CONTEXT: We have previously found that visceral fat is a stronger predictor for
cardiovascular risk factors than body mass index (BMI). OBJECTIVE: This study
sought to investigate the prevalence of diabetes in elderly men and women in
relation to objectively assessed visceral fat volume. DESIGN AND SETTING: The
cohort consisted of a population-based sample of 705 men and 688 women, all age
70 y at the time of examination. MAIN OUTCOME MEASURES: Associations between body
fat estimates, plasma glucose level, and diabetes prevalence were investigated
using multivariable-adjusted statistical models. RESULTS: The prevalence of type
2 diabetes was 14.6% in men and 9.1% in women (P < .001). Mean BMI was slightly
higher in men than in women (27.3 vs 26.6 kg/m2; P = .01), with a greater
difference in mean visceral fat mass (1987 vs 1077 g; P < .001). After adjustment
for physical activity and smoking, men had about/approximately twice the odds of
having type 2 diabetes compared with women (odds ratio [OR], 1.95; 95% confidence
interval [CI], 1.38-2.76). The inclusion of BMI in this model did not change the
risk associated with male sex (OR, 1.93; 95% CI, 1.34-2.77). However, when
visceral fat was included as a covariate, male sex was not associated with
increased risk of type 2 diabetes (OR, 0.77; 95% CI, 0.51-1.18). CONCLUSIONS: The
higher prevalence of type 2 diabetes in older men than in older women was
associated with larger amount of visceral fat in men. In contrast, differences in
BMI was not associated with this difference.
PMID- 27490921
TI - Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a
Randomized Controlled Trial.
AB - CONTEXT: Cardiovascular risk is increased in patients with secondary adrenal
insufficiency, which may be ascribed to an unfavorable metabolic profile
consequent to a relatively high hydrocortisone replacement dose. OBJECTIVE: We
determined the effects of a higher versus a lower glucocorticoid replacement dose
on blood pressure (BP), the renin-angiotensin-aldosterone system, 11beta
hydroxysteroid dehydrogenase enzyme activity and circulating (nor)metanephrines.
DESIGN, SETTING, AND PATIENTS: Forty-seven patients with secondary adrenal
insufficiency from the University Medical Center Groningen participated in this
randomized double-blind crossover study. INTERVENTIONS: Patients randomly
received 0.2-0.3 mg hydrocortisone/kg body weight followed by 0.4-0.6 mg
hydrocortisone/kg body weight, or vice versa, each during 10 weeks. MAIN OUTCOME
MEASURE(S): BP and regulating hormones were measured. RESULTS: The higher
hydrocortisone dose resulted in an increase in systolic BP of 5 (12) mm Hg (P =
.011), diastolic BP of 2 (9) mm Hg (P = .050), and a median [interquartile range]
drop in plasma potassium of -0.1 [-0.3; 0.1] nmol/liter (P = .048). The higher
hydrocortisone dose led to decreases in serum aldosterone of -28 [-101; 9]
pmol/liter (P = .020) and plasma renin of -1.3 [-4.5; 1.2 ] pg/mL (P = .051), and
increased the ratio of plasma and urinary cortisol to cortisone (including their
metabolites) (P < .001 for all). Furthermore, on the higher dose, plasma and
urinary normetanephrine decreased by -0.101 [-0.242; 0.029] nmol/liter (P < .001)
and -1.48 [-4.06; 0.29] MUmol/mol creatinine (P < .001) respectively.
CONCLUSIONS: A higher dose of hydrocortisone increased systolic and diastolic BP
and was accompanied by changes in the renin-angiotensin-aldosterone system,
11beta-hydroxysteroid dehydrogenase enzyme activity, and circulating
normetanephrine. This demonstrates that hydrocortisone dose even within the
physiological range affects several pathways involved in BP regulation.
PMID- 27490922
TI - omega-3 Fatty Acid Ethyl Esters Diminish Postprandial Lipemia in Familial
Hypercholesterolemia.
AB - CONTEXT: Impaired postprandial chylomicron metabolism induces
hypertriglyceridemia and may increase the risk of atherosclerotic cardiovascular
disease. Omega-3 fatty acid ethyl ester (omega-3 FAEE) supplementation decreases
plasma triglycerides. However, its effect on postprandial chylomicron metabolism
in familial hypercholesterolemia (FH) has not yet been investigated. OBJECTIVE:
We aimed to examine the effect of omega-3 FAEE supplementation on postprandial
responses in plasma triglycerides, very-low-density lipoprotein (VLDL)
apolipoprotein B (apoB)-100, and apoB-48 in FH patients receiving standard
cholesterol-lowering treatment. DESIGN, SETTING, AND PATIENTS: We carried out an
8-week open-label, randomized, crossover intervention trial to test the effect of
oral supplementation with 4 g/d omega-3 FAEE (46% eicosapentaenoic acid and 38%
docosahexaenoic acid) on postprandial triglyceride, VLDL-apoB-100, and apoB-48
responses in FH patients after ingestion of an oral fat load. OUTCOMES MEASURES:
Plasma total and incremental triglyceride, VLDL-apoB-100, and apoB-48 0- to 10
hour area under the curve (AUC). RESULTS: omega-3 FAEE supplementation
significantly (P < .05 in all) reduced concentrations of fasting plasma
triglyceride (-20%), apoB (-8%), VLDL-apoB-100 (-26%), and apoB-48 (-36%); as
well as systolic blood pressure (-6%) and diastolic blood pressure (-6%).
Postprandial triglyceride and VLDL-apoB-100 total AUCs (-19% and -26%,
respectively; P < .01) and incremental AUCs (-18% and -35%, respectively; P <
.05), as well as postprandial apoB-48 total AUC (-30%; P < .02) were
significantly reduced by omega-3 FAEE supplementation. CONCLUSION:
Supplementation with omega-3 FAEEs improves postprandial lipemia in FH patients
receiving standard care; this may have implications for further reducing
atherosclerotic cardiovascular disease in this high-risk patient group.
PMID- 27490923
TI - Nanostructured Antagonist of Extrasynaptic NMDA Receptors.
AB - Glutamatergic cytotoxicity mediated by overactivation of N-methyl-d-aspartate
receptors (NMDARs) is implicated in numerous neurological disorders. To be
therapeutically viable, NMDAR antagonists must preserve physiological role of
synaptic NMDARs (sNMDARs) in synaptic transmission and block only excessive
pathological activation of NMDARs. Here we present a novel NMDAR antagonist that
satisfies this two-fold requirement by exploiting spatial differences in NMDAR
subcellular locations. Specifically, we designed a hybrid nanodrug (AuM) to be
larger than the synaptic cleft by attaching memantine, NMDAR antagonist, via
polymer linkers to a gold nanoparticle. We show that AuM efficiently and
selectively inhibited extrasynaptic NMDARs (eNMDARs), while having no effect on
sNMDARs and synaptic transmission. AuM exhibited neuroprotective properties both
in vitro and ex vivo during such neurotoxic insults as NMDAR-mediated
cytotoxicity in cerebrocortical cell culture and oxygen-glucose deprivation in
acute hippocampal slices. Furthermore, AuM prevented dendritic spine loss
triggered by Abeta oligomers in organotypic hippocampal slices and was more
effective than free memantine. Using a novel rational design strategy, we
demonstrate a proof of concept for a new class of neuroprotective drugs that
might be beneficial for treatment of several neurological disorders.
PMID- 27490925
TI - Correction: Gendist: An R Package for Generated Probability Distribution Models.
AB - [This corrects the article DOI: 10.1371/journal.pone.0156537.].
PMID- 27490924
TI - Effects of Salt Stress on Three Ecologically Distinct Plantago Species.
AB - Comparative studies on the responses to salt stress of taxonomically related taxa
should help to elucidate relevant mechanisms of stress tolerance in plants. We
have applied this strategy to three Plantago species adapted to different natural
habitats, P. crassifolia and P. coronopus-both halophytes-and P. major,
considered as salt-sensitive since it is never found in natural saline habitats.
Growth inhibition measurements in controlled salt treatments indicated, however,
that P. major is quite resistant to salt stress, although less than its
halophytic congeners. The contents of monovalent ions and specific osmolytes were
determined in plant leaves after four-week salt treatments. Salt-treated plants
of the three taxa accumulated Na+ and Cl- in response to increasing external NaCl
concentrations, to a lesser extent in P. major than in the halophytes; the latter
species also showed higher ion contents in the non-stressed plants. In the
halophytes, K+ concentration decreased at moderate salinity levels, to increase
again under high salt conditions, whereas in P. major K+ contents were reduced
only above 400 mM NaCl. Sorbitol contents augmented in all plants, roughly in
parallel with increasing salinity, but the relative increments and the absolute
values reached did not differ much in the three taxa. On the contrary, a strong
(relative) accumulation of proline in response to high salt concentrations (600
800 mM NaCl) was observed in the halophytes, but not in P. major. These results
indicate that the responses to salt stress triggered specifically in the
halophytes, and therefore the most relevant for tolerance in the genus Plantago
are: a higher efficiency in the transport of toxic ions to the leaves, the
capacity to use inorganic ions as osmotica, even under low salinity conditions,
and the activation, in response to very high salt concentrations, of proline
accumulation and K+ transport to the leaves of the plants.
PMID- 27490926
TI - Transgelin is a TGFbeta-inducible gene that regulates osteoblastic and adipogenic
differentiation of human skeletal stem cells through actin cytoskeleston
organization.
AB - Regenerative medicine is a novel approach for treating conditions in which
enhanced bone regeneration is required. We identified transgelin (TAGLN), a
transforming growth factor beta (TGFbeta)-inducible gene, as an upregulated gene
during in vitro osteoblastic and adipocytic differentiation of human bone marrow
derived stromal (skeletal) stem cells (hMSC). siRNA-mediated gene silencing of
TAGLN impaired lineage differentiation into osteoblasts and adipocytes but
enhanced cell proliferation. Additional functional studies revealed that TAGLN
deficiency impaired hMSC cell motility and in vitro transwell cell migration. On
the other hand, TAGLN overexpression reduced hMSC cell proliferation, but
enhanced cell migration, osteoblastic and adipocytic differentiation, and in vivo
bone formation. In addition, deficiency or overexpression of TAGLN in hMSC was
associated with significant changes in cellular and nuclear morphology and
cytoplasmic organelle composition as demonstrated by high content imaging and
transmission electron microscopy that revealed pronounced alterations in the
distribution of the actin filament and changes in cytoskeletal organization.
Molecular signature of TAGLN-deficient hMSC showed that several genes and genetic
pathways associated with cell differentiation, including regulation of actin
cytoskeleton and focal adhesion pathways, were downregulated. Our data
demonstrate that TAGLN has a role in generating committed progenitor cells from
undifferentiated hMSC by regulating cytoskeleton organization. Targeting TAGLN is
a plausible approach to enrich for committed hMSC cells needed for regenerative
medicine application.
PMID- 27490927
TI - TLR and NLRP3 inflammasome-dependent innate immune responses to tumor-derived
autophagosomes (DRibbles).
AB - Autophagosomes derived from tumor cells, also referred to as defective ribosomal
products in blebs (DRibbles), have been previously shown to stimulate potent T
cell responses and mediate tumor regression when used as therapeutic cancer
vaccines in multiple preclinical cancer models. In this report, we investigated
the underlining mechanisms by which DRibbles induced T-cell activation,
particularly how DRibbles activated antigen-presenting cells (APCs). We found
that DRibbles could induce a rapid differentiation of monocytes and DC precursor
(pre-DC) cells into functional APCs. DRibbles triggered innate receptor signaling
via Toll-like Receptors (TLR)-2, TLR4, TLR7, TLR8, and nucleotide-binding
oligomerization domain-containing protein 2 (NOD2), but not TLR3, TLR5, or TLR9.
DRibbles induced PBMCs to produce pro-inflammatory cytokines, such as IL-6, IL
10, TNF-alpha, and IL-1beta. DRibbles induced IL-1beta release from PBMC or THP-1
cells without LPS priming, but required the core machinery of NLRP3
inflammasomes. Active endocytosis was required for inflammasome activation and
cross presentation, and blocking endosome acidification or the ER-associated
degradation (ERAD) pathway resulted in opposite effects on these two processes.
Our data show that DRibbles could induce strong innate immune responses via
multiple pattern recognition receptors, and explain why DRibbles could function
as excellent antigen carriers to induce adaptive immune responses to both tumor
cells and viruses. In contrast to the well-established inhibitory effect of
autophagy on the inflammasome activation of APCs, our study demonstrates that
isolated autophagosomes (DRibbles) from antigen donor cells activate
inflammasomes by providing first and second signals required for IL-1beta
production by PMBC.
PMID- 27490928
TI - TMEM166/EVA1A interacts with ATG16L1 and induces autophagosome formation and cell
death.
AB - The formation of the autophagosome is controlled by an orderly action of ATG
proteins. However, how these proteins are recruited to autophagic membranes
remain poorly clarified. In this study, we have provided a line of evidence
confirming that EVA1A (eva-1 homolog A)/TMEM166 (transmembrane protein 166) is
associated with autophagosomal membrane development. This notion is based on
dotted EVA1A structures that colocalize with ZFYVE1, ATG9, LC3B, ATG16L1, ATG5,
STX17, RAB7 and LAMP1, which represent different stages of the autophagic
process. It is required for autophagosome formation as this phenotype was
significantly decreased in EVA1A-silenced cells and Eva1a KO MEFs. EVA1A-induced
autophagy is independent of the BECN1-PIK3C3 (phosphatidylinositol 3-kinase,
catalytic subunit type 3) complex but requires ATG7 activity and the ATG12
ATG5/ATG16L1 complex. Here, we present a molecular mechanism by which EVA1A
interacts with the WD repeats of ATG16L1 through its C-terminal and promotes
ATG12-ATG5/ATG16L1 complex recruitment to the autophagic membrane and enhances
the formation of the autophagosome. We also found that both autophagic and
apoptotic mechanisms contributed to EVA1A-induced cell death while inhibition of
autophagy and apoptosis attenuated EVA1A-induced cell death. Overall, these
findings provide a comprehensive view to our understanding of the pathways
involved in the role of EVA1A in autophagy and programmed cell death.
PMID- 27490931
TI - The Medical and Surgical Treatment of ARCO Stage-I and II Osteonecrosis of the
Femoral Head: A Critical Analysis Review.
PMID- 27490929
TI - Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in
hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway.
AB - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death
worldwide, and systemic chemotherapy is the major treatment strategy for late
stage HCC patients. Poor prognosis following chemotherapy is the general outcome
owing to recurrent resistance. Recent studies have suggested that in addition to
cytotoxic effects on tumor cells, chemotherapy can induce an alternative cascade
that supports tumor growth and metastasis. In the present investigation, we
showed that thyroid hormone (TH), a potent hormone-mediating cellular
differentiation and metabolism, acts as an antiapoptosis factor upon challenge of
thyroid hormone receptor (TR)-expressing HCC cells with cancer therapy drugs,
including cisplatin, doxorubicin and tumor necrosis factor-related apoptosis
inducing ligand (TRAIL). TH/TR signaling promoted chemotherapy resistance through
negatively regulating the pro-apoptotic protein, Bim, resulting in doxorubicin
induced metastasis of chemotherapy-resistant HCC cells. Ectopic expression of Bim
in hepatoma cells challenged with chemotherapeutic drugs abolished TH/TR
triggered apoptosis resistance and metastasis. Furthermore, Bim expression was
directly transactivated by Forkhead box protein O1 (FoxO1), which was negatively
regulated by TH/TR. TH/TR suppressed FoxO1 activity through both transcriptional
downregulation and nuclear exclusion of FoxO1 triggered by Akt-mediated
phosphorylation. Ectopic expression of the constitutively active FoxO1 mutant,
FoxO1-AAA, but not FoxO1-wt, diminished the suppressive effect of TH/TR on Bim.
Our findings collectively suggest that expression of Bim is mediated by FoxO1 and
indirectly downregulated by TH/TR, leading to chemotherapy resistance and
doxorubicin-promoted metastasis of hepatoma cells.
PMID- 27490932
TI - Coracoid Process Transfer for Recurrent Instability of the Shoulder: A Critical
Analysis Review.
PMID- 27490930
TI - Inhibitor of apoptosis protein expression in glioblastomas and their in vitro and
in vivo targeting by SMAC mimetic GDC-0152.
AB - Glioblastomas (GBMs) are the most aggressive primary brain tumors in adult and
remain a therapeutic challenge. Targeting key apoptosis regulators with the
ultimate aim to restore apoptosis in tumor cells could be an interesting
therapeutic strategy. The inhibitors of apoptosis proteins (IAPs) are regulators
of cell death and represent attractive targets, especially because they can be
antagonized by SMAC mimetics. In this study, we first investigated the expression
of cIAP1, cIAP2, XIAP and ML-IAP in human GBM samples and in four different cell
lines. We showed that all GBM samples and GBM cell lines expressed all these
IAPs, although the expression of each IAP varied from one case to another. We
then showed that high level of ML-IAP predicted worse progression-free survival
and overall survival in both univariate and multivariate analyses in two
independent cohorts of 58 and 43 primary human GBMs. We then used GDC-0152, a
SMAC mimetic that antagonizes these IAPs and confirmed that GDC-0152 treatment in
vitro decreased IAPs in all the cell lines studied. It affected cell line
viability and triggered apoptosis, although the effect was higher in U87MG and
GL261 than in GBM6 and GBM9 cell lines. In vivo, GDC-0152 effect on U87MG
orthotopic xenografts was dose dependent; it postponed tumor formation and slowed
down tumor growth, significantly improving survival of GBM-bearing mice. This
study revealed for the first time that ML-IAP protein expression correlates with
GBM patient survival and that its antagonist GDC-0152 improves outcome in
xenografted mouse.
PMID- 27490933
TI - Use of Irradiated and Non-Irradiated Allograft Tissue in Anterior Cruciate
Ligament Reconstruction Surgery: A Critical Analysis Review.
PMID- 27490934
TI - Metal Hypersensitivity in Patients with Conventional Orthopaedic Implants.
PMID- 27490935
TI - Conjoint FTLD-FUS of the neuronal intermediate filament inclusion disease type,
progressive supranuclear palsy and Alzheimer's pathology presenting as
parkinsonism with early falls and late hallucinations, psychosis and dementia.
PMID- 27490936
TI - Determination of Ginkgolides A, B, C, J and Bilobalide in Plasma by LC-ESI (
)/MS/MS (QQQ) and its Application to the Pharmacokinetic Study of Ginkgo Biloba
Extract in Rats.
AB - A simple, rapid, and specific high-performance liquid chromatograph coupled with
a tandem mass spectrometry method has been developed and validated for the
quantification of ginkgolides in rat plasma, and the main pharmacokinetic
parameters of ginkgolides after oral administration of Ginkgo biloba extract
(GBE) was acquired. Methods: Plasma samples were pretreated with ethyl acetate
extraction. Sulfamethoxazole was used as the internal standard (IS).
Chromatographic separation was achieved on an Eclipse XDB-C18 column (2.1 mm*150
mm, 5 MUm) with a mobile phase consisting of methanol/0.1% formic acid water
(gradient elution: 0~25 min (77:23)->(60:40), V/V) at a flow rate of 0.3 mL.min
1. The detection was performed on a triple quadruple tandem mass spectrometer
using an electrospray ionization (ESI) source for 25 min. The detection was
operated by multiple reaction monitoring(MRM) under negative ionization mode of
the transitions of m/z 325->163 for BB, 469->423 for GJ, 439->125 for GC, 453
>351 for GA, 423->367 for GB and of m/z 252->156 for sulfamethoxazole (IS)
respectively. Results: The pharmacokinetic properties of BB, GJ, GA, GB and GC
were in line with the open 2-compartment model after oral administration of GBE
in rats; The pharmacokinetic parameters of various lactones were calculated, and
drugs-time curve and the curve fitting diagram of 5 ginkgolides were drew; The
absorption and distribution rate of BB, GJ, GA, GB and GC were fast in rats in
vivo, and half-life of absorption was less than 3 h. Conclusion: The developed LC
ESI (-)/MS/MS (QQQ) method was successfully applied to assess the pharmacokinetic
parameters and oral bioavailability of ginkgolides in rats after administration
of GBE, which can provide basis for further clinical efficacy studies.
PMID- 27490937
TI - Predictions of the Pharmacokinetics in Burn Injury Patients using Regression
Models - Case Study with Levofloxacin.
AB - Owing to its excellent safety, tolerability, pharmacokinetic and pharmacodynamic
profile levofloxacin is widely used. Although pharmacokinetics of levofloxacin
was somewhat more variable in burn injury patients, it appeared to be comparable
to healthy subjects or other patients. Linear regression model was established
for Cmax or Cmin vs. [AUCtau, CL and Vd] of levofloxacin using individual values
from burn injury patients. Appropriate regression lines for Cmax or Cmin were
subjected to internal and external validation on the ability to predict CL, Vd
and AUCtau parameters. The mean absolute error (MAE) and root mean square error
(RMSE) of the predictions were used to judge the appropriateness of either Cmax
or Cmin models. Cmax models developed for levofloxacin showed moderate to strong
correlations with the various parameters such as CL, Vd and AUCtau. The Cmin
models showed strong correlation for CL and AUCtau but not for Vd where the
correlation was weak. Internal validation using data from individual burn
patients showed RMSE of 13.47-25.42% for various predictions. External validation
that used mean data from healthy subjects showed RMSE of 13.86-27.13%. Despite
the pharmacokinetic variability, linear regression models using either Cmax or
Cmin were established for levofloxacin rendering predictions of several key
pharmacokinetic parameters. Although there was limitation of Cmin model for
predicting Vd, both models may be used as a prospective tool for the prediction
of levofloxacin pharmacokinetics in burn care patients.
PMID- 27490938
TI - A Tightly Stretched Ultralong Supramolecular Multiporphyrin Array Propagated by
Double-Strand Formation.
AB - A shape-programmed linearity through supramolecular polymerization is
demonstrated by a step-growth double-strand formation of a telechelic oligomeric
porphyrin array in which two alternating pyridyl-porphyrin sequenced units are
held together by self-complementary ligand-to-metal coordination. The stiff rod
like structure and sufficiently large binding constant of the double-strand unit
considerably extended a supramolecular array in the one dimension, which produced
a tightly stretched string with a length that exceeded several micrometers.
PMID- 27490939
TI - The in vitro generation of multi-tumor antigen-specific cytotoxic T cell clones:
Candidates for leukemia adoptive immunotherapy following allogeneic stem cell
transplantation.
AB - Adoptive T-cell immunotherapy is a promising approach to manage and maintain
relapse-free survival of leukemia patients, especially following allogeneic stem
cell transplantation. Post-transplant adoptive immunotherapy using cytotoxic T
lymphocytes (CTLs) of the donor origin provide graft-versus-tumor effects, with
or without graft-versus-host disease. Myeloid leukemias express immunogenic
leukemia associated antigens (LAAs); such as WT-1, PRAME, MAGE, h-TERT and
others, most of them are able to induce specific T cell responses whenever
associated with the proper co-stimulation. We investigated the ability of a LAA
expressing hybridoma cell line to induce CTL clones in PBMCs of HLA-matched
healthy donors in vitro. The CTL clones were induced by repetitive co-culture
with LAAs-expressing, HLA-A*0201(+) hybrid cell line, generated by fusion of
leukemia blasts to human immortalized APC (EBV-sensitized B-lymphoblastoid cell
line; HMy2). The induced cytotoxic T cell clones were phenotypically and
functionally characterized by pentamer analysis, IFN-gamma release ELISPOT and
cellular cytotoxicity assays. All T cell lines showed robust peptide recognition
and functional activity when sensitized with HLA-A*0201-restricted WT-1235-243,
hTERT615-624 or PRAME100-108 peptides-pulsed T2 cells, in addition to partially
HLA-matched leukemia blasts. This study demonstrates the feasibility of
developing multi-tumor antigen-specific T cell lines in allogeneic PBMCs in
vitro, using LAA-expressing tumor/HMy2 hybrid cell line model, for potential use
in leukemia adoptive immunotherapy in partially matched donor-recipient setting.
PMID- 27490940
TI - Familial C3 glomerulonephritis caused by a novel CFHR5-CFHR2 fusion gene.
AB - C3 glomerulopathy (C3G) is an ultra-rare complement-mediated renal disease
characterized histologically by the predominance of C3 deposition within in the
glomerulus. Familial cases of C3G are extremely uncommon and offer unique insight
into the genetic drivers of complement dysregulation. In this report, we describe
a patient who presented with C3G. Because a relative carried the same diagnosis,
we sought an underlying genetic commonality to explain the phenotype. As part of
a comprehension genetic screen, we completed multiplex ligation-dependent probe
amplification across the complement factor H related region and identified
amplification alterations consistent with a genomic rearrangement. Using
comparative genomic hybridization, we narrowed and then cloned the rearrangement
breakpoints thereby defining a novel fusion gene that is translated into a serum
protein comprised of factor H related-5 (short consensus repeats 1 and 2) and
factor H-related-2 (short consensus repeats 1-4). These data highlight the role
of factor H related proteins in the control of complement activity and illustrate
how perturbation of that control leads to C3G.
PMID- 27490941
TI - Diagnostic Accuracy of CT for Local Staging of Colon Cancer: A Systematic Review
and Meta-Analysis.
AB - OBJECTIVE: The purpose of this article is to determine the accuracy of CT in the
detection of tumor invasion beyond the bowel wall and nodal involvement of colon
carcinomas. A literature search was performed to identify studies describing the
accuracy of CT in the staging of colon carcinomas. Studies including rectal
carcinomas that were inseparable from colon carcinomas were excluded. Publication
bias was explored by using a Deeks funnel plot asymmetry test. A hierarchic
summary ROC model was used to construct a summary ROC curve and to calculate
summary estimates of sensitivity, specificity, and diagnostic odds ratios (ORs).
CONCLUSION: On the basis of a total of 13 studies, pooled sensitivity,
specificity, and diagnostic ORs for detection of tumor invasion beyond the bowel
wall (T3-T4) were 90% (95% CI, 83-95%), 69% (95% CI, 62-75%), and 20.6 (95% CI,
10.2-41.5), respectively. For detection of tumor invasion depth of 5 mm or
greater (T3cd-T4), estimates from four studies were 77% (95% CI, 66-85%), 70%
(95% CI, 53-83%), and 7.8 (95% CI, 4.2-14.2), respectively. For nodal involvement
(N+), 16 studies were included with values of 71% (95% CI, 59-81%), 67% (95% CI,
46-83%), and 4.8 (95% CI, 2.5-9.4), respectively. Two studies using CT
colonography were included with sensitivity and specificity of 97% (95% CI, 90
99%) and 81% (95% CI, 65-91%), respectively, for detecting T3-T4 tumors. CT has
good sensitivity for the detection of T3-T4 tumors, and evidence suggests that CT
colonography increases its accuracy. Discriminating between T1-T3ab and T3cd-T4
cancer is challenging, but data were limited. CT has a low accuracy in detecting
nodal involvement.
PMID- 27490943
TI - Effect of light exposure on linalool biosynthesis and accumulation in grape
berries.
AB - Linalool is an important compound that contributes to the floral aroma in wines.
This study showed the effect of light exposure on linalool accumulation in
berries. The grape bunches were covered with films that block the full light
spectrum (Shade) and the UV spectrum (UV-block), and a transparent film
(Control). The linalool content was significantly higher in juice from Control
covered berries than in juice from Shade- and UV-block-covered berries, and the
expression levels of the representative genes in linalool biosynthesis in Shade-
and UV-block-covered berries were markedly lower than in Control-covered berries.
These findings suggest that exposing berries to light is essential for linalool
biosynthesis. To reflect sunlight onto grape clusters, reflective sheets were
placed on the ground of a vineyard. The linalool content in berries exposed to
sunlight reflected from the reflective sheets was higher than those in the
control.
PMID- 27490942
TI - Solid-Vapor Reaction Growth of Transition-Metal Dichalcogenide Monolayers.
AB - Two-dimensional (2D) layered semiconducting transition-metal dichalcogenides
(TMDCs) are promising candidates for next-generation ultrathin, flexible, and
transparent electronics. Chemical vapor deposition (CVD) is a promising method
for their controllable, scalable synthesis but the growth mechanism is poorly
understood. Herein, we present systematic studies to understand the CVD growth
mechanism of monolayer MoSe2 , showing reaction pathways for growth from solid
and vapor precursors. Examination of metastable nanoparticles deposited on the
substrate during growth shows intermediate growth stages and conversion of non
stoichiometric nanoparticles into stoichiometric 2D MoSe2 monolayers. The growth
steps involve the evaporation and reduction of MoO3 solid precursors to sub
oxides and stepwise reactions with Se vapor to finally form MoSe2 . The
experimental results and proposed model were corroborated by ab initio Car
Parrinello molecular dynamics studies.
PMID- 27490944
TI - Cortical blindness post coronary angiogram: A rare but frightening complication.
AB - Cortical blindness is a rare but frightening complication following coronary
angiogram probably due to contrast penetration in occipital lobes in susceptible
individuals [1, 2].
PMID- 27490945
TI - Multiclass method for the determination of 62 antibiotics in milk.
AB - A multiclass method for screening and confirmatory analysis of antimicrobial
residues in milk has been developed and validated. Sixty-two antibiotics
belonging to ten different drug families (amphenicols, cephalosporins,
lincosamides, macrolides, penicillin, pleuromutilins, quinolones, rifamycins,
sulfonamides and tetracyclines) have been included. After the addition of an
aqueous solution of EDTA, the milk samples were extracted twice with
acetonitrile, evaporated and dissolved in ammonium acetate. After centrifugation,
10 ul were analysed using LC-Q-Orbitrap operating in positive electrospray
ionization mode. The method was validated in bovine milk in the range 2-150 ug
kg(-1) for all antibiotics; for four compounds with maximum residue limits higher
than 100 ug kg(-1) , the validation interval has been extended until 333 ug kg(
1) . The estimated performance characteristics were satisfactory complying with
the requirements of Commission Decision 2002/657/EC. Good accuracies were
obtained also taking advantage from the versatility of the hybrid mass analyser.
Identification criteria were achieved verifying the mass accuracy and ion ratio
of two ions, including the pseudomolecular one, where possible. Finally, the
developed procedure was applied to 13 real cases of suspect milk samples
(microbiological assay) confirming the presence of one or more antibiotics,
although frequently, the maximum residue limits were not exceeded. The
availability of rapid multiclass confirmatory methods can avoid wastes of
suspect, but compliant, raw milk samples. Copyright (c) 2016 John Wiley & Sons,
Ltd.
PMID- 27490946
TI - Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort
Suggests Population-Specific Associations of Rare Variants in MUC2.
AB - Genome-wide association studies have revealed several common genetic risk
variants for ulcerative colitis (UC). However, little is known about the
contribution of rare, large effect genetic variants to UC susceptibility. In this
study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC
patients in order to investigate the contribution of rare variants to the genetic
susceptibility to UC. The selection of genes consists of 111 established human UC
susceptibility genes and 11 genes that lead to spontaneous colitis when knocked
out in mice. In addition, we sequenced the promoter regions of 45 genes where
known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was
performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project
provided sequence data of 500 healthy controls. After quality control and
prioritization based on allele frequency and pathogenicity probability, follow-up
genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166
Dutch controls. Single-variant association and gene-based analyses identified an
association of rare variants in the MUC2 gene with UC. The associated variants in
the Dutch population could not be replicated in a German replication cohort (1026
UC cases, 3532 controls). In conclusion, this study has identified a putative
role for MUC2 on UC susceptibility in the Dutch population and suggests a
population-specific contribution of rare variants to UC.
PMID- 27490947
TI - Mirror-Touch Synaesthesia Is Not Associated with Heightened Empathy, and Can
Occur with Autism.
AB - Research has linked Mirror-Touch (MT) synaesthesia with enhanced empathy. We test
the largest sample of MT synaesthetes to date to examine two claims that have
been previously made: that MT synaesthetes (1) have superior empathy; and (2)
only ever experience their MT synaesthesia in response to viewing a person being
touched. Given that autism has been suggested to involve deficits in cognitive
empathy, we also test two predictions: that MT synaesthetes should (3) be less
likely than general population individuals without MT synaesthesia to have an
autism spectrum condition (ASC), if MT is characterized by superior empathy; and
(4) have fewer autistic traits. We selected three groups: a pure MT synaesthesia
group (N = 46), a pure grapheme-colour (GC) synaesthesia group (N = 36), and a
typical control group without synaesthesia (N = 46). Participants took three
measures of empathy and one measure of autistic traits. MT synaesthetes did not
show enhanced empathy. In addition, 30% of all MT synaesthetes recruited into
this study (N = 135) reported also having ASC, and MT synaesthetes showed higher
autistic trait scores than controls. Finally, some MT experiences were reported
in response to viewing objects being touched. Our findings dispute the views that
MT synaesthesia is linked with enhanced empathy, is less likely to occur with ASC
or elevated autistic traits, and is specific to seeing a person being touched.
PMID- 27490948
TI - A Single-Flask Synthesis of Morita-Baylis-Hillman Adducts from Ethoxyacetylene
and Carbonyl Compounds: Synthesis of Subamolides D and E.
AB - Sequential treatment of (ethoxyethynyl)lithium with aldehydes and/or ketones (2
and 4) and BF3.OEt2 gives rise to beta-hydroxyenoates 5 in good to excellent
overall yields. Similarly, the combination of 1 (M = Li) and dicarbonyl compounds
6 (X = O) or keto/aldehyde acetals (X = OMe) followed by the addition of a Lewis
acid leads to five-, six-, and seven-membered hydroxycycloalkene carboxyates. The
utility of this method is demonstrated in the synthesis of the alpha-alkylidene
lactone natural products subamolide D and E.
PMID- 27490951
TI - Feasibility and reliability of carotid intima-media thickness measurements in
nonsedated infants.
AB - INTRODUCTION: Carotid intima-media thickness (CIMT) is a surrogate marker for
atherosclerosis. It is increased in adolescents and young adults at risk for
future cardiovascular disease. However, it remains unclear if it can be
considered as a surrogate marker for atherosclerosis in infancy as very few
studies have been performed in infants. OBJECTIVES: Our objective was to assess
the feasibility and interobserver reproducibility of CIMT measurement in
nonsedated infants. METHODS: We measured CIMT in 81 infants less than 1 year of
age. Repeated measurements were obtained by a second observer in 24 children. The
analysis was performed with semiautomated edge detection software. Measurements
with over 95% edge detection over a length of 1 cm were considered as valid. We
further compared the measurements using the semiautomated method with
measurements using the manual electronic caliper method in a subgroup of 10
infants. RESULTS: Carotid ultrasound recordings and intima-media thickness
measurements were obtained in 79% of infants (n = 64). Mean CIMT of the 64
infants measured by the first observer was 0.44 mm (SD: 0.04). In the 24
participants with measurements by two observers, the mean interobserver
difference was 0.001 mm (SD: 0.026). The interobserver coefficient of variation
was 5.9%. CIMT measurements obtained with the manual method (mean: 0.35; range:
0.29-0.39) were slightly lower than measurements obtained with the semiautomated
method (mean: 0.38; range: 0.32-0.44). Measurements with both methods were highly
correlated (r: 0.87). CONCLUSION: Measurement of CIMT in nonsedated infants less
than 1 year of age is feasible in the majority of infants with good interobserver
variability.
PMID- 27490950
TI - Can arterial wave augmentation in young adults help account for variability of
cardiovascular risk in different British ethnic groups?
AB - OBJECTIVE: Traditional cardiovascular risk factors do not fully account for
ethnic differences in cardiovascular disease. We tested if arterial function
indices, particularly augmentation index (AIx), and their determinants from
childhood could underlie such ethnic variability among young British adults in
the 'DASH' longitudinal study. METHODS: DASH, at http://dash.sphsu.mrc.ac.uk/,
includes representative samples of six main British ethnic groups. Pulse wave
velocity (PWV) and AIx were recorded using the Arteriograph device at ages 21-23
years in a subsample (n = 666); psychosocial, anthropometric, and blood pressure
(BP) measures were collected then and in two previous surveys at ages 11-13 years
and 14-16 years. For n = 334, physical activity was measured over 5 days
(ActivPal). RESULTS: Unadjusted values and regression models for PWVs were
similar or lower in ethnic minority than in White UK young adults, whereas AIx
was higher - Caribbean (14.9, 95% confidence interval 12.3-17.0%), West African
(15.3, 12.9-17.7%), Indian (15.1, 13.0-17.2%), and Pakistani/Bangladeshi (15.7,
13.7-17.7%), compared with White UK (11.9, 10.2-13.6%). In multivariate models,
adjusted for sex, central SBP, height, and heart rate, Indian and
Pakistani/Bangladeshi young adults had higher AIx (beta = 3.35, 4.20,
respectively, P < 0.01) than White UK with a similar trend for West Africans and
Caribbeans but not statistically significant. Unlike PWV, physical activity,
psychosocial or deprivation measures were not associated with AIx, with
borderline associations from brachial BP but no other childhood variables.
CONCLUSION: Early adult AIx, but not arterial stiffness, may be a useful tool for
testing components of excess cardiovascular risk in some ethnic minority groups.
PMID- 27490949
TI - Cholinergic profiles in the Goettingen miniature pig (Sus scrofa domesticus)
brain.
AB - Central cholinergic structures within the brain of the even-toed hoofed
Goettingen miniature domestic pig (Sus scrofa domesticus) were evaluated by
immunohistochemical visualization of choline acetyltransferase (ChAT) and the low
affinity neurotrophin receptor, p75NTR . ChAT-immunoreactive (-ir) perikarya were
seen in the olfactory tubercle, striatum, medial septal nucleus, vertical and
horizontal limbs of the diagonal band of Broca, and the nucleus basalis of
Meynert, medial habenular nucleus, zona incerta, neurosecretory arcuate nucleus,
cranial motor nuclei III and IV, Edinger-Westphal nucleus, parabigeminal nucleus,
pedunculopontine nucleus, and laterodorsal tegmental nucleus. Cholinergic ChAT-ir
neurons were also found within transitional cortical areas (insular, cingulate,
and piriform cortices) and hippocampus proper. ChAT-ir fibers were seen
throughout the dentate gyrus and hippocampus, in the mediodorsal, laterodorsal,
anteroventral, and parateanial thalamic nuclei, the fasciculus retroflexus of
Meynert, basolateral and basomedial amygdaloid nuclei, anterior pretectal and
interpeduncular nuclei, as well as select laminae of the superior colliculus.
Double immunofluorescence demonstrated that virtually all ChAT-ir basal forebrain
neurons were also p75NTR -positive. The present findings indicate that the
central cholinergic system in the miniature pig is similar to other mammalian
species. Therefore, the miniature pig may be an appropriate animal model for
preclinical studies of neurodegenerative diseases where the cholinergic system is
compromised. J. Comp. Neurol. 525:553-573, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490952
TI - Significance of masked and nocturnal hypertension in normotensive women coursing
a high-risk pregnancy.
AB - OBJECTIVE: The aim was to evaluate the prevalence of nocturnal and masked
hypertension and the prognostic values of these blood pressure (BP) abnormalities
in normotensive women coursing a high-risk pregnancy. METHODS: The study was
performed in pregnant women with 20 or more weeks of gestation coursing a high
risk pregnancy, sent to a specialized hypertension department to perform a
prospective defined protocol of BP evaluation. Women with office BP at least
140/90 mmHg were excluded. An ambulatory monitoring of BP was performed to
identify masked and nocturnal hypertension (defined according to the current
guidelines). The adjusted risk for development of preeclampsia/eclampsia (PEEC)
was estimated using logistic regression. The ability of SBP and DBP to identify
risk of PEEC was estimated using area under the receiver-operating characteristic
curves. RESULTS: Eighty-seven women (29 +/- 7 years old, 30 +/- 5 weeks of
pregnancy) were included in this analysis. The prevalence of masked hypertension
was 33.3%. Nocturnal hypertension was found in 42.5% of the women. Remarkably,
27.0% of the women with nocturnal hypertension had normal 24-h values according
to ambulatory BP monitoring. Twenty-two patients developed PEEC; adjusted
relative risks increased with the presence of nocturnal (odds ratio = 4.72, 95%
confidence interval 1.25-19.43, P = 0.023) or masked hypertension (odds ratio =
7.81, 95% confidence interval 2.6-22.86, P = 0.001). Nocturnal SBP and DBP had
the highest abilities to predict PEEC (area under the curve = 0.77 and 0.80,
respectively). CONCLUSION: Masked and nocturnal hypertension are frequent
findings in normotensive women coursing a high-risk pregnancy, and their presence
implies an increased risk to develop PEEC.
PMID- 27490954
TI - A double-mutant collection targeting MAP kinase related genes in Arabidopsis for
studying genetic interactions.
AB - Mitogen-activated protein kinase cascades are conserved in all eukaryotes. In
Arabidopsis thaliana there are approximately 80 genes encoding MAP kinase kinase
kinases (MAP3K), 10 genes encoding MAP kinase kinases (MAP2K), and 20 genes
encoding MAP kinases (MAPK). Reverse genetic analysis has failed to reveal
abnormal phenotypes for a majority of these genes. One strategy for uncovering
gene function when single-mutant lines do not produce an informative phenotype is
to perform a systematic genetic interaction screen whereby double-mutants are
created from a large library of single-mutant lines. Here we describe a new
collection of 275 double-mutant lines derived from a library of single-mutants
targeting genes related to MAP kinase signaling. To facilitate this study, we
developed a high-throughput double-mutant generating pipeline using a system for
growing Arabidopsis seedlings in 96-well plates. A quantitative root growth assay
was used to screen for evidence of genetic interactions in this double-mutant
collection. Our screen revealed four genetic interactions, all of which caused
synthetic enhancement of the root growth defects observed in a MAP kinase 4
(MPK4) single-mutant line. Seeds for this double-mutant collection are publicly
available through the Arabidopsis Biological Resource Center. Scientists
interested in diverse biological processes can now screen this double-mutant
collection under a wide range of growth conditions in order to search for
additional genetic interactions that may provide new insights into MAP kinase
signaling.
PMID- 27490955
TI - Microbiota Characterization of Compost Using Omics Approaches Opens New
Perspectives for Phytophthora Root Rot Control.
AB - Phytophthora root rot caused by Phytophthora nicotianae is an economically
important disease in pepper crops. The use of suppressive composts is a low
environmental impact method for its control. Although attempts have been made to
reveal the relationship between microbiota and compost suppressiveness, little is
known about the microorganisms associated with disease suppression. Here, an Ion
Torrent platform was used to assess the microbial composition of composts made of
different agro-industrial waste and with different levels of suppressiveness
against P. nicotianae. Both bacterial and fungal populations responded
differently depending on the chemical heterogeneity of materials used during the
composting process. High proportions (67-75%) of vineyard pruning waste were used
in the most suppressive composts, COM-A and COM-B. This material may have
promoted the presence of higher relative abundance of Ascomycota as well as
higher microbial activity, which have proved to be essential for controlling the
disease. Although no unique fungi or bacteria have been detected in neither
suppressive nor conducive composts, relatively high abundance of Fusarium and
Zopfiella were found in compost COM-B and COM-A, respectively. To the best of our
knowledge, this is the first work that studies compost metabolome. Surprisingly,
composts and peat clustered together in principal component analysis of the
metabolic data according to their levels of suppressiveness achieved. This study
demonstrated the need for combining the information provided by different
techniques, including metagenomics and metametabolomics, to better understand the
ability of compost to control plant diseases.
PMID- 27490956
TI - Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8
Inhibitors Discovered by High-Throughput Screening.
AB - The mediator complex-associated cyclin dependent kinase CDK8 regulates beta
catenin-dependent transcription following activation of WNT signaling. Multiple
lines of evidence suggest CDK8 may act as an oncogene in the development of
colorectal cancer. Here we describe the successful optimization of an imidazo
thiadiazole series of CDK8 inhibitors that was identified in a high-throughput
screening campaign and further progressed by structure-based design. In several
optimization cycles, we improved the microsomal stability, potency, and kinase
selectivity. The initial imidazo-thiadiazole scaffold was replaced by a 3-methyl
1H-pyrazolo[3,4-b]-pyridine which resulted in compound 25 (MSC2530818) that
displayed excellent kinase selectivity, biochemical and cellular potency,
microsomal stability, and is orally bioavailable. Furthermore, we demonstrated
modulation of phospho-STAT1, a pharmacodynamic biomarker of CDK8 activity, and
tumor growth inhibition in an APC mutant SW620 human colorectal carcinoma
xenograft model after oral administration. Compound 25 demonstrated suitable
potency and selectivity to progress into preclinical in vivo efficacy and safety
studies.
PMID- 27490957
TI - Fragility Fracture Incidence in Chronic Obstructive Pulmonary Disease (COPD)
Patients Associates With Nanoporosity, Mineral/Matrix Ratio, and Pyridinoline
Content at Actively Bone-Forming Trabecular Surfaces.
AB - Chronic obstructive pulmonary disease (COPD) is associated with low areal bone
mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) and altered
microstructure by bone histomorphometry and micro-computed tomography.
Nevertheless, not all COPD patients sustain fragility fractures. In the present
study, we used Raman microspectroscopic analysis to determine bone compositional
properties at actively forming trabecular surfaces (based on double fluorescent
labels) in iliac crest biopsies from 19 postmenopausal COPD patients (aged 62.1
+/- 7.3 years). Additionally, we analyzed trabecular geometrical centers,
representing tissue much older than the forming surfaces. Eight of the patients
had sustained fragility fractures, and 13 had received treatment with inhaled
glucocorticoids. None of the patients had taken oral glucocorticoids. The
monitored parameters were mineral/matrix ratio (MM), nanoporosity, and relative
glycosaminoglycan (GAG), lipid, and pyridinoline contents (PYD). There were no
significant differences between the glucocorticoid-treated patients and those who
did not receive any. On the other hand, COPD patients sustaining fragility
fractures had significantly lower nanoporosity and higher MM and PYD values
compared with COPD patients without fragility fractures. To the best of our
knowledge, this is the first study to discriminate between fracture and non
fracture COPD patients based on differences in the material properties of bone
matrix. Given that these bone material compositional differences are evident
close to the cement line (a major bone interface), they may contribute to the
inferior bone toughness and coupled with the lower lumbar spine bone mineral
density values result in the fragility fractures prevalent in these patients. (c)
2016 American Society for Bone and Mineral Research.
PMID- 27490953
TI - Protocols for Molecular Modeling with Rosetta3 and RosettaScripts.
AB - Previously, we published an article providing an overview of the Rosetta suite of
biomacromolecular modeling software and a series of step-by-step tutorials
[Kaufmann, K. W., et al. (2010) Biochemistry 49, 2987-2998]. The overwhelming
positive response to this publication we received motivates us to here share the
next iteration of these tutorials that feature de novo folding, comparative
modeling, loop construction, protein docking, small molecule docking, and protein
design. This updated and expanded set of tutorials is needed, as since 2010
Rosetta has been fully redesigned into an object-oriented protein modeling
program Rosetta3. Notable improvements include a substantially improved energy
function, an XML-like language termed "RosettaScripts" for flexibly specifying
modeling task, new analysis tools, the addition of the TopologyBroker to control
conformational sampling, and support for multiple templates in comparative
modeling. Rosetta's ability to model systems with symmetric proteins, membrane
proteins, noncanonical amino acids, and RNA has also been greatly expanded and
improved.
PMID- 27490958
TI - The Predentary Bone and Its Significance in the Evolution of Feeding Mechanisms
in Ornithischian Dinosaurs.
AB - The characteristic predentary bone in ornithischian dinosaurs is a unique,
unpaired element located at the midline of the mandibular symphysis. Although
traditionally thought to only be a plant "nipping" bone, the true functional
significance of this bone among feeding mechanisms of ornithischian dinosaurs is
poorly known. Recent studies of a select few ornithischian genera have suggested
rotation of the mandibular corpora around their long axes relative to their
midline joint articulation with the predentary bone. This study aims to re
evaluate these hypotheses as well as provide in-depth qualitative comparative
descriptions of predentary bone morphology in ornithischian genera throughout all
subclades, including heterodontosaurids, thyreophorans, ornithopods, and
marginocephalians. Descriptions evaluate overall shape of the predentary, its
articular surfaces contacting the rostral ends of the dentaries, and the
morphology of the rostral extent of the dentaries and their midline symphysis.
Functionally relevant morphologies in each predentary morphotype are accentuated
for further speculation of feeding mechanisms. Three predentary morphotypes are
described throughout ornithischian subclades and each plays a unique role in
feeding adaptations. Most notably, the predentary likely evolved as a midline
axial point of the mandibular symphysis for simultaneous variable movement or
rotation of the mandibular corpora in many, but not all, taxa. This simultaneous
movement of the hemimandibles would have aided in feeding on both sides of the
jaw at once. The function of the predentary as well as other jaw adaptations is
discussed for genera throughout all subclades, focusing on both general shape and
joint morphology. Anat Rec, 299:1358-1388, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27490959
TI - Uptake, distribution in different tissues, and genotoxicity of imidacloprid in
the freshwater fish Australoheros facetus.
AB - The neonicotinoid imidacloprid is under re-evaluation by regulatory agencies
because of the poor current information available regarding its potential
effects. One of the goals of the present study was to determine imidacloprid
uptake and distribution in the freshwater fish Australoheros facetus
experimentally exposed for 24 h and 48 h to 100 MUg/L, 300 MUg/L, and 2500 MUg/L.
The toxicity of imidacloprid to fish reported in the literature is in the
milligrams per liter or gram per liter range, but sublethal effects at micrograms
per liter in some groups other than fish have been described. Another goal of the
present study was to evaluate imidacloprid's potential genotoxicity and to
compare it between the individual compound and a commercial formulation.
Concentrations of imidacloprid were measured in water, brain, muscle, gills, gut,
liver, and blood by liquid chromatography-tandem mass spectrometry. Imidacloprid
was detected in all the tissues tested. Concentrations were higher after 48 h
than after 24 h in liver, gills, gut, and muscle, whereas in brain and blood they
were similar at both exposure times. Although there was no accumulation, only
uptake, of imidacloprid, genotoxicity was observed. In fish exposed to IMIDA NOVA
35(r) , increased micronucleus frequency at 100 ug/L and 1000 ug/L was detected,
whereas in the imidacloprid active ingredient bioassay it increased only at 1000
ug/L imidacloprid. The present findings warn of the possible consequences that
fish living in freshwater ecosystems can suffer. Environ Toxicol Chem 2017;36:699
708. (c) 2016 SETAC.
PMID- 27490960
TI - One-Pot Synthesis of 2-Cyano-1,4-diketones: Applications to Synthesis of
Cyanosubstituted Furans, Pyrroles, and Dihydropyridazines.
AB - A convenient synthetic route for the construction of functionalized 2-cyano-1,4
diketones has been established from the nucleophilic substitution of 2
bromoacetophenones with NaCN via the in situ-generated beta-ketonitriles. This
method was further applied to the synthesis of cyanosubstituted furans, pyrroles,
or dihydropyridazines, which were obtained in good to excellent yields using
Bi(OTf)3, NH4OAc, or N2H4. The key structures were confirmed by X-ray single
crystal diffraction analysis.
PMID- 27490961
TI - New Perspectives in Multiple Primary Colorectal Cancer: A Surgical Approach.
AB - BACKGROUND: We identify the features of multiple primary colorectal cancer
(MPCC), synchronous colorectal cancer (SCRC) and metachronous colorectal cancer
(MCRC), and distinguish between the cases that require a more extensive surgery
and those where the parameters of SCRC might be important to prevent the
development of MCRC. METHODS: We gathered up consecutive individuals with MPCC,
50 for each category, and 100 consecutive individuals diagnosed with 'single'
colorectal cancer. Clinical and familiar information was obtained. We classified
both SCRC and MCRC according to locations. RESULTS: MPCC were associated with
polyps, both in earlier stages and as sporadic forms. SCRC located in the right
colon were most frequently of the mucinous type. MCRC developed SCRC in 24%,
along the entire colon, with familiar cancer antecedents. SCRC patients
undergoing a total colectomy were younger, with the cancer spread throughout the
entire colon and a larger number of polyps, whereas MCRC were predominantly
adenomatous polyps. We found 2 risk factors for SCRC that led to the development
of MCRC: rectal location and higher number of polyps. CONCLUSIONS: SCRC possibly
involves more than an environmental component. MCRC appears to be the producer of
polyps that evolve into cancer at different times, emphasising the idea of a
genetic predisposition. Studies are required to find biomarkers that define
patients with higher risk of developing MCRC within SCRC.
PMID- 27490962
TI - Glasgow Gloom or Leeds Glue? Dialect-Specific Vowel Duration Constrains Lexical
Segmentation and Access.
AB - Timing cues are important in many aspects of speech processing, fromidentifying
segments to locating word and phrase boundaries. They vary across accents, yet
representation and processing of this variation are poorly understood. We
investigated whether an accent difference in vowel duration affects lexical
segmentation and access. In Glasgow English (GE), /i u e o/ are shorter than in
Leeds English (LE), especially for /i u/ before voiced stops and nasals. In a
word-spotting experiment, GE and LE participants heard nonsense sequences (e.g.
pobegloomezh) containing embedded words (gloom, glue), with segmental qualities
intermediate between GE and LE. Critical vowel durations were manipulated
according to accent (GE-appropriate vowels shorter than LE-appropriate ones) and
phonological context (vowels shortest before voiceless stops < voiced
stops/nasals < voiced fricatives). GE participants generally spotted words like
gloom more accurately with GE-appropriate than LE-appropriate vowels. LE
participants were less accurate than GE participants to spot words like gloom
with GE-appropriate vowels, but more likely to spot embeddings like glue. These
results were broadly as predicted based on the accent differences, but depended
less than expected on the accent-specific phonological constraints. We discuss
theoretical implications regarding the representation of duration and the time
course of lexical access.
PMID- 27490963
TI - Comprehension of texts by deaf elementary school students: The role of
grammatical understanding.
AB - BACKGROUND: The aim of this study was to analyze how the reading process of deaf
Spanish elementary school students is affected both by those components that
explain reading comprehension according to the Simple View of Reading model:
decoding and linguistic comprehension (both lexical and grammatical) and by other
variables that are external to the reading process: the type of assistive
technology used, the age at which it is implanted or fitted, the participant's
socioeconomic status and school stage. DESIGN: Forty-seven students aged between
6 and 13 years participated in the study; all presented with profound or severe
prelingual bilateral deafness, and all used digital hearing aids or cochlear
implants. Students' text comprehension skills, decoding skills and oral
comprehension skills (both lexical and grammatical) were evaluated. RESULTS:
Logistic regression analysis indicated that neither the type of assistive
technology, age at time of fitting or activation, socioeconomic status, nor
school stage could predict the presence or absence of difficulties in text
comprehension. Furthermore, logistic regression analysis indicated that neither
decoding skills, nor lexical age could predict competency in text comprehension;
however, grammatical age could explain 41% of the variance. Probing deeper into
the effect of grammatical understanding, logistic regression analysis indicated
that a participant's understanding of reversible passive object-verb-subject
sentences and reversible predicative subject-verb-object sentences accounted for
38% of the variance in text comprehension. CONCLUSIONS: Based on these results,
we suggest that it might be beneficial to devise and evaluate interventions that
focus specifically on grammatical comprehension.
PMID- 27490964
TI - Astigmatism corrected common path probe for optical coherence tomography.
AB - BACKGROUND AND OBJECTIVES: Optical coherence tomography (OCT) catheters for
intraluminal imaging are subject to various artifacts due to reference-sample arm
dispersion imbalances and sample arm beam astigmatism. The goal of this work was
to develop a probe that minimizes such artifacts. MATERIALS AND METHODS: Our
probe was fabricated using a single mode fiber at the tip of which a glass spacer
and graded index objective lens were spliced to achieve the desired focal
distance. The signal was reflected using a curved reflector to correct for
astigmatism caused by the thin, protective, transparent sheath that surrounds the
optics. The probe design was optimized using Zemax, a commercially available
optical design software. Common path interferometric operation was achieved using
Fresnel reflection from the tip of the focusing graded index objective lens. The
performance of the probe was tested using a custom designed spectrometer-based
OCT system. RESULTS: The probe achieved an axial resolution of 15.6 MUm in air, a
lateral resolution 33 MUm, and a sensitivity of 103 dB. A scattering tissue
phantom was imaged to test the performance of the probe for astigmatism
correction. Images of the phantom confirmed that this common-path, astigmatism
corrected OCT imaging probe had minimal artifacts in the axial, and lateral
dimensions. CONCLUSIONS: In this work, we developed an astigmatism-corrected,
common path probe that minimizes artifacts associated with standard OCT probes.
This design may be useful for OCT applications that require high axial and
lateral resolutions. Lasers Surg. Med. 49:312-318, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27490965
TI - The effects of short-term JNK inhibition on the survival and growth of aged
sympathetic neurons.
AB - During the course of normal aging, certain populations of nerve growth factor
(NGF)-responsive neurons become selectively vulnerable to cell death. Studies
using dissociated neurons isolated from neonates have shown that c-Jun N-terminal
kinases (JNKs) are important in regulating the survival and neurite outgrowth of
NGF-responsive sympathetic neurons. Unlike neonatal neurons, adult sympathetic
neurons are not dependent on NGF for their survival. Moreover, the NGF precursor,
proNGF, is neurotoxic for aging but not young adult NGF-responsive neurons.
Because of these age-related differences, the effects of JNK inhibition on the
survival and growth of sympathetic neurons isolated from aged mice were studied.
Aged neurons, as well as glia, were found to be dependent on JNK for their growth
but not their survival. Conversely, proNGF neurotoxicity was JNK-dependent and
mediated by the p75-interacting protein NRAGE, whereas neurite outgrowth was
independent of NRAGE. These results have implications for the potential use of
JNK inhibitors as therapies for ameliorating age-related neurodegenerative
disease.
PMID- 27490966
TI - Cheminformatics Based Machine Learning Models for AMA1-RON2 Abrogators for
Inhibiting Plasmodium falciparum Erythrocyte Invasion.
AB - Malaria remains a dreadful disease by putting every year about 3.4 billion people
at risk and resulting into mortality of 627 thousand people worldwide. Existing
therapies based upon Quinines and Artemisinin-based combination therapies have
started showing resistance, pressing the need for search of anti-malarials with
different mechanisms of action. In this respect erythrocyte invasion by
Plasmodium is immensely crucial, as being obligate intracellular parasite it must
invade host cells. This process is mediated by interaction between conserved
Apical Membrane Antigen (AMA1) and Rhoptry Neck (RON2) protein, which is
compulsory for successful invasion of erythrocyte by Plasmodium and manifestation
of the disease Malaria. Here, using the physicochemical properties of the
compounds available from a confirmatory high throughput screening, which were
tested for their disruption capability of this crucial molecular interaction, we
trained supervised classifiers and validated their robustness by various
statistical parameters. Best model was used for screening new compounds from
Traditional Chinese Medicine Database. Some of the best hits already find their
use as anti-malarials and the model predicts that an essential part of their
effectiveness is likely due to inhibition of AMA1-RON2 interaction.
Pharmacophoric features have also been identified to ease further designing of
possible leads in an effective way.
PMID- 27490967
TI - Structural Models for the Design of PKMzeta Inhibitors with Neurobiological
Indications.
AB - An atypical protein kinase C, PKMzeta has become an attractive target for various
neurological disorders including long term potentiation, cognition, neuropathic
pain and cancer. Drug discovery efforts have been hindered due to the non
availability of the protein structure and hence in the present study we attempted
to build the open and closed models of the protein PKMzeta using homology
modeling. The models were then used to identify PKMzeta inhibitors utilizing a
high-throughput virtual screening protocol from a large commercial chemical
database. Compounds were selected based on the binding interactions and Glide
score. Compounds were then subjected to in vitro luminescent based kinase assay
for their inhibitory activity on targeted protein. Seven compounds exhibited IC50
s less than or equal to 10 uM. Cell based assays revealed that Lead C3 and Lead
C6 exhibited selectivity towards methylmercury treated neuroblastoma growth
inhibition and suppressed reactive oxygen species with IC50 s of 0.89 and 0.17
uM, respectively. Furthermore, Lead C3 exhibited attenuation of proinflammatory
response with least energy in dynamic simulation studies and thus emerged as a
prototypical lead for further development as novel inhibitor of PKMzeta for
neurological implications.
PMID- 27490968
TI - Quantitative Regression Models for the Prediction of Chemical Properties by an
Efficient Workflow.
AB - Rapid safety assessment is more and more needed for the increasing chemicals both
in chemical industries and regulators around the world. The traditional
experimental methods couldn't meet the current demand any more. With the
development of the information technology and the growth of experimental data, in
silico modeling has become a practical and rapid alternative for the assessment
of chemical properties, especially for the toxicity prediction of organic
chemicals. In this study, a quantitative regression workflow was built by KNIME
to predict chemical properties. With this regression workflow, quantitative
values of chemical properties can be obtained, which is different from the binary
classification model or multi-classification models that can only give
qualitative results. To illustrate the usage of the workflow, two predictive
models were constructed based on datasets of Tetrahymena pyriformis toxicity and
Aqueous solubility. The qcv (2) and qtest (2) of 5-fold cross validation and
external validation for both types of models were greater than 0.7, which implies
that our models are robust and reliable, and the workflow is very convenient and
efficient in prediction of various chemical properties.
PMID- 27490969
TI - Identification of Lead Compounds as Inhibitors of STAT3: Design, Synthesis and
Bioactivity.
AB - STAT3 belongs to the signal transducers and activators of transcription (STAT)
family. It has been demonstrated that STAT3 is constitutively activated in many
tumors, playing a role in carcinogenesis and tumor progression. For this reason,
it has being considered a potential target for cancer therapy. In this context,
we have designed, synthesized and evaluated 1,4-dimethyl-carbazole derivatives,
targeting the STAT3 protein. Moreover, MTT assay performed on A375 and HeLa,
showed significant antiproliferative activity of some of synthesized compounds (3
5). The same compounds (3-5) considerably reduced STAT3 expression, as
demonstrated by Western blot analysis. Our multidisciplinary approach shows that
1,4-dimethyl-carbazoles are potential building blocks to develop more affinity
ligands of STAT3.
PMID- 27490970
TI - Pred-hERG: A Novel web-Accessible Computational Tool for Predicting Cardiac
Toxicity.
AB - The blockage of the hERG K(+) channels is closely associated with lethal cardiac
arrhythmia. The notorious ligand promiscuity of this channel earmarked hERG as
one of the most important antitargets to be considered in early stages of drug
development process. Herein we report on the development of an innovative and
freely accessible web server for early identification of putative hERG blockers
and non-blockers in chemical libraries. We have collected the largest publicly
available curated hERG dataset of 5,984 compounds. We succeed in developing
robust and externally predictive binary (CCR~0.8) and multiclass models
(accuracy~0.7). These models are available as a web-service freely available for
public at http://labmol.farmacia.ufg.br/predherg/. Three following outcomes are
available for the users: prediction by binary model, prediction by multi-class
model, and the probability maps of atomic contribution. The Pred-hERG will be
continuously updated and upgraded as new information became available.
PMID- 27490971
TI - Coupled Biosynthesis of Volatiles and Salinosporamide A in Salinispora tropica.
AB - Terrestrial bacteria, especially actinomycetes, are known to be prolific
producers of volatile compounds. We show here that bacteria from ocean sediments
can also release complex bouquets of volatiles. The actinomycete Salinispora
tropica produces cyclohexenyl compounds not previously known in nature, such as
methyl cyclohex-2-ene-1-carboxylate (9), methyl 2-(cyclohex-2-en-1-yl)acetate
(10), methyl (E/Z)-2-(cyclohex-2-en-1-ylidene)acetate (11/12), and related
alcohols 8 and 13. These compounds were identified by GC/MS and confirmed by
synthesis. In addition, rare spiroacetals, aromatic compounds, short-chain acids
and esters, alcohols, and various cyclic compounds were produced by the bacteria.
The biosynthesis of the cyclohexenyl compounds is closely coupled to that of
cyclohexenylalanine (4), a building block of salinosporamide A, a proteasome
inhibitor produced by S. tropica. Analysis of S. tropica strains that harbor
knockouts of the salinosporamide biosynthetic genes salX and salD, coupled with
feeding experiments, revealed that 3-(cyclohex-2-en-1-yl)-2-oxopropanoic acid
(60) and 3-(cyclohex-2-en-1-ylidene)-2-oxopropanoic acid (isomers 61 and 62) are
important intermediates in the biosynthesis of salinosporamide A, 4, and 8-13.
PMID- 27490972
TI - Effects of a stocking on plantar sensation in individuals with and without ankle
instability.
AB - INTRODUCTION: It is unknown whether footwear has a beneficial or deleterious
effect on cutaneous sensitivity. We aimed to test a preliminary model of footwear
and its effect on tactile perception among groups of controls, copers, and
chronic ankle instability participants. METHODS: Light-touch thresholds were
obtained for 45 participants (age: 20.2 +/- 2.8 years; height: 167.6 +/- 9.8 cm;
mass: 66.3 +/- 14.7 kg) using Semmes-Weinstein monofilaments at the head of the
first metatarsal (1MT), base of the fifth metatarsal (5MT), and calcaneus (CAL).
Baseline measurements were compared with those taken after wearing a nylon
stocking for 5 min. RESULTS: Thresholds were increased at all 3 sites when the
stocking was worn (P < 0.05). Controls had an increase at 1MT, copers had an
increase at 5MT and CAL, and chronic ankle instability had an increase at CAL.
CONCLUSIONS: Cutaneous thresholds increase when subjects wear a nylon stocking, a
model for the sensory effects of footwear. A history of ankle injury appears to
influence which sites have altered sensibility. Muscle Nerve, 2016. Muscle Nerve
55: 513-519, 2017.
PMID- 27490973
TI - Anti-ApoA-1 IgG serum levels predict worse poststroke outcomes.
AB - BACKGROUND: Autoantibodies to apolipoprotein A-1 (anti-ApoA-1 IgG) were shown to
predict major adverse cardiovascular events and promote atherogenesis. However,
their potential relationship with clinical disability and ischaemic lesion volume
after acute ischaemic stroke (AIS) remains unexplored. MATERIALS AND METHODS: We
included n = 76 patients admitted for AIS and we investigated whether baseline
serum anti-ApoA-1 IgG levels could predict (i) AIS-induced clinical disability
[assessed by the modified Rankin Scale (mRS)], and (ii) AIS-related ischaemic
lesion volume [assessed by Computed Tomography (CT)]. We also evaluated the
possible pro-apoptotic and pro-necrotic effects of anti-ApoA-1 IgG on human
astrocytoma cell line (U251) using flow cytometry. RESULTS: High levels of anti
ApoA-1 IgG were retrieved in 15.8% (12/76) of patients. Increased baseline levels
of anti-ApoA-1 IgG were independently correlated with worse mRS [beta = 0.364; P
= 0.002; adjusted odds ratio (OR): 1.05 (95% CI 1.01-1.09); P = 0.017] and CT
assessed ischaemic lesion volume [beta = 0.333; P < 0.001; adjusted OR: 1.06 (95%
CI 1.01-1.12); P = 0.048] at 3 months. No difference in baseline clinical,
biochemical and radiological characteristics was observed between patients with
high vs. low levels of anti-ApoA-1 IgG. Incubating human astrocytoma cells with
anti-ApoA-1 IgG dose dependently induced necrosis and apoptosis of U251 cells in
vitro. CONCLUSION: Anti-ApoA-1 IgG serum levels at AIS onset are associated with
poorer clinical recovery and worse brain lesion volume 3 months after AIS. These
observations could be partly explained by the deleterious effect of anti-ApoA-1
IgG on human brain cell survival in vitro and may have clinical implication in
the prediction of poor outcome in AIS.
PMID- 27490974
TI - Electrical Conductivity, Thermoelectric Power, and Equilibration Kinetics of Nb
Doped TiO2.
AB - This work considers the equilibration kinetics of Nb-doped TiO2 single crystal
(0.066 atom % Nb) during oxidation and reduction within a wide range of
temperature (1073-1298 K) and oxygen activity (10(-14)-10(5) Pa). The associated
semiconducting properties were determined using simultaneous measurements of both
electrical conductivity and thermoelectric power. It is shown that the chemical
diffusion coefficient in the strongly reducing regime, p(O2) < 10(-5) Pa, is 4
orders of magnitude larger than that in the reducing and oxidizing regimes, 10 Pa
< p(O2) < 22 kPa. The derived theoretical model considers the gas/solid kinetics
for the TiO2/O2 system in terms of two diffusion regimes: the fast regime related
to fast defects (oxygen vacancies and titanium interstitials) and leading to
quasi-equilibrium, and the slow regime associated with slow defects (titanium
vacancies) resulting in the gas/solid equilibrium. It has been shown that
incorporation of donor-type elements, such as niobium, and imposition of oxygen
activity above a certain critical value, results in a substantial reduction in
the concentration of high mobility defects and leads to slowing down the
equilibration kinetics. In consequence, the fast kinetic regime is not observed.
Comparison of the kinetic data for Nb-doped TiO2 single crystal (this work) and
polycrystalline Nb-doped TiO2 (reported before) indicates that the gas/solid
kinetics for the polycrystalline specimen at higher oxygen activities is rate
controlled by the transport of oxygen within individual grains.
PMID- 27490975
TI - Reply.
PMID- 27490976
TI - PEMBROLIZUMAB ADMINISTRATION ASSOCIATED WITH POSTERIOR UVEITIS.
AB - PURPOSE: To describe the development of uveitis and retinal vasculitis in
association with pembrolizumab treatment for metastatic uveal melanoma. METHODS:
A case report and a brief review of the literature are presented. Information
collected and reported include the patient's clinical course, physical
examination findings, fluorescein angiogram images, retinal photographs, and her
response to treatment. RESULTS: A 54-year-old woman was diagnosed with a large
choroidal malignant melanoma and had the affected eye enucleated. Pathology
confirmed a mixed cell choroidal melanoma, and gene expression profiling was
Class 2. Seventeen months after enucleation, the patient was diagnosed with
metastatic uveal melanoma to the liver. Disease progression was observed during
ipilimumab treatment. Pembrolizumab treatment was initiated, and after four
infusions, she presented to clinic complaining of floaters and blurred vision.
Examination revealed a nongranulomatous panuveitis characterized by perivascular
retinal pigment epithelium pigmentary changes, retinal venous sheathing, 1+
anterior chamber and vitreous cellular reaction, 2+ vitreous haze, and optic disk
edema. A dexamethasone sustained-release implant was administered and the uveitis
regressed. A relapse in symptoms occurred but quickly subsided with a repeat
injection. CONCLUSION: Pembrolizumab may induce a uveitic reaction. There is
mounting evidence that patients using prembrolizumab should be educated and
monitored for signs of uveitis.
PMID- 27490977
TI - BRANCH RETINAL ARTERY OCCLUSION ASSOCIATED WITH PARACENTRAL ACUTE MIDDLE
MACULOPATHY IN A PATIENT WITH LIVEDO RETICULARIS.
AB - PURPOSE: To report the occurrence of a branch retinal artery occlusion with
paracentral acute middle maculopathy in an otherwise healthy young man with a
history of livedo reticularis (LR). METHODS: Retrospective case report. PATIENTS:
A 21-year-old man with a history of LR being treated with pentoxifylline
developed an acute branch retinal artery occlusion with initial best-corrected
visual acuity at presentation of 20/80. RESULTS: A thorough diagnostic work up
was negative for potential causes of branch retinal artery occlusion or LR. The
patient was continued on pentoxifylline and started on aspirin 81 mg daily. At
five-month follow-up, vision had improved to 20/25. Optical coherence tomography
testing showed a hyperreflective band in the inner nuclear layer and outer
plexiform layers in the affected eye that ultimately thinned, consistent with
paracentral acute middle maculopathy. CONCLUSION: To our knowledge, this is the
first case of branch retinal artery occlusion occurring in a patient with a
history of LR. This could potentially be an early manifestation of Sneddon
syndrome, a rare entity characterized by LR and cerebrovascular disease, which
has been previously associated with central retinal artery occlusions.
PMID- 27490978
TI - Correspondence.
PMID- 27490979
TI - Chemodiversity of the Essential Oil from Leaves of Abies nebrodensis (Lojac.)
Mattei.
AB - Abies nebrodensis (Lojac.) Mattei (Pinaceae) is a species occurring in a very
small population only in a restricted area of Sicily. Its taxonomic
classification as different species has been object of discussion. In this work
the chemical composition of the essential oil from the leaves is presented for
the first time and compared to the essential oils from other euroasiatic species
reported in literature. Peculiar characteristics of the essential oil of A.
nebrodensis are highlighted.
PMID- 27490980
TI - Multi-disciplinary management of complex pressure sore reconstruction: 5-year
review of experience in a spinal injuries centre.
AB - INTRODUCTION In our regional spinal injuries unit, complex pressure ulcer
reconstruction is facilitated by a monthly multidisciplinary team clinic. This
study reviews a series of the more complex of these patients who underwent
surgery as a joint case between plastics and other surgical specialties, aiming
to provide descriptive data as well as share the experience of treating these
complex wounds. MATERIALS AND METHODS Patients operated on as a joint case from
2010 to 2014 were identified through a locally held database and hospital records
were then retrospectively reviewed for perioperative variables. Descriptive
statistics were collected. RESULTS 12 patients underwent 15 procedures as a joint
collaboration between plastic surgery and other surgical specialties: one with
spinal surgery, 12 with orthopaedic and two with both orthopaedic and urology
involvement. Ischial and trochanteric wounds accounted for 88% of cases with five
Girdlestone procedures being performed and 12 requiring soft-tissue flap
reconstruction. Mean operative time was 3.8hours. Four patients required high
dependency care and 13 patients received long-term antibiotics. Only three minor
complications (20%) were seen with postoperative wound dehiscence. DISCUSSION The
multidisciplinary team clinic allows careful assessment and selection of patients
appropriate for surgical reconstruction and to help match expectations and
limitations imposed by surgery, which are likely to influence their current
lifestyle in this largely independent patient group. Collaboration with other
specialties gives the best surgical outcome both for the present episode as well
as leaving avenues open for potential future reconstruction.
PMID- 27490981
TI - The use of FloSeal haemostatic sealant in the management of epistaxis: a
prospective clinical study and literature review.
AB - INTRODUCTION It is standard practice in the UK that if conservative measures or
chemical cautery fail to control epistaxis, patients receive nasal packing which
is often uncomfortable, requires admission and has well documented associated
morbidity. Our study aims to evaluate the use of FloSeal haemostatic sealant in
managing patients with epistaxis. MATERIALS AND METHODS Patients were identified
from those referred with active epistaxis. A successful outcome was defined as
complete haemostasis with FloSeal alone, with no further significant bleeding
requiring admission or further interventions in the subsequent 7 days. Patients
reported satisfaction using a ten-point visual analogue scale. Ear, nose and
throat doctors recorded patient demographics, time to prepare FloSeal, length of
stay, need for further treatment and adverse events on an electronic database.
RESULTS 30 patients were enrolled in the study. The mean time to prepare FloSeal
was 5 minutes. The success rate of FloSeal was 90%. The mean length of stay was
2.75 hours. The mean patient satisfaction with FloSeal was 8.4/10. No adverse
events occurred. DISCUSSION FloSeal was found to be effective in controlling
anterior epistaxis. There was a single case of posterior epistaxis which required
operative management. The literature largely supports FloSeal in anterior
epistaxis, but indicates sphenopalatine artery ligation as the definitive
management of posterior epistaxis. CONCLUSIONS Our data support the use of
FloSeal in patients with anterior epistaxis not controlled with conservative
measures or chemical cautery. It was found to be easy to use, is well tolerated
by patients and is efficient in financial terms.
PMID- 27490983
TI - A folded up treatment sheet is preferable to a sandbag.
PMID- 27490982
TI - Correlation of Ki-67 indices from biopsy and resection specimens of
neuroendocrine tumours.
AB - INTRODUCTION Neuroendocrine tumours (NETs) are a heterogeneous group of tumours
with a highly variable presentation and prognosis. Management decisions are
complex. Ki-67 levels in tissue samples are a key indicator used to grade tumours
and guide treatment. This study assessed whether the Ki-67 index and tumour grade
generated from tissue samples correlated with that assessed in resection
specimens. METHODS This was a retrospective cohort analysis of all patients who
had both a tissue sample and a resection specimen analysed in our trust, a
tertiary referral centre, during 2012 and 2013. RESULTS Data from 36 patients
were reviewed. Ki-67 indices from tissue samples and resection specimens showed
strong correlation (r=0.95, p<0.001). Tumour grading was the same in the tissue
sample and resection specimens for 22 patients (61.1%). In four patients (11.1%),
the tissue sample overestimated the grade while in ten (27.8%), the sample
underestimated the grade. CONCLUSIONS In most cases, the Ki-67 index and tumour
grade from the tissue sample matched that of the resection specimen. However, in
nearly 40% of cases, the tissue sample grading did not match the resection tumour
grading. In the majority of these, the tissue sample underestimated disease
activity. A low Ki-67 index in a tissue sample should therefore be taken as
provisional and should not, in isolation, persuade clinicians to choose a more
conservative treatment approach if there is clinical, biochemical or radiological
evidence suggestive of a more aggressive disease pathology.
PMID- 27490984
TI - A case series of a magnetic bone conduction hearing implant.
AB - The objective of the study was to retrospectively review the postoperative
outcomes of patients from a single centre who were implanted with a magnetic bone
conduction hearing implant system. The medical and audiological case notes of all
patients (n = 34) in a tertiary referral centre ENT department who had been
implanted with a Baha(r) 4 Attract System between October 2013 and April 2015
were reviewed retrospectively. The main outcome measures were use of the aid and
complications from implantation or use of the aid. Results indicated that 23
patients had no significant postoperative problems; 5 required an alteration in
magnet strength; 1 reported troublesome tinnitus; 1 had the implant changed to an
abutment system; 1 had the magnet removed; 1 has ongoing skin problems; 2 have
been changed to a newer, lighter sound processor. The majority of patients had
good outcomes from the magnetic bone conduction aid. A proportion of patients had
significant problems requiring medical attention.
PMID- 27490985
TI - Mechanisms, patterns and outcomes of paediatric polytrauma in a UK major trauma
centre.
AB - Introduction Paediatric trauma is a significant burden to healthcare worldwide
and accounts for a large proportion of deaths in the UK. Methods This
retrospective study examined the epidemiological data from a major trauma centre
in the UK between January 2012 and December 2014, reviewing all cases of moderate
to severe trauma in children. Patients were included if aged <=16 years and if
they had an abbreviated injury scale score of >=2 in one or more body region.
Results A total of 213 patients were included in the study, with a mean age of
7.8 years (standard deviation [SD]: 5.2 years). The most common cause of injury
was vehicle related incidents (46%). The median length of hospital stay was 5
days (interquartile range [IQR]: 4-10 days). Approximately half (52%) of the
patients had to stay in the intensive care unit, for a median of 1 day (IQR: 0-2
days). The mortality rate was 6.6%. The mean injury severity score was 19 (SD:
10). Pearson's correlation coefficient showed a positive correlation for injury
severity score with length of stay in hospital (p<0.001). Conclusions There is
significant variation in mechanism of injury, severity and pattern of paediatric
trauma across age groups. A multidisciplinary team approach is imperative, and
patients should be managed in specialist centres to optimise their care and
eventual functional recovery. Head injury remained the most common, with
significant mortality in all age groups. Rib fractures and pelvic fractures
should be considered a marker for the severity of injury, and should alert
doctors to look for other associated injuries.
PMID- 27490986
TI - Contemporary characteristics of blunt abdominal trauma in a regional series from
the UK.
AB - INTRODUCTION Blunt abdominal trauma (BAT) is a common injury in recent trauma
series. The characteristics of patients with BAT have changed following the
reconfiguration of UK trauma services. The aim of this study was to build a new
profile for BAT patients undergoing immediate or delayed laparotomy. METHODS All
5,401 consecutive adults presenting with major trauma between April 2012 and
April 2014 in the 3 major trauma centres in the West Midlands were analysed to
identify all patients with BAT. A total of 2,793 patients with a mechanism of
injury or symptomatology consistent with BAT were identified (52%). Outcomes were
analysed using local electronic clinical results systems and notes. RESULTS Of
the 2,793 patients, 179 (6.4%) had a mesenteric or hollow viscus injury, 168
(6.0%) had a hepatobiliary injury, 149 (5.4%) had a splenic injury and 46 (1.6%)
had a vascular injury. Overall, 103 patients (3.7%) underwent an early (<12
hours) laparotomy while 30 (1.1%) underwent a delayed (>12 hours) laparotomy.
Twenty (66.7%) of those undergoing a delayed laparotomy had a hollow viscus
injury. In total, 170 deaths occurred among the BAT patients (6.1%). In the early
laparotomy group, 53 patients died (51.5%) whereas in the delayed laparotomy
group, 6 patients died (20.0%). CONCLUSIONS This series has attempted to provide
the characteristics of patients with BAT in a large contemporary UK cohort. BAT
was found to be a common type of injury. Early and delayed laparotomy occurred in
3.7% and 1.1% of these patients respectively, mostly because of hollow viscus
injury in both cases. Outcomes were comparable with those in the international
literature from regions with mature trauma services.
PMID- 27490987
TI - Mandibular sagittal split osteotomy - A modified technique to reduce
postoperative labiomental paraesthesia.
PMID- 27490988
TI - A giant testicular mixed germ cell tumour.
AB - We present a case that we believe to be the largest mixed germ cell testicular
tumour reported in the United Kingdom. A 23-year-old male was admitted to our
urology department with a large scrotal swelling. The patient was found to have a
giant left testicular tumour and a solitary lung metastasis at presentation. He
underwent an emergency radical orchidectomy and subsequently received four cycles
of bleomycin, etoposide and cisplatin chemotherapy. Four months after starting
treatment, the tumour markers had normalised and a repeat staging computed
tomography showed no active disease. The tumour reached that size because of the
patient's failure to seek medical attention due to fear and embarrassment.
PMID- 27490989
TI - Surgical management of complex intra-articular distal femoral and bicondylar
Hoffa fracture.
AB - Bicondylar Hoffa's fractures of distal femur are rare. We report the case of an
18-year-old male who sustained a closed complex fracture of both femoral condyles
of the left femur on the sagittal plane (Hoffa fracture), combined with distal
metaphyseal fracture. He was treated using parallel plates and interdigitating
screws, with our technique based on an extrapolation of the principles of distal
humerus fixation. The fracture united clinically and radiologically at 16 weeks.
Twelve months postoperatively, the range of movement in the knee was 5 degrees
115 degrees . In this complex case, our technique provided stable fixation of the
fragments and a satisfactory final functional outcome.
PMID- 27490990
TI - AVCpred: an integrated web server for prediction and design of antiviral
compounds.
AB - Viral infections constantly jeopardize the global public health due to lack of
effective antiviral therapeutics. Therefore, there is an imperative need to speed
up the drug discovery process to identify novel and efficient drug candidates. In
this study, we have developed quantitative structure-activity relationship (QSAR)
based models for predicting antiviral compounds (AVCs) against deadly viruses
like human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B
virus (HBV), human herpesvirus (HHV) and 26 others using publicly available
experimental data from the ChEMBL bioactivity database. Support vector machine
(SVM) models achieved a maximum Pearson correlation coefficient of 0.72, 0.74,
0.66, 0.68, and 0.71 in regression mode and a maximum Matthew's correlation
coefficient 0.91, 0.93, 0.70, 0.89, and 0.71, respectively, in classification
mode during 10-fold cross-validation. Furthermore, similar performance was
observed on the independent validation sets. We have integrated these models in
the AVCpred web server, freely available at http://crdd.osdd.net/servers/avcpred.
In addition, the datasets are provided in a searchable format. We hope this web
server will assist researchers in the identification of potential antiviral
agents. It would also save time and cost by prioritizing new drugs against
viruses before their synthesis and experimental testing.
PMID- 27490991
TI - Increasing prevalence of overweight and obesity among children in Vilnius,
Lithuania: comparison of two longitudinal data sets of children born in 1990 and
1996.
AB - SUMMARY: The aim of this study was to assess changes in prevalence of overweight
and obesity among children born in 1996 and 1990 in Vilnius city. The results
were based on comparison of two longitudinal data sets (N = 624 and N = 389)
collected from the personal health records of children born in 1996 and 1990
respectively. No statistically significant differences in final height and BMI
were established between children born in 1990 and 1996; however, both boys and
girls born in 1996 appeared to be higher and heavier at different ages compared
to their peers born in 1990. After controlling for tempo, the differences in
height between the two cohorts have become insignificant for girls, with
exceptions at the age of 3 and 10 years; for boys, the differences between the
cohorts have remained significant, however at a slightly lower level. More
children born in 1996 tended to be overweight and obese. In six years, the
prevalence of overweight in Vilnius children has more than doubled; the
prevalence of obesity has increased up to five times in some age groups.
PMID- 27490993
TI - Treatment of Proximal Interphalangeal Joint Fracture-Dislocations.
PMID- 27490992
TI - Induction immunosuppression for combined heart-lung transplantation.
AB - BACKGROUND: Research on induction immunosuppression in patients undergoing
combined heart-lung transplantation (HLTx) is limited. METHODS: The United
Network for Organ Sharing database was queried from 2000 to 2013 to examine the
influence of induction immunosuppression for combined HLTx in adult (>=18 years)
and adolescent (>=12 and <18 years) recipients. RESULTS: Of 394 eligible combined
HLTx cases (361 adults, 33 adolescents), 384 were included in univariate Cox
analysis and 116 in the multivariate Cox model. Univariate analysis demonstrated
no differences in survival by induction medication and no difference among the
most common maintenance immunosuppression regimens. Adjusting for use of
corticosteroids, multivariate analysis demonstrated no benefit of basiliximab
(HR=3.582; 95% CI: 0.966, 13.279; P=.056), thymoglobulin/antilymphocyte globulin
(ALG)/antithymocyte globulin (ATG) (HR=0.808; 95% CI: 0.134, 4.888; P=.817),
alemtuzumab (HR=0.369; 95% CI: 0.087, 1.563; P=.176), or other induction
medications (HR=1.511; 95% CI: 0.146, 15.610; P=.729), compared to no induction
medication, with respect to mortality hazard post-HLTx. There were also no
differences in treated acute rejection episodes by type of induction
immunosuppression. CONCLUSIONS: Induction immunosuppression with contemporary
agents does not improve survival after combined HLTx.
PMID- 27490994
TI - The Cavovarus Foot in Hereditary Motor and Sensory Neuropathies.
PMID- 27490995
TI - Venous Thromboembolic Disease in Foot and Ankle Surgery.
PMID- 27490996
TI - Neurological and Vascular Complications Associated with Supracondylar Humeral
Fractures in Children.
PMID- 27490997
TI - The Assessment and Treatment of High-Grade Lumbosacral Spondylolisthesis and
Spondyloptosis in Children and Young Adults.
PMID- 27490998
TI - Phase Structure Transition and Properties of Salt-Free Phosphoric Acid/Non-ionic
Surfactants in Water.
AB - Precise control of phase structure transition for the synthesis of multi
dimensional soft materials is a fascinating target in amphiphilic molecule self
assembly. Here, we demonstrate a spontaneous formation of a closely packed
lamellar phase consisting of uni- and multi-lamellar vesicles through the
incorporation of a small amount of an extractant, di(2-ethylhexyl)phosphoric acid
(DEHPA), into the highly swollen, planar lamellar phase of a non-ionic
tetraethylene glycol monododecyl ether (C12EO4) surfactant in water. It is
figured out that the introduction of negative membrane charges results in the
electrostatic repulsion among the lamellae, which suppresses the Helfrich
undulation and induces a phase structure transition from planar lamellae to
closely packed vesicles. Our results provide important insight into amphiphilic
molecule self-assembly, where additives and pH can satisfy the opportunities for
the precise tuning of the lamellar structures, which makes a way for the
development of lamellar soft materials.
PMID- 27490999
TI - Gap junction as an intercellular glue: Emerging roles in cancer EMT and
metastasis.
AB - Metastasis is a common phenomenon in the progression and dissemination of cancer.
It is estimated that metastasis accounts for 90% cancer-related mortality.
Although the formation of tumor metastasis is relatively well understood, the
underlying molecular mechanisms responsible for the emergence of aggressive
cancer phenotype are still elusive. Figuring out the mechanisms by which cancer
cells evade from the tumor is beneficial for obtaining novel and effectively
therapeutic approaches. Primary tumors are composed of various subpopulations of
cells with heterogeneous metastatic characteristics and the occurrence of
metastatic dissemination is mainly dependent upon the interactions between tumor
and the surrounding microenvironment. Tumor microenvironment (TME) such as
extracellular matrix, macrophages, fibroblasts, stem cells and endothelial cells
can orchestrate events critical to tumor evolution toward metastasis. GJ serves
as an important communication between tumor cells and stromal cells. Increased
GJs coupling blocks metastatic potential in some cancer animal models such as
breast cancer and melanoma. Besides, epithelial-to-mesenchymal transition (EMT)
is also a crucial step in the metastatic process and there are signs that GJs
contribute to cell adhesion and migration (the pathological feature of EMT) in
breast cancer. Therefore, we propose that GJ serves as an intercellular glue to
suppress EMT and cancer metastasis.
PMID- 27491000
TI - Corrigendum to 'Ca2+/calmodulin-dependent protein kinase IIgamma, a critical
mediator of the NF-kappaB network, is a novel therapeutic target in non-small
cell lung cancer' [Cancer Lett. 344 (1), 119-128; March 1, 2014].
PMID- 27491001
TI - Pickering emulsions with alpha-cyclodextrin inclusions: Structure and thermal
stability.
AB - This paper explores structural, interfacial and thermal properties of two types
of Pickering emulsions containing alpha-cyclodextrin inclusion complexes: on one
hand, emulsions were obtained between aqueous solutions of alpha-cyclodextrin and
different oils (fatty acids, olive oil, silicone oil) and on the other hand,
emulsions were obtained between these oils, water and micro or nano-platelet
suspensions with inclusion complexes of hydrophobically-modified polysaccharides.
The emulsions exhibit versatile properties according to the molecular
architecture of the oils. Experiments were performed by microcalorimetry, X-ray
diffraction and confocal microscopy. The aptitude of oil molecules to be threaded
in alpha-cyclodextrin cavity is a determining parameter in emulsification and
thermal stability. The heat flow traces and images showed dissolution,
cooperative melting and de-threading of inclusion complexes which take place
progressively, ending at high temperatures, close or above 100 degrees C. Another
important feature observed in the emulsions with micro-platelets is the partial
substitution of the guest molecules occurring at room temperature at the
oil/water interfaces without dissolution, possibly by a diffusion mechanism of
the oil. Accordingly, the dissolution and the cooperative melting temperatures of
the inclusion crystals changed, showing marked differences upon the type of guest
molecules. The enthalpies of dissolution of crystals were measured and compared
with soluble inclusions.
PMID- 27491002
TI - Fabrication and efficient visible light photocatalytic properties of novel zinc
indium sulfide (ZnIn2S4) - graphitic carbon nitride (g-C3N4)/bismuth vanadate
(BiVO4) nanorod-based ternary nanocomposites with enhanced charge separation via
Z-scheme transfer.
AB - Novel ZnIn2S4-g-C3N4/BiVO4 nanorod-based ternary nanocomposite photocatalysts
with enhanced visible light absorption were synthesized and systematically
characterized to confirm the formation of ZnIn2S4 marigold flowers, the layered
structure of the g-C3N4, BiVO4 nanorods, and the formation of binary and ternary
nanocomposites. The visible light absorption of BiVO4 was significantly improved
after coupling with g-C3N4 and ZnIn2S4, which was confirmed by UV-visible diffuse
reflectance spectroscopic analysis. Ternary ZnIn2S4-g-C3N4/BiVO4 nanocomposites
exhibited excellent visible light photocatalytic decomposition efficiency (VL
PDE) when used for the degradation of congo red (CR) dye and metronidazole (MTZ)
pharmaceutical, as well as excellent stability and reusability. The ternary
5%ZnIn2S4-50%-g-C3N4/BiVO4 nanocomposite showed higher VL-PDE for CR (81.5%) and
MTZ (59%) degradation than the binary composites, g-C3N4 and BiVO4. Radical
quenching experiments showed that h(+), OH, and O2(-) were the reactive radicals,
validating that the Z-scheme charge carrier transfer mechanism was responsible
for the enhanced VL-PDE of the ternary ZnIn2S4-g-C3N4/BiVO4 nanocomposites, which
was further confirmed by photoluminescence analysis. Furthermore, kinetic studies
showed that the degradation followed pseudo-first-order kinetics, and that the
ternary photocatalysts could be reused up to three times with good stability. The
enhanced visible light absorption, high surface area, high adsorption capacity, Z
scheme charge carrier transfer, and increased lifetime of photo-produced electron
hole pairs were responsible for the increased visible light photocatalytic
decomposition efficiency.
PMID- 27491003
TI - Neuron-like gold-palladium alloy nanostructures: Rapid synthesis and applications
in electrocatalysis and surface-enhanced Raman scattering.
AB - Neuron-like gold-palladium (AuPd) alloy nanostructures were synthesized by
simultaneous reduction of AuCl4(-) and PdCl4(2-) with ascorbic acid, using N
methylimidazole as the structure-director and stabilizing agent. The synthesis
method was simple and seedless, without any template or polymer. The
architectures strongly depended on the concentration of N-methylimidazole,
reaction temperature and time, and hence the formation mechanism was described in
detail. The as-obtained architectures exhibited superior electrocatalytic
activity for ethanol oxidation and surface-enhanced Raman scattering (SERS)
responses, owing to their unique nanostructures with high density of steps,
edges, and corners on their branches, along with the synergetic functions between
Au and Pd.
PMID- 27491004
TI - Improved sensing response of photo activated ZnO thin film for hydrogen peroxide
detection.
AB - The nanostructured ZnO thin films were deposited using spray pyrolysis technique.
Formation of polycrystalinity with hexagonal wurtzite structure was observed from
the structural study. Highly dense spherical shaped nanoparticles with fine
crystallites were observed from the surface morphological studies. The light
induced hydrogen peroxide vapour sensing was done using chemi-resistive method
and its effect on the sensing response was studied and reported.
PMID- 27491005
TI - Site-Specific Photolabeling of the IgG Fab Fragment Using a Small Protein G
Derived Domain.
AB - Antibodies are widely used reagents for recognition in both clinic and research
laboratories all over the world. For many applications, antibodies are labeled
through conjugation to different reporter molecules or therapeutic agents.
Traditionally, antibodies are covalently conjugated to reporter molecules via
primary amines on lysines or thiols on cysteines. While efficient, such labeling
is variable and nonstoichiometric and may affect an antibody's binding to its
target. Moreover, an emerging field for therapeutics is antibody-drug conjugates,
where a toxin or drug is conjugated to an antibody in order to increase or
incorporate a therapeutic effect. It has been shown that homogeneity and
controlled conjugation are crucial in these therapeutic applications. Here we
present two novel protein domains developed from an IgG-binding domain of
Streptococcal Protein G. These domains show obligate Fab binding and can be used
for site-specific and covalent attachment exclusively to the constant part of the
Fab fragment of an antibody. The two different domains can covalently label IgG
of mouse and human descent. The labeled antibodies were shown to be functional in
both an ELISA and in an NK-cell antibody-dependent cellular cytotoxicity assay.
These engineered protein domains provide novel tools for controlled labeling of
Fab fragments and full-length IgG.
PMID- 27491006
TI - A low frequency persistent reservoir of a genomic island in a pathogen population
ensures island survival and improves pathogen fitness in a susceptible host.
AB - The co-evolution of bacterial plant pathogens and their hosts is a complex and
dynamic process. Host resistance imposes stress on invading pathogens that can
lead to changes in the bacterial genome enabling the pathogen to escape host
resistance. We have observed this phenomenon with the plant pathogen Pseudomonas
syringae pv. phaseolicola where isolates that have lost the genomic island PPHGI
1 carrying the effector gene avrPphB from its chromosome are infective against
previously resistant plant hosts. However, we have never observed island
extinction from the pathogen population within a host suggesting the island is
maintained. Here, we present a mathematical model which predicts different
possible fates for the island in the population; one outcome indicated that PPHGI
1 would be maintained at low frequency in the population long term, if it confers
a fitness benefit. We empirically tested this prediction and determined that
PPHGI-1 frequency in the bacterial population drops to a low but consistently
detectable level during host resistance. Once PPHGI-1-carrying cells encounter a
susceptible host, they rapidly increase in the population in a negative frequency
dependent manner. Importantly, our data show that mobile genetic elements can
persist within the bacterial population and increase in frequency under
favourable conditions.
PMID- 27491008
TI - Protective immune responses of major Vgamma2Vdelta2 T-cell subset in M.
tuberculosis infection.
AB - Recent observation that prenyl pyrophosphates bind the Ig superfamily protein
butyrophilin 3A1 (BTN3A1) suggests that modifying BTN3A1 activates major
gammadelta T-cell subset, Vgamma2Vdelta2 T cells. Studies also show that
microbial phosphoantigen HMBPP is required for expansion, pulmonary response,
effector functions and memory polarization of Vgamma2Vdelta2 T cells during
infections. Broad repertoires of cytokines involve expansion, recall-like
expansion and effector functions of Vgamma2Vdelta2 T cells after Mtb infection or
vaccination. Finally, mechanistic studies in nonhuman primate TB model
demonstrate early expansion and differentiation of Vgamma2Vdelta2 T cells during
Mtb infection can increase immune resistance to TB in macaques, with a potential
mechanism of early/sustained IFN-gamma production and CTL killing.
PMID- 27491007
TI - Tuning the anticancer activity of a novel pro-apoptotic peptide using gold
nanoparticle platforms.
AB - Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells.
However, poor cellular penetration of the peptides is often associated with
limited therapeutic efficacy. In this report, a series of peptide-gold
nanoparticle platforms were developed to evaluate the anticancer activity of a
novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and
shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell
internalization as well as anticancer activity of the peptide conjugates. The
smaller nanospheres showed a higher cytotoxicity, morphological change and
cellular uptake compared to larger nanospheres and nanorods, whereas nanorods
showed more hemolytic activity compared to nanospheres. The findings suggested
that the anticancer and biological effects of the peptides induced by intrinsic
apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P
AuNPs) as a function of their size and shape.
PMID- 27491009
TI - Postoperative Radiotherapy Patterns of Care and Survival Implications for
Medulloblastoma in Young Children.
AB - Importance: Postoperative radiotherapy to the craniospinal axis is standard-of
care for pediatric medulloblastoma but is associated with long-term morbidity,
particularly in young children. With the advent of modern adjuvant chemotherapy
strategies, postoperative radiotherapy deferral has gained acceptance in children
younger than 3 years, although it remains controversial in older children.
Objective: To analyze recent postoperative radiotherapy national treatment
patterns and implications for overall survival in patients with medulloblastoma
ages 3 to 8 years. Design, Setting, and Exposures: Using the National Cancer Data
Base, patients ages 3 to 8 years diagnosed as having histologically confirmed
medulloblastoma in 2004 to 2012, without distant metastases, who underwent
surgery and adjuvant chemotherapy with or without postoperative radiotherapy at
facilities nationwide accredited by the Commission on Cancer were identified.
Patients were designated as having "postoperative radiotherapy upfront" if they
received radiotherapy within 90 days of surgery or "postoperative radiotherapy
deferred" otherwise. Factors associated with postoperative radiotherapy deferral
were identified using multivariable logistic regression. Overall survival (OS)
was compared using Kaplan-Meier analysis with log-rank tests and multivariable
Cox regression. Statistical tests were 2-sided. Main Outcomes and Measures:
Postoperative radiotherapy utilization and overall survival. Results: Among 816
patients, 123 (15.1%) had postoperative radiotherapy deferred, and 693 (84.9%)
had postoperative radiotherapy upfront; 36.8% of 3-year-olds and 4.1% of 8-year
olds had postoperative radiotherapy deferred (P < .001). On multivariable
logistic regression, variables associated with postoperative radiotherapy
deferral were age (odds ratio [OR], 0.57 per year; 95% CI, 0.49-0.67 per year)
and year of diagnosis (OR, 1.18 per year; 95% CI, 1.08-1.29 per year). On
survival analysis, with median follow-up of 4.8 years, OS was improved for those
receiving postoperative radiotherapy upfront vs postoperative radiotherapy
deferred (5-year OS: 82.0% vs 63.4%; P < .001). On multivariable analysis,
variables associated with poorer OS were postoperative radiotherapy deferral
(hazards ratio [HR], 1.95; 95% CI, 1.15-3.31); stage M1-3 disease (HR, 1.86; 95%
CI, 1.10-3.16), and low facility volume (HR, 1.75; 95% CI, 1.04-2.94).
Conclusions and Relevance: Our national database analysis reveals a higher-than
expected and increasing rate of postoperative radiotherapy deferral in children
with medulloblastoma ages 3 to 8 years. The analysis suggests that postoperative
radiotherapy deferral is associated with worse survival in this age group, even
in the modern era of chemotherapy.
PMID- 27491010
TI - Pediatric pseudotumor cerebri.
AB - PURPOSE OF REVIEW: Recent findings in the literature regarding the epidemiology,
diagnosis, and treatment of pediatric pseudotumor cerebri (PTC) are described. In
the past, children with PTC have been treated like adult cases; however, the
literature highlights important differences between children and adults with PTC.
RECENT FINDINGS: Revised diagnostic criteria define an opening cerebrospinal
fluid pressure greater than 28 cm water as elevated in the pediatric population.
Obesity is an important risk factor for primary and secondary PTC in post
pubertal children. Magnetic resonance imaging shows findings suggestive of
elevated intracranial pressure in children with PTC, similar to those of adults
with PTC. Diamox and weight loss are effective treatments for PTC patients with
mild visual field loss. Severe papilledema, decreased vision, and optical
coherence tomography measures at presentation identify patients at increased risk
for subsequent visual loss. SUMMARY: Findings summarized in the recent literature
may change practice patterns in the diagnosis and treatment of pediatric PTC.
Although there are many similarities between the adult and pediatric populations,
the differences should be considered when managing children with PTC.
PMID- 27491011
TI - Evidence-Based Medicine vs Traditional Healers in Africa.
PMID- 27491012
TI - Is Trying to Quit Associated With Tooth Loss and Delayed Yearly Dental Visit
Among Smokers? Results of the 2014 Behavioral Risk Factor Surveillance System.
AB - BACKGROUND: The rate of periodontitis in the US population has been estimated to
be close to 50%. Patients with periodontitis, especially those who smoke, suffer
from a high rate of tooth loss. The purpose of this analysis is to evaluate
predictors of poor oral health and oral health habits among smokers and determine
if trying to quit smoking is associated with better oral health or oral health
habits in smokers in the United States. METHODS: Data from the 2014 Behavioral
Risk Factor Surveillance System (BRFSS) were used in the analysis. After limiting
the dataset to smokers, the designated exposure was respondent's report of trying
to quit smoking (yes/no). Two logistic regression models were developed. One
model identified factors associated with having a most recent dental visit longer
than 1 year before the survey. The second model identified factors associated
with loss of six or more teeth. Both models were controlled for confounding
factors. RESULTS: After controlling for confounding, among smokers in the 2014
BRFSS, trying to quit was associated with significantly lower odds of respondents
having their most recent dental visit longer than a year before the survey (odds
ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90 to 0.97) and was a
significant risk factor for having lost six or more teeth (OR: 1.06; 95% CI: 1.02
to 1.10). CONCLUSIONS: Among smokers in the United States, trying to quit is
associated with compliance with yearly dental visits and higher odds of lost
teeth. Future research should investigate optimal approaches for providing
smoking cessation services in the dental setting.
PMID- 27491013
TI - Vitamin D Receptor Gene Polymorphism and Smoking in the Risk of Chronic
Periodontitis.
AB - BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been
implicated in susceptibility to infections and bone-related diseases. However,
their relationship with periodontal disease remains unclear. This cross-sectional
study investigates whether susceptibility to chronic periodontitis (CP) in a Thai
population is associated with VDR polymorphisms. METHODS: Genomic DNA was
obtained from 1,460 participants, aged 39 to 66 years. Genotyping of VDR
polymorphisms (FokI, BsmI, ApaI, and TaqI) was performed using real-time
polymerase chain reaction. Participants were categorized into three groups: 1)
no/mild; 2) moderate; and 3) severe CP. Multinomial logistic regression was used
to determine degree of association between VDR polymorphisms and periodontal
status adjusted for known confounders. RESULTS: The CC+CT genotypes of FokI
polymorphism were associated with severe CP with an odds ratio (OR) of 1.9 (95%
confidence interval [CI]: 1.3 to 2.8). Compared with genotype-negative (TT) non
smokers, positivity for the risk genotypes (CC+CT) alone and current smoking
alone were associated with severe CP with ORs of 1.8 (95% CI: 1.1 to 3.2) and 2.5
(95% CI: 1.0 to 6.2), respectively. The combination of being genotype positive
and smoking further increased the OR to 9.6 (95% CI: 4.5 to 20.4). This combined
effect was 3.7 times (95% CI: 1.2 to 11.1) greater than expected from the sum of
their individual effects, indicating a synergistic interaction. No significant
association was observed between other polymorphisms and CP. CONCLUSION: FokI
CC+CT genotypes were associated with increased susceptibility to severe CP, which
was aggravated further when combined with smoking.
PMID- 27491014
TI - Associations of emotional arousal, dissociation and symptom severity with operant
conditioning in borderline personality disorder.
AB - Those with borderline personality disorder (BPD) display altered evaluations
regarding reward and punishment compared to others. The processing of rewards is
basal for operant conditioning. However, studies addressing operant conditioning
in BPD patients are rare. In the current study, an operant conditioning task
combining learning acquisition and reversal was used. BPD patients and matched
healthy controls (HCs) were exposed to aversive and neutral stimuli to assess the
influence of emotion on learning. Picture content, dissociation, aversive tension
and symptom severity were rated. Error rates were measured. Results showed no
group interactions between aversive versus neutral scenes. The higher emotional
arousal, dissociation and tension, the worse the acquisition, but not reversal,
scores were for BPD patients. Scores from the Borderline Symptom List were
associated with more errors in the reversal, but not the acquisition phase. The
results are preliminary evidence for impaired acquisition learning due to
increased emotional arousal, dissociation and tension in BPD patients. A failure
to process punishment in the reversal phase was associated with symptom severity
and may be related to neuropsychological dysfunctioning involving the
ventromedial prefrontal cortex. Conclusions are limited due to the correlational
study design and the small sample size.
PMID- 27491015
TI - A case of flying insects visiting an anatomy and embalming laboratory in
Medellin, Colombia.
AB - From July to September of 2012, the fauna of flying insects visiting the anatomy
and embalming laboratory of the Tecnologico de Antioquia, Faculty of Forensic
Sciences, located in the city of Medellin, Colombia, were recorded. The first
checklist in the literature of incidental flying insects occurring in this type
of locale is provided, and a brief discussion is given of their behavioral habits
related to this uncommon case.
PMID- 27491016
TI - Scope or scalpel? A matched study of the treatment of large colorectal polyps.
AB - BACKGROUND: Large colorectal polyps can be treated either endoscopically or by
formal resection. The aim of this study was to clarify the relative advantages
and disadvantages of surgical resection and colonoscopic snaring as means of
treating large colorectal polyps. METHODS: This is a matched cohort study,
comparing cases of surgical resection of benign colorectal polyps with endoscopic
resection. Cases drawn from pathology and endoscopy databases were matched for
the size and site of polyps, and the groups were compared for the end points of
complications, length of hospital stay and completeness of the removal of the
polyp. RESULTS: There were 78 patients in each group, with mean ages of 65.6
years (colonoscopy) and 66.8 years (surgery). A total of 39 of the surgery group
and 47 of the colonoscopy group were men. Mean polyp size was 34.1 mm
(colonoscopy) and 32.1 mm (surgery). There was an exact match for polyp location.
Complications occurred in eight colonoscopy patients (10.3%) and 42 surgery
patients (56.0%) (P < 0.001, chi-square). Length of hospital stay was 0 days for
colonoscopy patients and 7.3 +/- 4.7 days for surgery (P < 0.001). The surgery
group was separated into laparoscopic (n = 35) and open (n = 43) surgery. There
was no difference in complication rates (42.4 versus 53.5%, respectively) but
laparoscopic had shorter length of stay (5.8 days +/- 4.9 SD versus 8.4 days +/-
4.3 SD). Recurrence of surgically resected polyps was zero; at last follow-up 13%
of snared polyps persisted. CONCLUSION: Although resection is a more certain and
absolute way of treating benign polyps, endoscopic polypectomy is preferable.
PMID- 27491017
TI - Disparities in Adult Cigarette Smoking - United States, 2002-2005 and 2010-2013.
AB - Although cigarette smoking has substantially declined since the release of the
1964 Surgeon General's report on smoking and health,* disparities in tobacco use
exist among racial/ethnic populations (1). Moreover, because estimates of U.S.
adult cigarette smoking and tobacco use are usually limited to aggregate racial
or ethnic population categories (i.e., non-Hispanic whites [whites]; non-Hispanic
blacks or African Americans [blacks]; American Indians and Alaska Natives
[American Indians/Alaska Natives]; Asians; Native Hawaiians or Pacific Islanders
[Native Hawaiians/Pacific Islanders]; and Hispanics/Latinos [Hispanics]), these
estimates can mask differences in cigarette smoking prevalence among subgroups of
these populations. To assess the prevalence of and changes in cigarette smoking
among persons aged >=18 years in six racial/ethnic populations and 10 select
subgroups in the United States,(?) CDC analyzed self-reported data collected
during 2002-2005 and 2010-2013 from the National Survey on Drug Use and Health
(NSDUH) (2) and compared differences between the two periods. During 2010-2013,
the overall prevalence of cigarette smoking among the racial/ethnic populations
and subgroups ranged from 38.9% for American Indians/Alaska Natives to 7.6% for
both Chinese and Asian Indians. During 2010-2013, although cigarette smoking
prevalence was relatively low among Asians overall (10.9%) compared with whites
(24.9%), wide within-group differences in smoking prevalence existed among Asian
subgroups, from 7.6% among both Chinese and Asian Indians to 20.0% among Koreans.
Similarly, among Hispanics, the overall prevalence of current cigarette smoking
was 19.9%; however, within Hispanic subgroups, prevalences ranged from 15.6%
among Central/South Americans to 28.5% among Puerto Ricans. The overall
prevalence of cigarette smoking was higher among men than among women during both
2002-2005 (30.0% men versus 23.9% women) and 2010-2013 (26.4% versus 21.1%)
(p<0.05). These findings highlight the importance of disaggregating tobacco use
estimates within broad racial/ethnic population categories to better understand
and address disparities in tobacco use among U.S. adults.
PMID- 27491018
TI - Single Cobalt Atoms with Precise N-Coordination as Superior Oxygen Reduction
Reaction Catalysts.
AB - A new strategy for achieving stable Co single atoms (SAs) on nitrogen-doped
porous carbon with high metal loading over 4 wt % is reported. The strategy is
based on a pyrolysis process of predesigned bimetallic Zn/Co metal-organic
frameworks, during which Co can be reduced by carbonization of the organic linker
and Zn is selectively evaporated away at high temperatures above 800 degrees C.
The spherical aberration correction electron microscopy and extended X-ray
absorption fine structure measurements both confirm the atomic dispersion of Co
atoms stabilized by as-generated N-doped porous carbon. Surprisingly, the
obtained Co-Nx single sites exhibit superior ORR performance with a half-wave
potential (0.881 V) that is more positive than commercial Pt/C (0.811 V) and most
reported non-precious metal catalysts. Durability tests revealed that the Co
single atoms exhibit outstanding chemical stability during electrocatalysis and
thermal stability that resists sintering at 900 degrees C. Our findings open up
a new routine for general and practical synthesis of a variety of materials
bearing single atoms, which could facilitate new discoveries at the atomic scale
in condensed materials.
PMID- 27491019
TI - Fragment Coupling with Tertiary Radicals Generated by Visible-Light
Photocatalysis.
AB - Convergent synthesis strategies in which a target molecule is prepared by a
branched approach wherein two or more complex fragments are combined at a late
stage are almost always preferred over a linear approach in which the overall
yield of the target molecule is eroded by the efficiency of each successive step
in the sequence. As a result, bimolecular reactions that are able to combine
complex fragments in good yield and, where important, with high stereocontrol are
essential for implementing convergent synthetic strategies. Although
intramolecular reactions of carbon radicals have long been exploited to assemble
polycyclic ring systems, bimolecular coupling reactions of structurally complex
carbon radicals have rarely been employed to combine elaborate fragments in the
synthesis of structurally intricate molecules. We highlight in this Account
recent discoveries from our laboratories that demonstrate that bimolecular
reactions of structurally elaborate tertiary carbon radicals and electron
deficient alkenes can unite complex fragments in high yield using nearly
equimolar amounts of the two coupling partners. Our discussion begins by
considering several aspects of the bimolecular addition of tertiary carbon
radicals to electron-deficient alkenes that commend these transformations for the
union of structurally complex, sterically bulky fragments. We then discuss how in
the context of synthesizing rearranged spongian diterpenoids we became aware of
the exceptional utility of coupling reactions of alkenes and tertiary carbon
radicals to unite structurally complex synthetic intermediates. Our initial
investigations exploit the early report of Okada that N-(acyloxy)phthalimides
reductively fragment at room temperature in the presence of visible light and
catalytic amounts of the photocatalyst Ru(bpy)3Cl2 to form carbon radicals that
react with alkenes. We show that this reaction of a tertiary radical precursor
and an enone can combine two elaborate enantioenriched fragments in good yield
with the formation of new quaternary and secondary stereocenters. As a result of
the ready availability of tertiary alcohols, we describe two methods that were
developed, one in collaboration with the MacMillan group, to generate tertiary
radicals from tertiary alcohols. In the method that will be preferred in most
instances, the tertiary alcohol is esterified in high yield to give a tert-alkyl
hemioxalate salt, which-without purification-reacts with electron-deficient
alkenes in the presence of visible light and an Ir(III) photocatalyst to give
coupled products having a newly formed quaternary carbon in high yield.
Hemioxalate salts containing Li, Na, K, and Cs countercations can be employed in
this reaction, whose only other product is CO2. These reactions are carried out
using nearly equimolar amounts of the addends, making them ideal for coupling of
complex fragments at the late stage in a synthetic sequence. The attractive
attributes of the fragment-coupling chemistry that we discuss in this Account are
illustrated by an enantioselective total synthesis of a tricyclic trans-clerodane
diterpenoid in eight steps and 34% overall yield from commercially available
precursors. We anticipate that bimolecular reactions of carbon radicals will be
increasingly used for fragment coupling in the future.
PMID- 27491020
TI - Changes in grape polyphenols (V. vinifera L.) as a consequence of post-harvest
withering by high-resolution mass spectrometry: Raboso Piave versus Corvina.
AB - Grape dehydration is an oenological process used for the production of high
quality reinforced and sweet wines. Corvina and Raboso Piave are two red grape
varieties used for production of high-quality Italian wines, such as Recioto,
Amarone di Valpolicella and Raboso Passito. Changes of polyphenolic composition
of the grapes as a consequence of the withering were studied by ultra-high
performance liquid chromatography-quadrupole time of flight mass spectrometry
(UHPLC/QTOF); for identification of compounds a homemade HR-MS database of grape
and wine metabolites, was used. Concomitant with trans-resveratrol and
viniferins, relevant increases of other stilbenes (piceatannol, resveratrol
trimers and tetramers) and antioxidant compounds (quercetin, syringetin and
tamarixetin) were observed. These compounds are part of the induced metabolism
occurring during the withering process and in general improve the nutraceutical
properties of grapes and wines. On the other hand, longer processes showed to
decrease flavan-3-ols and glycoside flavonols. Constant increase of E/Z epsilon
viniferin ratio was observed in all samples, and this parameter can be used to
monitor the process. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27491022
TI - Molecular characterization and functional analysis of pheromone binding protein 1
from Cydia pomonella (L.).
AB - A full-length cDNA encoding Cydia pomonella pheromone binding protein 1
(CpomPBP1) was cloned and characterized. CpomPBP1, possessing the typical
characteristics of lepidopteran odorant binding proteins, was detected to be
specifically expressed in the antennae of male and female moths at the mRNA and
protein level. Soluble recombinant CpomPBP1 was subjected to in vitro binding to
analyse its binding properties and to search for potentially active
semiochemicals. A competitive binding assay showed that three 12-carbon ligands,
codlemone, 1-dodecanol and E,E-2,4-dodecadienal, were able to bind to CpomPBP1 in
decreasing order of affinity. Moreover, unlike the wild-type CpomPBP1, the C
terminus truncated CpomPBP1 exhibited high affinity to ligands even in an acidic
environment, suggesting that the C-terminus plays a role in preventing ligands
from binding to CpomPBP1 in a lower pH environment.
PMID- 27491021
TI - Structural basis for cholinergic regulation of neural circuits in the mouse
olfactory bulb.
AB - Odor information is regulated by olfactory inputs, bulbar interneurons, and
centrifugal inputs in the olfactory bulb (OB). Cholinergic neurons projecting
from the nucleus of the horizontal limb of the diagonal band of Broca and the
magnocellular preoptic nucleus are one of the primary centrifugal inputs to the
OB. In this study, we focused on cholinergic regulation of the OB and analyzed
neural morphology with a particular emphasis on the projection pathways of
cholinergic neurons. Single-cell imaging of a specific neuron within dense fibers
is critical to evaluate the structure and function of the neural circuits. We
labeled cholinergic neurons by infection with virus vector and then reconstructed
them three-dimensionally. We also examined the ultramicrostructure of synapses by
electron microscopy tomography. To further clarify the function of cholinergic
neurons, we performed confocal laser scanning microscopy to investigate whether
other neurotransmitters are present within cholinergic axons in the OB. Our
results showed the first visualization of complete cholinergic neurons, including
axons projecting to the OB, and also revealed frequent axonal branching within
the OB where it innervated multiple glomeruli in different areas. Furthermore,
electron tomography demonstrated that cholinergic axons formed asymmetrical
synapses with a morphological variety of thicknesses of the postsynaptic density.
Although we have not yet detected the presence of other neurotransmitters, the
range of synaptic morphology suggests multiple modes of transmission. The present
study elucidates the ways that cholinergic neurons could contribute to the
elaborate mechanisms involved in olfactory processing in the OB. J. Comp. Neurol.
525:574-591, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27491023
TI - Tyrosine Kinase Inhibitors. 20. Optimization of Substituted Quinazoline and
Pyrido[3,4-d]pyrimidine Derivatives as Orally Active, Irreversible Inhibitors of
the Epidermal Growth Factor Receptor Family.
AB - Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were
determined for a series of quinazoline- and pyrido[3,4-d]pyrimidine-based
analogues of the irreversible pan-erbB inhibitor, canertinib. Cyclic amine
bearing crotonamides were determined to provide rapid inhibition of cellular
erbB1 autophosphorylation and good metabolic stability in liver microsome and
hepatocyte assays. The influence of 4-anilino substitution on pan-erbB inhibitory
potency was investigated. Several anilines were identified as providing potent,
reversible pan-erbB inhibition. Optimum 4- and 6-substituents with known 7
substituents provided preferred irreversible inhibitors for pharmacodynamic
testing in vivo. Quinazoline 54 and pyrido[3,4-d]pyrimidine 71 were identified as
clearly superior to canertinib. Both compounds possess a piperidinyl crotonamide
Michael acceptor and a 3-chloro-4-fluoroaniline, indicating these as optimized 6-
and 4-substituents, respectively. Pharmacokinetic comparison of compounds 54 and
71 across three species selected compound 54 as the preferred candidate. Compound
54 (PF-00299804) has been assigned the nomenclature of dacomitinib and is
currently under clinical evaluation.
PMID- 27491025
TI - 5-year follow-up of a randomized clinical study comparing everolimus plus reduced
dose cyclosporine with mycophenolate mofetil plus standard-dose cyclosporine in
de novo kidney transplantation: Retrospective single center assessment.
AB - The aim of this study is to evaluate the efficacy and safety of everolimus plus
reduced-dose cyclosporine compared with mycophenolate mofetil plus standard-dose
cyclosporine 5years after living donor kidney transplantation. Between March 2008
and August 2009, 24 living donor kidney transplantations were enrolled in a 2
year, multicenter, randomized phase 3 study (RAD001A1202 study). 24 recipients
were randomly classified into two groups and closely observed for 5years. 13
recipients were administered steroid, reduced-dose cyclosporine, everolimus and
basiliximab (EVR group). 11 recipients were administered steroid, standard-dose
cyclosporine, mycophenolate mofetil and basiliximab (STD group). Two groups were
compared not only in graft function including estimated glomerular filtration
rate (eGFR), and proteinuria, but also in adverse events such as de novo donor
specific antibody (DSA) production, rejection, new-onset diabetes,
hyperlipidemia, and cytomegalovirus (CMV) infection. No graft loss was identified
in 5years. The incidences of acute T cell rejection, de novo DSA production,
hyperlipidemia, and new-onset diabetes were similar. eGFR levels throughout the
observation periods were similar. Three cases of proteinuria were identified in
STD group. One case of proteinuria observed in EVR group was well controlled with
angiotensin receptor blocker. Incidence of CMV infection in CMV antibody-positive
recipients was significantly lower in EVR group. The safety and efficacy of
reduced-dose cyclosporine and everolimus protocol were similar to those of
standard-dose cyclosporine and mycophenolate mofetil other than for superior
prevention of CMV infection.
PMID- 27491026
TI - A Comparative Study of Intratesticular Ductules in the Spermatogenically Active
Testes of Shortfin Mako and Thresher Sharks.
AB - This comparative study of the radial testes of sexually mature thresher sharks
(Alopias vulpinus) and shortfin mako sharks (Isurus oxyrinchus) describes the
histology of the three-tiered network of sperm-carrying ductules in the testis
and the lymphomyeloid tissue associated with it, namely the epigonal organ. In
both species, a testis -> epigonal gradient was evident regarding the thickness
of the ductule epithelial lining and subepithelial investment of connective
tissue. Ductules straddling the testis-epigonal border often displayed luminal
leukocytes and various signs of regression, including the progressive thickening
of the ductule epithelial lining, dissolution of the cytoplasm, and loss of
normal histoarchitecture. In Isurus, large amorphous areas formed due to the
fusion of neighboring regressing ductules. The epigonal organ of Alopias
additionally revealed circular degenerative sperm-containing, Hassall-like bodies
with either a degenerate or cellular appearance, the latter the result of cell
proliferative activity (as shown by proliferating cell nuclear antigen (PCNA)
immunohistochemistry) in an expanding outer border comprising cells with
intensely PCNA immunoreactive slender and oblong nuclei. The latter cells
exhibited a periphery-to-center transformation of their nuclei, at which stage
they were PCNA-negative and most likely in a terminally differentiated state as
they phagocytized the cell debris in the degenerate core. Intermediate stages of
these circular bodies were a rarity. The relationship between these degenerate
bodies, and the common occurrence of blind pockets in the epithelial linings and
non-apoptosis-related degenerate patches in the apical cytoplasmic regions of the
irregular shaped ductules in Alopias is unclear, and needs further elucidation.
Anat Rec, 299:1435-1448, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27491024
TI - Deletion of FoxO1, 3, and 4 in Osteoblast Progenitors Attenuates the Loss of
Cancellous Bone Mass in a Mouse Model of Type 1 Diabetes.
AB - Type 1 diabetes is associated with osteopenia and increased fragility fractures,
attributed to reduced bone formation. However, the molecular mechanisms mediating
these effects remain unknown. Insulin promotes osteoblast formation and inhibits
the activity of the FoxO transcription factors. FoxOs, on the other hand, inhibit
osteoprogenitor proliferation and bone formation. Here, we investigated whether
FoxOs play a role in the low bone mass associated with type 1 diabetes, using
mice lacking FoxO1, 3, and 4 in osteoprogenitor cells (FoxO1,3,4DeltaOsx1-Cre ).
Streptozotocin-induced diabetes caused a reduction in bone mass and strength in
FoxO-intact mice. In contrast, cancellous bone was unaffected in diabetic
FoxO1,3,4DeltaOsx1-Cre mice. The low bone mass in the FoxO-intact diabetic mice
was associated with decreased osteoblast number and bone formation, as well as
decreased expression of the anti-osteoclastogenic cytokine osteoprotegerin (OPG)
and increased osteoclast number. FoxO deficiency did not alter the effects of
diabetes on bone formation; however, it did prevent the decrease in OPG and the
increase in osteoclast number. Addition of high glucose to osteoblastic cell
cultures decreased OPG mRNA, indicating that hyperglycemia in and of itself
contributes to diabetic bone loss. Taken together, these results suggest that
FoxOs exacerbate the loss of cancellous bone mass associated with type 1 diabetes
and that inactivation of FoxOs might ameliorate the adverse effects of insulin
deficiency. (c) 2016 American Society for Bone and Mineral Research.
PMID- 27491027
TI - Detailed analysis of adverse events and surgical interventions in a large
prospective trial of sacral neuromodulation therapy for overactive bladder
patients.
AB - INTRODUCTION: The InSite trial is a prospective, multicenter study of sacral
neuromodulation (SNM) therapy with the InterStim(r) System in subjects with
overactive bladder (OAB). One of the primary aims of the study is to report on
long-term safety of the tined lead. This analysis provides detailed descriptions
of device-related adverse events (AEs) and surgical interventions to 12 months.
METHODS: Analysis included those subjects who completed test stimulation with a
tined lead, received a full implant, and reported device-related AEs out to 12
months. A Clinical Events Committee (CEC) adjudicated AEs to 12 months. RESULTS:
Device-related AEs occurred in 30% (82/272) of subjects, with only one considered
serious. Fifty-six percent of the device-related AEs occurred between implant and
3 months. The most frequent device-related AEs were undesirable change in
stimulation (12%, 32/272); implant site pain (7%, 20/272); and implant site
infection (3%, 9/272). Of the 26 events of implant site pain, 13 required
surgical intervention, with only two resulting in explant. Ten subjects
experienced 13 events of a surgical site infection (including an additional
cellulitis), five of which resolved with antibiotics and eight required
explantation. The overall surgical intervention rate was 13% with the most common
reasons being pain at the surgical site (4%), lack/loss of efficacy (4%), and
infection (3%). CONCLUSIONS: Although a 30% AE rate was reported, most AEs were
minor and were resolved without surgical intervention. Surgical intervention was
required in 13% of subjects, with the majority being revision or replacement.
Neurourol. Urodynam. 36:1136-1139, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27491028
TI - Assessment of the capability of remote sensing and GIS techniques for monitoring
reclamation success in coal mine degraded lands.
AB - The objective of the present study is to monitor reclamation activity in mining
areas. Monitoring of these reclaimed sites in the vicinity of mining areas and on
closed Over Burden (OB) dumps is critical for improving the overall environmental
condition, especially in developing countries where area around the mines are
densely populated. The present study evaluated the reclamation success in the
Block II area of Jharia coal field, India, using Landsat satellite images for the
years 2000 and 2015. Four image processing methods (support vector machine, ratio
vegetation index, enhanced vegetation index, and normalized difference vegetation
index) were used to quantify the change in vegetation cover between the years
2000 and 2015. The study also evaluated the relationship between vegetation
health and moisture content of the study area using remote sensing techniques.
Statistical linear regression analysis revealed that Normalized Difference
Vegetation Index (NDVI) coupled with Normalized Difference Moisture Index (NDMI)
is the best method for vegetation monitoring in the study area when compared to
other indices. A strong linear relationship (r(2) > 0.86) was found between NDVI
and NDMI. An increase of 21% from 213.88 ha in 2000 to 258.9 ha in 2015 was
observed in the vegetation cover of the reclaimed sites for an open cast mine,
indicating satisfactory reclamation activity. NDVI results indicated that
vegetation health also improved over the years.
PMID- 27491029
TI - Protective effect of gelatin polypeptides from Pacific cod (Gadus macrocephalus)
against UV irradiation-induced damages by inhibiting inflammation and improving
transforming growth factor-beta/Smad signaling pathway.
AB - Exposure to ultraviolet (UV) radiation results in skin damage, collagen reduction
in the dermis, and consequently, premature skin aging (photoaging). The goal of
this study was to examine the effect of gelatin hydrolysate (CH) from pacific cod
(Gadus macrocephalus) skin on UV irradiation-induced inflammation and collagen
reduction of photoaging mouse skin. The effect of CH on the activities of
endogenous antioxidant enzymes was investigated. The expressions of nuclear
factor-kappaB (NF-kappaB), proinflammatory cytokines, type I and type III
procollagen, transforming growth factor-beta1 (TGF-beta1), type II receptor of
TGF-beta1 (TGF-betaRII), and Smad7 were determined using quantitative real-time
reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. The results
showed that oral administration of CH suppressed UV irradiation-induced damages
to skin by inhibiting the depletion of endogenous antioxidant enzyme activity,
and by suppressing the expression of NF-kappaB as well as NF-kappaB-mediated
proinflammatory cytokines expression. Furthermore, CH inhibited type I
procollagen synthesis reduction by up-regulating TbetaRII level and down
regulating Smad7 level, which demonstrates that CH is involved in matrix collagen
synthesis by activating the TGF-beta/Smad pathway in the photoaging skin. Based
on these results, we conclude that CH protected skin from UV irradiation-induced
photodamages, and CH may be a potentially effective agent for the prevention of
photoaging.
PMID- 27491030
TI - Application of UV-Vis spectrophotometric process for the assessment of
indoloacridines as free radical scavenger.
AB - A conventional approach has been used to synthesis Indole fused acridine, 4a-e.
In this paper to achieve the target molecule, 4 the reaction was performed via
two steps. In step 1, there was a reaction between Carbazolone, 1 and
benzophenone, 2 to get dihydroindoloacridine, 3. In step 2, compound, 3 was
treated with 5% Palladium/Carbon in the presence of diphenyl ether for 5h to give
a dark brown product, 4. The column chromatography was used to purify final
product, 4. All the synthesized compounds such as 3 and 4 were characterized by
melting point, FTIR, (1)H NMR, and Mass spectra. Further to check the purity of
the compounds it was subjected to CHN analyzer. The target molecules such as 3
and 4 were screened for antimicrobial studies against bacteria such as Bacillus
subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Klebsiella pneumonia
(K. pneumonia), Salmonella typhi (S. typhi); and fungi like Aspergillus niger (A.
niger), Aspergillus fumigatus (A. fumigatus). The obtained results clearly proves
that the target molecules shown reasonable activity against K. pneumonia and A.
niger. Further the compounds were screened for free radical scavenging activity
using 2,2-diphenyl-1-picrylhydrazyl (DPPH). The free radical scavenging property
was performed using UV-Visible spectroscopy. The results were compared with the
standard BHT (Butylated Hydroxy Toluene). Compounds, 4a and 4e were shown higher
percentage of inhibition when compare to the standard. The result confirms that
further research on indoloacridine will leads effective drug to the market.
PMID- 27491031
TI - One-pot biogenic fabrication of silver nanocrystals using Quisqualis indica:
Effectiveness on malaria and Zika virus mosquito vectors, and impact on non
target aquatic organisms.
AB - Currently, mosquito vector control is facing a number of key challenges,
including the rapid development of resistance to synthetic pesticides and the
recent spread of aggressive arbovirus outbreaks. The biosynthesis of silver
nanoparticles (AgNPs) is currently considered an environmental friendly
alternative to the employ of pyrethroids, carbamates and microbial agents (e.g.
Bacillus thuringiensis var. israelensis), since AgNPs are easy to produce,
effective and stable in the aquatic environment. However, their biophysical
features showed wide variations according to the botanical agent using for the
green synthesis, outlining the importance of screening local floral resources
used as reducing and stabilizing agents. In this study, we focused on the
biophysical properties and the mosquitocidal action of Quisqualis indica
fabricated AgNPs. AgNPs were characterized using spectroscopic (UV, FTIR, XRD)
and microscopic (AFM, SEM, TEM and EDX) techniques. AFM, SEM and TEM confirmed
the synthesis of poly-dispersed AgNPs with spherical shape and size ranging from
1 to 30nm. XRD shed light on the crystalline structure of these AgNPs. The acute
toxicity of Quisqualis indica extract and AgNPs was evaluated against malaria,
arbovirus, and filariasis vectors, Anopheles stephensi, Aedes aegypti and Culex
quinquefasciatus, as well as on three important non-target aquatic organisms. The
Q. indica leaf extract showed moderate larvicidal effectiveness on Cx.
quinquefasciatus (LC50=220.42), Ae. aegypti (LC50=203.63) and An. stephensi
(LC50=185.98). Q. indica-fabricated AgNPs showed high toxicity against Cx.
quinquefasciatus (LC50=14.63), Ae. aegypti (LC50=13.55) and An. stephensi
(LC50=12.52), respectively. Notably, Q. indica-synthesized AgNPs were moderately
toxic to non-target aquatic mosquito predators Anisops bouvieri
(LC50=653.05MUg/mL), Diplonychus indicus (LC50=860.94MUg/mL) and Gambusia affinis
(LC50=2183.16MUg/mL), if compared to the targeted mosquitoes. Overall, the
proposed one-pot biogenic fabrication of AgNPs using Q. indica is a low-cost and
eco-friendly tool in the fight against Zika virus, malaria and filariasis
vectors, with little impact against non-target aquatic mosquito predators.
PMID- 27491032
TI - Predicting Melting Points of Organic Molecules: Applications to Aqueous
Solubility Prediction Using the General Solubility Equation.
AB - In this work we make predictions of several important molecular properties of
academic and industrial importance to seek answers to two questions: 1) Can we
apply efficient machine learning techniques, using inexpensive descriptors, to
predict melting points to a reasonable level of accuracy? 2) Can values of this
level of accuracy be usefully applied to predicting aqueous solubility? We
present predictions of melting points made by several novel machine learning
models, previously applied to solubility prediction. Additionally, we make
predictions of solubility via the General Solubility Equation (GSE) and monitor
the impact of varying the logP prediction model (AlogP and XlogP) on the GSE. We
note that the machine learning models presented, using a modest number of 2D
descriptors, can make melting point predictions in line with the current state of
the art prediction methods (RMSE>=40 degrees C). We also find that predicted
melting points, with an RMSE of tens of degrees Celsius, can be usefully applied
to the GSE to yield accurate solubility predictions (log10 S RMSE<1) over a small
dataset of drug-like molecules.
PMID- 27491033
TI - Adaptive Particle Swarm Optimizer with Varying Acceleration Coefficients for
Finding the Most Stable Conformer of Small Molecules.
AB - A novel parameter automation strategy for Particle Swarm Optimization called APSO
(Adaptive PSO) is proposed. The algorithm is designed to efficiently control the
local search and convergence to the global optimum solution. Parameters c1
controls the impact of the cognitive component on the particle trajectory and c2
controls the impact of the social component. Instead of fixing the value of c1
and c2 , this paper updates the value of these acceleration coefficients by
considering time variation of evaluation function along with varying inertia
weight factor in PSO. Here the maximum and minimum value of evaluation function
is use to gradually decrease and increase the value of c1 and c2 respectively.
Molecular energy minimization is one of the most challenging unsolved problems
and it can be formulated as a global optimization problem. The aim of the present
paper is to investigate the effect of newly developed APSO on the highly complex
molecular potential energy function and to check the efficiency of the proposed
algorithm to find the global minimum of the function under consideration. The
proposed algorithm APSO is therefore applied in two cases: Firstly, for the
minimization of a potential energy of small molecules with up to 100 degrees of
freedom and finally for finding the global minimum energy conformation of 1,2,3
trichloro-1-flouro-propane molecule based on a realistic potential energy
function. The computational results of all the cases show that the proposed
method performs significantly better than the other algorithms.
PMID- 27491034
TI - Prediction of Nucleotide Binding Peptides Using Star Graph Topological Indices.
AB - The nucleotide binding proteins are involved in many important cellular
processes, such as transmission of genetic information or energy transfer and
storage. Therefore, the screening of new peptides for this biological function is
an important research topic. The current study proposes a mixed methodology to
obtain the first classification model that is able to predict new nucleotide
binding peptides, using only the amino acid sequence. Thus, the methodology uses
a Star graph molecular descriptor of the peptide sequences and the Machine
Learning technique for the best classifier. The best model represents a Random
Forest classifier based on two features of the embedded and non-embedded graphs.
The performance of the model is excellent, considering similar models in the
field, with an Area Under the Receiver Operating Characteristic Curve (AUROC)
value of 0.938 and true positive rate (TPR) of 0.886 (test subset). The
prediction of new nucleotide binding peptides with this model could be useful for
drug target studies in drug development.
PMID- 27491035
TI - Streptococcus pneumoniae Genome-wide Identification and Characterization of BOX
Element-binding Domains.
AB - The BOX elements are short repetitive DNA sequences that distribute randomly in
intergenic regions of the Streptococcus pneumoniae genome. The function and
origin of such elements are still unknown, but they were found to modulate
expression of neighboring genes. Evidences suggested that the modulation's
mechanism can be fulfilled by sequence-specific interaction of BOX elements with
transcription factor family proteins. However, the type and function of these BOX
binding proteins still remain largely unexplored to date. In the current study we
described a synthetic protocol to investigate the recognition and interaction
between a highly conserved site of BOX elements and the DNA-binding domains of a
variety of putative transcription factors in the pneumococcal genome. With the
protocol we were able to predict those high-affinity domain binders of the
conserved BOX DNA site (BOX DNA) in a high-throughput manner, and analyzed
sequence-specific interaction in the domain?DNA recognition at molecular level.
Consequently, a number of putative transcription factor domains with both high
affinity and specificity for the BOX DNA were identified, from which the helix
turn-helix (HTH) motif of a small heat shock factor was selected as a case study
and tested for its binding capability toward the double-stranded BOX DNA using
fluorescence anisotropy analysis. As might be expected, a relatively high
affinity was detected for the interaction of HTH motif with BOX DNA with
dissociation constant at nanomolar level. Molecular dynamics simulation, atomic
structure examination and binding energy analysis revealed a complicated network
of intensive nonbonded interactions across the complex interface, which confers
both stability and specificity for the complex architecture.
PMID- 27491036
TI - Inferring Association between Compound and Pathway with an Improved Ensemble
Learning Method.
AB - Emergence of compound molecular data coupled to pathway information offers the
possibility of using machine learning methods for compound-pathway associations'
inference. To provide insights into the global relationship between compounds and
their affected pathways, a improved Rotation Forest ensemble learning method
called RGRF (Relief & GBSSL - Rotation Forest) was proposed to predict their
potential associations. The main characteristic of the RGRF lies in using the
Relief algorithm for feature extraction and regarding the Graph-Based Semi
Supervised Learning method as classifier. By incorporating the chemical structure
information, drug mode of action information and genomic space information, our
method can achieve a better precision and flexibility on compound-pathway
prediction. Moreover, several new compound-pathway associations that having the
potential for further clinical investigation have been identified by database
searching. In the end, a prediction tool was developed using RGRF algorithm,
which can predict the interactions between pathways and all of the compounds in
cMap database.
PMID- 27491037
TI - Improving tRNAscan-SE Annotation Results via Ensemble Classifiers.
AB - tRNAScan-SE is a tRNA detection program that is widely used for tRNA annotation;
however, the false positive rate of tRNAScan-SE is unacceptable for large
sequences. Here, we used a machine learning method to try to improve the tRNAScan
SE results. A new predictor, tRNA-Predict, was designed. We obtained real and
pseudo-tRNA sequences as training data sets using tRNAScan-SE and constructed
three different tRNA feature sets. We then set up an ensemble classifier,
LibMutil, to predict tRNAs from the training data. The positive data set of 623
tRNA sequences was obtained from tRNAdb 2009 and the negative data set was the
false positive tRNAs predicted by tRNAscan-SE. Our in silico experiments revealed
a prediction accuracy rate of 95.1 % for tRNA-Predict using 10-fold cross
validation. tRNA-Predict was developed to distinguish functional tRNAs from
pseudo-tRNAs rather than to predict tRNAs from a genome-wide scan. However, tRNA
Predict can work with the output of tRNAscan-SE, which is a genome-wide scanning
method, to improve the tRNAscan-SE annotation results. The tRNA-Predict web
server is accessible at http://datamining.xmu.edu.cn/~gjs/tRNA-Predict.
PMID- 27491038
TI - Targeting Yes-associated Protein with Evolved Peptide Aptamers to Disrupt TGF
beta Signaling Pathway: Therapeutic Implication for Bone Tumor.
AB - The binding of transcription coactivator Yes-associated protein (YAP) to Smad
transcription factors is an important event in activating transforming growth
factor-beta (TGF-beta) signaling pathway, which is involved in the tumorigenicity
and metastasis of bone tumor. Design of peptide aptamers to disrupt YAP?Smad
interaction has been established as a promising approach for bone tumor therapy.
Here, an evolution strategy was used to optimize Smad-derived peptides for high
potency binding to YAP WW2 domain, resulting in an improved peptide population,
from which those high-scoring candidates were characterized rigorously using
molecular dynamics (MD) simulations and interaction free energy calculations.
With the computational protocol we were able to generate a number of potential
domain binders, which were then substantiated by using fluorescence spectroscopy
assay. Subsequently, the complex structure of YAP WW2 domain with a high-affinity
peptide was modeled and examined in detail, which was then used to guide
structure-based peptide optimization to obtain several strong domain binders.
Structural and energetic analysis revealed that electrostatic complementarity is
primarily responsible for domain?peptide recognition, while other nonbonded
interactions such as hydrogen bonding and salt bridges can contribute
significantly to the recognition specificity.
PMID- 27491039
TI - Variable sensory nerve conduction parameters in late onset Friedreich ataxia.
PMID- 27491040
TI - Akt mediates TIGAR induction in HeLa cells following PFKFB3 inhibition.
AB - Neoplastic cells metabolize higher amounts of glucose relative to normal cells in
order to cover increased energetic and anabolic needs. Inhibition of the
glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3)
diminishes cancer cell proliferation and tumour growth in animals. In this work,
we investigate the crosstalk between PFKFB3 and TIGAR (TP53-Induced Glycolysis
and Apoptosis Regulator), a protein known to protect cells from oxidative stress.
Our results show consistent TIGAR induction in HeLa cells in response to PFKFB3
knockdown. Upon PFKFB3 silencing, cells undergo oxidative stress and trigger Akt
phosphorylation. This leads to induction of a TIGAR-mediated prosurvival pathway
that reduces both oxidative stress and cell death. As TIGAR is known to have a
role in DNA repair, it could serve as a potential target for the development of
effective antineoplastic therapies.
PMID- 27491041
TI - Diagnostic and Therapeutic Challenges.
PMID- 27491042
TI - PERIPHERAL RETINAL VASCULITIS: Analysis of 110 Consecutive Cases and a
Contemporary Reappraisal of Tubercular Etiology.
AB - PURPOSE: Describe the clinical features and outcomes of patients with peripheral
retinal vasculitis (RV) and describe clinical characteristics of presumed
tubercular RV in a nonendemic setting. METHODS: Retrospective cohort study of 110
consecutive patients with peripheral RV at a tertiary referral eye care center in
the United Kingdom. Retinal vasculitis was defined as RV with vitritis associated
with peripheral retinal ischemia. Patients who also had positive Quantiferon Gold
in Tube test, positive tuberculin skin test, and/or other evidence of systemic
tuberculosis such as biopsy were labeled with presumed tubercular RV. Treatment
success was defined as resolution of inflammation, and successful tapering of
oral corticosteroids to less than 10 mg/day or topical steroids to less than
twice a day. RESULTS: Mean age of the study population was 42.69 +/- 14.95 years.
Patients were predominantly Asian (49.1%) and Male (67.0%). A total of 73.2% had
bilateral involvement. Sixty-nine (62.72%) patients had presumed tubercular RV. A
total of 52.8% patients received antitubercular therapy, 65.5% received oral
corticosteroids, and 17.3% required steroid-sparing oral immunosuppressive
agents. A total of 85.19% of patients with presumed tubercular RV achieved
treatment success with concurrent antitubercular therapy as against 75.61% of
patients with nontubercular RV. CONCLUSION: This is the largest study of the
epidemiology, clinical features, and outcomes of both peripheral RV and presumed
tubercular RV to date. Presumed tubercular RV commonly seems to affect young
males of Asian descent and had vitreous hemorrhage as common clinical findings
and also demonstrated a good treatment outcome with antitubercular therapy.
PMID- 27491043
TI - METAMORPHOPSIA AND TANGENTIAL RETINAL DISPLACEMENT AFTER EPIRETINAL MEMBRANE
SURGERY.
AB - PURPOSE: To determine whether the degree of metamorphopsia significantly
correlated with the distance of the tangenital retinal displacement after
epiretinal membrane surgery. METHODS: The M-CHARTS were used to measure the
vertical metamorphopsia score and the horizontal score. The distances between the
intersections of two sets of retinal vessels situated vertically or horizontally
were measured in the near-infrared Spectralis images. RESULTS: Fifty eyes of 50
patients (22 men; age, 69.5 +/- 7.8 years) were retrospectively studied. The
vertical and horizontal metamorphopsia scores significantly improved at 1 month
after the surgery, and the vertical and horizontal retinal distances increased.
The baseline horizontal and vertical metamorphopsia scores significantly
correlated with the ratio of the pre- and postoperative vertical and horizontal
retinal displacements, respectively (P = 0.038 and P = 0.015 at 1 week; P = 0.036
and P = 0.036 at 1 month). The postoperative horizontal metamorphopsia score at 1
month and the vertical metamorphopsia score at 3 months significantly correlated
with the vertical displacement at 1 month (P = 0.034) and the horizontal
displacement at 3 months (P = 0.001), respectively. CONCLUSION: The degree of
metamorphopsia significantly correlated with the tangential retinal displacement.
Dislocated Muller cells may stimulate the photoreceptors located away from
original positions, which consequently results in the sensation of metamorphopsia
in patients with an epiretinal membrane.
PMID- 27491044
TI - CLOSING MACULAR HOLES WITH "MACULAR PLUG" WITHOUT GAS TAMPONADE AND POSTOPERATIVE
POSTURING.
AB - PURPOSE: To investigate the surgical results of macular hole surgery without gas
tamponade or postoperative posturing in patients with Stage 3 and Stage 4 macular
holes with >=500 MUm mean base diameter. DESIGN: Retrospective interventional
case series. PARTICIPANTS: Twenty-six patients with Stage 3 and Stage 4 macular
holes. METHODS: Twenty-six eyes of 26 patients with Stage 3 and Stage 4 macular
holes and a mean base diameter of 892.8 +/- 349 MUm underwent pars plana 23-gauge
vitrectomy with broad internal limiting membrane peel (ILM peel), inverted ILM
flap repositioning (ILMR), and use of autologous gluconated blood clumps as a
macular plug to close the macular hole. No fluid-air exchange, endotamponade, or
postoperative posturing was used. The subjects were followed up for 12 months.
The anatomical outcome of the procedure was evaluated by fundus examination and
optical coherence tomography. Spectral domain optical coherence tomography was
used to study the restoration of the outer retinal layer integrity in the
postoperative period. The preoperative and postoperative best-corrected visual
acuities in logMAR units were compared to evaluate functional outcome. MAIN
OUTCOME MEASURE: Macular hole closure and best-corrected visual acuity before and
after surgery. RESULTS: Twenty-six patients with mean age 62.8 +/- 7.3 years,
preoperative median best-corrected visual acuity 6/60 (1.0 logMAR units), and a
mean base diameter of 892.8 +/- 349 MUm underwent surgery to close macular holes
without gas tamponade or postoperative posturing. Twenty patients (76.9%) were
phakic. Twenty eyes (76.92%) had Stage 3 macular holes and 6 eyes (23.10%) had
Stage 4 macular holes. After a single surgery, hole closure was achieved in 100%
of eyes. The median best-corrected visual acuity improved from 6/60 (1.0 logMAR
units) to 6/18 (0.50 logMAR units) (P < 0.001). Three patients needed cataract
surgery at 12-month follow-up. No major intraoperative or postoperative
complications were observed. CONCLUSION: Twenty-three-gauge pars plana vitrectomy
combined with broad ILM peeling, use of ILMR and autologous gluconated blood
clumps as a macular plug is effective in achieving satisfactory hole closure with
statically significant functional improvement for large Stage 3 and Stage 4
macular holes.
PMID- 27491045
TI - Leukemic Optic Nerve Infiltration Complicated by Retinal Artery and Vein
Occlusions.
PMID- 27491046
TI - CLINICAL EVALUATION OF THE RAPID ACCESS VITREAL INJECTION GUIDE: A Handheld
Instrument for Assisting Intravitreal Injections.
AB - PURPOSE: The Rapid Access Vitreal Injection (RAVI) guide combines the function of
an eyelid speculum and measuring caliper into a single instrument for assisting
intravitreal injections. This study clinically evaluated the RAVI guide with
respect to patient acceptance, complication rates, and operative goals. METHODS:
A prospective study was performed on 54 patients undergoing intravitreal
injections using the RAVI guide (n = 32) or the speculum/caliper (n = 22). Device
related pain was assessed using the Wong-Baker scoring system, scaled from 0 (no
pain) to 10 (agonizing pain). RESULTS: Mean device-related pain score did not
differ significantly between the 2 groups, with scores of 0.6 and 0.7 for the
RAVI guide and speculum groups, respectively. The rate of significant pain (score
of >=2) was twice as high in the speculum group (7 of 22, 32%) compared with the
RAVI guide group (5 of 32, 16%), but this difference was not statistically
significant (P = 0.19, Fisher's exact test). Operative goals of avoiding needle
touch to lashes/lids and guiding needle insertion to the intended site were
achieved in all patients. CONCLUSION: The RAVI guide appeared equivalent to the
eyelid speculum in achieving operative goals, with similarly low pain scores. It
has the potential for facilitating efficient, accurate, and safe intravitreal
injections.
PMID- 27491048
TI - Long-term Results of Combined Rhinoplasty and Septal Perforation Repair.
AB - Importance: Combined rhinoplasty and septal perforation repair is a technically
challenging procedure, and few studies have reported the outcomes. Objective: To
present the long-term surgical results of rhinoplasty with concurrent septal
perforation repair. Design, Setting, and Participants: This retrospective study
included 17 patients who underwent rhinoplasty with concurrent septal perforation
repair at a tertiary academic medical center from March 2005, through March 2015.
Patients had a mean postoperative follow-up duration of 50.9 months. The etiology
of the deformity, presenting symptoms, perforation size, intraoperative surgical
techniques, and complications were analyzed. Final follow-up was completed on
March 31, 2015. Main Outcomes and Measures: Postoperative subjective (telephone
survey of patient satisfaction) and objective (Objective Rhinoplasty Outcome
Score) patient satisfaction and endoscopic nasal cavity examination at the last
follow-up. Results: Among the 17 patients (14 men; 3 women; mean [SD] age, 40
[16] years), 12 (71%) had previously undergone septoplasty and/or
septorhinoplasty, 4 (24%) had nasal trauma, and 1 (6%) had an unknown cause. The
main aesthetic reasons for rhinoplasty were a saddle nose deformity (10 patients
[59%]) and deviated nose related to a previous surgery or trauma (5 patients
[29%]). The functional reasons for surgery included nasal obstruction (14
patients [82%]) crusting (2 patients [12%]), epistaxis (1 patient [6%]), and
whistling (1 patient [6%]). The perforation size varied from 2 to 30 mm, with a
mean of 14.3 mm. Surgery was performed through the open rhinoplasty approach.
Perforations were first closed with an advancement flap in 6 patients, rotation
flap in 6 patients, a combination of both in 4 patients, and a combination of
advancement flap and free mucosal graft in 1 patient, with or without
interposition grafts. Rhinoplasty was performed with various grafts, maneuvers,
and septal reconstruction. Complete closure with symptom relief was achieved in
15 patients (88%). The mean objective score evaluating the rhinoplasty results
was 3.4 (on a scale of 0-4, where 3.4 is good to excellent). No serious
complications occurred after surgery. Conclusions and Relevance: Concurrent
rhinoplasty and nasal septal perforation repair is a safe and effective option
when necessary. The open rhinoplasty approach facilitated septal perforation
closure, whereas septal perforation repair did not affect the surgical result of
rhinoplasty. Level of Evidence: 4.
PMID- 27491049
TI - Recreational marijuana use is not associated with worse outcomes after renal
transplantation.
AB - As marijuana (MJ) legalization is increasing, kidney transplant programs must
develop listing criteria for marijuana users. However, no data exist on the
effect of MJ on kidney allograft outcomes, and there is no consensus on whether
MJ use should be a contraindication to transplantation. We retrospectively
reviewed 1225 kidney recipients from 2008 to 2013. Marijuana use was defined by
positive urine toxicology screen and/or self-reported recent use. The primary
outcome was death at 1 year or graft failure (defined as GFR<20 mL/min/1.73 m2 ).
The secondary outcome was graft function at 1 year. Using logistic regression
analyses, we compared these outcomes between MJ users and non-users. Marijuana
use was not associated with worse primary outcomes by unadjusted (odds ratio
1.07, 95% CI 0.45-2.57, P=.87) or adjusted (odds ratio 0.79, 95% CI 0.28-2.28,
P=.67) analysis. Ninety-two percent of grafts functioned at 1 year. Among these,
the mean creatinine (1.52, 95% CI 1.39-1.69 vs 1.46, 95% CI 1.42-1.49; P=.38) and
MDRD GFR (50.7, 95% CI 45.6-56.5 vs 49.5, 95% CI 48.3-50.7; P=.65) were similar
between groups. Isolated recreational MJ use is not associated with poorer
patient or kidney allograft outcomes at 1 year. Therefore, recreational MJ use
should not necessarily be considered a contraindication to kidney
transplantation.
PMID- 27491050
TI - Genomics- and Transcriptomics-Based Patient Selection for Cancer Treatment With
Immune Checkpoint Inhibitors: A Review.
AB - Importance: Checkpoint blockade therapy targeting cytotoxic T-lymphocyte
associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathways
(PD-1/PD-L1) have achieved success in treating a number of malignancies. However,
only a subset of patients responds to these therapies, and optimization of
patient selection for treatment is imperative to avoid adverse effects without
clinical benefit and keep costs manageable. Observations: The past few years have
witnessed checkpoint inhibition becoming a first-line treatment option with US
Food and Drug Administration approvals for various tumor types. Genomic analyses
(whole genome, exome, and transcriptome) have been instrumental in identifying a
genetic profile associated with sensitivity to checkpoint inhibitors. Therapy
outcome is determined at various levels: (1) the degree of tumor "foreignness,"
as reflected by mutational burden and expression of viral genes, (2) the
composition and activity of a preexisting immune infiltrate, and (3) mechanisms
of tumor escape from immune surveillance. In addition, there are opportunities
for genomic analyses of genetic polymorphisms and the gut microbiome that may be
associated with clinical response to therapy. Conclusions and Relevance: Genomics
provides powerful tools for the identification of biomarkers for response to
immune checkpoint blockade, given their potential to analyze multiple parameters
simultaneously in an unbiased manner. This offers the opportunity for genomics-
and transcriptomics-based selection of patients for rationally designed therapy
with immune checkpoint inhibitors.
PMID- 27491051
TI - Concurrent validity and reliability of using ground reaction force and center of
pressure parameters in the determination of leg movement initiation during single
leg lift.
AB - Postural adjustment evaluations during single leg lift requires the initiation of
heel lift (T1) identification. T1 measured by means of motion analyses system is
the most reliable approach. However, this method involves considerable workspace,
expensive cameras, and time processing data and setting up laboratory. The use of
ground reaction forces (GRF) and centre of pressure (COP) data is an alternative
method as its data processing and setting up is less time consuming. Further,
kinetic data is normally collected using frequency samples higher than 1000Hz
whereas kinematic data are commonly captured using 50-200Hz. This study describes
the concurrent-validity and reliability of GRF and COP measurements in
determining T1, using a motion analysis system as reference standard. Kinematic
and kinetic data during single leg lift were collected from ten participants. GRF
and COP data were collected using one and two force plates. Displacement of a
single heel marker was captured by means of ten Vicon((c)) cameras. Kinetic and
kinematic data were collected using a sample frequency of 1000Hz. Data were
analysed in two stages: identification of key events in the kinetic data, and
assessing concurrent validity of T1 based on the chosen key events with T1
provided by the kinematic data. The key event presenting the least systematic
bias, along with a narrow 95% CI and limits of agreement against the reference
standard T1, was the Baseline COPy event. Baseline COPy event was obtained using
one force plate and presented excellent between-tester reliability.
PMID- 27491052
TI - Postural instability in Charcot-Marie-Tooth 1A disease.
AB - The aim of this study was to evaluate the influence of somatosensory impairment,
distal muscle weakness and foot deformities on the balance in 21 CMT1A patients
using a baropodometric platform. Stabilometric analysis by measuring sway area
and velocity of a centre of pressure (CoP) both at open and closed eyes were used
to assess postural imbalance. Static analysis, by measuring the load and the
plantar surface of forefoot, midfoot and hindfoot was used to define the
footprint shape and to assess as a whole foot deformities. Stabilometric and
static results were compared with those of a control group. In CMT1A patients,
stabilometric findings were correlated with static parameters, Achilles' tendon
retraction, distal muscle strength and CMT examination score (CMTES). CMT1A
patients compared to controls had lower plantar surface and load on midfoot, and
higher load on a forefoot. CMT1A patients had a greater postural instability,
since they had a higher CoP velocity, both at open and closed eyes. Moreover, the
CoP velocity correlated inversely with the strength of ankle dorsi-flexion
muscles and directly with CMTES as whole and with the item "motor symptoms legs".
Postural imbalance was not correlated with sensory impairment and foot
deformities as expressed by static analysis and Achilles' tendon retraction. In
this study we demonstrated an altered balance in CMT1A patients during upright
standing. The imbalance in our CMT patients seems to be related to the weakness
of ankle dorsi-flexor muscles rather than sensory impairment or foot deformities.
These results could be due to a mildly affected CMT1A population, evaluated in an
early stage of the disease.
PMID- 27491053
TI - Hypokinetic gait changes induced by bilateral pallidal deep brain stimulation for
segmental dystonia.
AB - BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus internus (GPi)
has been established as an effective and safe treatment for dystonia. In general,
side effects are rare, but there is increasing evidence that GPi DBS in dystonia
can induce hypokinetic symptoms like micrographia or freezing of gait. We aimed
to evaluate and quantify possible changes of gait following bilateral chronic GPi
DBS for dystonia by computerized gait analyses. METHODS: We prospectively
performed computerized gait analysis in ten consecutive patients (mean age 57.8+/
14.3 years) with segmental dystonia but without involvement of lower trunk or
legs who were treated with bilateral GPi DBS. Using pressure sensitive insoles,
several parameters were measured preoperatively (pre-OP) and at a median of 7
months postoperatively. RESULTS: The mean step length significantly decreased
from 60.0+/-6.9cm pre-OP to 54.3+/-6.4cm with GPi DBS (p<0.01). Due to only small
changes of walking distance and gait velocity, the cadence correspondingly
increased from 105.6+/-9.2 steps/min to 111.3+/-11.4 steps/min (p<0.05). More
importantly, the variance of several gait parameters significantly decreased
postoperatively. CONCLUSIONS: In patients with segmental dystonia, chronic DBS of
the posteroventral lateral GPi is associated with only mild hypokinesia of gait,
but with a relevant decrease in gait variability. Given other recently reported
hypokinetic effects of GPi DBS for dystonia and recent results of
electrophysiological coherence studies, these findings support the hypothesis of
a general alteration of neuronal activity in striato-pallido-thalamo-cortical
motor pathways following chronic stimulation of the posteroventral lateral GPi.
PMID- 27491054
TI - Endoscopy Dyspnea and Ulcerative Colitis.
PMID- 27491055
TI - Prevalence of Diphyllobothrium latum (Cestoda: Diphyllobothriidae) plerocercoids
in fish species from four Italian lakes and risk for the consumers.
AB - In recent years there has been a re-emergence of diphyllobothriasis by
Diphyllobothrium latum (Cestoda: Diphyllobothriidae) in Italy, France and
Switzerland, where in the past this fish-borne zoonosis was widespread and then
virtually disappeared. A change in eating habits such as the consumption of
raw/undercooked freshwater fish, has led to an increased risk for consumers of
ingesting infective larvae of D. latum. A survey on the factors responsible for
the re-emergence of human diphyllobothriasis in Italy was carried out from March
2013 to December 2014. The aim of this study was to assess the diffusion of D.
latum plerocercoids in the fish populations of the sub-alpine lakes of Maggiore,
Como, Iseo and Garda, updating the scarce historical data and assessing a
preliminary "risk level" of the lacustrine environments and fish species under
investigation. A total of 2228 fish belonging to 5 species, 690 from Lake
Maggiore, 500 from Lake Como, 655 from Lake Iseo and 383 from Lake Garda were
submitted to parasitological examination. The presence of D. latum plerocercoid
larvae was detected in 6.6%, 25.4% and 7.6% of perch (Perca fluviatilis) from
Lakes Maggiore, Como and Iseo respectively. The parasite was also present in pike
(Esox lucius) with prevalence values ranging from 71.4 to 84.2% and in 3.6-3.8%
of burbot (Lota lota) from Lakes Iseo and Como. Fish from Lake Garda were
negative as well as sampled whitefish (Coregonus lavaretus) and shad (Alosa
fallax lacustris). The results of this survey showed a widespread presence of D.
latum plerocercoid larvae in Maggiore, Como and Iseo fish populations. Urban
fecal contamination of water is still a key issue to be resolved, together with
the improvement of communication with consumers regarding the best dietary habits
and the most effective processes of parasite inactivation, required for the
consumption of raw/undercooked fish caught in high-risk areas.
PMID- 27491057
TI - Magnetic Resonance Imaging of the Native Hip Joint.
PMID- 27491056
TI - Integrative taxonomy of Anisakidae and Raphidascarididae (Nematoda) in
Paralichthys patagonicus and Xystreurys rasile (Pisces: Teleostei) from Brazil.
AB - Thirty-six Paralichthys patagonicus and 30 Xystreurys rasile were collected in
the state of Rio de Janeiro, Brazil to investigate the presence of anisakid and
raphidascaridid nematodes. Anisakis typica, Terranova sp., Contracaecum sp.,
Hysterothylacium deardorffoverstreetorum, and Raphidascaris sp. were identified
using integrative taxonomy of morphological and genetic data. Morphological and
morphometric analysis was conducted using bright field microscopy with scanning
electron microscopy for topographic characterization of the cuticular surface.
Phylogenetic analysis, using ITS and cox2 molecular targets, clearly demonstrated
the species identification of A. typica and H. deardorffoverstreetorum and the
high diversity of H. deardorffoverstreetorum. This is the first report of A.
typica, H. deardorffoverstreetorum, and Raphidascaris sp. parasitizing P.
patagonicus and X. rasile.
PMID- 27491058
TI - An Introduction to Clinical Significance in Orthopaedic Outcomes Research.
PMID- 27491059
TI - Spine Surgery in an Ambulatory Setting: What Can Be Done Safely?
PMID- 27491060
TI - Proximal Interphalangeal Joint Arthroplasty: A Critical Analysis Review.
PMID- 27491061
TI - Intra-cochlear lipoma: a rare case diagnosed with specific magnetic resonance
imaging protocols.
PMID- 27491062
TI - CDC Grand Rounds: Adolescence - Preparing for Lifelong Health and Wellness.
AB - Approximately 42 million adolescents aged 10-19 years, representing 13% of the
population, resided in the United States in 2014 (1). Adolescence is
characterized by rapid and profound physical, intellectual, emotional, and
psychological changes (2), as well as development of healthy or risky behaviors
that can last a lifetime. Parents have strong influence on their adolescent
children's lives, and family-based programs can help parents support healthy
adolescent development. Because schools are natural learning environments,
implementing and improving school-based policies and programs are strategic ways
to reinforce healthy behaviors and educate adolescents about reducing risky
behaviors. Health care during adolescence should be tailored to meet the changing
developmental needs of the adolescent while providing welcoming, safe, and
confidential care. Parents, educators, care providers, public health officials,
and communities should collaborate in fostering healthy environments for all
adolescents, now and into the future.
PMID- 27491063
TI - [62]Tetradecaphyrin and Its Mono- and Bis-Zn(II) Complexes.
AB - A coiled structure of meso-pentafluorophenyl-substituted [62]tetradecaphyrin 1
was revealed by X-ray structural analysis. Synthetic protocols were devised to
form mono- and bis-Zn(II) complexes, 1 Zn and 1 Zn2 , selectively. The former
displayed a trigonal-bipyramidal pentacoordinated Zn(II) ion as a rare case and a
cyclic voltammogram exhibiting eleven reversible redox waves. The latter showed a
Ci-symmetric structure with modest Huckel aromaticity owing to a 62 pi-electronic
circuit as the largest aromatic molecule to date.
PMID- 27491064
TI - Direct Synthesis of Silylamine from N2 and a Silane: Mediated by a Tridentate
Phosphine Molybdenum Fragment.
AB - A homogeneous system which is able to yield silylamine from N2 and bis(silane) in
one pot is reported. Mechanistically a {(triphosphine)molybdenum(I)} fragment,
generated in situ, splits N2 into the corresponding nitrido complex at room
temperature. Then, functionalization of the molybdenum nitrido is achieved by
double Si-H addition under mild reaction conditions. Moreover, the
bis(silyl)amine product is decoordinated from the metal center.
PMID- 27491065
TI - Pre-clinical investigation of plasma pharmacokinetics and biodistribution of a
novel antithrombotic agent S002-333 in mice using LC-MS/MS.
AB - S002-333 [2-(4-methoxy-benzenesulfonyl)-2,3,4,9-tetrahydro-1H-b-carboxylic acid
amide] is a novel and potent antithrombotic agent developed by CSIR-CDRI, India.
The present study was aimed to develop a sensitive LC-MS/MS method for the
quantification of S002-333 in mice plasma and tissues. The extraction of S002-333
from relatively small amount of mouse biomatrices (50MUL) was accomplished using
protein precipitation followed by liquid-liquid extraction and the separation of
analytes was achieved on C18 reversed phase column using acetonitrile and triple
distilled water (75:25, v/v) as mobile phase at a flow rate of 0.6mL/min. The
instrument was operated in the multiple reaction monitoring (MRM) mode using
electrospray ionization (ESI) in the positive scan mode. For all the biomatrices,
linear relationship was attained over the concentration range of 0.39-200ng/mL
with correlation coefficients >=0.992. The lower limit of quantification for
mouse plasma and tissue homogenates was 0.39ng/mL. The bioanalytical method was
reproducible and reliable for all the matrices with inter-day and intra-day
variability in precision being less than 15% and accuracy within +/-15%. The
assay was successfully applied to pharmacokinetics and tissue distribution of
S002-333 in mice. The pharmacokinetic study revealed adequate gastrointestinal
absorption of S002-333 into the systemic circulation of mice with absolute oral
bioavailability of 45.8%. Tissue distribution data showed rapid and wide
distribution of S002-333 in the following order: small
intestine>liver>kidney~lungs>heart>spleen>brain. The present findings may provide
meaningful basis for further clinical development of this new chemical entity.
PMID- 27491066
TI - Teaching artificial intelligence to read electropherograms.
AB - Electropherograms are produced in great numbers in forensic DNA laboratories as
part of everyday criminal casework. Before the results of these electropherograms
can be used they must be scrutinised by analysts to determine what the identified
data tells us about the underlying DNA sequences and what is purely an artefact
of the DNA profiling process. A technique that lends itself well to such a task
of classification in the face of vast amounts of data is the use of artificial
neural networks. These networks, inspired by the workings of the human brain,
have been increasingly successful in analysing large datasets, performing medical
diagnoses, identifying handwriting, playing games, or recognising images. In this
work we demonstrate the use of an artificial neural network which we train to
'read' electropherograms and show that it can generalise to unseen profiles.
PMID- 27491067
TI - Transferring the blues: Depression-associated gut microbiota induces
neurobehavioural changes in the rat.
AB - The gut microbiota interacts with the host via neuroimmune, neuroendocrine and
neural pathways. These pathways are components of the brain-gut-microbiota axis
and preclinical evidence suggests that the microbiota can recruit this
bidirectional communication system to modulate brain development, function and
behaviour. The pathophysiology of depression involves neuroimmune-neuroendocrine
dysregulation. However, the extent to which changes in gut microbiota composition
and function mediate the dysregulation of these pathways is unknown. Thirty four
patients with major depression and 33 matched healthy controls were recruited.
Cytokines, CRP, Salivary Cortisol and plasma Lipopolysaccharide binding protein
were determined by ELISA. Plasma tryptophan and kynurenine were determined by
HPLC. Fecal samples were collected for 16s rRNA sequencing. A Fecal Microbiota
transplantation was prepared from a sub group of depressed patients and controls
and transferred by oral gavage to a microbiota-deficient rat model. We
demonstrate that depression is associated with decreased gut microbiota richness
and diversity. Fecal microbiota transplantation from depressed patients to
microbiota-depleted rats can induce behavioural and physiological features
characteristic of depression in the recipient animals, including anhedonia and
anxiety-like behaviours, as well as alterations in tryptophan metabolism. This
suggests that the gut microbiota may play a causal role in the development of
features of depression and may provide a tractable target in the treatment and
prevention of this disorder.
PMID- 27491068
TI - Effects of emotional acceptance and rumination on media-induced body
dissatisfaction in anorexia and bulimia nervosa.
AB - INTRODUCTION: Body dissatisfaction is an important risk and maintaining factor
for eating disorders. The aim of the present study was to experimentally test the
effects of two emotion regulation strategies - acceptance and rumination - on
media-induced body dissatisfaction in eating disorders. METHOD: After watching
pictures of thin models, women with anorexia nervosa (AN; n = 39) and bulimia
nervosa (BN; n = 39) were encouraged to either use emotional acceptance or
rumination to cope with their feelings. Body dissatisfaction and mood were
repeatedly assessed. RESULTS: Acceptance significantly improved body
dissatisfaction in women with BN. Rumination led to a significant increase of
body dissatisfaction in both eating disorder groups. Results were independent
from mood changes. DISCUSSION: Findings highlight the importance ruminative
thinking may have in the aggravation of dissatisfaction with the own body in AN
and BN. Results suggest that emotional acceptance is a useful strategy to
regulate body dissatisfaction after exposure to thin-ideal media in BN.
PMID- 27491069
TI - Association between seizures and mortality in patients with aneurysmal
subarachnoid hemorrhage: A nationwide retrospective cohort analysis.
AB - PURPOSE: The impact of seizures on outcomes in patients with subarachnoid
hemorrhage (SAH) is not well understood, with conflicting results published in
the literature. METHOD: For this retrospective cohort analysis, data from the
Nationwide Inpatient Samples (NIS) for 2006-2011 were utilized. All patients aged
>=18 years with a primary admitting diagnosis of subarachnoid hemorrhage were
included. Patients with a diagnosis of seizure were segregated from the initial
cohort. Multivariable logistic regression modeled the risk of death while
adjusting for severity of SAH as well as co-morbidities. The primary outcome of
this analysis was in-hospital mortality. RESULTS: 12,647 patients met inclusion
criteria for the study, of which 1336 had a diagnosis of seizures. The unadjusted
in-hospital mortality was higher for patients with seizures compared to those
without (16.2% vs 11.6%, p<0.01). Compared to patients without seizures, patients
with seizures were younger (52.4 years SD 13.9 vs 54.8 years, SD 13.6; p<0.01),
more likely to be male (35.6% vs 31.0%, p<0.01) and had longer hospital stays
(18.3 days, IQR 12.0-27.5 vs 14.8 days, IQR 10.0-21.9; p<0.01). After adjusting
for the severity of SAH, seizures were found to be associated with increased
mortality (OR 1.57, 95% CI 1.32-1.87, p<0.01). CONCLUSION: In this large
nationwide analysis, the presence of seizures in patients with SAH was associated
with higher in-hospital mortality. This finding has potentially important
implications for goals of care decision-making and prognostication, but further
study in the area is needed.
PMID- 27491070
TI - Seeking out the sweet spot in cancer therapeutics: an interview with Lewis
Cantley.
AB - Lewis C. Cantley, Director of the Sandra and Edward Meyer Cancer Center at Weill
Cornell Medicine, is a world leader in cancer and metabolic disease research. His
seminal discoveries have shed light on the regulation of ion pumps and other
transport proteins, insulin-mediated regulation of glucose metabolism and the
role of signal transduction networks in cell transformation. At Tufts University
in the 1980s, Lewis and his collaborators unveiled and characterized the
phosphoinositide 3-kinase (PI3K) signaling pathway; a discovery that
revolutionized the field of lipid signaling. In this interview, he documents his
journey from serendipitous discovery of the pathway to determining its diverse
physiological functions and role in cancer - an incredible odyssey that has laid
the groundwork for clinical trials based on PI3K inhibitors. He also discusses
the impact his early life had in spurring a thirst to understand biological
processes at the molecular level, highlights how his multiple collaborations have
helped in translating his basic discoveries to the clinic and explains why eating
a high-sugar diet can be harmful. Ongoing studies in the Cantley lab are aimed at
determining the mechanistic underpinnings of pancreatic, colorectal, ovarian and
breast cancers, particularly the role of cellular metabolic pathways. The group
has recently shown, amongst other breakthroughs, that vitamin C could provide a
promising therapy for certain hard-to-treat cancers.
PMID- 27491072
TI - A knockin mouse model for human ATP4aR703C mutation identified in familial
gastric neuroendocrine tumors recapitulates the premalignant condition of the
human disease and suggests new therapeutic strategies.
AB - By whole exome sequencing, we recently identified a missense mutation (p.R703C)
in the human ATP4a gene, which encodes the proton pump responsible for gastric
acidification. This mutation causes an aggressive familial type I gastric
neuroendocrine tumor in homozygous individuals. Affected individuals show an
early onset of the disease, characterized by gastric hypoacidity,
hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in
one case, an associated gastric adenocarcinoma. Total gastrectomy was performed
as the definitive treatment in all affected individuals. We now describe the
generation and characterization of a knockin mouse model for the ATP4a(R703C)
mutation to better understand the tumorigenesis process. Homozygous mice
recapitulated most of the phenotypical alterations that were observed in human
individuals, strongly suggesting that this mutation is the primary alteration
responsible for disease development. Homozygous mice developed premalignant
condition with severe hyperplasia, dysplasia and glandular metaplasia in the
stomach. Interestingly, gastric acidification in homozygous mice, induced by
treatment with 3% HCl acid in the drinking water, prevented (if treated from
birth) or partially reverted (if treated during adulthood) the development of
glandular metaplasia and dysplasia in the stomach and partially rescued the
abnormal biochemical parameters. We therefore suggest that, in this model,
achlorhydria contributes to tumorigenesis to a greater extent than
hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool
for studying the pathologies associated with disturbances in gastric acid
secretion.
PMID- 27491071
TI - Progressive neurologic and somatic disease in a novel mouse model of human
mucopolysaccharidosis type IIIC.
AB - Mucopolysaccharidosis type IIIC (MPSIIIC) is a severe lysosomal storage disease
caused by deficiency in activity of the transmembrane enzyme heparan-alpha
glucosaminide N-acetyltransferase (HGSNAT) that catalyses the N-acetylation of
alpha-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal
substrate accumulation in lysosomes, leading to progressive and severe
neurodegeneration, somatic pathology and early death. There is no cure for
MPSIIIC, and development of new therapies is challenging because of the
unfeasibility of cross-correction. In this study, we generated a new mouse model
of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left
LacZ expression under control of the Hgsnat promoter, allowing investigation into
sites of endogenous expression, which was particularly prominent in the CNS, but
was also detectable in peripheral organs. Signs of CNS storage pathology,
including glycosaminoglycan accumulation, lysosomal distension, lysosomal
dysfunction and neuroinflammation were detected in 2-month-old animals and
progressed with age. Glycosaminoglycan accumulation and ultrastructural changes
were also observed in most somatic organs, but lysosomal pathology seemed most
severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and
exploratory activity and shortened lifespan. Hence, this animal model
recapitulates human MPSIIIC and provides a useful tool for the study of disease
physiopathology and the development of new therapeutic approaches.
PMID- 27491073
TI - A mouse model for ulcerative colitis based on NOD-scid IL2R gammanull mice
reconstituted with peripheral blood mononuclear cells from affected individuals.
AB - Animal models reflective of ulcerative colitis (UC) remain a major challenge, and
yet are crucial to understand mechanisms underlying the onset of disease and
inflammatory characteristics of relapses and remission. Mouse models in which
colitis-like symptoms are induced through challenge with toxins such as
oxazolone, dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzenesulfonic acid
(TNBS) have been instrumental in understanding the inflammatory processes of UC.
However, these neither reflect the heterogeneous symptoms observed in the UC
affected population nor can they be used to test the efficacy of inhibitors
developed against human targets where high sequence and structural similarity of
the respective ligands is lacking. In an attempt to overcome these problems, we
have developed a mouse model that relies on NOD-scid IL2R gamma(null) mice
reconstituted with peripheral blood mononuclear cells derived from UC-affected
individuals. Upon challenge with ethanol, mice developed colitis-like symptoms
and changes in the colon architecture, characterized by influx of inflammatory
cells, edema, crypt loss, crypt abscesses and epithelial hyperplasia, as
previously observed in immune-competent mice. TARC, TGFbeta1 and HGF expression
increased in distal parts of the colon. Analysis of human leucocytes isolated
from mouse spleen revealed an increase in frequencies of CD1a+, CD64+, CD163+ and
TSLPR+ CD14+ monocytes, and antigen-experienced CD44+ CD4+ and CD8+ T-cells in
response to ethanol. Analysis of human leucocytes from the colon of challenged
mice identified CD14+ monocytes and CD11b+ monocytes as the predominant
populations. Quantitative real-time PCR (RT-PCR) analysis from distal parts of
the colon indicated that IFNgamma might be one of the cytokines driving
inflammation. Treatment with infliximab ameliorated symptoms and pathological
manifestations, whereas pitrakinra had no therapeutic benefit. Thus, this model
is partially reflective of the human disease and might help to increase the
translation of animal and clinical studies.
PMID- 27491074
TI - Development of a subset of forelimb muscles and their attachment sites requires
the ulnar-mammary syndrome gene Tbx3.
AB - In the vertebrate limb over 40 muscles are arranged in a precise pattern of
attachment via muscle connective tissue and tendon to bone and provide an
extensive range of motion. How the development of somite-derived muscle is
coordinated with the development of lateral plate-derived muscle connective
tissue, tendon and bone to assemble a functional limb musculoskeletal system is a
long-standing question. Mutations in the T-box transcription factor, TBX3, have
previously been identified as the genetic cause of ulnar-mammary syndrome (UMS),
characterized by distinctive defects in posterior forelimb bones. Using
conditional mutagenesis in mice, we now show that TBX3 has a broader role in limb
musculoskeletal development. TBX3 is not only required for development of
posterior forelimb bones (ulna and digits 4 and 5), but also for a subset of
posterior muscles (lateral triceps and brachialis) and their bone eminence
attachment sites. TBX3 specification of origin and insertion sites appears to be
tightly linked with whether these particular muscles develop and may represent a
newly discovered mechanism for specification of anatomical muscles. Re
examination of an individual with UMS reveals similar previously unrecognized
muscle and bone eminence defects and indicates a conserved role for TBX3 in
regulating musculoskeletal development.
PMID- 27491075
TI - A mouse model for fucosidosis recapitulates storage pathology and neurological
features of the milder form of the human disease.
AB - Fucosidosis is a rare lysosomal storage disorder caused by the inherited
deficiency of the lysosomal hydrolase alpha-L-fucosidase, which leads to an
impaired degradation of fucosylated glycoconjugates. Here, we report the
generation of a fucosidosis mouse model, in which the gene for lysosomal alpha-L
fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice
completely lack alpha-L-fucosidase activity in all tested organs leading to
highly elevated amounts of the core-fucosylated glycoasparagine Fuc(alpha1,6)
GlcNAc(beta1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines,
which all were also partially excreted in urine. Lysosomal storage pathology was
observed in many visceral organs, such as in the liver, kidney, spleen and
bladder, as well as in the central nervous system (CNS). On the cellular level,
storage was characterized by membrane-limited cytoplasmic vacuoles primarily
containing water-soluble storage material. In the CNS, cellular alterations
included enlargement of the lysosomal compartment in various cell types,
accumulation of secondary storage material and neuroinflammation, as well as a
progressive loss of Purkinje cells combined with astrogliosis leading to
psychomotor and memory deficits. Our results demonstrate that this new
fucosidosis mouse model resembles the human disease and thus will help to unravel
underlying pathological processes. Moreover, this model could be utilized to
establish diagnostic and therapeutic strategies for fucosidosis.
PMID- 27491076
TI - Autocrine IL-10 activation of the STAT3 pathway is required for pathological
macrophage differentiation in polycystic kidney disease.
AB - Polycystic kidney disease (PKD) is characterized by slow expansion of fluid
filled cysts derived from tubules within the kidney. Cystic expansion results in
injury to surrounding parenchyma and leads to inflammation, scarring and
ultimately loss of renal function. Macrophages are a key element in this process,
promoting cyst epithelial cell proliferation, cyst expansion and disease
progression. Previously, we have shown that the microenvironment established by
cystic epithelial cells can 'program' macrophages, inducing M2-like macrophage
polarization that is characterized by expression of markers that include Arg1 and
Il10 Here, we functionally characterize these macrophages, demonstrating that
their differentiation enhances their ability to promote cyst cell proliferation.
This observation indicates a model of reciprocal pathological interactions
between cysts and the innate immune system: cyst epithelial cells promote
macrophage polarization to a phenotype that, in turn, is especially efficient in
promoting cyst cell proliferation and cyst growth. To better understand the
genesis of this macrophage phenotype, we examined the role of IL-10, a regulatory
cytokine shown to be important for macrophage-stimulated tissue repair in other
settings. Herein, we show that the acquisition of the pathological macrophage
phenotype requires IL-10 secretion by the macrophages. Further, we demonstrate a
requirement for IL-10-dependent autocrine activation of the STAT3 pathway. These
data suggest that the IL-10 pathway in macrophages plays an essential role in the
pathological relationship between cysts and the innate immune system in PKD, and
thus could be a potential therapeutic target.
PMID- 27491077
TI - A high-fat jelly diet restores bioenergetic balance and extends lifespan in the
presence of motor dysfunction and lumbar spinal cord motor neuron loss in TDP
43A315T mutant C57BL6/J mice.
AB - Transgenic transactivation response DNA-binding protein 43 (TDP-43) mice
expressing the A315T mutation under control of the murine prion promoter
progressively develop motor function deficits and are considered a new model for
the study of amyotrophic lateral sclerosis (ALS); however, premature sudden death
resulting from intestinal obstruction halts disease phenotype progression in 100%
of C57BL6/J congenic TDP-43(A315T) mice. Similar to our recent results in
SOD1(G93A) mice, TDP-43(A315T) mice fed a standard pellet diet showed increased
5' adenosine monophosphate-activated protein kinase (AMPK) activation at
postnatal day (P)80, indicating elevated energetic stress during disease
progression. We therefore investigated the effects of a high-fat jelly diet on
bioenergetic status and lifespan in TDP-43(A315T) mice. In contrast to standard
pellet-fed mice, mice fed high-fat jelly showed no difference in AMPK activation
up to P120 and decreased phosphorylation of acetly-CoA carboxylase (ACC) at early
stage time points. Exposure to a high-fat jelly diet prevented sudden death and
extended survival, allowing development of a motor neuron disease phenotype with
significantly decreased body weight from P80 onward that was characterised by
deficits in Rotarod abilities and stride length measurements. Development of this
phenotype was associated with a significant motor neuron loss as assessed by
Nissl staining in the lumbar spinal cord. Our work suggests that a high-fat jelly
diet improves the pre-clinical utility of the TDP-43(A315T) model by extending
lifespan and allowing the motor neuron disease phenotype to progress, and
indicates the potential benefit of this diet in TDP-43-associated ALS.
PMID- 27491079
TI - Update on Vaccine-Derived Polioviruses - Worldwide, January 2015-May 2016.
AB - In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide
(1). One of the main tools used in polio eradication efforts has been the live,
attenuated, oral poliovirus vaccine (OPV) (2), an inexpensive vaccine easily
administered by trained volunteers. OPV might require several doses to induce
immunity, but provides long-term protection against paralytic disease. Through
effective use of OPV, the Global Polio Eradication Initiative (GPEI) has brought
wild polioviruses to the threshold of eradication (1). However, OPV use,
particularly in areas with low routine vaccination coverage, is associated with
the emergence of genetically divergent vaccine-derived polioviruses (VDPVs) whose
genetic drift from the parental OPV strains indicates prolonged replication or
circulation (3). VDPVs can emerge among immunologically normal vaccine recipients
and their contacts as well as among persons with primary immunodeficiencies
(PIDs). Immunodeficiency-associated VDPVs (iVDPVs) can replicate for years in
some persons with PIDs. In addition, circulating vaccine-derived polioviruses
(cVDPVs) (3) can emerge in areas with low OPV coverage and can cause outbreaks of
paralytic polio. This report updates previous summaries regarding VDPVs (4).
PMID- 27491078
TI - A human pluripotent stem cell model of catecholaminergic polymorphic ventricular
tachycardia recapitulates patient-specific drug responses.
AB - Although beta-blockers can be used to eliminate stress-induced ventricular
arrhythmias in patients with catecholaminergic polymorphic ventricular
tachycardia (CPVT), this treatment is unsuccessful in ~25% of cases. Induced
pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from these
patients have potential for use in investigating the phenomenon, but it remains
unknown whether they can recapitulate patient-specific drug responses to beta
blockers. This study assessed whether the inadequacy of beta-blocker therapy in
an individual can be observed in vitro using patient-derived CPVT iPSC-CMs. An
individual with CPVT harboring a novel mutation in the type 2 cardiac ryanodine
receptor (RyR2) was identified whose persistent ventricular arrhythmias during
beta-blockade with nadolol were abolished during flecainide treatment. iPSC-CMs
generated from this patient and two control individuals expressed comparable
levels of excitation-contraction genes, but assessment of the sarcoplasmic
reticulum Ca(2+) leak and load relationship revealed intracellular Ca(2+)
homeostasis was altered in the CPVT iPSC-CMs. beta-adrenergic stimulation
potentiated spontaneous Ca(2+) waves and unduly frequent, large and prolonged
Ca(2+) sparks in CPVT compared with control iPSC-CMs, validating the disease
phenotype. Pursuant to the patient's in vivo responses, nadolol treatment during
beta-adrenergic stimulation achieved negligible reduction of Ca(2+) wave
frequency and failed to rescue Ca(2+) spark defects in CPVT iPSC-CMs. In
contrast, flecainide reduced both frequency and amplitude of Ca(2+) waves and
restored the frequency, width and duration of Ca(2+) sparks to baseline levels.
By recapitulating the improved response of an individual with CPVT to flecainide
compared with beta-blocker therapy in vitro, these data provide new evidence that
iPSC-CMs can capture basic components of patient-specific drug responses.
PMID- 27491080
TI - Assessment of periodontal mechano-nociceptive function in healthy Chinese
individuals.
AB - OBJECTIVE: Few clinical techniques are available for the description of mechano
nociceptive function in human periodontal tissues. The objective of this study
was to test a new technique for assessment of periodontal mechano-nociceptive
function by direct application of controlled forces to the teeth and quantify
site, side and gender differences in healthy individuals. DESIGN: Twenty healthy
young adults (ten males and ten females) participated. A handheld pressure
algometer was used to assess pressure pain threshold (PPT) on the maxillary and
mandibular central incisors, canines and first premolars on the left and the
right side from two directions: lateral and vertical. Statistical analysis was
performed using analyses of variance (ANOVA) with repeated measures to compare
data. RESULTS: There were significant gender differences of PPT for both lateral
(Plateral=0.007) and vertical (Pvertical=0.001) directions with lower thresholds
in females (higher sensitivity) than in males. A significant site effect
(Plateral=0.002, Pvertical<0.001) was observed with less sensitivity at the first
premolar compared to the anterior teeth. No significant right-to-left side
differences (P=0.082) were found for the PPTs. There were significant PPT
differences between maxillary and mandibular teeth (Plateral=0.020,
Pvertical=0.041,) and significant differences between lateral and vertical
direction (P<0.001). CONCLUSION: The novel application of PPTs directly to the
teeth indicated an adequate and practical method with potential value for
clinical assessment of painful conditions affecting the periodontal ligament.
PMID- 27491081
TI - Characterization of a novel mutation in PAX9 gene in a family with non-syndromic
dental agenesis.
AB - BACKGROUND: Dental agenesis is the most common developmental anomaly in man and
may present either as an isolated trait or as part of a syndrome, such as
ectodermal dysplasia. Until now, the underlying molecular pathogenic mechanisms
responsible for dental agenesis are still largely unknown. Several genetic and
molecular studies have demonstrated that at least 300 genes are involved in tooth
formation and development, coding for specific transcriptional factors, receptors
or growth factors that are expressed at specific developmental stages. Dental
agenesis in this respect is believed to result from altered expression of one or
more of these factors during initiation and early morphogenesis of the tooth
germ, and the first actors identified were MSX1 and PAX9. DESIGN: In this study,
we focalized on a Tunisian family with a non-syndromic autosomal dominant form of
tooth agenesis. In order to screen for the eventual genetic cause of dental
agenesis in this family we sequenced 4 genes; PAX9, WNT10A, MSX1 and AXIN2 using
Sanger sequencing. RESULTS: Direct Screening analysis of PAX9 gene, revealed a
novel mutation p.Asp200Serfs*13. It consists of a duplication of 5 basepairs
leading to a codon stop 13 position downstream. This novel mutation was found in
all affected family members. CONCLUSIONS: In this report, we present the first
genetic study of a Tunisian family with a non-syndromic autosomal dominant form
of tooth agenesis, in which we identified in PAX9 gene a novel mutation. It most
likely results in nonsense mediated RNA decay and haploinsifficiency that reduce
the transactivation capacity of PAX9.
PMID- 27491083
TI - Cancer risk in siblings of children with congenital malformations.
AB - PURPOSE: Cancer and birth defects cluster in families more often than expected by
chance, but the reasons are neither well known nor well studied. METHODS: From
singletons born alive in Denmark between 1 January 1977 and 31 December 2007, we
identified children who had no congenital malformations but had a full or half
sibling with a congenital malformation (CM) diagnosed in the first year of life;
this constituted the exposed group, while children whose siblings had no such
condition constituted a reference group. We estimated cancer risks for children
who had a full sibling or a half sibling with a CM using a Cox proportional
hazards regression model. To control for confounding related to change of family
structure, we estimated cancer risks for children from core families and children
from broken families separately. Children were followed from birth up to 30 years
of age (median follow-up 13.6 years). We obtained information on CMs and cancer
from the Danish National Hospital Register and the Danish Cancer Registry.
RESULTS: We identified 991,454 (78%) children from core families with 53,995
children who had a full sibling with a CM and 277,773 (22%) children from broken
families with 7200 children who had a full sibling with a CM and 6194 children
who had a half sibling with a CM. Children who had a full sibling with a CM from
both core and broken families showed, in general, no increased cancer risk
compared with children whose siblings had no CM, except in the case of children
who had a full sibling with a CM in the nervous system (HR=2.61, 95%CI:1.60-4.27)
or in the eye, ear, face, or neck (HR=2.47, 95%CI: 1.46-4.18). Children who had a
half sibling with a CM seemed to have a higher cancer risk in early adulthood
(HR=1.87, 95%CI: 0.98-3.56). CONCLUSIONS: Children who had a full sibling with a
CM had no increased risk of cancer except for those who had a full sibling with a
CM in the nervous system or in the eye, ear, face or neck. Children with a half
sibling with a CM tended to have an increased cancer risk in early adulthood,
perhaps a result of chance. This study should be replicated using other data
sources.
PMID- 27491082
TI - Histologic characterization of regenerated tissues after pulp revascularization
of immature dog teeth with apical periodontitis using tri-antibiotic paste and
platelet-rich plasma.
AB - INTRODUCTION: This study evaluates histologically the efficacy of 4
revascularization protocols in necrotic-infected immature dog teeth with apical
periodontitis (AP). METHODS: Forty double-rooted immature premolar teeth from 4
female Beagle dogs aged 5 months were used. Four teeth were left untouched as
negative controls; the other 36 teeth were infected to develop pulp necrosis and
AP. Four teeth were left untreated and assigned to the positive control group.
The last 28 teeth were randomly assigned into four experimental groups of 8
teeth, each one treated with a different treatment protocol: A1, sodium
hypochlorite (SH)+blood clot (BC); A2, SH+platelet-rich plasma (PRP); B1,
SH+modified tri-antibiotic paste (mTAP)+BC; B2, SH+mTAP+PRP. The animals were
sacrificed, histologic sections were prepared and three parameters were assessed:
(1) presence or absence of new hard tissue on the internal root dentinal walls,
(2) presence or absence of continued apical closure, and (3) presence or absence
of vital tissue within the canal space. RESULTS: Significant differences (p<0.05)
between the four experimental groups were evident in the percentage of teeth
showing histological apical closure (34.5%) and vital tissue within the canal
space (68.8%). Group B2 showed the maximal improvement in the three variables
assessed (p<0.05). Group A1 showed the minimum percentages in the three
parameters assessed (p<0.05). CONCLUSIONS: These results suggest that an
intracanal dressing of mTAP, and the use of PRP as scaffold, improves the success
rate of the revascularization procedure.
PMID- 27491086
TI - Reply.
PMID- 27491084
TI - Model systems of protein-misfolding diseases reveal chaperone modifiers of
proteotoxicity.
AB - Chaperones and co-chaperones enable protein folding and degradation, safeguarding
the proteome against proteotoxic stress. Chaperones display dynamic responses to
exogenous and endogenous stressors and thus constitute a key component of the
proteostasis network (PN), an intricately regulated network of quality control
and repair pathways that cooperate to maintain cellular proteostasis. It has been
hypothesized that aging leads to chronic stress on the proteome and that this
could underlie many age-associated diseases such as neurodegeneration.
Understanding the dynamics of chaperone function during aging and disease-related
proteotoxic stress could reveal specific chaperone systems that fail to respond
to protein misfolding. Through the use of suppressor and enhancer screens, key
chaperones crucial for proteostasis maintenance have been identified in model
organisms that express misfolded disease-related proteins. This review provides a
literature-based analysis of these genetic studies and highlights prominent
chaperone modifiers of proteotoxicity, which include the HSP70-HSP40 machine and
small HSPs. Taken together, these studies in model systems can inform strategies
for therapeutic regulation of chaperone functionality, to manage aging-related
proteotoxic stress and to delay the onset of neurodegenerative diseases.
PMID- 27491087
TI - [The beginnings of kidney transplantation in Debrecen, Hungary].
PMID- 27491088
TI - Change: the Forerunner of Progress.
PMID- 27491090
TI - A Valuable Year.
PMID- 27491089
TI - Real-Time Assessment of Osseous Tissue Changes After Guided Bone Regeneration.
PMID- 27491085
TI - Loss of vhl in the zebrafish pronephros recapitulates early stages of human clear
cell renal cell carcinoma.
AB - Patients with von Hippel-Lindau (VHL) disease harbor a germline mutation in the
VHL gene leading to the development of several tumor types including clear cell
renal cell carcinoma (ccRCC). In addition, the VHL gene is inactivated in over
90% of sporadic ccRCC cases. 'Clear cell' tumors contain large, proliferating
cells with 'clear cytoplasm', and a reduced number of cilia. VHL inactivation
leads to the stabilization of hypoxia inducible factors 1a and 2a [HIF1a and
HIF2a (HIF2a is also known as EPAS1)] with consequent up-regulation of specific
target genes involved in cell proliferation, angiogenesis and erythropoiesis. A
zebrafish model with a homozygous inactivation in the VHL gene (vhl(-/-))
recapitulates several aspects of the human disease, including development of
highly vascular lesions in the brain and the retina and erythrocytosis. Here, we
characterize for the first time the epithelial abnormalities present in the
kidney of the vhl(-/-) zebrafish larvae as a first step in building a model of
ccRCC in zebrafish. Our data show that the vhl(-/-) zebrafish kidney is
characterized by an increased tubule diameter, disorganized cilia, the dramatic
formation of cytoplasmic lipid vesicles, glycogen accumulation, aberrant cell
proliferation and abnormal apoptosis. This phenotype of the vhl(-/-) pronephros
is reminiscent of clear cell histology, indicating that the vhl(-/-) mutant
zebrafish might serve as a model of early stage RCC. Treatment of vhl(-/-)
zebrafish embryos with a small-molecule HIF2a inhibitor rescued the pronephric
abnormalities, underscoring the value of the zebrafish model in drug discovery
for treatment of VHL disease and ccRCC.
PMID- 27491091
TI - Home field advantage...
PMID- 27491092
TI - Troubleshooting Tips.
PMID- 27491093
TI - Confronting a crisis: An open letter to America's physicians on the opioid
epidemic.
PMID- 27491094
TI - AARP Now Advocates for APRNs, but Does it Still Advocate for Seniors?
PMID- 27491095
TI - Immunization Awareness Month.
PMID- 27491097
TI - Best Friend...
PMID- 27491098
TI - The Undescended Testicles of West Virginia: A Single Center Experience.
AB - OBJECTIVE: To determine the age of pediatric patients who underwent surgical
intervention for undescended testicles (UDT) at our institution. METHODS: We
retrospectively reviewed all pediatric patients who underwent orchiopexy and/or
diagnostic laparoscopy for undescended or non-palpable testicles with our
pediatric urologist from January 2013-March 2014. Patients were separated into
those undergoing surgical intervention at 6-12 months, 13-24 months, 25-48
months, and >48 months of age. RESULTS: 70 patients underwent surgical
intervention. Only 15 patients (21.4%) underwent surgical intervention within the
recommended time period of 6-12 months. Orchiopexy was performed on 21 patients
(30.0%) from 13-24 months, 12 patients (17.1%) from 25-48 months, and 22 patients
(31.5%) after 48 months of age. CONCLUSIONS: Current American Urologic
Association (AUA) recommendations advocate orchiopexy between 6-12 months of age.
Improved parent and primary care education and access to pediatric urological
evaluation of UDT will hopefully improve the timeliness of intervention within
our state.
PMID- 27491099
TI - Pre-operative Identification and Surgical Management of the Appendiceal Mucocele:
A Case Report.
AB - An appendiceal mucocele (AM) is an uncommon differential in the patient being
evaluated for acute appendicitis. Although often asymptomatic, AMs can clinically
mimic acute appendicitis, and preoperative distinction between these processes
facilitates optimal management. We report the case of a 60-year-old male with an
AM presenting with nausea and periumbilical pain radiating to the right lower
quadrant. Literature relevant to the diagnosis and treatment of AMs is reviewed,
with emphasis on diagnosis through radiographic imaging and surgical management.
Abdominal CT scan or ultrasound are useful in identifying AMs preoperatively. A
decision to perform a right hemicolectomy should be influenced by the criteria
reported by Gonzalez-Moreno. The safety of the laparoscopic resection relative to
an open appendectomy is debated.
PMID- 27491100
TI - Bone Mineral Density and Vitamin D Level Compared to Lifestyle in Resident
Physicians.
AB - Due to the demands of resident education and long periods of time spent indoors,
resident physicians may have poorer bone quality than would be expected. Forty
four resident physicians underwent dual-energy X-ray absorptiometry (DEXA) and 25
hydroxyvitamin D level testing at our institution. Results were correlated with a
survey of self-reported duty hours, physical activity, and sun exposure. The
average 25-hydroxyvitamin D level for all participants was 29 ng/dL, which fell
into the insufficient range, and 31.5% of all participants were in the deficient
range, with a 25-hydroxyvitamin D level < 20 ng/ dL. For the 40 subjects who
underwent DEXA, 17 were found to be osteopenic and three were found to be
osteoporotic. Greater awareness of bone health, with routine use of vitamin D
supplementation and increased time spent outdoors during peak sunlight hours, may
be indicated in this cohort.
PMID- 27491101
TI - Inconspicuous Presentation of Metastatic Neuroblastoma.
AB - Neuroblastoma is a malignant tumor arising from nerve tissue that accounts for
approximately 15 percent of pediatric cancer fatalities. Primary tumors most
commonly arise in sympathetic nervous tissue of the abdomen and metastasize to
the bone marrow, liver, and lymph nodes. This case report depicts a 3-year-old
girl who presented with a recurring fever, runny nose, and a positive test for
rhinovirus suggesting a simple case of the common cold. Further investigation,
however, revealed stage 4 neuroblastoma. This patient experience emphasizes the
importance of having a high level of suspicion to rule out more serious
underlying pathology in a seemingly unremarkable patient presentation.
PMID- 27491102
TI - Implementing Universal Pulse Oximetry Screening in West Virginia: Findings from
Year One.
AB - BACKGROUND: In March 2012 the West Virginia legislature passed a law that
mandates birth hospitals to perform pulse oximetry screening for all well-babies
in the newborn nursery to improve the detection of critical congenital heart
disease (CCHD). CCHD screening data collection began on September 1, 2012 at all
28 birthing hospitals. The purpose of this study was to review the first year of
pulse oximetry screening outcomes and identify barriers to implementation and
solutions to improve tracking and policy. METHODS: All WV birth hospitals were
provided with the U.S. Department of Health and Human Services recommendations
for CCHD screening, and the Center for Disease Control's recommended screening
algorithm for review and reference. 20,115 infants were entered into the Birth
Score database between September 1, 2012 and August 31, 2013. 19,283 (91%)
infants were screened for CCHD. RESULTS: 17,101 (88.5%) infants passed, 19
infants failed, and 2,163 (11.2%) infants had missing data for the screening. 832
infants were not screened due to being admitted to the neonatal intensive care
unit for reasons unknown. 17 of the 19 infants who failed the screening had a
transthoracic echo report available for review. Of those 17 infants reviewed,
seven were diagnosed with CCHD. CONCLUSIONS: 85% of the infants born in WV who
received a Birth Score during the year reviewed were screened for CCHD. Given
that the goal is to have 100% compliance with the pulse oximetry screening,
additional investigations into factors affecting compliance may be necessary.
PMID- 27491103
TI - Lyme Disease in West Virginia: An Assessment of Distribution and Clinicians'
Knowledge of Disease and Surveillance.
AB - Lyme disease case misclassification, a top public health concern, may be
attributed to the current disconnect between clinical diagnosis and surveillance.
This study examines Lyme disease distribution in West Virginia (WV) and
determines clinicians' knowledge of both disease and surveillance. Lyme disease
surveillance data for 2013 were obtained from the WV Bureau for Public Health. A
validated survey, distributed to clinicians at an academic medical center,
assessed clinicians' knowledge of disease diagnosis and surveillance. There were
297 adult Lyme disease cases of which 83 were confirmed. Clinician survey
responses resulted in a correct response rate of 70% for Lyme disease knowledge
questions. Fewer than half of all clinicians were aware of the surveillance
criteria for confirming Lyme disease cases. Neither medical specialty nor
previous treatment of patients with Lyme disease were significantly associated
with clinicians' knowledge of the disease. Clinicians in WV are familiar with
symptoms and clinical management of Lyme disease. However, they are less
knowledgeable about diagnosis and public health surveillance comprising reporting
and confirming cases of the disease. Clinicians and public health authorities
should collaborate more closely to promote education and awareness as a key step
to successfully reducing the burden of Lymne disease.
PMID- 27491104
TI - DISASTER PREPAREDNESS: ARE YOU READY?
PMID- 27491105
TI - BACK TO SCHOOL.
PMID- 27491106
TI - Monogenic Diabetes: Not Your "Typical" Diabetes.
PMID- 27491107
TI - DINNER TO YOUR DOOR.
PMID- 27491108
TI - SUPERMARKET SMARTS. BEANS, PEAS and LENTILS.
PMID- 27491109
TI - IN THE KITCHEN WITH THE DIABETIC CHEF. CHRIS SMITH SHARES HIS PERSONAL JOURNEY
WITH DIABETES AND HIS APPROACH TO HEALTHY COOKING.
PMID- 27491111
TI - Take 5. Posture and Core Strength.
PMID- 27491110
TI - Summer portion control: from beach to barbecue.
PMID- 27491113
TI - WHAT PEOPLE LIVING WITH HIV SAY ABOUT NOT COMING IN FOR HEALTH CARE.
PMID- 27491112
TI - Getting to Know You. Sierra Sandison.
PMID- 27491114
TI - A SUCCESS STORY IN HIV LINKAGE TO CARE AND RETENTION.
PMID- 27491115
TI - MAGICAL THINKING IN HIV: MUCH MORE THAN DENIAL.
PMID- 27491116
TI - TAKING THE HILL.
PMID- 27491118
TI - YOU'VE LOST THAT GUTSY FEELING, WHOA, THAT GUTSY FEELING.
PMID- 27491117
TI - HEPATITIS C AT CROI.
PMID- 27491119
TI - RECONNECTING WITH HER COMMUNITY. FEELING FREE WITH THE RIDE FOR AIDS CHICAGO.
PMID- 27491120
TI - STAYING IN THE GAME.
PMID- 27491122
TI - NOT SO FAST.
PMID- 27491121
TI - ALL SYSTEMS GO.
PMID- 27491123
TI - JESSE PEEL IS AGING SWIMMINGLY.
PMID- 27491124
TI - HELL IN A HOT FLASH?
PMID- 27491126
TI - FOR ME AND MY BROTHER.
PMID- 27491125
TI - CAN OLDER PEOPLE GET SOME... SATISFACTION?
PMID- 27491127
TI - ALONE TIME.
PMID- 27491128
TI - TRANSFORMING LIVES.
PMID- 27491129
TI - PLANNING AHEAD.
PMID- 27491130
TI - Bridgepoint Active Healthcare: Stantec Architecture, KPMB Architects, HDR
Architecture, Diamond Schmitt Architects, Toronto.
PMID- 27491131
TI - Baby Its Cold Outside.
PMID- 27491133
TI - An Interview with the President-Elect: Dr. Barsley.
PMID- 27491132
TI - Does Hiring an Advertising Agency Cost My Dental Practice Money?
PMID- 27491134
TI - When the price of the blood-pressure drug Nitropress leaped from $215 to $881
last year, an increase of 310%, it triggered public outrage: What's behind the
gouging?.
PMID- 27491136
TI - BIG INNOVATION IN SMALL PLACES.
PMID- 27491135
TI - New U.S. nutrition labels will emphasize calories and sugar.
PMID- 27491137
TI - INTO THE LIGHT.
PMID- 27491138
TI - Integrated Disability Management: Implementing a Customized Whole-Person
Approach.
AB - This article describes how incorporating integrated disability management can
address business challenges. It includes case studies featuring organizations
that used a "whole-person approach" to result in (1) greater and more effective
communication and reporting, (2) more satisfied and productive employees and (3)
cost savings through quicker return to work when legally and medically
appropriate, all in alignment with the particular needs of a given firm. One size
most definitely does not fit all.
PMID- 27491139
TI - A Generation With Income to Protect.
AB - From an employee benefits perspective, generational differences undoubtedly play
a big role in not only how to communicate with employees about their benefits but
what benefits to offer. Yet while there's been a lot of talk about how to reach
other generations, information about connecting with Generation X is harder to
come by. This article discusses the state of Generation X's unique income
protection and financial concerns. The author shows how offering income
protection to Generation Xers not only helps them deal with today's expenses and
prepare for the future but can also help employers meet business objectives such
as attracting and retaining top talent.
PMID- 27491140
TI - Don't Let Disability Derail Long-Term Financial Security: Enhancing Retirement
Security in a DC World.
AB - Long-term disability (LTD) protection, such as a defined contribution (DC)
disability supplement, is critical for good long-term security in a DC
environment. For those with a strong LTD program already in place, this challenge
can be addressed by providing a DC disability benefit that replaces DC
contributions during periods of LTD. If there is no LTD program, that is needed
first. Appropriate disability coverage is vital if the DC system truly is to
deliver long-term retirement security. This article discusses issues in achieving
such coverage and provides ideas to help in developing programs. Few such
programs exist today, but it is hoped that this article will encourage more
employers to adopt them.
PMID- 27491141
TI - Engagement and Empowerment Through Self-Service.
AB - Self-service tools represent the next frontier for leave and disability. This
article discusses several critical com- ponents of a successful leave and
disability self-service tool. If given the proper investment and thoughtfully
designed, self-service tools have the potential to augment an organization's
existing interaction channels, im- proving the employee experience while
delivering efficiencies for an administrative model. In an operating en-
vironment in which cost savings sometimes are at the expense of employee
experience, such a win-win solution should not be taken lightly and, more
importantly, should not be missed.
PMID- 27491142
TI - Pharmacies Denied Injunction Against Pharmacy Benefit Manager. Grasso
Enterprises, LLC v. Express Scripts, Inc., 809 F.3d 1033 (8th Cir. Jan. 11,2016).
PMID- 27491143
TI - [PROBLEM OF ENDOMETRIUM HYPERPLASTIC PROCESSES IN REPRODUCTIVE AGE WOMEN].
AB - The article presents the risk factors of endometrium hyperplastic processes (EHP)
in reproduc- tive age women. It is shown that EHP occur in response to hormonal
homeostasis violations of the target tissues. It is established that the
biologically active substances, which are closely related to immune mechanisms of
the reproductive system functioning take place in regulatory mechanisms of cell
growth and differentiation of endometrium.
PMID- 27491144
TI - [ERRORS IN DIAGNOSIS AND TREATMENT OF IMMUNODEPENDENT PATHOLOGY (ORIGINAL
CONCEPT)].
AB - Based on many years of experience in 2009, we developed the original concept of a
mixed approach to the treatment of infectious diseases in patients. During 2.5
years(from 2013 to June 2015) to have applied for consultative-diagnostic help of
3965 patients who had not verified the primary diagnosis. The basic principle of
verification of the pathology of the removal of various causes immunosuppression.
Based on our extensive, research and observation was often found in patients
ascaridosis (55%) and giardiasis (65%), as a possible cause of immunosuppression.
In 13% of patients was found the mucosal candidiasis. Among frequently and
chronically ill persons we identified the active forms of Epstein-Barr virus
(quantitative polymerase chain reaction in saliva) in 40%. The criterion for
assessing performance immunogram was a decrease of two sigmal deviation from the
lower age limit. In the study of neutrophil myeloperoxidase content observed
decline (< 60%) in 99 (9.7%) of 1015 patients, indicating a fairly common cause
of long-term permit infection in the tissues and persistence C. albicans. In the
study of lymphocyte subpopulations often demonstrated reduction in the number of
natural killer cells (26.7% of subjects), which shows a decline of one of the
most important factors of congenital immunity. Among the humoral immune disorders
often noted the decrease of total IgG (2.4%) and its subclass IgG1 (22.1%),
indicating a significant diagnostic value determination of IgG subclasses it even
with normal serum total. Thus, approximately 76% of patients often suffer set of
a decrease immunity. Patients developed with mixed infections caused by various
bacterial, fungal, viral and protozoan agents and worms. Immunological study of
patients should be redynamics after eliminating the causes immunosuppression and
sanitation foci of infection. Only multi-level examination of the patient will
determine the final diagnosis and adequate treatment.
PMID- 27491145
TI - [REGRESSION OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH ESSENTIAL
HYPERTENSION AND LONG-TERM THERAPY WITH LOSARTAN].
AB - In 106 patients with essential hypertension stage II losartan effectively lowers
systolic and diastolic blood pressure during the day, thus contributing to the
normalization of the circadian blood pressure profile in patients with initial
breach, and does not affect the normal circadian rhythm. Long losartan promotes
regression remodeling processes of cardiac muscle and reduce preload and
afterload.
PMID- 27491147
TI - [EFFICIENCY OF CONCOMITANT USE OF POLICOSANOL AND ROSUVASTATIN IN PATIENTS WITH
STABLE CORONARY ARTERY DISEASE AND MODERATE HEPATIC DYSFUNCTION].
AB - The article presents the results for the study of lipid correction capacity and
safety of concomitant use of policosanol and rosuvastatin compared with
rosuvastatin monotherapy in patients with stable coronary artery disease and
moderate hepatic dysfunction. Fifty-seven subjects aged 37 to 72 years (mean age
54.4 years +/- 6.5 years) have been enrolled into the study with the following
inclusion criteria: therapy with statins for more than 8 weeks, failure to
achieve target LDL cholesterol levels and moderately elevated liver enzymes. The
following laboratory tests were performed at baseline and after 12 weeks of
follow-up: blood lipid profile (total cholesterol (TC), low density lipoprotein
cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), high
density lipoprotein cholesterol (HDL-C) and triglycerides (TG), lipid
peroxidation (ma- Ionic dialdehyde (MDA), glycosylated hemoglobin HbAlc (%) and
liver function tests (gamma-glutamyl transpeptidase-gamma-GTP) and alanine
aminotransferase (ALT). Concomitant use of policosanol with rosuvastatin was
superior to rosuvastatin monotherapy in terms of reduction of pro-aterogenicity
of lipid metabolism by decreasing serum TC, LDL-C and TG, increasing serum HDL-C
and decreasing the pro-oxidative activity (MDA) with simultaneous substantial
improvement of hepatic function. Concomitant use of policosanol at the dose of 20
mg/day and rosuvastatin at 10-20 mg/day was favorably tolerated. None of the
subjects had any discontinuations of therapy due to adverse events.
PMID- 27491146
TI - [EFFICACY OF STANDARD TWO-YEAR COMPREHENSIVE THERAPY TO ACHIEVE TARGET BLOOD
PRESSURE AND REGRESSION DEGREES OF REMODELING OF THE LEFT VENTRICULAR HYPERTROPHY
IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION WITH COMORBID HYPERTENSION].
AB - The study involved 23 men after acute myocardial infarction (AMI) with comorbid
arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent
myocardial infarction was determined in 38.4%, cardiac failure I-III functional
classes--100% of the cases. All patients underwent clinical examination,
electrocardiography and echocardiography, blood lipid profile. Standard
comprehensive treatment for two years included an perindopril 5-10 mg/day, beta
blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and
aspirin--75 mg/day. The patients after treatment was determined by a gradual
increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left
ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric
-in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to
treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%,
indicating the development of cardiac remodeling. After the treatment was
determined by marked reduction III (large) degree and transfer it in the II
(moderate) and I (small) degree of left ventricular hypertrophy due to more or
less pronounced changes remodeling left ventricular. The obtained data allow a
more detailed and adequately assess the structural and functional outcome
variables and determine the regression of myocardial hypertrophy in the
background to achieve target blood pressure, which is important in practical
cardiology.
PMID- 27491148
TI - [OVERWEIGHT CAUSES A DECREASE STOCKS CARDIOVASCULAR SYSTEM].
AB - Examined 117 students of the National Pedagogical Dragomanov University to assess
body mass index and indicators of the functional state of the cardiovascular
system. Was established that regulatory mechanisms in students with overweight
and underweight are in a state of tension and functionalities of the
cardiovascular system are reduced under normal conditions of learning.
PMID- 27491150
TI - [PATOGENETIC VALUE OF VIOLATIONS FROM GLUTATHIONE SYSTEM AT THE PATIENTS WITH
NONALCOHOLIC STEATOHEPATITIS ON A BACKGROUND OF DIABETES MELLITUS TYPE II].
AB - At the patients with nonalcoholic steatohepatitis on a background of diabetes
mellitus type II, after completion of the generally accepted medical treatment
there was no normalization of indexes of the glutation system (the level of
recovered glutation and activity of enzymes the glutation redox-system was saved
decreased), that in a clinical plan was represented in.a presence unstable
clinical and biochemical remission of disease.
PMID- 27491149
TI - [EXPRESSION OF PFKFB, HK2, NAMPT, TSPAN13 AND HSPB8 GENES IN PEDIATRIC GLIOMA].
AB - We studied the peculiarity of the expression of several key genes related to
dysregulation of cell proliferation and surviving processes in pediatric glioma
(glioblastoma multiforme) tissue from five children with age from 5 to 8 years as
well a sin corresponding nonmalignant tissue counterparts as control from the
same patients. RNA was isolated from glioma tissue and corresponding non
malignant tissue counterparts and PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT,
TSPAN13, and HSPB8 gene expressions were studied by quantitative polymerase chain
reaction. It was shown that the expression level of genes PFKFB1, PFKFB2, PFKFB3,
PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8 is increased in pediatric gliomas as
compared to corresponding non-malignant tissue counterparts, but in different
grade. More significant changes were demonstrated for PFKFB3, PFKFB4 HK2, NAMPT,
TSPAN13, and HSPB8 genes. Thus, the changes in pediatric glioma tissues of the
expression of PFKFB1, PFKFB2, PFKFB3, PFKFB4, HK2, NAMPT, TSPAN13, and HSPB8
genes, which control cell proliferation and apoptosis, possibly contribute to
enhance the tumor growth, because these genes control cell proliferation and
surviving.
PMID- 27491152
TI - [THE LEVELS OF OSTEOCALCIN AND PYRIDINOLINE IN PATIENTS WITH SYSTEMIC LUPUS
ERYTHEMATOSUS: THE RELATIONSHIP WITH STRUCTURAL AND FUNCTIONAL STATE OF BONE
TISSUE AND COURSE OF THE DESEASE].
AB - The article presents data on levels of osteocalcin and pyridinoline in patients
with systemic lupus erythematosus (SLE), their comparison with structural and
functional state of bone tissue and course of the disease. Bone metabolism
derangements were found in 65.8% of women with SLE. Herewith, the increase of
pyridinoline content was observed in 43.9% of patients, the reduction of
osteocalcinin 39% of individuals. The deterioration of bone metabolism was
associated with the severity of the disease, especially high levels of C-reactive
protein (CRP) and interleukin-6 (IL-6) (r = 0.3-0.32), cumulative dose of
glucocorticoids (GC) and low body mass index (BMI). Among patients with signs of
biosynthetic inhibition and increasing of destructive processes in bone tissue
were more often met people with osteopenia and osteoporosis. osteoporosis.
PMID- 27491151
TI - [THE APPLICATION OF ANTIHOMOTOXIC DRUG PREPARATIONS IN THE COMPLEX TREATMENT IN
PATIENTS WITH NEUROLOGICAL MANIFESTATIONS OF LUMBAR OSTEOCHONDROSIS].
AB - The expediency of application homeosyniatry by preparations of Traumel S and
Placenta Compositum after the offered chart in relation to a complex with classic
acupuncture and in relation to the group of the generally accepted treatment has
been proved in complex treatment patients with reflex syndromes of lumbar
osteochondrosis. A similar conclusion was done after the statistically reliable
(P < 0.05) dynamics of parameters of endogenous intoxication, liperoxydation and
antioxydant systems of the protection (by the level of katalase,
superoxyddismutase, SH-groups, ceruloplasmine).
PMID- 27491153
TI - [THE ROLE OF OSTEOCALCIN IN COURSE OF OSTEOARTHRITIS AND TYPE 2 DIABETES
MELLITUS].
AB - We studied the level of osteocalcin and its relationships with carbohydrate
metabolism and clinical and radiographic changes in patients with osteoarthritis
(OA) and type 2 diabetes mellitus (DM 2) and their combination. Significant
negative correlation between the level of osteocalcin and carbohydrate
metabolism, and clinical and radiographic changes in patients with OA and DM 2
was found. We determined, that negative correlation of osteocalcin with
carbohydrate metabolism and radiographic changes, and more pronounced pain in OA
maybe an indication that the lack of production of osteocalcin leads to more
severe changes during the OA on the background of DM 2 diabetes mellitus.
PMID- 27491154
TI - [METHODS IN ABDOMINAL OBESITY].
AB - This article describes the anatomical and physiological, histological and
topographic features of adipose tissue on the relationship of metabolic syndrome,
insulin resistance and cardiovascular disease. An advanced diagnostic techniques
of total body fat and visceral fat content quantification as the most
metabolically active are described.
PMID- 27491155
TI - [THE INFLUENCE OF A COMBINATION OF MODERN DRUGS NUCLEINAT AND ALFAGIN ON THE
CONCENTRATION OF CIRCULATING IMMUNE COMPLEXES AND THEIR MOLECULAR COMPOSITION IN
THE SERUM OF PATIENTS WITH IRRITABLE BOWEL SYNDROME ON THE BACKGROUND OF
NEUROCIRCULATORY DYSTONIA IN COMPLEX MEDICAL REHABILITATION].
AB - The effect of the combination nucleinat and alfagin in a complex of medical
rehabilitation at the level of circulating immune complexes (CIC) in serum of
patients and their molecular composition with irritable bowel syndrome (IBS),
against neurocirculatory dystonia (NeD). It is established that the combination
of nucleinat and alfagin in medical rehabilitation of patients with this comorbid
disorders contributes to the normalization of the total concentration of the CEC
and their molecular composition, which indicates the validity of the application
of the pathogenesis combinations of drugs in complex medical rehabilitation of
patients with lBS against NCD.
PMID- 27491156
TI - [COMPARATIVE EVALUATION OF THE EFFECTIVENESS OF THE USE OF 13C-LABELED MIXED
TRIGLYCERIDE AND 13C-STARCH BREATH TESTS IN PATIENTS WITH CHRONIC PANCREATITIS
AFTER CHOLECYSTECTOMY].
AB - The results of a comprehensive study of 96 patients after cholecystectomy are
provided. The higher sensitivity and informativeness of the 13C-labeled mixed
triglyceride breath .test compared with 13C-starch breath test for determining
functional pancreatic insufficiency in patients after cholecystectomy in early
stages of its formation was set.
PMID- 27491157
TI - [THE LEVEL OF LACTATE DEHYDROGENASE AS A MARKER OF RENAL DYSFUNCTION IN NEONATES
WITH ASPHYXIA].
AB - The article examines the possibility of determining the level of lactate
dehydrogenase (LD) in biological fluids as a marker of renal dysfunction and
energy supply in neonates with asphyxia. Investigation included 200 full-term
newborns with disturbance kidney function: 100 infants who had severe asphyxia,
and 100--with moderate asphyxia. LD activity was determined by kinetic
spectrophotometric method. Determination of the activity of LD in the urine in
the early neonatal period it is advisable to use as a non-invasive marker for the
diagnosis of renal dysfunction in neonates with asphyxia. The content of LD in
the blood serum can be used as one of the early markers of kidney damage in
newborns with asphyxia.
PMID- 27491158
TI - [A MODERN APPROACH TO THE TREATMENT OF DIABETIC POLYNEUROPATHY].
AB - In this paper, the authors conducted research on the application of a new drug
for the treatment of diabetic polyneuropathy in patients with diabetes mellitus
type 1 and 2. Established an effective influence on the hemodynamic, metabolic,
biochemical parameters, improved sensory-motor conduction in nerve fibers.
Recommended for widespread use in patients with diabetes mellitus.
PMID- 27491159
TI - [FEATURES MICROECOLOGY GENITAL TRACT IN WOMEN OF REPRODUCTIVE AGE WITH BENIGN
CERVICAL PATHOLOGY].
AB - In the article we may see the results of microbiological investigation of
secretion from genital tracts in women with the benign pathology of uterus
cervix. The outcomes specify the disorders of microecology of genital tracts in
these women following the proliferation of conditionally pathogenic flora, the
increase of viral infection and the increase in the frequency of diagnostic of
sexually transmitted infections.
PMID- 27491160
TI - [ULTRASOUND CRITERIA OR THE OPERABILITY AND EFFICACY OF THE TREATMENT OF THE
MALIGNANT EPITHELIAL OVARIAN TUMOURS].
AB - In order to isolate the main sonographic criteria of ovarian cancer operability
the dynamical U.S. examination was performed on 65 women with epithelial tumors
of II-III stages before and during 5 years after treatment beginning, which
included (in different combinations) cytoreductive surgery and neoadjuvant
chemotherapy. Only total 14 (21.5%) relapses were revealed. The U.S. prognostic
criteria of the ovarian cancer treatment efficacy with and without neoadjuvant
chemotherapy were defined.
PMID- 27491161
TI - [STUDY EFFECT OF ASSOSIATED PATHOLOGY ON THE DEVELOPMENT OF OPTIC NERVE ATROPHY].
AB - Studied effect of assosiated pathology on the development of optic nerve atrophy
(ONA). The basis of population study was comparison some factors in the groups
with ONA and without ONA (analysis case-control) and evaluation of relative risk.
Analysis showed that the risk of development of ONA increased in coronary heart
disease, hypertension, diabetes, atherosclerosis. A functional-organizational
model of care for patients with ONA was proposed.
PMID- 27491162
TI - [THE MANIFESTATIONS OF THE PATHOLOGICAL CHANGES OF THE INTERNAL ORGANS IN
PATIENTS WITH DISEASES OF TEMPOROMANDIBULAR JOINT].
AB - The results of a survey of 248 patients (mean age--26.0 years +/- 7.4 years),
from which 222 patients (mean age--26.3 years +/- 8.0 years) with diseases of
temporomandibular joint. Identified and visceral connection between the local
changes in the iris, the state of the body's connective tissue, the presence of
visceral disease (cardiovascular, respiratory, digestive, urinary system),
diseases of the temporomandibular joints. Key words: temporomandibular joint,
connective tissue, iris, iridodiagnostic, internal organs, concomitant diseases,
topical. diagnostics.
PMID- 27491163
TI - [EVALUATION OF CHANGES OF GEOMETRICAL PARAMETERS OF ALGINATE DENTAL IMPRESSIONS
DUE TO THE INFLUENCE OF CHEMICAL AND MICROWAVE DISINFECTION METHOD USING 3D
TECHNOLOGIES].
AB - This clinical and laboratory study evaluated the effect of two methods of
disinfection in different modes at the volume changes of alginate dental
impressions and plaster models poured from them, as compared to the same
parameters of plastic master models (PMM), using three-dimensional non-contact
laser scanner and software. Immersion chemical disinfection for 15 min, microwave
disinfection at 354 W for 10 minutes and combined disinfection with the power of
319 W for 4 minutes did not significantly affect the volumetric dimensional
accuracy of the alginate impressions (P > 0.05).
PMID- 27491164
TI - [INVESTIGATION OF THE LEVEL OF MINERAL DENSITY OF SKELETAL OSSEOUS TISSUE IN
PATIENTS WITH PERIODONTAL TISSUE DISEASES].
AB - Results of investigation of mineral density condition of skeletal osseous tissue
in patients with inflammatory and dystrophic-inflammatory diseases of periodontal
tissues with ultrasound densitometry method have been presented. Various changes
of osseous tissue of skeletal bones have been detected: osteopenia, osteoporosis
and osteosclerosis, which correlated with the severity of pathological process in
periodontium. Analysis of the obtained results has been carried out depending on
patients' sex as well as form and severity degree of the course of periodontal
diseases. It has been established that the peak of detected impairments of
mineral density in the skeleton is due to osteopenia, the degree of severity of
which deteriorates with the severity of pathological process in periodontal
tissues, especially in women.
PMID- 27491165
TI - [CHANGING THE PHYSIOLOGICAL PROPERTIES OF ORAL LIQUID FOR OBESITY].
AB - The study of oral fluid homeostasis is a valuable noninvasive technique for
diagnosing the general state of the organism, as well as the initial stages of
the pathological processes in the tissues oral cavity. The results of studies of
changes in the physiological properties of the oral fluid (pH, salivary flow
rate, viscosity) in obesity.
PMID- 27491166
TI - [THE CORRECTION WITH NOOPHEN OF AUTONOMIC DYSFUNCTION IN YOUNG MEN WITH
HYPERTENSION].
AB - The aim of this study was to investigate the influence of antihypertensive
therapy with adding of gamma-amino-beta-phenylbutyric acid hydrochloride on the
autonornic regulation of tcardiovascular system and the psychoemotional status in
young men with hypertension. The study included 58 male with hypertension, aged
18-39 years (mean age 31.7 yearst 2.3 years), of them 28 patients (group I)
administered beta-blocker and the other received a complex therapy which included
beta-blocker and gamma-amino-beta-phenylbutyric acid hydrochiotide--Noofen
("OlainFarm", Latvia) 250 mg 3 times a day for 4 weeks. The control group
consisted of 20 healthy indi&iduals aged 18-39 years (mean age 31.5 years +/- 2.5
years). The examination included of standard clinical; biochemical and
instrumental investigatIons. We conducted a clinical measurement of blorid
pressure, ambulatory blood pressure monitoring (ABPM), Doppler echocardiography,
heart rate variability, autononlic symptoms questionnaire and Spielberger--Hanina
Anxiety Scale. Analysis of circadian blbod pressure profile arid autonomic
nervous system state in young men with hypertension, in spite of the short
disenle history demonstratnl violations of the blood pressure circadian rhythm
associated with the violation of the autonomic regulation of cardiovascular
system as indreased sympathetic activity and decreased parasympathetic activity
heart tate. In hypertensive patients with autonomic dysfunction we noted a
reduction of level of mental health, which was reflected in an increase in'the
number of people with high and moderate levels of reactive and personal anxiety
It has been demonstratedthat the use of combination therapy with adding Noofen in
young hypertensive men and autonomic dysfunction helped significantly improve the
HRV parameters and restore autonomic balance on time parameters of heart rate
variability reduced the level of reactive anxiety and imprdved the
psychoemotional state.
PMID- 27491169
TI - [EXPERIMENTAL GROUNDS ON POSSIBILITY TO MAKE AND TO USE PREDICTION MODELS OF
PESTICIDES DESIGN STANDARD IN THE WATER OF PONDS USED FOR HOUSEHOLD AND DRINKING
WATER SUPPLY].
AB - Taking into account the fact that current calculation methods for substantiation
of standards in the water of water reservoirs valid in Ukraine are outdated the
aim of our research was to scientifically substantiate the possibility to make
and to use prediction models of pesticides design standard in the water of ponds
used for household and drinking water supply. Array of experimentally
substantiated and approved to use in Ukraine maximum allowable concentrations
(MAC) of organic pesticides active ingredients in the water was analyzed (n =
201). Analysis of dependence between MAC value of pesticides in the water and its
physical and chemical properties, indices of ecotoxicological hazard and
persistency in the water was carried out using correlation and regression
analysis methods. Twelve regression equations to establish design value of
pesticides MAC in the water were proposed on the grounds of performed analysis.
The results of reliability testing of proposed procedure on pesticides design
tentatively allowable levels (TAL) in the water indicate on needs to apply the
least value of TAL obtained in the process of calculations using proposed
equations. It was proved that mathematical models proposed for prediction of
pesticide design standard in the water are adequate and significant by Fisher's
test (P < 0.05). Proposed algorithm allows considerably simplify procedure of
obtaining temporary hygienic standard in the water for new pesticides.
PMID- 27491167
TI - [EFFICIENCY OF COCARNIT IN COMPLEX THERAPY OF PATIENTS WITH SYSTEM DISEASES OF
CONNECTING FABRIC WITH DEFEAT OF MYOCARDIUM AND DISPLAYS OF CARDIAC
INSUFFICIENCY].
AB - In clinical trial included 41 patient with clinic-instrumental dates, which said
about myocardium dysfunction and system diseases of connecting fabric and
displays of CCI I-III of functional class (FC). Including of complex metabolic
drug Cocarnit in standard therapy of systemdiseases of connecting fabric was
instrumental in more expressed clinical improvement of patientsclinical dates in
15 days of supervision: a weakness diminished on 66.67%, shortbreathing at the
insignificant physical loading--on 23.81%, at the ordinary physical loading--on
47.62%, at the megascopic physical loading--on 19.05%, pain in area of heart--on
42.85%, there are interruptions in-process heart--on 28.57%, oedematousness of
shins--on 57.14%, sense of numbness, burning, sensitiveness to cold of
extremities--on 57.14%. Quantity of patients with III FC diminished on 5
(23.81%), in a control group--on 2 (10%). It implementation of test with the 6
minute walking more expressed increase of the overcame distance is set for the
patients of basicgroup--on 15.46% as compared to a control group--on 7.01%.
Cocarnit patients estimatedpositively; side effects with subsequent abolition of
drug, were not. Laboratory indexes (AlAT, AsAT, bilirubin, kreatinine,
haemoglobin) at the end of trial did not change considerably, that confirmed good
bearableness of drug.
PMID- 27491168
TI - [CHANGES IN THE METABOLISM IN THE MYOCARDIUM OF RATS WITH ARTERIAL HYPERTENSION].
AB - In the myocardium of the rats with arterial hypertension marked increase in the
amount of unsaturated fatty acids and polyunsaturated fatty acids. Reducing the
concentration of palmitic acid and increased levels of arachidonic acid is
considered as one of the factors that lead to the development of energy deficit
and oxidative stress. In rats, with hypertension myocardial lactate concentration
increases in the cytoplasmic fraction and reducing the amount of ATP. The level
in the cytoplasmic and mitochondrial fractions above benchmarks, indicating about
the change of antioxidant systems of the body In the cytoplasm and mitochondria
of cardiomyocytes of the rats with arterial hypertension marked decrease in the
activity of antioxidant enzymes: NO-synthase, catalase, glutathione reductase,
which causes metabolic changes of the myocardium.
PMID- 27491170
TI - [DEVELOPMENT OF THE LOCAL CLINICAL PATHWAY "PREVENTION OF CARDIOVASCULAR DISEASE"
(SCIENTIFIC STATEMENT AND PRACTICAL APPROACH)].
AB - An overview of scientific data on current approaches to the prevention of
cardiovascular diseases has been exposed. The results of proceedings on
development of the local clinical pathway "Prevention of cardiovascular disease"
in the State Institution of Science "Research and Practical Center of Preventive
and Clinical Medicine" State Administrative Department has been generalized.
PMID- 27491171
TI - [EPIDEMIOLOGIC ASPECTS OF HUMAN GRANULOCYTIC ANAPLASMOSIS IN THE WESTERN REGION
OF UKRAINE].
AB - This article presents data of complex study of human granulocytic anaplasmosis
the human granulocytic anaplasmosis (HGA) in the western region of Ukraine.
Natural HGA foci were identified, where the prevalence of A. phagocytophilum in
the main vector (I. ricinus) amount to (12.0 +/- 0.7) %, and seroprevalence of
HGA among the healthy population--(28.6 +/- 1.6) %. It's shown that A.
phagocytophilum is the etiologic agent of (33.7 +/- 4.9) % of undiagnosed cases
of seasonal febrile diseases. Principal characteristics of HGA epidemiology:
spring-summer scasonality, the prevalence of disease in the age structure of
people of active age (45.30 +/- 1.95 years), a significant level combination with
(60.4 +/- 2.2) % Lyme-horreliosis and other tick-borne infections (mixed
infections), the different level of activity of HGA epidemic process in forest
and steppe geographical landscape zones--were revealed.
PMID- 27491172
TI - [Early achievements of the Danish pharmaceutical industry--8. Lundbeck].
AB - The article series provides a written and pictorial account of the Danish
pharmaceutical industry's products from their introduction until about 1950. Part
8 deals with products from Lundbeck. Lundbeck which today is known as a
considerable international pharmaceutical company could in 2015 celebrate its 100
years' jubilee. Among the early Danish medicinal companies H. Lundbeck & Co. is
in many ways an exception as the company was not originally established as a
pharmaceutical company. Not until several years after the foundation the company
began to import foreign ready-made medicinal products and later-on to manufacture
these medicinal products in own factory and even later to do research and
development of own innovative products. When Lundbeck was established in 1915
several Danish medicinal companies, not only the well-known such as Alfred Benzon
and Lovens kemiske Fabrik (LEO Pharma), but also Skelskor Frugtplantage, Ferrin
and Ferraton, had emerged due to the respective enterprising pharmacy owners who
had expanded their traditional pharmacy business and even with commercial
success. Other medicinal companies, such as C.R. Evers & Co., Leerbeck & Holms
kemiske Fabriker, Chr. F. Petri, Erslevs kemiske Laboratorium, Edward Jacobsen,
Th. Fallesen-Schmidt, and yet other companies which were named after the founder
had all been established by pharmacists with the primary intention to manufacture
and sell medicinal products. Also for the limited companies Medicinalco,
Ferrosan, Pharmacia, and GEA the primary task was to manufacture and sell
medicinal products, and also in these companies pharmacists were involved in the
foundation. Not until 1924, fully 9 years after the foundation, Lundbeck started
to be interested in medicinal products and initiated import and sale of foreign
medicinal products manufactured by a.o. German and French companies which had not
established their own sales companies in Denmark. Almost all contemporary Danish
manufacturers of medicinal products could exclusively determine own proprietary
names of the articles and could themselves make their own homogeneous and easily
recognisable design, a.o. by frequent use of prefixes as Afa, Asa, Gea, Ido, Leo,
and Meco which associated to for instance the company name. However, it goes
without saying that Lundbeck had to market the articles in commission according
to the different contracts with their partners. Consequently their range of
products appeared heterogeneously. The international financial crisis and the
consequent unemployment in the 1920s and 1930s had in Denmark a.o. resulted in
national regulation in order to complicate import of ready-made goods and thus
support the domestic manufacture of such articles. This was one of the reasons
why Lundbeck decided to initiate its own manufacture of medicinal products in
Denmark instead of continuing only with the import business which had been
obstructed by the authorities. This article does not mention all Lundbeck's
medicinal products which were marketed in Denmark until 1955 where a new Pharmacy
Act came into force though undoubtedly a lot of interest can be written about all
of them. The products mentioned in this article have been carefully selected, not
only because they are representative for Lundbeck's development during the first
decades, but also because the Danish Collection of the History of Pharmacy has
acquired consumer packages of many of the articles. Several of these packages
include patient information leaflets with an instruction for use and/or other
information, and especially these leaflets represent a source material which has
not previously been given much attention. It does not appear from the available
source material whether these earliest medicinal products from Lundbeck were
assembled in Danish packages on the production sites, or whether they were
repacked in Copenhagen. It is not unlikely that the assembling originally was
finalized abroad, and that instructions for the production of packaging material
with Danish text were supplied by Lundbeck to the respective manufacturers.
However, it is not unlikely either that the currency restrictions which were made
after 1932 encouraged Lundbeck, where possible, first of all to import raw
materials and bulk products and then manufacture the finished products in Valby.
This was the case with Anusol, which Lundbeck certainly emphazised in the
advertisement. It has to be pointed out that at that time there were no legal
requirements regarding dating, neither of the user instructions nor of
advertisements. Thus it is not due to mistakes or omissions made by Lundbeck that
these materials are undated. The user instructions which Lundbeck had inserted in
the packages were made and distributed at a time where no legal restrictions were
in force neither regarding form nor content of such. The user instructions for
products marketed after 1932 had probably been presented to the Pharmacopoeia
Commission as this was statutory. It is, however, uncertain whether the
Commission has dealt with the contents and the look of the user instructions. The
most important task of the Commission was besides of the work with maintaining
the Pharmacopoeia to look after the economic interests of the pharmacies so that
only new drug substances could be marketed by the pharmaceutical industry, cf.
below. In order to find out whether, and if so to which extent, the Pharmacopoeia
Commission has been occupied in evaluating the informative and promoting printed
matters of the industry, would require studies of the unprinted files of the
Commission, and that is outside the scope of this article. At that time it was
not against the law to inform in a user instruction that in case of a longer
period of treatment, it would be more economical for the patient to buy a larger
package. If you look at these patient information leaflets with today's eyes in
the light of the present detailed, comprehensive and rigid regulations which the
EU Commission has stated regarding patient information leaflets, you will find
that Lundbeck's patient information leaflets were both simple and easy to read.
On a free sample of Gelonida meant for the prescribing physician Lundbeck stated,
besides of indication, dosage and warnings, also that the article was
"Manufactured in Denmark". At that time it was not required to print information
of production sites on packaging materials, however, it was not unusual to use
this sales promoting claim in times of unemployment. In 1949 the original
packaging material for Beatin was modified because certain text elements, the
therapeutic indications were removed as it appeared that they since 1933 had
violated the Pharmacy Act against advertisements for medicinal products aimed at
the public. The packaging material for Beatin is a model example of the
possibilities to combine practical information about the use of a medicinal
product with sales claims in a reliable way. The above text modification and thus
the legalisation of the packaging material took place upon request from the
company as the violation of the advertising rules of the Pharmacy Act apparently
had not resulted in any legal problems. Studies of unpublished files from the
National Board of Health may possibly explain the background of this sequence of
events, however, that is outside the scope of this article. The paragraph of the
Pharmacy Act of 1932, stating that a medicinal product containing a common
commodity as the active ingredient could not be marketed as a proprietary
medicinal product, was meant to protect the pharmacies against the increasing
competition from the industry. At first the paragraph did put a strain on the
industry which from then on either had to manufacture own originator products or
to copy other originator products without breaking patents. In the long run it
has probably caused that not only Lundbeck, but also other Danish pharmaceutical
companies became research-oriented and thus have been able to develop a
relatively large number of originator products. In this context a product like
Lucamid can hardly be regarded as an example of such a compulsory development of
an originator product, an acetylsalicylic acid analogue. There were already such
products on the market, but the wish to develop a better active ingredient has
probably been bigger. From the three first editions of The Tariff of Medicines
from 1935, 1937 and 1939 respectively it appears how Lundbeck's business within
the area of medicines developed during the last half of the 1930s. In 1935
Lundbeck had placed 36 different medicinal products on the market, and all of
them were in-licensing products. 4 years later, in 1939 Lundbeck had placed 40
different medicinal products on the market, and the number of in-licensing
products had been reduced to 18 and 22 products were Lundbeck products. However,
the increased focus on the development of own new medicinal products as Epicutan
and Klianyl did not stop the in-licensing activities. Varex which Lundbeck
brought on the market in 1942 came from a German pharmaceutical company with
which Lundbeck had not previously collaborated. In Denmark Lundbeck had the
intention to market 4 of Goedecke's 6 different medicinal products which all had
Gelonida as part of the proprietary name. However, only one of these products got
a longer life and with a simplified name, namely Gelonida. The fixed combination
with three compounds of acetylsalicylic acid, phenacetin and codeine was without
doubt effective, however, already at the end of the 1950s concern was raised
about the safety of phenacetin. The Card Index of Medicines is a primary source
of knowledge of how Lundbeck marketed the earliest medicinal products to the
prescribing physicians. (ABSTRACT TRUNCATED)
PMID- 27491173
TI - "We're Not Done".
PMID- 27491174
TI - Working Feverishly to FEND OFF DENGUE.
PMID- 27491175
TI - THE CONFIDENCE BOOSTER.
PMID- 27491176
TI - "Brexit is no quick fix for the NHS's problems".
PMID- 27491177
TI - Nurses' views on impact of referendum revealed.
PMID- 27491179
TI - Study looks at health visiting key attributes.
PMID- 27491178
TI - What would voting to leave or stay in the EU mean for nursing?
PMID- 27491180
TI - Most student nurses drop out at end of course or before it starts.
PMID- 27491181
TI - DH announces plans to dissolve nursing policy unit to cut costs.
PMID- 27491182
TI - London Assembly votes to fight against plans to scrap bursary.
PMID- 27491184
TI - Are black and minority ethnic nurses discriminated against?
PMID- 27491183
TI - Nursing staff removed from duty by trust.
PMID- 27491185
TI - "Wise use of our resources will improve hospital dementia care".
PMID- 27491186
TI - How dementia differs from normal ageing.
AB - Dementia is a collective name for a set of symptoms that include memory loss,
mood changes, confusion and increasing difficulty with everyday tasks. This four
part series provides an overview of dementia and its treatment, from its causes
and pathophysiology to diagnosis and the nurse's role in its management. This
first article reviews the main forms of dementia and how research is shedding new
light on the differences between dementia and normal ageing.
PMID- 27491187
TI - Developing a clinical research career.
AB - The National Institute for Health Research helps to promote clinical research
careers for health professionals working in clinical practice, and has developed
a structure to support new researchers. This article explains how nurses can get
involved in clinical research and the support available to them.
PMID- 27491188
TI - Evidence base for managing neurogenic bowel dysfunction.
PMID- 27491189
TI - Management of pruritus in palliative care.
AB - Pruritis (severe itching of the skin) is a relatively rare symptom in palliative
care, but it can have a negative impact on patients' physical, psychological and
social wellbeing. It can also be distressing for family members. Holistic
assessment is needed to inform an individual plan of care to alleviate the
itching, which will involve general skin-care measures and a combination of
topical and systemic treatments.
PMID- 27491190
TI - 60 seconds with Paula Crick.
PMID- 27491191
TI - Leading future leaders.
PMID- 27491192
TI - The fall of Theranos and the future of science in Silicon Valley.
PMID- 27491193
TI - HOW TO BEAT THE VIRUS--AND THE MOSQUITOES THAT CARRY IT.
PMID- 27491194
TI - So should we just kill them all?.
PMID- 27491195
TI - Wicked Problem Solvers.
AB - Companies today increasingly rely on teams that span many industries for radical
innovation, especially to solve "wicked problems." So leaders have to understand
how to promote collaboration when roles are uncertain, goals are shifting,
expertise and organizational cultures are varied, and participants have clashing
or even antagonistic perspectives. HBS professor Amy Edmondson has studied more
than a dozen cross-industry innovation projects, among them the creation of a new
city, a mango supply-chain transformation, and the design and construction of
leading-edge buildings. She has identified the leadership practices that make
successful cross-industry teams work: fostering an adaptable vision, promoting
psychological safety, enabling knowledge sharing, and encouraging collaborative
innovation. Though these practices are broadly familiar, their application within
cross-industry teams calls for unique leadership approaches that combine
flexibility, open-mindedness, humility, and fierce resolve.
PMID- 27491196
TI - Leading the Team You Inherit.
AB - Most leaders don't have the luxury of building their teams from scratch. Instead
they're put in charge of an existing group, and they need guidance on the best
way to take over and improve performance. Watkins, an expert on transitions,
suggests a three-step approach: Assess. Act quickly to size up the personnel
you've inherited, systematically gathering data from one-on-one chats, team
meetings, and other sources. Reflect, too, on the business challenges you face,
the kinds of people you want in various roles, and the degree to which they need
to collaborate. Reshape. Adjust the makeup of the team by moving people to new
positions, shifting their responsibilities, or replacing them. Make sure that
everyone is aligned on goals and how to achieve them--you may need to change the
team's stated direction. Consider also making changes in the way the team
operates (reducing the frequency of meetings, for example, or creating new
subteams). Then establish ground rules and processes to sustain desired
behaviors, and revisit those periodically. Accelerate team development. Set your
people up for some early wins. Initial successes will boost everyone's confidence
and reinforce the value of your new operating model, thus paving the way for
ongoing growth.
PMID- 27491197
TI - The Secrets of Great Teamwork.
AB - Over the years, as teams have grown more diverse, dispersed, digital, and
dynamic, collaboration has become more complex. But though teams face new
challenges, their success still depends on a core set of fundamentals. As J.
Richard Hackman, who began researching teams in the 1970s, discovered, what
matters most isn't the personalities or behavior of the team members; it's
whether a team has a compelling direction, a strong structure, and a supportive
context. In their own research, Haas and Mortensen have found that teams need
those three "enabling conditions" now more than ever. But their work also
revealed that today's teams are especially prone to two corrosive problems: "us
versus them" thinking and incomplete information. Overcoming those pitfalls
requires a new enabling condition: a shared mindset. This article details what
team leaders should do to establish the four foundations for success. For
instance, to promote a shared mindset, leaders should foster a common identity
and common understanding among team members, with techniques such as "structured
unstructured time." The authors also describe how to evaluate a team's
effectiveness, providing an assessment leaders can take to see what's working and
where there's room for improvement.
PMID- 27491199
TI - House Republicans' win on ACA lawsuit doesn't change much--yet.
PMID- 27491198
TI - How to Preempt Team Conflict.
AB - Team conflict can add value or destroy it. Good conflict fosters respectful
debate and yields mutually agreed-upon solutions that are often far superior to
those first offered. Bad conflict occurs when team members simply can't get past
their differences, killing productivity and stifling innovation. Destructive
conflict typically stems not from differences of opinion but from a perceived
incompatibility between the way certain team members think and act. The
conventional approach to working through such conflict is to respond to clashes
as they arise. But this approach routinely fails because it allows frustrations
to build for too long, making it difficult to reset negative impressions and
restore trust. In their research on team dynamics and experience working with
executive teams, Toegel and Barsoux have found a proactive approach to be much
more effective. In this article, they introduce a methodology that focuses on how
people look, act, speak, think, and feel. Team leaders facilitate five
conversations--one focused on each category--before the team gets under way, to
build a shared understanding of the process, rather than the content, of work and
lay the foundation for effective collaboration.
PMID- 27491200
TI - Clinton's Medicare buy-in concept revives debate on public option.
PMID- 27491201
TI - Aetna, Anthem face shareholder rebuke over political spending.
PMID- 27491202
TI - When the addict is a doctor.
PMID- 27491203
TI - Institutional investors fight for more sway at healthcare companies.
PMID- 27491204
TI - What, me buy insurance?.
PMID- 27491205
TI - Medical science's debt to the hibakusha.
PMID- 27491206
TI - Effective population health strategies require leadership diversity.
PMID- 27491207
TI - Making 3-D medical imaging a reality.
PMID- 27491208
TI - 'I certainly don't think Obamacare is going away, nor would I want it to'.
PMID- 27491209
TI - Overcoming the Next Barriers to Successful Therapy.
PMID- 27491210
TI - Brain Targeting in MPS-IIIA.
AB - Mucopolysaccharidosis type IIIA (MPS-IIIA) is a childhood metabolic
neuropathology caused by the inherited deficiency of the lysosomal enzyme
sulfamidase and is characterized by the accumulation of undegraded
glycosaminoglycans in the lysosomes of cells and tissues of affected patients.
MPS-IIIA represents one of the most common forms of lysosomal storage disorders
(LSDs) and to date there is no cure. Since neurodegeneration is the most relevant
pathological feature in MPS-IIIA patients, the treatment of the central nervous
system (CNS) lesions represents the goal of any effective therapy for this
devastating disorder. During the last years many advances have been made in
developing and testing new therapies for brain involvement in MPS-IIIA. These
studies have been possible because of the availability of mouse and dog models
that recapitulate the MPS-IIIA neuropathological features. Some of these
approaches are based on direct CNS administration routes through which the
therapeutic molecules access the CNS via the parenchyma (intracerebral
injections) or via the cerebrospinal fluid (intraventricular/intrathecal
injections). These approaches are highly invasive and poorly suited for clinical
use. Minimally invasive approaches are based on systemic injections into the
blood stream of therapeutics capable of crossing the blood-brain barrier (BBB).
This review will present the background of the clinic and pathology aspects of
MPS-IIIA and will describe the current MPS-IIIA preclinical and clinical studies
focusing on how a systemic therapeutic strategy based on crossing the BBB has
been successfully used to treat CNS pathology and behavioral abnormalities in a
mouse model of MPS-IIIA. Future clinical applications of this approach to MPS
IIIA patients will be also discussed together with the possibility of using
similar strategies in other LSDs with neurological involvement.
PMID- 27491212
TI - Prevention is the Best Therapy: The Geneticist's Approach.
AB - Abstract During the last two decades prenatal genetic screening and diagnosis has
become the cornerstone of medical care for family planning to prevent genetic
disease. Carrier screening programs for genetic disorders that are prevalent in
various populations identify couples and pregnancies at risk of having an
affected child. These couples can proceed with a choice of invasive prenatal
diagnosis tests of the fetus (chorionic villous sampling and amniocentesis), or
non-invasive prenatal testing of free fetal DNA circulation in the maternal blood
which has emerged within the last few years and is currently available for fetal
sexing for X Linked disorders. Despite the advances in prenatal diagnosis,
couples found to have a fetus affected with a genetic disorder may need to face
the dilemma of pregnancy termination. Preimplantation genetic diagnosis (PGD) is
an alternative to preempt risk of having a child affected with a life-altering
genetic disorder. This technique allows biopsy and genetic diagnosis of embryos
obtained from in vitro fertilization by analysis of the genetic material from one
or a few embryonic cells. Only unaffected embryos are returned to the mother to
establish the pregnancy. We present our experience using PGD for four Lysosomal
storage disorders: Tay Sachs, Gaucher type 1, Hunter and Fabry disease with some
of the couples being carriers of more than one genetic disorder. PGD is
applicable to most disorders for which the gene and the familial mutation are
known and should be presented to couples as an alternative to invasive prenatal
testing.
PMID- 27491211
TI - Combination Therapies for Lysosomal Storage Diseases: A Complex Answer to a
Simple Problem.
AB - Abstract Lysosomal storage diseases (LSDs) are a group of 40-50 rare monogenic
disorders that result in disrupted lysosomal function and subsequent lysosomal
pathology. Depending on the protein or enzyme deficiency associated with each
disease, LSDs affect an array of organ systems and elicit a complex set of
secondary disease mechanisms that make many of these disorders difficult to fully
treat. The etiology of most LSDs is known and the innate biology of lysosomal
enzymes favors therapeutic intervention, yet most attempts at treating LSDs with
enzyme replacement strategies fall short of being curative. Even with the advent
of more sophisticated approaches, like substrate reduction therapy, pharmacologic
chaperones, gene therapy or stem cell therapy, comprehensive treatments for LSDs
have yet to be achieved. Given the limitations with individual therapies, recent
research has focused on using a combination approach to treat LSDs. By coupling
protein-, cell-, and gene- based therapies with small molecule drugs, researchers
have found greater success in eradicating the clinical features of disease. This
review seeks to discuss the positive and negatives of singular therapies used to
treat LSDs, and discuss how, in combination, studies have demonstrated a more
holistic benefit on pathological and functional parameters. By optimizing routes
of delivery, therapeutic timing, and targeting secondary disease mechanisms,
combination therapy represents the future for LSD treatment.
PMID- 27491213
TI - Juvenile NCL (CLN3 Disease): Emerging Disease-Modifying Therapeutic Strategies.
AB - Abstract Juvenile Neuronal Ceroid Lipofuscinosis is a lysosomal storage disease
characterized pathologically by intracellular accumulation of autofluorescent
storage material and neurodegeneration. Caused by mutations in the CLN3 gene on
chromosome 16p12, the precise functions of the encoded protein remain unclear.
Yet, recent preclinical discovery has established new therapeutic targets in
development, including immunosuppressants, anti-inflammatories, and gene
replacement therapies. Development of robust clinical trial endpoints appropriate
for this poly-symptomatic disease, clinical trial design optimized for small
samples, and adequate and efficient participant recruitment are challenges that
lay ahead.
PMID- 27491215
TI - Types A and B Niemann-Pick Disease.
AB - Two distinct metabolic abnormalities are included under the eponym Niemann-Pick
disease (NPD). The first is due to the deficient activity of the enzyme acid
sphingomyelinase (ASM). Patients with ASM deficiency are classified as having
types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit
hepatosplenomegaly, frequent pulmonary infections, and profound central nervous
system involvement in infancy. They rarely survive beyond two years of age. Type
B patients also have hepatosplenomegaly and progressive alterations of their
lungs, but there are usually no central nervous system signs. The age of onset
and rate of disease progression varies greatly among type B patients, and they
frequently live into adulthood. Recently, patients with phenotypes intermediate
between types A and B NPD also have been identified. These individuals represent
the expected continuum caused by inheriting different mutations in the ASM gene
(SMPD1). Patients in the second category are designated as having type C NPD.
Impaired intracellular trafficking of cholesterol causes type C NPD, and two
distinct gene defects have been found. In this chapter only types A and B NPD
will be discussed.
PMID- 27491216
TI - CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis).
AB - CLN2 disease is an inherited metabolic storage disorder caused by the deficiency
of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The disease affects
mainly the brain and the retina and is characterized by progressive dysfunction
of the central nervous system, leading to dementia, epilepsy, loss of motor
function and blindness. The classical late infantile type begins at around three
years of age with epilepsy and/or a standstill of psychomotor development,
followed by a rapid loss of all abilities and death in childhood. A late onset
form in a small proportion of patients starts at the age of 4 to 10 years, but
also leads to severe neurological deterioration. The deficiency of TPP1 causes
the lysosomal accumulation of a material called ceroid lipofuscin. The natural
substrate of TPP1 is not known, nor is the connection between storage process and
neurodegeneration, which is characterized by loss of neurons. Among various
experimental approaches to treatment, enzyme replacement therapy (ERT) and gene
therapy have developed remarkably. Enzyme delivery through the cerebrospinal
fluid led to wide distribution of enzyme activity in the brain and to attenuated
neuropathology and disease progression in a TPP1-deficient mouse model as well as
in a natural TPP1-deficient dog model. Safety of the intrathecal delivery,
pharmacokinetics, and tissue distribution of the administered enzyme studied in
non-human primates were encouraging, and a phase I/II clinical trial for
intraventricular ERT in CLN2 patients is ongoing. A second approach uses
intracerebral injection of viral vectors containing normal coding segments of the
CLN2 gene. In a CLN2 mouse model, this procedure resulted in cerebral enzyme
expression, reduced brain pathology and increased survival. A small number of
patients have been treated the same way using an AAV2-vector for gene transfer to
the brain. Although there were no serious adverse events unequivocally
attributable to the vector used, there were some serious adverse effects, and a
clinical benefit was not clearly evident under the conditions of the experiment.
A phase I/phase II study using a AAVrh10 vector is presently recruiting patients.
PMID- 27491214
TI - The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy.
AB - The gangliosidoses are lysosomal storage disorders caused by accumulation of GM1
or GM2 gangliosides. GM1 gangliosidosis has both central nervous system and
systemic findings; while, GM2 gangliosidosis is restricted primarily to the
central nervous system. Both disorders have autosomal recessive modes of
inheritance and a continuum of clinical presentations from a severe infantile
form to a milder, chronic adult form. Both are devastating diseases without cure
or specific treatment however, with the use of supportive aggressive medical
management, the lifespan and quality of life has been extended for both diseases.
Naturally occurring and engineered animal models that mimic the human diseases
have enhanced our understanding of the pathogenesis of disease progression. Some
models have shown significant improvement in symptoms and lifespan with enzyme
replacement, substrate reduction, and anti-inflammatory treatments alone or in
combination. More recently gene therapy has shown impressive results in large and
small animal models. Treatment with FDA-approved glucose analogs to reduce the
amount of ganglioside substrate is used as off-label treatments for some
patients. Therapies also under clinical development include small molecule
chaperones and gene therapy.
PMID- 27491217
TI - Insights into the Pathogenesis and Treatment of Krabbe Disease.
AB - Krabbe disease (globoid cell leukodystrophy, GLD) is an inherited disease caused
by a deficiency in the lysosomal enzyme galactocerebrosidase (GALC). The major
galactosylated lipid degraded by GALC is galactosylceramide. However, GALC is
also responsible for the degradation of galactosylsphingosine (psychosine), a
highly cytotoxic glycolipid. It has been hypothesized that GALC-deficiency leads
to psychosine accumulation that preferentially kills oligodendrocytes in the
central nervous system and Schwann cells in the peripheral nervous system. Krabbe
disease has traditionally been considered a white matter disease characterized by
the loss and disorganization of myelin, infiltration of multinucleated
monocytes/macrophages (globoid cells) and lymphocytes, and dysregulation of pro
inflammatory cytokines and chemokines. However, new studies have revealed
unexpected neuronal deficiencies. Infantile Krabbe disease is believed to be the
most common and aggressive form. However, juvenile and adult onset forms have
been described. Children affected with infantile Krabbe disease present with
motor dysfunction, cognitive decline, intractable seizures, and premature death
between two to five years of age. Murine, canine, and primate models of GALC
deficiency have been described and have played an important role in our
understanding of this invariably fatal disease. Although there is no cure for
Krabbe disease, hematopoietic stem cell transplantation can slow the progression
of disease. Recent pre-clinical data indicate that simulataneously targeting
multiple pathogenic mechanisms greatly increases efficacy in the murine model of
Krabbe disease. A better understanding of the underlying pathogenesis will
identify new therapeutic targets that may further increase efficacy.
PMID- 27491218
TI - Therapy Development for the Lysosomal Storage Disease Fucosidosis using the
Canine Animal Model.
AB - Abstract Fucosidosis (OMIM 23000) is an inherited neurodegenerative lysosomal
storage disease caused by a deficiency of the lysosomal hydrolase a-L-fucosidase
due to mutations in the FUCA1 gene. Without enzyme-targeted therapy patients
rarely survive beyond the first decade of life, and therapy options other than
supportive care are limited. Hematopoietic transplants, first developed in the
fucosidosis dog model, are the only treatment option available capable of
delaying the disease course. However, due to the risks and exclusion criteria of
this treatment additional therapies are required. The development of additional
therapies including intravenous and intra-cerebrospinal fluid enzyme replacement
therapy and gene therapy, which have been trialed in the canine model, will be
discussed.
PMID- 27491219
TI - [Clinical Guidelines for Diagnosis and Treatment of Liver Injury Related to
Chinese Herbal Medicine].
PMID- 27491221
TI - [Study on the Distribution of Constitutions of Chinese Medicine in Patients with
Osteonecrosis of Femoral Head].
AB - OBJECTIVE: To observe the distribution of constitution types of Chinese medicine
(CM) in patients with osteonecrosis of femoral head (ONFH). METHODS: Totally 130
ONFH patients were recruited. Constitution types of CM were identified in all
patients. Distribution features of constitution types of CM in ONFH patients were
observed. The differences of distribution in gender, age, single or bilateral
hips, course of disease, staging, cause, and region were also analyzed. RESULTS:
Seventy patients were of complicated constitutions, while 60 patients were of
single constitution. Among the 60 single constitution cases, yang-deficiency
constitution [18 (13.9%)], damp-heat constitution [10 (7.7%)], blood-stasis
constitution [7 (5.4%)], and qi-deficiency constitution [7 (5.4%)] were mainly
distributed. Of the complicated constitutions, yang-deficiency dominated
constitution occupied the top ratio [30 (23.1%)], followed by blood-stasis
dominated constitution [15 (11.5%)], damp-heat dominated constitution [9 (6.9%)].
By putting them together, yang-deficiency constitution occupied the top
constitution of CM [48 (36.9%)], followed by blood-stasis constitution [ 22
(16.9%)] and damp-heat constitution [19 (14.6%)]. The aforesaid three
constitutions accounted for 68.5% of the total. There were no statistical
distribution differences in gender, age, single or bilateral hips, course of
disease, staging, or cause. CONCLUSION: Yang-deficiency constitution, damp-heat
constitution, and blood-stasis constitution were liable constitutions of CM in
ONFH patients.
PMID- 27491220
TI - [Effects of Scalp Acupuncture on Serum NSE and S-100beta Concentrations and
Postoperative Cogni- tive Function of Elderly Patients Undergoing Hip
Replacement].
AB - OBJECTIVE: To explore the effect of Scalp acupuncture on serum neuron specific
enolase (NSE) and S-100beta concentrations, and incidence rates of postoperative
delirium (POD) and postoperative cognitive function (POCD) of elderly patients
undergoing hip replacement. METHODS: Eighty-four patients undergoing scheduled
hip replacement under combined spinal-epidural anesthesia (CSEA) were assigned to
the control group (group C) and the scalp acupuncture group (group S) according
to random digit table, 42 cases in each group. In group S, scalp acupuncture was
additionally performed according to International Standardized Scheme for Scalp
Acupuncture. Scalp acupuncture was performed during the operation from the MS1
middle line of forehead [1 cun before Shenting (GV24), including Shenting (GV24)]
and MS5 middle line of vertex [from Baihui (DU20) to Qianding (DU21), including
Baihui (DU20) and Qianding (DU21)]. The operation time and post-operative length
of stay were observed. The midazolam dosage, hemorrhage amount, fluid transfusion
amount, urine amount, use rates of ephedrine and atropine during the operation
were also observed and compared between the two groups. The occurrence rate of
POD and POCD at post-operative day 3 (T1), week 1 (T2), month 3 (T3), and month 6
(T4) were measured. Eighteen patients were randomly selected to collect blood
from internal jugular vein before anesthesia t0), immediately after ending the
surgery (t1), 6 h after operation (t2), 24 h after operation (t3), and 48 h after
operation (t4), respectively. Serum levels of NSE and S-100beta were
correspondingly measured. RESULTS: There was no statistical difference in the
operation time, midazolam dosage used during the operation, hemorrhage amount,
fluid transfusion amount, urine amount, use rates of ephedrine and atropine (P >
0.05). Compared with group C, the post-operative length of stay was shortened in
group S (P < 0.05). The incidence rate of POD and that of POCD at each time point
were lower in group S (P < 0.05). The expression level of NSE decreased at t2,
t3, and t4, and the expression level of S100beta also decreased at t1, t2, t3,
and t4(P < 0.05). There was no statistical difference in expression levels of NSE
or S100beta between the two groups at other time points (P > 0.05). CONCLUSION:
Scalp acupuncture could attenuate central nervous system lesion and improve POCD
of elderly patients undergoing hip replacement.
PMID- 27491222
TI - [Efficacy Observation for Treating Ankylosing Spondylitis by Chinese Herbs and
Recombinant Hu- man Tumor Necrosis Factor Receptor II-Antibody Fusion Protein].
AB - OBJECTIVE: To observe the clinical effect of Chinese medical (CM) syndrome
differentiation based Chinese herbs and recombinant human tumor necrosis factor
receptor II-antibody fusion protein (etanercept) for treating ankylosing
spondylitis (AS) patients. METHODS: Totally 35 AS patients were treated with
syndrome differentiation based Chinese herbs and etanercept. Reinforcing Shen and
strengthening Du channel, activating meridians to stop pain was principle used in
syndrome differentiation based treatment. Etanercept was subcutaneously injected,
25 mg each time; twice per week for the first three months and once a week for
the latter three months. The clinical efficacy was evaluated after 3 and 6 months
of treatment. Meanwhile, ASAS20 and ASAS50 standards arriving rates were also
observed. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath
Ankylosing Spondylitis Functional Index (BASFI), visual analog score (VAS) for
spine pain, VAS for night pain, patient global assessment (PGA), VAS for
physician global assessment, CM syndrome score, finger-ground distance, thoracic
activity, tragus-wall distance, lumbar scoliosis, cervical rotation, Schober
improved test, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)
were observed before treatment, 3 and 6 months after treatment. RESULTS: Compared
with before treatment, BASDAI, BASFI, VAS for spine pain, night pain, physician
global assessment, PGA, CM syndrome score, finger-ground distance, thoracic
activity, tragus-wall distance, lumbar scoliosis, Schober improved test, ESR, and
CRP all decreased after 3 and 6 months of treatment, with statistical difference
(P < 0.05). Cervical rotation also decreased after 6 months of treatment, with
statistical difference (P < 0.05). Compared with 3 months of treatment, total
effective rate of CM syndrome, ASAS20 and ASAS50 standards arriving rates
increased after 6 months of treatment, with statistical difference (P < 0.05).
There were statistical differences in all indices mentioned above between after 3
months of treatment and after 6 months of treatment (P < 0.05). CONCLUSION:
Syndrome differentiation based Chinese herbs combined etanercept could alleviate
inflammatory reaction favorably, control the progression of active AS, and
improve joint functions.
PMID- 27491223
TI - [Research on Life Quality Scale for Patients with Idiopathic Pulmonary Fibrosis].
AB - OBJECTIVE: To develop a life quality scale suitable for idiopathic pulmonary
fibrosis (IPF) patients, objectively reflecting its changes. METHODS: Authors
first put forward a theoretical structure model of a scale according to patient
reported outcome (PRO) scale formulation principle by combining basic theories of
Chinese medicine (CM). Then authors developed an initial scale on the basis of
various life quality scales for respiratory disease patients by using structural
decision making. Totally 34 patients with confirmed diagnosis of IPF were tested
by questionnaire. Items were screened using expert importance scoring method,
factor analysis, correlation coefficient method, Cronbach's alpha coefficient
method. IPF patient reported outcomes (IPF PRO, IP) were finally defined.
RESULTS: A new IP scale was developed covering three areas and 38 items. Pearson
correlation coefficient for correlation analysis of clinical symptom scores in ST
George Respiratory Questionnaire and IP scale was 0.828 (P < 0.01). Pearson
correlation coefficient for correlation analysis of activity ability scores was
0.929 (P < 0.01). Pearson correlation coefficient for correlation analysis of
total scores was 0.862 (P < 0.01). By reliability of IP scale itself
(reliability) analysis, Cronbach's alpha coefficient was 0.713. By using factor
analysis method for data analysis, KMO statistics was 0.902. CONCLUSION: IP scale
fully reflected the connotation of IPF patients' quality of life, so it could be
used as CM clinical therapeutic effect evaluation tool.
PMID- 27491224
TI - [Treatment of Early Diabetic Retinopathy by Liuwei Dihuang Pill Combined Ginkao
Leaf Tablet].
AB - OBJECTIVE: To observe the prevention and clinical efficacy of combination of
Liuwei Dihuang Pill (LDP) and Ginkgo Leaf Tablet (GLT) for early diabetic
retinopathy (DR). METHODS: Using randomized, double-blind, double simulation,
parallel controlled clinical trial, 140 type 2 diabetes mellitus (T2DM)
outpatients were recruited and assigned to the treatment group and the control
group, 70 in each group. All patients received basic Western medicine treatment
(such as blood glucose and pressure control). Patients in the treatment group
took LDP (8 pills each time, 3 times per day) and GLT (19.2 mg each time, 3 times
per day), while those in the control group took LDP placebos and GLT placebos.
All treatment lasted for 24 consecutive months. All subjects were followed-up
every month. The general clinical data as sex, age, and metabolic data such as
blood glucose, blood pressure, blood lipid, and DR prevalence rate were collected
and statistically analyzed. RESULTS: There was no significant difference in
levels of blood glucose, blood pressure, or blood lipid between the two groups (P
> 0.05). After treatment the DR incidence rate was significantly lower in the
treatment group than in the control group [3.1% (2/64) vs 18.6% (11/59), P <
0.05)]. Meanwhile, the DR prevalence rate of the treatment group was also
significantly lower than that of the control group [6.3% (4/64) vs 20.0% (13/59),
P < 0.05]. CONCLUSION: Combination of LDP and GLT could effectively prevent and
treat the development of DR in T2DM patients.
PMID- 27491225
TI - [Distribution of Syndrome Types of Chinese Medicine in Acute Infectious
Diarrhea].
AB - OBJECTIVE: To observe syndrome types of Chinese medicine (CM) and distribution
features of acute infectious diarrhea patients. METHODS: A retrospective study
was performed in 465 acute infectious diarrhea patients. The distribution of CM
syndrome and syndrome types in different seasons and genders were analyzed.
RESULTS: Lack of appetite [381 (81.94%)], fatigue [350 (75.27%)], abdominal pain
[338 (72.69%)], tenesmus [325 (69.89%)], anal scorching hot [276 (59.35%)],
nausea [25 (55.48%)], diarrhea [249 (53.55%)], short yellow-urine [240 (51.61%)],
thirsty [210 (45.16%)], and abdominal distention [206 (44.30%)] were most often
seen. The syndrome distribution were sequenced as intestinal damp heat syndrome
[268 (57.63%)], dyspeptic retention in intestine and stomach syndrome [106
(22.80%)], cold-damp invading exterior syndrome [47 (10.11%)], Pi-Wei qi
deficiency syndrome [23 (4.95%)], cold-damp disturbing Pi syndrome [21 (4.52%)].
The incidence ratio of intestinal damp heat syndrome was the highest in autumn (P
< 0.01), while that of cold-damp invading exterior syndrome was the highest in
winter (P < 0.01). Cold-damp disturbing Pi syndrome was more often seen in
females than in males (P < 0.01), and its incidence ratio was the highest in
autumn (P < 0.05). The incidence ratio of dyspeptic retention in intestine and
stomach syndrome was the highest in winter (P < 0.01). CONCLUSIONS: Intestinal
damp heat syndrome was the most often seen in acute infectious diarrhea.
Incidence ratios of in- testinal damp heat syndrome and cold-damp disturbing Pi
syndrome were higher in autumn, while those of cold-damp invading exterior
syndrome and dyspeptic retention in intestine and stomach syndrome were higher in
winter. Cold-damp disturbing Pi syndrome was more often seen in females.
PMID- 27491227
TI - [Effects of Cangfu Congxian Decoction on Oxidative Stress in Polycystic Ovary
Syndrome Patients].
AB - OBJECTIVE: To observe the effect of Cangfu Congxian Decoction (CCD) on oxidative
stress in granulosa cells of polycystic ovary syndrome (PCOS) patients. METHODS:
Forty PCOS patients underwent in vitro fertilization-embryo transfer (IVF-ET)
were assigned to the treatment group and the control group 1 according to random
digit table, 20 in each group. Patients in the treatment group took CCD (200 mL,
once in the morning and once in the afternoon) 2 months before IVF-ET, while
those in the control group 1 took no Chinese medical decoction. Recruited were
another 20 patients undergoing IVF-ET for tubal factors (as the control group 2).
The clinical effect of IVF-ET were observed, including oocyte retrieval number, 2
pronuclear (2PN) fertilization rate, good quality embryo rate, clinical pregnancy
rate, and ovarian hyperstimulation syndrome (OHSS) induced transplantation cancel
rate. The expression of relative oxygen species (ROS) in granulosa cells was
detected using cell immunofluorescence combined with confocal microscopy and FCM.
RESULTS: Compared with the control group 1, occyte retrieval number, 2PN
fertilization rate, and good quality embryo rate increased in the control group 2
and the treatment group (P <0. 05). OHSS induced transplantation cancel rate
decreased in the control group 2 (P < 0.05). Fluorescence intensity of ROS
decreased in the treatment group and the control group 2, as compared with the
control group 1 (P < 0.01). CONCLUSION: CCD increased good quality embryo rate by
down-regulating the expression of ROS protein in ovarian granulosa cells, and
correcting in vivo oxidative stress.
PMID- 27491226
TI - [Therapeutic Effects of Berberine Capsule on Patients with Mild Hyperlipidemia].
AB - OBJECTIVE: To observe the therapeutic effects of Berberine Capsule (BC) on
patients with mild hyperlipidemia. METHODS: Totally 102 mild hyperlipemia
patients were recruited. All patients were suggested to have proper diet and
physical activity as basic therapy for 1 month of run-in period. Totally 97
patients completed it. Then they were randomly assigned to the berberine group
(the treatment group, 49 cases) and the placebo group (the control group, 48
cases). Patients in the treatment group took BC 300 mg, while those in the
control group took placebo 300 mg, thrice per day for 3 successive months. Then
placebos and BC were interrupted for 2 months (as washout period). All subjects
received only diet control and physical activity during washout period. After
washout period, placebos and BC were re-administered to all patients in the same
way for 3 months. Body mass index (BMI), fasting plasma glucose (FPG), TG, TC,
LDL-C, and HDL-C were assessed after run-in period, washout period, at month 1,
2, 3 after the first therapy, at month 1, 2, 3 after second treatment,
respectively. RESULTS: Compared with the end of run-in period, TG, TC, and LDL-C
decreased, and HDL-C increased in the treatment group (P < 0.05) after first 3
months of treatment. Compared with 3 months after the first therapy, TG, TC, and
LDL-C increased and HDL-C decreased in the treatment group after washout period
(P < 0.05). Compared with the end of wash- out period, TC and LDL-C decreased in
the treatment group at month 2 after second treatment (P < 0.05); TG, TC, and LDL
C decreased (P < 0.01, P < 0.05), and HDL-C increased (P < 0.05) at month 3 after
second treatment. Compared with the control group at month 3 after second
treatment, TG, TC, and LDL-C all decreased, and HDL-C increased in the treatment
group (all P < 0.05). CONCLUSION: BC was effective in improving blood lipid level
in mild hyperlipidemia patients.
PMID- 27491228
TI - [Analgesic Effect and Mechanism of Electroacupuncture on Rats with Chronic
Inflammatory Pain].
AB - OBJECTIVE: To observe analgesic effect of electroacupuncture ( EA) on rats with
chronic inflammatory pain and its regulatory mechanism on ispilateral dorsal root
ganglion (DRG) and spinal dorsal horn (SDH) Mas-related G protein-coupled C
receptor (MrgprC). METHODS: Totally 40 healthy male SD rats were divided into 4
groups according to random number table, i.e., the normal (N) group, the model
(M) group, the acupuncture (Acu) group, the EA group, 10 rats in each group. The
model of chronic inflammatory pain was established by subcutaneous injecting 0. 1
mL complete Freund's adjuvant (CFA) into right hind paw. Paw withdrawal
thresholds (PWTs) were measured before modeling, at day 1, 3, 5, 7, and after CFA
injection, respectively. Expression levels of MrgprC in ispilateral DRG and SDH
were detected by Western blot. The content of bovine adrenal medulla 22 (BAM22)
in SDH was detected by immunohistochemical assay. RESULTS: Compared with N group
at each time point, PWTs significantly decreased in M group (P <0. 01). Compared
with M group, PWTs significantly increased at day 5 of EA and after EA in EA
group (P < 0.05, P < 0.01). Compared with Acu group at each time point, post-EA
PWTs significantly increased in the EA group (P < 0.05). Compared with N group,
expression of MrgprC in ispilateral DRG and ratio of BAM22 positive cells in
ispilateral SDH increased in M group (P < 0.01). Compared with M group,
expression of MrgprC in ispilateral DRG and ratio of BAM22 positive cells in
ispilateral SDH increased in the EA group (P < 0.05). CONCLUSION: EA had
favorable analgesic effect on chronic inflammatory pain induced by CFA, and its
mechanism might be possibly associated with up-regulating MrgprC expression in
ispilateral DRG and BAM22 content in ispilateral SDH.
PMID- 27491229
TI - [Effect of Borneol on the Permeability of Blood Tumor Barrier Model and its
Mechanism Study].
AB - OBJECTIVE: To observe the effect of natural borneol on the permeability of blood
tumor barrier (BTB) model and the expression and activation of mitogen-activated
protein kinase (MAPKs) signal transduction pathway related protein kinase in
vitro. METHODS: C6 rat glioma cells and human umbilical vein endothelial cells
(HUVECs) were co-cultured to establish BTB model. Then 4 groups were set up, the
blank control group, low, middle, and high dose borneol groups (25, 50, 100
ug/mL), 3 samples collected at 7 time points (0, 10, 30, 60, 120, 180, 240 min,
respectively). Blank culture medium was exchanged in the blank control group
while medication. Different doses of natural borneol were administered to the 3
borneol groups. Cells were collected at different time points. BTB permeability
was determined using horseradish peroxidase (HRP). Expression levels of
extracellular signal regulated protein kinase (ERK), phosphorylation
extracellular signal regulated protein kinase (P-ERK), P38MAPK, phosphor-P38MAPK,
c-Jun N-terminal kinase (JNK), and phosphorylation c-Jun N-terminal kinase (P
JNK) were detected using Western blot. RESULTS: Compared with the same group at
min 0, the permeation rate obviously increased (P < 0.01) in the 3 borneol groups
at the rest time points. P-ERK expression was elevated first, reached the peak at
30 min, and gradually recovered to the initial level (P > 0.05). Compared with
the blank control group, HRP permeation rate increased from 10 min to 240 min (P
< 0.01), and expression of P-ERK protein increased at 30 min and 60 min (P <
0.05) in the low dose borneol group; expression of P-JNK protein decreased in the
3 borneol groups at 180 min and 240 min (P < 0.05). Compared with the low dose
borneol group, expression of P-ERK protein increased from 10 min to 180 min (P <
0.05), HRP permeation rate increased from 30 min to 180 min (P < 0.05),
expression of P-JNK protein decreased at 180 and 240 min (P < 0.05) in the middle
dose borneol group. Compared with the middle dose borneol group, HRP permeation
rate increased from 10 min to 180 min (P < 0.05), expression of P-ERK protein
increased from 10 min to 180 min (P < 0.05), expression of P-JNK protein
increased at 180 min and decreased at 240 min (both P < 0.05) in the high dose
borneol group. CONCLUSION: Natural borneol arrived at the effect of regulating
reversible BTB patency possibly through activating phosphorylation of ERK in
MAPKs signal transduction pathway, and further reversibly down-regulating
expression of associated proteins.
PMID- 27491230
TI - [Danlou Tablet Fought against Inflammatory Reaction in Atherosclerosis Rats with
Intermingled Phlegm and Blood Stasis Syndrome and Its Mechanism Study].
AB - OBJECTIVE: To observe the effects of Danlou Tablet (DT) on inflammatory reaction,
and expressions of lipoprotein-associated phospholipase A2 (LP-PLA2), secretory
phospholipase A2 (sPLA2), and to analyze potential mechanisms. METHODS: Forty
male Wistar rats were randomly and equally divided into five groups, i.e., the
normal control group, the model group, the Western medicine (WM) group, the low
dose DT group, the high dose DT group, 8 in each group. Rats in the normal
control group were fed with basic forage for 12 successive weeks, while AS rat
model was established in rats of the other four groups by feeding high fat and
sugar forage plus intraperitoneal injection of vitamin D3. Normal saline,
atorvastatin calcium suspension (at the daily dose of 1.8 mg/kg), low dose DT
suspension (at the daily dose of 450 mg/kg), and high dose DT suspension (at the
daily dose of 900 mg/kg) were administered to rats in the model group, the WM
group, the low dose DT group, the high dose DT group respectively by gastragavage
for 8 successive weeks. The general condition of all rats was observed. Rats were
sacrificed after gastric administration and their serum collected. Serum levels
of lipids (TC, TG, HDL-C, LDL-C) and inflammatory factors [IL-6, TNF-alpha,
monocyte chemoattractant protein 1 (MCP-1), oxidized low-density lipoprotein (ox
LDL), lipoprotein-associated phospholipase A2 (LP-PLA2), secretory phospholipase
A2 (sPLA2)] were detected. Pathological changes of thoracic aorta were observed
by HE staining. Protein and gene expressions of LP-PLA2 and sPLA2 in thoracic
aorta were measured by Western blot and real-time fluorescent quantitative PCR
respectively. RESULTS: Compared with the normal control group, rats in the model
group were in low spirits and responded poorly. Typical atherosclerotic plaque
could be seen in thoracic aorta of rats in the model group. Serum levels of TC,
TG, LDL-C, IL-6, TNF-alpha, MCP-1, ox-LDL, LP-PLA2, and sPLA2 significantly
increased (P < 0.05); protein and gene expressions of LP-PLA2 and sPLA2 in rat
thoracic aorta increased (P < 0.05) in the model group. After 8 weeks of
intervention, rats in 3 medication groups appeared active, and HE staining showed
subsidence of plaque in rat thoracic aorta. Compared with the model group, serum
levels of TC, TG, LDL-C, IL-6, TNF-alpha, MCP-1, ox-LDL, and LP-PLA2 decreased in
3 medication groups (P < 0.01, P < 0.05); serum sPLA2 level decreased, protein
and mRNA expressions of LP-PLA2 and sPLA2 in rat thoracic aorta decreased in the
WM group (P < 0.01, P < 0.05); protein and mRNA expressions of LP-PLA2 in rat
thoracic aorta significantly decreased in the low dose DT group (P < 0.01, P <
0.05), and those of LP-PLA2 and sPLA2 decreased in the high dose DT group (P <
0.01, P < 0.05). CONCLUSION: DT could fight against inflammatory reaction and AS
possibly through inhibiting LP-PLA2 expression and reducing ox-LDL production.
PMID- 27491231
TI - [Effect of Tongxinluo on Apoptosis of Rat Cardiac Microvascular Endothelial
Cells].
AB - OBJECTIVE: To observe the protective effects of Tongxinluo (TXL) on apoptosis of
rat cardiac microvascular endothelial cells (RCMECs) resulting from homocysteine
(Hcy) induced endoplasmic reticulum stress (ERS), and to determine the signaling
pathway behind its protection. METHODS: Primary cultured RCMECs were isolated
from neonatal rats using tissue explant method. The morphology of RCMECs was
observed using inverted microscope, identified and differentiated by CD31
immunofluorescence method. Selected were well growing 2nd-4th generations of
RCMECs. The optimal action time was determined by detecting the expression of
glucose regulated protein 78 (GRP78) using immunofluorescence method. In the next
experiment RCMECs were divided into 5 groups, i.e., the blank control group, the
Hcy induced group (Hcy 10 mmol/L, 10 h), the Hcy + TXL group (Hcy 10 mmol/L + TXL
400 ug/mL), the Hcy +LY294002 group (Hcy 10 mmol/L + LY294002 5 umol/L, LY294002
as the inhibitor of PI3K), the Hcy + LY294002 + TXL group (Hcy 10 mmol/L +
LY294002 5 umol/L + TXL 400 ug/mL). The apoptosis rate of RCMECs was detected by
flow cytometry. mRNA and protein expressions of GRP78, C/ EBP homologous protein
(CHOP), and cysteinyl aspartate specific proteinase-12 (caspase12) were detected
by real-time reverse transcription PCR (RT-PCR) and Western blot respectively.
Expression levels of phosphorylation of phosphatidylinositol 3-kinase (P-PI3K),
total phosphatidylinositol 3-kinase (T- P13K) , phosphorylation of kinase B (P
Akt) , and total kinase B (T-Akt) were detected by Western blot. RESULTS: Ten
hours Hcy action time was determined. Compared with the blank control group, the
apoptosis rate was increased (22.77%), mRNA and protein expressions of GRP78,
CHOP, and Caspase-12 were increased, protein expressions of P-PI3K and P
Akt,ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were decreased in the Hcy induced
group (P < 0.05, P < 0.01). Compared with the Hcy induced group, the apoptosis
rate was decreased (10.17%), mRNA and protein expressions of GRP78, CHOP, and
Caspase-12 were decreased, and expression levels of P-PI3K, P-Akt, P-PI3K/T-PI3K,
and P-Akt/T-Akt were increased in the Hcy + TXL group (P < 0.05, P < 0.01).
Compared with the Hcy + TXL group, the apoptosis rate was increased (17.9%), mRNA
and protein expressions of GRP78, CHOP, and Caspase-12 were increased, expression
levels of P-PI3K and P-Akt, ratios of P-PI3K/T-PI3K and P-Akt/T-Akt were
decreased in the Hcy + TXL + LY294002 group (P < 0.05, P < 0.01). CONCLUSION: TXL
could inhibit the apoptosis of RCMECs resulting from Hcy-induced ERS and its
mechanism might be associated with activating PI3K/Akt signaling pathway.
PMID- 27491232
TI - [Ligustrazine Promoted the Migration of Bone Marrow Mesenchymal Stem Cells by Up
regulating MMP-2 and MMP-9 Expressions].
AB - OBJECTIVE: To explore the effect of ligustrazine on the migration of bone marrow
mesenchymal stem cells (BMSCs) and protein expressions of matrix
metalloproteinase-2 and-9 (MMP-2 and MMP-9) in vitro. METHODS: BMSCs were in
vitro isolated and cultured using whole bone marrow adherent method, and
phenotypes [surface positive antigens (CD29 and CD90) and negative antigens (CD34
and CD45)] identified using flow cytometry. BMSCs were divided into the blank
control group, 25, 50, 100 umol/L ligustrazine group, and the GM6001 group (100
umol/L ligustrazine +MMPs inhibitor GM6001 ). The migration of BMSCs was tested
by Transwell chamber test and wound healing assay after treated with ligustrazine
for 24 h. The protein expressions of MMP-2 and MMP-9 were detected by Western
blot. RESULTS: The third passage BMSCs grew well in uniform morphology. The
expression rate of CD29, CD90, CD34, and CD45 was 96.9%, 97.3%, 0.2%, and 3.0%,
respectively. Compared with the blank control group, the number of migrated cells
and relative distance of cell invasion increased, and the protein expressions of
MMP-2 and MMP-9 were elevated in each ligustrazine group (P < 0.05, P < 0.01).
Compared with 100 umol/L ligustrazine group, the number of migrated cells and
relative distance of cell invasion decreased in 25 and 50 umol/L ligustrazine
groups and the GM6001 group (P < 0.01). Protein expression of MMP-2 decreased in
25 and 50 umol/L ligustrazine groups (P < 0.01). CONCLUSION: Ligustrazine could
promote the migration of BMSCs in vitro, and its mechanism might be related to up
regulating expression levels of MMP-2 and MMP-9 protein.
PMID- 27491233
TI - [Brain Protection of Muscone in Rats with Brain Injury].
AB - OBJECTIVE: To observe cerebral protective effect of muscone (nasal
administration) on traumatic brain injury model rats. METHODS: SD rats were
divided into the sham-operation group, the model group, and the treatment groups
according to random digit table, 50 in each group. Traumatic brain injury model
was established by controlled cortical strike. Rats in the sham-operation group
received surgery and anesthesia procedures only, with no strike. Muscone (1.8
mg/kg) was delivered to rats in the treatment group using in situ nasal
perfusion, 30 min each time, twice daily for 7 successive days. Water content of
brain tissue was detected in each group before intervention (T1), at day 3 of
intervention (T2), day 5 of intervention (T3), and after intervention (T4),
respectively. Expression levels of brain derived neurotrophic factor (BDNF) and
nerve growth factor (NGF) were detected using immunohistochemical analysis.
RESULTS: Compared with the sham-operated group, water content of brain tissue
increased (P < 0.05), and expression levels of NGF and BDNF decreased in the
model group at T1, T2, T3, and T4 (P <0. 01). Compared with the model group,
water content of brain tissue decreased (P < 0.05), and expression levels of NGF
and BDNF increased (P < 0.01) in the treatment group at T1, T2, and T3.
CONCLUSION: Nasal administration of muscone could reduce water content of brain
tissue, alleviate cerebral edema, promote secretion of BDNF and NGF by olfactory
ensheathing cells in traumatic brain injury rats.
PMID- 27491235
TI - [Effects of Jianpi Jiedu Recipe on TCRVbetaCDR3 Spectratyping of Liver Cancer
Rats with Pi Deficiency Syndrome].
AB - OBJECTIVE: To observe anti-cancer effects of Jianpi Jiedu Recipe (JJR) on liver
cancer (LC) rats with Pi deficiency syndrome (PDS) and its relation with the
third complementary-determining region gene spectratyping of TCRVbeta-chain
(TCRVbetaCDR3). METHODS: Rats were divided into 8 groups according to random
digit table, i.e., the blank control group (normal), the PDS group, the LC model
group, the LC-PDS group, high, middle, and low dose JJR groups (75.00, 37.50,
18.75 g/kg, respectively by gastrogavage, once per day), the thymus pentapeptide
group (5 mg/kg, intramuscular injection, twice per week), 8 in each group. Rats
in the normal group were administered with physiological saline by gastrogavage
once per day. PDS rat model was prepared by bitter-cold purgation. LC model was
prepared by orthotopic transplantation method. Twenty gene subfamilies of
TCRbetaCDR3 in the thymus, liver, and LC tissues were detected by Gene Scan.
RESULTS: High and middle dose JJR could postpone the growth of LC volume (P <
0.05), with equivalent liver index and thymus index to those of the normal group
(P > 0.05). In thymus and liver tissue of the normal group, the number of clones
(20 and 19), gene fragment number (220 and 113), Quasi-Gaussian distribution
ratio of TCRVbetaCDR3 gene repertoire (100.0% and 42.1%), and fragment
fluorescence peak area (6,539 +/- 2,325 and 1,238 +/- 439) were at the highest
level among the 8 groups. TCRVbetaCDR3 expressions in thymus and liver tissue of
high and middle dose JJR groups were approximate to those of the normal group.
They were in the middle of the thymus pentapeptide group, the PDS group, the LC
model group, and poorest in the LC-PDS group. TCRVbetaCDR3 in liver tissue
expressed the best in the thymus pentapeptide group. CONCLUSION: JJR might
inhibit the growth of LC cells, and its mechanism might be related to enhancing
TCRVbetaCDR3 spectratype expression.
PMID- 27491234
TI - [Inhibition of Combination of Icaritin and Doxorubicin on Human Osteosarcoma MG
63 Cells in vitro].
AB - OBJECTIVE: To explore the inhibition and molecular mechanism of icaritin (ICT)
combined doxorubicin (DOX) on human osteosarcoma MG-63 cells in vitro. METHODS:
The control group, ICT groups (10, 20, 40, 80, and 160 umol/L), DOX groups (1, 2,
4, 8, and 16 ug/mL), and combination groups (20 umol/ L ICT +1 ug/mL DOX, 20
umol/L ICT +2 ug/mL DOX, 20 umol/L ICT +4 ug/mL DOX, 40 umol/L ICT +1 ug/mL DOX,
40 umol/L ICT +2 ug/mL DOX, 40 umol/L ICT +4 ug/mL DOX, 80 umol/L ICT +1 ug/mL
DOX, 80 umol/L ICT +2 ug/mL DOX, 80 umol/L ICT +4 ug/mL DOX) were set up. Human
osteosarcoma MG-63 cells were respectively cultured and their effects on
morphological changes were observed using inverted phase contrast microscope
after 24-and 48-h intervention. The cell proliferation inhibition rate of each
group was de- termined using CCK-8, and IC50 calculated. The MG-63 apoptosis rate
was detected using Annexin V-FITC/ PI double dye flow cytometry. Expression
levels of bcl-2, caspase-3, and p21 were detected using RT-PCR. RESULTS: ICT and
DOX could obviously inhibit the proliferation of MG-63 cell. Along with ICT
concentration increasing from 10 umol/L to 160 umol/L, the cell proliferation
inhibition rate also increased gradually from 9.67% +/- 3.62% to 89.18% +/-
9.66%. The IC50 was 46.93 umol/L and 3.87 ug/mL respectively. ICT and DOX could
cause either early or late stage apoptosis, down-regulate Bcl-2 gene expression,
and up-regulate gene expressions of Caspase-3 and p21 respectively (P < 0.05).
Aforesaid changes were more obviously seen in combination groups than in lCT
groups and DOX groups (P < 0.05). CONCLUSION: CT combined DOX had additive or
synergistic inhibition effect for the proliferation of osteosarcoma MG-63 cells,
which might be related with regulating gene expressions of bcl-2, caspase-3, and
p21.
PMID- 27491236
TI - [Study on the Fingerprint of Kingkong Zedoary Turmeric Oil].
AB - OBJECTIVE: To study the fingerprint of Zedoary Turmeric Oil (ZTO) as the bulk
drug of Kingkong Elemene for making it safe, effective, stable, and controllable.
METHODS: Fingerprints were detected by gas chromatography. beta-elemene peak was
regarded as reference peak (S). The relative peak area of each common peak and
the relative retention time were calculated. With a total of modes for reference,
the fingerprints of 10 batches of Kingkong ZTO were detected, and their
similarity was calculated by traditional Chinese medicine (TCM) fingerprint
similarity calculation software. RESULTS: The determination method was stable and
reliable. Totally 19 common characteristic peaks of Kingkong ZTO was found. The
fingerprint similarity of these batches of Kingkong ZTO were not lower than 0.96.
CONCLUSIONS: Gas chromatography for detecting the fingerprint of Kingkong ZTO was
reliable and repeatable. The established fingerprint of Kingkong ZTO could
guarantee the quality stability and safety of different product batches.
PMID- 27491237
TI - [Staging Based Strategies and Practice for Prostate Cancer].
AB - Authors raised that staging based strategies and practice of integrative medicine
(IM) by combining syndrome typing and disease identification, and choosing
suitable measures in accordance with different persons and seasonal conditions
after more than ten years' clinical practice and researches. Radical operation as
prior (as evil eliminating) and strengthening vital qi in perioerative period are
best strategy for promoting rapid rehabilitation of early stage prostate cancer
patients. Strengthening body resistance to eliminate evil was used in treating
advanced prostate cancer patients. For example, a comprehensive treatment program
for hormone-dependent patients was combined with endocrinotherapy and Chinese
herbs for synergisic efficacy-enhancing actions. In this way, these patients'
quality of life (QOL) were improved and time to castration resistant prostate
cancer (CRPC) was delayed, even some patients were clinically cured. There are
lack of effective medicines and methods for CRPC patients. Greatly tonifying
original qi is mainly used for improving their clinical symptoms and prolonging
survivals. Practice has proved staging based strategies and practice of IM has
favorable advantages in treating prostate cancer, especially showing prospect in
prolonging survival and postponing progression of advanced prostate cancer
patients. Besides, it also could provide beneficial considerations and
inspiration for combination of syndrome typing and disease identification.
PMID- 27491238
TI - [Acupoint Selection Laws for Massage Therapy of Infantile Anorexia: an Analysis
Based on Data Mining].
AB - Massage prescriptions for treating infantile anorexia in Chinese Academic Journal
Full-Text Database (CNKI, 1979-2012), Chinese Scientific and Technological
Journal Full-Text Database (VIP, 1989-2012) and Wanfang Database (1990-2012) were
collected. By using Chinese Medicine Inheritance Auxiliary Platform (Version 2.0)
Software, 286 massage prescriptions for treatment of infantile anorexia were
screened involved 76 acupoints, 20 commonly used acupoints, and 57 core acupoint
combinations. Infantile Tuina specific points were used as main acupoints in
massage therapy for infantile anorexia, and core acupoints covered Jizhu, Pi
meridian, abdomen, Nei-Bagua, Zusanli (ST36), and Ban-men.
PMID- 27491239
TI - [Communicative Translation of Chinese Patent Medical Instruction].
PMID- 27491240
TI - [Progress of Chinese Medicine and Western Medicine in Diagnosis and Treatment of
Poor Ovarian Response in IVF-ET Cycle].
PMID- 27491241
TI - TALES FROM THE INSIDE.
PMID- 27491242
TI - INFLAMED.
PMID- 27491244
TI - 24 HOURS IN THE LIVES OF PEOPLE AFFECTED BY HIV.
PMID- 27491243
TI - A CALL TO ACTION BY THE TRANSGENDER COMMUNITY.
PMID- 27491246
TI - Editorial: EHealth Law: The Final Frontier?
PMID- 27491245
TI - DEAR DOCTOR... WHAT ABOUT CANCER? AND OTHER QUESTIONS ANSWERED.
PMID- 27491247
TI - Legal Status of Telemedicine in the Internal Market.
AB - Health services enjoy freedom of movement within the European Union (EU). This
freedom also applies to information society services (ISS). This article presents
a legal framework within which it is possible to provide qualifying health
services with the help of information and telecommunications technology (ICT) as
iss. Due to the ambiguity of EU regulation, the problem regarding how to
determine whether a particular medical service corresponds to favourable
structural iss conditions is considered. Since telemedicine makes a wide
application of electronic devices possible, a new element appears in the
relationship between physicians and their patients. Therefore, using electronic
devices may cause numerous doubts regarding the normative status of these
devices, since they modify the physician's responsibility and affect the scope of
his duty with regard to information. At the same time, the complexity of
functional elements (actions) necessary to provide health services using ICT can,
in some cases, prevent them from being recognised as ISS.
PMID- 27491248
TI - Data Protection Compliance in the Age of Digital Health.
AB - Advances in technology are transforming the way that health data is collected and
used. This includes improvements in existing technology as well as innovations in
mobile technology such as smartphone apps and wearables. Health data is strictly
regulated under the EU Data Protection Directive 95/46/EC. Under current data
protection rules, health data is broadly interpreted and will, in most
circumstances not connected to the provision of healthcare, require organisations
to obtain explicit consent from individuals for its collection and use. Further
data protection compliance issues arise such as identifying who is a controller,
ensuring transparency, using health data for research purposes and keeping health
data secure. As the EU data protection landscape is due to change in the next few
years and will affect the collection and use of health data, the forthcoming Data
Protection Regulation also deserves attention.
PMID- 27491249
TI - Electronic Health Record in Italy and Personal Data Protection.
AB - The present article deals with the Italian Electronic Health Record (hereinafter
EHR), recently introduced by Act 221/2012, with a specific focus on personal data
protection. Privacy issues--e.g., informed consent, data processing, patients'
rights and minors' will--are discussed within the framework of recent e-Health
legislation, national Data Protection Code, the related Data Protection Authority
pronouncements and EU law. The paper is aimed at discussing the problems arising
from a complex, fragmentary and sometimes uncertain legal framework on e-Health.
PMID- 27491250
TI - Exceptions and Exclusions: The Right to Informed Consent for Medical Treatment of
People with Psychosocial Disabilities in Europe.
AB - This article examines the relevant international law relating to informed consent
to treatment for individuals with psychosocial disabilities and reflects on the
protection offered in this respect by the European Convention on Human Rights
(ECHR) and the Council of Europe Convention on Human Rights and Biomedicine. The
article argues that while the UN Convention on the Rights of Persons with
Disabilities is beginning to influence case law of the European Court of Human
Rights, only 'weak' protection has been afforded to people with psychosocial
disabilities by the ECHR and the Court in relation to informed consent for
medical treatment.
PMID- 27491251
TI - European Court of Human Rights. ECHR 2016/14 Case of Vasileva v. Bulgaria, 17
March 2016, no. 23796/10 (Fifth Section).
PMID- 27491252
TI - European Court of Human Rights. ECHR 2016/15 Case of Elena Cojocaru v. Romania,
22 March 2016, no. 7417412 (Fourth Section).
PMID- 27491253
TI - European Court of Human Right. ECHR 2016/16 Case of Kolesnikovich v. Russia, 22
March 2016, no. 4469413 (Third Section).
PMID- 27491254
TI - European Court of Human Rights. ECHR 2016/17 Case of Blokhin v. Russia, 23 March
2016, no. 47152/06 (Grand Chamber).
PMID- 27491255
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Editorial:
Endocrine and metabolic emergencies].
PMID- 27491256
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics: I.
Acute adrenal insufficiency (Adrenal crisis)].
PMID- 27491258
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics: III.
Thyroid storm].
PMID- 27491257
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics II.
Pheochromocytoma crisis].
PMID- 27491259
TI - [Endocrine and Metabolic Emergencies: Points of Initial Management. Topics: IV.
Emergency medical care for patients with hypercalcemia or hypocalcemia].
PMID- 27491260
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics: V.
Hyponatremic encephalopathy].
PMID- 27491261
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics: VI.
Emergency treatment for eating disorders and refeeding syndrome].
PMID- 27491262
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics: VII.
Hypoglycemic coma].
PMID- 27491263
TI - [Endocrine and Metabolic Emergencies; Points of Initial Management. Topics: VIII.
Hyperglycemic emergencies].
PMID- 27491264
TI - [Case Report; A case of type B insulin-resistance syndrome ameliorated with
immune-suppression therapies].
PMID- 27491265
TI - [Case Report; A case of disseminated Mycobacterium shigaense infection].
PMID- 27491266
TI - [Case Report; A case of platypnea orthodeoxia syndrome after transcatheter
Amplatzer device closure in a patient with persistent foramen ovale].
PMID- 27491267
TI - [Case Report; A case of Streptococcus suis meningitis which caused bilateral
sensorineural hearing loss was improved due to the cochlear implantation].
PMID- 27491268
TI - [The Cutting-edge of Medicine; Latest evolution of family doctors' roles outside
of Japan].
PMID- 27491269
TI - [The Cutting-edge of Medicine; Innate immunity and autoimmune disease].
PMID- 27491270
TI - Nanobubble Skin Supersolidity.
AB - Water nanobubbles manifest fascinatingly higher mechanical strength, higher
thermal stability, and longer lifetime than macroscopic bubbles; thus, they
provide an important impact in applications in the biomedical and chemical
industries. However, a detailed understanding of the mechanism behind these
mysteries of nanobubbles remains a challenge. Consistency between quantum
computations and Raman spectrometric measurements confirmed our predictions that
a nanobubble skin shares the same supersolidity with molecular clusters, skins of
bulk water, and water droplets because of molecular undercoordination (fewer than
four nearest molecular neighbors). Molecular undercoordination (coordination
number Zcluster < Zsurface < Zbubble < Zbulk = 4) shortens/extends the H-O/O:H
bond and stiffens/softens its corresponding stretching phonons, whose frequency
shift is proportional to the square root of the cohesive energy and inversely
proportional to the segmental length. The strongly polarized O:H-O bond slows the
molecular dynamics and increases the viscosity. The freezing temperature is
lowered by the softened O:H bond, and the melting temperature is enhanced by the
stiffened H-O bond. Therefore, the supersolid skin makes the nanobubbles
thermally more stable, less dense, and stiffer and slows the dynamics of their
molecular motion.
PMID- 27491271
TI - Effect of hospital caseload on long-term outcome after standardization of rectal
cancer surgery in the Spanish Rectal Cancer Project.
AB - INTRODUCCIoN: The purpose of this prospective multicentre multilevel study was to
investigate the influence of hospital caseload on long-term outcomes following
standardization of rectal cancer surgery in the Rectal Cancer Project of the
Spanish Society of Surgeons. METHODS: Data relating to 2910 consecutive patients
with rectal cancer treated for cure between March 2006 and March 2010 were
recorded in a prospective database. Hospitals were classified according to number
of patients treated per year as low-volume, intermediate-volume, or high volume
hospitals (12-23, 24-35, or >=36 procedures per year). RESULTS: After a median
follow-up of 5 years, cumulative rates of local recurrence, metastatic recurrence
and overall survival were 6.6 (CI95% 5.6-7.6), 20.3 (CI95% 18.8-21.9) and 73.0
(CI95% 74.7 - 71.3) respectively. In the multilevel regression analysis overall
survival was higher for patients treated at hospitals with an annual caseload of
36 or more patients (HR 0,727 [CI95% 0,556-0,951]; P=.02). The risk of local
recurrence and metastases were not related to the caseload. Moreover, there was a
statistically significant variation in overall survival (median hazard ratio
[MHR] 1.184 [CI95% 1.071-1,333]), local recurrence (MHR 1.308 [CI95% 1.010
1.668]) and metastases (MHR 1.300 [CI95% 1.181; 1.476]) between all hospitals.
CONCLUSIONS: Overall survival was higher for patients treated at hospitals with
an annual caseload of 36 or more patients. However, local recurrence was not
influenced by caseload.
PMID- 27491272
TI - Carbon nanotube membranes to predict skin permeability of compounds.
AB - In the present study, carbon nanotube (CNT) membranes were prepared to predict
skin penetration properties of compounds. A series of penetration experiments
using Franz diffusion cells were performed with 16 different membrane
compositions for model chemicals. Similar experiments were also carried out with
same model molecules using five different commercially available synthetic
membranes and human skins for the comparison. Model chemicals were selected as
diclofenac, dexketoprofen and salicylic acid. Their permeability coefficients and
flux values were calculated. Correlations between permeability values of model
compounds for human skins and developed model membranes were investigated. Good
correlations were obtained for CNT membrane, isopropyl myristate-treated CNT
membrane (IM-CNT membrane) and bovine serum albumin-cholesterol, dipalmitoyl
phosphatidyl choline-treated membrane (BSA-Cholesterol-DPPC-IM-CNT membrane). An
artificial neural network (ANN) model was developed using some molecular
properties and penetration coefficients from pristine CNT membranes to predict
skin permeability values and quite good predictions were made.
PMID- 27491273
TI - Quirks of dye nomenclature. 6. Malachite green.
AB - Malachite green was discovered independently by two researchers in Germany in the
19(th) century and found immediate employment as a dye and a pigment.
Subsequently, other uses, such as staining biological specimens, emerged. A much
later application was the control of fungal and protozoan infections in fish, for
which the dye remains popular, although illegal in many countries owing to a
variety of toxicity problems. In solution, malachite green can exist as five
different species depending on the pH. The location of the positive charge of the
colored cation on a carbon atom or a nitrogen atom is still debated. The original
names of this dye, and their origins, are briefly surveyed.
PMID- 27491274
TI - The OH-Initiated Oxidation of CS2 in the Presence of NO: FTIR Matrix-Isolation
and Theoretical Studies.
AB - We studied the photochemistry of the carbon disulfide-nitrous acid system with
the help of Fourier transform infrared (FTIR) matrix isolation spectroscopy and
theoretical methods. The irradiation of the CS2...HONO complexes, isolated in
solid argon, with the filtered output of the mercury lamp (lambda > 345 nm) was
found to produce OCS, SO2, and HNCS; HSCN was also tentatively identified. The
(13)C, (15)N, and (2)H isotopic shifts as well as literature data were used for
product identifications. The evolution of the measured FTIR spectra with
irradiation time and the changes in the spectra after matrix annealing indicated
that the identified molecules are the products of different reaction channels:
OCS being a product of another reaction path than SO2 and HNCS or HSCN. The
possible reaction channels between SC(OH)S/SCS(OH) radicals and NO were studied
using DFT/B3LYP/aug-cc-pVTZ method. The SC(OH)S and/or SCS(OH) intermediates are
formed when HONO attached to CS2 photodissociates into OH and NO. The
calculations indicated that SC(OH)S radical can form with NO two stable adducts.
The more stable SC(OH)S...NO structure is a reactant for a simple one-step
process leading to OCS and HONS molecules. An alternative, less-stable complex
formed between SC(OH)S and NO leads to formation of OCS and HSNO. The
calculations predict only one stable complex between SCS(OH) radical and NO,
which can dissociate along two channels leading to HNCS and SO2 or HSCN and SO2
as the end products. The identified photoproducts indicate that both SC(OH)S and
SCS(OH) adducts are intermediates in the CS2 + OH + NO reaction leading to
different reaction products.
PMID- 27491275
TI - Type XIX collagen: A new partner in the interactions between tumor cells and
their microenvironment.
AB - Type XIX collagen is a minor collagen that is associated with the basement
membrane zone that belongs to the FACIT family (Fibril-Associated Collagens with
Interrupted Triple helices). The FACIT family is composed of type IX, XII, XIV,
XVI, XX, XXI, XXII and XIX collagens, which share many highly conserved
structural motifs: a short NC1 domain, a thrombospondin-like N-terminal domain
(TSPN), and numerous cysteine residues. The main role of FACITs is to ensure the
integrity and stability of the extracellular matrix and its fibrillar collagen
network by regulating the formation and size of the collagen fibrils. Type XIX
collagen was discovered in a human rhabdomyosarcoma cell line. The collagen
alpha1(XIX) chain is composed of 5 triple-helical domains (COL) interrupted by 6
non-triple-helical (NC) domains with a short, C-terminal, 19 amino acid non
collagenous domain (NC1). This collagen is involved in the differentiation of
muscle cells, central nervous system development, and formation of the esophagus.
Type XIX collagen is associated with the basement membrane zone, like type XVIII
and XV collagens. Its short NC1(XIX) C-terminal domain inhibits the migration and
invasion of melanoma cells. It also exerts a strong anti-angiogenic effect by
inhibiting MMP-14 and VEGF expression. NC1(XIX) binding to alphavbeta3 integrin
decreases the phosphorylation of proteins involved in the FAK (Focal Adhesion
Kinase)/PI3K (PhosphoInositide 3-Kinase)/Akt (protein kinase B)/mTOR (Mammalian
Target Of Rapamycin) pathway. On the other hand, NC1(XIX) induces an increase in
GSK3beta activity by decreasing its level of phosphorylation. The inhibition of
this pathway could explain the anti-tumor properties of the NC1(XIX) domain.
PMID- 27491276
TI - Simplified and standardized intrapartum management can yield high rates of
successful VBAC in spontaneous labor.
AB - OBJECTIVE: To examine the outcomes of vaginal birth after cesarean (VBAC) in
women, in spontaneous labor, delivering after 37 weeks' gestation at an
institution where trial of labor after a previous cesarean delivery (TOLAC) is
encouraged and management of labor is standardized. METHODS: This retrospective
cohort study included 3071 women with one previous cesarean only and no vaginal
delivery who underwent a trial of labor from 2001 to 2011. Women were managed
using the standardized "active management of labor" intrapartum protocol.
Outcomes and characteristics of women who delivered vaginally were compared with
those who required cesarean delivery. RESULTS: In spontaneous labor in their
second pregnancy, those who attempted TOLAC had a 72.5% (1611/2222) rate of
successful VBAC. Women who had a successful VBAC had smaller babies (3584 +/- 452
g versus 3799 +/- 489 g; p < 0.0001) at earlier gestations than those who had a
repeat intrapartum cesarean delivery. They also required less intrapartum
intervention, such as oxytocin augmentation (14.5% [234/1611] versus 41%
[251/611]; p < 0.0001) and epidural anesthesia (64.8% [1044/1611] versus 82.8%
[506/611]; p < 0.0001). The rate of uterine rupture was 0.54% (12/2222), while
the rate of peri-partum hysterectomy was 0.18% (4/2222). CONCLUSION: This study
shows that serious complications associated with TOLAC are rare providing
intrapartum care and decision-making is made simple for the benefit of staff and
patients alike. This is achieved through a standardized labor management
protocol.
PMID- 27491277
TI - Neuropsychological functioning in heart transplant candidates.
AB - OBJECTIVE: This study provides age stratified neuropsychological test data for a
large sample of heart transplant candidates. Patients with and without
neurological co-morbidities were compared to better isolate the effects of
congestive heart failure (CHF) on brain functioning. METHOD: Between 1988 and
2011, 956 patients (717 males, 239 females) with end-stage CHF and other life
threatening cardiac diseases underwent neuropsychological assessment as a
requirement of the heart transplant workup. Intellectual, memory, executive,
language, attentional and psychomotor abilities were assessed, and standard
cardiac measures were concurrently collected. Independent t-tests were used to
compare subgroups with and without neurological co-morbidities on cardiac,
neuropsychological and MMPI-2 measures. Chi-square tests were used for
categorical items to compare demographic data between the two groups. RESULTS:
Significant cognitive impairments across all domains assessed were typical in all
age groups. Neurological co-morbidities, such as CVA and cardiac arrest were
common, with 28% of the sample having one or more condition. That subgroup scored
lower on measures of processing speed, memory, and executive measures, but the
pattern of deficits was similar for both groups and not explainable by
depression. Depression prevalence per MMPI-2 findings was comparable to that of
the general population. CONCLUSIONS: End stage heart disease/heart failure is
associated with global, mild to moderate cognitive impairment, regardless of age
or neurological co-morbidities. Contributing factors likely include
cerebrovascular hypoperfusion, multiorgan failure, systemic co-morbidities, and
lifestyle issues.
PMID- 27491278
TI - Hospitalizations and Other Health Care Resource Utilization Among Patients with
Deep Vein Thrombosis Treated with Rivaroxaban Versus Low-molecular-weight Heparin
and Warfarin in the Outpatient Setting.
AB - PURPOSE: Compared with low-molecular-weight heparin (LMWH) and warfarin, the oral
anticoagulant rivaroxaban has advantages, such as simplified care, that may lead
to less health care resource utilization. METHODS: A retrospective, matched
cohort analysis was conducted using claims dated between January 2011 and
December 2013 from the Truven Health Analytics MarketScan databases. Adult
patients who had a primary diagnosis of deep vein thrombosis (DVT) during an
outpatient or emergency room (ER) visit after November 2, 2012, and who were
treated with rivaroxaban or LMWH/warfarin on the same day, were identified.
Patients were observed over 1, 2, 3, and 4 weeks after the DVT diagnosis. The
mean numbers of hospitalizations for all causes and for venous thromboembolism
(VTE) (which included those for DVT or pulmonary embolism), as well as other
health care resource utilization (ER, outpatient, and other visits), and the
associated health care costs and pharmacy costs, were evaluated and compared
between cohorts using the Lin method. FINDINGS: All of the 512 rivaroxaban
treated patients were well matched with the LMWH/warfarin-treated patients. The
mean numbers of all-cause hospitalizations were significantly lower in the
rivaroxaban users compared with those in the LMWH/warfarin users over 1 week
(0.012 vs 0.032; P = 0.044) and 2 weeks (0.022 vs 0.048; P = 0.040). The
corresponding mean numbers of VTE-related hospitalizations were significantly
lower with rivaroxaban over 1 week (0.008 vs 0.028; P = 0.020), 2 weeks (0.016 vs
0.042; P = 0.020), and 4 weeks (0.034 vs 0.068; P = 0.036). The mean numbers of
all-cause and VTE-related outpatient visits were also significantly lower in
rivaroxaban users compared with those in LMWH/warfarin users over 1, 2, 3, and 4
weeks (all, P < 0.001). In terms of all-cause and VTE-related ER and other
visits, no statistically significant differences were found between cohorts over
the first 4 weeks. The associated mean all-cause total health care costs were
significantly lower in the rivaroxaban users compared with those in the
LMWH/warfarin users over 1 week (US $2332 vs $3428; P < 0.001) and 2 weeks ($3108
vs $4524; P < 0.001); moreover, significantly lower mean costs related to all
cause hospitalizations (weeks 1 and 2) and pharmacy (weeks 1-4) were observed in
patients treated with rivaroxaban, while no differences were found in costs
related to ER visits (weeks 1-4), outpatient visits (weeks 1-4), or other visits
(with the exception of week 1). IMPLICATIONS: Patients with DVT treated with
rivaroxaban after an outpatient/ER visit had significantly lower mean numbers of
hospitalizations and outpatient visits, as well as lower mean total,
hospitalization, and pharmacy costs during the first 2 weeks of treatment
compared with those in matched LMWH/warfarin users.
PMID- 27491279
TI - Demographic and Clinical Characteristics of Patients With Type 2 Diabetes
Mellitus Initiating Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Study of
UK General Practice.
AB - PURPOSE: The majority of people with type 2 diabetes mellitus (T2DM) will develop
chronic kidney disease in their lifetime. Because most dipeptidyl peptidase (DPP)
4 inhibitors require dose adjustment in patients with T2DM and renal impairment,
we aimed to understand how these treatments are prescribed in UK clinical
practice, and to determine whether recommended dose adjustments are being made at
initial prescription. METHODS: This retrospective, descriptive cohort study
analyzed data from the Clinical Practice Research Datalink (CPRD). Patients of
interest were those with T2DM and renal impairment initiated on a DPP-4 inhibitor
between 2014 and 2015. Patients under 40 years of age and with type 1 diabetes
were excluded. Descriptive statistics were calculated for baseline demographic
and clinical characteristics, and the study protocol was approved by the
Independent Scientific Advisory Committee for Medicines and Healthcare products
Regulatory Agency database research. FINDINGS: A total of 3425 patients diagnosed
with T2DM and renal impairment and initiated on a DPP-4 inhibitor were
identified. The percentages of patients prescribed the high dose of saxagliptin,
alogliptin,sitagliptin, and vildagliptin were 48%, 43%, 41%, and 27%,
respectively, which is not recommended given their renal dysfunction. These are
conservative estimates, as they do not include patients with severe renal
impairment on sitagliptin and alogliptin, whose doses should be further reduced.
No patients were prescribed an inappropriately high dose of linagliptin, as there
is no requirement for dose adjustment in patients with renal impairment.
IMPLICATIONS: In this study, a considerable number of patients with T2DM and
renal impairment were prescribed an inappropriately high dose of saxagliptin,
alogliptin, sitagliptin, or vildagliptin for their level of renal impairment at
treatment initiation. This prescribing could have been due to the complexity of
different dosing requirements, or a lack of awareness of the need for dose
adjustment of most DPP-4 inhibitors in patients with renal impairment.
Linagliptin may be used in patients with moderate or severe renal impairment
without dose adjustment.
PMID- 27491280
TI - Lack of a Pharmacokinetic Interaction Between Saxagliptin and Dapagliflozin in
Healthy Subjects: A Randomized Crossover Study.
AB - PURPOSE: This single-dose, open-label, randomized, 3-period, 3-treatment
crossover drug-drug interaction study was conducted to evaluate differences in
the pharmacokinetic properties of saxagliptin and dapagliflozin when
coadministered. METHODS: Healthy subjects (N = 42) were randomized to receive
saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus
dapagliflozin 10 mg coadministered; there was a washout period of >=6 days
between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy
saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma
concentrations and pharmacokinetic parameters were collected before and up to 60
hours after the dose. No interaction was to be concluded if the 90% CIs for the
geometric mean ratios of the combination compared with each drug given alone for
Cmax and AUCinf were within 0.80 to 1.25. FINDINGS: The results indicated that
dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5
OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs
for Cmax and AUCinf for all comparisons were contained entirely within the 0.80
to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral
clearance or half-life) of saxagliptin or dapagliflozin were similar when each
medicine was administered alone or when coadministered. No safety profile or
tolerability findings of concern were observed during the study. All adverse
events were mild, and no serious adverse events were reported. IMPLICATIONS:
These data indicate that coadministration of saxagliptin and dapagliflozin
exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov
identifier: NCT01662999.
PMID- 27491281
TI - Superbugs, Colistin, and Related Issues.
PMID- 27491282
TI - Prescribing Patterns of Oral Antineoplastic Therapies Observed in the Treatment
of Patients With Advanced Prostate Cancer Between 2012 and 2014: Results of an
Oncology EMR Analysis.
AB - PURPOSE: The purpose of this study was to examine, using a US electronic medical
records (EMR) database, the clinical characteristics and real-world treatment
sequences in men with advanced prostate cancer who initiated treatment with
abiraterone acetate or enzalutamide. METHODS: This retrospective, observational
study evaluated adult male patients with a diagnosis of prostate cancer
(International Classification of Diseases, Ninth Revision, Clinical Modification
code 185) in the EMR database between July 1, 2011, and March 31, 2014, who had
initiated first-line treatment with abiraterone acetate or enzalutamide between
September 1, 2012, and March 31, 2014. The first record for a patient initiating
abiraterone acetate or enzalutamide was the index date. Patients had 6 months of
pre-index medical record history and a variable length follow-up period,
extending from the index date to the end of medical record data availability or
date of the end of the study (March 31, 2014). The sequence of first- and second
line therapies for advanced prostate cancer therapy was reported. FINDINGS: A
total of 809 patients met study inclusion and exclusion criteria. This study
found that the majority of patients who initiated treatment with either
abiraterone acetate or enzalutamide between September 1, 2012, and March 31,
2014, received a single line of therapy (72%); abiraterone acetate was the most
common first-line treatment (74% of first-line patients). A subset of patients
treated first-line with either abiraterone acetate or enzalutamide were
transitioned to an oral second-line agent (17% of first-line abiraterone acetate
treated patients transitioned to second-line enzalutamide, and 16% of first-line
enzalutamide-treated patients transitioned to second-line abiraterone acetate).
Chemotherapy with docetaxel was also a commonly observed second-line treatment
selection, occurring in 8% of first-line abiraterone acetate-treated patients and
in 7% of first-line enzalutamide-treated patients. IMPLICATIONS: This EMR study
is among the first to present evidence of US physician practice prescribing
patterns regarding initiation of oral antineoplastic agents and use of subsequent
therapies in patients with advanced prostate cancer.
PMID- 27491283
TI - Integrative Review: Delivery of Healthcare Services to Adolescents and Young
Adults During and After Foster Care.
AB - The purpose of this integrative review is to summarize evidence describing
delivery of healthcare services to adolescents while in foster care and to young
adults after they exit foster care. The long-term, deleterious effect of abuse
and/or neglect by caregivers among youth who have been placed in foster care is
grounded in empirical evidence demonstrating the relationship between long-term
health needs and exposure to trauma in childhood. Evidence is needed to provide
culturally-specific care and also to identify knowledge gaps in the care of
adolescents and young adults who have been in the foster care system. Peer
reviewed research studies published between 2004 and 2014 that include samples of
youth 12 to 30 years of age are included in the review. Eighteen studies met
inclusion criteria for the review. Physical and behavioral healthcare needs among
youth with foster care experience are significant. The ability to adequately meet
health needs are inextricable from the ability to negotiate resources and to
successfully interact with adults. Challenges that youth with foster care
histories experience when transitioning into young adulthood are comparable to
other populations of vulnerable youth not in foster care. Nurses must use each
healthcare encounter to assess how the social determinants of health facilitate
or impede optimal health among youth with foster care experience. The development
of integrated intervention strategies to inform best practice models is a
priority for current and former foster care youth as they transition into young
adulthood.
PMID- 27491284
TI - Squamous cell carcinoma in chronic osteomyelitis: a case report and review of the
literature.
AB - BACKGROUND: Chronic osteomyelitis is a challenging problem, and malignant
transformation is a rare occurrence. We report a case of a patient with squamous
cell carcinoma arising from an osteomyelitic hotbed and discuss through a
literature review the etiopathogenesis, diagnosis, and treatment of this lesion.
CASE PRESENTATION: A 69-year-old Italian man had sustained an exposed tibial
fracture 40 years ago during a road accident, for which he had undergone various
surgical osteosynthesis treatments with multiple antibiotic therapies. He
presented to our hospital because of recurrence of a fistula at the proximal
third of the anterior region of the tibia. For 2 months, we treated the lesion
with antibiotics, and local medication with curettage. We saw no evidence of
lesion improvement, and we advised the patient to undergo a knee amputation,
which he refused. The alternative we chose was a surgical toilet of the
osteomyelitic hotbed and used bioglass as a bone substitute. After 2 months of
follow-up, we noticed a fulminating, budding formation in the area of the
surgical wound that turned out to be a squamous cell carcinoma on biopsy. The
patient again refused the amputation and underwent a wide-margin surgical
debridement. After 2 months, the carcinoma recurred, and an above-the-knee
amputation was performed. CONCLUSIONS: Our experience with this case indicates
that amputation is the most appropriate treatment for squamous carcinoma
occurring in patients with chronic osteomyelitis. To avoid risks of lymphonodular
and organ metastasization, this radical surgical procedure should not be delayed.
Early diagnosis and timely therapy can prevent amputation only in selected cases.
Surgeons who treat osteomyelitis and chronic wounds should be aware of the risk
of tumor degeneration. Squamous cell carcinoma associated with chronic
osteomyelitis has a low-grade malignancy, but implications of lymphonodular
involvement and organ metastasis should not be excluded.
PMID- 27491286
TI - Influence of bisphosphonate therapy on bone geometry, volumetric bone density and
bone strength of femoral shaft in postmenopausal women with rheumatoid arthritis.
AB - BACKGROUND: There is evidence that postmenopausal women with rheumatoid arthritis
(RA) on glucocorticoid (GC) therapy and bisphosphonate (BP) have an increased
risk for atypical subtrochanteric and atypical diaphyseal femoral fracture (AFF).
The underlying mechanism has not been elucidated so far. Using peripheral
quantitative computed tomography (pQCT), the aim of the present study was to
compare bone geometry, volumetric bone mineral density (vBMD) and bone strength
of femoral shaft in BP-treated and BP-naive postmenopausal women with RA.
METHODS: Prospective cross-sectional pQCT scans were taken at 33 % of total femur
of BP-treated and BP-naive RA patients. Bone parameters of the two groups were
compared and correlated to disease characteristics and muscle cross-sectional
area (CSA). RESULTS: A total of 60 consecutive postmenopausal RA patients, 20
with BP therapy and 40 BP-naive, were included in the study. The median age of
the subjects was 63.5 years (range 48-85 years), and median disease duration (RA)
was 12.0 years (range 2-47 years). Height and weight of the patients of the two
groups were comparable. Women in the BP group were on average 4.3 years older (p
= 0.044), and duration since menopause was on average 5.76 years longer (p =
0.045). In the BP group, there was a 13.31 % reduced muscle cross-sectional area
around the proximal thigh (p = 0.013); cortical CSA was smaller by 5.3 % (p =
0.043); however, total and medullary CSA, as well as cortical vBMD and the polar
bone stress-strain index of the femoral shaft were similar in the two groups. In
regression analysis, age, time since menopause and muscular CSA were significant
factors determining cortical CSA, cortical thickness and femoral index (p <
0.05). Regression model showed no significant effect of BP therapy on bone
geometry and density of the femoral diaphysis at 33 %. CONCLUSION: Differences in
cortical CSA between BP-treated and BP-naive postmenopausal RA patients were
found to be associated only with differences in age, time since menopause and
muscle cross-sectional area around the proximal thigh. In interpreting our
results, it should be kept in mind that BP was given only to patients with
increased fracture risk. This fact might have a confounding effect on our
findings of differences between the two groups.
PMID- 27491287
TI - Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in
chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's
lymphoma patients under Taiwan's national health insurance system.
AB - RATIONALE, AIM AND OBJECTIVE: The beneficial effects of granulocyte colony
stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy
induced febrile neutropenia (CIFN) were well documented throughout the
literature. However, existing data regarding its cost-effectiveness were
conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN
under Taiwan's National Health Insurance (NHI) system. METHODS: Data on clinical
outcomes and direct medical costs were derived for 5179 newly diagnosed breast
cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims
database. Patients were further categorized into three subgroups as "primary-",
"secondary-" and "no -" prophylaxis based on their patterns of G-CSF use.
Generalized estimating equations were applied to estimate the impact of G-CSF use
on the incidence of CIFN. The incremental cost-effectiveness ratios of primary
and secondary prophylactic G-CSF use were calculated and sensitivity analyses
were performed. RESULTS: Primary prophylaxis of G-CSF decreased the incidence of
CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer
and NHL patients, respectively. Compared with those with no prophylaxis, the
incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among
patients with breast cancer and NHL, respectively. In contrast, secondary
prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer
patients. CONCLUSION: Primary but not secondary prophylactic use of G-CSF was
cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI
system.
PMID- 27491285
TI - S6Ks isoforms contribute to viability, migration, docetaxel resistance and tumor
formation of prostate cancer cells.
AB - BACKGROUND: The S6 Kinase (S6K) proteins are some of the main downstream
effectors of the mammalian Target Of Rapamycin (mTOR) and act as key regulators
of protein synthesis and cell growth. S6K is overexpressed in a variety of human
tumors and is correlated to poor prognosis in prostate cancer. Due to the current
urgency to identify factors involved in prostate cancer progression, we aimed to
reveal the cellular functions of three S6K isoforms-p70-S6K1, p85-S6K1 and p54
S6K2-in prostate cancer, as well as their potential as therapeutic targets.
METHODS: In this study we performed S6K knockdown and overexpression and
investigated its role in prostate cancer cell proliferation, colony formation,
viability, migration and resistance to docetaxel treatment. In addition, we
measured tumor growth in Nude mice injected with PC3 cells overexpressing S6K
isoforms and tested the efficacy of a new available S6K1 inhibitor in vitro.
RESULTS: S6Ks overexpression enhanced PC3-luc cell line viability, migration,
resistance to docetaxel and tumor formation in Nude mice. Only S6K2 knockdown
rendered prostate cancer cells more sensitive to docetaxel. S6K1 inhibitor PF
4708671 was particularly effective for reducing migration and proliferation of
PC3 cell line. CONCLUSIONS: These findings demonstrate that S6Ks play an
important role in prostate cancer progression, enhancing cell viability,
migration and chemotherapy resistance, and place both S6K1 and S6K2 as a
potential targets in advanced prostate cancer. We also provide evidence that S6K1
inhibitor PF-4708671 may be considered as a potential drug for prostate cancer
treatment.
PMID- 27491288
TI - MAHILA: a protocol for evaluating a nurse-delivered mHealth intervention for
women with HIV and psychosocial risk factors in India.
AB - BACKGROUND: Women living with HIV are vulnerable to a variety of psychosocial
barriers that limit access and adherence to treatment. There is little evidence
supporting interventions for improving access and treatment adherence among
vulnerable groups of women in low- and middle-income countries. The M obile Phone
Based A pproach for H ealth I mprovement, L iteracy and A dherence (MAHILA) trial
is assessing the feasibility, acceptability and preliminary efficacy of a novel,
theory-guided mobile health intervention delivered by nurses for enhancing self
care and treatment adherence among HIV-infected women in India. METHODS/DESIGN:
Women (n = 120) with HIV infection who screen positive for depressive symptoms
and/or other psychosocial vulnerabilities are randomly assigned in equal numbers
to one of two treatment arms: treatment as usual plus the mobile phone
intervention (experimental group) or treatment as usual (control group). In
addition to treatment as usual, the experimental group receives nurse-delivered
self-care counselling via mobile phone at fixed intervals over 16 weeks. Outcome
measures are collected at baseline and at 4, 12, 24 and 36 weeks post-baseline.
Outcomes include antiretroviral treatment adherence, HIV-1 RNA, depressive
symptoms, illness perceptions, internalized stigma and quality of life.
DISCUSSION: The MAHILA trial will provide information about how a mobile health
counselling intervention delivered by non specialist nurses may improve access to
care and support the adherence and clinical outcomes of women with HIV infection
living in low- and middle-income countries such as India. TRIAL REGISTRATION:
NCT02319330 (First received: July 30, 2014; Last verified: January 2016).
PMID- 27491289
TI - Phylogeny of tick-derived Crimean-Congo hemorrhagic fever virus strains in Iran.
AB - The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was
assessed by collecting ticks from Golpayegan, Isfahan Province. Real time RT-PCR
was used to detect the CCHFV RNA in the tick population and the origins of the
viral sequences were determined. The CCHFV RNA was detected in 5.2% of 492 ticks
collected from livestock in different regions of Golpayegan. The tick species
that tested positive for the presence of CCHFV RNA included Hyalomma,
Rhipicephalus and Haemaphysalis species. Phylogenetic analysis using the partial
S-segment indicated that eight sequences clustered in clade IV (Asia-1) and three
other sequences aligned within clade VI (Europe) with other CCHFV strains from
Kosovo (Kosova1917) and Russia (Kashmanov).
PMID- 27491290
TI - Erratum to "A review of reverse vaccinology approaches for the development of
vaccines against ticks and tick borne diseases" [Ticks Tick-borne Dis. 7 (4)
(2016) 573-585].
PMID- 27491291
TI - Primary pure spindle cell carcinoma (sarcomatoid carcinoma) of the ovary: A case
report with immunohistochemical study.
AB - BACKGROUND: In the ovary, sarcomatoid carcinoma has been reported only as mural
nodules in epithelial malignant or borderline serous or mucinous cystic
neoplasms, and in teratomas. In this paper we report a rare case of a solid
sarcomatoid carcinoma of the ovary, without accompanying component of giant
cells, pleomorphic cells, or glandular and other epithelial structures. CASE
PRESENTATION: This case report refers to a sarcomatoid carcinoma of the ovary in
in a 57 year-old woman with abdominal pain. Macroscopically, the neoplasm was a
15x10x5 cm ovarian mass that featured gray white solid fleshy areas, interspersed
with areas of necrosis, hemorrhage and cystic spaces filled with thick fluid. The
epithelial differentiation of the tumor was demonstrated by strong and diffuse
reactivity to CAM5.2 and focal immunoreactivity to EMA. A diagnosis of malignant
mesenchymal tumor was excluded due to negativity for desmin, smooth muscle actin,
caldesmon, CD34, CD10, and myoglobin. Neural, neuroendocrine neoplasm, melanoma
and Perivascular Epithelioid Cell Tumor (PEComa) were excluded because of
negativity for S100, chromogranin, synaptophysin and HMB45. CONCLUSION: Primary
ovarian spindle cell carcinoma is a rare neoplasm, which must be considered in
the differential diagnosis of solid ovarian mass with spindle cell appearance.
This case adds to our knowledge of the biological behavior of these rare
neoplasms. The distinction from true sarcomas and carcinosarcomas is important
because of the more favorable prognosis of the spindle cell carcinomas. However
their diagnosis necessitates a careful tissue sampling and immunohistochemical
staining.
PMID- 27491292
TI - Short sleep duration is associated with increased risk of pre-hypertension and
hypertension in Chinese early middle-aged females.
AB - PURPOSE: The aim of this study is to investigate the relationship between sleep
duration and hypertension in a middle-aged Chinese population. METHODS: Cross
sectional data of 20,505 individuals aged 35-64 years from Taizhou longitudinal
study was used. Logistic regression models were used to calculate odds ratios
(ORs) for the risk of pre-hypertension and hypertension in association with sleep
duration. RESULTS: Short sleep duration was associated with high systolic and
diastolic blood pressure in comparison with sleep duration of 7-8 h in females.
Short sleep duration was also associated with an increased risk of hypertension
in females. Age-stratified analysis showed that as compared with sleep duration
of 7-8 h, sleep duration <6 h increased risk of hypertension after controlling
for multiple covariates with an OR of 1.766 (1.024-2.775) in early middle-aged
females of 35-44 years. More importantly, sleeping less than 6 h is associated
with increased risk of pre-hypertension in females of this age category, after
controlling for multiple covariates with an OR of 1.769 (1.058-2.958).
CONCLUSIONS: Sleeping less than 6 h a day is associated with increased risk of
pre-hypertension and hypertension in Chinese early middle-aged females. The high
risk populations require sufficient sleep, which could probably prevent the
increased risk of pre-hypertension as well as hypertension.
PMID- 27491293
TI - A Pilot Study on Telephone Cognitive Behavioral Therapy for Patients Six-Months
Post-Bariatric Surgery.
AB - OBJECTIVE: This study aimed to determine the feasibility and preliminary efficacy
of a post-operative telephone-based cognitive behavioral therapy intervention
(Tele-CBT) in improving eating pathology and psychosocial functioning. METHODS:
Six-month post-operative bariatric surgery patients (n = 19) received six
sessions of Tele-CBT. Study outcome variables included binge eating (BES),
emotional eating (EES), depressive symptoms (PHQ-9), and anxiety symptoms (GAD
7). RESULTS: Retention was 73.7 % post-intervention. Tele-CBT resulted in
significant reductions in mean difference scores on BES, EES-Total, EES-Anxiety,
EES-Anger, PHQ9, and GAD7. Tele-CBT patients experienced a mean weight loss of
8.62 +/- 15.02 kg between 6-months post-surgery (pre-Tele-CBT) and 12-months post
surgery. CONCLUSIONS: These preliminary results suggest that post-surgery Tele
CBT is feasible and can improve post-surgery symptoms of psychopathology in this
uncontrolled study, supporting the need for a randomized controlled trial.
PMID- 27491294
TI - Micronutrient Status in Morbidly Obese Patients Prior to Laparoscopic Sleeve
Gastrectomy and Micronutrient Changes 5 years Post-surgery.
AB - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become more popular in
recent years. The aim of this study was to determine the vitamin and mineral
status in patients up to 5 years after LSG and to explore changes that occurred
from pre-operatively to 1, 2 and 5 years after surgery. METHODS: Data reviewed
included age, sex, weight and body mass index (BMI), micronutrient supplements
consumed and blood levels of 25 hydroxyvitamin D (25 (OH) D), PTH (parathyroid
hormone), ferritin, haemoglobin, folate and vitamin B12, prior to and post-LSG.
Data was collated from medical records of morbidly obese patients who had
undergone LSG surgery. RESULTS: There were a maximum of 336 patients with pre
operative and 1 year after surgery values, n = 272 for 2 years and n = 116 for 5
years after surgery. At 5 years, only 54 % (58/107) of patients reported taking
daily multivitamin supplements. Whilst most patients had values within the
reference range for haemoglobin, vitamin B12, folate and vitamin D 5 years after
LSG, 36 % (34/94) of the patients had serum ferritin below reference value.
CONCLUSION: This study has highlighted a low micronutrient supplementation
adherence. Ferritin levels decreased over time even with multivitamin
supplementation. To improve micronutrient guidelines prior to and after LSG, more
research, including controlled supplementation studies, are necessary.
PMID- 27491295
TI - Reactive oxygen species in organ-specific autoimmunity.
AB - Reactive oxygen species (ROS) have been extensively studied in the induction of
inflammation and tissue damage, especially as it relates to aging. In more recent
years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here,
ROS accumulation leads to apoptosis and autoantigen structural changes that
result in novel specificities. ROS have been implicated not only in the
initiation of the autoimmune response but also in its amplification and spreading
to novel epitopes, through the unmasking of cryptic determinants. This review
will examine the contribution of ROS to the pathogenesis of four organ specific
autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple
sclerosis, and vitiligo), and compare it to that of a better characterized
systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco
smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant
properties, thus capable of differentially modulating the autoimmune response.
PMID- 27491298
TI - N-linked glycosite profiling and use of Skyline as a platform for
characterization and relative quantification of glycans in differentiating xylem
of Populus trichocarpa.
AB - Our greater understanding of the importance of N-linked glycosylation in
biological systems has spawned the field of glycomics and development of
analytical tools to address the many challenges regarding our ability to
characterize and quantify this complex and important modification as it relates
to biological function. One of the unmet needs of the field remains a systematic
method for characterization of glycans in new biological systems. This study
presents a novel workflow for identification of glycans using Individuality
Normalization when Labeling with Isotopic Glycan Hydrazide Tags (INLIGHTTM)
strategy developed in our lab. This consists of monoisotopic mass extraction
followed by peak pair identification of tagged glycans from a theoretical library
using an in-house program. Identification and relative quantification could then
be performed using the freely available bioinformatics tool Skyline. These
studies were performed in the biological context of studying the N-linked glycome
of differentiating xylem of the poplar tree, a widely studied model woody plant,
particularly with respect to understanding lignin biosynthesis during wood
formation. Through our workflow, we were able to identify 502 glycosylated
proteins including 12 monolignol enzymes and 1 peroxidase (PO) through
deamidation glycosite analysis. Finally, our novel semi-automated workflow
allowed for rapid identification of 27 glycans by intact mass and by NAT/SIL peak
pairing from a library containing 1573 potential glycans, eliminating the need
for extensive manual analysis. Implementing Skyline for relative glycan
quantification allowed for improved accuracy and precision of quantitative
measurements over current processing tools which we attribute to superior
algorithms correction for baseline variation and MS1 peak filtering. Graphical
abstract Workflow for FANGS-INLIGHT glycosite profiling of plant xylem and
monolignol proteins followed by INLIGHT tagging with semi-automated
identification of glycans by light-heavy peak pairs. Finally, manual validation
and relative quantification was performed in Skyline.
PMID- 27491297
TI - Environmental factors in autoimmune diseases and their role in multiple
sclerosis.
AB - An increase in autoimmune diseases poses a socioeconomic challenge worldwide.
Predisposing genetic risk has been identified, yet environmental factors make up
a significant part of the risk in disease initiation and propagation. Next to
improved hygiene and a gross reduction of infections, changes in dietary habits
are one of the most evident Western lifestyle factors potentially associated with
the increase in autoimmune diseases. Growing evidence suggests that particularly
a typical 'Western diet', rich in saturated fat and salt and related pathologies
can have a profound impact on local and systemic immune responses under
physiologic and autoimmune conditions such as in multiple sclerosis (MS). In this
review, we discuss recent findings on environmental factors influencing
autoimmunity with an emphasis on the impact of 'Western diet' on immune
homeostasis and gut microbiota in MS.
PMID- 27491299
TI - Raman spectroscopy as a process analytical technology for pharmaceutical
manufacturing and bioprocessing.
AB - Adoption of Quality by Design (QbD) principles, regulatory support of QbD,
process analytical technology (PAT), and continuous manufacturing are major
factors effecting new approaches to pharmaceutical manufacturing and
bioprocessing. In this review, we highlight new technology developments, data
analysis models, and applications of Raman spectroscopy, which have expanded the
scope of Raman spectroscopy as a process analytical technology. Emerging
technologies such as transmission and enhanced reflection Raman, and new
approaches to using available technologies, expand the scope of Raman
spectroscopy in pharmaceutical manufacturing, and now Raman spectroscopy is
successfully integrated into real-time release testing, continuous manufacturing,
and statistical process control. Since the last major review of Raman as a
pharmaceutical PAT in 2010, many new Raman applications in bioprocessing have
emerged. Exciting reports of in situ Raman spectroscopy in bioprocesses
complement a growing scientific field of biological and biomedical Raman
spectroscopy. Raman spectroscopy has made a positive impact as a process
analytical and control tool for pharmaceutical manufacturing and bioprocessing,
with demonstrated scientific and financial benefits throughout a product's
lifecycle.
PMID- 27491296
TI - BET bromodomain proteins and epigenetic regulation of inflammation: implications
for type 2 diabetes and breast cancer.
AB - Chronic inflammation drives pathologies associated with type 2 diabetes (T2D) and
breast cancer. Obesity-driven inflammation may explain increased risk and
mortality of breast cancer with T2D reported in the epidemiology literature.
Therapeutic approaches to target inflammation in both T2D and cancer have so far
fallen short of the expected improvements in disease pathogenesis or outcomes.
The targeting of epigenetic regulators of cytokine transcription and cytokine
signaling offers one promising, untapped approach to treating diseases driven by
inflammation. Recent work has deeply implicated the Bromodomain and Extra
Terminal domain (BET) proteins, which are acetylated histone "readers", in
epigenetic regulation of inflammation. This review focuses on inflammation
associated with T2D and breast cancer, and the possibility of targeting BET
proteins as an approach to regulating inflammation in the clinic. Understanding
inflammation in the context of BET protein regulation may provide a basis for
designing promising therapeutics for T2D and breast cancer.
PMID- 27491300
TI - An interface for online coupling capillary electrophoresis to dielectric barrier
discharge ionization mass spectrometry.
AB - The online combination of capillary electrophoresis (CE) with mass spectrometry
(MS) has long been desired for the capability of direct and simultaneous
separation and detection with high efficiency, accuracy, and throughput. In this
work, a novel CE-MS interface was developed, using dielectric barrier discharge
ionization (DBDI). The interface employed a spray tip with a coaxial three-layer
structure, into which the CE sample solution, the sheath liquid, and the
nebulizing gas were introduced. The spray tip was put between the DBDI outlet and
the MS inlet, thus the CE sample solution could be blended with the sheath
liquid, then nebulized. The nebulized sample could be ionized by DBDI, and
finally analyzed by MS. The key parameters of the interface were optimized. Then,
proof-of-concept experiments separating and detecting the mixture of
metronidazole and acetaminophen solutions were conducted. The results showed high
separation efficiency, low time consumption, high reproducibility, and
convenience in operation. In addition, the interface exhibited a high tolerance
of non-volatile salts and surfactants, which would be widely used in CE analyses.
All of these results demonstrated that the newly developed CE-DBDI-MS interface
could be successfully used in CE-MS studies, and could be further utilized in
multiple areas involving efficient separation and detection.
PMID- 27491301
TI - Novel diffusive gradients in thin films technique to assess labile sulfate in
soil.
AB - A novel diffusive gradients in thin films (DGT) technique for sampling labile
soil sulfate was developed, based on a strong basic anion exchange resin
(Amberlite IRA-400) for sulfate immobilization on the binding gel. For reducing
the sulfate background on the resin gels, photopolymerization was applied instead
of ammonium persulfate-induced polymerization. Agarose cross-linked
polyacrylamide (APA) hydrogels were used as diffusive layer. The sulfate
diffusion coefficient in APA gel was determined as 9.83 * 10(-6) +/- 0.35 * 10(
6) cm(2) s(-1) at 25 degrees C. The accumulated sulfate was eluted in 1 mol L(
1) HNO3 with a recovery of 90.9 +/- 1.6 %. The developed method was tested
against two standard extraction methods for soil sulfate measurement. The
obtained low correlation coefficients indicate that DGT and conventional soil
test methods assess differential soil sulfate pools, rendering DGT a potentially
important tool for measuring labile soil sulfate.
PMID- 27491304
TI - EPR-correlated dipolar spectroscopy by Q-band chirp SIFTER.
AB - While two-dimensional correlation spectra contain more information as compared to
one-dimensional spectra, typical spectral widths encountered in electron
paramagnetic resonance (EPR) spectroscopy largely restrict the applicability of
correlation techniques. In essence, the monochromatic excitation pulses
established in pulsed EPR often cannot uniformly excite the entire spectrum.
Here, this restriction is alleviated for nitroxide spin labels at Q-band
microwave frequencies around 35 GHz. This is achieved by substitution of
monochromatic pulses by frequency-swept chirp pulses tailored for uniform
excitation. Unwanted interference effects brought by this substitution are
analyzed for a pair of electron spins with secular dipolar coupling.
Experimentally, the dipole-dipole interaction can be separated from other
interactions by a constant-time Zeeman-compensated solid echo sequence called
SIFTER. Such SIFTER experiments usually yield a one-dimensional dipolar spectrum.
EPR-correlated dipolar spectra can be obtained when the four pulses are replaced
by chirp pulses. These two-dimensional spectra encode additional information on
the geometrical arrangement of the two spin labels. With the excitation
parameters achieved by a home-built Q-band spectrometer capable of frequency
swept excitation, unwanted interference effects can be largely neglected for the
examined model compound with a spin-spin distance of 4 nm. The experimentally
obtained correlation pattern conforms to the expectation based on the inter-spin
geometry of the investigated rigid model compound.
PMID- 27491303
TI - Effects of physical therapy and relaxation techniques on the parameters of pain
in university students with tension-type headache: A randomised controlled
clinical trial.
AB - INTRODUCTION: Non-pharmacological treatments help control tension-type headache;
however, evidence about their effectiveness is still limited. This study
evaluates the effectiveness of physical therapy based on cervical spine
kinesiotherapy and posture correction exercises compared to a programme of
relaxation techniques only (Schultz's Autogenic Training, AT). METHODS: Tension
type headache is very common among university students. We randomly selected 152
university students with a diagnosis of tension-type headache according to the
criteria of the International Headache Society. Eighty-four were women (55.3%)
and 68 were men (44.7%). Mean age was 20.42+/-2.36 years. The study design is a
randomised controlled trial of a non-pharmacological intervention with a blinded
evaluation of response variables. We compared the results of two independent
samples: AT was used in one of the groups while the other group received AT plus
cervical spine kinesiotherapy and posture correction training. Patients recorded
any changes in the parameters of pain (frequency, intensity, and duration) and
drug consumption in a headache diary before treatment, at 4 weeks, and at 3
months. RESULTS: Both interventions achieved a decrease in all the parameters of
pain; however, decreases in frequency and intensity were more significant in the
combined treatment group (P<0.01) (d=0.4). CONCLUSIONS: Such active, non-invasive
therapies as AT and cervical spine kinesiotherapy, and especially the combination
of both, effectively reduce tension-type headache by preventing and managing the
potential psychophysical causes of this disorder. Future research should aim to
assess the long-term effects of these interventions.
PMID- 27491302
TI - Quantitative patterns of Hsps in tubular adenoma compared with normal and tumor
tissues reveal the value of Hsp10 and Hsp60 in early diagnosis of large bowel
cancer.
AB - Large bowel carcinogenesis involves accumulation of genetic alterations leading
to transformation of normal mucosa into dysplasia and, lastly, adenocarcinoma. It
is pertinent to elucidate the molecular changes occurring in the pre-neoplastic
lesions to facilitate early diagnosis and treatment. Heat shock proteins (Hsps),
many of which are molecular chaperones, are implicated in carcinogenesis, and
their variations with tumor progression encourage their study as biomarkers.
There are many reports on Hsps and cancer but none to our knowledge on their
systematic quantification in pre-neoplastic lesions of the large bowel. We
performed immunohistochemical determinations of Hsp10, Hsp60, Hsp70, and Hsp90 in
biopsies of large bowel tubular adenomas with moderate grade of dysplasia and
compared to normal mucosa and adenocarcinoma with a moderate grade of
differentiation (G2). A significant elevation of Hsp10 and Hsp60 only, i.e., in
the absence of elevation of Hsp70 or Hsp90, in both epithelium and lamina propria
was found in tubular adenoma by comparison with normal mucosa. In contrast,
adenocarcinoma was characterized by the highest levels of Hsp10 and Hsp60 in
epithelium and lamina propria, accompanied by the highest levels of Hsp70 only in
epithelium and of Hsp90 only in lamina propria, by comparison with normal and
tubular adenoma counterparts. Hsp10 and Hsp60 are promising biomarkers for early
diagnosis of tubular adenoma and for its differentiation from more advanced
malignant lesions. Hsp10 and Hsp60 may be implicated in carcinogenesis from its
very early steps and, thus, are potentially convenient targets for therapy.
PMID- 27491305
TI - Immigrants as Research Partners: A Review of Immigrants in Community-Based
Participatory Research (CBPR).
AB - Community-based participatory research (CBPR) is uniquely suited to engage
immigrants in all aspects of research, from research question development to data
collection to interpretation and dissemination of results. An increasing number
of research studies have utilized the methodology for exploring complex health
issues for immigrants. In the current manuscript, we present a review of peer
reviewed articles in health-related research where CBPR was conducted in
partnership with immigrants. We examined the role of immigrants in the CBPR
process and how immigrant involvement improved/enhanced the research rigor. A
total of 161 articles met the inclusion criteria. The results of this literature
review enhance our understanding of how CBPR can be used in direct collaboration
with immigrants and highlights the many potential benefits for both researchers
and immigrant communities.
PMID- 27491306
TI - Proteomic Profiling and the Predicted Interactome of Host Proteins in Compatible
and Incompatible Interactions Between Soybean and Fusarium virguliforme.
AB - Sudden death syndrome (SDS) is a complex of two diseases of soybean (Glycine
max), caused by the soil borne pathogenic fungus Fusarium virguliforme. The root
rot and leaf scorch diseases both result in significant yield losses worldwide.
Partial SDS resistance has been demonstrated in multiple soybean cultivars. This
study aimed to highlight proteomic changes in soybean roots by identifying
proteins which are differentially expressed in near isogenic lines (NILs)
contrasting at the Rhg1/Rfs2 locus for partial resistance or susceptibility to
SDS. Two-dimensional gel electrophoresis resolved approximately 1000 spots on
each gel; 12 spots with a significant (P < 0.05) difference in abundance of 1.5
fold or more were picked, trypsin-digested, and analyzed using quadruple time-of
flight tandem mass spectrometry. Several spots contained more than one protein,
so that 18 distinct proteins were identified overall. A functional analysis
performed to categorize the proteins depicted that the major pathways altered by
fungal infection include disease resistance, stress tolerance, and metabolism.
This is the first report which identifies proteins whose abundances are altered
in response to fungal infection leading to SDS. The results provide valuable
information about SDS resistance in soybean plants, and plant partial resistance
responses in general. More importantly, several of the identified proteins could
be good candidates for the development of SDS-resistant soybean plants.
PMID- 27491307
TI - Application of active edible coatings made from basil seed gum and thymol for
quality maintenance of shrimp during cold storage.
AB - BACKGROUND: To improve the quality of Pacific white shrimp (Litopenaeus
vannamei), active coating solutions were prepared by dissolving 10 g L-1 of basil
seed gum (BSG) and adding various levels of thymol (6%, 8% and 10% w/w based on
gum weight) and glycerol (3.5 g L-1 ) as plasticizer. The effects of coating
solutions (CS1-4) on the quality changes of shrimps during refrigerated storage
over 20 days were investigated. RESULTS: The total volatile basic nitrogen (TVB
N) value in shrimps coated with CS4 (containing 10% w/w thymol) was slightly
higher than the upper threshold of 300 mg kg-1 on day 18, whereas that of
uncoated shrimps increased to, or over, the threshold value on day 7. Active
coatings significantly reduced (P < 0.05) microbial growth in shrimps during the
cold storage without a negative impact on the organoleptic properties. Using CS4
on the shrimp samples immediately reduced total viable count and psychrotrophic
bacteria count by 2 and 1 log colony forming units g-1 , respectively, compared
to controls. CONCLUSION: The results of the present study revealed that the
active edible coatings based on BSG activated with thymol had good potential to
be used in the production of active packaging for various food applications. (c)
2016 Society of Chemical Industry.
PMID- 27491308
TI - Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles.
AB - Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic
epithelium and presents with diverse phenotypes yet to be characterized
molecularly. High recurrence rates of 50-80% with conservative treatment in some
sub-types warrants radical surgical resections resulting in high morbidity. The
objective of the study was to characterize the transcriptome of ameloblastoma and
identify relevant genes and molecular pathways using normal odontogenic tissue
(human "dentome") for comparison. Laser capture microdissection was used to
obtain neoplastic epithelial tissue from 17 tumors which were examined using the
Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct
molecular clusters that were associated with pre-secretory ameloblast and
odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the
follicular type while 6/7 of the samples in the odontoblast cluster were of the
plexiform type (p < 0.05). Common pathways altered in both clusters included cell
cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer
driving genes such as TP53 and members of the MAPkinase pathways. The pre
secretory ameloblast cluster exhibited higher activation of inflammatory pathways
while the odontoblast cluster showed greater disturbances in transcription
regulators. Our results are suggestive of underlying inter-tumor molecular
heterogeneity of ameloblastoma sub-types and have implications for the use of
tailored treatment.
PMID- 27491310
TI - Intraocular foreign body removal: a novel technique using intraoperative imaging.
AB - We describe a case illustrating a new technique of using intraoperative optical
coherence tomography (IOCT) for foreign body removal from the limbus and cornea.
In this case, fragments of a fish hook in the temporal limbus and cornea were
identified on the OCT. The residual pieces were then removed, assisted by high
resolution, real-time cross-sectional imaging, IOCT. While this technique
involves steep learning curve, we believe that it is safe for the patient and
helps surgeon with instant decision making and reduce orbital manipulation.
PMID- 27491311
TI - John Garrow.
PMID- 27491312
TI - Glycosaminoglycans contribute to extracellular matrix fiber recruitment and
arterial wall mechanics.
AB - Elastic and collagen fibers are well known to be the major load-bearing
extracellular matrix (ECM) components of the arterial wall. Studies of the
structural components and mechanics of arterial ECM generally focus on elastin
and collagen fibers, and glycosaminoglycans (GAGs) are often neglected. Although
GAGs represent only a small component of the vessel wall ECM, they are
considerably important because of their diverse functionality and their role in
pathological processes. The goal of this study was to study the mechanical and
structural contributions of GAGs to the arterial wall. Biaxial tensile testing
was paired with multiphoton microscopic imaging of elastic and collagen fibers in
order to establish the structure-function relationships of porcine thoracic aorta
before and after enzymatic GAG removal. Removal of GAGs results in an earlier
transition point of the nonlinear stress-strain curves [Formula: see text].
However, stiffness was not significantly different after GAG removal treatment,
indicating earlier but not absolute stiffening. Multiphoton microscopy showed
that when GAGs are removed, the adventitial collagen fibers are straighter, and
both elastin and collagen fibers are recruited at lower levels of strain, in
agreement with the mechanical change. The amount of stress relaxation also
decreased in GAG-depleted arteries [Formula: see text]. These findings suggest
that the interaction between GAGs and other ECM constituents plays an important
role in the mechanics of the arterial wall, and GAGs should be considered in
addition to elastic and collagen fibers when studying arterial function.
PMID- 27491309
TI - Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other
catecholamine-related enzymes, and their human genes in relation to the drug and
gene therapies of Parkinson's disease (PD): historical overview and future
prospects.
AB - Tyrosine hydroxylase (TH), which was discovered at the National Institutes of
Health (NIH) in 1964, is a tetrahydrobiopterin (BH4)-requiring monooxygenase that
catalyzes the first and rate-limiting step in the biosynthesis of catecholamines
(CAs), such as dopamine, noradrenaline, and adrenaline. Since deficiencies of
dopamine and noradrenaline in the brain stem, caused by neurodegeneration of
dopamine and noradrenaline neurons, are mainly related to non-motor and motor
symptoms of Parkinson's disease (PD), we have studied human CA-synthesizing
enzymes [TH; BH4-related enzymes, especially GTP-cyclohydrolase I (GCH1);
aromatic L-amino acid decarboxylase (AADC); dopamine beta-hydroxylase (DBH); and
phenylethanolamine N-methyltransferase (PNMT)] and their genes in relation to PD
in postmortem brains from PD patients, patients with CA-related genetic diseases,
mice with genetically engineered CA neurons, and animal models of PD. We purified
all human CA-synthesizing enzymes, produced their antibodies for
immunohistochemistry and immunoassay, and cloned all human genes, especially the
human TH gene and the human gene for GCH1, which synthesizes BH4 as a cofactor of
TH. This review discusses the historical overview of TH, BH4-, and other CA
related enzymes and their genes in relation to the pathophysiology of PD, the
development of drugs, such as L-DOPA, and future prospects for drug and gene
therapy for PD, especially the potential of induced pluripotent stem (iPS) cells.
PMID- 27491314
TI - A self-reported survey on the confidence levels and motivation of New South Wales
practice nurses on conducting advance-care planning (ACP) initiatives in the
general-practice setting.
AB - Nurses are well positioned to initiate and conduct advance-care planning (ACP)
conversations; however, there has been limited research on practice nurses
performing this role in Australia. The aim of the present study was to understand
the beliefs, attitudes, perceptions, confidence, training and educational needs
of New South Wales practice nurses with regards to involvement in ACP. A cross
sectional online survey was conducted in August to October 2014. Nurses were
recruited through nursing organisations and Medicare Locals. There were 147
completed surveys (n=147). Participants were mostly female registered nurses,
with a median age of 50, and 6 years of practice-nurse experience. Practice
nurses were generally positive towards their involvement in ACP and believed it
would be beneficial for the community. Their confidence in initiating ACP
increased as their familiarity with patients increased. They showed a high level
of interest in participating in training and education in ACP. Barriers to their
involvement in ACP included the lack of a good documentation system, limited
patient-education resources and unclear source of remuneration. Nurses were also
concerned over legalities of ACP, ethical considerations and their understanding
of end-of-life care options. Nevertheless, they were highly receptive of
integrating ACP discussions and were willing to enhance their skills. These
findings uncover a need for further training and development of practice nurses
for ACP discussions.
PMID- 27491313
TI - Catechol-O-methyltransferase Val158Met polymorphism is associated with increased
risk of multiple uterine leiomyomas either positive or negative for MED12 exon 2
mutations.
AB - AIMS: To study the possible association of catechol-O-methyltransferase (COMT)
Val158Met polymorphism with multiple and solitary uterine leiomyomas (ULs) and to
check whether the COMT Val/Val genotype is associated with MED12 exon 2 mutations
in fibroids. METHODS: The COMT Val158Met allele and genotype frequencies were
compared between age-matched women with ULs (n=104) and controls (n=59). Patients
with UL were subcategorised by diagnosis of solitary (n=59) or multiple (n=45)
fibroids and by the presence of somatic MED12 exon 2 mutations in at least one
fibroid (n=32) or in neither fibroid (n=26). The association of COMT Val/Val
genotype with the presence of any ULs, solitary/multiple ULs and ULs
positive/negative for MED12 exon 2 mutations was evaluated by chi2 tests using a
dominant genotype model (G/G vs G/A+A/A) and expressed as ORs and 95% CIs.
RESULTS: The COMT Val/Val genotype frequency did not differ between the patients
with UL and the controls (28.8% vs 18.6%, p=0.149, OR 1.77; CI 0.81 to 3.86).
However, it was significantly higher in the patients who had multiple UL compared
with the solitary UL (40% vs 20.3%, p=0.028, OR 2.61; CI 1.09 to 6.24) and to the
controls (40% vs 18.6%, p=0.016, OR 2.91; CI 1.20 to 7.06). No association of the
COMT Val/Val genotype with UL-specific MED12 exon 2 mutations was found (p=0.662,
OR 0.77; CI 0.23 to 2.53). CONCLUSIONS: Women with COMT Val/Val genotype are at
high risk of developing multiple uterine fibroids either positive or negative for
MED12 exon 2 mutations. These data are important to design new strategies for UL
prophylaxis and treatment.
PMID- 27491315
TI - Prevalence of chronic kidney disease after preeclampsia.
AB - BACKGROUND: Preeclampsia (PE), an endothelial disease that affects kidney
function during pregnancy, is correlated to an increased future risk of
cardiovascular and chronic kidney disease. The Kidney Disease Improving Global
Outcomes (KDIGO) 2012 guideline emphasizes the combined role of glomerular
filtration rate (GFR) and albuminuria in determining the frequency of monitoring
of kidney function. OBJECTIVES: In this study we evaluated the prevalence of CKD
in women with a history of PE. We investigated how many seemingly healthy women
required monitoring of kidney function according to the KDIGO guideline. METHODS:
We included 775 primiparous women with a history of PE. They were at least 4
months postpartum, and had no pre-existing hypertension, diabetes or kidney
disease. We estimated GFR by the CKD-Epidemiology equation and urinary albumin
loss by albumin creatinine ratio in a 24-h urine collection. RESULTS: Most women,
669 (86.3 %), had a normal GFR and absent albuminuria. Based on the KDIGO
guideline, 13.7 % would require at least yearly monitoring of kidney function.
Only 1.4 % were classified to be at high risk for kidney function deterioration.
CONCLUSION: Monitoring of kidney function seems relevant for about one in seven
women with a history of PE, mainly due to albuminuria. Albuminuria should be
evaluated postpartum to identify those women that need further monitoring of
kidney function.
PMID- 27491316
TI - Fluoroless catheter ablation of various right and left sided supra-ventricular
tachycardias in children and adolescents.
AB - Electrophysiology study (EPS) and catheter ablation (CA) in children and
adolescents carries a potentially harmful effect of radiation exposure when
performed with the use of fluoroscopy. Our aim was to evaluate the feasibility,
safety and effectiveness of fluoroless EPS and CA of various supra-ventricular
tachycardias (SVTs) with the use of the 3D mapping system and intracardiac
echocardiography (ICE). Forty-three consecutive children and adolescents (age 13
+/- 3 years) underwent fluoroless EPS and CA for various supra-ventricular
tachycardias. A three-dimensional (3D) mapping system NavXTM was used for
guidance of diagnostic and ablation catheters in the heart. ICE was used as a
fundamental imaging tool for transseptal punctures. Acute procedural success rate
was 100 %. There were no procedure related complications and short-term follow up
(10 +/- 3 months) revealed 93 % arrhythmia free survival rate. Fluoroless CA of
various SVTs in the paediatric population is feasible, safe and can be performed
successfully with 3D mapping system and ICE.
PMID- 27491317
TI - [Femoral neck fractures in young patients].
AB - Femoral neck fractures in young patients are rare but of high clinical relevance
due to the complexity of risk factors and complications. Early stabilization and
accurate reduction are of high priority. Femoral head-preserving stabilization by
dynamic hip screws or threefold screw osteosynthesis are the methods of choice.
Postoperative results should be closely controlled in every case in order to be
able to treat possible complications in time.
PMID- 27491318
TI - Primary surgery results in no survival benefit compared to primary radiation for
oropharyngeal cancer patients stratified by high-risk human papilloma virus
status.
AB - We changed the primary oropharynx squamous cell carcinoma (OPSCC) treatment
recommendation from primary radiation therapy (RT) to tumor surgery and neck
dissection, followed by RT around the year 2000 with apparently improved
survival. However, high-risk human papilloma virus (hr-HPV)-16-caused OPSCCs have
increased during this period. Furthermore, hr-HPV+ OPSCC carry a better prognosis
than hr-HPV-negative patients. We have, therefore, evaluated the 5-year survival
in the period from 1992 to 1999 versus 2000 to 2008 stratified by hr-HPV tumor
infection status. Ninety-six OPSCC patients were treated from 1992 to 1999
compared with 136 patients from 2000 to 2008. The 5-year disease-specific
survival (DDS) and overall survival (OS) were recorded, while the health-related
quality of life (HRQoL) scores were obtained from some of the cured patients.
Thirty-eight (40 %) in the first period and 86 OPSCCs (63 %) in the second period
were hr-HPV+. In the first period, 16 versus 62 patients in the last period were
treated by neck dissection, primary tumor surgery, and RT. DSS among all the hr
HPV-negative patients in the first period was 51 versus 55 % in the second
period, and the corresponding OS was 33 versus 31 %, respectively. The DSS among
all the hr-HPV+ patients was 78 % in the first period versus 77 % in the second
period, while the OS was 71 versus 69 %, respectively. The HRQoL scores among
successfully treated patients were worse following surgery, plus RT than RT only.
The hr-HPV-adjusted 5-year survival in OPSCC patients was similar between the two
time periods. A decreased HRQoL was associated with surgical therapy, which
indicates that hr-HPV+ OPSCC patients may be treated by primary RT followed by
major surgery only if RT treatment fails.
PMID- 27491320
TI - CYP2E1 polymorphisms and nasopharyngeal carcinoma risk: a meta-analysis.
AB - The cytochrome P450 2E1 (CYP2E1) polymorphisms have been implicated in
susceptibility to nasopharyngeal carcinoma (NPC). However, the results are
inconsistent. The aim of this meta-analysis is to evaluate the association
between the CYP2E1 polymorphisms and NPC risk. All eligible case-control studies
published up to April 4, 2016 were identified by searching PubMed, Web of
Science, CNKI, Wanfang and Weipu databases. The NPC risk associated with the
CYP2E1 polymorphism was estimated for each study by odds ratios (OR) together
with its 95 % confidence interval (CI), respectively. Seven case-control studies
were included. Of those, there were seven studies (1302 cases and 1319 controls)
for RsaI/PstI polymorphism and three studies (732 cases and 642 controls) for
DraI polymorphism. Overall, a significant association was found for RsaI/PstI
polymorphism under recessive and homozygote comparison models (OR = 2.72, 95 % CI
1.73-4.25; OR = 2.64, 95 % CI 1.68-4.16, respectively), while there was no
significant association for RsaI/PstI polymorphism under other two genetic
models. When stratified by ethnicity, similar results were observed between them.
As for DraI polymorphism, we also observed a significant association under
recessive and homozygote comparison models, but not for the other two models.
This meta-analysis suggests that the CYP2E1 polymorphisms contributed to the
susceptibility of NPC, especially in Asian populations.
PMID- 27491319
TI - Will the mininvasive approach challenge the old paradigms in oral cancer surgery?
AB - In the genome era, the achievement of a safe and complete resection of oral
cancers remains a challenge for surgeons. Margin length at histopathological
examination is still considered the main indicator of oncological radicality.
However, this parameter is fraught by major limitations. Cancer aggressiveness,
and in particular its ability to spread in the surrounding tissue, most probably
influences loco-regional control and prognosis more than margin length.
Unfortunately, no molecular markers are currently available to predict tumor
aggressiveness pre-operatively. However, additional histopathological parameters,
beside margin length, could be considered to better stratify oral tumors,
including depth of invasion (DOI), perineural invasion or composite scores.
Recent advances in laser technology have established a novel surgical trend
toward a minimalist approach, named transoral laser microsurgery (TLM). TLM
provides a local control rate comparable to the one achieved by larger resections
if the margin appears disease free, independent from its length. In addition, the
clinical availability of innovative optical technologies, such as narrow band
imaging (NBI) or autofluorescence, allows more precise and tailored resections,
not simply based on clinical observation and ruler measurement. This review will
propose the possible implementation of novel procedures toward a mini-invasive
surgical approach, providing a satisfactory control rate but significantly
improving the quality of life of the patients compared to conventional surgery.
PMID- 27491321
TI - Phonoarticulation in spinocerebellar ataxia type 3.
AB - Phonoarticulation is characterized by changes in resonance, diadochokinesis,
prosody, sound frequency, vocal quality, and intraoral pressure. The main aim of
this study was to characterize the phonoarticulation in spinocerebellar ataxia
type 3 (SCA3) and correlate it with clinical and genetic factors. Thirty-one
patients with SCA3 who were subjected to spontaneous speech recordings and
phonoarticulatory diadochokinesis (DDK) participated in the study. Speech
analyses were performed starting after 10 s of spontaneous speech, by three
experienced speech therapists, using a protocol for dysarthria adapted from the
Mayo Clinic. The intra-evaluator reliability was analyzed. The lower the
patient's age at disease onset was, the more frequent the occurrences of
monofrequency and altered speech rhythm were. Articulation, DDK, resonance, and
prosody showed a moderate correlation with the number of "CAG" triplet repeats.
We conclude that the phonoarticulation of patients with Machado-Joseph disease
(MJD) is characterized by mixed dysarthrophonia with cerebellar and hypokinetic
components, and that there is a tendency toward higher frequency of
dysarthrophonia symptoms with lower age of disease onset, longer time since onset
and higher number of "CAG" triplet repeats.
PMID- 27491322
TI - Looking for the Word "Angiogenesis" in the History of Health Sciences: From
Ancient Times to the First Decades of the Twentieth Century.
AB - This review deals with the origin of the term "angiogenesis", with an attention
to John Hunter who is credited with this neologism. A part of the literature
refers to a Hunter's work dating 1787, and the other part claims the first use of
the term "angiogenesis" in the Hunter's masterpiece published in 1794. Since we
were unable to find the term "angiogenesis" in Hunter's works, this review
attempts to bring a new contribution to the historical research of this important
concept, moving from ancient times to the first decades of the twentieth century,
when "angiogenesis" begun to appear on titles of scientific articles. The
development of the knowledge on the cardiocirculatory system and the principal
steps of this fascinating subject were examined, with particular regard to
microvascular bed and vessel sprouting, and to the intriguing observations on
blood vessel neoformation that have been also made in the premicroscopic era. In
Hunter's works, the concept of angiogenesis indeed emerges, but not the term
"angiogenesis". The scientific language occurring during Hunter's time was still
old-fashioned, and the term "angiogenesis" was not one of those he used, rather a
much later neologism that sounds too modern to appear in that context. Would the
first appearance of the term "angiogenesis" occur in late nineteenth century in
studies dealing with embryogenesis and organ vascularization? The present study
aims to explore the scientific literature and to open a debate to better define
this matter.
PMID- 27491323
TI - Robotic Enucleation for Benign or Borderline Tumours of the Pancreas: A
Retrospective Analysis and Comparison from a High-Volume Centre in Asia.
AB - BACKGROUND: Enucleation is increasingly performed for benign or borderline
tumours of the pancreas because it is a parenchyma-sparing and less invasive
procedure compared to conventional pancreatectomy, which reduces the risk of
exocrine and endocrine insufficiency. This study retrospectively evaluated and
compared the pre-, intra-, and post-operative clinical characteristics after open
and robotic approaches for pancreatic enucleation. METHODS: Fifty-six cases of
enucleation for benign or borderline tumours of the pancreas treated from March
2010 to July 2015 were identified by a retrospective search. These included 25
patients who underwent an open approach and 31 patients who underwent a robotic
approach. The clinical characteristics were extracted and compared. RESULTS: The
two groups had a similar location and pathology of the tumour. The robotic group
had a significantly shorter operation time and significantly less blood loss than
the open group. The rates of clinical pancreatic fistula (PF) formation and major
complications were similar. The robotic approach could be applied for a tumour on
the right side of the pancreas without increasing the incidence of clinical PF or
other major complications. The patients with clinical PF had a significantly
shorter distance between the lesion and the main pancreatic duct (MPD).
CONCLUSION: Robotic enucleation appears to be a feasible and safe approach for
benign or borderline tumours of the pancreas and was associated with similarly
favourable surgical outcomes as the open approach. Identifying and avoiding the
MPD is an important step during enucleation.
PMID- 27491324
TI - Effect of Sitagliptin and Metformin on Prediabetes Progression to Type 2 Diabetes
- A Randomized, Double-Blind, Double-Arm, Multicenter Clinical Trial: Protocol
for the Sitagliptin and Metformin in PreDiabetes (SiMePreD) Study.
AB - BACKGROUND: The high prevalence and incidence of type 2 diabetes mellitus (DM),
and its associated morbidity and mortality, has prompted growing international
interest and effort in the primary prevention of this disease. Primary prevention
is possible since type 2 DM is preceded by prediabetes, offering a window
opportunity to treat patients, and prevent the emergence of advanced disease.
Sitagliptin is an oral dipeptidyl peptidase-IV inhibitor that preserves existing
beta cell function and increases beta cell mass. These two effects have been
demonstrated both in vitro and in animal studies, and current clinical data show
that sitagliptin is safe. Metformin, a biguanide, reduces insulin resistance and
inhibits hepatic gluconeogenesis, and has an excellent safety profile. The
combination of metformin and sitagliptin, targeting both characteristics of
prediabetes (insulin resistance and progressive beta cell degeneration), may
potentially slow or halt the progression from prediabetes to type 2 DM. This
paper describes the rationale and design of the Sitagliptin and Metformin in
PreDiabetes (SiMePreD) study. OBJECTIVE: The aim of this study is to determine
the effect of sitagliptin and metformin on progression from prediabetes to type 2
DM. The objectives of the study are to determine the effects of metformin and
placebo on glycemic endpoints, the effects of sitagliptin and metformin on
glycemic endpoints, the effects of metformin and placebo on incidence of
cardiovascular disease and death, and the effects of sitagliptin and metformin on
incidence of cardiovascular disease and death. METHODS: This is a randomized,
double-blind, multicenter clinical study that will determine if the combination
of metformin and sitagliptin is effective in preventing the progression from
prediabetes to type 2 DM. The study will contain two arms (metformin/sitagliptin
and metformin/placebo). Primary endpoints include the number of subjects
progressing from prediabetes to type 2 DM, the number of cardiovascular events,
and the number of deaths. The planned duration of the study is five years, and
410 subjects will be included in each group. Data analyses will include
clinically relevant measures (eg, numbers needed to treat and numbers needed to
harm) and will be performed according to the intention-to-treat principle.
RESULTS: This study is currently in the process of acquiring research funding.
CONCLUSIONS: The SiMePreD study is the first study to investigate the utility of
sitagliptin in combination with metformin for the primary prevention of type 2
DM. .
PMID- 27491325
TI - How to justify a ban on doping?
AB - BACKGROUND: This article deals with arguments that challenge the possibility of
an ethical justification for a doping ban. HYPOTHESIS/PURPOSE: It shows that a
justification for the doping ban is only possible if its implementation can be
safeguarded. STUDY DESIGN: Systematic review. METHODS: Based on the proposition
of the game theory, this article examines the scope of the arguments of
naturalness, health, equal opportunity and fairness used in scientific
literature. RESULTS/CONCLUSIONS: Ceteris paribus, athletes will always prefer a
situation that presents no health risk to a situation in which they face a threat
to their health. They will therefore consent to a doping ban on the condition
that it is ensured that all parties are bound to this rule, so that anyone
complying with the rules will not be afraid of losing the competition as a
result. For even if we condoned self-harm, it could still be argued plausibly
that the individual should not suffer more disadvantages than absolutely
necessary for the sake of gaining an advantage over others. Of course, it is
possible to plead for a restricted approval of doping measures with acceptable
risk. But even taking minor risks would not seem sensible under the condition
that all participants without exception adhere to the same conditions when there
is the option to renounce the (avoidable) risks. So as far as the use of
performance-enhancing substances or methods is concerned, we can maintain that
even if minor health risks are to be expected, a ban on doping can be justified
from an ethical point of view.
PMID- 27491327
TI - First digit macrodactyly and carpal tunnel syndrome caused by giant median nerve
with macrodystrophia lipomatosa.
PMID- 27491326
TI - Complex regional pain syndrome.
AB - INTRODUCTION: Complex regional pain syndrome (CRPS) is a chronic pain condition
that can occur after a minor trauma or surgery. It is a multifactorial condition
with a complex cause and even more complex pathophysiology. There are
disturbances and changes in the sympathetic, somatosensory and motor nervous
system, resulting in severe pain and disability. Patients with CRPS can have
their quality of life and functional ability greatly affected and they need
appropriate and interdisciplinary interventions. PURPOSE: This article
contributes towards an up-to-date knowledge and an overall view of CRPS, which
can contribute to a structured and systematic rehabilitation process for
patients. IMPLICATIONS: This Masterclass describes a functional restoration
algorithm to assist therapists in the development of a treatment plan based on
the available evidence and international guidelines. Early diagnosis and
treatment is of great importance as patients (adults and children), can be
severely affected in their functional capacity and quality of life.
PMID- 27491328
TI - Life Sciences Discovery and Technology Highlights.
PMID- 27491330
TI - Macromol. Biosci. 8/2016.
AB - Back Cover: The authors have created polymers which release insulin using light.
These materials utilize insulin itself as the primary monomer and therefore
achieve a very high density (85% w/w insulin). This near perfect density makes
them ideal as photoactivated depots of insulin. Further details can be found in
the article by Bhagyesh R. Sarode, Piyush K. Jain, Simon H. Friedman on page
1138.
PMID- 27491333
TI - Adaptive finite difference for seismic wavefield modelling in acoustic media.
AB - Efficient numerical seismic wavefield modelling is a key component of modern
seismic imaging techniques, such as reverse-time migration and full-waveform
inversion. Finite difference methods are perhaps the most widely used numerical
approach for forward modelling, and here we introduce a novel scheme for
implementing finite difference by introducing a time-to-space wavelet mapping.
Finite difference coefficients are then computed by minimising the difference
between the spatial derivatives of the mapped wavelet and the finite difference
operator over all propagation angles. Since the coefficients vary adaptively with
different velocities and source wavelet bandwidths, the method is capable to
maximise the accuracy of the finite difference operator. Numerical examples
demonstrate that this method is superior to standard finite difference methods,
while comparable to Zhang's optimised finite difference scheme.
PMID- 27491332
TI - Use of the physical environment to support everyday activities for people with
dementia: A systematic review.
AB - Difficulty with everyday activities is a key symptom and defining feature of
dementia, relating to subjective reports of well-being and overall quality of
life. One way to support individuals in their daily activities is by modifying
the physical environment to make it easier to interact with during activity
performance. This systematic review explores the range of studies available using
physical environmental strategies to support performance in everyday activities
for people with dementia. Seventy-two relevant studies were identified by the
search. Physical environmental strategies included changes to the global
environment and to architectural features, use of moveable environmental aids and
tailored individual approaches. Strategies supported general everyday activity
functioning (N = 19), as well as specific activities, particularly mealtimes (N =
15) and orientation in space (N = 16); however, few studies were found that
focused on aspects of personal care such as dressing (N = 1) and showering or the
preferred hobbies of individuals (N = 0). Overall, there appeared to be a lack of
research within private home environments, and of studies which specify the
dementia syndrome or the whole neuropsychological profile of people with
dementia. More work is needed to extend theoretical understandings of how people
with dementia interact with their environments so that these spaces can be
designed to further support activities of daily living performance. Future work
in this field could also incorporate the perspectives and preferences of those
living with dementia.
PMID- 27491334
TI - Developing a Data Visualization System for the Bank of America Chicago Marathon
(Chicago, Illinois USA).
AB - As one of the largest marathons worldwide, the Bank of America Chicago Marathon
(BACCM; Chicago, Illinois USA) accumulates high volumes of data. Race organizers
and engaged agencies need the ability to access specific data in real-time. This
report details a data visualization system designed for the Chicago Marathon and
establishes key principles for event management data visualization. The data
visualization system allows for efficient data communication among the organizing
agencies of Chicago endurance events. Agencies can observe the progress of the
race throughout the day and obtain needed information, such as the number and
location of runners on the course and current weather conditions. Implementation
of the system can reduce time-consuming, face-to-face interactions between
involved agencies by having key data streams in one location, streamlining
communications with the purpose of improving race logistics, as well as medical
preparedness and response. Hanken T , Young S , Smilowitz K , Chiampas G ,
Waskowski D . Developing a data visualization system for the Bank of America
Chicago Marathon (Chicago, Illinois USA). Prehosp Disaster Med. 2016;31(5):572
577.
PMID- 27491337
TI - Thermalized connectivity networks of jammed packings.
AB - Jammed packings of repulsive elastic spheres have emerged as a rich model system
within which the elastic properties of disordered glassy materials may be
elucidated. Most of the work on these packings has focused on the case of
vanishing temperature. Here, we explore the elastic properties of the associated
connectivity network for finite temperatures, ignoring the breaking of bonds and
the formation of new ones. Using extensive Monte Carlo simulations, we find that,
as the temperature is increased, the resulting spring network shrinks and
exhibits a rapidly softening bulk modulus via a cusp. Moreover, the shear modulus
stiffens in a fixed volume ensemble but not in a fixed pressure ensemble. These
counter-intuitive behaviors may be understood from the characteristic spectrum of
soft modes near isostaticity, which resembles the spectrum of a rod near its
buckling instability. Our results suggest a generic mechanism for negative
thermal expansion coefficients in marginal solids. We discuss some consequences
of bond breaking and an apparent analogy between thermalization and shear.
PMID- 27491335
TI - Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque
stability in ApoE(-/-) mice.
AB - Atherosclerosis is a chronic inflammatory disease characterized by formation of
lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like
and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that
regulates versican turnover in the arterial wall and atherosclerotic plaques.
Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques
and in the plasma of acute coronary syndrome patients. Nevertheless, whether
increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal
role in atherogenesis remains unknown. In this work, we investigated the role of
ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE(-/
)) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in
plaques as atherosclerosis progresses in ApoE(-/-) mice. ApoE(-/-)Adamts4(-/-)
double knockout mice presented a significant reduction in plaque burden at 18
weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a
significantly reduced plaque vulnerability index characterized by reduced lipid
content and macrophages accompanied with a significant increase in smooth muscle
cells, collagen deposition and fibrotic cap thickness. The reduced
atherosclerosis is accompanied by an altered plasma inflammatory cytokine
profile. These results demonstrate for the first time that ADAMTS4 contributes to
diet induced atherosclerosis in ApoE(-/-) mice.
PMID- 27491336
TI - Effect of alpha-linolenic acid-modified low molecular weight chondroitin sulfate
on atherosclerosis in apoE-deficient mice.
AB - METHODS: 8-week-age male ApoE(-/-) mice were fed with the atherogenic diet
together with or without tested compounds (rosuvastatin calcium, alpha-LNA-LMWCS,
LMWCS and alpha-LNA) for 16 weeks. When the animals were killed, blood plasma was
isolated to test the level of TC, LDL-C, TNF-alpha, IL-6 and CRP by biochemistry
analysis and ELISA method. The whole aorta and aortic root sections were also
collected to study atherogenesis level and reveal the possible mechanism by
histological examination, real-time PCR and Western blot analysis. RESULTS: The
level of TC, LDL-C, TNF-alpha, IL-6 and CRP in plasma in H-LNA-LMWCS group were
significantly lower than those of the control group (rosuvastatin calcium).
Plaques in H-LNA-LMWCS group showed higher content of smooth muscle cells, lower
content of lipid and macrophages, and lower mRNA levels of TNF-alpha, IL-6, CRP,
MCP-1, VCAM-1 and ICAM-1 than those in the control group. In addition, alpha-LNA
LMWCS could reduce the nuclear translocation of NF-kappaB, inhibit expressions of
p-ERK1/2, p-p38, MCP-1, VCAM-1 and ICAM-1 in mice aorta. CONCLUSION: alpha-LNA
LMWCS exhibited anti-atherosclerosis effect through regulating the lipid
metabolism and diminishing the synthesis of pro-inflammatory cytokines. The
possible mechanism may be that alpha-LNA-LMWCS could influence MAPK/ NF-kappaB
related signal pathway. GENERAL SIGNIFICANCE: The results may provide significant
suggestions for the application of alpha-LNA-LMWCS in anti-atherosclerosis.
PMID- 27491338
TI - Zero-temperature quantum annealing bottlenecks in the spin-glass phase.
AB - A promising approach to solving hard binary optimization problems is quantum
adiabatic annealing in a transverse magnetic field. An instantaneous ground state
initially a symmetric superposition of all possible assignments of N qubits-is
closely tracked as it becomes more and more localized near the global minimum of
the classical energy. Regions where the energy gap to excited states is small
(for instance at the phase transition) are the algorithm's bottlenecks. Here I
show how for large problems the complexity becomes dominated by O(log N)
bottlenecks inside the spin-glass phase, where the gap scales as a stretched
exponential. For smaller N, only the gap at the critical point is relevant, where
it scales polynomially, as long as the phase transition is second order. This
phenomenon is demonstrated rigorously for the two-pattern Gaussian Hopfield
model. Qualitative comparison with the Sherrington-Kirkpatrick model leads to
similar conclusions.
PMID- 27491339
TI - Evolutionary Developmental Biology (Evo-Devo) Research in Latin America.
AB - Famous for its blind cavefish and Darwin's finches, Latin America is home to some
of the richest biodiversity hotspots of our planet. The Latin American fauna and
flora inspired and captivated naturalists from the nineteenth and twentieth
centuries, including such notable pioneers such as Fritz Muller, Florentino
Ameghino, and Leon Croizat who made a significant contribution to the study of
embryology and evolutionary thinking. But, what are the historical and present
contributions of the Latin American scientific community to Evo-Devo? Here, we
provide the first comprehensive overview of the Evo-Devo laboratories based in
Latin America and describe current lines of research based on endemic species,
focusing on body plans and patterning, systematics, physiology, computational
modeling approaches, ecology, and domestication. Literature searches reveal that
Evo-Devo in Latin America is still in its early days; while showing encouraging
indicators of productivity, it has not stabilized yet, because it relies on few
and sparsely distributed laboratories. Coping with the rapid changes in national
scientific policies and contributing to solve social and health issues specific
to each region are among the main challenges faced by Latin American researchers.
The 2015 inaugural meeting of the Pan-American Society for Evolutionary
Developmental Biology played a pivotal role in bringing together Latin American
researchers eager to initiate and consolidate regional and worldwide
collaborative networks. Such networks will undoubtedly advance research on the
extremely high genetic and phenotypic biodiversity of Latin America, bound to be
an almost infinite source of amazement and fascinating findings for the Evo-Devo
community.
PMID- 27491340
TI - The Association Between Sexual Health and Physical, Mental, and Social Health in
Adolescent Women.
AB - PURPOSE: Developmental models link sexual well-being to physical,
mental/emotional, and social well-being, yet little empirical literature
evaluates these relationships in adolescents. Better understanding of how and
when sexuality complements other aspects of health may yield important points to
enhance existing health education and prevention efforts. METHODS: Data were
drawn from a 10-year longitudinal cohort study of sexual relationships and sexual
behavior among adolescent women (N = 387; 14-17 years at enrollment). Sexual
health data were drawn from quarterly partner-specific interviews and were linked
to physical, mental/emotional, and social health information in annual
questionnaires. Random intercept, mixed effects linear, ordinal logistic, or
binary logistic regression were used to estimate the influence of sexual health
on health and well-being outcomes (Stata, v.23, StataCorp, College Station, TX).
All models controlled for participant age and race/ethnicity. RESULTS: Higher
sexual health was significantly associated with less frequent nicotine and
substance use, lower self-reported depression, lower thrill seeking, higher self
esteem, having fewer friends who use substances, higher religiosity, better
social integration, lower frequency of delinquent behavior and crime, and more
frequent community group membership. Sexual health was not associated with the
number of friends who used cigarettes. CONCLUSIONS: Positive sexually related
experiences in romantic relationships during adolescence may complement physical,
mental/emotional, and social health. Addressing specific aspects of healthy
sexual development during clinical encounters could dually help primary
prevention and health education address other common adolescent health issues.
PMID- 27491341
TI - Rapid detection of European orthobunyaviruses by reverse transcription loop
mediated isothermal amplification assays.
AB - The development of reverse transcriptase loop-mediated isothermal amplification
(RT-LAMP) assays are described herein for the detection of two orthobunyaviruses
(Bunyaviridae), which represent the two main serogroups found in mosquitoes in
Central Europe. The RT-LAMP assays were optimized for the detection of Tahyna
virus (a California encephalitis group virus found in Aedes sp or Ochlerotatus sp
mosquitoes) and Batai virus (also called Calovo virus, a Bunyamwera group virus
found in Anopheles maculipennis s.l. mosquitoes) nucleic acid using endemic
European virus isolates. The sensitivity of the RT-LAMP assays was determined to
be comparable to that of conventional tests, with a limit of detection<0.1 pfu
per reaction. The assays can be performed in 60min under isothermal conditions
using very simple equipment. Furthermore, it was possible to proceed with the
assays without nucleic acid extraction, albeit at a 100-fold loss of sensitivity.
The RT-LAMP assays are a sensitive, cost-efficient method for both arbovirus
surveillance as well as diagnostic laboratories to detect the presence of these
endemic orthobunyaviruses.
PMID- 27491342
TI - Prevalence of Plasmodium falciparum transmission reducing immunity among primary
school children in a malaria moderate transmission region in Zimbabwe.
AB - Malaria continues to cause alarming morbidity and mortality in more than 100
countries worldwide. Antigens in the various life cycle stages of malaria
parasites are presented to the immune system during natural infection and it is
widely recognized that after repeated malaria exposure, adults develop partially
protective immunity. Specific antigens of natural immunity represent among the
most important targets for the development of malaria vaccines. Immunity against
the transmission stages of the malaria parasite represents an important approach
to reduce malaria transmission and is believed to become an important tool for
gradual elimination of malaria. Development of immunity against Plasmodium
falciparum sexual stages was evaluated in primary school children aged 6-16 years
in Makoni district of Zimbabwe, an area of low to modest malaria transmission.
Malaria infection was screened by microscopy, rapid diagnostic tests and finally
using nested PCR. Plasma samples were tested for antibodies against recombinant
Pfs48/45 and Pfs47 by ELISA. Corresponding serum samples were used to test for P.
falciparum transmission reducing activity in Anopheles stephensi and An. gambiae
mosquitoes using the membrane feeding assay. The prevalence of malaria diagnosed
by rapid diagnostic test kit (Paracheck)TM was 1.7%. However, of the randomly
tested blood samples, 66% were positive by nested PCR. ELISA revealed prevalence
(64% positivity at 1:500 dilution, in randomly selected 66 plasma samples) of
antibodies against recombinant Pfs48/45 (mean A 405nm=0.53, CI=0.46-0.60) and
Pfs47 (mean A405nm=0.91, CI=0.80-1.02); antigens specific to the sexual stages.
The mosquito membrane feeding assay demonstrated measurable transmission reducing
ability of the samples that were positive for Pfs48/45 antibodies by ELISA.
Interestingly, 3 plasma samples revealed enhancement of infectivity of P.
falciparum in An. stephensi mosquitoes. These studies revealed the presence of
antibodies with transmission reducing immunity in school age children from a
moderate transmission area of malaria, and provide further support to exploit
target antigens such as Pfs48/45 for further development of a malaria
transmission blocking vaccine.
PMID- 27491344
TI - Acute effects of walking and combined exercise on oxidative stress and vascular
function in peripheral artery disease.
AB - The aim of this study was to compare the effects of a single session of walking
and combined exercise on oxidative stress and vascular function in peripheral
arterial disease patients. Thirteen patients with peripheral arterial disease
underwent two experimental sessions in random order: walking (ten sets of 2-min
walking at the speed corresponding to the onset of claudication pain with 2-min
interval between sets) and combined exercise (1 * 10 reps in eight resistance
exercises plus five-two-minute sets of walking). Before and after the exercise,
vascular function (blood flow, leg vascular resistance and blood-flow
postreactive hyperaemia) and oxidative stress (malondialdehyde and plasma nitrite
levels) were obtained. Blood flow increased similarly after both sessions, whilst
leg vascular resistance decreased similarly after both sessions. Plasma nitrite
increased only after the combined exercise. Malondialdehyde decreased after both
sessions, and the decrease was greater after combined exercise. As a conclusion,
a single session of combined exercise improves blood flow and leg vascular
resistance similarly to walking session; however, combined exercise promoted
better effects on oxidative stress.
PMID- 27491343
TI - Culicoides species composition and environmental factors influencing African
horse sickness distribution at three sites in Namibia.
AB - African horse sickness (AHS) is one of the most lethal infectious, non
contagious, vector-borne disease of equids. The causative agent, African horse
sickness virus (AHSV) is transmitted via Culicoides midges (Diptera:
Ceratopogonidae). AHS is endemic to Namibia but detailed studies of Culicoides
communities and influencing environmental parameters are limited. This study aims
to determine the Culicoides species composition at three different sites and to
assess environmental parameters influencing the geographical distribution of AHS
in Namibia. Weekly collections of Culicoides were made during the AHS peak season
from January to May for 2013 and 2014 using the Onderstepoort 220V UV-light trap.
Out of 397 collections made, 124 collections (3287 Culicoides) were analysed for
AHSV presence with RT-qPCR. A total of 295 collections were analysed for total
Culicoides (all collected Culicoides individuals) and in 75% of these collections
the Culicoides were identified to species level. C. imicola was the dominant
species with proportional representation of 29.9%. C. subschultzei, C.
exspectator and C. ravus each contribute more than 10% to the species
composition. The lowest number of Culicoides was collected at Aus 9980, a total
of 21819 at Windhoek and the highest number at Okahandja 47343. AHSV was present
at all three sites during 2013 but only in Windhoek and Okahandja during 2014.
Multivariate analyses of data from the two year survey indicate the environmental
parameters in order of importance for the distribution of AHS in Namibia as
precipitation>temperature>clay>relative humidity>NDVI. The implication of these
findings is that any precipitation event increases Culicoides numbers
significantly. Together with these results the high number of species found of
which little is known regarding their vector competence, add to the complexity of
the distribution of AHS in Namibia.
PMID- 27491345
TI - In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy.
AB - Ischemia-induced hypoxia elicits retinal neovascularization and is a major
component of several blinding retinopathies such as retinopathy of prematurity
(ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently,
noninvasive imaging techniques capable of detecting and monitoring retinal
hypoxia in living systems do not exist. Such techniques would greatly clarify the
role of hypoxia in experimental and human retinal neovascular pathogenesis. In
this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe
capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo
and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced
retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4
dependent fluorescence activity in this animal model. In retinal cells and mouse
retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia
selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as
indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as
indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX
4 could potentially serve as the basis for in vivo fluorescence-based hypoxia
imaging techniques, providing a tool for investigators to understand the
pathogenesis of ischemic retinopathies and for physicians to address unmet
clinical needs.
PMID- 27491347
TI - Oil-in-Water Emulsions Stabilized by Carboxymethylated Lignins: Properties and
Energy Prospects.
AB - We take advantage of the amphiphilic properties of technical lignin
macromolecules and their inherent high calorific values to formulate oil-in-water
(O/W) fuel emulsions with high internal-phase ratios. For the oil phase, we used
a combustible hydrocarbon (kerosene) with a measured equivalent alkane carbon
number of 12. To adjust the balance of affinity with the oil and water phases and
their surface activity, pine kraft lignins were carboxymethylated to different
degrees, as quantified by (13) C NMR spectroscopy, potentiometric titrations, and
zeta potential measurements. Carboxymethylated lignins (CMLs) with a degree of
substitution of 30 % displayed a critical aggregation concentration of 3 %. The
salinity and pH of the aqueous phase were chosen as formulation variables and
adjusted within the Winsor framework. The O/W emulsions were produced by
following standard protocols. The drop-size distributions of emulsions with
varying pH, degree of substitution, and composition (water-to-oil ratio, WOR)
were determined, and the long-term stabilities and rheological behavior of these
emulsions were analyzed. Most of the obtained O/W fuel emulsions showed shear
thinning behavior with a drop size of approximately 2.5 MUm and were stable for
over 30 days. The combustion of the lignins and their respective emulsions was
performed, and their higher heating values (HHVs) were quantified. The HHVs of
CML and a high-internal-phase (WOR=30:70) O/W emulsion were 20 and 30 MJ kg(-1) ,
respectively. Overall, we propose the stabilization of O/W fuel emulsions by
lignin as an important avenue in the utilization of this abundant
biomacromolecule.
PMID- 27491346
TI - Patient Perspectives Regarding Ethics of Spinal Column Stimulators in the
Surgical Management of Persistent Postoperative Neuropathic Pain.
AB - OBJECTIVE: The aim of this study is to better understand perspectives of patients
with persistent postoperative neuropathic pain (PPNP) and assess perceptions of
the ethical issues surrounding their structural spinal surgeon also performing
spinal cord stimulation (SCS). METHODS: Semistructured face-to-face interviews
with 20 neurosurgical spine patients were conducted. Patients were recruited from
the neurosurgery clinics at Toronto Western Hospital and were seen in
consultation for PPNP. Interviews were transcribed and subjected to thematic
analysis using open and axial coding. RESULTS: The range of the duration of
participants' preoperative symptoms varied from one month to more than 20 years,
and was primarily back dominant (13/20). The median time since patients most
recently underwent spinal surgery was three years. The majority of patients
(15/20) do not view their current condition of PPNP as a failure of their initial
spine surgeon. The most commonly reported reason for this is that patients
trusted their physician and clear communication between the physician and the
patient, prior to their surgery, ensured an understanding of the goals of the
procedure. Nearly unanimously (19/20), patients did not perceive an ethical
problem with a surgeon performing a structurally corrective spinal surgery and
subsequently also implanting a SCS device if the same patient that develops
medically refractory PPNP. CONCLUSIONS: This is the first clinical qualitative
study of values and ethical perceptions of patients with medically refractory
PPNP. Our findings provide a framework for understanding the values of patients
with PPNP and demonstrate that a strong surgeon-patient relationship can
ameliorate concerns surrounding PPNP and SCS implantation.
PMID- 27491348
TI - Richter's Hernia After Laparoscopic Surgery.
PMID- 27491350
TI - Ever HRD a ubiquitin-gated channel?
AB - Elimination of misfolded proteins of the endoplasmic reticulum (ER) requires
their retrotranslocation from the ER to the cytosol via membrane-bound ubiquitin
ligase complexes. Baldridge and Rapoport now reconstitute a key step of
retrotranslocation, demonstrating a protein conduit gated by ubiquitination.
PMID- 27491349
TI - Synthesis of (18) F-Difluoromethylarenes from Aryl (Pseudo) Halides.
AB - A general method for the synthesis of [(18) F]difluoromethylarenes from [(18)
F]fluoride for radiopharmaceutical discovery is reported. The method is
practical, operationally simple, tolerates a wide scope of functional groups, and
enables the labeling of a variety of arenes and heteroarenes with radiochemical
yields (RCYs, not decay-corrected) from 10 to 60 %. The (18) F-fluorination
precursors are readily prepared from aryl chlorides, bromides, iodides, and
triflates. Seven (18) F-difluoromethylarene drug analogues and
radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [(18) F]DAA1106
were synthesized to show the potential of the method for applications in PET
radiopharmaceutical design.
PMID- 27491351
TI - Reliability of immunocytochemistry and fluorescence in situ hybridization on fine
needle aspiration cytology samples of breast cancers: methodological issues.
PMID- 27491352
TI - Substituent effects of N4 Schiff base ligands on the formation of fluoride
bridged dicobalt(ii) complexes via B-F abstraction: structures and magnetism.
AB - We report the synthesis of two fluoride bridged cobalt(ii) dimers - [Co(MU
F)(pnN4-PhCl)2(OH2)(MeCN)](BF4)3 (1) and [Co(MU-F)2(pnN4-PhCl)2](BF4)2 (2) - and
related complexes derived from propyl-bridged N4 Schiff base plus pyridine
ligands. Notably, the bridging fluoride ion(s) emanate from B-F abstraction
processes on the BF4 anions in the starting salt, [Co(H2O)6](BF4)2. Two types of
bridging motifs are generated - mono-bridged (MU-F) or di-bridged (MU-F)2-
synthetically differentiated by the absence or presence of pyridine,
respectively, during metalation. The synergistic roles of pyridine and the
(ClPh)N4 ligand in promoting B-F abstraction were clarified by the isolation and
crystallization of the simple tetrakis-pyridine monomeric complex
[Co(py)4(MeCN)2](BF4)2 (4) [no B-F abstraction]; subsequent addition of the
(ClPh)N4 ligand to 4 resulted in formation of the dimeric, di-bridged complex 2.
Omission of pyridine during metalation resulted in formation of the mono-bridged
dimer 1. The bulky chlorophenyl substituents were obligate for B-F abstraction,
as metalation of the unsubstituted N4 ligand resulted in the non-fluoride-bridged
dimer, [Co(pnN4)3](BF4)4 (3). In magnetic studies, complexes 1 (MUeff = 6.24MUB,
298 K) and 2 (MUeff = 7.70MUB, 298 K) both exhibit antiferromagnetic (AFM)
coupling, but to different extents. Temperature-dependent magnetic susceptibility
measurements (SQUID, 2 -> 300 K) reveal that the linearity of the mono-fluoride
bridge in 1 [?Co-F-Co = 159.47(11) degrees ] results in very strong AFM coupling
(J = -14.9 cm(-1)). In contrast, the more acute Co2F2 diamond core [?Co-F-Co =
98.8(2) degrees , 99.1(2) degrees ] results in a smaller extent of AFM coupling
(J = -2.97 cm(-1)). Overall, the results indicate the 'non-innocence' of the BF4
counterion in cobalt(ii) chemistry, and dimers 1 and 2 affirm the effect of the
geometry of the bridging fluoride ion(s) in determining the extent of AFM
coupling.
PMID- 27491353
TI - Laminin-111 Inhibits Bovine Fertilization but Improves Embryonic Development in
vitro, and Receptor Integrin-beta1 is Involved in Sperm-Oocyte Binding.
AB - This study detected the distribution of laminin during embryonic formation by
immunofluorescence. To determine the possible function of laminin on
developmental ability of in vitro fertilized embryos, the presumptive zygotes
were divided and transferred to CR1aa medium supplemented with different
concentrations (0 MUg/ml, 5 MUg/ml, 10 MUg/ml and 20 MUg/ml) of laminin. To
explore the association with sperm-oocyte fusion, oocytes and/or sperm were pre
incubated with laminin or anti-beta1 antibody before insemination. Laminin was
absent in mature oocytes and could be detected first at the 8-cell stage and then
displayed an increasing tendency. Adding 10 MUg/ml laminin to the culture medium
improved embryonic development including cleavage rate, blastocyst rate, total
cell numbers in the blastocyst and cell numbers in the inner cell mass. Laminin
inhibited sperm-oocyte fusion when incubated with oocytes and/or sperm before in
vitro fertilization, and only integrin-beta1 of sperm was involved in sperm
oocyte binding. Inhibition may be caused by blocking beta1, but why laminin
inhibits fertilization is still unknown. The results suggest that laminin plays
an important role during embryonic formation and has a negative function in sperm
oocyte fusion, but improves embryonic development. However, only integrin-beta1
is involved in sperm-oocyte binding.
PMID- 27491354
TI - User survey finds rapid evidence reviews increased uptake of evidence by Veterans
Health Administration leadership to inform fast-paced health-system decision
making.
AB - BACKGROUND: To provide evidence synthesis for faster-paced healthcare decision
making, rapid reviews have emerged as a streamlined alternative to standard
systematic reviews. In 2012, the Veterans Affairs Evidence-based Synthesis
Program (VA ESP) added rapid reviews to support Veterans Health Administration
(VHA) operational partners' more urgent decision-making needs. VHA operational
partners play a substantial role in dissemination of ESP rapid reviews through a
variety of routes, including posting on the VA ESP's public website (
http://www.hsrd. RESEARCH: va.gov/publications/esp/ ). As demand for rapid
reviews rises, much progress has been made in characterizing methods and
practices. However, evidence synthesis organizations still seek to better
understand how and when rapid reviews are being used. METHODS: The VA ESP
administered an online survey to rapid review operational partners. The survey
assessed the nature of decision-making needs, overall perception of review
content, resulting actions, and implementation timeframe. We use descriptive
statistics and narrative methods to summarize findings. RESULTS: Between October
2011 and April 2015, we completed 12 rapid reviews for 35 operational partners.
Operational partners were primarily non-academic subject matter experts with VA
operations' decision-making authority. The most common topic categories reviewed
were policy or system (50 %) or process of care (42 %) initiatives. Median report
completion time was 14.5 weeks. Survey response rate was 46 %, with at least one
operational partner responding for 92 % of reports. Reviews served multiple
purposes including policy directive or regulation (72 %), supporting program
development and evaluation (55 %), identifying future research needs (45 %), and
determining implementation strategy (45 %). Overall, operational partners'
perception of report content was positive. A majority of rapid reviews were used
immediately and informed actions ranking high on the Institute of Medicine's
Degrees of Impact framework: 45.4 % effected change, 18.2 % inspired action, 18.2
% informed the field, 9.1 % received recognition, and 9.1 % spread a message.
CONCLUSIONS: VA ESP rapid reviews have increased the VHA's uptake of evidence to
inform time-sensitive system-level decision-making. Key areas of interest for
future evaluation include assessing user perception of our streamlined methods
and the quality of our efforts to inform users of these methods, as well as
comparing the usability and impact of our rapid and standard systematic reviews.
PMID- 27491355
TI - A case of epidemic myalgia with symptoms resembling acute purulent spondylitis
and discitis.
AB - BACKGROUND: Epidemic myalgia is a disease that presents with fever and extreme
myalgia of the trunk due to an acute enterovirus infection. The trunk pain is
mainly in the chest or in the epigastrium. We aimed to highlight a case of
epidemic myalgia where initial diagnosis needed differentiation from acute
purulent spondylitis and discitis. CASE PRESENTATION: A 33-year-old woman
presented with fever, chills, and acute episodes of low back pain. The sole
unusual finding was pain upon spinal percussion, limited to the 4th and 5th
lumbar vertebrae. Spinal MRI showed no abnormality. Paired serum samples from
disease days 4 and 15 showed a significant increase in coxsackievirus B3
neutralizing antibodies. Based on this course, we diagnosed epidemic myalgia.
CONCLUSIONS: Epidemic myalgia should be considered when differentiating acute low
back pain accompanied by fever.
PMID- 27491356
TI - Clinical application of whole-genome low-coverage next-generation sequencing to
detect and characterize balanced chromosomal translocations.
AB - Individuals carrying balanced translocations have a high risk of birth defects,
recurrent spontaneous abortions and infertility. Thus, the detection and
characterization of balanced translocations is important to reveal the genetic
background of the carriers and to provide proper genetic counseling. Next
generation sequencing (NGS), which has great advantages over other methods such
as karyotyping and fluorescence in situ hybridization (FISH), has been used to
detect disease-associated breakpoints. Herein, to evaluate the application of
this technology to detect balanced translocations in the clinic, we performed a
parental study for prenatal cases with unbalanced translocations. Eight candidate
families with potential balanced translocations were investigated using two
strategies in parallel, low-coverage whole-genome sequencing (WGS) followed-up by
Sanger sequencing and G-banding karyotype coupled with FISH. G-banding analysis
revealed three balanced translocations, and FISH detected two cryptic
submicroscopic balanced translocations. Consistently, WGS detected five balanced
translocations and mapped all the breakpoints by Sanger sequencing. Analysis of
the breakpoints revealed that six genes were disrupted in the four apparently
healthy carriers. In summary, our result suggested low-coverage WGS can detect
balanced translocations reliably and can map breakpoints precisely compared with
conventional procedures. WGS may replace cytogenetic methods in the diagnosis of
balanced translocation carriers in the clinic.
PMID- 27491357
TI - Controlled drug release to cancer cells from modular one-photon visible light
responsive micellar system.
AB - We present a one-photon visible light-responsive micellar system for efficient,
on-demand delivery of small molecules. Release is mediated by a novel class of
photochromic material - donor-acceptor Stenhouse adducts (DASAs). We demonstrate
controlled delivery of small molecules such as the chemotherapeutic agent
(paclitaxel) to human breast cancer cells triggered by micellar switching with
low intensity, visible light.
PMID- 27491358
TI - Open questions: what about the 'other' Rho GTPases?
AB - Rho GTPases have many and diverse roles in cell physiology, and some family
members are very well studied, including RhoA, Rac1 and Cdc42. But many are
relatively neglected, and fundamental questions about their mechanisms and
functions remain open.
PMID- 27491359
TI - Repeatability of swept-source optical coherence tomography retinal and choroidal
thickness measurements in neovascular age-related macular degeneration.
AB - BACKGROUND: The aim was to determine the intrasession repeatability of swept
source optical coherence tomography (SS-OCT)-derived retinal and choroidal
thickness measurements in eyes with neovascular age-related macular degeneration
(nAMD). METHODS: A prospective study consisting of patients with active nAMD
enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London.
Patients underwent three 12*9 mm macular raster scans using the deep range
imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal
and choroidal thicknesses were calculated for the ETDRS macular subfields.
Repeatability was calculated according to methods described by Bland and Altman.
RESULTS: 39 eyes of 39 patients with nAMD were included with a mean (+/-SD) age
of 73.9 (+/-7.2) years. The mean (+/-SD) retinal thickness of the central macular
subfield was 225.7 MUm (+/-12.4 MUm). The repeatability this subfield, expressed
as a percentage of the mean central macular subfield thickness, was 23.2%. The
percentage repeatability of the other macular subfields ranged from 13.2% to
28.7%. The intrasession coefficient of repeatability of choroidal thickness of
the central macular subfield was 57.2 MUm with a mean choroidal thickness (+/-SD)
of 181 MUm (+/-15.8 MUm). CONCLUSIONS: This study suggests that a change >23.2%
of retinal thickness and 57.2 MUm choroidal thickness in the central macular
subfield is required to distinguish true clinical change from measurement
variability when using the DRI OCT-1 device to manage patients with nAMD.
PMID- 27491360
TI - Stargardt disease: clinical features, molecular genetics, animal models and
therapeutic options.
AB - Stargardt disease (STGD1; MIM 248200) is the most prevalent inherited macular
dystrophy and is associated with disease-causing sequence variants in the gene
ABCA4 Significant advances have been made over the last 10 years in our
understanding of both the clinical and molecular features of STGD1, and also the
underlying pathophysiology, which has culminated in ongoing and planned human
clinical trials of novel therapies. The aims of this review are to describe the
detailed phenotypic and genotypic characteristics of the disease, conventional
and novel imaging findings, current knowledge of animal models and pathogenesis,
and the multiple avenues of intervention being explored.
PMID- 27491362
TI - Synthesis of Breathing Metallopolymer Hollow Spheres for Redox-Controlled
Release.
AB - A convenient synthetic approach for the preparation of uniform metallopolymer
containing hollow spheres based on 2-(methacryloyloxy)ethyl ferrocenecarboxylate
(FcMA) as monomer by sequential starved feed emulsion polymerization is
described. Core/shell particles consisting of a noncrosslinked poly(methyl
methacrylate) core and a slightly crosslinked ferrocene-containing shell allows
for the simple dissolution of core material and, thus, monodisperse
metallopolymer hollow spheres are obtained. Since PFcMA is incorporated in the
particle shell, herein investigated hollow spheres can be addressed by external
triggers, i.e., solvent variation and redox chemistry in order to change the
particle swelling capability. PFcMA-containing core/shell particles and hollow
spheres are characterized by transmission electron microscope (TEM), scanning
electron microscopy, cryogenic TEM, thermogravimetric analysis, and dynamic light
scattering in terms of size, size distribution, hollow sphere character, redox
responsiveness, and composition. Moreover, the general suitability of prepared
stimulus-responsive nanocapsules for the use in catch-release systems is
demonstrated by loading the nanocapsules with malachite green as model payload
followed by release studies.
PMID- 27491361
TI - Efficacy of night-time compression for breast cancer related lymphedema (LYNC):
protocol for a multi-centre, randomized controlled efficacy trial.
AB - BACKGROUND: Lymphedema is a prevalent long-term effect of breast cancer treatment
that is associated with reduced quality of life. More recent observational data
suggest that the addition of night-time compression to day-time use of a
compression garment results in better long-term control of arm lymphedema. The
primary objectives of the randomized controlled phase of the trial are to
determine the efficacy of night-time compression on arm lymphedema volume
maintenance and quality of life in breast cancer survivors who have completed
intensive reduction treatment for their lymphedema. METHODS/DESIGN: The study
will be a parallel 3-arm, multi-centre randomized fast-track trial. A total of
120 women with breast cancer related lymphedema will be recruited from 3 centres
in Canada and randomized to group 1: Day-time compression garment alone or Group
2: Day-time compression garment + night-time compression bandaging or Group 3:
Day-time compression garment + use of a night-time compression system garment.
The duration of the primary intervention period will be 12 weeks. The follow-up
period after the intervention (weeks 13 to 24) will follow a longitudinal
observational design. The primary outcome variables: differences from baseline to
week 12 in arm volume and quality of life (Lymphoedema Functioning, Disability
and Health Questionnaire: Lymph-ICF). Secondary outcomes include bioimpedance
analysis, sleep disturbance and self-efficacy. All measurements are standardized
and will be performed prior to randomization, and at weeks 6, 12, 18 and 24.
DISCUSSION: The use of night-time compression as a self-management strategy for
chronic breast cancer related lymphedema is seen as an innovative approach to
improve long-term control over the condition. This trial aims to advance the
knowledge on self-management strategies for lymphedema. TRIAL REGISTRATION: This
trial was registered at clinicaltrials.gov on July 9(th), 2014 ( NCT02187289 ).
PMID- 27491363
TI - Seasonal and spatial variations of water quality and trophic status in Daya Bay,
South China Sea.
AB - Coastal water quality and trophic status are subject to intensive environmental
stress induced by human activities and climate change. Quarterly cruises were
conducted to identify environmental characteristics in Daya Bay in 2013. Water
quality is spatially and temporally dynamic in the bay. Cluster analysis (CA)
groups 12 monitoring stations into two clusters. Cluster I consists of stations
(S1, S2, S4-S7, S9, and S12) located in the central, eastern, and southern parts
of the bay, representing less polluted regions. Cluster II includes stations (S3,
S8, S10, and S11) located in the western and northern parts of the bay,
indicating the highly polluted regions receiving a high amount of wastewater and
freshwater discharge. Principal component analysis (PCA) identified that water
quality experience seasonal change (summer, winter, and spring-autumn seasons)
because of two monsoons in the study area. Eutrophication in the bay is graded as
high by Assessment of Estuarine Trophic Status (ASSETS).
PMID- 27491364
TI - An integrative biomarker approach to assess the environmental stress in the north
coast of Shandong Peninsula using native oysters, Crassostrea gigas.
AB - An integrative biomarker approach was employed to evaluate the environmental
quality of the north coast of Shandong Peninsula along the southern Bohai Sea of
China, where pollution is an imminent threat due to rapid urbanization and
industrialization. A battery of biomarkers and the metal bioaccumulation in
tissues of native oyster Crassostrea gigas were measured under field conditions.
Integrative biomarker index (IBR) and metal body burden were calculated to
differentiate the pollution status of seven sampling sites. According to our
results, Xinzhuang (XZ) site was the most severely contaminated, with the highest
IBR value of 3.58, while the lowest IBR value (0.04) was obtained at Penglai
(PL). Such an integrated biomarker approach was proved as a useful method for
environmental quality assessment in the study area.
PMID- 27491365
TI - Anthropogenic microfibres pollution in marine biota. A new and simple methodology
to minimize airborne contamination.
AB - Research studies on the effects of microlitter on marine biota have become more
and more frequent the last few years. However, there is strong evidence that
scientific results based on microlitter analyses can be biased by contamination
from air transported fibres. This study demonstrates a low cost and easy to apply
methodology to minimize the background contamination and thus to increase results
validity. The contamination during the gastrointestinal content analysis of 400
fishes was tested for several sample processing steps of high risk airborne
contamination (e.g. dissection, stereomicroscopic analysis, and chemical
digestion treatment for microlitter extraction). It was demonstrated that, using
our methodology based on hermetic enclosure devices, isolating the working areas
during the various processing steps, airborne contamination reduced by 95.3%. The
simplicity and low cost of this methodology provide the benefit that it could be
applied not only to laboratory but also to field or on board work.
PMID- 27491366
TI - Distribution and contamination of heavy metals in surface sediments of the Daya
Bay and adjacent shelf, China.
AB - Heavy metal (arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), mercury
(Hg), lead (Pb), and zinc (Zn)) concentrations from the Daya Bay and adjacent
shelf were determined to evaluate their levels and spatial distributions. The
measured concentrations ranged from 1.94-13.67mg/kg for As, 0.03-0.13mg/kg for
Cd, 10-85mg/kg for Cr, 1-39.5mg/kg for Cu, 0.01-0.09mg/kg for Hg, 11-56mg/kg for
Pb, and 13-125mg/kg for Zn. The spatial distributions exhibited a gradual
decrease from west to east, and the concentrations of the seven heavy metals met
the China Marine Sediment Quality criteria. Both metal enrichment factor (EF) and
geo-accumulation index (Igeo) values showed that Cd, Cr, Cu, Hg, and Zn were not
at pollution levels in the region. Multivariate analysis (PCA) revealed that
lithogenic factors dominated the distribution of most of the metals, whereas As
and Hg were clearly influenced by anthropogenic input.
PMID- 27491367
TI - A novel biomarker for marine environmental pollution of HSP90 from Mytilus
coruscus.
AB - Heat shock protein 90 (HSP90) is a conserved molecular chaperone contributing to
cell cycle control, organism development and the proper regulation of cytosolic
proteins. The full-length HSP90 cDNA of Mytilus coruscus (McHSP90, KT946644) was
2420bp, including an ORF of 2169bp encoding a polypeptide of 722 amino acids with
predicted pI/MW 4.89/83.22kDa. BLASTp analysis and phylogenetic relationship
strongly suggested McHSP90 was a member of HSP90 family, and it was highly
conserved with other known HSP90, especially in the HSP90 family signatures,
ATP/GTP-Binding sites and 'EEVD' motif. The mRNA of McHSP90 in haemolymph was
upregulated in all treatments including Vibrio alginolyticus and Vibrio harveyi
challenge, metals stresses (copper and cadmium) and 180 CST fuel exposure. All
the results implied the expression of McHSP90 could be affected by Vibrio
challenge and environmental stress, which might help us gain more insight into
the molecular mechanism of HSP against adverse stresses in mollusca.
PMID- 27491368
TI - Suspended micro-sized PVC particles impair the performance and decrease survival
in the Asian green mussel Perna viridis.
AB - Marine bivalves are known to ingest microplastics, but information on the
consequences for their physiological performance is limited. To investigate a
potential exposure pathway that has not yet been addressed, we mimicked the
resuspension of microplastics from the sediment in a laboratory exposure
experiment. For this, we exposed the Asian green mussel Perna viridis to 4
concentrations (0mg/l, 21.6mg/l, 216mg/l, 2160mg/l) of suspended
polyvinylchloride (PVC) particles (1-50MUm) for two 2-hour-time-periods per day.
After 44days, mussel filtration and respiration rates as well as byssus
production were found to be a negative function of particle concentration.
Furthermore, within 91days of exposure, mussel survival declined with increasing
PVC abundance. These negative effects presumably go back to prolonged periods of
valve closure as a reaction to particle presence. We suggest that microplastics
constitute a new seston component that exerts a stress comparable to natural
suspended solids.
PMID- 27491369
TI - An unusual case of uterine cotyledonoid dissecting leiomyoma with adenomyosis.
AB - BACKGROUND: Cotyledonoid dissecting leiomyoma is a rare variant of uterine smooth
muscle tumor with an unusual growth pattern that shows intramural dissection
within uterine myometrium and often a placenta-like appearance in its
extrauterine components. CASE PRESENTATION: We present a unique case of
cotyledonoid dissecting leiomyoma with adenomyosis. A 40-year-old Japanese female
presented with prolonged menorrhagia and severe anemia. She had a pelvic mass
followed-up for 6 years with a diagnosis of leiomyoma. However, increase in tumor
size and cystic changes with hemorrhage were found by magnetic resonance imaging,
and total abdominal hysterectomy with bilateral salpingectomy was performed.
Macroscopically, the placenta-like exophytic mass protruding from the posterior
uterine wall was composed of multiple nodules containing numerous hemorrhagic
cysts. The mass showed continuity as a white multinodular dissecting mass
infiltrating the posterolateral myometrium. Microscopically, both extra-and
intrauterine portions of the mass were composed of nodules that contained swirled
neoplastic smooth muscle cells with marked hyalinized degeneration, as observed
in cotyledonoid dissecting leiomyomas of conventional type. In addition, numerous
non-neoplastic glands of endometrial type surrounded by abundant endometrium-like
stromal cells and non-neoplastic smooth muscle cells were found in the tumor,
suggesting that it involved a part of concomitant adenomyosis originating from
the nontumoral myometrium. CONCLUSIONS: Thus far, over 30 cases of cotyledonoid
dissecting leiomyoma have been reported, none of which have described the
presence of adenomyosis within the tumor. The present case suggested that
cotyledonoid dissecting leiomyoma might have a unique clinical presentation
involving concomitant uterine adenomyosis. It is critical for pathologists,
gynecologists, and radiologists to be cognizant of cotyledonoid dissecting
leiomyoma variants for timely and appropriate diagnosis and treatment.
PMID- 27491370
TI - Search for a new economic optimum in the management of household waste in Tiaret
city (western Algeria).
AB - In household waste matters, the objective is always to conceive an optimal
integrated system of management, where the terms 'optimal' and 'integrated' refer
generally to a combination between the waste and the techniques of treatment,
valorization and elimination, which often aim at the lowest possible cost. The
management optimization of household waste using operational methodologies has
not yet been applied in any Algerian district. We proposed an optimization of the
valorization of household waste in Tiaret city in order to lower the total
management cost. The methodology is modelled by non-linear mathematical equations
using 28 variables of decision and aims to assign optimally the seven components
of household waste (i.e. plastic, cardboard paper, glass, metals, textiles,
organic matter and others) among four centres of treatment [i.e. waste to energy
(WTE) or incineration, composting (CM), anaerobic digestion (ANB) or
methanization and landfilling (LF)]. The analysis of the obtained results shows
that the variation of total cost is mainly due to the assignment of waste among
the treatment centres and that certain treatment cannot be applied to household
waste in Tiaret city. On the other hand, certain techniques of valorization have
been favoured by the optimization. In this work, four scenarios have been
proposed to optimize the system cost, where the modelling shows that the mixed
scenario (the three treatment centres CM, ANB, LF) suggests a better combination
of technologies of waste treatment, with an optimal solution for the system (cost
and profit).
PMID- 27491371
TI - Exploring social and infrastructural factors affecting open burning of municipal
solid waste (MSW) in Indian cities: A comparative case study of three
neighborhoods of Delhi.
AB - Open municipal solid waste (MSW)-burning is a major source of particulate matter
emissions in developing world cities. Despite a legal ban, MSW-burning is
observed ubiquitously in Indian cities with little being known about the factors
shaping it. This study seeks to uncover social and infrastructural factors that
affect MSW-burning at the neighborhood level. We couple physical assessments of
the infrastructure provision and the MSW-burning incidences in three different
neighborhoods of varying socio-economic status in Delhi, with an accompanying
study of the social actors (interviews of waste handlers and households) to
explore the extent to which, and potential reasons why, MSW-burning occurs. The
observed differences in MSW-burning incidences range from 130 km-2 day-1 in low
income to 30 km-2 day-1 in the high-income areas. However, two high-income areas
neighborhoods with functional infrastructure service also showed statistical
differences in MSW-burning incidences. Our interviews revealed that, while the
waste handlers were aware of the health risks associated with MSW-burning, it was
not a high priority in the context of the other difficulties they faced. The
awareness of the legal ban on MSW-burning was low among both waste handlers and
households. In addition to providing infrastructure for waste pickup, informal
restrictions from residents and neighborhood associations can play a significant
role in restricting MSW-burning at the neighborhood scale. A more efficient
management of MSW requires a combined effort that involves interplay of both
social and infrastructural systems.
PMID- 27491372
TI - Optimizing emissions targets for residential recycling programmes: Why 'more' is
not necessarily better with respect to diversion.
AB - This study highlights the economic and environmental challenges of recycling in
Ontario, specifically examining the effect of attempting to increase the
emissions target for the province's household recycling programme. The findings
from the cost model analysis found that Ontario's Blue Box programme reduces
overall carbon emissions by approximately 1.8 million tonnes every year. This
study also found that targeting specific materials for recovery could result in a
scenario where the province could improve both overall diversion and emissions
offsets while reducing material management costs. Under our modelled scenario, as
the tonnes of greenhouse gases (GHGs) avoided increases, the system cost per
tonne of GHG avoided initial declines. However, after avoiding 2.05 million
tonnes of GHGs, the system cost/tonne GHG avoided increases. To achieve an
emissions target in excess of 2.05 million tonnes, the province will have to
start recycling higher cost non-core materials (composite materials, other
plastics, etc.).
PMID- 27491373
TI - Epidemiological characteristics and methodological quality of meta-analyses on
diabetes mellitus treatment: a systematic review.
AB - OBJECTIVE: Well-conducted meta-analyses (MAs) are considered as one of the best
sources of clinical evidence for treatment decision. MA with methodological flaws
may introduce bias and mislead evidence users. The aim of this study is to
investigate the characteristics and methodological quality of MAs on diabetes
mellitus (DM) treatments. DESIGN: Systematic review. METHODS: Cochrane Database
of Systematic Review and Database of Abstract of Reviews of Effects were searched
for relevant MAs. Assessing methodological quality of systematic reviews (AMSTAR)
tool was used to evaluate the methodological quality of included MAs. Logistic
regression analysis was used to identify association between characteristics of
MA and AMSTAR results. RESULTS: A total of 252 MAs including 4999 primary studies
and 13,577,025 patients were included. Over half of the MAs (65.1%) only included
type 2 DM patients and 160 MAs (63.5%) focused on pharmacological treatments.
About 89.7% MAs performed comprehensive literature search and 89.3% provided
characteristics of included studies. Included MAs generally had poor performance
on the remaining AMSTAR items, especially in assessing publication bias (39.3%),
providing lists of studies (19.0%) and declaring source of support
comprehensively (7.5%). Only 62.7% MAs mentioned about harm of interventions. MAs
with corresponding author from Asia performed less well in providing MA protocol
than those from Europe. CONCLUSIONS: Methodological quality of MA on DM
treatments was unsatisfactory. There is considerable room for improvement,
especially in assessing publication bias, providing lists of studies and
declaring source of support comprehensively. Also, there is an urgent need for MA
authors to report treatment harm comprehensively.
PMID- 27491374
TI - Limited value for urinary 5-HIAA excretion as prognostic marker in
gastrointestinal neuroendocrine tumours.
AB - OBJECTIVE: To determine if urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion
is of prognostic value for overall survival (OS) in patients with a
gastrointestinal neuroendocrine tumour (NET) and to compare the prognostic value
with patient characteristics, ENETS/WHO grading, ENETS TNM staging and
biomarkers. DESIGN AND METHODS: Data was collected from patients with a
gastrointestinal NET or a NET with gastrointestinal metastases and available 5
HIAA excretion in 24-h urine samples. Laboratory results were stratified for
urinary 5-HIAA and chromogranin A (CgA): <2* upper limit of normal (ULN), 2-10*
ULN, or >10* ULN. For neuron-specific enolase (NSE), this was the reference range
or >1* ULN. OS was compared using Kaplan-Meier and log-rank tests, and hazard
ratios were calculated using Cox regression for univariate and multivariate
analyses. RESULTS: A total of 371 patients were included, 46.6% female with a
mean age of 59.9 years. OS was shortest in patients with urinary 5-HIAA excretion
>10* ULN vs reference range (median 83 months vs 141 months, P = 0.002). In
univariate analysis, urinary 5-HIAA excretion >10* ULN was a negative predictor
(HR 1.62, 95% CI: 1.09-2.39). However, in multivariate analysis, only age (HR
1.04, 95% CI: 1.01-1.08), grade 3 disease (HR 5.09, 95% CI: 2.20-11.79), NSE >1*
ULN (HR 2.36, 95% CI: 1.34-4.14) and CgA >10* ULN (HR 3.61, 95% CI: 1.56-8.34)
remained as the predictors. CONCLUSION: Urinary 5-HIAA excretion >10* ULN is a
negative predictor for OS. However, when added to other biomarkers and grading,
it is no longer a predictor for OS. Therefore, it should only be determined to
assess carcinoid syndrome and not for prognostic value.
PMID- 27491375
TI - Biomarkers of subclinical inflammation and increases in glycaemia, insulin
resistance and beta-cell function in non-diabetic individuals: the Whitehall II
study.
AB - OBJECTIVE: Higher systemic levels of pro-inflammatory biomarkers and low
adiponectin are associated with increased risk of type 2 diabetes, but their
associations with changes in glycaemic deterioration before onset of diabetes are
poorly understood. We aimed to study whether inflammation-related biomarkers are
associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity
and beta-cell function before the diagnosis of type 2 diabetes and whether these
associations may be bidirectional. DESIGN AND METHODS: We used multiple repeat
measures (17 891 person-examinations from 7683 non-diabetic participants) from
the Whitehall II study to assess whether circulating high-sensitivity C-reactive
protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and
adiponectin are associated with subsequent changes in glycaemia, insulin, insulin
resistance and beta-cell function (based on oral glucose tolerance tests). We
examined bidirectionality by testing if parameters of glucose metabolism at
baseline are associated with changes in inflammation-related biomarkers. RESULTS:
Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin
resistance and, for IL6, with beta-cell function after adjustment for
confounders. Higher adiponectin was associated with decreases in fasting glucose,
HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse
approach showed that 2-h glucose and insulin sensitivity were associated with
changes in IL1Ra. Fasting insulin and insulin resistance showed inverse
associations with changes in adiponectin. CONCLUSIONS: Subclinical inflammation
is associated with development of increased glycaemia, insulin resistance and
beta-cell function in non-diabetic individuals. These findings are consistent
with the hypothesis that inflammation-related processes may increase insulin
resistance and lead to a compensatory upregulation of beta-cell function.
PMID- 27491376
TI - Exploring the Interactions of the Dietary Plant Flavonoids Fisetin and Naringenin
with G-Quadruplex and Duplex DNA, Showing Contrasting Binding Behavior:
Spectroscopic and Molecular Modeling Approaches.
AB - Guanine-rich sequences have the propensity to fold into a four-stranded DNA
structure known as a G-quadruplex (G4). G4 forming sequences are abundant in the
promoter region of several oncogenes and become a key target for anticancer drug
binding. Here we have studied the interactions of two structurally similar
dietary plant flavonoids fisetin and naringenin with G4 as well as double
stranded (duplex) DNA by using different spectroscopic and modeling techniques.
Our study demonstrates the differential binding ability of the two flavonoids
with G4 and duplex DNA. Fisetin more strongly interacts with parallel G4
structure than duplex DNA, whereas naringenin shows stronger binding affinity to
duplex rather than G4 DNA. Molecular docking results also corroborate our
spectroscopic results, and it was found that both of the ligands are stacked
externally in the G4 DNA structure. C-ring planarity of the flavonoid structure
appears to be a crucial factor for preferential G4 DNA recognition of flavonoids.
The goal of this study is to explore the critical effects of small differences in
the structure of closely similar chemical classes of such small molecules
(flavonoids) which lead to the contrasting binding properties with the two
different forms of DNA. The resulting insights may be expected to facilitate the
designing of the highly selective G4 DNA binders based on flavonoid scaffolds.
PMID- 27491377
TI - Efficacy of zinc supplementation on serum calprotectin, inflammatory cytokines
and outcome in neonatal sepsis - a randomized controlled trial.
AB - OBJECTIVE: To find out the efficacy of zinc supplementation in decreasing the
levels of serum calprotectin and inflammatory cytokines with improvement in
outcome in neonatal sepsis. METHODS: Neonates with clinical signs suggestive of
sepsis and at least two screening tests positive were randomized into two groups
zinc group and control group. The zinc group received 3 mg/kg of zinc sulfate
monohydrate twice a day orally for 10 days along with antibiotics. The control
group received antibiotics and supportive care. Serum zinc, calprotectin, TNF
alpha and IL-6 were estimated in serum at recruitment and 10 days later after
completion of antibiotics. The babies were monitored daily till discharge and
mortality rate was compared between the groups. RESULTS: Baseline characteristics
were similar between the groups. Serum zinc levels were considerably increased in
the zinc group after supplementation. There was significant decline in
concentrations of serum calprotectin, TNF-alpha and IL-6 (p < 0.05) in the zinc
group. In the control group also, serum calprotectin and IL-6 levels were found
to be decreased significantly after antibiotic treatment (p < 0.05), while TNF
alpha showed insignificant reduction. Kaplan-Meier analysis was performed to
assess the survival time between the groups. The mortality was lower in the zinc
group compared to the control group 5 versus 11, p= 0.12. CONCLUSION: Neonates
with sepsis who received zinc in addition to antibiotics showed significant
reduction in serum calprotectin and inflammatory cytokines. Although mortality
was lower in zinc group, it was not statistically significant.
PMID- 27491378
TI - Active recovery of the finger flexors enhances intermittent handgrip performance
in rock climbers.
AB - This study aimed to (1) evaluate the effect of hand shaking during recovery
phases of intermittent testing on the time-force characteristics of performance
and muscle oxygenation, and (2) assess inter-individual variability in the time
to achieve the target force during intermittent testing in rock climbers. Twenty
two participants undertook three finger flexor endurance tests at 60% of their
maximal voluntary contraction until failure. Performances of a sustained
contraction and two intermittent contractions, each with different recovery
strategies, were analysed by time-force parameters and near-infrared
spectroscopy. Recovery with shaking of the forearm beside the body led to a
significantly greater intermittent test time (? 22%, P < .05), force-time
integral (? 28%, P < .05) and faster muscle re-oxygenation (? 32%, P < .05), when
compared to the hand over hold condition. Further, the ratio of intermittent to
continuous test time distinguished specific aerobic muscular adaptations among
sport climbers (2.02), boulderers (1.74) and lower grade climbers (1.25). Lower
grade climbers and boulderers produced shorter duration contractions due to the
slower development of target force during the intermittent test, indicating worse
kinaesthetic differentiation. Both the type of recovery and climbing discipline
determined muscle re-oxygenation and intermittent performance in rock climbers.
PMID- 27491379
TI - Preparation and evaluation of novel hydrogel based on polysaccharide isolated
from Bletilla striata.
AB - Natural polysaccharides are highly valued and extensively applied in drug
delivery system for their desirable physical properties and unique bioactivities.
In this work, natural polysaccharides from Bletilla striata (BSP) were
successfully extracted and incorporated with Carbopol 940 to prepare hydrogels.
Rheological behavior, skin permeation properties and bioactivities of the BSP
hydrogels were evaluated. The rheological test showed the better viscoelasticity
and physical strength of BSP gels from Carbopol gel. The scanning laser confocal
microscope (CLSM) and the trans-epidermal water loss (TEWL) examinations
indicated that the BSP hydrogels significantly improved skin permeability. The
improvement directly related with the BSP concentration in the gels. Atomic force
microscope (AFM) examinations revealed that the BSP hydrogels modified the
surface properties of corneocytes and resulted in the promotion effect.
Furthermore, bioactivity evaluations indicated the hemostatic activates of BSP
hydrogels. In conclusion, this work demonstrates the skin permeation enhancement
and plasma coagulation effects of BSP hydrogels, which show great potential in
transdermal drug delivery system and wound dressing.
PMID- 27491380
TI - Phycobiliproteins: A Novel Green Tool from Marine Origin Blue-Green Algae and Red
Algae.
AB - Marine species are comprising about a half of the whole global biodiversity; the
sea offers an enormous resource for novel bioactive compounds. Several of the
marine origin species show multifunctional bioactivities and characteristics that
are useful for a discovery and/or reinvention of biologically active compounds.
For millennia, marine species that includes cyanobacteria (blue-green algae) and
red algae have been targeted to explore their enormous potential candidature
status along with a wider spectrum of novel applications in bio- and non-bio
sectors of the modern world. Among them, cyanobacteria are photosynthetic
prokaryotes, phylogenetically a primitive group of Gramnegative prokaryotes,
ranging from Arctic to Antarctic regions, capable of carrying out photosynthesis
and nitrogen fixation. In the recent decade, a great deal of research attention
has been paid on the pronouncement of bio-functional proteins along with novel
peptides, vitamins, fine chemicals, renewable fuel and bioactive compounds, e.g.,
phycobiliproteins from marine species, cyanobacteria and red algae.
Interestingly, they are extensively commercialized for natural colorants in food
and cosmetics, antimicrobial, antioxidant, anti-inflammatory, neuroprotective,
hepatoprotective agents and fluorescent neo-glycoproteins as probes for single
particle fluorescence imaging fluorescent applications in clinical and
immunological analysis. However, a comprehensive knowledge and technological base
for augmenting their commercial utilities are lacking. Therefore, this paper will
provide an overview of the phycobiliproteins-based research literature from
marine cyanobacteria and red algae. This review is also focused towards analyzing
global and commercial activities with application oriented-based research.
Towards the end, the information is also given on the potential biotechnological
and biomedical applications of phycobiliproteins.
PMID- 27491381
TI - Marine-Derived Bioactive Peptides for Biomedical Sectors: A Review.
AB - Marine-based resources such as algae and other marine by-products have been
recognized as rich sources of structurally diverse bioactive peptides. Evidently,
their structural characteristics including unique amino acid residues are
responsible for their biological activity. Several of the above-mentioned marine
origin species show multi-functional bioactivities that are useful for a new
discovery and/or reinvention of biologically active ingredients, nutraceuticals
and/or pharmaceuticals. Therefore, in recent years, marine-derived bioactive
peptides have gained a considerable attention with high-value biomedical and/or
pharmaceutical potentials. Furthermore, a wider spectrum of bioactive peptides
can be produced through proteolytic-assisted hydrolysis of various marine
resources under controlled physicochemical (pH and temperature of the reaction
media) environment. Owing to their numerous health-related beneficial effects and
therapeutic potential in the treatment and/or prevention of many diseases, such
marine-derived bioactive peptides exhibit a wider spectrum of biological
activities such as anti-cancerous, anti-proliferative, anti-coagulant,
antibacterial, antifungal, and anti-tumor activities among many others. Based on
emerging evidence of marine-derived peptide mining, the above-mentioned marine
resources contain noteworthy levels of high-value protein. The present review
article mainly summarizes the marine-derived bioactive peptides and emphasizing
their potential applications in biomedical and/or pharmaceutical sectors of the
modern world. In conclusion, recent literature has provided evidence that marine
derived bioactive peptides play a critical role in human health along with many
possibilities of designing new functional nutraceuticals and/or pharmaceuticals
to clarify potent mechanisms of action for a wider spectrum of diseases.
PMID- 27491382
TI - Acupuncture for amnestic mild cognitive impairment: a meta-analysis of randomised
controlled trials.
AB - OBJECTIVE: Mild cognitive impairment (MCI) is a pre-dementia state; 5-10% of
cases per year will evolve into dementia. MCI can be amnestic (AMCI) or non
amnestic. AMCI is associated with a higher risk of progression. In recent years,
interest in acupuncture as a potential treatment for AMCI has grown. The aim of
this meta-analysis was to estimate the clinical effectiveness and safety of
acupuncture for AMCI. METHODS: Randomised controlled trials (RCTs) of acupuncture
versus medical treatment for AMCI were identified using the following databases
from inception to July 2015: PubMed; Medline; CENTRAL; Chinese Scientific Journal
Database; The Chinese Acupuncture Trials Register; China National Knowledge
Infrastructure (CNKI); and Wanfang database. Data were extracted from RCTs
meeting the inclusive criteria according to Cochrane methods. Meta-analyses were
conducted using Rev Man V.5.3 software. RESULTS: Five trials involving 568
subjects were included. Meta-analysis showed that participants receiving
acupuncture had better outcomes than those receiving nimodipine with greater
clinical efficacy rates (odds ratio (OR) 1.78, 95% CI 1.19 to 2.65; p<0.01), mini
mental state examination (MMSE) scores (mean difference (MD) 0.99, 95% CI 0.71 to
1.28; p<0.01), and picture recognition score (MD 2.12, 95% CI 1.48 to 2.75;
p<0.01). Meta-analysis also showed acupuncture in conjunction with nimodipine
significantly improved MMSE scores (MD 1.09, 95% CI 0.29 to 1.89; p<0.01)
compared to nimodipine alone. Three trials reported adverse events.
Methodological quality of the included studies was judged to be generally poor.
CONCLUSIONS: Acupuncture appears effective for AMCI when used as an alternative
or adjunctive treatment; however, caution must be exercised given the low
methodological quality of included trials. Further, more rigorously designed
studies are needed.
PMID- 27491383
TI - Nociceptin/orphanin FQ receptor gene variation is associated with smoking status
in Japanese.
AB - AIM: The endogenous opioid system has been reportedly implicated in
tobacco/nicotine dependence. MATERIALS & METHODS: We examined the genetic effects
of eight SNPs in opioid receptor-related genes on smoking status and smoking
related traits in Japanese. RESULTS: The genotypic and allelic variations of the
rs2229205 SNP in the OPRL1 gene were significantly associated with smoking
status, but no significant differences were found in the genetic variations of
any of the SNPs with regard to smoking-related traits. The rs2229205 SNP did not
show high linkage disequilibrium with the other SNPs in the linkage
disequilibrium block that contained the SNP. CONCLUSION: The rs2229205 SNP in the
OPRL1 gene may be a genetic factor that contributes to individual differences in
the vulnerability to smoking in Japanese individuals.
PMID- 27491384
TI - Newly arrived refugee children with Helicobacter pylori are thinner than their
non-infected counterparts.
AB - The hypothesis of this study was that those refugee children with Helicobacter
pylori are thinner than their non-infected counterparts. This cross-sectional
study investigated the height and weight of newly arrived refugee children up to
age 19 years, who were screened for H. pylori using a stool antigen test at the
Migrant Health Service in Adelaide between August 2010 and October 2013. Of 460
children, 21% were infected with H. pylori. After adjusting for vitamin B12 and
iron levels, ethnicity, age and sex, the odds of being thin in the 10- to 19-year
old age group was 4.28-fold higher (95% CI 1.48-12.4) if they were H. pylori
positive compared with those who were H. pylori negative. The difference between
the two groups is statistically significant (P=0.01). Screening and treatment for
H. pylori in the general population in developed countries is not recommended
unless there are symptoms such as dyspepsia or risk of peptic ulcer, duodenal
ulcer or gastric cancer. Given the findings of this study, a recommendation could
be made that newly arrived refugee children who are thin should be tested for H.
pylori. Thinness in children may influence their cognitive ability, school
performance, physical endurance and hence their ability to successfully settle
into their new country.
PMID- 27491385
TI - A multisite evaluation of summer camps for children with cancer and their
siblings.
AB - Summer camps for pediatric cancer patients and their families are ubiquitous.
However, there is relatively little research, particularly studies including more
than one camp, documenting outcomes associated with children's participation in
summer camp. The current cross-sectional study used a standardized measure to
examine the role of demographic, illness, and camp factors in predicting
children's oncology camp-related outcomes. In total, 2,114 children at 19 camps
participated. Campers were asked to complete the pediatric camp outcome measure,
which assesses camp-specific self-esteem, emotional, physical, and social
functioning. Campers reported high levels of emotional, physical, social, and
self-esteem functioning. There were differences in functioning based on
demographic and illness characteristics, including gender, whether
campers/siblings were on or off active cancer treatment, age, and number of prior
years attending camp. Results indicated that summer camps can be beneficial for
pediatric oncology patients and their siblings, regardless of demographic factors
(e.g., gender, treatment status) and camp factors (e.g., whether camp sessions
included patients only, siblings only, or both). Future work could advance the
oncology summer camp literature by examining other outcomes linked to summer camp
attendance, using longitudinal designs, and including comparison groups.
PMID- 27491386
TI - A large two-centre study in to rates of influenza and pneumococcal vaccination
and infection burden in rheumatoid arthritis in the UK.
AB - BACKGROUND: Infections are a common complication of RA with associated morbidity
and mortality. The aetiology of increased risk is complex and multifactorial.
Despite this, strategies to mitigate against risk of infection including
vaccination are not always addressed in primary or secondary care with wide
variation in practice from multiple small single centre audits. This study was a
large two-centre survey of vaccine uptake in routine clinical practice and
evaluated the relationship between vaccination and the burden of infection in RA
patients. METHODS: A patient questionnaire was devised and disseminated through
postal, clinic and phone survey at 2 UK rheumatology centres, detailing past
vaccination history, reasons for non-vaccination, and history of recent
infection. In a subset of patients, primary care vaccination data were also
obtained. RESULTS: In total 929 patients responded to the survey. Over 85 % of
patients were vaccinated against influenza, however only 44 % were vaccinated
against pneumococcus. The vast majority of vaccination was undertaken in primary
care. In the 12 months prior to the survey, 7.7 % of subjects recalled at least
one episode of severe infection requiring admission, and nearly 40 % reported
receiving at least one course of antibiotics. CONCLUSIONS: Infections are common
in RA and Rheumatologists need to be adept at recognising at risk patients and
managing them appropriately. Influenza vaccination uptake is good whilst
pneumococcal vaccination rates are comparatively poor. Collaborative approaches
between primary and secondary care are required to maximise vaccine uptake, which
is safe and recommended in RA patients.
PMID- 27491388
TI - Lung-specific RNA interference of coupling factor 6, a novel peptide, attenuates
pulmonary arterial hypertension in rats.
AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive and life
threatening disease associated with high morbidity and mortality rates. However,
the exact regulatory mechanism of PAH is unknown. Although coupling factor 6
(CF6) is known to function as a repressor, its role in PAH has not been explored.
Here, we investigated the involvement of endogenous CF6 in the development of
PAH. METHODS: PAH was induced with monocrotaline (MCT), as demonstrated by
significant increases in pulmonary artery pressure and vessel wall thickness. The
adeno-associated virus (AAV) carrying CF6 short hairpin RNA (shRNA) or control
vector (2*10(10) gp) was intratracheally transfected into the lungs of rats 2
weeks before or after MCT injection. RESULTS: A 2-6-fold increase in CF6 was
observed in the lungs and circulation of the MCT-injected rats as confirmed by
qRT-PCR and ELISA. Immunohistochemistry analysis revealed a small quantity of CF6
localized to endothelial cells (ECs) under physiological conditions spread to
surrounding tissues in a paracrine manner in PAH lungs. Notably, CF6 shRNA
effectively inhibited CF6 expression, abolished lung macrophage infiltration,
reversed endothelial dysfunction and vascular remodeling, and ameliorated the
severity of pulmonary hypertension and right ventricular dysfunction at 4 weeks
both as a pretreatment and rescue intervention. In addition, the circulating and
lung levels of 6-keto-PGF1a, a stable metabolite of prostacyclin, were reversed
by CF6 inhibition, suggesting that the effect of CF6 inhibition may partly be
mediated through prostacyclin. CONCLUSIONS: CF6 contributes to the pathogenesis
of PAH, probably in association with downregulation of prostacyclin. The blockage
of CF6 might be applied as a novel therapeutic approach for PAH and PA
remodeling.
PMID- 27491390
TI - The wizard behind the curtain: programmers as providers.
AB - It is almost universally accepted that traditional provider-patient relationships
should be governed, at least in part, by the ethical principles set forth by
Beauchamp and Childress (Beauchamp and Childress, Principles of biomedical
ethics, 1979). These principles include autonomy, beneficence, non-maleficence
and justice (Beauchamp and Childress, Principles of biomedical ethics, 1979).
Recently, however, the nature of medial practice has changed. The pervasive
presence of computer technology in medicine raises interesting ethical questions.
In this paper we argue that some software designers should be considered health
care providers and thus be subject the ethical principles incumbent upon
"traditional" providers. We argue that these ethical responsibilities should be
applied explicitly rather than as a passive, implicit, set of guidelines.
PMID- 27491387
TI - A practical community-based response strategy to interrupt Ebola transmission in
sierra Leone, 2014-2015.
AB - BACKGROUND: The Ebola virus disease spread rapidly in West Africa in 2014,
leading to the loss of thousands of lives. Community engagement was one of the
key strategies to interrupt Ebola transmission, and practical community level
measures needed to be explored in the field and tailored to the specific context
of communities. METHODS: First, community-level education on Ebola virus disease
(EVD) prevention was launched for the community's social mobilizers in six
districts in Sierra Leone beginning in November 2014. Then, from January to May
of 2015, in three pilot communities, local trained community members were
organized to engage in implementation of EVD prevention and transmission
interruption measures, by involving them in alert case report, contact tracing,
and social mobilization. The epidemiological indicators of transmission
interruption in three study communities were evaluated. RESULTS: A total of 6 016
community social mobilizers from 185 wards were trained by holding 279 workshops
in the six districts, and EVD message reached an estimated 631 680 residents. In
three pilot communities, 72 EVD alert cases were reported, with 70.8 % of them
detected by trained local community members, and 14 EVD cases were finally
identified. Contact tracing detected 64.3 % of EVD cases. The median duration of
community infectivity for the cases was 1 day. The secondary attack rate was 4.2
%, and no third generation of infection was triggered. No health worker was
infected, and no unsafe burial and noncompliance to EVD control measures were
recorded. The community-based measures were modeled to reduce 77 EVD cases, and
the EVD-free goal was achieved four months earlier in study communities than
whole country of Sierra Leone. CONCLUSIONS: The community-based strategy of
social mobilization and community engagement was effective in case detection and
reducing the extent of Ebola transmission in a country with weak health system.
The successfully practical experience to reduce the risk of Ebola transmission in
the community with poor resources would potentially be helpful for the global
community to fight against the EVD and the other diseases in the future.
PMID- 27491391
TI - All-optical transistor- and diode-action and logic gates based on anisotropic
nonlinear responsive liquid crystal.
AB - In this paper, we show that anisotropic photosensitive nematic liquid crystals
(PNLC) made by incorporating anisotropic absorbing dyes are promising candidates
for constructing all-optical elements by virtue of the extraordinarily large
optical nonlinearity of the nematic host. In particular, we have demonstrated
several room-temperature 'prototype' PNLC-based all-optical devices such as
optical diode, optical transistor and all primary logic gate operations (OR, AND,
NOT) based on such optical transistor. Owing to the anisotropic absorption
property and the optical activity of the twist alignment nematic cell, spatially
non-reciprocal transmission response can be obtained within a sizeable optical
isolation region of ~210 mW. Exploiting the same mechanisms, a tri-terminal
configuration as an all-optical analogue of a bipolar junction transistor is
fabricated. Its ability to be switched by an optical field enables us to realize
an all-optical transistor and demonstrate cascadability, signal fan-out, logic
restoration, and various logical gate operations such as OR, AND and NOT. Due to
the possibility of synthesizing anisotropic dyes and wide ranging choice of
liquid crystals nonlinear optical mechanisms, these all-optical operations can be
optimized to have much lower thresholds and faster response speeds. The
demonstrated capabilities of these devices have shown great potential in all
optical control system and photonic integrated circuits.
PMID- 27491389
TI - Statin use and breast cancer survival: a nationwide cohort study in Scotland.
AB - BACKGROUND: Preclinical evidence suggests that statins could delay cancer
progression. Previous epidemiological findings have been inconsistent and some
have been limited by small sample sizes, as well as certain time-related biases.
This study aimed to investigate whether breast cancer patients who were exposed
to statins had reduced breast cancer-specific mortality. METHODS: We conducted a
retrospective cohort study of 15,140 newly diagnosed invasive breast cancer
patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry.
Dispensed medication usage was obtained from linkages to the Scottish Prescribing
Information System and breast cancer-specific deaths were identified from
National Records of Scotland Death Records. Using time-dependent Cox regression
models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for
the association between post-diagnostic exposure to statins (including
simvastatin) and breast cancer-specific mortality. Adjustments were made for a
range of potential confounders including age at diagnosis, year of diagnosis,
cancer stage, grade, cancer treatments received, comorbidities, socioeconomic
status and use of aspirin. RESULTS: A total of 1,190 breast cancer-specific
deaths occurred up to January 2015. Overall, after adjustment for potential
confounders, there was no evidence of an association between statin use and
breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No
significant associations were observed in dose-response analyses or in analysis
of all-cause mortality. For simvastatin use specifically, a weak non-significant
reduction in breast cancer-specific mortality was observed compared to non-users
(adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly
associated with a reduction in breast cancer-specific mortality (adjusted HR
0.85, 95 % CI 0.74, 0.98). CONCLUSION: Overall, we found little evidence of a
protective association between post-diagnostic statin use and cancer-specific
mortality in a large nation-wide cohort of breast cancer patients. These findings
will help inform the decision whether to conduct randomised controlled trials of
statins as an adjuvant treatment in breast cancer.
PMID- 27491392
TI - Self-assembled oxide films with tailored nanoscale ionic and electronic channels
for controlled resistive switching.
AB - Resistive switches are non-volatile memory cells based on nano-ionic redox
processes that offer energy efficient device architectures and open pathways to
neuromorphics and cognitive computing. However, channel formation typically
requires an irreversible, not well controlled electroforming process, giving
difficulty to independently control ionic and electronic properties. The device
performance is also limited by the incomplete understanding of the underlying
mechanisms. Here, we report a novel memristive model material system based on
self-assembled Sm-doped CeO2 and SrTiO3 films that allow the separate tailoring
of nanoscale ionic and electronic channels at high density (~10(12) inch(-2)). We
systematically show that these devices allow precise engineering of the
resistance states, thus enabling large on-off ratios and high reproducibility.
The tunable structure presents an ideal platform to explore ionic and electronic
mechanisms and we expect a wide potential impact also on other nascent
technologies, ranging from ionic gating to micro-solid oxide fuel cells and
neuromorphics.
PMID- 27491394
TI - Self-assembled half-sandwich polyhedral cages via flexible Schiff-base ligands:
an unusual macrocycle-to-cage conversion.
AB - An edge-directed strategy was adopted to construct highly ordered polyhedral
structures using flexible functions. Half-sandwich M6(L1)4 octahedral and M8(L2)4
cubic cages have been assembled by flexible Schiff-base ligands upon coordination
to Cp*Rh(iii) organometallic acceptors. In particular, the rearrangement from a
Rh(iii)-based half-sandwich M2(HL1)2 macrocycle to M6(L1)4 cage was found to
occur in a solution.
PMID- 27491393
TI - Global Expressions Landscape of NAC Transcription Factor Family and Their
Responses to Abiotic Stresses in Citrullus lanatus.
AB - Watermelon (Citrullus lanatus) is one xerophyte that has relative higher
tolerance to drought and salt stresses as well as more sensitivity to cold
stress, compared with most model plants. These characteristics facilitate it a
potential model crop for researches on salt, drought or cold tolerance. In this
study, a genome-wide comprehensive analysis of the ClNAC transcription factor
(TF) family was carried out for the first time, to investigate their
transcriptional profiles and potential functions in response to these abiotic
stresses. The expression profiling analysis reveals that several NAC TFs are
highly responsive to abiotic stresses and development, for instance, subfamily IV
NACs may play roles in maintaining water status under drought or salt conditions,
as well as water and metabolites conduction and translocation toward fruit. In
contrast, rapid and negative responses of most of the ClNACs to low-temperature
adversity may be related to the sensitivity to cold stress. Crosstalks among
these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways
were also discussed based on the expression of ClNAC genes. Our results will
provide useful insights for the functional mining of NAC family in watermelon, as
well as into the mechanisms underlying abiotic tolerance in other cash crops.
PMID- 27491395
TI - Chiral recognition at self-assembled multivalent (SAMul) nanoscale interfaces -
enantioselectivity in polyanion binding.
AB - Self-assembled multivalent (SAMul) ligands based on palmitic acid functionalised
with cationic l/d-lysine bind polyanionic heparin or DNA with no chiral
preference. Inserting a glycine spacer unit switches on chiral discrimination - a
rare example of controlled chiral recognition at a SAMul nanoscale interface.
PMID- 27491398
TI - Electrocatalytic Efficiency Analysis of Catechol Molecules for NADH Oxidation
during Nanoparticle Collision.
AB - Electrocatalysis of molecules is a hot research topic in biological and energy
related chemistry. Here, we develop a new system to study the electrocatalytic
efficiency of a single catechol molecule for NADH oxidation by single
functionalized nanoparticle collision at ultramicroelectrodes (UMEs). The
proposed system is composed of gold nanoparticles (AuNPs) functionalized with
catechol molecules and a carbon-fiber ultramicroelectrode. In the absence of
NADH, when a functionalized AuNP collides with an UME at a suitable voltage, a
small current spike is generated due to the oxidation of catechol molecules
modified on the surface of AuNP. In the presence of NADH, the current spike is
significantly amplified by the combined effects of the oxidation and
electrocatalysis for NADH of catechol molecules. By analyzing the variations of
the average peak charges and durations without or with NADH, we calculate that
around five thousands NADH molecules could be catalyzed per second by a single
catechol molecule, suggesting the successful establishment of this novel
catalytic system. Thus, the proposed strategy could be used as a promising
platform for research of other molecular electrocatalytic systems.
PMID- 27491396
TI - Risk Score for Predicting Treatment-Requiring Retinopathy of Prematurity (ROP) in
the Telemedicine Approaches to Evaluating Acute-Phase ROP Study.
AB - PURPOSE: To develop a risk score for predicting treatment-requiring retinopathy
of prematurity (TR-ROP) in the Telemedicine Approaches to Evaluating Acute-Phase
Retinopathy of Prematurity (e-ROP) study. DESIGN: Second analyses of an
observational cohort study. PARTICIPANTS: Infants with birth weight (BW) <1251 g
who had >=1 imaging session by 34 weeks of postmenstrual age (PMA) and >=1
subsequent retinopathy of prematurity (ROP) examination for determining TR-ROP by
study-certified ophthalmologists. METHODS: Nonphysician trained readers evaluated
wide-field retinal image sets for characteristics of ROP, pre-plus/plus disease,
and retinal hemorrhage. Risk score points for predicting TR-ROP were derived from
the regression coefficients of significant predictors in a multivariate logistic
regression model. MAIN OUTCOME MEASURES: TR-ROP. RESULTS: Eighty-five of 771
infants (11.0%) developed TR-ROP. In a multivariate model, significant predictors
for TR-ROP were gestational age (GA) (odds ratio [OR], 5.7; 95% confidence
interval [CI], 1.7-18.9 for <=25 vs. >=28 weeks), need for respiratory support
(OR, 7.0; 95% CI, 1.3-37.1 for high-frequency oscillatory ventilation vs. no
respiratory support), slow weight gain (OR, 2.4; 95% CI, 1.2-4.6 for weight gain
<=12 g/day vs. >15 g/day), and image findings at the first image session
including number of quadrants with pre-plus (OR, 3.8; 95% CI, 1.5-9.7 for 4 pre
plus quadrants vs. no pre-plus), stage and zone of ROP (OR, 4.7; 95% CI, 2.1-11.8
for stage 1-2 zone I, OR, 5.9; 95% CI, 2.1-16.6 for stage 3 zone I vs. no ROP),
and presence of blot hemorrhage (OR, 3.1; 95% CI, 1.4-6.7). Image findings
predicted TR-ROP better than GA (area under receiver operating characteristic
curve [AUC] = 0.82 vs. 0.75, P = 0.03). The risk of TR-ROP steadily increased
with higher risk score and predicted TR-ROP well (AUC = 0.88; 95% CI, 0.85-0.92).
Risk score >=3 points for predicting TR-ROP had a sensitivity of 98.8%,
specificity of 40.1%, and positive and negative predictive values of 17.0% and
99.6%, respectively. CONCLUSIONS: Image characteristics at 34 PMA weeks or
earlier independently predict TR-ROP. If externally validated in other infants,
risk score, calculated from image findings, GA, weight gain, and respiratory
support, enables early identification of infants in need of increased
surveillance for TR-ROP.
PMID- 27491397
TI - Characterization of Chorioretinopathy Associated with Mitochondrial Trifunctional
Protein Disorders: Long-Term Follow-up of 21 Cases.
AB - PURPOSE: To assess long-term effects of genotype on chorioretinopathy severity in
patients with mitochondrial trifunctional protein (MTP) disorders. DESIGN:
Retrospective case series. PARTICIPANTS: Consecutive patients with MTP disorders
evaluated at a single center from 1994 through 2015, including 18 patients with
long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients
with trifunctional protein deficiency (TFPD). METHODS: Local records from all
visits were reviewed. Every participant underwent a complete ophthalmic
examination and was evaluated by a metabolic physician and dietitian. Nine
patients underwent ancillary funduscopic imaging including optical coherence
tomography (OCT) and OCT angiography. MAIN OUTCOME MEASURES: The primary outcome
measure was best-corrected visual acuity at the final visit. Secondary outcome
measures included spherical equivalent refraction, visual fields,
electroretinography B-wave amplitudes, and qualitative imaging findings. RESULTS:
Participants were followed up for a median of 5.6 years (range 0.3-20.2 years).
The median age of LCHADD participants at initial and final visits was 2.3 and
11.9 years, whereas that for TFPD participants at initial and final visits was
4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years
were included (3 with LCHADD and 1 with TFPD). The LCHADD participants
demonstrated a steady decline in visual acuity from an average of 0.23 logarithm
of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at
baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas
TFPD patients maintained excellent acuity throughout follow-up. Participants with
LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in
spherical equivalent refraction of 0.24 diopters per year. Visual fields showed
sensitivity losses centrally associated with defects on OCT. Multimodal imaging
demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by
the formation of outer retinal tubulations and choriocapillaris dropout.
Electroretinography findings support the more severe clinical profile of LCHADD
patients compared with TFPD patients; the function of both rods and cones are
attenuated diffusely in LCHADD patients, but are within normal limits for TFPD
patients. CONCLUSIONS: Despite improved survival with early diagnosis, medical
management, and dietary treatment, participants with the LCHADD subtype of MTP
disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal
imaging is most consistent with choriocapillaris loss exceeding photoreceptor
loss.
PMID- 27491399
TI - The synergy and mode of action of quercetin plus amoxicillin against amoxicillin
resistant Staphylococcus epidermidis.
AB - BACKGROUND: Staphylococcus epidermidis is one of the most multiple resistances to
antibiotics in the recent years. Therefore, practically-prescribed antibiotics in
the treatment of these strains are not effective. Plant-derived antibacterial is
one of the most interesting sources of new therapeutics. The present study was to
investigate antibacterial, synergy and modes of action of quercetin and
amoxicillin against amoxicillin-resistant Staphylococcus epidermidis (ARSE).
METHODS: The MICs, checkerboard assay, viability curves, cytoplasmic membrane
(CM) permeability, enzyme assay, transmission electron microscopy, confocal
microscopy and FT-IR microspectroscopy measurement was performed. RESULTS: The
MICs of amoxicillin, penicillin, quercetin and kaempferol against all ARSE
strains were 16, 200, 256-384 and >1024 MUg/mL respectively. Synergistic effects
were exhibited on amoxicillin plus quercetin and penicillin plus kaempferol
against these strains at FIC index 0.50 and <0.38 respectively. The synergistic
activity of quercetin plus amoxicillin was confirmed by the viable count. This
combination increased CM permeability, caused marked morphological, peptidoglycan
and cytoplasmic membrane damage, increased protein amide I and II, but decreased
fatty acid in bacterial cells. The quercetin had an inhibitory activity against
beta-lactamase. CONCLUSIONS: So, these findings are the first report that
quercetin has the synergistic effect with amoxicillin against ARSE via four modes
of actions, inhibit peptidoglycan synthesis and beta-lactamases activity,
increase CM permeability and protein amide I and II but decrease fatty acid in
bacterial cells. Of course, this flavonol has the dominant potential to develop a
brand-new collateral phytochemical agent plus amoxicillin to treat ARSE. Future
work should focus on the bioavailability, efficacy and toxicity in animal and
human studies, as well as, the synergistic effect on blood and tissue should be
evaluated and achieved.
PMID- 27491400
TI - A locking compression plate as an external fixator for treating infected nonunion
of the humeral diaphysis.
AB - BACKGROUND: Infected nonunion of the humeral diaphysis is a challenging problem
for orthopedic surgeons. This study aimed to evaluate the outcome of using a
locking compression plate (LCP) as a definitive external fixator in the
management of infected nonunion of the humeral diaphysis after failure of
internal fixation. METHODS: We retrospectively reviewed a series of seven
patients with infected nonunion of the humeral diaphysis treated with an LCP as
an external fixator between June 2010 and August 2014. There were five males and
two females, with an average age of 40.9 years. Six out of seven patients had
been definitively diagnosed with infection due to known bacteria by germiculture.
The clinical and radiographic outcomes were retrospectively evaluated. RESULTS:
All patients were followed-up for a mean period of 26.3 months (range 12-48
months). All fractures obtained complete bone union, and the average time to bone
union was 7.9 months (range 3.5-15 months). All infections were eventually
resolved without any recurrence of deep infection. Pin tract infection was only
seen in one case. Only one patient had transient radial nerve palsy after surgery
for traction. The average shortening length of the affected upper limb was 3 cm
(range 2-4 cm) compared with the contralateral limb. At the last follow-up, the
average Disabilities of the Arm, Shoulder and Hand score of the involved limbs
was 3.2 (range 0-13.4). All patients obtained excellent or good functional
results, and returned to their original work. CONCLUSIONS: The novel use of an
LCP as a definitive external fixator was an effective method for treating
infected nonunion of the humeral diaphysis. However, a large-scale prospective
clinical study is still needed to verify these findings.
PMID- 27491401
TI - Collective dynamics of identical phase oscillators with high-order coupling.
AB - In this paper, we propose a framework to investigate the collective dynamics in
ensembles of globally coupled phase oscillators when higher-order modes dominate
the coupling. The spatiotemporal properties of the attractors in various regions
of parameter space are analyzed. Furthermore, a detailed linear stability
analysis proves that the stationary symmetric distribution is only neutrally
stable in the marginal regime which stems from the generalized time-reversal
symmetry. Moreover, the critical parameters of the transition among various
regimes are determined analytically by both the Ott-Antonsen method and linear
stability analysis, the transient dynamics are further revealed in terms of the
characteristic curves method. Finally, for the more general initial condition the
symmetric dynamics could be reduced to a rigorous three-dimensional manifold
which shows that the neutrally stable chaos could also occur in this model for
particular parameters. Our theoretical analysis and numerical results are
consistent with each other, which can help us understand the dynamical properties
in general systems with higher-order harmonics couplings.
PMID- 27491402
TI - EGFR and EML4-ALK Updated Therapies in Non-Small Cell Lung Cancer.
AB - BACKGROUND: Non-small cell lung cancer is the leading cancer-related cause of
death. OBJECTIVE: We review the latest therapies for NSCLC with EGFR and ELM4-ALK
mutations as well as the most relevant studies and promising patents. METHOD: A
literature search of PubMed database was carried out to identify recent Clinical
Trials using EGFR therapies and novel patents involving diagnosis and therapies
on NSCLC. We conducted a search to find new therapy strategies, new biomarkers,
and selected five patents we find relevant. RESULTS: Over the last few years,
identification of cancer harboring epidermal growth factor receptor mutations
(EGFR) or chromosomal rearrangements of anaplastic lymphoma kinase (ALK) led to
new ways in classifying and treating NSCLC. On the other hand, acquired
resistance are a constantly challenge in the management of patients with these
mutations and new drugs options are in development to improve and amplify
treatment strategies. CONCLUSIONS: Currently, EGFR TKIs (e.g.: erlotinib,
gefitinib, osimertinib) and ALK inhibitors (crizotinib, ceritinib, alectinib)
provided a new face for advanced NSCLC outcomes. To understand the disease
molecular profile is mandatory to define the best approach for each patient.
PMID- 27491403
TI - Cactus thorn detection using bedside ultrasound.
PMID- 27491404
TI - An Assessment of the Results of European Parliament Elections in Greece and
European Union Under the Shadow of Economic Crisis.
AB - On January 1, 1981, Greece became the tenth member of the European Economic
Community and, 20 years later, on January 1, 2001, joined the euro area. In May
of 2010 and February of 2012, Greece signed the first and the second economic
adjustment programs and adopted austerity policies throughout the public sector
in order to avoid the economic collapse, affecting residents' income and health
status. We studied the questionnaires of polls conducted in Greece before the
elections of the European Parliament (May 25, 2014) and the "Europeans 2014"
Eurobarometer's survey in March of 2014. The responses of Greek voters from the
Greek polls were alarming, pointing out their declining personal economic
situation and Greece's national economic situation, with a sense that the country
was heading in the wrong direction, declaring themselves unsatisfied and
insecure. The responses of Greek voters from the "Europeans 2014" survey were
even more alarming. Health was the first priority for the voters. As the Greek
polls and the Eurobarometer's survey forecasted, but more significantly as the
results of the Euro-elections showed, Greek voters preferred to put their hopes
in something new.
PMID- 27491405
TI - Novel Use of a Pneumatic Compression Device for Haemostasis of Haemodialysis
Fistula Access Catheterisation Sites.
AB - PURPOSE: Transradial pneumatic compression devices can be used to achieve
haemostasis following radial artery puncture. This article describes a novel
technique for acquiring haemostasis of arterio-venous haemodialysis fistula
access sites without the need for suture placement using one such compression
device. MATERIALS AND METHODS: A retrospective review of fistulograms with or
without angioplasty/thrombectomy in a single institution was performed. 20
procedures performed on 12 patients who underwent percutaneous intervention of
failing or thrombosed arterio-venous fistulas (AVF) had 27 puncture sites.
Haemostasis was achieved using a pneumatic compression device at all access
sites. Procedure details including size of access sheath, heparin administration
and complications were recorded. RESULTS: Two diagnostic fistulograms, 14
fistulograms and angioplasties and four thrombectomies were performed via access
sheaths with an average size (+/-SD) of 6 Fr (+/-1.12). IV unfractionated heparin
was administered in 11 of 20 procedures. Haemostasis was achieved in 26 of 27
access sites following 15-20 min of compression using the pneumatic compression
device. One case experienced limited bleeding from an inflow access site that was
successfully treated with reinflation of the device for a further 5 min. No other
complication was recorded. CONCLUSIONS: Haemostasis of arterio-venous
haemodialysis fistula access sites can be safely and effectively achieved using a
pneumatic compression device. This is a technically simple, safe and sutureless
technique for acquiring haemostasis after AVF intervention.
PMID- 27491406
TI - Phase I/II Multi-Institutional Study of Percutaneous Radiofrequency Ablation for
Painful Osteoid Osteoma (JIVROSG-0704).
AB - PURPOSE: This multicenter prospective study was conducted to evaluate the safety
and efficacy of percutaneous radiofrequency ablation (RFA) for painful osteoid
osteoma (OO). MATERIALS AND METHODS: Patients with OO (femur: n = 17, tibia: n =
2, humerus: n = 1, rib: n = 1) were enrolled and treated with RFA. In phase I,
nine patients were evaluated for safety. In phase II, 12 patients were accrued,
and an intent-to-treat analysis was performed on all patients. The primary
endpoint was to evaluate the treatment safety. The secondary endpoint was to
evaluate the efficacy for pain relief by the visual analogue scale (VAS) at 4
weeks after RFA. Treatment efficacy was classified as significantly effective
(SE) when VAS score decreased by >=5 or score was <2, moderately effective when
VAS score decreased by <5->=2 and score was >=2, and not effective (NE) when VAS
score decreased by <2 or score was increased. Cases where the need for analgesics
increased after treatment were also NE. RESULTS: RFA procedures were completed in
all patients. Minor adverse effects (AEs) were observed as 4.8-14.3 % in 12
patients, and no major AEs were observed. Mean VAS score was 7.1 before
treatment, 1.6 at 1 week, 0.3 at 4 weeks, and 0.2 at 3 months. All procedures
were classified as SE. Pain recurrence was not noted in any patient during follow
up (mean: 15.1 months). CONCLUSION: RFA is a safe, highly effective, and fast
acting treatment for painful extraspinal OO. Future studies with a greater number
of patients are needed.
PMID- 27491407
TI - Visualization of precut DSAEK and pre-stripped DMEK donor corneas by
intraoperative optical coherence tomography using the RESCAN 700.
AB - BACKGROUND: To report the feasibility of intraoperative spectral domain optical
coherence tomography (OCT) using the RESCAN 700 for the visualization and
evaluation of precut Descemet's stripping automated endothelial keratoplasty
(DSAEK) and prestripped Descemet's membrane endothelial keratoplasty (DMEK) donor
tissue. METHODS: Precut DSAEK (n = 11), prestripped DMEK (n = 4) preserved in a
viewing chamber were examined by intraoperative OCT. Wholly intact donor corneas
for penetrating keratoplasty (PK) (n = 8) were also examined as controls. The
obtained images were analyzed qualitatively for characteristics of each type of
donor. RESULTS: For each type of donor, characteristic images were consistently
obtained by intraoperative OCT in both the front and back views through the
viewing chamber. In wholly intact donors for PK, appearance of normal corneal
curvature and stromal texture with high reflectivity of epithelium and
endothelium cell layers were clearly visualized. In precut DSAEK donors, precut
lines were characteristically visualized in addition to the intact donor cornea
images. In prestripped DMEK donors, identical OCT images to the intact donor
cornea were noted when observed from the anterior surface. However, peripheral
partial detachments of Descemet's membrane were characteristically observed in
all prestripped DMEK donors when viewed from the back of the viewing chamber.
CONCLUSION: Rapid visualization and rough evaluation of donor tissues for PK,
precut DSAEK and prestripped DMEK donor corneas by intraoperative OCT was
consistently possible through the viewing chamber. Therefore, this device may be
used as an alternative of AS-OCT when the eyebank does not have their own AS-OCT.
Although the peripheral detachment in DMEK donors are quite common and clinically
non-problematic in DMEK donor quality and subsequent DMEK surgeries, it may be
useful to distinguish between wholly intact PK donors and prestripped DMEK
donors, enabling to prevent mix-ups of donors, especially when several different
types of keratoplasties are scheduled in a same day in one operating theater.
PMID- 27491409
TI - Two-photon excited fluorescence of intrinsic fluorophores enables label-free
assessment of adipose tissue function.
AB - Current methods for evaluating adipose tissue function are destructive or have
low spatial resolution. These limit our ability to assess dynamic changes and
heterogeneous responses that occur in healthy or diseased subjects, or during
treatment. Here, we demonstrate that intrinsic two-photon excited fluorescence
enables functional imaging of adipocyte metabolism with subcellular resolution.
Steady-state and time-resolved fluorescence from intracellular metabolic co
factors and lipid droplets can distinguish the functional states of excised
white, brown, and cold-induced beige fat. Similar optical changes are identified
when white and brown fat are assessed in vivo. Therefore, these studies establish
the potential of non-invasive, high resolution, endogenous contrast, two-photon
imaging to identify distinct adipose tissue types, monitor their functional
state, and characterize heterogeneity of induced responses.
PMID- 27491410
TI - The p90 ribosomal S6 kinase 2 specifically affects mitotic progression by
regulating the basal level, distribution and stability of mitotic spindles.
AB - RSK2, also known as RPS6KA3 (ribosomal protein S6 kinase, 90 kDa, polypeptide 3),
is a downstream kinase of the mitogen-activated protein kinase (MAPK) pathway,
which is important in regulating survival, transcription, growth and
proliferation. However, its biological role in mitotic progression is not well
understood. In this study, we examined the potential involvement of RSK2 in the
regulation of mitotic progression. Interestingly, depletion of RSK2, but not
RSK1, caused the accumulation of mitotic cells. Time-lapse analysis revealed that
mitotic duration, particularly the duration for metaphase-to-anaphase transition
was prolonged in RSK2-depleted cells, suggesting activation of spindle assembly
checkpoint (SAC). Indeed, more BubR1 (Bub1-related kinase) was present on
metaphase plate kinetochores in RSK2-depleted cells, and depletion of BubR1
abolished the mitotic accumulation caused by RSK2 depletion, confirming BubR1
dependent SAC activation. Along with the shortening of inter-kinetochore
distance, these data suggested that weakening of the tension across sister
kinetochores by RSK2 depletion led to the activation of SAC. To test this, we
analyzed the RSK2 effects on the stability of kinetochore-microtubule
interactions, and found that RSK2-depleted cells formed less kinetochore
microtubule fibers. Moreover, RSK2 depletion resulted in the decrease of basal
level of microtubule as well as an irregular distribution of mitotic spindles,
which might lead to observed several mitotic progression defects such as increase
in unaligned chromosomes, defects in chromosome congression and a decrease in
pole-to-pole distance in these cells. Taken together, our data reveal that RSK2
affects mitotic progression by regulating the distribution, basal level and the
stability of mitotic spindles.
PMID- 27491411
TI - Targeted exome sequencing resolves allelic and the genetic heterogeneity in the
genetic diagnosis of nephronophthisis-related ciliopathy.
AB - Nephronophthisis-related ciliopathy (NPHP-RC) is a common genetic cause of end
stage renal failure during childhood and adolescence and exhibits an autosomal
recessive pattern of inheritance. Genetic diagnosis is quite limited owing to
genetic heterogeneity in NPHP-RC. We designed a novel approach involving the step
wise screening of Sanger sequencing and targeted exome sequencing for the genetic
diagnosis of 55 patients with NPHP-RC. First, five NPHP-RC genes were analyzed by
Sanger sequencing in phenotypically classified patients. Known pathogenic
mutations were identified in 12 patients (21.8%); homozygous deletions of NPHP1
in 4 juvenile nephronophthisis patients, IQCB1/NPHP5 mutations in 3 Senior-Loken
syndrome patients, a CEP290/NPHP6 mutation in 1 Joubert syndrome patient, and
TMEM67/MKS3 mutations in 4 Joubert syndrome patients with liver involvement. In
the remaining undiagnosed patients, we applied targeted exome sequencing of 34
ciliopathy-related genes to detect known pathogenic mutations in 7 (16.3%) of 43
patients. Another 18 likely damaging heterozygous variants were identified in 13
NPHP-RC genes in 18 patients. In this study, we report a variety of pathogenic
and candidate mutations identified in 55 patients with NPHP-RC in Korea using a
step-wise application of two genetic tests. These results support the clinical
utility of targeted exome sequencing to resolve the issue of allelic and genetic
heterogeneity in NPHP-RC.
PMID- 27491412
TI - Cardiovascular autonomic alterations in hospitalized patients with community
acquired pneumonia.
AB - BACKGROUND: Alterations of cardiac autonomic control (CAC) are associated with
poor outcomes in patients with infectious and non-infectious diseases. No
evaluation of CAC in patients with community-acquired pneumonia (CAP) has been
performed so far. The aim of the study was to assess CAC in patients with CAP and
evaluate the impact of its alterations on disease severity and clinical outcomes
in a multicenter, prospective, observational study. METHODS: Consecutive patients
hospitalized for CAP were enrolled between 2011 and 2013 two university hospitals
in Italy. CAC was assessed by linear spectral and non-linear symbolic analysis of
heart rate variability. The presence of severe CAP was evaluated on hospital
admission. The primary study outcome was time to clinical stability (TCS) during
hospitalization. RESULTS: Among the 75 patients enrolled (median age: 75 years;
57 % males), a significantly lower total variability and reduction of sympathetic
rhythmical component with predominant respiratory modulation was detected in
comparison to controls. Among CAP patients affected by a severe CAP on admission,
CAC showed a lower sympathetic modulation and predominant parasympathetic
oscillatory rhythm. At the multivariate analysis, variables independently
correlated with a TCS >7 days were total power, as marker of total variability,
[OR (95 % CI): 0.997 (0.994-1.000), p = 0.0454] and sympathetic modulation [OR
(95 % CI): 0.964 (0.932-0.998), p = 0.0367]. CONCLUSIONS: Loss of sympathetic
rhythmical oscillation is associated with a more severe disease and worse early
clinical outcome in hospitalized patients with CAP.
PMID- 27491413
TI - Multi-parametric surface plasmon resonance platform for studying liposome-serum
interactions and protein corona formation.
AB - When nanocarriers are administered into the blood circulation, a complex
biomolecular layer known as the "protein corona" associates with their surface.
Although the drivers of corona formation are not known, it is widely accepted
that this layer mediates biological interactions of the nanocarrier with its
surroundings. Label-free optical methods can be used to study protein corona
formation without interfering with its dynamics. We demonstrate the proof-of
concept for a multi-parametric surface plasmon resonance (MP-SPR) technique in
monitoring the formation of a protein corona on surface-immobilized liposomes
subjected to flowing 100 % human serum. We observed the formation of formulation
dependent "hard" and "soft" coronas with distinct refractive indices, layer
thicknesses, and surface mass densities. MP-SPR was also employed to determine
the affinity (K D ) of a complement system molecule (C3b) with cationic liposomes
with and without polyethylene glycol. Tendency to create a thick corona
correlated with a higher affinity of opsonin C3b for the surface. The label-free
platform provides a fast and robust preclinical tool for tuning nanocarrier
surface architecture and composition to control protein corona formation.
PMID- 27491414
TI - Lipopolysaccharide suppresses human immunodeficiency virus 1 reverse
transcription in macrophages.
AB - HIV-1-infected macrophages are long-lived and act as human immunodeficiency virus
1 (HIV-1) virus reservoirs. Lipopolysaccharide (LPS) has been demonstrated to
suppress HIV-1 replication in macrophages, but the mechanism is not clear.
Previous research suggested that downregulation of CD4 and CCR5 as well as
blockage of the interaction of HIV-1 with cells are major causes of inhibition of
HIV-1 replication in macrophages by LPS. In order to study whether LPS blocks the
post-entry event of HIV-1 replication, we developed a macrophage HIV-1 infection
model by using VSV-G pseudotyped HIV-1-luciferase virus to infect THP-1
differentiated macrophage-like cells. We found that LPS can suppress HIV-1
replication at post-entry steps. Further study suggested that HIV-1 reverse
transcription was blocked by LPS, but addition of exogenous deoxyribonucleosides
led to only partial recovery of HIV-1 replication. However, the inhibition of pro
inflammatory pathway completely rescued HIV-1 replication. Thus, our study shows
that LPS can suppress the events of HIV-1 replication post-entry, including
reverse transcription, and this restriction is mediated by more than one
mechanism.
PMID- 27491415
TI - Morphological and physiological differences between dehiscent and indehiscent
anthers of Chrysanthemum morifolium.
AB - Spray cut chrysanthemums ornamental value and vase life are rapidly reduced with
an increase in the pollen dispersal of the middle tubular bisexual flowers, and
excessive pollen grains floating in the air are usually harmful to people. Thus,
two cultivars were selected: the dehiscent 'Qx-097' and the indehiscent 'Qx-007',
to investigate the morphological, structural and physiological differences in
anthers. (1) Prior to the opening of the tubular flower, the anther was
completely dehisced, and the pollen grains of 'Qx-097' were then released. 'Qx
007' inflorescences showed no pollen dispersal, and this cultivar was therefore
not contaminated by its own pollen grains during flowering. (2) The anther cell
structure of 'Qx-007' was abnormal, such that the entire anther wall exhibited
hypertrophy due to the non-selective thickening of the endothecium cell size in
different areas. Moreover, cracks did not form in the 'Qx-007' anther due to
failure of septum degradation and stomium breakage, which resulted in the anther
locules being inwardly crushed. Besides, the indehiscent anther accompanies
partial pollen abortion due to the impairment of tapetum development, this is not
conducive to pollen dispersal. (3) The 'Qx-007' anther contained higher water
levels compared with 'Qx-097', and the dehydration of the 'Qx-007' anther was
relatively moderate. Furthermore, the 'Qx-007' anther exhibited higher Ca2+ and
Mg2+ levels compared with 'Qx-097' during dehiscing periods. (4) The 'Qx-007'
anther showed significantly lower jasmonic acid levels and higher indole-3-acetic
acid levels compare with the 'Qx-097' anther. These results suggest that the
endothecium, septum and stomium constituent of the anther structure exhibit
developmental abnormalities, which likely serve as the cellular basis of anther
indehiscence. In addition, anther dehydration, the enhancement of anther cell
toughness due to a high level of ions, and JA (IAA) dysregulation may be the
determining physiological factors of anther indehiscence.
PMID- 27491416
TI - Cross-Cultural Perspectives on Parent-Adolescent Discrepancies: Existing Findings
and Future Directions.
AB - As summarized in this commentary, the first generation of cross-informant
agreement research focused on perceptions of child and adolescent mental health.
Contributions of this research include demonstrating that modest cross-informant
agreement is a very robust phenomenon, utilizing numerous statistical approaches
to measure degree of agreement, and identifying many factors that moderate
agreement. An important focus of this work has been using multi-society
international comparisons to examine cross-cultural similarities and differences
in cross-informant agreement. The articles in this Special Issue represent a
significant paradigm shift in which cross-informant agreement is examined as an
independent variable predicting a wide variety of outcomes. Furthermore, moving
beyond perceptions of adolescent mental health, these articles compare parent and
adolescent perceptions of diverse aspects of family functioning (e.g., family
conflict, parent-adolescent communication, family relationships, parental
authority). Additionally, the research presented in this Special Issue employs
innovative and sophisticated statistical techniques. Although the Special Issue
represents some first steps toward considering cross-cultural aspects of
perceptions of family functioning, much work still needs to be done in this area.
Some suggestions for future research strategies to accomplish this goal conclude
this commentary.
PMID- 27491417
TI - Evaluation of environmental quality of two estuaries in Ilha do Maranhao, Brazil,
using histological and genotoxic biomarkers in Centropomus undecimalis (Pisces,
Centropomidae).
AB - Estuaries are subjected to continual environmental impacts from activities in the
catchment areas. This research assessed the quality of two estuarine habitats
located in Ilha do Maranhao, Brazil, through histological and genotoxic
biomarkers in Centropomus undecimalis, comparing the data obtained to metal,
physical, and chemical concentrations of water samples. The gill histological
alterations were analyzed by the histological alteration index and genotoxic
lesions in erythrocytes were detected by the Micronucleus Test. The analysis of
metals revealed that all water samples contained at least two elements with
concentrations higher than that allowed by the current Brazilian law. For gill
histological analysis, snook of both areas assessed exhibited moderate lesions,
indicating that the local fish are affected by environmental stress. Micronucleus
analysis of snook showed that the Bacanga river basin is the most affected. In
addition to assessing the health of commercial fish populations, the information
about the biomarkers used for the species can serve to contribute to the
preparation and/or application of health assessment models and implementation of
environmental recovery policies for coastal aquatic environments.
PMID- 27491418
TI - Valorisation of tuna processing waste biomass for recovery of functional and
antioxidant peptides using enzymatic hydrolysis and membrane fractionation
process.
AB - The enzymatic hydrolysis using Prolyve BS coupled to membrane process
(Ultrafiltration (UF) and nanofiltration (NF)) is a means of biotransformation of
tuna protein waste to Tuna protein hydrolysate (TPH) with higher added values.
This method could be an effective solution for the production of bioactive
compounds used in various biotechnological applications and minimizing the
pollution problems generated by the seafood processing industries. The amino acid
composition, functional and antioxidant properties of produced TPH were
evaluated. The results show that the glutamic acid, aspartic acid, glycine,
alaline, valine and leucine were the major amino acids detected in the TPH
profile. After membrane fractionation process, those major amino acids were
concentrated in the NF retentate (NFR). The NFR and NF permeate (NFP) have a
higher protein solubility (>95 %) when compared to TPH (80 %). Higher oil and
water binding capacity were observed in TPH and higher emulsifying and foam
stability was found in UF retentate. The NFP showed the highest DPPH radical
scavenging activity (65 %). The NFR contained antioxidant amino acid (30.3 %)
showed the highest superoxide radical and reducing power activities. The TPH
showed the highest iron chelating activity (75 %) compared to other peptide
fractions. The effect of the membrane fractionation on the molecular weight
distribution of the peptide and their bioactivities was underlined. We concluded
that the TPH is a valuable source of bioactive peptides and their peptide
fractions may serve as useful ingredients for application in food industry and
formulation of nutritional products.
PMID- 27491419
TI - Potential ecological and human health risks of heavy metals in surface soils
associated with iron ore mining in Pahang, Malaysia.
AB - The composition of heavy metals (and metalloid) in surface soils of iron ore mine
impacted areas has been evaluated of their potential ecological and human health
risks. The mining areas included seven selected locations in the vicinity of
active and abandoned iron ore-mining sites in Pahang, Malaysia. Heavy metals such
as Fe, Mn, Cu, Zn, Co, Pb, Cr, Ni, and Cd and metalloid As were present in the
mining soils of the studied area, while Cu was found exceeding the soil guideline
value at all sampling locations. However, the assessment of the potential
ecological risk index (RI) indicated low ecological risk (RI between 44 and 128)
with respect to Cd, Pb, Cu, As, Zn, Co, and Ni in the surface soils.
Contributions of potential ecological risk [Formula: see text]by metal elements
to the total potential ecological RI were evident for Cd, As, Pb, and Cu.
Contribution of Cu appears to be consistently greater in the abandoned mining
area compared to active iron ore-mining site. For non-carcinogenic risk, no
significant potential health risk was found to both children and adults as the
hazard indices (HIs) were all below than 1. The lifetime cancer risk (LCR)
indicated that As has greater potential carcinogenic risk compared to other
metals that may induce carcinogenic effects such as Pb, Cr, and Cd, while the LCR
of As for children fell within tolerable range for regulatory purposes.
Irrespective of carcinogenic or non-carcinogenic risk, greater potential health
risk was found among children (by an order of magnitude higher for most metals)
compared to adults. The hazard quotient (HQ) and cancer risk indicated that the
pathways for the risk to occur were found to be in the order of ingestion >
dermal > inhalation. Overall, findings showed that some metals and metalloid were
still present at comparable concentrations even long after cessation of the iron
ore-mining activities.
PMID- 27491420
TI - Assessment of polybrominated diphenyl ethers in sediment of Asunle stream of the
Obafemi Awolowo University, Ile-Ife, Nigeria.
AB - Assessment of levels of polybrominated diphenyl ethers (PBDEs) from the sediment
of Asunle stream, an adjourning stream of the Obafemi Awolowo University
dumpsite, has been carried out. Sediment samples were collected from the stream
at six locations for a period of 8 months, composed of 4 months each of wet (May
Aug) and dry (Nov-Feb) seasons. Soxhlet extraction was employed for the isolation
of all the target compounds from the sediment samples. Extracts were further
subjected to multi-layer column chromatography employing different forms of
silica gel. The prepared samples were analyzed using GC-MS. The overall mean
concentrations of the total PBDEs ranged from 1.80 to 9.46 ng/g. The results
showed that the concentrations of the PBDEs were slightly higher during the wet
season than those during the dry season. In all the studied locations, BDE28,
BDE47, BDE99, BDE100, BDE153, and BDE154 were detected in all the sediment
samples at concentrations that ranged from 0.73 to 10.43 ng/g. Results of this
study indicated that BDE153 was the major pollutant of the Asunle stream
sediments.
PMID- 27491421
TI - Physiological and biochemical mechanisms of spermine-induced cadmium stress
tolerance in mung bean (Vigna radiata L.) seedlings.
AB - The role of exogenous spermine (0.25 mM Spm, a type of polyamine (PA) in reducing
Cd uptake and alleviating Cd toxicity (containing 1 and 1.5 mM CdCl2 in the
growing media) effects was studied in the mung bean (Vigna radiata L. cv. BARI
Mung-2) plant. Exogenously applied Spm reduced Cd content, accumulation, and
translocation in different plant parts. Increasing phytochelatin content,
exogenous Spm reduced Cd accumulation and translocation. Spm application reduced
the Cd-induced oxidative damage which was reflected from the reduction of H2O2
content, O2*- generation rate, lipoxygenase (LOX) activity, and lipid
peroxidation level and also reflected from the reduction of spots of H2O2 and O2*
from mung bean leaves (compared to control treatment). Spm pretreatment
increased non-enzymatic antioxidant contents (ascorbate, AsA, and glutathione,
GSH) and activities of antioxidant enzymes such as superoxide dismutase (SOD),
catalase (CAT), glutathione S-transferase (GST), monodehydroascorbate reductase
(MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) which
reduced oxidative stress. The cytotoxicity of methylglyoxal (MG) is also reduced
by exogenous Spm because it enhanced glyoxalase system enzymes and components.
Through osmoregulation, Spm maintained a better water status of Cd-affected mung
bean seedlings. Spm prevented the chl damage and increased its content. Exogenous
Spm also modulated the endogenous free PAs level which might have the roles in
improving physiological processes including antioxidant capacity, osmoregulation,
and Cd and MG detoxification capacity. The overall Spm-induced tolerance of mung
bean seedlings to Cd toxicity was reflected through improved growth of mung bean
seedlings.
PMID- 27491422
TI - Combination of biochar amendment and phytoremediation for hydrocarbon removal in
petroleum-contaminated soil.
AB - Remediation of soils contaminated with petroleum is a challenging task. Four
different bioremediation strategies, including natural attenuation, biochar
amendment, phytoremediation with ryegrass, and a combination of biochar and
ryegrass, were investigated with greenhouse pot experiments over a 90-day period.
The results showed that planting ryegrass in soil can significantly improve the
removal rate of total petroleum hydrocarbons (TPHs) and the number of
microorganisms. Within TPHs, the removal rate of total n-alkanes (45.83 %) was
higher than that of polycyclic aromatic hydrocarbons (30.34 %). The amendment of
biochar did not result in significant improvement of TPH removal. In contrast, it
showed a clear negative impact on the growth of ryegrass and the removal of TPHs
by ryegrass. The removal rate of TPHs was significantly lower after the amendment
of biochar. The results indicated that planting ryegrass is an effective
remediation strategy, while the amendment of biochar may not be suitable for the
phytoremediation of soil contaminated with petroleum hydrocarbons.
PMID- 27491423
TI - Use of the Modified Checklist for Autism, Revised with Follow Up-Albanian to
Screen for ASD in Albania.
AB - The Modified Checklist for Autism in Toddlers Revised-Albanian screener (M-CHAT-R
A) was used to screen 2594 toddlers, aged 16-30 months, at well-child visits. Two
hundred fifty-three (9.75 %) screened positive; follow up on failed items were
conducted by phone with 127 (50 %); the remainder were lost to follow-up. Twenty
six toddlers (21 %) continued to screen positive; 19 received full evaluations,
which assessed for ASD with the Autism Diagnostic Observation Schedule and
developmental delays with the Parents Assessment of Developmental Status
Developmental Milestones. All evaluated children had significant delays; 17 of
the 19 met criteria for Autism/ASD. Removal of three items improved performance.
Although Albania and the US are quite different in culture and language, key
features of ASD appeared very similar.
PMID- 27491425
TI - ?
PMID- 27491424
TI - Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders.
AB - Patients with autism spectrum disorder (ASD) are at increased risk for fracture,
and peri-pubertal boys with ASD have lower bone mineral density (BMD) than
controls. Data are lacking regarding BMD in older adolescents with ASD. We
compared BMD using dual-energy X-ray absorptiometry in 9 adolescents/young adults
with ASD against 9 typically developing matched controls. Patients with ASD and
controls were excluded if they had other underlying conditions that may affect
bone. Compared to controls, patients with ASD had (i) lower femoral neck and hip
BMD Z-scores, and (ii) lower spine, femoral neck and hip height adjusted BMD Z
scores even after controlling for BMI. Understanding the underlying
pathophysiology will be key to developing therapies to improve BMD and reduce
fracture risk.
PMID- 27491426
TI - Systematic review of ixabepilone for treating metastatic breast cancer.
AB - BACKGROUND: Ixabepilone is now a Food and Drug Administration-approved
therapeutic option for patients with metastatic breast cancer (MBC) whose disease
has progressed despite prior anthracycline and taxane therapy. We conducted a
systematic review and meta-analysis to systematically evaluate the efficacy and
safety of ixabepilone for treating metastatic breast cancer. METHODS: A
systematic review and meta-analysis were conducted. Randomized controlled studies
applying ixabepilone for treating MBC were included. The primary outcome was
Overall Survival (OS). The authors of primary articles were contacted and
methodological quality was evaluated. Subgroups were drawn based on intervention
measures; heterogeneity and bias were discussed. RESULTS: Eight studies with 5247
patients were included. Compared with a weekly schedule, a triweekly schedule of
ixabepilone was better at improving overall response rate (ORR), while there were
no differences in improving OS and progression-free survival (PFS). Ixabepilone
plus capecitabine was superior to capecitabine monotherapy in improving OS, PFS
and ORR. Paclitaxel was more effective than ixabepilone in terms of OS and PFS.
There was no difference in the improvement of ORR, clinical benefit rate (CBR)
and disease control rate (DCR) between ixabepilone and eribulin. CONCLUSIONS:
Current evidence suggests that a triweekly schedule of ixabepilone is more
effective than weekly dosing in improving ORR. Use of ixabepilone in combination
with capecitabine possesses superior clinical efficacy to the use of capecitabine
alone. Paclitaxel was more effective than ixabepilone in terms of OS and PFS. The
efficacy and safety between ixabepilone and eribulin were identical.
PMID- 27491427
TI - Implementation of a post-arrest care team: understanding the nuances of a team
based intervention.
AB - BACKGROUND: Despite advances in the management of sudden cardiac arrest,
mortality for patients admitted to hospital is still greater than 50 %. Lack of
familiarity and experience with post-cardiac arrest patients and lack of
interdisciplinary collaboration between emergency and ICU staff have been
highlighted as potential barriers to optimal care. To address these barriers, a
specialized Post Arrest Consult Team (PACT) was implemented at two urban academic
centers. Our objective was to describe the PACT implementation from the
participant perspective in order to explore potentially mitigating factors on
effectiveness of the intervention and inform other institutions who may be
considering a similar approach. METHODS: Using an ethnographic style approach, we
collected data throughout the implementation period using both key informant
interviews and non-participant observation. The data were analyzed using
interpretive descriptive analysis techniques. RESULTS: The PACT intervention was
taken up differently in each of the two participating institutions. Participants
spoke about the difficulty in maintaining a dynamic interaction between the team
members and a shared sense of purpose, the challenge of off-service consulting
and the impact of the lack of data feedback to support whether the project was
effecting change. CONCLUSIONS: It appears that purposefully creating a "sense of
team," the team composition and organizational culture and provision of
performance feedback are important facilitators to ensuring uptake of a team
based intervention like the PACT model. Reporting of the intervention design and
actual implementation experience like we have done here is crucial to allow
readers to judge the quality of the study, to properly replicate it, and to
contemplate how various factors may influence the outcome of a complex
intervention.
PMID- 27491430
TI - Quasisolitons in self-diffusive excitable systems, or Why asymmetric diffusivity
obeys the Second Law.
AB - Solitons, defined as nonlinear waves which can reflect from boundaries or
transmit through each other, are found in conservative, fully integrable systems.
Similar phenomena, dubbed quasi-solitons, have been observed also in dissipative,
"excitable" systems, either at finely tuned parameters (near a bifurcation) or in
systems with cross-diffusion. Here we demonstrate that quasi-solitons can be
robustly observed in excitable systems with excitable kinetics and with self
diffusion only. This includes quasi-solitons of fixed shape (like KdV solitons)
or envelope quasi-solitons (like NLS solitons). This can happen in systems with
more than two components, and can be explained by effective cross-diffusion,
which emerges via adiabatic elimination of a fast but diffusing component. We
describe here a reduction procedure can be used for the search of complicated
wave regimes in multi-component, stiff systems by studying simplified, soft
systems.
PMID- 27491429
TI - Radiation exposure of the spleen during (177)Lu-DOTATATE treatment and its
correlation with haematological toxicity and spleen volume.
AB - BACKGROUND: Somatostatin analogue-based radionuclide therapy with (177)Lu
DOTATATE is an important treatment option for patients with advanced
neuroendocrine tumours overexpressing somatostatin receptors. In addition to the
kidneys, the bone marrow is a major dose-limiting organ. The correlation between
developed haematological toxicity and absorbed dose to the bone marrow is poor,
which indicates that other factors affect haematological response. The spleen has
an important role in the haematopoetic system, including being a reservoir for
blood cells. It is also the organ that receives the highest mean absorbed dose
during (177)Lu-DOTATATE treatment. The aim of this study was to analyse mean
absorbed dose to the spleen and its correlation with haematological toxicity, and
to explore changes in splenic volume. The study included 41 patients treated with
7.2 GBq (3.5-8.3 GBq) of (177)Lu-DOTATATE on two to five occasions. Following
each fraction, planar whole-body scans were acquired at 2, 24, 48, and 168 h, and
a SPECT/CT at 24 h post-injection. Mean absorbed spleen dose was calculated
utilising planar images for time-activity data and SPECT to adjust activity
amounts. Splenic volume information was collected from diagnostic CT scans at
baseline and follow-up. RESULTS: Median and total absorbed spleen doses were
estimated to 4.5 and 15 Gy, respectively. Total absorbed spleen dose correlated
with decrease in Hb (p = 0.02), but not WBC (p = 0.31) or PLT (p = 0.65) counts.
For patients without bone metastases, mean absorbed spleen dose correlated with
decrease in PLT (p = 0.04) but not Hb (p = 0.16) or WBC (p = 0.42) counts. The
spleen volume was reduced to 75 % (p < 0.001) of original values (200 vs. 260 ml)
at a mean follow-up of 36 months. CONCLUSIONS: Haematological toxicity according
to Hb counts was moderately but significantly correlated with total absorbed
spleen dose. This supports the possibility that radiation exposure of the spleen
affects overall haematological response during (177)Lu-DOTATATE treatment.
PMID- 27491431
TI - Power and glory: applying participatory action research in public health.
PMID- 27491432
TI - Time trends in health inequalities due to care in the context of the Spanish
Dependency Law.
AB - OBJECTIVE: In Spain, responsibility for care of old people and those in
situations of dependency is assumed by families, and has an unequal social
distribution according to gender and socioeconomic level. This responsibility has
negative health effects on the carer. In 2006, the Dependency Law recognised the
obligation of the State to provide support. This study analyses time trends in
health inequalities attributable to caregiving under this new law. METHODS: Study
of trends using two cross-sectional samples from the 2006 and 2012 editions of
the Spanish National Health Survey (27,922 and 19,995 people, respectively). We
compared fair/poor self-rated health, poor mental health (GHQ-12 >2), back pain,
and the use of psychotropic drugs between non-carers, carers sharing care with
other persons, and those providing care alone. We obtain prevalence ratios by
fitting robust Poisson regression models. RESULTS: We observed no change in the
social profile of carers according to gender or social class. Among women, the
difference in all health indicators between carers and non-carers tended to
decrease among those sharing care but not among lone carers. Inequalities tend to
decrease slightly in both groups of men carers. CONCLUSIONS: Between 2006 and
2012, trends in health inequalities attributable to informal care show different
trends according to gender and share of responsibility. It is necessary to
redesign and implement policies to reduce inequalities that take into account the
most affected groups, such as women lone carers. Policies that strengthen the
fair social distribution of care should also be adopted.
PMID- 27491433
TI - Advances and Challenges in Genomic Selection for Disease Resistance.
AB - Breeding for disease resistance is a central focus of plant breeding programs, as
any successful variety must have the complete package of high yield, disease
resistance, agronomic performance, and end-use quality. With the need to
accelerate the development of improved varieties, genomics-assisted breeding is
becoming an important tool in breeding programs. With marker-assisted selection,
there has been success in breeding for disease resistance; however, much of this
work and research has focused on identifying, mapping, and selecting for major
resistance genes that tend to be highly effective but vulnerable to breakdown
with rapid changes in pathogen races. In contrast, breeding for minor-gene
quantitative resistance tends to produce more durable varieties but is a more
challenging breeding objective. As the genetic architecture of resistance shifts
from single major R genes to a diffused architecture of many minor genes, the
best approach for molecular breeding will shift from marker-assisted selection to
genomic selection. Genomics-assisted breeding for quantitative resistance will
therefore necessitate whole-genome prediction models and selection methodology as
implemented for classical complex traits such as yield. Here, we examine multiple
case studies testing whole-genome prediction models and genomic selection for
disease resistance. In general, whole-genome models for disease resistance can
produce prediction accuracy suitable for application in breeding. These models
also largely outperform multiple linear regression as would be applied in marker
assisted selection. With the implementation of genomic selection for yield and
other agronomic traits, whole-genome marker profiles will be available for the
entire set of breeding lines, enabling genomic selection for disease at no
additional direct cost. In this context, the scope of implementing genomics
selection for disease resistance, and specifically for quantitative resistance
and quarantined pathogens, becomes a tractable and powerful approach in breeding
programs.
PMID- 27491428
TI - Molecular mechanisms involved in dendritic cell dysfunction in cancer.
AB - Dendritic cells (DC) play a pivotal role in the tumor microenvironment (TME). As
the primary antigen-presenting cells in the tumor, DCs modulate anti-tumor
responses by regulating the magnitude and duration of infiltrating cytotoxic T
lymphocyte responses. Unfortunately, due to the immunosuppressive nature of the
TME, as well as the inherent plasticity of DCs, tumor DCs are often
dysfunctional, a phenomenon that contributes to immune evasion. Recent progresses
in our understanding of tumor DC biology have revealed potential molecular
targets that allow us to improve tumor DC immunogenicity and cancer
immunotherapy. Here, we review the molecular mechanisms that drive tumor DC
dysfunction. We discuss recent advances in our understanding of tumor DC
ontogeny, tumor DC subset heterogeneity, and factors in the tumor
microenvironment that affect DC recruitment, differentiation, and function.
Finally, we describe potential strategies to optimize tumor DC function in the
context of cancer therapy.
PMID- 27491434
TI - Quarantine Regulations and the Impact of Modern Detection Methods.
AB - Producers worldwide need access to the best plant varieties and cultivars
available to be competitive in global markets. This often means moving plants
across international borders as soon as they are available. At the same time,
quarantine agencies are tasked with minimizing the risk of introducing exotic
pests and pathogens along with imported plant material, with the goal to protect
domestic agriculture and native fauna and flora. These two drivers, the movement
of more plant material and reduced risk of pathogen introduction, are at odds.
Improvements in large-scale or next-generation sequencing (NGS) and
bioinformatics for data analysis have resulted in improved speed and accuracy of
pathogen detection that could facilitate plant trade with reduced risk of
pathogen movement. There are concerns to be addressed before NGS can replace
existing tools used for pathogen detection in plant quarantine and certification
programs. Here, we discuss the advantages and possible pitfalls of this
technology for meeting the needs of plant quarantine and certification.
PMID- 27491435
TI - Fungal and Oomycete Diseases of Tropical Tree Fruit Crops.
AB - The tropics produce a range of fruit from tree crops that cannot be grown in
colder climates. Bananas, mangos, several nuts, spices, coffee, and cacao are
widely traded and much sought after around the world. However, the sustainable
production of these tropical tree fruit crops faces significant challenges. Among
these, losses due to pests and diseases play a large part in reducing yields,
quality, and profitability. Using bananas and cacao as key examples, we outline
some of the reasons fungal and oomycete diseases cause such significant losses to
tropical tree crops. Cultivation of monocultures derived from limited genetic
diversity, environmental conditions conducive for disease development, high
levels of disease incidence and severity, a lack of disease resistance in
planting materials, shortages of labor, and inadequate infrastructure and
investment pose significant challenges, especially for smallholder producers. The
expansion of travel and trade has given rise to emerging infectious plant
diseases that add further insecurity and pressure. We conclude that holistic
actions are needed on multiple fronts to address the growing problem of disease
in tropical fruit tree crops.
PMID- 27491436
TI - DNA Methylation and Demethylation in Plant Immunity.
AB - Detection of plant and animal pathogens triggers a massive transcriptional
reprogramming, which is directed by chromatin-based processes, and ultimately
results in antimicrobial immunity. Although the implication of histone
modifications in orchestrating biotic stress-induced transcriptional
reprogramming has been well characterized, very little was known, until recently,
about the role of DNA methylation and demethylation in this process. In this
review, we summarize recent findings on the dynamics and biological relevance of
DNA methylation and demethylation in plant immunity against nonviral pathogens.
In particular, we report the implications of these epigenetic regulatory
processes in the transcriptional and co-transcriptional control of immune
responsive genes and discuss their relevance in fine-tuning antimicrobial immune
responses. Finally, we discuss the possible yet elusive role of DNA methylation
and demethylation in systemic immune responses, transgenerational immune priming,
and de novo epiallelism, which could be adaptive.
PMID- 27491437
TI - Criteria for recommendation and expert consensus papers: from the European
Association of Cardiovascular Imaging Scientific Documents Committee.
AB - The recommendations given in this document are intended as a guide for the
writing committees with the aim to harmonize the style and content of EACVI
expert consensus and recommendation documents.
PMID- 27491438
TI - Small aortic root in aortic valve stenosis: clinical characteristics and
prognostic implications.
AB - Aims: In aortic valve stenosis (AS), having a small aortic root may influence
both the assessment of AS severity and the treatment strategy. The aim was to
test the prognostic implications of having a small aortic root in AS within a
large prospective study. Methods and results: We used data from 4.3-year follow
up of 1560 patients with asymptomatic, initially mostly moderate AS enrolled in
the Simvastatin and Ezetimibe in Aortic Stenosis study. A small aortic root was
defined as inner aortic sinotubular junction diameter indexed for body height
<1.4 cm/m in women and <1.5 cm/m in men. A small aortic root was found in 270
patients (17.3%) at baseline. Having a small aortic root was associated with
larger aortic root wall thickness, higher pressure recovery, lower systemic
arterial compliance, left ventricular mass index, and female sex in a
multivariable logistic regression analysis (all P < 0.05). In the Cox regression
analysis, having a small aortic root at baseline was associated with higher
hazard rates of ischaemic cardiovascular events (n = 268; HR 1.55, 95% CI 1.16
2.06), non-haemorrhagic stroke (n = 55; HR 1.88, 95% CI 1.04-3.41), and
cardiovascular death (n = 81; HR 2.08, 95% CI 1.28-3.39) (all P < 0.05) after
adjusting for confounders, including randomized study treatment, sex,
hypertension, AS severity, and aortic valve replacement. Conclusion: In AS
patients without known cardiovascular disease or diabetes, having a small aortic
root was associated with increased ischaemic cardiovascular events and mortality.
The results suggest a relation between the presence of a small aortic root and
that of subclinical atherosclerosis. Clinical trial registration:
ClinicalTrials.gov identifier: NCT00092677.
PMID- 27491439
TI - Multi-subtype influenza virus-like particles incorporated with flagellin and
granulocyte-macrophage colony-stimulating factor for vaccine design.
AB - Virus-like particle (VLP) technology is an attractive platform for seasonal and
pandemic influenza vaccine development. We previously showed that influenza VLPs
can be modified using M2 fusion with molecular adjuvants such as Salmonella
typhimurium flagellin (FliC) to enhance VLP immunogenicity. For this study, three
types of chimeric VLPs were incorporated with FliC, granulocyte-macrophage colony
stimulating factor (GM-CSF), or both GM-CSF and FliC (GM-CSF/FliC) to enhance
anti-influenza immunogenicity. Our results indicate that immunizations with the
chimeric FliC VLPs and GM-CSF/FliC H5N1 VLPs elicited more potent and broadly
neutralizing antibodies and neuraminidase-inhibiting antibodies in sera, and
induced higher numbers of hemagglutinin-specific antibody-secreting cells and
germinal center B cell subsets in splenoctyes. Immunization with the chimeric GM
CSF H5N1 VLPs induced stronger Th1 and Th2 cellular responses. The chimeric GM
CSF/FliC H5N1 VLP constructs were further obtained to include H7 or H1H7 bi- or
tri-subtype. It is our hope that these findings provide useful information for
developing multi-subtype influenza vaccines.
PMID- 27491440
TI - Functional evaluation of Heat Shock Proteins 70 (HSP70/HSC70) on Rhodnius
prolixus (Hemiptera, Reduviidae) physiological responses associated with feeding
and starvation.
AB - Blood-sucking vectors must overcome thermal stress caused by intake of
proportionally large amounts of warm blood from their hosts. In response to this,
Heat Shock Proteins (HSPs) such as the widely studied HSP70 family (the inducible
HSP70 and the cognate form HSC70, known for their role in preserving essential
cellular functions) are rapidly up-regulated in their tissues. The triatomine
Rhodnius prolixus is an important vector of Trypanosoma cruzi, the causative
pathogen of Chagas' disease, and is also a model organism for studying insect
biology and physiology. In this work, we observed that the expression of Rhodnius
prolixus HSP70 was rapidly up-regulated in response to thermal shocks (0 degrees
C and 40 degrees C) and also during the first hours after feeding on blood.
HSP70/HSC70 RNAi knockdown elicited important alterations in R. prolixus
physiological responses triggered by blood meal and starvation. HSP70/HSC70
knockdown insects showed lower resistance to prolonged starvation in comparison
to appropriate controls, dying between 32 and 40 days after dsRNA injection.
After blood feeding, the physiological effects of HSP70/HSC70 knockdown were more
prominent and the insects died even earlier, within 14-20 days after feeding (21
27 days after dsRNA injection). These bugs showed impaired blood processing and
digestion, reduced energetic metabolism and the midgut immune responses were
compromised. Our findings suggest that HSP70/HSC70 depletion affected R. prolixus
in starvation or fed conditions. After feeding, the arrival of blood in the
digestive tract of knockdown insects fails to activate essential signaling
pathways involved in blood processing, producing several alterations in their
physiological processes enough to generate a premature death.
PMID- 27491441
TI - Molecular and functional characterization of Bemisia tabaci aquaporins reveals
the water channel diversity of hemipteran insects.
AB - The Middle East-Asia Minor 1 (MEAM1) whitefly, Bemisia tabaci (Gennadius) is an
economically important pest of food, fiber, and ornamental crops. This pest has
evolved a number of adaptations to overcome physiological challenges, including
1) the ability to regulate osmotic stress between gut lumen and hemolymph after
imbibing large quantities of a low nitrogen, sugar-rich liquid diet; 2) the
ability to avoid or prevent dehydration and desiccation, particularly during egg
hatching and molting; and 3) to be adapted for survival at elevated temperatures.
One superfamily of proteins involved in the maintenance of fluid homeostasis in
many organisms includes the aquaporins, which are integral membrane channel
proteins that aid in the rapid flux of water and other small solutes across
biological membranes. Here, we show that B. tabaci has eight aquaporins (BtAqps),
of which seven belong to the classical aquaporin 4-related grade of channels,
including Bib, Drip, Prip, and Eglps and one that belongs to the unorthodox grade
of aquaporin 12-like channels. B. tabaci has further expanded its repertoire of
water channels through the expression of three BtDrip2 amino-terminal splice
variants, while other hemipteran species express amino- or carboxyl-terminal
isoforms of Drip, Prip, and Eglps. Each BtAqp has unique transcript expression
profiles, cellular localization, and/or substrate preference. Our phylogenetic
and functional data reveal that hemipteran insects lost the classical glp genes,
but have compensated for this by duplicating the eglp genes early in their
evolution to comprise at least three separate clades of glycerol transporters.
PMID- 27491442
TI - Two-trocar appendectomy in children - description of technique and comparison
with conventional laparoscopic appendectomy.
AB - BACKGROUND: The aim of the study was to describe the technique of two-trocar
laparoscopic appendectomy and compare the outcome between two- and three-trocar
techniques in children. METHODS: All children who underwent laparoscopic surgery
for suspected appendicitis from 2006 to 2014 in a center for pediatric surgery
were included in the study. Converted surgeries and patients with appendiceal
abscess or concomitant intestinal obstruction were excluded. A total of 259
children underwent appendectomy with either two (35 %) or three (65 %)
laparoscopic trocars according to the surgeons' preference and intraoperative
judgment. Patient demographics, clinical symptoms, surgery characteristics, and
complications were reviewed. RESULTS: The mean age of the children was 10.4 years
(range, 1-14 years). The mean follow-up time was 41.2 months (SD +/- 29.2). No
significant differences in age, gender, weight, or signs and symptoms were found
between the two- and three-trocar groups. The mean surgery time was significantly
shorter in the two-trocar group (47 min) than in the three-trocar group (66 min;
p < 0.001). The rates of surgical complications were 2 % vs. 4 %, (p = 0.501),
and the rates of postoperative complications were 0 % vs. 5 % (p = 0.054), in the
two- and three-trocar groups. The overall incidence of postoperative wound
infection was low (<1 %) and did not differ between groups. CONCLUSIONS: Two
trocar laparoscopic appendectomy seems to be a safe and feasible technique with a
low rate of postoperative wound infections. The present findings demonstrate that
when the two-trocar technique could be applied, it is a good complement to the
conventional three-trocar technique.
PMID- 27491443
TI - Who Is Not a Candidate for a 1-Day Hospital-Based Total Knee Arthroplasty?
AB - BACKGROUND: Short-stay total knee arthroplasty (TKA), defined as a 1-day length
of stay (LOS), is feasible in many patients, yet variables identifying who are
candidates for a short stay are not well described in literature. With an
emphasis on cost-efficiency, we examined preoperative patient characteristics and
perioperative hospital factors that correlated with a longer LOS. METHODS: A
retrospective review of 381 primary TKAs was performed. Clinical measures
differentiating a 1-day LOS group from that of a >=2-day LOS group were
identified. RESULTS: Multiple logistic regression demonstrated older age (odds
ratio [OR], 1.92; 95% confidence interval [CI], 1.34-2.77; P < .001), female
gender (OR, 4.22; 95% CI, 2.35-7.57; P < .001), American Society of
Anesthesiologists score 3 or 4 (OR, 2.00; 95% CI, 1.01-3.95; P = .046), atrial
fibrillation (OR, 8.87; 95% CI, 1.81-43.47; P = .007), and prior TKA on the
contralateral side (OR, 3.57; 95% CI, 1.27-10.05; P = .016) as significant
preoperative characteristics correlating with the >=2-day LOS group. The most
significant hospital perioperative factor associated with longer stays was
patients not ambulating on the day of surgery (OR, 4.09; 95% CI, 1.77-9.48; P =
.001). Walking 150 ft (93% sensitive, 35% specific) on the day of surgery was
predictive of patients in the 1-day LOS group. Hospital costs were US$1873 (P <
.001) lower for patients in the 1-day group. CONCLUSION: Shorter stays decrease
costs associated with TKA, and more refined predictive models are needed to
optimize discharge protocols. Preoperative data help allocate limited healthcare
resources toward patients more likely to leave in 1 day, while perioperative data
facilitate learning to create a more efficient hospital process.
PMID- 27491444
TI - Letter to the Editor on "Balancing Thromboprophylaxis and Bleeding in Total Joint
Arthroplasty: Impact of Eliminating Enoxaparin and Predonation and Implementing
Pneumatic Compression and Tranexamic Acid".
PMID- 27491445
TI - Response to Letter to the Editor on "Large Metal Heads and Vitamin E Polyethylene
Increase Frictional Torque in Total Hip Arthroplasty".
PMID- 27491446
TI - Damage Patterns at the Head-Stem Taper Junction Helps Understand the Mechanisms
of Material Loss.
AB - BACKGROUND: Material loss at the taper junction of metal-on-metal total hip
arthroplasties has been implicated in their early failure. The mechanisms of
material loss are not fully understood; analysis of the patterns of damage at the
taper can help us better understand why material loss occurs at this junction.
METHODS: We mapped the patterns of material loss in a series of 155 metal-on
metal total hip arthroplasties received at our center by scanning the taper
surface using a roundness-measuring machine. We examined these material loss maps
to develop a 5-tier classification system based on visual differences between
different patterns. We correlated these patterns to surgical, implant, and
patient factors known to be important for head-stem taper damage. RESULTS: We
found that 63 implants had "minimal damage" at the taper (material loss <1 mm3),
and the remaining 92 implants could be categorized by 4 distinct patterns of
taper material loss. We found that (1) head diameter and (2) time to revision
were key significant variables separating the groups. CONCLUSION: These material
loss maps allow us to suggest different mechanisms that dominate the cause of the
material loss in each pattern: (1) corrosion, (2) mechanically assisted
corrosion, or (3) intraoperative damage or poor size tolerances leading to
toggling of trunnion in taper.
PMID- 27491447
TI - The European Knee Society, the Trans-Atlantic Counterpart of the American Knee
Society.
PMID- 27491448
TI - Letter to the Editor on "Large Metal Heads and Vitamin E Polyethylene Increase
Frictional Torque in Total Hip Arthroplasty".
PMID- 27491449
TI - Day of Surgery and Surgical Start Time Affect Hospital Length of Stay After Total
Hip Arthroplasty.
AB - BACKGROUND: The United States spends $12 billion each year on ~332,000 total hip
arthroplasty (THA) procedures with the postoperative period accounting for ~40%
of costs. The purpose of this study was to evaluate the effect of surgical
scheduling (day of week and start time) on clinical outcomes, hospital length of
stay (LOS), and rate of nonhome discharge in THA patients. METHODS: Analysis of
perioperative variables was performed for patients who underwent THA at an urban
tertiary care teaching hospital from 2009 to 2014. RESULTS: A total of 580 THA
patients were included for analysis. LOS was higher for the Thursday/Friday
cohort compared to Monday/Tuesday (3.7 vs 3.4 days; P = .03). Patients who had a
surgical start time after 2 PM had longer LOS compared to patients operated on
before 2 PM (3.9 vs 3.5 days; P = .03). After controlling for patient
comorbidities and THA surgical approach (direct anterior vs posterior),
Thursday/Friday THAs were associated with a 3.27 times risk of extended LOS
(>75th percentile LOS) compared to Monday/Tuesday THAs (P < .001). Additionally,
case start before 2 PM was protective and associated with a 0.46 times odds of
extended LOS (P = .01). LOS reduction opportunity for changing surgical start
time to before 2 PM was 0.9 days for high-risk patients (American Society of
Anesthesiology class 3/4 and/or liver disease) and 0.2 days for low-risk patients
(American Society of Anesthesiology class 1/2). CONCLUSION: Patients who
underwent THA Thursday/Friday or had start times after 2 PM had significantly
extended hospital LOS. Preoperative risk modification along with adjustments to
surgical scheduling and/or perioperative staffing may reduce LOS and thus
hospital expenditures for THA procedures.
PMID- 27491450
TI - Resource allocation and post-reproductive degeneration in the freshwater
cnidarian Hydra oligactis (Pallas, 1766).
AB - Freshwater hydra are among the few animal groups that show negligible senescence
and can maintain high survival and reproduction rates when kept under stable
conditions in the laboratory. Yet, one species of Hydra (H. oligactis) undergoes
a senescence-like process in which polyps degenerate and die after sexual
reproduction. The ultimate factors responsible for this phenomenon are unclear.
High mortality in reproducing animals could be the consequence of increased
allocation of resources to reproduction at the expense of somatic maintenance.
This hypothesis predicts that patterns of reproduction and survival are
influenced by resource availability. To test this prediction we investigated
survival and reproduction at different levels of food availability in 10 lineages
of H. oligactis derived from a single Hungarian population. Sexual reproduction
was accompanied by reduced survival, but a substantial proportion of animals
regenerated after sexual reproduction and continued reproducing asexually. Polyps
belonging to different lineages showed differences in their propensity to
initiate sexual reproduction, gonad number and survival rate. Food availability
significantly affected fecundity (number of eggs or testes produced), with the
largest number of gonads being produced by animals kept on a high food regime. On
the other hand, survival rate was not affected by the amount of food. These
results show that survival is conserved at the expense of reproduction in this
population when food is low. It remains a question still to be answered why
survival is prioritized over reproduction in this population.
PMID- 27491451
TI - Determination of Double Bond Positions and Geometry of Methyl Linoleate Isomers
with Dimethyl Disulfide Adducts by GC/MS.
AB - The dimethyl disulfide (DMDS) adduct method is one of the convenient and
effective methods for determining double bond positions of unsaturated fatty acid
methyl esters (FAME) except conjugated FAME. When analyzed using gas
chromatography/electron ionization-mass spectrometry (GC/EI-MS), unsaturated FAME
with DMDS added to the double bonds yields high intensity MS spectra of
characteristic ions. The MS spectra of characteristic ions can then be used to
easily confirm double bond positions. Here we explore the GC/EI-MS analysis of
the DMDS adducts of methyl linoleate geometrical isomers isolated by high
performance liquid chromatography (HPLC) with a silver nitrate column. For C18:2
c9, c12 and C18:2-t9, t12, DMDS randomly formed adducts with double bonds at
either carbon 9-10 or carbon 12-13, but not both at the same time due to steric
hindrance. For C18:2-c9, t12 and C18:2-t9, c12, however, DMDS only formed adducts
with the double bond in the cis configuration. Consequently, when analyzing fatty
acids with methylene interrupted double bonds, with one double bond in the cis
and one in the trans configuration, double bond positions cannot be completely
confirmed.
PMID- 27491452
TI - Household composition and psychological health: Results of the Second Diabetes
Attitudes, Wishes and Needs (DAWN2) study.
AB - AIMS: 1) To explore the effect of household composition on the psychological
health of adults with diabetes by comparing those living with other adult(s)
including a partner with those living with neither partner nor other adult(s); 2)
to examine potential mediation of social support in the association between
household composition and psychological health. METHODS: The study is part of the
DAWN2 study conducted in 17 countries. The population comprised 8596 people with
diabetes (PWD). Multiple regression models (linear and binary) were applied.
RESULTS: People living with 'other adult(s) but no partner' experienced
significantly lower well-being, higher diabetes distress and worried more
frequently about hypoglycaemic events than those with a partner or those not co
habiting with another adult. However, participants living with 'other adult(s)
but no partner' were more empowered compared to the other household composition
groups. The association between household composition and psychological health
was not mediated by diabetes-specific social support. CONCLUSIONS: The study
indicates the psychological vulnerability of respondents living without a partner
but with other adult(s). Appropriate support interventions must be developed and
tested in order to enhance psychological health in people with diabetes living
with other adults such as adult children, but with no partner.
PMID- 27491453
TI - Comparing DTL microfiber and Neuroline skin electrode in the Mini Ganzfeld ERG.
AB - BACKGROUND: In infant ERG recordings skin electrodes frequently result in a
better compliance. In order to assess the quality of such recordings, we compared
the recording characteristics of DTL microfiber and Neuroline surface electrodes
using a modified ISCEV protocol in the Mini Ganzfeld ERG. METHODS: A prospective
cohort study on healthy adult subjects was conducted at the Department of
Ophthalmology, University of Basel, Switzerland. Thirty healthy volunteers were
tested. The microfiber electrode (DTL Plus Electrode) was placed across the
cornea, above the lower eyelid. The Neuroline skin electrode was placed on the
surface of the lower lid on the opposite eye. The eye on which each electrode
type was placed was randomised. Amplitudes of the rod, standard combined,
standard flash cone, light-adapted 3.0 Hz flicker and red cone responses were
analysed, as well as their respective implicit times. RESULTS: Both electrode
recordings showed the same waveform characteristics. Responses with the Neuroline
electrode were significantly weaker than those from the DTL electrode. Amplitudes
of the rod, standard combined, standard flash cone, light-adapted 3.0 Hz flicker
and red cone responses were up to four times larger when recorded with the DTL
electrode (p < 0.005, ANOVA). Implicit times of the red cone ERGs were slightly
faster for the Neuroline skin electrode recordings (p <= 0.039). CONCLUSIONS:
Comparison of full-field ERG recordings with microfiber DTL and Neuroline skin
electrodes showed that DTL electrodes produce larger ERGs. Hence, we provide
evidence that both electrode types allow successful full-field ERG recording,
although separate normative data for both electrodes are necessary.
PMID- 27491454
TI - Molecular and antimicrobial susceptibility profiling of atypical Streptococcus
species from porcine clinical specimens.
AB - The Streptococcus species present broad phenotypic variation, making
identification difficult using only traditional microbiological methods. Even
though Streptococcus suis is the most important species for the worldwide swine
industry, other Streptococcus species appear to be able to cause disease in swine
and could represent a higher underestimated risk for porcine health. The aim of
this study was to identify Streptococcus-like isolates by MALDI-TOF MS and 16S
rRNA sequencing and further molecular and antibiotic susceptibility
characterization of the atypical Streptococcus species capable of causing disease
in swine. Fifty presumptive Streptococcus isolates from diseased pigs isolated
from different Brazilian States between 2002 and 2014 were evaluated. Among the
studied isolates, 26% were identified as Streptococcus hyovaginalis, 24% as
Streptococcus plurianimalium, 12% as Streptococcus alactolyticus, 10% as
Streptococcus hyointestinalis, and the remaining isolates belonged to
Streptococcus henryi (6%), Streptococcus thoraltensis (6%), Streptococcus
gallolyticus (6%), Streptococcus gallinaceus (4%), Streptococcus sanguinis (4%),
and Streptococcus mitis (2%). The Streptococcus isolates were successfully
identified by spectral cluster analysis and 16S rRNA sequencing with 96% of
concordance between the techniques. The SE-AFLP analysis also supported
Streptococcus species distinction and enabled further observation of higher
genetic heterogeneity intra-species. The identified Streptococcus species
presented variable MIC values to beta-lactams, enrofloxacin and florfenicol, and
high resistance rates to tetracyclines and macrolides, which appear to be
directly related to the industry's antimicrobial usage and resistance selection.
PMID- 27491456
TI - Clinico-epidemiology and genetic diversity of Salivirus in acute gastroenteritis
cases from Pune, Western India: 2007-2011.
AB - Acute gastroenteritis is a leading cause of mortality in children from developing
countries. Recently, Salivirus has been frequently detected in acute
gastroenteritis patients, suggesting its possible aetiological role. Conflicting
reports available on disease association of Salivirus have made it difficult to
ascertain their causative role. The overall epidemiology and clinical features of
Salivirus infections are poorly understood. The present five year study was
undertaken to investigate the presence and genetic diversity of Salivirus in
acute gastroenteritis cases from Pune, Western India and to determine the clinico
epidemiological features of Salivirus infections. A total of 985 faecal samples
(778 acute gastroenteritis and 207 asymptomatic controls), collected from three
local hospitals (Jan2007-Dec2011) were examined for the presence of Salivirus by
RT-PCR. Molecular characterization was performed by PCR amplification of the 3D
and VP regions. Frequency of Salivirus detection in cases (2.6%) and controls
(1.93%) was not significantly different (p = 0.57). Co-infection with other
enteric viruses was seen in 50% of the cases. Comparison of clinical features
between Salivirus mono and mixed infections revealed that Salivirus alone did not
exacerbate gastroenteritis. The frequency of diarrhoea and overall clinical
severity of mixed infections was significantly greater than mono infections (p =
0.02). Based on clinical findings, our study suggests that Salivirus does not
cause severe gastroenteritis. Phylogenetic analysis indicated that study strains
belonged to Salivirus A1 and formed 2 distinct clusters which shared nucleotide
identities of 94.1-96.2% and 88.9-93.8% between themselves in 3D and VP regions,
respectively. Interestingly, the more divergent Cluster2 strains shared a low
nucleotide identity with the closest reference strain in both regions (~95% in 3D
and ~92% in VP) suggesting that they could represent a variant type of Salivirus
A1. The genetic diversity in strains detected from study region, emphasizes the
need for Salivirus surveillance from other regions of India.
PMID- 27491455
TI - Strong down-regulation of glycophorin genes: A host defense mechanism against
rotavirus infection.
AB - The mechanisms of rotavirus (RV) infection have been analyzed from different
angles but the way in which RV modifies the transcriptome of the host is still
unknown. Whole transcriptome shotgun sequencing of peripheral blood samples was
used to reveal patterns of expression from the genome of RV-infected patients. RV
provokes global changes in the transcriptome of infected cells, involving an over
expression of genes involved in cell cycle and chromatin condensation. While
interferon IFI27 was hyper-activated, interferon type II was not suggesting that
RV has developed mechanisms to evade the innate response by host cells after
virus infection. Most interesting was the inhibition of genes of the glycophorins
A and B (GYPA/B) family, which are the major sialoglycoproteins of the human
erythrocyte membrane and receptor of several viruses for host invasion. RV
infection induces a complex and global response in the host. The strong
inhibition of glycophorins suggests a novel defense mechanism of the host to
prevent viral infection, inhibiting the expression of receptors used by the virus
for infection. The present results add further support to the systemic nature of
RV infection.
PMID- 27491457
TI - Genetic variants in the regulatory region of SLC10A1 are not associated with the
risk of hepatitis B virus infection and clearance.
AB - The Na/taurocholate cotransporter NTCP (encoded by SLC10A1) was identified as a
cellular entry receptor for the human hepatitis B virus (HBV), advancing our
understanding of the molecular mechanism of HBV infection. An alternative
hypothesis was put forward that regulatory variants in SLC10A1 might play an
important role in HBV susceptibility by potentially influencing expression levels
of NTCP. The three regulatory SNPs (rs8011311, rs7154439, rs111409076) were
genotyped in 1023 HBV-persistent carriers, 735 subjects with HBV natural
clearance and 732 HBV marker-negative subjects in a Han Chinese population. Real
time reverse transcription PCR analysis and luciferase assays have been performed
to dissect the potential functionality. In logistic regression analysis, when
subjects with HBV natural clearance were compared with HBV marker-negative
subjects, no significant associations with the risk of HBV infection were
observed for any of the three SNPs after adjusting for age, sex, smoking status
and alcohol consumption (P>0.05). Similar negative results were also found for
the three SNPs when HBV-persistent carriers were compared with HBV marker
negative subjects. Likewise, no significant associations with the risk of HBV
clearance were observed when HBV-persistent carriers were compared with subjects
with HBV natural clearance (P>0.05). Quantitative RT/PCR showed no significant
difference in NTCP expression levels in normal liver tissue amongst individuals
with different rs111409076 genotypes (P=0.317 for the general linear model).
Moreover, no evident effect of the SLC10A1 rs111409076 AACA/- polymorphism on
transcriptional activity was found by luciferase assay in either HepG2 (P=0.161)
or Hep3b (P=0.129) cell lines. The present study indicated that the common
variants in the regulatory region of SLC10A1 may not influence the expression of
NTCP at the level of transcriptional regulation, and ultimately may not be
associated with HBV susceptibility in this Chinese population.
PMID- 27491458
TI - Zoonotic trypanosomes in South East Asia: Attempts to control Trypanosoma lewisi
using human and animal trypanocidal drugs.
AB - Beside typical human trypanosomes responsible of sleeping sickness in Africa and
Chagas disease in Latin America, there is a growing number of reported atypical
human infections due to Trypanosoma evansi, a livestock parasite, or Trypanosoma
lewisi, a rat parasite, especially in Asia. Drugs available for the treatment of
T. brucei ssp. in humans are obviously of choice for the control of T. evansi
because it is derived from T. brucei. However, concerning T. lewisi, there is an
urgent need to determine the efficacy of trypanocidal drugs for the treatment in
humans. In a recent study, pentamidine and fexinidazole were shown to have the
best efficacy against one stock of T. lewisi in rats. In the present study
suramin, pentamidine, eflornitine, nifurtimox, benznidazole and fexinidazole,
were evaluated at low and high doses, in single day administration to normal rats
experimentally infected with a stock of T. lewisi recently isolated in Thailand.
Because none of these treatments was efficient, a trial was made with the most
promising trypanocide identified in a previous study, fexinidazole 100mg/kg, in 5
daily administrations. Results observed were unclear. To confirm the efficacy of
fexinidazole, a mixed infection protocol was set up in cyclophosphamide
immunosuppressed rats. Animals were infected successively by T. lewisi and T.
evansi, and received 10 daily PO administrations of 200mg/kg fexinidazole.
Drastic effects were observed against T. evansi which was cleared from the rat's
blood within 24 to 48h; however, the treatment did not affect T. lewisi which
remained in high number in the blood until the end of the experiment. This mixed
infection/treatment protocol clearly demonstrated the efficacy of fexinidazole
against T. evansi and its inefficacy against T. lewisi. Since animal trypanocides
were also recently shown to be inefficient, other protocols as well as other T.
lewisi stocks should be investigated in further studies.
PMID- 27491459
TI - Stent-assisted coiling of very small wide-necked intracranial aneurysms:
Complications, anatomical results and clinical outcomes.
AB - BACKGROUND AND OBJECTIVE: Treatment of very small (<=3mm) wide-necked
intracranial aneurysms remains controversial, we investigated the efficacy and
safety of stent-assisted coiling of such aneurysms. METHODS: From September 2008
to December 2012, 112 very small wide-necked intracranial aneurysms in 108
patients were embolized with stent-assisted coiling. We assessed the initial
neurological conditions, complications and anatomic results. The follow-up
results were evaluated with DSA and mRS. RESULTS: Stent deployment was successful
in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during
procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism.
The rate of complication, rupture and thromboembolism was not statistically
different between the ruptured and unruptured patients (P=0.452, P=0.369,
P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1
in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients
(19.4%). 79 aneurysms were available for anatomic follow-up of 12-47 months,
stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34
aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of
12-52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS <=2), 3
patients (3.2%) had morbidity (mRS: 3-5). The morbidity was not statistically
different between the ruptured and unruptured patients (P=1.000). CONCLUSIONS:
Stent-assisted coiling of very small wide-necked intracranial aneurysms may be
effective and safe. Because of low risk of rupture in such aneurysms, the coiling
of unruptured such aneurysms must be selective. The long-term efficacy and safety
of coiling such aneurysms remains to be determined in larger prospective series.
PMID- 27491461
TI - Preconception weight management: an untapped area of women's health.
AB - The aim of this study was to identify barriers to providing preconception weight
management. Twenty health professionals participated in a semistructured phone
interview regarding their beliefs on perceived barriers to providing
preconception weight management. The interviews were recorded, transcribed
verbatim and examined using thematic analysis to extract the key themes. Two
themes were identified from the interviews: (1) barriers hindering women from
accessing preconception weight management interventions (i.e. women's lack of
awareness regarding the importance of preconception weight, and not being
provided with weight management information or interventions by health
professionals); and (2) barriers preventing health professionals from providing
preconception weight management (i.e. an absence of implementation resources for
preconception weight management, limited access to women of childbearing age who
plan to conceive, and a high percentage of pregnancies being unplanned). There
are significant client- and heath professional-based barriers to implementing
preconception weight management. To begin to address these barriers, developing
policy and preconception weight management programs based on evidence collected
via a needs assessment, quantitative or mixed-method designs may be of benefit.
Furthermore, these barriers are likely contributing to the paucity in research
into preconception weight management services.
PMID- 27491460
TI - Improvement of quality of life after therapeutic plasma exchange in patients with
myasthenic crisis.
AB - INTRODUCTION: We sought to evaluate quality of life patients with myasthenic
crisis before and after therapeutic plasma exchange. MATERIALS AND METHODS: In
our study we conducted an assessment of the quality of life with the use of the
questionnaire SF-36, when executed eleven therapeutic plasma exchange. The
assessment was made on baseline and after 4 weeks. We also did neurological
clinical evaluation before and after TPE. RESULTS: Patients in the study showed
significant improvement in quality of life after performed therapeutic plasma
exchange. The changes were observed in physical functioning, which confirmed the
results of the statistical significance of p<0.05. In the analysis, the
assessment of mental functioning not obtained the results of statistical
significance, but the results also showed improvement in self-assessment. We
observed high correlation between general health and physical mental functioning,
between the role limitations due to physical health problems and role limitations
due to emotional problems, and general health perception and bodily pain.
CONCLUSIONS: Therapeutic plasma exchange significantly improves the quality of
life of patients with myasthenia gravis during the crisis.
PMID- 27491462
TI - Dialysis-Related Spondyloarthropathy with Cervical Amyloidoma.
PMID- 27491463
TI - Intestinal Angioedema in a Palliative Care Setting.
PMID- 27491464
TI - Hospital Accreditation and Community Health.
PMID- 27491465
TI - Digital Medicine: "O Brave New World".
PMID- 27491466
TI - Intermittent Gastric Volvulus Mimicking Acute Coronary Syndrome.
PMID- 27491468
TI - Changing Times in Cardiovascular Publications: A Commentary.
PMID- 27491467
TI - A Case Report of Delayed Return of Spontaneous Circulation: Lazarus Phenomenon.
PMID- 27491469
TI - Massive Spontaneous Subcutaneous Emphysema.
PMID- 27491471
TI - Lack of existing guidelines for a large group of patients in Sweden: a national
survey across the acute surgical care delivery chain.
AB - RATIONALE, AIMS AND OBJECTIVES: Evidence-informed healthcare is the fundament for
practice, whereby guidelines based on the best available evidence should assist
health professionals in managing patients. Patients seeking care for acute
abdominal pain form a common group in acute care settings worldwide, for whom
decision-making and timely treatment are of paramount importance. There is
ambiguity about the existence, use and content of guidelines for patients with
acute abdomen. The objective was to describe and compare guidelines and
management of patients with acute abdomen in different settings across the acute
care delivery chain in Sweden. METHOD: A national cross-sectional design was
used. Twenty-nine ambulance stations, 17 emergency departments and 33 surgical
wards covering all six Swedish health regions were included, and 23 guidelines
were quality appraised using the validated Appraisal of Guidelines for Research &
Evaluation II tool. RESULTS: There is a lack of guidelines in use for the
management of this large group of patients between and within different
healthcare areas across the acute care delivery chain. The quality appraisal
identified that several guidelines were of poor quality, especially the in
hospital ones. Further, range orders for analgesics are common in the ambulance
services and the surgical wards, but are seldom present in the emergency
departments. Also, education in pain management is more common in the ambulance
services. These findings are noteworthy as, hypothetically, the same patient
could be treated in three different ways during the same care episode.
CONCLUSIONS: There is an urgent need to develop high-quality evidence-based
clinical guidelines for this patient group, with the entire care process in
focus.
PMID- 27491470
TI - Including alpha s1 casein gene information in genomic evaluations of French dairy
goats.
AB - BACKGROUND: Genomic best linear unbiased prediction methods assume that all
markers explain the same fraction of the genetic variance and do not account
effectively for genes with major effects such as the alpha s1 casein polymorphism
in dairy goats. In this study, we investigated methods to include the available
alpha s1 casein genotype effect in genomic evaluations of French dairy goats.
METHODS: First, the alpha s1 casein genotype was included as a fixed effect in
genomic evaluation models based only on bucks that were genotyped at the alpha s1
casein locus. Less than 1 % of the females with phenotypes were genotyped at the
alpha s1 casein gene. Thus, to incorporate these female phenotypes in the genomic
evaluation, two methods that allowed for this large number of missing alpha s1
casein genotypes were investigated. Probabilities for each possible alpha s1
casein genotype were first estimated for each female of unknown genotype based on
iterative peeling equations. The second method is based on a multiallelic gene
content approach. For each model tested, we used three datasets each divided into
a training and a validation set: (1) two-breed population (Alpine + Saanen), (2)
Alpine population, and (3) Saanen population. RESULTS: The alpha s1 casein
genotype had a significant effect on milk yield, fat content and protein content.
Including an alpha s1 casein effect in genetic and genomic evaluations based only
on male known alpha s1 casein genotypes improved accuracies (from 6 to 27 %). In
genomic evaluations based on all female phenotypes, the gene content approach
performed better than the other tested methods but the improvement in accuracy
was only slightly better (from 1 to 14 %) than that of a genomic model without
the alpha s1 casein effect. CONCLUSIONS: Including the alpha s1 casein effect in
a genomic evaluation model for French dairy goats is possible and useful to
improve accuracy. Difficulties in predicting the genotypes for ungenotyped
animals limited the improvement in accuracy of the obtained estimated breeding
values.
PMID- 27491473
TI - Deprescription in Advanced Cancer Patients Referred to Palliative Care.
AB - In palliative care, drugs are considered futile if they do not have a short-term
benefit in symptom control or quality of life. The authors examined
pharmacotherapy prescribed for patients referred to palliative care to identify
futile drugs. This was a retrospective analysis of patients referred over 6
months, focusing on the prescription of gastric protectants, antidiabetic agents,
bisphosphonates, anticoagulants, antidementia drugs, statins, and
antihypertensive agents. The sample consisted of 448 patients. Gastric
protectants were prescribed futilely in 50% of cases (125/248), statins in 97%
(69/71), antihypertensive agents in 27% (42/155), antidiabetic drugs in 1%
(1/70), bisphosphonates in 27% (4/15), and antidementia drugs in 100% (9/9). This
study reveals that many patients with advanced cancer continue to be treated with
inappropriate drugs and points to the need for medical training in palliative
care, drawing attention to the need for therapeutic review at each medical visit.
PMID- 27491472
TI - Serum gamma-glutamyltransferase is not associated with subclinical
atherosclerosis in patients with type 2 diabetes.
AB - BACKGROUND: This study investigated the association between serum gamma
glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with
type 2 diabetes. METHODS: This cross-sectional study involved 1024 patients with
type 2 diabetes mellitus. Measurement of brachial-ankle pulse wave velocity
(baPWV; as a marker of arterial stiffness) and an ultrasound assessment of
carotid atherosclerosis were performed. Subclinical atherosclerosis was defined
by the presence of a high baPWV (>=1720 cm/s), carotid atherosclerosis (intima
media thickness >0.8 mm or the presence of plaques), and carotid stenosis (>=50 %
of luminal narrowing). The subjects were stratified into quartiles according to
GGT level, and the relationship between GGT level and subclinical atherosclerosis
was analysed. RESULTS: Serum GGT levels were closely associated with obesity,
atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did
not show a linear association with baPWV, carotid intima-media thickness, or
plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid
stenosis did not differ between the quartiles in men and women. Multivariate
logistic regression analyses revealed no association between GGT level and high
baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous
variables or quartiles. CONCLUSIONS: Serum GGT levels were significantly
associated with obesity, atherogenic dyslipidaemia, and metabolic syndrome, but
not with the early and late stages of atherosclerotic vascular changes, in
patients with type 2 diabetes. Serum GGT level may not be a reliable marker of
subclinical atherosclerosis in type 2 diabetes.
PMID- 27491474
TI - Fractions Learning in Children With Mathematics Difficulties.
AB - Learning fractions is difficult for children in general and especially difficult
for children with mathematics difficulties (MD). Recent research on developmental
and individual differences in fraction knowledge of children with MD and
typically achieving (TA) children has demonstrated that U.S. children with MD
start middle school behind their TA peers in fraction understanding and fall
further behind during middle school. In contrast, Chinese children, who like the
MD children in the United States score in the bottom one third of the
distribution in their country, possess reasonably good fraction understanding. We
interpret these findings within the framework of the integrated theory of
numerical development. By emphasizing the importance of fraction magnitude
knowledge for numerical understanding in general, the theory proved useful for
understanding differences in fraction knowledge between MD and TA children and
for understanding how knowledge can be improved. Several interventions
demonstrated the possibility of improving fraction magnitude knowledge and
producing benefits that generalize to fraction arithmetic learning among children
with MD. The reasonably good fraction understanding of Chinese children with MD
and several successful interventions with U.S. students provide hope for the
improvement of fraction knowledge among American children with MD.
PMID- 27491475
TI - The association between multiple sclerosis and uveitis.
AB - The association between multiple sclerosis (MS) and uveitis has been questioned.
Nerve tissue and eye tissue develop from the same embryonic cells; thus, MS and
uveitis could be etiologically associated. In published studies, the prevalence
of MS in patients with uveitis differe from 0.7% to 30.4%, whereas the prevalence
of uveitis in patients with MS differe from 0.65% to 36.7%. Based on the largest
retrospective studies, the prevalence of uveitis among MS patients is ~1%, and
the prevalence of MS among patients with uveitis is ~1%. This is considerably
higher than in the general population; thus, more research on this topic is
needed to further understand the relationship between MS and uveitis.
PMID- 27491476
TI - Controversies over the role of internal limiting membrane peeling during
vitrectomy in macular hole surgery.
AB - Surgical management of an idiopathic macular hole consists of vitrectomy to
release vitreofoveal traction and intraocular tamponade to flatten and reappose
the hole's edges. The intentional atraumatic removal of the internal limiting
membrane has been proposed as cost-effective option in macular hole surgery. The
internal limiting membrane contributes to tangential traction at the edges of the
hole and acts as a platform on which glial cells proliferate. Removal of the
internal limiting membrane increases the elasticity of the denuded macula and
improves the anatomical success rate; however, the visual consequences of this
surgical maneuver are still not fully known. We discuss the beneficial and
adverse effects associated with internal limiting membrane peeling in macular
hole surgery, highlighting the internal limiting membrane's role in macular hole
etiology and pathogenesis and the anatomical and functional findings after its
removal.
PMID- 27491477
TI - Revisiting the interpretation of casein micelle SAXS data.
AB - An in-depth, critical review of model-dependent fitting of small-angle X-ray
scattering (SAXS) data of bovine skim milk has led us to develop a new
mathematical model for interpreting these data. Calcium-edge resonant soft X-ray
scattering data provides unequivocal evidence as to the shape and location of the
scattering due to colloidal calcium phosphate, which is manifested as a
correlation peak centred at q = 0.035 A(-1). In SAXS data this feature is seldom
seen, although most literature studies attribute another feature centred at q =
0.08-0.1 A(-1) to CCP. This work shows that the major SAXS features are due to
protein arrangements: the casein micelle itself; internal regions approximately
20 nm in size, separated by water channels; and protein structures which are
inhomogeneous on a 1-3 nm length scale. The assignment of these features is
consistent with their behaviour under various conditions, including hydration
time after reconstitution, addition of EDTA (a Ca-chelating agent), addition of
urea, and reduction of pH.
PMID- 27491478
TI - Cognitive inflexibility in Obsessive-Compulsive Disorder.
AB - Obsessive-Compulsive Disorder (OCD) is characterized by maladaptive patterns of
repetitive, inflexible cognition and behavior that suggest a lack of cognitive
flexibility. Consistent with this clinical observation, many neurocognitive
studies suggest behavioral and neurobiological abnormalities in cognitive
flexibility in individuals with OCD. Meta-analytic reviews support a pattern of
cognitive inflexibility, with effect sizes generally in the medium range.
Heterogeneity in assessments and the way underlying constructs have been
operationalized point to the need for better standardization across studies, as
well as more refined overarching models of cognitive flexibility and executive
function (EF). Neuropsychological assessments of cognitive flexibility include
measures of attentional set shifting, reversal and alternation, cued task
switching paradigms, cognitive control measures such as the Trail-Making and
Stroop tasks, and several measures of motor inhibition. Differences in the
cognitive constructs and neural substrates associated with these measures suggest
that performance within these different domains should be examined separately.
Additional factors, such as the number of consistent trials prior to a shift and
whether a shift is explicitly signaled or must be inferred from a change in
reward contingencies, may influence performance, and thus mask or accentuate
deficits. Several studies have described abnormalities in neural activation in
the absence of differences in behavioral performance, suggesting that our
behavioral probes may not be adequately sensitive, but also offering important
insights into potential compensatory processes. The fact that deficits of
moderate effect size are seen across a broad range of classic neuropsychological
tests in OCD presents a conceptual challenge, as clinical symptomatology suggests
greater specificity. Traditional cognitive probes may not be sufficient to
delineate specific domains of deficit in this and other neuropsychiatric
disorders; a new generation of behavioral tasks that test more specific
underlying constructs, supplemented by neuroimaging to provide insight into the
underlying processes, may be needed.
PMID- 27491480
TI - The integrated ultradian organization of behavior and physiology in mice and the
contribution of orexin to the ultradian patterning.
AB - Our series of rat experiments have shown that locomotor activity, arousal level,
body and brown adipose tissue temperatures, heart rate and arterial pressure
increase episodically in an integrated manner approximately every 100min
(ultradian manner). Although it has been proposed that the integrated ultradian
pattern is a fundamental biological rhythm across species, there are no reports
of the integrated ultradian pattern in species other than rats. The aim of the
present study was to establish a mouse model using simultaneous recording of
locomotor activity, eating behavior, body temperature, heart rate and arousal in
order to determine whether their behavior and physiology are organized in an
ultradian manner in normal (wild-type) mice. We also incorporated the same
recording in prepro-orexin knockout (ORX-KO) mice to reveal the role of orexin in
the brain mechanisms underlying ultradian patterning. The orexin system is one of
the key conductors required for coordinating autonomic functions and behaviors,
and thus may contribute to ultradian patterning. In wild-type mice, locomotor
activity, arousal level, body temperature and heart rate increased episodically
every 93+/-18min (n=8) during 24h. Eating was integrated into the ultradian
pattern, commencing 23+/-4min (n=8) after the onset of an electroencephalogram
(EEG) ultradian episode. The integrated ultradian pattern in wild-type mice is
very similar to that observed in rats. In ORX-KO mice, the ultradian episodic
changes in locomotor activity, EEG arousal indices and body temperature were
significantly attenuated, but the ultradian patterning was preserved. Our
findings support the view that the ultradian pattern is common across species.
The present results also suggest that orexin contributes to driving ultradian
episodic changes, however, this neuropeptide is not essential for the generation
of the ultradian pattern.
PMID- 27491479
TI - Lateralized motor control processes determine asymmetry of interlimb transfer.
AB - This experiment tested the hypothesis that interlimb transfer of motor
performance depends on recruitment of motor control processes that are
specialized to the hemisphere contralateral to the arm that is initially trained.
Right-handed participants performed a single-joint task, in which reaches were
targeted to 4 different distances. While the speed and accuracy was similar for
both hands, the underlying control mechanisms used to vary movement speed with
distance were systematically different between the arms: the amplitude of the
initial acceleration profiles scaled greater with movement speed for the right
dominant arm, while the duration of the initial acceleration profile scaled
greater with movement speed for the left-non-dominant arm. These two processes
were previously shown to be differentially disrupted by left and right hemisphere
damage, respectively. We now hypothesize that task practice with the right arm
might reinforce left-hemisphere mechanisms that vary acceleration amplitude with
distance, while practice with the left arm might reinforce right-hemisphere
mechanisms that vary acceleration duration with distance. We thus predict that
following right arm practice, the left arm should show increased contributions of
acceleration amplitude to peak velocities, and following left arm practice, the
right arm should show increased contributions of acceleration duration to peak
velocities. Our findings support these predictions, indicating that asymmetry in
interlimb transfer of motor performance, at least in the task used here, depends
on recruitment of lateralized motor control processes.
PMID- 27491481
TI - Phase II trial of neoadjuvant letrozole and lapatinib in Asian postmenopausal
women with estrogen receptor (ER) and human epidermal growth factor receptor 2
(HER2)-positive breast cancer [Neo-ALL-IN]: Highlighting the TILs, ER
expressional change after neoadjuvant treatment, and FES-PET as potential
significant biomarkers.
AB - PURPOSE: Neo-ALL-IN (NCT 01275859) is a single-center, phase II study aimed to
evaluate the efficacy and safety profiles of neoadjuvant letrozole plus
lapatinib, as well as potential biomarkers, in postmenopausal women with ER- and
HER2-positive (ER+HER2+) breast cancer. METHODS: Postmenopausal ER+HER2+ breast
cancer of stages II-III was eligible. Daily 2.5 mg letrozole plus 1500 mg
lapatinib were administered for 18-21 weeks before surgery. Clinical responses
were assessed by palpation with caliper, breast ultrasonography, mammogram,
and/or MRI. Biologic samples were collected for biomarker analyses at three time
points (baseline, day 14, and before surgery). Baseline fluorine-18
fluorodeoxyglucose and fluorine-18 fluoroestradiol PET-CT scans were performed.
RESULTS: Among 24 patients enrolled, 17 (70.8 %) completed planned neoadjuvant
treatment, whereas 7 prematurely terminated the treatment and proceeded to
surgery because of toxicity or progression; 2 patients showed definite
progression, and 2 showed clinical regrowth by palpation regardless of minimal
response. All patients eventually underwent breast cancer surgery. Toxicities
were generally mild mostly within grades 1-2 except prolonged or recurrent grade
3 liver toxicities in 3 patients (13.6 %) regardless of sequential dose
reduction, which finally led to discontinuation of treatment. The overall
clinical response rates were 62.5 % (n = 15) including 1 CR in breast. However,
no pathologic CR (ypT0-is N0) was achieved. SUVmax lower than 5.5 in baseline FES
PET-CT (p = 0.007), baseline TILs over 20 % (p = 0.026), and decreased IHC ER
Allred score after neoadjuvant treatment (p = 0.021) were significantly
associated with adverse clinical response. CONCLUSIONS: When this chemo-free,
combination neoadjuvant therapy with letrozole and lapatinib is given for Asian
postmenopausal ER+HER2+ breast cancer, TILs, change of ER expression following
neoadjuvant treatment, and SUVmax in baseline FES-PET are to be considered
potential biomarkers in these patients.
PMID- 27491482
TI - A method for optimizing dosage regimens in oncology by visualizing the safety and
efficacy response surface: analysis of inotuzumab ozogamicin.
AB - PURPOSE: The aim of this investigation was to develop a quantitative method to
optimize inotuzumab ozogamicin (InO) dosage regimen in patients with indolent non
Hodgkin lymphoma (NHL) by simultaneously balancing safety and efficacy. METHODS:
Pharmacokinetics (PK), safety and efficacy data were obtained from a phase 2
trial of InO administered intravenously to patients (n = 81) with indolent NHL.
The PK was described by a two-compartment model which was linked to: (1) an
exponential tumor growth model to describe tumor size time course (efficacy
determinant expressed as objective response rate) and (2) a precursor-dependent
platelet inhibition model to describe platelet time course (safety determinant
expressed as thrombocytopenia grade). The model was used to simulate virtual
trials to construct safety and efficacy response surfaces. Using the simulated
safety and efficacy contours, a clinical utility index (CUI) contour was then
constructed, from which optimal InO regimens were then selected. RESULTS: The
model-simulated efficacy response surface indicated near-optimal efficacy of InO
at the dosage regimen used in the trial (1.8 mg/m(2) every 4 weeks). The model
simulated safety response surface indicated that modifying the dosage regimen
resulted in modest improvements in safety with little compromise in efficacy. The
CUI contour identified 2 mg/m(2) every 10, 11, or 12 weeks as the "sweet spot"
for optimal InO dosage regimen in patients with indolent NHL. CONCLUSION: An
approach to dosage regimen optimization was developed for simultaneously
balancing safety and efficacy. This approach allows objective identification of
optimal dosage regimens from early trial information and thus has broad utility
across oncology trials.
PMID- 27491483
TI - Statistical Mechanical Model for pH-Induced Protein Folding: Application to
Apomyoglobin.
AB - Despite the major role of pH in protein folding and stability, a quantitative
understanding of the pH-induced protein folding mechanism remains elusive. Two
conventional models, the Monod-Wyman-Changeux and Linderstrom-Lang smeared charge
models, respectively, have been used to analyze the formation/disruption of
specific native structures and fluctuating non-native states. However, there are
only a few models that can represent the overall kinetic events of
folding/unfolding independent of the properties of relevant molecular species,
which has hampered the efforts to systematically analyze pH-induced folding.
Here, we constructed a statistical mechanical model that incorporates the
protonation mechanism of conventional models along with a combined manual search
and least-squares fitting procedure, which was used to investigate the folding of
horse apomyoglobin over a wide pH range (2.2-6.7), with a time window ranging
from ~40 MUs to ~100 s, using continuous-/stopped-flow fluorescence at 8 degrees
C. Quantitative analysis assuming a five-state sequential scheme indicated that
(1) pH-induced folding/unfolding is represented by both specific binding and
Coulombic interactions; (2) kinetic folding/unfolding intermediates share kinetic
mechanisms with the equilibrium intermediate, indicating their equivalence; and
(3) native-like properties are acquired successively during folding by
intermediates and in transition states. This model could also be applied to a
variety of association/dissociation processes.
PMID- 27491484
TI - Water ascent in trees and lianas: the cohesion-tension theory revisited in the
wake of Otto Renner.
AB - The cohesion-tension theory of water ascent (C-T) has been challenged over the
past decades by a large body of experimental evidence obtained by means of
several minimum or non-invasive techniques. The evidence strongly suggests that
land plants acquire water through interplay of several mechanisms covered by the
multi-force theory of (U. Zimmermann et al. New Phytologist 162: 575-615, 2004).
The diversity of mechanisms includes, for instance, water acquisition by inverse
transpiration and thermodynamically uphill transmembrane water secretion by
cation-chloride cotransporters (L.H. Wegner, Progress in Botany 76:109-141,
2014). This whole plant perspective was opened by Otto Renner at the beginning of
the last century who supported experimentally the strictly xylem-bound C-T
mechanism, yet anticipated that the water ascent involves both the xylem conduit
and parenchyma tissues. The survey also illustrates the known paradigm that new
techniques generate new insights, as well as a paradigm experienced by Max Planck
that a new scientific idea is not welcomed by the community instantly.
PMID- 27491486
TI - The Case For and Against a Coronary Artery Calcium Trial: Means, Motive, and
Opportunity.
AB - Numerous observational studies have shown that coronary artery calcium (CAC)
imaging can improve cardiovascular risk assessment in asymptomatic adults.
Whether CAC imaging can improve cardiovascular outcomes as part of an overall
risk reduction strategy compared to alternative care approaches has not been
demonstrated in clinical trials. Therefore, the role of CAC imaging in primary
prevention of cardiovascular disease is somewhat contentious. Advocates for
expanded CAC testing offer the large amount of observational data as support for
their position, while opponents to wider CAC testing propose that only a clinical
trial can resolve the matter. This paper reviews the arguments for and against
such a trial based on clinical, safety and economic considerations. We also
propose potential trial approaches based on recent changes in clinical practice
that could make a new CAC trial design feasible.
PMID- 27491485
TI - Safety and Efficacy of Self-Expanding TAVR in Patients With Aortoventricular
Angulation.
AB - OBJECTIVES: The aim of this study was to determine the relationship between
aortoventricular (AoV) angulation on clinical outcomes after self-expanding
transcatheter aortic valve replacement (TAVR) in patients with severe aortic
stenosis who were deemed suboptimal for surgery. BACKGROUND: Multidetector
computed tomographic (MDCT) imaging of the aortovalvular complex has become a
prerequisite for case planning with self-expanding TAVR. The effect of aortic
angulation, an index of an unfolded or "horizontal" aorta, on procedural outcome
after self-expanding TAVR is not known. METHODS: The clinical course of 3,578
patients who received implants in the CoreValve US Clinical Trials and who had
prospective MDCT estimation of the AoV angle before the procedure was reviewed.
Clinical site echocardiogram assessments were used to determine the degree of
residual aortic regurgitation 24 to 48 h after the procedure and at 30 days. On
the basis of the measurement of the AoV angle on MDCT, patients were categorized
into septiles, ranging from the lowest septile of an AoV angle <37.0 degrees to
the highest AoV angle septile of >55.0 degrees . RESULTS: Patients were elderly
(age 83.3 +/- 7.8 years) and were at high risk for surgical valve replacement
(Society of Thoracic Surgeons Predicted Risk of Mortality 8.8 +/- 4.7). Greater
degrees of AoV angulation were correlated with older age (p < 0.0001). Although
procedure time was 6.9 min longer in the highest septile (59.4 +/- 35.9 min vs.
52.5 +/- 35.3 min in the lowest septile; p = 0.004), there were no linear trends
(p > 0.05) in the frequencies of device success, procedural success, frequencies
of moderate or greater aortic regurgitation at 30 days, number of valves
implanted, or need for balloon post-dilation or new pacemakers among the AoV
angle septiles. CONCLUSIONS: The degree of AoV angulation does not affect early
clinical outcomes self-expanding transcatheter aortic valve replacement. (Safety
and Efficacy Study of the Medtronic CoreValve(r) System in the Treatment of
Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who
Need Aortic Valve Replacement [Medtronic CoreValve(r) U.S. Pivotal Trial];
NCT01240902).
PMID- 27491487
TI - Arterial Remodeling and Endothelial Shear Stress Exhibit Significant Longitudinal
Heterogeneity Along the Length of Coronary Plaques.
PMID- 27491488
TI - When Is an Image Telling the Truth? Discordant Lessons From Imaging TAVR.
PMID- 27491489
TI - Heart rate variability during sleep in children with autism spectrum disorder.
AB - PURPOSE: Autonomic dysfunction has been reported in autism spectrum disorders
(ASD). Less is known about autonomic function during sleep in ASD. The objective
of this study is to provide insight into the autonomic cardiovascular control
during different sleep stages in ASD. We hypothesized that patients with ASD have
lower vagal and higher sympathetic modulation with elevated heart rate, as
compared to typical developing children (TD). METHODS: We studied 21 children
with ASD and 23 TD children during overnight polysomnography. Heart rate and
spectral parameters were calculated for each vigilance stage during sleep. Data
from the first four sleep cycles were used to avoid possible effects of different
individual sleep lengths and sleep cycle structures. Linear regression models
were applied to study the effects of age and diagnosis (ASD and TD). RESULTS: In
both groups, HR decreased during non-REM sleep and increased during REM sleep.
However, HR was significantly higher in stages N2, N3 and REM sleep in the ASD
group. Children with ASD showed less high frequency (HF) modulation during N3 and
REM sleep. LF/HF ratio was higher during REM. Heart rate decreases with age at
the same level in ASD and in TD. We found an age effect in LF in REM different in
ASD and TD. CONCLUSION: Our findings suggest possible deficits in vagal influence
to the heart during sleep, especially during REM sleep. Children with ASD may
have higher sympathetic dominance during sleep but rather due to decreased vagal
influence.
PMID- 27491490
TI - A case of idiopathic pure sudomotor failure associated with prolonged high levels
of serum carcinoembryonic antigen.
AB - We report a case of idiopathic pure sudomotor failure (IPSF) in which serum
carcinoembryonic antigen (CEA) levels elevated at onset, and remained high while
anhidrosis lasted. We considered that changes in serum levels of CEA were related
to the disease activity of IPSF.
PMID- 27491491
TI - Mixing positive and negative valence: Affective-semantic integration of bivalent
words.
AB - Single words have affective and aesthetic properties that influence their
processing. Here we investigated the processing of a special case of word stimuli
that are extremely difficult to evaluate, bivalent noun-noun-compounds (NNCs),
i.e. novel words that mix a positive and negative noun, e.g. 'Bombensex' (bomb
sex). In a functional magnetic resonance imaging (fMRI) experiment we compared
their processing with easier-to-evaluate non-bivalent NNCs in a valence decision
task (VDT). Bivalent NNCs produced longer reaction times and elicited greater
activation in the left inferior frontal gyrus (LIFG) than non-bivalent words,
especially in contrast to words of negative valence. We attribute this effect to
a LIFG-grounded process of semantic integration that requires greater effort for
processing converse information, supporting the notion of a valence
representation based on associations in semantic networks.
PMID- 27491492
TI - Sodium P-Aminosalicylic Acid Improved Manganese-Induced Learning and Memory
Dysfunction via Restoring the Ultrastructural Alterations and gamma-Aminobutyric
Acid Metabolism Imbalance in the Basal Ganglia.
AB - Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para
aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn
induced neurotoxicity. The gamma-aminobutyric acid (GABA) is related with
learning and memory abilities. However, the mechanism of PAS-Na on improving Mn
induced behavioral deficits is unclear. The current study was aimed to
investigate the effects of PAS-Na on Mn-induced behavioral deficits and the
involvement of ultrastructural alterations and gamma-aminobutyric acid (GABA)
metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily
intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks,
followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg),
5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn
exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and
these effects were long-lasting. Moreover, Mn exposure caused ultrastructural
alterations in the basal ganglia expressed as swollen neuronal with increasing
the electron density in the protrusions structure and fuzzed the interval of
neuropil, together with swollen, focal hyperplasia, and hypertrophy of
astrocytes. Additionally, the results also indicated that Mn exposure increased
Glu/GABA values as by feedback loops controlling GAT-1, GABAA mRNA and GABAA
protein expression through decreasing GABA transporter 1(GAT-1) and GABA A
receptor (GABAA) mRNA expression, and increasing GABAA protein expression in the
basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na
treatment for 3 or 6 weeks effectively restored the above-mentioned adverse
effects induced by Mn. In conclusion, these findings suggest the involvement of
GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na's
protective effects on the spatial learning and memory abilities.
PMID- 27491494
TI - Redox-Dependent Transformation of a Hydrazinobuckybowl between Curved and Planar
Geometries.
AB - A red-fluorescent heterobuckybowl with an embedded hydrazine structure was
synthesized from a cyclobiphenothiazine derivative via a strained
cyclobicarbazole. The hydrazinobuckybowl was found to possess bowl and twist
structures in the neutral state, a shallow bowl structure in the monocation
state, and a planar structure in the dication state by means of X-ray
crystallographic analysis, DFT calculations, and a comparison of experimental and
calculated (13) C NMR chemical shifts. The hydrazinobuckybowl is the first
buckybowl that changes its geometry between curved bowl/twist structures and a
planar structure depending on the oxidation state. The drastic geometrical change
was possible as a result of the presence of two heteroatoms in the bowl skeleton
and the multiple reversible redox reactions of the compound. Owing to the two
kinds of bowl and twist conformations, the bowl-inversion dynamics of the
hydrazinobuckybowl were found to follow a triple-well potential model.
PMID- 27491493
TI - Alcohol consumption, smoking, and drug use in pregnancy: Prevalence and risk
factors in Southern Thailand.
AB - INTRODUCTION: Substance use during pregnancy contributes to the risk of adverse
health outcomes in mothers and children-in utero and during later development. In
this study, we investigated the prevalence of substance use and associated
factors in pregnant women receiving antenatal care in public hospitals in
Thailand. METHODS: Women (3578) attending 7 antenatal care clinics in Songkhla
for the first time during their current pregnancy were interviewed with a
structured questionnaire focusing on demographic data, obstetric history, use of
alcohol, tobacco, and other substances, and the General Health Questionnaire was
administered. The use of substances was confirmed with the ultrarapid version of
the Alcohol, Smoking, and Substance Involvement Screening Test and urine tests,
which were also administered to 1 in 5 to 10 randomly selected women whose
screening results were negative. RESULTS: Based on self-reports and General
Health Questionnaire results, the weighted prevalence of alcohol, tobacco, or
illicit substance use and that of "mental health problems" were 5.6% (95%
confidence interval [CI], 4.9-6.4) and 29.2% (95% CI, 27.5-30.9), respectively.
On the basis of the ultrarapid version of the Alcohol, Smoking, and Substance
Involvement Screening Test and urine tests, the prevalence of likely substance
use disorder during the 3 months prior to assessment was 1.2% (95% CI, 0.8-1.5)
and 7.7% (95% CI, 4.6-10.7), respectively. Factors associated with substance use
were religion, unmarried status, unplanned pregnancy, previous abortion, and
current mental health problem. DISCUSSION: Our results emphasize the need for
identification of substance use and mental health problems, with the help of
questionnaires and biological markers, followed by early intervention.
PMID- 27491495
TI - MYB expression: Potential role in separating adenoid cystic carcinoma (ACC) from
pleomorphic adenoma (PA).
AB - BACKGROUND: Basaloid tumors of the salivary gland both benign and malignant
comprise ACC, cellular PA, basal cell adenoma (BCA), and basal cell
adenocarcinoma. Rendering a diagnosis given a limited biopsy or fine needle
aspiration (FNA) sample proves challenging. Activation of MYB by gene fusion has
been found in salivary gland ACCs; therefore we investigated the utility of MYB
immunohistochemistry (IHC) as a tool for distinguishing ACCs from other basaloid
neoplasms. METHODS: We selected 48 cases of ACC (11 FNA blocks [CB]), 37
histologic resections [HR]), 74 PA (36 CB, 38 HR), and 18 BCA (7 CB, 11 HR). FNA
CB showed 82% of ACCs (N = 9 of 11) as positive for MYB nuclear staining whereas
68% of ACCs (N = 25 of 37) were positive in HR. RESULTS: All PA were negative for
MYB nuclear staining in both CB (N = 0 of 36) and HR (N = 0 of 38). CB showed 29%
of BCA (N = 2 of 7) as positive for MYB nuclear staining and 55% (N = 6 of 11)
positive in HR. Both ACC and BCA showed significantly higher mean staining
intensity than PA in both CB and HR (P < 0.0001). When comparing ACC and BCA,
significantly higher mean staining intensity was observed in CB (P = 0.02382) but
not in HR (P = 0.42952). CONCLUSION: MYB nuclear staining may prove useful in
separating ACC from PA and BCA, especially in limited cellular samples. Diagn.
Cytopathol. 2016;44:799-804. (c) 2016 Wiley Periodicals, Inc.
PMID- 27491496
TI - Metastatic Malignant Melanoma of the Urinary Bladder in a Patient With Benign
Prostatic Hyperplasia and Urethral Stricture.
PMID- 27491497
TI - New treatment approaches in CLL: Challenges and opportunities in the elderly.
AB - The majority of patients with chronic lymphocytic leukemia (CLL) are over 70years
old. These patients vary in their vulnerability toward treatment efforts.
Heterogeneity in fitness of older patients with CLL is mainly determined by
individual differences in physiological aging and pathological conditions such as
comorbidities and geriatric syndromes. Various options exist to treat older
patients with CLL outside and inside clinical trials. Among these are new
treatment approaches, including chemoimmunotherapy with engineered CD20
antibodies (e.g., obinutuzumab), single agent therapy with kinase inhibitors
(e.g., ibrutinib, idelalisib), other targeted drug therapy (e.g., venetoclax,
lenalidomide), and combinations of these novel compounds. Treatment
recommendations for older patients take patient-related as well as disease
related risk factors into consideration. Emerging new treatment approaches in
older patients offer novel opportunities, but also novel challenges which are
discussed in this review.
PMID- 27491498
TI - Weekly vinorelbine and paclitaxel in older patients with advanced non-small cell
lung cancer: A phase II Fred and Pamela Buffet Cancer Center Clinical Trials
Network study.
AB - OBJECTIVE: Platinum-based doublet chemotherapy is the standard for most patients
with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit
chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective
as single agents in advanced NSCLC. This phase II study evaluates safety and
efficacy of a combination of these two agents in patients >70years with advanced
NSCLC. MATERIALS AND METHODS: Patients with treatment naive metastatic NSCLC
received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with
restaging scans at week 8. Patients with radiographic progression came off study.
The estimated sample size was 29. Toxicity analyses were conducted after 10
patients and again after 19 patients were enrolled. Outcomes were safety and
efficacy, progression free (PFS) and overall survival (OS) and quality of life
(QOL). RESULTS: The study closed at second interim analysis as 6/19 patients had
>=grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemic
encephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever,
death). Of the 16 evaluable patients, 7 completed the study. Disease control rate
(partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No
complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS
7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week
9, but increased at week 17. CONCLUSIONS: Although the combination met its
response end points, increased toxicity makes this combination unsuitable for
older patients. While QOL improved over the study, the small sample hinders
interpretation.
PMID- 27491499
TI - Renal assessment using CKD-EPI equation is useful as an early predictor of
contrast- induced nephropathy in elderly patients with cancer.
AB - OBJECTIVES: To assess respective roles of serum creatinine (SCr) alone and
estimated glomerular filtration rate (eGFR) as an early predictor for contrast
induced nephropathy (CIN) in elderly patients with cancer. MATERIALS AND METHODS:
eGFR of 348 patients at 65years or older with malignancy who underwent contrast
enhanced computed tomography (CECT) were calculated. eGFR was calculated based on
the following three equations: Chronic Kidney Disease Epidemiology Collaboration
equation (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); Cockcroft
Gault (CG). CIN was subdivided into two groups: CIN25% (SCr increase >25% but
<=0.5mg/dl), and CIN0.5 (SCr increase >0.5mg/dl). The occurrence and clinical
outcomes of CIN were determined according to SCr and eGFR. RESULTS: After CECT,
CIN occurred in 50 (14.4%) patients, including 33 CIN25% patients and 17 CIN0.5
patients. CIN0.5 was significantly correlated with prolonged hospitalizations and
increased in-hospital mortality, but not CIN25%. Despite SCr<1.5mg/dl,
preexisting renal insufficiency (RI) was observed in 47 (13.5%) patients based on
CKD-EPI equation, 50 (14.4%) patients based on MDRD equation, and 144 (41.4%)
patients based on CG formula. In preexisting RI, the prevalence of CIN0.5 had an
odds ratio of 15.02 (5.24 to 43.07) based on CKD-EPI equation, 13.73 (4.81 to
39.20) based on MDRD equation, and 5.03 (1.60 to 15.75) based on CG formula.
CONCLUSION: In elderly patients with cancer who visit the emergency department,
renal assessment before CECT using CKD-EPI equation was superior to SCr alone,
MDRD equation, or CG formula in predicting the occurrence of CIN related CECT.
PMID- 27491500
TI - The geriatrician's perspective on practical aspects of the multidisciplinary care
of older adults with cancer.
AB - Multidisciplinary teams (MDTs) have been incorporated into the practical care of
elderly patients with cancer. Several geriatric oncology centres have attempted
to determine the best way to implement MDTs by using geriatric assessment (GA).
Developing a geriatric oncology service is a feasible work, which requires
significant resources. The challenges of MDTs must be known so that better care
planning for elderly patients with cancer can be devised. The aim of this paper
is to discuss the practical aspects of the multidisciplinary care of older adults
with cancer by considering a geriatric point of view and the recent literature.
Reviewing data from recent studies helps enumerate the major challenges in
establishing collaboration in geriatric oncology: evaluating the resources of
your centre, knowing the role of each member of the team, establishing good
communication both within the team and with the patients, and determining
referral criteria and using screening tests to select which patients can benefit
the most from the multidisciplinary evaluation and a more thorough GA.
PMID- 27491501
TI - Remembrance of Professor Steven Wechsler (1948-2016).
PMID- 27491502
TI - Cellular internalization and morphological analysis after intravenous injection
of a highly hydrophilic octahedral rhenium cluster complex - a new promising X
ray contrast agent.
AB - The octahedral cluster compound Na2 H8 [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6
] has been shown to be highly radio dense, thus becoming a promising X-ray
contrast agent. It was also shown that this compound had low cytotoxic effect in
vitro, low acute toxicity in vivo and was eliminated rapidly from the body
through the urinary tract. The present contribution describes a more detailed
cellular internalization assay and morphological analysis after intravenous
injection of this hexarhenium cluster compound at different doses. The median
lethal dose (LD50 ) of intravenously administrated compound was calculated (4.67
+/- 0.69 g/kg). Results of the study clearly indicated that the cluster complex
Hn [{Re6 Se8 }(P(C2 H4 CONH2 )(C2 H4 COO)2 )6 ]n-10 was not internalized into
cells in vitro and induced only moderate morphological alterations of kidneys at
high doses without any changes in morphology of liver, spleen, duodenum, or heart
of mice. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27491503
TI - Macrophage Phenotype in Liver Injury and Repair.
AB - Macrophages hold a critical position in the pathogenesis of liver injury and
repair, in which their infiltrations is regarded as a main feature for both acute
and chronic liver diseases. It is noted that, based on the distinct phenotypes
and origins, hepatic macrophages are capable of clearing pathogens, promoting/or
inhibiting liver inflammation, while regulating liver fibrosis and fibrolysis
through interplaying with hepatocytes and hepatic stellate cells (HSC) via
releasing different types of pro- or anti-inflammatory cytokines and growth
factors. Macrophages are typically categorized into M1 or M2 phenotypes by
adapting to local microenvironment during the progression of liver injury. In
most occasions, M1 macrophages play a pro-inflammatory role in liver injury,
while M2 macrophages exert an anti-inflammatory or pro-fibrotic role during liver
repair and fibrosis. In this review, we focused on the up-to-date information
about the phenotypic and functional plasticity of the macrophages and discussed
the detailed mechanisms through which the phenotypes and functions of macrophages
are regulated in different stages of liver injury and repair. Moreover, their
roles in determining the fate of liver diseases were also summarized. Finally,
the macrophage-targeted therapies against liver diseases were also be evaluated.
PMID- 27491504
TI - Ruthenium-Catalyzed Methylation of Amines with Paraformaldehyde in Water under
Mild Conditions.
AB - Methylated amines are highly important for a variety of pharmaceutical and
agrochemical applications. Existing routes for their formation result in the
production of large amounts of waste or require high reaction temperatures, both
of which impact the ecological and economical footprint of the methodologies.
Herein, we report the ruthenium-catalyzed reductive methylation of a range of
aliphatic amines, using paraformaldehyde as both substrate and hydrogen source,
in combination with water. This reaction proceeds under mild aqueous reaction
conditions. Additionally the use of a secondary phase for catalyst retention and
recycling has been investigated with promising results.
PMID- 27491505
TI - What are the most common first-trimester ultrasound findings in cases of Turner
syndrome?
AB - OBJECTIVES: To identify the most common first-trimester ultrasound findings in
Turner syndrome (TS). To evaluate which first-trimester findings can be best used
to predict the likelihood of TS. METHODS: This was a prospective study, based on
singleton pregnancies. The referrals included 6210 patients. Scan protocol
covered a review of the early fetal anatomy and markers of aneuploidy. RESULTS:
Study population comprised 5644 pregnancies: 5613 with a normal karyotype and 31
cases of TS. Statistically significant differences (p < 0.05) were found between
euploidy and TS groups in terms of nuchal translucency (NT; 1.7 mm versus 8.8 mm)
and fetal heart rate (FHR; 160 versus 171 beats per minute). None of the TS cases
demonstrated absent markers of aneuploidy as opposed to 5133 (91.4%) cases of
euploidy. NT and abnormal DV flow (aDV or revDV) were the most common markers
found in combination in TS cases (n = 17; 54.8%). 27 (0.5%) cases of euploidy and
17 (54.8%) cases of TS revealed congenital heart defects. Fetal hydrops was
observed in 14 cases of TS (43.8%) and in 5 of euploidy (0.1%). In backward
regression model, NT > 3.5 mm and right dominant heart (RDH) augmented the risk
of TS risk by 991 and 314 times, respectively. CONCLUSIONS: First-trimester
sonography is a feasible method to identify the most characteristic features of
TS fenotype. When the first-trimester pattern of TS is considered, a highly
thickened NT, FHR above the 95th percentile, abnormal ductus venosus velocimetry,
fetal hydrops, and RDH should be specifically searched for.
PMID- 27491506
TI - An assessment of lactobiopolymer-montmorillonite composites for dip coating
applications on fresh strawberries.
AB - BACKGROUND: The use of biopolymer coatings appears as a good alternative to
preserve highly perishable fruits, as well as the environment. Proteins generally
produce films with good mechanical properties, although their highly hydrophilic
nature limits the use in many applications. Nanoparticles, such as nanoclays, can
play a critical role in improving barrier properties. The present study evaluated
the effect of the addition of montmorillonite (MMT)-nanoparticles to a lacto
biopolymer coating, focusing on: (i) the morphological, thermal and barrier
properties of the material and (ii) the shelf life of coated fresh strawberries.
RESULTS: The addition of MMT improved the water vapor barrier property.
Morphological and thermal analysis indicated a good interaction between the milk
protein and the nanoclay, which was intercalated within the milk protein base
(MPB) matrix, offering a more tortuous path to diffusing migrants. The MMT-MPB
coating helped to significantly (P <= 0.05) reduce the weight loss, as well as
oxygen uptake and the release of carbon dioxide, and improved the fruit firmness
and reduced mould and yeast load compared to the uncoated fruits. The addition of
MMT gave statistical difference (P <= 0.05) in terms of weight loss, subjective
global appearance and purchase intention of coated fresh strawberries.
CONCLUSION: The addition of nanofillers, such as MMT, into protein-based coating
could improve its water vapour barrier and could affect, positively, some
parameters of the shelf life of coated strawberries. (c) 2016 Society of Chemical
Industry.
PMID- 27491507
TI - Tuning the emission properties of a fluorescent polymer using a polymer
microarray approach - identification of an optothermo responsive polymer.
AB - Polymer microarrays were prepared using inkjet printing mixtures of acrylate
monomers each with a common fluorescent fluorene co-polymer. Fluorescence
analysis of each of the features on the array allowed identification of polymers
that could tune the fluorescence under a variety of insults. The "hit" polymers
were made into beads via reverse suspension polymerization and their fluorescence
properties were analyzed.
PMID- 27491508
TI - Peptides@mica: from affinity to adhesion mechanism.
AB - Investigating the adsorption of peptides on inorganic surfaces, on the molecular
level, is fundamental for medicinal and analytical applications. Peptides can be
potent as linkers between surfaces and living cells in biochips or in
implantation medicine. Here, we studied the adsorption process of the positively
charged pentapeptide RTHRK, a recently identified binding sequence for surface
oxidized silicon, and novel analogues thereof to negatively charged mica
surfaces. Homogeneous formation of monolayers in the nano- and low micromolar
peptide concentration range was observed. We propose an alternative and efficient
method to both quantify binding affinity and follow adhesion behavior. This
method makes use of the thermodynamic relationship between surface coverage,
measured by atomic force microscopy (AFM), and the concomitant free energy of
adhesion. A knowledge-based fit to the autocorrelation of the AFM images was used
to correct for a biased surface coverage introduced by the finite lateral
resolution of the AFM. Binding affinities and mechanisms were further explored by
large scale molecular dynamics (MD) simulations. The combination of well
validated MD simulations with topological data from AFM revealed a better
understanding of peptide adsorption processes on the atomistic scale. We
demonstrate that binding affinity is strongly determined by a peptide's ability
to form salt bridges and hydrogen bonds with the surface lattice. Consequently,
differences in hydrogen bond formation lead to substantial differences in binding
affinity despite conservation of the peptide's overall charge. Further, MD
simulations give access to relative changes in binding energy of peptide
variations in comparison to a lead compound.
PMID- 27491509
TI - Multidisciplinary Treatment of Severe Upper Incisor Root Resorption Secondary to
Transposed Canine.
AB - OBJECTIVE: Tooth transposition is a rare dental anomaly that could lead to
undesirable side effects on other teeth. This case report aims to describe the
multidisciplinary treatment of a patient with a severely resorbed permanent
maxillary central incisor due to transposition with the permanent canine.
CLINICAL CONSIDERATIONS: A girl aged 13 years and 7 months with a chief complaint
of a pink spot on her maxillary left incisor with a slightly erupted tooth above
it was referred to our clinic. Her left maxillary canine was transposed to her
left central incisor site. The left canine was impacted and had caused severe
resorption of the left central incisor root. Her maxillary left canine was
substituted for the central incisor after the compulsory extraction of her left
central incisor. The canine was prosthetically restored after orthodontic
treatment. The results were stable 1 year after treatment had been completed.
CONCLUSIONS: Orthodontic treatment in coordination with other dental specialties
like prosthodontics, periodontology and oral and maxillofacial surgery can
provide functional and esthetic outcome in cases of severely transposed canines.
CLINICAL SIGNIFICANCE: This is a rare case of transposition that shows the
significant root resorption on the maxillary central incisor due to the ectopic
eruption of the canine. Canine substitution for the central incisor was chosen as
a treatment plan instead of placing an implant. An esthetic smile and a
functional occlusion were established at the end of the treatment. (J Esthet
Restor Dent 29:5-12, 2017).
PMID- 27491510
TI - A visible light-driven photocatalyst of a stable metal-organic framework based on
Cu4Cl clusters and TIPE spacers.
AB - A 3D new metal-organic framework (MOF) [Cu4Cl(TIPE)3].3Cl (1) has been
synthesized and characterized. Compound 1 exhibits good chemical stability in
aqueous solution with the pH ranging from 1 to 11. Interestingly, compound 1
shows high catalytic activities for the degradation of dyes (RhB, MB and MO)
under LED and natural light irradiation. The Ea of 1 for RhB, MB and MO
degradation is obtained to be 79.71, 66.14 and 87.26 kJ mol(-1), respectively.
Furthermore, compound 1 can be reused in the catalytic process without the
catalytic activity obviously decreasing.
PMID- 27491511
TI - Work-related Injuries Among Emergency Medical Technicians in Western Turkey.
AB - OBJECTIVES: Emergency medical technicians (EMTs) and paramedics are at serious
risk for work-related injuries (WRIs) during work hours. Both EMTs and paramedics
have higher WRI rates, according to the literature data. This study was designed
to investigate causes and characteristics of WRIs involving EMTs and paramedics
staffed in Western Turkey. METHODS: All health care personnel staffed in
Emergency Medical Services (EMS) in the city were interviewed face-to-face in
their off-duty hours to inform them about the study. Excluded from the study were
those who declined to participate in the study, those who were not on duty during
the two-month study period, and those who had been working in the EMS for less
than one year. The subjects were asked to answer multiple-choice questions.
RESULTS: A total of 163 personnel (117 EMTs and 46 paramedics) comprised the
study sample. Eighty-three personnel (50.9%) were female and mean age was 29.7
years (SD=8.4 years). The most common mechanisms of WRI, as reported by the
personnel, were motor vehicle accidents (MVAs; 31.9%), needlestick injuries
(16.0%), ocular exposure to bodily fluids (15.4%), and sharp injuries (9.8%),
respectively. Needlestick injuries commonly occurred during intravenous line
procedures (59.4%) and inside the cruising ambulance (n=20; 62.5%). Working
inside the cruising ambulance was the most commonly accused cause of the WRI
(41.3%). CONCLUSION: Paramedic personnel and EMTs are under high risk of WRI.
Motor vehicle accidents and needlestick injuries were the most common causes of
WRI. Strict measures need to be taken to restructure the interior design to
protect personnel from all kinds of WRIs. Yilmaz A , Serinken M , Dal O , Yaylaci
S , Karcioglu O . Work-related injuries among emergency medical technicians in
Western Turkey. Prehosp Disaster Med. 2016;31(5):505-508.
PMID- 27491512
TI - Multimodal imaging of foveal cavitation in retinal dystrophies.
AB - PURPOSE: Inherited retinal dystrophies and cone dysfunction syndromes may show a
sharp hyporeflective interruption in the outermost retinal layers on optical
coherence tomography (OCT), known as foveal cavitation (FC). The aim of the study
was to describe the morpho-functional features of FC in patients affected by
retinal dystrophies by means of multimodal imaging. METHODS: A consecutive series
of patients affected by FC were prospectively recruited for the study. Patients
underwent short-wavelength (SW) and near-infraRed (NIR) fundus autofluorescence
(FAF), spectral domain OCT (SD-OCT), microperimetry (MP), and multifocal
electroretinogram (mfERG). Mean size of FC on OCT was correlated with best
corrected visual acuity (BCVA). RESULTS: Overall, 15 patients (30 eyes) were
enrolled. Mean age was 38.2 +/- 14.5 years (range: 10-60), with nine females (60
%). Mean BCVA was 0.5 +/- 0.4 LogMAR. SD-OCT revealed focal loss of outer retinal
layers and disruption of inner segment ellipsoid zone. Vertical height of FC
(mean 27.77 +/- 18.77 MUm) was indirectly related to BCVA; complete forms of FC,
with total loss of outer OCT bands, showed a poorer visual outcome. The FC size
on NIR-FAF turned out to be larger with respect to SD-OCT and SW-FAF. CONCLUSION:
Our data indicate that the presence of FC worsens functional outcome in patients
affected by retinal disorders; complete and higher lesions are associated with a
worse morpho-functional prognosis in these eyes.
PMID- 27491513
TI - A review on prolificacy genes in sheep.
AB - Ovulation rate and litter size are important reproduction traits in sheep and are
of high economic value. Reproduction traits typically have low to medium
heritabilities and do not exhibit a noticeable response to phenotypic selection.
Therefore, inclusion of genetic information of the genes associated with
reproductive ability could efficiently enhance the selection response. The most
important major genes affecting prolificacy and their genetic diversities in
different sheep breeds were reviewed. Different causative mutations with major
effects on reproductive traits including ovulation rate and litter size have been
found in various sheep breeds around the world. A general overview of the studies
on main prolificacy genes showed that some alleles may express different
phenotypic effects in different breeds, and thus, further studies on epistatic
effects are necessary for more understanding of genetic control of reproductivity
in sheep. Regarding the polygenic control of fertility traits, application of new
high-throughput technologies to find new variants is essential for future
studies. Moreover, genomewide association studies and genomic best linear
unbiased predictions of breeding values are likely to be effective tools for
genetic improvement of sheep reproductive performance traits.
PMID- 27491514
TI - Aqueous photocatalytic degradation of selected micropollutants by Pd-modified
titanium dioxide in three photoreactor types.
AB - The goals of the present study were to synthesise highly efficient Pd-TiO2
photocatalyst, to characterise its performance in slurry in smaller scale and to
investigate its performance in the aqueous photocatalytic oxidation of three
antibiotics: doxycycline, sulphamethizole and amoxicillin. The performance of the
photocatalyst was evaluated in an open batch slurry reactor equipped with a
fluorescent long-wavelength ultraviolet (UVA) lamp (0.2 L). With the fastest
degrading doxycycline, experimental research was continued in a fixed-bed
continuous flow photoreactor (0.13 L), with the Pd-TiO2 photocatalyst attached to
a glass plate, and a medium laboratory-scale three-phase fluidised-bed reactor (2
L) equipped with four fluorescent UVA lamps, with the photocatalyst attached to
the surface of expanded clay granules employed as the bed material. While showing
very high activity in the batch slurry reactor, far surpassing P25 Aeroxide, the
performance of Pd-TiO2 with doxycycline was comparable to P25 in the semi
continuous reactors.
PMID- 27491515
TI - Single-electron induced surface plasmons on a topological nanoparticle.
AB - It is rarely the case that a single electron affects the behaviour of several
hundred thousands of atoms. Here we demonstrate a phenomenon where this happens.
The key role is played by topological insulators-materials that have surface
states protected by time-reversal symmetry. Such states are delocalized over the
surface and are immune to its imperfections in contrast to ordinary insulators.
For topological insulators, the effects of these surface states will be more
strongly pronounced in the case of nanoparticles. Here we show that under the
influence of light a single electron in a topologically protected surface state
creates a surface charge density similar to a plasmon in a metallic nanoparticle.
Such an electron can act as a screening layer, which suppresses absorption inside
the particle. In addition, it can couple phonons and light, giving rise to a
previously unreported topological particle polariton mode. These effects may be
useful in the areas of plasmonics, cavity electrodynamics and quantum
information.
PMID- 27491517
TI - Vision in Plants via Plant-Specific Ocelli?
AB - Although plants are sessile organisms, almost all of their organs move in space
and thus require plant-specific senses to find their proper place with respect to
their neighbours. Here we discuss recent studies suggesting that plants are able
to sense shapes and colours via plant-specific ocelli.
PMID- 27491516
TI - The Unexpected Diversity of Plant Organelle RNA Editosomes.
AB - Flowering plants convert many hundreds of organelle cytidines (Cs) to uridines
(Us) during post-transcriptional RNA editing. Pentatricopeptide repeat (PPR)
proteins dictate specificity by recognizing RNA sequences near C targets.
However, the complete mechanism of the editing machinery is not yet understood.
Recently, non-PPR editing factors [RNA editing factor interacting proteins
(RIPs)/multiple organellar RNA editing factors (MORFs), organelle RNA recognition
motif (ORRM) proteins, organelle zinc-finger (OZ) proteins, and
protoporphyrinogen oxidase 1 (PPO1)] have been identified as components of the
plant RNA editosome, which is a small RNA-protein complex. Surprisingly, plant
editosomes are highly diverse not only with regard to the PPR proteins they
contain but also in the non-PPR components that are present. Here we review the
most recent progress in the field and discuss the implications of the diversity
of plant editosomes for the evolution of RNA editing and for possible future
applications.
PMID- 27491518
TI - Investigating the effect of landfill leachates on the characteristics of
dissolved organic matter in groundwater using excitation-emission matrix
fluorescence spectra coupled with fluorescence regional integration and self
organizing map.
AB - For the purpose of investigating the effect of landfill leachate on the
characteristics of organic matter in groundwater, groundwater samples were
collected near and in a landfill site, and dissolved organic matter (DOM) was
extracted from the groundwater samples and characterized by excitation-emission
matrix (EEM) fluorescence spectra combined with fluorescence regional integration
(FRI) and self-organizing map (SOM). The results showed that the groundwater DOM
comprised humic-, fulvic-, and protein-like substances. The concentration of
humic-like matter showed no obvious variation for all groundwater except the
sample collected in the landfill site. Fulvic-like substance content decreased
when the groundwater was polluted by landfill leachates. There were two kinds of
protein-like matter in the groundwater. One kind was bound to humic-like
substances, and its content did not change along with groundwater pollution.
However, the other kind was present as "free" molecules or else bound in
proteins, and its concentration increased significantly when the groundwater was
polluted by landfill leachates. The FRI and SOM methods both can characterize the
composition and evolution of DOM in the groundwater. However, the SOM analysis
can identify whether protein-like moieties was bound to humic-like matter.
PMID- 27491519
TI - Outcomes of Sacral Neuromodulation in a Privately Insured Population.
AB - OBJECTIVE: In this study, we analyzed claims data from the Ingenix data base to
analyze outcomes of sacral neuromodulation with respect to both provider and
patient factors. MATERIALS AND METHODS: We used the Ingenix (I3) data base to
determine demographic, diagnosis, and procedure success information for years
2002-2007 for privately insured patients. Demographic information was obtained,
as were the diagnoses given and procedures performed, based on ICD-9 diagnosis
codes and Current Procedural Terminology procedure codes. Multivariate analysis
was performed to identify specific predictors of success, as measured by
progression to implantation of a pulse generator. RESULTS: Overall success, as
defined by battery placement, was 49.1%. Fifty-one percent of staged procedures
were followed by battery placement compared with 24.1% of percutaneous cases (p <
0.0001). Among the patient variables analyzed, women were more likely than men to
progress to battery placement. After Stage I testing, patients treated by
urologists were overall more likely than gynecologists to proceed to battery
placement (I3: 54% vs. 47%, p < 0.0001). Unlike previous findings in other claims
based data sets, we did not observe a provider-volume relationship in the i3 data
set. CONCLUSIONS: Success of sacral neuromodulation, as defined by proceeding to
battery placement, was much better after formal staged procedures, which leads us
to question the utility of percutaneous techniques. Outcomes were also better
among female patients and among those treated by a urologist. Specialty
differences will likely diminish over time as more gynecologists adopt sacral
neuromodulation.
PMID- 27491520
TI - Non-Covalently Stabilized Alginate Hydrogels as Functional Cell Scaffold
Material.
AB - Biopolymers are an attractive class of compounds for being used in biomedical
applications as they are widely available from biomass. Their drawback is the
lack of mechanical stability and the ability to tune this properly. Covalent
chemical cross-linking is an often used approach but it limits usability due to
legislation as well as the need of advanced and specialized knowledge by end
users such as clinicians. Here, increased and tunable mechanical properties are
achieved of alginate-based hydrogels with non-covalent approaches using linear
polyethyleneimine (LPEI) as a polyelectrolyte rather than only multivalent metal
ions (Ca2+ ). Gel stiffness increases with increasing LPEI content. Gel
morphology changes from a thin fibrous mesh for alginate-Ca2+ to thicker fibrous
networks when LPEI is introduced. The gels are able to efficiently release
encapsulated small molecular dyes and the gels are able to host cells. For the
cell encapsulation human skin fibroblasts (HSkF) and human bone marrow-derived
mesenchymal stem cells (hBM-MSC) are used. HSkF can be successfully incorporated
without diminished viability while the matrix components and gel preparation
method are not compatible with hBM-MSC. The newly developed alginate-based system
is regarded as a potential candidate for wound dressing materials.
PMID- 27491521
TI - Proteomic analysis of FFPE tissue: barriers to clinical impact.
PMID- 27491522
TI - HEALTH TECHNOLOGY ASSESSMENTS REPORTING COST-EFFECTIVENESS OF TRANSCATHETER
AORTIC VALVE IMPLANTATION.
AB - OBJECTIVES: Made available since 2002, transcatheter aortic valve implantation
(TAVI) is a minimally invasive new intervention which can provide significant
survival improvement to patients with aortic stenosis. However, TAVI is expensive
and currently not reimbursed by many governments. Some governments and
institutions have been conducting health technology assessments (HTAs) to inform
their reimbursement decisions. The aim of the present study is to review HTAs
that have relied on a cost-effectiveness analysis to inform reimbursement
decisions of TAVI. METHODS: A systematic literature review was conducted among
published literature as well as reports released by HTA agencies. Predetermined
inclusion and exclusion criteria, following the Preferred Reporting System for
Systematic Reviews and Meta-Analysis guidelines, were used to select relevant
HTAs. The selected papers were assessed against the Consolidated Health Economic
Evaluation Reporting Standards. RESULTS: HTAs on TAVI from three countries were
available for this review: Canada, Belgium, and the United Kingdom. All three
HTAs used the Placement of Aortic Transcatheter Valve (PARTNER) trial data with
Markov models to estimate the incremental cost effectiveness ratio. The three
HTAs recommended conditional reimbursement for TAVI for otherwise inoperable
patients. The HTAs did not use clear methods to estimate the health-related
utility which ultimately affected their cost-effectiveness results. The UK HTA
showed the best value for money (US$20,416 per quality-adjusted life-year).
CONCLUSION: All studies found TAVI to be more costly and less effective for high
risk patients suitable for surgery, whereas TAVI was consistently found to be
cost effective for otherwise inoperable patients.
PMID- 27491523
TI - Obituary: a tribute to Yoshihiro Kaneko, MD.
PMID- 27491524
TI - Erratum: Increased neutrophil to lymphocyte ratio in persons suffering from
hypertension with hyperhomocysteinemia.
PMID- 27491525
TI - QQ-plots for assessing distributions of biomarker measurements and generating
defensible summary statistics.
AB - One of the main uses of biomarker measurements is to compare different
populations to each other and to assess risk in comparison to established
parameters. This is most often done using summary statistics such as central
tendency, variance components, confidence intervals, exceedance levels and
percentiles. Such comparisons are only valid if the underlying assumptions of
distribution are correct. This article discusses methodology for interpreting and
evaluating data distributions using quartile-quartile plots (QQ-plots) and making
decisions as to how to treat outliers, interpreting effects of mixed
distributions, and identifying left-censored data. The QQ-plot graph is shown to
be a simple and elegant tool for visual inspection of complex data and deciding
if summary statistics should be performed after log-transformation.
PMID- 27491526
TI - Screening Caregivers of Children for Risky Drinking in KwaZulu-Natal, South
Africa.
AB - Background and Objectives Alcohol abuse, a significant health problem in South
Africa, affects the ability of adults to care for children. Little is known
regarding risky alcohol use among child caregivers there. A large population
based study examined the prevalence of, and factors associated with, risky
drinking among caregivers of young children in KwaZulu-Natal, South Africa
comparing the use of the Alcohol Use Disorders Identification Test (AUDIT) and
the AUDIT-C screens for hazardous or harmful drinking (referred to here as risky
drinking). Methods 83 % of child caregivers from five tribal areas were
interviewed using the 10-question AUDIT to screen for risky drinking. The AUDIT-C
screen, a subset of AUDIT questions, targets alcohol consumption and binge
drinking. Factors associated with risky drinking were investigated using logistic
regression. Results 1434 caregivers participated, 98 % female. Sixteen percent
reported ever drinking alcohol. Based on AUDIT criteria for risky drinking, 13 %
of the sample scored as moderate drinkers, 2 % as hazardous users, and 1 % as
harmful or dependent users (identifying 3 % as risky drinkers). Using AUDIT-C
criteria to identify risky drinking significantly increased the proportion of
caregivers identified as risky drinkers to 9 %. In multivariate analyses, factors
associated with risky drinking were similar in both screens: partner violence,
smoking, HIV-infection, caring for a child with disabilities. Conclusions for
Practice Since the AUDIT-C identified risky alcohol use not otherwise detected
with the full AUDIT, and since resources for screening in health care settings is
limited, the AUDIT-C may be a more appropriate screen in populations where binge
drinking is common.
PMID- 27491527
TI - Unintended Childbearing and Child Growth in Northern Malawi.
AB - Objective The study aims to assess whether unintended children experience slower
growth than intended children. Methods We analysed longitudinal data linked to
the Karonga Health and Demographic Surveillance Site collected over three rounds
between 2008 and 2011 on women's fertility intentions and anthropometric data of
children. Using the prospective information on fertility intention we assessed
whether unintended children are more likely to be stunted than intended children.
We applied Propensity Score Matching technique to control for endogenous factors
affecting both the probability that a family has an unwanted birth and a child
with poor health outcomes. Results We found that 24 % of children from unwanted
pregnancies were stunted compared with 18 % of mistimed pregnancies and 17 % of
those from wanted pregnancies. However, these differences in probability of
children being stunted, though in the expected direction, were not significant
either for large or small families, after controlling for age. The number of
children in the household was associated with stunting and boys were
substantially more likely to be stunted than girls. Conclusion We found no
significance difference in probability of being stunted by mother's fertility
intention.
PMID- 27491528
TI - Medicare Competitive Bidding Program.
AB - A recent study by the National Minority Quality Forum (NMQF) reported the
failures and adverse health outcomes of the Medicare competitive bidding program
as implemented by the Centers for Medicare & Medicaid Services (CMS) in 2011. CMS
has repeatedly reported that the program caused no disruption of beneficiary
access to needed medical products (including diabetes testing supplies) and that
no adverse outcomes occurred. Although signals of disruption were seen early in
the program implementation, economic modeling by McGeary and Katzman in 2004
demonstrated that the program design was significantly flawed. This article
discusses the unintended consequences of competitive bidding program and provides
a rationale for suspending the program until CMS can implement effective
monitoring protocols to protect the safety of Medicare beneficiaries.
PMID- 27491529
TI - Arm, Leg, and Foot Skin Water in Persons With Diabetes Mellitus (DM) in Relation
to HbA1c Assessed by Tissue Dielectric Constant (TDC) Technology Measured at 300
MHz.
AB - BACKGROUND: DM is associated with structural skin changes. However, few studies
have investigated changes in dermal water and specifically its relationship to
glucose control as measured by HbA1c. Our goal was to test the hypothesis that
skin water, assessed by its tissue dielectric constant (TDC), is inversely
related to HbA1c. METHODS: Water content of 3 skin sites (forearm, lower leg, and
foot dorsum) of 50 persons with DM was estimated by measuring TDC at 300 MHz. TDC
is the ratio of tissue dielectric constant to vacuum and depends on free and
bound water in the measured volume. TDC was measured in triplicate to 4 depths,
0.5. 1.5, 2.5, and 5.0 mm to include different skin components. RESULTS: At each
site increased measurement depth showed (1) a significant decrease in absolute
TDC values and (2) a significant increase in foot-to-arm TDC ratios. TDC values
at forearm were shown to be greater than at either leg or foot. However, testing
of these 50 patients at 3 sites and 4 skin depths did not show any significant
relationship between TDC and HbA1c or fasting glucose. CONCLUSIONS: The data
indicate no relationship between TDC values, as indices for skin water, and HbA1c
or fasting glucose. This implies that skin TDC values to assess skin property
features and changes in persons with DM are not sensitive to recent glucose
control. Furthermore, the results introduce a newly applied TDC technology useful
to assess skin properties of persons with DM.
PMID- 27491530
TI - mHealth Real-Time Blood Glucose Monitoring Facilitates Glycemic Management.
PMID- 27491531
TI - Exposure-based cognitive-behavioural therapy via the internet and as
bibliotherapy for somatic symptom disorder and illness anxiety disorder:
randomised controlled trial.
AB - BACKGROUND: In DSM-5 two new diagnoses, somatic symptom disorder (SSD) and
illness anxiety disorder (IAD), have replaced DSM-IV hypochondriasis. There are
no previous treatment studies for these disorders. Cognitive-behavioural therapy
(CBT) delivered as therapist-guided or unguided internet treatment or as unguided
bibliotherapy could be used to increase treatment accessibility. AIMS: To
investigate the effect of CBT delivered as guided internet treatment (ICBT),
unguided internet treatment (U-ICBT) and as unguided bibliotherapy. METHOD: A
randomised controlled trial (RCT) where participants (n = 132) with a diagnosis
of SSD or IAD were randomised to ICBT, U-ICBT, bibliotherapy or to a control
condition on a waiting list (trial registration: Clinicaltrials.gov identifier
NCT01966705). RESULTS: Compared with the control condition, all three treatment
groups made large and significant improvements on the primary outcome Health
Anxiety Inventory (between-group d at post-treatment was 0.80-1.27). CONCLUSIONS:
ICBT, U-ICBT and bibliotherapy can be highly effective in the treatment of SSD
and IAD. This is the first study showing that these new DSM-5 disorders can be
effectively treated.
PMID- 27491533
TI - Effectiveness of trauma-focused treatment for patients with psychosis with and
without the dissociative subtype of post-traumatic stress disorder.
AB - This study presents secondary analyses of a recently published trial in which
post-traumatic stress disorder (PTSD) patients with psychosis (n = 108) underwent
8 sessions of trauma-focused treatment, either prolonged exposure (PE) or eye
movement desensitisation and reprocessing (EMDR) therapy. 24.1% fulfilled the
criteria for the dissociative subtype, a newly introduced PTSD subtype in DSM-5.
Treatment outcome was compared for patients with and without the dissociative
subtype of PTSD. Patients with the dissociative subtype of PTSD showed large
reductions in clinician-administered PTSD scale (CAPS) score, comparable with
patients without the dissociative subtype of PTSD. It is concluded that even in a
population with severe mental illness, patients with the dissociative subtype of
PTSD do benefit from trauma-focused treatments without a pre-phase of emotion
regulation skill training and should not be excluded from these treatments.
PMID- 27491532
TI - Longitudinal course of behavioural and psychological symptoms of dementia:
systematic review.
AB - BACKGROUND: More information about the pattern of behavioural and psychological
symptoms of dementia (BPSD) in the course of dementia is needed to inform
patients and clinicians and to design future interventions. AIMS: To determine
the persistence and incidence of BPSD and their relation to cognitive function,
in individuals with dementia or in cohorts investigated for dementia onset.
METHOD: A systematic literature review analysed the baseline prevalence,
persistence and incidence of 11 symptoms. The review was conducted according to
established guidelines with the exception that we could not exclude the
possibilities of bias in the studies examined. RESULTS: The 59 included studies
showed considerable heterogeneity in their objectives and methods. The symptoms
hyperactivity and apathy showed high persistence and incidence; depression and
anxiety low or moderate persistence and moderate incidence; and psychotic
symptoms low persistence with moderate or low incidence. CONCLUSIONS: Despite
heterogeneity across studies in terms of setting, focus and length of follow-up,
there were clinically relevant differences in the longitudinal courses of
different BPSD. Apathy was the only symptom with high baseline prevalence,
persistence and incidence during the course of dementia.
PMID- 27491534
TI - Association of timing of menarche with depressive symptoms and depression in
adolescence: Mendelian randomisation study.
AB - BACKGROUND: Observational studies report associations between early menarche and
higher levels of depressive symptoms and depression. However, no studies have
investigated whether this association is causal. AIMS: To determine whether
earlier menarche is a causal risk factor for depressive symptoms and depression
in adolescence. METHOD: The associations between a genetic score for age at
menarche and depressive symptoms at 14, 17 and 19 years, and depression at 18
years, were examined using Mendelian randomisation analysis techniques. RESULTS:
Using a genetic risk score to indicate earlier timing of menarche, we found that
early menarche is associated with higher levels of depressive symptoms at 14
years (odds ratio per risk allele 1.02, 95% CI 1.005-1.04, n = 2404). We did not
find an association between the early menarche risk score and depressive symptoms
or depression after age 14. CONCLUSIONS: Our results provide evidence for a
causal effect of age at menarche on depressive symptoms at age 14.
PMID- 27491535
TI - The use of thermographic imaging to evaluate therapeutic response in human tumour
xenograft models.
AB - Non-invasive methods to monitor tumour growth are an important goal in cancer
drug development. Thermographic imaging systems offer potential in this area,
since a change in temperature is known to be induced due to changes within the
tumour microenvironment. This study demonstrates that this imaging modality can
be applied to a broad range of tumour xenografts and also, for the first time,
the methodology's suitability to assess anti-cancer agent efficacy. Mice bearing
subcutaneously implanted H460 lung cancer xenografts were treated with a novel
vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects
on tumour temperature were assessed using thermographic imaging over the first 6
hours post-administration and subsequently a further 7 days. For ICT-2552 a
significant initial temperature drop was observed, whilst for both agents a
significant temperature drop was seen compared to controls over the longer time
period. Thus thermographic imaging can detect functional differences (manifesting
as temperature reductions) in the tumour response to these anti-cancer agents
compared to controls. Importantly, these effects can be detected in the first few
hours following treatment and therefore the tumour is observable non-invasively.
As discussed, this technique will have considerable 3Rs benefits in terms of
reduction and refinement of animal use.
PMID- 27491536
TI - Metabolic activities of five botryticides against Botrytis cinerea examined using
the Biolog FF MicroPlate.
AB - Tobacco grey mold caused by Botrytis cinerea is an important fungal disease
worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are
representative botryticides for grey mold management. This research investigated
the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog
FF Microplate. All five chemicals showed inhibitory activity, with average EC50
values of 0.94, 0.05, 0.50, 0.61 and 0.31 MUg ml(-1), respectively. B. cinerea
metabolized 96.8% of tested carbon sources, including 29 effectively and 33
moderately, but the metabolic fingerprints differed under pressures imposed by
these botryticides. For boscalid, B. cinerea was unable to metabolize many
substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources
related to glycolysis were not metabolized. For iprodione, use of most carbon
substrates was weakly inhibited, and the metabolic profile was similar to that of
the control. For propiconazole, no carbon substrates were metabolized and the
physiological and biochemical functions of the pathogen were totally inhibited.
These findings provide useful information on metabolic activities of these
botryticides, and may lead to future applications of the Biolog FF Microplate for
examining metabolic effects of other fungicides on other fungi, as well as
providing a metabolic fingerprint of B. cinerea that could be useful for
identification.
PMID- 27491538
TI - Does the Use of Intraoperative Microelectrode Recording Influence the Final
Location of Lead Implants in the Ventral Intermediate Nucleus for Deep Brain
Stimulation?
AB - To determine if the use of intraoperative microelectrode recording (MER)
influences the final location of lead implant in deep brain stimulation (DBS) of
the ventral intermediate nucleus (VIM), and to evaluate the incidence of
associated complications. The usefulness of intraoperative MER in DBS is debated,
some centers suggesting it increases complications without additional benefit. We
conducted a retrospective chart review of all patients who underwent VIM DBS with
MER at the University of Texas Health Science Center in Houston from June 1, 2009
to October 1, 2013. Initial (MRI determined) and final (intraoperative MER
determined) coordinates of implant were compared. To assess incidences of
hemorrhagic and infectious complications, we reviewed postoperative CT scans and
follow-up notes. Forty-five lead implants on 24 patients were reviewed. The mean
age at implantation was 62.42 years (range 18-83). The average duration from
diagnosis to surgery was 21.5 years (range 1-52). A statistically significant
mean difference was observed in the superior-inferior plane (0.52 +/- 0.80 mm
inferiorly, p < 0.05) and the anterior-posterior plane (0.45 +/- 0.86 mm
posteriorly, p < 0.05). A non-statistically significant difference was also
observed in the medial-lateral plane (0.02+/- 0.15 mm, p > 0.05). One patient
developed an infectious complication (4.2 %) that required removal of leads; two
patients had minimal asymptomatic intra-ventricular bleeding (8.3 %). In our DBS
center, intraoperative MER in VIM DBS implant does not seem to have a higher rate
of surgical complications compared to historical series not using MER, and might
also be useful in determining the final lead location.
PMID- 27491537
TI - [Social psychiatry and neurobiology : A long overdue convergence exemplified by
schizophrenia].
AB - BACKGROUND: The proliferation of biological psychiatry has greatly increased over
the last two decades. With the possibility to carry out brain research using
modern technical methods, it seemed that social influencing factors would lose
importance in the development of mental diseases; however, in actual fact this
does not seem to be justified. It is necessary to overcome this separation, in
that social factors are incorporated into a conceptual framework in the
development of mental diseases, which simultaneously also takes the results of
current neurobiological research into consideration. OBJECTIVES AND METHODS: The
aims of this review article are to summarize the current state of
sociopsychiatric research and to emphasize the perspectives of the biological
principles and their validity with respect to the social dimensions of
psychiatry, as exemplified by schizophrenic disorders. The article presents the
options for a biosocial approach in social psychiatry and gives an overview of
the currently available literature. RESULTS AND CONCLUSION: There is an abundance
of neurobiological research approaches, which are closely associated with
sociopsychiatric topics, such as social cognition. Social psychiatry and
biological psychiatry should no longer be considered as diametrically opposed
subdisciplines. On the contrary, the options which could emerge from a synthesis
must be used in research and clinical practice.
PMID- 27491539
TI - Minimally invasive direct coronary bypass compared with percutaneous coronary
intervention for left anterior descending artery disease: a meta-analysis.
AB - BACKGROUND: The clinical outcomes for left anterior descending (LAD) coronary
artery lesion between minimally invasive direct coronary artery bypass (MIDCAB)
and percutaneous coronary intervention (PCI) are still controversial. The
objective was to compare safety and efficacy between MIDCAB and PCI for LAD.
METHODS: Electronic databases and article references were systematically searched
to access relevant studies. End points included mortality, myocardial infarction,
target vessel revascularization (TVR), major adverse coronary events (MACE),
angina recurrence, and stroke. RESULTS: Fourteen studies with 941 patients were
finally involved in the present study. The mortality and incidence of myocardial
infarction were similar in MIDCAB and PCI groups at 30 days, 6 months, and at
follow-up beyond 1 year. Compared with PCI, MIDCAB decreased incidence of TVR and
MACE at 6 months and beyond 1 year follow-up. MIDCAB was associated with a lower
incidence of angina recurrence at 6 months compared with PCI. PCI was associated
with higher risk of restenosis in target vessel. No significant difference was
shown for stroke. CONCLUSION: Our meta-analysis indicates that there are no
significant differences in the safety between MIDCAB and PCI in patients with
LAD. However MIDCAB is superior to PCI for TVR and MACE.
PMID- 27491541
TI - Hemodynamic deterioration after aortic valve replacement in a patient with mixed
systemic amyloidosis.
AB - We report a case of hemodynamic deterioration after aortic valve replacement in a
patient with mixed systemic amyloidosis. A 77-year-old male with severe aortic
valve stenosis and 19 years hemodialysis underwent aortic valve replacement.
Postoperatively, the patient died of hemodynamic deterioration. Autopsy findings
showed massive, whole-body edema and mixed systemic amyloidosis (dialysis-related
and AA amyloidosis). Clinical and autopsy findings implied that hemodynamic
deterioration was caused by increased vascular permeability. The amyloid deposit
to the vessel causes inflammatory changes and increases vascular permeability.
Mixed systemic amyloidosis occurs very rarely and could increases vascular
permeability even more than each single type of amyloidosis. Systemic amyloidosis
may be a risk factor for hemodynamic deterioration after cardiac surgery.
Patients with longtime hemodialysis and a history associated with dialysis
related amyloidosis would have at least single systemic amyloidosis, which should
be considered a contraindication to cardiac surgery with cardiopulmonary bypass.
PMID- 27491540
TI - Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its
inhibitor.
AB - BACKGROUND: We comprehensively analyzed X-ray cocrystal structures of dipeptidyl
peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its
general or partial structure according to the inhibitor used and whether DPP-4
has a common rule for inhibitor binding. RESULTS: All the main and side chains in
the inhibitor binding area were minimally altered, except for a few side chains,
despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205,
Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom
of inhibitor to a particular spatial position in DPP-4. We found two specific
water molecules that were common to 92 DPP-4 structures. The two water molecules
were close to many inhibitors, and seemed to play two roles: maintaining the
orientation of the Glu205 and Glu206 side chains through a network via the water
molecules, and arranging the inhibitor appropriately at the S2 subsite.
CONCLUSIONS: Our study based on high-quality resources may provide a necessary
minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is
commercially useful.
PMID- 27491542
TI - Outcomes of surgical aortic valve replacement using Carpentier-Edwards PERIMOUNT
bioprosthesis series in elderly patients with severe aortic valve stenosis: a
retrospective cohort study.
AB - OBJECTIVE: We sought to compare the outcomes of Carpentier-Edwards PERIMOUNT
(CEP), Magna and Magna Ease valves in Japanese elderly patients with severe
aortic valve stenosis (AS). METHODS: We retrospectively identified 136 patients
(mean age 76.61 +/- 5.5 years old) who had undergone isolated surgical aortic
valve replacement (SAVR) using CEP, Magna, and Magna Ease valves at a single
institution, from January 2001 to December 2013. We compared the valves according
to their survival rates, freedom from major adverse cardiovascular and
cerebrovascular events (MACCE), and durability and hemodynamic performance by
echocardiographic data. RESULTS: The thirty-day mortality after isolated SAVR in
all the valve groups was "zero". The differences among the three groups in terms
of survival rates, freedom from MACCE at 2 years, durability and hemodynamic
performance of the valves by echocardiographic data was not statistically
significant. CONCLUSION: All CEP, Magna and Magna Ease valves seemed to be
similarly useful in Japanese elderly patients with severe AS. Our data did not
clearly support the superiority of one valve over another. A longer follow-up
period might be necessary to compare the durability and hemodynamic performance
of these valves with more certainty.
PMID- 27491543
TI - Structure of the Saccharomyces cerevisiae Hrr25:Mam1 monopolin subcomplex reveals
a novel kinase regulator.
AB - In budding yeast, the monopolin complex mediates sister kinetochore cross-linking
and co-orientation in meiosis I. The CK1delta kinase Hrr25 is critical for sister
kinetochore co-orientation, but its roles are not well understood. Here, we
present the structures of Hrr25 and its complex with the monopolin subunit Mam1.
Hrr25 possesses a "central domain" that packs tightly against the kinase C-lobe,
adjacent to the binding site for Mam1. Together, the Hrr25 central domain and
Mam1 form a novel, contiguous embellishment to the Hrr25 kinase domain that
affects Hrr25 conformational dynamics and enzyme kinetics. Mam1 binds a
hydrophobic surface on the Hrr25 N-lobe that is conserved in CK1delta-family
kinases, suggesting a role for this surface in recruitment and/or regulation of
these enzymes throughout eukaryotes. Finally, using purified proteins, we find
that Hrr25 phosphorylates the kinetochore receptor for monopolin, Dsn1. Together
with our new structural insights into the fully assembled monopolin complex, this
finding suggests that tightly localized Hrr25 activity modulates monopolin
complex-kinetochore interactions through phosphorylation of both kinetochore and
monopolin complex components.
PMID- 27491544
TI - Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Ganglia of
Human Gastrointestinal Tract.
AB - CF is caused by mutations of the gene encoding the cystic fibrosis transmembrane
conductance regulator (CFTR) which is an anion selective transmembrane ion
channel that mainly regulates chloride transport, expressed in the epithelia of
various organs. Recently, we have demonstrated CFTR expression in the brain, the
spinal cord and the sympathetic ganglia. This study aims to investigate the
expression and distribution of CFTR in the ganglia of the human gastrointestinal
tract. Fresh tissue and formalin-fixed paraffin-embedded normal gastrointestinal
tract samples were collected from eleven surgical patients and five autopsy
cases. Immunohistochemistry, in situ hybridization, laser-assisted
microdissection and nested reverse transcriptase polymerase chain reaction were
performed. Expression of CFTR protein and mRNA was detected in neurons of the
ganglia of all segments of the human gastrointestinal tract examined, including
the stomach, duodenum, jejunum, ileum, cecum, appendix, colon and rectum. The
extensive expression of CFTR in the enteric ganglia suggests that CFTR may play a
role in the physiology of the innervation of the gastro-intestinal tract. The
presence of dysfunctional CFTRs in enteric ganglia could, to a certain extent,
explain the gastrointestinal symptoms frequently experienced by CF patients.
PMID- 27491545
TI - Cost of diabetic retinopathy and macular oedema in a population, an eight year
follow up.
AB - BACKGROUND: Prospective, population-based study of an 8-year follow up. To
determine the direct cost of diabetic retinopathy [DR], evaluating our screening
programme and the cost of treating DR, focusing on diabetic macular oedema [DMO]
after anti-vascular endothelial growth factor [anti-VEGF] treatment. METHODS: A
total of 15,396 diabetes mellitus [DM] patients were studied. We determined the
cost-effectiveness of our screening programme against an annual programme by
applying the Markov simulation model. We also compared the cost-effectiveness of
anti-VEGF treatment to laser treatment for screened patients with DMO. RESULTS:
The cost of our 2.5-year screening programme was as follows: per patient with any
DR, ?482.85 +/- 35.14; per sight-threatening diabetic retinopathy [STDR] patient,
?1528.26 +/- 114.94; and ?1826.98 +/- 108.26 per DMO patient. Comparatively, an
annual screening programme would result in increases as follows: 0.77 in QALY per
patient with any-DR and 0.6 and 0.44 per patient with STDR or DMO, respectively,
with an incremental cost-effective ratio [ICER] of ?1096.88 for any-DR, ?4571.2
for STDR and ?7443.28 per DMO patient. Regarding diagnosis and treatment, the
mean annual total cost per patient with DMO was ?777.09 +/- 49.45 for the laser
treated group and ?7153.62 +/- 212.15 for the anti-VEGF group, with a QALY gain
of 0.21, the yearly mean cost was ?7153.62 +/- 212.15 per patient, and the ICER
was ?30,361. CONCLUSIONS: Screening for diabetic retinopathy every 2.5 years is
cost-effective, but should be adjusted to a patient's personal risk factors.
Treatment with anti-VEGF for DMO has increased costs, but the cost-utility
increases to 0.21 QALY per patient.
PMID- 27491546
TI - Engineering Saccharomyces cerevisiae with the deletion of endogenous glucosidases
for the production of flavonoid glucosides.
AB - BACKGROUND: Glycosylation of flavonoids is a promising approach to improve the
pharmacokinetic properties and biological activities of flavonoids. Recently,
many efforts such as enzymatic biocatalysis and the engineered Escherichia coli
biotransformation have increased the production of flavonoid glucosides. However,
the low yield of flavonoid glucosides can not meet the increasing demand for
human medical and dietary needs. Saccharomyces cerevisiae is a generally regarded
as safe (GRAS) organism that has several attractive characteristics as a
metabolic engineering platform for the production of flavonoid glucosides.
However, endogenous glucosidases of S. cerevisiae as a whole-cell biocatalyst
reversibly hydrolyse the glucosidic bond and hinder the biosynthesis of the
desired products. In this study, a model flavonoid, scutellarein, was used to
exploit how to enhance the production of flavonoid glucosides in the engineered
S. cerevisiae. RESULTS: To produce flavonoid glucosides, three flavonoid
glucosyltransferases (SbGTs) from Scutellaria baicalensis Georgi were
successfully expressed in E. coli, and their biochemical characterizations were
identified. In addition, to synthesize the flavonoid glucosides in whole-cell S.
cerevisiae, SbGT34 was selected for constructing the engineering yeast. Three
glucosidase genes (EXG1, SPR1, YIR007W) were knocked out using homologous
integration, and the EXG1 gene was determined to be the decisive gene of S.
cerevisiae in the process of hydrolysing flavonoid glucosides. To further enhance
the potential glycosylation activity of S. cerevisiae, two genes encoding
phosphoglucomutase and UTP-glucose-1-phosphate uridylyltransferase involved in
the synthetic system of uridine diphosphate glucose were over-expressed in S.
cerevisiae. Consequently, approximately 4.8 g (1.2 g/L) of scutellarein 7-O
glucoside (S7G) was produced in 4 L of medium after 54 h of incubation in a 10-L
fermenter while being supplied with ~3.5 g of scutellarein. CONCLUSIONS: The
engineered yeast harbouring SbGT with a deletion of glucosidases produced more
flavonoid glucosides than strains without a deletion of glucosidases. This
platform without glucosidase activity could be used to modify a wide range of
valued plant secondary metabolites and to explore of their biological functions
using whole-cell S. cerevisiae as a biocatalyst.
PMID- 27491547
TI - Empirical determination of breed-of-origin of alleles in three-breed cross pigs.
AB - BACKGROUND: Although breeding programs for pigs and poultry aim at improving
crossbred performance, they mainly use training populations that consist of
purebred animals. For some traits, e.g. residual feed intake, the genetic
correlation between purebred and crossbred performance is low and thus including
crossbred animals in the training population is required. With crossbred animals,
the effects of single nucleotide polymorphisms (SNPs) may be breed-specific
because linkage disequilibrium patterns between a SNP and a quantitative trait
locus (QTL), and allele frequencies and allele substitution effects of a QTL may
differ between breeds. To estimate the breed-specific effects of alleles in a
crossbred population, the breed-of-origin of alleles in crossbred animals must be
known. This study was aimed at investigating the performance of an approach that
assigns breed-of-origin of alleles in real data of three-breed cross pigs.
Genotypic data were available for 14,187 purebred, 1354 F1, and 1723 three-breed
cross pigs. RESULTS: On average, 93.0 % of the alleles of three-breed cross pigs
were assigned a breed-of-origin without using pedigree information and 94.6 %
with using pedigree information. The assignment percentage could be improved by
allowing a percentage (fr) of the copies of a haplotype to be observed in a
purebred population different from the assigned breed-of-origin. Changing fr from
0 to 20 %, increased assignment of breed-of-origin by 0.6 and 0.7 % when pedigree
information was and was not used, respectively, which indicates the benefit of
setting fr to 20 %. CONCLUSIONS: Breed-of-origin of alleles of three-breed cross
pigs can be derived empirically without the need for pedigree information, with
93.7 % of the alleles assigned a breed-of-origin. Pedigree information is useful
to reduce computation time and can slightly increase the percentage of
assignments. Knowledge on the breed-of-origin of alleles allows the use of models
that implement breed-specific effects of SNP alleles in genomic prediction, with
the aim of improving selection of purebred animals for crossbred offspring
performance.
PMID- 27491548
TI - Bioelectrical impedance vector analysis as a useful predictor of nutritional
status in patients with short bowel syndrome.
AB - BACKGROUND & AIMS: Short bowel syndrome (SBS) represents a serious intestinal
absorption disorder. Therefore, patients with SBS may have severe malnutrition
and excessive mineral and fluid losses. Once the assessment of nutritional status
is important in their follow-up, body composition measurements and especially
total body water (TBW) must be repeatedly evaluated for the assessment of changes
in hydration and nutritional care. The aim of this study was to investigate if
bioelectrical impedance vector analysis (BIVA) is a useful predictor of
nutritional and hydration status in SBS patients. METHODS: In this observational
study, 22 participants (12 women), 11 with SBS and 11 gender, age and BMI-matched
controls, were evaluated using the bioelectrical impedance measurements (BIA) and
BIVA to assess nutritional and hydration status. RESULTS: Participants age was 53
+/- 8 y (mean +/- SD). Body water, fat mass and lean mass as assessed by BIA did
not differ between the two groups. However, BIVA showed important differences
between the groups regarding hydration and amount of soft tissue (p < 0.0001 for
women and p = 0.0015 for men). The results also evidenced that women's vectors
were related to cachexia, while men's vectors were divided into lean and cachexia
quadrants. The use of BIVA analysis also evidenced hydration disturbance and
losses of soft tissue. CONCLUSIONS: BIVA may represent a better predictor of
nutritional status for analysis and interpretation of body composition in
patients with short bowel syndrome. This trial was registered at
ClinicalTrials.gov as NCT02113228.
PMID- 27491549
TI - [Mediastinal germ cell tumors].
AB - The mediastinum is among the most frequent anatomic region in which germ cell
tumors (GCT) arise, second only to the gonads. Mediastinal GCT (mGCT) account for
16 % of all mediastinal neoplasms. Although the morphology and (according to all
available data) the molecular genetics of mediastinal and gonadal GCT are
identical, a number of unique aspects exist. There is a highly relevant bi-modal
age distribution. In pre-pubertal children of both sexes, mGCT consist
exclusively of teratomas and yolk sac tumors. The prognosis is generally
favorable with modern treatment. In post-pubertal adults, virtually all patients
with malignant mGCT are males; the prognosis is more guarded and depends (among
other factors) on the histological GCT components and is similar to GCT in other
organs. So-called somatic type malignancies (i. e. clonally related, non-germ
cell neoplasias arising in a GCT) are much more frequent in mGCT than in other
organs, and the association between mediastinal yolk sac tumors and hematological
malignancies, such as myelodysplasias and leukemias, is unique to mediastinal
tumors. The prognosis of GCT with somatic type malignancies is generally dismal.
PMID- 27491550
TI - Physiological characteristics and metabolomics of transgenic wheat containing the
maize C4 phosphoenolpyruvate carboxylase (PEPC) gene under high temperature
stress.
AB - In this paper, two transgenic wheat lines, PC27 and PC51, containing the maize
PEPC gene and its wild-type (WT) were used as experimental material to study the
effects of high temperature on their photosynthetic physiological characteristics
and metabolome. The results showed that transgenic wheat lines had higher
photosynthetic rate (P n) than WT under non-stress treatment (NT) and high
temperature stress treatment (HT), and more significantly under HT. The change
trends of F v/F m, F PSII, and q P were similar to P n, whereas that of non
photochemical quenching (NPQ) was the opposite. Compared with WT, no differences
in chlorophyll content between the transgenic wheat and WT were observed under
NT, but two transgenic lines had relatively higher contents than WT under HT. The
change trends of Chlorophyll a/b radio, the decreased values of F m, Wk, and Vj,
and the activity of the antioxidant enzyme were consistent with the chlorophyll
content. Compared with WT, transgenic wheat lines exhibited lower rate of
superoxide anion production, H2O2 and malondialdehyde content under HT, and no
significant differences were observed under NT. The expression pattern of the
ZmPEPC gene and wheat endogenous photosynthesis-related genes were in agreement
with that of P n. Compared with WT, about 13 different metabolites including one
organic acid, six amino acids, four sugars, and two polyols were identified under
NT; 25 different metabolites including six organic acids, 12 amino acids, four
sugars, and three polyols were identified under HT. Collectively, our results
indicate that ZmPEPC gene can enhance photochemical and antioxidant enzyme
activity, upregulate the expression of photosynthesis-related genes, delay
degradation of chlorophyll, change contents of proline and other metabolites in
wheat, and ultimately improves its heat tolerance.
PMID- 27491551
TI - Cortical miscommunication after prenatal exposure to alcohol.
AB - We report on the effects of prenatal alcohol exposure on resting-state brain
activity as measured by magnetoencephalography (MEG). We studied 37 subjects
diagnosed with fetal alcohol spectrum disorder in one of three categories: fetal
alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related
neurodevelopmental disorder. For each subject, the MEG signal was recorded for 60
s during rest while subjects lay supine. Using time series analysis, we
calculated the synchronous neural interactions for all pair-wise combinations of
248 MEG sensors resulting in 30,628 partial correlations for each subject. We
found significant differences from control subjects in 6.19 % of the partial zero
lag crosscorrelations (synchronous neural interactions; Georgopoulos et al. in J
Neural Eng 4:349-355, 2007), with these differences localized in the right
posterior frontal, right parietal, and left parietal/posterior frontal regions.
These results show that MEG can detect functional brain differences in the
individuals affected by prenatal exposure to alcohol. Furthermore, these
differences may serve as a biomarker for future studies linking symptoms and
signs to specific brain areas. This may lead to new insights into the
neuropathology of fetal alcohol spectrum disorders.
PMID- 27491552
TI - Quantitative and qualitative insights into the experiences of children with Rett
syndrome and their families.
AB - Rett syndrome is a rare neurodevelopmental disorder caused by a mutation in the
MECP2 gene. It is associated with severe functional impairments and medical
comorbidities such as scoliosis and poor growth. The population-based and
longitudinal Australian Rett Syndrome Database was established in 1993 and has
supported investigations of the natural history of Rett syndrome and
effectiveness of treatments, as well as a suite of qualitative studies to
identify deeper meanings. This paper describes the early presentation of Rett
syndrome, including regression and challenges for families seeking a diagnosis.
We discuss the importance of implementing strategies to enhance daily
communication and movement, describe difficulties interpreting the presence of
pain and discomfort, and argue for a stronger evidence base in relation to
management. Finally, we outline a framework for understanding quality of life in
Rett syndrome and suggest areas of life to which we can direct efforts in order
to improve quality of life. Each of these descriptions is illustrated with
vignettes of child and family experiences. Clinicians and researchers must
continue to build this framework of knowledge and understanding with efforts
committed to providing more effective treatments and supporting the best quality
of life for those affected.
PMID- 27491553
TI - Progress in Rett Syndrome: from discovery to clinical trials.
AB - Fifty years ago, Andreas Rett described a disorder in 22 females featuring
prominent regression of fine motor and communication skills, cognitive
impairment, stereotypic movements, periodic breathing, and gait abnormalities.
This disorder became known as Rett syndrome (RTT) following the report of Hagberg
et al. in 1983. Although RTT was scarcely recognized at that time in the United
States, here the efforts of Rett and Hagberg led to rapid progress in recognition
and diagnosis, a clearer understanding of its clinical and pathological
underpinnings, and, ultimately, identification of mutations in the methyl-CpG
binding protein 2 (MECP2) gene as the primary cause of this unique and
challenging neurodevelopmental disorder. Thereafter, a natural history study and
critical translational research in animal models paved the way for potential
disease-modifying agents to be assessed in human clinical trials. To be
successful, the energies of the international community at all levels, including
researchers in clinical and basic science, funding agencies, pharmaceutical
companies, patient advocates, and, above all, parents and their children are
essential. Otherwise, hopes for effective treatment, if not, a cure, will remain
unfulfilled.
PMID- 27491554
TI - The changing faces of corticotroph cell adenomas: the role of prohormone
convertase 1/3.
AB - The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent
corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas
associated with Cushing's disease (CD). The aim of the study was to investigate
the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into
CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures
for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA.
During the follow-up, three patients with SCA showed a clear transformation from
SCA into CD and underwent surgery once again to remove the recurrent tumour. The
PC1/3 expression was analysed by both immunohistochemistry and quantitative real
time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The
immunohistochemical PC1/3 expression was negative or weak in the three patients
in the initial phase of SCA, while a strong expression was observed in the
majority of neoplastic cells in tissue specimens obtained from the same three
patients at the time of recurrence as CD. The immunohistochemical PC1/3
expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR.
In 14 cases of SCA with no change of phenotype during the follow-up, the
immunohistochemical PC1/3 expression was low and strictly associated with the
level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent
tumours (4/4 cases). Our study provides insight into the crucial role of the
PC1/3 protein in the transformation of phenotype from SCA to CD.
PMID- 27491555
TI - A hypothetical model to solve the controversy over the involvement of UCP2 in
palmitate-induced beta-cell dysfunction.
AB - The aim of this article is to solve an existing controversy over the involvement
of uncoupling protein-2 in the impairment of glucose-stimulated insulin secretion
induced by chronic exposure of beta-cells to palmitate. We analyzed and compared
the results of studies that support and that deny the involvement of uncoupling
protein-2 in this impairment. We observed that this impairment could occur in
multiple stages. We provide a model in which palmitate-induced impairment of
glucose-stimulated insulin secretion is proposed to occur in two stages, early
stage and late stage, depending on the integrity of electron supply (glycolysis
and Krebs cycle) and transport system through electron transport chain after
palmitate treatment. Prolonged exposure of beta-cells to palmitate can impair
this system. Early-stage impairment occurs due to uncoupling by uncoupling
protein-2 when this system is still intact. When this system becomes impaired,
late-stage impairment occurs mainly due to reduced glucose-stimulated adenosine
triphosphate production independent of uncoupling by uncoupling protein-2. The
change in glucose-stimulated oxygen uptake after palmitate treatment reflects the
integrity of this system and can be used to differentiate between the two stages.
Some beta-cells lines and islets appear to be more resistant to palmitate-induced
impairment of electron supply and transport system than others, and therefore
early stage is prominent in the more resistant cell lines and less prominent or
absent in the less resistant cell lines. This may help to resolve the
pathogenesis of diabetes and to monitor the progression of palmitate-induced beta
cell dysfunction.
PMID- 27491557
TI - In Search of Cognitive Dignity: The Diagnostic Challenges of Primary Care.
PMID- 27491556
TI - WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers -
a short report.
AB - PURPOSE: Oral squamous cell carcinoma (OSCC) is a frequently occurring aggressive
malignancy with a heterogeneous clinical behavior. Based on the paucity of
specific early diagnostic and prognostic biomarkers, which hampers the
appropriate treatment and, ultimately the development of novel targeted
therapies, we aimed at identifying such biomarkers through a genetic and
epigenetic analysis of these tumors. METHODS: 93 primary OSCCs were subjected to
DNA copy number alteration (CNA) and methylation status analyses using
methylation-specific multiplex ligation-dependent probe amplification (MS-MPLA).
The genetic and epigenetic OSCC profiles obtained were associated with the
patients' clinic-pathological features. RESULTS: We found that WT1 gene promoter
methylation is a predictor of a better prognosis and that MSH6 and GATA5 gene
promoter methylation serve as predictors of a worse prognosis. GATA5 gene
promoter methylation was found to be significantly associated with a shorter
survival rate. In addition, we found that PAX5 gene promoter methylation was
significantly associated with tongue tumors. To the best of our knowledge, this
is the first study that highlights this specific set of genes as epigenetic
diagnostic and prognostic biomarkers in OSCC. CONCLUSIONS: Our data highlight the
importance of epigenetically assessing OSCCs to identify key genes that may serve
as diagnostic and prognostic biomarkers and, potentially, as candidate
therapeutic targets.
PMID- 27491558
TI - Risk Assessment for Venous Thromboembolism in Chemotherapy-Treated Ambulatory
Cancer Patients.
AB - OBJECTIVE: To design a precision medicine approach aimed at exploiting
significant patterns in data, in order to produce venous thromboembolism (VTE)
risk predictors for cancer outpatients that might be of advantage over the
currently recommended model (Khorana score). DESIGN: Multiple kernel learning
(MKL) based on support vector machines and random optimization (RO) models were
used to produce VTE risk predictors (referred to as machine learning [ML]-RO)
yielding the best classification performance over a training (3-fold cross
validation) and testing set. RESULTS: Attributes of the patient data set ( n =
1179) were clustered into 9 groups according to clinical significance. Our
analysis produced 6 ML-RO models in the training set, which yielded better
likelihood ratios (LRs) than baseline models. Of interest, the most significant
LRs were observed in 2 ML-RO approaches not including the Khorana score (ML-RO-2:
positive likelihood ratio [+LR] = 1.68, negative likelihood ratio [-LR] = 0.24;
ML-RO-3: +LR = 1.64, -LR = 0.37). The enhanced performance of ML-RO approaches
over the Khorana score was further confirmed by the analysis of the areas under
the Precision-Recall curve (AUCPR), and the approaches were superior in the ML-RO
approaches (best performances: ML-RO-2: AUCPR = 0.212; ML-RO-3-K: AUCPR = 0.146)
compared with the Khorana score (AUCPR = 0.096). Of interest, the best-fitting
model was ML-RO-2, in which blood lipids and body mass index/performance status
retained the strongest weights, with a weaker association with tumor site/stage
and drugs. CONCLUSIONS: Although the monocentric validation of the presented
predictors might represent a limitation, these results demonstrate that a model
based on MKL and RO may represent a novel methodological approach to derive VTE
risk classifiers. Moreover, this study highlights the advantages of optimizing
the relative importance of groups of clinical attributes in the selection of VTE
risk predictors.
PMID- 27491559
TI - Neo-tanshinlactone selectively inhibits the proliferation of estrogen receptor
positive breast cancer cells through transcriptional down-regulation of estrogen
receptor alpha.
AB - Breast cancer, the most frequent cancer in women, is the second leading cause of
cancer-related death. Estrogens and estrogen receptors are well recognized to
play predominant roles in breast cancer development and growth. Neo
tanshinlactone is a natural product isolated from Salvia miltiorrhiza and showed
selective growth inhibition of ER+ breast cancer cell lines as demonstrated by
cell proliferation assay and colony formation assay. The selective anti
proliferative effect of neo-tanshinlactone was associated with the induction of
apoptosis in ER+ breast cancer cells. We also found that neo-tanshinlactone
decreased steady state ESR1 mRNA levels in ER+ breast cancer cells, which was
further confirmed by analysis of ER protein levels as well as the mRNA levels of
target genes of this transcription factor, such as ESR2, BRCA1, CCND1, GREB1,
TFF1, SERPINB9 and ABCA3. Furthermore, analysis of heterogeneous nuclear RNA
(hnRNA) demonstrated that neo-tanshinlactone inhibited ESR1 mRNA de novo
synthesis. The decrease of steady state ESR1 mRNA upon neo-tanshinlactone
treatment was not abolished by protein synthesis inhibitor cycloheximide. And
inhibition of mRNA synthesis with actinomycin D revealed no significant effect of
neo-tanshinlactone on ESR1 mRNA stability. These results indicated that
transcriptional down-regulation of ESR1 mRNA could contribute to the selective
activity of neo-tanshinlactone on ER+ breast cancer cells. And as expected, the
combination of neo-tanshinlactone and antiestrogen reagent tamoxifen showed a
synergistic effect on growth of ER+ MCF7 cells. Our results suggest that neo
tanshinlactone is a promising regimen for ER+ breast tumors.
PMID- 27491560
TI - Stimulation of the histamine 4 receptor upregulates thymic stromal lymphopoietin
(TSLP) in human and murine keratinocytes.
AB - The cytokine thymic stromal lymphopoietin (TSLP) is involved in the development
and the progression of allergic diseases. It is mainly released by epithelial
cells at barriers such as skin and gut in response to danger signals.
Overexpression of TSLP in keratinocytes (KC) can provoke the development of a
type 2 inflammatory response. Additionally, TSLP directly acts on sensory neurons
and thereby triggers itch. Since histamine is also increased in lesions of
inflammatory skin diseases, the aim of this study was to investigate possible
effects of histamine as well as different histamine receptor subtype agonists and
antagonists on TSLP production in KC. We therefore stimulated human KC with
histamine in the presence or absence of the known TSLP-inductor poly I:C and
measured TSLP production at protein as well as mRNA level. Histamine alone did
not induce TSLP production in human KC, but pre-incubation with histamine prior
to challenge with poly I:C resulted in a significant increase of TSLP production
compared to stimulation with poly I:C alone. Experiments with different histamine
receptor agonists (H1R: 2-pyridylethylamine; H2R: amthamine; H2R/H4R: 4
methylhistamine (4MH)) revealed a dominant role for the H4R receptor, as 4-MH in
combination with poly I:C displayed a significant increase of TSLP secretion,
while the other agonists did not show any effect. The increase in TSLP production
by 4MH was blocked with the H4R antagonist JNJ7777120. This effect was
reproducible also in the murine KC cell line MSC. Taken together, our study
indicates a new role for the H4 receptor in the regulation of TSLP in
keratinocytes. Therefore, blocking of the H4R receptor in allergic diseases might
be promising to alleviate inflammation and pruritus via TSLP.
PMID- 27491561
TI - Epistemic injustice and responsibility in borderline personality disorder.
AB - Miranda Fricker's concept of epistemic injustice has been quite a novel idea in
epistemology. It brings something new to the fields of epistemology and ethics.
Fricker draws our attention to a distinctive species of injustice, the epistemic
injustice, in which someone is specifically wronged in his capacity as a knower.
There has been a significant amount of work done in epistemic injustice, both in
race and gender studies. The application of the concept in the context of mental
health is less explored. Here, we aim to apply the concept of epistemic injustice
in attributing responsibility to patients with borderline personality disorder.
Attributing responsibility involves holding someone accountable for his presumed
wrongdoings, making judgments on whether the agent has control on his action, on
whether is aware of its consequences. It is generally agreed that in order to be
morally responsible for an action the person should be worthy of praise or blame
for it. Following Aristotle, we focus on epistemic condition in attribution of
responsibility. We will discuss the role of epistemic injustice in assessment of
epistemic condition of responsibility. We will show that we can misinterpret the
agent's intentions because of the presence of systematic prejudices. We will
focus on patients suffering from borderline personality disorder. We provide a
case vignette to show a tendency in the professionals in holding these patients
responsible for their action when it can be argued otherwise. We argue that
prejudice against the patient with borderline personality disorder where the
person is seen as manipulative plays a significant role in the process of
epistemic injustice. The suggested manipulative nature of patients with
borderline personality disorder leads to professionals to ascribe agency and
knowledge where it is not due.
PMID- 27491562
TI - Methadone analgesia in the critically ill.
PMID- 27491563
TI - Use of ultrasound guidance for central venous catheterization: a national survey
of intensivists and hospitalists.
AB - PURPOSE: The purpose of the study is to evaluate the frequency and barriers to
use of ultrasound guidance for central venous catheter (CVC) insertion by
physicians specializing in critical care and hospital medicine. MATERIALS AND
METHODS: A national cross-sectional electronic survey of intensivists and
hospitalists was administered from November 2014 to January 2015. RESULTS: The
survey response rate was 5.9% (1013/17 233). Moderate to very frequent use of
ultrasound guidance varied by site: internal jugular vein (80%), subclavian vein
(31%), and femoral vein (45%). Nearly all physicians (99%) who insert internal
jugular CVCs daily use ultrasound guidance, whereas only 46% of physicians who
insert subclavian CVCs daily use ultrasound guidance. Use of real-time ultrasound
guidance varied by insertion site: internal jugular vein (73%), subclavian vein
(28%), and femoral vein (42%). Most physicians (59%) reported not being
comfortable with real-time needle tracking at the subclavian site. The most
frequently reported barriers to use of ultrasound guidance were (1) limited
availability of ultrasound equipment (28%), (2) perception of increased total
procedure time (22%), and (3) concern for loss of landmark skills (13%).
CONCLUSIONS: Most intensivists routinely use ultrasound guidance to insert
internal jugular CVCs but not subclavian CVCs. The most commonly reported barrier
to ultrasound use was limited access to an ultrasound machine.
PMID- 27491564
TI - Retinoid-related orphan receptor gamma (RORgamma) adult induced knockout mice
develop lymphoblastic lymphoma.
AB - RORgamma is a nuclear hormone receptor which controls polarization of naive CD4+
T-cells into proinflammatory Th17 cells. Pharmacological antagonism of RORgamma
has therapeutic potential for autoimmune diseases; however, this mechanism may
potentially carry target-related safety risks, as mice deficient in Rorc, the
gene encoding RORgamma, develop T-cell lymphoma with 50% frequency. Due to the
requirement of RORgamma during development, the Rorc knockout (KO) animals lack
secondary lymphoid organs and have a dysregulation in the generation of CD4+ and
CD8+ T cells. We wanted to extend the evaluation of RORgamma deficiency to
address the question whether lymphomas, similar to those observed in the Rorc KO,
would develop in an animal with an otherwise intact adult immune system.
Accordingly, we designed a conditional RORgamma knockout mouse (Rorc CKO) where
the Rorc locus could be deleted in adult animals. Based on these studies we can
confirm that these animals also develop lymphoma in a similar time frame as
embryonic Rorc knockouts. This study also suggests that in animals where the gene
deletion is incomplete, the thymus undergoes a rapid selection process replacing
Rorc deficient cells with remnant thymocytes carrying a functional Rorc locus and
that subsequently, these animals do not develop lymphoblastic lymphoma.
PMID- 27491566
TI - Pitfalls in lupus.
AB - "The objective of Pitfall!TM is to guide Harry through a maze of jungle scenes,
jumping over or avoiding many deadly dangers... Harry has three lives in each
game." If you exchange Harry's adventures with "Life with SLE," patients have to
be guided through the jungle having just one life and the deadly dangers are
flares, organ manifestations, and, e.g., consequences of immunosuppressive
medications, especially glucocorticoids. Monitoring and treatment in line with
recommendations and guidelines may be supportive to survive the first 3 to 5
levels in most cases, but for higher levels of the reality game, creativity is
needed and life becomes more risky. The aim of this reflection is to identify
common pitfalls and to stimulate further research and collaboration in specific
areas of the lupus jungle. Topics like "Hidden Power Unit," "Looks similar ...,"
"Rev Meter for SLE," "Flare Prediction," "Level 2: Eminence Based,"
"Lupus=Lifelong Immunosuppression?!," "Glucocorticoids," "Antimalarials Are
Contraindicated," "It Is All About Immunosuppression," "Prediction of Damage,"
and "Patient Global Assessment (PGA) versus Physician Global Assessment (PhGA)"
are addressed. Raised ideas and thoughts are by no means complete or exclusive,
but if taken up, they may hopefully lead to another approach in daily care and
trials in SLE.
PMID- 27491565
TI - Humoral and cellular autoimmunity in women with recurrent pregnancy losses and
repeated implantation failures: A possible role of vitamin D.
AB - Women with recurrent pregnancy losses (RPL) and repeated implantation failures
(RIF) have auto- and cellular immune abnormalities. Approximately, 20% of women
with RPL have autoimmune abnormalities, particularly antiphospholipid antibodies
(APA). In addition, these women have a higher prevalence of antinuclear antibody,
anti-thyroperoxidase and anti-thyroglobulin antibodies, and other non-organ
specific autoantibodies. In women with RPL, the presence of autoimmunity is often
associated with cellular immune abnormalities, such as increased NK cell levels
and Th1/Th2 cell ratios. Vitamin D (VD) plays a major role in regulation of auto-
and cellular immune abnormalities. VD deficiency is prevalent in women with RPL,
and women with VD deficiency have increased auto- and cellular immune
abnormalities as compared with women with normal VD levels. VD has immune
regulatory effects on various immune effectors including T, B and NK cells.
Potential therapeutic application of VD for RPL and RIF with auto- and cellular
immune abnormalities should be explored.
PMID- 27491567
TI - The viral paradigm in type 1 diabetes: Who are the main suspects?
AB - Type 1 diabetes (T1D) is an autoimmune disease characterized by the loss of
pancreatic beta cells in the islets of Langerhans. Although genetic
predisposition plays an important role in T1D development, studies of identical
twins suggest that environmental factors such as viruses and other pathogens may
be critical triggers either through direct cytolytic effect and gradual beta cell
destruction, or by bystander activation of the immune system. In addition,
viruses may circumvent the host immune response and have the capacity to
establish chronic lifelong infections. The association of various viral
infections with the induction of T1D has been extensively studied at the
serological and epidemiological level. However, there is still little evidence
from studies of human pancreas to confirm their presence or a causal role in
disease pathogenesis. In this review, we identify possible suspects for viral
triggers of disease and explain their potential roles in the "viral paradigm" of
T1D.
PMID- 27491569
TI - Fc-gamma receptors: Attractive targets for autoimmune drug discovery searching
for intelligent therapeutic designs.
AB - Autoantibody immune complexes (ICs) mediate pathogenesis in multiple autoimmune
diseases via direct interference with target function, complement fixation, and
interaction with Fc-gamma receptors (FcgammaRs). Through high avidity
interactions, ICs are able to crosslink low affinity FcgammaRs expressed on a
wide variety of effector cells, leading to secretion of pro-inflammatory
mediators and inducing cytotoxicity, ultimately resulting in tissue injury. Given
their relevance in numerous autoimmune diseases, FcgammaRs have been considered
as attractive therapeutic targets for the last three decades. However, a limited
number of investigational drug candidates have been developed targeting FcgammaRs
and only a few approved therapeutics have been associated with impacting
FcgammaRs. This review provides a historical overview of the different
therapeutic approaches used to target FcgammaRs for the treatment of autoimmune
and inflammatory diseases.
PMID- 27491568
TI - Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies:
A history of statins and experience from a large international multi-center
study.
AB - In an effort to find naturally occurring substances that reduce cholesterol by
inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were
first discovered by Endo in 1972. With the widespread prescription and use of
statins to decrease morbidity from myocardial infarction and stroke, it was noted
that approximately 5% of all statin users experienced muscle pain and weakness
during treatment. In a smaller proportion of patients, the myopathy progressed to
severe morbidity marked by proximal weakness and severe muscle wasting.
Remarkably, Mammen and colleagues were the first to discover that the molecular
target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an
autoantibody target in patients that develop an immune-mediated necrotizing
myopathy (IMNM). These observations have been confirmed in a number of studies
but, until today, a multi-center, international study of IMNM, related idiopathic
inflammatory myopathies (IIM), other auto-inflammatory conditions and controls
has not been published. Accordingly, an international, multi-center study
investigated the utility of anti-HMGCR antibodies in the diagnosis of statin
associated IMNM in comparison to different forms of IIM and controls. This study
included samples from patients with different forms of IIM (n=1250) and patients
with other diseases (n=656) that were collected from twelve sites and tested for
anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR
autoantibodies, when found in conjunction with statin use, characterize a subset
of IIM who are older and have necrosis on muscle biopsy. Taken together, the data
to date indicates that testing for anti-HMGCR antibodies is important in the
differential diagnosis of IIM and might be considered for future classification
criteria.
PMID- 27491570
TI - The role of monocytes in ANCA-associated vasculitides.
AB - The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a
heterogeneous group of diseases causing inflammation in small blood vessels and
linked by the presence of circulating ANCA specific for proteinase 3 (PR3) or
myeloperoxidase (MPO). These antigens are present both in the cytoplasmic
granules and on the surface of neutrophils, and the effect of ANCA on neutrophil
biology has been extensively studied. In contrast, less attention has been paid
to the role of monocytes in AAV. These cells contain PR3 and MPO in lysosomes and
can also express them at the cell surface. Monocytes respond to ANCA by producing
pro-inflammatory and chemotactic cytokines, reactive-oxygen-species and by up
regulating CD14. Moreover, soluble and cell surface markers of monocyte
activation are raised in AAV patients, suggesting an activated phenotype that may
persist even during disease remission. The presence of monocyte-derived
macrophages and giant cells within damaged renal and vascular tissue in AAV also
attests to their role in pathogenesis. In particular, their presence in the
tertiary lymphoid organ-like granulomas of AAV patients may generate an
environment predisposed to maintaining autoimmunity. Here we discuss the evidence
for a pathogenic role of monocytes in AAV, their role in granuloma formation and
tissue damage, and their potential to both direct and maintain autoimmunity. ANCA
activation of monocytes may therefore provide an explanation for the relapsing
remitting course of disease and its links with infections. Monocytes may thus
represent a promising target for the treatment of this group of life-threatening
diseases.
PMID- 27491571
TI - The result of surgical treatment of medial epicondylitis: analysis with more than
a 5-year follow-up.
AB - BACKGROUND: Angiofibroblastic changes of a musculotendinous origin at the medial
epicondyle characterize medial epicondylitis of the elbow. Although nonsurgical
treatment is the primary approach for medial epicondylitis, surgical treatment
should be considered when conservative therapy fails. This study reports the
results of surgical treatment of medial epicondylitis monitored for more than 5
years. METHODS: This study included 55 patients with 63 cases of medial
epicondylitis between 2000 and 2010. The conservative treatment periods lasted
for a minimum of 1 year, and steroid injections were administered more than twice
before surgery. One surgeon conducted the surgical procedures. The Nirschl and
Pettrone grades, visual analog scale (VAS) scores, Disabilities of the Arm,
Shoulder and Hand (DASH) scores, Mayo Elbow Performance scores, and grip
strengths were analyzed. Statistical analyses were performed using paired t
tests. RESULTS: The mean VAS score improved from 8.5 to 2.4 (P <.001). Nirschl
and Pettrone grades rated 43% (27 elbows) as excellent and 51% (32 elbows) as
good. The Mayo Elbow Performance scores improved from 72 to 88 (P <.001) and DASH
scores from 57 to 23 (P <.001). The mean grip strength of the affected side
improved from 30 to 43 lb (P <.001). The mean time required to return to work and
exercise was 2.8 months and 4.8 months, respectively. One case of heterotrophic
ossification, which had no functional instability afterward, was seen.
CONCLUSION: The results indicate that surgical treatment of medial epicondylitis
could be an effective and safe treatment when conservative treatment fails.
PMID- 27491572
TI - Erratum to "Genome-wide association study for rotator cuff tears identifies two
significant single-nucleotide polymorphisms" [J Shoulder Elbow Surg 2016;25:174
179].
PMID- 27491573
TI - Spontaneous Osteonecrosis of the Jaw During Bisphosphonate Therapy: An Unusual
Etiology of the Numb Chin Syndrome.
AB - The numb chin syndrome is a rare manifestation of intractable pain in the
palliative care setting and represents a major therapeutic challenge. The
reported etiologies of the numb chin syndrome include trauma, infections, immune
mediated systemic conditions, and malignancy, both through local infiltration or
compression of the inferior alveolar nerve sheath. The authors present the case
of a patient with long-standing multiple myeloma, suffering from numb chin
syndrome caused by a spontaneous osteonecrosis of the jaw after bisphosphonate
therapy. Intractable unilateral orofacial pain over the right chin and lower lip
with associated numbness and paresthesia in the distribution area of the mental
nerve were the clinical features. A complex pharmacological therapy, including
methadone, carbamazepine, and dexamethasone was started, with insufficient pain
control. In consideration of the prevalent neuropathic etiology, the authors
opted for a locoregional nerve block of the mandibular nerve with bupivacaine and
clonidine. The interdisciplinary approach was successful, and the patient was
discharged with satisfactory pain control. The purpose of this report is to
demonstrate the complexity of the therapeutic approach, which may include
pharmacological measures and interventional procedures to improve symptom
management in this challenging clinical condition.
PMID- 27491574
TI - Impact of physical activity and sedentarism on hydration status and liquid intake
in Spanish older adults. The PHYSMED study.
AB - INTRODUCTION: Data on hydration status in older adults are scarce and there are
very few studies focusing on the impact of physical activity (PA) on drinking
behavior. OBJECTIVE: To assess the impact of physical activity and sedentarism on
fluid intake in Spanish elderly. METHODS: 433 non-institutionalized Spanish older
adults (58% females), aged 55-88 years, volunteered for the PHYSMED study. PA
data were obtained by means of the Minnesota and EXERNET questionnaires.
Population was divided into four groups: ILS (inactive and low sedentary), IHS
(inactive and high sedentary), ALS (active and low sedentary) and AHS (active and
high sedentary). Serum from fasting blood samples was analysed for osmolarity.
RESULTS: The mean of total liquid intake was 1,751 +/- 628 mL/d. Significant
differences were observed for total liquid intake between ILS/ALS and IHS/ALS (p
< 0.001). ALS subjects consumed a higher amount of beverages such as water,
juice, milk, coffee, sport drink, beer, wine and distilled drinks than the other
PA groups. There was a significant difference for water intake between PA groups
(p < 0.01). Serum osmolarity values were within references ranges in all
subjects, and there was a signifi cant difference between PA groups (p < 0.01).
CONCLUSIONS: Spanish older adults meet the DACH recommendations set by the
German, Austrian and Swiss nutrition societies' liquid intake recommendations in
the mean independently of PA and sedentary level. All participants are within
reference ranges of serum osmolarity. Subjects in the active and low sedentary
group consumed higher amounts of water and other beverages than in the other PA
groups.
PMID- 27491575
TI - Nutritional differences in malnourished patients according to their liquid-intake
habits after hospital discharge.
AB - INTRODUCTION: Malnutrition is a serious and relatively common problem among
hospitalized patients; moreover, it is known that a good hydration state
contributes to health and wellbeing. OBJECTIVE: The aim of this study was to
determine the relationship between nutritional status, functional dependency,
quality of life and liquid-intake habits in malnourished patients after hospital
discharge. METHODS: Cross-sectional descriptive study in 91 patients (45 males)
who presented malnutrition at hospital discharge. The patients were grouped
according to their liquid intake estimated through the Mini Nutritional
Assessment questionnaire: 3-5 glasses (n = 42), and > 5 glasses (n = 46);
removing from analysis < 3 glasses of liquid intake (n = 3). The body mass index,
weight, Malnutrition Universal Screening Tool (MUST), functional dependency
(Barthel questionnaire), and quality of life (Short Form 12 Health Survey [SF
12]) were assessed 2-months after discharge. RESULTS: The > 5 glasses liquid
intake group showed better nutritional status than the 3-5 glasses intake group,
for weight (p < 0.001), body mass index (p = 0.001), and MUST scale (p = 0.020).
Additionally, the > 5 glasses liquid intake group signifi cantly scored higher
values in the total SF-12 questionnaire (p = 0.013), presenting better self
reported quality of life, and higher functional independency in the Barthel index
(p = 0.037) than the 3-5 glasses liquid intake group (p = 0.013). CONCLUSIONS:
Although further research is needed to elucidate the characteristics of this
relationship, descriptive comparisons between groups showed favorable nutritional
status, functional independency and quality of life for the > 5 glasses of liquid
intake compared with the 3-5 glasses of liquid intake group during a 2-months
follow-up.
PMID- 27491576
TI - Urinary hydration biomarkers and water sources in free-living elderly.
AB - INTRODUCTION: Accurate estimates of water intake and hydration status in
populations are essential to identify populations at risk of dehydration and
define strategies to improve standards of water intake. OBJECTIVE: To evaluate
the hydration status and the contribution of food and beverages to the total
water intake in a sample of free-living physically active Portuguese elderly.
METHODS: A sample of 74 individuals (28 men), aged 60 to 83 years, were included
in this study. A 24 h urine sample was collected; 24 h urine volume and
osmolality were quantifi ed in order to estimate the free water reserve (FWR)
used to assess the hydration status. A 24 h food recall corresponding to the day
of urine collection was obtained. Food and beverages were grouped according to
their nutritional composition, namely water content. The contribution of those
groups to total water intake and its association with the hydration status were
estimated. Urinary markers and food groups' contribution to total water intake
were compared between sexes and according to the median FWR, using the t-test and
Mann Whitney test. RESULTS: Less than 10% of the participants were classifi ed as
hypohydrated/at hypohydration risk. Water from food was nearly half of the total
water intake (47% in females and 48% in males, p = 0.757). "Water" (22%) and
"foods with reduced water content" (19%) were the groups that contributed the
most to the total water intake in women and men, respectively. In men, the
contribution of "alcoholic beverages" was signifi cantly higher than that of
women (10.5% vs 1.7%, p < 0.001). CONCLUSIONS: Even though most of the study
participants were classified as euhydrated, the contribution of water-rich and
nutritionally dense food, and non-alcoholic beverages, particularly in men,
should be promoted.
PMID- 27491577
TI - The association between water intake, body composition and cardiometabolic
factors among children - The Cuenca study.
AB - INTRODUCTION: Beverage consumption and its possible association with current
obesity epidemic and metabolic syndrome is under investigation in recent years,
however water intake is probably the most underestimated of all beverages and
could play an important role. OBJECTIVE: The aim of this study was to examine the
association between water intake, body composition and cardiometabolic factors in
a sample of Spanish children. METHODS: A cross-sectional study was conducted in
366 schoolchildren (53.5% girls) aged 9-11 years from the province of Cuenca in
Spain. Data of anthropometrics, body composition, cardiometabolic risk factors
and ardiorespiratory fi tness variables were collected. Beverage consumption was
assessed using two non-consecutive 24 h dietary recalls. RESULTS: We found an
inverse association between the consumption of water (ml)/kg per weight with BMI,
body fat, fat-free mass, waist circumference, insulin levels, HOMA-IR (p <
0.001), and with arterial pressure parameters, systolic (p < 0.010) and diastolic
blood pressure (p < 0.028), and mean arterial pressure (p < 0.012), as well as
direct associations with HDL cholesterol (p < 0.001). In ANCOVA analyses,
children who drank less water (ml)/kg per weight, had higher levels of LDL
cholesterol (p < 0.050) and lower levels of HDL cholesterol (p < 0.042), and
overweight-obesity subjects drank less water (ml)/kg per weight than normal peers
(p < 0.011). Besides, children with lower levels of HDL cholesterol and higher
levels of triglycerides and blood pressure had less water intake as a beverage.
Finally, children who drank less water from beverages had high levels of LDL
cholesterol. CONCLUSIONS: Higher consumption of water (ml)/kg per weight was
negatively associated with BMI, body fat, fat-free mass, waist circumference,
insulin levels, HOMA-IR, and positively with HDL cholesterol in children
independently of age, sex and cardiorespiratory fi tness. In addition, overweight
obese children drank less water (ml)/kg per weight than normoweight ones.
Therefore, water consumption is associated with numerous health benefi ts and its
adequate intake could contribute to prevent obesity and metabolic syndrome in
childhood.
PMID- 27491578
TI - Comparison of beverage consumption in adult populations from three different
countries: do the international reference values allow establishing the adequacy
of water and beverage intakes?
AB - INTRODUCTION: Recommendations of adequate total water intake (aTWI) have been
proposed by the European Food Safety Agency (EFSA) and the Institute of Medicine
(IOM)of the United States of America. However, there are differences in the
approach used to support them: IOM recommendation is based on average intakes
observed in NHANES III (Third National Health and Nutrition Examination Survey)
and EFSA recommendation on a combination of observed intakes from 13 different
European countries. Despite these recommendations of aTWI, the currently
available scientifi c evidence is not sufficient to establish a cut-off value
that would prevent disease, reduce the risk for chronic diseases or improve
health status. OBJECTIVE: To compare the average daily consumption of fluids
(water and other beverages) in selective samples of population from Mexico, US
and Spain, evaluating the quantity of fluid intake and understanding the
contribution of each fluid type to the total fl uid intake. We also aim to
determine if they reached adequate intake (AI) values, as defi ned by three
different criteria: IOM, EFSA and water density. METHODS: Three studies were
compared: from Mexico, the National Health and Nutrition Survey conducted in 2012
(NHNS 2012); from US, the NHANES III 2005-2010 and from Spain the ANIBES study
leaded in 2013. Different categories of beverages were used to establish the
pattern of energy intake for each country. Only adult population was selected.
TWI of each study was compared with EFSA and IOM AI recommendations, as well as
applying the criterion of water density (mL/kcal). RESULTS: The American study
obtained the higher value of total kcal/day from food and beverages (2,437 +/-
13). Furthermore, the percentage of daily energy intake coming from beverages
was, for American adults, 21%. Mexico was slightly behind with 19% and Spain
ANIBES study registered only 12%. ANIBES showed signifi cantly low AI values for
the overall population, but even more alarming in the case of males. Only 12% of
men, in contrast with 21% of women, do satisfy the EFSA criterion. The IOM
criterion reaches even less with higher recommended values for daily intake. In
contrast, 60% of the American population reached the recommended intake of the
IOM criterion. However, available data did not allow calculating the percentage
reached by the EFSA criterion. Data from the Mexican study did not permit
conducting comparisons with IOM or with EFSA. However, the water density criteria
(mL/kcal) was higher than 1. CONCLUSION: There is a notable difference between
all three populations in terms of TWI. Furthermore, within the same population,
values of adequacy of TWI changed signifi cantly when they were assessed using
different criteria. More scientifi c evidence is required for the production of
better defined water intake recommendations in the future as well as more studies
focusing on beverage consumption patterns in different settings.
PMID- 27491579
TI - Urinary hydration biomarkers and dietary intake in children.
AB - INTRODUCTION: The importance of hydration is undoubtable but reliable data on
hydration status and its relation with diet is lacking. OBJECTIVES: We aimed to
evaluate the hydration status and its relation to beverages and food intake in
children. METHODS: A sample of 172 (50% male), 7-11 year-old children was
included in this survey. Participants completed a 24 h urine collection; a 24
hours food recall corresponding to the day of urine collection was applied,
weight and height were measured and parents/caregivers fi lled a lifestyle and
socio-demographic questionnaire. The free water reserve was used to assess the
hydration status. The intakes of food and beverages were compared according to
hydration status using the t-test, Mann-Whitney test or unconditional regression
models as appropriate. RESULTS: More than half of the participants were classifi
ed as hypohydrated or at risk of hypohydration (57% in girls and 58% in boys).
Compared to hypohydrated children, a signifi cant higher consumption of water
(276.2 +/- 208.4 vs 188.2 +/- 187.4 g/day) and fruit juices (77.6 +/- 139.4 vs
14.4 +/- 57.2 g/day) was reported by euhydrated boys and girls, respectively.
Lower consumers of water and fruit juices showed a higher risk of hypohydration
(OR = 2.16, 95% CI: 1.02-4.58, p = 0.045), adjusting for confounders.
CONCLUSIONS: Most of the children included in this analysis were classifi ed as
at risk of hypohydration and those with higher water and fruit juices consumption
showed a better hydration status.
PMID- 27491580
TI - Dietary intake according to hydration status in 9-10 year-old soccer players.
AB - INTRODUCTION: Children have an increased risk of voluntary dehydration especially
during physical activity which may increase the risk of non-compensating water
losses. OBJECTIVES: The aim of this study was to assess the hydration status and
its relation to food intake in a children group of soccer players. METHOD: A
sample of 36 boys aged 9-10 years was included in this study; 30 completed a 24 h
urine collection. Participants completed a 24 h urine collection; a 24 hours food
recall corresponding to the day of urine collection was applied, weight and
height were measured and parents/caregivers fi lled a lifestyle and socio
demographic questionnaire. The free water reserve (FWR [ml/24 h] = urine volume
[ml/24 h] - obligatory urine volume [ml/24 h]) was used to assess the hydration
status. Food and beverage groups were created and models of unconditional
logistic regression were fi tted in order to estimate the magnitude of the
association between the hydration status and diet. RESULTS: Forty three per cent
of participants were classifi ed as at risk of hypohydration. Children who
reported a high fruit and vegetables intake (above the median) were at decreased
risk of hypohydration (OR = 0.19, 95% CI 0.04-0.94, p = 0.041), compared to
children who reported a low fruit and vegetables intake. CONCLUSIONS: Almost half
of the children were at risk of hypohydration. Our results suggested that water
food sources such as fruit and vegetables may contribute to euhydration.
PMID- 27491582
TI - Macronutrients contribution from beverages according to sex and age: findings
from the ANIBES Study in Spain.
AB - Methodologies and procedures used in dietary surveys have been widely developed
with the aim of evaluating the nutritional status of a population. However,
beverages are often either disregarded at national and international assessment
of nutrients intake or poorly mentioned. Moreover, there is no standardized
questionnaire developed as a research tool for the evaluation of beverages intake
in the general population. Moreover, the contribution of different beverages to
macronutrients intake is rarely provided. The latter in the context of a
continuous expansion and innovation of the beverages market in Spain. Therefore,
the main goal of the present study was to evaluate non-alcoholic and alcoholic
beverages macronutrients contribution in the ANIBES study in Spain (9-75 years
old).As expected, those contributed to dietary macronutrient intake mainly as
total carbohydrates and sugar. The contribution to other macronutrients (proteins
and lipids) by the beverage groups was of much less importance. For non-alcoholic
beverages, contribution to carbohydrates was much higher in younger populations
(children: 10.91 +/- 9.49%, mean +/- SD for boys and 9.46 +/- 8.83% for girls;
adolescents: 11.97 +/- 11.26% for men and 13.77 +/- 10.55% in women) than in
adults: 9.01 +/- 9.84% for men and 7.77 +/- 8.73% in women. Finally, a much lower
contribution was observed in the elderly: 4.22 +/- 6.10% for men and 4.46 +/-
6.56% for women. No sex differences, however, across all age groups were found.
Results for sugar contribution showed a similar trend: children (23.14 +/- 19.00%
for boys and 19.77 +/- 17.35% for girls); adolescents (28.13 +/- 24.17% for men
and 29.83 +/- 21.82% in women); adults 20.42 +/- 20.35% for men and 16.95 +/-
17.76% in women, p <= 0.01; and elderly: 14.63% +/- 9.97 for men and 9.33 +/-
12.86% in women. The main contribution corresponded to sugared soft drinks,
juices and nectars, more relevant and significant in the younger populations. As
for alcoholic beverages, the contribution of macronutrients to the total diet is
low for carbohydrates and sugar. The main contribution of this group, as
expected, is alcohol, being higher from low alcohol content beverages, and in men
vs women (p <= 0.001).
PMID- 27491581
TI - Fifty years of beverages consumption trends in Spanish households.
AB - OBJECTIVES: To describe the evolution of non-alcoholic and alcoholic beverages
consumption in the Spanish households from the 60's to nowadays. METHODS: This
study is based on beverages and food consumption in Spanish households; the data
sample consisted of consumption and distribution data, obtained from the
Household Budget Survey (HBS) since 1964 to 1991 and from the Food Consumption
Survey (FCS) since 2000 to 2014, in collaboration with the Spanish Nutrition
Foundation (FEN). RESULTS: In 2014 the average consumption of non-alcoholic
beverages was 332 g/person/day, whereas alcoholic beverages consumption
represented 72.6 g/person/day. Consumption of non-alcoholic beverages has
increased 721% (1964: 46 g/person/day; 1991: 96 g/person/day; 2000: 240
g/person/day and 2014: 332 g/person/day), whereas alcoholic beverages consumption
has decreased roughly a 50% (1964: 145 g/person/day; 1991: 113 g/person/day;
2000: 78.4 g/person/day and 2014: 72.6 g/person/day). The most consumed alcoholic
beverage in 2014 was beer (41.3 g/day), followed by wine (23.0 g/day). Regarding
non-alcoholic beverages, the most consumed was water (144 g/day), followed by
cola (ordinary: 30.7 g/day and diet: 20.5 g/day).According to Spanish regions, in
2014 non-alcoholic beverages were the most consumed in the islands (Balearic
Islands 521 grams/person/day; Canary Islands 515 grams/person/day), as it was in
the nineties (Balearic Islands 148 grams/person/day and Canary Islands 281
grams/person/day). However in 1980-81 the largest consumption of alcoholic
beverages was that of Galicia, 408 g/person per day, and the lower in the Canary
Islands, 63 g/person per day. In 2014, Murcia and Andalucia represented the
regions with the highest consumption of alcoholic beverages. In 2014, alcoholic
beverages provided roughly 1.89% of the total energy and 1.47% of sugars, whereas
non-alcoholic beverages provided 3.28% of energy and 15.72% of sugars and, in
2000, alcoholic beverages contributed 2.29% of the energy and 1.47% of sugars and
non-alcoholic drinks provided 3.76% of the energy and 22.7% of sugars.
CONCLUSION: There have been signifi cant changes in the eating patterns at the
Spanish homes, especially regarding beverages consumption, over the last five
decades. In general, a higher consumption and variety for non-alcoholic drinks
has occurred, especially in the islands. In parallel, a decline in alcoholic
beverages consumption has been clearly observed.
PMID- 27491583
TI - Effects of maternal hydration status on the osmolality of maternal milk.
AB - BACKGROUND: It has been demonstrated that human milk osmolality (Mosm) is
regulated within an established range, typically 290 to 300 mOsm/kg, and appears
to be resistant to effects of maternal dehydration, as refl ected by high urinary
osmolality (Uosm). OBJECTIVE: To determine the degree of association between Mosm
and Uosm at a common point in time, as well as the reproducibility of both
measures over a one-week interval of sampling. METHODS: Mosm and Uosm were
measured with a Vogel Loser 450 osmometer on samples of the respective biological
fluids collected concurrently in 31 lactating women, with infants aged between 30
and 340 days. In the first 15 women recruited, collections were repeated 7 days
after the initial ones. RESULTS: The median Mosm for the 46 samples collected was
308 mOsm/kg with a range from 288 to 448 mOsm/kg. The corresponding values for
Uosm were 598 mOsm/kg with a range from 93 to 1,678 mOsm/kg. The Spearman rank
order correlation coeffi cient for within-individual association of Mosm and Uosm
was r = 0.214 (p = 0.153). The median Mosm for the 15 repeat-subjects was 309
mOsm/kg on both occasions, with a within-individual Spearman coeffi cient of r =
0.326 (p = 0.118). By contrast, for the Uosm, the within-subject association was
much stronger, with r = 0.699 (p = 0.002). CONCLUSIONS: The osmometry technique
proved to be a highly stable and reproducible measurement technique. Mosm and
Uosm are not significantly associated at a point in time. Intra-subject Mosm
varies more across time than intra-subject Uosm.
PMID- 27491584
TI - A new educational tool to learn about hydration: taste workshops for children.
AB - INTRODUCTION: Nutrition education contributes to children's understanding and
practice of healthy lifestyles behaviors. Having a well hydration status is an
essential topic, especially since children are a vulnerable population who are
much more prone to dehydration than adults are. The approval of the Report on
the European Gastronomic Heritage: Cultural and Educational Aspects in 2014
served as starting point to work on innovative audio-visual and multimedia
materials for children. The Spanish Nutrition Foundation (FEN) and the Royal
Academy of Gastronomy (RAG), in collaboration with the Ministry of Education,
Culture and Sport in Spain (MECD), developed educational videos for
schoolchildren to learn about food, nutrition and gastronomy, specially, the
importance of being hydrated. OBJECTIVES: To develop a serial of videos for
children between 3 and 9 years old with nutrition and cooking lessons to be used
as educational resources in the official curricula. METHODS: Fourteen chapters
related to food, nutrition, gastronomy, physical activity and hydration to be
used to record videos were designed and tested. A nutritionist, a chef and two
puppets were the main characters acting in the videos. RESULTS: The chapters
were assembled in nine videos that included five sections: introduction, video
lesson, recipes -in case of hydration, recipes with different water content foods
were recorded-, what have you learntand check your knowledge. A summary of the
new educational material was officially presented at the Spain Pavilion during
the Expo Milano 2015. Moreover, they are included as education tool for teachers
in the new PANGEI Programme (Food, Nutrition and Gastronomy for Infantile
Education) conjointly launched by FEN, RAG and MEDC. CONCLUSION: Taste workshops
are useful as innovative nutrition education tools to reinforce language,
listening and motor skills as well as food and nutrition concepts, and specially,
the importance of being well hydrated.
PMID- 27491585
TI - The use of moderated mediated analysis to study the influence of hypo-hydration
on working memory.
AB - INTRODUCTION: To date, dehydration has been typically reported to infl uence
psychological parameters when there has been at least a 2% loss of body mass,
although there has been little examination of those going about their everyday
lives, those who have lost less than 1% of body mass. In such situations factors
such as the initial hydration status and individual differences in the response
to a reduced fl uid intake are likely to be infl uential. Yet to study the
complexity added by such additional variables novel methods of statistical
analysis are required. OBJECTIVES: The present study describes the use of
moderated mediation, an approach that asks various questions: fi rstly, is
drinking infl uential?; secondly, does a mediator (e.g.,thirst) sit between an
independent and dependent variable?; and thirdly, does an effect only occur under
certain conditions such as initial osmolality? METHOD: In the study, 118 subjects
were exposed to 30 degrees C for four hours during which they half drank 300 ml
water. The serial sevens test of working memory was performed before and at the
end of the procedure. RESULTS: A 0.6% loss of body mass reduced the effi ciency
of working memory. Those who consumed water had better working memory; working
memory was worse in participants who lost more body mass or became thirstier, but
only in those with higher levels of baseline osmolality. CONCLUSIONS: Small
variations in hydration status infl uenced cognitive functioning although there
were individual differences in the response. The parameters that influence an
adverse response to hypo-hydration need to be established to allow giving
appropriate advice.
PMID- 27491586
TI - Frailty and sarcopenia: From theory to clinical implementation and public health
relevance.
AB - The sustainability of healthcare systems is threatened by the increasing
(absolute and relative) number of older persons referring to clinical services.
Such global phenomenon is questioning the traditional paradigms of medicine,
pushing towards the need of new criteria at the basis of clinical decision
algorithms. In this context, frailty has been advocated as a geriatric condition
potentially capable of overcoming the weakness of chronological age in the
identification of individuals requiring adapted care due to their increased
vulnerability to stressors. Interestingly, frailty poses itself beyond the
concept of nosological conditions due to the difficulties at correctly framing
traditional diseases in the complex and heterogeneous scenario of elders. Thus,
frailty may play a key role in public health policies for promoting integrated
care towards biologically aged individuals, currently presenting multiple unmet
clinical needs. At the same time, the term frailty has also been frequently used
in the literature for framing a physical condition of risk for (mainly
functional) negative endpoints. The combination of such physical impairment with
an organ-specific phenotype (e.g., the age-related skeletal muscle decline or
sarcopenia) may determine the assumptions for the development of a clinical
condition to be used as potential target for ad hoc interventions against
physical disability. In the present article, we present the background of frailty
and sarcopenia, and discuss their potentialities for reshaping current clinical
and research practice in order to promote holistic approach to older patients,
solicit personalization of care, and develop new targets for innovative
interventions.
PMID- 27491588
TI - The beneficial effect of acute phase increase in serum ferritin.
PMID- 27491587
TI - Validation of PROFUND prognostic index over a four-year follow-up period.
AB - BACKGROUND/OBJECTIVES: The PROFUND index stratifies accurately the 12-month
mortality risk of polypathological patients (PPs), but its fitness over a longer
follow-up period remains unknown. We aimed to explore the calibration and
discrimination power of PROFUND index over 4-years, in order to assess its follow
up interval generalizability. DESIGN: Multicenter prospective cohort-study.
SETTING: 33 Spanish hospitals. PARTICIPANTS: PPs included after hospital
discharge, outpatient clinics, or home hospitalization. MEASUREMENTS: Mortality
over a 4-year follow-up period. METHODS: PROFUND index calibration was assessed
by risk-quartiles predicted/observed mortality (Hosmer-Lemeshow goodness-of-fit
test), and its discrimination power by ROC curves. RESULTS: A total of 768
patients were included (630 [82%] of them completed the 4-year follow-up). Global
mortality rate was 63.5%. When assessing individual patient scores, mortality was
52% in the lowest risk group (0-2 points in PROFUND score); 73.5% in the low
intermediate risk group (3-6 points), 85% in the intermediate-high group (7-10
points); and 92% in the highest risk group (>=11 points). Accuracy testing of the
PROFUND index showed good calibration (P=.8 in the Hosmer-Lemeshow goodness-of
fit test), and also a good discrimination power (AUC=0.71 [0.67-0.77] in ROC
curve). CONCLUSIONS: The PROFUND index maintained its accuracy in predicting
mortality of polypathological patients over a 4-year follow-up period. This index
may be of potential usefulness in deciding the most appropriate health-care
interventions in populations with multimorbidity.
PMID- 27491589
TI - Nicotinic receptor blockade decreases fos immunoreactivity within
orexin/hypocretin-expressing neurons of nicotine-exposed rats.
AB - Tobacco smoking is the leading cause of preventable death in the United States.
Nicotine is the principal psychoactive ingredient in tobacco that causes
addiction. The structures governing nicotine addiction, including those
underlying withdrawal, are still being explored. Nicotine withdrawal is
characterized by negative affective and cognitive symptoms that enhance relapse
susceptibility, and suppressed dopaminergic transmission from ventral tegmental
area (VTA) to target structures underlies behavioral symptoms of nicotine
withdrawal. Agonist and partial agonist therapies help 1 in 4 treatment-seeking
smokers at one-year post-cessation, and new targets are needed to more
effectively aid smokers attempting to quit. Hypothalamic orexin/hypocretin
neurons send excitatory projections to dopamine (DA)-producing neurons of VTA and
modulate mesoaccumbal DA release. The effects of nicotinic receptor blockade,
which is commonly used to precipitate withdrawal, on orexin neurons remain poorly
investigated and present an attractive target for intervention. The present study
sought to investigate the effects of nicotinic receptor blockade on hypothalamic
orexin neurons using mecamylamine to precipitate withdrawal in rats. Separate
groups of rats were treated with either chronic nicotine or saline for 7-days at
which point effects of mecamylamine or saline on somatic signs and anxiety-like
behavior were assessed. Finally, tissue from rats was harvested for
immunofluorescent analysis of Fos within orexin neurons. Results demonstrate that
nicotinic receptor blockade leads to reduced orexin cell activity, as indicated
by lowered Fos-immunoreactivity, and suggest that this underlying cellular
activity may be associated with symptoms of nicotine withdrawal as effects were
most prominently observed in rats given chronic nicotine. We conclude from this
study that orexin transmission becomes suppressed in rats upon nicotinic receptor
blockade, and that behavioral symptoms associated with nicotine withdrawal may be
aided by intervention upon orexinergic transmission.
PMID- 27491590
TI - Behavioral deficits induced by third-trimester equivalent alcohol exposure in
male C57BL/6J mice are not associated with reduced adult hippocampal neurogenesis
but are still rescued with voluntary exercise.
AB - Prenatal alcohol exposure can produce permanent alterations in brain structure
and profound behavioral deficits. Mouse models can help discover mechanisms and
identify potentially useful interventions. This study examined long-term
influences of either a single or repeated alcohol exposure during the third
trimester equivalent on survival of new neurons in the hippocampus, behavioral
performance on the Passive avoidance and Rotarod tasks, and the potential role of
exercise as a therapeutic intervention. C57BL/6J male mice received either saline
or 5g/kg ethanol split into two s.c. injections, two hours apart, on postnatal
day (PD)7 (Experiment 1) or on PD5, 7 and 9 (Experiment 2). All mice were weaned
on PD21 and received either a running wheel or remained sedentary from PD35
PD80/81. From PD36-45, mice received i.p. injections of 50mg/kg bromodeoxyuridine
(BrdU) to label dividing cells. Behavioral testing occurred between PD72-79.
Number of surviving BrdU+ cells and immature neurons (doublecortin; DCX+) was
measured at PD80-81. Alcohol did not affect number of BrdU+ or DCX+ cells in
either experiment. Running significantly increased number of BrdU+ and DCX+ cells
in both treatment groups. Alcohol-induced deficits on Rotarod performance and
acquisition of the Passive avoidance task (Day 1) were evident only in Experiment
2 and running rescued these deficits. These data suggest neonatal alcohol
exposure does not result in long-term impairments in adult hippocampal
neurogenesis in the mouse model. Three doses of ethanol were necessary to induce
behavioral deficits. Finally, the mechanisms by which exercise ameliorated the
neonatal alcohol induced behavioral deficits remain unknown.
PMID- 27491591
TI - Functional brain networks underlying latent inhibition of conditioned disgust in
rats.
AB - The present experiment examined the neuronal networks involved in the latent
inhibition of conditioned disgust by measuring brain oxidative metabolism. Rats
were given nonreinforced intraoral (IO) exposure to saccharin (exposed groups) or
water (non-exposed groups) followed by a conditioning trial in which the animals
received an infusion of saccharin paired (or unpaired) with LiCl. On testing,
taste reactivity responses displayed by the rats during the infusion of the
saccharin were examined. Behavioral data showed that preexposure to saccharin
attenuated the development of LiCl-induced conditioned disgust reactions,
indicating that the effects of taste aversion on hedonic taste reactivity had
been reduced. With respect to cumulative oxidative metabolic activity across the
whole study period, the parabrachial nucleus was the only single region examined
which showed differential activity between groups which received saccharin-LiCl
pairings with and without prior non-reinforced saccharin exposure, suggesting a
key role in the effects of latent inhibition of taste aversion learning. In
addition, many functional connections between brain regions were revealed through
correlational analysis of metabolic activity, in particular an accumbens-amygdala
interaction that may be involved in both positive and negative hedonic responses.
PMID- 27491592
TI - Self-testing for Trichomonas vaginalis at home using a point-of-care test by
women who request kits via the Internet.
AB - We offered a point-of-care test for Trichomonas vaginalis to women via the
Internet to determine if it was acceptable to women to perform the test at home.
Most of the 102 participants felt that it was easy to collect the specimen,
follow the instructions, and read and interpret the results for the trichomonas
self-testing assay.
PMID- 27491593
TI - Additive effects of levonorgestrel and ethinylestradiol on brain aromatase
(cyp19a1b) in zebrafish specific in vitro and in vivo bioassays.
AB - Estrogens and progestins are widely used in combination in human medicine and
both are present in aquatic environment. Despite the joint exposure of aquatic
wildlife to estrogens and progestins, very little information is available on
their combined effects. In the present study we investigated the effect of
ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the
expression of the brain specific ER-regulated cyp19a1b gene. For that purpose,
recently established zebrafish-derived tools were used: (i) an in vitro transient
reporter gene assay in a human glial cell line (U251-MG) co-transfected with
zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of
the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a
transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b
gene promoter (cyp19a1b-GFP). Concentration-response relationships for single
chemicals were modeled and used to design the mixture experiments following a ray
design. The results from mixture experiments were analyzed to predict joint
effects according to concentration addition and statistical approaches were used
to characterize the potential interactions between the components of the mixtures
(synergism/antagonism). We confirmed that some progestins could elicit estrogenic
effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic
effects both in vitro and in vivo, suggesting that some environmental progestin
could exert effects that will add to those of environmental (xeno-)estrogens.
Moreover, our zebrafish specific assays are valuable tools that could be used in
risk assessment for both single chemicals and their mixtures.
PMID- 27491594
TI - Comparative Evaluation of Four Risk Scores for Predicting Mortality in Patients
With Implantable Cardioverter-defibrillator for Primary Prevention.
AB - INTRODUCTION AND OBJECTIVES: Several clinical risk scores have been developed to
identify patients at high risk of all-cause mortality despite implantation of an
implantable cardioverter-defibrillator. We aimed to examine and compare the
predictive capacity of 4 simple scoring systems (MADIT-II, FADES, PACE and
SHOCKED) for predicting mortality after defibrillator implantation for primary
prevention of sudden cardiac death in a Mediterranean country. METHODS: A
multicenter retrospective study was performed in 15 Spanish hospitals.
Consecutive patients referred for defibrillator implantation between January 2010
and December 2011 were included. RESULTS: A total of 916 patients with ischemic
and nonischemic heart disease were included (mean age, 62 +/- 11 years, 81.4%
male). Over 33.4 +/- 12.9 months, 113 (12.3%) patients died (cardiovascular
origin in 86 [9.4%] patients). At 12, 24, 36, and 48 months, mortality rates were
4.5%, 7.6%, 10.8%, and 12.3% respectively. All the risk scores showed a stepwise
increase in the risk of death throughout the scoring system of each of the scores
and all 4 scores identified patients at greater risk of mortality. The scores
were significantly associated with all-cause mortality throughout the follow-up
period. PACE displayed the lowest c-index value regardless of whether the
population had heart disease of ischemic (c-statistic = 0.61) or nonischemic
origin (c-statistic = 0.61), whereas MADIT-II (c-statistic = 0.67 and 0.65 in
ischemic and nonischemic cardiomyopathy, respectively), SHOCKED (c-statistic =
0.68 and 0.66, respectively), and FADES (c-statistic = 0.66 and 0.60) provided
similar c-statistic values (P >= .09). CONCLUSIONS: In this nontrial-based cohort
of Mediterranean patients, the 4 evaluated risk scores showed a significant
stepwise increase in the risk of death. Among the currently available risk
scores, MADIT-II, FADES, and SHOCKED provide slightly better performance than
PACE.
PMID- 27491596
TI - A Highly Chemically Stable Metal-Organic Framework as a Luminescent Probe for the
Regenerable Ratiometric Sensing of pH.
AB - A heteroatom-rich 3D noninterpenetrating metal-organic framework (MOF) Cd-EDDA
constructed from an ethylene glycol ether bridging tetracarboxylate ligand H4
EDDA (5,5'-(ethane-1,2-diylbis(oxy))diisophthalic acid) shows good chemical
resistance to both acidic and alkaline solutions with a pH ranging from 2.0 to
12.2. There is a corresponding ratiometric luminescence response to pH from 2.0
to 11.5, and the sensing mechanism is also discussed through ion chromatography
and molecular force field-based calculations. Importantly, the probe can easily
be regenerated simply by modulating the pH of the solution, thus being the first
example of a regenerable MOF-based ratiometric luminescent probe for pH.
PMID- 27491595
TI - Ulnar Distraction Osteogenesis in the Treatment of Forearm Deformities in
Children With Multiple Hereditary Exostoses.
AB - PURPOSE: To report on the outcomes of using ulnar lengthening combined with acute
angular correction for the treatment of forearm deformities in patients affected
by multiple hereditary exostoses (MHE). Our hypothesis was that this procedure
would improve both radiographic measurements and clinical outcomes with minimal
complications. METHODS: A retrospective chart review was performed on patients
who had a diagnosis of MHE and had undergone ulnar lengthening via a uniplanar
external fixator over a 12-year period. Clinical outcomes such as range of
motion, pain, and surgical complications were assessed. Radiographic changes were
measured using interval radiographs. RESULTS: The series included 17 patients.
Median age at surgery was 7 years (range, 3-14 years). Median follow up was 55
months (range, 5-125 months). Improvements occurred in radial and ulnar radii of
curvature, carpal slip, ulnar variance, and carrying angle at the elbow. There
was 1 major pin track infection. There were 2 failures of the external fixator
requiring exchange. Premature consolidation occurred in 1 case. Elbow, forearm,
and wrist motion was not affected. Radiocapitellar joint congruency did not
change. No patient reported pain at final follow-up. CONCLUSIONS: Our approach of
using distraction osteogenesis of the ulna with angular correction in the radius
and ulna as needed is able to correct carpal slip as well as to improve forearm
bowing and elbow carrying angle. All of the patients maintained congruency of the
radiocapitellar joint with no postoperative dislocations. Because of the low
complication rate, the resolution of pain in patients who presented with pain,
and the improvement of forearm bowing, this approach should be considered as a
treatment option for children with MHE who are at risk for radiocapitellar
dislocation. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
PMID- 27491597
TI - Dressed active particles in spherical crystals.
AB - We investigate the dynamics of an active particle in two-dimensional spherical
crystals, which provide an ideal environment to illustrate the interplay between
active particles and crystallographic defects. A moving active particle is
observed to be surrounded by localized topological defects, becoming a dressed
active particle. Such a physical picture characterizes both the lattice
distortion around the moving particle and the healing of the distorted lattice in
its trajectory. We find that the dynamical behaviors of an active particle in
both random and ballistic motions uniformly conform to this featured scenario,
whether the particle is initially a defect or not. We further observe that the
defect pattern around a dressed ballistic active particle randomly oscillates
between two well-defined wing-like defect motifs regardless of its speed. The
established physical picture of dressed active particles in this work partially
deciphers the complexity of the intriguing nonequilibrium behaviors in active
crystals, and opens the promising possibility of introducing the activity to
engineer defects, which has strong connections with the design of materials.
PMID- 27491598
TI - Using Laser-Induced Thermal Voxels to Pattern Diverse Materials at the Solid
Liquid Interface.
AB - We describe a high-resolution patterning approach that combines the spatial
control inherent to laser direct writing with the versatility of benchtop
chemical synthesis. By taking advantage of the steep thermal gradient that occurs
while laser heating a metal edge in contact with solution, diverse materials
comprising transition metals are patterned with feature size resolution nearing 1
MUm. We demonstrate fabrication of reduced metallic nickel in one step and
examine electrical properties and air stability through direct-write integration
onto a device platform. This strategy expands the chemistries and materials that
can be used in combination with laser direct writing.
PMID- 27491599
TI - Corrigendum to "Bluetongue virus surveillance in the Islamic Republic of
Mauritania: Is serotype 26 circulating among cattle and dromedaries?" [Infect.
Genet. Evol. (2016) 40:109-112].
PMID- 27491600
TI - Hepato-preferential insulins: Is this the end, or the end of the beginning?
PMID- 27491601
TI - Combined Use of Bivalirudin and Radial Access in Acute Coronary Syndromes Is Not
Superior to the Use of Either One Separately: Meta-Analysis of Randomized
Controlled Trials.
AB - OBJECTIVES: The aim of this meta-analysis was to study the relation between
access site and bivalirudin use on outcomes in patients with acute coronary
syndrome (ACS). BACKGROUND: Bivalirudin and radial access use are 2 strategies
that are increasingly used to lower major bleeding in patients with ACS
undergoing invasive approaches. The interaction between these 2 strategies and
the benefit of using them in combination are unclear. METHODS: This analysis
included randomized controlled trials that compared bivalirudin to heparin with
or without glycoprotein IIb/IIIa inhibitors in patients with ACS and reported
outcomes stratified by arterial access site. Meta-analyses of outcome data were
performed on the basis of access site and anticoagulation regimen. Pooled odds
ratios (ORs) and 95% confidence intervals (CIs) were calculated from event rates
using random-effects models. RESULTS: Eight trials with a total of 27,491
patients were included. Bivalirudin reduced major bleeding risk in patients with
femoral access (OR: 0.51; 95% CI: 0.46 to 0.6; p < 0.001) but not in patients
with radial access (OR: 0.75; 95% CI: 0.45 to 1.26; p = 0.28). Moreover, radial
access reduced major bleeding risk in patients treated with heparin (OR: 0.57;
95% CI: 0.43 to 0.77; p < 0.001) but not in patients treated with bivalirudin
(OR: 0.96; 95% CI: 0.65 to 1.41; p = 0.83). There were no differences in major
adverse cardiovascular events or all-cause mortality between bivalirudin and
heparin, regardless of access site. CONCLUSIONS: Bivalirudin reduces bleeding
risk only with femoral access, and radial access reduces bleeding risk only with
heparin anticoagulation. Therefore, there is no additional benefit to the
combined use of bivalirudin and radial access strategies in patients with ACS.
PMID- 27491602
TI - The Fuzzy Math of Anticoagulation and Access Site: When 1 + 1 Does Not Always
Equal 2.
PMID- 27491603
TI - Prognostic Impact of Chronic Total Occlusions: A Report From SCAAR (Swedish
Coronary Angiography and Angioplasty Registry).
AB - OBJECTIVES: The aim of this study was to determine the prognostic impact of
chronic total occlusion (CTO) on long-term mortality in a large prospective
cohort. BACKGROUND: CTO is present in many patients with coronary artery disease
and is difficult to treat with percutaneous coronary intervention. METHODS: The
study population consisted of all consecutive patients who underwent coronary
angiography in Sweden between January 1, 2005 and January 1, 2012, who were
registered in SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The
patient population was heterogeneous with regard to indication for angiography
(stable angina, ST-segment elevation myocardial infarction [STEMI], unstable
angina or non-STEMI, and other) and treatment options. The long-term mortality
rates of patients with and without CTO were compared by using shared frailty Cox
proportional hazards regression adjusted for confounders. Tests were conducted
for interactions between CTO and several pre-specified characteristics:
indication for angiography and percutaneous coronary intervention (stable angina,
STEMI, unstable angina or non-STEMI, and other), severity of coronary artery
disease (1-, 2-, and 3-vessel and/or left main coronary artery disease), age,
sex, and diabetes. RESULTS: During the study period, 14,441 patients with CTO and
75,431 patients without CTO were registered in SCAAR. CTO was associated with
higher mortality (hazard ratio: 1.29; 95% confidence interval: 1.22 to 1.37; p <
0.001). In subgroup analyses, the risk attributable to CTO was lowest in patients
with stable angina and highest in those with STEMI. In addition, CTO was
associated with highest risk in patients under 60 years of age and with lowest
risk in octogenarians. There was no interaction between CTO and either diabetes
or sex, suggesting an equally adverse effect in both groups. CONCLUSIONS: In this
large prospective observational study of patients with coronary artery disease,
CTO was associated with increased mortality. This association was most prominent
in younger patients and in those with acute coronary syndromes.
PMID- 27491604
TI - Chronic Total Coronary Occlusions, Percutaneous Coronary Intervention, and
Mortality: A "Hybrid Approach" to Interpretation.
PMID- 27491605
TI - Individual Long-Term Mortality Prediction Following Either Coronary Stenting or
Bypass Surgery in Patients With Multivessel and/or Unprotected Left Main Disease:
An External Validation of the SYNTAX Score II Model in the 1,480 Patients of the
BEST and PRECOMBAT Randomized Controlled Trials.
AB - OBJECTIVES: The study sought to validate the SYNTAX (Synergy Between Percutaneous
Coronary Intervention With Taxus and Cardiac Surgery) score II mortality
prediction model after percutaneous coronary intervention (PCI) or coronary
artery bypass grafting in a large pooled population of patients with multivessel
coronary disease (MVD) and/or unprotected left main disease (UPLMD) enrolled in
the PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in
Patients With Left Main Coronary Artery Disease) and BEST (Artery Bypass Surgery
and Everolimus-Eluting Stent Implantation in the Treatment of Patients with
Multivessel Coronary Artery Disease) randomized controlled trials. BACKGROUND:
For patients with MVD and/or UPLMD, the choice of the best revascularization
strategy remains challenging. METHODS: Pooled individual patient-level data from
PRECOMBAT and BEST were used to assess calibration and discrimination of the
SYNTAX score II prediction model for all-cause mortality after PCI and coronary
artery bypass grafting at 4-year follow-up. The study population comprised 1,480
patients (600 with UPLMD, 880 with MVD). RESULTS: The overall incidence of all
cause mortality was 6.1% after a median follow-up period of 4.9 years. Validation
plots showed good model calibration overall and across treatment groups but
tended to overestimate all-cause mortality in the highest risk quintiles of
patients in the whole population and the PCI arm. The SYNTAX score II showed
moderate discrimination ability for the whole population (C index = 0.685) but
better for patients receiving PCI than CABG (C index = 0.718 vs. 0.662 in
patients with UPLMD, C index = 0.700 vs. 0.661 in those with MVD). Observed all
cause mortality was higher when the treatment received was at variance with that
recommended by the model and similar when it was concordant. CONCLUSIONS: The
SYNTAX score II has good calibration but only moderate discrimination ability for
long-term mortality prediction in this randomized population. This score provides
an important tool to help guide the heart team's decision-making process
regarding the selection of the best revascularization strategy for patients with
MVD and/or UPLMD. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting
Stent in Patients With Left Main Coronary Artery Disease, NCT00422968; Bypass
Surgery Versus Everolimus-Eluting Stent Implantation for Multivessel Coronary
Artery Disease, NCT00997828).
PMID- 27491606
TI - Coronary Revascularization: How Can Model-Derived Probabilities Inform Clinical
Judgment?
PMID- 27491608
TI - Harnessing the Potential of Human Autologous Stem Cells to Treat Refractory
Angina.
PMID- 27491607
TI - The RENEW Trial: Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell
Administration in Patients With Refractory Angina.
AB - OBJECTIVES: This study tested whether intramyocardial (IM) administration of
mobilized, purified autologous CD34(+) cells would improve total exercise time
(TET) and angina frequency in patients with refractory angina. BACKGROUND: IM
administration of autologous CD34(+) cells has been associated consistently with
improvements in functional capacity and angina symptoms in early phase clinical
trials. METHODS: RENEW (Efficacy and Safety of Targeted Intramyocardial Delivery
of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With
Refractory Angina) was a randomized, double-blind, multicenter trial comparing IM
CD34(+) administration with no intervention (open-label standard of care) or IM
placebo injections (active control). The primary efficacy endpoint was change in
TET at 12 months. Key secondary endpoints include changes in angina frequency at
3, 6, and 12 months, and TET at 3 and 6 months. The key safety analysis was the
incidence of major adverse cardiovascular events through 24 months. RESULTS: The
sponsor terminated the study for strategic considerations after enrollment of 112
of planned 444 patients. The difference in TET between patients treated with cell
therapy versus placebo was 61.0 s at 3 months (95% confidence interval (CI): -2.9
to 124.8; p = 0.06), 46.2 s at 6 months (95% CI: -28.0 to 120.4; p = 0.22), and
36.6 s at 12 months (95% CI: -56.1 to 129.2; p = 0.43); angina frequency was
improved at 6 months (relative risk: 0.63; p = 0.05). Autologous CD34(+) cell
therapy seemed to be safe compared with both open-label standard of care and
active control (major adverse cardiovascular events 67.9% [standard of care],
42.9% (active control), 46.0% [CD34(+)]). CONCLUSIONS: Due to early termination,
RENEW was an incomplete experiment; however, the results were consistent with
observations from earlier phase studies. These findings underscore the need for a
definitive trial. (Efficacy and Safety of Targeted Intramyocardial Delivery of
Auto CD34(+) Stem Cells for Improving Exercise Capacity in Subjects With
Refractory Angina [RENEW]: NCT01508910).
PMID- 27491610
TI - Examining Female-Specific Factors Lends Insight Into Women's More Favorable
Prognosis in Transcatheter Aortic Valve Replacement.
PMID- 27491609
TI - Acute and 30-Day Outcomes in Women After TAVR: Results From the WIN-TAVI (Women's
INternational Transcatheter Aortic Valve Implantation) Real-World Registry.
AB - OBJECTIVES: The study sought to examine the safety and performance of
transcatheter aortic valve replacement (TAVR) using an all-female registry and to
further explore the potential impact of female sex-specific characteristics on
clinical outcomes after TAVR. BACKGROUND: Although women comprise 50% of patients
with symptomatic severe aortic stenosis undergoing TAVR, the optimal treatment
strategy remains undetermined. METHODS: The WIN-TAVI (Women's INternational
Transcatheter Aortic Valve Implantation) registry is a multinational,
prospective, observational registry of women undergoing TAVR for aortic stenosis,
conducted without any external funding. The primary endpoint was the Valve
Academic Research Consortium (VARC)-2 early safety endpoint at 30 days (composite
of mortality, stroke, major vascular complication, life-threatening bleeding,
stage 2 or 3 acute kidney injury, coronary artery obstruction, or repeat
procedure for valve-related dysfunction). RESULTS: Between January 2013 and
December 2015, 1,019 women were enrolled across 19 European and North American
centers. The mean patient age was 82.5 +/- 6.3 years, mean EuroSCORE I was 17.8
+/- 11.7% and mean Society of Thoracic Surgeons score was 8.3 +/- 7.4%. TAVR was
performed via transfemoral access in 90.6% and new-generation devices were used
in 42.1%. In more than two-thirds of cases, an Edwards SAPIEN 23 mm (Edwards
Lifesciences, Irvine, California) or Medtronic CoreValve <=26 mm (Medtronic Inc.,
Minneapolis, Minnesota) device was implanted. The 30-day VARC-2 composite
endpoint occurred in 14.0% with 3.4% all-cause mortality, 1.3% stroke, 7.7% major
vascular complications, and 4.4% VARC life-threatening bleeding. The independent
predictors of the primary endpoint were age (odds ratio [OR]: 1.04; 95%
confidence interval [CI]: 1.00 to 1.08), prior stroke (OR: 2.02; 95% CI: 1.07 to
3.80), left ventricular ejection fraction <30% (OR: 2.62; 95% CI: 1.07 to 6.40),
new device generation (OR: 0.59; 95% CI: 0.38 to 0.91), and history of pregnancy
(OR: 0.57; 95% CI: 0.37 to 0.85). CONCLUSIONS: Women enrolled in this first ever
all-female TAVR registry with collection of female sex-specific baseline
parameters, were at intermediate-high risk and experienced a 30-day VARC-2
composite safety endpoint of 14.0% with a low incidence of early mortality and
stroke. Randomized assessment of TAVR versus surgical aortic valve replacement in
intermediate risk women is warranted to determine the optimal strategy.
PMID- 27491612
TI - When Transcatheter Aortic Valve Replacement Is Not Enough: A Step Toward
Understanding When Concomitant Mitral Regurgitation Needs Treatment.
PMID- 27491611
TI - Mitral Regurgitation After Transcatheter Aortic Valve Replacement: Prognosis,
Imaging Predictors, and Potential Management.
AB - OBJECTIVES: This study sought to analyze the clinical impact of the degree and
improvement of mitral regurgitation in TAVR recipients, validate the main imaging
determinants of this improvement, and assess the potential candidates for double
valve repair with percutaneous techniques. BACKGROUND: Many patients with severe
aortic stenosis present with concomitant mitral regurgitation (MR). Cardiac
imaging plays a key role in identifying prognostic factors of MR persistence
after transcatheter aortic valve replacement (TAVR) and for planning its
treatment. METHODS: A total of 1,110 patients with severe aortic stenosis from 6
centers who underwent TAVR were included. In-hospital to 6-month follow-up
clinical outcomes according to the degree of baseline MR were evaluated. Off-line
analysis of echocardiographic and multidetector computed tomography images was
performed to determine predictors of improvement, clinical outcomes, and
potential percutaneous alternatives to treat persistent MR. RESULTS: Compared
with patients without significant pre-TAVR MR, 177 patients (16%) presented with
significant pre-TAVR MR, experiencing a 3-fold increase in 6-month mortality
(35.0% vs. 10.2%; p < 0.001). After TAVR, the degree of MR improved in 60% of
them. A mitral annular diameter of >35.5 mm (odds ratio: 9.0; 95% confidence
interval: 3.2 to 25.3; p < 0.001) and calcification of the mitral apparatus by
multidetector computed tomography (odds ratio: 11.2; 95% confidence interval:
4.03 to 31.3; p < 0.001) were independent predictors of persistent MR. At least
14 patients (1.3% of the entire cohort, 13.1% of patients with persistent MR) met
criteria for percutaneous mitral repair with either MitraClip (9.3%) or a balloon
expandable valve (3.8%). CONCLUSIONS: Significant MR is not uncommon in TAVR
recipients and associates with greater mortality. In more than one-half of
patients, the degree of MR improves after TAVR, which can be predicted by
characterizing the mitral apparatus with multidetector computed tomography.
According to standardized imaging criteria, at least 1 in 10 patients whose MR
persists after TAVR could benefit from percutaneous mitral procedures, and even
more could be treated with MitraClip after dedicated pre-imaging evaluation.
PMID- 27491613
TI - Valve Type, Size, and Deployment Location Affect Hemodynamics in an In Vitro
Valve-in-Valve Model.
AB - OBJECTIVES: The purpose of this study was to optimize hemodynamic performance of
valve-in-valve (VIV) according to transcatheter heart valve (THV) type (balloon
vs. self-expandable), size, and deployment positions in an in vitro model.
BACKGROUND: VIV transcatheter aortic valve replacement is increasingly used for
the treatment of patients with a failing surgical bioprosthesis. However, there
is a paucity in understanding the THV hemodynamic performance in this setting.
METHODS: VIV transcatheter aortic valve replacement was simulated in a
physiologic left heart simulator by deploying a 23-mm SAPIEN, 23-mm CoreValve,
and 26-mm CoreValve within a 23-mm Edwards PERIMOUNT surgical bioprosthesis. Each
THV was deployed into 5 different positions: normal (inflow of THV was juxtaposed
with inflow of surgical bioprosthesis), -3 and -6 mm subannular, and +3 and +6 mm
supra-annular. At a heart rate of 70 bpm and cardiac output of 5.0 l/min, mean
transvalvular pressure gradients (TVPG), regurgitant fraction (RF), effective
orifice area, pinwheeling index, and pullout forces were evaluated and compared
between THVs. RESULTS: Although all THV deployments resulted in hemodynamics that
would have been consistent with Valve Academic Research Consortium-2 procedure
success, we found significant differences between THV type, size, and deployment
position. For a SAPIEN valve, hemodynamic performance improved with a supra
annular deployment, with the best performance observed at +6 mm. Compared with a
normal position, +6 mm resulted in lower TVPG (9.31 +/- 0.22 mm Hg vs. 11.66 +/-
0.22 mm Hg; p < 0.01), RF (0.95 +/- 0.60% vs. 1.27 +/- 0.66%; p < 0.01), and PI
(1.23 +/- 0.22% vs. 3.46 +/- 0.18%; p < 0.01), and higher effective orifice area
(1.51 +/- 0.08 cm(2) vs. 1.35 +/- 0.02 cm(2); p < 0.01) at the cost of lower
pullout forces (5.54 +/- 0.20 N vs. 7.09 +/- 0.49 N; p < 0.01). For both
CoreValve sizes, optimal deployment was observed at the normal position. The 26
mm CoreValve, when compared with the 23-mm CoreValve and 23-mm SAPIEN, had a
lower TVPG (7.76 +/- 0.14 mm Hg vs. 10.27 +/- 0.18 mm Hg vs. 9.31 +/- 0.22 mm Hg;
p < 0.01) and higher effective orifice area (1.66 +/- 0.05 cm(2) vs. 1.44 +/-
0.05 cm(2) vs. 1.51 +/- 0.08 cm(2); p < 0.01), RF (4.79 +/- 0.67% vs. 1.98 +/-
0.36% vs. 0.95 +/- 1.68%; p < 0.01), PI (29.13 +/- 0.22% vs. 6.57 +/- 0.14% vs.
1.23 +/- 0.22%; p < 0.01), and pullout forces (10.65 +/- 0.66 N vs. 5.35 +/- 0.18
N vs. 5.54 +/- 0.20 N; p < 0.01). CONCLUSIONS: The optimal deployment location
for VIV in a 23 PERIMOUNT surgical bioprosthesis was at a +6 mm supra-annular
position for a 23-mm SAPIEN valve and at the normal position for both the 23-mm
and 26-mm CoreValves. The 26-mm CoreValve had lower gradients, but higher RF and
PI than the 23-mm CoreValve and the 23-mm SAPIEN. In their optimal positions, all
valves resulted in hemodynamics consistent with the definitions of Valve Academic
Research Consortium-2 procedural success. Long-term studies are needed to
understand the clinical impact of these hemodynamic performance differences in
patients who undergo VIV transcatheter aortic valve replacement.
PMID- 27491614
TI - Late Displacement After Transcatheter Mitral Valve Replacement for Degenerative
Mitral Valve Disease With Massive Annular Calcification.
PMID- 27491615
TI - More Stories.
PMID- 27491616
TI - Interventional Treatment of a Failing Pulmonic and Tricuspid Bioprosthesis in
Hedinger Syndrome.
PMID- 27491617
TI - Late Presentation of a Semicomplete Occluded Right Coronary Artery by a Direct
Flow Valve Preventing Interventional Therapy for ST-Segment Elevation Myocardial
Infarction.
PMID- 27491618
TI - Short-term interval training at both lower and higher intensities in the severe
exercise domain result in improvements in VO2 on-kinetics.
AB - PURPOSE: Although high-intensity interval training (HIT) seems to promote greater
improvements in aerobic parameters than continuous training, the influence of
exercise intensity on [Formula: see text] on-kinetics remains under
investigation. METHODS: After an incremental test, twenty-one recreationally
trained cyclists performed several time-to-exhaustion tests to determine critical
power (CP), and the highest intensity (I HIGH), and the lowest exercise duration
(T LOW) at which [Formula: see text] is attained during constant exercise.
Subjects also completed a series of step transitions to moderate- and heavy
intensity work rates to determine pulmonary [Formula: see text] on-kinetics.
Surface electromyography (EMG) of vastus lateralis muscle and blood lactate
accumulation (?BLC) was measured during heavy exercise. Subjects were assigned to
one of two 4-week work-matched training groups: the lower [105 % CP: n = 11; 4 *
5 min at 105 % CP (218 +/- 39 W), 1 min recovery] or the upper [I HIGH: n = 10; 8
* 100 % I HIGH (355 +/- 60 W), 1:2 work:recovery ratio] intensity of the severe
exercise domain. RESULTS: The two interventions were similarly effective in
reducing the phase II [Formula: see text] time constant during moderate (105 %
CP: 34 +/- 13 to 25 +/- 8 s; I HIGH: 31 +/- 9 to 23 +/- 6 s) and heavy exercise
(105 % CP: 25 +/- 7 to 18 +/- 5 s; I HIGH: 27 +/- 7 to 16 +/- 5 s) and in
reducing the amplitude of [Formula: see text] slow component, EMG amplitude, and
?BLC during heavy exercise. CONCLUSION: In conclusion, the short-term adjustments
in response to step transitions to moderate and heavy exercise were independent
of training intensity within the severe exercise domain.
PMID- 27491619
TI - The effect of high-intensity cycling training on postural sway during standing
under rested and fatigued conditions in healthy young adults.
AB - PURPOSE: The purpose of this study was to investigate whether high-intensity
cycling training leads to adapted responses of balance performance in response to
exercise-induced muscle fatigue. METHODS: Eighteen healthy adults were assigned
to either 3-weeks (n = 8, age 20.1 +/- 2.6 years, height 177 +/- 5 cm, mass 73.6
+/- 5.1 kg) or 6-weeks (n = 10, age 24.3 +/- 5.8 years, height 179 +/- 6 cm, mass
81.0 +/- 15.8 kg) of high-intensity training (HIT) on a cycle ergometer. The
centre of pressure (COP) displacement in the anteroposterior (COPAP) direction
and COP path length (COPL) were measured before and after the first and final
high-intensity training sessions. RESULTS: Pre-training, exercise-induced fatigue
elicited an increase in COPAP (3-weeks; p = 0.001, 6-weeks; p = 0.001) and COPL
(3-weeks; p = 0.002, 6-weeks; p = 0.001) returning to pre-exercise levels within
10-min of recovery. Following 3-weeks of training, significant increases in COPAP
(p = 0.001) and COPL (p = 0.002) were observed post-fatigue, returning to pre
exercise levels after 15-min of recovery. After 6-weeks of training no
significant increases in sway (COPAP; p = 0.212, COPL; p = 0.998) were observed
following exercise-induced fatigue. CONCLUSIONS: In summary, 3 weeks of HIT
resulted in longer recovery times following fatigue compared to pre-training
assessments. After 6 weeks of HIT, postural sway following fatigue was
attenuated. These results indicate that HIT could be included in injury
prevention programmes, however, caution should be taken during early stages of
the overreaching process.
PMID- 27491621
TI - Using the dendritic polymer PAMAM to form gold nanoparticles in the protein cage
thermosome.
AB - The chaperonin thermosome (THS) is a protein cage that lacks binding sites for
metal ions and inorganic nanoparticles. However, when poly(amidoamine) (PAMAM) is
encapsulated into THS, gold nanoparticles (AuNP) can be prepared in the THS. The
polymer binds HAuCl4. Subsequent reduction yields nanoparticles with narrow size
distribution in the protein-polymer conjugate.
PMID- 27491620
TI - The impact of sleeping with reduced glycogen stores on immunity and sleep in
triathletes.
AB - PURPOSE: We investigated the effects of a 3-week dietary periodization on
immunity and sleep in triathletes. METHODS: 21 triathletes were divided into two
groups with different nutritional guidelines during a 3-week endurance training
program including nine twice a day sessions with lowered (SL group) or maintained
(CON group) glycogen availability during the overnight recovery period. In
addition to performance tests, sleep was monitored every night. Systemic and
mucosal immune parameters as well as the incidence of URTI were monitored every
week of the training/nutrition protocol. Two-ways ANOVA and effect sizes were
used to examine differences in dependent variables between groups at each time
point. RESULTS: The SL group significantly improved 10 km running performance (-1
min 13 s, P < 0.01, d = 0.38), whereas no improvement was recorded in the CON
group (-2 s, NS). No significant changes in white blood cells counts, plasma
cortisol and IL-6 were recorded over the protocol in both groups. The vitamin D
status decreased in similar proportions between groups, whereas salivary IgA
decreased in the SL group only (P < 0.05, d = 0.23). The incidence of URTI was
not altered in both groups. All participants in both groups went to bed earlier
during the training program (SL -20 min, CON -27 min, P < 0.05, d = 0.28). In the
SL group, only sleep efficiency slightly decreased by 1.1 % (P < 0.05, d = 0.25)
and the fragmentation index tended to increase at the end of the protocol (P =
0.06). CONCLUSION: Sleeping and training the next morning regularly with reduced
glycogen availability has minimal effects on selected markers of immunity, the
incidence of URTI and sleeping patterns in trained athletes.
PMID- 27491622
TI - Core-Shell Silver/Polymeric Nanoparticles-Based Combinatorial Therapy against
Breast Cancer In-vitro.
AB - The current study aimed at preparing AgNPs and three different core-shell
silver/polymeric NPs composed of Ag core and three different polymeric shells:
polyvinyl alcohol (PVA), polyethylene glycol (PEG) and polyvinylpyrrolidone
(PVP). Thereafter, the core/shell NPs were loaded with a chemotherapeutic agent
doxorubicin (DOX). Finally, the cytotoxic effects of the different core-shell
Ag/polymeric NPs-based combinatorial therapeutics were tested in-vitro against
breast cancer (MCF-7) and human fibroblast (1BR hTERT) cell lines. AgNPs, Ag/PVA
and Ag/PVP NPs were more cytotoxic to MCF-7 cells than normal fibroblasts, as
well as DOX-Ag, DOX-Ag/PVA, DOX-Ag/PEG and DOX-Ag/PVP nanocarriers (NCs).
Notably, low dosage of core-shell DOX-loaded Ag/polymeric nanocarriers (NCs)
exhibited a synergic anticancer activity, with DOX-Ag/PVP being the most
cytotoxic. We believe that the prepared NPs-based combinatorial therapy showed a
significant enhanced cytotoxic effect against breast cancer cells. Future studies
on NPs-based combinatorial therapy may aid in formulating a novel and more
effective cancer therapeutics.
PMID- 27491625
TI - Cryogenic Trapping and Isotope Editing Identify a Protonated Water Cluster as an
Intermediate in the Photosynthetic Oxygen-Evolving Reaction.
AB - Internal water is known to play a catalytic role in several enzymes. In
photosystem II (PSII), water is the substrate. To oxidize water, the PSII Mn4CaO5
cluster or oxygen evolving center (OEC) cycles through five oxidation states,
termed Sn states. As reaction products, molecular oxygen is released, and protons
are transferred through a ~25 A hydrogen-bonded network from the OEC to the
thylakoid lumen. Previously, it was reported that a broad infrared band at 2880
cm(-1) is produced during the S1-to-S2 transition and accompanies flash-induced,
S state cycling at pH 7.5. Here, we report that when the S2 state is trapped by
continuous illumination under cryogenic conditions (190 K), an analogous
2740/2900 cm(-1) band is observed. The frequency depended on the sodium chloride
concentration. This band is unambiguously assigned to a normal mode of water by
D2(16)O and H2(18)O solvent exchange. Its large, apparent H2(18)O isotope shift,
ammonia sensitivity, frequency, and intensity support assignment to a stretching
vibration of a hydronium cation, H3O(+), in a small, protonated internal water
cluster, nH2O(H3O(+)). Water OH stretching bands, which may be derived from the
hydration shell of the hydronium ion, are also identified. Using the 2740 cm(-1)
infrared marker, the results of calcium depletion and strontium reconstitution on
the protonated water cluster are found to be pH dependent. This change is
attributed to protonation of an amino acid side chain and a possible change in
nH2O(H3O)(+) localization in the hydrogen-bonding network. These results are
consistent with an internal water cluster functioning as a proton acceptor and an
intermediate during the S1-to-S2 transition. Our experiments demonstrate the
utility of this infrared signal as a novel functional probe in PSII.
PMID- 27491624
TI - Insights into age-old questions of new dendritic spines: From form to function.
AB - Principal neurons in multiple brain regions receive a vast majority of excitatory
synaptic contacts on the tiny dendritic appendages called dendritic spines. These
structures are believed to be the locus of memory storage in the brain. Indeed,
neurological diseases leading to impairment in memory and cognitive capabilities
are often associated with structural alteration of dendritic spines. While
several landmark studies in the past have provided a great deal of information on
the structure, function and molecular composition of prototypical mature
dendritic spines, we still have a limited knowledge of nascent spines. In recent
years there has been a surge of interest to understand the nascent spines and the
increasing technical advances in the genetic, molecular and imaging methods have
opened avenues for systematic and thorough investigation. In this review, by
discussing studies from several labs including ours, we provide a systematic
summary of the development, structure, molecular expression and function of
nascent spines and highlight some of the potentially important and interesting
research questions that remain to be answered.
PMID- 27491626
TI - Merging thiophene with boron: new building blocks for conjugated materials.
AB - This perspective highlights recent progress on the design, synthesis and
applications of thienylboranes as building blocks for new functional materials.
Well-controlled synthetic protocols, such as boron-tin and boron-silicon exchange
reactions, hydroboration of alkynyl groups, and electrophilic borylations provide
opportunities to access thiophene-boranes that are chemically robust and display
desirable photophysical properties, redox characteristics, and solid-state
assembly behavior. Diverse protocols for further functionalization allow for
facile integration into larger conjugated structures and even polymeric systems.
Moreover, the strong Lewis acid character that is characteristic of trivalent
boranes facilitates intra- and intermolecular Lewis acid-base interactions that
can further enrich the chemical and electronic properties of thiophene-borane
materials. Recent advances with respect to applications in sensing, organic
electronics, and the development of molecular switches are also discussed.
PMID- 27491623
TI - Actin filament-microtubule interactions in axon initiation and branching.
AB - Neurons begin life as spherical cells. A major hallmark of neuronal development
is the formation of elongating processes from the cell body which subsequently
differentiate into dendrites and the axon. The formation and later development of
neuronal processes is achieved through the concerted organization of actin
filaments and microtubules. Here, we review the literature regarding recent
advances in the understanding of cytoskeletal interactions in neurons focusing on
the initiation of processes from neuronal cell bodies and the collateral
branching of axons. The complex crosstalk between cytoskeletal elements is
mediated by a cohort of proteins that either bind both cytoskeletal systems or
allow one to regulate the other. Recent studies have highlighted the importance
of microtubule plus-tip proteins in the regulation of the dynamics and
organization of actin filaments, while also providing a mechanism for the
subcellular capture and guidance of microtubule tips by actin filaments. Although
the understanding of cytoskeletal crosstalk and interactions in neuronal
morphogenesis has advanced significantly in recent years the appreciation of the
neuron as an integrated cytoskeletal system remains a frontier.
PMID- 27491627
TI - Laparoscopic mesh repair for lumbar hernia after iliac crest bone harvest.
AB - Lumbar hernia after iliac crest bone harvest is relatively rare. When it does
occur, it presents as a flank abdominal protrusion through a lateroposterior
abdominal wall defect. A laparoscopic approach for this type of hernia is
reported to have advantages over the classic open method. Here, we present a case
of a 49-year-old Caucasian man who presented with an enlarged left flank mass
after iliac bone harvest for pseudarthrosis. He had undergone open onlay mesh
repair for inferior lumbar hernia, but the hernia recurred 3 months
postoperatively. Laparoscopic intraperitoneal onlay mesh repair using a composite
mesh was performed 7 months after recurrence. The patient was discharged 6 days
postoperatively without complications. No signs of recurrence were detected
during 1-year follow-up period. The laparoscopic approach for lumbar hernia
conferred excellent visualization of the hernia defect and enabled a safe mesh
repair using intra-abdominal pressure to hold it in position. This approach
provided all the benefits of minimally invasive surgery.
PMID- 27491629
TI - Imaging the surface morphology, chemistry and conductivity of LiNi1/3Fe1/3Mn4/3O4
crystalline facets using scanning transmission X-ray microscopy.
AB - Scanning transmission X-ray microscopy (STXM) using the X-ray fluorescence mode
has been employed to elucidate the chemical structures at Ni, Fe, Mn and O sites
from the (111) and (100) facets of micron-sized LiNi1/3Fe1/3Mn4/3O4 energy
material particles. Furthermore, STXM imaging using electron yield mode has
mapped out the surface conductivity of the crystalline particles. This study
presents a novel approach that visualizes local element segregation, chemistry
and conductivity variation among different crystal facets, which will assist
further tailoring of the morphology and surface structure of this high voltage
spinel lithium ion battery cathode material.
PMID- 27491628
TI - Wastewater-Based Epidemiology To Monitor Synthetic Cathinones Use in Different
European Countries.
AB - Synthetic cathinones are among the most consumed new psychoactive substances
(NPS), but their increasing number and interchangeable market make it difficult
to estimate the real size of their consumption. Wastewater-based epidemiology
(WBE) through the analysis of metabolic residues of these substances in urban
wastewater can provide this information. This study applied WBE for the first
time to investigate the presence of 17 synthetic cathinones in four European
countries. A method based on solid-phase extraction and liquid chromatography
coupled to tandem mass spectrometry was developed, validated, and used to
quantify the target analytes. Seven substances were found, with mephedrone and
methcathinone being the most frequently detected and none of the analytes being
found in Norway. Population-normalized loads were used to evaluate the pattern of
use, which indicated a higher consumption in the U.K., followed by Spain and
Italy, in line with the European prevalence data from population surveys. In the
U.K., where an entire week was investigated, an increase of the loads was found
during the weekend, indicating a preferential use in recreational contexts. This
study demonstrated that WBE can be a useful additional tool to monitor the use of
NPS in a population.
PMID- 27491630
TI - Enantiodivergent Atroposelective Synthesis of Chiral Biaryls by Asymmetric
Transfer Hydrogenation: Chiral Phosphoric Acid Catalyzed Dynamic Kinetic
Resolution.
AB - Reported herein is an enantiodivergent synthesis of chiral biaryls by a chiral
phosphoric acid catalyzed asymmetric transfer hydrogenation reaction. Upon
treatment of biaryl lactols with aromatic amines and a Hantzsch ester in the
presence of chiral phosphoric acid, dynamic kinetic resolution (DKR) involving a
reductive amination reaction proceeded smoothly to furnish both R and S isomers
of chiral biaryls with excellent enantioselectivities by proper choice of
hydroxyaniline derivative. This trend was observed in wide variety of substrates,
and various chiral biphenyl and phenyl naphthyl adducts were synthesized with
satisfactory enantioselectivities in enantiodivergent fashion. The
enantiodivergent synthesis of synthetically challenging, chiral o
tetrasubstituted biaryls were also accomplished, and suggests high synthetic
potential of the present method.
PMID- 27491632
TI - Erratum.
PMID- 27491631
TI - Controversies in Surgical Management of Recalcitrant Enthesopathy of the Extensor
Carpi Radialis Brevis.
AB - Enthesopathy of the extensor carpi radialis brevis, often referred to as "tennis
elbow," is common and responds to nonsurgical treatment in 80% to 90% of patients
within 1 year. For those who proceed with surgery, much remains unclear regarding
the ideal treatment. This paper discusses controversies in surgical management of
extensor carpi radialis brevis enthesopathy including clinical outcomes of open
versus arthroscopic techniques, the relevance of concomitant pathology addressed
arthroscopically, and avenues for assessing comparative cost data.
PMID- 27491633
TI - Compliance with cochlear implantation in children subsequently diagnosed with
autism spectrum disorder.
AB - OBJECTIVE: To assess the compliance with cochlear implantation (CI) in children
subsequently diagnosed with autism spectrum disorder (ASD). METHODS: This was a
retrospective case review and survey performed at a tertiary referral centre.
Children meeting the criteria for CI who were implanted between 1989 and 2015 and
who subsequently received a diagnosis of ASD were included. The primary outcome
measure was to assess compliance with CI in children subsequently diagnosed with
ASD. Secondary outcome measures included assessment of pre-CI risk factors that
may have identified children at higher risk of a subsequent diagnosis of ASD, as
well as the benefit obtained by these children following CI. RESULTS: 1050
children were implanted between 1989 and 2015. Of these, 22 children were
diagnosed with ASD after receiving their CI. The average age at implantation was
2.6 years (median 3, range 1-8 years). The average age for diagnosis of ASD was 5
years, approximately 2 years (median 22 months, range 2-85 months) following CI.
Of these, 16/22 (712.7%) regularly use their CI. 6/22 (27.2%) children became non
users of their implant. Some degree of verbal communication was used by 13/22
(59%) of our studied group. CONCLUSION: There is a range of level of disabilities
in ASD, with some relatively minor social communication difficulties through to
severe language, cognitive, and behavioural difficulties. Compliance with CI is
variable and appears to correlate with the severity of the ASD. Preoperative
counselling should include information about the possible impact of later
diagnosed disabilities such as ASD on performance.
PMID- 27491634
TI - Effects of histidin-2-ylidene vs. imidazol-2-ylidene ligands on the anticancer
and antivascular activity of complexes of ruthenium, iridium, platinum, and gold.
AB - Couples of N-heterocyclic carbene complexes of ruthenium, iridium, platinum, and
gold, each differing only in the carbene ligand being either 1,3-dimethylimidazol
2-ylidene (IM) or 1,3-dimethyl-N-boc-O-methylhistidin-2-ylidene (HIS), were
assessed for their antiproliferative effect on seven cancer cell lines, their
interaction with DNA, their cell cycle interference, and their vascular
disrupting properties. In MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide] assays only the platinum complexes were cytotoxic at
single-digit micromolar IC50 concentrations with the (HIS)Pt complex being on
average twice as active as the (IM)Pt complex. The former was highly efficacious
against cisplatin-resistant HT-29 colon carcinoma cells where the latter had no
effect. Both Pt complexes were accumulated by cancer cells and bound to double
helical DNA equally well. Only the (HIS)Pt complex modified the electrophoretic
mobility of circular DNA in vitro due to the HIS ligand causing greater
morphological changes to the DNA. Both platinum complexes induced accumulation of
518A2 melanoma cells in G2/M and S phase of the cell cycle. A disruption of blood
vessels in the chorioallantoic membrane of fertilized chicken eggs was observed
for both platinum complexes and the (IM)gold complex. The (HIS)platinum complex
was as active as cisplatin in tumor xenografted mice while being tolerated
better. We found that the HIS ligand may augment the cytotoxicity of certain
antitumoral metal fragments in two ways: by acting as a transmembrane carrier
increasing the cellular accumulation of the complex, and by initiating a
pronounced distortion and unwinding of DNA. We identified a new (HIS)platinum
complex which was highly cytotoxic against cancer cells including cisplatin
resistant ones.
PMID- 27491635
TI - Associated ultrasonographic findings in fetuses with microcephaly because of
suspected Zika virus (ZIKV) infection during pregnancy.
AB - OBJECTIVE: To describe fetal ultrasonographic findings and outcomes in a series
of cases of fetal microcephaly associated with Zika virus infection. METHODS:
Retrospective case series of microcephaly with definite (laboratory evidence) or
highly probable (specific neuroimaging findings and negative laboratory results)
maternal Zika virus infection. Microcephaly was graded as mild if the head
circumference was between 2 and 3 standard deviation (SD) below the mean, and
severe if 3 or more SD below the mean. Associated central nervous system (CNS)
and extracranial malformations are described. RESULTS: Nineteen singleton
pregnancies fulfilling the inclusion criteria were identified. Severe
microcephaly and mild microcephaly were identified in 14 and 5 fetuses,
respectively. Additional CNS malformations were present in 17 cases and 7 had
extracranial congenital anomalies. Symptoms were reported in 13/19 cases at a
gestational age between 5 and 16 weeks. Mean (+/-SD) gestational age at
ultrasound diagnosis was 32.3 +/- 5.1 weeks. Amniocentesis was performed in five
cases at a median gestational age of 31 weeks (range 28-38) and was positive for
Zika virus RT-PCR in two cases. There were three neonatal deaths and one
stillbirth. CONCLUSION: In the presence of fetal microcephaly associated with
Zika virus infection, CNS malformations are frequently detected. (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27491637
TI - Nuclear respiratory factor-1 (NRF-1) regulated hypoxia-inducible factor-1alpha
(HIF-1alpha) under hypoxia in HEK293T.
AB - Hypoxia-inducible factor 1alpha (HIF-1alpha) is a master regulator of oxygen
homeostasis. Under hypoxia, the active HIF1-alpha subunits are mainly regulated
through increased protein stabilization. Little is known concerning HIF-1alpha
transcriptional regulation. Nuclear respiratory factor 1 (NRF-1) is a DNA-binding
transcription factor that regulates mitochondrial biogenesis. In this study, we
showed that NRF-1was a repressor of HIF-1alpha. The cellular depletion of NRF-1
by siRNA targeting leads to increased HIF-1alphatranscriptional activity. EMSA,
ChIP and luciferase activity allowed the identification of two functional NRF-1
binding sites within HIF-1alpha promoter. This study therefore identifies NRF-1
as a novel regulator of HIF-1alpha. (c) 2016 IUBMB Life, 68(9):748-755, 2016.
PMID- 27491636
TI - Curcumin improves episodic memory in cadmium induced memory impairment through
inhibition of acetylcholinesterase and adenosine deaminase activities in a rat
model.
AB - Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes
has been reported to exert cognitive enhancing potential with limited scientific
basis. Hence, this study sought to evaluate the effect of curcumin on cerebral
cortex acetylcholinesterase (AChE) and adenosine deaminase (ADA) activities in
cadmium (Cd)-induced memory impairment in rats. Animals were divided into six
groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25
mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. Rats
received Cd (2.5 mg/kg) and curcumin (12.5 and 25 mg/kg, respectively) by gavage
for 7 days. The results of this study revealed that cerebral cortex AChE and ADA
activities were increased in Cd-poisoned rats, and curcumin co-treatment reversed
these activities to the control levels. Furthermore, Cd intoxication increased
the level of lipid peroxidation in cerebral cortex with a concomitant decreased
in functional sulfuhydryl (-SH) group and nitric oxide (NO), a potent
neurotransmitter and neuromodulatory agent. However, the co-treatment with
curcumin at 12.5 and 25 mg/kg, respectively increased the non-enzymatic
antioxidant status and NO in cerebral cortex with a decreased in malondialdehyde
(MDA) level. Therefore, inhibition of AChE and ADA activities as well as
increased antioxidant status by curcumin in Cd-induced memory dysfunction could
suggest some possible mechanism of action for their cognitive enhancing
properties.
PMID- 27491638
TI - Effective carbon and nitrogen removal with reduced sulfur oxidation in an
anaerobic baffled reactor for fresh leachate treatment.
AB - The application of an anaerobic baffled reactor (ABR) with four compartments was
investigated for the simultaneous removal of carbon and nitrogen from leachate.
The nitrified effluent was recycled to compartment 3 of the ABR, thereby avoiding
the adverse influence of nitrogen oxides on anaerobic methanogenesis in
compartment 1. Nitrified effluent recirculation not only enhanced chemical oxygen
demand removal (>95.6%) but also improved the total nitrogen removal efficiency
from 12.7% to 67.4% with increasing recirculation ratio from 0.25 to 2. The
challenge of insufficient carbon sources for heterotrophic denitrification in
compartment 3 with a high recirculation ratio could be overcome by step feeding
of leachate. Moreover, various reduced sulfurs (e.g., sulfide, elemental sulfur,
and organic sulfur) were involved in nitrate reduction via sulfur-based
autotrophic denitrification. The addition of sulfide to compartment 3 further
confirmed nitrate reduction using reduced sulfur as an electron donor. The
interaction of organic carbon, reduced sulfur, and nitrate in leachate treatment
needs further study.
PMID- 27491639
TI - Is there a correlation between time of delivery and newborn cord pH?
AB - PURPOSE: Since more senior and attending physicians work in labor wards during
morning shifts, we expect a better delivery outcome during that time period.
MATERIALS AND METHODS: A retrospective study was conducted between 1/2005 and
12/2014. Records of 56 428 singleton deliveries from a tertiary hospital in which
cord blood pH was routinely measured at birth were analyzed. Time of birth was
divided into shifts: 7 AM-3 PM (morning shift), 3 PM-11 PM (afternoon shift), and
11 PM-7 AM (night shift). Additional stratification compared weekdays and weekend
deliveries. RESULTS: 19 601, 18 429, and 18 398 neonates were born during
morning, afternoon, and night shifts, respectively. There was no significant
difference in maternal age, neonatal weight, or mean 5-min Apgar score among the
three shift periods. Furthermore, there was no correlation between shift time of
delivery and newborn acidosis with respect to cord pH less than 7 (0.1% in each
time periods, p = 0.67). Despite the above, instrumental deliveries and cesarean
sections were more common in the morning shift compared to the afternoon and
night shift, respectively (p = 0.001 each). CONCLUSIONS: Although shift time of
delivery was found to be related to mode of delivery it was not related to either
5-min Apgar score or newborn acidosis as reflected by cord pH.
PMID- 27491641
TI - Impact of prior treatment on patients with relapsed multiple myeloma treated with
carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3
ENDEAVOR study.
AB - The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and
dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple
myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients
categorized by number of prior lines of therapy or by prior treatment. Median
progression-free survival (PFS) for patients with one prior line was 22.2 months
for Kd vs 10.1 months for Vd, and median PFS for patients with ?2 prior lines was
14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib
exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for
patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd
vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one
prior line), 72.0 vs 59.7% (?2 prior lines), 71.2 vs 60.3% (prior bortezomib) and
70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines
subgroups was qualitatively similar to that in the broader ENDEAVOR population.
In RMM, outcomes are improved when receiving treatment with carfilzomib compared
with bortezomib, regardless of the number of prior therapy lines or prior
exposure to bortezomib or lenalidomide.
PMID- 27491642
TI - Hypertension might be a risk factor for erectile dysfunction: a meta-analysis.
AB - The study aimed to evaluate whether hypertension was a risk factor for erectile
dysfunction (ED). Databases including PubMed and Embase were retrieved to
identify studies related to hypertension in ED patients. Odds ratio (OR) and 95%
confidence interval (CI) were used as the effect size. Subgroup analyses
stratified by total number of enrolled subjects and research regions were
performed. Sensitivity analysis was performed by removing a single study at one
time. Egger's test was used to evaluate the publication bias. Totally, 40 studies
including 121,641 subjects were included in the meta-analysis. As a result,
hypertension was closely related to ED (OR = 1.74, 95% CI, 0.63-0.80, p < .01).
Subgroup analysis indicated hypertension was the risk factor for ED whatever the
participants numbers. When stratified by different regions, hypertension was a
risk factor for ED in Africa (OR = 3.35, 95% CI, 1.45-7.77, p < .01), Americas
(OR = 1.97, 95% CI, 1.68-2.31, p < 0.01), Asia (OR = 1.46, 95% CI, 1.16-1.84, p <
.01) and Europe (OR = 1.83, 95% CI, 1.34-2.49, p < .01), but not in Australia.
Hypertension may be a potential risk factor for ED.
PMID- 27491640
TI - Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition
from minicircle vectors.
AB - Immunotherapy with T cell modified with gamma-retroviral or lentiviral (LV)
vectors to express a chimeric antigen receptor (CAR) has shown remarkable
efficacy in clinical trials. However, the potential for insertional mutagenesis
and genotoxicity of viral vectors is a safety concern, and their cost and
regulatory demands a roadblock for rapid and broad clinical translation. Here, we
demonstrate that CAR T cells can be engineered through non-viral Sleeping Beauty
(SB) transposition of CAR genes from minimalistic DNA vectors called minicircles
(MCs). We analyzed genomic distribution of SB and LV integrations and show that a
significantly higher proportion of MC-derived CAR transposons compared with LV
integrants had occurred outside of highly expressed and cancer-related genes into
genomic safe harbor loci that are not expected to cause mutagenesis or
genotoxicity. CD19-CAR T cells engineered with our enhanced SB approach conferred
potent reactivity in vitro and eradicated lymphoma in a xenograft model in vivo.
Intriguingly, electroporation of SB MCs is substantially more effective and less
toxic compared with conventional plasmids, and enables cost-effective rapid
preparation of therapeutic CAR T-cell doses. This approach sets a new standard in
advanced cellular and gene therapy and will accelerate and increase the
availability of CAR T-cell therapy to treat hematologic malignancies.
PMID- 27491643
TI - Contribution of Quantitative EEG to the Diagnosis of Early Cognitive Impairment
in Patients With Idiopathic Parkinson's Disease.
AB - Cognitive dysfunction can emerge during the clinical course of Parkinson's
disease (PD) even beginning in early stages, which requires extended
neuropsychological tests for diagnosis. There is need for rapid, feasible, and
practical tests in clinical practice to diagnose and monitor the patients without
causing any discomfort. We investigated the utility of quantitative analysis of
digital EEG (qEEG) for diagnosing subtle cognitive impairment in PD patients
without evident cognitive deficits (ie, "normal cognition"). We enrolled 45
patients with PD and age- matched 39 healthy controls in the study. All
participants had Mini-Mental State Examination (MMSE) score greater than 25. qEEG
analysis and extensive neuropsychological assessment battery were applied to all
participants. Test scores for frontal executive functions, verbal memory
processes, attention span, and visuospatial functions were significantly lower
than healthy controls ( P < .01). qEEG analysis revealed a significant increase
in delta, theta, and beta frequencies, and decrease in alpha frequency band in
cerebral bioelectrical activity in patient group. In addition, power spectral
ratios ([alpha + beta] / [delta + theta]) in frontal, central, temporal,
parietal, and occipital regions were significantly decreased in patients compared
with the controls. The slowing in EEG was moderately correlated with MMSE scores
( r = 0.411-0.593; P < .01). However, qEEG analysis and extensive
neuropsychological assessment battery were only in weak correlation ( r = 0.230
0.486; P < .05). In conclusion, qEEG analysis could increase the diagnostic power
in detecting subtle cognitive impairment in PD patients without evident cognitive
deficit, perhaps years before the clinical onset of dementia.
PMID- 27491644
TI - Live birth rate and number of blastomeres on day 2 transfer.
AB - PURPOSE: To investigate whether the presence of large fragment (LF) and abnormal
cell divisions (ACDs) has influenced the correlation between live birth rate and
number of blastomeres detected on day 2 by conventional scoring. METHODS: This
study included 578 embryos cultured in time lapse and selected for transfer by
conventional scoring on day 2. By time-lapse recordings, embryos were reassessed
to identify ACDs and/or LFs mistaken as blastomeres. The latter identifications
were used to recalculate fragmentation rate and the number of blastomeres. Life
birth rate according to number of blastomeres was compared in (a) embryos
selected by conventional scoring and (b) embryos reassessed by time lapse.
RESULTS: After conventional scoring, embryos with four cells had a significantly
higher pregnancy rate than embryos with less than four cells and embryos with
more than four cells. By time-lapse assessment, ACDs and/or recalculated
fragmentation >25 % was recognized in 106/578 (18.3 %) of transferred embryos.
None of them resulted in a live birth. After exclusion of these embryos, the
number of blastomeres on the day of transfer did not have any impact on life
birth rate. CONCLUSION: Conventional scoring on day 2 did not detect ACDs and LFs
mistaken as blastomeres. LFs can lead to a recalculated fragmentation rate to >25
%. No significant correlation between live birth rate and number of blastomeres
in day 2 embryos was observed when embryos with ACDs and fragmentation >25 % were
excluded. Recognition of ACDs and fragmentation >25 % is more predictive of live
birth than number of blastomeres.
PMID- 27491645
TI - Barriers and Facilitators to Community CPR Education in San Jose, Costa Rica.
AB - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) improves survival after
prehospital cardiac arrest. While community CPR training programs have been
implemented across the US, little is known about their acceptability in non-US
Latino populations. OBJECTIVES: The purpose of this study was to identify
barriers to enrolling in CPR training classes and performing CPR in San Jose,
Costa Rica. METHODS: After consulting 10 San Jose residents, a survey was
created, pilot-tested, and distributed to a convenience sample of community
members in public gathering places in San Jose. Questions included demographics,
CPR knowledge and beliefs, prior CPR training, having a family member with heart
disease, and prior witnessing of a cardiac arrest. Questions also addressed
barriers to enrolling in CPR classes (cost/competing priorities). The analysis
focused on two main outcomes: likelihood of registering for a CPR class and
willingness to perform CPR on an adult stranger. Odds ratios and 95% CIs were
calculated to test for associations between patient characteristics and these
outcomes. RESULTS: Among 371 participants, most were male (60%) and <40 years old
(77%); 31% had a college degree. Many had family members with heart disease
(36%), had witnessed a cardiac arrest (18%), were trained in CPR (36%), and knew
the correct CPR steps (70%). Overall, 55% (95% CI, 50-60%) indicated they would
"likely" enroll in a CPR class; 74% (95% CI, 70-78%) would perform CPR on an
adult stranger. Cardiopulmonary resuscitation class enrollment was associated
with prior CPR training (OR: 2.6; 95% CI, 1.6-4.3) and a prior witnessed cardiac
arrest (OR: 2.0; 95% CI, 1.1-3.5). Willingness to perform CPR on a stranger was
associated with a prior witnessed cardiac arrest (OR: 2.5; 95% CI, 1.2-5.4) and
higher education (OR: 1.9; 95% CI, 1.1-3.2). Believing that CPR does not work was
associated with a higher likelihood of not attending a CPR class (OR: 2.4; 95%
CI, 1.7-7.9). Fear of performing mouth-mouth, believing CPR is against God's
will, and fear of legal risk were associated with a likelihood of not attending a
CPR class and not performing CPR on a stranger (range of ORs: 2.4-3.9).
CONCLUSION: Most San Jose residents are willing to take CPR classes and perform
CPR on a stranger. To implement a community CPR program, barriers must be
considered, including misgivings about CPR efficacy and legal risk. Hands-only
CPR programs may alleviate hesitancy to perform mouth-to-mouth. Schmid KM , Mould
Millman NK , Hammes A , Kroehl M , Quiros Garcia R , Umana McDermott M ,
Lowenstein SR . Barriers and facilitators to community CPR education in San Jose,
Costa Rica. Prehosp Disaster Med. 2016;31(5):509-515.
PMID- 27491647
TI - Molecular Informatics: From Models to Systems and Beyond.
PMID- 27491646
TI - Gartanin induces cell cycle arrest and autophagy and suppresses migration
involving PI3K/Akt/mTOR and MAPK signalling pathway in human glioma cells.
AB - In central nervous system, glioma is the most common primary brain tumour. The
diffuse migration and rapid proliferation are main obstacles for successful
treatment. Gartanin, a natural xanthone of mangosteen, suppressed proliferation,
migration and colony formation in a time- and concentration-dependent manner in
T98G glioma cells but not in mouse normal neuronal HT22 cells. Gartanin, at low
micromole, led to cell cycle arrest in G1 phase accompanied by inhibited
expression level of G1 cell cycle regulatory proteins cyclin D1, while increased
expression level of cyclin-dependent kinase inhibitor p27Kip1. In addition, the
secretion and activity of matrix metalloproteinases 2/9 (MMP-2/-9) were
significantly suppressed in T98G cells treated with gartanin, and it might result
from modulating mitogen-activated protein kinases (MAPK) signalling pathway in
T98G glioma cells. Moreover, gartanin significantly induced autophagy in T98G
cells and increased GFP-LC3 punctate fluorescence accompanied by the increased
expression level of Beclin 1 and LC3-II, while suppressed expression level of
p62. Gartanin treatment resulted in obvious inhibition of PI3K/Akt/mTOR
signalling pathway, which is important in modulating autophagy. Notably, gartanin
mediated anti-viability was significantly abrogated by autophagy inhibitors
including 3-methyladenine (3-MA) and chloroquine (CQ). These results indicate
that anti-proliferation effect of gartanin in T98G cells is most likely via cell
cycle arrest modulated by autophagy, which is regulated by PI3K/Akt/mTOR
signalling pathway, while anti-migration effect is most likely via suppression of
MMP-2/-9 activity which is involved in MAPK signalling pathway.
PMID- 27491648
TI - Deep Learning in Drug Discovery.
AB - Artificial neural networks had their first heyday in molecular informatics and
drug discovery approximately two decades ago. Currently, we are witnessing
renewed interest in adapting advanced neural network architectures for
pharmaceutical research by borrowing from the field of "deep learning". Compared
with some of the other life sciences, their application in drug discovery is
still limited. Here, we provide an overview of this emerging field of molecular
informatics, present the basic concepts of prominent deep learning methods and
offer motivation to explore these techniques for their usefulness in computer
assisted drug discovery and design. We specifically emphasize deep neural
networks, restricted Boltzmann machine networks and convolutional networks.
PMID- 27491649
TI - Rational Design of Coumarin Derivatives as CK2 Inhibitors by Improving the
Interaction with the Hinge Region.
AB - Design of novel coumarin derivatives as CK2 inhibitors were attempted by
targeting the interaction with the hinge region. A set of substituents capable of
forming a hydrogen bond or halogen bond with the hinge region were screened in
silico, and trifluoromethyl emerges as a promising motif by forming favorable
electrostatic interaction and a presumable halogen bond with the hinge region. As
proof of concept, three trifluoromethyl derivatives of coumarin were synthesized
and tested in vitro. The results indicated that replacement of methyl by
trifluoromethyl leads to a modest 5-fold improvement in potency, with the most
active compound being 0.4 uM. The newly designed compounds were further screened
on one lung cancer cell line A549, showing low micromolar anti-proliferative
activity.
PMID- 27491650
TI - In Silico Investigation of the Neurotensin Receptor 1 Binding Site: Overlapping
Binding Modes for Small Molecule Antagonists and the Endogenous Peptide Agonist.
AB - The neurotensin receptor 1 (NTSR1) belongs to the family of 7TM, G protein
coupled receptors, and is activated by the 13-amino-acid peptide neurotensin
(NTS) that has been shown to play important roles in neurological disorders and
the promotion of cancer cells. Recently, a high-resolution x-ray crystal
structure of NTSR1 in complex with NTS8-13 has been determined, providing novel
insights into peptide ligand recognition by 7TM receptors. SR48692, a potent and
selective small molecule antagonist has previously been used extensively as a
tool compound to study NTSR1 receptor signaling properties. To investigate the
binding mode of SR48692 and other small molecule compounds to NTSR1, we applied
an Automated Ligand-guided Backbone Ensemble Receptor Optimization protocol
(ALiBERO), taking receptor flexibility and ligand knowledge into account.
Structurally overlapping binding poses for SR48692 and NTS8-13 were observed,
despite their distinct chemical nature and inverse pharmacological profiles. The
optimized models showed significantly improved ligand recognition in a large
scale virtual screening assessment compared to the crystal structure. Our models
provide new insights into small molecule ligand binding to NTSR1 and could
facilitate the structure-based design of non-peptide ligands for the evaluation
of the pharmacological potential of NTSR1 in neurological disorders and cancer.
PMID- 27491651
TI - Combination of In Silico Analysis and In Vitro Assay to Investigate Drug Response
to Human Epidermal Growth Factor Receptor 2 Mutations in Lung Cancer.
AB - The epidermal growth factor receptor 2 (HER2) has been established as an
important target of HER2-positive lung cancer, but somatic mutations in HER2
kinase domain are frequently observed that may cause drug resistance and
sensitivity for tyrosine kinase inhibitors (TKIs). In this study, the response
profile of 14 small-molecule TKIs upon 11 clinical HER2 mutations was
investigated systematically using a synthetic strategy that integrated in silico
analysis and in vitro assay to explore the structural basis, energetic property
and biological implication underlying the intermolecular interactions of TKIs
with wild-type and variant HER2. It is found that most clinical mutations are far
away from HER2 active site and thus can only address modest or moderate effect on
inhibitor binding. However, few single-point substations such as D769H and D769Y
as well as the gatekeeper mutation T798 M were predicted to cause strong
resistance for an array of TKIs by reshaping the geometric feature and
physiochemical property of the active site. Furthermore, inhibitor response to
the most common insertion mutation in HER2 exion 20 (HER2(YVMA) ) was examined in
detail; the response can be grouped into three classes: sensitization, resistance
and insusceptibility. The Bcr-Abl inhibitor bosutinib and EGFR inhibitor
gefitinib were selected as the representatives of, respectively, sensitization
and insusceptibility to perform kinase assay against the GST-tagged, recombinant
kinase domains of wild-type HER2(WT) and HER2(YVMA) variant. As expected, the
biological activity of bosutinib was improved by ~160-fold due to the insertion,
while gefitinib exhibited low inhibitory potency on both HER2(WT) and HER2(YVMA)
(IC50 >100 MUM). Structural analysis revealed an intensive network of hydrogen
bonds and hydrophobic interactions in HER2(YVMA) ?bosutinib complex, whereas only
few nonspecific van der Waals contacts were observed at the complex interface of
HER2(YVMA) with gefitinib.
PMID- 27491652
TI - Comparative Analysis of QSAR-based vs. Chemical Similarity Based Predictors of
GPCRs Binding Affinity.
AB - Ligand based virtual screening (LBVS) approaches could be broadly divided into
those relying on chemical similarity searches and those employing Quantitative
Structure-Activity Relationship (QSAR) models. We have compared the predictive
power of these approaches using some datasets of compounds tested against several
G-Protein Coupled Receptors (GPCRs). The k-Nearest Neighbors (kNN) QSAR models
were built for known ligands of each GPCR target independently, with a fraction
of tested ligands for each target set aside as a validation set. The prediction
accuracies of QSAR models for making active/inactive calls for compounds in both
training and validation sets were compared to those achieved by the Prediction of
Activity Spectra for Substances' (PASS) and the Similarity Ensemble Approach
(SEA) tools both available online. Models developed with the kNN QSAR method
showed the highest predictive power for almost all tested GPCR datasets. The PASS
software, which incorporates multiple end-point specific QSAR models demonstrated
a moderate predictive power, while SEA, a chemical similarity based approach, had
the lowest prediction power. Our studies suggest that when sufficient amount of
data is available to develop and rigorously validate QSAR models such models
should be chosen as the preferred virtual screening tool in ligand-based
computational drug discovery as compared to chemical similarity based approaches.
PMID- 27491653
TI - ADOMA: A Command Line Tool to Modify ClustalW Multiple Alignment Output.
AB - We present ADOMA, a command line tool that produces alternative outputs from
ClustalW multiple alignments of nucleotide or protein sequences. ADOMA can
simplify the output of alignments by showing only the different residues between
sequences, which is often desirable when only small differences such as single
nucleotide polymorphisms are present (e.g., between different alleles). Another
feature of ADOMA is that it can enhance the ClustalW output by coloring the
residues in the alignment. This tool is easily integrated into automated Linux
pipelines for next-generation sequencing data analysis, and may be useful for
researchers in a broad range of scientific disciplines including evolutionary
biology and biomedical sciences. The source code is freely available at
https://sourceforge. net/projects/adoma/.
PMID- 27491654
TI - Treatment outcome of PD-1 immune checkpoint inhibitor in Asian metastatic
melanoma patients: correlative analysis with PD-L1 immunohistochemistry.
AB - Overexpression of PD-L1 has been shown to be associated with better clinical
responses to PD-1/PD-L1 blockade in melanoma. However, the utility of PD-L1
immunostaining as a predictive biomarker for anti-PD-1 treatment remains unclear,
especially in melanoma of acral/mucosal origin. Materials and methods We
collected and reviewed the medical records of 37 patients with metastatic
melanoma who were treated with the anti-PD-1 antibodies pembrolizumab or
nivolumab between January and December 2015. Patients with histologically
diagnosed malignant melanoma and whose pretreatment tumor specimens were
available for immunohistochemical staining of PD-L1 expression in tumor or immune
cells were included. Results Of 37 patients, 26 patients had either acral or
mucosal melanoma. The overall response rate was 10.8 % (95 % CI, 0.8-20.8 %). The
response rate to PD-1 inhibitor was 11.5 % (95 % CI, 0-23.8 %) in acral/mucosal
melanoma and that for cutaneous melanoma was 9.1 % (95 % CI, 0-26.1 %). Of these
37 patients, 18 had pre-treatment tumor specimens available for PD-L1 staining.
Of 18 patients, 10 (55.5 %) were of acral/mucosal origin. In all patients with
acral melanoma, the overall response rate (ORR) was 16.7 % (1 of 6 patients) and
disease control rate (DCR) was 50 % (3 of 6 patients). In the PDL-1(+) melanoma
group (1 % cut-off value), ORR was 20 % (2/10) and DCR was 80 %; for PDL-1 (-)
group, ORR was 12.5 % (1/8) and DCR of 37.5 %. In the PDL-1 (+) group by 5 % cut
off value, ORR was 33.3 % (2/6) and DCR was 83.3 %; for patients with PDL-1 (-),
ORR was 8.3 % (1/12) and DCR was 50 %. The median PFS was 6.8 months in PDL-1(+)
group and 1.9 months in PDL-1(-) group (p = 0.149). Anti-PD-1 treatment was very
well tolerated without serious adverse events of grade 3 or 4 in all patients.
Conclusions The treatment outcome to PD-1 antibody was not different in
acral/mucosal melanoma when compared with cutaneous melanoma. The
immunohistochemical PD-L1 expression seemed to be correlated with better clinical
outcomes of anti-PD-1 treatment in limited cases.
PMID- 27491655
TI - Simultaneous occurrence of metabolic, hematologic, neurologic and cardiac
complications after Roux-en-Y gastric bypass for morbid obesity.
AB - Roux-en-Y gastric bypass (RYGB) is a commonly performed procedure in the surgical
treatment of morbid obesity. Since a major anatomical alteration is made, this
procedure may lead to significant postoperative complications, including
nutritional deficiencies related to malabsorption. As a consequence of
micronutrient deficiencies, secondary metabolic, hematologic and neurologic
complications might also develop. Each of these complications is well reported in
the literature; however, there are limited data on the simultaneous occurrence of
these complications in a single patient. In this report, we aimed to present the
diagnosis and management of metabolic, hematologic, neurologic and cardiac
complications, which occurred simultaneously in a 57-year-old female patient
after undergoing laparoscopic RYGB procedure.
PMID- 27491657
TI - Sharing experiences of clinical teaching: an evaluation of contrasting workshops.
PMID- 27491656
TI - Understanding and responding when things go wrong: key principles for primary
care educators.
AB - Learning from events with unwanted outcomes is an important part of workplace
based education and providing evidence for medical appraisal and revalidation. It
has been suggested that adopting a 'systems approach' could enhance learning and
effective change. We believe the following key principles should be understood by
all healthcare staff, especially those with a role in developing and delivering
educational content for safety and improvement in primary care. When things go
wrong, professional accountability involves accepting there has been a problem,
apologising if necessary and committing to learn and change. This is easier in a
'Just Culture' where wilful disregard of safe practice is not tolerated but where
decisions commensurate with training and experience do not result in blame and
punishment. People usually attempt to achieve successful outcomes, but when
things go wrong the contribution of hindsight and attribution bias as well as a
lack of understanding of conditions and available information (local rationality)
can lead to inappropriately blame 'human error'. System complexity makes
reduction into component parts difficult; thus attempting to 'find-and-fix'
malfunctioning components may not always be a valid approach. Finally,
performance variability by staff is often needed to meet demands or cope with
resource constraints. We believe understanding these core principles is a
necessary precursor to adopting a 'systems approach' that can increase learning
and reduce the damaging effects on morale when 'human error' is blamed. This may
result in 'human error' becoming the starting point of an investigation and not
the endpoint.
PMID- 27491658
TI - Can predilatation in transcatheter aortic valve implantation be omitted? - a
prospective randomized study.
AB - BACKGROUND: The use of a balloon expandable stent valve includes balloon
predilatation of the aortic stenosis before valve deployment. The aim of the
study was to see whether or not balloon predilatation is necessary in
transcatheter aortic valve replacement (TAVI). METHODS: Sixty consecutive TAVI
patients were randomized to the standard procedure or to a protocol where balloon
predilatation was omitted. RESULTS: There were no significant differences between
the groups regarding early hemodynamic results or complication rates.
CONCLUSIONS: TAVI can be performed safely without balloon predilatation and with
the same early results as achieved with the standard procedure including balloon
predilatation. The reduction in the number of pacing periods required may be
beneficial for the patient.
PMID- 27491659
TI - [Alcohol and the heart : Anecdotes on the history of a checkered relationship].
AB - The cultural and natural scientific ambivalence of the heart and alcohol has long
been the subject of philosophical, artistic, intellectual and emotional
discussions, not uncommonly in a romanticizing manner. The indulgence of
alcoholic beverages in moderation is contrasted by the inestimable risks and
dangers of alcohol abuse with many cardiovascular implications, such as cardiac
arrhythmia, cardiomyopathy and arterial hypertension. The inspirational mental
effects of alcohol have been emphasized in many citations from Classical
Antiquity through the Middle Ages and even in modern times. In addition to wine
and beer many alcoholic drinks, such as Champagne, sparkling wines, whisky (or
whiskey), brandy (Cognac) and fruit brandies have a nearly ritual culture of
traditions and customs, without which social life would be unthinkable. The
interplay between enjoyment and displeasure is emphasized in the year 2016 with
the 500-year jubilee of the German purity requirements for beer with countless
events, including the Bavarian State Exhibition 2016. Recently, evidence of a
neuroprotective effect of alcohol was reported with an improvement of
intellectual capacity, which could counteract the widely occurring dementia
syndrome. Millions of people could profit from this effect.
PMID- 27491660
TI - Three dimensional measurement of minimum joint space width in the knee from
stereo radiographs using statistical shape models.
AB - OBJECTIVES: An important measure for the diagnosis and monitoring of knee
osteoarthritis is the minimum joint space width (mJSW). This requires accurate
alignment of the x-ray beam with the tibial plateau, which may not be
accomplished in practice. We investigate the feasibility of a new mJSW
measurement method from stereo radiographs using 3D statistical shape models
(SSM) and evaluate its sensitivity to changes in the mJSW and its robustness to
variations in patient positioning and bone geometry. MATERIALS AND METHODS: A
validation study was performed using five cadaver specimens. The actual mJSW was
varied and images were acquired with variation in the cadaver positioning. For
comparison purposes, the mJSW was also assessed from plain radiographs. To study
the influence of SSM model accuracy, the 3D mJSW measurement was repeated with
models from the actual bones, obtained from CT scans. RESULTS: The SSM-based
measurement method was more robust (consistent output for a wide range of input
data/consistent output under varying measurement circumstances) than the
conventional 2D method, showing that the 3D reconstruction indeed reduces the
influence of patient positioning. However, the SSM-based method showed comparable
sensitivity to changes in the mJSW with respect to the conventional method. The
CT-based measurement was more accurate than the SSM-based measurement (smallest
detectable differences 0.55 mm versus 0. 82 mm, respectively). CONCLUSION: The
proposed measurement method is not a substitute for the conventional 2D
measurement due to limitations in the SSM model accuracy. However, further
improvement of the model accuracy and optimisation technique can be obtained.
Combined with the promising options for applications using quantitative
information on bone morphology, SSM based 3D reconstructions of natural knees are
attractive for further development.Cite this article: E. A. van IJsseldijk, E. R.
Valstar, B. C. Stoel, R. G. H. H. Nelissen, N. Baka, R. van't Klooster, B. L.
Kaptein. Three dimensional measurement of minimum joint space width in the knee
from stereo radiographs using statistical shape models. Bone Joint Res 2016;320
327. DOI: 10.1302/2046-3758.58.2000626.
PMID- 27491661
TI - Cost-Effectiveness of Deep Brain Stimulation for Advanced Parkinson's Disease in
the United States.
AB - OBJECTIVES: Deep brain stimulation (DBS), which uses an implantable device to
modulate brain activity, is clinically superior to medical therapy for treating
advanced Parkinson's disease (PD). We studied the cost-effectiveness of DBS in
conjunction with medical therapy compared to best medical therapy (BMT) alone,
using the latest clinical and cost data for the U.S. healthcare system. MATERIALS
AND METHODS: We used a decision-analytic state-transition (Markov) model to
project PD progression and associated costs for the two treatment strategies. We
estimated the discounted incremental cost-effectiveness ratio (ICER) in U.S.
dollars per quality-adjusted life-year (QALY) from the Medicare payer
perspective, considering a ten-year horizon, and evaluated the robustness of our
projections through extensive deterministic sensitivity analyses. RESULTS: Over
ten years, DBS treatment led to discounted total costs of $130,510 compared to
$91,026 for BMT and added 1.69 QALYs more than BMT, resulting in an ICER of
$23,404 per QALY. This ICER was relatively insensitive to variations in input
parameters, with neurostimulator replacement, costs for DBS implantation, and
costs for treatment of disease-related falls having the greatest effects. Across
all investigated scenarios, including a five-year horizon, ICERs remained under
$50,000 per QALY. Longer follow-up periods and younger treatment age were
associated with greater cost-effectiveness. CONCLUSIONS: DBS is a cost-effective
treatment strategy for advanced PD in the U.S. healthcare system across a wide
range of assumptions. DBS yields substantial improvements in health-related
quality of life at a value profile that compares favorably to other well-accepted
therapies.
PMID- 27491662
TI - Prevalence of impaired glucose tolerance and other types of dysglycaemia among
young twins and singletons in Guinea-Bissau.
AB - BACKGROUND: Twins may be at increased risk of dysglycaemic disorders due to
adverse fetal conditions. Data from Africa regarding this association is limited.
We studied impaired glucose tolerance (IGT) and other types of dysglycemia among
twins and singletons in Guinea-Bissau. METHODS: The study was conducted from
February 2011 until March 2012 at the Bandim Health Project, a health and
demographic surveillance system site in the capital Bissau. Twins (n = 209) and
singletons (n = 182) were recruited from a previously established cohort. Oral
glucose tolerance tests (OGTT) were performed, along with anthropometrics and
collection of clinical and dietary data. RESULTS: Median age was 16.6 and 14.2
years between twins and singletons, respectively (P = 0.08). Mean birth weight
was 2410 vs. 3090 g, respectively (P < 0.001). Twins had higher median fasting-
and two hour capillary plasma glucose, 5.4(3.2-8.2) vs. 5.0(3.2-11.5) mmol/L (P <
0.001) and 6.8(3.4-11.3) vs. 6.2(3.2-12.1) mmol/L (P < 0.001), respectively,
compared to singletons. The prevalence of IGT was 2.5 % (5/209) vs. 3.5 % (6/182)
(RR = 0.73, 95 % CI: 0.20-2.64). 12 % (25/209) of twins had impaired fasting
glucose (IFG), compared to 3.5 % (6/182) of singletons (3.63, 1.53-8.62).
Dysglycemia (IGT and/or IFG or overt diabetes) was found in 17 % (35/209) vs. 9 %
(16/182) (1.90, 1.08-3.37), respectively. CONCLUSIONS: Twins had higher glucose
levels in both the fasting and postprandial state. This may indicate a
detrimental effect of the twin fetal environment on glucose metabolism later in
life, a result contrary to Scandinavian register studies. The IGT burden was low
in this young age group and the risk was similar in twins and singletons.
PMID- 27491663
TI - Electronically delivered, multicomponent intervention to reduce unnecessary
antibiotic prescribing for respiratory infections in primary care: a cluster
randomised trial using electronic health records-REDUCE Trial study original
protocol.
AB - INTRODUCTION: Respiratory tract infections (RTIs) account for about 60% of
antibiotics prescribed in primary care. This study aims to test the
effectiveness, in a cluster randomised controlled trial, of electronically
delivered, multicomponent interventions to reduce unnecessary antibiotic
prescribing when patients consult for RTIs in primary care. The research will
specifically evaluate the effectiveness of feeding back electronic health records
(EHRs) data to general practices. METHODS AND ANALYSIS: 2-arm cluster randomised
trial using the EHRs of the Clinical Practice Research Datalink (CPRD). General
practices in England, Scotland, Wales and Northern Ireland are being recruited
and the general population of all ages represents the target population. Control
trial arm practices will continue with usual care. Practices in the intervention
arm will receive complex multicomponent interventions, delivered remotely to
information systems, including (1) feedback of each practice's antibiotic
prescribing through monthly antibiotic prescribing reports estimated from CPRD
data; (2) delivery of educational and decision support tools; (3) a webinar to
explain and promote effective usage of the intervention. The intervention will
continue for 12 months. Outcomes will be evaluated from CPRD EHRs. The primary
outcome will be the number of antibiotic prescriptions for RTIs per 1000 patient
years. Secondary outcomes will be: the RTI consultation rate; the proportion of
consultations for RTI with an antibiotic prescribed; subgroups of age; different
categories of RTI and quartiles of intervention usage. There will be more than
80% power to detect an absolute reduction in antibiotic prescription for RTI of
12 per 1000 registered patient years. Total healthcare usage will be estimated
from CPRD data and compared between trial arms. ETHICS AND DISSEMINATION: Trial
protocol was approved by the National Research Ethics Service Committee
(14/LO/1730). The pragmatic design of the trial will enable subsequent
translation of effective interventions at scale in order to achieve population
impact. TRIAL REGISTRATION NUMBER: ISRCTN95232781; Pre-results.
PMID- 27491664
TI - Potentially disruptive life events: what are the immediate impacts on chronic
disease management? A case-crossover analysis.
AB - OBJECTIVE: To explore the association between unexpected potentially disruptive
life events in a patient or family member that may challenge an individual's
ability to take medications as prescribed and the discontinuation of evidence
based medications for common, chronic conditions. Understanding the relationship
between medication adherence and life stressors, especially those that can be
identified using administrative data, may help identify patients at risk of non
adherence. DESIGN: Observational self-controlled case-crossover design. SETTING:
Individuals in a nationally representative US commercial health insurance
database. PARTICIPANTS: Adult individuals who initiated an oral hypoglycaemic,
antihypertensive and/or statin and subsequently stopped the medication for >=90
days. MAIN OUTCOME MEASURE: Potentially disruptive life events among patients and
their family members measured in the 30 days just before the medication was
discontinued ('hazard period') compared with the 30 days before this period
('control period'). These events included personal injury, hospitalisation,
emergency room visits, changes in insurance coverage, acute stress or acute
anxiety. RESULTS: Among the 326 519 patients meeting study criteria who
discontinued their chronic disease medications, 88 896 (27.2%) experienced at
least one potentially disruptive life event. Newly experiencing an injury (OR:
1.26, 95% CI 1.12 to 1.42), an emergency room visit (OR: 1.19, 95% CI 1.13 to
1.26) and acute stress (OR: 1.19, 95% CI 1.08 to 1.31) were associated with
discontinuation. Life events among patients' family members did not appear to be
associated with medication discontinuation or occurred less frequently just prior
to discontinuation. CONCLUSIONS: Potentially disruptive life events among
individuals identified using routinely collected claims data are associated with
discontinuation of chronic disease medications. Awareness of these events may
help providers or payers identify patients at risk of non-adherence to maximise
patient outcomes.
PMID- 27491665
TI - Protocol for a national blood transfusion data warehouse from donor to recipient.
AB - INTRODUCTION: Blood transfusion has health-related, economical and safety
implications. In order to optimise the transfusion chain, comprehensive research
data are needed. The Dutch Transfusion Data warehouse (DTD) project aims to
establish a data warehouse where data from donors and transfusion recipients are
linked. This paper describes the design of the data warehouse, challenges and
illustrative applications. STUDY DESIGN AND METHODS: Quantitative data on blood
donors (eg, age, blood group, antibodies) and products (type of product,
processing, storage time) are obtained from the national blood bank. These are
linked to data on the transfusion recipients (eg, transfusions administered,
patient diagnosis, surgical procedures, laboratory parameters), which are
extracted from hospital electronic health records. APPLICATIONS: Expected
scientific contributions are illustrated for 4 applications: determine risk
factors, predict blood use, benchmark blood use and optimise process efficiency.
For each application, examples of research questions are given and analyses
planned. CONCLUSIONS: The DTD project aims to build a national, continuously
updated transfusion data warehouse. These data have a wide range of applications,
on the donor/production side, recipient studies on blood usage and benchmarking
and donor-recipient studies, which ultimately can contribute to the efficiency
and safety of blood transfusion.
PMID- 27491666
TI - Ethnographic process evaluation of a quality improvement project to improve
transitions of care for older people.
AB - OBJECTIVES: Quality improvement projects to address transitions of care across
care boundaries are increasingly common but meet with mixed success for reasons
that are poorly understood. We aimed to characterise challenges in a project to
improve transitions for older people between hospital and care homes. DESIGN:
Independent process evaluation, using ethnographic observations and interviews,
of a quality improvement project. SETTING AND PARTICIPANTS: An English hospital
and two residential care homes for older people. DATA: 32 hours of non
participant observations and 12 semistructured interviews with project members,
hospital and care home staff. RESULTS: A hospital-based improvement team sought
to reduce unplanned readmissions from residential care homes using interventions
including a community-based geriatric team that could be accessed directly by
care homes and a communication tool intended to facilitate transfer of
information between homes and hospital. Only very modest (if any) impacts of
these interventions on readmission rates could be detected. The process
evaluation identified multiple challenges in implementing interventions and
securing improvement. Many of these arose because of lack of consensus on the
nature of the problem and the proper solutions: while the hospital team was keen
to reduce readmissions and saw the problems as lying in poor communication and
lack of community-based support for care homes, the care home staff had different
priorities. Care home staff were unconvinced that the improvement interventions
were aligned with their needs or addressed their concerns, resulting in
compromised implementation. CONCLUSIONS: Process evaluations have a valuable role
in quality improvement. Our study suggests that a key task for quality
improvement projects aimed at transitions of care is that of developing a shared
view of the problem to be addressed. A more participatory approach could help to
surface assumptions, interpretations and interests and could facilitate the
coproduction of solutions. This finding is likely to have broader applicability.
PMID- 27491667
TI - Attitudes and factors affecting acceptability of self-administered cervicovaginal
sampling for human papillomavirus (HPV) genotyping as an alternative to Pap
testing among multiethnic Malaysian women.
AB - OBJECTIVE: The objective of this study was to determine the attitudes and
acceptability of self-administered cervicovaginal sampling compared with
conventional physician-acquired Papanicolaou (Pap) smear among multiethnic
Malaysian women. METHOD: A cross-sectional study was carried out via interviewer
administered surveys from August 2013 through August 2015 at five government-run,
urban health clinics in the state of Selangor. Subjects were participants from an
ongoing community-based human papillomavirus (HPV) prevalence study who answered
a standard questionnaire before and after self-sampling. The cervicovaginal self
sampling for HPV genotyping was performed using a simple brush ('Just for Me';
Preventive Oncology International, Hong Kong). Detailed data on
sociodemographics, previous Pap smear experience, and attitudes towards self
administered cervicovaginal sampling were collected and analysed. Acceptability
was inferred using a five-item Likert scale that included six different
subjective descriptives: experience, difficulty, convenience, embarrassment,
discomfort or pain, and confidence in collecting one's own sample. RESULTS: Of
the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese
and 2.5% from other ethnicities. The median age of the participants was 38 years
(IQR 30-48). Some 68.2% of participants indicated a preference for self-sampling
over the Pap test, with 95% indicating willingness to follow-up a positive result
at the hospital. Age, ethnicity and previous Pap test experience were significant
independent factors associated with preference for self-sampling. The older the
individual, the less likely they were to prefer self-sampling (adjusted OR 0.94,
95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling
(72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004).
Participants who had never undergone a Pap smear were also more likely to prefer
self-sampling (88.5%) than women who had undergone a previous Pap (80.9%)
(adjusted OR 0.06, 95% CI 0.35 to 0.87). CONCLUSIONS: Overall, urban Malaysian
women from multiethnic backgrounds found self-sampling to be an acceptable
alternative to Pap smear.
PMID- 27491668
TI - Effectiveness and cost-effectiveness of the Salut Programme: a universal health
promotion intervention for parents and children-protocol of a register-based
retrospective observational study.
AB - INTRODUCTION: There is inadequate evidence for the effectiveness and cost
effectiveness of health promotion interventions. The Salut Programme aims to
reach all parents and children in the Vasterbotten County of Sweden with a
combination of health promotion interventions initiated during pregnancy and
continued over the childhood period. This study protocol describes an
effectiveness study and an economic evaluation study, where the ongoing Salut
Programme is compared to care-as-usual over the periods of pregnancy, delivery
and the child's first 2 years of life. METHODS: A register-based retrospective
observational study design will be used with existing data sources with respect
to exposures and outcomes. Outcomes of interest are clustered at 3 points: around
the child's birth, 1 month after the child's birth and 2 years after the child's
birth. We will simulate an experiment by retrospectively identifying and
comparing children and their parents in the geographical areas where the Salut
Programme was implemented since 2006 and onwards, and the areas where the
Programme was not implemented before 2009. Outcomes will be analysed and compared
for the premeasure period, and the postmeasure period for both groups. Our
analysis combines difference-in-difference estimation with matching. A
complementary analysis will be carried out on the longitudinal subsample of
mothers who gave birth at least once during each of the time periods. The
economic evaluation aims to capture the wider societal costs and benefits of the
Salut Programme for the first 2 years of the children's lives. Incremental costs
will be compared with incremental health gains and the results will be presented
as a cost-consequence analysis. ETHICS AND DISSEMINATION: The Regional Ethical
Review Board in Umea has given clearance for the Salut Programme research (2010
63-31M). No individual's identity will be revealed when presenting results. This
study will provide information that can guide decision-makers to allocate
resources optimally.
PMID- 27491669
TI - Study design for a randomised controlled trial to explore the modality and
mechanism of Tai Chi in the pulmonary rehabilitation of chronic obstructive
pulmonary disease.
AB - INTRODUCTION: Although pulmonary rehabilitation (PR) is associated with
significant clinical benefits in chronic obstructive pulmonary disease (COPD) and
has been recommended by guidelines, PR with conventional exercise training has
not been widely applied in the clinic because of its inherent limitations.
Alternative exercise such as Tai Chi has been investigated and the results are
promising. However, the strengths and weaknesses of the exercise modality of Tai
Chi, conventional PR and a combination of Tai Chi and conventional PR and the
possible mechanisms underlying Tai Chi exercise remain unclear. This study aims
to address the above research gaps in a well-designed clinical trial. METHODS AND
ANALYSIS: This study is a single-blind, randomised controlled trial. Participants
with stable COPD will be recruited and randomly assigned to one of four groups
receiving Tai Chi exercise, conventional PR using a total body recumbent stepper
(TBRS), combined Tai Chi and TBRS, or usual care (control) in a 1:1:1:1 ratio.
Participants will perform 30 min of supervised exercise three times a week for 8
weeks; they will receive sequential follow-ups until 12 months after recruitment.
The primary outcome will be health-related quality of life as measured by the St
George's Respiratory Questionnaire. Secondary outcomes will include 6 min walking
distance, pulmonary function, the modified Medical Research Council Dyspnoea
Scale, the COPD Assessment Test, the Hospital Anxiety and Depression Scale, the
Berg Balance Scale, exacerbation frequency during the study period, and systemic
inflammatory and immune markers. ETHICS AND DISSEMINATION: Ethics approval has
been granted by the Clinical Trial and Biomedical Ethics Committee of West China
Hospital of Sichuan University (No TCM-2015-82). Written informed consent will be
obtained from each participant before any procedures are performed. The study
findings will be published in peer-reviewed journals and presented at national
and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006874;
Pre-results.
PMID- 27491670
TI - Investigating the accuracy of parentally reported weights and lengths at 12
months of age as compared to measured weights and lengths in a longitudinal
childhood genome study.
AB - BACKGROUND: Childhood obesity studies rely on parentally reported
anthropometrics. However, the accuracy of such data has not been evaluated for 12
month-old children. Moreover, methods to improve the accuracy of reported data
have not been assessed in prior studies. METHODS: A total of 185 children
enrolled in a northern Virginia childhood longitudinal cohort genomic study had
parentally completed surveys at 12 months. Measured weights and lengths were
recorded for the same children from their 12-month paediatrician visit. Weight
for length percentiles were calculated using World Health Organization gender
specific growth charts. The agreement between reported and measured values was
examined using Pearson's correlation, paired t-test and kappa statistics. The
interquartile outlier rule was used to detect and remove outliers. RESULTS:
Parentally reported weight was strongly associated with measured weight at 12
months (r=0.90). There was only a moderate correlation between parentally
reported and measured lengths (r=0.52) and calculated weight for length
percentiles (r=0.65). After removing outliers from parentally reported data,
there was an increase in correlation between parentally reported and measured
data for weight (r=0.93), length (r=0.69) and weight for length percentiles
(r=0.76). Outliers removed compared to all children included were more likely to
have maternal education less than a bachelor's degree (p=0.007). CONCLUSIONS:
After removal of outliers from reported data, there is a strong correlation
between calculated reported and measured weight for length percentiles suggesting
that this may be an effective method to increase accuracy when conducting large
scale obesity studies in young children where study costs benefit from using
parentally reported data.
PMID- 27491671
TI - Study protocol: first nationwide comparative audit of acute lower
gastrointestinal bleeding in the UK.
AB - INTRODUCTION: Acute lower gastrointestinal bleeding (LGIB) is a common indication
for emergency hospitalisation worldwide. In contrast to upper GIB, patient
characteristics, modes of investigation, transfusion, treatment and outcomes are
poorly described. There are minimal clinical guidelines to inform care pathways
and the use of endoscopy, including (diagnostic and therapeutic yields),
interventional radiology and surgery are poorly defined. As a result, there is
potential for wide variation in practice and clinical outcomes. METHODS AND
ANALYSIS: The UK Lower Gastrointestinal Bleeding Audit is a large nationwide
audit of adult patients acutely admitted with LGIB or those who develop LGIB
while hospitalised for another reason. Consecutive, unselected presentations with
LGIB will be enrolled prospectively over a 2-month period at the end of 2015 and
detailed data will be collected on patient characteristics, comorbidities, use of
anticoagulants, transfusion, timing and modalities of diagnostic and therapeutic
procedures, clinical outcome, length of stay and mortality. These will be audited
against predefined minimum standards of care for LGIB. It is anticipated that
over 80% of all acute hospitals in England and some hospitals in Scotland, Wales
and Northern Ireland will participate. Data will be collected on the availability
and organisation of care, provision of diagnostic and therapeutic GI endoscopy,
interventional radiology, surgery and transfusion protocols. ETHICS AND
DISSEMINATION: This audit will be conducted as part of the national comparative
audit programme of blood transfusion through collaboration with specialists in
gastroenterology, surgery and interventional radiology. Individual reports will
be provided to each participant site as well as an overall report and
disseminated through specialist societies. Results will also be published in peer
reviewed journals. The study has been funded by National Health Services (NHS)
Blood and Transplant and the Bowel Disease Research Foundation and endorsed by
the Association of Coloproctology of Great Britain and Ireland.
PMID- 27491672
TI - Patterns of cancer screening, incidence and treatment disparities in China:
protocol for a population-based study.
AB - INTRODUCTION: Cancer has become the leading cause of death in China. Several
knowledge gaps exist with respect to the patterns of cancer care and disparities
in China. Chinese healthcare researchers do not have access to cancer research
data of high quality. Only cancer incidence and mortality rates have been
analysed in China while the patterns of cancer screening and treatment and
disparities have not been rigorously examined. Potential disparities in cancer
care by socioeconomic status have not been analysed in the previous literature.
Population-based estimates of cancer care costs remain unexamined in China. This
project will depict the pattern of cancer screening, incidence and treatment in
Shandong province and enhance our understanding of causes of disparities in
cancer control. METHODS AND ANALYSIS: We will create the first linked database of
cancer registry and health insurance claims in China. We obtained cancer registry
data on breast, gastrointestinal and lung cancer incidence from 2011 to 2014 and
their health insurance claims information from 6 cities/counties of 10.63 million
population and validated it with hospital discharge data. A 1600 participant
survey will be administered to collect additional information of patients'
socioeconomic status, employment and cancer care costs. Frequency analysis,
spatial data exploratory analysis, multivariate logistic regression with
instrumental variable, generalised linear regression and subgroup analysis will
be used to analyse the following: the receipt of cancer screening, stage at
diagnosis, guideline-concordant treatment and cancer care costs. Patient
characteristics, tumour features, hospital characteristics, patient comorbidities
and county-level descriptors will be used as covariates in the multivariate
analysis. ETHICS AND DISSEMINATION: The Institutional Review Board of the School
of Public Health of Shandong University approved this study (20140201). Data
compiled from this project will be made available to all Chinese healthcare
researchers. Study results will be disseminated through peer-reviewed
publications and presentations at national and international meetings.
PMID- 27491673
TI - A Contemporary Approach to Pulmonary Arterial Hypertension.
AB - In recent years, there have been major changes in the landscape of pulmonary
arterial hypertension therapy with the introduction of novel agents and
innovative treatment strategies for this progressive disease. The aim of this
review is to discuss the evolution in trial design in this field and highlight
the salient features of recently published studies. We also summarize our
approach to therapy selection in this chronic disease and identify areas for
future exploration. The therapeutic armamentarium now includes 13 approved
therapies. While most of these agents have been studied in small, short-term
trials using the 6-min walk distance as a primary endpoint, there has been a
shift in recent years toward larger, long-term, event-driven trials that utilize
combined morbidity and mortality endpoints. The SERAPHIN and GRIPHON trials were
two such studies, which led to the approval of the dual endothelin-receptor
antagonist macitentan and the selective prostacyclin receptor antagonist
selexipag, respectively. Other event-driven trials, like AMBITION and COMPASS-2,
have provided valuable insight into the use of combined oral therapies in
symptomatic patients. In conclusion, despite being a more manageable disease in
the modern treatment era, pulmonary hypertension is still associated with
considerable morbidity and much more work remains to be done in this field.
Important questions remain about the most optimal way to manage patients and
conduct trials going forward.
PMID- 27491675
TI - EXPANDING EVIDENCE-BASED TECHNOLOGY ASSESSMENT FOR COVERAGE IN WASHINGTON STATE.
AB - OBJECTIVES: We describe a new evidence-based method for screening and evaluating
emerging medical technologies. Washington State agencies, under legislative
direction, have granted authority to its agency Medical Directors and policy
leaders to make coverage decisions on medical technologies using a "dossier"
process. The dossier process is employed when technology advocates or
manufacturers request Washington State healthcare purchasers to pay for new and
emerging technologies. This offers the advocate an opportunity to submit
scientific evidence and information classically associated with a more formal
health technology assessment. METHODS: The submitted information is independently
reviewed and summarized for Washington State's public healthcare purchasers
allowing a more standardized coverage decision for all public purchasers in
Washington State. RESULTS: This process has allowed Washington State to make
twelve evidence-based coverage decisions at a fraction of the cost of classic
technology assessment. To date, of twelve reviews over 6 years, one health
technology was approved for coverage, ten were not covered and one did not
require a coverage decision. CONCLUSIONS: This evidence-based dossier process has
yielded high-value coverage decisions of new and emerging medical technologies
for public healthcare purchasers in Washington State.
PMID- 27491674
TI - The assessment of depression in people with multiple sclerosis: a systematic
review of psychometric validation studies.
AB - BACKGROUND: The prevalence of depression in people with multiple sclerosis (PwMS)
is high; however, symptoms common to both conditions makes measurement difficult.
There is no high quality overview of validation studies to guide the choice of
depression inventory for this population. METHODS: A systematic review of studies
validating the use of generic depression inventories in people with MS was
conducted using MEDLINE and PsycINFO. Studies validating the use of depression
inventories in PwMS and published in English were included; validation studies of
tests for cognitive function and general mental health were excluded. Eligible
studies were then quality assessed using the COSMIN checklist and findings
synthesised narratively by instrument and validity domain. RESULTS: Twenty-one
studies (N = 5,991 PwMS) evaluating 12 instruments were included in the review.
Risk of bias varied greatly between instrument and validity domain. CONCLUSIONS:
The review of validation studies was constrained by poor quality reporting and
outcome reporting bias. Well-conducted evaluations of some instruments are
unavailable for some validity domains. This systematic review provides an
evidence base for trade-offs in the selection of an instrument for assessing self
reported symptoms of depression in research or clinical practice involving people
with MS. We make detailed and specific recommendations for where further research
is needed. TRIAL REGISTRATION: PROSPERO CRD42014010597.
PMID- 27491677
TI - Educational attainment, gender and health inequalities among older adults in
Catalonia (Spain).
AB - BACKGROUND: Health expectancies vary worldwide according to socioeconomic status
(SES), with health disadvantages being evident among lower SES groups. Using
educational attainment as a proxy of SES, we seek to identify trends in SES
differentials in health by gender, with a particular focus on individuals with
low educational attainment in the adult Catalan population (Spain) aged 55 or
older. METHODS: Using cross-sectional data for 1994 and 2010-2014 drawn from the
Catalan Health Survey, we examined three health indicators to document social
health inequalities: self-perceived health, functional limitations, and
restrictions on activities of daily living (ADL). We applied logistic models for
each indicator, controlling for sociodemographic characteristics, health coverage
and health behaviours. RESULTS: Among the less-educated, females presented a
greater improvement in their self-perceived health over time than did their male
counterparts, there being no significant variations among the medium/high
educated. Regardless of education, males showed an increase in the prevalence of
functional problems (as did the women, but the increase was not statistically
significant). Both genders presented a higher prevalence of limitations when
performing ADL in the second time period. The gender health gap was reduced
slightly both for the low and the medium/high educated, expect in the case of ADL
restrictions. Health and functioning differences by education level persisted,
but showed significant signs of reduction. CONCLUSIONS: Less-educated females
constitute the most disadvantaged group in terms of health and personal autonomy,
though there are encouraging signs that the gap is closing both in terms of
gender and level of education. Health policymakers need to devote particular
attention to the aging population with low SES, especially to women. Public
programmes promoting greater protection and equity, while fostering preventive
and healthy practices, need to target the most underprivileged.
PMID- 27491678
TI - Oestrous sheep serum balances ROS levels to supply in vitro capacitation of ram
spermatozoa.
AB - Reactive oxygen species (ROS) are fundamental for intracellular signalling. In
spermatozoa, they are involved both to apoptosis and to capacitation, and changes
in ROS levels can alter the balance between these two processes. Oestrous sheep
serum (OSS) is considered an efficient agent for in vitro capacitation of ram
spermatozoa. We have explored the effects of OSS on ram sperm physiology,
especially on ROS production, during in vitro capacitation. Semen samples from 15
rams were cryopreserved. After thawing, samples were submitted to four
treatments: control (CTL), 10% OSS supplementation for in vitro sperm
capacitation, caspase inhibitor (INH, Z-VAD-FMK 100 MUM) and OSS (10%) plus
caspase inhibitor (I + E). Sperm samples were incubated for 30 min at 38.5
degrees C and 5% CO2 and evaluated motility and kinetic parameters by computer
assisted semen analysis (CASA) and viability (propidium iodide), apoptotic-like
membrane changes (YO-PRO-1), acrosomal status (PNA-FITC), intracellular calcium
(FLUO-3), membrane fluidity (M540) and ROS production (CM-H2 DCFDA) by flow
cytometry. OSS induced changes in kinetic parameters compatible with
capacitation, with a decrease in the percentage of progressive motility and
linearity, and an increase in the amplitude of the lateral displacement of the
sperm head (p < .05). Moreover, OSS increased the proportion of M540+ viable
spermatozoa, YO-PRO-1+ and acrosome-reacted spermatozoa (p < .05). After
incubation, OSS and I+E achieved lower ROS levels (p < .05). Ca(2+) levels did
not change with the incubation, but were slightly higher (p < .05) when both OSS
and the inhibitor were present. We suggest that OSS may modulate ROS levels,
allowing intracellular signalling for capacitation to occur while preventing
higher levels that could trigger apoptosis.
PMID- 27491679
TI - Dual promoters of the major catalase (KatA) govern distinct survival strategies
of Pseudomonas aeruginosa.
AB - KatA is the major catalase required for hydrogen peroxide (H2O2) resistance and
acute virulence in Pseudomonas aeruginosa PA14, whose transcription is driven
from the promoter (katAp1) located at 155 nucleotide (nt) upstream of the start
codon. Here, we identified another promoter (katAp2), the +1 of which was mapped
at the 51 nt upstream of the start codon, which was responsible for the basal
transcription during the planktonic culture and down-regulated upon H2O2
treatment under the control by the master regulator of anaerobiosis, Anr. To
dissect the roles of the dual promoters in conditions involving KatA, we created
the promoter mutants for each -10 box (p1m, p2m, and p1p2m) and found that katAp1
is required for the function of KatA in the logarithmic growth phase during the
planktonic culture as well as in acute virulence, whereas katAp2 is required for
the function of KatA in the stationary phase as well as in the prolonged biofilm
culture. This dismantling of the dual promoters of katA sheds light on the roles
of KatA in stress resistance in both proliferative and growth-restrictive
conditions and thus provides an insight into the regulatory impacts of the major
catalase on the survival strategies of P. aeruginosa.
PMID- 27491680
TI - Post-translocational adaptation drives evolution through genetic selection and
transcriptional shift in Saccharomyces cerevisiae.
AB - Adaptation by natural selection might improve the fitness of an organism and its
probability to survive in unfavorable environmental conditions. Decoding the
genetic basis of adaptive evolution is one of the great challenges to deal with.
To this purpose, Saccharomyces cerevisiae has been largely investigated because
of its short division time, excellent aneuploidy tolerance and the availability
of the complete sequence of its genome with a thorough genome database. In the
past, we developed a system, named bridge-induced translocation, to trigger
specific, non-reciprocal translocations, exploiting the endogenous recombination
system of budding yeast. This technique allows users to generate a heterogeneous
population of cells with different aneuploidies and increased phenotypic
variation. In this work, we demonstrate that ad hoc chromosomal translocations
might induce adaptation, fostering selection of thermo-tolerant yeast strains
with improved phenotypic fitness. This "yeast eugenomics" correlates with a shift
to enhanced expression of genes involved in stress response, heat shock as well
as carbohydrate metabolism. We propose that the bridge-induced translocation is a
suitable approach to generate adapted, physiologically boosted strains for
biotechnological applications.
PMID- 27491681
TI - BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells.
AB - Schwann cell (SC) myelination is pivotal for the proper physiological functioning
of the nervous system, but the underlying molecular mechanism remains less well
understood. Here, we showed that the expression of bone morphogenetic protein 7
(BMP7) inversely correlates with myelin gene expression during peripheral
myelination, which suggests that BMP7 is likely a negative regulator for myelin
gene expression. Our experiments further showed that the application of BMP7
attenuates the cAMP induced myelin gene expression in SCs. Downstream pathway
analysis suggested that both p38 MAPK and SMAD are activated by exogenous BMP7 in
SCs. The pharmacological intervention and gene silence studies revealed that p38
MAPK, not SMAD, is responsible for BMP7-mediated suppression of myelin gene
expression. In addition, c-Jun, a potential negative regulator for peripheral
myelination, was up-regulated by BMP7. In vivo experiments showed that BMP7
treatment greatly impaired peripheral myelination in newborn rats. Together, our
results established that BMP7 is a negative regulator for peripheral myelin gene
expression and that p38 MAPK/c-Jun axis might be the main downstream target of
BMP7 in this process.
PMID- 27491682
TI - Prefrontal activity decline in women under a single dose of diazepam during rule
guided responses: an fMRI study.
AB - Daily life events confront us with new situations demanding responses to usual
and unusual rules. Diazepam (DZ), a clinically important drug, facilitates the
inhibitory activity of the GABAergic system. Prefrontal cortex, rich in DZ
receptors, coordinates necessary resources to direct actions according to rules.
The balance between excitatory and inhibitory activity is critical to achieve
optimal function of brain systems leading to complex functions. Major sex
differences in the physiological mechanisms of the GABAergic system have been
reported. However, the differential influence of DZ on men and women in neural
activity during behavior directed by frontal lobes remains unexplored. The
ability of healthy volunteers to select responses following usual/congruent and
novel/incongruent rules, and brain correlates were measured with fMRI under the
administration of DZ and a placebo. 10 mg of DZ was enough to decrease the
performance in a different manner between men and women. While reaction times
increased in both men and women, women committed more errors selecting responses
than men under DZ. Men demonstrated increased activity, while women demonstrated
decreased activity in frontal regions involved in response selection of rules.
These findings could have important consequences in understanding the
differential influences of DZ between the sexes in complex daily life situations.
More importantly, this study emphasizes the importance of understanding the
differential effects on men and women of drugs widely employed by society,
thereby achieves better therapeutic results and avoids side effects that the
present study revealed to be different between sexes.
PMID- 27491683
TI - Evidence of impaired neuromuscular responses in the support leg to a
destabilizing swing phase perturbation in hemiparetic gait.
AB - The neuromuscular mechanisms that underlie post-stroke impairment in reactive
balance control during gait are not fully understood. Previous research has
described altered muscle activations in the paretic leg in response to postural
perturbations from static positions. Additionally, attenuation of interlimb
reflexes after stroke has been reported. Our goal was to characterize post-stroke
changes to neuromuscular responses in the stance leg following a swing phase
perturbation during gait. We hypothesized that, following a trip, altered timing,
sequence, and magnitudes of perturbation-induced activations would emerge in the
paretic and nonparetic support legs of stroke survivors compared to healthy
control subjects. The swing foot was interrupted, while subjects walked on a
treadmill. In healthy subjects, a sequence of perturbation-induced activations
emerged in the contralateral stance leg with mean onset latencies of 87-147 ms.
The earliest latencies occurred in the hamstrings and hip abductor and adductors.
The hamstrings, the adductor magnus, and the gastrocnemius dominated the relative
balance of perturbation-induced activations. The sequence and balance of
activations were largely preserved after stroke. However, onset latencies were
significantly delayed across most muscles in both paretic and nonparetic stance
legs. The shortest latencies observed suggest the involvement of interlimb
reflexes with supraspinal pathways. The preservation of the sequence and balance
of activations may point to a centrally programmed postural response that is
preserved after stroke, while post-stroke delays may suggest longer transmission
times for interlimb reflexes.
PMID- 27491684
TI - Biosecurity for Translocations: Cirl Bunting (Emberiza cirlus), Fisher's
Estuarine Moth (Gortyna borelii lunata), Short-Haired Bumblebee (Bombus
subterraneus) and Pool Frog (Pelophylax lessonae) Translocations as Case Studies.
AB - Exposure to parasites in conservation translocations increases the risks to
recipient and translocated populations from disease, and therefore there has been
interest in implementing biosecurity methods. Using four case examples we
described how biosecurity was applied in practical translocation scenarios prior
to and during a translocation and also post-release. We implemented biosecurity,
including quarantine barriers, at specific points in the translocation pathway
where hazards, identified by the disease risk analysis, had the potential to
induce disease. Evidence that biosecurity protected translocated and recipient
populations, included an absence of mortality associated with high-risk non
native parasites, a reduction in mortality associated with endemic parasites, the
absence of high-risk pathogenic parasites, or associated diseases, at the
destination; and the apparent absence of diseases in closely related species at
the destination site. The biosecurity protocols did not alter the level or
duration of translocated species confinement and therefore probably did not act
as a stressor. There is a monetary cost involved in biosecurity but the
epidemiological evidence suggests that conservation translocation managers should
carefully consider its use. Breakdowns in quarantine have occurred in human
hospitals despite considerable investment and training for health professionals,
and we therefore judge that there is a need for training in the objectives and
maintenance of quarantine barriers in conservation translocations. Biosecurity
protocols for conservation translocations should be continually updated in
response to findings from disease risk analysis and post-release disease
surveillance and we recommend further studies to evaluate their effectiveness.
PMID- 27491685
TI - Laparoscopic Versus Open Resection for Gastrointestinal Stromal Tumors (GISTs).
AB - PURPOSE: Primary gastrointestinal stromal tumors (GISTs) are typically treated
with open resection. There is growing interest in laparoscopic GIST resection;
however, data is limited. We report our experience with GIST resections using
both open and laparoscopic techniques. MATERIALS AND METHODS: Twenty-nine GIST
patients underwent definitive intent resection at the University of Missouri from
1990 to 2010. Patients who underwent laparoscopic resection (n = 7) were matched
on the basis of tumor size, age, tumor location, and National Comprehensive
Cancer Network (NCCN) risk stratification with seven patients who underwent open
resection. The two groups were compared with respect to age, gender, BMI, tumor
size, tumor site, mitotic rate, surgical margins, NCCN risk stratification,
estimated blood loss, hospital stay, surgical complications, disease recurrence,
and overall survival. RESULTS: The cohorts did not differ with respect to age,
gender, BMI, tumor location, tumor size, or positive margins (p > 0.05). Patients
who underwent open resection had more NCCN high-risk patients, but the difference
was not statistically significant (p = 0.08). There was significantly less
estimated blood loss (median 15 vs. 150 mL, p < 0.05) and significantly shorter
hospital stay (median 4 vs. 7 days, p < 0.05) for the laparoscopy group. There
were no recurrences in the laparoscopy group, but there was one in the open group
with a median follow-up of 55 and 63 months, respectively (p > 0.05). Five-year
disease-free survival was 100 % for the laparoscopic group and 83 % for the open
resection group. CONCLUSIONS: Laparoscopic resection for appropriately selected
GISTs is feasible and associated with significantly less blood loss and shorter
hospitalizations compared to open resection. Further studies are needed to better
define its role for GIST.
PMID- 27491686
TI - Integrated plasmonic circuitry on a vertical-cavity surface-emitting
semiconductor laser platform.
AB - Integrated plasmonic sources and detectors are imperative in the practical
development of plasmonic circuitry for bio- and chemical sensing, nanoscale
optical information processing, as well as transducers for high-density optical
data storage. Here we show that vertical-cavity surface-emitting lasers (VCSELs)
can be employed as an on-chip, electrically pumped source or detector of
plasmonic signals, when operated in forward or reverse bias, respectively. To
this end, we experimentally demonstrate surface plasmon polariton excitation,
waveguiding, frequency conversion and detection on a VCSEL-based plasmonic
platform. The coupling efficiency of the VCSEL emission to waveguided surface
plasmon polariton modes has been optimized using asymmetric plasmonic
nanostructures. The plasmonic VCSEL platform validated here is a viable solution
for practical realizations of plasmonic functionalities for various applications,
such as those requiring sub-wavelength field confinement, refractive index
sensitivity or optical near-field transduction with electrically driven sources,
thus enabling the realization of on-chip optical communication and lab-on-a-chip
devices.
PMID- 27491688
TI - Different effects of BCG strains - A natural experiment evaluating the impact of
the Danish and the Russian BCG strains on morbidity and scar formation in Guinea
Bissau.
AB - BACKGROUND: Different Bacillus Calmette-Guerin (BCG) vaccine strains may have
different non-specific effects. We assessed the effect of two BCG strains (Danish
and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau.
METHODS: During 2011-2013, infants in the Bandim Health Project's urban study
area received the Danish or Russian BCG in a natural experiment. Health center
consultations were registered at point of care and scar status and size at age
41/2 months. We assessed the effect of strain on consultation rates between
vaccination and age 45days in Cox proportional hazards models. Scar prevalence
and size were compared using binomial regression and ranksum tests. RESULTS:
Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991).
The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for
Danish BCG compared with Russian BCG. Girls vaccinated with Danish BCG tended to
have lower consultation rates compared with girls vaccinated with Russian BCG
(aHR 0.56 (0.25-1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74
2.11)), p=0.09. Children vaccinated with Danish BCG were more likely to develop a
scar (97%) than children vaccinated with Russian BCG (87%), the relative risk
(RR) being 1.11 (1.06-1.16). The effect was stronger in girls, and BCG scar size
was larger among infants vaccinated with the Danish strain. CONCLUSION: BCG
strain influences scar prevalence and scar size, and may have sex differential
effects on morbidity. BCG strains are currently used interchangeably, but BCG
scarring has been linked to subsequent survival. Hence, more research into the
health effects of different BCG strains is warranted. Small adjustments of BCG
production could potentially lower childhood morbidity and mortality at low cost.
PMID- 27491689
TI - Pathways to preterm birth: Case definition and guidelines for data collection,
analysis, and presentation of immunization safety data.
PMID- 27491687
TI - Neonatal infections: Case definition and guidelines for data collection,
analysis, and presentation of immunisation safety data.
AB - Maternal vaccination is an important area of research and requires appropriate
and internationally comparable definitions and safety standards. The GAIA group,
part of the Brighton Collaboration was created with the mandate of proposing
standardised definitions applicable to maternal vaccine research. This study
proposes international definitions for neonatal infections. The neonatal
infections GAIA working group performed a literature review using Medline, EMBASE
and the Cochrane collaboration and collected definitions in use in neonatal and
public health networks. The common criteria derived from the extensive search
formed the basis for a consensus process that resulted in three separate
definitions for neonatal blood stream infections (BSI), meningitis and lower
respiratory tract infections (LRTI). For each definition three levels of evidence
are proposed to ensure the applicability of the definitions to different
settings. Recommendations about data collection, analysis and presentation are
presented and harmonized with the Brighton Collaboration and GAIA format and
other existing international standards for study reporting.
PMID- 27491690
TI - Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating
oxidative stress in a Parkinson's disease model.
AB - PURPOSE: Oxidative stress is the leading cause in the pathogenesis of Parkinson's
disease. Rutin is a naturally occurring strong antioxidant molecule with wide
therapeutic applications. It suffers from the problem of low oral bioavailability
which is due to its poor aqueous solubility. METHODS: In order to increase the
solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were
prepared. The oil, surfactant and co-surfactant were selected based on
solubility/miscibility studies. Optimization was done by a three-factor, four
level (34) Box-Behnken design. The independent factors were oil, surfactant and
co-surfactant concentration and the dependent variables were globule size, self
emulsification time, % transmittance and cumulative percentage of drug release.
The optimized SNEDDS formulation (RSE6) was evaluated for various release
studies. Antioxidant activity was assessed by various in vitro tests such as 2,2
diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which
had Parkinson's-type symptoms were used to determine the antioxidant potential of
rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning
microscopy. RESULTS: An optimized SNEDDS formulation consisting of Sefsol +
vitamin E-Solutol HS 15-Transcutol P at proportions of 25:35:17.5 (w/w) was
prepared and characterized. The globule size and polydispersity index of the
optimized formulation was found to be 16.08 +/- 0.02 nm and 0.124 +/- 0.01,
respectively. A significant (p < 0.05) increase in the percentage of drug release
was achieved in the case of the optimized formulation as compared to rutin
suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral
bioavailability. The optimized formulation had significant in vitro and in vivo
antioxidant activity. CONCLUSION: Rutin SNEDDS have been successfully prepared
and they can serve as an effective tool in enhancing the oral bioavailability and
efficacy of rutin, thus helping in ameliorating oxidative stress in
neurodegenerative disorders like Parkinson's disease.
PMID- 27491691
TI - Laminins and cancer stem cells: Partners in crime?
AB - As one of the predominant protein families within the extracellular matrix both
structurally and functionally, laminins have been shown to be heavily involved in
tumor progression and drug resistance. Laminins participate in key cellular
events for tumor angiogenesis, cell invasion and metastasis development,
including the regulation of epithelial-mesenchymal transition and basement
membrane remodeling, which are tightly associated with the phenotypic
characteristics of stem-like cells, particularly in the context of cancer. In
addition, a great deal of studies and reports has highlighted the critical roles
of laminins in modulating stem cell phenotype and differentiation, as part of the
stem cell niche. Stemming from these discoveries a growing body of literature
suggests that laminins may act as regulators of cancer stem cells, a tumor cell
subpopulation that plays an instrumental role in long-term cancer maintenance,
metastasis development and therapeutic resistance. The accumulating evidence in
this emerging research area suggests that laminins represent potential
therapeutic targets for anti-cancer treatments against cancer stem cells, and
that they may be used as predictive and prognostic markers to inform clinical
management and improve patient survival.
PMID- 27491692
TI - NF-kappaB activation in chronic lymphocytic leukemia: A point of convergence of
external triggers and intrinsic lesions.
AB - The nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in
chronic lymphocytic leukemia (CLL) patients, and hence plays a major role in
disease development and evolution. In contrast to many other mature B-cell
lymphomas, only a few recurrently mutated genes involved in canonical or non
canonical NF-kappaB activation have been identified in CLL (i.e. BIRC3, MYD88 and
NFKBIE mutations) and often at a low frequency. On the other hand, CLL B cells
seem 'addicted' to the tumor microenvironment for their survival and
proliferation, which is primarily mediated by interaction through a number of
cell surface receptors, e.g. the B-cell receptor (BcR), Toll-like receptors and
CD40, that in turn activate downstream NF-kappaB. The importance of cell
extrinsic triggering for CLL pathophysiology was recently also highlighted by the
clinical efficacy of novel drugs targeting microenvironmental interactions
through the inhibition of BcR signaling. In other words, CLL can be considered a
prototype disease for studying the intricate interplay between external triggers
and intrinsic aberrations and their combined impact on disease evolution. In this
review, we will discuss the current understanding of mechanisms underlying NF
kappaB deregulation in CLL, including micro-environmental, genetic and epigenetic
events, and summarize data generated in murine models resembling human CLL.
Finally, we will also discuss different strategies undertaken to intervene with
the NF-kappaB pathway and its upstream mediators.
PMID- 27491693
TI - A Comparison of Magnetization Transfer Methods to Assess Brain and Cervical Cord
Microstructure in Multiple Sclerosis.
AB - BACKGROUND: Demyelination is a core pathological feature of multiple sclerosis
(MS) and spontaneous remyelination appears to be an important mechanism for
repair in the disease. Magnetization transfer ratio imaging (MTR) has been used
extensively to evaluate demyelination, although limitations to its specificity
are recognized. MT saturation imaging (MTsat) removes some of the T1 dependence
of MTR. We have performed a comparative evaluation of MTR and MTsat imaging in a
mixed group of subjects with active MS, to explore their relative sensitivity to
pathology relevant to explaining clinical outcomes. METHODS: A total of 134
subjects underwent MRI of their brain and cervical spinal cord. Isotropic 3
dimensional pre- and postcontrast T1-weighted and T2-weighted fluid-attenuated
inversion recovery (FLAIR) volumes were segmented into brain normal appearing
white matter (NAWM), brain WM lesions (WML), normal appearing spinal cord (NASC),
and spinal cord lesions. Volumes and metrics for MTR and MTsat histograms were
calculated for each region. RESULTS: Significant Spearman correlations were found
with the Expanded Disability Status Scale and timed 25-foot walk for the whole
brain and WML MTR, but not in that from the NAWM or any cervical spinal cord
region. By contrast, the MTsat was correlated with both disability metrics in all
these regions in both the brain and spine. CONCLUSIONS: This study extends prior
work relating atrophy and lesion load with disability, by characterization of
MTsat parameters. MTsat is practical in routine clinical applications and may be
more sensitive to tissue damage than MTR for both brain and cervical spinal cord.
PMID- 27491694
TI - Neuronal cholesterol metabolism increases dendritic outgrowth and synaptic
markers via a concerted action of GGTase-I and Trk.
AB - Cholesterol 24-hydroxylase (CYP46A1) is responsible for brain cholesterol
elimination and therefore plays a crucial role in the control of brain
cholesterol homeostasis. Altered CYP46A1 expression has been associated with
several neurodegenerative diseases and changes in cognition. Since CYP46A1
activates small guanosine triphosphate-binding proteins (sGTPases), we
hypothesized that CYP46A1 might be affecting neuronal development and function by
activating tropomyosin-related kinase (Trk) receptors and promoting
geranylgeranyl transferase-I (GGTase-I) prenylation activity. Our results show
that CYP46A1 triggers an increase in neuronal dendritic outgrowth and dendritic
protrusion density, and elicits an increase of synaptic proteins in the crude
synaptosomal fraction. Strikingly, all of these effects are abolished by
pharmacological inhibition of GGTase-I activity. Furthermore, CYP46A1 increases
Trk phosphorylation, its interaction with GGTase-I, and the activity of GGTase-I,
which is crucial for the enhanced dendritic outgrowth. Cholesterol
supplementation studies indicate that cholesterol reduction by CYP46A1 is the
necessary trigger for these effects. These results were confirmed in vivo, with a
significant increase of p-Trk, pre- and postsynaptic proteins, Rac1, and
decreased cholesterol levels, in crude synaptosomal fractions prepared from
CYP46A1 transgenic mouse cortex. This work describes the molecular mechanisms by
which neuronal cholesterol metabolism effectively modulates neuronal outgrowth
and synaptic markers.
PMID- 27491695
TI - Long-term Repeatability and Reproducibility of Phosphene Characteristics in
Chronically Implanted Argus II Retinal Prosthesis Subjects.
AB - PURPOSE: Previously published literatures of acute studies on few subjects have
shown contradictory evidence on the reproducibility and characteristics of the
elicited phosphenes, despite using the same stimulating parameters with
epiretinal electrode arrays. In this study, we set out to investigate the long
term repeatilibity and reproducibility of phosphenes in subjects chronically
implanted with the Argus II retinal prosthesis (Second Sight Medical Products,
Inc., Sylmar, CA, USA). DESIGN: Retrospective interventional case series and
reliability study. METHODS: Six Argus II subjects of >5 years implantation from a
single site participated. The 4-electrode cluster ("quad") closest to fovea was
stimulated in each subject with a fixed biphasic current. Perceived phosphenes
were depicted relative to subjective visual field center. The stimulus was
applied at reducing time intervals from 20 minutes to 1 second. Two sets of
stimulations were performed on the same day and 2 further sets repeated on a
separate visit >1 week apart. RESULTS: Each subject depicted phosphenes of
consistent shapes and sizes, and reported seeing the same colors with the fixed
stimulating parameters, irrespective of the interstimuli intervals. However,
there is a wide intersubject variation in the phosphene characteristics. Four
subjects drew phosphenes in the same visual field quadrant, as predicted by the
quad-fovea location. Two subjects depicted phosphenes in the same hemifield as
the expected locations. CONCLUSION: Phosphenes for each subject were consistently
reproducible in all our chronically implanted subjects. This has important
implications in the development of long-term pixelated prosthetic vision for
future devices.
PMID- 27491696
TI - Same-site Trabeculectomy Revision for Failed Trabeculectomy: Outcomes and Risk
Factors for Failure.
AB - PURPOSE: To evaluate long-term tonometric outcomes of same-site trabeculectomy
revision with mitomycin C (MMC) after failure of an initial trabeculectomy, and
to identify risk factors for failure in patients with open-angle glaucoma.
DESIGN: Retrospective cohort study. METHODS: One-hundred and seventeen patients
(130 eyes) with primary open-angle, pseudoexfoliation, or pigmentary glaucoma,
who failed a first trabeculectomy and who were >=40 years of age at the time of
same-site trabeculectomy revision, were included. Three levels of success
criteria were defined: (A) intraocular pressure (IOP) <=18 mm Hg and IOP
reduction of 20%; (B) IOP <=15 mm Hg and IOP reduction of 25%; and (C) IOP <=12
mm Hg and IOP reduction of 30%. The primary outcome was the qualified Kaplan
Meier success rate (with or without medications) for each criterion. Cox
multivariate regression analysis was used to identify risk factors for failure.
RESULTS: The success rates (+/- standard error) at the first, third, and fifth
years of follow-up for criterion A were 69.7% (+/- 4.1%), 58.2% (+/- 4.6%), and
51.1% (+/- 5.0%); for criterion B these were 60.9% (+/- 4.4%), 47.8% (+/- 4.7%),
and 44.0 (+/- 4.8%); and for criterion C, 44.6% (+/- 4.5%), 29.7% (+/- 4.4%), and
25.8% (+/- 4.3%). Mean follow-up was 5.2 (+/- 3.6) years. A time interval between
the first and the same-site trabeculectomy revision of <3 years, worse baseline
visual acuity, and dyslipidemia were significant risk factors for failure.
CONCLUSIONS: Given the long-term tonometric success rates along with significant
medication reduction, same-site trabeculectomy revision with MMC should be
considered as a viable option to achieve reasonable IOP targets after a first
failed trabeculectomy in open-angle glaucoma patients.
PMID- 27491697
TI - Sequential Bilateral Corneal Transplantation and Graft Survival.
AB - PURPOSE: To investigate graft survival and rejection following sequential
bilateral corneal transplantation. DESIGN: Retrospective cohort study. METHODS:
The study included patients with Fuchs endothelial dystrophy (FED), pseudophakic
bullous keratopathy (PBK), or keratoconus who had undergone a penetrating
keratoplasty (PK), endothelial keratoplasty (EK), or deep anterior lamellar
keratoplasty (DALK) between 1999 and 2012. The main cohort included patients who
had received a first transplant in both eyes for the same indication and a
control cohort patients who had undergone a unilateral first corneal transplant.
Main outcome measures were graft rejection or failure at 5 years. RESULTS: A
total of 11 822 patients were included, of whom 9335 had a unilateral and 2487
bilateral corneal transplantation. For patients with FED (P < .005) and KC (P =
.03) but not PBK (P = .19), a transplant in the second eye was associated with a
50% reduction in risk of graft failure within 5 years in the first eye (FED:
hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.34-0.64; KC: HR 0.50, 95%
CI: 0.24-1.02). For FED this was dependent on the type of transplant (EK: HR
0.30, 95% CI: 0.17-0.52; PK: HR 0.61, 95% CI: 0.42-0.88). We found no association
between a transplant in the second eye and a rejection episode in the first eye
(KC P = .19, FED P = .39, PBK P = .19). CONCLUSION: For FED and KC, a transplant
in the second eye was associated with a reduced risk of graft failure in the
first eye, independent of inter-transplant time. For FED this effect was
pronounced following an EK in the first eye, where the risk of failure was
reduced by 70%.
PMID- 27491699
TI - HIV incidence among gay men and other men who have sex with men in 2020: where is
the epidemic heading?
AB - The goal to effectively prevent new HIV infections among gay, bisexual, and other
men who have sex with men (MSM) is more challenging now than ever before. Despite
declines in the late 1990s and early 2000s, HIV incidence among MSM is now
increasing in many low- and high-income settings including the US, with young,
adolescent, and racial/ethnic minority MSM being among those at highest risk.
Potentiating HIV risks across all settings are individual-, network-, and
structural-level factors such as stigma and lack of access to pre-exposure
prophylaxis (PrEP) and antiretroviral treatment as prevention. To make a
sustained impact on the epidemic, a concerted effort must integrate all evidence
based interventions that will most proximally decrease HIV acquisition and
transmission risks, together with structural interventions that will support
improved coverage and retention in care. Universal HIV treatment, increased
access to HIV testing, and daily oral PrEP have emerged as integral to the
prevention of HIV transmission, and such efforts should be immediately expanded
for MSM and other populations disproportionately affected by HIV. Respect for
human rights and efforts to combat stigma and improve access to prevention
services are needed to change the trajectory of the HIV pandemic among MSM.
PMID- 27491698
TI - Localized Changes in Retinal Nerve Fiber Layer Thickness as a Predictor of
Localized Functional Change in Glaucoma.
AB - PURPOSE: To determine how well rates of localized retinal nerve fiber layer
thickness (RNFLT) change correlate with rates of sensitivity change at
corresponding locations in the visual field in glaucoma. DESIGN: Retrospective
cohort study. METHODS: Three hundred and sixty-four eyes of 191 participants with
suspected or confirmed glaucoma, as judged by experienced clinicians, were tested
every 6 months with perimetry and optical coherence tomography (OCT). For each 24
2 visual field location, the corresponding sectoral peripapillary RNFLT was
defined using a 30-degree sector, centered on the angle of nerve fiber entry into
the optic nerve head. Rates of change of pointwise sensitivity and sectoral RNFLT
were calculated over the last 8 visits at which reliable data were obtained.
Passing-Bablok regression was used to predict the rate of pointwise sensitivity
change from the rate of sectoral RNFLT change, for each location. RESULTS: Rates
of sectoral RNFLT change were significantly predictive of rates of pointwise
sensitivity change at all locations in the field. Correlations were modest,
averaging 0.15, ranging from 0.03 to 0.25 depending on the location. A 1 MUm/y
more rapid thinning in corresponding sectors was associated with 0.3 dB/y more
rapid loss in the superior visual field but less than 0.1 dB/y more rapid loss at
many locations in the inferior visual field. CONCLUSIONS: Localized RNFL thinning
is associated with sensitivity loss at corresponding locations in the visual
field, and their rates of change are significantly correlated. Peripapillary
RNFLT may be used to monitor localized changes caused by glaucoma that have
measurable consequences for a patient's vision.
PMID- 27491700
TI - Adverse events related to the new psychoactive substance 3-fluorophenmetrazine -
results from the Swedish STRIDA project.
AB - BACKGROUND: New psychoactive substances (NPS) are often poorly pharmacologically
documented and the production is unregulated, implying high risks for toxic side
effects. This report from the STRIDA project describes analytically confirmed non
fatal intoxications involving the phenmetrazine analogue 3-fluorophenmetrazine (3
FPM). STUDY DESIGN AND METHODS: Observational case series of patients with
suspected acute NPS exposure requiring hospital care. Blood and urine samples
were collected from patients presenting in emergency departments (ED) or
intensive care units (ICU), after consultation with the Swedish Poisons
Information Centre (PIC). Laboratory analysis was performed by multi-component
liquid chromatography-mass spectrometry. Clinical data were collected during PIC
consultations and retrieved from medical records. RESULTS: From November 2014 to
October 2015, eight cases were registered as 3-FPM or "phenmetrazine"
intoxications at the PIC after consultation. During the same period, analysis of
STRIDA project samples confirmed 3-FPM use in a total of 19 patients (84% men)
aged 22-54 (median 30) years. 3-FPM was detected in 15 out of 19 serum (2.7-1416
ng/mL) and in 14 out of 14 urine (1.0-6857 MUg/mmol creatinine) samples. All
patients were also tested positive for other psychoactive substances, with
benzodiazepines being most common (57% of the cases). Ten patients were monitored
in the ED for <4 h, while six needed ICU monitoring of which five were graded as
severe intoxications (Poisoning Severity Score 3). Prominent clinical signs were
tachycardia (47%), depressed consciousness (42%), agitation/anxiety (37%),
delirium (37%), dilated pupils (26%), and seizures (16%). All patients survived.
CONCLUSION: In 19 patients testing positive for 3-FPM, a high incidence of severe
clinical features was demonstrated. However, as all patients had also used other
psychoactive substances, it was difficult to identify a unique toxidrome for 3
FPM. The results further showed that many 3-FPM intoxications would have been
missed, if relying solely on information from PIC consultations. These results
emphasize the importance of performing bioanalytical investigation in cases of
suspected NPS intoxication.
PMID- 27491701
TI - Arbuscular mycorrhizal fungi in the growth and extraction of trace elements by
Chrysopogon zizanioides (vetiver) in a substrate containing coal mine wastes.
AB - Vetiver (Chrysopogon zizanioides) is a fast-growing, high biomass producing plant
employed for environmental rehabilitation. The study evaluated the effects of
arbuscular mycorrhizal fungi (AMF) on the growth and trace element
phytoextracting capabilities of vetiver in a substrate containing coalmine wastes
in Southern Brazil. AMF included Acaulospora colombiana, Acaulospora morrowiae,
Acaulospora scrobiculata, Dentiscutata heterogama, Gigaspora margarita, and
Rhizophagus clarus. Among those, A. colombiana, G. margarita, and R. clarus
promoted higher growth. AMF stimulated average increments in the accumulated P of
82% (roots), 194% (shoots first harvest-90 days) and 300% (shoots second harvest
165 days) and affected the phytoextraction of trace elements by vetiver, with
larger concentrations in the roots. Plants inoculated with A. colombiana, A.
morrowiae, and A. scrobiculata, in addition to the control, presented the highest
levels of Cu and Zn in the roots. Overall, G. margarita stimulated the highest
production of biomass, and, therefore, showed the most significant levels of
trace elements in the plants. This work shows the benefits of certain AMF
(especially A. morrowiae, G. margarita, and R. clarus) for the production of
biomass and P uptake by vetiver, demonstrating the potential of those species for
the rehabilitation of coal-mine-degraded soils.
PMID- 27491702
TI - Secondary ion yields for vacuum-type electrospray droplet beams measured with a
triple focus time-of-flight analyzer.
AB - RATIONALE: We previously developed a massive cluster ion beam gun for secondary
ion mass spectrometry (SIMS) in which the primary beam source is a vacuum
electrospray. The secondary ion yields produced by this method had not yet been
measured with a commercial time-of-flight (TOF) secondary ion mass spectrometer,
and the ionization performance was unknown. METHODS: A vacuum-type electrospray
droplet ion gun was connected to a triple-focus TOF analyzer. The flight time of
the secondary ions was measured using a sample-bias pulsing method, because a
short pulse of the electrospray droplet beam could not be obtained. The secondary
ion yields of an amino acid sample produced by the electrospray droplet beams and
atomic Ga ion beams were compared. RESULTS: TOF secondary ion spectra were
measured for the amino acid and peptide samples with a mass resolution of ~500
using the sample-bias pulsing method. The secondary ion yield of the amino acid
sample produced with the 10 kV vacuum-type electrospray droplet beams was much
higher than that produced by 10 kV Ga ion beams. In addition, the secondary ion
yields for the peptide sample and amino acid samples were almost similar.
CONCLUSIONS: This is the first report on secondary ion yields produced with
vacuum-type electrospray droplet ion beams and measured with a semi-commercial
TOF analyzer. The enhancement of secondary ion yields, in particular for
relatively high-mass molecules, would be very useful in the SIMS analysis of a
wide variety of biological samples. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27491703
TI - Use of clinical practice guidelines by dentists: findings from the Japanese
dental practice-based research network.
AB - RATIONALE, AIMS AND OBJECTIVES: The objectives of this study were to: (1) examine
differences in the use of dental clinical practice guidelines among Japanese
dentists, and (2) identify characteristics associated with the number of
guidelines used by participating dentists. METHODS: We conducted a cross
sectional study consisting of a questionnaire survey in Japan between July 2014
and May 2015. The study queried dentists working in outpatient dental practices
who are affiliated with the Dental Practice-Based Research Network Japan (n =
148). They were asked whether they have used each of 15 Japanese dental clinical
guidelines. Associations between the number of guidelines used by participants
and specific characteristics were analysed via negative binomial regression
analysis. RESULTS: The mean number of guidelines used by participating dentists
was 2.5 +/- 2.9 [standard deviation (SD)]. Rate of use of guidelines showed
substantial variation, from 5% to 34% among dentists. The proportion of dentists
that used guidelines was the highest among oral medicine specialists, who had the
highest proportion for 10 of 15 guidelines. Negative binomial regression analysis
identified three factors significantly associated with the number of guidelines
used: 'years since graduation from dental school', 'specialty practice' and
'practice busyness'. CONCLUSIONS: These results suggest that the use of clinical
practice guidelines by Japanese dentists may still be inadequate. Training in the
use of the guidelines could be given to dental students as undergraduate
education and to young clinicians as continuing education.
PMID- 27491704
TI - Quantitative assessment of intrinsic noise for visually guided behaviour in
zebrafish.
AB - All sensory devices, whether biological or artificial, carry appreciable amounts
of intrinsic noise. When these internally generated perturbations are
sufficiently large, the behaviour of the system is not solely driven by the
external stimulus but also by its own spontaneous variability. Behavioural
internal noise can be quantified, provided it is expressed in relative units of
the noise source externally applied by the stimulus. In humans performing sensory
tasks at near threshold performance, the size of internal noise is roughly
equivalent to the size of the response fluctuations induced by the external noise
source. It is not known how the human estimate compares with other animals,
because behavioural internal noise has never been measured in other species. We
have adapted the methodology used with humans to the zebrafish, a small teleost
that displays robust visually-guided behaviour. Our measurements demonstrate
that, under some conditions, it is possible to obtain viable estimates of
internal noise in this vertebrate species; the estimates generally fall within
the human range, suggesting that the properties of internal noise may reflect
general constraints on stimulus-response coupling that apply across animal
systems with substantially different characteristics.
PMID- 27491705
TI - Spatial frequency processing in the central and peripheral visual field during
scene viewing.
AB - Visuospatial attention and gaze control depend on the interaction of foveal and
peripheral processing. The foveal and peripheral regions of the visual field are
differentially sensitive to parts of the spatial-frequency spectrum. In two
experiments, we investigated how the selective attenuation of spatial frequencies
in the central or the peripheral visual field affects eye-movement behavior
during real-world scene viewing. Gaze-contingent low-pass or high-pass filters
with varying filter levels (i.e., cutoff frequencies; Experiment 1) or filter
sizes (Experiment 2) were applied. Compared to unfiltered control conditions,
mean fixation durations increased most with central high-pass and peripheral low
pass filtering. Increasing filter size prolonged fixation durations with
peripheral filtering, but not with central filtering. Increasing filter level
prolonged fixation durations with low-pass filtering, but not with high-pass
filtering. These effects indicate that fixation durations are not always longer
under conditions of increased processing difficulty. Saccade amplitudes largely
adapted to processing difficulty: amplitudes increased with central filtering and
decreased with peripheral filtering; the effects strengthened with increasing
filter size and filter level. In addition, we observed a trade-off between
saccade timing and saccadic selection, since saccade amplitudes were modulated
when fixation durations were unaffected by the experimental manipulations. We
conclude that interactions of perception and gaze control are highly sensitive to
experimental manipulations of input images as long as the residual information
can still be accessed for gaze control.
PMID- 27491706
TI - In vitro evaluation of the schistosomicidal effect of the extracts, fractions and
major 3-hydroxy-2,6-dialkyl-substituted piperidine alkaloids from the flowers of
Senna spectabilis (Fabaceae).
AB - In this work, we present the in vitro schistosomicidal activity evaluation of the
most active dichloromethane fraction (FDm) (ED50=83.5MUg/mL) and of a mixture of
the major alkaloids ((-)-cassine/(-)-spectaline, C/E) (ED50=37.4MUg/mL) from the
flowers of Senna spectabilis against adult worms and cercariae. We also
demonstrate other toxic effects including paralysis of the adult worms,
inhibition of the secretory activity, tegument lesions and cercaricidal activity.
In the association test of Praziquantel (PZQ)-C/E, we observed up to 80%
mortality of Schistosoma mansoni in comparison to PZQ monotherapy. Due to the
diversity of the toxic effects, the schistosomicidal activity of C/E is likely a
result of a multitarget mechanism involving the tegument, secretory system and
neuromotor action.
PMID- 27491707
TI - Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in
vitro synergistic anticancer activity as apoptosis inducer.
AB - Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis
induced ability of two series of novel nitric oxide-releasing spirolactone-type
diterpenoid derivatives (10a-f and 15a-f). All the title compounds were more
potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel
7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data.
Compound 15d exhibited the strongest antiproliferative activity with the IC50 of
0.86, 1.74, 1.16 and 3.75MUM, respectively, and could produce high level (above
25MUM) of NO at the time point of 60min. Further mechanism evaluation showed that
15d could induce S phase cell cycle arrest and apoptosis at low micromolar
concentrations in Bel-7402 cells via mitochondria-related pathways. It was
expected that the remarkable biological profile of the synthetic NO-releasing
spirolactone-type diterpenoid analogs make them possible as promising candidates
for the development of anticancer agents.
PMID- 27491708
TI - Discovery of novel potent imidazo[1,2-b]pyridazine PDE10a inhibitors.
AB - Design and optimization of a novel series of imidazo[1,2-b]pyridazine PDE10a
inhibitors are described. Compound 31 displays excellent pharmacokinetic
properties and was also evaluated as an insulin secretagogue in vitro and in
vivo.
PMID- 27491709
TI - Synthesis and biological evaluation of novel imidazol-1-ylacetic acid derivatives
as non-brain penetrant bombesin receptor subtype-3 (BRS-3) agonists.
AB - Novel compounds based on 1a were synthesized with the focus of obtaining agonists
acting upon peripheral BRS-3. To identify potent anti-obesity compounds without
adverse effects on the central nervous system (CNS), a carboxylic acid moiety and
a labile carboxylic ester with an antedrug functionality were introduced. Through
the extensive synthetic exploration and the pharmacokinetic studies of
intravenous administration in mice, the ester 2b was selected owing to its most
suitable pharmacological profile. In the evaluation of food intake suppression in
C57BL/6N mice, 2b showed significant in vivo efficacy and no clear adverse
effects on blood pressure change in dogs administered the compound by intravenous
infusion.
PMID- 27491710
TI - Vialinin A and thelephantin G, potent inhibitors of tumor necrosis factor-alpha
production, inhibit sentrin/SUMO-specific protease 1 enzymatic activity.
AB - Several p-terphenyl compounds have been isolated from the edible Chinese mushroom
Thelephora vialis. Vialinin A, a p-terphenyl compound, strongly inhibits tumor
necrosis factor-alpha production and release. Vialinin A inhibits the enzymatic
activity of ubiquitin-specific peptidase 5, one of the target molecules in RBL
2H3 cells. Here we examined the inhibitory effect of p-terphenyl compounds,
including vialinin A, against sentrin/SUMO-specific protease 1 (SENP1) enzymatic
activity. The half maximal inhibitory concentration values of vialinin A and
thelephantin G against full-length SENP1 were 1.64+/-0.23MUM and 2.48+/-0.02MUM,
respectively. These findings suggest that p-terphenyl compounds are potent SENP1
inhibitors.
PMID- 27491711
TI - Optimization of microtubule affinity regulating kinase (MARK) inhibitors with
improved physical properties.
AB - Inhibition of microtubule affinity regulating kinase (MARK) represents a
potentially attractive means of arresting neurofibrillary tangle pathology in
Alzheimer's disease. This manuscript outlines efforts to optimize a
pyrazolopyrimidine series of MARK inhibitors by focusing on improvements in
potency, physical properties and attributes amenable to CNS penetration. A unique
cylcyclohexyldiamine scaffold was identified that led to remarkable improvements
in potency, opening up opportunities to reduce MW, Pgp efflux and improve
pharmacokinetic properties while also conferring improved solubility.
PMID- 27491712
TI - The flexible feedstock concept in Industrial Biotechnology: Metabolic engineering
of Escherichia coli, Corynebacterium glutamicum, Pseudomonas, Bacillus and yeast
strains for access to alternative carbon sources.
AB - Most biotechnological processes are based on glucose that is either present in
molasses or generated from starch by enzymatic hydrolysis. At the very high,
million-ton scale production volumes, for instance for fermentative production of
the biofuel ethanol or of commodity chemicals such as organic acids and amino
acids, competing uses of carbon sources e.g. in human and animal nutrition have
to be taken into account. Thus, the biotechnological production hosts E. coli, C.
glutamicum, pseudomonads, bacilli and Baker's yeast used in these large scale
processes have been engineered for efficient utilization of alternative carbon
sources. This flexible feedstock concept is central to the use of non-glucose
second and third generation feedstocks in the emerging bioeconomy. The metabolic
engineering efforts to broaden the substrate scope of E. coli, C. glutamicum,
pseudomonads, B. subtilis and yeasts to include non-native carbon sources will be
reviewed. Strategies to enable simultaneous consumption of mixtures of native and
non-native carbon sources present in biomass hydrolysates will be summarized and
a perspective on how to further increase feedstock flexibility for the
realization of biorefinery processes will be given.
PMID- 27491713
TI - Pellagra Secondary to Medication and Alcoholism: A Case Report and Review of the
Literature.
AB - Pellagra usually results from niacin deficiency and presents with the classic
triad of dermatitis, diarrhea, and dementia. It is most commonly associated with
malnutrition and poverty and is extremely rare in industrialized societies.
Furthermore, pellagra can be induced by special clinical conditions that
interfere with the intake, absorption, and metabolism of niacin. Because of its
detrimental effects on health and its favorable prognosis after supplementation
of nicotinamide, the importance of early diagnosis and treatment should be
emphasized. Herein, we report a case of pellagra in a young alcoholic who
underwent combined chemotherapy for tuberculosis. For the first time, a
descriptive review of literature from 1957 to 2014 has been conducted to clarify
potential etiologies of pellagra: alcoholism (35.24%, 37 articles), various
medications (25.71%, 27 articles), inadequate oral intake (16.19%, 17 articles),
malabsorption (13.33%, 14 articles), metabolic derangement (7.62%, 8 articles),
excessive loss (0.95%, 1 article), and etiology unknown (0.95%, 1 article).
PMID- 27491716
TI - Scenario analysis and disaster preparedness for port and maritime logistics risk
management.
AB - System Dynamics (SD) modelling is used to investigate the impacts of policy
interventions on industry actors' preparedness to mitigate risks and to recover
from disruptions along the maritime logistics and supply chain network. The model
suggests a bi-directional relation between regulation and industry actors'
behaviour towards Disaster Preparedness (DP) in maritime logistics networks. The
model also showed that the level of DP is highly contingent on forecast accuracy,
technology change, attitude to risk prevention, port activities, and port
environment.
PMID- 27491714
TI - Transition to a Tube Feeding Formula With Real Food Ingredients in Pediatric
Patients With Intestinal Failure.
AB - Due to concerns related primarily to allergic response and malabsorption, enteral
nutrition therapy has traditionally relied on the use of elemental formulas in
children with intestinal failure (IF). Blended food diets via a gastrostomy tube
have been reported to improve feeding tolerance in pediatric populations
receiving long-term enteral nutrition therapy. Complex macronutrients have been
shown to stimulate intestinal adaptation in animal models. We report on our
experience in children with IF who had an overall improvement in stool output
when transitioned from an elemental formula to a tube feeding formula with real
food ingredients (TFRF). Data were collected in a retrospective chart review of
children with IF, >1 year of age, who were receiving enteral nutrition via
continuous infusion, bolus feeding, or both. Indications for the TFRF trial were
diarrhea or inconsistent stooling patterns. Ten children with a mean small bowel
length of 48.3 cm were trialed on TFRF. Nine of 10 (90%) children tolerated the
transition to 100% TFRF, of which 7 of 9 (78%) had their entire colon in
continuity. The average age at successful transition was 29.2 months, and the
average length of time to transition to 100% TFRF was 67.3 days. TFRF is well
tolerated in children >1 year of age with IF; it also improves their stooling
patterns. A commercially available TFRF is a cost-effective and nutritionally
adequate means of providing nutrition to this patient population.
PMID- 27491717
TI - Incidents between Straight-ahead Cyclists and Right-turning Motor Vehicles at
Signalised Junctions.
AB - Accidents between right-turning motor vehicles and straight-ahead cyclists are
one of the most common accident types leading to cyclist injuries at signalised
junctions in Denmark. A before-after safety evaluation of applying staggered stop
lines in 189 arms at 123 signalised junctions is presented. The evaluation
accounts for long-term accident trends and changes in motor vehicle traffic
volumes. Applying staggered stop lines gives no decline in accidents between
right-turning motor vehicles and straight-ahead cyclists. However, there is a
statistical tendency to a decline of these right-turn accidents involving heavy
vehicles. There are several questions about factors leading to right-turn
accidents that cannot be answered by recorded accident data. A study of
conflicting behaviour focuses on factors leading to conflicts. Video observations
have been carried out in 10 arms at signalised junctions. A total of 45
situations with conflicting behaviour between right-turning motor vehicles and
straight-ahead cyclists have been investigated and compared to a reference group
of simultaneous arrivals. The relative risk is lowest when both parties stop on
red before entering the junction. Upon simultaneous arrival of both parties at a
green light, the relative risk is highest. Cyclists tend to have a higher
relative risk of being involved in conflicts if they; a) ride through on yellow,
b) have a time distance of at least 2seconds to other cyclists, c) wear a black
jacket, and/or d) arrive at the junction at a speed of at least 25km/h. Much less
can be said about the motor vehicles or their drivers on the basis of these video
observations, but motor vehicles stopping in the cycle crossing in order to yield
to pedestrians or cyclists have a higher relative risk of being involved in
conflicts.
PMID- 27491718
TI - Comparison of Thyroglobulin Measurements Using Three Different Immunoassay Kits:
A BRAMHS Tg-Plus RIA Kit, a BRAMHS hTg Sensitive Kryptor Kit, and a Beckman
Coulter ACCESS Immunoassay Kit.
AB - BACKGROUND: Second-generation thyroglobulin immunometric assays (Tg-IMAs) have
been developed with improved sensitivity. Our aim was to compare the diagnostic
value of Tg-IMA measurements using a Kryptor (BRAHMS AG) kit (Tg-K) and an ACCESS
(Beckman Coulter) kit (Tg-A) with that of the first-generation Tg measurement
using a Tg-plus (BRAHMS AG) kit (Tg+). METHODS: We enrolled 82 differentiated
thyroid cancer patients who underwent total thyroidectomy with radioactive iodine
remnant ablation and who underwent diagnostic whole body scan using recombinant
human thyroid stimulating hormone (rhTSH). The Tg+, Tg-K, and Tg-A were measured
before rhTSH administration during levothyroxine treatment (suppressed Tg) from
the same sample. Serum Tg+ was measured after rhTSH stimulation (stimulated Tg).
RESULTS: Suppressed Tg+ was more significantly correlated with suppressed Tg-K
(R2=0.919, P<0.001) than with suppressed Tg-A (R2=0.536, P<0.001). The optimal
cut-off values of suppressed Tg+, Tg-K, and Tg-A for predicting stimulated Tg+ of
1 ng/mL were 0.3, 0.2, and 0.2 ng/mL, respectively. The sensitivity, specificity,
and accuracy of suppressed Tg+ were 67%, 100%, and 90%, respectively; those of
suppressed Tg-K were 83%, 90%, and 88%; those of suppressed Tg-A were 96%, 82%,
and 87%, respectively. The positive predictive and negative predictive values of
Tg+ were 100% and 87%, respectively; those of Tg-K were 79% and 92%; and those of
Tg-A were 73% and 98%. CONCLUSION: We could not clearly demonstrate which kit had
better diagnostic performance after comparison of first-generation Tg
measurements with Tg-IMA measurements. Also, there were kit-to-kit variations
between Tg-IMA kits. Suppressed Tg measured by Tg-IMA was insufficient to
completely substitute for a stimulated Tg measurement.
PMID- 27491719
TI - Prevalence of Reduced Kidney Function by Estimated Glomerular Filtration Rate
Using an Equation Based on Creatinine and Cystatin C in Metabolic Syndrome and
Its Components in Korean Adults.
AB - BACKGROUND: It is known that metabolic syndrome (MetS) is associated with chronic
kidney disease. We evaluated and compared the prevalence of reduced kidney
function in MetS and its components by estimated glomerular filtration rate
(eGFR) using an equation based on creatinine (eGFRcr), cystatin C (eGFRcys), and
combined creatinine-cystatin C (eGFRcr-cys) in Korean adults. METHODS: We
analyzed data from 3,649 adults who participated in a comprehensive health
examination. RESULTS: Mean values of eGFRcys were higher compared with mean
values of eGFRcr (96.1+/-18.2 mL/min/1.73 m2 vs. 91.2+/-13.6 mL/min/1.73 m2) in
total subjects. The prevalence of reduced kidney function increased with age
(9.6% for eGFRcys vs. 5.8% for eGFRcr-cys vs. 4.9% for eGFRcr, in subjects aged
>=60 years), and significantly increased with MetS, abdominal obesity,
hypertension, high triglyceride, low high density lipoprotein (HDL), and high
insulin resistance. The prevalence of MetS, abdominal obesity, hypertension, high
insulin resistance, low HDL, and hepatic steatosis was significantly increased in
subjects with reduced kidney function. This increased prevalence and the odds
ratio of reduced kidney function for prevalence of MetS was highest for eGFRcys,
followed by those of eGFRcr-cys, and eGFRcr. CONCLUSION: The prevalence of
reduced kidney function by eGFR was significantly increased in subjects with MetS
and its related components. eGFRcys and eGFRcr-cys were superior to eGFRcr in
detecting reduced kidney function.
PMID- 27491720
TI - Macrophage Densities Correlated with CXC Chemokine Receptor 4 Expression and
Related with Poor Survival in Anaplastic Thyroid Cancer.
AB - BACKGROUND: Tumor associated macrophages (TAMs) and CXC chemokine receptor 4
(CXCR4) have emerged as potential biomarkers in various human cancers. The aims
of this study were to investigate the clinical characteristics of anaplastic
thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue,
and to evaluate the associations between CXCR4 expressions and macrophage
densities in ATC tumor microenvironment. METHODS: Total 14 ATC samples from
thyroid tissue microarray were used. Immunohistochemical staining was performed
using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of
CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163
(n=6) groups. RESULTS: The mean diagnostic age was 65+/-7 years and the median
tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics
were not significantly different between low-CD163 and high-CD163 groups, while
age of diagnosis was younger in high-CD163 group than that of low-CD163 group
with marginal significance (56.9+/-5.5 years vs. 67.5+/-6.8 years, P=0.09).
However, overall survival was significantly reduced in high-CD163 group (5.5
months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to
121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4
expressions in both cancer and stromal compartments, while low-CD163 group showed
relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and
CXCR4 expressions showed a strong positive correlation (gamma2=0.432, P=0.013).
CONCLUSION: Increased number of TAMs showed poor overall survival in ATC,
suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression
was significantly correlated with CD163-positive TAM densities, which suggest the
possible role of CXCR4 in TAM recruitments.
PMID- 27491721
TI - Time to tackle the incumbency advantage in science: A survey of scientists shows
strong support for funding policies that would distribute funds more evenly among
laboratories and thereby benefit new and smaller research groups.
PMID- 27491722
TI - What is the meaning of Brexit?
PMID- 27491723
TI - The economic costs of mental disorders: Do our societies react appropriately to
the burden of mental disorders?
PMID- 27491724
TI - Management of type 2 diabetes: the current situation and key opportunities to
improve care in the UK.
AB - In common with global trends, the number of individuals with type 2 diabetes in
the UK is rising, driven largely by obesity. The increasing prevalence of younger
individuals with type 2 diabetes is of particular concern because of the
accelerated course of diabetes-related complications that is observed in this
population. The importance of good glycaemic control in the prevention of
microvascular complications of diabetes is widely accepted, and there is a
growing body of evidence to support a benefit in the reduction of cardiovascular
events in the long term. Despite the importance of maintaining a healthy weight
for the prevention of type 2 diabetes, the results from trials of lifestyle
intervention strategies to reduce body weight have been disappointing. New
glucose-lowering agents offer some promise in this regard, offering an
opportunity to combat the dual burden of hyperglycaemia and obesity
simultaneously. The timing and appropriate choice of glucose-lowering therapy has
never been more complex as a result of rising prevalence of obesity in the young,
concomitant obesity in some 90% of adults with type 2 diabetes and an ever
increasing range of therapeutic options. The present review evaluates performance
measures specific to weight and glycaemic control in type 2 diabetes in the UK
using data from the Quality and Outcomes Framework in England and Wales, and the
Scottish Diabetes Survey. Potential barriers to improvement in standards of care
for people with type 2 diabetes are considered, including patient factors,
clinical inertia and the difficulties in translating therapeutic guidelines into
everyday clinical practice.
PMID- 27491725
TI - Synthesis of 2,2'-biphenols through direct C(sp(2))-H hydroxylation of [1,1'
biphenyl]-2-ols.
AB - A novel synthesis of diversely substituted 2,2'-biphenols through Pd(ii)
catalyzed, (t)BuOOH-oxidized, and hydroxyl-directed C(sp(2))-H hydroxylation of
[1,1'-biphenyl]-2-ols has been developed. Notably, this finding is distinct from
previous reports in which [1,1'-biphenyl]-2-ols underwent an intramolecular C-H
activation and C-O bond formation to afford dibenzofurans under the promotion of
Pd(ii) but in the absence of (t)BuOOH.
PMID- 27491727
TI - Charging System Optimization of Triboelectric Nanogenerator for Water Wave Energy
Harvesting and Storage.
AB - Ocean waves are one of the most promising renewable energy sources for large
scope applications due to the abundant water resources on the earth.
Triboelectric nanogenerator (TENG) technology could provide a new strategy for
water wave energy harvesting. In this work, we investigated the charging
characteristics of utilizing a wavy-structured TENG to charge a capacitor under
direct water wave impact and under enclosed ball collision, by combination of
theoretical calculations and experimental studies. The analytical equations of
the charging characteristics were theoretically derived for the two cases, and
they were calculated for various load capacitances, cycle numbers, and structural
parameters such as compression deformation depth and ball size or mass. Under the
direct water wave impact, the stored energy and maximum energy storage efficiency
were found to be controlled by deformation depth, while the stored energy and
maximum efficiency can be optimized by the ball size under the enclosed ball
collision. Finally, the theoretical results were well verified by the
experimental tests. The present work could provide strategies for improving the
charging performance of TENGs toward effective water wave energy harvesting and
storage.
PMID- 27491726
TI - Association of Gestational Hypertensive Disorders with Retinopathy of
prematurity: A Systematic Review and Meta-analysis.
AB - The role of gestational hypertensive disorders, which includes both pre-eclampsia
and gestational hypertension, in the development of retinopathy of prematurity
(ROP) has been controversial. Therefore, this systematic review and meta-analysis
is to evaluate the association between gestational hypertensive disoders and ROP.
Eligible studies published up to June 5, 2016 were identified from MEDLINE and
EMBASE that evaluated the association between the two conditions. Totally 1142
published records were retrieved for screening, 925 of them eligible for detailed
evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met
our criteria for meta-analysis. Gestational hypertensive disorders were not
associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18).
Subgroup analyses also revealed no significant association between ROP with pre
eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR:1.29; P = 0.28) or with
gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P =
0.60) separately. Sensitivity analysis indicated our results were robust. We
concluded no significant association between gestational hypertensive disorders
and ROP. More large scale well-conducted prospective cohorts on the topic are
needed.
PMID- 27491728
TI - Hydrogen bonding asymmetric star-shape derivative of bile acid leads to
supramolecular fibrillar aggregates that wrap into micrometer spheres.
AB - We report that star-shaped molecules with cholic acid cores asymmetrically
grafted by low molecular weight polymers with hydrogen bonding end-groups undergo
aggregation to nanofibers, which subsequently wrap into micrometer spherical
aggregates with low density cores. Therein the facially amphiphilic cholic acid
(CA) is functionalized by four flexible allyl glycidyl ether (AGE) side chains,
which are terminated with hydrogen bonding 2-ureido-4[1H]pyrimidinone (UPy) end
groups as connected by hexyl spacers, denoted as CA(AGE6-C6H12-UPy)4. This wedge
shaped molecule is expected to allow the formation of a rich variety of solvent
dependent structures due to the complex interplay of interactions, enabled by its
polar/nonpolar surface-active structure, the hydrophobicity of the CA in aqueous
medium, and the possibility to control hydrogen bonding between UPy molecules by
solvent selection. In DMSO, the surfactant-like CA(AGE6-C6H12-UPy)4 self
assembles into nanometer scale micelles, as expected due to its nonpolar CA
apexes, solubilized AGE6-C6H12-UPy chains, and suppressed mutual hydrogen bonds
between the UPys. Dialysis in water leads to nanofibers with lateral dimensions
of 20-50 nm. This is explained by promoted aggregation as the hydrogen bonds
between UPy molecules start to become activated, the reduced solvent
dispersibility of the AGE-chains, and the hydrophobicity of CA. Finally, in pure
water the nanofibers wrap into micrometer spheres having low density cores. In
this case, strong complementary hydrogen bonds between UPy molecules of different
molecules can form, thus promoting lateral interactions between the nanofibers,
as allowed by the hydrophobic hexyl spacers. The wrapping is illustrated by
transmission electron microscopy tomographic 3D reconstructions. More generally,
we foresee hierarchically structured matter bridging the length scales from
molecular to micrometer scale by sequentially triggering supramolecular
interactions.
PMID- 27491729
TI - Relationship between the surgical margin status, prognosis, and recurrence in
extrahepatic bile duct cancer patients.
AB - PURPOSE: The purpose of this retrospective study was to evaluate the relationship
between the surgical margin status of the bile duct and the prognosis and
recurrence of extrahepatic bile duct (EHBD) cancer. METHODS: The clinical data of
100 patients who underwent surgery for EHBD cancer between February 2002 and
September 2014 were analyzed. The ductal margin status was classified into the
following three categories: negative (D-N), positive with carcinoma in situ (D
CIS), and positive with invasive carcinoma (D-INV). RESULTS: The number of
patients with D-N, D-CIS, and D-INV was 69, 16, and 15, respectively. Local
recurrence rates of patients with D-CIS (56.3 %) and D-INV (66.7 %) were
significantly higher compared to those of patients with D-N (10.1 %; P < 0.001).
D-CIS was a significant predictor of shorter recurrence-free survival (RFS).
Lymph node metastasis (P = 0.037) and D-INV (P = 0.008) were independent
predictors of shorter disease-specific survival (DSS). The prognostic relevance
of the ductal margin status was high, particularly in patients without lymph node
metastasis. CONCLUSION: The surgical margin status of the bile duct was
significantly associated with RFS, DSS, and the recurrence site.
PMID- 27491730
TI - Organizational Update: European Stroke Organisation.
PMID- 27491731
TI - Good Intracranial Collaterals Trump Poor ASPECTS (Alberta Stroke Program Early CT
Score) for Intravenous Thrombolysis in Anterior Circulation Acute Ischemic
Stroke.
AB - BACKGROUND AND PURPOSE: In acute ischemic stroke, large early infarct size
estimated by the Alberta Stroke Program Early CT Score (ASPECTS) is associated
with poorer outcomes and is a relative contraindication for recanalization
therapies. The state of the intracranial collateral circulation influences the
functional outcome and may be a variable to consider before thrombolysis. We
evaluated the prognostic effect of the collateral circulation in patients with
thrombolyzed acute ischemic stroke who have large early infarct sizes as
indicated by low ASPECTS. MATERIALS AND METHODS: Patients with anterior
circulation acute ischemic stroke who received a computed tomographic angiogram
and subsequent treatment with intravenous tissue-type plasminogen activator from
2010 to 2013 were studied. Two independent neuroradiologists determined their
ASPECTS. We stratified patients using ASPECTS into 2 groups: large volume
infarcts (ASPECTS<=7 points) and small volume infarcts (ASPECTS 8-10). In
addition, we evaluated a third group with very large volume infarcts (ASPECTS<=5
points). We then analyzed the 3 subgroups using the Maas, Tan, and ASPECTS
collaterals grading systems of the computed tomographic angiogram intracranial
collaterals. Good outcomes were defined by modified Rankin Scale score of 0 to 2
at 3 months. RESULTS: A total of 300 patients were included in the final
analysis. For patients with very large volume infarcts (ASPECTS<=5 points),
univariable analysis showed that younger age, male sex, lower National Institute
of Health Stroke Scale (NIHSS), lower systolic blood pressure, and good
collaterals by Maas, Tan, or ASPECTS-collaterals grading were predictors of good
outcomes. On multivariate analysis, younger age (odds ratio, 0.93; 95% confidence
interval, 0.89-0.97; P=0.002) and good collaterals by ASPECTS-collaterals system
(odds ratio, 1.34; 95% confidence interval, 1.15-1.57; P<0.001) were associated
with good outcomes. CONCLUSIONS: In patients with large and very large volume
infarcts, good collaterals as measured by the ASPECTS-collaterals system is
associated with improved outcomes and can help select patients for intravenous
thrombolysis.
PMID- 27491732
TI - Does Increased Arterial Stiffness Herald Cognitive Impairment?
PMID- 27491733
TI - FABS: An Intuitive Tool for Screening of Stroke Mimics in the Emergency
Department.
AB - BACKGROUND AND PURPOSE: A large number of patients with symptoms of acute
cerebral ischemia are stroke mimics (SMs). In this study, we sought to develop a
scoring system (FABS) for screening and stratifying SM from acute cerebral
ischemia and to identify patients who may require magnetic resonance imaging to
confirm or refute a diagnosis of stroke in the emergency setting. METHODS: We
designed a scoring system: FABS (6 variables with 1 point for each variable
present): absence of Facial droop, negative history of Atrial fibrillation, Age
<50 years, systolic Blood pressure <150 mm Hg at presentation, history of
Seizures, and isolated Sensory symptoms without weakness at presentation. We
evaluated consecutive patients with symptoms of acute cerebral ischemia and a
negative head computed tomography for any acute finding within 4.5 hours after
symptom onset in 2 tertiary care stroke centers for validation of FABS. RESULTS:
A total of 784 patients (41% SMs) were evaluated. Receiver operating
characteristic curve (C statistic, 0.95; 95% confidence interval [CI], 0.93-0.98)
indicated that FABS>=3 could identify patients with SM with 90% sensitivity (95%
CI, 86%-93%) and 91% specificity (95% CI, 88%-93%). The negative predictive value
and positive predictive value were 93% (95% CI, 90%-95%) and 87% (95% CI, 83%
91%), respectively. CONCLUSIONS: FABS seems to be reliable in stratifying SM from
acute cerebral ischemia cases among patients in whom the head computed tomography
was negative for any acute findings. It can help clinicians consider advanced
imaging for further diagnosis.
PMID- 27491734
TI - Use and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in
Patients >=90 Years of Age.
AB - BACKGROUND AND PURPOSE: Intravenous tissue-type plasminogen activator (tPA) is a
proven treatment for acute ischemic stroke, but there has been limited evaluation
among patients aged >=90 years. METHODS: We analyzed data from the Get With The
Guidelines-Stroke national quality improvement registry from January 2009 to
April 2013. Frequency, determinants, and outcomes of tPA use were compared among
patients aged >=90 and 3 younger age groups (18-64, 65-79, and 80-89 years).
RESULTS: Among 35 708 patients from 1178 sites who arrived within 2 hours of time
last known well and received tPA, 2585 (7.2%) were >=90 years. Compared with
younger patients, the rate of tPA use among patients without a documented
contraindication was lower among patients aged >=90 years (67.4% versus 84.1% in
18-89-year olds; P<0.0001). Discharge outcomes among individuals aged >=90 years
included discharge to home or acute rehabilitation in 31.4%, independent
ambulation at discharge in 13.4%, symptomatic hemorrhage in 6.1%, and in-hospital
mortality or hospice discharge in 36.4%. On multivariable analysis, good
functional outcomes generally occurred less often and mortality more often among
patients aged >=90 years. The risk of symptomatic hemorrhage was increased
compared with patients <65 years but was not significantly different than the
risk in 66- to 89-year olds. CONCLUSIONS: The use of intravenous tPA among those
aged >=90 years is lower than in younger patients. When fibrinolytic therapy is
used, the risk of symptomatic hemorrhage is not higher than in 66- to 89-year
olds; however, mortality is higher and functional outcomes are lower.
PMID- 27491735
TI - Aortic Stiffness and the Risk of Incident Mild Cognitive Impairment and Dementia.
AB - BACKGROUND AND PURPOSE: Aortic stiffening increases the transfers of high
pressure and flow pulsatility to small cerebral vessels potentially causing the
accumulation of vascular brain injury. Our aim was to investigate the prospective
association of aortic stiffness with the risks of incident mild cognitive
impairment and dementia. METHODS: We studied 1101 dementia-free Framingham
Offspring study participants (mean age, 69+/-6 years; 54% women). Aortic
stiffness was measured as carotid-femoral pulse wave velocity using applanation
tonometry and modeled as a linear variable and the top 2 quintiles (>11.4 m/s).
Outcomes were the 10-year risk of incident mild cognitive impairment and
dementia, including clinically characterized Alzheimer disease. We observed 106,
77, and 59 events of mild cognitive impairment, all-cause dementia, and clinical
Alzheimer disease, respectively. RESULTS: After adjustment for age and sex,
higher continuous aortic stiffness predicted an increased risk of mild cognitive
impairment (hazard ratio, 1.40 [95% confidence interval, 1.13-1.73]), all-cause
dementia (hazard ratio, 1.45 [95% confidence interval, 1.13-1.87]), and Alzheimer
disease (hazard ratio, 1.41 [95% confidence interval, 1.06-1.87]). In risk factor
adjusted statistical models, aortic stiffness remained a significant predictor of
mild cognitive impairment but not incident dementia. In nondiabetic patients, the
top 2 quintiles of aortic stiffness were associated with a higher risk of
incident all-cause dementia across all statistical models. CONCLUSIONS: Aortic
stiffness was an independent predictor of incident mild cognitive impairment in
the whole sample and with incident dementia in nondiabetic patients. Our findings
suggest aortic stiffness as a potentially modifiable risk factor for clinical
cognitive impairment and dementia.
PMID- 27491736
TI - The Capillary Index Score as a Marker of Viable Cerebral Tissue: Proof of Concept
The Capillary Index Score in the MR CLEAN (Multicenter Randomized Clinical Trial
of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Trial.
AB - BACKGROUND AND PURPOSE: The capillary index score (CIS) is based on the
hypothesis that areas lacking capillary blush on pretreatment cerebral digital
subtraction angiograms correspond to nonviable cerebral tissue. METHODS:
Pretreatment digital subtraction angiograms and post-treatment noncontrast
enhanced computed tomographic scans from the MR CLEAN (Multicenter Randomized
Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the
Netherlands) trial were evaluated for areas lacking capillary blush and with
tissue hypodensity, respectively. Because the superior and middle zones of the
CIS correspond to the 7 cerebral cortex regions of the Alberta Stroke Program
Early CT (ASPECT) score, capillary blush was scored in these 2 zones (0-2),
called sub-CIS, and compared with the ASPECT score in these 7 regions (0-7),
called hypodensity score. The presence and extent of hypodensity were compared
between sub-CIS zones with contingency tables and nonparametric comparisons
between groups, respectively. RESULTS: On the basis of a sample size of 50
subjects, 100% with sub-CIS <2 had the presence of hypodensity (hypodensity score
>=1) versus 57% for sub-CIS=2 (P=0.004). The extent of hypodensity (numeric
hypodensity score) was significantly lower for sub-CIS=2 than 0 or 1 (P=0.02).
For 42 subjects with revascularization data, the presence and extent of
hypodensity were significantly lower for sub-CIS=2 plus good revascularization
than for other combinations of sub-CIS and revascularization (P=0.02 and 0.01,
respectively). CONCLUSIONS: The absence of capillary blush on pretreatment
digital subtraction angiogram seems to correspond to nonviable cerebral tissue.
Successful revascularization reduces the chance of tissue hypodensity
(infarction), when capillary blush is present. CLINICAL TRIAL REGISTRATION: URL:
http://www.trialregister.nl. Unique identifier: NTR number 1804. URL:
http://www.isrctn.com. Unique identifier: ISRCTN10888758.
PMID- 27491737
TI - Blood Pressure, Carotid Flow Pulsatility, and the Risk of Stroke: A Community
Based Study.
AB - BACKGROUND AND PURPOSE: High blood pressure is a major cause of cardiovascular
events, and carotid flow pulsatility may be associated with cardiovascular
events. However, the combined effect of blood pressure and flow pulsatility on
the development of stroke remains unclear. Therefore, we investigated the
combined influence of central blood pressure and pulsatility index (PI) on the
incidence of stroke. METHODS: Baseline data from 2033 adults (>=30 years) without
stroke history in the Cardiovascular Disease Risk Factor Two-Township Study were
linked to incident stroke. Common carotid flow PI was calculated by peak systolic
velocity, end-diastolic velocity, and mean vessel velocity, which were measured
in the common carotid artery. Hazard ratios for the risk of total stroke
resulting from high central systolic blood pressure (CSBP) and high PI were
calculated with Cox proportional hazard models. RESULTS: Over a median follow-up
of 9.81 years, 132 people incurred stroke events. The incidence rates of stroke
were 1.3, 6.4, and 13.2 per 1000 person-years for tertile groups of CSBP (P for
trend<0.05) and 4.3, 7.0, and 9.4 per 1000 person-years for tertile groups of PI
(P for trend<0.05). Compared with the first tertile of CSBP, hazard ratios were
4.88 (95% confidence interval, 2.29-10.43) for the second tertile and 10.42 (5.05
21.53) for the third tertile. Hazard ratios of PI were 2.18 (1.39-3.42; third
tertile) and 1.64 (1.02-2.63; second tertile) compared with the first tertile.
The individuals with a high CSBP and high PI had a 13-fold higher stroke risk
compared with those with low CSBP and low PI (13.2; 1.75-99.71) after adjusting
for age, sex, and traditional cardiovascular risk. CONCLUSIONS: CSBP and common
carotid PI jointly and independently predicted future stroke. Carotid flow
pulsatility may play an important role in the development of stroke.
PMID- 27491738
TI - Leukoaraiosis, Cerebral Hemorrhage, and Outcome After Intravenous Thrombolysis
for Acute Ischemic Stroke: A Meta-Analysis (v1).
AB - BACKGROUND AND PURPOSE: We performed a meta-analysis to assess whether
leukoaraiosis on brain computed tomographic scans of acute ischemic stroke
patients treated with intravenous thrombolysis is associated with an increased
risk of symptomatic intracerebral hemorrhage (sICH) or poor functional outcome at
3 to 6 months after stroke, or both. METHODS: We searched PubMed and pooled
relevant data in meta-analyses using random effects models. Using odds ratios
(OR), we quantified the strength of association between the presence and severity
of leukoaraiosis and post-thrombolysis sICH or 3- to 6-month modified Rankin
Score >2. RESULTS: Eleven eligible studies (n=7194) were pooled in meta-analysis.
The risk of sICH was higher in patients with leukoaraiosis (OR, 1.55; 95%
confidence interval [CI], 1.17-2.06; P=0.002) and severe leukoaraiosis (OR, 2.53;
95% CI, 1.92-3.34; P<0.0001) compared with patients without leukoaraiosis.
Leukoaraiosis was an independent predictor of sICH in 6 included studies (n=4976;
adjusted OR, 1.75; 95% CI, 1.35-2.27; P<0.0001). OR for leukoaraiosis and poor 3-
to 6-month outcome was 2.02 (95% CI, 1.54-2.65; P<0.0001), with significant
statistical heterogeneity (I(2), 75.7%; P=0.002). In adjusted analyses,
leukoaraiosis was an independent predictor of poor outcome (n=3688; adjusted OR,
1.61; 95% CI, 1.44-1.79; P<0.0001). In post hoc analyses, including only
leukoaraiosis patients in randomized controlled trials (IST-3 [third
International Stroke Trial], NINDS [National Institute of Neurological Disorders
and Stroke], ECASS-1-2 [European Cooperative Acute Stroke Study]; n=2234), tissue
type plasminogen activator versus control was associated with higher sICH risk
(OR, 5.50; 95% CI, 2.49-12.13), but lower poor outcome risk (OR, 0.75; 95% CI,
0.60-0.95). CONCLUSIONS: Leukoaraiosis might increase post-intravenous
thrombolysis sICH risk and poor outcome poststroke. Despite increased sICH risk,
intravenous tissue-type plasminogen activator treatment has net clinical benefit
in patients with leukoaraiosis. Given the risk of bias/confounding, these results
should be considered hypothesis-generating and do not justify withholding
intravenous thrombolysis.
PMID- 27491739
TI - Protective Effects and Magnetic Resonance Imaging Temperature Mapping of Systemic
and Focal Hypothermia in Cerebral Ischemia.
AB - BACKGROUND AND PURPOSE: Hypothermia is potentially the most effective protective
therapy for brain ischemia; however, its use is limited because of serious side
effects. Although focal hypothermia (FH) has a significantly lower stress profile
than systemic hypothermia (SH), its efficacy in ischemia has been poorly studied.
We aimed to compare the therapeutic effects of each treatment on various short-
and long-term clinically relevant end points. METHODS: Sprague-Dawley rats were
subjected to transient (45 minutes) occlusion of the middle cerebral artery. One
hour after arterial reperfusion, animals were randomly assigned to groups for
treatment with SH or FH (target temperature: 32 degrees C) for 4 or 24 hours.
Lesion volume, edema, functional recovery, and histological markers of cellular
injury were evaluated for 1 month after ischemic injury. Effects of SH and FH on
cerebral temperature were also analyzed for the first time by magnetic resonance
thermometry, an approach that combines spectroscopy with gradient-echo-based
phase mapping. RESULTS: Both therapeutic approaches reduced ischemic lesion
volume (P<0.001), although a longer FH treatment (24 hours) was required to
achieve similar protective effects to those induced by 4 hours of SH. In
addition, magnetic resonance thermometry demonstrated that systemic hypothermia
reduced whole-brain temperature, whereas FH primarily reduced the temperature of
the ischemic region. CONCLUSIONS: Focal brain hypothermia requires longer cooling
periods to achieve the same protective efficacy as SH. However, FH mainly affects
the ischemic region, and therefore represents a promising and nonstressful
alternative to SH.
PMID- 27491740
TI - Determinants in Adolescence of Stroke-Related Hospital Stay Duration in Men: A
National Cohort Study.
AB - BACKGROUND AND PURPOSE: Physical and psychological characteristics in adolescence
are associated with subsequent stroke risk. Our aim is to investigate their
relevance to length of hospital stay and risk of second stroke. METHODS: Swedish
men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using
information from population-based national registers. Stress resilience, body
mass index, cognitive function, physical fitness, and blood pressure were
measured at compulsory military conscription examinations in late adolescence.
Joint Cox proportional hazards models estimated the associations of these
characteristics with long compared with short duration of stroke-related hospital
stay and with second stroke compared with first. RESULTS: Some 3000 men were
diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress
resilience, underweight, and higher systolic blood pressure (per 1-mm Hg
increase) during adolescence were associated with longer hospital stay (compared
with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95%
confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00
1.02), respectively. Elevated systolic and diastolic blood pressures during
adolescence were associated with longer hospital stay in men with intracerebral
hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both
stroke types, obesity in adolescence conferred an increased risk of second
stroke: 2.06 (1.21-3.45). CONCLUSIONS: Some characteristics relevant to length of
stroke-related hospital stay and risk of second stroke are already present in
adolescence. Early lifestyle influences are of importance not only to stroke risk
by middle age but also to recurrence and use of healthcare resources among stroke
survivors.
PMID- 27491742
TI - In-Transit Telemedicine Speeds Ischemic Stroke Treatment: Preliminary Results.
AB - BACKGROUND AND PURPOSE: Time to treatment is critically important in ischemic
stroke. We compared the efficacy and cost of teleneurology evaluation during
patient transport with that of mobile stroke transport units. METHODS: Using
cellular-connected telemedicine devices, we assessed 89 presumptive stroke
patients in ambulances in transit. Paramedics assisted remote teleneurologists in
obtaining a simplified history and examination, then coordinating care with the
receiving emergency department. We prospectively assessed door-to-needle and last
known-well-to-needle times for all intravenous alteplase-treated stroke patients
brought to our emergency departments by emergency medical services' transport,
comparing those with and without in-transit telestroke. RESULTS: From January
2015 through March 2016, 111 stroke patients received intravenous alteplase at
study emergency departments. Mean door to needle was 13 minutes less with in
transit telestroke (28 versus 41; P=0.02). Although limitations in cellular
communication degraded transmission quality, this did not prevent the completion
of satisfactory patient evaluations. CONCLUSIONS: Improvement in time to treat
seems comparable with in-transit telestroke and mobile stroke transport units.
The low cost/unit makes this approach scalable, potentially providing rapid
management of more patients.
PMID- 27491741
TI - Inflammatory Biomarkers in Childhood Arterial Ischemic Stroke: Correlates of
Stroke Cause and Recurrence.
AB - BACKGROUND AND PURPOSE: Among children with arterial ischemic stroke (AIS), those
with arteriopathy have the highest recurrence risk. We hypothesized that
arteriopathy progression is an inflammatory process and that inflammatory
biomarkers would predict recurrent AIS. METHODS: In an international study of
childhood AIS, we selected cases classified into 1 of the 3 most common childhood
AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic
(n=78). We measured serum concentrations of high-sensitivity C-reactive protein,
serum amyloid A, myeloperoxidase, and tumor necrosis factor-alpha. We used linear
regression to compare analyte concentrations across the subtypes and Cox
proportional hazards models to determine predictors of recurrent AIS. RESULTS:
Median age at index stroke was 8.2 years (interquartile range, 3.6-14.3); serum
samples were collected at median 5.5 days post stroke (interquartile range, 3-10
days). In adjusted models (including age, infarct volume, and time to sample
collection) with idiopathic as the reference, the cardioembolic (but not
arteriopathic) group had higher concentrations of high-sensitivity C-reactive
protein and myeloperoxidase, whereas both cardioembolic and arteriopathic groups
had higher serum amyloid A. In the arteriopathic (but not cardioembolic) group,
higher high-sensitivity C-reactive protein and serum amyloid A predicted
recurrent AIS. Children with progressive arteriopathies on follow-up imaging had
higher recurrence rates, and a trend toward higher high-sensitivity C-reactive
protein and serum amyloid A, compared with children with stable or improved
arteriopathies. CONCLUSIONS: Among children with AIS, specific inflammatory
biomarkers correlate with cause and-in the arteriopathy group-risk of stroke
recurrence. Interventions targeting inflammation should be considered for
pediatric secondary stroke prevention trials.
PMID- 27491743
TI - The action and mechanism of myrislignan on A549 cells in vitro and in vivo.
AB - Myrislignan is a natural compound with little pharmacological study. In our
investigation, we investigated the effect of myrislignan in the induction of
apoptosis in A549 cells in vitro and in vivo. Myrislignan inhibited the
proliferation of A549 cells in a dose- and time-dependent manner assayed by MTT.
In addition, Hoechst flow cytometry showed that myrislignan significantly induced
apoptosis and cell cycle arrest in A549 cells. The apoptosis and anti-cell
proliferation was mediated by the activation of mitogen-activated protein kinase
and the inhibition of epidermal growth factor receptor signal pathway, change of
mitochondrial membrane potential, the releasing of c-Myc, the downregulation of
the level of the anti-apoptotic protein Bcl-2, and the upregulation of the level
of the pro-apoptotic protein Bax. In conclusion, those results reveal a potential
mechanism for the anti-cancer effect of myrislignan on human lung cancer, while
suggesting that myrislignan may be a promising compound for the treatment of lung
cancer.
PMID- 27491744
TI - Structure and hemolytic activity relationships of triterpenoid saponins and
sapogenins.
AB - We evaluated the hemolytic activity of 41 commercially available triterpenoid
saponins and sapogenins derived from three types of structural skeletons.
Structure-activity relationships were established by comparing the structural
characteristics of both the aglycone and sugar moieties among the tested
compounds. The majority of oleanane-type sapogenins had stronger hemolytic
effects than those of the ursane and dammarane types. The presence of polar
regions on sapogenins, such as a carboxyl (COOH) at position 28, an alpha
hydroxyl (alpha-OH) at position 16, and/or a beta-hydroxyl (beta-OH) at position
2, significantly enhanced hemolysis. Meanwhile, the introduction of an alpha-OH
at position 2 or a methyl hydroxyl (CH2OH) at positions 23 or 24 was closely
associated with reduced activity. Our findings suggest that not only the
complexity of sugar moieties but also the types and stereochemical configurations
of functional groups at different positions, as well as the skeleton types, are
important structural features affecting hemolytic potential. Our results provide
a baseline in terms of the toxicity of saponins and sapogenins to erythrocytes,
which holds promise for drug development.
PMID- 27491747
TI - Health care and human rights: against the split duty gambit.
AB - There are various grounds on which one may wish to distinguish a right to health
care from a right to health. In this article, I review some old grounds before
introducing some new grounds. But my central task is to argue that separating a
right to health care from a right to health has objectionable consequences. I
offer two main objections. The domestic objection is that separating the two
rights prevents the state from fulfilling its duty to maximise the health it
provides each citizen from its fixed health budget. The international objection
is that separating a human right to health care fails the moral requirement that,
for any given moral human right, the substance to which any two right-holders are
entitled be of an equal standard.
PMID- 27491748
TI - The right to preventive health care.
AB - The right to health care is a right to care that (a) is not too costly to the
provider, considering the benefits it conveys, and (b) is effective in bringing
about the level of health needed for a good human life, not necessarily the best
health possible. These considerations suggest that, where possible, society has
an obligation to provide preventive health care, which is both low cost and
effective, and that health care regulations should promote citizens' engagement
in reasonable preventive health care practices.
PMID- 27491749
TI - Diterpenoids from Callicarpa kwangtungensis and their NO inhibitory effects.
AB - A phytochemical investigation of the leaves of Callicarpa kwangtungensis led to
the isolation of three new diterpenoids (1-3), callipenes A-C, and eleven known
analogues (4-14). Their structures were established on the basis of extensive
analysis of NMR spectroscopic data, X-ray diffraction data, and experimental and
calculated electronic circular dichroism spectra. Compounds 1 and 2 are rare
abietane diterpenoids possessing a peroxide bridge. All of the isolates were
found to inhibit LPS-induced NO production in BV-2 cells.
PMID- 27491750
TI - Chemical structures, production and enzymatic transformations of sapogenins and
saponins from Centella asiatica (L.) Urban.
AB - Centella asiatica (L.) Urban is a medicinal herb traditionally used in Asiatic
countries for its multiple therapeutic properties, essentially due to its
accumulation of specific pentacylic triterpenoid saponins, mainly asiaticoside
and madecassoside and the corresponding sapogenins. This review summarizes the
updated knowledge about the chemical structures of about forty centelloids, found
as minor metabolites in Centella, and all derived from ursane and oleane ring
patterns. Similarly, the most recent genetic and enzymatic features involved in
their biosynthesis is reviewed, in relation with their biotechnological
production developed, either from in vitro plant cultures or undifferentiated
cells, in order to be independent of natural sources and to provide a continuous
and reliable source of centelloids. Finally, a short survey of the
biotransformations of some centelloids, either in animal, human or microorganisms
is reviewed.
PMID- 27491751
TI - Poligalen, a new coumarin from Polygala boliviensis, reduces the release of TNF
and IL-6 independent of NF-kB downregulation.
AB - An unusually substituted coumarin, named poligalen, was isolated from a
chloroform extract of the aerial parts of Polygala boliviensis. This coumarin was
identified by one- and two-dimensional NMR techniques, and the structure of the
compound was confirmed by X-ray diffraction. Poligalen exhibits immunomodulatory
effects, reducing the levels of IL-6 and TNF after LPS stimulation in peritoneal
macrophages. However, poligalen potentiates NF-kB activation.
PMID- 27491752
TI - Tirucallane-type triterpenoids from the fruits of Phellodendron chinense Schneid
and their cytotoxic activities.
AB - Eleven triterpenoids were isolated from the fruits of Phellodendron chinense
Schneid, and their structures were determined by spectroscopic analysis. The
results show that four new tirucallane-type triterpenoids 1, 2, 5, and 6 and
seven known compounds 3, 4, 7, 8, 9, 10, and 11 were isolated. Structurally,
compound 6 was uncommon; it has a chlorine atom instead of a methyl group at the
C-20 position. The cytotoxicities of the compounds was evaluated against the in
vitro proliferation of four human tumor cell lines HEL, K562, MDA, and PC3 using
adriamycin as the positive control. Compound 1 showed a similar cytotoxicity as
the positive control; compounds 3 and 10 showed moderate cytotoxicities compared
to the control (P<0.05). This indicates that these compounds have great potential
for the development of new antitumor drugs.
PMID- 27491753
TI - Sesquiterpenes of agarwood from Gyrinops salicifolia.
AB - Six new sesquiterpenoids (1-6) and six known sesquiterpenoids (7-12) were
isolated from agarwood originated from Gyrinops salicifolia Ridl. Most of them
gave off aromatic odor, and all the compounds were isolated from this genus for
the first time. The structures of 1-6 were elucidated by spectroscopic techniques
(UV, IR, 1D and 2D NMR) and MS analysis, as well as by comparison with literature
data. Compounds 1, 6 and 11-12 showed moderate acetylcholinesterase (AChE)
inhibitory activity.
PMID- 27491754
TI - New sesquiterpene lactones from Ambrosia cumanensis Kunth.
AB - Eleven sesquiterpene lactones, including three new natural products (1-3), were
isolated from the n-butanolic extract of Ambrosia cumanensis Kunth. aerial parts.
The structure of all isolated compounds was elucidated by 1D- and 2D-NMR, and MS
analyses. All compounds were tested for their antiproliferative activity on HeLa,
Jurkat, and U937 cell lines. Compound 3, 2,3-dehydropsilostachyn C, showed
cytotoxic activity with different potency in all cell lines. By means of flow
cytometric studies, compound 3 was demonstrated to induce in Jurkat cells a G2/M
cell cycle block, while in U937 elicited both cytostatic and cytotoxic responses.
PMID- 27491755
TI - Characterization of diterpenoids from Caesalpinia decapetala and their anti-TMV
activities.
AB - Caesalpinia decapetala is a versatile medicinal plant belonging to the Fabaceae
plant family. In our survey on plant secondary metabolites to obtain bioactive
substances for the development of new agricultural anti-TMV agents, the chemical
constituents of C. decapetala were investigated. This investigation led to the
isolation of three new and ten known diterpenoids. Their structures including
absolute configurations were elucidated based on the extensive NMR spectroscopic
data analyses and the time-dependent density functional theory calculations. The
following biological screenings revealed that most of these diterpenoids
possessed anti-TMV activities.
PMID- 27491756
TI - Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent
the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.
AB - A new norlabdane compound, named kujigamberol has previously been isolated from
Kuji amber (but not from Baltic amber) by activity guided fractionation. However,
there has been no study of biological compounds in Dominican amber. Biological
activities were examined using the hypersensitive mutant yeast (zds1Delta
erg3Delta pdr1Delta pdr3Delta) with respect to Ca(2+)-signal transduction,
enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were
elucidated on the basis of spectral analysis including high resolution (HR)-EI
MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid
(1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different
from the bioactive compounds in Kuji and Baltic ambers, were isolated from
Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and
34.2MUM) and glycogen synthase kinase-3beta (GSK-3beta) (IC50=48.9, 43.8 and
41.1MUM) which are involved in the growth restored activity against the mutant
yeast. The most abundant compound 2 showed inhibitory activity against both
degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth
restoring activity against the mutant yeast have potential as anti-allergic
compounds.
PMID- 27491757
TI - Domain motions and electron transfer dynamics in 2Fe-superoxide reductase.
AB - Superoxide reductases are non-heme iron enzymes that represent valuable model
systems for the reductive detoxification of reactive oxygen species. In the
present study, we applied different theoretical methods to study the structural
dynamics of a prototypical 2Fe-superoxide reductase and its influence on electron
transfer towards the active site. Using normal mode and essential dynamics
analyses, we could show that enzymes of this type are capable of well-defined,
electrostatically triggered domain movements, which may allow conformational
proofreading for cellular redox partners involved in intermolecular electron
transfer. Moreover, these global modes of motion were found to enable access to
molecular configurations with decreased tunnelling distances between the active
site and the enzyme's second iron centre. Using all-atom classical molecular
dynamics simulations and the tunnelling pathway model, however, we found that
electron transfer between the two metal sites is not accelerated under these
conditions. This unexpected finding suggests that the unperturbed enzymatic
structure is optimized for intramolecular electron transfer, which provides an
indirect indication of the biological relevance of such a mechanism.
Consistently, efficient electron transfer was found to depend on a distinct
route, which is accessible via the equilibrium geometry and characterized by a
quasi conserved tyrosine that could enable multistep-tunnelling (hopping).
Besides these explicit findings, the present study demonstrates the importance of
considering both global and local protein dynamics, and a generalized approach
for the functional analysis of these aspects is provided.
PMID- 27491758
TI - Generalizing Treatment Effect Estimates From Sample to Population: A Case Study
in the Difficulties of Finding Sufficient Data.
AB - BACKGROUND: Given increasing concerns about the relevance of research to policy
and practice, there is growing interest in assessing and enhancing the external
validity of randomized trials: determining how useful a given randomized trial is
for informing a policy question for a specific target population. OBJECTIVES:
This article highlights recent advances in assessing and enhancing external
validity, with a focus on the data needed to make ex post statistical adjustments
to enhance the applicability of experimental findings to populations potentially
different from their study sample. RESEARCH DESIGN: We use a case study to
illustrate how to generalize treatment effect estimates from a randomized trial
sample to a target population, in particular comparing the sample of children in
a randomized trial of a supplemental program for Head Start centers (the Research
Based, Developmentally Informed study) to the national population of children
eligible for Head Start, as represented in the Head Start Impact Study. RESULTS:
For this case study, common data elements between the trial sample and population
were limited, making reliable generalization from the trial sample to the
population challenging. CONCLUSIONS: To answer important questions about external
validity, more publicly available data are needed. In addition, future studies
should make an effort to collect measures similar to those in other data sets.
Measure comparability between population data sets and randomized trials that use
samples of convenience will greatly enhance the range of research and policy
relevant questions that can be answered.
PMID- 27491759
TI - Soil contamination with olive mill wastes negatively affects microbial
communities, invertebrates and plants.
AB - The aim of the present study was to evaluate the ecotoxicological effects of
olive mill waste (OMW) on soil habitat function. To this end, soil samples from
OMW evaporating ponds (S1-S5) located at Agareb (Sfax, Tunisia) and a reference
soil (R) were collected. The effects of OMW on the springtails Folsomia candida
(F.c.), the earthworm species Eisenia fetida (E.f.), Enchytraeus crypticus (E.c.)
reproduction and on the soil living microbial communities were investigated. E.f.
reproduction and tomato growth assays were performed in the reference soil
amended with 0.43 to 7.60 % (wOMW/wref-soil) mass ratios of dried OMW. Changes in
microbial function diversity were explored using sole-carbon-source utilization
profiles (BiologEcoPlates(r)). E.f. absolutely avoided (100 %) the most polluted
soil (S4) while the F.c. moderately avoided (37.5 +/- 7.5 %) the same soil. E.c.
reproduction in S4 was significantly lower than in S1, S2, S3 and S5, and was the
highest in R soil. Estimated effect concentration EC50 for juveniles' production
by E.f., and for tomato fresh weight and chlorophyll content were 0.138, 0.6 and
1.13 %, respectively. Community level physiological profiles (CLPPs) were
remarkably different in R and S4 and a higher similarity was observed between
soils S1, S2, S3 and S5. Principal component analysis (PCA) revealed that
differences between soil microbial functional diversity were mainly due to high
polyphenol concentrations, while the salinity negatively affected E.c.
reproduction in OMW contaminated soils. These results clearly reflect the high
toxicity of dried OMW when added to agricultural soils, causing severe threats to
terrestrial ecosystem functions and services provided by invertebrates and
microbial communities.
PMID- 27491760
TI - Effect of ultrasound training of physicians working in the prehospital setting.
AB - BACKGROUND: Advances in technology have made ultrasound (US) devices smaller and
portable, hence accessible for prehospital care providers. This study aims to
evaluate the effect of a four-hour, hands-on US training course for physicians
working in the prehospital setting. The primary outcome measure was US
performance assessed by the total score in a modified version of the Objective
Structured Assessment of Ultrasound Skills scale (mOSAUS). METHODS: Prehospital
physicians participated in a four-hour US course consisting of both hands-on
training and e-learning including a pre- and a post-learning test. Prior to the
hands-on training a pre-training test was applied comprising of five videos in
which the participants should identify pathology and a five-minute US examination
of a healthy volunteer portraying to be a shocked patient after a blunt torso
trauma. Following the pre-training test, the participants received a four-hour,
hands-on US training course which was concluded with a post-training test. The US
examinations and screen output from the US equipment were recorded for subsequent
assessment. Two blinded raters assessed the videos using the mOSAUS. RESULTS:
Forty participants completed the study. A significant improvement was identified
in e-learning performance and US performance, (37.5 (SD: 10.0)) vs. (51.3 (SD:
5.9) p = < 0.0001), total US performance score (15.3 (IQR: 12.0-17.5) vs. 17.5
(IQR: 14.5-21.0), p = < 0.0001) and in each of the five assessment elements of
the mOSAUS. CONCLUSION: In the prehospital physicians assessed, we found
significant improvements in the ability to perform US examinations after
completing a four-hour, hands-on US training course.
PMID- 27491761
TI - Bacterial corneal ulcer associated with common variable immune deficiency.
AB - Common variable immune deficiency (CVID) is one of the most commonly diagnosed
primary immunodeficiencies. Generally, patients have a history of recurrent
sinopulmonary infections, hypogammaglobulinemia of two or more immunoglobulin
isotypes, and impaired functional antibody responses. Reports of corneal
involvement associated with CVID are limited. We describe a case of corneal
ulceration associated with methicillin-resistant Staphylococcus aureus in a
patient with CVID that developed while on monthly intravenous immunoglobulin
infusions and in which there were no common risk factors for bacterial keratitis,
such as prior history of ocular surface disease, trichiasis, trauma, or contact
lens wear.
PMID- 27491763
TI - [Not Available].
PMID- 27491762
TI - [Not Available].
PMID- 27491764
TI - [Not Available].
PMID- 27491765
TI - [Not Available].
PMID- 27491766
TI - [Alcohol consumption in women and the elderly : When does it induce heart
failure?].
AB - The association between alcohol consumption and the etiology and prognosis of
cardiovascular diseases has been the focus of attention and also the subject of
controversial discussions for many years. This is particularly true for heart
failure, which can be induced by coronary artery disease (CAD), arterial
hypertension, atrial and ventricular arrhythmias and cardiomyopathies. Acute
effects of high doses of alcohol can lead to impairment of the cardiac
contraction strength with rhythm disturbances (holiday heart syndrome), transient
ischemic attacks and in rare cases to sudden cardiac death. The chronic effects
of high alcohol consumption include in particular, ventricular dysfunction,
chronic rhythm disturbances, alcoholic cardiomyopathy and CAD. In contrast, light
to moderate consumption of alcohol is associated with a reduced risk of CAD and
ischemic stroke; however, even moderate alcohol drinking is associated with a
greater risk for atrial fibrillation. The unfavorable effects of alcohol occur at
much lower levels of acute or chronic consumption in women than in men. In the
elderly just as in young people, a moderate alcohol consumption is associated
with a lower risk of heart failure.
PMID- 27491767
TI - Temporal trends in transcatheter and surgical aortic valve replacement : An
analysis of aortic valve replacements in Germany during 2012-2014.
AB - This analysis of the data of the obligatory quality assurance programme AQUA
shows the perioperative risk as well as the procedural outcome evaluated by the
observed versus expected in-hospital mortality ratio (O/E ratio) of 62,872
patients undergoing isolated surgical (sAVR), transcatheter transvascular (TV-),
or transapical (TA-) aortic valve replacement (TAVI) from 2012 to 2014 in
Germany. The number of TAVI procedures increased from 9,352 in 2012 to 13,278 in
2014, whereas the number of sAVR remained constant (2012: 9,949; 2014: 9,953).
Between 2012 and 2014, the number of TAVI implanted in patients with a logistic
EuroScore I (logESI) of <=10 % (2012: 21 %; 2014: 26 %) as well as with a logESI
<20 % (2012: 57 %; 2014: 64 %) increased. In-hospital mortality in TAVI patients
decreased from 5.2 % (TV: 5.0 %; TA: 7.4 %) in 2012 to 4.2 % (TV: 3.8 %; TA: 5.5
%) in 2014, whereas it was stable for sAVR patients (2012: 2.8 %; 2014: 2.6 %).
The O/E ratio of TAVI patients decreased from 0.91 (TV: 0.79; TA: 1.2) to 0.73
(TV: 0.69; TA: 0.89), whereas this ratio remained constant for sAVR patients
(2012: 0.92; 2014: 0.93). In summary, estimated surgical risk, in-hospital
mortality, as well as the O/E ratio for patients undergoing TAVI declined
constantly during the last 3 years.
PMID- 27491768
TI - Echocardiography in Pregnancy: Part 1.
AB - Cardiovascular disease (CVD) remains the leading cause of maternal mortality, and
clinical diagnosis of CVD in women during pregnancy is challenging. Pregnant
women with known heart disease require careful multidisciplinary management by
obstetric and medical teams to assess for maternal and fetal risk.
Echocardiography is a safe and effective diagnostic tool indicated in pregnant
women with cardiac symptoms or women with known cardiac disease for appropriate
selection of women who require close monitoring of cardiac condition and valvular
function. Echocardiography is the single most important clinical tool to diagnose
and manage heart disease during pregnancy. Echocardiography is able to
characterize cardiac structural abnormalities and corresponding hemodynamic
changes, identifies heart diseases that are poorly tolerated in pregnancy, and
helps select patients who may require a cesarean delivery because of hemodynamic
instability. An understanding of the physiologic alterations including increased
heart rate, blood volume, and cardiac output as well as the decreased vascular
resistance is important for early recognition and monitoring of the consequences
of cardiac disease in pregnancy. This review will focus on common acquired
cardiac lesions encountered during pregnancy and the role of echocardiography in
the diagnosis and management of these diseases.
PMID- 27491769
TI - Depressive symptoms and functional decline following coronary interventions in
older patients with coronary artery disease: a prospective cohort study.
AB - BACKGROUND: Depressive symptoms are prevalent in patients with coronary artery
disease (CAD). It is unclear, however, how depressive symptoms change over time
and the impact of these changes on long-term functional outcomes. We examined the
association between different trajectories of depressive symptoms over 1 year and
change in functional status over 30 months among patients undergoing coronary
angiography. METHODS: This was a prospective cohort study of 350 patients aged 60
and older undergoing non-emergent cardiac catheterization (October 2003-February
2007). A dynamic measure of significant depressive symptoms (i.e., Geriatric
Depression Scale score 5+) capturing change over 12 months was derived that
categorized patients into the following groups: (i) no clinically important
depressive symptoms (at baseline, 6 and 12 months); (ii) baseline-only symptoms
(at baseline but not at 6 and 12 months); (iii) new onset symptoms (not at
baseline but present at either 6 or 12 months); and, (iv) persistent symptoms (at
baseline and at either 6 or 12 month assessment). Primary outcomes were mean
change in Older Americans Resources and Services (OARS) instrumental (IADL) and
basic activities of daily living (BADL) scores (range 0-14 for each) across
baseline (pre-procedure) and 6, 12, and 30 months post-procedure visits. RESULTS:
Estimates for the symptom categories were 71 % (none), 9 % (baseline only), 8 %
(new onset) and 12 % (persistent). In adjusted models, patients with persistent
symptoms showed a significant decrease in mean IADL and BADL scores from baseline
to 6 months (-1.32 [95 % CI -1.78 to -0.86] and -0.63 [-0.97 to -0.30],
respectively) and from 12 to 30 months (-0.79 [-1.27 to -0.31] and -1.00 [-1.35
to -0.65], respectively). New onset symptoms were associated with a significant
decrease in mean IADL scores at 6 months and from 6 to 12 months. Patients with
no depressive symptoms showed little change in scores whereas those with baseline
only symptoms showed significant improvement in mean IADL at 6 months.
CONCLUSIONS: Patients with persistent depressive symptoms were at greatest risk
for worse functional status 30 months following coronary interventions. Proactive
screening and follow-up for depression in this population offers prognostic value
and may facilitate the implementation of targeted interventions.
PMID- 27491770
TI - Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the
promising prognostic markers of oocyte and embryo quality in women with
endometriosis.
AB - PURPOSE: The study aimed to investigate key intrafollicular prognostic factors
among various cytokines and angiogenic molecules for prediction of mature oocytes
and good-quality embryos in women with endometriosis undergoing in vitro
fertilization (IVF). METHODS: Paired follicular fluid and serum samples were
collected from 200 women with advanced stage endometriosis and 140 normal
ovulating women during oocyte retrieval. The concentrations of cytokines (pro
inflammatory: IL-1beta, TNF-alpha, IL-2, IL-8, IL-12, IFN-gamma; anti
inflammatory: IL-4, IL-6, IL-10) and angiogenic molecules (vascular endothelial
growth factor (VEGF), adrenomedullin, angiogenin) were determined in follicular
fluid and serum using ELISA. Expression of these molecules was subjected to
multivariate analysis for the identification of major predictive markers of
oocyte and embryo quality. Receiver operating characteristic (ROC) curve was
applied to determine the best cutoff point for the discrimination between mature
and immature oocytes in these women. RESULTS: Significant increases in levels of
cytokines and angiogenic molecules were observed in women with endometriosis
compared to controls (P < 0.001). From the validated partial least squares
discriminant analysis (PLS-DA) model, IL-8, IL-12, and adrenomedullin were
identified as the most important factors contributing to endometriosis and were
negatively associated with oocyte maturity and embryo quality. CONCLUSION: The
levels of IL-8, IL-12, and adrenomedullin may be good indicators of embryo and
oocyte quality in endometriosis patients undergoing IVF. Further studies are
necessary to ascertain the potential of these markers for oocyte and embryo
developmental competence which may help improve the chances of a successful IVF
in endometriosis patients.
PMID- 27491771
TI - Pre-implantation genetic testing in ART: who will benefit and what is the
evidence?
AB - Pre-implantation genetic diagnosis for aneuploidy testing (PGD-A) is a tool to
identify euploid embryos during IVF. The suggested populations of patients that
can benefit from it are infertile women of advanced maternal age, with a history
of recurrent miscarriages and/or IVF failures. However, a general consensus has
not yet been reached.After the clinical failure of its first version based on
cleavage stage biopsy and 9 chromosome-FISH analysis, PGD-A is currently
performed by 24 chromosome screening techniques on trophectoderm (TE) biopsies.
This approach has been clearly demonstrated to involve a higher clinical
efficiency with respect to the standard care, in terms of sustained pregnancy
rate per transfer and lower miscarriage rate. However, data about PGD-A efficacy
calculated on a per intention-to-treat basis, as well as an analysis of its cost
effectiveness, are still missing.TE biopsy is a safe and extensively validated
approach with low biological and technical margin of error. Firstly, the
prevalence of mosaic diploid/aneuploid blastocysts is estimated to be between 0
and 16 %, thus largely tolerable. Secondly, all the comprehensive chromosome
screening (CCS) technologies adapted to, or designed to conduct PGD-A are highly
concordant, and qPCR in particular has been proven to show the lowest false
positive error rate (0.5 %) and a clinically recognizable error rate per
blastocyst of just 0.21 %.In conclusion, there is a sufficient body of evidence
to support the clinical application of CCS-based PGD-A on TE biopsies. The main
limiting factor is the need for a high-standard laboratory to conduct blastocyst
culture, biopsy and vitrification without impacting embryo viability.
PMID- 27491773
TI - Parental migration and smoking behavior of left-behind children: evidence from a
survey in rural Anhui, China.
AB - BACKGROUND: Parental migration is most an important factor affecting children's
behaviors. Few studies have addressed the association between parental migration
and children's smoking behavior in China. This study aims to estimate the current
smoking prevalence among children, evaluate the association of parental migration
and the smoking behavior of children and identify factors associated with smoking
behavior among left-behind children (LBC). METHODS: A cross-sectional study was
conducted in 6 cities in Anhui province during July and August, 2012. All
participants were interviewed face-to-face using a standardized questionnaire.
Only children 10 to 14 years old that live in rural villages for at least 6
months during the previous year were included in the study. RESULTS: A total of
1343 children met the sampling criteria and participated in the study. Of these,
56 % are LBC and 44 % live with both parents. The average rate of smoking is 3.4
%. The rate of smoking is statistically higher for LBC with both parents out
(rate = 6.1 %; OR = 5.59, P < 0.001) than for children living with both parents
(1.4 %). Similarly, the rate of LBC with father home only (rate = 5.0 %; OR =
5.60, P = 0.005) is also statistically higher than for children living with both
parents when controlling other variables. Factors affecting the smoking behavior
of LBC, include gender (i.e., boys), (perceived) school performance and primary
caregiver. CONCLUSIONS: Parental migration is associated with a significant
increase in smoking behavior among children. Intervention studies that target LBC
would help to develop strategies to reduce smoking among rural children. Gender
specific strategies and anti-smoking education also appears to be needed to
reduce tobacco use among rural LBC.
PMID- 27491772
TI - Blastocyst culture using single versus sequential media in clinical IVF: a
systematic review and meta-analysis of randomized controlled trials.
AB - PURPOSE: The purpose of this study was to undertake a review of the available
evidence comparing the use of a single medium versus sequential media for embryo
culture to the blastocyst stage in clinical IVF. METHODS: We searched the
Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials
and WHO International Clinical Trials Registry Platform to identify randomized
controlled trials comparing single versus sequential media for blastocyst culture
and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or
women. Eligible oocyte/zygote studies were analyzed to assess the risk difference
(RD) and 95 % confidence intervals (CI) between the two media systems; eligible
woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for
clinical pregnancy rate. RESULTS: No differences were observed between single and
sequential media for either ongoing pregnancy per randomized woman (relative risk
(RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2 = 0 %) or
clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one
study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 %
CI = 0.4 to 4.3, two studies including 246 participants, I 2 = 0 %). Single media
use was associated with an increase blastocyst formation per randomized
oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten
studies including 7455 oocytes/zygotes, I 2 = 83 %) but not top/high blastocyst
formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879
oocytes/zygotes, I 2 = 93 %). The overall quality of the evidence was very low
for all these four outcomes. CONCLUSIONS: Although using a single medium for
extended culture has some practical advantages and blastocyst formation rates
appear to be higher, there is insufficient evidence to recommend either
sequential or single-step media as being superior for the culture of embryos to
days 5/6. Future studies comparing these two media systems in well-designed
trials should be performed.
PMID- 27491774
TI - Prediction of drug interaction between oral adsorbent AST-120 and concomitant
drugs based on the in vitro dissolution and in vivo absorption behavior of the
drugs.
AB - PURPOSE: AST-120 is used to decrease the abundance of serum uremic toxins in
treatment of chronic kidney disease; however, it could also adsorb concomitantly
administered drugs. This study aimed to develop a prediction method for drug
interaction between AST-120 and concomitantly administered drugs based on in
vitro dissolution and in vivo absorption behavior. METHODS: Sixty-eight drugs
were selected for the analysis. For each drug, theoretical dissolution (R d) and
absorption (R a) rates at estimated dosing intervals (1, 30, 60, 90, 120, and 240
min) were calculated using the Noyes-Whitney formula and compartment analysis,
respectively. The optimal thresholds for R d and R a (R dth and R ath) were
estimated by comparing the results with those of previous drug interaction
studies for six drugs. Four drug interaction risk categories for 68 drugs at each
dose interval were defined according to the indices of dissolution and absorption
against their thresholds. RESULTS: The in vitro dissolution and in vivo
absorption behavior of the selected drugs were well fitted to the Noyes-Whitney
formula and one- or two-compartment models. The optimal R dth and R ath that gave
the highest value of consistency with the equivalence of drug interaction studies
were 90 and 30 %, respectively. As the dosing intervals were lengthened, the
number of drugs classified into the low-risk categories increased. CONCLUSION: A
new drug interaction prediction method based on the pharmacokinetic parameters of
drugs was developed. The new model is useful for estimating the risk of drug
interaction in clinical practice when AST-120 is used in combination with other
drugs.
PMID- 27491775
TI - Clinical relevance of the utilization of vital Lugol's iodine staining in
detection and diagnosis of oral cancer and dysplasia.
AB - OBJECTIVES: The aim of this study is to assess the clinical relevance of the
utilization of vital Lugol's iodine staining in detection of oral cancer and
dysplastic lesions as well as demarcation of the extent of these lesions.
MATERIALS AND METHODS: A prospective, cross-sectional, hospital-based study was
performed in Khartoum Teaching Dental Hospital, Sudan. Suspicious oral epithelial
lesions indicating incisional biopsy were stained with 10 % Lugol's iodine
solution and were clinically designated as "negative" for dysplasia or neoplasia
when no unstained lesion (USL) area was observed, or as "positive" when a USL
area is observed. Incisional biopsies involving both the unstained portion and
the stained portion were obtained and histologically evaluated for definitive
diagnosis. RESULTS: Forty-five biopsies were obtained from 28 patients.
Histopathological examination of the specimens confirmed some degree of dysplasia
or neoplasia in all clinically positive specimens with oral squamous cell
carcinoma (OSCC) being the most common definitive diagnosis (17 patients, 60.7
%). Clinical relevance level of vital Lugol's iodine staining in detecting oral
cancer and dysplasia was found to be 90.9 % (SE = 0.05, P = 0.05). CONCLUSION:
The findings of this study showed that Lugol's iodine is an easy, safe, and
effective method of visualizing oral epithelial lesions and differentiating
epithelial carcinoma and dysplasia from other benign mucosal lesions. Despite
certain limitations, its use is of great value in detection and diagnosis of oral
cancer and dysplasia. CLINICAL RELEVANCE: Lugol's iodine staining can effectively
be used in detection of the dysplastic and malignant superficial lesions of the
oral epithelium.
PMID- 27491776
TI - The impact of health insurance programs for children: evidence from Vietnam.
AB - This study assesses the impact of children's health insurance programs on health
care utilization and health care expenditures of children from 6 to 14 years old
in Vietnam using four rounds of the Vietnam Household Living Standard Surveys
from 2006 to 2012. We find a positive effect of both student and free health
insurance programs on the number of health care visits. This positive impact
tends to increase over time, and the impact of the free health insurance program
is larger than the impact of the student health insurance program. Regarding out
of-pocket health expenditures per visit, we find a reducing effect on this
outcome of the free health insurance program but not the student health insurance
program.
PMID- 27491777
TI - Decatropis bicolor (Zucc.) Radlk essential oil induces apoptosis of the MDA-MB
231 breast cancer cell line.
AB - BACKGROUND: Decatropis bicolor (Zucc.)Radlk is a plant that has been
traditionally used for the treatment of breast cancer in some communities of
Mexico. So, the aim of this study was to determine the cytotoxic and apoptotic
effect of the essential oil of Decatropis bicolor against breast cancer cell
line, MDA-MB-231. METHODS: The essential oil obtained from hydrodestillation of
leaves of Decatropis bicolor was studied for its biological activity against
breast cancer cells MDA-MB-231 by MTT assay, Hematoxylin-eosin stain, Annexin V
FITC, TUNEL and western blot assays and for its chemical composition by GC-MS.
RESULTS: The results showed a relevant cytotoxic effect of the essential oil
towards MDA-MB-231 cells in a dose- and time- dependent manner, with an IC50 of
53.81 +/- 1.691 MUg/ml but not in the epithelial mammary cell line MCF10A (207.51
+/- 3.26 MUg/ml). Morphological examination displayed apoptotic characteristics
in the treated cells like cell size reduction, membrane blebbing and apoptotic
bodies. In addition, the apoptotic rate significantly increased as well as DNA
fragmentation and western blot analysis revealed that the essential oil induced
apoptosis in the MDA-MB-231 cells via intrinsic pathways due to the activation of
Bax, caspases 9 and 3. Phytochemical analysis of the Decatropis bicolor essential
oil showed the presence of twenty-three compounds. Major components of the oil
were 1,5-cyclooctadiene,3-(methyl-2)propenyl (18.38 %), beta-terpineol (8.16 %)
and 1-(3-methyl-cyclopent-2-enyl)-cyclohexene (6.12 %). CONCLUSIONS: This study
suggests that essential oil of Decatropis bicolor has a potential cytotoxic and
antitumoral effect against breast cancer cells, with the presence of potential
bioactive compounds. Our results contribute to the validation of the anticancer
activity of the plant in Mexican traditional medicine.
PMID- 27491778
TI - Beneficial effects of dark chocolate on exercise capacity in sedentary subjects:
underlying mechanisms. A double blind, randomized, placebo controlled trial.
AB - In heart failure patients the consumption of (-)-epicatechin ((-)-Epi)-rich cocoa
can restore skeletal muscle (SkM) mitochondrial structure and decrease biomarkers
of oxidative stress. However, nothing is known about its effects on exercise
capacity and underlying mechanisms in normal, sedentary subjects. Twenty normal,
sedentary subjects (~50 years old) were randomized to placebo or dark chocolate
(DC) groups and consumed 20 g of the products for 3 months. Subjects underwent
before and after treatment, bicycle ergometry to assess VO2 max and work, SkM
biopsy to assess changes in mitochondrial density, function and oxidative stress
and blood sampling to assess metabolic endpoints. Seventeen subjects completed
the trial. In the DC group (n = 9), VO2 max increased (17% increase, p = 0.056)
as well as maximum work (watts) achieved (p = 0.026) with no changes with placebo
(n = 8). The DC group evidenced increases in HDL levels (p = 0.005) and decreased
triglycerides (p = 0.07). With DC, SkM evidenced significant increases in protein
levels for LKB1, AMPK and PGC1alpha and in their active forms (phosphorylated
AMPK and LKB1) as well as in citrate synthase activity while no changes were
observed in mitochondrial density. With DC, significant increases in SkM reduced
glutathione levels and decreases in protein carbonylation were observed.
Improvements in maximum work achieved and VO2 max may be due to DC activation of
upstream control systems and enhancement of SkM mitochondria efficiency. Larger
clinical studies are warranted to confirm these observations.
PMID- 27491779
TI - Ten-year change in sedentary behaviour, moderate-to-vigorous physical activity,
cardiorespiratory fitness and cardiometabolic risk: independent associations and
mediation analysis.
AB - BACKGROUND: We aimed to study the independent associations of 10-year change in
sedentary behaviour (SB), moderate-to-vigorous physical activity (MVPA) and
objectively measured cardiorespiratory fitness (CRF), with concurrent change in
clustered cardiometabolic risk and its individual components (waist
circumference, fasting glucose, high-density lipoprotein (HDL) cholesterol,
triglycerides and blood pressure). We also determined whether associations were
mediated by change in CRF (for SB and MVPA), waist circumference (for SB, MVPA
and CRF) and dietary intake (for SB). METHODS: A population-based sample of 425
adults (age (mean+/-SD) 55.83+/-9.40; 65% men) was followed prospectively for
9.62+/-0.52 years. Participants self-reported SB and MVPA and performed a maximal
cycle ergometer test to estimate peak oxygen uptake at baseline (2002-2004) and
follow-up (2012-2014). Multiple linear regression and the product of coefficients
method were used to examine independent associations and mediation effects,
respectively. RESULTS: Greater increase in SB was associated with more
detrimental change in clustered cardiometabolic risk, waist circumference, HDL
cholesterol and triglycerides, independently of change in MVPA. Greater decrease
in MVPA was associated with greater decrease in HDL cholesterol and increase in
clustered cardiometabolic risk, waist circumference and fasting glucose,
independent of change in SB. Greater decrease in CRF was associated with more
detrimental change in clustered cardiometabolic risk and all individual
components. Change in CRF mediated the associations of change in SB and MVPA with
change in clustered cardiometabolic risk, waist circumference and, only for MVPA,
HDL cholesterol. Change in waist circumference mediated the associations between
change in CRF and change in clustered cardiometabolic risk, fasting glucose, HDL
cholesterol and triglycerides. CONCLUSIONS: A combination of decreasing SB and
increasing MVPA, resulting in positive change in CRF, is likely to be most
beneficial towards cardiometabolic health.
PMID- 27491780
TI - Forward genetic screen of human transposase genomic rearrangements.
AB - BACKGROUND: Numerous human genes encode potentially active DNA transposases or
recombinases, but our understanding of their functions remains limited due to
shortage of methods to profile their activities on endogenous genomic substrates.
RESULTS: To enable functional analysis of human transposase-derived genes, we
combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase
1 (HPRT1) screening with massively parallel paired-end DNA sequencing and
structural variant genome assembly and analysis. Here, we report the HPRT1
mutational spectrum induced by the human transposase PGBD5, including PGBD5
specific signal sequences (PSS) that serve as potential genomic rearrangement
substrates. CONCLUSIONS: The discovered PSS motifs and high-throughput forward
chemical genomic screening approach should prove useful for the elucidation of
endogenous genome remodeling activities of PGBD5 and other domesticated human DNA
transposases and recombinases.
PMID- 27491781
TI - Kawasaki disease incidence at Chandigarh, North India, during 2009-2014.
AB - The aim of this study was to estimate incidence of Kawasaki disease (KD) in
Chandigarh, North India, during 2009-2014. Diagnosis of KD was based on American
Heart Association guidelines. Records of all children diagnosed with KD below 15
years at a large tertiary care referral centre from North India for paediatric
immunology were analysed from January 2009 to December 2014. Children residing in
Chandigarh were identified. Incidence rates were calculated based on population
of Chandigarh in National Census 2011. Methodology was similar to our previously
reported study from 1994 to 2008. Incidence of KD in children below 5 was also
computed. A total of 258 children were diagnosed to have KD. Of these, 54 (43
boys, 11 girls) resided in Chandigarh. Coronary artery abnormalities on
echocardiography were noted in 6. Incidence rate varied between 1.11 (in 2012)
and 4.71/100,000 children below 15 (in 2009). In children below 5, incidence rate
varied between 1.0 (in 2012) and 9.1/100,000 (in 2009). Peak incidence of KD was
in third year of life. There was clustering of cases in February, April, June and
October with a nadir in July. While the overall number of KD cases has increased,
the 2009-2014 Chandigarh incidence is comparable to our previous figures. Our
study is based on hospitalized children with KD and may be missing patients
diagnosed elsewhere but that number is likely to be small. Further, patients in
whom the diagnosis has never been made would also be missed. Median age at
diagnosis has reduced as compared to our previous study. This is probably a
reflection of increased awareness about KD amongst paediatricians and physicians
in the region as a result of which the proportion of infants and young children
diagnosed to have KD has shown a significant increase. Seasonal pattern of
occurrence of KD is consistent with our previous observation.
PMID- 27491782
TI - Safety and efficacy of a novel linear staple device with bioabsorbable
polyglicolic acid felt in laparoscopic colorectal surgery.
AB - INTRODUCTION: Laparoscopic surgery is widely used for the treatment of colorectal
cancer, but it is often associated with postoperative anastomotic complications.
Generally, gastrointestinal anastomosis for colorectal surgery is performed using
mechanical anastomosis with a double stapling technique. Using the automatic
suture device with bioabsorbable polyglycolic acid (PGA) felt is expected to
adequately reinforce staple lines on fragile tissue, helping to prevent
anastomotic complications, including leakage. METHODS: This study included 17
patients who underwent laparoscopic surgery after a diagnosis of colorectal
cancer. The rectosigmoidal colon was resected toward the dentate line with a
novel automatic PGA-felt suture device. RESULTS: None of the patients had any
postoperative bleeding, and none developed grade III or higher postoperative
complications based on the Clavien-Dindo classification. When the sigmoid colon,
rectosigmoid, or rectum was anastomosed, holding the excess portion of the PGA
felt, stapled with the automatic PGA-felt suture device, allowed us to adequately
maneuver the part of the colon or rectum to be anastomosed. With this technique,
we could easily and safely insert and remove the automatic anastomotic device.
When the lower rectum was resected in a planned, two-step operation, the
orientation of the PGA felt helped to determine the direction in which the
automatic suture device was to be inserted in the second step. Thus, the resected
rectum could easily be stapled in a straight line. CONCLUSION: The automatic PGA
felt suture device is safe and effective for colorectal resections and
anastomoses.
PMID- 27491783
TI - Gastroesophageal Junction Tumors.
PMID- 27491784
TI - Utility of Clinical Breast Examinations in Detecting Local-Regional Breast Events
After Breast-Conservation in Women with a Personal History of High-Risk Breast
Cancer.
AB - BACKGROUND: Although breast cancer follow-up guidelines emphasize the importance
of clinical examinations, prior studies suggest a small fraction of local
regional events occurring after breast conservation are detected by examination
alone. Our objective was to examine how local-regional events are detected in a
contemporary, national cohort of high-risk breast cancer survivors. METHODS: A
stage-stratified sample of stage II/III breast cancer patients diagnosed in 2006
2007 (n = 11,099) were identified from 1217 facilities within the National Cancer
Data Base. Additional data on local-regional and distant breast events, method of
event detection, imaging received, and mortality were collected. We further
limited the cohort to patients with breast conservation (n = 4854). Summary
statistics describe local-regional event rates and detection method. RESULTS:
Local-regional events were detected in 5.5 % (n = 265) of patients. Eighty-three
percent were ipsilateral or contralateral in-breast events, and 17 % occurred
within ipsilateral lymph nodes. Forty-eight percent of local-regional events were
detected on asymptomatic breast imaging, 29 % by patients, and 10 % on clinical
examination. Overall, 0.5 % of the 4854 patients had a local-regional event
detected on examination. Examinations detected a higher proportion of lymph node
events (8/45) compared with in-breast events (18/220). No factors were associated
with method of event detection. DISCUSSION: Clinical examinations, as an adjunct
to screening mammography, have a modest effect on local-regional event detection.
This contradicts current belief that examinations are a critical adjunct to
mammographic screening. These findings can help to streamline follow-up care,
potentially improving follow-up efficiency and quality.
PMID- 27491785
TI - Primary Extremity Soft Tissue Sarcomas: Does Local Control Impact Survival?
AB - BACKGROUND: The objective of this study was to evaluate the adequate margin in
the local treatment of extremity soft tissue sarcomas (ESTS) and understand the
relationship between local control and overall survival (OS). METHODS: All
consecutive patients treated for a primary ESTS at a single center from 1993 to
2012 were reviewed. RESULTS: In all, 531 patients were included. Twelve (2 %)
underwent a first-line amputation. The resections were R0/R1/not available in 434
(82 %), 92 (17 %), and 5 patients (1 %). The median tumor size was 8 cm, and the
tumor grades were 1 (n = 132), 2 (n = 201), and 3 (n = 195). The median size of
the minimal margin was 2 mm on fixed specimen. Preop or postop chemotherapy was
administered to 222 patients, and 414 received radiotherapy. With a median follow
up period of 7 years, the 5-year actuarial local recurrence (LR) rate and OS were
8 % (95 % CI, 6-11 %) and 80 % (95 % CI, 76-83 %). Predictors of worse OS were
grade 3, leiomyosarcoma, male gender, and age >60 years, whereas tumor size,
margin status, and LR were not. Among patients requiring re-excision (n = 252),
the presence of residual cells correlated with OS but not LR. After preoperative
treatment, a percentage of residual cells >=10 % correlated with OS but not LR.
In the multivariate analysis, specific subtypes (epithelioid sarcoma and
myxofibrosarcoma) and margin size <1 mm correlated with LR, whereas grade and the
tissue constituting the surgical margins did not. CONCLUSIONS: Specific subtypes
and surgical margin size <1 mm were correlated with a higher LR. Neither the
margin status nor LR affect OS.
PMID- 27491787
TI - Iron(III)-Catalyzed Ring-Closing Carbonyl-Olefin Metathesis.
AB - Recent developments in catalytic carbonyl-olefin metathesis are summarized in
this Highlight. Schindler and co-workers have reported that the environmentally
benign FeCl3 catalyst promotes ring-closing carbonyl-olefin metathesis (RCCOM) in
high yield under very mild conditions.
PMID- 27491788
TI - [Not Available].
PMID- 27491786
TI - Thalamus Degeneration and Inflammation in Two Distinct Multiple Sclerosis Animal
Models.
AB - There is a broad consensus that multiple sclerosis (MS) represents more than an
inflammatory disease: it harbors several characteristic aspects of a classical
neurodegenerative disorder, i.e., damage to axons, synapses, and nerve cell
bodies. While several accepted paraclinical methods exist to monitor the
inflammatory-driven aspects of the disease, techniques to monitor progression of
early and late neurodegeneration are still in their infancy and have not been
convincingly validated. It was speculated that the thalamus with its multiple
reciprocal connections is sensitive to inflammatory processes occurring in
different brain regions, thus acting as a "barometer" for diffuse brain
parenchymal damage in MS. To what extent the thalamus is affected in commonly
applied MS animal models is, however, not known. In this article we describe
direct and indirect damage to the thalamus in two distinct MS animal models. In
the cuprizone model, we observed primary oligodendrocyte stress which is followed
by demyelination, microglia/astrocyte activation, and acute axonal damage. These
degenerative cuprizone-induced lesions were found to be more severe in the
lateral compared to the medial part of the thalamus. In MOG35-55-induced EAE, in
contrast, most parts of the forebrain, including the thalamus were not directly
involved in the autoimmune attack. However, important thalamic afferent fiber
tracts, such as the spinothalamic tract were inflamed and demyelinated on the
spinal cord level. Quantitative immunohistochemistry revealed that this spinal
cord inflammatory-demyelination is associated with neuronal loss within the
target region of the spinothalamic tract, namely the sensory ventral
posterolateral nucleus of the thalamus. This study highlights the possibility of
trans-neuronal degeneration as one mechanism of secondary neuronal damage in MS.
Further studies are now warranted to investigate involved cell types and cellular
mechanisms.
PMID- 27491789
TI - Defining Known Drug Space Using DFT.
AB - A density functional theory (DFT) study was performed on a collection of
clinically approved drugs, or Known Drug Space (KDS), to determine the
statistical distribution of four properties: dipole moment (DM), polarisability
(POL), ionisation potential (IP) and electron affinity (EA). The DM and POL are
linked to cell permeability of drugs whereas IP and EA reflect their redox
stability thus ease of metabolism. A benchmarking exercise showed a good
correlation between experimental values and their predicted counterparts. It was
found that KDS occupies the volume of chemical space defined by: DM<=10 D,
POL<=68 A(3) , IP 6.0-9.0 V and EA-1.5-2.0 eV. Only 16 % of the drugs are outside
one or more of these parameters. Three categories based on known oral absorption
and bioavailability (low/medium/high) were established and compared.
Predominately, drugs designated as 'low' were found outside the established
parameters. The properties were compared with mainstream molecular descriptors
and a strong correlation was seen for POL to MW (r(2) =0.899), which can explain
the success of the latter since POL reflects the ability of molecules to interact
with polar and non-polar environments such as water and interior of a membrane.
PMID- 27491790
TI - The Comparison of the Combined Toxicity between Gram-negative and Gram-positive
Bacteria: a Case Study of Antibiotics and Quorum-sensing Inhibitors.
AB - Quorum-sensing inhibitors (QSIs) are being used increasingly in diverse fields,
and are likely to end up in the environment, where they may encounter the
antibiotics and consequently cause joint effects on biological systems. However,
the potential joint effects of QSIs and antibiotics have received little
attention. In this study, the joint effects of antibiotics, represented by
sulfonamides (SAs) and penicillin, as well as three potential QSIs, were
investigated using both Gram-negative (Escherichia coli, E. coli) and Gram
positive bacteria (Bacillus subtilis, B. subtilis). It was found that E. coli
tend to be more sensitive to the individual drugs than B. subtilis, whereas the
joint effects on the two bacteria showed no difference regarding the same
combination of antibiotics and QSIs. In general, SAs presented additive effects
with gamma-Valerolactone and 2-Pyrrolidinone, but antagonistic effects with L-(+)
Prolinol; penicillin exhibited antagonistic effects with all three QSIs.
Moreover, it was found that the rate of resistance in E. coli against the
individual antibiotics was reduced through the addition of the QSIs, which
suggests a promising use of the QSIs in the bacterial infection treatment. This
study also offers a valuable reference for the risk assessment of the antibiotics
and QSIs in the real environment.
PMID- 27491791
TI - Machine Learning Estimation of Atom Condensed Fukui Functions.
AB - To enable the fast estimation of atom condensed Fukui functions, machine learning
algorithms were trained with databases of DFT pre-calculated values for ca.
23,000 atoms in organic molecules. The problem was approached as the ranking of
atom types with the Bradley-Terry (BT) model, and as the regression of the Fukui
function. Random Forests (RF) were trained to predict the condensed Fukui
function, to rank atoms in a molecule, and to classify atoms as high/low Fukui
function. Atomic descriptors were based on counts of atom types in spheres around
the kernel atom. The BT coefficients assigned to atom types enabled the
identification (93-94 % accuracy) of the atom with the highest Fukui function in
pairs of atoms in the same molecule with differences >=0.1. In whole molecules,
the atom with the top Fukui function could be recognized in ca. 50 % of the cases
and, on the average, about 3 of the top 4 atoms could be recognized in a
shortlist of 4. Regression RF yielded predictions for test sets with R(2) =0.68
0.69, improving the ability of BT coefficients to rank atoms in a molecule. Atom
classification (as high/low Fukui function) was obtained with RF with sensitivity
of 55-61 % and specificity of 94-95 %.
PMID- 27491792
TI - Predictive Models for Halogen-bond Basicity of Binding Sites of Polyfunctional
Molecules.
AB - Halogen bonding (XB) strength assesses the ability of an electron-enriched group
to be involved in complexes with polarizable electrophilic halogenated or
diatomic halogen molecules. Here, we report QSPR models of XB of particular
relevance for an efficient screening of large sets of compounds. The basicity is
described by pKBI2 , the decimal logarithm of the experimental 1 : 1 (B : I2 )
complexation constant K of organic compounds (B) with diiodine (I2 ) as a
reference halogen-bond donor in alkanes at 298 K. Modeling involved ISIDA
fragment descriptors, using SVM and MLR methods on a set of 598 organic
compounds. Developed models were then challenged to make predictions for an
external test set of 11 polyfunctional compounds for which unambiguous assignment
of the measured effective complexation constant to specific groups out of the
putative acceptor sites is not granted. At this stage, developed models were used
to predict pKBI2 of all putative acceptor sites, followed by an estimation of the
predicted effective complexation constant using the ChemEqui program. The best
consensus models perform well both in cross-validation (root mean squared error
RMSE=0.39-0.47 logKBI2 units) and external predictions (RMSE=0.49). The SVM
models are implemented on our website (http://infochim.u
strasbg.fr/webserv/VSEngine.html) together with the estimation of their
applicability domain and an automatic detection of potential halogen-bond
acceptor atoms.
PMID- 27491793
TI - Pharmacophore-Map-Pick: A Method to Generate Pharmacophore Models for All Human
GPCRs.
AB - GPCR-based drug discovery is hindered by a lack of effective screening methods
for most GPCRs that have neither ligands nor high-quality structures. With the
aim to identify lead molecules for these GPCRs, we developed a new method called
Pharmacophore-Map-Pick to generate pharmacophore models for all human GPCRs. The
model of ADRB2 generated using this method not only predicts the binding mode of
ADRB2-ligands correctly but also performs well in virtual screening. Findings
also demonstrate that this method is powerful for generating high-quality
pharmacophore models. The average enrichment for the pharmacophore models of the
15 targets in different GPCR families reached 15-fold at 0.5 % false-positive
rate. Therefore, the pharmacophore models can be applied in virtual screening
directly with no requirement for any ligand information or shape constraints. A
total of 2386 pharmacophore models for 819 different GPCRs (99 % coverage
(819/825)) were generated and are available at http://bsb.kiz.ac.cn/GPCRPMD.
PMID- 27491794
TI - Variable resistance to freezing and thawing of CD34-positive stem cells and
lymphocyte subpopulations in leukapheresis products.
AB - BACKGROUND AIMS: Leukapheresis products for hematopoietic stem cell
transplantation can be cryopreserved for various indications. Although it is
known that CD34(+) cells tolerate cryopreservation well, a significant loss of
CD3(+) cells has been observed, which has been ascribed to several factors,
including transport, storage conditions and granulocyte-colony stimulating factor
(G-CSF) administration. METHODS: To assess the tolerance of CD34(+) cells and
lymphocyte subpopulations for cryopreservation and thawing, the post-thaw
recoveries of CD34(+) cells, CD3(+)CD4(+) cells, CD3(+)CD8(+) cells, CD19(+)
cells and CD16(+)CD56(+) cells were determined in 90 cryopreserved apheresis
products, among which 65 were from G-CSF-mobilized donors, and 34 from unrelated
donors that underwent transport before cryopreservation at our center. A
controlled rate freezer and 5% dimethyl sulfoxide were used for cryopreservation.
RESULTS: We could detect statistically significant differences for CD34(+) cell
recovery (93.0 +/- 20.7%) when compared to CD3(+)CD4(+) cell (83.1 +/- 15.4%, P =
0.014), and CD3(+)CD8(+) cell recovery (83.3 +/- 13.9%, P = 0.001). Similarly,
CD19(+) cell recovery (98.6 +/- 15.1%) was higher than CD3(+)CD4(+) cell (P = 2.5
* 10(-7)) and CD3(+)CD8(+) cell recovery (P = 1.2 * 10(-8)). Post-thaw recovery
rates of all cell populations were not impaired in G-CSF-mobilized products
compared with non-mobilized products nor in unrelated compared with related donor
products. DISCUSSION: Our data suggest a lower tolerance of CD3(+) cells for
cryopreservation and demonstrate that freezing-thawing resistance thawing is cell
specific and independent from other factors that affect post-thaw recovery of
cryopreserved cells. Thus, a clinical consequence may be the monitoring of post
thaw CD3(+) cell doses of cryopreserved products, such as donor lymphocyte
infusions.
PMID- 27491795
TI - Metabolic fate of adenine in red blood cells during storage in SAGM solution.
AB - BACKGROUND: Red blood cells (RBCs) are routinely stored and transfused worldwide.
Recently, metabolomics have shown that RBCs experience a three-phase metabolic
decay process during storage, resulting in the definition of three distinct
metabolic phenotypes, occurring between Days 1 and 10, 11 and 17, and 18 and 46.
Here we use metabolomics and stable isotope labeling analysis to study adenine
metabolism in RBCs. STUDY DESIGN AND METHODS: A total of 6 units were prepared in
SAGM or modified additive solutions (ASs) containing 15 N5 -adenine. Three of
them were spiked with 15 N5 -adenine on Days 10, 14, and 17 during storage. Each
unit was sampled 10 times spanning Day 1 to Day 32. At each time point metabolic
profiling was performed. RESULTS: We increased adenine concentration in the AS
and we pulsed the adenine concentration during storage and found that in both
cases the RBCs' main metabolic pathways were not affected. Our data clearly show
that RBCs cannot consume adenine after 18 days of storage, even if it is still
present in the storage solution. However, increased levels of adenine influenced
S-adenosylmethionine metabolism. CONCLUSION: In this work, we have studied in
detail the metabolic fate of adenine during RBC storage in SAGM. Adenine is one
of the main substrates used by RBCs, but the metabolic shift observed during
storage is not caused by an absence of adenine later in storage. The rate of
adenine consumption strongly correlated with duration of storage but not with the
amount of adenine present in the AS.
PMID- 27491796
TI - TRPV4 mediates afferent pathways in the urinary bladder. A spinal c-fos study
showing TRPV1 related adaptations in the TRPV4 knockout mouse.
AB - The role of transient receptor potential vanilloid subtype 4 (TRPV4) channels in
urinary bladder afferent neural pathways was investigated using spinal c-fos
measurements in mice. Anesthetized wild type and TRPV4 knockout (-/-) mice
underwent noxious bladder distention and treatment with either intravesical
instillation with lipopolysaccharide (LPS), or the TRPV1 agonist resiniferatoxin
(RTX), vehicle or an intraperitoneal injected TRPV4 antagonist (HC067047). Mice
underwent paraformaldehyde perfusion for rapid fixation and L6-S1 spinal cord
sections were removed followed by immunohistochemical staining for c-fos. A
number of c-fos expressing neurons in the dorsal horns of L6-S1 spinal cord
transections were quantified. Groups were compared using univariate ANOVA. Even
with the absence of bladder inflammation on H&E, the TRPV4 -/- mice still have a
significant twofold higher c-fos expression (n = 39, SD 2) after noxious bladder
distention compared to wild type mice (n = 20, SD 3). A twofold increase in c-fos
expression was observed after LPS treatment in wild types (n = 42, SD 5), but no
increase was seen in TRPV4 -/- mice (n = 42, SD 2). After desensitization of
primary afferent C-nerve fibers with RTX, c-fos expression in TRPV4-/- mice
decreased significantly (threefold) (n = 12, SD 4). Results imply that TRPV4
channels are important for bladder afferent signaling. TRPV4 -/- mice bladders
generate more noxious sensory output, which is predominantly mediated through
TRPV1 expressing high threshold nerve fibers. This study reveals TRPV1 related
adaptive changes in afferent pathways of the TRPV4 -/- mouse. We propose that
this effect is caused by a congenital impairment of low threshold nerves that
mediate normal bladder filling sensations.
PMID- 27491798
TI - Development in attention functions and social processing: Evidence from the
Attention Network Test.
AB - According to the attention network approach, attention is best understood in
terms of three functionally and neuroanatomically distinct networks - alerting,
orienting, and executive attention. Recent findings showed that social
information influences the efficiency of these networks in adults. Using some
social and non-social variants of the Attentional Network Test (ANT), this study
was aimed to evaluate the development of the three attention networks in
childhood, also assessing the development of the ability to manage social or non
social conflicting information. Sixty-six children (three groups of 6, 8, and 10
years of age) performed three variants of the original ANT, using fish,
schematic, or real faces looking to the left or right as target and flanker
stimuli. Results showed an improvement from 6 to 8 and 10 years of age in
reaction time (RT) and accuracy, together with an improvement of executive
control and a decrement in alerting. These developmental changes were not unique
to social stimuli, and no differences were observed between social and no-social
variants of the ANT. However, independently from the age of the children, a real
face positively affected the executive control (as indexed by RTs) as compared to
both a schematic face and a fish. Findings of this study suggest that attentional
networks are still developing from 6 to 10 years of age and underline the
importance of face information in modulating the efficiency of executive control.
Statement of contribution What is already known? Younger children made more
errors and slower reaction times (RTs) than older children, in line with the
majority of the past selective attention studies. Younger children showed both
greater conflict and alerting effect than older children. The prediction that
younger children would display larger interference effects than older children
was supported. What does this study add? Extending the findings observed in
adults and children, independently from their age, demonstrated greater cognitive
interference (i.e., slower RTs and higher percentage of errors to incongruent
relative to congruent conditions) when fish and schematic faces were presented
than when photographs of real faces were used as stimuli. Like adults, children
have a greater ability in the control of social information as compared to non
social information. These results seem to indicate that the ability to handle
social conflicts proceeds in parallel with the ability to manage non-social
conflicting information.
PMID- 27491797
TI - Development and psychometric evaluation of a condom use self-efficacy measure in
Spanish and English.
AB - BACKGROUND: Condom self-efficacy is an important construct for HIV/STI prevention
and intervention. A psychometrically sound measure of the self-efficacy for using
condoms that has been designed for Hispanic women to respond in Spanish or
English is needed. OBJECTIVES: The goal of this study was to develop and evaluate
a brief self-report measure of condom use self-efficacy. METHODS: We developed a
15-item measure of condom use self-efficacy based on expert knowledge of
measurement and HIV/STI prevention with Hispanic women using a translation-back
translation approach. Participants were 320 Hispanic women from the Southeastern
US. RESULTS: Internal consistency of the full measure was 92. A short form of the
instrument with a subset of five items also had acceptable internal consistency,
alpha = .80, and was significantly correlated with the full scale, rs = .93, p <
.001. A single latent factor explained 9-48% of the variation in these items.
Evidence of construct validity of the short form was provided by correlations of
the scale with two self-report measures of condom use: rs = .34** with condom
use, rs = .37** with condom use during vaginal sex. CONCLUSIONS: Either the full
measure or the five-item measure could be used in studies where condom use is an
important behavioral outcome, such as evaluating prevention interventions, with
Hispanic women. Future studies should examine the performance of this measure
with other groups, including Hispanic men and members of other ethnic and
language groups.
PMID- 27491800
TI - Fatal cobalt toxicity after total hip arthroplasty revision for fractured ceramic
components.
AB - CONTEXT: Post-arthroplasty metallosis, which refers to metallic corrosion and
deposition of metallic debris in the periprosthetic soft tissues of the body, is
an uncommon complication. Systemic cobalt toxicity post-arthroplasty is extremely
rare. The few known fatal cases of cobalt toxicity appear to be a result of
replacing shattered ceramic heads with metal-on-metal or metal-on-polyethylene
implants. Friction between residual shards of ceramic and cobalt-chromium
implants allows release of cobalt into the synovial fluid and bloodstream,
resulting in elevated whole blood cobalt levels and potential toxicity. CASE
DETAILS: This is a single patient chart review of a 60-year-old woman with prior
ceramic-on-ceramic right total hip arthroplasty complicated by fractured ceramic
components and metallosis of the joint. She underwent synovectomy and revision to
a metal-on-polyethylene articulation. Ten months post-revision, she presented to
the emergency department (ED) with right hip pain, dyspnea, worsening hearing
loss, metallic dysgeusia, and weight loss. Chest CTA revealed bilateral pulmonary
emboli (PE), and echocardiogram revealed new cardiomyopathy with global left
ventricular hypokinesis with an ejection fraction (EF) of 35-40% inconsistent
with heart strain from PE. Whole blood cobalt level obtained two days into her
admission was 424.3 mcg/L and 24-h urine cobalt level was 4830.5 mcg/L. Although
the patient initially clinically improved with regard to her PE and was
discharged to home on hospital day 5, she returned 10 days later with a right hip
dislocation and underwent closed reduction of the hip. The patient subsequently
decompensated, developing cardiogenic shock, and respiratory failure. She went
into pulseless electrical activity (PEA) and expired. Autopsy revealed an
extensive metallic effusion surrounding the right hip prosthesis that tested
positive for cobalt (41,000 mcg/L). There was also cobalt in the heart muscle
tissue (2.5 mcg/g). A whole blood cobalt level obtained two days before she
expired was 641.6 mcg/L. DISCUSSION: This is a case of fatal cobalt-induced
cardiomyopathy in a patient whose ceramic components of a total hip arthroplasty
fractured causing metallosis with worsening cobalt toxicity. We recommend that
when a fractured device is revised with a prosthesis with cobalt-chromium
components, whole blood and urine cobalt measurements should be obtained and
periodically monitored to evaluate for rising concentrations. Providers should be
aware of clinical signs and symptoms of cobalt toxicity in patients who have
prostheses with cobalt-chromium components. If suspected, toxicology and
orthopedics should be involved for possible chelation and removal of the
prosthesis.
PMID- 27491799
TI - Consciousness and cortical responsiveness: a within-state study during non-rapid
eye movement sleep.
AB - When subjects become unconscious, there is a characteristic change in the way the
cerebral cortex responds to perturbations, as can be assessed using transcranial
magnetic stimulation and electroencephalography (TMS-EEG). For instance, compared
to wakefulness, during non-rapid eye movement (NREM) sleep TMS elicits a larger
positive-negative wave, fewer phase-locked oscillations, and an overall simpler
response. However, many physiological variables also change when subjects go from
wake to sleep, anesthesia, or coma. To avoid these confounding factors, we
focused on NREM sleep only and measured TMS-evoked EEG responses before awakening
the subjects and asking them if they had been conscious (dreaming) or not. As
shown here, when subjects reported no conscious experience upon awakening, TMS
evoked a larger negative deflection and a shorter phase-locked response compared
to when they reported a dream. Moreover, the amplitude of the negative deflection
a hallmark of neuronal bistability according to intracranial studies-was
inversely correlated with the length of the dream report (i.e., total word
count). These findings suggest that variations in the level of consciousness
within the same physiological state are associated with changes in the underlying
bistability in cortical circuits.
PMID- 27491801
TI - In vivo imaging of DNA double-strand break induced telomere mobility during
alternative lengthening of telomeres.
AB - Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR)
requires mobilization of chromatin for homology searches that allow interaction
of the sequence to be repaired and its template DNA. Here we describe a system to
rapidly induce DSBs at telomeres and track their movement, as well as a semi
automated workflow for quantitative analysis. We have successfully used this
approach to show that DSBs targeted to telomeres in cells utilizing the
alternative lengthening of telomeres (ALT) mechanism increase their diffusion and
subsequent long-range directional movement to merge with telomeres on other
chromosomes. These methods are simple to implement and are compatible with almost
any cell line or in vivo microscopy setup. The magnitude of DSB-induced telomere
mobility allows the investigator to easily test for factors regulating telomere
mobility during ALT.
PMID- 27491802
TI - Lens opacity detection for serious posterior subcapsular cataract.
AB - Cataract leads to visual impairment. Among different types of cataract, posterior
subcapsular cataract (PSC) can develop rapidly and surgery is usually needed. An
approach to detect PSC opacities in retro-illumination images is proposed.
Watershed and Markov random fields (MRF) method are employed to opacities in
anterior retro-illumination images. It results in a mixture of PSC, cortical
opacities and noise. Then, information in both anterior and posterior retro
illumination images is utilized. Two features are extracted to identify PSC: mean
gradient comparison (MGC) between anterior and posterior retro-illumination
images, and spatial location. This is the first time that comparison between
anterior and posterior retro-illumination images is proposed and MGC is proposed
as the feature of comparison in PSC detection. Experiments show that the
sensitivity and specificity of PSC screening is 91.2 and 90.1 %, respectively,
based on the 519 pairs of testing images. To the best of our knowledge, it is the
best performance reported in automatic detection of PSC. Compared with the
methods in the literatures, considerable improvement is achieved when there are
large areas of PSC opacities.
PMID- 27491803
TI - Finite element model of the impaction of a press-fitted acetabular cup.
AB - Press-fit surgical procedures aim at providing primary stability to acetabular
cup (AC) implants. Impact analysis constitutes a powerful approach to retrieve
the AC implant insertion properties. The aim of this numerical study was to
investigate the dynamic interaction occurring between the hammer, the ancillary
and bone tissue during the impact and to assess the potential of impact analysis
to retrieve AC implant insertion conditions. A dynamic two-dimensional
axisymmetric model was developed to simulate the impaction of the AC implant into
bone tissue assuming friction at the bone-implant interface and large
deformations. Different values of interference fit (from 0.5 to 2 mm) and impact
velocities (from 1 to 2 m.s-1) were considered. For each configuration, the
variation of the force applied between the hammer and the ancillary was analyzed
and an indicator I was determined based on the impact momentum of the signal. The
simulated results are compared to the experiments. The value of the polar gap
decreases with the impact velocity and increases with the interference fit. The
bone-implant contact area was significantly correlated with the resonance
frequency (R 2 = 0.94) and the indicator (R 2 = 0.95). The results show the
potential of impact analyses to retrieve the bone-implant contact properties.
PMID- 27491804
TI - Study of a water-soluble fluorescent sensor based on the Eu(III) pefloxacin
complex.
AB - The antibiotic type organic structure pefloxacin binds well with europium (III)
ions as a useful scaffold for assembling optical probes and allows energy
transfer from ligand to metal ions through coordination linkages. This water
soluble chemosensor demonstrated significant 'off-on (red)' changes from an
alkaline to a neutral environment (pH 14-8). The emission changed from red to
blue under acidic conditions (pH 7-2). The whole process was completely
reversible and effective within the pH range 2 to 14. Moreover, this probe system
exhibited distinct luminescence quenching upon the addition of Cu2+ or Fe3+ .
This general modular route will permit easy detection and the concept can be
extended to a variety of quinolones for sensing purposes.
PMID- 27491805
TI - Distribution of inflammation and association between active and chronic
alterations within the endometrium of dairy cows.
AB - Objectives of this study were twofold: (i) to assess the association between
polymorphonuclear (PMN) counts and chronic alterations within the bovine
endometrium and (ii) to determine the distribution of inflammation throughout the
endometrium of clinically healthy dairy cows. Holstein-Friesian cows (n = 32)
from a single dairy farm were selected for this experiment. Before slaughtering,
a complete reproductive examination was performed to discard any type of clinical
disease. After slaughtering, reproductive tracts were collected, and the
endometrium was sampled at 8 pre-defined locations. At each location, endometrial
biopsies (EBs) and cytology (CY) samples were harvested. Histopathology samples
were stained with haematoxylin-eosin (EB-HE) and naphthol-AS-D-chloroacetate
esterase (EB-naphthol), while CY samples were stained with Wright-Giemsa. In the
EB-HE samples, parameters assessed were epithelium height, mononuclear cells
infiltration, lymphocytic aggregates, periglandular fibrosis, angiosclerosis and
haemorrhage. In EB-naphthol and CY slides, PMNs counts were evaluated. Binomial
logistic regression was used to assess the association between the number of PMNs
present in both the EB-naphthol and CY samples and alterations identified in the
EB-HE samples and to analyse the distribution of the histopathological
alterations (EB-HE). A Poisson mixed-effect model was used to analyse the
distribution of PMNs within the endometrium. A significant positive association
was found between the PMN counts and the mononuclear cells infiltration. The
presence of erythrocytes was associated with higher odds to detect PMNs in the
stratum compactum. Significantly, higher infiltration of PMNs and mononuclear
cells were detected in the uterine body and the right horn region. Concluding, CY
is a technique that allows the evaluation of PMN counts and therefore only
evaluates active inflammation. A complete assessment of endometrial health can
only be obtained using EB. To optimize the sensitivity to diagnose endometrial
inflammation in cows, adjacencies of the corpus uteri should be considered as the
preferred region to harvest samples.
PMID- 27491806
TI - Promoting women's health in an era of globalization: a South Asian perspective.
AB - Promoting the health of women requires an understanding of the full range of
factors shaping their health, including globalization. Focusing on South Asia, I
outline some of the critical global women's health issues that warrant further
attention by health promotion researchers. I discuss the inadequacy of
international approaches for improving the health of South Asian women,
occupational health hazards associated with global industries targeting women,
new forms of gender based violence, gendered ethical challenges arising as global
and local forces collide and the rise of transnational feminist networks that can
be harnessed for advancing women's health across the region.
PMID- 27491807
TI - The Latin America and the Caribbean search strategy proposal.
AB - Latin America and the Caribbean's public health literature is not widely
recognized. Science in this region has even been compared to a night sky with
just a few specks of light. To make those lights as reachable as possible, we
developed the Latin America and the Caribbean Search Strategy (LACSS). This is a
new method to utilize our region's health promotion results within
MEDLINE/PubMed. In contrast to a typical MeSH query, LACSS retrieves up to six
times more publication results regarding non-communicable diseases, neglected
tropical diseases, injuries and other important public health relevant topics in
the region. We believe that global health promotion will be improved in this
region by improving its visibility, and this search strategy will contribute to
this.
PMID- 27491808
TI - The proposal of philosophical basis of the health care system.
AB - The studies of health care systems are conducted intensively on various levels.
They are important because the systems suffer from numerous pathologies. The
health care is analyzed, first of all, in economic aspects but their
functionality in the framework of systems theory is studied, as well. There are
also attempts to work out some general values on which health care systems should
be based. Nevertheless, the aforementioned studies, however, are fragmentary
ones. In this paper holistic approach to the philosophical basis of health care
is presented. The levels on which the problem can be considered are specified
explicitly and relations between them are analyzed, as well. The philosophical
basis on which the national health care systems could be based is proposed.
Personalism is the basis for the proposal. First of all, the values, that are
derived from the personalistic philosophy, are specified as the basic ones for
health care systems. Then, general organizational and functional properties of
the system are derived from the assumed values. The possibility of adaptation of
solutions from other fields of social experiences are also mentioned. The
existing health care systems are analyzed within the frame of the introduced
proposal.
PMID- 27491809
TI - Genetic events in the progression of adenoid cystic carcinoma of the breast to
high-grade triple-negative breast cancer.
AB - Adenoid cystic carcinoma of the breast is a rare histological type of triple
negative breast cancer with an indolent clinical behavior, often driven by the
MYB-NFIB fusion gene. Here we sought to define the repertoire of somatic genetic
alterations in two adenoid cystic carcinomas associated with high-grade triple
negative breast cancer. The different components of each case were subjected to
copy number profiling and massively parallel sequencing targeting all exons and
selected regulatory and intronic regions of 488 genes. Reverse transcription PCR
and fluorescence in situ hybridization were employed to investigate the presence
of the MYB-NFIB translocation. The MYB-NFIB fusion gene was detected in both
adenoid cystic carcinomas and their associated high-grade triple-negative breast
cancer components. Although the distinct components of both cases displayed
similar patterns of gene copy number alterations, massively parallel sequencing
analysis revealed intratumor genetic heterogeneity. In case 1, progression from
the trabecular adenoid cystic carcinoma to the high-grade triple-negative breast
cancer was found to involve clonal shifts with enrichment of mutations affecting
EP300, NOTCH1, ERBB2 and FGFR1 in the high-grade triple-negative breast cancer.
In case 2, a clonal KMT2C mutation was present in the cribriform adenoid cystic
carcinoma, solid adenoid cystic carcinoma and high-grade triple-negative breast
cancer components, whereas a mutation affecting MYB was present only in the solid
and high-grade triple-negative breast cancer areas and additional three mutations
targeting STAG2, KDM6A and CDK12 were restricted to the high-grade triple
negative breast cancer. In conclusion, adenoid cystic carcinomas of the breast
with high-grade transformation are underpinned by the MYB-NFIB fusion gene and,
akin to other forms of cancer, may be constituted by a mosaic of cancer cell
clones at diagnosis. The progression from adenoid cystic carcinoma to high-grade
triple-negative breast cancer of no special type may involve the selection of
neoplastic clones and/or the acquisition of additional genetic alterations.
PMID- 27491810
TI - Molecular genetic heterogeneity in undifferentiated endometrial carcinomas.
AB - Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly
aggressive subtypes of uterine cancer, not well characterized at a molecular
level. To investigate whether dedifferentiated carcinomas carry molecular genetic
alterations similar to those of pure undifferentiated carcinomas, and to gain
insight into the pathogenesis of these tumors, we selected a cohort of 18
undifferentiated endometrial carcinomas, 8 of them with a well-differentiated
endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and
studied them by immunohistochemistry and massive parallel and Sanger sequencing.
Whole-exome sequencing of the endometrioid and undifferentiated components, as
well as normal myometrium, was also carried out in one case. According to The
Cancer Genome Atlas classification, we distributed 95% of the undifferentiated
carcinomas in this series as follows: (a) hypermutated tumors with loss of any
mismatch repair protein expression and microsatellite instability (eight cases,
45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of
POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors
group exhibiting only TP53 mutations and high number of alterations detected by
FISH (two cases, 11%); and (d) low copy number alterations (copy-number low)
tumors with molecular alterations typical of endometrioid endometrial carcinomas
(five cases, 28%). Two of the latter cases, however, also had TP53 mutations and
higher number of alterations detected by FISH and could have progressed to a copy
number high phenotype. Most dedifferentiated carcinomas belonged to the
hypermutated group, whereas pure undifferentiated carcinomas shared molecular
genetic alterations with copy-number low or copy-number high tumors. These
results indicate that undifferentiated and dedifferentiated endometrial
carcinomas are molecularly heterogeneous tumors, which may have prognostic value.
PMID- 27491811
TI - Survival of buffalo bull spermatozoa: effect on structure and function due to
alpha-lipoic acid and cholesterol-loaded cyclodextrin.
AB - Sperm survival depending upon integral membranes and function is imperative for
fertilization. This study was designed to augment survival of buffalo spermatozoa
using alpha-lipoic acid (ALA) and cholesterol-loaded cyclodextrin (CLC) during
cryopreservation. Semen was frozen using 0, 0.5, 1, 1.5, 2 and 2.5 mmol L-1 ALA
(experiment 1) and ALA or CLC separately or together (experiment 2). Semen was
assessed for post-thaw motility, plasma membrane integrity (PMI), intact acrosome
and plasma membrane (IACR-IPM) and DNA integrity at 0, 1.5, 3 and 4.5 hr of
incubation. In experiment 1, use of 0.5 mmol L-1 ALA enhanced the sperm
cryosurvival and post-thaw longevity than other groups up to 4.5 hr of
incubation, and this concentration of ALA was used in second experiment with CLC.
The results revealed higher (p < .05) sperm survival function and time of sperm
attributes due to use of ALA than CLC and control. However, the sperm quality did
not improve (p > .05) when ALA was combined with CLC. In conclusion, survival of
buffalo bull spermatozoa during freeze-thawing and post-thaw incubation can be
enhanced more with ALA than CLC or control, followed by CLC than control.
However, there is no synergistic effect on survival of buffalo bull spermatozoa
due to ALA and CLC.
PMID- 27491812
TI - In Situ Calibration of a New Chemcatcher Configuration for the Determination of
Polar Organic Micropollutants in Wastewater Effluent.
AB - Passive sampling is proposed as an alternative to traditional grab- and composite
sampling modes. Investigated here is a novel passive sampler configuration, the
Chemcatcher containing an Atlantic HLB disk covered by a 0.2 MUm poly(ether
sulfone) membrane, for monitoring polar organic micropollutants (personal care
products, pharmaceuticals, and illicit drugs) in wastewater effluent. In situ
calibration showed linear uptake for the majority of detected micropollutants
over 9 days of deployment. Sampling rates (RS) were determined for 59 compounds
and were generally in the range of 0.01-0.10 L day(-1). The Chemcatcher was also
suitable for collecting chiral micropollutants and maintaining their enantiomeric
distribution during deployment. This is essential for their future use in
developing more accurate environmental risk assessments at the enantiomeric
level. Application of calibration data in a subsequent monitoring study showed
that the concentration estimated for 92% of micropollutants was within a factor
of 2 of the known concentration. However, their application in a legislative
context will require further understanding of the properties and mechanisms
controlling micropollutant uptake to improve the accuracy of reported
concentrations.
PMID- 27491813
TI - Fusarium and mycotoxin spectra in Swiss barley are affected by various cropping
techniques.
AB - Fusarium head blight is one of the most important cereal diseases worldwide.
Cereals differ in terms of the main occurring Fusarium species and the infection
is influenced by various factors, such as weather and cropping measures. Little
is known about Fusarium species in barley in Switzerland, hence harvest samples
from growers were collected in 2013 and 2014, along with information on
respective cropping factors. The incidence of different Fusarium species was
obtained by using a seed health test and mycotoxins were quantified by LC-MS/MS.
With these techniques, the most dominant species, F. graminearum, and the most
prominent mycotoxin, deoxynivalenol (DON), were identified. Between the three
main Swiss cropping systems, Organic, Extenso and Proof of ecological
performance, we observed differences with the lowest incidence and toxin
accumulation in organically cultivated barley. Hence, we hypothesise that this
finding was based on an array of growing techniques within a given cropping
system. We observed that barley samples from fields with maize as previous crop
had a substantially higher F. graminearum incidence and elevated DON accumulation
compared with other previous crops. Furthermore, the use of reduced tillage led
to a higher disease incidence and toxin content compared with samples from
ploughed fields. Further factors increasing Fusarium infection were high nitrogen
fertilisation as well as the application of fungicides and growth regulators.
Results from the current study can be used to develop optimised cropping systems
that reduce the risks of mycotoxin contamination.
PMID- 27491815
TI - Examining the interaction between cognitive control and reward sensitivity in
substance use dependence.
AB - BACKGROUND: Drug dependence is characterized by altered reward processing and
poor cognitive control, expressed as a preference for immediate rewards and
impaired inhibitory control, respectively. To examine the interaction between
reward processing (via the presence or absence of reward) and mechanisms of
inhibitory control in drug dependence, the current study used the Monetary
Incentive Control Task (MICT) to examine whether a group of opiate dependent
persons demonstrated greater difficulty exerting control over immediate rewards
compared to neutral stimuli. METHODS: The MICT is a Go/Stop paradigm that
examines inhibitory control over immediate rewards. Performance of 32 opiate
dependent individuals was compared to 29 healthy controls. RESULTS: Opiate users
demonstrated poorer inhibitory performance than controls, irrespective of cues
signaling immediate reward. Whereas control participants' responses were
modulated by probability cues, the opiate group did not show a capacity to up
regulate their cognitive control performance. CONCLUSIONS: The present results
suggest a general decrease in cognitive control in opiate dependence, accompanied
by a reduced ability to optimally modulate behavior in accordance with external
cues. Opiate users and controls did not differ in the interaction between
cognitive control and reward. The study highlights important issues for future
research to consider when further examining this interaction in drug dependence.
PMID- 27491816
TI - Prevalence of at-risk drinking among Brazilian truck drivers and its interference
on the performance of executive cognitive tasks.
AB - BACKGROUND: Binge drinking (BD) has been associated with an increase in the risk
of alcohol-related injuries. Alcohol continues to be the main substance consumed
by truck drivers, a population of special concern, since they are often involved
in traffic accidents. The aim of this study was to estimate the prevalence of BD
and its interference in the executive functioning among truck drivers in Sao
Paulo, Brazil. METHODS: A non-probabilistic sample of 684 truck drivers was
requested to answer a structured research instrument on their demographic data
and alcohol use. They performed cognitive tests to assess their executive
functioning and inventories about confounding variables. The participants were
then divided according to their involvement in BD. RESULTS: 17.5% of the
interviewees have reported being engaged in BD. Binge drinkers showed a better
performance on one test, despite having done so at the expense of more mistakes
and lower accuracy. More interestingly, binge drinkers took three seconds longer
than non-binge drinkers to inhibit an inadequate response, which is worrisome in
the context of traffic. Overall, the deleterious effect of BD on performance
remained after controlling for the effects of confounding variables in regression
logistic models. CONCLUSIONS: As the use of alcohol among truck drivers may be as
a way to get by with their work conditions, we believe that a negotiation between
their work organization and public authorities would reduce such use, preventing
negative interferences on truck drivers' cognitive functioning, which by its turn
may also prevent traffic accidents.
PMID- 27491814
TI - Vagal nerve stimulation improves mitochondrial dynamics via an M3
receptor/CaMKKbeta/AMPK pathway in isoproterenol-induced myocardial ischaemia.
AB - Mitochondrial dynamics-fission and fusion-are associated with ischaemic heart
disease (IHD). This study explored the protective effect of vagal nerve
stimulation (VNS) against isoproterenol (ISO)-induced myocardial ischaemia in a
rat model and tested whether VNS plays a role in preventing disorders of
mitochondrial dynamics and function. Isoproterenol not only caused cardiac injury
but also increased the expression of mitochondrial fission proteins [dynamin
related peptide1 (Drp1) and mitochondrial fission protein1 (Fis-1)) and decreased
the expression of fusion proteins (optic atrophy-1 (OPA1) and mitofusins1/2
(Mfn1/2)], thereby disrupting mitochondrial dynamics and leading to increase in
mitochondrial fragments. Interestingly, VNS restored mitochondrial dynamics
through regulation of Drp1, Fis-1, OPA1 and Mfn1/2; enhanced ATP content and
mitochondrial membrane potential; reduced mitochondrial permeability transition
pore (MPTP) opening; and improved mitochondrial ultrastructure and size.
Furthermore, VNS reduced the size of the myocardial infarction and ameliorated
cardiomyocyte apoptosis and cardiac dysfunction induced by ISO. Moreover, VNS
activated AMP-activated protein kinase (AMPK), which was accompanied by
phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinase beta
(CaMKKbeta) during myocardial ischaemia. Treatment with subtype-3 of muscarinic
acetylcholine receptor (M3 R) antagonist 4-diphenylacetoxy-N-methylpiperidine
methiodide or AMPK inhibitor Compound C abolished the protective effects of VNS
on mitochondrial dynamics and function, suggesting that M3 R/CaMKKbeta/AMPK
signalling are involved in mediating beneficial effects of VNS. This study
demonstrates that VNS modulates mitochondrial dynamics and improves mitochondrial
function, possibly through the M3 R/CaMKKbeta/AMPK pathway, to attenuate ISO
induced cardiac damage in rats. Targeting mitochondrial dynamics may provide a
novel therapeutic strategy in IHD.
PMID- 27491818
TI - In a tertiary maternity hospital, when should a paediatrician be present in the
delivery room?
AB - OBJECTIVE: 10% of newborns require positive pressure ventilation (PPV) at birth.
There are few data on prenatal or early postnatal factors that are predictive of
the need for a paediatrician in the delivery room. The study analysed prenatal
obstetric and early postnatal factors associated with the requirement for
paediatrician assistance in this setting. METHODS: Over a three-month period, all
consecutive births in a tertiary hospital's maternity unit were prospectively
evaluated with regard to the need for paediatrician assistance (requested either
before or after the delivery), the requirement for resuscitation, and transfer to
a neonatal intensive care unit (NICU). RESULTS: For a total of 584 consecutive
births, paediatrician assistance was requested before delivery in 170 cases
(30.5%) and after in 78 cases (13.3%). 78% of the newborns requiring PPV, 95.8%
of those requiring endotracheal intubation and 86.3% of those requiring transfer
to the NICU matched recently published prenatal criteria for paediatrician
assistance. Along with a low Apgar score and a cord blood pH <7.20, these
criteria covered 95% of the prenatal and early postnatal requests for
paediatrician assistance. CONCLUSIONS: These criteria for neonatal resuscitation
in the delivery room would enable medical staff to anticipate the need for
paediatrician assistance.
PMID- 27491817
TI - Age, period, and cohort effects in synthetic cannabinoid use among US
adolescents, 2011-2015.
AB - BACKGROUND: Synthetic cannabinoids use has been a public health concern given
association with hospitalization and death among users. While national reports
estimate that reported use is declining among adolescents, differences by birth
cohort may indicate subgroups who remain at higher risk, both in the overall
adolescent population and among demographic subgroups. METHODS: We estimated age,
period, and cohort models of self-reported past-year synthetic cannabinoid use
(queried as "synthetic marijuana" ["K2," "Spice"]) among 54,865 adolescents aged
13-19 attending high school from 2011 to 2015. RESULTS: Past-year use decreased
from 11.86% in 2011 to 4.75% in 2015. This decrease was best represented as a
linear downward trend. When stratified by key covariates, however, results
indicated evidence of a positive cohort effect for students of higher
socioeconomic status (SES). For those students, use did not decrease at the same
rate as the overall population; younger cohorts of high SES students remain at
higher risk for synthetic cannabinoid use than older cohorts as well as lower SES
peers. A similar and stronger association was found for frequent marijuana users
(>=20 occasions of past-year use). Multi-level models indicated that groups at
highest risk included older adolescents, Hispanics and other/mixed race students,
cigarette users, and frequent marijuana users. CONCLUSION: Synthetic cannabinoid
use is associated with morbidity as well as mortality; continued attention to
reducing synthetic cannabinoid use remains an important public health priority to
maximizing student health.
PMID- 27491819
TI - Development of a Web-based GIS monitoring and environmental assessment system for
the Black Sea: application in the Danube Delta area.
AB - In this paper, the development of a Web-based GIS system for the monitoring and
assessment of the Black Sea is presented. The integrated multilevel system is
based on the combination of terrestrial and satellite Earth observation data
through the technological assets provided by innovative information tools and
facilities. The key component of the system is a unified, easy to update
geodatabase including a wide range of appropriately selected environmental
parameters. The collection procedure of current and historical data along with
the methods employed for their processing in three test areas of the current
study are extensively discussed, and special attention is given to the overall
design and structure of the developed geodatabase. Furthermore, the information
system includes a decision support component (DSC) which allows assessment and
effective management of a wide range of heterogeneous data and environmental
parameters within an appropriately designed and well-tested methodology. The DSC
provides simplified and straightforward results based on a classification
procedure, thus contributing to a monitoring system not only for experts but for
auxiliary staff as well. The examples of the system's functionality that are
presented highlight its usability as well as the assistance that is provided to
the decision maker. The given examples emphasize on the Danube Delta area;
however, the information layers of the integrated system can be expanded in the
future to cover other regions, thus contributing to the development of an
environmental monitoring system for the entire Black Sea.
PMID- 27491821
TI - Cobalt-catalyzed C-H olefination of aromatics with unactivated alkenes.
AB - A cobalt-catalyzed C-H olefination of aromatic and heteroaromatic amides with
unactivated alkenes, allyl acetates and allyl alcohols is described. This method
offers an efficient route for the synthesis of vinyl and allyl benzamides in a
highly stereoselective manner. It is observed that the ortho substituent on the
benzamide moiety is crucial for the observation of allylated products in
unactivated alkenes.
PMID- 27491820
TI - Annexin A4-nuclear factor-kappaB feedback circuit regulates cell malignant
behavior and tumor growth in gallbladder cancer.
AB - Gallbladder cancer (GBC) is the most common malignant tumor of the biliary
system. However, the mechanisms underlying its tumor initiation, progression, and
metastasis are not yet fully understood. The annexin A4 (ANXA4) gene is highly
expressed in GBC tissues and may play an important role in the initiation and
progression of this disease. In this study, we examined the up-regulation of
ANXA4 in human GBC tissues and cell lines. Elevated ANXA4 correlated well with
invasion depth in GBC patients and predicted a poor prognosis. In vitro, GBC-SD
and NOZ cells with ANXA4 knockdown demonstrated increased apoptosis and inhibited
cell growth, migration, and invasion. Interactions between ANXA4 and nuclear
factor-kappaB (NF-kappaB) p65 proteins were detected. In vivo, ANXA4 knockdown
inhibited tumor growth of GBC cells in nude mice and down-regulated the
expression of downstream factors in the NF-kappaB signaling pathway. Taken
together, these data indicate that up-regulation of ANXA4 leads to activation of
the NF-kappaB pathway and its target genes in a feedback regulatory mechanism via
the p65 subunit, resulting in tumor growth in GBC.
PMID- 27491825
TI - Anatomy, histology and elemental profile of long bones and ribs of the Asian
elephant (Elephas maximus).
AB - This study evaluated the morphology and elemental composition of Asian elephant
(Elephas maximus) bones (humerus, radius, ulna, femur, tibia, fibula and rib).
Computerized tomography was used to image the intraosseous structure, compact
bones were processed using histological techniques, and elemental profiling of
compact bone was conducted using X-ray fluorescence. There was no clear evidence
of an open marrow cavity in any of the bones; rather, dense trabecular bone was
found in the bone interior. Compact bone contained double osteons in the radius,
tibia and fibula. The osteon structure was comparatively large and similar in all
bones, although the lacuna area was greater (P < 0.05) in the femur and ulna.
Another finding was that nutrient foramina were clearly present in the humerus,
ulna, femur, tibia and rib. Twenty elements were identified in elephant compact
bone. Of these, ten differed significantly across the seven bones: Ca, Ti, V, Mn,
Fe, Zr, Ag, Cd, Sn and Sb. Of particular interest was the finding of a
significantly larger proportion of Fe in the humerus, radius, fibula and ribs,
all bones without an open medullary cavity, which is traditionally associated
with bone marrow for blood cell production. In conclusion, elephant bones present
special characteristics, some of which may be important to hematopoiesis and bone
strength for supporting a heavy body weight.
PMID- 27491824
TI - Partying Last Weekend: Factors Related to Heavy Episodic Drinking Among People
Who Use Recreational Drugs.
AB - BACKGROUND: Heavy episodic drinking (HED) has negative consequences for both the
individual and society. Research on HED has focused mainly on the general
population while research into HED and other drug use among recreational drug
using populations is less developed. OBJECTIVES: This study explores factors
related to HED on a previous weekend among male and female recreational drug
users. METHODS: Cross-sectional interviews were undertaken with those age 19+ who
regularly use recreational drugs in a nightlife setting in two cities in Canada
(n = 931) between 2008 and 2014. Participants were asked about their alcohol and
other drug use the previous Friday or Saturday. Chi-square bivariate tests were
used to determine factors significantly associated with HED with significant
variables then entered into multivariate logistic regression models to determine
related factors for men and women. RESULTS: Results showed that 53.4% of all
participants met criteria for HED the previous weekend and the majority of those
had used at least one other drug. Multivariate models showed being in
postsecondary full-time, being between 19 and 25, using cocaine and using tobacco
the previous weekend was associated with HED for men. For women, using cocaine
the previous weekend was associated with HED, while being 26 and over, married or
common law and using marijuana was associated with lower odds of HED. CONCLUSION:
HED is common among recreational drug users but different factors were associated
HED for men and women. Interventions for recreational drug users should include
both alcohol and other drug messaging and be gender specific.
PMID- 27491822
TI - Introduction of a prognostic biomarker to strengthen risk stratification of
acutely admitted patients: rationale and design of the TRIAGE III cluster
randomized interventional trial.
AB - BACKGROUND: Several biomarkers have shown to carry prognostic value beyond
current triage algorithms and may aid in initial risk stratification of patients
in the emergency department (ED). It has yet to be established if information
provided by biomarkers can be used to prevent serious complications or deaths.
Our aim is to determine whether measurement of the blood level of the biomarker
soluble urokinase plasminogen activator receptor (suPAR) can enhance early risk
stratification leading to reduced mortality, lower rate of complications, and
improved patient flow in acutely admitted adult patients at the ED. The main
hypothesis is that the availability of suPAR can reduce all-cause mortality,
assessed at least 10 months after admission, by drawing attention towards
patients with an unrecognized high risk, leading to improved diagnostics and
treatment. METHODS: The study is designed as a cross-over cluster randomized
interventional trial. SuPAR is measured within 2 h after admission and
immediately reported to the treating physicians in the ED. All ED physicians are
educated in the prognostic capabilities of suPAR prior to the inclusion period.
The inclusion period began January 11(th) 2016 and ends June 6(th) 2016. The
study aims to include 10.000 patients in both the interventional and control arm.
The results will be presented in 2017. DISCUSSION: The present article aims to
describe the design and rationale of the TRIAGE III study that will investigate
whether the availability of prognostic information can improve outcome in acutely
admitted patients. This might have an impact on health care organization and
decision-making. TRIAL REGISTRATION: The trial is registered at
clinicaltrials.gov (ID NCT02643459 , November 13, 2015) and at the Danish Data
Protection agency (ID HGH-2015-042 I-Suite no. 04087).
PMID- 27491827
TI - Reference values and repeatability of the Schirmer tear tests I and II in
domesticated, clinically normal dromedary camels (Camelus dromedarius).
AB - OBJECTIVE: To determine the normal values and repeatability for Schirmer tear
test (STT) in clinically normal dromedary camels and to analyze the influence of
the age and gender on these values. ANIMALS STUDIED: Thirty clinically normal
dromedary camels of different ages (calves, immature, and mature). PROCEDURES:
Schirmer tear tests I and II were performed using commercial STT strips. Three
measurements were obtained from each eye over three consecutive weeks, and the
variance of these measurements was determined. RESULTS: Mean values and
coefficient of variation of STT I and STT II for the right and left eyes varied
significantly among camel groups (P < 0.05). For STT I, the most frequently
recorded values were >14-18, > 22-26, and >30-34 mm/min in calves, immature
camels, and mature camels, respectively. For STT II, however, the most frequently
recorded values were 7-14, >10-18, and >26-30 mm/min, respectively. The
interassay coefficients of variation were 1.7-14.4% and were significantly lower
in mature camels than in calves and immature camels (P < 0.05). Age was
positively correlated with STT I (r = 0.81) and STT II values (r = 0.88). No
significant variations were found between genders. CONCLUSIONS: This preliminary
study reports STT I and II values and repeatability in normal dromedary camels.
This information may assist veterinary practitioners in complete ophthalmic
examinations and in accurate diagnosis of ocular surface diseases affecting the
tear film in this species.
PMID- 27491826
TI - Simultaneous targeted activation of Notch1 and Vhl-disruption in the kidney
proximal epithelial tubular cells in mice.
AB - Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney
cancer, representing approximately 75% of all renal neoplasms. ccRCC is known to
be strongly associated with silencing of the von Hippel Lindau (VHL) tumor
suppressor gene, yet VHL deficiency alone does not seem to be sufficient to drive
the oncogenic transformation of normal renal epithelium and induce renal
tumorigenesis. We, and others, have previously suggested that constitutive
activation of the Notch signaling pathway, alongside with VHL loss, contribute to
the oncogenic features of ccRCC. Here we report a prevailing hyperactivation of
the Notch1 receptor in human ccRCC relative to the healthy counterpart. To
explore the consequences of the elevated Notch1 signaling observed in ccRCC
patient material, we made use of a conditional mouse model based on concurrent
ectopic expression of constitutively active Notch1 (NICD1) and deletion of the
Vhl gene. Histological examination of the kidneys of the conditional mice
demonstrate the existence of nests of dysplastic cells with a clear cytoplasm as
a consequence of lipid accumulation, thus displaying a one important hallmark of
human ccRCC.
PMID- 27491828
TI - HIV-1 Tat exacerbates lipopolysaccharide-induced cytokine release via TLR4
signaling in the enteric nervous system.
AB - The loss of gut epithelium integrity leads to translocation of microbes and
microbial products resulting in immune activation and drives systemic
inflammation in acquired immunodeficiency syndrome (AIDS) patients. Although
viral loads in HIV patients are significantly reduced in the post-cART era,
inflammation and immune activation persist and can lead to morbidity. Here, we
determined the interactive effects of the viral protein HIV-1 Tat and
lipopolysaccharide (LPS) on enteric neurons and glia. Bacterial translocation was
significantly enhanced in Tat-expressing (Tat+) mice. Exposure to HIV-1 Tat in
combination with LPS enhanced the expression and release of the pro-inflammatory
cytokines IL-6, IL-1beta and TNF-alpha in the ilea of Tat+ mice and by enteric
glia. This coincided with enhanced NF-kappaB activation in enteric glia that was
abrogated in glia from TLR4 knockout mice and by knockdown (siRNA) of MyD88 siRNA
in wild type glia. The synergistic effects of Tat and LPS resulted in a reduced
rate of colonic propulsion in Tat+ mice treated with LPS. These results show that
HIV-1 Tat interacts with the TLR4 receptor to enhance the pro-inflammatory
effects of LPS leading to gastrointestinal dysmotility and enhanced immune
activation.
PMID- 27491829
TI - Effects of multiple types of stigma on the probability of HIV disclosure to sex
partners: a systematic review.
AB - Previous review studies explored factors related to the process of HIV
disclosure. However, none of these review studies specifically focused on the
effects of stigma on HIV disclosure to sex partners. A comprehensive systematic
review of empirical studies on the effects of stigma on HIV disclosure to sex
partners was conducted until December 2014. Twenty-seven articles published in
English-language journals were selected, and study characteristics and findings
were evaluated. Inconsistent findings in the assessment of impacts of stigma on
HIV disclosure to sex partners were documented. Three underlying plausible
reasons were identified, and these included: (1) different types of stigma may
have different effects on HIV disclosure to sex partners; (2) studies used
different measurement strategies; and (3) varied personal backgrounds and health
factors that can mitigate, facilitate or moderate the effect of stigma on HIV
disclosure to sex partners. Studies with precise definition measurements of
specific types of stigma used them appropriately in a matching context to provide
more consistent research results. This review identifies the need for further
investigation into how the HIV disclosure process is shaped by particular types
of stigma, types of sex partners and demographic characteristics of people living
with HIV/AIDS.
PMID- 27491831
TI - Evaluation of a novel strategy of triage in the haematology ambulatory care
setting.
AB - BACKGROUND: In 2010, wait-times for new patients referred to see a haematologist
at our outpatient tertiary care centre clinic exceeded 6 months. The provision of
written recommendations for a subset of referred patients was undertaken to
reduce patient wait-times. These recommendation letters outlined possible causes
of the abnormality for which the patient was being referred and suggested a
course of action for follow-up, and patients were then managed by their referring
practitioner. We sought to characterize the cohort of patients for whom written
recommendations were written and assess whether written recommendations were a
satisfactory alternative for the referring practitioner. METHODS: All haematology
patient referrals managed with written recommendations in 2010 were included in
the study and were assessed one year later. Referring practitioners who received
written recommendations were sent a short survey to evaluate their satisfaction
with this process. RESULTS: A total of 444 of 2400 referrals were managed with a
letter. At 1-year follow-up, 58 (13%, 95% CI) of the abnormalities which prompted
the referral had resolved and 201 (45%, 95%CI) had remained stable. There was a
single haematology-related death during the 1-year follow-up and the
haematological abnormality worsened in 4 (1%) patients. Of 203 (71%) referring
practitioners who responded to the satisfaction survey, 90% (95% CI) indicated
that they would be satisfied with written recommendations in the future.
INTERPRETATION: The provision of written recommendations appears to be a safe and
satisfactory alternative to an inperson outpatient assessment in certain well
defined subsets of stable outpatients with haematologic abnormalities.
PMID- 27491832
TI - BMI as a Predictor of Spinal Cord Stimulation Success in Chronic Pain Patients.
AB - BACKGROUND: Spinal cord stimulation (SCS) is an effective method of treating
chronic pain. Obese patients are overrepresented in chronic pain cases. We
examine the effect of body mass index (BMI) on SCS success. METHODS: We
prospectively follow outcome measures including visual analog score, Beck
Depression Inventory (BDI), McGill Pain Questionnaire, Oswestry Disability Index
(ODI), Pain Catastrophizing Scale (PCS), and the Insomnia Severity Index at
baseline, six months, and one year postoperatively. Retrospectively, we examined
whether our patients with a BMI above the 75th percentile (BMI >=36.5) had worse
outcomes. RESULTS: Our analysis included thoracic and cervical SCS patients-19
with a BMI >=36.5 and 58 with a BMI <36.5. High BMI patients experienced less BDI
improvement at 6 months (T(df) 2.257(36); p = 0.030; 95% CI [4.7%, 87.4%]) and
one year (2.74(28); p = 0.011; 95% CI [18.1%, 125.0%]) post-SCS. High BMI
patients had less improvement in pain as measured by the PCS at one year (U =
79.5; p = 0.045; 95% CI [-116.0%, 0.0%]). DISCUSSION: Each group experienced
successful surgical outcomes. High BMI patients had less BDI improvement at six
months and one year and less PCS improvement at one year. These data aid us in
counseling our patients preoperatively.
PMID- 27491830
TI - Diabetes and Cognitive Impairment.
AB - Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with
reduced performance on multiple domains of cognitive function and with evidence
of abnormal structural and functional brain magnetic resonance imaging (MRI).
Cognitive deficits may occur at the very earliest stages of diabetes and are
further exacerbated by the metabolic syndrome. The duration of diabetes and
glycemic control may have an impact on the type and severity of cognitive
impairment, but as yet we cannot predict who is at greatest risk of developing
cognitive impairment. The pathophysiology of cognitive impairment is
multifactorial, although dysfunction in each interconnecting pathway ultimately
leads to discordance in metabolic signaling. The pathophysiology includes defects
in insulin signaling, autonomic function, neuroinflammatory pathways,
mitochondrial (Mt) metabolism, the sirtuin-peroxisome proliferator-activated
receptor-gamma co-activator 1alpha (SIRT-PGC-1alpha) axis, and Tau signaling.
Several promising therapies have been identified in pre-clinical studies, but
remain to be validated in clinical trials.
PMID- 27491834
TI - Reductive exfoliation of substoichiometric MoS2 bilayers using hydrazine salts.
AB - Substoichiometric molybdenum disulphide (MoSx) nanosheets are successfully
synthesised following a novel reductive route using hydrazine salts. The
resulting two dimensional crystals are found to be highly monodispersed in
thickness, forming exclusively 1.9 +/- 0.2 nm thick bilayers. The lateral
dimensions of the nanosheets are governed by the precursor bulk particle's size.
Exploring a range of hydrazine derivatives with various degrees of steric
hindrance leads to the conclusion that intercalation does not occur during the
process and that exfoliation is instead facilitated by the reduction of Mo
centres leading to the exfoliation of substoichiometric bilayers with distorted
lattices. The lattice distortion is found to be persistent across all samples
with XPS analysis pointing towards a S to Mo ratio of 1.2. The resulting material
features an electronic bandgap of 2.1 eV, which is wider than that of pristine
monolayer MoS2 with relatively longer radiative decay time.
PMID- 27491833
TI - ANGPTL2 is associated with an increased risk of cardiovascular events and death
in diabetic patients.
AB - AIMS/HYPOTHESIS: A high serum angiopoietin-like 2 (ANGPTL2) concentration is an
independent risk factor for developing diabetes and is associated with insulin
resistance and atherosclerosis. In this work, we have examined the impact of
serum ANGPTL2 on improving cardiovascular (CV) risk stratification in patients
with type 2 diabetes. METHODS: A prospective, monocentric cohort of consecutive
type 2 diabetes patients (the SURDIAGENE cohort; total of 1353 type 2 diabetes
patients; 58% men, mean +/- SD age 64 +/- 11 years) was followed for a median of
6.0 years for death as primary endpoint and major adverse CV events (MACE; i.e.
CV death, myocardial infarction or stroke) as a secondary endpoint. Patients with
end-stage renal disease, defined as a requirement for dialysis or a history of
kidney transplantation, were excluded. Patients were grouped into quartiles
according to ANGPTL2 concentrations at inclusion: <11.2 (Q1), 11.2-14.7 (Q2),
14.8-19.5 (Q3) or >19.5 (Q4) ng/ml. RESULTS: During follow up, 367 patients
(representing 4.5% of the total person-years) died and 290 patients (representing
3.7% of the total person-years) presented with MACE. Both the survival and MACE
free survival rates were significantly different between ANGPTL2 quartiles
(logrank 82.12, p < 0.0001 for death; and logrank 65.14, p < 0.0001 for MACE).
Patients with ANGPTL2 concentrations higher than 19.5 ng/ml (Q4) had a
significantly higher risk of death and MACE than those with ANGPTL2 levels of
19.5 ng/ml or less (Q1-3) (HR for death 2.44 [95% CI 1.98, 3.00], p < 0.0001; HR
for MACE 2.43 [95% CI 1.92, 3.06], p < 0.0001) after adjustment for sex, age and
established CV risk factors. Using ANGPTL2 concentrations, prediction of the risk
of mortality, as assessed by integrated discrimination improvement (IDI), was
significantly improved (IDI 0.006 +/- 0.002, p = 0.0002).
CONCLUSIONS/INTERPRETATION: In patients with type 2 diabetes, serum ANGPTL2
concentrations were independently associated with death and MACE. Therefore,
ANGPTL2 is a promising candidate biomarker for improving risk stratification in
type 2 diabetes patients, and may prove to be a valuable therapeutic target.
PMID- 27491835
TI - Variations in pelvic lymph node dissection in invasive bladder cancer: A Dutch
nationwide population-based study during centralization of care.
AB - OBJECTIVES: To assess temporal trends in radical cystectomy (RC) and pelvic lymph
node dissection (PLND) and the effect of centralization of care in the
Netherlands between 2006 and 2012. PATIENTS AND METHODS: This nationwide
population-based study included 3524 patients from the Netherlands Cancer
Registry who underwent RC as the primary treatment for cT1-4a, N0 or Nx, M0
urothelial carcinoma. Annual application rates of PLND, median LNC, and rates of
node-positive disease (pN+) were compared by linear-by-linear association.
Multivariable logistic regression was performed to identify patients' and
hospital characteristics associated with PLND and LNC>=10, and to study
associations between LNC and pN+disease. RESULTS: In total, 3,191 (91%) patients
had PLND during RC and the use increased from 84% in 2006 to 96% in 2012
(P<0.001). Owing to centralization of care in 2010 (at least 10RCs/y/hospital),
significantly more patients were treated in high-volume hospitals (>=20RC per
year) in 2011 and 2012. PLND use was highest in males, younger patients and in
academic, teaching, and high-volume hospitals (>=20RC per year). In 2012, PLND
application rates were comparable for academic, teaching, and nonteaching
hospitals (P = 0.344). Median LNC increased from 7 in 2006 to 13 in 2012
(P<0.001), 55% had an LNC>=10 (63% in 2012). Furthermore, lymph node count
(LNC)>=10 was associated with cT3-4a and, pN+disease, R0 and treatment in
academic, teaching, or high-volume hospitals (>=20RC per year). Rate of
pN+disease increased from 18% to 24% between 2006 and 2012 (P = 0.014). This
trend was significantly associated with increased LNC on a continuous scale (odds
ratio = 1.03). CONCLUSIONS: After centralization of care, PLND during RC for cT1
4a, N0 or Nx, M0 urothelial carcinoma has become standard in all types of Dutch
hospitals. The increase in LNC between 2006 and 2012 was associated with a higher
incidence of pN+disease and suggests more adequate template extension and
adherence to contemporary guidelines in recent years.
PMID- 27491837
TI - Dynamic Predictive Scores for Cardiac Surgery-Associated Acute Kidney Injury.
AB - BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common
complication with a poor prognosis. In order to identify modifiable perioperative
risk factors for AKI, which existing risk scores are insufficient to predict, a
dynamic clinical risk score to allow clinicians to estimate the risk of CSA-AKI
from preoperative to early postoperative periods is needed. METHODS AND RESULTS:
A total of 7233 cardiac surgery patients in our institution from January 2010 to
April 2013 were enrolled prospectively and distributed into 2 cohorts. Among the
derivation cohort, logistic regression was used to analyze CSA-AKI risk factors
preoperatively, on the day of ICU admittance and 24 hours after ICU admittance.
Sex, age, valve surgery combined with coronary artery bypass grafting,
preoperative NYHA score >2, previous cardiac surgery, preoperative kidney
(without renal replacement therapy) disease, intraoperative cardiopulmonary
bypass application, intraoperative erythrocyte transfusions, and postoperative
low cardiac output syndrome were identified to be associated with CSA-AKI. Among
the other 1152 patients who served as a validation cohort, the point scoring of
risk factor combinations led to area under receiver operator characteristics
curves (AUROC) values for CSA-AKI prediction of 0.74 (preoperative), 0.75 (on the
day of ICU admission), and 0.82 (postoperative), and Hosmer-Lemeshow goodness-of
fit tests revealed a good agreement of expected and observed CSA-AKI rates.
CONCLUSIONS: The first dynamic predictive score system, with Kidney Disease:
Improving Global Outcomes (KDIGO) AKI definition, was developed and predictive
efficiency for CSA-AKI was validated in cardiac surgery patients.
PMID- 27491836
TI - Diagnosis and Management of Cardiovascular Disease in Advanced and End-Stage
Renal Disease.
PMID- 27491838
TI - Air pollution affects lung cancer survival.
PMID- 27491839
TI - Air pollution affects lung cancer survival.
AB - RATIONALE: Exposure to ambient air pollutants has been associated with increased
lung cancer incidence and mortality, but due to the high case fatality rate,
little is known about the impacts of air pollution exposures on survival after
diagnosis. This study aimed to determine whether ambient air pollutant exposures
are associated with the survival of patients with lung cancer. METHODS:
Participants were 352 053 patients with newly diagnosed lung cancer during 1988
2009 in California, ascertained by the California Cancer Registry. Average
residential ambient air pollutant concentrations were estimated for each
participant's follow-up period. Cox proportional hazards models were used to
estimate HRs relating air pollutant exposures to all-cause mortality overall and
stratified by stage (localised only, regional and distant site) and histology
(squamous cell carcinoma, adenocarcinoma, small cell carcinoma, large cell
carcinoma and others) at diagnosis, adjusting for potential individual and area
level confounders. RESULTS: Adjusting for histology and other potential
confounders, the HRs associated with 1 SD increases in NO2, O3, PM10, PM2.5 for
patients with localised stage at diagnosis were 1.30 (95% CI 1.28 to 1.32), 1.04
(95% CI 1.02 to 1.05), 1.26 (95% CI 1.25 to 1.28) and 1.38 (95% CI 1.35 to 1.41),
respectively. Adjusted HRs were smaller in later stages and varied by
histological type within stage (p<0.01, except O3). The largest associations were
for patients with early-stage non-small cell cancers, particularly
adenocarcinomas. CONCLUSIONS: These epidemiological findings support the
hypothesis that air pollution exposures after lung cancer diagnosis shorten
survival. Future studies should evaluate the impacts of exposure reduction.
PMID- 27491840
TI - LOCAL HEALTH TECHNOLOGY ASSESSMENT IN CANADA: CURRENT STATE AND NEXT STEPS.
AB - OBJECTIVES: Canada has witnessed expansion of the health technology assessment
(HTA) infrastructure in the last 25 years. Local HTA entities at the hospital or
regional level are emerging to assist decision makers in the acquisition,
implementation, maintenance, and disinvestment of healthcare technologies. There
is a need to facilitate collaboration and exchange of expertise and knowledge
between these entities regarding the role of local HTA in Canada. METHODS: In
November 2013, the pan-Canadian Collaborative hosted a symposium,
Hospital/Regional HTA: Local Evidence-based Decisions for Health Care
Sustainability, bringing together over 60 HTA producers, researchers,
stakeholders, and manufacturers involved in local HTA across Canada. The
objective was to showcase the diversity of local HTA in Canada, while
highlighting common gaps to be addressed. RESULTS: The Symposium focused on
current practices in local HTA in Canada to support informed decision making, and
opportunities for information sharing and provide equal access to timely evidence
based information to decision makers. The main themes included assessment of
evidence for local HTA, contextualization, stakeholder engagement in local HTA,
knowledge translation and impact of recommendations, and challenges and
opportunities for local HTA. CONCLUSIONS: Local HTA in Canada complements HTAs
conducted at the provincial and federal levels to improve the efficient and
effective health service delivery in institutions or regions faced with limited
resources. Some challenges faced by local HTA producers to influence hospital
policies and clinical practice involve the engagement of healthcare professionals
and potential lack of training and support necessary for the introduction of a
new technology.
PMID- 27491841
TI - Identification of survival-promoting OSIP108 peptide variants and their
internalization in human cells.
AB - The plant-derived decapeptide OSIP108 increases tolerance of yeast and human
cells to apoptosis-inducing agents, such as copper and cisplatin. We performed a
whole amino acid scan of OSIP108 and conducted structure-activity relationship
studies on the induction of cisplatin tolerance (CT) in yeast. The use of
cisplatin as apoptosis-inducing trigger in this study should be considered as a
tool to better understand the survival-promoting nature of OSIP108 and not for
purposes related to anti-cancer treatment. We found that charged residues (Arg,
His, Lys, Glu or Asp) or a Pro on positions 4-7 improved OSIP108 activity by 10%
or more. The variant OSIP108[G7P] induced the most pronounced tolerance to toxic
concentrations of copper and cisplatin in yeast and/or HepG2 cells. Both OSIP108
and OSIP108[G7P] were shown to internalize equally into HeLa cells, but at a
higher rate than the inactive OSIP108[E10A], suggesting that the peptides can
internalize into cells and that OSIP108 activity is dependent on subsequent
intracellular interactions. In conclusion, our studies demonstrated that
tolerance/survival-promoting properties of OSIP108 can be significantly improved
by single amino acid substitutions, and that these properties are dependent on
(an) intracellular target(s), yet to be determined.
PMID- 27491842
TI - Advances in LC: bioanalytical method transfer.
AB - There are three main reasons for transferring from an existing bioanalytical
assay to an alternative chromatographic method: speed, cost and sensitivity.
These represent a challenge to the analyst in that there is an interplay between
these three considerations and one factor is often improved at the expense of
another. These three factors act as drivers to encourage technology development
and support its uptake. The more recently introduced chromatographic technologies
may show significant improvements against one of more of these factors relative
to conventional 4.6-mm id reversed-phase HPLC. In this article, some of these new
chromatographic approaches will be considered in terms of what they can offer the
bioanalysts.
PMID- 27491843
TI - A simple, effective approach for rapid development of high-throughput and
reliable LC-MS/MS bioanalytical assays.
AB - BACKGROUND: Rapidly developing LC-MS/MS assays with high-throughput and quality
are challenging yet desired. Methodology & results: A simple method development
approach was reported and demonstrated with the quantitative bioanalysis of BMS
984478, a hepatitis C virus nonstructural protein 5A inhibitor. An accurate,
precise and robust LC-MS/MS method for the quantitation of BMS-984478 in rat and
monkey plasma was developed and validated. Incurred sample reanalysis evaluation
passed with 100% of samples meeting the acceptance criteria. The validated assay
was successfully applied in toxicology studies without any failed runs.
CONCLUSION: The approach was successfully applied to the bioanalysis of BMS
984478 in toxicology and clinical studies. This approach was shown to be
effective and reliable in speeding the development of high-throughput and
reliable LC-MS/MS assays.
PMID- 27491844
TI - Running ahead of doping: analytical advances and challenges faced by modern
laboratories ahead of Rio 2016.
PMID- 27491845
TI - Determination of urinary aldosterone using a plasma aldosterone 2D ID LC-MS/MS
method.
AB - AIM: In the diagnosis for primary aldosteronism, the measurement of urinary
aldosterone is part of the confirmation test but diagnostic accuracy may be
blunted due to poor immunoassay performance for urinary aldosterone. Nowadays,
plasma aldosterone concentrations are measured preferably by LC-MS/MS yet such
methods for urinary aldosterone are lacking. METHODS & RESULTS: We show that
plasma and urinary aldosterone can be measured with the same 2D isotope dilution
LC-MS/MS method. The accuracy of the method was tested against a certified
reference material. The reference values for plasma and urinary aldosterone were
established. DISCUSSION & CONCLUSION: With this method, urinary aldosterone
concentrations can be measured precisely, simply and accurately together with
plasma samples with one set of calibration standards.
PMID- 27491846
TI - LC-MS/MS assay of ropinirole in rat biological matrices: elimination of
lysoglycerophosphocholines-based matrix effect.
AB - AIM: To adequately support PK evaluation of ropinirole in rats following
intranasal administration, it was desirable to determine ropinirole
concentrations in rat plasma, brain homogenate and microdialysate. Results &
methodology: A robust LC-MS/MS method has been developed for the determination of
ropinirole in biological samples. Liquid-liquid extraction using ethyl acetate
eliminated matrix effect due to significantly reduced levels of
lysoglycerophosphocholines. The assay was fully validated with dynamic ranges of
0.01-20 ng/ml for plasma and brain homogenate samples and 0.1-200 ng/ml for
microdialysate samples. CONCLUSION: The proposed method was accurate and precise
for the quantification of ropinirole in biological samples and was successfully
applied to a microdialysis study of ropinirole in rats.
PMID- 27491847
TI - Case-based Learning Outperformed Simulation Exercises in Disaster Preparedness
Education Among Nursing Trainees in India: A Randomized Controlled Trial.
AB - OBJECTIVE: In resource-constrained environments, appropriately employing triage
in disaster situations is crucial. Although both case-based learning (CBL) and
simulation exercises (SEs) commonly are utilized in teaching disaster
preparedness to adult learners, there is no substantial evidence supporting one
as a more efficacious methodology. This randomized controlled trial (RCT)
evaluated the effectiveness of CBL versus SEs in addition to standard didactic
instruction in knowledge attainment pertaining to disaster triage preparedness.
METHODS: This RCT was performed during a one-day disaster preparedness course in
Lucknow, India during October 2014. Following provision of informed consent,
nursing trainees were randomized to knowledge assessment after didactic teaching
(control group); didactic plus CBL (Intervention Group 1); or didactic plus SE
(Intervention Group 2). The educational curriculum used the topical focus of
triage processes during disaster situations. Cases for the educational
intervention sessions were scripted, identical between modalities, and employed
structured debriefing. Trained live actors were used for SEs. After primary
assessment, the groups underwent crossover to take part in the alternative
educational modality and were re-assessed. Two standardized multiple-choice
question batteries, encompassing key core content, were used for assessments. A
sample size of 48 participants was calculated to detect a >=20% change in mean
knowledge score (alpha=0.05; power=80%). Robustness of randomization was
evaluated using X 2, anova, and t-tests. Mean knowledge attainment scores were
compared using one- and two-sample t-tests for intergroup and intragroup
analyses, respectively. RESULTS: Among 60 enrolled participants, 88.3% completed
follow-up. No significant differences in participant characteristics existed
between randomization arms. Mean baseline knowledge score in the control group
was 43.8% (standard deviation=11.0%). Case-based learning training resulted in a
significant increase in relative knowledge scores at 20.8% (P=0.003) and 10.3%
(P=.033) in intergroup and intragroup analyses, respectively. As compared to
control, SEs did not significantly alter knowledge attainment scores with an
average score increase of 6.6% (P=.396). In crossover intra-arm analysis, SEs
were found to result in a 26.0% decrement in mean assessment score (P < .001).
CONCLUSIONS: Among nursing trainees assessed in this RCT, the CBL modality was
superior to SEs in short-term disaster preparedness educational translation.
Simulation exercises resulted in no detectable improvement in knowledge
attainment in this population, suggesting that CBL may be utilized preferentially
for adult learners in similar disaster training settings. Aluisio AR , Daniel P ,
Grock A , Freedman J , Singh A , Papanagnou D , Arquilla B . Case-based learning
outperformed simulation exercises in disaster preparedness education among
nursing trainees in India: a randomized controlled trial. Prehosp Disaster Med.
2016;31(5):516-523.
PMID- 27491848
TI - Insight into the kinetics and thermodynamics of the hydride transfer reactions
between quinones and lumiflavin: a density functional theory study.
AB - The kinetics and equilibrium of the hydride transfer reaction between lumiflavin
and a number of substituted quinones was studied using density functional theory.
The impact of electron withdrawing/donating substituents on the redox potentials
of quinones was studied. In addition, the role of these substituents on the
kinetics of the hydride transfer reaction with lumiflavin was investigated in
detail under the transition state (TS) theory assumption. The hydride transfer
reactions were found to be more favorable for an electron-withdrawing
substituent. The activation barrier exhibited a quadratic relationship with the
driving force of these reactions as derived under the formalism of modified
Marcus theory. The present study found a significant extent of electron
delocalization in the TS that is stabilized by enhanced electrostatic,
polarization, and exchange interactions. Analysis of geometry, bond-orders, and
energetics revealed a predominant parallel (Leffler-Hammond) effect on the TS.
Closer scrutiny reveals that electron-withdrawing substituents, although located
on the acceptor ring, reduce the N-H bond order of the donor fragment in the
precursor complex. Carried out in the gas-phase, this is the first ever report of
a theoretical study of flavin's hydride transfer reactions with quinones,
providing an unfiltered view of the electronic effect on the nuclear
reorganization of donor-acceptor complexes.
PMID- 27491849
TI - Photoinduced hydrogen-bonding dynamics.
AB - Hydrogen bonding dynamics has received extensive research attention in recent
years due to the significant advances in femtolaser spectroscopy experiments and
quantum chemistry calculations. Usually, photoexcitation would cause changes in
the hydrogen bonding formed through the interaction between hydrogen donor and
acceptor molecules on their ground electronic states, and such transient
strengthening or weakening of hydrogen bonding could be crucial for the
photophysical transformations and the subsequent photochemical reactions that
occurred on a time scale from tens of femtosecond to a few nanoseconds. In this
article, we review the combined experimental and theoretical studies focusing on
the ultrafast electronic and vibrational hydrogen bonding dynamics. Through these
studies, new mechanisms and proposals and common rules have been put forward to
advance our understanding of the hydrogen bondings dynamics in a variety of
important photoinduced phenomena like photosynthesis, dual fluorescence emission,
rotational reorientation, excited-state proton transfer and charge transfer
processes, chemosensor fluorescence sensing, rearrangements of the hydrogen-bond
network including forming and breaking hydrogen bond in water. Graphical Abstract
We review the recent advances on exploring the photoinduced hydrogen bonding
dynamics in solutions through a joint approach of laser spectroscopy and
theoretical calculation. The reviewed studies have put forward a new mechanism,
new proposal, and new rule for a variety of photoinduced phenomena such as
photosynthesis, dual fluorescence emission, rotational reorientation, excited
state proton transfer and charge transfer, chemosensor fluorescence sensing, and
rearrangements of the hydrogen-bond network in water.
PMID- 27491850
TI - In-silico studies on DegP protein of Plasmodium falciparum in search of anti
malarials.
AB - Despite encouraging progress over the past decade, malaria caused by the
Plasmodium parasite continues to pose an enormous disease burden and is one of
the major global health problems. The extreme challenge in malaria management is
the resistance of parasites to traditional monochemotherapies like chloroquine
and sulfadoxine-pyrimethamine. No vaccine is yet in sight, and the foregoing
effective drugs are also losing ground against the disease due to the resistivity
of parasites. New antimalarials with novel mechanisms of action are needed to
circumvent existing or emerging drug resistance. DegP protein, secretory in
nature has been shown to be involved in regulation of thermo-oxidative stress
generated during asexual life cycle of Plasmodium, probably required for survival
of parasite in host. Considering the significance of protein, in this study, we
have generated a three-dimensional structure of PfDegP followed by validation of
the modeled structure using several tools like RAMPAGE, ERRAT, and others. We
also performed an in-silico screening of small molecule database against PfDegP
using Glide. Furthermore, molecular dynamics simulation of protein and protein
ligand complex was carried out using GROMACS. This study substantiated potential
drug-like molecules and provides the scope for development of novel antimalarial
drugs.
PMID- 27491851
TI - Evolution of the hydrogen-bonding motif in the melamine-cyanuric acid co-crystal:
a topological study.
AB - The melamine (M)/cyanuric acid (CA) supramolecular system is perhaps one of the
most exploited in the field of self-assembly because of the high complementarity
of the components. However, it is necessary to investigate further the factors
involved in the assembly process. In this study, we analyzed a set of 13 M n /CA
m clusters (with n , m = 1, 2, 3), taken from crystallographic data, to
characterize the nature of the hydrogen bonds involved in the self-assembly of
these components as well as to provide greater understanding of the phenomenon.
The calculations were performed at the B3LYP/6-311++G(d,p) and omega-B97XD
(single point) levels of theory, and the interactions were analyzed within the
framework of the quantum theory of atoms in molecules and by means of molecular
electrostatic potential maps. Our results show that the stablest structure is the
rosette-type motif and the aggregation mechanism is governed by a combination of
cooperative and anticooperative effects. Our topological results explain the
polymorphism in the self-assembly of coadsorbed monolayers of M and CA. Graphical
abstract The aggregation steps of the melamine-cyanuric co-crystal is driven by a
hydrogen-bonded network which is governed by a complex combination of cooperative
and anticooperative effects.
PMID- 27491852
TI - The dopamine D2 receptor dimer and its interaction with homobivalent antagonists:
homology modeling, docking and molecular dynamics.
AB - In order to apply structure-based drug design techniques to G protein-coupled
receptor complexes, it is essential to model their 3D structure and to identify
regions that are suitable for selective drug binding. For this purpose, we have
developed and tested a multi-component protocol to model the inactive
conformation of the dopamine D2 receptor dimer, suitable for interaction with
homobivalent antagonists. Our approach was based on protein-protein docking,
applying the Rosetta software to obtain populations of dimers as present in
membranes with all the main possible interfaces. Consensus scoring based on the
values and frequencies of best interfaces regarding four scoring parameters,
Rosetta interface score, interface area, free energy of binding and energy of
hydrogen bond interactions indicated that the best scored dimer model possesses a
TM4-TM5-TM7-TM1 interface, which is in agreement with experimental data. This
model was used to study interactions of the previously published dopamine D2
receptor homobivalent antagonists based on clozapine,1,4-disubstituted aromatic
piperidines/piperazines and arylamidoalkyl substituted phenylpiperazine
pharmacophores. It was found that the homobivalent antagonists stabilize the
receptor-inactive conformation by maintaining the ionic lock interaction, and
change the dimer interface by disrupting a set of hydrogen bonds and maintaining
water- and ligand-mediated hydrogen bonds in the extracellular and intracellular
part of the interface. Graphical Abstract Structure of the final model of the
dopamine D2 receptor homodimer, indicating the distancebetween Tyr37 and Tyr 5.42
in the apo form (left) and in the complex with the ligand (right).
PMID- 27491853
TI - H2 adsorption and dissociation on PdO(101) films supported on rutile TiO2 (110)
facet: elucidating the support effect by DFT calculations.
AB - To explore metal oxide-support interactions and their effect, H2 adsorption and
dissociation on PdO(101)/TiO2(110) films with different film thicknesses, in
comparison with that on pure PdO(101) surface without TiO2(110) support, were
studied by density functional theory calculation. A monolayer PdO(101) film
supported on TiO2 facet shows different properties to a pure PdO(101) surface. On
the monolayer PdO(101)/TiO2(110) film, TiO2 support leads to stronger molecular
adsorption of H2 on coordinatively unsaturated Pd top sites than that on a pure
PdO surface. H2 dissociation with the formation of OH was preferred
thermodynamically but slightly unfavorable kinetically on the monolayer PdO film
due to the TiO2 support effect. Graphical abstract On the monolayer
PdO(101)/TiO2(110) film, the TiO2 support effect leads to stronger H2 molecular
adsorption on coordinatively unsaturated Pd top sites than on pure PdO surface.
H2 dissociation with the formation of OH is preferred thermodynamically but
slightly unfavorable kinetically on the film due to the TiO2 support effect.
PMID- 27491854
TI - Fluorescein photodiagnosis of idiopathic retinal vasculitis, aneurysms, and
neuroretinitis (IRVAN) syndrome: A case report and long-term outcome of
photocoagulation therapy.
AB - Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome is
a disease characterized by multiple retinal macroaneurysms, neuroretinitis and
peripheral capillary non-perfusion, leading to irreversible visual loss. It
includes five stages and has previously been rarely reported. IRVAN syndrome is
especially rare in Asia. In this report, we describe laser diagnosis and therapy
in an Asian patient with IRVAN syndrome over two years of follow-up. We observed
non-perfusion retina and dilated retinal capillaries in the contralateral eye.
Photocoagulation is an effective therapy to control retinal macroaneurysms and
nonperfusions and to prevent visual loss, particularly in the early stages of
IRVAN syndrome (stages 2 & 3). To the best of our knowledge, this is the first
long-term observation of photocoagulation in IRVAN syndrome. We discovered the
early signs of such lesions, which may be beneficial for clinical diagnosis and
therapy.
PMID- 27491855
TI - Optical diagnosis of actinic cheilitis by infrared spectroscopy.
AB - : Actinic cheilitis (AC) is considered a potentially malignant disorder of the
lip. Biomolecular markers study is important to understand malignant
transformation into squamous cell carcinoma. Fourier transform infra red (FT-IR)
spectroscopy was used to analyze AC in this study. OBJECTIVES: The aim of the
study was to evaluate if FT-IR spectral regions of nucleic acids and collagen can
help in early diagnosis of malignant transformation. METHODS: Tissues biopsies of
14 patients diagnosed with AC and 14 normal tissues were obtained. FT-IR spectra
were measured at five different points resulting in 70 spectra of each. Analysis
of Principal components analysis (PCA) and linear discrimination analysis (LDA)
model were also used. In order to verify the statistical difference in the
spectra, Mann-Whitney U test was performed in each variable (wavenumber) with p
value <0.05. RESULTS: After the Mann-Whitney U test the vibrational modes of CO
(Collagen 1), PO2 (Nucleic Acids) and CO asymmetric (Triglycerides/Lipids) were
observed as a possible spectral biomarker. These bands were chosen because they
represent the vibrational modes related to collagen and DNA, which are supposed
to be changed in AC samples. Based on the PCA-LDA results, the predictive model
corresponding to the area under the curve was 0.91 for the fingerprint region and
0.83 for the high wavenumber region, showing the greater accuracy of the test.
CONCLUSIONS: FT-IR changes in collagen and nucleic acids could be used as
molecular biomarkers for malignant transformation.
PMID- 27491856
TI - The effectiveness and cost-effectiveness of intraoperative imaging in high-grade
glioma resection; a comparative review of intraoperative ALA, fluorescein,
ultrasound and MRI.
AB - BACKGROUND: Surgical resection of high-grade gliomas (HGG) is standard therapy
because it imparts significant progression free (PFS) and overall survival (OS).
However, HGG-tumor margins are indistinguishable from normal brain during
surgery. Hence intraoperative technology such as fluorescence (ALA, fluorescein)
and intraoperative ultrasound (IoUS) and MRI (IoMRI) has been deployed. This
study compares the effectiveness and cost-effectiveness of these technologies.
METHODS: Critical literature review and meta-analyses, using MEDLINE/PubMed
service. The list of references in each article was double-checked for any
missing references. We included all studies that reported the use of ALA,
fluorescein (FLCN), IoUS or IoMRI to guide HGG-surgery. The meta-analyses were
conducted according to statistical heterogeneity between studies. If there was no
heterogeneity, fixed effects model was used; otherwise, a random effects model
was used. Statistical heterogeneity was explored by chi2 and inconsistency (I2)
statistics. To assess cost-effectiveness, we calculated the incremental cost per
quality-adjusted life-year (QALY). RESULTS: Gross total resection (GTR) after
ALA, FLCN, IoUS and IoMRI was 69.1%, 84.4%, 73.4% and 70% respectively. The
differences were not statistically significant. All four techniques led to
significant prolongation of PFS and tended to prolong OS. However none of these
technologies led to significant prolongation of OS compared to controls. The
cost/QALY was $16,218, $3181, $6049 and $32,954 for ALA, FLCN, IoUS and IoMRI
respectively. CONCLUSIONS: ALA, FLCN, IoUS and IoMRI significantly improve GTR
and PFS of HGG. Their incremental cost was below the threshold for cost
effectiveness of HGG-therapy, denoting that each intraoperative technology was
cost-effective on its own.
PMID- 27491857
TI - [Arthroscopically assisted transcapsular refixation of the triangular
fibrocartilage complex of the wrist].
AB - OBJECTIVE: Refixation of the triangular fibrocartilage complex (TFCC) to the
ulnar capsule of the wrist. INDICATIONS: Distal TFCC tears without instability,
proximal TFCC intact. Loose ulnar TFCC attachment without tear or instability.
CONTRAINDICATIONS: Peripheral TFCC tears with instability of the distal
radioulnar joint (DRUJ). Complex or proximal tears of the TFCC. Isolated, central
degenerative tears without healing potential. SURGICAL TECHNIQUE:
Arthroscopically guided, minimally invasive suture of the TFCC to the base of the
sixth extensor compartment. POSTOPERATIVE MANAGEMENT: Above elbow plaster splint,
70 degrees flexion of the elbow joint, 45 degrees supination for 6 weeks. Skin
suture removal after 2 weeks. No physiotherapy to extend pronation and supination
during the first 3 months. RESULTS: In an ongoing long-term study, 7 of 31
patients who underwent transcapsular refixation of the TFCC between 1 January
2003 and 31 December 2010 were evaluated after an average follow-up interval of
116 +/- 34 months (range 68-152 months). All patients demonstrated an almost
nearly unrestricted range of wrist motion and grip strength compared to the
unaffected side. All distal radioulnar joints were stable. On the visual analogue
scale (VAS 0-10), pain at rest was 1 +/- 1 (range 0-2) and pain during exercise 2
+/- 2 (range 0-5); the DASH score averaged 10 +/- 14 points (range 0-39 points).
All patients were satisfied. The modified Mayo wrist score showed four excellent,
two good, and one fair result. These results correspond to the results of other
series. CONCLUSION: Transcapsular refixation is a reliable, technically simple
procedure in cases with ulnar-sided TFCC tears without instability leading to
good results.
PMID- 27491858
TI - Pb-210 and fly ash particles in ombrotrophic peat bogs as indicators of
industrial emissions.
AB - Peat cores were collected from a Sphagnum-dominated Selisoo bog, which is located
about 40 km from the large oil shale-fired power plants (PPs) in Estonia. These
PPs have been operational from the 1960's and had the largest negative impact on
the surrounding environment during the 1970's and 1980's. Nearby ombrotrophic
peatlands are good indicators of atmospheric pollution due to their properties of
effectively adsorbing mineral matter and pollutants. Collected peat cores (S1 and
S2) from Selisoo peat bog were sliced into 1 cm thick layers and measured gamma
spectrometrically. In addition, spherical fly ash particles (SFAP) originating
from the combustion of the PPs were counted. The maximum concentrations
(particles per cm3) of the SFAP remained between 7 and 12 cm for core S1 and
between 11 and 17 cm for core S2. The concentration profiles of the SFAP reflect
the combustion and emission history of the PPs. Pb-210 activity concentrations
have the maximum values up to 500 Bq kg-1 and 413 Bq m-2 for S1 and for the S2
the values are 441 Bq kg-1 and 535 Bq m-2 (dry weight). The unsupported 210Pb
inventory is around 4250 Bq m-2. This represents a 210Pb deposition flux of 133
Bq m-2 y-1. The estimated 210Pb deposition via fly ash from the PPs at Selisoo
area remains between 0.2 and 2.2 Bq m-2 y-1. Considering the annual 210Pb
deposition from the atmosphere (with a precipitation rate of 600 mm y-1) between
92 and 133 Bq m-2, which is regarded as the natural background value, we show
that the radiological burden due to the power plants at these distances is
negligible. As the peat cores exhibit noticeable differences from each other (in
terms of radionuclide concentration distribution), the SFAP can provide a good
additional parameter to improve the validity of results obtained only from
radiometric methods in the chronological studies. SFAP can also act as a possible
tool to estimate the radionuclide deposition rate via fly ash in the vicinity of
the PPs.
PMID- 27491859
TI - Spatial analysis of ambient gamma dose equivalent rate data by means of digital
image processing techniques.
AB - A detailed ambient gamma dose equivalent rate mapping based on field measurements
at ground level and at 1 m height was carried out at 142 sites in 80 * 90 km area
in Pest County, Hungary. Detailed digital image processing analysis was carried
out to identify and characterise spatial features such as outlying points,
anomalous zones and linear edges in a smoothed TIN interpolated surface. The
applied method proceeds from the simple shaded relief model and digital cross
sections to the more complex gradient magnitude and gradient direction maps, 2nd
derivative profile curvature map, relief map and lineament density map. Each map
is analysed for statistical characteristics and histogram-based image
segmentation is used to delineate areas homogeneous with respect to the parameter
values in these maps. Assessment of spatial anisotropy is implemented by 2D
autocorrelogram and directional variogram analyses. The identified spatial
features are related to underlying geological and tectonic conditions using GIS
technology. Results show that detailed digital image processing is efficient in
revealing the pattern present in field-measured ambient gamma dose equivalent
rates and they are related to regional scale tectonic zones and surface
sedimentary lithological conditions in the study area.
PMID- 27491860
TI - Frequent detection of PIK3CA mutations in single circulating tumor cells of
patients suffering from HER2-negative metastatic breast cancer.
AB - Modern technologies enable detection and characterization of circulating tumor
cells (CTC) in peripheral blood samples. Thus, CTC have attracted interest as
markers for therapeutic response in breast cancer. First studies have
incorporated CTC analyses to guide therapeutic interventions and stratification
of breast cancer patients. Aim of this study was to analyze characteristic
features of CTC as biomarker for predicting resistance to HER2-targeted
therapies. Therefore, CTC from metastatic breast cancer patients with HER2
negative primary tumors screened for the prospective randomized phase III trial
DETECT III were explored for their HER2 status and the presence of PIK3CA
mutations. Detection and characterization of HER2 expression of CTC were
conducted with the CellSearch((r)) system. Fifteen of 179 CTC-positive patients
(8.4%) contained >=1 CTC with strong HER2 expression. Genomic DNA from individual
CTC isolated by micromanipulation was propagated by whole genome amplification
and analyzed for PIK3CA mutations in exons 9 and 20 by Sanger sequencing. One or
more CTC/7.5 mL were detected in 179/290 patients (61.7%). In 109 patients
(34.8%), >=5 CTC/7.5 mL were found. We detected at least one CTC with the
mutation p.E542K, p.E545K, p.H1047R, p.H1047L or p.M1043V in 12/33 patients
(36.4%). Thirty six of 114 CTC (31.6%) harbored one of these mutations. CTC in
individual patients exhibited heterogeneity concerning PIK3CA mutations and HER2
expression. In conclusion, clinically relevant genomic aberrations such as
mutations in the hotspot regions of exon 9 and 20 of the PIK3CA gene can be
detected in single CTC and might provide insights into mechanisms of resistance
to HER2-targeted therapies.
PMID- 27491861
TI - LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with
aromatase inhibitor therapy outcome.
AB - BACKGROUND: PIK3CA is the most frequent somatic mutated oncogene in estrogen
receptor (ER) positive breast cancer. We previously observed an association
between PIK3CA genotype and aromatase inhibitors (AI) treatment outcome. This
study now evaluates whether expression of mRNAs and miRs are linked to PIK3CA
genotype and are independently related to AI therapy response in order to define
potential expressed biomarkers for treatment outcome. MATERIALS AND METHODS: The
miR and mRNA expression levels were evaluated for their relationship with the
PIK3CA genotype in two breast tumor datasets, i.e. 286 luminal cancers from the
TCGA consortium and our set of 84 ER positive primary tumors of metastatic breast
cancer patients who received first line AI. BRB Array tools class comparison was
performed to define miRs and mRNAs whose expression associate with PIK3CA exon 9
and 20 status. Spearman correlations established miR-mRNA pairs and mRNAs with
related expression. Next, a third dataset of 25 breast cancer patients receiving
neo-adjuvant letrozole was evaluated, to compare expression levels of identified
miRs and mRNAs in biopsies before and after treatment. Finally, to identify
potential biomarkers miR and mRNA levels were related with overall survival (OS)
and progression free survival (PFS) after first-line AI therapy. RESULTS:
Expression of 3 miRs (miR-449a, miR-205-5p, miR-301a-3p) and 9 mRNAs (CCNO,
FAM81B, LRG1, NEK10, PLCL1, PGR, SERPINA3, SORBS2, VTCN1) was related to the
PIK3CA status in both datasets. All except miR-301a-3p had an increased
expression in tumors with PIK3CA mutations. Validation in a publicly available
dataset showed that LRG1, PGR, and SERPINA3 levels were decreased after neo
adjuvant AI-treatment. Six miR-mRNA pairs correlated significantly and stepdown
analysis of all 12 factors revealed 3 mRNAs (PLCL1, LRG1, FAM81B) related to PFS.
Further analyses showed LRG1 and PLCL1 expression to be unrelated with luminal
subtype and to associate with OS and with PFS, the latter independent from
traditional predictive factors. CONCLUSION: We showed in two datasets of ER
positive and luminal breast tumors that the expression of 3 miRs and 9 mRNAs
associate with the PIK3CA status. Expression of LRG1 is independent of luminal (A
or B) subtype, decreased after neo-adjuvant AI-treatment, and is proposed as
potential biomarker for AI therapy outcome.
PMID- 27491862
TI - Cadmium resistance and uptake by bacterium, Salmonella enterica 43C, isolated
from industrial effluent.
AB - Cadmium resistant bacterium, isolated from industrial wastewater, was
characterized as Salmonella enterica 43C on the basis of biochemical and 16S rRNA
ribotyping. It is first ever reported S. enterica 43C bared extreme resistance
against heavy metal consortia in order of
Pb(2+)>Cd(2+)>As(3+)>Zn(2+)>Cr(6+)>Cu(2+)>Hg(2+). Cd(2+) stress altered growth
pattern of the bacterium in time dependent manner. It could remove nearly 57 %
Cd(2+) from the medium over a period of 8 days. Kinetic and thermodynamic studies
based on various adsorption isotherm models (Langmuir and Freundlich) depicted
the Cd(2+) biosorption as spontaneous, feasible and endothermic in nature.
Interestingly, the bacterium followed pseudo first order kinetics, making it a
good biosorbent for heavy metal ions. The S. enterica 43C Cd(2+) processivity was
significantly influenced by temperature, pH, initial Cd(2+) concentration,
biomass dosage and co-metal ions. FTIR analysis of the bacterium revealed the
active participation of amide and carbonyl moieties in Cd(2+) adsorption
confirmed by EDX analysis. Electron micrographs beckoned further surface
adsorption and increased bacterial size due to intracellular Cd(2+) accumulation.
An overwhelming increase in glutathione and other non-protein thiols levels
played a significant role in thriving oxidative stress generated by metal
cations. Presence of metallothionein clearly depicted the role of such proteins
in bacterial metal resistance mechanism. The present study results clearly
declare S. enterica 43C a suitable candidate for green chemistry to bioremediate
environmental Cd(2+).
PMID- 27491864
TI - Erratum.
AB - In the article "Effect of Addition of Platelet-rich Plasma to Calcium
Phosphosilicate Putty on Healing at 9 Months in Periodontal Intrabony Defects" by
Sagrika Shukla, Ashi Chug, Lanka Mahesh, Harpreet Singh Grover, issue 17 volume
3, page 230. It erroneously appeared that: "...support was given to Dr. George A.
Kotsakis DDS, Advanced Education Program in Periodontology, University of
Minnesota and Dr. Bhanu K. Bhakri MD (Paediatrics), All India Institute of
Medical Sciences for kind support and guidance." The correct statement is:
"Acknowledgements: We thank Dr. George A. Kotsakis DDS, Advanced Education
Program in Periodontology, University of Minnesota and Dr. Bhanu K. Bhakri MD
(Paediatrics), All India Institute of Medical Sciences for kind support and
guidance."
PMID- 27491863
TI - Can Simulated Team Tasks be Used to Improve Nontechnical Skills in the Operating
Room?
AB - OBJECTIVE: The purpose of this study was to understand the effect of a team-based
surgical skills intervention on the technical and nontechnical skills of surgery
residents. DESIGN: This was a prospective cohort study with pretesting or
posttesting. We designed basic tasks for the assessment and learning of
nontechnical skills in the operating room (OR). A total of 15 postgraduate year 1
residents performed an open gastrojejunostomy in a simulated OR setting
(pretest), followed by training in the 3 team-based tasks designed to teach
communication and teamwork, followed by performance of a gastrojejunostomy in the
simulated OR (posttest). SETTING: Tertiary care, university-based teaching
institution. PARTICIPANTS: A total of 15 general surgery residents at the intern
level. RESULTS: The mean nontechnical skills for surgeons (NOTSS) score improved
postteam task training (10.04 +/- 0.33 vs. 12.14 +/- 1.33). There was a
concomitant increase in the objective structured assessment of technical skills
(OSATS) score (18.56 +/- 0.86 vs. 22.86 +/- 0.15, p = 0.006). The percentage
increases in OSATS and NOTSS score for each resident was similar (19.49 +/- 4.8 %
for NOTSS vs. 21.22 +/- 4.92 % for OSATS, p = 0.502). CONCLUSION: Nontechnical
skills positively correlate with the technical performance of a surgeon. Simple,
easily designed tasks can be used to improve NOTSS in the OR. These team tasks
and development of curricula based on them can be used to explicitly address one
of the most important components of ACGME core competencies for surgical
residents, namely interpersonal skills and communication.
PMID- 27491865
TI - Main causes of death in Dande, Angola: results from Verbal Autopsies of deaths
occurring during 2009-2012.
AB - BACKGROUND: The Dande Health and Demographic Surveillance System (HDSS) located
in Bengo Province, Angola, covers nearly 65,500 residents living in approximately
19,800 households. This study aims to describe the main causes of deaths (CoD)
occurred within the HDSS, from 2009 to 2012, and to explore associations between
demographic or socioeconomic factors and broad mortality groups (Group I
Communicable diseases, maternal, perinatal and nutritional conditions; Group II
Non-communicable diseases; Group III-Injuries; IND-Indeterminate). METHODS:
Verbal Autopsies (VA) were performed after death identification during routine
HDSS visits. Associations between broad groups of CoD and sex, age, education,
socioeconomic position, place of residence and place of death, were explored
using chi-square tests and fitting logistic regression models. RESULTS: From a
total of 1488 deaths registered, 1009 verbal autopsies were performed and 798 of
these were assigned a CoD based on the 10(th) revision of the International
Classification of Diseases (ICD-10). Mortality was led by CD (61.0 %), followed
by IND (18.3 %), NCD (11.6 %) and INJ (9.1 %). Intestinal infectious diseases,
malnutrition and acute respiratory infections were the main contributors to under
five mortality (44.2 %). Malaria was the most common CoD among children under 15
years old (38.6 %). Tuberculosis, traffic accidents and malaria led the CoD among
adults aged 15-49 (13.5 %, 10.5 % and 8.0 % respectively). Among adults aged 50
or more, diseases of the circulatory system (23.2 %) were the major CoD, followed
by tuberculosis (8.2 %) and malaria (7.7 %). CD were more frequent CoD among less
educated people (adjusted odds ratio, 95 % confidence interval for none vs. 5 or
more years of school: 1.68, 1.04-2.72). CONCLUSION: Infectious diseases were the
leading CoD in this region. Verbal autopsies proved useful to identify the main
CoD, being an important tool in settings where vital statistics are scarce and
death registration systems have limitations.
PMID- 27491866
TI - Interaction of a standardized mistletoe (Viscum album) preparation with antitumor
effects of Trastuzumab in vitro.
AB - BACKGROUND: Besides conventional anticancer therapy many breast cancer patients
use complementary and alternative medicine (CAM) like the medicinal herb
mistletoe (Viscum album L.). To gain more knowledge about possible herb-drug
interactions between CAM and conventional anticancer medications, in the present
in vitro study we investigated the effect of a standardized mistletoe preparation
on the action of Trastuzumab, a drug used for the treatment of Her-2 positive
breast cancer. METHODS: The Her-2 positive human breast carcinoma cell line SK-BR
3 was treated with Trastuzumab. Different doses of the drug were combined with
Viscum album extract (VAE) in clinically relevant doses. Proliferation,
apoptosis, cell cycle and the secretion of vascular endothelial growth factor
(VEGF) were analyzed. RESULTS: No inhibition of antitumor efficacy of Trastuzumab
by VAE was detected. VAE and Trastuzumab, either alone or in combination,
inhibited proliferation of SK-BR-3 cells in vitro. At higher concentrations VAE
induced apoptosis, which was not observed for Trastuzumab. Cells treated with
Trastuzumab underwent a G0/G1 cell cycle arrest and cells treated with VAE a G2/M
arrest. After application of the two drugs in combination both G0/G1 and G2/M
arrest was observed. VEGF secretion of SK-BR-3 cells was significantly inhibited
by sole treatment with Trastuzumab or VAE. Combined treatment of Trastuzumab and
VAE at clinically relevant doses showed additive inhibitory effects on VEGF
secretion. CONCLUSIONS: VAE did not interfere with cytostatic effects of
Trastuzumab on SK-BR-3 cells in vitro. Our in vitro results suggest that no risk
of safety by herb drug interactions has to be expected from the exposition of
cancer cells to Trastuzumab and VAE simultaneously. In contrast, VAE and
Trastuzumab seem to exhibit complementary anti-cancer effects in vitro.
PMID- 27491867
TI - Spine extra-osseous chordoma mimicking neurogenic tumors: report of three cases
and review of the literatures.
AB - BACKGROUND: For a long time, chordoma has been known as an osseous tumor mainly
found at the clivus and sacrococcygeal region. However, spine extra-osseous
chordoma (SEC) with a better prognosis than the classic type has been neglected.
According to our literature review, only several case reports have been published
in English literatures. Here in this article, three cases of SEC, plus a
literature review, are presented. CASE PRESENTATION: Three cases of SEC were
presented from our center. Surprisingly, neurologic tumors were considered as the
first diagnosis. Thereafter, en bloc resection was performed in all the three
cases. Especially, the dumbbell-shaped one in the cervical spine was removed by
en bloc through the combined anterior and posterior approach for the first time.
Follow-up within 12-58 months after surgeries proved no recurrence or metastasis.
CONCLUSIONS: Spine extra-osseous chordoma, commonly located in the cervical and
epidural region, is extremely rarely met. SEC is characterized with less
aggressiveness, the lower rate of recurrence and metastasis, and better prognosis
than those of the osseous origin. Though complete excision can be achieved
generally, differential diagnosis of spine neurogenic tumors and the following en
bloc resection should be made as carefully as possible.
PMID- 27491868
TI - Comparative efficacy of oral nucleotide analogues for the prophylaxis of
hepatitis B virus recurrence after liver transplantation: a network meta
analysis.
AB - BACKGROUND: Prophylactic nucleos(t)ide anologues against hepatitis B virus (HBV)
recurrence after liver transplantation (LT) include lamivudine, entecavir,
tenofovir, adefovir. Since the most effective strategies for post-LT remain
inconclusive, we aimed to compare 6 different treatment options (lamivudine,
entecavir, tenofovir, adefovir, lamivudine plus adefovir, lamivudine plus
tenofovir) in terms of HBV recurrence after LT using network meta-analysis.
METHODS: The search identified seventeen studies involving 6 different
prophylactic regimens covering 7274 patients. RESULTS: Compared with entecavir,
lamivudine plus tenofovir (OR 2.00, 95%CI 0.02-183.29), lamivudine plus adefovir,
(OR 2.83, 95%CI 0.18-33.57), tenofovir (OR 1.11, 95%CI 0.22-5.80), adefovir (OR
3.78, 95%CI 0.59-22.16), lamivudine (OR 4.62, 95%CI 1.75-11.39) were associated
with an increased risk of HBV recurrence. CONCLUSION: Entecavir resulted with the
highest probability (31%) as the best prophylactic option on reducing the risk of
HBV recurrence. Entecavir is the preferred oral NAs treatment compared to other
five different prophylactic regimens in the prevention of HBV recurrence after
LT.
PMID- 27491869
TI - Erratum to: Antioxidant Rescue of Selenomethionine-Induced Teratogenesis in
Zebrafish Embryos.
PMID- 27491870
TI - Sub-lethal Effects of Chlorpyrifos on Big Brown Bats (Eptesicus fuscus).
AB - We determined dose-response curves for sublethal effects of the organophosphorus
(OP) insecticide, chlorpyrifos, on bats. Big brown bats (Eptesicus fuscus, n =
64) were given a single dose of chlorpyrifos (nominal concentrations) of 0, 5,
10, 15, 20, 25, 30, or 60 ug/g body weight and examined at 12 or 24 h after
dosing. A second experiment dosed 32 bats with 0 or 60 ug/g body weight and
examined 1, 3, 7, or 14 days after dosing. Skin temperature and behavioral
changes were recorded, and brain and plasma cholinesterase (ChE) activity were
measured. The benchmark dose (BMD10) of chlorpyrifos that altered brain and
plasma ChE activity at 24 h was 3.7 and 10.1 ug/g, respectively. The 95 % lower
confidence limit for the BMD10 (i.e., BMDL10) was 1.6 and 7.7 ug/g. The best of
five models (as determined by AIC) for impaired flight, impaired movement, or
presence of tremors provided a BMD10 of 6.2, 12.9, and 7.8 ug/g body weight of
chlorpyrifos, respectively. BMDL10 for impaired flight, impaired movement, or
presence of tremors was 3.5, 6.6, and 5.3 ug/g body weight, respectively. In the
wild, impaired ability to fly or crawl could be life-threatening. Brain and
plasma ChE activity remained low for 3 days after dosing. Gradual recovery of
enzyme activity was observed by 7 days in survivors. Brain and plasma ChE
activity were still significantly lower than that of the control group at 14 days
after dosing.
PMID- 27491871
TI - Enhanced spin-orbit coupling in core/shell nanowires.
AB - The spin-orbit coupling (SOC) in semiconductors is strongly influenced by
structural asymmetries, as prominently observed in bulk crystal structures that
lack inversion symmetry. Here we study an additional effect on the SOC: the
asymmetry induced by the large interface area between a nanowire core and its
surrounding shell. Our experiments on purely wurtzite GaAs/AlGaAs core/shell
nanowires demonstrate optical spin injection into a single free-standing nanowire
and determine the effective electron g-factor of the hexagonal GaAs wurtzite
phase. The spin relaxation is highly anisotropic in time-resolved micro
photoluminescence measurements on single nanowires, showing a significant
increase of spin relaxation in external magnetic fields. This behaviour is
counterintuitive compared with bulk wurtzite crystals. We present a model for the
observed electron spin dynamics highlighting the dominant role of the interface
induced SOC in these core/shell nanowires. This enhanced SOC may represent an
interesting tuning parameter for the implementation of spin-orbitronic concepts
in semiconductor-based structures.
PMID- 27491872
TI - Linear Multiple Epithelioid Hemangioma Associated With a Quiescent Vascular
Malformation.
PMID- 27491873
TI - Quantification of global myocardial function by cine MRI deformable registration
based analysis: Comparison with MR feature tracking and speckle-tracking
echocardiography.
AB - OBJECTIVES: To evaluate deformable registration algorithms (DRA)-based
quantification of cine steady-state free-precession (SSFP) for myocardial strain
assessment in comparison with feature-tracking (FT) and speckle-tracking
echocardiography (STE). METHODS: Data sets of 28 patients/10 volunteers,
undergoing same-day 1.5T cardiac MRI and echocardiography were included. LV
global longitudinal (GLS), circumferential (GCS) and radial (GRS) peak systolic
strain were assessed on cine SSFP data using commercially available FT algorithms
and prototype DRA-based algorithms. STE was applied as standard of reference for
accuracy, precision and intra-/interobserver reproducibility testing. RESULTS:
DRA showed narrower limits of agreement compared to STE for GLS (-4.0 [-0.9,
7.9]) and GCS (-5.1 [1.1,-11.2]) than FT (3.2 [11.2,-4.9]; 3.8 [13.9,-6.3],
respectively). While both DRA and FT demonstrated significant differences to STE
for GLS and GCS (all p<0.001), only DRA correlated significantly to STE for GLS
(r=0.47; p=0.006). However, good correlation was demonstrated between MR
techniques (GLS:r=0.74; GCS:r=0.80; GRS:r=0.45, all p<0.05). Comparing DRA with
FT, intra-/interobserver coefficient of variance was lower (1.6 %/3.2 % vs. 6.4
%/5.7 %) and intraclass-correlation coefficient was higher. DRA GCS and GRS data
presented zero variability for repeated observations. CONCLUSIONS: DRA is an
automated method that allows myocardial deformation assessment with superior
reproducibility compared to FT. KEY POINTS: * Inverse deformable registration
algorithms (DRA) allow myocardial strain analysis on cine MRI. * Inverse DRA
demonstrated superior reproducibility compared to feature-tracking (FT) methods.
* Cine MR DRA and FT analysis demonstrate differences to speckle-tracking
echocardiography * DRA demonstrated better correlation with STE than FT for MR
derived global strain data.
PMID- 27491874
TI - Multiparametric magnetic resonance imaging characteristics of normal, benign and
malignant conditions in the prostate.
AB - OBJECTIVES: To identify the multiparametric magnetic resonance imaging (mpMRI)
characteristics of normal, benign and malignant conditions in the prostate.
METHODS: Fifty-six histopathological whole-mount radical prostatectomy specimens
from ten randomly selected patients with prostate cancer (PC) were matched with
corresponding transverse mpMRI slices. The mpMRI was performed prior to biopsy
and consisted of T2-weighted imaging (T2-WI), diffusion-weighted imaging (DWI),
dynamic contrast-enhanced imaging (DCE) and magnetic resonance spectroscopic
imaging (MRSI). RESULTS: In each prostate specimen, a wide range of
histopathological conditions were observed. They showed consistent but
overlapping characteristics on mpMRI. Normal glands in the transition zone showed
lower signal intensity (SI) on T2-WI, lower ADC values and lower citrate peaks on
MRSI as compared to the peripheral zone (PZ) due to sparser glandular elements
and more prominent collagenous fibres. In the PZ, normal glands were iso-intense
on T2-WI, while high SI areas represented cystic atrophy. Mimickers of well
differentiated PC on mpMRI were inflammation, adenosis, HG-PIN and post-atrophic
hyperplasia. CONCLUSION: Each prostate is a unique mix of normal, benign and/or
malignant areas that vary in extent and distribution resulting in very
heterogeneous characteristics on mpMRI. Understanding the main concepts of this
mpMRI-histopathological correlation may increase the diagnostic confidence in
reporting mpMRI. KEYPOINTS: * In each prostate specimen a wide range of
histopathological conditions was observed. * Interpretation of mpMRI may be
difficult because benign conditions may mimic PC. * High signal intensity areas
in the PZ on T2-WI represented cystic atrophy. * The TZ showed sparser glands and
more collagenous fibres than the PZ.
PMID- 27491875
TI - Volumetric MRI study of the intrauterine growth restriction fetal brain.
AB - OBJECTIVES: Intrauterine growth restriction (IUGR) is a pathologic fetal
condition known to affect the fetal brain regionally and associated with future
neurodevelopmental abnormalities. This study employed MRI to assess in utero
regional brain volume changes in IUGR fetuses compared to controls. METHODS:
Retrospectively, using MRI images of fetuses at 30-34 weeks gestational age, a
total of 8 brain regions-supratentorial brain and cavity, cerebral hemispheres,
temporal lobes and cerebellum-were measured for volume in 13 fetuses with IUGR
due to placental insufficiency and in 21 controls. Volumes and their ratios were
assessed for difference using regression models. Reliability was assessed by
intraclass correlation coefficients (ICC) between two observers. RESULTS: In both
groups, all structures increase in absolute volume during that gestation period,
and the rate of cerebellar growth is higher compared to that of supratentorial
structures. All structures' absolute volumes were significantly smaller for the
IUGR group. Cerebellar to supratentorial ratios were found to be significantly
smaller (P < 0.05) for IUGR compared to controls. No other significant ratio
differences were found. ICC showed excellent agreement. CONCLUSIONS: The
cerebellar to supratentorial volume ratio is affected in IUGR fetuses. Additional
research is needed to assess this as a radiologic marker in relation to long-term
outcome. KEY POINTS: * IUGR is a pathologic fetal condition affecting the brain *
IUGR is associated with long-term neurodevelopmental abnormalities; fetal
characterization is needed * This study aimed to evaluate regional brain volume
differences in IUGR * Cerebellar to supratentorial volume ratios were smaller in
IUGR fetuses * This finding may play a role in long-term development of IUGR
fetuses.
PMID- 27491876
TI - A simplified method for identifying early CRISPR-induced indels in zebrafish
embryos using High Resolution Melting analysis.
AB - BACKGROUND: The CRISPR/Cas9 system has become a regularly used tool for editing
the genome of many model organisms at specific sites. However, two limiting steps
arise in the process of validating guide RNA target sites in larvae and adults:
the time required to identify indels and the cost associated with identifying
potential mutant animals. RESULTS: Here we have combined and optimized the
HotSHOT genomic DNA extraction technique with a two-steps Evagreen PCR, followed
by a high-resolution melting (HRM) assay, which facilitates rapid identification
of CRISPR-induced indels. With this technique, we were able to genotype adult
zebrafish using genomic DNA extracted from fin-clips in less than 2 h. We were
also able to obtain a reliable and early read-out of the effectiveness of guide
RNAs only 4 h after the embryos were injected with the constructs for the
CRISPR/Cas9 mutagenic system. Furthermore, through mutagenesis kinetic assay, we
identified that the 2-cell stage is the earliest time point at which indels can
be observed. CONCLUSIONS: By combining an inexpensive and rapid genomic DNA
extraction method with an HRM-based assay, our approach allows for high
throughput genotyping of adult zebrafish and embryos, and is more sensitive than
standard PCR approaches, permitting early identification of CRISPR-induced indels
and with applications for other model organisms as well.
PMID- 27491877
TI - A special issue on CCN proteins and cancer.
PMID- 27491878
TI - Transcranial Doppler as a Predictor of Ischemic Events in Carotid Artery
Dissection.
AB - BACKGROUND: We aim to evaluate clinical features and transcranial Doppler (TCD)
elements, as predictors of the development of ischemic events (IEs) in patients
suffering from spontaneous carotid arterial dissection without stroke (CCADW).
METHODS: Consecutive patients with CCADW, seen in Clinica Alemana de Santiago
between April 2004 and January 2015, were evaluated clinically, and with TCD,
microembolic signals (MES) monitoring and breath hold Index (BHI) test were
performed. RESULTS: Forty-one patients with 45 CCADW were included. Mean age 41.9
years, 31 male, and 12 (29.1%) patients present with multiple CCADW. At the
moment of TCD evaluation, 17 (41.4%) patients were being treated with
antiplatelets and the rest under Heparin. TCD monitoring lasted in average 53.3
minutes and demonstrated at the moment of evaluation, MES in four carotid
arteries (11.1%) of 3 patients and 13 (28.8%) abnormal BHI in 11 patients. Six
IEs occurred in 3 patients, 3 strokes, and 3 transient ischemic attacks. In the
univariate analysis correlating IE with clinical and ultrasonographic findings,
the degree of carotid stenosis, the presence of multiple CAD, and the presence of
MES plus abnormalities of BHI were significantly associated with the risk of an
IE. Multivariable analysis showed that only the presence of MES plus abnormal BHI
were significant (P < .001). MES and abnormal BHI were present in the 3 patients
and in four arterial territories that had IE. CONCLUSIONS: TCD can identify a
subgroup of patients with CCADW who are at high risk of IE.
PMID- 27491880
TI - Nanofibrillar cellulose wound dressing in skin graft donor site treatment.
AB - BACKGROUND: Although new therapeutic approaches for burn treatment have made
progress, there is still need for better methods to enhance wound healing and
recovery especially in severely burned patients. Nanofibrillar cellulose (NFC)
has gained attention due to its renewable nature, good biocompatibility and
excellent physical properties that are of importance for a range of applications
in pharmaceutical and biomedical fields. In the present study, we investigated
the potential of a wood based NFC wound dressing in a clinical trial on burn
patients. Previously, we have investigated NFC as a topical functionalized wound
dressing that contributes to improve wound healing in mice. METHODS: Wood based
NFC wound dressing was tested in split-thickness skin graft donor site treatment
for nine burn patients in clinical trials at Helsinki Burn Centre. NFC dressing
was applied to split thickness skin graft donor sites. The dressing gradually
dehydrated and attached to donor site during the first days. During the clinical
trials, physical and mechanical properties of NFC wound dressing were optimized
by changing its composition. From patient 5 forward, NFC dressing was compared to
commercial lactocapromer dressing, Suprathel(r) (PMI Polymedics, Germany).
RESULTS: Epithelialization of the NFC dressing-covered donor site was faster in
comparison to Suprathel(r). Healthy epithelialized skin was revealed under the
detached NFC dressing. NFC dressing self-detached after 11-21days for patients 1
9, while Suprathel(r) self-detached after 16-28days for patients 5-9. In
comparison studies with patients 5-9, NFC dressing self-detached on average 4days
earlier compared with Suprathel(r). Lower NFC content in the material was
evaluated to influence the enhanced pliability of the dressing and attachment to
the wound bed. No allergic reaction or inflammatory response to NFC was observed.
NFC dressing did not cause more pain for patients than the traditional methods to
treat the skin graft donor sites. CONCLUSION: Based on the preliminary clinical
data, NFC dressing seems to be promising for skin graft donor site treatment
since it is biocompatible, attaches easily to wound bed, and remains in place
until donor site has renewed. It also detaches from the epithelialized skin by
itself.
PMID- 27491879
TI - Reproductive age-associated fibrosis in the stroma of the mammalian ovary.
AB - Under normal physiological conditions, tissue remodeling in response to injury
leads to tissue regeneration without permanent damage. However, if homeostasis
between synthesis and degradation of extracellular matrix (ECM) components is
altered, fibrosis - or the excess accumulation of ECM - can disrupt tissue
architecture and function. Several organs, including the heart, lung and kidney,
exhibit age-associated fibrosis. Here we investigated whether fibrosis underlies
aging in the ovary - an organ that ages chronologically before other organs. We
used Picrosirius Red (PSR), a connective tissue stain specific for collagen I and
III fibers, to evaluate ovarian fibrosis. Using bright-field, epifluorescence,
confocal and polarized light microscopy, we validated the specific staining of
highly ordered PSR-stained fibers in the ovary. We next examined ovarian PSR
staining in two mouse strains (CD1 and CB6F1) across an aging continuum and found
that PSR staining was minimal in ovaries from reproductively young adult animals,
increased in distinct foci in animals of mid-to-advanced reproductive age, and
was prominent throughout the stroma of the oldest animals. Consistent with
fibrosis, there was a reproductive age-associated increase in ovarian
hydroxyproline content. We also observed a unique population of multinucleated
macrophage giant cells, which are associated with chronic inflammation, within
the ovarian stroma exclusively in reproductively old mice. In fact, several genes
central to inflammation had significantly higher levels of expression in ovaries
from reproductively old mice relative to young mice. These results establish
fibrosis as an early hallmark of the aging ovarian stroma, and this altered
microenvironment may contribute to the age-associated decline in gamete quality.
PMID- 27491881
TI - Immunomodulation of hematological malignancies using oligonucleotides based
nanomedicines.
AB - Hematological malignancies are a group of diseases characterized by clonal
proliferation of blood-forming cells. Malignant blood cells are classified as
myeloid or lymphoid cells depending on their stem cell origin. Lymphoid
malignancies are characterized by lymphocyte accumulation in the blood stream, in
the bone marrow, or in lymphatic nodes and organs. Several of these diseases are
associated with chromosomal translocations, which cause gene fusion and
amplification of expression, while others are characterized with aberrant
expression of oncogenes. Overall, these genes play a major role in development
and maintenance of malignant clones. The discovery of antisense oligonucleotides
and RNA interference (RNAi) mechanisms offer new tools to specifically manipulate
gene expression. Systemic delivery of inhibitory oligonucleotides molecules for
manipulation of gene expression in lymphocytes holds a great potential for
facilitating the development of an oligonucleotides -based therapy platform for
lymphoid blood cancer. However, lymphocytes are among the most difficult targets
for oligonucleotides delivery, as they are resistant to conventional transfection
reagents and are dispersed throughout the body, making it difficult to
successfully localize or deliver oligonucleotides payloads via systemic
administration. In this review, we will survey the latest progress in the field
of oligonucleotides based nanomedicine in the heterogeneous group of
hematological malignancies with special emphasis on RNA based strategies. We will
describe the most advanced non-viral nanocarriers for RNA delivery to malignant
blood cells. We will also discuss targeted strategies for cell specific delivery
of RNA molecules using nanoparticles and the therapeutic benefit of manipulating
gene function in hematological malignancies. Finally, we will focus on the ex
vivo, in vivo, and clinical trial strategies, that are currently under
development in hematological malignancies - strategies that might increase the
arsenal of drugs available to hematologists in the upcoming years.
PMID- 27491882
TI - Therapeutic and diagnostic applications of extracellular vesicles.
AB - During the past two decades, extracellular vesicles (EVs) have been identified as
important mediators of intercellular communication, enabling the functional
transfer of bioactive molecules from one cell to another. Consequently, it is
becoming increasingly clear that these vesicles are involved in many
(patho)physiological processes, providing opportunities for therapeutic
applications. Moreover, it is known that the molecular composition of EVs
reflects the physiological status of the producing cell and tissue, rationalizing
their exploitation as biomarkers in various diseases. In this review the
composition, biogenesis and diversity of EVs is discussed in a therapeutic and
diagnostic context. We describe emerging therapeutic applications, including the
use of EVs as drug delivery vehicles and as cell-free vaccines, and reflect on
future challenges for clinical translation. Finally, we discuss the use of EVs as
a biomarker source and highlight recent studies and clinical successes.
PMID- 27491883
TI - Nilotinib reverses ABCB1/P-glycoprotein-mediated multidrug resistance but
increases cardiotoxicity of doxorubicin in a MDR xenograft model.
AB - The BCR-Abl tyrosine kinase inhibitor (TKI), nilotinib, was developed to surmount
resistance or intolerance to imatinib in patients with Philadelphia-positive
chronic myelogenous leukemia. Recent studies have shown that nilotinib induces
potent sensitization to anticancer agents by blocking the functions of ABCB1/P
glycoprotein (P-gp) in multidrug resistance (MDR). However, changes in P-gp
expression or function affect the cardiac disposition and prolong the presence of
both doxorubicin (DOX) and doxorubicinol (DOXol) in cardiac tissue, thus,
enhancing the risk of cardiotoxicity. In this study, we used a MDR xenograft
model to evaluate the antitumor activity, tissue distribution and cardiotoxicity
of DOX when co-administered with nilotinib. This information will provide more
insight into the pharmacological role of nilotinib in MDR reversal and the risk
of DOX cardiotoxicity. Our results showed that nilotinib significantly enhanced
DOX cytotoxicity and increased intracellular rhodamine 123 accumulation in
MG63/DOX cells in vitro and strongly enhanced DOX inhibition of growth of P-gp
overexpressing MG63/DOX cell xenografts in nude mice. Additionally, nilotinib
significantly increased DOX and DOXol accumulation in serum, heart, liver and
tumor tissues. Importantly, nilotinib induced a disproportionate increase in
DOXol in cardiac tissue. In the co-administration group, CBR1 and AKR1A1 protein
levels were significantly increased in cardiac tissue, with more severe necrosis
and vacuole formation. These results indicate that nilotinib reverses P-gp-
mediated MDR by blocking the efflux function and potentiates DOX-induced
cardiotoxicity. These findings represent a guide for the design of future
clinical trials and studies of pharmacokinetic interactions and may be useful in
guiding the use of nilotinib in combination therapy of cancer in clinical
practice.
PMID- 27491884
TI - Estimation of bisphenol A-Human toxicity by 3D cell culture arrays, high
throughput alternatives to animal tests.
AB - Bisphenol A (BPA) has been widely used for manufacturing polycarbonate plastics
and epoxy resins and has been extensively tested in animals to predict human
toxicity. In order to reduce the use of animals for toxicity assessment and
provide further accurate information on BPA toxicity in humans, we encapsulated
Hep3B human hepatoma cells in alginate and cultured them in three dimensions (3D)
on a micropillar chip coupled to a panel of metabolic enzymes on a microwell
chip. As a result, we were able to assess the toxicity of BPA under various
metabolic enzyme conditions using a high-throughput and micro assay; sample
volumes were nearly 2,000 times less than that required for a 96-well plate. We
applied a total of 28 different enzymes to each chip, including 10 cytochrome
P450s (CYP450s), 10 UDP-glycosyltransferases (UGTs), 3 sulfotransferases (SULTs),
alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Phase I enzyme
mixtures, phase II enzyme mixtures, and a combination of phase I and phase II
enzymes were also applied to the chip. BPA toxicity was higher in samples
containing CYP2E1 than controls, which contained no enzymes (IC50, 184+/-16MUM
and 270+/-25.8MUM, respectively, p<0.01). However, BPA-induced toxicity was
alleviated in the presence of ADH (IC50, 337+/-17.9MUM), ALDH2 (335+/-13.9MUM),
and SULT1E1 (318+/-17.7MUM) (p<0.05). CYP2E1-mediated cytotoxicity was confirmed
by quantifying unmetabolized BPA using HPLC/FD. Therefore, we suggest the present
micropillar/microwell chip platform as an effective alternative to animal testing
for estimating BPA toxicity via human metabolic systems.
PMID- 27491887
TI - Introduction to the Special Section on Clinical Applications of Multi-Scale
Modeling.
PMID- 27491885
TI - Effects of Sialic Acid Modifications on Virus Binding and Infection.
AB - Sialic acids (Sias) are abundantly displayed on the surfaces of vertebrate cells,
and particularly on all mucosal surfaces. Sias interact with microbes of many
types, and are the targets of specific recognition by many different viruses.
They may mediate virus binding and infection of cells, or alternatively can act
as decoy receptors that bind virions and block virus infection. These nine-carbon
backbone monosaccharides naturally occur in many different modified forms, and
are attached to underlying glycans through varied linkages, creating significant
diversity in the pathogen receptor forms. Here we review the current knowledge
regarding the distribution of modified Sias in different vertebrate hosts,
tissues, and cells, their effects on viral pathogens where those have been
examined, and outline unresolved questions.
PMID- 27491888
TI - Persistent Luminescent Nanocarrier as an Accurate Tracker in Vivo for Near
Infrared-Remote Selectively Triggered Photothermal Therapy.
AB - Optical imaging-guidance of indocyanine green (ICG) for photothermal therapy
(PTT) has great latent capacity in cancer therapy. However, the conventional
optical image-guidance mode has caused strong tissue autofluorescence of the
living tissue, which leads to the accurate infrared light irradiation cannot be
conducted. In this article, ICG and persistent luminescence phosphors (PLPs)
coloaded mesoporous silica nanocarriers ((ICG+PLPs)@mSiO2) were first designed
and prepared for persistent luminescent imaging-guided PTT. The (ICG+PLPs)@mSiO2
nanocarriers could significantly improve signal-to-noise ratio during
luminescence imaging-guided PTT, making the PLP promising for improving the
accuracy of the tumor site for photothermal therapy in vivo. This paper is likely
to develop a new way for accurately regulating cancer cell death based on
luminescence imaging-guided PTT selectively triggered by near-infrared (NIR)
remote.
PMID- 27491889
TI - Attendance of cultural events and involvement with the arts-impact evaluation on
health and well-being from a Swiss household panel survey.
AB - OBJECTIVES: Although there is strong uptake of active or passive engagement with
the cultural and creative activities as determinants of individual health, well
being and social participation, few population studies report any causal
influence on self-reported and physical health or life satisfaction from
voluntary engagement with the arts (playing an instrument or singing, painting,
sculpture) or passive cultural participation (attending the cinema, theatre,
opera and exhibitions). This study set out to investigate any potential derived
benefits to the Swiss population. STUDY DESIGN: The 2010 and 2013 waves of the
Swiss Household Panel study were used for analysis. The data are representative
for the Swiss population aged 14 years and older with respect to major
demographic variables. METHODS: Using longitudinal data, the strengths of the two
approaches to evaluating causal inference were simultaneously applied: propensity
score matching and difference-in-differences. Propensity score matching attempted
to eliminate selection bias by conditioning on confounding variables. Difference
in-differences estimator was applied to remove unobserved fixed effects via intra
individual comparisons over time by comparing the trends in a matched treatment
and control group. RESULTS: The study showed that voluntary cultural activity-of
any type, passive or active-did not seem to have any causative influence on
health and well-being. Results showed that long-term health and well-being did
not improve significantly as a result of any specific activity in the cultural
arena. CONCLUSIONS: The investigation provided little evidence to justify health
promotion messages for involvement with the arts. Nevertheless, these findings do
not contest that active or passive participation in cultural- and arts-related
activities may be beneficial to health and well-being when guided by qualified
therapists to treat specific health-related problems.
PMID- 27491886
TI - Natural Products and the Gene Cluster Revolution.
AB - Genome sequencing has created unprecedented opportunities for natural-product
discovery and new insight into the diversity and distributions of natural-product
biosynthetic gene clusters (BGCs). These gene collectives are highly evolved for
horizontal exchange, thus providing immediate opportunities to test the effects
of small molecules on fitness. The marine actinomycete genus Salinispora
maintains extraordinary levels of BGC diversity and has become a useful model for
studies of secondary metabolism. Most Salinispora BGCs are observed infrequently,
resulting in high population-level diversity while conforming to constraints
associated with maximum genome size. Comparative genomics is providing a
mechanism to assess secondary metabolism in the context of evolution and evidence
that some products represent ecotype-defining traits while others appear
selectively neutral.
PMID- 27491890
TI - Shedding light on azopolymer brush dynamics by fluorescence correlation
spectroscopy.
AB - Understanding the response to illumination at a molecular level as well as
characterising polymer brush dynamics are key features that guide the engineering
of new light-stimuli responsive materials. Here, we report on the use of a
confocal microscopy technique that was exploited to discern how a single
molecular event such as the photoinduced isomerisation of azobenzene can affect
an entire polymeric material at a macroscopic level leading to photodriven mass
migration. For this reason, a set of polymer brushes, containing azobenzene
(Disperse Red 1, DR) on the side chains of poly(methacrylic acid), was
synthesised and the influence of DR on the polymer brush dynamics was
investigated for the first time by Fluorescence Correlation Spectroscopy (FCS).
Briefly, two dynamics were observed, a short one coming from the isomerisation of
DR and a long one related to the brush main chain. Interestingly, photoinduced
polymer aggregation in the confocal volume was observed.
PMID- 27491891
TI - Pyrogallol, an absorbable microbial gallotannins-metabolite and mango polyphenols
(Mangifera Indica L.) suppress breast cancer ductal carcinoma in situ
proliferation in vitro.
AB - Mango is rich in bioactive absorbable polyphenols, but also contains considerable
amounts of unabsorbable gallotannins at varying degrees of polymerization.
Gallotannins are not absorbable upon consumption and have rarely been considered
in the discussion of health benefits of polyphenols. Therefore, the objective of
this study was to investigate the anti-proliferative activities of the major
microbial metabolite of gallotannins, pyrogallol (PG) and a low molecular weight
fraction of mango (Mangifera Indica L.) polyphenols (ML) and involved pathways
including the AKT/mTOR signaling axis in an in situ breast cancer cell line,
MCF10DCIS.COM. Fluorouracil (5-FU), a widely used genotoxic cancer therapeutic,
was used a positive control and in combination with ML and PG to assess potential
interactions. Concentrations that were non-cytotoxic in non-cancer cells were
identified in non-cancer mammary fibroblasts (MCF-12F) and only non-cytotoxic
dietarily relevant concentrations were selected for the investigation in
MCF10DCIS.COM cancer cells. In addition to proliferation and viability, mRNA and
expression of total and phosphorylated protein were investigated. Results show
that both, ML and PG significantly reduced proliferation in MCF10DCIS.COM, but
did not significantly reduce viability following a 48 h exposure. ML
significantly reduced mRNA expression of mTOR and HIF-1alpha, while PG
significantly reduced mRNA of IGF-1R, AKT, mTOR and HIF-1alpha. ML and PG reduced
total protein expression of IGF-1R, IR, AKT, mTOR, and P70S6K. In addition, PG
reduced IRS protein. Both treatments also had an effect on phosphorylated protein
levels, with PG significantly reducing IGF-1R, AKT, and P70S6K levels. ML had a
similar effect and significantly decreased IR, AKT, and P70S6K phosphorylation
levels. Within the low concentration-range, ML and PG did not interact with the
cytotoxic activities of 5-FU. Overall, the AKT/mTOR signaling axis appears to be
implicated as causal in decreased proliferation induced by diet-relevant
concentrations of ML and PG.
PMID- 27491892
TI - Genomic identification, rapid evolution, and expression of Argonaute genes in the
tilapia, Oreochromis niloticus.
AB - Argonaute proteins are key components of the small RNA-induced silencing complex
and have multiple roles in RNA-directed regulatory pathways. Argonaute genes can
be divided into two subfamilies: the Ago (interacting with microRNA/small
interfering RNA) and Piwi subfamilies (interacting with piwi-interacting RNAs
(piRNAs)). In the present study, genome-wide analyses firstly yielded the
identification of different members of Agos and Piwis in the tilapia, coelacanth,
spotted gar, and elephant shark. The additional teleost Ago3b was generated
following the fish-specific genome duplication event. Selective pressure analysis
on Agos and Piwis between cichlids and other teleosts showed an accelerated
evolution of Piwil1 in the cichlid lineages, and the positive selected sites were
located in the region of PIWI domain, suggesting that these amino acid
substitutions are adapt to targeted cleavage of messenger RNA (mRNA) in cichlids.
Ago1 and Ago4 were detected at higher levels at 5 days after hatching (dah) in
both ovaries and testes compared with other stages, supporting the previously
reported requirement of Ago-mediated pathways to clear the maternal mRNAs during
the early embryogenesis. The Piwis were abundantly expressed in tilapia testes,
indicating their essential roles in male germline, especially in spermatogenesis.
Notable expression of Piwis was also detected in skeletal muscle, indicating that
piRNA pathway may not only be confined to development and maintenance of the
germline but may also play important roles in somatic tissues. The expression of
Piwil1 and Piwil2 was examined by quantitative PCR (qPCR) and in situ
hybridization (ISH) to validate the spatial and temporal expression profiles.
Taken together, these results present a thorough overview of tilapia Argonaute
family and provide a new perspective on the evolution and function of this family
in teleosts.
PMID- 27491894
TI - Optimal modified tracking performance for networked control systems with QoS
constraint.
AB - This paper investigates the optimal modified tracking performance of networked
control systems with a constraint on quality of service (QoS). The QoS is
characterized by two parameters of the system, viz. data dropout and the additive
white Gaussian noise. The proposed modified tracking performance index prevents
the probability of invalid data arising from the variations in the tracking error
in the absence of an integrator in the plant. The derived optimal filter
eliminates the influence of channel noise in the feedback channel. The optimal
modified tracking performance expression is obtained by using the co-prime
factorization. Results indicate that the optimal modified tracking performance is
influenced by the non-minimum phase zeros, modification factor, packet dropout
probability, and the characteristics of the reference signals. The obtained
results will give some guidance for the design of networked control systems. The
efficiency of the model is verified using some typical examples.
PMID- 27491893
TI - Concurrent quantification of multiple biomarkers indicative of oxidative stress
status using liquid chromatography-tandem mass spectrometry.
AB - 8-Hydroxy-2-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 8-iso
prostaglandin F2alpha (8-IsoPGF2alpha), and N-acetyl-S-(tetrahydro-5-hydroxy-2
pentyl-3-furanyl)-L-cysteine (HNE-MA) are well-studied and representative
biomarkers for oxidative DNA damage, inflammation, and lipid peroxidation; all of
which have been associated with increases in risks of various diseases and
cancers. A rapid and highly sensitive isotope-dilution liquid-chromatography
tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously
quantify the aforementioned biomarkers in urine. Upon validation, this method
shows excellent feasibility, sensitivity (0.008-0.03 ng/mL) and satisfactory
recoveries (88.7-95.4%); the calibration curves displayed excellent linearity
with coefficients of determination (R(2)) greater than 0.998. Additionally, low
variations were observed in the relative standard deviation for intra- and inter
day measurements for the four analytes. The relative matrix effects for all four
analytes ranged from 2.04 to 3.27%, which signaled that interferences from
endogenous levels of the analytes were deemed statistically insignificant. This
study successfully developed an analytical method capable to simultaneously
quantify urinary 8-OHdG, 8-NO2Gua, 8-IsoPGF2alpha, and HNE-MA. This analytical
protocol can be applied towards conducting epidemiological studies to reveal the
mechanisms related to disease development, and thus evaluate the associated risks
of diseases.
PMID- 27491895
TI - Meta-analysis of variance: an illustration comparing the effects of two dietary
interventions on variability in weight.
AB - Meta-analysis, which drives evidence-based practice, typically focuses on the
average response of subjects to a treatment. For instance in nutritional research
the difference in average weight of participants on different diets is typically
used to draw conclusions about the relative efficacy of interventions. As a
result of their focus on the mean, meta-analyses largely overlook the effects of
treatments on inter-subject variability. Recent tools from the study of
biological evolution, where inter-individual variability is one of the key
ingredients for evolution by natural selection, now allow us to study inter
subject variability using established meta-analytic models. Here we use meta
analysis to study how low carbohydrate (LC) ad libitum diets and calorie
restricted diets affect variance in mass. We find that LC ad libitum diets may
have a more variable outcome than diets that prescribe a reduced calorie intake.
Our results suggest that whilst LC diets are effective in a large proportion of
the population, for a subset of individuals, calorie restricted diets may be more
effective. There is evidence that LC ad libitum diets rely on appetite
suppression to drive weight loss. Extending this hypothesis, we suggest that
between-individual variability in protein appetite may drive the trends that we
report. A priori identification of an individual's target intake for protein may
help define the most effective dietary intervention to prescribe for weight loss.
PMID- 27491896
TI - Tunable electronic structures of germanium monochalcogenide nanosheets via light
non-metallic atom functionalization: a first-principles study.
AB - Germanium monochalcogenides, i.e. GeS and GeSe sheets, are isoelectronic
analogues of phosphorene, which have been synthesized in recent experiments (P.
Ramasamy et al., J. Mater. Chem. C, 2016, 4, 479). Utilizing first-principles
calculations, we have investigated their tunable electronic and magnetic
properties via light non-metallic atom (B, C, N, O, Si, P, S) functionalization.
We find that on these GeS and GeSe sheets O and S adatoms prefer to locate at the
top site above the Ge atom, while the other ones like to occupy the anion site,
which push the original S/Se atom to the hollow site instead. O and S adatoms
slightly affect the semiconducting behaviour of the doped systems, while B, C, N,
Si, P ones will drastically modify their band structures and induce versatile
spintronic properties. Through the supercell calculations, B and C adatoms are
found to induce a bipolar semiconducting behaviour in the decorated systems,
while the N/P adatom will cause a spin-gapless-semiconducting/nearly-half
metallic feature in them. The B/C/N/Si/P-substituted GeS/GeSe sheet can be formed
by removing the hollow-site S/Se atom from the adatom-decorated structures, which
exhibit an opposite semiconducting/metallic behaviour to their phosphorene
counterparts. A general odd-even rule is proposed for this phenomenon, which
shows that an odd (even) number of valence electron difference between the
substitution and host atoms would cause a metallic (semiconducting) feature in
the substituted systems. Our study demonstrates that atom functionalization is an
efficient way to tailor the properties of GeS and GeSe nanosheets, which have
adaptable electronic properties for potential applications in nanoelectronics and
spintronics.
PMID- 27491897
TI - Targeting Oxidative Stress in Central Nervous System Disorders.
AB - There is widespread recognition that reactive oxygen species (ROS) play key roles
in normal brain function and pathology in the context of neurological disease.
Oxidative stress continues to be a key therapeutic target for neurological
diseases. In developing antioxidant therapies for neurological disease, special
attention should be given to the brain's unique vulnerability to oxidative
insults and its architecture. Consideration of antioxidant therapy should be
guided by a strong rationale for oxidative stress in a given neurological
disease. This review provides an overview of processes that can guide the
development of antioxidant therapies in neurological diseases, such as knowledge
of basic redox mechanisms, unique features of brain pathophysiology, mechanisms
and classes of antioxidants, and desirable properties of drug candidates.
PMID- 27491898
TI - The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is
Associated with Anti-PD-1 Response in Patients with Renal Cell Carcinoma.
AB - Pretreatment tumor PD-L1 expression has been shown to correlate with response to
anti-PD-1/PD-L1 therapies. Yet, most patients with PD-L1(+) tumors do not respond
to treatment. The current study was undertaken to investigate mechanisms
underlying the failure of PD-1-targeted therapies in patients with advanced renal
cell carcinoma (RCC) whose tumors express PD-L1. Formalin-fixed, paraffin
embedded pretreatment tumor biopsies expressing PD-L1 were derived from 13 RCC
patients. RNA was isolated from PD-L1(+) regions and subjected to whole genome
microarray and multiplex quantitative (q)RT-PCR gene expression analysis. A
balance between gene expression profiles reflecting metabolic pathways and immune
functions was associated with clinical outcomes following anti-PD-1 therapy. In
particular, the expression of genes involved in metabolic and solute transport
functions such as UGT1A family members, also found in kidney cancer cell lines,
was associated with treatment failure in patients with PD-L1(+) RCC. Conversely,
tumors from responding patients overexpressed immune markers such as BACH2, a
regulator of CD4(+) T-cell differentiation, and CCL3 involved in leukocyte
migration. These findings suggest that tumor cell-intrinsic metabolic factors may
contribute to treatment resistance in RCC, thus serving as predictive markers for
treatment outcomes and potential new targets for combination therapy regimens
with anti-PD-1. Cancer Immunol Res; 4(9); 726-33. (c)2016 AACRSee related
Spotlight by Ohashi, p. 719.
PMID- 27491899
TI - Retroviral particles are effectively purified on an affinity matrix containing
peptides selected by phage-display.
AB - Retroviral particles are expensive to manufacture, mostly due to the downstream
processing steps which result in low recoveries (~30%) and concentration factors.
In this work, a dodecapeptide phage-display library was panned against retrovirus
like particles expressing the envelope protein Ampho4070A (VLPs-AMPHO) and VLPs
without the target protein, used as a negative control (VLPs). A
depletion/selection panning protocol was successfully used to deal with the
structural complexity of the target, and a total of three distinct peptide
sequences displaying preferential binding towards VLPs-AMPHO were found. Peptide
3 (CAAALAKPHTENHLLT), which appeared as one lead candidate, was synthesized and
immobilized onto two purification matrices, cross-linked agarose and magnetic
particles. The matrices selectively bound VLPs-AMPHO and in both cases recovery
yields higher than 90% were obtained when employing mild elution conditions,
while maintaining viral particle morphology and size.
PMID- 27491900
TI - Cardiovascular Magnetic Resonance to Evaluate Aortic Regurgitation After
Transcatheter Aortic Valve Replacement.
AB - BACKGROUND: Residual aortic regurgitation (AR) following transcatheter aortic
valve replacement (TAVR) is associated with greater mortality; yet, determining
AR severity post-TAVR using Doppler echocardiography remains challenging.
Cardiovascular magnetic resonance (CMR) is purported as a more accurate means of
quantifying AR; however, no data exist regarding the prognostic value of AR as
assessed by CMR post-TAVR. OBJECTIVES: This study sought to evaluate the effect
of AR assessed with CMR on clinical outcomes post-TAVR. METHODS: We included 135
patients from 3 centers. AR was quantified using regurgitant fraction (RF)
measured by phase-contrast velocity mapping CMR at a median of 40 days post-TAVR,
and using Doppler echocardiography at a median of 6 days post-TAVR. Median follow
up was 26 months. Clinical outcomes included mortality and rehospitalization for
heart failure. RESULTS: Moderate-severe AR occurred in 17.1% and 12.8% of
patients as measured by echocardiography and CMR, respectively. Higher RF post
TAVR was associated with increased mortality (hazard ratio: 1.18 for each 5%
increase in RF [95% confidence interval: 1.08 to 1.30]; p < 0.001) and the
combined endpoint of mortality and rehospitalization for heart failure (hazard
ratio: 1.19 for each 5% increase in RF; 95% confidence interval: 1.15 to 1.23; p
< 0.001). Prediction models yielded significant incremental predictive value; CMR
performed a median of 40 days post-TAVR had a greater association with post-TAVR
clinical events compared with early echocardiography (p < 0.01). RF >=30% best
predicted poorer clinical outcomes (p < 0.001 for either mortality or the
combined endpoint of mortality and heart failure rehospitalization). CONCLUSIONS:
Worse CMR-quantified AR was associated with increased mortality and poorer
clinical outcomes following TAVR. Quantifying AR with CMR may identify patients
with AR who could benefit from additional treatment measures.
PMID- 27491901
TI - When Accurate Flow Quantitation Matters: The Case of CMR Assessment of Aortic
Regurgitation After TAVR.
PMID- 27491902
TI - Cerebral Embolism: A Silent Iatrogenic Complication of TAVR That Needs Voiced
Consideration.
PMID- 27491903
TI - Radial Artery as a Coronary Artery Bypass Conduit: 20-Year Results.
AB - BACKGROUND: There is a lack of evidence for the choice of the second conduit in
coronary surgery. The radial artery (RA) is a possible option, but few data on
very-long-term outcomes exist. OBJECTIVES: This study describes 20-year results
of RA grafts used for coronary artery bypass grafting and the effects of RA
removal on forearm circulation. METHODS: We report the results of the prospective
20-year follow-up of the first 100 consecutive patients who received the RA as a
coronary bypass conduit at our institution. RESULTS: Follow-up was 100% complete.
There were 64 deaths, 23 (35.9%) from cardiovascular causes. Kaplan-Meier 20-year
survival was 31%. Of the 36 survivors, 33 (91.6%) underwent RA graft control at a
mean of 19.0 +/- 2.5 years after surgery. The RA was found to be patent in 24
cases (84.8% patency). In the overall population, probability of graft failure at
20 years was 19.0 +/- 0.2% for the left internal thoracic artery (ITA), 25.0 +/-
0.2% for the RA, and 55.0 +/- 0.2% for the saphenous vein (p = 0.002 for RA vs.
saphenous vein, 0.11 for RA vs. ITA, and p < 0.001 for ITA vs. saphenous vein).
Target vessel stenosis >90%, but not location of distal anastomosis,
significantly influenced long-term RA graft patency. No patients reported hand or
forearm symptoms. The ulnar artery diameter was increased in the operated arm
(2.44 +/- 0.43 mm vs. 2.01 +/- 0.47 mm; p < 0.05) and correlated with the peak
systolic velocity of the second palmar digital artery (Pearson coefficient:
0.621; p < 0.05). CONCLUSIONS: The 20-year patency rate of RA grafts is good, and
not inferior to the ITA, especially when the conduit is used to graft a vessel
with >90% stenosis. RA harvesting does not lead to hand or forearm symptoms, even
at a very-long-term follow-up.
PMID- 27491904
TI - The Radial Artery Graft: Clinical or Subclinical Benefits?
PMID- 27491905
TI - Long-Term Trends in Newly Diagnosed Brugada Syndrome: Implications for Risk
Stratification.
AB - BACKGROUND: A proband of Brugada syndrome (BrS) is the first patient diagnosed in
a family. There are no data regarding this specific, high-risk population.
OBJECTIVES: This study sought to investigate the Brugada probands diagnosed from
1986 through the next 28 years. METHODS: We included 447 probands belonging to
families with a diagnostic type 1 electrocardiogram Brugada pattern. The database
was divided into 2 periods: the first period identified patients who were part of
the initial cohort that became the consensus document on BrS in 2002 (early
group); the second period reflected patients first diagnosed from 2003 to January
2014 (latter group). RESULTS: There were 165 probands in the early group and 282
in the latter group. Aborted sudden death as the first manifestation of the
disease occurred in 12.1% of the early group versus 4.6% of the latter group (p =
0.005). Inducibility during programmed electrical stimulation was achieved in
34.4% and 19.2% of patients, respectively (p < 0.001). A spontaneous type 1
electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2%
latter patients (p = 0.0002). Early group patients had a higher probability of a
recurrent arrhythmia during follow-up (19%) than those of the latter group (5%)
(p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask
BrS has allowed earlier diagnoses in many patients. CONCLUSIONS: Since being
first described, the presentation of BrS has changed. There has been a decrease
in aborted sudden cardiac death as the first manifestation of the disease among
patients who were more recently diagnosed. These variations in initial
presentation have important clinical consequences. In this setting, the value of
inducibility to stratify individuals with BrS has changed.
PMID- 27491906
TI - Brugada Syndrome: The Endless Conundrum.
PMID- 27491907
TI - Predicting In-Hospital Mortality in Patients With Acute Myocardial Infarction.
AB - BACKGROUND: As a foundation for quality improvement, assessing clinical outcomes
across hospitals requires appropriate risk adjustment to account for differences
in patient case mix, including presentation after cardiac arrest. OBJECTIVES: The
aim of this study was to develop and validate a parsimonious patient-level
clinical risk model of in-hospital mortality for contemporary patients with acute
myocardial infarction. METHODS: Patient characteristics at the time of
presentation in the ACTION (Acute Coronary Treatment and Intervention Outcomes
Network) Registry-GWTG (Get With the Guidelines) database from January 2012
through December 2013 were used to develop a multivariate hierarchical logistic
regression model predicting in-hospital mortality. The population (243,440
patients from 655 hospitals) was divided into a 60% sample for model derivation,
with the remaining 40% used for model validation. A simplified risk score was
created to enable prospective risk stratification in clinical care. RESULTS: The
in-hospital mortality rate was 4.6%. Age, heart rate, systolic blood pressure,
presentation after cardiac arrest, presentation in cardiogenic shock,
presentation in heart failure, presentation with ST-segment elevation myocardial
infarction, creatinine clearance, and troponin ratio were all independently
associated with in-hospital mortality. The C statistic was 0.88, with good
calibration. The model performed well in subgroups based on age; sex; race;
transfer status; and the presence of diabetes mellitus, renal dysfunction,
cardiac arrest, cardiogenic shock, and ST-segment elevation myocardial
infarction. Observed mortality rates varied substantially across risk groups,
ranging from 0.4% in the lowest risk group (score <30) to 49.5% in the highest
risk group (score >59). CONCLUSIONS: This parsimonious risk model for in-hospital
mortality is a valid instrument for risk adjustment and risk stratification in
contemporary patients with acute myocardial infarction.
PMID- 27491908
TI - No One Size Fits All: Scoring Risk of In-Hospital Death After Myocardial
Infarction.
PMID- 27491909
TI - A Test in Context: Neprilysin: Function, Inhibition, and Biomarker.
AB - Neprilysin is a zinc-dependent endopeptidase. It is ubiquitous in distribution
and promiscuous in function, with >50 putative peptide substrates with varying
levels of in vitro and/or in vivo evidence of functional relevance. In the first
part of this review, we discuss the genetic, structural, substrate, and
pathophysiological aspects of neprilysin. We incorporate information provided by
genetically modified models, as well as pre-clinical and clinical data from
investigations of synthetic neprilysin inhibitors. We next highlight the value of
neprilysin as a biotarget and weigh the clinical benefits of synthetic neprilysin
inhibitors, either alone or in combination with antagonists of the renin
angiotensin system. Finally, we provide evidence about soluble neprilysin as a
biomarker surrogate in patients with heart failure and identify important gaps
that require further research before soluble neprilysin is used clinically. In
sum, neprilysin is a versatile, veteran player returning yet again to center
stage after an eventful career spanning >40 years.
PMID- 27491910
TI - Aortic Valve Sparing in Different Aortic Valve and Aortic Root Conditions.
AB - The development of aortic valve-sparing operations (reimplantation of the aortic
valve and remodeling of the aortic root) expanded the surgical armamentarium for
treating patients with aortic root dilation caused by a variety of disorders.
Young adults with aortic root aneurysms associated with genetic syndromes are
ideal candidates for reimplantation of the aortic valve, and the long-term
results have been excellent. Incompetent bicuspid aortic valves with dilated
aortic annuli are also satisfactorily treated with the same type of operation.
Older patients with ascending aortic aneurysm and aortic insufficiency secondary
to dilated sinotubular junction and a normal aortic annulus can be treated with
remodeling of the aortic root or with reimplantation of the aortic valve. The
first procedure is simpler, and both procedures are likely equally effective. As
with any heart valve-preserving procedure, patient selection and surgical
expertise are keys to successful and durable repairs.
PMID- 27491911
TI - Brugada Syndrome and the Subcutaneous Implantable Cardioverter-Defibrillator.
PMID- 27491912
TI - Community-Based Trends in Acute Myocardial Infarction From 2008 to 2014.
PMID- 27491913
TI - Mean Arterial Pressure Estimation by a Non-Traditional Formula and Fractional
Pulse Pressure.
PMID- 27491914
TI - Reply: Mean Arterial Pressure Estimation by a Non-Traditional Formula and
Fractional Pulse Pressure.
PMID- 27491915
TI - A Prima Vista Ablation of Ventricular Tachycardia: Should We Abandon the Mapping
of VT?
PMID- 27491916
TI - Reply: A Prima Vista Ablation of Ventricular Tachycardia: Should We Abandon the
Mapping of VT?
PMID- 27491917
TI - Small angle x-ray scattering with edge-illumination.
AB - Sensitivity to sub-pixel sample features has been demonstrated as a valuable
capability of phase contrast x-ray imaging. Here, we report on a method to obtain
angular-resolved small angle x-ray scattering distributions with edge
illumination- based imaging utilizing incoherent illumination from an x-ray tube.
Our approach provides both the three established image modalities (absorption,
differential phase and scatter strength), plus a number of additional contrasts
related to unresolved sample features. The complementarity of these contrasts is
experimentally validated by using different materials in powder form. As a
significant application example we show that the extended complementary contrasts
could allow the diagnosis of pulmonary emphysema in a murine model. In support of
this, we demonstrate that the properties of the retrieved scattering
distributions are consistent with the expectation of increased feature sizes
related to pulmonary emphysema. Combined with the simplicity of implementation of
edge-illumination, these findings suggest a high potential for exploiting
extended sub-pixel contrasts in the diagnosis of lung diseases and beyond.
PMID- 27491918
TI - CNS Multiparameter Optimization Approach: Is it in Accordance with Occam's Razor
Principle?
AB - A detailed analysis of the possibility of using the Multiparameter Optimization
approach (MPO) for CNS/non-CNS classification of drugs was carried out. This work
has shown that MPO descriptors are able to describe only part of chemical
transport in the CNS connected with transmembrane diffusion. Hence the
"intuitive" CNS MPO approach with arbitrary selection of descriptors and
calculations of score functions, search of thresholds of classification, and
absence of any chemometric procedures, leads to rather modest accuracy of CNS/non
CNS classification models.
PMID- 27491919
TI - 3D Structure, Dimerization Modeling, and Lead Discovery by Ligand-protein
Interaction Analysis of p60 Transcription Regulator Protein (p60TRP).
AB - The p60 transcription regulator protein (p60TRP) is a basic helix-loop-helix
(bHLH) domain-containing neuroprotective protein and a member of the G-protein
coupled receptor (GPCR)-associated sorting protein (GPRASP) family. In the
present study, multiple theoretical physico-chemical methods (e.g. Modeller
v.9.13, I-TASSER, PROCHECK and ClusPro v2.0 with PIPER) were applied to unveil
the three-dimensional (3D) protein structure of the p60TRP homo-dimer protein and
explore potential ligand-protein interactions. Our results suggest a Mg(2+)
containing 3D p60TRP dimer protein that potentially interacts with 5-(1
aziridinyl)-2,4-dinitrobenzamide (CB1954) and [2-(3-dodecylimidazolidin-1-yl)-1
phosphonoethyl] phosphonic acid (B73). The discovery of CB1954 and B73 may serve
as a potential lead for further drug screening tests to normalize the p60TRP
signaling pathway in neurodegenerative diseases. Interference with p60TRP
signaling via CB1954/B73-related molecules might be a novel option for modifying
neurodegenerative signaling pathways (e.g. RIN1, PP2A, RanBP5, CREB and SYNJ1) to
treat various brain diseases.
PMID- 27491920
TI - Classification of Mixtures of Chinese Herbal Medicines Based on a Self-organizing
Map (SOM).
AB - Chinese Herbal Medicines (CHMs) are typically mixtures of compounds and are often
categorized into cold and hot according to the theory of Chinese Medicine. This
classification is essential for guiding the clinical application of CHMs. In this
study, three types of molecular descriptors were used to build models for
classification of 59 CHMs with typical cold/hot properties in the training set
taken from the original records on properties in China Pharmacopeia as reference.
The accuracy and the Matthews correlation coefficient of the models were
validated by a test set containing other 56 CHMs. The best model produced the
accuracies of 94.92 % and 83.93 % on training set and test set, respectively. The
MACCS fingerprint model is robust in predicting hot/cold properties of the CHMs
from their major constituting compounds. This work shows how a classification
model for data consisting of multi-components can be developed. The derived model
can be used for the application of Chinese herbal medicines.
PMID- 27491921
TI - Using Support Vector Machine (SVM) for Classification of Selectivity of H1N1
Neuraminidase Inhibitors.
AB - Inhibition of the neuraminidase is one of the most promising strategies for
preventing influenza virus spreading. 479 neuraminidase inhibitors are collected
for dataset 1 and 208 neuraminidase inhibitors for A/P/8/34 are collected for
dataset 2. Using support vector machine (SVM), four computational models were
built to predict whether a compound is an active or weakly active inhibitor of
neuraminidase. Each compound is represented by MASSC fingerprints and
ADRIANA.Code descriptors. The predication accuracies for the test sets of all the
models are over 78 %. Model 2B, which is the best model, obtains a prediction
accuracy and a Matthews Correlation Coefficient (MCC) of 89.71 % and 0.81 on test
set, respectively. The molecular polarizability, molecular shape, molecular size
and hydrogen bonding are related to the activities of neuraminidase inhibitors.
The models can be obtained from the authors.
PMID- 27491922
TI - A Random Forest Model for Predicting Allosteric and Functional Sites on Proteins.
AB - We created a computational method to identify allosteric sites using a machine
learning method trained and tested on protein structures containing bound ligand
molecules. The Random Forest machine learning approach was adopted to build our
three-way predictive model. Based on descriptors collated for each ligand and
binding site, the classification model allows us to assign protein cavities as
allosteric, regular or orthosteric, and hence to identify allosteric sites. 43
structural descriptors per complex were derived and were used to characterize
individual protein-ligand binding sites belonging to the three classes,
allosteric, regular and orthosteric. We carried out a separate validation on a
further unseen set of protein structures containing the ligand 2-(N
cyclohexylamino) ethane sulfonic acid (CHES).
PMID- 27491923
TI - In silico Prediction of Drug Induced Liver Toxicity Using Substructure Pattern
Recognition Method.
AB - Drug-induced liver injury (DILI) is a leading cause of acute liver failure in the
US and less severe liver injury worldwide. It is also one of the major reasons of
drug withdrawal from the market. Thus, DILI has become one of the most important
concerns of drugs, and should be predicted in very early stage of drug discovery
process. In this study, a comprehensive data set containing 1317 diverse
compounds was collected from publications. Then, high accuracy classification
models were built using five machine learning methods based on MACCS and FP4
fingerprints after evaluating by substructure pattern recognition method. The
best model was built using SVM method together with FP4 fingerprint at the IG
value threshold of 0.0005. Its overall predictive accuracies were 79.7 % and 64.5
% for the training and test sets, separately, which yielded overall accuracy of
75.0 % for the external validation dataset, consisting of 88 compounds collected
from a benchmark DILI database - the Liver Toxicity Knowledge Base. This model
could be used for drug-induced liver toxicity prediction. Moreover, some key
substructure patterns correlated with drug-induced liver toxicity were also
identified as structural alerts.
PMID- 27491924
TI - Structural and Functional Diversities of the Hexadecahydro-1H
cyclopenta[a]phenanthrene Framework, a Ubiquitous Scaffold in Steroidal Hormones.
AB - Hexadecahydro-1H-cyclopenta[a]phenanthrene framework (HHCPF) has been considered
as one of the privileged scaffolds due to its versatile presence in many
biologically essential molecules. In our quest to unravel the privileged nature
of this framework, we undertook a systematic analysis of target binding and
Absorption, Distribution, Metabolism, Elimination, Toxicity
(ADMET)/physicochemical properties of 110 drugs containing HHCPF reported in
DrugBank. Effect of number and positions of double bonds in the framework and
substitutions at each carbon position on the target selectivity as well as drug
like properties of these drugs were studied. Fifteen different scaffolds based on
the numbers and positions of double bonds in the HHCPF were identified among
these drugs. The optimum number of double bonds present in the HHCPF scaffolds
was observed to be one to three, and one particular positional isomer is
predominant among many scaffolds with same numbers of double bonds. Docking
studies reveal the role of substituents at different positions to make specific
interactions with their respective targets. Based on the docking interactions, we
proposed structure based e-Pharmacophore models for seven important targets of
HHCPF drugs. Good correlations were observed between the substitutions carbon
positions 3 and 17 of the scaffolds and ADMET properties of the HHCPF drugs. This
work enables preliminary prediction of the target selectivity and ADMET
properties of a new HHCPF molecule based on the scaffold, substituents and the
pharmacophoric features.
PMID- 27491925
TI - Microbiomic and Posttranslational Modifications as Preludes to Autoimmune
Diseases.
AB - Diagnosis and treatment of autoimmunity has mainly relied on adaptive immunity.
Infection and inflammation induce cytokines and chemokines and activate myeloid
cells to release enzymes. Proteases cleave host proteins into a molar excess of
remnant peptides. Additional enzymes modify these peptides into putative
autoantigens prior to T and B cell activation. We propose that post-translational
modifications may be a means of generating auto-reactive peptides. Microbes also
provide proteases and modifying enzymes to the host, and we posit that this may
result in autoantigen generation. This could help explain, at least in part, the
recently discovered connections between microbiota and autoimmunity. Better
explorations of the innate prelude phase of autoimmunity in conjunction with
environmental factors might provide novel, broadly applicable therapies.
PMID- 27491927
TI - Hierarchical architecture of the inner layers of selected extant rhynchonelliform
brachiopods.
AB - In spite of several attempts for a best knowledge of the phylum, brachiopods
remain, compared with molluscs, among those least analysed in terms of
biomineralization. The lack of economic impact for extant species is probably
liable for that situation. Much attention has been on the microstructure of
calcite biomaterials (rhynchonelliforms and craniiforms). Here, we emphasize the
sub-micrometric structure of selected examples of rhynchonelliform shells using
Atomic Force Microscopy (AFM) to complement Scanning Electron Microscopy (SEM)
and Energy Dispersive X-ray (EDX) analyses. The hierarchical organization of the
shell layers (secondary and/or tertiary elements) is highlighted for species non
yet observed from this point of view, and is compared to a few already mentioned
in the literature. Previous analysis revealed that granules are composed of a
complex aggregation of sub-units in intimate relation with an intracrystalline
matrix. Their shape, size and probably early orientation depend on the species as
well as age and living environments of the specimens studied. The control of the
inorganic part of the composite fibrous elements is constrained by the deposition
of nearly arched shape or polygonal protein membranes at the inner boundary of
the primary layer, prior to the deposition of the first granules, membranes
becoming proteinaceous sheathes progressively enshrining fibres. The diverse
orientations of the granules in fibrous neighbours thus further increase
arguments in favour of the tendency to improve the shell strength.
PMID- 27491928
TI - Allergen-specific immune response suppresses interleukin 10 expression in B cells
via increasing micro-RNA-17-92 cluster.
AB - Interleukin (IL)-10-expressing B cells play a critical role in the immune
homeostasis in the body; its regulation has not been fully understood. Micro-RNA
(miR)-17-92 cluster has strong regulation in the immunity. This study tests a
hypothesis that miR-17-92 cluster suppresses IL-10 expression in B cells. In this
study, peripheral B cells were collected from patients with allergic rhinitis
(AR). The B cells were treated with specific allergens, dust mite extracts, in
the culture. The expressions of miR-17-92 cluster and IL-10 in the culture were
assessed by real-time quantitative reverse transcription polymerase chain
reaction and enzyme-linked immunosorbent assay. The results showed that the
levels of miR-19a, but not the rest of the 5 members (miR-17, miR-18a, miR-19b,
miR-20a, and miR-92a), were significantly higher in peripheral B cells from AR
patients as than in B cells from healthy participants. Exposure of B cells from
AR patients to specific allergen, dust mite extracts, significantly increased the
levels if miR-19a and suppressed the expression of IL-10 in B cells. The levels
of histone deacetylase 11 and acetylated H3K9 were higher, and the RNA polymerase
II and c-Maf (the IL-10 transcription factor) were lower, at the IL-10 promoter
locus. In conclusion, miR-19a mediates the allergen-specific immune response
decreased IL-10 expression in B cells.
PMID- 27491929
TI - A Mathematical Model for Biocontrol of the Invasive Weed Fallopia japonica.
AB - We propose a mathematical model for biocontrol of the invasive weed Fallopia
japonica using one of its co-evolved natural enemies, the Japanese sap-sucking
psyllid Aphalara itadori. This insect sucks the sap from the stems of the plant
thereby weakening it. Its diet is highly specific to F. japonica. We consider a
single isolated knotweed stand, the plant's size being described by time
dependent variables for total stem and rhizome biomass. It is the larvae of A.
itadori that damage the plant most, so the insect population is described in
terms of variables for the numbers of larvae and adults, using a stage-structured
modelling approach. The dynamics of the model depends mainly on a parameter h,
which measures how long it takes for an insect to handle (digest) one unit of F.
japonica stem biomass. If h is too large, then the model does not have a positive
equilibrium and the plant biomass and insect numbers both grow together without
bound, though at a lower rate than if the insects were absent. If h is
sufficiently small, then the model possesses a positive equilibrium which appears
to be locally stable. The results based on our model imply that satisfactory long
term control of the knotweed F. japonica using the insect A. itadori is only
possible if the insect is able to consume and digest knotweed biomass
sufficiently quickly; if it cannot, then the insect can only slow down the growth
which is still unbounded.
PMID- 27491930
TI - Letter in response to "Efficacy and effectiveness of anti-digoxin antibodies in
chronic digoxin poisonings from the DORA study (ATOM-1)".
PMID- 27491926
TI - Phage-Enabled Nanomedicine: From Probes to Therapeutics in Precision Medicine.
AB - Both lytic and temperate bacteriophages (phages) can be applied in nanomedicine,
in particular, as nanoprobes for precise disease diagnosis and nanotherapeutics
for targeted disease treatment. Since phages are bacteria-specific viruses, they
do not naturally infect eukaryotic cells and are not toxic to them. They can be
genetically engineered to target nanoparticles, cells, tissues, and organs, and
can also be modified with functional abiotic nanomaterials for disease diagnosis
and treatment. This Review will summarize the current use of phage structures in
many aspects of precision nanomedicine, including ultrasensitive biomarker
detection, enhanced bioimaging for disease diagnosis, targeted drug and gene
delivery, directed stem cell differentiation, accelerated tissue formation,
effective vaccination, and nanotherapeutics for targeted disease treatment. We
will also propose future directions in the area of phage-based nanomedicines, and
discuss the state of phage-based clinical trials.
PMID- 27491932
TI - Hereditary angioedema: death after a dental extraction.
AB - Hereditary angioedema (HAE) is a group of three uncommon and potentially fatal
conditions, each of which is transmitted as a somatic dominant trait. A
recognized trigger to attacks is dental treatment, with tooth extraction
frequently reported in the published work. The clinical symptoms may not manifest
for many hours or even days after the procedure. We describe a recent case in
Australia in which death resulted from HAE following dental extraction, and we
discuss its post-mortem presentation and diagnosis, highlighting the need for
dental practitioners to be aware of this condition.
PMID- 27491933
TI - Impact of glyphosate-resistant corn, glyphosate applications and tillage on soil
nutrient ratios, exoenzyme activities and nutrient acquisition ratios.
AB - BACKGROUND: We report results of the last two years of a 7 year field experiment
designed to test the null hypothesis: applications of glyphosate on glyphosate
resistant (GR) and non-resistant (non-GR) corn (Zea mays L.) under conventional
tillage and no-till would have no effect on soil exoenzymes and microbial
activity. RESULTS: Bulk soil (BS) and rhizosphere soil (RS) macronutrient ratios
were not affected by either GR or non-GR corn, or glyphosate applications.
Differences observed between exoenzyme activities were associated with tillage
rather than glyphosate applications. In 2013, nutrient acquisition ratios for
bulk and rhizosphere soils indicated P limitations, but sufficient assimilable N.
In 2014, P limitations were observed for bulk and rhizosphere soils, in contrast
to balanced C and N acquisition ratios in rhizosphere soils. Stoichiometric
relationships indicated few differences between glyphosate and non-glyphosate
treatments. Negative correlations between C:P and N:P nutrient ratios and
nutrient acquisition ratios underscored the inverse relation between soil
nutrient status and microbial community exoenzyme activities. CONCLUSIONS:
Inconsistent relationships between microbial community metabolic activity and
exoenzyme activity indicated an ephemeral effect of glyphosate on BS exoenzyme
activity. Except for ephemeral effects, glyphosate applications appeared not to
affect the function of the BS and RS exoenzymes under conventional tillage or no
till. Published 2016. This article is a U.S. Government work and is in the public
domain in the USA.
PMID- 27491931
TI - Edible Ginger-derived Nano-lipids Loaded with Doxorubicin as a Novel Drug
delivery Approach for Colon Cancer Therapy.
AB - The use of nanotechnology for drug delivery has shown great promise for improving
cancer treatment. However, potential toxicity, hazardous environmental effects,
issues with large-scale production, and potential excessive costs are challenges
that confront their further clinical applications. Here, we describe a nanovector
made from ginger-derived lipids that can serve as a delivery platform for the
therapeutic agent doxorubicin (Dox) to treat colon cancer. We created
nanoparticles from ginger and reassembled their lipids into ginger-derived
nanovectors (GDNVs). A subsequent characterization showed that GDNVs were
efficiently taken up by colon cancer cells. Viability and apoptosis assays and
electric cell-substrate impedance-sensing technology revealed that GDNVs
exhibited excellent biocompatibility up to 200 MUmol/l; by contrast, cationic
liposomes at the same concentrations decreased cell proliferation and increased
apoptosis. GDNVs were capable of loading Dox with high efficiency and showed a
better pH-dependent drug-release profile than commercially available liposomal
Dox. Modified GDNVs conjugated with the targeting ligand folic acid mediated
targeted delivery of Dox to Colon-26 tumors in vivo and enhanced the
chemotherapeutic inhibition of tumor growth compared with free drug. Current
experiments explore the feasibility of producing nature-derived nanoparticles
that are effective as a treatment vehicle while potentially attenuating the
issues related to traditional synthetic nanoparticles.
PMID- 27491934
TI - A scoping review examining physical activity measurement and levels in the first
2 years of life.
AB - BACKGROUND: The first few years of life have been identified as a critical stage
in the development of activity behaviours, which have been shown to track into
later life. This scoping review aims to assess the literature reporting on
physical activity levels in the first 2 years of life in order to answer two main
questions: (i) how is physical activity measured in this age group? and (ii) how
active are infants and toddlers in the first 2 years of life? METHODS: A search
strategy was employed using PubMed with restrictions only on age and language.
After applying exclusion criteria, 20 papers were included in the results.
RESULTS: Seventeen studies used some form of objective assessment of physical
activity (accelerometers, actometers, direct observation, doubly labelled water
or a metabolic chamber); while the remaining three relied on subjective
assessments (parent reported questionnaires or interviews, and activity diaries).
Nine studies exclusively assessed infants (<12 months), and five exclusively
assessed toddlers (>12 months). Only six studies reported physical activity
levels and patterns specifically; most included studies measured activity as a
covariate or correlate. Therefore, much of the reported data was difficult to
assess, as results were vague or incompletely described. Where data were reported
sufficiently for analysis, results were equally conflicted regarding whether
toddlers were meeting recommended physical activity guidelines. CONCLUSIONS: This
scoping review re-iterates the fact that more studies need to be conducted, which
focus primarily on measuring and reporting physical activity levels and patterns
in this age group in a comprehensive and standardized way, so that more informed
guidelines can be devised and interventions can be designed and implemented where
necessary.
PMID- 27491935
TI - 9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-11H
indeno[1, 2-c]quinolin-11-one (BPIQ), A Quinoline Derivative Inhibits Human
Hepatocellular Carcinoma Cells by Inducing ER Stress and Apoptosis.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading cancers in the
world, including Taiwan. The chemoresistance of advanced HCC frequently results
in the poor prognosis of patients. Previous studies demonstrated the quinoline
derivative, 9-bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1
yl)ethoxy]phenyl}-11Hindeno[ 1,2-c]quinolin-11-one (BPIQ) exerts the inhibitory
potential against several cancer cells, including liver cancer cells. OBJECTIVE:
We further investigated the anti-HCC effects of BPIQ, including apoptosis and the
modulation of ER stress. METHODS: Both trypan blue exclusion assay and colony
formation assay were performed to examine whether BPIQ affects the growth of HCC
cell lines Ha22T and Huh7. Flow cytometry-based assay was performed for
determining the cell cycle distribution and apoptosis. Western blot assay was
conducted for detecting the changes in apoptosis- and endoplasmic reticulum (ER)
stress-associated proteins. RESULTS: BPIQ inhibits cell growth and induces the
apoptosis of both Ha22T and Huh7 cell lines significantly. The level of
gammaH2AX, an endogenous DNA damage biomarker was dramatically increased
suggesting the involvement of DNA damage pathway in BPIQ-induced apoptosis.
Further, BPIQ down-regulates the pro-survival proteins, survivin, XIAP and cyclin
D1. BPIQ also may regulate ER stress response through modulating the levels of ER
stress-related proteins Glucose-regulated protein of 78 kD (GRP78), Inositol
requiring kinase-1alpha (IREalpha), C/EBP homologous protein (Chop) and calnexin.
CONCLUSIONS: The anti-HCC effect of BPIQ may occur through down-regulating pro
survival proteins, and the modulation of ER stress may contribute to the BPIQ
induced apoptosis of HCC cells. The chemotherapeutic or chemopreventive
applications of BPIQ for HCC treatment will be worthy of further investigation in
future.
PMID- 27491937
TI - Synthesis and Evaluation of A New Series of Thiazole Derivatives as Potential
Antitumor Agents and MMP Inhibitors.
AB - BACKGROUND: In recent years, the relationship between overexpression of matrix
metalloproteinases (MMPs) and tumor invasion/metastasis has prompted researchers
to develop MMP inhibitors as anticancer drugs. OBJECTIVE: The aim of this study
was to design and synthesize new thiazole-based anticancer agents targeting MMPs.
METHOD: New thiazole derivatives were synthesized and investigated for their
cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast
adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using MTT assay.
The potential inhibitory effects of the best candidates on gelatinases (MMP-2,
MMP-9), and collagenases (MMP-1, MMP-8, MMP-13) were evaluated. RESULTS: Ethyl 2
[2-((4-amino-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl)thio)acetamido]-4
methylthiazole-5-carboxylate (3) was found to be the most promising anticancer
agent against MCF-7 cell line due to its selective inhibitory effect on MCF-7
cells with an IC50 value of 20.6+/-0.3 MUg/mL when compared with cisplatin (IC50=
35.31+/-0.51 MUg/mL). Compound 3 also showed multiple MMP (MMP-1, MMP-8 and MMP
9) inhibitory activity (10.56+/-1.70, 20 and 7.28+/-1.49%, respectively).
CONCLUSION: The notable anticancer activity and selectivity of compound 3 on MCF
7 cell line can be attributed to multiple MMP inhibition potential.
PMID- 27491938
TI - Postpartum Depression and Social Support in China: A Cultural Perspective.
AB - This study explored how Chinese culture affects the relationship between social
support and postpartum depression. In-depth interviews with 38 mothers in
mainland China showed that discrepancies between expected and perceived available
social support and conflicts among social support providers are two major
contributors to the stress associated with postpartum depression. These dynamics
are deeply rooted in the context of Chinese culture with its distinctive gender
roles and family dynamics. These cultural norms further prevent women from
seeking social support.
PMID- 27491936
TI - The Effects of 1,3,5-trisubstituted Indole Derivatives on Cell Growth, Apoptosis
and MMP-2/9 mRNA Expression of MCF-7 Human Breast Cancer Cells.
AB - BACKGROUND: Matrix metalloproteinases are known as extracellular matrix degrading
enzymes and have important role on tumor progression. OBJECTIVE: This study
reports the effects of 1,3,5-trisubstituted indole derivatives on cytotoxicity,
apoptosis and MMP- 2/MMP-9 mRNA expression of MCF-7 human breast carcinoma cells.
METHOD: The cytotoxic effects of the compounds on MCF-7 cells were performed by
MTT test, and cell proliferation was determined via BrdU incorporation. The
apoptotic effects were observed by cell death detection elisa. The effects of the
compounds on MMP-2/-9 enzyme activity and mRNA expression were also performed.
RESULTS: The compounds inhibited the proliferation of MCF-7 breast carcinoma
cells significantly in a dose dependent manner. All compounds were able to induce
DNA fragmentation, especially compound 1. The IC50 values of compound 2 and 4 for
MMP-2 were 0.42 MUM and 1.88 MUM, respectively. MMP-2 mRNA expression results
were correlated with the inhibition of enzyme activity, such compound 4 inhibited
MMP-2 mRNA expression at all treated concentrations. Docking simulation has also
been performed to analyze the binding mode of compounds and the results showed
that compound 2, the most active compound, formed a hydrogen bond with Glu202 for
binding to the MMP-2 active site. In addition, the hydrophobic parts of compound
2 are in contact with nonpolar surface areas of MMP-2, such as His201, His211,
Tyr223 and Tyr193. CONCLUSION: According to the molecular docking results along
with the biological assay data, it is suggested that compound 2 might be used for
further design and development of MMP-2 inhibitors.
PMID- 27491939
TI - Piptadenin, a Novel 3,4-Secooleanane Triterpene and Piptadenamide, a New Ceramide
from the Stem Bark of Piptadeniastrum africanum (Hook.f.) Brenan.
AB - Piptadenin (1), a new triterpene along with piptadenamide (10), a new ceramide,
have been isolated from the AcOEt-soluble fraction of the MeOH extract of the
stem bark of Piptadeniastrum africanum along with nine known compounds, 1-O
[(3beta,22beta)-3,22-dihydroxy-28-oxoolean-12-en-28-yl]-beta-d-glucopyranose (2),
22beta-hydroxyoleanic acid (3), oleanic acid (4), lupeol (5), betulinic acid (6),
5alpha-stigmasta-7,22-dien-3beta-ol (7), 5alpha-stigmasta-7,22-dien-3-one (8),
(3beta)-stigmast-5-en-3-yl beta-d-glucopyranoside (9) and 2,3-dihydroxypropyl
hexacosanoate (11). Except for compound 11, all the isolated compounds are
reported for the first time from this plant. The structures of the isolated
compounds were elucidated by spectroscopic data including 1D and 2D NMR. The pure
compounds 1 - 11 were subjected to the pharmacological screening and compounds 2,
5 - 7 and 9 exhibited potent urease inhibitory activity with IC50 value of 25.8,
28.9, 30.1, 31.8 and 32.7 MUm, respectively, whereas compound 1 showed moderate
activity (IC50 = 98.7 MUm). The potent urease inhibitory activity supplemented
the previous literature reports and medicinal uses of this plant.
PMID- 27491940
TI - Identification and transcript profiles of citrus growth-regulating factor genes
involved in the regulation of leaf and fruit development.
AB - Growth-regulating factor (GRF) is an important protein in GA-mediated response,
with key roles in plant growth and development. However, it is not known whether
or how the GRF proteins in citrus to regulate organ size. In this study, nine
citrus GRF genes (CsGRF1-9) were validated from the 'Anliu' sweet orange (AL,
Citrus sinensis cv. Anliu) by PCR amplification. They all contain two conserved
motifs (QLQ and WRC) and have 3-4 exons. The transcript levels of genes were
detected by qRT-PCR. Transcript analysis showed that (1) CsGRF 1, 2, 5, 6, 7, and
9 expressed predominantly in young leaf, CsGRF 3 and 4 expressed predominantly in
fruit immature juice sacs and CsGRF 8 expressed predominantly in root; (2) all
citrus GRF genes had significantly higher expression in young leaves than mature
leaf; (3) in juice sacs, the transcript levels of CsGRF1, 4, 5, 6, and 8
increased significantly while the transcript levels of CsGRF2, 3, 7, and 9 had no
significant change from 80 DAF to 100 DAF. Besides, GA3 treatment did not affect
the transcript levels of CsGRF5 and CsGRF6 but significantly increased the
transcript levels of the other seven CsGRF genes in young leaves. These results
suggested that all CsGRF genes involve in the leaf development, CsGRF1, 4, 5, 6,
and 8 act developmentally whilst CsGRF2, 3, 7, and 9 play fundamental roles in
fruit cell enlargement, which may be through GA pathway or GA-independent
pathway.
PMID- 27491941
TI - Obstetrical outcomes of emergency compared with elective cervical cerclage.
AB - OBJECTIVE: To study obstetric outcomes of emergency cerclage compared with
elective cerclage. STUDY DESIGN: Retrospective cohort study of pregnancy outcomes
of patients who underwent cervical cerclage, performed according to ACOG
guidelines, between January 2006 and December 2014. Patients who underwent
emergency cerclage, due to cervical shortening or cervical dilation (emergency
cerclage group) were compared with patients who underwent history-indicated
cerclage (elective cerclage group). Emergency cerclage was not performed in
patients with uterine contractions, vaginal bleeding, or signs of
chorioamnionitis. Procedure-related complications were defined as rupture of
membranes or chorioamnionitis occurring after cerclage placement and before 24
weeks of gestation. RESULTS: Overall, 154 patients with elective cerclage and 47
patients with emergency cerclage were included. Mean gestational age at cerclage
operation was 13.1 +/- 1 and 20.2 +/- 3 weeks, respectively. There were no
differences between the emergency cerclage group and the elective cerclage group
regarding mean gestational age at delivery (36.1 +/- 3 versus 35.6 +/- 3,
respectively, p = 0.7), rate of deliveries beyond 34 weeks of gestation (81.81%
versus 78.72%, respectively, p = 0.67), rate of deliveries beyond 37 weeks of
gestation (64.93% versus 59.57%, respectively, p = 0.6), cesarean deliveries
(33.11% versus 39.13%, p = 0.48, respectively), or birthweight (2848 versus 2862
grams, respectively, p = 0.9). Regarding procedure-related complications, there
were no differences between the elective and the emergency cerclage groups in the
rate of chorioamnionitis (1.29% versus 4.34%, respectively, p = 0.22), or
ruptured membranes (1.29% versus 4.34%, respectively, p = 0.22). CONCLUSION:
Pregnancy outcomes of emergency cerclage are comparable with those of elective
cerclage.
PMID- 27491942
TI - Narrative as re-fusion: Making sense and value from sickle cell and thalassaemia
trait.
AB - The moral turn within sociology suggests that we need to be attentive to values
and have a rapprochement with philosophy. The study of illness narratives is one
area of sociology that has consistently addressed itself to moral domains but has
tended to focus on stories of living with genetic or chronic illness per se
rather than liminal states such as genetic traits. This article takes the case of
genetic carriers within racialized minority groups, namely, those with sickle
cell or thalassaemia trait, and takes seriously the notion that their narratives
are ethical practices. In line with the work of Paul Ricoeur, such storied
practices are found to link embodiment, social relationships with significant
others and wider socio-cultural and socio-political relations. At the same time,
such practices are about embodying values. These narratives may be considered as
practices that re-fuse what genetic counselling has de-fused, in order to make
sense of a life in its entirety and to strive ethically and collectively towards
preferred social realities.
PMID- 27491943
TI - Practices of partnership: Negotiated safety among couples who inject drugs.
AB - Despite the majority of needle-syringe sharing occurring between sexual partners,
the intimate partnerships of people who inject drugs have been largely overlooked
as key sites of both hepatitis C virus prevention and transmission, and risk
management more generally. Drawing on interviews with 34 couples living in inner
city Australia, this article focuses on participants' accounts of 'sharing'.
While health promotion discourses and conventional epidemiology have tended to
interpret the practice of sharing (like the absence of condom use) in terms of
'noncompliance', we are interested in participants' socially and relationally
situated 'rationalities'. Focussing on participants' lived experiences of
partnership, we endeavour to make sense of risk and safety as the participants
themselves do.How did these couples engage with biomedical knowledge around
hepatitis C virus and incorporate it into their everyday lives and practices?
Revisiting and refashioning the concept of 'negotiated safety' from its origins
in gay men's HIV prevention practice, we explore participants' risk and safety
practices in relation to multiple and alternative framings, including those which
resist or challenge mainstream epidemiological or health promotion positions.
Participant accounts revealed the extent to which negotiating safety was a
complex and at times contradictory process, involving the balancing or
prioritising of multifarious, often competing, risks. We argue that our
positioning of participants' partnerships as the primary unit of analysis
represents a novel and instructive way of thinking about not only hepatitis C
virus transmission and prevention, but the complexities and contradictions of
risk production and its negotiation more broadly.
PMID- 27491944
TI - All care, but whose responsibility? Community juries reason about expert and
patient responsibilities in prostate-specific antigen screening for prostate
cancer.
AB - General practitioners have implicitly been given responsibility for guiding men's
decisions about prostate-specific antigen-based screening for prostate cancer,
but patients' expectations of the bounds of this responsibility remain unclear.
We sought to explore how well-informed members of the public allocate
responsibilities in prostate-specific antigen screening decision-making. In 2014,
we convened two Community juries in Sydney, Australia, to address questions
related to the content and timing of information provision and respective roles
of patients and general practitioners in screening decisions. Participants in the
first jury were of mixed gender and of all ages (n = 15); the participants in the
second jury were all male and of screening age (n = 12). Both juries were
presented with balanced factual evidence on the harms and benefits of prostate
specific antigen screening and expert perspectives on ethico-legal aspects of
consent in medical practice. In their deliberations, jurors agreed that general
practitioners should take responsibility for informing men of the options, risks
and benefits of prostate-specific antigen testing, but arrived at different
positions on whether or not general practitioners should also guide screening
decisions. Jurors also disagreed on how much and when general practitioners
should provide detailed information about biopsies and treatments. These
responses suggest that for prostate-specific antigen testing, there is a public
expectation that both the allocation of responsibility between general
practitioners and their male patients, and the level of information provided will
be tailored to individual men. In the presence of expert uncertainty, a well
informed public may have reason to embrace or resist shared decision-making
processes.
PMID- 27491945
TI - Shape morphing Kirigami mechanical metamaterials.
AB - Mechanical metamaterials exhibit unusual properties through the shape and
movement of their engineered subunits. This work presents a new investigation of
the Poisson's ratios of a family of cellular metamaterials based on Kirigami
design principles. Kirigami is the art of cutting and folding paper to obtain 3D
shapes. This technique allows us to create cellular structures with engineered
cuts and folds that produce large shape and volume changes, and with extremely
directional, tuneable mechanical properties. We demonstrate how to produce these
structures from flat sheets of composite materials. By a combination of
analytical models and numerical simulations we show how these Kirigami cellular
metamaterials can change their deformation characteristics. We also demonstrate
the potential of using these classes of mechanical metamaterials for shape change
applications like morphing structures.
PMID- 27491946
TI - Guidance from an in situ hot stage in TEM to synthesize magnetic metal
nanoparticles from a MOF.
AB - A series of in situ hot stage experiments using transmission electron microscopy
(TEM) were studied to directly observe the transition of a Ni-MOF to Ni
nanoparticles wrapped in carbon (Ni-NPC) over temperatures ranging from ambient
temperature to 700 degrees C. Ni-NPC-600 displays high catalytic activity in 4
nitrophenol reduction and high conversion, even after 10 cycles.
PMID- 27491947
TI - The cooperativity effect in the reaction of soluble quinoprotein (PQQ-containing)
glucose dehydrogenase is not due to subunit interaction but to substrate-assisted
catalysis.
AB - : Soluble quinoprotein (PQQ-containing) glucose dehydrogenase (sGDH, EC
1.1.99.35) catalyzes the oxidation of beta-d-glucose to d-glucono-delta-lactone.
Although sGDH has many analytical applications, the relationship between activity
and substrate concentration is not well established. Previous steady-state
kinetic studies revealed a negative cooperativity effect which has recently been
ascribed to subunit interaction. To investigate this conclusion, stopped-flow
kinetic experiments were carried out on the reaction in which oxidized enzyme
(Eox ) was reduced with substrates to Ered . The appearance of Ered is observed
to be preceded by formation of an intermediate enzyme form, Int, which is mono
exponentially formed from Eox . However, the rate of conversion of Int into Ered
depends hyperbolically on the concentration of substrate (leading to a 35-fold
stimulation in the case of glucose). Evidence is provided that substrate not only
binds to Eox but also to Int and Ered as well, and that the binding to Int causes
the significant stimulation of Int decay. It is proposed that a proton shuffling
step is involved in the decay, which is facilitated by binding of substrate to
Int. Substituting the PQQ-activating Ca by a Ba ion lowered all reaction rates
but did not change the stimulation factor. In summary, the previous proposal that
the cooperativity effect of sGDH is due to interaction between its substrate
loaded subunits is incorrect; it is due to substrate-assisted catalysis of the
enzyme. ENZYMES: EC 1.1.99.35 - soluble quinoprotein glucose dehydrogenase.
PMID- 27491948
TI - Prenatal metal exposure in the Middle East: imprint of war in deciduous teeth of
children.
AB - In war zones, the explosion of bombs, bullets, and other ammunition releases
multiple neurotoxicants into the environment. The Middle East is currently the
site of heavy environmental disruption by massive bombardments. A very large
number of US military bases, which release highly toxic environmental
contaminants, have also been erected since 2003. Current knowledge supports the
hypothesis that war-created pollution is a major cause of rising birth defects
and cancers in Iraq. We created elemental bio-imaging of trace elements in
deciduous teeth of children with birth defects from Iraq. Healthy and naturally
shed teeth from Lebanon and Iran were also analyzed for trace elements. Lead (Pb)
was highest in teeth from children with birth defects who donated their teeth
from Basra, Iraq (mean 0.73-16.74 (208)Pb/(43)Ca ppm, n = 3). Pb in healthy
Lebanese and Iranian teeth were 0.038-0.382 (208)Pb/(43)Ca ppm (n = 4) and 0.041
0.31 (208)Pb/(43)Ca ppm (n = 2), respectively. Our hypothesis that increased war
activity coincides with increased metal levels in deciduous teeth is confirmed by
this research. Lead levels were similar in Lebanese and Iranian deciduous teeth.
Deciduous teeth from Iraqi children with birth defects had remarkably higher
levels of Pb. Two Iraqi teeth had four times more Pb, and one tooth had as much
as 50 times more Pb than samples from Lebanon and Iran.
PMID- 27491949
TI - Quantitative assessment of possible human health risk associated with consumption
of arsenic contaminated groundwater and wheat grains from Ropar Wetand and its
environs.
AB - Arsenic (As) is a carcinogenic metalloid that enters food chain through food and
water and poses health risk to living beings. It is important to assess the As
status in the environment and risks associated with it. Hence, a risk assessment
study was conducted across Ropar wetland, Punjab, India and its environs in pre
monsoon season of 2013, to estimate the risk posed to adults and children via
daily consumption of As contaminated groundwater and wheat grains. Arsenic
concentrations determined in groundwater, soil and wheat grain samples using
atomic absorption spectrometer ranged from 2.90 to 10.56 MUg L(-1), 0.06 to 0.12
mg kg(-1) and 0.03 to 0.21 mg kg(-1), respectively. Arsenic in wheat grains
showed significant negative correlation with phosphate content in soil indicating
a competitive uptake of arsenate and phosphate ions by plants. Principal
component analysis and cluster analysis suggested that both natural and
anthropogenic factors contribute to variation in As content and other variables
studied in soil and groundwater samples. Total cancer risk and hazard index were
higher than the USEPA safety limits of 1.00 * 10(-6) and 1, respectively, for
both adults and children indicating a high risk of cancer and other health
disorders. Consumption of As contaminated wheat grains was found to pose higher
risk of cancer and non-cancer health disorders as compared to intake of As
contaminated groundwater by both adults and children. Moreover, children were
found to be more prone to cancer and other heath disorders due to As exposure via
wheat grains and groundwater as compared to adults.
PMID- 27491950
TI - The Impact of Nursing Home Pay-for-Performance on Quality and Medicare Spending:
Results from the Nursing Home Value-Based Purchasing Demonstration.
AB - OBJECTIVE: To evaluate the impact of the Nursing Home Value-Based Purchasing
demonstration on quality of care and Medicare spending. DATA SOURCES/STUDY
SETTING: Administrative and qualitative data from Arizona, New York, and
Wisconsin nursing homes over the base-year (2008-2009) and 3-year (2009-2012)
demonstration period. STUDY DESIGN: Nursing homes were randomized to the
intervention in New York, while the comparison facilities were constructed via
propensity score matching in Arizona and Wisconsin. We used a difference-in
difference analysis to compare outcomes across the base-year relative to outcomes
in each of the three demonstration years. To provide context and assist with
interpretation of results, we also interviewed staff members at participating
facilities. PRINCIPAL FINDINGS: Medicare savings were observed in Arizona in the
first year only and Wisconsin for the first 2 years; no savings were observed in
New York. The demonstration did not systematically impact any of the quality
measures. Discussions with nursing home administrators suggested that facilities
made few, if any, changes in response to the demonstration, leading us to
conclude that the observed savings likely reflected regression to the mean rather
than true savings. CONCLUSION: The Federal nursing home pay-for-performance
demonstration had little impact on quality or Medicare spending.
PMID- 27491951
TI - VCO2 calorimetry is a convenient method for improved assessment of energy
expenditure in the intensive care unit.
PMID- 27491952
TI - Transition from two-dimensional photonic crystals to dielectric metasurfaces in
the optical diffraction with a fine structure.
AB - We study experimentally a fine structure of the optical Laue diffraction from two
dimensional periodic photonic lattices. The periodic photonic lattices with the
C4v square symmetry, orthogonal C2v symmetry, and hexagonal C6v symmetry are
composed of submicron dielectric elements fabricated by the direct laser writing
technique. We observe surprisingly strong optical diffraction from a finite
number of elements that provides an excellent tool to determine not only the
symmetry but also exact number of particles in the finite-length structure and
the sample shape. Using different samples with orthogonal C2v symmetry and
varying the lattice spacing, we observe experimentally a transition between the
regime of multi-order diffraction, being typical for photonic crystals to the
regime where only the zero-order diffraction can be observed, being is a clear
fingerprint of dielectric metasurfaces characterized by effective parameters.
PMID- 27491953
TI - Pigment retinopathy in warmblood horses with equine degenerative
myeloencephalopathy and equine motor neuron disease.
AB - OBJECTIVE: A pigment retinopathy has been reported in adult horses with equine
motor neuron disease (EMND) arising from chronic alpha-tocopherol (alpha-TP)
deficiency. A pigment retinopathy has not been identified in horses with
neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) that
affects genetically susceptible young horses with alpha-TP deficiency. The
objective of this report is to describe, for the first time, a pigment
retinopathy in a family of alpha-TP-deficient Warmbloods (WB) with clinically
apparent NAD/EDM or EMND. ANIMALS AND PROCEDURES: Twenty-five WB horses from one
farm underwent complete neurologic and ophthalmic examinations and serum alpha-TP
concentrations were assessed. Two of the most severely ataxic horses were
euthanized and postmortem examinations performed. RESULTS: Alpha-TP deficiency
was widespread on this farm (22 of 25 horses). Eleven of 25 horses were
clinically normal (age range 2-12 years), one had signs of EMND (6 years of age),
10 had signs of ataxia consistent with NAD/EDM (1-10 years), and two of these
were postmortem confirmed concurrent NAD/EDM and EMND. A pigment retinopathy
characterized by varying amounts of granular dark pigment in the tapetal retina
was observed in four clinically apparent NAD/EDM horses (two postmortem confirmed
concurrent NAD/EDM and EMND) and one horse with clinical signs of EMND.
CONCLUSIONS: A pigment retinopathy can be present in young alpha-TP-deficient
Warmblood horses with clinical signs of EMND as well as those with signs of
NAD/EDM.
PMID- 27491956
TI - A Single Center Prospective Observational Study of Outcomes With Tonic Cervical
Spinal Cord Stimulation.
AB - BACKGROUND: Spinal cord stimulation (SCS) has been a valuable resource for the
treatment of chronic, nonmalignant pain that persists in the face of maximal
medical management. A recent study demonstrated efficacy of cervical SCS in a
multicenter registry. Here, in our single center study, we are able to delve into
patient specifics, explore outcomes with percutaneous vs. paddle implants, and
examine impact of patient symptomatology. METHODS: We prospectively collected
data on subjects who underwent cervical SCS via numeric rating scale (NRS),
McGill Pain Questionnaire, Oswestry Disability Index (ODI), and Beck Depression
Inventory. Subjects completed this battery pre-operatively, at six months and at
one year. Data were analyzed via repeated measures ANOVA, bivariate correlation
analysis, and paired t-tests. RESULTS: In 30 consecutive subjects, 24 had a
complete data set. The diagnosis was failed neck surgery syndrome (13%), Complex
regional pain syndrome (29%), and neuropathic pain (58%). Compared with baseline,
NRS score significantly improved at six months (p = 0.021) and one year (p =
0.047). ODI score also improved at one year (p = 0.009). At both six months and
one year, subjects with percutaneous implants reported significantly less
disability on ODI (p = 0.016 and 0.034, respectively), as compared with those who
received paddle implants. There was no difference in NRS score or any other
outcome measure based on type of implant. Diagnosis or region of pain did not
correlate with any measure of outcome. DISCUSSION: We demonstrate that neck and
arm pain can be improved with cervical SCS at six month and one-year follow-ups.
Both percutaneous and paddle implants have benefit. We tend to place percutaneous
implants for radicular pain and retrograde C1-2 paddles for axial pain that is
ineffectively treated during the trial.
PMID- 27491957
TI - Understanding Systematic Reviews and Meta-Analyses [Formula: see text].
AB - Systematic reviews should be distinguished from narrative reviews. In the latter,
an editor asks an expert to sum up all of the information that is known about a
particular topic. However, the expert is under no constraints regarding what he
or she does, or does not, choose to include in the review. As a result, his or
her bias can influence the final message. A systematic review, which may or may
not be written by experts, typically asks a narrower question, and then answers
it using the entirety of the medical literature. The systematic review process
includes computer searches to identify the pertinent literature, a statement of
the inclusion and exclusion criteria for identified studies, a list of items of
interest to extract from each study, a method to assess the quality of each
study, a summary of the evidence that has been found (which may or may not
involve attempts to combine data), a discussion of the evidence and the
limitations of the conclusions, and suggestions for future research efforts. If
the data are combined, that process is called meta-analysis. In meta-analysis, an
estimate of the reliability of each study is made, and those that appear to be
more reliable are weighed more heavily when the data are combined. While
systematic reviews depend on a more preplanned method and thus, unlike narrative
reviews, contain sections on method, they can be easily read once the reader
becomes familiar with the vocabulary.
PMID- 27491955
TI - Control of the heat stress-induced alternative splicing of a subset of genes by
hnRNP K.
AB - Pre-mRNA splicing is widely repressed upon heat shock in eukaryotic cells.
However, it has been shown that HSP105 pre-mRNA is alternatively spliced in
response to heat stress. Using RNAi screening in HeLa cells, we found that RNA
binding proteins hnRNP K and PSF/SFPQ are necessary for the exon 12 exclusion of
HSP105 during heat stress. Moreover, exon array analyses showed that a group of
genes is alternatively spliced during heat stress in an hnRNP K-dependent manner,
whereas hnRNP K is not necessary for the stress-induced alternative splicing of
the remaining genes. Among the latter group, we found that SRp38/SRSF10 and
SC35/SRSF2 are necessary for the inclusion of exon 13 of TNRC6A during heat
stress. Thus, our study clearly showed that several RNA-binding proteins are
involved in the splicing regulation in response to heat stress in mammalian
cells.
PMID- 27491954
TI - The Expression of Human Cytomegalovirus MicroRNA MiR-UL148D during Latent
Infection in Primary Myeloid Cells Inhibits Activin A-triggered Secretion of IL
6.
AB - The successful establishment and maintenance of human cytomegalovirus (HCMV)
latency is dependent on the expression of a subset of viral genes. Whilst the
exact spectrum and functions of these genes are far from clear, inroads have been
made for protein-coding genes. In contrast, little is known about the expression
of non-coding RNAs. Here we show that HCMV encoded miRNAs are expressed de novo
during latent infection of primary myeloid cells. Furthermore, we demonstrate
that miR-UL148D, one of the most highly expressed viral miRNAs during latent
infection, directly targets the cellular receptor ACVR1B of the activin
signalling axis. Consistent with this, we observed upregulation of ACVR1B
expression during latent infection with a miR-UL148D deletion virus (DeltamiR
UL148D). Importantly, we observed that monocytes latently infected with DeltamiR
UL148D are more responsive to activin A stimulation, as demonstrated by their
increased secretion of IL-6. Collectively, our data indicates miR-UL148D inhibits
ACVR1B expression in latently infected cells to limit proinflammatory cytokine
secretion, perhaps as an immune evasion strategy or to postpone cytokine-induced
reactivation until conditions are more favourable. This is the first
demonstration of an HCMV miRNA function during latency in primary myeloid cells,
implicating that small RNA species may contribute significantly to latent
infection.
PMID- 27491958
TI - Parental presence at induction of anesthesia is feasible with minimal preparation
and resources.
PMID- 27491959
TI - Small molecule-assisted fabrication of black phosphorus quantum dots with a
broadband nonlinear optical response.
AB - Ultrathin BP QDs with a uniform size of ~3.4 nm were prepared via small molecule
assisted liquid phase exfoliation and they exhibited superior broadband nonlinear
saturable absorption promising for nonlinear optical applications. Laser
photolysis measurement implied that the nonlinear response origin was related to
the long-lived electron-hole pairs delocalized within the BP QDs.
PMID- 27491960
TI - A Review of Hormonal Contraception and Venous Thromboembolism in Adolescents.
AB - BACKGROUND: The number of adolescents who are prescribed hormonal contraception
(HC) for contraceptive and noncontraceptive indications is increasing.
Approximately 1 of 4 female adolescents will use some form of HC by age 19 years.
Venous thromboembolism (VTE) is a rare, but life-threatening complication
associated with HC use. Although adolescents aged 15 to 19 years have the lowest
absolute HC-associated VTE risk, they still account for 5.9% of HC-associated
VTE. The absolute HC-associated VTE risk for those younger than 15 years of age
is not well described. OBJECTIVE: The objectives of this report are to describe
the current literature regarding HC-associated VTE in adolescents, to review the
coagulation cascade and in vivo coagulation, to highlight differences between the
adolescent and adult coagulation profiles, to discuss coagulation profile changes
related to HC use, and to identify knowledge deficits for future study.
CONCLUSION: The mechanisms and confounding variables that lead to HC-associated
VTE in all adolescents are not well understood because many large HC studies
exclude female adolescents younger than 18 years of age. Because of the paucity
of data in this age group, observational studies and randomized controlled trials
of VTE risk in adolescents on varying forms of HC are needed. Studies should
include female adolescents across the entire adolescent age span (12-21 years) to
better understand HC-associated VTE risk in this population.
PMID- 27491961
TI - Alcohol use among adults in Uganda: findings from the countrywide non
communicable diseases risk factor cross-sectional survey.
AB - BACKGROUND: There are limited data on levels of alcohol use in most sub-Saharan
African countries. OBJECTIVE: We analyzed data from Uganda's non-communicable
diseases risk factor survey conducted in 2014, to identify alcohol use prevalence
and associated factors. DESIGN: The survey used the World Health Organization
STEPS tool to collect data, including the history of alcohol use. Alcohol users
were categorized into low-, medium-, and high-end users. Participants were also
classified as having an alcohol-use-related disorder if, over the past 12 months,
they were unable to stop drinking alcohol once they had started drinking, and/or
failed to do what was normally expected of them because of drinking alcohol,
and/or needed an alcoholic drink first in the morning to get going after a heavy
drinking session the night before. Weighted logistic regression analysis was used
to identify factors associated with medium- to high-end alcohol use. RESULTS: Of
the 3,956 participants, 1,062 (26.8%) were current alcohol users, including 314
(7.9%) low-end, 246 (6.2%) medium-end, and 502 (12.7%) high-end users. A total of
386 (9.8%) were classified as having an alcohol-use-related disorder. Male
participants were more likely to be medium- to high-end alcohol users compared to
females; adjusted odds ratio (AOR)=2.34 [95% confidence interval (CI)=1.88-2.91].
Compared to residents in eastern Uganda, participants in central and western
Uganda were more likely to be medium- to high-end users; AOR=1.47 (95% CI=1.01
2.12) and AOR=1.89 (95% CI=1.31-2.72), respectively. Participants aged 30-49
years and those aged 50-69 years were more likely to be medium- to high-end
alcohol users, compared to those aged 18-29 years, AOR=1.49 (95% CI=1.16-1.91)
and AOR=2.08 (95% CI=1.52-2.84), respectively. CONCLUSIONS: The level of alcohol
use among adults in Uganda is high, and 9.8% of the adult population has an
alcohol-use-related disorder.
PMID- 27491962
TI - Barriers to successful treatment of alcohol addiction as perceived by healthcare
professionals in Thailand - a Delphi study about obstacles and improvement
suggestions.
AB - BACKGROUND: Many Thai people experiencing alcohol addiction do not seek help, and
those who do often have inadequate access to treatment. There are few research
studies focusing on alcohol addiction treatment in Thailand. OBJECTIVE: The
purpose of the current study was to identify barriers to the treatment of alcohol
addiction and to collect experts' suggestions for improving treatment in
Thailand. The Delphi technique was used to achieve consensual agreement among an
expert panel within the field of alcohol addiction and treatment. DESIGN: Three
rounds of a Delphi survey were completed by a panel of experts in alcohol
addiction, including physicians, nurses, social workers, psychologists,
healthcare officers, and an Alcoholics Anonymous member. The open-ended answers
provided by 34 experts in the first round resulted in 60 statements, which were
later grouped into three themes. After three rounds of questionnaires, 51
statements were accepted as consensus. RESULTS: Thirty-two experts participated
in all three Delphi rounds. Over 80% of participants were particularly concerned
about five obstacles to alcohol addiction treatment. The majority of suggestions
from the expert panel were related to patients' right to treatment and the
national policy for reducing the negative effects of alcohol. According to the
results of the present study, the experts suggested that the treatment of alcohol
addiction should be continuous from primary care to tertiary care, and convenient
pathways should be established in healthcare services. The experts would also
like to increase the number of healthcare providers and improve their knowledge
and skills in working with people experiencing alcohol addiction. CONCLUSIONS:
Equal rights to health and treatment for people experiencing alcohol addiction in
Thailand require policy improvements, as well as acceptance and awareness of
alcohol addiction from both the public and policymakers.
PMID- 27491963
TI - HOSPITAL-BASED HEALTH TECHNOLOGY ASSESSMENT (HB-HTA): A 10-YEAR SURVEY AT ONE
UNIT.
AB - INTRODUCTION: Hospital-based health technology assessment (HB-HTA) has been
introduced to help hospital management in decision making about the adoption of
new health technologies (HTs). We reviewed the accuracy of the expected medical
impact of HTs assessed at our hospital, as well as the acceptance of this process
by clinicians. METHODS: For each HT adopted between 2002 and 2011, a semi
structured interview with the involved clinician was conducted, assessing (i) the
perceived utility of the HB-HTA process, (ii) the accuracy of the new HT's
expected medical impact as compared with observed patient data from the year
2012, and (iii) the compliance with the indications of the HB-HTA report.
RESULTS: Over the 10-year period, forty HB-HTAs were carried out, of which thirty
four led to acceptance. Twenty-seven of the twenty-eight clinicians involved in
these thirty-four HTs accepted the interview and 85 percent acknowledged the
utility of the HB-HTA process. Five of the thirty-four HTs were no longer in use.
For the twenty-nine remaining HTs, observed patients' number was as expected in
eight, higher in four, lower in fifteen, and not available in two cases.
Available average length of stay was 61 percent longer than expected. Two HTs had
a higher complication rate and three a lower success rate. Indications evolved in
55 percent of HTs after a few years (seven restrictions, six broadenings, and
three other changes). CONCLUSIONS: A HB-HTA process is useful to improve quality
in decision making. Follow-up analysis should routinely be performed to adapt HB
HTA reports' conclusions to practical experience and new scientific evidence.
PMID- 27491964
TI - Development and Validation of a Quality Assurance Score for Robot-assisted
Radical Cystectomy: A 10-year Analysis.
AB - OBJECTIVE: To develop quality assessment tool to evaluate surgical performance
for robot-assisted radical cystectomy program. METHODS: A prospectively
maintained quality assurance database of 425 consecutive robot-assisted radical
cystectomies performed by a single surgeon between 2005 and 2015 was
retrospectively reviewed. Potentially modifiable factors, related to the
management and perioperative care of patients, were used to evaluate patient
care. Criteria included the following: preoperative (administration of
neoadjuvant chemotherapy); operative (operative time <6.5 hours and estimated
blood loss <500 cc); pathologic (negative soft tissue surgical margins and lymph
node yield >=20); and postoperative (no high-grade complications, readmission, or
noncancer-related mortality within 30 days).The Quality Cystectomy Score (QCS)
was developed (1 star: achieving <=2 criteria or mortality within 30 days; 2
stars: 3 or 4 criteria met; 3 stars: 5 or 6 criteria met; and 4 stars: 7 or all
criteria met). Univariate and multivariate Cox proportional hazard regression
models were fitted to test for the association between QCS and survival outcomes.
RESULTS: Most patients (85%) achieved at least 3 stars, and more patients
achieved 4 stars with time. High QCS was associated with better recurrence-free,
cancer-specific, and overall survival (P values <.05). None of the patients with
1-star were alive at 1 year. Patients with 4 stars achieved the best survival
rates (recurrence-free survival [62%], cancer-specific survival [70%], and
overall survival [53%] at 5 years) (log rank P < .0001). CONCLUSION: Continuous
assessment for quality improvement facilitated implementation and maintenance of
robot-assisted program for bladder cancer.
PMID- 27491965
TI - Projecting the Urology Workforce Over the Next 20 Years.
AB - OBJECTIVE: To forecast the size and composition of the urologist and urology
advanced care provider (ACP; nurse practitioner, physicians' assistant) workforce
over the next 20 years. METHODS: Current urologist workforce was estimated from
the American Board of Urology certification data and the 2014 American Urological
Association (AUA) Census. Incoming workforce was estimated from the American
Board of Urology and AUA residency match data. Estimates of the ACP workforce
were extracted from the 2012 AUA Physician Survey. Full-time equivalent (FTE)
calculations were based on a 2014 urology workforce survey. Workforce projections
were created using a stock and flow population model with multiple alternative
forecast scenarios. RESULTS: Slight growth in overall (urologist + ACP) workforce
FTEs is expected, from 14,792 in 2015 to 15,160 in 2035. A significant decline in
urologist FTEs is likely, from 11,221 in 2015 to 8859 in 2035. ACPs should
increase markedly, from 8,710 in 2015 to 15,369 in 2035. Female urologists should
increase by 2035, from the current 7.0% to 18.6% of urologist workforce.
Alternate scenarios were evaluated, with forecasted FTEs in 2035 ranging from
14,066 to 17,675. In 2035, workforce shortage predictions range from 12% to 46%.
CONCLUSION: With a decrease in urologists over the coming decades, urologists and
ACPs may not meet future demand. This forecast highlights the need for discussion
and planning among leadership in the field to find creative solutions for this
impending workforce shortage.
PMID- 27491966
TI - Explanatory model of psychosis: impact on perception of self-stigma by patients
in three sub-saharan African cities.
AB - BACKGROUND: Most cultures in sub-Saharan Africa subscribe to the belief that the
root cause of psychosis is supernatural. Individuals in the community who hold a
religiomagical explanatory model of causation have been shown to exhibit more
stigmatizing attitudes towards people with psychosis. Self-stigma among
individuals with psychosis is less frequently studied. METHOD: We used a mixed
method approach, consisting of key informant's interviews to elicit information
on explanatory models of causation of psychosis and questionnaire assessment of
internalized stigma with an adapted version of the Scale for Internalized Stigma
of Mental Illness. Twenty-four, 31, and 30 subjects with recent experience of
utilizing the service of traditional or faith healers for severe mental disorders
in Ibadan (Nigeria), Kumasi (Ghana), and Nairobi (Kenya), respectively, were
interviewed. RESULTS: About 44 % (42.1 %) of the Nigerian respondents had a high
(severe) level of self-stigma with the respective proportions among Ghanaian and
Kenyan respondents being 20.7 and 37.5 %. Compared with 4 out of a total of 12
respondents (33.3 %) who reported low self-stigma reported supernatural
attribution, 14 out of 20 respondents (70 %) with the highest level of self
stigma reported supernatural attribution across the three sites. When low scorers
ascribed supernatural causation, it was often with a religious focus. CONCLUSION:
There is a greater tendency for persons with high levels of self-stigma than
those with low levels to ascribe supernatural attribution to their experience of
a severe mental health condition.
PMID- 27491967
TI - Social influences on eating and physical activity behaviours of urban, minority
youths.
AB - OBJECTIVE: Social relationships can impact youths' eating and physical activity
behaviours; however, the best strategies for intervening in the social
environment are unknown. The objectives of the present study were to provide in
depth information on the social roles that youths' parents and friends play
related to eating and physical activity behaviours and to explore the impact of
other social relationships on youths' eating and physical activity behaviours.
DESIGN: Convergent parallel mixed-methods design. SETTING: Low-income, African
American, food desert neighbourhoods in Baltimore City, MD, USA. SUBJECTS: Data
were collected from 297 youths (53 % female, 91 % African American, mean age 12.3
(sd 1.5) years) using structured questionnaires and combined with in-depth
interviews from thirty-eight youths (42 % female, 97 % African American, mean age
11.4 (sd 1.5) years) and ten parents (80 % female, 50 % single heads of house,
100 % African American). RESULTS: Combined interpretation of the results found
that parents and caregivers have multiple, dynamic roles influencing youths'
eating and physical activity behaviours, such as creating health-promoting rules,
managing the home food environment and serving as a role model for physical
activity. Other social relationships have specific, but limited roles. For
example, friends served as partners for physical activity, aunts provided
exposure to novel food experiences, and teachers and doctors provided information
related to eating and physical activity. CONCLUSIONS: Obesity prevention
programmes should consider minority youths' perceptions of social roles when
designing interventions. Specifically, future research is needed to test the
effectiveness of intervention strategies that enhance or expand the supportive
roles played by social relationships.
PMID- 27491968
TI - Multiple timescale mixed bursting dynamics in a respiratory neuron model.
AB - Experimental results in rodent medullary slices containing the pre-Botzinger
complex (pre-BotC) have identified multiple bursting mechanisms based on
persistent sodium current (I NaP) and intracellular Ca2+. The classic two
timescale approach to the analysis of pre-BotC bursting treats the inactivation
of I NaP, the calcium concentration, as well as the Ca2+-dependent inactivation
of IP 3 as slow variables and considers other evolving quantities as fast
variables. Based on its time course, however, it appears that a novel mixed
bursting (MB) solution, observed both in recordings and in model pre-BotC
neurons, involves at least three timescales. In this work, we consider a single
compartment model of a pre-BotC inspiratory neuron that can exhibit both I NaP
and Ca2+ oscillations and has the ability to produce MB solutions. We use methods
of dynamical systems theory, such as phase plane analysis, fast-slow
decomposition, and bifurcation analysis, to better understand the mechanisms
underlying the MB solution pattern. Rather surprisingly, we discover that a third
timescale is not actually required to generate mixed bursting solutions. Through
our analysis of timescales, we also elucidate how the pre-BotC neuron model can
be tuned to improve the robustness of the MB solution.
PMID- 27491969
TI - Smaller tumor size is associated with poor survival in stage II colon cancer: An
analysis of 7,719 patients in the SEER database.
AB - BACKGROUND: We hypothesized that in patients with colon cancer showing heavy
intestinal wall invasion without lymph node metastasis (stage II), small tumor
size would correlate with more aggressive tumor behaviors and thus poorer cancer
specific survival (CSS). METHODS: We analyzed Caucasian patients with stage II
colon cancer based on data from the US Surveillance, Epidemiology, and End
Results (SEER) database. Survival was analyzed using the Kaplan-Meier method, and
the log-rank test was used to identify differences. Risk factors were analyzed
using the Cox proportional hazard model. RESULTS: A total of 7719 stage II colon
cancer patients from the SEER database were included in the analysis. The cutoff
value (5.0 cm) was determined using the X-tile program. The Kaplan-Meier analysis
showed that tumors <5.0 cm had a poorer CSS compared to tumors >=5.0 cm (p =
0.006). Multivariate analysis indicated that tumor size is an independent
prognostic factor for stage II patients, and compared to tumors <5.0 cm, tumors
>=5.0 cm were more likely to result in a better CSS (HR 0.775, 95% CI 0.691
0.870, p < 0.001). Tumor size was also analyzed as a continuous variable in the
multivariate analysis, and the CSS decreased with decreasing tumor size (HR
0.958, 95% CI 0.936-0.981, p < 0.001). Subgroup analyses suggested that tumor
size is also an independent prognostic factor for stage IIA (p = 0.002) and IIC
(p < 0.001) patients. CONCLUSIONS: Smaller tumor size is associated with poor CSS
in the stage II colon cancer and particularly in the stage IIA and IIC subgroups.
PMID- 27491970
TI - Effects of hydrodynamic disturbances and resuspension characteristics on the
release of tetrabromobisphenol A from sediment.
AB - Tetrabromobisphenol A (TBBPA) exists widely in river and lake sediments; it has
raised growing attention in recent years as emerging contaminant due to its
possible threats to the aquatic environment and human health. Using a specialized
simulator, the relationships between hydrodynamic disturbances and resuspension
characteristics were simulated, with an emphasis on microscopic characteristics.
Furthermore, TBBPA release from sediment was studied in relation to hydrodynamic
disturbances and resuspension characteristics. The results show that stronger
water disturbances caused an increase in suspended solids concentration (SSC) and
produced different behaviors of particle size distribution (PSD) and media
diameter (D50) in the slight and large-scale resuspension situations. As for
microscopic resuspension characteristics, the specific surface area (SSA) of
suspended particulate matter (SPM) was very different from that of smooth
particles. This difference may result from the fractal nature of the SPM. The
fractal dimension (FD) of SPM was found to have a significant correlation with
turbulent kinetic energy. TBBPA release into overlying water and adsorption onto
SPM both increased with hydrodynamic disturbances; but the release into overlying
water is more dominant. The TBBPA concentrations in SPM under different
hydrodynamic conditions were significant related to SSA, indicating that SSA is a
key factor affecting the TBBPA adsorption capacity of SPM. TBBPA concentrations
in sediment decreased slightly with the increased hydrodynamic dispersion.
Findings from this research show the importance of considering the hydrodynamic
disturbance and resuspension characteristics in understanding TBBPA release
behavior in aquatic environment.
PMID- 27491971
TI - Size-dependent depletion and community disturbance of phytoplankton under
intensive oyster mariculture based on HPLC pigment analysis in Daya Bay, South
China Sea.
AB - In this study, we conducted a 14-month investigation in Daya Bay, southern China
to understand the effects of oyster farming on phytoplankton community and
biomass by using size-fractionated phytopigments. Results proved the filtering
effects of oysters on phytoplankton biomass. During the oyster culture period,
the average concentration of total chlorophyll a (sum of size-fractionated Chl a)
within the farming area was approximately 60% lower than that at the reference
site. Phytoplankton depletion in the aquaculture zone mainly occurred in micro
sized fractions (>20 MUm) of Chl a, fucoxanthin, and peridinin. The influence of
oyster filtration on nano-sized (2.7-20 MUm) pigments seemed less than that on
micro-sized ones. The depletion of peridinin and 19'-hex-fucoxanthin in
aquaculture zone was higher than those of the other pigments, which indicated
that flagellated cells might be selectively filtered by oysters and could be more
easily influenced by oyster aquaculture. The pico-sized Chl a (<2.7 MUm)
comprised 24% of total Chl a on the average in the aquaculture zone during the
cultural period compared to 6% in the reference site. Picoeukaryote abundance,
which was determined via flow cytometry, was significantly higher in the
aquaculture zone than in the non-aquaculture areas. The abundance of
picoeukaryote is significantly and positively correlated with the concentrations
of pico-sized prasinoxanthin, violaxanthin, and neoxanthin, indicating that
picoeukaryote is dominated by those in prasinophyte. The results suggest that
oyster aquaculture might stimulate the growth of prasinophyte, although the
seasonal variations are mainly controlled by the water temperature in the study
area. This research highlights the successful use of size-fractionated
phytopigments to estimate size-specific phytoplankton biomass and community,
which can be applied as a routine method to monitor the environmental effect and
food resources of bivalve aquaculture.
PMID- 27491972
TI - Prediction of intravenous immunoglobulin resistance in Kawasaki disease in an
East China population.
AB - The objectives of the study were to find the risk factors associated with
intravenous immunoglobulin (IVIG) resistance and generate a prediction scoring
system of IVIG resistance in patients with Kawasaki disease (KD). We
retrospectively reviewed the clinical records of KD patients between January 2006
and December 2014. Multivariate logistic regression was performed to identify the
risk factors of IVIG non-responders. The independent risk factors were used to
construct a new scoring system and compared with Kobayashi and Egami scoring
systems. Multivariate logistic regression analysis identified age <6 months,
rash, edema of extremities, % neutrophils, and serum albumin as independent risk
factors for IVIG non-responders. We assigned one point for rash, edema of
extremities, and % neutrophils >=80 %. Two points were assigned for age <6 months
and serum albumin <35 g/L. Using a cutoff point of three or more, we identified
the IVIG non-responders with 71.4 % sensitivity and 76.0 % specificity. The new
scoring system had a relatively better performance than Kobayashi and Egami
scoring systems in the KD patients in East China. Clinical pediatricians must pay
more attention to these high-risk patients, and use of additional therapies early
in the course of their illness is necessary.
PMID- 27491973
TI - Draft Genome Sequence of Geobacillus subterraneus Strain K, a Hydrocarbon
Oxidizing Thermophilic Bacterium Isolated from a Petroleum Reservoir in
Kazakhstan.
AB - The draft genome sequence of Geobacillus subterraneus strain K, a thermophilic
aerobic oil-oxidizing bacterium isolated from production water of the Uzen high
temperature oil field in Kazakhstan, is presented here. The genome is annotated
for elucidation of the genomic and phenotypic diversity of thermophilic alkane
oxidizing bacteria.
PMID- 27491974
TI - Complete Genome Sequence of Streptococcus agalactiae Strain S25 Isolated from
Peritoneal Liquid of Nile Tilapia.
AB - Streptococcus agalactiae (Lancefield group B; GBS) is one of the major pathogens
in fish production, especially in Nile tilapia (Oreochromis niloticus). The
genomic characteristics of GBS isolated from fish must be more explored. Thus, we
present here the genome of GBS S25, isolated from Nile tilapia from Brazil.
PMID- 27491975
TI - Complete Genome Sequence of a Novel Bacillus sp. VT 712 Strain Isolated from the
Duodenum of a Patient with Intestinal Cancer.
AB - We report here the complete genome sequence of the spore-forming Bacillus sp.
strain VT 712 isolated from the duodenum of a patient with intestinal cancer. The
genome is 3,921,583 bp, with 37.9% G+C content. It contains 3,768 predicted
protein-coding genes for multidrug resistance transporters, virulence factors,
and daunorubicin resistance.
PMID- 27491976
TI - Draft Genome Sequences of Legionella pneumophila JR32 and Lp01 Laboratory Strains
Domesticated in Japan.
AB - We report here the draft genome sequences of two Legionella pneumophila variant
strains (JR32 and Lp01_666) originally derived from a Philadelphia-1 clinical
isolate, domesticated in Japan, with distinct susceptibility to amoebae. Detailed
genomic analysis will allow us to better understand Legionella adaptation and
survival mechanisms in host cells.
PMID- 27491977
TI - Draft Genome Sequence of a Thermophilic Desulfurization Bacterium, Geobacillus
thermoglucosidasius Strain W-2.
AB - Geobacillus thermoglucosidasius strain W-2 is a thermophilic bacterium isolated
from a deep-subsurface oil reservoir in northern China, which is capable of
degrading organosulfur compounds. Here, we report the draft genome sequence of G.
thermoglucosidasius strain W-2, which may help to elucidate the genetic basis of
biodegradation of organosulfur pollutants under heated conditions.
PMID- 27491978
TI - Draft Genome Sequence of Burkholderia stabilis LA20W, a Trehalose Producer That
Uses Levulinic Acid as a Substrate.
AB - Burkholderia stabilis LA20W produces trehalose using levulinic acid (LA) as a
substrate. Here, we report the 7.97-Mb draft genome sequence of B. stabilis
LA20W, which will be useful in investigations of the enzymes involved in LA
metabolism and the mechanism of LA-induced trehalose production.
PMID- 27491979
TI - Draft Genome Sequence of Escherichia coli S51, a Chicken Isolate Harboring a
Chromosomally Encoded mcr-1 Gene.
AB - We present the draft genome of Escherichia coli S51, a colistin-resistant
extended-spectrum beta-lactamase-producing strain isolated in 2015 from raw
chicken meat imported from Germany. Assembly and annotation of this draft genome
resulted in a 4,994,918-bp chromosome and revealed a chromosomally encoded mcr-1
gene responsible for the colistin resistance of the strain.
PMID- 27491980
TI - Permanent Improved High-Quality Draft Genome Sequence of Nocardia casuarinae
Strain BMG51109, an Endophyte of Actinorhizal Root Nodules of Casuarina glauca.
AB - Here, we report the first genome sequence of a Nocardia plant endophyte, N.
casuarinae strain BMG51109, isolated from Casuarina glauca root nodules. The
improved high-quality draft genome sequence contains 8,787,999 bp with a 68.90%
GC content and 7,307 predicted protein-coding genes.
PMID- 27491981
TI - Complete Genome Sequence of the Proteorhodopsin-Containing Marine Flavobacterium
Dokdonia donghaensis DSW-1T, Isolated from Seawater off Dokdo in the East Sea
(Sea of Korea).
AB - Dokdonia spp. have been used for investigating the lifestyles of proteorhodopsin
containing photoheterotrophs and for understanding marine photobiology. Here, we
report the complete genome sequence of Dokdonia donghaensis DSW-1(T) using the
PacBio sequencing platform. It should provide a valuable resource for comparative
genomic studies of marine life harboring microbial rhodopsins among others.
PMID- 27491982
TI - Draft Genome Sequences of Eight Obligate Methane Oxidizers Occupying Distinct
Niches Based on Their Nitrogen Metabolism.
AB - The genome sequences of Methylomonas methanica (NCIMB 11130(T), R-45363, and R
45371), Methylomonas koyamae (R-45378, R-45383, and R-49807), Methylomonas lenta
(R-45370), and Methylosinus sp. (R-45379) were obtained. These aerobic
methanotrophs were isolated from terrestrial ecosystems, and their distinct
phenotypes related to nitrogen assimilation and dissimilation were previously
reported.
PMID- 27491983
TI - First Complete Genome Sequence of Chronic Bee Paralysis Virus Isolated from Honey
Bees (Apis mellifera) in China.
AB - Chronic bee paralysis virus (CBPV) is a serious viral disease affecting adult
bees. We report here the complete genome sequence of CBPV, which was isolated
from a honey bee colony with the symptom of severe crawling. The genome of CBPV
consists of two segments, RNA 1 and RNA 2, containing respective overlapping
fragments.
PMID- 27491984
TI - A Narnavirus-Like Element from the Trypanosomatid Protozoan Parasite Leptomonas
seymouri.
AB - Genome sequences were determined for a novel RNA virus, Leptomonas seymouri Narna
like virus 1 (LepseyNLV1). A 2.9-kb segment encodes an RNA-dependent RNA
polymerase (RdRp), while a smaller 1.5-kb segment showed no database search
matches. This is the first report of bisegmented Narnaviridae from insect
trypanosomatids.
PMID- 27491985
TI - A Novel Bunyavirus-Like Virus of Trypanosomatid Protist Parasites.
AB - We report here the sequences for all three segments of a novel RNA virus
(LepmorLBV1) from the insect trypanosomatid parasite Leptomonas moramango This
virus belongs to a newly discovered group of bunyavirus-like elements termed
Leishbunyaviruses (LBV), the first discovered from protists related to
arboviruses infecting humans.
PMID- 27491986
TI - Draft Genome Sequence of Pseudoalteromonas tetraodonis Strain MQS005, a Bacterium
with Potential Quorum-Sensing Regulation.
AB - We present here the draft genome sequence of Pseudoalteromonas tetraodonis strain
MQS005, a bacterium possessing potential quorum-sensing regulatory activity. This
strain was isolated from water from the South China Sea, People's Republic of
China. The assembly consists of 4,252,538 bp and contains 144 contigs, with a G+C
content of 41.85%.
PMID- 27491987
TI - Draft Genome Sequence of Paenibacillus polymyxa KF-1, an Excellent Producer of
Microbicides.
AB - We report here the draft genome sequence of Paenibacillus polymyxa KF-1, which
exhibits excellent antimicrobial activity. It encodes the synthase of bacitracin,
kalimantacin, bacillomycin, iturin, fusaricidin, tridecaptin, and pelgipeptin and
biosynthetic pathways of antiviral curldan and levan polysaccharides. Also, a
novel prophage is involved in this genome that contains endolysin-encoding genes.
PMID- 27491989
TI - Complete Genome Sequence of Zika Virus Isolated in Mexico, 2016.
AB - Zika virus belongs to the genus Flavivirus, and its spread remains an
international public health emergency. In this report, we describe the obtainment
and molecular characterization of a complete viral genome through the direct
metagenomic analysis from saliva from an autochthonous transmission case in
Mexico.
PMID- 27491988
TI - Draft Genome Sequence of Fonsecaea nubica Strain CBS 269.64, Causative Agent of
Human Chromoblastomycosis.
AB - On the basis of multilocus phylogenetic data, Fonsecaea nubica was described in
2010 as a molecular sibling of F. monophora, an established agent of the human
skin disease chomoblastomycosis in tropical zones. Genome analysis of these
pathogens is mandatory to identify genes involved in the interaction with host
and virulence.
PMID- 27491990
TI - Genome Sequence of Listeria monocytogenes Strain HPB2088 (Serotype 1/2a), an
Environmental Isolate Collected in Canada in 1994.
AB - Listeria monocytogenes is a foodborne pathogen that causes severe illness. Thus,
ongoing efforts at real-time whole-genome sequencing are of utmost importance.
However, it is also important that retrospective analyses that place these data
into context be performed. Here, we present the genome sequence of strain
HPB2088, which was collected in 1994.
PMID- 27491991
TI - Draft Genome Sequence of Capniomyces stellatus, the Obligate Gut Fungal Symbiont
of Stonefly.
AB - Capniomyces stellatus is a host-specific endosymbiotic fungus, living in the
hindgut of stoneflies (especially in Allocapnia). Here, we present the first
draft genome sequence of the fungus, as well as the ab initio gene prediction and
function analyses, which will facilitate the study and comparative analyses of
insect-associated fungi.
PMID- 27491992
TI - Draft Genome Sequences of Two Ureolytic Bacteria Isolated from Concrete Block
Waste.
AB - We sequenced genomes of two ureolytic bacteria, Bacillus sp. JH7 and Sporosarcina
sp. HYO08, which were isolated from concrete waste and have a potential for
biocementation applications.
PMID- 27491993
TI - Draft Genome Sequence of Oil-Degrading Bacterium Gallaecimonas pentaromativorans
Strain YA_1 from the Southwest Indian Ocean.
AB - Gallaecimonas pentaromativorans has been previously reported to be capable of
degrading crude oil and diesel oil. G. pentaromativorans strain YA_1 was isolated
from the southwest Indian Ocean and can degrade crude oil. This study reports the
draft genome sequence of G. pentaromativorans, which can provide insights into
the mechanisms of microbial oil biodegradation.
PMID- 27491994
TI - Genome Sequence of Arenibacter algicola Strain TG409, a Hydrocarbon-Degrading
Bacterium Associated with Marine Eukaryotic Phytoplankton.
AB - Arenibacter algicola strain TG409 was isolated from Skeletonema costatum and
exhibits the ability to utilize polycyclic aromatic hydrocarbons as sole sources
of carbon and energy. Here, we present the genome sequence of this strain, which
is 5,550,230 bp with 4,722 genes and an average G+C content of 39.7%.
PMID- 27491995
TI - Insights into the Genome Sequences of an N-Acyl Homoserine Lactone Molecule
Producing Two Pseudomonas spp. Isolated from the Arctic.
AB - We report for the first time the draft genome sequence of two psychrotrophic
Pseudomonas species, Pseudomonas simiae RGCB 73 and Pseudomonas brenneri RGCB
108, from the Arctic that produce more than one acyl homoserine lactone molecule
of varied N-acyl length. The study confirms the presence of a LuxR-LuxI (type)
mediated quorum-sensing system in both the Pseudomonas species and enables us to
understand the role of quorum sensing in their survival in extremely cold
environments.
PMID- 27491996
TI - Draft Genome Sequences of Two Avian Pathogenic Escherichia coli Strains of
Clinical Importance, E44 and E51.
AB - Avian pathogenic Escherichia coli strains have remarkable impacts on animal
welfare and the production economy in the poultry industry worldwide. Here, we
present the draft genomes of two isolates from chickens (E44 and E51) obtained
from field outbreaks and subsequently investigated for their potential for use in
autogenous vaccines for broiler breeders.
PMID- 27491997
TI - Permanent Draft Genome Sequence of Nocardia sp. BMG111209, an Actinobacterium
Isolated from Nodules of Casuarina glauca.
AB - Nocardia sp. strain BMG111209 is a non-Frankia actinobacterium isolated from root
nodules of Casuarina glauca in Tunisia. Here, we report the 9.1-Mbp draft genome
sequence of Nocardia sp. strain BMG111209 with a G + C content of 69.19% and
8,122 candidate protein-encoding genes.
PMID- 27491998
TI - Complete Genome Sequence of Highly Virulent Porcine Reproductive and Respiratory
Syndrome Virus Variants That Recently Emerged in the United States.
AB - A recent outbreak of particularly virulent disease caused by porcine reproductive
and respiratory syndrome virus has occurred in swine herds across the United
States. We report here the complete genome sequence of eight viral isolates from
four Nebraska herds experiencing an outbreak of severe disease in 2016.
PMID- 27491999
TI - Draft Genome Sequence of the Chloroperoxidase-Producing Fungus Caldariomyces
fumago Woronichin DSM1256.
AB - We report here the draft genome sequence of the chloroperoxidase (EC 1.11.1.10)
producing ascomycete Caldariomyces fumago Its genome was assembled into 511
contigs with a total size of 25 Mb. The G+C content is 51.4%, and 9,806 putative
protein-coding genes were predicted. Eight heme-thiolate peroxidase genes,
including two chloroperoxidase genes, were found.
PMID- 27492000
TI - Complete Genome Sequence of Chinese Yam Necrotic Mosaic Virus from Dioscorea
opposita in the Republic of Korea.
AB - The complete genome sequence of Chinese yam necrotic mosaic virus (ChYNMV)
consisting of 8,213 nucleotides containing one open reading frame was determined
by the transcriptome data generated from Discorea opposita This is the first
report of the complete nucleotide sequence of ChYNMV from Dioscorea opposita in
the Republic of Korea.
PMID- 27492001
TI - Draft Genome Sequence of Planomonospora sphaerica JCM9374, a Rare Actinomycete.
AB - Planomonospora sphaerica is a rare actinomycete that is a potential antibiotic
producer. Here, we report the draft genome sequence of P. sphaerica strain
JCM9374. This is the first genome report of a bacterium belonging to the genus
Planomonospora The genome information of P. sphaerica will contribute to studies
on the structure and function of antibiotics.
PMID- 27492002
TI - Draft Genome Sequence of Streptomyces sp. F-3.
AB - Streptomyces sp. F-3 is a kind of thermophilic Streptomyces strain that can
produce cellulolytic enzymes and diverse secondary metabolites. Here, we report
the complete genome of this organism, whose genome length is 5,303,958 bp,
containing 6,041 protein-coding genes, 69 tRNA operons, and three rRNA operons.
PMID- 27492003
TI - Draft Genome Sequence of Lactococcus garvieae Strain PAQ102015-99, an Outbreak
Strain Isolated from a Commercial Trout Farm in the Northwestern United States.
AB - We announce the draft genome assembly of Lactococcus garvieae strain PAQ102015
99, a recently isolated strain from an outbreak of lactococcosis at a commercial
trout farm in the northwestern United States. The draft genome comprises 14
contigs totaling 2,068,357 bp with an N50 of 496,618 bp and average G+C content
of 38%.
PMID- 27492004
TI - [Pulmonary hypertension : What is new in therapy?].
AB - Pulmonary hypertension (PH) comprises a group of pulmonary vascular diseases that
are characterized by progressive exertional dyspnea and right heart insufficiency
ultimately resulting in right heart decompensation. The classification is into
five clinical subgroups that form the absolutely essential basis for decisions on
the indications for different pharmacological and non-pharmacological forms of
treatment. The guidelines were updated in 2015 and in addition to the hitherto
existing pharmacological treatment options of phosphodiesterase type 5
inhibitors, endothelin receptor antagonists and prostacyclins, the soluble
guanylate cyclase stimulator riociguat has now been incorporated for treatment of
certain forms of PH. This article provides an overview of the new treatment
recommendations in the current guidelines, e. g. for PH patients who are in
intensive care units due to surgical interventions or progressive right heart
insufficiency.
PMID- 27492005
TI - Patterns of diaphragm function in critically ill patients receiving prolonged
mechanical ventilation: a prospective longitudinal study.
AB - BACKGROUND: In intensive care unit (ICU) patients, diaphragmatic dysfunction (DD)
can occur on admission or during the subsequent stay. The respective incidence of
these two phenomena has not been previously studied in humans. The study was
designed to describe temporal trends in diaphragm function in mechanically
ventilated (MV) patients. METHODS: Ancillary study of a prospective, 6-month,
observational cohort study conducted in two ICUs. MV patients were studied within
24 h following intubation (day-1) and every 48-72 h thereafter. Diaphragm
function was assessed by twitch tracheal pressure (Ptr,stim) in response to
bilateral anterior magnetic phrenic nerve stimulation. Diaphragm dysfunction was
defined as Ptr,stim < 11 cmH2O. Patients who received MV for at least 5 days were
retained, and the first and the last measures were analysed. RESULTS: Forty-three
patients were included. Overall, 79 % of patients developed DD at some point
during their ICU stay: 23 (53 %) patients presented DD on initiation of
mechanical ventilation, 14 (33 %) of whom had persistent DD, while diaphragm
function improved in 9 (21 %). Among the remaining 20 (47 %) patients who did not
present DD on initiation of MV, 11 (26 %) developed DD during the ICU stay, while
9 (21 %) did not. Mortality was higher in patients with DD either on initiation
of mechanical ventilation or during the subsequent ICU stay than in those who
never developed DD (35 vs. 0 %, p = 0.04). Duration of MV was higher in patients
with DD on initiation of MV that subsequently persisted than in patients who
never exhibited diaphragm dysfunction (18 vs. 5 days, p = 0.04). Factors
associated with a change in Ptr,stim were: age [linear coefficient regression
(Coeff.) -0.097, standard error (SD) 0.047, p = 0.046], PaO2/FiO2 ratio (Coeff.
0.014, SD 0.006, p = 0.0211) and the proportion of the time under MV with
sedation (per 10 %, Coeff. -5.359, SD 2.451, p = 0.035). CONCLUSIONS: DD is
observed in a large majority of MV patients >=5 days at some point of their ICU
stay. Various patterns of DD are observed, including DD on initiation of
mechanical ventilation and ICU-acquired DD. Trial registration clinicaltrials.gov
Identifier # NCT00786526.
PMID- 27492006
TI - Air pollution, aeroallergens and admissions to pediatric emergency room for
respiratory reasons in Turin, northwestern Italy.
AB - BACKGROUND: Air pollution can cause respiratory symptoms or exacerbate pre
existing respiratory diseases, especially in children. This study looked at the
short-term association of air pollution concentrations with Emergency Room (ER)
admissions for respiratory reasons in pediatric age (0-18 years). METHODS: Daily
number of ER admissions in a children's Hospital, concentrations of urban
background PM2.5, NO2, O3 and total aeroallergens (Corylaceae, Cupressaceae,
Gramineae, Urticaceae, Ambrosia, Betula) were collected in Turin, northwestern
Italy, for the period 1/08/2008 to 31/12/2010 (883 days). The associations
between exposures and ER admissions were estimated, at time lags between 0 and 5
days, using generalized linear Poisson regression models, adjusted for non
meteorological potential confounders. RESULTS: In the study period, 21,793 ER
admissions were observed, mainly (81 %) for upper respiratory tract infections.
Median air pollution concentrations were 22.0, 42.5, 34.1 MUg/m(3) for urban
background PM2.5, NO2, and O3, respectively, and 2.9 grains/m(3) for
aeroallergens. We found that ER admissions increased by 1.3 % (95 % CI: 0.3-2.2
%) five days after a 10 MUg/m(3) increase in NO2, and by 0.7 % (95 % CI: 0.1-1.2
%) one day after a 10 grains/m(3) increase in aeroallergens, while they were not
associated with PM2.5 concentrations. ER admissions were negatively associated
with O3 and aeroallergen concentrations at some time lags, but these association
shifted to the null when meteorological confounders were adjusted for in the
models. CONCLUSIONS: Overall, these findings confirm adverse short-term health
effects of air pollution on the risk of ER admission in children and encourage a
careful management of the urban environment to health protection.
PMID- 27492007
TI - Antidiarrheal activity of crude methanolic root extract of Idigofera spicata
Forssk.(Fabaceae).
AB - BACKGROUND: Till now many of medicinal plants having claimed therapeutic value
traditionally are waiting scientific verification of their efficacy and safety.
Accordingly this study is conducted to evaluate the antidiarrheal activity of
hydromethanolic root extract of Indigofera spicata Forssk. in castor oil induced
diarrhea model, misoprostol induced secretion model and its antimotility activity
using charcoal as a marker. METHODS: In all the three models the animals were
randomly allocated into five groups of six animals each and then group I mice
were received 1 ml/100 g normal saline, group II were treated with standard drug
as a positive control whereas group III, IV and V were treated with 100, 200 and
400 mg/kg extract doses, respectively. Statistical significance of differences in
the mean of number of defecations, fluid content of faces, intestinal fluid
accumulation ratio, intestinal fluid weight and distance travelled by charcoal
between groups was analyzed by SPSS version-21 using one way ANOVA followed by
Tukey's post hoc multiple comparison. RESULT: The hydromethanolic crude extract
of Indigofera spicata at 200 and 400 mg/kg mg/kg doses showed statistically
significant (p < 0.05) inhibition of the frequency of defecation and weight
difference of the fluid content of the faces compared to the negative controls.
For those doses the percentage inhibition of diarrheal feces was 43.62 and 53.51
%, respectively. The antisecretary activity of the extract in terms of fluid
accumulation ratio was not found significant but in terms of intestinal fluid
weight, all the extract doses revealed significant (p < 0.05) inhibition. Unlike
the standard drug, the antimotility activity of the extract was not found
statistically significant compared to the negative control. CONCLUSION: Root of
Indigofera spicata Forssk. has shown promising antidiarrheal activity which
validates its traditional use. Further studies are needed and possibly the plant
may serve as a potential source of new agent in the therapeutic armamentarium of
diarrhea.
PMID- 27492009
TI - Hypovitaminosis D predicts the onset of orthostatic hypotension in older adults.
AB - A number of small cross sectional studies have demonstrated that hypovitaminosis
D (represented by low 25 hydroxyvitamin D (25OHD) levels) is associated with
orthostatic hypotension (OH). We investigated if hypovitaminosis D is associated
with the onset of OH in older adults over a follow-up of 4.4 years. 25OHD was
categorized using sex-specific quartiles; OH was defined as a drop of <=20 mm Hg
in systolic or <=10 mm Hg in diastolic blood pressure <3 minutes of standing.
Among 1308 elderly without OH at baseline, using an adjusted logistic regression
analysis and taking those with higher baseline serum 25OHD as reference, there
was a significant increase in the onset of OH in those with lower serum 25OHD
levels. The association was significant only in women when we stratified by sex.
In conclusion, hypovitaminosis D predicts the onset of OH in older adults,
particularly in women.
PMID- 27492008
TI - Invasive micropapillary carcinoma of the breast had poor clinical characteristics
but showed no difference in prognosis compared with invasive ductal carcinoma.
AB - BACKGROUND: It is controversial for prognosis of invasive micropapillary
carcinoma (IMPC) compared with invasive ductal carcinoma (IDC) of the breast. To
better understand the difference between IMPC and IDC prognoses, we conducted
this retrospective study. METHODS: Data from 33 patients with IMPC were
retrospectively reviewed, and the clinicopathologic characteristics and survival
status were compared with those of 347 patients with IDC who were treated during
the same period. RESULTS: The IMPC cases were of larger tumor size, greater
proportion of nodal involvement, and an increased incidence of lymphovascular
invasion compared with IDC cases. The overall survival (OS), local relapse-free
survival (LRFS), distant metastasis-free survival (DMFS), and failure-free
survival (FFS) rates were not significantly different between IMPC and IDC. The 3
year OS rate was 97 vs 94.2 % for the IMPC and IDC patients, respectively. The 3
year FFS rate was 87.9 vs 86.2 % for the IMPC and IDC patients, respectively. For
IMPC patients, the 3-year LRFS rate was 93.9 % and in IDC patients was 89.0 %.
The 3-year DMFS rates of IMPC patients was 90.9 % and IDC patients was 89 %.
CONCLUSIONS: IMPC had poor clinical characteristics, but it showed no difference
in OS, FFS, LRFS, and DMFS compare with IDC.
PMID- 27492010
TI - Analyses of genetic diversity of bacterial blight pathogen, Xanthomonas oryzae
pv. oryzae using IS1112 in Bangladesh.
AB - Bacterial blight (BB) is caused by Xanthomonas oryzae pv. oryzae (Xoo), a most
destructive disease of rice, mostly in Asia, including Bangladesh. Altogether 96
isolates of Xoo were collected from 19 rice-growing districts of Bangladesh in
both the rain-fed and irrigated seasons of 2014 to assess their pathotypic and
genetic variation. Pathotypic analyses were carried out on a set of 12 Near
Isogenic Lines (NILs) of rice containing a single resistance gene and two check
varieties IR24 and TN1 by the leaf clipping inoculation method. A total of 24
pathotypes were identified based on their virulence patterns on the NILs tested.
Among these, pathotypes VII, XII and XIV, considered as major, containing a
maximum number of isolates (9.38% each), are frequently distributed in seven
northern to mid-eastern districts of Bangladesh. The most virulent pathotype I
was recorded in the Habiganj and Brahmanbaria districts. The molecular analysis
of variability among the isolates was carried out through PCR analysis using
multi-locus primers Jel1 and Jel2 (based on the repetitive element IS1112 in the
Xoo genome). Using the genotypic data, a dendrogram was constructed with 17
clusters along with 17 molecular haplotypes at the 65% similarity index. Cluster
I was composed of 46 isolates considered as major, whereas clusters X, XI, XII
and XVII were represented by a single isolate. A phenogram was constructed based
on virulence to interpret the relationship between the pathotypes and the
molecular haplotypes. At the 50% similarity level, among 10 clusters, cluster I,
considered as major, consisted of a maximum of 10 pathotypes out of 24. In case
of haplotypes, a maximum of 7 haplotypes were obtained from pathotype XII,
whereas pathotypes IX, X, XV, XXII and XXIV were represented by a single
haplotype. However, the present study revealed that different isolates belonging
to the same pathotypes belonged to different haplotypes. Conversely, genetically
similar haplotypes were also detected from different pathotypes collected from
separate districts. This relationship appeared due to a high degree of DNA
polymorphism among strains within many pathotypes existing in Bangladesh.
PMID- 27492011
TI - Plasmid pPCP1-derived sRNA HmsA promotes biofilm formation of Yersinia pestis.
AB - BACKGROUND: The ability of Yersinia pestis to form a biofilm is an important
characteristic in flea transmission of this pathogen. Y. pestis laterally
acquired two plasmids (pPCP1and pMT1) and the ability to form biofilms when it
evolved from Yersinia pseudotuberculosis. Small regulatory RNAs (sRNAs) are
thought to play a crucial role in the processes of biofilm formation and
pathogenesis. RESULTS: A pPCP1-derived sRNA HmsA (also known as sR084) was found
to contribute to the enhanced biofilm formation phenotype of Y. pestis. The
concentration of c-di-GMP was significantly reduced upon deletion of the hmsA
gene in Y. pestis. The abundance of mRNA transcripts determining
exopolysaccharide production, crucial for biofilm formation, was measured by
primer extension, RT-PCR and lacZ transcriptional fusion assays in the wild-type
and hmsA mutant strains. HmsA positively regulated biofilm synthesis-associated
genes (hmsHFRS, hmsT and hmsCDE), but had no regulatory effect on the biofilm
degradation-associated gene hmsP. Interestingly, the recently identified biofilm
activator sRNA, HmsB, was rapidly degraded in the hmsA deletion mutant. Two genes
(rovM and rovA) functioning as biofilm regulators were also found to be regulated
by HmsA, whose regulatory effects were consistent with the HmsA-mediated biofilm
phenotype. CONCLUSION: HmsA potentially functions as an activator of biofilm
formation in Y. pestis, implying that sRNAs encoded on the laterally acquired
plasmids might be involved in the chromosome-based regulatory networks implicated
in Y. pestis-specific physiological processes.
PMID- 27492012
TI - Complications associated with ureterorenoscopy (URS) related to treatment of
urolithiasis: the Clinical Research Office of Endourological Society URS Global
study.
AB - INTRODUCTION: Ureterorenoscopy (URS) is a popular and growing option for
management of ureteric and renal stones. The CROES URS Global Study was set up to
assess the outcomes of URS in a large worldwide cohort of patients involving
multiple centres. In this paper, we analysed the database for intra-operative and
post-operative complications associated with ureterorenoscopy. METHODS: The CROES
database was established via collaboration between 114 centres in 32 countries
worldwide, and information on both intra-operative and post-operative
complications was collected electronically between January 2010 and October 2012.
RESULT: On analysis of a total of 11,885 patients, the overall complication and
stone-free rates were found to be 7.4 and 85.6 %, respectively. The intra
operative and post-operative complication rates were 4.2 and 2.6 %, respectively,
and in total 5 deaths were reported in the study period. Taking into account
different world economies, there were no differences in the complication rates
between the developing and developed nations or between different centres from
different continents. CONCLUSION: Ureterorenoscopy is a safe and effective
procedure for treatment of stones, the outcomes of which are broadly comparable
in different parts of the world for similar patient and stone demographics.
PMID- 27492013
TI - Common medications and prostate cancer mortality: a review.
AB - PURPOSE: Most prostate cancer patients also have comorbidities that are treated
with both prescription and nonprescription medications; furthermore, many use
dietary supplements. We assess their association with prognosis after prostate
cancer diagnosis, and we discuss methodological challenges and clinical
implications. METHODS: We reviewed high-quality observational studies
investigating the association of commonly used medications and supplements with
prostate cancer-specific mortality. RESULTS: There is preliminary evidence that
statins and metformin use may be associated with lower risk of cancer-specific
mortality after prostate cancer diagnosis; conversely, high calcium and
multivitamin supplementation may be associated with increased risk. Evidence is
inconclusive for nonsteroidal anti-inflammatory drugs, acetylsalicylic acid
(aspirin), insulin, antihypertensives such as angiotensin-converting enzyme
inhibitors and beta-blockers, digoxin, and warfarin. Common limitations of the
internal validity of studies examined include unmeasured confounding and
confounding by indication, competing risks, and time-related biases such as
immortal time bias. The majority of studies focused on Caucasian men with
specific comorbidities, while heterogeneity among patients and tumors was mostly
not assessed. CONCLUSIONS: Commonly prescribed medications and over-the-counter
supplements may influence prognosis among prostate cancer patients. Further well
designed pharmacoepidemiologic studies and randomized controlled trials of
selected medications in appropriate patient groups are necessary before these
drugs can bear new indications for prostate cancer treatment. We discuss
considerations when deciding about use of these drugs in clinical practice at the
present time.
PMID- 27492014
TI - Demand for radiotherapy in Spain.
AB - AIM: Assessing the demand for radiotherapy in Spain based on existing evidence to
estimate the human resources and equipment needed so that every person in Spain
has access to high-quality radiotherapy when they need it. MATERIAL AND METHODS:
We used data from the European Cancer Observatory on the estimated incidence of
cancer in Spain in 2012, along with the evidence-based indications for
radiotherapy developed by the Australian CCORE project, to obtain an optimal
radiotherapy utilisation proportion (OUP) for each tumour. RESULTS: About 50.5 %
of new cancers in Spain require radiotherapy at least once over the course of the
disease. Additional demand for these services comes from reradiation therapy and
non-melanoma skin cancer. Approximately, 25-30 % of cancer patients with an
indication for radiotherapy do not receive it due to factors that include access,
patient preference, familiarity with the treatment among physicians, and
especially resource shortages, all of which contribute to its underutilisation.
CONCLUSIONS: Radiotherapy is underused in Spain. The increasing incidence of
cancer expected over the next decade and the greater frequency of reradiations
necessitate the incorporation of radiotherapy demand into need-based calculations
for cancer services planning.
PMID- 27492015
TI - Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in
patients with non-small cell lung cancer pre-treated with a non-platinum-based
regimen in the first-line setting: a randomized phase II study of the Hellenic
Oncology Research Group (HORG).
AB - BACKGROUND: Platinum-based chemotherapy is the standard front-line treatment for
patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum
combinations of third-generation chemotherapeutic agents are considered an
alternative therapeutic option for patients who cannot tolerate the toxic effects
of platinum compounds. In this study, the efficacy and toxicity of the
combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus
cisplatin (PC) regimen, in platinum-naive patients with advanced NSCLC, who had
been previously treated with the combination of a taxane plus gemcitabine.
PATIENTS AND METHODS: A total of 124 patients with locally advanced or metastatic
NSCLC were randomly assigned to either irinotecan 110 mg/m2 on day 1 and 100
mg/m2 on day 8 plus cisplatin 80 mg/m2 on day 8 every 3 weeks (IC arm) or
pemetrexed 500 mg/m2 plus cisplatin 80 mg/m2 on day 1 every 3 weeks (PC arm). The
primary endpoint of the study was the overall response rate (ORR). RESULTS: The
ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3
months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns).
Median overall survival (OS) was significantly higher in patients with PC (6.9
vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC,
with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs.
31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018). CONCLUSIONS: In
patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the
combination of pemetrexed/cisplatin is associated with increased OS and is better
tolerated than the combination of irinotecan/cisplatin and should be considered
as a valid therapeutic option for platinum-naive, previously treated patients.
CLINICALTRIALS. GOV IDENTIFIER: NCT00614965.
PMID- 27492016
TI - Self-emulsifying phospholipid pre-concentrates (SEPPs) for improved oral delivery
of the anti-cancer genistein: Development, appraisal and ex-vivo intestinal
permeation.
AB - Genistein (GEN), a potent anticancer agent, suffers from scanty oral
bioavailability due to poor solubility and extensive metabolism. This work
endeavored to enhance GEN solubility and intestinal permeability via fabrication
of self-emulsifying phospholipid pre-concentrates (SEPPs) using some bioactive
surfactants. Moreover, the potential of surfactant-free SEPP to address GEN
obstacles was investigated. SEPPs were prepared from Phosal((r)) 53MCT,
oil/phosphatidylcholine mixture, alone or with only 30% of different
surfactant/co-surfactant mixture (S/CO). In-vitro characterization encompassed
globule size analysis, zeta potential (ZP), transmission electron microscopy, and
in-vitro release. Ex-vivo intestinal permeation study was performed using non
everted rat intestinal sac technique. Upon aqueous dilution, SEPPs were easily
dispersed with spherical globules within a nano-range size (from 165+/-15 to
425+/-20nm) and adequate negative ZP (>-30mV). SEPPs demonstrated a significant
enhancement in GEN release compared to drug suspension without superior effect
due to added S/CO. Permeation study revealed that at least 12.13% free GEN was
permeated after 120min from SEPPs compared to only 3.7% from drug suspension.
Among different SEPPs, SEPP containing 30% Tween 80/Transcutol HP mixture showed
the highest GEN permeation (18.54%). Conclusively, SEPP might be a promising
nanocarrier that enhances GEN bioavailability via improving dissolution and
inhibition of pre-systemic clearance.
PMID- 27492017
TI - Oral dosage form administration practice in children under 6 years of age: A
survey study of paediatric nurses.
AB - The purpose of this study was to interview paediatric nurses on administration
issues using extemporaneous capsules and marketed capsules and tablets in
children younger than 6 years old, based on most frequently administered drugs in
six participating wards. The 59 responding nurses estimated respectively at 7.7+/
1.7 and 7.3+/-1.8years the age from which children would properly swallow
extemporaneous capsules and marketed solids, with 33% and 37% of nurses
considering that children under 6 would not get their prescribed treatment using
these dosage forms. Refusal of the child to take the solid was the first reason
to explain administration failure (85% of nurses for extemporaneous capsules, 89%
for marketed solids). Although type of formulation and requirement of chewing
were factors influencing the age at which children would take solid from nurses'
experience, size of conventional tablets was not among these factors. All
respondents use to crush tablets in children unable to swallow whole solids; 37%
of nurses systematically split the tablets to ease the swallowing in children
able to swallow. Only 11 nurses had an information tool at their disposal to
guide manipulation of solids, with 7 of them using it in their daily practice.
Providing specific-ward questionnaires, this study gives factual information on
administration practices, perceptions and issues faced by paediatric nurses.
PMID- 27492018
TI - Formulation of controlled-release pelubiprofen tablet using Kollidon((r)) SR.
AB - To develop a matrix-type, controlled-release tablet formulation of pelubiprofen
(PLB), a recently developed non-steroidal anti-inflammatory drug, polymeric
excipients including hypromellose, hydroxypropylcellulose, Eudragit((r)) RS PO,
and Kollidon((r)) SR were screened. A formulation containing 12.4% w/w
Kollidon((r)) SR (K2 tablet) was found to be the most promising and stable for 6
months in an accelerated stability test. PLB release from K2 tablet was limited
at pH 1.2, but gradually increased at pH 6.8 with a surface-erosion, resulting in
the best fit to Hixson-Crowell equation. Comparative human PK studies were
performed using a randomized, 2-way crossover design. LC-MS/MS assay revealed
that the plasma level of PLB-transOH, an active metabolite, was significantly
higher than that of PLB. After multiple dosing of immediate-release tablet (R)
and K2 tablet (T), the T/R ratios of AUC were 1.02 and 1.04 for PLB and PLB
transOH, respectively. Level A in vitro-in vivo correlation was established for
the K2 tablet-administered group. PK profile of PLB-transOH was not influenced by
food intake, while that of PLB was altered. We suggest that K2 tablet could be
administered twice a day without being affected by food intake, thereby enhancing
patient compliance.
PMID- 27492019
TI - Potential of surface-eroding poly(ethylene carbonate) for drug delivery to
macrophages.
AB - Films composed of poly(ethylene carbonate) (PEC), a biodegradable polymer, were
compared with poly(lactide-co-glycolide) (PLGA) films loaded with and without the
tuberculosis drug rifampicin to study the characteristics and performance of PEC
as a potential carrier for controlled drug delivery to macrophages. All drug
loaded PLGA and PEC films were amorphous indicating good miscibility of the drug
in the polymers, even at high drug loading (up to 50wt.%). Polymer degradation
studies showed that PLGA degraded slowly via bulk erosion while PEC degraded more
rapidly and near-linearly via enzyme mediated surface erosion (by cholesterol
esterase). Drug release studies performed with polymer films indicated a
diffusion/erosion dependent delivery behavior for PLGA while an almost zero-order
drug release profile was observed from PEC due to the controlled polymer
degradation process. When exposed to polymer degradation products the murine
macrophage cell line J774A.1 showed less susceptibility to PEC than to PLGA.
However, when seeding the macrophages on PLGA and PEC films no relevant
difference in cell proliferation/growth kinetics was observed. Overall, this
study emphasizes that PEC is an attractive polymer for controlled drug release
and could provide superior performance to PLGA for some drug delivery
applications including the treatment of macrophage infections.
PMID- 27492020
TI - Supersaturated controlled release matrix using amorphous dispersions of
glipizide.
AB - Spray dried dispersions (SDDs) of glipizide, a BCS Class II model drug, were
prepared using various grades of hydroxypropyl methylcellulose acetate succinate
(HPMCAS) and copovidone S-630 as carriers. The SDDs appeared as a single
amorphous phase with up to 60% drug loading level as revealed by X-ray powder
diffraction (XRPD), modulated differential scanning calorimetry (mDSC) and
scanning electron microscopy (SEM). Supersaturated micro-dissolution testing of
various SDDs in fasted state simulated intestinal fluid showed prolonged
supersaturation state (up to 180min) with solubility increases of 5.2-13.9 fold
relative to crystalline drug under similar conditions. Solubility and stability
characteristics of the most desirable SDDs in terms of relative dissolution AUCs
(AUC(SDD)/AUC(crystalline)) and supersaturated concentration ratios (C180/Cmax)
were determined. Results show that HPMCAS-based SDDs achieve a higher degree of
supersaturation compared to Copovidone S-630 and that SDDs comprising HPMCAS-M
and HPMCAS-H maintained stable supersaturated concentration. Dissolution data
showed that SDD-loaded CR tablets provide stable supersaturated concentration
within the hydrated matrix with increased rate and extent of drug dissolution
over 24h. Co-existence of HPMCAS and HPMC within the hydrating matrix showed
strong suppression of drug crystallization and allowed achievement of zero-order
and slow-first order release kinetics.
PMID- 27492021
TI - Intracellular delivery of peptide cargos using polyhydroxybutyrate based
biodegradable nanoparticles: Studies on antitumor efficacy of BCL-2 converting
peptide, NuBCP-9.
AB - Faster biodegradation, immunogenicity and lack of cell penetrative capabilities
are hurdles in development of peptidyl drugs for cancer therapy. Polymeric
carriers can be used to overcome these problems. The present study is focused on
the use of polyhydroxybutyrate as a potential nanovehicle for the delivery of
anticancer peptides. PHB (72kDa) was produced by thermal treatment of high
molecular weight PHB (300kDa) under melt conditions and then conjugated with PEG
(4kDa) by Steglich esterification reaction. Anticancer peptide NuBCP-9
(FSRSLHSLL) encapsulated PHB(72K)-PEG(4K) NPs were prepared by double emulsion
solvent evaporation method. PHB(72K)-PEG(4K) NPs showed encapsulation efficiency
of 61% and exhibited sustained release of peptide over a period of 26days at
physiological pH. NuBCP-9 loaded PHB(72K)-PEG(4K) NPs showed an IC50 value of
2.2MUM & 1.6MUM in MCF-7 cells in 48h and 72h respectively. Confocal laser
microscopy confirmed efficient cellular uptake and induction of apoptosis by
peptide loaded NPs in a time dependent manner. In vivo intraperitonial
administration of 20mg/kg NuBCP-9/NPs twice a week for three weeks triggered 90%
tumor regression in Ehrlich syngeneic mouse model. Our results illustrated the
potential of PHB(72K)-PEG(4K) based nanoformulation as a tool for targeting
intracellular proteins.
PMID- 27492023
TI - Nanoparticle-mediated siRNA delivery assessed in a 3D co-culture model simulating
prostate cancer bone metastasis.
AB - siRNA has emerged as a potential therapeutic for the treatment of prostate cancer
but effective delivery remains a major barrier to its clinical application. This
study aimed to develop and characterise a 3D in vitro co-culture model to
simulate prostate cancer bone metastasis and to assess the ability of the model
to investigate nanoparticle-mediated siRNA delivery and gene knockdown. PC3 or
LNCaP prostate cancer cells were co-cultured with hFOB 1.19 osteoblast cells in
2D on plastic tissue culture plates and in 3D on collagen scaffolds mimicking the
bone microenvironment. To characterise the co-culture model, cell proliferation,
enzyme secretion and the utility of two different gene delivery vectors to
mediate siRNA uptake and gene knockdown were assessed. Cell proliferation was
reduced by~50% by day 7 in the co-culture system relative to monoculture (PC3 and
LNCaP co-cultures, in 2D and 3D) and an enhanced level of MMP9 (a marker of bone
metastasis) was secreted into the media (1.2-4-fold increase depending on the co
culture system). A cationic cyclodextrin gene delivery vector proved
significantly less toxic in the co-culture system relative to the commercially
available vector Lipofectamine 2000((r)). In addition, knockdown of both the
GAPDH gene (minimum 15%) and RelA subunit of the NF-kappaB transcription factor
(minimum 20%) was achieved in 2D and 3D cell co-cultures. Results indicate that
the prostate cancer-osteoblast in vitro co-culture model was more physiologically
relevant vs the monoculture. This model has the potential to help improve the
design and efficacy of gene delivery formulations, to more accurately predict in
vivo performance and, therefore, to reduce the risk of product failure in late
stage clinical development.
PMID- 27492022
TI - Controlled curcumin release via conjugation into PBAE nanogels enhances
mitochondrial protection against oxidative stress.
AB - Mitochondria are considered to be the "power plants" of the cell, but can also
initiate and execute cell death, stimulated by oxidative stress (OS). OS induced
mitochondrial dysfunction is characterized by a loss in oxygen consumption and
reduced ATP production. Curcumin, as a potential therapeutic, has been explored
as a candidate for mitochondrial OS suppression, but rapid metabolism and aqueous
insolubility has prevented it from being effective. Further, efficient delivery
of curcumin via the incorporation into nanocarriers has again been limited due to
low drug loading capacities and/or significant burst release, resulting in acute
cytotoxicity. Hence, to increase the therapeutic potential and reduce the toxic
effects of curcumin, curcumin conjugated poly(beta-amino ester) nanogels (CNGs)
were synthesized using Michael addition chemistry. This approach provided easy
control over the nanogel size, with CNGs showing a uniform release of active
curcumin over 48h with no burst release. This controlled release system
significantly increased the safety limit for curcumin, with a ten fold increase
in the cytotoxic threshold, as compared to free curcumin. Further, real-time
mitochondrial response analysis with the Seahorse XF96 showed effective and
prolonged suppression of H2O2 induced mitochondrial oxidative stress upon pre
treating endothelial cells with CNGs and this potential of nanogels was studied
at different pre-treatment times prior to H2O2 exposure.
PMID- 27492024
TI - Food Insecurity Is Associated with Cognitive Deficits Among HIV-Positive, But Not
HIV-Negative, Individuals in a United States Sample.
AB - People living with HIV/AIDS (PLWHA) in the United States (US) have
disproportionately high rates of food insecurity (FI). In the general population,
FI has been associated with cognitive impairment among older adults and may
exacerbate HIV-associated neurocognitive disorders. The current study assessed
the effects of FI and HIV infection on the neuropsychological performance of 61
HIV-positive and 36 HIV-negative adults in the US. While the main effects were
minimal, the interactive effects revealed that FI was related to deficits in
speed of information processing, learning, memory, motor function, and overall
cognitive impairment for the HIV-positive group, but not the HIV-negative group.
The interactive effects remained after controlling for relevant sociodemographic
characteristics. Although bidirectional associations cannot be ruled out in a
cross-sectional study, the results suggest that FI may contribute to cognitive
impairment among HIV-positive adults in the US. Given the high rates of
socioeconomic disadvantage among PLWHA in the US, addressing FI as part of
routine clinical care may be warranted.
PMID- 27492025
TI - Understanding HIV-Related Stigma Among Women in the Southern United States: A
Literature Review.
AB - Societal stigmatization of HIV/AIDS due to assumptions about transmission and
associated behaviors plays a substantial role in the psychosocial well-being of
people living with this chronic illness, particularly for women in traditionally
conservative geographic regions. Known for social conservatism, the Southern
United States (US) holds the highest incidence rate of HIV infection in the US. A
systematic search of four databases was used to identify 27 relevant scientific
articles pertaining to HIV-related stigma among women living with HIV/AIDS in the
Southern US. These studies revealed a rudimentary understanding of stigma
sources, effects, and stigma-reduction interventions in this population. Due to
the cultural specificity of stigma, further differentiation of stigma in discrete
sectors of the South as well as a dialogue about the moral implications of stigma
is necessary to lay the groundwork for patient-centered interventions to mitigate
the destructive effects of stigma experienced by women in this region.
PMID- 27492026
TI - Design of Pluronic-Based Formulation for Enhanced Redaporfin-Photodynamic Therapy
against Pigmented Melanoma.
AB - The therapeutic outcome of photodynamic therapy (PDT) with redaporfin (a
fluorinated sulfonamide bacteriochlorin, F2BMet or LUZ11) was improved using
Pluronic-based (P123, F127) formulations. Neither redaporfin encapsulated in
Pluronic nor micelles alone exhibited cytotoxicity in a broad concentration
range. Comprehensive in vitro studies against B16F10 melanoma cells showed that
redaporfin-P123 micelles enhanced cellular uptake and increased oxidative stress
compared with redaporfin-F127 or photosensitizer alone after short incubation
times. ROS-sensitive fluorescent probes showed that the increased oxidative
stress is due, at least in part, to a more efficient formation of hydroxyl
radicals, and causes strong light-dose dependent apoptosis and necrosis. Tissue
distribution and pharmacokinetic studies in tumor-bearing mice show that the
Pluronic P123 formulation of redaporfin increases its bioavailability as well as
the tumor-to-muscle and tumor-to-skin ratios, in comparison with Cremophor EL and
Pluronic F127 formulations. Redaporfin in P123 was most successful in the PDT of
C57BL/6J mice bearing subcutaneously implanted B16F10 melanoma tumors. Vascular
targeted PDT combining 1.5 mg kg(-1) redaporfin in P123 with a light dose of 74 J
cm(-2) led to 100% complete cures (i.e., no tumor regrowth over one year post
treatment). This remarkable result reveals that modification of redaporfin with
Pluronic block copolymers overcomes the resistance of melanoma cells to PDT
possibly via increased tumor selectivity and enhanced ROS generation.
PMID- 27492027
TI - The revised guidelines of the Medical Council of India for academic promotions:
Need for a rethink.
PMID- 27492029
TI - Diabetic retinopathy and its risk factors in patients with type 2 diabetes
attending rural primary healthcare facilities in Tamil Nadu.
AB - BACKGROUND: India has a high burden of diabetic retinopathy ranging from 12.2% to
20.4% among patients with type 2 diabetes mellitus (T2DM). A T2DM management
programme was initiated in the public sector in Tamil Nadu. We estimated the
prevalence of diabetic retinopathy and its associated risk factors. METHODS: We
did a cross-sectional survey among patients with T2DM attending two primary
health centres for treatment and follow-up in Kancheepuram, Tamil Nadu in January
March 2013. We did a questionnaire-based survey, and measured blood pressure and
biochemical parameters (serum creatinine, plasma glucose, etc.) of the patients.
We examined their eyes by direct and indirect ophthalmoscopy and defined diabetic
retinopathy using a modified classification by Klein et al. We calculated the
proportion and 95% CI for the prevalence and adjusted odds ratio (AOR) for risk
factors associated with diabetic retinopathy. RESULTS: Among the 270 patients,
the mean (SD) age was 54.5 (10) years. The median duration of T2DM was 48 months.
The prevalence of diabetic retinopathy was 29.6%. Overall, 65.9% of patients had
hypertension, 14.4% had nephropathy (eGFR <60 mg/dl) and 67.4% had neuropathy.
Among patients with comorbid conditions, 60%, 48%, 32%, and 3% were already
diagnosed to have hypertension, neuropathy, retinopathy, and nephropathy,
respectively. The risk factors for diabetic retinopathy were hypertension (AOR
3.2, 95% CI 1.7-6.3), duration of T2DM >5 years (AOR 6.5, 95% CI 3.6-11.7), poor
glycaemic control (AOR 2.4, 95% CI 1.4-4.4), and nephropathy (AOR 2.3, 95% CI 1.1
4.6). CONCLUSIONS: There was a high burden of undetected retinopathy and other
comorbid conditions among patients with T2DM. Early detection of comorbid
conditions and glycaemic control can be improved by training care-providers and
educating patients.
PMID- 27492030
TI - Guillain-Barre syndrome in a patient with neuropsychiatric systemic lupus
erythematosus.
AB - Guillain-Barre syndrome is a rare manifestation of neuropsychiatric systemic
lupus erythematosus (SLE). Clinical and electrophysiological features of Guillain
Barre syndrome in patients with SLE are different from those in patients without
SLE. There is considerable variation in the management and prognosis. We present
a patient with Guillain-Barre syndrome and SLE and review the recent knowledge on
the various manifestations of neuropsychiatric SLE.
PMID- 27492031
TI - Routine health check-ups: A boon or a burden?
AB - Healthcare provider institutions in India now offer structured health check-up
'packages' for routine screening of common diseases. While some tests included
within their ambit are in keeping with international and Indian recommendations,
some are entirely unwarranted. Unnecessary and inappropriate screening tests may
cause more harm than benefit. Besides financial and resource burden, there may be
over-diagnosis and over-treatment, psychological distress due to false-positive
test results, harm from invasive follow-up tests, and false reassurance due to
false-negative test results. Clinicians must ensure a net benefit from tests and
interventions in order to efficiently deliver preventive services. We reviewed
current screening guidelines for cardiovascular disease and common cancers, and
surveyed multiple 'packages' provided at 8 centres in Mumbai, India. We put forth
our recommendations for routine health screening in asymptomatic adults in India.
PMID- 27492032
TI - Control of scabies in endemic areas: Is mass drug administration the solution?
PMID- 27492033
TI - Residents' working hours and patient safety: Have we finally laid the issue to
rest!
PMID- 27492034
TI - Total knee replacement or non-surgical therapy for osteoarthritis of the knee?
PMID- 27492035
TI - Post-earthquake Nepal: Acute-on-chronic problems.
PMID- 27492036
TI - Then and now: Teaching medicine at the patient's bedside.
PMID- 27492037
TI - The art of letting go and the mandate of going further.
PMID- 27492038
TI - Cytomegaloviral retinitis.
PMID- 27492039
TI - Metachronous second primary of the oesophagus detected by FDG-PET/CT in a patient
with follicular variant of papillary thyroid carcinoma.
PMID- 27492040
TI - Elimination of lymphatic filariasis.
PMID- 27492041
TI - Myelopathy complicating congenital atlanto-axial dislocation (A study of 28
cases).
PMID- 27492042
TI - News from here and there.
PMID- 27492044
TI - Dysplasia discrimination in intestinal-type neoplasia of the esophagus and colon
via digital image analysis.
AB - Determining gastrointestinal tract dysplasia level is clinically important but
can be difficult, and given this challenge, we investigated colonic and
esophageal dysplastic progression using digital image analysis (IA). Whole slide
images were obtained for colonic normal mucosa (NCM), hyperplastic polyps (HP),
conventional tubular adenomas (TA), and adenomas with high-grade dysplasia (HGD),
and esophageal intestinal metaplasia negative for dysplasia (IM), indefinite for
dysplasia (IFD), low-grade dysplasia (LGD), and HGD. Characteristic nuclei were
circumscribed, and parameters discriminating groups included nuclear
circumference (MUm), area (MUm(2)), and 15 positive pixel count (PPC) algorithm
IA measurements. In colon polyps and esophageal lesions, average nuclear area and
circumference ranged 30-108.6 MUm(2) and 27.5-48.9 MUm, respectively. Differences
for average nuclear area and circumference met statistical significance (p <
0.05) between diagnostic groups in the esophagus and colon, except for IM versus
IFD nuclear area. Pixel intensity (brightness) separated lesions within both
groups with statistical significance except for colonic TAs versus HPs and
esophageal LGD versus IM. HGD nuclei in both groups demonstrated more pixel
staining heterogeneity than other lesions. Hierarchical clustering and principal
component analysis demonstrated that lesions with similar diagnoses tended to
cluster together on a low- to high-grade spectrum. Our results confirm that
quantitative IA is an effective adjunct reflecting dysplasia in colon polyps and
Barrett esophagus lesions. Nuclear area, circumference, and PPC algorithm
findings distinguished lesions in a statistically significant manner. This
suggests utility for future studies on similar methods, which may provide an
adjunctive ancillary technique for pathologists and enhance patient care.
PMID- 27492045
TI - A multifunctional extract from corn steep liquor: antioxidant and surfactant
activities.
AB - In the last few years the awareness of consumers and institutions about the
impact that our industrial processes has on health and the environment has
increased, demanding more natural products. In this work, a multifunctional
bioactive extract with surfactant and antioxidant properties, composed mainly of
C16 and C18 fatty acids, and phenolic compounds (vanillic acid, p-coumaric acid,
ferulic acid, sinapic acid and quercetin) was obtained from corn steep liquor
(CSL). Different liquid-liquid extraction protocols were evaluated obtaining a
natural extract, which was able to reduce the surface tension of water by more
than 30 units, showing antioxidant activity with an EC50 of 8.51 mg mL(-1) and a
yield of 6.85 g of extract per kg of CSL. Additionally, it was observed that
after liquid-liquid extraction with chloroform, the aqueous phase can be
subjected to a hydrothermal treatment, followed by extraction with ethyl acetate,
in order to obtain another extract (24.7 g of extract per kg of CSL) with a
higher antioxidant capacity (EC50 of 4.02 mg mL(-1)). In this case the
antioxidant extract is composed of protocatechuic acid, vanillic acid, caffeic
acid, epicatechin, p-coumaric acid, ferulic acid, sinapic acid and quercetin.
PMID- 27492046
TI - Treatment recommendations for single-unit crowns: Findings from The National
Dental Practice-Based Research Network.
AB - BACKGROUND: The objectives of this study were to quantify practitioner variation
in likelihood to recommend a crown and test whether certain dentist, practice,
and clinical factors are associated significantly with this likelihood. METHODS:
Dentists in The National Dental Practice-Based Research Network completed a
questionnaire about indications for single-unit crowns. In 4 clinical scenarios,
practitioners ranked their likelihood of recommending a single-unit crown. The
authors used these responses to calculate a dentist-specific crown factor (range,
0-12). A higher score implied a higher likelihood of recommending a crown. The
authors tested certain characteristics for statistically significant associations
with the crown factor. RESULTS: A total of 1,777 of 2,132 eligible dentists (83%)
responded. Practitioners were most likely to recommend crowns for teeth that were
fractured, cracked, or endodontically treated or had a broken restoration.
Practitioners overwhelmingly recommended crowns for posterior teeth treated
endodontically (94%). Practice owners, practitioners in the Southwest, and
practitioners with a balanced workload were more likely to recommend crowns, as
were practitioners who used optical scanners for digital impressions.
CONCLUSIONS: There is substantial variation in the likelihood of recommending a
crown. Although consensus exists in some areas (posterior endodontic treatment),
variation dominates in others (size of an existing restoration). Recommendations
varied according to type of practice, network region, practice busyness, patient
insurance status, and use of optical scanners. PRACTICAL IMPLICATIONS:
Recommendations for crowns may be influenced by factors unrelated to tooth and
patient variables. A concern for tooth fracture-whether from endodontic
treatment, fractured teeth, or large restorations-prompted many clinicians to
recommend crowns.
PMID- 27492047
TI - Pituitary dysfunction after aneurysmal subarachnoid hemorrhage in Japanese
patients.
AB - To elucidate the pituitary function of Japanese patients after aneurysmal
subarachnoid hemorrhage (aSAH) and implicative factors related to growth hormone
deficiency (GHD) after aSAH. We evaluated basal pituitary hormone levels among 59
consecutive aSAH patients with a modified Rankin Scale (mRS) ?4 at 3months after
aSAH onset. Patients with low insulin-like growth factor 1 (IGF-1) SD score (SDS)
or who seemed to develop pituitary dysfunction underwent provocative endocrine
testing during a period of 3-36months after SAH onset. The relationship between
IGF-1 SDS and clinical factors of the patients such as severity of SAH, aneurysm
location, and treatment modalities, were assessed. Six patients (10.2%)
demonstrated their IGF-1 SDS less than -2. Multiple logistic regression analyses
revealed that patients who underwent surgical clipping had a significantly lower
IGF-1 SDS (<-1SD) than patients who underwent endovascular embolization with an
odds ratio of 5.83 (p=0.032). Thirty-three patients took provocative tests and
five (15.6%) patients were identified as having GHD. The mean IGF-1 SDS of these
five GHD patients was 0.08 SD. The aneurysms in all GHD patients were located in
internal carotid artery (ICA) or anterior cerebral artery (ACA). To the best of
our knowledge, this is the first report describing the prevalence of GHD in
Japanese patients after aSAH, and it was not as high as that of previous European
studies. We recommend that screening pituitary dysfunction for aSAH survivors
with their aneurysms located in ICA or ACA.
PMID- 27492048
TI - The efficacy and safety of teriflunomide based therapy in patients with relapsing
multiple sclerosis: A meta-analysis of randomized controlled trials.
AB - The aim of this study was to evaluate the efficacy and safety of teriflunomide in
reducing the frequency of relapses and progression of physical disability in
patients with relapsing multiple sclerosis (RMS). Literatures were searched in
Pubmed, Medline and Embase to screen citations from January 1990 to April 2015.
Studies of parallel group design comparing teriflunomide and placebo for RMS were
screened. After independent review of 234 citations by two authors, seven studies
were identified as meeting the inclusion criteria. The results showed
teriflunomide (7 and 14mg) could significantly reduce annualized relapse rate and
teriflunomide at the higher dose could also decrease the disability progression
(risk ratio (RR)=0.69, 95% confidence interval (CI): 0.55-0.87). And
teriflunomide significantly reduce annualized rates of relapses with sequelae
EDSS/FS, relapses leading to hospitalization, and relapses requiring IV
corticosteroids. Patients treated with teriflunomide 14mg have a lower annualized
rate of relapses with sequelae-investigator (RR=0.37, 95% CI: 0.26-0.52).
Teriflunomide 7mg has a higher incidence of diarrhea (RR=1.73, 95% CI: 1.32-2.26)
and hair thinning (RR=1.99, 95% CI: 1.4-2.81), while teriflunomide 14mg has a
higher incidence of diarrhea (RR=1.71, 95% CI: 1.34-2.18), hair thinning
(RR=2.81, 95% CI: 2.02-3.91) and nausea (RR=1.65, 95% CI: 1.03-2.31) compared
with placebo. The incidence of elevated alanine aminotransferase levels was also
higher with teriflunomide than with placebo. However, the incidence of serious
adverse events was similar across groups. In conclusion, teriflunomide
significantly reduces annualized relapse rates and disability progression with a
similar safety and tolerability profile to placebo.
PMID- 27492049
TI - Breaking Down the Barriers to Precision Cancer Nanomedicine.
AB - Nanomedicine offers unique advantages in treating human cancers. However,
physiological and pathological barriers within normal and disease tissues, which
are highly variable among individuals, often hinder its effectiveness. The body
possesses specific innate responses to nanoparticles (NPs), which when combined
with unique pathophysiological signatures in the tumor microenvironment, can
severely limit the utility of nanomedicine in the oncological setting.
Furthermore, with the successes of cancer immunotherapies, understanding
nanoimmune interactions and developing immune-smart cancer nanomedicine that can
take advantage of the body's immune functions will increasingly become clinically
relevant. Therefore, a better understanding of the important native and acquired
biological processes that dictate the fate of nanomedicine is integral to
developing more effective individualized platforms for treating cancer patients.
PMID- 27492050
TI - Interactions of rod-like particles on responsive elastic sheets.
AB - What are the physical laws of the mutual interactions of objects bound to cell
membranes, such as various membrane proteins or elongated virus particles? To
rationalise this, we here investigate by extensive computer simulations mutual
interactions of rod-like particles adsorbed on the surface of responsive elastic
two-dimensional sheets. Specifically, we quantify sheet deformations as a
response to adhesion of such filamentous particles. We demonstrate that tip-to
tip contacts of rods are favoured for relatively soft sheets, while side-by-side
contacts are preferred for stiffer elastic substrates. These attractive
orientation-dependent substrate-mediated interactions between the rod-like
particles on responsive sheets can drive their aggregation and self-assembly. The
optimal orientation of the membrane-bound rods is established via responding to
the elastic energy profiles created around the particles. We unveil the phase
diagramme of attractive-repulsive rod-rod interactions in the plane of their
separation and mutual orientation. Applications of our results to other systems
featuring membrane-associated particles are also discussed.
PMID- 27492052
TI - Endogenous Technology Adoption and Medical Costs.
AB - Despite the claim that technology has been one of the most important drivers of
healthcare spending growth over the past decades, technology variables are rarely
introduced explicitly in cost equations. Furthermore, technology is often
considered exogenous. Using 1996-2007 panel data on Swiss geographical areas, we
assessed the impact of technology availability on per capita healthcare spending
covered by basic health insurance whilst controlling for the endogeneity of
health technology availability variables. Our results suggest that medical
research, patent intensity and the density of employees working in the medical
device industry are influential factors for the adoption of technology and can be
used as instruments for technology availability variables in the cost equation.
These results are similar to previous findings: CT and PET scanner adoption is
associated with increased healthcare spending, whilst increased availability of
percutaneous transluminal coronary angioplasty facilities is associated with
reductions in per capita spending. However, our results suggest that the
magnitude of these relationships is much greater in absolute value than that
suggested by previous studies that did not control for the possible endogeneity
of the availability of technologies. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27492053
TI - Prognostic value of computed tomography in acute pulmonary thromboembolism.
AB - In addition to being the standard reference for the diagnosis of acute pulmonary
thromboembolism, CT angiography of the pulmonary arteries can also provide
valuable information about the patient's prognosis. Although which imaging
findings are useful for prognosis remains controversial, signs of right
ventricular dysfunction on CT are now included in clinical algorithms for the
management of pulmonary thromboembolism. However, the optimal method for
obtaining these measurements while maintaining a balance between the ease of use
necessary to include their evaluation in our daily activity and the loss of
precision in its predictive capacity remains to be determined. Moreover, other
variables associated with pulmonary thromboembolism that often go unobserved can
complement the prognostic information we can offer to clinicians. This review
aims to clarify some of the more controversial aspects related to the prognostic
value of CT in patients with pulmonary embolisms according to the available
evidence. Knowing which variables are becoming more important in the prognosis,
how to detect them, and why it is important to include them in our reports will
help improve the management of patients with pulmonary embolism.
PMID- 27492054
TI - Reduced CD161+ MAIT cell frequencies in HCV and HIV/HCV co-infection: Is the
liver the heart of the matter?
PMID- 27492055
TI - Joint society statement for the elimination of viral hepatitis.
PMID- 27492057
TI - Probing non-covalent interactions with a second generation energy decomposition
analysis using absolutely localized molecular orbitals.
AB - An energy decomposition analysis (EDA) separates a calculated interaction energy
into as many interpretable contributions as possible; for instance, permanent and
induced electrostatics, Pauli repulsions, dispersion and charge transfer. The
challenge is to construct satisfactory definitions of all terms in the chemically
relevant regime where fragment densities overlap, rendering unique definitions
impossible. Towards this goal, we present an improved EDA for Kohn-Sham density
functional theory (DFT) with properties that have previously not been
simultaneously attained. Building on the absolutely localized molecular orbital
(ALMO)-EDA, this second generation ALMO-EDA is variational and employs valid
antisymmetric electronic wavefunctions to produce all five contributions listed
above. These contributions moreover all have non-trivial complete basis set
limits. We apply the EDA to the water dimer, the T-shaped and parallel-displaced
benzene dimer, the p-biphthalate dimer "anti-electrostatic" hydrogen bonding
complex, the biologically relevant binding of adenine and thymine in stacked and
hydrogen-bonded configurations, the triply hydrogen-bonded guanine-cytosine
complex, the interaction of Cl(-) with s-triazine and with the 1,3-dimethyl
imidazolium cation, which is relevant to the study of ionic liquids, and the
water-formaldehyde-vinyl alcohol ter-molecular radical cationic complex formed in
the dissociative photoionization of glycerol.
PMID- 27492056
TI - Induction of DNA damage and erroneous repair can explain genomic instability
caused by endosulfan.
AB - Endosulfan (ES) is an organochlorine pesticide, speculated to be associated with
chromosomal abnormalities and diseases in humans. However, very little is known
about the mechanism of its genotoxicity. Using in vivo, ex vivo and in vitro
model systems, we show that exposure to ES induces reactive oxygen species (ROS)
in a concentration and time-dependent manner. The generation of ROS results in
DNA double-strand breaks either directly or in a replication-dependent manner,
both in mice and human cells. Importantly, ES-induced DNA damage evokes DNA
damage response, resulting in elevated levels of classical non-homologous DNA
endjoining (NHEJ), the predominant double-strand break repair pathway in higher
eukaryotes. Sequence analyses of NHEJ junctions revealed that ES treatment
results in extensive processing of broken DNA, culminating in increased and long
junctional deletions, thereby favoring erroneous repair. We also find that
exposure to ES leads to significant increase in microhomology-mediated end
joining (MMEJ), a LIGASE III-dependent alternative repair pathway. Therefore, we
demonstrate that ES induces DNA damage and genomic instability, alters DNA damage
response thereby promoting erroneous DNA repair.
PMID- 27492058
TI - Multiplex 16S rRNA-derived geno-biochip for detection of 16 bacterial pathogens
from contaminated foods.
AB - Foodborne diseases caused by various pathogenic bacteria occur worldwide. To
prevent foodborne diseases and minimize their impacts, it is important to inspect
contaminated foods and specifically detect many types of pathogenic bacteria.
Several DNA oligonucleotide biochips based on 16S rRNA have been investigated to
detect bacteria; however, a mode of detection that can be used to detect diverse
pathogenic strains and to examine the safety of food matrixes is still needed. In
the present work, a 16S rRNA gene-derived geno-biochip detection system was
developed after screening DNA oligonucleotide specific capture probes, and it was
validated for multiple detection of 16 pathogenic strains that frequently occur
with a signature pattern. rRNAs were also used as detection targets directly
obtained from cell lysates without any purification and amplification steps in
the bacterial cells separated from 8 food matrixes by simple pretreatments. Thus,
the developed 16S rRNA-derived geno-biochip can be successfully used for the
rapid and multiple detection of the 16 pathogenic bacteria frequently isolated
from contaminated foods that are important for food safety.
PMID- 27492059
TI - Plant-mediated interactions between two herbivores differentially affect a
subsequently arriving third herbivore in populations of wild cabbage.
AB - Plants are part of biodiverse communities and frequently suffer from attack by
multiple herbivorous insects. Plant responses to these herbivores are specific
for insect feeding guilds: aphids and caterpillars induce different plant
phenotypes. Moreover, plants respond differentially to single or dual herbivory,
which may cascade into a chain of interactions in terms of resistance to other
community members. Whether differential responses to single or dual herbivory
have consequences for plant resistance to yet a third herbivore is unknown. We
assessed the effects of single or dual herbivory by Brevicoryne brassicae aphids
and/or Plutella xylostella caterpillars on resistance of plants from three
natural populations of wild cabbage to feeding by caterpillars of Mamestra
brassicae. We measured plant gene expression and phytohormone concentrations to
illustrate mechanisms involved in induced responses. Performance of both B.
brassicae and P. xylostella was reduced when feeding simultaneously with the
other herbivore, compared to feeding alone. Gene expression and phytohormone
concentrations in plants exposed to dual herbivory were different from those
found in plants exposed to herbivory by either insect alone. Plants previously
induced by both P. xylostella and B. brassicae negatively affected growth of the
subsequently arriving M. brassicae. Furthermore, induced responses varied between
wild cabbage populations. Feeding by multiple herbivores differentially activates
plant defences, which has plant-mediated negative consequences for a subsequently
arriving herbivore. Plant population-specific responses suggest that plant
populations adapt to the specific communities of insect herbivores. Our study
contributes to the understanding of plant defence plasticity in response to
multiple insect attacks.
PMID- 27492062
TI - Soft-tissue defects of the Achilles tendon region: Management and reconstructive
ladder. Review of the literature.
AB - INTRODUCTION: Defects of the Achilles tendon region represent a challenge for
reconstructive surgeons. Several options are available but there is still no
reconstructive ladder for this specific and tricky area. An up-to-date
reconstructive ladder according to local and general conditions is proposed based
on our multicentre experience and an extensive review of the English literature
on PubMed. MATERIALS AND METHODS: An extensive review of the English literature
was performed on PubMed using the following key-words: "Achilles region", "heel",
"soft-tissue reconstruction", "flaps", "grafts" and "dermal substitutes".
RESULTS: A total of 69 complete papers were selected, covering the last thirty
years' literature. Although most of the studies were based on limited case
series, local and general conditions were always reported. A comprehensive
reconstructive ladder of all the available reconstructive techniques for the
Achilles region has been created based on our personal multicentre experience and
the results of the literature review. CONCLUSIONS: The reconstructive ladder is a
concept that is still a mainstay in plastic surgery and guides decisions in the
repair strategy for soft tissue defects. The optimal solution, according to the
experience of the surgeon and the wishes of the patient, is the one that implies
less sacrifice of the donor site. Perforator flaps should be the first-line
option for small-to-moderate defects; the distally-based sural flap is the most
reported for moderate-to-large defects of the Achilles region, and free flaps
should be reserved mainly for complex and wide reconstructions.
PMID- 27492061
TI - Long-range movement of large mechanically interlocked DNA nanostructures.
AB - Interlocked molecules such as catenanes and rotaxanes, connected only via
mechanical bonds have the ability to perform large-scale sliding and rotational
movements, making them attractive components for the construction of artificial
molecular machines and motors. We here demonstrate the realization of large,
rigid rotaxane structures composed of DNA origami subunits. The structures can be
easily modified to carry a molecular cargo or nanoparticles. By using multiple
axle modules, rotaxane constructs are realized with axle lengths of up to 355 nm
and a fuel/anti-fuel mechanism is employed to switch the rotaxanes between a
mobile and a fixed state. We also create extended pseudo-rotaxanes, in which
origami rings can slide along supramolecular DNA filaments over several hundreds
of nanometres. The rings can be actively moved and tracked using atomic force
microscopy.
PMID- 27492063
TI - Minimally-invasive treatment of calcaneal fractures: A review of the literature
and our experience.
AB - The optimal treatment of calcaneal fractures (CF) is currently controversial and
is still under debate. It is well established that conservative treatment of
these fractures is associated with poor results. Several surgical techniques are
described in the literature; however, there is no consensus on which of these is
more effective. The main goals of surgery are to restore the subtalar joint
congruence, and calcaneal width, height, shape and alignment, thus avoiding
medial and lateral impingement and enabling the patient to resume a normal
lifestyle. ORIF is the most popular technique for these fractures, but it is
associated with high rates of wound complications, hardware failure and
infections. Several minimally-invasive techniques have been developed recently
for the treatment of CF, with the common aim to be as simple, effective and
inexpensive as possible and to reduce surgical times, complications and length of
hospital stay.
PMID- 27492064
TI - Unblinded randomized control trial on prophylactic antibiotic use in gustilo II
open tibia fractures at Kenyatta National Hospital, Kenya.
AB - OBJECTIVE: To determine the difference in infection rate between 24h versus five
days of prophylactic antibiotic use in management of Gustilo II open tibia
fractures. DESIGN: Unblinded randomized control trial. SETTING: Accident and
Emergency, orthopedic wards and outpatient clinics at Kenyatta National Hospital
(KNH). PATIENTS: The study involved patients aged 18-80 years admitted through
accident and emergency department with Gustilo II traumatic open tibia fractures.
INTERVENTION: Patients were randomized into either 24hour or five day group and
antibiotics started for 24hours or five days after surgical debridement. The
wounds were exposed and scored using ASEPSIS wound scoring system for infection
after 48h, 5days and at 14days. OUTCOME MEASURES: The main outcomes of interest
were presence of infection at days 2, 5 and 14 and effect of duration to
antibiotic administration on infection rate. RESULTS: There was no significant
difference in infection rates between 24-hour and 5-day groups with infection
rates of 23% (9/40) vs. 19% (7/37) respectively (p=0.699). The infection rate was
significantly associated with time lapsed before administration of antibiotics
(p=0.004). CONCLUSION: In the use of prophylactic antibiotics for the management
of Gustilo II traumatic open tibia fractures, there is no difference in infection
rate between 24hours and five days regimen but time to antibiotic administration
correlates with infection rate. Antibiotic use for 24hours only has proven
adequate prophylaxis against infection. This is underlined in our study which we
hope shall inform practice in our setting. A larger, more appropriately
controlled study would be useful.
PMID- 27492066
TI - Extra-articular distal tibia facture (AO-43A): A retrospective study comparing
modified MIPPO with IMN.
AB - PURPOSE: We introduce a new MIPPO procedure which is simple and effective for the
treatment of extra-articular distal tibia facture (AO-43A). The aim of this
retrospective study was to compare our modified MIPPO with IMN. MATERIALS AND
METHODS: This retrospective study included 64 patients treated with our modified
MIPPO and 61 patients with IMN. The data of sex, age, operation time, blood loss,
wound complications, mal-reduction, shortening and fracture healing was analyzed.
RESULTS: The operation time was significantly shorter in the MIPPO group than in
the IMN group (56.0min vs. 85.0min, P<0.001). There were 5 patients (8.2%) in the
IMN group and 2 patients (3.1%) in the MIPPO group who had wound complications
(P=0.399). Mal-reduction occurred in 17 patients (27.9%) managed with IMN and in
3 patients (4.7%) who had MIPPO (P<0.001). Furthermore, no patients had a
left/right difference in the length of the tibia of >1cm and nonunion in both
groups. CONCLUSIONS: Our results have shown that our modified MIPPO has enormous
advantages over IMN for extra-articular distal tibia fracture (AO-43A).
PMID- 27492065
TI - Comparative evaluation of MicroDTTect device and flocked swabs in the diagnosis
of prosthetic and orthopaedic infections.
AB - The evolution of new prosthetic and osteosynthetic devices has led to more
surgical indications, and this is accompanied by an increased incidence of septic
complications in orthopaedic and trauma surgery in the general population. The
strategy for choosing surgical or therapeutic (conservative) treatment is based
on the identification of the pathogen: knowledge of the aetiological agents is an
essential element in the decision-making process to ensure the most effective
treatment is administered. The pathogen also needs to be considered in the
challenging case of doubtful infection, where perhaps the only sign is
inflammation, for a more accurate prediction of progression to either sepsis or
healing. Biofilm-related infections and low-grade infections may fall into this
category. Biofilm slows the metabolism of microorganisms and prolongs their
survival, which renders them resistant to antibiotics. Moreover, when
microorganisms are embedded in the biofilm they are poorly recognised by the
immune system and the infection becomes chronic. As recently demonstrated,
isolation and identification of bacteria in biofilm is difficult as the bacteria
are concealed. The development of an effective means of sample collection and
laboratory methods that can dislodge bacteria from prosthetic surfaces has
therefore become necessary. The primary aim of the study was to evaluate the
reliability of an innovative technology (MicroDTTect), specifically applied to
collect and transport explanted samples (prostheses, osteosynthetic devices,
biological tissues), and compare with flocked swabs. The MicroDTTect system is
quick and simple to use and, most importantly, is a closed system that is totally
sterile and safe for the patient being treated. It contains a specific
concentration of dithiotreitol (DTT) that can dislodge bacteria from the biofilm
adhering to prosthetic surfaces. The numbers of positive and negative samples
were measured to compare the MicroDTTect methodology with swab collection in 30
procedures. The results showed that MicroDTTect had a higher sensitivity compared
to swabs (77% and 46%, respectively), and was associated with more positive
results than swabs (35% and 20%, respectively). These preliminary results show
that MicroDTTect is superior to swab collection for bacterial identification in
orthopaedic surgery. The early identification of microorganisms that cause sepsis
may help improve treatment strategies and the efficacy of therapy, which will
lead to an increased healing rate, reduced severity of sequelae and improved
quality of life.
PMID- 27492067
TI - Automated visibility map of the internal colon surface from colonoscopy video.
AB - PURPOSE: Optical colonoscopy is a prominent procedure by which clinicians examine
the surface of the colon for cancerous polyps using a flexible colonoscope. One
of the main concerns regarding the quality of the colonoscopy is to ensure that
the whole colonic surface has been inspected for abnormalities. In this paper, we
aim at estimating areas that have not been covered thoroughly by providing a map
from the internal colon surface. METHODS: Camera parameters were estimated using
optical flow between consecutive colonoscopy frames. A cylinder model was fitted
to the colon structure using 3D pseudo stereo vision and projected into each
frame. A circumferential band from the cylinder was extracted to unroll the
internal colon surface (band image). By registering these band images, drift in
estimating camera motion could be reduced, and a visibility map of the colon
surface could be generated, revealing uncovered areas by the colonoscope. Hidden
areas behind haustral folds were ignored in this study. The method was validated
on simulated and actual colonoscopy videos. The realistic simulated videos were
generated using a colonoscopy simulator with known ground truth, and the actual
colonoscopy videos were manually assessed by a clinical expert. RESULTS: The
proposed method obtained a sensitivity and precision of 98 and 96 % for detecting
the number of uncovered areas on simulated data, whereas validation on real
videos showed a sensitivity and precision of 96 and 78 %, respectively. Error in
camera motion drift could be reduced by almost 50 % using results from band image
registration. CONCLUSION: Using a simple cylindrical model for the colon and
reducing drift by registering band images allows for the generation of visibility
maps. The current results also suggest that the provided feedback through the
visibility map could enhance clinicians' awareness of uncovered areas, which in
return could reduce the probability of missing polyps.
PMID- 27492068
TI - Electromagnetic navigation versus fluoroscopy in aortic endovascular procedures:
a phantom study.
AB - PURPOSE: To explore the possible benefits of electromagnetic (EM) navigation
versus conventional fluoroscopy during abdominal aortic endovascular procedures.
METHODS: The study was performed on a phantom representing the abdominal aorta.
Intraoperative cone beam computed tomography (CBCT) of the phantom was acquired
and merged with a preoperative multidetector CT (MDCT). The CBCT was performed
with a reference plate fixed to the phantom that, after merging the CBCT with the
MDCT, facilitated registration of the MDCT volume with the EM space. An EM field
generator was stationed near the phantom. Navigation software was used to display
EM-tracked instruments within the 3D image volume. Fluoroscopy was performed
using a C-arm system. Five operators performed a series of renal artery
cannulations using modified instruments, alternatingly using fluoroscopy or EM
navigation as the sole guidance method. Cannulation durations and associated
radiation dosages were noted along with the number of cannulations complicated by
loss of guidewire insertion. RESULTS: A total of 120 cannulations were performed.
The median cannulation durations were 41.5 and 34.5 s for the fluoroscopy- and EM
guided cannulations, respectively. No significant difference in cannulation
duration was found between the two modalities (p = 0.736). Only EM navigation
showed a significant reduction in cannulation duration in the latter half of its
cannulation series compared with the first half (p = 0.004). The median dose area
product for fluoroscopy was 0.0836 [Formula: see text]. EM-guided cannulations
required a one-time CBCT dosage of 3.0278 [Formula: see text]. Three EM-guided
and zero fluoroscopy-guided cannulations experienced loss of guidewire insertion.
CONCLUSION: Our findings indicate that EM navigation is not inferior to
fluoroscopy in terms of the ability to guide endovascular interventions. Its
utilization may be of particular interest in complex interventions where adequate
visualization or minimal use of contrast agents is critical. In vivo studies
featuring an optimized implementation of EM navigation should be conducted.
PMID- 27492069
TI - Exosome cargo reflects TGF-beta1-mediated epithelial-to-mesenchymal transition
(EMT) status in A549 human lung adenocarcinoma cells.
AB - It has been suggested that tumor cells secrete exosomes to modify the local
microenvironment, which then promotes intercellular communication and metastasis.
Although exosomes derived from cancer cells may contribute to the epithelial
mesenchymal transition (EMT) in untransformed cells, few studies have defined
exosome cargo upon induction of EMT. In this study, we investigated the changes
in exosomal cargo from the epithelial to mesenchymal cell phenotype by inducing
EMT with transforming growth factor (TGF)-beta1 in A549 human lung adenocarcinoma
cells. The protein content of the exosomes reflects the change in the cell
phenotype. In addition, miR-23a was significantly enriched in the exosomes after
mesenchymal transition. Following treatment of exosomes from mesenchymal cells
via EMT induction with TGF-beta1 to the epithelial cell type, phenotypic changes
in protein expression level and cell morphology were observed. Autologous
treatment of exosomes enhanced the transcriptional activity and abundance of beta
catenin. Our results suggest that the exosomal protein and miRNA content reflects
the physiological condition of its source and that exosomes induce phenotypic
changes via autocrine signaling.
PMID- 27492071
TI - The nature of organic records in impact excavated rocks on Mars.
AB - Impact ejected rocks are targets for life detection missions to Mars. The Martian
subsurface is more favourable to organic preservation than the surface owing to
an attenuation of radiation and physical separation from oxidising materials with
increasing depth. Impact events bring materials to the surface where they may be
accessed without complicated drilling procedures. On Earth, different assemblages
of organic matter types are derived from varying depositional environments. Here
we assess whether these different types of organic materials can survive impact
events without corruption. We subjected four terrestrial organic matter types to
elevated pressures and temperatures in piston-cylinder experiments followed by
chemical characterisation using whole-rock pyrolysis-gas chromatography-mass
spectrometry. Our data reveal that long chain hydrocarbon-dominated organic
matter (types I and II; mainly microbial or algal) are unresistant to pressure
whereas aromatic hydrocarbon-dominated organic matter types (types III and IV;
mainly land plant, metamorphosed or degraded, displaying some superficial
chemical similarities to abiotic meteoritic organic matter) are relatively
resistant. This suggests that the impact excavated record of potential biology on
Mars will be unavoidably biased, with microbial organic matter underrepresented
while metamorphosed, degraded or abiotic meteoritic organic matter types will be
selectively preserved.
PMID- 27492070
TI - Amyloid-beta and tau pathology following repetitive mild traumatic brain injury.
AB - Neurodegenerative diseases are characterized by distinctive neuropathological
alterations, including the cerebral accumulation of misfolded protein aggregates,
neuroinflammation, synaptic dysfunction, and neuronal loss, along with behavioral
impairments. Traumatic brain injury (TBI) is believed to be an important risk
factor for certain neurodegenerative diseases, such as Alzheimer's disease (AD)
and chronic traumatic encephalopathy (CTE). TBI represents a ubiquitous problem
in the world and could play a major role in the pathogenesis and etiology of AD
or CTE later in life. TBI events appear to trigger and exacerbate some of the
pathological processes in these diseases, in particular, the formation and
accumulation of misfolded protein aggregates composed of amyloid-beta (Abeta) and
tau. Here, we describe the relationship between repetitive mild TBI and the
development of Abeta and tau pathology in patients affected by AD or CTE on the
basis of epidemiological and pathological studies in human cases, and a thorough
overview of data obtained in experimental animal models. We also discuss the
possibility that TBI may contribute to initiate the formation of misfolded
oligomeric species that may subsequently spread the pathology through a prion
like process of seeding of protein misfolding.
PMID- 27492072
TI - Vascular Dysfunction in Leukoaraiosis.
AB - BACKGROUND AND PURPOSE: The pathogenesis of leukoaraiosis has long been debated.
This work addresses a less well-studied mechanism, cerebrovascular reactivity,
which could play a leading role in the pathogenesis of this disease. Our aim was
to evaluate blood flow dysregulation and its relation to leukoaraiosis. MATERIALS
AND METHODS: Cerebrovascular reactivity, the change in the blood oxygen level
dependent 3T MR imaging signal in response to a consistently applied step change
in the arterial partial pressure of carbon dioxide, was measured in white matter
hyperintensities and their contralateral spatially homologous normal-appearing
white matter in 75 older subjects (age range, 50-91 years; 40 men) with
leukoaraiosis. Additional quantitative evaluation of regions of leukoaraiosis was
performed by using diffusion (n = 75), quantitative T2 (n = 54), and DSC
perfusion MRI metrics (n = 25). RESULTS: When we compared white matter
hyperintensities with contralateral normal-appearing white matter,
cerebrovascular reactivity was lower by a mean of 61.2% +/- 22.6%, fractional
anisotropy was lower by 44.9 % +/- 6.9%, and CBF was lower by 10.9% +/- 11.9%. T2
was higher by 61.7% +/- 13.5%, mean diffusivity was higher by 59.0% +/- 11.7%,
time-to-maximum was higher by 44.4% +/- 30.4%, and TTP was higher by 6.8% +/-
5.8% (all P < .01). Cerebral blood volume was lower in white matter
hyperintensities compared with contralateral normal-appearing white matter by
10.2% +/- 15.0% (P = .03). CONCLUSIONS: Not only were resting blood flow metrics
abnormal in leukoaraiosis but there is also evidence of reduced cerebrovascular
reactivity in these areas. Studies have shown that reduced cerebrovascular
reactivity is more sensitive than resting blood flow parameters for assessing
vascular insufficiency. Future work is needed to examine the sensitivity of
resting-versus-dynamic blood flow measures for investigating the pathogenesis of
leukoaraiosis.
PMID- 27492074
TI - Neuroimaging Findings in Congenital Zika Syndrome.
PMID- 27492075
TI - Reply.
PMID- 27492073
TI - Progressing Bevacizumab-Induced Diffusion Restriction Is Associated with
Coagulative Necrosis Surrounded by Viable Tumor and Decreased Overall Survival in
Patients with Recurrent Glioblastoma.
AB - BACKGROUND AND PURPOSE: Patients with recurrent glioblastoma often exhibit
regions of diffusion restriction following the initiation of bevacizumab therapy.
Studies suggest that these regions represent either diffusion-restricted necrosis
or hypercellular tumor. This study explored postmortem brain specimens and a
population analysis of overall survival to determine the identity and
implications of such lesions. MATERIALS AND METHODS: Postmortem examinations were
performed on 6 patients with recurrent glioblastoma on bevacizumab with
progressively growing regions of diffusion restriction. ADC values were extracted
from regions of both hypercellular tumor and necrosis. A receiver operating
characteristic analysis was performed to define optimal ADC thresholds for
differentiating tissue types. A retrospective population study was also performed
comparing the overall survival of 64 patients with recurrent glioblastoma treated
with bevacizumab. Patients were separated into 3 groups: no diffusion
restriction, diffusion restriction that appeared and progressed within 5 months
of bevacizumab initiation, and delayed or stable diffusion restriction. An
additional analysis was performed assessing tumor O6-methylguanine-DNA
methyltransferase methylation. RESULTS: The optimal ADC threshold for
differentiation of hypercellularity and necrosis was 0.736 * 10-3mm2/s.
Progressively expanding diffusion restriction was pathologically confirmed to be
coagulative necrosis surrounded by viable tumor. Progressive lesions were
associated with the worst overall survival, while stable lesions showed the
greatest overall survival (P < .05). Of the 40% of patients with O6-methylguanine
DNA-methyltransferase methylated tumors, none developed diffusion-restricted
lesions. CONCLUSIONS: Progressive diffusion-restricted lesions were
pathologically confirmed to be coagulative necrosis surrounded by viable tumor
and associated with decreased overall survival. Stable lesions were, however,
associated with increased overall survival. All lesions were associated with O6
methylguanine-DNA-methyltransferase unmethylated tumors.
PMID- 27492076
TI - Comment on "SAPHO Syndrome: Imaging Findings of Vertebral Involvement".
PMID- 27492077
TI - Insight into the Epigenetics of Alzheimer's Disease: A Computational Study from
Human Interactome.
AB - BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative
disease throughout the world. Most of the clinical symptoms of AD appear at a
very later stage, therefore, the identification of disease markers is essential
which can help proper detection of AD at an earlier stage and slow down its
progression. Studies have implicated that epigenetic biomarkers, such as DNA
methylation, histone modification and non coding RNA mediated regulation serve
crucial roles in several disease progression including AD. OBJECTIVE: The aim of
our study was to identify the topologically significant AD-related proteins from
experimentally validated human protein-protein interaction database, HPRD
(interactome) and find out novel epigenetic biomarkers. METHOD: In this
computational work, we constructed AD specific diseasome from AD genelist and
interactome. Using this diseasome we screened the interactome with the help of
novel parameters namely degree band and similarity index and identified AD
related proteins. Regulatory network involving AD related proteins, not
previously known to be associated with AD was constructed. Several network motifs
and epigenetic modification patterns of regulators of these motifs were studied.
RESULT: Our study identified computationally predicted 22 epigenetic genes and 11
epigenetic miRs, not previously known to be associated with AD, from the network
motifs. Most of these genes and miRs show brain specific expression. Further
study on the epigenetic modification patterns of these regulators regarding
histone modification, CpG island and lncRNAs strengthened their association in
AD. CONCLUSION: Computationally predicted genes and miRs identified in our study
might provide insight into new epigenetic AD therapeutic targets.
PMID- 27492078
TI - Environmental Variables That Influence Patient Satisfaction: A Review of the
Literature.
AB - Patient's perception of care-referred to as patient satisfaction-is of great
interest in the healthcare industry, as it becomes more directly tied to the
revenue of the health system providers. The perception of care has now become
important in addition to the actual health outcome of the patient. The known
influencers for the patient perception of care are the patient's own
characteristics as well as the quality of service received. In patient surveys,
the physical environment is noted as important for being clean and quiet but is
not considered a critical part of patient satisfaction or other health outcomes.
Patient perception of care is currently measured as patient satisfaction, a
systematic collection of perceptions of social interactions from an individual
person as well as their interaction with the environment. This exploration of the
literature intends to explore the rigorous, statistically tested research
conducted that has a spatial predictor variable and a health or behavior outcome,
with the intent to begin to further test the relationships of these variables in
the future studies. This literature review uses the patient satisfaction
framework of components of influence and identifies at least 10 known spatial
environmental variables that have been shown to have a direct connection to the
health and behavior outcome of a patient. The results show that there are certain
features of the spatial layout and environmental design in hospital or work
settings that influence outcomes and should be noted in the future research.
PMID- 27492080
TI - Transcription factor ZFP38 is essential for meiosis prophase I in male mice.
AB - The production of haploid gametes by meiosis is a cornerstone of sexual
reproduction and maintenance of genome integrity. Zfp38 mRNA is expressed in
spermatocytes, indicating that transcription factor ZFP38 has the potential to
regulate transcription during meiosis. In this study, we generated Zfp38
conditional knockout mice (Zfp38(flox/flox), Stra8-Cre, hereafter called Zfp38
cKO) and found that spermatogenesis did not progress beyond meiosis prophase I in
Zfp38 cKO mice. Using a chromosomal spread technique, we observed that Zfp38 cKO
spermatocytes exhibited a failure in chromosomal synapsis observed by SYCP1/SYCP3
double staining. Progression of DNA double-strand breaks (DSB) repair is
disrupted in Zfp38 cKO spermatocytes, as revealed by gamma-H2AX, RAD51 and MLH1
staining. Furthermore, the mRNA and protein levels of DSB repair enzymes and
factors that guide their loading onto sites of DSBs, such as RAD51, DMC1, RAD51,
TEX15 and PALB2, were significantly reduced in Zfp38 cKO spermatocytes. Taken
together, our data suggest that ZFP38 is critical for the chromosomal synapsis
and DSB repairs partially via its regulation of DSB repair-associated protein
expression during meiotic progression in mouse.
PMID- 27492079
TI - Ovarian tissue transport to expand access to fertility preservation: from animals
to clinical practice.
AB - Primordial follicles dictate a female's reproductive life span and therefore are
central to fertility preservation for both endangered species and individuals
with fertility-threatening conditions. Ovarian tissue containing primordial
follicles can be cryopreserved and later thawed and transplanted back into
individuals to restore both endocrine function and fertility. Importantly,
increasing numbers of human live births have been reported following ovarian
tissue cryopreservation and transplantation. A current limitation of this
technology is patient access to sites that are approved or equipped to process
and cryopreserve ovarian tissue - especially in larger countries or low resource
settings. Here, we review empirical evidence from both animal models and human
studies that suggest that ovarian tissue can be transported at cold temperatures
for several hours while still maintaining the integrity and reproductive
potential of the primordial follicles within the tissue. In fact, several human
live births have been reported in European countries using tissue that was
transported at cold temperatures for up to 20 h before cryopreservation and
transplantation. Ovarian tissue transport, if implemented widely in clinical
practice, could therefore expand both patient and provider access to emerging
fertility preservation options.
PMID- 27492081
TI - Effect of kit ligand on natriuretic peptide precursor C and oocyte maturation in
cattle.
AB - In vitro maturation (IVM) of oocytes in cattle is inefficient, and there is great
interest in the development of approaches to improve maturation and fertilization
rates. Intraovarian signalling molecules are being explored as potential
additives to IVM media. One such factor is kit ligand (KITL), which stimulates
the growth of oocytes. We determined if KITL enhances oocyte maturation in
cattle. The two main isoforms of KITL (KITL1 and KITL2) were expressed in bovine
cumulus-oocyte complexes (COC), and levels of mRNA increased during FSH
stimulated IVM. The addition of KITL to the culture medium increased the
percentage of oocytes that reached meiosis II but did not affect cumulus
expansion after 22 h of IVM. Addition of KITL reduced the levels of mRNA encoding
natriuretic peptide precursor C (NPPC), a protein that holds oocytes in meiotic
arrest, and increased the levels of mRNA encoding YBX2, an oocyte-specific factor
involved in meiosis. Removal of the oocyte from the COC resulted in increased
KITL mRNA levels and decreased NPPC mRNA levels in cumulus cells, and addition of
denuded oocytes reversed these effects. Taken together, our results suggest that
KITL enhances bovine oocyte nuclear maturation through a mechanism that involves
NPPC, and that the oocyte regulates cumulus expression of KITL mRNA.
PMID- 27492083
TI - Chemoinformatic Classification Methods and their Applicability Domain.
AB - Classification rules are often used in chemoinformatics to predict categorical
properties of drug candidates related to bioactivity from explanatory variables,
which encode the respective molecular structures (i.e. molecular descriptors). To
avoid predictions with an unduly large error probability, the domain the
classifier is applied to should be restricted to the domain covered by the
training set objects. This latter domain is commonly referred to as applicability
domain in chemoinformatics. Conceptually, the applicability domain defines the
region in space where the "normal" objects are located. Defining the border of
the applicability domain may then be viewed as detecting anomalous or novel
objects or as detecting outliers. Currently two different types of measures are
in use. The first one defines the applicability domain solely in terms of the
molecular descriptor space, which is referred to as novelty detection. The second
type defines the applicability domain in terms of the expected reliability of the
predictions which is referred to as confidence estimation. Both types are
systematically differentiated here and the most popular measures are reviewed. It
will be shown that all common chemoinformatic classifiers have built-in
confidence scores. Since confidence estimation uses information of the class
labels for computing the confidence scores, it is expected to be more efficient
in reducing the error rate than novelty detection, which solely uses the
information of the explanatory variables.
PMID- 27492084
TI - Advances in Activity Cliff Research.
AB - Activity cliffs, i.e. similar compounds with large potency differences, are of
interest from a chemical and informatics viewpoint; as a source of structure
activity relationship information, for compound optimization, and activity
prediction. Herein, recent highlights of activity cliff research are discussed
including studies that have further extended our understanding of activity
cliffs, yielded unprecedented insights, or paved the way for practical
applications.
PMID- 27492082
TI - The roles of non-coding RNAs in Parkinson's disease.
AB - Parkinson's disease (PD) is considered as a high prevalence neurodegenerative
disorders worldwide. Pathologically, the demise of dopamine-producing cells, in
large part due to an abnormal accumulation of the alpha-synuclein in the
substantia nigra, is one of the main causes of the disease. Up until now, many de
novo investigations have been conducted to disclose the mechanisms underlying in
PD. Among them, impacts of non-coding RNAs (ncRNAs) on the pathogenesis and/or
progression of PD need to be highlighted. microRNAs (miRNAs) and long ncRNAs
(lncRNAs) are more noteworthy in this context. miRNAs are small ncRNAs (with 18
25 nucleotide in length) that control the expression of multiple genes at post
transcriptional level, while lncRNAs have longer size (over 200 nucleotides) and
are involved in some key biological processes through various mechanisms.
Involvement of miRNAs has been well documented in the development of PD,
particularly gene expression. Hence, in this current review, we will discuss the
impacts of miRNAs in regulation of the expression of PD-related genes and the
role of lncRNAs in the pathogenesis of PD.
PMID- 27492085
TI - Designing Multi-target Compound Libraries with Gaussian Process Models.
AB - We present the application of machine learning models to selecting G protein
coupled receptor (GPCR)-focused compound libraries. The library design process
was realized by ant colony optimization. A proprietary Boehringer-Ingelheim
reference set consisting of 3519 compounds tested in dose-response assays at 11
GPCR targets served as training data for machine learning and activity
prediction. We compared the usability of the proprietary data with a public data
set from ChEMBL. Gaussian process models were trained to prioritize compounds
from a virtual combinatorial library. We obtained meaningful models for three of
the targets (5-HT2c , MCH, A1), which were experimentally confirmed for 12 of 15
selected and synthesized or purchased compounds. Overall, the models trained on
the public data predicted the observed assay results more accurately. The results
of this study motivate the use of Gaussian process regression on public data for
virtual screening and target-focused compound library design.
PMID- 27492086
TI - Development of Quantum Chemical Method to Calculate Half Maximal Inhibitory
Concentration (IC50 ).
AB - Till date theoretical calculation of the half maximal inhibitory concentration
(IC50 ) of a compound is based on different Quantitative Structure Activity
Relationship (QSAR) models which are empirical methods. By using the Cheng
Prusoff equation it may be possible to compute IC50 , but this will be
computationally very expensive as it requires explicit calculation of binding
free energy of an inhibitor with respective protein or enzyme. In this article,
for the first time we report an ab initio method to compute IC50 of a compound
based only on the inhibitor itself where the effect of the protein is reflected
through a proportionality constant. By using basic enzyme inhibition kinetics and
thermodynamic relations, we derive an expression of IC50 in terms of
hydrophobicity, electric dipole moment (MU) and reactivity descriptor (omega) of
an inhibitor. We implement this theory to compute IC50 of 15 HIV-1 capsid
inhibitors and compared them with experimental results and available other QASR
based empirical results. Calculated values using our method are in very good
agreement with the experimental values compared to the values calculated using
other methods.
PMID- 27492087
TI - Hydration Free Energy as a Molecular Descriptor in Drug Design: A Feasibility
Study.
AB - In this work the idea was investigated whether calculated hydration energy
(DeltaGhyd ) can be used as a molecular descriptor in defining promising regions
of chemical space for drug design. Calculating DeltaGhyd using the Density
Solvation Model (SMD) in conjunction with the density functional theory (DFT)
gave an excellent correlation with experimental values. Furthermore, calculated
DeltaGhyd correlates reasonably well with experimental water solubility (r(2)
=0.545) and also log P (r(2) =0.530). Three compound collections were used: Known
drugs (n=150), drug-like compounds (n=100) and simple organic compounds (n=140).
As an approximation only molecules, which do not de/protonate at physiological pH
were considered. A relatively broad distribution was seen for the known drugs
with an average at -15.3 kcal/mol and a standard deviation of 7.5 kcal/mol.
Interestingly, much lower averages were found for the drug-like compounds (-7.5
kcal/mol) and the simple organic compounds (-3.1 kcal/mol) with tighter
distributions; 4.3 and 3.2 kcal/mol, respectively. This trend was not observed
for these collections when calculated log P and log S values were used. The
considerable greater exothermic DeltaGhyd average for the known drugs clearly
indicates in order to develop a successful drug candidate value of DeltaGhyd <-5
kcal/mol or less is preferable.
PMID- 27492089
TI - Early identification of sepsis in hospital inpatients by ward nurses increases 30
day survival.
AB - BACKGROUND: Systemic inflammatory response syndrome (SIRS) and sepsis are now
frequently identified by observations of vital signs and detection of organ
failure during triage in the emergency room. However, there is less focus on the
effect on patient outcome with better observation and treatment at the ward
level. METHODS: This was a before-and-after intervention study in one emergency
and community hospital within the Mid-Norway Sepsis Study catchment area. All
patients with confirmed bloodstream infection have been prospectively registered
continuously since 1994. Severity of sepsis, observation frequency of vital
signs, treatment data, length of stay (LOS) in high dependency and intensive care
units, and mortality were retrospectively registered from the patients' medical
journals. RESULTS: The post-intervention group (n = 409) were observed better and
had higher odds of surviving 30 days (OR 2.7, 95 % CI 1.6, 4.6), lower
probability of developing severe organ failure (0.7, 95 % CI 0.4, 0.9), and on
average, 3.7 days (95 % CI 1.5, 5.9 days) shorter LOS than the pre-intervention
group (n = 472). CONCLUSIONS: In a cohort with stable mortality rates, early
sepsis recognition by ward nurses may have reduced progression of disease and
improved survival for patients in hospital with sepsis.
PMID- 27492090
TI - Corneal inlays for spectacle independence: Friend or foe?
PMID- 27492088
TI - Coiled-coils: The long and short of it.
AB - Coiled-coils are found in proteins throughout all three kingdoms of life. Coiled
coil domains of some proteins are almost invariant in sequence and length,
betraying a structural and functional role for amino acids along the entire
length of the coiled-coil. Other coiled-coils are divergent in sequence, but
conserved in length, thereby functioning as molecular spacers. In this capacity,
coiled-coil proteins influence the architecture of organelles such as centrioles
and the Golgi, as well as permit the tethering of transport vesicles. Specialized
coiled-coils, such as those found in motor proteins, are capable of propagating
conformational changes along their length that regulate cargo binding and motor
processivity. Coiled-coil domains have also been identified in enzymes, where
they function as molecular rulers, positioning catalytic activities at fixed
distances. Finally, while coiled-coils have been extensively discussed for their
potential to nucleate and scaffold large macromolecular complexes, structural
evidence to substantiate this claim is relatively scarce.
PMID- 27492091
TI - Scleral fixation of a foldable intraocular lens with polytetrafluoroethylene
sutures through a Hoffman pocket.
AB - Scleral fixation of intraocular lenses (IOLs) is traditionally performed after
conjunctival dissection and preparation of scleral flaps. The Hoffman pocket
technique creates scleral pockets without conjunctival dissection. We describe a
technique that uses a Hoffman pocket and 7-0 polytetrafluoroethylene (Gore-Tex)
sutures for scleral fixation of a foldable posterior chamber IOL in patients with
insufficient capsule support. The technique eliminates the need for conjunctival
dissection, scleral cauterization, knot rotation, and sutured wound closure. The
favorable properties of the suture material and the use of a small incision to
insert a foldable IOL are additional advantages. FINANCIAL DISCLOSURE: None of
the authors has a financial or proprietary interest in any material or method
mentioned.
PMID- 27492092
TI - Iris fixation of unstable anterior chamber intraocular lenses.
AB - Cataract surgeons are sometimes challenged with a patient who has an unstable
anterior chamber intraocular lens (AC IOL). Over time, an unstable AC IOL can
lead to significant complications. This problem is most often addressed with an
IOL exchange using an appropriately sized AC IOL or a posterior chamber IOL with
iris or scleral fixation. We present a technique of 2-point iris fixation of
unstable AC IOLs as a simpler and less traumatic alternative. FINANCIAL
DISCLOSURE: Neither author has a financial or proprietary interest in any
material or method mentioned.
PMID- 27492093
TI - Through-focus performance with a corneal shape-changing inlay: One-year results.
AB - PURPOSE: To evaluate improvement in the through-focus acuity and visual function
provided by a corneal inlay designed to modify the surface shape of the central
cornea. SETTING: Two clinical practices, United States. DESIGN: Prospective
nonrandomized clinical trial. METHODS: Emmetropic patients with presbyopia who
required a reading addition (add) from +1.50 to +2.00 diopters (D) had
implantation of the Raindrop Near Vision Inlay in the nondominant eye. The inlay
was designed to modify the anterior curvature of the central cornea with the
intent to improve near and intermediate vision. At the preoperative and 1-year
postoperative visits, the following visual functions were recorded: defocus
curves in the nondominant eye, required add for best near vision, distance
corrected binocular contrast sensitivity, and uncorrected and corrected visual
acuity at 6 m, 80 cm, and 40 cm. RESULTS: The study comprised 30 patients. One
year postoperatively, on average, distance-corrected near acuity improved by more
than 3 lines, with patients achieving a distance-corrected acuity of 0.3 logMAR
(20/40) or better across a 3.50 D range of defocus. Binocular uncorrected visual
acuity of 0.2 logMAR (20/32) or better at distance, intermediate, and near
distances was obtained in 97% of patients. The mean reduction in the reading add
was 1.60 D. There was no significant change in binocular contrast sensitivity.
Overall patient satisfaction was high. CONCLUSION: A corneal inlay in the
nondominant eye of emmetropic patients provided a significant increase in the
range of functional vision at intermediate and near, with no loss in binocular
distance acuity. FINANCIAL DISCLOSURE: Drs. Whitman, Hovanesian, Steinert, and
Koch received compensation for participating in the study from Revision Optics,
Inc. Drs. Steinert and Koch are medical monitors for Revision Optics, Inc. None
of the other authors has a financial or proprietary interest in any material or
method mentioned.
PMID- 27492094
TI - American Society of Anesthesiologists classification in cataract surgery: Results
from the Ophthalmic Surgery Outcomes Data Project.
AB - PURPOSE: To explore the association of American Society of Anesthesiologists
(ASA) classification with cataract surgery outcomes. SETTING: Five Veterans
Affairs Medical Centers, United States. DESIGN: Retrospective observational
cohort study. METHODS: The study analyzed the outcomes of cataract surgery cases.
Corrected distance visual acuity (CDVA), unanticipated events, and vision-related
quality of life (VRQL) were assessed using the National Eye Institute Visual
Function Questionnaire (NEI-VFQ), comparing ASA classes I through IV. For some
analyses, ASA classes I and II were designated as Group A and ASA classes III and
IV were designated Group B. RESULTS: Of the 4923 cases, 875 (17.8%) were in Group
A, 4032 (81.9%) were in Group B, and 16 (0.3%) had missing data. The mean CDVA
and mean composite NEI-VFQ score improved after cataract surgery in both groups
(P < .0001); however, Group A had a better mean postoperative CDVA and
postoperative VFQ composite scores than Group B (P < .0001, both outcomes). A
higher ASA class was associated with an increased risk for 2 unanticipated
events; that is, clinically significant macular edema (CSME) (Group A: 4 [0.47%]
versus Group B: 50 [1.28%]; adjusted odds ratio [OR], 3.02; 95% confidence
interval [CI], 1.02-13.05; P = 0.04) and readmission to the hospital within 30
days (2 [0.23%] versus 56 [1.41%]; OR, 8.26; 95% CI, 1.71-148.62; P = .004)
CONCLUSIONS: Among United States veterans, the ASA classification could be an
important predictor of VRQL and visual outcomes. In this cohort, it was
associated with an increased risk for 2 serious unanticipated events-CSME and
readmission to the hospital-both costly, unwanted outcomes. FINANCIAL DISCLOSURE:
Dr. Vollman is a consultant to Forsight Vision5. None of the authors has a
financial or proprietary interest in any material or method mentioned.
PMID- 27492095
TI - Ocular-surface temperature modification by cataract surgery.
AB - PURPOSE: To analyze ocular-surface temperature changes after microincision
cataract surgery and to correlate them with surgical, clinical, and laboratory
parameters. SETTING: Ophthalmology Unit, Saint Orsola-Malpighi Hospital, Bologna,
Italy. DESIGN: Prospective case series. METHODS: Patients affected by monolateral
senile cataract were examined preoperatively and 7 days and 28 days
postoperatively. Infrared thermography was used to measure the temperature soon
after eye opening, the temperature after 10 seconds of sustained eye opening, and
the difference between these 2 values in the central cornea, nasal limbus, and
temporal limbus. The Ocular Surface Disease Index (OSDI), Schirmer test, vital
staining, tear breakup time (TBUT), conjunctival scraping cytology, exudated tear
serum albumin, and laser flare-cell meter examinations were performed. RESULTS:
The study comprised 26 patients (10 men, 16 women). The temperature changed
significantly after surgery. The temperature soon after eye opening showed
cooling in the central cornea and nasal limbus and heating in the temporal
limbus. The temperature after 10 seconds of sustained eye opening minus the
temperature soon after eye opening increased in all regions. The temperature
after 10 seconds of sustained eye opening minus the temperature soon after eye
opening in the central cornea was inversely related to the OSDI and directly
related to TBUT. The temperature soon after eye opening increased in the temporal
limbus and was directly related to inflammatory indices. CONCLUSIONS: The ocular
surface temperature changed after cataract surgery depending on the region
analyzed. The cooling in the central cornea could be related to the increased
tear-film instability. The heating in the temporal limbus could be related to
postoperative inflammation. FINANCIAL DISCLOSURE: None of the authors has a
financial or proprietary interest in any material or method mentioned.
PMID- 27492096
TI - Influence of ophthalmic viscosurgical devices on intraoperative aberrometry.
AB - PURPOSE: To determine whether the presence of an ophthalmic viscosurgical device
(OVD) in the anterior chamber influences intraoperative aberrometry and the
suggested intraocular lens (IOL) power. SETTING: Advanced Vision Care, Los
Angeles, and Specialty Surgery Center, Beverly Hills, California, USA. DESIGN:
Prospective interventional case series. METHOD: Eyes scheduled for routine
phacoemulsification and were divided into 6 equal groups, with each having 1 of 6
OVDs. After cataract removal, carefully controlled aberrometry was performed with
the anterior chamber filled with balanced salt solution (BSS). Immediately
thereafter, the BSS was replaced by 1 of the OVDs and the aberrometry repeated.
The IOL power was selected from the BSS reading, and clinical manifest refraction
was performed 3 weeks after surgery. The mean absolute error (MAE) was determined
and compared with the extrapolated refraction had the IOL power been selected
from the aberrometry reading under OVD. RESULTS: The study comprised 120 eyes, 20
in each group. The IOL power determination was lower with OVD filling the
chamber. For Discovisc and Amvisc Plus, the MAE determinations were statistically
different because the suggested IOL power was approximately 0.50 diopter less
than with a BSS fill. For the remaining OVDs (Amvisc, Healon, Healon GV, and
Provisc), the MAE differences were insignificant. The strong correlation between
differences in the index of refraction between BSS and specific OVDs appeared to
be causal. CONCLUSION: Surgeons should be aware of the influence of OVDs on the
accuracy of intraoperative aberrometry because specific agents can alter the
optical results and suggested IOL power. FINANCIAL DISCLOSURE: Dr. Masket is a
consultant to Wavetec Vision Systems, Inc., and Alcon Laboratories, Inc., and has
a research grant from Alcon Laboratories, Inc. Dr. Fram has a research grant from
Wavetec Vision Systems, Inc. Dr. Holladay is a consultant to Wavetec Vision
Systems, Inc.
PMID- 27492097
TI - Femtosecond laser penetrating corneal relaxing incisions combined with cataract
surgery.
AB - PURPOSE: To evaluate the effectiveness of femtosecond laser penetrating corneal
relaxing incisions (CRIs) in reducing corneal astigmatism during cataract
surgery. SETTING: Shanxi Eye Hospital, Taiyuan, Shanxi Province, China. DESIGN:
Prospective case series. METHODS: Using the Lensx laser, CRIs were placed at a
diameter of 8.0 mm with a depth of 90%. Corneal astigmatism was measured before
surgery and 1 and 3 months after surgery. Vector analyses were performed. To
obtain the net corneal changes, the with-the-wound (WTR) and against-the-wound
(ATR) changes were calculated along the meridian of the CRI. Multiple regression
analysis with generalized estimating equations was used to evaluate the factors
contributing to the effectiveness of CRIs. RESULTS: The study comprised 51 eyes.
One and 3 months postoperatively, respectively, the mean keratometric astigmatism
was reduced significantly by 0.65 diopter (D) and 0.67 D (both P < .05); compared
with preoperative corneal astigmatism, the percentage of eyes within +/-0.50 D of
refractive astigmatism significantly increased by 42.6% and 46.7% (both P < .05)
and the mean refractive astigmatism was significantly decreased at 1 month (0.27
@ 93 versus 0.17 * 17) (P < .05) but not at 3 months (0.09 @ 138 versus 0.07 *
172) (P > .05). The mean WTW and ATW changes were -1.05 D and -1.00 D,
respectively, and 14.9% and 6.7% of eyes, respectively, were overcorrected. Age,
CRI length, and CRI location were factors contributing to net corneal changes. A
nomogram is proposed. CONCLUSION: Femtosecond laser CRIs were effective in
reducing corneal astigmatism during cataract surgery, and their long-term
effectiveness should be evaluated. FINANCIAL DISCLOSURE: Dr. Koch is a consultant
to Abbott Medical Optics, Inc., Alcon Laboratories, Inc., and Revision Optics,
Inc. None of the other authors has a financial or proprietary interest in any
material or method mentioned.
PMID- 27492098
TI - Comparison of vitreous loss rates between manual phacoemulsification and
femtosecond laser-assisted cataract surgery.
AB - PURPOSE: To compare the vitreous loss complication rate of manual
phacoemulsification cataract surgery with that of femtosecond laser-assisted
cataract surgery. SETTING: Mercy Eye Specialists, Springfield, Missouri, USA.
DESIGN: Retrospective single-center case series. METHODS: Cataract surgeries from
2010 to 2014 performed by 4 surgeons were audited for rates of vitreous loss.
Vitreous loss data were statistically analyzed with and without exclusions.
RESULTS: Of the total 7155 cases from 2010 to 2014, 3784 were consecutively
performed using manual phacoemulsification from 2010 to 2012 and 3371 were
performed using femtosecond laser-assisted cataract surgery from 2013 to 2014.
The rate of vitreous loss with exclusions was 1.17% in the manual
phacoemulsification group and versus 0.65% femtosecond laser-assisted group;
without exclusions, the rate was 1.40% versus 0.77%. In absolute terms, the rate
decreased for every surgeon in the study. The chi-square test showed a
statistically significant association between the date of surgery, and thus
technique, and vitrectomy cases (P < .05). Odds ratio analysis with exclusions
versus without exclusions indicated that surgeries performed from 2010 to 2012
using manual phacoemulsification were 1.6 times and 1.8 times, respectively, more
likely to have vitreous loss than surgeries performed from 2013 to 2014 using the
femtosecond laser-assisted cataract surgery technique. CONCLUSIONS: Conversion
from manual phacoemulsification to femtosecond laser-assisted cataract surgery
resulted in a statistically significant decrease in vitreous loss. Because
vitreous loss increases the risk for other serious complications of cataract
surgery, this new finding has important implications for the safety of cataract
surgery. FINANCIAL DISCLOSURE: Proprietary or commercial disclosures are listed
after the references.
PMID- 27492099
TI - Accuracy of user-adjusted axial length measurements with optical biometry in eyes
having combined phacovitrectomy for macular-off rhegmatogenous retinal
detachment.
AB - PURPOSE: To evaluate the accuracy of user-adjusted axial length (AL) measured by
optical biometry for intraocular lens (IOL) calculations in eyes having combined
phacovitrectomy for macula-off rhegmatogenous retinal detachment (RRD). SETTING:
Ophthalmology Department, Calderdale Royal Hospital, Halifax, United Kingdom.
DESIGN: Retrospective case series. METHODS: Consecutive eyes having
phacovitrectomy for macula-off RRD were evaluated. The ALs were measured using
optical biometry with user adjustment to identify a posterior peak corresponding
to the eye's AL and ultrasound (US). These were compared with each other and with
the postoperative optical biometry and analyzed for accuracy as an indication of
the eye's AL. RESULTS: The study comprised 22 eyes of 22 patients. There was no
statistically significant difference between the mean AL measurements derived
from user-adjusted optical biometry and US AL (P = .964). The user-adjusted
optical biometry was not statistically significantly different from the
postoperative optical biometry (P = .242). Compared with the postoperative
optical biometry, the IOL power was within +/-0.5 diopter in 12 (92%) of 13 cases
(95% confidence interval [CI], 77.8 to 100.0) for user-adjusted optical biometry
and in 10 (77%) of 13 cases (95% CI, 54.0 to 99.8) for US measurements.
CONCLUSIONS: User-adjusted optical biometry could be used as an alternative
method for measuring AL in macula-off RRD with combined phacovitrectomy. However,
optical biometry would require assessment of agreement with US AL in cases in
which a posterior peak is not easily identifiable. User-adjusted optical biometry
might outperform US AL when calculating IOL power; however, a larger study should
be performed to confirm this. FINANCIAL DISCLOSURE: None of the authors has a
financial or proprietary interest in any material or method mentioned.
PMID- 27492100
TI - Comparative analysis of brilliant blue G and an intracameral illuminator in
assisting visualization of the anterior capsule in eyes with vitreous hemorrhage.
AB - PURPOSE: To compare the safety and efficacy of 0.025 mg/mL brilliant blue G (BBG)
and an intracameral illuminator for visualizing the anterior capsule. SETTING:
University-based tertiary referral center, South Korea. DESIGN: Retrospective
cases series. METHODS: The medical records of patients with vitreous hemorrhage
for which they had pars plana vitrectomy and cataract surgery were
retrospectively reviewed. The patients were classified into 2 groups. The BBG
group comprised patients having capsule staining with BBG. The illuminator group
comprised patients who had capsulorhexis assisted with an intracameral
illuminator. The status of the endothelial cells was analyzed. RESULTS: There
were 27 eyes in the BBG group and 35 eyes in the illuminator group. In the BBG
group, endothelial cell density (ECD) was reduced 3 months after surgery (10.6%
loss) (P = .003). The illuminator group had no significant loss (1.5% loss) (P =
.264). The ECD loss was greater in the BBG group than the illuminator group 3
months after surgery (P = .01). There was no statistically significant difference
in the coefficient of variation of cell area or percentage of hexagonal cells
between the 2 groups. CONCLUSIONS: The ECD loss was higher in eyes with 0.025
mg/mL BBG staining than in eyes using an intracameral illuminator. Further
studies are necessary to establish the safety profile of BBG on the endothelium.
FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest
in any material or method mentioned.
PMID- 27492101
TI - Optical quality and visual performance after cataract surgery with biaxial
microincision intraocular lens implantation.
AB - PURPOSE: To evaluate the time course of the optical quality and visual
performance with a microincision monofocal intraocular lens (Incise). SETTING:
Hospital Torrecardenas, Almeria, Spain. DESIGN: Prospective study. METHODS: The
visual and refractive outcomes were evaluated in eyes with the microincision IOL
preoperatively and 1, 3, and 6 months postoperatively. The modulation transfer
function (MTF) cutoff frequency, Strehl ratio, and objective scatter index (OSI)
were used to measure optical quality. The contrast sensitivity function (CSF) and
the visual disturbance index characterized visual performance. RESULTS: In the 32
study eyes, the mean values preoperatively and 6 months postoperatively,
respectively, were MTF cutoff frequency (11.40 cycles per degree [cpd] +/- 8.39
[SD] and 23.33 +/- 11.68 cpd; P < .001), Strehl ratio (0.078 +/- 0.32 and 0.15 +/
0.07; P < .05), and OSI (7.44 +/- 3.25 and 1.57 +/- 0.26; P < .001). At each
spatial frequency, the CSF significantly differed between preoperatively and
postoperatively (P < .001). The mean visual disturbance index changed from 0.70
+/- 0.28 to 0.31 +/- 0.17 (P < .001). For all parameters studied, statistically
significant differences were found between the preoperative and postoperatively
values, with no differences between the results 1, 3, and 6 months after surgery
(P > .05). CONCLUSIONS: Biaxial microincision cataract surgery provided optimum
clinical outcomes. The optical quality and visual performance improved
significantly 1 month after surgery, with the results remaining stable at 6
months. The postoperative visual function was similar to that in subjects of the
same age with healthy eyes. FINANCIAL DISCLOSURE: None of the authors has a
financial or proprietary interest in any material or method mentioned.
PMID- 27492102
TI - Using continuous intraoperative optical coherence tomography to classify swirling
lens fragments during cataract surgery and to predict their impact on corneal
endothelial cell damage.
AB - PURPOSE: To quantify and classify swirling lens fragments during cataract surgery
and record their impact on the corneal endothelium using continuous
intraoperative optical coherence tomography (OCT). SETTING: Vienna Institute for
Ocular Surgery, Hanusch Hospital, Vienna, Austria. DESIGN: Prospective case
series. METHODS: Patients scheduled for cataract surgery without other
ophthalmologic comorbidities were included. During surgery, continuous OCT
recordings were performed to measure and score swirling lens fragments that came
into contact with the corneal endothelium. Endothelial cell density (ECD) was
measured preoperatively and 1 month postoperatively. In addition, the central
corneal thickness and aqueous flare were measured preoperatively and 1 hour, 1
day, and 1 month postoperatively. RESULTS: Continuous intraoperative OCT video
recordings showed 104 swirling lens fragments in 40 eyes that came into contact
with the corneal endothelium. A mean of 2.6 lens fragments (range 0 to 6) that
came into contact were observed per eye. Small fragments and fragments touching
the center of the endothelium had a significantly greater effect on postoperative
ECD than other fragment parameters. The predictive power of the fragment score on
ECD was found to be moderate (r(2) = 0.6). CONCLUSIONS: Small swirling lens
fragments touching the center of the corneal endothelium had a significant
influence on ECD. With the newly developed fragment score, it was possible to
predict the operative endothelial cell loss. FINANCIAL DISCLOSURE: None of the
authors has a financial or proprietary interest in any material or method
mentioned.
PMID- 27492103
TI - Immunohistochemical characteristics of the vitreolenticular interface in
congenital unilateral posterior cataract.
AB - PURPOSE: To gain insight into the histology of the vitreolenticular interface in
congenital unilateral posterior cataract. SETTING: Antwerp University Hospital,
Department of Ophthalmology, Edegem, and the University of Antwerp, Faculty of
Medicine and Health Sciences, Antwerp, Belgium. DESIGN: Prospective case study.
METHODS: Samples of the posterior lens capsule of patients with congenital
posterior cataract (including opaque plaque on the anterior and adhesion to the
vitreous on the posterior surface) were collected during the posterior
capsulorhexis procedure. Staining for collagen types II and IV was performed
using indirect immunohistochemistry. Results were compared with those of control
posterior lens capsules of 3 children and 3 adults. RESULTS: Samples were
collected from 3 patients. All posterior lens capsules contained collagen type
IV. Samples from congenital posterior cataract patients all showed a narrow band
of collagen type II on the outer surface, indicating strong adherence of the
anterior hyaloid membrane to the center of the posterior lens capsule.
Surprisingly, collagen type II was also found in the posterior capsule plaques.
Collagen type II was not found in any control posterior lens capsule. CONCLUSION:
The adherence of collagen type II to the center of the posterior lens capsule
histologically supports the hypothesis that this subgroup of congenital cataract
hints at an abnormality at the vitreolenticular interface. FINANCIAL DISCLOSURE:
None of the authors has a financial or proprietary interest in any material or
method mentioned.
PMID- 27492104
TI - Higher-order aberrations 1 year after corneal collagen crosslinking for
keratoconus and their independent effect on visual acuity.
AB - PURPOSE: To evaluate the effect of corneal collagen crosslinking (CXL) in
progressive keratoconus patients on higher-order aberrations (HOAs) and the
effect of change in HOAs on visual acuity between baseline and 1 year after CXL.
SETTING: Tertiary academic referral center, Utrecht, the Netherlands. DESIGN:
Prospective cohort study. METHODS: This study included consecutive keratoconus
patients who were treated with epithelium-off CXL and followed for a minimum of 1
year. The following corneal HOAs were measured with Scheimpflug tomography
(Pentacam HR type 70900): coma, trefoil, spherical aberration, and total corneal
HOAs. A 2-tailed paired-samples t test was used to compare baseline and
postoperative aberrations. Multivariable linear regression was applied to assess
the independent effects of HOA subtypes on changes in uncorrected (UDVA) and
corrected (CDVA) distance visual acuity. RESULTS: Overall, the degree of corneal
HOAs in the patient cohort (N = 187) was relatively unchanged after CXL, with a
mean change of -1.34% (P = .272). Horizontal coma contributed most to the total
amount of HOAs but was virtually unchanged on average. The HOA subtype of
spherical aberrations decreased significantly (-15.68%) (P < .001). There was no
effect of the change in HOAs on the change in CDVA; however, there was a
significant effect of the change in horizontal coma on the change in UDVA (P =
.003; B -0.475). CONCLUSIONS: Corneal HOAs in general were relatively unchanged
from baseline to 1 year after CXL in eyes with progressive keratoconus. A change
in horizontal coma had a strong and independent effect on UDVA. FINANCIAL
DISCLOSURE: None of the authors has a financial or proprietary interest in any
material or method mentioned.
PMID- 27492105
TI - Natural history of corneal haze after corneal collagen crosslinking in
keratoconus using Scheimpflug analysis.
AB - PURPOSE: To analyze corneal haze after corneal collagen crosslinking (CXL) for
progressive keratoconus using Scheimpflug densitometry. SETTING: Auckland
District Health Board, Auckland, New Zealand. DESIGN: Prospective randomized
controlled study. METHODS: Both eyes of all patients were examined preoperatively
and 1, 3, 6, and 12 months postoperatively. One eye of each patient was treated
with corneal CXL, with the contralateral eye serving as the control. Examinations
included uncorrected distance visual acuity and corrected distance visual acuity
(CDVA), slitlamp biomicroscopy, and Scheimpflug tomography (Pentacam). RESULTS:
Thirty-six eyes of 36 patients were enrolled. The mean preoperative corneal
densitometry was 19.0 +/- 3.2 (SD). Postoperatively, the mean densitometry peaked
at 1 month, decreasing to baseline level after 6 months without application of
topical corticosteroids. The development of haze was significant compared with
the contralateral untreated eyes (P < .01). The anterior (120 MUm) and inner
(central 0.0 to 2.0 mm) zones of the cornea had the highest densitometry after
treatment. Lower preoperative central corneal thickness (CCT) was significantly
correlated with higher corneal densitometry (P = .03). However, the preoperative
CCT, keratometry, and astigmatism did not influence the difference in
densitometry between the treated eyes and untreated eyes. There was no evidence
of a relationship between densitometry and CDVA (P = .30). CONCLUSIONS: After
corneal CXL, patients with keratoconus developed transient corneal haze in the
anterior central cornea that might not require specific treatment. Thin corneas
were associated with higher densitometry; thus, there might be a greater
expectancy of corneal haze in patients with advanced keratoconus. FINANCIAL
DISCLOSURE: None of the authors has a financial or proprietary interest in any
material or method mentioned.
PMID- 27492106
TI - Outcome of primary intraocular lens implantation in infants: Complications and
rates of additional surgery.
AB - PURPOSE: To study the requirement of additional surgery and adverse events in
infants having primary intraocular lens (IOL) implantation. SETTING: Tertiary
care institute, Chandigarh, India. DESIGN: Prospective observational
noncomparative case series. METHODS: Infants who had phacoaspiration, primary
posterior capsulotomy, anterior vitrectomy, and primary IOL implantation were
evaluated for complications and the need for additional surgery over a 3-year
period. The main outcome measures were the rate of complications, adverse events,
and need for additional surgery. RESULTS: Sixty infants (100 eyes) with a mean
age of 7.13 months +/- 2.32 (SD) (range 3 to 12 months) were studied. The mean
follow-up was 41.2 +/- 3.5 months. Indication of additional surgery included
visual axis opacification in 13 eyes, pupillary membrane/IOL decentration in 4
eyes, and iris prolapse in 4 eyes. Adverse events included pigment on the IOL in
14 eyes and iridolenticular adhesions in 9 eyes. Ocular hypertension was observed
in 2 eyes. The IOL was placed in sulcus or by optic capture in 14 eyes. There was
no difference in additional surgery and adverse events between infants aged 6
months or younger versus those older than 6 months (P = .734). CONCLUSION: There
was a low incidence of adverse events and additional surgery requirement in
infants who had cataract surgery with primary IOL implantation. FINANCIAL
DISCLOSURE: None of the authors has a financial or proprietary interest in any
material or method mentioned.
PMID- 27492107
TI - Evaluation of long-term biocompatibility and capsular bag opacification with a
new silicone-polyimide plate-type intraocular lens in the rabbit model.
AB - PURPOSE: To evaluate the long-term biocompatibility and safety of the new SC9
intraocular lens (IOL) after implantation in rabbit eyes, in accordance with the
requirements of the International Organization for Standardization 11979-5, Annex
G:2006(E). SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City,
Utah, USA. DESIGN: Experimental study. METHODS: Bilateral phacoemulsification was
performed on 9 New Zealand white rabbits; 1 eye received the test IOL and the
contralateral eye received a commercially available plate-type silicone control
IOL (AA4204VL). Two rabbits were humanely killed at 2 months and the remaining at
6 months. After gross examination of the eyes from the posterior Miyake-Apple
view, select IOLs were explanted and had surface staining for implant cytology.
All globes were then sectioned and processed for complete histopathologic
examination. RESULTS: Overall uveal biocompatibility was similar between the test
IOLs and control IOLs throughout the study. The mean posterior capsule
opacification at 6 months was 0.8 +/- 0.27 (SD) in the test group and 4.0 +/- 0
in the control group (P = .001, t test: paired 2-sample for means). The mean
posterior synechiae formation at 6 months was 1.28 +/- 1.25 in the test group and
2.71 +/- 0.75 in the control group (P = .01). A histopathologic examination
confirmed the relative lack of capsule opacification in the study eyes compared
with the control eyes and the absence of untoward inflammatory reaction or
toxicity in all eyes. CONCLUSION: The new IOL maintained an open capsular bag
secondary to its design, which appeared to prevent overall capsular bag
opacification and retain uveal and capsule biocompatibility. FINANCIAL
DISCLOSURE: None of the authors has a financial or proprietary interest in any
material or method mentioned.
PMID- 27492108
TI - Effects of genipin corneal crosslinking in rabbit corneas.
AB - PURPOSE: To evaluate the effect of genipin, a natural crosslinking agent, in
rabbit eyes. SETTING: Department of Ophthalmology, Universidad Nacional de
Colombia Centro de Tecnologia Oftalmica, Bogota, Colombia. DESIGN: Experimental
study. METHODS: Ex vivo rabbit eyes (16; 8 rabbits) were treated with genipin
1.00%, 0.50%, and 0.25% for 5 minutes with a vacuum device to increase corneal
permeability. Penetration was evaluated using Scheimpflug pachymetry (Pentacam).
In the in vivo model (20 rabbits; 1 eye treated, 1 eye with vehicle), corneas
were crosslinked with genipin as described. Corneal curvature, corneal
pachymetry, and intraocular pressure (IOP) assessments as well as slitlamp
examinations were performed 0, 7, 30, and 60 days after treatment. RESULTS: In
the ex vivo model, Scheimpflug pachymetry showed deep penetration in the rabbit
corneas with an increase in corneal density and a dose-dependent relationship.
Corneal flattening was observed in treated eyes (mean 4.4 diopters +/- 0.5 [SD])
compared with the control eyes. Pachymetry and IOP were stable in all
evaluations. No eye showed toxicity in the anterior chamber or in the lens.
CONCLUSIONS: Corneal crosslinking induced by genipin produced significant
flattening of the cornea with no toxicity in rabbit eyes. This crosslinking could
be useful in the treatment of corneal ectasia and in the modification of corneal
curvature. FINANCIAL DISCLOSURE: None of the authors has a financial or
proprietary interest in any material or method mentioned.
PMID- 27492109
TI - Clinical outcomes of small-incision lenticule extraction and femtosecond laser
assisted wavefront-guided laser in situ keratomileusis.
AB - Small-incision lenticule extraction and wavefront-guided femtosecond-assisted
laser in situ keratomileusis (LASIK) provide good visual outcomes and an
efficacious correction of myopia or myopic astigmatism with similar levels of
safety. Some differences in predictability and the percentage of eyes gaining
lines of corrected distance visual acuity are present. A higher level of coma is
present after small-incision lenticule extraction, with no clear differences
between techniques in spherical aberration. Better contrast sensitivity is
achieved in the early postoperative period after wavefront-guided femtosecond
laser-assisted LASIK, possibly because of less intrastromal light backscattering
and Bowman layer microdistortions. Corneal sensitivity decreased less after small
incision lenticule extraction because of less severe decrease in subbasal nerve
density, which has a significant effect on symptomatology and dry-eye tests (P <
.05). Significant corneal biomechanical changes occurred after both techniques (P
< .05), with no scientific evidence supporting the superiority of 1 technique
over the other. FINANCIAL DISCLOSURE: Dr. Pinero received an unrestricted
educational grant from Abbott Medical Optics, Inc. Neither author has a financial
or proprietary interest in any material or method mentioned.
PMID- 27492110
TI - Cataract in pseudohypoparathyroidism.
AB - A 22-year-old white man presented with photopsia of 3-year duration despite a
corrected distance visual acuity of 20/20 in both eyes. Ophthalmic examination
revealed multiple irregularly shaped white cortical opacifications of the lens in
both eyes but no other significant ocular findings. One year after the photopsia
onset, the patient experienced an episode of seizures with generalized tonic
clonic movements. Neurological follow-up examination demonstrated extensive brain
calcification in the basal ganglia and frontal lobes, leading to a diagnosis of
pseudohypoparathyroidism. Pseudohypoparathyroidism is a rare condition, and there
are few reports of ocular findings with this underlying pathology. Our findings
clearly demonstrate that even relatively unremarkable ocular signs can lead to
diagnosis of severe systemic diseases. Therefore, the cataract surgeon should be
aware of these conditions before removing the lens. FINANCIAL DISCLOSURE: None of
the authors has a financial or proprietary interest in any material or method
mentioned.
PMID- 27492111
TI - Cataractous mountain on the corneal horizon: Swept-source optical coherence
tomography.
PMID- 27492112
TI - Tetracaine-enhanced transepithelial corneal collagen crosslinking.
PMID- 27492113
TI - Reply.
PMID- 27492115
TI - A Modern Menagerie of Mammalian Malaria.
AB - Malaria parasites belong to the diverse apicomplexan order Haemospororida and use
a variety of vertebrate and dipteran hosts worldwide. Recently, the utilization
of molecular methods has resulted in a burst of newly discovered and rediscovered
taxa infecting mammalian hosts, particularly in apes, ungulates, and bats.
Additional study of these diverse mammal-infecting taxa is crucial for better
understanding the evolutionary history of malaria parasites, especially given
that most previous comparative phylogenetic analyses have tended to use both
limited taxon sampling and a small set of genetic loci, resulting in weakly
supported (and sometimes hotly contested) hypotheses. The ability to generate
genomic data from these mammalian parasites, even from subpatent infections, will
open up exciting prospects for research on malaria parasites.
PMID- 27492114
TI - Ammonia stress under high environmental ammonia induces Hsp70 and Hsp90 in the
mud eel, Monopterus cuchia.
AB - The obligatory air-breathing mud eel (Monopterus cuchia) is frequently being
challenged with high environmental ammonia (HEA) exposure in its natural
habitats. The present study investigated the possible induction of heat shock
protein 70 and 90 (hsp70, hsc70, hsp90alpha and hsp90beta) genes and more
expression of Hsp70 and Hsp90 proteins under ammonia stress in different tissues
of the mud eel after exposure to HEA (50 mM NH4Cl) for 14 days. HEA resulted in
significant accumulation of toxic ammonia in different body tissues and plasma,
which was accompanied with the stimulation of oxidative stress in the mud eel as
evidenced by more accumulation of malondialdehyde (MDA) and hydrogen peroxide
(H2O2) during exposure to HEA. Further, hyper-ammonia stress led to significant
increase in the levels of mRNA transcripts for inducible hsp70 and hsp90alpha
genes and also their translated proteins in different tissues probably as a
consequence of induction of hsp70 and hsp90alpha genes in the mud eel. However,
hyper-ammonia stress was neither associated with any significant alterations in
the levels of mRNA transcripts for constitutive hsc70 and hsp90beta genes nor
their translated proteins in any of the tissues studied. More abundance of Hsp70
and Hsp90alpha proteins might be one of the strategies adopted by the mud eel to
defend itself from the ammonia-induced cellular damages under ammonia stress.
Further, this is the first report of ammonia-induced induction of hsp70 and
hsp90alpha genes under hyper-ammonia stress in any freshwater air-breathing
teleost.
PMID- 27492116
TI - A systematic review of tranexamic acid in hip fracture surgery.
AB - AIM: To systematically examine and quantify the efficacy and safety of tranexamic
acid in hip fracture surgery. METHODS: A systematic literature search was
conducted using Medline, EMBASE, AMED, CiNAHL, and the Cochrane Central Registry
of Controlled Trials. Two assessors independently screened search outputs for
potentially relevant articles which met the eligibility criteria. The primary
outcome measure was requirement of post-operative blood transfusion. Risk of bias
assessment was performed using the Cochrane Collaboration's risk of bias tool for
randomized controlled trials (RCTs) and the ROBINS-I tool for observational
studies. Meta-analysis was performed to estimate risk ratio (RR), risk difference
(RD) and mean difference (MD) values for dichotomous and continuous data
outcomes, respectively. The interpretation of each outcome was made using the
GRADE approach. RESULTS: Of 102 studies identified, seven met the inclusion
criteria including a total of 770 participants (TXA: 341; Control: 429). On meta
analysis, intravenous TXA resulted in a 46% risk reduction in blood transfusion
requirement compared to a placebo/control group (RR: 0.54; 95% CI: 0.35-0.85; I2
: 78%; Inconsistency (chi2 ) P = <0.0001; n = 750). There was also a
significantly higher post-operative haemoglobin for TXA versus placebo/control
(MD: 0.81; 95% CI: 0.45-1.18; I2 : 46%; Inconsistency (chi2 ) P = 0.10; n = 638).
There was no increased risk of thromboembolic events (RD: 0.01; 95% CI: -0.03,
0.05; I2 : 68%; Inconsistency (chi2 ) P = 0.007, n = 683). CONCLUSION: There is
moderate quality evidence that TXA reduces blood transfusion in hip fracture
surgery, with low quality evidence suggesting no increased risk of thrombotic
events. These findings are consistent with TXA use in other orthopaedic
procedures.
PMID- 27492117
TI - Social Media and Internet Resources for Patients with Blastic Plasmacytoid
Dendritic Cell Neoplasm (BPDCN).
AB - The incorporation of Internet resources and the use of social media among
patients, clinicians, advocates, and researchers in the field of hematology and
oncology are growing in importance. Utilization of online information sharing is
rising, especially among those involved in rare blood cancer fields, which have
generally featured a paucity of reliable, updated information. In particular,
blastic plasmacytoid dendritic cell neoplasm (BPDCN), an uncommon, but highly
aggressive hematologic malignancy, is one example of a cancer with limited
information readily available to the general public. The infrequent incidence of
BPDCN, the challenges in recognizing the disease and making a clinico-pathologic
diagnosis, and the lack of standard therapies are some of the reasons accounting
for the dearth of expert opinion, scientific publications and discussion, and
accessibility of online information for patients. This article highlights social
media and Internet sources available for patients and other healthcare
stakeholders in the field of BPDCN and discusses our efforts to increase
awareness and propagation of BPDCN electronic resources, including the founding
of an online Twitter community, #BPDCN.
PMID- 27492118
TI - Social Media and Myeloproliferative Neoplasms (MPN): Analysis of Advanced Metrics
From the First Year of a New Twitter Community: #MPNSM.
AB - The social media platform Twitter has provided the hematology/oncology community
with unprecedented, novel methods of interpersonal communication and increased
ability for the dissemination of important updates in a rapidly moving field. The
advent, and subsequent success, of disease-specific Twitter communities have
further enabled interested healthcare stakeholders to become quickly organized
around a unique set of rare medical conditions, such as hematologic malignancies,
that, historically, generally lack large amounts of reliable online information.
One example is the Twitter community #MPNSM (myeloproliferative neoplasms on
social media), which was started approximately one and half years ago and has
served as a recognized venue for discussion among many members of the MPN
community, including patients, researchers, providers, and advocacy
organizations. This article will focus on understanding the impact of the
founding of this community via the analysis of advanced Twitter metrics of user
experience, from the first year of use for this novel healthcare hashtag.
PMID- 27492119
TI - Identification and expression analysis of IkappaB and NF-kappaB genes from
Cyclina sinensis.
AB - With the increasing economic importance of Cyclina sinensis aquaculture, interest
in its defense mechanisms against pathogenic infection has grown in recent years.
Inhibitor of nuclear factor-kappaB (IkappaB) and nuclear factor-kappaB (NF
kappaB) are proteins with central roles in many important physiological and
pathological processes, such as innate immune responses. In this study, we
identified CsIkappaB and CsNF-kappaB genes from a C. sinensis transcriptome
library. In healthy adult clams, CsIkappaB and CsNF-kappaB genes were widely
expressed in various tissues and highly expressed in hemocytes. Further, the
expression levels of these genes were significantly increased in hemocytes
challenged by Vibrio anguillarum, Micrococcus luteus and poly I:C. Inhibition of
CsMyD88 expression by RNAi technology significantly altered the mRNA expression
patterns of CsIkappaB and CsNF-kappaB as measured using quantitative real-time
PCR. These results collectively indicated that the NF-kappaB signaling pathway,
including CsIkappaB and CsNF-kappaB genes, might be involved in early innate
immune responses and may be regulated by a MyD88-dependent signaling pathway in
C. sinensis.
PMID- 27492120
TI - A high-mobility group box 1 that binds to DNA, enhances pro-inflammatory
activity, and acts as an anti-infection molecule in black rockfish, Sebastes
schlegelii.
AB - High-mobility group box (HMGB) 1 is a chromosomal protein that plays critical
roles in DNA transcription, replication and repair. In addition, HMGB1 functions
as a pro-inflammatory molecule in many vertebrates and invertebrates. In
teleosts, very limited studies of HMGB1 have been reported. In this study, we
identified a HMGB1 homologue (SsHMGB1) from black rockfish (Sebastes schlegelii)
and analyzed its structure, expression and biological function. The open reading
frame of SsHMGB1 is 621 bp, with a 5'-untranslated region (UTR) of 62 bp and a 3'
UTR of 645 bp. SsHMGB1 contains two typical HMG boxes and an acidic C-terminal
tail. The deduced amino acid sequence of SsHMGB1 shares the highest overall
identity (89.4%) with the HMGB1 of Anoplopoma fimbria. The expression of SsHMGB1
occurred in multiple tissues and was highest in the brain. Moreover, the mRNA
level of SsHMGB1 in head kidney (HK) macrophages could be induced by Listonella
anguillarum in a time-dependent manner. Recombinant SsHMGB1 purified from
Escherichia coli (i) bound DNA fragments in a dose-dependent manner; and (ii)
induced the expression of cytokines in HK macrophages, including a significant
increase in TNF-alpha activity and enhanced mRNA level of TNF13B and IL-1 beta,
which are known to be involved in antibacterial defense; moreover, (iii)
significantly improved the macrophage bactericidal activity together with reduced
pathogen dissemination and replication of bacteria in fish kidney. These results
indicated that SsHMGB1 is a novel HMGB1 that possesses apparent immunoregulatory
properties and is likely to be involved in fighting bacterial infection.
PMID- 27492121
TI - The Dorsal/miR-1959/Cactus feedback loop facilitates the infection of WSSV in
Litopenaeus vannamei.
AB - miR-1959, a novel microRNA identified from Litopenaeus vannamei, mediates a
positive feedback loop between Dorsal and Cactus that can continuously maintain
the activation of the NF-kappaB pathway. It has been known that miR-1959 is
involved in antibacterial immunity in shrimp, but its function in antiviral
responses is still unknown. In this study, we focused on the role of miR-1959 in
infection of white spot syndrome virus (WSSV), the major viral pathogen in shrimp
worldwide. The expression of miR-1959 in shrimp hemocytes, gill, and
hepatopancreas was significantly up-regulated upon WSSV infection. Dual
luciferase reporter assays demonstrated that miR-1959 could enhance the activity
of the promoter of WSSV immediate early gene ie1. In vivo experiments also showed
that inhibition of miR-1959 led to decrease of the mortality of WSSV-infected
shrimp and the genome copies of WSSV in tissues, meanwhile the expression of WSSV
ie1 and VP28 genes was down-regulated. In contrast, increase of the miR-1959
level in shrimp by injection of miR-1959 mimics produced opposite results. These
suggested that the Dorsal/miR-1959/Cactus feedback loop could favor the infection
of WSSV in shrimp. Thus, our study helps further reveal the interaction between
WSSV and shrimp immune system.
PMID- 27492122
TI - Glucomannan's protective effect on the virulence of Vibrio splendidus in pacific
oyster.
AB - We examine the effect of Glucomannan, extracted from Candida utilis yeast, on
immune parameters and resistance to Vibrio splendidus of Crassostreagigas. Our
results showed that Glucomannan was a successful anti-adhesive molecule; it
exhibited a stronger inhibitory effect on adhesion of Vibrio splendidus in
infected Crassostreagigas. Vibrio splendidus viable cells number declined after
incubation with Glucomannan. Furthermore, the Glucomannan diet showed higher
activity to trigger the immune response against bacteria. Glucomannan
applications, in biological control of seafood associated pathogens can be an
alternative solution, providing consumer with a product of good quality owing to
the use of 40 non-toxic compounds. Based on our results, Glucomannan could be
used as a bio-protective culture in oyster's depuration to prevent Vibrio
splendidus growth.
PMID- 27492123
TI - Pinocembrin attenuates lipopolysaccharide-induced inflammatory responses in Labeo
rohita macrophages via the suppression of the NF-kappaB signalling pathway.
AB - Pinocembrin is a flavonoid that has been reported to exhibit various
pharmacological and biological activities including antimicrobial, antioxidant,
and anti-inflammatory. To explore the anti-inflammatory activity of pinocembrin
in a fish cell line, we investigated its ability to regulate the inflammatory
mediators elevated by lipopolysaccharide (LPS) in Labeo rohita head-kidney (HK)
macrophages. HK macrophages of L. rohita were treated with LPS (1 MUg mL(-1)) in
the presence or absence of pinocembrin. We examined the inhibitory effect of
pinocembrin on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2)
production. The inhibitory effect of pinocembrin on nitric oxide synthase (iNOS)
and cyclooxygenase-2 (COX-2) was investigated by RT-PCR and western blot. The
effect of pinocembrin on pro-inflammatory cytokines (tumour necrosis factor alpha
(TNF-alpha) and interleukin-1beta (IL-1beta)) and anti-inflammatory cytokine IL
10 was investigated by ELISA and RT-PCR. The phosphorylation of three mitogen
activated protein kinases (MAPKs) ERK, JNK, and p38 was analysed by western blot.
Pinocembrin inhibited LPS-induced productions of NO and PGE2, and also markedly
inhibited TNF-alpha, IL-1beta, iNOS, and COX-2 production in a concentration
dependent manner. In addition, TNF-alpha and IL-1beta mRNA expression levels
decreased significantly, while IL-10 mRNA expression increased (P < 0.05) with
pinocembrin pre-treatment. RT-PCR and western blot analysis showed that
pinocembrin decreased both the mRNA and protein expression levels of LPS-induced
iNOS and COX-2 in HK macrophages. Pinocembrin suppressed the phosphorylation of
MAPK in LPS-stimulated HK macrophages. Further, pinocembrin significantly
inhibited LPS-induced NF-kappaB transcriptional activity via the attenuation of
IkappaBalpha degradation. Taken together, pinocembrin reduced the levels of pro
inflammatory mediators, such as iNOS, COX-2, TNF-alpha, and IL-1beta, by
inhibiting NF-kappaB activation via the suppression of ERK and p38
phosphorylation, and by attenuating the degradation of IkappaBalpha. These
results suggest that pinocembrin is a potential novel candidate for the treatment
of inflammatory conditions in L. rohita macrophages.
PMID- 27492124
TI - Transcriptome analysis of mud crab (Scylla paramamosain) gills in response to Mud
crab reovirus (MCRV).
AB - Mud crab (Scylla paramamosain) is an economically important marine cultured
species in China's coastal area. Mud crab reovirus (MCRV) is the most important
pathogen of mud crab, resulting in large economic losses in crab farming. In this
paper, next-generation sequencing technology and bioinformatics analysis are used
to study transcriptome differences between MCRV-infected mud crab and normal
control. A total of 104.3 million clean reads were obtained, including 52.7
million and 51.6 million clean reads from MCRV-infected (CA) and controlled (HA)
mud crabs respectively. 81,901, 70,059 and 67,279 unigenes were gained
respectively from HA reads, CA reads and HA&CA reads. A total of 32,547 unigenes
from HA&CA reads called All-Unigenes were matched to at least one database among
Nr, Nt, Swiss-prot, COG, GO and KEGG databases. Among these, 13,039, 20,260 and
11,866 unigenes belonged to the 3, 258 and 25 categories of GO, KEGG pathway, and
COG databases, respectively. Solexa/Illumina's DGE platform was also used, and
about 13,856 differentially expressed genes (DEGs), including 4444 significantly
upregulated and 9412 downregulated DEGs were detected in diseased crabs compared
with the control. KEGG pathway analysis revealed that DEGs were obviously
enriched in the pathways related to different diseases or infections. This
transcriptome analysis provided valuable information on gene functions associated
with the response to MCRV in mud crab, as well as detail information for
identifying novel genes in the absence of the mud crab genome database.
PMID- 27492125
TI - Suppressor of cytokine signaling 2 (SOCS2) negatively regulates the expression of
antimicrobial peptides by affecting the Stat transcriptional activity in shrimp
Marsupenaeus japonicus.
AB - The suppressor of cytokine signaling (SOCS) family is a kind of negative
regulators in the Janus kinase/signal transducer and activator of transcription
(Jak/Stat) pathway in mammals and Drosophila. In kuruma shrimp, Marsupenaeus
japonicus, SOCS2 is identified and its expression can be stimulated by
peptidoglycan and polycytidylic acid. However, if SOCS2 participates in
regulating Jak/Stat pathway in shrimp still needs further study. In this study,
SOCS2 with Src homology 2 domain and SOCS box was identified in kuruma shrimp, M.
japonicus. SOCS2 existed in hemocytes, heart, hepatopancreas, gills, stomach, and
intestine, the expression of SOCS2 was upregulated significantly in the hemocytes
and intestine of shrimp challenged with Vibrio anguillarum at 6 h. To analyze
SOCS2 function in shrimp immunity, bacterial clearance and survival rate were
analyzed after knockdown of SOCS2 in shrimp challenged with V. anguillarum.
Results showed that bacterial clearance increased, and the survival rate improved
significantly comparing with controls. The SOCS2 was expressed in Escherichia
coli and the recombinant SOCS2 was injected into shrimp, and Stat phosphorylation
and translocation were analyzed. The result showed that "overexpression" of SOCS2
declined Stat phosphorylation level and inhibited Stat translocation into the
nucleus. After knockdown of SOCS2 in shrimp prior to V. anguillarum infection,
the expression level of antimicrobial peptides, including anti-lipopolysaccharide
factors C1, C2 and D1, and Crustin I was upregulated significantly, and the
expression of the AMPs was declined after recombinant SOCS2 injection. The SOCS2
expression was also decreased in Stat-knockdown shrimp challenged by V.
anguillarum at 6 and 12 h. Therefore, SOCS2 negatively regulates the AMP
expression by inhibiting Stat phosphorylation and translocation into nucleus in
shrimp, meanwhile, SOCS2 expression was also regulated by Jak/Stat pathway.
PMID- 27492126
TI - Resonance-Assisted Hydrogen Bonding as a Driving Force in Synthesis and a Synthon
in the Design of Materials.
AB - Resonance-assisted hydrogen bonding (RAHB), a concept introduced by Gilli and co
workers in 1989, concerns a kind of intramolecular H-bonding strengthened by a
conjugated pi-system, usually in 6-, 8-, or 10-membered rings. This Review
highlights the involvement of RAHB as a driving force in the synthesis of
organic, coordination, and organometallic compounds, as a handy tool in the
activation of covalent bonds, and in starting moieties for synthetic
transformations. The unique roles of RAHB in molecular recognition and switches,
E/Z isomeric resolution, racemization and epimerization of amino acids and chiral
amino alcohols, solvatochromism, liquid-crystalline compounds, and in synthons
for crystal engineering and polymer materials are also discussed. The Review can
provide practical guidance for synthetic chemists that are interested in
exploring and further developing RAHB-assisted synthesis and design of materials.
PMID- 27492127
TI - Middle fascicle as a common retrograde limb in two left upper septal
interfascicular reentrant ventricular tachycardias: a case report.
PMID- 27492128
TI - Biological Activities of Triterpenoids and Phenolic Compounds from Myrica
cerifera Bark.
AB - Seven triterpenoids, 1 - 7, two diarylheptanoids, 8 and 9, four phenolic
compounds, 10 - 13, and three other compounds, 14 - 16, were isolated from the
hexane and MeOH extracts of the bark of Myrica cerifera L. (Myricaceae). Among
these compounds, betulin (1), ursolic acid (3), and myricanol (8) exhibited
cytotoxic activities against HL60 (leukemia), A549 (lung), and SK-BR-3 (breast)
human cancer cell lines (IC50 3.1 - 24.2 MUm). Compound 8 induced apoptotic cell
death in HL60 cells (IC50 5.3 MUm) upon evaluation of the apoptosis-inducing
activity by flow cytometric analysis and by Hoechst 33342 staining method.
Western blot analysis on HL60 cells revealed that 8 activated caspases-3, -8, and
-9 suggesting that 8 induced apoptosis via both mitochondrial and death receptor
pathways in HL60. Upon evaluation of the melanogenesis-inhibitory activity in B16
melanoma cells induced with alpha-melanocyte-stimulating hormone (alpha-MSH),
erythrodiol (7), 4-hydroxy-2-methoxyphenyl beta-d-glucopyranoside (13), and butyl
quinate (15) exhibited inhibitory effects (65.4 - 86.0% melanin content) with no,
or almost no, toxicity to the cells (85.9 - 107.4% cell viability) at 100 MUm
concentration. In addition, 8, myricanone (9), myricitrin (10), protocatechuic
acid (11), and gallic acid (12) revealed potent DPPH radical-scavenging
activities (IC50 6.9 - 20.5 MUm).
PMID- 27492129
TI - Highly Efficient Synthesis of Fructooligosaccharides by Extracellular
Fructooligosaccharide-Producing Enzymes and Immobilized Cells of Aspergillus
aculeatus M105 and Purification and Biochemical Characterization of a
Fructosyltransferase from the Fungus.
AB - In this work, Aspergillus aculeatus M105 was obtained to produce high
extracellular fructooligosaccharide-producing enzyme activity. The maximum yields
of fructooligosaccharides produced by its extracellular enzymes and immobilized
cells were 67.54 and 65.47% (w/w), respectively. A fructosyltransferase (FTase),
AaFT32A, was purified from M105. The optimal pH and temperature of AaFT32A were
pH 5.0-6.0 and 65 degrees C, respectively. The Km, Vmax, and kcat values for the
transfructosylating activity of AaFT32A were 2267 mM, 1347 MUmol/min/mg protein,
and 1550.2 s(-1), respectively, and those values for the hydrolytic activity of
AaFT32A were 6.10 mM, 32.44 MUmol/min/mg protein, and 37.3 s(-1), respectively.
The sequence of AaFT32A deduced from the cloned gene shared 99.4% identity with a
FTase from Aspergillus japonicus CB05 and a fructofuranosidase from Aspergillus
niger and 96.5% identity with a FTase (Aspacl_37092) from A. aculeatus ATCC
16872. The fungal strain and its FTase may have potential applications in the
prebiotics industry.
PMID- 27492131
TI - Two Decades of Laccases: Advancing Sustainability in the Chemical Industry.
AB - Given the current state of environmental affairs and that our future on this
planet as we know it is in jeopardy, research and development into greener and
more sustainable technologies within the chemical and forest products industries
is at its peak. Given the global scale of these industries, the need for
environmentally benign practices is propelling new green processes. These
challenges are also impacting academic research and our reagents of interest are
laccases. These enzymes are employed in a variety of biotechnological
applications due to their native function as catalytic oxidants. They are about
as green as it gets when it comes to chemical processes, requiring O2 as their
only co-substrate and producing H2 O as the sole by-product. The following
account will review our twenty year journey on the use of these enzymes within
our research group, from their initial use in biobleaching of kraft pulps and for
fiber modification within the pulp and paper industry, to their current
application as green catalytic oxidants in the field of synthetic organic
chemistry.
PMID- 27492132
TI - Twenty-four cases of imported zika virus infections diagnosed by molecular
methods.
AB - Zika virus is an emerging flavivirus widely spreading through Latin America.
Molecular diagnosis of the infection can be performed using serum, urine and
saliva samples, although a well-defined diagnostic algorithm is not yet
established. We describe a series of 24 cases of imported zika virus infection
into Catalonia (northeastern Spain). Based on our findings, testing of paired
serum and urine samples is recommended.
PMID- 27492130
TI - Endothelial PDGF-CC regulates angiogenesis-dependent thermogenesis in beige fat.
AB - Cold- and beta3-adrenoceptor agonist-induced sympathetic activation leads to
angiogenesis and UCP1-dependent thermogenesis in mouse brown and white adipose
tissues. Here we show that endothelial production of PDGF-CC during white adipose
tissue (WAT) angiogenesis regulates WAT browning. We find that genetic deletion
of endothelial VEGFR2, knockout of the Pdgf-c gene or pharmacological blockade of
PDGFR-alpha impair the WAT-beige transition. We further show that PDGF-CC
stimulation upregulates UCP1 expression and acquisition of a beige phenotype in
differentiated mouse WAT-PDGFR-alpha(+) progenitor cells, as well as in human WAT
PDGFR-alpha(+) adipocytes, supporting the physiological relevance of our
findings. Our data reveal a paracrine mechanism by which angiogenic endothelial
cells modulate adipocyte metabolism, which may provide new targets for the
treatment of obesity and related metabolic diseases.
PMID- 27492133
TI - Characterization of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella,
Enterobacter, and Citrobacter obtained in environmental samples of a Tunisian
hospital.
AB - The assessment of the hospital environment as a reservoir of ESBL-producing
Enterobacteriaceae in Tunisian hospitals is scarcely analyzed, except for
Escherichia coli. The aim of this study was to evaluate the presence of ESBL
producing non-E. coli Enterobacteriaceae (ESBL-EbNoEc) in 300 samples of abiotic
surfaces and the hands of patients and staff of a Tunisian Hospital, and to
characterize the ESBL genes of the recovered isolates. ESBL-EbNoEc were recovered
in 28 of 300 (9.3%) analyzed samples and were identified as Klebsiella pneumoniae
(n= 11), Enterobacter cloacae (n=11), Citrobacter freundii (n=4) and Klebsiella
oxytoca (n=2). The bla genes identified by PCR and sequencing among the strains
were as follows: 11 K.pneumoniae strains [blaCTX-M-15+ blaTEM-1+ blaSHV-11 (n=6);
blaCTX-M-15+ blaTEM-1+ blaSHV-28 (n=3); blaCTX-M-15+ blaTEM-1+ blaSHV-1 (n=2)],
11 E. cloacae strains [blaCTX-M-15 (n=6); blaCTX-M-15+ blaTEM-1b (n=2); blaCTX-M
15+ blaTEM-1b+ blaOXA-1 (n=1);blaCTX-M-15+ blaOXA-1 (n=1);blaSHV-12 (n=1)], 4 C.
freundii strains [blaCTX-M-15] and 2 K. oxytoca strains [blaCTX-M-15 (n=1);
blaSHV-12 (n=1)]. The ISEcp1 and orf477 sequences were identified upstream and
downstream of the blaCTX-M-15 gene, respectively, in 3 K. pneumoniae and 3 E.
cloacae isolates. The PFGE analysis demonstrated three unrelated pulsotypes in K.
pneumoniae strains and five pulsotypes in E. cloacae. The uncontrolled
dissemination of ESBL-producing bacteria, even in the hospital environment, has
become a real problem and new strategies and hygienic rules are needed to stop
this bacterial dissemination.
PMID- 27492134
TI - Postantifungal effect of caspofungin against the Candida albicans and Candida
parapsilosis clades.
AB - Killing and postantifungal effects could be relevant for the selection of optimal
dosing schedules. This study aims to compare time-kill and postantifungal effects
with caspofungin on Candida albicans (C. albicans, Candida dubliniensis, Candida
africana) and Candida parapsilosis (C. parapsilosis, Candida metapsilosis,
Candida orthopsilosis) clades. In the postantifungal effect experiments, strains
were exposed to caspofungin for 1 h at concentrations 0.12-8 MUg/mL. Time-kill
experiments were conducted at the same concentrations. Caspofungin exhibited a
significant and prolonged postantifungal effect (>37 h) with 2 MUg/mL against the
most strains of C. albicans clade. Against the C. parapsilosis clade, the
postantifungal effect was <12 h at 8 MUg/mL, except for two strains. Caspofungin
was fungicidal against C. albicans, C. dubliniensis and C. metapsilosis.
PMID- 27492135
TI - Use of Low Dose Ziconotide as First-Line Intrathecal Monotherapy.
AB - BACKGROUND: Ziconotide use in intrathecal drug therapy (IDT) has been limited by
dosing related side effects. We examine our experience with ziconotide as a first
line IDT monotherapy in patients with chronic pain and present our low and slow
dosing algorithm aimed at reducing these patient experienced side effects while
adequately managing pain. METHODS: We retrospectively reviewed demographics,
dosing, and outcomes of 15 consecutive patients with complete three-month data
sets implanted with intrathecal pain pumps more than three years utilizing
ziconotide as a first-line monotherapy. RESULTS: Ziconotide response was assessed
at visit 5 (69 +/- 10 days) and responders were characterized by having 30% or
greater improvement in numerical rating scale scores (n = 7), or activities of
daily living (ADL) (n = 7). Eight of our patients had a response in at least one
measure (53%). In our eight responders, NRS score decreased from 8.4 +/- 0.7 at
baseline (consult visit) to 2.4 +/- 1.0 at 2.6 months and 4.0 +/- 1.3 at most
recent follow-up, mean of 12.9 months after implant. We noted that our responders
tended to have neuropathic pain with an objective etiology. Initial dosing in 12
patients was 1.2 mcg/day (range for the other three patients was 0.6-1.4).
Following initial dosing, visits were at 2-4 week intervals with mean titration
doses between 1.1 and 2.8 mcg/day. Slight dizziness in two patients and transient
urinary retention in one patient occurred, all resolving with dose reduction. No
patients had discontinued use at three-month follow-up. DISCUSSION: We present
our experience with low and slow ziconotide IDT as a first-line monotherapy,
which showed no side effects resulting in discontinuation of the medication at
three-month follow-up. Using a conservative dosing strategy, we were able to
effectively treat 53% of patients.
PMID- 27492136
TI - The first porphyrin-subphthalocyaninatoboron(iii)-fused hybrid with unique
conformation and intramolecular charge transfer behavior.
AB - Porphyrin and subphthalocyaninatoboron(iii) chromophores have been fused through
a quinoxaline moiety, resulting in the first porphyrin
subphthalocyaninatoboron(iii)-fused hybrid with intramolecular charge transfer
from tetrapyrrole/tripyrrole chromophores to the quinoxaline moiety. The unique
plane-bowl molecular structure of this hybrid was revealed based on single
crystal X-ray diffraction analysis for the first time.
PMID- 27492137
TI - [Tibial defects and infected non-unions : Treatment results after Masquelet
technique].
AB - BACKGROUND: The treatment of non-unions with large bone defects or osteitis is a
major challenge in orthopedic and trauma surgery. A new concept of therapy is a
two-step procedure: Masquelet technique according to the diamond concept.
METHODS: Between February 2010 and June 2014, 55 patients with tibia non-unions
or infections were treated in a two-step Masquelet technique in our center. The
patients' average age was 48 (median 50; minimum 15-maximum 72) with an average
BMI (body mass index) of 28 (27; 18-52). There were 10 (18 %) female and 45 (82
%) male patients in the group. All study patients went through a follow up. Bone
healing and clinical functional data were collected, as well as data according to
subjective patient statements about pain and everyday limitations. RESULTS: In 42
cases (76.4 %) the outcome was a sufficient bony consolidation. On average, the
time to heal was 10.3 (8, 5; 3-40) months, defect gaps were 4 cm (3 cm; 0,6-26
cm), and on average the patients had had 6 (median 4; range 1-31) previous
operations . In all cases patients received osteosynthesis as well as a defect
filling with RIA (reamer-irrigator-aspirator), and growth factor BMP-7 (bone
morphogenetic protein-7). In 13 cases (23.6 %) there was no therapeutic success.
In the evaluation of the SF12 questionnaire the mental health score increased
from 47.4 (49.1; 27.6-65.7) to 49.8 (53.0; 28.7-69.4) and the well-being score
from 32.7 (32.7;16.9-55.7) to 36.6 (36.5; 24.6-55.9). CONCLUSION: The two-step
bone grafting method in the Masquelet technique used for tibia non-unions
according to the diamond concept is a promising treatment option. Its application
for tibia shaft non-unions with large bone defects or infections means a high
degree of safety for the patient.
PMID- 27492139
TI - Stanene: Atomically Thick Free-standing Layer of 2D Hexagonal Tin.
AB - Stanene is one of most important of 2D materials due to its potential to
demonstrate room temperature topological effects due to opening of spin-orbit
gap. In this pursuit we report synthesis and investigation of optical properties
of stanene up to few layers, a two-dimensional hexagonal structural analogue of
graphene. Atomic scale morphological and elemental characterization using HRTEM
equipped with SAED and EDAX detectors confirm the presence of hexagonal lattice
of Sn atoms. The position of Raman peak along with the inter-planar 'd' spacing
obtained from SAED for prepared samples are in good agreement with that obtained
from first principles calculations and confirm that the sheets are not (111)
alpha-Sn sheets. Further, the optical signature calculated using density
functional theory at ~191 nm and ~233 nm for low buckled stanene are in
qualitative agreement with the measured UV-Vis absorption spectrum. AFM
measurements suggest interlayer spacing of ~0.33 nm in good agreement with that
reported for epitaxial stanene sheets. No traces of oxygen were observed in the
EDAX spectrum suggesting the absence of any oxidized phases. This is also
confirmed by Raman measurements by comparing with oxidized stanene sheets.
PMID- 27492138
TI - Conditional Deletion of Smad1 Ameliorates Glomerular Injury in Progressive
Glomerulonephritis.
AB - Matrix expansion and cell proliferation are concomitantly observed in various
glomerular injuries. However, the molecular mechanisms responsible for these
changes have not been fully elucidated. We have reported that Smad1 is a key
signalling molecule that regulates the transcription of type IV collagen (Col4)
in mesangial matrix expansion and is thereby involved in glomerular injury in an
acute model of glomerulonephritis. In this study, we addressed the role of Smad1
signalling in accelerated nephrotoxic nephritis (NTN), a model of progressive
glomerulonephritis, using conditional deletion of Smad1 in Rosa26CreERT2 mice
(Smad1-CKO). Mesangial matrix expansion in the Smad1-CKO mice with NTN was
significantly inhibited compared with that in wild type mice with NTN, which was
consistent with the decrease in Col4 expression level. On the other hand, STAT3
activation and cell proliferation were not influenced by Smad1 deletion in the
NTN model. Therefore, we investigated another factor that activates cell
proliferation in the absence of Smad1. Id2 induced VEGF secretion and subsequent
STAT3 activation, independently of Smad1 expression in mouse mesangial cells.
Here we show that Smad1 plays an important role in the development of glomerular
injury without affecting cell proliferation, in progressive glomerulonephritis.
PMID- 27492140
TI - Azithromycin as an adjunct to non-surgical periodontal therapy: a systematic
review.
AB - The aim of this study was to investigate the current published work relating to
the clinical benefits of the use of systemic azithromycin as an adjunct to non
surgical periodontal therapy. A published work search of PubMed, EMBASE and
Cochrane Register of Controlled Trials up to 27 April 2016 was undertaken. The
large degree of heterogeneity in the types of studies, treatment protocols, test
subjects, sample size and exclusion criteria indicated that the use of narrative
synthesis of all relevant studies was a valid method of review. Of the 194
eligible studies, 15 were found to be of relevance. The majority of studies
demonstrated an additional clinical benefit when azithromycin is used as an
adjunct to non-surgical periodontal therapy, particularly in deeper pockets (>=6
mm). In conclusion, the current body of research on the adjunctive use of
systemic azithromycin in non-surgical periodontal therapy suggests there is a
clinical benefit and that this benefit is greatest in deeper initial pockets (>=6
mm). The findings also suggest that future studies need to be more careful in
subject selection to identify susceptible patients or at risk sites, both the
immunoregulatory effects and antibiotic resistance of azithromycin needs to be
reported, and that study populations need to be more homogeneous.
PMID- 27492142
TI - Chronic hepatitis C virus (HCV) burden in Rhode Island: modelling treatment scale
up and elimination.
AB - We utilized a disease progression model to predict the number of viraemic
infections, cirrhotic cases, and liver-related deaths in the state of Rhode
Island (RI) under four treatment scenarios: (1) current HCV treatment paradigm
(about 215 patients treated annually, Medicaid reimbursement criteria fibrosis
stage ?F3); (2) immediate scale-up of treatment (to 430 annually) and less
restrictive Medicaid reimbursement criteria (fibrosis stage ?F2); (3) immediate
treatment scale-up and no fibrosis stage-specific Medicaid reimbursement criteria
(?F0); (4) an 'elimination' scenario (i.e. a continued treatment scale-up needed
to achieve >90% reduction in viraemic cases by 2030). Under current treatment
models, the number of cirrhotic cases and liver-related deaths will plateau and
peak by 2030, respectively. Treatment scale-up with ?F2 and ?F0 fibrosis stage
treatment criteria could reduce the number of cirrhotic cases by 21.7% and 10.0%,
and the number of liver-related deaths by 19.3% and 7.4%, respectively by 2030.
To achieve a >90% reduction in viraemic cases by 2030, over 2000 persons will
need to be treated annually by 2020. This strategy could reduce cirrhosis cases
and liver-related deaths by 78.9% and 72.4%, respectively by 2030. Increased HCV
treatment uptake is needed to substantially reduce the burden of HCV by 2030 in
Rhode Island.
PMID- 27492141
TI - Preparedness for use of the rapid result HIV self-test by gay men and other men
who have sex with men (MSM): a mixed methods exploratory study among MSM and
those involved in HIV prevention and care.
AB - OBJECTIVES: The aim of the study was to explore preparedness for the HIV self
test among men who have sex with men (MSM) and those involved in HIV prevention
and care. METHODS: A mixed methods exploratory research design was employed,
detailing awareness and willingness to use the self-test and the perceived
barriers and facilitators to implementation. Quantitative and qualitative data
collection and analysis were completed in parallel. Descriptive and inferential
analysis of cross-sectional bar-based survey data collected from MSM through a
self-completed questionnaire and oral fluid specimen collection (n = 999) was
combined with qualitative, thematic, analysis of data collected through 12 expert
focus groups (n = 55) consisting of gay men, National Health Service (NHS) staff,
community organizations, entrepreneurs and activists. Findings were subsequently
combined and assessed for synergies. RESULTS: Among MSM, self-test awareness was
moderate (55%). Greater awareness was associated with increased educational
attainment [adjusted odds ratio 1.51; 95% confidence interval (CI) 1.00-2.30; P =
0.05] and previous history of sexually transmitted infection (STI) testing
(adjusted odds ratio 1.63; 95% CI 1.11-2.39; P = 0.01). Willingness to use the
test was high (89%) and associated with meeting sexual partners online
(unadjusted odds ratio 1.96; 95% CI 1.31-2.94; P < 0.001). Experts highlighted
the overall acceptability of self-testing; it was understood as convenient,
discreet, accessible, and with a low burden to services. However, some
ambivalence towards self-testing was reported; it could reduce opportunities to
engage with wider services, wider health issues and the determinants of risk.
CONCLUSIONS: Self-testing represents an opportunity to reduce barriers to HIV
testing and enhance prevention and access to care. Levels of awareness are
moderate but willingness to use is high. Self-testing may amplify health
inequalities.
PMID- 27492143
TI - Quantitative proteomic analysis exploring progression of colorectal cancer:
Modulation of the serpin family.
AB - Colorectal cancer (CRC) remains a major cause of cancer related-death in
developed countries. The mortality risk is correlated with the stage of CRC
determined at the primary diagnosis and early diagnosis is associated with
enhanced survival rate. Currently, only faecal occult blood tests are used to
screen for CRC. Consequently, there is an incentive to identify specific markers
of CRC. We used quantitative proteomic analysis of serum samples to characterize
protein profiles in adenoma, CRC and healthy control samples. We identified 89
distinct proteins modulated between normal, colorectal adenoma and carcinoma
patients. This list emphasizes proteins involved in enzyme regulator activities
and in particular the serpin family. In serum samples, protein profiles of three
members of the serpin family (SERPINA1, SERPINA3 and SERPINC1) were confirmed by
ELISA assays. We obtained sensitivity/specificity values of 95%/95% for both
SERPINA1 and SERPINC1, and 95%/55% for SERPINA3. This study supports the idea
that serum proteins can discriminate adenoma and CRC patients from unaffected
patients and reveals a panel of regulated proteins that might be useful for
selecting patients for colonoscopy. By evaluating SERPINA1, SERPINA3 and
SERPINC1, we highlight the potential role of the serpin family during the
development and progression of CRC. SIGNIFICANCE: Colorectal cancer (CRC) remains
a major cause of cancer mortality throughout the world. However, very few CRC
biomarkers have satisfactory sensitivity and specificity in clinical practice. To
the best of our knowledge our study is the first to profile sera proteomes
between adenoma, CRC and healthy patients. We report a comprehensive list of
proteins that may be used as early diagnostic biomarkers of CRC. It is noteworthy
that 17% of these modulated proteins have been previously described as candidate
biomarkers in CRC. Enzyme regulator activity was found to be the main molecular
function among these proteins and, in particular, there was an enrichment of
members of the serpin family. The subsequent verification on a new cohort by
ELISA demonstrates that these serpins could be useful to discriminate healthy
from colorectal carcinoma patients with a high sensitivity and specificity. The
combination of these biomarkers should increase predictive powers of CRC
diagnosis. The remaining candidates form a reserve for further evaluation of
additional biomarkers for CRC diagnosis.
PMID- 27492144
TI - MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33
signaling in experimental models of allergic airway inflammation.
AB - BACKGROUND: Allergic airway inflammation is triggered by allergen exposure
through several steps including release of IL-33, which promotes cytokine (IL-5,
IL-13) production by type 2 innate lymphoid cells (ILC2s). MicroRNA (miR)-155 has
recently been described to regulate adaptive responses in allergic inflammation.
However, the role of miR-155 in the regulation of ILC2s remains unexplored.
OBJECTIVE: We sought to elucidate the contribution of miR-155 in ILC2 expansion
using experimental murine models of allergic airway inflammation. METHODS: To
determine the role of miR-155 in the regulation of ILC2s in allergic airway
inflammation, miR-155 deficient (miR-155-/-) and wild-type (WT) mice were
subjected to acute or chronic allergen-induced inflammation or treated with
recombinant IL-33. RESULTS: miR-155 was 10-fold upregulated in WT-derived ILC2s
in response to IL-33. Furthermore, miR-155-/- mice demonstrated impaired lung IL
33 levels in response to allergen challenge and the number of ILC2s was
significantly reduced in allergen-challenged miR-155-/- mice compared with WT
mice. Exogenous IL-33 treatment revealed that miR-155 is needed for IL-33-induced
ILC2 expansion and eosinophilic airway inflammation. Indeed, ILC2s from IL-33
challenged miR-155-/- lungs exhibited impaired proliferation, GATA-3 expression,
and IL-13 production as compared with IL-33-challenged WT ILC2s. CONCLUSIONS: Our
findings for the first time demonstrate that ILC2s and IL-33 signaling are
regulated by miR-155 in allergic airway inflammation.
PMID- 27492145
TI - To compare growth outcomes and cost-effectiveness of "Kangaroo ward care" with
"intermediate intensive care" in stable extremely low birth weight infants:
randomized control trial.
AB - AIMS: To compare growth outcome and cost-effectiveness of "Kangaroo ward care"
(KWC) with "Intermediate intensive care" (IIC) in stable extremely low birth
weight (ELBW) infants. MATERIALS AND METHODS: This is secondary analysis of the
study and we analyzed 62 ELBW infants, 33 were randomized to KWC and 29 to IIC
once the infant reached a weight of 1150 g. Infants in the KWC group were shifted
to the Kangaroo ward immediately after randomization and in the IIC group
received IIC care till they attain a weight of 1250 g before shifting to Kangaroo
ward. RESULTS: The gain in weight (g/day), length (cm/week), and head
circumference (cm/week) were comparable between the two groups. The mean weight,
length, and head circumference were comparable at term gestational age. The
infants in KWC group were shifted five days earlier to Kangaroo ward when
compared to IIC group. The cost-effective analysis using "top-down" and "bottom
up" accounting method showed that there was significant reduction of hospital and
parents expenditure in KWC group (p < 0.001) with approximate saving of 452 USD
for each patient in the KWC group. CONCLUSION: Early shifting of ELBW infants for
KWC is very efficacious and cost-effective intervention when compared to IIC.
(CTRI/2014/05/004625).
PMID- 27492146
TI - Central Venous Occlusion in the Hemodialysis Patient.
AB - Central venous stenosis (CVS) is encountered frequently among hemodialysis
patients. Prior ipsilateral central venous catheterization and cardiac rhythm
device insertions are common risk factors, but CVS can also occur in the absence
of this history. Chronic CVS can cause thrombosis with partial or complete
occlusion of the central vein at the site of stenosis. CVS is frequently
asymptomatic and identified as an incidental finding during imaging studies.
Symptomatic CVS presents most commonly as an upper- or lower-extremity edema
ipsilateral to the CVS. Previously unsuspected CVS may become symptomatic after
placement of an ipsilateral vascular access. The likelihood of symptomatic CVS
may be affected by the central venous catheter (CVC) location; CVC side; duration
of CVC dependence; type, location, and blood flow of the ipsilateral access; and
extent of collateral veins. Venous angiography is the gold standard for
diagnosis. Percutaneous transluminal angioplasty and stent placement can improve
the stenosis and alleviate symptoms, but CVS typically recurs frequently,
requiring repeated interventions. Refractory symptomatic CVS may require ligation
of the ipsilateral vascular access. Because no available treatment option is
curative, the goal should be to prevent CVS by minimizing catheters and central
vein instrumentation in patients with chronic kidney disease and dialysis
patients.
PMID- 27492147
TI - Risk factors for coronary artery disease and acute coronary syndrome in patients
<=40 years old.
AB - OBJECTIVE: In this study, we assessed the risk factor profile in premature
coronary artery disease (CAD) and acute coronary syndrome for adults <=40 years
old. METHODS: A retrospective chart analysis of 397 patients <=40 years old
admitted from 2005 to 2014 for chest pain and who underwent coronary
arteriography. RESULTS: Of 397 patients that had undergone coronary
arteriography, 54% had CAD while 46% had normal coronary arteries. When compared
with patients with normal coronary arteries, patients with CAD were more likely
to smoke tobacco, have dyslipidemia, be diabetic, have BMI >30 kg/m(2), have a
family history of premature CAD and be male in gender. CONCLUSION: Healthcare
intervention in the general population through screening, counseling and
education regarding the risk factors is warranted to reduce premature CAD.
PMID- 27492148
TI - PKM2 enhances chemosensitivity to cisplatin through interaction with the mTOR
pathway in cervical cancer.
AB - Pyruvate kinase M2 (PKM2) is a key driver of aerobic glycolysis in cancer cells
and has been shown to be up-regulated by mTOR in vitro. Our previous proteomic
profiling studies showed that PKM2 was significantly upregulated in cervical
cancer tissues after treatment with neoadjuvant chemotherapy (NACT). Whether PKM2
expression predicts cisplatin-based NACT sensitivity and is mTOR dependent in
cervical cancer patients remains unclear. Using paired tumor samples (pre- and
post-chemotherapy) from 36 cervical cancer patients, we examined mTOR, HIF
1alpha, c-Myc, and PKM2 expression in cervical cancer samples and investigated
the response to cisplatin-based NACT. In addition, we established PKM2 suppressed
cervical cancer cell lines and evaluated their sensitivity to cisplatin in vitro.
We found that the mTOR/HIF-1alpha/c-Myc/PKM2 signaling pathway was significantly
downregulated in post-chemotherapy cervical cancer tissues. High levels of mTOR,
HIF-1alpha, c-Myc, and PKM2 were associated with a positive chemotherapy response
in cervical cancer patients treated with cisplatin-based NACT. In vitro, PKM2
knockdown desensitized cervical cancer cells to cisplatin. Moreover, PKM2 had
complex interactions with mTOR pathways. mTOR, HIF1alpha, c-Myc, and PKM2
expression in cervical cancer may serve as predictive biomarkers to cisplatin
based chemotherapy. PKM2 enhances chemosensitivity to cisplatin through
interaction with the mTOR pathway in cervical cancer.
PMID- 27492150
TI - Case report: progressive multifocal encephalopathy (PML) causing an isolated
cerebellar syndrome.
PMID- 27492149
TI - Characteristics of European adults who dropped out from the Food4Me Internet
based personalised nutrition intervention.
AB - OBJECTIVE: To characterise participants who dropped out of the Food4Me Proof-of
Principle study. DESIGN: The Food4Me study was an Internet-based, 6-month, four
arm, randomised controlled trial. The control group received generalised dietary
and lifestyle recommendations, whereas participants randomised to three different
levels of personalised nutrition (PN) received advice based on dietary,
phenotypic and/or genotypic data, respectively (with either more or less frequent
feedback). SETTING: Seven recruitment sites: UK, Ireland, The Netherlands,
Germany, Spain, Poland and Greece. SUBJECTS: Adults aged 18-79 years (n 1607).
RESULTS: A total of 337 (21 %) participants dropped out during the intervention.
At baseline, dropouts had higher BMI (0.5 kg/m2; P<0.001). Attrition did not
differ significantly between individuals receiving generalised dietary guidelines
(Control) and those randomised to PN. Participants were more likely to drop out
(OR; 95 % CI) if they received more frequent feedback (1.81; 1.36, 2.41;
P<0.001), were female (1.38; 1.06, 1.78; P=0.015), less than 45 years old (2.57;
1.95, 3.39; P<0.001) and obese (2.25; 1.47, 3.43; P<0.001). Attrition was more
likely in participants who reported an interest in losing weight (1.53; 1.19,
1.97; P<0.001) or skipping meals (1.75; 1.16, 2.65; P=0.008), and less likely if
participants claimed to eat healthily frequently (0.62; 0.45, 0.86; P=0.003).
CONCLUSIONS: Attrition did not differ between participants receiving generalised
or PN advice but more frequent feedback was related to attrition for those
randomised to PN interventions. Better strategies are required to minimise
dropouts among younger and obese individuals participating in PN interventions
and more frequent feedback may be an unnecessary burden.
PMID- 27492151
TI - [Cases and duration of mechanical ventilation in German hospitals : An analysis
of DRG incentives and developments in respiratory medicine].
AB - BACKGROUND: Diagnosis-related groups (DRGs) have been used to reimburse hospitals
services in Germany since 2003/04. Like any other reimbursement system, DRGs
offer specific incentives for hospitals that may lead to unintended consequences
for patients. In the German context, specific procedures and their documentation
are suspected to be primarily performed to increase hospital revenues. Mechanical
ventilation of patients and particularly the duration of ventilation, which is an
important variable for the DRG-classification, are often discussed to be among
these procedures. OBJECTIVES: The aim of this study was to examine incentives
created by the German DRG-based payment system with regard to mechanical
ventilation and to identify factors that explain the considerable increase of
mechanically ventilated patients in recent years. Moreover, the assumption that
hospitals perform mechanical ventilation in order to gain economic benefits was
examined. MATERIAL AND METHODS: In order to gain insights on the development of
the number of mechanically ventilated patients, patient-level data provided by
the German Federal Statistical Office and the German Institute for the Hospital
Remuneration System were analyzed. The type of performed ventilation, the total
number of ventilation hours, the age distribution, mortality and the DRG
distribution for mechanical ventilation were calculated, using methods of
descriptive and inferential statistics. Furthermore, changes in DRG-definitions
and changes in respiratory medicine were compared for the years 2005-2012.
RESULTS: Since the introduction of the DRG-based payment system in Germany, the
hours of ventilation and the number of mechanically ventilated patients have
substantially increased, while mortality has decreased. During the same period
there has been a switch to less invasive ventilation methods. The age
distribution has shifted to higher age-groups. A ventilation duration determined
by DRG definitions could not be found. CONCLUSION: Due to advances in respiratory
medicine, new ventilation methods have been introduced that are less prone to
complications. This development has simultaneously improved survival rates. There
was no evidence supporting the assumption that the duration of mechanical
ventilation is influenced by the time intervals relevant for DRG grouping.
However, presumably operational routines such as staff availability within early
and late shifts of the hospital have a significant impact on the termination of
mechanical ventilation.
PMID- 27492152
TI - Serious engagement in sport and health benefits among Korean immigrants in the
USA.
AB - There is a dearth of information pertaining to ethnicity and serious leisure
among immigrants. The purpose of our study was to explore the health benefits of
serious engagement in sports among Korean immigrants who are part of club
activities. Using semi-structured in-depth interviews, we identified three themes
associated with the benefits of serious leisure: (a) coping with acculturative
stress, (b) creating ethnic strength, and (c) personal benefits. Participants
gain personal and social benefits by pursuing leisure activities in a serious
manner within their ethnic in-group.
PMID- 27492153
TI - Ommaya reservoir in the treatment of cryptococcal meningitis.
AB - The objective is to study the role of Ommaya reservoir in the treatment of
cryptococcal meningitis. The clinical data of 42 patients with cryptococcal
meningitis were retrospectively studied. The Ommaya group included 20 patients,
who were treated with Amphotericin B (Am B) and Ommaya reservoir implantation.
The non-Ommaya group contained 22 patients, who were just treated with
Amphotericin B (Am B). In the Ommaya group (surgical group), all 20 patients with
Ommaya reservoir were fully recovered, and their average hospital stay period and
average treatment period with Amphotericin B were 105.3 +/- 18.3 and 75.0 +/-
18.1 days, respectively. In the non-Ommaya group (control group), 16 patients
were fully recovered and the average hospital stay period and average treatment
period with Amphotericin B of these 22 patients were 139.6 +/- 29.5 and 150.0 +/-
32.2 days, respectively. In the surgical group, average period of cryptococcus
disappearance was 20 +/- 8 days, while in the control group, that was 35 +/- 10
days. The clinical efficacy was better in surgical group than control group (P <
0.05). Ommaya reservoir implantation is a valuable approach in the treatment of
cryptococcal meningitis and can improve the cure rate, decrease mortality, and
shorten the period of treatment.
PMID- 27492154
TI - Acta Neurologica Belgica: a youthful centenarian.
PMID- 27492156
TI - Mental illness research in the Gulf Cooperation Council: a scoping review.
AB - Rapid growth and development in recent decades has seen mental health and mental
illness emerge as priority health concerns for the Gulf Cooperation Council
(Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates). As a
result, mental health services in the region are being redefined and expanded.
However, there is a paucity of local research to guide ongoing service
development. Local research is important because service users' experience of
mental illness and mental health services are linked to their sociocultural
context. In order for service development to be most effective, there is a need
for increased understanding of the people who use these services.This article
aims to review and synthesize mental health research from the Gulf Cooperation
Council. It also seeks to identify gaps in the literature and suggest directions
for future research. A scoping framework was used to conduct this review. To
identify studies, database searches were undertaken, regional journals were hand
searched, and reference lists of included articles were examined. Empirical
studies undertaken in the Gulf Cooperation Council that reported mental health
service users' experience of mental illness were included. Framework analysis was
used to synthesize results. Fifty-five studies met inclusion criteria and the
following themes were identified: service preferences, illness (symptomology,
perceived cause, impact), and recovery (traditional healing, family support,
religion). Gaps included contradictory findings related to the supportive role of
the Arabic extended family and religion, under-representation of women in study
samples, and limited attention on illness management outside of the hospital
setting.From this review, it is clear that the sociocultural context in the
region is linked to service users' experience of mental illness. Future research
that aims to fill the identified gaps and develop and test culturally appropriate
interventions will aid practice and policy development in the region.
PMID- 27492157
TI - Blended learning: how can we optimise undergraduate student engagement?
AB - BACKGROUND: Blended learning is a combination of online and face-to-face learning
and is increasingly of interest for use in undergraduate medical education. It
has been used to teach clinical post-graduate students pharmacology but needs
evaluation for its use in teaching pharmacology to undergraduate medical
students, which represent a different group of students with different learning
needs. METHODS: An existing BSc-level module on neuropharmacology was redesigned
using the Blended Learning Design Tool (BLEnDT), a tool which uses learning
domains (psychomotor, cognitive and affective) to classify learning outcomes into
those taught best by self-directed learning (online) or by collaborative learning
(face-to-face). Two online courses were developed, one on Neurotransmitters and
the other on Neurodegenerative Conditions. These were supported with face-to-face
tutorials. Undergraduate students' engagement with blended learning was explored
by the means of three focus groups, the data from which were analysed
thematically. RESULTS: Five major themes emerged from the data 1) Purpose and
Acceptability 2) Structure, Focus and Consolidation 3) Preparation and workload
4) Engagement with e-learning component 5) Future Medical Education. CONCLUSION:
Blended learning was acceptable and of interest to undergraduate students
learning this subject. They expressed a desire for more blended learning in their
courses, but only if it was highly structured, of high quality and supported by
tutorials. Students identified that the 'blend' was beneficial rather than purely
online learning.
PMID- 27492155
TI - Gender differences and gender convergence in alcohol use over the past three
decades (1984-2008), The HUNT Study, Norway.
AB - BACKGROUND: To examine changes in men's and women's drinking in Norway over a 20
year period, in order to learn whether such changes have led to gender
convergence in alcohol drinking. METHODS: Repeated cross-sectional studies (in
1984-86, 1995-97, and 2006-08) of a large general population living in a
geographically defined area (county) in Norway. Information about alcohol
drinking is based on self-report questionnaires. Not all measures were assessed
in all three surveys. RESULTS: Adult alcohol drinking patterns have changed
markedly over a 20-year period. Abstaining has become rarer while consumption and
rates of recent drinking and problematic drinking have increased. Most changes
were in the same direction for men and women, but women have moved towards men's
drinking patterns in abstaining, recent drinking, problematic drinking and
consumption. Intoxication (among recent drinkers) has decreased in both genders,
but more in men than in women. The declines in gender differences, however, were
age-specific and varied depending on which drinking behavior and which beverage
was taken into account. CONCLUSIONS: There has been a gender convergence in most
drinking behaviours, including lifetime history of problem drinking, over the
past 2-3 decades in this Norwegian general population, but the reasons for this
convergence appear to be complex.
PMID- 27492158
TI - Doctors' reports about palliative systemic treatment: A medical record study.
AB - BACKGROUND: Decisions about palliative systemic treatment are key elements of
palliative and end-of-life care. Such decisions must often be made in complex,
clinical situations. AIM: To explore the content of medical records of patients
with advanced non-small cell lung cancer and pancreatic cancer with specific
emphasis on doctors' notes about decisions on palliative systemic treatment.
DESIGN: Medical record review (2009-2012) of 147 cancer patients containing 276
notes about palliative systemic treatment. We described the proportion of
notes/medical records containing pre-specified items relevant to palliative
systemic treatment. We selected patients using the nationwide Netherlands Cancer
Registry. SETTING: Hospital based. RESULTS: About 75% of all notes reported
doctors' considerations to start/continue palliative systemic treatment,
including information about the prognosis (47%), possible survival gain (22%),
patients' wish for palliative systemic treatment (33%), impact on quality of life
(8%), and patient's age (3%). Comorbidity (82%), smoking status (78%) and
drinking behaviour (63%) were more often documented than patients' performance
status (16%). Conversations with the patient/family about palliative systemic
treatment were reported in 49% of all notes. Response measurements and dose
adaptations were documented in 75% and 71% of patients who received palliative
systemic treatment respectively. CONCLUSION: Medical records provide insight into
the decision-making process about palliative systemic treatment. The content and
detail of doctors' notes, however, widely varies especially concerning their
palliative systemic treatment considerations. Registries that aim to measure the
quality of (end-of-life) care must be aware of this outcome. Future research
should further explore how medical records can best assist in evaluating the
quality of the decision-making process in the patient's final stage of life.
PMID- 27492159
TI - What is the evidence for conducting palliative care family meetings? A systematic
review.
AB - BACKGROUND: Structured family meeting procedures and guidelines suggest that
these forums enhance family-patient-team communication in the palliative care
inpatient setting. However, the vulnerability of palliative patients and the
resources required to implement family meetings in accordance with recommended
guidelines make better understanding about the effectiveness of this type of
intervention an important priority. Aim and design: This systematic review
examines the evidence supporting family meetings as a strategy to address the
needs of palliative patients and their families. The review conforms to the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement.
DATA SOURCES: Six medical and psychosocial databases and "CareSearch," a
palliative care-specific database, were used to identify studies reporting
empirical data, published in English in peer-reviewed journals from 1980 to March
2015. Book chapters, expert opinion, and gray literature were excluded. The
Cochrane Collaboration Tool assessed risk of bias. RESULTS: Of the 5051 articles
identified, 13 met the inclusion criteria: 10 quantitative and 3 qualitative
studies. There was low-level evidence to support family meetings. Only two
quantitative pre- and post-studies used a validated palliative care family
outcome measure with both studies reporting significant results post-family
meetings. Four other quantitative studies reported significant results using non
validated measures. CONCLUSION: Despite the existence of consensus-based family
meeting guidelines, there is a paucity of evidence to support family meetings in
the inpatient palliative care setting. Further research using more robust
designs, validated outcome measures, and an economic analysis are required to
build the family meeting evidence before they are routinely adopted into clinical
practice.
PMID- 27492160
TI - Current status of accurate prognostic awareness in advanced/terminally ill cancer
patients: Systematic review and meta-regression analysis.
AB - BACKGROUND: No systematic meta-analysis is available on the prevalence of cancer
patients' accurate prognostic awareness and differences in accurate prognostic
awareness by publication year, region, assessment method, and service received.
AIM: To examine the prevalence of advanced/terminal cancer patients' accurate
prognostic awareness and differences in accurate prognostic awareness by
publication year, region, assessment method, and service received. DESIGN:
Systematic review and meta-analysis. METHODS: MEDLINE, Embase, The Cochrane
Library, CINAHL, and PsycINFO were systematically searched on accurate prognostic
awareness in adult patients with advanced/terminal cancer (1990-2014). Pooled
prevalences were calculated for accurate prognostic awareness by a random-effects
model. Differences in weighted estimates of accurate prognostic awareness were
compared by meta-regression. RESULTS: In total, 34 articles were retrieved for
systematic review and meta-analysis. At best, only about half of
advanced/terminal cancer patients accurately understood their prognosis (49.1%;
95% confidence interval: 42.7%-55.5%; range: 5.4%-85.7%). Accurate prognostic
awareness was independent of service received and publication year, but highest
in Australia, followed by East Asia, North America, and southern Europe and the
United Kingdom (67.7%, 60.7%, 52.8%, and 36.0%, respectively; p = 0.019).
Accurate prognostic awareness was higher by clinician assessment than by patient
report (63.2% vs 44.5%, p < 0.001). CONCLUSION: Less than half of
advanced/terminal cancer patients accurately understood their prognosis, with
significant variations by region and assessment method. Healthcare professionals
should thoroughly assess advanced/terminal cancer patients' preferences for
prognostic information and engage them in prognostic discussion early in the
cancer trajectory, thus facilitating their accurate prognostic awareness and the
quality of end-of-life care decision-making.
PMID- 27492161
TI - Eccentric Contraction-Induced Muscle Injury: Reproducible, Quantitative,
Physiological Models to Impair Skeletal Muscle's Capacity to Generate Force.
AB - In order to investigate the molecular and cellular mechanisms of muscle
regeneration an experimental injury model is required. Advantages of eccentric
contraction-induced injury are that it is a controllable, reproducible, and
physiologically relevant model to cause muscle injury, with injury being defined
as a loss of force generating capacity. While eccentric contractions can be
incorporated into conscious animal study designs such as downhill treadmill
running, electrophysiological approaches to elicit eccentric contractions and
examine muscle contractility, for example before and after the injurious
eccentric contractions, allows researchers to circumvent common issues in
determining muscle function in a conscious animal (e.g., unwillingness to
participate). Herein, we describe in vitro and in vivo methods that are reliable,
repeatable, and truly maximal because the muscle contractions are evoked in a
controlled, quantifiable manner independent of subject motivation. Both methods
can be used to initiate eccentric contraction-induced injury and are suitable for
monitoring functional muscle regeneration hours to days to weeks post-injury.
PMID- 27492162
TI - Volumetric Muscle Loss.
AB - Volumetric muscle loss (VML) injury is prevalent in severe extremity trauma and
is an emerging focus area among orthopedic and regenerative medicine fields. VML
injuries are the result of an abrupt, frank loss of tissue and therefore of
different etiology from other standard rodent injury models to include eccentric
contraction, ischemia reperfusion, crush, and freeze injury. The current focus of
many VML-related research efforts is to regenerate the lost muscle tissue and
thereby improve muscle strength. Herein, we describe a VML model in the anterior
compartment of the hindlimb that is permissible to repeated neuromuscular
strength assessments and is validated in mouse, rat, and pig.
PMID- 27492163
TI - Freeze Injury of the Tibialis Anterior Muscle.
AB - Freeze injury is physically induced by exposing skeletal muscle to an extremely
cold probe, and results in a robust degenerative and inflammatory response. One
unique aspect of freeze injury is that it destroys not only the muscle fiber
cells, but also all of the mononuclear cells in the zone of injury. Repair of the
muscle is accomplished by satellite cells from outside of the zone of injury,
which must migrate in and which may interact with inflammatory cells, hence the
length of time before apparent histological recovery of the most damaged zone is
typically somewhat longer with freeze injury than with other physical or chemical
methods of injury. In this chapter, we present a detailed protocol for the freeze
injury of the tibialis anterior (TA) muscle in mouse.
PMID- 27492164
TI - Synergist Ablation as a Rodent Model to Study Satellite Cell Dynamics in Adult
Skeletal Muscle.
AB - In adult skeletal muscles, satellite cells are the primary myogenic stem cells
involved in myogenesis. Normally, they remain in a quiescent state until
activated by a stimulus, after which they proliferate, differentiate, and fuse
into an existing myofiber or form a de novo myofiber. To study satellite cell
dynamics in adult murine models, most studies utilize regeneration models in
which the muscle is severely damaged and requires the participation from
satellite cells in order to repair. Here, we describe a model to study satellite
cell behavior in muscle hypertrophy that is independent of muscle
regeneration.Synergist ablation surgery involves the surgical removal of the
gastrocnemius and soleus muscles resulting in functional overload of the
remaining plantaris muscle. This functional overload results in myofiber
hypertrophy, as well as the activation, proliferation, and fusion of satellite
cells into the myofibers. Within 2 weeks of functional overload, satellite cell
content increases approximately 275 %, an increase that is accompanied with a ~60
% increase in the number of myonuclei. Therefore, this can be used as an
alternative model to study satellite cell behavior in adulthood that is different
from regeneration, and capable of revealing new satellite cell functions in
regulating muscle adaptation.
PMID- 27492165
TI - Inducing and Evaluating Skeletal Muscle Injury by Notexin and Barium Chloride.
AB - Models of skeletal muscle injury in animal models are invaluable tools to assess
muscle stem cell (MuSC)-mediated tissue repair. The optimization and
comprehensive evaluation of these approaches have greatly improved our ability to
assess MuSC regenerative potential. Here we describe the procedures for skeletal
muscle injury with notexin and BaCl2 and assessment of the dynamics of tissue
regeneration.
PMID- 27492167
TI - Fibrosis-Inducing Strategies in Regenerating Dystrophic and Normal Skeletal
Muscle.
AB - The excessive accumulation of collagens (fibrosis) impairs the function of vital
tissues and organs. Fibrosis is a hallmark of severe muscular dystrophies, such
as the incurable Duchenne Muscular Dystrophy (DMD), where skeletal muscle is
substituted by scar (fibrotic) tissue as disease advances. One of the major
obstacles in increasing our ability to combat fibrosis-driven muscular dystrophy
progression is that no optimal in vivo models of muscle fibrosis are currently
available, limiting fibrosis research and the development of novel therapies. In
this chapter we describe different experimental strategies to accelerate and
enhance muscle fibrosis in vivo in the widely used animal model for DMD, the mdx
mouse. Since excessive tissue scarring also hampers the normal regeneration
process after muscle injury, we have extended these fibrogenic strategies to the
muscle of normal (non-diseased) mice. These strategies will allow fibrosis
induction and assessment in a wide array of genetically modified mouse lines in
physiological and pathological conditions of muscle regeneration. They should
eventually improve our ability to combat fibrosis and foster muscle regeneration
in DMD.
PMID- 27492166
TI - Cardiotoxin Induced Injury and Skeletal Muscle Regeneration.
AB - Skeletal muscles have a tremendous capacity for repair and regeneration in
response to injury. This capacity for regeneration is largely due to a myogenic
stem cell population, termed satellite cells, which are resident in adult
skeletal muscles. In order to decipher the mechanisms that govern myogenic stem
cell quiescence, activation, differentiation, and self-renewal, a reproducible
injury model is required. Therefore, we have utilized the delivery of the
myonecrotic agent, cardiotoxin, to examine the molecular mechanisms of myogenic
stem cells in response to injury. Here, we describe our experience using
cardiotoxin as a potent myonecrotic agent to study skeletal muscle regeneration.
We provide a detailed protocol to examine skeletal muscle injury and regeneration
using morphological analyses.
PMID- 27492168
TI - Isolation, Cryosection and Immunostaining of Skeletal Muscle.
AB - Adult skeletal muscle is maintained and repaired by resident stem cells called
satellite cells, located between the plasmalemma of a muscle fiber, and the
surrounding basal lamina. When needed, satellite cells are activated to form
proliferative myoblasts, that then differentiate and fuse to existing muscle
fibers, or fuse together to form replacement myofibers. In parallel, a proportion
of satellite cells self-renew, to maintain the stem cell pool. To date, Pax7 is
the marker of choice for identifying quiescent satellite cells. Co-immunostaining
of skeletal muscle with Pax7 and laminin allows both identification of satellite
cells, and the myofiber that they are associated with. Furthermore, satellite
cells can be followed through the early stages of the myogenic program by co
immunostaining with myogenic regulatory factors such as MyoD. To test genetically
modified mice for satellite cell expression, co-immunostaining can be performed
for Pax7 and reporter genes such as eGFP. Here, we describe a method for
identification of satellite cells in skeletal muscle sections, including muscle
isolation, cryosectioning and co-immunostaining for Pax7 and laminin.
PMID- 27492169
TI - Isolation of Mouse Periocular Tissue for Histological and Immunostaining Analyses
of the Extraocular Muscles and Their Satellite Cells.
AB - The extraocular muscles (EOMs) comprise a group of highly specialized skeletal
muscles controlling eye movements. Although a number of unique features of EOMs
including their sparing in Duchenne muscular dystrophy have drawn a continuous
interest, knowledge about these hard to reach muscles is still limited. The goal
of this chapter is to provide detailed methods for the isolation and histological
analysis of mouse EOMs. We first introduce in brief the basic anatomy and
established nomenclature of the extraocular primary and accessory muscles. We
then provide a detailed description with step-by-step images of our procedure for
isolating (and subsequently cryosectioning) EOMs while preserving the integrity
of their original structural organization. Next, we present several useful
histological protocols frequently used by us, including: (1) a method for
highlighting the general organization of periocular tissue, using the MyoD(Cre) *
R26(mTmG) reporter mouse that elegantly distinguishes muscle (MyoD(Cre)-driven
GFP(+)) from the non-myogenic constituents (Tomato(+)); (2) analysis by H&E
staining, allowing for example, detection of the pathological features of the
dystrophin-null phenotype in affected limb and diaphragm muscles that are absent
in EOMs; (3) detection of the myogenic progenitors (i.e., satellite cells) in
their native position underneath the myofiber basal lamina using Pax7/laminin
double immunostaining. The EOM tissue harvesting procedure described here can
also be adapted for isolating and studying satellite cells and other cell types.
Overall, the methods described in this chapter should provide investigators the
necessary tools for entering the EOM research field and contribute to a better
understanding of this highly specialized muscle group and its complex micro
anatomy.
PMID- 27492170
TI - Skeletal Muscle Tissue Clearing for LacZ and Fluorescent Reporters, and
Immunofluorescence Staining.
AB - Skeletal muscle is a highly ordered yet complex tissue containing several cell
types that interact with each other in order to maintain structure and
homeostasis. It is also a highly regenerative tissue that responds to damage in a
highly intricate but stereotypic manner, with distinct spatial and temporal
kinetics. Proper examination of this process requires one to look at the three
dimensional orientation of the cellular and subcellular components, which can be
accomplished through tissue clearing. While there has been a recent surge of
protocols to study biology in whole tissue, it has primarily focused on the
nervous system. This chapter describes the workflow for whole mount analysis of
murine skeletal muscle for LacZ reporters, fluorescent reporters and
immunofluorescence staining. Using this technique, we are able to visualize LacZ
reporters more effectively in deep tissue samples, and to perform fluorescent
imaging with a depth greater than 1700 MUm.
PMID- 27492171
TI - Isolation, Culture, Functional Assays, and Immunofluorescence of Myofiber
Associated Satellite Cells.
AB - Adult skeletal muscle stem cells, termed satellite cells, regenerate and repair
the functional contractile cells in adult skeletal muscle called myofibers.
Satellite cells reside in a niche between the basal lamina and sarcolemma of
myofibers. Isolating single myofibers and their associated satellite cells
provides a culture system that partially mimics the in vivo environment. We
describe methods for isolating and culturing intact individual myofibers and
their associated satellite cells from the mouse extensor digitorum longus muscle.
Following dissection and isolation of individual myofibers we provide protocols
for myofiber transplantation, satellite cell transfection, immune detection of
satellite cell antigens, and assays to examine satellite cell self-renewal and
proliferation.
PMID- 27492172
TI - Flow Cytometry and Transplantation-Based Quantitative Assays for Satellite Cell
Self-Renewal and Differentiation.
AB - In response to muscle damage, satellite cells proliferate and undertake both
differentiation and self-renewal, generating new functional muscle tissue and
repopulating this new muscle with stem cells for future injury responses. For
many questions relating to the physiological regulation of satellite cells,
quantitative readouts of self-renewal and differentiation can be very useful.
There is a particular need for a quantitative assay for satellite cell self
renewal that does not rely solely upon sectioning, staining and counting cells in
sections. In this chapter, we provide detailed methods for quantifying the self
renewal and differentiation potential of a given population of satellite cells
using an assay involving transplantation into injured, regenerating muscle
together with specific markers for donor cell identity and state of
differentiation. In particular, using the Pax7-ZsGreen transgene as a marker of
satellite cell state, self-renewal can be quantified by FACS on transplanted
muscle to actually count the total number of resident satellite cells at time
points following transplantation.
PMID- 27492173
TI - Noninvasive Tracking of Quiescent and Activated Muscle Stem Cell (MuSC)
Engraftment Dynamics In Vivo.
AB - Muscle stem cells play a central role in muscle regeneration. Most studies in the
field of muscle regeneration focus on the unraveling of muscle stem cell biology
to devise strategies for treating failing muscles as seen in aging and muscle
related diseases. However, the common method used in assessing stem cell function
in vivo is laborious, as it involves time-consuming immunohistological analyses
by microscopy on serial cryo-sections of the muscle post stem cell
transplantation. Here we describe an alternative method, which adapts the
bioluminescence imaging (BLI) technique to allow noninvasive tracking of
engrafted stem-cell function in vivo in real-time. This assay system enables
longitudinal studies in the same mice over time and reveals parameters, not
feasible by traditional analysis, such as the magnitude and dynamics of engrafted
muscle stem cell expansion in vivo in response to a particular drug treatment or
muscle injury.
PMID- 27492174
TI - Myogenic Progenitors from Mouse Pluripotent Stem Cells for Muscle Regeneration.
AB - Muscle homeostasis is maintained by resident stem cells which, in both pathologic
and non-pathologic conditions, are able to repair or generate new muscle fibers.
Although muscle stem cells have tremendous regenerative potential, their
application in cell therapy protocols is prevented by several restrictions,
including the limited ability to grow ex vivo. Since pluripotent stem cells have
the unique potential to both self-renew and expand almost indefinitely, they have
become an attractive source of progenitors for regenerative medicine studies. Our
lab has demonstrated that embryonic stem cell (ES)-derived myogenic progenitors
retain the ability to repair existing muscle fibers and contribute to the pool of
resident stem cells. Because of their relevance in both cell therapy and disease
modeling, in this chapter we describe the protocol to derive myogenic progenitors
from murine ES cells followed by their intramuscular delivery in a murine
muscular dystrophy model.
PMID- 27492175
TI - Assaying Human Myogenic Progenitor Cell Activity by Reconstitution of Muscle
Fibers and Satellite Cells in Immunodeficient Mice.
AB - Comparing the functional myogenic potential of various human cell populations is
an important step in the preclinical evaluation of cell transplantation as a
means to treat human muscle disease and degeneration. Culture systems allow one
to gage the potential of cell populations to proliferate and undergo myogenic
differentiation under specific conditions. An in vivo assay evaluates the ability
of cells to differentiate and generate muscle fibers within a natural
environment, and importantly, evaluates the potential of donor cells to
reconstitute the satellite cell niche. In this chapter, we describe a technique
for isolating mononuclear cells from human muscle samples, and a method of
xenotransplantation for assessing functional myogenic potential in vivo. Briefly,
cell populations are injected into the pre-irradiated and regenerating muscle of
immunodeficient mice. The injected muscle is frozen at specific time points after
injection and cryosections analyzed by immunostaining. The number of human
dystrophin-expressing fibers and the number of Pax7(+) human lamin A/C(+) nuclei
are determined, which provides a quantitative method of comparing the in vivo
functional potential of cell populations.
PMID- 27492176
TI - Methods for Mitochondria and Mitophagy Flux Analyses in Stem Cells of Resting and
Regenerating Skeletal Muscle.
AB - Mitochondria generate most of the cell's supply of ATP as a source of energy.
They are also implicated in the control of cell's growth and death. Because of
these critical functions, mitochondrial fitness is key for cellular homeostasis.
Often, however, mitochondria become defective following damage or stress. To
prevent accumulation of damaged mitochondria, the cells clear them through
mitophagy, which is defined as the selective degradation of mitochondria by
autophagy (the process for degradation of long-lived proteins and damaged
organelles in lysosomes). Recently, constitutive mitophagic activity has been
reported in quiescent muscle stem cells (satellite cells), which sustain
regeneration of skeletal muscle. In response to muscle damage, these cells
activate, expand, and differentiate to repair damaged myofibers. Mitophagy was
shown to be required for maintenance of satellite cells in their healthy
quiescent state. Conversely, damaged mitochondria accumulated in satellite cells
with aging and this was attributed to defective mitophagy. This caused increased
levels of reactive oxygen species (ROS) and loss of muscle stem cell regenerative
capacity at old age. In this chapter, we describe different experimental
strategies to evaluate mitochondria status and mitophagy in muscle stem cells
from mice. They should improve our ability to study muscle stem homeostasis in
adult life, and their loss of function in aging and disease.
PMID- 27492177
TI - Identification, Isolation, and Characterization of Mesenchymal Progenitors in
Mouse and Human Skeletal Muscle.
AB - Mesenchymal progenitors residing in the muscle interstitial space contribute to
pathogeneses such as fat infiltration and fibrosis. Because fat infiltration and
fibrosis are hallmarks of diseased muscle, it is important to establish an
accurate and reproducible method for isolating mesenchymal progenitors for
research on muscle diseases. In this chapter, we describe methods based on
fluorescence-activated cell sorting (FACS) to purify mesenchymal progenitors from
mouse and human skeletal muscle using the most reliable marker for mesenchymal
progenitors, PDGFRalpha. These methods allow concurrent isolation of the muscle
stem cells called satellite cells. The quality of isolated mesenchymal
progenitors is confirmed by their remarkable adipogenic potential without
myogenic capacity, while purified satellite cells possess robust myogenic
activity with no adipogenic potential. Simultaneous isolation of both mesenchymal
progenitors and satellite cells from mouse and human tissues provides a powerful
platform for studying skeletal muscle regeneration and diseases.
PMID- 27492178
TI - FACS Fractionation and Differentiation of Skeletal-Muscle Resident Multipotent
Tie2+ Progenitors.
AB - The skeletal muscle niche is complex and heterogeneous. Over the past few
decades, various groups have reported the existence of multiple adult stem cell
populations within this environment. Techniques commonly used to identify and
assess the differentiation capacities of these cellular fractions, oftentimes
rare populations, include the use of lineage tracers, immunofluorescence and
histochemistry, flow cytometry, gene expression assays, and phenotypic analysis
in culture or in vivo. In 2012, our lab identified and characterized a skeletal
muscle resident Tie2+ progenitor that exhibits adipogenic, chondrogenic, and
osteogenic differentiation potentials (Wosczyna et al., J Bone Miner Res 27:1004
1017, 2012). This Tie2+ progenitor also expresses the markers PDGFRalpha and Sca
1 which in turn label a population of muscle-resident fibro/adipogenic
progenitors (FAPs) (Joe et al., Nat Cell Biol 12:153-163, 2010; Uezumi et al.,
Nat Cell Biol 12:143-152, 2010), suggesting similar identities or overlap in the
two mesenchymal progenitor populations. Our study demonstrated that these Tie2
expressing mesenchymal progenitors contribute robustly to BMP-induced heterotopic
ossification (HO) in mice, and therefore could represent a key cellular target
for therapeutic intervention in HO treatment (Wosczyna et al., J Bone Miner Res
27:1004-1017, 2012). In this chapter, we provide a detailed description of our
updated fluorescence-activated cell sorting (FACS) strategy and describe cell
culture methods for differentiation of Tie2+ progenitors to adipogenic and
osteogenic fates. This strategy is easily adaptable for the prospective isolation
of other rare subpopulations resident in skeletal muscle.
PMID- 27492179
TI - In Vitro Assays to Determine Skeletal Muscle Physiologic Function.
AB - In vitro muscle contractile function assays are important to characterize the
differences between different muscle types (e.g., slow vs. fast), between a
diseased and non-diseased muscle, or importantly, to demonstrate the efficacy of
a muscle treatment such as a drug, an overexpressed transgene, or knockout of a
specific gene. Fundamental contractile properties can be assessed by twitch,
tetanic, force-frequency, force-velocity, and fatigue assays. Many of these
assays are conducted with the muscle at a constant length, e.g., an isometric
contraction. However, to better represent the dynamic purpose of muscles in vivo
(e.g., to move limbs), dynamic assays such as the force-velocity (concentric
contractions) or stretch-injury (eccentric contractions) should also be obtained.
Characterizing skeletal muscle function in vitro is a powerful approach to
demonstrate efficacy of a treatment to rescue diseased muscle and to assess
functional regeneration.
PMID- 27492180
TI - In Vivo Assessment of Muscle Contractility in Animal Studies.
AB - In patients with muscle injury or muscle disease, assessment of muscle damage is
typically limited to clinical signs, such as tenderness, strength, range of
motion, and more recently, imaging studies. Animal models provide unmitigated
access to histological samples, which provide a "direct measure" of damage.
However, even with unconstrained access to tissue morphology and biochemistry
assays, the findings typically do not account for loss of muscle function. Thus,
the most comprehensive measure of the overall health of the muscle is assessment
of its primary function, which is to produce contractile force. The majority of
animal models testing contractile force have been limited to the muscle groups
moving the ankle, with advantages and disadvantages depending on the equipment.
Here, we describe in vivo methods to measure torque, to produce a reliable muscle
injury, and to follow muscle function within the same animal over time. We also
describe in vivo methods to measure tension in the leg and thigh muscles.
PMID- 27492181
TI - Functional Measurement of Respiratory Muscle Motor Behaviors Using
Transdiaphragmatic Pressure.
AB - The diaphragm muscle must be able to generate sufficient forces to accomplish a
range of ventilatory and non-ventilatory behaviors throughout life. Measurements
of transdiaphragmatic pressure (Pdi) can be conducted during eupnea, hypoxia (10
% O2)-hypercapnia (5 % CO2), chemical airway stimulation (i.e., sneezing),
spontaneously occurring deep breaths (i.e., sighs), sustained airway or tracheal
occlusion, and maximal efforts elicited via bilateral phrenic nerve stimulation,
representing the full range of motor behaviors available by the diaphragm muscle.
We provide detailed methods on the in vivo measurements of Pdi in mice.
PMID- 27492183
TI - Analysis of Aerobic Respiration in Intact Skeletal Muscle Tissue by Microplate
Based Respirometry.
AB - Mitochondrial function is a key component of skeletal muscle health, and its
dysfunction has been associated with a wide variety of diseases. Microplate-based
respirometry measures aerobic respiration of live cells through extracellular
changes in oxygen concentration. Here, we describe a methodology to measure
aerobic respiration of intact murine skeletal muscle tissue. The tissues are not
cultured, permeabilized, or enzymatically dissociated to single fibers, so there
is minimal experimental manipulation affecting the samples prior to acquiring
measurements.
PMID- 27492182
TI - Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers.
AB - Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate
contractile behavior in a system that is greatly simplified, yet physiologically
relevant. Here we describe the steps required to prepare, permeabilize and
preserve small samples of skeletal muscle. We then detail the procedures used to
isolate individual fiber segments and attach them to an experimental apparatus
for the purpose of controlling activation and measuring force generation. We also
describe our technique for estimating the cross-sectional area of fiber segments.
The area measurement is necessary for normalizing the absolute force to obtain
specific force, a measure of the intrinsic force-generating capability of the
contractile system.
PMID- 27492184
TI - [Heterochromia and unilateral iris nodules].
PMID- 27492185
TI - Impact of disability status on suicide risks in South Korea: Analysis of National
Health Insurance cohort data from 2003 to 2013.
AB - BACKGROUND: The elevated risk of suicide in people with disability has been
suggested in the previous studies; however, the majority of study results have
been limited to specific disability types, and there is a lack of research
comparing the risk of suicide in people with disability in general. OBJECTIVES:
To examine the hazard ratio of suicide according to the presence and the types of
disability and identify patterns in the results. METHODS: In this study, we used
National Health Insurance Service-National Sample Cohort data on 990,598 people,
and performed analysis on the cause of death from 2003 through 2013. A Cox
proportional hazard model was used to estimate the hazard ratio of suicide
associated with disability and its types. RESULTS: The hazard ratio of suicide
among people with disability was 1.9-folds higher compared to people without
disability. The risk of suicide among different disability types was higher in
mental disorder, renal failure, brain injury and physical disability. The hazard
ratio of suicide in people with disability was not varied by income. The time to
death by suicide for people with disability from the onset of their disability
was 39.8 months on average. CONCLUSIONS: Our findings suggest that when the
government plans suicide prevention policies, early and additional interventions
specific to people with disability are needed. Disability due to mental disorder,
renal failure should be given priority.
PMID- 27492187
TI - Practical Counseling Skills for the Pediatrician in the Indian Context:
Correspondence.
PMID- 27492186
TI - Corynebacterium glutamicum possesses beta-N-acetylglucosaminidase.
AB - BACKGROUND: In Gram-positive Corynebacterium glutamicum and other members of the
suborder Corynebacterianeae, which includes mycobacteria, cell elongation and
peptidoglycan biosynthesis is mainly due to polar growth. C. glutamicum lacks an
uptake system for the peptidoglycan constituent N-acetylglucosamine (GlcNAc), but
is able to catabolize GlcNAc-6-phosphate. Due to its importance in white
biotechnology and in order to ensure more sustainable processes based on non-food
renewables and to reduce feedstock costs, C. glutamicum strains have previously
been engineered to produce amino acids from GlcNAc. GlcNAc also is a constituent
of chitin, but it is unknown if C. glutamicum possesses chitinolytic enzymes.
RESULTS: Chitin was shown here not to be growth substrate for C. glutamicum.
However, its genome encodes a putative N-acetylglucosaminidase. The nagA 2 gene
product was active as beta-N-acetylglucosaminidase with 0.27 mM 4-nitrophenyl
N,N'-diacetyl-beta-D-chitobioside as substrate supporting half-maximal activity.
NagA2 was secreted into the culture medium when overproduced with TAT and Sec
dependent signal peptides, while it remained cytoplasmic when overproduced
without signal peptide. Heterologous expression of exochitinase gene chiB from
Serratia marcescens resulted in chitinolytic activity and ChiB secretion was
enhanced when a signal peptide from C. glutamicum was used. Colloidal chitin did
not support growth of a strain secreting exochitinase ChiB and beta-N
acetylglucosaminidase NagA2. CONCLUSIONS: C. glutamicum possesses beta-N
acetylglucosaminidase. In the wild type, beta-N-acetylglucosaminidase activity
was too low to be detected. However, overproduction of the enzyme fused to TAT or
Sec signal peptides led to secretion of active beta-N-acetylglucosaminidase. The
finding that concomitant secretion of endogenous NagA2 and exochitinase ChiB from
S. marcescens did not entail growth with colloidal chitin as sole or combined
carbon source, may indicate the requirement for higher or additional enzyme
activities such as processive chitinase or endochitinase activities.
PMID- 27492188
TI - Influence of sperm DNA damage on human preimplantation embryo metabolism.
AB - Understanding the embryo metabolic response to sperm induced specific
abnormalities could help in developing the metabolic markers to prevent the
transfer of embryos carrying sperm mediated defects. In this study, NMR based
metabolic profiling of the embryo spent media was employed in 34 patients
undergoing ICSI cycles. Processed ejaculates were tested for DNA damage using
comet assay. Relative intensities of the metabolites from 74 embryo spent media
samples from 34 patients and 23 medium controls were profiled using 1H NMR and
compared between 'male-factor' and control groups. Relative intensities in the
subgroups which are independent of patients with male factor or tubal factors,
but related to the extent of sperm DNA damage were also compared. Sperm
characteristics including DNA damage levels (Olive tail moment, OTM) were
significantly different between 'male factor' and control groups (P<0.001
0.0001). Of the metabolites analyzed, glutamine intensity was significantly lower
in 'male factor' group (P<0.01) whereas, pyruvate intensity was significantly
lower in embryos derived from the processed sperm fraction having <1.0 OTM
(P=0.003). In contrast glutamine and alanine intensities were significantly
higher in the embryos derived from sperm population having OTM <1.0. (P=0.03 &
0.005 respectively). Pyruvate to alanine ratio was significantly lower in <1.0
OTM group (P<0.0001). This study indicates that increased level of sperm DNA
damage in the processed ejaculate affects embryo metabolism which could be
related to embryonic genetic integrity.
PMID- 27492189
TI - Posttraumatic Stress Disorder (PTSD) Patients Exhibit a Blunted Parasympathetic
Response to an Emotional Stressor.
AB - Diminished parasympathetic reactivity is a physiological feature of posttraumatic
stress disorder (PTSD). The objective of this study was to compare female PTSD
patients with non-traumatized healthy women with respect to autonomic
cardiovascular regulation during exposure to two stressors. Hospitalized PTSD
patients (n = 52) and controls (n = 37) completed standardized laboratory-based
stress testing including a mental arithmetic test and a standardized audiotape
recording of a crying infant. Controls and PTSD patients both showed a
significantly increased heart rate and reduced pre-ejection period from baseline
rest to the arithmetic stressor. However, as judged from nonsignificant changes
in baroreflex sensitivity, parasympathetic activation caused by the crying infant
stressor was blunted in PTSD patients as compared to healthy individuals. Under
the crying infant condition, a vagal dominance was observed only in controls, and
not in PTSD patients. Our data demonstrate that, in PTSD patients, diminished
parasympathetic reactivity is not restricted to trauma-related events but can
also be observed in response to a social stimulus such as listening to a crying
infant. This finding suggests that the altered vagal reactivity in PTSD patients
reflects the physiological consequences of a generally disturbed autonomous
response to emotionally relevant stressors.
PMID- 27492190
TI - Arguing against the proposed definition changes of PD.
AB - As members of the Lewy Body Dementia Association Scientific Advisory Council, we
aim to address some of the issues raised in the article titled "Time to Redefine
PD? Introductory Statement of the MDS Task Force on the Definition of Parkinson's
Disease." In particular, we suggest that the 1-year rule distinguishing
Parkinson's disease dementia from dementia with Lewy bodies is worth maintaining
because it serves an important purpose in clinical practice and clinical and
basic science research and when helping the lay community understand the
complexity of these different clinical phenotypes. Furthermore, we believe that
adding an additional diagnostic label, "PD (dementia with Lewy bodies subtype),"
will confuse rather than clarify the distinction between dementia with Lewy
bodies and PD or PD dementia, and will not improve management or expedite
therapeutic development. We present arguments supporting our contentions. (c)
2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on
behalf of International Parkinson and Movement Disorder Society.
PMID- 27492192
TI - State diagram for adhesion dynamics of deformable capsules under shear flow.
AB - Due to the significance of understanding the underlying mechanisms of cell
adhesion in biological processes and cell capture in biomedical applications, we
numerically investigate the adhesion dynamics of deformable capsules under shear
flow by using a three-dimensional computational fluid dynamic model. This model
is based on the coupling of the front tracking-finite element method for elastic
mechanics of the capsule membrane and the adhesion kinetics simulation for
adhesive interactions between capsules and functionalized surfaces. Using this
model, three distinct adhesion dynamic states are predicted, such as detachment,
rolling and firm-adhesion. Specifically, the effects of capsule deformability
quantified by the capillary number on the transitions of these three dynamic
states are investigated by developing an adhesion dynamic state diagram for the
first time. At low capillary numbers (e.g. Ca < 0.0075), whole-capsule
deformation confers the capsule a flattened bottom in contact with the
functionalized surface, which hence promotes the rolling-to-firm-adhesion
transition. It is consistent with the observations from previous studies that
cell deformation promotes the adhesion of cells lying in the rolling regime.
However, it is surprising to find that, at relatively high capillary numbers
(e.g. 0.0075 < Ca < 0.0175), the effect of capsule deformability on its adhesion
dynamics is far more complex than just promoting adhesion. High deformability of
capsules makes their bottom take a concave shape with no adhesion bond formation
in the middle. The appearance of this specific capsule shape inhibits the
transitions of both rolling-to-firm-adhesion and detachment-to-rolling, and it
means that capsule deformation no longer promotes the capsule adhesion. Besides,
it is interesting to note that, when the capillary number exceeds a critical
value (e.g. Ca = 0.0175), the rolling state no longer appears, since capsules
exhibit large deviation from the spherical shape.
PMID- 27492191
TI - Regulation of macrophage polarization and plasticity by complex activation
signals.
AB - Macrophages are versatile cells of the immune system that play an important role
in both advancing and resolving inflammation. Macrophage activation has been
described as a continuum, and different stimuli lead to M1, M2, or mixed
phenotypes. In addition, macrophages expressing markers associated with both M1
and M2 function are observed in vivo. Using flow cytometry, we examine how
macrophage populations respond to combined M1 and M2 activation signals,
presented either simultaneously or sequentially. We demonstrate that macrophages
exposed to a combination of LPS, IFN-gamma, IL-4, and IL-13 acquire a mixed
activation state, with individual cells expressing both M1 marker CD86 and M2
marker CD206 instead of polarizing to discrete phenotypes. Over time, co
stimulated macrophages lose expression of CD86 and display increased expression
of CD206. In addition, we find that exposure to LPS/IFN-gamma potentiates the
subsequent response to IL-4/IL-13, whereas pre-polarization with IL-4/IL-13
inhibits the response to LPS/IFN-gamma. Mathematical modeling of candidate
regulatory networks indicates that a complex inter-dependence of M1- and M2
associated pathways underlies macrophage activation. Specifically, a mutual
inhibition motif was not by itself sufficient to reproduce the temporal marker
expression data; incoherent feed-forward of M1 activation as well as both
inhibition and activation of M2 by M1 were required. Together these results
corroborate a continuum model of macrophage activation and demonstrate that
phenotypic markers evolve with time and with exposure to complex signals.
PMID- 27492193
TI - Anti-inflammatory properties of pterocarpanquinone LQB-118 in mice.
AB - Pterocarpanquinone (+/-)-LQB-118 presents antineoplastic and antiparasitic
properties and also shows great inhibitory effect on TNF-alpha release in vitro.
Here, its anti-inflammatory activity was evaluated in a lipopolysaccharide (LPS)
induced lung inflammation model in C57BL/6 mice. LPS inhalation induced a marked
neutrophil infiltration to the lungs which was reduced by intraperitoneal
treatment with (+/-)-LQB-118 in a similar manner to that of dexamethasone and
even better than that of acetylsalicylic acid. Moreover, (+/-)-LQB-118
administration resulted in decrease of NF-kappaB activation and KC level in
lungs, with a pronounced inhibitory effect on TNF-alpha release, measured in
bronchoalveolar lavage fluid. Trying to understand the anti-inflammatory
mechanism by which (+/-)-LQB-118 acts, we performed a molecular modeling
analysis, including docking to estrogen receptors alpha and beta. Results
suggested that (+/-)-LQB-118 may bind to both receptors, with a similar
orientation to 17-beta-estradiol. Together, these results showed that (+/-)-LQB
118 exhibits an anti-inflammatory effect, most likely by inhibiting TNF-alpha
release and NF-kappaB activation, which may be related to the estrogen receptor
binding.
PMID- 27492194
TI - 3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease
inhibitors: Synthesis, molecular docking and biological evaluation.
AB - Helicobacter pylori urease is involved in several physiologic responses such as
stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus,
inhibition of urease is taken for a good chance to treat H. pylori-caused
infections, we have therefore focused our efforts on seeking novel urease
inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and
evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5
chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active
inhibitor with IC50 of 0.15+/-0.05MUM, showing a mixed inhibition with both
competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives
kinetics parameters of 0.13 and 0.12MUg.mL(-1) for Ki and Ki', respectively. The
plasma protein binding assays suggested that d24 exhibited moderate binding to
human and rabbit plasma proteins.
PMID- 27492195
TI - Cholinesterase inhibitory activity of isoquinoline alkaloids from three
Cryptocarya species (Lauraceae).
AB - Alzheimer's disease is the most common form of dementia among older adults.
Acetylcholinesterase and butyrylcholinesterase are two enzymes involved in the
breaking down of the neurotransmitter acetylcholine. Inhibitors for these enzymes
have potential to prolong the availability of acetylcholine. Hence, the search
for such inhibitors especially from natural products is needed in developing
potential drugs for Alzheimer's disease. The present study investigates the
cholinesterase inhibitory activity of compounds isolated from three Cryptocarya
species towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
Nine alkaloids were isolated; (+)-nornantenine 1, (-)-desmethylsecoantofine 2,
(+)-oridine 3, (+)-laurotetanine 4 from the leaves of Cryptocarya densiflora BI.,
atherosperminine 5, (+)-N-methylisococlaurine 6, (+)-N-methyllaurotetanine 7 from
the bark of Cryptocarya infectoria Miq., 2-methoxyatherosperminine 8 and (+)
reticuline 9 from the bark of Cryptocarya griffithiana Wight. In general, most of
the alkaloids showed higher inhibition towards BChE as compared to AChE. The
phenanthrene type alkaloid; 2-methoxyatherosperminine 8, exhibited the most
potent inhibition against BChE with IC50 value of 3.95MUM. Analysis of the
Lineweaver-Burk (LB) plot of BChE activity over a range of substrate
concentration suggested that 2-methoxyatherosperminine 8 exhibited mixed-mode
inhibition with an inhibition constant (Ki) of 6.72MUM. Molecular docking studies
revealed that 2-methoxyatherosperminine 8 docked well at the choline binding site
and catalytic triad of hBChE (butyrylcholinesterase from Homo sapiens); hydrogen
bonding with Tyr 128 and His 438 residues respectively.
PMID- 27492196
TI - The development of peptide ligands that target helix 69 rRNA of bacterial
ribosomes.
AB - Antibiotic resistance prevents successful treatment of common bacterial
infections, making it clear that new target locations and drugs are required to
resolve this ongoing challenge. The bacterial ribosome is a common target for
antibacterials due to its essential contribution to cell viability. The focus of
this work is a region of the ribosome called helix 69 (H69), which was recently
identified as a secondary target site for aminoglycoside antibiotics. H69 has key
roles in essential ribosomal processes such as subunit association, ribosome
recycling, and tRNA selection. Conserved across phylogeny, bacterial H69 also
contains two pseudouridines and one 3-methylpseudouridine. Phage display revealed
a heptameric peptide sequence that targeted H69. Using solid-phase synthesis,
peptide variants with higher affinity and improved selectivity to modified H69
were generated. Electrospray ionization mass spectrometry was used to determine
relative apparent dissociation constants of the RNA-peptide complexes.
PMID- 27492197
TI - The life cycle of Thelohanellus kitauei (Myxozoa: Myxosporea) infecting common
carp (Cyprinus carpio) involves aurantiactinomyxon in Branchiura sowerbyi.
AB - Thelohanellus kitauei is a freshwater myxosporean parasite causing intestinal
giant cystic disease of common carp. To clarify the life cycle of T. kitauei, we
investigated the oligochaete populations in China and Hungary. This study
confirms two distinct aurantiactinomyxon morphotypes (Aurantiactinomyxon type 1
and Aurantiactinomyxon type 2) from Branchiura sowerbyi as developmental stages
of the life cycle of T. kitauei. The morphological characteristics and DNA
sequences of these two types are described here. Based on 18S rDNA sequence
analysis, Aurantiactinomyxon type 1 (2048 bp) and Aurantiactinomyxon type 2 (2031
bp) share 99.2-99.4 %, 99.8-100 % similarity to the published sequences of T.
kitauei, respectively. The 18S rDNA sequences of these two aurantiactinomyxon
morphotypes share 99.4 % similarity, suggesting intraspecific variation within
the taxon, possibly due to geographic origin. Phylogenetic analyses demonstrate
the two aurantiactinomyxon types clustered with T. kitauei. Regardless, based on
18S rDNA synonymy, it is likely that Aurantiactinomyxon type 1 and 2 are
conspecific with T. kitauei. This is the fourth elucidated two-host life cycle of
Thelohanellus species and the first record of T. kitauei in Europe.
PMID- 27492198
TI - Sinuolinea niloticus n. sp., a myxozoan parasite that causes disease in Nile
tilapia (Oreochromis niloticus).
AB - Sinuolinea species are myxozoans of the order Bivalvulida, suborder Variisporina,
and family Sinuolineidae, which can be parasites for freshwater and marine fish.
The aim of this study was to describe the occurrence of Sinuolinea niloticus n.
sp. infecting Nile tilapia (Oreochromis niloticus) from aquaculture and from
river sources with morphological and molecular analyses. Between March 2010 and
November 2012, 116 Nile tilapia were randomly sampled from aquaculture net
fishing (n = 56) in Mira Estrela, Sao Paulo, and from the Capivari River (n = 60)
in Botucatu, Sao Paulo. The fishes that were sampled were examined by necropsy,
microscopic observation and molecular techniques for detection and identification
of the myxozoan causing disease in tilapia. All of the tissues that were sampled
for analysis showed the presence of the parasite. It was observed by microscopy
that the myxozoan belongs to the Sinuolinea genus. This identification was
performed based on morphological characteristics and histopathology findings,
such as structures consistent with myxozoan in the interstices in all analysed
tissues, coagulative necrosis, haemorrhage, inflammatory processes, presence of
melano-macrophages and eosinophils. The results of the molecular analyses
revealed that the myxozoan detected and identified in this study is sister to a
group of other Sinuolinea species. Because this is the first report of this
parasite in Nile tilapia, the parasite was named S. niloticus n. sp. This is the
first report of a Sinuolinea species in Brazil and in tilapia.
PMID- 27492199
TI - Morphological and molecular identification of nasopharyngeal bot fly larvae
infesting red deer (Cervus elaphus) in Austria.
AB - Nasopharyngeal myiases are caused by larvae of bot flies (Diptera: Oestridae),
which have evolved a high specificity for their hosts. Bot flies (n = 916) were
collected from 137 (57.6 %) out of 238 red deer (Cervus elaphus) hunted in
Vorarlberg and Tyrol (Western Austria). After being stored in 75 % ethanol,
larvae were identified to species level and developmental stage using
morphological and morphometric keys. Larvae were also molecularly characterized
by polymerase chain reaction (PCR) amplification and partial sequencing of the
mitochondrial cytochrome oxidase subunit I gene. Morphological and molecular
analysis allowed identification of larvae as Cephenemyia auribarbis and
Pharyngomyia picta. Genetic variations were also examined within the specimens
collected in both geographical locations.
PMID- 27492200
TI - Antimalarial potential of leaves of Chenopodium ambrosioides L.
AB - In an effort to identify novel therapeutic alternatives for the treatment of
malaria, the present study evaluated the antimalarial effect of the crude
hydroalcoholic extract (HCE) from the leaves of Chenopodium ambrosioides L. For
this purpose, the molecular affinity between the total proteins from erythrocytes
infected with Plasmodium falciparum and HCE or chloroquine was evaluated by
surface plasmon resonance (SPR). Subsequently, the plasmodicidal potential of HCE
was assessed in a P. falciparum culture. Using BALB/c mice infected with
Plasmodium berghei intraperitoneally (ip.), we evaluated the effects of ip.
treatment, for three consecutive days (day 7, 8, and 9 after infection), with
chloroquine (45 mg/kg) or HCE (5 mg/kg), considering the survival index and the
parasitaemia. The groups were compared to an untreated control group that
receives only PBS at the same periods. The results indicated that HCE could bind
to the total proteins of infected erythrocytes and could inhibit the parasite
growth in vitro (IC50 = 25.4 g/mL). The in vivo therapeutic treatment with HCE
increased the survival and decreased the parasitaemia in the infected animals.
Therefore, the HCE treatment exhibited a significant antiplasmodial effect and
may be considered as a potential candidate for the development of new
antimalarial drugs.
PMID- 27492201
TI - Microbiota from Rhabditis regina may alter nematode entomopathogenicity.
AB - Here we report the presence of the entomopathogenic nematode Rhabditis
(Rhabditoides) regina affecting white grubs (Phyllophaga sp. and Anomala sp.) in
Mexico and R. regina-associated bacteria. Bioassays were performed to test the
entomopathogenic capacity of dauer and L2 and L3 (combined) larval stages.
Furthermore, we determined the diversity of bacteria from laboratory nematodes
cultivated for 2 years (dauer and L2-L3 larvae) and from field nematodes (dauer
and L2-L3 larvae) in addition to the virulence in Galleria mellonella larvae of
some bacterial species from both laboratory and field nematodes. Dauer and non
dauer larvae of R. regina killed G. mellonella. Bacteria such as Serratia sp.
(isolated from field nematodes) and Klebsiella sp. (isolated from larvae of
laboratory and field nematodes) may explain R. regina entomopathogenic
capabilities. Different bacteria were found in nematodes after subculturing in
the laboratory suggesting that R. regina may acquire bacteria in different
environments. However, there were some consistently found bacteria from
laboratory and field nematodes such as Pseudochrobactrum sp., Comamonas sp.,
Alcaligenes sp., Klebsiella sp., Acinetobacter sp., and Leucobacter sp. that may
constitute the nematode microbiome. Results showed that some bacteria
contributing to entomopathogenicity may be lost in the laboratory representing a
disadvantage when nematodes are cultivated to be used for biological control.
PMID- 27492202
TI - Cardiac and respiration induced motion of mediastinal lymph node targets in lung
cancer patients throughout the radiotherapy treatment course.
AB - BACKGROUND AND PURPOSE: Involved mediastinal lymph nodes (LNs) are often included
in the radiotherapy target for lung cancer patients. Their motion may differ from
the primary tumor motion, possibly undermining the loco-regional control. This
study determines the detailed differential target motion throughout the treatment
course. MATERIAL AND METHODS: Ten lung cancer patients with 2-4 fiducial markers
implanted in LN targets received IMRT with a daily pre-treatment cone-beam CT
(CBCT) scan. Offline, the 3D trajectory of the markers was determined from their
projected trajectory in the CBCT projections. Frequency analysis was performed to
separate the intrafraction motion into a respiratory and cardiac component. The
mean setup error of the markers and the motion range were used to calculate
margins required for LN targets when setup is based on soft-tissue match.
RESULTS: Respiration motion was largest in the CC direction and more prominent
for more caudal LNs. Cardiac motion was often (73%) largest in the AP direction
and tended to be largest for more cranial LNs. Margins for intrafraction motion
and daily baseline shifts of LNs were 4.8mm (LR), 6.0mm (CC) and 6.7mm (AP).
CONCLUSIONS: Detailed mapping showed that LN motion was in general governed by
breathing, but some LNs had substantial cardiac induced motion.
PMID- 27492203
TI - Comparative evaluation of respiratory-gated and ungated FDG-PET for target volume
definition in radiotherapy treatment planning for pancreatic cancer.
AB - OBJECTIVE: The purpose of this study was to evaluate the usefulness of
respiratory-gated positron emission tomography (4D-PET) in pancreatic cancer
radiotherapy treatment planning (RTTP). MATERIALS AND METHODS: Fourteen patients
with 18F-fluorodeoxyglucose (FDG)-avid pancreatic tumours were evaluated between
December 2013 and March 2015. Two sets of volumes were contoured for the
pancreatic tumour of each patient. The biological target volume in three
dimensional RTTP (BTV3D) was contoured using conventional respiratory un-gated
PET. The BTV3D was then expanded using population-based margins to generate a
series of internal target volume 3D (ITV3D) values. The ITV 4D (ITV4D) was
contoured using 4D-PET. Each of the five phases of 4D-PET was used for 4D
contouring, and the ITV4D was constructed by summing the volumes defined on the
five individual 4D-PET images. The relative volumes and normalized volumetric
overlap were computed between ITV3D and ITV4D. RESULTS: On average, the FDG-avid
tumour volumes were 1.6 (range: 0.8-2.3) fold greater in the ITV4D than in the
BTV3D. On average, the ITV3D values were 2.0 (range: 1.1-3.4) fold larger than
the corresponding ITV4D values. CONCLUSION: The ITV generated from 4D-PET can be
used to improve the accuracy or reduce normal tissue irradiation compared with
conventional un-gated PET-based ITV.
PMID- 27492204
TI - Post radiation hysterectomy in locally advanced cervical cancer: Outcomes and
dosimetric impact.
AB - PURPOSES: Firstly, to evaluate the impact of completion hysterectomy after
chemoradiation and image-guided adaptive brachytherapy (IGABT) in locally
advanced cervical cancer. Secondly, to assess a potential differential dose
effect relationship for the rectum and bladder according to the realization of
hysterectomy. MATERIAL AND METHODS: Two cohorts of patients were identified,
differing by the realization of completion hysterectomy. Inclusions were limited
to FIGO stage I-II, with no para-aortic involvement. All patients received a
combination of pelvic chemoradiation followed by IGABT. Their outcomes and
morbidity were reviewed. Log-rank tests were used to compare survivals. Probit
analyses were performed to study dose-volume effect relationships. RESULTS: The
two cohorts comprised 54 patients in the completion surgery group and 157
patients in the definitive radiotherapy group. They were well balanced, except
for the mean follow-up, significantly longer in the post hysterectomy cohort and
the use of PET-CT in the work-up, more frequent in the definitive radiotherapy
cohort. Although less local relapses were reported in the hysterectomy group, the
5-year disease-free and overall survival did not differ between groups. The
cumulative incidence of severe late morbidity was significantly increased in the
hysterectomy cohort: 22.5% versus 6.5% at 5years (p=0.016). Dose-volume effects
were observed for the bladder, with the D2cm3 corresponding with a 10%
probability of late severe morbidity urinary events (ED10) of 67.8Gy and 91.9Gy
in the hysterectomy and definitive radiotherapy cohorts, respectively. A D90
CTVHR of 85Gy (planning aim) corresponded with a 93.3% rate of local control in
the definitive radiotherapy cohort whereas it corresponded with a 77.3% chance to
have a good histologic response (complete response or microscopic residual
disease) in the hysterectomy group. CONCLUSION: No benefit from completion
hysterectomy in terms of overall or disease-free survival rates was observed,
which was moreover responsible for an increase of the severe late morbidity. The
realization of post-radiation hysterectomy resulted in a shift of the ED10 of
24.1Gy.
PMID- 27492205
TI - Measurement of transepidermal water loss (TEWL) in cats with experimental skin
barrier dysfunction using a closed chamber system.
AB - BACKGROUND: A closed chamber evaporimeter is suitable for measuring
transepidermal water loss (TEWL) in cats because of the compact device size,
tolerance to sudden movement and short measuring time. TEWL is a representative
parameter for skin barrier dysfunction, which is one of the clinical signs of
atopic dermatitis in humans and dogs. Measurement of feline TEWL has been
reported, but applicability of this parameter has not been validated.
HYPOTHESIS/OBJECTIVES: The aims of this study were to determine if tape stripping
is a valid experimental model in cats for studying TEWL and to determine if a
closed chambered system is a suitable measurement tool for cats. ANIMALS: Ten
clinically normal cats. METHODS: In order to evaluate variation of the measured
values, TEWL was measured at the right and left side of the three clipped regions
(axillae, lateral thigh and groin). Subsequently, TEWL was measured using
sequential tape stripping of the stratum corneum as a model of acute barrier
disruption. RESULTS: The variations between both sides of the three regions
showed no significant difference. Sequential tape stripping was associated with
increasing values for TEWL. CONCLUSIONS AND CLINICAL IMPORTANCE: Feline TEWL was
shown to reflect changes in the skin barrier in an experimental model using a
closed chamber system and has the potential for evaluating skin barrier function
in cats with skin diseases.
PMID- 27492206
TI - Different Variants in Reverse Transcriptase Domain Determined by Ultra-deep
Sequencing in Treatment-naive and Treated Indonesian Patients Infected with
Hepatitis B Virus.
AB - A nucleos(t)ide analog (NA) is the common antiviral drug available for directly
treating hepatitis B virus (HBV) infection. However, its application has led to
the emergence of NA-resistant mutations mostly in a conserved region of the
reverse transcriptase domain of HBV polymerase. Harboring NA-resistant mutations
decreases drug effectiveness and increases the frequency of end-stage liver
disease. The invention of next-generation sequencing that can generate thousands
of sequences from viral complex mixtures provides opportunities to detect minor
changes and early viral evolution under drug stress. The present study used ultra
deep sequencing to evaluate discrepant quasispecies in the reverse transcriptase
domain of HBV including NA-resistant hotspots between seven treatment-naive
Indonesian patients infected with HBV and five at the early phase of treatment.
The most common sub-genotype was HBV B3 (83.34%). The substitution rate of
variants determined among amino acids with a ratio of >= 1% changes was higher
among the population in conserved regions (23.19% vs. 4.59%, P = 0.001) and in
the inter-reverse transcriptase domain (23.95% vs. 2.94%, P = 0.002) in treatment
naive, than in treated patients. Nine hotspots of antiviral resistance were
identified in both groups, and the mean frequency of changes in all patients was
< 1%. The known rtM204I mutation was the most frequent in both groups. The lower
rate of variants in HBV quasispecies in patients undergoing treatment could be
associated with virus elimination and the extinction of sensitive species by NA
therapy. The present findings imply that HBV quasispecies dynamically change
during treatment.
PMID- 27492207
TI - Thrombospondin 1 Suppresses Insulin Signaling in C2C12 Myotubes.
AB - Thrombospondin 1 (TSP-1) is abundantly expressed in visceral adipose tissue and
this expression is up-regulated in obese humans and rodents. Recent studies
showed that genetic deletion of TSP-1 protects mice from diet-induced insulin
resistance. However, the molecular mechanism is largely unknown. In this study,
we examined the effect of recombinant TSP-1 on insulin signaling in cultured
cells from insulin sensitive tissues to investigate whether TSP-1 could act as an
adipokine. Here we show that treatment with recombinant TSP-1 suppressed insulin
signaling in cultured muscle cells, which was accompanied by the activation of
stress signaling such as JNK, p38, and IKK. These results suggest that TSP-1 acts
as an adipokine which is involved in the pathogenesis of obesity-induced insulin
resistance. Thus, TSP-1 could be a potential target for the treatment of insulin
resistance and metabolic disease related to insulin resistance.
PMID- 27492208
TI - Recurrence of Enchondroma in a Middle Finger after Curettage and Back-filling
with Calcium Phosphate Bone Cement: a Case Report.
AB - We report a case of recurrence of enchondroma in a middle finger after curettage
and back-filling with calcium phosphate bone cement (CPC). The radiograph showed
a lytic lesion around the CPC filling which showed no signs of absorption after
12 years. The tumor was curated easily, however, a steel bar was needed to remove
the CPC mass in a carefully manner not to break the cortex. CPC has an advantage
of immediate biomechanical stability, on the other hand, a disadvantage of being
unabsorbed inside of bone. Although enchondroma has a low recurrence rate after
surgery generally, in consideration of recurrence, we recommend the use of
absorbable materials when a use of artificial bone substitute to fill the defect
is planned.
PMID- 27492209
TI - A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver
Transplantation.
AB - There are few descriptions of severe thrombocytopenia during the early
postoperative period after liver transplantation, and these have not been fully
documented in the literature. Here, we report a case of drug-induced
thrombocytopenia requiring transfusion of blood products after living donor liver
transplantation. We determined that this was not caused by the interferon-free
anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related
cirrhosis and hepatorenal syndrome underwent living donor liver transplantation
using a left lobe graft from her son. After transplantation, immunosuppression
consisted of tacrolimus and steroid. Seven weeks after transplantation,
interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen
days thereafter, hepatitis C virus tested negative. However, the platelet count
had begun to gradually decrease just before starting anti-viral therapy.
Daclatasvir and asunaprevir were stopped because this was suspected to be a side
effect of these drugs, but the patient nonetheless went on to develop severe
thrombocytopenia (platelet count 17,000/MUL), which needed transfusions. Now
suspecting tacrolimus as the inducer of this side effect, we changed to
cyclosporin, after which the platelet count gradually recovered. Viral markers
were still not detectable up to 2 months after discontinuation of the antiviral
drugs. We conclude that when severe thrombocytopenia occurs, possible drug
induced thrombocytopenia as well as other disorders must be investigated.
PMID- 27492210
TI - Heterogeneous Effects of a Nonlinear Price Schedule for Outpatient Care.
AB - Nonlinear price schedules generally have heterogeneous effects on health-care
demand. We develop and apply a finite mixture bivariate probit model to analyze
whether there are heterogeneous reactions to the introduction of a nonlinear
price schedule in the German statutory health insurance system. In administrative
insurance claims data from the largest German health insurance plan, we find that
some individuals strongly react to the new price schedule while a second group of
individuals does not react. Post-estimation analyses reveal that the group of the
individuals who do not react to the reform includes the relatively sick. These
results are in line with forward-looking behavior: Individuals who are already
sick expect that they will hit the kink in the price schedule and thus are less
sensitive to the co-payment. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27492211
TI - Polylactides in additive biomanufacturing.
AB - New advanced manufacturing technologies under the alias of additive
biomanufacturing allow the design and fabrication of a range of products from pre
operative models, cutting guides and medical devices to scaffolds. The process of
printing in 3 dimensions of cells, extracellular matrix (ECM) and biomaterials
(bioinks, powders, etc.) to generate in vitro and/or in vivo tissue analogue
structures has been termed bioprinting. To further advance in additive
biomanufacturing, there are many aspects that we can learn from the wider
additive manufacturing (AM) industry, which have progressed tremendously since
its introduction into the manufacturing sector. First, this review gives an
overview of additive manufacturing and both industry and academia efforts in
addressing specific challenges in the AM technologies to drive toward AM-enabled
industrial revolution. After which, considerations of poly(lactides) as a
biomaterial in additive biomanufacturing are discussed. Challenges in wider
additive biomanufacturing field are discussed in terms of (a) biomaterials; (b)
computer-aided design, engineering and manufacturing; (c) AM and additive
biomanufacturing printers hardware; and (d) system integration. Finally, the
outlook for additive biomanufacturing was discussed.
PMID- 27492212
TI - Electronic relaxation dynamics of PCDA-PDA studied by transient absorption
spectroscopy.
AB - Photo-curable polymers originating from 10,12-pentacosadiynoic acid (PCDA-PDA)
are commonly used polydiacetylenes (PDAs). PCDA-PDA exhibits thermochromic
properties undergoing a unique colorimetric transition from blue to red as the
temperature is increased from low to high. In this work, we have carefully
studied the temperature-dependent optical properties of PCDA-PDA by using UV
visible absorption, FTIR, Raman, and transient absorption (TA) spectroscopy in
combination with quantum chemical calculations. Temperature-dependent UV-visible
absorption spectra indicate that PCDA-PDA exhibits reversible thermochromic
properties up to 60 degrees C and its thermochromic properties become
irreversible above 60 degrees C. Such distinct thermochromic properties are also
manifested in TA signals so that the electronically excited PCDA-PDA relaxes to
the ground state via an intermediate state at 20 degrees C (blue form) but it
relaxes directly back to the ground state at 80 degrees C (red form). The
electronic relaxation dynamics of PCDA-PDA are comprehensively analyzed based on
different kinetic models by using the global fitting analysis method. The
intermediate state in the blue form of PCDA-PDA is clearly found to be
responsible for fluorescence quenching. FTIR and Raman spectroscopy and quantum
chemical calculations confirm that the H-bonds between the carboxylic acid groups
in PCDA-PDA are broken at high temperatures leading to an irreversible structural
change of PCDA-PDA.
PMID- 27492213
TI - Quantitative analysis of aromatics for synthetic biology using liquid
chromatography.
AB - The replacement of petrochemical aromatics with bio-based molecules is a key area
of current biotechnology research. To date, a small number of aromatics have been
produced by recombinant bacteria in laboratory scale while industrial production
still requires further strain development. While each study includes some
distinct analytical methodology to quantify certain aromatics, a method that can
reliably quantify a great number of aromatic products and relevant pathway
intermediates is needed to accelerate strain development. In this study, we
developed a robust reverse phase high performance liquid chromatography method to
quantify a wide range of aromatic metabolites present in host microorganisms
using the shikimate pathway, which is the major metabolic pathway for
biosynthesis of aromatics. Twenty-three metabolites can be quantified precisely
with the optimized method using standard HPLC equipment and UV detection, with
the mobile phase used for chromatography also compatible with mass spectrometry
(MS). The limit of quantification/detection is as low as 10-10 to 10-13 mol,
respectively, which makes this method feasible for quantification of
intracellular metabolites. This method covers most metabolic routes for aromatics
biosynthesis, it is inexpensive, robust, simple, precise and sensitive, and has
been demonstrated on cell extracts from S. cerevisiae genetically engineered to
overproduce aromatics.
PMID- 27492214
TI - Resistance: How to resist immunotherapy.
PMID- 27492216
TI - Metastasis: Setting up a new home.
PMID- 27492217
TI - B-cell-specific depletion of tumour necrosis factor alpha inhibits
atherosclerosis development and plaque vulnerability to rupture by reducing cell
death and inflammation.
AB - AIMS: B2 lymphocytes promote atherosclerosis development but their mechanisms of
action are unknown. Here, we investigated the role of tumour necrosis factor
alpha (TNF-alpha) produced by B2 cells in atherogenesis. METHODS AND RESULTS: We
found that 50% of TNF-alpha-producing spleen lymphocytes were B2 cells and ~20%
of spleen and aortic B cells produced TNF-alpha in hyperlipidemic ApoE(-/-) mice.
We generated mixed bone marrow (80% MUMT/20% TNF-alpha(-/-)) chimeric LDLR(-/-)
mice where only B cells did not express TNF-alpha. Atherosclerosis was reduced in
chimeric LDLR(-/-) mice with TNF-alpha-deficient B cells. TNF-alpha expression in
atherosclerotic lesions and in macrophages were also reduced accompanied by fewer
apoptotic cells, reduced necrotic cores, and reduced lesion Fas, interleukin
1beta and MCP-1 in mice with TNF-alpha-deficient B cells compared to mice with
TNF-alpha-sufficient B cells. To confirm that the reduced atherosclerosis is
attributable to B2 cells, we transferred wild-type and TNF-alpha-deficient B2
cells into ApoE(-/-) mice deficient in B cells or in lymphocytes. After 8 weeks
of high fat diet, we found that atherosclerosis was increased by wild-type but
not TNF-alpha-deficient B2 cells. Lesions of mice with wild-type B2 cells but not
TNF-alpha-deficient B2 cells also had increased apoptotic cells and necrotic
cores. Transferred B2 cells were found in lesions of recipient mice, suggesting
that TNF-alpha-producing B2 cells promote atherosclerosis within lesions.
CONCLUSION: We conclude that TNF-alpha produced by B2 cells is a key mechanism by
which B2 cells promote atherogenesis through augmenting macrophage TNF-alpha
production to induce cell death and inflammation that promote plaque
vulnerability.
PMID- 27492218
TI - Efficacy of scalp hair decontamination following exposure to vapours of sulphur
mustard simulants 2-chloroethyl ethyl sulphide and methyl salicylate.
AB - Chemical warfare agents are an actual threat and victims' decontamination is a
main concern when mass exposure occurs. Skin decontamination with current
protocols has been widely documented, as well as surface decontamination.
However, considering hair ability to trap chemicals in vapour phase, we
investigated hair decontamination after exposure to sulphur mustard simulants
methyl salicylate and 2-chloroethyl ethyl sulphide. Four decontamination
protocols were tested on hair, combining showering and emergency decontamination
(use of Fuller's earth or Reactive Skin Decontamination Lotion RSDL(r)). Both
simulants were recovered from hair after treatment, but contents were
significantly reduced (42-85% content allowance). Showering alone was the least
efficient protocol. Concerning 2-chloroethyl ethyl sulphide, protocols did not
display significant differences in decontamination efficacy. For MeS, use of
emergency decontaminants significantly increased showering efficacy (10-20%
rise), underlining their usefulness before thorough decontamination. Our results
highlighted the need to extensively decontaminate hair after chemical exposure.
Residual amounts after decontamination are challenging, as their release from
hair could lead to health issues.
PMID- 27492219
TI - Transient anomalous diffusion in periodic systems: ergodicity, symmetry breaking
and velocity relaxation.
AB - We study far from equilibrium transport of a periodically driven inertial
Brownian particle moving in a periodic potential. As detected for a SQUID ratchet
dynamics, the mean square deviation of the particle position from its average may
involve three distinct intermediate, although extended diffusive regimes:
initially as superdiffusion, followed by subdiffusion and finally, normal
diffusion in the asymptotic long time limit. Even though these anomalies are
transient effects, their lifetime can be many, many orders of magnitude longer
than the characteristic time scale of the setup and turns out to be
extraordinarily sensitive to the system parameters like temperature or the
potential asymmetry. In the paper we reveal mechanisms of diffusion anomalies
related to ergodicity of the system, symmetry breaking of the periodic potential
and ultraslow relaxation of the particle velocity towards its steady state.
Similar sequences of the diffusive behaviours could be detected in various
systems including, among others, colloidal particles in random potentials, glass
forming liquids and granular gases.
PMID- 27492220
TI - Diffusion-weighted MRI for detection of hepatic osteodystrophy in primary
sclerosing cholangitis: a comparison study with dual-energy X-ray absorptiometry.
AB - PURPOSE: Osteodystrophy is a frequent complication in primary sclerosing
cholangitis (PSC). The aim was to test the feasibility of vertebral bone
diffusion-weighted imaging (DWI) in routine liver MRI for detection of
osteoporosis using dual-energy X-ray absorptiometry (DXA) as gold standard.
MATERIALS AND METHODS: Forty PSC patients (50 +/- 12.6 years) and ten controls
(49.5 +/- 13.0 years) were scanned using a DWI spin echo echo-planar sequence (b
factors 0-800 s/mm2) on a 3-T MRI system and DXA (76 kVp). The apparent diffusion
coefficient (ADC) and T-score were correlated to laboratory and clinical details
using Pearson correlation. RESULTS: In DXA-diagnosed osteoporosis (n = 3) and
osteopenia (n = 12), the mean ADC was decreased (0.26 +/- 0.03 and 0.30 +/- 0.07
* 10-3 mm2/s) compared to patients with normal DXA scan results (n = 25; 0.32 +/-
0.06 * 10-3 mm2/s). No significant correlation of the ADC and T-score (r = 0.24;
p = 0.13) was found, but the T-score correlated significantly to disease duration
(r = -0.33; p = 0.04). In patients with prednisolone therapy (n = 7), the DXA T
score was significantly lower (-1.46 +/- 0.49 vs. -0.16 +/- 0.23; p = 0.03).
CONCLUSION: Diffusion-weighted MRI of the vertebral spine is a feasible technic
to detect diffusion alterations caused by osteoporosis but lacks diagnostic
capacities for diagnosing minor reductions of the bone mineral density detected
by DXA.
PMID- 27492215
TI - From Krebs to clinic: glutamine metabolism to cancer therapy.
AB - The resurgence of research into cancer metabolism has recently broadened
interests beyond glucose and the Warburg effect to other nutrients, including
glutamine. Because oncogenic alterations of metabolism render cancer cells
addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be
exploited for therapeutic purposes. In this Review, we provide an updated
overview of glutamine metabolism and its involvement in tumorigenesis in vitro
and in vivo, and explore the recent potential applications of basic science
discoveries in the clinical setting.
PMID- 27492221
TI - Editor's Highlight: Evaluation of a Microelectrode Array-Based Assay for Neural
Network Ontogeny Using Training Set Chemicals.
AB - Thousands of compounds in the environment have not been characterized for
developmental neurotoxicity (DNT) hazard. To address this issue, methods to
screen compounds rapidly for DNT hazard evaluation are necessary and are being
developed for key neurodevelopmental processes. In order to develop an assay for
network formation, this study evaluated effects of a training set of chemicals on
network ontogeny by measuring spontaneous electrical activity in neural networks
grown on microelectrode arrays (MEAs). Rat (0-24 h old) primary cortical cells
were plated in 48 well-MEA plates and exposed to 6 compounds: acetaminophen,
bisindolylmaleimide-1 (Bis-1), domoic acid, mevastatin, sodium orthovanadate, and
loperamide for a period of 12 days. Spontaneous network activity was recorded on
days 2, 5, 7, 9, and 12 and viability was assessed using the Cell Titer Blue
assay on day 12. Network activity (e.g. mean firing rate [MFR], burst rate [BR],
etc), increased between days 5 and 12. Random Forest analysis indicated that
across all compounds and times, temporal correlation of firing patterns (r), MFR,
BR, number of active electrodes and % of spikes in a burst were the most
influential parameters in separating control from treated wells. All compounds
except acetaminophen (<= 30 uM) caused concentration-related effects on one or
more of these parameters. Domoic acid and sodium orthovanadate altered several of
these parameters in the absence of cytotoxicity. Although cytotoxicity was
observed with Bis1, mevastatin, and loperamide, some parameters were affected by
these compounds at concentrations below those resulting in cytotoxicity. These
results demonstrate that this assay may be suitable for screening of compounds
for DNT hazard identification.
PMID- 27492222
TI - Effect of Repeated Daily Dosing with 2,4-Dinitrochlorobenzene on Glutathione
Biosynthesis and Nrf2 Activation in Reconstructed Human Epidermis.
AB - Glutathione (GSH) plays a major role in skin detoxification processes due to its
ability to conjugate electrophilic exogenous compounds with, and sometimes
without, catalysis by glutathione-s-transferase (GST). GST activity has been
demonstrated both in skin and in most in vitro skin equivalents but so far
studies have focussed on chemical clearance (conjugate identification and rate of
conjugation) and did not consider the GSH lifecycle (conjugation, recycling,
synthesis). We used the model skin sensitizer 2,4-dinitrochlorobenzene (DNCB) to
investigate the effects of chemical exposure on GSH lifecycle in reconstructed
human epidermis (RHE). We demonstrated that the RHE model is suitable to carry
out repeated cycles of 2-h exposure to DNCB over a 3-day period. After each
exposure to DNCB, the level of GSH is diminished in a dose dependent manner.
After a 22-h recovery period, GSH is replenished back to initial levels.
Accumulation of the nuclear factor E2-related factor 2 (Nrf2) in the cytosol also
occurs within the 2 h of exposure to DNCB but returns to baseline during each
recovery period, demonstrating that activation of the Nrf2 signaling pathway
offers a rapid response to chemical stress. The amount of dinitrophenyl
glutathione (DNP-SG) formed with DNCB (1) increased between the first and second
exposure and (2) reached a plateau between the second and third exposure.
Collectively, these data suggest that the metabolic capacity of skin may not be
fixed in time but defence mechanisms might be activated in response to exposure
to exogenous compounds, resulting in their accelerated clearance.
PMID- 27492223
TI - Dietary Route of Exposure for Rabbit Developmental Toxicity Studies.
AB - Dietary administration is a relevant route of oral exposure for regulatory
toxicity studies of agrochemicals as it mimics potential human intake of the
chemical via treated crops and commodities. Moreover, dietary administration of
test compounds during a developmental toxicity study can deliver a prolonged and
stable systemic exposure to the embryo or fetus at all stages of development. In
this study, strategies were employed to optimize rabbit test material consumption
via diet. Comparative toxicokinetic profiles of gavage versus dietary
administration were evaluated in pregnant or non-pregnant New Zealand White
rabbits for 2 novel agrochemicals with different plasma half-lives of elimination
(sulfoxaflor, t1/2 = 13.5 h and halauxifen, t1/2 = 1 h). Dietary administration
of sulfoxaflor resulted in stable 24-h plasma concentrations, whereas gavage
administration resulted in a 3-fold fluctuation in plasma levels between Cmax and
Cmin Dietary administration of sulfoxaflor resulted in a 2-fold higher nominal
and diurnal systemic dose when compared with gavage dosing due to Cmax-related
maternal toxicity following gavage. Results with the shorter half-life molecule,
halauxifen, were more striking with a 6-fold diurnal fluctuation by the dietary
route compared with a 368-fold fluctuation between Cmax and Cmin by gavage.
Furthermore, plasma halauxifen was detectable only up to 12 h following gavage
but up to 24 h following dietary administration. Finally, the presence of these
compounds in fetal blood samples was demonstrated, confirming that dietary
exposure is appropriate for achieving fetal exposure. Collectively, the results
of these studies support the use of dietary exposure in rabbit developmental
toxicity studies.
PMID- 27492225
TI - From the Cover: Autophagy Induction Contributes to Cadmium Toxicity in
Mesenchymal Stem Cells via AMPK/FOXO3a/BECN1 Signaling.
AB - Mesenchymal stem cells (MSCs) are a valuable in vitro model for investigating the
bone toxicity of cadmium (Cd). Autophagy has been proposed to play a pivotal role
in Cd-mediated toxicity. The FOXO family proteins are important transcription
factors that are essential to autophagy induction. This study investigated the
role of autophagy in Cd-induced skeleton damage and its potential mechanism. We
exposed MSCs to different concentrations of cadmium chloride (3.5, 7, and 14 MUM)
for 24 h. We demonstrated that Cd treatment increased autophagic flux, and
inhibition of autophagic process using BENC1 gene silencing blocked Cd-induced
cell death. Cd treatment also significantly increased mRNA levels of various
essential autophagy-related genes including ATG5, ATG12, BECN1, LC3, and ULK1.
Specifically, Cd increased FOXO3a and FOXO1 expression at the mRNA and protein
levels, and AMPK was demonstrated to enhance FOXO3a nuclear translocation and
transcriptional activity by phosphorylating FOXO3a at specific serine residues
(Ser588) in Cd-treated MSCs. Notably, knockdown of FOXO3a, but not FOXO1,
prevented autophagy-related genes expression and autophagosome formation after Cd
treatment. Taken together, our results demonstrate that Cd-induced cell death via
the overactivation of FOXO3a-dependent autophagy. Modulation of the FOXO3a
autophagy pathway may offer novel therapeutic approaches for the treatment of Cd
induced bone damage.
PMID- 27492224
TI - Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish
System.
AB - Flavonoids are a large, structurally diverse class of bioactive naturally
occurring chemicals commonly detected in breast milk, soy based infant formulas,
amniotic fluid, and fetal cord blood. The potential for pervasive early life
stage exposures raises concerns for perturbation of embryogenesis, though
developmental toxicity and bioactivity information is limited for many
flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like
chemicals using a zebrafish embryo-larval toxicity bioassay-an alternative model
for investigating developmental toxicity of environmentally relevant chemicals.
Embryos were exposed to 1-50 uM of each chemical from 6 to 120 h
postfertilization (hpf), and assessed for 26 adverse developmental endpoints at
24, 72, and 120 hpf. Behavioral changes were evaluated in morphologically normal
animals at 24 and 72 hpf, at 120 hpf using a larval photomotor response (LPR)
assay. Gene expression was comparatively evaluated for all compounds for effects
on biomarker transcripts indicative of AHR (cyp1a) and ER (cyp19a1b, esr1, lhb,
vtg) pathway bioactivity. Overall, 15 of 24 flavonoids elicited adverse effects
on one or more of the developmental or behavioral endpoints. Hierarchical
clustering and principle component analyses compared toxicity profiles and
identified 3 distinct groups of bioactive flavonoids. Despite robust induction of
multiple estrogen-responsive biomarkers, co-exposure with ER and GPER antagonists
did not ameliorate toxicity, suggesting ER-independence and alternative modes of
action. Taken together, these studies demonstrate that development is sensitive
to perturbation by bioactive flavonoids in zebrafish that are not related to
traditional estrogen receptor mode of action pathways. This integrative zebrafish
platform provides a useful framework for evaluating flavonoid developmental
toxicity and hazard prioritization.
PMID- 27492226
TI - Dietary Omega-3 Polyunsaturated Fatty Acids Prevent Vascular Dysfunction and
Attenuate Cytochrome P4501A1 Expression by 2,3,7,8-Tetrachlorodibenzo-P-Dioxin.
AB - Omega-3 polyunsaturated fatty acids (n-3 PUFAs) found in fish protect against
cardiovascular morbidity and mortality; however, many individuals avoid fish
consumption due to concerns about pollutants. We tested the hypothesis that n-3
PUFAs would prevent vascular dysfunction induced by 2,3,7,8-tetrachlorodibenzo-p
dioxin (TCDD). C57Bl/6 male mice were fed a chow or n-3 PUFA diet for 10 weeks
and were exposed to vehicle or 300 ng/kg/d TCDD during the final 2 weeks on each
diet. Aortic vasoconstriction mediated by arachidonic acid (AA) +/- SKF525 (P450
inhibitor) or SQ29548 (thromboxane/prostanoid [TP] receptor antagonist) was
assessed. RBC fatty acids and expression of n-3 and n-6 PUFA metabolites were
analyzed. Cytochrome P4501A1 (CYP1A1), CYP1B1, and aryl hydrocarbon receptor
(AHR) expression was measured. TCDD significantly increased AA-mediated
vasoconstriction on a chow diet by increasing the contribution of P450s and TP
receptor to the constriction response. In contrast, the n-3 PUFA diet prevented
the TCDD-induced increase in AA vasoconstriction and normalized the contribution
of P450s and TP receptor. Although TCDD increased the levels of AA
vasoconstrictors on the chow diet, this increase was prevent by the n-3 PUFA
diet. Additionally, the n-3 PUFA diet significantly increased the levels of n-3
PUFA-derived vasodilators and TCDD increased these levels further. Interestingly,
the n-3 PUFA diet significantly attenuated CYP1A1 induction by TCDD without a
significant effect on AHR expression. These data suggest that n-3 PUFAs can
prevent TCDD-induced vascular dysfunction by decreasing vasoconstrictors,
increasing vasodilators, and attenuating CYP1A1 induction, which has been shown
previously to contribute to TCDD-induced vascular dysfunction.
PMID- 27492228
TI - Helminth Infections and Cardiovascular Diseases: Toxocara Species is Contributing
to the Disease.
AB - Toxocariasis is the clinical term used to describe human infection with either
the dog ascarid Toxocara canis or the feline ascarid Toxocara cati. As with other
helminths zoonoses, the infective larvae of these Toxocara species cannot mature
into adults in the human host. Instead, the worms wander through organs and
tissues, mainly the liver, lungs, myocardium, kidney and central nervous system,
in a vain attempt to find that, which they need to mature into adults. The
migration of these immature nematode larvae causes local and systemic
inflammation, resulting in the "larva migrans" syndrome. The clinical
manifestations of toxocariasis are divided into visceral larva migrans, ocular
larva migrans and neurotoxocariasis. Subclinical infection is often referred to
as covert toxocariasis. One of the primary causes of death all around the world
is cardiovascular disease that accounted for up to 30 percent of all-cause
mortality. Cardiovascular disease and more precisely atherosclerotic
cardiovascular disease, is predicted to remain the single leading cause of death
(23.3 million deaths by 2030). A-quarter of people presenting the disease does
not show any of the known cardiovascular risk factors. Therefore, there is
considerable interest in looking for novel components affecting cardiovascular
health, especially for those that could improve global cardiovascular risk
prediction. This review endeavours to summarize the clinical aspects, new
diagnostic and therapeutic perspectives of toxocaral disease with cardiovascular
manifestations.
PMID- 27492227
TI - Cardiac Imaging in Heart Failure with Comorbidities.
AB - Imaging modalities stand at the frontiers for progress in congestive heart
failure (CHF) screening, risk stratification and monitoring. Advancements in
echocardiography (ECHO) and Magnetic Resonance Imaging (MRI) have allowed for
improved tissue characterizations, cardiac motion analysis, and cardiac
performance analysis under stress. Common cardiac comorbidities such as
hypertension, metabolic syndromes and chronic renal failure contribute to cardiac
remodeling, sharing similar pathophysiological mechanisms starting with
interstitial changes, structural changes and finally clinical CHF. These imaging
techniques can potentially detect changes earlier. Such information could have
clinical benefits for screening, planning preventive therapies and risk
stratifying patients. Imaging reports have often focused on traditional measures
without factoring these novel parameters. This review is aimed at providing a
synopsis on how we can use this information to assess and monitor improvements
for CHF with comorbidities.
PMID- 27492230
TI - Coccidioidomycosis in Patients with Selected Solid Organ Cancers: A Case Series
and Review of Medical Literature.
AB - Coccidioidomycosis is a common infection in the desert southwestern USA;
approximately 3 % of healthy persons in Arizona alone become infected annually.
Coccidioidomycosis may be severe in immunocompromised persons, but experience
among patients with solid organ cancer has not been fully described. Therefore,
we aimed to describe the clinical courses of patients whose cancers were
complicated by coccidioidomycosis at our institution, which is located in an area
with endemic Coccidioides. To do so, we conducted a retrospective review from
January 1, 2000, through December 31, 2014, of all patients with breast,
colorectal, or ovarian cancer whose cancer courses were complicated by
coccidioidomycosis. We identified 17,576 cancer patients; 14 (0.08 %) of these
patients met criteria for proven or probable coccidioidomycosis diagnosed within
the first 2 years after the cancer diagnosis. All of these patients had primary
pulmonary coccidioidomycosis, none had relapsed prior infection, and 1 had
possible extrapulmonary dissemination. Five had active coccidioidal infection
during chemotherapy, 1 of whom was hospitalized for coccidioidal pneumonia. All
were treated with fluconazole, and all improved clinically. Eleven did not
require prolonged courses of fluconazole. There were no clearly demonstrated
episodes of relapsed infection. In conclusion, coccidioidomycosis was not a
common complication of breast, colorectal, or ovarian cancers in patients treated
at our institution, and it was not commonly complicated by severe or disseminated
infection.
PMID- 27492229
TI - Imaging Subclinical Atherosclerosis: Where Do We Stand?
AB - The age of initiation and the rate of progression of atherosclerosis vary
markedly among individuals and have been difficult to predict with traditional
cardiovascular risk assessment models. Although these risk models provide good
discrimination and calibration in certain populations, cardiovascular disease
(CVD) risk may not be accurately estimated in low- and intermediate risk
individuals. Therefore, imaging techniques such as Ankle-Brachial Index (ABI),
Coronary Artery Calcium score (CAC), carotid Intima-Media Thickness (cIMT), flow
mediated dilation (FMD) and Positron Emission Tomography (PET) have been
developed and used to reclassify these individuals. In the present article we
review the role of the most commonly used imaging techniques for CVD risk
assessment.
PMID- 27492231
TI - SEX-DETector: A Probabilistic Approach to Study Sex Chromosomes in Non-Model
Organisms.
AB - We propose a probabilistic framework to infer autosomal and sex-linked genes from
RNA-seq data of a cross for any sex chromosome type (XY, ZW, and UV). Sex
chromosomes (especially the non-recombining and repeat-dense Y, W, U, and V) are
notoriously difficult to sequence. Strategies have been developed to obtain
partially assembled sex chromosome sequences. Most of them remain difficult to
apply to numerous non-model organisms, either because they require a reference
genome, or because they are designed for evolutionarily old systems. Sequencing a
cross (parents and progeny) by RNA-seq to study the segregation of alleles and
infer sex-linked genes is a cost-efficient strategy, which also provides
expression level estimates. However, the lack of a proper statistical framework
has limited a broader application of this approach. Tests on empirical Silene
data show that our method identifies 20-35% more sex-linked genes than existing
pipelines, while making reliable inferences for downstream analyses.
Approximately 12 individuals are needed for optimal results based on simulations.
For species with an unknown sex-determination system, the method can assess the
presence and type (XY vs. ZW) of sex chromosomes through a model comparison
strategy. The method is particularly well optimized for sex chromosomes of young
or intermediate age, which are expected in thousands of yet unstudied lineages.
Any organisms, including non-model ones for which nothing is known a priori, that
can be bred in the lab, are suitable for our method. SEX-DETector and its
implementation in a Galaxy workflow are made freely available.
PMID- 27492232
TI - Predictive Models of Recombination Rate Variation across the Drosophila
melanogaster Genome.
AB - In all eukaryotic species examined, meiotic recombination, and crossovers in
particular, occur non-randomly along chromosomes. The cause for this non-random
distribution remains poorly understood but some specific DNA sequence motifs have
been shown to be enriched near crossover hotspots in a number of species. We
present analyses using machine learning algorithms to investigate whether DNA
motif distribution across the genome can be used to predict crossover variation
in Drosophila melanogaster, a species without hotspots. Our study exposes a
combinatorial non-linear influence of motif presence able to account for a
significant fraction of the genome-wide variation in crossover rates at all
genomic scales investigated, from 20% at 5-kb to almost 70% at 2,500-kb scale.
The models are particularly predictive for regions with the highest and lowest
crossover rates and remain highly informative after removing sub-telomeric and
centromeric regions known to have strongly reduced crossover rates.
Transcriptional activity during early meiosis and differences in motif use
between autosomes and the X chromosome add to the predictive power of the models.
Moreover, we show that population-specific differences in crossover rates can be
partly explained by differences in motif presence. Our results suggest that
crossover distribution in Drosophila is influenced by both meiosis-specific
chromatin dynamics and very local constitutive open chromatin associated with DNA
motifs that prevent nucleosome stabilization. These findings provide new
information on the genetic factors influencing variation in recombination rates
and a baseline to study epigenetic mechanisms responsible for plastic
recombination as response to different biotic and abiotic conditions and
stresses.
PMID- 27492233
TI - A Genome-Scale Investigation of How Sequence, Function, and Tree-Based Gene
Properties Influence Phylogenetic Inference.
AB - Molecular phylogenetic inference is inherently dependent on choices in both
methodology and data. Many insightful studies have shown how choices in
methodology, such as the model of sequence evolution or optimality criterion
used, can strongly influence inference. In contrast, much less is known about the
impact of choices in the properties of the data, typically genes, on phylogenetic
inference. We investigated the relationships between 52 gene properties (24
sequence-based, 19 function-based, and 9 tree-based) with each other and with
three measures of phylogenetic signal in two assembled data sets of 2,832 yeast
and 2,002 mammalian genes. We found that most gene properties, such as
evolutionary rate (measured through the percent average of pairwise identity
across taxa) and total tree length, were highly correlated with each other.
Similarly, several gene properties, such as gene alignment length, Guanine
Cytosine content, and the proportion of tree distance on internal branches
divided by relative composition variability (treeness/RCV), were strongly
correlated with phylogenetic signal. Analysis of partial correlations between
gene properties and phylogenetic signal in which gene evolutionary rate and
alignment length were simultaneously controlled, showed similar patterns of
correlations, albeit weaker in strength. Examination of the relative importance
of each gene property on phylogenetic signal identified gene alignment length,
alongside with number of parsimony-informative sites and variable sites, as the
most important predictors. Interestingly, the subsets of gene properties that
optimally predicted phylogenetic signal differed considerably across our three
phylogenetic measures and two data sets; however, gene alignment length and RCV
were consistently included as predictors of all three phylogenetic measures in
both yeasts and mammals. These results suggest that a handful of sequence-based
gene properties are reliable predictors of phylogenetic signal and could be
useful in guiding the choice of phylogenetic markers.
PMID- 27492234
TI - Convergent Evolution of Fern-Specific Mitochondrial Group II Intron atp1i361g2
and Its Ancient Source Paralogue rps3i249g2 and Independent Losses of Intron and
RNA Editing among Pteridaceae.
AB - Mitochondrial intron patterns are highly divergent between the major land plant
clades. An intron in the atp1 gene, atp1i361g2, is an example for a group II
intron specific to monilophytes (ferns). Here, we report that atp1i361g2 is lost
independently at least 4 times in the fern family Pteridaceae. Such plant
organelle intron losses have previously been found to be accompanied by loss of
RNA editing sites in the flanking exon regions as a consequence of genomic
recombination of mature cDNA. Instead, we now observe that RNA editing events in
both directions of pyrimidine exchange (C-to-U and U-to-C) are retained in atp1
exons after loss of the intron in Pteris argyraea/biaurita and in Actiniopteris
and Onychium We find that atp1i361g2 has significant similarity with intron
rps3i249g2 present in lycophytes and gymnosperms, which we now also find highly
conserved in ferns. We conclude that atp1i361g2 may have originated from the more
ancestral rps3i249g2 paralogue by a reverse splicing copy event early in the
evolution of monilophytes. Secondary structure elements of the two introns, most
characteristically their domains III, show strikingly convergent evolution in the
monilophytes. Moreover, the intron paralogue rps3i249g2 reveals relaxed evolution
in taxa where the atp1i361g2 paralogue is lost. Our findings may reflect
convergent evolution of the two related mitochondrial introns exerted by co
evolution with an intron-binding protein simultaneously acting on the two
paralogues.
PMID- 27492236
TI - Binding Kinetics in Drug Discovery.
AB - Over the last years, researchers have increasingly become interested in measuring
and understanding drugs' binding kinetics, namely the time in which drug and its
target associate and dissociate. Historically, drug discovery programs focused on
the optimization of target affinity as a proxy of in-vivo efficacy. However,
often the efficacy of a ligand is not appropriately described by the in-vitro
measured drug-receptor affinity, but rather depends on the lifetime of the in
vivo drug-receptor interaction. In this review we review recent works that
highlight the importance of binding kinetics, molecular determinants for rational
optimization and the recent emergence of computational methods as powerful tools
in measuring and understanding binding kinetics.
PMID- 27492235
TI - Regular Higher Order Repeat Structures in Beetle Tribolium castaneum Genome.
AB - Higher order repeats (HORs) containing tandems of primary and secondary repeat
units (head-to-tail "tandem within tandem pattern"), referred to as regular HORs,
are typical for primate alpha satellite DNAs and most pronounced in human genome.
Regular HORs are known to be a result of recent evolutionary processes. In non
primate genomes mostly so called complex HORs have been found, without head to
tail tandem of primary repeat units. In beetle Tribolium castaneum, considered as
a model case for genome studies, large tandem repeats have been identified, but
no HORs have been reported. Here, using our novel robust repeat finding algorithm
Global Repeat Map, we discover two regular and six complex HORs in T. castaneum.
In organizational pattern, the integrity and homogeneity of regular HORs in T.
castaneum resemble human regular HORs (with T. castaneum monomers different from
human alpha satellite monomers), involving a wider range of monomer lengths than
in human HORs. Similar regular higher order repeat structures have previously not
been found in insects. Some of these novel HORs in T. castaneum appear as most
regular among known HORs in non-primate genomes, although with substantial
riddling. This is intriguing, in particular from the point of view of role of non
coding repeats in modulation of gene expression.
PMID- 27492237
TI - In silico Exploration of the Conformational Universe of GPCRs.
AB - The structural plasticity of G protein coupled receptors (GPCRs) leads to a
conformational universe going from inactive to active receptor states with
several intermediate states. Many of them have not been captured yet and their
role for GPCR activation is not well understood. The study of this conformational
space and the transition dynamics between different receptor populations is a
major challenge in molecular biophysics. The rational design of effector
molecules that target such receptor populations allows fine-tuning receptor
signalling with higher specificity to produce drugs with safer therapeutic
profiles. In this minireview, we outline highly conserved receptor regions which
are considered determinant for the establishment of distinct receptor states. We
then discuss in-silico approaches such as dimensionality reduction methods and
Markov State Models to explore the GPCR conformational universe and exploit the
obtained conformations through structure-based drug design.
PMID- 27492238
TI - Constructing and Validating 3D-pharmacophore Models to a Set of MMP-9 Inhibitors
for Designing Novel Anti-melanoma Agents.
AB - A receptor-independent (RI) four-dimensional structure-activity relationship (4D
QSAR) formalism was applied to a set of sixty-four beta-N-biaryl ether
sulfonamide hydroxamate derivatives, previously reported as potent inhibitors
against matrix metalloproteinase subtype 9 (MMP-9). MMP-9 belongs to a group of
enzymes related to the cleavage of several extracellular matrix components and
has been associated to cancer invasiveness/metastasis. The best RI 4D-QSAR model
was statistically significant (N=47; r(2) =0.91; q(2) =0.83; LSE=0.09; LOF=0.35;
outliers=0). Leave-N-out (LNO) and y-randomization approaches indicated the QSAR
model was robust and presented no chance correlation, respectively. Furthermore,
it also had good external predictability (82 %) regarding the test set (N=17). In
addition, the grid cell occupancy descriptors (GCOD) of the predicted bioactive
conformation for the most potent inhibitor were successfully interpreted when
docked into the MMP-9 active site. The 3D-pharmacophore findings were used to
predict novel ligands and exploit the MMP-9 calculated binding affinity through
molecular docking procedure.
PMID- 27492239
TI - In silico and in vitro Studies on Begomovirus Induced Andrographolide
Biosynthesis Pathway in Andrographis Paniculata for Combating Inflammation and
Cancer.
AB - Andrographolide and neoandrographolide are major bioactive molecules of
Andrographis paniculata, a well-known medicinal plant. These molecules exhibited
varying degrees of anti-inflammatory and anticancer activities in-vitro and in
vivo. Role of begomovirus protein C2/TrAP in biosynthesis of andrographolide was
identified through molecular modeling, docking and predicted results were
substantiated by in vitro studies. Homology molecular modeling and molecular
docking were performed to study the binding conformations and different bonding
behaviors, in order to reveal the possible mechanism of action behind higher
accumulation of andrographolide. It was concluded that C2/TrAP inhibit the
activation of SNF1-Related Protein Kinase-1 (SnRK1) in terpenoid pathway and
removes the negative regulation of 3-hydroxy-3-methylglutaryl-CoA reductase
(HMGR) by SnRK1, leading to higher accumulation of andrographolide and
neoandrographolide in begomovirus infected plants. The binding site residues of
SnRK1 docked with C2/TrAP were found to be associated with ATP binding site,
substrate binding site and activation loop. Predicted results were also validated
by HPTLC. This study provides important insights into understanding the role of
viral protein in altering the regulation of biosynthesis of andrographolide and
could be used in future research to develop biomimetic methods for increasing the
production of such phytometabolites having anti-cancerous and anti-inflammatory
properties.
PMID- 27492240
TI - Derivation of Self-inhibitory Helical Peptides to Target Rho-kinase Dimerization
in Cerebrovascular Malformation: Structural Bioinformatics Analysis and Peptide
Binding Assay.
AB - Rho-kinase dimerization is essential for its kinase activity and biological
function; disruption of the dimerization has recently been established as a new
and promising therapeutics strategy for cerebrovascular malformation (CM). Based
on Rho-kinase dimer crystal structure we herein combined in silico analysis and
in vitro assay to rationally derive self-inhibitory peptides from the
dimerization interface. Three peptides namely Hlp1, Hlp2 and Hlp3 were
successfully designed that have potential capability to rebind at the
dimerization domain of Rho-kinase. Molecular dynamics (MD) simulations revealed
that these peptides are helically structured when bound to Rho-kinase, but
exhibit partially intrinsic disorder in unbound state. Binding free energy (BFE)
analysis suggested that the peptides have a satisfactory energetic profile to
interact with Rho-kinase. The computational findings were then substantiated by
fluorescence anisotropy assays, conforming that the helical peptides can bind
tightly to Rho-kinase with affinity KD at micromolar level. These designed
peptides are considered as lead molecular entities that can be further modified
and optimized to obtain more potent peptidomimetics as self-competitors to
disrupt Rho-kinase dimerization in CM.
PMID- 27492241
TI - Interaction of Tenebrio Molitor Antifreeze Protein with Ice Crystal: Insights
from Molecular Dynamics Simulations.
AB - Antifreeze proteins (AFP) observed in cold-adapting organisms bind to ice
crystals and prevent further ice growth. However, the molecular mechanism of AFP
ice binding and AFP-inhibited ice growth remains unclear. Here we report the
interaction of the insect antifreeze protein (Tenebrio molitor, TmAFP) with ice
crystal by molecular dynamics simulation studies. Two sets of simulations were
carried out at 263 K by placing the protein near the primary prism plane (PP) and
basal plane (BL) of the ice crystal. To delineate the effect of temperatures,
both the PP and BL simulations were carried out at 253 K as well. The analyses
revealed that the protein interacts strongly with the ice crystal in BL
simulation than in PP simulation both at 263 K and 253 K. Further, it was
observed that the interactions are primarily mediated through the interface
waters. We also observed that as the temperature decreases, the interaction
between the protein and the ice increases which can be attributed to the
decreased flexibility and the increased structuring of the protein at low
temperature. In essence, our study has shed light on the interaction mechanism
between the TmAFP antifreeze protein and the ice crystal.
PMID- 27492242
TI - Docking-based Design of Galantamine Derivatives with Dual-site Binding to
Acetylcholinesterase.
AB - The enzyme acetylcholinesterase is a key target in the treatment of Alzheimer's
disease because of its ability to hydrolyze acetylcholine via the catalytic
binding site and to accelerate the aggregation of amyloid-beta peptide via the
peripheral anionic site (PAS). Using docking-based predictions, in the present
study we design 20 novel galantamine derivatives with alkylamide spacers of
different length ending with aromatic fragments. The galantamine moiety blocks
the catalytic site, while the terminal aromatic fragments bind in PAS. The best
predicted compounds are synthesized and tested for acetylcholinesterase
inhibitory activity. The experimental results confirm the predictions and show
that the heptylamide spacer is of optimal length to bridge the galantamine moiety
bound in the catalytic site and the aromatic fragments interacting with PAS.
Among the tested terminal aromatic fragments, the phenethyl substituent is the
most suitable for binding in PAS.
PMID- 27492243
TI - Guided Iterative Substructure Search (GI-SSS) - A New Trick for an Old Dog.
AB - Substructure search (SSS) is a fundamental technique supported by various
chemical information systems. Many users apply it in an iterative manner: they
modify their queries to shape the composition of the retrieved hit sets according
to their needs. We propose and evaluate two heuristic extensions of SSS aimed at
simplifying these iterative query modifications by collecting additional
information during query processing and visualizing this information in an
intuitive way. This gives the user a convenient feedback on how certain changes
to the query would affect the retrieved hit set and reduces the number of trial
and-error cycles needed to generate an optimal search result. The proposed
heuristics are simple, yet surprisingly effective and can be easily added to
existing SSS implementations.
PMID- 27492244
TI - Breast cancer biologic and etiologic heterogeneity by young age and menopausal
status in the Carolina Breast Cancer Study: a case-control study.
AB - BACKGROUND: Young-onset breast cancer (<40 years) is associated with worse
prognosis and higher mortality. Breast cancer risk factors may contribute to
distinct tumor biology and distinct age at onset, but understanding of these
relationships has been hampered by limited representation of young women in
epidemiologic studies and may be confounded by menopausal status. METHODS: We
examined tumor characteristics and epidemiologic risk factors associated with
premenopausal women's and young women's breast cancer in phases I-III of the
Carolina Breast Cancer Study (5309 cases, 2022 control subjects). Unconditional
logistic regression was used to assess heterogeneity by age (<40 vs. >=40 years)
and menopausal status. RESULTS: In both premenopausal and postmenopausal strata,
younger women had more aggressive disease, including higher stage, hormone
receptor-negative, disease as well as increased frequency of basal-like subtypes,
lymph node positivity, and larger tumors. Higher waist-to-hip ratio was
associated with reduced breast cancer risk among young women but with elevated
risk among older women. Parity was associated with increased risk among young
women and reduced risk among older women, while breastfeeding was more strongly
protective for young women. Longer time since last birth was protective for older
women but not for young women. In comparison, when we stratified by age,
menopausal status was not associated with distinct risk factor or tumor
characteristic profiles, except for progesterone receptor status, which was more
commonly positive among premenopausal women. CONCLUSIONS: Age is a key predictor
of breast cancer biologic and etiologic heterogeneity and may be a stronger
determinant of heterogeneity than menopausal status. Young women's breast cancer
appears to be etiologically and biologically distinct from that among older
women.
PMID- 27492245
TI - The potential role of biomarkers in predicting gestational diabetes.
AB - Gestational diabetes (GD) is a frequent complication during pregnancy and is
associated with maternal and neonatal complications. It is suggested that a
disturbing environment for the foetus, such as impaired glucose metabolism during
intrauterine life, may result in enduring epigenetic changes leading to increased
disease risk in adult life. Hence, early prediction of GD is vital. Current risk
prediction models are based on maternal and clinical parameters, lacking a strong
predictive value. Adipokines are mainly produced by adipocytes and suggested to
be a link between obesity and its cardiovascular complications. Various
adipokines, including adiponectin, leptin and TNF&, have shown to be dysregulated
in GD. This review aims to outline biomarkers potentially associated with the
pathophysiology of GD and discuss the role of integrating predictive biomarkers
in current clinical risk prediction models, in order to enhance the
identification of those at risk.
PMID- 27492246
TI - Characterization of gonadotropic cells during continuous and seasonal
spermatogenesis of two freshwater fish species: a histochemical and
immunohistochemical study.
AB - This work describes gonadotropic (GtH) cells and their morphological and
immunohistochemical changes during the spermatogenic cycle of Serrasalmus
maculatus (continuous spermatogenesis) and Pimelodus maculatus (seasonal
spermatogenesis). GtH cells, widely distributed in the proximal pars distalis of
the adenohypophysis, were characterized as round-shaped cells with eccentric
nucleus, and cytoplasm with basophilic secretory granules and a variable number
of vacuoles for both species. Immunohistochemistry against beta-follicle
stimulating hormone (Fsh) and beta-luteinizing hormone (Lh) in adjacent sections
showed two separated GtH-producing cell populations, and a third population where
both GtHs are expressed in the same cell for both species. In the seasonal
spermatogenesis of P. maculatus, GtH cells seemed to be more abundant during
developing and spawning capable phases. In contrast, no cyclic changes were
detected in the continuous spermatogenesis of S. maculatus, except for the strong
immunoreaction for Fsh and Lh in males with intense spermiogenesis. We conclude
that changes reported here might reflect the type of spermatogenic cycle
(seasonal or continuous) which are under different regulatory mechanisms
(environmental and internal cues) controlling the reproduction in these species.
PMID- 27492247
TI - Within and beyond the communal turn to informed consent in industry-sponsored
pharmacogenetics research: merits and challenges of community advisory boards.
AB - The one-size-fits-all paradigm of drug development fails to address inter
individual variability in drug response. Pharmacogenetics research aims at
studying the role of genotypic differences in drug response. Recently, the
pharmaceutical industry has shown interest to embed pharmacogenetics studies in
the process of drug development. Nevertheless, population-based and commercial
aspects of such future-oriented studies pose challenges for individually based
informed consent (IC). As an exemplar of the communal turn to IC procedures,
community advisory boards (CABs) have been integrated into different types of
medical research. CABs hold the promise of organizing the relationship between
participants and researchers in a more reciprocal and participatory way, offering
possible means of overcoming the lapses of individualistic IC. However, the
involvement of CABs with pharmacogenetics research might be rife with
difficulties, uncertainties, and challenges. The current study first reviews the
existing literature to discuss added values and challenges of relying on CABs as
a supplement to individually based IC. Then, the particular moral and regulatory
landscape of pharmacogenetics research will be delineated to argue that community
engagement is both necessary and promising beyond the communal turn to IC
processes. Three main features of the landscape include (1) new supportive
stances that some regulatory bodies have adopted toward pharmacogenetics
research, (2) the motivation of the industry to draw reception and trust from the
subpopulations, and (3) the important role of the society in generating and
embedding pharmacogenetics knowledge. Finally, some points to consider will be
discussed to contextualize relying on CABs within this landscape.
PMID- 27492248
TI - Delayed upper tract drainage on voiding cystourethrogram may not be associated
with increased risk of urinary tract infection in children with vesicoureteral
reflux.
AB - INTRODUCTION: Urinary stasis in the setting of obstruction provides an
opportunistic environment for bacterial multiplication and is a well-established
risk factor for UTI. Vesicoureteral reflux (VUR) with delayed upper tract
drainage (UTD) on VCUG has been reported to correlate with increased UTI risk. We
sought to determine whether delayed UTD can be reliably classified, and whether
it correlates with UTI incidence, VCUG, or endoscopic findings. METHODS: Children
undergoing endoscopic surgery for primary VUR (2009-2012) were identified. VUR
grade, timing, and laterality were abstracted. Demographics, hydrodistention (HD)
grade, reported febrile and culture-proven UTI were assessed. UTD on VCUG was
graded on post-void images as 1 = partial/complete UTD or 2 = no/increased UTD.
Inter-observer agreement was calculated. Patients were excluded for incomplete
imaging or inability to void during VCUG. RESULTS: The cohort included 128
patients (10M, 118F), mean age 4.1 +/- 2.1 years. Mean age at diagnosis was 2.8
+/- 2.8 years. Mean maximum VUR grade was 3 +/- 0.9: 1 (7.8%), 2 (20.3%), 3
(43%), 4 (25.8%), 5 (3.1%). UTD occurred in 45 (35%), and no drainage in 83 (65%)
patients. Agreement coefficient between graders was 0.596 (p < 0.0001). Cultures
were available in 100 patients (70 positive). Patients experienced a mean of 2 +/
1.2 parent-reported fUTIs and 1.2 +/- 1.2 culture-proven UTIs from birth to
surgery. UTI rate did not differ by UTD status for parent or culture-proven UTI
(Table). On multivariate analysis, no patient characteristic was a significant
predictor of UTI based on drainage status. Children diagnosed with VUR before 1
year of age had a higher verified UTI rate (p < 0.001). However, drainage was not
a significant predictor of UTI rate and when testing the interaction of drainage
and age. CONCLUSION: We sought to determine whether UTD was an accurate predictor
of UTI risk to maximize available prognostic information from a single VCUG.
Delayed UTD was not a predictor of infection in our patients, nor was it
associated with previously described UTI risk factors, such as VUR timing or
grade, and voiding dysfunction. Limitations included the retrospective nature of
the study in patients undergoing endoscopic VUR treatment, and possible
inaccurate UTI reports from parents and pediatricians. UTD can be reliably scored
using a binary system with high inter-observer correlation. Our data call into
question the previous finding that children with poor UTD are at increased risk
of recurrent UTI. Delayed UTD is also not associated with higher HD, or VUR grade
compared with those with more prompt UTD.
PMID- 27492249
TI - Corrigendum to "Development of a DNA-based microarray for the detection of
zoonotic pathogens in rodent species" [Mol. Cell. Probes 29 (6) (2015)].
PMID- 27492251
TI - Repeated movie viewings produce similar local activity patterns but different
network configurations.
AB - People seek novelty in everyday life, but they also enjoy viewing the same movies
or reading the same novels a second time. What changes and what stays the same
when re-experiencing a narrative? In examining this question with functional
neuroimaging, we found that brain activity reorganizes in a hybrid, scale
dependent manner when individuals processed the same audiovisual narrative a
second time. At the most local level, sensory systems (occipital and temporal
cortices) maintained a similar temporal activation profile during the two
viewings. Nonetheless, functional connectivity between these same lateral
temporal regions and other brain regions was stronger during the second viewing.
Furthermore, at the level of whole-brain connectivity, we found a significant
rearrangement of network partition structure: lateral temporal and inferior
frontal regions clustered together during the first viewing but merged within a
fronto-parietal cluster in the second. Our findings show that repetition
maintains local activity profiles. However, at the same time, it is associated
with multiple network-level connectivity changes on larger scales, with these
changes strongly involving regions considered core to language processing.
PMID- 27492250
TI - Role of thrombospondin 1 in liver diseases.
AB - Thrombospondin 1 (TSP1) is a matricellular glycoprotein that can be secreted by
many cell types. Through binding to extracellular proteins and/or cell surface
receptors, TSP1 modulates a variety of cellular functions. Since its discovery in
1971, TSP1 has been found to play important roles in multiple biological
processes including angiogenesis, apoptosis, latent transforming growth factor
beta activation, and immune regulation. Thrombospondin 1 is also involved in
regulating many organ functions. However, the role of TSP1 in liver diseases has
not been extensively addressed. In this review, we summarize the findings about
the possible role that TSP1 plays in chronic liver diseases focusing on non
alcoholic fatty liver diseases, liver fibrosis, and hepatocellular carcinoma.
PMID- 27492252
TI - Glycoluril-Derived Molecular Clips are Potent and Selective Receptors for
Cationic Dyes in Water.
AB - Molecular clip 1 remains monomeric in water and engages in host-guest recognition
processes with suitable guests. We report the Ka values for 32 1?guest complexes
measured by 1 H NMR, UV/Vis, and fluorescence titrations. The cavity of 1 is
shaped by aromatic surfaces of negative electrostatic potential and therefore
displays high affinity and selectivity for planar and cationic aromatic guests
that distinguishes it from CB[n] receptors that prefer aliphatic over aromatic
guests. Electrostatic effects play a dominant role in the recognition process
whereby ion-dipole interactions may occur between ammonium ions and the C=O
groups of 1, between the SO3- groups of 1 and pendant cationic groups on the
guest, and within the cavity of 1 by cation-pi interactions. Host 1 displays a
high affinity toward dicationic guests with large planar aromatic surfaces (e.g.
naphthalene diimide NDI+ and perylene diimide PDI+) and cationic dyes derived
from acridine (e.g. methylene blue and azure A). The critical importance of
cation-pi interactions was ascertained by a comparison of analogous neutral and
cationic guests (e.g. methylene violet vs. methylene blue; quinoline vs. N
methylquinolinium; acridine vs. N-methylacridinium; neutral red vs. neutral red
H+ ) the affinities of which differ by up to 380-fold. We demonstrate that the
high affinity of 1 toward methylene blue (Ka =3.92*107 m-1 ; Kd =25 nm) allows
for the selective sequestration and destaining of U87 cells stained with
methylene blue.
PMID- 27492253
TI - Targeting Splicing in the Treatment of Myelodysplastic Syndromes and Other
Myeloid Neoplasms.
AB - Genome sequencing of primary cells from patients with myelodysplastic syndromes
(MDS) led to the identification of recurrent heterozygous mutations in gene
encoding components of the spliceosome, the cellular machinery which processes
pre-messenger RNA (mRNA) to mature mRNA during gene transcription. Splicing
mutations are mutually exclusive with one another and collectively represent the
most common mutation class in MDS, occurring in approximately 60 % of patients
overall and more than 80 % of those with ring sideroblasts. Evidence from animal
models suggests that homozygous splicing mutations are lethal, and that in
heterozygously mutated models, any further disruption of splicing triggers
apoptosis and cell death. MDS cells with spliceosome mutations are thus uniquely
vulnerable to therapies targeting splicing, which may be tolerated by healthy
cells. The spliceosome is emerging as a novel therapeutic target in MDS and
related myeloid neoplasms, with the first clinical trial of a splicing modulator
opening in 2016.
PMID- 27492254
TI - Microfluidics: a transformational tool for nanomedicine development and
production.
AB - Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids
at the nanoliter scale. The ability to control the mixing of fluids and the
continuous nature of the process make it apt for solvent/antisolvent
precipitation of drug-delivery nanoparticles. This review describes the use of
numerous microfluidic designs for the formulation and production of lipid
nanoparticles, liposomes and polymer nanoparticles to encapsulate and deliver
small molecule or genetic payloads. The advantages of microfluidics are
illustrated through examples from literature comparing conventional processes
such as beaker and T-tube mixing to microfluidic approaches. Particular emphasis
is placed on examples of microfluidic nanoparticle formulations that have been
tested in vitro and in vivo. Fine control of process parameters afforded by
microfluidics, allows unprecedented optimization of nanoparticle quality and
encapsulation efficiency. Automation improves the reproducibility and
optimization of formulations. Furthermore, the continuous nature of the
microfluidic process is inherently scalable, allowing optimization at low
volumes, which is advantageous with scarce or costly materials, as well as scale
up through process parallelization. Given these advantages, microfluidics is
poised to become the new paradigm for nanomedicine formulation and production.
PMID- 27492255
TI - Stromal Hedgehog signalling is downregulated in colon cancer and its restoration
restrains tumour growth.
AB - A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC)
has been proposed. In CRC and other solid tumours, Hh ligands are upregulated;
however, a specific Hh antagonist provided no benefit in a clinical trial. Here
we use Hh reporter mice to show that downstream Hh activity is unexpectedly
diminished in a mouse model of colitis-associated colon cancer, and that
downstream Hh signalling is restricted to the stroma. Functionally, stroma
specific Hh activation in mice markedly reduces the tumour load and blocks
progression of advanced neoplasms, partly via the modulation of BMP signalling
and restriction of the colonic stem cell signature. By contrast, attenuated Hh
signalling accelerates colonic tumourigenesis. In human CRC, downstream Hh
activity is similarly reduced and canonical Hh signalling remains predominantly
paracrine. Our results suggest that diminished downstream Hh signalling enhances
CRC development, and that stromal Hh activation can act as a colonic tumour
suppressor.
PMID- 27492256
TI - Distinct splicing signatures affect converged pathways in myelodysplastic
syndrome patients carrying mutations in different splicing regulators.
AB - Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders with
prevalent mutations in several splicing factors, but the splicing programs linked
to specific mutations or MDS in general remain to be systematically defined. We
applied RASL-seq, a sensitive and cost-effective platform, to interrogate 5502
annotated splicing events in 169 samples from MDS patients or healthy
individuals. We found that splicing signatures associated with normal
hematopoietic lineages are largely related to cell signaling and differentiation
programs, whereas MDS-linked signatures are primarily involved in cell cycle
control and DNA damage responses. Despite the shared roles of affected splicing
factors in the 3' splice site definition, mutations in U2AF1, SRSF2, and SF3B1
affect divergent splicing programs, and interestingly, the affected genes fall
into converging cancer-related pathways. A risk score derived from 11 splicing
events appears to be independently associated with an MDS prognosis and AML
transformation, suggesting potential clinical relevance of altered splicing
patterns in MDS.
PMID- 27492258
TI - Aldo-X Bifunctional Building Blocks for the Synthesis of Heterocycles.
AB - Compounds containing oxygen, nitrogen, or sulfur atoms inside the rings are
attracting much attention and interest due to their biological importance. In
recent years, several methods for the synthesis of such molecules have been
reported by using aldo-X bifunctional building blocks (AXB3 s) as substrates;
these are a wide class of organic molecules that contain at least two reactive
sites, among them, one aldehyde, acetal, or semiacetal group was involved.
Because of the multiple reactivities, AXB3 s are widely used in the one-pot
synthesis of biologically important heterocycles. This review summarizes the
synthesis of important heterocycles by using AXB3 s as pivotal components in
establishing multicomponent reactions, tandem reactions, and so forth. In many
cases, the established reaction systems with AXB3 s were characterized by some
green properties, such as easy access to the substrate, mild and environmentally
benign conditions, and wide scope of the substrate.
PMID- 27492257
TI - Characterization of the tRNA ligases of pathogenic fungi Aspergillus fumigatus
and Coccidioides immitis.
AB - Yeast tRNA ligase (Trl1) is an essential trifunctional enzyme that repairs RNA
breaks with 2',3'-cyclic-PO4 and 5'-OH ends. Trl1 is composed of C-terminal
cyclic phosphodiesterase and central polynucleotide kinase domains that heal the
broken ends to generate the 3'-OH, 2'-PO4, and 5'-PO4 termini required for
sealing by an N-terminal ligase domain. Trl1 enzymes are found in all human
fungal pathogens and they are promising targets for antifungal drug discovery
because: (i) their domain structures and biochemical mechanisms are unique
compared to the mammalian RtcB-type tRNA splicing enzyme; and (ii) there are no
obvious homologs of the Trl1 ligase domain in mammalian proteomes. Here we
characterize the tRNA ligases of two human fungal pathogens: Coccidioides immitis
and Aspergillus fumigatus The biological activity of CimTrl1 and AfuTrl1 was
verified by showing that their expression complements a Saccharomyces cerevisiae
trl1Delta mutant. Purified recombinant AfuTrl1 and CimTrl1 proteins were
catalytically active in joining 2',3'-cyclic-PO4 and 5'-OH ends in vitro, either
as full-length proteins or as a mixture of separately produced healing and
sealing domains. The biochemical properties of CimTrl1 and AfuTrl1 are similar to
those of budding yeast Trl1, particularly with respect to their preferential use
of GTP as the phosphate donor for the polynucleotide kinase reaction. Our
findings provide genetic and biochemical tools to screen for inhibitors of tRNA
ligases from pathogenic fungi.
PMID- 27492259
TI - Leukocyte Adhesion Deficiency Type 1 (LAD1) with Expressed but Nonfunctional
CD11/CD18.
PMID- 27492261
TI - Absence of lung sliding is not a reliable sign of pneumothorax in patients with
high positive end-expiratory pressure.
PMID- 27492260
TI - Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a
Turkish Pediatric Oncology Center.
AB - The prevalence of lymphoma in primary immunodeficiency cases and autoimmune
diseases, as well as on a background of immunodeficiency following organ
transplants, is increasing. The lymphoma treatment success rate is known to be a
low prognosis. Our study aimed to emphasize the low survival rates in
immunodeficient vs. immunocompetent lymphoma patients and also to investigate the
effect of rituximab in patients with ataxia telangiectasia and other
immunodeficiencies. We summarized the clinical characteristics and treatment
results of 17 cases with primary immunodeficiency that developed non-Hodgkin
lymphoma (NHL) and Hodgkin lymphoma (HL) retrospectively. Seven patients were
diagnosed with ataxia-telangiectasia, two with common variable immunodeficiency,
two with selective IgA deficiency, one with X-related lymphoproliferative
syndrome, one with Wiskott-Aldrich syndrome, one with Epstein-Barr virus-related
lymphoproliferative syndrome, one with interleukin-2-inducible T-cell kinase
(ITK) deficiency, and one with lymphoma developing after autoimmune
lymphoproliferative syndrome (ALPS). One patient underwent a renal transplant. Of
the nine males and eight females (aged 3-12 years, median = 7) that developed
lymphoma, seven were diagnosed with HL and ten with NHL (seven B-cell, three T
cell). The NHL patients were started on the Berlin-Frankfurt-Munster, POG9317,
LMB-96, or R-CHOP treatment protocols with reduced chemotherapy dosages. HL cases
were started on the doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)
and/or cyclophosphamide, vincristine, procarbazine, and prednisone (COPP)
protocol, also with modified dosages. Importantly, all seven cases of HL are
alive and in remission, while six of the ten NHL patients have died. Primary
immunodeficiency is a strong predisposing factor for developing lymphoma. Low
treatment success rates relative to other lymphomas and difficulties encountered
during treatment indicate that new treatment agents are needed. While some
success has been achieved by combining rituximab with lymphoma treatment
protocols in B-NHL cases with primary immunodeficiency, the need for new
treatment approaches for these patients remains critical.
PMID- 27492262
TI - Routine biological tests in self-poisoning patients: results from an
observational prospective multicenter study.
PMID- 27492263
TI - Cyclooctyne [60]fullerene hexakis adducts: a globular scaffold for copper-free
click chemistry.
AB - The synthesis of a new highly symmetric hexakis adduct of C60 appended with 12
cyclooctyne moieties has been carried out. This compound has been used for the
copper-free strain-promoted cycloaddition reaction to a series of azides with
excellent yields. This strategy for the obtention of clicked adducts of
[60]fullerene is of special interest for biological applications.
PMID- 27492265
TI - Influence of Onabotulinumtoxin A on testes of the growing rat.
AB - Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. The
present study was planned to investigate the influence of its injection on the
maturing testicular structures in rats. Immature rats were injected in the
bilateral cremaster muscles by onabotA with three doses of (10, 20, and 40 U/kg)
three times in a 2-week interval. The effect of these injections on fertility
indices was examined. Levels of antisperm antibodies and several apoptosis
parameters were also investigated. DNA content in form of ploidy and
histopathological alterations were assessed. OnabotA-injected groups showed
decreased sperm count and semen quality, while sperm vitality, morphology, and
testosterone levels were not significantly affected. Furthermore, DNA flow
cytometric analysis confirmed delayed sperm maturation. Apoptosis markers were
significantly increased by the injections. In conclusion, onabotA injection in
growing rats adversely affected sperm count and maturation. OnabotA testicular
effects are mediated, at least partly, by apoptosis.
PMID- 27492264
TI - The immunoglobulin G1 N-glycan composition affects binding to each low affinity
Fc gamma receptor.
AB - Immunoglobulin G1 (IgG1) is the most abundant circulating human antibody and also
the scaffold for many therapeutic monoclonal antibodies (mAbs). The destruction
of IgG-coated targets by cell-mediated pathways begins with an interaction
between the IgG Fc region and multiple varieties of membrane-bound Fc gamma
receptors (FcgammaRs) on the surface of leukocytes. This interaction requires the
presence of an asparagine-linked (N-)glycan on the Fc, and variations in the N
glycan composition can affect the affinity of CD16A binding (an FcgammaR).
Contemporary efforts to glycoengineer mAbs focus on increasing CD16A affinity,
and thus treatment efficacy, but it is unclear how these changes affect affinity
for the other FcgammaRs. Here, we measure binding of the extracellular Fc-binding
domains for human CD16A and B, CD32A, B and C, and CD64 to 6 well-defined IgG1 Fc
glycoforms that cover ~85% of the pool of human IgG1 Fc glycoforms. Core alpha1-6
fucosylation showed the greatest changes with CD16B (8.5-fold decrease), CD16A
(3.9-fold decrease) and CD32B/C (1.8-fold decrease), but did not affect binding
to CD32A. Adding galactose to the non-reducing termini of the complex-type,
biantennary glycan increased affinity for all CD16s and 32s tested by 1.7-fold.
Sialylation did not change the affinity of core-fucosylated Fc, but increased the
affinity of afucosylated Fc slightly by an average of 1.16-fold for all CD16s and
CD32s tested. The effects of fucose and galactose modification are additive,
suggesting the contributions of these residues to Fc gamma receptor affinity are
independent.
PMID- 27492266
TI - Stress-dependent phosphorylation of myocardin-related transcription factor A
(MRTF-A) by the p38(MAPK)/MK2 axis.
AB - Myocardin-related transcription factor A (MRTF-A) is a known actin-regulated
transcriptional coactivator of serum response factor (SRF). Stimulation of actin
polymerization activates MRTF-A by releasing it from G-actin and thus allowing it
to bind to and activate SRF. Here, we compared protein phosphorylation in MK2/3
deficient cells rescued or not by ectopic expression of MK2 in two independent
phosphoproteomic approaches using anisomycin-treated MEF cells and LPS-stimulated
mouse macrophages, respectively. Two MRTF-A sites, Ser(351) (corresponding to
Ser(312) in human) and Ser(371) (Ser(333) in human), showed significantly
stronger phosphorylation (12-fold and 6-fold increase) in the cells expressing
MK2. MRTF-A is phosphorylated at these sites in a stress-, but not in a mitogen
induced manner, and p38(MAPK)/MK2 catalytic activities are indispensable for this
phosphorylation. MK2-mediated phosphorylation of MRTF-A at Ser(312) and Ser(333)
was further confirmed in an in vitro kinase assay and using the phospho-protein
kinase-D (PKD)-consensus motif antibody (anti-LXRXXpS/pT), the p38(MAPK)
inhibitor BIRB-796, MK2/3-deficient cells and MRTF-A phospho-site mutants.
Unexpectedly, dimerization, subcellular localization and translocation,
interaction with actin, SRF or SMAD3 and transactivating potential of MRTF-A seem
to be unaffected by manipulating the p38(MAPK)/MK2-dependent phosphorylations.
Hence, MRTF-A is stress-dependently phosphorylated by MK2 at Ser(312) and
Ser(333) with so far undetected functional and physiological consequences.
PMID- 27492267
TI - The N-myristoylome of Trypanosoma cruzi.
AB - Protein N-myristoylation is catalysed by N-myristoyltransferase (NMT), an
essential and druggable target in Trypanosoma cruzi, the causative agent of
Chagas' disease. Here we have employed whole cell labelling with azidomyristic
acid and click chemistry to identify N-myristoylated proteins in different life
cycle stages of the parasite. Only minor differences in fluorescent-labelling
were observed between the dividing forms (the insect epimastigote and mammalian
amastigote stages) and the non-dividing trypomastigote stage. Using a combination
of label-free and stable isotope labelling of cells in culture (SILAC) based
proteomic strategies in the presence and absence of the NMT inhibitor DDD85646,
we identified 56 proteins enriched in at least two out of the three experimental
approaches. Of these, 6 were likely to be false positives, with the remaining 50
commencing with amino acids MG at the N-terminus in one or more of the T. cruzi
genomes. Most of these are proteins of unknown function (32), with the remainder
(18) implicated in a diverse range of critical cellular and metabolic functions
such as intracellular transport, cell signalling and protein turnover. In
summary, we have established that 0.43-0.46% of the proteome is N-myristoylated
in T. cruzi approaching that of other eukaryotic organisms (0.5-1.7%).
PMID- 27492268
TI - The editorial policy of Intensive Care Medicine.
PMID- 27492269
TI - Ten things to know about critically ill elderly patients.
PMID- 27492270
TI - Ten tips for managing critically ill patients with sickle cell disease.
PMID- 27492271
TI - Antibiotic stewardship: do not rely on de-escalation alone.
PMID- 27492272
TI - End-of-life care in the ICU: semper ad meliora (always strive for improvement).
PMID- 27492274
TI - Direct carbon-carbon bond formation via reductive soft enolization: a syn
selective Mannich addition of alpha-iodo thioesters.
AB - The beta-amino carboxylic acid moiety is a key feature of numerous important
biologically active compounds. We describe a syn-selective direct Mannich
addition reaction that uses alpha-iodo thioesters and sulfonyl imines and
produces beta-amino thioesters. Enolate formation is achieved by reductive soft
enolization. The products of the reaction provide straightforward access to
biologically important beta-lactams through a variety of known reactions.
PMID- 27492273
TI - Proton Pump Inhibitors Are Not Associated With Acute Kidney Injury in Critical
Illness.
AB - Recent epidemiologic data linking proton pump inhibitor (PPI) use to acute and
chronic kidney dysfunction is yet to be validated in other populations, and
mechanisms have not been explored. Using a large, well phenotyped inception
cohort of 15 063 critically ill patients, we examined the risk of acute kidney
injury (AKI), as defined by the Kidney Disease Improving Global Outcomes criteria
guidelines, according to prior use of a PPI, histamine-2 receptor antagonist (H2
RA), or neither. A total of 3725 (24.7%) patients reported PPI use prior to
admission, while 905 (6.0%) patients reported H2 RA use. AKI occurred in 747
(20.0%) and 163 (18.0%) of PPI and H2 RA users respectively, compared to 1712
(16.2%) of those not taking acid suppressive medications. In unadjusted analysis,
PPI and H2 RA users had a 28% (95%CI 1.17-1.41, P < .001) and 10% (95%CI 0.91
1.30, P = .31) higher risk of AKI compared to those taking neither class of
medication. However, in sequential models that included adjustment for
demographics, cardiovascular comorbidities, indications for PPI use, and severity
of illness, the effect of PPI on the risk of AKI was attenuated, and in the
adjusted analysis, PPI was not associated with AKI (OR 1.02; 95%CI 0.91-1.13, P =
.73). The presence of sterile pyuria and hypomagnesemia did not modify the
association between PPI use and AKI. In summary, after adjustment for
demographics, illness severity, and the indication for PPI use, PPI use prior to
admission is not associated with critical illness AKI.
PMID- 27492275
TI - Emergency Medical Service Providers' Perspectives towards Management of the
Morbidly Obese.
AB - OBJECTIVE: Obesity is a growing epidemic in the United States with increasing
burden to the health care system. Management and transport of the morbidly obese
(MO) pose challenges for Emergency Medical Services (EMS) providers. Though
equipment and resources are being directed to the transport of the obese, little
research exists to guide these efforts. To address this, the author of this study
sought to assess EMS providers' perspectives on the challenges of caring for MO
patients. METHODS: An anonymous, web-based survey was distributed to all active
providers of prehospital transport of a large, urban, fire-based EMS system to
evaluate the challenges of MO patients. The definition of MO was left up to the
provider. This survey looked at various components of transport: lifting,
transport time, airway management, establishing intravenous access, drug
administration, as well as demographics, equipment, and education needs. The
survey contained yes/no, rank-order, and Likert scale questions. Data were
analyzed using descriptive statistics. The study was approved by the University
of Miami (Miami, Florida USA) Institutional Review Board. RESULTS: Of survey
participants, 71.9% felt the average weight of their patients had increased, and
100% reported to have transported a MO patient. Of calls made to EMS, 25% were
only for assistance in the house and another 25% were for non-emergent transport
to a health care facility; shortness of breath was the most common emergent
complaint. Of specific challenges to properly care for MO patients, 94.4 % ranked
lifting and/or moving the patient highest, followed by airway management,
intravenous access, and measuring vital signs. A total of 43.8% of respondents
felt that MO patients require at least six to eight EMS personnel to transport
patients while 31.8% felt more than eight providers were necessary. Greater than
81.3% felt it would be beneficial to receive more training and 90.4% felt more
equipment was needed. Of participants, 68.8 % felt that MO patients did not
receive the same standard of care. CONCLUSIONS: Surveyed participants reported
that patient's weights are increasing with all having transported a MO patient.
Despite the majority of transports being for non-emergent problems, providers
felt more training would be beneficial, that equipment available does not meet
needs, and that the MO pose challenges to appropriate patient care. Cienki JJ .
Emergency Medical Service providers' perspectives towards management of the
morbidly obese. Prehosp Disaster Med. 2016;31(5):471-474.
PMID- 27492276
TI - The Role of Psychological Factors in the Perception of Postneedling Soreness and
the Influence of Postneedling Intervention.
AB - BACKGROUND: Myofascial trigger point dry needling is frequently associated with
postneedling soreness, which can generate patient dissatisfaction and reduced
treatment adherence. Psychological factors may influence the perception of
postneedling soreness and the effectiveness of postneedling soreness treatments.
OBJECTIVES: The objectives of the present study were to determine whether
catastrophizing, kinesiophobia, pain anxiety, and fear of pain are significant
predictors of postneedling soreness over time; and to analyze whether the
relationships between psychological variables and postneedling soreness vary as a
function of the postneedling soreness intervention, which included ischemic
compression, placebo or control (without treatment). DESIGN: Repeated-measures
observational study nested within a randomized controlled trial. SETTING:
University community. PARTICIPANTS: Healthy volunteers (N = 90; 40 men and 50
women) 18 to 39 years of age (mean +/- standard deviation 22 +/- 3 years).
METHODS: Catastrophizing, kinesiophobia, pain anxiety, and fear of pain were
evaluated as possible predictors of postneedling pain before dry needling in a
latent myofascial trigger point in the upper trapezius muscle. Participants were
then divided into a treatment group that received ischemic compression as a
postneedling intervention, a placebo group that received sham ischemic
compression, and a control group that did not receive any treatment. MAIN OUTCOME
MEASUREMENTS: Pain during needling and postneedling soreness were quantified
using a visual analogue scale during needling, after treatment, and at 6, 12, 24,
and 48 hours. RESULTS: A multilevel analysis revealed that individuals who
exhibited more catastrophic thinking showed less postneedling soreness intensity
immediately after needling in all participants (beta = -0.049). Pain-related
anxiety was linked to greater immediate postneedling soreness in the compression
condition (beta = 0.057). Finally, participants who exhibited more catastrophic
thinking showed a slower rate of decline in postneedling soreness levels over
time in the compression condition (beta = 0.038). CONCLUSIONS: Catastrophizing
was associated with lower levels of postneedling soreness immediately after
needling in all subjects. Although ischemic compression seems to be a useful
procedure to reduce postneedling soreness, its efficacy could be slightly reduced
in patients presenting higher scores of pain-related anxiety. Psychological
procedures may help to correct the distorted pain expectancies associated with
needling interventions and might also improve the effectiveness of ischemic
compression. LEVEL OF EVIDENCE: II.
PMID- 27492278
TI - Umbilical cord care: national survey, literature review and recommendations.
AB - BACKGROUND: The basic principle of umbilical cord (UC) care is to keep it clean
and dry, as this provides the fastest and safest UC healing. OBJECTIVE: To
evaluate Slovenian UC care practice and compare its consistency with current
international recommendations. METHODS: A questionnaire covering UC care from
birth to complete healing of the umbilical wound was sent to all Slovenian
primary-, secondary- and tertiary-level pediatric centers. Three different
clinical conditions of the newborn's umbilicus were defined: healthy umbilicus
(HU), umbilicus at risk (UR) and unhealthy umbilicus (UU). RESULTS: The study
revealed a correlation between the clinical condition of the umbilicus, the
frequency of UC care and the antiseptic usage in both the outpatient and
inpatient UC care groups. HU was treated less frequently than UR and
significantly less than UU. In both groups, these two conditions were also
indications for UC care with antiseptic. The frequency of antiseptic usage for HU
care was significantly lower in the outpatient care group. CONCLUSIONS: Slovenian
UC care follows the general international recommendations. Based on these and our
experience, we formulated recommendations for adjustments to UC care, depending
on the clinical condition of the umbilicus, in order to prevent important
complications.
PMID- 27492277
TI - E-cigarette use among women of reproductive age: Impulsivity, cigarette smoking
status, and other risk factors.
AB - INTRODUCTION: The study aim was to examine impulsivity and other risk factors for
e-cigarette use among women of reproductive age comparing current daily cigarette
smokers to never cigarette smokers. Women of reproductive age are of special
interest because of the additional risk that tobacco and nicotine use represents
should they become pregnant. METHOD: Survey data were collected anonymously
online using Amazon Mechanical Turk in 2014. Participants were 800 women ages 24
44years from the US. Half (n=400) reported current, daily smoking and half
(n=400) reported smoking <100 cigarettes lifetime. Participants completed
questionnaires regarding sociodemographics, tobacco/nicotine use, and impulsivity
(i.e., delay discounting & Barratt Impulsiveness Scale). Predictors of smoking
and e-cigarette use were examined using logistic regression. RESULTS: Daily
cigarette smoking was associated with greater impulsivity, lower education, past
illegal drug use, and White race/ethnicity. E-cigarette use in the overall sample
was associated with being a cigarette smoker and greater education. E-cigarette
use among current smokers was associated with increased nicotine dependence and
quitting smoking; among never smokers it was associated with greater impulsivity
and illegal drug use. E-cigarette use was associated with hookah use, and for
never smokers only with use of cigars and other nicotine products. CONCLUSIONS: E
cigarette use among women of reproductive age varies by smoking status, with use
among current smokers reflecting attempts to quit smoking whereas among non
smokers use may be a marker of a more impulsive repertoire that includes greater
use of alternative tobacco products and illegal drugs.
PMID- 27492279
TI - RpoE promotes invasion and intracellular survival by regulating SPI-1 and SPI-2
in Salmonella enterica serovar Typhi.
AB - AIM: To demonstrate the role of RpoE during the later stage of hyperosmotic
stress in Salmonella. MATERIALS & METHODS: Expressions of SPI-1 and SPI-2 under
hyperosmotic stress for 120 min were investigated by a microarray, and the
invasion and intracellular survival of wild-type and DeltarpoE strains were
compared. The global differential expression of bacterial proteins between the
wild-type and DeltarpoE strains was examined after 120 min of hyperosmotic
stress. RESULTS: SPI-1 and SPI-2 were repressed, and the invasion and
intracellular survival were defected in the DeltarpoE strain. Thirteen bacterial
associated proteins and 11 secreted proteins differed significantly between the
wild-type and DeltarpoE strains. CONCLUSION: RpoE may promote invasion and
intracellular survival by regulating the expression of SPI-1 and SPI-2.
PMID- 27492281
TI - Conserved Role of bFGF and a Divergent Role of LIF for Pluripotency Maintenance
and Survival in Canine Pluripotent Stem Cells.
AB - Dogs have been widely used as a preclinical model for human disease. With the
successful generation of canine induced pluripotent stem cells (ciPSCs), the
biomedical community has a unique opportunity to study therapeutic interventions
using autologous stem cells that can benefit dogs and humans. Unlike mice and
human pluripotent cells, which are leukemia inhibitory factor (LIF)- and basic
fibroblast growth factor (bFGF)-dependent, respectively, dog iPSCs require both
growth factors simultaneously. In an effort to elucidate the role of each factor
in the control of ciPSC self-renewal, we performed a series of experiments aiming
at understanding the signaling pathways activated by them. We found that bFGF
regulates pluripotency by indirectly activating the SMAD2/3 pathway in the
presence of feeder cells, exclusively targeting NANOG expression, and inhibiting
spontaneous differentiation toward ectoderm and mesoderm. LIF activates the JAK
STAT3 pathway but does not function in the typical manner described in mouse
naive embryonic stem cells. These results show that a unique mechanism for
maintenance of pluripotency is present in ciPSC. These findings should be taken
into account when establishing stem cell differentiation protocols and may
provide more insight into pluripotency regulation in species other than mice and
humans.
PMID- 27492280
TI - Research Review: Multi-informant integration in child and adolescent
psychopathology diagnosis.
AB - BACKGROUND: An empirically based, clinically usable approach to cross-informant
integration in clinical assessment is needed. Although the importance of this
ongoing issue is becoming increasingly recognized, little in the way of solid
recommendations is currently provided to researchers and clinicians seeking to
incorporate multiple informant reports in diagnosis of child psychopathology. The
issue is timely because recent developments have created new opportunities for
improved handling of this problem. For example, advanced theories of
psychopathology and normal and abnormal child development provide theoretical
guidance for how integration of multiple informants should be handled for
specific disorders and at particular ages. In addition, more sophisticated data
analytic approaches are now available, including advanced latent variable models,
which allow for complex measurement approaches with consideration of measurement
invariance. FINDINGS: The increasing availability and mobility of computing
devices suggests that it will be increasingly feasible for clinicians to
implement more advanced methods rather than being confined to the easily
memorized algorithms of the DSM system. CONCLUSIONS: Development of models of
cross-informant integration for individual disorders based on theory and tests of
the incremental validity of more sophisticated cross-informant integration
approaches in comparison to external validation criteria (e.g. longitudinal
trajectories and outcomes, treatment response, and behavior genetic etiology)
should be a focus of future work.
PMID- 27492282
TI - Large-area, continuous and high electrical performances of bilayer to few layers
MoS2 fabricated by RF sputtering via post-deposition annealing method.
AB - We report a simple and mass-scalable approach for thin MoS2 films via RF
sputtering combined with the post-deposition annealing process. We have prepared
as-sputtered film using a MoS2 target in the sputtering system. The as-sputtered
film was subjected to post-deposition annealing to improve crystalline quality at
700 degrees C in a sulfur and argon environment. The analysis confirmed the
growth of continuous bilayer to few-layer MoS2 film. The mobility value of ~29
cm(2)/Vs and current on/off ratio on the order of ~10(4) were obtained for
bilayer MoS2. The mobility increased up to ~173-181 cm(2)/Vs, respectively, for
few-layer MoS2. The mobility of our bilayer MoS2 FETs is larger than any
previously reported values of single to bilayer MoS2 grown on SiO2/Si substrate
with a SiO2 gate oxide. Moreover, our few-layer MoS2 FETs exhibited the highest
mobility value ever reported for any MoS2 FETs with a SiO2 gate oxide. It is
presumed that the high mobility behavior of our film could be attributed to low
charged impurities of our film and dielectric screening effect by an interfacial
MoOxSiy layer. The combined preparation route of RF sputtering and post
deposition annealing process opens up the novel possibility of mass and batch
production of MoS2 film.
PMID- 27492283
TI - Two-Color, Two-Photon Imaging at Long Excitation Wavelengths Using a Diamond
Raman Laser.
AB - We demonstrate that the second-Stokes output from a diamond Raman laser, pumped
by a femtosecond Ti:Sapphire laser, can be used to efficiently excite red
emitting dyes by two-photon excitation at 1,080 nm and beyond. We image HeLa
cells expressing red fluorescent protein, as well as dyes such as Texas Red and
Mitotracker Red. We demonstrate the potential for simultaneous two-color, two
photon imaging with this laser by using the residual pump beam for excitation of
a green-emitting dye. We demonstrate this for the combination of Alexa Fluor 488
and Alexa Fluor 568. Because the Raman laser extends the wavelength range of the
Ti:Sapphire laser, resulting in a laser system tunable to 680-1,200 nm, it can be
used for two-photon excitation of a large variety and combination of dyes.
PMID- 27492284
TI - Supporting a 'bottom-up,' new, no-holds-barred, psycho-anthro-pediatrics: Making
room (scientifically) for bedsharing families.
PMID- 27492285
TI - SoyNet: a database of co-functional networks for soybean Glycine max.
AB - Soybean (Glycine max) is a legume crop with substantial economic value, providing
a source of oil and protein for humans and livestock. More than 50% of edible
oils consumed globally are derived from this crop. Soybean plants are also
important for soil fertility, as they fix atmospheric nitrogen by symbiosis with
microorganisms. The latest soybean genome annotation (version 2.0) lists 56 044
coding genes, yet their functional contributions to crop traits remain mostly
unknown. Co-functional networks have proven useful for identifying genes that are
involved in a particular pathway or phenotype with various network algorithms.
Here, we present SoyNet (available at www.inetbio.org/soynet), a database of co
functional networks for G. max and a companion web server for network-based
functional predictions. SoyNet maps 1 940 284 co-functional links between 40 812
soybean genes (72.8% of the coding genome), which were inferred from 21 distinct
types of genomics data including 734 microarrays and 290 RNA-seq samples from
soybean. SoyNet provides a new route to functional investigation of the soybean
genome, elucidating genes and pathways of agricultural importance.
PMID- 27492286
TI - Backmasking in the yeast genome: encoding overlapping information for protein
coding and RNA degradation.
AB - Backmasking is a recording technique used to hide a sound or message in a music
track in reverse, meaning that it is only audible when the record is played
backwards. Analogously, the compact yeast genome encodes for diverse sources of
information such as overlapping coding and non-coding transcripts, and protein
binding sites on the two complementary DNA strands. Examples are the consensus
binding site sequences of the RNA-binding proteins Nrd1 and Nab3 that target non
coding transcripts for degradation. Here, by examining the overlap of stable
(SUTs, stable unannotated transcripts) and unstable (CUTs, cryptic unstable
transcripts) transcripts with protein-coding genes, we show that the predicted
Nrd1 and Nab3-binding site sequences occur at differing frequencies. They are
always depleted in the sense direction of protein-coding genes, thus avoiding
degradation of the transcript. However in the antisense direction, predicted
binding sites occur at high frequencies in genes with overlapping unstable ncRNAs
(CUTs), so limiting the availability of non-functional transcripts. In contrast
they are depleted in genes with overlapping stable ncRNAs (SUTs), presumably to
avoid degrading the non-coding transcript. The protein-coding genes maintain
similar amino-acid contents, but they display distinct codon usages so that Nrd1
and Nab3-binding sites can arise at differing frequencies in antisense depending
on the overlapping transcript type. Our study demonstrates how yeast has evolved
to encode multiple layers of information-protein-coding genes in one strand and
the relative chance of degrading antisense RNA in the other strand-in the same
regions of a compact genome.
PMID- 27492287
TI - Silencing of cryptic prophages in Corynebacterium glutamicum.
AB - DNA of viral origin represents a ubiquitous element of bacterial genomes. Its
integration into host regulatory circuits is a pivotal driver of microbial
evolution but requires the stringent regulation of phage gene activity. In this
study, we describe the nucleoid-associated protein CgpS, which represents an
essential protein functioning as a xenogeneic silencer in the Gram-positive
Corynebacterium glutamicum CgpS is encoded by the cryptic prophage CGP3 of the C.
glutamicum strain ATCC 13032 and was first identified by DNA affinity
chromatography using an early phage promoter of CGP3. Genome-wide profiling of
CgpS binding using chromatin affinity purification and sequencing (ChAP-Seq)
revealed its association with AT-rich DNA elements, including the entire CGP3
prophage region (187 kbp), as well as several other elements acquired by
horizontal gene transfer. Countersilencing of CgpS resulted in a significantly
increased induction frequency of the CGP3 prophage. In contrast, a strain lacking
the CGP3 prophage was not affected and displayed stable growth. In a
bioinformatics approach, cgpS orthologs were identified primarily in
actinobacterial genomes as well as several phage and prophage genomes. Sequence
analysis of 618 orthologous proteins revealed a strong conservation of the
secondary structure, supporting an ancient function of these xenogeneic silencers
in phage-host interaction.
PMID- 27492290
TI - [Confronting the Health-Related Challenges of Climate Change: Nursing Education
for the Future].
AB - Climate change is the greatest threat to public health in the 21st century. The
increasing health impact of heat waves, the increasing magnitudes and spatial
expansions of vector and water-borne diseases epidemics, and the increasing
medical burdens of biological allergic illnesses, worsening local air pollution,
and other related issues are expected to continue to increase in severity in the
near future. All of these issues are global problems that must be faced.
Adaptation strategies and action plans related to climate change are needed and
emerging. Moreover, integrating the basic concepts, scientific evidences, and new
technology into public and professional education systems is already recognized
as a priority in the national adaptation program. Nurses stand on the frontlines
of medical care and health communication. The integration of climate change and
adaptation to climate change into nursing education and training is become
increasingly important. This article reviews both the expected health impacts of
climate change and the mitigation and adaptation strategies that have been
proposed / adopted by medical care facilities around the world. Further, we
outline the current, priority needs for action in medical care facilities in
Taiwan in order to mitigate and adapt to climate-change-related healthcare
issues. Additionally, we present an integrated strategic plan for educating
healthcare professionals, including nurse, in the future. We hope that the ideas
that are presented in this paper encourage multidisciplinary cooperation and help
bridge the gap between technology development and practical application in
Taiwan's medical care system.
PMID- 27492288
TI - Evaluating the impact of single nucleotide variants on transcription factor
binding.
AB - Diseases and phenotypes caused by disrupted transcription factor (TF) binding are
being identified, but progress is hampered by our limited capacity to predict
such functional alterations. Improving predictions may be dependent on expanding
the set of bona fide TF binding alterations. Allele-specific binding (ASB)
events, where TFs preferentially bind to one of the two alleles at heterozygous
sites, reveal the impact of sequence variations in altered TF binding. Here, we
present the largest ASB compilation to our knowledge, 10 765 ASB events retrieved
from 45 ENCODE ChIP-Seq data sets. Our analysis showed that ASB events were
frequently associated with motif alterations of the ChIP'ed TF and potential
partner TFs, allelic difference of DNase I hypersensitivity and allelic
difference of histone modifications. For TF dimers bound symmetrically to DNA,
ASB data revealed that central positions of the TF binding motifs were
disproportionately important for binding. Lastly, the impact of variation on TF
binding was predicted by a classification model incorporating all the
investigated features of ASB events. Classification models using only DNase I
hypersensitivity and sequence data exhibited predictive accuracy approaching the
models with substantially more features. Taken together, the combination of ASB
data and the classification model represents an important step toward elucidating
regulatory variants across the human genome.
PMID- 27492291
TI - [Implementing and Promoting Advance Care Planning for Community Older Adults].
AB - Advance care planning (ACP) is an emerging issue in the primary care system of
Taiwan. Previous studies have attributed benefits to various types of ACP in
diverse ranges of healthcare settings and populations. However, few older adults
in Taiwan have had the opportunity to discuss ACP or to complete their advance
directives. The present article takes the perspective of community health nursing
to describe the international development and current status of ACP in the
community in Taiwan. Furthermore, the intervention models and available resources
of ACP are described. We look forward to healthcare professionals using ACP to
assist greater numbers of community older adults, thus enhancing their terminal
stage quality of life.
PMID- 27492289
TI - Replication-dependent and independent mechanisms for the chromosome-coupled
persistence of a selfish genome.
AB - The yeast 2-micron plasmid epitomizes the evolutionary optimization of selfish
extra-chromosomal genomes for stable persistence without jeopardizing their
hosts' fitness. Analyses of fluorescence-tagged single-copy reporter plasmids
and/or the plasmid partitioning proteins in native and non-native hosts reveal
chromosome-hitchhiking as the likely means for plasmid segregation. The
contribution of the partitioning system to equal segregation is bipartite-
replication-independent and replication-dependent. The former nearly eliminates
'mother bias' (preferential plasmid retention in the mother cell) according to
binomial distribution, thus limiting equal segregation of a plasmid pair to 50%.
The latter enhances equal segregation of plasmid sisters beyond this level,
elevating the plasmid close to chromosome status. Host factors involved in
plasmid partitioning can be functionally separated by their participation in the
replication-independent and/or replication-dependent steps. In the hitchhiking
model, random tethering of a pair of plasmids to chromosomes signifies the
replication-independent component of segregation; the symmetric tethering of
plasmid sisters to sister chromatids embodies the replication-dependent
component. The 2-micron circle broadly resembles the episomes of certain
mammalian viruses in its chromosome-associated propagation. This unifying feature
among otherwise widely differing selfish genomes suggests their evolutionary
convergence to the common logic of exploiting, albeit via distinct molecular
mechanisms, host chromosome segregation machineries for self-preservation.
PMID- 27492292
TI - [The Impacts of Widowhood on the Health and Life of Elderly People and R elated
Nursing Care].
AB - Widowhood, an unavoidable and stressful situation, has been associated with
negative effects in elderly people during later life. This article reviews and
summarizes the influences of widowhood on the health, daily life, and social life
of elderly people. The influences of widowhood on elderly people may vary by
gender, spousal relationship, and cohort background. In order to provide nursing
care as early as possible, nurses must cooperate with professionals from social
welfare and / or community-support systems to identify high-risk widowed elderly.
When nurses assess the influences of widowhood on elderly people, they should
consider the interactions among gender, spousal relationship, and cohort
background. Furthermore, nurses may apply various strategies based on the needs
of elderly people to improve the health and quality of life of patients.
Suggestions include providing appropriate nursing care, offering positive social
support, adjusting daily-life routines, and arranging activity programs based on
care-recipient interests and resources.
PMID- 27492293
TI - [The Use of Telemedicine Interventions to Improve Hypertension Management Among
Racial Ethnic Minorities: A Systematic Review].
AB - BACKGROUND: Racial ethnic minorities are one of the fastest growing populations
in Taiwan. In recent years, there has been an increase in literature addressing
the efficacy of home blood-pressure (BP) management that uses telemedicine
interventions in general healthcare and community settings. However, no study or
systematic literature review has yet assessed the effectiveness of using
telemedicine HTN interventions in Taiwan's indigenous, new-immigrant, and other
minority populations. PURPOSE: The purpose of the present paper is to review the
current literature on the use of telemedicine interventions to assist HTN
management among racial ethnic minorities. METHODS: A comprehensive literature
search was conducted for full-text articles that were published between January
2000 and December 2015 using the following databases: PubMed, WEB of Science,
CINAHL (Cumulative Index to Nursing & Allied Health Literature), PsycINFO,
Science Direct, ProQuest, Medline, Cochrane Library, National Dissertations and
Theses, and airiti Library. The search used the following key search terms both
alone and in combination: hypertension, blood pressure, management, telemedicine,
telehealth, ehealth, and digital health. The studies were thoroughly assessed
under the guidelines of Preferred Reporting Items for Systematic Reviews and Meta
Analyses (PRISMA). A total of 6 articles met the criteria for using keywords
related to racial ethnic minority populations and were used in the present
review. RESULTS: Findings of this systematic review show that telemedicine
interventions significantly improve HTN management. The intervention that
combined home telemonitoring with culturally competent nurse counseling calls was
identified as the best intervention for reducing BP. As the current literature on
this topic is limited to African-Americans, more research is necessary to
validate our findings. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Future studies
should target racial ethnic minorities in Taiwan in order to better understand
how to provide culturally appropriate, telemedicine-based HTN management to
Taiwan's minority populations. Further studies with a long-term follow-up plan,
randomized controlled trials, and larger sample sizes are required to support
these results.
PMID- 27492294
TI - [Nurse-Led Care Models in the Context of Community Elders With Chronic Disease
Management: A Systematic Review].
AB - BACKGROUND: Longer average life expectancies have caused the rapid growth of the
elderly as a percentage of Taiwan's population and, as a result of the number of
elders with chronic diseases and disability. Providing continuing-care services
in community settings for elderly with multiple chronic conditions has become an
urgent need. PURPOSE: To review the nurse-led care models that are currently
practiced among elders with chronic disease in the community and to further
examine the effectiveness and essential components of these models using a
systematic review method. METHODS: Twelve original articles on chronic disease
care planning for the elderly or on nurse-led care management interventions that
were published between 2000 and 2015 in any of five electronic databases:
MEDLINE, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health
Literature) Plus with Full Text, Cochrane Library, and CEPS (Chinese Electronic
Periodicals Service)were selected and analyzed systematically. RESULTS: Four
types of nurse-led community care models, including primary healthcare, secondary
prevention care, cross-boundary models, and case management, were identified.
Chronic disease-care planning, case management, and disease self-management were
found to be the essential components of the services that were provided. The care
models used systematic processes to conduct assessment, planning, implementation,
coordination, and follow-up activities as well as to deliver services and to
evaluate disease status. The results revealed that providing continuing-care
services through the nurse-led community chronic disease-care model and cross
boundary model enhanced the ability of the elderly to self-manage their chronic
diseases, improved healthcare referrals, provided holistic care, and maximized
resource utilization efficacy. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The
present study cross-referenced all reviewed articles in terms of target clients,
content, intervention, measurements, and outcome indicators. Study results may be
referenced in future implementations of nurse-led community care models as well
as in future research.
PMID- 27492295
TI - [A Survey and Analysis of Exercise Among Pregnant Women Conducted Using the
Theory of Reasoned Action].
AB - BACKGROUND: Prior research has highlighted the significant relationship between
gestational weight gain and pregnancy outcomes. Exercise is one of the main
factors that affects body weight. Therefore, exercising appropriately during
pregnancy is an important activity for promoting healthy pregnancy outcomes.
PURPOSE: To explore the status and features of maternal exercise during pregnancy
and to analyze the related influence factors using the "theory of reasoned
action" in order to provide evidence-based guidance on exercise during pregnancy.
METHODS: Convenience sampling was used to recruit pregnant women from four
hospitals of different administrative levels in Chengdu, China. A self-developed
questionnaire was used to collect data. Data were input using Epidata and
analyzed using SPSS 21.0. RESULTS: Data provided by 587 pregnant women in their
first trimester, 522 in their second trimester, and 522 in their third trimester
were used in analysis. Significant differences were found between the three
groups in terms of housework loading and lifting. Further, participants in the
third trimester were significantly more likely to exercise less than 3 times per
week and less than 30 minutes per session than their first and second trimester
peers (p < .001). Structural equation modeling identified that: behavior
intention had a significant effect on level of physical activity; attitudes and
norms affected behavior by affecting intention; monthly income and educational
background affected behavior by influencing attitude; and educational background
affected behavior by influencing perceived norms. CONCLUSIONS: The findings of
the present study support that personal situation, the family, and social norms
impact the behavior of women significantly more during pregnancy than before
pregnancy.
PMID- 27492296
TI - [Exploring the Experience of Dysmenorrhea and Life Adjustments of Women
Undergoing Traditional Chinese Medicine Treatment].
AB - BACKGROUND: Previous studies of women with dysmenorrhea have focused on menstrual
attitudes, the characteristics of menstrual pain, and self-care behavior.
Traditional Chinese Medicine (TCM) studies on dysmenorrhea, on the other hand,
have focused on the efficacy and safety of TCM treatments. Few studies have
investigated how women perceive their own TCM-treatment experience of
dysmenorrhea. PURPOSE: The objective of this study was to explore the experience
of dysmenorrhea and life adjustments of women undergoing TCM treatment. METHODS:
A semi-structured interviewing guide was used to collect data. A total of 40
dysmenorrheal women participated in the study. Individual, in-depth interviews
were conducted for about 60-90 minutes with each participant. Their speech tone,
facial expressions, and gestures during the interview process were also observed
and recorded. The findings were analyzed using content analysis via ATLAS. ti 5.2
software. RESULTS: The process that the participants used to adjust to
dysmenorrhea were distinguished into four progressive stages: "tip of the
iceberg", "ice-breaking", "tug-of-war", and "blending-in". Initially, the
participants perceived the symptoms of dysmenorrhea as the "tip of the iceberg".
They attempted to hide / ignore the initial pain until the problem gradually
worsened to the point that the symptoms began to significantly affect various
aspects of life. It was only then that the participants began to pay attention to
the problem and to seek help from TCM practitioners, which we defined as the "ice
breaking" stage. If they encountered unexpected situations with regard to the
treatment regimen, the participants entered the "tug-of-war" stage, during which
they struggled over whether to continue with TCM treatments. Afterward, the
participants gradually achieved a "blending-in" of new ideas, which allowed them
to identify the strategies that best facilitated adjustment and rebalancing.
Eventually, the participants achieved a new life balance. CONCLUSIONS: The
outcomes of the present study may be referenced for nurse-patient communications
that relate to dysmenorrhea and TCM treatment.
PMID- 27492297
TI - [The Effect of Structured Group Reminiscence Therapy on the Life Satisfaction of
Institutionalized Elderly].
AB - BACKGROUND: Long-term care institutions have become an option for older people
who are dependent in daily living. However, insufficient attention has been
focused on assessing the life satisfaction of those currently residing in these
institutions in Taiwan. Previous research indicates that group reminiscence may
improve the life satisfaction of older adults. However, there is currently no
consensus regarding the implementation and evaluation of reminiscence
interventions. PURPOSE: To examine the effect of a structured group reminiscence
protocol on the life satisfaction of institutionalized older adults. METHODS: The
study used a quasi-experimental design. A total of 48 older adults were
conveniently recruited from two long-term care institutions in southern Taiwan.
The experimental group (n = 23) received 8 weeks of structured-group reminiscence
for 40 minutes weekly, while the control group (n = 25) received routine care
from the institution. Both groups were evaluated using a life-satisfaction
questionnaire before and after the intervention and again four weeks later.
RESULTS: Life satisfaction scores were statistically similar on the pre-test and
significantly different on both post-test questionnaires for the two groups. The
scores for the experimental and control groups were pre-test: 24.22 vs 23.36 (p =
.063); post-test I: 27.22 vs 23.32 (p < .001); and post-test II: 26.43 vs 23.00
(p < .001). The mean post-test scores for the experimental group were
significantly higher than the pre-test score (p < .001). The generalized
estimating equation test showed that the overall score of life satisfaction for
the experimental group increased by 0.85-points (p = .042) more than the control
group, which is a significant difference. CONCLUSIONS / IMPLICATIONS FOR
PRACTICE: The results support that the 8-week structured group reminiscence
protocol effectively enhances life satisfaction in older adults. The results of
this study may be referenced in the continuing education of nurses working in
long-term care institutions in the context of helping nurses organize,
facilitate, and evaluate this protocol.
PMID- 27492298
TI - [The Learning Effectiveness of Nurses Participating in a Simulated Radiation
Therapy Skin Care Workshop].
AB - BACKGROUND: The skin reaction rate is 60-95% in cancer patients that receive
radiation therapy. This therapy is likely to cause physical and mental discomfort
and prolong treatment for patients. The current emphasis on lectures rather than
practice to help nurses learn proper skin care practices likely imposes
difficulties for nurses to handle various clinical situations. PURPOSE: To
investigate the learning effectiveness of a simulated radiation therapy skin care
workshop for nurses. METHODS: A total of 34 nurses at a hospital in one health
system in northern Taiwan who had never used radiation therapy to provide care to
patients were enrolled in this quasi-experimental study. A single group pretest,
posttest and post-posttest (6 weeks after intervention) approach was used. At the
simulated radiation therapy skin care workshop, we used teaching strategies
including Ausubel's direct instruction teaching method and practice on simulated
wounds on pig skins. Outcomes were evaluated using "the questionnaire of
radiation therapy skin care" and "direct observation of procedural skills
checklist". RESULTS: The results from the simulated radiation therapy skin care
workshop were analyzed using GEE (generalized estimating equation). The post
posttest and posttest scores increased significantly; knowledge mean score 3.14
(< .001) vs 2.64 (< .001), attitude mean score 2.06 (p < .05) vs 2.24 (p < .001),
and skill mean score 2.79 (p < .001) vs 1.68 (p < .001). CONCLUSIONS: The
simulated radiation therapy skin care workshop demonstrated significant and
positive effects on learning outcomes. Therefore, we recommend incorporating this
workshop into clinical nursing education and training strategies in the future.
PMID- 27492299
TI - [Construction and Validation of a Chronic Kidney Disease Self-Care Scale].
AB - BACKGROUND: As the prevalence of chronic kidney disease (CKD) increases, it is
important to understand the self-care behavior of CKD patients. OBJECTIVES: To
construct a CKD self-care scale and evaluate its metric properties. METHODS:
Through literature review and clinical experience, question items were
constructed and validated using item analysis. Factors analysis was used to
validate the reliability and validity of the resultant questionnaire in a cross
sectional study. RESULTS: Six subscales containing a total of 20 items were
extracted from the original CKD self-care scale using item and exploratory factor
analysis. After performing three-time model goodness of fit, only five subscales
including regular medication (5 items), diet control (4 items), regular exercise
(3 items), smoking habits (2 items), and blood pressure management (2 items) were
included in the final scale. The total explained variance of the final subscales
was 74.96%. The reliability of the scale was examined and found to be
satisfactory. Each absolute factor loading value fell between .72 and .94. The
Cronbach's alpha for the overall scale was .83 and those for the five subscales
were .83, .83, .94, .81, and .87, respectively. CONCLUSIONS / IMPLICATIONS FOR
PRACTICE: Appropriate assessment tools that allow CKD health educators to
evaluate the self-care behaviors of patients effectively are needed. The valid
and reliable CKD self-care scale that was developed in the present study is able
to assist CKD health educators to quickly evaluate the self-care behavior of
patients and to make appropriate health plans.
PMID- 27492300
TI - [A Chinese Philosophical Foundation for the Sacred Mission of Nurses: The Ways of
Heaven and Life are Correlated].
AB - Clinical nursing practice uses professional nursing techniques, empathy, and
moral judgment to help relieve the pain of patients who are suffering physically
or mentally from trauma or illness. Thus, nursing involves sacred tasks.
According to Confucian reasoning, morality is expressed through everyday actions.
Providing care to patients arouses concern and sympathy in the caregiver, which
induces him or her to fully apply professional knowledge to this task. This
conduct demonstrates the moral conscience of nurses. The Chinese adage "Tian-tao
hsing-ming hsiang kuan tung" (the way of heaven and life are correlated),
attributed to Northern Song dynasty scholar Zhang Tsai, aptly explains the sacred
mission of the nursing profession. Zhang held that all humans are born with a
conscience that is given by heaven. However, human senses and desires may
suppress this conscience. As Zhang Tsai suggested, the conscience must be
cultivated in order to be manifested. The increase in recent years of
international academic discussion / research related to the value and meaning of
nursing and of exploration into how to promote the moral competence of nurses,
not only provide support to Zhang's argument that "tian-tao" and "hsing-ming" are
correlated but also provide positive momentum toward enhancing the self-worth of
nurses and enabling patients to receive better care.
PMID- 27492301
TI - [Application of the 6-Minute Walking Test and Shuttle Walking Test in the
Exercise Tests of Patients With COPD].
AB - Exercise training improves the management of stable chronic obstructive pulmonary
disease (COPD). COPD patients benefit from exercise training programs in terms of
improved VO2 peak values and decreased dyspnea, fatigue, hospital admissions, and
rates of mortality, increasing exercise capacity and health-related quality of
life (HRQOL). COPD is often associated with impairment in exercise tolerance.
About 51% of patients have a limited capacity for normal activity, which often
further degrades exercise capacity, creating a vicious circle. Exercise testing
is highly recommended to assess a patient's individualized functions and
limitations in order to determine the optimal level of training intensity prior
to initiating an exercise-training regimen. The outcomes of exercise testing
provide a powerful indicator of prognosis in COPD patients. The six-minute
walking test (6MWT) and the incremental shuttle-walking test (ISWT) are widely
used in exercise testing to measure a patient's exercise ability by walking
distances. While nursing-related articles published in Taiwan frequently cite and
use the 6MWT to assess exercise capacity in COPD patients, the ISWT is rarely
used. This paper introduces the testing method, strengths and weaknesses, and
application of the two tests in order to provide clinical guidelines for
assessing the current exercise capacity of COPD patients.
PMID- 27492302
TI - [The Impact of Sunlight Exposure on the Health of Older Adults].
AB - Appropriate exposure to sunlight not only contributes to the production of
vitamin D, which has been associated with enhanced bone health, mood, and
cognitive functions, but also regulates the secretion of melatonin, which has
been associated with the mediation of circadian rhythms, improved sleep quality,
and optimized physical and social activity in the elderly. However, damage to the
skin, eyes, and immune system has also been widely associated with long-term
exposure to sunlight. Several studies have shown that many elderly, especially
those that reside in institutions, do not receive sufficient sunlight exposure.
Institutionalized elderly tend to participate in indoor activities and spend
significant periods of time alone and asleep in front of the television.
Furthermore, factors such as poor health, environmental design, indoor/outdoor
preference, and activity design may impact the access of institutionalized
elderly to sunlight more than their non-institutionalized peers. Therefore, we
suggest that in addition to obtaining sufficient levels of vitamin D from their
diet and from supplements, the elderly should perform outdoor activities for 20
30 minutes a day for five days each week. Furthermore, we suggest that the
environment of the care facility should be made be more accessible and that some
activities should be held outdoors.
PMID- 27492303
TI - [To Push or Not to Push? Reflections on the Uterine Fundal Pressure Application
in the Second Stage of Labor].
AB - Women who undergo vaginal birth apply uterine fundal pressure during the second
stage of labor. Uterine fundal pressure is done manually with the practitioner's
forearms, elbows, or palms pressed on the uterine fundus at a 30 degrees to 45
degrees angle to the maternal spine in the direction of the pelvis. The pressure
is applied in the longitudinal direction. Gentle, firm, and steady pressure is
recommended. The various side effects of applying uterine fundal pressure
include: uterine rupture, postpartum urinary retention, severe perineal trauma
and pain, rib fracture, postpartum dyspareunia, and potential neonatal distress
or trauma. Therefore, caution is recommended in the application of uterine fundal
pressure. Thus, only well-trained and experienced medical staff or nurses should
be allowed to practice this intervention.
PMID- 27492304
TI - [Exploration of Eating Difficulties of Patients With Dementia].
AB - The number of people living with dementia is growing as the average age of the
population rises. Eating difficulties are a common problem for dementia patients
and their caregivers. The etiology of these difficulties is often complicated.
Weight loss, poor nutrition, aspiration pneumonia, and associated medical
admissions or even mortality may occur as soon as an eating difficulty develops.
This paper presents a literature review of the eating difficulties of dementia
patients. The process of eating involves four stages: recognizing food, taking
food into the mouth, chewing, and swallowing. We discuss the causes and clinical
manifestations of eating difficulties at each of these stages and introduce an
intervention for overcoming eating difficulties, aiming at providing choices of
methods to improve eating behavior. The author hopes that this review will help
medical personnel / caregivers enhance their understanding of the etiology and
the clinical manifestation of eating difficulties in dementia patients, evaluate
the overall condition of their patient(s), and provide an appropriate
intervention in order to help these patients experience the most comfortable and
non-invasive ways of eating or feeding, improve their quality of eating, and
realize with their family improved spiritual well-being.
PMID- 27492305
TI - [An Experience Promoting the Interdisciplinary Care Model for Dengue Fever].
AB - Emergency departments represent the first line in facing major healthcare events.
During major epidemic outbreaks, patients crowding into the emergency departments
increase the wait time for patients and overload the staffs that are on duty. The
dengue fever outbreak in southern Taiwan during the summer 2015 presented a huge
management challenge for physicians and nurses in local hospitals. We responded
to this challenge by integrating resources from different hospital departments.
This strategy successfully increased group cohesiveness among the medical team,
ensuring that they could not only ultimately cope with the outbreak together but
also effectively provide patient-centered care. This interdisciplinary care model
may serve as a reference for medical professionals for the management of future
epidemics and similar events.
PMID- 27492306
TI - Alveolar bone loss in relation to toll-like receptor 4 and 9 genotypes and
Porphyromonas gingivalis carriage.
AB - Toll-like receptors (TLRs) are highly developed sensors to detect microbe
associated molecular patterns. Functional polymorphisms of the genes TLR4 and
TLR9 were found to be associated with alveolar bone loss in a Porphyromonas
gingivalis-induced periodontitis model in mice. Our aim was to examine whether
such an association can be detected in a group of Finnish adults. Polymorphisms
of TLR4 Asp299Gly (rs4986790) and TLR9 rs187084 (1486 T/C) were genotyped by
pyrosequencing and PCR from the saliva samples of 223 adults (age range 40-60
years). Alveolar bone loss, measured from panoramic radiographs, were compared
between TLR genotype groups according to subjects' salivary carriage of P.
gingivalis, measured using a single copy gene-based real-time PCR. The
frequencies of TLR4 wild type and heterozygote variants were 87.4 % and 12.6 %,
respectively, while those of TLR9 wild type, heterozygote, and homozygote
variants were 25.6 %, 39.1 %, and 35.3 %, respectively. In the TLR4 heterozygote
group, P. gingivalis-positive subjects had more alveolar bone loss than P.
gingivalis-negative subjects (p = 0.027), while no difference was observed in the
wild type group. P. gingivalis-negative individuals with TLR9 heterozygotes
exhibited significantly less alveolar bone loss compared to those with TLR9 wild
type (p = 0.007). Polymorphisms of TLR4 in P. gingivalis carriers seem to expose
to alveolar bone loss. Polymorphisms of TLR9 can be protective against alveolar
bone loss in the absence of P. gingivalis.
PMID- 27492307
TI - IFITM3 and severe influenza virus infection. No evidence of genetic association.
AB - Influenza virus infection (IVI) is typically subclinical or causes a self
limiting upper respiratory disease. However, in a small subset of patients IVI
rapidly progresses to primary viral pneumonia (PVP) with respiratory failure; a
minority of patients require intensive care unit admission. Inherited and
acquired variability in host immune responses may influence susceptibility and
outcome of IVI. However, the molecular basis of such human factors remains
largely elusive. It has been proposed that homozygosity for IFITM3 rs12252-C is
associated with a population-attributable risk of 5.4 % for severe IVI in
Northern Europeans and 54.3 % for severe H1N1pdm infection in Chinese. A total of
148 patients with confirmed IVI were considered for recruitment; 118 Spanish
patients (60 of them hospitalized with PVP) and 246 healthy Spanish individuals
were finally included in the statistical analysis. PCR-RFLP was used with
confirmation by Sanger sequencing. The allele frequency for rs12252-C was found
to be 3.5 % among the general Spanish population. We found no rs12252-C
homozygous individuals in our control group. The only Spanish patient homozygous
for rs12252-C had a neurological disorder (a known risk factor for severe IVI)
and mild influenza. Our data do not suggest a role of rs12252-C in the
development of severe IVI in our population. These data may be relevant to
recognize whether patients homozygous for rs12252-C are at risk of severe
influenza, and hence require individualized measures in the case of IVI.
PMID- 27492308
TI - Freireich EJ, Miller A, Emerson CP, Ross JF. The effect of inflammation on the
utilization of erythrocyte and transferrin bound radioiron for red cell
production. Blood. 1957;12(11):972-983.
PMID- 27492309
TI - I'm TORC1-ing platelets and thromboembolism.
PMID- 27492310
TI - FBXO11: a novel germinal center B-cell regulator?
PMID- 27492311
TI - Versican vs versikine: tolerance vs attack.
PMID- 27492312
TI - ROS: novel regulators of thrombopoiesis.
PMID- 27492313
TI - [Disability studies: social exclusion a research subject].
AB - The article presents disability studies and elaborates, as their central feature,
the distinction between societal disability and impairment which can be described
on an individual and medical level. Disability studies define disability as
socially caused exclusion. Participation and inclusion, seen as sociopolitical
control and counter-terms, do, in fact, have a different content, depending on
usage and context. Using the example of the International Classification of
Functioning (ICF) and the United Nations Convention on the Rights of Persons with
Disabilities (UN CRPD), the respective understanding of disability is depicted.
Against this background, the deficits of implementation of the UN CRPD, as
criticized by the responsible UN Committee, are shown. Finally, a research agenda
for disability studies is outlined, that deals with, among other things,
implementation strategies and conflicts of interest in terms of inclusion,
furthering widely unquestioned economic conditions and especially the negative
impact of European austerity politics.
PMID- 27492314
TI - [Impairment - disability - participation for all : New federal reporting in light
of the UN Convention on the Rights of Persons with Disabilities].
AB - The new Federal Government's Report on Participation explores the contexts in
which impairments become disabilities for those individuals who experience them.
In parallel, it outlines the factors that foster inclusion and opportunities to
act for everyone in society - despite existing impairments.From a sociopolitical
and health policy perspective, disability refers to unequal opportunities based
on impairment. Hence, the focus here is on the equalisation of these
participation opportunities to match those of the entire population - but always
from differentiated perspectives on the various social arenas. The human rights
approach stresses protection against discrimination as well as dignity and self
determination for all. From a human resources angle, the emphasis is on the
performance of individuals in favourable conditions and the attainment of
personal goals within their actual everyday circumstances.The new reporting
concept is indebted to these perspectives and thus focuses on individual life
circumstances, while referring to the WHO's International Classification of
Functioning, Disability and Health (ICF) - an approach now validated on a global
scale. Therefore, it does not only report on measures provided by services for
persons with disabilities but, more crucially, investigates determinants on the
personal and environmental levels, unequal opportunities and the interdependency
between context and competence for particular sections of the population. Two
groups are singled out in the process: elderly persons and individuals with
mental health impairments.The participation report is part of the National Action
Plan to implement the UN Convention on the Rights of Persons with Disabilities
(UNCRPD). An independent scientific committee conceptualises the design of the
report while accompanying and commenting upon its realisation. Currently, a
second federal report on participation is emerging from the new concept.
PMID- 27492315
TI - [Accessibility barriers in the German health care system : Supporting and
inhibiting factors when establishing medical centres for mentally and multiply
disabled persons].
AB - BACKGROUND: In addition to primary and secondary special care, a special type of
care was created in the 2015 German Health Care Strengthening Act [GKV
Versorgungsstarkungsgesetz]: medical care centres for adult people with mental
and multiple disabilities (MCAMD). This closed a gap in the German healthcare
system and part of Article 25 of the UN Convention on the Rights of Persons with
Disabilities was implemented. OBJECTIVES: Experiences from pilot projects are
useful while implementing these centres. The issue is therefore: which are the
supporting (s) and inhibiting (i) factors when establishing MCAMDs in the view of
health care providers? METHODS: Based on open guided expert interviews medical
directors and initiators of existing and planned centres were interviewed. Data
analysis was done by qualitative content analysis. RESULTS: Healthcare providers
think reducing barriers in people's minds is most important. In the course of
approval procedures, reservations from different actors and institutions were
considered (i). During financial negotiations, health insurance companies
requested a characterisation of the target group using the ICD-lists, which
doesn't comply with the needs of the users (i). Implementation was only possible
with a great effort from the initiators paired with willingness from actors of
the association of statutory health insurance physicians and the health
insurances (s). CONCLUSION: This paper describes the process used to implement
MCAMDs. Potential centre providers can be inspired by these results. Further
research on the process of implementation of these medical centres is needed,
especially taking into account all involved parties.
PMID- 27492316
TI - [Recommendation for the collection and analysis of data on participation and
disability from the perspective of the World Health Organization].
AB - BACKGROUND: The Convention on the Rights of Persons with Disabilities (UNCRPD)
demands actions to improve participation of people with disability and to remove
barriers that hinder participation in society on an equal basis with others.
Policymaking in this area requires reliable and detailed data on all aspects of
disability. Up to now, there has been no standardized tool for collecting data on
disability and participation in the general population. In November 2011, WHO, in
collaboration with the World Bank, started the development of the Model
Disability Survey (MDS). The MDS addresses WHO's conceptualization of disability
as an outcome of interactions between a person with a health condition and
contextual factors. OBJECTIVES: Presentation of the development and
implementation of the MDS and the guidelines for standardized data analysis.
METHODS: The development of the MDS was performed in three phases: (1) situation
analysis and drafting an alpha version, (2) testing and piloting the alpha
version and (3) implementation. RESULTS: The MDS is consequently designed as a
survey for the general population without using filters. It has a modular
structure and consists of two parts (household questionnaire and individual
questionnaire with eight modules). This format allows for its use as a stand
alone survey as well as its integration in other (national) surveys. The MDS has
been cognitive tested, piloted and implemented in several countries. CONCLUSIONS:
The MDS is the first general population survey that provides standardized,
detailed and nuanced information on disability and participation of the general
population to monitor the implementation of the UNCRPD.
PMID- 27492317
TI - [Participation restrictions in substance use disorders : Registration by
screening and assessment instruments].
AB - BACKGROUND: Substance use disorders can contribute to severe participation
restrictions. Whether these participation restrictions are covered by assessment
instruments that are frequently used in addiction treatment services is not
known. The international Classification of Functioning, Disability and Health
(ICF) provides a framework to compare the content of different assessments.
OBJECTIVES: The aim of this study was to investigate whether assessments that are
frequently used in German addiction treatment services, cover participation
restrictions according to the ICF. MATERIALS AND METHODS: In the summer of 2015,
we asked German addiction treatment services to participate in an online survey.
Addiction treatment services were approached via the mailing lists of German
associations of addiction treatment. Respondents were asked to indicate which
assessments from a list of frequently used assessment instruments they were using
in their treatment service. The most frequently used assessments were then linked
to components of the ICF. RESULTS: A total of N = 177 addiction treatment
services responded to the survey. Most of them offered long-term rehabilitation
treatment (n = 97; 61 %) or counselling services (n = 44; 28 %). Twelve
assessments were used by more than 10 % of the respondents. The analysis revealed
a total of 491 so-called meaningful concepts that could be linked to components
of the ICF. Of these, 95 (16 %) referred to the ICF component activity and
participation. CONCLUSIONS: Frequently used assessments in addiction treatment
services include contents of the ICF component activity and participation to a
substantial degree. However, this does not mean by default that these assessments
can be used to assess participation restriction in a meaningful way.
PMID- 27492318
TI - Seroprevalence of Poliovirus Antibodies in the United States Population, 2009
2010.
AB - BACKGROUND: Polio is eliminated in the United States, with the last indigenous
transmission occurring in 1979. However, global eradication of polio has not yet
been completed, so importation of poliovirus into the U.S. is still possible.
Specimens from the 2009-10 National Health and Nutrition Examination Survey
(NHANES) were analyzed to evaluate population seroprevalence and assess overall
risk from a poliovirus importation. METHODS: We evaluated prevalence of serum
antibodies to all three poliovirus types using the National Health and Nutrition
Examination Survey during 2009-2010. RESULTS: The overall seroprevalence to
poliovirus was 93.9 % for type 1, 97.0 % for type 2, and 83.1 % for type 3.
Seroprevalence was higher for type 2 compared to the other types (p < 0.001) and
lower for type 3 compared to the other types (p < 0.001). There was a tendency
for higher seroprevalence in the younger age groups, but this varied by serotype.
CONCLUSIONS: Seroprevalence was high (83.1 %-97.0 %) for all three types of
poliovirus in the US population during 2009-2010. While there were observed
differences by serotype with type 2 having the highest seroprevalence and type 3
having the lowest, consistent with previous observations, no large immunity gaps
to poliovirus suggesting an imminent substantial population risk from a
poliovirus importation were observed at a population level.
PMID- 27492319
TI - Barriers to and Facilitators of Dietetics Education among Students of Diverse
Backgrounds: Results of a Survey.
PMID- 27492320
TI - Added Sugars Intake Across the Distribution of US Children and Adult Consumers:
1977-2012.
AB - BACKGROUND: Public health organizations in the United States have recently
increased focus on reducing population consumption of added sugars. OBJECTIVE:
The objective of this study is to provide in-depth information on national trends
in added sugars consumption and to examine both the mean and distribution of
added sugars intake from 1977 to 2012. DESIGN: We conducted a descriptive study
using six cross-sectional nationally representative surveys of food intake in the
United States: the 1977-1978 National Food Consumption Survey (n=29,668), the
1989-1991 Continuing Survey of Food Intake by Individuals (n=14,827), the 1994
1998 Continuing Survey of Food Intake by Individuals (n=19,027), the 2003-2004
National Health and Nutrition Examination Survey (NHANES; n=8,273), the 2009-2010
NHANES (n=9,042), and the 2011-2012 NHANES (n=16,451). STATISTICAL ANALYSIS: We
examined the key dependent variables, calories from added sugars and percentage
of total energy intake from added sugars, at the mean and by quintiles of added
sugars consumption for children (2 to 18 years) and adults (19 years and older)
across the survey years. We also examined trends in added sugars intakes from
foods and beverages. We used ordinary least squares regression to examine linear
trends between survey years and multinomial logistic regressions to examine
sociodemographic characteristics by quintile of added sugars consumption. We
adjusted estimates by race, income, sex, and education. RESULTS: The US mean
adjusted intake of added sugars remains high. In 2011-2012, children and adults
consumed 326 kcal/day and 308 kcal/day, respectively, of added sugars, or 14% and
17%, respectively, of total their energy. For both children and adults, there was
a considerable increase in calories from added sugars from 1977 to 2003, followed
by a substantial decline from 2003 to 2012. There was no decline in the
percentage of total energy intake from added sugars from 2003 to 2012. Changes
over time were consistent across each quintile of added sugars consumption. The
highest quintile of consumption was more likely to be male and in children was
more likely to be non-Hispanic white. CONCLUSIONS: Despite a decline in
consumption of added sugars since 2003 in the United States, mean adjusted added
sugars intakes continue to be above the recommended level of 10% of the total
energy intake. Changes in added sugars consumption from 1977 through 2012
occurred evenly across the distribution of added sugars intakes.
PMID- 27492321
TI - Predictors of professional placement outcome: cultural background, English
speaking and international student status.
AB - Placements provide opportunities for students to develop practice skills in
professional settings. Learning in placements may be challenging for culturally
and linguistically diverse (CALD) students, international students, or those
without sufficient English proficiency for professional practice. This study
investigated whether these factors, which are hypothesized to influence
acculturation, predict poor placement outcome. Placement outcome data were
collected for 854 students who completed 2747 placements. Placement outcome was
categorized into 'Pass' or 'At risk' categories. Multilevel binomial regression
analysis was used to determine whether being CALD, an international student,
speaking 'English as an additional language', or a 'Language other than English
at home' predicted placement outcome. In multiple multilevel analysis speaking
English as an additional language and being an international student were
significant predictors of 'at risk' placements, but other variables tested were
not. Effect sizes were small indicating untested factors also influenced
placement outcome. These results suggest that students' English as an additional
language or international student status influences success in placements. The
extent of acculturation may explain the differences in placement outcome for the
groups tested. This suggests that learning needs for placement may differ for
students undertaking more acculturative adjustments. Further research is needed
to understand this and to identify placement support strategies.
PMID- 27492322
TI - The importance of mentoring during educational supervision.
PMID- 27492323
TI - Basic science in integrated curricula : A medical student experience.
PMID- 27492324
TI - Modulation of endogenous antioxidant defense and the progression of kidney
disease in multi-heritage groups of patients with type 2 diabetes: PRospective
EValuation of Early Nephropathy and its Treatment (PREVENT).
AB - BACKGROUND: Diabetes is the western world's leading cause of end-stage renal
disease. Glucose-dependent, oxidative stress is linked to the development of
renal inflammation and sclerosis, which, in animal models of diabetes, can be
prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have
low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase
(GPx) and its co-factor vitamin E, which may be linked to their increased
propensity to developing end-stage renal disease. RESEARCH DESIGN AND METHODS: We
have designed a double-blind, randomized, placebo controlled study with selenium
and/or vitamin E versus placebo as the interventions for patients with type 2
diabetes and chronic kidney disease (CKD) stages 1-3. A 2 * 2 factorial design
will allow a balanced representation of the heritage groups exposed to each
intervention. The primary biochemical outcome is change in GPx activity, and
clinical outcome measure is the actual, rate of-and/or percentage change in
estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with
a marginal model for longitudinal data using Generalized Estimating Equations
corrected for measures of baseline serum antioxidant enzyme activities (GPx,
superoxide dismutase and catalase), micronutrient levels (vitamins E and C),
measures of inflammation (interleukin 6, c-reactive protein and monocyte
chemoattractant protein-1) and markers of oxidative damage (plasma 8
isoprostaglandin F2alpha and urinary 8-hydroxydeoxyguanosine). EXPECTED RESULTS:
The study will assess the relationship between GPx activity, oxidative stress,
inflammation and eGFR. It will test the null hypothesis that antioxidant therapy
does not influence the activity of GPx or other antioxidant enzymes and/or alter
the rate of change in eGFR in these patient groups. CONCLUSIONS: Outcome data on
the effect of antioxidants in human diabetic renal disease is limited. Previous
post hoc analyses have not shown a beneficial effect of vitamin E on renal
function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR,
but in patients with advanced diabetes-related chronic kidney disease its use was
associated with an increased incidence of cardiovascular events. We will explore
whether the nutritional antioxidants, vitamin E and selenium alone, or in
combination in patients at high risk of renal disease progression, forestalls a
reduction in eGFR. The study will describe whether endogenous antioxidant enzyme
defenses can be safely modified by this intervention and how this is associated
with changes in markers of oxidative stress. Trial registration ISRCTN 97358113.
Registered 21st September 2009.
PMID- 27492325
TI - The validity of a professional competence tool for physiotherapy students in
simulation-based clinical education: a Rasch analysis.
AB - BACKGROUND: Despite the recent widespread adoption of simulation in clinical
education in physiotherapy, there is a lack of validated tools for assessment in
this setting. The Assessment of Physiotherapy Practice (APP) is a comprehensive
tool used in clinical placement settings in Australia to measure professional
competence of physiotherapy students. The aim of the study was to evaluate the
validity of the APP for student assessment in simulation settings. METHODS: A
total of 1260 APPs were collected, 971 from students in simulation and 289 from
students in clinical placements. Rasch analysis was used to examine the construct
validity of the APP tool in three different simulation assessment formats:
longitudinal assessment over 1 week of simulation; longitudinal assessment over 2
weeks; and a short-form (25 min) assessment of a single simulation scenario.
Comparison with APPs from 5 week clinical placements in hospital and clinic-based
settings were also conducted. RESULTS: The APP demonstrated acceptable fit to the
expectations of the Rasch model for the 1 and 2 week clinical simulations,
exhibiting unidimensional properties that were able to distinguish different
levels of student performance. For the short-form simulation, nine of the 20
items recorded greater than 25 % of scores as 'not-assessed' by clinical
educators which impacted on the suitability of the APP tool in this simulation
format. CONCLUSION: The APP was a valid assessment tool when used in longitudinal
simulation formats. A revised APP may be required for assessment in short-form
simulation scenarios.
PMID- 27492326
TI - [Light and noise: Environmental factors in intensive care units].
PMID- 27492327
TI - Chemopreventive effect of Phaleria macrocarpa on colorectal cancer aberrant crypt
foci in vivo.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Natural products are important ingredients for
pharmaceutical applications specifically new entities for treating cancer and
other diseases. Phaleria macrocarpa is native of Indonesia and considered as a
prolific source of bioactive substances useful for chemoprevention. AIM OF THE
STUDY: To investigate the chemopreventive properties of Phaleria macrocarpa on
azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. METHODS: The
biological activities of the ethanol extract of P. macrocarpa fruits were
evaluated both in vitro and in vivo. First the extract was investigated for its
in vitro antioxidant activity by the total phenolic content and ferric reducing
antioxidant power assay. Then the chemopreventive effect of P. macrocarpa was
performed on AOM-induced aberrant crypt foci as colorectal carcinoma model in
rats. RESULT: the crude ethanolic extract of P. macrocarpa has high antioxidant
activity and modulated the oxidative stress as proved by the up-regulation of
glutathione-s-transferase and superoxide dismutase. Immunohistochemical staining
of the treated sections showed overexpression of PCNA and Bax, reduced crypt
sizes and numbers, indicating the characteristic feature of apoptotic cancer
cells. PCNA is a landmark of cell damage and turn-over and can be associated with
clinical cancer mutation. The most potent doses were 250mg/kg and 500mg/kg as
compared to 35mg/kg 5-fluorouracil. CONCLUSION: In this sense, the potential
modulation of the colorectal pathophysiological pathway by P. macrocarpa natural
compounds mostly flavonoids offer a great possibility for the discovery of new
leads towards the colorectal cancer.
PMID- 27492328
TI - Benzoate fraction from Gentiana rigescens Franch alleviates scopolamine-induced
impaired memory in mice model in vivo.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: G. rigescens Franch (Long Dan Cao in Chinese) is
a well-known TCM herb. It is clinically used with other drugs for the treatment
of brain diseases such as epilepsy, postherpetic neuralgia in China. AIM OF
STUDY: In our previous study, the 11 dihydroxybenzoates compounds with NGF
mimicking activity from G. rigescens Franch were found. In the present study, the
neurogenesis and neuroprotection of a mixture of benzoates ( n-GS) were
investigated in animal level. MATERIALS AND METHODS: The NGF mimicking activity
of n-GS from G. rigescens Franch was examined in PC12 cells. The neurogenesis
effects of n-GS were investigated in ICR mice with 5-bromo-2-deoxyuridine (BrdU)
and neuronal neclei (NeuN) double immunostaining. Furthermore, the
neuroprotection effects of n-GS on the memory in a scopolamine (SCO)-induced
mouse model were evaluated with animal behavior tests. RESULTS: The NGF-mimicking
function and neurogenesis of n-GS were observed in PC12 cells and in normal mice.
Subsequently, we investigated the effects of n-GS on the memory in a SCO-induced
mouse model. In Y-maze test, SCO significantly lowered the alternation. This
finding was reversed by n-GS and donepezil (DONE). SCO significantly impaired the
mice's performance in novel object recognition (NOR) and Morris water maze (MWM)
tests. The time spent to explore the novel object was longer in the n-GS- and
DONE-treated groups than in the SCO control group. In the MWM test, the escape
latency of n-GS- and DONE-treated groups was shorter than that of the SCO control
group. Mechanism study showed that SCO significantly reduced superoxide dismutase
(SOD) but increased the activities of acetylcholinesterase (AChE) and the levels
of malondialdehyde (MDA) in the hippocampus and cerebral cortex, which all can be
improved by n-GS and DONE. Additionally, the phosphorylation of type 1 insulin
like growth factor (IGF-1) receptor, extracellular signal-regulated kinase (ERK),
and cAMP responsive element-binding (CREB) protein in the hippocampus was
significantly up-regulated in the treatment group compared with that in the SCO
group. CONCLUSIONS: n-GS could alleviate impaired memory of the SCO-induced mice
model by inhibiting AChE activity and oxidative stress, and regulating the IGF
1R/ERK signaling pathway.
PMID- 27492329
TI - Preterm infant gut microbiota affects intestinal epithelial development in a
humanized microbiome gnotobiotic mouse model.
AB - Development of the infant small intestine is influenced by bacterial
colonization. To promote establishment of optimal microbial communities in
preterm infants, knowledge of the beneficial functions of the early gut
microbiota on intestinal development is needed. The purpose of this study was to
investigate the impact of early preterm infant microbiota on host gut development
using a gnotobiotic mouse model. Histological assessment of intestinal
development was performed. The differentiation of four epithelial cell lineages
(enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight
junction (TJ) formation was examined. Using weight gain as a surrogate marker for
health, we found that early microbiota from a preterm infant with normal weight
gain (MPI-H) induced increased villus height and crypt depth, increased cell
proliferation, increased numbers of goblet cells and Paneth cells, and enhanced
TJs compared with the changes induced by early microbiota from a poor weight gain
preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further
revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth
cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher
expression of the goblet cell and mature enterocyte marker Muc3 in villus
populations. In contrast, MPI-L microbiota failed to induce the aforementioned
changes and presented intestinal characteristics comparable to a germ-free host.
Our data demonstrate that microbial communities have differential effects on
intestinal development. Future studies to identify pioneer settlers in neonatal
microbial communities necessary to induce maturation may provide new insights for
preterm infant microbial ecosystem therapeutics.
PMID- 27492330
TI - A long noncoding RNA signature for ulcerative colitis identifies IFNG-AS1 as an
enhancer of inflammation.
AB - High-throughput technologies revealed new categories of genes, including the long
noncoding RNAs (lncRNAs), involved in the pathogenesis of human disease; however,
the role of lncRNAs in the ulcerative colitis (UC) has not been evaluated. Gene
expression profiling was used to develop lncRNA signatures in UC samples. Jurkat
T cells were activated by PMA/ionomycin subsequently interferon-gamma (IFNG) and
tumor necrosis factor (TNF)-alpha protein levels were assessed by ELISA. Anti
sense molecules were designed to block IFNG-AS1 expression. A unique set of
lncRNAs was differentially expressed between UC and control samples. Of these,
IFNG-AS1 was among the highest statistically significant lncRNAs (fold change:
5.27, P value: 7.07E-06). Bioinformatic analysis showed that IFNG-AS1 was
associated with the IBD susceptibility loci SNP rs7134599 and its genomic
location is adjacent to the inflammatory cytokine IFNG. In mouse models of
colitis, active colitis samples had increased colonic expression of this lncRNA.
Utilizing the Jurkat T cell model, we found IFNG-AS1 to positively regulate IFNG
expression. Novel lncRNA signatures differentiate UC patients with active
disease, patients in remission, and control subjects. A subset of these lncRNAs
was found to be associated with the clinically validated IBD susceptibility loci.
IFNG-AS1 was one of these differentially expressed lncRNAs in UC patients and
found to regulate the key inflammatory cytokine, IFNG, in CD4 T cells. Taking
these findings together, our study revealed novel lncRNA signatures deregulated
in UC and identified IFNG-AS1 as a novel regulator of IFNG inflammatory
responses, suggesting the potential importance of noncoding RNA mechanisms on
regulation of inflammatory bowel disease-related inflammatory responses.
PMID- 27492332
TI - Long noncoding RNAs: novel links to inflammatory bowel disease?
PMID- 27492331
TI - Role of the sodium-dependent multivitamin transporter (SMVT) in the maintenance
of intestinal mucosal integrity.
AB - Utilizing a conditional (intestinal-specific) knockout (cKO) mouse model, we have
recently shown that the sodium-dependent multivitamin transporter (SMVT) (SLC5A6)
is the only biotin uptake system that operates in the gut and that its deletion
leads to biotin deficiency. Unexpectedly, we also observed that all SMVT-cKO mice
develop chronic active inflammation, especially in the cecum. Our aim here was to
examine the role of SMVT in the maintenance of intestinal mucosal integrity
[permeability and expression of tight junction (TJ) proteins]. Our results showed
that knocking out the mouse intestinal SMVT is associated with a significant
increase in gut permeability and with changes in the level of expression of TJ
proteins. To determine whether these changes are related to the state of biotin
deficiency that develops in SMVT-cKO mice, we induced (by dietary means) biotin
deficiency in wild-type mice and examined its effect on the above-mentioned
parameters. The results showed that dietary-induced biotin deficiency leads to a
similar development of chronic active inflammation in the cecum with an increase
in the level of expression of proinflammatory cytokines, as well as an increase
in intestinal permeability and changes in the level of expression of TJ proteins.
We also examined the effect of chronic biotin deficiency on permeability and
expression of TJ proteins in confluent intestinal epithelial Caco-2 monolayers
but observed no changes in these parameters. These results show that the
intestinal SMVT plays an important role in the maintenance of normal mucosal
integrity, most likely via its role in providing biotin to different cells of the
gut mucosa.
PMID- 27492335
TI - Transcultural Adaptation and Validation of the German Version of the Vocal Tract
Discomfort Scale.
AB - OBJECTIVES: Currently, there is no standardized German questionnaire to assess
vocal tract discomfort in voice patients. The aim of this study was to evaluate
the internal consistency, reliability, and validity of the German version of the
Vocal Tract Discomfort (VTD) Scale. STUDY DESIGN: This is a cross-sectional
study. METHODS: First, a cross-cultural translation and adaptation from English
to German was performed. One hundred seven patients between the ages of 18 and 76
with voice disorders were divided into two different diagnosis-related groups
(organic and functional voice disorder) and 50 vocally healthy adults were
included. All participants completed the VTD Scale and the Voice Handicap Index
(VHI). The internal consistency of the VTD Scale was analyzed through Cronbach's
alpha coefficient. Pearson correlation between the VDT Scale and VHI total scores
was used to determine criterion validity. The VDT Scale score differences related
to diagnosis groups were assessed with analysis of variance. RESULTS: Excellent
internal consistency was found (alpha = 0.919, P < 0.05), and criterion validity
was confirmed by a high correlation between the total VTD Scale and VHI (r =
0.674). There was a significant difference between the diagnosis groups' total
VTD Scale score (F[4.135] = 15.114, P = 0.000). Furthermore, the vocally healthy
adults had significantly lower values than the two diagnosis groups (x-: 11.48, s
= 8.340). CONCLUSIONS: The German version of the VTD Scale has an excellent
internal consistency and reliability, and shows high clinical validity. Thus, it
is a useful instrument in voice diagnostics.
PMID- 27492334
TI - Pediatric intraventricular arachnoid cysts in the body of lateral ventricle:
surgical outcome and its embryologic background.
AB - PURPOSE: The aim of this study is for the surgical treatment and outcome of the
endoscopic fenestration of the arachnoid cyst located in the ventricular body to
trigone in the pediatric population. Special concern was paid for the
developmental origin of the intraventricular cysts estimated from the
postoperative follow-up neuroimagings. PATIENTS AND METHODS: Between July 2002
and June 2015, we performed endoscopic and partly CT/MRI navigated fenestrations
of intraventricular arachnoid cysts located at the body to trigone of the lateral
ventricle in ten pediatric patients aged 2 months to 5 years. Based on the long
axis of the cyst, we have opted for two surgical approaches: anterior approach
via burr hole at Kocher's point and posterior approach via burr hole at the
posterior occipital region. Fenestration was performed based on the
intraoperative findings, either ventriculocystostomy,
ventriculocystoventriculostomy, or ventriculocystocisternostomy. RESULTS:
Intraventricular arachnoid cysts located in the body-trigone region showed a
favorable outcome after endoscopic fenestration. All of the cysts shrank
postoperatively. Follow-up neuroimagings taken between 6 and 126 months after
surgery strongly suggested its relationship with the midline cisterns. Of our ten
cases, eight were suggestive for originating from the velum interpositum cistern
while two seemed to root from the quadrigeminal cistern. CONCLUSION: In the
present study, we found that endoscopic fenestration of intraventricular
arachnoid cysts in the body to trigone is a safe procedure with a satisfactory
outcome. In our limited experience, there are two anatomic backgrounds; velum
interpositum cistern and quadrigeminal cistern. Differentiation can be possible
by neuroimagings, especially those obtained after surgery.
PMID- 27492333
TI - The serine protease-mediated increase in intestinal epithelial barrier function
is dependent on occludin and requires an intact tight junction.
AB - Barrier dysfunction is a characteristic of the inflammatory bowel diseases (IBD),
Crohn's disease and ulcerative colitis. Understanding how the tight junction is
modified to maintain barrier function may provide avenues for treatment of IBD.
We have previously shown that the apical addition of serine proteases to
intestinal epithelial cell lines causes a rapid and sustained increase in
transepithelial electrical resistance (TER), but the mechanisms are unknown. We
hypothesized that serine proteases increase barrier function through trafficking
and insertion of tight junction proteins into the membrane, and this could
enhance recovery of a disrupted monolayer after calcium switch or cytokine
treatment. In the canine epithelial cell line, SCBN, we showed that matriptase,
an endogenous serine protease, could potently increase TER. Using detergent
solubility-based cell fractionation, we found that neither trypsin nor matriptase
treatment changed levels of tight junction proteins at the membrane. In a fast
calcium switch assay, serine proteases did not enhance the rate of recovery of
the junction. In addition, serine proteases could not reverse barrier disruption
induced by IFNgamma and TNFalpha. We knocked down occludin in our cells using
siRNA and found this prevented the serine protease-induced increase in TER. Using
fluorescence recovery after photobleaching (FRAP), we found serine proteases
induce a greater mobile fraction of occludin in the membrane. These data suggest
that a functional tight junction is needed for serine proteases to have an effect
on TER, and that occludin is a crucial tight junction protein in this mechanism.
PMID- 27492336
TI - Optimal Duration for Voice Rest After Vocal Fold Surgery: Randomized Controlled
Clinical Study.
AB - OBJECTIVES: Voice rest is commonly recommended after phonomicrosurgery to prevent
worsening of vocal fold injuries. However, the most effective duration of voice
rest is unknown. Recently, early vocal stimulation was recommended as a means to
improve wound healing. The purpose of this study is to examine the optimal
duration of voice rest after phonomicrosurgery. STUDY DESIGN: Randomized
controlled clinical study. METHODS: Patients undergoing phonomicrosurgery for
leukoplakia, carcinoma in situ, vocal fold polyp, Reinke's edema, and cyst were
chosen. Participants were randomly assigned to voice rest for 3 or 7
postoperative days. Voice therapy was administered to both groups after voice
rest. Grade, roughness, breathiness, asthenia, and strain (GRBAS) scale,
stroboscopic examination, aerodynamic assessment, acoustic analysis, and Voice
Handicap Index-10 (VHI-10) were performed pre- and postoperatively at 1, 3, and 6
months. Stroboscopic examination evaluated normalized mucosal wave amplitude
(NMWA). Parameters were compared between both groups. RESULTS: Thirty-one
patients were analyzed (3-day group, n = 16; 7-day group, n = 15). Jitter,
shimmer, and VHI-10 were significantly better in the 3-day group at 1 month post
operation. GRBAS was significantly better in the 3-day group at 1 and 3 months
post operation, and NMWA was significantly better in the 3-day group at 1, 3, and
6 months post operation compared to the 7-day group. CONCLUSIONS: The data
suggest that 3 days of voice rest followed by voice therapy may lead to better
wound healing of the vocal fold compared to 7 days of voice rest. Appropriate
mechanical stimulation during early stages of vocal fold wound healing may lead
to favorable functional recovery.
PMID- 27492337
TI - Transcatheter Aortic Valve Replacement Using the Portico System: 10 Things to
Remember.
AB - The Portico system (St. Jude Medical, Minneapolis, MN, USA) consists of a self
expanding valve prosthesis and a delivery system designed for transcatheter
aortic valve replacement (TAVR). We describe this system, its 10-steps
implantation procedure, and provide tips and tricks based on our personal
experience with this system.
PMID- 27492338
TI - Implementing oxygen control in chip-based cell and tissue culture systems.
AB - Oxygen is essential in the energy metabolism of cells, as well as being an
important regulatory parameter influencing cell differentiation and function.
Interest in precise oxygen control for in vitro cultures of tissues and cells
continues to grow, especially with the emergence of the organ-on-a-chip and the
desire to emulate in vivo conditions. This was recently discussed in this journal
in a Critical Review by Brennan et al. (Lab Chip (2014). DOI: ). Microfluidics
can be used to introduce flow to facilitate nutrient supply to and waste removal
from in vitro culture systems. Well-defined oxygen gradients can also be
established. However, cells can quickly alter the oxygen balance in their
vicinity. In this Tutorial Review, we expand on the Brennan paper to focus on the
implementation of oxygen analysis in these systems to achieve continuous
monitoring. Both electrochemical and optical approaches for the integration of
oxygen monitoring in microfluidic tissue and cell culture systems will be
discussed. Differences in oxygen requirements from one organ to the next are a
challenging problem, as oxygen delivery is limited by its uptake into medium.
Hence, we discuss the factors determining oxygen concentrations in solutions and
consider the possible use of artificial oxygen carriers to increase dissolved
oxygen concentrations. The selection of device material for applications
requiring precise oxygen control is discussed in detail, focusing on oxygen
permeability. Lastly, a variety of devices is presented, showing the diversity of
approaches that can be employed to control and monitor oxygen concentrations in
in vitro experiments.
PMID- 27492339
TI - Development and preliminary psychometric properties of the General Practitioner
Attitudes and Confidence Scale (GPACS-D) for dementia.
AB - BACKGROUND: International evidence suggests that dementia is under-diagnosed in
the community and that General Practitioners (GPs) are often reluctant to engage
to their fullest capability with patients who exhibit cognitive symptoms. This is
potentially reflected by a lack of GP knowledge about the syndrome. However, it
is also recognised that attitudes and confidence are important in relation to how
and to what extent a GP approaches a person with dementia. This research sought
to develop a reliable and valid measure of GPs attitudes and confidence towards
dementia. METHODS: The General Practitioner Attitudes and Confidence Scale for
Dementia (GPACS-D) was developed via a four stage process, including initial
content development, pretesting, pilot testing and psychometric evaluation,
including Principal Component Analysis (PCA). Participants were recruited for pre
testing (n = 12), test-retest (n = 55), and dementia workshop pre-and post
education evaluation (n = 215). RESULTS: The process of scale development and
psychometric evaluation resulted in a 20-item measure of GP attitudes and
confidence towards dementia, with 4 items removed due to poor reliability, low
sensitivity, or lack of model fit. Among 55 respondents who completed the scale
on two occasions with no intervening education, Kappa coefficient scores per item
ranged from fair (n = 2, candidates for removal), moderate (n = 5), substantial
(n = 15), and almost perfect (n = 2). A test of the sensitivity of item scores to
change following dementia education among 215 GPs indicated that, with the
exception of one item, all scale responses exhibited significant differences
between pre-and post-workshop scores, indicating acceptable sensitivity. With one
further item removed due to a low communality score, the final PCA undertaken
with the remaining 20 items supports a four-component solution, which accounted
for 51.9 % of the total variance. CONCLUSION: The GPACS-D provides a reliable and
preliminarily valid measure of GP attitudes and confidence towards dementia. The
scales provide useful information for medical educators and researchers who are
interested in evaluating and intervening in GP perceptions of the syndrome and
their capacity to provide effective care.
PMID- 27492340
TI - Characteristic calcaneal ossification: an additional early radiographic finding
in infants with fibrodysplasia ossificans progressiva.
AB - BACKGROUND: We have clinically encountered children with fibrodysplasia
ossificans progressiva who had abnormal calcaneal ossification. OBJECTIVE: To
evaluate whether calcaneal ossification variants are significant radiographic
findings in children with fibrodysplasia ossificans progressiva. MATERIALS AND
METHODS: Lateral feet radiographs in nine children who fulfilled the diagnostic
criteria of fibrodysplasia ossificans progressiva were reviewed. The studies were
obtained during infancy or early childhood. RESULTS: Fourteen lateral foot
radiographs of fibrodysplasia ossificans progressiva were available for this
study (ages at examination: 1-104 months). Four children ages 2 months to 11
months showed double calcaneal ossification centers; 7 children had plantar
calcaneal spurs that decreased in size with age. Overall, eight of nine children
with fibrodysplasia ossificans progressiva demonstrated double calcaneal
ossifications and/or plantar calcaneal spurs in infancy or childhood. CONCLUSION:
Double calcaneal ossification centers in early infancy and plantar calcaneal
spurs in childhood are frequently seen in children with fibrodysplasia ossificans
progressiva and may be a useful radiologic indicator for early diagnosis.
PMID- 27492342
TI - Identifying Important Attributes for Prognostic Prediction in Traumatic Brain
Injury Patients. A Hybrid Method of Decision Tree and Neural Network.
AB - BACKGROUND: Generally, traumatic brain injury (TBI) patients do not have a stable
condition, particularly after the first week of TBI. Hence, indicating the
attributes in prognosis through a prediction model is of utmost importance since
it helps caregivers with treatment-decision options, or prepares the relatives
for the most-likely outcome. OBJECTIVES: This study attempted to determine and
order the attributes in prognostic prediction in TBI patients, based on early
clinical findings. A hybrid method was employed, which combines a decision tree
(DT) and an artificial neural network (ANN) in order to improve the modeling
process. METHODS: The DT approach was applied as the initial analysis of the
network architecture to increase accuracy in prediction. Afterwards, the ANN
structure was mapped from the initial DT based on a part of the data.
Subsequently, the designed network was trained and validated by the remaining
data. 5-fold cross-validation method was applied to train the network. The area
under the receiver operating characteristic (ROC) curve, sensitivity,
specificity, and accuracy rate were utilized as performance measures. The
important attributes were then determined from the trained network using two
methods: change of mean squared error (MSE), and sensitivity analysis (SA).
RESULTS: The hybrid method offered better results compared to the DT method. The
accuracy rate of 86.3 % vs. 82.2 %, sensitivity value of 55.1 % vs. 47.6 %,
specificity value of 93.6 % vs. 91.1 %, and the area under the ROC curve of 0.705
vs. 0.695 were achieved for the hybrid method and DT, respectively. However, the
attributes' order by DT method was more consistent with the clinical literature.
CONCLUSIONS: The combination of different modeling methods can enhance their
performance. However, it may create some complexities in computations and
interpretations. The outcome of the present study could deliver some useful hints
in prognostic prediction on the basis of early clinical findings for TBI
patients.
PMID- 27492341
TI - Effect of hydration status on atrial and ventricular volumes and function in
healthy adult volunteers.
AB - BACKGROUND: Assessment of cardiac chamber volumes is a fundamental part of
cardiac magnetic resonance (CMR) imaging. While the effects of inter- and
intraobserver variability have been studied and have a recognized effect on the
comparability of serial cardiac MR imaging studies, the effect of differences in
hydration status has not been evaluated. OBJECTIVE: To evaluate the effects of
volume administration on cardiac chamber volumes. MATERIALS AND METHODS: Thirteen
healthy adults underwent a baseline cardiac MR to evaluate cardiac chamber
volumes after an overnight fast. They were then given two saline boluses of 10
ml/kg of body weight and the cardiac MR was repeated immediately after each
bolus. RESULTS: From the baseline scan to the final scan there was a significant
increase in all four cardiac chamber end-diastolic volumes. Right atrial volumes
increased 8.0%, from 61.1 to 66.0 ml/m2 (P<0.001), and left atrial volumes
increased 10.0%, from 50.0 to 55.0 ml/m2 (P<0.001). Right ventricular volumes
increased 6.0%, from 91.1 to 96.5 ml/m2 (P<0.001), and left ventricular volumes
increased 3.2%, from 87.0 to 89.8 ml/m2 (P<0.001). CONCLUSION: Hydration status
has a significant effect on the end-diastolic volumes of all cardiac chambers
assessed by cardiac MR. Thus, hydration represents a "variable" that should be
taken into account when assessing cardiac chamber volumes, especially when
performing serial imaging studies in a patient.
PMID- 27492343
TI - The Proposed ICD-11 Gender Incongruence of Childhood Diagnosis: A World
Professional Association for Transgender Health Membership Survey.
AB - ICD-11 (the eleventh edition of the World Health Organization International
Statistical Classification of Diseases and Related Health Problems) is due for
approval in 2018. For transgender health care, the most important proposals for
ICD-11 are as follows: (1) the five ICD-10 diagnoses (most notably Transsexualism
and Gender Identity Disorder of Childhood) currently in Chapter 5 (Mental and
Behavioural Disorders) will be replaced by two Gender Incongruence diagnoses, one
of Adolescence and Adulthood and the other of Childhood (GIC), and (2) these two
diagnoses will be located in a new chapter provisionally named Conditions Related
to Sexual Health. Debate on the GIC proposal has focused on whether there should
be a diagnosis for young children exploring their identity and has drawn on a
number of arguments for and against the proposal. The World Professional
Association for Transgender Health conducted a survey to examine members' views
concerning the GIC proposal, as well as an alternative framework employing non
pathologizing Z Codes. The survey was completed by 241 (32.6 %) out of 740
members. Findings indicated an even split among members regarding the GIC
proposal (51.0 % [n = 123] opposing and 47.7 % [n = 115] supporting the
proposal). However, non-US members were overall opposed to the proposal (63.9 %
[n = 46] opposing, 36.1 % [n = 26] supporting). Across the sample as a whole, and
among those expressing a view about Z Codes, there was substantial support for
their use in healthcare provision for children with gender issues (35.7 % [n =
86] of the sample supporting vs. 8.3 % [n = 20] rejecting).
PMID- 27492344
TI - Colorectal cancer in Malaysia: Its burden and implications for a multiethnic
country.
AB - BACKGROUND: This study aims to provide an analytical overview of the changing
burden of colorectal cancer and highlight the implementable control measures that
can help reduce the future burden of colorectal cancer in Malaysia. METHODS: We
performed a MEDLINE search via OVID with the Medical Subject Headings (MeSH)
terms "Colorectal Neoplasms"[Mesh] and "Malaysia"[Mesh], and PubMed with the key
words "colorectal cancer" and "Malaysia" from 1990 to 2015 for studies reporting
any clinical, societal, and economical findings associated with colorectal cancer
in Malaysia. Incidence and mortality data were retrieved from population-based
cancer registries/databases. RESULTS: In Malaysia, colorectal cancer is the
second most common cancer in males and the third most common cancer in females.
The economic burden of colorectal cancer is substantial and is likely to increase
over time in Malaysia owing to the current trend in colorectal cancer incidence.
In Malaysia, most patients with colorectal cancer have been diagnosed at a late
stage, with the 5-year relative survival by stage being lower than that in
developed Asian countries. Public awareness of the rising incidence of colorectal
cancer and the participation rates for colorectal cancer screening are low.
CONCLUSION: The efficiency of different screening approaches must be assessed,
and an organized national screening program should be developed in a phased
manner. It is essential to maintain a balanced investment in awareness programs
targeting general population and primary care providers, focused on increasing
the knowledge on symptoms and risk factors of colorectal cancer, awareness on
benefits of screening, and promotion of healthy life styles to prevent this
important disease.
PMID- 27492345
TI - Isolation, characterization, and marker utility of KCRE1, a transcriptionally
active Ty1/copia retrotransposon from Kandelia candel.
AB - Transposable elements are key players in eukaryotic genomic diversity. Due to
their high abundance, great heterogeneity, and replicative transposition, long
terminal repeat (LTR) retrotransposons are well suited as molecular markers for
breeding and biodiversity studies, whereas their utilities in non-model organisms
have been hindered by the lack of prior sequence knowledge. In this study, a
putative complete (5362 bp) LTR retrotransposon was isolated and characterized in
the mangrove species Kandelia candel (named KCRE1), and its transcription,
insertional polymorphisms and copy number variations were also investigated.
KCRE1 has all the features of a typical copia retroelement, and its transcription
initiation and termination sites were identified by 5' and 3' rapid amplification
of cDNA ends (RACE), respectively. KCRE1 exhibits high sequence similarity with
the tomato retroelement Rider and is constitutively expressed in the leaf, root,
flower, and hypocotyl tissues of K. candel. Based on KCRE1, sequence-specific
amplification polymorphism (SSAP) markers were developed to explore genetic
diversity across 30 individuals from three natural populations of K. candel in
China. Six primer combinations yielded a total of 204 SSAP bands with an averaged
percentage of polymorphic loci of 55.37 and 41.35 % at the species and population
levels, respectively. Each individual had a distinct SSAP phenotype, and 14-23
unique bands were observed for each population. Accordingly, KCRE1 was highly
abundant in the genome of K. candel and showed considerable copy number variation
among the three populations. In conclusion, KCRE1 is the first transcriptionally
active retrotransposon reported in K. candel, providing a useful tool for the
elucidation of untapped genetic diversity in mangrove genomes.
PMID- 27492346
TI - Nutrient production from dairy cattle manure and loading on arable land.
AB - OBJECTIVE: Along with increasing livestock products via intensive rearing, the
accumulation of livestock manure has become a serious issue due to the fact that
there is finite land for livestock manure recycling via composting. The nutrients
from livestock manure accumulate on agricultural land and the excess disembogues
into streams causing eutrophication. In order to systematically manage nutrient
loading on agricultural land, quantifying the amount of nutrients according to
their respective sources is very important. However, there is a lack of research
concerning nutrient loss from livestock manure during composting or storage on
farms. Therefore, in the present study we quantified the nutrients from dairy
cattle manure that were imparted onto agricultural land. METHODS: Through
investigation of 41 dairy farms, weight reduction and volatile solids (VS), total
nitrogen (TN), and total phosphorus (TP) changes of dairy cattle manure during
the storage and composting periods were analyzed. In order to support the direct
investigation and survey on site, the three cases of weight reduction during the
storing and composting periods were developed according to i) experiment, ii)
reference, and iii) theoretical changes in phosphorus content (DeltaP = 0).
RESULTS: The data revealed the nutrient loading coefficients (NLCs) of VS, TN,
and TP on agricultural land were 1.48, 0.60, and 0.66, respectively. These values
indicated that the loss of nitrogen and phosphorus was 40% and 34%, respectively,
and that there was an increase of VS since bedding materials were mixed with
excretion in the barn. CONCLUSION: As result of nutrient-footprint analyses, the
amounts of TN and TP particularly entered on arable land have been overestimated
if applying the nutrient amount in fresh manure. The NLCs obtained in this study
may assist in the development of a database to assess the accurate level of
manure nutrient loading on soil and facilitate systematic nutrient management.
PMID- 27492348
TI - Association of the Single Nucleotide Polymorphisms in RUNX1, DYRK1A, and KCNJ15
with Blood Related Traits in Pigs.
AB - The aim of this study was to detect positional candidate genes located within the
support interval (SI) regions based on the results of red blood cell, mean
corpuscular volume (MCV), and mean corpuscular hemoglobin quantitative trait
locus (QTL) in Sus scrofa chromosome 13, and to verify the correlation between
specific single-nucleotide polymorphisms (SNPs) located in the exonic region of
the positional candidate gene and the three genetic traits. The flanking markers
of the three QTL SI regions are SW38 and S0215. Within the QTL SI regions, 44
genes were located, and runt-related transcription factor 1, dual-specificity
tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A), and potassium inwardly
rectifying channel, subfamily J, member 15 KCNJ15-which are reported to be
related to the hematological traits and clinical features of Down syndrome-were
selected as positional candidate genes. The ten SNPs located in the exonic region
of the three genes were detected by next generation sequencing. A total of 1,232
pigs of an F2 resource population between Landrace and Korean native pigs were
genotyped. To investigate the effects of the three genes on each genotype, a
mixed-effect model which is the considering family structure model was used to
evaluate the associations between the SNPs and three genetic traits in the F2
intercross population. Among them, the MCV level was highly significant (nominal
p = 9.8*10-9) in association with the DYRK1A-SNP1 (c.2989 GC and (g.2988 A>G,
g.3977-325 T>C) combinations of fatty acid-binding protein4 were the superior
gene, and the superior genotype combinations across all economic traits were the
CC genotype at g.3977-325 T>C and the AACC, GACC, GGCC genotypes of (g.2988 A>G,
g.3977-325 T>C).
PMID- 27492350
TI - Allelic variation of melanocortin-1 receptor locus in Saudi indigenous sheep
exhibiting different color coats.
AB - OBJECTIVE: This study was designed to characterize the DNA polymorphisms of the
melanocortin-1 receptor (MC1R) gene in indigenous Saudi Arabian sheep breeds
exhibiting different color coats, along with individuals of the Sawaknee breed,
an exotic sheep imported from Sudan. METHODS: The complete coding region of MC1R
gene including parts of 3' and 5' untranslated regions was amplified and
sequenced from three the indigenous Saudi sheep; Najdi (generally black, n = 41),
Naeimi (generally white with brown faces, n = 36) and Herri (generally white, n =
18), in addition to 13 Sawaknee sheep. RESULTS: Five single nucleotide
polymorphisms (SNPs) were detected in the MC1R gene: two led to nonsynonymous
mutations (c.218 T>A, p.73 Met>Lys and c.361 G>A, p.121 Asp>Asn) and three led to
synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu, and
c.735 C>T, p.245 Ile>Ile). Based on these five SNPs, eight haplotypes
representing MC1R Ed and E+ alleles were identified among the studied sheep
breeds. The most common haplotype (H3) of the dominant Ed allele was associated
with either black or brown coat color in Najdi and Sawaknee sheep, respectively.
Two other haplotypes (H6 and H7) of Ed allele, with only the nonsynonymous
mutation A218T, were detected for the first time in Saudi indigenous sheep.
CONCLUSION: In addition to investigating the MC1R allelic variation in Saudi
indigenous sheep populations, the present study supports the assumption that the
two independent nonsynonymous Met73Lys and Asp121Asn mutations in MC1R gene are
associated with black or red coat colors in sheep breeds.
PMID- 27492351
TI - Behaviour of mesotrione in maize and soil system and its influence on soil
dehydrogenase activity.
AB - The aim of this study was to investigate the dissipation of mesotrione and effect
on dehydrogenase activity (DHA) in maize and soil system. The paper for the first
time describes behaviour of this herbicide applied at various doses (separately
or in mixture with other herbicide) in acidic and alkaline environment. The
experiments were conducted using the method randomized blocks in four repetition
cycles. Chemical application in seven variants at recommended doses of herbicide
were performed. The sample preparation was performed by a modified QuEChERS
method and the concentrations of mesotrione in maize and soil were determined by
the liquid chromatography with tandem mass spectrometry (LC-MS/MS). The limit of
detection was 0.0005mgkg(-1) and quantification 0.001mgkg(-1). The dissipation of
mesotrione were described according to first-order (FO) kinetics equation with
R(2) were between 0.8794 and 0.9934. The initial deposit of herbicide in soil and
maize was higher in an acidic environment (0.06-0.18mgkg(-1)). A positive
correlation between an alkaline pH and the rate of dissipation in soil was
observed. The results showed that the time after which 50% (DT50) of substance
has been degraded was different for both plant and soil. DT50 for soil was within
the range 3.2-6.0days and 2.9-4.4days, for the maize 3.9-4.8days and 3.4-4.5days
in an alkaline and an acidic environment, respectively. Concentration of
mesotrione at applicable MRL level of 0.05mgkg(-1) in maize was achieved at 0.5
5.9days and at proposed MRL of 0.01mgkg(-1) at 8.8-15.8days. The results indicate
that the application of mesotrione affected on DHA in the soil. One day after
application this herbicide, concentration of DHA in soil was lower than in
control plots, but after 21days was observed trend of increasing DHA.
PMID- 27492352
TI - Diagnosis and Management of Oesophageal Cancer in Bariatric Surgical Patients.
AB - BACKGROUND: Oesophageal cancer following bariatric surgery adds significant
complexity to an already challenging disease. There is limited data on the
diagnosis, presentation and management in these complex cases. METHODS: A
retrospective cohort study on prospectively collected data over 10 years was
conducted. The oesophago-gastric cancer database was searched for patients with
prior bariatric surgery. Data were retrieved on bariatric and cancer management.
RESULTS: We identified nine patients with oesophageal or gastro-oesophageal
junction adenocarcinoma after bariatric surgery. Mean age was 58.3 +/- 6.9 years,
and duration from bariatric surgery was 13.2 +/- 9.4 years. Weight loss at
diagnosis was 30.6 +/- 23.3 kg (excess weight loss 58.1 % +/- 29.6). Modes of
presentation were Barrett's surveillance (n = 3), reflux symptoms (n = 4) and
incidental (n = 2). Management was surgical resection (n = 4), endoscopic mucosal
resection (n = 2) and palliative (n = 3). Surgical resections were challenging
due to adhesions, obesity, luminal dilatation and scarring on the stomach. There
were two substantial leaks following gastroplasty. CONCLUSIONS: Oesophageal
cancer following bariatric surgery is a challenging problem, and surgical
resection carries high risk. A high index of suspicion is required and symptoms
investigated precipitously. Technical challenges of operating on obese patients
and the specific effects of previous bariatric procedures need to be understood,
particularly the limitations on reconstructive options.
PMID- 27492353
TI - Intussusception Involving the Roux-en-Y limb Following Gastric Bypass.
PMID- 27492354
TI - A Combined Nissen Plus Hill Hybrid Repair for Paraesophageal Hernia Improves
Clinical Outcomes and Reduces Long-Term Recurrences Compared with Laparoscopic
Nissen Alone.
AB - INTRODUCTION: We compared clinical and objective outcomes of combined Nissen-Hill
hybrid (HYB) to Nissen fundoplication (LNF) for repair of paraesophageal hernia
(PEH). METHODS: This study is a single-institution retrospective chart review of
prospectively collected data for consecutive patients undergoing PEH repair from
2006 to 2015 with at least 6 months of follow-up. Quality of life metrics
(QOLRAD, HRQL, and dysphagia), manometry, radiographic imaging, and pH testing
were administered pre- and postoperatively. RESULTS: With 319 repairs (HYB = 141,
LNF = 178), the groups were comparable in age and gender, but HYB had a higher
BMI (30.95 vs 29.27, p < 0.05), larger hernia (6 vs 5 cm, p < 0.05), and more
Barrett's esophagus (42 vs 29, p < 0.05). At a median follow-up of 22 months,
DeMeester scores were equivalent but PPI use was higher in the LNF group. All
three quality of life scores were better for HYB: GERD-HRQL 3.75 vs 7.49, p =
0.01; QOLRAD 6.59 vs 6.23, p = 0.04; and swallowing 40.71 vs 36.47, p = 0.01. At
a median follow-up of 60 months (HYB = 39, LNF = 31), anatomic recurrences and
reoperations were lower for HYB: 5 vs 45 % (p < 0.05), 2.6 vs 9.7 % (p = 0.2).
CONCLUSION: Combining Nissen and Hill for PEH repair appears to result in better
quality of life and fewer recurrences compared to LNF.
PMID- 27492356
TI - Complex odontomas hindering eruption of maxillary permanent teeth: a radiological
perspective.
PMID- 27492355
TI - Non-Elective Paraesophageal Hernia Repair Portends Worse Outcomes in Comparable
Patients: a Propensity-Adjusted Analysis.
AB - INTRODUCTION: Patients undergoing non-elective paraesophageal hernia repair
(PEHR) have worse perioperative outcomes. Because they are usually older and
sicker, however, these patients may be more prone to adverse events, independent
of surgical urgency. Our study aimed to determine whether non-elective PEHR is
associated with differential postoperative outcome compared to elective repair,
using propensity-score weighting. METHODS: We abstracted data for patients
undergoing PEHR (n = 924; non-elective n = 171 (19 %); 1997-2010). Using boosted
regression, we generated a propensity-weighted dataset. Odds of 30-day/in
hospital mortality and major complications after non-elective surgery were
determined. RESULTS: Patients undergoing non-elective repair were significantly
older, had more adverse prognostic factors, and significantly more major
complications (38 versus 18 %; p < 0.001) and death (8 versus 1 %; p < 0.001).
After propensity weighting, median absolute percentage bias across 28 propensity
score variables improved from 19 % (significant imbalance) to 5.6 % (well
balanced). After adjusting propensity-weighted data for age and comorbidity
score, odds of major complications were still nearly two times greater (OR 1.67,
CI 1.07-2.61) and mortality nearly three times greater (OR 2.74, CI 0.93-8.1)
than for elective repair. CONCLUSIONS: Even after balancing significant
differences in baseline characteristics, non-elective PEHR was associated with
worse outcomes than elective repair. Symptomatic patients should be referred for
elective repair by experienced surgeons.
PMID- 27492358
TI - Smoking and Cognition.
AB - Given the large availability of nicotinic acetylcholine receptors (nAChRs)
throughout the brain, and the wide range of neurotransmitter systems affected
(norepinephrine, serotonin and dopamine), nicotine influences a wide variety of
cognitive domains such as sensorial, motor, attention, executive function,
learning and memory. This article reviews current state of the art research on
the effects of nicotine upon cognition. There are different neurobiological
mechanisms involved in acute/chronic smoking and nicotine abstinence. Smoking
reinforcement could be due to the initial cognitive improvement, that is,
individuals can learn that smoking temporarily increases cognitive functioning
(improving some components of attention and memory). These acute nicotine effects
improve (i) cognitive performance above smokers' normal levels, and (ii)
cognitive disruption resulting from nicotine abstinence. Both neurobiological
effects act as reinforcers to nicotine use, greatly contributing to the
development of nicotine dependence. However, heavy smoking is associated with
cognitive impairment and cognitive decline in middle age. Future clinical
research should investigate the role of positive and negative cognitive effects
of nicotine in smoking cessation treatment. This is clearly an important
scientific issue, with insufficient current data from which to draw definitive
conclusions.
PMID- 27492357
TI - The multiple evolutionary origins of the eukaryotic N-glycosylation pathway.
AB - BACKGROUND: The N-glycosylation is an essential protein modification taking place
in the membranes of the endoplasmic reticulum (ER) in eukaryotes and the plasma
membranes in archaea. It shares mechanistic similarities based on the use of
polyisoprenol lipid carriers with other glycosylation pathways involved in the
synthesis of bacterial cell wall components (e.g. peptidoglycan and teichoic
acids). Here, a phylogenomic analysis was carried out to examine the validity of
rival hypotheses suggesting alternative archaeal or bacterial origins to the
eukaryotic N-glycosylation pathway. RESULTS: The comparison of several
polyisoprenol-based glycosylation pathways from the three domains of life shows
that most of the implicated proteins belong to a limited number of superfamilies.
The N-glycosylation pathway enzymes are ancestral to the eukaryotes, but their
origins are mixed: Alg7, Dpm and maybe also one gene of the glycosyltransferase 1
(GT1) superfamily and Stt3 have proteoarchaeal (TACK superphylum) origins;
alg2/alg11 may have resulted from the duplication of the original GT1 gene; the
lumen glycosyltransferases were probably co-opted and multiplied through several
gene duplications during eukaryogenesis; Alg13/Alg14 are more similar to their
bacterial homologues; and Alg1, Alg5 and a putative flippase have unknown
origins. CONCLUSIONS: The origin of the eukaryotic N-glycosylation pathway is not
unique and less straightforward than previously thought: some basic components
likely have proteoarchaeal origins, but the pathway was extensively developed
before the eukaryotic diversification through multiple gene duplications, protein
co-options, neofunctionalizations and even possible horizontal gene transfers
from bacteria. These results may have important implications for our
understanding of the ER evolution and eukaryogenesis. REVIEWERS: This article was
reviewed by Pr. Patrick Forterre and Dr. Sergei Mekhedov (nominated by Editorial
Board member Michael Galperin).
PMID- 27492359
TI - Substance-Related and Addictive Disorders as a Risk Factor of Suicide and
Homicide among Patients with ADHD: A Mini Review.
AB - OBJECTIVE: To discuss the role of substance-related and addictive disorders
(SRAD) that lead patients with attention-deficit hyperactivity disorder (ADHD) to
suicide and homicide. METHOD: Relevant articles were searched via PubMed using
several keywords related to this issue. Most of the articles included in this
review were published after 2000. RESULTS: Patients with ADHD often fall into
crises of catastrophic life events such as suicide or homicide. SRAD play an
important role in leading ADHD patients to such events. Because ADHD is
characterized by inattentiveness and impulsivity, any kinds of substances, legal
or illegal, can deteriorate ADHD symptoms, leading ADHD patients to such
catastrophic events. There are several pathways that connect ADHD with SRAD,
which are roughly divided into two ways: internalizing mental disorders and
externalizing mental disorders. The former includes depression and anxiety
disorders characterized by self-inhibition or withdrawal. The latter typically
includes conduct disorder or oppositional defiant disorder, as well as antisocial
personality disorder, characterized by aggressive or antisocial behaviors or
emotions towards others. These comorbid psychiatric disorders are apt to lead
ADHD patients to SRAD, and once these patients suffer from SRAD, risk of
catastrophic life events seems to increase due to the irreversibility of their
adverse mentality. Comorbid mental disorders with ADHD can act, at least
partially, as mediators from ADHD to SRAD. CONCLUSION: SRAD can be a critical
risk factor of suicide and homicide among patients with ADHD. Early interventions
for families with ADHD and psychiatric comorbidities may work as effective
preventive strategies against such events.
PMID- 27492360
TI - Intron sequences that stimulate gene expression in Arabidopsis.
AB - KEY MESSAGE: Related motifs strongly increase gene expression when added to an
intron located in coding sequences. Many introns greatly increase gene expression
through a mechanism that remains elusive. An obstacle to understanding intron
mediated enhancement (IME) has been the difficulty of locating the specific
intron sequences responsible for boosting expression because they are redundant,
dispersed, and degenerate. Previously we used the IMEter algorithm in two
independent ways to identify two motifs (CGATT and TTNGATYTG) that are candidates
for involvement in IME in Arabidopsis. Here we show that both motifs are
sufficient to increase expression. An intron that has little influence on
expression was converted into one that increased mRNA accumulation 24-fold and
reporter enzyme activity 40-fold relative to the intronless control by
introducing 11 copies of the more active TTNGATYTG motif. This degree of
stimulation is twice as large as that of the strongest of 15 natural introns
previously tested in the same reporter gene. Even though the CGATT and TTNGATYTG
motifs each increased expression, and CGATT matches the NGATY core of the longer
motif, combining the motifs to make TTCGATTTG reduced the stimulating ability of
the TTNGATYTG motif. Additional substitutions were used to test the contribution
to IME of other residues in the TTNGATYTG motif. The verification that these
motifs are active in IME will improve our ability to predict the stimulating
ability of introns, to engineer any intron to increase expression to a desired
level, and to explore the mechanism of IME by seeking factors that might interact
with these sequences.
PMID- 27492361
TI - Re A (A Child) and the United Kingdom Code of Practice for the Diagnosis and
Confirmation of Death: Should a Secular Construct of Death Override Religious
Values in a Pluralistic Society?
AB - The determination of death by neurological criteria remains controversial
scientifically, culturally, and legally, worldwide. In the United Kingdom,
although the determination of death by neurological criteria is not legally
codified, the Code of Practice of the Academy of Medical Royal Colleges is
customarily used for neurological (brainstem) death determination and treatment
withdrawal. Unlike some states in the US, however, there are no provisions under
the law requiring accommodation of and respect for residents' religious rights
and commitments when secular conceptions of death based on medical codes and
practices conflict with a traditional concept well-grounded in religious and
cultural values and practices. In this article, we analyse the medical, ethical,
and legal issues that were generated by the recent judgement of the High Court of
England and Wales in Re: A (A Child) [2015] EWHC 443 (Fam). Mechanical
ventilation was withdrawn in this case despite parental religious objection to a
determination of death based on the code of practice. We outline contemporary
evidence that has refuted the reliability of tests of brainstem function to
ascertain the two conjunctive clinical criteria for the determination of death
that are stipulated in the code of practice: irreversible loss of capacity for
consciousness and somatic integration of bodily biological functions. We argue
that: (1) the tests of brainstem function were not properly undertaken in this
case; (2) the two conjunctive clinical criteria set forth in the code of practice
cannot be reliably confirmed by these tests in any event; and (3) absent
authentication of the clinical criteria of death, the code of practice (in fact,
although implicitly rather than explicitly) wrongly invokes a secular definition
of death based on the loss of personhood. Consequently, the moral obligation of a
pluralistic society to honor and respect diverse religious convictions to the
greatest extent possible is being violated. Re A (A Child) is contrasted with the
US case of Jahi McMath in which the court accommodated parental religious
objection to the determination of neurological death codified in the Uniform
Determination of Death Act. We conclude that the legal system in the United
Kingdom should not favour a secular definition of death over a definition of
death that is respectful of religious values about the inviolability and sanctity
of life. We recommend the legal recognition of religious accommodation in death
determination to facilitate cultural sensitivity and compassionate care to
patients and families in a pluralistic society.
PMID- 27492362
TI - Opioid Prescribing: How Well Do We Know Ourselves?
PMID- 27492363
TI - Edaravone alleviates cisplatin-induced neurobehavioral deficits via modulation of
oxidative stress and inflammatory mediators in the rat hippocampus.
AB - Cisplatin is a chemotherapeutic agent used in the treatment of malignant tumors.
A major clinical limitation of cisplatin is its potential toxic effects,
including neurotoxicity. Edaravone, a potent free radical scavenger, has been
reported to have the neuroprotective effect against neurological deficits. The
aim of the present study was to determine the neuroprotective effect of edaravone
against cisplatin-induced behavioral and biochemical anomalies in male Wistar
rats. Our results showed that cisplatin (5mg/kg/week, i.p.) administration for
seven weeks caused marked cognitive deficits and motor incoordination in rats.
This was accompanied by oxido-nitrosative stress, neuroinflammation, NF-kappaB
activation and down-regulation of Nrf2/HO-1 gene expression level in the
hippocampus. Edaravone (10mg/kg/week, i.p.) treatment for seven weeks inhibited
the aforementioned neurobehavioral and neurochemical deficits. Furthermore,
edaravone was found to up-regulate the gene expression level of Nrf2/HO-1 and
prevented the cisplatin-induced NF-kappaB activation. These findings demonstrated
that oxido-nitrosative stress and inflammatory signaling mediators play a key
role in the development of cisplatin-induced neurobehavioral deficits which were
prevented by edaravone treatment.
PMID- 27492364
TI - Remifentanil preconditioning protects rat cardiomyocytes against hypoxia
reoxygenation injury via delta-opioid receptor mediated activation of PI3K/Akt
and ERK pathways.
AB - Remifentanil preconditioning has been demonstrated to reduce myocardial ischemia
reperfusion injury in rat hearts, while the mechanisms are not fully understood.
This study investigated the protective effects of remifentanil against hypoxia
reoxygenation injury in adult rat cardiomyocytes and the mechanisms involving
opioid receptors and downstream phosphatidylinositol-3-kinase/protein kinase B
(PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathways.
Adult rat cardiomyocytes were pretreated with remifentanil at different
concentrations and then subjected to 90min hypoxia followed by 120min
reoxygenation. The delta- (naltrindole), kappa- (nor-binaltorphimine), or MU
opioid receptor antagonist (CTOP), as well as ERK inhibitor (PD98059) or PI3K
inhibitor (wortmannin) was added before remifentanil preconditioning,
respectively. Remifentanil showed significant protective effects against hypoxia
reoxygenation injury by increasing cell survival (Trypan blue staining) while
reducing LDH activity and cell apoptosis (Hoechst staining). These effects were
markedly reversed by naltrindole and were partially blocked by nor
binaltorphimine. Pretreatment of either PD98059 or wortmannin also abolished the
protective effects of remifentanil. Following remifentanil preconditioning, the
phosphorylation level of Akt reached peak at 10min of reoxygenation. ERK
phosphorylation, however, was subsequently enhanced at 120min of reoxygenation.
The phosphorylation levels of Akt and ERK were both blocked by naltrindole, but
not nor-binaltorphimine or CTOP. Wortmannin inhibited the phosphorylation of both
Akt and ERK, whereas PD98059 suppressed the phosphorylation of ERK only. In
conclusion, our results suggested that remifentanil protected adult rat
cardiomyocytes from hypoxia-reoxygenation injury and its effects appears to be
dependent on the delta-opioid receptor mediated activation of PI3K/Akt and
subsequent ERK signaling pathways.
PMID- 27492365
TI - Ranolazine triggers pharmacological preconditioning and postconditioning in
anesthetized rabbits through activation of RISK pathway.
AB - We tested the hypothesis that ranolazine (Ran) is cardioprotective in a model of
ischemia /reperfusion and we elucidated the intracellular mechanism. Anesthetized
rabbits were subjected to is chemia and reperfusion and were divided into 5
groups: 1) Control, 2) Preconditioning (PreC), 3) Postconditioning (PostC), 4)
RanA and 5) RanB, respectively treated with intravenous ranolazine, either 10min
before or during index ischemia. Ranolazine was initially given over 60s and then
from the beginning and throughout the whole reperfusion period. The infarcted to
the risk ratio was calculated (%I/R). In a second series consisting of respective
to the first series groups, the animals were subjected to the same interventions
up to the 10th min of reperfusion where tissue samples were taken for
immunoblotting of Akt, eNOS, ERK1/2 and GSK3beta (RISK pathway). In a third
series, RanA+Wort, RanB+Wort and Wort groups were treated with ranolazine as RanA
and RanB groups but with the addition of the PI3 inhibitor Wortmaninn (Wort) and
%I/R calculated. Ranolazine reduced the % I/R in RanA and RanB compared to the
Control (23.1+/-1.7%, 17.6+/-2.0% vs 47.6+/-1.0%, P<0.05). %I/R reduction
achieved in the RanA and RanB groups was comparable to that observed in PreC and
PostC (16.3+/-2.1%, 26.2+/-2.1%, respectively P<0.05 vs Control). Phosphorylation
of Akt, ERK1/2, eNOS and GSK3beta were higher in PreC, PostC and in both
ranolazine treated groups. Wortmannin abrogated ranolazine's %I/R reduction
(RanA+Wort 31.4+/-1.7%, RanB+Wort 32.4+/-2.4%). Ranolazine reduces %I/R and
triggers cardioprotection with a similar to conditioning mechanism which
upregulates the RISK pathway.
PMID- 27492366
TI - CellShape: A user-friendly image analysis tool for quantitative visualization of
bacterial cell factories inside.
AB - Visualization of the intracellular constituents of individual bacteria while
performing as live biocatalysts is in principle doable through more or less
sophisticated fluorescence microscopy. Unfortunately, rigorous quantitation of
the wealth of data embodied in the resulting images requires bioinformatic tools
that are not widely extended within the community-let alone that they are often
subject to licensing that impedes software reuse. In this context we have
developed CellShape, a user-friendly platform for image analysis with subpixel
precision and double-threshold segmentation system for quantification of
fluorescent signals stemming from single-cells. CellShape is entirely coded in
Python, a free, open-source programming language with widespread community
support. For a developer, CellShape enhances extensibility (ease of software
improvements) by acting as an interface to access and use existing Python
modules; for an end-user, CellShape presents standalone executable files ready to
open without installation. We have adopted this platform to analyse with an
unprecedented detail the tridimensional distribution of the constituents of the
gene expression flow (DNA, RNA polymerase, mRNA and ribosomal proteins) in
individual cells of the industrial platform strain Pseudomonas putida KT2440.
While the CellShape first release version (v0.8) is readily operational, users
and/or developers are enabled to expand the platform further.
PMID- 27492367
TI - The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E
BPs.
AB - Adult stem cells must limit their rate of protein synthesis, but the underlying
mechanisms remain largely unexplored. Differences in protein synthesis among
hematopoietic stem cells (HSCs) and progenitor cells did not correlate with
differences in proteasome activity, total RNA content, mRNA content, or cell
division rate. However, adult HSCs had more hypophosphorylated eukaryotic
initiation factor 4E-binding protein 1 (4E-BP1) and 4E-BP2 as compared with most
other hematopoietic progenitors. Deficiency for 4E-BP1 and 4E-BP2 significantly
increased global protein synthesis in HSCs, but not in other hematopoietic
progenitors, and impaired their reconstituting activity, identifying a mechanism
that promotes HSC maintenance by attenuating protein synthesis.
PMID- 27492368
TI - Transcription factors GAF and HSF act at distinct regulatory steps to modulate
stress-induced gene activation.
AB - The coordinated regulation of gene expression at the transcriptional level is
fundamental to development and homeostasis. Inducible systems are invaluable when
studying transcription because the regulatory process can be triggered
instantaneously, allowing the tracking of ordered mechanistic events. Here, we
use precision run-on sequencing (PRO-seq) to examine the genome-wide heat shock
(HS) response in Drosophila and the function of two key transcription factors on
the immediate transcription activation or repression of all genes regulated by
HS. We identify the primary HS response genes and the rate-limiting steps in the
transcription cycle that GAGA-associated factor (GAF) and HS factor (HSF)
regulate. We demonstrate that GAF acts upstream of promoter-proximally paused RNA
polymerase II (Pol II) formation (likely at the step of chromatin opening) and
that GAF-facilitated Pol II pausing is critical for HS activation. In contrast,
HSF is dispensable for establishing or maintaining Pol II pausing but is critical
for the release of paused Pol II into the gene body at a subset of highly
activated genes. Additionally, HSF has no detectable role in the rapid HS
repression of thousands of genes.
PMID- 27492369
TI - Relationship Between Antihypertensive Medications and Cognitive Impairment: Part
II. Review of Physiology and Animal Studies.
AB - PURPOSE OF REVIEW: There is an established association between hypertension and
increased risk of poor cognitive performance and dementia including Alzheimer's
disease; however, associations between antihypertensive medications (AHM) and
dementia risk are less clear. An increased interest in AHM has resulted in
expanding publications; however, none of the recent reviews provide comprehensive
review. Our extensive review includes 24 mechanistic animal and human studies
published over the last 5 years assessing relationship between AHM and cognitive
function. RECENT FINDINGS: All classes of AHM showed similar result patterns in
animal studies. The mechanism by which AHM exert their effect was extensively
studied by evaluating well-established pathways of AD disease process, including
amyloid beta (Abeta), vascular, oxidative stress and inflammation pathways, but
only few studies evaluated the blood pressure lowering effect on the AD disease
process. Methodological limitations of the studies prevent comprehensive
conclusions prior to further work evaluating AHM in animals and larger human
observational studies, and selecting those with promising results for future
RCTs.
PMID- 27492370
TI - Relationship Between Antihypertensive Medications and Cognitive Impairment: Part
I. Review of Human Studies and Clinical Trials.
AB - PURPOSE OF REVIEW: There is an established association between hypertension and
increased risk of poor cognitive performance and dementia including Alzheimer's
disease; however, associations between antihypertensive medications (AHMs) and
dementia risk are less consistent. An increased interest in AHM has resulted in
expanding publications; however, none of the recent reviews are comprehensive.
Our extensive review includes 15 observational and randomized controlled trials
(RCTs) published over the last 5 years, assessing the relationship between AHM
and cognitive impairment. RECENT FINDINGS: All classes of AHM showed similar
result patterns in human studies with the majority of study results reporting
point estimates below one and only a small number of studies (N = 15) reporting
statistically significant results in favor of a specific class. Only a small
number of studies reported statistically significant results in favor of a
specific class of AHM. Methodological limitations of the studies prevent
definitive conclusions. Further work is now needed to evaluate the class of AHM
and cognitive outcomes in future RCTs, with a particular focus on the drugs with
the promising results in both animals and human observational studies.
PMID- 27492371
TI - Simulated Microgravity and 3D Culture Enhance Induction, Viability, Proliferation
and Differentiation of Cardiac Progenitors from Human Pluripotent Stem Cells.
AB - Efficient generation of cardiomyocytes from human pluripotent stem cells is
critical for their regenerative applications. Microgravity and 3D culture can
profoundly modulate cell proliferation and survival. Here, we engineered
microscale progenitor cardiac spheres from human pluripotent stem cells and
exposed the spheres to simulated microgravity using a random positioning machine
for 3 days during their differentiation to cardiomyocytes. This process resulted
in the production of highly enriched cardiomyocytes (99% purity) with high
viability (90%) and expected functional properties, with a 1.5 to 4-fold higher
yield of cardiomyocytes from each undifferentiated stem cell as compared with 3D
standard gravity culture. Increased induction, proliferation and viability of
cardiac progenitors as well as up-regulation of genes associated with
proliferation and survival at the early stage of differentiation were observed in
the 3D culture under simulated microgravity. Therefore, a combination of 3D
culture and simulated microgravity can be used to efficiently generate highly
enriched cardiomyocytes.
PMID- 27492372
TI - X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic
Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis.
AB - The X-linked inhibitor of apoptosis (XIAP) deficiency is a primary
immunodeficiency characterized by Epstein-Barr virus (EBV)-driven hemophagocytic
lymphohistiocytosis (HLH), splenomegaly, and colitis. Here, we present, for the
first time, granulomatous hepatitis and granulomatous and lymphocytic
interstitial lung disease (GLILD) as manifestations of XIAP deficiency. We report
successful treatment of GLILD in XIAP deficiency with rituximab and azathioprine
and discuss the role of XIAP deficiency in immune dysregulation.
PMID- 27492373
TI - The invisible basal cell carcinoma: how reflectance confocal microscopy improves
the diagnostic accuracy of clinically unclear facial macules and papules.
AB - Difficult to diagnose and early non-melanoma skin cancer lesions are frequently
seen in daily clinical practice. Besides precancerous lesions such as actinic
keratosis, basal cell carcinomas (BCCs) score the highest frequency in skin
tumors. While infiltrative and nodular BCCs require a surgical treatment with a
significant impact on the patients' quality of life, early and superficial BCCs
might benefit from numerous conservative treatments, such as topical immune
modulators or photodynamic therapy. Dermoscopy has shown a high sensitivity and
specificity in the diagnosis of early BCCs, and non-invasive imaging techniques
like reflectance confocal microscopy (RCM) have proven to be helpful. The aim of
our study was to investigate the importance of RCM in the diagnosis of BCCs with
indistinct clinical and dermoscopic features. We retrospectively examined 27
histologically proven BCCs in which diagnosis was not possible based on naked eye
examination; we separately reviewed clinical, dermoscopic, and confocal
microscopy features and evaluated the lesions meeting the common diagnostic
criteria for BCCs, and our diagnostic confidence. All lesions were clinically
unclear, with no characteristic features suggestive for BCC; dermoscopy showed in
most cases unspecific teleangiectasias (74 %) and micro-erosions (52 %). Confocal
microscopy revealed in most of the cases the presence of specific criteria:
peripheral palisading of the nuclei (89 %), clefting (70 %), stromal reaction (70
%), dark silhouettes (70 %), inflammatory particles (70 %), and tumor islands (67
%). In the absence of significant diagnostic clinical signs and with unclear
dermoscopic features, specific confocal patterns were present in most of the
lesions and enabled a correct diagnosis. In the absence of significant clinical
features of BCC and in the case of uncertain dermoscopy, striking confocal
features are detectable and easy to recognize in most cases. Confocal microscopy
can therefore be instrumentful in the diagnosis of the so-called invisible BCCs.
PMID- 27492374
TI - Polychromatic light-induced osteogenic activity in 2D and 3D cultures.
AB - Photobiomodulation (PBM) has been applied to manipulate cellular responses by
using monochromatic light in different wavelengths from ultraviolet (UV) to
infrared (IR) region. Until now, an effective wavelength has not been revealed to
induce proliferation and/or differentiation of cells. Therefore, in the presented
study, we decided to use a specially designed plasma arc light source providing
wavelengths between 590 and 1500 nm in order to investigate its biomodulatory
effects on chitosan scaffold-supported three-dimensional (3D) cell cultures. For
comparison, two-dimensional (2D) cell cultures were also carried out in tissue
culture polystyrene dishes (TCPS). The results showed that light-induced
temperature rise did not affect cells when the distance between the light source
and the cells was 10 cm and the frequency of administration was daily. Moreover,
light was applied for 5 and 10 min to the cells in TCPS and in chitosan scaffold
groups, respectively. Cell culture studies under static conditions indicated that
polychromatic light significantly stimulated bone nodule formation via the
prolonged cell survival and stimulated differentiation of MC3T3-E1
preosteoblastic cells in both TCPS and chitosan scaffold groups. In conclusion,
specially designed plasma arc light source used in this study induces formation
of bone tissue and so, this light source is proposed as an appropriate system for
in vitro bone tissue engineering applications. Statistical analyses were
performed with one-way ANOVA by using GraphPad Instat software and standard
deviations were calculated by using data of three parallel samples for each
group.
PMID- 27492375
TI - Time-resolved 3D rotational angiography: display of detailed neurovascular
anatomy in patients with intracranial vascular malformations.
AB - PURPOSE: The purpose of this pilot study was to demonstrate the applicability of
time-resolved three-dimensional (3D) reconstructions from 3D digital subtraction
angiography (DSA) rotational angiography (RA) datasets (four-dimensional (4D)
DSA) to provide a more detailed display of the architecture of intracranial
vascular malformations. METHODS: The experimental reconstruction software was
applied to the existing 3D DSA datasets obtained with Siemens Artis zee biplane
neuroangiography equipment. We included 27 patients with clinical indications for
3DRA for preinterventional or preoperative evaluation of intracranial dural
arteriovenous fistulas (dAVFs, n=8) or arteriovenous malformations (AVMs, n=19).
A modified DSA acquisition protocol covering an extended rotation angle of the C
arm of 260 degrees during a scan time of 12 s was used. 4D volumes were
displayed with up to 30 frames/s in a transparent volume rendering (VRT) mode and
time-resolved multiplanar reconstructions (MPRs). Arterial feeders, fistulous
points, or the shunt zone within the AVM nidus and venous drainage patterns as
well as associated aneurysms were assessed after definition of a standardized
evaluation procedure by consensus of two reviewers in comparison with 2D DSA and
conventional 3D reconstructions. RESULTS: In all cases calculation of 4D
reconstructions were technically feasible and evaluable. In two cases image
quality was slightly compromised by movement artifacts. Compared with standard
DSA projection images and 3D reconstructions, 4D VRTs and MPRs were rated
significantly superior to define a proper projection and display of the shunt
zone. In 12 out of 27 cases 4D reconstructions showed details of the
angioarchitecture at the fistulous point or the nidus better than the other
modalities and came close to the quality of superselective angiography. The
efficacy of 3D and 4D applications was equal in the detection of pre- and
intranidal aneurysms. The course of long arterial feeders and draining veins was
difficult to assess on VRTs and MPRs. Especially for dAVFs, 2D DSA was clearly
superior in identifying meningeal feeders. For detecting smaller vessels and for
distinction between angiographic phases, 2D DSA is still considered to be
superior to 4D imaging. Venous drainage was slightly better displayed in 4D
reconstructions. CONCLUSIONS: Time-resolved 3DRA with 4D VRTs and MPRs is
technically feasible and provides a detailed display of the angioarchitecture at
the fistulous point or the nidus. Visualization of all angiographic features
demands additional post-processing. Further standardization of evaluation tools
and studies with blinded independent reviewers are necessary before the new
technique can replace conventional neuroangiographic approaches.
PMID- 27492376
TI - [Prophylactic meshes in the abdominal wall. German version].
AB - BACKGROUND: There is a high incidence of incisional hernias in specific high-risk
patient populations. For these patients, the prophylactic placement of mesh
during closure of the abdominal wall incision has been investigated in several
prospective studies. OBJECTIVE: This article aims to summarize and synthetize the
currently available evidence on prophylactic meshes in a narrative review.
MATERIALS AND METHODS: Systematic reviews were performed on the use of
prophylactic meshes in different indications: midline laparotomies, stoma
reversal wounds, and permanent stoma. RESULTS: High-quality data from randomized
trials shows that prophylactic synthetic non-absorbable mesh implantation is safe
and effective, both in prevention of incisional hernias after midline
laparotomies and during construction of an elective end colostomy. It should be
considered in patients with a high risk for incisional hernia development, such
as those receiving open abdominal aortic aneurysm, obesity, or colorectal cancer
surgery. It is strongly recommended for construction of an elective permanent end
colostomy. For midline laparotomies, both the retromuscular and onlay positions
of a prophylactic mesh seem equally effective and safe. For parastomal hernia
prevention, only the retromuscular prophylactic mesh and its use for end
colostomies has been proven to be effective and safe. No data support the choice
of a biological mesh or a synthetic absorbable mesh over a non-absorbable
synthetic mesh, even in clean-contaminated surgical procedures. No data yet
support the standard use of prophylactic mesh when closing the wound during
closure of a temporary stoma. CONCLUSION: Prophylactic mesh implantation should
be the standard of care during construction of an elective end colostomy and will
become the standard of care for midline laparotomies in patients at high risk of
incisional hernias.
PMID- 27492377
TI - [Impact of perioperative nutritional therapy on risk and complication management
in patients undergoing esophagectomy for cancer].
AB - Esophagectomy is considered to be a high risk procedure regarding postoperative
morbidity and mortality. Therefore, in Germany, these operations are limited to
hospitals fulfilling a minimum quantity. This systematic review focuses on risk
and complication management regarding the impact of perioperative nutritional
therapy, including the recent S3-guideline recommendations and comments of the
German Working Group of Medical Societies (AWMF) which were established with
contributions from the authors.
PMID- 27492378
TI - [Multicystic intra-abdominal mass in a neonate].
PMID- 27492380
TI - Prospective Observational Post-marketing Study of Tafluprost 0.0015%/Timolol 0.5%
Combination Ophthalmic Solution for Glaucoma and Ocular Hypertension: Short-Term
Efficacy and Safety.
AB - INTRODUCTION: The intraocular pressure (IOP)-lowering effect and safety of
tafluprost 0.0015%/timolol maleate 0.5% combination ophthalmic solution (Taf-TFC)
were investigated in a real-world clinical setting. METHODS: A prospective up to
2-year (more than 1 year) observational study has been initiated to collect data
on the IOP, conjunctival hyperemia score, corneal staining score, and adverse
events suffered by patients with glaucoma or ocular hypertension treated at 3
months, and up to 2 years (more than 1 year) after initiating treatment with Taf
TFC. The 3-month findings are reported here. RESULTS: Among 439 patients enrolled
at 100 institutions in Japan, most had normal tension glaucoma (45.3%) or primary
open angle glaucoma (36.0%). Adverse drug reaction (ADR) occurred in 5.01%. The
important ADRs were conjunctival hyperemia (five patients), blepharitis (four
patients), and punctate keratitis (two patients). Serious adverse reactions
occurred in two patients (three events). In 410 patients with data both before
and after treatment, baseline mean IOP was 17.5 +/- 5.0 mmHg, and it was
significantly decreased after 1, 2, and 3 months (all P < 0.05, paired-t test).
IOP was significantly reduced in patients switched to Taf-TFC from either
prostaglandin or beta-blocker monotherapy. IOP also decreased significantly in
patients switched from a prostaglandin/timolol fixed combination, but not in
patients switched from concomitant use of a prostaglandin analog and a beta
blocker. The use of Taf-TFC did not worsen the adherence in most patients.
CONCLUSION: Taf-TFC significantly reduced the IOP in patients with glaucoma or
ocular hypertension treated in daily clinical practice with controllable or
recoverable ADRs in short period. Taf-TFC was effective regardless of treatment
patterns, and particularly, Taf-TFC significantly reduced IOP in cases in which
requiring the second line therapy as insufficient of monotherapy. FUNDING: Santen
Pharmaceutical Co., Ltd., Osaka, Japan.
PMID- 27492379
TI - Trends in major risk factors and mortality from main non-communicable diseases in
Lithuania, 1985-2013.
AB - BACKGROUND: This study aimed to assess the trends in the prevalence and levels of
risk factors and mortality from main non-communicable diseases in the Lithuanian
population aged 45-64 years during 1985 to 2013. METHODS: Data from four general
population surveys conducted between 1985 and 2008 were used. All these surveys
were carried out in Kaunas city and five randomly selected municipalities of
Lithuania. Risk factors measured at each survey included regular smoking,
overweight, obesity, arterial hypertension, and high levels of blood lipids. In
total, data of 10,719 subjects (4,965 men and 5,754 women) aged 45-64 were
analysed. Trends in standardized all-cause mortality and mortality from
cardiovascular disease (CVD), coronary heart disease (CHD), and malignant
neoplasms were estimated for both sexes by joinpoint regression analysis.
RESULTS: In 1985-2013, some favourable trends were observed in the age
standardized mean levels and prevalence of risk factors and mortality from main
non-communicable diseases in the Lithuanian middle-aged population. The mean
values of blood lipids (with the exception of triglycerides) and the prevalence
of dyslipidemias declined. In women, mean levels of systolic blood pressure and
body mass index decreased, while in men, the levels of these factors increased.
The prevalence of arterial hypertension and obesity increased in men. The
proportion of obese women decreased. Smoking prevalence increased in both men and
women. From 2007 to 2008, significant downward trends, which were steeper in
women than in men, were observed in all-cause, CVD, and CHD mortality.
CONCLUSIONS: Despite the favourable changes in some risk factors and mortality
rates, the prevalence of risk factors and mortality from main non-communicable
diseases in Lithuania are still high. This indicates the importance of the
ongoing primary and secondary prevention and optimal treatment of these diseases.
PMID- 27492381
TI - Physical activity after outpatient surgery and enhanced recovery for total knee
arthroplasty.
AB - PURPOSE AND HYPOTHESIS: The purpose of this study was to 'objectively' measure
improvement of physical activity with the use of an activity monitor between
patients who followed an enhanced recovery- or outpatient surgery pathway after
total knee arthroplasty (TKA). It was hypothesized that both pathways will have
comparable physical activity after TKA at 6-week follow-up. METHODS: This
prospective observational comparative case study was designed to investigate
activity parameters (e.g. physical activity, number of steps, sit-stand
transfers) of two different pathways after 6 weeks with the use of a non-invasive
triaxial accelerometer activity monitor. This study included 20 patients with a
mean age of 65.5 years (SD 6.1) undergoing TKA who were allocated to follow one
of the two pathways: enhanced recovery (n = 10) or outpatient surgery (n = 10).
Patients were monitored for 4 days pre-, 4 days during and 4 days after 5 weeks
postoperatively. Patient-reported outcome measures (PROMs) and range of knee
motion were obtained pre- and 6 weeks postoperatively. RESULTS: The activity
parameters recovered steeply during the first 4 postoperative days and continued
to improve within both pathways (n.s.). Preoperative and during the first 4 days
and 5 weeks postoperative, activity parameters were comparable (n.s.) between
both pathways but did not reach preoperative levels of physical activity and
range of motion (n.s.). PROMs improved within each pathway, and no difference
between both pathways was observed (n.s.). CONCLUSIONS: This study demonstrates
that the early physical activity parameters of patients after TKA, following the
outpatient surgery pathway, were similar to patients who followed the standard
enhanced recovery pathway. The activity monitor is an added value for a more
detailed and objective analysis of the physical performance in patients after
TKA. LEVEL OF EVIDENCE: III.
PMID- 27492382
TI - The prevalence of proximal hamstring pathology on MRI in the asymptomatic
population.
AB - PURPOSE: Injury to the proximal hamstring complex (PHC) is becoming more
frequently diagnosed. Patients attending our tertiary referral centre
demonstrated 'pathological changes' in the unaffected normal contralateral PHC on
MRI. The prevalence of PHC pathology, however, has not been previously documented
in the literature in asymptomatic subjects. It is the hypothesis of this study
that the natural history of asymptomatic pathological change on MRI in the PHC is
not clear. The aim is to quantify the natural history of PHC degeneration.
METHOD: Two hundred and fifty-three consecutive patients with an asymptomatic PHC
were reviewed retrospectively between 2009 and 2010. The PHC was assessed in
multiple MRI planes by a specialist musculoskeletal consultant radiologist.
RESULTS: Five hundred and six proximal hamstrings complexes were reviewed. Eighty
nine patients (35 %) were radiological normal both sides, median age 51 years
(range 13-88). Thirty-four patients (13 %) had unilateral pathology, median age
55 years (range 25-89). Of these, 3 patients (1 %) had presence of a complete
tear, median age 81 years (range 72-87). Sixteen patients (7 %) had tendinosis,
median age 60 years (range 37-78). Fifteen patients (6 %) had a unilateral
partial tear, median age 57 years (range 35-78). One hundred and thirty patients
(52 %) had bilateral pathology, median age 65 years (range 25-89). Fifty-three
patients (21 %) had the presence of bilateral tendinopathy alone, median age 56
years (range 25-89). Twenty-seven patients (11 %) had a partial tear on one side
and tendinosis on the other, median age 68 years (range 38-89). Thirty-nine
patients (15 %) had evidence of bilateral partial tears, median age 63 years
(range 36-89), with 52 % demonstrating a torn conjoined and semi-membranosus
tendon. The remaining 48 % had either an isolated tear of the conjoined or the
semi-membranosus (the more commonly injured tendon 74 % of the time). Four
patients (2 %) had bilateral complete ruptures with a median age of 68 years
(range 59-78). Six patients (2 %) had a complete tear on one side and a partial
tear on the other, median age 68 years (range 34-83). One patient had a complete
tear on one side and tendinosis on the other, age 81 years. CONCLUSION: There is
a higher prevalence of pathology in the asymptomatic population, 15 % have
bilateral partial tears, and 2 % have bilateral complete tears. The semi
membranosus being the most affected, this may help clinically stratify the need
for surgical intervention. LEVEL OF EVIDENCE: I.
PMID- 27492383
TI - Anterior hip capsuloligamentous reconstruction with Achilles allograft following
gross hip instability post-arthroscopy.
AB - The increasing use of hip arthroscopy has led to further development in our
understanding of hip anatomy and potential post-operative complications.
Iatrogenic gross hip instability following hip arthroscopy is a concerning
complication described in recent orthopaedic literature. Post-arthroscopy hip
instability is thought to be multifactorial, related to a variety of patient,
surgical and post-operative factors. Given its infrequency, there is scarcity of
literature describing appropriate surgical management and operative technique for
addressing this instability. This study reports a case of gross hip instability
following hip arthroscopy, describing a novel technique of management through
anterior hip capsuloligamentous reconstruction with Achilles tendon allograft.
Level of evidence V, Case Study.
PMID- 27492384
TI - The accuracy of bony resection from patient-specific guides during total knee
arthroplasty.
AB - PURPOSE: In patient-specifically instrumented (PSI) total knee arthroplasty, the
correlation between the pre-operative surgical plan, accuracy of the cutting
block, and intra-operative resection size is unclear. The aim of this study was
to evaluate the ability to accurately execute the PSI surgical plan and to add to
the merging information with respect to this technology with the hypothesis that
the PSI blocks would demonstrate good accuracy with regard to the bony thickness
of the resections. METHODS: One hundred and thirty TKAs using PSI (MRI/long-leg
radiographs) were retrospectively analysed. All surgeries were conducted via
similar surgical approach and technique, with resection performed after guide
placement and alignment assessment. The bony cut thicknesses of the medial (MTP)
and lateral tibial plateau (LTP), distal medial (DM), distal lateral (DL),
posterior medial (PM) and posterior lateral (PL) femur were measured with a
vernier calliper. The measured resection thickness was subtracted from the
planned resection. Errors were defined as <=1.5 mm (acceptable), 1.5-2.5 mm
(borderline), and >2.5 mm (outliers). RESULTS: Overall, 81 (62.3 %) of the knees
were free of outliers. The distal femur cut had the highest proportion of
acceptable cut error with 209 of 260 total cuts acceptable (80.4 %). The tibial
cuts had the lowest proportion of "acceptable" cuts (68.9 %). Tibial cuts had
more outliers (33 of 260 cuts, 12.7 %) than the femur (39 of 520 cuts, 7.5 %) (p
= 0.01). Pre-operative varus (n = 97) and valgus (n = 33) deformities
demonstrated 7.7 % (45/482) and 13.6 % (27/198) of cuts which were outliers,
respectively (p = 0.01). CONCLUSION: PSI showed only fair to moderate accuracy
with 62.3 % of the knees presenting no outliers. The tibia cutting guide was less
accurate than the femur. Specific attention is needed when cutting the tibia and
in correction of valgus deformity. Moreover, intra-operative verifying
measurements can provide feedback to the accuracy of the surgical plan. LEVEL OF
EVIDENCE: IV, case series with no comparison group.
PMID- 27492385
TI - Willingness to participate in health research: Tunisian survey.
AB - BACKGROUND: Few studies have identified the willingness rate of developing
countries population to be enrolled in clinical trials. METHODS: All participants
including patients (n = 612), healthy volunteers (n = 354) and doctors (n = 134)
completed a questionnaire to examine factors affecting the consent to participate
in medical research. RESULTS: Overall, 80 % of the included population agree to
participate in health research. This rate was lower for trials dealing with life
threatening diseases (38 %). Altruism and perceived risk of harm were the main
reason to respectively accept or refuse to participate in clinical trials.
Factors significantly associated with willingness were: age <40 years (Odds Ratio
(OR) 1.6 [95 % Confidence Interval (CI) 1.2-2.1]) and prior history of blood
donation (OR 2.4 [95 % CI 1.7-3.5]). CONCLUSION: Most participants expressed
their willingness to be included in medical research especially if they are young
or if they have history of blood donation. However, consent to participate is low
when medical research required acute care.
PMID- 27492387
TI - Prescription drug misuse in Europe is higher than previously thought.
PMID- 27492386
TI - Microbiota and chronic inflammatory arthritis: an interwoven link.
AB - BACKGROUND: Only recently, the scientific community gained insights on the
importance of the intestinal resident flora for the host's health and disease.
Gut microbiota in fact plays a crucial role in modulating innate and acquired
immune responses and thus interferes with the fragile balance inflammation versus
tolerance. MAIN BODY: Correlations between gut bacteria composition and the
severity of inflammation have been studied in inflammatory bowel diseases. More
recently similar alterations in the gut microbiota have been reported in patients
with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of
evidence evokes a pathogenic role for the altered oral microbiota in disease
development and course. In the context of dysbiosis it is also important to
remember that different environmental factors like stress, smoke and dietary
components can induce strong bacterial changes and consequent exposure of the
intestinal epithelium to a variety of different metabolites, many of which have
an unknown function. In this perspective, and in complex disorders like
autoimmune diseases, not only the genetic makeup, sex and immunologic context of
the individual but also the structure of his microbial community should be taken
into account. CONCLUSIONS: Here we provide a review of the role of the microbiota
in the onset, severity and progression of chronic inflammatory arthritis as well
as its impact on the therapeutic management of these patients. Furthermore we
point-out the complex interwoven link between gut-joint-brain and immune system
by reviewing the most recent data on the literature on the importance of
environmental factors such as diet, smoke and stress.
PMID- 27492389
TI - Surgical outcome of the shunt: 15-year experience in a single institution.
AB - PURPOSE: Surgical outcome after shunt insertion in pediatric hydrocephalus can
vary greatly. Although first shunt survival rates and complications have been
studied by several teams, much less is known about survival and complications of
subsequent systems. The goals of this study were to evaluate the surgical outcome
in a series of pediatric patients followed for a long time and establish the
differences between first and subsequent extracranial shunt survival and
complications. METHODS: We undertook a retrospective study in pediatric patients
treated with ventriculoperitoneal shunts between 2000 and 2015 at our
institution. Surgical outcome was assessed, and different shunt survival curves
were studied with Kaplan-Meier. Complications related to each shunt failure were
examined and compared. RESULTS: A total of 166 patients underwent 425 procedures,
with a mean follow-up period of 93 months. The median number of shunt revision
surgeries was 2. Shunt survival rates were better with the first shunt compared
to those with the subsequent shunts. The main complication necessitating system
revision surgery was overdrainage, the frequency of proximal and distal
dysfunctions was similar in all the shunt failures, and isolated ventricle and
infection were more frequent in younger patients. Shunt-related infections
accounted for 7 % of the procedures, and the shunt independence rate was 10 %.
CONCLUSIONS: The frequency of complications related to shunt failure in pediatric
patients changes during follow-up. A strict protocol of overdrainage detection
and active treatment could explain the need for repeat surgeries and the
progressively shorter shunt survival time in our series.
PMID- 27492390
TI - Sonography and Transthoracic Echocardiography for Diagnosis of Systemic
Cardiovascular Metastatic Tumor Thrombi.
AB - Sonography and transthoracic echocardiography (TTE) are seldom used for
assessment of metastatic tumor thrombi in the cardiovascular system in routine
clinical practice. We performed this retrospective study to evaluate the
combination of sonography with TTE for diagnosis of metastatic tumor thrombi in
heart and systemic vessels. Vascular, abdominal, pelvic, and small-part
sonography was applied in 18 patients, and TTE was conducted simultaneously in 14
patients. Tumor thrombi invaded into the inferior vena cava system in 12
patients, superior vena cava system in 5 patients, and aorta in 1 patient; they
extended to the right cardiac chambers in 11 patients. Six patients had diagnoses
by pathologic examination. The primary neoplasms were identified by conventional
imaging in 17 patients. The morphologic and echogenic characteristics of the
tumor thrombi were diverse and depended on their original tumors. The thrombi
were either contiguous or discrete from the original tumors. The neoplastic
vascularity of the thrombi and the invasive extension were the primary
characteristics that distinguished them from bland thrombi. Simultaneous
application of sonography and TTE is a feasible way to comprehensively evaluate
cardiovascular metastatic tumor thrombi in most patients.
PMID- 27492388
TI - Feasibility, tolerability and safety of pediatric hyperpolarized 129Xe magnetic
resonance imaging in healthy volunteers and children with cystic fibrosis.
AB - BACKGROUND: Hyperpolarized 129Xe is a promising contrast agent for MRI of
pediatric lung function, but its safety and tolerability in children have not
been rigorously assessed. OBJECTIVE: To assess the feasibility, safety and
tolerability of hyperpolarized 129Xe gas as an inhaled contrast agent for
pediatric pulmonary MRI in healthy control subjects and in children with cystic
fibrosis. MATERIALS AND METHODS: Seventeen healthy control subjects (ages 6-15
years, 11 boys) and 11 children with cystic fibrosis (ages 8-16 years, 4 boys)
underwent 129Xe MRI, receiving up to three doses of 129Xe gas prepared by either
a commercially available or a homebuilt 129Xe polarizer. Subject heart rate and
SpO2 were monitored for 2 min post inhalation and compared to resting baseline
values. Adverse events were reported via follow-up phone call at days 1 and 30
(range +/-7 days) post-MRI. RESULTS: All children tolerated multiple doses of
129Xe, and no children withdrew from the study. Relative to baseline, most
children who received a full dose of gas for imaging (10 of 12 controls and 8 of
11 children with cystic fibrosis) experienced a nadir in SpO2 (mean -6.0 +/-
standard deviation 7.2%, P<=0.001); however within 2 min post inhalation SpO2
values showed no significant difference from baseline (P=0.11). There was a
slight elevation in heart rate (mean +6.6 +/- 13.9 beats per minute [bpm],
P=0.021), which returned from baseline within 2 min post inhalation (P=0.35).
Brief side effects related to the anesthetic properties of xenon were mild and
quickly resolved without intervention. No serious or severe adverse events were
observed; in total, four minor adverse events (14.3%) were reported following
129Xe MRI, but all were deemed unrelated to the study. CONCLUSION: The
feasibility, safety and tolerability of 129Xe MRI has been assessed in a small
group of children as young as 6 years. SpO2 changes were consistent with the
expected physiological effects of a short anoxic breath-hold, and other mild side
effects were consistent with the known anesthetic properties of xenon and with
previous safety assessments of 129Xe MRI in adults. Hyperpolarized 129Xe is a
safe and well-tolerated inhaled contrast agent for pulmonary MR imaging in
healthy children and in children with cystic fibrosis who have mild to moderate
lung disease.
PMID- 27492391
TI - Klippel-Trenaunay Syndrome: Need for Careful Clinical Classification.
AB - Klippel-Trenaunay syndrome (KTS) is a rare congenital malformation characterized
by a triad of clinical presentations: (1) capillary malformations manifesting as
a "port wine stain"; (2) limb hypertrophy; and (3) venous varicosities. It is
distinguished from Parkes-Weber syndrome by the absence of substantial
arteriovenous shunting. Due to the clinical implications of an arteriovenous
fistula, differentiation between the two syndromes is important, as the prognosis
and treatment greatly differ. We present a series of 5 cases of suspected KTS,
while emphasizing the difficulties in distinguishing KTS from Parkes-Weber
syndrome without diagnostic imaging and underscoring the importance of accurately
classifying patients with the appropriate syndrome.
PMID- 27492392
TI - Is Brachial Artery Blood Flow Measured by Sonography During Early Postoperative
Periods Predictive of Arteriovenous Fistula Failure in Hemodialysis Patients?
AB - OBJECTIVES: The aim of our study was to determine a brachial artery blood flow
level measured by sonography during early postoperative periods that is
predictive of arteriovenous fistula failure in hemodialysis patients. METHODS:
Doppler sonography was used to estimate the blood flow in the brachial artery of
103 patients at 1 and 14 days after arteriovenous fistula creation. The
performance of brachial artery blood flow during early postoperative periods for
predicting fistula failure was evaluated, and optimal cutoff values were
determined. RESULTS: During a 6-month follow-up, 85 fistulas were classified as
mature, and 18 were classified as failures. The reproducibility of blood flow
measurements in the brachial artery was good (intraclass correlation coefficient,
0.912). The blood flow in the failure group was significantly lower than that in
the mature group at both 1 and 14 days after fistula creation (P < .05). During
the first 2 postoperative weeks, the blood flow increased by 40.7% in the failure
group versus 78.3% in the mature group. The areas under the receiver operating
characteristic curves of brachial artery blood flow for predicting failure were
0.77 (95% confidence interval, 0.66-0.87; optimal cutoff value, 310 mL/min)at 1
day and 0.91 (95% confidence interval, 0.83-0.99; 413 mL/min) at 14 days after
fistula creation. CONCLUSIONS: Brachial artery blood flow measured by sonography
during early postoperative periods may be predictive of forearm fistula failure.
Blood flow of less than 310 mL/min at 1 day and 413 mL/min at 14 days after
fistula creation may indicate a risk of failure to mature.
PMID- 27492393
TI - Stenosis in Middle Cerebral Artery Duplication: Assessment With Transcranial
Color-Coded Duplex Sonography.
AB - Duplication of the middle cerebral artery is an unusual anatomic variant.
Stenosis of one of its branches can be an exceptional cause of stroke and is very
difficult to diagnose with transcranial duplex sonography. We report 2 patients
with duplication of the middle cerebral artery in whom stenosis of one of its
branches led to ischemic stroke and describe the sonographic findings in
comparison to other neuroimaging modalities. These cases highlight the utility of
adding a coronal insonation plane on top of the traditional axial plane to avoid
identification pitfalls in patients with anatomic variants.
PMID- 27492394
TI - Three-Dimensional Color/Power Doppler Sonography and HD live Silhouette Mode for
Diagnosis of Molar Pregnancy.
AB - We present our experience of using new 3-dimensional color/power Doppler
sonography (HDliveFlow; GE Healthcare Japan, Tokyo, Japan) with the HD live
silhouette mode for diagnosing complete molar pregnancy in the first trimester
and differentiating it from missed abortion with hydropic degeneration. In the
case of a complete mole, color Doppler sonography showed numerous vesicles
without blood vessels, whereas HDliveFlow with the HD live silhouette mode
clearly depicted these vesicles forming a mass with the clear demarcation of its
edges and showed no blood flow inside the mass. In contrast to the hydropic
abortion, which appeared as some vesicles with many blood vessels around them on
color Doppler sonography, HDliveFlow with the HD live silhouette mode showed some
vesicles embedded within the abundant blood vessels. The spatial relationship
between the vesicles and surrounding highly vascularized uterus could be shown on
HDliveFlow with the HD live silhouette mode. This technique might be beneficial
as an additional diagnostic tool along with conventional color/power Doppler
sonography, and it facilitates the early discrimination of these cases in the
first trimester of pregnancy.
PMID- 27492395
TI - Secondary structure and (1)H, (13)C and (15)N resonance assignments of Skint-1: a
selecting ligand for a murine gammadelta T cell subset implicated in tumour
suppression.
AB - A study describing the (1)H, (13)C and (15)N backbone and side chain chemical
shift assignments and secondary structure of Skint-1 a prototypic member of a
family of mouse genes, of which Skint-1 is involved in the development of the
dendritic epidermal T cell (DETC) subset of gammadelta T cells.
PMID- 27492396
TI - Economic evaluation of pegylated interferon plus ribavirin for treatment of
chronic hepatitis C in Thailand: genotype 1 and 6.
AB - BACKGROUND: Pegylated interferon alpha 2a, alpha 2b and ribavirin have been
included to the National List of Essential Medicines (NLEM) for treatment of only
chronic hepatitis C genotypes 2 and 3 in Thailand. This reimbursement policy has
not covered for other genotypes of hepatitis C virus infection (HCV) especially
for genotypes 1 and 6 that account for 30-50 % of all HCV infection in Thailand.
Therefore, this research determined whether pegylated interferon alpha 2a or
alpha 2b plus ribavirin is more cost-effective than a palliative care for
treatment of HCV genotype 1 and 6 in Thailand. METHODS: A cost-utility analysis
using a model-based economic evaluation was conducted based on a societal
perspective. A Markov model was developed to estimate costs and quality-adjusted
life years (QALYs) comparing between the combination of pegylated interferon
alpha 2a or alpha 2b and ribavirin with a usual palliative care for genotype 1
and 6 HCV patients. Health-state transition probabilities, virological responses,
and utility values were obtained from published literatures. Direct medical and
direct non-medical costs were included and retrieved from published articles and
Thai Standard Cost List for Health Technology Assessment. The incremental cost
effectiveness ratio (ICER) was presented as costs in Thai baht per QALY gained.
RESULTS: HCV treatment with pegylated interferon alpha 2a or alpha 2b plus
ribavirin was dominant or cost-saving in Thailand compared to a palliative care.
The ICER value was negative with lower in total costs (peg 2a- 747,718vs. peg 2b-
819,921 vs. palliative care- 1,169,121 Thai baht) and more in QALYs (peg 2a-
13.44 vs. peg 2b- 13.14 vs. palliative care- 11.63 years) both in HCV genotypes 1
and 6. CONCLUSION: As cost-saving results, the Subcommittee for Development of
the NLEM decided to include both pegylated interferon alpha 2a and alpha 2b into
the NLEM for treatment of HCV genotype 1 and 6 recently. Economic evaluation for
these current drugs can be further applied to other novel medications for HCV
treatment.
PMID- 27492397
TI - A Method for Quantitative Evaluation of the Results of Postural Tests.
AB - A method for quantitative evaluation of the results of postural tests is
proposed. The method is based on contact-free measurements of 3D coordinates of
body point movements. The result can serve as an integral test based on the
Mahalanobis distance.
PMID- 27492399
TI - Comparative Culturing of 3T3 Swiss J2 Mouse Embryo Fibroblasts on Modified
Chitosan Matrices.
AB - Comparative culturing of mouse embryo fibroblasts on chitosan matrices and
culture plastic was carried out. During the first 2 h of culturing (lag phase),
cell adhesion to chitosan and chitosan-gelatin matrices was 20-30% higher than
adhesion to culture plastic (control). During the stationary phase, 80% cells
adhered to chitosan matrices (vs. 60% in the control). Cell culturing on chitosan
matrices was carried out without medium replacement with fresh portions. The
cells remained viable within 5 days of culturing. Cell death phase was observed
on day 6 of culturing on chitosan matrices: cell adhesion dropped to 50%.
Culturing on culture plastic was carried out with daily medium replacement with a
fresh portion. Cell death phase (50% decrease in the number of adherent cell)
under these condition was observed on day 5. It seems that the observed effect
was a result of contact interactions of cell integrins and chitosan ligands,
modulation of transmembrane signal, eventually modifying the expression of cell
genes. This effect can be required in regenerative medicine for production of
primary cell culture.
PMID- 27492398
TI - Analysis of Polymorphism of Angiotensin System Genes (ACE, AGTR1, and AGT) and
Gene ITGB3 in Patients with Arterial Hypertension in Combination with Metabolic
Syndrome.
AB - Changes in the frequencies of genotypes and mutant alleles of ACE, AGTR1, AGT,
and ITGB3 genes were analyzed in patients with arterial hypertension coupled with
metabolic syndrome (N=15) and compared with population data and corresponding
parameters in patients with isolated hypertension (N=15). Increased frequency of
genotype ID of ACE gene (hypertension predictor) was confirmed for both groups.
In case of isolated hypertension, M235M genotype (gene AGT) was more frequent, in
case of hypertension combined with metabolic syndrome, the frequency of genotypes
A1166C and C1166C of the gene AGTR1 was higher in comparison with population
data. Comparison of mutant allele frequencies in the two groups showed that at
the 90% significance level allele T of the AGT gene was more frequent in
hypertension coupled with metabolic syndrome (OR=1.26) and genotype A1166A of the
AGTR1 gene was more frequent in the group with isolated hypertension.
PMID- 27492400
TI - On Methods for the Analysis of Indefinite Stimuli Perception Characteristics: an
fMRT Study of Gender-Specific Differences.
AB - Comparative identification of cerebral regions activated in men and women during
perception of indefinite images was carried out by fMRT and psychological
testing. Nine men and nine women aged 20-26 years took part in the study. The
volunteers examined simple geometric figures, slightly structurized images
(tables from Rorschach's test), and images of impossible figures. Activation in
the cerebellum and visual cortex (bilateral) was more pronounced in women in
response to all types of images and less so in the right G. temporalis medius.
The right frontal regions (G. precentralis, G. frontalis superior, G. frontalis
medius) were also stronger activated in women in response to indefinite stimuli.
PMID- 27492401
TI - Reflection of the State of Hunger in Impulse Activity of Nose Wing Muscles and
Upper Esophageal Sphincter during Search behavior in Rabbits.
AB - Reflection of the state of hunger in impulse activity of nose wing muscles and
upper esophageal sphincter muscles was studied in chronic experiments on rabbits
subjected to 24-h food deprivation in the absence of locomotion and during search
behavior. In the absence of apparent behavioral activity, including sniffing,
alai nasi muscles of hungry rabbits constantly generated bursts of action
potentials synchronous with breathing, while upper esophageal sphincter muscles
exhibited regular aperiodic low-amplitude impulse activity of tonic type. Latent
form of food motivation was reflected in the structure of temporal organization
of impulse activity of alai nasi muscles in the form of bimodal distribution of
interpulse intervals and in temporal structure of impulse activity of upper
esophageal sphincter muscles in the form of monomodal distribution. The latent
form of food motivation was manifested in the structure of temporal organization
of periods of the action potentials burst-like rhythm, generated by alai nasi
muscles, in the form of monomodal distribution, characterized by a high degree of
dispersion of respiratory cycle periods. In the absence of physical activity
hungry animals sporadically exhibited sniffing activity, manifested in the change
from the burst-like impulse activity of alai nasi muscles to the single-burst
activity type with bimodal distribution of interpulse intervals and monomodal
distribution of the burst-like action potentials rhythm periods, the maximum of
which was shifted towards lower values, which was the cause of increased
respiratory rate. At the same time, the monomodal temporal structure of impulse
activity of the upper esophageal sphincter muscles was not changed. With
increasing food motivation in the process of search behavior temporal structure
of periods of the burst-like action potentials rhythm, generated by alai nasi
muscles, became similar to that observed during sniffing, not accompanied by
animal's locomotion, which is typical for the increased respiratory rhythm
frequency. Increased hunger motivation was reflected in the temporal structure of
impulse activity of upper esophageal sphincter muscles in the form of a shift to
lower values of the maximum of monomodal distribution of interpulse intervals on
the histogram, resulting in higher impulse activity frequency. The simultaneous
increase in the frequency of action potentials bursts generation by alai nasi
muscles and regular impulse activity of upper esophageal sphincter muscles is a
reliable criterion for enhanced food motivation during search behavior in
rabbits.
PMID- 27492402
TI - Effect of Contamination with Perennial Permafrost Microorganisms on the Outcome
of Closed Brain Neurotrauma.
AB - We studied the effect of contamination with Bacillus genus microorganisms
isolated from perennial permafrost samples on the outcome of closed brain
neurotrauma in Wistar rats. It was found that contamination with different
Bacillus strains produced different effects on the mortality of experimental
animals with closed neurotrauma. The complex of metabolites from strain Ch2/9 -
Bacillus spp. (pumilus) produced a protective effect in experimental closed brain
neurotrauma.
PMID- 27492403
TI - Dynamics of Erythropoiesis in Erythroblastic Islands in the Bone Marrow in
Experimental Benzene-Induced Anemia.
AB - In 14 days after triple subcutaneous injection of benzene to rats in a dose of
0.05 ml/100 g body weight, the number of erythroblastic islands in the bone
marrow 2-fold decreased, de novo erythropoiesis ceased, de repeto erythropoiesis
slowed down, and the number of lymphoid cells contacting with erythroblastic
islands decreased. By day 56 of the experiment, proliferation of erythroid cells
in the bone marrow start to recover due to erythropoiesis reconstitution, but the
number of reticulocytes in the blood remained low. Analysis of phagocytic ability
of macrophages in the erythroblastic islands showed that the intensity of
phagocytosis of latex particles in mature islands decreased, which could affect
denucleation of oxyphilic erythroblasts.
PMID- 27492404
TI - Population Polymorphism of IFNL3 and IFNL4 Genes of Type 3 Interferon Associated
with Spontaneous Clearance of Hepatitis C Virus in Representatives of Caucasian
and Mongoloid Races.
AB - The frequency of single nucleotide polymorphisms of IFNL3 gene (rsl12979860 and
rs8099917) and dinucleotide polymorphism of IFNL4 gene (ss469415590) were
estimated in healthy inhabitants of Mongolia and Irkutsk regions taking into
account their races. Population and genetic studies were performed in 1520
conventionally healthy volunteers (blood donors), representatives of Caucasian
and Mongoloid races. Significant race-related differences in the incidence of
IFNL3 and IFNL4 gene polymorphisms associated with spontaneous clearance of
hepatitis C virus were found in healthy volunteers.
PMID- 27492405
TI - Circadian Rhythms of Carbohydrate Metabolism in Women with Different Types of
Obesity.
AB - Blood levels of glucose and immunoreactive insulin were assessed in women with
android and gynoid types of obesity or normal body weight (control group) in the
dynamics of oral glucose tolerance test in the morning and in the evening. In the
control group, the mean concentrations of glucose and immunoreactive insulin were
significantly higher in the evening at all test terms (0, 60 and 120 min), which
is indicative of physiological insulin resistance in the evening. In the group of
women with gynoid obesity, no difference in the levels of glucose and
immunoreactive insulin was revealed in the morning and evening tests, but in the
evening tests, glucose (60 and 120 min) and immunoreactive insulin (120 min)
levels were lower than in the control group. In the group of women with android
obesity, the evening glucose level on minutes 60 and 120 of the test was higher
than in the morning, but immunoreactive insulin did not vary throughout the day
and on minutes 60 and 120 it surpassed the corresponding parameter in the control
group by 2-4 times. In case of gynoid obesity, glucose load was followed by
hyperinsulinemia and hypoglycemia; in android obesity, it was followed by
hyperinsulinemia, hyperglycemia, and insulin resistance irrespective of the time
of the day.
PMID- 27492406
TI - Effect of Opiate Receptors Blockade on Microbicidal Potential and Production of
IL-1beta, TNFalpha, and IL-10 by Peritoneal Macrophages under Stress Conditions.
AB - Rotation stress activated spontaneous and zymosan-induced ROS production. In
animals receiving naloxone against the background of rotation stress, ROS
production did not increase. Immobilization stress did not change the intensity
of spontaneous and zymosan-induced ROS production, but inhibited stimulated ROS
production against the background of naloxone treatment. Rotation produced a
naloxone-independent inhibitory effect on spontaneous and stimulated IL-1beta and
TNFalpha production by macrophages and naloxone-dependent stimulating effect on
spontaneous IL-10 production. Rotation stress did not modulate stimulated IL-10
production. In case of immobilization stress, decreased IL-1beta and TNFalpha
production was observed in mice exposed to stress under conditions of opiate
receptors blockade; IL-10 production was not affected by immobilization stress.
Both types of stress significantly increased plasma corticosterone levels, while
naloxone had no effect on corticosterone production.
PMID- 27492407
TI - Drugs Related to Oropharyngeal Dysphagia in Older People.
AB - Scientific evidence on the impact of medication on the physiology of swallowing
is scarce and mainly based on clinical case reports. To evaluate the association
between oropharyngeal dysphagia (OD) and chronic exposure to medication in older
patients admitted to the acute geriatric unit (AGU) of a secondary hospital, we
performed a retrospective cross-sectional study of 966 patients admitted to an
AGU from 2008 to 2011. We reviewed (a) diagnosis of OD (assessed with the volume
viscosity swallow test, V- VST); (b) chronic patient medication classified by
anatomical, therapeutic, chemical codes; and (c) demographic and clinical data. A
univariate analysis was performed to determine which medications were associated
with OD. A multivariate analysis adjusting for confounding clinical factors was
performed to identify which of those medications were independently associated
with OD. The age of patients included was 85.3 +/- 6.37 years and 59.4 % were
women. A total of 41.9 % presented OD. We found a possible protective effect of
beta blocking agents on OD after the multivariate analysis (OR 0.54, 95 % CI 0.35
0.85). None of the categories of drugs was associated with an altered swallowing
function after adjusting for confounding variables. The present study is the
first one to widely investigate the association between drugs and OD, increasing
understanding of their association. The role of beta blockers in OD needs to be
further studied as their potentially beneficial effects on the swallowing
function in older patients could help to prevent complications.
PMID- 27492410
TI - What Will It Take to Reduce the App Gap?
PMID- 27492409
TI - Refined stratified-worm-burden models that incorporate specific biological
features of human and snail hosts provide better estimates of Schistosoma
diagnosis, transmission, and control.
AB - BACKGROUND: Schistosoma parasites sustain a complex transmission process that
cycles between a definitive human host, two free-swimming larval stages, and an
intermediate snail host. Multiple factors modify their transmission and affect
their control, including heterogeneity in host populations and environment, the
aggregated distribution of human worm burdens, and features of parasite
reproduction and host snail biology. Because these factors serve to enhance local
transmission, their inclusion is important in attempting accurate quantitative
prediction of the outcomes of schistosomiasis control programs. However, their
inclusion raises many mathematical and computational challenges. To address
these, we have recently developed a tractable stratified worm burden (SWB) model
that occupies an intermediate place between simpler deterministic mean worm
burden models and the very computationally-intensive, autonomous agent models.
METHODS: To refine the accuracy of model predictions, we modified an earlier
version of the SWB by incorporating factors representing essential in-host
biology (parasite mating, aggregation, density-dependent fecundity, and random
egg-release) into demographically structured host communities. We also revised
the snail component of the transmission model to reflect a saturable form of
human-to-snail transmission. The new model allowed us to realistically simulate
overdispersed egg-test results observed in individual-level field data. We
further developed a Bayesian-type calibration methodology that accounted for
model and data uncertainties. RESULTS: The new model methodology was applied to
multi-year, individual-level field data on S. haematobium infections in coastal
Kenya. We successfully derived age-specific estimates of worm burden
distributions and worm fecundity and crowding functions for children and adults.
Estimates from the new SWB model were compared with those from the older, simpler
SWB with some substantial differences noted. We validated our new SWB estimates
in prediction of drug treatment-based control outcomes for a typical Kenyan
community. CONCLUSIONS: The new version of the SWB model provides a better tool
to predict the outcomes of ongoing schistosomiasis control programs. It reflects
parasite features that augment and perpetuate transmission, while it also readily
incorporates differences in diagnostic testing and human sub-population
differences in treatment coverage. Once extended to other Schistosoma species and
transmission environments, it will provide a useful and efficient tool for
planning control and elimination strategies.
PMID- 27492411
TI - Executive Summary of the Key Concepts.
PMID- 27492408
TI - Effects of Change in Tongue Pressure and Salivary Flow Rate on Swallow Efficiency
Following Chemoradiation Treatment for Head and Neck Cancer.
AB - Patients treated with chemoradiation for head and neck cancer frequently develop
dysphagia. Tissue damage to the oral tongue causing weakness along with decreases
in saliva production may contribute to dysphagia. Yet, effects of these variables
on swallowing-related measures are unclear. The purpose of this study was (1) to
determine effects of chemoradiation on tongue pressures, as a surrogate for
strength, and salivary flow rates and (2) to elucidate relationships among tongue
pressures, saliva production, and swallowing efficiency by bolus type. Twenty-one
patients with head and neck cancer treated with chemoradiation were assessed
before and after treatment and matched with 21 healthy control participants who
did not receive chemoradiation. Each participant was given a questionnaire to
rate dysphagia symptoms. Videofluoroscopic Evaluation of Swallowing (VFES) was
used to determine swallowing efficiency; the Saxon test measured salivary flow
rate; and the Iowa Oral Performance Instrument (IOPI) was used for oral tongue
maximum and endurance measures. Results revealed significantly lower tongue
endurance measures for patients post-treatment as compared to controls (p =
.012). Salivary flow rates also were lower compared to pre-treatment (p = .000)
and controls (p = .000). Simple linear regression analyses showed that change in
salivary flow rate was predictive of change in swallow efficiency measures from
pre- to post-treatment for 1 mL thin liquid (p = .017), 3 mL nectar-thick liquid
(p = .026), and 3 mL standard barium pudding (p = .011) boluses. Based on these
findings, it appears that chemoradiation treatment affects tongue endurance and
salivary flow rate, and these changes may impact swallow efficiency. These
factors should be considered when planning treatment for dysphagia.
PMID- 27492412
TI - Could Designing a Hospital Like a Medical Device Contribute to Patient Safety?
PMID- 27492413
TI - Patient Safety: A Priority for Healthcare and for Healthcare Design.
PMID- 27492414
TI - People Want to Know.
PMID- 27492415
TI - Integrated Framework for Patient Safety and Energy Efficiency in Healthcare
Facilities Retrofit Projects.
AB - There is a growing focus on enhancing energy efficiency in healthcare facilities,
many of which are decades old. Since replacement of all aging healthcare
facilities is not economically feasible, the retrofitting of these facilities is
an appropriate path, which also provides an opportunity to incorporate energy
efficiency measures. In undertaking energy efficiency retrofits, it is vital that
the safety of the patients in these facilities is maintained or enhanced.
However, the interactions between patient safety and energy efficiency have not
been adequately addressed to realize the full benefits of retrofitting healthcare
facilities. To address this, an innovative integrated framework, the Patient
Safety and Energy Efficiency (PATSiE) framework, was developed to simultaneously
enhance patient safety and energy efficiency. The framework includes a step -: by
-: step procedure for enhancing both patient safety and energy efficiency. It
provides a structured overview of the different stages involved in retrofitting
healthcare facilities and improves understanding of the intricacies associated
with integrating patient safety improvements with energy efficiency enhancements.
Evaluation of the PATSiE framework was conducted through focus groups with the
key stakeholders in two case study healthcare facilities. The feedback from these
stakeholders was generally positive, as they considered the framework useful and
applicable to retrofit projects in the healthcare industry.
PMID- 27492417
TI - Genomic and functional features of the biosurfactant producing Bacillus sp. AM13.
AB - Genomic studies provide deeper insights into secondary metabolites produced by
diverse bacterial communities, residing in various environmental niches. This
study aims to understand the potential of a biosurfactant producing Bacillus sp.
AM13, isolated from soil. An integrated approach of genomic and chemical analysis
was employed to characterize the antibacterial lipopeptide produced by the strain
AM13. Genome analysis revealed that strain AM13 harbors a nonribosomal peptide
synthetase (NRPS) cluster; highly similar with known biosynthetic gene clusters
from surfactin family: lichenysin (85 %) and surfactin (78 %). These findings
were substantiated with supplementary experiments of oil displacement assay and
surface tension measurements, confirming the biosurfactant production. Further
investigation using LCMS approach exhibited similarity of the biomolecule with
biosurfactants of the surfactin family. Our consolidated effort of functional
genomics provided chemical as well as genetic leads for understanding the
biochemical characteristics of the bioactive compound.
PMID- 27492418
TI - Effects of constrained trunk movement on frontal plane gait kinematics.
AB - Previously it has been shown that constraining step width in gait coincides with
decreased trunk displacements. Conversely, external stabilization of the upper
body in gait coincides with decreased step width, but this may in part be due to
changes in passive dynamics of the leg. In the present study, trunk kinematics
during gait were constrained without external stabilization by using an orthosis,
to investigate whether step width and dynamic gait stability in the ML direction
are changed in relation to trunk kinematics. Nine healthy young adults walked on
a treadmill at three different speeds with no intervention and while wearing a
thoracolumbar orthosis. Based on marker trajectories, trunk COM displacement,
body COM displacement and velocity, step width, and margin-of-stability in ML
direction were calculated. The results showed that the orthosis significantly
reduced trunk and body COM displacements. As hypothesized, the restriction of
trunk movement coincided with significantly decreased step width, while the
margin-of-stability was not affected. These findings indicate that, when trunk
movements are constrained, humans narrow step width, while maintaining a constant
margin-of-stability. In conclusion, the present results in combination with
previous work imply that in gait a reciprocal coupling between trunk kinematics
and foot placement in the frontal plane subserves control of stability in the
frontal plane.
PMID- 27492420
TI - The bladder cancer drug market.
PMID- 27492419
TI - The Cost-Effectiveness of Oral Nutrition Supplementation for Malnourished Older
Hospital Patients.
AB - BACKGROUND: Malnutrition, which is associated with increased medical
complications in older hospitalized patients, can be attenuated by providing
nutritional supplements. OBJECTIVE: This study evaluates the cost effectiveness
of a specialized oral nutritional supplement (ONS) in malnourished older
hospitalized patients. METHODS: We conducted an economic evaluation alongside a
multicenter, randomized, controlled clinical trial (NOURISH Study). The target
population was malnourished older hospitalized patients in the USA. We used 90
day (base case) and lifetime (sensitivity analysis) time horizons. The study
compared a nutrient-dense ONS, containing high protein and beta-hydroxy-beta
methylbutyrate to placebo. Outcomes included health-care costs, measured as the
product of resource use and per unit cost; quality-adjusted life-years (QALYs)
(90-day time horizon); life-years (LYs) saved (lifetime time horizon); and the
incremental cost-effectiveness ratio (ICER). All costs were inflated to 2015 US
dollars. RESULTS: In the base-case analysis, 90-day treatment group costs
averaged US$22,506 per person, compared to US$22,133 for the control group.
Treatment group patients gained 0.011 more QALYs than control group subjects,
reflecting the treatment group's significantly greater probability of survival
through 90 days' follow-up, as reported by the clinical trial. Hence, the 90-day
follow-up period ICER was US$33,818/QALY. Assuming a lifetime time horizon,
estimated treatment group life expectancy exceeded control group life expectancy
by 0.71 years. Hence, the lifetime ICER was US$524/LY. The follow-up period for
the trial was relatively short. Some of the patients were lost to follow-up, thus
reducing collection of health-care utilization data during the clinical trial.
CONCLUSION: Our findings suggest that the investigative ONS cost-effectively
extends the lives of malnourished hospitalized patients.
PMID- 27492421
TI - How Online Peer-to-Peer Conversation Shapes the Effects of a Message About
Healthy Sleep.
AB - Conversation about health messages and campaigns is common, and message-related
conversations are increasingly recognized as a consequential factor in shaping
message effects. The evidence base is limited, however, about the conditions
under which conversation may help or hinder health communication efforts. In this
study, college students (N = 301) first watched a short sleep video and were
randomly assigned to either talk with a partner in an online chat conversation or
proceed directly to a short survey. Unknown to participants, the chat partner was
a confederate coached to say positive things about sleep and the message
('positive' chat condition), negative things ('negative' chat condition), or
unrelated things ('natural' chat condition). All respondents completed a short
survey on beliefs about sleep, reactions to the message, and intentions to get
adequate sleep. Respondents had greater intentions to engage in healthy sleep
when they engaged in positive conversation following message exposure than when
they engaged in negative conversation after the message (p < 0.001). Positive
emotion experienced in response to the message and positive chat perceptions were
significant predictors (p < 0.05) of intentions to achieve healthy sleep. Health
message designers may benefit from understanding how messages are exchanged in
peer-to-peer conversation to better predict and explain their effects.
PMID- 27492423
TI - International Cancer Education Conference 2016 Program and Abstracts.
PMID- 27492422
TI - Human eccrine sweat gland cells reconstitute polarized spheroids when
subcutaneously implanted with Matrigel in nude mice.
AB - Increasing evidence indicates that maintenance of cell polarity plays a pivotal
role in the regulation of glandular homeostasis and function. We examine the
markers for polarity at different time points to investigate the formation of
cell polarity during 3D reconstitution of eccrine sweat glands. Mixtures of
eccrine sweat gland cells and Matrigel were injected subcutaneously into the
inguinal regions of nude mice. At 2, 3, 4, 5 and 6 weeks post-implantation,
Matrigel plugs were removed and immunostained for basal collagen IV, lateral beta
catenin, lateroapical ZO-1 and apical F-actin. The results showed that the cell
polarity of the spheroids appeared in sequence. Formation of basal polarity was
prior to lateral, apical and lateroapical polarity. Collagen IV was detected
basally at 2 weeks, beta-catenin laterally and ZO-1 lateroapically at 3 weeks,
and F-actin apically at 4 weeks post-implantation. At week 5 and week 6, the
localization and the positive percentage of collagen IV, beta-catenin, ZO-1 or F
actin in spheroids was similar to that in native eccrine sweat glands. We
conclude that the reconstituted 3D eccrine sweat glands are functional or
potentially functional.
PMID- 27492424
TI - Qualitative Exploration of Sexual Health Among Diverse Breast Cancer Survivors.
AB - Although the physical and emotional impact of surgical removal of partial or
complete removal of the breast as well as effects of breast cancer treatment on
the individual have been well documented, little research is available on
sexuality and sexual health of breast cancer survivors in a relationship context.
Sexual health concerns of breast cancer survivors remain an unmet need for many.
The present study consisted of qualitative interviews with 135 racially diverse,
female breast cancer survivors who completed treatment to better understand their
perspectives on sexual health and management of sexual problems in their
potential and existing relationships after breast cancer. Key thematic findings
include that breast cancer survivors have to (1) adapt to the physical and
emotional traumas of breast cancer surgery and treatment, (2) navigate
complicated sexual communications with potential and existing partners, and (3)
negotiate intimacy and closeness without sexual intercourse with existing
partners. This study demonstrates the need for healthcare providers to discuss
sexual health after breast cancer with all of their patients as it is a concern
that faces single and partnered breast cancer survivors months and years after
treatment.
PMID- 27492425
TI - How well Informed are Cancer Patients Prior to a Life Cycle of Injectable
Chemotherapy Drug Treatment?
AB - Cancer patient dissatisfaction, due to a long waiting time for chemotherapy
treatment, is a common complaint. To improve patient satisfaction, our
pharmaceutical team was prompted to design a series of information tools for
injectable chemotherapy drug treatment (ICDT) patients. This study was based on
French Health Authorities recommendations. All three stages were monitored: the
preparation stage using a 204 patient survey, the design stage, and the
assessment stage with a 12 point questionnaire patient evaluation. An information
brochure and a 10-min film were designed which chronologically described key
stages in the life cycle of ICDT. Both tools were assessed by 29 and 84 patients
respectively. The questionnaire confirmed that this approach met the needs of
more than 90 % of patients. The brochure and the film also accurately met the
objectives and improved the understanding of the chemotherapy long waiting time
which resulted in higher patient satisfaction. The designed tools will continue
to evolve with changes in oncology practices based on various indicators defined
in the study. Our study proposes an original method to assist health
professionals to better inform cancer patients regarding the preparation of ICDT.
It is also a part of a continuous quality program to assure quality outpatient
healthcare.
PMID- 27492426
TI - Update on the Management of Pancreatic Cancer in Older Adults.
AB - Pancreatic cancer is more common in older adults, who are underrepresented in
clinical trials and frequently under treated. Chronological age alone should not
deter clinicians from offering treatment to geriatric patients, as they are a
heterogeneous population. Geriatric assessment, frailty assessment tools, and
toxicity risk scores help clinicians select appropriate patients for therapy. For
resectable disease, surgery can be safe but should be done at a high-volume
center. Adjuvant therapy is important; though there remains controversy on the
role of radiation, chemotherapy is well studied and efficacious. In locally
advanced unresectable disease, chemoradiation or chemotherapy alone is an option.
Neoadjuvant therapy improves the chances of resectability in borderline
resectable disease. Chemotherapy extends survival in metastatic disease, but
treatment goals and risk-benefit ratios have to be clarified. Adequate symptom
management and supportive care are important. There are now many new treatment
strategies and novel therapies for this disease.
PMID- 27492427
TI - Detection of spine structures with Bioimpedance Probe (BIP) Needle in clinical
lumbar punctures.
AB - Lumbar puncture is a relatively safe procedure, but some serious, even fatal,
complications can occur. Needle guidance can increase puncture accuracy, decrease
the number of attempts, and make the procedure easier. We tested the feasibility
of a bioimpedance-based tissue-sensing technology for needle guidance in clinical
use. The Bioimpedance Probe (BIP) Needle has a removable BIP stylet enabling
measurement of bioimpedance spectra during the procedure. The BIP Needle is
connected to a measurement device that uses tissue-classification software, and
the device provides audiovisual feedback when it detects cerebrospinal fluid
(CSF). We performed spinal anesthesia with the BIP Needle in 45 patients. The
device performance and needle tip location were verified by an experienced
anesthesiologist confirming CSF leakage. The device detected CSF in all cases
(sensitivity of 100 %). Six cases with false detections lowered the specificity
to 81 %, but in practice, most of these were easy to differentiate from true
detections because their duration was short and they occurred during backward
movement of the needle. The epidural spectrum differentiated as fatty tissue from
surrounding tissues, but the ligamentum flavum was not clearly detectable in the
data. The BIP Needle is a reliable tool for detecting CSF in lumbar puncture. It
can make the puncture procedure smoother, as repeated CSF flow tests are avoided.
The correct needle tip location is immediately detected, thus unnecessary needle
movements close to spinal nerves are prevented. Physicians could benefit from the
information provided by the BIP Needle, especially in patients with obesity or
anatomic alterations.
PMID- 27492428
TI - Observation of ventilation effects of I-gelTM, SupremeTM and Ambu AuraOnceTM with
respiratory dynamics monitoring in small children.
AB - The shortcomings of laryngeal mask airway (LMATM), such as upper airway
obstruction and gastric distension or airway leakage, may limit its application
in small children. The I-gelTM (I-gel), LMA-SupremeTM (LMA-S), and Ambu
AuraOnceTM (Ambu) are three improvements upon these shortcomings. This study
adopted respiratory dynamic monitoring to observe the ventilation parameters of
the three laryngeal masks in small children. A total of 105 children were
randomized into Ambu (n = 35), I-gel (n = 35), and LMA-S (n = 35) groups. Primary
outcomes included leak pressure and respiratory dynamic data. Secondary outcomes
included hemodynamic data and bispectral index values after induction (T0), time
after successful laryngeal mask insertion (T1) and at three recording points
every 10 min after insertion (T2, T3, and T4), as well as laryngeal mask related
adverse reactions. The inspiratory/expiratory tidal volume per kilogram of body
weight in the Ambu group was significantly different from those in the other
groups (P < 0.05), while the leak pressure in the Ambu group was significantly
lower (P < 0.05). At T3 and T4, the expiratory resistance values in the Ambu
group were significantly lower than those in the LMA-S group (P < 0.05). We have
shown that the three laryngeal masks provided secure ventilation in children <6
years of age by using continuous respiratory dynamic monitoring. We concluded
that the I-gel presented a better sealing effect and fewer adverse reactions.
PMID- 27492429
TI - Effective evaluation of arterial pulse waveform analysis by two-dimensional
stroke volume variation-stroke volume index plots.
AB - Arterial pulse waveform analysis (APWA) with a semi-invasive cardiac output
monitoring device is popular in perioperative hemodynamic and fluid management.
However, in APWA, evaluation of hemodynamic data is not well discussed. In this
study, we analyzed how we visually interpret hemodynamic data, including stroke
volume variation (SVV) and stroke volume (SV) derived from APWA. We performed
arithmetic estimation of the SVV-SV relationship and applied measured values to
this estimation. We then collected measured values in six anesthesia cases,
including three liver transplantations and three other types of surgeries, to
apply them to this SVV-SVI (stroke volume variation index) plot. Arithmetic
analysis showed that the relationship between SVV and SV can be drawn as
hyperbolic curves. Plotting SVV-SV values in the semi-logarithmic scale showed
linear correlations, and the slopes of the linear regression lines theoretically
represented average mean cardiac contractility. In clinical measurements in APWA,
plotting SVV and SVI values in the linear scale and the semi-logarithmic scale
showed the correlations represented by hyperbolic curves and linear regression
lines. The plots approximately shifted on the rectangular hyperbolic curves,
depending on blood loss and blood transfusion. Arithmetic estimation is close to
real measurement of the SVV-SV interaction in hyperbolic curves. In APWA, using
SVV as an index of preload and the cardiac index or SVI derived from arterial
pressure-based cardiac output as an index of cardiac function, is likely to be
appropriate for categorizing hemodynamic stages as a substitute for Forrester
subsets.
PMID- 27492430
TI - Safety analysis of laparoscopic endoscopic cooperative surgery versus endoscopic
submucosal dissection for selected gastric gastrointestinal stromal tumors: a
propensity score-matched study.
AB - BACKGROUND: Laparoscopic endoscopic cooperative surgery (LECS) is a safe
alternative to endoscopic submucosal dissection (ESD) for select gastric
gastrointestinal stromal tumors (GISTs) that are <2 cm in size. To date, there
have been no randomized studies comparing the feasibility of these two
techniques. Therefore, we compared their feasibility and safety using the
propensity score matching method in this study. METHODS: This was a single
center, retrospective, propensity score-matched study of patients who underwent
resection of selected gastric GISTs between 2004 and 2014. All patients underwent
curative resection for pathologically diagnosed small gastric GISTs. The primary
aim was to determine intraoperative complications and postoperative courses. To
overcome selection biases, we performed a 1:1 match using five covariates,
including age, gender, body mass index, Charlson comorbidity index, and tumor
location, to generate propensity scores. RESULTS: In total, 32 patients treated
with LECS and 102 patients treated with ESD were balanced into 30 pairs. The rate
of intraoperative complications was significantly lower in the LECS group than in
the ESD group (P = 0.029). LECS patients had less intraoperative bleeding than
did ESD patients (15.0 ml [range 9.5-50.0 ml] vs. 43.5 ml [range 22.3-56.0 ml], P
= 0.004). The two groups had similar postoperative courses. There was no
difference in the reoperation rate between the two groups (P = 0.112). The ESD
group had a shorter operating time than did the LECS group (41.5 min vs. 96.5
min, P < 0.001). However, during a follow-up of 57.9 (+/-28.9) months, the
recurrence rate did not differ significantly between the two groups (0.0 vs. 6.7
%, respectively; P = 0.256). CONCLUSIONS: LECS for selected gastric GIST patients
is feasible and is associated with a better intraoperative outcome and an equal
postoperative course compared with the results of ESD.
PMID- 27492431
TI - A new method (the "Pincers maneuver") for lymphadenectomy along the right
recurrent laryngeal nerve during thoracoscopic esophagectomy in the prone
position for esophageal cancer.
AB - BACKGROUND: In esophageal squamous cell carcinoma, the number of dissected lymph
nodes (LNs), including those along the recurrent laryngeal nerves (RLNs),
influences prognosis and nodal staging accuracy. However, dissection of LNs along
the RLN increases the risk of complications, especially RLN palsy. Therefore,
complete dissection of these LNs with prevention of RLN palsy is recommended. We
present herein a new method for lymphadenectomy along the right RLN, named the
Pincers maneuver, during thoracoscopic esophagectomy in the prone position (TEP).
METHODS: The fundamental concept in this new method is to first exfoliate the two
dimensional membrane (lateral pedicle), which includes the right RLN, LNs along
the right RLN, and the primary esophageal artery, from the right side of the
trachea toward the neck. Using a Pincers strategy, closing in from the inner and
outer sides of the two-dimensional membrane (lateral pedicle), lymphadenectomy
along the right RLN toward the right inferior thyroid artery should be easy. This
technique was evaluated in 30 consecutive cases of TEP for squamous cell cancer.
RESULTS: There were 15 patients who underwent the new method (Pincers maneuver;
Pm) and 15 patients who underwent the conventional method (Cm). There were no
significant differences between the two groups in the duration of the thoracic
procedure and dissection along the right RLN. No intraoperative and postoperative
morbidity related to the right RLN was observed in either group. The Pm group had
a higher number of dissected LNs along the right RLN than the Cm group (6.3 vs
3.1, p = 0.044). CONCLUSIONS: The Pincers maneuver for lymphadenectomy along the
right RLN during TEP is technically safe and feasible. It increases the number of
dissected LNs along the right RLN.
PMID- 27492432
TI - Bilateral areolar endoscopic Sistrunk operation: a novel technique for
thyroglossal duct cyst surgery.
AB - BACKGROUND: Sistrunk operation of the thyroglossal duct is a procedure for the
removal of a cyst, the middle part of the hyoid bone and tract towards the
foramen caecum. Unavoidably, this procedure results in a scar on the skin in the
neck area. By performing a bilateral areolar endoscopic Sistrunk operation, this
study is the first to develop a procedure that can solve the aesthetic problem.
This operation results in both an excellent cosmetic result and the successful
treatment of TGDC. METHODS: A three-port technique was performed in this
operation: 10-mm port for 30 degrees , 10-mm laparoscope, 5-mm port for the
instrument at the left circumareolar area and 5-mm port located at the right
circumareolar area. Insufflation pressure of CO2 gas was set at 6 mm Hg. The
surgical working space was located over the breast tissue and pectoralis muscles,
towards the anterior neck to the hyoid bone. The steps employed for resection
were similar to a conventional Sistrunk operation using standard laparoscopic
instruments and hook scissors. RESULTS: A series of 11 patients were successfully
treated using this novel technique with neither conversion to open surgery nor
surgical complications. Average operative time was 88.54 min (ranging from 60 to
130 min). Average blood loss was 35 mL. (ranging from 15 to 67 mL). Patients were
discharged in an average of 2.36 days after the procedure (ranging from 2 to 3
days). CONCLUSION: This novel technique for TGDC Sistrunk surgery using an
areolar approach is feasible, safe and effective. The benefit of this technique
is the cosmetic result, which leaves no scarring on the neck after wound healing
and may provide a new method for optimal aesthetic results.
PMID- 27492433
TI - ?
PMID- 27492434
TI - [Pyoderma gangrenosum].
AB - Pyoderma gangrenosum (PG) is an ulcerating, neutrophilic dermatosis of unknown
etiology. Clinical appearance is characterized by sudden onset of sterile
pustules that rapidly develop into very painful ulcerations with violaceous,
undermined borders. Due to the lack of specific diagnostic and therapeutic
markers, PG is a diagnosis of exclusion. An association with further diseases
such as chronic inflammatory bowel disease, rheumatoid arthritis, diabetes,
neoplasms, or metabolic syndrome exists in over 50 % of cases. Treatment of PG
consists of suppression of inflammatory disease activity, treatment of associated
morbidities, promotion of wound healing, and pain relief. Recommended first-line
treatment consists of systemic glucocorticosteroids and additional or
alternatively cyclosporine. A controlled trial on infliximab in PG points to
efficacy of TNF-alpha antagonists. Due to chronicity, frequent recurrences, and
often complicated courses, treatment with good tolerability is important.
PMID- 27492435
TI - Prediction of hip osteoporosis by DXA using a novel pulse-echo ultrasound device.
AB - : Pulse-echo ultrasonometry can be used as a pre-screen for hip osteoporosis
before dual-energy x-ray absorptiometry (DXA), potentially allowing DXA to be
avoided for the majority of post-menopausal women. Pulse-echo ultrasound measures
of tibia cortical thickness are also associated with radiographically confirmed
prior fractures, independent of femoral neck bone mineral density. INTRODUCTION:
To estimate how well a pulse-echo ultrasound device discriminates those who have
from those who do not have hip osteoporosis (femoral neck bone mineral density
[BMD] or total hip BMD T-score <= -2.5), and to estimate the association of pulse
echo ultrasound measures with prevalent (radiographically confirmed) clinical
fractures. METHODS: Five hundred fifty-five post-menopausal women age 50 to 89
had femoral neck and total hip BMD measured by dual-energy x-ray absorptiometry
(DXA), and pulse-echo ultrasound measures of distal radius, proximal tibia,
distal tibia cortical thickness, and multi- and single-site density indices (DI).
Using previously published threshold ultrasound values, we estimated the
proportion of women who would avoid a follow-up DXA after pulse-echo
ultrasonometry, and the sensitivity and specificity of this for the detection of
hip osteoporosis. Logistic regression models were used to estimate the
associations of pulse-echo ultrasound measures with radiographically confirmed
clinical fractures within the prior 5 years. RESULTS: Using multi-site and single
site DI measures, follow-up DXA could be avoided for 73 and 69 % of individuals,
respectively, while detecting hip osteoporosis with 80-82 % sensitivity and 81 %
specificity. Radiographically confirmed prior fracture was associated with
ultrasound measures of single-site DI (odds ratio (OR) 1.55, 95 % confidence
interval (CI). 1.06 to 2.26) and proximal tibia cortical thickness (OR 1.47, 95 %
CI 1.10 to 1.96), adjusted for age, body mass index, and femoral neck BMD.
CONCLUSIONS: Pulse-echo ultrasonometry can be used as an initial screening test
for hip osteoporosis. Prospective studies of how well pulse-echo ultrasound
measures predict subsequent clinical fractures are warranted.
PMID- 27492436
TI - Osteogenesis imperfecta in children and adolescents-new developments in diagnosis
and treatment.
AB - Osteogenesis imperfecta (OI) is the most prevalent heritable bone fragility
disorder in children. It has been known for three decades that the majority of
individuals with OI have mutations in COL1A1 or COL1A2, the two genes coding for
collagen type I alpha chains, but in the past 10 years defects in at least 17
other genes have been linked to OI. Almost all individuals with a typical OI
phenotype have a mutation in one of the currently known genes. Regarding medical
treatment, intravenous bisphosphonate therapy is the most widely used medical
approach. This has a marked effect on vertebra in growing children and can lead
to vertebral reshaping after compression fractures, but there is little effect of
bisphosphonate therapy on the development of scoliosis. Bisphosphonate treatment
decreases long-bone fracture rates, but such fractures are still frequent. Newer
medications with anti-resorptive and bone anabolic action are being investigated
in an attempt to improve on the efficacy of bisphosphonates but the safety and
efficacy of these new approaches in children with OI is not yet established.
PMID- 27492437
TI - Association between education and future leisure-time physical inactivity: a
study of Finnish twins over a 35-year follow-up.
AB - BACKGROUND: Education is associated with health related lifestyle choices
including leisure-time physical inactivity. However, the longitudinal
associations between education and inactivity merit further studies. We
investigated the association between education and leisure-time physical
inactivity over a 35-year follow-up with four time points controlling for
multiple covariates including familial confounding. METHODS: This study of the
population-based Finnish Twin Cohort consisted of 5254 twin individuals born in
1945-1957 (59 % women), of which 1604 were complete same-sexed twin pairs. Data
on leisure-time physical activity and multiple covariates was available from four
surveys conducted in 1975, 1981, 1990 and 2011 (response rates 72 to 89 %). The
association between years of education and leisure-time physical inactivity (<1.5
metabolic equivalent hours/day) was first analysed for each survey. Then, the
role of education was investigated for 15-year and 35-year inactivity periods in
the longitudinal analyses. The co-twin control design was used to analyse the
potential familial confounding of the effects. All analyses were conducted with
and without multiple covariates. Odds Ratios (OR) with 95 % Confidence Intervals
(CI) were calculated using logistic and conditional (fixed-effects) regression
models. RESULTS: Each additional year of education was associated with less
inactivity (OR 0.94 to 0.95, 95 % CI 0.92, 0.99) in the cross-sectional age- and
sex-adjusted analyses. The associations of education with inactivity in the 15-
and 35-year follow-ups showed a similar trend: OR 0.97 (95 % CI 0.93, 1.00) and
OR 0.94 (95 % CI 0.91, 0.98), respectively. In all co-twin control analyses, each
year of higher education was associated with a reduced likelihood of inactivity
suggesting direct effect (i.e. independent from familial confounding) of
education on inactivity. However, the point estimates were lower than in the
individual-level analyses. Adjustment for multiple covariates did not change
these associations. CONCLUSIONS: Higher education is associated with lower odds
of leisure-time physical inactivity during the three-decade follow-up. The
association was found after adjusting for several confounders, including familial
factors. Hence, the results point to the conclusion that education has an
independent role in the development of long-term physical inactivity and tailored
efforts to promote physical activity among lower educated people would be needed
throughout adulthood.
PMID- 27492438
TI - Validation and comparison of instruments to identify frail patientes in primary
care settings: Study protocol.
AB - BACKGROUND: In the last few years several indices and tools, aimed at identifying
frail subjects in various care settings have been developed. However, to date
none of them has been incorporated into usual practice in the primary care
setting. The purposes of this study are: 1) to evaluate the predictive capacity
of the Tilburg Frailty Indicator (TFI), the Gerontopole Frailty Screening Tool
(GFST) and the KoS model together with two biomarker levels (SOX2 and p16INK4a)
for adverse events related to frailty; 2) to determine differences in the use of
healthcare services according to frailty. METHODS/DESIGN: Prospective multicentre
cohort study with a 2-year follow-up. The study will be performed in primary care
centres of Gipuzkoa and Costa del Sol, both located in Spain. Autonomous, non
institutionalized individuals aged 70 and over that agree to participate in this
study will constitute the study population. A total of 900 individuals will be
randomly selected from the healthcare administrative data bases of the
participating health services. Data will be collected at baseline and at 1 and 2
years. The main independent variables assessed at baseline will be TFI outcomes,
GFST and the KoS model, together with the expression of SOX2 and p16INK4a levels.
During follow-up, loss of autonomy, the occurrence of death and consumption of
healthcare resources will be assessed. DISCUSSION: The main focus of this work is
the identification and evaluation of several instruments constructed under
different rationales to identify frail subjects in primary care settings. The
resulting outcomes have potential for direct application to the primary care
practice. Early identification of the onset of functional impairment of elderly
is an essential, still unresolved aspect in the prevention of dependence in the
scope of primary care.
PMID- 27492439
TI - Optimizing Silicon Oxide Embedded Silicon Nanocrystal Inter-particle Distances.
AB - We demonstrate an analytical method to optimize the stoichiometry and thickness
of multilayer silicon oxide films in order to achieve the highest density of non
touching and closely spaced silicon nanocrystals after annealing. The probability
of a nanocrystal nearest-neighbor distance within a limited range is calculated
using the stoichiometry of the as-deposited film and the crystallinity of the
annealed film as input parameters. Multiplying this probability with the
nanocrystal density results in the density of non-touching and closely spaced
silicon nanocrystals. This method can be used to estimate the best as-deposited
stoichiometry in order to achieve optimal nanocrystal density and spacing after a
subsequent annealing step.
PMID- 27492441
TI - Erratum to: Novel nitrifiers and comammox in a full-scale hybrid biofilm and
activated sludge reactor revealed by metagenomic approach.
PMID- 27492440
TI - Classifying publications from the clinical and translational science award
program along the translational research spectrum: a machine learning approach.
AB - BACKGROUND: Translational research is a key area of focus of the National
Institutes of Health (NIH), as demonstrated by the substantial investment in the
Clinical and Translational Science Award (CTSA) program. The goal of the CTSA
program is to accelerate the translation of discoveries from the bench to the
bedside and into communities. Different classification systems have been used to
capture the spectrum of basic to clinical to population health research, with
substantial differences in the number of categories and their definitions.
Evaluation of the effectiveness of the CTSA program and of translational research
in general is hampered by the lack of rigor in these definitions and their
application. This study adds rigor to the classification process by creating a
checklist to evaluate publications across the translational spectrum and
operationalizes these classifications by building machine learning-based text
classifiers to categorize these publications. METHODS: Based on collaboratively
developed definitions, we created a detailed checklist for categories along the
translational spectrum from T0 to T4. We applied the checklist to CTSA-linked
publications to construct a set of coded publications for use in training machine
learning-based text classifiers to classify publications within these categories.
The training sets combined T1/T2 and T3/T4 categories due to low frequency of
these publication types compared to the frequency of T0 publications. We then
compared classifier performance across different algorithms and feature sets and
applied the classifiers to all publications in PubMed indexed to CTSA grants. To
validate the algorithm, we manually classified the articles with the top 100
scores from each classifier. RESULTS: The definitions and checklist facilitated
classification and resulted in good inter-rater reliability for coding
publications for the training set. Very good performance was achieved for the
classifiers as represented by the area under the receiver operating curves (AUC),
with an AUC of 0.94 for the T0 classifier, 0.84 for T1/T2, and 0.92 for T3/T4.
CONCLUSIONS: The combination of definitions agreed upon by five CTSA hubs, a
checklist that facilitates more uniform definition interpretation, and algorithms
that perform well in classifying publications along the translational spectrum
provide a basis for establishing and applying uniform definitions of
translational research categories. The classification algorithms allow
publication analyses that would not be feasible with manual classification, such
as assessing the distribution and trends of publications across the CTSA network
and comparing the categories of publications and their citations to assess
knowledge transfer across the translational research spectrum.
PMID- 27492442
TI - Mx oligomer: a novel capsid pattern sensor?
AB - Myxovirus resistance proteins represent a family of interferon-induced
restriction factors of the innate and adaptive immune system. Human MxB acts as a
novel restriction factor with antiviral activity against a range of HIV-1 and
other retroviruses mainly by inhibiting the uncoating process after reverse
transcription but prior to integration. Based on published data and conservation
analysis, we propose a novel hypothesis, in which MxB dimers form higher order
oligomers that restrict retroviral replication by binding to the viral capsid.
Insights into the mechanistic basis of structural and functional characteristics
of MxB will greatly advance our understanding of MxB.
PMID- 27492444
TI - Resistive switching of alkanethiolated nanoparticle monolayers patterned by
electron-beam exposure.
AB - Carbon-based electronic devices are promising candidates for complementing
silicon-based electronics in memory device applications. For example, sputtered
thin films of amorphous carbon exhibit memristive behavior. The reported devices,
however, have a minimal active area of about 50 nm diameter, leading to large set
currents in the MUA range. Although power efficiency would benefit from reduced
drive currents, resistive switching of amorphous carbon confined to a few cubic
nanometers has remained largely unexplored. Here, we investigate resistive
switching in 30 nm long and 25 nm wide monolayer arrays of 10 nm gold
nanoparticles patterned by direct electron-beam exposure followed by a purpose
designed emulsion-based development process. Electron-beam irradiation transforms
the alkanethiol ligands of the gold nanoparticles into a solvent-resistant
amorphous carbonaceous matrix allowing pattern development and imparting
electronic function. We measure changes in conductivity of up to five orders of
magnitude for set currents in the nA range.
PMID- 27492443
TI - Age and time trends in eating frequency and duration of nightly fasting of German
children and adolescents.
AB - PURPOSE: To describe age and time trends in eating occasion frequency (EOF), meal
frequency (MF), snack frequency (SF) and duration of nightly fasting (DNF) in
German children and adolescents. METHODS: 9757 3-day dietary records of 1246 3-18
year-old participants of the open DONALD cohort study, collected 1985-2014, were
analyzed for age and time trends using polynomial mixed-effects regression
models. Eating occasions were either assigned to meals or snacks (>10 or <=10 %
of daily total energy intake per eating occasion). DNF was defined as the longest
time span without energy intake within one night. RESULTS: EOF, MF and SF
decreased with age (EOF: linear, quadratic, cubic trend p < 0.0001; MF: linear
trend p < 0.0001; SF: linear, quadratic trend p < 0.0001). Time trend analyses
revealed a wavelike time course for EOF (linear trend p = 0.0580, quadratic trend
= 0.0039, cubic trend = 0.0015) and SF (linear trend p = 0.0055, quadratic trend
p = 0.0005, cubic trend p = 0.0003). MF slightly increased until 2000 and
decreased thereafter (linear trend p = 0.0012, quadratic trend p = 0.0047).
Effect sizes of time trends in EOF, MF and SF were small. Boys' and girls' DNF
decreased with age (in both: linear, quadratic, cubic trend p < 0.0001) and
increased over the study period (boys: linear trend p = 0.0011, interaction of
age and time p < 0.0001; girls: linear trend p = 0.0167). CONCLUSION: EOF, MF and
SF were higher in children than in adolescents, but, in contrast to other studies
remained fairly stable over the study period. Decreasing DNF with age could
reflect decreasing sleep durations. Additionally, DNF increased over the study
period, probably due to an increase in breakfast skipping.
PMID- 27492445
TI - Nonkeratinizing Squamous Cell Carcinoma In Situ of the Upper Aerodigestive Tract:
An HPV-Related Entity.
AB - The clinical and pathologic characteristics of human papillomavirus (HPV)-related
premalignant lesions in the upper aerodigestive tract have not been adequately
studied. There are a few reports of oral cavity HPV-related severe dysplasia with
unique morphology (prominent apoptosis/karyorrhexis imparting a 'bowenoid'
appearance) and a single case report of HPV-related squamous cell carcinoma in
situ with nonkeratinizing histology distinct from the 'bowenoid' pattern that
extensively involved the upper aerodigestive tract. The aim of this study was to
characterize the morphologic and clinical features of HPV-related severe
dysplasia/carcinoma in situ. All cases of upper aerodigestive tract severe
dysplasia/carcinoma in situ (111 cases from 98 patients) at Washington University
from July 2012 to March 2015 were categorized into histologic types:
keratinizing, nonkeratinizing, mixed or 'bowenoid'. There were 83 (85 %) patients
with keratinizing, 3 (3 %) nonkeratinizing and 12 (12 %) mixed patterns. The
previously reported 'bowenoid' morphology was not identified. All 3 (100 %)
nonkeratinizing and 6 (50 %) mixed cases were p16 and HPV RNA in situ
hybridization (RNA ISH) positive (100 % concordance between p16 and RNA ISH).
Only 2 of 73 keratinizing cases were p16 positive, 1 of which was also HPV RNA
ISH positive (1.4 % of keratinizing cases HPV-related). Thus, nonkeratinizing
morphology was a strong predictor of transcriptionally-active HPV in severe
dysplasia/carcinoma in situ. HPV-related cases most commonly occurred in the
floor of mouth and were frequently extensive (>=4 cm) or unresectable.
PMID- 27492446
TI - Well-Differentiated Laryngeal/Hypopharyngeal Liposarcoma in the MDM2 Era Report
of Three Cases and Literature Review.
AB - Laryngeal/hypopharyngeal liposarcomas are very rare, fewer than 40 cases have
been reported. These tumors are polypoid, with a male predisposition, and usually
cause hoarseness and difficulty breathing. Their clinical course is characterized
by multiple local recurrences. No distant metastasis has been reported, and
dedifferentiation is extremely rare. In sum, the prognosis of these tumors is
excellent; the 5-year survival rate is essentially 100 %. Pathologic diagnosis of
these well-differentiated liposarcomas can be challenging. Many of them were
initially diagnosed as benign lipoma, fibrovascular polyp, or "inflammatory
polyp". The correct diagnosis is usually made after multiple recurrences. On the
other hand, the literature bears out that these incorrect diagnoses do not impact
disease-specific survival. Here, we report three patients with
laryngeal/hypopharyngeal well-differentiated liposarcomas; this is the first
documentation of MDM2 amplification in liposarcomas at this site.
PMID- 27492448
TI - Caffeine discontinuation improves acute migraine treatment: a prospective clinic
based study.
AB - BACKGROUND: Caffeine has both excitatory and vasoconstrictive effects on central
nervous system. Caffeine use might be associated with development and
chronification of migraine. We aimed to evaluate the effect of caffeine cessation
on the acute treatment of migraine. METHODS: We prospectively recruited migraine
patients who consumed caffeine drinks daily and instructed them to discontinue
their caffeine intake. Triptans were prescribed for acute treatment. Patients
were followed up after at least two weeks after screening and evaluated the
efficacy of acute treatment with the migraine assessment of current therapy
(Migraine-ACT) questionnaire. Excellent efficacy was defined as Migraine-ACT
score of 4. Chronic migraine, body mass index, allodynia, depression, anxiety,
antiemetic use, and use of prophylactic medication were included in the
multivariate analysis if the univariate p < 0.2. FINDINGS: Among 108 patients
included, 36 completely discontinued their caffeine intake (abstinence group).
The efficacy of acute treatment was assessed at median 34.5 days (interquartile
range, 28-89) after the screening. Twenty-six patients (72.2 %) in the abstinence
group and 29 (40.3 %) in the non-abstinence group reported an excellent efficacy
(p = 0.002). The abstinence group also showed a trend toward greater reduction of
headache impact test-6 (HIT-6) scores (p = 0.085). Caffeine abstinence was
independently associated with an excellent efficacy of acute treatment
(multivariate odds ratio, 3.2; 95 % confidence interval, 1.2-8.4; p = 0.018)
after controlling for covariates. CONCLUSIONS: Caffeine abstinence is associated
with better efficacy of acute migraine treatment. Our uncontrolled study results
encourage a further confirmatory study on this issue.
PMID- 27492449
TI - A profile of four patterns of vulnerability to functional decline in older
general medicine patients in Victoria, Australia: a cross sectional survey.
AB - BACKGROUND: There are limited published data reporting Australian hospitalized
elders' vulnerability to functional decline to guide best practice interventions.
The objectives of this study were to describe the prevalence of vulnerability to
functional decline and explore profiles of vulnerability related to the
performance of physical activity in a representative group of elders in a single
centre in Victoria, Australia. METHODS: A cross-sectional survey of patients aged
>= 70 years (Mean age 82.4, SD 7 years) admitted to a general medical ward of an
Australian tertiary-referral metropolitan public hospital from March 2010 to
March 2011 (n = 526). Patients were screened using the Vulnerable Elders Survey
(VES-13). Distinct typologies of physical difficulties were identified using
latent class analysis. RESULTS: Most elders scored >=3/10 on the VES-13 and were
rated vulnerable to functional decline (n = 480, 89.5 %). Four distinct classes
of physical difficulty were identified: 1) Elders with higher physical
functioning (n = 114, 21.7 %); 2) Ambulant elders with diminished strength (n =
24, 4.6 %); 3) Elders with impaired mobility, strength and ability to stoop (n =
267, 50.8 %) and 4) Elders with extensive physical impairment (n = 121, 23 %)
Vulnerable elders were distributed through all classes. CONCLUSIONS: Older
general medicine patients in Victoria, Australia, are highly vulnerable to
functional decline. We identified four distinct patterns of physical difficulties
associated with vulnerability to functional decline that can inform health
service planning, delivery and education.
PMID- 27492450
TI - Obesity in Older People With and Without Conditions Associated With Weight Loss:
Follow-up of 955,000 Primary Care Patients.
AB - BACKGROUND: Moderate obesity in later life may improve survival, prompting calls
to revise obesity control policies. However, this obesity paradox may be due to
confounding from smoking, diseases causing weight-loss, plus varying follow-up
periods. We aimed to estimate body mass index (BMI) associations with mortality,
incident type 2 diabetes, and coronary heart disease in older people with and
without the above confounders. METHODS: Cohort analysis in Clinical Practice
Research Datalink primary care, hospital and death certificate electronic medical
records in England for ages 60 to more than 85 years. Models were adjusted for
age, gender, alcohol use, smoking, calendar year, and socioeconomic status.
RESULTS: Overall, BMI 30-34.9 (obesity class 1) was associated with lower overall
death rates in all age groups. However, after excluding the specific confounders
and follow-up less than 4 years, BMI mortality risk curves at age 65-69 were U
shaped, with raised risks at lower BMIs, a nadir between 23 and 26.9 and steeply
rising risks above. In older age groups, mortality nadirs were at modestly higher
BMIs (all <30) and risk slopes at higher BMIs were less marked, becoming
nonsignificant at age 85 and older. Incidence of diabetes was raised for obesity
1 at all ages and for coronary heart disease to age 84. CONCLUSIONS: Obesity is
associated with shorter survival plus higher incidence of coronary heart disease
and type 2 diabetes in older populations after accounting for the studied
confounders, at least to age 84. These results cast doubt on calls to revise
obesity control policies based on the claimed risk paradox at older ages.
PMID- 27492451
TI - Comorbidity Indices Versus Function as Potential Predictors of 30-Day Readmission
in Older Patients Following Postacute Rehabilitation.
AB - BACKGROUND: Information regarding the association of comorbidity indices with
readmission risk for older adults receiving postacute care is limited. The
purpose of this study was to compare the discriminatory ability of five
comorbidity indices in predicting 30-day all-cause hospital readmission following
discharge to the community from postacute inpatient rehabilitation facilities
(IRF). METHODS: The sample included Medicare fee-for-service beneficiaries with
stroke, lower extremity joint replacement, and fracture, discharged from IRF in
2011 (N = 75,582). Logistic regression models were used to predict 30-day all
cause readmission. Impairment-specific base models included demographic
characteristics and length of stay. Subsequent models included individual
comorbidity indices: Tier, Charlson, Elixhauser, functional comorbidity index
(FCI), and the hierarchical condition category (HCC). We then added discharge
functional status to each model. Results were compared using C-statistics.
RESULTS: Thirty-day readmission rates following discharge from an IRF ranged from
6.5% (joint replacement) to 14% (stroke). The C-statistics were 0.53, 0.56, and
0.55 for the base models in the stroke, joint replacement, and fracture groups,
respectively. Adding the Tier, Charlson, FCI, or Elixhauser variables increased
the C-statistics by 0.03-0.07 across the three impairment categories. Adding the
HCC increased the C-statistics by 0.06-0.09. With the addition of discharge
functional status in the model, the C-statistics further increased by 0.06-0.09.
CONCLUSIONS: Comorbidity indices were weakly associated with 30-day readmission
in older adults discharged from postacute inpatient rehabilitation. Adding
patient-level functional status to the comorbidity indices further improved the
discriminatory ability to predict readmission in our sample.
PMID- 27492453
TI - Testing the role of glucose in self-control: A meta-analysis.
AB - The glucose view of self-control posited glucose as the physiological substrate
of self-control "resource", which results in three direct corollaries: 1)
engaging in a specific self-control activity would result in reduced glucose
level; 2) the remaining glucose level after initial exertion of self-control
would be positively correlated with following self-control performance; 3)
restoring glucose by ingestion would help to improve the impaired self-control
performance. The current research conducted a meta-analysis to test how well each
of the three corollaries of the glucose view would be empirically supported. We
also tested the restoring effect of glucose rinsing on subsequent self-control
performance after initial exertion. The results provided clear and consistent
evidence against the glucose view of self-control such that none of the three
corollaries was supported. In contrast, the effect of glucose rinsing turned out
to be significant, but with alarming signs of publication bias. The implications
and future directions are discussed.
PMID- 27492452
TI - Diosmin Modulates the NF-kB Signal Transduction Pathways and Downregulation of
Various Oxidative Stress Markers in Alloxan-Induced Diabetic Nephropathy.
AB - Hyperglycaemia-mediated oxidative stress plays an imperative role in the
progression of diabetic nephropathy. NF-kB is an important transcription factor
in eukaryotes which regulates a diverse array of cellular process, including
inflammation, immunological response, apoptosis, growth and development.
Increased expression of NF-kB plays a vital role in the pathogenesis of many
inflammatory diseases including diabetic nephropathy. Hence, the present study
was designed to explore the nephroprotective nature of diosmin by assessing the
various biochemical parameters, markers of oxidative stress and proinflammatory
cytokine levels in alloxan-induced diabetic Wistar rats. Type 2 diabetes was
induced in Wistar rats by single intraperitoneal injection of alloxan (120 mg/kg
body weight). Seventy-two hours after the conformation of diabetes (blood glucose
level >= 250 mg/dl), the rats were segregated into four groups, each group having
six animals. Diabetic rats were treated with diosmin at a dose of 50 mg and 100
mg/kg body weight respectively. After the 28th day of treatment, rats were
sacrificed, blood serum, plasma and kidney tissue were collected for various
biochemical analysis. Inflammatory cytokine levels were measured through ELISA
kit. Diosmin treatment produces significant reduction in the blood glucose and
plasma insulin level and increases the body weight when compared with diabetic
rats. Elevated level of malondialdehyde (MDA) and decrease levels of superoxide
dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and nitric oxide (NO)
were significantly restored after 28 days of diosmin treatment. Diosmin treatment
group also restores the normal architecture of the kidney tissue which was
confirmed by histopathological examination. Moreover, oral administration of
diosmin shows a significant normalization in the level of NF-kB, proving its
pivotal role in maintaining renal function. The above ameliorative effects were
more pronounced with diosmin at a dose of 100 mg/kg body weight. The above
results permit us to conclude that treatment with diosmin halts hyperglycaemia
mediated oxidative stress and decline in pro-inflammatory cytokines and thus has
beneficial anti-diabetic activity.
PMID- 27492454
TI - Predictors of health-related quality of life and association with survival may
identify colorectal cancer patients at high risk of poor prognosis.
AB - PURPOSE: To investigate the mediators of health-related quality of life (HR-QoL)
in colorectal cancer (CRC) patients and effect on overall survival. METHODS: We
analyzed baseline (within 1 year of diagnosis) SF-12v1 questionnaire data from
3734 CRC patients and assessed the differences in mental composite scores (MCS)
and physical composite scores (PCS) by socio-demographics and risks of poor HR
QoL by these factors. Hazard ratios were generated using univariate Cox
regression for MCS and PCS dichotomized using the normalized scoring-based mean
of 50 and survival estimates generated using the Kaplan-Meier method. RESULTS:
Differences in MCS and PCS were identified by sex, age, education level, alcohol
use, tobacco use, and stage. Race, marital status, and cancer site differed only
by PCS. Being female, never married, former alcohol user, or with stage IV
disease significantly increased risk of a poor HR-QoL, with magnitudes of risk
from 1.25- to 1.97-fold. Higher education level had a protective effect (MCS: P
trend = 2.32 * 10-7; PCS: P trend = 5.62 * 10-14). Hispanics and African
Americans had a 1.35- and 1.57-fold risk of poor PCS, and increase in age had a
protective effect for risk of poor MCS (P trend = 1.84 * 10-7). Poor MCS or PCS
were associated with poor prognosis and decreased survival at 5 years (HRMCS
1.57, 95 % CI 1.41-1.76 and HRPCS 2.38, 95 % CI 2.08-2.72), and both remained
significant when adjusting for age, gender, race, education level, tumor stage,
and tumor site. CONCLUSIONS: Our findings identify potential mediators for HR-QoL
and suggest that baseline HR-QoL assessment may be prognostic for CRC.
PMID- 27492455
TI - MicroRNA-15a inhibits the growth and invasiveness of malignant melanoma and
directly targets on CDCA4 gene.
AB - MicroRNAs can affect behaviors of tumor cells by modulating the expression of the
target genes that involve tumor growth, invasiveness, and death. The goal of this
research is to examine the effects of miR-15a on the proliferation and
invasiveness of malignant melanoma cells in vitro, as well as the therapeutic
effect of miR-15a in a mouse melanoma model. miR-15a displayed inhibitory effects
on proliferation and invasiveness of several malignant melanoma cell lines. miR
15a also caused cell cycle arrest at G1/G0 phase. miRNA 15a downregulated the
expressions of CDCA4 and AKT-3 in melanoma cell lines. In vivo, experiment showed
that miRNA 15a significantly retarded the growth of melanoma tumors in the mouse
model. The luciferase reporter assay demonstrated that miR15a can suppress gene
expression through the binding site in the 3 'UTR of CACD4, which is a bona fide
target of miRNA 15a. In conclusion, miRNA 15a suppressed the growth and
invasiveness of melanoma cells, suggesting that miRNA 15a may represent a viable
microRNA-based therapy against melanoma.
PMID- 27492456
TI - Extracellular HSP70-peptide complexes promote the proliferation of hepatocellular
carcinoma cells via TLR2/4/JNK1/2MAPK pathway.
AB - Heat shock protein 70 (HSP70) and HSP70-peptide complexes (HSP70-PCs) have been
implicated in the pathogenesis of multiple tumors in humans and have been
experimentally shown to increase the proliferation of cell lines derived from
hepatocellular carcinoma. The goal of this study was to elucidate the molecular
mechanisms through which extracellular HSP70/HSP70-PCs stimulate the
proliferation of hepatocellular carcinoma (HCC). The molecular mechanisms of
HSP70/HSP70-PC action were studied in the human hepatocellular carcinoma cell
lines HepG2 and Huh-7, as well as tumor tissue collected from patients with HCC
(n = 95). We found that HSP70/HSP70-PCs can stimulate the proliferation of HepG2
cells and that this effect is blocked by knocking down TLR2 and TLR4 expression
by RNA interference. A physical interaction between HSP70/HSP70-PCs and TLR2/4
was established using co-immunoprecipitation and pull-down assays.
Pharmacological inhibition of different branches of the MAPK intracellular
signaling pathway indicated that the extracellular HSP70/HSP70-PC effect was
mediated by the JNK1/2 signaling pathway within the cell. We also studied TLR2
and TLR expression at the protein and messenger RNA (mRNA) level in tumor and non
tumor tissue in patients with HCC (n = 95), finding that TLR2 and 4 are increased
in HCC tumor tissue and that the expression of TLR2 correlates with
clinicopathologic features of HCC. Our data conclusively demonstrates that
extracellular HSP70/HSP70-PCs can promote the proliferation of HCC cells through
activation of TLR2 and TLR4 and subsequent activation of the intracellular
JNK1/2/MAPK signaling pathway.
PMID- 27492457
TI - Fibroblast activation protein alpha is expressed by transformed and stromal cells
and is associated with mesenchymal features in glioblastoma.
AB - Glioblastomas are deadly neoplasms resistant to current treatment modalities.
Fibroblast activation protein (FAP) is a protease which is not expressed in most
of the normal adult tissues but is characteristically present in the stroma of
extracranial malignancies. FAP is considered a potential therapeutic target and
is associated with a worse patient outcome in some cancers. The FAP localization
in the glioma microenvironment and its relation to patient survival are unknown.
By analyzing 56 gliomas and 15 non-tumorous brain samples, we demonstrate
increased FAP expression in a subgroup of high-grade gliomas, in particular on
the protein level. FAP expression was most elevated in the mesenchymal subtype of
glioblastoma. It was neither associated with glioblastoma patient survival in our
patient cohort nor in publicly available datasets. FAP was expressed in both
transformed and stromal cells; the latter were frequently localized around
dysplastic blood vessels and commonly expressed mesenchymal markers. In a mouse
xenotransplantation model, FAP was expressed in glioma cells in a subgroup of
tumors that typically did not express the astrocytic marker GFAP. Endogenous FAP
was frequently upregulated and part of the FAP+ host cells coexpressed the CXCR4
chemokine receptor. In summary, FAP is expressed by several constituents of the
glioblastoma microenvironment, including stromal non-malignant mesenchymal cells
recruited to and/or activated in response to glioma growth. The limited
expression of FAP in healthy tissues together with its presence in both
transformed and stromal cells suggests that FAP may be a candidate target for
specific delivery of therapeutic agents in glioblastoma.
PMID- 27492458
TI - Disruption of clock gene expression in human colorectal liver metastases.
AB - The circadian timing system controls about 40 % of the transcriptome and is
important in the regulation of a wide variety of biological processes including
metabolic and proliferative functions. Disruption of the circadian clock could
have significant effect on human health and has an important role in the
development of cancer. Here, we compared the expression levels of core clock
genes in primary colorectal cancer (CRC), colorectal liver metastases (CRLM), and
liver tissue within the same patient. Surgical specimens of 15 untreated patients
with primary CRC and metachronous CRLM were studied. Quantitative real-time
polymerase chain reaction (qRT-PCR) was used to measure the expression of 10
clock genes: CLOCK, BMAL1, PER1, PER2, PER3, CRY1, CRY2, CSNK1E, TIM, TIPIN, and
2 clock-controlled genes: Cyclin-D1, and WEE1. Expression levels of 7 core clock
genes were downregulated in CRLM: CLOCK (p = 0.006), BMAL1 (p = 0.003), PER1 (p =
0.003), PER2 (p = 0.002), PER3 (p < 0.001), CRY1 (p = 0.002), and CRY2 (p <
0.001). In CRC, 5 genes were downregulated: BMAL1 (p = 0.02), PER1 (p = 0.004),
PER2 (p = 0.008), PER3 (p < 0.001), and CRY2 (p < 0.001). CSNK1E was upregulated
in CRC (p = 0.02). Cyclin-D1 and WEE1 were both downregulated in CRLM and CRC.
Related to clinicopathological factors, a significant correlation was found
between low expression of CRY1 and female gender, and low PER3 expression and the
number of CRLM. Our data demonstrate that the core clock is disrupted in CRLM and
CRC tissue from the same patient. This disruption may be linked to altered cell
cycle dynamics and carcinogenesis.
PMID- 27492459
TI - MicroRNA target for MACC1 and CYR61 to inhibit tumor growth in mice with
colorectal cancer.
AB - Cysteine-rich protein 61 (CYR61) and metastasis associated in colon cancer
(MACC1) protein promoted human colorectal cancer (CRC) cell metastasis and
closely related to the patient's prognosis in colorectal cancer. The purpose of
this article is to investigate whether CYR61 and MACC1 can serve as dual
potential targets for gene therapy of human CRC. In this study, microRNA (miRNA)
targeting for both CYR61 and MACC1 was used to investigate the mechanism and
therapeutic effects for CRC cells and mice with CRC. We observed that silencing
miRNA for CYR61 and MACC1 inhibited the epithelial-mesenchymal transition (EMT)
process, and co-treatment strengthened this effect. MTT assay showed that the
growth of colorectal tumor cells was decreased due to miRNA treatment. Apoptosis
assay revealed that miRNA for CYR61 and MACC1 promoted CRC cells apoptotic. The
animals' study results showed that the expression levels of CYR61 and MACC1 were
significantly decreased after miRNA-100 and miRNA-143 treatment, respectively.
The expression levels of apoptosis-promoting protein were increased significantly
after treatment with miRNA-100 and miRNA-143, which suggested that both miRNA-100
and miRNA-143 may induce apoptosis by mitochondria-dependent pathway. In
addition, metastasis and invasion assays showed that miRNA-100 and miRNA-143
treatment inhibited obviously migratory and invasive abilities of CRC cells.
Furthermore, our data also showed that the tumor growth was significantly
inhibited and survival rate of tumor-bearing mice was greatly improved by common
treatments of miRNA-100 and miRNA-143. In conclusion, the abilities of apoptosis,
metastasis, and invasion in CRC tumor cells were significantly suppressed by
miRNA-100 and miRNA-143 targeting CYR61 and MACC1, respectively. As a result,
CYR61 and MACC1 may serve as potential targets for gene therapy in human CRC
treatments.
PMID- 27492461
TI - Complete mitochondrial genome of the giant liver fluke Fascioloides magna
(Digenea: Fasciolidae) and its comparison with selected trematodes.
AB - BACKGROUND: Representatives of the trematode family Fasciolidae are responsible
for major socio-economic losses worldwide. Fascioloides magna is an important
pathogenic liver fluke of wild and domestic ungulates. To date, only a limited
number of studies concerning the molecular biology of F. magna exist. Therefore,
the objective of the present study was to determine the complete mitochondrial
(mt) genome sequence of F. magna, and assess the phylogenetic relationships of
this fluke with other trematodes based on the mtDNA dataset. FINDINGS: The
complete F. magna mt genome sequence is 14,047 bp. The gene content and
arrangement of the F. magna mt genome is similar to those of Fasciola spp.,
except that trnE is located between trnG and the only non-coding region in F.
magna mt genome. Phylogenetic relationships of F. magna with selected trematodes
using Bayesian inference (BI) was reconstructed based on the concatenated amino
acid sequences for 12 protein-coding genes, which confirmed that the genus
Fascioloides is closely related to the genus Fasciola; the intergeneric
differences of amino acid composition between the genera Fascioloides and
Fasciola ranged 17.97-18.24 %. CONCLUSIONS: The determination of F. magna mt
genome sequence provides a valuable resource for further investigations of the
phylogeny of the family Fasciolidae and other trematodes, and represents a useful
platform for designing appropriate molecular markers.
PMID- 27492462
TI - Preparation methods and applications behind alginate-based particles.
AB - INTRODUCTION: Alginate-based particles have emerged as one of the most
extensively searched drug delivery platforms due to their inherent properties,
including good biocompatibility and biodegradability. Moreover, the low price,
easy availability, natural origin, versatility and sol-gel transition properties,
make alginate an ideal candidate to produce particles with different
applications. Several techniques have been developed and optimized to prepare
microparticles and nanoparticles in order to achieve more rational, coherent,
efficient and cost-effective procedures. Alginate represents a suitable choice
concerning delivery systems' safety, and therefore alginate-based particles have
shown to be useful in the field of drug delivery with a special focus on
biological encapsulants. Area covered: This review will provide an overview of
alginate-based delivery systems, covering the innovative preparation methods of
the last decade, the advantages and disadvantages of the most used methods, their
wide diversity of applications and safety concerns. Expert opinion: The
progression of nanotechnology over the last decades has stimulated the refinement
of former microencapsulation methods and the exploration of new approaches
towards the submicron scale with increased attention being focused on the safety
of nanoparticles and product performance. Therefore, the design and optimization
of the preparation methods of alginate-based microparticles and nanoparticles as
well as their nontoxicity, biocompatibility and biodegradability to reach the
desired application have been widely explored.
PMID- 27492460
TI - MicroRNA-137 represses FBI-1 to inhibit proliferation and in vitro invasion and
migration of hepatocellular carcinoma cells.
AB - The pro-oncogene factor that binds to inducer of short transcripts-1 (FBI-1),
which is encoded by ZBTB7A gene and belongs to POK (POZ/BTB and KrUppel) protein
family, has been shown to enhance hepatocellular carcinoma (HCC) cells
proliferation and multi-drug resistance (MDR) process. However, the possibility
that FBI-1 is a therapeutic target for further HCC treatment remains poorly
determined. In the current study, two microRNA (miRNA) target prediction programs
(TargetScan and MiRanda) were used to identify miR-137 as a potential regulator
of FBI-1. Our results showed that expression of miR-137 was downregulated, while
FBI-1 was upregulated in clinical HCC specimens, compared with paired non-tumor
specimens. Overexpression of miR-137 via adenoviral vector inhibited the
proliferation and anchorage-independent growth of HCC cells, HepG2 and MHCC-97H.
Our data also showed that miR-137 repressed endogenous expression level of FBI-1,
as well as Notch-1 and Survivin. MiR-137 also inhibited in vitro invasion and
migration of HCC cells and attenuated their epithelial-mesenchymal transition
(EMT) process. Moreover, miR-137 suppressed the growth rate of HepG2 cells in
nude mice model. Overexpression of miR-137 via its adenoviral vector enhanced the
sensitivity of HepG2 cells to anti-tumor drugs and attenuated the MDR process of
a resistance cell line HepG2/adriamycin (ADR). Thus, FBI-1 downregulation
mediated by miR-137 overexpression may be a potential strategy for HCC treatment.
PMID- 27492463
TI - Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip:
lessons learned from failures and opportunities for the future.
AB - Osteoarthritis (OA) is the biggest unmet medical need among the many
musculoskeletal conditions and the most common form of arthritis. It is a major
cause of disability and impaired quality of life in the elderly. We review
several ambitious but failed attempts to develop joint structure-modifying
treatments for OA. Insights gleaned from these attempts suggest that these
failures arose from unrealistic hypotheses, sub-optimal selection of patient
populations or drug dose, and/or inadequate sensitivity of the trial endpoints.
The long list of failures has prompted a paradigm shift in OA drug development
with redirection of attention to: (1) consideration of the benefits of localized
vs systemic pharmacological agents, as indicated by the increasing number of
intra-articularly administered compounds entering clinical development; (2)
recognition of OA as a complex disease with multiple phenotypes, that may each
require somewhat different approaches for optimizing treatment; and (3) trial
enhancements based on guidance regarding biomarkers provided by regulatory
agencies, such as the Food and Drug Administration (FDA), that could be harnessed
to help turn failures into successes.
PMID- 27492465
TI - Cost utility modeling of early vs late total knee replacement in osteoarthritis
patients.
AB - : Given the dramatic increase in the number of total knee replacement (TKR)
surgeries in developed countries, the issue of the best time for surgery needs to
be addressed from an economic perspective. OBJECTIVE: To assess, from the
perspective of the healthcare payer, the cost-utility of two surgical strategies
in which knee replacement is performed at the early or late stage of the disease
in patients with knee osteoarthritis (OA). DESIGN: Patient data and evidence from
published literature on economic costs and outcomes in OA, including utilities,
non-pharmacological, pharmacological and surgical options, combined with
population life tables were entered in a Markov model of OA. The model
represented the lifetime experience of a cohort of patients following their
therapeutic management, discounting costs (euros) and utilities (quality-adjusted
life-years) at 4% annually. RESULTS: In the base-case scenario, early TKR cost
?6,624 more than late TKR (?76,223 vs ?69,599) with a 0.15 gain in QALYs (18.675
vs 18.524). This yielded an incremental cost-utility ratio (ICUR) of 43,631
?/QALY. Sensitivity analyses of the most influential uncertain parameters were
performed and did not modify the direction of the conclusions: early TKR cost
between ?3,655 and ?7,194 more than late TKR with a gain in QALYs between 0.15
and 0.39. The ICUR ranged from 17,131 ?/QALY to 48,241 ?/QALY. CONCLUSION: Our
data do not support the early TKR strategy over the late TKR strategy in knee OA
patients from a medico-economic perspective.
PMID- 27492464
TI - The association of waist circumference with walking difficulty among adults with
or at risk of knee osteoarthritis: the Osteoarthritis Initiative.
AB - OBJECTIVE: Excess weight is a known risk factor for functional limitation and
common in adults with knee osteoarthritis (OA). We asked to what extent high
waist circumference was linked with developing difficulty with walking speed and
distance over 4 years in adults with or at risk of knee OA. METHOD: Using data
from the Osteoarthritis Initiative (OAI), we employed World Health Organization
(WHO) categories for Body Mass Index (BMI) and waist circumference (small/medium
and large). Difficulty with speed was defined by slow gait: <1.2 m/s during a 20
m walk, and difficulty with distance was defined by an inability to walk 400 m.
We calculated risk ratios (RR) to examine the likelihood of developing difficulty
with distance and speed using obesity and waist circumference as predictors with
RRs adjusted for potential confounders (i.e., age, sex, race, education, physical
activity, and OA status). RESULTS: Participants with obesity and large waists
were 2.2 times more likely to have difficulty with speed at 4 years compared to
healthy weight and small/medium waisted participants (Adjusted RR 2.2 [95%
Confidence interval (CI) 1.6, 3.1], P < .0001). Participants with obesity and a
large waist circumference had 2.4 times the risk of developing the inability to
walk 400 m compared with those with a healthy BMI and small/medium waist
circumference (Adjusted RR 0.9 [95% CI 1.6, 3.7], P < .0001). CONCLUSIONS: Waist
circumference may be a main risk factor for developing difficulty with speed in
adults with or at risk of knee OA.
PMID- 27492466
TI - Comparative safety profile of hyaluronic acid products for knee osteoarthritis: a
systematic review and network meta-analysis.
AB - PURPOSE: Intra-articular (IA) hyaluronic acid (HA) is considered a safer
alternative to oral Non-Steroidal Antiinflammatory Drugs (NSAIDs) and opioids for
knee osteoarthritis (OA). A recent review raised potential safety concerns about
HA, warranting further review of safety outcomes. We examined the risks of HA
compared with IA placebo and investigated whether the risks vary among individual
HA preparations. METHODS: We searched all relevant databases from inception to
October 2015 and sought unpublished data. We included all knee OA trials which
compared any of the 18 HA products and reported on adverse events (AEs) and
withdrawals. We calculated odds ratios for safety data reported at the longest
follow-up. Network meta-analysis was performed using a Bayesian hierarchical
random effects model for mixed multiple treatment comparisons. RESULTS: We
identified 74 studies involving 13,032 participants aged between 45 and 75 years.
The proportion of women ranged from 28% to 100%. The overall incidence of local
reactions reported across all products was 8.5%. Commonly reported AEs were
transient local reactions, such as pain, swelling and arthralgia, which subsided
rapidly. None of the HA products were statistically significantly different from
IA placebo or from each other with regard to incidence of AEs. Three treatment
related serious adverse events (SAEs) were reported among 9214 participants.
CONCLUSIONS: Given the very low incidence of any particular AEs, we conclude that
HA products are relatively well tolerated. These products have a similar safety
profile compared to each other. This information along with the comparative
effectiveness profile and relative cost would be helpful for clinicians in
delivering individualized patient care.
PMID- 27492467
TI - The influence of weather on the risk of pain exacerbation in patients with knee
osteoarthritis - a case-crossover study.
AB - OBJECTIVE: To quantify the risk of knee pain exacerbation associated with
temperature, relative humidity, air pressure and precipitation in persons with
knee osteoarthritis. METHOD: A web-based case-crossover study was conducted.
Participants with a diagnosis of symptomatic, radiographic knee osteoarthritis
were measured at baseline and followed for 3 months. Participants were instructed
to log on to the study website if they perceived experiencing knee pain
exacerbation (hazard period). Pain exacerbation was defined as an increase of >=2
on a 0-10 numeric rating scale (NRS) from the participant's mildest pain reported
at baseline. A time-stratified case-crossover study was conducted to anchor the
corresponding hazard date to four control periods within a particular 35-day
interval. Data on maximum and minimum temperature ( degrees C), relative humidity
(%), barometric pressure (hPa) and precipitation (mm) were obtained for the
hazard and control periods from the publicly available meteorological database of
the Australian Bureau of Meteorology. The associations were assessed using
conditional logistic regression. RESULTS: Of the 345 participants recruited, 171
participants (women: 64%, mean age: 62 years, mean BMI: 30.2 kg/m2) experienced
at least one episode of pain exacerbation, yielding 1,425 observations included
in the analyses. There was no apparent association between temperature, relative
humidity, air pressure or precipitation and risk of knee pain exacerbation.
CONCLUSION: Despite anecdotal reports from patients, change in weather factors
does not appear to influence the risk of pain exacerbation in persons with knee
osteoarthritis. Additional studies should quantify the association of weather and
risk of pain exacerbation in regions with more extreme weather conditions.
PMID- 27492468
TI - Mating Disruption as a Suppression Tactic in Programs Targeting Regulated
Lepidopteran Pests in US.
AB - Mating disruption, the broadcast application of sex-attractant pheromone to
reduce the ability of insects to locate mates, has proven to be an effective
method for suppressing populations of numerous moth pests. Since the conception
of mating disruption, the species-specificity and low toxicity of pheromone
applications has led to their consideration for use in area-wide programs to
manage invasive moths. Case histories are presented for four such programs where
the tactic was used in the United States: Pectinophora gossypiella (pink
bollworm), Lymantria dispar (gypsy moth), Epiphyas postvittana (light brown apple
moth), and Lobesia botrana (European grapevine moth). Use of mating disruption
against P. gossypiella and L. botrana was restricted primarily to agricultural
areas and relied in part (P. gossypiella) or wholly (L. botrana) on hand-applied
dispensers. In those programs, mating disruption was integrated with other
suppression tactics and considered an important component of overall efforts that
are leading toward eradication of the invasive pests from North America. By
contrast, L. dispar and E. postvittana are polyphagous pests, where pheromone
formulations have been applied aerially as stand-alone treatments across broad
areas, including residential neighborhoods. For L. dispar, mating disruption has
been a key component in the program to slow the spread of the infestation of this
pest, and the applications generally have been well tolerated by the public. For
E. postvittana, public outcry halted the use of aerially applied mating
disruption after an initial series of treatments, effectively thwarting an
attempt to eradicate this pest from California. Reasons for the discrepancies
between these two programs are not entirely clear.
PMID- 27492470
TI - Core competencies for UK occupational health nurses: a Delphi study.
AB - Background: Occupational health nurses (OHNs) play a pivotal role in the delivery
of occupational health (OH) services. Specific competency guidance has been
developed in a number of countries, including the UK. While it is acknowledged
that UK OHN practice has evolved in recent years, there has been no formal
research to capture these developments to ensure that training and curricula
remain up-to-date and reflect current practice. Aims: To identify current
priorities among UK OHNs of the competencies required for OH practice. Methods: A
modified Delphi study undertaken among representative OHN networks in the UK.
This formed part of a larger study including UK and international occupational
physicians. The study was conducted in two rounds using a questionnaire based on
available guidance on training competencies for OH practice, the published
literature, expert panel reviews and conference discussions. Results: Consensus
among OHNs was high with 7 out of the 12 domains scoring 100% in rating. 'Good
clinical care' was the principal domain ranked most important, followed by
'general principles of assessment & management of occupational hazards to
health'. 'Research methods' and 'teaching & educational supervision' were
considered least important. Conclusions: This study has established UK OHNs'
current priorities on the competencies required for OH practice. The timing of
this paper is opportune with the formal launch of the Faculty of Occupational
Health Nursing planned in 2018 and should inform the development of competency
requirements as part of the Faculty's goals for standard setting in OHN education
and training.
PMID- 27492469
TI - Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational
Perspectives.
AB - Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder
resulting in fractures, deformity, functional impairment, and pain. It arises
from post-zygotic somatic activating mutations in GNAS, in the cAMP-regulating
transcript alpha-subunit, Gsalpha. Constitutive Gs signaling results in
activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton,
this leads to the development of FD lesions with abnormal bone matrix,
trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may
occur in isolation or in combination with extraskeletal manifestations, including
hyperfunctioning endocrinopathies and cafe-au-lait macules, termed McCune
Albright syndrome (MAS). This review summarizes current clinical and
translational perspectives in FD/MAS, with an emphasis on FD pathogenesis,
natural history, pre-clinical and clinical investigation, and future directions.
PMID- 27492471
TI - Medical surveillance for occupational asthma-how are cases detected?
AB - Background: In Finland, medical surveillance, including spirometry, is
periodically performed for workers who are exposed to agents capable of causing
occupational asthma (OA). Although it has been shown that surveillance can detect
OA at an early stage, few studies have assessed its benefits or the role of
surveillance spirometry. Aims: To assess the role of surveillance and spirometry
in detecting OA and to evaluate the quality of spirometry. Methods: We
retrospectively reviewed the medical files of patients in health surveillance
programmes who were diagnosed with sensitizer-induced OA at the Finnish Institute
of Occupational Health in 2012-14. We collected information on work exposure,
respiratory symptoms, healthcare visits that initiated the diagnostic process,
first spirometry and other diagnostic tests. Results: Sixty files were reviewed.
Medical surveillance detected 11 cases (18%) and 49 cases (82%) were detected at
doctors' appointments that were not related to surveillance. The median delay
from the onset of asthma symptoms to diagnosis was 2.2 years. Delay did not
differ between these groups. No cases were detected on the basis of abnormal
spirometry without respiratory symptoms. However, five patients (8%) initially
reported solely work-related rhinitis symptoms. Spirometry was normal in half of
the cases and quality criteria were fulfilled in 86% of the tests. Conclusions:
Fewer than one in five OA cases were detected through medical surveillance.
Investigations were initiated by respiratory symptoms. No asymptomatic worker was
referred because of abnormal spirometry. Our results highlight the importance of
work-related nasal symptoms in detecting OA.
PMID- 27492472
TI - [Clinical features of delayed endolymphatic hydrops and intralabyrinthine
schwannoma : An imaging-confirmed comparative case series. German version].
AB - BACKGROUND: The aim of this study was to compare the clinical history and the
findings in audiovestibular function tests in patients suffering from
intralabyrinthine schwannoma or delayed endolymphatic hydrops (DEH). PATIENTS AND
METHODS: Five patients diagnosed with intralabyrinthine schwannoma by magnetic
resonance imaging (MRI) and five patients diagnosed with DEH by locally enhanced
inner ear MRI (LEIM) were retrospectively studied. RESULTS: All patients with
intralabyrinthine schwannoma or DEH initially presented with hearing loss.
Vertigo occurred in two patients with intralabyrinthine schwannoma and in all
patients with DEH. While audiometry achieved poorer results for patients with
intralabyrinthine schwannomas, vestibular function tests revealed normal results
in about half of the patients in both groups. CONCLUSION: Patients with
intralabyrinthine schwannomas may present with clinical symptoms similar to
patients suffering from other inner ear disorders like delayed endolymphatic
hydrops and may obtain similar findings in audiovestibular function tests. High
resolution MR imaging with locally applied contrast agent may provide evidence of
both underlying pathologies.
PMID- 27492473
TI - Clinical features of delayed endolymphatic hydrops and intralabyrinthine
schwannoma : An imaging-confirmed comparative case series. English version.
AB - BACKGROUND: The aim of this study was to compare the clinical history and
audiovestibular function test results of patients suffering from
intralabyrinthine schwannoma or delayed endolymphatic hydrops (DEH). PATIENTS AND
METHODS: Five patients diagnosed with intralabyrinthine schwannoma by magnetic
resonance imaging (MRI) and five patients diagnosed with DEH by locally enhanced
inner ear MRI (LEIM) were retrospectively studied. RESULTS: All patients with
intralabyrinthine schwannoma or DEH initially presented with hearing loss.
Vertigo occurred in two patients with intralabyrinthine schwannoma and in all
patients with DEH. While audiometry achieved poorer results for patients with
intralabyrinthine schwannomas, vestibular function tests revealed normal results
in about half of the patients in both groups. CONCLUSION: Patients with
intralabyrinthine schwannomas may present with clinical symptoms similar to
patients suffering from other inner ear disorders such as delayed endolymphatic
hydrops and they may obtain similar findings in audiovestibular function tests.
High-resolution magnetic resonance imaging with locally applied contrast agent
may provide evidence of both underlying pathologies.
PMID- 27492474
TI - Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive
immune systems.
AB - The generation of genetic variation (somatic hypermutation) is an essential
process for the adaptive immune system in vertebrates. We demonstrate the
targeted single-nucleotide substitution of DNA using hybrid vertebrate and
bacterial immune systems components. Nuclease-deficient type II CRISPR/Cas9
(clustered regularly interspaced short palindromic repeats/CRISPR-associated) and
the activation-induced cytidine deaminase (AID) ortholog PmCDA1 were engineered
to form a synthetic complex (Target-AID) that performs highly efficient target
specific mutagenesis. Specific point mutation was induced primarily at cytidines
within the target range of five bases. The toxicity associated with the nuclease
based CRISPR/Cas9 system was greatly reduced. Although combination of nickase
Cas9(D10A) and the deaminase was highly effective in yeasts, it also induced
insertion and deletion (indel) in mammalian cells. Use of uracil DNA glycosylase
inhibitor suppressed the indel formation and improved the efficiency.
PMID- 27492476
TI - Continental patterns of submarine groundwater discharge reveal coastal
vulnerabilities.
AB - Submarine groundwater discharge (SGD) delivers water and dissolved chemicals from
continents to oceans, and its spatial distribution affects coastal water quality.
Unlike rivers, SGD is broadly distributed and relatively difficult to measure,
especially at continental scales. We present spatially resolved estimates of
fresh (land-derived) SGD for the contiguous United States based on historical
climate records and high-resolution hydrographic data. Climate controls regional
patterns in fresh SGD, while coastal drainage geometry imparts strong local
variability. Because the recharge zones that contribute fresh SGD are densely
populated, the quality and quantity of fresh SGD are both vulnerable to
anthropogenic disturbance. Our analysis unveils hot spots for contaminant
discharge to marine waters and saltwater intrusion into coastal aquifers.
PMID- 27492475
TI - Specification of tissue-resident macrophages during organogenesis.
AB - Tissue-resident macrophages support embryonic development and tissue homeostasis
and repair. The mechanisms that control their differentiation remain unclear. We
report here that erythro-myeloid progenitors in mice generate premacrophages
(pMacs) that simultaneously colonize the whole embryo from embryonic day 9.5 in a
chemokine-receptor-dependent manner. The core macrophage program initiated in
pMacs is rapidly diversified as expression of transcriptional regulators becomes
tissue-specific in early macrophages. This process appears essential for
macrophage specification and maintenance, as inactivation of Id3 impairs the
development of liver macrophages and results in selective Kupffer cell deficiency
in adults. We propose that macrophage differentiation is an integral part of
organogenesis, as colonization of organ anlagen by pMacs is followed by their
specification into tissue macrophages, hereby generating the macrophage diversity
observed in postnatal tissues.
PMID- 27492478
TI - Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide
silencing.
AB - The Xist long noncoding RNA orchestrates X chromosome inactivation, a process
that entails chromosome-wide silencing and remodeling of the three-dimensional
(3D) structure of the X chromosome. Yet, it remains unclear whether these changes
in nuclear structure are mediated by Xist and whether they are required for
silencing. Here, we show that Xist directly interacts with the Lamin B receptor,
an integral component of the nuclear lamina, and that this interaction is
required for Xist-mediated silencing by recruiting the inactive X to the nuclear
lamina and by doing so enables Xist to spread to actively transcribed genes
across the X. Our results demonstrate that lamina recruitment changes the 3D
structure of DNA, enabling Xist and its silencing proteins to spread across the X
to silence transcription.
PMID- 27492480
TI - Auto-brewery syndrome: Ethanol pseudo-toxicity in diabetic and hepatic patients.
AB - Endogenous alcohol has been applied for spontaneous ethanol production via
different metabolic pathways of the human body. Auto-brewery syndrome describes
the patients with alcohol intoxication after ingesting carbohydrate-rich meals.
The main objective of this study is to investigate the effect of diabetes
mellitus (DM), liver cirrhosis (LC) and presence of both (DM and LC) on blood
alcohol concentration (BAC) especially after carbohydrate ingestion. BAC has been
measured by headspace gas chromatography-mass spectrometry in three groups of
humans namely control, DM, LC and both (DM and LC) groups. The results showed
that BAC in control group was 0.01-.3 mg/dL with mean 0.3 +/- 0.41 mg/dL. In
patients with DM, BAC is significantly higher than that of control group 4.85 +/-
3.96 mg/dL. In patients with LC, BAC was 3.45 +/- 2.65 mg/dL. In patients with
both DM and LC, BAC increases to reach 10.88 +/- 5.36 mg/dL. Endogenous ethanol
production appears to increase in DM and LC. Also, it increased much more in
patients with both diseases, but it did not reach toxic levels. On comparing BAC
and blood glucose level in each group, all groups show insignificant correlations
( p > 0.05).
PMID- 27492477
TI - Protective efficacy of multiple vaccine platforms against Zika virus challenge in
rhesus monkeys.
AB - Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and
has been causally associated with fetal microcephaly. The development of a safe
and effective ZIKV vaccine is therefore an urgent global health priority. Here we
demonstrate that three different vaccine platforms protect against ZIKV challenge
in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific
neutralizing antibodies and completely protected monkeys against ZIKV strains
from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys
also conferred passive protection in adoptive transfer studies. A plasmid DNA
vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector
vaccine, both expressing ZIKV premembrane and envelope, also elicited
neutralizing antibodies and completely protected monkeys against ZIKV challenge.
These data support the rapid clinical development of ZIKV vaccines for humans.
PMID- 27492481
TI - Insurance statements related to regional anaesthesia: A French database analysis.
AB - BACKGROUND: Adverse events in the perioperative period remain frequent, occurring
in about 30% of the hospital admission and may be avoidable in nearly 50% of
cases. Improving safety needs a continuous assessment of the risk level. MATERIAL
AND METHODS: Data from the MACSF-Sou medical insurance company, including all the
statements declared by anaesthesiologists and intensivists, were analyzed
retrospectively by three experts, senior anaesthesiologists, of the SFAR, the
French society of anesthesia and intensive care (Societe francaise d'anesthesie
reanimation) to describe the risk associated with regional anaesthesia. RESULTS:
One hundred and sixty-four events were analyzed, involving young patients (mean
age of 48.3+/-15years; sex ratio: 0.57). The most involved surgical specialties
were: orthopaedic surgery (61%) and obstetric surgery (13.4%). Reported events
were predominantly peripheral nerve injury (64.6%). Mechanical complications of
puncture (pneumothorax, haemothorax, complications of axial punctures) accounted
for approximately 15% of events, infection for 11%. The revelation was
predominant in the postoperative course (137 cases, 83.6%), particularly after
the release of the operating room in over 47% of cases, including 39 cases (22%)
after discharge from the hospital. CONCLUSION: Collaboration with insurance
companies allows a relevant approach of the perioperative risk. In most cases,
liability related to regional anaesthesia involved young patients in the
perioperative course of scheduled surgery. One of the future challenges in
managing, the anaesthetic and perioperative risks should be to invest more
accurately the postoperative care both in the hospital or ambulatory settings.
PMID- 27492479
TI - Modulatory role of betulinic acid in N-nitrosodimethylamine-induced hepatorenal
toxicity in male Wistar rats.
AB - N-nitrosodimethylamine (NDMA) is a toxicant found in foods and drinking water.
Several synthetic agents used in alleviation of NDMA toxicity have been
associated with serious side effects. Therefore, a safe and less toxic agent is
desirable. In this study, betulinic acid (BA), a triterpenoid antioxidant, is
proposed as a better and alternative agent to modulate NDMA-induced toxicity.
Twenty-four Wistar rats were assigned into four groups of six rats each and
treated with normal saline (control), BA (25 mg/kg), NDMA (5 mg/kg) and (BA +
NDMA). BA was given by oral gavage for 14 consecutive days, while NDMA was
administered intraperitoneally on days 7 and 12. Results showed that
administration of NDMA significantly ( p < 0.05) elevated the activities of serum
alanine aminotransferase (ALT), aspartate aminotransferase and gamma-glutamyl
transferase by 51%, 48% and 81%, respectively. Also, NDMA intoxication
significantly ( p < 0.05) increased the levels of serum urea and creatinine by
64% and 82%, respectively, and decreased urinary creatinine by 67%. In addition,
administration of NDMA significantly ( p < 0.05) increased the levels of hepatic
and renal DNA fragmentation by 44% and 61%, respectively, relative to control.
The number of micronucleated polychromatic erythrocytes (mnPCEs) in NDMA-treated
rats (11.1 +/- 2.6 mnPCE/1000PCE) was significantly higher than control (4.3 +/-
1.1 mnPCE/1000 PCE). Immunohistochemistry revealed strong expressions of Bcl-2
and nuclear p53 in NDMA-intoxicated rats. Interestingly, pretreatment with BA
significantly ( p < 0.05) ameliorated NDMA-induced changes in serum biochemical
indices, mnPCEs, DNA fragmentation and expressions of Bcl-2 and p53 proteins.
These findings suggest that BA protects against NDMA-induced toxicity via anti
oxidative and anti-apoptotic activities.
PMID- 27492482
TI - Prescription Opioid Abuse and its Potential Role in Gross Dental Decay.
AB - INTRODUCTION: Prescription opioid abuse may have adverse dental effects that are
irreversible, leaving younger populations with substantially decayed dentitions.
This article explores the damaging effects of three years of prescription opioid
abuse to a twenty-six-year-old's dentition and oral health. CASE PRESENTATION: A
twenty-six-year-old Caucasian male presented to the University of Pennsylvania
School of Dental Medicine with a past medical history of Percocet(r) abuse. He
was consuming approximately twenty tablets per day for three years, and he had
neglected to visit a dentist for over five years before arriving to the School of
Dental Medicine. Management and Outcome: Intraoral examination revealed gross
generalized decay along with generalized plaque accumulation. He was diagnosed
with severe plaque induced gingivitis with localized chronic periodontitis and
xerostomia. The dental treatment for this patient included periodontal
maintenance and control, caries excavation, root canal therapy, extractions of
non-restorable teeth, and continuous dental education. DISCUSSION: Prescription
opioids are addictive, have high abuse potential, and dentists contribute to this
problem by overprescribing these drugs.
PMID- 27492483
TI - Automatic Identification of Physical Activity Intensity and Modality from the
Fusion of Accelerometry and Heart Rate Data.
AB - BACKGROUND: Physical activity (PA) is essential to prevent and to treat a variety
of chronic diseases. The automated detection and quantification of PA over time
empowers lifestyle interventions, facilitating reliable exercise tracking and
data-driven counseling. METHODS: We propose and compare various combinations of
machine learning (ML) schemes for the automatic classification of PA from multi
modal data, simultaneously captured by a biaxial accelerometer and a heart rate
(HR) monitor. Intensity levels (low / moderate / vigorous) were recognized, as
well as for vigorous exercise, its modality (sustained aerobic / resistance /
mixed). In total, 178.63 h of data about PA intensity (65.55 % low / 18.96 %
moderate / 15.49 % vigorous) and 17.00 h about modality were collected in two
experiments: one in free-living conditions, another in a fitness center under
controlled protocols. The structure used for automatic classification comprised:
a) definition of 42 time-domain signal features, b) dimensionality reduction, c)
data clustering, and d) temporal filtering to exploit time redundancy by means of
a Hidden Markov Model (HMM). Four dimensionality reduction techniques and four
clustering algorithms were studied. In order to cope with class imbalance in the
dataset, a custom performance metric was defined to aggregate recognition
accuracy, precision and recall. RESULTS: The best scheme, which comprised a
projection through Linear Discriminant Analysis (LDA) and k-means clustering, was
evaluated in leave-one-subject-out cross-validation; notably outperforming the
standard industry procedures for PA intensity classification: score 84.65 %,
versus up to 63.60 %. Errors tended to be brief and to appear around transients.
CONCLUSIONS: The application of ML techniques for pattern identification and
temporal filtering allowed to merge accelerometry and HR data in a solid manner,
and achieved markedly better recognition performances than the standard methods
for PA intensity estimation.
PMID- 27492484
TI - Treatment with cytokine thymic stromal lymphopoietin short hairpin RNA
substantially reduces TGF-beta1-induced interstitial cellular fibrosis.
AB - Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic
inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise
from such inflammation. It remains unclear, however, whether TSLP plays any role
in the occurrence of renal fibrosis, so this study investigated that possibility.
An in vitro fibrosis model was established by treating normal rat kidney
fibroblast (NRK-49F) cells with transforming growth factor-beta1 (TGF-beta1),
after which the levels of various fibrogenic markers (e.g., fibronectin) and
downstream fibrogenic signal proteins (e.g., smad 7) were investigated. Also,
TSLP shRNA was used to silence the effects of TSLP, while an ELISA was conducted
to evaluate the fibronectin secretions. The level of fibronectin in the NRK-49F
cells was dose- and time-dependently increased by the administration of exogenous
TSLP (P<0.05). TSLP also significantly increased the level of fibrosis signaling,
in addition to inducing a marked decrease in the down-regulation of Smad7.
Interestingly, the application of TSLP shRNA caused a stark reversal of the TGF
beta1-induced cellular fibrosis while simultaneously leading to the suppression
of fibronectin and fibrogenic signal proteins. Taken together, these observations
provide insights into how extracellular matrices develop and could thus lead to
potential therapeutic interventions for the suppression of renal fibrosis.
PMID- 27492486
TI - Transition and Dialectic: A Farewell, A Big Thank You, Some Medical Ethics and
Some Reproduction.
PMID- 27492485
TI - Divergent effects of Porcupine and Wntless on WNT1 trafficking, secretion, and
signaling.
AB - Loss-of-function studies have identified Porcupine (PORCN) and Wntless (WLS) as
essential mediators of Wnt secretion and signaling. Whereas PORCN is thought to
palmitoylate Wnt proteins, WLS is believed to transport palmitoylated Wnt
proteins to the cell surface. However, little is known about how these two
proteins cooperate to regulate Wnt palmitoylation, trafficking, secretion, and
signaling. We first investigated possible interactions between PORCN, WLS, and
WNT1, by carrying out co-immunoprecipitation studies. These studies demonstrate
the existence of a complex containing PORCN and WLS. They further show that PORCN
and WLS compete for binding to WNT1. Then, we used gain-of-function studies to
investigate the cooperation between PORCN and WLS as well as possible biochemical
interactions between PORCN, WLS, and WNT1. Consistent with the proposed roles for
PORCN and WLS, we show that overexpression of PORCN promotes palmitoylation of
WNT1 while overexpression of WLS does not. Overexpression of PORCN enhances the
ability of WLS to promote WNT1 trafficking to the cell surface as well as
secretion, but decreases the ability of WLS to activate WNT1 signaling in target
cell. These observations suggest that the levels of WNT1 on the cell surface and
in the media are not the sole determinants of the activation of Wnt signaling in
target cells.
PMID- 27492487
TI - The impact of fragility fractures on work and characteristics associated with
time to return to work.
AB - : We examined the impact of fragility fractures on the work outcomes of employed
patients. The majority successfully returned to their previous jobs in a short
amount of time, and productivity loss at work was low. Our findings underscore
the fast recovery rates of working fragility fracture patients. INTRODUCTION: The
purpose of this study is to describe the impact of fragility fractures on the
work outcomes of patients who were employed at the time of their fracture.
METHODS: A self-report anonymous survey was mailed to fragility fracture patients
over 50 who were screened as part of the quality assurance programs of fracture
clinics across 35 hospitals in Ontario, Canada. Measures of return to work (RTW),
at-work productivity loss (Work Limitations Questionnaire), and sociodemographic,
fracture-related, and job characteristics were included in the survey. Kaplan
Meier estimates of the cumulative proportion of patients still off work were
computed. Factors associated with RTW time following a fragility fracture were
examined using Cox proportional hazards modeling. RESULTS: Of 275 participants,
242 (88 %) returned to work. Of these, the median RTW time was 20.5 days. About
86 % returned to the same job, duties, and hours as before their injury. Among
full-time workers, the median number of lost hours due to presenteeism was 2.9 h
(Q1-Q3 0.4-8.1 h). The median cost of presenteeism was $75.30 based on the month
prior to survey completion. In multivariable analyses, female gender, needing
surgery, and medium/heavy work requirements were associated with longer RTW time.
Earlier RTW time was associated with elbow fracture and feeling completely better
at time of survey completion. CONCLUSIONS: The majority of fragility fracture
patients successfully returned to their previous jobs in a short amount of time,
and productivity loss at work was low. Our findings underscore their fast
recovery rates and give reason for optimism regarding the resilience of this
population.
PMID- 27492488
TI - Mothers' views of their preschool child's screen-viewing behaviour: a qualitative
study.
AB - BACKGROUND: Research on screen-viewing in preschool children has predominantly
focused on television viewing. The rapid development of mobile devices (e.g.
tablets, smart phones and e-readers) and the increase in their use by preschool
children means there is a need to understand how and why these devices are used
by this age group. The aim of this study was to explore mothers' views of their
preschool children's screen viewing behaviour (including mobile devices) and
investigate how preschool children use different screen-viewing devices. METHODS:
One-to-one, semi-structured interviews with mothers of preschool children (aged
between 2 and 4 years old). Mothers were recruited through preschools, nurseries,
and mother and toddler groups located within four areas of varying socio-economic
status within Bristol, UK. Data were analysed thematically using a framework
approach. RESULTS: Twenty-six mothers were interviewed. Mobile devices were
regularly used as a form of screen-viewing for most children but were used on an
ad hoc basis rather than being a habitual activity. The reasons and influences of
mobile device use described by mothers were similar to that of television
viewing. However, the portability of mobile devices meant that they were often
used outside of the home as a distraction tool. Their multi-functionality meant
that they could be used as a portable television, or for purposeful learning
through educational games and applications. Some mothers showed concerns over
mobile device use by their child, whilst others felt it was an important and
useful educational tool. Although the majority of mothers felt they needed to set
rules and restrictions for mobile device use, many mothers felt that they are
also a necessary and unavoidable part of life. CONCLUSIONS: Mothers in this study
suggested that mobile device use by preschool children is common. More research
is needed to determine the impact of mobile device use in preschool children, how
much time preschool children spend using mobile devices and which activities
their use may be replacing.
PMID- 27492489
TI - Imaging features of iBalance, a new high tibial osteotomy: what the radiologist
needs to know.
AB - OBJECTIVE: To describe the post-surgical imaging appearance and complications of
high tibial osteotomy in patients with the iBalance implant system (iHTO;
Arthrex, Naples, FL, USA). MATERIALS AND METHODS: Retrospective, institutional
review board-approved, Health Insurance Portability and Accountability Act
compliant review of imaging after 24 iBalance procedures was performed with
attention to: correction of varus malalignment, healing at the osteotomy site,
resorption of the osteoinductive compound, and complications. RESULTS: Immediate
correction of the varus deformity was present in all cases. Lobular radiolucency
was present in all cases, more pronounced on the lateral knee radiograph,
simulating infection or erosive disease. Four radiographic signs of healing were
observed: blurring at the opposing osteotomy bony margins and at the
osteoinductive compound and the adjacent bone interface, callus formation, and
resorption of the osteoinductive compound. Complications were present in 33 % of
cases, including fracture through the lateral tibial cortex (21 %), genu varum
recurrence (8 %), painful exuberant bone formation (4 %), persistent pain,
requiring total knee arthroplasty (4 %), and non-union (after >6 months' follow
up), with suspected infection (4 %). CONCLUSION: Radiologists should be aware of
the normal radiographic appearance following iBalance high tibial osteotomy,
which may be confused with infection. Radiologists should also be aware of
potential post-operative complications and compare all post-operative radiographs
with the immediate post-operative examination to detect collapse of the osteotomy
site and recurrence of varus angulation.
PMID- 27492490
TI - The effects of the Norwegian Coordination Reform on the use of rehabilitation
services: panel data analyses of service use, 2010 to 2013.
AB - BACKGROUND: In 2012 the Norwegian Coordination Reform was implemented. The main
motivation was to encourage municipalities to expand local, primary health care
services. From 2012 to 2014, under the Municipal Co-Financing regime,
municipalities were obliged to cover 20 % of the costs of health services
provided at the specialist (hospital) level. Importantly, use of rehabilitation
services in private institutions was not part of the cost-sharing mechanism of
Municipal Co-Financing. Rehabilitation services may be seen as quite similar in
nature whether they be provided by municipalities, hospitals or private
institutions. Thus, with rehabilitation patients readily "transferrable" between
levels, the question is whether the reform brought with it a sought after shift
towards more municipal rehabilitation and less specialist rehabilitation.
METHODS: Data from the Norwegian Patient Register and from Statistics
Norway/KOSTRA were utilized to gauge annual expenditures and inputs in
specialist, municipal and private institution rehabilitation services
respectively. Fixed effects and first difference regression analyses for the
period 2010-2013 were carried out to account for certain time-invariant traits of
municipalities and/or hospital regions, and results were adjusted for
contemporaneous trends in local needs. RESULTS: Expenditures in specialist
rehabilitation services declined sharply (typically by 8-10 %) from 2011 (pre
reform) to 2012 (post-reform), while expenditures in private rehabilitation
services rose markedly in the same period (typically by 42-44 %). The results do
not suggest any general expansion of municipal rehabilitation services.
CONCLUSIONS: The results of the analyses suggest that municipalities shift away
from the use of specialist rehabilitation services and towards the use of
rehabilitation services in private institutions since the latter becomes
relatively cheaper (free-of charge) than both municipal and specialist services
in post-reform periods (as specialist services come at a cost to municipalities
post-reform). While the main goal of the reform has not materialized the results
nevertheless suggest that incentives (of cost-shifting) do play a significant
role in rehabilitation service use.
PMID- 27492491
TI - Is high waist circumference and body weight associated with high blood pressure
in Iranian primary school children?
AB - INTRODUCTION AND OBJECTIVES: The prevalence of overweight, abdominal obesity and
hypertension among children has increased worldwide including Iran over several
decades. We carried out a study to provide current estimates of the prevalence
and trends of hypertension, overweight and obesity along with the relationship
between weight status and hypertension in Iranian school-children. METHOD: This
study was carried out among 1184 fifth-grade students, whose ages ranged from 11
to 14 years. Body weight, body mass index (BMI), height and waist circumference
(WC), systolic (SBP) and diastolic blood pressure (DBP) were measured. RESULTS:
22.04 and 5.32 % of students were overweight and obese, respectively. The
prevalence of overweight and obesity was significantly higher among girls than
boys (all p = 0.02), whereas the prevalence of hypertension was significantly
higher in boys than girls (p = 0.001). Although 27 % of boys and 24.32 % of girls
had abdominal obesity, no significant associations were reported between
abdominal obesity and sex (p = 0.12). The prevalence of hypertension in children
with normal weight, overweight and obesity, was 3, 9.7 and 17.8 %, respectively
(p < 0.01). We have obtained that the mean values of weight and WC were
significantly higher in boys than girls. Based on linear regression, every 1 cm
increase in abdominal circumference leads to an estimated DBP and SBP increase of
0.173 and 0.164 mmHg, respectively (p < 0.05). CONCLUSIONS: This study showed a
high prevalence of hypertension and obesity in a school-based population in
Tehran, Iran, in which the prevalence of hypertension was significantly and
positively correlated with weight and WC.
PMID- 27492492
TI - [Adaptation to physical activity and mental stress in the context of pain :
Psychobiological aspects].
AB - The genesis of chronic pain is predominantly explained by a multidimensional pain
model approach that is based on the dysfunctional influence of biological,
psychological and social variables as key risk factors inducing aberrant long
term changes. Biological facets comprise adaptation processes on the neuronal,
musculoskeletal and (psycho) biological level that can be influenced by physical
training or psychosocial factors, such as stress. These factors can play a
causative role in developing dysfunctional adaptation mechanisms, which in turn
prepare the biological ground to facilitate negative long-term changes in the
peripheral and central nervous systems. Hence, these processes can be assumed to
be fundamentally involved in the transition from acute to chronic and persistent
pain. The aim of this review article is to discuss hypotheses for the genesis of
chronic pain and possible treatment strategies. Selected research results about
maladaptive processes in chronic pain due to psychological stress and physical
activity are presented in order to inspire discussions about the ideal dose
response relationship of physical activity and the combination of different
therapeutic concepts.
PMID- 27492493
TI - Ultrafast acousto-optic mode conversion in optically birefringent ferroelectrics.
AB - The ability to generate efficient giga-terahertz coherent acoustic phonons with
femtosecond laser makes acousto-optics a promising candidate for ultrafast light
processing, which faces electronic device limits intrinsic to complementary metal
oxide semiconductor technology. Modern acousto-optic devices, including optical
mode conversion process between ordinary and extraordinary light waves (and vice
versa), remain limited to the megahertz range. Here, using coherent acoustic
waves generated at tens of gigahertz frequency by a femtosecond laser pulse, we
reveal the mode conversion process and show its efficiency in ferroelectric
materials such as BiFeO3 and LiNbO3. Further to the experimental evidence, we
provide a complete theoretical support to this all-optical ultrafast mechanism
mediated by acousto-optic interaction. By allowing the manipulation of light
polarization with gigahertz coherent acoustic phonons, our results provide a
novel route for the development of next-generation photonic-based devices and
highlight new capabilities in using ferroelectrics in modern photonics.
PMID- 27492497
TI - Gold Nanoshells: Combined Near Infrared Photothermal Therapy and Chemotherapy
Using Gold Nanoshells Coated Liposomes to Enhance Antitumor Effect (Small
30/2016).
AB - Gold nanoshell coated oleanolic acid liposomes mediating by chitosan (GNOLs), are
designed and successfully synthesized for the first time by D. Gao and co-workers
on page number 4103. An excellent near infrared (NIR) photothermal effect, pH
responsive drug controlled release and tumor targeting properties are
demonstrated. By combining NIR photothermal therapy and chemotherapy, the smart
drug delivery system exhibits a superior antitumor property in vitro and in vivo.
PMID- 27492494
TI - Novel Shank3 mutant exhibits behaviors with face validity for autism and altered
striatal and hippocampal function.
AB - Mutations/deletions in the SHANK3 gene are associated with autism spectrum
disorders and intellectual disability. Here, we present electrophysiological and
behavioral consequences in novel heterozygous and homozygous mice with a
transcriptional stop cassette inserted upstream of the PDZ domain-coding exons in
Shank3 (Shank3E13 ). Insertion of a transcriptional stop cassette prior to exon
13 leads to loss of the two higher molecular weight isoforms of Shank3.
Behaviorally, both Shank3E13 heterozygous (HET) and homozygous knockout (KO) mice
display increased repetitive grooming, deficits in social interaction tasks, and
decreased rearing. Shank3E13 KO mice also display deficits in spatial memory in
the Morris water maze task. Baseline hippocampal synaptic transmission and short
term plasticity are preserved in Shank3E13 HET and KO mice, while both HET and KO
mice exhibit impaired hippocampal long-term plasticity. Additionally, Shank3E13
HET and KO mice display impaired striatal glutamatergic synaptic transmission.
These results demonstrate for the first time in this novel Shank3 mutant that
both homozygous and heterozygous mutation of Shank3 lead to behavioral
abnormalities with face validity for autism along with widespread synaptic
dysfunction. Autism Res 2017, 10: 42-65. (c) 2016 International Society for
Autism Research, Wiley Periodicals, Inc.
PMID- 27492500
TI - Erratum to: High field magnetic resonance imaging of rodents in cardiovascular
research.
PMID- 27492501
TI - Silver Ions in Non-canonical DNA Base Pairs: Metal-Mediated Mismatch
Stabilization of 2'-Deoxyadenosine and 7-Deazapurine Derivatives with 2'
Deoxycytidine and 2'-Deoxyguanosine.
AB - Novel silver-mediated dA-dC, dA*-dC, and dA*-dG base pairs were formed in a
natural DNA double helix environment (dA* denotes 7-deaza-dA, 7-deaza-7-iodo-dA,
and 7-cyclopropyl-7-deaza-dA). 7-Deazapurine nucleosides enforce silver ion
binding and direct metal-mediated base pair formation to their Watson-Crick face.
New phosphoramidites were prepared from 7-deaza-dA, 7-deaza-7-iodo-dA, and 7
cyclopropyl-7-deaza-dA, which contain labile isobutyryl protecting groups. Solid
phase synthesis furnished oligonucleotides that contain mismatches in near
central positions. Increased thermal stabilities (higher Tm values) were observed
for oligonucleotide duplexes with non-canonical dA*-dC and dA-dC pairs in the
presence of silver ions. The stability of the silver-mediated base pairs was pH
dependent. Silver ion binding was not observed for the dA-dG mismatch but took
place when mismatches were formed between 7-deazaadenine and guanine. The
specific binding of silver ions was confirmed by stoichiometric UV titration
experiments, which proved that one silver ion is captured by one mismatch. The
stability increase of canonical DNA mismatches might have an impact on cellular
DNA repair.
PMID- 27492502
TI - Absence of premature senescence in Werner's syndrome keratinocytes.
AB - Werner's syndrome (WS) is an autosomal recessive genetic disorder caused by loss
of function mutation in wrn and is a useful model of premature in vivo ageing.
Cellular senescence is a plausible causal mechanism of mammalian ageing and, at
the cellular level, WS fibroblasts show premature senescence resulting from a
combination of telomeric attrition and replication fork stalling. Over 90% of WS
fibroblast cultures achieve <20 population doublings (PD) in vitro compared to
wild type human fibroblast cultures. It has been proposed that some cell types,
capable of proliferation, will fail to show a premature senescence phenotype in
response to wrn mutations. To test this hypothesis, human dermal keratinocytes
(derived from both WS and wild type patients) were cultured long term. WS
Keratinocytes showed a replicative lifespan in excess of 100 population doublings
but maintained functional growth arrest mechanisms based on p16 and p53. The
karyotype of the cells was superficially normal and the cultures retained markers
characteristic of keratinocyte holoclones (stem cells) including p63 expression
and telomerase activity. Accordingly we conclude that, in contrast to WS
fibroblasts, WS keratinocytes do not demonstrate slow growth rates or features of
premature senescence. These findings suggest that the epidermis is among the
tissue types that do not display symptoms of premature ageing caused by loss of
function of wrn. This is in support that Werner's syndrome is a segmental
progeroid syndrome.
PMID- 27492503
TI - Populus euphratica: an incompatible host for biotrophic pathogens?
PMID- 27492504
TI - Postpartum education and lifestyle changes for preventing type 2 diabetes in
Turkish women with previous gestational diabetes: A retrospective study.
AB - BACKGROUND: Women with previous gestational diabetes mellitus (GDM) have at least
sevenfold increased risk for developing type 2 diabetes compared with non-GDM
mothers. The risk can be decreased by self-care measures. AIM: The aim of this
study was to explore the postpartum education and lifestyle changes of Turkish
women with previous GDM. METHOD: This was a retrospective descriptive
epidemiological study. A total of 111 women who had given birth within the
previous 3-4 years were interviewed by telephone between December 2013 and April
2014. RESULTS: The 83.8% of the women with GDM had not received education related
to exercise, while 40.5% received no education regarding the importance of diet.
More importantly, while 68.5% had been informed about testing blood glucose
levels postpartum, a large majority, 69.3%, did not know for how long they would
have had to continue testing their glucose levels. However, 31.3% of those who
monitored their glucose levels had glucose intolerance. In terms of lifestyle
changes, less than half of the women, 48.6%, had made changes in their diet and
the majority, 51.4%, were inactive. CONCLUSION: Women need access to sustained
education and supportive counselling both to motivate and to minimize the risk of
type 2 diabetes after GDM.
PMID- 27492505
TI - Emodin alleviates hepatic steatosis by inhibiting sterol regulatory element
binding protein 1 activity by way of the calcium/calmodulin-dependent kinase
kinase-AMP-activated protein kinase-mechanistic target of rapamycin-p70 ribosomal
S6 kinase signaling pathway.
AB - AIM: To investigate the effects of emodin on the treatment of non-alcoholic fatty
liver and the underlying mechanisms. METHODS: In vitro, hepatocytes were treated
with 1 mM free fatty acid together with various concentrations of emodin. In
vivo, Sprague-Dawley rats were divided into a control group, high-fat diet (HFD)
group, and three HFD groups treated with 40, 80, and 160 mg/kg emodin,
respectively. After being fed a HFD for 4 weeks, rats were orally dosed with
emodin once daily for 8 weeks. The biochemical parameters and histology features
were examined. The expression of lipogenic and lipolytic gene and protein and the
phosphorylation of calcium/calmodulin-dependent kinase kinase (CaMKK), AMP
activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR) and p70
ribosomal S6 kinase (p70S6K) were measured in vitro and in vivo. RESULTS: Emodin
improved lipid accumulation in vitro and in vivo. Emodin downregulated the levels
of sterol regulatory element binding protein 1 (SREBP1) and its target enzymes
but increased lipolysis-related proteins and mRNA. Phosphorylation of AMPK was
increased, while phosphorylation of mTOR and p70S6K were suppressed by emodin.
The nuclear translocation of SREBP1 was inhibited by emodin by AMPK and mTOR.
Emodin activated AMPK by CaMKK and reversed the reduction of CaMKK in HFD-fed
rats. CONCLUSION: Emodin effectively ameliorates hepatic steatosis through the
CaMKK-AMPK-mTOR-p70S6K-SREBP1 signaling pathway.
PMID- 27492506
TI - The KT Jeang Retrovirology prize 2016: Frank Kirchhoff.
PMID- 27492507
TI - Long-term effects of azithromycin in patients with cystic fibrosis.
AB - BACKGROUND: Low-dose azithromycin has beneficial effects on severity of the lung
disease in cystic fibrosis (CF) patients for a period of 6-12 months after
initiation of the treatment. Although its impact in the longer term is uncertain,
this treatment is frequently used chronically. The aim of this retrospective
study was to investigate the effects of low-dose azithromycin treatment on the
progression of CF lung disease in patients treated for more than 12 months.
METHODS: All of the CF patients followed in our pediatric center and who had been
on low-dose azithromycin for more than 12 sequential months were included. The
clinical data were collected for one year before and three years after the
initiation of the azithromycin treatment. These data comprised lung function
analyses, rates of exacerbations and of antibiotic courses, and changes in the
airways' bacterial colonization. RESULTS: A total of 68 patients were included
(mean age: 9.95 yrs (3.61)). After 12 months, significant reductions in the
numbers of pulmonary exacerbations and antibiotic courses were present. However,
this effect was not maintained in the subsequent periods, during which increased
rates of both pulmonary exacerbations and antibiotic courses were observed. The
lung function decline was not modified during the treatment, and a decreasing
time-dependent trend typical of CF was observed for the various parameters. No
differences in the airway colonization by pathogens such as Pseudomonas
aeruginosa and methicillin-sensitive and/or -resistant Staphyloccocus aureus were
observed during the treatment. However, isolated Staphyloccocus aureus strains
became resistant to macrolides after 6 months of azithromycin and remained
resistant thereafter. CONCLUSIONS: No clinical benefits of low-doses azithromycin
were present after one year of treatment in young CF patients. Selection for
macrolide-resistant strains of bacteria occurred, which should lead to a
reconsideration of the duration of azithromycin treatment in CF.
PMID- 27492508
TI - Comparison of ventilator-integrated end-tidal CO2 and transcutaneous CO2
monitoring in home-ventilated neuromuscular patients.
AB - BACKGROUND: Non-invasive transcutaneous capnometry (TcCO2) is used to assess the
home ventilation's efficiency. Recently, end-tidal CO2 (ETCO2) sensors have been
integrated in life-support home ventilators. The purpose of this study was to
compare the ventilator-integrated ETCO2 with TcCO2, in home-ventilated
neuromuscular disease patients. METHODS: ETCO2 and TcCO2 were simultaneously
measured during one night in 28 patients. Daytime blood gases were drawn on the
following morning to measure arterial PCO2 (PaCO2). RESULTS: Compared to PaCO2
values, both ETCO2 and TcCO2 showed a small bias (-0.1 mmHg and 0.6 mmHg,
respectively) and a similar critical difference (6.8 mmHg and 7.3 mmHg,
respectively). We found a good correlation between ETCO2 and TcCO2, both
considering the mean nocturnal PCO2 (r = 0.897, p < 0.001; bias -1.1 [- 9.0; 6.9]
mmHg) and the maximal PCO2 value over the night (r = 0.905, p < 0.001; bias 3.1 [
4.5; 10.8] mmHg). The concordance of the two techniques in detecting overnight
PCO2 fluctuations was high, with r = 0.919 (p < 0.001) for the time spent with
PCO2 >45 mmHg and r = 0.943 (p < 0.001) for the time with PCO2 >50 mmHg.
CONCLUSIONS: The ventilator-integrated end-tidal CO2 monitoring is as reliable as
the currently used transcutaneous measurement, resulting to be a valuable proxy
of the overnight PCO2 evolution. This result opens the possibility of a
simplification in the monitoring of home ventilated patients, since ETCO2
measurement can be performed directly at home, with a low additional cost.
However, the accuracy of both these measurement techniques is not sufficient to
replace blood gases, which remain the reference examination. ClinicalTrials.gov
registration:NCT02068911.
PMID- 27492509
TI - Combined pulmonary fibrosis and emphysema: The many aspects of a cohabitation
contract.
AB - Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity
characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis.
Patients with this condition experience severe dyspnea and impaired gas exchange
with preserved lung volumes. The diagnosis of the CPFE syndrome is based on HRCT
imaging, showing the coexistence of emphysema and pulmonary fibrosis both in
varying extent and locations within the lung parenchyma. Individual genetic
background seem to predispose to the development of the disease. The risk of the
development of pulmonary hypertension in patients with CPFE is high and related
to poor prognosis. CPFE patients also present a high risk of lung cancer.
Mortality is significant in patients with CPFE and median survival is reported
between 2.1 and 8.5 years. Currently, no specific recommendations are available
regarding the management of patients with CPFE. In this review we provide
information on the existing knowledge on CPFE regarding the pathophysiology,
clinical manifestations, imaging, complications, possible therapeutic
interventions and prognosis of the disease.
PMID- 27492510
TI - Angiopoietin-2 expression in patients with an acute exacerbation of idiopathic
interstitial pneumonias.
AB - BACKGROUND AND OBJECTIVE: We hypothesized that increased pulmonary vascular
permeability may play a role in the pathogenesis of an acute exacerbation of the
idiopathic interstitial pneumonias (AE-IIPs). Angiopoietin-2 (Ang-2) promotes
endothelial activation, destabilization, and inflammation. The purpose of this
study was to examine whether Ang-2 expression was associated with the
pathogenesis of AE-IIPs. METHODS: Twenty-three patients with AE-IIP patients, 18
acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, 37
idiopathic pulmonary fibrosis (IPF) patients, and 33 healthy volunteers (HVs)
were enrolled. The serum level of Ang-2 was measured by an enzyme-linked
immunosorbent assay. RESULTS: The serum levels of Ang-2 were higher in AE-IIPs
and ALI/ARDS patients than in IPF patients and HVs; the BALF levels of Ang-2 were
also higher than in IPF patients. There was a positive correlation between the
serum level of Ang-2 and the CRP in patients with AE-IIP patients, whereas a
significant positive correlation was found between the serum Ang-2 level and the
CRP or SOFA scores of the ALI/ARDS patients. Although the baseline Ang-2 level
was not related to survival, the Ang-2 levels significantly declined in survivors
during treatment, while they did not change in non-survivors. CONCLUSIONS:
Increased pulmonary vascular permeability and inflammation due to Ang-2 may play
a role in the pathogenesis of AE-IIPs.
PMID- 27492511
TI - Frequency of comorbidities in chronic obstructive pulmonary disease, and impact
on all-cause mortality: A population-based cohort study.
AB - BACKGROUND: In chronic obstructive pulmonary disease (COPD), the role of specific
comorbidities on all-cause mortality is of major interest particularly with a
database representative of the beneficiaries covered by the French health system.
We investigated the frequency and the role of major comorbidities on all-cause
mortality in a population-based cohort of COPD patients, and whether this impact
was modulated by gender. METHODS: A historical cohort was identified in the
French claims data. Patients aged >=45 years were selected in 2006 from the
French national claims data (1/97(th) random sample) by at least one of the
following criteria: (a) COPD-related hospitalisations, (b) long-term disease
status for COPD, (c) dispensations of bronchodilators. Cardiovascular diseases,
diabetes, depression and cancer were defined by specific therapy and/or long-term
disease status. The impact of comorbidities on mortality was investigated during
a seven-year follow-up period (2007-2013), using Cox models. RESULTS: In 4,237
patients (mean age 68 years, 55% males, mean annual death-rate 4.9%),
cardiovascular diseases, diabetes, depression and cancers were identified in
68.7%, 15.2%, 14.2% and 10.6% of patients, respectively. Associations with
mortality were significant for cardiovascular diseases (HR = 1.2, 95%CI = [1.0
1.4]), diabetes (HR = 1.2, 95%CI = [1.0-1.4]), depression (HR = 1.4, 95%CI = [1.2
1.6]) and cancers (HR = 1.6, 95%CI = [1.4-1.9]), with no difference between
genders. CONCLUSIONS: In the French population, major comorbidities are common in
COPD, particularly cardiovascular diseases that occur in over two thirds of
patients. The impact of comorbidities on mortality was not related to their
prevalence, with cancer having the largest impact.
PMID- 27492512
TI - Nonspecific interstitial pneumonia preceding diagnosis of collagen vascular
disease.
AB - BACKGROUND: The aim of this study was to evaluate the incidence and clinical
features of patients who developed collagen vascular disease (CVD) after an
initial diagnosis of idiopathic nonspecific interstitial pneumonia (NSIP).
METHODS: We conducted a retrospective review of 72 consecutive patients with NSIP
who were diagnosed by surgical lung biopsy in our institution (idiopathic NSIP, n
= 35; CVD-NSIP, n = 37 at initial diagnosis). No patients fulfilled the American
College of Rheumatology criteria for a diagnosis with CVD within six months after
the diagnosis of idiopathic NSIP. RESULTS: Of 35 patients initially diagnosed
with idiopathic NSIP, six patients (17.1%) developed CVD during the follow-up
period (5.5 +/- 5.0 years); three patients were diagnosed with dermatomyositis
(DM), two patients with overlap syndrome (DM and Sjogren's syndrome), and one
patient with rheumatoid arthritis. The mean time until CVD diagnosis was 2.0
years (six months - 3.5 years), and the one-, two- and three-year incidences of
CVD development were 3.6%, 15.2% and 20.0%, respectively. There was no
significant difference in clinical characteristics and survival among patients
with NSIP preceding CVD diagnosis, those with idiopathic NSIP, or those with CVD
NSIP. In addition, at the time of initial diagnosis, there was no significant
difference for the fulfillment of previous criteria such as interstitial
pneumonia with autoimmune feature (IPAF) between patients with NSIP preceding CVD
diagnosis and those with idiopathic NSIP. CONCLUSIONS: It is difficult to predict
CVD occurrence and careful attention is needed to detect the development of CVD
in patients with idiopathic NSIP.
PMID- 27492513
TI - Diagnostic value of (1 -> 3)-beta-D-glucan in bronchoalveolar lavage fluid for
invasive fungal disease: A meta-analysis.
AB - BACKGROUND: The serum (1 -> 3)-beta-D-glucan (BG) assay has been approved for
diagnosing invasive fungal diseases (IFDs). However, the performance of (1 -> 3)
beta-D-glucan assay in bronchoalveolar lavage (BAL) fluid is various among
studies. The present study aimed to assess the accuracy of (1 -> 3)-beta-D-glucan
assay in bronchoalveolar lavage fluid for the diagnosis of invasive fungal
diseases by means of meta-analysis and systematic review of relevant studies.
METHOD: The sensitivity, specificity, positive likelihood ratio (PLR), negative
likelihood ratio (NLR), diagnostic odds ratio (OR) and a summary receiver
operating characteristic curve of BAL-BG for diagnosing invasive fungal diseases
were pooled using meta-analysis. We also performed meta-regression analysis.
RESULTS: A total of 838 patients (138 with proven or probable invasive fungal
diseases), included in 6 studies, were analyzed. The pooled sensitivity,
specificity, PLR, NLR and diagnostic odds ratio were 0.52 (95%CI, 0.38-0.53),
0.58 (95%CI, 0.55-0.61), 1.34 (95%CI, 1.08-1.66), 0.82 (95% CI, 0.63-1.07) and
1.71 (95%CI, 1.01-2.92) respectively. The area under the summary receiver
operating characteristic curve, with 95% confidence intervals was 0.61 (95%CI,
0.67-0.55). CONCLUSION: The accuracy of (1 -> 3)-beta-D-glucan test in
bronchoalveolar lavage fluid is marginal, so that the results should not be
interpreted alone but can be used as a part of full assessment with clinical
features, image findings and other laboratory results for the diagnosis of
invasive fungal diseases.
PMID- 27492514
TI - Swallowing function and chronic respiratory diseases: Systematic review.
AB - BACKGROUND: The precise coordination between breathing and swallowing is an
important mechanism to prevent pulmonary aspiration. Factors that alter breathing
patterns and ventilation, such as chronic respiratory diseases, may influence
that precise coordination of breathing and swallowing. PURPOSE: The purpose of
this systematic literature review is to examine the effects of chronic
respiratory diseases on swallowing function. METHOD: Literature searches were
performed using the electronic databases PubMed and Embase. All articles meeting
the eligibility criteria up to March 2016 were included. RESULTS: All articles
included studied Chronic Obstructive Pulmonary Diseases (COPD) or Obstructive
Sleep Apnea (OSA); no studies involving other respiratory diseases were found. A
total of 1069 abstracts were retrieved, of which twenty-six studies met the
inclusion criteria; eleven studies dealt with OSA and fifteen studies dealt with
COPD. CONCLUSION: The outcome data indicate that chronic respiratory diseases
increase the prevalence of oropharyngeal dysphagia (OD) in patients. However, the
relative small number of studies, differences in selection criteria, definitions
and assessment techniques used for diagnosing OSA, COPD, and OD point to the need
for further research.
PMID- 27492516
TI - Perioperative respiratory care in obese patients undergoing bariatric surgery:
Implications for clinical practice.
AB - Obesity is an increasing problem worldwide. The number of people with obesity
doubled since the 1980's to affect an estimated 671 million people worldwide.
Obese patients in general have an altered respiratory physiology and can have an
impaired lung function, which leads to an increased risk of developing pulmonary
complications during anaesthesia and after bariatric surgery (approximately 8%).
Therefore the respiratory management of the bariatric surgical patient provides a
number of challenges. This review will focus on the perioperative respiratory
care in bariatric surgical patients discussing respiratory physiology in the
obese and perioperative respiratory care in bariatric surgery. Finally the value
of preoperative pulmonary function testing and preoperative OSAS screening will
be discussed.
PMID- 27492515
TI - Non-invasive screening for pulmonary hypertension in idiopathic pulmonary
fibrosis.
AB - BACKGROUND: Pulmonary hypertension (PH) is a common complication of idiopathic
pulmonary fibrosis (IPF) that is associated with poor prognosis. Noninvasive
screening for PH in IPF patients is challenging and a combination of several
noninvasive determinations can improve discrimination. METHODS: We included 235
IPF patients who underwent right heart catheterization (RHC) as part of the lung
transplant evaluation. We measured electrocardiographic (ECG) and
echocardiographic variables as well as the pulmonary artery (PA) and ascending
aorta (AA) diameters on chest CT. We recorded results of arterial blood gases
(ABG), pulmonary function (PFT) and 6-min walk tests (6MWT). RESULTS: Several
variables were predictors of PH in IPF patients in univariable models including a
lower arterial oxygenation and 6MWT distance; worse right ventricular (RV)
function, rightward deviation of the QRS axis and a higher FVC/DLCOc ratio, PA/AA
diameter ratio, and estimated RV systolic pressure. In multivariable analysis, a
worse RV function and higher PA/AA ratio remained predictors of PH (c-index 0.75
(0.65-0.84)). Similarly, a worse RV function, a higher PA/AA ratio and a
rightward QRS axis deviation were independent predictors of precapillary PH (c
index 0.86 (0.76-0.92)). A combination of PA/AA diameter ratio <1.1, a QRS axis
<90 degrees and normal RV function showed a negative predictive value of 85% for
precapillary PH. CONCLUSIONS: There are significant differences in ECG,
echocardiographic, chest CT, PFT and ABG parameters between IPF patients with and
without PH. However, these noninvasive tests alone or combination have limited
discrimination ability for PH screening in IPF.
PMID- 27492517
TI - Undernutrition state in patients with chronic obstructive pulmonary disease. A
critical appraisal on diagnostics and treatment.
AB - 'Undernutrition state' (UNS) is an ominous condition, in particular when
associated with chronic obstructive pulmonary disease (COPD). In this review we
discuss pathophysiological mechanisms and how UNS is defined and diagnosed. It
seems unlikely that COPD-patients with established UNS have similar potential of
reversibility (treatability) upon nutrition interventions as patients at a risk
of developing such a condition, i.e. patients with low energy/nutrient intake,
since pathophysiological, biochemical and metabolic conditions may differ
substantially. We summarize the results of 7 of 17 published randomized
controlled trials of nutritional supplementation in COPD-patients with defined
UNS in the latest Cochrane review (2012). We thus excluded 10 of 17 trials
included in review (2012), mostly because those studies also included patients
with 'risk of' UNS. The seven included trials exhibit extensive heterogeneity for
all studied variables. Most studies did not show beneficial effects of
nutritional supplementation, although some reported minor increase in body weight
and physical function of unclear clinical relevance. In contrast to the Cochrane
review we conclude that it is difficult to draw firm conclusions regarding the
effect of nutritional supplements in patients with COPD and UNS. Improved
knowledge in this area is of utmost importance and some factors which should be
considered in future studies are suggested.
PMID- 27492518
TI - Clinical characteristics of adult asthma associated with small airway
dysfunction.
AB - Suboptimal asthma control is common despite modern asthma therapy. The degree of
peripheral airway involvement remains unclear and poor medication delivery to
these regions might be a contributing reason for this failure in obtaining
adequate symptom control. A cohort of 196 adults (median (range) age 44 (18-61)
years, 109 females, 54 ex-smokers, six current smokers) with physician-diagnosed
asthma were recruited from primary care. Subjects were characterized clinically
by interviews, questionnaires, skin prick tests (SPT) and blood eosinophil
counts. Lung function was assessed by spirometry, impulse oscillometry (IOS) and
nitrogen multiple breath washout (N2 MBW). IOS assessed peripheral airway
resistance (FDR, frequency dependence of resistance). N2 MBW assessed global
ventilation inhomogeneity (LCI, lung clearance index), specific indices of
peripheral airway function (Scond * VT and Sacin * VT; VT, tidal volume), and
inter-regional inhomogeneity (specific ventilation ratio). Never-smoking healthy
cohorts of 158 and 400 adult subjects provided local reference values for IOS and
N2 MBW variables, respectively. Peripheral airway dysfunction was detected in 31%
(FDR or specific ventilation ratio) to 47% (Scond x VT) of subjects. Risk factors
for peripheral airway dysfunction were identified. Among subjects with low FEV1
and either positive smoking history and/or blood eosinophilia (>4.0%), 63% had
abnormality across all peripheral airway outcomes, whilst only one subject was
completely normal. Abnormal peripheral airway function was present in a large
proportion of adult asthmatics at baseline. Reduced FEV1, a positive smoking
history, and/or blood eosinophilia identified "a small airway asthma subtype"
that might benefit from peripheral airway targeted therapy.
PMID- 27492519
TI - Observational study of lung transplant recipients surviving 20 years.
AB - BACKGROUND: Lung transplant recipients have reduced long-term survival compared
with other solid organ recipients. There is a lack of published data on the
characteristics of very long term survivors. METHODS: We describe the
demographics, clinical history and post-procedure function of all lung transplant
recipients who have survived greater than 20 years at our centre. RESULTS: At the
time of analysis there were 21 (16.4%) of 128 patients who survived over 20
years. The mean age at transplantation was 31.8 +/- 9.9 years. Five of 21 had
undergone single-lung, eight double-lung and eight heart-lung transplant
procedures. At the last evaluation, mean percentage predicted FEV1 in recipients
of single and double lung were 51.3% and 57.9% respectively. By 20 years, 19
(90.5%) patients had developed bronchiolitis obliterans syndrome (BOS) with three
(14%) BOS 1, six (29%) BOS 2 and 10 (48%) BOS 3 and two (9.5%) free from BOS. The
median time to onset of BOS was 9.7 years (range 1.6-17.9). Of eight patients
(38%) who required renal replacement, four (19%) had successfully undergone renal
transplantation and four (19%) were on haemodialysis. Only one patient (5%) had
symptomatic osteoporosis. Nineteen patients (90%) were treated for hypertension.
Five patients (24%) had diabetes, all with an underlying diagnosis of cystic
fibrosis and four of them developing diabetes post operatively. CONCLUSIONS: In
our experience, 20-year survivors of lung transplantation had a delayed onset of
BOS and morbidities due to immunosuppression that can be appropriately managed
leading to long-term survival.
PMID- 27492520
TI - Stepping down from combination asthma therapy: The predictors of outcome.
AB - BACKGROUND: Stepping down from combination asthma therapy (inhaled
corticosteroids (ICS) + long-acting beta2 agonists (LABA)) is often avoided due
to fear of exacerbations, which may lead to overmedication in well-controlled
asthma. A better knowledge about the predictors of outcome might encourage
clinicians to start stepping down more often than previously. METHODS: In 55
subjects with well controlled asthma and combination therapy, LABAs were
discontinued first, followed by ICS dose halving, and then cessation, in six
weeks' intervals. The ability of Juniper's asthma control questionnaire (ACQ),
ambulatory peak flow monitoring, spirometry, and hypertonic saline challenge to
predict the outcomes of medication reductions were assessed. RESULTS: The
proportions of subjects experiencing an exacerbation at each step were: 4 out of
55 subjects (7%) after LABA cessation, 4 out of 25 subjects (16%) after ICS dose
halving, and 21 out of 46 subjects (46%) after ICS cessation. All exacerbations
could be managed on an outpatient basis. There were 126 step-downs altogether.
ACQ score < 0.29 (likelihood ratio 2.30 (1.05-5.05)), ACQ without spirometry <
0.15 (2.17 (0.96-4.90)) and FEV1 > 96% of predicted (2.18 (1.03-4.61)) predicted
a successful outcome after step-down. Cough responsiveness to saline,
bronchoconstrictive responsiveness to saline, and peak flow variation were not
associated with the outcome. CONCLUSION: Combination therapy can often be reduced
in controlled asthma but total cessation of ICSs must be carefully considered.
Simple investigations, namely asthma control assessment by validated
questionnaire and spirometry, help to predict the outcome of stepping down. TRIAL
REGISTRY: The study was registered in ClinicalTrials.gov database
(https://clinicaltrials.gov, KUH5801124).
PMID- 27492521
TI - Improvement of physical activity after endobronchial valve treatment in emphysema
patients.
AB - RATIONALE: Bronchoscopic lung volume reduction using endobronchial valves is a
promising treatment for severe emphysema patients without collateral ventilation.
Physical activity is an important contributing factor for the autonomy, morbidity
and mortality of these patients. OBJECTIVE: We investigated the impact of
endobronchial valve treatment on physical activity in severe emphysema patients.
METHODS: Physical activity was measured for 7 days by a triaxial accelerometer at
baseline and 6 months follow-up after EBV treatment, and compared with standard
medical care in a randomized controlled trial. RESULTS: Forty-three patients
(77%female, age 59 +/- 9years, FEV1 30 +/- 7%pred, steps 3563 +/- 2213per/day)
wore the accelerometer and were included in the analysis. Nineteen patients
received EBV treatment and 24 standard medical care. At baseline, physical
activity level was comparable between groups. After 6 months, the endobronchial
valve group significantly improved compared to the controls in steps/day (+1252vs
148) and locomotion time (+17vs-2 min/day). Change in sit duration (0vs + 27
min/day) did not significantly differ. CONCLUSIONS: Physical activity
significantly improved after endobronchial valve treatment in severe emphysema
patients. This improvement was without any specific encouragement on physical
activity. CLINICAL TRIAL NUMBER: Dutch trial register: NTR2876.
PMID- 27492522
TI - Activity limitation and exertional dyspnea in adult asthmatic patients: What do
we know?
AB - Limitation of activity is the most cited symptom described by uncontrolled asthma
patients. Assessment of activity limitation can be undertaken through several
ways, more or less complex, subjective or objective. Yet little is known about
the link between patients sensations and objective measurements. The present
review reports the current knowledge regarding activity limitation and symptom
perception (i.e., exertional dyspnea) in adult patients with asthma. This work is
based on references indexed by PubMed, irrespective of the year of publication.
Overall, patients with stable asthma do not have a more sedentary lifestyle than
healthy subjects. However, during a cycle ergometric test, the maximal load is
reduced when FEV1, FVC and muscle strengths are decreased. Additionally, during
the six-minute walking test, mild asthma patients walk less than healthy subjects
even if the minimal clinically important difference is not reached. The major
complaint of asthma patients when exercising is dyspnea that is mainly related to
the inspiratory effort and also to dynamic hyperinflation in some circumstances.
Finally, the administration of bronchodilator does not improve the ventilatory
pattern and the exercise capacity of asthma patients and little is known on its
effect on exertional dyspnea. The present review allows to conclude that until
now there is no gold standard test allowing the objective assessment of "activity
limitation and exertional dyspnea" in asthma patients.
PMID- 27492523
TI - Comparison of endobronchial ultrasound and high resolution computed tomography as
tools for airway wall imaging in asthma and chronic obstructive pulmonary
disease.
AB - INTRODUCTION: Airway remodeling in asthma and chronic obstructive pulmonary
disease (COPD) results in bronchial wall thickening. Bronchial wall thickness
(BWT) can be assessed in high-resolution computed tomography (HRCT) and
endobronchial ultrasound (EBUS). AIMS: To compare BWT measured by EBUS and HRCT
in patients with mild-to-moderate asthma and COPD, and to evaluate the
relationship between the BWT and pulmonary function. METHODS: The study included
patients with mild-to-moderate asthma (n = 24), COPD (n = 36) and controls (n =
12). Bronchoscopy with EBUS (radial probe) and HRCT were performed to measure the
BWT in the segmental bronchus. RESULTS: Good overall agreement between EBUS and
HRCT measurements of BWT was demonstrated. Median HRCT-BWT did not reveal any
significant differences between individuals with asthma and COPD, and control
subjects: 1.56 (1.27-1.70) mm, 1.62 (1.45-1.90) mm, and 1.63 (1.41-1.77) mm,
respectively (p = 0.315). In contrast, median BWT measured by EBUS was
significantly higher in asthma and COPD groups when compared to controls: 1.20
(1.02-1.41) mm, 1.19 (1.10-1.48) mm, and 0.99 (0.90-1.08) mm, respectively (p =
0.006). There were no differences in BWT in mild-to-moderate asthma and COPD or
significant correlations between BWT and the results of pulmonary function tests.
CONCLUSIONS: The use of EBUS to assess BWT in asthma and COPD is feasible and it
shows good compatibility with HRCT. A tendency towards lower BWT values in EBUS
when compared to HRCT was observed. The finding that EBUS measurements
demonstrated the differences between BWT in patients with obstructive lung
diseases and controls, may suggest that EBUS is a more sensitive method to study
the BWT than HRCT.
PMID- 27492524
TI - Novel variants of SERPIN1A gene: Interplay between alpha1-antitrypsin deficiency
and chronic obstructive pulmonary disease.
AB - Alpha1-antitrypsin (AAT) is one of the major circulating anti-protease whose
levels in circulation are raised during excessive amount of proteases, especially
neutrophil elastase (NE) released during the course of inflammation. Proteolytic
attack of NE on peripheral organs, more exclusively on lung parenchyma has severe
consequence that may precipitate pulmonary emphysema. Normally, human body has
its own molecular and physiological mechanisms to synthesize and regulate the
production of anti-protease like AAT to mitigate the extent of inflammatory
damage. AAT coded by serine-protease inhibitor (SERPINA1) is predominantly
expressed in hepatocytes and to some extent by macrophages, monocytes, lung
tissue etc. The observation that persons with AAT deficiency developed chronic
obstructive pulmonary disease (COPD) and early-onset of emphysema proposed a role
for pathways connecting AAT in pathogenesis. Extensive studies have been done
till now to bridge a connection between numerous genetic polymorphisms of
SERPINA1 gene and the early onset of COPD. Here in this review, we have
comprehensively discussed some of the variants of SERPINA1 gene discovered till
date and their association with the exacerbation of obstructive pulmonary
disease.
PMID- 27492525
TI - Can bronchial asthma with an highly prevalent airway (and systemic) vagal tone be
considered an independent asthma phenotype? Possible role of anticholinergics.
AB - Recently, we studied occurrence and role of non-respiratory symptoms (n-RSs)
before a worsening of asthma symptoms. Some n-RSs such as anxiety, reflux,
heartburn, abdominal pain, which appeared within 3 h before the onset of an
asthma attack, are the likely result of an imbalance between
sympathetic/parasympathetic systems with an increase in cholinergic tone.
Therefore, it is likely that some of these n-RSs induced by the increased
cholinergic tone might be present related with specific parasympathetic
associated respiratory symptoms such as those elicited by airway narrowing. It is
likely that, at least in some categories of asthmatics, an increased cholinergic
tone, rather than other well-known factors, might play a prevalent role in
triggering bronchospasm. If this is the case, it is possible to speculate that
the use of anticholinergic agents (mainly those with long-acting activity) in
patients suffering from asthma should be more beneficial in individuals
characterized by a higher degree of cholinergic tone that, consequently might be
the ideal target for the use of long-acting anticholinergics and, possibly,
represent a novel asthma phenotype. The presence of parasympathetic-associated n
RSs might help the physician to identify this type of patients, although this
might be followed by a more detailed assessment.
PMID- 27492526
TI - Prevalence of depression in COPD: A systematic review and meta-analysis of
controlled studies.
AB - BACKGROUND: Depression is frequently reported in association with COPD. However,
the prevalence of depression in these patients ranges largely. This study aimed
to systematically review the prevalence of depression in COPD and controls and to
explore remaining causes of inter-study variability in the reported prevalence.
METHODS: A systemic review of the literature and a meta-analysis was performed to
evaluate the source of variability in the reported rates of depression in stable
COPD. Main eligibility criteria were: controlled studies with a sample size >100,
outpatients with COPD diagnosed by spirometry and, use of a validated depression
screening instrument. RESULTS: From 1613 studies identified, eight controlled
studies were included in the review. The number of participants in the pooled
studies was of 5.552 COPD subjects and 5.211 controls. Using stricter criteria
for study selection reduced the variability of the depression prevalence in COPD
and controls, which was 27.1% [25.9-28.3] in COPD subjects and 10.0% [9.2-10.8]
in the control group. The pooled odds ratio and 95% CI was 3.74 [2.4-5.9].
However, the heterogeneity across studies was high. Possible explanatory factor
included sample sizes, COPD/controls ratio, smoker's/nonsmokers ratio and
qualitative differences (source of subjects, instruments to screen depression,
COPD severity, smoking status, and comorbidities). CONCLUSION: The study
highlights the variability in estimates of depression prevalence in COPD. It
could be explained by methodological differences across the included studies.
This suggests that a standardization is critical to improve precision of the
estimates.
PMID- 27492527
TI - The barriers to accessing primary care resulting in hospital presentation for
exacerbation of asthma or chronic obstructive pulmonary disease in a large
teaching hospital in London.
AB - Asthma and chronic obstructive pulmonary disease (COPD) account direct costs of
L1 billion each per year in the United Kingdom (UK). A national review of asthma
deaths found that a significant proportion of patients die without seeking
medical assistance or before emergency medical care could be provided. This study
aims to establish the pathway that patients undertake to access care in the lead
up to an accident and emergency (A&E) attendance and/or inpatient admission.
Patients attending A&E and/or following an inpatient admission due to an
exacerbation of asthma or COPD were reviewed by a specialist respiratory
pharmacist during weekday working hours. Over a one-year period, 920 (224 asthma
and 696 COPD) presentations for exacerbation of asthma and COPD were reviewed.
Although the majority of the patients were registered with a general practitioner
(GP), less than 50% received medical attention from their GP and/or had an active
intervention prior to presenting to hospital. These findings correlate with those
found in the national review of asthma deaths. At a time of increasing demands on
healthcare resources, these results pose the question of how we can better triage
patients to appropriate care settings to minimise unscheduled care and improve
patient outcomes.
PMID- 27492528
TI - Profile of difficult to treat asthma patients referred for systematic assessment.
AB - AIM: We determined the proportion of asthma patients under specialist care who
remain difficult-to-treat and might benefit from systematic assessment. We
additionally report the characteristics and indications for referral in 90
patients who received systematic assessment for difficult asthma. METHODS: We
conducted a three-month prospective audit of our hospital's general asthma
clinic. We then analyzed consecutive patients over 18 months referred on for
systematic assessment of difficult asthma. RESULTS: Over 3 months, 22/166
patients (13.3%) in the general asthma clinic were considered likely to benefit
from systematic assessment of difficult asthma. These patients had higher inhaled
steroid requirements (890 +/- 604 mg), lower lung function (FEV1: 65 +/- 18%),
and more often received GINA step 5 treatment (22.7%). However, 7/22 (32%) of
suitable patients were not referred for assessment, mainly due to patient
factors. Over 18 months, 90 patients received systematic assessment for difficult
asthma, on account of poor symptom control (62%), frequent exacerbations (44%),
poor lung function (42%), patient factors (29%), and diagnostic uncertainty
(26%). There was a high disease burden with a mean (+/-SD) asthma control test
score and asthma quality of life questionnaire score of 14 +/- 5 and 4.26 +/-
1.45 respectively. 80% fulfilled criteria for severe asthma. The majority were
either atopic (66.7%) or eosinophilic (54.4%); only 15.6% were neither. Patients
had a median of three extra-pulmonary comorbidities, of which most were
previously unrecognised. CONCLUSION: One-in-eight asthma patients already under
specialist care were suitable for systematic assessment of difficult asthma, but
a third of these were not referred due to patient factors. Diagnostic uncertainty
and patient factors were important indications for systematic assessment. Most
patients who underwent systematic assessment exhibited severe asthma phenotypes
potentially responsive to targeted treatment, but also had multiple
comorbidities. Our results highlight the importance of management strategies to
address patient factors, severe asthma biology, and concurrent contributory
conditions.
PMID- 27492529
TI - Management of obese patients with respiratory failure - A practical approach to a
health care issue of increasing significance.
AB - In the general population, prevalence of obesity is increasing continuously.
Concomitantly, a growing number of obese patients with severe illnesses presents
at intensive care units (ICU). Particularly respiratory management of this
patient group poses a challenge to intensive care physicians because of
differences in respiratory anatomy and physiology in obese compared to non-obese
individuals. Aim of this review is to present treatment options for critically
ill obese patients requiring mechanical ventilation based on current studies
concerning patient positioning, ventilatory regimen as well as extended therapy
with veno-venous extracorporeal membrane oxygenation (ECMO). The ideal concept
for respiratory management depends on multiple aspects and has to be determined
individually. Knowledge of altered respiratory anatomy and physiology in obese
patients and possible treatment options may facilitate respiratory management in
this patient group.
PMID- 27492530
TI - Challenges in managing Pseudomonas aeruginosa in non-cystic fibrosis
bronchiectasis.
AB - BACKGROUND: An Expert Forum was held at the 2014 European Respiratory Society
International Congress to address issues involved in the management of
Pseudomonas aeruginosa infection in patients with non-cystic fibrosis
bronchiectasis (NCFB). Multiple studies have found that chronic P. aeruginosa
infection is associated with more severe disease and higher morbidity and
mortality. OVERVIEW: Participants discussed appropriate management of P.
aeruginosa infection at three stages: 1) first isolation, including eradication
protocols; 2) during exacerbations; and 3) during chronic infection, including
long-term antibiotic therapy to reduce the severity of symptoms and frequency of
exacerbations. Topics covered included frequency of sputum cultures, antibiotic
treatment at first isolation and for exacerbations, optimal use of inhaled
antibiotics, indications for long-term therapy, and treatment regimens that may
reduce the frequency or severity of symptoms. Electronic polling and roundtable
discussions followed by expert insights were used to address these topics.
Significant diversity in management practices was reported among different
countries and centres, and in many cases clinical management was at variance with
published guidelines. CONCLUSIONS: This Expert Forum identified standardised
terminology, clinician training, additional research into management strategies,
and the development of new drugs as areas requiring improvement for the optimal
management of P. aeruginosa in NCFB.
PMID- 27492531
TI - The effect of N-acetylcysteine on biofilms: Implications for the treatment of
respiratory tract infections.
AB - OBJECTIVES: In airway infections, biofilm formation has been demonstrated to be
responsible for both acute and chronic events, and constitutes a genuine
challenge in clinical practice. Difficulty in eradicating biofilms with systemic
antibiotics has led clinicians to consider the possible role of non-antibiotic
therapy. The aim of this review is to examine current evidence for the use of N
acetylcysteine (NAC) in the treatment of biofilm-related respiratory infections.
METHODS: Electronic searches of PUBMED up to September 2015 were conducted,
searching for 'biofilm', 'respiratory tract infection', 'N-acetylcysteine',
'cystic fibrosis', 'COPD', 'bronchiectasis', 'otitis', and 'bronchitis' in titles
and abstracts. Studies included for review were primarily in English, but a few
in Italian were also selected. RESULTS: Biofilm formation may be involved in many
infections, including ventilator-associated pneumonia, cystic fibrosis,
bronchiectasis, bronchitis, and upper respiratory airway infections. Many in
vitro studies have demonstrated that NAC is effective in inhibiting biofilm
formation, disrupting preformed biofilms (both initial and mature), and reducing
bacterial viability in biofilms. There are fewer clinical studies on the use of
NAC in disruption of biofilm formation, although there is some evidence that NAC
alone or in combination with antibiotics can decrease the risk of exacerbations
of chronic bronchitis, chronic obstructive pulmonary disease, and rhinosinusitis.
However, the usefulness of NAC in the treatment of cystic fibrosis and
bronchiectasis is still matter of debate. Most of the studies published to date
have used oral or intramuscular NAC formulations. CONCLUSIONS: Evidence from in
vitro studies indicates that NAC has good antibacterial properties and the
ability to interfere with biofilm formation and disrupt biofilms. Results from
clinical studies have provided some encouraging findings that need to be
confirmed and expanded using other routes of administration of NAC such as
inhalation.
PMID- 27492532
TI - Tiotropium improves lung function, exacerbation rate, and asthma control,
independent of baseline characteristics including age, degree of airway
obstruction, and allergic status.
AB - BACKGROUND: Many patients with asthma remain symptomatic despite treatment with
inhaled corticosteroids (ICS) with or without long-acting beta2-agonists (LABAs).
Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and
reduce exacerbation risk in patients with symptomatic asthma. OBJECTIVE: To
determine whether the efficacy of tiotropium add-on therapy is dependent on
patients' baseline characteristics. METHODS: Two randomized, double-blind,
parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily
tiotropium Respimat((r)) 5 MUg add-on to ICS plus a LABA were performed in
parallel in patients with severe symptomatic asthma. Exploratory subgroup
analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, time to
first severe exacerbation, time to first episode of asthma worsening, and seven
question Asthma Control Questionnaire responder rate were performed to determine
whether results were influenced by baseline characteristics. RESULTS: 912
patients were randomized: 456 received tiotropium and 456 received placebo.
Tiotropium improved lung function, reduced the risk of asthma exacerbations and
asthma worsening, and improved asthma symptom control, compared with placebo,
independent of baseline characteristics including gender, age, body mass index,
disease duration, age at asthma onset, and FEV1 % predicted at screening and
reversibility. CONCLUSION: Once-daily tiotropium 5 MUg compared with placebo
improved lung function, reduced the risk of asthma exacerbations and asthma
worsening, and improved asthma symptom control, independent of a broad range of
baseline characteristics, as add-on to ICS plus LABAs in patients with severe
symptomatic asthma. TRIAL REGISTRY: ClinicalTrials.gov; numbers NCT00772538 and
NCT00776984 URL: www.clinicaltrials.gov.
PMID- 27492533
TI - Relationships between emphysema and airways metrics at High-Resolution Computed
Tomography (HRCT) and ventilatory response to exercise in mild to moderate COPD
patients.
AB - BACKGROUND AND PURPOSE: In Chronic Obstructive Pulmonary Disease (COPD) patients,
the opportunity to carry out a thoracic high-resolution CT (HRCT) scan and to
perform an incremental cardiopulmonary exercise test (CPET) increases the
possibility to identify the different clinical features of disease. The aim of
our study was to evaluate the relationships between HRCT metrics (on emphysema by
low attenuation areas-LAA% and airways by wall area-WA%) and CPET variables
related to the dynamic response to exercise in terms of elastic balance (Delta
rest-to-peak IC/TLC) and ventilation capacity for carbon dioxide output
(VE/VCO2slope and VE/VCO2 intercept). METHODS: We prospectively enrolled COPD
outpatients from the University Hospital of Parma. Data on anthropometrics
characteristics, lung function, HRCT (LAA% and WA%) and CPET (Delta rest-to-peak
IC/TLC, VE/VCO2 slope and VE/VCO2 intercept) were recorded. RESULTS: Fifty-one
mild to moderate COPD patients (66% males; median age 70 y; mean FEV1 56% of
pred.) were enrolled in the study. LAA% demonstrated a significant correlation
with Delta rest-to-peak IC/TLC and VE/VCO2slope (r = 0.405, p = 0.005 and r =
0.453, p = 0.001, respectively), while WA% with VE/VCO2slope (r = -0.333, p =
0.020). In multivariate regression models, after adjustment for oxygen uptake
(peak VO2) and physical capacity (peak workload), LAA was the only independent
predictor of Delta rest-to-peak IC/TLC (beta 0.774, SE 0.334, p = 0.025) and
VE/VCO2 slope (beta 0.155, SE 0.053, p = 0.005 and beta 0.305, SE 0.123, p =
0.018, respectively). VE/VCO2 intercept was instead predicted from FEV1 only
(beta -0.097, SE 0.042, p = 0.027). CONCLUSION: In mild to moderate COPD
patients, emphysema (LAA) and airways metrics (WA) have close relationships with
the different characteristics of ventilatory response to exercise. In particular,
we were able to show that LAA is an independent predictor of exercise-induced
Delta rest-to-peak IC/TLC and VE/VCO2 slope.
PMID- 27492534
TI - Pulmonary vein stenosis complicating radiofrequency catheter ablation for atrial
fibrillation: A literature review.
AB - Radiofrequency catheter ablation has become a widely used intervention in the
treatment of atrial fibrillation. Pulmonary vein stenosis (PVS) is one of the
most serious complications associated with this procedure; the degree of stenosis
ranges from mild (<50%) to complete venous occlusion. The natural history of PVS
and the risk of progression of existing PVS are uncertain. Symptomatic and/or
severe PVS is a serious medical problem and can be easily misdiagnosed since it
is an uncommon and relatively new medical problem, often has low clinical
suspicion among clinicians, and has a non-specific presentation that mimics other
more common respiratory or cardiac diseases. The estimated incidence varies in
literature reports from 0% to 42% of ablation procedures, depending on technical
aspects of the procedure and operator skill. Most patients with significant PVS
remain asymptomatic or have few symptoms. Symptomatic patients usually present
with dyspnea, chest pain, or hemoptysis and are usually treated with balloon
angioplasty and/or stent placement. Little is known about the long term effect of
PV stenosis/occlusion on the pulmonary circulation and the development of
pulmonary hypertension. Evolving technology may reduce the frequency of this
complication, but long term studies are needed to understand the effect of
therapeutic atrial injury and adverse outcomes. This review summarizes the
current literature and outlines an approach to the evaluation and management of
these patients.
PMID- 27492535
TI - A 12-year prognosis of adult-onset asthma: Seinajoki Adult Asthma Study.
AB - RATIONALE: Long-term prognosis of adult-onset asthma is poorly known. OBJECTIVE:
To evaluate 12-year prognosis of adult-onset asthma and the factors associated
with disease prognosis. METHODS: Seinajoki Adult-onset Asthma Study (SAAS) is a
12-year real-life single-center follow-up study of new-onset asthma diagnosed at
adult age and treated in primary and specialized care. Remission was defined by
no symptoms and no asthma medication use for 6 months. Asthma control was
evaluated according to Global Initiative for Asthma 2010. Factors associated with
current asthma control were analyzed by multinomial multivariate logistic
regression. MAIN RESULTS: A total of 203 patients (79% of the baseline
population) were followed for 12 years. Remission occurred in 6 (3%) patients. In
34% asthma was controlled, in 36% it was partially controlled and in 30%
uncontrolled. Uncontrolled asthma was predicted by elevated body-mass index at
baseline, smoking (pack-years) and current allergic or persistent rhinitis.
Elevated blood eosinophils and good lung function (FEV1) at baseline protected
from uncontrolled asthma. In contrast, gender, age at the onset or baseline
symptoms (Airways Questionnaire 20) were not significant predictors of
uncontrolled disease. CONCLUSIONS: During a 12-year follow-up, remission of adult
onset asthma was rare occurring in only 3% of patients. The majority of patients
(66%) presented either with uncontrolled or partially controlled asthma. This
study is registered at ClinicalTrials.gov with identifier number NCT02733016.
PMID- 27492536
TI - Healthcare burden of obstructive sleep apnea and obesity among asthma
hospitalizations: Results from the U.S.-based Nationwide Inpatient Sample.
AB - BACKGROUND: Studies have highlighted the significant comorbidities of both
obesity and obstructive sleep apnea (OSA) among asthma patients in outpatient
settings, but such data in the inpatient setting is sparse. METHODS: Using 2009
2011 U.S. Nationwide Inpatient Sample; survey-weighted regression analyses were
conducted to address the role of obesity, OSA, and both obesity and OSA on length
of stay (LOS), total hospital charges, need for respiratory therapy, and
disposition among adults with primary asthma hospitalization (n = 179,789).
RESULTS: Males had a higher prevalence of OSA than females (5.23% vs. 3.88%),
while females had a higher prevalence of obesity (17.21% vs. 8.95%) and both
obesity and OSA (7.11% vs. 6.19%). Increased hospital LOS was associated with
presence of obesity (incidence rate ratio [IRR] males = 1.07, IRR females =
1.08), OSA (IRR males = 1.07, IRR females = 1.14), and both obesity and OSA (IRR
males = 1.19, IRR females = 1.24). Increased total hospital charges was related
to obesity (8.64% for males and 9.61% for females), OSA (15.39% for males and
19.13% for females), and both comorbidities (24.94% for males and 28.50% for
females). Presence of OSA alone increased odds of need for respiratory therapy
for males (odds ratio [OR] = 2.56) and females (OR = 3.22), as did presence of
both comorbidities (OR males = 2.85, OR females = 3.60). Odds of routine
disposition was lower among females with both comorbidities (OR = 0.82).
CONCLUSION: Compared to obesity alone, OSA and both obesity and OSA are
associated with increased health resource utilization and poorer inpatient
outcomes. This demonstrates the need for further clinical investigations of early
detection of OSA among such at-risk populations.
PMID- 27492537
TI - Impact of hyponatremia on mortality and morbidity in patients with COPD
exacerbations.
AB - Hyponatremia is the most common electrolyte disorder in hospitalized patients,
being associated with increased morbidity and mortality in different clinical
conditions. However, the prevalence and impact of this electrolytic disorder in
patients hospitalized for an exacerbation of COPD still remains unknown. The aim
of the present study was to clarify these points. A total of 424 patients
hospitalized due to a COPD exacerbation were consecutively included, showing a
frequency of hyponatremia of 15.8% (hyposmolar in most cases). Even though
patients with and without hyponatremia showed a similar age, comorbidities, lung
function impairment, presence of previous exacerbations, hospitalizations, most
of the comorbidities and the overall severity index (APACHE II), their clinical
outcomes were worse. Indeed, their hospitalization length, mechanical ventilation
requirements and deaths (both during admission and within the months following
discharge) were higher than those of non-hyponatremic patients. A sodium
threshold lower than 129.7 mEq/L exhibited the better discriminatory power for
death prediction. We conclude that hyponatremia (especially if severe) is a
predictive marker for a bad clinical course in COPD exacerbations and therefore,
patients with this electrolyte abnormality should be carefully monitored.
PMID- 27492538
TI - Enhanced LPS-induced activation of IL-27 signalling in sarcoidosis.
AB - RATIONALE: Granulomas in sarcoidosis have recently been described as containing
Interleukin (IL)-27, one of the members of the IL-12 family of cytokines, which
also includes IL-35. Levels of these cytokines and the IL-27 receptor subunits
were hypothesised to differ between patients with sarcoidosis compared to healthy
controls in peripheral blood. METHODS: Using a cross-sectional study design,
plasma and peripheral blood mononuclear cells (PBMC) were collected from patients
and control subjects. Protein and mRNA (in PBMC) levels for IL-27 and IL-35
(IL27, EBI3, IL12A subunits) as well as IL-27 receptor (IL6ST and IL27RA
subunits) were assessed spontaneously and following direct (LPS) and indirect
(anti-CD3/28 activation beads) macrophage stimulation using RT- PCR, ELISA and
flow cytometry. RESULTS: Following stimulation with LPS, PBMC of patients with
sarcoidosis displayed significantly enhanced expression of IL27 and EBI3 mRNA (p
= 0.020 and p = 0.037 respectively) compared to PBMCs from healthy controls.
There was also significantly enhanced production of IL-27 by PBMC from patients
with sarcoidosis compared to healthy controls in response to LPS stimulation (p =
0.027). IL6ST mRNA and IL6ST protein were significantly lower in patients with
sarcoidosis (mRNA p = 0.0002; MFI p = 0.0015) whilst IL27RA protein levels were
significantly higher in patients with sarcoidosis compared to healthy controls
(MFI p < 0.0001). Plasma IL-35 protein levels did not differ between control and
sarcoidosis subjects (p = 0.23). CONCLUSION: These results suggest there may be
exaggerated activation of IL-27 signalling in response to LPS in sarcoidosis.
PMID- 27492539
TI - Ambrisentan response in connective tissue disease-associated pulmonary arterial
hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.
AB - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a condition which may lead to
right ventricular failure and early mortality and is an important complication in
patients with connective tissue disease (CTD). Previously, the endothelin A
selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in
treating patients with PAH due to WHO Group I etiologies. These analyses describe
the 3-year efficacy and safety of ambrisentan in patients specifically with CTD
associated PAH (CTD-PAH). METHODS: Patients with CTD-PAH participating in the
ARIES-1 and -2 clinical trials and their long-term extension were evaluated.
Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening,
and survival were collected at routine study visits. Additional analyses of 6MWD
categorical (30 m) breakpoints were conducted to determine any relationship
between 6MWD and a prognostic threshold for survival. RESULTS: 124 patients with
CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with
ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At
3 years, 64% of patients were free from clinical worsening and 76% of patients
were still alive (Kaplan-Meier estimates). Identified factors holding prognostic
relevance for survival include: baseline functional class, CTD-PAH subgroup,
patient sex, improvement in 6MWD >=30 m over the first 12 weeks of treatment, the
most recent 6MWD, and a 6MWD absolute threshold of 222 m. CONCLUSION: These first
analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed
fewer clinical worsening events and improved survival compared to historical
controls. Key exercise parameters were also identified which appear important in
guiding treatment.
PMID- 27492540
TI - Women using bleach for home cleaning are at increased risk of non-allergic
asthma.
AB - BACKGROUND: Bleach is widely used for household cleaning. Although it is
recognized that occupational use of bleach may have adverse respiratory health
effects, it is unknown whether common domestic use of bleach may be a risk factor
for asthma. AIM: To assess whether the domestic use of bleach for home cleaning
is associated with asthma and other respiratory outcomes. METHODS: Questionnaire
based information on respiratory symptoms and cleaning habits and data from skin
prick-tests, bronchial responsiveness challenge and white blood cells were
analyzed in 607 women participating in the follow-up of the Epidemiological Study
on the Genetics and Environment of Asthma (EGEA). Bleach use was evaluated in 3
categories (<1 day/week; 1-3 days/week; 4-7 days/week "frequent"). RESULTS:
Overall, 37% of the women reported using bleach weekly. Women using bleach
frequently (11%) were more likely to have current asthma as compared to non-users
(adjusted Odds-Ratio (aOR) = 1.7; 95% Confidence Interval (95%CI) 1.0-3.0). Among
women with asthma, frequent use of bleach was significantly associated with
higher blood neutrophil cell counts. Bleach use was significantly associated with
non-allergic asthma (aOR 3.3; 95%CI 1.5-7.1), and more particularly with non
allergic adult-onset asthma (aOR 4.9; 95%CI 2.0-11.6). Consistently, among women
without allergic sensitization, significant positive associations were found
between use of bleach and bronchial hyperresponsiveness, asthma like-symptoms and
chronic cough. No association was observed for allergic asthma. CONCLUSIONS:
Frequent use of bleach for home-cleaning is associated with non-allergic adult
onset asthma, elevated neutrophil counts and lower-airway symptoms in women.
PMID- 27492541
TI - Identification of five clusters of comorbidities in a longitudinal Japanese
chronic obstructive pulmonary disease cohort.
AB - BACKGROUND AND OBJECTIVES: Patients with chronic obstructive pulmonary disease
(COPD) frequently suffer from various comorbidities. Recently, cluster analysis
has been proposed to examine the phenotypic heterogeneity in COPD. In order to
comprehensively understand the comorbidities of COPD in Japan, we conducted
multicenter, longitudinal cohort study, called the Keio COPD Comorbidity Research
(K-CCR). In this cohort, comorbid diagnoses were established by both objective
examination and review of clinical records, in addition to self-report. We aimed
to investigate the clustering of nineteen clinically relevant comorbidities and
the meaningful outcomes of the clusters over a two-year follow-up period.
MATERIAL AND METHODS: The present study analyzed data from COPD patients whose
data of comorbidities were completed (n = 311). Cluster analysis was performed
using Ward's minimum-variance method. RESULTS: Five comorbidity clusters were
identified: less comorbidity; malignancy; metabolic and cardiovascular;
gastroesophageal reflux disease (GERD) and psychological; and underweight and
anemic. FEV1 did not differ among the clusters. GERD and psychological cluster
had worse COPD assessment test (CAT) and Saint George's respiratory questionnaire
(SGRQ) at baseline compared to the other clusters (CAT: p = 0.0003 and SGRQ: p =
0.00046). The rate of change in these scores did not differ within 2 years. The
underweight and anemic cluster included subjects with lower baseline ratio of
predicted diffusing capacity (DLco/VA) compared to the malignancy cluster (p =
0.036). CONCLUSIONS: Five clusters of comorbidities were identified in Japanese
COPD patients. The clinical characteristics and health-related quality of life
were different among these clusters during a follow-up of two years.
PMID- 27492543
TI - A randomized controlled study comparing Prostaglandin E2 vaginal suppository with
intra-cervical Foleys catheter balloon for preinduction cervical ripening at
term.
AB - BACKGROUND: Pre-induction ripening of an unfavourable cervix reduces the
incidence of failed induction and associated maternal and perinatal morbidity and
mortality. OBJECTIVE: The aim of this study is to compare the effectiveness of
prostaglandin E2(PGE2) vaginal suppository with intra-cervical Foley's catheter
balloon for pre-induction cervical ripening. METHODS: It is a prospective
randomized study. Clients with unfavourable cervix (Bishop score<5) were randomly
allocated into two groups. One group received 3mg PGE2 vaginal suppository and
the second group had intra cervical Foley catheter insertion and balloon inflated
with 30mls of sterile water. RESULTS: There were 38 patients in each arm.There
was no difference in age, parity and educational level, p=0.9157, 0.8054 and
0.7568 respectively, in the two groups. There were significant changes in the
Bishop scores following the application of Foley's catheter and Prostaglandin E2
(p= 0.0214 and 0.0105) respectively. The cervix became ripened (Bishop score e"5)
in 92.1% of clients. There was no significant difference in cervical ripening
effectiveness in the two groups (p=1.0000). The average time to onset of labour
(latency interval) was 12.48+/-3.36 hours and was significantly shorter with the
PGE2 group (p=0.0494). The mean induction to delivery interval for the women was
16.33+/-8.25hours. There was no significant difference between the two groups
(p=0.7418). There were no differences between the two groups in mode of delivery,
apgar sores and neonatal admission rate. CONCLUSIONS: PGE2 and Foley catheter
balloon are equally effective as cervical ripening agents.
PMID- 27492542
TI - The Secreted Protease PrtA Controls Cell Growth, Biofilm Formation and
Pathogenicity in Xylella fastidiosa.
AB - Pierce's disease (PD) is a deadly disease of grapevines caused by the Gram
negative bacterium Xylella fastidiosa. Though disease symptoms were formerly
attributed to bacteria blocking the plant xylem, this hypothesis is at best
overly simplistic. Recently, we used a proteomic approach to characterize the
secretome of X. fastidiosa, both in vitro and in planta, and identified LesA as
one of the pathogenicity factors of X. fastidiosa in grapevines that leads to
leaf scorching and chlorosis. Herein, we characterize another such factor encoded
by PD0956, designated as an antivirulence secreted protease "PrtA" that displays
a central role in controlling in vitro cell proliferation, length, motility,
biofilm formation, and in planta virulence. The mutant in X. fastidiosa exhibited
reduced cell length, hypermotility (and subsequent lack of biofilm formation) and
hypervirulence in grapevines. These findings are supported by transcriptomic and
proteomic analyses with corresponding plant infection data. Of particular
interest, is the hypervirulent response in grapevines observed when X. fastidiosa
is disrupted for production of PrtA, and that PD-model tobacco plants transformed
to express PrtA exhibited decreased symptoms after infection by X. fastidiosa.
PMID- 27492544
TI - Chlamydia Trachomatis Infection and Tubal Infertility in Port Harcourt,
Southern,Nigeria.
AB - BACKGROUND: Tubal occlusion remains one the commonest causes of infertility in
our environment and previous pelvic infection have been implicated in the
aetiology of the blockage Objective: To demonstrate prior chlamydia infection in
women with tubal factor infertility and ascertain the relationship between
chlamydia and tubal occlusion. METHODS: This was a case-control study consisting
of 188 patients drawn from the University of Port Harcourt Teaching Hospital
(UPTH) Port Harcourt, South-South Nigeria.The cases were 94 women with
radiologically confirmed tubal occlusion and the controls were another 94 women
with intrauterine pregnancy, all screened for the presence of chlamydia
immunoglobin G antibody in the serum using Immunocomb Chlamydia Bivalent IgG kit,
Orgenics, Israel.Their socio-demographic characteristics and the pattern of
sexual behaviour were documented in the profoma provided. Statistical analysis
was done using SPSS version 17 statistical software. RESULTS: The prevalence of
Chlamydia antibodies was significantly higher in patients with tubal factor
infertility (61.7%) than in the pregnant controls (34%) as p=0.001 and was
associated with a three-fold risk of tubal factor infertility, with Odd's ratio
(O.R) 3.12. CONCLUSION: There was a risk association between Chlamydia
Trachomatis infection and tubal factor infertility. Early coitarche and previous
pelvic inflammatory disease were other risk factors of Chlamydia trachomatis
infection found to be positively associated with tubal factor infertility.
PMID- 27492545
TI - Engaging Market Traders in Lassa Fever Campaign: Assessment of Knowledge and Risk
Behaviour.
AB - BACKGROUND: Markets provide a forum for reaching a large adult population with
information on Lassa fever, and therefore understanding the food handling
practices of traders may provide the foundation for an effective campaign against
Lassa fever. This study was undertaken to provide baseline information on
knowledge and food handling practices of traders in local markets in a Lassa
fever endemic state of Nigeria. STUDY DESIGN: A structured questionnaire was used
to obtain food handling habits that facilitate the transmission of Lassa virus
from a cross sectional study involving 385 traders in three major markets in Edo
state and data analyzed using SPSS version 15. RESULTS: Two hundred and ninety
three (76.1%) had ever heard of Lassa fever, 27 (9.2%) had good knowledge. Good
knowledge was significantly associated with higher educational status (p < 0.00)
and male gender (p=0.03). Thirty seven (12.6%) respondents sun-dried their food
frequently, 105 (35.8%) stored utensils in rodent proof containers, and 136
(46.4%) had the habit of eating garri soaked in water. One hundred and ninety
(49.4%) respondents had food hygiene practices that were favorable for spread of
Lassa fever. CONCLUSION: The observed gaps in knowledge of Lassa fever and food
hygiene may be addressed through tailored health messages. In this way, market
campaigns will be effective in increasing knowledge of Lassa fever, and traders
can themselves become peer educators.
PMID- 27492546
TI - Haemodynamic Changes during Awake Fibreoptic Bronchoscopy in Nigeria.
AB - INTRODUCTION: There are no reports on haemodynamic changes on West African
patients undergoing fibreoptic bronchoscopy (FOB). The aim of this study was to
document these changes in West African patients undergoing awake FOB. MATERIALS
AND METHODS: All consenting patients considered for awake FOB had their pulse
rates, blood pressures and oxygen saturations documented at various phases of
FOB, during procedures and up to 30 minutes after FOB to monitor any changes from
pre-procedure levels. The values were analysed using SPSS version 16. RESULTS:
One hundred and sixty FOB were performed on 145 patients. In non- sedated
patients, the maximum oxygen saturation fall was 6% at the level of the vocal
cord while the pulse rate rose as high as 13% at the carina. Bronchial washings
exerted the most changes in sedated patients (SPO2 fell by 4.9%, and pulse rate
rose by 11.9%). The mean arterial pressure increased occurred during bronchial
washing for both groups (18.7% for non-sedated and 15.7% for sedated patients)
CONCLUSION: Tachycardia, elevations in blood pressure and hypoxaemia are more
pronounced and occur earlier during FOB in non-sedated patients. Traversing the
vocal cords and bronchial washing evoke the most cardivascular changes during
FOB.
PMID- 27492547
TI - Knowledge of Secondary School Children in Edo State on Lassa Fever and its
Implications for Prevention and Control.
AB - BACKGROUND: Seasonal outbreaks of Lassa fever in West Africa cause significant
morbidity and mortality across all ages. In addition to present efforts to raise
awareness, school children can be targeted to become peer and family health
educators. The study was carried out to determine the knowledge of Lassa fever
among secondary school children, and household practices that increase risk of
the infection. STUDY DESIGN: In a cross sectional survey, 561 secondary school
students randomly selected from schools in Edo State were interviewed by means of
a self - administered questionnaire that sought information on knowledge of Lassa
fever and practices within the home that favour rodent contact . Data were
analyzed using Statistical Package for Social Sciences version 15. RESULTS:
Knowledge of Lassa fever was poor among 259 (49.4%) respondents, fair in 216
(41.2%) and good in 49 (9.4%). Female gender (< 0.01), monogamous family
structure (p < 0.04) , and being in senior secondary class ( p=0.01) were
predictors of high knowledge score. Self- reported Lassa fever risk conditions
were found to be of low prevalence in 311(55.4%) and high in 250 (44.6%) homes,
and associated with educational status of mother ( p=0.00) and father, (p =0.00).
CONCLUSION: School children in endemic communities lack good knowledge of Lassa
fever, but when properly guided, have the potential to become peer and family
educators.
PMID- 27492548
TI - Orbito-ocular tumors in Ibadan, South West Nigeria.
AB - AIM: The aim of this study was to review the cases of orbito-ocular tumors in a
single tertiary health facility, and determine changes in pattern of
presentation. MATERIALS AND METHODS: Medical records of all patients with
histologically confirmed orbito-ocular tumors between January 1992 and December
2011 in a tertiary center were reviewed. Patients' demographics, types of orbito
ocular tumor and their presentation were recorded. RESULTS: Records of 205
patients were analyzed with a male to female ratio of 1.1:1 and median age of
seven years. Retinoblastoma was the most common tumor followed by ocular surface
squamous neoplasia. Squamous cell carcinoma was the most common eyelid tumor
while rhabdomyosarcoma was the most common orbital tumor. No case of melanoma was
seen during the period. More than two thirds of patients had lost vision at
presentation due to delay in seeking appropriate medical attention Conclusion:
There appears to be a reduction in the cases of orbito-ocular tumors in Ibadan,
however, there is little variation in the pattern of presentation. Encouraging
early presentation to the appropriate health facility may possibly reduce the
morbidity in these patients.
PMID- 27492549
TI - The Pattern of Uveitis In An African Tertiary Eye Care Centre.
AB - OBJECTIVE: To determine the pattern of presentation of uveitis at the Guinness
Eye Centre of the Lagos University Teaching Hospital, Lagos, Nigeria. MATERIALS
AND METHODS: The case files of all patients with the diagnosis of uveitis who
presented at the center from January 2006 to December 2010 were reviewed. Data on
age, sex, ethnicity, symptoms, duration of symptoms before presentation, eye
affected, anatomical type of uveitis and clinical type of uveitis were extracted
onto a form for analysis. RESULTS: A total of 68 cases of uveitis were reviewed.
There were 38(60.3%) males and 25 (39.7%) females. The range was from 12 to 90
years. The peak incidence occurred within the age range 21-40 years inclusive.
Anterior uveitis and posterior uveitis occurred in 34(54.0%) and 17(27%) patients
respectively. While reduction in vision was reported as a symptom by 54(85.7%)
patients, only 41(65.1%) patients presented within 4 weeks of onset of symptoms.
CONCLUSION: Anterior uveitis was the most common clinical type in this study. The
highest incidence of uveitis occurred in the third and fourth decades of life.
PMID- 27492550
TI - Visual acuity, safe/unsafe practices and self-reported road traffic crash
experiences among commuter bus drivers from two motor parks in Lagos, Nigeria.
AB - BACKGROUND: Road Traffic injuries remain a significant public health problem with
serious health and economic implications. This study was conducted to determine
visual acuity, safety practices and road traffic crash (RTC) experiences of
commercial bus drivers in Lagos, Nigeria. METHODS: This cross-sectional study
involved visual acuity screening and interviewer- administered questionnaire
survey. Participating motor parks were selected by simple random sampling and all
intercity, commercial minibus drivers were included. Data was analyzed with Epi
info version 3.5.1. RESULTS: A total of 407 drivers participated with a mean age
of 43.4 +/- 10.8 years. A total of 68 (16.7%) of the drivers did not meet the
minimum VA standard required for driving; 8.6% of them use mobile phones while
driving; 97% fasten their seatbelt, out of which almost 98% do so always.
Fourteen percent also admitted eating while driving. Sixty two (15.2%) of drivers
had been involved in RTC in the past 5 years prior to interview. CONCLUSION: A
proportion of commercial minibus drivers did not meet the minimum VA required for
driving. Some of them also practiced distracted driving. Free visual acuity
screening within the motor park is recommended for commercial drivers at least
once a year. There should be awareness campaigns to enlighten commercial drivers
on the dangers of distracted driving in addition to strict enforcement of
regulations and Highway Code.
PMID- 27492551
TI - Acardius Acephalus in an Undiagnosed Twin Gestation; Case Report and review of
Literature from Federal Medical Centre Gusau, Zamfara State, Northwestern
Nigeria.
AB - BACKGROUND: Acardiusacephalusfoetal anomaly is a rare abnormality occurring in
multifoetal gestation particularly monozygous twin gestation. It is commonly
characterized by varying gross structural malformations incompatible with extra
uterine life. Reports on acardiusacephalusfoetal anomaly remain sparse. We report
a case of acardiusacephalusin an undiagnosed twin with striking gross
malformation delivered to a 28 year old un-booked multipara. Objective To report
an acardiusacephalic anomaly in the second of an undiagnosed twin pregnancy
delivered to a multipara and review relevant literature. METHOD: A Case was fully
documentedat the Federal medical centre Gusau, Nigeria and local and
international literature search conducted and reviewed. CONCLUSION:
Acardiusacephalus may have additional malformations in the other organs. The
current case, the first in our centre, shows yet other striking gross and severe
malformations characterizing acardiusacephalus.
PMID- 27492553
TI - Replication of alpha-amino acids via Strecker synthesis with amplification and
multiplication of chiral intermediate aminonitriles.
AB - Replication of chiral l- and d-alpha-(p-tolyl)glycine has been achieved in
combination with the asymmetric induction, amplification and multiplication of
their own chiral intermediates, l- and d-aminonitriles, in the solid-phase via
the Strecker reaction between three achiral components, which is a plausible
prebiotic mechanism for amino acid synthesis.
PMID- 27492552
TI - The burden of maternal morbidity and mortality attributable to hypertensive
disorders in pregnancy: a prospective cohort study from Uganda.
AB - BACKGROUND: Hypertensive disorders of pregnancy are a major cause of morbidity
and mortality. The objective was to estimate the disease burden attributable to
hypertensive disorders of pregnancy in two referral hospitals in Uganda. METHODS:
Through a prospective cohort study conducted in Jinja and Mulago hospitals in
Uganda from March 1, 2013 and February 28, 2014, hypertension-related cases were
analyzed. Maternal near miss cases were defined according to the WHO criteria.
Maternal deaths were also analyzed. The maternal near miss incidence ratio, the
case-specific severe maternal outcome ratio, the case-specific maternal mortality
ratio and the case-fatality ratio were computed. RESULTS: Of 403 women with
hypertensive disorders of pregnancy, 218 (54.1 %) had severe preeclampsia, 172
(42.7 %) had eclampsia, and 13 had chronic hypertension or Hemolysis, elevated
liver enzymes or low platelets (HELLP) syndrome. The case-specific maternal near
miss incidence ratios was 8.60 per 1,000 live births for all hypertensive
disorders, 3.06 per 1,000 live births for severe preeclampsia and 5.11 per 1,000
live births for eclampsia. The case-specific severe maternal outcome ratio was
9.37 per 1,000 live births for all hypertensive disorders, and was 3.25 per 1,000
live births for severe preeclampsia and 5.61 per 1,000 live births for eclampsia.
The case-specific maternal mortality ratio was 780 per 100,000 live births for
all hypertensive disorders, and was 1940 per 100,000 live births for severe
preeclampsia and 501 per 100,000 live births for eclampsia. The case-fatality
ratio was 5.1 % overall (for all hypertensive disorders), but was 8 times higher
for eclampsia compared to severe preeclampsia. Cyanosis, abnormal respiration,
oliguria, circulatory collapse, coagulopathy, thrombocytopenia, and elevated
serum lactate were significantly associated with severe maternal outcomes.
CONCLUSION: There is high morbidity attributable to hypertensive disorders in
pregnancy. Since some of the complications associated with morbidity can be
recognized early, it is possible to prevent severe morbidity through early
intervention with delivery, antihypertensive therapy and prophylactic magnesium
sulphate treatment. The findings highlight the feasibility of implementing a
facility-based surveillance system for severe maternal morbidity due to
hypertensive disorders.
PMID- 27492554
TI - Icariine Restores LPS-Induced Bone Loss by Downregulating miR-34c Level.
AB - Bacteria-induced inflammatory responses cause excessive bone resorption in
chronic inflammatory diseases such as septic arthritis, osteomyelitis, and
orthopedic implant failure. Icariine has been reported to facilitate the bone
healing and reduce the occurrence of osteoporosis in clinical, moreover,
laboratory studies which have proved that Icariine promotes the proliferation and
differentiation of osteoblasts in vitro. The present study aimed to evaluate the
effects of Icariine on lipopolysaccharide (LPS)-induced bone loss via an
osteogenic-in vitro model and to elucidate the underlying molecular mechanisms.
Here, we showed that Icariine restored LPS-induced bone loss in a dose-dependent
manner without any cytotoxicity even at 100 MUM in an osteogenic-in vitro model.
Interestingly, Icariine restored the protein expression of Runx2, a key
transcription factor for osteogenesis, but had no effect on its mRNA expression
level. MiRNA-34c was dramatically upregulated after LPS stimulation; however,
Icariine preincubation reversed miRNA-34c level. Western blot analysis showed
that overexpression of miR-34c markedly inhibited the expression of osteogenic
gene makers such as alkaline phosphatase (ALP), Runx2, OPN, and BMP2. ALP
activity analysis and Alizarin Red S staining exhibited that both Icariine
induced osteogenic differentiation and mineral nodule formation were
significantly inverted by overexpression of miR-34c. Western blot results also
showed that Icariine notably inhibited LPS-induced phosphorylation of JNKs, p38,
IkBalpha, IKKbeta, and p65. Taken together, our studies suggested that Icariine
restored LPS-induced bone loss by downregulating miR-34c level and suppressing
JNKs, p38, and NF-kB pathways, which highlighted the potential use of Icariine as
a therapeutic agent in the treatment of bacteria-induced bone loss diseases.
PMID- 27492555
TI - Dual-time-point 18F-FDG PET/CT in the diagnosis of solitary pulmonary lesions in
a region with endemic granulomatous diseases.
AB - OBJECTIVE: Granulomatous diseases (GDs) can be metabolically active and
indistinguishable from lung cancer on 18F-fluorodeoxyglucose positron emission
tomography (18F-FDG PET) imaging. Evaluation of solitary pulmonary lesions
remains a diagnostic challenge in regions with endemic GD. This study sought to
determine the efficacy of dual-time-point (DTP) 18F-FDG PET/computed tomography
(CT) imaging in diagnosing solitary pulmonary lesions from such regions. METHODS:
A total of 50 patients with solitary pulmonary nodules or masses with confirmed
histopathological diagnoses underwent DTP 18F-FDG PET/CT imaging at 1 and 3 h
after tracer injection. The maximum standardized uptake value (SUVmax) on early
and delayed scans (SUV1h and SUV3h, respectively) and retention index (RI) were
calculated for each pulmonary lesion. Receiver operating characteristic analysis
was performed to evaluate the discriminating validity of the parameters. RESULTS:
There were 37 malignant and 13 benign solitary pulmonary lesions. Eight of the 13
(62 %) benign lesions were GDs. The sensitivity/specificity/accuracy of SUV1h,
SUV3h and RI were 84/69/80 %, 84/85/84 %, and 81/54/74 %, respectively. SUV3h had
the best diagnostic performance, especially regarding specificity. The values of
SUV1h and SUV3h were significantly different between malignant lesions and GD,
while the RI values of malignant lesions and GD were both high (18.6 +/- 19.5 and
18.7 +/- 15.3 %, respectively; P = not significant). CONCLUSION: SUV3h appeared
to improve the diagnostic specificity of 18F-FDG PET/CT in evaluating solitary
pulmonary lesions from regions with endemic GD.
PMID- 27492556
TI - Extraction and derivatization of Leucaena leucocephala (Lam.) galactomannan:
Optimization and characterization.
AB - Water soluble gums also known as hydrocolloids are increasingly finding
applications in the pharmaceutical and food industry due to their versatile
functional properties. They possess considerable use in food and pharmaceutical
industries as emulsifying, thickening and gelling agents. In the present
investigation a heteropolysaccharide galactomannan was extracted from Leucaena
leucocephala (Lam.) seeds by an aqueous method, characterized for its
compositional analysis (mannose: galactose ratio), physicochemical and functional
properties (solubility), and mechanical properties. The extracted gum was
derivatized to form its carboxymethyl derivative and the method of its
derivatization was optimized by varying the reaction parameters. The native and
derivatized gum was characterized by FTIR, XRD, DSC, NMR, SEM and elemental
analysis, etc. The yield of Leucaena leucocephala galactomannan (LLG) was found
to be 20% (w/w). The optimized parameters for carboxymethylation reaction (degree
of substitution 0.805) were found to be 6.0g NaOH, 10.0g MCA, at 60 degrees C for
4h. The physicochemical and functional characteristics of native and derivatized
gum suggest its potential role in food and pharmaceutical industries.
PMID- 27492557
TI - Preparation of pectin/silver nanoparticles composite films with UV-light barrier
and properties.
AB - Silver nanoparticles (AgNPs) was synthesized by a green method using an aqueous
extract of Caesalpinia mimosoides Lamk (CMLE) as reducing and stabilizing agents,
and they were used for the preparation of pectin-based antimicrobial composite
films. The AgNPs were spherical in shape with the size in the range of 20-80nm
and showed the absorption peak around 500nm. The pectin/AgNPs composite film
exhibited characteristic absorption peak of AgNPs at 480nm. The surface color and
light transmittance of the pectin films were greatly influenced by the addition
of AgNPs. The lightness of the films decreased, however, redness and yellowness
of the films increased after incorporation of AgNPs. UV-light barrier property of
the pectin film increased significantly with a little decrease in the
transparency. Though there were no structural changes in the pectin film by the
incorporation of CMLE and AgNPs as indicated by the FTIR results, the film
properties such as thermal stability, mechanical strength, and water vapor
barrier properties of the pectin films increased. The pectin/AgNPs nanocomposite
films exhibited strong antibacterial activity against food-borne pathogenic
bacteria, Escherichia coli and Listeria monocytogenes.
PMID- 27492558
TI - Kinetic and thermodynamic evaluation of adsorption of Cu(II) by thiosemicarbazide
chitosan.
AB - A modified biomacromolecule, chitosan-thiosemicarbazide framework (TSCS) as an
adsorbent for Cu(II) was prepared from dialdehyde chitosan through condensation
reaction with thiosemicarbazide, stabilized by the reduction reaction with sodium
borohydride. TSCS was characterized by means of FT-IR and XPS. Surface
morphologies were studied by FESEM and BET, which revealed the highly macro
porous structure. The thermal analyses was done through TGA showing much stable
chemical configuration at about >=400 degrees C. The experimental equilibrium
data was evaluated by Langmuir, Freundlich and Dubinin-Radushkevich isotherm
models. The Langmuir adsorption model was best fitted with experimental value,
suggests the existence of monolayer coverage of adsorbed molecules with a maxima
of 142.85mgg-1. The kinetic data was analyzed using pseudo-first-order, pseudo
second-order and intraparticle diffusion models and the pseudo-second-order
kinetics were found for all the concentrations. The calculated thermodynamic
parameters such as DeltaGo, DeltaH and DeltaS were -2.33kJmol-1, 570.40Jmol-1 and
9.75Jmol-1K-1 respectively signifies the adsorption of Cu(II) onto TSCS is
endothermic, spontaneous and a process of physisorption. The regeneration
efficiency of the TSCS as an adsorbent was found to be >=90-95% using 0.1M EDTA.
PMID- 27492559
TI - Application of Chitosan/PVA Nano fiber as a potential wound dressing for
streptozotocin-induced diabetic rats.
AB - Diabetes mellitus is a worldwide health problem affecting 1-2% of the population
of world with noticeable morbidity and mortality. Vascular events such as
hypertension, nephropathy, neuropathy and retinopathy are happened in diabetic
patients. Decline in tissue blood circulation may causes hypoxia and finally may
leads to slow wound healing and amputation. PVA/Chitosan Nano fiber wound
dressings have high moisture vapor transmission rate and good antimicrobial
activity1 PCNWD substrate does not have any recognized cytotoxicity effects and
has excellent odor absorbing capability. In the present study, Streptozotocin
(STZ) is used to induce diabetes in rats, Skin ulcers are produced experimentally
in the experimentally induced diabetic and non-diabetic rats. Then PCNWD used as
wound dressing for 2 weeks period to evaluate its macroscopic and microscopic
effects on wound healing in comparison with untreated diabetic and non-diabetic
rats experimental ulcers. The findings of current study indicate significant
acceleration in diabetes wound healing on the rats treated by PVA/Chitosan Nano
fiber.
PMID- 27492561
TI - Evaluation of enzyme treatment conditions on extraction of anthocyanins from
Prunus nepalensis L.
AB - The study was designed to investigate the effect of enzyme assisted extraction of
anthocyanins from Sohiong fruit (Prunus nepalensis) under varied time,
temperature and treatment conditions. Highest anthocyanins yield was obtained by
coupling enzymatic treatment along with solvent extraction simultaneously.
Additionally, effect of enzyme type, enzyme concentration, reaction time and
temperature were evaluated subsequently in following experiments. Cellulase
treatment (10% E/S) for 180min at 4 degrees C exhibited highest yield of 984.40+/
3.84mg C3G/100gdm which accounts to 14.61% higher yield when compared to
conventional method (858.84+/-6.88mg C3G/100gdm). The study provides an
economical alternative for commercial extraction of anthocyanins from Sohiong
fruit which can be used as a colourant for various food and other products and
owing to its antioxidizing properties can be effective for the prevention and
treatment of diseases.
PMID- 27492560
TI - KGM-based magnetic carbon aerogels matrix for the uptake of methylene blue and
methyl orange.
AB - In this study, the preparation of magnetic Fe and Mn oxides (Mag-FMBO) loaded
carbon aerogels (CA) based on konjac glucomannan (KGM) and their performance for
dyes adsorption were investigated. The prepared magnetic carbon aerogels (Mag-CA)
materials were characterized by various methods, including BET surface area
analysis, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR)
and vibrating sample magnetometer (VSM). What's more, the Mag-CA materials were
used as adsorbents to remove dyes [anionic methyl orange (MO) and cationic
methylene blue (MB)] from aqueous solutions. The results showed that Mag-CA had
an excellent adsorption performance towards MO and MB. The adsorption equilibrium
data of both MO and MB can be well described by Langmuir model. The maximum MO
and MB uptake capacity of Mag-CA reached 7.42mgg-1 and 9.37mgg-1 according to
Langmuir isotherm at 303K, respectively. Thermodynamic parameters such as DeltaG,
DeltaH and DeltaS were estimated to understand the adsorption mechanism of MO and
MB. The adsorption processes of MO and MB could be well described by the pseudo
second-order model. Moreover, Mag-CA with dyes (MO or MB) were successfully
regenerated by ethanol and then easily separated from aqueous solution by
applying magnetic field.
PMID- 27492562
TI - Elucidating the impact of glucosylation on human serum albumin: A multi-technique
approach.
AB - Early glycation products as well as advance glycation end products are involved
in pathogenesis of diabetes. Most of studies carried out on AGEs and their
possible role in assessing diabetes complications, whereas only a few were
focused to highlight the role of Amadori products. In this study, an attempt has
been made to investigate a structural and immunological characterizations of
Amadori-albumin upon early glucosylation because albumin undergoes fast glycation
under hyperglycaemic condition. Amadori-albumin formation was determined by NBT
assay and Amadori adducts in glycated samples were confirmed by LC-MS. Structural
alterations in Amadori-albumin were characterized by loss in fluorescence
intensity, loss in secondary and tertiary structures, exposure of hydrophobic
patches, shifting in Amide bands and increment in hydrodynamic radius. Further,
presence to autoantibodies against Amadori-albumin in diabetes patients were
confirmed by direct binding ELISA and inhibition ELISA. Immunological studies
results showed that autoantibodies present in diabetic patients with and without
chronic kidney disease (CKD) showed significant binding with Amadori-albumin in
comparison to the native protein. Anti Amadori-albumin antibodies predominantly
present in CKD patients compare to without CKD patients. Band shift assay results
showed true interaction between Amadori-albumin and autoantibodies present in CKD
patients. Glucosylation results showed structural alterations in Amadori-albumin
and hence generation of neo-epitopes in HSA molecule. Such modifications
rendering the protein highly immunogenic that may be recognized as foreign
molecule by immune cells and induced autoantibodies in diabetic patients. These
finding signify the role of Amadori-albumin in kidney dysfunction in diabetes and
raised level of autoantibodies may be used as biomarker for progression of CKD.
PMID- 27492563
TI - Molecular characterization of Wolbachia infection in bed bugs (Cimex lectularius)
collected from several localities in France.
AB - Wolbachia symbionts are maternally inherited intracellular bacteria that have
been detected in numerous insects including bed bugs. The objective of this
study, the first epidemiological study in Europe, was to screen Wolbachia
infection among Cimex lectularius collected in the field, using PCR targeting the
surface protein gene (wsp), and to compare obtained Wolbachia strains with those
reported from laboratory colonies of C. lectularius as well as other Wolbachia
groups. For this purpose, 284 bed bug specimens were caught and studied from
eight different regions of France including the suburbs of Paris, Bouches-du
Rhone, Lot-et-Garonne, and five localities in Alpes-Maritimes. Among the samples,
166 were adults and the remaining 118 were considered nymphs. In all, 47 out of
118 nymphs (40%) and 61 out of 166 adults (37%) were found positive on wsp
screening. Among the positive cases, 10 samples were selected randomly for
sequencing. The sequences had 100% homology with wsp sequences belonging to the F
supergroup strains of Wolbachia. Therefore, we confirm the similarity of
Wolbachia strains detected in this epidemiological study to Wolbachia spp.
reported from laboratory colonies of C. lectularius.
PMID- 27492565
TI - AAOM Clinical Practice Statement: Subject: Oral lichen planus and oral cancer.
PMID- 27492566
TI - Tooth autotransplantation in the anterior maxilla and mandible: retrospective
results in young patients.
AB - OBJECTIVE: This retrospective study evaluated survival rates, prognosis, and
overall success of autotransplanted teeth in young patients missing anterior
teeth as a result of trauma, agenesis, or developmental disturbances. STUDY
DESIGN: Retrospective data were collected from the medical records of patients
who had undergone tooth autotransplantations to anterior sites between January
2001 and December 2012. Clinical variables, such as gender, age, surgical
indications, donor and recipient sites, type of anesthetics, bone augmentation,
and complications during follow-up, were assessed. RESULTS: A total of 59 donor
teeth in 46 patients (30 boys and 16 girls; average age 12.15 years) were
autotransplanted to the anterior region of the maxilla and mandible. After a mean
follow-up period of 17.35 months (range 10-61 months), all of the transplanted
teeth remained in situ with no complications. CONCLUSIONS: This study supports
the autotransplantation of teeth to the anterior alveolus as a viable option
suitable in growing patients with missing anterior teeth.
PMID- 27492564
TI - Prevalence of malaria, prevention measures, and main clinical features in febrile
children admitted to the Franceville Regional Hospital, Gabon.
AB - Recently, major progress has been made in controlling malaria in Africa. However,
in Gabon, little information is available on the role of malaria in childhood
febrile syndromes, the use and efficacy of preventive measures, and Plasmodium
species distribution. Here, we characterized malaria in febrile children in
Franceville, Gabon through a cross-sectional study at the pediatric unit of the
Franceville Regional Hospital. We registered 940 febrile children. Their general
condition was markedly altered in 11.7% of cases (n = 89/760); among them 19
(21.4%) had a severely altered condition. Malaria was the second most frequent
etiology (22.0%; n = 162/738), after respiratory tract infections (37.3%; n =
275/738). Children with malaria (63 +/- 39 months) were older than children
without malaria (40 +/- 37 months) (p = 0.0013). Hemoglobin, red blood cell,
white blood cell, and platelet values were lower in children with malaria than in
those without malaria (p < 0.0001). Anemia was the most common feature of severe
malaria (70.6%; n = 12/17), followed by neurological involvement (23.5%; n =
4/17). The prevalence of malaria was significantly higher in children older than
60 months than in younger children (40% vs. 15.5%; p < 0.0001). Plasmodium
falciparum accounted for 97.5% of cases (158/162), followed by Plasmodium
malariae (2.5%; n = 4/162). Bed net use was high (74.4%; n = 697/936) and
contributed to malaria prevention (p = 0.001). Good basic knowledge of malaria
also had a preventive effect (p < 0.0001). The prevalence of malaria in children
in Franceville did not decrease significantly from 2009 to 2012, remaining at
about 20%, highlighting that preventive measures should be reinforced.
PMID- 27492567
TI - Comparison of functional change in parotid gland after surgical excision of
pleomorphic adenoma by two different types of parotidectomy.
AB - OBJECTIVE: To compare the functional changes in parotid gland after surgical
excision of pleomorphic adenoma by partial superficial parotidectomy (PSP), or
conventional superficial parotidectomy (CSP). STUDY DESIGN: A prospective study
including 117 patients undergoing CSP or PSP was performed. The uptake rate (UR)
and excretion fraction (EF) of the parotid gland were measured by salivary gland
scintigraphy before the surgery, as well as at months 3, 6, and 12 after the
surgery; DeltaUR and DeltaEF, defined as the UR and EF differences between the
contralateral side and the operated side, were also calculated. RESULTS: Either
UR or EF of the operated side was lower than that in the contralateral side after
surgery (P < .05). DeltaEF and DeltaUR values at months 6 and 12 were
significantly smaller in the PSP group than those in the CSP group. CONCLUSIONS:
PSP is preferable for preservation of the functions of the parotid gland.
PMID- 27492568
TI - A versatile modular bioreactor platform for Tissue Engineering.
AB - Tissue Engineering (TE) bears potential to overcome the persistent shortage of
donor organs in transplantation medicine. Additionally, TE products are applied
as human test systems in pharmaceutical research to close the gap between animal
testing and the administration of drugs to human subjects in clinical trials.
However, generating a tissue requires complex culture conditions provided by
bioreactors. Currently, the translation of TE technologies into clinical and
industrial applications is limited due to a wide range of different tissue
specific, non-disposable bioreactor systems. To ensure a high level of
standardization, a suitable cost-effectiveness, and a safe graft production, a
generic modular bioreactor platform was developed. Functional modules provide
robust control of culture processes, e.g. medium transport, gas exchange,
heating, or trapping of floating air bubbles. Characterization revealed improved
performance of the modules in comparison to traditional cell culture equipment
such as incubators, or peristaltic pumps. By combining the modules, a broad range
of culture conditions can be achieved. The novel bioreactor platform allows using
disposable components and facilitates tissue culture in closed fluidic systems.
By sustaining native carotid arteries, engineering a blood vessel, and generating
intestinal tissue models according to a previously published protocol the
feasibility and performance of the bioreactor platform was demonstrated.
PMID- 27492569
TI - Predicting malignant neck lymphadenopathy using color duplex sonography based on
multivariate analysis.
AB - PURPOSE: To select the best predictors of cervical lymph node malignancy based on
gray-scale and power Doppler sonography using multivariate analysis. METHODS: We
evaluated sonographically a total of 97 lymph nodes in the neck that were
subjected to fine-needle aspiration biopsy. The gray-scale and power Doppler
sonography parameters that we analyzed using multivariate logistic regression
included size, shape, echogenicity, echotexture, margins, hilum, presence of
microcalcifications or necrosis, vascularization, and resistance index (RI).
RESULTS: The three variables with a diagnostic accuracy exceeding 80% were an
altered vascularization, heterogeneous echotexture, and abnormal hilum. Malignant
nodes exhibited higher RI and larger sizes than benign nodes, and the best cutoff
values to distinguish malignant from benign lymph nodes were an RI of 0.77 and a
short axis >= 0.9 cm. Altered vascularization, a short axis >= 0.9 cm, and
abnormal hilum were the best predictors of malignancy. CONCLUSIONS: The best
sonographic predictors of lymph node malignancy are, in descending order, an
altered vascularization, a short axis >= 0.9 cm, an abnormal hilum, and a
heterogeneous echotexture. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound
44:587-594, 2016.
PMID- 27492570
TI - Clinical Interpretation of Variants from Next-Generation Sequencing: The 2016
Scientific Meeting of the Human Genome Variation Society.
AB - The 2016 scientific meeting of the Human Genome Variation Society (HGVS;
http://www.hgvs.org) was held on the 20th of May in Barcelona, Spain, with the
theme of "Clinical Interpretation of Variants from Next-Generation Sequencing."
PMID- 27492571
TI - Early U.S. Experience Following FDA Approval of the ABBOTT Vascular Bioresorbable
Vascular Scaffold: Optimal Deployment Technique Using High Resolution Coronary
Artery Imaging.
AB - Drug eluting metallic stents have been the "gold standard" in the percutaneous
management of coronary artery disease. Recent publications have suggested that
the ABSORBTM bioresorbable vascular scaffold (BVS) may represent a reasonable
alternative, in well selected cases.
PMID- 27492572
TI - Developing Valid Measures of Emergency Management Capabilities within US
Department of Veterans Affairs Hospitals.
AB - Introduction Hospitals play a critical role in providing health care in the
aftermath of disasters and emergencies. Nonetheless, while multiple tools exist
to assess hospital disaster preparedness, existing instruments have not been
tested adequately for validity. Hypothesis/Problem This study reports on the
development of a preparedness assessment tool for hospitals that are part of the
US Department of Veterans Affairs (VA; Washington, DC USA). METHODS: The authors
evaluated hospital preparedness in six "Mission Areas" (MAs: Program Management;
Incident Management; Safety and Security; Resiliency and Continuity; Medical
Surge; and Support to External Requirements), each composed of various observable
hospital preparedness capabilities, among 140 VA Medical Centers (VAMCs). This
paper reports on two successive assessments (Phase I and Phase II) to assess the
MAs' construct validity, or the degree to which component capabilities relate to
one another to represent the associated domain successfully. This report
describes a two-stage confirmatory factor analysis (CFA) of candidate items for a
comprehensive survey implemented to assess emergency preparedness in a hospital
setting. RESULTS: The individual CFAs by MA received acceptable fit statistics
with some exceptions. Some individual items did not have adequate factor loadings
within their hypothesized factor (or MA) and were dropped from the analyses in
order to obtain acceptable fit statistics. The Phase II modified tool was better
able to assess the pre-determined MAs. For each MA, except for Resiliency and
Continuity (MA 4), the CFA confirmed one latent variable. In Phase I, two sub
scales (seven and nine items in each respective sub-scale) and in Phase II, three
sub-scales (eight, four, and eight items in each respective sub-scale) were
confirmed for MA 4. The MA 4 capabilities comprise multiple sub-domains, and
future assessment protocols should consider re-classifying MA 4 into three
distinct MAs. CONCLUSION: The assessments provide a comprehensive and consistent,
but flexible, approach for ascertaining health system preparedness. This approach
can provide an organization with a clear understanding of areas for improvement
and could be adapted into a standard for hospital readiness. Dobalian A , Stein
JA , Radcliff TA , Riopelle D , Brewster P , Hagigi F , Der-Martirosian C .
Developing valid measures of emergency management capabilities within US
Department of Veterans Affairs hospitals. Prehosp Disaster Med. 2016;31(5):475
484.
PMID- 27492573
TI - Decreased snake venom metalloproteinase effects via inhibition of enzyme and
modification of fibrinogen.
AB - Since the introduction of antivenom administration 120 years ago to treat
venomous snake bit, it has been the gold standard for saving life and limb.
However, this therapeutic approach is not always effective and not without
potential life-threatening side effects. We tested a new paradigm to abrogate the
plasmatic anticoagulant effects of fibrinogenolytic snake venom
metalloproteinases by modification of fibrinogen with iron and carbon monoxide
and by inhibiting these Zn(2+) dependent metalloproteinases directly with carbon
monoxide exposure. Assessment of the fibrinogenolytic effects of venoms collected
from Puff adder, Gaboon viper and Indian cobra snakes on plasmatic coagulation
kinetics was performed with thrombelastography. Pretreatment of plasma with iron
and carbon monoxide exposure markedly attenuated the effects of all three venoms,
and direct pretreatment of each venom with carbon monoxide also significantly
decreased the ability to compromise coagulation. These results demonstrated that
the introduction of a transition metal (e.g., modulation of the alpha-chain of
fibrinogen with iron), modulation of transition metal in heme (e.g., carbon
monoxide modulation of fibrinogen-bound heme iron), and direct inhibition of
transition metal containing venom enzymes (e.g., CO binding to Zn(2+) or
displacing Zn(2+) from the catalytic site) significantly decreased
fibrinogenolytic activity. This biometal modulation strategy to attenuate the
anticoagulant effects of snake venom metalloproteinases could potentially
diminish hemostatic injury in envenomed patients until antivenom can be
administered.
PMID- 27492574
TI - Sweet Taste Perception is Associated with Body Mass Index at the Phenotypic and
Genotypic Level.
AB - Investigations on the relationship between sweet taste perception and body mass
index (BMI) have been inconclusive. Here, we report a longitudinal analysis using
a genetically informative sample of 1,576 adolescent Australian twins to explore
the relationship between BMI and sweet taste. First, we estimated the phenotypic
correlations between perception scores for four different sweet compounds
(glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame) and
BMI. Then, we computed the association between adolescent taste perception and
BMI in early adulthood (reported 9 years later). Finally, we used twin modeling
and polygenic risk prediction analysis to investigate the genetic overlap between
BMI and sweet taste perception. Our findings revealed that BMI in early adulthood
was significantly associated with each of the sweet perception scores, with the
strongest correlation observed in aspartame with r = 0.09 (p = .007). However,
only limited evidence of association was observed between sweet taste perception
and BMI that was measured at the same time (in adolescence), with the strongest
evidence of association observed for glucose with a correlation coefficient of r
= 0.06 (p = .029) and for aspartame with r = 0.06 (p = .035). We found a
significant (p < .05) genetic correlation between glucose and NHDC perception and
BMI. Our analyses suggest that sweet taste perception in adolescence can be a
potential indicator of BMI in early adulthood. This association is further
supported by evidence of genetic overlap between the traits, suggesting that some
BMI genes may be acting through biological pathways of taste perception.
PMID- 27492575
TI - Place-making with older persons: Establishing sense-of-place through
participatory community mapping workshops.
AB - Principles of aging-in-place emphasize the importance of creating sustainable
environments that enable older people to maintain a sense of belonging, autonomy,
independence, safety and security. Simply altering the built environment is
insufficient for creating more inclusive environments for older persons, as
creating 'meaningful' places for aging involves consideration of psychosocial and
cultural issues that go beyond issues of physical space. This paper illustrates
how applications of community-based participatory research methods, in
particular, participatory community mapping workshops (PCMWs), can be used to
access experiences of place, identify facilitators and barriers to accessing the
built environment and co-create place-based solutions among older people and
service providers in a new affordable housing development in Western Canada.
Founded on tenets of empowerment and relationship building, four PCMWs were
undertaken with 54 participants (N = 38 older people; N = 16 local service
providers). PCMWs comprised (i) experiential group walks around the community to
access understandings of place and community and (ii) mapping exercises, whereby
participants articulated their place-based needs within the context of the new
affordable housing development and surrounding neighbourhood. Dialogues were
digitally recorded, transcribed and thematically analysed. Visual data, including
photographs taken during experiential group walks were categorized and integrated
into the narrative to illustrate place meanings. PCMWs enabled senior housing and
social care professionals and decision-makers to co-construct knowledge with
older tenants that facilitated place action and change. Key themes identified by
participants included: identifying services and needs for health and wellbeing,
having opportunities for social participation and overcoming cross-cultural
challenges. PCMWs were found to be a nuanced method of identifying needs and
resources and generating knowledge.
PMID- 27492576
TI - Advancing the evidentiary base for tobacco warning labels: A commentary.
PMID- 27492577
TI - Rapid and accurate identification of Xanthomonas citri subspecies citri by
fluorescence in situ hybridization.
AB - : Citrus canker is an economically important disease caused by the bacterial
pathogen Xanthomonas citri subsp. citri (Xcc). This organism targets a wide range
of citrus plants, including sweet orange, grapefruit, lemon and lime. As Xcc is
spread by environmental factors such as wind and rain, it is difficult to control
its movement once the disease has established. In order to facilitate monitoring
of citrus canker we sought to design a novel diagnostic protocol based on
fluorescence in situ hybridization (FISH) for identification of bacterial cells
directly from canker pustules without cultivation or DNA extraction. This method
was validated for specificity against a range of Xanthomonas species and strains.
We show that our assay is extremely rapid (typically requiring between 2 and 3
h), and possesses a similar specificity to existing PCR diagnostic tools. The
sensitivity of the assay is comparable to that of an existing PCR-based technique
and sufficient for identifying Xcc in symptomatic plant material. The method is
easily transferable to diagnosticians without prior experience using FISH.
SIGNIFICANCE AND IMPACT OF THE STUDY: Xanthomonas citri subsp. citri (Xcc) is an
aggressive and hardy pathogen of citrus plants worldwide. Outbreaks are difficult
and costly to contain and the establishment of citrus canker results in
restricted trade. In order to extend the existing toolkit for identification of
Xcc we developed a novel diagnostic approach based on fluorescence in situ
hybridization. Our approach is of comparable specificity and sensitivity to
existing methods but can be performed directly on infected tissue making it
significantly faster than existing PCRs, and requiring fewer laboratory
resources.
PMID- 27492578
TI - O6-Methylguanine-DNA methyltransferase (MGMT): A drugable target in lung cancer?
AB - This manuscript addresses the role of O6-methylguanine-DNA methyltransferase
(MGMT) as a biomarker in the oncogenesis of cancer and the opportunity of turning
this gene into a drugable target in neuroendocrine tumours of the lung. Studies
in brain tumours conclude that MGMT promoter methylation is considered a strong
predictive factor for a favourable outcome for treatment with temozolomide, e.g.
alkylating agent. We conducted a systematic review of MGMT in non-small cell lung
cancer (NSCLC), small-cell lung cancer (SCLC) and other pulmonary neuroendocrine
tumours (NETs) to evaluate whether MGMT is a prognostic and/or predictive factor
to select patients with lung cancer who can benefit from treatment with
temozolomide. In NSCLC MGMT promoter methylation is not a prognostic and
predictive factor, hence temozolomide has no place. In SCLC and NET patients with
a MGMT promoter methylation benefit of temozolomide has to be
confirmed.Temozolomide can be considered a 'personalized' treatment if the
predictive role of MGMT is further confirmed.
PMID- 27492579
TI - Serum and xeno-free, chemically defined, no-plate-coating-based culture system
for mesenchymal stromal cells from the umbilical cord.
AB - OBJECTIVES: Umbilical cord mesenchymal stromal cells (UCMSCs) can be considered
to become a new gold standard for MSC-based therapies. A serum and xeno-free,
chemically defined and no-plate-coating-based culture system will greatly
facilitate development of robust, clinically acceptable bioprocesses for
reproducibly generating quality-assured UCMSCs. MATERIALS AND METHODS: In this
study, we report for the first time, such a serum-free, xeno-free, completely
chemically defined and no-plate-coating-based culture system for the isolation
and expansion of UCMSCs, whose biological characteristics were evaluated and
compared with serum-containing medium (SCM) methods. RESULTS: This culture system
not only supported UCMSC primary cultures but also allowed for their expansion at
low seeding density. Compared to SCM, UCMSCs in SFM exhibited (i) higher
proliferative and colony-forming capacities; (ii) distinctly different
morphologies; (iii) similar phenotype; (iv) similar pluripotency-associated
marker expression; (v) superior osteogenic, but reduced adipogenic
differentiation capacitities. In addition, UCMSCs cultured in SFM retained
similar immunomodulatory properties to those in SCM. CONCLUSIONS: Our findings
demonstrate the feasibility of isolating and expanding UCMSCs in a completely
serum-free, xeno-free, chemically defined and no-plate-coating-based culture
system and represent an important step forward for development of robust,
clinically acceptable bioprocesses for UCMSCs. Further, this provides a superior
study platform for UCMSCs biology in a controlled environment.
PMID- 27492580
TI - Iridoids and phenylethanoid glycosides from the aerial parts of Ajuga tenorei, an
endemic Italian species.
AB - We report the first analysis in absolute, and in particular, concerning the
phytochemical pattern, about an endemic Italian species, Ajuga tenorei C. Presl.
The analysis, performed by means of techniques such as Column Chromatography and
NMR spectroscopy and Mass spectrometry, led to the isolation and the
identification of five compounds namely verbascoside (1), echinacoside (2),
ajugoside (3), harpagide (4) and 8-O-acetylharpagide (5). The presence of these
compounds is important from both chemotaxonomic and ethno-pharmacological point
of view. For what concerns the first point is confirmed the correct botanical
classification of the species. The isolated compounds are also known to exert
peculiar pharmacological activities and their presence may give a rationale to
the historical medicinal properties associated to the Ajuga genus in general,
since these plants have a long traditional use in many parts of the world. Such
fact might suggest the use of also this species in this sense.
PMID- 27492581
TI - A distinct sortase SrtB anchors and processes a streptococcal adhesin AbpA with a
novel structural property.
AB - Surface display of proteins by sortases in Gram-positive bacteria is crucial for
bacterial fitness and virulence. We found a unique gene locus encoding an amylase
binding adhesin AbpA and a sortase B in oral streptococci. AbpA possesses a new
distinct C-terminal cell wall sorting signal. We demonstrated that this C
terminal motif is required for anchoring AbpA to cell wall. In vitro and in vivo
studies revealed that SrtB has dual functions, anchoring AbpA to the cell wall
and processing AbpA into a ladder profile. Solution structure of AbpA determined
by NMR reveals a novel structure comprising a small globular alpha/beta domain
and an extended coiled-coil heliacal domain. Structural and biochemical studies
identified key residues that are crucial for amylase binding. Taken together, our
studies document a unique sortase/adhesion substrate system in streptococci
adapted to the oral environment rich in salivary amylase.
PMID- 27492582
TI - The primary factor for suture configuration at rotator cuff repair: Width of
mattress or distance from tear edge.
AB - OBJECTIVES: The aims of this study was first to investigate whether the bite size
or the bite distance from the tear edge is of primary importance in mattress
suture configuration for rotator cuff repair. Secondly, whether the use of a 450
left side bent Arthro-PierceTM (Smith & Nephew, Andover, USA) during suture
passage can be more effective on the strength of the configuration compared to a
straight Arthro-PierceTM. MATERIALS AND METHODS: Twenty-eight bovine
infraspinatus muscle tendons were randomized into four groups. Group 1; 5 mm wide
'bite size' * 15 mm length 'distance from the tear edge's mattress'; Group 2: 7.5
mm * 10 mm; Group 3: 15 mm * 5 mm 'using straight Arthro-PierceTM' and Group 4: 5
mm * 15 mm using left sided 450 bent Arthro-PierceTM. The repair specimens
underwent cyclic loading prior to loading the failure testing. Cyclic elongation
(mm), peak-to-peak displacement (mm), ultimate load (N), stiffness (N/mm) and
failure mode were recorded for each specimen. RESULTS: The mean ultimate load in
Group 1 was higher compared to group 3. The peak to peak displacement was higher
in Group 4 compared to Group 1 (p < 0.05). The predominant failure mode in Groups
1, 2 and 4 was suture rupture. The Group 3 most specimens failed due to suture
cut through the tendon. CONCLUSION: Bite size from the edge of the tendon seems
to be more important than the width of the mattress. The curve of the suture
passing device may also have an effect on the strength of the suture tendon
interface.
PMID- 27492583
TI - Total hip arthroplasty in patients with ankylosing spondylitis: Midterm
radiologic and functional results.
AB - INTRODUCTION: The aim of this study was to evaluate the clinical and radiological
outcomes of total hip arthroplasty (THA) in patients with Ankylosing Spondylitis
(AS). PATIENTS AND METHODS: One hundred five hips of 61 AS patients (mean age:
41.3 +/- 10.2 years) who underwent THA between 1997 and 2012 were included into
the study. Dorr's classification of proximal femoral geometry, acetabular
protrusio, bone ankylosis, acetabular protrusion, Brooker classification of
heterotopic ossification (HO), Gruen and Charnley classifications of implant
loosening were used in radiographic assessments. Patients were called back to
return for an additional long-term follow-up for functional assessment. RESULTS:
Cementless total hip arthroplasty was used in 83 hips (79%) and cemented TKA was
used in 22 hips (21%). The overall rate of aseptic loosening was 7.6% at a mean
follow-up of 5.4 years. Femoral loosening was statistically similar in cemented
and cementless femoral components (14% vs. 8%, p = 0.089). Acetabular component
loosening was statistically higher in patients with any degree of HO (p = 0.04).
Regardless of the type of femoral implant (cemented or cementless), femoral
component loosening was higher in Dorr's type C patients (p = 0.005). The average
pre-operative HSS was 46.6 +/- 16.3, and it improved to 80.7 +/- 18.7 at last
follow-up (p < 0.01). CONCLUSION: Revision incidence was similar in between
ankylosed and non-ankylosed hips. While complication rates are high, significant
functional improvement can be achieved after THA in patients with AS.
PMID- 27492584
TI - Safety of modified Stoppa approach for Ganz periacetabular osteotomy: A
preliminary cadaveric study.
AB - OBJECTIVE: The aim of this cadaveric study was to investigate the efficacy of the
modified Stoppa approach in Ganz periacetabular osteotomy (PAO). METHODS: The
Ganz PAO was performed on 10 hemipelvises with normal hips, from 5 cadavers using
the modified Stoppa approach through the Pfannenstiel incision. All of the
osteotomies were performed under fluoroscopic control and direct visualizing the
osteotomy site from the same incision. After the osteotomy, the acetabulum was
medialized and redirected anterolaterally, and fixed with 2 screws. The
neurovascular structures and the joints were examined by dissecting the soft
tissues after fixation of the osteotomies. Outcome parameters were center-edge
(CE) angle, the distances between the osteotomy and anterior superior iliac spine
(ASIS), and between the osteotomy and the sciatic notch, neurovascular and joint
penetrations. RESULTS: After the osteotomy, the mean CE angle was improved from
19.8 degrees to 25.2 degrees , mean distance between the osteotomy and ASIS was
3.1 cm, and the mean distance between the osteotomy and the sciatic notch was
10.2 mm. The neurovascular structures and the joints were examined by dissecting
the soft tissues after fixation of the osteotomies. No damage to the joint,
surrounding arteries, veins or nerves was detected in any of the cadavers.
CONCLUSIONS: Bilateral dysplastic hips can be treated with a 10 cm, cosmetically
more acceptable incision in the same session using this approach. Quadrilateral
surface of the acetabulum can be directly seen using this approach and the
osteotomy can be safely performed.
PMID- 27492585
TI - Tyrosinase inhibitory flavonoid from Juniperus communis fruits.
AB - The fruits of Juniperus communis have been traditionally used in the treatment of
skin diseases. In our preliminary experiment, the MeOH extract of J. communis
effectively suppressed mushroom tyrosinase activity. Three monoflavonoids and
five biflavonoids were isolated from J. communis by bioassay-guided isolation and
their inhibitory effect against tyrosinase was evaluated. According to the
results of all isolates, hypolaetin 7-O-beta-xylopyranoside isolated from J.
communis exhibited most potent effect of decreasing mushroom tyrosinase activity
with an IC50 value of 45.15 MUM. Further study provided direct experimental
evidence for hypolaetin 7-O-beta-D-xylopyranoside-attenuated tyrosinase activity
in alpha-MSH-stimulated B16F10 murine melanoma cell. Hypolaetin 7-O-beta-D
xylopyranoside from the EtOAc fraction of J. communis was also effective at
suppressing alpha-MSH-induced melanin synthesis. This is the first report of the
enzyme tyrosinase inhibition by J. communis and its constituent. Therapeutic
attempts with J. communis and its active component, hypolaetin 7-O-beta-D
xylopyranoside, might be useful in treating melanin pigmentary disorders.
PMID- 27492586
TI - Artificial Force Induced Reaction Method for Systematic Determination of Complex
Reaction Mechanisms.
AB - Nowadays, computational studies are very important for the elucidation of
reaction mechanisms and selectivity of complex reactions. However, traditional
computational methods usually require an estimated reaction path, mainly driven
by limited experimental implications, intuition, and assumptions of stationary
points. However, the artificial force induced reaction (AFIR) method in the
global reaction route mapping (GRRM) strategy can be used for unbiased and
automatic reaction path searches for complex reactions. In this account, we
highlight applications of the AFIR method to a variety of reactions (organic,
organometallic, enzymatic, and photochemical) of complex molecular systems. In
addition, the AFIR method has been successfully used to rationalise the origin of
stereo- and regioselectivity. The AFIR method can be applied from small to large
molecular systems, and will be a very useful tool for the study of complex
molecular problems in many areas of chemistry, biology, and material sciences.
PMID- 27492587
TI - Synthesis of "neoprofen", a rigidified analogue of ibuprofen, exemplifying
synthetic methodology for altering the 3-D topology of pharmaceutical substances.
AB - 3,3-Dimethylcyclopentanes (neopentylenes) are ubiquitous in Nature but largely
absent from synthetic pharmaceutical libraries. Neopentylenes define a
hydrophobic and rigid 3-D topology with distinct molecular pharmacology, as
exemplified here with two neopentylene-fused analogues of the synthetic anti
inflammatory drug, ibuprofen.
PMID- 27492588
TI - Trends in the match rate and composition of candidates matching into categorical
general surgery residency positions in the United States.
AB - BACKGROUND: The aim of this study was to analyze the trends in the proportion of
students from various educational backgrounds who matched into categorical
general surgery (GS) residency positions. METHODS: National Resident Matching
Program reports (1994 to 2014) were analyzed, and regression was used to estimate
the trends for each group. RESULTS: The match rate into GS-categorical residency
has remained stable; however, since 1994, we witnessed a 13% decrease in US
seniors matching into GS. This has corresponded to proportional increases in
matches for US citizens from international medical schools (US IMG, 1350%) and a
62% increase for non-US citizen international medical graduates (non-US IMG) into
GS. In comparison, US IMG matches into all first-year postgraduate positions
increased by 468%, whereas non-US IMG matches decreased by 15%. CONCLUSIONS: The
stable match rates into categorical GS residencies are not because of US seniors
but rather because of a rise in the number of IMGs. In contrast to the decreased
reliance on non-US IMGs in all other specialties, GS is accepting a larger
proportion of non-US IMGs.
PMID- 27492589
TI - Motor Neuron Disease: New insights into genetic risk factors for amyotrophic
lateral sclerosis.
PMID- 27492590
TI - Brain imaging: Synaptic density directly visualized in human brains.
PMID- 27492591
TI - What is the meaning of becoming PubMed Central journal?
PMID- 27492592
TI - Human native kappa opioid receptor functions not predicted by recombinant
receptors: Implications for drug design.
AB - If activation of recombinant G protein-coupled receptors in host cells (by drugs
or other ligands) has predictive value, similar data must be obtained with native
receptors naturally expressed in tissues. Using mouse and human recombinant kappa
opioid receptors transfected into a host cell, two selectively-acting compounds
(ICI204448, asimadoline) equi-effectively activated both receptors, assessed by
measuring two different cell signalling pathways which were equally affected
without evidence of bias. In mouse intestine, naturally expressing kappa
receptors within its nervous system, both compounds also equi-effectively
activated the receptor, inhibiting nerve-mediated muscle contraction. However,
whereas ICI204448 acted similarly in human intestine, where kappa receptors are
again expressed within its nervous system, asimadoline was inhibitory only at
very high concentrations; instead, low concentrations of asimadoline reduced the
activity of ICI204448. This demonstration of species-dependence in activation of
native, not recombinant kappa receptors may be explained by different mouse/human
receptor structures affecting receptor expression and/or interactions with
intracellular signalling pathways in native environments, to reveal differences
in intrinsic efficacy between receptor agonists. These results have profound
implications in drug design for kappa and perhaps other receptors, in terms of
recombinant-to-native receptor translation, species-dependency and possibly, a
need to use human, therapeutically-relevant, not surrogate tissues.
PMID- 27492593
TI - MoS2 memristor with photoresistive switching.
AB - A MoS2 nanosphere memristor with lateral gold electrodes was found to show
photoresistive switching. The new device can be controlled by the polarization of
nanospheres, which causes resistance switching in an electric field in the dark
or under white light illumination. The polarization charge allows to change the
switching voltage of the photomemristor, providing its multi-level operation. The
device, polarized at a voltage 6 V, switches abruptly from a high resistance
state (HRSL6) to a low resistance state (LRSL6) with the On/Off resistance ratio
of about 10 under white light and smooth in the dark. Analysis of device
conductivity in different resistive states indicates that its resistive state
could be changed by the modulation of the charge in an electric field in the dark
or under light, resulting in the formation/disruption of filaments with high
conductivity. A MoS2 photomemristor has great potential as a multifunctional
device designed by using cost-effective fabrication techniques.
PMID- 27492594
TI - Development of immobilized-pepsin microreactors coupled to nano liquid
chromatography and tandem mass spectrometry for the quantitative analysis of
human butyrylcholinesterase.
AB - Human butyrylcholinesterase is a serine hydrolase that reacts with
organophosphorus compounds (OP) to form stable adducts. These adducts are
valuable biomarkers for OP exposure and can be analyzed by liquid chromatography
tandem mass spectrometry (LC-MS/MS) after a preliminary digestion step in
solution. However, this digestion step is time-consuming and cannot be directly
coupled with LC-MS set ups. Therefore, the aim of this work was to develop pepsin
based immobilized enzyme microreactors (IMERs) for the rapid digestion of human
butyrylcholinesterase (HuBuChE). Various IMERs were synthesized by grafting
different amounts of pepsin on a CNBr-sepharose gel and the grafting yield was
measured by a bicinchoninic acid assay (BCA). A sensitive nanoLC-MS/MS method was
developed to evaluate the digestion yields of HuBuChE on IMERs which was made
possible by a synthetic peptide which was used as a calibrant. The digestion was
optimized by studying the impact of different parameters such as the digestion
time, the temperature and the amount of pepsin grafted on IMER. This optimization
allowed HuBuChE to be digested with-in 20min without pretreatment and with
digestion yields up to 20%. The repeatability of the IMER synthesis and HuBuChE
digestion was highlighted with the characterization of 3 similar IMERs. Finally,
the digestion yields of HuBuChE were higher with IMERs when compared to a typical
in solution digestion.
PMID- 27492595
TI - Sulfobutylether-beta-cyclodextrin as a chiral selector for separation of amino
acids and dipeptides in chromatography.
AB - Various amino acids, dipeptides and their isomers were (enantio)separated using
sulfobutylether-beta-cyclodextrin as a chiral selector. Two different approaches
were employed: first, dynamic coating of sulfobutylether-beta-cyclodextrin onto a
strong anion-exchange stationary phase and, second, use of sulfobutylether-beta
cyclodextrin as a mobile phase additive in a separation system with a C18 column.
Measurements were carried out using RP-HPLC and hydrophilic interaction liquid
chromatography. Mobile phases composed of organic modifier (methanol) and four
different aqueous parts: (i) deionized water, (ii) an aqueous solution of formic
acid (pH 2.1), (iii) ammonium acetate buffer (pH 4.7), and (iv) ammonium acetate
buffer (pH 8.8) in various volume ratios. Under these separation conditions, out
of 23 chiral analytes, 9 were baseline enantio-resolved and 7 were partially
separated. Of 9 mixtures of dipeptide isomers, 8 were baseline-separated.
Sulfobutylether-beta-cyclodextrin proved to be suitable for the separation of
chiral and also achiral analytes. The use of sulfobutylether-beta-cyclodextrin as
a dynamic coating agent or as a mobile phase additive depends on the particular
chromatographic system and analytes of interest.
PMID- 27492596
TI - Rapid method for the simultaneous detection of boar taint compounds by means of
solid phase microextraction coupled to gas chromatography/mass spectrometry.
AB - Because of animal welfare issues, the voluntary ban on surgical castration of
male piglets, starting January 2018 was announced in a European Treaty. One
viable alternative is the fattening of entire male pigs. However, this can cause
negative consumer reactions due to the occurrence of boar taint and possibly lead
to severe economic losses in pig husbandry. In this study, headspace solid phase
microextraction (HS-SPME) coupled to GC-MS was used in the development and
optimization of a candidate method for fast and accurate detection of the boar
taint compounds. Remarkably fast extraction (45s) of the boar taint compounds
from adipose tissue was achieved by singeing the fat with a soldering iron while
released volatiles were extracted in-situ using HS-SPME. The obtained method
showed good performance characteristics after validation according to CD
2002/657/EC and ISO/IEC 17025 guidelines. Moreover, cross-validation with an in
house UHPLC-HR-Orbitrap-MS method showed good agreement between an in-laboratory
method and the new candidate method for the fast extraction and detection of
skatole and androstenone, which emphasizes the accuracy of this new SPME-GC-MS
method. Threshold detection of the boar taint compounds on a portable GC-MS could
not be achieved. However, despite the lack of sensitivity obtained on the latter
instrument, a very fast method with run-to-run time of 3.5min for the detection
of the boar taint compounds was developed.
PMID- 27492597
TI - Characterization of thermal desorption with the Deans-switch technique in gas
chromatographic analysis of volatile organic compounds.
AB - This study presents a novel application based on the Deans-switch cutting
technique to characterize the thermal-desorption (TD) properties for gas
chromatographic (GC) analysis of ambient volatile organic compounds (VOCs). Flash
heating of the sorbent bed at high temperatures to desorb trapped VOCs to GC may
easily produce severe asymmetric or tailing GC peaks affecting resolution and
sensitivity if care is not taken to optimize the TD conditions. The TD peak
without GC separation was first examined for the quality of the TD peak by
analyzing a standard gas mixture from C2 to C12 at ppb level. The Deans switch
was later applied in two different stages. First, it was used to cut the trailing
tail of the TD peak, which, although significantly improved the GC peak symmetry,
led to more loss of the higher boiling compounds than the low boiling ones, thus
suggesting compound discrimination. Subsequently, the Deans switch was used to
dissect the TD peak into six 30s slices in series, and an uneven distribution in
composition between the slices were found. A progressive decrease in low boiling
compounds and increase in higher boiling ones across the slices indicated severe
inhomogeneity in the TD profile. This finding provided a clear evidence to answer
the discrimination problem found with the tail cutting approach to improve peak
symmetry. Through the use of the innovated slicing method based on the Deans
switch cutting technique, optimization of TD injection for highly resolved,
symmetric and non-discriminated GC peaks can now be more quantitatively assessed
and guided.
PMID- 27492598
TI - Electrical field assisted matrix solid phase dispersion as a powerful tool to
improve the extraction efficiency and clean-up of fluoroquinolones in bovine
milk.
AB - This work presents a new method by electrical matrix solid phase dispersion for
the extraction and clean-up of marbofloxacin, ofloxacin, norfloxacin,
ciprofloxacin, enrofloxacin, difloxacin and sarafloxacin in bovine milk.
Composition and pH of the eluent, applied electrical potential and polarity were
optimized by experimental designs. The combination of the chromatographic and
electrophoretic mechanisms allowed the extraction and clean-up in one step with
low organic solvent consumption, high extraction throughput and elution
automation. Linearity, precision, trueness and limit of quantification were
evaluated and provided values in accordance with other methods recently developed
for the analysis of fluoroquinolones in milk. This technique proved to be
promising for the extraction and clean-up of ionizable analytes in different milk
matrices.
PMID- 27492599
TI - Theoretical study of closed-loop recycling liquid-liquid chromatography and
experimental verification of the theory.
AB - The non-ideal recycling equilibrium-cell model including the effects of extra
column dispersion is used to simulate and analyze closed-loop recycling counter
current chromatography (CLR CCC). Previously, the operating scheme with the
detector located before the column was considered. In this study, analysis of the
process is carried out for a more realistic and practical scheme with the
detector located immediately after the column. Peak equation for individual
cycles and equations describing the transport of single peaks and complex
chromatograms inside the recycling closed-loop, as well as equations for the
resolution between single solute peaks of the neighboring cycles, for the
resolution of peaks in the recycling chromatogram and for the resolution between
the chromatograms of the neighboring cycles are presented. It is shown that,
unlike conventional chromatography, increasing of the extra-column volume (the
recycling line length) may allow a better separation of the components in CLR
chromatography. For the experimental verification of the theory, aspirin,
caffeine, coumarin and the solvent system hexane/ethyl acetate/ethanol/water
(1:1:1:1) were used. Comparison of experimental and simulated processes of
recycling and distribution of the solutes in the closed-loop demonstrated a good
agreement between theory and experiment.
PMID- 27492600
TI - Analysis of 4-bromo-3-fluorobenzaldehyde and separation of its regioisomers by
one-dimensional and two-dimensional gas chromatography.
AB - A starting material, 4-bromo-3-fluorobenzaldehyde, was used for active drug
substance (API) AMG 369 production. The presence of the regioisomer impurities in
the starting material 4-bromo-3-fluorobenzaldehyde presented significant
challenges for the API synthetic route development due to the physical-chemical
similarities of the impurities. These impurities significantly impact on the
purity of the starting-material and final drug substance. Control of these
impurities is important due to the potential genotoxicity of these impurities (p
GTI). Analytical development was carried out to develop GC methods with high
resolving power and high sensitivity to quantify the regioisomers presented in
starting material and therefore to control the purity of the starting material
and the final drug substance. In the study, complete resolution of the ten
regioisomers by 1D-GC and heart-cutting two-dimensional GC (2D-GC) was achieved.
A sensitive GC/micro electron capture detection (MU-ECD) method with high
resolving power and sensitivity to fully resolve all the ten regioisomers of 4
bromo-3-fluorobenzaldehyde was obtained by using a CHIRALDEX GC column (1D- GC).
To facilitate the systematic GC method development, heart-cutting two-dimensional
gas chromatography (2D-GC) using a Deans switch was exploited for the separation
of the ten regioisomers. The resulting heart-cutting 2D-GC method successfully
separated all the ten regioisomers with better sensitivity and resolution.
Regioisomer impurities in the starting material were identified and quantified by
these GC methods. The sensitivity for the methods is in the range of 0.004ng to
0.02ng for the regioisomers. Linearity for the methods is: R(2)=0.999 to 1.000.
The methods were suitable for control of the regioisomer impurities, p-GTIs, in
the starting material and final drug substance.
PMID- 27492601
TI - Neural correlates of olfactory and visual memory performance in 3D-simulated
mazes after intranasal insulin application.
AB - This fMRI study intended to establish 3D-simulated mazes with olfactory and
visual cues and examine the effect of intranasally applied insulin on memory
performance in healthy subjects. The effect of insulin on hippocampus-dependent
brain activation was explored using a double-blind and placebo-controlled design.
Following intranasal administration of either insulin (40IU) or placebo, 16 male
subjects participated in two experimental MRI sessions with olfactory and visual
mazes. Each maze included two separate runs. The first was an encoding maze
during which subjects learned eight olfactory or eight visual cues at different
target locations. The second was a recall maze during which subjects were asked
to remember the target cues at spatial locations. For eleven included subjects in
the fMRI analysis we were able to validate brain activation for odor perception
and visuospatial tasks. However, we did not observe an enhancement of declarative
memory performance in our behavioral data or hippocampal activity in response to
insulin application in the fMRI analysis. It is therefore possible that
intranasal insulin application is sensitive to the methodological variations e.g.
timing of task execution and dose of application. Findings from this study
suggest that our method of 3D-simulated mazes is feasible for studying neural
correlates of olfactory and visual memory performance.
PMID- 27492602
TI - Quality and Outcomes Framework: what have we learnt?
PMID- 27492603
TI - Heavy-metal contamination and solid-phase fractionation in street dust.
AB - Fourteen street-dust samples were collected from Hamedan, western Iran. Street
dust samples received different amounts of heavy-metal pollution. The samples
were analyzed for total cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and
zinc (Zn), and binding forms of heavy metal were determined in five fractions.
The results showed Cd was the only metal present appreciably, 25.21% and 25.92%,
in the exchangeable and carbonates fractions, respectively, and Cu was the only
metal predominantly associated, 31.77%, with organic fraction. Zn, 45.84%, was
present mainly in the Fe-Mn oxide fraction, and the residual fraction was the
most dominant solid phase pool of Ni and Pb, respectively, with 42.56% and
41.31%. The order of apparent mobility and potential metal bioavailability for
these contaminated street-dust samples is Cd > Zn > Cu > Pb > Ni. The risk
assessment code results showed very high risk for Cd; medium risk for Cu, Pb, and
Zn; and low risk for Ni.
PMID- 27492605
TI - Hydrogen bonds in methane-water clusters.
AB - Characterization of hydrogen bonds in CH4-(H2O)12 clusters was carried out by
using several quantum chemistry tools. An initial stochastic search provided
around 2 500 000 candidate structures, then, using a convex-hull polygon
criterion followed by gradient based optimization under the Kohn-Sham scheme, a
total of 54 well defined local minima were located in the Potential Energy
Surface. These structures were further analyzed through second-order many-body
perturbation theory with an extended basis set at the MP2/6-311++G(d,p) level.
Our analysis of Gibbs energies at several temperatures clearly suggests a
structural preference toward compact water clusters interacting with the external
methane molecule, instead of the more commonly known clathrate-like structures.
This study shows that CH4-(H2O)12 clusters may be detected at temperatures up to
179 K, this finding provides strong support to a recently postulated hypothesis
that suggests that methane-water clusters could be present in Mars at these
conditions. Interestingly, we found that water to water hydrogen bonding is
strengthened in the mixed clusters when compared to the isolated water dimer,
which in turn leads to a weakening of the methane to water hydrogen bonding when
compared to the CH4-(H2O) dimer. Finally, our evidence places a stern warning
about the abilities of popular geometrical criteria to determine the existence of
hydrogen bonds.
PMID- 27492604
TI - Depletion of Dicer promotes epithelial ovarian cancer progression by elevating
PDIA3 expression.
AB - Dicer is an essential component of the microRNA (miRNA) processing machinery
whose low expression is associated with advanced stage and poor clinical outcome
in epithelial ovarian cancer. To investigate the functional relevance of Dicer in
epithelial ovarian cancer and to identify its downstream effectors, two
dimensional gel electrophoresis combined with mass spectrometry was used for
proteomic profiling. Dicer depletion promoted ovarian cancer cell proliferation
and migration accompanied by a global upregulation of proteins. Twenty-six
proteins, 7 upregulated and 19 downregulated, were identified. The functions of
the identified proteins and their interactions were bioinformatically analyzed.
Among them, protein disulfide-isomerase A3 (PDIA3) was considered to be a
potential target protein of Dicer. PDIA3 repression by siRNA could significantly
relieve the proliferation- and migration-promoting effect mediated by Dicer
depletion in vitro and in vivo. Moreover, the miRNAs targeting PDIA3 were
decreased in cells with Dicer depletion. In summary, low Dicer expression
contributes to epithelial ovarian cancer progression by elevating PDIA3
expression.
PMID- 27492606
TI - Expectations of younger patients concerning activities after knee arthroplasty:
are we asking the right questions?
AB - PURPOSE: Indications for total and unicondylar knee arthroplasty (KA) have
expanded to younger patients, in which Patient-Reported Outcome Measures (PROMs)
often show ceiling effects. This might be due to higher expectations. Our aims
were to explore expectations of younger patients concerning activities in daily
life, work and leisure time after KA and to assess to what extent PROMs meet and
evaluate these activities of importance. METHODS: Focus groups were performed
among osteoarthritis (OA) patients <65 years awaiting KA, in which they indicated
what activities they expected to perform better in daily life, work and leisure
time after KA. Additionally, 28 activities of daily life, 17 of work and 27 of
leisure time were depicted from seven PROMS, which were rated on importance,
frequency and bother. A total score, representing motivation for surgery, was
also calculated. RESULTS: Data saturation was reached after six focus groups
including 37 patients. Younger OA patients expect to perform better on 16
activities after KA, including high-impact leisure time activities. From the
PROMs, daily life and work activities were rated high in both importance and
motivation for surgery, but for leisure time activities importance varied highly
between patients. All seven PROMs score activities of importance, but no single
PROM incorporates all activities rated important. CONCLUSION: Younger patients
expect to perform better on many activities of daily life, work and leisure time
after KA, and often at demanding levels. To measure outcomes of younger patients,
we suggest using PROMs that include work and leisure time activities besides
daily life activities, in which preferably scored activities can be
individualized.
PMID- 27492608
TI - Synthesis and Spectroscopic Investigation of Diketopyrrolopyrrole - Spiropyran
Dyad for Fluorescent Switch Application.
AB - We report the synthesis and characterization of a new fluorescent dyad SP-DPP
SP(9) via efficient palladium-catalyzed Sonogashira coupling of prop-2-yn-1-yl 3
(3',3'dimethyl-6-nitrospiro[chromene-2,2'-indolin]-1'-yl)propanoatespiropyran,
SP(8), a well known photochromic accepter, with 3,6-bis(5-bromothiophen-2-yl)-2,5
bis((R)-2-ethylhexyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione, DPP(4), a
highly fluorescent donor. Under visible light exposure the SP unit is in a closed
hydrophobic form, whereas under UV irradiation it converts to a polar,
hydrophilic open form named Merocyanine (MC), which is responsible for
functioning of photo-switch application. The photochemistry pertaining to
fluorescence switch, 'on/off' behaviour, of model dyad SP-DPP-SP(9) is
experimentally analyzed in solution as well as in solid state in polymer matrices
by photoluminescence(PL) and absorption spectroscopy. After absorption of UV
light the spiropyran unit of the dyad under goes the rupture of the spiro C-O
bond leading to the formation of MC. The absorption band of MC fairly overlaps to
the fluorescence of DPP unit resulting quenching of fluorescence via fluorescence
resonance energy transfer from exited DPP unit to ground state MC. In contrary,
the fluorescence of DPP is fully regained upon transformation of MC to SP by
exposure to visible light or thermal stimuli. Hence, the fluorescence intensity
of dyad 9 is regulated by reversible conversion among the two states of the
photochromic spiropyran units and the fluorescence resonance energy transfer
(FRET) between the MC form of SP and the DPP unit. Conversely, these scrutiny of
the experiment express that the design of dyad 9 is viable as efficient
fluorescent switch molecule in many probable commercial applications, such as,
logic gates and photonic and optical communications.
PMID- 27492607
TI - Defective DNA repair and chromatin organization in patients with quiescent
systemic lupus erythematosus.
AB - BACKGROUND: Excessive autoantibody production characterizing systemic lupus
erythematosus (SLE) occurs irrespective of the disease's clinical status and is
linked to increased lymphocyte apoptosis. Herein, we tested the hypothesis that
defective DNA damage repair contributes to increased apoptosis in SLE. METHODS:
We evaluated nucleotide excision repair at the N-ras locus, DNA double-strand
breaks repair and apoptosis rates in peripheral blood mononuclear cells from anti
dsDNA autoantibody-positive patients (six with quiescent disease and six with
proliferative nephritis) and matched healthy controls following ex vivo treatment
with melphalan. Chromatin organization and expression levels of DNA repair- and
apoptosis-associated genes were also studied in quiescent SLE. RESULTS: Defective
nucleotide excision repair and DNA double-strand breaks repair were found in SLE,
with lupus nephritis patients showing higher DNA damage levels than those with
quiescent disease. Melphalan-induced apoptosis rates were higher in SLE than
control cells and correlated inversely with DNA repair efficiency. Chromatin at
the N-ras locus was more condensed in SLE than controls, while treatment with the
histone deacetylase inhibitor vorinostat resulted in hyperacetylation of histone
H4, chromatin decondensation, amelioration of DNA repair efficiency and decreased
apoptosis. Accordingly, genes involved in DNA damage repair and signaling
pathways, such as DDB1, ERCC2, XPA, XPC, MRE11A, RAD50, PARP1, MLH1, MLH3, and
ATM were significantly underexpressed in SLE versus controls, whereas PPP1R15A,
BARD1 and BBC3 genes implicated in apoptosis were significantly overexpressed.
CONCLUSIONS: Epigenetically regulated functional abnormalities of DNA repair
machinery occur in SLE, regardless of clinical disease activity, and may promote
lymphocyte apoptosis. Approaches to correct these abnormalities may be of
therapeutic value in SLE.
PMID- 27492609
TI - Effect of pi-Extended Substituents on Photophysical Properties of BODIPY Dyes in
Solutions.
AB - Four boron-dipyrrine (BODIPY) based dyes with pi-extended substituents in 8
position of dipyrrin ligand have been synthesized and characterized.
Photophysical properties of the obtained compounds have been investigated in
different individual solvents. Deposits of solvent polarity and viscosity were
evaluated. BODIPY with 8-biphenyl substituent was found to be the fluorescent
molecular rotor in contrast to more extended substituents. The complex nature of
solvent-solute interactions leads to the poor applicability of standard
multiparameter approaches to BODIPY solvatochromic properties. Fluorescence
intensity was found to increase in case of solvent polarity growth, it is not
typical for BODIPY. Taking that into account the BODIPY with pi-extended
substituents could be used for fluorescence viscosity measurements, and as the
fluorescent media polarity indicators in analytical chemistry and biochemistry.
PMID- 27492610
TI - High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical
BCG Shortage.
AB - Bladder cancer is the second commonest urinary tract malignancy with 70-80 %
being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC
(T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at
greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin
(BCG) is commonly used as first line therapy in this patient group but there is a
current worldwide shortage. BCG has been shown to reduce recurrence in high-risk
NMIBC and is more effective that other intravesical agents including mitomycin C,
epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high
change of cure in this cohort (80-90 %) and is a more radical treatment option
which patients need to be counselled carefully about. Bladder thermotherapy and
electromotive drug administration with mitomycin C are alternative therapies with
promising short-term results although long-term follow-up data are lacking.
PMID- 27492612
TI - Unemployment and mental health.
PMID- 27492611
TI - ACVR1-Fc suppresses BMP signaling and chondro-osseous differentiation in an in
vitro model of Fibrodysplasia ossificans progressiva.
AB - Fibrodysplasia ossificans progressiva (FOP) is a rare and devastating genetic
disease of heterotopic endochondral ossification (HEO), and currently no
effective therapies are available for this disease. A recurrent causative
heterozygous mutation (c.617 G>A; R206H) for FOP was identified in activin
receptor type IA (ACVR1), a bone morphogenetic protein (BMP) type I receptor.
This mutation aberrantly activates the BMP-Smad1/5/8 signaling pathway and leads
to HEO in FOP patients. Here we report development of a soluble recombinant ACVR1
Fc fusion protein by combining the extracellular domain of human wild type ACVR1
and the Fc portion of human immunoglobulin gamma 1 (IgG1). The ACVR1-Fc fusion
protein significantly down-regulated the dysregulated BMP signaling caused by the
FOP ACVR1 mutation and effectively suppressed chondro-osseous differentiation in
a previously described cellular FOP model, human umbilical vein endothelial cells
(HUVECs) that were infected with adenovirus-ACVR1R206H (HUVECR206H). This ACVR1
Fc fusion protein holds great promise for prevention and treatment of HEO in FOP
and related diseases.
PMID- 27492613
TI - [Not Available].
PMID- 27492614
TI - Associations Between Health and Driving in an Older Adult Cohort in Rancho
Bernardo.
AB - OBJECTIVE: The purpose of this study was to identify the associations between
health and health care utilization with driving patterns in a cohort of older
adults. METHOD: In 2012, a total of 1,826 surviving participants in the Rancho
Bernardo cohort were sent a health and driving pattern survey; 1,277 were
returned. RESULTS: The majority of the respondents (1,151, 91%) were still
driving. Older age, female sex, hospitalizations, emergency department (ED)
visits and physical therapy visits, neurological disease, depression, limited
vision, and limited hearing were associated with non-driving status. A total of
809 (71%) of drivers reported no citations or crashes in the last 5 years.
DISCUSSION: The vast majority of older drivers in this cohort continued to drive,
and did so safely. Health care utilization, medications, medical conditions, and
self-assessment of health were associated with non-driving status. Prospective
studies are needed to clarify the temporal relationships between these factors.
PMID- 27492615
TI - A Survey of the Job Profiles of Biomedical Informatics Graduates.
AB - BACKGROUND: In 2003, the University of Sao Paulo established the first Biomedical
Informatics (BMI) undergraduate course in Brazil. Our mission is to provide
undergraduate students with formal education on the fundamentals of BMI and its
applied methods. This undergraduate course offers theoretical aspects, practical
knowledge and scientifically oriented skills in the area of BMI, enab- ling
students to contribute to research and methodical development in BMI. Course
coordinators, professors and students frequently evaluate the BMI course and the
curriculum to ensure that alumni receive quality higher education. OBJECTIVES:
This study investigates (i) the main job activities undertake by USP BMI
graduates, (ii) subjects that are fundamental important for graduates to pursue a
career in BMI, and (iii) the course quality perceived by the alumni. METHODS: Use
of a structured questionnaire to conduct a survey involving all the BMI graduates
who received their Bachelor degree before July, 2015 (attempted n = 205).
RESULTS: One hundred and forty-five graduates (71 %) answered the questionnaire.
Nine out of ten of our former students currently work as informaticians. Seventy
six graduates (52 %) work within the biomedical informatics field. Fifty-five
graduates (38 %) work outside the biomedical informatics field, but they work in
other IT areas. Ten graduates (7 %) do not work with BMI or any other informatics
activities, and four (3 %) are presently unemployed. Among the 145 surveyed BMI
graduates, 46 (32 %) and seven (5 %) hold a Master's degree and a PhD degree,
respectively. Database Systems, Software Engineering, Introduction to Computer
Science, Object-Oriented Programming, and Data Structures are regarded as the
most important subjects during the higher education course. The majority of the
graduates (105 or 72 %) are satisfied with the BMI education and training they
received during the undergraduate course. CONCLUSIONS: More than half of the
graduates from our BMI course work in their primary education area. Besides
technical adequacy, the diverse job profiles, and the high level of satisfaction
of our graduates indicate the importance of undergraduate courses specialized in
the BMI domain are of utmost importance.
PMID- 27492618
TI - Evaluation of a Laughter-based Exercise Program on Health and Self-efficacy for
Exercise.
AB - Background: Despite health benefits of physical activity (PA) and risks of
physical inactivity, many older adults do not accumulate sufficient levels of PA
to achieve associated health benefits. Lack of PA enjoyment may be a barrier to
PA participation. Combining simulated laughter and PA for strength, balance, and
flexibility is a potential solution for helping older adults maintain
independence in activities of daily living through enjoyable participation in PA.
Purpose of the study: The purpose of this study is to assess whether combining
simulated laughter exercises with a moderate-intensity strength, balance, and
flexibility PA program (i.e., LaughActive) increases participation in PA, health,
and self-efficacy for PA among older adults residing in 4 assisted living
facilities (ALFs). Design and methods: The 12-week wait list control pilot study
used pre- and 6-week post-intervention comparisons within and between groups
identified by paired sample t-test results among those who participated in twice
weekly LaughActive classes (n = 27). Results: Significant improvements (p < .05
.10) were observed in mental health (SF-36v2), aerobic endurance (2-minute step
test), and self-efficacy for exercise (OEE). Implications: PA programs that
elicit positive emotions through simulated laughter have the potential to improve
health, physical performance, and self-efficacy for PA among older adults and may
positively influence participant adherence.
PMID- 27492616
TI - Alcohol Consumption and Multiple Dysplastic Lesions Increase Risk of Squamous
Cell Carcinoma in the Esophagus, Head, and Neck.
AB - BACKGROUND & AIMS: Some patients develop multiple squamous cell carcinomas (SCCs)
in the upper aerodigestive tract, attributed to field cancerization; alcohol
consumption has been associated with this process. We examined the association
between multiple areas of dysplastic squamous epithelium with the development of
SCC of the esophagus or head and neck cancer, as well as alcohol consumption and
smoking. METHODS: We examined 331 patients with early stage esophageal SCC using
Lugol chromoendoscopy to evaluate the dysplastic squamous epithelium in the
esophagus. Patients then were assigned to 3 groups, based on the number of Lugol
voiding lesions: A, no lesion; B, 1-9 lesions; or C, 10 or more lesions.
Participants completed lifestyle surveys on their history of drinking, smoking,
and diet. All participants were evaluated by laryngopharyngoscopy before
registration; only those without head and neck cancer were included, except for
patients with superficial SCC limited to the subepithelial layer. Lesions
detected in the esophagus and head and neck by surveillance were considered to be
metachronous. The study end point was the cumulative incidence of metachronous
SCCs in the esophagus and head and neck after endoscopic resection of esophageal
SCC, according to the grade of Lugol-voiding lesions. At study entry, all
patients were instructed to abstain from alcohol and smoking. RESULTS: Over the 2
year study period, metachronous SCCs of the esophagus were detected in 4% of
patients in group A, in 9.4% of patients in group B, and in 24.7% of patients in
group C (P < .0001 for patients in group A vs B or B vs C). Head and neck SCCs
were detected in none of the patients in group A, in 1.7% of the patients in
group B, and in 8.6% of the patients in group C (P = .016 for patients in group A
vs C and P = .008 for patients in group B vs C). SCC of the esophagus or head and
neck developed in 4.0% of patients in group A, in 10.0% of patients in group B,
and in 31.4% of patients in group C (P < .0001 for group A vs B or A vs C).
Alcohol abstinence decreased the risk of multiple SCCs of the esophagus (adjusted
hazard ratio, 0.47, 95% confidence interval, 0.25-0.91; P = .025), whereas
smoking abstinence did not. CONCLUSIONS: Multiple dysplastic lesions in the
esophagus increase the risk of multiple SCCs. Alcohol abstinence reduces the risk
of metachronous SCCs. Clinical Trials registry: UMIN000001676 and UMIN000005466.
PMID- 27492619
TI - Confidant Availability (In)Stability and Emotional Well-Being in Older Men and
Women.
AB - Purpose of the study: The present study examined the role of stability and change
in the availability of a family member and a friend as a confidant in older
adults' emotional well-being. Method: Participants in two waves of the Wisconsin
Longitudinal Study (N = 4,631; M = 64.3, 53.7% female) were assessed on
depressive symptoms and the availability of a family member and friend as
confidant. Using mixed linear effects models, four groups were compared over time
and across gender on depressive symptoms: those with and without a family/friend
confidant at both waves and those who lost and gained a family/friend confidant.
Results: Those with stable availability of a family or friend confidant
consistently scored the lowest on depressive symptoms; the gain of a family or
friend confidant corresponded with a decrease in depressive symptoms, with a
larger effect seen for the gain of a family confidant; the loss of a family
confidant was associated with an increase in depressive symptoms over time; and
stable availability of a family or friend confidant was more strongly linked to
lower levels of depressive symptoms among women, whereas stable unavailability of
a family confidant was linked to higher levels of depressive symptoms.
Implications: Stable availability of either a family or friend confidant in late
life is especially salient to emotional well-being, notably among women.
Emotional well-being benefits from the gain of a confidant highlight the
importance of supplementing or substituting a loss, especially of a family
confidant, which is associated with a significant increase in depressive
symptoms.
PMID- 27492617
TI - A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and
Human Gut Microbiome Composition.
AB - BACKGROUND & AIMS: Genome-wide association studies have identified 200
inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's
disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed
to identify novel associations between IBD and functional genetic variants using
the Illumina ExomeChip (San Diego, CA). METHODS: Genotyping was performed in
10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single
nucleotide polymorphism loci in coding regions analyzed. A novel identified
association was replicated further in 2 independent cohorts. We further examined
the association of the identified single-nucleotide polymorphism with microbiota
from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured
using 16S sequencing. RESULTS: We identified an association between CD and a
missense variant encoding alanine or threonine at position 391 in the zinc
transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391
threonine, rs13107325) and replicated the association with CD in 2 replication
cohorts (combined meta-analysis P = 5.55 * 10(-13)). This variant has been
associated previously with distinct phenotypes including obesity, lipid levels,
blood pressure, and schizophrenia. We subsequently determined that the CD risk
allele was associated with altered colonic mucosal microbiome composition in both
healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted
in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24
* 10(-16)) and overweight individuals (P = 6.73 * 10(-16)). CONCLUSIONS: Our
results suggest that an SLC39A8-dependent shift in the gut microbiome could
explain its pleiotropic effects on multiple complex diseases including CD.
PMID- 27492621
TI - Sec16 alternative splicing dynamically controls COPII transport efficiency.
AB - The transport of secretory proteins from the endoplasmic reticulum (ER) to the
Golgi depends on COPII-coated vesicles. While the basic principles of the COPII
machinery have been identified, it remains largely unknown how COPII transport is
regulated to accommodate tissue- or activation-specific differences in cargo load
and identity. Here we show that activation-induced alternative splicing of Sec16
controls adaptation of COPII transport to increased secretory cargo upon T-cell
activation. Using splice-site blocking morpholinos and CRISPR/Cas9-mediated
genome engineering, we show that the number of ER exit sites, COPII dynamics and
transport efficiency depend on Sec16 alternative splicing. As the mechanistic
basis, we suggest the C-terminal Sec16 domain to be a splicing-controlled protein
interaction platform, with individual isoforms showing differential abilities to
recruit COPII components. Our work connects the COPII pathway with alternative
splicing, adding a new regulatory layer to protein secretion and its adaptation
to changing cellular environments.
PMID- 27492622
TI - In vitro acute and developmental neurotoxicity screening: an overview of cellular
platforms and high-throughput technical possibilities.
AB - Neurotoxicity and developmental neurotoxicity are important issues of chemical
hazard assessment. Since the interpretation of animal data and their
extrapolation to man is challenging, and the amount of substances with
information gaps exceeds present animal testing capacities, there is a big demand
for in vitro tests to provide initial information and to prioritize for further
evaluation. During the last decade, many in vitro tests emerged. These are based
on animal cells, human tumour cell lines, primary cells, immortalized cell lines,
embryonic stem cells, or induced pluripotent stem cells. They differ in their
read-outs and range from simple viability assays to complex functional endpoints
such as neural crest cell migration. Monitoring of toxicological effects on
differentiation often requires multiomics approaches, while the acute disturbance
of neuronal functions may be analysed by assessing electrophysiological features.
Extrapolation from in vitro data to humans requires a deep understanding of the
test system biology, of the endpoints used, and of the applicability domains of
the tests. Moreover, it is important that these be combined in the right way to
assess toxicity. Therefore, knowledge on the advantages and disadvantages of all
cellular platforms, endpoints, and analytical methods is essential when
establishing in vitro test systems for different aspects of neurotoxicity. The
elements of a test, and their evaluation, are discussed here in the context of
comprehensive prediction of potential hazardous effects of a compound. We
summarize the main cellular characteristics underlying neurotoxicity, present an
overview of cellular platforms and read-out combinations assessing distinct parts
of acute and developmental neurotoxicology, and highlight especially the use of
stem cell-based test systems to close gaps in the available battery of tests.
PMID- 27492620
TI - Physiological functions and clinical implications of the N-end rule pathway.
AB - The N-end rule pathway is a unique branch of the ubiquitin-proteasome system in
which the determination of a protein's half-life is dependent on its N-terminal
residue. The N-terminal residue serves as the degradation signal of a protein and
thus called N-degron. N-degron can be recognized and modifed by several steps of
post-translational modifications, such as oxidation, deamination, arginylation or
acetylation, it then polyubiquitinated by the N-recognin for degradation. The
molecular basis of the N-end rule pathway has been elucidated and its
physiological functions have been revealed in the past 30 years. This pathway is
involved in several biological aspects, including transcription, differentiation,
chromosomal segregation, genome stability, apoptosis, mitochondrial quality
control, cardiovascular development, neurogenesis, carcinogenesis, and
spermatogenesis. Disturbance of this pathway often causes the failure of these
processes, resulting in some human diseases. This review summarized the
physiological functions of the N-end rule pathway, introduced the related
biological processes and diseases, with an emphasis on the inner link between
this pathway and certain symptoms.
PMID- 27492623
TI - Pharmacokinetic and pharmacodynamics of xylazine administered to exercised
thoroughbred horses.
AB - There is limited data describing xylazine serum concentrations in the horse and
no reports of concentrations beyond 24 hours. The primary goal of the study
reported here was to update the pharmacokinetics of xylazine following
intravenous (IV) administration in order to assess the applicability of current
regulatory recommendations. Pharmacodynamic parameters were determined using PK
PD modeling. Sixteen exercised adult Thoroughbred horses received a single IV
dose of 200 mg of xylazine. Blood and urine samples were collected at time 0 and
at various times for up to 96 hours and analyzed using liquid chromatography
tandem mass spectrometry. Xylazine serum concentrations were best fit by a 3
compartment model. Mean +/- SEM systemic clearance, volume of distribution at
steady state, beta half-life and gamma half-life were 12.7 +/- 0.735 mL/min/kg,
0.660 +/- 0.053 L/kg, 2.79 +/- 0.105 hours and 26.0 +/- 1.9, respectively.
Immediately following administration, horses appeared sedate as noted by a
decrease in chin-to-ground distance, decreased locomotion and decreased heart
rate (HR). Sedation lasted approximately 45 minutes. Glucose concentrations were
elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1
and 325.7 ng/mL for HR, atrioventricular block, chin-to-ground distance and
glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute,
47.5%, 42.4 cm and 0.28 mg/dL for HR, atrioventricular block, chin-to-ground
distance and glucose concentrations, respectively. Pharmacokinetic parameters
differ from previous reports and a prolonged detection time suggests that an
extended withdrawal time, beyond current regulatory recommendations, is warranted
to avoid inadvertent positive regulatory findings in performance horses.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27492624
TI - Antidotal Effects of Curcumin Against Agents-Induced Cardiovascular Toxicity.
AB - Curcumin, the major phenolic compound in turmeric, shows preventive effects in
various diseases. Curcumin is commonly found in rhizome of the Curcuma species
and traditionally used in herbal medicine. Numeros studies has indicated that
curcumin posses protective effects against toxic agents in various systems
including cardiovascular. This study found that curcumin may be effective in
cardiovascular diseases induced by toxic agents including Streptozotocin,
Doxorubicin, Cyclosporin A, Methotrexate, Isoproterenol, Cadmium, Diesel exhaust
particle, Nicotine, Hydrogen peroxide, and tert- Butyl hydroperoxide. However,
due to the lake of information on human, further studies are needed to determine
the efficacy of curcumin as an antidote agent. The present study aimed to
critically review the recent literature data from that regarding the protective
effects of curcumin against agents-induced cardiovascular toxicity.
PMID- 27492625
TI - Introduction of nuclear medicine research in Japan.
AB - There were many interesting presentations of unique studies at the Annual Meeting
of the Japanese Society of Nuclear Medicine, although there were fewer attendees
from Europe than expected. These presentations included research on diseases that
are more frequent in Japan and Asia than in Europe, synthesis of original
radiopharmaceuticals, and development of imaging devices and methods with novel
ideas especially by Japanese manufacturers. In this review, we introduce recent
nuclear medicine research conducted in Japan in the five categories of Oncology,
Neurology, Cardiology, Radiopharmaceuticals and Technology. It is our hope that
this article will encourage the participation of researchers from all over the
world, in particular from Europe, in scientific meetings on nuclear medicine held
in Japan.
PMID- 27492626
TI - 2016 Young Investigators Meeting.
PMID- 27492627
TI - Morphofunctional alterations in the olivocochlear efferent system of the genetic
audiogenic seizure-prone hamster GASH:Sal.
AB - The genetic audiogenic seizure hamster (GASH:Sal) is a model of a form of reflex
epilepsy that is manifested as generalized tonic-clonic seizures induced by
external acoustic stimulation. The morphofunctional alterations in the auditory
system of the GASH:Sal that may contribute to seizure susceptibility have not
been thoroughly determined. In this study, we analyzed the olivocochlear efferent
system of the GASH:Sal from the organ of Corti, including outer and inner hair
cells, to the olivocochlear neurons, including shell, lateral, and medial
olivocochlear (LOC and MOC) neurons that innervate the cochlear receptor. To
achieve this, we carried out a multi-technical approach that combined auditory
hearing screenings, scanning electron microscopy, morphometric analysis of
labeled LOC and MOC neurons after unilateral Fluoro-Gold injections into the
cochlea, and 3D reconstruction of the lateral superior olive (LSO). Our results
showed that the GASH:Sal exhibited higher auditory brain response (ABR)
thresholds than their controls, as well as absence of distortion-product of
otoacoustic emissions (DPOAEs) in a wide range of frequencies. The ABR and DPOAE
results also showed differences between the left and right ears, indicating
asymmetrical hearing alterations in the GASH:Sal. These alterations in the
peripheral auditory activity correlated with morphological alterations. At the
cochlear level, the scanning electron microscopy analysis showed marked
distortions of the stereocilia from basal to apical cochlear turns in the
GASH:Sal, which were not observed in the control hamsters. At the brainstem
level, MOC, LOC, and shell neurons had reduced soma areas compared with control
animals. This LOC neuron shrinkage contributed to reduction in the LSO volume of
the GASH:Sal as shown in the 3D reconstruction analysis. Our study demonstrated
that the morphofunctional alterations of the olivocochlear efferent system are
innate components of the GASH:Sal, which might contribute to their susceptibility
to audiogenic seizures. This article is part of a Special Issue entitled "Genetic
and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models
to the Clinic".
PMID- 27492628
TI - Response to "Safety of repetitive transcranial magnetic stimulation in patients
with epilepsy: A systematic review" by Luisa Santos Pereira and colleagues.
PMID- 27492629
TI - Predictors of short-term mortality, cognitive and physical decline in older
adults in northwest Russia: a population-based prospective cohort study.
AB - BACKGROUND: The classical phenotype, accumulated deficit model and self-report
approach of frailty were found not useful in older adults in northwest Russia.
More research is needed to identify predictors of adverse outcomes in this
population. AIM: The aim of this study is to identify predictors of mortality,
autonomy and cognitive decline in a population that is characterized by a high
cardiovascular morbidity and mortality rate. METHODS: A population-based
prospective cohort study of 611 community-dwelling individuals 65+.
Anthropometry, medical history nutritional status were recorded. An evaluation of
cognitive, physical and autonomy function, spirometry, and laboratory tests were
performed. The total follow-up was 5 years. Multiple imputation, backward
stepwise Cox regression analysis, C-statistic, risk reclassification analysis and
the bootstrapping techniques were used to analyze the data. RESULTS: We found
that the combination of increasing age, male sex, low physical function, low mid
arm muscle area, low forced expiratory volume in 1 s and anemia was associated
with mortality for people 65+. The substitution of anemia with anemia + high
level of C-reactive protein (hCRP) and the addition of high brain natriuretic
peptide (hBNP) levels improved the classification of older persons at risk for
mortality. DISCUSSION/CONCLUSION: The combination of low physical function, low
mid-arm muscle area, low forced expiratory volume in 1 s, anemia with hCRP levels
and hBNP identified older persons at a higher risk for mortality. These
predictors may be used for the development of a prediction model to detect older
people who are at risk for adverse health outcomes in northwest Russia.
PMID- 27492631
TI - Motion Control of Micro-/Nanomotors.
AB - As we progress towards employing self-propelled micro-/nanomotors in envisioned
applications such as cargo delivery, environmental remediation, and therapeutic
treatments, precise control of the micro-/nanomotors direction and their speed is
essential. In this Review, major emerging approaches utilized for the motion
control of micro-/nanomotors have been discussed, together with the lastest
publications describing these approaches. Future studies could incorporate
investigations on micro-/nanomotors motion control in a real-world environment in
which matrix complexity might disrupt successful manipulation of these small
scale devices.
PMID- 27492630
TI - Modeling pollen time series using seasonal-trend decomposition procedure based on
LOESS smoothing.
AB - Analysis of airborne pollen concentrations provides valuable information on plant
phenology and is thus a useful tool in agriculture-for predicting harvests in
crops such as the olive and for deciding when to apply phytosanitary treatments
as well as in medicine and the environmental sciences. Variations in airborne
pollen concentrations, moreover, are indicators of changing plant life cycles. By
modeling pollen time series, we can not only identify the variables influencing
pollen levels but also predict future pollen concentrations. In this study,
airborne pollen time series were modeled using a seasonal-trend decomposition
procedure based on LOcally wEighted Scatterplot Smoothing (LOESS) smoothing
(STL). The data series-daily Poaceae pollen concentrations over the period 2006
2014-was broken up into seasonal and residual (stochastic) components. The
seasonal component was compared with data on Poaceae flowering phenology obtained
by field sampling. Residuals were fitted to a model generated from daily
temperature and rainfall values, and daily pollen concentrations, using partial
least squares regression (PLSR). This method was then applied to predict daily
pollen concentrations for 2014 (independent validation data) using results for
the seasonal component of the time series and estimates of the residual component
for the period 2006-2013. Correlation between predicted and observed values was r
= 0.79 (correlation coefficient) for the pre-peak period (i.e., the period prior
to the peak pollen concentration) and r = 0.63 for the post-peak period. Separate
analysis of each of the components of the pollen data series enables the sources
of variability to be identified more accurately than by analysis of the original
non-decomposed data series, and for this reason, this procedure has proved to be
a suitable technique for analyzing the main environmental factors influencing
airborne pollen concentrations.
PMID- 27492633
TI - Accurate application of a precontoured-locking plate for proximal humeral
fractures in Asians: a cadaveric study.
AB - OBJECTIVES: The purpose of this study was to identify the optimal position for a
precontoured-locking plating (PHILOS((r))) of the proximal humerus in Asians in
terms of conformity and to determine the prevalence of screw exits in the
position of the highest conformity. METHODS: Twenty adult humeri and 14 cadaveric
shoulders were included in this study. After placing the precontoured plate in
the well-fitted position on the humerus, we measured the distance between the
upper margin of the plate and the tip of greater tuberosity (GT) (distance A) and
the distance between the anterior margin of the plate and lateral border of the
bicipital groove (BG) (distance B). The prevalence of K-wire exits was assessed.
In the 14 cadaver shoulders, the mutual relation between the most inferior
locking sleeve of the optimally positioned plate and the axillary nerve was
evaluated to assess the potential for axillary nerve injury. RESULTS: The
precontoured plate was well-fitted and remained in a relatively constant position
in all specimens. Distance A was an average of 3.6 mm (range 1.4-5.5 mm), and
distance B was an average of 2.5 mm (range 0-4.6 mm). The K wire closest to the
BG pierced it in four cases (20 %), and most inferior K wires exited at an
average distance of 3.8 mm (range 1.6-9.0 mm) from the inferior articular margin
of the humeral head. Regarding involvement of the BG, articular width was the
only significant variable in the logistic regression model, with an odds' ratio
of 0.610. The axillary nerve was located at an average vertical distance of 59.7
mm (range 51.8-66.9 mm) from the tip of the GT in a vertically neutral position.
The results did not differ between the left and right sides (t = 0.326, p =
0.755). Although the axillary nerve was slightly inferior to the most inferior
locking holes of the proximal humerus, it was located in the path of their
locking sleeves on the deltoid muscle. CONCLUSION: The optimal position for the
highest conformity led to ideal fixation of the proximal humerus and inferomedial
support screw in Asians. However, the precontoured plate sometimes had screw
exits that involved the BG, and articular width had a large impact on involvement
of the BG. If locking sleeves for the most inferior holes were introduced on the
deltoid muscle in a neutral position, there was high potential for injury to the
axillary nerve in Koreans.
PMID- 27492632
TI - Voluntary exercise blocks Western diet-induced gene expression of the chemokines
CXCL10 and CCL2 in the prefrontal cortex.
AB - Obesity increases inflammation, both peripherally and centrally, and exercise can
ameliorate some of the negative health outcomes associated with obesity. Within
the brain, the effect of obesity on inflammation has been well characterized in
the hypothalamus and hippocampus, but has been relatively understudied in other
brain regions. The current study was designed to address two primary questions;
(1) whether western diet (high fat/high sucrose) consumption would increase
markers of inflammation in the prefrontal cortex and (2) whether concurrent
voluntary wheel running would ameliorate any inflammation. Adult male mice were
exposed to a western diet or a control diet for 8weeks. Concurrently, half the
animals were given running wheels in their home cages, while half did not have
access to wheels. At the conclusion of the study, prefrontal cortex was removed
and expression of 18 proinflammatory genes was assayed. Expression of a number of
proinflammatory molecules was upregulated by consumption of the western diet. For
two chemokines, chemokine (C-C motif) ligand 2 (CCL2) and C-X-C motif chemokine
10 (CXCL10), voluntary exercise blocked the increase in the expression of these
genes. Cluster analysis confirmed that the majority of the tested genes were
upregulated by western diet, and identified another small cluster of genes that
were downregulated by either diet or exercise. These data identify a
proinflammatory phenotype within the prefrontal cortex of mice fed a western
diet, and indicate that chemokine induction can be blocked by voluntary exercise.
PMID- 27492634
TI - Genetic associations with neuroendocrine tumor risk: results from a genome-wide
association study.
AB - The etiology of neuroendocrine tumors remains poorly defined. Although
neuroendocrine tumors are in some cases associated with inherited genetic
syndromes, such syndromes are rare. The majority of neuroendocrine tumors are
thought to be sporadic. We performed a genome-wide association study (GWAS) to
identify potential genetic risk factors for sporadic neuroendocrine tumors. Using
germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix
6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana
Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from
the Harvard School of Public Health. An additional 241 controls from Dana-Farber
Cancer Institute were used for quality control. We assessed risk associations in
the overall cohort, and in neuroendocrine tumor subgroups. We identified no
potential risk associations in the cohort overall. In the small intestine
neuroendocrine tumor subgroup, comprising 293 cases, we identified risk
associations with three SNPs on chromosome 12, all in strong LD. The three SNPs
are located upstream of ELK3, a transcription factor implicated in angiogenesis.
We did not identify clear risk associations in the bronchial or pancreatic
neuroendocrine subgroups. This large-scale study provides initial evidence that
presumed sporadic small intestine neuroendocrine tumors may have a genetic
etiology. Our results provide a basis for further exploring the role of genes
implicated in this analysis, and for replication studies to confirm the observed
associations. Additional studies to evaluate potential genetic risk factors for
sporadic pancreatic and bronchial neuroendocrine tumors are warranted.
PMID- 27492635
TI - PYK2 via S6K1 regulates the function of androgen receptors and the growth of
prostate cancer cells.
AB - Androgen receptor (AR) is a steroid hormone receptor that functions as a
transcription factor for regulating cell growth and survival. Aberrant AR
function becomes a risk factor for promoting the progression of prostate cancer
(PCa). In this study, we examined the roles of proline-rich tyrosine kinase 2
(PYK2) and ribosomal S6 kinase 1 (S6K1) in regulating AR expression and activity
and growth properties in PCa cells. Compared with normal prostate tissues, PCa
tumors exhibited high levels of PYK2 and S6K1 expression. Furthermore, the
expression levels of PYK2 and S6K1 were significantly correlated with nuclear AR
expression in PCa tissues. We further found the association between PYK2, S6K1,
and AR in their protein expression and phosphorylation levels among normal
prostate PZ-HPV-7 cells and prostate cancer LNCaP and 22Rv1 cells. Overexpression
of the wild-type PYK2 in PZ-HPV-7 and LNCaP cells promoted AR and S6K1 expression
and phosphorylation as well as enhanced cell growth. In contrast, expression of
the mutated PYK2 or knockdown of PYK2 expression in LNCaP or 22Rv1 cells caused
reduced expression or phosphorylation of AR and S6K1 as well as retarded cell
growth. Under an androgen-deprived condition, PYK2-promoted AR expression and
phosphorylation and PSA production in LNCaP cells can be abolished by knocking
down S6K1 expression. In summary, our data suggested that PYK2 via S6K1
activation modulated AR function and growth properties in PCa cells. Thus, PYK2
and S6K1 may potentially serve as therapeutic targets for PCa treatment.
PMID- 27492636
TI - Sleep Quality Predicts Persistence of Parental Postpartum Depressive Symptoms and
Transmission of Depressive Symptoms from Mothers to Fathers.
AB - BACKGROUND: Early parenthood is a time of chronic sleep disturbance and also of
heightened depression risk. Poor sleep quality has been identified both as a
predictor of postpartum depressive symptoms and as a consequence. PURPOSE: This
study sought to clarify causal pathways linking sleep and postpartum depression
via longitudinal path modeling. Sleep quality at 6 months postpartum was
hypothesized to exacerbate depressive symptoms from 1 month through 1 year
postpartum in both mothers and fathers. Within-couple associations between sleep
and depression were also tested. METHODS: Data were drawn from a low-income,
racially and ethnically diverse sample of 711 couples recruited after the birth
of a child. Depressive symptoms were assessed at 1, 6, and 12 months postpartum,
and sleep was assessed at 6 months postpartum. RESULTS: For both partnered
mothers and fathers and for single mothers, depressive symptoms at 1 month
postpartum predicted sleep quality at 6 months, which in turn predicted
depressive symptoms at both 6 and 12 months. Results held when infant birth
weight, breastfeeding status, and parents' race/ethnicity, poverty, education,
and immigration status were controlled. Mothers' and fathers' sleep quality and
depressive symptoms were correlated, and maternal sleep quality predicted
paternal depressive symptoms both at 6 and at 12 months. CONCLUSIONS: Postpartum
sleep difficulties may contribute to a vicious cycle between sleep and the
persistence of depression after the birth of a child. Sleep problems may also
contribute to the transmission of depression within a couple. Psychoeducation and
behavioral treatments to improve sleep may benefit new parents.
PMID- 27492637
TI - Incentivizing research into the effectiveness of medical devices.
PMID- 27492638
TI - In-vivo characterization of left-ventricle pressure-volume telemetry system in
swine model.
AB - We present in-vivo study related to the use of our implantable RF telemetry
system for pressure-volume (PV) cardiac monitoring in a animal subject. We
implant a commercial MEMS PV sensor into the subject's heart left-ventricle (LV),
while the telemetry system is implanted outside of the heart and connected to the
sensor with a 7-microwires tether. The RF telemetry system is suitable for
commercial application in medium sized subjects, its total volume of 2.475cm(3)
and a weight of 4.0g. Our designed system is 58 % smaller in volume, 44 % in
weight and has a 55 % reduction in sampling power over the last reported research
in PV telemetry. In-vivo data was captured in both an acute and a freely moving
setting over a 24 hour period. We experimentally demonstrated viability of the
methodology that includes the surgical procedure and real-time monitoring of the
in-vivo data in a freely moving subject. Further improvements in catheter design
will improve the data quality and safety of the subject. This real-time
implantable technology allows for researchers to quantify cardiac pathologies by
extracting real-time pressure-volume loops, wirelessly from within freely moving
subjects.
PMID- 27492639
TI - August 2016 at a glance: the new ESC guidelines, and pathophysiology,
epidemiology and prognosis of heart failure.
PMID- 27492640
TI - Novel models and mechanisms of heart failure with preserved ejection fraction.
PMID- 27492641
TI - Dose response characterization of the association of serum digoxin concentration
with mortality outcomes in the Digitalis Investigation Group trial.
AB - AIMS: Many patients with heart failure and reduced EF remain at high risk for
hospitalization despite evidence-based therapy. Digoxin may decrease
hospitalization; however, uncertainty persists concerning its proper
administration and effect on mortality. This study investigated whether using
dose response concepts to re-evaluate the relationship between serum digoxin
concentration and key mortality outcomes in patients with reduced EF in the
Digitalis Investigation Group trial would help clarify efficacy and safety.
METHODS AND RESULTS: Multivariable Cox proportional hazards modelling and
propensity score adjustment assessed the relationship between serum digoxin
concentration (>=0.5 ng/mL) as a continuous variable and mortality outcomes. In
patients treated with digoxin, a significant linear association was found between
serum concentration and all-cause mortality [adjusted hazard ratio (HR) 1.25, 95%
confidence interval (CI) 1.14-1.38, P < 0.001 per 0.5 ng/mL increase in serum
concentration]. Based on this relationship, a bidirectional association was found
between digoxin therapy and all-cause mortality when compared with placebo. The
lowest serum concentrations (0.5-0.7 ng/mL) were associated with the lowest risk
of all-cause mortality (adjusted HR 0.77, 95% CI 0.67-0.89, P < 0.001) while high
serum concentrations (1.6-2.0 ng/mL) were associated with increased mortality
(adjusted HR 1.33, 95% CI 1.12-1.58, P = 0.001). Consistent with this finding,
lower serum concentrations (0.5-0.7 ng/mL) were associated with reduced death
from worsening heart failure and a neutral effect on cardiovascular death not due
to worsening heart failure. CONCLUSION: These findings favour targeting serum
concentrations from 0.5 to 0.7 ng/mL when dosing digoxin in patients with heart
failure and reduced EF.
PMID- 27492642
TI - Targeting digoxin dosing to serum concentration: is the bullseye too small?
PMID- 27492643
TI - Practice audit of the role of the Non-medical surgical assistant in Australia, an
online survey.
AB - The term Non-Medical Surgical Assistant (NMSA) encompasses all roles where
healthcare clinicians without a medical degree provide clinical services during
the perioperative cycle. The role of NMSA is gaining momentum within Australia.
It is timely to ascertain who is preforming the role and quantify the practice
setting and scope of practice to enable a nationally recognised platform for role
evolution. For two months in 2015 a NMSA Practice Audit was available online.
Sampling was initially of a convenience modality. A total of 83 clinicians
responded. The majority of NMSAs were experienced RNs [>11yrs]; held post
graduate qualifications [80%], practiced predominantly in metropolitan areas
[65%] and had been performing the role for 8 years or less. The specialty with
the highest uptake of the NMSAs is orthopaedic surgery. This paper provides an
overview of NMSAs practicing in Australia and provides cost effective evidence of
the need for this service in Australian healthcare.
PMID- 27492644
TI - Reliability of the "Ten Test" for assessment of discriminative sensation in hand
trauma.
AB - "Ten Test" (TT) is a bedside measure of discriminative sensation, whereby the
magnitude of abnormal sensation to moving light touch is normalized to an area of
normal sensation on an 11-point Likert scale (0-10). The purposes of this study
were to determine reliability parameters of the TT in a cohort of patients
presenting to a hand trauma clinic with subjectively altered sensation post
injury and to compare the reliability of TT to that of the Weinstein Enhanced
Sensory Test (WEST). Study participants (n = 29, mean age = 37 +/- 12) comprised
patients presenting to an outpatient hand trauma clinic with recent hand trauma
and self reported abnormal sensation. Participants underwent TT and WEST by two
separate raters on the same day. Interrater reliability, response stability and
responsiveness of each test were determined by the intraclass correlation
coefficient (ICC: 2, 1), standard error of measurement (SEM) with 95% confidence
intervals (CI) and minimal detectable difference score, with 95% CI (MDD95),
respectively. The TT displayed excellent interrater reliability (ICC = 0.95, 95%
CI 0.89-0.97) compared to good reliability for WEST (ICC = 0.78, 95% CI 0.58
0.89). The range of true scores expected with 95% confidence based on the SEM
(i.e. response stability), was +/-1.1 for TT and +/-1.1 for WEST. MDD95 scores
reflecting test responsiveness were 1.5 and 1.6 for TT and WEST, respectively.
The TT displayed excellent reliability parameters in this patient population.
Reliability parameters were stronger for TT compared to WEST. These results
provide support for the use of TT as a component of the sensory exam in hand
trauma.
PMID- 27492645
TI - Identification of a fourth ancient member of the IL-3/IL-5/GM-CSF cytokine
family, KK34, in many mammals.
AB - The related cytokine genes IL-3, IL-5 and GM-CSF map to the (extended) TH2
cytokine locus of the mammalian genome. For chicken an additional related
cytokine gene, KK34, was reported downstream of the IL-3 plus GM-CSF cluster, but
hitherto it was believed that mammalian genomes lack this gene. However, the
present study identifies an intact orthologue of chicken KK34 gene in many
mammals like cattle and pig, while remnants of KK34 can be found in human and
mouse. Bovine KK34 was found to be transcribed, and its recombinant protein could
induce STAT5 phosphorylation and proliferation of lymphocytes upon incubation
with bovine PBMCs. This concludes that KK34 is a fourth functional cytokine of
the IL-3/IL-5/GM-CSF/KK34-family (alias IL-5 family) in mammals. While analyzing
KK34, the present study also made new identifications of cytokine genes in the
extended TH2 cytokine loci for reptiles, birds and marsupials. This includes a
hitherto unknown cytokine gene in birds and reptiles which we designated "IL
5famE". Other newly identified genes are KK34, GM-CSF(-like), IL-5, and IL-13 in
reptiles, and IL-3 in marsupials.
PMID- 27492646
TI - Molecular cloning of the rabbit interleukin 6 promoter: Functional
characterization of rabbit hemorrhagic disease virus response elements in RK-13
cells.
AB - Infection with rabbit hemorrhagic disease virus (RHDV) can cause acute liver
failure (ALF), leading to severe mortality in rabbits. Inflammatory response,
especially the expression of inflammatory cytokines such as interleukin (IL)
1beta, tumor necrosis factor (TNF)-alpha, and IL-6, may play major roles in
mediating and amplifying the ALF. Among these cytokines, IL-6 is a
multifunctional cytokine with a central role in various physiological
inflammatory and immunological processes. In this study, we found that RHDV
infection significantly upregulated IL-6 gene expression in vivo. Next, the
rabbit IL-6 promoter was cloned and analyzed. Transfection of full-length RHDV
cDNA in RK-13 cells upregulated the activity of the IL-6 promoter. A series of 5'
deletion constructs demonstrated that AP-1 (activator protein 1), NF-IL6 (nuclear
factor interleukin-6), and NF-kappaB (nuclear factor kappa B) elements were
critical for RHDV-induced IL-6 transcription. Besides, the CREB (cAMP-response
element binding protein) element may also play an accessory effect on RHDV
induced IL-6 transcription. Collectively, the results elucidate the mechanism of
IL-6 induction, and enrich the RHDV pathogenesis in rabbit.
PMID- 27492647
TI - Percutaneous Balloon Aortic Valvuloplasty and Clinical Outcomes in Severe Aortic
Stenosis: Correlation of Procedural Technique and Efficacy.
AB - BACKGROUND: Percutaneous balloon aortic valvuloplasty (PBAV) is a palliative
therapeutic option for relief of severe aortic stenosis (AS) in patients that are
poor surgical or transcatheter aortic valve replacement (TAVR) candidates or as a
bridge to definitive therapy. The outcomes following PBAV are highly variable and
studies identifying factors that correlate with outcomes are sparse. The purpose
of this study was to identify predictors at the time of the index procedures that
can predict 1-year survival or need for repeat PBAV. METHODS: Demographic and
procedural information of 505 PBAVs performed on 388 patients from January 1999
to December 2012 at the Deborah Heart and Lung Center were reviewed. Procedural
data were compared across many variables and outcomes to identify predictors of
outcomes. These predictors were statistically compared using chi-squared tests or
Student's t-test. RESULTS: Of the 388 patients analyzed, 145 (37.4%) expired
within 1 year following the index procedure. The cohort was then stratified into
3 groups based on the number of balloon inflations. They were similar with regard
to baseline characteristics. The mean age was 81.9 +/- 9 years. Males constituted
51% of the cohort. Patients who underwent 2 and 3+ inflations had a 47.6% and
93.0% increase in the postprocedural aortic valve area compared to patients who
had only 1 inflation. Patients who underwent 3+ inflations were significantly
less likely to require a repeat PABV within a year and the repeat procedure free
survival rate of 94.5% (P = 0.009). Despite improvement in valve area, there was
no statistically significant difference in 1 year mortality between the groups
(28.8% vs 42.9% vs 46.1% for 1 vs 2 vs 3+ inflations, respectively). CONCLUSIONS:
PBAV provides a modest improvement in valve function and continues to be a safe
and feasible option in experienced hands for select patients that are high risk
for surgery or TAVR. The use of additional inflations during PBAV resulted in
better long-term outcomes.
PMID- 27492648
TI - Validity and reliability of the Bristol Stool Form Scale in healthy adults and
patients with diarrhoea-predominant irritable bowel syndrome.
AB - BACKGROUND: The Bristol Stool Form Scale (BSFS) is a 7-point scale used
extensively in clinical practice and research for stool form measurement, which
has undergone limited validity and reliability testing. AIM: To determine the
validity and reliability of the BSFS in measuring stool form in healthy adults
and patients with diarrhoea-predominant irritable bowel syndrome (IBS-D).
METHODS: One hundred and sixty-nine healthy volunteers provided a stool sample
and used the BSFS to classify stool form, which was compared with measured stool
water content and with values from 19 patients with IBS-D. Eighty-six volunteers
used the BSFS to classify 26 stool models to determine accuracy and reliability.
RESULTS: Volunteers' classifications of stool type correlated with stool water
(Spearman's rho = 0.491, P < 0.001), which increased in hard (Types 1-2), normal
(Types 3-5) and loose stools (Types 6-7) (P < 0.001). The BSFS detected
differences in stool form between healthy volunteers (mean 3.7, s.d. 1.5) and IBS
D patients (mean 5.0, s.d. 1.2) (P < 0.001). Overall, 977/1204 (81%) stool models
were correctly classified (substantial accuracy, kappa = 0.78), although <80% of
Types 2, 3, 5 and 6 were classified correctly. On 852/1118 (76%) occasions,
volunteers classified covert duplicate models to the same stool type (substantial
reliability, kappa = 0.72), but with only moderate reliability for Types 2 (63%,
kappa = 0.57) and 3 (62%, kappa = 0.55). CONCLUSIONS: The BSFS demonstrated
substantial validity and reliability, although difficulties arose around clinical
decision points (Types 2, 3, 5, 6) that warrant investigation in larger clinical
populations. Potential for improving validity and reliability through
modifications to the BSFS or training in its use should be explored.
PMID- 27492649
TI - Mechanistic study of the radical SAM-dependent amine dehydrogenation reactions.
AB - The radical SAM enzyme NosL catalyzes the conversion of l-Trp to 3-methyl-2
indolic acid, and this reaction is initiated by the 5'-deoxyadenosyl (dAdo)
radical-mediated hydrogen abstraction from the l-Trp amino group. We demonstrate
here that when d-Trp was used in the NosL reaction, hydrogen abstraction occurs
promiscuously at both the amino group and Calpha of d-Trp. These results inspired
us to establish the detailed mechanism of l-Trp amine dehydrogenation catalyzed
by a NosL mutant, and to engineer a novel radical SAM-dependent l-Tyr amine
dehydrogenase from the thiamine biosynthesis enzyme ThiH.
PMID- 27492650
TI - A wide-necked extracranial internal carotid artery saccular aneurysm with
ipsilateral proximal compression.
AB - Extracranial internal carotid artery aneurysms (EICAA) are rare and can elicit
various neurologic symptoms. Here, we present a case of a saccular EICAA
compressing its proximal parent internal carotid artery (ICA). Ultrasonography
demonstrated the proximal ICA stenosis and the "tardus-parvus" Doppler waveform
downstream. The patient underwent aneurysmectomy and graft interposition. The
histologic analysis highly supported an atypical fibromuscular dysplasia.
Although this patient only showed a neck mass, the reduced ipsilateral cerebral
blood supply was a potential cause for neurologic symptoms. (c) 2016 Wiley
Periodicals, Inc. J Clin Ultrasound 45:116-120, 2017.
PMID- 27492651
TI - Novel Genetic, Clinical, and Pathomechanistic Insights into TFG-Associated
Hereditary Spastic Paraplegia.
AB - Hereditary spastic paraplegias (HSPs) are genetically and clinically
heterogeneous axonopathies primarily affecting upper motor neurons and, in
complex forms, additional neurons. Here, we report two families with distinct
recessive mutations in TFG, previously suggested to cause HSP based on findings
in a single small family with complex HSP. The first carried a homozygous
c.317G>A (p.R106H) variant and presented with pure HSP. The second carried the
same homozygous c.316C>T (p.R106C) variant previously reported and displayed a
similarly complex phenotype including optic atrophy. Haplotyping and bisulfate
sequencing revealed evidence for a c.316C>T founder allele, as well as for a
c.316_317 mutation hotspot. Expression of mutant TFG proteins in cultured neurons
revealed mitochondrial fragmentation, the extent of which correlated with
clinical severity. Our findings confirm the causal nature of bi-allelic TFG
mutations for HSP, broaden the clinical and mutational spectra, and suggest
mitochondrial impairment to represent a pathomechanistic link to other
neurodegenerative conditions.
PMID- 27492652
TI - Constructal approach to bio-engineering: the ocular anterior chamber temperature.
AB - The aim of this work was to analyse the pressure inside the eyes anterior
chamber, namedintraocular pressure (IOP), in relation to the biomechanical
properties of corneas. The approach used was based on the constructal law,
recently introduced in vision analysis. Results were expressed as the relation
between the temperature of the ocular anterior chamber and the biomechanical
properties of the cornea. The IOP, the elastic properties of the cornea, and the
related refractive properties of the eye were demonstrated to be dependent on the
temperature of the ocular anterior chamber. These results could lead to new
perspectives for experimental analysis of the IOP in relation to the properties
of the cornea.
PMID- 27492653
TI - Extracorporeal Membrane Oxygenation (ECMO) for Hypothermic Cardiac Deterioration:
A Case Series.
AB - Accidental hypothermia can lead to untoward cardiac manifestations and arrest.
This report presents a case series of severe accidental hypothermia with cardiac
complications in three emergency patients who were treated with extracorporeal
membrane oxygenation (ECMO) and survived after re-warming. The aim of this
discussion was to encourage more clinicians to consider ECMO as a re-warming
therapy for severe hypothermia with circulatory collapse and to prompt discussion
about decreasing the barriers to its use. Niehaus MT , Pechulis RM , Wu JK , Frei
S , Hong JJ , Sandhu RS , Greenberg MR . Extracorporeal membrane oxygenation
(ECMO) for hypothermic cardiac deterioration: a case series. Prehosp Disaster
Med. 2016;31(5):570-571.
PMID- 27492654
TI - In silico and in vivo stability analysis of a heterologous biosynthetic pathway
for 1,4-butanediol production in metabolically engineered E. coli.
AB - Recently, several approaches have been published in order to develop a functional
biosynthesis route for the non-natural compound 1,4-butanediol (BDO) in E. coli
using glucose as a sole carbon source or starting from xylose. Among these
studies, there was reported as high as 18 g/L product concentration achieved by
industrial strains, however BDO production varies greatly in case of the reviewed
studies. Our motivation was to build a simple heterologous pathway for this
compound in E. coli and to design an appropriate cellular chassis based on a
systemic biology approach, using constraint-based flux balance analysis and bi
level optimization for gene knock-out prediction. Thus, the present study
reports, at the "proof-of concept" level, our findings related to model-driven
development of a metabolically engineered E. coli strain lacking key genes for
ethanol, lactate and formate production (DeltapflB, DeltaldhA and DeltaadhE),
with a three-step biosynthetic pathway. We found this strain to produce a limited
quantity of 1,4-BDO (.89 mg/L BDO under microaerobic conditions and .82 mg/L
under anaerobic conditions). Using glycerol as carbon source, an approach, which
to our knowledge has not been tackled before, our results suggest that further
metabolic optimization is needed (gene-introductions or knock-outs, promoter fine
tuning) to address the redox potential imbalance problem and to achieve
development of an industrially sustainable strain. Our experimental data on
culture conditions, growth dynamics and fermentation parameters can consist a
base for ongoing research on gene expression profiles and genetic stability of
such metabolically engineered E. coli strains.
PMID- 27492655
TI - Differences between prolonged weaning patients from medical and surgical
intensive care units.
AB - BACKGROUND: It is not clear whether patients entering a specialized,
interdisciplinary weaning unit from surgical or medical intensive care units
(ICU) distinguish substantially. The purpose of the present study was to assess
differences in patients with prolonged weaning being referred from surgical and
medical ICU. METHODS: Data collected from April 2013 to April 2014 was conducted
for retrospective analysis. Mortality rates, demographic data, clinical, and
microbial differences in 150 patients with prolonged weaning were assessed (80
surgical and 70 medical). RESULTS: Surgical ICU referrals tended to be older
(70.7 +/- 11.3 vs. 67.3 +/- 12.3, P = 0.051) and had fewer underlying pulmonary
diseases (45% vs. 60%, P = 0.067). Sodium values at the time of referral to the
weaning unit were significantly higher in surgical (147.1 +/- 9.6) vs. medical
(141.3 +/- 6.7 mmol/l) patients (P < 0.001). Each 10-unit increase in sodium at
the time of referral to the weaning unit was associated with a 2.5-day (95% CI
0.4, 5.4; P = 0.09) prolongation of stay in the weaning unit. Although
significant differences in microbiological agents from tracheal aspiration were
seen, the infection rate on the weaning unit was similar in both groups. There
was no difference in weaning unit mortality between surgical and medical ICU
patients (18% vs. 23%; P = 0.41). CONCLUSION: Few differences were found between
patients being referred to a specialized weaning unit from surgical vs. medical
ICUs. Besides differences in microbiological characteristics of tracheal
secretions, there were also differences in sodium levels, which appear to
influence on treatment duration.
PMID- 27492656
TI - Using L-STM to directly visualize enzymatic self-assembly/disassembly of
nanofibers.
AB - Self-assembly/disassembly is ubiquitous in nature and plays an important role in
many biological events. But noninvasive characterization of this process in real
time at molecular resolution remains challenging. Herein, using homebuilt liquid
phase scanning tunneling microscopy (L-STM) with ultrahigh stability, we directly
visualized enzymatic self-assembly/disassembly of oligopeptide nanofibers in real
time for the first time. Static high-resolution L-STM images clearly showed the
molecular packing details in the supramolecular nanofiber and the diameter of the
nanofiber was consistent with that of cryo transmission electron microscopy (cryo
TEM) observations. Moreover, the self-repairing behavior of the supramolecular
nanofibers was also directly observed at high resolution for the first time. This
work unprecedentedly revealed new insights into Nature-mimic self-assembly and
disassembly at the molecular level. It also illustrates the potential of our
homebuilt L-STM in studying delicate biological processes in physiological
solution with high resolution.
PMID- 27492657
TI - Effects of long-term iloprost treatment on right ventricular function in patients
with Eisenmenger syndrome.
AB - BACKGROUND: Right ventricular (RV) function is an important prognostic factor of
pulmonary arterial hypertension (PAH), but there is insufficient data regarding
RV function after long-term inhaled iloprost treatment. We evaluated the effect
of long-term iloprost treatment on RV function in patients with Eisenmenger
syndrome (ES). METHODS: Eleven consecutive patients with ES associated with
congenital heart disease underwent echocardiographic measurements at baseline and
48 weeks after iloprost therapy. In addition, we recorded World Health
Organization (WHO) functional class, 6-minute walk distance (6MWD), systemic
arterial oxygen saturation (SaO2), and laboratory values such as hemoglobin,
serum creatinine, and N-terminal pro-B natriuretic peptide. RESULTS: After 48
weeks of iloprost therapy, mean pulmonary arterial pressure (mPAP), pulmonary
arterial systolic pressure (PASP), and pulmonary vascular resistance (PVR) were
significantly decreased [mPAP, 42.5 (38.5-61.0) to 36.5 (29.1-40.0)mmHg; PASP,
92.6+/-19.9 to 74.5+/-23.8mmHg; PVR, 23.4 (19.8-26.0) to 23.4 (19.8-26.0)Wood
unit respectively, all p<0.05]. There was also significant improvement in RV
myocardial performance index [0.68 (0.61-0.80) to 0.52 (0.51-0.62), p=0.003] and
RV longitudinal strain (-15.7+/-1.6 to -18.1+/-1.5%, p<0.001). In clinical
assessment, WHO functional class (p=0.006), 6MWD (310.6+/-44.7 to 399.7+/-80.8m,
p<0.001), and SaO2 (90.9+/-6.0% to 92.5+/-6.0%, p=0.022) were significantly
improved. CONCLUSION: The improvement in echocardiographic parameters of the RV
function after 48 weeks of iloprost therapy may provide insight on the efficacy
of long-term iloprost treatment for RV functional improvement, which is a
prognostic factor in patients with ES.
PMID- 27492658
TI - Is a bare-metal stent still useful for improving the outcome of percutaneous
coronary intervention? From the FU-Registry.
AB - BACKGROUND: Percutaneous coronary intervention (PCI) with a drug-eluting stent
(DES) is increasingly being used for the treatment of coronary artery diseases.
However, the role and effectiveness of PCI with a bare metal stent (BMS) have not
yet been established. METHODS: Among the 2197 patients (2653 lesions) treated
with PCI from 2003 to 2012 at three institutions in Fukuoka, 859 patients (1032
lesions) without acute coronary syndrome and in whom we were able to perform
follow-up coronary angiography after stent placement and collect detailed data
were selected for this study. Among the patients treated by BMS, the cut-off
lesion reference for the development of in-stent restenosis (ISR) was calculated
by comparing patients with and without ISR. In all patients with a lesion
reference above/below the cut-off point of BMS-ISR, medium-term clinical and
angiographic outcomes were compared between the BMS and DES groups. RESULTS: In
patients treated with a BMS, the lesion reference [odds ratio 0.68, 95%
confidence interval (CI) 0.43-0.97, p=0.03] was strongly correlated with ISR, and
the area under the receiver operating characteristic curve was 0.704, with
moderate accuracy. Calculation of the cut-off lesion reference for BMS-ISR, using
a relative cumulative frequency distribution and a sensitivity/specificity curve,
showed that the cut-off lesion reference for BMS-ISR was 3.08mm, and the
sensitivity/specificity was 60.4%. For the DES and BMS groups in cases with a
lesion reference over 3.08mm, BMS placement did not correlate with ISR (odds
ratio 0.98, 95% CI 0.85-1.12), and there was also no correlation between BMS and
major adverse cardiac events. CONCLUSION: In patients with a lesion
reference?3.08mm, medium-term clinical and angiographic outcomes were equivalent
between the use of a DES and BMS. Thus, BMS placement is well worth considering,
especially in patients with a lesion reference?3.08mm, in whom double
antiplatelet therapy needs to be stopped at an early stage.
PMID- 27492660
TI - Efficient and stereocontrolled synthesis of chondroitin mono- and disaccharide
linked to variously sulfated biotinylated trisaccharides of the linkage region of
proteoglycans.
AB - Efficient and stereocontrolled preparation of a library of variously sulfated
biotinylated tetra- and pentasaccharides possessing the backbone of the partial
linkage region plus the first chondroitin sulfate mono- or disaccharide unit (d
GlcA)n-beta-d-(1,3)-GalNAc-beta-d-(1,4)-GlcA-beta-d-(1,3)-Gal-beta-d-(1,3)-Gal (n
= 0 or 1) is reported herein for the first time. The synthesis of these compounds
was achieved using common key intermediates and a disaccharide building block
obtained by semisynthesis. Stereoselective glycosylation, selective
protection/deprotection steps, efficient reduction of the N-trichloroacetyl group
into the corresponding N-acetyl group, efficient sulfation strategy, deprotection
and biotinylation afforded target oligomers in good yield with high purity.
PMID- 27492659
TI - Severe prosthesis-patient mismatch after aortic valve replacement for aortic
stenosis: Analysis of risk factors for early and long-term mortality.
AB - BACKGROUND: Severe prosthesis-patient mismatch (PPM) is considered to further
decrease survival compared to moderate PPM. This study aimed to assess the impact
of severe PPM on survival after aortic valve replacement (AVR). METHODS: We
retrospectively studied 2404 consecutive patients with PPM who underwent first
time AVR for pure stenosis between January 2003 and December 2014. Mismatch was
moderate for indexed effective valve orifice >0.65 to <0.85cm2/m2 and severe for
indexed effective valve orifice <=0.65cm2/m2. Moderate mismatch occurred in 2165
patients (89%), and severe in 239 (11%) patients. Logistic multiple regression
with bootstrapping and propensity score analyses were performed using 29 clinical
and demographic data to assess the risk-adjusted impact of severe mismatch on
mortality. The Cox proportional hazards model was constructed to process the long
term outcome. RESULTS: Early mortality was 2.3% (51/2165) in moderate mismatch
group and 3.7% (9/239) in severe mismatch group (p=0.2). Mortality at 5 and 10
years, was 218/1470 (14.8%) and 252/585 (43.1%) for moderate mismatch and 43/198
(21.7%) and 61/105 (58.1%) for severe mismatch (p=0.02 and p=0.006).
Multivariable predictors of late mortality were as follows: age >=70 years, left
ventricular ejection fraction <=40%, indexed left ventricular mass >220g/m2 and
concomitant coronary artery revascularization. After propensity score matching,
conditional logistic regression analysis demonstrated no relationship between
severe mismatch and increased mortality at 5 postoperative years (HR, 0.9; 95%
CI, 0.7-1.6; p=0.06), whereas it was significant at 10 postoperative years (HR,
1.9; 95% CI, 1.2-2.5; p=0.03). During the follow-up, severe mismatch was
associated with more frequent hospital readmissions for cardiac events (0.12 vs.
0.08 events/patient/year, p=0.007). CONCLUSIONS: Patients with severe mismatch
had lower long-term survival and higher incidence of hospital readmissions for
cardiac events. However, the effect of severe mismatch on outcome appeared mainly
related to the preoperative risk profile of each patient.
PMID- 27492661
TI - Calls to suspend European sales of erlotinib for lung cancer.
PMID- 27492662
TI - Open-Shell-Character-Based Molecular Design Principles: Applications to Nonlinear
Optics and Singlet Fission.
AB - Open-shell character, e. g., diradical character, is a quantum chemically well
defined quantity in ground-state molecular systems, which is not an observable
but can quantify the degree of effective bond weakness in the chemical sense or
electron correlation strength in the physical sense. Because this quantity also
correlates to specific excited states, physicochemical properties concerned with
those states are expected to strongly correlate to the open-shell character. This
feature enables us to open a new path to revealing the mechanism of these
properties as well as to realizing new design principles for efficient functional
molecular systems. This account explains the open-shell-character-based molecular
design principles and introduces their applications to the rational design of
highly efficient nonlinear optical and singlet fission molecular systems.
PMID- 27492663
TI - Temporal evolution of urate crystal deposition over articular cartilage after
successful urate-lowering therapy in patients with gout: An ultrasonographic
perspective.
AB - OBJECTIVE: To detect evolution of ultrasonographic signs of deposition of
monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after
initiation of urate-lowering therapy (ULT). METHODS: Adult gout patients were
examined by serial ultrasonography after initiation of ULT with target serum uric
acid (SUA) < 6 mg/dL. RESULTS: Thirty-eight male patients with gout with mean age
of 50 +/- 11 years, median disease duration of 48 months and baseline mean SUA
level of 8.8 +/- 1.5 mg/dL were recruited. Ultrasonographic evidence of MSUC
deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and
27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots
(HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively.
SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness
reduced significantly throughout the follow-up period. Overall, 86.25% DCS and
100% HES disappeared with median time of 6 months and 5.7 months, respectively.
SUA normalization was the only significant predictor of DCS disappearance.
CONCLUSIONS: Serial ultrasonographic determination of DCS, tophi, or HES during
hypouricemic therapy is a noninvasive, effective method to detect the lowering of
burden of urate load in gouty joints.
PMID- 27492664
TI - A Novel Strategy for Preparation of Si-HA Coatings on C/C Composites by Chemical
Liquid Vaporization Deposition/Hydrothermal Treatments.
AB - A novel strategy for the preparation of Si-doped hydroxyapatite (Si-HA) coatings
on H2O2-treated carbon/carbon composites (C/C) was developed. HA coating was
prepared on C/C through chemical liquid vaporization deposition
(CLVD)/hydrothermal treatment. HA coating was immersed in an H2SiO3 solution at
an autoclave at 413 K for transformation into Si-HA coating. The effects of
H2SiO3 mass contents on the phase, morphology, and composition of the Si-HA
coatings were studied through SEM, EDS,XRD, and FTIR. Their bonding performance
to C/C was measured through a scratch test. Under the optimal content condition,
the in vitro skull osteoblast response behaviors of the Si-HA coating were
evaluated. Results showed that SiO3(2-) could enter into the HA lattice and
occupy the PO4(3-) sites. Doped SiO3(2-) significantly improved the bonding
performance of the HA coating to C/C in comparison with the untreated HA. The
adhesive strength of the coatings initially increased and then decreased with
increasing H2SiO3 content. Meanwhile, the cohesive strength of the Si-HA coatings
was almost nearly identical. The Si-HA coating achieved at a content of 90%
H2SiO3 exhibited the best bonding performance, and its osteoblast compatibility
in vitro was superior to that of the untreated HA coating on C/C through
CLVD/hydrothermal treatment.
PMID- 27492665
TI - Editorial Comment.
PMID- 27492666
TI - Author Reply.
PMID- 27492667
TI - Author Reply.
PMID- 27492668
TI - Editorial Comment.
PMID- 27492669
TI - The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2016 Update
on Research.
AB - The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD) is
the largest congenital and pediatric cardiac surgical clinical data registry in
the world. With more than 400,000 total operations from nearly all centers
performing pediatric and congenital heart operations in North America, the STS
CHSD is an unparalleled platform for clinical investigation, outcomes research,
and quality improvement activities in this subspecialty. In 2015, several major
original publications reported analyses of data in the CHSD pertaining to
specific diagnostic and procedural groups, age-defined cohorts, or the entire
population of patients in the database. Additional publications reported the most
recent development, evaluation, and application of metrics for quality
measurement and reporting of pediatric and congenital heart operation outcomes.
This use of the STS CHSD for outcomes research and for quality measurement
continues to expand as database participation and the available wealth of data in
it continue to grow. This article reviews outcomes research and quality
improvement articles published in 2015 based on STS CHSD data.
PMID- 27492670
TI - The University of Minnesota Donor Lung Quality Index: A Consensus-Based Scoring
Application Improves Donor Lung Use.
AB - BACKGROUND: A simplified and consensus-based donor scoring process could improve
donor lung use. METHODS: To develop the University of Minnesota Donor Lung
Quality Index (UMN-DLQI), we used expert opinion to create an online survey that
ranked 17 lung donor and recipient factors and graded their importance on a scale
of 0 to 10. To arrive at consensus-based weights for each of the 17 factors, we
used magnitude estimation (ME) methods. We performed receiver operating
characteristic (ROC) analyses to evaluate predictive value. An application (app)
was developed to simplify the scoring process. A second review process was
instituted for every donor offer with an UMN-DLQI score greater than 40 as of
September 2014 (post-donor score era). RESULTS: Worldwide, 11 transplantation
centers (including ours) completed our survey. Results showed strong consensus
among transplantation physicians across disparate practices. UMN-DLQI scores
greater than 40 provided a sensitivity of 89%, a specificity of 55%, and a
positive predictive value of 52% for donor offer acceptance. Number of
transplants (63 versus 48) and donor lung use (15.1% versus 8.9%; p = 0.02) were
significantly better in the post-donor score era without a penalty in
transplantation outcomes. There was a trend toward a lower incidence of any
primary graft dysfunction within 72 hours (40% versus 75%; p = 0.06) with a UMN
DLQI greater than 40 but no difference in 30-day or 1-year survival. CONCLUSIONS:
The UMN-DLQI scoring app is a simple tool for describing the attributes of a
donor lung offer. More attention to scores greater than 40 safely improved donor
lung use at a single institution.
PMID- 27492672
TI - What about caregiving in spinal cord injury?
PMID- 27492673
TI - Anxiety prevalence following spinal cord injury: a meta-analysis.
PMID- 27492671
TI - Modeling the Myxomatous Mitral Valve With Three-Dimensional Echocardiography.
AB - BACKGROUND: Degenerative mitral valve disease is associated with variable and
complex defects in valve morphology. Three-dimensional echocardiography (3DE) has
shown promise in aiding preoperative planning for patients with this disease but
to date has not been as transformative as initially predicted. The clinical
usefulness of 3DE has been limited by the laborious methods currently required to
extract quantitative data from the images. METHODS: To maximize the utility of
3DE for preoperative valve evaluation, this work describes an automated 3DE image
analysis method for generating models of the mitral valve that are well suited
for both qualitative and quantitative assessment. The method is unique in that it
captures detailed alterations in mitral leaflet and annular morphology and
produces image-derived models with locally varying leaflet thickness. The method
is evaluated on midsystolic transesophageal 3DE images acquired from 22 subjects
with myxomatous degeneration and from 22 subjects with normal mitral valve
morphology. RESULTS: Relative to manual image analysis, the automated method
accurately represents both normal and complex leaflet geometries with a mean
boundary displacement error on the order of one image voxel. A detailed
quantitative analysis of the valves is presented and reveals statistically
significant differences between normal and myxomatous valves with respect to
numerous aspects of annular and leaflet geometry. CONCLUSIONS: This work
demonstrates a successful methodology for the relatively rapid quantitative
description of the complex mitral valve distortions associated with myxomatous
degeneration. The methodology has the potential to significantly improve surgical
planning for patients with complex mitral valve disease.
PMID- 27492674
TI - Does an Online CBT Program for Anxiety Impact Upon Sleep Problems in Anxious
Youth?
AB - This study aimed to assess whether the transdiagnostic therapy elements of an
online cognitive behaviour therapy anxiety program also impact on sleep-related
problems (SRPs) in anxious youth. Participants were drawn from two previously
published studies evaluating online cognitive behaviour therapy for child anxiety
(BRAVE-ONLINE). The study included 63 children 7-12 years of age (M = 9.49, SD =
1.37) and 71 adolescents 12-18 years of age (M = 13.90, SD = 1.68). SRPs,
severity of anxiety diagnosis, anxiety symptoms, number of diagnoses, depressive
symptoms, and global functioning were assessed at pre-, post-, and 6-month follow
up assessment points. SRPs were positively related to anxiety symptoms and
severity for children and were positively related to depression for adolescents.
SRPs did not differ between male and female participants, between children and
adolescents, or between those who had generalised anxiety disorder in their
profile and those who did not. Finally, children but not adolescents
participating in the online program demonstrated a significantly greater
reduction in SRPs from pre- to posttreatment compared to the waitlist group, and
these gains were maintained at 6-month follow-up. Treatment focusing on child
anxiety alone may reduce SRPs in children but not adolescents. Although further
research is clearly needed, clinicians should ensure that they assess for SRPs in
their teenage clients and directly target SRPs in treatment where required.
PMID- 27492675
TI - Hallucinatory experience as aberrant event memory formation: Implications for the
pathophysiology of schizophrenia.
AB - If hallucinations are not fundamentally different from normal wakeful
experiences, then the neural basis of hallucinations has to be essentially that
of consciousness in general. The additional insight that consciousness reflects
the formation (as opposed to consolidation) of event (episodic) memories links
the pathophysiology of hallucinations to the hippocampus. Perceptions and
misperceptions, insofar as they are consciously experienced, constitute
contextualized and unitary phenomena (which are embedded as discrete events in
the stream of consciousness); they are experiential manifestations of activity
patters that recurrently emerge in the CA3 network of the hippocampus (and that
are secondarily consolidated into retrievable and declarable memories). The
hippocampus, forming allocentric representations of objects in their world
context (event memories), is a point of convergence of neocortical sensory
processing streams. Moreover, being extensively modulated by the organism's
physiological state, the hippocampus embeds such representations in an emotional
context and, through its output to the medial prefrontal cortex, guides decision
making and goal-selection processes. Although sensory and associative processing
in the neocortex makes an important contribution to the formation of
behaviourally adaptive representations in the hippocampus, it is becoming clearer
that pattern formation in the hippocampus is in itself the neural correlate of
consciousness and that disruptions in relational memory processing in the
hippocampus can give rise to hallucinations. Neurobiological and neuroimaging
findings in schizophrenia research can be integrated within the proposed
conceptual framework.
PMID- 27492676
TI - Substance Abuse Treatment Patients in Housing Programs Respond to Contingency
Management Interventions.
AB - Use of homeless and transitional housing (e.g., recovery homes) programs can be
associated with success in substance abuse treatment, perhaps because many of
these programs encourage or mandate sobriety. In this study, we examined whether
contingency management (CM) protocols that use tangible incentives for submission
of drug-free specimens or other specific behaviors are effective for treatment
seeking substance abusers whose behavior may also be shaped by housing programs.
Of 355 participants in randomized trials of CM, 56 (16%) reported using
transitional housing during the 12-week treatment period. Main and interaction
effects of housing status and treatment condition were evaluated for the primary
substance abuse treatment outcomes: a) longest duration of abstinence from
alcohol, cocaine, and opioids, b) percentage of samples submitted that were
negative for these substances, and c) treatment retention. After controlling for
demographic and clinical characteristics, those who accessed housing programs
submitted a higher percentage of negative samples (75%) compared to those who did
not access housing programs (67%). Housing status groups did not differ in terms
of longest duration of abstinence (accessed housing: M=3.1 weeks, SE=0.6; did not
access housing: M=3.9 weeks, SE=0.3) or retention in substance abuse treatment
(accessed housing: M=6.4 weeks, SE=0.6; did not access housing: M=6.6 weeks,
SE=0.3). Regardless of housing status, CM was associated with longer durations of
abstinence and treatment retention. No interactive effects of housing and
treatment condition were observed (p>.05). Results suggest that those who
accessed housing programs during substance abuse treatment benefit from CM to a
comparable degree as their peers who did not use such programs. These effects
suggest that CM remains appropriate for those accessing housing in community
based programs.
PMID- 27492677
TI - Diabetes drugs in England cost nearly L1bn last year.
PMID- 27492679
TI - Celiac Disease Presenting as Profound Diarrhea and Weight Loss - A Celiac Crisis.
AB - BACKGROUND Celiac disease is a hypersensitivity enteropathy that can have various
presentations in adults. Rarely, patients can present with severe lab
abnormalities, dehydration and weight loss caused by celiac disease - a celiac
crisis. CASE REPORT A 46-year-old male with a past medical history significant
for diabetes mellitus, type 2 (DM2) and recently treated Bell's Palsy presented
to the emergency room complaining of weakness, diarrhea and lightheadedness. On
presentation, the patient had a systolic blood pressure (SBP) of 60 mm Hg and a
lactic acidosis with pH of 7.28. Infectious etiologies of diarrhea were ruled
out. The patient had an EGD which showed erythema of the duodenal bulb. Serum
anti-gliadin and anti-TTG IgA were both elevated suggesting Celiac disease.
Biopsies showed histopathology consistent with celiac disease. The patient's
diarrhea resolved after initiation of a gluten free diet. He gained 25 kilograms
after discharge and did not require further hospitalizations for diarrhea.
CONCLUSIONS Celiac crisis is a very rare presentation of celiac disease in adults
but nonetheless should be considered in patients with marked metabolic
derangements in the setting of osmotic diarrhea. Treatment consists of a gluten
free diet and may require management with steroids and total parenteral nutrition
(TPN).
PMID- 27492678
TI - Economic growth, urbanization, globalization, and the risks of emerging
infectious diseases in China: A review.
AB - Three interrelated world trends may be exacerbating emerging zoonotic risks:
income growth, urbanization, and globalization. Income growth is associated with
rising animal protein consumption in developing countries, which increases the
conversion of wild lands to livestock production, and hence the probability of
zoonotic emergence. Urbanization implies the greater concentration and
connectedness of people, which increases the speed at which new infections are
spread. Globalization-the closer integration of the world economy-has facilitated
pathogen spread among countries through the growth of trade and travel. High-risk
areas for the emergence and spread of infectious disease are where these three
trends intersect with predisposing socioecological conditions including the
presence of wild disease reservoirs, agricultural practices that increase contact
between wildlife and livestock, and cultural practices that increase contact
between humans, wildlife, and livestock. Such an intersection occurs in China,
which has been a "cradle" of zoonoses from the Black Death to avian influenza and
SARS. Disease management in China is thus critical to the mitigation of global
zoonotic risks.
PMID- 27492680
TI - Size dependent microbial oxidation and reduction of magnetite nano- and micro
particles.
AB - The ability for magnetite to act as a recyclable electron donor and acceptor for
Fe-metabolizing bacteria has recently been shown. However, it remains poorly
understood whether microbe-mineral interfacial electron transfer processes are
limited by the redox capacity of the magnetite surface or that of whole
particles. Here we examine this issue for the phototrophic Fe(II)-oxidizing
bacteria Rhodopseudomonas palustris TIE-1 and the Fe(III)-reducing bacteria
Geobacter sulfurreducens, comparing magnetite nanoparticles (d ~ 12 nm) against
microparticles (d ~ 100-200 nm). By integrating surface-sensitive and bulk
sensitive measurement techniques we observed a particle surface that was enriched
in Fe(II) with respect to a more oxidized core. This enables microbial Fe(II)
oxidation to occur relatively easily at the surface of the mineral suggesting
that the electron transfer is dependent upon particle size. However, microbial
Fe(III) reduction proceeds via conduction of electrons into the particle
interior, i.e. it can be considered as more of a bulk electron transfer process
that is independent of particle size. The finding has potential implications on
the ability of magnetite to be used for long range electron transport in soils
and sediments.
PMID- 27492681
TI - A Novel Fluorimetric Bulk Optode Membrane Based on NOS Tridentate Schiff Base for
Selective Optical Sensing of Al3+ Ions.
AB - A novel fluorimetric optode has been developed for the highly selective and
sensitive for the determination of ultra trace amounts of Al3+ ions. The proposed
fluorescent optode is based on the incorporation of a simple and effective
fluorescent sensor tridentate NOS Schiff base N-(2-hydroxynaphthylidene)-2
aminothiophenol (H2L) in a plasticized PVC containing KTpClPB as a lipophilic
anionic additive. H2L was synthesized by a facile one-step Schiff base reaction.
The plasticized PVC-membrane displays a calibration response for Al3+ ions over a
wide concentration range from 1.0 * 10-9 to 4.4 * 10-3 mol/L. The fluorescence
signal of the optode membrane can be easily recovered by immersion in 0.01 M
EDTA. In addition to high stability and reproducibility, the sensor shows a
unique selectivity towards Al3+ ion with respect to common co-existing cations,
particularly Ga3+and In3+. The proposed optode was applied successfully for
determination of Al3+ in some real samples, including bottled drinking waters,
bottled mineral waters and soft drinks.
PMID- 27492682
TI - RhoGTPases at the synapse: An embarrassment of choice.
AB - Activity-dependent modifications in the strength of excitatory synapses are
considered to be major cellular mechanisms that contribute to the plasticity of
neuronal networks underlying learning and memory. Key mechanisms for the
regulation of synaptic efficacy involve the dynamic changes in size and number of
dendritic spines, as well as the synaptic incorporation and removal of AMPA-type
glutamate receptors (AMPAr). As key regulators of the actin cytoskeleton, the Rho
subfamily of GTP-binding proteins play a critical role in synaptic development
and plasticity. They shuttle between the active GTP-bound form and the inactive
GDP-bound form under the regulation of dedicated guanine nucleotide exchange
factors (GEFs) and GTPase-activating proteins (GAPs). More than 80 human GEFs and
70 GAPs have been identified, most of which are expressed in the brain with a
specific spatial and temporal expression pattern. However, the function of most
GEFs and GAPs in the brain has not been elucidated. In this review, we highlight
the novel neuronal function of the synaptic RhoGAP ARHGAP12 and the ID-associated
RhoGEF TRIO and further propose 3 possible approaches of neurons utilizing Rho
GTPase regulatory proteins to accurately modulate synaptic function.
PMID- 27492683
TI - Antimicrobial susceptibility of lactic acid bacteria isolated from human and food
producing animal feces in Khon Kaen Province, Thailand.
AB - The aim of this study was to investigate the susceptibility of 93 Lactobacillus
strains to seven antimicrobial agents, i.e., penicillin G, amoxicillin-clavulanic
acid, vancomycin, tetracycline, streptomycin, ciprofloxacin, and sulfamethoxazole
trimethoprim, by disk diffusion test. The Lactobacillus strains were isolated
from fecal samples taken from 90 healthy, food-producing animals (fattening pigs,
free-grazing ducks, and beef cattle) and 30 healthy human subjects (1- to 6-year
olds) in Khon Kaen. The minimum inhibitory concentration (MIC) values of
tetracycline and ciprofloxacin against all strains were determined using the E
test. All 93 Lactobacillus isolates were identified at the species level using
16S rRNA gene sequencing. The most common species of Lactobacillus isolated from
fattening pigs, free-grazing ducks, beef cattle, and humans were L. reuteri (30
%), L. salivarius (46.7 %), L. acetotolerans (20 %), and L. gasseri (33.3 %),
respectively. A total of 83 Lactobacillus strains were resistant to the examined
antibiotics. Some strains were resistant to two to six types of antibiotics. More
than 50 % of Lactobacillus species were intrinsically resistant to vancomycin,
streptomycin, ciprofloxacin, and sulfamethoxazole-trimethoprim. The prevalence of
acquired resistance to tetracycline was observed for Lactobacillus isolates from
fattening pigs, humans, free-grazing ducks, and beef cattle at 92.3, 85.7, 77.8,
and 68.4 %, respectively. These results demonstrate the impact of antibiotic use
in human and veterinary medicine on antibiotic treatment efficacy and may support
the spread of transferable antibiotic resistant genes to other bacteria via the
food chain.
PMID- 27492684
TI - Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces
mucosal inflammation in murine colitis.
AB - Targeted disruption of leukocyte trafficking to the gut represents a promising
approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the
shared receptor for MIP1alpha and beta and RANTES, is expressed by multiple
leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte
trafficking in models of colitis, and evaluate the therapeutic potential of
maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic
HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to
wild-type and CCR5(-/-) mice or adoptive transfer of splenic naive CD4(+) T-cells
from wild type or CCR5(-/-) mice into RAG-1(-/-). CCR5 gene ablation reduced the
mucosal recruitment and activation of CCR5-bearing CD4(+) and CD11b(+)
leukocytes, resulting in profound attenuation of signs and symptoms of
inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis
and in the transfer model, maraviroc attenuated development of intestinal
inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes.
In summary, CCR5 regulates recruitment of blood leukocytes into the colon
indicating that targeting CCR5 may offer therapeutic options in IBDs.
PMID- 27492685
TI - Neighborhood Stigma and Sleep: Findings from a Pilot Study of Low-Income Housing
Residents in New York City.
AB - The primary objective of this study was to investigate the relationship between
neighborhood stigma and sleep in a sample of low-income housing residents in New
York City. Data were derived from the NYC Low-Income Housing, Neighborhoods, and
Health Study (N = 120). Adults living in low-income housing completed a survey
consisting of measures of neighborhood stigma, sleep quality, and sleep duration.
Neighborhood stigma and sleep were self-reported. Associations between
neighborhood stigma and sleep health were analyzed using generalized linear
models with cluster variance estimation. Multivariable models adjusted for age,
gender, race/ethnicity, income, education, employment status, obesity, the census
block percentage of non-Hispanic black residents, and the census block percentage
median household income. Results indicate that a reported negative media
perception of the neighborhood was negatively associated with sleep quality and
duration (p < 0.01). However, additional research is needed to explore
neighborhood stigma as it relates to sleep.
PMID- 27492686
TI - Satisfying Results of Primary Hip Arthroplasty in Patients With Hip Dysplasia at
a Mean Followup of 20 Years.
AB - BACKGROUND: Developmental dysplasia of the hip (DDH) is a common cause of
secondary osteoarthritis (OA) in younger patients, and when end-stage OA
develops, a THA can provide a solution. Different options have been developed to
reconstruct these defects, one of which is impaction bone grafting combined with
a cemented cup. To determine the true value of a specific technique, it is
important to evaluate patients at a long-term followup. As there are no long-term
studies, to our knowledge, on THA in patients with DDH using impaction bone
grafting with a cemented cup, we present the results of this technique at a mean
of 15 years in patients with previous DDH. QUESTIONS/PURPOSES: We wished to
determine (1) the long-term probability of cup revision at a minimum followup of
15 years for cemented acetabular impaction bone grafting in patients with DDH;
(2) the radiographic appearance of the bone graft and radiographic signs of
implant loosening; and (3) the complications and pre- and postoperative Harris
hip scores with cemented THA combined with impaction bone grafting in patients
with previous DDH. METHODS: Between January 1984 and December 1995 we performed
28 acetabular impaction bone grafting procedures for secondary OA believed to be
caused by DDH in 22 patients; four patients died before 15 years, leaving 24 hips
in 18 patients for retrospective analysis at a minimum of 15 years (mean, 20
years; range, 16-29 years). The diagnosis of DDH was made according to
preoperative radiographs and intraoperative findings. All grades of dysplasia
were included; five patients had Crowe Group I, eight had Group II, nine had
Group III, and two had Group IV DDH. No patients were lost to followup. In all
cases the acetabular defects were combined cavitary and segmental. Owing to the
high number of deaths, we performed a competing-risk analysis to determine the
probability of cup revision surgery. RESULTS: The competing-risk analysis showed
cumulative incidences at 15 and 20 years, with endpoint revision for any reason
of 7% (95% CI, 0%-17%), whereas this was 4% (95% CI, 0%-11%) with endpoint
revision of the cup for aseptic loosening. Three revision surgeries were
performed. Two cup revisions were performed for aseptic loosening at 12 and 26
years. Another cup revision was performed owing to sciatic nerve problems at 2
years. A stable radiographic appearance of the graft was seen in 19 of the 25
unrevised hips. Four hips showed acetabular radiolucent lines and two showed
acetabular osteolysis. None of the unrevised cups showed migration or
radiographic failure. Postoperative complications included a pulmonary embolus
and a superficial wound infection. The Harris hip score improved from 37 (range,
9-72) preoperatively to 83 (range, 42-99) at latest followup. CONCLUSIONS:
Cemented primary THA with the use of impaction bone grafting shows satisfying
long-term results in patients with previous DDH. For future research it is
important to evaluate this technique in a larger cohort with a long-term
followup. Other techniques also should be evaluated at long-term followup to be
able to compare different techniques in this important and specific patient
group. LEVEL OF EVIDENCE: Level IV, therapeutic study.
PMID- 27492687
TI - Novel Augmentation Technique for Patellar Tendon Repair Improves Strength and
Decreases Gap Formation: A Cadaveric Study.
AB - BACKGROUND: Patellar tendon ruptures commonly are repaired using transosseous
patellar drill tunnels with modified-Krackow sutures in the patellar tendon. This
simple suture technique has been associated with failure rates and poor clinical
outcomes in a modest proportion of patients. Failure of this repair technique can
result from gap formation during loading or a single catastrophic event. Several
augmentation techniques have been described to improve the integrity of the
repair, but standardized biomechanical evaluation of repair strength among
different techniques is lacking. QUESTIONS/PURPOSES: The purpose of this study
was to describe a novel figure-of-eight suture technique to augment traditional
fixation and evaluate its biomechanical performance. We hypothesized that the
augmentation technique would (1) reduce gap formation during cyclic loading and
(2) increase the maximum load to failure. METHODS: Ten pairs (two male, eight
female) of fresh-frozen cadaveric knees free of overt disorders or patellar
tendon damage were used (average donor age, 76 years; range, 65-87 years). For
each pair, one specimen underwent the standard transosseous tunnel suture repair
with a modified-Krackow suture technique and the second underwent the standard
repair with our experimental augmentation method. Nine pairs were suitable for
testing. Each specimen underwent cyclic loading while continuously measuring gap
formation across the repair. At the completion of cyclic loading, load to failure
testing was performed. RESULTS: A difference in gap formation and mean load to
failure was seen in favor of the augmentation technique. At 250 cycles, a 68%
increase in gap formation was seen for the control group (control: 5.96 +/- 0.86
mm [95% CI, 5.30-6.62 mm]; augmentation: 3.55 +/- 0.56 mm [95% CI, 3.12-3.98 mm];
p = 0.02). The mean load to failure was 13% greater in the augmentation group
(control: 899.57 +/- 96.94 N [95% CI, 825.06-974.09 N]; augmentation: 1030.70 +/-
122.41 N [95% CI, 936.61-1124.79 N]; p = 0.01). CONCLUSIONS: This biomechanical
study showed improved performance of a novel augmentation technique compared with
the standard repair, in terms of reduced gap formation during cyclic loading and
increased maximum load to failure. CLINICAL RELEVANCE: Decreased gap formation
and higher load to failure may improve healing potential and minimize failure
risk. This study shows a potential biomechanical advantage of the augmentation
technique, providing support for future clinical investigations comparing this
technique with other repair methods that are in common use such as transosseous
suture repair.
PMID- 27492689
TI - A response to: "Evaluation of pain".
PMID- 27492688
TI - When Can I Drive After Orthopaedic Surgery? A Systematic Review.
AB - BACKGROUND: Patients often ask their doctors when they can safely return to
driving after orthopaedic injuries and procedures, but the data regarding this
topic are diverse and sometimes conflicting. Some studies provide observer
reported outcome measures, such as brake response time or simulators, to estimate
when patients can safely resume driving after surgery, and patient survey data
describing when patients report a return to driving, but they do not all agree.
We performed a systematic review and quality appraisal for available data
regarding when patients are safe to resume driving after common orthopaedic
surgeries and injuries affecting the ability to drive. QUESTIONS/PURPOSES: Based
on the available evidence, we sought to determine when patients can safely return
to driving after (1) lower extremity orthopaedic surgery and injuries; (2) upper
extremity orthopaedic surgery and injuries; and (3) spine surgery. METHODS: A
search was performed using PubMed and EMBASE(r), with a list of 20 common
orthopaedic procedures and the words "driving" and "brake". Selection criteria
included any article that evaluated driver safety or time to driving after major
orthopaedic surgery or immobilization using observer-reported outcome measures or
survey data. A total of 446 articles were identified from the initial search, 48
of which met inclusion criteria; abstract-only publications and non-English
language articles were not included. The evidence base includes data for driving
safety on foot, ankle, spine, and leg injuries, knee and shoulder arthroscopy,
hip and knee arthroplasty, carpal tunnel surgery, and extremity immobilization.
Thirty-four of the articles used observer-reported outcome measures such as total
brake time, brake response time, driving simulator, and standardized driving
track results, whereas the remaining 14 used survey data. RESULTS: Observer
reported outcome measures of total brake time, brake response time, and brake
force postoperatively suggested patients reached presurgical norms 4 weeks after
right-sided procedures such as TKA, THA, and ACL reconstruction and approximately
1 week after left-sided TKA and THA. The collected survey data suggest patients
resumed driving 1 month after right-sided and left-sided TKAs. Patients who had
THA reported returning to driving between 6 days and 3 months postoperatively.
Observer-reported outcome measures showed that patients' driving abilities often
are impaired when wearing an immobilizing cast above or below the elbow or a
shoulder sling on their dominant arm. Patients reported a return to driving on
average 2 months after rotator cuff repair procedures and approximately 1-3
months postoperatively for total shoulder arthroplasties. Most patients with
spine surgery had normal brake response times at the time of hospital discharge.
Patients reported driving 6 weeks after total disc arthroplasty and anterior
cervical discectomy and fusion procedures. CONCLUSIONS: The available evidence
provides a best-case scenario for when patients can return to driving. It is
important for observer-reported outcome measures to have normalized before a
patient can consider driving, but other factors such as strength, ROM, and use of
opioid analgesics need to be considered. This review can provide a guideline for
when physicians can begin to consider evaluating these other factors and
discussing a return to driving with patients. Survey data suggest that patients
are returning to driving before observer-reported outcome measures have
normalized, indicating that physicians should tell patients to wait longer before
driving. Further research is needed to correlate observer-reported outcome
measures with adverse events, such as motor vehicle accidents, and clinical tests
that can be performed in the office. LEVEL OF EVIDENCE: Level III, therapeutic
study.
PMID- 27492690
TI - Reimbursment of the serum CTX assay in France: the clinical biology nomenclature
is incoherent.
PMID- 27492691
TI - Interest of fecal calprotectine dosage in inflammatory bowel diseases, state of
the art and perspectives.
AB - Inflammatory bowel diseases are chronic diseases that result from an inflammation
of the intestinal wall. They are suspected in any patient presenting with
intestinal symptoms. Until recently, diagnosis was mainly based both on clinical
and endoscopic arguments. The use of an easy, fast, reliable, non-invasive and
inexpensive test must not only assist in the diagnosis but also contribute to
their evolutionary and therapeutic monitoring. To date, fecal calprotectin is the
most documented in this perspective. This marker allows to discriminate between
functional and organic bowel processes with good sensitivity and good
specificity. The determination of the fecal calprotectin level in stools
contributes to the evaluation of the degree of disease activity and monitoring of
therapeutic response.
PMID- 27492692
TI - Circulating endothelial cells: a new biomarker of endothelial dysfunction in
hematological diseases.
AB - The endothelium and its integrity are in the center of numerous cardiovascular,
pulmonary and tumoral diseases. Several studies identified different circulating
cellular sub-populations, which allow a noninvasive exploration of endothelial
dysfunction. Furthermore, angiogenesis plays a major role in the biology of
benign and malignant hematologic diseases. Among these biomarkers, circulating
endothelial cells could be considered as a marker of endothelial injury and/or
endothelial activation as well as vascular remodeling, whereas circulating
endothelial progenitor cells would be only involved in the vascular regeneration.
In the future, the quantification of circulating endothelial cells in many
diseases could be a noninvasive biomarker used in diagnosis, prognostic and
therapeutic follow-up of lung vasculopathy and/or residual disease of
hematological malignancies.
PMID- 27492693
TI - Diagnosis of congenital fibrinogen disorders.
AB - Congenital fibrinogen disorders comprise quantitative disorders defined by a
complete absence (afibrinogenemia) or by a decreased level (hypofibrinogenemia)
of circulating fibrinogen and qualitative disorders characterized by a
discrepancy between the activity and the antigenic levels of fibrinogen
(dysfibrinogenemia and hypodysfibrinogenemia). The biological diagnosis is based
on a standard haemostasis assessment. All the coagulation tests that depend on
the formation of fibrin as the end point are affected; although in
dysfibrinogenemia the specificity and sensitivity of routine test depend on
reagent and techniques. A genetic exploration permits to confirm the diagnosis
and may enhance the prediction of the patient's phenotype. Homozygous or
composite heterozygous null mutations are most often responsible for
afibrinogenemia while hypofibrinogenemic patients are mainly heterozygous carrier
of an afibrinogenemic allele. Heterozygous missense mutations are prevalent in
dysfibrinogenemia, with two hot spot localized in exon 2 of the FGA and in the
exon 8 of the FGG. The correlation between phenotype and genotype has been
identified in some fibrinogen variants, including six mutations clustered in
exons 8 and 9 of the FGG leading to hypofibrinogenemia with hepatic inclusions of
abnormal fibrinogen aggregates as well as a few mutations associated with an
increase risk of thrombotic events. A familial screening and additional
functional assays should be carried out when possible.
PMID- 27492694
TI - How to interpret cardiac biomarkers in renal failure and elderly?
AB - New highly sensitive (hs) assays have challenged the interpretation of cardiac
troponins (cTn) as markers of injury while natriuretic peptides remain the
markers of choice for myocardial dysfunction. However, variability extracardiac
factors such as age, gender and renal function may alter circulating levels. In
chronic kidney disease (CKD), the increase in circulating levels of these
biomarkers in the absence of cardiac disease underlines the problem of
discriminative value for diagnosis as well as the need to redefine the
thresholds. In addition, these biomarkers are of potential interest to stratify
cardiovascular risk, the leading cause of death in CKD. The aim of this work is
to clarify the effect of age and renal function on circulating levels of high
sensitivity troponins and natriuretic peptides.
PMID- 27492695
TI - Lactobacillus crispatus as biomarker of the healthy vaginal tract.
AB - Decades of research have shown that the lactobacilli inhabiting the human vagina
are the first line of defense in the female urogenital and reproductive tracts.
In healthy cervicovaginal microbiota, Lactobacillus crispatus is prevalent and
beneficial with production of copious amounts of lactic acid potent broad
spectrum bactericide virucide and immunomodulator. Future and preventic
approaches may need to include probiotics, prebiotics also have the potential to
optimize and restore the vaginal ecosystem.
PMID- 27492696
TI - IFM (Intergroupe francophone du myelome) recommendations for uniform
interpretation of serum and urine protein electrophoresis in multiple myeloma
diagnosis and follow-up.
AB - Serum and urine proteins electrophoresis take a major place in multiple myeloma
management, at time of diagnosis, during follow-up for treatment response
evaluation and also in detection of relapse. The Intergroupe francophone du
myelome (IFM) suggests recommendations to clinicians and biologists, to perform
and interpret these biochemical analysis, with the objective of harmonizing
practices between laboratories and improving patients' follow-up.
PMID- 27492697
TI - Is it worth to report the presence of a single and additional band in the
cerebrospinal fluid detected by isoelectrofocusing?
AB - Despite the revisions of the Mac Donald criteria of multiple sclerosis (MS) in
2010, the cerebrospinal fluid (CSF) analysis by isoelectrofocusing (IEF) remains
useful for atypical presentations of MS. The IEF is considered as positive when
at least two or more additional bands are detected in the CSF by comparison with
the patient's serum but sometimes, the IEF interpretation is more difficult. The
goal of our study was to determine the significance when a single band in the CSF
is detected by IEF. We conducted a retrospective study on 990 patients who
underwent a lumbar puncture followed by a CSF analysis by IEF. Only 2% display
such IEF profile (i.e. single and additional band in the CSF). A diagnosis of
clinically isolated syndrome or MS was evidenced in 4 among those 21 patients. In
conclusion, our data suggest that even if the presence of a single and additional
band in the CSF is a rare situation, it should be mentioned to clinicians to not
exclude the hypothesis of an inflammatory demyelinating disease of the central
nervous system.
PMID- 27492698
TI - Next generation sequencing with a semi-conductor technology (Ion Torrent PGMTM)
for HLA typing: overall workflow performance and debate.
AB - Current high resolution HLA typing technologies produce ambiguous results, and it
is often necessary to perform additionnal tests to resolve these ambiguities.
Next generation sequencing is a promising technology, which can overcome this
problem. It is going to usher a new strategy to determine HLA compatibility
between donor and recipient. It can lead to non ambiguous results by analysing
the full amplified sequence of HLA genes and by eliminating heterozygote phase
ambiguities. Instead, as many new techniques, we can face several problems, such
as analysis difficulties because of incomplete HLA sequences in the database or
errors related to the sequencing instrumentation. Moreover, the clinical
relevance of analysing non coding regions of HLA genes is not well understood,
but raise questions about the interest of getting HLA full sequence to understand
drugs side effects or pathogenesis of infectious or auto-immune diseases. Our
objective in this article is to present a commercial workflow for HLA typing by
NGS, on Ion Torrent PGMTM sequencer, and to focus attention about pitfalls
encountered during the analysis.
PMID- 27492699
TI - PT, aPTT, TT and the hemostatic safety threshold of dabigatran and rivaroxaban.
AB - The proposals of the Working group on perioperative hemostasis (Groupe d'interet
en hemostase peri-operatoire (GIHP)) concerning the perioperative management of
patients receiving the direct oral anticoagulants (DOACs) are based on the
measure of their anticoagulant activities (anti-Xa for rivaroxaban and anti-IIa
for dabigatran) with a safety threshold <= 30 ng/mL. If the dosage of the drug is
not available, proposals are based on the combination of a PT >=80% and an aPTT
<=1.20. The aim of our study was to evaluate the performance of PT, aPTT and
thrombin time to predict values above or below the safety threshold. The
measurement of DOACs concentration was carried out in 64 samples from patients
treated with rivaroxaban and 48 samples from patients treated with dabigatran.
The PT and aPTT were measured for all samples, while the TT was measured only for
patients receiving dabigatran. The absence of agreement between the global
hemostasis tests and the DOACs concentrations was observed for 10% of patients
receiving dabigatran and 27% of patients with rivaroxaban treatment. Apart from
dabigatran for which the predictive negative value of PT and aPTT or TT allows to
exclude a concentration >30 ng/mL in 100% of cases, our results highlight the
risk of misinterpretation when using global coagulation tests (PT and aPPT) for
determination of the safety threshold for patients receiving the DOACs.
PMID- 27492700
TI - 24 hours calciuria: normal values, regulations: about a cohort of 317 control
subjects.
AB - In a control population, we filed the 24-hour urinary calcium to set normal
values, based on weight, BMI and menopause. By assessing calcium intake, 25OHD,
PTH, CTX, GFR, we wanted to study how these could influence calcium excretion. A
total of 317 subjects of 55.82 +/- 12.6 years were studied: 249 women (210 were
postmenopausal) and 66 men. Mean urinary calcium 24h was 4.07 +/- 2.53 mmol: 3.99
+/- 2.89 in men, 3.54 +/- 2.44 in premenopausal women, 4.18 +/- 2.42 in
postmenopausal women. 24-hour urine calcium was lower in overweight subjects
whether they are men or women. It was positively correlated to 25OHD, CTX, GFR,
serum calcium and negatively to PTH, BMI and weight. In conclusion, urinary
calcium was lower in overweight subjects, it increases after menopause. Dietary
calcium intake seems little involved in explaining variations in urinary calcium
which depends essentially on bone remodeling (CTX), GFR, levels of vitamin D and
PTH.
PMID- 27492701
TI - Isolated methylmalonic acidemia: a case report.
AB - Isolated methylmalonic acidemia (AMR) is an inborn error of metabolism due to an
enzymatic deficit in methylmalonyl-CoA mutase. AMR lead to increased
methylmalonic acid in plasma and urine without hyperhomocysteinemia. The clinical
signs are recurrent episodes of ketoacidosis and bouts of vomiting, dehydration
and mental retardation. These symptoms do not respond to the administration of
vitamin B12. We report a case of a ten-months-old infant to whom the diagnosis
was suspected in the presence of a metabolic acidosis, hyperammonemia, without
hepatic impairment and ketosis. The chromatography of organic acids showed
elevated methylmalonic acid levels. Molecular genetics allowed confirming the
diagnosis of deficit in methylmalonyl-CoA mutase demonstrating the genetic
abnormality of the gene MUT.
PMID- 27492702
TI - A paperless autoimmunity laboratory: myth or reality?
AB - Testing for antinuclear antibodies is the most frequently prescribed analysis for
the diagnosis of rheumatic diseases. Indirect immunofluorescence remains the gold
standard method for their detection despite the increasing use of alternative
techniques. In order to standardize the manual microscopy reading, automated
acquisition and interpretation systems have emerged. This publication enables us
to present our method of interpretation and characterization of antinuclear
antibodies based on a cascade of analyses and to share our everyday experience of
the G Sight from Menarini. The positive/negative discrimination on Hep cells 2000
is correct in 85% of the cases. In most of the false negative results, it is a
question of aspecific or low titers patterns, but a few cases of SSA speckled
patterns of low titers demonstrated a probability index below 8. Regarding the
pattern recognition, some types and mixed patterns are not properly recognized.
Concerning the probability index correlated in some studies to final titer, the
weak fluorescence of certain patterns and the random presence of artifacts that
distort the index don't lead us to continue it in our daily practice. In
conclusion, automated reading systems facilitate the reporting of results and
traceability of patterns but still require the expertise of a laboratory
technologist for positive/negative discrimination and for pattern recognition.
PMID- 27492704
TI - Immunoanalytical profile of androstenedione.
AB - Androstenedione is an androgen hormone and a precursor for testosterone and
estrone synthesis. It is produced in both gonadal (testes and ovaries) and
extragonadal levels (peripheral conversion of dehydroepiandrosterone). This
hormone is useful in the assessment of virilism and hirsutism in women. In this
paper, after a brief physiological reminder, the author presents the
preanalytical and analytical considerations and the clinical utility of this
hormone.
PMID- 27492703
TI - High fasting serum insulin level due to autoantibody interference in insulin
immunoassay discloses autoimmune insulin syndrome: a case report.
AB - Insulin-antibodies are a cause of misleading results in insulin immunoassays.
They may also mediate deleterious blood glucose variations. A patient presented
with overtiredness, recurrent episodes of sweating, dizziness and fainting fits.
A fasting serum insulin assay performed on a Modular platform (Modular analytic
E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7
mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other
immunometric insulin assays were performed, as well as antibodies anti-insulin
radiobinding assay (RBA) and gel filtration chromatography (GFC). While
complementary insulin assays yielded closer to normal fasting levels, the free
insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA
was positive. GFC revealed that most of the insulin was complexed with a 150 kDa
molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum
insulin level in a patient with neuroglucopenic symptoms was related to a high
insulin-antibody level, suggesting an insulin autoimmune syndrome.
PMID- 27492705
TI - Testez vos connaissances apres votre lecture.
PMID- 27492708
TI - Systematic characterization of polycrystalline silica-carbonate helices.
AB - Biomorphs are complex, life-like structures that emerge from the precipitation of
barium carbonate and amorphous silica in alkaline media. Despite their inorganic
nature, these microstructures have non-crystallographic morphologies such as
helices and cardioid sheets. At the nanoscale, biomorphs arrange thousands of
crystalline nanorods as hierarchical assemblies that resemble natural biominerals
suggesting novel approaches towards the production of biomimetic materials. We
report the synthesis of silica-carbonate biomorphs in single-phase, gradient-free
solutions that differ markedly from the typical solution-gas or gel-solution
setups. Our experimental approach significantly increases the duration of
biomorph growth and hence assembles networks in which individual helices extend
to several millimeters. These unusually long biomorphs allow the first
quantitative measurements of mesoscopic parameters such as the helix wavelength,
period, width, and linear as well as tangential growth velocities. We find that
the latter quantities are system-specific and tightly conserved during many hours
of growth. Moreover, the average double helix wavelength of (19 +/- 3) MUm and
width of (9.6 +/- 0.8) MUm vary by less than 12% when the initial carbonate
concentration is changed by three orders of magnitude. We also delineate the
single helix growth mechanism and report the occurrence of ribbon-like structures
and highly regular "superhelices". Our experiments clearly demonstrate the
robustness and consistency of biomorph growth under stable chemical conditions.
PMID- 27492707
TI - The molecular mechanism of thalidomide analogs in hematologic malignancies.
AB - Thalidomide was sold in the 1950s as a sedative and was also used by pregnant
women to treat morning sickness. It became notorious for causing severe birth
defects and was removed from the market. More than four decades later,
thalidomide had a renaissance in the treatment of cancer. Thalidomide and its
more potent analogs, lenalidomide and pomalidomide, are nowadays approved
treatments for multiple myeloma and myelodysplastic syndrome with deletion of
chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor
necrosis factor-alpha and increase interleukin-2 (IL-2) and interferon-gamma
release from T cells. The underlying molecular mechanisms for these pleiotropic
effects remained obscure until the identification of the cereblon (CRBN) E3
ubiquitin ligase as the primary target of thalidomide and its analogs in 2010.
Binding of thalidomide or lenalidomide increases the affinity of CRBN to the
transcription factors IKZF1 and IKZF3 and casein kinase 1alpha (CK1alpha).
Ubiquitination and degradation of these neo-substrates results in IL-2 release
and growth arrest of multiple myeloma and MDS cells. The discovery of this
previously undescribed mechanism for an approved drug provides a proof-of-concept
for the development of new therapeutics that exploit ubiquitin ligases for
specific degradation of disease-associated proteins.
PMID- 27492709
TI - Oblique rift opening revealed by reoccurring magma injection in central Iceland.
AB - Extension deficit builds up over centuries at divergent plate boundaries and is
recurrently removed during rifting events, accompanied by magma intrusions and
transient metre-scale deformation. However, information on transient near-field
deformation has rarely been captured, hindering progress in understanding rifting
mechanisms and evolution. Here we show new evidence of oblique rift opening
during a rifting event influenced by pre-existing fractures and two centuries of
extension deficit accumulation. This event originated from the Bardarbunga
caldera and led to the largest basaltic eruption in Iceland in >200 years. The
results show that the opening was initially accompanied by left-lateral shear
that ceased with increasing opening. Our results imply that pre-existing
fractures play a key role in controlling oblique rift opening at divergent plate
boundaries.
PMID- 27492706
TI - Oncolytic viruses-immunotherapeutics on the rise.
AB - The oncolytic virus (OV) field has entered an exciting period in its evolution in
which our basic understanding of viral biology and anti-cancer potential are
being actively translated into viable therapeutic options for aggressive
malignancies. OVs are naturally occurring or engineered viruses that are able to
exploit cancer-specific changes in cellular signaling to specifically target
cancers and their microenvironment. The direct cytolytic effect of OVs on cancer
cells is known to release antigens, which can begin a cascade of events that
results in the induction of anti-cancer adaptive immunity. This response is now
regarded as the most critical mechanism of OV action and harnessing it can lead
to the elimination of distant micrometastases as well as provide long-term anti
cancer immune surveillance. In this review, we highlight the development of the
OV field, why OVs are gaining an increasingly elevated standing as members of the
cancer immunotherapy armamentarium, and finally, ongoing clinical studies that
are aimed at translating unique OV therapies into approved therapies for
aggressive cancers.
PMID- 27492710
TI - Mechanistic Study on Gold-Catalyzed Highly Selective Hydroamination of
Alkylidenecyclopropanes.
AB - Density functional theory calculations have been carried out to study the
mechanism of the gold-catalyzed highly selective hydroamination of
alkylidenecyclopropanes. Two main mechanisms (i.e., double-bond activation-first
and three-membered-ring activation-first mechanisms) have been examined. The
double-bond activation-first mechanism results in the alkene hydroamination
product, and it mainly consists of three steps: C-N bond formation, C-C bond
rotation, and protodeauration (rate-determining step). Meanwhile, the three
membered-ring activation-first mechanism finally produces allylic amines, and it
occurs via the ring-opening (rate-determining step), C-N bond formation, and
protodeauration steps. The calculation results show good agreement with the
experimental outcomes on the chemo-, regio-, and diastereoselectivity. On this
basis, we found that the regioselectivity is caused by the C-C bond rotation
step, while the diastereoselectivity is determined by both the C-C bond rotation
and the protodeauration steps in the double-bond activation-first mechanism.
PMID- 27492711
TI - Double-balloon assisted trans-anal ERCP in a patient with Roux-en-Y
choledochojejunostomy.
PMID- 27492712
TI - Percutaneous transhepatic cholangioscopy for the diagnosis of biliary obstruction
in a patient with Roux-en-Y partial gastrectomy.
PMID- 27492713
TI - Successful treatment of a perforated duodenal ulcer with polyglycolic acid
sheets.
PMID- 27492714
TI - EUS-guided right hepatic bile duct drainage in complicated hilar stricture.
PMID- 27492716
TI - Rafael Alvarez Cordero, MD.
PMID- 27492715
TI - Cystic pancreatic neuroendocrine tumors: correlation of in vivo needle-based
confocal endomicroscopic findings by ex vivo analysis.
PMID- 27492717
TI - Exercise inducible laryngeal obstruction: diagnostics and management.
AB - Obstruction of the central airways is an important cause of exercise-induced
inspiratory symptoms (EIIS) in young and otherwise healthy individuals. This is a
large, heterogeneous and vastly understudied group of patients. The symptoms are
too often confused with those of asthma. Laryngoscopy performed as symptoms
evolve during increasing exercise is pivotal, since the larynx plays an important
role in symptomatology for the majority. Abnormalities vary between patients, and
laryngoscopic findings are important for correct treatment and handling. The
simplistic view that all EIIS is due to vocal cord dysfunction [VCD] still
hampers science and patient management. Causal mechanisms are poorly understood.
Most treatment options are based on weak evidence, but most patients seem to
benefit from individualised information and guidance. The place of surgery has
not been settled, but supraglottoplasty may cure well-defined severe cases. A
systematic clinical approach, more and better research and randomised controlled
treatment trials are of utmost importance in this field of respiratory medicine.
PMID- 27492718
TI - Epigallocatechin-3-gallate inhibits angiotensin II-induced C-reactive protein
generation through interfering with the AT1-ROS-ERK1/2 signaling pathway in
hepatocytes.
AB - Inflammation plays a key role in many chronic diseases such as cardiovascular
diseases and liver diseases. As a representative inflammatory molecule, C
reactive protein (CRP) is mainly produced in the liver. Hepatic CRP plays a
direct role in the inflammatory hepatic diseases and in development of
atherosclerosis when entering into the blood circulation. In the present study,
we observed the effect of epigallocatechin-3-gallate (EGCG) on Ang II-induced CRP
generation in hepatocytes and the molecular mechanism. Rats were delivered with
the subcutaneous infusion of Ang II and/or intragastric administration of EGCG
for 7 days. Hepatocytes were pretreated with EGCG before stimulation with Ang II
in vitro. CRP level in the serum and liver was determined with ELISA and the
immunohistochemical staining. RNA and protein expressions were determined using
RT-PCR and Western blot. The in vivo experiment confirmed that EGCG reduced not
only CRP generation in the liver of Ang II-infused rats but also serum CRP level.
The in vitro results showed that pretreatment of hepatocytes with EGCG inhibited
Ang II-induced mRNA and protein expression of CRP in a concentration-dependent
manner. Further study exhibited that EGCG downregulated AT1 expression,
attenuated Ang II-activated phosphorylation of ERK1/2, and upregulated Ang II
inhibited peroxisome proliferator-activated receptor gamma (PPARgamma) expression
in vitro and in vivo. In addition, EGCG decreased Ang II-stimulated reactive
oxygen species (ROS) generation in hepatocytes. These demonstrate that EGCG is
able to inhibit Ang II-induced CRP generation by interfering with AT1-ROS-ERK1/2
signal pathway in hepatocytes, which provides the new evidence and mechanism for
the anti-inflammatory effect of EGCG.
PMID- 27492719
TI - Identification of Limonol Derivatives as Heat Shock Protein 90 (Hsp90) Inhibitors
through a Multidisciplinary Approach.
AB - The identification of inhibitors of Hsp90 is currently a primary goal in the
development of more effective drugs for the treatment of various types of
multidrug resistant malignancies. In an attempt to identify new small molecules
modulating the activity of Hsp90, we screened a small library of
tetranortriterpenes. A high-affinity interaction with Hsp90 inducible form was
uncovered for eight of these compounds, five of which are described here for the
first time. By monitoring the ATPase activity and the citrate synthase thermal
induced aggregation, compound 1 (cedrelosin A), 3 (7alpha-limonylacetate), and 5
(cedrelosin B), containing a limonol moiety, were found to be the most effective
in compromising the Hsp90alpha chaperone activity. Consistent with these
findings, the three compounds caused a depletion of c-Raf and pAkt Hsp90 client
proteins in HeLa and MCF/7 cell lines. Induced fit docking protocol and molecular
dynamics were used to rationalize the structural basis of the biological activity
of the limonol derivatives. Taken together, these results point to limonol
derivatives as promising scaffolds for the design of novel Hsp90alpha inhibitors.
PMID- 27492720
TI - Dynamic expression of corticotropin-releasing hormone and urocortin in estrogen
induced-cholestasis pregnant rat.
AB - Intrahepatic cholestasis of pregnancy(ICP) is complicated by acute placental
fetal hypoxia. Corticotropin-releasing hormone(CRH) and urocortin(UCN) are
vasodilatory regulators of blood flow in the placenta. An ethinylestradiol(EE)
induced cholestasis rat model was reproduced and serum/placental CRH/UCN were
detected during 14-21days of gestation(DG). Maternal serum or placental CRH/UCN
levels in the control rats were relatively consistent during 14-21DG. Serum CRH
was reduced in the EE-treated rats compared with the control rats at 21DG.
Regarding serum UCN, we observed a decrease at 17DG as well as an increase at
21DG in the EE-treated rats compared with the controls. Moreover, we observed a
noticeable reduction of placental CRH/UCN expression at 17 or 19DG in the EE
treated rats compared with the control rats. The serum bile acids levels
exhibited an inverse correlation with placental CRH/UCN expression. EE-induced
cholestasis rats might serve as a good model to further investigate the
pathological mechanism underlying CRH/UCN dysregulation in ICP.
PMID- 27492721
TI - Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte
derived macrophages.
AB - Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential
regulators of inflammation which can be classified into two major vectors of
polarisation: classically activated macrophages (M1) and alternatively activated
macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and
M2-produced cytokines can have detrimental effects in development of diabetes
associated inflammation and diabetic vascular complications. However, the effect
of hyperglycaemia on differentiation and programming of primary human macrophages
was not systematically studied. We established a unique model to assess the
influence of hyperglycaemia on M1 and M2 differentiation based on primary human
monocyte-derived macrophages. The effects of hyperglycaemia on the gene
expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and
prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA.
Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during
macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute,
while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression
of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted
levels remained to be biologically significant. Our data indicate that
hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2
cytokine profile that can support of diabetes-associated inflammation and
development of vascular complications.
PMID- 27492722
TI - The Masters of the Bolognese Orthopaedic School.
AB - Bologna is one of the most ancient cradles of medical knowledge, as the city
hosts one of the oldest medical faculties in the world. Among its best known
institutions there is the Rizzoli Orthopaedic Institute, founded in the late
nineteenth century, whose history is strictly connected with the evolution and
development of the Italian orthopaedic practice of the last 120 years. The
present manuscript acknowledges the main contributions by Francesco Rizzoli,
Alessandro Codivilla and Vittorio Putti, who prompted the foundation and the
international recognition of the Rizzoli Institute and the related Bolognese
Orthopaedic School.
PMID- 27492723
TI - Reliability of measurements performed on two dimensional and three dimensional
computed tomography in glenoid assessment for instability.
AB - PURPOSE: The main purpose of this study is to establish which of two methods is
more reliable in glenoid assessment for instability in pre-operative planning.
Accordingly, we have studied the intra- and inter-observer reliability of glenoid
parameters with the use of two-dimensional (2D) and three-dimensional (3D)
reconstructed computed tomography (CT) images. METHODS: One hundred glenoids were
measured with the use of 2D-CT and 3D-CT (in 3D orientation) by two independent
observers (one experienced and one inexperienced). Measurements were repeated
after one week for 30 randomly selected glenoids. RESULTS: The intra-class
correlation coefficient (ICC) for inter-observer reliability was significantly
greater for 3D-CT (0.811 to 0.915) than for 2D-CT (0.523 to 0.925). All intra
observer reliability values for 3D-CT were near perfect (0.835 to 0.997), while
those for 2D-CT were less reliable (0.704 to 0.960). A dependent t-test showed
that, for both observers, almost all glenoid parameters (except R and d) differed
significantly (p < 0.05) between 2D and 3D measurement methods. CONCLUSIONS:
Therefore, it can be concluded that 3D glenoid reconstructions are more reliable
for glenoid bone loss assessment than 2D-CT. The results suggest that quantifying
a glenoid defect with the use of 2D image only-even if performed by an
experienced orthopaedic surgeon-is prone to errors. Differences in measurements
between and within observers can be explained by plane setting and identifying
glenoid rim in 2D-CT. Accordingly, we recommend that glenoid measurements should
be performed in 3D orientation using 3D reconstruction obtained from CT images
for pre-operative assessments, which are crucial for surgical planning.
PMID- 27492724
TI - Tetanus toxin production is triggered by the transition from amino acid
consumption to peptides.
AB - Bacteria produce some of the most potent biomolecules known, of which many cause
serious diseases such as tetanus. For prevention, billions of people and
countless animals are immunised with the highly effective vaccine, industrially
produced by large-scale fermentation. However, toxin production is often hampered
by low yields and batch-to-batch variability. Improved productivity has been
constrained by a lack of understanding of the molecular mechanisms controlling
toxin production. Here we have developed a reproducible experimental framework
for screening phenotypic determinants in Clostridium tetani under a process that
mimics an industrial setting. We show that amino acid depletion induces
production of the tetanus toxin. Using time-course transcriptomics and
extracellular metabolomics to generate a 'fermentation atlas' that ascribe growth
behaviour, nutrient consumption and gene expression to the fermentation phases,
we found a subset of preferred amino acids. Exponential growth is characterised
by the consumption of those amino acids followed by a slower exponential growth
phase where peptides are consumed, and toxin is produced. The results aim at
assisting in fermentation medium design towards the improvement of vaccine
production yields and reproducibility. In conclusion, our work not only provides
deep fermentation dynamics but represents the foundation for bioprocess design
based on C. tetani physiological behaviour under industrial settings.
PMID- 27492725
TI - Calcium hydroxyapatite crystal deposition with intraosseous penetration involving
the posterior aspect of the cervical spine: a previously unreported cause of neck
pain.
AB - PURPOSE: Calcific tendinitis is a frequent disorder caused by hydroxyapatite
crystal deposition; however, bone erosions from calcific tendinitis are unusual.
The spinal manifestation of this disease is calcific tendinitis of the longus
colli muscle; this disease has never been described in the posterior aspect of
the spine. We report a case of calcium hydroxyapatite crystal deposition
involving the posterior cervical spine eroding the bone cortex. METHODS: A 57
year-old woman presented with a 5-month history of left-sided neck pain.
Radiographs showed C4-C5 interspinous calcification with lytic compromise of the
posterior arch of C4. Magnetic resonance imaging confirmed a lytic lesion of the
posterior arch of C4, with a soft tissue mass extending to the C4-C5 interspinous
space; calcifications were observed as very low signal intensity areas on T1 and
T2 sequences, surrounded by gadolinium-enhanced soft tissues. A computed
tomography (CT) scan confirmed the bone erosions and the soft tissue
calcifications. RESULTS: A CT-guided needle biopsy was performed; it showed
vascularized connective tissue with inflammatory histiocytic infiltration and
multinucleated giant cells; Alizarin Red stain confirmed the presence of
hydroxyapatite crystals. The patient was treated with anti-inflammatories for 2
weeks. She has been asymptomatic in a 6-month follow-up; a CT scan at the last
follow-up revealed reparative remodeling of bone erosions. CONCLUSION: This is
the first report of calcium hydroxyapatite crystal deposition with intraosseous
penetration involving the posterior aspect of the cervical spine. Considering
that this unusual lesion can be misinterpreted as a tumor or infection, high
suspicion is required to avoid unnecessary surgical procedures.
PMID- 27492726
TI - HIV Infection and Myocardial Infarction.
AB - BACKGROUND: After the advent of the potent combination antiretroviral therapy
(cART) the incidence of acquired immune deficiency syndrome (AIDS) has declined
dramatically and HIV infection became a chronic disease with a significant
increase in the life expectancy of HIV-positive people. Consequently, chronic
comorbidities as coronary heart disease raised an increasing concern in this
population. OBJECTIVE: Aim of this editorial article is to review the most recent
data about the cardiovascular disease risk among HIV-positive persons and to
suggest an appropriate clinical management. RESULTS: An increased risk of
myocardial infarction has been reported among HIVinfected subjects compared to
the general population, but the pathogenic mechanism of this accelerated
atherosclerotic process is complex and certainly multifactorial. The occurrence
of myocardial infarction may be the consequence of traditional risk factors (that
are overrepresented in the HIVinfected population), direct viral replication, and
long-term toxicity of the antiretroviral drugs. Moreover, despite the persistent
viral suppression induced by cART usually reduces the cardiovascular risk,
several studies show in HIV-positive subjects a condition of chronic inflammation
and immune activation that could lead to both accelerated endothelial dysfunction
and atherosclerotic disease. CONCLUSION: The cardiovascular risk reduction and
coronary heart disease prevention are today a leading challenge for all the
clinicians involved in the HIV patients' care.
PMID- 27492727
TI - Spatiotemporal Analysis of AIDS Incidence Among Adults in Brazil.
AB - : AIDS is the fourth leading cause of death worldwide and, currently, the overall
prevalence rate of HIV infection in Brazil is 0.5% among men and 0.3% among
women. OBJECTIVE: To evaluate the spatiotemporal trend of AIDS in Brazil from
2006 to 2012 and its relationship with human development index (HDI) and their
components income, education and life expectancy. METHODS: This ecological study
evaluate the spatiotemporal trend of standardized incidence ratio of AIDS among
adults in Brazil from 2006 to 2012 and its relationship with HDI by using a
Bayesian analysis, considering the Brazilian Federal Units as units of analysis.
The proposed statistical model allows obtaining a standardized incidence ratio
(SIR, adjusted by gender and age). RESULTS: Among the men, our results show
higher incidence rates in the States of the Southern regions as well as in the
state of Amazonas (Northern Brazil). In females, we found other patterns for SIR,
with higher incidence rates in the states of Rio de Janeiro (Southeast region),
Rio Grande do Sul and Santa Catarina (both in Southern region). Among men it was
observed as an expressive association between the SIR values and the overall HDI
and income and education components, but it was observed to have an inverse
association with the life expectancy component. Among women, it is noted that the
SIR values are associated with the overall HDI and the education components only
at the beginning of the studied period. DISCUSSION: AIDS remains a major public
health problem in Brazil, mainly in the southern and southeastern regions of the
country. Considering its association with HDI, it is noted that the disease still
remains related to the pattern observed in the early years of the studied period,
at least in the more developed regions of Brazil. This certainly happened because
of the chronicity of the disease, thus affecting people with good socioeconomic
status.
PMID- 27492728
TI - The lasso-loop, lasso-mattress and simple-cinch stitch for arthroscopic rotator
cuff repair: are there biomechanical differences?
AB - PURPOSE: Various stitching techniques have been described to facilitate
arthroscopic repair of rotator cuff tears. The aim of the present study was to
compare the biomechanical properties of the lasso-loop, lasso-mattress and simple
cinch stitch for rotator cuff repair. METHODS: Twelve infraspinatus tendons were
harvested from sheep and split in half. The tendons were randomized into three
different stitch configuration groups for biomechanical testing: lasso-loop,
lasso-mattress and simple-cinch stitch. Each specimen was first cyclically loaded
on a universal materials testing machine under force control from 5 to 30 N at
0.25 Hz for twenty cycles. Then, each specimen was loaded to failure under
displacement control at a rate of 1 mm/s. Cyclic elongation, peak-to-peak
displacement and ultimate tensile load were reported as mean +/- standard error
and compared using one way analysis of variance. The type of failure was
recorded. RESULTS: No differences in cyclic elongation (1.31 +/- 0.09 mm for the
simple-cinch vs. 1.49 +/- 0.07 mm for the lasso-mattress vs. 1.61 +/- 0.09 mm for
the lasso-loop stitch, p = 0.063) or peak-to-peak displacement (0.58 +/- 0.04 mm
for the simple-cinch, 0.50 +/- 0.03 mm for the lasso-mattress and 0.62 +/- 0.06
mm for the lasso-loop stitch, p = 0.141) were seen between all tested stitch
configurations. In the load-to-failure test, the simple cinch stitch (149.38 +/-
11.89 N) and the lasso-mattress (149.38 +/- 10.33 N) stitch demonstrated
significantly higher ultimate load than the lasso-loop stitch (65.88 +/- 4.75 N,
p < 0.001). All stitch configurations failed with suture pull out. CONCLUSIONS:
The lasso-mattress and the simple-cinch stitch showed similar biomechanical
properties with significant higher tensile loads needed for failure than the
lasso-loop stitch.
PMID- 27492729
TI - Surgically induced changes in retinal vessel diameter, retinal nerve fibre layer
thickness, and the optic disc after 23-gauge pars plana vitrectomy.
AB - The aim of the study is to investigate the retinal vascular calibre, retinal
nerve fibre layer's thickness, and optic disc changes in patients after pars
plana vitrectomy. We examined 40 eyes in 40 patients who had undergone unilateral
pars plana vitrectomy at three time points: prior to surgery, and at 3 and 6
months after the operation. The diameters of central retinal arteries and veins
were measured using retinal photographs. The central retinal arteriolar
equivalent (CRAE) and central retinal venular equivalent (CRVE) were calculated
using the revised Parr-Hubbard formula. Retinal nerve fibre layer thickness was
obtained using Stratus optical coherence tomography. The cup-to-disc vertical
ratio of the optic disc was evaluated using stereo optic disc photography. There
were no significant differences between the eyes of individual patients before
the operation. Cup-to-disc vertical ratios of the optic disc were significantly
increased 3 and 6 months postoperatively (p < 0.01, p < 0.01), and there was a
significant difference between the operative eye and fellow eye at the same time
points (p < 0.01, p < 0.01). Changes in CRAE and CRVE in the operative eyes were
significantly larger than the fellow eyes 6 months postoperatively (p < 0.01, p <
0.01). The retinal nerve fibre layer thickness showed no significant changes.
While there were no changes in retinal nerve fibre layer thickness, vitrectomy
induced changes in the cup-to-disc vertical ratio of the optic disc and retinal
vessel diameter for at least 6 months after surgery.
PMID- 27492730
TI - Incidence and risk factors associated with retinal redetachment after silicone
oil removal in the African population.
AB - The purpose of this study was to investigate the incidence and risk factors
associated with retinal redetachment after silicone oil (SO) removal in the
African population. A retrospective cohort study was performed on patients
undergoing SO removal over a period of 4 years. The risk factors assessed were
(1) characteristics of the retinal detachments including type of retinal
detachment, type, number and location of the retinal tears, and proliferative
vitreoretinopathy (PVR) score, and (2) surgical factors including type of
silicone oil used, use of laser prior to SO removal, and location of the laser
(360 degrees or around the tear only). SO was removed either through a pars
plana approach or transpupillary approach and anterior limbal incision. Ninety
nine eyes met the inclusion criteria during the study period. Twelve patients (12
%) had retinal redetachment after SO removal. Factors associated with
redetachment were a preexisting macular hole, PVR grade B or worse, and no
intraoperative endolaser photocoagulation. The incidence of redetachment in
African population is similar to that reported from developed countries and other
advanced vitreoretinal centers. Redetachment occurred at higher rates in patients
with preexisting macular holes and tears who did not receive intraoperative
endolaser photocoagulation and patients with a severe grade of PVR.
PMID- 27492731
TI - Retina ganglion cell/inner plexiform layer and peripapillary nerve fiber layer
thickness in patients with acromegaly.
AB - Increased secretion of growth hormone and insulin-like growth factor-1 in
acromegaly has various effects on multiple organs. However, the ocular effects of
acromegaly have yet to be investigated in detail. The aim of the present study
was to compare retina ganglion cell/inner plexiform layer (GCIPL) and
peripapillary nerve fiber layer thickness (pRNFL) between patients with
acromegaly and healthy control subjects using spectral domain optical coherence
tomography (SD-OCT). This cross-sectional, comparative study included 18 patients
with acromegaly and 20 control subjects. All participants underwent SD-OCT to
measure pRNFL (in the seven peripapillary areas), GCIPL (in the nine ETDRS
areas), and central macular thickness (CMT). Visual field (VF) examinations were
performed using a Humphrey field analyzer in acromegalic patients. Measurements
were compared between patients with acromegaly and control subjects. A total of
33 eyes of 18 patients with acromegaly and 40 eyes of 20 control subjects met the
inclusion criteria of the present study. The overall calculated average pRNFL
thickness was significantly lower in patients with acromegaly than in control
subjects (P = 0.01), with pRNFL thickness significantly lower in the temporal
superior and temporal inferior quadrants. Contrary to our expectations, pRNFL
thickness in the nasal quadrant was similar between acromegalic and control
subjects. The mean overall pRNFL thickness and superonasal, nasal, inferonasal,
and inferotemporal quadrant pRNFL thicknesses were found to correlate with the
mean deviation (MD) according to Spearman's correlation. However, other quadrants
were not correlated with VF sensitivity. No significant difference in CMT values
was observed (P = 0.6). GCIPL thickness was significantly lower in all quadrants
of the inner and outer macula, except for central and inferior outer quadrants,
in the acromegaly group than that in the control group (P < 0.05). GCIPL
thicknesses of the inferior inner and outer macula quadrants were found to
correlate with MD, whereas no correlation was observed between other quadrants
and VF sensitivity. We demonstrated that GCIPL thickness decreased in patients
with acromegaly compared with that in control subjects. However, the nasal
quadrant pRNFL thickness was similar in acromegaly, in contrast to our
expectations. SD-OCT may have utility in the assessment of the effects of
acromegaly on retinal structures.
PMID- 27492732
TI - Charlson comorbidity index predicts poor outcome in CML patients treated with
tyrosine kinase inhibitor.
AB - Although the Sokal and Hasford scoring systems are well-known prognostic models
specific to chronic myeloid leukemia (CML), whether they can effectively predict
outcomes in elderly CML patients with comorbidities has not been fully
elucidated. We evaluated the association between comorbidity at diagnosis with
treatment outcome and survival in chronic phase CML patients. A questionnaire was
administered to patients diagnosed with CML between 2001 and 2012 and treated
with tyrosine kinase inhibitors (TKIs). The Charlson comorbidity index (CCI) was
used to determine concomitant diseases. In total, 79 patients (33 females; median
age, 57 years) were enrolled. CCI scores at diagnosis were between 2 and 11. At
the last follow-up, 46 patients showed a major molecular response. Complete
cytogenetic response was achieved in 73.4 % of the cases 12 months after TKI
administration. We observed only five deaths during the 55.5-month median follow
up period. The risk categories (low/intermediate/high) associated with Sokal and
Hasford scores were 33/27/7 and 21/43/3, respectively. The 27 cases with a CCI
score >3 had significantly poorer survival after diagnosis (52 cases had a CCI
score <2). CCI scores were inversely associated to overall survival. Concomitant
comorbidity at diagnosis is associated with poor outcome in CML patients treated
with TKIs.
PMID- 27492733
TI - Dosing of loop diuretics in chronic heart failure: it's time for evidence.
PMID- 27492734
TI - 3D printing of an interpenetrating network hydrogel material with tunable
viscoelastic properties.
AB - Interpenetrating network (IPN) hydrogel materials are recognized for their unique
mechanical properties. While IPN elasticity and toughness properties have been
explored in previous studies, the factors that impact the time-dependent stress
relaxation behavior of IPN materials are not well understood. Time-dependent
(i.e. viscoelastic) mechanical behavior is a critical design parameter in the
development of materials for a variety of applications, such as medical
simulation devices, flexible substrate materials, cellular mechanobiology
substrates, or regenerative medicine applications. This study reports a novel
technique for 3D printing alginate-polyacrylamide IPN gels with tunable elastic
and viscoelastic properties. The viscoelastic stress relaxation behavior of the
3D printed alginate-polyacrylamide IPN hydrogels was influenced most strongly by
varying the concentration of the acrylamide cross-linker (MBAA), while the
elastic modulus was affected most by varying the concentration of total monomer
material. The material properties of our 3D printed IPN constructs were
consistent with those reported in the biomechanics literature for soft tissues
such as skeletal muscle, cardiac muscle, skin and subcutaneous tissue.
PMID- 27492735
TI - Biopsychosocial predictors of coping strategies of patients postmyocardial
infarction.
AB - Data from the Patients and Families Psychological Response to the Home Automated
External Defibrillator Trial were used to examine the relationship between
biopsychosocial variables and patients' coping strategies postmyocardial
infarction. This study is the secondary data analysis of longitudinal
observational study. A total of 460 patient-spouse pairs were recruited in
January 2003 to October 2005. Hierarchical linear regression analysis examined
biological/demographic, psychological and social variables regarding patients'
coping scores using the Family Crisis Oriented Personal Evaluation Scale. Lower
social support and social support satisfaction predicted lower total coping
scores. Being younger, male gender and time since the myocardial infarction
predicted lower positive coping strategy use. Higher anxiety and lower social
support were related to fewer positive coping methods. Lower educational levels
were related to increased use of negative coping strategies. Reduced social
support predicted lower total coping scores and positive coping strategy use and
greater passive coping style use. Social support from a broad network assisted
with better coping; those living alone may need additional support. Social
support and coping strategies should be taken into consideration for patients who
have experienced a cardiac event.
PMID- 27492736
TI - In vivo evaluation of shark teeth-derived bioapatites.
AB - OBJECTIVE: The present work proposes the shark teeth as a new source of
bioapatites for bone filler applications in maxillary sinus elevation,
periodontal regeneration or implants placement. This abundant fishing by-product
provides an improved hydroxyapatite (HA) with fluorine contributions. The in vivo
evaluation of osteointegration and bone mineral density levels promoted by these
marine bioapatites was the main objective. MATERIALS AND METHODS: Marine
bioapatite granules of two sizes (1 mm, <20 MUm) were obtained and characterized
(XRD, SEM, ICP-OES) to determine morphology and composition. In vivo evaluation
was performed, after bioapatites implantation in critical defects of parietal
bone of 25 rats, for 3 weeks. Commercial synthetic HA/betaTCP (60/40%) material
and unfilled defects were used as controls. Radiology, micro-CT, histology and
quantification of bone mineral density are presented. RESULTS: These marine
bioapatites presented a globular porous morphology. A biphasic composition ~70%
apatitic (HA, apatite-CaF, fluorapatite) and ~30% non-apatitic phase
(whitlockite, tricalcium bis(orthophosphate)), with contributions of F (1.0 +/-
0.5%wt), Na (0.9 +/- 0.2%wt) and Mg (0.65 +/- 0.04%wt) was confirmed. After
implantation period, higher osteointegration of 1-mm marine bioapatites than
commercial synthetic granules was observed, together with bone formation from the
defect surroundings but also at central area (potential osteoinductive
properties). New bone cells penetrated inside pores and inter-granular cavities.
Higher bone mineral density, in both 1-mm and <20-MUm granules, than on
commercial synthetic graft was determined, being significant in 1-mm bioapatites
(a P < 0.05). CONCLUSION: Shark teeth bioapatites were successfully validated as
new functionally efficient bone filler in rat model, promoting significantly
increased bone mineral density than synthetic control.
PMID- 27492737
TI - Characterization of Acr2, an H-NS-like protein encoded on A/C2-type plasmids.
AB - Conjugation plays an important role in the horizontal movement of DNA between
bacterial species and even genera. Large conjugative plasmids in Gram-negative
bacteria are associated with multi-drug resistance and have been implicated in
the spread of these phenotypes to pathogenic organisms. A/C plasmids often carry
genes that confer resistance to multiple classes of antibiotics. Recently,
transcription factors were characterized that regulate A/C conjugation. In this
work, we expanded the regulon of the negative regulator Acr2. We developed an A/C
variant, pARK01, by precise removal of resistance genes carried by the plasmid in
order to make it more genetically tractable. Using pARK01, we conducted RNA-Seq
and ChAP-Seq experiments to characterize the regulon of Acr2, an H-NS-like
protein. We found that Acr2 binds several loci on the plasmid. We showed, in
vitro, that Acr2 can bind specific promoter regions directly and identify key
amino acids which are important for this binding. This study further
characterizes Acr2 and suggests its role in modulating gene expression of
multiple plasmid and chromosomal loci.
PMID- 27492738
TI - Impact of the implementation of an evidence-based guideline on diagnostic
testing, management, and clinical outcomes for infants with bronchiolitis.
AB - BACKGROUND: Although bronchiolitis poses a significant health problem in low- and
middle-income countries (LMICs), to the best of our knowledge, to date it has not
been determined whether evidence-based bronchiolitis clinical practice guidelines
(CPGs) complemented by standardized educational strategies reduce the use of
unnecessary diagnostic tests and medications and improve clinically important
outcomes in LMICs. METHODS: In an uncontrolled before and after study, we
assessed the impact of the implementation of an evidence-based bronchiolitis CPG
on physician behavior and the care of infants with bronchiolitis by comparing pre
guideline (March to August 2014) and post-guideline (March to August 2015) use of
diagnostic tests and medications through an electronic medical record review in a
children's hospital in Bogota, Colombia. We also sought to assess the impact of
the implementation of the CPG on clinically important outcomes such as lengths of
stay, hospital admissions, intensive care admissions, and hospital readmissions.
RESULTS: Data from 662 cases of bronchiolitis (pre-guideline period) were
compared with the data from 703 cases (post-guideline period). On comparing the
pre- and post-guideline periods, it was seen that there was a significant
increase in the proportion of patients with an appropriate diagnosis and
treatment of bronchiolitis (36.4% versus 44.5%, p = 0.003), and there were
statistically significant decreases in the use of a hemogram (33.2% versus 26.6%,
p=0.010), procalcitonin (3.9% versus 1.6%, p=0.018), nebulized beta-2 agonists
(45.6% versus 3.4%, p < 0.001), nebulized anticholinergics (3.3% versus 1.4%, p=
0.029), and nebulized epinephrine (16.2% versus 7.8%, p < 0.001). Likewise, a
significant increase in the use of nebulized hypertonic saline was seen (79.6%
versus 91.7%, p < 0.001). However, implementation of the CPG for bronchiolitis
was not associated with significant changes in clinically important outcomes.
CONCLUSIONS: The development and implementation of a good quality bronchiolitis
CPG is associated with a significant increase in the proportion of cases with an
appropriate diagnosis and treatment of the disease in the context of a university
based hospital located in the capital of an LMIC. However, we could not
demonstrate an improvement in clinically important outcomes such as any of the
bronchiolitis severity parameters.
PMID- 27492740
TI - New repellent effective against African malaria mosquito Anopheles gambiae:
implications for vector control.
AB - Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) is a vector for
Plasmodium, the causative agent of malaria. Current control strategies to reduce
the impact of malaria focus on reducing the frequency of mosquito attacks on
humans, thereby decreasing Plasmodium transmission. A need for new repellents
effective against Anopheles mosquitoes has arisen because of changes in vector
behaviour as a result of control strategies and concern over the health impacts
of current repellents. The response of A. gambiae to potential repellents was
investigated through an electroantennogram screen and the most promising of these
candidates (1-allyloxy-4-propoxybenzene, 3c{3,6}) chosen for behavioural testing.
An assay to evaluate the blood-host seeking behaviour of A. gambiae towards a
simulated host protected with this repellent was then performed. The compound
3c{3,6} was shown to be an effective repellent, causing mosquitoes to reduce
their contact with a simulated blood-host and probe less at the host odour. Thus,
3c{3,6} may be an effective repellent for the control of A. gambiae.
PMID- 27492739
TI - Effect of selective serotonin reuptake inhibitors use on endocrine therapy
adherence and breast cancer mortality: a population-based study.
AB - The purpose of the study was to investigate whether the concomitant use of
selective serotonin reuptake inhibitors (SSRI) with tamoxifen influences the risk
of death due to breast cancer, and we also investigated the association between
SSRI use and adherence to oral endocrine therapy (ET). We analyzed data from
BCBaSe Sweden, which is a database created by the data linkage of Registries from
three different regions of Sweden. To investigate the association between ET
adherence and SSRI use, we included all women who were diagnosed with non-distant
metastatic ER-positive invasive breast cancer from July 2007 to July 2011 and had
at least one dispensed prescription of oral tamoxifen or aromatase inhibitor. To
investigate the role of concurrent administration of SSRI and tamoxifen on breast
cancer prognosis, we performed a nested case-control study. In the adherence
cohort, 9104 women were included in the analyses. Women who received SSRI, either
before or after breast cancer diagnosis, were at higher risk for low adherence to
ET. However, when the overlapping period between SSRI use and ET was >50 %, no
excess risk for low adherence was observed. Non-adherence (<80 %) to ET was
significantly associated with worse breast cancer survival (OR 4.07; 95 % CI 3.27
5.06). In the case-control study, 445 cases and 11125 controls were included. The
concomitant administration of SSRI and tamoxifen did not influence breast cancer
survival, neither in short-term (OR 1.41; 95 % CI 0.74-2.68) nor in long-term
SSRI users (OR 0.85; 95 % CI 0.35-2.08). Concomitant SSRI and tamoxifen use does
not seem to increase risk for death due to breast cancer. Given the positive
association between continuing antidepressive pharmacotherapy for a longer period
of time and adherence to ET, it is essential to capture and treat depression in
breast cancer patients to secure adherence to ET.
PMID- 27492741
TI - Effect of Repetitive Intracutaneous Injections with Local Anesthetics and
Steroids for Acute Thoracic Herpes Zoster and Incidence of Postherpetic
Neuralgia.
AB - Background: Treatment of established postherpetic neuralgia (PHN) is difficult
and often disappointing. In this study, we assessed the efficacy of repetitive
intracutaneous injections with local anesthetics and steroids in acute thoracic
herpes zoster (HZ) pain, herpetic eruption, and incidence of PHN. Methods: Ninety
three patients with acute thoracic HZ were randomly assigned to receive a
standard treatment of antiviral medication with p.o. analgesics or the standard
treatment with the addition of repetitive intracutaneous injections of a local
anesthetic and steroid mixture. Patients were permitted to take tramadol when the
visual analog scale (VAS) >= 4. Pain assessment using VAS was conducted at the
initial visit, as well as 1, 2, 4, 12, and 24 weeks after the end of the
treatments. Results: In comparison with the standard treatment group, the VAS
scores of the intracutaneous injection group were significantly lower during the
study. The intracutaneous injection group also reported shorter duration of pain
and skin eruption than the control group ( P = 0.005 vs P < 0.001,
respectively). At 1 month post-therapy, 12.8% patients in the intracutaneous
injection group reported zoster-associated pain, compared with 47.8% in the
standard treatment group ( P < 0.001). At 3 and 6 months post-therapy, the
incidence of PHN was still significantly lower in the intracutaneous injection
group than the standard treatment group. EuroQol VAS scores were significantly
higher in the intracutaneous injection group vs standard treatment group (P <
0.001). Conclusion: Repetitive intracutaneous injections with local anesthetics
and steroids along with standard treatment significantly reduce the duration of
pain and herpetic eruption and incidence of PHN.
PMID- 27492742
TI - A Different Approach to the Management of Osteoarthritis in the Knee: Ultrasound
Guided Genicular Nerve Block.
PMID- 27492743
TI - Psychological Treatment Needs for Chronic Pain in Singapore and the Relevance of
the Psychological Flexibility Model.
AB - Objective: The goals of the present study were (a) to assess the psychological
treatment needs and treatment delivery preferences in people attending services
or contacting a hospital website for chronic pain in Singapore, and (b) to
explore potential relevance of the psychological flexibility (PF) model for this
group by investigating associations between PF and pain-related outcomes. Design
and Setting: This was a cross-sectional questionnaire study of people with
chronic pain in Singapore. Subjects: Current users of treatment services at a
tertiary pain management clinic (PMC), users of pain treatment services
elsewhere, and non-treatment users. Methods: Participants were either recruited
face-to-face at a pain clinic or via an online portal. All participants completed
a questionnaire, including a survey of treatment barriers and needs, treatment
delivery preferences for chronic pain, and standardized measures of PF, pain
interference, emotional functioning, and health care use. Results: A total of 200
participants completed the study. Cost of treatment was identified as a main
deterrent, while proof of treatment success was identified as a main facilitator
for treatment uptake. A majority of participants (88.5%) indicated a preference
for face-to-face treatment. In multiple regression analyses, after controlling
for relevant demographic variables and pain intensity, PF explained 14% of the
variance for pain interference and impact of depressive symptoms and 22% of the
variance for depressive symptoms. Conclusion: A focus on meeting patients' needs
at low cost, and providing proof of treatment success may increase psychological
treatment uptake. Increasing PF for pain in people from Singapore may also
contribute to better patient functioning.
PMID- 27492744
TI - Acid-triggered release of doxorubicin from a hydrazone-linked Gd(3+)-texaphyrin
conjugate.
AB - The hydrazone-based Gd(3+)-texaphyrin doxorubicin conjugate 1, releases active
doxorubicin at acidic pH values, allowing its components to be followed by two
complementary imaging methods, namely Off-On fluorescence enhancement and MR
imaging. It thus acts as a promising theranostic agent.
PMID- 27492745
TI - A multidisciplinary approach to prenatal treatment of congenital long QT
syndrome.
AB - A 27-week fetus evaluated for bradycardia and hydrops was found to have anti-SSA
negative 2 degrees atrioventricular block and ventricular tachycardia. A
presumptive diagnosis of fetal long QT syndrome was made. Transplacental
pharmacotherapy with intravenous magnesium and lidocaine restored sinus rhythm.
At 30 6/7 weeks, the infant was delivered due to premature labor. Despite
postnatal treatment with mexiletine and propranolol, she developed torsades de
pointes. Ultimately, a de novo KCNH2 G628S mutation was diagnosed. She received
an implantable cardiac defibrillator at 5 months of age. Early diagnosis and a
multidisciplinary approach allowed successful in utero treatment and anticipatory
postnatal management. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:168
170, 2017.
PMID- 27492746
TI - [Management of symptoms associated with spasticity in patients with multiple
sclerosis].
AB - OBJECTIVE: To describe the role of nurses in the management of symptoms related
to spasticity in patients with multiple sclerosis (MS). METHOD: A descriptive
study was developed based on a questionnaire on spasticity in MS patients. The
questionnarie was completed through an anonymous tele-voting system at a national
meeting with nurses involved in the management of these patients. RESULTS: Apart
from fatigue, according to the opinion of the participants, the spasticity
symptom associated with MS most notified by patients was difficulty in walking,
followed by spasms and pain. Participants thought that it is important that
nursing takes: 1) a role in identifying these symptoms, 2) should focus on the
detection of the triggering or aggravating factors, and 3) on providing support
in the assessment of the level of spasticity. It is important to inform about the
correct use of anti-spasticity drugs, how to adjust the dosage and side effects
of treatments, including cannabinoids via an oromucosal spray, titrating its
doses according to each patient, and monitoring its tolerability, efficacy and
adherence. Although there are usually resources to follow up these patients,
there are still important gaps, including the lack of a specific follow-up
protocol. CONCLUSIONS: Although all the participants are experts in the
management of patients with MS, there is still diversity in the functions they
perform, and the available resources they have in their hospitals. Nurses act as
a key element in the process of identification of symptoms, training and
monitoring of these patients with spasticity in EM.
PMID- 27492748
TI - Simple Approach to Synthesize Amino-Functionalized Carbon Dots by Carbonization
of Chitosan.
AB - Carbon dots (CDs) as a new series of fluorescent nanomaterials have drawn great
attention in recent years owning to their unique properties. In this paper, a
simple carbonization approach to synthesize amino-functionalized CDs was
developed by using chitosan as the carbon precursor. The as-prepared CDs
possessed desirable amino function group on their surface and exhibited bright
luminescence with absolute quantum yield (QY) of 4.34%, excitation-, pH-dependent
and up-conversion fluorescence behaviors. Furthermore, we have investigated the
cytotoxicity and biocompatibility of the as-prepared CDs, which demonstrated that
the as-prepared CDs have the potential applications in biosensing, cellular
imaging and drug delivery.
PMID- 27492747
TI - Loss of Major DNase I Hypersensitive Sites in Duplicated beta-globin Gene Cluster
Incompletely Silences HBB Gene Expression.
AB - We report an infant with sickle cell disease phenotype by biochemical analysis
whose beta-globin gene (HBB) sequencing showed sickle cell mutation (HBBS )
heterozygosity. The proband has a unique head-to-tail duplication of the beta
globin gene cluster having wild-type (HBBA ) and HBBS alleles inherited from her
father; constituting her HBBS /HBBS -HBBA genotype. Further analyses revealed
that proband's duplicated beta-globin gene cluster (~650 kb) encompassing HBBA
does not include the immediate upstream locus control region (LCR) or 3' DNase I
hypersensitivity (HS) element. The LCR interacts with beta-globin gene cluster
involving long range DNA interactions mediated by various transcription factors
to drive the regulation of globin genes expression. However, a low level of HBBA
transcript was clearly detected by digital PCR. In this patient, the observed
transcription from the duplicated, distally displaced HBBA cluster demonstrates
that the loss of LCR and flanking 3'HS sites do not lead to complete silencing of
HBB transcription.
PMID- 27492749
TI - Innovation in Graduate Education for Health Professionals in Humanitarian
Emergencies.
AB - The objective of this report was to show how the Center for Humanitarian
Emergencies (the Center) at Emory University (Atlanta, Georgia USA) has trained
graduate students to respond to complex humanitarian emergencies (CHEs) through
innovative educational programs, with the goal of increasing the number of
trained humanitarian workers. Natural disasters are on the rise with more than
twice as many occurring from 2000-2009 as there were from 1980-1989. In 2012
alone, 144 million people were affected by a natural disaster or displaced by
conflict worldwide. This has created an immense need for trained humanitarian
workers to respond effectively to such disasters. The Center has developed a
model for educational programming that targets learners along an educational
continuum ranging from the undergraduate level through continuing professional
education. These programs, based in the Rollins School of Public Health (RSPH) of
Emory University, include: a competency-based graduate certificate program (the
Certificate) in humanitarian emergencies; a fellowship program for mid-career
professionals; and funded field practica. The competency-based Certificate
program began in 2010 with a cohort of 14 students. Since then, 101 students have
received the Certificate with 50 more due for completion in 2016 and 2017
combined. The fellowship program for mid-career professionals has hosted four
fellows from conflict-affected or resource-poor countries, who have then gone on
to assume leadership positions with humanitarian organizations. From 2009-2015,
the field practicum program supported 34 students in international summer
practicum experiences related to emergency response or preparedness. Students
have participated in summer field experiences on every continent but Australia.
Together the Certificate, funded field practicum opportunities, and the
fellowship comprise current efforts in providing innovative education and
training for graduate and post-graduate students of public health in humanitarian
response. These modest efforts are just the beginning in terms of addressing the
global shortage of skilled public health professionals that can coordinate
humanitarian response. Evaluating existing programs will allow for refinement of
current programs. Ultimately, these programs may influence the development of new
programs and inform others interested in this area. Evans DP , Anderson M ,
Shahpar C , del Rio C , Curran JW . Innovation in graduate education for health
professionals in humanitarian emergencies. Prehosp Disaster Med. 2016;31(5):532
538.
PMID- 27492750
TI - Subacute pneumonia as a manifestation of acute fibrinous and organizing
pneumonia.
PMID- 27492751
TI - Endoscopic Cyanoacrylate for Persistent Air Leak from A Bronchopleural Fistula in
A Patient with Idiopathic Pulmonary Fibrosis.
PMID- 27492752
TI - Seasonal importance of flowers to Costa Rican capuchins (Cebus capucinus
imitator): Implications for plant and primate.
AB - OBJECTIVES: Our goal is to investigate flower foraging by capuchin monkeys, a
behavior rarely studied in wild primates. We ask what drives seasonal variation
in florivory rates: flower quality and abundance or fluctuations in fruit and
invertebrate abundances. We explore how capuchins affect the reproductive success
of flower food species by quantifying the potential pollination rate. MATERIALS
AND METHODS: We followed capuchin groups from dawn to dusk and recorded all
flower foraging bouts. Flower food nutritional composition was compared to fruit
and invertebrate foods. We recorded overall flower, fruit, and invertebrate
abundances and compared the rate of flower foraging to these. We estimated the
likelihood of pollination from the proportion of flower patch visits to each
plant species that satisfied minimum behavioral requirements. RESULTS: Flower
eating was highly seasonal, and was significantly negatively related to overall
fruit and invertebrate abundance but not flower abundance. Although smaller than
most fruits, flowers were nutritionally comparable to fruit foods by dry mass and
contained higher average concentrations of protein. Capuchins are likely
pollinators for Luehea speciosa; most foraging visits to this species occurred in
a manner that makes outcrossing or geitonogamous pollination likely. DISCUSSION:
Flowers are an important seasonal resource for capuchins. Flowers likely act as
fallback foods during periods of reduced fruit and invertebrate abundance, and
may exert evolutionary pressure disproportionate to their consumption. Capuchin
florivory likely affects the reproductive success of some plants, potentially
shaping forest structure. Our study illustrates the value of assessing the
importance of rare foods in the primate diet.
PMID- 27492753
TI - Spatial clustering of average risks and risk trends in Bayesian disease mapping.
AB - Spatiotemporal disease mapping focuses on estimating the spatial pattern in
disease risk across a set of nonoverlapping areal units over a fixed period of
time. The key aim of such research is to identify areas that have a high average
level of disease risk or where disease risk is increasing over time, thus
allowing public health interventions to be focused on these areas. Such aims are
well suited to the statistical approach of clustering, and while much research
has been done in this area in a purely spatial setting, only a handful of
approaches have focused on spatiotemporal clustering of disease risk. Therefore,
this paper outlines a new modeling approach for clustering spatiotemporal disease
risk data, by clustering areas based on both their mean risk levels and the
behavior of their temporal trends. The efficacy of the methodology is established
by a simulation study, and is illustrated by a study of respiratory disease risk
in Glasgow, Scotland.
PMID- 27492754
TI - Immunopharmacology of fatty acids.
PMID- 27492755
TI - Hemispheric specialization of mood processing is abnormal in patients with
schizophrenia.
PMID- 27492756
TI - Siderophores as molecular tools in medical and environmental applications.
AB - Almost all life forms depend on iron as an essential micronutrient that is needed
for electron transport and metabolic processes. Siderophores are low-molecular
weight iron chelators that safeguard the supply of this important metal to
bacteria, fungi and graminaceous plants. Although animals and the majority of
plants do not utilise siderophores and have alternative means of iron
acquisition, siderophores have found important clinical and agricultural
applications. In this review, we will highlight the different uses of these iron
chelating molecules.
PMID- 27492757
TI - Metaproteomics reveals metabolic transitions between healthy and diseased stony
coral Mussismilia braziliensis.
AB - Infectious diseases such as white plague syndrome (WPS) and black band disease
(BBD) have caused massive coral loss worldwide. We performed a metaproteomic
study on the Abrolhos coral Mussismilia braziliensis to define the types of
proteins expressed in healthy corals compared to WPS- and BBD-affected corals. A
total of 6363 MS/MS spectra were identified as 361 different proteins. Healthy
corals had a set of proteins that may be considered markers of holobiont
homoeostasis, including tubulin, histone, Rab family, ribosomal, peridinin
chlorophyll a-binding protein, F0F1-type ATP synthase, alpha-iG protein,
calmodulin and ADP-ribosylation factor. Cnidaria proteins found in healthy M.
braziliensis were associated with Cnidaria-Symbiodinium endosymbiosis and
included chaperones (hsp70, hsp90 and calreticulin), structural and membrane
modelling proteins (actin) and proteins with functions related to intracellular
vesicular traffic (Rab7 and ADP-ribosylation factor 1) and signal transduction
(14-3-3 protein and calmodulin). WPS resulted in a clear shift in the
predominance of proteins, from those related to aerobic nitrogen-fixing bacteria
(i.e. Rhizobiales, Sphingomonadales and Actinomycetales) in healthy corals to
those produced by facultative/anaerobic sulphate-reducing bacteria (i.e.
Enterobacteriales, Alteromonadales, Clostridiales and Bacteroidetes) in WPS
corals. BBD corals developed a diverse community dominated by cyanobacteria and
sulphur cycle bacteria. Hsp60, hsp90 and adenosylhomocysteinase proteins were
produced mainly by cyanobacteria in BBD corals, which is consistent with elevated
oxidative stress in hydrogen sulphide- and cyanotoxin-rich environments. This
study demonstrates the usefulness of metaproteomics for gaining better
comprehension of coral metabolic status in health and disease, especially in reef
systems such as the Abrolhos that are suffering from the increase in global and
local threatening events.
PMID- 27492758
TI - Minority groups and the artificial pancreas: who is (not) in line?
PMID- 27492759
TI - De-evolution of diagnostic testing for adrenal insufficiency.
PMID- 27492760
TI - Choosing estimands in clinical trials with missing data.
AB - Recent research has fostered new guidance on preventing and treating missing
data. Consensus exists that clear objectives should be defined along with the
causal estimands; trial design and conduct should maximize adherence to the
protocol specified interventions; and a sensible primary analysis should be used
along with plausible sensitivity analyses. Two general categories of estimands
are effects of the drug as actually taken (de facto, effectiveness) and effects
of the drug if taken as directed (de jure, efficacy). Motivated by examples, we
argue that no single estimand is likely to meet the needs of all stakeholders and
that each estimand has strengths and limitations. Therefore, stakeholder input
should be part of an iterative study development process that includes choosing
estimands that are consistent with trial objectives. To this end, an example is
used to illustrate the benefit from assessing multiple estimands in the same
study. A second example illustrates that maximizing adherence reduces sensitivity
to missing data assumptions for de jure estimands but may reduce generalizability
of results for de facto estimands if efforts to maximize adherence in the trial
are not feasible in clinical practice. A third example illustrates that whether
or not data after initiation of rescue medication should be included in the
primary analysis depends on the estimand to be tested and the clinical setting.
We further discuss the sample size and total exposure to placebo implications of
including post-rescue data in the primary analysis. Copyright (c) 2016 John Wiley
& Sons, Ltd.
PMID- 27492762
TI - Comparison of apoptosis pathway following the use of two protocols for
vitrification of immature mouse testicular tissue.
AB - Our objective was to evaluate the apoptosis incidence in immature mouse
testicular tissue after two different protocols of vitrification and short-term
culture. Testes of 7-day-old Naval Medical Research Institute mice were isolated
and distributed into control and vitrification groups. In vitrification 1 group,
testes were vitrified using a combination of ethylene glycol and DMSO in three
steps, and in vitrification 2 group, testes were vitrified using a combination of
ethylene glycol and sucrose in five steps. Then, fresh and vitrified-warmed
testis fragments were cultured for 20 hours. Morphology, cell viability,
apoptosis incidence, and apoptosis gene expression (BAX, BCL2, Caspase 3, Fas,
Fas ligand, p53) were evaluated at 0, 3, and 20 hours of culture by light
microscopy, flow cytometry, and real-time polymerase chain reaction,
respectively. Significant decrease of early apoptosis (annexin V+/PI- cells in
vitrification 1 and 2 groups at 0 hours of culture, 37.34 +/- 0.91 and 30.72 +/-
2.2, and at 20 hours of culture, 1.46 +/- 0.28 and 0.76 +/- 0.11, respectively),
increase of late apoptosis (annexin V+/PI+ cells in vitrification 1 group at 0
hours of culture, 14.46 +/- 0.86, and at 20 hours of culture, 37.18 +/- 2.34),
and BAX/BCL-2 ratio (in vitrification 1 and 2 groups at 0 hours of culture, 7.31
+/- 0.31 and 6.83 +/- 1.38, and at 20 hours of culture, 24.08 +/- 4.32 and 9.35
+/- 1.91, respectively) were observed in vitrification groups during culture
period. Caspase 3 expression was significantly decreased in all groups after 3
hours of culture (in control, vitrification 1, and vitrification 2 groups at 0
hours of culture, 1.00 +/- 0.0, 1.56 +/- 0.09, and 0.79 +/- 0.06, and at 20 hours
of culture, 0.37 +/- 0.0, 0.96 +/- 0.10, and 0.12 +/- 0.03, respectively).
Expression of p53 was significantly lower in vitrification 1 (0.32 +/- 0.02) and
control (0.50 +/- 0.03) groups in 20 hours of culture as compared with
vitrification 2 (0.88 +/- 0.14) group. Fas (in vitrification 1 and 2 groups at 0
hours of culture, 2.29 +/- 0.23 and 1.14 +/- 0.15, and at 20 hours of culture,
12.43 +/- 0.46 and 6.7 +/- 0.48, respectively) and Fas Ligand (in vitrification 1
and 2 groups at 0 hours of culture, 1.2 +/- 0.28 and 5.24 +/- 0.32, and at 20
hours of culture, 21.75 +/- 2.00 and 25.82 +/- 2.15, respectively) expressions
significantly increased in vitrification groups after 20 hours of culture.
Although both vitrification protocols cause cell death via apoptotic and necrotic
pathway, it seems that vitrification 1 protocol induces cell death more via
apoptotic pathway than via necrosis. The apoptosis incidence after vitrification
may have occurred independent of p53.
PMID- 27492761
TI - Impact of polymer-modified gold nanoparticles on brain endothelial cells:
exclusion of endoplasmic reticulum stress as a potential risk factor.
AB - A library of polymer-coated gold nanoparticles (AuNPs) differing in size and
surface modifications was examined for uptake and induction of cellular stress
responses in the endoplasmic reticulum (ER stress) in human brain endothelial
cells (hCMEC/D3). ER stress is known to affect the physiology of endothelial
cells (ECs) and may lead to inflammation or apoptosis. Thus, even if applied at
non-cytotoxic concentrations ER stress caused by nanoparticles should be
prevented to reduce the risk of vascular diseases and negative effects on the
integrity of barriers (e.g. blood-brain barrier). We exposed hCMEC/D3 to twelve
different AuNPs (three sizes: 18, 35, and 65 nm, each with four surface
modifications) for various times and evaluated their effects on cytotoxicity,
proinflammatory mediators, barrier functions and factors involved in ER stress.
We demonstrated a time-dependent uptake of all AuNPs and no cytotoxicity for up
to 72 h of exposure. Exposure to certain AuNPs resulted in a time-dependent
increase in the proinflammatory markers IL-8, MCP-1, sVCAM, sICAM. However, none
of the AuNPs induced an increase in expression of the chaperones and stress
sensor proteins BiP and GRP94, respectively, or the transcription factors ATF4
and ATF6. Furthermore, no upregulation of the UPR stress sensor receptor PERK, no
active splicing product of the transcription factor XBP1 and no upregulation of
the transcription factor CHOP were detectable. In conclusion, the results of the
present study indicate that effects of different-sized gold nanoparticles
modified with various polymers were not related to the induction of ER stress in
brain microvascular endothelial cells or led to apoptosis.
PMID- 27492763
TI - Tracking Effects of Problematic Social Networking on Adolescent Psychopathology:
The Mediating Role of Sleep Disruptions.
AB - Concerns are growing about adolescents' problematic social networking and
possible links to depressed mood and externalizing behavior. Yet there remains
little understanding of underlying processes that may account for these
associations, including the mediating role of sleep disruption. This study tests
this putative mediating process and examines change in problematic social
networking investment and disrupted sleep, in relation to change in depressed
mood and externalizing behavior. A sample of 874 students (41% male; 57.2%
Caucasian; baseline M age = 14.4 years) from 27 high schools were surveyed.
Participants' problematic social networking, sleep disruption, and
psychopathology (depressed mood, externalizing behaviors) were measured annually
over 3 years. Longitudinal mediation was tested using latent trajectories of
problematic social networking use, sleep disruption, and psychopathology. Both
problematic social networking and sleep disruption underwent positive linear
growth over time. Adolescents who increasingly invested in social networking
reported increased depressed mood, with around 53% of this association explained
by the indirect effect of increased sleep disruptions. Further, adolescents who
increasingly invested in social networking also reported increased externalizing
behavior; some of this relation was explained (13%) via increased sleep
disruptions. However an alternative model in which increased externalizing was
associated with increased social networking, mediated by sleep disruptions,
indicated a reciprocal relation of similar magnitude. It is important for
parents, teachers, and psychologists to minimize the negative effects of social
networking on adolescents' psychopathology. Interventions should potentially
target promoting healthy sleep habits through reductions in social networking
investment and rescheduling usage away from bedtime.
PMID- 27492764
TI - A multicenter 12-month experience with a new iliac side-branched device for
revascularization of hypogastric arteries.
AB - OBJECTIVE: The aim of this study was to investigate the 1-year safety and
efficacy of a new iliac side-branched device (IBD) for revascularization of the
hypogastric arteries. METHODS: Patients receiving the E-liac (Jotec GmbH,
Hechingen, Germany) side-branched device at six German vascular centers either as
a stand-alone procedure or in combination with abdominal aortic aneurysm
exclusion were included in a prospectively created data bank. Collected data were
analyzed for baseline characteristics, procedural events, and clinical follow-up;
variables included endoleaks, reinterventions, and internal iliac artery (IIA)
patency. RESULTS: Between January 2012 and January 2015, a total of 70 patients
(69 men [98.6%]) with a median age of 74 years (range, 51-87 years) were
consecutively treated; 66 patients had aneurysmatic disease of the iliac
arteries, 2 patients had a para-anastomotic aneurysm after aortobi-iliac
reconstruction, and another 2 patients had a type Ib endoleak after endovascular
aneurysm repair. A total of 82 IIAs were revascularized, 12 bilaterally.
Technical success was achieved in 100% (82/82) of the revascularized IIAs. All
IBDs were patent at the end of the procedure. No instances of myocardial
infarction, stroke, conversion to open repair, mesenteric or spinal cord
infarction, or buttock necrosis were observed. There was one perioperative death
(1.4%) in a 70-year-old patient with intraoperative gastrointestinal bleeding
leading to multiple organ failure, which resulted in the patient's death on the
fifth postoperative day. Within 30 days, one symptomatic occlusion of a treated
common iliac artery (CIA) was observed. In two other patients, an asymptomatic
kinking of the CIA segment of the IBD was revealed in the predischarge follow-up
duplex ultrasound examination and corrected with relining. Median follow-up was
12 months (range, 6-16 months). One patient was lost during the follow-up period.
Survival at 1 year was 98.5% with all IIAs remaining patent, whereas two CIA and
two external iliac artery limb occlusions occurred. According to life-table
analysis, the freedom from occlusion in a patient was 92% at 1 year, and freedom
from type I endoleak was 87% at 1 year. CONCLUSIONS: This first ever 1-year study
reports the results with the new E-liac device and shows that it can be safely
applied for the treatment of aortoiliac aneurysmatic disease with low
reintervention rates and high patency rates. Long-term data are needed to confirm
the durability of the device.
PMID- 27492765
TI - Electromobility Shift Assay Reveals Evidence in Favor of Allele-Specific Binding
of RUNX1 to the 5' Hypersensitive Site 4-Locus Control Region.
AB - In our previous studies on the Iranian beta-thalassemia (beta-thal) patients, we
identified an association between the severity of the beta-thal phenotype and the
polymorphic palindromic site at the 5' hypersensitive site 4-locus control region
(5'HS4-LCR) of the beta-globin gene cluster. Furthermore, a linkage
disequilibrium was observed between this region and XmnI-HBG2 in the patient
population. Based on this data, it was suggested that the well-recognized
phenotype-ameliorating role assigned to positive XmnI could be associated with
its linked elements in the LCR. To investigate the functional significance of
polymorphisms at the 5'HS4-LCR, we studied its influence on binding of
transcription factors. Web-based predictions of transcription factor binding
revealed a binding site for runt-related transcription factor 1 (RUNX1), when the
allele at the center of the palindrome (TGGGG(A/G)CCCCA) was A but not when it
was G. Furthermore, electromobility shift assay (EMSA) presented evidence in
support of allele-specific binding of RUNX1 to 5'HS4. Considering that RUNX1 is a
well-known regulator of hematopoiesis, these preliminary data suggest the
importance of further studies to confirm this interaction and consequently
investigate its functional and phenotypical relevance. These studies could help
us to understand the molecular mechanism behind the phenotype modifying role of
the 5'HS4-LCR polymorphic palindromic region (rs16912979), which has been
observed in previous studies.
PMID- 27492767
TI - Occurrence of the - -(SEA), - -(THAI) and - -(FIL) alpha-Thalassemia-1 Carriers
from a 7-Year Study at Ramathibodi Hospital, Bangkok, Thailand.
AB - alpha-Thalassemia (alpha-thal) is one of the most common genetic diseases in
Thailand. Homozygosity of alpha-thal-1 (- -/- -) and compound heterozygosity of
alpha-thal-1/alpha-thal-2 (- -/-alpha) leads to Hb Bart's (gamma4) hydrops
fetalis and Hb H (beta4) disease, respectively. In order to better control and
provide prevention of alpha-thal disease, the prevalence of alpha-thal-1 carriers
and the types of genotypes in the Thai population should be known. A 7-year
retrospective study, employing multiplex gap-polymerase chain reaction (gap-PCR)
of 31,632 blood samples from Ramathibodi Hospital, Mahidol University, Bangkok,
revealed an alpha-thal-1 carrier rate of 14.40% with the - -(SEA) (NG_000006.1:
g.26264_45564del19301), - -(THAI) (NG_000006.1: g.10664_44164del33501) and -
(FIL) (NG_000006.1: g.11684_43534del31851) genotypes, constituting frequencies of
14.21, 0.18 and 0.01%, respectively. Although the - -(FIL) genotype is rare in
the Thailand, its detection should be included in future alpha-thal screening
programs.
PMID- 27492766
TI - Identification of a Novel beta-Globin Mutation (HBB: C.189_195delTCATGGC) in a
Chinese Family.
AB - beta-Thalassemia (beta-thal) is one of the most common genetic disorders
worldwide. Molecular characterization of beta-thal is essential for prevention
and understanding the biology of the disease. More and more rare and novel
mutations are being reported. Here, we report a novel 7 bp deletion at codons 63
65 (HBB: c.189_195delTCATGGC) in exon 2 of the beta-globin gene in a family from
Guangxi Province, China. This novel mutation causes a shift in the normal reading
frame of the beta-globin coding sequence and created a stop codon at codon 87 in
exon 2, which leads to a beta(0)-thal phenotype.
PMID- 27492768
TI - The -(alpha)(5.2) Deletion Detected in a Uruguayan Family: First Case Report in
the Americas.
AB - In Uruguay, alpha-thalassemia (alpha-thal) mutations were introduced
predominantly by Mediterranean European immigrant populations and by slave trade
of African populations. A patient with anemia with hypochromia and microcytosis,
refractory to iron treatment and with normal hemoglobin (Hb) electrophoresis was
analyzed for alpha-thal mutations by multiplex gap-polymerase chain reaction (gap
PCR), automated sequencing and multiplex ligation-dependent probe amplification
(MLPA) analyses. Agarose gel electrophoresis of the multiplex gap-PCR showed a
band of unexpected size (approximately 700 bp) in the samples from the proband
and mother. Automated sequencing of the amplified fragment showed the presence of
the -(alpha)(5.2) deletion (NG_000006.1: g.32867_38062del5196) [an alpha-thal-1
deletion of 5196 nucleotides (nts)]. The MLPA analysis of the proband's sample
also showed the presence of the -(alpha)(5.2) deletion in heterozygous state. We
report here the presence of the -(alpha)(5.2) deletion, for the first time in the
Americas, in a Uruguayan family with Italian ancestry, detected with a previously
described multiplex gap-PCR.
PMID- 27492769
TI - Is Vitamin C Supplementation in Patients with beta-Thalassemia Major Beneficial
or Detrimental?
AB - Globally, beta-thalassemia major (beta-TM) is one of the most common hereditary
disorders. Multiple blood transfusions, that are a life-saving therapy in
patients with beta-TM, is a major source of iron overload. Iron overload can lead
to significant morbidity and mortality. Research evidence indicates that
oxidative stress induced by iron overload, is one of the major precipitating
causes of vitamin C deficiency in beta-TM patients. It has previously been shown
that patients with beta-TM have significantly lower levels of vitamin C as
compared to healthy individuals. It is believed that vitamin C can reduce both
ferric (Fe(3+)) and ferrous (Fe(2+)) ions, and also facilitate the accessibility
of iron to chelators through increase of iron release from the
reticuloendothelial system. Despite the potential benefits of vitamin C in
patients with beta-TM, several areas of concern exist that should be addressed by
high quality research designs. Some recommendations have been provided through
this study.
PMID- 27492771
TI - Three-decade long fertilization-induced soil organic carbon sequestration depends
on edaphic characteristics in six typical croplands.
AB - Fertilizations affect soil organic carbon (SOC) content but the relative
influences of the edaphic and climate factors on SOC storage are rarely studied
across wide spatiotemporal scales. This study synthesized long-term datasets of
fertilization experiments in six typical Chinese croplands, and calculated annual
C input from crops and manure amendments, changes in SOC storage (DeltaSOC) and C
sequestration efficiency (i.e. the percentage of soil C change per unit of C
input, hereafter referred as CSE) in 0-20 cm soil over three decades. Three
fertilization treatments include no fertilization (CK), chemical nitrogen,
phosphorus and potassium fertilizers (NPK) and combined chemical fertilizers and
manure (NPKM). Results showed significant fertilization effects on C input and
DeltaSOC (NPKM>NPK>CK), and significantly higher CSE in Qiyang at Hunan than
Zhengzhou at Henan and Heihe at Heilongjiang. The variance partitioning analysis
(VPA) showed more variance of CSE can be explained by edaphic factors (up to
39.7%) than other factors. Furthermore, soil available N content and pH were
identified as the major soil properties explaining CSE variance. This study
demonstrated key controls of soil fertility factors on SOC sequestration and
informs the need to develop strategic soil management plan to promote soil carbon
sequestration under long-term intensive fertilization.
PMID- 27492772
TI - Effects of fiber-glass-reinforced composite restorations on fracture resistance
and failure mode of endodontically treated molars.
AB - OBJECTIVES: The study evaluated the fracture resistance and fracture patterns of
endodontically treated mandibular first molars restored with glass-fiber
reinforced direct composite restorations. METHODS: In total, 60 extracted intact
first molars were treated endodontically; a mesio-occluso-distal (MOD) cavity was
prepared and specimens were then divided into six groups: sound teeth (G1), no
restoration (G2), direct composite restoration (G3), fiber-post-supported direct
composite restoration (G4), direct composite reinforced with horizontal mesio
distal glass-fibers (G5), and buccal-palatal glass-fibers (G6). Specimens were
subjected to 5000 thermocycles and 20,000 cycles of 45 degrees oblique loading
force at 1.3Hz and 50N; they were then loaded until fracture. The maximum
fracture loads were recorded in Newtons (N) and data were analyzed with one-way
ANOVA and post-hoc Tukey tests (p<0.05). Fractured specimens were analyzed with a
scanning electron microscope (SEM). RESULTS: The mean static loads (in Newtons)
were: G1, 831.83; G2, 282.86; G3, 364.18; G4, 502.93; G5, 499.26; and G6, 582.22.
Fracture resistance did not differ among G4, G5, and G6, but was significantly
higher than G3 (p=0.001). All specimens fractured in a catastrophic way. In G6,
glass fibers inducted a partial deflection of the fracture, although they were
not able to stop crack propagation. CONCLUSIONS: For the direct restoration of
endodontically treated molars, reinforcement of composite resins with glass
fibers or fiber posts can enhance fracture resistance. The SEM analysis showed a
low ability of horizontal glass-fibers to deviate the fracture, but this effect
was not sufficient to lead to more favorable fracture patterns above the cement
enamel junction (CEJ). CLINICAL SIGNIFICANCE: The fracture resistance of
endodontically treated molars restored with direct composite restorations seems
to be increased by reinforcement with fibers, even if it is insufficient to
restore sound molar fracture resistance and cannot avoid vertical fractures.
PMID- 27492773
TI - After 12 years, where next for QOF?
PMID- 27492774
TI - Screening for Food Insecurity in Pediatric Clinical Settings: Opportunities and
Barriers.
AB - Food insecurity is a serious health concern among children in the United States
with 15.3 million children living in food insecure households. The American
Academy of Pediatrics recommends that pediatricians screen for food insecurity at
health maintenance visits as identifying children at risk is a crucial step in
the amelioration of food insecurity. Two surveys were administered in a Midwest
pediatric clinic. A cross-sectional survey was electronically distributed to
pediatric providers to assess perceptions of food insecurity among patients,
provider readiness to conduct food security screenings, and barriers to
conducting those screenings. A cross-sectional caregiver survey was administered
to assess demographics, household food security status, participation in
nutrition assistance programs, and barriers to getting enough food to eat.
Descriptive statistics and odds ratios were calculated. Eighty-eight percent of
physicians believe that food insecurity is a challenge for some of their
patients. Only 15 % of providers reported screening for food insecurity, while 80
% were willing to screen. Physicians were most concerned with knowing how to
handle a positive screen. Among caregivers, 57 % screened positive for food
insecurity. Those experiencing food insecurity were more likely to be non-white,
participate in SNAP and to feel discomfort towards the idea of talking to a
doctor or nurse about food needs. Caregivers reporting food insecurity were
significantly less likely to have a personal vehicle. Effective food insecurity
screening requires addressing caregiver and health provider barriers in order to
increase the likelihood of identifying households most at risk.
PMID- 27492775
TI - Jayapura Teenagers Smoking Behavior.
AB - Smoking behavior is a threat for Indonesian teenagers, including in the city of
Jayapura, Papua province. The purpose of this study was to access Jayapura
teenagers smoking behavior and knowledge including parents and other family
members. The study was conducted on 78 respondents (grade 7, aged 11-14 years
old), using cluster random sampling for selecting the public and private junior
high school in Jayapura. The data collected was smoking behavior of respondents,
parents and other family members (using self-reported questionnaire), and
respondents' knowledge about the dangers of smoking (using tests with Cronbach's
alpha 0.701). Data were analyzed descriptively and analytically using Chi-square,
95 % level of significant. The results showed 29.3 % of teenagers, 69.23 % of
parents and 25.6 % of other family members were smokers, their knowledge was low
(an average score of 60.81 out of 100), there was no significant statistical
relationship between knowledge and smoking behavior among respondents (p =
0.079), and there is no significant relationship between teenagers behavior with
the behavior of the parents (p = 0.609) and other family members (p = 0.578), 87
% of teenagers became smokers because there were individuals who smoke at home.
PMID- 27492770
TI - Heterogeneity of B Cell Functions in Stroke-Related Risk, Prevention, Injury, and
Repair.
AB - It is well established that post-stroke inflammation contributes to neurovascular
injury, blood-brain barrier disruption, and poor functional recovery in both
animal and clinical studies. However, recent studies also suggest that several
leukocyte subsets, activated during the post-stroke immune response, can exhibit
both pro-injury and pro-recovery phenotypes. In accordance with these findings, B
lymphocytes, or B cells, play a heterogeneous role in the adaptive immune
response to stroke. This review highlights what is currently understood about the
various roles of B cells, with an emphasis on stroke risk factors, as well as
post-stroke injury and repair. This includes an overview of B cell functions,
such as antibody production, cytokine secretion, and contribution to the immune
response as antigen presenting cells. Next, evidence for B cell-mediated
mechanisms in stroke-related risk factors, including hypertension, diabetes, and
atherosclerosis, is outlined, followed by studies that focus on B cells during
endogenous protection from stroke. Subsequently, animal studies that investigate
the role of B cells in post-stroke injury and repair are summarized, and the
final section describes current B cell-related clinical trials for stroke, as
well as other central nervous system diseases. This review reveals the complex
role of B cells in stroke, with a focus on areas for potential clinical
intervention for a disease that affects millions of people globally each year.
PMID- 27492776
TI - Primary non-refluxive megaureter in children: single-center experience and follow
up of 212 patients.
AB - PURPOSE: Primary non-refluxing megaureter (pMU) is a multifaceted and challenging
congenital pathology of the urinary tract. We report our 23-year experience with
this anomaly in terms of presentation, diagnostic work-up and management.
MATERIALS AND METHODS: We retrospectively reviewed the medical records of 212
children diagnosed with pMU between 1986 and 2009 at our institution. Mean follow
up was 45.17 (0-192) months. RESULTS: Of the total, 168 (79 %) children presented
with upper urinary tract dilation on perinatal ultrasound screening. In 44 (21 %)
patients, the diagnosis was made following diagnostic work-up of a urinary tract
infection (UTI, 18 %) or flank pain (3 %). In total, 203 of 254 pMUs (79.9 %)
were successfully treated conservatively during the 23-year observation period.
Forty-eight children (23 %) underwent ureteric reimplantation. UTIs occurred in
91 of 212 children (43 %). Of these, 41 (45 %) occurred despite antibacterial
infection prophylaxis. Within the past three decades, there has been a marked
shift from surgical toward conservative therapy at our institution. CONCLUSION:
Neonatal renal ultrasound is the method of choice to timely identify children
with pMU and, alongside dynamic renography, to monitor the clinical course.
Nowadays, only a minor subset of children with asymptomatic course requires
surgical correction. Antibacterial prophylaxis has the potential to reduce the
risk of febrile UTIs. Prospective randomized studies are warranted to provide
evidence of the beneficial effect of antibacterial prophylaxis.
PMID- 27492777
TI - Beneath the tip of the iceberg: using electronic referrals to map the
unquantified burden of clinical activity in a urology service.
AB - INTRODUCTION: The aim of this study was to inform health policy by demonstrating
the benefits of an electronic referral (e-referral) system to study inpatient
referrals to urology departments. METHODS: London North West Healthcare NHS Trust
has over 800 beds and several secondary and tertiary care services. In January
2014, we designed an e-referral form to requisition urology input for in-patients
using the Integrated Clinical EnvironmentTM (ICE) platform. We retrospectively
reviewed e-referral records from February to December 2014 for patient
demography, the referring service and disease groups triggering a referral.
RESULTS: There were 1192 referrals. There was a median of 107 e-referrals per
month (IQR 97-123, range 91-132) and 4 per day (IQR 2-6, range 0-12). Weekend e
referrals were 127 (median 1, IQR 0-2, range 0-5) with 1065 e-referrals on
weekdays (median 4, IQR 3-6, range 0-12). A total of 848 (71.1 %) patients were
male, and 344 (28.9 %) were female. Patients' mean age was 63 (SD 21) years.
Almost half (550, 46 %) were acute referrals. Amongst the acute referrals, the
majority (466, 84.7 %) arose from A&E. From the non-acute conditions, 381 (59.3
%) patients were from the medical specialities and 246 (38.3 %) from surgical
disciplines. The three largest disease categories were urolithiasis (287, 24.1
%), haematuria (185, 15.5 %) and for ex-catheterisation (102, 8.6 %). A
qualitative review showed the strengths and weaknesses of the system, enabling
improvements in operational efficiency. CONCLUSION: An e-referral system monitors
activity accurately. Systemic improvement in referral pathways would lead to
better patient care and enable services to factor in the unseen component of
workload and prompt realistic staffing.
PMID- 27492778
TI - Retroperitoneal metastatic germ cell tumor presenting as a psoas abscess: a rare
clinical occurrence and review of the literature.
PMID- 27492779
TI - Seabird acoustic communication at sea: a new perspective using bio-logging
devices.
AB - Most seabirds are very noisy at their breeding colonies, when aggregated in high
densities. Calls are used for individual recognition and also emitted during
agonistic interactions. When at sea, many seabirds aggregate over patchily
distributed resources and may benefit from foraging in groups. Because these
aggregations are so common, it raises the question of whether seabirds use
acoustic communication when foraging at sea? We deployed video-cameras with built
in microphones on 36 Cape gannets (Morus capensis) during the breeding season of
2010-2011 at Bird Island (Algoa Bay, South Africa) to study their foraging
behaviour and vocal activity at sea. Group formation was derived from the camera
footage. During ~42 h, calls were recorded on 72 occasions from 16 birds.
Vocalization exclusively took place in the presence of conspecifics, and mostly
in feeding aggregations (81% of the vocalizations). From the observation of the
behaviours of birds associated with the emission of calls, we suggest that the
calls were emitted to avoid collisions between birds. Our observations show that
at least some seabirds use acoustic communication when foraging at sea. These
findings open up new perspectives for research on seabirds foraging ecology and
their interactions at sea.
PMID- 27492781
TI - Reaching Adolescent Gay, Bisexual, and Queer Men Online: Development and
Refinement of a National Recruitment Strategy.
AB - BACKGROUND: Using social networking websites to recruit research participants is
increasingly documented in the literature, although few studies have leveraged
these sites to reach those younger than 18 years. OBJECTIVE: To discuss the
development and refinement of a recruitment protocol to reach and engage
adolescent gay, bisexual, and other teenaged men who have sex with men (AGBM).
Participants were recruited for development and evaluation activities related to
Guy2Guy, a text messaging-based human immunodeficiency virus infection prevention
program. METHODS: Eligibility criteria included being between 14 to 18 years old;
being a cisgender male; self-identifying as gay, bisexual, and/or queer; being
literate in English, exclusively owning a cell phone, enrolled in an unlimited
text messaging plan, intending to keep their current phone number over the next 6
months, and having used text messaging for at least the past 6 months.
Recruitment experiences and subsequent steps to refine the Internet-based
recruitment strategy are discussed for 4 research activities: online focus
groups, content advisory team, beta test, and randomized controlled trial (RCT).
Recruitment relied primarily on Facebook advertising. To a lesser extent, Google
AdWords and promotion through partner organizations working with AGBM youth were
also utilized. RESULTS: Facebook advertising strategies were regularly adjusted
based on preidentified recruitment targets for race, ethnicity, urban-rural
residence, and sexual experience. The result was a diverse sample of
participants, of whom 30% belonged to a racial minority and 20% were Hispanic.
Facebook advertising was the most cost-effective method, and it was also able to
reach diverse recruitment goals: recruitment for the first focus group cost an
average of US $2.50 per enrolled participant, and it took 9 days to enroll 40
participants; the second focus group cost an average of US $6.96 per enrolled
participant, and it took 11 days to enroll 40 participants. Recruitment for the
first content advisory team cost an average of US $32.52 per enrolled
participant; the second cost US $29.52 per participant. Both recruitment drives
required 10 days to enroll 24 participants. For the beta test, recruitment cost
an average of US $17.19 per enrolled participant, and it took 16 days to complete
enrollment of 20 participants. For the RCT, recruitment cost an average of US
$12.54 per enrolled participant, and it took 148 days to enroll 302 participants.
Google AdWords campaigns did not result in any enrolled participants of whom the
research staff members were aware. CONCLUSIONS: Internet-based strategies can be
a cost-efficient means to recruit and retain hard-to-reach populations from
across the country. With real-time monitoring of participant demographic
characteristics, diverse samples can be achieved. Although Facebook advertising
was particularly successful in this study, alternative social media strategies
can be explored in future research as these media are ever-changing.
PMID- 27492780
TI - miRNA143 Induces K562 Cell Apoptosis Through Downregulating BCR-ABL.
AB - BACKGROUND Leukemia seriously threats human health and life. MicroRNA regulates
cell growth, proliferation, apoptosis, and cell cycle. Whether microRNA could be
treated as a target for leukemia is still unclear and the mechanism by which
microRNA143 regulates K562 cells needs further investigation. MATERIAL AND
METHODS miRNA143 and its scramble miRNA were synthesized and transfected to K562
cells. MTT assay was used to detect K562 cell proliferation. Flow cytometry and a
caspase-3 activity detection kit were used to test K562 cell apoptosis. Western
blot analysis was performed to determine breakpoint cluster region-Abelson (BCR
ABL) expression. BCR-ABL overexpression and siRNA were used to change BCR-ABL
level, and cell apoptosis was detected again after lipofection transfection.
RESULTS miRNA143 transfection inhibited K562 cell growth and induced its
apoptosis. miRNA143 transfection decreased BCR-ABL expression. BCR-ABL
overexpression suppressed miRNA143-induced K562 cell apoptosis, while its
reduction enhanced miRNA143-induced apoptosis. CONCLUSIONS miRNA143 induced K562
cell apoptosis through downregulating BCR-ABL. miRNA143 might be a target for a
new leukemia therapy.
PMID- 27492782
TI - Broadband multiple responses of surface modes in quasicrystalline plasmonic
structure.
AB - We numerically study the multiple excitation of surface modes in 2D photonic
quasicrystal/metal/substrate structure. An improved rigorous coupled wave
analysis method that can handle the quasicrystalline structure is presented. The
quasicrystalline lattice, which refers to Penrose tiling in this paper, is
generated by the cut-and-project method. The normal incidence spectrum presents a
broadband multiple responses property. We find that the phase matching condition
determines the excitation frequency for a given incident angle, while the depth
of the reflection valley depends on the incident polarization. The modes will
split into several sub-modes at oblique incidence, which give rise to the
appearance of more responses on the spectrum.
PMID- 27492784
TI - Reply to Prediction of Non-invasive Mechanical Ventilation Response. Moving from
Art to Science.
PMID- 27492783
TI - PTEN regulates EG5 to control spindle architecture and chromosome congression
during mitosis.
AB - Architectural integrity of the mitotic spindle is required for efficient
chromosome congression and accurate chromosome segregation to ensure mitotic
fidelity. Tumour suppressor PTEN has multiple functions in maintaining genome
stability. Here we report an essential role of PTEN in mitosis through regulation
of the mitotic kinesin motor EG5 for proper spindle architecture and chromosome
congression. PTEN depletion results in chromosome misalignment in metaphase,
often leading to catastrophic mitotic failure. In addition, metaphase cells
lacking PTEN exhibit defects of spindle geometry, manifested prominently by
shorter spindles. PTEN is associated and co-localized with EG5 during mitosis.
PTEN deficiency induces aberrant EG5 phosphorylation and abrogates EG5
recruitment to the mitotic spindle apparatus, leading to spindle disorganization.
These data demonstrate the functional interplay between PTEN and EG5 in
controlling mitotic spindle structure and chromosome behaviour during mitosis. We
propose that PTEN functions to equilibrate mitotic phosphorylation for proper
spindle formation and faithful genomic transmission.
PMID- 27492785
TI - Exciton coupling dynamics in syn- and anti-type beta-beta linked Zn(ii) porphyrin
linear arrays.
AB - The photophysical properties of molecular arrays are strongly dependent on a
variety of structural factors: the constituent chromophores, dihedral angle,
linkage length, linkage position, the center-to-center distance between
chromophores, and the linker itself. Here, we investigated the exciton coupling
dynamics of syn- and anti-type beta-beta directly linked Zn(ii) porphyrin linear
arrays. Focusing on the relationship between the origin of the lowest excited
electronic state and the linkage position, we evaluated the exciton coupling
strength and carried out time-dependent density functional theory (TDDFT)
calculations on model compounds as well as femtosecond transient absorption
anisotropy (fs-TAA) measurements. Based on our experiments and calculations, we
propose that a different origin of the lowest excited state leads to linkage
position-dependent exciton coupling. In short, compared with syn-type porphyrin
arrays, anti-type arrays induce distinct and stronger exciton coupling in the
lowest excited state.
PMID- 27492787
TI - Competing risk bias was common in a prominent medical journal.
PMID- 27492786
TI - Variability between credit units dedicated to dental and clinical sciences in
dental schools across the USA.
AB - PURPOSE: The Commission of Dental Accreditation (CODA) does not set minimum
standards for clock hours of training in Dental and Clinical sciences. The
purpose of this evaluation was to compare United States (US) dental schools for
variability in clock hours. The current paper utilizes the American Dental
Association's survey of clock hours of all US dental schools which is publicly
available data. Clock hours survey from 2010 to 2011 was utilized and the
analysis tool, JMP, was utilized to visualize and report variability.
PERSPECTIVE: The current paper highlights the large variation in clock hours of
training among core clinical subjects in accredited dental schools around the
United States. For example, teaching Physical Evaluations; Oral and
Maxillofacial; and Oral Diagnosis and Treatment Planning were 97.0; 126.6; and
74.4 h. Moreover, upper limit for hours of Operative Dentistry teaching was 1410
h and lower limit was 129 h. Various other fields of education do enforce strict
requirements on educational clock hours. For instance, Massachusetts' General Law
states that both private and public schools must have 900 and 990 h in a school
year for elementary and secondary schools, respectively. However, no such
stipulation exists in the field of Dental Education. CODA's mission is "to serve
the oral health care needs of the public" and CODA must consider if the average
dental patient would consider a dentist who attended the school delivering 1410 h
of Operative Dentistry to be the same standard as a graduate of the school
delivering 129 h.
PMID- 27492788
TI - Point of data saturation was assessed using resampling methods in a survey with
open-ended questions.
AB - OBJECTIVE: To describe methods to determine sample sizes in surveys using open
ended questions and to assess how resampling methods can be used to determine
data saturation in these surveys. STUDY DESIGN AND SETTING: We searched the
literature for surveys with open-ended questions and assessed the methods used to
determine sample size in 100 studies selected at random. Then, we used Monte
Carlo simulations on data from a previous study on the burden of treatment to
assess the probability of identifying new themes as a function of the number of
patients recruited. RESULTS: In the literature, 85% of researchers used a
convenience sample, with a median size of 167 participants (interquartile range
[IQR] = 69-406). In our simulation study, the probability of identifying at least
one new theme for the next included subject was 32%, 24%, and 12% after the
inclusion of 30, 50, and 100 subjects, respectively. The inclusion of 150
participants at random resulted in the identification of 92% themes (IQR = 91
93%) identified in the original study. CONCLUSION: In our study, data saturation
was most certainly reached for samples >150 participants. Our method may be used
to determine when to continue the study to find new themes or stop because of
futility.
PMID- 27492789
TI - The effects of methylphenidate and propranolol on the interplay between induced
anxiety and working memory.
AB - RATIONALE: Research documents a reciprocal impact of anxiety on working memory
(WM), although its strength and direction depend on factors like task difficulty.
A better understanding of these factors may generate insights into cognitive
mechanisms of action involved in anxiety, culminating into treatment
implications. By blocking the physiological effects of anxiety, propranolol might
also block anxiety interference on WM. Conversely, by improving task-directed
attention, methylphenidate might reduce anxiety, or, alternatively, by improving
cognitive efficiency and free up processing resources to compute anxiety.
OBJECTIVES: To investigate the interplay between induced anxiety and WM, we
pharmacologically manipulated either anxiety or cognition, using single doses of
40 mg propranolol (PRO), 20 mg methylphenidate (MPH), or placebo (PLA). In this
double-blind parallel-group design study, 60 healthy volunteers (20/drug group)
performed a verbal WM task under three loads, 1-, 2- and 3-back, and in two
conditions, threat of shock and safety. Startle electromyography (EMG) was used
to measure anxiety. RESULTS: Findings were twofold: (1) MPH blocked anxiety
interference only on the 3-back WM performance, while PRO or PLA had no effects
on anxiety-WM interference, and (2) drugs had no effects on anxiety, but, after
controlling for baseline anxiety, MPH enhanced anxiety-potentiated startle during
the 3-back task. CONCLUSIONS: These findings support that MPH-related improvement
of cognitive efficiency permits anxiety to be processed and expressed. In
conclusion, MPH may be a useful tool to investigate the mechanisms of interaction
between anxiety and WM, particularly those under catecholaminergic control.
PMID- 27492791
TI - Lewis Acids as Activators in CBS-Catalysed Diels-Alder Reactions: Distortion
Induced Lewis Acidity Enhancement of SnCl4.
AB - The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi
and Shibata) was investigated in this study. While (2) H NMR spectroscopic
measurements served as gauge for the activation capability of the Lewis acids, in
situ FT-IR spectroscopy was employed to assess the catalytic activity of the
Lewis acid oxazaborolidine complexes. A correlation was found between the
Deltadelta((2) H) values and rate constants kDA , which indicates a direct
translation of Lewis acidity into reactivity of the Lewis acid-CBS complexes.
Unexpectedly, a significant deviation was found for SnCl4 as Lewis acid. The
SnCl4 -CBS adduct was much more reactive than the Deltadelta((2) H) values
predicted and gave similar reaction rates to those observed for the prominent
AlBr3 -CBS adduct. To rationalize these results, quantum mechanical calculations
were performed. The frontier molecular orbital approach was applied and a good
correlation between the LUMO energies of the Lewis acid-CBS-naphthoquinone
adducts and kDA could be found. For the SnCl4 -CBS-naphthoquinone adduct an
unusual distortion was observed leading to an enhanced Lewis acidity. Energy
decomposition analysis with natural orbitals for chemical valence (EDA-NOCV)
calculations revealed the relevant interactions and activation mode of SnCl4 as
Lewis acid in Diels-Alder reactions.
PMID- 27492790
TI - Reduction of methicillin-resistant Staphylococcus aureus infection in long-term
care is possible while maintaining patient socialization: A prospective
randomized clinical trial.
AB - BACKGROUND: Antibiotic resistance is a challenge in long-term care facilities
(LTCFs). The objective of this study was to demonstrate that a novel, minimally
invasive program not interfering with activities of daily living or socialization
could lower methicillin-resistant Staphylococcus aureus (MRSA) disease. METHODS:
This was a prospective, cluster-randomized, nonblinded trial initiated at 3
LTCFs. During year 1, units were stratified by type of care and randomized to
intervention or control. In year 2, all units were converted to intervention
consisting of universal decolonization using intranasal mupirocin and a
chlorhexidine bath performed twice (2 decolonization-bathing cycles 1 month
apart) at the start of the intervention period. Subsequently, after initial
decolonization, all admissions were screened on site using real-time polymerase
chain reaction, and those MRSA positive were decolonized, but not isolated. Units
received annual instruction on hand hygiene. Enhanced bleach wipe cleaning of
flat surfaces was done every 4 months. RESULTS: There were 16,773 tests
performed. The MRSA infection rate decreased 65% between baseline (44 infections
during 365,809 patient days) and year 2 (12 infections during 287,847 patient
days; P <.001); a significant reduction was observed at each of the LTCFs (P
<.03). CONCLUSIONS: On-site MRSA surveillance with targeted decolonization
resulted in a significant decrease in clinical MRSA infection among LTCF
residents.
PMID- 27492792
TI - Achieving Molecular Remission before Allogeneic Stem Cell Transplantation in
Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic
Leukemia: Impact on Relapse and Long-Term Outcome.
AB - Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1)
remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute
lymphoblastic leukemia (ALL). The prognostic value of measurable levels of
minimal residual disease (MRD) at time of conditioning is a matter of debate. We
analyzed the predictive relevance of MRD levels before transplantation on the
clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2
consecutive prospective clinical trials. MRD evaluation before transplantation
was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A
complete or major molecular response at time of conditioning was achieved in 24
patients (37%), whereas 41 (63%) remained carriers of any other positive MRD
level in the bone marrow. MRD negativity at time of conditioning was associated
with a significant benefit in terms of risk of relapse at 5 years, with a relapse
incidence of 8% compared with 39% for patients with MRD positivity (P = .007).
However, thanks to the post-transplantation use of tyrosine kinase inhibitors
(TKIs), disease-free survival was 58% versus 41% (P = .17) and overall survival
was 58% versus 49% (P = .55) in MRD-negative compared with MRD-positive patients,
respectively. The cumulative incidence of nonrelapse mortality was similar in the
2 groups. Achieving a complete molecular remission before transplantation reduces
the risk of leukemia relapse even though TKIs may still rescue some patients
relapsing after transplantation.
PMID- 27492793
TI - Novel Scoring Criteria for the Evaluation of Ocular Graft-versus-Host Disease in
a Preclinical Allogeneic Hematopoietic Stem Cell Transplantation Animal Model.
AB - Ocular complications occur after transplantation in 60% to 90% of chronic graft
versus-host disease (GVHD) patients and significantly impair vision-related
quality of life. Ocular surface inflammation and dry eye disease are the most
common manifestations of ocular GVHD. Ocular GVHD can be viewed as an excellent
preclinical model that can be studied to understand the immune pathogenesis of
this common and debilitating disease. A limitation of this is that only a few
experimental models mimic the ocular complications after hematopoietic stem cell
transplantation (HSCT) and have focused on the acute GVHD process. To address
this issue, we used a preclinical animal model developed by our group where
ocular involvement was preceded by systemic GVHD to gain insight regarding the
contributing immune mechanisms. Employing this "matched unrelated donor" model
enabled the development of clinical scoring criteria, which readily identified
different degrees of ocular pathology at both the ocular surface and adnexa,
dependent on the level of conditioning before HSCT. As far as we are aware, we
report for the first time that these clinical and immune responses occur not only
on the ocular surface, but they also heavily involve the lid margin region. In
total, the present study reports a preclinical scoring model that can be applied
to animal models as investigators look to further explore GVHD's immunologic
effects at the level of the ocular surface and eyelid adnexa compartments. We
speculate that future studies will use this clinical scoring index in combination
with what is recognized histologically and correlated with serum biomarkers
identified in chronic/ocular GVHD.
PMID- 27492795
TI - Comment on: Is high-intensity interval training more effective on improving
cardiometabolic risk and aerobic capacity than other forms of exercise in
overweight and obese youth? A meta-analysis.
PMID- 27492794
TI - Haploidentical and Matched Sibling Donor Hematopoietic Cell Transplantation for
Patients with HLA-Homozygous Haplotypes.
AB - More than 1% of the Japanese population has HLA-homozygous haplotypes. For
patients with such haplotypes, HLA-haploidentical family members who have no HLA
mismatch in the graft-versus-host direction are readily available donor
candidates for hematopoietic cell transplantation (HCT). In this study, the
outcomes of patients with homozygous HLA-A, -B, and -DRB1 antigens who received
HCT without T cell depletion from a haploidentical related donor with mismatches
in the host-versus-graft direction only (hetero-to-homo, n = 78) or from an HLA
matched sibling donor (MSD) (MSD-homo, n = 153) were compared with those in
patients with heterozygous haplotypes who received HCT from an MSD (MSD-hetero, n
= 7242). Transplant outcomes in the hetero-to-homo group were similar to those in
the MSD-hetero group regarding neutrophil engraftment, grades III to IV acute
graft-versus-host disease (aGVHD), nonrelapse mortality (NRM), relapse, and
overall survival. On the other hand, the incidences of severe aGVHD and NRM in
the MSD-homo group were significantly lower than those in the MSD-hetero group
(grades III to IV aGVHD: aHR .50, P = .034; NRM: aHR .48, P = .004). In
conclusion, patients with HLA-homozygous haplotypes achieved lower GVHD and NRM
rates for MSD transplantation than those with HLA-heterozygous haplotypes. When
an MSD or an appropriate alternative donor is not available for patients with HLA
homozygous haplotypes who need immediate transplantation, transplantation from a
haploidentical donor without T cell depletion is a viable option, given the
comparable transplant outcomes for hetero-to-homo HCT and MSD-hetero HCT.
PMID- 27492796
TI - Frequency and risks associated with Clostridium difficile-associated diarrhea
after pediatric solid organ transplantation: a single-center retrospective
review.
AB - BACKGROUND: Morbidity and mortality related to Clostridium difficile infection
(CDI) has increased, but epidemiology and risk factors within pediatric solid
organ transplant (SOT) recipients are uncertain. METHODS: A retrospective cohort
study of SOT recipients age <=18 years at transplantation from 2010 to 2013 was
performed. Patients with CDI were compared with matched CDI-negative controls
with diarrhea. RESULTS: Of 202 patients, the majority were male (58%) and
Caucasian (77%). Kidney (42%) was the most common organ transplanted, followed by
liver (38%), heart (17%), and multivisceral/intestine (3%). Age ranged from 3
weeks to 18 years (median 4.7 years, mean 6.6; interquartile range [IQR] 1.5
11.2). In 104 SOT recipients, at least 1 unformed stool was tested; 25 patients
were positive for CDI. Most testing occurred by 60 days post transplant (mean
164, median 57, IQR 14-227). First negative tests occurred concurrently (mean
153, median 54, IQR 13-214) to the 25 patients with CDI (mean 199, median 65, IQR
32-238). In univariable analyses, age, gender, ethnicity, obesity, and
calcineurin inhibitor choice were not associated with CDI. Liver recipients were
more likely to have CDI (18.4% liver, 4.7% kidney, 8.8% heart, P < 0.01). Twenty
CDI patients were matched to 35 controls. In multivariable analyses, neither
recent hospitalization nor antibiotic duration or intensity was associated with
CDI. Acid-blockade appeared protective (risk ratio 0.13, 95% confidence interval
0.02-0.78). CONCLUSIONS: CDI occurs in 12% of pediatric SOT recipients, but 24%
of those tested with diarrhea were positive. In patients with diarrhea, prior
hospitalization and antibiotic duration or intensity were not associated with
CDI.
PMID- 27492797
TI - Help-seeking behaviors for serious psychological distress among individuals with
diabetes mellitus: The California Health Interview Survey, 2011-2012.
AB - AIM: To investigate patterns of and factors associated with help-seeking
behaviors among individuals with diabetes mellitus (DM) and/or serious
psychological distress (SPD). METHODS: The analysis was conducted with the
California Health Interview Survey (CHIS) 2011-2012 of 40,803 adults. Logistic
regression was used to examine the associations between the multiple
facilitating/preventing factors and outcome, guided by the Andersen's Health Care
Utilization Model. RESULTS: The prevalence of DM and SPD were 10.9% and 3.4%,
respectively, among participants in the survey. The participants with DM were
more likely to experience SPD than those without DM (OR 1.46, 95% CI=1.11-1.91,
p=0.006). Participants with combined DM and SPD, the most underserved, were less
likely to perceive the need for mental health services and less likely to seek
help, compared to those with only SPD. Need factors (SPD status and perceived
need) were significantly associated with help-seeking behaviors for mental
health, along with predisposing factors (age, gender, obesity, race, and
employment), and enabling factors (insurance, English proficiency). CONCLUSIONS:
Perceptions about need for seeking help seem to play an important role in
receiving mental health services in addition to other predisposing or enabling
factors. Identification of these factors may improve clinical outcomes related to
DM and SPD.
PMID- 27492798
TI - Bishop scoring: Perceived benefits of using in labour induction by Turkish
midwives.
AB - It is not always possible to achieve a successful induction. Bishop scoring
system is an efficient method used in determining whether the induction will be
effective or not. The aim of this study was to train midwives on the benefits and
use of the Bishop scoring system and to minimize the unnecessary use of
induction. This study was conducted as pretest-posttest quasi-experimental
design. This study was conducted in a maternity hospital in Erzurum between 01
February and 31 July 2012. In the study, the midwives received training on the
use of the Bishop scoring system, and changes in their knowledge levels and
application during practice of induction were then evaluated. While only 20% of
midwives were using the Bishop score before the training, 56.7% started to use
this tool after the training. Comparing the examinations performed on pregnant
women by the midwives in the pre-induction period before and after the training,
the mean of the Bishop score changed from 7.26 to 9.68 after the training. It was
determined that the training could increase the knowledge levels of midwives
regarding the Bishop scoring system and their attention paid to the Bishop
scoring system in the practice of induction.
PMID- 27492799
TI - Microarray expression in peri-implant tissue next to different titanium implant
surfaces predicts clinical outcomes: a split-mouth study.
AB - OBJECTIVES: This split-mouth study evaluated miRNA expression of tissues around
implants with different surface treatments. MATERIAL AND METHODS: Each patient of
the sample (five men and five women) received two implants (one control and one
test) into an edentulous quadrant to support fixed partial dentures. The control
implants (Osseotite) had a dual acid-etched (DAE) surface in the apical portion
and a machined coronal part, test implants (Full Osseotite, FOSS) were completely
DAE. Machined healing abutments were placed on control implants and DAE abutments
on test ones. All implants were assigned codes for blinding. Standardized
periapical radiographs were taken at baseline, 2 and 6 months, and 1 year after
surgery. Plaque index (PI), bleeding on probing (BOP), and probing depth (PD)
were recorded at 3 and 6 weeks, and 2, 3, 6, and 12 months post-implant
placement. After 3 months, a mini-invasive sample of soft tissue was collected
from seven patients (four women and three men) for miRNA microarray analysis.
RESULTS: Control implants showed greater bone resorption (BR) and lower PI: this
was not statistically significant. No statistically significant differences in
BOP and PD appeared. miRNA modulated by implant surfaces as well as by other
clinical conditions has been identified. miRNA microarray analysis revealed that:
(i) implant sites with low PI and absence of BOP had a miRNA expression profile
similar to those with plaque and absence of BOP; sites with high PI and high BOP
had a different profile. (ii) Implant sites with BOP presented similar profiles
independently from implant surface. (iii) Implant sites with high PI and normal
BR differed from others for miRNA expression profile. (iv) Implant sites with
normal BR despite high BOP differed from others. This profile resembled that of
FOSS implants. (v) Implant surface affected BR; groups having similar BR
clusterized differently according to the implant type. CONCLUSIONS: DAE surfaces
induced lower BR and more plaque accumulation: This did not affect the health of
soft tissues. miRNA analysis indicated that soft tissue inflammation is more
related to gene expression profile than to plaque or to implant surface. Specific
miRNA profile can protect implant sites from bleeding and BR irrespective of
plaque accumulation.
PMID- 27492800
TI - Endogenous Factors in the Recovery of Reproductive Function After Testicular
Injury and Cancer.
AB - The testes are one of the most delicate organs in the male body and highly
susceptible to the exogenous influences capable of inducing cell damage. Cancer
therapies are well known to negatively affect the male reproductive tract with a
severe impairment of spermatogenesis and infertility. The present work aimed to
systematically review the available information about the different endogenous
factors (hormonal and nonhormonal) that may have protective or advantageous
properties on the recovery of male reproductive function after gonadal injury.
Furthermore, the perspective that these endogenous molecules could act as
cryoprotectants to improve the quality of cryopreserved semen samples was also
discussed. The knowledge reviewed herein allowed to identify promising factors
able to mitigate the male fertility problems arising either from oncological
treatments or other gonadal damage, and opened new possibilities to ameliorate
the recovery of spermatogenesis or to preserve fertility.
PMID- 27492801
TI - Resistin-Like Molecule-alpha Causes Lung Injury in Rats with Acute Pancreatitis
by Activating the PI-3K/Akt-NF-kappaB Pathway and Promoting Inflammatory Cytokine
Release.
AB - BACKGROUND: Resistin-like molecule-alpha (RELMalpha) has diverse regulatory
functions in inflammation, but its role in severe acute pancreatitis (SAP) and
acute pancreatitis associated lung injury (APALI) remains unclear. METHODS: SAP
was induced in rats. RELMalpha protein expression was detected in lung tissue of
rats to determine the relationship between APALI and RELMalpha. To investigate
the effect of RELMalpha overexpression or knockdown on APALI, rats were given an
intravenous injection of adenovirus vector before SAP induction. Lung and
pancreatic samples were harvested 16 h after induction. After detection of
RELMalpha protein levels, the severity of pancreatic and pulmonary injury was
scored histologically, and serum and tissue levels of inflammatory mediators were
measured. TUNEL assay and immunofluorescence were used to estimate pulmonary
apoptosis and endothelial barrier integrity in lung tissue of SAP rats with
RELMalpha knockdown. RESULTS: RELMalpha expression was significantly up-regulated
in APALI and was related to the lung injury index. RELMalpha overexpression
aggravated the release of inflammatory cytokines including interleukin (IL)
1beta, IL-6, IL-8, tumor necrosis factor-alpha, and serum C-reaction protein; the
expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen
activated protein kinase, p-extracellular regulated kinase, and intracellular
adhesion molecule-1; and lung injury. RELMalpha knockdown had opposite effects.
In addition, RELMalpha knockdown improved expression of proliferative cellular
nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP
rats. CONCLUSION: RELMalpha is associated with lung injury severity in SAP.
RELMalpha augments inflammatory activity by increasing inflammatory cytokine
release.
PMID- 27492802
TI - Correction to "Thermodynamic Resistance to Matter Flow at The Interface of a
Porous Membrane".
PMID- 27492803
TI - High-flow-mediated constriction in adults is not influenced by biomarkers of
cardiovascular and metabolic risk.
AB - PURPOSE: During reactive hyperemia, the brachial artery in some individuals
constricts prior to dilation. Our aim was to describe the frequency of high-flow
mediated constriction (H-FMC) in adults, and its relationship to body composition
and biomarkers of cardiovascular and metabolic risk. METHODS: Two hundred forty
six adults (124 male, 122 female; 36 +/- 7 years old) were assessed for H-FMC via
sonographic imaging of the brachial artery. Blood pressure, glucose, insulin,
lipids, and body composition assessed via dual energy X-ray absorptiometry were
collected. H-FMC was characterized as a 10-second average of maximal
postocclusion constriction. Independent t test was used to compare H-FMC versus
non-H-FMC individuals. RESULTS: H-FMC was observed in approximately 69% of adult
participants (54 obese, 57 overweight, and 59 normal weight). Total body mass
(82.3 +/- 17.5 versus 76.3 +/- 16.3 kg, p = 0.012), fat mass (27.7 +/- 11.5
versus 23.8 +/- 10.5 kg, p = 0.012), body mass index (27.7 +/- 4.9 versus 26.1 +/
5.0 kg/m2 , p = 0.018), and low-density lipoprotein cholesterol/high-density
lipoprotein cholesterol ratio (2.41 +/- 1.03 versus 2.09 +/- 0.72, p = 0.007)
were higher in H-FMC than in non-H-FMC individuals. Flow-mediated dilatation
(FMD) (6.12 +/- 3.48 versus 8.09 +/- 3.02%, p < 0.001) was lower in H-FMC
subjects. However, there was no difference in brachial artery dilation between
groups (7.57 +/- 3.69 versus 8.09 +/- 3.02%, p = 0.250) when H-FMC was added to
FMD. CONCLUSIONS: Increased body mass, fat mass, and body mass index were
associated with a greater H-FMC. When H-FMC was present, the FMD response to
reactive hyperemia was significantly lower. Because H-FMC has been observed to
negatively affect FMD response to reactive hyperemia, we suggest that H-FMC
should be noted when analyzing and interpreting FMD data. H-FMC may be an
ancillary measure of endothelial health. (c) 2016 Wiley Periodicals, Inc. J Clin
Ultrasound 45:35-42, 2017.
PMID- 27492804
TI - [Fungal biofilms: Confusion between tolerance and resistance drugs].
PMID- 27492805
TI - Molecular Chaperones in the Pathogenesis of Amyotrophic Lateral Sclerosis: The
Role of HSPB1.
AB - Genetic discoveries in amyotrophic lateral sclerosis (ALS) have a significant
impact on deciphering molecular mechanisms of motor neuron degeneration but,
despite recent advances, the etiology of most sporadic cases remains elusive.
Several cellular mechanisms contribute to the motor neuron degeneration in ALS,
including RNA metabolism, cellular interactions between neurons and nonneuronal
cells, and seeding of misfolded protein with prion-like propagation. In this
scenario, the importance of protein turnover and degradation in motor neuron
homeostasis gained increased recognition. In this study, we evaluated the role of
the candidate gene HSPB1, a molecular chaperone involved in several proteome
maintenance functions. In a cohort of 247 unrelated Italian ALS patients, we
identified two variants (c.570G>C, p.Gln190His and c.610dupG, p.Ala204Glyfs* 6).
Functional characterization of the p.Ala204Glyfs* 6 demonstrated that the mutant
protein alters HSPB1 dynamic equilibrium, sequestering the wild-type protein in a
stable dimer and resulting in a loss of chaperone-like activity. Our results
underline the relevance of identifying rare but pathogenic variations in sporadic
neurodegenerative diseases, suggesting a possible correlation between specific
pathomechanisms linked to HSPB1 mutations and the associated neurological
phenotype. Our study provides additional lines of evidence to support the
involvement of HSPB1 in the pathogenesis of sporadic ALS.
PMID- 27492806
TI - Incidental Dose to Pelvic Nodal Regions in Prostate-Only Radiotherapy.
AB - OBJECTIVES: Pelvic lymph nodal regions receive an incidental dose from conformal
treatment of the prostate. This study was conducted to investigate the doses
received by the different pelvic nodal regions with varying techniques used for
prostate radiotherapy. METHODS AND MATERIALS: Twenty patients of high-risk node
negative prostate cancer treated with intensity-modulated radiotherapy to the
prostate alone were studied. Replanning was done for intensity-modulated
radiotherapy, 3-dimensional conformal treatment, and 2-dimensional conventional
radiotherapy with additional delineation of the pelvic nodal regions, namely,
common iliac (upper and lower), presacral, internal iliac, obturator, and
external iliac. Dose-volume parameters such as Dmean, D100%, D66%, D33%, V40, and
V50 to each of the nodal regions were estimated for all patients. RESULTS: The
obturator nodes received the highest dose among all nodal regions. The mean dose
received by obturator nodal region was 44, 29, and 22 Gy from 2-dimensional
conventional radiotherapy, 3-dimensional conformal treatment, and intensity
modulated radiotherapy, respectively. The mean dose was significantly higher when
compared between 2-dimensional conventional radiotherapy and 3-dimensional
conformal treatment ( P < .001), 2-dimensional conventional radiotherapy and
intensity-modulated radiotherapy ( P < .001), and 3-dimensional conformal
treatment and intensity-modulated radiotherapy ( P < .001). The D33% of the
obturator region was 64, 39, and 37 Gy from 2-dimensional conventional
radiotherapy, 3-dimensional conformal treatment, and intensity-modulated
radiotherapy, respectively. The dose received by all other pelvic nodal regions
was low and not clinically relevant. CONCLUSION: The incidental dose received by
obturator regions is significant especially with 2-dimensional conventional
radiotherapy and 3-dimensional conformal treatment techniques as used in the
trials studying elective pelvic nodal irradiation. However, with intensity
modulated radiotherapy, this dose is lower, making elective pelvic irradiation
more relevant. Advances in Knowledge: This study highlights that incidental dose
received by obturator regions is significant especially with 2-dimensional
conventional radiotherapy and 3-dimensional conformal treatment techniques.
PMID- 27492807
TI - Development and Verification of a Mobile Shelter Assessment System "Rapid
Assessment System of Evacuation Center Condition Featuring Gonryo and Miyagi
(RASECC-GM)" for Major Disasters.
AB - Introduction There were 5,385 deceased and 710 missing in the Ishinomaki medical
zone following the Great East Japan Earthquake that occurred in Japan on March
11, 2011. The Ishinomaki Zone Joint Relief Team (IZJRT) was formed to unify the
relief teams of all organizations joining in support of the Ishinomaki area. The
IZJRT expanded relief activity as they continued to manually collect and analyze
assessments of essential information for maintaining health in all 328 shelters
using a paper-type survey. However, the IZJRT spent an enormous amount of time
and effort entering and analyzing these data because the work was vastly complex.
Therefore, an assessment system must be developed that can tabulate shelter
assessment data correctly and efficiently. The objective of this report was to
describe the development and verification of a system to rapidly assess
evacuation centers in preparation for the next major disaster. Report Based on
experiences with the complex work during the disaster, software called the "Rapid
Assessment System of Evacuation Center Condition featuring Gonryo and Miyagi"
(RASECC-GM) was developed to enter, tabulate, and manage the shelter assessment
data. Further, a verification test was conducted during a large-scale Self
Defense Force (SDF) training exercise to confirm its feasibility, usability, and
accuracy. The RASECC-GM comprises three screens: (1) the "Data Entry screen,"
allowing for quick entry on tablet devices of 19 assessment items, including
shelter administrator, living and sanitary conditions, and a tally of the injured
and sick; (2) the "Relief Team/Shelter Management screen," for registering
information on relief teams and shelters; and (3) the "Data Tabulation screen,"
which allows tabulation of the data entered for each shelter, as well as viewing
and sorting from a disaster headquarters' computer. During the verification test,
data of mock shelters entered online were tabulated quickly and accurately on a
mock disaster headquarters' computer. Likewise, data entered offline also were
tabulated quickly on the mock disaster headquarters' computer when the tablet
device was moved into an online environment. CONCLUSIONS: The RASECC-GM, a system
for rapidly assessing the condition of evacuation centers, was developed. Tests
verify that users of the system would be able to easily, quickly, and accurately
assess vast quantities of data from multiple shelters in a major disaster and
immediately manage the inputted data at the disaster headquarters. Ishii T ,
Nakayama M , Abe M , Takayama S , Kamei T , Abe Y , Yamadera J , Amito K , Morino
K . Development and verification of a mobile shelter assessment system "Rapid
Assessment System of Evacuation Center Condition featuring Gonryo and Miyagi
(RASECC-GM)" for major disasters. Prehosp Disaster Med. 2016;31(5):539-546.
PMID- 27492808
TI - A Novel Adhesion Index for Verifying the Extent of Adhesion for the Extensor
Digitorum Communis in Patients with Metacarpal Fractures.
AB - This study aims to determine if the relative displacement between the extensor
digitorum communis (EDC) tendon and its surrounding tissues can be used as an
adhesion index (AI) for assessing adhesion in metacarpal fractures by comparing
two clinical measures, namely single-digit-force and extensor lag (i.e., the
difference between passive extension and full active extension). The Fisher
Tippett block-matching method and a Kalman-filter algorithm were used to
determine the relative displacements in 39 healthy subjects and 8 patients with
metacarpal fractures. A goniometer was used to measure the extensor lag, and a
force sensor was used to measure the single-digit-force. Measurements were
obtained twice for each patient to evaluate the performance of the AI in
assessing the progress of rehabilitation. The Pearson correlation coefficient was
calculated to quantify the various correlations between the AI, extensor lag, and
single-digit-force. The results showed strong correlations between the AI and the
extensor lag, the AI and the single-digit-force, and the extensor lag and the
single-digit-force (r = 0.718, -0.849, and -0.741; P = 0.002, P < 0.001, and P =
0.001, respectively). The AI in the patients gradually decreased after continuous
rehabilitation, but remained higher than that of healthy participants.
PMID- 27492809
TI - Cluster Analysis of Campylobacter jejuni Genotypes Isolated from Small and Medium
Sized Mammalian Wildlife and Bovine Livestock from Ontario Farms.
AB - Using data collected from a cross-sectional study of 25 farms (eight beef, eight
swine and nine dairy) in 2010, we assessed clustering of molecular subtypes of C.
jejuni based on a Campylobacter-specific 40 gene comparative genomic
fingerprinting assay (CGF40) subtypes, using unweighted pair-group method with
arithmetic mean (UPGMA) analysis, and multiple correspondence analysis. Exact
logistic regression was used to determine which genes differentiate wildlife and
livestock subtypes in our study population. A total of 33 bovine livestock (17
beef and 16 dairy), 26 wildlife (20 raccoon (Procyon lotor), five skunk (Mephitis
mephitis) and one mouse (Peromyscus spp.) C. jejuni isolates were subtyped using
CGF40. Dendrogram analysis, based on UPGMA, showed distinct branches separating
bovine livestock and mammalian wildlife isolates. Furthermore, two-dimensional
multiple correspondence analysis was highly concordant with dendrogram analysis
showing clear differentiation between livestock and wildlife CGF40 subtypes.
Based on multilevel logistic regression models with a random intercept for farm
of origin, we found that isolates in general, and raccoons more specifically,
were significantly more likely to be part of the wildlife branch. Exact logistic
regression conducted gene by gene revealed 15 genes that were predictive of
whether an isolate was of wildlife or bovine livestock isolate origin. Both
multiple correspondence analysis and exact logistic regression revealed that in
most cases, the presence of a particular gene (13 of 15) was associated with an
isolate being of livestock rather than wildlife origin. In conclusion, the
evidence gained from dendrogram analysis, multiple correspondence analysis and
exact logistic regression indicates that mammalian wildlife carry CGF40 subtypes
of C. jejuni distinct from those carried by bovine livestock. Future studies
focused on source attribution of C. jejuni in human infections will help
determine whether wildlife transmit Campylobacter jejuni directly to humans.
PMID- 27492810
TI - Nervous system development in the fairy shrimp Branchinella sp. (Crustacea:
Branchiopoda: Anostraca): Insights into the development and evolution of the
branchiopod brain and its sensory organs.
AB - Using immunohistochemical labeling against acetylated a-tubulin and serotonin in
combination with confocal laser scanning microscopy and 3D-reconstruction, we
investigated the temporary freshwater pond inhabitant Branchinella sp.
(Crustacea: Branchiopoda: Anostraca) for the first time to provide detailed data
on the development of the anostracan nervous system. Protocerebral sense organs
such as the nauplius eye and frontal filament organs are present as early as the
hatching stage L0. In the postnaupliar region, two terminal pioneer neurons grow
from posterior to anterior to connect the mandibular neuromeres. The first
protocerebral neuropil to emerge is not part of the central complex but
represents the median neuropil, and begins to develop from L0+ onwards. In stage
L3, the first evidence of developing compound eyes is visible. This is followed
by the formation of the visual neuropils and the neuropils of the central complex
in the protocerebrum. From the deutocerebral lobes, the projecting neuron tract
proceeds to both sides of the lateral protocerebrum, forming a chiasma just
behind the central body. In the postnaupliar region, the peripheral nervous
system, commissures and connectives develop along an anterior-posterior gradient
after the fasciculation of the terminal pioneer neurons with the mandibular
neuromere. The peripheral nervous system in the thoracic segments consists of two
longitudinal neurite bundles on each side which connect the intersegmental
nerves, together with the ventral nervous system forming an orthogon-like
network. Here, we discuss, among other things, the evidence of a fourth nauplius
eye nerve and decussating projecting neuron tract found in Branchinella sp., and
provide arguments to support our view that the crustacean frontal filament
(organ) and onychophoran primary antenna are homologous. J. Morphol. 277:1423
1446, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27492811
TI - Elevated levels of circulating immunoglobulin E autoantibodies against BP180 and
BP230 in an intractable case of bullous pemphigoid.
PMID- 27492812
TI - Immunomodulation in cutaneous lupus erythematosus subsets.
PMID- 27492813
TI - The many faces of Meckel's diverticulum and its complications.
AB - Meckel's diverticulum is the most frequent congenital malformation of the
gastrointestinal tract, occurring in 2% of the general population. Meckel's
diverticulum is usually asymptomatic and found incidentally. However, the
lifetime risk of complications is 4-40%. In this essay, we describe the clinical
and imaging findings in 12 cases of Meckel's diverticula with complications over
a 5-year period, which were confirmed pathologically. The major complications of
Meckel's diverticulum include gastrointestinal bleeding, bowel obstruction,
perforation and inflammation. Small bowel follow-through (SBFT), computed
tomography (CT) including CT enterography and RI scintigraphy can be used to show
typical imaging features of Meckel's diverticulum and its complications.
Knowledge of the clinical and radiologic findings of Meckel's diverticulum can
aid in the early and accurate diagnosis of this anomaly and its complications.
PMID- 27492814
TI - One-pot construction of fused polycyclic heteroarenes involving 7-azaindoles and
alpha,beta-unsaturated ketones.
AB - A novel one-pot synthesis of pi-conjugated polycyclic compounds, which could
undergo further facile transformation to form complex polycyclic heteroarene
compounds, has been realized between 7-azaindoles and alpha,beta-unsaturated
ketones. This distinctive cascade process proceeds via a rhodium(iii)-catalyzed
alkylation/copper-catalyzed radical annulation-aromatization pathway.
PMID- 27492816
TI - Community participation of youth with intellectual disability and autism spectrum
disorder.
AB - BACKGROUND: Community participation is associated with a range of positive
developmental outcomes; however, the frequency, depth and resources associated
with participation for youth with intellectual disability (ID) and autism
spectrum disorder (ASD) are not well understood. METHOD: Caregivers of 212 youth
with ASD and ID and only ID, aged 11-22 years, completed an online survey.
Comparisons were made of caregiver reports of diversity and frequency of
participation, levels of participation involvement and related environmental
barriers and supports. RESULTS: The diversity and frequency of community
participation of youth with ASD and ID approximated that of youth with ID only.
Youth with ASD and ID were reported to be significantly less involved in the
community activities in which they participated. Environmental features, and in
particular, the social demands of community-based activities, were significant
barriers to youths' participation. CONCLUSIONS: The current study highlights
individual and environmental factors amenable to intervention that may foster
successful community participation among youth with ASD and ID.
PMID- 27492818
TI - Bridging the Gap Between Speech and Language: Using Multimodal Treatment in a
Child With Apraxia.
AB - Childhood apraxia of speech is a neurologic speech sound disorder in which
children have difficulty constructing words and sounds due to poor motor planning
and coordination of the articulators required for speech sound production. We
report the case of a 3-year-old boy strongly suspected to have childhood apraxia
of speech at 18 months of age who used multimodal communication to facilitate
language development throughout his work with a speech language pathologist. In
18 months of an intensive structured program, he exhibited atypical rapid
improvement, progressing from having no intelligible speech to achieving age
appropriate articulation. We suspect that early introduction of sign language by
family proved to be a highly effective form of language development, that when
coupled with intensive oro-motor and speech sound therapy, resulted in rapid
resolution of symptoms.
PMID- 27492815
TI - Atrial fibrillation driver mechanisms: Insight from the isolated human heart.
AB - Although there have been great technological advances in the treatment of atrial
fibrillation (AF), current therapies remain limited due to a narrow understanding
of AF mechanisms in the human heart. This review will highlight our recent
studies on explanted human hearts where we developed and employed a novel
functional-structural mapping approach by integrating high-resolution
simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium
enhanced MRI to define the spatiotemporal characteristics of AF drivers and their
structural substrates. The results allow us to postulate that the primary
mechanism of AF maintenance in human hearts is a limited number of localized
intramural microanatomic reentrant AF drivers anchored to heart-specific 3D
fibrotically insulated myobundle tracks, which may remain hidden to clinical
single-surface electrode mapping. We suggest that ex vivo human heart studies, by
using an integrated 3D functional and structural mapping approach, will help to
reveal defining features of AF drivers as well as validate and improve clinical
approaches to detect and target these AF drivers in patients with cardiac
diseases.
PMID- 27492817
TI - Discontinuation and Nonpublication of Randomized Clinical Trials Conducted in
Children.
AB - BACKGROUND: Trial discontinuation and nonpublication represent potential waste in
research resources and lead to compromises in medical evidence. Pediatric trials
may be particularly vulnerable to these outcomes given the challenges encountered
in conducting trials in children. We aimed to determine the prevalence of
discontinuation and nonpublication of randomized clinical trials (RCTs) conducted
in pediatric populations. METHODS: Retrospective, cross-sectional study of
pediatric RCTs registered in ClinicalTrials.gov from 2008 to 2010. Data were
collected from the registry and associated publications identified (final search
on September 1, 2015). RESULTS: Of 559 trials, 104 (19%) were discontinued early,
accounting for an estimated 8369 pediatric participants. Difficulty with patient
accrual (37%) was the most commonly cited reason for discontinuation. Trials were
less likely to be discontinued if they were funded by industry compared with
academic institutions (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27
0.77). Of the 455 completed trials, 136 (30%) were not published, representing 69
165 pediatric participants. Forty-two unpublished trials posted results on
ClinicalTrials.gov. Trials funded by industry were more than twice as likely to
result in nonpublication at 24 and 36 months (OR 2.21, 95% CI 1.35-3.64; OR 3.12,
95% CI 1.6-6.08, respectively) and had a longer mean time to publication compared
with trials sponsored by academia (33 vs 24 months, P < .001). CONCLUSIONS: In
this sample of pediatric RCTs, discontinuation and nonpublication were common,
with thousands of children exposed to interventions that did not lead to
informative or published findings. Trial funding source was an important
determinant of these outcomes, with both academic and industry sponsors
contributing to inefficiencies.
PMID- 27492819
TI - Suppression of miR-19b enhanced the cytotoxic effects of mTOR inhibitors in human
neuroblastoma cells.
AB - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors exert significant
antitumor effects on several cancer cell types. In this study, we investigated
the effects of mTOR inhibitors, in particular the regulation of the microRNA, in
neuroblastoma cells. METHODS: AZD8055 (a new mTOR inhibitor)- or rapamycin
induced cytotoxic effects on neuroblastoma cells were studied. Western blotting
was used to investigate the expression of various proteins in the mTOR pathway.
MicroRNA precursors and antagomirs were transfected into cells to manipulate the
expression of target microRNA. RESULTS: AZD8055 exerted stronger cytotoxic
effects than rapamycin in neuroblastoma cells (p<0.03). In addition, AZD8055
suppressed the mTOR pathway and increased the expression of phosphatase and
tensin homolog deleted on chromosome 10 (PTEN) in the neuroblastoma cells.
AZD8055 significantly decreased miR-19b expression (p<0.005); in contrast,
rapamycin increased miR-19b expression (p<0.05). Transfection of miR-19b
antagomir into the neuroblastoma cells mimicked the effects of AZD8055 treatment,
whereas miR-19b overexpression reversed the effects of AZD8055. Combination of
miR-19b knockdown and rapamycin treatment significantly improved the sensitivity
of neuroblastoma cells to rapamycin (p<0.02). CONCLUSION: Suppression of miR-19b
may enhance the cytotoxic effects of mTOR inhibitors in neuroblastoma cells.
PMID- 27492820
TI - Effect of democratic reforms on child mortality: a synthetic control analysis.
AB - BACKGROUND: The effects of political regimes on health are unclear because
empirical evidence is neither strong nor robust. Traditional econometric tools do
not allow the direction of causality to be established clearly. We used a new
method to investigate whether political transition into democracy affected child
mortality. METHODS: We used a synthetic control method to assess the effects of
democratisation on child mortality as a proxy of health in countries that
underwent transition from autocracy to democracy that lasted for at least 10
years between 1960 and 2010. Democracy was indicated by a score greater than 0 in
the Polity2 index. We constructed synthetic controls (counterfactuals) based on
weighted averages for factors such as child mortality, economic development,
openess to trade, conflict, rural population, and female education from a pool of
countries that remained autocracies during the study period. RESULTS: Of 60
countries that underwent democratic transition in the study period, 33 met our
inclusion criteria. We were able to construct good counterfactuals for 24 of
these. On average, democratisation reduced child mortality, and the effect
increased over time. Significant reductions in child mortality were seen in nine
(38%) countries, with the average reduction 10 years after democratisation being
13%. In the other 15 countries the effects were not significant. At the country
level yhe effects were heterogeneous, but the differences did not correlate with
geographic, economic, or political indicators. The effect of democratisation,
however, was stronger in countries with above average child mortality before
transition than in countries with below average child mortality. INTERPRETATION:
Our results are consistent with the interpretation that democratic reforms have
the greatest effects when child mortality is a direct concern for a large part of
the population. Future research could focus on identifying the precise mechanism
through which the effects emerge. FUNDING: European Union 7th Framework Programme
and KU Leuven Methusalem Fund.
PMID- 27492821
TI - Towards parity democracy.
PMID- 27492822
TI - Can pay for performance improve the quality of primary care?
PMID- 27492823
TI - Parenting style and perceptions of children's weight among US Hispanics: a
qualitative analysis.
AB - Parental perceptions of their children's weight status may limit their
willingness to participate in or acknowledge the importance of early
interventions to prevent childhood obesity. This study aimed to examine potential
differences in Hispanic mothers' and fathers' perceptions of childhood obesity,
lifestyle behaviors and communication preferences to inform the development of
culturally appropriate childhood obesity interventions. A qualitative study using
focus groups was conducted. Groups (one for mothers and one for fathers) were
composed of Hispanic parents (n = 12) with at least one girl and one boy (<= 10
years old) who were patients at a pediatric clinic in Tennessee, USA. Thirteen
major themes clustered into four categories were observed: (i) perceptions of
childhood obesity/children's weight; (ii) parenting strategies related to
children's dietary behaviors/physical activity; (iii) perceptions of what parents
can do to prevent childhood obesity and (iv) parental suggestions for partnering
with child care providers to address childhood obesity. Mothers appeared to be
more concerned than fathers about their children's weight. Fathers expressed more
concern about the girls' weight than boys'. Mothers were more likely than fathers
to congratulate their children more often for healthy eating and physical
activity. Parents collectively expressed a desire for child care providers (e.g.
caregivers, teachers, medical professionals and food assistance programs
coordinators) to have a caring attitude about their children, which might in turn
serve as a motivating factor in talking about their children's weight. Parental
perceptions of their children's weight and healthy lifestyle choices are of
potential public health importance since they could affect parental participation
in preventive interventions.
PMID- 27492824
TI - Resilience as a double-edged health promotion goal: examples from Lao PDR.
AB - Individual and community resilience are undoubtedly important targets for health
enhancement and invaluable aspirational outcomes in the health promotion
endeavour especially in disaster contexts. However, overreliance on resilience as
a proxy for positive well-being has serious personal and political implications
in many contexts, as illustrated in research findings on women's quality of life
in southern Lao PDR. Case studies derived from focus group interviews with ethnic
minority Lao women about their quality of life are used to exemplify how overt
signs of resilience may mask, rather than mirror, covert existential reality
leaving women without a voice. The political implications of this silencing are
profound. Private troubles remain hidden rather than being identified as public
issues subject to public policy. This conundrum is not confined to third world
countries. Structural limitations to achieving profound fulfilment abound in
affluent countries also, yet neo-liberal governments rely heavily on the
resilience of populations to minimize public spending. The challenge for health
promotion researchers, policy makers and practitioners is to explore the nexus
between individual agency and structural change in each specific context to
ensure that health promotion initiatives do not inadvertently perpetuate
disparities in access to power and resources.
PMID- 27492825
TI - Unpacking complexity in public health interventions with the Actor-Network
Theory.
AB - This article proposes a sociologically informed theoretical and methodological
framework to address the complexity of public health interventions (PHI). It
first proposes three arguments in favour of using the Actor-Network Theory (ANT)
for the framework. ANT: (1) deals with systems made of human and non-human
entities and proposes a relational view of action; (2) provides an understanding
of the intervention-context interactions and (3) is a tool for opening the
intervention's black box. Three principles derived from ANT addressing
theoretical problems with conceptualisation of PHI as complex systems are
proposed: (1) to focus on the process of connecting the network entities instead
of their stabilised form; (2) both human and non-human entities composing
networks have performative capacities and (3) network and intervention shape one
another. Three methodological guidelines are further derived: (1) the
researcher's task consists in documenting the events that transform the network
and intervention; (2) events must be ordered chronologically to represent the
intervention's evolution and (3) a broad range of data is needed to capture
complex interventions' evolution. Using ANT as a guide, this paper helps
reconcile technicist and social views of PHI and provides a mean to integrate
process and effect studies of interventions.
PMID- 27492826
TI - Proposing a health promotion framework to address gambling problems in Australian
Indigenous communities.
AB - Gambling impacts affect Australian Indigenous families and communities in diverse
and complex ways. Indigenous people throughout Australia engage in a broad range
of regulated and unregulated gambling activities. Challenges in this area include
the complexities that come with delivering services and programmes between the
most remote regions, to highly populated towns and cities of Australia. There is
little knowledge transfer between states and territories in Australia and no
conceptual understanding or analysis of what constitutes 'best practice' in
gambling service delivery for Indigenous people, families and communities. This
article reviews health promotion approaches used in Australia, with a particular
focus on Indigenous and gambling-based initiatives. Contributing to this review
is an examination of health promotion strategies used in Indigenous gambling
service delivery in the Northern Territory, New South Wales and Western
Australia, demonstrating diversity and innovation in approaches. The article
concludes by emphasizing the potential value of adopting health promotion
strategies to underpin programme and service delivery for addressing gambling
problems in Australian Indigenous communities. However, success is contingent on
robust, evidence-based programme design, implementation and evaluation that
adhere to health promotion principles.
PMID- 27492827
TI - Tuberculosis care among refugees arriving in Europe: a ERS/WHO Europe Region
survey of current practices.
AB - No evidence exists on tuberculosis (TB) and latent TB infection (LTBI) management
policies among refugees in European countries.A questionnaire investigating
screening and management practices among refugees was sent to 38 national TB
programme representatives of low and intermediate TB incidence European
countries/territories of the WHO European Region.Out of 36 responding countries,
31 (86.1%) reported screening for active TB, 19 for LTBI, and eight (22.2%)
reporting outcomes of LTBI treatment. Screening for TB is based on algorithms
including different combinations of symptom-based questionnaires, bacteriology
and chest radiography and LTBI screening on different combinations of tuberculin
skin test and interferon-gamma release assays. In 22 (61.1%) countries, TB and
LTBI screening are performed in refugee centres. In 22 (61.1%) countries, TB
services are organised in collaboration with the private sector. 27 (75%)
countries answered that screening for TB is performed as per national and
international guidelines, while 19 (52.7%) gave the same answer with regards to
LTBI screening. Infection control measures are inadequate in several of the
countries surveyed.There is need for improved coordination of TB screening in
Europe to implement the End TB Strategy and achieve TB elimination.
PMID- 27492828
TI - Mechanisms of exertional dyspnoea in symptomatic smokers without COPD.
AB - Dyspnoea and activity limitation can occur in smokers who do not meet spirometric
criteria for chronic obstructive pulmonary disease (COPD) but the underlying
mechanisms are unknown.Detailed pulmonary function tests and sensory-mechanical
relationships during incremental exercise with respiratory pressure measurements
and diaphragmatic electromyography (EMGdi) were compared in 20 smokers without
spirometric COPD and 20 age-matched healthy controls.Smokers (mean+/-sd post
bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity 75+/
4%, mean+/-sd FEV1 104+/-14% predicted) had greater activity-related dyspnoea,
poorer health status and lower physical activity than controls. Smokers had
peripheral airway dysfunction: higher phase-III nitrogen slopes (3.8+/-1.8 versus
2.6+/-1.1%.L(-1)) and airway resistance (difference between airway resistance
measured at 5 Hz and 20 Hz 19+/-11 versus 12+/-7% at 5 Hz) than controls
(p<0.05). Smokers had significantly (p<0.05) lower peak oxygen uptake (78+/-40
versus 107+/-45% predicted) and ventilation (61+/-26 versus 97+/-29 L.min(-1)).
Exercise ventilatory requirements, operating lung volumes and cardio-circulatory
responses were similar. However, submaximal dyspnoea ratings, resistive and total
work of breathing were increased in smokers compared with controls (p<0.05);
diaphragmatic effort (transdiaphragmatic pressure/maximumal transdiaphragmatic
pressure) and fractional inspiratory neural drive to the diaphragm (EMGdi/maximal
EMGdi) were also increased (p<0.05) mainly reflecting the reduced
denominator.Symptomatic smokers at risk for COPD had greater exertional dyspnoea
and lower exercise tolerance compared with healthy controls in association with
greater airways resistance, contractile diaphragmatic effort and fractional
inspiratory neural drive to the diaphragm.
PMID- 27492829
TI - Clinical manifestations in primary ciliary dyskinesia: systematic review and meta
analysis.
AB - Few original studies have described the prevalence and severity of clinical
symptoms of primary ciliary dyskinesia (PCD). This systematic review and meta
analysis aimed to identify all published studies on clinical manifestations of
PCD patients, and to describe their prevalence and severity stratified by age and
sex.We searched PubMed, Embase and Scopus for studies describing clinical
symptoms of >=10 patients with PCD. We performed meta-analyses and meta
regression to explain heterogeneity.We included 52 studies describing a total of
1970 patients (range 10-168 per study). We found a prevalence of 5% for
congenital heart disease. For the rest of reported characteristics, we found
considerable heterogeneity (I2 range 68-93.8%) when calculating the weighted mean
prevalence. Even after taking into account the explanatory factors, the largest
part of the between-studies variance in symptom prevalence remained unexplained
for all symptoms. Sensitivity analysis including only studies with test-proven
diagnosis showed similar results in prevalence and heterogeneity.Large
differences in study design, selection of study populations and definition of
symptoms could explain the heterogeneity in symptom prevalence. To better
characterise the disease, we need larger, multicentre, multidisciplinary,
prospective studies that include all age groups, use uniform diagnostics and
report on all symptoms.
PMID- 27492830
TI - Predictive value of exhaled nitric oxide in the management of asthma: a
systematic review.
AB - The clinical value of measuring fractional exhaled nitric oxide (FeNO) in asthma
is not clear. We aimed to assess whether FeNO can reliably predict clinical
outcomes in asthma treated with inhaled corticosteroids (ICS). We also evaluated
whether its predictive role is influenced by different inflammatory phenotypes of
asthma.We conducted a systematic review focusing on five clinically relevant
questions. Two authors independently screened search results, extracted data and
assessed quality of the included studies. Data were synthesised by qualitative
methods.12 prospective studies were included, answering partly three of the five
questions. In steroid-naive asthma, a high FeNO level probably predicts good
response to ICS. In ICS-treated asthmatics, a low FeNO level probably predicts
low risk of exacerbation, and the patient is unlikely to benefit from increasing
ICS dose. There were scarce data to conclude whether FeNO predicts exacerbations
when ICS treatment is stopped in well-controlled asthma. Only one study reported
results separately in different asthma phenotypes.The current evidence on the
predictive value of FeNO and its role in the management of asthma is incomplete.
Future studies should focus on clinically meaningful questions and probably
target only eosinophilic phenotypes where FeNO is best associated with the
activity of airway inflammation.
PMID- 27492831
TI - Air pollution exposure is associated with restrictive ventilatory patterns.
PMID- 27492832
TI - Blood granulocyte patterns as predictors of asthma phenotypes in adults from the
EGEA study.
AB - To what extent blood granulocyte patterns may predict asthma control remains
under-studied. Our aim was to study associations between blood neutrophilia and
eosinophilia and asthma control outcomes in adults.Analyses were conducted in 474
asthmatics from the first follow-up of the Epidemiological Study on the Genetics
and Environment of Asthma (EGEA2), including 242 asthmatics who were adults a
decade earlier (EGEA1). At EGEA2, asthma control was assessed using the Global
Initiative for Asthma definition (2015), and asthma exacerbations by use of
urgent care or courses of oral corticosteroids in the past year. Blood
EOSlo/EOShi was defined as >=250 eosinophils.mm-3, respectively, and
NEUlo/NEUhi as >=5000 neutrophils.mm-3, respectively. Estimates were adjusted
for age, sex and smoking.At EGEA2, NEUhi was associated with asthma exacerbations
and poor asthma control (OR >2.10). EOShi was associated with higher bronchial
hyperresponsiveness (BHR) (OR (95% CI) 2.21 (1.24-3.97)), poor lung function
(p=0.02) and higher total IgE level (p=0.002). Almost 50% of asthmatics had a
persistent pattern between surveys. Persistent NEUhi was associated with poor
asthma control at EGEA2 (OR (95% CI) 3.09 (1.18-7.05)). EOShi at EGEA1 and
persistent EOShi were associated with higher BHR (OR (95% CI) 2.36 (1.10-5.07)
and 3.85 (1.11-13.34), respectively), poor lung function (p<0.06) and higher
immunoglobulin E level (p<10-4) at EGEA2.Granulocyte patterns were differently
associated with asthma outcomes, suggesting specific roles for each one, which
could be tested as predictive signatures.
PMID- 27492833
TI - Efficacy and safety of aclidinium/formoterol versus salmeterol/fluticasone: a
phase 3 COPD study.
AB - The efficacy and safety of twice-daily aclidinium bromide/formoterol fumarate was
compared with that of salmeterol/fluticasone propionate in patients with stable,
moderate-to-severe chronic obstructive pulmonary disease (COPD).AFFIRM COPD
(Aclidinium and Formoterol Findings in Respiratory Medicine COPD) was a 24-week,
double-blind, double-dummy, active-controlled study. Patients were randomised
(1:1) to aclidinium/formoterol 400/12 ug twice-daily via Genuair/Pressair or
salmeterol/fluticasone 50/500 ug twice-daily via Accuhaler. The primary end-point
was peak forced expiratory volume in 1 s (FEV1) at week 24. Other end-points
included Transition Dyspnoea Index (TDI) focal score at week 24, TDI and St
George's Respiratory Questionnaire (SGRQ) responders, COPD Assessment Test and
SGRQ scores, assessment of COPD symptoms and exacerbations, use of reliever
medication, and device preference. Adverse events were monitored throughout.In
total, 933 patients were eligible (mean age 63.4 years, 65.1% male).
Aclidinium/formoterol was superior to salmeterol/fluticasone in peak FEV1 and
noninferior in TDI. Health status and reduction in exacerbation risk were similar
in both groups. While both treatments were well tolerated, pneumonia occurred
less frequently with aclidinium/formoterol than salmeterol/fluticasone.In stable
COPD, aclidinium/formoterol significantly improved bronchodilation versus
salmeterol/fluticasone, with equivalent benefits in symptom control and reduction
in exacerbation risk. Both treatments were well tolerated and treatment-related
adverse events were less common with aclidinium/formoterol.
PMID- 27492834
TI - The emerging role of epigenetics in pulmonary hypertension.
AB - Epigenetics is usually defined as the study of changes in phenotype and gene
expression not related to sequence alterations, but rather the chemical
modifications of DNA and of its associated chromatin proteins. These
modifications can be acquired de novo, being inherited, and represent the way in
which genome and environment interact. Recent evidence points to the involvement
of epigenetic changes in the pathogenesis of pulmonary hypertension, as they can
partly explain how environmental and lifestyle factors can impose susceptibility
to pulmonary hypertension and can explain the phenotypic alteration and
maintenance of the disease state.In this article, we review the epigenetic
regulatory mechanisms that are mediated by DNA methylation, the post
translational modifications of histone tails and noncoding RNAs in the
pathogenesis of pulmonary hypertension. Furthermore, pharmacological
interventions aimed at epigenetic regulators/modifiers and their outcomes in
different cellular and preclinical rodent models are discussed. Lastly, the
remaining challenges and future directions in which to explore epigenetic-based
therapies in pulmonary hypertension are discussed.
PMID- 27492835
TI - Laparoscopic anti-reflux surgery for idiopathic pulmonary fibrosis at a single
centre.
AB - We sought to assess whether laparoscopic anti-reflux surgery (LARS) is associated
with decreased rates of disease progression in patients with idiopathic pulmonary
fibrosis (IPF).The study was a retrospective single-centre study of IPF patients
with worsening symptoms and pulmonary function despite antacid treatment for
abnormal acid gastro-oesophageal reflux. The period of exposure to LARS was
September 1998 to December 2012. The primary end-point was a longitudinal change
in forced vital capacity (FVC) % predicted in the pre- versus post-surgery
periods.27 patients with progressive IPF underwent LARS. At time of surgery, the
mean age was 65 years and mean FVC was 71.7% pred. Using a regression model, the
estimated benefit of surgery in FVC % pred over 1 year was 5.7% (95% CI -0.9
12.2%, p=0.088) with estimated benefit in FVC of 0.22 L (95% CI -0.06-0.49 L,
p=0.12). Mean DeMeester scores decreased from 42 to 4 (p<0.01). There were no
deaths in the 90 days following surgery and 81.5% of participants were alive 2
years after surgery.Patients with IPF tolerated the LARS well. There were no
statistically significant differences in rates of FVC decline pre- and post-LARS
over 1 year; a possible trend toward stabilisation in observed FVC warrants
prospective studies. The ongoing prospective randomised controlled trial will
hopefully provide further insights regarding the safety and potential efficacy of
LARS in IPF.
PMID- 27492836
TI - Dosage of isoniazid and rifampicin poorly predicts drug exposure in tuberculosis
patients.
PMID- 27492838
TI - Task for Today: Complete the Puzzle of Circulating Stem Cells and the
Atherosclerotic Burden.
PMID- 27492837
TI - Diagnosing primary ciliary dyskinesia: an international patient perspective.
AB - Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterised by
progressive sino-pulmonary disease, with symptoms starting soon after birth. A
European Respiratory Society (ERS) Task Force aims to address disparities in
diagnostics across Europe by providing evidence-based clinical practice
guidelines. We aimed to identify challenges faced by patients when referred for
PCD diagnostic testing.A patient survey was developed by patient representatives
and healthcare specialists to capture experience. Online versions of the survey
were translated into nine languages and completed in 25 countries. Of the
respondents (n=365), 74% were PCD-positive, 5% PCD-negative and 21% PCD
uncertain/inconclusive. We then interviewed 20 parents/patients. Transcripts were
analysed thematically.35% of respondents visited their doctor more than 40 times
with PCD-related symptoms prior to diagnostic referral. Furthermore, the most
prominent theme among interviewees was a lack of PCD awareness among medical
practitioners and failure to take past history into account, leading to delayed
diagnosis. Patients also highlighted the need for improved reporting of results
and a solution to the "inconclusive" diagnostic status.These findings will be
used to advise the ERS Task Force guidelines for diagnosing PCD, and should help
stakeholders responsible for improving existing services and expanding provision
for diagnosis of this rare disease.
PMID- 27492839
TI - The All-Chemical Approach: A Solution for Converting Fibroblasts Into Myocytes.
PMID- 27492840
TI - Karin Bornfeldt: Sticking With a Complicated Problem.
PMID- 27492841
TI - Adaptions to Hypoxia and Redox Stress: Essential Concepts Confounded by
Misleading Terminology.
PMID- 27492843
TI - Correction.
PMID- 27492842
TI - Responder Definition in Clinical Stem Cell Trials in Cardiology: Will the Real
Responder Please Stand Up?
PMID- 27492844
TI - Unusual FDG uptakes of mesenteric brown adipose tissue in a patient with
pheochromocytomas.
PMID- 27492845
TI - Synchronous presentation of nasopharyngeal carcinoma and abdominal paraganglioma
with avid 18F-FDG and 68Ga-DOTA-TOC uptake in PET/CT by both tumours.
PMID- 27492846
TI - Model averaging inconcentration-QT analyses.
AB - This article describes how a frequentist model averaging approach can be used for
concentration-QT analyses in the context of thorough QTc studies. Based on
simulations, we have concluded that starting from three candidate model families
(linear, exponential, and Emax) the model averaging approach leads to treatment
effect estimates that are quite robust with respect to the control of the type I
error in nearly all simulated scenarios; in particular, with the model averaging
approach, the type I error appears less sensitive to model misspecification than
the widely used linear model. We noticed also few differences in terms of
performance between the model averaging approach and the more classical model
selection approach, but we believe that, despite both can be recommended in
practice, the model averaging approach can be more appealing because of some
deficiencies of model selection approach pointed out in the literature. We think
that a model averaging or model selection approach should be systematically
considered for conducting concentration-QT analyses. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27492847
TI - Nanocrystalline calcium sulfate/hydroxyapatite biphasic compound as a TGF
beta1/VEGF reservoir for vital pulp therapy.
AB - OBJECTIVES: Vital pulp therapy aims to treat reversible pulpal injuries via
protective dentinogenesis and to preserve more tooth structure. Mineral trioxide
aggregate (MTA)-based capping materials demonstrate prolonged setting time
increases the risk of pulpal infection during multi-visit treatment. Their non
degradable property occupies pulp space and limits dentin-pulp regeneration. This
study reports an inorganic degradable biomaterial that presents a short initial
setting time and acts as a growth factor reservoir to promote reparative
dentinogenesis. METHODS: We synthesize nanocrystalline calcium sulfate
hemihydrate (nCS), hydroxyapatite (HAp) and calcium sulfate hemihydrate (CS) as a
reservoir to which transforming growth factor-beta 1 (TGF-beta1) and vascular
endothelial growth factor (VEGF) are added (denoted as nCS/HAp/CS/TGF
beta1/VEGF). In vitro biocompatibility and mineralization (the activity and
expression of alkaline phosphatase, ALP) were evaluated. Rat animal model was
created to test in vivo efficacy. RESULTS: Cultured human dental pulp cells
(HDPCs) showed that nCS/HAp/CS/TGF-beta1/VEGF cement has excellent
biocompatibility and the potential to elevate the activity and expression of ALP.
The in vivo efficacy (rat animal model) indicates protective dentin by micro
computed tomography (MU-CT) measurements and histological analyses. The 3D MU-CT
non-destructive analysis also determines volume changes during pulpotomy,
suggesting that the degraded space of the nCS/HAp/CS/TGF-beta1/VEGF cement is
repaired by the formation of dentin-pulp tissue. SIGNIFICANCE: These findings
demonstrate that nCS/HAp/CS cement acts as a potent reservoir for the sustained
release of growth factors, and that nCS/HAp/CS/TGF-beta1/VEGF cement has a high
potential to form the reparative dentinogenesis in vivo.
PMID- 27492848
TI - Findings in Historical Control Harlan RCCHanTM: WIST Rats from 104-week Oral
Gavage Studies.
AB - Vehicle control Harlan RCCHanTM:WIST rats were examined to provide control data
for subsequent studies. The rats (180 male and 180 female) were dosed daily via
oral gavage with reverse osmosis water for up to 104 weeks. At necropsy, body
weights and macroscopic findings were recorded and tissues were collected for
histopathology. The mean body weight at terminal sacrifice was 687 g for males
and 466 g for females. The overall survival rate was 62% for males and 59% for
females. The most common cause of death for males and females found dead or
examined following unscheduled euthanasia was pituitary neoplasia with an
incidence of 13.9% for males and 18.9% for females. Macroscopic and neoplastic
and nonneoplastic microscopic findings are presented by body system.
PMID- 27492849
TI - Aluminium ion-promoted radical-scavenging reaction of methylated hydroquinone
derivatives.
AB - The effect of the aluminium ion (Al(3+)) on the scavenging reaction of a 2,2
diphenyl-1-picrylhydrazyl radical (DPPH), as a reactivity model of reactive
oxygen species, with hydroquinone (QH2) and its methylated derivatives (MenQH2, n
= 1-4) was investigated using stopped-flow and electrochemical techniques in a
hydroalcoholic medium. The second-order rate constants (k) for the DPPH
scavenging reaction of the hydroquinones increased with the increasing number of
methyl substituents. Upon addition of Al(3+), the k values significantly
increased depending on the concentration of Al(3+). Such an accelerating effect
of Al(3+) on the DPPH-scavenging rates of the hydroquinones results from the
remarkable positive shift of the one-electron reduction potential (Ered) of DPPH
in the presence of Al(3+). These results demonstrate that Al(3+), a strong Lewis
acid, can act as a radical-scavenging promoter by stabilising the one-electron
reduced species of the radical, although Al(3+) is reported not only to act as a
pro-oxidant but also to strongly interact with biomolecules, showing toxicities.
PMID- 27492850
TI - Aetiology of in-hospital cardiac arrest on general wards.
AB - AIM: Aetiology of in-hospital cardiac arrests (IHCAs) on general wards has not
been studied. We aimed to determine the underlying causes for IHCAs by the means
of autopsy records and clinical judgement of the treating consultants.
Furthermore, we investigated whether aetiology and preceding vital dysfunctions
are associated with long-term survival. DESIGN AND SETTING: Prospective
observational study between 2009-2011 including 279 adult IHCA patients attended
by medical emergency team in a Finnish university hospital's general wards.
RESULTS: The median age of the patients was 72 (64, 80) years, 185 (66%) were
male, 178 (64%) of events were monitored/witnessed, first rhythm was shockable in
42 (15%) cases and 53 (19%) patients survived six months. Aetiology was
determined as cardiac in 141 events, 73 of which were due to acute myocardial
infarction. There were 138 non-cardiac IHCAs; most common causes were pneumonia
(39) and exsanguination (16). No statistical difference was observed in the
incidence of objective vital dysfunctions preceding the event between the cardiac
and non-cardiac groups (40% vs. 44%, p=0.448). Subjective antecedents were more
common in the cardiac cohort (47% vs. 32%, p=0.022), chest pain being an example
(11% vs. 0.7%, p<0.001). Reviewing all 279 IHCAs, only shockable primary rhythm,
monitored/witnessed event and low comorbidity score were independently associated
with 180-day survival. CONCLUSIONS: Cardiac aetiology underlies half of the IHCAs
on general wards. Both objective and subjective antecedents are common. However,
neither the cardiac aetiology nor the absence of preceding deterioration of vital
signs were factors independently associated with a favourable outcome.
PMID- 27492851
TI - Examining emotion regulation in depression: A review and future directions.
AB - Major Depressive Disorder (MDD) is an affective disorder with sustained negative
affect and difficulties experiencing positive affect as its hallmark features.
Previous work also highlights cognitive biases and deficits in cognitive control
that accompany depression and suggestions have been made as to how cognitive and
affective aspects of the disorder are linked. Recent work proposes that
difficulties in the self-regulation of affect after experiencing negative life
events may contribute to risk for the onset of depression, and indeed there is
evidence that depressed patients exhibit more frequent use of maladaptive
strategies when regulating affect and show difficulties effectively implementing
adaptive strategies. Cognitive aspects of depression may play an important role
in helping us understand these difficulties in self-regulation. This article
reviews recent work on emotion regulation in depression and links cognitive
biases and deficits associated with depression to difficulties in the self
regulation of emotion. Importantly, a main goal of the article is to identify
topics in need of future attention that could greatly help shed light on the
relation between cognition and emotion regulation in this and other psychological
disorders.
PMID- 27492852
TI - Yttrium Siloxide Complexes Bearing Terminal Methyl Ligands: Molecular Models for
Ln-CH3 Terminated Silica Surfaces.
AB - Surface organometallic chemistry (SOMC) on silica materials is a prominent
approach for the generation of highly active heterogenized polymerization
catalysts. Despite advanced methods of characterization, the elucidation of the
catalytically active surface species remains a challenging task. Alkylated rare
earth metal siloxide complexes can be regarded as molecular models of respective
covalently bonded alkylated surface species, primarily used for 1,3-diene
polymerization. Here, we performed both salt metathesis reactions of [Y(MMe4 )3 ]
(M = Al, Ga) with [K{OSi(OtBu)3 }] and alkylation reactions of [Y{OSi(OtBu)3 }3
]2 with AlMe3 . The obtained complexes [Y(CH3 )[(AlMe2 ){OSi(OtBu)3 }2 ](AlMe4
)]2 , [Y(CH3 )[(AlMe2 ){OSi(OtBu)3 }2 ]-{OSi(OtBu)3 }], [Y{OSi(OtBu)3 }3 (MU
Me)Y(MU-Me)2 Y{OSi(OtBu)3 }2 (AlMe4 )], and [Y(CH3 )(GaMe4 ){OSi(OtBu)3 }]2
represent rare examples of organoyttrium species with terminal methyl groups. The
formation and purity of the mixed methyl/siloxy yttrium complexes could be
enhanced by treating [Y(MMe4 )3 ] with [K(MMe2 ){OSi(OtBu)3 }2 ]n (M=Al: n=2;
M=Ga: n=infinity). Complexes [K(MMe2 ){OSi(OtBu)3 }2 ]n were obtained by addition
of [K{OSi(OtBu)3 }] to [Me2 M{OSi(OtBu)3 }]2 . Deeper insight into the fluxional
behavior of the mixed methyl/siloxy yttrium complexes in solution was gained by
(1) H and (13) C NMR spectroscopic studies at variable temperature and (1) H-(89)
Y HSQC NMR spectroscopy.
PMID- 27492853
TI - Retargeted adenoviruses for radiation-guided gene delivery.
AB - The combination of radiation with radiosensitizing gene delivery or oncolytic
viruses promises to provide an advantage that could improve the therapeutic
results for glioblastoma. X-rays can induce significant molecular changes in
cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78
kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma
membranes of irradiated cancer cells and tumor-associated microvascular
endothelial cells. The goal of our study was to improve tumor-specific adenovirus
mediated gene delivery by selectively targeting the adenovirus binding to this
radiation-inducible protein. We employed an adenoviral fiber replacement approach
to conduct a study of the targeting utility of GRP78-binding peptide. We have
developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted
into the fiber-fibritin. We have evaluated the reporter gene expression of fiber
modified adenoviruses in vitro using a panel of glioma cells and a human D54MG
tumor xenograft model. The obtained results demonstrated that employment of the
GRP78-binding peptide resulted in increased gene expression in irradiated tumors
following infection with fiber-modified adenoviruses, compared with untreated
tumor cells. These studies demonstrate the feasibility of adenoviral retargeting
using the GRP78-binding peptide that selectively recognizes tumor cells
responding to radiation treatment.
PMID- 27492854
TI - Overexpression of angiopoietin 2 promotes the formation of oral squamous cell
carcinoma by increasing epithelial-mesenchymal transition-induced angiogenesis.
AB - Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and
neck and is associated with a high rate of lymph node metastasis. The initial
step in the metastasis and transition of tumors is epithelial-mesenchymal
transition (EMT)-induced angiogenesis, which can be mediated by angiopoietin 2
(ANG2), a key regulatory factor in angiogenesis. In the present study,
immunohistochemistry and real-time quantitative reverse transcriptase (qRT-PCR)
were used to measure the expression of ANG2 in OSCC tissues. Plasmids encoding
ANG2 mRNA were used for increased ANG2 expression in the OSCC cell line TCA8113.
The short interfering RNA (siRNA)-targeting ANG2 mRNA sequences were used to
inhibit ANG2 expression in TCA8113 cells. Subsequently, transwell assays were
performed to examine the effects of ANG2 on TCA8113 cell migration and invasion.
Furthermore, in vivo assays were performed to assess the effect of ANG2 on tumor
growth. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)
assays and immunohistochemistry were used to examine cell apoptosis and
angiogenesis in tumor tissues, respectively. Finally, western blot analysis was
performed to evaluate tumor formation-related proteins in OSCC tissues. We found
that protein expression of ANG2 was remarkably upregulated in OSCC tissues.
Overexpression of ANG2 increased the migration and invasion of TCA8113 cells by
regulating EMT. Further investigations showed that overexpression of ANG2
increased tumor growth in nude mice, and angiogenesis of OSCC tissues increased
in the presence of ANG2 overexpression. Overexpression of ANG2 also reduced cell
apoptosis in tumor tissue cells. Finally, we found that overexpression of ANG2
resulted in changes in the expression of tumor formation-related proteins
including vimentin, E-cadherin, Bim, PUMA, Bcl-2, Bax, Cyclin D1, PCNA and CD31.
Our findings show that ANG2 has an important role in the migration and invasion
of OSCC. More importantly, further investigations suggested that overexpression
of ANG2 might increase OSCC metastasis by promoting angiogenesis in nude mice.
This stimulatory effect could be achieved by inducing abnormal EMT and by
reducing apoptosis and increasing proliferation of cells.
PMID- 27492855
TI - Identification and characterization of novel natural pathogen of Drosophila
melanogaster isolated from wild captured Drosophila spp.
AB - Drosophila melanogaster is an emerging model system for the study of evolutionary
ecology of immunity. However, a large number of studies have used non natural
pathogens as very few natural pathogens have been isolated and identified. Our
aim was to isolate and characterize natural pathogen/s of D. melanogaster. A
bacterial pathogen was isolated from wild caught Drosophila spp., identified as a
new strain of Staphylococcus succinus subsp. succinus and named PK-1. This strain
induced substantial mortality (36-62%) in adults of several laboratory
populations of D. melanogaster. PK-1 grew rapidly within the body of the flies
post infection and both males and females had roughly same number of colony
forming units. Mortality was affected by mode of infection and dosage of the
pathogen. However mating status of the host had no effect on mortality post
infection. Given that there are very few known natural bacterial pathogens of D.
melanogaster and that PK-1 can establish a sustained infection across various
outbred and inbred populations of D. melanogaster this new isolate is a potential
resource for future studies on immunity.
PMID- 27492856
TI - Diagnostic value of 18F-FDG PET/cardiac CT in late prosthetic aortic endocarditis
with periprosthetic abscess.
PMID- 27492857
TI - Usefulness of 18F-FDG PET/CT in a case of suspected vascular graft infection.
AB - Vascular prosthetic graft infection (VPGI) is associated with high mortality and
morbidity. An early and accurate diagnosis is essential in order to give the most
appropriate treatment. The case is presented of a 74 year old male subjected to
an aortobifemoral bypass graft, with clinical suspicion of VPGI with inconclusive
tests. Later on an 18F-FDG PET/CT study showed a pathological uptake, suggestive
of periprosthetic infection, as well as an incidental pulmonary lesion,
suggestive of a primary neoplasm. A new 18F-FDG PET/CT showed a significant
improvement in the uptake by the vascular graft after prolonged antibiotic
treatment. 18F-FDG is a promising tracer for detecting VPGI as the accumulated
activated white cells at the infection site have a high demand for 18F-FDG, and
could help define the response to antibiotic treatment.
PMID- 27492858
TI - Sleep and Social-Emotional Development in Infants and Toddlers.
AB - The aim of this study was to examine the cross-sectional and longitudinal
relationships among variables related to sleep patterns and both social-emotional
problems (i.e., internalizing, externalizing, and dysregulation) and healthy
social development (i.e., social competence). Assessments were completed at 6,
12, and 18 months across 5 cohorts of children for a total of 117 mother-child
dyads. Mothers completed the Brief Infant Sleep Questionnaire at 6, 12, and 18
months, as well as the Infant Toddler Social Emotional Assessment at 12 and 18
months. Later bedtimes and less total sleep across the 24-hr period predicted
higher internalizing problem scores, which includes indices of
depression/withdrawal, general anxiety, separation distress, and inhibition. In
contrast, sleep fragmentation was minimally associated with decreased social
competence but not with any negative social-emotional outcomes. These results
indicate that sleep patterns, primarily later bedtimes and less total sleep,
appear to be associated with and predictive of social-emotional problem areas,
namely, internalizing issues, in infants and toddlers. These findings add to the
growing literature on the role of sleep in early social-emotional development and
suggest that sleep schedule and duration should be addressed in clinical
assessment and interventions for infant sleep.
PMID- 27492859
TI - Interstitial microwave treatment for cancer: historical basis and current
techniques in antenna design and performance.
AB - The use of microwaves (MW) for thermal cancer treatment began in the late 1970s.
At first, hyperthermia was induced by using single antennas applied
interstitially. This was followed by arrays of multiple interstitial antennas
driven synchronously at 915 or 2450 MHz. This early work focused on hyperthermia
as an adjuvant therapy, but more recently has evolved into a thermally ablative
monotherapy. Increased power required to thermally ablate tissues required
additional developments such as internally cooled antennas. Larger tumours have
also been ablated with MW antenna arrays activated synchronously or non
synchronously. Numerical modelling has provided clinical treatment planning
guidance and device design insight throughout this history. MW thermal therapy
systems, treatment planning, navigation and image guidance continue to evolve to
provide better tools and options for clinicians and patients in order to provide
targeting optimisation with the goal of improved treatment for the patient and
durable cancer eradication. This paper reviews the history and related
technological developments, including antenna design, of MW heating for both
hyperthermia and ablation.
PMID- 27492860
TI - Pharmacy density in rural and urban communities in the state of Oregon and the
association with hospital readmission rates.
AB - OBJECTIVES: To characterize the pharmacy density in rural and urban communities
with hospitals and to examine its association with readmission rates. DESIGN:
Ecologic study. SETTING: Forty-eight rural and urban primary care service areas
(PCSAs) in the state of Oregon. PARTICIPANTS: All hospitals in the state of
Oregon. INTERVENTION: Pharmacy data were obtained from the Oregon Board of
Pharmacy based on active licensure. Pharmacy density was calculated by
determining the cumulative number of outpatient pharmacy hours in a PCSA. MAIN
OUTCOME MEASURES: Oregon hospital 30-day all-cause readmission rates were
obtained from the Centers for Medicare and Medicaid Services and were determined
with the use of claims data of patients 65 years of age or older who were
readmitted to the hospital within 30 days from July 2012 to June 2013. RESULTS:
Readmission rates for Oregon hospitals ranged from 13.5% to 16.5%. The cumulative
number of pharmacy hours in PCSAs containing a hospital ranged from 54 to 3821
hours. As pharmacy density increased, the readmission rates decreased,
asymptotically approaching a predicted 14.7% readmission rate for areas with high
pharmacy density. CONCLUSION: Urban hospitals were in communities likely to have
more pharmacy access compared with rural hospitals. Future research should
determine if increasing pharmacy access affects readmission rates, especially in
rural communities.
PMID- 27492862
TI - Influence of low-temperature nitriding on the strain-induced martensite and laser
quenched austenite in a magnetic encoder made from 304L stainless steel.
AB - We have investigated the possibility of producing a magnetic encoder by an
innovative process. Instead of turning grooves in the encoder bar for precise
positioning, we incorporated the information in 304L stainless steel by
transforming the austenite to martensite after bar extrusion in liquid nitrogen
and marking it with a laser, which caused a local transformation of martensite
back into austenite. 304L has an excellent corrosion resistance, but a low
hardness and poor wear resistance, which limits its range of applications.
However, nitriding is a very promising way to enhance the mechanical and magnetic
properties. After low-temperature nitriding at 400 degrees C it is clear that
both epsilon- and alpha'-martensite are present in the deformed microstructure,
indicating the simultaneous stress-induced and strain-induced transformations of
the austenite. The effects of a laser surface treatment and the consequent
appearance of a non-magnetic phase due to the alpha' -> gamma transformation were
investigated. The EDS maps show a high concentration of nitrogen in the
alternating hard surface layers of gammaN and alpha'N (expanded austenite and
martensite), but no significantly higher concentration of chromium or iron was
detected. The high surface hardness of this nitride layer will lead to steels and
encoders with better wear and corrosion resistance.
PMID- 27492861
TI - Negative control of TRAIL-R1 signaling by transforming growth factor beta1 in
pancreatic tumor cells involves Smad-dependent down regulation of TRAIL-R1.
AB - Pancreatic ductal adenocarcinoma (PDAC) is characterized by both, overexpression
of transforming growth factor (TGF)beta and resistance of the tumor cells to many
apoptosis-inducing stimuli. The latter negatively impacts the outcome of
therapeutic efforts and represents one important mechanism which tumor cells
utilize to escape the immune surveillance. Since TGFbeta acts as a tumor promoter
in advanced tumor stages and suppression of apoptosis is a known driver of tumor
progression, it is possible that TGFbeta functions as a crucial determinant of
tumor cell sensitivity to apoptosis in PDAC. Here, we have studied the impact of
TGFbeta on TNF-related apoptosis inducing ligand (TRAIL)-induced signaling in
PDAC cells. In TGFbeta-responsive Panc1 and Colo357 cells, TGFbeta1 reduced total
and plasma membrane-associated levels of TRAIL-R1 but not those of TRAIL-R2.
Consistent with the known predominant role of TRAIL-R1 in TRAIL-mediated
signaling in PDAC, TGFbeta1 inhibited TRAIL-induced DISC formation and apoptosis
as well as phosphorylation of MAPKs and IkappaBalpha. Similarly, it also reduced
signaling of TRAIL-R1 following its specific activation with an agonistic
antibody. In contrast, specific TRAIL-R2 signaling remained unchanged. The
TGFbeta1 effect on TRAIL-R1 expression was mimicked by ectopic expression of a
kinase-active version of the TGFbeta type I receptor ALK5 (ALK5-T204D) but not by
ALK5 double mutant lacking the ability to phosphorylate Smad proteins (RImL45
T204D). Moreover, TGFbeta regulation of TRAIL-R1 was absent in two PDAC cell
lines lacking the Smad4 gene DPC4 and siRNA-mediated silencing of Smad4 in Smad4
positive Panc1 cells abolished the TGFbeta-mediated decrease in TRAIL-R1
expression, together showing that ALK5/Smad4 signaling is crucial for TGFbeta
regulation of TRAIL-R1 expression. Our results suggest a novel tumor-promoting
function of TGFbeta1. By downregulating TRAIL-R1, TGFbeta1 may not only promote
tumor escape from immune surveillance but also negatively impact on TRAIL- or
TRAIL-R1-based therapy regimens for treatment of PDAC.
PMID- 27492863
TI - Maternal lead exposure decreases the levels of brain development and cognition
related proteins with concomitant upsurges of oxidative stress, inflammatory
response and apoptosis in the offspring rats.
AB - The presence of lead (Pb) in fetal brain may affect brain development-related
proteins. We studied whether gestational/lactational Pb-exposure affects
oxidative stress, proinflammatory response, apoptosis and levels of brain
development/cognition-related proteins, including presynaptic synaptosome
associated protein-25 (SNAP-25), postsynaptic density protein-95 (PSD-95), brain
derived neurotropic factor (BDNF), tyrosine receptor-kinase protein B (TrkB) and
vesicular acetylcholine transporter (VAChT) in the offspring. Female Wistar rats
were randomly divided into control and Pb-exposed mother groups. The Pb-exposed
rats received 0.1% (w/v) Pb acetate via drinking water during pregnancy and
lactation. Milk and mammary glands were collected from lactating mothers to
measure milk/mammary gland levels of lipid peroxide (LPO), as indicator of
oxidative stress and proinflammatory TNF-alpha. Afterwards, the pups were
sacrificed to determine brain levels of Pb, LPO, TNF-alpha, cytochrome C, SNAP
25, PSD-95, BDNF, TrkB and VAChT. The levels of LPO and TNF-alpha increased in
the milk/mammary glands of the Pb-exposed mothers, concurrently with increases in
the levels of Pb, LPO, TNF-alpha and cytochrome C and decreases in the levels of
SNAP-25, PSD-95, BDNF, TrkB and VAChT in the brains of their offspring. Our
results demonstrate that Pb-exposure during development reduces the brain levels
of PSD-95 and SNAP-25 (synaptogenesis-markers), with concomitant upsurges of
oxidative stress, TNF-alpha and apoptosis in the offspring. Furthermore, BDNF
TrkB proteins that comprehend memory-related brain cognitions and/or VAChT that
comprises cholinergic-neuromotor activities might be impaired by Pb-exposure.
These findings provide evidence of toxic effects of Pb on brain development, at
least, partially by decreasing the levels of PSD-95, SNAP-25 and other cognition
related proteins.
PMID- 27492864
TI - Electron-hole doping asymmetry of Fermi surface reconstructed in a simple Mott
insulator.
AB - It is widely recognized that the effect of doping into a Mott insulator is
complicated and unpredictable, as can be seen by examining the Hall coefficient
in high Tc cuprates. The doping effect, including the electron-hole doping
asymmetry, may be more straightforward in doped organic Mott insulators owing to
their simple electronic structures. Here we investigate the doping asymmetry of
an organic Mott insulator by carrying out electric-double-layer transistor
measurements and using cluster perturbation theory. The calculations predict that
strongly anisotropic suppression of the spectral weight results in the Fermi arc
state under hole doping, while a relatively uniform spectral weight results in
the emergence of a non-interacting-like Fermi surface (FS) in the electron-doped
state. In accordance with the calculations, the experimentally observed Hall
coefficients and resistivity anisotropy correspond to the pocket formed by the
Fermi arcs under hole doping and to the non-interacting FS under electron doping.
PMID- 27492866
TI - Ophthalmologist who had an affair with patient avoids sanctions because of
"unique" surgical skills.
PMID- 27492865
TI - A telephone intervention to achieve differentiation in dietary intake: a
randomized trial in paediatric primary care.
AB - BACKGROUND: Telehealth offers opportunities to extend clinical and research
interventions for paediatric obesity. OBJECTIVES: To assess utility of a
telephone intervention, implemented through a national primary care paediatric
research network, for promoting differentiation in dietary intake, consistent
with either a low-glycemic load (Low GL) or Low Fat prescription, among
overweight/obese school-age children. METHODS: Five-week telephone dietary
counselling intervention for parents of overweight/obese school-age children
recruited through the Slone Center Office-based Research Network. Parent-child
dyads were randomized to Low GL or Low Fat diet. Primary outcomes were dietary GL
and dietary fat, adjusted for energy intake and assessed by 24-h dietary recall.
RESULTS: Subjects were randomized to Low GL (n = 11, 8.1 +/- 1.7 years, 45.5%
male) or Low Fat (n = 11, 8.2 +/- 2.0 years, 36.4% male), with no baseline
differences. Overall, 86% of subjects attended at least four of five counselling
sessions, and study completion rate was 91% (based on completion of the final
dietary recalls). Reported satisfaction was high. In adjusted analyses limited to
'recall completers,' reduction in dietary GL (g/1000 kcal) achieved within the
Low GL group was significant (p = 0.01) and greater than the change in dietary GL
in the Low Fat group (mean +/- SE; -12.9 +/- 4.4 vs. 5.1 +/- 4.9, p = 0.03).
Similarly, reduction in dietary fat (% of total energy) within the Low Fat group
was significant (-5.6 +/- 2.5, p = 0.046) but with no difference between groups
(p = 0.25). CONCLUSION: A telephone-based dietary intervention for
overweight/obese children, implemented through a national paediatric research
network, fostered prescribed dietary changes. ClinicalTrials.gov registration:
NCT00620152.
PMID- 27492867
TI - Bariatric Radioembolization: A Pilot Study on Technical Feasibility and Safety in
a Porcine Model.
AB - PURPOSE: To evaluate feasibility of left gastric artery (LGA) yttrium-90 ((90)Y)
radioembolization as potential treatment for obesity in a porcine model.
MATERIALS AND METHODS: This study included 8 young female pigs (12-13 weeks, 21.8
28.1 kg). Six animals received infusions of (90)Y resin microspheres (46.3-105.1
MBq) into the main LGA and the gastric artery arising from the splenic artery.
Animal weight and serum ghrelin were measured before treatment and weekly
thereafter. Animals were euthanized 69-74 days after treatment, and histologic
analyses of mucosal integrity and ghrelin immunoreactive cell density were
performed. RESULTS: Superficial mucosal ulcerations < 3.0 cm(2) were noted in 5
of 6 treated animals. Ghrelin immunoreactive cell density was significantly lower
in treated versus untreated animals in the stomach fundus (13.5 vs 34.8, P < .05)
and stomach body (11.2 vs 19.8, P < .05). Treated animals gained less weight than
untreated animals over the study duration (40.2 kg +/- 5.4 vs 54.7 kg +/- 6.5, P
= .053). Average fundic parietal area (165 cm(2) vs 282 cm(2), P = .067) and
average stomach weight (297.2 g vs 397.0 g, P = .067) were decreased in treated
versus untreated animals. Trichrome staining revealed significantly more fibrosis
in treatment animals compared with control animals (13.0 vs 8.6, P < .05). No
significant differences were identified in plasma ghrelin concentrations (P =
.24). CONCLUSIONS: LGA (90)Y radioembolization is promising as a potential
treatment for obesity. A larger preclinical study is needed to evaluate the
safety and efficacy of this procedure further.
PMID- 27492868
TI - Multicentric Reticulohistiocytosis in a 5-Year-Old Girl.
PMID- 27492869
TI - Unintentional Injuries in Children Up to Six Years of Age and Related Parental
Knowledge, Attitudes, and Behaviors in Italy.
AB - OBJECTIVES: To describe risk factors associated with unintentional injuries among
children aged <6 years and to examine parents' level of knowledge, attitudes, and
behaviors about pediatric injuries and related preventive measures. STUDY DESIGN:
A cross-sectional survey was conducted between May and July 2015 on a random
sample of 794 parents of 3- to 6-year-old children through a self-administered
anonymous questionnaire. RESULTS: A total of 409 parents participated. Two-thirds
of the children had experienced at least 1 unintentional injury in the previous
12 months. More than one-half of these children were boys. The leading cause was
falls; the injuries occurred mainly at home, and only 9.2% were brought for
attention to an emergency department. Parents who did not believe that it is
possible to prevent unintentional injuries were more likely to have had a child
injured. Approximately 70% of respondents were aware of security measures to
prevent pediatric injuries, and this knowledge was more prevalent in older
parents and in those with at least a college level of education compared with
those with a middle school education. The perceived utility of education about
preventive measures of pediatric injuries had a mean value of 8.9 on a Likert
scale of 1-10 (1, not useful, to 10, very useful) and was significantly higher in
mothers. CONCLUSIONS: This study highlights a clear need for public health
educational programs for parents regarding prevention of unintentional injuries
in children as a valuable tool to increase safety and injury prevention and to
reduce risks, because the majority of such injuries occur at home.
PMID- 27492870
TI - Pressure-Flow Analysis for the Assessment of Pediatric Oropharyngeal Dysphagia.
AB - OBJECTIVES: To determine which objective pressure-impedance measures of
pharyngeal swallowing function correlated with clinically assessed severity of
oropharyngeal dysphagia (OPD) symptoms. STUDY DESIGN: Forty-five children with
OPD and 34 control children without OPD were recruited and up to 5 liquid bolus
swallows were recorded with a solid-state high-resolution manometry with
impedance catheter. Individual measures of pharyngeal and upper esophageal
sphincter (UES) function and a swallow risk index composite score were derived
for each swallow, and averaged data for patients with OPD were compared with
those of control children without OPD. Clinical severity of OPD symptoms and oral
feeding competency was based on the validated Dysphagia Disorders Survey and
Functional Oral Intake Scale. RESULTS: Those objective measures that were markers
of UES relaxation, UES opening, and pharyngeal flow resistance differentiated
patients with and without OPD symptoms. Patients demonstrating abnormally high
pharyngeal intrabolus pressures and high UES resistance, markers of outflow
obstruction, were most likely to have signs and symptoms of overt Dysphagia
Disorders Survey (OR 9.24, P = .05, and 9.7, P = .016, respectively). CONCLUSION:
Pharyngeal motor patterns can be recorded in children by the use of HRIM and
pharyngeal function can be defined objectively with the use of pressure-impedance
measures. Objective measurements suggest that pharyngeal dysfunction is common in
children with clinical signs of OPD. A key finding of this study was evidence of
markers of restricted UES opening.
PMID- 27492871
TI - A cold plasma jet accelerates wound healing in a murine model of full-thickness
skin wounds.
AB - Cold plasma has been successfully applied in several fields of medicine that
require, for example, pathogen inactivation, implant functionalization or
alteration of cellular activity. Previous studies have provided evidence that
plasma supports the healing of wounds owing to its beneficial mixtures of
reactive species and modulation of inflammation in cells and tissues. To
investigate the wound healing activity of an atmospheric pressure plasma jet in
vivo, we examined the cold plasma's efficacy on dermal regeneration in a murine
model of dermal full-thickness ear wound. Over 14 days, female mice received
daily plasma treatment. Quantitative analysis by transmitted light microscopy
demonstrated a significantly accelerated wound re-epithelialization at days 3-9
in comparison with untreated controls. In vitro, cold plasma altered keratinocyte
and fibroblast migration, while both cell types showed significant stimulation
resulting in accelerated closure of gaps in scratch assays. This plasma effect
correlated with the downregulation of the gap junctional protein connexin 43
which is thought to be important in the regulation of wound healing. In addition,
plasma induced profound changes in adherence junctions and cytoskeletal dynamics
as shown by downregulation of E-cadherin and several integrins as well as actin
reorganization. Our results theorize cold plasma to be a beneficial treatment
option supplementing existing wound therapies.
PMID- 27492873
TI - Suicide Risk Among Wounded U.S. Service Members.
AB - The association between suicide and combat injuries sustained during the wars in
Iraq and Afghanistan was examined. A retrospective population-based cohort design
was conducted using official military records to identify combat injuries
(October 7, 2001, to December 31, 2007). Those who were injured during combat had
higher crude suicide rates than those who deployed and were not injured
(incidence rate ratio [IRR] = 1.50; confidence interval [CI] = 1.06, 2.12), or
never deployed (IRR = 1.46; CI = 1.04, 2.06). After adjusting for demographics,
these findings were no longer statistically significant. Although our data did
not support an elevated suicide risk among wounded service members, additional
research is needed to examine the impact of injury severity.
PMID- 27492874
TI - An optimised multi-host trematode life cycle: fishery discards enhance trophic
parasite transmission to scavenging birds.
AB - Overlapping distributions of hosts and parasites are critical for successful
completion of multi-host parasite life cycles and even small environmental
changes can impact on the parasite's presence in a host or habitat. The
generalist Cardiocephaloides longicollis was used as a model for multi-host
trematode life cycles in marine habitats. This parasite was studied to quantify
parasite dispersion and transmission dynamics, effects of biological changes and
anthropogenic impacts on life cycle completion. We compiled the largest host
dataset to date, by analysing 3351 molluscs (24 species), 2108 fish (25 species)
and 154 birds (17 species) and analysed the resultant data based on a number of
statistical models. We uncovered extremely low host specificity at the second
intermediate host level and a preference of the free-swimming larvae for
predominantly demersal but also benthic fish. The accumulation of encysted larvae
in the brain with increasing fish size demonstrates that parasite numbers level
off in fish larger than 140mm, consistent with parasite-induced mortality at
these levels. The highest infection rates were detected in host species and sizes
representing the largest fraction of Mediterranean fishery discards (up to 67% of
the total catch), which are frequently consumed by seabirds. Significantly higher
parasite densities were found in areas with extensive fishing activity than in
those with medium and low activity, and in fish from shallow lagoons than in fish
from other coastal areas. For the first time, C. longicollis was also detected in
farmed fish in netpens. Fishing generally drives declines in parasite abundance,
however, our study suggests an enhanced transmission of generalist parasites such
as C. longicollis, an effect that is further amplified by the parasite's
efficient host-finding mechanisms and its alteration of fish host behaviour by
larvae encysted in the brain. The anthropogenic impact on the distribution of
trophically-transmitted, highly prevalent parasites likely results in a strong
effect on food web structure, thus making C. longicollis an ideal bioindicator to
compare food webs in natural communities versus those impacted by fisheries and
aquaculture.
PMID- 27492875
TI - Tracking adenovirus genomes identifies morphologically distinct late DNA
replication compartments.
AB - In adenoviral virions, the genome is organized into a chromatin-like structure by
viral basic core proteins. Consequently viral DNAs must be replicated,
chromatinized and packed into progeny virions in infected cells. Although viral
DNA replication centers can be visualized by virtue of viral and cellular
factors, the spatiotemporal regulation of viral genomes during subsequent steps
remains to be elucidated. In this study, we used imaging analyses to examine the
fate of adenoviral genomes and to track newly replicated viral DNA as well as
replication-related factors. We show de novo formation of a subnuclear domain,
which we termed Virus-induced Post-Replication (ViPR) body, that emerges
concomitantly with or immediately after disintegration of initial replication
centers. Using a nucleoside analogue, we show that viral genomes continue being
synthesized in morphologically distinct replication compartments at the periphery
of ViPR bodies and are then transported inward. In addition, we identified a
nucleolar protein Mybbp1a as a molecular marker for ViPR bodies, which
specifically associated with viral core protein VII. In conclusion, our work
demonstrates the formation of previously uncharacterized viral DNA replication
compartments specific for late phases of infection that produce progeny viral
genomes accumulating in ViPR bodies.
PMID- 27492876
TI - Detecting the Collapse of Cooperation in Evolving Networks.
AB - The sustainability of biological, social, economic and ecological communities is
often determined by the outcome of social conflicts between cooperative and
selfish individuals (cheaters). Cheaters avoid the cost of contributing to the
community and can occasionally spread in the population leading to the complete
collapse of cooperation. Although such collapse often unfolds unexpectedly, it is
unclear whether one can detect the risk of cheater's invasions and loss of
cooperation in an evolving community. Here, we combine dynamical networks and
evolutionary game theory to study the abrupt loss of cooperation with tools for
studying critical transitions. We estimate the risk of cooperation collapse
following the introduction of a single cheater under gradually changing
conditions. We observe an increase in the average time it takes for cheaters to
be eliminated from the community as the risk of collapse increases. We argue that
such slow system response resembles slowing down in recovery rates prior to a
critical transition. In addition, we show how changes in community structure
reflect the risk of cooperation collapse. We find that these changes strongly
depend on the mechanism that governs how cheaters evolve in the community. Our
results highlight novel directions for detecting abrupt transitions in evolving
networks.
PMID- 27492877
TI - Oxidation of municipal wastewater by free radicals mechanism. A UV/Vis
spectroscopy study.
AB - This study investigates the oxidation of municipal wastewater (WW) by
complexation with natural polyphenols having radical scavenging activity, such as
(3,4,5 tri-hydroxy-benzoic acid) gallic acid (GA) in alkaline pH (>7), under
ambient O2 and temperature. Physicochemical and structural characteristics of GA
WW complex-forming are evaluated by UV/Vis spectroscopy. The comparative analysis
among UV/Vis spectra of GA monomer, GA-GA polymer, WW compounds, and GA-WW
complex reveals significant differences within 350-450 and 500-900 nm. According
to attenuated total reflectance (ATR) spectroscopy and thermogravimetric analysis
(TGA), these spectra differences correspond to distinct complexes formed. This
study suggests a novel role of natural polyphenols on the degradation and
humification of wastes.
PMID- 27492878
TI - Joint damage and motor learning during unipedal stance in haemophilia
arthropathy: report of two cases.
PMID- 27492879
TI - Tunable dual emission in visible and near-infrared spectra using Co(2+)-doped
PbSe nanocrystals embedded in a chalcogenide glass matrix.
AB - Semimagnetic Pb1-xCoxSe nanocrystals were synthesized by a fusion protocol in a
glass matrix and characterized by optical absorption (OA), transmission electron
microscopy (TEM), and photoluminescence (PL) techniques. OA spectra and TEM
images strongly indicated the formation of Pb1-xCoxSe magnetic phases in the
glass system and the quantum dot size was manipulated by tuning the annealing
time. The OA spectra together with crystal field theory indicate that Co(2+) is
located in the tetrahedral site (Td) and the PL of the Pb1-xCoxSe nanocrystals
presents characteristic recombination in the visible (~700 nm) and near-IR (1300
1600 nm) electromagnetic spectral range. With temperature decreasing, the PL
spectra, in the visible spectral range, indicate an excited-state crossover
yielding PL changes from (4)T1(P) -> (4)A2(F) broadband emission to (2)E(G) ->
(4)A2(F) narrow-line emission. This phenomenon was explained on the basis of a
configurational energy model. The OA and PL spectra of PbSe:Co(2+) indicate that
the localized energy transition of Co(2+) ((4)A2(F) <-> (4)T1((4)F)) can be tuned
from the band-gap energy to the conduction-band energy of PbSe NCs by changing
the NC size by increasing the thermal annealing time. In the near-IR spectral
range, the temperature-dependent PL spectra show that the process of thermal
activation of localized electrons in Co(2+) states can be transferred to the
conduction band of the NCs. This process depends on the energy distance between
extended and localized states, which can be controlled by the sample annealing
time.
PMID- 27492880
TI - Depression Screening Using Daily Mental-Health Ratings from a Smartphone
Application for Breast Cancer Patients.
AB - BACKGROUND: Mobile mental-health trackers are mobile phone apps that gather self
reported mental-health ratings from users. They have received great attention
from clinicians as tools to screen for depression in individual patients. While
several apps that ask simple questions using face emoticons have been developed,
there has been no study examining the validity of their screening performance.
OBJECTIVE: In this study, we (1) evaluate the potential of a mobile mental-health
tracker that uses three daily mental-health ratings (sleep satisfaction, mood,
and anxiety) as indicators for depression, (2) discuss three approaches to data
processing (ratio, average, and frequency) for generating indicator variables,
and (3) examine the impact of adherence on reporting using a mobile mental-health
tracker and accuracy in depression screening. METHODS: We analyzed 5792 sets of
daily mental-health ratings collected from 78 breast cancer patients over a 48
week period. Using the Patient Health Questionnaire-9 (PHQ-9) as the measure of
true depression status, we conducted a random-effect logistic panel regression
and receiver operating characteristic (ROC) analysis to evaluate the screening
performance of the mobile mental-health tracker. In addition, we classified
patients into two subgroups based on their adherence level (higher adherence and
lower adherence) using a k-means clustering algorithm and compared the screening
accuracy between the two groups. RESULTS: With the ratio approach, the area under
the ROC curve (AUC) is 0.8012, indicating that the performance of depression
screening using daily mental-health ratings gathered via mobile mental-health
trackers is comparable to the results of PHQ-9 tests. Also, the AUC is
significantly higher (P=.002) for the higher adherence group (AUC=0.8524) than
for the lower adherence group (AUC=0.7234). This result shows that adherence to
self-reporting is associated with a higher accuracy of depression screening.
CONCLUSIONS: Our results support the potential of a mobile mental-health tracker
as a tool for screening for depression in practice. Also, this study provides
clinicians with a guideline for generating indicator variables from daily mental
health ratings. Furthermore, our results provide empirical evidence for the
critical role of adherence to self-reporting, which represents crucial
information for both doctors and patients.
PMID- 27492881
TI - Effect of regional versus local anaesthesia on outcome after arteriovenous
fistula creation: a randomised controlled trial.
AB - BACKGROUND: Arteriovenous fistulae are the optimum form of vascular access in end
stage renal failure. However, they have a high early failure rate. Regional
compared with local anaesthesia results in greater vasodilatation and increases
short-term blood flow. This study investigated whether regional compared with
local anaesthesia improved medium-term arteriovenous fistula patency. METHODS:
This observer-blinded, randomised controlled trial was done at three university
hospitals in Glasgow, UK. Adults undergoing primary radiocephalic or
brachiocephalic arteriovenous fistula creation were randomly assigned (1:1; in
blocks of eight) using a computer-generated allocation system to receive either
local anaesthesia (0.5% L-bupivacaine and 1% lidocaine injected subcutaneously)
or regional (brachial plexus block [BPB]) anaesthesia (0.5% L-bupivacaine and
1.5% lidocaine with epinephrine). Patients were excluded if they were
coagulopathic, had no suitable vessels, or had a previous failed ipsilateral
fistula. The primary endpoint was arteriovenous fistula patency at 3 months. We
analysed the data on an intention-to-treat basis. This study was registered with
ClinicalTrials.gov (NCT01706354) and is complete. FINDINGS: Between Feb 6, 2013,
and Dec 4, 2015, 163 patients were assessed for eligibility and 126 patients were
randomly assigned to local anaesthesia (n=63) or BPB (n=63). All patients
completed follow-up on an intention-to-treat basis. Primary patency at 3 months
was higher in the BPB group than the local anaesthesia group (53 [84%] of 63
patients vs 39 [62%] of 63; odds ratio [OR] 3.3 [95% CI 1.4-7.6], p=0.005) and
was greater in radiocephalic fistulae (20 [77%] of 26 patients vs 12 [48%] of 25;
OR 3.6 [1.4-3.6], p=0.03). There were no significant adverse events related to
the procedure. INTERPRETATION: Compared with local anaesthesia, BPB significantly
improved 3 month primary patency rates for arteriovenous fistulae. FUNDING:
Regional Anaesthesia UK, Darlinda's Charity for Renal Research.
PMID- 27492882
TI - Improving outcomes in dialysis fistulae.
PMID- 27492883
TI - Observations of oral hygiene care interventions provided by nurses to
hospitalized older people.
AB - Dependent older hospitalized patients rely on nurses to assist them with the
removal of plaque from their teeth, dentures, and oral cavities. Oral care
interventions by 25 nurses on post-acute units, where patients have longer
hospital stays, were observed during evening care. In addition to efforts to
engage patients in oral care, nurses provided the following interventions: (a)
supporting the care of persons with dentures; (b) supporting the care of natural
teeth; (c) cleansing the tongue and oral cavity; and (d) moisturizing lips and
oral tissues. Patients' oral hygiene care was supported in just over one-third of
encounters. Denture care was inconsistently performed, and was infrequently
followed by care of the oral cavity. Nurses did not encourage adequate self-care
of natural teeth by patients, and infrequently moisturized tissues. Evidence
based oral hygiene care standards are required to assist nurses to support
patients in achieving optimal oral hygiene outcomes.
PMID- 27492884
TI - Are nursing home care workers' health and presenteeism associated with implicit
rationing of care? A cross-sectional multi-site study.
AB - To explore associations between care workers' health and implicit rationing of
care. Diverse studies have linked impaired health to reduced work performance - a
factor measured through omission of required tasks. This cross-sectional study
gathered data from 3239 care workers in 162 Swiss nursing homes. Data were
analyzed via a linear logistic regression model using general estimating
equations. Overall, rationing of care occurred "never" to "seldom." Rationing of
activities of daily living was positively associated with care workers' joint
pain (beta 0.04, CI 0.001-0.07), emotional exhaustion (beta 0.11, CI 0.07-0.15),
and presenteeism (beta 0.05, CI 0.004-0.09). Rationing of caring, rehabilitation,
and monitoring was positively associated with care workers' joint pain (beta
0.05, CI 0.01-0.09) and emotional exhaustion (beta 0.2, CI 1.16-0.24). Care
workers health complaints are strongly associated with rationing of tasks
directly related to resident care.
PMID- 27492885
TI - Genetic evidence for a role of the SREBP transcription system and lipid
biosynthesis in schizophrenia and antipsychotic treatment.
AB - Schizophrenia is a serious psychotic disorder, with disabling symptoms and
markedly reduced life expectancy. The onset is usually in late adolescence or
early adulthood, which in time overlaps with the maturation of the brain
including the myelination process. Interestingly, there seems to be a link
between myelin abnormalities and schizophrenia. The oligodendrocyte-derived
myelin membranes in the CNS are highly enriched for lipids (cholesterol,
phospholipids and glycosphingolipids), thereby pointing at lipid homeostasis as a
relevant target for studying the genetics and pathophysiology of schizophrenia.
The biosynthesis of fatty acids and cholesterol is regulated by the sterol
regulatory element binding protein (SREBP) transcription factors SREBP1 and
SREBP2, which are encoded by the SREBF1 and SREBF2 genes on chromosome 17p11.2
and 22q13.2, respectively. Here we review the evidence for the involvement of
SREBF1 and SREBF2 as genetic risk factors in schizophrenia and discuss the role
of myelination and SREBP-mediated lipid biosynthesis in the etiology,
pathophysiology and drug treatment of schizophrenia.
PMID- 27492886
TI - Traumatic stress causes distinctive effects on fear circuit catecholamines and
the fear extinction profile in a rodent model of posttraumatic stress disorder.
AB - Central catecholamines regulate fear memory across the medial prefrontal cortex
(mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence
exists to address the relationships among these fear circuit areas in terms of
the fear symptoms of posttraumatic stress disorder (PTSD). By examining the
behavioral profile in a Pavlovian fear conditioning paradigm together with
tissue/efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake
abilities across the fear circuit areas in rats that experienced single prolonged
stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired
extinction retrieval was concomitant with the changes of central DA/NE in a
dissociable manner. For tissue levels, diminished DA and increased NE were both
observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were
consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the
infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a
lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC
after SPS. Finally, negative correlations were observed between retrieval
freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid
after SPS. Our results suggest that central catecholamines are crucially involved
in the retrieval of fear extinction in which DA and NE play distinctive roles
across the fear circuit areas.
PMID- 27492887
TI - Enantioselective isothiourea-catalysed trans-dihydropyridinone synthesis using
saccharin-derived ketimines: scope and limitations.
AB - The catalytic enantioselective synthesis of a range of trans-dihydropyridinones
from aryl-, heteroaryl- and alkenylacetic acids and saccharin-derived ketimines
with good to excellent stereocontrol (15 examples, up to >95 : 5 dr, up to >99 :
1 er) is reported. After extensive optimisation, HyperBTM proved the optimal
isothiourea catalyst for this transformation at -78 degrees C, giving trans
dihydropyridones with generally excellent levels of diastereo- and
enantioselectivity.
PMID- 27492888
TI - Establishment of an appropriate fall prevention program: A community-based study.
AB - AIM: To identify an appropriate community-based fall prevention program METHODS:
We introduced two programs to 24 senior centers, "community salons," in a
Japanese city, and carried out a prospective controlled trial between 2004 and
2005. Eight salons (185 participants aged 72.0 +/- 7.1 years) received a single
visit program consisting of one multidisciplinary team visit that included fall
risk assessment with feedback and a fall prevention lecture. A total of 16 salons
(418 participants aged 73.6 +/- 7.4 years) received a year-round comprehensive
program, with visits carried out every 3 months. We compared the fall rates for 1
year between the two programs. Based on the results, we implemented a modified
program until 2014 and examined the long-term consequences. RESULTS: In the
prospective controlled trial, fall rates did not differ significantly between
programs (P = 0.449). Instead, fall rates for both programs decreased
significantly by 0.89 (95% CI 0.84-0.94) times each month. Therefore, we
implemented a modified version of the single-visit program. By March 2014, the
programs had been delivered to 1863 individuals, and the total number of
attendees was 6622. The average attendance frequency per participant was 0.62
times per year. The majority (85.3%) of salons requested the program every year.
Overall, the risk of falling (fall rates in the preceding year) decreased
significantly as the number of program attendances increased (incident rate ratio
= 0.89, 95% CI 0.85-0.92) irrespective of initial program types. CONCLUSIONS: The
programs including fall risk assessment with feedback and a fall prevention
lecture reduced falls when embedded into the community, and they were accepted
well over the course of 10 years. Geriatr Gerontol Int 2017; 17: 1081-1089.
PMID- 27492889
TI - Composition, microstructure and element study of urinary calculi.
AB - To better understand the basis of urinary calculi formation, we studied the
composition, microstructure, and element analysis of different types of urinary
calculi. Sixty people with urinary stones in Shanxi province were selected
randomly. The composition of urinary stones was analyzed using Fourier transform
infrared spectroscopy. The microstructure of material components was observed by
a scanning electron microscopy and the elemental distribution and composition
were analyzed by an X-ray energy spectrometer. Furthermore, general information,
BMI, history of medicine, chronic medical history, family history, and recurrence
rates were collected. Female-to-male ratio was 1:2.5; median age was 43.2 years
old. Of the patients, 13.3% were found definite family history and 46.6% of
patients for recurrence history. It was found that mixed stones account for the
largest proportion (65%), followed by calcium oxalate monohydrate calculi
(26.67%). In mixed stones, the mixture of calcium oxalate monohydrate and
hydroxyapatite had the largest proportion, accounting for 71.79%. Stones showed
different microcosmic characteristics and element distribution. Stones varied
widely in distribution, infrared spectrum, microstructure, and element
composition, which provided an important basis for urinary calculi research
regarding urinary stone formation.
PMID- 27492890
TI - Thermophysical properties of imidazolium tricyanomethanide ionic liquids:
experiments and molecular simulation.
AB - The low-viscous tricyanomethanide ([TCM](-))-based ionic liquids (ILs) are
gaining increasing interest as attractive fluids for a variety of industrial
applications. The thermophysical properties (density, viscosity, surface tension,
electrical conductivity and self-diffusion coefficient) of the 1-alkyl-3
methylimidazolium tricyanomethanide [Cnmim][TCM] (n = 2, 4 and 6-8) IL series
were experimentally measured over the temperature range from 288 to 363 K.
Moreover, a classical force field optimized for the imidazolium-based [TCM](-)
ILs was used to calculate their thermodynamic, structural and transport
properties (density, surface tension, self-diffusion coefficients, viscosity) in
the temperature range from 300 to 366 K. The predictions were directly compared
against the experimental measurements. The effects of anion and alkyl chain
length on the structure and thermophysical properties have been evaluated. In
cyano-based ILs, the density decreases with increasing molar mass, in contrast to
the behavior of the fluorinated anions, being in agreement with the literature.
The contribution per -CH2- group to the increase of the viscosity presents the
following sequence: [PF6](-) > [BF4](-) > [Tf2N](-) > [DCA](-) > [TCB](-) >
[TCM](-). [TCM](-)-based ILs show lower viscosity than dicyanamide ([DCA](-))-
and tetracyanoborate ([TCB](-))-based ILs, while the latter two exhibit a
crossover which depends both on temperature and the alkyl chain length of the
cation. The surface tension of the investigated ILs decreases with increasing
alkyl chain length. [C2mim][TCM] shows an outlier behavior compared to other
members of the homologous series. The surface enthalpies and surface entropies
for all the studied systems have been calculated based on the experimentally
determined surface tensions. The relationship between molar conductivity and
viscosity was analyzed using the Walden rule. The experimentally determined self
diffusion coefficients of the cations are in good agreement with the molecular
simulation predictions, in which a decrease of the self-diffusion of the cations
with increasing alkyl chain length is observed with a simultaneous increase in
viscosity and for the longer alkyl lengths the anion becomes more mobile than the
cation.
PMID- 27492891
TI - Filaggrin gene loss-of-function variants modify the effect of breast-feeding on
eczema risk in early childhood.
PMID- 27492894
TI - A seminal molecular marker for sperm presence in non-obstructive azoospermia?
PMID- 27492893
TI - Patient and caregiver expectations of emergency department care: A scoping
literature review.
AB - BACKGROUND: Communication between health care providers (HCPs) and patients
and/or their caregivers in the chaotic emergency department (ED) context can be
challenging and potentially impact health outcomes and patient satisfaction.
Studies examining strategies to improve communication of patient and caregivers
expectations of care in an ED are widely dispersed. METHODS: We conducted a
scoping review of the published and grey literature to examine the extent, range
and nature of existing research evidence regarding strategies to enhance
communication of patient and caregiver expectations of care in an ED. RESULTS: Of
the 599 articles retrieved, 24 met the inclusion criteria. Most of the studies
identified included patients (n=9) or caregivers (n=8) as the population of
interest, while the remainder examined the expectations of a mix of patients,
parents/caregivers, and/or HCPs (n=7). The majority (n=21) of the studies did not
communicate patient/caregiver expectations to HCPs. CONCLUSION: This scoping
review highlights the paucity of available research literature evaluating
strategies to communicate patient and caregiver ED expectations. Our findings
identify the need for experimental designs in future studies to evaluate
implementation strategies for ED expectation tools with a particular emphasis on
measuring the impact of sharing patient expectations with HCPs.
PMID- 27492892
TI - Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer
patients: Discovery and validation studies.
AB - Current screening methods for ovarian cancer can only detect advanced disease.
Earlier detection has proved difficult because the molecular precursors involved
in the natural history of the disease are unknown. To identify early driver
mutations in ovarian cancer cells, we used dense whole genome sequencing of
micrometastases and microscopic residual disease collected at three time points
over three years from a single patient during treatment for high-grade serous
ovarian cancer (HGSOC). The functional and clinical significance of the
identified mutations was examined using a combination of population-based whole
genome sequencing, targeted deep sequencing, multi-center analysis of protein
expression, loss of function experiments in an in-vivo reporter assay and
mammalian models, and gain of function experiments in primary cultured fallopian
tube epithelial (FTE) cells. We identified frequent mutations involving a 40kb
distal repressor region for the key stem cell differentiation gene SOX2. In the
apparently normal FTE, the region was also mutated. This was associated with a
profound increase in SOX2 expression (p<2(-16)), which was not found in patients
without cancer (n=108). Importantly, we show that SOX2 overexpression in FTE is
nearly ubiquitous in patients with HGSOCs (n=100), and common in BRCA1-BRCA2
mutation carriers (n=71) who underwent prophylactic salpingo-oophorectomy. We
propose that the finding of SOX2 overexpression in FTE could be exploited to
develop biomarkers for detecting disease at a premalignant stage, which would
reduce mortality from this devastating disease.
PMID- 27492896
TI - Socioeconomic Status in Relation to the Risk of Ovarian Cancer in African
American Women: A Population-Based Case-Control Study.
AB - We investigated the association between socioeconomic status and ovarian cancer
in African-American women. We used a population-based case-control study design
that included case patients with incident ovarian cancer (n = 513) and age- and
area-matched control participants (n = 721) from 10 states who were recruited
into the African American Cancer Epidemiology Study from December 2010 through
December 2014. Questionnaires were administered via telephone, and study
participants responded to questions about several characteristics, including
years of education, family annual income, and risk factors for ovarian cancer.
After adjustment for established ovarian cancer risk factors, women with a
college degree or more education had an odds ratio of 0.71 (95% confidence
interval (CI): 0.51, 0.99) when compared with those with a high school diploma or
less (P for trend = 0.02); women with family annual incomes of $75,000 or more
had an odds ratio of 0.74 (95% CI: 0.47, 1.16) when compared with those with
incomes less than $10,000 (P for trend = 0.055). When these variables were
dichotomized, compared with women with a high school diploma or less, women with
more education had an adjusted odds ratio of 0.72 (95% CI: 0.55, 0.93), and
compared with women with an income less than $25,000, women with higher incomes
had an adjusted odds ratio of 0.86 (95% CI: 0.66, 1.12). These findings suggest
that ovarian cancer risk may be inversely associated with socioeconomic status
among African-American women and highlight the need for additional evidence to
more thoroughly characterize the association between socioeconomic status and
ovarian cancer.
PMID- 27492895
TI - Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia
International Consortium.
AB - The association between tobacco smoke and acute myeloid leukemia (AML) is well
established in adults but not in children. Individual-level data on parental
cigarette smoking were obtained from 12 case-control studies from the Childhood
Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases
diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of
CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall,
maternal smoking before, during, or after pregnancy was not associated with
childhood AML; there was a suggestion, however, that smoking during pregnancy was
associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence
interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds
ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95%
CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased
risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P <
0.05), with higher risks reported for heavy smokers. Associations with paternal
smoking varied by histological type. Our analyses suggest an association between
paternal smoking and childhood AML. The association with maternal smoking appears
limited to Hispanic children, raising questions about ethnic differences in
tobacco-related exposures and biological mechanisms, as well as study-specific
biases.
PMID- 27492898
TI - Antibody-drug conjugates: Current status and future perspectives.
AB - Conventional cytotoxic agents used for the pharmacotherapy of cancer do not
selectively localize at the tumor site, which may prevent dose escalation to
therapeutically active regimens and may lead to undesired side effects and
toxicity to normal organs. There has been a growing interest in the use of
monoclonal antibodies as vehicles for the pharmacodelivery of potent cytotoxic
drugs to neoplastic lesions. This novel class of targeted biopharmaceutical
agents has the potential of improving activity and selectivity of cytotoxic
agents. However, many technical aspects contribute to the success or failure of
antibody-drug conjugates (ADCs). In this review, we summarize important pre
clinical and clinical examples of early and current improvements in the field
ADCs, including diversification of payloads, linkers, conjugation technologies,
ADC formats and type of targets. Combination therapies of ADCs with checkpoint
inhibitors are also discussed, in light of the exceptional expansion recorded in
the latter space over the last five years.
PMID- 27492899
TI - S100A8/A9: From basic science to clinical application.
AB - Neutrophils and monocytes belong to the first line of immune defence cells and
are recruited to sites of inflammation during infection or sterile injury. Both
cells contain huge amounts of the heterodimeric protein S100A8/A9 in their
cytoplasm. S100A8/A9 belongs to the Ca2+ binding S100 protein family and has
recently gained a lot of interest as a critical alarmin modulating the
inflammatory response after its release (extracellular S100A8/A9) from
neutrophils and monocytes. Extracellular S100A8/A9 interacts with the pattern
recognition receptors Toll-like receptor 4 (TLR4) and Receptor for Advanced
Glycation Endproducts (RAGE) promoting cell activation and recruitment. Besides
its biological function, S100A8/A9 (also known as myeloid related protein 8/14,
MRP8/14) was identified as interesting biomarker to monitor disease activity in
chronic inflammatory disorders including inflammatory bowel disease and
rheumatoid arthritis. Furthermore, S100A8/A9 has been tested successfully in pre
clinical imaging studies to localize sites of infection or sterile injury.
Finally, recent evidence using small molecule inhibitors for S100A8/A9 also
suggests that blocking S100A8/A9 activity exerts beneficial effects on disease
activity in animal models of autoimmune diseases including multiple sclerosis,
systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel
disease. This review will provide a comprehensive and detailed overview into the
structure and biological function of S100A8/A9 and also will give an outlook in
terms of diagnostic and therapeutic applications targeting S100A8/A9.
PMID- 27492900
TI - Platelet-vessel wall interactions and drug effects.
PMID- 27492901
TI - Primary Triage in a Mass-casualty Event Possesses a Risk of Increasing
Informational Confusion: A Simulation Study Using Shannon's Entropy.
AB - Introduction Primary triage in a mass-casualty event setting using low-visibility
tags may lead to informational confusion and difficulty in judging triage
attribution of patients. In this simulation study, informational confusion during
primary triage was investigated using a method described in a prior study that
applied Shannon's Information Theory to triage. Hypothesis Primary triage using a
low-visibility tag leads to a risk of informational confusion in prioritizing
care, owing to the intermingling of pre- and post-triage patients. It is possible
that Shannon's entropy evaluates the degree of informational confusion
quantitatively and improves primary triage. METHODS: The Simple Triage and Rapid
Treatment (START) triage method was employed. In Setting 1, entropy of a triage
area with 32 patients was calculated for the following situations: Case 1 - all
32 patients in the triage area at commencement of triage; Case 2 - 16 randomly
imported patients to join 16 post-triage patients; Case 3 - eight patients
imported randomly and another eight grouped separately; Case 4 - 16 patients
grouped separately; Case 5 - random placement of all 32 post-triage patients;
Case 6 - isolation of eight patients of minor priority level; Case 7 - division
of all patients into two groups of 16; and Case 8 - separation of all patients
into four categories of eight each. In Setting 2, entropies in the triage area
with 32 patients were calculated continuously with each increase of four post
triage patients in Systems A and B (System A - triage conducted in random manner;
and System B - triage arranged into four categories). RESULTS: In Setting 1,
entropies in Cases 1-8 were 2.00, 3.00, 2.69, 2.00, 2.00, 1.19, 1.00, and 0.00
bits/symbol, respectively. Entropy increased with random triage. In Setting 2,
entropies of System A maintained values the same as, or higher than, those before
initiation of triage: 2.00 bits/symbol throughout the triage. The graphic
waveform showed a concave shape and took 3.00 bits/symbol as maximal value when
the probability of each category was 1/8, whereas the values in System B showed a
linear decrease from 2.00 to 0.00 bits/symbol. CONCLUSION: Informational
confusion in a primary triage area measured using Shannon's entropy revealed that
random triage using a low-visibility tag might increase the degree of confusion.
Methods for reducing entropy, such as enhancement of triage colors, may
contribute to minimizing informational confusion. Ajimi Y , Sasaki M , Uchida Y ,
Kaneko I , Nakahara S , Sakamoto T . Primary triage in a mass-casualty event
possesses a risk of increasing informational confusion: a simulation study using
Shannon's entropy. Prehosp Disaster Med. 2016;31(5):498-504.
PMID- 27492897
TI - Targeting the ROS-HIF-1-endothelin axis as a therapeutic approach for the
treatment of obstructive sleep apnea-related cardiovascular complications.
AB - Obstructive sleep apnea (OSA) is now recognized as an independent and important
risk factor for cardiovascular diseases such as hypertension, coronary heart
disease, heart failure and stroke. Clinical and experimental data have confirmed
that intermittent hypoxia is a major contributor to these deleterious
consequences. The repetitive occurrence of hypoxia-reoxygenation sequences
generates significant amounts of free radicals, particularly in moderate to
severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species
(ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF
1) that promotes the transcription of numerous adaptive genes some of which being
deleterious for the cardiovascular system, such as the endothelin-1 gene. This
review will focus on the involvement of the ROS-HIF-1-endothelin signaling
pathway in OSA and intermittent hypoxia and discuss current and potential
therapeutic approaches targeting this pathway to treat or prevent cardiovascular
disease in moderate to severe OSA patients.
PMID- 27492902
TI - Dectin-1-activated dendritic cells trigger potent antitumour immunity through the
induction of Th9 cells.
AB - Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering
protective antifungal Th17 responses. However, whether dectin-1 directs DCs to
prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by
dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9
cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing
capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation
of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated
DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF
kappaB signalling pathways, resulting in increased p50 and RelB nuclear
translocation and TNFSF15 and OX40L expression. Furthermore, immunization of
tumour-bearing mice with dectin-1-activated DCs induces potent antitumour
response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in
vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9
cells and antitumour immunity and may have important clinical implications.
PMID- 27492903
TI - Sex and Race/Ethnicity Differences in Implantable Cardioverter-Defibrillator
Counseling and Use Among Patients Hospitalized With Heart Failure: Findings from
the Get With The Guidelines-Heart Failure Program.
AB - BACKGROUND: Previous studies have found that women and black patients eligible
for a primary prevention implantable cardioverter-defibrillator (ICD) are less
likely than men or white patients to receive one. METHODS: We performed an
observational analysis of the Get With The Guidelines-Heart Failure Program from
January 1, 2011, to March 21, 2014. Patients admitted with heart failure and an
ejection fraction <=35% without an ICD were included. Rates of ICD counseling
among eligible patients and ICD receipt among counseled patients were examined by
sex and race/ethnicity. RESULTS: Among 21 059 patients from 236 sites, 4755
(22.6%) received predischarge ICD counseling. Women were counseled less
frequently than men (19.3% versus 24.6%, P<0.001, adjusted odds ratio [OR], 0.84;
95% confidence interval [CI], 0.78-0.91). Racial and ethnic minorities were less
likely to receive counseling than white patients (black 22.6%, Hispanic 18.6%,
other race/ethnic group 14.4% versus white 24.3%, P<0.001 for each): adjusted OR
versus white, 0.69; 95% CI, 0.63 to 0.76 for black patients; adjusted OR, 0.62;
95% CI, 0.55 to 0.70 for Hispanic patients; adjusted OR, 0.53; 95% CI, 0.43 to
0.65 for other patients. Among the 4755 counseled patients, 2977 (62.6%) received
an ICD or had one planned for placement after hospital stay. Among those
counseled, women and men were similarly likely to receive an ICD (adjusted OR,
1.13; 95% CI, 0.99-1.29). However, black (adjusted OR, 0.70; 95% CI, 0.56-0.88)
and Hispanic patients (adjusted OR, 0.68; 95% CI, 0.46-1.01) were less likely to
receive an ICD. CONCLUSIONS: Up to 4 of 5 hospitalized patients with heart
failure eligible for ICD counseling did not receive it, particularly women and
minority patients. Among counseled patients, ICD use differences by race and
ethnicity persisted.
PMID- 27492905
TI - CO2 Reduction to CO in Water: Carbon Nanotube-Gold Nanohybrid as a Selective and
Efficient Electrocatalyst.
AB - A gold-based nanostructure has been demonstrated as promising materials for the
selective electroreduction of CO2 to CO in aqueous conditions. In this work, we
present a carbon nanotube-gold nanohybrid as a selective and efficient
electrocatalyst for the reduction of CO2 in 0.5 m NaHCO3 . The hybrid material
exhibits remarkable activity with a current density of 10 mA cm(-2) at -0.55 V
versus standard hydrogen electrode with a stable CO production rate (0.52 MUmol
s(-1) ) after 4 h electrolysis. Monodispersed gold nanoparticles anchored on
carbon nanotubes through a layer-by-layer method allows very little Au loading
and thus minimization of the cost of electrode fabrication with a mass activity
up to 100 A g(-1) at -0.55 V versus reversible hydrogen electrode. It is 33 times
higher than a previous report for monodisperse Au nanoparticles (3 A g(-1) )
while ensuring selectivity (70 % faradaic yield of CO) at comparable reduction
potential.
PMID- 27492904
TI - Pregnancy and the Risk of Aortic Dissection or Rupture: A Cohort-Crossover
Analysis.
AB - BACKGROUND: Case series have described aortic dissection and rupture in
pregnancy. Few population-based data exist to support an association. METHODS: We
performed a cohort-crossover study using data on all emergency department visits
and acute care hospitalizations at nonfederal healthcare facilities in
California, Florida, and New York. We included women >=12 years of age with labor
and delivery or abortive pregnancy outcome between 2005 and 2013. Our outcome was
a composite of aortic dissection or rupture. Based on the timing of reported
aortic complications during pregnancy, we defined the period of risk as 6 months
before delivery until 3 months after delivery. We compared each patient's
likelihood of aortic complications during this period with an equivalent 270-day
period exactly 1 year later. Incidence rates and incidence rate ratios were
computed using conditional Poisson regression with robust standard errors.
RESULTS: Among 6 566 826 pregnancies in 4 933 697 women, we identified 36 cases
of aortic dissection or rupture during the pregnancy or postpartum period and 9
cases during the control period 1 year later. The rate of aortic complications
was 5.5 (95% confidence interval, 4.0-7.8) per million patients during pregnancy
and the postpartum period, in comparison with 1.4 (95% confidence interval, 0.7
2.9) per million during the equivalent period 1 year later. Pregnancy was
associated with a significantly increased risk of aortic dissection or rupture
(incidence rate ratio, 4.0; 95% confidence interval, 2.0-8.2) in comparison with
the control period 1 year later. CONCLUSIONS: The risk of aortic dissection or
rupture is elevated during pregnancy and the postpartum period.
PMID- 27492906
TI - HLA-A*23:01:19, a novel variant of HLA-A*23:01, discovered in a West African stem
cell transplantation patient.
AB - HLA-A*23:01:19 differs from HLA-A*23:01:01 by a single substitution in exon 4.
PMID- 27492907
TI - Walking Throughout Your Day Keeps Depression (and a Host of Other Health
Problems) Away.
PMID- 27492908
TI - Effects of a Sedentary Behavior-Inducing Randomized Controlled Intervention on
Depression and Mood Profile in Active Young Adults.
AB - OBJECTIVE: To examine the effects of a free-living, sedentary behavior-inducing
randomized controlled intervention on depression and mood profile. PATIENTS AND
METHODS: Participants who were confirmed to be active via self-report and
accelerometry were randomly assigned to either a sedentary behavior intervention
group (n=26) or a control group (n=13) by using a 2:1 sample size ratio for
intervention and control groups. The intervention group was asked to eliminate
all exercise and minimize steps to 5000 or less steps/d for 1 week, whereas the
control group was asked to continue normal physical activity levels for 1 week.
Both groups completed a depression (Patient Health Questionnaire-9) and mood
(Profile of Moods States) survey preintervention and immediately
postintervention. The intervention group was asked to resume normal physical
activity levels for 1 week postintervention and then completed the assessments
for a third time. All data collection occurred between September 1, 2015, and
December 1, 2015. RESULTS: Patient Health Questionnaire-9 group * time
interaction analysis revealed that depression scores significantly increased from
visit 1 to visit 2 (F=11.85; P=.001). Paired t tests comparing depression scores
from visit 2 to visit 3 exhibited a significant decrease from visit 2 to visit 3
(P<.001). Profile of Moods States group * time interaction analysis paralleled
depression results; mood scores significantly increased from visit 1 to visit 2
(F=10.03; P=.003) and significantly decreased from visit 2 to visit 3 (P<.001).
CONCLUSION: A 1-week sedentary behavior-inducing intervention has deleterious
effects on depression and mood. To prevent mental health decline in active
individuals, consistent regular physical activity may be necessary.
PMID- 27492909
TI - Physical Activity and Alzheimer Disease: A Protective Association.
AB - OBJECTIVE: To explore whether being physically active can decrease Alzheimer
disease (AD) risk. PARTICIPANTS AND METHODS: We conducted a meta-analysis of
prospective observational cohort studies reporting the association between
physical activity (PA) and incident AD. Relevant articles were identified by
title and abstract in the electronic databases PubMed, ScienceDirect, and Scopus
using the keywords Alzheimer, Alzheimer disease, Alzheimer's, Alzheimer's
disease, physical activity, sport, exercise, sedentary, fitness, and combinations
thereof for articles published in any language up to February 15, 2016. Criteria
for consideration included division of the study cohort by PA levels and sample
size specification for each PA level group, quantification (number) of persons
who had development of AD, and PA assessment during time off work (not just work
time). We followed the MOOSE (Meta-analyses of Observational Studies in
Epidemiology) recommendations and used the Newcastle-Ottawa scale for study
quality assessment. RESULTS: Ten high-quality studies were included in meta
analysis I (23,345 participants). Follow-up ranged from 3.9 to 31 years, and the
participants' age ranged from 70 to 80 years. The pooled odds ratio for
development of AD in participants who were more vs less physically active was
0.65 (95% CI, 0.56-0.74; P<.001; no publication bias [P=.24] but with
heterogeneity among studies [I(2)=31.32%]). We could identify participants'
adherence to international PA recommendations in 5 studies, which constituted
meta-analysis II (10,615 participants). The pooled odds ratio for development of
AD in participants who were active vs those who were inactive was 0.60 (95% CI,
0.51-0.71; P<.001; no publication bias [P=.34] and no heterogeneity
[I(2)=5.63%]). CONCLUSION: Although the limitations of self-reported PA data must
be considered, regular PA performed by elderly people might play a certain
protective role against AD.
PMID- 27492910
TI - Effect of Preprocedural Thrombocytopenia on Prognosis After Percutaneous Coronary
Intervention.
AB - OBJECTIVE: To assess early and late outcomes, including bleeding, in patients
with thrombocytopenia undergoing percutaneous coronary intervention (PCI).
PATIENTS AND METHODS: We performed a retrospective single-center study of
patients with preprocedural thrombocytopenia (platelet count <=100,000/MUL;
n=204) undergoing PCI between 2003 and 2015. Inhospital and late outcomes were
compared with those of a matched control group without thrombocytopenia (n=1281).
RESULTS: The most common causes of thrombocytopenia were liver disease, immune
mediated disease, and hematologic malignant neoplasms. Inhospital bleeding events
after PCI were similar in patients with thrombocytopenia and matched controls (24
of 146 [16.4%] vs 179 of 1281 [14.0%]; P=.40) and were largely classified as
minor using the Bleeding Academic Research Consortium (BARC) classification (89%
BARC 1 or 2). There was no significant difference in inhospital death (4 of 146
[2.7%] vs 71 of 1281 [2.0%]; P=.56), but patients with thrombocytopenia had
higher rates of platelet and red blood cell transfusion (18 of 146 [12.3%] vs 93
of 1281 [7.2%]; P=.05). During long-term follow-up, Kaplan-Meier estimated rates
of bleeding events (BARC >=2) were higher for thrombocytopenia (at 5 years, 7.9%
vs 3.6%; P=.03). Patients with thrombocytopenia had a similar risk of long-term
cardiac mortality, but significantly higher rates of noncardiac mortality (at 5
years, 28% vs 21%; P=.02). CONCLUSION: This study suggests that short-term
outcomes after PCI in patients with thrombocytopenia were favorable. On long-term
follow-up, thrombocytopenia was associated with a higher risk of long-term
noncardiac mortality and bleeding.
PMID- 27492911
TI - Prophylactic Plasma Transfusion Before Interventional Radiology Procedures Is Not
Associated With Reduced Bleeding Complications.
AB - OBJECTIVE: To determine the association between prophylactic plasma transfusion
and periprocedural red blood cell (RBC) transfusion rates in patients with
elevated international normalized ratio (INR) values undergoing interventional
radiology procedures. PATIENTS AND METHODS: In this retrospective cohort study,
adult patients undergoing interventional radiology procedures with a
preprocedural INR available within 30 days of the procedure during a study period
of January 1, 2009, to December 31, 2013, were eligible for inclusion. Baseline
characteristics, coagulation parameters, transfusion requirements, and procedural
details were extracted. Univariate and multivariable propensity-matched analyses
were used to assess the relationships between prophylactic plasma transfusion and
the outcomes of interest, with a primary outcome assessed a priori of RBC
transfusion occurring during the procedure or within the first 24 hours
postprocedurally. RESULTS: A total of 18,204 study participants met inclusion
criteria for this study, and 1803 (9.9%) had an INR of 1.5 or greater before
their procedure. Of these 1803 patients, 196 patients (10.9%) received
prophylactic plasma transfusion with a median time of 1.9 hours (interquartile
range [IQR], 1.1-3.2 hours) between plasma transfusion initiation and procedure
initiation. In multivariable propensity-matched analysis, plasma administration
was associated with increased periprocedural RBC transfusions (odds ratio, 2.20;
95% CI, 1.38-3.50; P<.001) and postprocedural intensive care unit admission rates
(odds ratio, 2.11; 95% CI, 1.41-3.14; P<.001) as compared with those who were not
transfused preprocedurally. Similar relationships were seen at higher INR
thresholds for plasma transfusion. CONCLUSION: In patients undergoing
interventional radiology procedures, preprocedural plasma transfusions given in
the setting of elevated INR values were associated with increased periprocedural
RBC transfusions. Additional research is needed to clarify this potential
association between preprocedural plasma transfusion and periprocedural RBC
transfusion.
PMID- 27492912
TI - Patient, Caregiver, and Physician Work in Heart Failure Disease Management: A
Qualitative Study of Issues That Undermine Wellness.
AB - OBJECTIVE: To identify factors underlying heart failure hospitalization. METHODS:
Between January 1, 2012, and May 31, 2012, we combined medical record reviews and
cross-sectional qualitative interviews of multiple patients with heart failure,
their clinicians, and their caregivers from a large academic medical center in
the Midwestern United States. The interview data were analyzed using a 3-step
grounded theory-informed process and constant comparative methods. Qualitative
data were compared and contrasted with results from the medical record review.
RESULTS: Patient nonadherence to the care plan was the most important contributor
to hospital admission; however, reasons for nonadherence were complex and
multifactorial. The data highlight the importance of patient education for the
purposes of condition management, timeliness of care, and effective communication
between providers and patients. CONCLUSION: To improve the consistency and
quality of care for patients with heart failure, more effective relationships
among patients, providers, and caregivers are needed. Providers must be pragmatic
when educating patients and their caregivers about heart failure, its treatment,
and its prognosis.
PMID- 27492913
TI - Incidence of Type 1 Diabetes Is Not Increasing in a Population-Based Cohort in
Olmsted County, Minnesota, USA.
AB - OBJECTIVES: To investigate the recent incidence of T1D in a US Midwestern county
to determine whether this increase has been sustained and compare it with the
incidence of celiac disease (CD) and also investigate the prevalence of CD, an
associated autoimmune disease, within the cohort. PATIENTS AND METHODS: A broad
search strategy was used to identify all incident cases of T1D in Olmsted County,
Minnesota, between January 1, 1994, and December 31, 2010, using the Rochester
Epidemiology Project. Diagnosis and residency status were confirmed through the
medical record. Incidence rates were directly standardized to the 2010 US
population. Poisson regression was used to test for a change in incidence rate.
Clinical charts were reviewed to confirm case status. RESULTS: There were 233
incident cases of T1D. Directly adjusting for age and sex with respect to the
2010 US white population, the overall annual incidence of T1D was 9.2 (95% CI,
8.0-10.4) per 100,000 people per year among all ages and 19.9 (95% CI, 16.6-23.2)
per 100,000 people per year for those younger than 20 years. There was no
significant increase in the incidence of T1D over time (P=.45). Despite the
overall stability in annual incidence, there was an initial increasing trend
followed by a plateau. Of the 109 patients with T1D (47%) tested for CD, 12% (13)
had biopsy-proven CD. CONCLUSION: The incidence of T1D has stopped increasing in
Olmsted County, Minnesota, in the most recent decade. Further studies are needed
to confirm this finding and explore reasons for this plateau.
PMID- 27492914
TI - Duration of Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in
Patients With and Without Acute Coronary Syndrome: A Systematic Review of
Randomized Controlled Trials.
AB - In this systemic review we evaluated the efficacy and safety of long duration
dual anti-platelet therapy (DAPT) (L-DAPT) compared with short duration DAPT (S
DAPT) after drug-eluting stent (DES) implantation in patients who presented with
or without acute coronary syndromes (ACS). We identified 8 randomized controlled
trials in which 30,975 patients were randomized to S-DAPT versus L-DAPT (12,421
ACS and 18,554 non-ACS). Short duration dual anti-platelet therapy was associated
with an increase in target vessel revascularization (TVR) in ACS patients, but
the difference was not significant for non-ACS patients (odds ratio [OR] 5.04
[95% CI, 1.28-19.76], and OR, 0.89 [95% CI, 0.51-1.55], respectively). The risk
of cardiac mortality was not significantly different with S-DAPT and L-DAPT for
ACS (OR, 1.69 [95% CI, 0.82-3.50]) and non-ACS patients (OR, 0.89 [95% CI, 0.57
1.37]). For all cause mortality, myocardial infarction, and stent thrombosis,
most of the events were derived from the DAPT study, thus a meta-analysis was not
performed for these end points. Based on our review of the literature, we
conclude that S-DAPT was associated with higher rates of stent thrombosis and
myocardial infarction, and non-significant differences in all-cause mortality,
with no significant interactions according to ACS vs non-ACS. However, in non-ACS
patients, the benefit-risk profile favored S-DAPT, with lower all-cause
mortality, whereas the trends were reversed in ACS. Additional studies are
required to determine if the benefit-risk profile of S-DAPT vs L-DAPT varies
according to clinical syndrome.
PMID- 27492915
TI - Gas and Bloating-Controlling Emissions: A Case-Based Review for the Primary Care
Provider.
AB - The evaluation of the patient with gas and bloating can be complex and the
treatment extremely challenging. In this article, a simplified approach to the
history and relevant physical examination is presented and applied in a case
oriented manner, suitable for application in the primary care setting.
PMID- 27492916
TI - Common Functional Gastroenterological Disorders Associated With Abdominal Pain.
AB - Although abdominal pain is a symptom of several structural gastrointestinal
disorders (eg, peptic ulcer disease), this comprehensive review will focus on the
4 most common nonstructural, or functional, disorders associated with abdominal
pain: functional dyspepsia, constipation-predominant and diarrhea-predominant
irritable bowel syndrome, and functional abdominal pain syndrome. Together, these
conditions affect approximately 1 in 4 people in the United States. They are
associated with comorbid conditions (eg, fibromyalgia and depression), impaired
quality of life, and increased health care utilization. Symptoms are explained by
disordered gastrointestinal motility and sensation, which are implicated in
various peripheral (eg, postinfectious inflammation and luminal irritants) and/or
central (eg, stress and anxiety) factors. These disorders are defined and can
generally be diagnosed by symptoms alone. Often prompted by alarm features,
selected testing is useful to exclude structural disease. Identifying the
specific diagnosis (eg, differentiating between functional abdominal pain and
irritable bowel syndrome) and establishing an effective patient-physician
relationship are the cornerstones of therapy. Many patients with mild symptoms
can be effectively managed with limited tests, sensible dietary modifications,
and over-the-counter medications tailored to symptoms. If these measures are not
sufficient, pharmacotherapy should be considered for bowel symptoms (constipation
or diarrhea) and/or abdominal pain; opioids should not be used. Behavioral and
psychological approaches (eg, cognitive behavioral therapy) can be helpful,
particularly in patients with chronic abdominal pain who require a
multidisciplinary pain management program without opioids.
PMID- 27492917
TI - Management of Hormone Deprivation Symptoms After Cancer.
AB - Cancer survivors often experience symptoms related to hormone deprivation,
including vasomotor symptoms, genitourinary symptoms, and sexual health concerns.
These symptoms can occur due to natural menopause in midlife women, or they can
be brought on by oncologic therapies in younger women or men. We searched PubMed
for English-language studies from January 1990 through January 2016 to identify
relevant articles on the management of hormone deprivation symptoms, including
vasomotor, genitourinary, and sexual symptoms in patients with cancer. The search
terms used included hormone deprivation, vasomotor symptoms, hot flash, vaginal
dryness, sexual dysfunction, and breast cancer. This manuscript provides a
comprehensive description of data supporting the treatment of symptoms associated
with hormone deprivation.
PMID- 27492918
TI - Gene Expression Profiling in Cutaneous Melanoma: Caveats for Clinicians.
PMID- 27492919
TI - Time in Range: A Fourth Domain in Glycemic Control or a Glucose Variability
Alternative?
PMID- 27492920
TI - Yellowish Papules on the Palms After Water Immersion.
PMID- 27492921
TI - Alzheimer Disease.
PMID- 27492922
TI - The Mighty Mississippi, Summer Day, Morning on Monhegan, and Painting on Warf by
Ken DeWaard.
AB - Recognizing the contribution art has had in the Mayo Clinic environment since the
original Mayo Clinic Building was finished in 1914, Mayo Clinic Proceedings
features some of the numerous works of art displayed throughout the buildings and
grounds on Mayo Clinic campuses as researched and interpreted by the author.
PMID- 27492923
TI - Electroretinographic evaluations of retinal function before, just after, and
after intravitreal injections.
AB - Intravitreal injections (IVI) have become a part of daily practice for a growing
number of procedures. We evaluated the retinal function by recording
intraoperative photopic electroretinograms (ERGs) before an injection (T1), just
after the injection (T2), and after the aspiration of the anterior chamber fluid
(T3) of 19 eyes of 19 patients (mean age 70.6 years; men = 11) who received an
IVI of an anti-vascular endothelial growth factor. The mean amplitudes of the b
wave, photopic negative responses (PhNR), and oscillatory potentials (OPs) 1 and
2 at T2 were significantly smaller than that at T1, but no significant difference
was observed between T3 and T1. The mean implicit times of the a-wave and OP1, 2,
and 3 at T2 and the a-wave and the OP2 at T3 were significantly longer than that
at T1. The mean intraocular pressure (IOP) at T2 (49.32 mm Hg) was significantly
higher and the IOP at T3 (8.74 mm Hg) was significantly lower than that at T1
(21.05 mm Hg). The retinal function was reduced and the IOP elevated just after
the IVI. The response of each ERG component was different suggesting a different
sensitivity of each type of retinal neuron to IVI.
PMID- 27492924
TI - The AMP analog AICAR modulates the Treg/Th17 axis through enhancement of fatty
acid oxidation.
AB - T cells must tightly regulate their metabolic processes to cope with varying
bioenergetic demands depending on their state of differentiation. The metabolic
sensor AMPK is activated in states of low energy supply and modulates cellular
metabolism toward a catabolic state. Although this enzyme is known to be
particularly active in regulatory T (Treg) cells, its impact on T helper (Th)
cell differentiation is poorly understood. We investigated the impact of several
AMPK activators on Treg-cell differentiation and found that the direct activator
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), but not the indirect
activators metformin and 2-deoxyglucose, strongly enhanced Treg-cell induction by
specifically enhancing Treg-cell expansion. Conversely, Th17 generation was
impaired by the agent. Further investigation of the metabolic background of our
observations revealed that AICAR enhanced both cellular mitochondrogenesis and
fatty acid uptake. Consistently, increased Treg induction was entirely reversible
on inhibition of fatty acid oxidation, thus confirming the dependence of AICAR's
effects on metabolic pathways alterations. Translating our findings to an in vivo
model, we found that the substance enhanced Treg cell generation on IL-2 complex
induced immune stimulation. We provide a previously unrecognized insight into the
delicate interplay between immune cell function and metabolism and delineate a
potential novel strategy for metabolism-targeting immunotherapy.-Gualdoni, G. A.,
Mayer, K. A., Goschl, L., Boucheron, N., Ellmeier, W., Zlabinger, G. J. The AMP
analog AICAR modulates the Treg/Th17 axis through enhancement of fatty acid
oxidation.
PMID- 27492926
TI - Ethics, Methods, and Measures in Intimate Partner Violence Research: The Current
State of the Field.
AB - Although intimate partner violence (IPV) is a well-studied topic, surprisingly
little consensus among researchers has been reached with regard to the definition
and measurement of its major typologies and constructs. The rigorous development
and testing of prevention and intervention strategies on a large scale are
hampered by many of these methodological difficulties as well as ethical
considerations that make conducting IPV research difficult. The author presents a
review of the current state of IPV research in these three areas (ethics,
methods, and measurement) with suggestions for innovative research possibilities
building from this status quo. Moving the field of IPV research forward is
necessary to establish a broader evidence base for the prevention and treatment
of abuse and to improve outcomes for survivors of IPV.
PMID- 27492927
TI - "You Are a Part of the Solution": Negotiating Gender-Based Violence and
Engendering Change in Urban Informal Settlements in Mumbai, India.
AB - This article explores how women front-line workers engage with domestic and
gender-based violence in the urban informal settlements of Dharavi in Mumbai,
India. We conducted in-depth interviews with 13 voluntary front-line workers,
along with ethnographic fieldwork in Dharavi, as a part of a pilot study. Our
findings contribute to literature on context-specific approaches to understanding
gender-based violence and "models" to prevent domestic violence in urban micro
spaces. Furthermore, we also discuss notions of "change" ( badlaav) that the
front-line workers experience. Finally, this article presents implications for
socially engaged ethnographic research, as well as contextual and grounded
insights on ways to reduce gender-based and domestic violence.
PMID- 27492925
TI - A novel sphingomyelin/cholesterol domain-specific probe reveals the dynamics of
the membrane domains during virus release and in Niemann-Pick type C.
AB - We identified a novel, nontoxic mushroom protein that specifically binds to a
complex of sphingomyelin (SM), a major sphingolipid in mammalian cells, and
cholesterol (Chol). The purified protein, termed nakanori, labeled cell surface
domains in an SM- and Chol-dependent manner and decorated specific lipid domains
that colocalized with inner leaflet small GTPase H-Ras, but not K-Ras. The use of
nakanori as a lipid-domain-specific probe revealed altered distribution and
dynamics of SM/Chol on the cell surface of Niemann-Pick type C fibroblasts,
possibly explaining some of the disease phenotype. In addition, that nakanori
treatment of epithelial cells after influenza virus infection potently inhibited
virus release demonstrates the therapeutic value of targeting specific lipid
domains for anti-viral treatment.-Makino, A., Abe, M., Ishitsuka, R., Murate, M.,
Kishimoto, T., Sakai, S., Hullin-Matsuda, F., Shimada, Y., Inaba, T., Miyatake,
H., Tanaka, H., Kurahashi, A., Pack, C.-G., Kasai, R. S., Kubo, S., Schieber, N.
L., Dohmae, N., Tochio, N., Hagiwara, K., Sasaki, Y., Aida, Y., Fujimori, F.,
Kigawa, T., Nishibori, K., Parton, R. G., Kusumi, A., Sako, Y., Anderluh, G.,
Yamashita, M., Kobayashi, T., Greimel, P., Kobayashi, T. A novel
sphingomyelin/cholesterol domain-specific probe reveals the dynamics of the
membrane domains during virus release and in Niemann-Pick type C.
PMID- 27492928
TI - Nanomechanical sandwich assay for multiple cancer biomarkers in breast cancer
cell-derived exosomes.
AB - The use of exosomes as cancer diagnostic biomarkers is technically limited by
their size, heterogeneity and the need for extensive purification and labelling.
We report the use of cantilever arrays for simultaneous detection of multiple
exosomal surface-antigens with high sensitivity and selectivity. Exosomes from
breast cancer were selectively identified by detecting over-expressed membrane
proteins CD24, CD63, and EGFR. Excellent selectivity however, was achieved when
targeting the cell-surface proteoglycan, Glypican-1 at extraordinary limits (~200
exosomes per mL, ~0.1 pg mL(-1)).
PMID- 27492929
TI - Omnidirectional surface wave cloak using an isotropic homogeneous dielectric
coating.
AB - The field of transformation optics owes a lot of its fame to the concept of
cloaking. While some experimental progress has been made towards free-space
cloaking in three dimensions, the material properties required are inherently
extremely difficult to achieve. The approximations that then have to be made to
allow fabrication produce unsatisfactory device performance. In contrast, when
surface wave systems are the focus, it has been shown that a route distinct from
those used to design free-space cloaks can be taken. This results in very simple
solutions that take advantage of the ability to incorporate surface curvature.
Here, we provide a demonstration in the microwave regime of cloaking a bump in a
surface. The distortion of the shape of the surface wave fronts due to the
curvature is corrected with a suitable refractive index profile. The surface wave
cloak is fabricated from a metallic backed homogeneous dielectric waveguide of
varying thickness, and exhibits omnidirectional operation.
PMID- 27492930
TI - Investigation of Disability Level, Leisure Satisfaction, and Quality of Life in
Disabled Employees.
AB - The purpose of this study is to investigate the disability level, leisure
satisfaction, and quality of life in employees who were disabled. Six hundred
twenty-seven employees who were disabled were included in this study and
classified according to age, gender and disability level. In quality of life,
there was significant difference between genders and age groups (p < .05). There
was no significant difference neither in leisure satisfaction nor in disability
level between groups (p > .05). In disability assessment, males were better and
there was a significant difference in leisure satisfaction (p < .05). Age,
gender, and disability level were important factors affecting disability, leisure
satisfaction, and quality of life among employees who were disabled.
PMID- 27492931
TI - Strength and Comprehensiveness of School Wellness Policies in Southeastern US
School Districts.
AB - BACKGROUND: In 2004, Congress passed legislation mandating that all public school
districts participating in federal school meal programs develop a school wellness
policy (SWP) to direct efforts related to nutrition and physical activity. We
examined the extent to which SWPs varied in comprehensiveness and strength in a
representative sample of school districts in the southeastern United States, the
area of the country with the highest rates of childhood obesity. METHODS:
Policies were assessed using an established 96-item coding tool by 2 raters to
ascertain the comprehensiveness and strength of the policies as a whole, and
across distinct subsections specified by federal legislation. In addition,
variability in SWP comprehensiveness and strength was assessed based on district
sociodemographic characteristics. RESULTS: Overall, SWPs in the southeastern
states are weakly written, fragmented, and lack requirements necessary for
healthy school environments. District size, which was the only sociodemographic
factor related to policy characteristics, yielded an inverse association.
CONCLUSIONS: To encourage continued promotion of healthy school environments,
school districts will require technical support to improve the quality of their
school wellness policies.
PMID- 27492932
TI - Associations Between Adolescents' Weight and Maladjustment Differ With Deviation
From Weight Norms in Social Contexts.
AB - BACKGROUND: In line with the reflected self-appraisal hypothesis, previous
research finds associations between weight and maladjustment are strongest when
there is a mismatch between individuals' weight and the weight norm of their
social contexts. However, research has not considered associations in more
proximal social contexts. We examined differences in associations between weight
and maladjustment for 2 proximal social contexts: grade-level peers and
friendship groups. METHODS: We used sixth-graders (N = 565; Mage = 12 years)
self-reported height and weight (used to calculate body mass index (BMI) z
score), experiences of peer victimization, and depressive symptoms. Deviation
from the normative weight was calculated as the students' BMI z-score minus the
average BMI z-score for the context (grade-level peers or friendship group).
RESULTS: Considering deviations from grade-level peers, greater BMI z-scores were
associated with more self-reported peer victimization only for students above the
weight norm. For the friendship group, greater weight was associated with more
self-reported depressive symptoms only for those who were above the normative
weight. CONCLUSIONS: Being heavier during adolescence may be especially
problematic for students who differ from the norm in their proximal social
contexts. Intervention efforts focused on weight and maladjustment may want to
consider the contexts involved in adolescents' self-appraisals.
PMID- 27492933
TI - "Headache Tools to Stay in School": Assessment, Development, and Implementation
of an Educational Guide for School Nurses.
AB - BACKGROUND: Headache is the most common type of pain reported in the pediatric
population, and chronic headache is an increasingly prevalent and debilitating
pain condition in children and adolescents. With large numbers of students
experiencing acute headaches and more students with chronic headache reentering
typical school settings, greater availability of tailored evidence-based practice
guidelines for school nurses is imperative. METHODS: A 2-armed study was
developed to assess the need for and evaluate the use and favorability of a
headache-driven school nurse guide. Students and their parents were first
surveyed on their school nurse's headache knowledge and management skills. School
nurses were also interviewed on their desire for a headache educational tool.
This feedback aided in developing a headache resource guide. Next, the guide was
distributed to school nurses who provided feedback after a 3-month trial.
RESULTS: Results indicate that "Headache Tools to Stay in School" is a useful
resource in facilitating communication among health care providers, students,
families, and school personnel on how to best meet the complex needs of students
with headaches. CONCLUSIONS: Given the guide's favorability, we encourage school
nurses to demand the creation of additional evidence-based resources. Continued
dissemination of this guide may improve students' headache management under the
informed care of school nurses, and may encourage the development of more
evidence-based guides across various medical conditions.
PMID- 27492934
TI - Bigger ? Better: The Comprehensiveness and Strength of School Wellness Policies
Varies by School District Size.
AB - BACKGROUND: District size has been shown to impact the anticipated barriers to
wellness policy creation and implementation. Therefore, the purpose of the
present study was to determine if strength and comprehensiveness of wellness
policies differs among school districts of varying size. METHODS: Wellness
policies were collected from 10 large, 29 medium, and 31 small school districts
in a rural Midwest state. District size was categorized by the average daily
membership in grades 9-11. Polices were coded using the Wellness School
Assessment Tool (WellSAT). Strength and comprehensiveness of the full policy and
policy sections were compared among small, medium, and large districts using 1
way analyses of variance (ANOVAs). Data are presented as mean +/- SD. Statistical
significance was set at p <= .05. RESULTS: There was a difference in the total
combined (p = .041), total comprehensiveness (p = .043), and total strength
scores (p = .031) based on school district size, such that small districts had
stronger, more comprehensive wellness policies than large districts. Section
comparisons revealed the section focused on Standards for United States
Department of Agriculture School Meals was primarily responsible for these
differences. CONCLUSIONS: These data suggest smaller districts write policies
that are more comprehensive to governmental standards and use more definitive
language than larger districts.
PMID- 27492935
TI - Support for Offering Sexual Health Services Through School-Based Health Clinics.
AB - BACKGROUND: Numerous studies document support for sexuality education in the
schools. However, there is a dearth of research assessing support for sexual
health services offered through school-based health clinics (SBHCs). The purpose
of this study was to assess voter support for offering 3 sexual health services
(STI/HIV testing, STI/HIV treatment, condom distribution) through SBHCs. METHODS:
The survey was developed after review of existing surveys on support for
sexuality education and sexual health services. The university's Public Opinion
Research Laboratory used random-digit-dialing to administer the survey to
participants (N = 311) including residential and cell phone numbers. RESULTS:
Most participants were supportive of offering sexual health services at both
middle schools (MS) and high schools (HS): testing for STIs/HIV (61% MS, 76% HS),
treatment for STIs/HIV (60% MS, 75% HS), and provision of condoms (44% MS, 63%
HS). Analyses showed significant differences in support for sexual health
services by a few demographic variables, opinions about sexuality education, and
the percentage of students perceived to have had sexual intercourse. CONCLUSIONS:
Results document support for offering sexual health services through SBHCs. These
findings may benefit other communities looking to implement similar clinics. Such
services have great potential for positively impacting the sexual health of
youth.
PMID- 27492936
TI - Implementation in Practice: Adaptations to Sexuality Education Curricula in
California.
AB - BACKGROUND: Local implementation of evidence-based curricula, including sex
education, has received increasing attention. Although there are expectations
that practitioners will implement evidence-based programs with fidelity, little
is known regarding the experiences of instructors in meeting such standards.
During 2005 to 2009, the California Department of Public Health funded local
agencies through its Teen Pregnancy Prevention Programs (TPP) to provide
comprehensive sex education. METHODS: To improve understanding of how agencies
implemented curricula, in-depth telephone interviews with 128 coordinators were
conducted in 2008 to 2009. Qualitative data were analyzed for content and themes.
Selected data were quantified and analyzed to examine differences in curriculum
adaptations across settings and curricula type. RESULTS: Whereas over half of the
TPP agencies (59%) implemented evidence-based curricula, most agencies (95%)
reported adapting the curriculum, with the majority (83%) adding content. Reasons
for adaptations included ensuring that the material was accurate and appropriate;
responding to logistical or time constraints; and other factors, such as parental
and institutional support. CONCLUSION: These adaptations reflected agencies'
efforts to balance state and local requirements, maintain curriculum fidelity,
and provide more up-to-date and accessible information. These experiences
highlight the need for guidelines that enable appropriate adaptations, while
maintaining fidelity to the core components of the original curriculum.
PMID- 27492937
TI - Reliability and Validity of the PAQ-C Questionnaire to Assess Physical Activity
in Children.
AB - BACKGROUND: Physical activity (PA) assessment by questionnaire is a cornerstone
in the field of sport epidemiology studies. The Physical Activity Questionnaire
for Children (PAQ-C) has been used widely to assess PA in healthy school
populations. The aim of this study was to evaluate the reliability and validity
of the PAQ-C questionnaire in Spanish children using triaxial accelerometry as
criterion. METHODS: Eighty-three (N = 46 boys, N = 37 girls) healthy children
(age 10.98 +/- 1.17 years, body mass index 19.48 +/- 3.51 kg/m(2) ) were
volunteers and completed the PAQ-C twice and wore an accelerometer for 8
consecutive days. Reliability was analyzed by the intraclass correlation
coefficient (ICC) and the internal consistency by the Cronbach's alpha
coefficient. The PAQ-C was compared against total PA and moderate to vigorous PA
(MVPA) obtained by accelerometry. RESULTS: Test-retest reliability showed an ICC
= 0.96 for the final score of PAQ-C. Small differences between first and second
questionnaire administration were detected. Few and low correlations (rho = 0.228
0.278, all ps < .05) were observed between PAQ-C and accelerometry. The highest
correlation was observed for item 9 (rho = 0.311, p < .01). CONCLUSIONS: PAQ-C
had a high reliability but a questionable validity for assessing total PA and
MVPA in Spanish children. Therefore, PA measurement in children should not be
limited only to self-report measurements.
PMID- 27492938
TI - Association Between Physical Fitness and Academic Achievement in a Cohort of
Danish School Pupils.
AB - BACKGROUND: Time spent on physical activity in elementary school has been altered
to improve core academics. However, little is known about the relationship
between physical fitness and academic achievement. We examined the association
between physical fitness and academic achievement and investigated the influence
of parental socioeconomic status and ethnicity. METHODS: Participants were 542
girls and 577 boys aged 13 to 15 residing in the Danish municipality of Aalborg.
A watt-max cycle ergometer test was completed to evaluate physical fitness as
represented by VO2 max (mL.kg(-1) .min(-1) ). Academic achievement was measured 1
school year later through a series of mandatory exams within the humanities,
sciences, and all obligatory defined exams. Parental income and education were
drawn from nationwide registers. Linear regression models were used to
investigate the association. RESULTS: Adjusting for ethnicity and parental
socioeconomic status, the effect size of the humanities was 0.08 grad/VO2 max
(95% Cl: 0.05 to 0.11) for girls and 0.06 grad/VO2 max (95% Cl:0.03 to 0.08) for
boys. The effect size of the sciences was 0.09 grad/VO2 max (95% Cl:0.05 to 0.13)
for girls and 0.06 grad/VO2 max (95% Cl:0.03 to 0.09) for boys. The effect size
of the defined exams was 0.09 grad/VO2 max (95% Cl:0.06 to 0.11) for girls and
0.06 grad/VO2 max (95% Cl:0.03 to 0.08) for boys. CONCLUSION: We found a
statistically significant positive association between physical fitness and
academic achievement after adjusting for ethnicity and parental socioeconomic
status.
PMID- 27492939
TI - Blood pressure and complications in individuals with type 2 diabetes and no
previous cardiovascular disease: national population based cohort study.
AB - OBJECTIVES: To compare the risk associated with systolic blood pressure that
meets current recommendations (that is, below 140 mm Hg) with the risk associated
with lower levels in patients who have type 2 diabetes and no previous
cardiovascular disease. DESIGN: Population based cohort study with nationwide
clinical registries, 2006-12. The mean follow-up was 5.0 years. SETTING: 861
Swedish primary care units and hospital outpatient clinics. PARTICIPANTS: 187
106 patients registered in the Swedish national diabetes register who had had
type 2 diabetes for at least a year, age 75 or younger, and with no previous
cardiovascular or other major disease. MAIN OUTCOME MEASURES: Clinical events
were obtained from the hospital discharge and death registers with respect to
acute myocardial infarction, stroke, a composite of acute myocardial infarction
and stroke (cardiovascular disease), coronary heart disease, heart failure, and
total mortality. Hazard ratios were estimated for different levels of baseline
systolic blood pressure with clinical characteristics and drug prescription data
as covariates. RESULTS: The group with the lowest systolic blood pressure (110
119 mm Hg) had a significantly lower risk of non-fatal acute myocardial
infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91;
P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non
fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular
disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88,
0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There
was no indication of a J shaped relation between systolic blood pressure and the
endpoints, with the exception of heart failure and total mortality. CONCLUSIONS:
Lower systolic blood pressure than currently recommended is associated with
significantly lower risk of cardiovascular events in patients with type 2
diabetes. The association between low blood pressure and increased mortality
could be due to concomitant disease rather than antihypertensive treatment.
PMID- 27492940
TI - Preparation and Characterization of Antimony and Arsenic Tricyanide and Their
2,2'-Bipyridine Adducts.
AB - The arsenic(III) and antimony(III) cyanides M(CN)3 (M=As, Sb) have been prepared
in quantitative yields from the corresponding trifluorides through fluoride
cyanide exchange with Me3 SiCN in acetonitrile. When the reaction was carried out
in the presence of one equivalent of 2,2'-bipyridine, the adducts [M(CN)3 ?(2,2'
bipy)] were obtained. The crystal structures of As(CN)3 , [As(CN)3 ?(2,2'-bipy)]
and [Sb(CN)3 ?(2,2'-bipy)] were determined and are surprisingly different.
As(CN)3 possesses a polymeric three-dimensional structure, [As(CN)3 ?(2,2'-bipy)]
exhibits a two-dimensional sheet structure, and [Sb(CN)3 ?(2,2'-bipy)] has a
chain structure, and none of the structures resembles those found for the
corresponding arsenic and antimony triazides.
PMID- 27492941
TI - Cardiac rehabilitation increases physical capacity but not mental health after
heart valve surgery: a randomised clinical trial.
AB - OBJECTIVE: The evidence for cardiac rehabilitation after valve surgery remains
sparse. Current recommendations are therefore based on patients with ischaemic
heart disease. The aim of this randomised clinical trial was to assess the
effects of cardiac rehabilitation versus usual care after heart valve surgery.
METHODS: The trial was an investigator-initiated, randomised superiority trial
(The CopenHeartVR trial, VR; valve replacement or repair). We randomised 147
patients after heart valve surgery 1:1 to 12 weeks of cardiac rehabilitation
consisting of physical exercise and monthly psycho-educational consultations
(intervention) versus usual care without structured physical exercise or psycho
educational consultations (control). Primary outcome was physical capacity
measured by VO2 peak and secondary outcome was self-reported mental health
measured by Short Form-36. RESULTS: 76% were men, mean age 62 years, with aortic
(62%), mitral (36%) or tricuspid/pulmonary valve surgery (2%). Cardiac
rehabilitation compared with control had a beneficial effect on VO2 peak at 4
months (24.8 mL/kg/min vs 22.5 mL/kg/min, p=0.045) but did not affect Short Form
36 Mental Component Scale at 6 months (53.7 vs 55.2 points, p=0.40) or the
exploratory physical and mental outcomes. Cardiac rehabilitation increased the
occurrence of self-reported non-serious adverse events (11/72 vs 3/75, p=0.02).
CONCLUSIONS: Cardiac rehabilitation after heart valve surgery significantly
improves VO2 peak at 4 months but has no effect on mental health and other
measures of exercise capacity and self-reported outcomes. Further research is
needed to justify cardiac rehabilitation in this patient group. TRIAL
REGISTRATION NUMBER: NCT01558765, Results.
PMID- 27492942
TI - Clinical and prognostic value of poststenting fractional flow reserve in acute
coronary syndromes.
AB - OBJECTIVES: Fractional flow reserve (FFR) has been suggested to have value in
acute coronary syndromes (ACSs). The clinical and prognostic value of ischaemia
reduction assessed by post-percutaneous coronary intervention (PCI) FFR has not
been studied in this population. METHODS: Consecutive stable ischaemic heart
disease (SIHD) (N=390) and patients with ACS (N=189) who had pre-PCI FFR and post
PCI FFR were followed for 2.4+/-1.5 years. Primary endpoint was major adverse
cardiac events (MACE) (composite of myocardial infarction, target vessel
revascularisation and death). RESULTS: In patients with ACS, PCI led to
significant improvement in FFR from 0.62+/-0.15 to post-PCI FFR 0.88+/-0.08
(p<0.0001). Post-PCI FFR identified 29 patients (15%) who had persistently low
FFR<0.80 (0.75+/-0.06) despite angiographically optimal results prompting
subsequent interventions improving repeat FFR (0.85+/-0.06; p<0.0001). The
difference in MACE events between patients with ACS and patients with SIHD varied
according to the post-PCI FFR value (interaction p=0.044). Receiver operator
curve analysis identified a final FFR cut-off of <=0.91 as having the best
predictive accuracy for MACE in the ACS study population (30% vs 19%; p=0.03).
Patients with ACS achieving final FFR of >0.91 had similar outcomes compared with
patients who had SIHD (19% vs 16%; p=0.51). However, in patients with final FFR
of <=0.91 there was increased MACE versus patients with SIHD (30% vs 16%;
p<0.01). CONCLUSIONS: Post-PCI FFR is valuable in assessing the functional
outcome of PCI in patients with ACS. Use of post-PCI FFR in patients with ACS
allows for functional optimisation of PCI results and is predictive of long-term
outcomes in patients with ACS.
PMID- 27492943
TI - Left atrial appendage occlusion in high-risk patients with non-valvular atrial
fibrillation.
AB - OBJECTIVE: Percutaneous left atrial appendage (LAA) occlusion has been developed
as a viable option for stroke and thromboembolism prevention in patients with non
valvular atrial fibrillation (NVAF) and at high risk for cerebral cardioembolic
events. Data on device implantation and long-term follow-up from large cohorts
are limited. METHODS: 110 consecutive patients with NVAF and contraindications to
oral anticoagulants (OACs) underwent LAA occlusion procedures and achieved a
longer than 1 year follow-up. All patients were enrolled in a prospective
registry. Procedures were performed using the Amplatzer Cardiac Plug or Amulet
guided by fluoroscopy and intracardiac echocardiography. RESULTS: Mean age of the
population was 77+/-6 years old; 68 were men. Atrial fibrillation was paroxysmal
in 20%, persistent in 15.5% and permanent in 64.5% of cases, respectively. Mean
CHA2DS2-VASc and HAS-BLED scores were 4.3+/-1.3 and 3.4+/-1, respectively.
Technical success (successful deployment and implantation of device) was achieved
in 100% of procedures. Procedural success (technical success without major
procedure-related complications) was achieved in 96.4%, with a 3.6% rate of major
procedural complications (three cases of pericardial tamponade requiring drainage
and one case of major bleeding). Mean follow-up was 30+/-12 months (264 patient
years). Annual rates for ischaemic stroke and for other thromboembolic events
were respectively 2.2% and 0%, and annual rate for major bleeding was 1.1%.
CONCLUSIONS: Our data suggest LAA occlusion in high-risk patients with NVAF not
suitable for OACs is feasible and associated with low complication rates as well
as low rates of stroke and major bleeding at long-term follow-up.
PMID- 27492944
TI - Factors Affecting Attenuation of Dural Sinuses on Noncontrasted Computed
Tomography Scan.
AB - BACKGROUND AND PURPOSE: Noncontrasted computed tomography (NCCT) is used as the
initial neuroimaging test of choice for patients who present with new-onset
neurological symptoms. An apparently hyperattenuated venous sinus may lead to the
suspicion of cerebral venous sinus thrombosis (CVST). Improved understanding of
all factors that can affect attenuation of dural sinuses can guide triage of
patients to or from further investigations of suspected CVST. The purpose of this
retrospective study was to assess the effect of different factors including
hematocrit (HCT), hemoglobin (Hb), age, BUN/Cr ratio (blood urea nitrogen-to
creatinine ratio), and gender on the attenuation of dural sinuses on brain NCCT.
METHODS: A total of 1293 patients with neurological symptoms who presented to the
emergency department were included in this study. For each patient, clinical
assessment, laboratory investigations, and brain NCCT were reviewed. For each
brain NCCT, the average attenuation of superior sagittal sinus and both right and
left sigmoid sinuses was measured. RESULTS: Positive significant correlations
were found between average attenuation of dural sinuses on one hand and each of
age, Hb, and HCT on the other hand. No significant correlation was found between
average attenuation and BUN/Cr ratio. Gender discrepancy was also significant as
higher attenuation was found in men. CONCLUSION: Age, gender, and Hb levels are
the main factors that should be taken into account upon the assessment of dural
sinuses on brain NCCT. The highest normal attenuation is predicted in an elderly
polycythemic man and the lowest is predicted in a young anemic woman.
PMID- 27492945
TI - Medical Decision Making: Hyposphagma Prior to Intravenous Tissue Plasminogen
Activator in Acute Ischemic Stroke.
AB - The decision to administer intravenous tissue plasminogen activator (IV tPA) is
based on standard exclusion and inclusion criteria, which include laboratories,
imaging, and time of last known well. When patients present with a clinical
scenario that is not addressed in these standards, the decision to administer IV
tPA is more complex. We present a case of a patient with an acute stroke syndrome
that also included acute subconjunctival hemorrhage (i.e., hyposphagma). We
provide the medical decision making that occurred prior to the administration.
Ultimately, the finding of hyposphagma should not disqualify eligible patients
from receiving IV tPA.
PMID- 27492946
TI - Detection of Atrial Fibrillation with Intermittent Handheld Electrocardiogram in
Patients with Ischemic Stroke and Transient Ischemic Attack.
AB - BACKGROUND: Atrial fibrillation is an important risk factor for recurrent
ischemic stroke and transient ischemic attack. Despite routine investigation,
some patients' atrial fibrillation remains undetected. Intermittent handheld
electrocardiogram (ECG) is an option for extended ECG monitoring aiming at
enhancing detection rates. This study aimed to explore the detection rate of
atrial fibrillation in stroke and transient ischemic attack patients with
intermittent handheld ECG in the clinical setting of Halland Hospital Halmstad.
METHODS: Patients discharged with a diagnosis of ischemic stroke or transient
ischemic attack who underwent intermittent handheld ECG recording at Halland
Hospital Halmstad from January 1, 2010, to March 31, 2014, were retrospectively
studied; 370 patients in total. A positive investigation was defined as either
atrial fibrillation for a minimum of 10 seconds or a short irregular
supraventricular run. RESULTS: We found an overall atrial fibrillation detection
rate of 7.6% (95% CI 5.1%-10.1%). The detection rate in stroke patients (11.0%)
was significantly higher than in transient ischemic attack patients (5.0%), P =
.032. The detection rate in patients aged less than 65 years was 4.2%, increasing
to 9.8% in patients aged 65 years or older, P = .051. CONCLUSION: This
retrospective study shows an atrial fibrillation detection rate of 7.6% in a
stroke and transient ischemic attack population using prolonged intermittent
monitoring with handheld ECG recording. The compliance to the monitoring was
excellent.
PMID- 27492947
TI - Continuous Monitoring of Spreading Depolarization and Cerebrovascular
Autoregulation after Aneurysmal Subarachnoid Hemorrhage.
AB - Delayed cerebral ischemia (DCI) is a prominent complication after aneurysmal
subarachnoid hemorrhage (aSAH). Although vasospasm of proximal cerebral arteries
has been regarded as the main cause of DCI, vasospasm of distal arteries,
microthrombosis, impaired autoregulation, cortical spreading depolarization
(CSD), and spreading ischemia are thought to be involved in DCI after aSAH. Here,
we describe a patient with aSAH in whom CSD and cerebrovascular autoregulation
were evaluated using simultaneous electrocorticography and monitoring of the
pressure reactivity index (PRx) after surgical clipping of a ruptured posterior
communicating artery aneurysm. In this patient, a prolonged duration of CSD and
elevation of PRx preceded delayed neurological deficit. Based on this
observation, we propose a relationship between these factors and DCI. Assessment
of cerebrovascular autoregulation may permit detection of the inverse hemodynamic
response to cortical depolarization. Detection of DCI may be achieved through
simultaneous monitoring of CSD and PRx in patients with aSAH.
PMID- 27492948
TI - Influence of sonophoresis on transdermal drug delivery of hydrophilic compound
loaded lipid nanocarriers.
AB - The effect of sonophoresis on the transdermal drug delivery of sodium fluorescein
(NaFI)-loaded lipid nanocarriers such as liposomes (LI), niosomes (NI) and solid
lipid nanoparticles (SLN) was investigated by confocal laser scanning microscopy
(CLSM), fourier transform infrared spectroscopy (FTIR) and scanning electron
microscopy (SEM). The results showed that SN decreased the skin penetration of
NaFI-loaded SLN (6.32-fold) and NI (1.79-fold), while it increased the
penetration of NaFI-loaded LI (5.36-fold). CLSM images showed the red
fluorescence of the LI and NI bilayer on the superficial layer of the stratum
corneum. However, the red fluorescent probe of the SLN was not visualized in the
skin. FTIR results of the LI and NI with SN showed no effect on lipid stratum
corneum ordering, suggesting that the fragment of bilayer vesicles might repair
the damaged skin. For SLN, the strengthening of stratum corneum by covering the
disrupted skin with solid lipids was shown. SEM images show disrupted carriers of
all the formulations adsorbed onto the damaged skin. In conclusion, the SN
changed the properties of both the skin surface and lipid nanocarrier,
demonstrating that disrupted skin might be repaired by a disrupted nanocarrier.
PMID- 27492949
TI - An atypical role for the myeloid receptor Mincle in central nervous system
injury.
AB - The C-type lectin Mincle is implicated in innate immune responses to sterile
inflammation, but its contribution to associated pathologies is not well
understood. Herein, we show that Mincle exacerbates neuronal loss following
ischemic but not traumatic spinal cord injury. Loss of Mincle was beneficial in a
model of transient middle cerebral artery occlusion but did not alter outcomes
following heart or gut ischemia. High functional scores in Mincle KO animals
using the focal cerebral ischemia model were accompanied by reduced lesion size,
fewer infiltrating leukocytes and less neutrophil-derived cytokine production
than isogenic controls. Bone marrow chimera experiments revealed that the
presence of Mincle in the central nervous system, rather than recruited immune
cells, was the critical regulator of a poor outcome following transient middle
cerebral artery occlusion. There was no evidence for a direct role for Mincle in
microglia or neural activation, but expression in a subset of macrophages
resident in the perivascular niche provided new clues on Mincle's role in
ischemic stroke.
PMID- 27492951
TI - Translational Relevance of Swine Models of Spinal Cord Injury.
AB - Spinal cord injury (SCI) is a physically and psychologically devastating clinical
condition. The typical treatment regimens of decompressive surgery and
rehabilitation therapy still leave many patients with permanent disability. The
development of new therapies and devices can be accelerated if relevant
translational animal models are more effectively used in pre-clinical stages.
Swine is a highly relevant model for SCI research, especially with respect to
spine and spinal cord anatomy, spine vasculature, immune responses to injury, and
functional assessments. Several spine injury models have recently been developed
for swine and are beginning to be used to evaluate new therapies. Swine models of
SCI offer tremendous advantages for efficient translation of pre-clinical
discoveries and the development of new therapies and devices. Future swine models
will also be enhanced by advances in gene-editing technology to further elucidate
the complex pathophysiology associated with SCI and provide a means to engineer
specific spinal pathologies.
PMID- 27492952
TI - Analytical Eco-Scale for Assessing the Greenness of a Developed RP-HPLC Method
Used for Simultaneous Analysis of Combined Antihypertensive Medications.
AB - In the past few decades the analytical community has been focused on eliminating
or reducing the usage of hazardous chemicals and solvents, in different
analytical methodologies, that have been ascertained to be extremely dangerous to
human health and environment. In this context, environmentally friendly, green,
or clean practices have been implemented in different research areas. This study
presents a greener alternative of conventional RP-HPLC methods for the
simultaneous determination and quantitative analysis of a pharmaceutical ternary
mixture composed of telmisartan, hydrochlorothiazide, and amlodipine besylate,
using an ecofriendly mobile phase and short run time with the least amount of
waste production. This solvent-replacement approach was feasible without
compromising method performance criteria, such as separation efficiency, peak
symmetry, and chromatographic retention. The greenness profile of the proposed
method was assessed and compared with reported conventional methods using the
analytical Eco-Scale as an assessment tool. The proposed method was found to be
greener in terms of usage of hazardous chemicals and solvents, energy
consumption, and production of waste. The proposed method can be safely used for
the routine analysis of the studied pharmaceutical ternary mixture with a minimal
detrimental impact on human health and the environment.
PMID- 27492950
TI - Changes in intracranial venous blood flow and pulsatility in Alzheimer's disease:
A 4D flow MRI study.
AB - Cerebral blood flow, arterial pulsation, and vasomotion may be important
indicators of cerebrovascular health in aging and diseases of aging such as
Alzheimer's disease. Noninvasive markers that assess these characteristics may be
helpful in the study of co-occurrence of these diseases and potential additive
and interacting effects. In this study, 4D flow MRI was used to measure intra
cranial flow features with cardiac-gated phase contrast MRI in cranial arteries
and veins. Mean blood flow and pulsatility index as well as the transit time of
the peak flow from the middle cerebral artery to the superior sagittal sinus were
measured in a total of 104 subjects comprising of four groups: (a) subjects with
Alzheimer's disease, (b) age-matched controls, (c) subjects with mild cognitive
impairment, and (d) a group of late middle-aged with parental history of sporadic
Alzheimer's disease. The Alzheimer's disease group exhibited: a significant
decrease in mean blood flow in the superior sagittal sinus, transverse sinus,
middle cerebral artery, and internal carotid arteries; a significant decrease of
the peak and end diastolic blood flow in the middle cerebral artery and superior
sagittal sinus; a faster transmission of peak flow from the middle cerebral
artery to the superior sagittal sinus and increased pulsatility index along the
carotid siphon.
PMID- 27492953
TI - Posterior Distal Clavicle Beveling for Chronic Nonincarcerated Type IV
Acromioclavicular Separations: Surgical Technique and Early Clinical Outcomes.
AB - PURPOSE: To describe the arthroscopic partial posterior distal clavicle beveling
technique for treatment of chronic nonincarcerated type IV acromioclavicular (AC)
separations and report clinical outcomes and return to sport. METHODS: All
patients who underwent the arthroscopic partial distal clavicle beveling
technique and met eligibility criteria were identified and retrospectively
reviewed. Inclusion criteria included the clinical diagnosis of a chronic
nonincarcerated type IV AC separation and a minimum follow-up period of 24
months. Subjects completed the American Shoulder Elbow Surgeons shoulder
assessment and a study-designed questionnaire. Radiographic images and clinical
charts were also reviewed. RESULTS: This study identified 15 consecutive patients
with 2 lost to follow-up, resulting in inclusion of 13 subjects (9 males and 4
females). Dominant arm was involved in 77% of cases. Mean age at operation was
33.2 years (range, 19-56 years). The mean period between injury and operation was
12.5 months (range, 3-37 months), and follow-up was 48.5 months (range, 24-126
months). The mean preoperative ASES score was 46.6 +/- 16.9 (range, 33-68), and
the mean postoperative ASES score was 87.3 +/- 17.4 (range, 50-100) (P < .0001).
All 9 athletes in the study returned to competition with a mean recovery period
of 2.3 months (range, 2 weeks to 4 months). Mean timeframe for return to work was
2 weeks (range, 1 day to 2 months). One subject underwent a subsequent
coracoclavicular ligament reconstruction for continued pain. The mean
satisfaction level was 4.3 out of 5, and 91% would choose to have the surgery
again. One subject indicated dissatisfaction with shoulder appearance.
CONCLUSIONS: The arthroscopic partial distal clavicle beveling procedure for
nonincarcerated type IV AC separations resulted in a significant reduction in
pain, improved daily function, and early return to sport. LEVEL OF EVIDENCE:
Level IV, therapeutic case series.
PMID- 27492954
TI - Genomic control of neuronal demographics in the retina.
AB - The mature retinal architecture is composed of various types of neuron, each
population differing in size and constrained to particular layers, wherein the
cells achieve a characteristic patterning in their local organization. These
demographic features of retinal nerve cell populations are each complex traits
controlled by multiple genes affecting different processes during development,
and their genetic determinants can be dissected by correlating variation in these
traits with their genomic architecture across recombinant-inbred mouse strains.
Using such a resource, we consider how the variation in the numbers of twelve
different types of retinal neuron are independent of one another, including those
sharing transcriptional regulation as well as those that are synaptically
connected, each mapping to distinct genomic loci. Using the populations of two
retinal interneurons, the horizontal cells and the cholinergic amacrine cells, we
present in further detail examples where the variation in neuronal number, as
well as the variation in mosaic patterning or in laminar positioning, each maps
to discrete genomic loci where allelic variants modulating these features must be
present. At those loci, we identify candidate genes which, when rendered non
functional, alter those very demographic properties, and in turn, we identify
candidate coding or regulatory variants that alter protein structure or gene
expression, respectively, being prospective contributors to the variation in
phenotype. This forward-genetic approach provides an alternative means for
dissecting the molecular genetic control of neuronal population dynamics, with
each genomic locus serving as a causal anchor from which we may ultimately
understand the developmental principles responsible for the control of those
traits.
PMID- 27492955
TI - H-NS: an overarching regulator of the Vibrio cholerae life cycle.
AB - Vibrio cholerae has become a model organism for studies connecting virulence,
pathogen evolution and infectious disease ecology. The coordinate expression of
motility, virulence and biofilm enhances its pathogenicity, environmental fitness
and fecal-oral transmission. The histone-like nucleoid structuring protein
negatively regulates gene expression at multiple phases of the V. cholerae life
cycle. Here we discuss: (i) the regulatory and structural implications of H-NS
chromatin-binding in the two-chromosome cholera bacterium; (ii) the factors that
counteract H-NS repression; and (iii) a model for the regulation of the V.
cholerae life cycle that integrates H-NS repression, cyclic diguanylic acid
signaling and the general stress response.
PMID- 27492961
TI - Novel super-resolution capable mitochondrial probe, MitoRed AIE, enables
assessment of real-time molecular mitochondrial dynamics.
AB - Mitochondria and mitochondrial dynamics play vital roles in health and disease.
With the intricate nanometer-scale structure and rapid dynamics of mitochondria,
super-resolution microscopy techniques possess great un-tapped potential to
significantly contribute to understanding mitochondrial biology and kinetics.
Here we present a novel mitochondrial probe (MitoRed AIE) suitable for live
mitochondrial dynamics imaging and single particle tracking (SPT), together with
a multi-dimensional data analysis approach to assess local mitochondrial
(membrane) fluidity. The MitoRed AIE probe localizes primarily to mitochondrial
membranes, with 95 ms fluorophore on-time delivering 106 photons/ms,
characteristics which we exploit to demonstrate live cell 100 fps 3D time-lapse
tracking of mitochondria. Combining our experimental and analytical approaches,
we uncover mitochondrial dynamics at unprecedented time scales. This approach
opens up a new regime into high spatio-temporal resolution dynamics in many areas
of mitochondrial biology.
PMID- 27492962
TI - Vonoprazan is superior to proton pump inhibitors in healing artificial ulcers of
the stomach post-endoscopic submucosal dissection: A propensity score-matching
analysis.
AB - BACKGROUND AND AIM: Proton pump inhibitors (PPI) are effective at healing
artificial ulcers after endoscopic submucosal dissection (ESD) for gastric
neoplasms; however, the efficacy of vonoprazan is not completely understood. The
aim of the present study was to determine the healing effect of vonoprazan on
artificial ulcers post-gastric ESD relative to PPI. METHODS: Thirty-five patients
who underwent gastric ESD between April and November 2015 were treated with
vonoprazan 20 mg/day for 4 weeks and subsequently underwent endoscopy for
evaluation of ulcer size (V group). Ulcer contraction rate was determined by the
following formula: ([ESD specimen size] - [ulcer size at 4 weeks after ESD])/(ESD
specimen size) * 100%. We compared the results with those of a historical control
group treated with esomeprazole 20 mg/day for 4 weeks after gastric ESD and
subsequently measured their ulcer size (33 patients, E group) by propensity score
matching methods. RESULTS: Sixty-two subjects were enrolled after propensity
score-matching. Ulcer contraction rate at 4 weeks after ESD in the V group was
significantly higher than that of the E group (97.7 +/- 3.2% vs 94.5 +/- 6.7%,
respectively, P = 0.025). Number of subjects with a scar-stage ulcer (100%
contraction rate) tended to be higher in the V group relative to the E group (32%
[10 of 31] vs 13% [4 of 31], respectively, P = 0.070, McNemar's chi-squared
test). CONCLUSION: Vonoprazan has a faster post-gastric ESD artificial ulcer
contraction rate than esomeprazole. Vonoprazan may supersede PPI in treating post
ESD artificial ulcers of the stomach.
PMID- 27492963
TI - Isolation and Physical Property Optimization of an Amorphous Drug Substance
Utilizing a High Surface Area Magnesium Aluminometasilicate (Neusilin((r)) US2).
AB - Control and optimization of the physical properties of a drug substance (DS) are
critical to the development of robust drug product manufacturing processes and
performance. A lack of isolatable, for example, crystalline, DS solid forms can
present challenges to achieving this control. In this study, an isolation scheme
for an amorphous DS was developed and integrated into the synthetic route
producing DS with optimized properties. An inert absorbent excipient (Neusilin(r)
US2) was used to isolate the DS via a novel antisolvent scheme as the final step
of the route. Isolation was executed at kilogram scale utilizing conventional
equipment. The resulting 50 wt% DS:Neusilin complex had improved physical
stability and exceptional micromeritic and tableting properties. Improved
dissolution was observed and attributed to enhanced dispersion and increased
surface area. Characterization data suggest a high degree of penetration of the
DS into the Neusilin, with DS occupying 70% of mesopore and 12% of macropore
volume. This approach has application in the isolation and particle engineering
of difficult to isolate DS without additional unit operation, such as spray
drying, and has the potential for a high degree of optimization and control of
physical properties over the course of DS development.
PMID- 27492964
TI - Medication-induced diabetes mellitus.
AB - Epidemiological studies and case reports have demonstrated an increased rate of
development of diabetes mellitus consequent to taking diverse types of
medication. This review explores this evidence linking these medications and
development of diabetes and presents postulated mechanisms by which the
medications might cause diabetes. Some medications are associated with a
reduction in insulin production, some with reduction in insulin sensitivity, and
some appear to be associated with both reduction in insulin production and
insulin sensitivity.
PMID- 27492965
TI - Agonist-induced internalization and desensitization of the apelin receptor.
AB - Apelin acts via the G protein-coupled apelin receptor (APJ) to mediate effects on
cardiovascular and fluid homeostasis. G protein-coupled receptor (GPCR)
trafficking has an important role in the regulation of receptor signalling
pathways and cellular functions, however in the case of APJ the mechanisms and
proteins involved in apelin-induced trafficking are not well understood. We
generated a stable HEK-293 cell line expressing N-terminus HA-tagged mouse (m)
APJ, and used a semi-automated imaging protocol to quantitate APJ trafficking and
ERK1/2 activation following stimulation with [Pyr1]apelin-13. The mechanisms of
[Pyr1]apelin-13-induced internalization and desensitization were explored using
dominant-negative mutant (DNM) cDNA constructs of G protein-coupled receptor
kinase 2 (GRK2), beta-arrestin1, EPS15 and dynamin. The di-phosphorylated ERK1/2
(ppERK1/2) response to [Pyr1]apelin-13 desensitized during sustained stimulation,
due to upstream APJ-specific adaptive changes. Furthermore, [Pyr1]apelin-13
stimulation caused internalization of mAPJ via clathrin coated vesicles (CCVs)
and also caused a rapid reduction in cell surface and whole cell HA-mAPJ. Our
data suggest that upon continuous agonist exposure GRK2-mediated phosphorylation
targets APJ to CCVs that are internalized from the cell surface in a beta
arrestin1-independent, EPS15- and dynamin-dependent manner. Internalization does
not appear to contribute to the desensitization of APJ-mediated ppERK1/2
activation in these cells.
PMID- 27492966
TI - Effects of thyroid hormone transporters MCT8 and MCT10 on nuclear activity of T3.
AB - Transport of thyroid hormone (TH) across the plasma membrane is necessary for the
genomic action of T3 mediated by its nuclear T3 receptor. MCT8 and MCT10 have
been identified as important TH transporters. Mutations in MCT8 result in severe
psychomotor retardation. In addition to TH transport into the cell, MCT8 and
MCT10 also facilitate TH efflux from cells. Therefore, the aim of this study was
to examine if MCT8 and MCT10 increase the availability of T3 for its nuclear
receptor rather than generate a rapid equilibrium between cellular and serum T3.
T3 action was investigated in JEG3 cells co-transfected with TRbeta1 and a T3
response element-driven luciferase construct, and T3 metabolism was analyzed in
cells transfected with type 3 deiodinase (D3). In addition, cells were
transfected with MCT8 or MCT10 and/or the cytoplasmic T3-binding protein mu
crystallin (CRYM). Luciferase signal was markedly stimulated by incubating cells
for 24 h with 1 nM T3, but this response was not augmented by MCT8 or MCT10
expression. Limiting the time of T3 exposure to 1-6 h and co-transfection with
CRYM allowed for a modest increase in luciferase response to T3. In contrast, T3
metabolism by D3 was potently stimulated by MCT8 or MCT10 expression, but it was
not affected by expression of CRYM. These results suggest that MCT8 and MCT10 by
virtue of their bidirectional T3 transport have less effect on steady-state
nuclear T3 levels than on T3 levels at the cell periphery where D3 is located.
CRYM alters the dynamics of cellular TH transport but its exact function in the
cellular distribution of TH remains to be determined.
PMID- 27492968
TI - Water-Soluble Metallocene-Containing Polymers.
AB - Metallocenes are organometallic compounds with reversible redox profiles and
tunable oxidation and reduction potentials, depending on the metal and
substituents at the cyclopentadienyl rings. Metallocenes have been introduced in
macromolecules to combine the redox-activity with polymer properties. There are
many examples of such hydrophobic polymer materials, but much fewer water-soluble
examples are found scattered across the polymer literature. However, in terms of
drug delivery and other biological applications, water solubility is essential.
For this very reason, all the synthetic routes to water-soluble metallocene
containing polymers are collected and discussed here. The focus is on neutral
ferrocene- and ruthenocene-containing and charged cobaltocenium-containing
macromolecules (i.e., symmetrical sandwich complexes). The synthetic protocols,
self-assembly behavior, and other benefits of the obtained materials are
discussed.
PMID- 27492967
TI - Perinatal management: What has been learned through the network?
AB - The Eunice Kennedy Shriver National Institute of Child Health and Human
Development Neonatal Research Network (NRN) has examined the effects of various
obstetrical perinatal interventions and neonatal delivery room practices on the
newborn with particular focus on those born preterm. Studies exploring the
effects and safety of various antepartum maternal medications and the effects of
the route and timing of delivery are examined. The NRN has contributed key
studies to the evidence base for the International Liaison Committee on
Resuscitation neonatal resuscitation guidelines. These studies are reviewed
including research on timing of cord clamping, the importance of maintaining
euthermia immediately after birth, delivery room ventilation strategies, outcomes
following delivery room cardiopulmonary resuscitation, and the effects of
prolonged resuscitation efforts. In addition, the NRN's detailed outcome data at
the lowest gestational ages have greatly influenced on how providers counsel
families regarding the appropriateness of resuscitation efforts at the lowest
gestational ages.
PMID- 27492970
TI - QT interval and drug therapy (Clinical review from Drug and Therapeutics
Bulletin).
PMID- 27492969
TI - The Arabidopsis SUMO E3 Ligase AtMMS21 Dissociates the E2Fa/DPa Complex in Cell
Cycle Regulation.
AB - Development requires the proper execution and regulation of the cell cycle via
precise, conserved mechanisms. Critically, the E2F/DP complex controls the
expression of essential genes during cell cycle transitions. Here, we discovered
the molecular function of the Arabidopsis thaliana SUMO E3 ligase METHYL
METHANESULFONATE SENSITIVITY GENE21 (AtMMS21) in regulating the cell cycle via
the E2Fa/DPa pathway. DPa was identified as an AtMMS21-interacting protein and
AtMMS21 competes with E2Fa for interaction with DPa. Moreover, DPa is a substrate
for SUMOylation mediated by AtMMS21, and this SUMOylation enhances the
dissociation of the E2Fa/DPa complex. AtMMS21 also affects the subcellular
localization of E2Fa/DPa. The E2Fa/DPa target genes are upregulated in the root
of mms21-1 and mms21-1 mutants showed increased endoreplication. Overexpression
of DPa affected the root development of mms21-1, and overexpression of AtMMS21
completely recovered the abnormal phenotypes of 35S:E2Fa-DPa plants. Our results
suggest that AtMMS21 dissociates the E2Fa/DPa complex via competition and
SUMOylation in the regulation of plant cell cycle.
PMID- 27492971
TI - Ethnic Differences in Bony Hip Morphology in a Cohort of 445 Professional Male
Soccer Players.
AB - BACKGROUND: Participation in high-impact athletic activities has recently been
associated with a higher prevalence of cam deformity. Bony hip morphology has
also emerged as an important factor in the development of hip osteoarthritis.
However, it is unknown whether bony morphology differs between ethnicities in
athletes participating in high-impact sports. PURPOSE: To investigate whether the
prevalence of specific bony hip morphological abnormalities differed between
professional male soccer players of diverse ethnic backgrounds. STUDY DESIGN:
Cross-sectional study; Level of evidence, 3. METHODS: Professional male soccer
players from an entire league attending preparticipation screening were invited
to participate in this study. Ethnicity was registered, and standardized
radiographs of anteroposterior pelvic and Dunn views were obtained. Cam and
pincer deformity, and acetabular dysplasia were quantified using the alpha angle,
triangular index, and lateral center-edge angle (LCEA). Regression analyses with
generalized estimating equations were used to determine prevalence differences in
bony hip morphology. RESULTS: A total of 445 male soccer players (890 hips; mean
age +/- SD, 25 +/- 4.9 years) participated in the study, representing the
following ethnic groups: Arabic (59%), black (24%), Persian (7%), white (6%),
East Asian (2%), and other (2%). The prevalence of cam deformity (alpha angle >60
degrees ) ranged from 57.5% to 71.7% across 4 of the groups, but East Asians had
a significantly lower prevalence (18.8%; P <= .032). A large cam deformity (alpha
angle >78 degrees ) was more prevalent in white (33.3%) compared with black
soccer players (17.8%; P = .041) and was absent in East Asian players. Pincer
deformity (LCEA >40 degrees ) was uncommon (3%) in all ethnicities. The
prevalence of acetabular dysplasia (LCEA <20 degrees ) ranged from 8.0% to 16.7%,
apart from the white group, in which prevalence was only 1.9% (P = .03).
CONCLUSION: The prevalence of a cam deformity and acetabular dysplasia differed
between ethnicities in this cohort of professional male soccer players. These
findings suggest that there may be ethnic differences in both acetabular
morphology and femoral bony response to athletic load.
PMID- 27492972
TI - Twenty-Year Outcome of a Longitudinal Prospective Evaluation of Isolated
Endoscopic Anterior Cruciate Ligament Reconstruction With Patellar Tendon or
Hamstring Autograft.
AB - BACKGROUND: Long-term prospective studies of isolated endoscopic anterior
cruciate ligament (ACL) reconstruction are limited and may include confounding
factors. PURPOSE: This study aimed to compare the outcomes of isolated ACL
reconstruction using the patellar tendon (PT) autograft and the hamstring (HT)
autograft in 180 patients over 20 years. STUDY DESIGN: Cohort study; Level of
evidence, 2. METHODS: A total of 180 participants undergoing isolated ACL
reconstruction between 1993 and 1994 were prospectively recruited. Evaluation was
performed at 1, 2, 5, 7, 10, 15, and 20 years after surgery and included the
International Knee Documentation Committee (IKDC) knee ligament evaluation with
radiographic evaluation, KT-1000 arthrometer side-to-side difference, and
subjective scores. RESULTS: Over 20 years, there were 16 patients (18%) and 9
patients (10%) with an ACL graft rupture in the HT and PT groups, respectively (P
= .13). ACL graft rupture was associated with male sex (odds ratio [OR], 3.9; P =
.007), nonideal tunnel position (OR, 3.6; P = .019), and age <18 years at the
time of surgery (OR, 4.6; P = .003). The odds of a contralateral ACL rupture were
increased in patients with the PT graft compared with patients with the HT graft
(OR, 2.2; P = .02) and those aged <18 years at the time of surgery (OR, 3.4; P =
.001). The mean IKDC scores at 20-year follow-up were 86 and 89 for the PT and HT
groups, respectively (P = .18). At 20 years, 53% and 57% of the PT and HT groups
participated in strenuous or very strenuous activities (P = .55), kneeling pain
was present in 63% and 20% of the PT and HT groups (P = .018), and radiographic
osteoarthritic change was found in 61% and 41% of the PT and HT groups (P =
.008), respectively. CONCLUSION: Compared with patients who received the HT
graft, patients who received the PT graft had significantly worse outcomes with
regard to radiologically detectable osteoarthritis, kneeling pain, and
contralateral ACL injury. At 20-year follow-up, both HT and PT autografts
continued to provide good subjective outcomes and objective stability. However,
further ACL injury is common, particularly in male individuals, younger patients,
and those with tunnel malposition.
PMID- 27492973
TI - Anthelmintic Niclosamide Disrupts the Interplay of p65 and FOXM1/beta-catenin and
Eradicates Leukemia Stem Cells in Chronic Myelogenous Leukemia.
AB - PURPOSE: Leukemia stem cells (LSC), which are insensitive to tyrosine kinase
inhibitors (TKI), are an important source of TKI resistance and disease relapse
in chronic myelogenous leukemia (CML). Obstacles to eradicating LSCs include
limited understanding of the regulation network of LSCs. The current study aimed
to examine the interplay between NF-kappaB and FOXM1/beta-catenin, and the effect
of its chemical intervention on CML LSCs. EXPERIMENTAL DESIGN: The interplay
between NF-kappaB and FOXM1/beta-catenin was analyzed by reciprocal
coimmunoprecipitation (co-IP) and chromatin immunoprecipitation (ChIP) assay in
CML cells. The effect of disturbing NF-kappaB and FOXM1/beta-catenin by
niclosamide on the self-renewal capacity and survival of LSCs was evaluated in
vitro in human primary CML CD34+ cells and in vivo in CML mice. RESULTS:
Reciprocal co-IP experiments showed physical interaction of p65 and FOXM1. p65
promoted transcription of FOXM1 gene. ChIP assay revealed recruitment of p65 on
the promoter of FOXM1 gene. Conversely, FOXM1 and beta-catenin positively
regulated the nuclear translocation and transcriptional activity of NF-kappaB in
CML cells. Niclosamide disrupted the positive feedback loop between NF-kappaB and
FOXM1/beta-catenin, thereby impairing the self-renewal capacity and survival of
CML LSCs. Niclosamide decreased the long-term engraftment of human CML LSCs in
NOD-SCID IL2Rgamma chain-deficient (NOG) mice, and prolonged the survival of CML
mice. CONCLUSIONS: Interaction of p65 with FOXM1/beta-catenin is critical in CML
and its disruption by niclosamide eradicates LSCs. These findings may improve the
understanding of a self-renewal regulatory mechanism of LSCs and offer a
rationale-based approach to eliminate LSCs in CML. Clin Cancer Res; 23(3); 789
803. (c)2016 AACR.
PMID- 27492974
TI - Loss of SMAD4 Promotes Lung Metastasis of Colorectal Cancer by Accumulation of
CCR1+ Tumor-Associated Neutrophils through CCL15-CCR1 Axis.
AB - PURPOSE: We have reported loss of SMAD4 promotes expression of CCL15 from
colorectal cancer to recruit CCR1+ myeloid cells through the CCL15-CCR1 axis,
which contributes to invasion and liver metastasis. However, the molecular
mechanism of lung metastasis is yet to be elucidated. Our purpose is to determine
whether similar mechanism is involved in the lung metastasis of colorectal
cancer. EXPERIMENTAL DESIGN: In a mouse model, we examined whether SMAD4 could
affect the metastatic activity of colorectal cancer cells to the lung through the
CCL15-CCR1 axis. We immunohistochemically analyzed expression of SMAD4, CCL15,
and CCR1 with 107 clinical specimens of colorectal cancer lung metastases. We
also characterized the CCR1+ myeloid cells using several cell-type-specific
markers. RESULTS: In a mouse model, CCL15 secreted from SMAD4-deficient
colorectal cancer cells recruited CCR1+ cells, promoting their metastatic
activities to the lung. Immunohistochemical analysis of lung metastases from
colorectal cancer patients revealed that CCL15 expression was significantly
correlated with loss of SMAD4, and that CCL15-positive metastases recruited
approximately 1.9 times more numbers of CCR1+ cells than CCL15-negative
metastases. Importantly, patients with CCL15-positive metastases showed a
significantly shorter relapse-free survival (RFS) than those with CCL15-negative
metastases, and multivariate analysis indicated that CCL15 expression was an
independent predictor of shorter RFS. Immunofluorescent staining showed that most
CCR1+ cells around lung metastases were tumor-associated neutrophil, although a
minor fraction was granulocytic myeloid-derived suppressor cell. CONCLUSIONS:
CCL15-CCR1 axis may be a therapeutic target to prevent colorectal cancer lung
metastasis. CCL15 can be a biomarker indicating poor prognosis of colorectal
cancer patients with lung metastases. Clin Cancer Res; 23(3); 833-44. (c)2016
AACR.
PMID- 27492975
TI - Effect of consumption of chicory inulin on bowel function in healthy subjects
with constipation: a randomized, double-blind, placebo-controlled trial.
AB - : Constipation is among the most common health impairments in Western countries.
This study aimed to determine the effect of the chicory-derived fermentable
dietary fiber Orafti(r) Inulin on stool frequency in healthy subjects with
constipation. The study was conducted according to recent guidance documents for
investigating bowel function and used a randomized, double-blind, placebo
controlled, cross-over design with a 2-week wash-out phase. Each study period
comprised a run-in phase followed by 4 weeks daily intake of 3 * 4g inulin or
maltodextrin (placebo). Forty-four healthy volunteers with constipation
documented stool frequency and consistency, gastrointestinal characteristics and
quality of life. Consumption of Orafti(r) Inulin significantly increased stool
frequency compared to placebo (median 4.0 [IQR 2.5-4.5] versus 3.0 [IQR 2.5-4.0]
stools/week, p = 0.038). This was accompanied by a softening of stools and trend
toward higher satisfaction versus placebo (p = 0.059). In conclusion, Orafti(r)
Inulin was effective in volunteers with chronic constipation and significantly
improved bowel function. CLINICAL TRIAL REGISTRATION: This trial was registered
at clinicaltrials.gov as NCT02548247.
PMID- 27492977
TI - Mutagenic induction of an ultra-fast water-chain proton wire.
AB - Replacement of the hydroxyl group of a hydrophilic sidechain by an H atom in the
proton wire of GFP induces formation of a water-chain proton wire. Surprisingly,
this "non-native" water chain functions as a proton wire with response times
within 10 ps of the wild type protein. This remarkable rate retention is
understood as a natural consequence of the well-known Grotthuss mechanism of
proton transfer in water.
PMID- 27492976
TI - Lectin inhibits antigen-antibody reaction in a glycoform-specific manner:
Application for detecting alpha2,6sialylated-carcinoembryonic antigen.
AB - Carcinoembryonic antigen (CEA) is a glycoprotein marker, which is widely used for
diagnosing various cancers, especially colon adenocarcinoma. In addition, CEA
mediates homotypic adhesion of colon adenocarcinoma cells, which appears to favor
hematogenous metastasis. CEA carries alpha2,6sialyl residues on its N-glycans
whereas a normal counterpart, normal fecal antigen-2, does alpha2,3sialyl
residues, suggesting that cancer-specific alpha2,6sialylation on CEA may play a
role for cell invasion and metastasis. A simple and rapid estimation of
alpha2,6sialyled CEA in detergent extracts from formalin-fixed colon
adenocarcinoma by "lectin inhibition" is reported. In the lectin inhibition
method, Sambucus sieboldiana Agglutinin (SSA) lectin, an alpha2,6sialic acid
binder, was used as a glycoform-specific inhibitor for antigen-antibody reaction
in ELISA. Detergent extracts from colon adenocarcinoma showed a fair amount of
ELISA signal in the absence of SSA whereas the signal was markedly reduced
(45~74%) in the presence of SSA, suggesting that the extracts contains
alpha2,6sialyled CEA. The presence of alpha2,6sialyled CEA in the extracts was
confirmed by lectin microarray, in which SSA, Sambucus nigra agglutinin, and
Trichosanthes japonica agglutinin I lectins were used as alpha2,6sialyl binders.
Thus lectin inhibition is a simple and rapid method for detecting
alpha2,6sialyled CEA even in crude detergent extracts from formalin-fixed
adenocarcinoma tissue.
PMID- 27492978
TI - Satisfaction Levels and Factors Influencing Satisfaction With Use of a Social App
for Neonatal and Pediatric Patient Transfer Information Systems: A Questionnaire
Study Among Doctors.
AB - BACKGROUND: The treatment of neonatal and pediatric patients is limited to
certain medical institutions depending on treatment difficulty. Effective patient
transfers are necessary in situations where there are limited medical resources.
In South Korea, the government has made a considerable effort to establish
patient transfer systems using various means, such as websites, telephone, and so
forth. However, in reality, the effort has not yet been effective. OBJECTIVE: In
this study, we ran a patient transfer information system using a social app for
effective patient transfer. We analyzed the results, satisfaction levels, and the
factors influencing satisfaction. METHODS: Naver Band is a social app and mobile
community application which in Korea is more popular than Facebook. It
facilitates group communication. Using Naver Band, two systems were created: one
by the Neonatal Intensive Care Unit and the other by the Department of Pediatrics
at Chonbuk National University Children's Hospital, South Korea. The information
necessary for patient transfers was provided to participating obstetricians
(n=51) and pediatricians (n=90). We conducted a survey to evaluate the systems
and reviewed the results retrospectively. RESULTS: The number of patients
transferred was reported to increase by 65% (26/40) obstetricians and 40% (23/57)
pediatricians. The time taken for transfers was reported to decrease by 72%
(29/40) obstetricians and 59% (34/57) pediatricians. Satisfaction was indicated
by 83% (33/40) obstetricians and 89% (51/57) pediatricians. Regarding factors
influencing satisfaction, the obstetricians reported communication with doctors
in charge (P=.03) and time reduction during transfers (P=.02), whereas the
pediatricians indicated review of the diagnosis and treatment of transferred
patients (P=.01) and the time reduction during transfers (P=.007). CONCLUSIONS:
The users were highly satisfied and different users indicated different factors
of satisfaction. This finding implies that users' requirements should be
accommodated in future developments of patient transfer information systems.
PMID- 27492979
TI - Human papillomavirus (HPV): making the case for 'Immunisation for All'.
AB - Human papillomavirus (HPV) contributes to the most common sexually transmitted
infections, with repeated and persistent infection with particular types causing
disease in both men and women. Infection with low-risk HPV types can lead to
genital warts and benign lesions of the oral cavity, while high-risk types can
cause various HPV-related malignancies. The incidence of head and neck cancers
has been rising in the past number of decades mostly due to oropharyngeal cancer
linked to HPV infection. HPV vaccination has been shown to be effective for
cervical and other anogenital HPV-related cancers, and there is significant
potential for HPV vaccination to prevent oropharyngeal cancers, given that the
HPV types implicated in this disease can be protected against by the HPV vaccine.
Few countries have implemented a universal HPV vaccination programme for males
and females, with many countries arguing that female-only vaccination programmes
protect males via herd immunity and that men who have sex with men will be
protected via targeted vaccination programmes. We argue these may be limited in
their effectiveness. We propose that the most effective, practical, ethical and
potentially cost-effective solution is universal HPV vaccination that might lead
to control of HPV-related diseases in men and women alike.
PMID- 27492980
TI - Complement C3a predicts outcome in cardiac resynchronization therapy of heart
failure.
AB - BACKGROUND: The chronic inflammation plays an important role in heart failure and
complement components might be useful markers of the prognosis. We set out to
evaluate their predictive value in the clinical outcomes of patients with cardiac
resynchronization therapy (CRT). METHODS: We determined the complement levels C3,
C3a, sC5b-9 and also the N-terminus of the prohormone brain natriuretic peptide
(NT-proBNP) of 126 heart failure patients in a prospective, single-center
observational study before and 6 months after CRT implantation. RESULTS: CRT
reduced the C3a [212.5 (148.2-283.6) vs. 153 (119.8-218.3) ng/mL, p < 0.0001] and
the sC5b-9 levels [296.9 (234.2-358.8) vs. 255.1 (210.1-319.0) ng/mL, p =
0.0006], but not the total C3 levels [1.43 (1.26-1.61) vs. 1.38 (1.23-1.57) g/L,
p = 0.57]. C3a predicted the 5-year mortality of the patients [C3a > 165 ng/mL
hazard ratio = 4.21 (1.65-10.72), p = 0.003] independent of the NT-proBNP and
other factors. After reclassification, we observed a significant net
reclassification improvement [NRI = 0.71 (0.43-0.98), p < 0.0001] and integrated
discrimination improvement [IDI = 0.08 (0.03-0.12), p = 0.0002]. CONCLUSIONS: In
patients with CRT, elevated C3a levels increase the risk of mortality independent
of the NT-proBNP levels or other factors. CRT exerts anti-inflammatory effect by
reducing the complement activation.
PMID- 27492981
TI - Breastfeeding Support in Spanish Neonatal Intensive Care Units and the Baby
Friendly Hospital Initiative.
AB - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI) has a positive effect on
breastfeeding in maternity wards; however, few studies have examined to what
degree it affects care in neonatal intensive care units (NICUs). Recently, the
BFHI has been adapted to the NICUs (Neo-BFHI). OBJECTIVE: This study aimed to
compare breastfeeding support in Spanish NICUs in hospitals with BFHI
accreditation or in the process of being accredited (group 1) with NICUs in
hospitals that have not yet begun this initiative (group 2). METHODS: A validated
questionnaire on breastfeeding support was distributed to level II and III NICUs
in Spanish public hospitals. A univariate analysis and an analysis adjusted for
the number of beds in NICUs were conducted. The results of the analysis of 36
breastfeeding support measures are presented in accordance with the Ten Steps to
Successful Breastfeeding adapted to NICUs. RESULTS: Of the 141 participating
NICUs, 129 (91%) responded to the questionnaire: 38 NICUs from group 1 and 91
NICUs from group 2. Group 1 had implemented a higher number of breastfeeding
support measures than group 2. There were significant differences in 18 measures
related to steps 2, 4, 5, 7, and 8 of the Neo-BFHI. In addition, a comparison of
NICUs in hospitals with full accreditation (7 of 129) with those in group 2
revealed significant differences in 7 measures pertaining to steps 2, 5, 8, and
9. CONCLUSION: The Spanish NICUs in hospitals with BFHI accreditation or in the
process of being accredited have better implementation of practices to promote
and support breastfeeding.
PMID- 27492982
TI - Developmental programmed cell death during asymmetric microsporogenesis in
holocentric species of Rhynchospora (Cyperaceae).
AB - Members of the Cyperaceae family exhibit an asymmetric microsporogenesis that
results in the degeneration of three out of four meiotic products. Efforts have
been made previously to describe the resulting structure, named the pseudomonad,
but mechanisms concerning the establishment of cell domains, nuclear development,
and programmed cell death are largely unknown. Using the Rhynchospora genus as a
model, evidence for cell asymmetry, cytoplasmic isolation, and programmed cell
death was obtained by a combination of electron microscopic, cytochemical,
immunocytochemical, in situ hybridization, and flow cytometric methods.
Degenerative cells were identified at the abaxial region, with the cytoskeleton
marking their delimitation from the functional domain after meiosis. After
attempting to initiate cell division with an unreplicated genome and abnormal
spindle assembly, these cells exhibited a gradual process of cytoplasmic
contraction associated with hypermethylation of cytosines and differential loss
of DNA. These results indicate that the asymmetric tetrad establishes a
functional cell, where one nucleus is preferentially selected to survive.
Degenerative haploid cells are then eliminated in a multistep process associated
with mitotic disorder, non-random elimination of repetitive DNA, vacuolar cell
death, and DNA fragmentation.
PMID- 27492983
TI - Virtual evaluation for CAD-CAM-fabricated complete dentures.
AB - New treatment concepts for complete denture fabrication, including digital
components, may increase the predictability of the treatment outcome. The reduced
number of appointments, improved biocompatibility of the materials, opportunity
to copy the outline of existing dentures, possibility of a virtual evaluation,
and reduction of costs have changed the treatment workflow considerably. This
becomes even more important against the background of an aging population. The
innovative approach presented describes the combination of an impression-occlusal
rim with a 3-dimesional face scan that allows a virtual evaluation, which might
complement or even replace the traditional evaluation of a conventional tooth
arrangement.
PMID- 27492984
TI - Effect of incorporating seed oils on the antifungal property, surface roughness,
wettability, weight change, and glucose sorption of a soft liner.
AB - STATEMENT OF PROBLEM: The colonization of Candida albicans on soft liners causes
the deterioration of material surface properties and denture stomatitis. PURPOSE:
The purpose of this in vitro study was to investigate the effect of incorporating
seed oil on the antifungal properties, surface roughness, wettability, weight
changes, and glucose adsorption/absorption of a soft liner. MATERIAL AND METHODS:
Centratherum anthelminticum, Ocimum sanctum Linn, and Linum usitatissimum seed
oils were incorporated into a soft liner, and the diameter of the inhibition zone
(DIZ) was calculated relative to the growth of C albicans at 24, 48, and 72 hours
and 7 days. The effect of incorporating oil on wettability was evaluated with the
contact angle analyzer, and effect on surface roughness was evaluated with
scanning electron microscopy. Weight changes and absorption/adsorption of glucose
to the soft liner were estimated. Data were analyzed by using paired Student t
tests and 2-way ANOVA (alpha=.01). RESULTS: Soft liner with 800 MUL each of C
anthelminticum and O sanctum oils showed complete inhibition at 72 hours; the DIZ
on day 7 were 31.66 +/-1.20 mm and 29.66 +/-1.46 mm, respectively. The change in
weight between time intervals differed significantly between conditions (P<.01).
The addition of oils decreased the surface roughness and improved wettability
significantly for O sanctum and C anthelminticum specimens (P<.01). At 72 hours,
5.5 mg of glucose was detected in the positive control, whereas no glucose was
detected in the oil specimens. CONCLUSIONS: The addition of the seed oils of C
anthelminticum and O sanctum to the soft liner significantly reduced the growth
of C albicans, improved wettability, reduced surface roughness, and minimized the
absorption and adsorption of glucose.
PMID- 27492985
TI - Accuracy of torque-limiting devices: A comparative evaluation.
AB - STATEMENT OF PROBLEM: To prevent the loosening of implant screws, clinicians
should be aware of the output torque values needed to achieve the desired
preload. Accurate torque-control devices are crucial in this regard; however,
little information is currently available comparing the accuracy of mechanical
with that of electronic torque-control devices. PURPOSE: The purpose of this in
vitro study was to identify and compare the accuracy of different types of torque
control devices. MATERIAL AND METHODS: Devices from 5 different dental implant
manufacturers were evaluated, including 2 spring-type (Straumann, Implance)
mechanical devices (MTLD), 2 friction-type (Biohorizons, Dyna) MTLDs, and 1
(Megagen) electronic torque-control device (ETLD). For each manufacturer, 5
devices were tested 5 times with a digital torque tester, and the average for
each device was calculated and recorded. The percentage of absolute deviations
from the target torque values (PERDEV) were calculated and compared by using 1
way ANOVA. A 1-sample t test was used to evaluate the ability of each device to
achieve its target torque value within a 95% confidence interval for the true
population mean of measured values (alpha=.05 for all statistical analyses).
RESULTS: One-way ANOVAs revealed statistically significant differences among
torque-control devices (P<.001). ETLD showed higher PERDEVs (28.33 +/-9.53) than
MTLDs (P<.05), whereas PERDEVS of friction-type (7.56 +/-3.64) and spring-type
(10.85 +/-4.11) MTLDs did not differ significantly. In addition, devices produced
by Megagen had a significantly higher (P<.05) PERDEV (28.33 +/-9.53) other
devices, whereas no differences were found in devices manufactured by Biohorizons
(7.31 +/-5.34), Dyna (7.82 +/-1.08), Implance (8.43 +/-4.77), and Straumann
(13.26 +/-0.79). However, 1-sample t tests showed none of the torque-control
devices evaluated in this study were capable of achieving their target torque
values (P<.05). CONCLUSIONS: Within the limitations of this in vitro study, MTLDs
were shown to be significantly more accurate than ETLDs. However, none of the
torque-control devices evaluated were able to meet their target torque values
successfully.
PMID- 27492986
TI - Percutaneous implant retention of a nasal prosthesis.
AB - This report describes an approach to the simultaneous retention of a nasal
prosthesis and an intraoral prosthesis for a patient who had undergone a total
rhinectomy with resection of the upper lip and premaxilla. At the time of the
nasal resection, 2 dental implants were placed adjacent to the resection margins
in the first premolar positions. These were used to anchor an intraoral, milled
titanium bar and overdenture to replace the missing anterior teeth and provide
support for the upper lip, which had been reconstructed with a vascularized
radial forearm free-flap. The titanium bar also incorporated a connection for a
tissue-penetrating percutaneous nasal extension, which pierced the radial forearm
flap near the junction with the hard palate. Magnetic attachments screwed to the
nasal extension retained a nasal prosthesis. The predictable and straightforward
implementation of this novel concept with digital design and manufacture of the
titanium components and guided placement of the nasal extension was made possible
with software planning.
PMID- 27492987
TI - Oral rehabilitation of patients with Chediak-Higashi syndrome using zygoma and
root form implant-supported fixed prostheses: A report of two patients.
AB - Chediak-Higashi syndrome (CH-S) is a rare genetic immunodeficiency disorder.
Fewer than 500 individuals with CH-S have been reported worldwide in the past 20
years. The dental management of patients in whom CH-S has been diagnosed has been
rarely reported and only in the form of a case report. All reports addressed the
severe periodontal disease found in those patients, and most studies concluded
that periodontal treatment had an unfavorable prognosis. As a result, complete
edentulism at an early age because of severe periodontal disease is expected. The
purpose of this report was to present 2 patients with CH-S seeking oral
rehabilitation after early tooth loss and severe bone resorption as a
manifestation of severe periodontal disease. The treatment used bilateral zygoma
implants and an all-on-4 concept. The complications encountered and management
with a 5-year post-surgery follow-up are also presented.
PMID- 27492988
TI - Clinical guidelines and procedures for provision of mandibular overdentures on 4
mini-dental implants.
AB - This article describes the flapless placement of mini-dental implants (MDI) to
retain mandibular overdentures. Clinical inclusion/exclusion criteria and
clinical protocols for the flapless placement of MDIs and for retrofitting the
overdenture are presented. A minimum bone height of 13 mm and a minimal flap are
recommended. After drilling, the 4 implants are placed with a self-tapping
process. A minimum of 15 Ncm of resistance upon final insertion indicates that
immediate loading can be performed. The metal housings with O-rings are
incorporated into the prosthesis using autopolymerizing resin. The technique and
protocol for immediately loaded 4-mini-implant mandibular overdentures is
minimally invasive and cost effective.
PMID- 27492989
TI - WITHDRAWN: Comments regarding: Janyavula S, Lawson N, Cakir D, Beck P, Ramp LC,
Burgess JO. The wear of polished and glazed zirconia against enamel. J Prosthet
Dent 2013;109:22-9.
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
http://www.elsevier.com/locate/withdrawalpolicy.
PMID- 27492990
TI - Computer-guided implant planning using a preexisting removable partial dental
prosthesis.
AB - Converting a conventional removable partial dental prosthesis (RPDP) into an
implant-assisted removable partial dental prosthesis (IARPDP) may be facilitated
by using data from the intaglio surface of the RPDP for proper implant placement.
This procedure can be done by connecting the data from the intaglio surface of
the RPDP to the residual ridge data of the cone beam computed tomography scan
with implant planning software. However, although a misplaced implant under an
RPDP can cause various complications, as yet, no technique has connected the
information on a patient's existing RPDP to the implant planning software. This
article presents computer-guided implant planning, using a patient's existing
RPDP.
PMID- 27492991
TI - Abdominal aortic aneurysm repair in New Zealand: a validation of the Australasian
Vascular Audit.
AB - BACKGROUND: In New Zealand (NZ), there are two major sources of operative data
for abdominal aortic aneurysm (AAA) repair: the Australasian Vascular Audit (AVA)
and the National Minimum Data Set (NMDS). Since the introduction of the AVA in
NZ, there has not been any attempt at the validation of outcome data. The aims of
this study were to report the outcomes of AAA repair and validate the AAA data
captured by AVA using the NMDS. METHODS: AAA procedures performed in NZ from
January 2010 to December 2014 were extracted from the AVA and NMDS. Patients
identified from the AVA had their survival status matched to the NMDS. Only
primary AAA procedures were included for the analysis, with re-interventions and
graft infections excluded. Demographical, risk factors and outcome data were used
for validation. RESULTS: The number of patients undergoing primary AAA procedure
from AVA and NMDS was 1713 and 2078, respectively. The AVA inpatient mortality
for elective and rupture AAA was 1.6 and 32.2%, respectively. The NMDS 30-day
mortality from AAA was 2.5 and 31.5%. Overall, 1604 patients were available for
matching, and the NMDS correctly reported 98.1% of endovascular aneurysm repair
and 94.2% of elective AAA repairs; however, there were major differences in
comorbidity reporting between the data sets. CONCLUSION: Both data sets were
incomplete, but combining administrative (NMDS) and clinical (AVA) data sets
provided a more accurate assessment of mortality figures. More than 80% of AAA
repairs are captured by AVA, but further work to improve compliance and
comorbidity documentation is required.
PMID- 27492992
TI - Protocols for treating patients with end-stage renal disease: a survey of
AEGD/GPR dental residencies.
AB - RATIONALE/BACKGROUND: Approximately 14% of Americans are living with chronic
kidney disease (CKD). The prevalence of end stage renal disease (ESRD), the
result of progressing CKD continues to rise by 21,000 per year.Currently the only
antibiotic prophylaxis guidelines for patients with end-stage renal disease
undergoing dental treatment were published by the AHA in 2003. Presented in three
parts, the first part of this study found no consistent protocols amongst U.S.
dental schools. The goal of the second part of the project was to determine the
current protocol being used to treat ESRD patients at accredited U.S. AEGD and
GPR programs. METHODS AND MATERIALS: A 20 multiple choice question survey was e
mailed to 262 directors of AEGDs and GPRs within the United States regarding
renal treatment protocol details and antibiotic prophylaxis for patients with
renal disease. RESULTS: 34% of respondents reported having an established renal
treatment protocol. For programs with a protocol, 65.5% of programs reported
following AHA guidelines. CONCLUSION: There is a lack of consistent, established
protocols amongst U.S. AEGD and GPR programs. It is suggested that updated and
evidence based guidelines for the safe treatment of patients be developed.
PMID- 27492993
TI - Specific locations of linear furrows in patients with esophageal eosinophilia.
AB - BACKGROUND AND AIM: Linear furrows are the most frequently found endoscopic
abnormality in patients with esophageal eosinophilia (EE); however, the precise
endoscopic features remain to be fully elucidated. Here, we aimed to clarify the
endoscopic features of EE, essential for the diagnosis of eosinophilic
esophagitis (EoE), by focusing on the specific locations of linear furrows in a
Japanese population. METHODS: We enrolled 70 cases with EE (>=15 eosinophils/high
power field) who were diagnosed at our hospital and related facilities.
Information regarding endoscopic findings and clinical parameters was
retrospectively reviewed. Next, the position of linear furrows in relation to
esophageal longitudinal folds (ridge or valley) was evaluated in each case and
compared with the position of mucosal breaks in patients with reflux esophagitis.
Finally, the relationship between linear furrows and eosinophilic infiltration
was evaluated. RESULTS: Of the 70 EE patients, 63 (90%) had linear furrows. Those
occurred in a radial pattern and were widespread throughout the lower to upper
esophagus, and exclusively found in esophageal longitudinal mucosal fold valleys,
not on ridges, which was different from the position of mucosal breaks in
patients with reflux esophagitis. Increased eosinophilic infiltration was
significantly more frequent in linear furrows in the valleys (93%) as compared to
mucosa on adjacent ridges (60%) (P < 0.05). CONCLUSION: Investigation of these
endoscopic characteristics, especially by focusing on linear furrows in
esophageal mucosal fold valleys, may provide important clues for more accurate
diagnosis of EoE.
PMID- 27492994
TI - Reference intervals for transthoracic echocardiography in the English springer
spaniel: a prospective, longitudinal study.
AB - OBJECTIVES: To establish transthoracic echocardiographic reference intervals in
adult English springer spaniel dogs. METHODS: Forty-two healthy adult English
springer spaniels were prospectively recruited from a general practice population
in the UK. Animals were examined twice, at least 12 months apart, to exclude dogs
with progressive cardiac disease. Reference intervals were calculated using Box
Cox transformations and specific variables were depicted within an expert
consensus range. Relationships of body mass, age and heart rate with cardiac
structure and function were examined and functional assessments were compared
with previous reports. Reference intervals were compared against published
ratiometric indices and allometric scaling models. RESULTS: Thirty-nine dogs
contributed to create the reference intervals. Significant relationships with
bodyweight, age and heart rate were detected, although low coefficients of
determination were found. Fractional shortening values were lower than has been
reported in many breeds but Simpson-derived ejection fractions were similar to
previously published breed-specific values. CLINICAL SIGNIFICANCE: Breed-specific
reference intervals are reported allowing for more appropriate interpretation of
echocardiographic assessments in the English springer spaniel.
PMID- 27492995
TI - EPG Recordings Reveal Differential Feeding Behaviors in Sogatella furcifera in
Response to Plant Virus Infection and Transmission Success.
AB - Plant viruses are primarily transmitted by insect vectors and virus infection may
influence on the vectors' feeding behaviors. Using an electrical penetration
graph, we detected that infection with the Southern rice black-streaked dwarf
virus (SRBSDV) in the white-backed planthopper (WBPH) and in rice plants both
altered the vector's feeding behavior. When viruliferous WBPH (carrying SRBSDV)
were fed on uninfected plants, they spent more time in salivation and phloem sap
ingestion than non-viruliferous insects. In comparison with uninfected plants,
infected plants showed an arrestant effect on non-viruliferous WBPH for phloem
sap ingestion. Differential feeding behaviors were also detected between the WBPH
that inoculated or acquired SRBSDV and those that failed to. The WBPH that
inoculated SRBSDV exhibited more probing bouts, salivation events and phloem sap
ingestion events and longer salivation than those that failed to. The WBPH that
acquired SRBSDV were quicker to reach phloem and spent more time in phloem sap
ingestion than those that failed to. These behavior alterations in the vector may
have adaptive advantages for SRBSDV transmission and spread success because
greater salivation by viruliferous vectors on uninfected hosts will promote virus
inoculation, whereas more sap ingestion by non-viruliferous vectors on infected
hosts will promote virus acquisition.
PMID- 27492996
TI - [Cardiac amyloidosis: How to recognize them and manage them?]
AB - Cardiac amyloidosis must be suspected in all cases of hypertrophic cardiomyopathy
with preserved left ventricular ejection fraction to allow specific management.
Final diagnosis needs pathological evidence, but bone scintigraphy may be an
alternative for TTR amyloidosis. Invasive samplings are limited by new tools.
Amyloidosis typing is required to start specific therapies if possible. Main
specific treatments that are available are chemotherapy for AL; transthyretin
stabilizer or gene therapy, studied for TTR-related cardiac amyloidosis.
PMID- 27492997
TI - Low Molecular Weight Norbornadiene Derivatives for Molecular Solar-Thermal Energy
Storage.
AB - Molecular solar-thermal energy storage systems are based on molecular switches
that reversibly convert solar energy into chemical energy. Herein, we report the
synthesis, characterization, and computational evaluation of a series of low
molecular weight (193-260 g mol(-1) ) norbornadiene-quadricyclane systems. The
molecules feature cyano acceptor and ethynyl-substituted aromatic donor groups,
leading to a good match with solar irradiation, quantitative photo-thermal
conversion between the norbornadiene and quadricyclane, as well as high energy
storage densities (396-629 kJ kg(-1) ). The spectroscopic properties and energy
storage capability have been further evaluated through density functional theory
calculations, which indicate that the ethynyl moiety plays a critical role in
obtaining the high oscillator strengths seen for these molecules.
PMID- 27492998
TI - Australian doctors condemn "horrific" treatment of children in juvenile
detention.
PMID- 27492999
TI - EDITORIAL.
PMID- 27493000
TI - ERRATUM.
PMID- 27493003
TI - Perinatal mental health in low- and middle-income country migrants.
PMID- 27493004
TI - The use of a self-assembled aseptic splint for minor wrist injuries.
PMID- 27493002
TI - LTbetaR controls thymic portal endothelial cells for haematopoietic progenitor
cell homing and T-cell regeneration.
AB - Continuous thymic homing of haematopoietic progenitor cells (HPCs) via the blood
is critical for normal T-cell development. However, the nature and the
differentiation programme of specialized thymic endothelial cells (ECs)
controlling this process remain poorly understood. Here using conditional gene
deficient mice, we find that lymphotoxin beta receptor (LTbetaR) directly
controls thymic ECs to guide HPC homing. Interestingly, T-cell deficiency or
conditional ablation of T-cell-engaged LTbetaR signalling results in a defect in
thymic HPC homing, suggesting the feedback regulation of thymic progenitor homing
by thymic products. Furthermore, we identify and characterize a special thymic
portal EC population with features that guide HPC homing. LTbetaR is essential
for the differentiation and homeostasis of these thymic portal ECs. Finally, we
show that LTbetaR is required for T-cell regeneration on irradiation-induced
thymic injury. Together, these results uncover a cellular and molecular pathway
that governs thymic EC differentiation for HPC homing.
PMID- 27493005
TI - Investigating the role of a poorly soluble surfactant in a thermally driven 2D
microfoam.
AB - Foam drainage dynamics is known to be strongly affected by the nature of the
surfactants stabilising the liquid/gas interface. In the present work, we
consider a 2D microfoam stabilized by both soluble (sodium dodecylsulfate) and
poorly soluble (dodecanol) surfactants. The drainage dynamics is driven by a
thermocapillary Marangoni stress at the liquid/gas interface [V. Miralles et al.,
Phys. Rev. Lett., 2014, 112, 238302] and the presence of dodecanol at the
interface induces interface stress acting against the applied thermocapillary
stress, which slows down the drainage dynamics. We define a damping parameter
that we measure as a function of the geometrical characteristics of the foam. We
compare it with predictions based on the interface rheological properties of the
solution.
PMID- 27493006
TI - Ecthyma gangrenosum in a renal transplant recipient.
PMID- 27493007
TI - The need for genetic study to diagnose some cases of distal renal tubular
acidosis.
AB - We describe the case of a young woman who was diagnosed with advanced kidney
disease, with an incidental finding of nephrocalcinosis of unknown aetiology,
having been found asymptomatic throughout her life. The genetic study by panels
of known genes associated with tubulointerstitial disease allowed us to discover
autosomal dominant distal renal tubular acidosis associated with a de novo
mutation in exon 14 of the SLC4A1 gene, which would have been impossible to
diagnose clinically due to the advanced nature of the kidney disease when it was
discovered.
PMID- 27493008
TI - Can we use structural lesions seen on MRI of the sacroiliac joints reliably for
the classification of patients according to the ASAS axial spondyloarthritis
criteria? Data from the DESIR cohort.
AB - OBJECTIVES: Investigating the utility of adding structural lesions seen on MRI of
the sacroiliac joints to the imaging criterion of the Assessment of
SpondyloArthritis (ASAS) axial SpondyloArthritis (axSpA) criteria and the utility
of replacement of radiographic sacroiliitis by structural lesions on MRI.
METHODS: Two well-calibrated readers scored MRI STIR (inflammation, MRI-SI), MRI
T1-w images (structural lesions, MRI-SI-s) and radiographs of the sacroiliac
joints (X-SI) of patients in the DEvenir des Spondyloarthrites Indifferenciees
Recentes cohort (inflammatory back pain: >=3 months, <3 years, age <50). A third
reader adjudicated MRI-SI and X-SI discrepancies. Previously proposed cut-offs
for a positive MRI-SI-s were used (based on <5% prevalence among no-SpA
patients): erosions (E) >=3, fatty lesions (FL) >=3, E/FL >=5. Patients were
classified according to the ASAS axSpA criteria using the various definitions of
MRI-SI-s. RESULTS: Of the 582 patients included in this analysis, 418 fulfilled
the ASAS axSpA criteria, of which 127 patients were modified New York (mNY)
positive and 134 and 75 were MRI-SI-s positive (E/FL>=5) for readers 1 and 2,
respectively. Agreement between mNY and MRI-SI-s (E/FL>=5) was moderate (reader
1: kappa: 0.39; reader 2: kappa: 0.44). Using the E/FL>=5 cut-off instead of mNY
classification did not change in 478 (82.1%) and 469 (80.6%) patients for readers
1 and 2, respectively. Twelve (reader 1) or ten (reader 2) patients would not be
classified as axSpA if only MRI-SI-s was performed (in the scenario of
replacement of mNY), while three (reader 1) or six (reader 2) patients would be
additionally classified as axSpA in both scenarios (replacement of mNY and
addition of MRI-SI-s). Similar results were seen for the other cut-offs (E>=3,
FL>=3). CONCLUSIONS: Structural lesions on MRI can be used reliably either as an
addition to or as a substitute for radiographs in the ASAS axSpA classification
of patients in our cohort of patients with short symptom duration.
PMID- 27493009
TI - SILAC-based quantitative proteomic analysis of secretome of Marc-145 cells
infected with porcine reproductive and respiratory syndrome virus.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative
agent of PRRS, which causes severe reproductive failure in sows, respiratory
disease in young and growing pigs, and enormous economic losses to the global
swine industry. In this study, SILAC combined with MS/MS was used to
quantitatively identify the secretory proteins differentially expressed in PRRSV
infected Marc-145 cells compared with mock-infected controls. In total, we
identified 204 secretory proteins showing significant differences in infected
cells (163 upregulated, 41 downregulated). Intensive bioinformatic analysis of
secretome data revealed that PRRSV infection strongly activated nonclassical
protein secretion, especially vesicle-mediated release of exosomal proteins,
including different danger-associated molecular pattern molecules and the
majority of secreted proteins involved in protein binding and transport,
regulation of response to stimulus, metabolic processes, and immune responses.
According to the functional proteins analysis, we speculate that proteins
functioning in binding, transport, and the immune response are exploited by PRRSV
to facilitate virus replication and immune evasion. Our study for the first time
analyzes the secretory protein profile of PRRSV-infected Marc-145 cells and
provides valuable insight into the host response to PRRSV infection.
PMID- 27493010
TI - Virulence determinants in enteroaggregative Escherichia coli from North India and
their interaction in in vitro organ culture system.
AB - Enteroaggregative Escherichia coli (EAEC) is an important diarrhoeal pathogen
causing diseases in multiple epidemiological and clinical settings. In developing
countries like India, diarrhoeal diseases are one of the major killers among
paediatric population and oddly, few studies are available from Indian paediatric
population on the variability of EAEC virulence genes. In this study, we examined
the distribution of plasmid and chromosomal-encoded virulence determinants in
EAEC isolates, and analysed cytokines response generated against EAEC with
specific aggregative adherence fimbriae (AAF) type in duodenal biopsies using in
vitro organ culture (IVOC) mimicking in vivo conditions. Different virulence
marker combinations among strains were reflected as a function of specific
adhesins signifying EAEC heterogeneity. fis gene emerged as an important genetic
marker apart from aggA and aap Further, EAEC infection in IVOC showed
upregulation of IL-8, IL-1beta, IL-6, TNF-alpha and TLR-5 expression. EAEC with
AAFII induced significant TLR-5 and IL-8 response, conceivably owing to more
pathogenicity markers. This study sheds light on the pattern of EAEC pathotypes
prevalent in North Indian paediatric population and highlights the presence of
unique virulence combinations in pathogenic strains. Thus, evident diversity in
EAEC virulence and multifaceted bacteria-host crosstalk can provide useful
insights for the strategic management of diarrhoeal diseases in India, where
diarrhoeal outbreaks are more frequent.
PMID- 27493011
TI - Aeromonas salmonicida subsp. salmonicida strains isolated from Chinese freshwater
fish contain a novel genomic island and possible regional-specific mobile genetic
elements profiles.
AB - Two strains of Aeromonas salmonicida, YK and BG, were isolated from largemouth
bronze gudgeon and northern whitefish in China, and identified as A. salmonicida
subsp. salmonicida based on phylogenetic analysis of vapA and 16S rRNA gene
sequences. YK and BG originated from freshwater fish, one of which belonged to
the cyprinid family, and the strains showed a difference in virulence.
Subsequently, we performed whole genome sequencing of the strains, and comparison
of their genomic sequences to the genome of the A449 reference strain revealed
various genomic rearrangements, including a new variant of the genomic island
AsaGEI in BG, designated as AsaGEI2c This is the first report on a GEI of A.
salmonicida strain from China. Furthermore, both YK and BG strains contained a
Tn7 transposon inserted at the same position in the chromosome. Finally, IS
dependent rearrangements on pAsa5 are deemed likely to have occurred, with
omission of the resD gene in both strains as well as omission of genes related to
the IncF conjugal transfer system in the YK isolate. This study demonstrates that
A. salmonicida subsp. salmonicida can infect non-salmonids (cyprinids) in
addition to salmonids, and that AsaGEI2c might be useful as a geographical
indicator of Chinese A. salmonicida subsp. salmonicida isolates.
PMID- 27493012
TI - Superior adsorption performance for triphenylmethane dyes on 3D architectures
assembled by ZnO nanosheets as thin as ~1.5nm.
AB - The 3-dimensional hierarchical ZnO flower-like architectures have been
synthesized in a Zn(Ac)2.2H2O-Na2SeO3-KBH4-pyridine solvothermal system at 100
degrees C for 24h. The flower-like architecture is assembled from ZnO nanosheets
with a thickness of ~1.5nm, and the flower-like architecture specific surface
area is 132m(2)/g. When the ZnO flower-like architecture is used as the adsorbent
for acid fuschin (AF), malachite green (MG), basic fuchsin (BF), congo red (CR)
and acid red (AR) in water, the adsorption capacities for AF, MG, BF, CR and AR
are 7154.9, 2587.0, 1377.9, 85.0 and 38.0mg/g, respectively. Evidently, the as
obtained ZnO flower-like architectures show excellent adsorption performances for
triphenylmethane dyes, and the adsorption capacity of 7154.9mg/g for AF is the
highest of all adsorbents for dyes. The adsorption mechanism can be attributed to
the electrostatic attraction and the formation of ion-association complex between
triphenylmethane dyes and ZnO hierarchical flower-like architectures.
PMID- 27493013
TI - The suppression effect in visuospatial and verbal working memory span tasks in
patients with Alzheimer's disease: a 2-year follow-up study.
AB - This study adapted a new task to assess visuospatial and verbal working memory
impairments in patients with Alzheimer Disease (AD), including an executive
strategy of information suppression. The aim was to examine the visuospatial and
verbal difficulties, and additionally to explore the average sex differences,
during a 2-year follow-up study. The results indicated that patients with AD
showed a significantly lower performance, compared with healthy elderly controls,
especially with the suppression of information required in this new task.
However, suppression did not lead to a significantly greater decline in the
performance of patients when compared with the control group.
PMID- 27493014
TI - The human microbiome in rheumatic autoimmune diseases: A comprehensive review.
AB - The human microbiome consists of the total diversity of microbiota and their
genes. High-throughput sequencing has allowed for inexpensive and rapid
evaluation of taxonomic representation and functional capability of the
microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases
are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be
influenced by host genetics and environmental factors. Dysbiosis is also
associated with shifts in certain functional pathways. The goal of this article
is to provide a current and comprehensive review of the unique characteristics of
the microbiome of patients with autoimmune and inflammatory rheumatic diseases,
measured using high-throughput sequencing. We also highlight the need for broader
studies utilizing a longitudinal approach to better understand how the human
microbiome contributes to disease susceptibility, and to characterize the role of
the interaction between host genetics and microbial diversity in the pathogenesis
of autoimmune diseases, disease manifestations, and progression.
PMID- 27493016
TI - Evaluation of the dose-response relationship of oral robenacoxib in urate crystal
induced acute stifle synovitis in dogs.
AB - The objective of the study was to establish the dose-response relationship for
robenacoxib, a selective cyclooxygenase (COX)-2 inhibitor, in a urate crystal
model of acute synovitis. In a randomized partial Latin square design trial, 12
beagle dogs were administered orally single doses of robenacoxib (0.5, 1, 2, 4
and 8 mg/kg), placebo and the positive control meloxicam (0.1 mg/kg), 3 h after
injection of sodium urate crystals into a stifle joint. Dogs were assessed for
weight bearing on a force plate and by subjective clinical orthopaedic
observations. Robenacoxib produced dose-dependent improvement in weight bearing,
and decreased pain on palpation and joint swelling, over the dose range 0.5-2
mg/kg with no further increase in effect over the range 2-8 mg/kg. For weight
bearing on the force plate, the ED50 of robenacoxib was 0.6-0.8 mg/kg. The onset
of action and time to peak effect of robenacoxib were faster (respectively, 2-2.5
h and 3-5 h) than for meloxicam (respectively, 3 h and 6 h). Robenacoxib
significantly inhibited COX-2 at all doses, with dose-related activity.
Robenacoxib did not inhibit COX-1 over the dose range 0.5-4 mg/kg, but produced
transient inhibition at 8 mg/kg. In conclusion, oral administration of
robenacoxib over the dose range 0.5-8 mg/kg demonstrated significant analgesic
and anti-inflammatory efficacy in dogs.
PMID- 27493015
TI - Accelerating Enzymatic Catalysis Using Vortex Fluidics.
AB - Enzymes catalyze chemical transformations with outstanding stereo- and regio
specificities, but many enzymes are limited by their long reaction times. A
general method to accelerate enzymes using pressure waves contained within thin
films is described. Each enzyme responds best to specific frequencies of pressure
waves, and an acceleration landscape for each protein is reported. A vortex
fluidic device introduces pressure waves that drive increased rate constants
(kcat ) and enzymatic efficiency (kcat /Km ). Four enzymes displayed an average
seven-fold acceleration, with deoxyribose-5-phosphate aldolase (DERA) achieving
an average 15-fold enhancement using this approach. In solving a common problem
in enzyme catalysis, a powerful, generalizable tool for enzyme acceleration has
been uncovered. This research provides new insights into previously uncontrolled
factors affecting enzyme function.
PMID- 27493017
TI - Three-Arm Branched Microporous Organic Nanotube Networks.
AB - Here, a novel method is demonstrated for the preparation of three-arm branched
microporous organic nanotube networks (TAB-MONNs) based on molecular templating
of three-arm branched core-shell bottlebrush copolymers and Friedel-Crafts
alkylation reaction. The unique three-arm branched bottlebrush copolymers are
synthesized by a combination of atom transfer radical polymerization, reversible
addition-fragmentation chain transfer polymerization, and ring-opening
polymerization techniques. In this approach, the length and diameter of branched
tube units can be well-controlled by rational molecular design. Moreover, the as
prepared TAB-MONNs possess a high surface area and exhibit a superior adsorption
capacity for Rhodamine 6G (R6G) and p-cresol.
PMID- 27493018
TI - In vitro aerodynamic characteristics of aerosol delivered from different
inhalation methods in mechanical ventilation.
AB - Aerodynamic characteristics of aerosol delivery during invasive mechanical
ventilation (IMV) are mostly determined by inserting cascade impactor in the
circuit. Impactor might have some effect on airflow within IMV. Hence, the aim of
the present study was to develop and evaluate new in vitro aerodynamic
characterization methodology without affecting airflow in IMV. Breathing
simulator was set in standard adult IMV circuit with inspiratory and expiratory
pressures of 20 and 5 cm H2O, 1:3 inspiratory-expiratory ratio, 15 breaths min-1,
and tidal volume of 500 ml. Two ml of salbutamol solution containing 10,000 MUg
was nebulized using three different vibrating mesh nebulizers (VMNs) and
Sidestream jet nebulizer (JET). Sixteen-metered doses, containing 100 MUg
salbutamol each, were delivered using three different spacers. Each device was
placed in inspiration limb of Y-piece of ventilator tubing. Aerodynamic
characteristics of aerosol delivered were measured using cooled Andersen cascade
impactor, with mixing inlet connected to it. VMNs used had significantly more
total mass in the impactor (p < .001) and fine particle dose (p < .001) compared
to JET. Spacers used had higher total mass in the impactor percent (p < .001) and
fine particle fraction compared to nebulizers. The in vitro IMV methodology
setting suggested here showed encouraging results in comparison of different
aerosol delivery systems in intubated patient.
PMID- 27493019
TI - What is the optimal duration of oral misoprostol treatment for cervical ripening?
AB - OBJECTIVES: To evaluate the number of misoprostol tablets needed to obtain a
Bishop score (BS) >= 6 or a significant cervical change (>=2 points in BS) during
cervical ripening. METHODS: Retrospective study of women with term singleton
pregnancies and a BS < 6 taking oral misoprostol (20 MUg first 2 doses followed
by 40 MUg every 2 h) for cervical ripening. RESULTS: We included 400 women, 72%
nulliparous, mean age of 31.3 +/- 5.9 years and 70% with a baseline BS <= 2.
During cervical ripening, 61 (15.3%) achieved a BS >= 6 and 205 (51.3%) a
significant change in BS. The incremental risk to achieve a BS >= 6 after 4
tablets was low (+3.25%) with an incremental probability of +12.75% for painful
uterine contractions and +0.5% for abnormal fetal tracing (AFT). The incremental
probability to achieve a significant change in BS after 7 tablets was low
(+2.0%). 24.3% women delivered by cesarean section which likelihood significantly
increased with maternal age <35 years, BMI >= 30, nulliparity, AFT, and baseline
BS <= 2. CONCLUSIONS: The marginal benefit of giving more than 7 misoprostol
tablets (14 h) during cervical ripening is very low.
PMID- 27493020
TI - The Pressure induced by salt crystallization in confinement.
AB - Salt crystallization is a major cause of weathering of rocks, artworks and
monuments. Damage can only occur if crystals continue to grow in confinement,
i.e. within the pore space of these materials, thus generating mechanical stress.
We report the direct measurement, at the microscale, of the force exerted by
growing alkali halide salt crystals while visualizing their spontaneous
nucleation and growth. The experiments reveal the crucial role of the wetting
films between the growing crystal and the confining walls for the development of
the pressure. Our results suggest that the measured force originates from
repulsion between the similarly charged confining wall and the salt crystal
separated by a ~1.5 nm liquid film. Indeed, if the walls are made hydrophobic, no
film is observed and no repulsive forces are detected. We also show that the
magnitude of the induced pressure is system specific explaining why different
salts lead to different amounts of damage to porous materials.
PMID- 27493021
TI - The preparation of Cistanche phenylethanoid glycosides liquid proliposomes:
Optimized formulation, characterization and proliposome dripping pills in vitro
and in vivo evaluation.
AB - Water-soluble Cistanche phenylethanoid glycosides (CPhGs) have poor permeability
and low bioavailability. However, liposomes can improve the permeability of such
drugs and their poor stability, and proliposomes have been used to overcome these
problems. Based on this, Cistanche phenylethanoid glycoside liquid proliposomes
(CPhGsP) and dripping(?) pills were prepared and optimized using response surface
methodology. The properties of CPhGsP were evaluated in terms of their
encapsulation efficiency, particle size, zeta potential, and morphology. The
results obtained showed that the optimal formulation was drug/soybean
phospholipid/poloxamer-188/sodium deoxycholate/propylene glycol
1:22.38:3.52:0.84:80 (w/w/w/w/v). This resulted in an encapsulation efficiency,
particle size, and zeta potential of hydrated proliposomes with phosphate buffer
solution (pH7.4) of 51.97%, 671.7nm, and -25.49mV, respectively. Stability
testing of CPhGsP and CPhGs ordinary liposomes was carried out for 3months at 4+/
2 degrees C, 25+/-2 degrees C, 40+/-2 degrees C, 75+/-5% RH. The results obtained
showed that the stability of the proliposomes was better than that of ordinary
liposomes at the same temperature, while a lower temperature of 4 degrees C is
ideal for storage. Cistanche phenylethanoid glycoside liquid proliposomes
dripping pills (CPhGsPD) are efficiently released in gastrointestinal solution as
shown by in vitro release experiments and the structure of the liposomes does not
destroy the proliposome dripping pills by hydration. In vivo experiments showed
that the areas under the plasma level-time curves and peak concentrations of
CPhGsPD and hydrated proliposomes were higher than those of CPhGs. Moreover, with
CPhGsPD, the pharmacokinetic parameters were similar to those with hydrated
proliposomes. These results showed that CPhGsPD offer a good way to improve the
oral delivery of CPhGs.
PMID- 27493022
TI - Geographic access to interventional cardiology services in one rural state.
AB - OBJECTIVES: Explore (1) the characteristics of the Maine population with delayed
geographic access to interventional cardiology (IC) services and (2) the effect
of delayed geographic IC access on coronary mortality. BACKGROUND: Acute coronary
syndrome (ACS), ST-segment elevated myocardial infarction (STEMI), and non-ST
segment elevated myocardial infarction (NSTEMI) are highly prevalent. Coronary
mortality is minimized when victims have prompt IC access. METHODS: The study
design was (1) an exploration of census data to investigate disparities in
geographic IC access and (2) a secondary analysis of administrative claims data
to investigate coronary mortality relative to delayed geographic IC access.
RESULTS: Delayed access was associated in the Maine population with rural
residence, advanced age, high school education, and lack of health insurance.
Delayed access was associated with increased unadjusted coronary mortality, but
not age-adjusted coronary mortality. CONCLUSION: Delayed geographic IC access was
associated with disparity but not with increased age-adjusted coronary mortality.
PMID- 27493023
TI - Changes in physical function after hospitalization in patients with nursing and
healthcare-associated pneumonia.
AB - To clarify the functional changes after hospitalization due to pneumonia in
elderly Japanese patients, we investigated the changes in physical functioning,
nutritional routes, and diet that occurred after hospitalization in patients with
nursing and healthcare-associated pneumonia (NHCAP). We analyzed 405 patients
with NHCAP and compared findings with 448 patients with community-acquired
pneumonia (CAP). Among the NHCAP patients, 140 (34%) patients showed a decline in
activities of daily living function between baseline and discharge. After
hospital discharge, 149 (37%) NHCAP patients did not return to the same residence
location compared with where they were living prior to hospital admission. The
frequency of this outcome was significantly higher in NHCAP patients than in CAP
patients (p < 0.0001). After 6 months' follow-up, of the patients who transferred
to different hospitals, 41 (73%) patients with CAP had returned to their own
home, but only 16 (20%) patients with NHCAP could return home (p < 0.0001). Rates
of alteration of nutritional route and type of diet from oral nutrition were
significantly higher in NHCAP patients compared with CAP patients (22% vs 4%, p <
0.0001). Our results demonstrated that approximately one-third of hospitalized
patients with NHCAP showed a decline in physical function. In addition,
approximately one-fifth of NHCAP patients had changed their route of nutrition
and type of diet. Our results indicated that physicians should attach greater
importance to preventative measures against NHCAP rather than relying on
antibiotic therapy post-infection in the management of pneumonia in elderly
patients in order to extend their healthy life expectancy.
PMID- 27493024
TI - Duration of fever and other symptoms after the inhalation of laninamivir
octanoate hydrate for influenza treatment; comparison among the four Japanese
influenza seasons from 2011-2012 to 2014-2015.
AB - The duration of fever and other symptoms as markers of the clinical effectiveness
of laninamivir octanoate hydrate (laninamivir) were investigated in the Japanese
2014-2015 influenza season and the results were compared with those of the
previous three seasons, 2011-2012 to 2013-2014. From these four seasons, the data
of 636 influenza A(H3N2) and 128 influenza B patients was available for analysis.
No significant difference was found in their baseline characteristics. The median
duration of fever for all A(H3N2) patients ranged from 32.0 to 41.0 h. The
duration of fever in the 2014-2015 season was significantly shorter than that in
the 2012-2013 and 2013-2014 seasons (p = 0.0204 and 0.0391, respectively), but
the differences were within nine hours. The median duration of symptoms for
A(H3N2) ranged from 80.0 to 89.0 h, with no significant difference among the four
seasons (p = 0.2222). The median duration of fever for B patients ranged from
43.0 to 50.0 h, with no significant difference among the four seasons. The
duration of the symptoms for B varied by season, but no significant difference
was found among the four seasons. Over the four seasons, 44 adverse events were
reported from among 921 patients, with all resolving without treatment. These
results indicate the continuing effectiveness of laninamivir against influenza
A(H3N2) and B, with no safety issues. It is unlikely that the clinical use of
laninamivir has caused viral resistance in the currently epidemic viruses.
PMID- 27493025
TI - Factors Influencing Adherence to Antiretroviral Therapy among People Living with
HIV in Coastal South India.
AB - BACKGROUND: Antiretroviral Therapy (ART) has transformed life threatening
HIV/AIDS scenario into chronic manageable disease. METHODOLOGY: In this cross
sectional, 409 People Living with Human Immunodeficiency Virus (PLHIV) aged >= 18
years, who were on ART, were assessed regarding the adherence to ART and factors
affecting adherence using semi-structured questionnaire. The association between
factors affecting adherence and the level of adherence were analyzed using
multiple logistic regression model and odds ratio (OR) with 95% confidence
intervals (CI) were reported. RESULTS: Among 409 PLHIV, 70.4% showed adherence to
ART (>=95%). Univariate analysis yielded many factor associated with adherence (P
< 0.05). However, on multivariate analysis, PLHIV who do not forget to take ART
and not consuming alcohol were the factors consistent with adherence to ART (P <
0.05). CONCLUSION: Regular patient education and counseling regarding the usage
of memory aids and abstinence from alcohol could be useful for adherence and long
term success of ART among PLHIV.
PMID- 27493026
TI - Disease modelling using human iPSCs.
PMID- 27493027
TI - Myelinosomes act as natural secretory organelles in Sertoli cells to prevent
accumulation of aggregate-prone mutant Huntingtin and CFTR.
AB - Inappropriate deposition of insoluble aggregates of proteins with abnormal
structures is a hallmark of affected organs in protein aggregation disease. Very
rare, affected organs avoid aggregation naturally. This concerns atrophic testis
in Huntington disease (HD). We aimed to understand how HD testis avoids
aggregation. Using HD model R6/1 mice, we demonstrate that affected testis
contain rare organelles myelinosomes. Myelinosomes secreted from testis somatic
TM4 Sertoli cells provide the release of aggregate-prone mutant, but not normal
Huntingtin (Htt) exon1. Myelinosomes also support the release of other aggregate
prone mutant protein responsible for cystic fibrosis (CF), F508delCFTR. The
traffic and discharge of myelinosomes is facilitated by multivesicular bodies
(MVB)s. Inhibition of MVB excretion induced reversible retention of both
misfolded proteins inside TM4 Sertoli cells. We propose that myelinosome-mediated
elimination of mutant proteins is an unusual secretory process allowing Sertoli
cells getting rid of misfolded proteins to avoid aggregation and to maintain cell
proteostasis.
PMID- 27493028
TI - Neuromuscular junctions are pathological but not denervated in two mouse models
of spinal bulbar muscular atrophy.
AB - Spinal bulbar muscular atrophy (SBMA) is a progressive, late onset neuromuscular
disease causing motor dysfunction in men. While the morphology of the
neuromuscular junction (NMJ) is typically affected by neuromuscular disease,
whether NMJs in SBMA are similarly affected by disease is not known. Such
information will shed light on whether defective NMJs might contribute to the
loss of motor function and represent a potential therapeutic target for treating
symptoms of SBMA. To address this gap in information, the morphology of NMJs was
examined in two mouse models of SBMA, a myogenic model that overexpresses
wildtype androgen receptor (AR) exclusively in muscle fibres and a knockin (KI)
model expressing a humanized mutant AR gene. The tripartite motor synapse
consisting of motor nerve terminal, terminal Schwann cells (tSCs) and
postsynaptic specialization were visualized and analysed using confocal
microscopy. Counter to expectation, we found no evidence of denervation in either
model, but junctions in both models show pathological fragmentation and an
abnormal synaptophysin distribution consistent with functionally weak synapses.
Neurofilament accumulations were observed only in the myogenic model, even though
axonal transport dysfunction is characteristic of both models. The ultrastructure
of NMJs revealed additional pathology, including deficits in docked vesicles
presynaptically, wider synaptic clefts, and simpler secondary folds
postsynaptically. The observed pathology of NMJs in diseased SBMA mice is likely
the morphological correlates of defects in synaptic function which may underlie
motor impairments associated with SBMA.
PMID- 27493029
TI - The COQ2 genotype predicts the severity of coenzyme Q10 deficiency.
AB - COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for
the second step of the final reaction sequence of Coenzyme Q10 (CoQ)
biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency
and have been associated with the widest clinical spectrum, ranging from fatal
neonatal multisystemic disease to late-onset encephalopathy. However, the reasons
of this variability are still unknown.We have characterized the structure of
human COQ2, defined its subcellular localization and developed a yeast model to
validate all the mutant alleles reported so far.Our findings show that the main
functional transcript of COQ2 is shorter than what was previously reported and
that its protein product localizes to mitochondria with the C-terminus facing the
intermembrane space. Complementation experiments in yeast showed that the
residual activity of the mutant proteins correlates with the clinical phenotypes
observed in patients.We defined the structure of COQ2 with relevant implications
for mutation screening in patients and demonstrated that, contrary to other COQ
gene defects such as ADCK3, there is a correlation between COQ2 genotype and
patient's phenotype.
PMID- 27493030
TI - New Insight in Copper-Ion Binding to Human Islet Amyloid: The Contribution of
Metal-Complex Speciation To Reveal the Polypeptide Toxicity.
AB - Type-2 diabetes (T2D) is considered to be a potential threat on a global level.
Recently, T2D has been listed as a misfolding disease, such as Alzheimer's and
Parkinson's diseases. Human islet amyloid polypeptide (hIAPP) is a molecule
cosecreted in pancreatic beta cells and represents the main constituent of an
aggregated amyloid found in individuals affected by T2D. The trace-element serum
level is significantly influenced during the development of diabetes. In
particular, the dys-homeostasis of Cu(2+) ions may adversely affect the course of
the disease. Conflicting results have been reported on the protective role played
by complex species formed by Cu(2+) ions with hIAPP or its peptide fragments in
vitro. The histidine (His) residue at position 18 represents the main binding
site for the metal ion, but contrasting results have been reported on other
residues involved in metal-ion coordination, in particular those toward the N or
C terminus. Sequences that encompass regions 17-29 and 14-22 were used to
discriminate between the two models of the hIAPP coordination mode. Due to poor
solubility in water, poly(ethylene glycol) (PEG) derivatives were synthesized. A
peptide fragment that encompasses the 17-29 region of rat amylin (rIAPP) in which
the arginine residue at position 18 was substituted by a histidine residue was
also obtained to assess that the PEG moiety does not alter the peptide secondary
structure. The complex species formed by Cu(2+) ions with Ac-PEG-hIAPP(17-29)-NH2
, Ac-rIAPP(17-29)R18H-NH2 , and Ac-PEG-hIAPP(14-22)-NH2 were studied by using
potentiometric titrations coupled with spectroscopic methods (UV/Vis, circular
dichroism, and EPR). The combined thermodynamic and spectroscopic approach
allowed us to demonstrate that hIAPP is able to bind Cu(2+) ions starting from
the His18 imidazole nitrogen atom toward the N-terminus domain. The stability
constants of copper(II) complexes with Ac-PEG-hIAPP(14-22)-NH2 were used to
simulate the different experimental conditions under which aggregate formation
and oxidative stress of hIAPP has been reported. Speciation unveils: 1) the
protective role played by increased amounts of Cu(2+) ions on the hIAPP
fibrillary aggregation, 2) the effect of adventitious trace amounts of Cu(2+)
ions present in phosphate-buffered saline (PBS), and 3) a reducing fluorogenic
probe on H2 O2 production attributed to the polypeptide alone.
PMID- 27493031
TI - Sustainable Pathways to Pyrroles through Iron-Catalyzed N-Heterocyclization from
Unsaturated Diols and Primary Amines.
AB - Pyrroles are prominent scaffolds in pharmaceutically active compounds and play an
important role in medicinal chemistry. Therefore, the development of new, atom
economic, and sustainable catalytic strategies to obtain these moieties is highly
desired. Direct catalytic pathways that utilize readily available alcohol
substrates have been recently established; however, these approaches rely on the
use of noble metals such as ruthenium or iridium. Here, we report on the direct
synthesis of pyrroles using a catalyst based on the earth-abundant and
inexpensive iron. The method uses 2-butyne-1,4-diol or 2-butene-1,4-diol that can
be directly coupled with anilines, benzyl amines, and aliphatic amines to obtain
a variety of N-substituted pyrroles in moderate-to-excellent isolated yields.
PMID- 27493032
TI - Confocal Raman Microscopy of Hybrid-Supported Phospholipid Bilayers within
Individual C18-Functionalized Chromatographic Particles.
AB - Measuring lipid-membrane partitioning of small molecules is critical to
predicting bioavailability and investigating molecule-membrane interactions. A
stable model membrane for such studies has been developed through assembly of a
phospholipid monolayer on n-alkane-modified surfaces. These hybrid bilayers have
recently been generated within n-alkyl-chain (C18)-modified porous silica and
used in chromatographic retention studies of small molecules. Despite their
successful application, determining the structure of hybrid bilayers within
chromatographic silica is challenging because they reside at buried interfaces
within the porous structure. In this work, we employ confocal Raman microscopy to
investigate the formation and temperature-dependent structure of hybrid
phospholipid bilayers in C18-modified, porous-silica chromatographic particles.
Porous silica provides sufficient surface area within a confocal probe volume
centered in an individual particle to readily measure, with Raman microscopy, the
formation of an ordered hybrid bilayer of 1,2-dimyristoyl-sn-glycero-3
phosphocholine (DMPC) with the surface C18 chains. The DMPC surface density was
quantified from the relative Raman scattering intensities of C18 and phospholipid
acyl chains and found to be ~40% of a DMPC vesicle membrane. By monitoring Raman
spectra acquired versus temperature, the bilayer main phase transition was
observed to be broadened and shifted to higher temperature compared to a DMPC
vesicle, in agreement with differential scanning calorimetry (DSC) results. Raman
scattering of deuterated phospholipid was resolved from protonated C18 chain
scattering, showing that the lipid acyl and C18 chains melt simultaneously in a
single phase transition. The surface density of lipid in the hybrid bilayer, the
ordering of both C18 and lipid acyl chains upon bilayer formation, and decoupling
of C18 methylene C-H vibrations by deuterated lipid acyl chains all suggest an
interdigitated acyl chain structure. The simultaneous melting of both layers is
also consistent with an interdigitated structure, where immobility of surface
grafted C18 chains decreases the cooperativity and increases the melting
temperature compared to a vesicle bilayer.
PMID- 27493039
TI - Serological survey finds evidence of bluetongue antibodies in UK cattle.
PMID- 27493040
TI - 'Remarkable' horse awarded PDSA Dickin Medal.
PMID- 27493044
TI - Animals pushed to their limits: what are the implications for welfare?
AB - From working horses to dairy cows to dogs, animals are being pushed to their
biological limits. But how far can we go before their health and welfare is
compromised? This was one of the questions discussed at a recent meeting
organised jointly by CABI and the Royal Veterinary College. Georgina Mills
reports.
PMID- 27493045
TI - Veterinary medicines update.
AB - The following information has been produced for Veterinary Record by the
Veterinary Medicines Directorate (VMD) to provide an update for veterinary
surgeons on recent changes to marketing authorisations for veterinary medicines
in the UK and on other relevant issues.
PMID- 27493046
TI - Disease surveillance in England and Wales, July 2016.
AB - ? Current and emerging issues? Highlights from the scanning surveillance network?
Update on international disease threats? Botulism outbreaks in wild
waterbirdsThese are among matters discussed in the Animal and Plant Health
Agency's (APHA's) July disease surveillance report.
PMID- 27493047
TI - Suspected avian botulism outbreaks in wild waterbirds during the summer.
AB - The APHA Wildlife Expert Group reports on disease identified by the APHA Diseases
of Wildlife Scheme and Avian Influenza Wild Bird Surveillance project.
PMID- 27493048
TI - Does it matter that more boys aren't applying to vet school?
PMID- 27493049
TI - Microchipping very small dogs.
PMID- 27493050
TI - Measuring health-related quality of life in companion animals.
PMID- 27493051
TI - Haemorrhagic bowel syndrome associated with ingestion of spoiled concentrate in
two Brown Swiss cows.
PMID- 27493052
TI - Increasing remission in diabetic cats.
PMID- 27493060
TI - Working in industry using skills learned in practice.
AB - After qualifying, Blaise Scott-Morris enjoyed working in small animal practice.
In search of a new challenge, she joined Virbac where she is a technical adviser.
PMID- 27493061
TI - Diary of a parliamentary intern.
AB - With Brexit dominating the headlines, parliamentary intern Anthony Ridge
considers some future implications for vets.
PMID- 27493062
TI - Arthritis is developed in Borrelia-primed and -infected mice deficient of
interleukin-17.
AB - Interleukin-17 (IL-17) has been shown to participate in the development of Lyme
arthritis in experimental mice. For example, neutralization of IL-17 with
antibodies inhibits induction of arthritis in Borrelia-primed and -infected
C57BL/6 wild-type mice. We hypothesized that mice lacking IL-17 would fail to
develop Borrelia-induced arthritis. IL-17-deficient and wild-type C57BL/6 mice
were primed with heat-inactivated Borrelia and then infected with viable
spirochetes 3 weeks later. No swelling or major histopathological changes of the
hind paws were detected in IL-17-deficient or wild-type mice that were primed
with Borrelia or infected with viable spirochetes. By contrast, IL-17-deficient
and wild-type mice that were primed and subsequently infected with heterologous
Borrelia developed severe swelling and histopathological changes of the hind
paws. In addition, Borrelia-primed and -infected IL-17-deficient mice exhibited
elevated gamma-interferon (IFN-gamma) levels in sera and increased frequencies of
IFN-gamma-expressing lymphocytes in popliteal lymph nodes compared to Borrelia
primed and -infected wild-type mice. These results demonstrate that IL-17 is not
required for development of severe pathology in response to infection with
Borrelia burgdorferi, but may contribute to disease through an interaction with
IFN-gamma.
PMID- 27493063
TI - Inflammation-associated cytokine analysis identifies presence of respiratory
bacterial pathogens in the nasopharynx.
AB - We sought to determine if inflammatory cytokines are induced during asymptomatic
nasopharyngeal (NP) colonization by the common respiratory bacteria Streptococcus
pneumoniae (Spn), non-typeable Haemophilus influenzae (NTHi) and Moraxella
catarrhalis (Mcat). 85 serum samples were studied from 85 children 6-36 months of
age when children were healthy and potentially NP colonized with Spn, NTHi or
Mcat. Immunoassays were used to quantitate serum sICAM-1, IL-10 and S100A12
levels. Logistic regression was used to develop a predictive model for NP
colonization probability for causative bacterial pathogen presence. Serum levels
of sICAM-1, IL-10 and S100A12 increased during asymptomatic NP colonization by
Spn, NTHi and Mcat. In a statistical model using risk scoring, we found high
positive predictive and negative value, sensitivity and specificity when using
these three cytokines to identify the presence of Spn, NTHi and Mcat in the NP.
For the first time, we show that inflammatory cytokines are induced in serum
during asymptomatic NP colonization by Spn, NTHi and Mcat.
PMID- 27493065
TI - Fe3O4@mSiO2-FA-CuS-PEG nanocomposites for magnetic resonance imaging and targeted
chemo-photothermal synergistic therapy of cancer cells.
AB - In this work, a new multifunctional nanoplatform (Fe3O4@mSiO2-FA-CuS-PEG
nanocomposite) for magnetic resonance imaging (MRI) and targeted chemo
photothermal therapy, was firstly fabricated on the basis of magnetic mesoporous
silica nanoparticles (Fe3O4@mSiO2), on which folic acid (FA) was grafted as the
targeting reagent, CuS nanocrystals were attached as the photothermal agent, and
polyethylene glycol (PEG) was coupled to improve biocompatibility. The
characterization results demonstrated that the fabricated Fe3O4@mSiO2-FA-CuS-PEG
nanocomposites not only showed strong magnetism and excellent MRI performance,
but also had a high doxorubicin (DOX, an anticancer drug) loading capacity
(22.1%). The loaded DOX can be sustainably released, which was apt to be
controlled by pH adjustment and near infrared (NIR) laser irradiation. More
importantly, targeted delivery of the DOX-loaded Fe3O4@mSiO2-FA-CuS-PEG
nanocomposites could be accomplished in HeLa cells via the receptor-mediated
endocytosis pathway, and this exhibited synergistic effect of chemotherapy and
photothermal therapy against HeLa cells under irradiation with a 915 nm laser.
Therefore, the fabricated multifunctional Fe3O4@mSiO2-FA-CuS-PEG nanocomposite
has a great potential in image-guided therapy of cancers.
PMID- 27493064
TI - Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6.
AB - Cellular informational and metabolic processes are propagated with specific
membrane fusions governed by soluble N-ethylmaleimide sensitive factor attachment
protein receptors (SNARE). SNARE protein Ykt6 is highly expressed in brain
neurons and plays a critical role in the membrane-trafficking process. Studies
suggested that Ykt6 undergoes a conformational change at the interface between
its longin domain and the SNARE core. In this work, we study the conformational
state distributions and dynamics of rat Ykt6 by means of single-molecule Forster
Resonance Energy Transfer (smFRET) and Fluorescence Cross-Correlation
Spectroscopy (FCCS). We observed that intramolecular conformational dynamics
between longin domain and SNARE core occurred at the timescale ~200 MUs.
Furthermore, this dynamics can be regulated and even eliminated by the presence
of lipid dodecylphoshpocholine (DPC). Our molecular dynamic (MD) simulations have
shown that, the SNARE core exhibits a flexible structure while the longin domain
retains relatively stable in apo state. Combining single molecule experiments and
theoretical MD simulations, we are the first to provide a quantitative dynamics
of Ykt6 and explain the functional conformational change from a qualitative point
of view.
PMID- 27493066
TI - Toward Better Pain Management: The Development of a "Pain Stewardship Program" in
a Tertiary Children's Hospital.
AB - OBJECTIVE: Despite increased focus on pediatric pain, uncontrolled pain is still
a problem for hospitalized pediatric inpatients. A program was designed to find
patients with uncontrolled pain and develop a framework to oversee their pain
management. This report details the development of a pain stewardship program
with data from the first year of its activity. METHODS: Hospitalized inpatients
in a tertiary care pediatric center in the mid-Atlantic region were included in
the study. Pain scores are recorded every 4 hours in the hospital electronic
health record. A report was constructed to find all patients with an average pain
score >=7 in the preceding 12 hours. The charts of these patients were reviewed
by our anesthesia pain service, and all patients were grouped into 1 of the
following action categories: (1) no action required; (2) telephone call to the
patient's attending physician; (3) one-time consultation; (4) consultation with
ongoing management; or (5) patient was already on the anesthesia pain service.
Demographic data, pain regimens, and outcomes were recorded in a prospectively
collected database. RESULTS: There were 843 records on 441 unique patients. Only
22% required action to be taken by the anesthesia pain service. The pain
stewardship database revealed that patients with sickle cell disease or abdominal
pain required more frequent attention. CONCLUSIONS: An electronic health record
based pain stewardship program is an important step in identifying all children
in the hospital with undermanaged pain, and it provides a warning system that may
improve patient care, outcomes, and satisfaction.
PMID- 27493067
TI - Acceptability of a Community-Based Outreach HIV-Testing Intervention Using Oral
Fluid Collection Devices and Web-Based HIV Test Result Collection Among Sub
Saharan African Migrants: A Mixed-Method Study.
AB - BACKGROUND: Late human immunodeficiency virus (HIV) diagnosis is common among sub
Saharan African migrants. To address their barriers to HIV testing uptake and
improve timely HIV diagnoses and linkage to care, the outreach HIV testing
intervention, "swab2know," was developed. It combined a community-based approach
with innovative testing methods: oral fluid self-sampling and the choice between
Web-based HIV test result collections using a secured website or post-test
counseling at a sexual health clinic. The sessions included an informational
speech delivered by a physician of sub-Saharan African origin and testimonies by
community members living with HIV. OBJECTIVES: The objectives of this study were
to evaluate the intervention's acceptability among sub-Saharan African migrants
and its potential to reach subgroups at higher risk for HIV infection and to
identify facilitators and barriers for HIV testing uptake. METHODS: This mixed
method study combined qualitative (participant observations and informal
interviews with testers and nontesters) and quantitative data (paper-pencil
survey, laboratory data, and result collection files). Data were analyzed using a
content analytical approach for qualitative and univariate analysis for
quantitative data. RESULTS: A total of 10 testing sessions were organized in sub
Saharan African migrant community venues in the city of Antwerp, Belgium, between
December 2012 and June 2013. Overall, 18.2% of all people present (N=780)
underwent HIV testing; 29.8% of them tested for HIV for the first time, 22.3% did
not have a general practitioner, and 21.5% reported 2 or more sexual partners
(last 3 months). Overall, 56.3% of participants chose to collect their HIV test
results via the protected website. In total, 78.9% collected their results. The
qualitative analysis of 137 participant observation field notes showed that
personal needs and Internet literacy determined the choice of result collection
method. Generally, the oral fluid collection devices were well accepted mainly
because sub-Saharan African migrants dislike blood taking. For some participants,
the method raised concerns about HIV transmission via saliva. The combination of
information sessions, testimonies, and oral fluid collection devices was
perceived as effectively reducing thresholds to participation. Acceptability of
the intervention differed between individual participants and settings.
Acceptance was higher among women, in churches and settings where community
leaders were engaged in HIV awareness raising. Higher preventive outcomes were
observed in settings with lower acceptance. The presence of the intervention team
visualized the magnitude of the HIV epidemic to the public and promoted HIV
testing uptake at large, for example, those who declined indicated they would
take up testing later. CONCLUSIONS: When accompanied by tailored provision of
information, outreach HIV testing interventions adopting a community-based
approach and innovative methods such as Web-based result collection and oral
fluid collection devices are acceptable and reduce thresholds for HIV testing
uptake. The swab2know intervention was able to reach sub-Saharan African migrants
at risk of HIV infection, and with limited access to regular HIV testing. Among
nontesters, the intervention contributed to awareness raising and therefore has a
place in a multipronged HIV test promotion strategy.
PMID- 27493068
TI - Badgers prefer cattle pasture but avoid cattle: implications for bovine
tuberculosis control.
AB - Effective management of infectious disease relies upon understanding mechanisms
of pathogen transmission. In particular, while models of disease dynamics usually
assume transmission through direct contact, transmission through environmental
contamination can cause different dynamics. We used Global Positioning System
(GPS) collars and proximity-sensing contact-collars to explore opportunities for
transmission of Mycobacterium bovis [causal agent of bovine tuberculosis] between
cattle and badgers (Meles meles). Cattle pasture was badgers' most preferred
habitat. Nevertheless, although collared cattle spent 2914 collar-nights in the
home ranges of contact-collared badgers, and 5380 collar-nights in the home
ranges of GPS-collared badgers, we detected no direct contacts between the two
species. Simultaneous GPS-tracking revealed that badgers preferred land > 50 m
from cattle. Very infrequent direct contact indicates that badger-to-cattle and
cattle-to-badger M. bovis transmission may typically occur through contamination
of the two species' shared environment. This information should help to inform
tuberculosis control by guiding both modelling and farm management.
PMID- 27493069
TI - Gold Nanocups: Colloidal Gold Nanocups with Orientation-Dependent Plasmonic
Properties (Adv. Mater. 30/2016).
AB - On page 6322, J. F. Wang and co-workers report a wet-chemistry method for the
preparation of colloidal Au nanocups and their plasmonic properties. The Au
nanocups are prepared through single-vertex-initiated Au deposition on PbS nano
octahedrons and subsequent selective dissolution of PbS. Owing to the orientation
dependent coupling strengths, the obtained Au nanocups display orientation
dependent plasmonic properties and Raman enhancements when deposited on
substrates.
PMID- 27493072
TI - Antimonene: Mechanical Isolation of Highly Stable Antimonene under Ambient
Conditions (Adv. Mater. 30/2016).
AB - On page 6332, J. Gomez-Herrero, F. Zamora, and co-workers describe the isolation
of antimonene, a new allotrope of antimony that consists of a single layer of
atoms. They obtain antimonene flakes by the scotch tape method; these flakes are
highly stable in ambient conditions and even when immersed in water. The 1.2 eV
gap calculated in this study suggests potential applications in optoelectronics.
PMID- 27493071
TI - Zinc-Air Batteries: Flexible Rechargeable Zinc-Air Batteries through
Morphological Emulation of Human Hair Array (Adv. Mater. 30/2016).
AB - On page 6421, Z. Chen and co-workers describe an electrically rechargeable,
nanoarchitectured air electrode that morphologically emulates a human-hair array
for solid-state zinc-air batteries. Grown directly on a stainless-steel mesh, the
hair-like array can effectively catalyze molecular oxygen to water. Batteries
equipped with this electrode show tangible benefits, including improved
flexibility and performance.
PMID- 27493073
TI - Nanoscale Electrodes: Nanoscale Electrodes for Flexible Electronics by Swelling
Controlled Cracking (Adv. Mater. 30/2016).
AB - The fabrication of nanospaced electrodes on a flexible substrate is a great
challenge. W. Wang, J. Shao, and co-workers propose a novel approach to fabricate
nanogap electrodes for flexible electronics using a swelling-controlled cracking
method, which is described on page 6337. This method has the advantages of high
applicability, parallel manufacturing capacity, and compatibility with flexible
substrates. It provides a new way to create high-performance flexible electronics
in a cost-efficient fashion.
PMID- 27493075
TI - Transgenic approach to express the channelrhodopsin 2 gene in arginine
vasopressin neurons of rats.
AB - Optogenetics provides a powerful tool to regulate neuronal activity by light
sensitive ion channels such as channelrhodopsin 2 (ChR2). Arginine vasopressin
(AVP; also known as the anti-diuretic hormone) is a multifunctional hormone which
is synthesized in the magnocellular neurosecretory cells (MNCs) of the
hypothalamus. Here, we have generated a transgenic rat that expresses an AVP-ChR2
enhanced green fluorescent protein (eGFP) fusion gene in the MNCs of the
hypothalamus. The eGFP fluorescence that indicates the expression of ChR2-eGFP
was observed in the supraoptic nucleus (SON) and in the magnocellular division of
the paraventricular nucleus (PVN) that is known to contain AVP-secreting neurons.
The eGFP fluorescence intensities in those nuclei and posterior pituitary were
markedly increased after chronic salt loading (2% NaCl in drinking water for
5days). ChR2-eGFP was localized mainly in the membrane of AVP-positive MNCs.
Whole-cell patch-clamp recordings were performed from single MNCs isolated from
the SON of the transgenic rats, and blue light evoked repetitive action
potentials. Our work provides for the first time an optogenetic approach to
selectively activate AVP neurons in the rat.
PMID- 27493076
TI - Advanced age negatively impacts survival in an experimental brain tumor model.
AB - Glioblastoma (GBM) is the most common primary malignant brain tumor in adults,
with an average age of 64 years at the time of diagnosis. To study GBM, a number
of mouse brain tumor models have been utilized. In these animal models, subjects
tend to range from 6 to 12 weeks of age, which is analogous to that of a human
teenager. Here, we examined the impact of age on host immunity and the gene
expression associated with immune evasion in immunocompetent mice engrafted with
syngeneic intracranial GL261. The data indicate that, in mice with brain tumors,
youth conveys an advantage to survival. While age did not affect the tumor
infiltrating T cell phenotype or quantity, we discovered that old mice express
higher levels of the immunoevasion enzyme, IDO1, which was decreased by the
presence of brain tumor. Interestingly, other genes associated with promoting
immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age.
These data highlight the possibility that IDO1 contributes to faster GBM
outgrowth with advanced age, providing rationale for future investigation into
immunotherapeutic targeting in the future.
PMID- 27493077
TI - Polyphenols in dementia: From molecular basis to clinical trials.
AB - Dementia is common in the elderly, but there are currently no effective therapies
available to prevent or treat this syndrome. In the last decade, polyphenols
(particularly curcumin, resveratrol and tea catechins) have been under very close
scrutiny as potential therapeutic agents for neurodegenerative diseases,
diabetes, inflammatory diseases and aging. Data were collected from Web of
Science (ISI Web of Knowledge), Pubmed and Medline (from 2000 to 2015), by
searching for the keywords "dementia" AND "curcumin", "resveratrol", "EGCG", "tea
catechins". The same keywords were used to investigate the current state of
clinical trials recorded in the NIH clinicaltrials.gov registry. Starting from
the intrinsic properties of the compounds, we explain their specific action in
patients with AD and the most common types of dementia. The pharmacological
actions of curcumin, resveratrol and tea catechins have mainly been attributed to
their antioxidant activity, interaction with cell signaling pathways, anti
inflammatory effect, chelation of metal ions, and neuroprotection. Evidence from
in vitro and in vivo studies on polyphenols have demonstrated that they may play
an integral role in preventing and treating diseases associated with
neurodegeneration. Furthermore, we critically analyze the clinical trials that we
found, which investigate the real pharmacological actions and the possible side
effects of these compounds. This review highlights the potential role of
polyphenols in the prevention/treatment of dementia and describes the current
limitations of research in this field.
PMID- 27493078
TI - A highly reproducible mice model of chronic kidney disease: Evidences of
behavioural abnormalities and blood-brain barrier disruption.
AB - AIMS: In the present study, a novel mice model of chronic kidney disease (CKD)
was developed, and psycho-motor behavioural abnormalities, blood-brain barrier
(BBB) integrity and brain histology were studied. MAIN METHODS: Swiss albino
female mice were given high adenine diet (0.3% w/w mixed with feed) for 4weeks.
Serum urea and creatinine levels and renal histological studies were performed to
validate the model. Psycho-motor behavioural abnormalities and neurological
severity were studied. BBB integrity was assessed using Evans blue extravasation
method. Nissl staining was performed to see possible morphological aberrations in
brain. KEY FINDINGS: There was a significant increase in serum urea and
creatinine levels in mice given high adenine diet, and the mice had abnormal
kidney morphology. Deposition of adenine and 2,8-dihydroxyadenine crystals, and
increased collagen deposits in the renal tissues were found, which validate
induction of CKD in the mice. Motor behavioural abnormalities, depression-like
and anxiolytic behaviour and increase in neurological severity were prevalent in
mice with CKD. Evans Blue dye extravasation was found to occur in the brain,
which signifies disruption of BBB. However, Nissl staining did not reveal any
morphological aberration in brain tissue. SIGNIFICANCE: The present study puts
forward a highly reproducible mice model of CKD validated with serum parameters
and renal histopathological changes. The mice showed psycho-motor behavioural
abnormalities and BBB disruption. It is a convenient model to study the disease
pathology, and understanding the associated disorders, and their therapeutic
interventions.
PMID- 27493079
TI - Diabetes and exposure to peritoneal dialysis solutions alter tight junction
proteins and glucose transporters of rat peritoneal mesothelial cells.
AB - AIM: To evaluate alterations in tight junction (TJ) proteins and glucose
transporters in rat peritoneal mesothelial cells (RPMC) from diabetic rats and
after treatment with peritoneal dialysis solutions (PDS) in vitro. METHODS:
Diabetes was induced in female Wistar rats by streptozotocin (STZ)-injection.
Twenty-one days after STZ-injection, peritoneal thickness and mesothelial cell
morphology were studied by light microscopy and microvilli length and density by
atomic force microscopy. RPMC were obtained from healthy and diabetic rats.
Mesothelial phenotype, evaluated by cytokeratin and pan-cadherin, epithelial to
mesenchymal transition (EMT), evaluated by alpha-smooth muscle action (alpha-SMA)
and vimentin, TJ proteins, claudins-1 and -2, and occludin, and glucose
transporters, sodium and glucose co-transporters (SGLT) -1 and -2 and
facilitative glucose transporters (GLUT) -1 and -2 were analyzed. Also,
transepithelial electrical resistance (TER) was measured. Oxidative stress was
estimated by measuring reactive oxygen species production, and protein
carbonylation, receptor for advanced glycation end products (RAGE), nuclear
factor erythroid related factor-2 (Nrf-2), and expression of antioxidant enzymes.
KEY FINDINGS: Peritoneal damage was present 21days after STZ-injection. Diabetes
induced changes in TJ and glucose transporters in RPMC together with decreased
TER. RPMC from diabetic rats showed oxidative stress, which was enhanced by
exposure to PDS. In addition, RPMC from diabetic rats showed early EMT.
SIGNIFICANCE: To our knowledge, this is the first study that shows changes in TJ
proteins and glucose transporters of RPMC from diabetic rats. All these
alterations might explain the increased peritoneal permeability observed in
diabetic patients undergoing peritoneal dialysis.
PMID- 27493080
TI - Cytomorphology and Clinicopathologic Correlation of the Recurrent and Metastatic
Adult Granulosa Cell Tumor of the Ovary: A Retrospective Review.
AB - Granulosa cell tumors (GCT) of the ovary are low grade tumor with a potential
ability of late pelvic recurrences and distant metastases. However, there is
sparse literature on the cytopathologic features of metastatic granulosa cell
tumors (MGCT). Between 2000 and 2014, eight cases of MGCT were diagnosed by FNA.
Clinical, cytologic, and histopathologic features were reviewed. The age ranged
from 34 to 84 years. Metastases were found in abdominal wall (4 cases), pelvic
mass (1 case), liver (2 cases), and lung (1 case). The time to metastasis ranged
from 1 to 14 years. All cases were hypercellular, with both large and small
overlapping cell clusters and individual cells. The cytologic features included:
naked nuclei (8/8 cases), Call-Exner bodies (2/8 cases), and prominent
metachromatic stroma (3/8 cases). Moderate cytoplasm (4/8 cases) to scant
delicate cytoplasm (4/8 cases) was seen. Cytoplasmic vacuoles were also noted
(6/8 cases). N/C ratios were high although lower than small round cell tumors
like lymphoma. Prominent, central nucleoli were also present (6/8 cases) as well
as nuclear grooves (2/8 cases). Cell block was available in 3/8 cases and all
were positive for inhibin immunostain. Histologic examination of the metastatic
tissue confirmed MGCT. The important cytologic features of GCT like uniformity of
tumor cells, nuclear grooves and Call-Exner bodies are occasionally present in
MGCT. Prominent nucleoli and many naked nuclei were frequent. Therefore, the
accurate interpretation of cytologic findings of MGCT requires cytohistologic
correlation and inhibin positivity to avoid unnecessary surgical interventions
for diagnostic purposes. The possibility of late recurrence of GCT should be kept
in mind. Diagn. Cytopathol. 2016;44:1058-1063. (c) 2016 Wiley Periodicals, Inc.
PMID- 27493081
TI - Host Th1/Th2 immune response to Taenia solium cyst antigens in relation to cyst
burden of neurocysticercosis.
AB - Neurocysticercosis (NCC), Taenia solium larval infection of the brain, is an
important cause of acquired seizures in endemic countries, which relate to
number, location and degenerating cysts in the brain. Multicyst infections are
common in endemic countries although single-cyst infection prevails in India.
Single-cyst infections in an endemic country suggest a role for host immunity
limiting the infection. This study examined ex vivo CD4(+) T cells and in vitro
Th1 and Th2 cytokine responses to T. solium cyst antigens of peripheral blood
mononuclear cells of healthy subjects from endemic and nonendemic regions and of
single- and multicyst-infected patients for association with cyst burden of NCC.
T. solium cyst antigens elicited a Th1 cytokine response in healthy subjects of
T. solium-endemic and T. solium-non-endemic regions and those with single-cyst
infections and a Th2 cytokine response from subjects with multicyst
neurocysticercosis. Multicyst neurocysticercosis subjects also exhibited low
levels of effector memory CD4(+) T cells. Th1 cytokine response of T. solium
exposure and low infectious loads may aid in limiting cyst number. Th2 cytokines
and low effector T cells may enable multiple-cyst infections to establish and
persist.
PMID- 27493083
TI - Infective endocarditis in patients with bicuspid aortic valve: Clinical
characteristics, complications, and prognosis.
AB - INTRODUCTION: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac
disease. It is associated to a higher risk of cardiovascular complications,
including infective endocarditis (IE). METHODS: Retrospective, observational and
single centre study that included all patients with IE diagnosed between 1996 and
2014. An analysis was made of the epidemiological, clinical, microbiological and
echocardiographic data, complications during hospital admission, need for
surgery, in-hospital mortality, and 1-year follow-up. Cases with endocarditis on
prosthetic valves or other locations were excluded, as well as those for which
the aortic valve morphology had not been accurately defined. A comparative
statistical analysis was performed between BAV and tricuspid (TAV). RESULTS: Of a
total of 328 cases with IE, 118 (35.67%) were on aortic valve, with 18 (16.22%)
of them being BAV. The BAV cases were younger than TAV (51+/-19.06 vs. 60.83+/
15.73 years, P=.021) and they had less comorbidity (Charlson 0.67+/-0.77 vs.
1.44+/-1.64, P=.03).). There was a higher tendency of Staphylococcal origin (38.9
vs. 21.5%, P=.137), and 55.6% showed peri-valvular complications (TAV 16.1%,
P=.001), in particular, abscesses (38.9 vs.16.1%, P=.047). BAV was the only
predictive factor of peri-valvular complications (OR 7.87, 95% CI; 2.38-26.64,
P=.001). Patients with BAV had more surgery during their admission (83.3 vs.
44.1%, P=.004), had less in-hospital mortality, with no statistical significance
(5.6 vs. 25.8%, P=.069), and 1-year survival was significantly superior (93.8 vs
69.3%, P=.048). CONCLUSIONS: Patients with IE on BAV are young, with low
comorbidity. They frequently present with peri-valvular complications and they
often require early surgery. Compared to TAV cases, in-hospital mortality is
lower and 1-year survival is significantly higher.
PMID- 27493082
TI - Fibrous dysplasia of bone: craniofacial and dental implications.
AB - Fibrous dysplasia (FD) is a rare bone disease caused by postzygotic somatic
activating mutations in the GNAS gene, which lead to constitutive activation of
adenylyl cyclase and elevated levels of cyclic AMP, which act on downstream
signaling pathways and cause normal bone to be replaced with fibrous tissue and
abnormal (woven) bone. The bone disease may occur in one bone (monostotic),
multiple bones (polyostotic), or in combination with hyperfunctioning
endocrinopathies and hyperpigmented skin lesions (in the setting of McCune
Albright Syndrome). FD is common in the craniofacial skeleton, causing
significant dysmorphic features, bone pain, and dental anomalies. This review
summarizes the pathophysiology, clinical findings, and treatment of FD, with an
emphasis on the craniofacial and oral manifestations of the disease.
PMID- 27493084
TI - Life Lessons for Successful Leadership.
PMID- 27493085
TI - How Hard Could It Be?
PMID- 27493086
TI - The Fellowship Arms Race Revisited.
PMID- 27493087
TI - Avoid "Short-Term": Use Units of Time for Follow-Up Recommendations.
PMID- 27493088
TI - H/KDEL receptors mediate host cell intoxication by a viral A/B toxin in yeast.
AB - A/B toxins such as cholera toxin, Pseudomonas exotoxin and killer toxin K28
contain a KDEL-like amino acid motif at one of their subunits which ensures
retrograde toxin transport through the secretory pathway of a target cell. As key
step in host cell invasion, each toxin binds to distinct plasma membrane
receptors that are utilized for cell entry. Despite intensive efforts, some of
these receptors are still unknown. Here we identify the yeast H/KDEL receptor
Erd2p as membrane receptor of K28, a viral A/B toxin carrying an HDEL motif at
its cell binding beta-subunit. While initial toxin binding to the yeast cell wall
is unaffected in cells lacking Erd2p, binding to spheroplasts and in vivo
toxicity strongly depend on the presence of Erd2p. Consistently, Erd2p is not
restricted to membranes of the early secretory pathway but extends to the plasma
membrane where it binds and internalizes HDEL-cargo such as K28 toxin, GFP(HDEL)
and Kar2p. Since human KDEL receptors are fully functional in yeast and restore
toxin sensitivity in the absence of endogenous Erd2p, toxin uptake by H/KDEL
receptors at the cell surface might likewise contribute to the intoxication
efficiency of A/B toxins carrying a KDEL-motif at their cytotoxic A-subunit(s).
PMID- 27493089
TI - Anti-apoptotic effect of interleukin-22 on fibroblast-like synoviocytes in
patients with rheumatoid arthritis is mediated via the signal transducer and
activator of transcription 3 signaling pathway.
AB - AIM: Inadequate apoptosis of fibroblast-like synoviocytes (FLS) plays a crucial
role in the immunopathogenesis of rheumatoid arthritis (RA). Interleukin-22 (IL
22) is a novel member of the cytokine network that has been found to be involved
in the immunological process underlying RA. In this study, we investigated the
effect of IL-22 on the survival of RA-FLS from RA patients and examined the
possible mechanism to determine new therapeutic strategies for RA. METHODS: FLS
obtained from patients with RA were cultured in vitro and treated with sodium
nitroprussiate (SNP) to induce apoptosis in the presence or absence of IL-22. RA
FLS viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. RA-FLS apoptosis was analyzed by annexin
V/propidium iodide staining (AV/PI). The levels of IL-22R1, pSTAT3-Y705, pSTAT3
S727, total STAT3, Bcl-xL and Bcl-2 were detected by Western blot analysis.
RESULTS: IL-22R1 was expressed on RA-FLS. IL-22 pretreatment at concentrations
ranging from 10 to 100 ng/mL increased RA-FLS viability and prevented SNP-induced
apoptosis. Treatment with the STAT3 inhibitors, HO3867 or STA21, reversed the
protective effect of IL-22 on SNP-induced apoptosis of RA-FLS. IL-22-induced
phosphorylation of STAT3 (pSTAT3-Y705 and pSTAT3-S727) was increased in RA-FLS.
Also IL-22 increased Bcl-2 expression in SNP-treated RA-FLS, and the effect was
reversed by treatment with HO3867 or STA21. CONCLUSION: IL-22 protects against
SNP-induced apoptosis in RA-FLS by activating the STAT3 pathway and the
downstream target gene, Bcl-2. Therefore, therapeutic strategies that target the
IL-22/STAT3 pathway are implicated as candidates for RA treatment.
PMID- 27493090
TI - Early progression of proximal intramural hematoma to overt aortic dissection
during initial computed tomographic evaluation.
PMID- 27493091
TI - CASE 9-2016: Management of a Former Cardiac Anesthesiologist With Increasing
Aortic Stenosis Requiring Aortic Valve Replacement.
PMID- 27493092
TI - Efficacy and Safety of Fibrinogen Concentrate in Surgical Patients: A Meta
Analysis of Randomized Controlled Trials.
AB - OBJECTIVES: To investigate the efficacy and safety of fibrinogen concentrate (FC)
in surgical patients. DESIGN: Meta-analysis of randomized controlled studies
(RCTs). SETTING: Perioperative. PARTICIPANTS: Adult and pediatric surgical
patients. INTERVENTIONS: A search of PubMed/Medline, Embase, Cochrane Central
Register of Controlled Trials, Transfusion Evidence Library, Google Scholar, and
the proceedings from major international anesthesiology meetings up to February
1, 2016 for RCTs that compared FC with placebo or other comparators. MEASUREMENTS
AND MAIN RESULTS: The primary outcome was all-cause mortality. Pooled risk ratios
and mean differences (MDs) were computed with either fixed-effects or random
effects models. The study included 14 RCTs comprising 1,035 patients; the
majority of patients underwent cardiac surgery. All-cause mortality was lower in
the fibrinogen group (4/432 [0.9%] v 15/430 [3.5%]; risk ratio 0.26; 95%
confidence interval [CI] 0.09-0.78; p = 0.02; heterogeneity statistic (l2) = 0%).
The use of FC was associated with reduced bleeding (MD -127 mL; 95% CI -207 to
47; p = 0.002; I2= 54%) and a lower number of red blood cells units transfused
versus comparator (MD -0.9; 95% CI -1.3 to -0.5; p<0.001; I2 = 42%). There were
no differences in the rates of thrombotic events and myocardial infarction.
CONCLUSIONS: In surgical patients, FC was associated with reduced bleeding and a
lower number of red blood cell units transfused, and it also might reduce
mortality. However, none of the analyzed trials was powered for estimation of
survival and adverse events with FC use. Half of the included studies were of
high or moderate risk of bias. The evidence primarily came from cardiac surgery
settings.
PMID- 27493093
TI - A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass.
AB - OBJECTIVE: This study investigated postoperative hemostasis of patients subjected
to conventional protamine dosing compared with protamine dosing based on a
pharmacokinetic (PK) model following cardiopulmonary bypass. DESIGN:
Retrospective case-control study. SETTING: Tertiary university hospital.
PARTICIPANTS: Patients undergoing elective cardiac surgery with cardiopulmonary
bypass. INTERVENTIONS: In 56 patients, protamine was dosed in a fixed ratio (CD),
while 62 patients received protamine based on the PK model. MEASUREMENTS AND MAIN
RESULTS: There was no difference in heparin administration (414+/-107 mg (CD) v
403+/-90 mg (PK); p = 0.54), whereas protamine dosing was considerably different
with a protamine-to-heparin dosing ratio of 1.1+/-0.3 for the CD group and 0.5+/
0.1 for the PK group (p<0.001). The changes in activated coagulation time
(DeltaACT) values (ACT after protamine minus preoperative ACT;+17+/-77 s v+6+/-15
s; p = 0.31) were equal between groups. Yet, the thromboelastometric
intrinsically activated coagulation test clotting time (CT; 250+/-76 s v 203+/-44
s; p<0.001) and intrinsically activated coagulation test without the heparin
effect CT (275+/-105 v 198+/-32 s; p<0.001) were prolonged in the CD group.
Median packed red blood cell transfusion (0 [0-2] v 0 [0-0]), fresh frozen plasma
transfusion (1 [0-2] v 0 [0-0]), and platelet concentrate transfusion (0 [0-1] v
0 [0-0]) were different between the fixed ratio and PK group, respectively (all
p<0.001). CONCLUSIONS: This study showed that patient-tailored protamine dosing
based on a PK model was associated with a reduction in protamine dosing, with
better hemostatic test results when compared with fixed-ratio protamine dosing.
PMID- 27493094
TI - Hyperlactemia Predicts Surgical Mortality in Patients Presenting With Acute
Stanford Type-A Aortic Dissection.
AB - OBJECTIVE: Inspired by the limited facility of the Penn classification, the
authors aimed to determine a rapid and optimal preoperative assessment tool to
predict surgical mortality after acute Stanford type-A aortic dissection (AAAD)
repair. DESIGN: Patients who underwent an attempted surgical repair of AAAD were
determined using a de-identified single institution database. The charts of 144
patients were reviewed retrospectively for preoperative demographics and
surrogates for disease severity and malperfusion. Bivariate analysis was used to
determine significant (p<=0.05) predictors of in-hospital and 1-year mortality,
the primary endpoints. Receiver operating characteristic curve generation was
used to define optimal cut-off values for continuous predictors. SETTING: Single
center, level 1 trauma, university teaching hospital. PARTICIPANTS: The study
included 144 cardiac surgical patients with acute type-A aortic dissection
presenting for surgical correction. INTERVENTIONS: Surgical repair of aortic
dissection with preoperative laboratory samples drawn before patient transfer to
the operating room or immediately after arterial catheter placement
intraoperatively. MEASUREMENTS AND MAIN RESULTS: The study cohort comprised 144
patients. In-hospital mortality was 9%, and the 1-year mortality rate was 17%.
Variables that demonstrated a correlation with in-hospital mortality included an
elevated serum lactic acid level (odds ratio [OR] 1.5 [1.3-1.9], p<0.001), a
depressed ejection fraction (OR 0.91 [0.86-0.96], p = .001), effusion (OR 4.8
[1.02-22.5], p = 0.04), neurologic change (OR 5.3 [1.6-17.4], p = 0.006), severe
aortic regurgitation (OR 8.2 [2.0-33.9], p = 0.006), and cardiopulmonary
resuscitation (OR 6.8 [1.7-26.9], p = 0.01). Only an increased serum lactic acid
level demonstrated a trend with 1-year mortality using univariate Cox regression
(hazard ratio 1.1 [1.0-1.1], p = 0.006). Receiver operating characteristic
analysis revealed optimal cut-off lactic acid levels of 6.0 mmol/L and 6.9 mmol/L
for in-hospital and 1-year mortality, respectively. CONCLUSION: Lactic acidosis,
ostensibly as a surrogate for systemic malperfusion, represents a novel,
accurate, and easily obtainable preoperative predictor of short-term mortality
after attempted AAAD repair. These data may improve identification of patients
who would not benefit from surgery.
PMID- 27493095
TI - MicroRNA-3178 ameliorates inflammation and gastric carcinogenesis promoted by
Helicobacter pylori new toxin, Tip-alpha, by targeting TRAF3.
AB - BACKGROUND: Helicobacter pylori infection is the main cause of chronic gastritis,
peptic ulcer, and gastric cancer. Tip-alpha is a newly identified carcinogenic
factor present in H. pylori. TRAF3 can activate NF-kappaB by both canonical and
noncanonical signaling pathways. In this study, we found that the expression of
TRAF3 and NF-kappaB was upregulated, while microRNA-3178 (miR-3178) was decreased
in H. pylori-positive gastric tissues but not in H. pylori-negative tissues.
MATERIALS AND METHODS: GES-1 cells were incubated with 12.5 MUg/mL recombinant
Tip-alpha (rTip-alpha) in RPMI1640 for 2 hours. After another 24 hours, the
supernatant medium was designed as inflammatory-conditioned medium (ICM) and that
from the untreated control cells was designed as untreated control medium. The
release of proinflammatory cytokines from GES-1 cells and proliferation of
gastric cancer cells was determined by ELISA and CCK-8 kits. Cells were
transfected with the mimic, inhibitor, negative control of miR-3178, or TRAF3
siRNA control siRNA. The medium was then replaced with RPMI1640, 12.5 MUg/mL rTip
alpha, and collected, and the total cellular RNA and protein were extracted for
the following detection. RESULTS: MiR-3178 mimic prevented the increasement of
TRAF3 and hence decreased activation of NF-kappaB signals, whereas miR-3178
inhibitor could not, in GES-1 cells with Tip-alpha treatment. The condition
medium from miR-3178 mimic transfected GES-1 cells could inhibit proliferation
and induce apoptosis of inflammation-related gastric cancer cells SGC7901 and
MGC803 by decreasing the production of inflammatory cytokines TNF-alpha and IL-6,
which were secreted by GES-1 cells. CONCLUSIONS: Taken all together, Tip-alpha
might activate NF-kappaB to promote inflammation and carcinogenesis by inhibiting
miR-3178 expression, which directly targeting TRAF3, during H. pylori infection
in gastric mucosal epithelial cells.
PMID- 27493097
TI - Analysis of allergic immune responses in humanized mice.
AB - Nowadays, more than 25% of the population in industrial countries are affected by
IgE-mediated (atopic) allergic diseases such as allergic rhinitis, asthma and
atopic eczema. Due to intensive research on basis of in vitro studies with human
immune cells and different murine in vivo models of allergy fundamental
mechanisms of allergic immune responses have been elucidated during the last
years. However, human studies are restricted and the immune system of mice
differs from the human immune system in several aspects so that the
transferability of experimental results from mice to men is limited. Humanized
mice represent a new tool to analyze the interaction of human immune cells under
physiological conditions as far as possible, particularly to test novel
therapeutic strategies. This review summarizes the impact of humanized mouse
models for the investigation and treatment of allergic diseases.
PMID- 27493096
TI - Memory T cells in cutaneous leishmaniasis.
AB - Leishmania causes a spectrum of diseases that range from self-healing to fatal
infections. Control of leishmania is dependent upon generating CD4+ Th1 cells
that produce IFNgamma, leading to macrophage activation and killing of the
intracellular parasites. Following resolution of the disease, short-lived
effector T cells, as well as long-lived central memory T cells and skin resident
memory T cells, are retained and able to mediate immunity to a secondary
infection. However, there is no vaccine for leishmaniasis, and the drugs used to
treat the disease can be toxic and ineffective. While a live infection generates
immunity, a successful vaccine will depend upon generating memory T cells that
can be maintained without the continued presence of parasites. Since both central
memory and skin resident memory T cells are long-lived, they may be the
appropriate targets for a leishmaniasis vaccine.
PMID- 27493098
TI - Nerve growth factor facilitates perivascular innervation in neovasculatures of
mice.
AB - It is well known that blood vessels including arterioles have a perivascular
innervation. It is also widely accepted that perivascular nerves maintain
vascular tone and regulate blood flow. Although there are currently prevailing
opinions, unified views on the innervation of microcirculation in any organs have
not been established. The present study was designed to investigate whether there
are perivascular nerves innervated in microvessels and neovessels. Furthermore,
we examined whether nerve growth factor (NGF) can exert a promotional effect on
perivascular nerve innervation in neovessels of Matrigel plugs. A Matrigel was
subcutaneously implanted in mouse. The presence of perivascular nerves in
Matrigel on Day 7-21 after the implantation was immunohistochemically studied.
NGF or saline was subcutaneously administered by an osmotic mini-pump for a
period of 3-14 days. The immunostaining of neovasculatures in Matrigel showed the
presence of perivascular nerves on Day 21 after Matrigel injection. Perivascular
nerve innervation of neovessels within Matrigel implanted in NGF-treated mice was
observed in Day 17 after Matrigel implantation. However, NGF treatment did not
increase numbers of neovessels in Matrigel. These results suggest that
perivascular nerves innervate neovessels as neovasculatures mature and that NGF
accelerates the innervation of perivascular nerves in neovessels.
PMID- 27493099
TI - Deletion of LR11 Attenuates Hypoxia-Induced Pulmonary Arterial Smooth Muscle Cell
Proliferation With Medial Thickening in Mice.
AB - OBJECTIVE: We aimed to determine whether LR11 (low-density lipoprotein receptor
with 11 binding repeats) is a potential key regulator of smooth muscle cell (SMC)
proliferation during the progression of hypoxia-induced medial thickening in mice
and whether sLR11 (soluble LR11) can serve as a biomarker in patients with
pulmonary arterial hypertension. APPROACH AND RESULTS: The role of LR11 in
pulmonary arterial hypertension was investigated using mouse and cell models of
induced hypoxia. The expression of LR11 and of hypoxia-inducible factor-1alpha
was significantly increased in lung tissues from C57Bl/6 mice after 3 weeks of
exposure to hypoxia compared with normoxia. Serum sLR11 levels were also
increased. Physiological and histochemical analyses showed that increased right
ventricular systolic pressure, right ventricular hypertrophy, and medial
thickening induced under hypoxia in wild-type mice were attenuated in LR11(-/-)
mice. The proliferation rates stimulated by hypoxia or platelet-derived growth
factor-BB were attenuated in SMC derived from LR11(-/-) mice, compared with those
from wild-type mice. Exogenous sLR11 protein increased the proliferation rates of
SMC from wild-type mice. The expression of LR11 and hypoxia-inducible factor
1alpha was increased in cultured SMC under hypoxic conditions, and hypoxia
inducible factor-1alpha knockdown almost abolished the induction of LR11. Serum
sLR11 levels were significantly higher in patients with, rather than without,
pulmonary arterial hypertension. sLR11 levels positively correlated with
pulmonary vascular resistance and mean pulmonary arterial pressure. CONCLUSIONS:
LR11 regulated SMC proliferation during the progression of hypoxia-induced medial
thickening in mice. The findings obtained from mice, together with those in
humans, indicate that sLR11 could serve as a novel biomarker that reflects the
pathophysiology of proliferating medial SMC in pulmonary arterial hypertension.
PMID- 27493101
TI - The synergistic effect between vanillin and doxorubicin in ehrlich ascites
carcinoma solid tumor and MCF-7 human breast cancer cell line.
AB - Despite the remarkable anti-tumor activity of doxorubicin (DOX), its clinical
application is limited due to multiple organ toxicities. Products with less side
effects are therefore highly requested. The current study investigated the anti
cancer activities of vanillin against breast cancer and possible synergistic
potentiation of DOX chemotherapeutic effects by vanillin. Vanillin (100mg/kg),
DOX (2mg/kg) and their combination were administered i.p. to solid Ehrlich tumor
bearing mice for 21days. MCF-7 human breast cancer cell line was treated with
vanillin (1 and 2mM), DOX (100MUM) or their combination. Protection against DOX
induced nephrotoxicity was studied in rats that received vanillin (100mg/kg, ip)
for 10days with a single dose of DOX (15mg/kg) on day 6. Vanillin exerted
anticancer effects comparable to DOX and synergesticlly potentiated DOX
anticancer effects both in-vivo and in-vitro. The anticancer potency of vanillin
in-vivo was mediated via apoptosis and antioxidant capacity. It also offered an
in-vitro growth inhibitory effect and cytotoxicity mediated by apoptosis
(increased caspase-9 and Bax:Bcl-2 ratio) along with anti-metasasis effect.
Vanillin protected against DOX-induced nephrotoxicity in rats. In conclusion,
vanillin can be a potential lead molecule for the development of non-toxic agents
for the treatment of breast cancer either alone or combined with DOX.
PMID- 27493100
TI - Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin
System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.
AB - OBJECTIVE: To determine the effect of probucol on urine albumin excretion in type
2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme
inhibitors or angiotensin receptor blockers. APPROACH AND RESULTS: This was a 16
week, phase II, randomized, placebo-controlled, parallel-group study in type 2
diabetes mellitus patients with a urinary albumin/creatinine ratio of >=300 mg/g
using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,
conducted in 17 tertiary referral hospitals. Eligible patients were randomized to
probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in
a ratio of 1:1:1 after block randomization procedures, keeping the treatment
assignment blinded to the investigators, patients, and study assistants. The
primary end point was change in the geometric mean of urinary albumin/creatinine
ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The
study was started on November 8, 2012, and completed on March 24, 2014. The least
squares mean change+/-SE from baseline in urinary albumin/creatinine ratio at
week 16 was -7.2+/-639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077
versus placebo group), 9.3+/-587.4 mg/g in the probucol 500 mg/d group (n=40;
P=0.1975 versus placebo group), and 259.0+/-969.1 mg/g in the placebo group
(n=41). Although the majority of subjects were on statins, probucol treatment
significantly lowered total cholesterol and low-density lipoprotein cholesterol
levels. QT prolongation occurred in one and two subjects in control and probucol
250 mg/d groups, respectively. CONCLUSIONS: Four months of probucol up to 500
mg/d failed to reduce urinary albumin excretion.
PMID- 27493102
TI - Involvement of mast cells and microvessels density in reactive lesions of oral
cavity: A comparative immunohistochemical study.
AB - In view of the similarity of clinicopathological features between reactive
lesions of the oral cavity, the objective of the present study was to investigate
the density of MCs (mast cells) and microvessels in a series of these lesions.
Thirty-seven cases of reactive lesions including fibrous hyperplasia (FH, n=10),
inflammatory fibrous hyperplasia (IFH, n=10), peripheral giant cell lesion (PGCL,
n=10) and lobular capillary hemangioma (LCH, n=7) were investigated using
immunohistochemistry for mast cell tryptase and CD34. For comparative purposes,
central giant cell lesions (CGCL, n=5) were included. A higher MC density was
observed in LCH (37.01), while CGCL exhibited the lowest density (n=8.14). There
was a significant difference in MC density when all reactive lesions were
compared to CGCL (p=0.001). The largest mean density of microvessels was observed
in LCH (n=21.69). The smallest number was observed in CGCL (n=6.24). There was a
significant difference in microvessel density when the reactive lesions were
compared to CGCL (p=0.003). There was a significant and direct correlation
between the density of MCs and microvessels only for IFH (p=0.048) and CGCL
(p=0.005). A significant and direct correlation between the mean density of MCs
and microvessels was observed when the reactive lesions were analyzed as a whole
(p=0.005). Our results suggest that mast cells contribute to the connective
tissue framework and angiogenic function, as well as the development, of reactive
lesions of the oral cavity, including FH, IFH, LCH and PGCL.
PMID- 27493103
TI - Diastolic dysfunction is associated with low urinary sodium excretion in patients
with decompensated cirrhosis.
AB - BACKGROUND/AIM: The pathogenesis and the clinical impact of diastolic dysfunction
(DD) in cirrhosis remain unclear. Our aim was to investigate the factors
significantly associated with the presence of DD in patients with decompensated
cirrhosis on the waiting list for liver transplantation. MATERIAL AND METHODS:
consecutive patients with decompensated cirrhosis, who admitted for transplant
assessment, were prospectively evaluated. We assessed the independent factors
associated with the presence of DD, while their discriminative ability was
evaluated by AUC curve. The diagnosis of DD was based on Doppler echocardiography
and classified into three categories according to the current guidelines.
RESULTS: we evaluated 115 consecutive patients. Sixty six patients (57.3%-group
1) had DD and 49 (42.7%-group 2) had not DD. The 2 groups had similar Child
Pugh/MELD scores and survival. In multivariable logistic regression analysis,
pulse rate (OR: 1.082, 95% CI: 1.03-1.15, p = 0.004), and UNa24h (OR: 0.98, 95%
CI: 0.97- 0.99, p = 0.004) were the only variables independently associated with
the presence of DD. In the subgroup of consecutive patients (n = 31) with
evaluation of cytokines, those (n = 22) with DD, compared to those (n = 9)
without DD, had significantly higher levels of inteleukin-6 [145 (45-2000) vs. 56
(10-149)pg/mL, p = 0.043]. CONCLUSIONS: We found that DD was independently
associated with lower 24-hour urine sodium. Although no correlation was found
between DD and severity of liver disease or survival, further studies are needed
for final conclusions.
PMID- 27493104
TI - Economic growth leads to increase of obesity and associated hepatocellular
carcinoma in developing countries.
AB - Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer
and the third leading cause of cancer related death worldwide. In recent years,
the prevalence of HCC has increased in both developing and developed countries.
Most HCC cases develop in the presence of advanced chronic liver disease related
to viral hepatitis. In particular hepatitis B virus and hepatitis C virus
infections are considered as major HCC risk factors worldwide. However, current
studies provide strong evidence for increasing numbers of HCC in nonalcoholic
fatty liver disease (NAFLD). NAFLD represents the hepatic manifestation of
metabolic syndrome which is based on obesity and insulin resistance.
Epidemiologic data clearly demonstrates that NAFLD and obesity-related disorders
are significant risk factors for tumor development in general and HCC in
particular. As a consequence of life style changes towards higher calorie intake
and less exercise, obesity and metabolic syndrome are spreading all over the
world. Due to this increase in obesity and metabolic syndrome NAFLD-related HCC
will become a major health care problem in the future. In conclusion, better
understanding of the impact of NAFLD and obesity in the development of HCC will
improve our treatment strategies of HCC and allow preventive measures.
PMID- 27493105
TI - NASH: A glance at the landscape of pharmacological treatment.
AB - The role of nonalcoholic fatty liver disease, namely nonalcoholic
steatohepatitis (NASH), as risk factor for liver- and non-liver-related morbidity
and mortality has been extensively reported. In addition to lifestyle changes,
capable of removing the metabolic factors driving disease progression, there is
an urgent need for drugs able to reduce hepatic necroinflammation without
worsening of fibrosis. This goal is considered by regulatory agencies as
surrogate marker to define the effectiveness in pharmacological compounds in
NASH, and fast-track approval was granted by the Food and Drug Administration in
consideration of disease severity and unmet medical needs. Several compounds are
in the pipeline of pharmaceutical industries and are being studied in phase II
trials, but only a few (obeticholic acid, elafibranor) have started phase III
trials. This concise review is intended to offer a systematic analysis of the
most promising therapeutic intervention in NASH. In conclusion, there is
reasonable expectation that drug may help curb the burden of NASH, and we look
forward to obtaining solid data on their long-term safety and effectiveness.
However, we should not forget that behavioral interventions remain a mandatory
background treatment, able to stop disease progression in compliant overweight/
obese patients, with results that compare favorably with - and add to - the
beneficial effects of drug treatment.
PMID- 27493106
TI - Assessment of intrahepatic regulatory T cells in children with autoimmune
hepatitis.
AB - Background. T-cell populations regulate the balance of immune responses. The CD
(Cluster of differentiation) 4+CD25+ regulatory T cells (Tregs) are crucial for
maintaining negative control of various immune responses. There are different T
cell subpopulations with regulatory functions, as natural killer T cells, CD8+
and CD28. The forkhead box P3 (FOXP3) regulates Treg development and is required
for its suppressive function. AIM: To evaluate the hepatic expression of the
intrahepatic Tregs, Ig (immunoglobulin) G and IgM plasma cells in autoimmune
hepatitis (AIH) and other chronic liver diseases (CLDs). MATERIAL AND METHODS:
This study included 100 pediatric patients; 50 AIH and 50 CLDs other than AIH.
All patients were subjected to routine investigations of CLDs plus immune
staining of liver tissue for FOXp3, IgG and IgM plasma cells, CD4 and CD8 T
cells. RESULTS: The FOXP3+ T cells in patients with AIH (6.3 +/- 5) were
significantly higher than that in the non-AIH (2.1 +/- 2.6). FOXP3+ T cells were
abundant in liver tissue with marked inflammatory cellular infiltrate. CD4+ and
CD8+ infiltrating the liver tissue and IgG positive cells were significantly
higher in AIH group, while the expression of IgM positive cells showed no
significant difference. The IgG/IgM was significantly higher in the AIH treatment
responders (3 +/- 3) than non-responders (1.6 +/- 0.5), while there was no
significant difference regarding the intrahepatic expression of FOXP3+, CD4+,
CD8+ cells, T-cells, IgG and IgM plasma cells. CONCLUSION: Intrahepatic Tregs
were increased in number in patients with AIH in the initial presentation, and
their presence is associated with increased activity and inflammation in liver
biopsy.
PMID- 27493107
TI - HAV and HBV seroprevalence in 1,000 patients with chronic HCV infection in a
Tertiary Care Center in Sao Paulo, Brazil.
AB - Background. Patients with chronic HCV infection and superinfection by hepatitis
A virus (HAV) or hepatitis B virus (HBV) have higher morbidity and mortality when
compared with those without HCV infection. Therefore, HAV and HBV active
immunization has become mandatory in this population and hence their serological
markers must be determined. The aim of this study was to evaluate the prevalence
of serological markers of HAV and HBV infection in patients with chronic HCV.
MATERIAL AND METHODS: One thousand chronic HCV patients at the University of Sao
Paulo School of Medicine were evaluated for the prevalence of serological markers
of HAV and HBV infection. RESULTS: Anti-HAV IgG was positive in 92.3% of
patients. When stratified by age, anti-HAV IgG was found in 61% of patients
between 20-29 years, 70% on patients between 30-39 years, 85% on patients between
40-49 years, 94% on patients between 50-59 years, and in 99% on patients over 60
years of age. Anti-HBc IgG was positive in 244 patients (24%). Stratified by age,
in 4.3% of patients between 20-29 years, 17% 30-39 years, 21% 40-49 years, 24% 50
59 years, and in 28% of patients over 60 years. Of the 244 anti-HBc IgG positive
patients, 0.8% were HBsAg positive, 8.5% were anti-HBc IgG isolated and 16% were
also anti-HBs positive. CONCLUSIONS: In conclusion, the prevalence of anti-HAV
IgG was similar to the general Brazilian population. However, anti-HBc IgG was
higher in our patients, when compared to general population of Western countries,
emphasizing the importance of immunization programs for this population.
PMID- 27493108
TI - Resistance-associated polymorphisms in Dutch hepatitis C genotype 1a patients
with and without HIV infection.
AB - Background and aim. Resistance-associated variants (RAVs) on the NS3 region of
the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in
human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed
frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without
HIV coinfection. MATERIAL AND METHODS: HCV NS3 amino acids 1-181 were sequenced
by the Sanger method and analyzed for RAVs. RAVs and their distribution between
HCV genotype 1a clade I and II viruses were compared between HIV-infected versus
HIV-uninfected patients. RESULTS: 148 samples were available (n = 68 HIV and n =
80 non-HIV). Relative frequency of clade I and clade II was significantly
different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall,
HIV infected patients exhibited significantly lower prevalence of RAVs than HIV
uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was
significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas
prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p <
0.0001) polymorphisms were significantly lower. Q80K was found exclusively in
clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001)
polymorphisms had significantly lower prevalence in clade I than clade II
viruses. CONCLUSIONS: In the Netherlands, prevalence of clade I viruses and Q80K
was significantly higher in HCV genotype 1a infected patients with HIV
coinfection than in those without HIV coinfection. Prevalence of N174 and S122
polymorphisms was significantly higher in clade II than clade I viruses.
PMID- 27493109
TI - Vaspin, resistin, retinol-binding protein-4, interleukin-1alpha and interleukin
6 in patients with nonalcoholic fatty liver disease.
AB - Background and rational. Data on newer adipokines and interleukins in patients
with nonalcoholic fatty liver disease (NAFLD) are inconclusive. The primary aim
of this study was the evaluation of serum vaspin, resistin, retinol-binding
protein (RBP)-4, interleukin (IL)-1alpha and IL-6 levels in NAFLD patients
compared to matched controls, and their association with disease severity.
MATERIAL AND METHODS: Twenty-nine consecutively enrolled NAFLD patients with
histologically confirmed nonalcoholic simple steatosis (SS; n = 15) or
steatohepatitis (NASH; n = 14) and 25 matched controls without NAFLD were
recruited. Serum vaspin, resistin, RBP-4, IL-1alpha and IL-6 and biochemical
tests were measured. RESULTS: Serum vaspin levels were lower and IL-6 levels
higher in NASH patients than controls, but similar between controls and SS
patients, or NASH and SS patients (vaspin, controls: 728.5 +/- 39.3; SS: 634.6 +/
63.7; NASH: 531.5 +/- 52.0 pg/mL; p for trend 0.028; IL-6, controls: 1.5 +/-
0.2; SS: 2.5 +/- 0.6; NASH: 3.0 +/- 0.6 pg/mL; p for trend 0.032). However, after
adjustment for body mass index or waist circumference, both vaspin and IL-6 did
not remain significantly different between groups. Resistin, RBP-4 and IL-1alpha
were not statistically different between groups. None of the selected adipokines
or interleukins could independently differentiate NAFLD from SS, or patients with
more severe from less severe histological lesions. CONCLUSION: Lower circulating
vaspin, but higher IL-6 levels were observed in NASH patients than controls,
whereas resistin, RBP-4 and IL-1alpha levels were similar between groups.
However, these differences did not remain robust after adjustment for body mass
index or waist circumference.
PMID- 27493110
TI - The product of triglycerides and glucose as biomarker for screening simple
steatosis and NASH in asymptomatic women.
AB - Introduction and aim. Given that early identification of non-alcoholic fatty
liver disease (NAFLD) is an important issue for primary prevention of hepatic
disease, the objectives of this study were to evaluate the efficacy of the
product of triglyceride and glucose levels (TyG) for screening simple steatosis
and non-alcoholic steatohepatitis (NASH) in asymptomatic women, and to compare
its efficacy vs. other biomarkers for recognizing NAFLD. MATERIAL AND METHODS:
Asymptomatic women aged 20 to 65 years were enrolled into a cross-sectional
study. The optimal values of TyG, for screening simple steatosis and NASH were
established on a Receiver Operating Characteristic scatter plot; the sensitivity,
specificity, and likelihood ratios of TyG index were estimated versus liver
biopsy. According sensitivity and specificity, the efficacy of TyG was compared
versus the well-known clinical biomarkers for recognizing NAFLD. RESULTS: A total
of 50 asymptomatic women were enrolled. The best cutoff point of TyG for
screening simple steatosis was 4.58 (sensitivity 0.94, specificity 0.69); in
addition, the best cutoff point of TyG index for screening NASH was 4.59
(sensitivity 0.87, specificity 0.69). The positive and negative likelihood ratios
were 3.03 and 0.08 for simple steatosis, and 2.80 and 0.18 for NASH. As compared
versus SteatoTest, NashTest, Fatty liver index, and Algorithm, the TyG showed to
be the best test for screening. CONCLUSIONS: TyG has high sensitivity and low
negative likelihood ratio; as compared with other clinical biomarkers, the TyG
showed to be the best test for screening simple steatosis and NASH.
PMID- 27493111
TI - High prevalence of undiagnosed liver cirrhosis and advanced fibrosis in type 2
diabetic patients.
AB - Background. Patients with type 2 diabetes mellitus (T2DM) are at risk for
developing end-stage liver disease due to nonalcoholic steatohepatitis (NASH),
the aggressive form of non-alcoholic fatty liver disease (NAFLD). Data on
prevalence of advanced fibrosis among T2DM patients is scarce. AIM: To evaluate
prevalence of steatosis, advanced fibrosis and cirrhosis using non-invasive
methods in T2DM patients. MATERIAL AND METHODS: 145 consecutive T2DM patients (>
55 years-old) were prospectively recruited. Presence of cirrhosis and advanced
fibrosis was evaluated by magnetic resonance imaging (MRI) and NAFLD fibrosis
score (NFS) respectively. Exclusion criteria included significant alcohol
consumption, markers of viral hepatitis infection or other liver diseases.
Results are expressed in percentage or median (interquartile range). RESULTS:
52.6% of patients were women, the median age was 60 years old (57-64), mean BMI
was 29.6 +/- 4.7 kg/m2 and diabetes duration was 7.6 +/- 6.9 years. A high
prevalence of liver steatosis (63.9%), advanced fibrosis assessed by NFS (12.8%)
and evidence of liver cirrhosis in MRI (6.0%) was observed. In a multivariate
analysis GGT > 82 IU/L (P = 0.004) and no alcohol intake (P = 0.032) were
independently associated to advanced fibrosis. CONCLUSION: A high frequency of
undiagnosed advanced fibrosis and cirrhosis was observed in non-selected T2DM
patients. Screening of these conditions may be warranted in this patient
population.
PMID- 27493113
TI - Schistosomal portal hypertension: Randomized trial comparing endoscopic therapy
alone or preceded by esophagogastric devascularization and splenectomy.
AB - Background. Upper gastrointestinal bleeding is a major cause of morbidity and
mortality in patients with portal hypertension secondary to schistosomiasis
mansoni. AIM: To evaluate the efficacy of combined surgery and sclerotherapy
versus endoscopic treatment alone in the prophylaxis of esophageal variceal
rebleeding due to portal hypertension in schistosomiasis. MATERIAL AND METHODS:
During a two-years period consecutive patients with schistosomiasis and a recent
bleeding history were evaluated for prospective randomization. Absolute exclusion
criteria were alcoholism or other liver diseases, whereas platelet count <
50,000/mm3, INR > 1.5 or presence of gastric varices were relative exclusion
criteria. By random allocation 25 (group A) have received endoscopic
sclerotherapy for esophageal varices alone and 22 (group B) combined treatment:
esophagogastric devascularization with splenectomy followed by sclerotherapy.
Interim analysis at 24 months has shown significant statistical differences
between the groups and the randomization was halted. RESULTS: Mean age was 38.9
+/- 15.4 years and 58.46% were male. Mean follow-up was 38.6 +/- 20.1 months.
Endoscopic comparison of the size of esophageal varices before and after
treatment did not show significant differences among the two groups. Treatment
efficacy was assessed by the rate of recurrent esophageal variceal bleeding, that
was more common in group A- 9/25 patients (36.0%) vs. 2/22 (9.0%) in group B (p =
0.029). Other complications were odynophagia, dysphagia and esophageal ulcer in
group A and ascites and portal vein thrombosis in the surgical group. CONCLUSION:
In portal hypertension due to schistosomiasis, combined surgical and endoscopic
treatment was more effective for the prevention of recurrent esophageal variceal
bleeding.
PMID- 27493112
TI - Effects of combined genes of CTLA4Ig and IDO in post-liver transplantation
immune tolerance of rats.
AB - Background and rationale for the study. Previous studies showed that CTLA4Ig and
indoleamine 2,3-dioxygenase (IDO) genes played regulatory role in organ
transplantation but failed to reach satisfactory effects. In this study, we
constructed an adenovirus- mediated gene expressing CTLA4Ig-IDO and established
rat liver transplantation models. Recipients were randomly divided into four
groups of 10 rats each. During the operation, CTLA4Ig, IDO, and CTLA4Ig-IDO
genes, as well as a blank plasmid, were infused into different rat groups via
portal vein to determine their effects on inducing immune tolerance. Survival
rate of recipients, histological changes of graft liver, post-transplantation
liver function, and cytokine levels were observed at day 14 after operation.
RESULTS: Serum levels of alanine aminotransferase (ALT), aspartate transaminase
(AST), and total bilirubin level (TBIL) in the CTLA4Ig-IDO group were lower than
those in the other three groups at 14 days post-transplantation (P < 0.05); mRNA
and protein expressions of IL-2 and IFN-gamma were higher in the control group,
but lower in the CTLA4Ig-IDO group (P < 0.05). By contrast, expressions of IL-4,
TGF-b, IL-10, and T lymphocyte apoptosis were higher in the CTLA4Ig-IDO group
than those in the other three groups (P < 0.05). The CTLA4Ig-IDO group exhibited
mild acute rejection and higher survival rate compared with the other groups (P <
0.05). CONCLUSION: Compared with using CTLA4Ig or IDO alone, combined
transfection of CTLA4Ig-IDO was more effective in inducing immune tolerance after
liver transplantation.
PMID- 27493114
TI - Risk factors contributing to early infection following transjugular intrahepatic
portosystemic shunt in perioperative period.
AB - Introduccion and aim. To investigate and identify the risk factors associated
with early infection following a transjugular intrahepatic portosystemic shunt
(TIPS)procedure in perioperative period. MATERIAL AND METHODS: The interventional
radiology database at the West China Hospital in Sichuan, China was reviewed to
identify all patients that underwent a TIPS procedure between January 30, 2013
and August 30, 2015. Four hundred and sixty-six TIPS patients with liver
cirrhosis were enrolled in this study. Liver function was assessed using the
Child-Pugh classification system and bacteremia was defined as patients that had
a positive blood culture. Statistical analysis was performed using chi2 tests
(include Fisher's exact tests chi2) and logistic regression analyses. A P< 0.05
was set as the threshold for statistical significance. RESULTS: One hundred and
forty-eight of the 466 (31.7%) patients developed a fever. Eighty-three of the
148 fever patients subsequently had blood drawn for cultures and 9/83 (10.8%)
patients developed bacteremia as defined by a blood culture analysis.
Cholangiolithiasis (P = 0.006), Child-Pugh class A designation (P = 0.001), Child
Pugh class C designation (P = 0.005) and hepatitis C virus infection (P = 0.011)
were significantly correlated with fever in these patients. No statistically
significant correlations were found between the other factors (age, gender,
clinical manifestation, diabetes mellitus, cholangiolithiasis, etc.) and
bacteremia, with the exception of periprocedure cholangiolithiasis, which was
significantly correlated with blood culture-defined bacteremia (P < 0.05).
CONCLUSIONS: Cholangiolithiasis is a risk factor for infection after a TIPS
procedure in the periprocedure period.
PMID- 27493115
TI - Efficacy and safety of ursodeoxycholic acid in patients with intrahepatic
cholestasis of pregnancy.
AB - Background and aims. Patients with intrahepatic cholestasis of pregnancy (ICP)
benefit from ursodeoxycholic acid (UDCA) treatment. Since there is still certain
reluctance to use UDCA in pregnant women, mainly due to warnings in the official
SPC information in respective drug leaflets, our objective was to assess the
efficacy and safety of UDCA during pregnancy. MATERIAL AND METHODS: Our
retrospective multicentric study was performed on 191 consecutive pregnant women
with ICP treated with UDCA. Any maternal and/or fetal complications of the UDCA
treatment were searched for; healthy pregnant women (n = 256) served as controls.
RESULTS: The UDCA treatment improved liver disease status in the majority of the
affected women (86.1%). This treatment was well tolerated, with only negligible
skin reactions (0.5%) and mild diarrhea (4.7%). No complications attributable to
UDCA treatment were detected during the fetal life, delivery, or the early
neonatal period. CONCLUSION: We confirmed the good efficacy and safety of UDCA
treatment in pregnancy for both mothers and fetuses/neonates.
PMID- 27493117
TI - Chilaiditi syndrome. An uncommon cause of crampy, upper abdominal pain.
PMID- 27493116
TI - Fibrin-mediated integrin signaling plays a critical role in hepatic regeneration
after partial hepatectomy in mice.
AB - Background. The regenerative capacity of the liver is critical for proper
responses to injury. Fibrin extracellular matrix (ECM) deposition is a common
response to insult and contributes to inflammatory liver injury. However, the
role of this matrix in hepatic regeneration has not been determined. OBJECTIVE:
The purpose of this study was first to determine the role of fibrin ECM in
hepatic regeneration followed by the role of the fibrin-binding alphavbeta3
integrin in mediating this effect. MATERIAL AND METHODS: C57Bl/6J (WT) or PAI-1
knockout (KO) mice underwent 70% partial hepatectomy (PHx); plasma and histologic
indices of regeneration were determined, as well as expression of key genes
involved in hepatic regeneration. RESULTS: PHx promoted transient fibrin
deposition by activating coagulation and concomitantly decreasing fibrinolysis.
Inhibiting fibrin deposition, either by blocking thrombin (hirudin) in WT mice or
by knocking out PAI-1, was associated with a decrease in hepatocyte proliferation
after PHx. This strongly suggested a role for fibrin ECM in liver regeneration.
To investigate if alphavbeta3 integrin mediates this action, we tested the
effects of the anti-alphavbeta3 cyclic peptide RGDfV in animals after PHx. As was
observed with inhibition of fibrin deposition, competitive inhibition of
alphavbeta3 integrin delayed regeneration after PHx, while not affecting fibrin
deposition. These effects of RGDfV correlated with impaired angiogenesis and
STAT3 signaling, as well as transient endothelial dysfunction. In conclusion,
these data suggest that alphavbeta3 integrin plays an important role in
coordinating hepatocyte division during liver regeneration after PHx via
crosstalk with fibrin ECM.
PMID- 27493118
TI - Early initiation of MARS(r) dialysis in Amanita phalloides-induced acute liver
injury prevents liver transplantation.
AB - Amanita phalloides is the most relevant mushroom intoxication leading to acute
liver failure. The two principal groups of toxins, the amatoxins and the
phallotoxins, are small oligopeptides highly resistant to chemical and physical
influences. The amatoxins inhibit eukaryotic RNA polymerase II causing
transcription arrest affecting mainly metabolically highly active cells like
hepatocytes and renal cells. The clinically most characteristic symptom is a 6-40
h lag phase before onset of gastrointestinal symptoms and the rapid progression
of acute liver failure leading to multi-organ failure and death within a week if
left untreated. Extracorporeal albumin dialysis (ECAD) was reported to improve
patient's outcome or facilitate bridging to transplantation. In our tertiary
center, out of nine intoxicated individuals from five non-related families six
patients presented with acute liver injury; all of them were treated with ECAD
using the MARS(r) system. Four of them were listed on admission for high urgency
liver transplantation. In addition to standard medical treatment for Amanita
intoxication we initiated ECAD once patients were admitted to our center. Overall
16 dialysis sessions were performed. All patients survived with full native liver
recovery without the need for transplantation. ECAD was well tolerated; no severe
adverse events were reported during treatment. Coagulopathy resolved within days
in all patients, and acute kidney injury in all but one individual. In
conclusion, ECAD is highly effective in treating intoxication with Amanita
phalloides. Based on these experiences we suggest early initiation and repeated
sessions depending on response to ECAD with the chance of avoiding liver
transplantation.
PMID- 27493119
TI - An unusual type of biliar cyst: A case report.
AB - We present the case of a 56-yr-old woman with vague abdominal pain of
approximately 5 months duration. An ultrasound study showed moderate dilation of
the common bile duct. Magnetic resonance cholangiopancreatography confirmed a
cystic dilatation of the right hepatic duct with intra and extra hepatic
component. The patient underwent right hepatectomy and complete excision of the
cyst. Microscopically, the cyst wall was formed by fibrous tissue with mild acute
and chronic inflammatory infiltrate, the inner surface showed a single layer of
columnar epithelium and extensive squamous metaplasia without atypia, wich
expressed p63 and high molecular weight cytoqueratin (34BE12).
PMID- 27493120
TI - Bile salt export pump deficiency disease: two novel, late onset, ABCB11
mutations identified by next generation sequencing.
AB - Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of
autosomal recessive cholestatic diseases of childhood and represents the main
indication for liver transplantation at this age; PFIC2 involves ABCB11 gene,
that encodes the ATPdependent canalicular bile salt export pump (BSEP). Benign
intrahepatic cholestasis (BRIC) identifies a group of diseases involving the same
genes and characterized by intermittent attacks of cholestasis with no
progression to liver cirrhosis. Diagnosis with standard sequencing techniques is
expensive and available only at a few tertiary centers. We report the application
of next generation sequencing (NGS) in the diagnosis of the familial intrahepatic
cholestasis with a parallel sequencing of three causative genes. We identified
the molecular defects in ABCB11 gene in two different probands who developed a
severe cholestatic disease of unknown origin. In the first patient a compound
heterozygosity for the novel frameshift mutation p.Ser1100GlnfsX38 and the
missense variant p.Glu135Lys was detected. In the second patient, triggered by
contraceptive therapy, we identified homozygosity for a novel missense variant
p.Ala523Gly. In conclusion, these mutations seem to have a late onset and a less
aggressive clinical impact, acting as an intermediate form between BRIC and PFIC.
PMID- 27493121
TI - How to screen NAFLD patients for diabetes?
PMID- 27493122
TI - Effect of ezetimibe in HCV viral load after liver transplantation.
PMID- 27493123
TI - Cell-based therapy to reverse advanced alcoholic liver fibrosis.
PMID- 27493124
TI - Different interactomes for p70-S6K1 and p54-S6K2 revealed by proteomic analysis.
AB - S6Ks are major effectors of the mTOR (mammalian target of rapamycin) pathway,
signaling for increased protein synthesis and cell growth in response to insulin,
AMP/ATP levels, and amino acids. Deregulation of this pathway has been related to
disorders and diseases associated with metabolism, such as obesity, diabetes, and
cancer. S6K family is composed of two main members, S6K1 and S6K2, which comprise
different isoforms resulted from alternative splicing or alternative start codon
use. Although important molecular functions have been associated with p70-S6K1,
the most extensively studied isoform, the S6K2 counterpart lacks information. In
the present study, we performed immunoprecipitation assays followed by mass
spectrometry (MS) analysis of FLAG-tagged p70-S6K1 and p54-S6K2 interactomes,
after expression in HEK293 cells. Protein lists were submitted to CRAPome
(Contaminant Repository for Affinity Purification) and SAINT (Significance
Analysis of INTeractome) analysis, which allowed the identification of high
scoring interactions. By a comparative approach, p70-S6K1 interacting proteins
were predominantly related to "cytoskeleton" and "stress response," whereas p54
S6K2 interactome was more associated to "transcription," "splicing," and
"ribosome biogenesis." Moreover, we have found evidences for new targets or
regulators of the S6K protein family, such as proteins NCL, NPM1, eIF2alpha,
XRCC6, PARP1, and ILF2/ILF3 complex. This study provides new information about
the interacting networks of S6Ks, which may contribute for future approaches to a
better understanding of the mTOR/S6K pathway.
PMID- 27493125
TI - Synthesis of surface-modified TREN-cored PAMAM dendrimers and their effects on
the solubility of sulfamethoxazole (SMZ) as an analog antibiotic drug.
AB - Sulfamethoxazole (SMZ) is a sulfonamide and used widely in the treatment of
bacteriostatic and urinary tract infections with trimethoprim as an antibiotic.
The problem with SMZ is its poor water solubility, therefore, low bioavailability
in clinical applications. In this study, we synthesized new-generation Tris(2
aminoethyl)amine (TREN)-cored amine (NH2), Tris(hydroxymethyl)aminomethane
(TRIS), and carboxyl (COOH) terminated different generations T2-T4
poly(amidoamine) PAMAM dendrimers. Synthesized PAMAMs were characterized by 1H
NMR, 13C NMR, ATR-FTIR, spectroscopic titrations, and evaluated as potential
solubility enhancers and drug carriers of sulfonamides by taking SMZ as a model
drug. The effect of concentration, generation, and surface groups of PAMAMs on
the solubility of SMZ was also investigated. Results showed that the solubility
of SMZ improved significantly with an increasing generation size (T2-T4) and
PAMAM dendrimer concentration (0-2 mM). The role of PAMAMs in the solubility
enhancement of SMZ was in the order of T4.NH2 > T4.COOH > T3.NH2 > T4.TRIS >
T2.NH2 > T3.COOH > T3.TRIS > T2.COOH > T2.TRIS, and in the ranges of 5- to 45
fold with maximum SMZ loading 7 to 61 mole/mole per PAMAM dendrimer molecule. In
vitro release studies demonstrated that SMZ-PAMAM dendrimer complexes at the end
of 2-h drug release (16-26%) was considerable slower than pure SMZ (38.8%).
PMID- 27493126
TI - Three-dimensional transesophageal echocardiography incremental value in a rare
case of a bileaflet tricuspid valve.
AB - Detailed assessment of the tricuspid valve using two-dimensional echocardiography
is always challenging, as only two of three leaflets can be seen at a time. Three
dimensional echocardiography can provide the enface view of the tricuspid valve
that allows simultaneous visualization of all of the three leaflets. In a 42-year
old male patient scheduled for pulmonary endarterectomy, 3DTEE showed that the
tricuspid valve is bileaflet, with one septal and another lateral leaflet. There
were two commissures, one of them is anteriorly positioned and the other one is
posterior. Our findings were confirmed intra-operatively by direct surgical
visualization of the tricuspid valve.
PMID- 27493128
TI - Fungal prosthetic valve endocarditis with mycotic aneurysm: Case report.
AB - Fungal prosthetic valve endocarditis is an extremely severe form of infective
endocarditis, with poor prognosis and high mortality despite treatment. Candida
albicans is the most common etiological agent for this rare but increasingly
frequent condition. We present a case of fungal prosthetic valve endocarditis due
to C. albicans following aortic and pulmonary valve replacement in a 38-year-old
woman with a history of surgically corrected tetralogy of Fallot, prior infective
endocarditis and acute renal failure with need for catheter-based hemodialysis.
Antifungal therapy with liposomal amphotericin B was initiated prior to cardiac
surgery, in which the bioprostheses were replaced by homografts, providing
greater resistance to recurrent infection. During hospitalization, a mycotic
aneurysm was diagnosed following an episode of acute arterial ischemia, requiring
two vascular surgical interventions. Despite the complications, the patient's
outcome was good and she was discharged on suppressive antifungal therapy with
oral fluconazole for at least a year. The reported case illustrates multiple risk
factors for fungal endocarditis, as well as complications and predictors of poor
prognosis, demonstrating its complexity.
PMID- 27493127
TI - Dehydration of Glucose to 5-Hydroxymethylfurfural Using Nb-doped Tungstite.
AB - Dehydration of glucose to 5-hydroxymethylfurfural (HMF) remains a significant
problem in the context of the valorization of lignocellulosic biomass. Hydrolysis
of WCl6 and NbCl5 leads to precipitation of Nb-containing tungstite (WO3 ?H2 O)
at low Nb content and mixtures of tungstite and niobic acid at higher Nb content.
Tungstite is a promising catalyst for the dehydration of glucose to HMF. Compared
with Nb2 O5 , fewer by-products are formed because of the low Bronsted acidity of
the (mixed) oxides. In water, an optimum yield of HMF was obtained for Nb-W
oxides with low Nb content owing to balanced Lewis and Bronsted acidity. In
THF/water, the strong Lewis acidity and weak Bronsted acidity caused the reaction
to proceed through isomerization to fructose and dehydration of fructose to a
partially dehydrated intermediate, which was identified by LC-ESI-MS. The
addition of HCl to the reaction mixture resulted in rapid dehydration of this
intermediate to HMF. The HMF yield obtained in this way was approximately 56 %
for all tungstite catalysts. Density functional theory calculations show that the
Lewis acid centers on the tungstite surface can isomerize glucose into fructose.
Substitution of W by Nb lowers the overall activation barrier for glucose
isomerization by stabilizing the deprotonated glucose adsorbate.
PMID- 27493129
TI - Examining the relationship between antihypertensive medication satisfaction and
adherence in older patients.
AB - BACKGROUND: The relationship between medication adherence and treatment
satisfaction has been consistently positive, however, this relationship has not
been examined among older adults with hypertension. OBJECTIVES: The aim of this
study was to examine the relationship between medication adherence and treatment
satisfaction among a sample of older adults with hypertension. METHODS: This was
a survey-based cross-sectional study in which seven community senior centers in
the city of Memphis, Tennessee and its surrounding areas were visited.
Individuals aged 60 years and older with self-reported hypertension who visited
the community senior centers between August and December 2013 were asked to
participate. The participants' satisfaction with their antihypertensive
medications was assessed using a newly developed scale. The Short Form Health
Survey (SF-12v2) was used to assess the health-related quality of life (HRQoL).
The Primary Care Assessment Survey (PCAS) Communication scale was used to assess
the satisfaction with health care provider communication. The Beliefs About
Medicines Questionnaire (BMQ-General) was used to assess the participant beliefs
about medications. The eight-item Morisky Medication Adherence Scale (MMAS-8) was
used to assess adherence to antihypertensive medications. And the Single Item
Literacy Screener (SILS) was used to assess health literacy. Multiple linear
regression was conducted to examine the relationship between medication adherence
and satisfaction with antihypertensive therapy controlling for multiple
variables. RESULTS: One hundred and ninety participants with hypertension were
included in the study. Most participants were white, women, aged >=70 years,
taking >=2 prescription medications and having >=2 medical conditions. After
adjusting for age, education, number of prescription medications, race, health
literacy, sex, marital status, SF-12v2 Physical Component Summary (PCS-12) and
Mental Component Summary (MCS-12), and PCAS-Communication scores, the overall
satisfaction score of the antihypertensive medication regimen was positively and
significantly associated with MMAS-8 sore (beta = 0.262; 95% confidence interval,
0.007-0.517; P = 0.043). CONCLUSIONS: Treatment satisfaction was associated with
higher medication adherence among older adults with hypertension.
PMID- 27493130
TI - Challenges in pediatric drug use: A pharmacist point of view.
AB - The pediatric population is an enormously diverse segment of population varying
both in size and age. The diversity caused pharmacists face various challenges
primarily related to procuring, provision as well as use of drugs in this group
of patients. Pediatric dose calculation is particularly a concern for
pharmacists. Another challenge faced by pharmacists is unavailability of suitable
formulations for pediatric use. This has also led many pharmacists to prepare
extemporaneous liquid preparations, even though stability data on such
preparations are scarce. Some extemporaneous preparations contain excipients
which are potentially harmful in children. Besides that, inadequate labeling and
drug information for pediatric drug use had not only challenged pharmacists in
recommending and optimizing drug use in children, but also inadvertently caused
many drugs used outside the approved terms of the product license (off-label
use). Pharmacists are striving to stay connected to overcome the common and
comparable challenges faced in their day to day duties and strive to maximize the
safe and effective use of medicines for children.
PMID- 27493132
TI - Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects
With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial.
AB - OBJECTIVE: To investigate the efficacy and safety of liraglutide added to capped
insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A 26
week, placebo-controlled, double-blind, parallel-group trial enrolling 835
subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2,
and 0.6 mg) or placebo added to an individually capped total daily dose of
insulin. RESULTS: Mean baseline glycated hemoglobin (HbA1c) (8.1% [65.0
mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26
(1.8 mg: -0.33% [3.6 mmol/mol]; 1.2 mg: -0.22% [2.4 mmol/mol]; 0.6 mg: -0.23%
[2.5 mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced
mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively)
versus placebo (-0.2 kg). Significant reductions in daily insulin dose and
increases in quality of life were seen with liraglutide versus placebo. There
were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year;
P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis
>1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year;
P = 0.01). CONCLUSIONS: In a broad population of subjects with long-standing type
1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and
insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg
and hyperglycemia with ketosis for liraglutide 1.8 mg.
PMID- 27493133
TI - Impact of the Gather mHealth System on A1C: Primary Results of a Multisite
Randomized Clinical Trial Among People With Type 2 Diabetes in India.
PMID- 27493131
TI - The Platin-X series: activation, targeting, and delivery.
AB - Anticancer platinum (Pt) complexes have long been considered to be one of the
biggest success stories in the history of medicinal inorganic chemistry. Yet
there remains the hunt for the "magic bullet" which can satisfy the requirements
of an effective chemotherapeutic drug formulation. Pt(iv) complexes are
kinetically more inert than the Pt(ii) congeners and offer the opportunity to
append additional functional groups/ligands for prodrug activation, tumor
targeting, or drug delivery. The ultimate aim of functionalization is to enhance
the tumor selective action and attenuate systemic toxicity of the drugs.
Moreover, an increase in cellular accumulation to surmount the resistance of the
tumor against the drugs is also of paramount importance in drug development and
discovery. In this review, we will address the attempts made in our lab to
develop Pt(iv) prodrugs that can be activated and delivered using targeted
nanotechnology-based delivery platforms.
PMID- 27493134
TI - Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks
Analysis.
AB - OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to
assess the association between diabetes and cause-specific death. RESEARCH DESIGN
AND METHODS: We used the pooled analysis of individual data from 12 Spanish
population cohorts with 10-year follow-up. Participants had no previous history
of cardiovascular diseases and were 35-79 years old. Diabetes status was self
reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes
of death were ascertained by medical records review and linkage with the official
death registry. The hazard ratios and cumulative mortality function were assessed
with two approaches, with and without competing risks: proportional
subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively.
Multivariate analyses were fitted for cardiovascular, cancer, and
noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals
(15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios
showed that diabetes increased mortality risk: 1) cardiovascular death, CSH =
2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75
2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13
1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH =
1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53
(1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH
= 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function
was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is
associated with premature death from cardiovascular disease, cancer, and
noncardiovascular noncancer causes. The use of CSH and PSH provides a
comprehensive view of mortality dynamics in a population with diabetes.
PMID- 27493137
TI - Isolation and characterization of atypical Listeria monocytogenes associated with
a canine urinary tract infection.
AB - Listeria monocytogenes, a well-described cause of encephalitis and abortion in
ruminants and of food-borne illness in humans, is rarely associated with disease
in companion animals. A case of urinary tract infection associated with an
atypical, weakly hemolytic L. monocytogenes strain is described in a diabetic
dog. The serotype of the L. monocytogenes isolate was determined to be 1/2a (3a),
with the multilocus genotyping pattern 2.72_1/2a. A nucleotide substitution
(Gly145Asp) was detected at residue 145 in the promoter prfA region. This residue
is within the critical helix-turn-helix motif of PrfA. The source of the L.
monocytogenes strain remains unknown, and the dog recovered after a 4-week course
of cephalexin (30 mg/kg orally twice daily).
PMID- 27493135
TI - Effect of Serotonin Transporter 5-HTTLPR Polymorphism on Gastrointestinal
Intolerance to Metformin: A GoDARTS Study.
AB - OBJECTIVE: The mechanism causing gastrointestinal intolerance to metformin
treatment is unknown. We have previously shown that reduced-function alleles of
organic cation transporter 1 (OCT1) are associated with increased intolerance to
metformin. Considering recent findings that serotonin reuptake transporter (SERT)
might also be involved in metformin intestinal absorption, and the role of
serotonin in gastrointestinal physiology, in this study we investigated the
association between a common polymorphism in the SERT gene and metformin
gastrointestinal intolerance. RESEARCH DESIGN AND METHODS: We explored the effect
of composite SERT 5-HTTLPR/rs25531 genotypes, L*L* (LALA), L*S* (LALG, LAS), and
S*S* (SS, SLG, LGLG), in 1,356 fully tolerant and 164 extreme metformin
intolerant patients by using a logistic regression model, adjusted for age, sex,
weight, OCT1 genotype, and concomitant use of medications known to inhibit OCT1
activity. RESULTS: The number of low-expressing SERT S* alleles increased the
odds of metformin intolerance (odds ratio [OR] 1.31 [95% CI 1.02-1.67], P =
0.031). Moreover, a multiplicative interaction between the OCT1 and SERT
genotypes was observed (P = 0.003). In the analyses stratified by SERT genotype,
the presence of two deficient OCT1 alleles was associated with more than a
ninefold higher odds of metformin intolerance in patients carrying the L*L*
genotype (OR 9.25 [95% CI 3.18-27.0], P < 10-4); however, it showed a much
smaller effect in L*S* carriers and no effect in S*S* carriers. CONCLUSIONS: Our
results indicate that the interaction between OCT1 and SERT genes might play an
important role in metformin intolerance. Further studies are needed to replicate
these findings and to substantiate the hypothesis that metformin gastrointestinal
side effects could be related to the reduced intestinal serotonin uptake.
PMID- 27493136
TI - Initial Combination of Empagliflozin and Metformin in Patients With Type 2
Diabetes.
AB - OBJECTIVE: This study compared the efficacy and safety of initial combinations of
empagliflozin + metformin with empagliflozin and metformin monotherapy in
patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The study randomized
1,364 drug-naive patients (HbA1c >7.5 to <=12% [>58 to <=108 mmol/mol]) for 24
weeks to empagliflozin 12.5 mg b.i.d. + metformin 1,000 mg b.i.d., empagliflozin
12.5 mg b.i.d. + metformin 500 mg b.i.d., empagliflozin 5 mg b.i.d + metformin
1,000 mg b.i.d., empagliflozin 5 mg b.i.d. + metformin 500 mg b.i.d.,
empagliflozin 25 mg q.d., empagliflozin 10 mg q.d., metformin 1,000 mg b.i.d., or
metformin 500 mg b.i.d. The primary end point was change from baseline in HbA1c
at week 24. RESULTS: At week 24, reductions in HbA1c (mean baseline 8.6-8.9% [70
73 mmol/mol]) were -1.9 to -2.1% with empagliflozin + metformin twice-daily
regimens, -1.4% with both empagliflozin once-daily regimens, and -1.2 to -1.8%
with metformin twice-daily regimens. Reductions in HbA1c were significantly
greater with empagliflozin + metformin twice-daily regimens than with
empagliflozin once-daily regimens (P < 0.001) and with metformin twice-daily
regimens (P < 0.01). Reductions in weight at week 24 were significantly greater
with empagliflozin + metformin twice-daily regimens (range -2.8 to -3.8 kg) than
with metformin twice-daily regimens (-0.5 to -1.3 kg) (P < 0.001 for all).
Adverse event (AE) rates were similar across groups (56.7-66.3%). No hypoglycemic
AEs required assistance. CONCLUSIONS: Initial combinations of empagliflozin +
metformin for 24 weeks significantly reduced HbA1c versus empagliflozin once
daily and metformin twice daily, without increased hypoglycemia, reduced weight
versus metformin twice daily, and were well tolerated.
PMID- 27493138
TI - Rapid detection of Porcine circovirus 2 by recombinase polymerase amplification.
AB - Porcine circovirus-associated disease, caused primarily by Porcine circovirus 2
(PCV-2), has become endemic in many pig-producing countries and has resulted in
significant economic losses to the swine industry worldwide. Tests for PCV-2
infection include PCR, nested PCR, competitive PCR, and real-time PCR (rtPCR).
Recombinase polymerase amplification (RPA) has emerged as an isothermal gene
amplification technology for the molecular detection of infectious disease
agents. RPA is performed at a constant temperature and therefore can be carried
out in a water bath. In addition, RPA is completed in ~30 min, much faster than
PCR, which usually takes >60 min. We developed a RPA-based method for the
detection of PCV-2. The detection limit of RPA was 10(2) copies of PCV-2 genomic
DNA. RPA showed the same sensitivity as rtPCR but was 10 times more sensitive
than conventional PCR. Successful amplification of PCV-2 DNA, but not other viral
templates, demonstrated high specificity of the RPA assay. This method was also
validated using clinical samples. The results showed that the RPA assay had a
diagnostic agreement rate of 93.7% with conventional PCR and 100% with rtPCR.
These findings suggest that the RPA assay is a simple, rapid, and cost-effective
method for PCV-2 detection, which could be potentially applied in clinical
diagnosis and field surveillance of PCV-2 infection.
PMID- 27493139
TI - A renal adenocarcinoma in a corn snake (Pantherophis guttatus) resembling human
collecting duct carcinoma.
AB - A 5-year-old male captive corn snake (Pantherophis guttatus) with caudal coelomic
swelling was admitted for surgical treatment. Laparotomy revealed a 5 * 4 * 2.5
cm, firm, expansile, irregularly shaped mass arising from the middle portion of
the right kidney with a mild lobulated pattern and mottled white-to-tan.
Microscopically, the mass was composed of numerous bizarre angulated tubules of
polygonal neoplastic cells separated by a scirrhous stroma with remarkable
heterophilic infiltrates. The neoplastic cells were nonciliated and mucin
secreting, with abundant brightly eosinophilic cytoplasm. There were marked
cellular and nuclear atypia, frequent cell individualization, and stromal
invasion, indicative of malignant behavior, which was confirmed by metastasis to
the left kidney 1.5 months postoperatively. Both neoplastic epithelial cells and
mesenchymal cells contributing to the scirrhous stroma had variable
immunopositivity for pan-cytokeratin. The neoplasm was considered a renal
adenocarcinoma resembling human collecting duct carcinoma.
PMID- 27493140
TI - Development of a loop-mediated isothermal amplification method for detecting
virulent Rhodococcus equi.
AB - Rhodococcus equi is the most important causative bacterium of severe pneumonia in
foals. We report herein the development of a specific loop-mediated isothermal
amplification (LAMP) assay, which targets a gene encoding vapA for detecting
virulent R. equi The detection limit of the LAMP assay was 10(4) colony forming
units (CFU)/mL, which was equal to 10 CFU/reaction. The clinical efficacy of the
LAMP assay was compared with those of 2 published PCR-based methods: nested PCR
and quantitative real-time (q)PCR. Agreements between bacterial culture, which is
the gold standard for detection of R. equi, and each of the 3 molecular tests
were measured by calculating a kappa coefficient. The kappa coefficients of the
LAMP (0.760), nested PCR (0.583), and qPCR (0.888) indicated substantial
agreement, moderate agreement, and almost perfect agreement, respectively.
Although the clinical efficacy of LAMP was not the best among the 3 methods
tested, LAMP could be more easily introduced into less well-equipped clinics
because it does not require special equipment (such as a thermocycler) for gene
amplification. Veterinary practitioners could diagnose R. equi pneumonia more
quickly by using LAMP and could use the results to select an appropriate initial
treatment.
PMID- 27493141
TI - Rice-produced MSP142 of Plasmodium falciparum elicits antibodies that inhibit
parasite growth in vitro.
AB - Many malaria antigens contain multiple disulphide bonds involved in the formation
of inhibitory B-cell epitopes. Producing properly folded malaria antigens in
sufficient quantities for vaccination is often a challenge. The 42-kDa fragment
of Plasmodium falciparum merozoite surface protein 1 (MSP142 ) is such a kind of
malaria antigen. In this study, we investigated the expression of MSP142 in a
rice system (9522, a cultivar of Oryza sativa ssp. japonica), which was used as a
bioreactor for protein production. The MSP142 gene was synthesized according to
rice-preferred codons and transformed into rice plants via an Agrobacterium
mediated method. The recombinant antigen was efficiently expressed in rice seeds
with a level up to 1.56% of total soluble protein and was recognized by both the
conformational monoclonal antibody 5.2 (mAb5.2) and the pooled sera of P.
falciparum malaria patients. Rabbits were immunized intramuscularly with the
purified MSP142 formulated with Freund's adjuvant. High antibody titres against
MSP142 were elicited. The rabbit immune sera reacted well with the native protein
of P. falciparum parasite and strongly inhibited the in vitro growth of blood
stage P. falciparum parasites, demonstrating that transgenic rice can become an
efficient bioreactor for the production of malaria vaccine antigens.
PMID- 27493142
TI - Genetic determinants and postorthodontic external apical root resorption in Czech
children.
AB - OBJECTIVE: Genes, involved in the modulation of inflammatory response and bone
remodeling, play a role in the development of postorthodontic external apical
root resorption (EARR). The aim of our study was to analyze possible associations
between seven single nucleotide polymorphisms (SNPs) in interleukin-17A (IL-17),
osteopontin (SPP1), purinoreceptor P2X7 (P2RX7), and tumor necrosis factor
receptor superfamily member 11B (TNFRSF11B) genes and EARR in children after
orthodontic treatment. SUBJECTS AND METHODS: This case-control study comprised 99
orthodontically treated patients (69 controls and 30 subjects with EARR).
Genotype determinations of rs2275913, rs11730582, rs9138, rs208294, rs1718119,
rs3102735, and rs2073618 were based on polymerase chain reaction using 5'
nuclease TaqMan(r) assays. RESULTS: While no significant differences were
observed in allele or genotype frequencies of all seven studied SNPs, specific
haplotype of P2RX7 (rs208294 and rs1718119) modified the risk of EARR development
(P < 0.05). In addition, the length of treatment with a fixed orthodontic
appliance positively correlated with the presence of EARR (P < 0.05).
CONCLUSIONS: Although the effect of individual SNPs studied on the EARR
development was not confirmed in the Czech population, complex analysis suggested
that variability in the P2RX7 gene and the length of orthodontic treatment may be
important factors contributing to the etiopathogenesis of postorthodontic EARR.
PMID- 27493144
TI - Calciotropic and phosphaturic hormones in heart failure.
AB - AIMS: Despite adherence to evidence-based guidelines, heart failure [HF] still
results in 5-year mortality rates of 50%, indicating a need to implement
additional preventive/intervention strategies. This review summarizes data on
alterations in the calciotropic and phosphaturic hormones 1,25-dihydroxyvitamin D
[1,25(OH)2D] and fibroblast growth factors-23 [FGF-23] in HF and discusses non
pharmacological measures for targeting these hormones. DATA SYNTHESIS: The role
of 1,25(OH)2D in the regulation of calcium and phosphate homeostasis is central.
1,25(OH)2D also plays a pivotal role in cardiac function, but is downregulated by
FGF-23. There is accumulating evidence from epidemiological data that HF is
associated with decreased circulating 1,25(OH)2D and elevated FGF-23 levels. In
patients with failing hearts, very low 1,25(OH)2D and extremely high FGF-23
levels have been reported. Experimental data support the assumption that vitamin
D deficiency and high serum phosphate/FGF-23 levels increase the risk of HF. This
review provides a hypothesis of how vitamin D deficiency, high calcium/phosphorus
intake, physical inactivity, and age-related renal impairment may all contribute
to HF by adversely affecting calcium- and phosphate-regulating hormones. Several
case series in infants and a meta-analysis of randomized controlled trials in
adults have already reported successful treatment of or a significant risk
reduction in HF by vitamin D supplements. The association of calcium/phosphorus
intake, physical activity, or renal function with calciotropic/phosphaturic
hormones and HF is however less well documented. CONCLUSIONS: More attention
should be paid in future to the association of circulating 1,25(OH)2D and FGF-23
levels with HF and to (non-pharmacological) measures for targeting these
calciotropic/phosphaturic hormones.
PMID- 27493143
TI - Neutrophil extracellular trap formation is increased in psoriasis and induces
human beta-defensin-2 production in epidermal keratinocytes.
AB - Neutrophil extracellular traps (NETs) have been implicated in the development of
certain immune-mediated diseases, but their role in psoriasis has not been
clearly defined. Human beta-defensin-2 (HBD-2) is an important antimicrobial
peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of
NETs is increased in psoriasis and determined the effect of NETs on HBD-2
production in epidermal keratinocytes. Using fluorescent microscopy, we found
that patients with psoriasis (n = 48) had higher amount of NETotic cells in their
peripheral blood compared to healthy controls (n = 48) and patients with eczema
(n = 35). Psoriasis sera showed increased ability to induce NET formation in
control neutrophils but normal NET degradation ability. The amount of NETs in the
peripheral blood correlated with psoriasis disease severity. NETosis was also
observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore,
NETs induced HBD-2 mRNA and protein production in keratinocytes, and
immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis
lesional skin. In summary, NET formation is increased in peripheral blood and
lesional skin of psoriasis patients and correlates with disease severity.
Additionally, NET-induced HBD-2 production may provide a novel mechanism for the
decreased susceptibility of psoriasis plaques to microbial infections.
PMID- 27493145
TI - Differential hypersaline stress response in Zygosaccharomyces rouxii complex
yeasts: a physiological and transcriptional study.
AB - The Zygosaccharomyces rouxii complex comprises three distinct lineages of
halotolerant yeasts relevant in food processing and spoilage, such as Z. sapae,
Z. rouxii and a mosaic group of allodiploid strains. They manifest plastic genome
architecture (variation in karyotype, ploidy level and Na(+)/H(+) antiporter
encoding gene copy number), and exhibit diverse tolerances to salt
concentrations. Here, we investigated accumulation of compatible osmolytes and
transcriptional regulation of Na(+)/H(+) antiporter-encoding ZrSOD genes during
salt exposure in strains representative for the lineages, namely Z. sapae
ABT301(T) (low salt tolerant), Z. rouxii CBS 732(T) (middle salt tolerant) and
allodiploid strain ATCC 42981 (high salt tolerant). Growth curve modelling in 2 M
NaCl-containing media supplemented with or without yeast extract as nitrogen
source indicates that moderate salt tolerance of CBS 732(T) mainly depends on
nitrogen availability rather than intrinsic inhibitory effects of salt. All the
strains produce glycerol and not mannitol under salt stress and use two different
glycerol balance strategies. ATCC 42981 produces comparatively more glycerol than
Z. sapae and Z. rouxii under standard growth conditions and better retains it
intracellularly under salt injuries. Conversely, Z. sapae and Z. rouxii enhance
glycerol production under salt stress and intracellularly retain glycerol less
efficiently than ATCC 42981. Expression analysis shows that, in diploid Z. sapae
and allodiploid ATCC 42981, transcription of gene variants ZrSOD2-22/ZrSOD2 and
ZrSOD22 is constitutive and salt unresponsive.
PMID- 27493146
TI - Evolutionary genomics of yeast pathogens in the Saccharomycotina.
AB - Saccharomycotina comprises a diverse group of yeasts that includes numerous
species of industrial or clinical relevance. Opportunistic pathogens within this
clade are often assigned to the genus Candida but belong to phylogenetically
distant lineages that also comprise non-pathogenic species. This indicates that
the ability to infect humans has evolved independently several times among
Saccharomycotina. Although the mechanisms of infection of the main groups of
Candida pathogens are starting to be unveiled, we still lack sufficient
understanding of the evolutionary paths that led to a virulent phenotype in each
of the pathogenic lineages. Deciphering what genomic changes underlie the
evolutionary emergence of a virulence trait will not only aid the discovery of
novel virulence mechanisms but it will also provide valuable information to
understand how new pathogens emerge, and what clades may pose a future danger.
Here we review recent comparative genomics efforts that have revealed possible
evolutionary paths to pathogenesis in different lineages, focusing on the main
three agents of candidiasis worldwide: Candida albicans, C. parapsilosis and C.
glabrata We will discuss what genomic traits may facilitate the emergence of
virulence, and focus on two different genome evolution mechanisms able to
generate drastic phenotypic changes and which have been associated to the
emergence of virulence: gene family expansion and interspecies hybridization.
PMID- 27493147
TI - MRI in patients with chronic pubalgia: Is precise useful information provided to
the surgeon? A case-control study.
AB - BACKGROUND: Recent studies described that MRI is a good examination to assess
damage in chronic athletic pubalgia (AP). However, to our knowledge, no studies
focus on systematic correlation of precise tendon or parietal lesion in MRI with
surgery and histological assessment. Therefore, we performed a case-control study
to determine if MRI can precisely assess Adductor longus (AL) tendinopathy and
parietal lesion, compared with surgery and histology. HYPOTHESIS: MRI can
determine if AP comes from pubis symphysis, musculotendinous or inguinal orifice
structures. MATERIALS/METHODS: Eighteen consecutive patients were enrolled from
November 2011 to April 2013 for chronic AP. To constitute a control group, we
also enrolled 18 asymptomatic men. All MRI were reviewed in consensus by 2
skeletal radiologists for pubic symphysis, musculotendinous, abdominal wall
assessment and compared to surgery and histology findings. RESULTS: Regarding
pubis symphysis, we found 4 symmetric bone marrow oedema (14%), 2 secondary cleft
(7%) and 2 superior ligaments lesions (7%). For AL tendon, we mainly found 13
asymmetric bone marrow oedema (46%), 15 hyperaemia (54%). Regarding abdominal
wall, the deep inguinal orifice size in the group of symptomatic athletes and the
control group was respectively 27.3+/-6.4mm and 23.8+/-6.3mm. The correlation
between MRI and surgery/histology was low: 20% for the AL tendon and 9% for the
abdominal wall. If we chose the criteria "affected versus unaffected", this
correlation became higher: 100% for AL tendon and 73% for the abdominal wall.
CONCLUSION: MRI chronic athletic pubalgia concerns preferentially AL tendinopathy
and deep inguinal canal dehiscence with high correlation to surgery/histology
when only considering the item "affected versus unaffected" despite low
correlation when we try to precisely grade these lesions. LEVEL OF EVIDENCE: III:
case-control study.
PMID- 27493148
TI - Extraocular, Non-Visual, and Simple Photoreceptors: An Introduction to the
Symposium.
AB - It has been recognized for decades that animals sense light using photoreceptors
besides those that are devoted strictly to vision. However, the nature of these
receptors, their molecular components, their physiological responses, and their
biological functions are often obscure. Only recently have researchers begun to
learn how critical these non-visual or very simple visual responses are to
organismal function. New approaches, including high-throughput molecular genetic
techniques, have led to a revolution in our understanding of the evolution,
anatomical distribution, physiology, and-in some cases-function of non-visual
photoreception in diverse organisms. In the following papers, we bring together
specialists from throughout the field to review the current state of knowledge
regarding extraocular, non-visual, and simple photoreceptors in a large diversity
of organisms ranging from protists through vertebrates and invertebrates.
PMID- 27493149
TI - Microbiome Composition and Diversity of the Ice-Dwelling Sea Anemone,
Edwardsiella andrillae.
AB - Edwardsiella andrillae is a sea anemone (Cnidaria: Anthozoa: Actiniaria) only
known to live embedded in the ice at the seawater interface on the underside of
the Ross Ice Shelf, Antarctica. Although the anatomy and morphological
characteristics of E. andrillae have been described, the adaptations of this
species to the under-ice ecosystem have yet to be examined. One feature that may
be important to the physiology and ecology of E. andrillae is its microbiome,
which may play a role in health and survival, as has been deduced in other
metazoans, including anthozoans. Here we describe the microbiome of five
specimens of E. andrillae, compare the diversity we recovered to that known for
temperate anemones and another Antarctic cnidarian, and consider the phylogenetic
and functional implications of microbial diversity for these animals. The E.
andrillae microbiome was relatively low in diversity, with seven phyla detected,
yet included substantial phylogenetic novelty. Among the five anemones
investigated, the distribution of microbial taxa varied; this trait appears to be
shared by many anthozoans. Most importantly, specimens either appeared to be
dominated by Proteobacteria-affiliated members or by deeply branching Tenericute
sequences. There were few closely related sequence types that were common to
temperate and Antarctic sea anemone microbiomes, the exception being an
Acinetobacter-related representative. Similar observations were made between
microbes associated with E. andrillae and an Antarctic soft coral; however, there
were several closely-related, low abundance Gammaproteobacteria in both Antarctic
microbiomes, particularly from the soft coral, that are also commonly detected in
Southern Ocean seawater. Although this preliminary study leaves open many
questions concerning microbiome diversity and its role in host ecology, we
identify major lineages of microbes (e.g., diverse deep-branching
Alphaproteobacteria, Epsilonproteobacteria, and divergent Tenericutes affiliates)
that may play critical roles, and we highlight the current understanding and the
need for future studies of sea anemone-microbiome relationships.
PMID- 27493151
TI - Pseudoalteromonas profundi sp. nov., isolated from a deep-sea seamount.
AB - A Gram-stain-negative, rod-shaped, strictly aerobic, motile bacterial strain,
designated TP162T, was isolated from a seamount near the Yap Trench in the
tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence
showed that strain TP162T was related to the genus Pseudoalteromonas and had
highest 16S rRNA gene sequence similarities with the type strains
Pseudoalteromonas shioyasakiensis SE3T (98.2 %), Pseudoalteromonas lipolytica
LMEB 39T (97.7 %), Pseudoalteromonas arabiensis k53T (97.4 %) and
Pseudoalteromonas aliena KMM 3562T (97.2 %). The predominant cellular fatty acids
were summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1omega7c), C17 :
1omega8c and C16 : 0. The quinone system for strain TP162T comprised
predominantly ubiquinone-8, and the polar lipid profile contained
phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and
four unidentified lipids. The genomic DNA G+C content of strain TP162T was 46.7
mol%. Strain TP162T shared 28 % DNA-DNA relatedness with P.shioyasakiensis JCM
18891T, 21 % with P. lipolytica JCM 15903T, 35 % with P.arabiensis JCM 17292T and
18 % with P.aliena LMG 22059T. Combined data from phenotypic, chemotaxonomic,
phylogenetic and DNA-DNA relatedness studies demonstrated that strain TP162T is a
representative of a novel species of the genus Pseudoalteromonas, for which we
propose the name Pseudoalteromonas profundi sp. nov. (type strain TP162T=KACC
18554T=CGMCC 1.15394T).
PMID- 27493150
TI - Accessory renal arteries: Prevalence in resistant hypertension and an important
role in nonresponse to radiofrequency renal denervation.
AB - OBJECTIVE: The aim of this study was to understand the role of accessory renal
arteries in resistant hypertension, and to establish their role in nonresponse to
radiofrequency renal denervation (RDN) procedures. BACKGROUND: Prior studies
suggest a role for accessory renal arteries in hypertensive syndromes, and recent
clinical trials of renal denervation report that these anomalies are highly
prevalent in resistant hypertension. This study evaluated the relationships among
resistant hypertension, accessory renal arteries, and the response to
radiofrequency (RF) renal denervation. METHODS: Computed Tomography Angiography
(CTA) and magnetic resonance imaging (MRI) scans from 58 patients with resistant
hypertension undergoing RF renal denervation (RDN) were evaluated. Results were
compared with CT scans in 57 healthy, normotensive subjects undergoing screening
as possible renal transplant donors. All scans were carefully studied for
accessory renal arteries, and were correlated with long term blood pressure
reduction. RESULTS: Accessory renal arteries were markedly more prevalent in the
hypertensive patients than normotensive renal donors (59% vs 32% respectively,
p=0.004). RDN had an overall nonresponse rate of 29% (response rate 71%).
Patients without accessory vessels had a borderline higher response rate to RDN
than those with at least one accessory vessel (83% vs 62% respectively, p=0.076)
and a higher RDN response than patients with untreated accessory arteries (83% vs
55%; p=0.040). For accessory renal arteries and nonresponse, the sensitivity was
76%, specificity 49%, with positive and negative predictive values 38% and 83%
respectively. CONCLUSIONS: Accessory renal arteries were markedly over
represented in resistant hypertensives compared with healthy controls. While not
all patients with accessory arteries were nonresponders, nonresponse was related
to both the presence and non-treatment of accessory arteries. Addressing
accessory renal arteries in future clinical trials may improve RDN therapeutic
efficacy.
PMID- 27493152
TI - Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis.
AB - This study aimed to derive quantitative abundance values for key hepatic
transporters suitable for in vitro-in vivo extrapolation within a physiologically
based pharmacokinetic modeling framework. A meta-analysis was performed whereby
data on abundance measurements, sample preparation methods, and donor demography
were collated from the literature. To define values for a healthy Caucasian
population, a subdatabase was created whereby exclusion criteria were applied to
remove samples from non-Caucasian individuals, those with underlying disease, or
those with subcellular fractions other than crude membrane. Where a clinically
relevant active genotype was known, only samples from individuals with an
extensive transporter phenotype were included. Authors were contacted directly
when additional information was required. After removing duplicated samples, the
weighted mean, geometric mean, standard deviation, coefficient of variation, and
between-study homogeneity of transporter abundances were determined. From the
complete database containing 24 transporters, suitable abundance data were
available for 11 hepatic transporters from nine studies after exclusion criteria
were applied. Organic anion transporting polypeptides OATP1B1 and OATP1B3 showed
the highest population abundance in healthy adult Caucasians. For several
transporters, the variability in abundance was reduced significantly once the
exclusion criteria were applied. The highest variability was observed for OATP1B3
> OATP1B1 > multidrug resistance protein 2 > multidrug resistance gene 1. No
relationship was found between transporter expression and donor age. To our
knowledge, this study provides the first in-depth analysis of current
quantitative abundance data for a wide range of hepatic transporters, with the
aim of using these data for in vitro-in vivo extrapolation, and highlights the
significance of investigating the background of tissue(s) used in quantitative
transporter proteomic studies. Similar studies are now warranted for other
ethnicities.
PMID- 27493154
TI - Reading between the guidelines.
PMID- 27493153
TI - Understanding patient access patterns for primary health-care services for
Aboriginal and Islander people in Queensland: a geospatial mapping approach.
AB - This paperexplores the patterns ofpatients'accessingsix Aboriginal and Islander
CommunityControlled Health Services (AICCHSs) in Queensland. Between August 2011
and February 2014, 26199 patients made at least one visit over a 2-year period
prior to at least one of six Queensland AICCHS - one urban service (RA 1) in
south-east Queensland, and five services in regional towns (RA 3) in Far North
Queensland. Geospatial mapping of addresses for these registered patients was
undertaken. The outcomes analysed included travel times to, the proportion of
catchment populations using each AICCHS and an assessment of alternative
mainstream general practice availability to these patients was made. In brief,
the use of AICCHS was higher than Australian Bureau of Statistics census data
would suggest. Approximately 20% of clients travel more than 30min to seek
Aboriginal Health services, but only 8% of patients travelled longer than 60min.
In the major city site, many other general practitioner (GP) services were
bypassed. The data suggest Aboriginal and Islander patients in Queensland appear
to value community-controlled primary care services. The number of Indigenous
clients in regional locations in the Far North Queensland registered with
services is often higher than the estimated resident population numbers.
PMID- 27493156
TI - JIFfy Pop.
PMID- 27493158
TI - PALEONTOLOGY. Venezuela's woes hamper access to fossil trove.
PMID- 27493159
TI - BIOMEDICINE. Antiaging trial using young blood stirs concerns.
PMID- 27493155
TI - The CB1 Neutral Antagonist AM4113 Retains the Therapeutic Efficacy of the Inverse
Agonist Rimonabant for Nicotine Dependence and Weight Loss with Better
Psychiatric Tolerability.
AB - BACKGROUND: Multiple studies suggest a pivotal role of the endocannabinoid system
in regulating the reinforcing effects of various substances of abuse. Rimonabant,
a CB1 inverse agonist found to be effective for smoking cessation, was associated
with an increased risk of anxiety and depression. Here we evaluated the effects
of the CB1 neutral antagonist AM4113 on the abuse-related effects of nicotine and
its effects on anxiety and depressive-like behavior in rats. METHODS: Rats were
trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio
schedules of reinforcement. A control group was trained to self-administer food.
The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine
taking, motivation for nicotine, and cue-, nicotine priming- and yohimbine
induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal
firing and bursting activity of midbrain dopamine neurons were evaluated in a
separate group of animals treated with nicotine. Anxiety/depression-like effects
of AM4113 and rimonabant were evaluated 24h after chronic (21 days) pretreatment
(0, 1, 3, and 10mg/kg, 1/d). RESULTS: AM4113 significantly attenuated nicotine
taking, motivation for nicotine, as well as cue-, priming- and stress-induced
reinstatement of nicotine-seeking behavior. These effects were accompanied by a
decrease of the firing and burst rates in the ventral tegmental area dopamine
neurons in response to nicotine. On the other hand, AM4113 pretreatment did not
have effects on operant responding for food. Importantly, AM4113 did not have
effects on anxiety and showed antidepressant-like effects. CONCLUSION: Our
results indicate that AM4113 could be a promising therapeutic option for the
prevention of relapse to nicotine-seeking while lacking anxiety/depression-like
side effects.
PMID- 27493160
TI - U.S. RESEARCH MANAGEMENT. NSF tries two-step review, drawing praise--and darts.
PMID- 27493161
TI - INFECTIOUS DISEASE. Zika vaccine has a good shot.
PMID- 27493162
TI - SCIENCE DIPLOMACY. Synchrotron aims to bridge divides in the Middle East.
PMID- 27493163
TI - FRANCE. Dispute over president's age tears Pasteur Institute apart.
PMID- 27493164
TI - The storyteller.
PMID- 27493165
TI - The long road to LIGO.
PMID- 27493166
TI - ANTHROPOLOGY. Emperor Yu's Great Flood.
PMID- 27493167
TI - PHYSICS. Bringing order to the expanding fermion zoo.
PMID- 27493168
TI - PLANT SCIENCE. How do sunflowers follow the Sun--and to what end?
PMID- 27493169
TI - BIOTECHNOLOGY. Benefits of selective feeding.
PMID- 27493170
TI - ANALYTICAL METHODS. A nanoview of battery operation.
PMID- 27493171
TI - SCIENCE AND REGULATION. The FDA is prohibited from going germline.
PMID- 27493172
TI - NUCLEAR ENERGY. China-U.S. cooperation to advance nuclear power.
PMID- 27493173
TI - Deciphering P values: Beware false certainty.
PMID- 27493174
TI - Deciphering P values: Defining significance.
PMID- 27493175
TI - Expanding protected areas is not enough.
PMID- 27493176
TI - Comment on "Open-ocean fish reveal an omnidirectional solution to camouflage in
polarized environments".
AB - Brady et al (Reports, 20 November 2015, p. 965) claimed that the silvery sides of
certain fish are cryptic when viewed by animals with polarization sensitivity,
which they termed "polarocrypsis." After examining their evidence, we find this
claim to be unsupported due to (i) pseudoreplication, (ii) confounding
polarization contrast with intensity contrast, and (iii) measurements taken at
very shallow depths.
PMID- 27493177
TI - Response to Comment on "Open-ocean fish reveal an omnidirectional solution to
camouflage in polarized environments".
AB - Cronin et al take issue with our evidence for polarocryptic carangid fish based
on concerns of pseudoreplication, our contrast metric, and habitat. We clarify
(i) the importance of camouflage in near-surface open ocean environments and (ii)
the use of a Stokes contrast metric and further (iii) conduct individual-based
statistics on our data set to confirm the reported polarocrypsis patterns.
PMID- 27493178
TI - Grain-resolved analysis of localized deformation in nickel-titanium wire under
tensile load.
AB - The stress-induced martensitic transformation in tensioned nickel-titanium shape
memory alloys proceeds by propagation of macroscopic fronts of localized
deformation. We used three-dimensional synchrotron x-ray diffraction to image at
micrometer-scale resolution the grain-resolved elastic strains and stresses in
austenite around one such front in a prestrained nickel-titanium wire. We found
that the local stresses in austenite grains are modified ahead of the nose cone
shaped buried interface where the martensitic transformation begins. Elevated
shear stresses at the cone interface explain why the martensitic transformation
proceeds in a localized manner. We established the crossover from stresses in
individual grains to a continuum macroscopic internal stress field in the wire
and rationalized the experimentally observed internal stress field and the
topology of the macroscopic front by means of finite element simulations of the
localized deformation.
PMID- 27493179
TI - Direct conversion of methane to aromatics in a catalytic co-ionic membrane
reactor.
AB - Nonoxidative methane dehydroaromatization (MDA: 6CH4 <-> C6H6 + 9H2) using shape
selective Mo/zeolite catalysts is a key technology for exploitation of stranded
natural gas reserves by direct conversion into transportable liquids. However,
this reaction faces two major issues: The one-pass conversion is limited by
thermodynamics, and the catalyst deactivates quickly through kinetically favored
formation of coke. We show that integration of an electrochemical BaZrO3-based
membrane exhibiting both proton and oxide ion conductivity into an MDA reactor
gives rise to high aromatic yields and improved catalyst stability. These effects
originate from the simultaneous extraction of hydrogen and distributed injection
of oxide ions along the reactor length. Further, we demonstrate that the
electrochemical co-ionic membrane reactor enables high carbon efficiencies (up to
80%) that improve the technoeconomic process viability.
PMID- 27493180
TI - Origin and hysteresis of lithium compositional spatiodynamics within battery
primary particles.
AB - The kinetics and uniformity of ion insertion reactions at the solid-liquid
interface govern the rate capability and lifetime, respectively, of
electrochemical devices such as Li-ion batteries. Using an operando x-ray
microscopy platform that maps the dynamics of the Li composition and insertion
rate in Li(x)FePO4, we found that nanoscale spatial variations in rate and in
composition control the lithiation pathway at the subparticle length scale.
Specifically, spatial variations in the insertion rate constant lead to the
formation of nonuniform domains, and the composition dependence of the rate
constant amplifies nonuniformities during delithiation but suppresses them during
lithiation, and moreover stabilizes the solid solution during lithiation. This
coupling of lithium composition and surface reaction rates controls the kinetics
and uniformity during electrochemical ion insertion.
PMID- 27493181
TI - Permanent excimer superstructures by supramolecular networking of metal quantum
clusters.
AB - Excimers are evanescent quasi-particles that typically form during collisional
intermolecular interactions and exist exclusively for their excited-state
lifetime. We exploited the distinctive structure of metal quantum clusters to
fabricate permanent excimer-like colloidal superstructures made of ground-state
noninteracting gold cores, held together by a network of hydrogen bonds between
their capping ligands. This previously unknown aggregation state of matter,
studied through spectroscopic experiments and ab initio calculations, conveys the
photophysics of excimers into stable nanoparticles, which overcome the intrinsic
limitation of excimers in single-particle applications-that is, their nearly zero
formation probability in ultra-diluted solutions. In vitro experiments
demonstrate the suitability of the superstructures as nonresonant intracellular
probes and further reveal their ability to scavenge reactive oxygen species,
which enhances their potential as anticytotoxic agents for biomedical
applications.
PMID- 27493182
TI - Tuning the valley and chiral quantum state of Dirac electrons in van der Waals
heterostructures.
AB - Chirality is a fundamental property of electrons with the relativistic spectrum
found in graphene and topological insulators. It plays a crucial role in
relativistic phenomena, such as Klein tunneling, but it is difficult to visualize
directly. Here, we report the direct observation and manipulation of chirality
and pseudospin polarization in the tunneling of electrons between two almost
perfectly aligned graphene crystals. We use a strong in-plane magnetic field as a
tool to resolve the contributions of the chiral electronic states that have a
phase difference between the two components of their vector wave function. Our
experiments not only shed light on chirality, but also demonstrate a technique
for preparing graphene's Dirac electrons in a particular quantum chiral state in
a selected valley.
PMID- 27493183
TI - Outburst flood at 1920 BCE supports historicity of China's Great Flood and the
Xia dynasty.
AB - China's historiographical traditions tell of the successful control of a Great
Flood leading to the establishment of the Xia dynasty and the beginning of
civilization. However, the historicity of the flood and Xia remain controversial.
Here, we reconstruct an earthquake-induced landslide dam outburst flood on the
Yellow River about 1920 BCE that ranks as one of the largest freshwater floods of
the Holocene and could account for the Great Flood. This would place the
beginning of Xia at ~1900 BCE, several centuries later than traditionally
thought. This date coincides with the major transition from the Neolithic to
Bronze Age in the Yellow River valley and supports hypotheses that the primary
state-level society of the Erlitou culture is an archaeological manifestation of
the Xia dynasty.
PMID- 27493185
TI - Circadian regulation of sunflower heliotropism, floral orientation, and
pollinator visits.
AB - Young sunflower plants track the Sun from east to west during the day and then
reorient during the night to face east in anticipation of dawn. In contrast,
mature plants cease movement with their flower heads facing east. We show that
circadian regulation of directional growth pathways accounts for both phenomena
and leads to increased vegetative biomass and enhanced pollinator visits to
flowers. Solar tracking movements are driven by antiphasic patterns of elongation
on the east and west sides of the stem. Genes implicated in control of
phototropic growth, but not clock genes, are differentially expressed on the
opposite sides of solar tracking stems. Thus, interactions between environmental
response pathways and the internal circadian oscillator coordinate physiological
processes with predictable changes in the environment to influence growth and
reproduction.
PMID- 27493184
TI - Metabolic engineering of microbial competitive advantage for industrial
fermentation processes.
AB - Microbial contamination is an obstacle to widespread production of advanced
biofuels and chemicals. Current practices such as process sterilization or
antibiotic dosage carry excess costs or encourage the development of antibiotic
resistance. We engineered Escherichia coli to assimilate melamine, a xenobiotic
compound containing nitrogen. After adaptive laboratory evolution to improve
pathway efficiency, the engineered strain rapidly outcompeted a control strain
when melamine was supplied as the nitrogen source. We additionally engineered the
yeasts Saccharomyces cerevisiae and Yarrowia lipolytica to assimilate nitrogen
from cyanamide and phosphorus from potassium phosphite, and they outcompeted
contaminating strains in several low-cost feedstocks. Supplying essential growth
nutrients through xenobiotic or ecologically rare chemicals provides microbial
competitive advantage with minimal external risks, given that engineered
biocatalysts only have improved fitness within the customized fermentation
environment.
PMID- 27493186
TI - Macromolecular recognition directs calcium ions to coccolith mineralization
sites.
AB - Many organisms form elaborate mineralized structures, constituted of highly
organized arrangements of crystals and organic macromolecules. The localization
of crystals within these structures is presumably determined by the interaction
of nucleating macromolecules with the mineral phase. Here we show that, preceding
nucleation, a specific interaction between soluble organic molecules and an
organic backbone structure directs mineral components to specific sites. This
strategy underlies the formation of coccoliths, which are highly ordered
arrangements of calcite crystals produced by marine microalgae. On combining the
insoluble organic coccolith scaffold with coccolith-associated soluble
macromolecules in vitro, we found a massive accretion of calcium ions at the
sites where the crystals form in vivo. The in vitro process exhibits profound
similarities to the initial stages of coccolith biogenesis in vivo.
PMID- 27493187
TI - The inhibition mechanism of human 20S proteasomes enables next-generation
inhibitor design.
AB - The proteasome is a validated target for anticancer therapy, and proteasome
inhibition is employed in the clinic for the treatment of tumors and
hematological malignancies. Here, we describe crystal structures of the native
human 20S proteasome and its complexes with inhibitors, which either are drugs
approved for cancer treatment or are in clinical trials. The structure of the
native human 20S proteasome was determined at an unprecedented resolution of 1.8
angstroms. Additionally, six inhibitor-proteasome complex structures were
elucidated at resolutions between 1.9 and 2.1 angstroms. Collectively, the high
resolution structures provide new insights into the catalytic mechanisms of
inhibition and necessitate a revised description of the proteasome active site.
Knowledge about inhibition mechanisms provides insights into peptide hydrolysis
and can guide strategies for the development of next-generation proteasome-based
cancer therapeutics.
PMID- 27493189
TI - Working my way out.
PMID- 27493188
TI - RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in
ALS.
AB - Mutations in the optineurin (OPTN) gene have been implicated in both familial and
sporadic amyotrophic lateral sclerosis (ALS). However, the role of this protein
in the central nervous system (CNS) and how it may contribute to ALS pathology
are unclear. Here, we found that optineurin actively suppressed receptor
interacting kinase 1 (RIPK1)-dependent signaling by regulating its turnover. Loss
of OPTN led to progressive dysmyelination and axonal degeneration through
engagement of necroptotic machinery in the CNS, including RIPK1, RIPK3, and mixed
lineage kinase domain-like protein (MLKL). Furthermore, RIPK1- and RIPK3-mediated
axonal pathology was commonly observed in SOD1(G93A) transgenic mice and
pathological samples from human ALS patients. Thus, RIPK1 and RIPK3 play a
critical role in mediating progressive axonal degeneration. Furthermore,
inhibiting RIPK1 kinase may provide an axonal protective strategy for the
treatment of ALS and other human degenerative diseases characterized by axonal
degeneration.
PMID- 27493190
TI - Diverse evolutionary roots and mechanistic variations of the CRISPR-Cas systems.
AB - Adaptive immunity had been long thought of as an exclusive feature of animals.
However, the discovery of the CRISPR-Cas defense system, present in almost half
of prokaryotic genomes, proves otherwise. Because of the everlasting parasite
host arms race, CRISPR-Cas has rapidly evolved through horizontal transfer of
complete loci or individual modules, resulting in extreme structural and
functional diversity. CRISPR-Cas systems are divided into two distinct classes
that each consist of three types and multiple subtypes. We discuss recent
advances in CRISPR-Cas research that reveal elaborate molecular mechanisms and
provide for a plausible scenario of CRISPR-Cas evolution. We also briefly
describe the latest developments of a wide range of CRISPR-based applications.
PMID- 27493191
TI - Epithelioid sarcoma-like hemangioendothelioma on the chest wall.
AB - Epithelioid sarcoma-like hemangioendothelioma is a rare vascular neoplasm that
usually occurs in the distal extremities of young adults. Although the overall
behavior of this neoplasm is usually indolent with a low risk of distant
metastasis, the risk of local recurrence is significant. Therefore, initial
surgical treatment with an adequate margin is important to improve the prognosis.
However, epithelioid sarcoma-like hemangioendothelioma is frequently
misdiagnosed. A preoperative misdiagnosis could result in resection without a
sufficient margin. Herein, we describe a 68-year-old man with epithelioid sarcoma
like hemangioendothelioma on the chest wall, which was treated by wide resection
despite difficulties with the preoperative diagnosis.
PMID- 27493192
TI - PcircRNA_finder: a software for circRNA prediction in plants.
AB - MOTIVATION: Recent studies reveal an important role of non-coding circular RNA
(circRNA) in the control of cellular processes. Because of differences in the
organization of plant and mammal genomes, the sensitivity and accuracy of circRNA
prediction programs using algorithms developed for animals and humans perform
poorly for plants. RESULTS: A circRNA prediction software for plants (termed
PcircRNA_finder) was developed that is more sensitive in detecting circRNAs than
other frequently used programs (such as find_circ and CIRCexplorer), Based on
analysis of simulated and real rRNA-/RNAase R RNA-Seq data from Arabidopsis
thaliana and rice PcircRNA_finder provides a more comprehensive sensitive,
precise prediction method for plants circRNAs. AVAILABILITY AND IMPLEMENTATION:
http://ibi.zju.edu.cn/bioinplant/tools/manual.htm CONTACT:
fanlj@zju.edu.cnSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27493193
TI - FARAO: the flexible all-round annotation organizer.
AB - : With decreasing costs of generating DNA sequence data, genome and metagenome
projects have become accessible to a wider scientific community. However, to
extract meaningful information and visualize the data remain challenging. We here
introduce FARAO, a highly scalable software for organization, visualization and
integration of annotation and read coverage data that can also combine output
data from several bioinformatics tools. The capabilities of FARAO can greatly aid
analyses of genomic and metagenomic datasets. AVAILABILITY AND IMPLEMENTATION:
FARAO is implemented in Perl and is supported under Unix-like operative systems,
including Linux and macOS. The Perl source code is freely available for download
under the MIT License from http://microbiology.se/software/farao/ CONTACT:
johan.bengtsson-palme@microbiology.seSupplementary information: Supplementary
data are available at Bioinformatics online.
PMID- 27493194
TI - Detection of differentially methylated regions in whole genome bisulfite
sequencing data using local Getis-Ord statistics.
AB - MOTIVATION: DNA methylation is an important epigenetic modification that has
essential role in gene regulation, cell differentiation and cancer development.
Bisulfite sequencing is a widely used technique to obtain genome-wide DNA
methylation profiles, and one of the key tasks of analyzing bisulfite sequencing
data is to detect differentially methylated regions (DMRs) among samples under
different treatment conditions. Although numerous tools have been proposed to
detect differentially methylated single CpG site (DMC) between samples, methods
for direct DMR detection, especially for complex study designs, are largely
limited. RESULTS: We present a new software, GetisDMR, for direct DMR detection.
We use beta-binomial regression to model the whole-genome bisulfite sequencing
data, where variations in methylation levels and confounding effects have been
accounted for. We employ a region-wise test statistic, which is derived from
local Getis-Ord statistics and considers the spatial correlation between nearby
CpG sites, to detect DMRs. Unlike existing methods, that attempt to infer DMRs
from DMCs based on empirical criteria, we provide statistical inference for
direct DMR detection. Through extensive simulations and an application to two
mouse datasets, we demonstrate that GetisDMR achieves better sensitivities,
positive predictive values, more exact locations and better agreement of DMRs
with current biological knowledge. AVAILABILITY AND IMPLEMENTATION: It is
available at https://github.com/DMU-lilab/GetisDMR CONTACTS: y.wen@auckland.ac.nz
or zhiguangli@dlmedu.edu.cnSupplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 27493195
TI - Novel methodology to perform sulfur hexafluoride (SF6)-based multiple-breath wash
in and washout in infants using current commercially available equipment.
AB - Multiple-breath inert gas washout (MBW) is ideally suited for early detection and
monitoring of serious lung disease, such as cystic fibrosis, in infants and young
children. Validated commercial options for the MBW technique are limited, and
suitability of nitrogen (N2)-based MBW is of concern given the detrimental effect
of exposure to pure O2 on infant breathing pattern. We propose novel methodology
using commercially available N2 MBW equipment to facilitate 4% sulfur
hexafluoride (SF6) multiple-breath inert gas wash-in and washout suitable for the
infant age range. CO2, O2, and sidestream molar mass sensor signals were used to
accurately calculate SF6 concentrations. An improved dynamic method for
synchronization of gas and respiratory flow was developed to take into account
variations in sidestream sample flow during MBW measurement. In vitro validation
of triplicate functional residual capacity (FRC) assessments was undertaken under
dry ambient conditions using lung models ranging from 90 to 267 ml, with tidal
volumes of 28-79 ml, and respiratory rates 20-60 per minute. The relative mean
(SD, 95% confidence interval) error of triplicate FRC determinations by washout
was -0.26 (1.84, -3.86 to +3.35)% and by wash-in was 0.57 (2.66, -4.66 to
+5.79)%. The standard deviations [mean (SD)] of percentage error among FRC
triplicates were 1.40 (1.14) and 1.38 (1.32) for washout and wash-in,
respectively. The novel methodology presented achieved FRC accuracy as outlined
by current MBW consensus recommendations (95% of measurements within 5%
accuracy). Further clinical evaluation is required, but this new technique, using
existing commercially available equipment, has exciting potential for research
and clinical use.
PMID- 27493196
TI - Modeling age-related changes in muscle-tendon dynamics during cyclical
contractions in the rat gastrocnemius.
AB - Efficient muscle-tendon performance during cyclical tasks is dependent on both
active and passive mechanical tissue properties. Here we examine whether age
related changes in the properties of muscle-tendon units (MTUs) compromise their
ability to do work and utilize elastic energy storage. We empirically quantified
passive and active properties of the medial gastrocnemius muscle and material
properties of the Achilles tendon in young (~6 mo) and old (~32 mo) rats. We then
used these properties in computer simulations of a Hill-type muscle model
operating in series with a Hookean spring. The modeled MTU was driven through
sinusoidal length changes and activated at a phase that optimized muscle-tendon
tuning to assess the relative contributions of active and passive elements to the
force and work in each cycle. In physiologically realistic simulations where
young and old MTUs started at similar passive forces and developed similar active
forces, the capacity of old MTUs to store elastic energy and produce positive
work was compromised. These results suggest that the observed increase in the
metabolic cost of locomotion with aging may be in part due to the recruitment of
additional muscles to compensate for the reduced work at the primary MTU.
Furthermore, the age-related increases in passive stiffness coupled with a
reduced active force capacity in the muscle can lead to shifts in the force
length and force-velocity operating range that may significantly impact
mechanical and metabolic performance. Our study emphasizes the importance of the
interplay between muscle and tendon mechanical properties in shaping MTU
performance during cyclical contractions.
PMID- 27493197
TI - No difference in exogenous carbohydrate oxidation during exercise in children
with and without impaired glucose tolerance.
AB - The capacity to match carbohydrate (CHO) utilization with availability is
impaired in insulin-resistant, obese adults at rest. Understanding exogenous
carbohydrate (CHOexo) oxidation during exercise and its association to insulin
resistance (IR) is important, especially in children at risk for type 2 diabetes.
Our objective was to examine the oxidative efficiency of CHOexo during exercise
in obese children with normal glucose tolerance (NGT) or impaired glucose
tolerance (IGT). Children attended two visits and were identified as NGT (n = 22)
or IGT (n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of
<7.8 mmol/l or >=7.8 mmol/l, respectively. Anthropometry, body composition, and
aerobic fitness (Vo2max) were assessed. Insulin and glucose at baseline, 30, 60,
90, and 120 min during the OGTT were used to calculate measures of insulin
sensitivity. On a separate day, a (13)C-enriched CHO drink was ingested before
exercise (3 * 20 min bouts) at 45% Vo2max Breath measurements were collected to
calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during
exercise was similar in IGT (17.0 +/- 3.6%) compared with NGT (17.1 +/- 4.4%) (P
= 0.90) despite lower whole body insulin sensitivity in IGT at rest (P = 0.02).
Area under the curve for insulin (AUCins) measured at rest during the OGTT was
greater in IGT compared with NGT (P = 0.04). The ability of skeletal muscle to
utilize CHOexo was not impaired during exercise in children with IGT.
PMID- 27493199
TI - Comparing Trends Between Food Insecurity and Cigarette Smoking Among Adults in
the United States, 1998 to 2011.
AB - PURPOSE: Previous studies have shown that cigarette smoking is associated with
higher rates and severity of food insecurity but do not address how population
level smoking rates change in response to changes in food security. DESIGN: Trend
analysis of serial cross-sectional data. SETTING: Data from a representative
survey of US households. PARTICIPANTS: Adults within households participating in
both the Food Security Supplement and Tobacco Use Supplement of the Current
Population Survey during 5 overlapping administrations from 1998 to 2011.
MEASURES: A "current smoker" is defined as someone who indicated that they
currently smoke on "some days" or "every day." A household's food security is
coded as "secure" or "insecure," according to responses to a food security scale,
interpreted using a US Department of Agriculture standard. ANALYSIS: Descriptive
comparison of the roughly triennial trends in the prevalence of food insecurity
and current smoking from 1998 to 2011. RESULTS: The prevalence of food insecurity
increased by 30% among adults overall versus 54% among current smokers, with most
of the changes occurring following the economic recession of 2008 and 2009. Over
this same period, the prevalence of current smoking declined by 33% among food
secure adults and only 14% among food-insecure adults. CONCLUSION: Food
insecurity increased more markedly among adult smokers than nonsmokers, and the
prevalence of smoking declined more slowly in food-insecure households,
indicating that more low-income smokers are facing hunger, which may at least
partly be due to buying cigarettes.
PMID- 27493198
TI - A single dose of histamine-receptor antagonists before downhill running alters
markers of muscle damage and delayed-onset muscle soreness.
AB - Histamine contributes to elevations in skeletal muscle blood flow following
exercise, which raises the possibility that histamine is an important mediator of
the inflammatory response to exercise. We examined the influence of
antihistamines on postexercise blood flow, inflammation, muscle damage, and
delayed-onset muscle soreness (DOMS) in a model of moderate exercise-induced
muscle damage. Subjects consumed either a combination of fexofenadine and
ranitidine (blockade, n = 12) or nothing (control, n = 12) before 45 min of
downhill running (-10% grade). Blood flow to the leg was measured before and
throughout 120 min of exercise recovery. Markers of inflammation, muscle damage,
and DOMS were obtained before and at 0, 6, 12, 24, 48, and 72 h postexercise. At
60 min postexercise, blood flow was reduced ~29% with blockade compared with
control (P < 0.05). Markers of inflammation were elevated after exercise (TNF
alpha, IL-6), but did not differ between control and blockade. Creatine kinase
concentrations peaked 12 h after exercise, and the overall response was greater
with blockade (18.3 +/- 3.2 kU.l-1.h-1) compared with control (11.6 +/- 2.0 kU.l
1.h-1; P < 0.05). Reductions in muscle strength in control (-19.3 +/- 4.3% at 24
h) were greater than blockade (-7.8 +/- 4.8%; P < 0.05) and corresponded with
greater perceptions of pain/discomfort in control compared with blockade. In
conclusion, histamine-receptor blockade reduced postexercise blood flow, had no
effect on the pattern of inflammatory markers, increased serum creatine kinase
concentrations, attenuated muscle strength loss, and reduced pain perception
following muscle-damaging exercise.NEW & NOTEWORTHY Histamine appears to be
intimately involved with skeletal muscle during and following exercise. Blocking
histamine's actions during muscle-damaging exercise, via common over-the-counter
antihistamines, resulted in increased serum creatine kinase, an indirect marker
of muscle damage. Paradoxically, blocking histamine's actions attenuated muscle
strength loss and reduced perceptions of muscle pain for 72 h following muscle
damaging exercise. These results indicate that exercise-induced histamine release
may have a broad impact on protecting muscle from exercise-induced damage.
PMID- 27493200
TI - The Relationship of Engagement in Improvement Practices to Outcome Measures in
Large-Scale Quality Improvement Initiatives.
AB - Hospital engagement networks (HENs) are part of the largest health care
improvement initiative ever undertaken. This article explores whether engagement
in improvement activities within a HEN affected quality measures. Data were drawn
from 1174 acute care hospitals. A composite quality score was created from 10
targeted topic area measures multiplied by the number of qualifying topics.
Scores improved from 5.4 (SD = 6.8) at baseline to 4.6 (5.9) at remeasurement; P
< .0001. Hospitals with higher baseline scores demonstrated greater improvement (
P < .0001) than hospitals with lower baseline scores. Hospitals with larger
Medicaid populations ( P = .023) and micropolitan ( P = .034) hospitals tended to
have greater improvement, whereas hospitals in the West ( P = .0009) did not
improve as much as hospitals in other regions. After adjusting for hospital
characteristics, hospitals with improvement champions ( P = .008), a higher level
of engagement with their state association ( P = .001), and more leadership
involvement ( P = .005) in HEN demonstrated greater improvement.
PMID- 27493201
TI - Comparative evaluation of the genomes of three common Drosophila-associated
bacteria.
AB - Drosophila melanogaster is an excellent model to explore the molecular exchanges
that occur between an animal intestine and associated microbes. Previous studies
in Drosophila uncovered a sophisticated web of host responses to intestinal
bacteria. The outcomes of these responses define critical events in the host,
such as the establishment of immune responses, access to nutrients, and the rate
of larval development. Despite our steady march towards illuminating the host
machinery that responds to bacterial presence in the gut, there are significant
gaps in our understanding of the microbial products that influence bacterial
association with a fly host. We sequenced and characterized the genomes of three
common Drosophila-associated microbes: Lactobacillus plantarum, Lactobacillus
brevis and Acetobacter pasteurianus For each species, we compared the genomes of
Drosophila-associated strains to the genomes of strains isolated from alternative
sources. We found that environmental Lactobacillus strains readily associated
with adult Drosophila and were similar to fly isolates in terms of genome
organization. In contrast, we identified a strain of A. pasteurianus that
apparently fails to associate with adult Drosophila due to an inability to grow
on fly nutrient food. Comparisons between association competent and incompetent
A. pasteurianus strains identified a short list of candidate genes that may
contribute to survival on fly medium. Many of the gene products unique to fly
associated strains have established roles in the stabilization of host-microbe
interactions. These data add to a growing body of literature that examines the
microbial perspective of host-microbe relationships.
PMID- 27493202
TI - RPGR, a prenylated retinal ciliopathy protein, is targeted to cilia in a
prenylation- and PDE6D-dependent manner.
AB - RPGR (retinitis pigmentosa GTPase regulator) is a ciliary protein associated with
several forms of inherited retinal degenerative diseases. PDE6D is a ubiquitously
expressed prenyl-binding protein and involved in ciliary targeting of prenylated
proteins. The current working model for the RPGR function depicts that RPGR acts
as a scaffold protein to recruit cargo-loaded PDE6D to primary cilia. Here, we
present evidence demonstrating an alternative relationship between RPGR and
PDE6D, in which RPGR is a cargo of PDE6D for ciliary targeting. We found that the
constitutive isoform of RPGR, which is prenylated, requires prenylation for its
ciliary localization. We also found that there are at least two independent
ciliary targeting signals in RPGR: one within the N-terminal region that contains
the RCC1-like domain and the other near the prenylation site at the C-terminus.
Ablation of PDE6D blocked ciliary targeting of RPGR. Our study indicates that
prenylated RPGR is one of the cargos of PDE6D for ciliary trafficking and
provides insight into the mechanisms by which RPGR is targeted to cilia.
PMID- 27493203
TI - Sulfur utilization of corals is enhanced by endosymbiotic algae.
AB - Sulfur-containing compounds are important components of all organisms, but few
studies have explored sulfate utilization in corals. Our previous study found
that the expression of a sulfur transporter (SLC26A11) was upregulated in the
presence of Symbiodinium cells in juveniles of the reef-building coral Acropora
tenuis In this study, we performed autoradiography using (35)S-labeled sulfate
ions ((35)SO4 (2-)) to examine the localization and amount of incorporated
radioactive sulfate in the coral tissues and symbiotic algae. Incorporated
(35)SO4 (2-) was detected in symbiotic algal cells, nematocysts, ectodermal
cells and calicoblast cells. The combined results of (35)S autoradiography and
Alcian Blue staining showed that incorporated (35)S accumulated as sulfated
glycosaminoglycans (GAGs) in the ectodermal cell layer. We also compared the
relative incorporation of (35)SO4 (2-) into coral tissues and endosymbiotic
algae, and their chemical fractions in dark versus light (photosynthetic)
conditions. The amount of sulfur compounds, such as GAGs and lipids, generated
from (35)SO4 (2-) was higher under photosynthetic conditions. Together with the
upregulation of sulfate transporters by symbiosis, our results suggest that
photosynthesis of algal endosymbionts contributes to the synthesis and
utilization of sulfur compounds in corals.
PMID- 27493204
TI - Comparison of gamma-Aminobutyric Acid, Type A (GABAA), Receptor alphabetagamma
and alphabetadelta Expression Using Flow Cytometry and Electrophysiology:
EVIDENCE FOR ALTERNATIVE SUBUNIT STOICHIOMETRIES AND ARRANGEMENTS.
AB - The subunit stoichiometry and arrangement of synaptic alphabetagamma GABAA
receptors are generally accepted as 2alpha:2beta:1gamma with a beta-alpha-gamma
beta-alpha counterclockwise configuration, respectively. Whether extrasynaptic
alphabetadelta receptors adopt the analogous beta-alpha-delta-beta-alpha subunit
configuration remains controversial. Using flow cytometry, we evaluated
expression levels of human recombinant gamma2 and delta subunits when co
transfected with alpha1 and/or beta2 subunits in HEK293T cells. Nearly identical
patterns of gamma2 and delta subunit expression were observed as follows: both
required co-transfection with alpha1 and beta2 subunits for maximal expression;
both were incorporated into receptors primarily at the expense of beta2 subunits;
and both yielded similar FRET profiles when probed for subunit adjacency,
suggesting similar underlying subunit arrangements. However, because of a slower
rate of delta subunit degradation, 10-fold less delta subunit cDNA was required
to recapitulate gamma2 subunit expression patterns and to eliminate the
functional signature of alpha1beta2 receptors. Interestingly, titrating gamma2 or
delta subunit cDNA levels progressively altered GABA-evoked currents, revealing
more than one kinetic profile for both alphabetagamma and alphabetadelta
receptors. This raised the possibility of alternative receptor isoforms, a
hypothesis confirmed using concatameric constructs for alphabetagamma receptors.
Taken together, our results suggest a limited cohort of alternative subunit
arrangements in addition to canonical beta-alpha-gamma/delta-beta-alpha
receptors, including beta-alpha-gamma/delta-alpha-alpha receptors at lower levels
of gamma2/delta expression and beta-alpha-gamma/delta-alpha-gamma/delta receptors
at higher levels of expression. These findings provide important insight into the
role of GABAA receptor subunit under- or overexpression in disease states such as
genetic epilepsies.
PMID- 27493205
TI - Structure of the Dispase Autolysis-inducing Protein from Streptomyces mobaraensis
and Glutamine Cross-linking Sites for Transglutaminase.
AB - Transglutaminase from Streptomyces mobaraensis (MTG) is an important enzyme for
cross-linking and modifying proteins. An intrinsic substrate of MTG is the
dispase autolysis-inducing protein (DAIP). The amino acid sequence of DAIP
contains 5 potential glutamines and 10 lysines for MTG-mediated cross-linking.
The aim of the study was to determine the structure and glutamine cross-linking
sites of the first physiological MTG substrate. A production procedure was
established in Escherichia coli BL21 (DE3) to obtain high yields of recombinant
DAIP. DAIP variants were prepared by replacing four of five glutamines for
asparagines in various combinations via site-directed mutagenesis. Incorporation
of biotin cadaverine revealed a preference of MTG for the DAIP glutamines in the
order of Gln-39 ? Gln-298 > Gln-345 ~ Gln-65 ? Gln-144. In the structure of DAIP
the preferred glutamines do cluster at the top of the seven-bladed beta
propeller. This suggests a targeted cross-linking of DAIP by MTG that may occur
after self-assembly in the bacterial cell wall. Based on our biochemical and
structural data of the first physiological MTG substrate, we further provide
novel insight into determinants of MTG-mediated modification, specificity, and
efficiency.
PMID- 27493206
TI - Structure of the Tuberous Sclerosis Complex 2 (TSC2) N Terminus Provides Insight
into Complex Assembly and Tuberous Sclerosis Pathogenesis.
AB - Tuberous sclerosis complex (TSC) is caused by mutations in the TSC1 and TSC2
tumor suppressor genes. The gene products hamartin and tuberin form the TSC
complex that acts as GTPase-activating protein for Rheb and negatively regulates
the mammalian target of rapamycin complex 1 (mTORC1). Tuberin contains a RapGAP
homology domain responsible for inactivation of Rheb, but functions of other
protein domains remain elusive. Here we show that the TSC2 N terminus interacts
with the TSC1 C terminus to mediate complex formation. The structure of the TSC2
N-terminal domain from Chaetomium thermophilum and a homology model of the human
tuberin N terminus are presented. We characterize the molecular requirements for
TSC1-TSC2 interactions and analyze pathological point mutations in tuberin. Many
mutations are structural and produce improperly folded protein, explaining their
effect in pathology, but we identify one point mutant that abrogates complex
formation without affecting protein structure. We provide the first structural
information on TSC2/tuberin with novel insight into the molecular function.
PMID- 27493207
TI - Metabolite-driven Regulation of Heme Uptake by the Biliverdin IXbeta/delta
Selective Heme Oxygenase (HemO) of Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa acquires extracellular heme via the Phu (Pseudomonas heme
uptake) and Has (heme assimilation system) systems. We have previously shown the
catalytic actions of heme oxygenase (HemO) along with the cytoplasmic heme
transport protein PhuS control heme flux into the cell. To further investigate
the role of the PhuS-HemO couple in modulating heme uptake, we have characterized
two HemO variants, one that is catalytically inactive (HemO H26A/K34A/K132A or
HemOin) and one that has altered regioselectivity (HemO N19K/K34A/F117Y/K132A or
HemOalpha), producing biliverdin IXalpha (BVIXalpha). HemOalpha similar to wild
type was able to interact and acquire heme from holo-PhuS. In contrast, the
HemOin variant did not interact with holo-PhuS and showed no enzymatic activity.
Complementation of a hemO deletion strain with the hemOin or hemOalpha variants
in combination with [(13)C]heme isotopic labeling experiments revealed that the
absence of BVIXbeta and BVIXdelta leads to a decrease in extracellular levels of
hemophore HasA. We propose BVIXbeta and/or BVIXdelta transcriptionally or post
transcriptionally regulates HasA. Thus, coupling the PhuS-dependent flux of heme
through HemO to feedback regulation of the cell surface signaling system through
HasA allows P. aeruginosa to rapidly respond to fluctuating extracellular heme
levels independent of the iron status of the cell.
PMID- 27493209
TI - Carbon-Fixing Reactions of Photosynthesis.
AB - plantcell;28/7/tpc.116.tt0716/FIG1F1fig1Photosynthesis in plants converts the
energy of sunlight into chemical energy. Although photosynthesis involves many
proteins and catalytic processes, it often is described as two sets of reactions,
the light-dependent reactions and the carbon-fixing reactions. This lesson
introduces the core biochemistry of the carbon-fixing reactions of
photosynthesis, as well as its variations, C4 and CAM. Finally, it addresses how
and why plants are affected by rising atmospheric CO2 levels, and research
efforts to increase photosynthetic efficiency in current and future conditions.
PMID- 27493208
TI - Identification of Two Conserved Residues Involved in Copper Release from
Chloroplast PIB-1-ATPases.
AB - Copper is an essential transition metal for living organisms. In the plant model
Arabidopsis thaliana, half of the copper content is localized in the chloroplast,
and as a cofactor of plastocyanin, copper is essential for photosynthesis. Within
the chloroplast, copper delivery to plastocyanin involves two transporters of the
PIB-1-ATPases subfamily: HMA6 at the chloroplast envelope and HMA8 in the
thylakoid membranes. Both proteins are high affinity copper transporters but
share distinct enzymatic properties. In the present work, the comparison of 140
sequences of PIB-1-ATPases revealed a conserved region unusually rich in
histidine and cysteine residues in the TMA-L1 region of eukaryotic chloroplast
copper ATPases. To evaluate the role of these residues, we mutated them in HMA6
and HMA8. Mutants of interest were selected from phenotypic tests in yeast and
produced in Lactococcus lactis for further biochemical characterizations using
phosphorylation assays from ATP and Pi Combining functional and structural data,
we highlight the importance of the cysteine and the first histidine of the
CX3HX2H motif in the process of copper release from HMA6 and HMA8 and propose a
copper pathway through the membrane domain of these transporters. Finally, our
work suggests a more general role of the histidine residue in the transport of
copper by PIB-1-ATPases.
PMID- 27493210
TI - Characterization of paramyosin and thin filaments in the smooth muscle of acorn
worm, a member of hemichordates.
AB - Paramyosin is a myosin-binding protein characteristic of invertebrate animals,
while troponin is a Ca2+-dependent regulator of muscle contraction. Both proteins
are widely distributed in protostomes, while in deuterostomes, their distribution
is limited; namely, presence of paramyosin and absence of troponin are common
features in echinoderm muscles, while muscles of chordates contain troponin but
lack paramyosin. In this study, we examined the muscle of a hemichordate, acorn
worm, to clarify whether this animal is like echinoderms or like the other
deuterostome animals. We found a 100-kDa protein in the smooth muscle of acorn
worm. This protein was identified with paramyosin, since the purified protein
formed paracrystals with a constant axial periodicity in the presence of divalent
cations as paramyosin of other animals, showed ability to interact with myosin
and shared common antigenicity with echinoderm paramyosin. On the other hand,
troponin band was not detected in isolated thin filaments, and the filaments
increased myosin-ATPase activity in a Ca2+-independent manner. The results
indicate that troponin is lacking in thin filaments of acorn worm muscle just as
in those of echinoderms. The muscle of hemichordate acorn worm is quite similar
to echinoderm muscles, but different from chordate muscles.
PMID- 27493211
TI - Structure and function of [NiFe] hydrogenases.
AB - Hydrogenases catalyze the reversible conversion of molecular hydrogen to protons
and electrons via a heterolytic splitting mechanism. The active sites of [NiFe]
hydrogenases comprise a dinuclear Ni-Fe center carrying CO and CN- ligands. The
catalytic activity of the standard (O2-sensitive) [NiFe] hydrogenases vanishes
under aerobic conditions. The O2-tolerant [NiFe] hydrogenases can sustain H2
oxidation activity under atmospheric conditions. These hydrogenases have very
similar active site structures that change the ligand sphere during the
activation/catalytic process. An important structural difference between these
hydrogenases has been found for the proximal iron-sulphur cluster located in the
vicinity of the active site. This unprecedented [4Fe-3S]-6Cys cluster can supply
two electrons, which lead to rapid recovery of the O2 inactivation, to the [NiFe]
active site.
PMID- 27493212
TI - Shedding Light on Endometriosis.
PMID- 27493213
TI - The Heat Stress Factor HSFA6b Connects ABA Signaling and ABA-Mediated Heat
Responses.
AB - Heat stress response (HSR) is a conserved mechanism developed to increase the
expression of heat shock proteins (HSPs) via a heat shock factor (HSF)-dependent
mechanism. Signaling by the stress phytohormone abscisic acid (ABA) is involved
in acquired thermotolerance as well. Analysis of Arabidopsis (Arabidopsis
thaliana) microarray databases revealed that the expression of HSFA6b, a class A
HSF, extensively increased with salinity, osmotic, and cold stresses, but not
heat. Here, we show that HSFA6b plays a pivotal role in the response to ABA and
in thermotolerance. Salt-inducible HSFA6b expression was down-regulated in ABA
insensitive and -deficient mutants; however, exogenous ABA application restored
expression in ABA-deficient, but not -insensitive plants. Thus, ABA signaling is
required for proper HSFA6b expression. A transcriptional activation assay of
protoplasts revealed that ABA treatment and coexpression of an ABA signaling
master effector, ABA-RESPONSIVE ELEMENT-BINDING PROTEIN1, could activate the
HSFA6b promoter. In addition, HSFA6b directly bound to the promoter of
DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN2A and enhanced its expression.
Analysis of ABA responses in seed germination, cotyledon greening, and root
growth as well as salt and drought tolerance in HSFA6b-null, overexpression, and
dominant negative mutants revealed that HSFA6b is a positive regulator
participating in ABA-mediated salt and drought resistance. Thermoprotection tests
showed that HSFA6b was required for thermotolerance acquisition. Our study
reveals a network in which HSFA6b operates as a downstream regulator of the ABA
mediated stress response and is required for heat stress resistance. This new ABA
signaling pathway is integrated into the complex HSR network in planta.
PMID- 27493214
TI - Histidine Regulates Seed Oil Deposition through Abscisic Acid Biosynthesis and
beta-Oxidation.
AB - The storage compounds are deposited into plant seeds during maturation. As the
model oilseed species, Arabidopsis (Arabidopsis thaliana) has long been studied
for seed oil deposition. However, the regulation of this process remains unclear.
Through genetic screen with a seed oil body-specific reporter, we isolated low
oil1 (loo1) mutant. LOO1 was mapped to HISTIDINE BIOSYNTHESIS NUMBER 1A (HISN1A).
HISN1A catalyzes the first step of His biosynthesis. Oil significantly decreased,
and conversely proteins markedly increased in hisn1a mutants, indicating that
HISN1A regulates both oil accumulation and the oil-protein balance. HISN1A was
predominantly expressed in embryos and root tips. Accordingly, the hisn1a mutants
exhibited developmental phenotype especially of seeds and roots. Transcriptional
profiling displayed that beta-oxidation was the major metabolic pathway
downstream of HISN1A beta-Oxidation was induced in hisn1a mutants, whereas it was
reduced in 35S:HISN1A-transgenic plants. In plants, seed storage oil is broken
down by beta-oxidation, which is controlled by abscisic acid (ABA). We found that
His activated genes of ABA biosynthesis and correspondingly advanced ABA
accumulation. Exogenous ABA rescued the defects of hisn1a mutants, whereas
mutation of ABA DEFICIENT2, a key enzyme in ABA biosynthesis, blocked the effect
of His on beta-oxidation, indicating that ABA mediates His regulation in beta
oxidation. Intriguingly, structural analysis showed that a potential His-binding
domain was present in the general amino acid sensors GENERAL CONTROL NON
DEREPRESSIBLE2 and PII, suggesting that His may serve as a signal molecule. Taken
together, our study reveals that His promotes plant seed oil deposition through
ABA biosynthesis and beta-oxidation.
PMID- 27493216
TI - Carbohydrate-binding domain of the POMGnT1 stem region modulates O-mannosylation
sites of alpha-dystroglycan.
AB - The dystrophin glycoprotein complex, which connects the cell membrane to the
basement membrane, is essential for a variety of biological events, including
maintenance of muscle integrity. An O-mannose-type GalNAc-beta1,3-GlcNAc-beta1,4
(phosphate-6)-Man structure of alpha-dystroglycan (alpha-DG), a subunit of the
complex that is anchored to the cell membrane, interacts directly with laminin in
the basement membrane. Reduced glycosylation of alpha-DG is linked to some types
of inherited muscular dystrophy; consistent with this relationship, many disease
related mutations have been detected in genes involved in O-mannosyl glycan
synthesis. Defects in protein O-linked mannose beta1,2-N
acetylglucosaminyltransferase 1 (POMGnT1), a glycosyltransferase that
participates in the formation of GlcNAc-beta1,2-Man glycan, are causally related
to muscle-eye-brain disease (MEB), a congenital muscular dystrophy, although the
role of POMGnT1 in postphosphoryl modification of GalNAc-beta1,3-GlcNAc-beta1,4
(phosphate-6)-Man glycan remains elusive. Our crystal structures of POMGnT1
agreed with our previous results showing that the catalytic domain recognizes
substrate O-mannosylated proteins via hydrophobic interactions with little
sequence specificity. Unexpectedly, we found that the stem domain recognizes the
beta-linked GlcNAc of O-mannosyl glycan, an enzymatic product of POMGnT1. This
interaction may recruit POMGnT1 to a specific site of alpha-DG to promote GlcNAc
beta1,2-Man clustering and also may recruit other enzymes that interact with
POMGnT1, e.g., fukutin, which is required for further modification of the GalNAc
beta1,3-GlcNAc-beta1,4-(phosphate-6)-Man glycan. On the basis of our findings, we
propose a mechanism for the deficiency in postphosphoryl modification of the
glycan observed in POMGnT1-KO mice and MEB patients.
PMID- 27493215
TI - Near-atomic cryo-EM structure of PRC1 bound to the microtubule.
AB - Proteins that associate with microtubules (MTs) are crucial to generate MT arrays
and establish different cellular architectures. One example is PRC1 (protein
regulator of cytokinesis 1), which cross-links antiparallel MTs and is essential
for the completion of mitosis and cytokinesis. Here we describe a 4-A-resolution
cryo-EM structure of monomeric PRC1 bound to MTs. Residues in the spectrin domain
of PRC1 contacting the MT are highly conserved and interact with the same pocket
recognized by kinesin. We additionally found that PRC1 promotes MT assembly even
in the presence of the MT stabilizer taxol. Interestingly, the angle of the
spectrin domain on the MT surface corresponds to the previously observed cross
bridge angle between MTs cross-linked by full-length, dimeric PRC1. This finding,
together with molecular dynamic simulations describing the intrinsic flexibility
of PRC1, suggests that the MT-spectrin domain interface determines the geometry
of the MT arrays cross-linked by PRC1.
PMID- 27493217
TI - Gram-negative trimeric porins have specific LPS binding sites that are essential
for porin biogenesis.
AB - The outer membrane (OM) of gram-negative bacteria is an unusual asymmetric
bilayer with an external monolayer of lipopolysaccharide (LPS) and an inner layer
of phospholipids. The LPS layer is rigid and stabilized by divalent cation cross
links between phosphate groups on the core oligosaccharide regions. This means
that the OM is robust and highly impermeable to toxins and antibiotics. During
their biogenesis, OM proteins (OMPs), which function as transporters and
receptors, must integrate into this ordered monolayer while preserving its
impermeability. Here we reveal the specific interactions between the trimeric
porins of Enterobacteriaceae and LPS. Isolated porins form complexes with
variable numbers of LPS molecules, which are stabilized by calcium ions. In
earlier studies, two high-affinity sites were predicted to contain groups of
positively charged side chains. Mutation of these residues led to the loss of LPS
binding and, in one site, also prevented trimerization of the porin, explaining
the previously observed effect of LPS mutants on porin folding. The high
resolution X-ray crystal structure of a trimeric porin-LPS complex not only helps
to explain the mutagenesis results but also reveals more complex, subtle porin
LPS interactions and a bridging calcium ion.
PMID- 27493219
TI - From fire whirls to blue whirls and combustion with reduced pollution.
AB - Fire whirls are powerful, spinning disasters for people and surroundings when
they occur in large urban and wildland fires. Whereas fire whirls have been
studied for fire-safety applications, previous research has yet to harness their
potential burning efficiency for enhanced combustion. This article presents
laboratory studies of fire whirls initiated as pool fires, but where the fuel
sits on a water surface, suggesting the idea of exploiting the high efficiency of
fire whirls for oil-spill remediation. We show the transition from a pool fire,
to a fire whirl, and then to a previously unobserved state, a "blue whirl." A
blue whirl is smaller, very stable, and burns completely blue as a hydrocarbon
flame, indicating soot-free burning. The combination of fast mixing, intense
swirl, and the water-surface boundary creates the conditions leading to nearly
soot-free combustion. With the worldwide need to reduce emissions from both
wanted and unwanted combustion, discovery of this state points to possible new
pathways for reduced-emission combustion and fuel-spill cleanup. Because current
methods to generate a stable vortex are difficult, we also propose that the blue
whirl may serve as a research platform for fundamental studies of vortices and
vortex breakdown in fluid mechanics.
PMID- 27493218
TI - Alternative haplotypes of antigen processing genes in zebrafish diverged early in
vertebrate evolution.
AB - Antigen processing and presentation genes found within the MHC are among the most
highly polymorphic genes of vertebrate genomes, providing populations with
diverse immune responses to a wide array of pathogens. Here, we describe
transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering
the most extensive diversity within the antigen processing and presentation genes
of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic
context within a remarkably divergent haplotype of the core MHC region on
chromosome 19 for six expressed genes not found in the zebrafish reference
genome: mhc1uga, proteasome-beta 9b (psmb9b), psmb8f, and previously unknown
genes psmb13b, tap2d, and tap2e We identify ancient lineages for Psmb13 within a
proteasome branch previously thought to be monomorphic and provide evidence of
substantial lineage diversity within each of three major trifurcations of
catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11,
Psmb6/Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13. Strikingly, nearby tap2 and MHC
class I genes also retain ancient sequence lineages, indicating that alternative
lineages may have been preserved throughout the entire MHC pathway since early
diversification of the adaptive immune system ~500 Mya. Furthermore,
polymorphisms within the three MHC pathway steps (antigen cleavage, transport,
and presentation) are each predicted to alter peptide specificity. Lastly,
comparative analysis shows that antigen processing gene diversity is far more
extensive than previously realized (with ancient coelacanth psmb8 lineages, shark
psmb13, and tap2t and psmb10 outside the teleost MHC), implying distinct immune
functions and conserved roles in shaping MHC pathway evolution throughout
vertebrates.
PMID- 27493221
TI - Waltzing route toward double-helix formation in cholesteric shells.
AB - Liquid crystals, when confined to a spherical shell, offer fascinating
possibilities for producing artificial mesoscopic atoms, which could then self
assemble into materials structured at a nanoscale, such as photonic crystals or
metamaterials. The spherical curvature of the shell imposes topological
constraints in the molecular ordering of the liquid crystal, resulting in the
formation of defects. Controlling the number of defects, that is, the shell
valency, and their positions, is a key success factor for the realization of
those materials. Liquid crystals with helical cholesteric order offer a
promising, yet unexplored way of controlling the shell defect configuration. In
this paper, we study cholesteric shells with monovalent and bivalent defect
configurations. By bringing together experiments and numerical simulations, we
show that the defects appearing in these two configurations have a complex inner
structure, as recently reported for simulated droplets. Bivalent shells possess
two highly structured defects, which are composed of a number of smaller defect
rings that pile up through the shell. Monovalent shells have a single radial
defect, which is composed of two nonsingular defect lines that wind around each
other in a double-helix structure. The stability of the bivalent configuration
against the monovalent one is controlled by c = h/p, where h is the shell
thickness and p the cholesteric helical pitch. By playing with the shell
geometry, we can trigger the transition between the two configurations. This
transition involves a fascinating waltz dynamics, where the two defects come
closer while turning around each other.
PMID- 27493220
TI - Crystal structure of a human neuronal nAChR extracellular domain in pentameric
assembly: Ligand-bound alpha2 homopentamer.
AB - In this study we report the X-ray crystal structure of the extracellular domain
(ECD) of the human neuronal alpha2 nicotinic acetylcholine receptor (nAChR)
subunit in complex with the agonist epibatidine at 3.2 A. Interestingly, alpha2
was crystallized as a pentamer, revealing the intersubunit interactions in a wild
type neuronal nAChR ECD and the full ligand binding pocket conferred by two
adjacent alpha subunits. The pentameric assembly presents the conserved
structural scaffold observed in homologous proteins, as well as distinctive
features, providing unique structural information of the binding site between
principal and complementary faces. Structure-guided mutagenesis and
electrophysiological data confirmed the presence of the alpha2(+)/alpha2(-)
binding site on the heteromeric low sensitivity alpha2beta2 nAChR and validated
the functional importance of specific residues in alpha2 and beta2 nAChR
subunits. Given the pathological importance of the alpha2 nAChR subunit and the
high sequence identity with alpha4 (78%) and other neuronal nAChR subunits, our
findings offer valuable information for modeling several nAChRs and ultimately
for structure-based design of subtype specific drugs against the nAChR associated
diseases.
PMID- 27493223
TI - Human serine racemase is allosterically modulated by NADH and reduced
nicotinamide derivatives.
AB - Serine racemase catalyzes both the synthesis and the degradation of d-serine, an
obligatory co-agonist of the glutamatergic NMDA receptors. It is allosterically
controlled by adenosine triphosphate (ATP), which increases its activity around 7
fold through a co-operative binding mechanism. Serine racemase has been proposed
as a drug target for the treatment of several neuropathologies but, so far, the
search has been directed only toward the active site, with the identification of
a few, low-affinity inhibitors. Following the recent observation that
nicotinamide adenine dinucleotide (reduced form) (NADH) inhibits serine racemase,
here we show that the inhibition is partial, with an IC50 of 246 +/- 63 MUM,
several-fold higher than NADH intracellular concentrations. At saturating
concentrations of NADH, ATP binds with a 2-fold lower affinity and without co
operativity, suggesting ligand competition. NADH also reduces the weak activity
of human serine racemase in the absence of ATP, indicating an additional ATP
independent inhibition mechanism. By dissecting the NADH molecule, we discovered
that the inhibitory determinant is the N-substituted 1,4-dihydronicotinamide
ring. Particularly, the NADH precursor 1,4-dihydronicotinamide mononucleotide
exhibited a partial mixed-type inhibition, with a KI of 18 +/- 7 MUM. Docking
simulations suggested that all 1,4-dihydronicotinamide derivatives bind at the
interdimeric interface, with the ring positioned in an unoccupied site next to
the ATP-binding site. This newly recognized allosteric site might be exploited
for the design of high-affinity serine racemase effectors to finely modulate d
serine homeostasis.
PMID- 27493224
TI - Bridging the genotype-phenotype gap in 3D.
PMID- 27493222
TI - Kinetic and thermodynamic framework for P4-P6 RNA reveals tertiary motif
modularity and modulation of the folding preferred pathway.
AB - The past decade has seen a wealth of 3D structural information about complex
structured RNAs and identification of functional intermediates. Nevertheless,
developing a complete and predictive understanding of the folding and function of
these RNAs in biology will require connection of individual rate and equilibrium
constants to structural changes that occur in individual folding steps and
further relating these steps to the properties and behavior of isolated,
simplified systems. To accomplish these goals we used the considerable structural
knowledge of the folded, unfolded, and intermediate states of P4-P6 RNA. We
enumerated structural states and possible folding transitions and determined rate
and equilibrium constants for the transitions between these states using single
molecule FRET with a series of mutant P4-P6 variants. Comparisons with simplified
constructs containing an isolated tertiary contact suggest that a given tertiary
interaction has a stereotyped rate for breaking that may help identify structural
transitions within complex RNAs and simplify the prediction of folding kinetics
and thermodynamics for structured RNAs from their parts. The preferred folding
pathway involves initial formation of the proximal tertiary contact. However,
this preference was only ~10 fold and could be reversed by a single point
mutation, indicating that a model akin to a protein-folding contact order model
will not suffice to describe RNA folding. Instead, our results suggest a strong
analogy with a modified RNA diffusion-collision model in which tertiary elements
within preformed secondary structures collide, with the success of these
collisions dependent on whether the tertiary elements are in their rare binding
competent conformations.
PMID- 27493225
TI - Untapping root system architecture for crop improvement.
PMID- 27493227
TI - Compulsive reading: Stars with addictions, to Star Wars.
PMID- 27493228
TI - Psychiatric classification: Merely repetitive and problematic?
PMID- 27493229
TI - Movies in Mind: Star Wars The consciousness 'awakens'.
PMID- 27493226
TI - Dual transcriptome analysis reveals insights into the response to Rice black
streaked dwarf virus in maize.
AB - Maize rough dwarf disease (MRDD) is a viral infection that results in heavy yield
losses in maize worldwide, particularly in the summer maize-growing regions of
China. MRDD is caused by the Rice black-streaked dwarf virus (RBSDV). In the
present study, analyses of microRNAs (miRNAs), the degradome, and transcriptome
sequences were used to elucidate the RBSDV-responsive pathway(s) in maize.
Genomic analysis indicated that the expression of three non-conserved and 28
conserved miRNAs, representing 17 known miRNA families and 14 novel miRNAs, were
significantly altered in response to RBSDV when maize was inoculated at the V3
(third leaf) stage. A total of 99 target transcripts from 48 genes of 10 known
miRNAs were found to be responsive to RBSDV infection. The annotations of these
target genes include a SQUAMOSA promoter binding (SPB) protein, a P450 reductase,
an oxidoreductase, and a ubiquitin-related gene, among others. Characterization
of the entire transcriptome suggested that a total of 28 and 1085 differentially
expressed genes (DEGs) were detected at 1.5 and 3.0 d, respectively, after
artificial inoculation with RBSDV. The expression patterns of cell wall- and
chloroplast-related genes, and disease resistance- and stress-related genes
changed significantly in response to RBSDV infection. The negatively regulated
genes GRMZM2G069316 and GRMZM2G031169, which are the target genes for miR169i-p5
and miR8155, were identified as a nucleolin and a NAD(P)-binding Rossmann-fold
superfamily protein in maize, respectively. The gene ontology term GO:0003824,
including GRMZM2G031169 and other 51 DEGs, was designated as responsive to RBSDV.
PMID- 27493230
TI - An erudite encounter with: Jules Angst.
PMID- 27493231
TI - Restoration of microRNA-212 causes a G0/G1 cell cycle arrest and apoptosis in
adult T-cell leukemia/lymphoma cells by repressing CCND3 expression.
AB - Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive T-cell malignancy.
This study was designed to explore the expression and functional significance of
microRNA (miR)-212 in ATL. The expression of miR-212 in human ATL tissues and
cell lines were investigated. Gain-of-function experiments were carried out to
determine the roles of miR-212 in cell proliferation, tumorigenesis, cell cycle
progression, and apoptosis. We also identified and functionally characterized the
target genes of miR-212 in ATL cells. Compared with normal lymph node biopsies,
lymphoma samples from ATL patients displayed underexpression of miR-212
(p=0.0032). Consistently, miR-212 was downregulated in human ATL cell lines,
compared with normal T lymphocytes. Restoration of miR-212 significantly (p<0.05)
inhibited ATL cell proliferation and tumorigenesis in mice. Overexpression of miR
212 led to an accumulation of G0/G1-phase cells and a concomitant reduction of S
phase cells. Moreover, enforced expression of miR-212-induced significant
apoptosis in ATL cells. CCND3, which encodes a cell cycle regulator cyclin D3,
was identified as a direct target of miR-212 in ATL cells. Rescue experiments
with a miR-212-resistant variant of CCND3 demonstrated that overexpression of
CCND3 restored cell-cycle progression and attenuated apoptotic response in miR
212-overexpressing ATL cells. Taken together, miR-212 exerts growth-suppressive
effects in ATL cells largely by targeting CCND3 and may have therapeutic
potential in ATL.
PMID- 27493232
TI - Theory of mind predicts severity level in autism.
AB - We investigated whether theory of mind skills can indicate autism spectrum
disorder severity. In all, 62 children with autism spectrum disorder completed a
developmentally sensitive theory of mind battery. We used intelligence quotient,
Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnosis and
level of support needed as indicators of severity level. Using hierarchical
cluster analysis, we found three distinct clusters of theory of mind ability:
early-developing theory of mind (Cluster 1), false-belief reasoning (Cluster 2)
and sophisticated theory of mind understanding (Cluster 3). The clusters
corresponded to severe, moderate and mild autism spectrum disorder. As an
indicator of level of support needed, cluster grouping predicted the type of
school children attended. All Cluster 1 children attended autism-specific
schools; Cluster 2 was divided between autism-specific and special needs schools
and nearly all Cluster 3 children attended general special needs and mainstream
schools. Assessing theory of mind skills can reliably discriminate severity
levels within autism spectrum disorder.
PMID- 27493233
TI - Experiences of posttraumatic growth in siblings of children with cancer.
AB - As survival rates continue to improve for children diagnosed with cancer, strides
in achieving better psychosocial outcomes for both children with cancer and their
families have been accentuated. The current study aimed to explore the
experiences of siblings of children diagnosed with cancer and attempted to
overcome some of the limitations described in previous research. Primarily, the
study considered the theoretical framework of posttraumatic growth (PTG) in the
project design and analysis. Semi-structured interviews were completed with six
siblings. Thematic analysis was employed to identify themes within the data set
as a whole. The data revealed that siblings experienced a range of difficult
emotions throughout the cancer trajectory as well as experiencing remarkable
changes in their lives. This included both positive and negative changes. These
changes included increased empathy and resilience, improved family relationships,
disrupted routine, increased responsibility and perceived changes in the ill
child. Siblings described factors which they found helpful and unhelpful in
adjusting to these changes. The report ends with a discussion of the themes and
their clinical and theoretical implications. The report also highlights the
research limitations and areas for future investigation.
PMID- 27493234
TI - Cranial dural permeability of inflammatory nociceptive mediators: Potential
implications for animal models of migraine.
AB - Background Application of inflammatory mediators to the cranial dura has been
used as a method to activate and sensitize neurons in the meningeal sensory
pathway in preclinical behavioral studies of headache mechanisms. However, the
relatively high concentrations and volumes used in these studies raise the
question of whether the applied agents might pass through the dura to act
directly on central neurons, thus bypassing the dural afferent pathway. Methods
We used a radiolabeling approach to quantify the meningeal permeability of two of
the inflammatory mediators, 5-HT and PGE2, when applied to the cranial dura as
part of an inflammatory mixture used in preclinical headache models. Results Both
agents could be detected in samples taken four hours after dural application in
the cerebrospinal fluid (CSF) and, in measurements made only for PGE2, in the
central nervous system (CNS) as well. Based on our measurements, we made
estimates of the CSF and CNS levels that would be attained with the higher
concentrations and volumes of 5HT and PGE2 that were exogenously applied in
previous pre-clinical headache studies. These estimated levels were comparable to
or larger than normal endogenous levels, potentially large enough to have
physiological effects. Conclusions The finding that the cranial meninges are
permeable to the two tested inflammatory mediators PGE2 and 5-HT raises some
uncertainty about whether the behavioral changes observed in prior pre-clinical
headache studies with these as well as other agents can be attributed entirely to
the activation of dural nociceptors, particularly when the agents are applied at
concentrations several orders of magnitude above physiological levels.
PMID- 27493235
TI - Reply to Chen et al.
PMID- 27493236
TI - Heteroresistance of Mycobacterium tuberculosis Strains May Be Associated More
Strongly With Poor Treatment Outcomes Than Within-Host Heterogeneity of M.
tuberculosis Infection.
PMID- 27493237
TI - Antibodies and Acidic Environment Do Not Enhance HIV-1 Transcytosis.
AB - A limited number of human immunodeficiency virus type 1 (HIV-1) variants
initially infect HIV-1-naive individuals. Recent studies imply that this may
occur because generally inefficient transcytosis across intact mucosal surfaces
could be enhanced for specific viruses with bound antibodies and in the presence
of acidic pH. We found that transcytosis of both cell-free and cell-associated
viruses with diverse envelopes was significantly decreased in the presence of
either antibodies or plasma from chronically infected transmitting partners
regardless of pH. Transmitted variants also did not have greater transmigration
as compared to chronic-infection strains. Enhanced translocation capacity is
unlikely to influence which HIV-1 variant establishes infection.
PMID- 27493238
TI - Preexisting Antibody-Dependent Cellular Cytotoxicity-Activating Antibody
Responses Are Stable Longitudinally and Cross-reactive Responses Are Not Boosted
by Recent Influenza Exposure.
AB - Cross-reactive influenza virus-specific antibody-dependent cellular cytotoxicity
(ADCC)-activating antibodies are readily detected in healthy adults. However,
little is known about the kinetics of these ADCC responses. We used retrospective
serial blood samples from healthy donors to investigate this topic. All donors
had ADCC responses against 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09)
and avian influenza A(H7N9) virus hemagglutinins (HAs) despite being seronegative
for these viruses in standard hemagglutination inhibition and microneutralization
serological assays. A(H1N1)pdm09 exposure did not boost ADCC responses specific
for H7 HA antigens. H7 HA ADCC responses were variable longitudinally within
donors, suggesting that these cross-reactive antibodies are unstable. We found no
correlation between ADCC responses to the H7 HA and either influenza virus
specific immunoglobulin G1 concentration or age.
PMID- 27493240
TI - Rearing Larvae of the Avian Nest Parasite, Philornis downsi (Diptera: Muscidae),
on Chicken Blood-Based Diets.
AB - Captive rearing of insect pests is necessary to understand their biology and to
develop control methods. The avian nest fly, Philornis downsi Dodge and Aitken,
is a blood-sucking parasite during its larval stage and a serious threat to
endemic birds in the Galapagos Islands where it is considered invasive. In order
to procure large numbers of flies for biological studies, rearing media and diets
were trialed for rearing the larval stage of P. downsi under controlled
conditions in the absence of its avian host. P. downsi eggs were obtained from
field-caught female flies, and once eggs hatched they were reared on chicken
blood for the first 3 d. Following this, three diets were tested on second- and
third-instar larvae: 1) chicken blood only; 2) chicken blood, hydrolyzed protein
and dried milk powder; and 3) chicken blood, hydrolyzed protein and brewer's
yeast. Out of 385 P. downsi larvae tested, we were able to rear 50 larvae to the
adult stage. The highest level of mortality was found in the first-instar larvae.
Survivorship of second- and third-instar larvae was similar irrespective of diet
and diet did not significantly influence larval or pupal development times;
though larvae fed the diet with brewer's yeast developed marginally faster. Pupal
weights were similar to those of larvae that had developed on bird hosts in the
field. To our knowledge, this is the first effective protocol for rearing a
hematophagous parasitic avian fly from egg to adult in the absence of a living
host.
PMID- 27493239
TI - An Adenovirus Vaccine Expressing Ebola Virus Variant Makona Glycoprotein Is
Efficacious in Guinea Pigs and Nonhuman Primates.
AB - A licensed vaccine against Ebola virus (EBOV) remains unavailable, despite >11
000 deaths from the 2014-2016 outbreak of EBOV disease in West Africa. Past
studies have shown that recombinant vaccine viruses expressing EBOV glycoprotein
(GP) are able to protect nonhuman primates (NHPs) from a lethal EBOV challenge.
However, these vaccines express the viral GP-based EBOV variants found in Central
Africa, which has 97.3% amino acid homology to the Makona variant found in West
Africa. Our previous study showed that a recombinant adenovirus serotype 5 (Ad5)
vectored vaccine expressing the Makona EBOV GP (MakGP) was safe and immunogenic
during clinical trials in China, but it is unknown whether the vaccine protects
against EBOV infection. Here, we demonstrate that guinea pigs immunized with Ad5
MakGP developed robust humoral responses and were protected against exposure to
guinea pig-adapted EBOV. Ad5-MakGP also elicited specific B- and T-cell immunity
in NHPs and conferred 100% protection when animals were challenged 4 weeks after
immunization. These results support further clinical development of this
candidate and highlight the utility of Ad5-MakGP as a prophylactic measure in
future outbreaks of EBOV disease.
PMID- 27493241
TI - M2-polarized and tumor-associated macrophages alter NK cell phenotype and
function in a contact-dependent manner.
AB - The crosstalk between NK cells and M1 macrophages has a vital role in the
protection against infections and tumor development. However, macrophages in the
tumor resemble an M2 phenotype, and, at present, their effect on NK cells is less
clear. This study investigated whether tumor-associated macrophages (TAMs) have a
role in altering NK cell function and phenotype using in vitro cocultures of
murine NK cells with peritoneal or bone marrow-derived, M2-polarized macrophages
or TAMs isolated from spontaneous mouse breast tumors. We report here that both
peritoneal and bone marrow-derived M2 macrophages, as well as TAMs, substantially
inhibit NK cell activation and concordant cytotoxicity against tumor cells. The
mechanism for this inhibition was found to require contact between the respective
cell types. Both M2 macrophages and TAMs are producers of the immunosuppressive
cytokine TGF-beta. The inhibition of TGF-beta restored the cytotoxicity of NK
cells in contact with M2 macrophages, implicating TGF-beta in the mechanism for
NK cell inhibition. In addition to affecting NK cell function, TAMs also induced
a CD27lowCD11bhigh-exhausted NK cell phenotype, which corresponds with the
reduced activation and cytotoxicity observed. This study reveals a novel
implication of TAMs in the tumor-associated inhibition of NK cell function by
demonstrating their capacity to directly alter NK cell cytotoxicity and phenotype
in a contact-dependent mechanism involving TGF-beta. These findings identify the
interaction between NK cells and TAMs as a prospective therapeutic target to
enhance NK cell effector function for effective NK cell cancer therapies.
PMID- 27493242
TI - TLR2-mediated leukocyte trafficking to the developing brain.
AB - Inflammation is a significant risk factor for brain injury in the perinatal
period. In this study, we tested the hypothesis that activation of peripheral TLR
induces inflammation in the brain, including leukocyte trafficking. Postnatal day
8 mice were injected intraperitoneally with a TLR1/2 (Pam3CSK4, P3C), TLR2/6 (FSL
1) or TLR4 (LPS) agonist, and the peripheral and central cytokine and chemokine
response was determined. Infiltration of immune cells to the CSF and brain was
examined by flow cytometry, and brain permeability was investigated by
radioactively labeled sucrose. We report that peripheral administration of P3C to
neonatal mice induces significant influx of leukocytes, mainly neutrophils and
monocytes, to the CSF and brain. Infiltration of leukocytes was TLR2 and MyD88
dependent, but largely absent after administration of LPS or FSL-1. PC3-mediated
accumulation of immune cells in the brain was observed in classic CNS-leukocyte
gateways, the subarachnoid space and choroid plexus, as well as in the median
eminence. Although P3C and LPS induced a similar degree of peripheral
inflammatory responses, P3C provoked a distinct brain chemokine response and
increased permeability, in particular, of the blood-CSF barrier. Collectively,
our results do not support the hypothesis that TLR activation, in general,
induces immune cell infiltration to the brain. Instead, we have discovered a
specific TLR2-mediated mechanism of CNS inflammation and leukocyte invasion into
the neonatal brain. This interaction between peripheral and central immune
responses is to a large extent via the blood-CSF barrier.
PMID- 27493244
TI - Murine liver-resident group 1 innate lymphoid cells regulate optimal priming of
anti-viral CD8+ T cells.
AB - The liver contains 2 transcriptionally distinct group 1 ILC subsets: CD49a+ ILC1s
and CD49b+ NK cells. However, little is known about how group 1 ILCs contribute
to hepatic immune responses. Therefore, we characterized murine liver-resident
group 1 ILCs and found that CD49a+ ILC1s express high levels of the inhibitory
receptor NKG2A and localize near DCs in perivascular spaces surrounding the
portal triads. Upon hepatic viral infection, NKG2A signaling in group 1 ILCs,
especially in CD49a+ ILC1s, inhibits CXCL9 expression required for robust
accumulation of IFN-gamma+CD49b+ NK cells. As a consequence, NKG2A-/- mice showed
increased numbers of IFN-gamma-producing NK cells that preferentially activate
liver CD103+ DCs, leading to the sustained proliferation of adoptively
transferred, virus-specific CD8+ T cells. Collectively, these data suggest that
group 1 ILCs play a role in maintaining the liver as a tolerogenic site by
limiting the recruitment of peripheral NK cells during the early phase of viral
infection. Furthermore, our findings implicate that the inhibition of NKG2A
signaling on group 1 ILCs may be a novel vaccine strategy to induce robust CD8+ T
cell responses against persistent liver pathogens.
PMID- 27493246
TI - Interleukin-6 gene knockout antagonizes high-fat-induced trabecular bone loss.
AB - The purpose of the study was to determine the roles of interleukin-6 (IL6) in fat
and bone communication. Male wild-type (WT) mice and IL6 knockout (IL6(-/-)) mice
were fed with either regular diet (RD) or high-fat diet (HFD) for 12 weeks. Bone
mass and bone microstructure were evaluated by micro-computed tomography. Gene
expression related to lipid and bone metabolisms was assayed with real-time
quantitative polymerase chain reaction. Bone marrow cells from both genotypes
were induced to differentiate into osteoblasts or osteoclasts, and treated with
palmitic acid (PA). HFD increased the body weight and fat pad weight, and
impaired lipid metabolism in both WT and IL6(-/-) mice. The dysregulation of
lipid metabolism was more serious in IL6(-/-) mice. Trabecular bone volume
fraction, trabecular bone number and trabecular bone thickness were significantly
downregulated in WT mice after HFD than those in the RD (P < 0.05). However,
these bone microstructural parameters were increased by 53%, 34% and 40%,
respectively, in IL6(-/-) mice than those in WT mice on the HFD (P < 0.05). IL6(
/-) osteoblasts displayed higher alkaline phosphatase (ALP) activity and higher
mRNA levels of Runx2 and Colla1 than those in WT osteoblasts both in the control
and PA treatment group (P < 0.05). IL6(-/-) mice showed significantly lower mRNA
levels of PPARgamma and leptin and higher mRNA levels of adiponectin in
comparison with WT mice on HFD. In conclusion, these findings suggested that IL6
gene deficiency antagonized HFD-induced bone loss. IL6 might bridge lipid and
bone metabolisms and could be a new potential therapeutic target for lipid
metabolism disturbance-related bone loss.
PMID- 27493245
TI - beta-Arrestin 1-dependent regulation of Rap2 is required for fMLP-stimulated
chemotaxis in neutrophil-like HL-60 cells.
AB - beta-Arrestins have emerged as key regulators of cytoskeletal rearrangement that
are required for directed cell migration. Whereas it is known that beta-arrestins
are required for formyl-Met-Leu-Phe receptor (FPR) recycling, less is known about
their role in regulating FPR-mediated neutrophil chemotaxis. Here, we show that
beta-arrestin 1 (ArrB1) coaccumulated with F-actin within the leading edge of
neutrophil-like HL-60 cells during chemotaxis, and its knockdown resulted in
markedly reduced migration within fMLP gradients. The small GTPase Ras-related
protein 2 (Rap2) was found to bind ArrB1 under resting conditions but dissociated
upon fMLP stimulation. The FPR-dependent activation of Rap2 required ArrB1 but
was independent of Galphai activity. Significantly, depletion of either ArrB1 or
Rap2 resulted in reduced chemotaxis and defects in cellular repolarization within
fMLP gradients. These data strongly suggest a model in which FPR is able to
direct ArrB1 and other bound proteins that are required for lamellipodial
extension to the leading edge in migrating neutrophils, thereby orientating and
directing cell migration.
PMID- 27493247
TI - AMPK-dependent regulation of GLP1 expression in L-like cells.
AB - This study examined whether AMPK, an evolutionarily conserved sensor of cellular
energy status, determines the production of glucagon-like peptide-1 (GLP1). A
negative relation existed between phosphorylation of AMPKalpha and the expression
and secretion of GLP1 during changes in energy status in STC-1 cells, an L-like
cell line. High concentration of glucose (25 mmol/L) decreased AMPKalpha
phosphorylation, whereas it stimulated the expression and secretion of GLP1
relative to 5.6 mmol/L glucose. Serum starvation upregulated AMPKalpha
phosphorylation, whereas it reduced GLP1 production significantly. Stimulation of
AMPK phosphorylation by AICAR and overexpression of wild-type AMPKalpha1,
constitutively active AMPKalpha1 plasmids, or AMPKalpha1 lentivirus particles
suppressed proglucagon mRNA and protein contents in STC-1 cells. Inactivation of
AMPK by Compound C, AMPKalpha1 siRNA or kinase-inactive AMPKalpha1 mutant
increased the expression and secretion of GLP1. Our results suggest that
AMPKalpha1 may link energy supply with the production of GLP1 in L-like cells.
PMID- 27493243
TI - Autophagy in leukocytes and other cells: mechanisms, subsystem organization,
selectivity, and links to innate immunity.
AB - Autophagy is a fundamental biologic process that fulfills general and specialized
roles in cytoplasmic homeostasis. The cell-autonomous antimicrobial functions of
autophagy have been established in the macrophage. These cells and other
leukocytes continue to be the cells of choice in studying autophagy in immunity
and inflammation. This review uses several model examples that will be of
interest to leukocyte and cell biologists alike. Furthermore, it comprehensively
covers the subsystems in autophagy as they apply to all mammalian cells and
incorporates the recent progress in our understanding of how these modules come
together-a topic that should be of interest to all readers.
PMID- 27493248
TI - Vector Competence of Anopheles kleini and Anopheles sinensis (Diptera: Culicidae)
From the Republic of Korea to Vivax Malaria-Infected Blood From Patients From
Thailand.
AB - In total, 1,300 each of Anopheles kleini Rueda and Anopheles sinensis Wiedemann
sensu stricto (s.s.) females (colonized from the Republic of Korea) and Anopheles
dirus Peyton & Harrison (Thai strain) were allowed to feed on blood from Thai
malaria patients naturally infected with Plasmodium vivax The overall oocyst
infection rates for An. dirus, An. kleini, and An. sinensis s.s. were 77.4, 46.1,
and 45.9%, respectively. The mean number of oocysts was significantly higher for
An. dirus (82.7) compared with An. kleini (6.1) and An. sinensis s.s. (8.6),
whereas the mean number of oocysts for An. kleini and An. sinensis s.s. was
similar. The overall sporozoite infection rates for An. dirus, An. kleini, and
An. sinensis s.s. dissected on days 14-15, 21, and 28 days post-feed were
significantly higher for An. dirus (90.0%) than An. kleini (5.4%), whereas An.
kleini sporozoite rates were significantly higher than An. sinensis s.s. (<0.1%).
The overall sporozoite indices for positive females with +3 (100-1,000
sporozoites) and +4 (>1,000 sporozoites) salivary gland indices were
significantly higher for An. dirus (85.7%), compared with An. kleini (47.1%).
Only one An. sinensis s.s. had sporozoites (+2; >10-100 sporozoites). These
results indicate that An. kleini is a competent vector of vivax malaria. Although
An. sinensis s.s. develops relatively high numbers of oocysts, it is considered a
very poor vector of vivax malaria due to a salivary gland barrier.
PMID- 27493250
TI - Protein Self-Marking by Ectoparasites: A Case Study Using Bed Bugs (Hemiptera:
Cimicidae).
AB - The ability to mark individuals is a critical feature of many entomological
investigations, including dispersal studies. Insect dispersal is generally
investigated using mark-release-recapture techniques, whereby marked individuals
are released at a known location and then captured at a measured distance.
Ectoparasite dispersal has historically been challenging to study, in part
because of the ethical concerns associated with releasing marked individuals.
Here, we introduce the protein self-marking technique, whereby ectoparasites mark
themselves in the field by feeding on the blood of an introduced host. We
demonstrate the potential of this technique using laboratory-reared bed bugs
(Cimex lectularius L.) that marked themselves by feeding on either rabbit or
chicken blood. We then used enzyme-linked immunosorbent assays to detect host
specific blood serum proteins in bed bugs. We assessed these protein markers'
ability to 1) distinctively identify marked individuals, 2) persist following
multiple feedings on an alternate diet, 3) persist over time across a range of
temperatures, and 4) transfer from marked to unmarked individuals. Protein
markers were detectable in bed bugs before and after molting, remained detectible
after multiple feedings on an alternate diet, persisted regardless of whether an
individual was starved or fed on an alternate diet following original mark
acquisition, and did not transfer between individuals. The duration of
detectability depended on temperature. Our results suggest that protein self
marking is an effective technique for marking bed bugs and holds promise for use
in dispersal studies of ectoparasitic insects.
PMID- 27493249
TI - Mosquito Capture Rate Using CO2-Baited Traps in Relation to Distance From Water
and Height: Implications for Avian Disease Transmission.
AB - Accumulating evidence suggests that enzootic transmission of pathogens such as
West Nile virus (WNV) by mosquitoes is governed by host-bird interactions,
including mosquito preferences for specific species and developmental stages of
host birds, host bird availability, and host defensive behavior. Here, we
examined how the attack rate of five mosquito species in southern California was
influenced by the position of CO2-baited traps in relation to distance from water
and trap height. We identified 44,207 female mosquitoes representing five
species: Aedes vexans Meigen, Anopheles franciscanus McCracken, Anopheles hermsi
Barr & Guptavanij, and the two most abundant species which are also WNV vectors,
Culex erythrothorax Dyar and Culex tarsalis Coquillett. Mosquito captures
decreased markedly with trap height, and also decreased with distance from a
riparian area but not with distance from an open water source lacking a vegetated
border. The results of this study suggest that WNV-competent ornithophilic
mosquitoes may amplify the virus especially in reservoir birds that roost or nest
close to the ground and near riparian vegetation.
PMID- 27493251
TI - Bionomics and Vector Potential of Culex thriambus (Diptera: Culicidae) Mosquitoes
in Lake County, California.
AB - California statewide West Nile virus (WNV) minimum infection rates in Culex
thriambus Dyar mosquitoes are high; however, few specimens are submitted and
tested each year, as their distribution seems limited to larval habitats along
riparian systems. To evaluate the role of Cx. thriambus in the amplification,
maintenance, and overwintering of WNV in Lake County, CA, the bionomics and
vector potential of the species was investigated during 2014 and 2015. Culex
thriambus was the most abundant mosquito species, with 1,153 adults and 7,624
immatures collected by vacuum aspiration and dip sampling, respectively, at the
primary study site. Detection of WNV in four mosquito pools during September
through November coincided with peak seasonality. Females entered and maintained
a reproductive diapause during winter under field and seminatural conditions.
Diapause was initiated in the majority of Cx. thriambus females by October and
was terminated by 30 March. Some parous females (7.1%) and those in host-seeking
arrest (7.1%) were collected throughout the winter period. An accrual of 679.51
degree-days ( degrees D) was necessary for diapause termination under seminatural
conditions. Culex thriambus females fed on 16 different avian species during
spring and summer, and no mammalian feeds were detected. West Nile viral RNA was
detected in four of 42 Cx. thriambus pools tested during June through November
and infection rates ranged from 3.53-28.15/1,000 tested. In summary, WNV
transmission may be increased along riparian corridors throughout California
where Cx. thriambus mosquitoes remain relatively abundant.
PMID- 27493252
TI - Knockdown Resistance Mutations in Aedes aegypti (Diptera: Culicidae) From Puerto
Rico.
AB - Permethrin resistance is widespread in Aedes aegypti (L.), the main dengue, zika,
and chikungunya virus vector in Latin America and the Caribbean. A common
mechanism of resistance to pyrethroids-knockdown resistance (kdr)-is conferred
through mutations in the insect's voltage-dependent sodium channel. In this
mosquito, around 10 replacement substitutions in the voltage-gated sodium channel
gene (vgsc) have been reported in pyrethroid-resistant strains. Two of these
mutations, named Ile1,016 and Cys1,534, are widespread in mosquito populations
from Latin America and the Caribbean. This study assessed the levels of
permethrin resistance and the frequency of two kdr mutations in eight Ae. aegypti
populations collected in Puerto Rico in 2013. Permethrin resistance factors
ranged from 33-214-fold relative to the New Orleans reference strain. The
frequency of kdr mutation Ile1,016 ranged from 0.65 to fixation (1.0), and for
Cys1,534 frequencies varied from 0.8 to fixation. Alarmingly, two populations
Carolina and Caguas-reached fixation at both loci. Our results suggest that
permethrin effectiveness for Ae. aegypti control is compromised in these
collections from Puerto Rico.
PMID- 27493253
TI - Coexistence of Aedes aegypti and Aedes albopictus (Diptera: Culicidae) in
Peninsular Florida Two Decades After Competitive Displacements.
AB - The spread of Aedes albopictus (Skuse) eastward in the mid-1980s from its initial
establishment in Houston, TX, was associated with rapid declines and local
disappearances of Aedes aegypti (L.) in Gulf Coast states and Florida where
annual larval surveillance during the early 1990s described temporal and spatial
patterns of competitive displacements in cemeteries and tire shops. Approximately
20 yr later in 2013-2014, we re-visited former collection sites and sampled
aquatic immatures of these two species from tire shops in 10 cities on State
Route 441 and from 9 cemeteries from Lakeland to Miami in southwest Florida. In
the recent samples Ae. aegypti was recovered from three central Florida cities
where it had not been detected in 1994, but its northern limit on Rte. 441,
Apopka, did not change. Other evidence, such as trends at a few cemeteries,
suggested a moderate resurgence of this species since 1994. Cage experiments that
exposed female progeny of Ae. aegypti from recent Florida collection sites to
interspecific mating by Ae. albopictus males showed that females from coexistence
sites had evolved resistance to cross-mating, but Ae. aegypti from sites with no
Ae. albopictus were relatively susceptible to satyrization. Habitat
classifications of collection sites were reduced by principal component (PC)
analysis to four variables that accounted for > 99% of variances; PCs with strong
positive loadings for tree cover and ground vegetation were associated with
collection sites yielding only Ae. albopictus Within the coexistence range of the
two species, the numbers of Ae. aegypti among total Aedes collected were strongly
correlated in stepwise logistic regression models with two habitat-derived PCs,
distance from the coast, and annual rainfall and mean maximum temperatures at the
nearest weather station. Subtle increases in the range of Ae. aegypti since its
previous displacements are interpreted in the context of the evolution of
resistance to mating interference, realized versus fundamental niches of the two
species, and persisting competition with Ae. albopictus.
PMID- 27493254
TI - Predicting the Functionality and Form of a Dialysis Fistula.
PMID- 27493255
TI - Value of Donor-Specific Anti-HLA Antibody Monitoring and Characterization for
Risk Stratification of Kidney Allograft Loss.
AB - The diagnosis system for allograft loss lacks accurate individual risk
stratification on the basis of donor-specific anti-HLA antibody (anti-HLA DSA)
characterization. We investigated whether systematic monitoring of DSA with
extensive characterization increases performance in predicting kidney allograft
loss. This prospective study included 851 kidney recipients transplanted between
2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2
years post-transplant, and the time of post-transplant clinical events. We
assessed DSA characteristics and performed systematic allograft biopsies at the
time of post-transplant serum evaluation. At transplant, 110 (12.9%) patients had
DSAs; post-transplant screening identified 186 (21.9%) DSA-positive patients.
Post-transplant DSA monitoring improved the prediction of allograft loss when
added to a model that included traditional determinants of allograft loss
(increase in c statistic from 0.67; 95% confidence interval [95% CI], 0.62 to
0.73 to 0.72; 95% CI, 0.67 to 0.77). Addition of DSA IgG3 positivity or C1q
binding capacity increased discrimination performance of the traditional model at
transplant and post-transplant. Compared with DSA mean fluorescence intensity,
DSA IgG3 positivity and C1q binding capacity adequately reclassified patients at
lower or higher risk for allograft loss at transplant (category-free net
reclassification index, 1.30; 95% CI, 0.94 to 1.67; P<0.001 and 0.93; 95% CI,
0.49 to 1.36; P<0.001, respectively) and post-transplant (category-free net
reclassification index, 1.33; 95% CI, 1.03 to 1.62; P<0.001 and 0.95; 95% CI,
0.62 to 1.28; P<0.001, respectively). Thus, pre- and post-transplant DSA
monitoring and characterization may improve individual risk stratification for
kidney allograft loss.
PMID- 27493256
TI - Preserving Residual Kidney Function in Hemodialysis Patients-Back in the
Spotlight.
PMID- 27493257
TI - Heme Oxygenase-1 Gene Polymorphisms-Toward Precision Medicine for AKI.
PMID- 27493258
TI - Coronary Revascularization in Patients with CKD Stage 5D: Pragmatic
Considerations.
AB - Coronary revascularization decisions for patients with CKD stage 5D present a
dilemma for clinicians because of high baseline risks of mortality and future
cardiovascular events. This population differs from the general population
regarding characteristics of coronary plaque composition and behavior, accuracy
of noninvasive testing, and response to surgical and percutaneous
revascularization, such that findings from the general population cannot be
automatically extrapolated. However, this high-risk population has been excluded
from all randomized trials evaluating outcomes of revascularization.
Observational studies have attempted to address long-term outcomes after surgical
versus percutaneous revascularization strategies, but inherent selection bias may
limit accuracy. Compared with percutaneous strategies, surgical revascularization
seems to have long-term survival benefit on the basis of observational data but
associates with substantially higher short-term mortality rates. Percutaneous
revascularization with drug-eluting and bare metal stents associates with a high
risk of in-stent restenosis and need for future revascularization, perhaps
contributing to the higher long-term mortality hazard. Off-pump coronary bypass
surgery and the newest generation of drug-eluting stent platforms offer no
definitive benefits. In this review, we address the nuances, complexities, and
tradeoffs that clinicians face in determining the optimal method of coronary
revascularization for this high-risk population.
PMID- 27493260
TI - 18F-FDG PET/CT Imaging of Primary Gastric Lymphoma.
AB - Primary gastric lymphoma (PGL) accounts for less than 4% of gastric neoplasms.
18F-FDG PET with simultaneously acquired CT (18F-FDG PET/CT) allows for staging
and differentiation from other gastric cancers. Rapid diagnosis and staging are
important because chemotherapeutic response is generally favorable. We describe a
case of an 83-y-old woman with stage II1 PGL. 18F-FDG PET/CT can be helpful to
differentiate various gastric masses and is an important factor in the staging of
PGL.
PMID- 27493259
TI - Variable Cyst Development in Autosomal Dominant Polycystic Kidney Disease: The
Biologic Context.
AB - Patients with autosomal dominant polycystic kidney disease (ADPKD) typically
carry a mutation in either the PKD1 or PKD2 gene, which leads to massive cyst
formation in both kidneys. However, the large intrafamilial variation in the
progression rate of ADPKD suggests involvement of additional factors other than
the type of mutation. The identification of these factors will increase our
understanding of ADPKD and could ultimately help in the development of a
clinically relevant therapy. Our review addresses the mechanisms by which various
biologic processes influence cyst formation and cyst growth, thereby explaining
an important part of the inter- and intrafamilial variability in ADPKD. Numerous
studies from many laboratories provide compelling evidence for the influence on
cyst formation by spatiotemporal gene inactivation, the genetic context, the
metabolic status, the presence of existing cysts, and whether the kidneys were
challenged by renal injury. Collectively, a solid basis is provided for the
concept that the probability of cyst formation is determined by functional PKD
protein levels and the biologic context. We model these findings in a graphic
representation called the cystic probability landscape, providing a robust
conceptual understanding of why cells sometimes do or do not form cysts.
PMID- 27493261
TI - Scintigraphic Diagnosis of Intrathoracic Splenic Implants Masquerading as
Malignancy.
AB - After significant trauma to the spleen, small viable splenic fragments may exist
in the peritoneal cavity or, less commonly, in the thorax. Thus, the appearance
of splenules within the thorax on CT images can easily be mistaken for malignancy
and lead to unnecessary intervention. Here, we present a case of multiple
pulmonary masses that initially were presumed to be malignancy, leading to CT
guided biopsy, but were eventually confirmed to be thoracic splenules through
99mTc-labeled sulfur colloid scintigraphy.
PMID- 27493262
TI - Grouping of Metastatic Thyroid Carcinoma by Molecular Imaging Features to Allow
for Individualized Treatment, with Emphasis on the TENIS Syndrome.
AB - The process of radioiodine ((131)I) refractoriness, dedifferentiation, and
development of thyroglobulin elevation and negative iodine scintigraphy (TENIS)
syndrome in metastatic differentiated thyroid carcinoma (DTC) could be viewed as
a disease continuum rather than a single event or an all-or-none phenomenon. In
this report, the important role of molecular functional imaging in systematically
exploring the disease biology and course of metastatic DTC is presented. Making
this role the base, this report proposes a novel clinical classification for
TENIS syndrome using molecular functional imaging. Such an endeavor, in our view,
would aid in classification into subgroups and development of an individualized
treatment strategy for patients with metastatic DTC. Case illustrations are
presented that substantiate this viewpoint, including the value of combined
assessment in selected cases and the requirement of a multipronged treatment
approach for certain case scenarios. In addition to multiple other
considerations, we believe that molecular functional imaging-based
characterization of metastatic lesions could evolve as an important determinant
for defining the optimal treatment strategy in patients with metastatic DTC,
making the clinical management more rational and scientific.
PMID- 27493263
TI - Increased Gastric Activity on Myocardial Perfusion Imaging.
AB - We anecdotally observed an increased accumulation of (99m)Tc-tetrofosmin in the
stomach of myocardial perfusion patients when their uptake phase coincided with
preparation of hamburgers in an adjacent room for gastric emptying studies on
other patients. The potential for a scent-stimulated alteration of gastric
biodistribution required further investigation. METHODS: An experimental group
and a control group were enrolled (20 patients per group). The experimental group
could smell food being prepared during the uptake phase. Stomach, heart, and
background regions were drawn in multiple projections, and the resulting data
were evaluated. RESULTS: The experimental and control groups did not
significantly differ in stomach counts per pixel, background-corrected counts per
pixel, or heart-to-stomach ratio. Further analysis of the data revealed that
women had a significantly higher increase in stomach counts (P = 0.022) and
background-corrected stomach counts (P = 0.018) than men. CONCLUSION: Women had a
greater increase in gastric (99m)Tc-tetrofosmin activity than men during the
radiopharmaceutical uptake phase, but there was no causal relationship between an
increase in activity and olfactory stimulation from the cooking of food.
PMID- 27493264
TI - Subjecting Radiologic Imaging to the Linear No-Threshold Hypothesis: A Non
Sequitur of Non-Trivial Proportion.
AB - Radiologic imaging is claimed to carry an iatrogenic risk of cancer, based on an
uninformed commitment to the 70-y-old linear no-threshold hypothesis (LNTH).
Credible evidence of imaging-related low-dose (<100 mGy) carcinogenic risk is
nonexistent; it is a hypothetical risk derived from the demonstrably false LNTH.
On the contrary, low-dose radiation does not cause, but more likely helps
prevent, cancer. The LNTH and its offspring, ALARA (as low as reasonably
achievable), are fatally flawed, focusing only on molecular damage while ignoring
protective, organismal biologic responses. Although some grant the absence of low
dose harm, they nevertheless advocate the "prudence" of dose optimization (i.e.,
using ALARA doses); but this is a radiophobia-centered, not scientific, approach.
Medical imaging studies achieve a diagnostic purpose and should be governed by
the highest science-based principles and policies. The LNTH is an invalidated
hypothesis, and its use, in the form of ALARA dosing, is responsible for
misguided concerns promoting radiophobia, leading to actual risks far greater
than the hypothetical carcinogenic risk purportedly avoided. Further, the myriad
benefits of imaging are ignored. The present work calls for ending the
radiophobia caused by those asserting the need for dose optimization in imaging:
the low-dose radiation of medical imaging has no documented pathway to harm,
whereas the LNTH and ALARA most assuredly do.
PMID- 27493265
TI - Reply: 68Ga-DOTATATE PET/CT Versus MRI: Why the Comparison of 68Ga-DOTATATE
PET/CT to an Appropriate MRI Protocol Is Essential.
PMID- 27493266
TI - Liposomal Treatment of Experimental Arthritis Can Be Monitored Noninvasively with
a Radiolabeled Anti-Fibroblast Activation Protein Antibody.
AB - : Rheumatoid arthritis is a chronic autoimmune disorder resulting in synovial
inflammation. Fibroblast activation protein (FAP) is overexpressed by
fibroblastlike synoviocytes in arthritic joints. Radioimmunoimaging with an anti
FAP antibody might be used to monitor the response to therapy, thus enabling
tailored therapy strategies and therapeutic outcomes. The aim of this study was
to assess whether a radiolabeled anti-FAP antibody could be used to monitor the
efficacy of treatment with long-circulating liposomes (LCL) containing
prednisolone phosphate (PLP-LCL) in a mouse model of arthritis. METHODS: Collagen
induced arthritis (CIA) was induced in male DBA/1J mice. Mice were treated with a
single injection (10 mg/kg) of PLP-LCL or empty LCL as a control. SPECT and CT
images were acquired 24 h after injection of 99mTc-labeled succinimidyl
hydrazinonicotinamide (99mTc-S-HYNIC)-conjugated anti-FAP antibody 28H1 at 2, 5,
and 9 d after treatment. The uptake of 99mTc-S-HYNIC-28H1 in all joints was
quantified and correlated with macroscopic arthritis scores. RESULTS: Treatment
of CIA with PLP-LCL significantly suppressed joint swelling. At just 1 d after
treatment, the macroscopic arthritis scores had decreased by 50%. Scores
decreased further, to only 10% of the initial scores, at 5 and 9 d after
treatment. In contrast, macroscopic arthritis scores had increased up to 600% in
untreated mice at 9 d after the injection of empty LCL. 99mTc-S-HYNIC-28H1 uptake
ranged from 1.5 percentage injected dose per gram in noninflamed joints to 22.6
percentage injected dose per gram in severely inflamed joints. The uptake of
radiolabeled 28H1 in inflamed joints (percentage injected dose) correlated with
the arthritis score (Spearman rho, 0.77; P < 0.0001). Moreover, the uptake of
99mTc-S-HYNIC-28H1 was slightly increased at 9 d after therapy but was not seen
macroscopically, indicating that SPECT/CT imaging might be more sensitive than
the macroscopic arthritis scoring method. CONCLUSION: SPECT/CT imaging with 99mTc
S-HYNIC-28H1 specifically monitored the response to therapy, and tracer
accumulation correlated with the severity of inflammation. In addition, SPECT/CT
imaging was potentially more sensitive than the macroscopic arthritis scoring
method. This study showed that SPECT/CT with 99mTc-S-HYNIC-28H1 could be used to
noninvasively monitor the course of CIA in mice.
PMID- 27493267
TI - Clinical Translation of a Dual Integrin alphavbeta3- and Gastrin-Releasing
Peptide Receptor-Targeting PET Radiotracer, 68Ga-BBN-RGD.
AB - : This study aimed to document the first-in-human application of a 68Ga-labeled
heterodimeric peptide BBN-RGD (bombesin-RGD) that targets both integrin
alphavbeta3 and gastrin-releasing peptide receptor (GRPR). We evaluated the
safety and assessed the clinical diagnostic value of 68Ga-BBN-RGD PET/CT in
prostate cancer patients in comparison with 68Ga-BBN. METHODS: Five healthy
volunteers (4 men and 1 woman; age range, 28-53 y) were enrolled to validate the
safety of 68Ga-BBN-RGD. Dosimetry was calculated using the OLINDA/EXM software.
Thirteen patients with prostate cancer (4 newly diagnosed and 9 posttherapy) were
enrolled. All the patients underwent PET/CT scans 15-30 min after intravenous
injection of 1.85 MBq (0.05 mCi) per kilogram of body weight of 68Ga-BBN-RGD and
also accepted 68Ga-BBN PET/CT within 2 wk for comparison. RESULTS: With a mean
injected dose of 107.3 +/- 14.8 MBq per patient, no side effect was found during
the whole procedure and 2 wk follow-up, demonstrating the safety of 68Ga-BBN-RGD.
A patient would be exposed to a radiation dose of 2.90 mSv with an injected dose
of 129.5 MBq (3.5 mCi), which is much lower than the dose limit set by the Food
and Drug Administration. In 13 patients with prostate cancer diagnosed by biopsy,
68Ga-BBN-RGD PET/CT detected 3 of 4 primary tumors, 14 metastatic lymph nodes,
and 20 bone lesions with an SUVmax of 4.46 +/- 0.50, 6.26 +/- 2.95, and 4.84 +/-
1.57, respectively. Only 2 of 4 primary tumors, 5 lymph nodes, and 12 bone
lesions were positive on 68Ga-BBN PET/CT, with the SUVmax of 2.98 +/- 1.24, 4.17
+/- 1.89, and 3.61 +/- 1.85, respectively. CONCLUSION: This study indicates the
safety and efficiency of a new type of dual integrin alphavbeta3- and GRPR
targeting PET radiotracer in prostate cancer diagnosis and staging.
PMID- 27493268
TI - In Vivo Imaging of Antileukemic Drug Asparaginase Reveals a Rapid Macrophage
Mediated Clearance from the Bone Marrow.
AB - : The antileukemic drug asparaginase, a key component in the treatment of acute
lymphoblastic leukemia, acts by depleting asparagine from the blood. However,
little is known about its pharmacokinetics, and mechanisms of therapy resistance
are poorly understood. Here, we explored the in vivo biodistribution of
radiolabeled asparaginase, using a combination of imaging and biochemical
techniques, and provide evidence for tissue-specific clearance mechanisms, which
could reduce the effectiveness of the drug at these specific sites. METHODS: In
vivo localization of 111In-labeled Escherichia coli asparaginase was performed in
C57BL/6 mice by both small-animal SPECT/CT and ex vivo biodistribution studies.
Mice were treated with liposomal clodronate to investigate the effect of
macrophage depletion on tracer localization and drug clearance in vivo. Moreover,
macrophage cell line models RAW264.7 and THP-1, as well as knockout mice, were
used to identify the cellular and molecular components controlling asparaginase
pharmacokinetics. RESULTS: In vivo imaging and biodistribution studies showed a
rapid accumulation of asparaginase in macrophage-rich tissues such as the liver,
spleen, and in particular bone marrow. Clodronate-mediated depletion of
phagocytic cells markedly prolonged the serum half-life of asparaginase in vivo
and decreased drug uptake in these macrophage-rich organs. Immunohistochemistry
and in vitro binding assays confirmed the involvement of macrophagelike cells in
the uptake of asparaginase. We identified the activity of the lysosomal protease
cathepsin B in macrophages as a rate-limiting factor in degrading asparaginase
both in vitro and in vivo. CONCLUSION: We showed that asparaginase is rapidly
cleared from the serum by liver-, spleen-, and bone marrow-resident phagocytic
cells. As a consequence of this efficient uptake and protease-mediated
degradation, particularly bone marrow-resident macrophages may provide a
protective niche to leukemic cells.
PMID- 27493269
TI - Strategies to Inhibit ABCB1- and ABCG2-Mediated Efflux Transport of Erlotinib at
the Blood-Brain Barrier: A PET Study on Nonhuman Primates.
AB - : The tyrosine kinase inhibitor erlotinib poorly penetrates the blood-brain
barrier (BBB) because of efflux transport by P-glycoprotein (ABCB1) and breast
cancer resistance protein (ABCG2), thereby limiting its utility in the treatment
of non-small cell lung cancer metastases in the brain. Pharmacologic strategies
to inhibit ABCB1/ABCG2-mediated efflux transport at the BBB have been
successfully developed in rodents, but it remains unclear whether these can be
translated to humans given the pronounced species differences in ABCG2/ABCB1
expression ratios at the BBB. We assessed the efficacy of two different
ABCB1/ABCG2 inhibitors to enhance brain distribution of 11C-erlotinib in nonhuman
primates as a model of the human BBB. METHODS: Papio anubis baboons underwent PET
scans of the brain after intravenous injection of 11C-erlotinib under baseline
conditions (n = 4) and during intravenous infusion of high-dose erlotinib (10
mg/kg/h, n = 4) or elacridar (12 mg/kg/h, n = 3). RESULTS: Under baseline
conditions, 11C-erlotinib distribution to the brain (total volume of distribution
[VT], 0.22 +/- 0.015 mL/cm3) was markedly lower than its distribution to muscle
tissue surrounding the skull (VT, 0.86 +/- 0.10 mL/cm3). Elacridar infusion
resulted in a 3.5 +/- 0.9-fold increase in 11C-erlotinib distribution to the
brain (VT, 0.81 +/- 0.21 mL/cm3, P < 0.01), reaching levels comparable to those
in muscle tissue, without changing 11C-erlotinib plasma pharmacokinetics. During
high-dose erlotinib infusion, 11C-erlotinib brain distribution was also
significantly (1.7 +/- 0.2-fold) increased (VT, 0.38 +/- 0.033 mL/cm3, P < 0.05),
with a concomitant increase in 11C-erlotinib plasma exposure. CONCLUSION: We
successfully implemented ABCB1/ABCG2 inhibition protocols in nonhuman primates
resulting in pronounced increases in brain distribution of 11C-erlotinib. For
patients with brain tumors, such inhibition protocols may ultimately be applied
to create more effective treatments using drugs that undergo efflux transport at
the BBB.
PMID- 27493271
TI - TERT Promoter Mutation Predicts Radioiodine-Refractory Character in Distant
Metastatic Differentiated Thyroid Cancer.
AB - : Telomerase reverse transcriptase (TERT) promoter mutation has been reported to
be associated with aggressive characteristics in differentiated thyroid cancer
(DTC). This study examined the status of TERT mutation in distant metastatic DTC
and evaluated the correlation between TERT mutation and radioiodine uptake, as
well as that between TERT mutation and therapy response. METHODS: TERT promoter
and B-Raf proto-oncogene (BRAF) V600E mutation were retrospectively examined in
primary tumors of 66 patients with distant metastatic DTC. Stimulated
thyroglobulin (sTg) changes, radioiodine uptake status (avid or nonavid), and
other imaging evidence were analyzed to evaluate therapy response. After a median
follow-up of 46.5 mo (interquartile range, 29.0-70.5 mo), therapy response was
classified as either disease control or refractory. RESULTS: The prevalence of
TERT mutations was 22.73% (15/66), of which C228T mutation was more prevalent
(13/15) than C250T mutation (2/15). Rising sTg was noticed in 93.33% (14/15) of
the TERT mutation group. Of cases negative for both mutations, 78.12% (25/32)
presented with decreased sTg. TERT mutation closely correlated with a poor
response to radioiodine therapy (P < 0.001), and all 15 patients were classified
as refractory to radioiodine therapy, with a positive predictive value of 100% at
the endpoint of follow-up. TERT mutation was associated with older mean age at
diagnosis (P < 0.001), larger mean tumor diameter (P = 0.013), and greater
likelihood of both BRAF mutation coexistence (P = 0.044) and radioiodine
refractory character (P < 0.001). In the 36 cases whose imaging results underwent
semiquantitative analysis, TERT mutation significantly correlated with non
radioiodine avidity, with a much lower mean tumor-to-background ratio (obtained
from postradioiodine whole-body scanning) than in TERT wild-type cases (P <
0.001). In addition, patients with distant metastatic DTC with TERT mutation were
more likely to lose radioiodine avidity at the initial radioiodine therapy than
were those with only BRAF mutation (8/8 vs. 5/11; Fisher exact test, P = 0.018).
CONCLUSION: TERT mutation closely associates with non-radioiodine avidity in
distant metastatic DTC, and when compared with BRAF mutation, TERT mutation
manifested a greater negative influence on radioiodine uptake. TERT mutation
could also be used as an early predictor of radioiodine-refractory cases.
PMID- 27493270
TI - Tumor-Absorbed Dose for Non-Hodgkin Lymphoma Patients Treated with the Anti-CD37
Antibody Radionuclide Conjugate 177Lu-Lilotomab Satetraxetan.
AB - : 177Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate
currently tested in a phase 1/2a first-in-human dosage escalation trial for
patients with relapsed CD37+ indolent non-Hodgkin lymphoma. The aim of this work
was to develop dosimetric methods and calculate tumor-absorbed radiation doses
for patients treated with 177Lu-lilotomab satetraxetan. METHODS: Patients were
treated at escalating injected activities (10, 15 and 20 MBq/kg) of 177Lu
lilotomab satetraxetan and with different predosing, with or without 40 mg of
unlabeled lilotomab. Eight patients were included for the tumor dosimetry study.
Tumor radioactivity concentrations were calculated from SPECT acquisitions at
multiple time points, and tumor masses were delineated from corresponding CT
scans. Tumor-absorbed doses were then calculated using the OLINDA sphere model.
To perform voxel dosimetry, the SPECT/CT data and an in-house-developed MATLAB
program were combined to investigate the dose rate homogeneity. RESULTS: Twenty
six tumors in 8 patients were ascribed a mean tumor-absorbed dose. Absorbed doses
ranged from 75 to 794 cGy, with a median of 264 cGy across different dosage
levels and different predosing. A significant correlation between the dosage
level and tumor-absorbed dose was found. Twenty-one tumors were included for
voxel dosimetry and parameters describing dose-volume coverage calculated. The
investigation of intratumor voxel doses indicates that mean tumor dose is
correlated to these parameters. CONCLUSION: Tumor-absorbed doses for patients
treated with 177Lu-lilotomab satetraxetan are comparable to doses reported for
other radioimmunotherapy compounds. Although the intertumor variability was
considerable, a correlation between tumor dose and patient dosage level was
found. Our results indicate that mean dose may be used as the sole dosimetric
parameter on the lesion level.
PMID- 27493272
TI - Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide
Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results.
AB - : We recently introduced the potent gastrin-releasing peptide receptor (GRPR)
antagonist 68Ga-SB3 (68Ga-DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp
Ala-Val-Gly-His-Leu-NHEt), showing excellent tumor localizing efficacy in animal
models and in patients. By replacement of the C-terminal Leu13-Met14-NH2
dipeptide of SB3 by Sta13-Leu14-NH2, the novel GRPR antagonist NeoBOMB1 was
generated and labeled with different radiometals for theranostic use. We herein
report on the biologic profile of resulting 67/68Ga-, 111In-, and 177Lu-NeoBOMB1
radioligands in GRPR-expressing cells and mouse models. The first evidence of
prostate cancer lesion visualization in men using 68Ga-NeoBOMB1 and PET/CT is
also presented. METHODS: NeoBOMB1 was radiolabeled with 67/68Ga, 111In, and 177Lu
according to published protocols. The respective metalated species natGa-, natIn
, and natLu-NeoBOMB1 were also synthesized and used in competition binding
experiments against [125I-Tyr4]BBN in GRPR-positive PC-3 cell membranes.
Internalization of 67Ga-, 111In-, and 177Lu-NeoBOMB1 radioligands was studied in
PC-3 cells at 37 degrees C, and their metabolic stability in peripheral mouse
blood was determined by high-performance liquid chromatography analysis of blood
samples. Biodistribution was performed by injecting a 67Ga-, 111In-, or 177Lu
NeoBOMB1 bolus (74, 74, or 370 kBq, respectively, 100 MUL, 10 pmol total peptide
+/- 40 nmol Tyr4-BBN: for in vivo GRPR blockade) in severe combined
immunodeficiency mice bearing PC-3 xenografts. PET/CT images with 68Ga-NeoBOMB1
were acquired in prostate cancer patients. RESULTS: NeoBOMB1 and natGa-, natIn-,
and natLu-NeoBOMB1 bound to GRPR with high affinity (half maximal inhibitory
concentration, 1-2 nM). 67Ga-, 111In-, and 177Lu-NeoBOMB1 specifically and
strongly bound on the cell membrane of PC-3 cells displaying low internalization,
as expected for receptor antagonists. They showed excellent metabolic stability
in peripheral mouse blood (>95% intact at 5 min after injection). After injection
in mice, all 3 (67Ga-, 111In-, and 177Lu-NeoBOMB1) showed comparably high and
GRPR-specific uptake in the PC-3 xenografts (e.g., 30.6 +/- 3.9, 28.6 +/- 6.0,
and >35 percentage injected dose per gram at 4 h after injection, respectively),
clearing from background predominantly via the kidneys. During a translational
study in prostate cancer patients, 68Ga-NeoBOMB1 rapidly localized in pathologic
lesions, achieving high-contrast imaging. CONCLUSION: The GRPR antagonist
radioligands 67Ga-, 111In-, and 177Lu-NeoBOMB1, independent of the radiometal
applied, have shown comparable behavior in prostate cancer models, in favor of
future theranostic use in GRPR-positive cancer patients. Such translational
prospects were further supported by the successful visualization of prostate
cancer lesions in men using 68Ga-NeoBOMB1 and PET/CT.
PMID- 27493273
TI - Preclinical Pharmacokinetics and Biodistribution Studies of 89Zr-Labeled
Pembrolizumab.
AB - : Pembrolizumab is a humanized monoclonal antibody targeting programmed cell
death protein 1 (PD-1) found on T and pro-B cells. Pembrolizumab prevents PD-1
ligation by both PD-L1 and PD-L2, preventing the immune dysregulation that
otherwise occurs when T-cells encounter cells expressing these ligands.
Clinically, PD-1 blockade elicits potent antitumor immune responses, and
antibodies blocking PD-1 ligation, including pembrolizumab, have recently
received Food and Drug Administration approval for the treatment of advanced
melanoma, renal cell cancer, and non-small cell lung cancer. METHODS: In this
study, we evaluated the pharmacokinetics, biodistribution, and dosimetry of
pembrolizumab in vivo, accomplished through radiolabeling with the positron
emitter 89Zr. PET imaging was used to evaluate the whole-body distribution of
89Zr-deferoxamine (Df)-pembrolizumab in two rodent models (mice and rats). Data
obtained from PET scans and biodistribution studies were extrapolated to humans
to estimate the dosimetry of the tracer. As a proof of concept, the
biodistribution of 89Zr-Df-pembrolizumab was further investigated in a humanized
murine model. RESULTS: The tracer remained stable in blood circulation throughout
the study and accumulated the greatest in liver and spleen tissues. Both mice and
rats showed similar biodistribution and pharmacokinetics of 89Zr-Df
pembrolizumab. In the humanized mouse model, T-cell infiltration into the
salivary and lacrimal glands could be successfully visualized. CONCLUSION: These
data will augment our understanding of the pharmacokinetics and biodistribution
of radiolabeled pembrolizumab in vivo, while providing detailed dosimetry data
that may lead to better dosing strategies in the future. These findings further
demonstrate the utility of noninvasive in vivo PET imaging to dynamically track T
cell checkpoint receptor expression and localization in a humanized mouse model.
PMID- 27493275
TI - Lock-in camera based heterodyne holography for ultrasound-modulated optical
tomography inside dynamic scattering media.
AB - Ultrasound-modulated optical tomography (UOT) images optical contrast deep inside
scattering media. Heterodyne holography based UOT is a promising technique that
uses a camera for parallel speckle detection. In previous works, the speed of
data acquisition was limited by the low frame rates of conventional cameras. In
addition, when the signal-to-background ratio was low, these cameras wasted most
of their bits representing an informationless background, resulting in extremely
low efficiencies in the use of bits. Here, using a lock-in camera, we increase
the bit efficiency and reduce the data transfer load by digitizing only the
signal after rejecting the background. Moreover, compared with the conventional
four-frame based amplitude measurement method, our single-frame method is more
immune to speckle decorrelation. Using lock-in camera based UOT with an
integration time of 286 MUs, we imaged an absorptive object buried inside a
dynamic scattering medium exhibiting a speckle correlation time ([Formula: see
text]) as short as 26 MUs. Since our method can tolerate speckle decorrelation
faster than that found in living biological tissue ([Formula: see text] ~ 100
1000 MUs), it is promising for in vivo deep tissue non-invasive imaging.
PMID- 27493274
TI - Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine,
MDPV, and Caffeine.
AB - Illicit drug preparations often include more than one pharmacologically active
compound. For example, cocaine and synthetic cathinones [e.g., 3,4
methylenedioxypyrovalerone (MDPV)] are often mixed with caffeine before sale.
Caffeine is likely added to these preparations because it is inexpensive and
legal; however, caffeine might also mimic or enhance some of the effects of
cocaine or MDPV. In these studies, male Sprague-Dawley rats were trained to
discriminate 10 mg/kg cocaine from saline, and the discriminative stimulus
effects of cocaine, caffeine, and MDPV were evaluated alone and as binary
mixtures (cocaine and caffeine, MDPV and caffeine, and cocaine and MDPV) at fixed
dose ratios of 3:1, 1:1, and 1:3 relative to the dose of each drug that produced
50% cocaine-appropriate responding. Dose-addition analyses were used to determine
the nature of the drug-drug interactions for each mixture (e.g., additive, supra
additive, or subadditive). Although additive interactions were observed for most
mixtures, supra-additive interactions were observed at the 50% effect level for
the 1:1 mixture of cocaine and caffeine and at the 80% effect level for all three
mixtures of cocaine and caffeine, as well as for the 3:1 and 1:3 mixtures of
cocaine and MDPV. These results demonstrate that with respect to cocaine-like
discriminative stimulus effects, caffeine can function as a substitute in drug
preparations containing either cocaine or MDPV, with enhancements of cocaine-like
effects possible under certain conditions. Further research is needed to
determine whether similar interactions exist for other abuse-related or toxic
effects of drug preparations, including cocaine, synthetic cathinones, and
caffeine.
PMID- 27493276
TI - Air-coupled acoustic radiation force for non-contact generation of broadband
mechanical waves in soft media.
AB - A non-contact method for efficient, non-invasive excitation of mechanical waves
in soft media is proposed, in which we focus an ultrasound (US) signal through
air onto the surface of a medium under study. The US wave reflected from the
air/medium interface provides radiation force to the medium surface that launches
a transient mechanical wave in the transverse (lateral) direction. The type of
mechanical wave is determined by boundary conditions. To prove this concept, a
home-made 1 MHz piezo-ceramic transducer with a matching layer to air sends a
chirped US signal centered at 1 MHz to a 1.6 mm thick gelatin phantom mimicking
soft biological tissue. A phase-sensitive (PhS)-optical coherence tomography
system is used to track/image the mechanical wave. The reconstructed transient
displacement of the mechanical wave in space and time demonstrates highly
efficient generation, thus offering great promise for non-contact, non-invasive
characterization of soft media, in general, and for elasticity measurements in
delicate soft tissues and organs in bio-medicine, in particular.
PMID- 27493277
TI - Front-line action to protect amphibian biodiversity.
PMID- 27493278
TI - Advances in veterinary practice.
PMID- 27493279
TI - Ethical question of the month - August 2016.
PMID- 27493280
TI - Epidemiology of toe tip necrosis syndrome (TTNS) of North American feedlot
cattle.
AB - Toe Tip Necrosis Syndrome (TTNS) is predominantly a hind limb lameness of feedlot
cattle that develops early in the feeding period. Retrospective analyses of
feedlot health records were conducted in order to describe the epidemiology of
the disease at the level of the individual animal, lot, and feedyard. Analysis of
1904 lots (cohorts of > 100 head) of cattle, from 48 feedyards, found that TTNS
occurred sporadically, but clustered by both lots and feedyards. Only 3.8% of
lots had >= 1 case of TTNS; however, 26.4% of these lots were associated with 1
feedyard. Analysis of 702 cases of TTNS found that the disease clusters early in
the feeding period; the mean (median; range) number of days on feed at death was
42.3 d (27.0 d; 4 to 302 d). The disease occurred in all months of the year and
affected calves, yearlings, steers, and heifers. It was equivocal as to whether
the source of the animals was associated with how quickly they died of TTNS in
the feedyard.
PMID- 27493281
TI - Erratum.
AB - [This corrects the article on p. 1025 in vol. 56, PMID: 26483575.].
PMID- 27493282
TI - Augmentation of arthrodesis in dogs using a free autogenous omental graft.
AB - A technique for using free autogenous omental grafting with arthrodesis in dogs
is described and radiographic osseous union and complications after surgery are
evaluated. This retrospective study matched body weight and procedure type for 8
cases of pancarpal arthrodesis, 4 cases of pantarsal arthrodesis, and 2 cases of
partial tarsal arthrodesis in dogs with omental and cancellous bone autograft
(OBG group) and with cancellous bone autograft alone (BG group). Radiographs were
reviewed 9 to 12 weeks after surgery to compare scores of radiographic osseous
union and it was found that the OBG group had higher scores than the BG group.
The BG group had significantly more major complications that required re
operation for implant removal or treatment of a deep infection compared to the
OBG group. Overall, free autogenous omental grafts may be used to augment
arthrodesis in dogs without significant morbidity and further investigation of
its use to reduce major complications and speed bone healing are warranted.
PMID- 27493284
TI - Post-operative complications associated with the Arthrex Canine Cranial Cruciate
Ligament Repair Anchor System in small- to medium-sized dogs: A retrospective
analysis (2009-2012).
AB - This study classified and determined the post-operative complication rate
associated with stabilization of cranial (CCL) ligament deficient stifles in
small- to medium-sized dogs with the Arthrex Canine Cranial Cruciate Ligament
Repair Anchor System (CCLRAS). Eighty-five medical records from 2009 to 2012 from
1 institution were evaluated. Complications were classified according to
previously proposed definitions for orthopedic studies in veterinary medicine.
Fifty-two owners were contacted by telephone at least 6 months after surgery and
given a questionnaire to classify complications related to the implant. A visual
analog scale was used to assess functionality and degree of pain. The overall
complication rate was 30.3% with an inflammation-infection rate of 5.4% and a
documented infection rate requiring implant removal of 1.8%. Owners reported full
or acceptable function in 96% of cases with an average functional score of 86.5.
Stabilization of CCL-deficient stifles in small- to medium-sized dogs with the
Arthrex Canine CCLRAS is reliable with acceptable complication rates.
PMID- 27493283
TI - Outcome and prognostic factors for dogs with a histological diagnosis of splenic
hematoma following splenectomy: 35 cases (2001-2013).
AB - Canine splenic hematoma can be indistinguishable from hemangiosarcoma on clinical
presentation and grossly at the time of surgery. However, hemangiosarcoma
represents an aggressive malignancy and a misdiagnosis of hematoma would forgo
indications for chemotherapy. This study describes a long-term follow-up of cases
with a histologic diagnosis of splenic hematoma following splenectomy to
determine if the clinical course of the disease corroborated the diagnosis.
Thirty-five dogs were evaluated to determine survival and prognostic associations
with signalment and clinical data. Overall median survival time was 647 days
(range: 0 to 3287 days). Statistically significant variables included a palpable
abdominal mass during physical examination, sub-clinical coagulopathy, and
metastasis. Four cases (11%) had reported evidence of metastasis at the time of
euthanasia; 1 case was histologically confirmed. Overall prognosis for splenic
hematoma appears excellent, as expected, but a small proportion of cases may have
an undiagnosed malignant component.
PMID- 27493285
TI - Long-term mechanical milking status of lacerated teat repaired surgically in
cattle: 67 cases (2003-2013).
AB - This study evaluated the long-term prognosis of return to normal mechanical
milking after reconstructive teat surgery and determined the factors that have an
impact on the outcome. A retrospective study of 67 dairy cows with teat
lacerations was performed. Milking status at discharge and at long-term follow-up
was adequate for 83% and 75% of the cows, respectively. No statistically
significant differences were detected between the long-term prognosis and the age
of the cow, the stage of lactation at presentation, or the configuration of the
laceration. Lacerations repaired more than 24 hours after the trauma were more
frequently associated with a negative outcome (P = 0.05). Mastitis was the most
frequent complication (n = 17) and had a statistically significant negative
impact on long-term prognosis (P = 0.02). Reconstructive surgery of lacerated
teat in dairy cows can help establish return to normal mechanical milking.
PMID- 27493286
TI - A cluster of trace-concentration methamphetamine identifications in racehorses
associated with a methamphetamine-contaminated horse trailer: A report and
analysis.
AB - Three low concentration methamphetamine "positive" tests were linked to use of a
methamphetamine-contaminated trailer to transport the affected horses. This
incident establishes methamphetamine as a human-use substance that can
inadvertently enter the environment of racing horses, resulting in urinary
methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for
methamphetamine in post-race urine is proposed.
PMID- 27493287
TI - A case of factor X deficiency in a Chihuahua dog.
AB - A juvenile Chihuahua dog developed hemoperitoneum after routine
ovariohysterectomy. She was managed with packed red blood cell and fresh frozen
plasma transfusions as well as an exploratory laparotomy to verify ligature
sites. No recurrence of hemorrhage occurred. Factor X deficiency was diagnosed
and confirmed with repeat analysis including during times of health.
PMID- 27493288
TI - Sialoendoscopy as a treatment for an obstructed mandibular salivary duct in a
horse.
AB - A 14-year-old Quarter Horse was examined for a draining tract of 8 months'
duration on the right mandible that was non-responsive to antibiotic therapy and
surgical therapy. Further investigation and subsequent treatment with
sialoendoscopy and ultrasonography were performed to relieve an obstruction of
plant awns in the mandibular salivary duct.
PMID- 27493289
TI - Ventral rhinotomy in a pet rabbit (Oryctolagus cuniculus) with an odontogenic
abscess and sub-obstructive rhinitis.
AB - A rabbit was presented for severe dyspnea and was diagnosed with an odontogenic
abscess obstructing the rostral nasopharynx using CT scan and oral endoscopy. The
offending tooth was extracted intraorally, but due to persistent dyspnea, an
endoscopic-guided ventral rhinotomy was performed. The dyspnea subsequently
resolved, but the rabbit died 5 weeks later from a seemingly unrelated cause.
PMID- 27493290
TI - Non-invasive magnetic resonance imaging diagnosis of presumed intermedioradial
carpal bone avascular necrosis in the dog.
AB - A 5-year-old, spayed female Weimaraner dog was evaluated for progressive left
forelimb lameness localized to the carpus. Magnetic resonance imaging (MRI) was
used to arrive at a presumptive diagnosis of intermedioradial carpal (IRC) bone
fracture with avascular necrosis (AVN). To the authors' knowledge, this is the
first report of naturally occurring AVN of the canine IRC diagnosed using MRI.
PMID- 27493291
TI - Pain in human and non-human animals caused by electricity.
PMID- 27493292
TI - Lessons for the first year in "practice".
PMID- 27493293
TI - Clinical practice is not mandatory.
PMID- 27493294
TI - Avoidance and enhancing screen-based communication.
PMID- 27493295
TI - INHALED AEROSOL DOSIMETRY: SOME CURRENT RESEARCH NEEDS.
AB - After the presentation of 60 papers at the conference "Advancing Aerosol
Dosimetry Research" (October 24-25, 2014 in Irvine, CA, USA), attendees submitted
written descriptions of needed research. About 40 research needs were submitted.
The suggestions fell into six broad categories: 1) Access to detailed anatomic
data; 2) Access to subject-specific aerosol deposition datasets; 3) Improving
current inhaled aerosol deposition models; 4) Some current experimental data
needs and hot topics; 5) Linking exposure and deposition modeling to health
endpoints; and 6) Developing guidelines for appropriate validation of dosimetry
and risk assessment models. Summaries of suggestions are provided here as an
update on research needs related to inhaled aerosol dosimetry modeling. Taken
together, the recommendations support the overarching need for increased
collaborations between dose modelers and those that use the models for risk
assessments, aerosol medicine applications, design of toxicology experiments, and
extrapolation across species. This paper is only a snapshot in time of perceived
research needs from the conference attendees; it does not carry the approval of
any agency or other group that plans research priorities or that funds research.
PMID- 27493296
TI - Total and regional deposition of inhaled aerosols in supine healthy subjects and
subjects with mild-to-moderate COPD.
AB - Despite substantial development of sophisticated subject-specific computational
models of aerosol transport and deposition in human lungs, experimental
validation of predictions from these new models is sparse. We collected aerosol
retention and exhalation profiles in seven healthy volunteers and six subjects
with mild-to-moderate COPD (FEV1 = 50-80%predicted) in the supine posture. Total
deposition was measured during continuous breathing of 1 and 2.9 MUm-diameter
particles (tidal volume of 1 L, flow rate of 0.3 L/s and 0.75 L/s). Bolus
inhalations of 1 MUm particles were performed to penetration volumes of 200, 500
and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and
mode shift (MS) were calculated from these data. There was no significant
difference in total deposition between healthy subjects and those with COPD.
Total deposition increased with increasing particle size and also with increasing
flow rate. Similarly, there was no significant difference in aerosol bolus
deposition between subject groups. Yet, the rate of increase in dispersion and of
decrease in MS with increasing penetration volume was higher in subjects with
COPD than in healthy volunteers (H: 0.798 +/- 0.205 vs. 0.527 +/- 0.122 mL/mL,
p=0.01; MS: -0.271+/-0.129 vs. -0.145 +/- 0.076 mL/mL, p=0.05) indicating larger
ventilation inhomogeneities (based on H) and increased flow sequencing (based on
MS) in the COPD than in the healthy group. In conclusion, in the supine posture,
deposition appears to lack sensitivity for assessing the effect of lung
morphology and/or ventilation distribution alteration induced by mild-to-moderate
lung disease on the fate of inhaled aerosols. However, other parameters such as
aerosol bolus dispersion and mode shift may be more sensitive parameters for
evaluating models of lungs with moderate disease.
PMID- 27493297
TI - Characterization of an S-nitroso-N-acetylpenicillamine-based nitric oxide
releasing polymer from a translational perspective.
AB - Due to the role of nitric oxide (NO) in regulating a variety of biological
functions in humans, numerous studies on different NO releasing/generating
materials have been published over the past two decades. Although NO has been
demonstrated to be a strong antimicrobial and potent antithrombotic agent, NO
releasing (NOrel) polymers have not reached the clinical setting. While
increasing the concentration of the NO donor in the polymer is a common method to
prolong the NO-release, this should not be at the cost of mechanical strength or
biocompatibility of the original material. In this work, it was shown that the
incorporation of S-nitroso-penicillamine (SNAP), an NO donor molecule, into Elast
eon E2As (a copolymer of mixed soft segments of polydimethylsiloxane and
poly(hexamethylene oxide)), does not adversely impact the physical and biological
attributes of the base polymer. Incorporating 10 wt % of SNAP into E2As reduces
the ultimate tensile strength by only 20%. The inclusion of SNAP did not
significantly affect the surface chemistry or roughness of E2As polymer.
Ultraviolet radiation, ethylene oxide, and hydrogen peroxide vapor sterilization
techniques retained approximately 90% of the active SNAP content, where
sterilization of these materials did not affect the NO-release profile over an 18
day period. Furthermore, these NOrel materials were shown to be biocompatible
with the host tissues as observed through hemocompatibility and cytotoxicity
analysis. In addition, the stability of SNAP in E2As was studied under a variety
of storage conditions, as they pertain to translational potential of these
materials. SNAP-incorporated E2As stored at room temperature for over 6 months
retained 87% of its initial SNAP content. Stored and fresh films exhibited
similar NO release kinetics over an 18 day period. Combined, the results from
this study suggest that SNAP-doped E2As polymer is suitable for commercial
biomedical applications due to the reported physical and biological
characteristics that are important for commercial and clinical success.
PMID- 27493299
TI - A new horizon for the Sudanese Journal of Paediatrics.
PMID- 27493298
TI - Financial Transfers to Husbands' and Wives' Elderly Mothers in Mexico: Do Couples
Exhibit Preferential Treatment by Lineage?
AB - The aim of this study was to contrast the likelihood that a husband's elderly
mother receives financial assistance from a couple with that of a wife's mother.
Prior U.S.-based research has documented a strong bias toward transfers to wives'
parents. The authors aimed to extend this literature to Mexico, where financial
help from adult children is a critical source of support for a rapidly aging
population lacking institutional assistance. The authors' approach to modeling
competition between mothers accounted for the nature of their need. The results
demonstrate that among mothers of similar financial need, a husband's mother is
twice as likely to receive financial assistance as a wife's mother. In contrast,
when faced with personal care needs, a wife's mother is disproportionately
favored. These results reflect gender differences in Mexican adult children's
responsibility for family members' financial and physical well-being. The
findings uncover new complexity in the patterns by which couples transfer money
to parents of different lineage.
PMID- 27493300
TI - Evaluation of Science.
AB - Scientific achievement by publishing a scientific manuscript in a peer reviewed
biomedical journal is an important ingredient of research along with a career
enhancing advantages and significant amount of personal satisfaction. The road to
evaluate science (research, scientific publications) among scientists often seems
complicated. Scientist's career is generally summarized by the number of
publications / citations, teaching the undergraduate, graduate and post-doctoral
students, writing or reviewing grants and papers, preparing for and organizing
meetings, participating in collaborations and conferences, advising colleagues,
and serving on editorial boards of scientific journals. Scientists have been
sizing up their colleagues since science began. Scientometricians have invented a
wide variety of algorithms called science metrics to evaluate science. Many of
the science metrics are even unknown to the everyday scientist. Unfortunately,
there is no all-in-one metric. Each of them has its own strength, limitation and
scope. Some of them are mistakenly applied to evaluate individuals, and each is
surrounded by a cloud of variants designed to help them apply across different
scientific fields or different career stages [1]. A suitable indicator should be
chosen by considering the purpose of the evaluation, and how the results will be
used. Scientific Evaluation assists us in: computing the research performance,
comparison with peers, forecasting the growth, identifying the excellence in
research, citation ranking, finding the influence of research, measuring the
productivity, making policy decisions, securing funds for research and spotting
trends. Key concepts in science metrics are output and impact. Evaluation of
science is traditionally expressed in terms of citation counts. Although most of
the science metrics are based on citation counts but two most commonly used are
impact factor [2] and h-index [3].
PMID- 27493301
TI - The role of the health system in the prevention of hearing loss among children in
Sub-Saharan Africa.
AB - Around 1.2 million children living in Sub-Saharan Africa have a hearing
impairment (HI) or hearing loss (HL). Limited attention and scarce resources
dedicated to this condition means that such children often receive no management
for their problem. This has substantial negative effects on their development,
and ultimately results in poverty. Half of the number of cases of HI in such
countries results from preventable causes. Formulation of effective prevention
strategies to address the causes requires an understanding of the factors that
lead to the causes of HI in Sub-Saharan Africa. A number of preventable causes
were shown to significantly contribute to the prevalence of HI. The most
significant causes include perinatal problems, middle ear problems, infective
diseases, and ototoxic drugs. These causes persist because there are few
effective prevention strategies in place, and those which exist are poorly
implemented. There is little public and health care worker awareness about HL and
its prevention. Few resources are allocated to the prevention of HL, meaning that
these issues are not addressed. Evidence have shown that current failings in the
prevention of HI from such causes include widespread limited resources,
inadequate staff training, and absent or ineffectual prevention guidelines. The
burden of HL has been shown to be significantly reduced through effective
prevention strategies, both in the developed and developing world, justifying the
need for increased attention and more resources in Sub-Saharan Africa.
PMID- 27493302
TI - Recognition and diagnostic approach to acute metabolic disorders in the neonatal
period.
AB - Inborn errors of metabolism (IEM) constitute a group of inherited disorders that
cause significant neonatal morbidity and mortality. This diverse group of
diseases present with different clinical manifestations that make the diagnosis a
real challenge. Early detection and appropriate investigations prevent
complications and save lives. The aim of this review is to enable general
paediatricians to clinically recognize IEM and plan relevant investigations at
the appropriate time in a cost-effective manner, especially in countries where
resources are limited.
PMID- 27493303
TI - Recent intrauterine growth parameters of term Sudanese neonates in Khartoum
compared to the findings three decades earlier.
AB - The objective of this paper was to present anthropometric measurements of term
Sudanese neonates which will reflect intrauterine growth. Secondly, to compare
such parameters with that of a previous study done about three decades ago to
show if there is any secular changes. Normal term neonates born to healthy
mothers between the period of October 2010 to January 2011 at Khartoum Teaching
Hospital were included in the study. There were certain criteria for inclusion
and exclusion of the newborns and their mothers. Measurements of birth weight,
crown-heel length and head circumferences were done in the first twenty four
hours after birth. Statistical test of the difference between the means was used
to show any significant difference. The means of birth weight, crown-heel length
and head circumference for both sexes against gestational age were obtained.
Comparing this study with the previous one showed no statistical significant
difference for both sexes regarding the birth weight, crown-heel length but there
is some difference between males head circumference. There is no evidence of
upward secular trend regarding the intrauterine parameters.
PMID- 27493304
TI - Pathologic causes of liver disease in Sudanese children: Results of 450 liver
needle biopsies at a single children hospital.
AB - The pathologic diagnoses of percutaneous 450 liver biopsies performed at the
Gastroenterology Unit, Gaafar Ibnoof Specialized Children Hospital, Khartoum,
Sudan during a five-year period (2005 to 2010) were reviewed. The cohort
consisted of children aged between 1 month and 15 years, of whom 42% were less
than 1 year of age. The male to female ratio was 1.4:1. The most common
histological diagnosis was liver cirrhosis (26%), where no specific cause could
be found, followed by neonatal hepatitis (20%), fatty liver (12%), billary
atresia (10%), chronic hepatitis (8%), metabolic liver disease (6%), progressive
intrahepatic cholestasis (5.5%), non-specific pathological changes (4.4%) and
hepatocellular carcinoma in (4%). In conclusion, liver biopsy is a useful and
practical tool for the appropriate diagnosis of pediatric liver diseases.
Hepatocellular carcinoma has significantly higher prevalence in our pediatrics
population.
PMID- 27493305
TI - Sanjad-Sakati Syndrome in Sudanese children.
AB - We report on the first 4 cases (3 girls and one boy belonging to 4 families) of
Sanjad-Sakati syndrome from Sudan. They presented within the first 2 months of
life with repeated hypocalcaemic convulsions, severe growth retardation and
dysmorphic features. They all had low parathyroid hormone levels. All patients
came from consanguineous families who are of Arab descent, and 8 of their
siblings had similar condition and died without being diagnosed.
PMID- 27493306
TI - Acute phase reactants in Sudanese children with severe protein-energy
malnutrition.
AB - The pre-dietary rehabilitation levels of acute phase proteins (APP) namely, alpha
1-antitrypsin (AAT), orosomucoid (ORO), haptoglobin (HAP), fibrinogen (FIB) and C
reactive protein (CRP) in the plasma of Sudanese children with severe protein
energy malnutrition (PEM) were compared with those of normal controls, and with
the levels after dietary rehabilitation. Eighty one children were included in the
study; 49 with severe PEM (23 with marasmus, 17 with marasmic-kwashiorkor and 9
with kwashiorkor), 13 with tuberculosis (TB) and 19 healthy children as controls.
The study showed a high incidence of infections, especially acute respiratory
infection (ARI), diarrhoeal diseases and intestinal parasites in the malnourished
children. The mean plasma level of albumin was significantly lower in the
malnourished children compared to controls (P<0.001), with kwashiorkor children
showing the lowest mean level. This hypoalbuminaemia was significantly associated
with the presence of ARI and intestinal parasites. The mean plasma levels of the
APP, except FIB, were significantly higher in malnourished children than in
controls, with higher levels associated with ARI and the presence of fever.
Malnourished children with TB had significantly higher mean levels of the APP
(AAT, HAP, FIB, CRP) compared to those without TB. The mean levels of HAP and AAT
were significantly lower in the presence of diarrhoea, suggesting their loss in
the stool. The mean levels of the APP after two weeks dietary rehabilitation and
antimicrobial treatment showed a significant drop in only two of the APP, namely
CRP, ORO, while FIB showed a significant rise.
PMID- 27493307
TI - Classic ataxia-telangiectasia in a Sudanese boy: Case report and review of the
literature.
AB - Ataxia-telangiectasia (A-T) is a rare hereditary neurodegenerative disorder.
Ataxia and telangiectasias are the hallmarks of the disease. A spectrum of
manifestations may be seen in one family. There is no gold standard diagnostic
test and diagnosis relies on clinical evaluation, exclusion of similar
conditions, and supportive laboratory tests. More than 99% of individuals with
classic A-T have mutations in ATM, the only gene known to be associated with
ataxia-telangiectasia. We report a 28-months-old Sudanese boy who was presented
with unsteady gait, frequent falls and telangectasias of the eyes. He also has
had frequent episodes of respiratory tract infections.
PMID- 27493308
TI - Tyrosinemia Typel: A case report.
AB - Tyrosinemia type 1 is an inherited metabolic disorder attributable to deficiency
of fumarylacetoacetate hydrolase enzyme. Here we report an eight month-old male
Saudi infant who presented with jaundice, fever, and disturbed level of
consciousness accompanied by abdominal distension, hepatomegaly and ascites with
features suggestive of rickets. The diagnosis of tyrosinemia typ 1was confirmed
based on clinical and biochemical findings.
PMID- 27493309
TI - Ascaris Lumbricoides in a 13-year-old child.
PMID- 27493310
TI - Pioneers of Paediatrics in Sudan: Professor Mahmoud Mohamed Hassan: FRCP
(Edinburgh), FRCP (Glasgow), FAAP.
PMID- 27493311
TI - Guidelines to Contributors.
AB - To address the task of the expansion of the Sudanese Journal of Paediatrics (SJP)
to encompass the scientific work dealing with child health locally and abroad, it
will be the purpose of the Editorial Board of SJP to encourage authors to submit
high-quality papers for the refereed publication and to make a more varied source
of material to our readers. "Guidelines to contributors "are published to help
the authors to present their data in accordance with the currently accepted
uniform style for submitted manuscripts. It is based on the recommendations of
the International Committee of Medical Journal Editors [1] with minor
modifications to suit the local facilities in developing countries.
PMID- 27493312
TI - Commitment to the wellbeing of children worldwide.
PMID- 27493313
TI - Treatment strategies for acute metabolic disorders in neonates.
AB - Acute metabolic emergencies in neonates represent a challenge to the medical and
nursing staff. If not treated optimally, these disorders are associated with poor
outcome. Early diagnosis, supportive therapy and specific measures addressing the
derranged metabolic process are the gold standards for favorable results. This
review highlights treatment strategies for Inborn Errors of Metabolism (IEM)
presenting in the neonatal period.
PMID- 27493314
TI - The effect of qat chewing and other factors on breast-feeding and child survival
in a Yemeni society.
AB - In a survey conducted in Dammar, Republic of Yemen, 755 mothers were interviewed
to investigate the patterns and factors affecting childhood feeding practices. It
was found that full breast-feeding rate (41.8%) and timely introduction of
complementary feeding rate (57.4%) were low, bottle-feeding rate (25.1%) was high
and timely first suckling rate was zero. It was also found that the more educated
and older mothers tended to wean their children earlier than illiterate and
younger mothers. A significant association between regular frequent qat chewing
and history of child death was observed. The implications of these findings were
discussed.
PMID- 27493315
TI - Donkey milk-based formula: A substitute for patients with cow's milk protein
allergy.
AB - Cow's milk protein allergy affects 2-7% of children using cow's milk formulae.
Fifty to eighty percent of them develop allergy to other food items and
substitutes. On the search for a safe and affordable substitute, we reviewed the
composition of milks of the domestic mammals in close contact with man. Milk
constituents studied included fat, protein, lactose, minerals, water, pH,
specific gravity and caloric value. Compared to others, donkey milk was found to
be closest to breast milk when the amount of 16ml of sunflower is added to one
liter of this milk. To our knowledge, no allergy to donkey milk has been reported
yet.
PMID- 27493316
TI - Characteristics associated with severe pneumonia in under-five children admitted
to emergency units of two teaching hospitals in Khartoum, Sudan.
AB - Pneumonia, defined as infection of lung parenchyma, is associated with severe
complications especially in the very young and old patients. It is the world's
leading cause of childhood mortality. The World Health Organization (WHO)
classification and guidelines are commonly used in Sudan in the diagnosis and
management of pneumonia patients. A group of 224 patients at Gaafar Ibn Oaf
Children's Hospital and Omdurman Children's Hospital were assessed and managed
for severe presentation of pneumonia. The data collected showed that most of the
patients were of low socioeconomic class families. The vast majority (99%) of
patients had chronic exposure to tobacco smoke at home. Female patients (52.7%)
were more than males, with 42% of the presenting patients in the less than 12
months age group. Pneumonia is a dangerous childhood menace that is associated
with severe presentations. Public health community outreach programs should be
put in place to raise awareness. The case fatality rate during the study period
was 4%.
PMID- 27493317
TI - Infection and immunoglobulin levels in Sudanese children with severe protein
energy malnutrition.
AB - A hospital-based case control study was carried out to determine the pattern of
infections and immunoblobulin levels in Sudanese children with severe protein
energy malnutrition (PEM). The pre-dietary rehabilitation levels of the three
major immunoglobulins (IgG, IgA and IgM) were compared with those of normal
controls, and with the levels after dietary rehabilitation. Eighty one children
were included in the study: 49 with severe PEM (23 with marasmus, 17 with
marasmic - kwashiorkor and 9 with kwashiorkor), 13 with tuberculosis and 19
healthy children as controls. The study showed high incidence of infections,
especially pneumonia and gastrointestinal infections in the malnourished
children. Of special concern was the high incidence of urinary tract infection:
13 (26.5%) had significant pyuria and 9 of them had positive urine cultures,
mainly Escherichia coli. Eight of the malnourished children also had pulmonary
TB, and the ESR and Mantoux tests were not helpful in the diagnosis. The Mantoux
test was negative in 88.8% of the malnourished group compared to 62.5% in those
malnourished with TB. The malnourished groups had significantly higher plasma
levels of the 3 immunoglobulins. While the maramic group attained significantly
higher levels of IgG and IgA compared to the marasmic -kwashiorkor and
kwashiorkor groups, the 3 groups of PEM showed a uniformly higher level of the
IgM. After 2 weeks of rehabilitation, the levels of the 3 immunoglobulins showed
no significant changes, except for the IgA which significantly decreased in all
malnourished and the oedematous groups, and the IgM which increased significantly
in the oedematous group.
PMID- 27493318
TI - Button battery induced traumatic tracheoesophageal fistula: Case report and
review of literature.
AB - Although accidental ingestions by children of various household chemicals and
medicines are well described and the treatment is supported by protocols and
hotlines, the ingestion of button batteries is less publicized, and the dangers
are less understood by both parents and health care providers. We describe the
case of a three-year-old girl, who presented to hospital with respiratory
distress, cough, and fever; three weeks after the ingestion of a button battery.
Endoscopic examination revealed impacted 20 mm disc battery, which was removed,
and a tracheoesophageal fistula (TOF) in the upper third of the oesophagus
associated with severe oesophagitis, and oesophageal ulcers. There was also
evidence of oesophageal fungal infection, and severe hyperemic pan-gastritis and
duodenitis. Parents were counseled and conservative management advised, but they
opted for surgical repair of the TOF. The operation was done and the child
survived, but she ended up with a tracheal stricture and recurrent chest
infections. In conclusion, oesophageal button battery impaction places the
patient at high risk for tracheoesophageal fistula. The key to successful therapy
is prompt diagnosis and removal, which saves life and decreases morbidity.
Because of the complications associated with this condition, patients should be
managed at an institution with skilled personnel and facilities for advanced life
support.
PMID- 27493319
TI - Dicephalus tribrachius conjoined twins: Case report and review of literature.
AB - Conjoined twins is a phenomenon believed to be caused by either delayed splitting
of the fertilized ovum or fusion of the embryonic stem cells. Disorganization of
mutant genes is believed to be a cause in some cases. We report a case of
stillborn dicephalus tribrachius female conjoined twins with features that are
not reported previously in the literature with a single umbilical artery and two
urinary bladders. The cause of intrauterine death in this case was probably multi
factorial i.e. severe anemia in the mother, congestive heart failure,
complications of obstructed labor and multiple skull fractures.
PMID- 27493320
TI - Zellweger syndrome: A cause of neonatal hypotonia and seizures.
AB - Zellweger syndrome, a paradigm of human peroxisomal disorders is characterized by
dysmorphic features, hypotonia, severe neuro-developmental delay, hepatomegaly,
renal cysts, sensorineural deafness and retinal dysfunction. This is a case
report of a baby boy born with facial dysmorphism, profound hypotonia, seizures,
and hepatomegaly. The diagnosis was not evident initially but only later when he
presented with obstructive jaundiced and renal cysts. He died at the age of seven
months. Biochemical studies revealed elevation of very long chain fatty acids and
phytanic acid consistent with a peroxisomal disorder. The recognition of this
syndrome is important since it is a fatal hereditary disease. Zellweger syndrome
should be included in the differential diagnosis of infantile hypotonia and
dysmorphism.
PMID- 27493321
TI - Walker-Warburg Syndrome: A Case with multiple uncommon features.
AB - Walker-Warburg syndrome (WWS) is a rare and lethal autosomal recessive disorder,
caused by defective glycosylation of alpha-dystroglycan that is important for
muscle integrity and neuronal migration. Mutations in six genes involved in the
glycosylation of alpha-dystroglycan (POMT1, POMT2, POMGNT1, FCMD, FKRP and LARGE)
have been identified in WWS patients, and others remain under study. Prenatal
diagnosis may be possible by means of prenatal ultrasonography, or magnetic
resonance imaging. We report a patient demonstrating the typical clinical
features of lissencephaly, congenital muscular dystrophy and ocular
abnormalities, in addition to other features including hydrocephalus, occipital
encephalocele, agenesis of the corpus collosum, microphthalmia, ventricular
septal defect, and rocker bottom feet deformity.
PMID- 27493322
TI - Guidelines to Contributors.
AB - To address the task of the expansion of the Sudanese Journal of Paediatrics (SJP)
to encompass the scientific work dealing with child health locally and abroad, it
will be the purpose of the Editorial Board of SJP to encourage authors to submit
high-quality papers for the refereed publication and to make a more varied source
of material to our readers. "Guidelines to contributors "are published to help
the authors to present their data in accordance with the currently accepted
uniform style for submitted manuscripts. It is based on the recommendations of
the International Committee of Medical Journal Editors [1] with minor
modifications to suit the local facilities in developing countries.
PMID- 27493323
TI - Changing an old therapy of a historic human infection: Malaria.
PMID- 27493324
TI - Time to switch from quinine.
PMID- 27493325
TI - Drug-resistant malaria in Sudan: A review of evidence and scenarios for the
future.
AB - Resistance of falciparum malaria to chloroquine (CQ) has gradually emerged in the
late 1970s, reaching unacceptably high proportions over the following three
decades of use as frst line treatment in Sudan. By 2004-2006 CQ was replaced by
artemisinin-based combination treatment (ACTs), with combination of sulfadoxine
pyrimethamine (SP) and artesunate (AS) deployed as frst-line drug against
falciparum malaria. The present review follows the evolution of CQ resistance in
Sudan and the available evidence on the response to the present frst-line drugs.
The fndings in Sudan are analyzed in view of developments in other African
countries and at the global level, with the hope of elucidating possible
scenarios for the course of events in the Sudan. Northern Sudan has been one of
the areas where signals indicating the emergence of drug resistant malaria
parasites have frst originated in Africa. The pattern of low endemicity and low
population immunity to malaria, together with massive deployment and improper use
of anti-malarial drugs created the ideal environment for creation of anti
malarial drug resistance. Such an environment existed in certain areas in South
East Asia that had historically been the epicenter from which falciparum malaria
parasites resistant to pyrimethamine and chloroquine have spread to the rest of
the world. The alarming recent reports about the emergence of artemisinin (ART)
resistance in South East Asia have lead WHO to take specifc measures for
prevention, early detection and containment of drug resistance. What could be
applicable in Sudan in these measures is discussed here.
PMID- 27493326
TI - Neonatal follow-up program: Where do we stand?
AB - Neonatal follow-up program (NFP) is becoming the corner stone of standard, high
quality care provided to newborns at risk of future neuorodevelopmental delay.
Most of the recognized neonatal intensive care units in the developed countries
are adopting NFP as part of their mandatory care for the best long term outcome
of high risk infants, especially very low birth weight (VLBW) infants.
Unfortunately, in the developing and in underdeveloped countries, such early
detection and intervention programs are rarely existing, mainly because of the
lack of awareness of and exposure to such programs in spite of the increasing
numbers of surviving sick newborns due to advancement in neonatal care in these
countries. This is a review article to explore the Neonatal follow-up programs
looking at historical development, benefts and aims, and standard requirements
for successful program development that can be adopted in our countries. In
conclusion, proper Neonatal follow-up programs are needed to improve neonatal
outcome. Therefore all professionals working in the feld of neonatal care in
developing countries should cooperate to create such programs for early detection
and hence early intervention for any adverse long term outcome in high-risk
newborn infants.
PMID- 27493327
TI - Childhood immune thrombocytopenia: Clinical presentation and management.
AB - Immune thrombocytopenia (ITP) is an acquired hematological disorder that is
developed secondary to the production of auto-antibodies against platelets
leading to isolated thrombocytopenia, in the absence of other causes of
thrombocytopenia such as drugs, infections, malignancy, or other autoimmune
diseases [1-6]. ITP commonly affects children between one and seven years of age.
Severe life threatening bleeding is rare (0.2-0.9%) [7-12]. Childhood primary ITP
usually runs a benign, self-limiting course, with or without treatment. Complete
remission occurs within six months from diagnosis, commonly within 6-12 weeks, in
the majority of children with the diagnosis of ITP. However, 20-30% of children
will continue to have persistent low platelets count with bleeding symptoms
beyond six months from diagnosis [4, 12-18]. The diagnosis of ITP in children is
essentially one of exclusion. The child is usually one to seven years old,
develops skin bruises, petechiae, or mucosal bleeding, who is otherwise healthy
and having no lymphadenopathy or organomegally. Full blood count reveals isolated
thrombocytopenia with normal hemoglobin (Hb) level, white blood count (WBC) and
normal peripheral blood smear. Initial management options for newly diagnosed
childhood ITP include; observation only, the use of intravenous immunoglobulin
(IVIG), steroids, anti-D immunoglobulin, each alone or in combination [6, 19.]
Children who develop chronic ITP may benefit from splenectomy [19, 20-24].
Rituximab, a chimeric monoclonal antibody (anti-CD20), may lead to complete
remission, and defers the need for splenectomy [25-27]. Recently, the
thrombopoietin (TPO) agonists (Romiplostim and Eltrombopag) produced very good
response in adult and pediatric patients with severe chronic ITP [28-30].
PMID- 27493328
TI - Morbidity and mortality amongst infants of diabetic mothers admitted into Soba
university hospital, Khartoum, Sudan.
AB - The prevalence of diabetes during pregnancy is increasing and this is associated
with an increased risk of complications in both mother and fetus. The aim of this
research is to study the neonatal complications of maternal diabetes. This was a
prospective observational study that was conducted in Soba university hospital
between September 2010 and March 2011. All infants born to diabetic mothers
during the study period were admitted to the neonatal care unit for evaluation.
Data on sex, gestational age, and birth weight, mode of delivery, complications,
investigations, birth injury, and length of hospital stay were recorded. Maternal
data were retrieved from records. Data was analyzed using Minitab 15. A total of
50 infants of diabetic mothers (IDMs) were included in the study. Thirty infants
(60%) were females and 20 (40%) were males. Forty two (84%) of the neonates were
born by caesarian section, only 7(14%) were born by spontaneous vaginal delivery.
Birth injury was observed in 4% of them. The mean gestational age was 37.2+/
2.051 weeks. The median birth weight was 3.5 kg. 14 (28%) of the babies were
macrosomic, and 17 (34%) were large for gestational age (LGA). Congenital
anomalies were found in 3 (6%), hypoglycemia in 6 (12%), hyperbillirubinaemia in
10 (20%), hypocalcaemia and hypomagnesaemia each occurred in 2%, transient
tachypnea of the newborn occurred in 5 (10%) of the neonates and respiratory
distress syndrome in 2%. Cardiomyopathy occurred in 2% and mortality was 4%. We
concluded that macrosomia, LGA, and hyperbillirubinaemia were the commonest
complications in IDMs, maternal glycaemic control was found to have a significant
effect on a number of outcomes.
PMID- 27493329
TI - Rickets and osteomalacia in Saudi children and adolescents attending endocrine
clinic, Riyadh, Saudi Arabia.
AB - This is a retrospective study in which we report our clinical experience during
the period from January 1990 to December 2009, from a paediatric endocrine clinic
at King Khalid University Hospital (KKUH), Riyadh, Saudi Arabia. The diagnosis of
rickets and oestomalacia was based on clinical, biochemical and radiological
data. Eighty-one (34 males and 47 females) children and adolescents with rickets
or osteomalacia aged 2 to 18 years (mean; 9.5 years) were evaluated. The
commonest causes were nutritional; either low Vitamin D or calcium, or both. In
58 (71.60%) patients, eight patients (9.87%) were due to chronic use of
anticonvulsant medications, while five (6.17%) patients were diagnosed to have
celiac disease. Non-specific symptoms, such as bone pain and fatigue were the
most common presenting symptoms which may indicate that other cases were possibly
missed. Lack of direct sun exposure and malnutritional practices were evident.
Several genetically inherited disorders were diagnosed; including;
hypophosphataemic rickets in three (3.70%), vitamin D-dependent-rickets type 2 in
five (6.17%) and pseudohypo-hyperparathyroidism in one (1.23%) child. Rickets was
secondary to chronic renal failure in only one patient (1.23%). In conclusion, a
diversity of disorders caused rickets or osteomalacia in our series.
Paediatricians should be familiar with such different types and able to
differentiate them from disorders mimicking rickets. rickets, such as
hypophosphatasia, and metaphyseal dysplasias. An active plan should be put in
place to prevent rickets and osteomalacia among young age groups.
PMID- 27493330
TI - Prescription writing quality in paediatric teaching hospitals in Khartoum.
AB - This study was conducted to analyze the quality of prescription writing of
doctors in outpatient departments of paediatric teaching hospitals in Khartoum.
This study is a descriptive cross- sectional, prospective, hospital based study.
Nine hundred paediatric prescriptions collected from three paediatric teaching
hospitals were analyzed. Three hundred prescriptions were also collected from
doctors after giving them a case scenario for which they were asked to write
appropriate prescriptions. These prescriptions were also analyzed for their
completeness. Inadequate writing of the sex of the patient, weight, and height
were notable regarding patient information. Generic names, concentration of the
drug and treatment duration of the drug were poorly mentioned. Designation and
identification of the prescriber were not adequately mentioned. In the case
scenario 65.3 % of doctors wrote low quality prescriptions. Registrars wrote
better prescriptions than medical officers who wrote better than house officers.
Outpatient department prescriptions were unsatisfactory due to lack of necessary
information for the ideal prescription. Also doctors, in response to case
scenario, wrote low quality prescriptions. To improve prescription writing
skills, we suggest that hospitals should provide standard prescription forms that
contain the necessary fields for identification of both, patient and doctor.
PMID- 27493331
TI - Cardiac manifestations of sickle cell anaemia in Sudanese children.
AB - Sickle cell anaemia (SCA) is one of the commonest chronic hemolytic anaemias in
the Sudan; it is a disease with high mortality and morbidity. This study was
conducted aiming to observe the clinical pattern of cardiac abnormalities in
children with sickle cell anaemia, and to assess the relationship between the
cardiac abnormalities and the severity of the disease. The study was conducted in
sickle cell disease clinic at Khartoum Children Emergency Hospital. The study
group consisted of 289 patients with sickle cell anaemia, age range from 6 months
to 18 years. Data were collected using a questionnaire which include full
history, clinical examination findings, chest x-rays, and Electro-cardiography.
Tachycardia, systolic murmurs, and cardiomegaly were detected in 28%, 61%, and
54% of patients with SCA respectively. Left ventricular dilatation was observed
in 51% of the study group, while right ventricular dilatation was observed in 22%
of the patients. Left and right atrial dilatations were observed in 16% and 6% of
the patients respectively. Contractility, ejection fraction (EF) were found
almost always normal in all study subjects. Chamber dilatations were not
associated with any abnormality in Left ventricular functions. Hemglobin (Hb)
levels correlated negatively with cardiomegaly. Left Ventricular End Diastolic
Dimension (LVEDD) correlates negatively with Hb levels and positively with the
severity index. Only four patients (1%) had abnormal valves. In conclusion,
cardiac abnormalities in patients with SCA correlate with the age of the patients
and the severity of the disease.
PMID- 27493332
TI - Short stature in children: Pattern and frequency in a pediatric clinic, Riyadh,
Saudi Arabia.
AB - Longitudinal growth assessment is essential in child care. Short stature can be
promptly recognized only with accurate measurements of growth and critical
analysis of growth data. The objective of this study was to determine the pattern
of short stature among patients referred to an endocrine pediatric clinic, King
Khalid University Hospital (KKUH), Riyadh, Saudi Arabia and to ascertain the
aetiological profile of short stature. This is a retrospective review of patients
referred to a pediatric endocrine clinic with short stature during the period
January 1990 and December 2009. After a proper detailed medical history, growth
analysis and physical examination, followed by a radiological (bone age) and
laboratory screening (complete blood count and thyroid function). Growth hormone
stimulation tests were performed when indicated. Magnetic resonance imaging (MRI)
of the pituitary was performed when necessary. As well, celiac screening and
small bowel biopsy were performed when appropriate. During the period under
review, hundred and ten patients were evaluated for short stature. Their age
ranged from 2 years and six months to 4 years. The male to female ratio was
1.3:1. The commonest etiology was genetic short stature found in 57 (51.8%)
patients, while in the other 53 (48.2%) patients, variable endocrine and
nutritional causes were noted. Short stature was a common referral. A wide
variety of etiological diagnosis was noticed with genetic short stature being the
commonest. A wide variety of endocrine causes were evident, with growth hormone
deficiency, as a results of different etiologies, being the commonest.
PMID- 27493333
TI - Incomplete Kawasaki disease: The usefulness of BCG reactivation as a diagnostic
tool.
AB - Kawasaki disease (KD) is an extremely rare condition in infants younger than 3
months old. Cardiovascular complications are unfortunately most common in young
infants and it is in this age group, incomplete Kawasaki disease (IKD) is more
frequently reported. Because IKD is a diagnostic dilemma, any sign that could
help early diagnosis, such as BCG reactivation is useful. Here we report on an
infant less than 3 months old with IKD wherein, BCG reactivation helped us in
making the diagnosis. In this article, we highlight the usefulness of this sign
for early diagnosis of IKD, especially in countries where BCG vaccination is
still part of the immunization schedule.
PMID- 27493334
TI - Breast carcinoma in a boy with metastatic axillary lymph nodes.
AB - The purpose of this report is to highlight the clinicopathological features,
diagnosis, management and prognosis of rare childhood breast cancer. We herein
report a case of slowly growing, locally advanced secretory carcinoma of the
breast in an 11-year-old boy with metastatic axillary lymph nodes, 12 of them
were totally replaced by the tumor cells. No evidence of distant metastases was
detected. Modified radical mastectomy with axillary clearance was done, with
uneventful postoperative course. On searching the Sudan medical literature, no
previous report of similar case was found. In conclusion, breast carcinoma,
though a rare entity, yet should be borne in mind if a firm breast lump was found
in a child. Fine needle aspiration cytology is effective to start with as a
diagnostic tool.
PMID- 27493335
TI - Meckel-Gruber syndrome: A rare and lethal anomaly.
AB - Meckel-Gruber syndrome is a rare and lethal autosomal recessive disorder
characterized by occipital encephalocele, postaxial polydactyly and bilateral
dysplastic cystic kidneys. It can be associated with many other conditions.
Antenatal ultrasound examination establishes the diagnosis by identifying at
least two of the major features described. We describe a female baby who had the
typical triad of Meckel-Gruber syndrome and died shortly after birth.
PMID- 27493336
TI - Etiology and clinical pattern of cervical lymphadenopathy in Sudanese children.
AB - Cervical lymphadenopathy (CLA) is a common childhood problem in clinical practice
which poses diagnostic difficulties to pediatricians. The aims of this study were
to determine the causes of CLA in Sudanese children and to evaluate the value of
routine laboratory tests in determining the etiology. Demographic and clinical
data were prospectively collected from eighty children with palpable cervical
nodes. Children were then subjected to complete blood count, ESR, Mantoux test,
aspiration cytology of a lymph node and serological tests for HIV agglutination
test, ELISA for Epstein-Barr virus and toxoplasma gondii. The age ranged 1-13
years with a mean of 5.8 +/-3.1SD years with no gender difference. Specific
etiologies of CLA were determined in 62.5% of patients. Ninety five percent of
the causes were due to non-specific reactive hyperplasia of lymph nodes (NSRH)
(37.5%), toxoplasmosis (27.5%), infectious mononucleosis due Epstein-Barr virus
(13.8%), tuberculous adenitis (10%), acute adenitis (6.2%), whereas malignancy
(Hodgkin's lymphoma) constituted 5% of causes of CLA. The clinical
characteristics were insignificantly associated with the causes of
lymphadenopathy (p>0.05). However, mobile lymph nodes were significantly
associated with inflammatory conditions (P<0.05). Inflammatory causes accounted
for the majority of the etiologies whereas Hodgkin's lymphoma was the only
identified malignancy. Laboratory tests such as, ESR, TWBC, hemoglobin and
Mantoux test should be used in adjunct with cytology and serology for diagnosis.
PMID- 27493337
TI - Audit of acute asthma management at the Paediatric Emergency Department at Wad
Madani Children's Hospital, Sudan.
AB - This audit of hospital care of acute wheeze and asthma aimed to assess the degree
of adherence of the acute care of the asthma patients to the published
international guidelines. Information was collected in six key areas: patient
demographics; initial asthma severity assessment; in-hospital treatment; asthma
prophylaxis; asthma education and emergency planning; and follow-up arrangements.
The area of initial asthma severity assessment showed defciencies in the clinical
measures currently used to verify case severity. In- hospital treatment on the
other hand was consistent with recommendations in the use of the inhaled beta-2
agonist salbutamol as bronchodilator, the discrete use of aminophylline and the
small number of patients ordered chest X-ray. However, the treatment was
incoherent with recommendations in the delivery method used for inhaled
bronchodilator in relation to the age group of treated patients, absence of
ipratropium bromide as a bronchodilator in the management and the large use of
antibiotics. Assessment of the areas of asthma prophylaxis, asthma education and
emergency- planning and follow-up arrangements illustrated that little efforts
were made to assure safe discharge, although these measures have been shown to
reduce morbidity after the exacerbation and reduce relapse rates and signifcantly
reduce hospitalizations, unscheduled acute visits, missed work days, as well as
improving quality of life. This audit emphasizes the need for the adoption of a
management protocol for acute asthma care in the emergency department based on
published international guidelines and the assurance of its implementation,
monitoring and evaluation using the right tools to improve patient care.
PMID- 27493339
TI - Managing the common and rare in paediatrics.
PMID- 27493340
TI - Overview of diagnosis, management and outcome of congenital hypothyroidism: A
call for a national screening programme in Sudan.
AB - Congenital hypothyroidism (CH) is the commonest preventable cause of mental
retardation in children worldwide. It continued to be a major health problem
amongst Sudanese children. The lack of a screening programme in Sudan may be the
major factor of missing the diagnosis in newborns with such a condition that can
present very subtle clinically, yet with poor neurodevelopmental consequences.
The outcome is very good when the condition is noticed early (in the first 2 - 3
weeks of life). However, the prognosis is guarded when the diagnosis is delayed,
with a squeal of different degrees of developmental delay depending on the
severity of the condition. In this overview, we tried to highlight the important
issues of screening, diagnosis and outcome with and without early management,
worldwide. We thereby send a call out for all paediatricians and endocrine
clinicians who work locally or outside Sudan to collaborate with the Sudanese
Society of Paediatrician as well as other stakeholders in Sudan to help
establishing a national screening programme for all common and preventable causes
of childhood illnesses which has devastating consequences such as CH.
PMID- 27493341
TI - Managing wheeze in preschool children: How difficult can it be?
AB - Wheeze is a common symptom in infants and preschool children. Up to 30% of
children wheeze at least once before the age of 3 years and 2% of those have it
severe enough to warrant hospital admission. Not only parents but also physicians
have difficulty in recognizing wheeze. Wrong diagnosis of the underlying
condition leads to inappropriate and unnecessary management and patient
morbidity. Asthma is the commonest underlying condition in children with wheeze,
but the differential diagnosis is quite broad and a systematic approach including
a good clinical history, thorough physical examination and appropriate
investigations are essential to reach the accurate diagnosis.
PMID- 27493342
TI - A review and practical application of evidence based medicine (EBM): Testicular
adrenal rest tumour.
AB - Nowadays, Medical practice is largely based on the best available evidence.
However, the evidence may not always be readily available and clinician and/or
other health allied professionals may need to learn how to search for it. This
article gives highlights on the very vast and growing subject of evidence based
medicine (EBM), followed by a practical application of searching for it in the
real life, in a situation when the available evidence is limited.
PMID- 27493343
TI - Sudanese female doctors in paediatrics.
AB - Though the number of female medical graduates has increased throughout the world,
their postgraduate professional achievements are said to be suboptimal. Our aim
is to look into the achievements of Sudanese female pediatricians and compare
them with their male counterparts. A cross sectional study was undertaken using a
questionnaire involving pediatricians working in the universities and Ministry of
Health, Sudan. Ninety five (65.1%) out of 146 pediatricians responded; 73 (76.8%)
were females and 22 (23.2%) were males. Thirty (41%) Of the females were in the
academic career. Only 2 (8.3%) out of 24 assistant professors were promoted to
associate professors and non of the four associate professors managed to become a
professor compared to 68% and 25% among males, respectively. Twenty three (76.6%)
of females compared to 31% of males had no publications. Nineteen out of 21
females (90.4%) who have been offered training opportunities abroad declined the
offer for family reasons. Fifty four (93%) female pediatricians declined to work
outside the capital state. No nursery facilities were available at work place.
The main reasons for inadequate achievements included family issues, cultural
obstacles, lack of mentorships and unsatisfying work environment and facilities.
Suggestions were put forward to improve on these problems. Though female doctors
are the majority of undergraduate and graduate students in Sudan, their
professional and academic achievements after specialization are not optimal
mainly for socio-cultural reasons and these need to be addressed.
PMID- 27493344
TI - Prevalence of smoking among school adolescents in Khartoum State.
AB - Tobacco is the single most important cause of chronic morbidity in the Developed
World. Tobacco use primarily begins in early adolescence, reportedly before the
time of high school graduation. By 2015 tobacco use is projected to cause 50%
more deaths than AIDS. A cross sectional school based survey was conducted in
primary and secondary school in Khartoum State. The study aimed to estimate the
prevalence of smoking in school adolescents and associated personal and social
factors. A total of 910 students with complete questionnaires were included in
the analysis, of whom 13.6% were found to be current cigarette smokers. Factors
that played role in initiation of smoking included smoking among parents, other
family members and close friends. School adolescents who have friends or parents
who smoke should be the main target for tobacco control. Smoking should become
public health priority in Sudan to educate adolescents and parents regarding its
hazards.
PMID- 27493345
TI - Visual acuity testability of children in Bama and Banki towns of Borno State,
Nigeria: The need to adopt HOTV protocol in school health programmes.
AB - Despite the importance of visual acuity testing in children, no standard testing
protocol was found for primary school pupils. Visual acuity screening was
conducted on 400 primary school pupils in Nigeria using the HOTV protocol, nearly
all the pupils 390/400 (97.5 %) had good binocular vision, only 10/400 (2.5 %)
had poor vision which were monocular. Of those with poor monocular vision, 6/10
(60 %) involved the right eye while 4/10 (40 %) the left eye; these pupils were
referred to the ophthalmologist for further evaluation. Because of its easy
usage, the HOTV protocol can be adopted by school health programmes especially
for the primary school pupils.
PMID- 27493346
TI - Pattern and outcome of renal diseases in hospitalized children in Khartoum State,
Sudan.
AB - In developing countries, renal diseases in children constitute important causes
of morbidity and mortality. In Sudan, data about patterns and outcome of these
disorders is generally scanty. We conducted this study to provide basic renal
data that may be utilized by researchers and health planners in a resource poor
setting. A retrospective record review of all pediatric patients, followed in
four teaching hospitals in Khartoum State over a five-year period (January 2000
June 2004), was achieved. In 150 hospitalized children a total of 200 renal
diagnoses were recorded. Urinary tract infection (UTI), occurring with other
underlying renal morbidities or isolated, was the commonest renal diagnosis
(20%). The second common renal disorders were nephrotic syndrome (NS) and
urolithiasis/stones accounting for 16% and 15.5% of cases, respectively. Acute
glomerulonephritis (AGN) and congenital anomalies were relatively less common
(12% and 10.5%, respectively). Other less frequently detected diseases were acute
renal failure (ARF) in 6%, chronic renal failure (CRF) in 4%, hereditary
nephropathies in 3.5% and renal tumors in 2.5%. There was a significant
correlation between the pattern of renal diseases and age of patients (P =0.001)
but not their gender or social class (P = 0.211 and 0.34, respectively). On
follow up, 99 out of 150 patients (66%) recovered their normal renal function,
6/150 (4%) remained with persistent proteinuria, 30/150 (20%) progressed to CRF,
10/150 (6.7%) died, and 5/150 (3.3%) were referred to radiotherapy department for
further management. Our data reflects geographical variations of patterns of
renal diseases in Sudanese children as in other countries. Many of these diseases
are preventable or potentially curable. Therefore, improvement of pediatric renal
services and training of health workers would help in early detection and
treatment of these conditions leading to reduction in their morbidity and
mortality.
PMID- 27493347
TI - Chronic immune thrombocytopenia in a child responding only to thrombopoietin
receptor agonist.
AB - Immune thrombocytopenia (ITP) is an acquired hematological disease in which the
body produces antibodies against its own platelets leading to platelet
destruction resulting in isolated thrombocytopenia. Childhood ITP may enter
complete remission in the majority of cases within six months from diagnosis.
However, 20-30% of affected children may develop chronic ITP (lasting for more
than 12 months). First line treatment includes intravenous immunoglobulin (IVIG),
corticosteroids or anti-D immunoglobulin. Second line treatment includes
splenectomy, immunosuppressive therapy or Rituximab. Recently two thrombopoietin
(TPO) receptor agonists (Romiplostim and Eltrombopag) are used to increase
platelet count in refractory chronic ITP by increasing platelet production in
bone marrow. Here is a case report on an 8 1/2 -year-old boy with refractory
chronic ITP who failed therapy with IVIG, corticosteroids, splenectomy and
Rituximab. He showed excellent response to treatment with TPO receptor agonist
(Romiplostim). His platelet count increased from less than 10 x10(3)/dl and
maintained between 100x10(3)/dl to 200x10(3)/dl after few weeks of starting
Romiplostim therapy.
PMID- 27493348
TI - Recurrent Kawasaki disease resistant to initial treatment with intravenous
immunoglobulin.
AB - Kawasaki disease (mucocutaneous lymph node syndrome) is a disease of unknown
etiology characterized by vasculitis which may affect the coronary arteries.
Young children are most commonly affected although the disease has been described
in adults. Kawasaki disease (KD) was first described by Dr Tomisaku Kawasaki in
1967. Since then, more cases have been reported worldwide, the majority being
from Japan. We report on a 6-year-old child with recurrent attacks of Kawasaki
disease which was initially resistant to the conventional treatment.
PMID- 27493349
TI - Meckel-Gruber syndrome: Antenatal diagnosis and ethical perspectives.
AB - Meckel-Gruber syndrome (MGS) is an autosomal recessive disorder characterized by
occipital encephalocele, polycystic kidneys and variable other congenital
malformations. We report on a Sudanese patient with MGS diagnosed by antenatal
ultrasound scan. Pregnancy was terminated at 25 weeks of gestation.
PMID- 27493350
TI - Successful separation of craniopagus conjoined twins.
AB - Craniopagus conjoined twins represent a rare phenom- enon of congenital
malformation/ dysmorphism. The clinical pathology of this complex entity is
reviewed and placed in perspective. Confusion surrounds the severity of
craniopagus conjoined twins especially in relation to the difficulty of
separation and subsequent outcome. Successful separation of craniopagus twins
remains a rarity, however modern neurosurgical tech- niques have created
opportunities for successful sepa- ration and brought hope for a normal survival
of these children who in the past were often left as historical footnotes or put
on display as oddities of nature. We report on a craniopagus conjoined twins from
Sudan who had been successfully separated.
PMID- 27493351
TI - Robert Archibald: A pioneer of tropical medicine in the Sudan: "I feel my heart
is in that country and my work too" [] (Archibald, writing about being away from
the Sudan during the First World War).
PMID- 27493352
TI - Building civilization starts from childhood.
PMID- 27493354
TI - Perinatal statistics of a 15-year period in the Central Region of Saudi Arabia.
AB - Perinatal statistics are one of the most essential outcome indicators used by
many developed countries in order to evaluate perinatal services provided to
newborns. In this retrospective study, we collected 15 years of perinatal data at
King Khalid University Hospital in Riyadh, Saudi Arabia in order to determine
stillbirth and other mortality rates in our institute and compare them with
international figures. A total of 58,073 babies were evaluated. Data were
collected from maternal and neonatal registry books and from perinatal mortality
and morbidity meeting reports between 1994 and 2008. Data were entered and
analyzed using Microsoft Office Excel 2007. The stillbirth rate was 11.7/1000,
early neonatal death rate was 3.4/1000, perinatal mortality rate (PMR) was
14.9/1000, and corrected PMR was 11.9/1000. Our rates were not significantly
different from those of North American and European ones. We noticed a dramatic
reduction in the corrected PMR in the last 3 years of the study because of
greater advancement in perinatal and neonatal care. Our mortality rates were
comparable to the North American and European rates which may reflect the quality
of perinatal care provided in our institute.
PMID- 27493353
TI - Surfactant therapy: the current practice and the future trends.
AB - The efficacy of surfactant preparations used in the prevention and treatment of
respiratory distress syndrome (RDS) is a well known fact; however, many
controversies remain. The debate over which surfactant to be used, when and what
is the best mode of delivery is still raging. Currently, animal-derived
surfactants are preferred and clearly recommended by various practice guidelines,
but new synthetic surfactants containing peptides that mimic the action of
surfactant proteins are emerging and they seem to have a comparable efficacy
profile to the natural surfactants. It is hoped that with further improvements,
they will outperform their natural counterparts in terms of reliability and cost
effectiveness. Early surfactant administration was shown to further reduce the
risk of RDS and its complications. However, as nasal continuous positive airway
pressure (nCPAP) is becoming increasingly the preferred first-line therapy for
RDS, the less invasive approaches of respiratory support along with early
selective surfactant administration (e.g. INSURE) appears to provide a better
option. Although neonatal RDS is still the main indication of surfactant therapy,
other pathological processes received considerable attention and major research
has been dedicated to explore the role of surfactant in their management,
Meconium aspiration syndrome (MAS) and congenital pneumonia are two worthy
examples. The most updated practice guidelines do recommend the use of
endotracheal instillation as the preferred mode of surfactant delivery. However,
aerosolization and other non-invasive methods are being investigated with some
success; nonetheless, further improvements are very much in need.
PMID- 27493355
TI - Traditional and spiritual medicine among Sudanese children with epilepsy.
AB - This cross sectional hospital based study, carried out simultaneously in Khartoum
and in Wad Madani, Al Gezira State, aimed to study the impact of spiritual
beliefs on explanation of the epilepsy etiology and the choices and methods of
spiritual and traditional medicine used in the management of epilepsy in Sudan.
The study included 180 care givers of whom 165 (91.7%) were mothers. Their ages
ranged between 30-40 years. The majority (88.8%) were educated and 60 (33.3%) of
them live in rural areas. Fifty eight (32.2%) attributed epilepsy to supernatural
causes while 41 (22.8%) and 90 (50%) thought that epilepsy is an untreatable and
contagious disorder, respectively. Traditional and spiritual medicine for the
treatment of epilepsy was used by 70.5%. The common spiritual technique used was
incantations (45.6%), spitting cure (37.2%) and ritual incensing (36.7%). Herbs,
black cumin (Nigella sativa), honey and olive oil were mentioned among others as
a traditional treatment for epilepsy. About two fifth (42.5%) started traditional
or spiritual treatment before seeking any medical advice. Nevertheless, only 2.4%
stopped the medical treatment as advised by the traditional healer. Fifty five
(43.3%) thought that spiritual and/ or traditional treatment were effective in
the management of epilepsy, 60(47.2%) found no difference while 12(9.45) got
worse. The majority of patients with epilepsy, although on medical treatment,
used traditional and spiritual methods as well. Traditional and spiritual healers
may be involved positively in the management of epilepsy and extensive public
educational programs are needed.
PMID- 27493356
TI - State of personal hygiene among primary school children: A community based cohort
study.
AB - Good personal hygiene in primary school children could be effective towards
preventing infectious diseases. This work examined personal cleanliness of
primary school children in Banki based on the following variables: bathing, state
of uniforms, hair, nails and oral hygiene. One hundred and fifty primary school
children in Banki community were selected using the cluster random sampling
method. Analysis of variance was used to compare means and to test for
significance of data, and coefficient of correlation to investigate the
relationship between cleanliness and age of subjects. There were 87 (58 %) boys
and 63 (42 %) girls in a ratio of 1.4:1. Ninety six (64 %) pupils belong to low
socioeconomic class. Whereas, 53 (35.3 %) were found within 11-13 years age
group, the overall mean age was 9 years (Standard deviation [SD] was 2.2), 95 CI
(7.0 - 11.0) years. Comparing means for the different categories of personal
hygiene, there was significant difference (F= 61.47, p < 0.0001). General
personal cleanliness in our participants improved with age, and a positive
significant correlation was observed between age and personal cleanliness in (r =
0.971, p = 0.026). In conclusion, significant number of primary school pupils in
Banki community had good personal hygiene, which was observed to be directly
proportional with age. Therefore, all efforts towards quality health education on
personal hygiene as a means of primary prevention of illnesses in primary school
pupils should be sustained.
PMID- 27493357
TI - Congenital neonatal chylothorax with hydrops fetalis treated with octreotide.
AB - Congenital idiopathic chylothorax is the most common form of pleural effusion in
neonates. It results from collection of lymphatic fluid in the pleural space
secondary to leakage from the thoracic duct or one of its main tributaries.
Chylothorax complicated by hydrops fetalis in a premature or term infant is an
uncommon, serious clinical problem. We report on two cases with congenital
chylothorax both treated with octreotide. One of the cases responded well to
octreotide treatment, while the other did not. We conclude that octreotide should
be considered in the treatment of neonatal chylothorax.
PMID- 27493358
TI - Kasabach - Merritt syndrome: A case report.
AB - Kasabach-Merritt syndrome is characterised by the combination of rapidly growing
vascular tumour, thrombocytopenia, microangiopathic haemolytic anaemia and
consumptive coagulopathy. The blood clotting disorder results from platelets and
other clotting factors of the blood being used up within the tumor. We report a
two- and- half month old Saudi female infant who presented with epistaxis,
conjunctival haemorrage and bilateral periorbital ecchymosis.
PMID- 27493359
TI - Marfan syndrome affecting a whole Sudanese family.
AB - Marfan syndrome (MS, OMIM 154700) is an autosomal dominant disorder of fibrous
connective tissue with striking pleiotropism and clinical variability. The
cardinal features occur in skeletal, ocular, and cardiovascular systems. We
describe a Sudanese family with the father and all his 4 children manifesting the
syndrome. To our knowledge, there were no previously reported MS cases from
Sudan.
PMID- 27493360
TI - Pioneers of paediatrics: Professor Salah Abdelrahman Ali Taha, MD (U of K), DCH,
PRCP (London), FRCP (Edin).
AB - This article highlights the contributions of Professor Salah Abdelrahman Ali Taha
(1927-1988), one of the pioneers in paediatrics in Sudan and Saudi Arabia. He
graduated from Kitchener School of Medicine (renamed, Faculty of Medicine,
University of Khartoum[U of K]) in 1952 and was awarded an MD from the U of K in
1973, having accomplished a survey on the prevalence and underlying causes of
childhood malnutrition in 14 villages. His impact was remarkable in establishing
child health services in Sudan and Saudi Arabia, and in laying the foundation of
the Department of Pediatrics, College of Medicine, King Saud University. He was
also an active researcher in various fields in child health, and was pioneering
in those related to nutrition. Following his return to Sudan, Dr Salah A Taha was
elected Member of Parliament from his rural district in Gezira State and was the
Speaker of the House of Parliament in 1986.
PMID- 27493361
TI - A pioneer of tropical medicine worldwide: Andrew Balfour, of Khartoum.
AB - This is an archival account of the career of Sir Andrew Balfour in Khartoum,
Sudan during the period 1902 to 1913. As the first director of the Wellcome
Tropical Research Laboratories in Khartoum during the period, Andrew Balfour was
tasked with establishing the laboratories and at the same time he was engaged in
founding the health services in Khartoum. Balfour worked in close collaboration
and support from Henry Wellcome and Reginald Wingate, the Governor General of the
Sudan. The energetic and meticulous sanitary work of Balfour had a remarkable
impact, with Khartoum declared mosquito-free by 1910. Establishing a research
base in the laboratories was met with many challenges but eventually Balfour
managed to recruit a team of dedicated researchers and to produce well-circulated
publications in tropical medicine. Balfour's work in Khartoum later lead him to a
distinguished career in tropical medicine. In 1923 he was appointed the first
Director of London School of Hygiene and Tropical Medicine. He was also elected
President of the Royal Society of Tropical Medicine and Hygiene (1925-27). Sir
Andrew Balfour, KCMG, CB, LL D (1873 -1931).
PMID- 27493362
TI - Professor Tigani El Mahi: Short biography and photos.
PMID- 27493363
TI - First Tigani El Mahi Memorial Lecture.
PMID- 27493364
TI - Food customs and cultural taboos.
PMID- 27493365
TI - Family and child welfare in relation to urbanization.
PMID- 27493366
TI - Report on a visit to Saudi Arabia.
PMID- 27493367
TI - Biomedical Research: Child health and nation's health.
PMID- 27493368
TI - Radiological imaging of disorders of sex development (DSD).
AB - The birth of a child with ambiguous genitalia is a matter of a medical and social
emergency to decide the appropriate sex rearing and eventually to prevent the
associated metabolic disturbances. It must be taken with immediacy and great
sensitivity. The pediatric endocrinologist should share the care with a team
consists of a pediatric urologist, or surgeon, a pediatric radiologist,
geneticist and a child psychiatrist or psychologist who should work closely with
the family. Ultrasonograpy is the primary modality for demonstrating internal
organs while genitography is used to assess the uterus, vagina, and any fistulas
or complex tracts. Magnetic resonance imaging (MRI) is used as an adjunct
modality to assess the internal gonads and genitalia. Early and appropriate
gender assignment is necessary for healthy physical and psychological development
of children with ambiguous genitalia.
PMID- 27493369
TI - Type 2 diabetes in Sudanese children and adolescents.
AB - The objective of this study was to determine the prevalence of T2 DM among
children and adolescents attending a paediatric and adolescent diabetic clinic in
Khartoum -Sudan and to find out the etiological factors, clinical presentation,
management and associated co morbidities. This was a retrospective, descriptive
hospital based study. The records of all children attending the clinic at Jabir
Abu Izz Diabetic Center from January 2006 to December 2009 were reviewed and
those who were diagnosed as type 2 DM were identified. Out of 985 patients 38
(4%) were labeled as having type 2 DM. Out of these, 35 (92.1%) had onset between
11-18 years of age and were all pubertal. Three patients (7.9%) were under 10.
Female to male ratio was 1.2: 1. Thirty two (84.2%) were from tribes of Arab
origin. There were no cases from tribes of southern Sudan of African origin. Risk
factors for obesity included: diabetes during pregnancy 15 (39.5%), large for
dates 16 (43%) small for dates 12(32%), family history of obesity 10 (26.3%),
lack of exercise 32 (87.6%), TV watching for long hours 32(84.3%) and consumption
of fast foods. Almost 70% were symptomatic at presentation. Co morbidities
included hypertension 22(57.9%), microalbuminuria 7 (18.4%), hyperlipidaemia
6(7%) and none had retinopathy. The mean HbA1C was 9.1% gm/dl. This data confirms
that T2 DM is emerging as a health problem among children and adolescents in
Sudan mostly as a result of obesity particularly among high socioeconomic group
in urban areas and more prevalent in certain ethnic groups.
PMID- 27493370
TI - Diabetic Ketoacidosis in children admitted to Pediatric Intensive Care Unit of
King Fahad Hospital, Al-Baha, Saudi Arabia: Precipitating factors,
epidemiological parameters and clinical presentation.
AB - Type I diabetes mellitus is the most common endocrine-metabolic disorder of
childhood and adolescence and diabetic ketoacidosis (DKA) can be life
threatening. The study aims at identifying precipitating factors, states
epidemiological features and describes clinical presentations in children with
DKA admitted to Pediatric Intensive Care Unit (PICU), King Fahad Hospital, Al
Baha, Saudi Arabia. The hospital records of 80 children admitted to PICU with DKA
between January 2000 and December 2004 were reviewed. Results were compared with
published data from Saudi Arabia and other countries. Age at admission ranged
between 8 months and 14 years (mean = 10.7 years). Female to male ratio was
1.22:1. Consanguinity was reported among 32(40%) of all admitted children's
parents. A family history of diabetes (either type 1 or 2) was reported in 59
(74%). The leading precipitating factor for DKA was infections (82.1%). An
episode of DKA was the first clinical presentation of diabetes among 52(65%). The
common presenting symptoms were: vomiting in 57(71.3%) and abdominal pain in 53
(66.3%). All children were dehydrated. Other signs included acidotic breathing
and tachypnea each in 60%. Only two children were comatose (2.5%). Three of
presenting cases were initially misdiagnosed as acute appendicitis before correct
diagnosis was established. Cerebral edema occurred in one child. There were no
deaths. DKA is an important cause of hospital admissions in our hospital, and 65%
of newly diagnosed cases present with DKA. More effort should be put to prevent
and reduce the incidence of DKA at initial presentation and later.
PMID- 27493371
TI - The pattern of anthropometric measurements among term newborn infants in Khartoum
state in relation to maternal factors.
AB - Anthropometric measurements of neonates are an important clinical tool for
diagnosis of abnormally small or large neonates. This study aimed at finding the
means of the anthropometric measurements among newborn babies in Khartoum state
and to relate the tendency of the anthropometric parameters to maternal and
paternal factors. This observational hospital-based study was carried out in 3
hospitals in Khartoum. Birth weights, crown-heel length and head circumference
were taken from term neonates and questionnaire-based interviews were conducted
with the mothers. Means of the sample and their associations with maternal and
paternal factors were calculated using SPSS. In addition, the means were compared
to WHO- MGRS (World health organization-multi growth reference standards). It was
found that the average male newborn weighed 3.16kg with a range of 2.4kg to
4.1kg, measured 48.91cm in length with a range of 46.1cm to 51.4cm and measured
34.74cm in head circumference with a range of 32.3cm to 36.9cm. As for the
females, the average newborn weighed 3.11kg with a range of 2.1kg to 4.2kg,
measured 48.49cm in length with a range of 45.1cm to 51.7cm and measured 34.16cm
in head circumference with a range of 32.3 to 36.4. These values were found to be
statistically significant when compared with the WHO- MGR. We conclude that there
was a difference observed in relation to Sudanese neonate's anthropometric
parameters compared to WHO-MGR standards. Growth charts specific for Sudanese
neonates are urgently needed.
PMID- 27493372
TI - Early outcome of pre-term neonates delivered at Soba University Hospital.
AB - In Sudan, several studies have been conducted on low birth weight, a few
concentrated on pre-term births per se. The objectives of this study were to
describe maternal and obstetric factors predisposing to pre-term delivery, to
determine the incidence of early neonatal complications, to identify causes of
early neonatal deaths and to determine survival rates relative to gestational age
and birth weight. A descriptive hospital-based study was conducted at Soba
University Hospital, over a seven months-period, from December 2003 to June 2004.
One hundred consecutively born premature infants were followed up from the moment
of delivery till the end of the first week of life. Chi squared tests and p
values, using confidence intervals of 95%, were used for analysis. Eighty four
mothers gave birth to 100 premature babies who were admitted to the Neonatal Unit
of Soba University Hospital. Pregnancy induced hypertension (38.1%), multiple
pregnancy ( 29%) and maternal infection ( 42.9%) were the main obstetric factors
predisposing to premature birth. Morbidity among the pre-term birth population
showed that respiratory distress syndrome was the main disease accounting for 36%
and 46.2% of the deaths, respectively. Neonatal jaundice, apnoea, and neonatal
infection occurred in 46%, 16% and 14% of the premature infants, respectively.
However, respiratory distress syndrome and apnoea have been strongly associated
with early neonatal mortality (P<0.05). A survival rate for the whole premature
infant study was 74% and survival rates increased with increasing gestational age
and increasing birth weight.
PMID- 27493373
TI - Cigarette smoking among medical students in The National Ribat University, Sudan.
AB - The problem of smoking among medical students is common worldwide, but the
pattern and extent of the problem varies from place to place. Data from Sudanese
medical students is limited. The aims of study was to know the extent of the
problem of smoking among medical students, its routes and how it can be reduced.
All students in the first and fifth year in the Faculty of Medicine, The National
Ribat University were asked to fill a questionnaire regarding their knowledge and
practice of smoking and when they started smoking. The questionnaire inquired
about the role of their peers and the staff to help them stop smoking. Two
hundred and forty (96%) of the first year students and 174 (94 %) of the fifth
year students responded by filling the questionnaires. Around 10 % of all
students smoke. Although non-smokers knew much about the problems of smoking,
many of the smokers did not. The main influence on students to start smoking was
from parents, siblings and friends. Eighty per cent of the smokers are willing to
give up smoking and they tried many times. The study showed that little effort
was made by the University Staff to help students stop smoking. Most students
started smoking in the high secondary schools. There is a need for family
community and institutional campaign to contain the problem of smoking.
PMID- 27493374
TI - An in vitro anticoagulant effect of Fenugreek (Trigonella foenum-graecum) in
blood samples of normal Sudanese individuals.
AB - Haemostasis is the process of forming clots in the walls of damaged blood vessels
to prevent abnormal bleeding and to maintain intravascular blood in a fluid
state. Fenugreek is largely universal staple herb, popular throughout history and
it has been consumed for treatment of different disorders. We aimed to study the
possible anticoagulant effect of Fenugreek aqueous extract in vitro by using
blood samples of normal individuals. In vitro anticoagulant effects of Fenugreek
aqueous extract (5%) in different volumes (25, 50 and 75 MUL) were examined in
the blood samples of normal individuals by measuring prothrombin time (PT). The
aqueous extract of Fenugreek was found to inhibit coagulation process in vitro
and significantly prolonged prothrombin time in a dose-dependent manner.
Fenugreek aqueous extract in different concentrations inhibits clot formation and
increases prothrombin time. Subject to further studies on efficacy and safety, It
can well be used, in the future, as a supplementary anticoagulant agent in
cardiovascular diseases and to prevent hypercoagulable states.
PMID- 27493375
TI - Congenital cystic adenamatoid malformation: A case report.
AB - We here report a rare case of congenital cystic adenamatoid malformation[CCAM].
This case presented early in the neonatal period with bilateral lung cysts and
have favorable outcome. However, the patient continued to be oxygen dependent for
more than six weeks.
PMID- 27493376
TI - Dandy-Walker malformation and neurocutaneous melanosis in a three-month-old
infant.
AB - Dandy-Walker Malformation (DWM) is a rare congenital malformation of the brain.
It is characterized by cystic enlargement of the fourth ventricle which is
communicating with an enlarged posterior fossa, cerebellar dysgenesis, high
tentorial insertion and hydrocephalus. Neurocutaneous Melanosis (NCM) is a
congenital neurocutaneous syndrome characterized by large or multiple melanocytic
nevi and benign or malignant melanocytic tumors of the leptomeninges. We report
three months old boy who presented with projectile vomiting associated with a
noticeable increase in head size. Several congenital nevi were seen all over his
body with evident signs of hydrocephalus. The association of DWM and NCM is a
rare complex, and to our knowledge, this is the eleventh case to be reported in
the literature. In this article, we discuss the proposed pathogenesis,
classification and management of the condition.
PMID- 27493377
TI - Professor Mansour Ali Haseeb: Highlights from a pioneer of biomedical research,
physician and scientist.
AB - The article highlights the career of Professor Mansour Ali Haseeb (1910 - 1973;
DKSM, Dip Bact, FRCPath, FRCP [Lond]), a pioneer worker in health, medical
services, biomedical research and medical education in the Sudan. After his
graduation from the Kitchener School of Medicine (renamed, Faculty of Medicine,
University of Khartoum [U of K]) in 1934, he devoted his life for the development
of laboratory medicine. He became the first Sudanese Director of Stack Medical
Research Laboratories (1952 - 1962). He made valuable contributions by his
services in the vaccine production and implementation programs, most notably in
combating small pox, rabies and epidemic meningitis. In 1963 he became the first
Sudanese Professor of Microbiology and Parasitology and served as the first
Sudanese Dean of the Faculty of Medicine, U of K (1963-1969). He was an active
loyal citizen in public life and served in various fields outside the medical
profession. As Mayor of Omdurman, he was invited to visit Berlin in 1963 by Willy
Brandt, Mayor of West Berlin (1957-1966) and Chancellor of the Federal Republic
of Germany (1969 to 1974). Also as Mayor of Omdurman, he represented the City in
welcoming Queen Elizabeth II during her visit to Sudan in February 1965. He also
received State Medals from Egypt and Ethiopia. In 1973 he was appointed Chairman
of the Sudan Medical Research Council, and was awarded the international Dr.
Shousha Foundation Prize and Medal by the WHO for his contribution in the
advancement of health, research and medical services.
PMID- 27493378
TI - Remembering for tomorrow: Professor Mansour Ali Haseeb.
AB - This is a highlight of the obituary ceremony in tribute to Professor Mansour Ali
Haseeb (1910 - 1973), organized by the Medical Students Association of the
Faculty of Medicine, the University of Khartoum (U of K). Professor Haseeb has
been the first Sudanese Professor and first Dean of the Faculty of Medicine. He
was an outstanding humane teacher, mentor and researcher, and was awarded the
international Dr. Shousha Foundation Prize and Medal by the WHO. He was also an
active citizen in public life and became Mayor of Omdurman City. The obituary
ceremony reflected the feelings of the medical community and included speeches by
Professor Abdalla El Tayeb, President of U of K; the Dean, Faculty of Medicine;
the Late Professor Haseeb's colleagues and students, His family representative,
and an elegy poem.
PMID- 27493379
TI - Henry Solomon Wellcome: A philanthropist and a pioneer sponsor of medical
research in the Sudan.
AB - Henry Solomon Wellcome, the famous drug manufacturer had a fascinating
association with the Sudan. Besides supporting tropical medicine research in this
country, he established an extensive project in the Sudan that aimed at combining
archeological excavations, philanthropy and social reform. This article is an
archives-based account on this side of Wellcome's association with the Sudan. The
article starts with Wellcome's early years in the American Midwest and the
evolution of his career and his rise as a world-renowned drug manufacturer. After
the battle of Omdurman, Wellcome visited Sudan in 1900 - 1901 where he offered to
support the establishment of the research laboratories which later came to be
known as the Wellcome Tropical Research Laboratories in Khartoum. He then became
directly involved in the planning and running of extensive archeological
excavations in the central Sudan. This project served as a field in which
Wellcome found an outlet for his philanthropy. More than 4000 labourers were
employed in Jebel Moya. Professional archeologists and anatomists were recruited
by Wellcome to supervise the work, and all the requirements in terms of equipment
were catered for. Wellcome devised a Savings Bank System whereby part of the
earnings of each labourer were saved to him till the end of the season. He also
introduced one of his innovations: aerial photography using box kite which was
used for the first time in archeology. Wellcome made it a rule that no applicant
should be turned away. The Camp Commandant had to find suitable work for each
applicant, including the handicapped who were assigned to appropriate jobs like
mending baskets or cutting grass for building huts. Wellcome's welfare work had a
significant impact on the local inhabitants of Jebel Moya. Henry Solomon
Wellcome, 1906. Oil painting by Hugh Goldwin Riviere. Credit: Wellcome Library.
PMID- 27493380
TI - An outline of the history of Medical Research Institutes in the Sudan.
PMID- 27493381
TI - Historical background and epidemiology of cerebrospinal meningitis (CSM).
PMID- 27493382
TI - Higher Degrees on Medical and Related Subjects.
PMID- 27493383
TI - Professionalism in medicine and hyposkillia.
PMID- 27493384
TI - Hyposkillia: A sign of sagging medical profession-A pediatric perspective.
AB - The practice of medicine since Hippocrates, the father of medicine (460-377 BC)
had the care of the patient in the core of its ideals which included scholarship;
confidentiality, altruism and no harm doing. These ideals evolved from individual
physician adoption to professional organization adoption. The medical profession
used to have autonomy, prestige, and values centered on patient care. With
societal changing values and the appearance of managed care and bioethics the
medical profession lost its autonomy, prestige and self regulation. This led to
widespread dissatisfaction among the profession members and reflected in
deficiency in education and training of medical students and young physicians and
resulted in deficiency of clinical skills required to deliver health care. This
situation has been referred to as hyposkillia. This sagging has been reported in
many countries worldwide and brought concern to many medical education
authorities and societies. In this paper nine cases are reported to demonstrate
that hyposkillia is also prevalent in our part of the world and show some
deficiencies in the clinical skills that are avoidable. Inadequacies in: accurate
history taking, complete appropriate physical examination, pertinent
investigation and sound critical reasoning in management planning, all precluded
optimum health care delivery initially in these cases. Many professional and
education authorities have suggested that the process of redemption of the
medical profession should start before admission to medical school by change in
admission requirements to include behavioral and social sciences, and that the
curricula in the medical schools should be redesigned to meet the changing
societal values and priorities. Teaching clinical skills should be a continuous
lifelong learning process from the medical school through training and into
practice. Modern technology is to complement and not to replace bedside teaching
and the patient should remain the best teacher for the physician.
PMID- 27493385
TI - The control of rheumatic fever and rheumatic heart disease: a call to raise the
awareness.
AB - Although the incidence of rheumatic fever (RF) and rheumatic heart disease (RHD)
has declined in the developed world and many developing countries, yet it is
still high in many countries including Sudan. The decline of frequency of RF in
these countries is largely due to improved medical services leading to wide use
of antibiotics to treat bacterial pharyngitis. In many developing countries, the
incidence is decreased due to development of integrated control programs.
Depending on secondary prophylaxis alone was shown to be ineffective, therefore,
many countries, including Sudan initiated control programs that utilize both
primary and secondary prevention together with increasing awareness and
surveillance. The new program started in 2012 in Sudan in order to achieve its
goal of reducing mortality of RHD by 25% in individual less than 25 years of age
by year 2025. This article throws light on RF and RHD and its control program in
Sudan.
PMID- 27493386
TI - Patent ductus arteriosus in preterm infant: Basic pathology and when to treat.
AB - The incidence of patent ductus arteriosus (PDA) in premature neonates varies
according to the gestational age and respiratory status. Failure of PDA closure
in preterm infants with respiratory distress syndrome results in a left to right
shunt across the duct which may lead to pulmonary congestion and deterioration in
respiratory status. Although indomethacin and ibuprofen are the main stay of
medical treatment, conservative approach by restricted fluid and applying
continuous positive airway pressure (CPAP) may be effective in prevention of PDA
without complication. The daily clinical round debate on how to diagnose, when,
and how to treat PDA in preterm neonates will be discussed with details in this
review.
PMID- 27493387
TI - Teaching professionalism in medicine: what, why and how?
AB - The increased attention that "medical professionalism" has received lately
exposes the deficit in our educational system and indicates the need for more
work to be done to ensure an effective teaching and assessment of this
competency. The concerted efforts made by many reputable organizations are great
steps in the right direction. Nonetheless, many medical schools are still lagging
behind. Literature has been clear about the importance of formal teaching in
establishing professional behaviors in the medical school graduates; failing in
this regard is certain to have unfavorable outcomes. Furthermore, current
literature suggests many teaching strategies and assessment tools that can help
in achieving this goal. However, many inadequacies are still there. Teaching
professionalism requires, in addition to an explicit core curriculum that spans
the continuum of medical education, special efforts in terms of imparting the non
cognitive skills as well. Respectable role-models play a major part in this
process. Helping students to reflect on the real life encounters in a safe
environment is, probably, one of the most effective tools at our disposal. Many
obstacles that may hinder this educational endeavor have been described in the
literature. Negative role models and the "hidden curriculum" are among the most
dreaded ones and they deserve an extra effort to overcome.
PMID- 27493388
TI - Cystic fibrosis in Sudanese children: First report of 35 cases.
AB - Cystic fibrosis is the most common severe genetic disorder among children of
European descent. It is much less common in Africans and Asians. It affects most
critically the lungs causing chronic lung disease, failure to thrive and social
deprivation. This is a retrospective review of 35 Sudanese patients with
confirmed cystic fibrosis. About 60% of cases presented before the age of 5 years
and male to female ratio was 1.7:1.0. Consanguinity was reported in 25 of the
families. The main presenting features were productive cough, wheeze and
clubbing. The chest X-ray showed variable degrees of hyperinflation, collapse,
cystic, fibrotic changes and bronchiectasis involving both upper and lower lobes
with blurring of cardiac border and hilar vasculature in the majority of cases.
The sweat chloride was between 70 and 140 mmol/l in 83% of the patients (positive
> 60 mmol/l). Three patients underwent DNA study and confirmed to have cystic
fibrosis transmembrane conductance regulator (CFTR) gene mutations. Gene study
was not available for the rest of the patients. To our knowledge this is the
first report of confirmed cases of cystic fibrosis in Sudanese patients.
PMID- 27493389
TI - Vitamin A-rich porridge for Boarding Khalwa students with night blindness.
AB - Khalwa is a non-governmental boarding school specialized in teaching Quran to
Sudanese children. Food supply to Khalwa is completely dependent on donations.
Students are fed on low cost and low nutritional value diet made of sorghum flour
porridge and a stew made of dry okra, onion and oil. The incidence of night
blindness among these students is reported by the Nutrition Department of the
Federal Ministry of Health, Sudan, in 2005 as 0.9%. In this study we interviewed
and examined 453 Khalwa students in Umbada area, however blood sampling for assay
of vitamin A level was not acceptable by the Khalwa authorities. Thirty four
students (7.5%) showed clinical evidence of Vitamin A Deficiency (VAD), 67.6% of
them for a period of less than 6 months which was consistent with their stay in
Khalwa. Vitamin A fortified sugar is used in Kenya, Zambia, South Africa and
Honduras but it is costly and sugar-containing foods and drinks are not in common
use by Khalwa students. To supply students with a good amount of vitamin A, we
prepared a new porridge formed of sorghum flour; peeled, chopped and boiled
pumpkins in addition to their traditional stew. One meal per student contained
250 grams of sorghum flour and 125 grams of pumpkin which supplies 611MUg (10891
I.U.) of vitamin A according to the USDA SR-25 composition tables (>100% Daily
Value). Compared to the old porridge, there was significant differences (P <0.05)
in vitamin A, carbohydrate, protein, fiber, fat, ash and moisture contents. All
students accepted the taste of the new porridge and 91.2% agreed that it is not
difficult to prepare. We conclude that adding pumpkins to Khalwa porridge is cost
effective and may help preventing VAD and its deleterious effects on vision and
health.
PMID- 27493390
TI - The quality of life among Sudanese children with epilepsy and their care givers.
AB - In the past few years, there has been a progressive increase in appreciation of
the importance of quality of life (QOL) especially among patients with epilepsy.
This issue had not been addressed in Sudanese children with epilepsy. We here aim
to assess the quality of life in Sudanese children with epilepsy and their family
care giver. This study was conducted in 2011 at the Epilepsy and Neurodisablity
Out-patient Clinic at Saad Abualila University Hospital, Sudan. The study
included 100 Children with epilepsy, and their care givers, whose age was between
6-18 years and had seizure for more than one year. The questionnaire used
contains 27 questions; it was divided into four sections: impact of epilepsy and
treatment, impact on the child development, impact on parents and impact on the
family. For each question there were two dimensions: the frequency of the problem
and the concerns that it causes. The total score ranges from 0 to 54. A combined
total scale scores were calculated. The commonest concern regarding epilepsy was
that the child may injure oneself, followed by that the child may stop breathing
or develop brain damage or even die. The commonest concern regarding treatment
was that medication may cause reduced alertness. The relevant mean scores in
frequency and concern were 5.77 and 5.83 out of 10 respectively. In the child
development domain, the commonest concern was that the child may become more
moody and the related mean scores in frequency and concern were 9.36 and 9.32 out
of 18. The commonest concern to parent was decreased ability for self care with
relevant mean scores in frequency and concern of 3.14 and 3.16 out of 10. The
commonest concern to the family was that the child needs to be more closely
watched than other children. The mean scores here in frequency and concern were
5.37 and 5.44 out of 14. The group with epilepsy and associated co morbidities,
longer seizure and treatment duration had consistently higher mean scores which
were proved to significantly lower their QOL. There is a significant decline in
the quality of life among Sudanese children with epilepsy and their family care
giver. Psychosocial consultation, family support programs and health education
for parent, teachers and publics about different aspects of epilepsy need to be
addressed through mass media.
PMID- 27493391
TI - Physical methods used by Sudanese mothers in rural settings to manage a child
with fever.
AB - Although the mainstays of antipyretic treatments are drugs such as paracetamol
and ibuprofen, physical methods are also used. These include tepid sponging,
removing clothes, and cooling the environment with fans to improve ventilation.
The objective of this study is to assess the physical methods used by Sudanese
rural mothers to manage a child with fever. A cross-sectional descriptive study
was designed and conducted within 6 months; it involved 332 mothers of children
under five. The data were collected through using a standardized administered
questionnaire and focus group discussion and analyzed by statistical package for
social science version 15.0 (SPSS). Tepid sponging was used by 47% of the
interviewed mothers. 15% of the mothers increased fluid intake, 7% bathed the
child and 5% put the child in light clothes. 59% of mothers applied tepid
sponging on head, 33.9% on all the body, 3.7% and 2.2% on groin area and axilla,
respectively. The majority of mothers (86%) used water from refrigerator or zeir
[water clay pot] for applying tepid sponging, 9% used tap water, and 3% used ice
water. In conclusion, this study revealed that the common physical treatment
method for fever used by mothers was tepid sponging with inappropriate
application.
PMID- 27493392
TI - Neonatal respiratory distress in Omdurman Maternity Hospital, Sudan.
AB - Neonatal respiratory distress (NRD) is a common neonatal problem, which is
responsible for high morbidity and mortality. There are few published studies in
developing countries addressing neonatal respiratory distress. There is no
previously published study in Sudan on this problem. The objective of the study
is to determine the frequency, different causes, immediate outcome. It was a
prospective, descriptive, cross sectional hospital-based study which was carried
out in neonatal intensive care unit (NICU) of Omdurman Maternity Hospital,
between February-March 2013. The study enrolled all Sudanese newborns from 0-28
days including normal, low and high birth weight of different gestational ages
admitted to the neonatal intensive care unit and diagnosed as neonatal
respiratory distress. The frequency of NRD was calculated, the causes and
immediate outcome were determined. Results showed that the frequency rate of NRD
was (4.83%) among the total number of hospital (2071) live births during the
period of the study. The commonest causes were transient tachypnoea of the
newborn (TTN) in 28% of cases, sepsis in 24% of cases and hyaline membrane
disease (HMD) in 15% of cases. The outcome of NRD was: cure in 56% of cases,
death in 36% of cases, and patients discharged with complications in 8% of cases.
In conclusion, the study confirmed the importance of NRD with a frequency rate of
4.83%, morbidity of 8% and mortality of 36% of cases. The causes and immediate
outcome were determined and discussed. Some recommendations were suggested in
order to reduce its frequency, morbidity and mortality.
PMID- 27493393
TI - Fast food intake and prevalence of obesity in school children in Riyadh City.
AB - Childhood obesity has become a new challenge for healthcare providers. The issue
is not limited to certain parts of the world; its prevalence is increasing
worldwide. The causes of obesity are poorly understood and continue to be debated
and studied. It is a multifactorial disorder which involves dietary, behavioral,
environmental as well as genetic factors. The increased consumption of more
energy-dense, nutrient-poor foods with high levels of sugar and saturated fats,
combined with reduced physical activity, have led to high obesity rates among
children. The aim of this study was to assess the effect of dietary intake on the
occurrence of childhood obesity, and study other associated factors including the
education, occupation and income of parents and the living status. Normal healthy
school girls (n =196) and school boys (n = 85) between the age of 6- 15 were
recruited for the study. We found that obesity among children in Riyadh City was
significantly associated with fast food intake (p = 0.0280). It was also observed
that 72.5% of the overweight or obese students consumed fast food at least 4
times/week, and the other 15.9% were taking fast food 1- 3 times/week, while only
11.6% of the same overweight or obese group did not consume any fast food/ week.
Father's and mother's occupations were not significantly correlated to their
children's body weight. The prevalence of childhood obesity is changing and
increasing yearly and is attributed to the nutritional risk factors for the Saudi
school-age children. It is interesting to know that most of overweight or obese
school students belonged to the families of highincome. Parents must take
necessary precautions for the diet of their children and should adopt healthy
life style in order to prevent or manage obesity of their children.
PMID- 27493394
TI - Crimean-Congo hemorrhagic fever (CCHF) in Southern Kordofan.
AB - Crimean-Congo hemorrhagic fever (CCHF) is a disease that poses a great threat to
public health owing to its high mortality rate (30-70%), mode of transmission and
geographic distribution. Here, we report on a nine years-old Sudanese boy from
Southern Kordofan State who presented with Jaundice, high-grade fever, severe
headache, abdominal pain and a history of hematemesis. The diagnosis of CCHF was
confirmed based on clinical and serological findings.
PMID- 27493395
TI - Pentalogy of Cantrell: case report and review of the literature.
AB - Pentalogy of Cantrell is a syndrome that consists of five anomalies: a midline,
upper abdominal wall abnormality; lower sternal defect; anterior diaphragmatic
defect; diaphragmatic pericardial defect, and congenital abnormalities of the
heart. The pathogenesis of this condition is not fully known yet, associations
are common with this condition and treatment is extremely challenging. Prognosis
and outcome depends on the type of the pentalogy of Cantrell and associated
cardiac anomalies. It can be diagnosed reliably by antenatal ultrasound during
the first trimester. We describe a Sudanese baby of undetermined sex who had the
typical features of pentalogy of Cantrell and died shortly after birth.
PMID- 27493396
TI - Managing traumatic brain injury in children: When do we need a computed
tomography of the head?
AB - Accidents still represent a major cause of death and disability in children. The
resultant traumatic brain injury (TBI) usually needs a multidisciplinary approach
of management. Although computed tomographic (CT) head scan is generally a
preferred investigation in TBI, however, clear guidelines are required to help
decision making by different team members on "when a head CT scan is needed", its
limitations, and "when it is likely to be informative". The answers to these
queries are highlighted, in the present article, with other aspects of treatment
of children with TBI. This article discusses different worldwide-accepted
approaches for managing children with TBI, and places special emphasis on the
issue of "indications for a head CT scan".
PMID- 27493397
TI - Albert Chalmers: Perpetual honours for a prominent tropical medicine career in
the Sudan.
AB - This article starts with brief review of Albert Chalmers' early career in
tropical medicine until he was appointed Director of the Wellcome Tropical
Research Laboratories in Khartoum (WTRLK) in 1913, succeeding Andrew Balfour.
Then the article explores how Chalmers faced the challenges and managed to
establish a solid research base under very harsh conditions. Most of his
directorship was during the First World War, with shortage of staff and increased
routine work load. In spite of these constraints, Chalmers managed to establish a
base for research in tropical medicine in WTRK. Chalmers' research concentrated
on the taxonomy and pathogenicity of bacteria and fungi but he also worked on
miscellaneous dermatological disorders and on sleeping sickness. His papers
reflect a wide range of knowledge and deep understanding of the topics he was
covering. His work on the classification of pathogenic fungi was widely
recognized. He tried different preparations of vaccines for cerebrospinal
meningitis but with the technology available at the time he could not produce a
potent vaccine. Chalmers' papers reflect the tremendous effort exerted in their
production. Chamers resigned from WTRLK in 1920 and died of acute infective
jaundice in the same year. In 1921 his widow, gave L500 to the Royal Society of
Tropical Medicine and Hygiene (RSTMH) in memory of her husband. The RSTMH Council
decided to devote this money to the foundation of the Chalmers Memorial Medal.
PMID- 27493398
TI - Remembering the first doctors worldwide who offered their lives fighting Ebola
virus epidemic.
PMID- 27493399
TI - Health care professional development: Working as a team to improve patient care.
AB - In delivering health care, an effective teamwork can immediately and positively
affect patient safety and outcome. The need for effective teams is increasing due
to increasing co-morbidities and increasing complexity of specialization of care.
Time has gone when a doctor or a dentist or any other health practitioner in
whatsoever health organization would be able to solely deliver a quality care
that satisfies his or her patients. The evolution in health care and a global
demand for quality patient care necessitate a parallel health care professional
development with a great focus on patient centred teamwork approach. This can
only be achieved by placing the patient in the centre of care and through sharing
a wide based culture of values and principles. This will help forming and
developing an effective team able to deliver exceptional care to the patients.
Aiming towards this goal, motivation of team members should be backed by
strategies and practical skills in order to achieve goals and overcome
challenges. This article highlights values and principles of working as a team
and principles and provides team players with a practical approach to deliver
quality patient care.
PMID- 27493400
TI - The prevalence and risk factors of retinopathy of prematurity among preterm
babies admitted to Soba Neonatal Intensive Care Unit.
AB - This is a prospective hospital based study conducted in Soba University Hospital
(SUH), Neonatal Intensive Care Unit (NICU) between January 2012 and January 2013,
to determine the prevalence and risk factors of retinopathy of prematurity (ROP)
among preterm babies admitted to Soba NICU and to assess the outcome of those
babies. Ninety-two neonates with gestational age less than 34 weeks at birth were
included in the study. Thirty-three of them were males and 59 were females. All
of them were admitted to the NICU due to prematurity. Data was collected in a
structured questionnaire. Thirty-four infants (37%) developed ROP in one or both
eyes; 12 (35.3%) of them developed stage 3 and underwent laser therapy, 2 of them
had aggressive posterior form, which was treated with Evastin injection. Seven
(20.3%) neonates diagnosed as stage 2, and 13 (37.7%) had stage 1. Statistically,
there were significant relationships between ROP and gestational age, birth
weight (BW), oxygen therapy, sepsis, and blood transfusion (p=0.000). No
significant relationship was found between the occurrence of ROP and sex of the
baby, respiratory distress syndrome (RDS), hyperbilirubineamia, intraventricular
haemorrage (IVH) and necrotizing enterocolitis (NEC), p >0.000 in all of them.
The prevalence of ROP in this study was 37%. Low BW, low gestational age, oxygen
therapy, and blood transfusion were all significant risk factors for ROP. ROP
should be highlighted in Sudan, and screening program should be recommended for
all premature babies.
PMID- 27493401
TI - Risk factors of low birth weight at three hospitals in Khartoum State, Sudan.
AB - The aim of this study was to determine the percentage of women who give birth to
low birth weight (LBW) children and to study the association of the different
risk factors with LBW in three of large hospitals in Khartoum State, Sudan. This
was a cross sectional study of 381 women. Three groups: 151, 130 and 100 women,
who gave birth to live children, were selected from Alsuadi Teaching Hospital,
Khartoum Teaching Hospital and Alribat University Hospital, respectively. Data
were collected through structured interviews and the birth weights were recorded
as measured by midwives. Uni-Multi variate analysis of the data was performed
using SPSS 19. Permissions were taken from hospital administration and the
participants before the conduction of the research. 13% of live born children
were of low birth weight. The main risk factors for low birth weight in the study
were the lack of adequate education (OR= 1.9) gestational age (OR= 5.5), type of
pregnancy (OR= 9.6), presence of hypertension (OR= 3.6), renal disease (OR= 2.1),
bleeding during pregnancy (OR= 6.1) and presence of moderate or severe anemia
(OR= 3.19). While Adequacy of antenatal care (ANC) visits, presence of diabetes
mellitus during pregnancy, smoking and malaria in the first three trimesters,
presence of previous children and spacing were all found to be statistically not
significant risk factors. Many of the risk factors are modifiable and can be
prevented by improvement of the health care during pregnancy.
PMID- 27493402
TI - Acute kidney injury in asphyxiated neonates admitted to a tertiary neonatal unit
in Sudan.
AB - Acute kidney injury (AKI) is a recognized complication of birth asphyxia. Early
recognition of AKI is important in asphyxiated neonates as it helps in early
intervention and appropriate management. The aim of this study was to determine
the pattern of AKI in asphyxiated neonates and its relation to the grade of
Hypoxic Ischemic Encephalopathy (HIE). This was a prospective hospital based
study, conducted in the neonatal intensive care unit (NICU) at Gafaar Ibn Auf
Children's Specialized Hospital during the period between January 2013 and
December 2013. A total of 85 full term asphyxiated neonates who were admitted in
NICU and diagnosed as HIE were enrolled in this study. with 50 (58.8%) less than
7 days of age, 31(36.5%) between (8-15) days and 4(4.7%) between (16-28) days.
Males were found to be more affected than females (58.9% and 41.1%) respectively.
Spontaneous vaginal delivery was the mode of delivery in 48(56.4%), assisted
vaginal delivery in 14(16.5%), emergency caesarian in 19(22.4%) and elective
caesarian section in. Percentage of AKI in those babies was 54.1%(46). With
30(65%) from those had non-oliguric type. Ten babies (21.7%) had serum creatinine
between (1.5 - 2mg/dl), 29 (63.04%) between (2 - 3mg/dl) and 7(15.22%) between (3
4mg/ dl). This means that the majority of patients presented in injury stage.
Hyperkalemia was found in (37.6%), hyponatremia in (27.1%) and hypocalceamia in
(25.8%). Most of the babies with AKI had stage (ii) HIE. All babies were treated
conservatively and 4(8.6%) died. In conclusion AKI was observed to be a common
complication in asphyxiated neonates.
PMID- 27493403
TI - The use of vital signs as predictors for serious bacterial infections in children
with acute febrile illness in a pediatric emergency setting in Sudan.
AB - Distinguishing children with serious infections from those with milder, self
limiting febrile illnesses remains a daily challenge in primary care and hospital
emergency department. Measurement of vital signs is recommended as part of this
assessment. To determine whether vital signs can predict children with serious
bacterial infections, we studied the data of children aged 1 month to < 16 years
presented who with acute febrile illness to a Pediatric emergency department in
Sudan. Sample size was 150 patients. The severity of infection was classified as
serious or not serious bacterial infection. Vital signs and oxygen saturation
were recorded and compared to the final outcome of these children. Data analyzed
bivariably and multivariably using regression analysis. Ten percent of patients
were classified as having serious bacterial infection. Tachycardia and tachypnea
were the most sensitive and specific in predicting serious bacterial infections
with (80%, 86.6 % sensitivity) and (97.4%, 83.7% specificity), respectively. High
temperature, severe hypoxemia and hypotension were the least sensitive but highly
specific signs of serious bacterial infections. As a conclusion, vital signs can
be used to differentiate children with serious bacterial infections from those
with non-serious bacterial infections in pediatric emergency departments and has
comparable sensitivity to more complicated triage systems.
PMID- 27493404
TI - Carbaodeim: A natural haematinic blend for treatment of dimorphic anemia of
malnutrition.
AB - Sudanese nomadic tribes living in the Sahara Region west of Khartoum State depend
completely on food made of sour milk and other milk products cooked with onion
and dried meat. This is usually added to a porridge made of sorghum flour. Goat
and sheep milk is the main component and green vegetables are not commonly taken
with this meal. Adults, who move out of their residential areas may have access
to other types of food in towns and cities while mothers and children, staying
always at home, do not have similar chances. Furthermore, in these dessert areas
there is always difficulty in reaching health care facilities and getting
medicines. Children from these areas who presented to Ombada Teaching Hospital -
west of Omdurman- had very low hemoglobin and their peripheral blood picture
showed dimorphic type of anemia. In the search for locally available ingredients
that can prevent the occurrence of this type of anemia among the affected
population, we studied the constituents of the commonly available fruits and
vegetables in the area. We succeeded to formulate a blend (Carbaodeim) made of
Carrots (25 gm), Baobab (100 gm) and Godeim (100 gm) which is found to contain
iron (34.8 mg), folic acid (2.5 mg), ascorbic acid (372.8 mg), vitamin A (7000
mg), calcium (896.7 mg) and potassium (1910 mg), with many other components that
have high nutritional value. This blend is easy to make, safe, nutritious,
refreshing and cost effective. Carbaodeim is a naturally available and cost
effective haematinic blend that might be added to the food menu of nomadic people
as well as patients admitted to hospital with malnutrition or dimorphic type of
anemia.
PMID- 27493405
TI - Risk factors for neural tube defects in Riyadh City, Saudi Arabia: Case-control
study.
AB - Both genetic and non-genetic environmental factors are involved in the etiology
of neural tube defects (NTD) which affect 0.5-2/1000 pregnancies worldwide. This
study aimed to explore the risk factors for the development of NTD in Saudi
population, and highlight identifiable and preventable causes. Similar studies
are scarce in similar populations ofthe Arabian Peninsula and North Africa. This
is an unmatched concurrent case-control study including NTD cases born at King
Khalid University Hospital, Riyadh during a 4-year period (2002-2006). The case
control study included 25 cases and 125 controls (case: control ratio of 1:5).
Years of formal education, employment, household environment (including
availability of air conditioning) and rate of parental consanguinity did not
differ between mothers of cases and controls. Significantly higher proportion of
mothers of cases had history of stillbirth compared to control mothers (16% vs
4.1%, P=0.02). Also family history of hydrocephalus and congenital anomalies were
more prevalent in cases than controls (P values=0.0000 and 0.003, respectively).
There was significant protective effect of periconceptional folic acid
consumption both prior to conception (OR 0.02, 95% CI 0.00-0.07) and during the
first 6 weeks of conception (OR 0.13, 95% CI 0.04-0.39). Further research,
including a larger cohort, is required to enable ascertainment of gene-nutrient
and gene environment interactions associated with NTD in Saudi Arabia.
PMID- 27493406
TI - The neurologic aspects of hypomelanosis of Ito: Case report and review of the
literature.
AB - The term hypomelanosis of Ito (HI) is applied to individuals with skin
hypopigmentation along the lines of Blaschko. Although it was originally
described as a purely cutaneous disease, subsequent studies describing HI
reported a 33% to 94% association with multiple extracutaneous manifestations,
mostly of the central nervous and musculoskeletal systems. This leads to
characterization of HI as a neurocutaneous disorder. We report a 10-year-old boy
who presented with constellation of multiple congenital anomalies including
facial dysmorphism, skin hypopigmentation, musculoskeletal, and nervous system
abnormalities. The latter manifested as hypotonia, generalized seizures, and mild
mental retardation. Cranial magnetic resonance imaging revealed normal finding
initially, however; follow-up diffusion weighted images were suggestive of a
possible iron accumulation. The facial phenotype coupled with the bilateral
globus pallidi lesions were never been reported in association with HI. Thus, our
patient represents a possible novel example of HI.
PMID- 27493407
TI - Apert Syndrome: Late presentation and treatment challenges.
AB - Apert syndrome is a rare autosomal dominant disorder characterized by
craniosynostosis, craniofacial anomalies, and severe symmetrical syndactyly of
the hands and feet. Anomalies of the viscera, skeleton and cardiovascular system
have also been reported... Untreated craniosynostosis leads to inhibition of
brain growth and an increase in intracranial and intraorbital pressure. Most
cases are sporadic, resulting from new mutations with a paternal age effect. The
prognosis of Apert Syndrome depends on the severity of brain malformation and
early surgical interventions. We describe a Sudanese infant with Apert syndrome
who presented for the first time at the age of three months and had limited
options for intervention.
PMID- 27493408
TI - Trisomy 18 syndrome: Towards a balanced approach.
AB - Trisomy 18 is a relatively common autosomal trisomy syndrome. It is due to either
full or partial presence of an extra copy of chromosome 18. Its prevalence
correlates positively with advanced maternal age. Affected infants usually
exhibit a variable pattern of anomalies including growth restriction, marked
psychomotor and cognitive disability and an array of physical findings including
characteristic craniofacial features, clenched fists with overriding fingers,
small fingernails, underdeveloped thumbs, short sternum and heart and kidney
anomalies. The majority of these infants die within the first year of life; only
5% to 10% of them survive longer. Their death is primarily due to cardio
respiratory failure. In this case report of trisomy 18 we tried to highlight the
importance of antenatal diagnosis and to emphasize the need for proper counseling
at different points of time starting from the moment the condition is suspected
until the point when diagnosis is confirmed and thereafter.
PMID- 27493409
TI - Transient hyperphosphatasemia in children.
AB - Transient Hyperphosphatasemia (TH) is a benign condition in which serum alkaline
phosphatase (ALP) is transiently elevated in the absence of other systemic
diseases. It mainly occurs in infants and children and very rarely seen in
adults. The differential diagnosis may include liver, bone, kidney, intestinal,
placental and blood diseases as well as other serious conditions as well as bone
fracture due to accidental or non-accidental injuries. In this report, we present
tow of our patients with TH and compare their clinical course with the natural
history of TH described in literature. We also provide a focused review, in
relevance to our presented cases, of this disease, which is rarely encountered in
clinical practice.
PMID- 27493410
TI - Dr Abdeen Khairy: The first doctor, worldwide, who gave his life fighting Ebola
epidemic in 1976.
PMID- 27493411
TI - Fighting the first Ebola virus epidemic in the World in 1976: Memoirs of a young
doctor.
PMID- 27493412
TI - Dr Mahgoub Osman Karrar who wrote the first clinical report on Ebola virus
disease worldwide.
PMID- 27493413
TI - A Clinical Report of The Outbreak of The Haemorrhagic Fever Which Occurred in
Maridi Area, Equatoria Provinces, in The Southern Region of The Sudan.
PMID- 27493414
TI - Loss of a Stethoscope: Ebola memoirs.
AB - Loss of a Stethoscope is a real story highlighting the first epidemic of Ebola
virus in the World, narrated by an eye witness. It occurred in southern Sudan
(currently, South Sudan), mainly in Maridi. A Stethoscope that the people of
Sudan are in an impelling need for was lost there. The hero is Dr. Abdeen Kairy,
the doctor who managed the epidemic on his own at Maridi Hospital. He was an
ebullient and graceful doctor who steps in confidence, determination and bravery
towards his determined goal. He breaks through risks and disdains all hardships.
He treated the lethal idiopathic disease. He got infected and died as the Martyr
of Duty, Honor and Heroism.
PMID- 27493415
TI - Paediatric neurology at the confluence of the Blue and White Niles.
PMID- 27493416
TI - Managing childhood epilepsy in a resource-limited setting: A pragmatic approach.
AB - Epilepsy is a complex neurological disorder. Its burden constitutes a major
public health problem in resource-limited countries like Sudan. When it affects
children, the challenges surrounding its diagnosis and management are enormous
resulting in large numbers of patients missing out on adequate treatments.
Epilepsy has the potential of not only adversely affecting the physical health of
children but of also impacting negatively on their emotional, cognitive and
social well-being. A pragmatic approach based on sound clinical skills of how to
accurately diagnose epilepsy, as a priority, coupled with the choice of a cost
effective, wide spectrum and efficient anti-epileptic drug, is recommended.
PMID- 27493417
TI - Developmental regression in autism spectrum disorder.
AB - The occurrence of developmental regression in autism spectrum disorder (ASD) is
one of the most puzzling phenomena of this disorder. A little is known about the
nature and mechanism of developmental regression in ASD. About one-third of young
children with ASD lose some skills during the preschool period, usually speech,
but sometimes also nonverbal communication, social or play skills are also
affected. There is a lot of evidence suggesting that most children who
demonstrate regression also had previous, subtle, developmental differences. It
is difficult to predict the prognosis of autistic children with developmental
regression. It seems that the earlier development of social, language, and
attachment behaviors followed by regression does not predict the later recovery
of skills or better developmental outcomes. The underlying mechanisms that lead
to regression in autism are unknown. The role of subclinical epilepsy in the
developmental regression of children with autism remains unclear.
PMID- 27493418
TI - The results of different diagnostic imaging studies used in children with urinary
tract infection.
AB - Urinary tract infections (UTI) can cause significant renal scarring, which can be
complicated by hypertension and renal impairment. This study describes the
outcome of different imaging modalities in children with UTI and its relation to
age, sex and type of UTI. Our objective was to describe the frequencies of
different imaging studies, which were used to investigate children with UTI at
King Fahad Hospital (KFH) between the years 2003 and 2008. This is a descriptive
study of all children presenting with UTI at KFH from 2003 to 2008. The study
population, 100 children , were divided into 3 age groups; first group (> 1 month
to 2 years); second group (> 2 to 5 years) , third group (> 5 to 12 years). All
enrolled children were confirmed to have had UTI via urinary cultures. Ninety
seven (97%) patients underwent renal ultrasonography (US), 77 (77%) had a 99mTc
dimercaptosuccinic acid (DMSA) scan within 2 months of presentation, and 60 (60%)
patients underwent micturating cystourethrogram (MCUG), mainly those with an
abnormal DMSA scan. A total of 100 patients screened, 10 (10%) were males and 90
(90%) were females, first age group constituted 10%, second age group was 25% ,
third age groups was 65%. E-coli was isolated in 84% of patients, 60% had
recurrent UTI, 45% had pyelonephritis, 48.4% had abnormal renal US, 61% had an
abnormal DMSA scan, and 26.6% had abnormal MCUG. UTI can cause significant
morbidity in children if not managed properly. Imaging studies are useful in
identifying children who require advanced medical intervention; however, such
studies should be performed only when indicated.
PMID- 27493419
TI - Zinc supplementation for the treatment of severe pneumonia in hospitalized
children: A randomized controlled trial.
AB - The objectives of this randomized controlled trial (RCT) were to compare the mean
duration of hospital stay and mean time to relieve severe pneumonia signs and
symptoms with or without zinc supplementation in hospitalized young children.
This RCT was conducted from Oct 2011 to Mar 2012. in the paediatric department,
PGM/Lahore General Hospital. Three hundred children (150 in each group) were
randomly allocated to two groups: group A received zinc syrup (20 mg/day q 12
hourly) till discharge and group B received placebo syrup. This in addition to
the antibiotic treatment. Data for severe pneumonia signs and symptoms i.e.
oxygen saturation, respiratory rate, temperature and chest indrawing were
recorded. The mean age of participants was 16.65+4.23 months in Group-A
and15.96+5.11 months in Group-B. We found that the mean duration to relieve
severe pneumonia signs and symptoms was 44.62+2.56 hours in Group-A and
48.73+3.124 hours in Group-B (p-value 0.023).Duration of hospital stay was
128.31+3.71 hours in Group-A and 137.67+2.56 in Group-B (p-value 0.001). We
conclude that zinc supplementation for the treatment of children with pneumonia
is an effective therapy along with standard treatment.
PMID- 27493420
TI - Spectrum of attention deficit hyperactivity disorders (ADHD) among Sudanese
children with epilepsy.
AB - Epilepsy is commonly encountered in children with attention deficit hyperactivity
disorder (ADHD). This study aims to determine the spectrum of ADHD among Sudanese
children with epilepsy. The study was conducted at the Epilepsy and
Neurodisabilities Outpatient Clinic for Children at Saad Abu Elila University
Hospital, Khartoum, Sudan during the period January - July 2013. All patients
with epilepsy who presented to the clinic during the study period were assessed
for ADHD using psychometric questionnaire. According to the interpretation guide,
the degree of probability of ADHD was identified. Out of 720 patients with
epilepsy 77(10.6%) were identified as having ADHD. Of these 50 (19.50%) patients
had a high probability of having ADHD, 29 (37.70%) above average, 29 (37.70%)
average and 4 (5.20%) had low ADHD spectrum.
PMID- 27493421
TI - Evaluation of quality of routine physical examination in urban public basic
schools in Khartoum State, Sudan.
AB - The objectives of this study are to identify the availability of the service
logistics in basic public schools (structure as quality concept), to assess steps
of physical examination according to the ministry of health guidelines (process
as quality concept) and to measure satisfaction of service consumers (pupils) and
service providers (teacher and doctors). The study involved seven localities in
Sudan using questionnaires and observations. The structure in form of material
and human resources was not well maintained, equally the process and procedure of
medical examination did not well fit with rules of quality, however, the
satisfaction level was within the accepted level. As far as structure, process
and outcome were concerned, we are still below the standards in developed
countries for many reasons but the level of satisfaction in the present study is
more or less similar as in else studies.
PMID- 27493422
TI - Familial hemophagocytic lymphohistiocytosis in two Saudi siblings.
AB - Primary familial hemophagocytic lymphohistiocytosis (HLH; or familial
erythrophagocytic lymphohistiocytosis [FEL]) is a heterogeneous autosomal
recessive disorder more prevalent with parental consanguinity. There is
aggressive proliferation of activated macrophages and histiocytes, which
phagocytose red blood cells (RBCs), white blood cells (WBCs), and platelets,
leading to anemia, neutropenia and thrombocytopenia. The exaggerated response of
immune system in familial HLH can occur in the absence of infection. We report on
two Saudi siblings with familial hemophagocytic lymphohistiocytosis. The first
case was diagnosed and started on treatment but died after ten days of treatment
while the second one was referred to a higher centre for treatment but died
before commencing chemotherapy treatment. This rare inherited aggressive disease
needs high index of suspicion and early treatment. Anti-inflammatory therapy
consisting of steroids, etoposide or antithymocyte globulin (ATG), should be
instituted promptly, followed by curative hematopoietic cell transplantation to
get a better outcome. Without treatment, most patients with familial
hemophagocytic lymphohistiocytosis survive only a few months.
PMID- 27493424
TI - The boy who stopped walking....
PMID- 27493423
TI - Infantile cortical hyperostosis - a report of Saudi family.
AB - A 2-weeks-old Saudi neonate was apparently well till the 10th day of life when a
swelling of the right groin was noted accompanied by irritability and fever,
without history of trauma. On examination: the girl was irritable and febrile,
the mass was firm, ill defined, fixed and tender. The state of the underlying
skin was normal. There was family history of 3 siblings with similar swellings in
the neonatal period and one of them had recurrence of the condition till the age
of 7 year. The radiological findings indicated diaphysis hyperostosis, sparring
of the epiphysis and the benign course of the disease. With exclusion of
syphilis, osteomyelitis and trauma, the likely diagnosis would be infantile
cortical hyperostosis. Such diagnosis should not be overlooked when faced by bony
swellings in neonates.
PMID- 27493425
TI - The International Child Neurology Association (ICNA) Educational Meetng in
Khartoum, Sudan.
PMID- 27493426
TI - ICNA meeting: January 27-31, 2015.
PMID- 27493427
TI - The orchestrated performance of the ICNA and first PET1 Course at the confluence
of the Niles: Khartoum, January 2015.
PMID- 27493428
TI - Welcome Speech of the International Child Neurology Association (ICNA)
Educational Meeting in Khartoum, Sudan (January 27-31, 2015).
PMID- 27493429
TI - Lessons to the World: Sudanese Youth and the Wellbeing of Children.
PMID- 27493430
TI - Hawadith Street Initiative: A unique Sudanese childhood charity experience.
AB - Due to escalating conflicts and resultant economic constraints, different social
services in low income and low-middle income countries have witnessed a decline
in its standards, and increase in the costs. This situation has led to emergence
of large numbers of patients and their families who cannot afford the costs of
health services provided by public hospitals. On this background, and the old
heritage of the Sudanese to help the needy, the Hawadith Street Initiative (HSI)
was established. Named after the street on which it was founded - which
translates indirectly to "Accidents Lane", HSI was established in 2012 by a group
of youths, most of them in their twenties of age, and recently graduated. The
main activity of the initiative is helping the needy hospital patients,
especially with regards to their treatment costs, in Khartoum and other cities in
Sudan. Starting with recreational programs for cancer patients, and public
campaigns for donation of blood, the initiative's youths changed their
activities. Using the social media, Facebook, they adopted the strategy of
communication with potential donors, after sending posts containing brief
anonymous presentations and call of help for needy cases. Currently HSI includes
more than 2000 volunteers in Khartoum and 17 other cities. The most important
achievement of HSI is the establishment of an intensive care unit at a children
hospital in Omdurman city costing 435,880 US dollars. HSI demonstrates the
possibility of delivering great services with minimum resources, and constitutes
a unique organization, worldwide, in a new wave of Internet-based initiatives.
PMID- 27493431
TI - Beyond the guidelines of paediatric septic shock: A focused review.
AB - Severe sepsis and septic shock continue to cause major morbidity and mortality
among children, especially in the resource-limited areas. Guidelines that focus
on these entities, such as "Surviving Sepsis" and "Paediatric Advanced Life
Support" guidelines, are revised and updated on regular basis to incorporate new
evidence based medicine. There is ongoing need to review these updated
guidelines, and address potentially best available solutions for adapting them
into suitable practical steps for paediatricians worldwide, especially those
working in resource-limited areas. The available recommendations may help to
improve sepsis management in middle- and low-income countries; however,
guidelines must be wisely implemented according to the available resources, with
follow up auditing to ensure appropriate implementation.
PMID- 27493432
TI - Spinal cord schistosomiasis.
AB - Acute myelopathy is increasingly being recognized as a common neurological
complication of schistosomiasis. Schistosome eggs reach the spinal cord either as
egg emboli or as eggs produced by ectopic worms. This leads to inflammatory
reaction and granuloma formation around the eggs. Patients with spinal
schistosomiasis may not have clinical evidence of schistosomiasis. The typical
clinical picture is that of lumbar pain preceded by other symptoms by hours or up
to 3 weeks. Patients may present with paraparesis, urinary retention or
paraplegia. Definitive diagnosis of spinal cord schistosomiasis is by detection
of the eggs in a spinal cord biopsy or at autopsy. However, most cases are
diagnosed based on a presumptive diagnosis that depends on a suggestive clinical
picture, history or evidence of active schistosomiasis and exclusion of other
conditions. Investigations include stools and urine examination for schistosome
eggs, blood tests, magnetic resonance imaging (MRI) and examination of the
cerebrospinal fluid. Treatment of cases is mainly by praziquantel,
corticosteroids, surgical intervention and rehabilitation.
PMID- 27493433
TI - The prevalence and factors affecting attention deficit hyperactivity disorder
among school children in Khartoum State.
AB - Attention deficit hyperactivity disorder (ADHD) is one of the most common
neurodevelopmental disorders in children, characterized by age-inappropriate
features of inattention, hyperactivity and impulsivity or both. The aim of this
study is to determine the prevalence and socio demographic correlates of ADHD
symptoms in general basic schoolchildren. A cross-sectional study conducted in
Khartoum North. A random sample of 190 general basic schools was chosen, from
which sample of 1000 students from both boys and girls were selected by
systematic random sampling, their age ranges between 7 and 14 years. They were
screened for different subtypes of ADHD symptoms using the SNAP-IV-C teacher and
parent rating scale, which is a revision of the Swanson Nalon and Pelham (SNAP)
questionnaire. The overall prevalence of ADHD was 9.4%. The prevalence of
children with ADHD/inattentive sub type, ADHD/ hyperactive-impulsive sub type,
ADHD/ combined subtype were 3.5%, 6.9 % and 1.0 %, respectively. The prevalence
rate increased significantly with the increase in age. The study showed that the
prevalence of ADHD symptoms among school children in Sudan was high as rated by
both teacher and parents rather than what has been reported in other studies.
ADHD symptoms are more common among boys than girls and more prevalent in late
childhood and in those who lived in rural area.
PMID- 27493434
TI - Evaluation of physicians' knowledge about prevention of rheumatic fever and
rheumatic heart disease before and after a teaching session.
AB - Rheumatic fever (RF) and rheumatic heart disease RHD remain as one of the major
cardiovascular problems in Sudanese children. The cornerstones for control of RF
and RHD are primary and secondary preventions as adopted by Sudan's programme.
This study aimed to describe and raise the paediatric doctors' awareness about
prevention of RF and RHD using lectures. It was a prospective, cross-sectional,
hospital based study, conducted in Khartoum. The study populations were
paediatric doctors including house officers, medical officers and registrars.
Data were collected through self-administered questionnaire, which was
constructed to assess the doctor's awareness about RF and RHD prevention before
and after attending lectures. Eighty seven doctors participated in the study. The
results showed that the overall doctors' awareness about prevention of rheumatic
fever and rheumatic heart disease was at average level. It was raised by
intervention through lectures to good level. It is recommended to introduce
training programs for physicians in order to improve doctors' awareness about
prevention of RF and RHD. Such activities need to be conducted at regular
intervals.
PMID- 27493435
TI - Pediatric pain management: More opportunities for better comfort.
AB - Pediatric pain assessment is vital for optimal pediatric practice. After a year
of implementation of pediatric pain assessment tools at a tertiary university
hospital (King Saud University Medical City, Riyadh, Saudi Arabia), the
physicians in the Department of Pediatrics were invited to participate in an
interactive lecture about pediatric pain management to assess their awareness
about using these tools. Their responses demonstrated that almost half of them
were not using any pain scale in their daily practice. These findings highlight
the need for a new strategy of implementation. The improvement of pain assessment
and management necessitates extensive educational campaign for all health care
providers and early audit in order to improve the physicians' awareness and
compliance with these changes.
PMID- 27493436
TI - Oxygen therapy in neonatal intensive care units in Khartoum State.
AB - Oxygen is a drug that is essential in the treatment and prevention of neonatal
hypoxia. The goal of oxygen therapy is to deliver sufficient oxygen to tissues
while minimizing oxygen toxicity and oxidative stress. Improvement in monitoring
technology of oxygen therapy has helped to improve clinicians' ability to
appropriately apply and deliver oxygen. The objectives of this prospective
observational descriptive hospital based study were: to evaluate the practice of
oxygen therapy in the neonatal intensive care units (NICUs) in Khartoum State, to
identify guidelines of oxygen therapy in NICUs, to determine the mode of oxygen
delivery to the neonates, and to assess the practice of long term follow up of
patients who used oxygen. During the period January - June 2014, 139 neonates
were included. Oxygen was delivered to the neonates in the study depending on the
clinical assessment. Saturation was not measured at the time of oxygen
administration in 119 (85.6%) neonates. Oxygen was delivered by central device in
135 neonates (97.1%). The majority of the staff did not know the practice of long
term follow up. Hundred and sixteen (83.5%) of the nursing staff knew that oxygen
has complications but the majority didn't know the nature of the complications
and what causes them. The study showed that there is lack of guidelines of oxygen
therapy in the NICUs and lack of monitoring procedures, which is important to be
highlighted to overcome the complications and to improve the practice of oxygen
therapy.
PMID- 27493437
TI - Dying for milk: A neonate with severe hypernatremia associated with inadequate
breast feeding.
AB - Inadequate breastfeeding may result in malnutrition, hypernatremic dehydration
and catastrophic outcomes. We describe a case of severe breast feeding associated
hypernatremia which was complicated by acute seizures and severe hyperglycemia.
The baby's condition was initially confused with neonatal diabetes mellitus.
PMID- 27493438
TI - Sturge-Weber syndrome: Continued vigilance is needed.
AB - Sturge-Weber syndrome (SWS) is a non-hereditary congenital disorder due to
somatic mosaic mutations in the GNAQ gene. The classical presentation relates to
the brain lesion (cerebral angiomatous lesion of leptomeninges, which is
responsible for epileptic seizures, hemiparesis and mental retardation), skin
lesion (unilateral facial nevus), ocular and oral involvement. We present a 12
year-old boy who was referred to the Division of Pediatric Neurology, King Saud
University Medical City, Riyadh, Saudi Arabia with left-sided hemiparesis.
Physical examination showed a port wine stain involving the right side of the
face, extending to the upper thorax, and enlargement of both the right eye globe
and cornea (megalocornea), indicating the presence of glaucoma. Following urgent
referral to ophthalmology service, his eye condition improved dramatically post
surgery. Neuroradiological investigations, including cranial computed tomography
(CT) and magnetic resonance angiography (MRI) revealed the classical brain
lesions of SWS, as well as right leptomeningeal choroidal angioma. Ten months
later, he developed focal-onset seizures which responded to treatment. His
cognition is normal with good school performance. Continued vigilance is needed
to identify and manage the complications of SWS.
PMID- 27493439
TI - Approach to a child with recurrent pneumonia.
AB - Pneumonia, or inflammation of the lungs parenchyma associated with consolidation
of alveolar spaces, is a substantial cause of morbidity and mortality in
childhood particularly among children below 5 years of age. It is one of the
common causes of admission to the paediatric ward. The aim of this article is to
provide a guide to a systemic approach for diagnosis and treatment of children
with recurrent pneumonia while not over investigating those with common but
usually unrecognised conditions such as asthma or recurrent simple viral
infections.
PMID- 27493440
TI - Incidental diaphragmatic hernia in an infant with cough.
PMID- 27493441
TI - When history was made in Khartoum Civil Hospital: First introduction of
chemotherapy for schistosomiasis.
AB - John Brian Christopherson (1868-1955) was one of the first doctors to be
recruited to serve in the Sudan under the British colonial rule. During his work
in Sudan (1902-1919) he was key in establishing the civilian medical services in
Sudan, including establishing Khartoum Civil Hospital (opened in 1909). The
present article focuses on the work of Dr Christopherson in Khartoum Civil
Hospital in which he introduced tartar emetic for the first time for the
treatment of schistosomiasis. To validate this treatment, Christopherson
conducted a series of clinical trials and published his findings in leading
medical journals. He had to respond to priority claims over this discovery and to
deal with skepticism about the safety of this new treatment. The publications of
Christopherson covered not only the therapeutic efficacy of the drug but also
discussed the epidemiology of the disease, the possible role of mass chemotherapy
and also envisioned chemotherapy in school-age children as a possible strategy
for future elimination of the disease.
PMID- 27493442
TI - Building Gaafar Ibnauf Children's Hospital: Unprecedented story.
PMID- 27493443
TI - The Editors of Sudanese Journal of Paediatrics would like to thank.
PMID- 27493444
TI - Child and Parent Report of Parenting as Predictors of Substance Use and
Suspensions from School.
AB - This study examined how child and parent reports of parenting were related to
early adolescent substance use and school suspensions. Data were from two time
points six months apart on 321 families with an eighth grade student attending
one of five schools in the Pacific Northwest. Child- and parent-report measures
of family management practices were moderately correlated (r = .29). Child
report, but not parent report, of more positive family management practices
uniquely predicted a lower likelihood of adolescent substance use. Also,
discrepancies between child and parent report of parenting predicted substance
use, with child positive report of family management losing its protective
association with adolescent substance use when parents had negative reports of
their parenting. Parent report, but not child report, of better parenting
predicted lower likelihood of suspensions, suggesting that the salience of child
and parent report may depend on the type of behavioral outcome.
PMID- 27493445
TI - A Multi-Cycle Q-Modulation for Dynamic Optimization of Inductive Links.
AB - This paper presents a new method, called multi-cycle Q-modulation, which can be
used in wireless power transmission (WPT) to modulate the quality factor (Q) of
the receiver (Rx) coil and dynamically optimize the load impedance to maximize
the power transfer efficiency (PTE) in two-coil links. A key advantage of the
proposed method is that it can be easily implemented using off-the-shelf
components without requiring fast switching at or above the carrier frequency,
which is more suitable for integrated circuit design. Moreover, the proposed
technique does not need any sophisticated synchronization between the power
carrier and Q-modulation switching pulses. The multi-cycle Q-modulation is
analyzed theoretically by a lumped circuit model, and verified in simulation and
measurement using an off-the-shelf prototype. Automatic resonance tuning (ART) in
the Rx, combined with multi-cycle Q-modulation helped maximizing PTE of the
inductive link dynamically in the presence of environmental and loading
variations, which can otherwise significantly degrade the PTE in multi-coil
settings. In the prototype conventional 2-coil link, the proposed method
increased the power amplifier (PA) plus inductive link efficiency from 4.8% to
16.5% at (RL = 1 kOmega, d23 = 3 cm), and from 23% to 28.2% at (RL = 100 Omega,
d23 = 3 cm) after 11% change in the resonance capacitance, while delivering 168.1
mW to the load (PDL).
PMID- 27493446
TI - Discovery and Validation of Hypermethylated Markers for Colorectal Cancer.
AB - Colorectal carcinoma (CRC) is one of the most prevalent malignant tumors
worldwide. Screening and early diagnosis are critical for the clinical management
of this disease. DNA methylation changes have been regarded as promising
biomarkers for CRC diagnosis. Here, we map DNA methylation profiling on CRC in
six CRCs and paired normal samples using a 450 K bead array. Further analysis
confirms the methylation status of candidates in two data sets from the Gene
Expression Omnibus. Receiver operating characteristic (ROC) curves are calculated
to determine the diagnostic performances. We identify 1549 differentially
methylated regions (DMRs) showing differences in methylation between CRC and
normal tissue. Two genes (ADD2 and AKR1B1), related to the DMRs, are selected for
further validation. ROC curves show that the areas under the curves of ADD2 and
AKR1B1 are higher than that of SEPT9, which has been clinically used as a
screening biomarker of CRC. Our data suggests that aberrant DNA methylation of
ADD2 and AKR1B1 could be potential screening markers of CRC.
PMID- 27493447
TI - Circulating MicroRNAs as Potential Molecular Biomarkers in Pathophysiological
Evolution of Pregnancy.
AB - MicroRNAs represent nonprotein coding small RNA molecules that are very stable to
degradation and responsible for gene silencing in most eukaryotic cells.
Increased evidence has been accumulating over the years about their potential
value as biomarkers for several diseases. MicroRNAs were predicted to be involved
in nearly all biological processes from development to oncogenesis. In this
review, we address the importance of circulating microRNAs in different
conditions associated with pregnancy starting with the implantation period to
preeclampsia and we shortly describe the correlation between placental
circulating miRNAs and pregnancy status. We also discuss the importance of
microRNAs in recurrent abortion and ectopic pregnancy.
PMID- 27493448
TI - Aqueous Lanthanide Chemistry in Asymmetric Catalysis and Magnetic Resonance
Imaging.
AB - This account describes lanthanide coordination chemistry with a focus on the
similarities between lanthanide complexes used in catalysis and those used as
contrast agents in magnetic resonance imaging.
PMID- 27493449
TI - Generation of Soluble Interleukin-11 and Interleukin-6 Receptors: A Crucial
Function for Proteases during Inflammation.
AB - The cytokines interleukin-11 (IL-11) and IL-6 are important proteins with well
defined pro- and anti-inflammatory functions. They activate intracellular
signaling cascades through a homodimer of the ubiquitously expressed signal
transducing beta-receptor glycoprotein 130 (gp130). Specificity is gained through
the cell- and tissue-specific expression of the nonsignaling IL-11 and IL-6 alpha
receptors (IL-11R and IL-6R), which determine the responsiveness of the cell to
these two cytokines. IL-6 is a rare example, where its soluble receptor (sIL-6R)
has agonistic properties, so that the IL-6/sIL-6R complex is able to activate
cells that are usually not responsive to IL-6 alone (trans-signaling). Recent
evidence suggests that IL-11 can signal via a similar trans-signaling mechanism.
In this review, we highlight similarities and differences in the functions of IL
11 and IL-6. We summarize current knowledge about the generation of the sIL-6R
and sIL-11R by different proteases and discuss possible roles during inflammatory
processes. Finally, we focus on the selective and/or combined inhibition of IL-6
and IL-11 signaling and how this might translate into the clinics.
PMID- 27493450
TI - Evaluation of the Antioxidative, Antibacterial, and Anti-Inflammatory Effects of
the Aloe Fermentation Supernatant Containing Lactobacillus plantarum HM218749.1.
AB - Little work is done to develop Aloe vera (AV) using probiotics. To explore the
potential benefits, the antioxidant effects and the antibacterial effects on
foodborne pathogens of Aloe fermentation supernatant were evaluated in vitro. Our
results indicated that the Aloe fermentation supernatant fermented by
Lactobacillus plantarum HM218749.1 had very strong scavenging capacities of the
DPPH (86%), O2 (*-) (85%), (*)OH (76%), and Fe(2+) chelation (82%) and reducing
powers (242.5 mg/L), and the inhibition zones for Salmonella typhimurium,
Salmonella enteritidis, Shigella flexneri, Escherichia coli, Listeria
monocytogenes, S. dysenteriae 301, Staphylococcus aureus Cowan1, and
Propionibacterium acnes were 16, 15, 19, 20, 21, 20, and 27 mm. Moreover, the low
concentration of Aloe fermentation supernatant had significantly reduced the
production of IL-1beta, TNF-alpha, and IL-6 in both mRNA and protein levels (P <
0.01). Therefore, the Aloe fermentation supernatant can be used as functional
beverage or cosmetic ingredients to guard human intestinal health, delaying
senescence, and prevent chronic diseases.
PMID- 27493451
TI - Inflammation Thread Runs across Medical Laboratory Specialities.
AB - We work on the assumption that four major specialities or sectors of medical
laboratory assays, comprising clinical chemistry, haematology, immunology, and
microbiology, embraced by genome sequencing techniques, are routinely in use.
Medical laboratory markers for inflammation serve as model: they are allotted to
most fields of medical lab assays including genomics. Incessant coding of assays
aligns each of them in the long lists of big data. As exemplified with the
complement gene family, containing C2, C3, C8A, C8B, CFH, CFI, and ITGB2,
heritability patterns/risk factors associated with diseases with genetic glitch
of complement components are unfolding. The C4 component serum levels depend on
sufficient vitamin D whilst low vitamin D is inversely related to IgG1, IgA, and
C3 linking vitamin sufficiency to innate immunity. Whole genome sequencing of
microbial organisms may distinguish virulent from nonvirulent and antibiotic
resistant from nonresistant varieties of the same species and thus can be listed
in personal big data banks including microbiological pathology; the big data
warehouse continues to grow.
PMID- 27493453
TI - The Mystique of Brain Death.
PMID- 27493452
TI - Circulating (CD3(-)CD19(+)CD20(-)IgD(-)CD27(high)CD38(high)) Plasmablasts: A
Promising Cellular Biomarker for Immune Activity for Anti-PLA2R1 Related
Membranous Nephropathy?
AB - Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly
mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The
adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX),
efficacy is still needed to improve clinical outcome of patient with MN. We
evaluated the modification of plasmablasts (CD3(-)CD19(+)CD20(-)IgD(
)CD27(high)CD38(high)), a useful biomarker of RTX response in other autoimmune
diseases, and memory (CD3(-)CD19(+)CD20(+)IgD(-)CD27(+)CD38(-)) and naive (CD3(
)CD19(+)CD20(+)IgD(+)CD27(-)CD38(low)) B cells by fluorescence-activated cell
sorter analysis in PLA2R1 related MN in one patient during the 4 years of follow
up after RTX. RTX induced complete disappearance of CD19(+) B cells,
plasmablasts, and memory B cells as soon as day 15. Despite severe CD19(+)
lymphopenia, plasmablasts and memory B cells reemerged early before naive B cells
(days 45, 90, and 120, resp.). During the follow-up, plasmablasts decreased more
rapidly than memory B cells but still remained elevated as compared to day 0 of
RTX. Concomitantly, anti-PLA2R1 Ab increased progressively. Our single case
report suggests that, besides monitoring of serum anti-PLA2R1 Ab level,
enumeration of circulating plasmablasts and memory B cells represents an
attractive and complementary tool to assess immunological activity and efficacy
of RTX induced B cells depletion in anti-PLA2R1 Ab related MN.
PMID- 27493454
TI - Why are we Poor Organ Donors: A Survey Focusing on Attitudes of the Lay Public
From Northern India.
AB - BACKGROUND: Knowledge, sociocultural views, and awareness about organ donation in
the general population are important for the success of deceased organ donation.
There is an urgent need to gather this information in order to find out the
reasons for poor organ donation rates in India. METHODS: A 30-item questionnaire
was designed in the English and Hindi language and was administered to the lay
people in order to assess their knowledge, views, and attitude regarding brain
death and organ donation. RESULTS: Three hundred and fifty-two people
(male:female = 202:150; mean age = 30.6 +/- 13.9 years) completed the
questionnaire. Only 70% of the people were aware that the organs can be donated
after brain death and only 44% thought that they understood the meaning of brain
death. Media and Internet were the preferred sources for seeking information on
brain death and organ donation. The majority of people (81.2%) were willing to
donate organs after brain death but only 1.4% had registered for organ donation.
Lack of awareness (80.1%), religious beliefs and superstitions (63.4%), and lack
of faith in the healthcare system (40.3%) were believed to be the most important
reasons for poor deceased organ donation rates in India. The survey also
highlighted the importance of the opinion of family members and the religious
leaders in making the decision for organ donation. Educational qualification
above matriculation was significantly associated with the knowledge of brain
death and the willingness for organ donation. CONCLUSION: Lack of awareness
appears to be the most important factor for low donation rates in India.
Educating people by using media and Internet and conducting awareness programs
may help in improving the donation rates.
PMID- 27493456
TI - Long-Term Outcomes of Liver Transplantation for Hepatic Sarcoidosis: A Single
Center Experience.
AB - AIM: Hepatic sarcoidosis is a rare indication for orthotopic liver
transplantation (OLT). Hence, studies evaluating these patients are scarce. We
present a single center experience with OLT for hepatic sarcoidosis in a case
control study. METHODS: A retrospective chart review was performed on 970
patients with OLT at our center, and 13 patients (1.3%) were identified who
underwent 14 OLTs for hepatic sarcoidosis. For each case, two controls matched
for etiology of liver disease, recipient age (+/-5 years), and duration since
transplant (within 5 years) were selected. RESULTS: For the 13 patients
transplanted for sarcoidosis, the median age was 46 years. The majority were
women (62%) and African-American (85%). Cholestatic liver disease was the primary
manifestation. Portal hypertensive complications were present in 11 patients
(84%). The median MELD score at transplantation was 19. Extra-hepatic
manifestations were present in ten patients (77%). All patients received whole
deceased 14 donor allografts. Six patients remain alive with a median post-OLT
follow-up of 8.4 years. The 1-, 3-, 5-, and 10-year patient survival rates were
84.6%, 76.9%, 61.1%, and 51.3%, respectively for the sarcoidosis group and 82.1%,
78.6%, 78.6%, and 61.9%, respectively for the matched PSC/PBC group (P = 0.739).
Re-graft free survival for sarcoidosis patients was 84.6%, 76.9%, 61.5%, and
51.3% for 1-, 3-, 5-, and 10-years and for the matched control group re-graft
free survival was 78.6% at 1-, 3-, 5-years, and 64.8% at 10-years (P = 0.661).
Recurrence of hepatic sarcoidosis was found in 4 patients at 11 days, 112 days,
222 days, and 6.6 years. CONCLUSIONS: Our study depicts the long-term benefit of
liver transplantation in patients with end stage liver disease secondary to
sarcoidosis. It shows statistically comparable graft and patient survival for
such patients when compared to other cholestatic diseases. Disease recurrence,
although possible, has not been shown to cause allograft dysfunction.
PMID- 27493455
TI - Addition of Dexamethasone Alters the Bile Acid Composition by Inducing CYP8B1 in
Primary Cultures of Human Hepatocytes.
AB - BACKGROUND: Primary human hepatocytes offer the best human in vitro model for
studies on human liver cell metabolism. Investigators use a variety of different
media supplements and matrix biocoatings and the type of culture system used may
influence the outcome. OBJECTIVES: To optimize in vitro conditions for primary
human hepatocytes with regard to bile acid synthesis. METHODS: Human hepatocytes
were isolated and cultured on collagen type I or EHS matrigel in cell media with
or without dexamethasone. The glucocorticoid receptor (GR) antagonist RU486 was
used to elucidate the involvement of GR. RESULTS: Hepatocytes cultured on EHS
matrigel produced more bile acids and expressed higher levels of cholesterol
7alpha-hydroxylase (CYP7A1) than cells cultured on rat tail collagen.
Supplementation with dexamethasone increased the formation of cholic acid (CA)
and decreased chenodeoxycholic acid formation. In line with these results, the
mRNA expression of sterol 12alpha-hydroxylase (CYP8B1) increased following
dexamethasone treatment. Surprisingly, the mRNA expression of CYP7A1 and CYP27A1
was not increased to the same extent. By using the GR antagonist RU486, we
concluded that CYP8B1 induction is mediated via a GR-independent pathway. An
altered expression of retinoid-related orphan receptor (ROR) alpha and ROR alpha
target gene Glucose-6-phosphatase (G6Pase) suggests that ROR alpha signaling may
regulate CYP8B1 expression. CONCLUSION: Primary human hepatocytes have an
increased bile acid synthesis rate when cultured on matrigel as compared to
collagen. Exposure to glucocorticoid hormones stimulates the expression of
CYP8B1, leading to an increased formation of CA and alteration of the bile acid
composition. The effect is most likely mediated through a GR-independent pathway,
possibly through ROR alpha.
PMID- 27493457
TI - Limited Fibrosis Progression but Significant Mortality in Patients Ineligible for
Interferon-Based Hepatitis C Therapy.
AB - BACKGROUND: Individuals ineligible for interferon-based hepatitis C therapy may
have a worse prognosis than patients who have failed or not received treatment.
AIMS: To provide information about the limitations of medical treatment of
hepatitis C in real-world patients. METHODS: We studied 969 treatment-ineligible
patients and 403 treated patients enrolled between 1/1/01 and 6/30/06; data were
collected until 3/31/13. Treatment barriers were grouped into five categories and
classified as health-related or health-unrelated. Fibrosis stage was assessed
initially and at the end of follow-up. Mortality was determined by search of the
Social Security database. Death certificates of treatment-ineligible patients
were reviewed. RESULTS: Initially, 288 individuals had advanced fibrosis and
compensated disease; 87 untreated patients developed advanced fibrosis during
follow-up. Health-related treatment barriers were more commonly associated with
fibrosis progression and worse survival. During follow-up, 247 untreated patients
died: 47% of liver-related and 53% of liver-unrelated causes. Patients with
significant comorbid illness had the worst five- (70%) and ten-year (50.5%)
survival. Despite high mortality (47%) in persons with decompensated liver
disease, no treatment barrier was associated with a greater incidence of liver
related death. Only significant comorbid medical illness was an independent
predictor of disease progression; however, it was not associated with a greater
incidence of liver-related death. Furthermore, treated patients had better 10
year survival than untreated patients on Kaplan-Meier analysis (80.3% vs. 74.5%,
P = 0.005). CONCLUSION: Many patients with hepatitis C will die of non-liver
related causes and may not be helped by anti-viral treatment.
PMID- 27493458
TI - Donor Factors Including Donor Risk Index Predict Fibrosis Progression, Allograft
Loss, and Patient Survival following Liver Transplantation for Hepatitis C Virus.
AB - BACKGROUND: The utilization of liver transplantation (LT) is limited by the
availability of suitable organs. This study aimed to assess the impact of the
donor risk index (DRI) and other donor characteristics on fibrosis progression,
graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients.
METHODS: HCV-infected LT recipients who had at least 2 post-LT protocol liver
biopsy specimens available were included. Hazard ratio for bivariate analysis was
computed using Cox proportional hazard regression analysis. RESULTS: Of 312
recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5
67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure
was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was
significantly associated with patient and graft survival (P = 0.04). Of the
subset of 104 individuals who underwent histological analysis, 67.3% progressed
to >=F2. On multivariate analysis, significant donor-specific predictors of
fibrosis progression were: donor age >50 years and DRI >1.7. CONCLUSIONS: (1)
Fibrosis progression in HCV-infected LT recipients is strongly associated with
donor characteristics, specifically donor age and DRI. (2) DRI, an objective
measure of donor quality, appears to correlate both with rate of histological
progression and overall patient/graft survival.
PMID- 27493459
TI - Anti-HBc Screening of Blood Donors in Bangladesh: Relevance to Containment of HBV
Propagation.
AB - OBJECTIVES: To avoid further transmission of hepatitis B virus (HBV) infection,
blood is tested for hepatitis B surface antigen (HBsAg) before transfusion.
However, post-transfusion hepatitis B has been detected in clinics after
transfusion of HBsAg-negative blood. The study presented here was undertaken to
assess if HBsAg-negative blood is free from HBV or not. METHODS: Sera were
collected from 398 blood donors who were negative for HBsAg. Out of 398 blood
samples, antibody to hepatitis B core antigen (ant-HBc) was detected in 82 sera
samples. HBV DNA was evaluated in HBsAg-negative, anti-HBc-positive sera. HBsAg,
hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe), and anti-HBc in the
sera were measured by an enzyme-linked immunosorbent assay (ELISA). HBV DNA was
quantified by a real time polymerase chain reaction (PCR). RESULTS: Out of 82
HBsAg-negative, anti-HBc-positive sera samples, HBV DNA were detected in the sera
of 7 voluntary blood donors. Out of these 7 subjects, all were negative for
HBeAg. The levels of ALT were more than 30 IU/L in 6 of 7 HBVDNA-positive
subjects and it was above upper limit of normal (>42 IU/ml) in one subject.
CONCLUSIONS: The present recommendation about blood transfusion of HBsAg-negative
blood system is not capable of blocking HBV transmission to blood recipients.
Although advanced countries have adopted nucleic acid testing (NAT) for
preventing HBV transmission, developing countries may apply anti-HBc testing and
ALT estimation before blood transmission.
PMID- 27493461
TI - A Rare Presentation of Leishmaniasis.
AB - Leishmaniasis or kala-azar is a protozoan disease that can present as cutaneous,
mucocutaneous, visceral, and disseminated disease. In India, it is usually
localized in distinct areas of Bihar, Jharkhand, West Bengal, and parts of
Eastern Uttar Pradesh. Visceral leishmaniasis (VL) involves the visceral organs,
mainly the liver, the spleen and bone marrow. VL is characterized by prolonged
fever, massive splenomegaly, weight loss, progressive anemia, pancytopenia, and
hypergammaglobulinemia, and can be complicated by serious infections. In most of
the patient the diagnosis is made on bone marrow biopsy or splenic aspirate. We
hereby present an unusual case of kala-azar in a 52-year-old patient non-resident
of endemic area presenting with pyrexia of unknown origin, in whom bone marrow
biopsy was negative for Leishmanin Donovan (LD) bodies, and diagnosis was made by
liver biopsy in which LD bodies were seen.
PMID- 27493462
TI - Innovative Approach of Using Esophageal Stent for Refractory Post-Band Ligation
Esophageal Ulcer Bleed Following Living Donor Liver Transplantation.
AB - Bleeding from post-banding esophageal ulcers is uncommon. It is associated with
significant morbidity and mortality. The bleeding from post-banding ulcers is
difficult to manage and may be refractory to endotherapy and pharmacological
treatment; transjugular intrahepatic portosystemic shunt can be used in such
cases. We present a case of refractory post-banding ulcer bleed in a liver
transplant recipient, which was managed by placement of removable esophageal
metal stent.
PMID- 27493463
TI - Unusual Cause of Cholestatic Jaundice in a Young Immunocompetent Male.
PMID- 27493460
TI - Indian National Association for Study of the Liver (INASL) Guidance for Antiviral
Therapy Against HCV Infection: Update 2016.
AB - India contributes significantly to the global burden of HCV. While the nucleoside
NS5B inhibitor sofosbuvir became available in the Indian market in March 2015,
the other directly acting agents (DAAs), Ledipasvir and Daclatasvir, have only
recently become available in the India. The introduction of these DAA in India at
a relatively affordable price has led to great optimism about prospects of cure
for these patients as not only will they provide higher efficacy, but combination
DAAs as all-oral regimen will result in lower side effects than were seen with
pegylated interferon alfa and ribavirin therapy. Availability of these newer DAAs
has necessitated revision of INASL guidelines for the treatment of HCV published
in 2015. Current considerations for the treatment of HCV in India include the
poorer response of genotype 3, nonavailability of many of the DAAs recommended by
other guidelines and the cost of therapy. The availability of combination DAA
therapy has simplified therapy of HCV with decreased reliance of evaluation for
monitoring viral kinetics or drug related side effects.
PMID- 27493464
TI - Hepatocyte Regeneration and Inhibition of Proliferation: Two Sides of a Coin.
PMID- 27493465
TI - Hepatobiliary Quiz Answers - 18 (2016).
PMID- 27493466
TI - Acute Liver Failure Caused by Hepatitis A Virus with Dengue Coinfection.
PMID- 27493467
TI - Use of Barbed Sutures in Laparoscopic Gastrointestinal Single-Layer Sutures.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic anastomotic methods are not commonly used
because of the cumbersome laparoscopic intracorporeal sutures and tying involved.
The barbed suture is one of the various devices developed to simplify the
placement of intracorporeal sutures. However, barbed sutures are not commonly
used during reconstruction after radical gastrectomy in cancer patients or for
single-layer entire-thickness running suturing for intestinal anastomoses. We
describe the procedure for using barbed sutures and report on the short-term
surgical outcomes. METHODS: Between August 2012 and March 2014, 15-cm-long barbed
sutures (V-Loc 180; Covidien, Mansfield, MA, USA) were used for laparoscopic
intestinal anastomoses, including intestinal hole closure for esophagojejunal and
gastrojejunal anastomoses after mechanical anastomoses and gastric wall closure
after partial resection. RESULTS: In total, 38 patients underwent 40 laparoscopic
anastomoses (esophagojejunostomies, 26; gastrojejunostomies, 7; and simple
closure of gastric defect, 7); no cases required conversion to open surgery. Two
cases exhibited positive air leak test results during surgery (1 case of
esophagojejunostomy and 1 case of simple closure of gastric defect). Two cases of
intestinal obstruction were noted; of those, one patient with postoperative
intestinal paresis (grade II) was managed conservatively, and the other underwent
repeat laparoscopic surgery (grade IIIb) for internal herniation unrelated to V
Loc use. No postoperative complications at the anastomosis site and no surgery
related deaths were noted. CONCLUSION: Single-layer entire-thickness running
suturing with the V-Loc 180 barbed suture after stapled side-to-side intestinal
anastomosis was found to be safe and feasible in the reported cases.
PMID- 27493468
TI - Laparoscopic Colorectal Training Gap in Colorectal and Surgical Residents.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic colorectal surgery is an established safe
procedure with demonstrated benefits. Proficiency in this specialty correlates
with the volume of cases. We examined training in this surgical field for both
general surgery and colon and rectal surgery residents to determine whether the
number of cases needed for proficiency is being realized. METHODS: We examined
the Accreditation Council for Graduate Medical Education (ACGME) and American
Board of Colorectal Surgeons (ABCRS) operative statistics for graduating general
surgery and colon and rectal surgery residents. RESULTS: Although the number of
advanced laparoscopy cases had increased for general surgery residents, there was
still a significant gap in case volume between the average number of laparoscopic
colorectal operations performed by graduating general surgery residents (21.6)
and those performed by graduating colon and rectal surgery residents (81.9) in
2014. CONCLUSION: There is a gap between general surgery and colon and rectal
surgery residency training for laparoscopic colorectal surgery. General surgery
residents are not meeting the volume of cases necessary for proficiency in
colorectal surgery. This deficit represents a structural difference in training.
PMID- 27493469
TI - Quality of Communication in Robotic Surgery and Surgical Outcomes.
AB - BACKGROUND AND OBJECTIVES: Robotic surgery has introduced unique challenges to
surgical workflow. The association between quality of communication in robotic
assisted laparoscopic surgery and surgical outcomes was evaluated. METHODS: After
each gynecologic robotic surgery, the team members involved in the surgery
completed a survey regarding the quality of communication. A composite quality-of
communication score was developed using principal component analysis. A higher
composite quality-of-communication score signified poor communication. Objective
parameters, such as operative time and estimated blood loss (EBL), were gathered
from the patient's medical record and correlated with the composite quality-of
communication scores. RESULTS: Forty robotic cases from March through May 2013
were included. Thirty-two participants including surgeons, circulating nurses,
and surgical technicians participated in the study. A higher composite quality-of
communication score was associated with greater EBL (P = .010) and longer
operative time (P = .045), after adjustment for body mass index, prior major
abdominal surgery, and uterine weight. Specifically, for every 1-SD increase in
the perceived lack of communication, there was an additional 51 mL EBL and a 31
min increase in operative time. The most common reasons reported for poor
communication in the operating room were noise level (28/36, 78%) and console-to
bedside communication problems (23/36, 64%). CONCLUSION: Our study demonstrates a
significant association between poor intraoperative team communication and worse
surgical outcomes in robotic gynecologic surgery. Employing strategies to
decrease extraneous room noise, improve console-to-bedside communication and team
training may have a positive impact on communication and related surgical
outcomes.
PMID- 27493470
TI - Robotic Trachelectomy After Supracervical Hysterectomy for Benign Gynecologic
Disease.
AB - BACKGROUND AND OBJECTIVES: A renewed interest in the supra cervical approach to
hysterectomy has created a cohort of patients with a retained cervix at risk of
persistent symptoms requiring a subsequent trachelectomy. The objective of this
study was to evaluate the efficacy of robotic trachelectomy after a previous
supracervical hysterectomy. METHODS: This is a retrospective chart review of
women who had robotic trachelectomy after supracervical hysterectomy for benign
gynecologic disease from January 2009 through October 2014. RESULTS: Eleven
patients underwent robotic trachelectomy for benign conditions during the
observed period. Prior supracervical hysterectomy had been performed for pelvic
pain (8/11, 73%), abnormal uterine bleeding (7/11, 64%), and dysmenorrhea (5/11,
45%). In 10 of 11 patients, the symptoms leading to robotic trachelectomy were
the same as those leading to supracervical hysterectomy. The time from
hysterectomy to recurrence of symptoms ranged from 0.5 to 26 months (median, 6),
whereas the time interval from previous surgery to robotic trachelectomy ranged
from 1 to 57 months (median, 26). Mean age and body mass index at robotic
trachelectomy were 42 +/- 5.4 years and 32 +/- 6.1 kg/m(2). Mean length of
surgery was 218 +/- 88 minutes (range, 100-405). There was 1 major postoperative
complication involving bladder perforation and subsequent vesicovaginal fistula
(VVF). Endometriosis was seen in 27% of pathologic specimens and cervicitis in
another 27%; 45% showed normal tissue histology. In 6 (55%) cases, symptoms
leading to trachelectomy resolved completely after surgery, and the other 5 (45%)
patients reported a significant improvement. CONCLUSIONS: Although trachelectomy
can be a challenging surgery, our experience suggests that the robotic approach
may be a valuable means of achieving safe and reproducible outcomes.
PMID- 27493471
TI - Laparoscopic Total Extraperitoneal Hernia Repair Outcomes.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic inguinal hernia repair has become
increasingly popular as an alternative to open surgery. The purpose of this study
was to evaluate the safety and effectiveness of the laparoscopic total
extraperitoneal procedure with the use of staple fixation and polypropylene mesh.
METHODS: A retrospective chart review examined outcomes of 1240 laparoscopic
hernia operations in 783 patients, focusing on intraoperative and early
postoperative complications, pain, and time until return to work and normal
physical activities. RESULTS: There were no intraoperative complications in this
series; 106 patients experienced early postoperative complications across 8
evaluated categories: urinary retention (4.1%), seroma (3.0%),
testicular/hemiscrotal swelling (1.9%), testicular atrophy (0%), hydrocele
(0.6%), mesh infection (0.1%), and neurological symptoms (transient, 1.0%;
persistent, 0.2%). Patients used an average of 5.6 Percocet pills after the
procedure, and mean times until return to work and normal activities, including
their routine exercise regimen, were 3.0 and 3.8 days, respectively. CONCLUSION:
Complication rates and convalescence times were considered equivalent or superior
to those found in other studies assessing both laparoscopic and open techniques.
The usage of multiple Endostaples did not result in increased neurologic
complications in the early postoperative period when compared with findings in
the literature. In the hands of an experienced surgeon, total extraperitoneal
repair is a safe, effective alternative to open inguinal hernia repair.
PMID- 27493472
TI - Students' Interest in Surgery Affects Laparoscopic Practicing Performance.
AB - BACKGROUND AND OBJECTIVE: Earlier exposure to laparoscopic techniques is thought
to be beneficial for medical students. Reports have demonstrated that practice
improves performance in laparoscopies. In this study, we intended to evaluate
whether medical students' interest in surgery is affected by the amount of
practice and the performance on a laparoscopic simulator. METHODS: A laparoscopic
simulation curriculum was introduced at Taipei Medical University, Wan-Fang
Medical Center. Study participants included 36 sixth-year and 14 seventh-year
students who were divided according to whether they had indicated an interest
(group A) or not (group B) in surgery. The students had twice-a-week practice
sessions for 2 weeks. They underwent baseline measurement (BM) before training
and posttraining measurement (PTM). Self-guided practice on the simulator was
allowed. The learning outcomes were assessed comparing the BM and PTM scores by
using the interquartile range (IQR) test. We also tested the correlation between
total score and number of self-guided practice sessions. RESULTS: All study
participants showed improvement. No differences were observed between BM and PTM
scores and between 6th- and 7th-year medical students. Significant differences
were found in PTM scores between groups A and B (P < .001). Analysis of variance
with a post hoc test for different groups revealed that the PTMs were
significantly higher for both the 6th- and 7th-year medical students in group A
than for those in group B (P < .001). Total performance scores were improved with
a higher number of self-guided practice sessions. Linear regression analysis
demonstrated a significant correlation between the number of self-guided practice
sessions and total performance score (P < .001). CONCLUSION: Those clerks and
interns interested in surgery who had more sessions for self-guided practice,
displayed more improvement than those not interested in surgery did. Improvement
in performance correlated highly with trainees' number of self-guided practice
sessions.
PMID- 27493473
TI - Safety and Efficacy of Polymeric Clips for Appendiceal Stump Closure.
AB - BACKGROUND AND OBJECTIVES: Laparoscopic appendectomy remains one of the most
common emergency general surgical procedures in the United States. In an era of
increasing focus on costs in medical care, we sought to evaluate the use of
polymeric clips to secure the appendiceal base during laparoscopic appendectomy.
METHODS: We performed a prospective cohort study of patients undergoing
laparoscopic appendectomy from April 2013 through September 2014 at a single
academic teaching institution. Polymeric clips were used to secure the
appendiceal stump. Tissue dissection techniques and control of the mesoappendix
were the operating surgeon's choice. Clinical outcomes are reported. RESULTS: A
total of 25 patients (56% women; mean age, 41 y; body mass index of 29 kg/m(2))
were enrolled in our study and underwent laparoscopic appendectomy with polymeric
clips. One patient was unable to have polymeric clips placed due to inflammation
of the appendiceal base. There were no major perioperative complications. One
patient developed a suture abscess in the umbilical incision, and another had
prolonged ileus with computed tomography demonstrating persistent pelvic fluid
that did not require intervention. Median length of stay was 1 d and mean length
of follow-up was 81 d. The use of polymeric clips contributed ~ $32 to the
overall operative cost. CONCLUSIONS: Polymeric clips are a safe alternative for
securing the appendiceal base in laparoscopic appendectomy. They offer
significant cost savings without any evidence of increased complications.
PMID- 27493474
TI - Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in
Human Aortic Valve.
AB - RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification
and quantification of different types of tissues and cells in many organisms.
Although numerous RNA-seq data derived from many types of human tissues and cell
lines, little is known on the transcriptome repertoire of human aortic valve. In
this study, we sequenced the total RNA prepared from two calcified human aortic
valves and reported the whole transcriptome of human aortic valve. Integrating
RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a
transcriptome repertoire of human tissues, including 19,505 protein-coding genes
and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs
were identified as novel noncoding transcripts in our data. By comparing
transcriptome data among different human tissues, we observed substantial tissue
specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human
aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were
more likely to be recently derived from repetitive elements in the primate
lineage, but were less likely to be conserved at the nucleotide level. Expression
profiling analysis showed significant lower expression levels of aortic valve
specific protein-coding genes and lincRNA genes, when compared with genes that
were universally expressed in various tissues. Isoform-level expression analysis
also showed that a majority of mRNA genes had a major isoform expressed in the
human aortic valve. To our knowledge, this is the first comparative transcriptome
analysis between human aortic valve and other human tissues. Our results are
helpful to understand the transcriptome diversity of human tissues and the
underlying mechanisms that drive tissue specificity of protein-coding genes and
lincRNAs in human aortic valve.
PMID- 27493476
TI - Quality Improvement in Critical Care: Selection and Development of Quality
Indicators.
AB - Background. Caring for critically ill patients is complex and resource intensive.
An approach to monitor and compare the function of different intensive care units
(ICUs) is needed to optimize outcomes for patients and the health system as a
whole. Objective. To develop and implement quality indicators for comparing ICU
characteristics and performance within and between ICUs and regions over time.
Methods. Canadian jurisdictions with established ICU clinical databases were
invited to participate in an iterative series of face-to-face meetings,
teleconferences, and web conferences. Eighteen adult intensive care units across
14 hospitals and 5 provinces participated in the process. Results. Six domains of
ICU function were identified: safe, timely, efficient, effective, patient/family
satisfaction, and staff work life. Detailed operational definitions were
developed for 22 quality indicators. The feasibility was demonstrated with the
collection of 3.5 years of data. Statistical process control charts and graphs of
composite measures were used for data display and comparisons. Medical and
nursing leaders as well as administrators found the system to be an improvement
over prior methods. Conclusions. Our process resulted in the selection and
development of 22 indicators representing 6 domains of ICU function. We have
demonstrated the feasibility of such a reporting system. This type of reporting
system will demonstrate variation between units and jurisdictions to help
identify and prioritize improvement efforts.
PMID- 27493477
TI - Who Needs to Be Allocated in ICU after Thoracic Surgery? An Observational Study.
AB - Background. The effective use of ICU care after lung resections has not been
completely studied. The aims of this study were to identify predictive factors
for effective use of ICU admission after lung resection and to develop a risk
composite measure to predict its effective use. Methods. 120 adult patients
undergoing elective lung resection were enrolled in an observational prospective
cohort study. Preoperative evaluation and intraoperative assessment were
recorded. In the postoperative period, patients were stratified into two groups
according to the effective and ineffective use of ICU. The use of ICU care was
considered effective if a patient experienced one or more of the following:
maintenance of controlled ventilation or reintubation; acute respiratory failure;
hemodynamic instability or shock; and presence of intraoperative or
postanesthesia complications. Results. Thirty patients met the criteria for
effective use of ICU care. Logistic regression analysis identified three
independent predictors of effective use of ICU care: surgery for bronchiectasis,
pneumonectomy, and age >= 57 years. In the absence of any predictors the risk of
effective need of ICU care was 6%. Risk increased to 25-30%, 66-71%, and 93% with
the presence of one, two, or three predictors, respectively. Conclusion. ICU care
is not routinely necessary for all patients undergoing lung resection.
PMID- 27493475
TI - Computational Identification of Novel Genes: Current and Future Perspectives.
AB - While it has long been thought that all genomic novelties are derived from the
existing material, many genes lacking homology to known genes were found in
recent genome projects. Some of these novel genes were proposed to have evolved
de novo, ie, out of noncoding sequences, whereas some have been shown to follow a
duplication and divergence process. Their discovery called for an extension of
the historical hypotheses about gene origination. Besides the theoretical
breakthrough, increasing evidence accumulated that novel genes play important
roles in evolutionary processes, including adaptation and speciation events.
Different techniques are available to identify genes and classify them as novel.
Their classification as novel is usually based on their similarity to known
genes, or lack thereof, detected by comparative genomics or against databases.
Computational approaches are further prime methods that can be based on existing
models or leveraging biological evidences from experiments. Identification of
novel genes remains however a challenging task. With the constant software and
technologies updates, no gold standard, and no available benchmark, evaluation
and characterization of genomic novelty is a vibrant field. In this review, the
classical and state-of-the-art tools for gene prediction are introduced. The
current methods for novel gene detection are presented; the methodological
strategies and their limits are discussed along with perspective approaches for
further studies.
PMID- 27493478
TI - The Perception and Estimation of Others' Pain according to Children.
AB - Accurate interpretation of pain expressed by others is important for
socialization; however, the development of this skill in children is still poorly
understood. Empathy for pain models propose two main components (affective and
cognitive), which develop at different stages of life. The study's objective was
to investigate the children's ability between 3 and 12 years of age to detect and
assess the pain intensity in others using visual stimuli depicting either facial
expressions of pain or hands in painful contexts. 40 preschool children and 62
school-aged children were recruited. Children observed series of stimuli and
evaluated the pain intensity depicted. Results demonstrated that children as
young as three years old were able to detect and assess pain in both types of
stimuli and this ability continued to improve until the age of 12. Participants
demonstrated better detection performance with hands than with faces. Results
were coherent with the idea that the two types of stimuli presented recruit
different processes. Pain detection in hands appears to rely mostly on affective
sharing processes that are effective early in life, while older children's higher
ability to perceive pain in facial expressions suggests that this ability is
associated with the gradual development of cognitive processes.
PMID- 27493479
TI - Wnt/Beta-Catenin Signal Inhibitor HC-1 Sensitizes Oral Squamous Cell Carcinoma
Cells to 5-Fluorouracil through Reduction of CD44-Positive Population.
AB - BACKGROUND: Oral squamous cell carcinoma is a prevalent and frequently lethal
malignancy worldwide. Existence of treatment-resistant cancer stem cells is
considered to be associated with tumor formation, recurrence and metastasis.
Wnt/beta-catenin signal is one of the crucial signaling pathways for cancer stem
cells. Wnt/beta-catenin signal inhibitor may reduce the population of cancer stem
cells and improve therapeutic effects on the cancers. METHODS: The effects of
three derivatives of Wnt/beta-catenin signal inhibitors, HC-1, IC-2 and PN3-13,
which we recently developed, on oral squamous cell carcinoma cell line HSC2, were
examined by luciferase reporter assay, WST assay, cell sorting assay and
apoptosis assay. RESULTS: The reporter assay showed that these small molecule
compounds reduced Wnt/beta-catenin transcriptional activity in HSC2 cells. Of
these compounds, IC-2 and PN3-13 inhibited cell viability in a dose-dependent
manner, whereas HC-1 did not at even higher concentrations. Notably, however, the
cell-sorting assay revealed that HC-1 significantly reduces the CD44-positive
population of oral squamous cell carcinoma cells, compared to other compounds
without affecting cell viability. In addition, HC-1 increases the cytotoxicity of
HSC2 cells to 5-fluorouracil. The combination treatment of HC-1 with 5
fluorouracil significantly increased the apoptotic cells whereas treatment by
either compound did not. CONCLUSION: These data suggest that HC-1 is an effective
compound to target cancer stem cells, and the combination treatment of HC-1 and 5
fluorouracil can stimulate the tumor suppressive effect on oral squamous cell
carcinoma cells.
PMID- 27493480
TI - Effect of Gingerol on Cisplatin-Induced Pica Analogous to Emesis Via Modulating
Expressions of Dopamine 2 Receptor, Dopamine Transporter and Tyrosine Hydroxylase
in the Vomiting Model of Rats.
AB - BACKGROUND: Gingerol, the generic term for pungent constituents in ginger, has
been used for treating vomiting in China. We are going to investigate the
mechanisms of inhibitive effect of gingerol on cisplatin-induced pica behaviour
by studying on both peripheral and central levels, and the effects of gingerol on
homeostasis of dopamine (DA) transmission: dopamine D2 receptor (D2R), dopamine
transporter (DAT) and tyrosine hydroxylase (TH). METHODS: The antiemetic effect
of gingerol was investigated on a vomiting model in rats induced by cisplatin 3
mg.kg(-1) intraperitoneal injection (i.p.). Rats were randomly divided into the
normal control group (C), simple gingerol control group (CG), cisplatin control
group (V), cisplatin + metoclopramide group (M), cisplatin + low-dose gingerol
group (GL), cisplatin + middle-dose gingerol group (GM) and cisplatin + high-dose
gingerol group (GH). In observation period, rats in Groups C and V were
pretreated with sterile saline 3 mL i.g.; rats in Group CG were pretreated with
gingerol 40 mg.kg(-1) i.g.; rats in Group M were pretreated with metoclopramide
2.5 mg.kg(-1) i.g.; rats in Groups GL, GM and GH were pretreated with gingerol
10, 20 and 40 mg.kg(-1) i.g. for 3 days, respectively. Cisplatin (3 mg.kg(-1),
i.p.) was administered one time after each treatment with the antiemetic agent or
its vehicle except the Groups C and CG. The distribution of D2R, DAT and TH in
the area postrema and ileum were measured by immunohistochemistry and quantitated
based on the image analysis, and the expression of DAT and TH in the area
postrema and ileum were measured by RT-PCR. The weights of kaolin eaten of the
remaining rats were observed in every 6 h continuously for 72 h. RESULTS: The
weight of kaolin eaten in rats induced by cisplatin was significantly reduced by
pretreatment with gingerol in a dose-dependent manner during the 0-24 h and 24-72
h periods (P < 0.05). Gingerol markedly improved gastric emptying induced by
cisplatin in a dose-dependent manner (P < 0.05), and exhibited effective dose
dependent inhibition on the increase of expression levels of D2R and TH and the
decrease of expression levels of DAT in both the ileum and area postrema (P <
0.05). CONCLUSION: Gingerol is effective on cisplatin-induced emesis in rats
possibly by inhibiting central or peripheral increase of DA by inhibiting D2R, TH
and accelerating DAT.
PMID- 27493481
TI - Pharmacokinetic Interaction Study of Ranitidine and Daijokito in Healthy
Volunteers.
AB - BACKGROUND: Ranitidine is a histamine 2 receptor antagonist, and daijokito is a
Kampo (Chinese herbal medicine as practiced in Japan) formula, which is
traditionally used for treating constipation and digestive trouble. Previous
study demonstrated that daijokito significantly affected the pharmacokinetics of
ranitidine in rats; however, the doses of ranitidine and daijokito in that study
were higher than in clinical practice. Therefore, we examined the pharmacokinetic
interaction between ranitidine and daijokito in clinical practice doses in
healthy volunteers. METHODS: This was a randomized, open label, two-period
crossover study in healthy volunteers (n = 7). Volunteers received
administrations of either a single dose of ranitidine 300 mg, or ranitidine 300
mg in combination with daijokito extract granules 2.5 g. Plasma concentrations of
ranitidine were measured over 12 h by LC/MS/MS method. RESULTS: Plasma
concentrations of ranitidine were lower with co-administration of daijokito
compared with ranitidine alone. Co-administration of daijokito significantly
decreased ranitidine area under the plasma concentration-time curve from 0 to 12
h (AUC0-12) and maximum plasma concentration (Cmax) with geometric mean (GM)
ratio [90% confidence interval (CI)] for AUC0-12 of 0.609 (0.449, 0.826) and Cmax
of 0.515 (0.345, 0.771). CONCLUSION: Co-administration of ranitidine with
daijokito resulted in a significant decrease in plasma level of ranitidine in
healthy volunteers.
PMID- 27493482
TI - Clinical Diagnosis of Mendelian Disorders Using a Comprehensive Gene-Targeted
Panel Test for Next-Generation Sequencing.
AB - BACKGROUND: Genetic diagnoses provide beneficial information to patients and
families. However, traditional genetic diagnoses are often difficult even for
experienced clinicians and require recognition of characteristic patterns of
signs or symptoms to guide targeted genetic testing for the confirmation of
diagnoses. Next-generation sequencing (NGS) is a powerful genetic diagnostic
tool. However, whole-genome and whole-exome sequencing (WES) are expensive, and
the interpretation of results is difficult. Hence, target gene capture sequencing
of gene panels has recently been applied to genetic diagnoses. Herein, we
demonstrate that targeted sequencing approaches using gene panel testing are
highly efficient for the diagnosis of Mendelian disorders. METHODS: NGS using
TruSight one gene panel was performed in 17 families and 20 patients, and we
developed a bioinformatic pipeline at our institution for detecting mutations.
RESULTS: We detected causative mutations in 6 of 17 (35%) families. In
particular, 11 (65%) families had syndromic diagnosis and 6 (35%) had no
syndromic diagnosis before NGS testing. The number of positive diagnoses was 5 of
11 (45%) in the syndromic group and were 1 of 6 (17%) among patients of the no
syndromic diagnosis group. CONCLUSION: Diagnostic yields in the present study
were higher than in previous reports of genetic and chromosomal tests and WES.
The present comprehensive gene-targeted panel test is a powerful diagnostic tool
for Mendelian disorders.
PMID- 27493483
TI - Prion Protein and Stage Specific Embryo Antigen 1 as Selection Markers to Enrich
the Fraction of Murine Embryonic Stem Cell-Derived Cardiomyocytes.
AB - BACKGROUND: The prion protein (PrP) might be useful as a tool to collect cardiac
progenitor cells derived from embryonic stem (ES) cells. It is also possible that
PrP(+) cells include undifferentiated cells with a capacity to develop into
tumors. METHODS: PrP(+) cells isolated from embryoid bodies (EB) formed by mouse
AB1 ES cells were examined using RT-PCR analysis and clonogeneic cell assay. To
assess their potential to differentiate into cardiomyocytes, Nkx2.5(GFP/+)
(hcgp7) cells, another ES cell line that carries the GFP reporter gene in the
Nkx2.5 loci, were used. RESULTS: PrP(+) cells isolated from EB of day 7 and 14
did not express pluripotency markers, but expressed cardiac cell markers, while
PrP(+) cells isolated from EB of day 21 expressed pluripotency markers. Cultured
PrP(+) cells isolated from EB of day 21 expressed pluripotency markers to form
colonies, whereas those isolated from EB of day 7 and 14 did not. To exclude
proliferating cells from PrP(+) cells, stage specific embryo antigen 1 (SSEA1)
was employed as a second marker. PrP(+)/SSEA1(-) cells did not proliferate and
expressed cardiac cell markers, while PrP(+)/SSEA1(+) did proliferate.
CONCLUSION: PrP(+) cells isolated from EB included undifferentiated cells in day
21. PrP(+)/SSEA1(-) cells included cardiomyoctes, suggesting PrP and SSEA1 may be
useful as markers to enrich the fraction of cardiomyocytes.
PMID- 27493484
TI - The First Pilot Comprehensive Evaluation of the Outcomes of Different Types of
Robotic Surgeries in the Different Surgical Departments: The Penta, Tetra and
Trifecta Achievements in Robotic Surgeries.
AB - BACKGROUND: To ensure safe performance in robotic surgery, the Minimal Invasive
Surgery Center (MISC) is composed of the anesthesiology department, five surgery
departments and co-medical staff in our institution. The objective of this study
was to evaluate the outcomes of different types of robotic surgeries for cancer
treatment (n = 326) from different surgery departments in the MISC. METHODS: The
outcomes of robot-assisted radical prostatectomy (RARP), partial nephrectomy
(RAPN), transoral robotic surgery (TORS) for pharyngeal cancer, and robotic
surgery for lung, gastric and rectal cancer were evaluated using the similar
concept of pentafecta in RARP. RESULTS: The pentafecta rates of RARP and robotic
surgery for rectal cancer were 33.3 and 56.5%, respectively. The tetrafecta rates
of RARP (excluding potency evaluation from pentafecta) and TORS were 48.4 and
57.1%, respectively. The trifecta rates of RAPN, robotic surgeries for lung and
gastric cancer were 75.9, 74.2 and 84.2%, respectively. The failure of tetrafecta
in RARP achievement was significantly associated with high risk than with low
risk according to National Comprehensive Cancer Network classification.
CONCLUSION: This is the world's first comprehensive evaluation of different types
of robotic surgeries for cancer treatment in the constitutional framework of an
academic institution. MISC, which provides the constitutional framework of an
academic institution, is providing immeasurable benefits in terms of robotic
surgery quality, and it may ultimately lead to high penta-, tetra-, and trifecta
rates for robotic surgeries for cancer treatment in all surgical departments.
PMID- 27493485
TI - Transurethral En Bloc Resection of Bladder Tumor Using an Endoscopic Submucosal
Dissection Technique: Preliminary Results in an Animal Model.
AB - BACKGROUND: Transurethral resection of bladder tumor (TURBT) technique has been
considered the routine method for removing most bladder tumors for decades. In
contrast, endoscopic submucosal dissection (ESD) is the gold-standard treatment
for gastrointestinal superficial tumors. We investigated the effectiveness and
applicability of a new technique for en bloc bladder tumor resection using ESD
procedure. METHODS: Four Landrace Large White Duroc female pigs were anesthetized
with isoflurane prior endoscopic resection using a large-caliber prototype fiber
bronchoscope. After local infiltration of the submucosa with sodium hyaluronate
using an injector needle, a section of the target area (1.0-2.0 cm diameter
circular area) was cut with the Dual Knife. RESULTS: In total, seven target
sections were resected from the pigs. The median size of the resected sections
was 1.8 cm (range 1.0-2.5 cm) and the median time taken to perform the resection
of one section was 20 min (range 4-35 min). These target sections were completely
resected en bloc. Although the small bladder perforations occurred on two
occasions, no other short-term complications such as uncontrollable bleeding were
observed. CONCLUSION: This procedure is a slightly difficult in the pigs with
thin bladder walls. However, this procedure with the slim flexible cystoscope may
allow us to be able to remove bladder tumors using only light sedation,
especially for cases when small tumor recurrence is observed during routine
cystoscopy for the patients with non-muscle invasive bladder cancer.
PMID- 27493486
TI - Effect of Daisaikoto on Expressions of SIRT1 and NF-kappaB of Diabetic Fatty
Liver Rats Induced by High-Fat Diet and Streptozotocin.
AB - BACKGROUND: Daisaikoto (DSKT), a classical traditional Chinese herbal formula,
has been used for treating digestive diseases for 1800 years in China. Therefore,
in this study, we are going to investigate the effect of DSKT on diabetic fatty
liver rats induced by a high-fat diet and streptozotocin (STZ), and the effects
of DSKT on silent mating type information regulation 2 homolog 1 (SIRT1) and
nuclear factor kappa B (NF-kappaB). METHODS: Diabetic fatty liver rat model was
selected to establish a high-fat diet and STZ. Sixty Wistar rats were divided
into six groups (n = 10): control group, high-fat diet + STZ group, simvastatin
treatment group, DSKT low dose, medial dose and high dose treatment groups. After
8 weeks of drug intervention, body and liver weights, blood chemistry, blood
glucose and insulin were examined. The expressions of sirtuin 1 and NF-kappaB in
the liver were observed by RT-PCR and immunohistochemistry, respectively.
RESULTS: A high-fat diet increased body, liver weights, and serum cholesterol
concentrations. Intraperitoneal injection of STZ increased blood glucose and
decreased body weights. DSKT improved them. Homeostasis model assessment
estimated insulin resistance (HOMA-IR) indices were increased in the high-fat
diet groups. DSKT improved them too. In histological examinations of the liver,
we observed a significant improvement after treatment. Immunostaining expression
of NF-kappaB in the liver was improved by DSKT and simvastatin. The mRNA
expressions of SIRT1 in the liver were increased by DSKT and simvastatin.
CONCLUSION: We have demonstrated that DSKT is capable of reversing dyslipidemia
and insulin resistance induced by a high-fat diet and STZ. High dose DSKT reveals
a stronger effect than simvastatin on the expressions of SIRT1 and NF-kappaB.
Furthermore, DSKT has shown a strong dose-depended protective effect on diabetic
fatty liver.
PMID- 27493487
TI - Recipient Vessel Selection in Head and Neck Reconstruction Based on the Type of
Neck Dissection.
AB - BACKGROUND: Recipient vessel selection in head and neck reconstruction using free
flap transfers has to be standardized. However, the recipient vessel selection
based on the type of neck dissection has yet to be investigated. We describe the
relationship between the type of neck dissection and recipient vessel. METHODS:
Records of 107 consecutive patients who had undergone head and neck
reconstruction using free flap transfers from 2011 to 2015 were reviewed
retrospectively. Ninety-five were men and 12 were women, with a mean age of 65.6
years. Patients were divided into 5 groups based on the type of neck dissection:
no neck dissection (NND, n = 17), upper jugular neck dissection, (UJND, n = 1),
supraomohyoid neck dissection (SOND, n = 18), jugular neck dissection (JND, n =
39), and modified radical neck dissection (mRND, n = 32). We details the number
of recipient vessels we selected for free tissue transfer in head and neck
reconstruction depending on the type of neck dissection. RESULTS: The overall
patency rate was 100%. The superficial temporal artery was used most frequently
in NND; the superior thyroid artery in SOND; the transverse cervical artery in
JND; and the transverse cervical artery in mRND. The superficial temporal vein
was used most frequently in NND; The internal jugular vein in the SOND; and The
external jugular vein in mRND. CONCLUSION: Microsurgeons should remember that
proper recipient vessel selection depending on the type of neck dissection is
important. We believe proper recipient vessel selection should improve results of
head and neck reconstruction using free flap transfer.
PMID- 27493488
TI - Correlation between Ultrasound Findings of Tumor Margin and Clinicopathological
Findings in Patients with Invasive Ductal Carcinoma of the Breast.
AB - BACKGROUND: Breast ultrasound findings regarding tumor margins are crucial in
judging whether a tumor is malignant or benign. However, the relationships
between the margins and clinicopathological characteristics remain largely
unknown. In this study, we examined the clinicopathological characteristics of
patients with invasive ductal carcinoma whose ultrasound images showed either
well-defined and rough or indistinct margins. METHODS: Of all consecutive
patients diagnosed with invasive ductal carcinoma at the Division of Breast and
Endocrine Surgery of Tottori University Hospital from January 2012 to December
2014, 122 patients whose ultrasound images showed either "well-defined and rough"
or "indistinct" tumor margins were included in this study. Mammography and
ultrasound images taken at the initial examination were reviewed. Patients were
divided into two groups based on ultrasound findings of the tumor margins: the
"well-defined and rough group" and the "indistinct group." The relationships
among ultrasound findings, mammography findings and clinicopathological findings
were investigated in the two groups. RESULTS: The well-defined and rough group
was more likely to contain solid-tubular carcinoma, while the indistinct group
was more likely to contain scirrhous carcinoma. The MIB-1 index was higher in the
well-defined and rough group than in the indistinct group. Additionally, the
proportion of patients with nuclear grade 3, estrogen receptor
negative/progesterone receptor-negative, and triple-negative breast cancer was
greater in the well-defined and rough group than in the indistinct group.
CONCLUSION: Invasive ductal carcinomas with well-defined and rough margins on
ultrasound were likely to be malignant and proliferative than those with
indistinct margins.
PMID- 27493489
TI - EEG Power Spectrum Analysis in Children with ADHD.
AB - BACKGROUND: Attention deficit disorder/hyperactivity disorder (ADHD) is a
pathological condition that is not fully understood. In this study, we
investigated electroencephalographic (EEG) power differences between children
with ADHD and healthy control children. METHODS: EEGs were recorded as part of
routine medical care received by 80 children with ADHD aged 4-15 years at the
Department of Pediatric Neurology in Tottori University Hospital. Additionally,
we recorded in 59 control children aged 4-15 years after obtaining informed
consent. Specifically, awake EEG signals were recorded from each child using the
international 10-20 system, and we used ten 3-s epochs on the EEG power spectrum
to calculate the powers of individual EEG frequency bands. RESULTS: The powers of
different EEG bands were significantly higher in the frontal brain region of
those in the ADHD group compared with the control group. In addition, the power
of the beta band in the ADHD group was significantly higher in all brain regions,
except for the occipital region, compared with control children. With regard to
developmental changes, the power of the alpha band in the occipital region showed
an age-dependent decrease in both groups, with slightly lower power in the ADHD
group. Additionally, the intergroup difference decreased in children aged 11
years or older. As with the alpha band in the occipital region, the beta band in
the frontal region showed an age-dependent decrease in both groups. Unlike the
alpha band, the power of the beta band was higher in the ADHD group than in the
control group for children of all ages. CONCLUSION: The observed intergroup
differences in EEG power may provide insight into the brain function of children
with ADHD.
PMID- 27493490
TI - Evaluation of an Hprt-Luciferase Reporter Gene on a Mammalian Artificial
Chromosome in Response to Cytotoxicity.
AB - BACKGROUND: Hypoxanthine guanine phosphoribosyltransferase (Hprt) is known as a
house-keeping gene, and has been used as an internal control for real-time
quantitative RT-PCR and various other methods of gene expression analysis. To
evaluate the Hprt mRNA levels as a reference standard, we engineered a luciferase
reporter driven by a long Hprt promoter and measured its response to
cytotoxicity. METHODS: We constructed a reporter vector that harbored a phiC31
integrase recognition site and a mouse Hprt promoter fused with green-emitting
luciferase (SLG) coding sequence. The Hprt-SLG vector was loaded onto a mouse
artificial chromosome containing a multi-integrase platform using phiC31
integrase in mouse A9 cells. We established three independent clones. RESULTS:
The established cell lines had similar levels of expression of the Hprt-SLG
reporter gene. Hprt-SLG activity increased proportionately under growth
conditions and decreased under cytotoxic conditions after blasticidin or
cisplatin administration. Similar increases and decreases in the SLG luminescent
were observed under growth and cytotoxic conditions, respectively, to those in
the fluorescent obtained using the commercially available reagent, alamarBlue.
CONCLUSION: By employing a reliable and stable expression system in a mammalian
artificial chromosome, the activity of an Hprt-SLG reporter can reflect cell
numbers under cell growth condition and cell viability in the evaluation of
cytotoxic conditions.
PMID- 27493491
TI - Melanoma of the Umbilicus: A Patient Report, Precaution in Operative Strategy,
and the First Histopathological Review of Published Cases.
AB - Umbilical melanoma is extremely rare. Among the past English reports on umbilical
melanoma, there are only 8 reports in which histopathology was described in
detail, and there has been no report with a review of the histopathology of
previously reported cases. We experienced a case of umbilical melanoma and
reviewed previously reported cases including our case. Because of the anatomical
location, it is difficult to become aware of the umbilical melanoma unless there
are some concomitant symptoms such as discharge or swelling. Even with these
symptoms, patients tend to postpone a hospital visit for unknown reasons,
resulting in increased risk of tumor growth and metastasis. When performing
resection of umbilical melanoma, a portion of the peritoneum should also be
removed. Sentinel lymph nodes can be axilla or inguinal lymph nodes. There is a
possibility of metastasis to the preoperative abdominal cavity or to nearby skin
through hematogenous spread. Preoperative evaluation of tumor spread and
postoperative observation are important for umbilical melanoma in order to detect
recurrence or metastasis because of its unique anatomical location.
PMID- 27493492
TI - Mapping of the local environmental changes in proteins by cysteine scanning.
AB - Protein conformational changes, which regulate the activity of proteins, are
induced by the alternation of intramolecular interactions. Therefore, the
detection of the local environmental changes around the key amino acid residues
is essential to understand the activation mechanisms of functional proteins. Here
we developed the methods to scan the local environmental changes using the
vibrational band of cysteine S-H group. We validated the sensitivity of this
method using bathorhodopsin, a photoproduct of rhodopsin trapped at liquid
nitrogen temperature, which undergoes little conformational changes from the dark
state as shown by the X-ray crystallography. The cysteine residues were
individually introduced into 15 positions of Helix III, which contains several
key amino acid residues for the light-induced conformational changes of
rhodopsin. The shifts of S-H stretching modes of these cysteine residues and
native cysteine residues upon the formation of bathorhodopsin were measured by
Fourier transform infrared spectroscopy. While most of cysteine residues
demonstrated no shift of S-H stretching mode, cysteine residues introduced at
positions 117, 118, and 122, which are in the vicinity of the chromophore,
demonstrated the significant changes. The current results are consistent with the
crystal structure of bathorhodopsin, implying that the cysteine scanning is
sensitive enough to detect the tiny conformational changes.
PMID- 27493493
TI - alpha-helix formation rate of oligopeptides at subzero temperatures.
AB - In 1999, Clarke et al. ((1999) Proc. Natl. Acad. Sci. USA 96, 7232-7237) reported
that the nucleation rate of alpha-helix of oligopeptide AK16 is as slow as 60 ms.
In the present study, we measured the nucleation rate of oligopeptide, C17
(DLTDDIMCVKKILDKVG, corresponding to alpha-helical region of 84th to 100th amino
acids of bovine alpha-lactalbumin) using the same method as Clarke et al. We
found only initial bursts of the increase of alpha-helices at temperatures higher
than -50 degrees C in the presence of 70% methanol. The result with AK16 was the
same as Clarke et al. reported. We also found that the folding rate of
polyglutamic acid is too fast to be detected by the stopped-flow apparatus at 4
degrees C. These results demonstrate that the alpha-helix formation rates in C17,
AK16 and polyglutamic acid are shorter than the dead time of the stopped-flow
apparatus (6 ms).
PMID- 27493494
TI - Optimal terminal sequences for continuous or serial isothermal amplification of
dsRNA with norovirus RNA replicase.
AB - The norovirus RNA replicase (NV3D(pol), 56 kDa, single chain monomeric protein)
can amplify double-stranded (ds) RNA isothermally. It will play an alternative
role in the in vitro evolution against traditional Qbeta RNA replicase, which
cannot amplify dsRNA and consists of four subunits, three of which are borrowed
from host E.coli. In order to identify the optimal 3'-terminal sequence of the
RNA template for NV3D(pol), an in vitro selection using the serial transfer was
performed for a random library having the 3'-terminal sequence of ---UUUUUUNNNN
3'. The population landscape on the 4-dimensional sequence space of the 17(th)
round of transfer gave a main peak around ---CAAC-3'. In the preceding studies on
the batch amplification reaction starting from a single-stranded RNA, a template
with 3'-terminal C-stretch was amplified effectively. It was confirmed that in
the batch amplification the ---CCC-3' was much more effective than the ---CAAC
3', but in the serial transfer condition in which the ----CAAC-3' was sustained
stably, the ---CCC-3' was washed out. Based on these results we proposed the
existence of the "shuttle mode" replication of dsRNA. We also proposed the
optimal terminal sequences of RNA for in vitro evolution with NV3D(pol).
PMID- 27493495
TI - Uncovering the mechanism for selective control of the visible and near-IR
absorption bands in bacteriochlorophylls a, b and g.
AB - Bacteriochlorophylls (BChls) play an important role as light harvesters in
photosynthetic bacteria. Interestingly, bacteriochlorophylls (BChls) a, b, and g
selectively tune their visible (Qx) and near IR (Qy) absorption bands by the
substituent changes. In this paper, we theoretically study the mechanism for the
selective control of the absorption bands. Density functional theory (DFT) and
time-dependent DFT (TD-DFT) and four-orbital model analyses reveal that the
selective red-shift of the Qy band with the substituent change from BChl a to b
occurs with the lower-energy shift of the (HOMO, LUMO) excited state directly
induced by the molecular-orbital energy changes. In contrast, the Qx band hardly
shifts by the cancellation between the higher- and lower-energy shifts of the
(HOMO-1, LUMO) excited state directly induced by the molecular-orbital energy
changes and configuration interaction, respectively. On the other hand, with the
substituent changes from BChl a to g, the Qx band selectively blue-shifts by the
larger higher-energy shift of the (HOMO-1, LUMO) excited state directly induced
by the molecular-orbital energy shifts than the lower-energy shift due to the
configuration interaction. In contrast, the Qy band hardly shifts by the
cancellation between the higher- and lower-energy shifts of the (HOMO, LUMO)
excited state directly induced by the molecular-orbital energy changes and
configuration interaction, respectively. Our work provides the important
knowledge for understanding how nature controls the light-absorption properties
of the BChl dyes, which might be also useful for design of porphyrinoid
chromophores.
PMID- 27493496
TI - Effect of the MotB(D33N) mutation on stator assembly and rotation of the proton
driven bacterial flagellar motor.
AB - The bacterial flagellar motor generates torque by converting the energy of proton
translocation through the transmembrane proton channel of the stator complex
formed by MotA and MotB. The MotA/B complex is thought to be anchored to the
peptidoglycan (PG) layer through the PG-binding domain of MotB to act as the
stator. The stator units dynamically associate with and dissociate from the motor
during flagellar motor rotation, and an electrostatic interaction between MotA
and a rotor protein FliG is required for efficient stator assembly. However, the
association and dissociation mechanism of the stator units still remains unclear.
In this study, we analyzed the speed fluctuation of the flagellar motor of
Salmonella enterica wild-type cells carrying a plasmid encoding a nonfunctional
stator complex, MotA/B(D33N), which lost the proton conductivity. The wild-type
motor rotated stably but the motor speed fluctuated considerably when the
expression level of MotA/B(D33N) was relatively high compared to MotA/B. Rapid
accelerations and decelerations were frequently observed. A quantitative analysis
of the speed fluctuation and a model simulation suggested that the MotA/B(D33N)
stator retains the ability to associate with the motor at a low affinity but
dissociates more rapidly than the MotA/B stator. We propose that the stator
dissociation process depends on proton translocation through the proton channel.
PMID- 27493497
TI - Reconstitution of intracellular environments in vitro and in artificial cells.
AB - Toward reconstitution of living cells by artificial cells technology, it is
critical process to understand the differences between mixtures of biomolecules
and living cells. For the aim, we have developed procedures for preparation of an
additive-free cell extract (AFCE) and for concentrating biomacromolecules in
artificial cells. In this review, we introduce our recent progress to
reconstitute intracellular environments in vitro and in artificial cells.
PMID- 27493498
TI - Ultrasensitive enzyme-linked immunosorbent assay (ELISA) of proteins by
combination with the thio-NAD cycling method.
AB - An ultrasensitive method for the determination of proteins is described that
combines an enzyme-linked immunosorbent assay (ELISA) and a thionicotinamide
adenine dinucleotide (thio-NAD) cycling method. A sandwich method using a primary
and a secondary antibody for antigens is employed in an ELISA. An androsterone
derivative, 3alpha-hydroxysteroid, is produced by the hydrolysis of 3alpha
hydroxysteroid 3-phosphate with alkaline phosphatase linked to the secondary
antibody. This 3alpha-hydroxysteroid is oxidized to a 3-ketosteroid by 3alpha-
hydroxysteroid dehydrogenase (3alpha-HSD) with a cofactor thio-NAD. By the
opposite reaction, the 3-ketosteroid is reduced to a 3alpha-hydroxysteroid by
3alpha-HSD with a cofactor NADH. During this cycling reaction, thio-NADH
accumulates in a quadratic function-like fashion. Accumulated thio-NADH can be
measured directly at an absorbance of 400 nm without any interference from other
cofactors. These features enable us to detect a target protein with
ultrasensitivity (10(-19) mol/assay) by measuring the cumulative quantity of thio
NADH. Our ultrasensitive determination of proteins thus allows for the detection
of small amounts of proteins only by the application of thio-NAD cycling reagents
to the usual ELISA system.
PMID- 27493499
TI - Familial clustering of mice consistent to known pedigrees enabled by the genome
profiling (GP) method.
AB - Familial clustering without any prerequisite knowledge becomes often necessary in
Behavioral Science, and forensic studies in case of great disasters like Tsunami
and earthquake requiring body-identification without any usable information.
However, there has been no well-established method for this purpose although
conventional ones such as short tandem repeats (STR) and single nucleotide
polymorphism (SNP), which might be applied with toil and moil to some extent. In
this situation, we could find that the universal genome distance-measuring method
genome profiling (GP), which is made up of three elemental techniques; random
PCR, micro-temperature gradient gel electrophoresis (MUTGGE), and computer
processing for normalization, can do this purpose with ease when applied to mouse
families. We also confirmed that the sequencing approach based on the ccgf
(commonly conserved genetic fragment appearing in the genome profile) was not
completely discriminative in this case. This is the first demonstration that the
familial clustering can be attained without a priori sequence information to the
level of discriminating strains and sibling relationships. This method can
complement the conventional approaches in preliminary familial clustering.
PMID- 27493500
TI - Structural and mutation studies of two DNA demethylation related glycosylases:
MBD4 and TDG.
AB - Two mammalian DNA glycosylases, methyl-CpG binding domain protein 4 (MBD4) and
thymine DNA glycosylase (TDG), are involved in active DNA demethylation via the
base excision repair pathway. Both MBD4 and TDG excise the mismatch base from
G:X, where X is uracil, thymine, and 5-hydroxymethyluracil (5hmU). In addition,
TDG excises 5mC oxidized bases i.e. when X is 5-formylcytosine (5fC), and 5
carboxylcytosine (5caC) not 5-hydroxymethylcytosine (5hmC). A MBD4 inactive
mutant and substrate crystal structure clearly explains how MBD4 glycosylase
discriminates substrates: 5mC are not able to be directly excised, but a
deamination process from 5mC to thymine is required. On the other hand, TDG is
much more complicated; in this instance, crystal structures show that TDG
recognizes G:X mismatch DNA containing DNA and G:5caC containing DNA from the
minor groove of DNA, which suggested that TDG might recognize 5mC oxidized
product 5caC like mismatch DNA. In mutation studies, a N157D mutation results in
a more 5caC specific glycosylase, and a N191A mutation inhibits 5caC activity
while that when X=5fC or T remains. Here I revisit the recent MBD4 glycos ylase
domain co-crystal structures with DNA, as well as TDG glycosylase domain co
crystal structures with DNA in conjunction with its mutation studies.
PMID- 27493501
TI - Myosin V is a biological Brownian machine.
AB - Myosin V is a vesicle transporter that unidirectionally walks along cytoskeletal
actin filaments by converting the chemical energy of ATP into mechanical work.
Recently, it was found that myosin V force generation is a composition of two
processes: a lever-arm swing, which involves a conformational change in the
myosin molecule, and a Brownian search-and-catch, which involves a diffusive
"search" by the motor domain that is followed by an asymmetric "catch" in the
forward actin target such that Brownian motion is rectified. Here we developed a
system that combines optical tweezers with DNA nano-material to show that the
Brownian search-and-catch mechanism is the energetically dominant process at near
stall force, providing 13 kBT of work compared to just 3 kBT by the lever-arm
swing. Our result significantly reconsiders the lever-arm swinging model, which
assumes the swing dominantly produces work (>10 kBT), and sheds light on the
Brownian search-and-catch as a driving process.
PMID- 27493502
TI - Morphological and physiological characteristics of dermal photoreceptors in
Lymnaea stagnalis.
AB - Dermal photoreceptors located in the mantle of Lymnaea stagnalis were
histologically and physiologically characterized. Our previous study demonstrated
that the shadow response from dermal photoreceptors induces the whole-body
withdrawal response. Through the interneuron, RPeD11, we detected that the light
off response indirectly originated from a dermal photoreceptor. Previous
observations, based on behavioral pharmacology, revealed that cyclic guanosine
monophosphate acts as a second messenger in the dermal photoreceptor.
Furthermore, gastropods possess dermal photoreceptors containing rhodopsin, as a
photopigment, and another photo-sensitive protein, arrestin, responsible for
terminating the light response. Thus, we chose three antibodies, anti-cGMP, anti
rhodopsin, and anti-beta-arrestin, to identify the dermal photoreceptor molecules
in Lymnaea mantle. Extracellular recording, using a suction electrode on the
mantle, revealed a light off-response from the right parietal nerve. Overlapping
structures, positive against each of the antibodies, were also observed. Numerous
round, granular particles of 3-47 MUm in diameter with one nucleus were
distributed around pneumostome and/or inside the mantle. The cells surrounding
the pneumostome area, located 10 MUm beneath the surface, tended to have smaller
cell soma ranging from 3 to 25 MUm in diameter, while cells located in other
areas were distributed uniformly inside the mantle, with a larger diameter
ranging from 12 to 47 MUm. The histological examination using back-filing Lucifer
Yellow staining of the right parietal nerve with the three dermal photoreceptor
antibodies confirmed that these overlapping-stained structures were dermal
photoreceptors in Lymnaea.
PMID- 27493503
TI - 3-D structural analysis of the crucial intermediate of skeletal muscle myosin and
its role in revised actomyosin cross-bridge cycle.
AB - Skeletal myosin S1 consists of two functional segments, a catalytic-domain and a
lever-arm. Since the crystal structure of ADP/Vi-bound S1 exhibits a strong
intramolecular flexure between two segments, inter-conversion between bent and
extended forms; i.e. "tilting of the lever-arm" has been accepted as the
established molecular mechanism of skeletal muscle contraction. We utilized quick
freeze deep-etch replica electron microscopy to directly visualize the structure
of in vitro actin-sliding myosin, and found the existence of a novel oppositely
bent configuration, instead of the expected ADP/Vi-bound form. We also noticed
that SH1-SH2 cross-linked myosin gives an aberrant appearance similar to the
above structure. Since SH1-SH2-cross-linked myosin is a well-studied analogue of
the transient intermediate of the actomyosin cross-bridge cycle, we devised a new
image-processing procedure to define the relative view-angles between the
catalytic-domain and the lever-arm from those averaged images, and built a 3-D
model of the new conformer. The lever-arm in that model was bent oppositely to
the ADP/Vi-bound form, in accordance with observed actin-sliding cross-bridge
structure. Introducing this conformer as the crucial intermediate that
transiently appears during sliding, we propose a revised scheme of the cross
bridge cycle. In the scenario, the novel conformer keeps actin-binding in two
different modes until it forms a primed configuration. The final extension of the
lever-arm back to the original rigor-state constitutes the "power-stroke".
Various images observed during sliding could be easily interpreted by the new
conformer. Even the enigmatic behavior of the cross-bridges reported as "loose
chemo-mechanical coupling" might be adequately explained under some assumptions.
PMID- 27493504
TI - Cooperation between phenotypic plasticity and genetic mutations can account for
the cumulative selection in evolution.
AB - We propose the cooperative model of phenotype-driven evolution, in which natural
selection operates on a phenotype caused by both genetic and epigenetic factors.
The conventional theory of evolutionary synthesis assumes that a phenotypic value
(P) is the sum of genotypic value (G) and environmental deviation (E), P=G+E,
where E is the fluctuations of the phenotype among individuals in the absence of
environmental changes. In contrast, the cooperative model assumes that an
evolution is triggered by an environmental change and individuals respond to the
change by phenotypic plasticity (epigenetic changes). The phenotypic plasticity,
while essentially qualitative, is denoted by a quantitative value F which is
modeled as a normal random variable like E, but with a much larger variance.
Thus, the fundamental equation of the cooperative model is given as P=G+F where F
includes the effect of E. Computer simulations using a genetic algorithm
demonstrated that the cooperative model realized much faster evolution than the
evolutionary synthesis. This accelerated evolution was found to be due to the
cumulative evolution made possible by a ratchet mechanism due to the epigenetic
contribution to the phenotypic value. The cooperative model can well account for
the phenomenon of genetic assimilation, which, in turn, suggests the mechanism of
cumulative selection. The cooperative model may also serve as a theoretical basis
to understand various ideas and phenomena of the phenotype-driven evolution such
as genetic assimilation, the theory of facilitated phenotypic variation, and
epigenetic inheritance over generations.
PMID- 27493505
TI - Microscopic heat pulse-induced calcium dynamics in single WI-38 fibroblasts.
AB - Temperature-sensitive Ca(2+) dynamics occur primarily through transient receptor
potential channels, but also by means of Ca(2+) channels and pumps on the
endoplasmic reticulum membrane. As such, cytoplasmic Ca(2+) concentration
([Ca(2+)]cyt) is re-equilibrated by changes in ambient temperature. The present
study investigated the effects of heat pulses (heating duration: 2 s or 150 s) on
[Ca(2+)]cyt in single WI-38 fibroblasts, which are considered as normal cells. We
found that Ca(2+) burst occurred immediately after short (2 s) heat pulse, which
is similar to our previous report on HeLa cells, but with less thermosensitivity.
The heat pulses originated from a focused 1455-nm infrared laser light were
applied in the vicinity of cells under the optical microscope. Ca(2+) bursts
induced by the heat pulse were suppressed by treating cells with inhibitors for
sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA) or inositol trisphosphate
receptor (IP3R). Long (150 s) heat pulses also induced Ca(2+) bursts after the
onset of heating and immediately after re-cooling. Cells were more
thermosensitive at physiological (37 degrees C) than at room (25 degrees C)
temperature; however, at 37 degrees C, cells were responsive at a higher
temperature (ambient temperature+heat pulse). These results strongly suggest that
the heat pulse-induced Ca(2+) burst is caused by a transient imbalance in Ca(2+)
flow between SERCA and IP3R, and offer a potential new method for thermally
controlling Ca(2+)-regulated cellular functions.
PMID- 27493506
TI - Electrophysiological characteristics of feeding-related neurons after taste
avoidance Pavlovian conditioning in Lymnaea stagnalis.
AB - Taste avoidance conditioning (TAC) was carried out on the pond snail, Lymnaea
stagnalis. The conditional stimulus (CS) was sucrose which elicits feeding
behavior; while the unconditional stimulus (US) was a tactile stimulus to the
head which causes feeding to be suppressed. The neuronal circuit that drives
feeding behavior in Lymnaea is well worked out. We therefore compared the
physiological characteristics on 3 classes of neurons involved with feeding
behavior especially in response to the CS in conditioned vs. control snails. The
cerebral giant cell (CGC) modulates feeding behavior, N1 medial neuron (N1M) is
one of the central pattern generator neurons that organizes feeding behavior,
while B3 is a motor neuron active during the rasp phase of feeding. We found the
resting membrane potential in CGC was hyperpolarized significantly in conditioned
snails but impulse activity remained the same between conditioned vs. control
snails. There was, however, a significant increase in spontaneous activity and a
significant depolarization of N1M's resting membrane potential in conditioned
snails. These changes in N1M activity as a result of training are thought to be
due to withdrawal interneuron RPeD11 altering the activity of the CGCs. Finally,
in B3 there was: 1) a significant decrease in the amplitude and the frequency of
the post-synaptic potentials; 2) a significant hyperpolarization of resting
membrane potential in conditioned snails; and 3) a disappearance of bursting
activity typically initiated by the CS. These neuronal modifications are
consistent with the behavioral phenotype elicited by the CS following
conditioning.
PMID- 27493507
TI - Effects of serotonin on the heartbeat of pond snails in a hunger state.
AB - Serotonin (5-hydroxytryptamine: 5-HT) is a multimodal transmitter that controls
both feeding response and heartbeat in snails. However, the effects of 5-HT on
the hunger state are still unknown. We therefore examined the relation among the
hunger state, the heartbeat rate and the 5-HT action in food-starved snails. We
found that the hunger state was significantly distinguished by the heartbeat rate
in snails. The heartbeat rate was high in the food-satiated snails, whereas it
was low in the food-starved snails. An increase in 5-HT concentration in the body
boosted the heartbeat rate in the food-starved snails, but did not affect the
rate in the food-satiated snails. These results suggest that 5-HT application may
mimic the change from a starvation to a satiation state normally achieved by
direct ingestion of food.
PMID- 27493508
TI - Preface of Special Issue "TRP channels: their functional roles in medical
sciences".
PMID- 27493509
TI - Electrophysiological characteristics of IB4-negative TRPV1-expressing muscle
afferent DRG neurons.
AB - Muscle afferent neurons that express transient receptor potential vanilloid type
I (TRPV1) are responsible for muscle pain associated with tissue acidosis. We
have previously found that TRPV1 of isolectin B4 (IB4)-negative muscle
nociceptors plays an important role in the acid-induced hyperalgesic priming and
the development of chronic hyperalgesia in a mouse model of fibromyalgia. To
understand the electrophysiological properties of the TRPV1-expressing muscle
afferent neurons, we used whole-cell patch clamp recording to study the acid
responsiveness and action potential (AP) configuration of capsaicin-sensitive
neurons innervating to gastrocnemius muscle. Here we showed that IB4-negative
TRPV1-expressing muscle afferent neurons are heterogeneous in terms of cell size,
resting membrane potential, AP configuration, tetrodotoxin (TTX)-resistance, and
acid-induced current (I acid), as well as capsaicin-induced current (I cap).
TRPV1-expressing neurons were all acid-sensitive and could be divided into two
acid-sensitive groups depending on an acid-induced sustained current (type I) or
an acid-induced biphasic ASIC3-like current (type II). Type I TRPV1-expressing
neurons were distinguishable from type II TRPV1-expressing neurons in AP
overshoot, after-hyperpolarization duration, and all I acid parameters, but not
in AP threshold, TTX-resistance, resting membrane potential, and I cap
parameters. These differential biophysical properties of TRPV1-expressing neurons
might partially annotate their different roles involved in the development and
maintenance of chronic muscle pain.
PMID- 27493510
TI - TRP channels in skin: from physiological implications to clinical significances.
AB - TRP channels are expressed in various cells in skin. As an organ system to border
the host and environment, many nonneuronal cells, including epidermal
keratinocytes and melanocytes, express several TRP channels functionally distinct
from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and
hair apparatus inhibit proliferation, induce terminal differentiation, induce
apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes
regeneration of the severed skin barriers. TRPA1 also enhances responses in
contact hypersensitivity. TRPCs in keratinocytes regulate epidermal
differentiation. In human diseases with pertubered epidermal differentiation, the
expression of TRPCs are altered. TRPMs, which contribute to melanin production in
melanocytes, serve as significant prognosis markers in patients with metastatic
melanoma. In summary, not only act in sensory processing, TRP channels also
contribute to epidermal differentiation, proliferation, barrier integration, skin
regeneration, and immune responses. In diseases with aberrant TRP channels, TRP
channels might be good therapeutic targets.
PMID- 27493511
TI - Role of TRP channels in the induction of heat shock proteins (Hsps) by heating
skin.
AB - Transient receptor potential (TRP) channels in skin are crucial for achieving
temperature sensitivity to maintain internal temperature balance and thermal
homeostasis, as well as to protect skin cells from environmental stresses such as
infrared (IR) or near-infrared (NIR) radiation via heat shock protein (Hsp)
production. However, the mechanisms by which IR and NIR activate TRP channels and
produce Hsps intracellularly have been independently reported. In this review, we
discuss the relationship between TRP channel activation and Hsp production, and
introduce the roles of several skin TRP channels in the regulation of HSP
production by IR and NIR exposure.
PMID- 27493512
TI - Thermodynamic implications of high Q 10 of thermo-TRP channels in living cells.
AB - The activity of thermo-transient receptor potential (TRP) channels is highly
dependent on temperature, and thus thermo-TRP reactions have a high temperature
coefficient Q 10. In thermodynamics, a high value of Q 10 indicates the existence
of a large activation energy (i.e., a large enthalpy) over a short period during
the transition process between the closed and open states of the channels. The
Gibbs free energy equation shows that a large entropy is required to compensate
for this large enthalpy and permit activation of the channels, suggesting a large
conformational change of the channels. These large values of enthalpy and entropy
seem to be a match for the values of the unfolding process of globular proteins.
We outline these thermodynamic issues in thermo-TRPs.
PMID- 27493513
TI - FTIR study of CPD photolyase with substrate in single strand DNA.
AB - Photolyases (PHRs) utilize near UV/blue light to specifically repair the major
photoproducts (PPs) of UV-induced damaged DNA. The cyclobutane pyrimidine dimer
(CPD)-PHR binds flavin adenine dinucleotide (FAD) as a cofactor and repairs CPD
lesions in double-stranded DNA. To understand the activation and repair mechanism
of CPD-PHR, we applied light-induced difference Fourier transform infrared (FTIR)
spectroscopy to CPD-PHR, whose signals were identified by use of isotope
labeling. To further investigate the enzymatic function, here we study the
activation and repair mechanism of CPD-PHR with the substrate in single strand
DNA, and the obtained FTIR spectra are compared with those in double-stranded
DNA, the natural substrate. The difference spectra of photoactivation, the fully
reduced (FADH(-)) minus semiquinone (FADH(*)) spectra, are almost identical in
the presence of single strand and double-stranded DNA, except for slight spectral
modification in the amide-I region. On the other hand, the difference spectra of
photorepair were highly substrate dependent. Strong bands of the C=O stretch
(1,720-1,690 cm(-1)) and phosphate vibrations (1,090-1,060 cm(-1)) of double
stranded DNA may have disappeared in the case of single strand DNA. However, an
isotope-labeled enzyme study revealed that spectral features upon DNA repair are
similar between both substrates, and the main reason for the apparent spectral
difference originates from structural flexibility of DNA after repair.
PMID- 27493514
TI - Lever arm extension of myosin VI is unnecessary for the adjacent binding state.
AB - Myosin VI is a processive myosin that has a unique stepping motion, which
includes three kinds of steps: a large forward step, a small forward step and a
backward step. Recently, we proposed the parallel lever arms model to explain the
adjacent binding state, which is necessary for the unique motion. In this model,
both lever arms are directed the same direction. However, experimental evidence
has not refuted the possibility that the adjacent binding state emerges from
myosin VI folding its lever arm extension (LAE). To clarify this issue, we
constructed a myosin VI/V chimera that replaces the myosin VI LAE with the IQ3-6
domains of the myosin V lever arm, which cannot fold, and performed single
molecule imaging. Our chimera showed the same stepping patterns as myosin VI,
indicating the LAE is not responsible for the adjacent binding state.
PMID- 27493515
TI - The activity of isolated snail neurons controlling locomotion is affected by
glucose.
AB - The involvement of serotonin in mediating hunger-related changes in behavioral
state has been described in many invertebrates. However, the mechanisms by which
hunger signals to serotonergic cells remain unknown. We tested the hypothesis
that serotonergic neurons can directly sense the concentration of glucose, a
metabolic indicator of nutritional state. In the snail Lymnaea stagnalis, we
demonstrate that completely isolated pedal serotonergic neurons that control
locomotion changed their biophysical characteristics in response to glucose
application by lowering membrane potential and decreasing the firing rate.
Additionally, the excitatory response of the isolated serotonergic neurons to the
neuroactive microenvironment of the pedal ganglia was significantly lowered by
glucose application. Because hunger has been reported to increase the activity of
select neurons and their responses to the pedal ganglia microenvironment, these
responses to glucose are in accordance with the hypothesis that direct glucose
signaling is involved in the mediation of the hunger-related behavioral state.
PMID- 27493516
TI - FTIR study of primate color visual pigments.
AB - How do we distinguish colors? Humans possess three color pigments; red-, green-,
and blue-sensitive proteins, which have maximum absorbance (lambdamax) at 560,
530, and 420 nm, respectively, and contribute to normal human trichromatic vision
(RGB). Each color pigments consists of a different opsin protein bound to a
common chromophore molecule, 11-cis-retinal, whereas different chromophore
protein interactions allow preferential absorption of different colors. However,
detailed experimental structural data to explain the molecular basis of spectral
tuning of color pigments are lacking, mainly because of the difficulty in sample
preparation. We thus started structural studies of primate color visual pigments
using low-temperature Fourier-transform infrared (FTIR) spectroscopy, which needs
only 0.3 mg protein for a single measurement. Here we report the first structural
data of monkey red- (MR) and green- (MG) sensitive pigments, in which the
information about the protein, retinal chromophore, and internal water molecules
is contained. Molecular mechanism of color discrimination between red and green
pigments will be discussed based on the structural data by FTIR spectroscopy.
PMID- 27493517
TI - In vitro directed evolution of alpha-hemolysin by liposome display.
AB - We have developed a method to enable in vitro directed evolution that can be
applied to membrane proteins. This method, termed liposome display, uses
liposomes as compartments in which membrane proteins are synthesized and as
scaffolds for membrane protein integration. Thus, the synthesized membrane
proteins are displayed on the surface of the liposome and exhibit their
functions. A randomly mutated DNA library of the membrane protein was generated,
encapsulated in the liposomes at the single-molecule level, and used to generate
a liposome library. Liposomes displaying the desired membrane protein function
were selected, thus accumulating the DNA molecule encoding the desired membrane
protein. We have applied this method to alpha-hemolysin, a membrane protein
derived from Staphylococcus aureus. Alpha-hemolysin forms a nanopore in the
membrane, which allows the penetration of small molecules. We aimed to improve
this nanopore activity by using the liposome display method. Consequently, alpha
hemolysin evolved and attained a higher specific affinity for the liposome
membrane. In this review, we describe the essential characteristics of liposome
display and the properties of the evolved alpha-hemolysin obtained by this
method.
PMID- 27493518
TI - A new antigenic marker specifically labels a subpopulation of the class II Kenyon
cells in the brain of the European honeybee Apis mellifera.
AB - The mushroom bodies are the higher-order integration center in the insect brain
and are involved in higher brain functions such as learning and memory. In the
social hymenopteran insects such as honeybees, the mushroom bodies are the
prominent brain structures. The mushroom bodies are composed of lobed neuropils
formed by thousands of parallel-projecting axons of intrinsic neurons, and the
lobes are divided into parallel subdivisions. In the present paper, we report a
new antigenic marker to label a single layer in the vertical lobes of the
European honeybee Apis mellifera. In the brain of A. mellifera, a monoclonal
antibody (mAb) 15C3, which was originally developed against an insect ecdysone
receptor (EcR) protein, immunolabels a single layer of the vertical lobes that
correspond to the most dorsal layer of the gamma-lobe. The 15C3 mAb recognizes a
single ~200 kDa protein expressed in the adult honeybee brain. In addition, the
15C3 mAb immunoreactivity was also observed in the lobes of the developing pupal
mushroom bodies. Since gamma-lobe is well known to their extensive reorganization
that occurs during metamorphosis in Drosophila, the novel antigenic marker for
the honeybee gamma-lobe allows us to investigate morphological changes of the
mushroom bodies during metamorphosis.
PMID- 27493519
TI - A protocol for preparing nucleotide-free KaiC monomer.
AB - The hexameric form of the KaiC protein is a core of the cyanobacterial biological
clock, and its enzymatic activities exhibit circadian periodicity. The
instability of the monomeric form of nucleotide-free KaiC has precluded its
storage and detailed analyses of the activities of the reassembled hexamer. Here,
we provide a protocol for preparing nucleotide-free KaiC monomer that is stable
in solution and for triggering its reassembly into intact KaiC hexamer by the
addition of ATP. A phosphate buffer containing glutamic acid and arginine
enhanced the stability of KaiC monomer considerably. In addition, we found that
reassembled KaiC hexamer was functionally active as the intact hexamer. This
protocol provides a methodological basis for further analyses of first-turnover
events of the ATPase/autokinase/autophosphatase activities of the KaiC hexamer.
PMID- 27493520
TI - Experimental and theoretical bases for mechanisms of antigen discrimination by T
cells.
AB - Interaction only within specific molecules is a requisite for accurate operations
of a biochemical reaction in a cell where bulk of background molecules exist.
While structural specificity is a well-established mechanism for specific
interaction, biophysical and biochemical experiments indicate that the mechanism
is not sufficient for accounting for the antigen discrimination by T cells. In
addition, the antigen discrimination by T cells also accompanies three intriguing
properties other than the specificity: sensitivity, speed, and concentration
compensation. In this work, we review experimental and theoretical works on the
antigen discrimination by focusing on these four properties and show future
directions towards understanding of the fundamental principle for molecular
discrimination.
PMID- 27493522
TI - Revealing the peptide presenting process of human leukocyte antigen through the
analysis of fluctuation.
AB - Structural fluctuation on microsecond to millisecond time scales has been
reported to play an important role in proteins that undergo significant
structural change during their expression of function. In these proteins, the
structural change was obvious in the crystal structures. However, protein motions
in solution could contribute to the function of proteins, even if no significant
structural difference is observed in crystal structure of different states while
they function. In this review, we introduce our recent report on the
stabilization mechanism of human leukocyte antigen, and the possibility of
fluctuation contributing to several biophysical properties of proteins.
PMID- 27493521
TI - How do chaperonins fold protein?
AB - Protein folding is a biological process that is essential for the proper
functioning of proteins in all living organisms. In cells, many proteins require
the assistance of molecular chaperones for their folding. Chaperonins belong to a
class of molecular chaperones that have been extensively studied. However, the
mechanism by which a chaperonin mediates the folding of proteins is still
controversial. Denatured proteins are folded in the closed chaperonin cage,
leading to the assumption that denatured proteins are completely encapsulated
inside the chaperonin cage. In contrast to the assumption, we recently found that
denatured protein interacts with hydrophobic residues at the subunit interfaces
of the chaperonin, and partially protrude out of the cage. In this review, we
will explain our recent results and introduce our model for the mechanism by
which chaperonins accelerate protein folding, in view of recent findings.
PMID- 27493523
TI - Chemomechanical coupling of F1-ATPase under hydrolysis conditions.
AB - F1-ATPase (F1) is the smallest rotary motor protein that couples ATP
hydrolysis/synthesis to rotary motion in a highly reversible manner. F1 is unique
compared with other motor proteins because of its high efficiency and
reversibility in converting chemical energy into mechanical work. To determine
the energy conversion mechanism of F1-ATPase, we developed a novel single
molecule manipulation technique with magnetic tweezers and determined the timing
of Pi release, which was the last unknown piece of the chemomechanical coupling
scheme of F1. The established fundamental chemomechanical coupling scheme
provides evidence to explain the high reversibility between catalysis and
mechanical work.
PMID- 27493524
TI - GIRAF: a method for fast search and flexible alignment of ligand binding
interfaces in proteins at atomic resolution.
AB - Comparison and classification of protein structures are fundamental means to
understand protein functions. Due to the computational difficulty and the ever
increasing amount of structural data, however, it is in general not feasible to
perform exhaustive all-against-all structure comparisons necessary for
comprehensive classifications. To efficiently handle such situations, we have
previously proposed a method, now called GIRAF. We herein describe further
improvements in the GIRAF protein structure search and alignment method. The
GIRAF method achieves extremely efficient search of similar structures of ligand
binding sites of proteins by exploiting database indexing of structural features
of local coordinate frames. In addition, it produces refined atom-wise alignments
by iterative applications of the Hungarian method to the bipartite graph defined
for a pair of superimposed structures. By combining the refined alignments based
on different local coordinate frames, it is made possible to align structures
involving domain movements. We provide detailed accounts for the database design,
the search and alignment algorithms as well as some benchmark results.
PMID- 27493526
TI - Comparative study of the different mechanisms for zinc ion stress sensing in two
cyanobacterial strains, Synechococcus sp. PCC 7942 and Synechocystis sp. PCC
6803.
AB - In response to an increased level of Zn(2+), Synechococcus sp. PCC 7942 expresses
SmtA, a metallothionein-like metal-chelating protein, while Synechocystis sp. PCC
6803 expresses ZiaA, a transporter of Zn(2+). The gene expression of these
proteins is regulated by repressor protein, SmtB and ZiaR, respectively. In spite
of contributing to different response systems, both repressor proteins belong to
the ArsR family and are highly homologous to each other. To understand the
different systems responsible for dealing with excess Zn(2+), we examined the cis
elements in the promoter regions of smtA and ziaA, as well as the binding
affinities of recombinant SmtB and ZiaR proteins. The operator/promoter region of
smtA included two palindromic sequences and that of ziaA included one.
Electrophoretic mobility shift assay revealed that SmtB formed four different
complexes with the operator/promoter region of smtA, whereas it formed only two
different complexes with the corresponding region of ziaA. For ZiaR, the
corresponding results were quite the same as those for SmtB. Furthermore, the
complex formation between SmtB and operator/promoter regions is inhibited in the
presence of Zn(2+) at higher concentrations than 16 MUM. On the other hand, the
corresponding Zn(2+) concentration is 128 MUM. These results demonstrate that the
degrees of protein-DNA complex formation between repressor proteins and the
operator/promoter regions of regulated genes depend on the structures of the
operator/promoter regions, and the effects of Zn(2+) on the dissociation of these
complexes are mainly associated with the structures of the repressors.
PMID- 27493525
TI - mDia1 and formins: screw cap of the actin filament.
AB - Formin homology proteins (formins) are actin nucleation factors which remain
bound to the growing barbed end and processively elongate actin filament (F
actin). Recently, we have demonstrated that a mammalian formin mDia1 rotates
along the long-pitch helix of F-actin during processive elongation (helical
rotation) by single-molecule fluorescence polarization. We have also shown
processive depolymerization of mDia1-bound F-actin during which helical rotation
was visualized. In the cell where F-actins are highly cross-linked, formins
should rotate during filament elongation. Therefore, when formins are tightly
anchored to cellular structures, formins may not elongate F-actin. Adversely,
helical rotation of formins might affect the twist of F-actin. Formins could thus
control actin elongation and regulate stability of cellular actin filaments
through helical rotation. On the other hand, ADP-actin elongation at the mDia1
bound barbed end turned out to become decelerated by profilin, in marked contrast
to its remarkably positive effect on mDia1-mediated ATP-actin elongation. This
deceleration is caused by enhancement of the off-rate of ADP-actin. While mDia1
and profilin enhance the ADP-actin off-rate, they do not apparently increase the
ADP-actin on-rate at the barbed end. These results imply that G-actin-bound ATP
and its hydrolysis may be part of the acceleration mechanism of formin-mediated
actin elongation.
PMID- 27493527
TI - Extraction and purification of a luminiferous substance from the luminous
mushroom Mycena chlorophos.
AB - Bioluminescence has attracted considerable attention in the area of biophysics,
primarily because the phenomenon can fundamentally be interpreted as the
conversion of chemical to light energy. Although the molecular mechanisms
underlying luminescence have been studied extensively in fireflies and bacteria,
few studies have been undertaken in luminous fungi. This relative lack of
information is likely due to the absence of a common and species-specific
reaction-type in the luminous fungi examined to date. We recently succeeded in
extracting, for the first time, a luminiferous substance from the fungus Mycena
chlorophos. The substance was purified and characterized according to its
chemical and optical properties. It is hoped that this information will
facilitate the clarification of a novel molecular mechanism in fungal
bioluminescence systems.
PMID- 27493528
TI - Full-Quantum chemical calculation of the absorption maximum of bacteriorhodopsin:
a comprehensive analysis of the amino acid residues contributing to the opsin
shift.
AB - Herein, the absorption maximum of bacteriorhodopsin (bR) is calculated using our
recently developed method in which the whole protein can be treated quantum
mechanically at the level of INDO/S-CIS//ONIOM (B3LYP/6-31G(d,p): AMBER). The
full quantum mechanical calculation is shown to reproduce the so-called opsin
shift of bR with an error of less than 0.04 eV. We also apply the same
calculation for 226 different bR mutants, each of which was constructed by
replacing any one of the amino acid residues of the wild-type bR with Gly. This
substitution makes it possible to elucidate the extent to which each amino acid
contributes to the opsin shift and to estimate the inter-residue synergistic
effect. It was found that one of the most important contributions to the opsin
shift is the electron transfer from Tyr185 to the chromophore upon excitation. We
also indicate that some aromatic (Trp86, Trp182) and polar (Ser141, Thr142)
residues, located in the vicinity of the retinal polyene chain and the beta
ionone ring, respectively, play an important role in compensating for the large
blue-shift induced by both the counterion residues (Asp85, Asp212) and an
internal water molecule (W402) located near the Schiff base linkage. In
particular, the effect of Trp86 is comparable to that of Tyr185. In addition,
Ser141 and Thr142 were found to contribute to an increase in the dipole moment of
bR in the excited state. Finally, we provide a complete energy diagram for the
opsin shift together with the contribution of the chromophore-protein steric
interaction.
PMID- 27493529
TI - A scoring function based on solvation thermodynamics for protein structure
prediction.
AB - We predict protein structure using our recently developed free energy function
for describing protein stability, which is focused on solvation thermodynamics.
The function is combined with the current most reliable sampling methods, i.e.,
fragment assembly (FA) and comparative modeling (CM). The prediction is tested
using 11 small proteins for which high-resolution crystal structures are
available. For 8 of these proteins, sequence similarities are found in the
database, and the prediction is performed with CM. Fairly accurate models with
average Calpha root mean square deviation (RMSD) ~ 2.0 A are successfully
obtained for all cases. For the rest of the target proteins, we perform the
prediction following FA protocols. For 2 cases, we obtain predicted models with
an RMSD ~ 3.0 A as the best-scored structures. For the other case, the RMSD
remains larger than 7 A. For all the 11 target proteins, our scoring function
identifies the experimentally determined native structure as the best structure.
Starting from the predicted structure, replica exchange molecular dynamics is
performed to further refine the structures. However, we are unable to improve its
RMSD toward the experimental structure. The exhaustive sampling by coarse-grained
normal mode analysis around the native structures reveals that our function has a
linear correlation with RMSDs < 3.0 A. These results suggest that the function is
quite reliable for the protein structure prediction while the sampling method
remains one of the major limiting factors in it. The aspects through which the
methodology could further be improved are discussed.
PMID- 27493530
TI - Virtual states introduced for overcoming entropic barriers in conformational
space.
AB - Free-energy landscape is an important quantity to study large-scale motions of a
biomolecular system because it maps possible pathways for the motions. When the
landscape consists of thermodynamically stable states (low-energy basins), which
are connected by narrow conformational pathways (i.e., bottlenecks), the
narrowness slows the inter-basin round trips in conformational sampling. This
results in inaccuracy of free energies for the basins. This difficulty is not
cleared out even when an enhanced conformational sampling is fairly performed
along a reaction coordinate. In this study, to enhance the inter-basin round
trips we introduced a virtual state that covers the narrow pathways. The
probability distribution function for the virtual state was controlled based on
detailed balance condition for the inter-state transitions (transitions between
the real-state basins and the virtual state). To mimic the free-energy landscape
of a real biological system, we introduced a simple model where a wall separates
two basins and a narrow hole is pierced in the wall to connect the basins. The
sampling was done based on Monte Carlo (MC). We examined several hole-sizes and
inter-state transition probabilities. For a small hole-size, a small inter-state
transition probability produced a sampling efficiency 100 times higher than a
conventional MC does. This result goes against ones intuition, because one
considers generally that the sampling efficiency increases with increasing the
transition probability. The present method is readily applicable to enhanced
conformational sampling such as multi-canonical or adaptive umbrella sampling,
and extendable to molecular dynamics.
PMID- 27493531
TI - Mechanistic insights from the recent structures of the CRM1 nuclear export
complex and its disassembly intermediate.
AB - CRM1 (also known as exportin 1 or Xpo1) is the most versatile nuclear export
receptor (exportin) that carries a broad range of proteins and ribonucleoproteins
from the nucleus to the cytoplasm through the nuclear pore complex. The majority
of the export substrates of CRM1 contain a short peptide sequence, so-called
leucine-rich nuclear export signal (NES), which typically harbor four or five
characteristically spaced hydrophobic residues. The transport directionality is
determined by the small GTPase Ran and Ran-binding proteins that control the
binding and dissociation of cargo. Here we review recent structural studies that
advanced understanding of how NES is specifically recognized by CRM1 in the
nucleus, and how NES is rapidly dissociated from CRM1 in the cytoplasm.
PMID- 27493532
TI - Proposed model for the flagellar rotary motor with shear stress transmission.
AB - Most bacteria that swim are propelled by flagellar filaments, which are driven by
a rotary motor powered by proton flux. The motor consists of the rotor and the
stator. The stator consists of about 8 MotA-Mot B complex. There seems to be no
definite information about the structure between the rotor and the stator, and it
is examined whether the experimental data can be explained based upon the
following assumptions. (a) There is viscoelastic medium between the rotor and the
stator. (b) MotA-MotB complex has an electric dipole moment and produces shear
stress in the electric field by a proton in the channel. Calculation results
based upon these assumptions are in good agreement with the following
experimental observations. (1) One revolution of the flagellar rotation consists
of a constant number of steps. (2) The rotation velocity of the rotor is
proportional to the trans-membrane potential difference. (3) When the rotational
velocity of a flagellum is changed by adjusting the viscosity of the outer fluid,
the torque for the cell to rotate a flagellum is practically constant but sharply
decreases when the rotational velocity increases over a critical value. (4) The
rotation direction remains the same when the sign of the electrochemical
potential gradient is reversed. (5) The cell produces constant torque to rotate
the flagellum even when the cell is rotated by externally applied torque. (6) A
simple switch mechanism is proposed for chemotaxis.
PMID- 27493533
TI - Self-oscillating gels beating like a heart muscle.
AB - So far stimuli-responsive polymer gels and their application to smart materials
have been widely studied. On the other hand, as a novel biomimetic gel, we
developed gels with an autonomous self-oscillating function like a heart muscle,
which was firstly reported in 1996. We designed the self-oscillating polymers and
gels by utilizing the oscillating reaction, called the Belousov-Zhabotinsky (BZ)
reaction. The self-oscillating polymer is composed of a poly(N
isopropylacrylamide) network in which the catalyst for the BZ reaction is
covalently immobilized. In the presence of the reactants, the polymer gel
undergoes spontaneous cyclic swelling-deswelling changes without any on-off
switching of external stimuli. Potential applications of the self-oscillating
polymers and gels include several kinds of functional material systems, such as
bio-mimetic actuators and mass transport surface. In this review, recent progress
on the polymer gels is introduced.
PMID- 27493534
TI - Phase dependency of long-term potentiation induction during the intermittent
bursts of carbachol-induced beta oscillation in rat hippocampal slices.
AB - The rodent hippocampus possesses theta (theta) and beta (beta) rhythms, which
occur intermittently as bursts. Both rhythms are related to spatial memory
processing in a novel environment. theta rhythm is related to spatial memory
encoding process. beta rhythm is related to the match/mismatch process. In the
match/mismatch process, rodent hippocampus detects a representation matching
sensory inputs of the current place among the retrieved internal representations
of places. Long-term synaptic potentiation (LTP) is induced in both processes.
The cholinergic agent carbachol induces intermittent theta and beta oscillations
in in vitro slices similar to in vivo bursts. LTP is facilitated during the
generation of theta oscillation, suggesting that the facilitation of LTP is
dependent upon the phases of intermittent burst (burst phases) of the
oscillation. However, whether this is the case for beta oscillation has not yet
been studied. In the present study, LTP-inducing theta-burst stimulation was
administered at the different burst phases of carbachol-induced beta oscillations
(CIBO), and the synaptic changes were measured at CA3-CA3 pyramidal cell synapses
(CA3 synapse) and at CA3-CA1 pyramidal cell synapses (CA1 synapse). At the CA3
synapse, the largest magnitude of LTP was induced at the late burst phases of
CIBO. At the CA1 synapse, LTP was induced only at the late burst phases.
Modulation of LTP was suppressed when CIBO was blocked by the application of
atropine at both synapses. The results suggest that the bursts of hippocampal
beta rhythm can determine the optimal temporal period for completing with the
match/mismatch process.
PMID- 27493535
TI - Distinct Conformation of ATP Molecule in Solution and on Protein.
AB - Adenosine triphosphate (ATP) is a versatile molecule used mainly for energy and a
phosphate source. The hydrolysis of gamma phosphate initiates the reactions and
these reactions almost always start when ATP binds to protein. Therefore, there
should be a mechanism to prevent spontaneous hydrolysis reaction and a mechanism
to lead ATP to a pure energy source or to a phosphate source. To address these
questions, we extensively analyzed the effect of protein to ATP conformation
based on the sampling of the ATP solution conformations obtained from molecular
dynamics simulation and the sampling of ATP structures bound to protein found in
a protein structure database. The comparison revealed mainly the following three
points; 1) The ribose ring in ATP molecule, which puckers in many ways in
solution, tends to assume either C2' exo or C2' endo when it binds to protein. 2)
The adenine ring in ATP molecule, which takes open-book motion with the two ring
structures, has two distinct structures when ATP binds to protein. 3) The
glycosyl-bond and the bond between phosphate and the ribose have unique torsion
angles, when ATP binds to protein. The combination of torsion angles found in
protein-bound forms is under-represented in ATP molecule in water. These findings
suggest that ATP-binding protein exerts forces on ATP molecule to assume a
conformation that is rarely found in solution, and that this conformation change
should be a trigger for the reactions on ATP molecule.
PMID- 27493536
TI - Single turnovers of fluorescent ATP bound to bipolar myosin filament during actin
filaments sliding.
AB - The nucleotide turnover rates of bipolar myosin thick filament along which actin
filament slides were measured by the displacement of prebound fluorescent ATP
analog 2'(3')-O-[N-[2-[(Cy3)]amindo]ethyl] carbamoyl]-adenosine 5' triphosphate
(Cy3-EDA-ATP) upon flash photolysis of caged ATP. The fluorescence of the thick
filament where actin filament slides decayed with two exponential processes. The
slower rate constant was the same as that without actin filament. Along bipolar
myosin thick filament, actin filaments slide at a fast speed towards the central
bare zone (forward), but more slowly away from the bare zone (backward). The
displacement rate constant of fluorescent ATP from the myosin filament where
actin filament moved forward was 5.0 s(-1), whereas the rate constant where the
actin filament slid backward was 1.7 s(-1). These findings suggest that the slow
ADP release rate is responsible for the slow backward sliding movement.
PMID- 27493537
TI - Expression, purification and biochemical characterization of the cytoplasmic loop
of PomA, a stator component of the Na(+) driven flagellar motor.
AB - Flagellar motors embedded in bacterial membranes are molecular machines powered
by specific ion flows. Each motor is composed of a stator and a rotor and the
interactions of those components are believed to generate the torque. Na(+)
influx through the PomA/PomB stator complex of Vibrio alginolyticus is coupled to
torque generation and is speculated to trigger structural changes in the
cytoplasmic domain of PomA that interacts with a rotor protein in the C-ring,
FliG, to drive the rotation. In this study, we tried to overproduce the
cytoplasmic loop of PomA (PomA-Loop), but it was insoluble. Thus, we made a
fusion protein with a small soluble tag (GB1) which allowed us to express and
characterize the recombinant protein. The structure of the PomA-Loop seems to be
very elongated or has a loose tertiary structure. When the PomA-Loop protein was
produced in E. coli, a slight dominant effect was observed on motility. We
conclude that the cytoplasmic loop alone retains a certain function.
PMID- 27493538
TI - Mechanism of the nucleotidyl-transfer reaction in DNA polymerase revealed by time
resolved protein crystallography.
AB - Nucleotidyl-transfer reaction catalyzed by DNA polymerase is a fundamental
enzymatic reaction for DNA synthesis. Until now, a number of structural and
kinetic studies on DNA polymerases have proposed a two-metalion mechanism of the
nucleotidyl-transfer reaction. However, the actual reaction process has never
been visualized. Recently, we have followed the nucleotidyl-transfer reaction
process by human DNA polymerase eta using time-resolved protein crystallography.
In sequence, two Mg(2+) ions bind to the active site, the nucleophile 3'-OH is
deprotonated, the deoxyribose at the primer end converts from C2'-endo to C3'
endo, and the nucleophile and the alpha-phosphate of the substrate dATP approach
each other to form the new bond. In this process, we observed transient elements,
which are a water molecule to deprotonate the 3'-OH and an additional Mg(2+) ion
to stabilize the intermediate state. Particularly, the third Mg(2+) ion observed
in this study may be a general feature of the two-metalion mechanism.
PMID- 27493539
TI - Characterization of the ordered phase formed by sphingomyelin analogues and
cholesterol binary mixtures.
AB - The influences of structural alterations of sphingomyelin (SM) on its
interactions with cholesterol (chol) and on ordered phase formation were examined
by density measurements and surface pressure vs. molecular area isotherm
measurements. In addition, we quantitatively characterized the ordered phase
formed in each SM and chol binary mixture on the basis of the molecular
compressional modulus of SM ( [Formula: see text]). Density measurements
demonstrated that the ordered phase formation in threo-SM (tSM)/chol and
dihydrosphingomyelin (DHSM)/chol binary bilayers shows similar chol concentration
dependency to that of natural erythro-SM (eSM)/chol bilayers; the ordered phase
formation was completed in the presence of 25 mol% chol. In contrast, SM bearing
a triple bond in the place of a double bond (tripleSM) required a greater
concentration of chol to completely transform the bilayer into the ordered phase
(at 40 mol% chol). Surface pressure vs. molecular area isotherms showed that the
DHSM molecule ( [Formula: see text] = 290 mN/m) is more rigid than eSM (
[Formula: see text] = 240 mN/m) above 30 mol% chol (in the ordered phase),
although these values are similar (140-150 mN/m) in the absence of chol (liquid
condensed phase). Most likely, the DHSM/chol mixture forms a more ordered
membrane than the eSM/chol mixture does. Moreover, in the absence of chol, the
rigidity of the tripleSM molecule ( [Formula: see text] = 250 mN/m) is
significantly higher as compared with that of the eSM molecule ( [Formula: see
text] = 150 mN/m), which is probably due to the presence of a triple bond.
PMID- 27493540
TI - Rotary catalysis of FoF1-ATP synthase.
AB - The synthesis of ATP, the key reaction of biological energy metabolism, is
accomplished by the rotary motor protein; FoF1-ATP synthase (FoF1). In vivo,
FoF1, located on the cell membrane, carries out ATP synthesis by using the proton
motive force. This heterologous energy conversion is supposed to be mediated by
the mechanical rotation of FoF1; however, it still remained unclear. Recently, we
developed the novel experimental setup to reproduce the proton motive force in
vitro and succeeded in directly observing the proton-driven rotation of FoF1. In
this review, we describe the interesting working principles determined so far for
FoF1 and then introduce results from our recent study.
PMID- 27493541
TI - Crystal structure of channelrhodopsin, a light-gated cation channel - all cations
lead through the monomer.
AB - Channelrhodopsin (ChR) is a light-gated cation channel derived from green algae.
Since the inward flow of cations triggers the neuron firing, neurons expressing
ChRs can be optically controlled even within freely moving mammals. Although ChR
has been broadly applied to neuro-science research, little is known about its
molecular mechanisms. We determined the crystal structure of chimeric ChR at 2.3
A resolution and revealed its molecular architecture. The integration of
structural, electrophysio-logical, and computational analyses provided insight
into the molecular basis for the channel function of ChR, and paved the way for
the principled design of ChR variants with novel properties.
PMID- 27493542
TI - Role of the Dc domain of the bacterial hook protein FlgE in hook assembly and
function.
AB - The bacterial flagellar hook acts as a universal joint to smoothly transmit
torque produced by the motor to the filament. The hook protein FlgE assembles
into a 55 nm tubular structure with the help of the hook cap (FlgD). FlgE
consists of four domains, D0, Dc, D1 and D2, arranged from the inner to the outer
part of the tubular structure of the hook. The Dc domain contributes to the
structural stability of the hook, but it is unclear how this Dc domain is
responsible for the universal joint mechanism. Here, we carried out a deletion
analysis of the FlgE Dc domain. FlgEDelta4/5 with deletion of residues 30 to 49
was not secreted into the culture media. FlgEDelta5 and FlgEDelta6 with deletions
of residues 40 to 49 and 50 to 59, respectively, still formed hooks, allowing the
export apparatus to export the hook-filament junction proteins FlgK and FlgL and
flagellin FliC. However, these deletions inhibited the replacement of the FlgD
hook cap by FlgK at the hook tip, thereby abolishing filament formation. Deletion
of residues 50 to 59 significantly affected hook morphology. These results
suggest that the Dc domain is responsible not only for hook assembly but also for
FlgE export, the interaction with FlgK, and the polymorphic supercoiling
mechanism of the hook.
PMID- 27493543
TI - Responses of chromosome segregation machinery to mechanical perturbations.
AB - For genome stability, the proper segregation of chromosomes is required. The
exquisite process of chromosome segregation has charmed a lot of cell- and
molecular biologists into watching what happens inside a mitotic cell and how
each molecule contributes to this process for the accomplishment of accurate cell
division1. The process to partition the duplicated genome to the daughter cells
in each cell division is mediated by a self-organized structure called the
mitotic spindle. It is well known that the mitotic spindle is a multi-component
macromolecular machine composed of microtubules, molecular motors (kinesins,
cytoplasmic dynein), and other regulatory molecules (microtubule-associated
proteins, kinases, etc.). In recent years, most of the protein components of the
mitotic spindle have been identified and the functions of these proteins have
been characterized using molecular perturbations2,3. Thus, the mechanisms for
spindle assembly and chromosome segregation are being revealed rapidly. However,
the chromosome segregation machinery is poorly understood from the mechanical
point of view, such as how the mitotic spindle within a cell responds to a
variety of mechanical forces, originating from cell-cell interactions or
environmental fluctuations. Recent advances in the controlled mechanical
perturbation have indicated that the mitotic spindle possesses a structural
pliability, size adaptability to the applied external forces, and a strong self
organizing ability. Mechanical perturbations revealed also the mechanochemical
regulation of chromosome segregation machinery, which responds to the applied
forces. Here, we discuss the current progress in the biophysical research on the
architectural and functional dynamics of the mitotic spindle.
PMID- 27493544
TI - A new approach to detect small peptides clearly and sensitively by Western
blotting using a vacuum-assisted detection method.
AB - Western blotting is a widely used technique for the detection and quantification
of proteins and peptides. However, it is challenging to detect small peptides
efficiently by the conventional Western blotting method with shaking, in part
because the peptides readily detach from the blotted membrane. Although some
modified Western blotting protocols have been developed to overcome this problem,
it remains difficult to prevent peptide detachment from the membrane. In this
study, we show that the previously developed vacuum-assisted detection method
greatly improves the detection of small peptides without additional protocol
modification. The vacuum-assisted method was developed to shorten the time
required for all immunodetection steps, and all the Western blotting solutions
penetrated the membrane quickly and efficiently by this method. By using this
vacuum method, we succeeded in detecting small peptides that were completely
undetectable by the conventional Western blotting method. We also confirmed that
peptide detachment was induced even by gentle shaking in the case of the
conventional method, and the detachment was accelerated when detergent was
present in the buffer. Unlike in the conventional method, there is no need to
shake the membrane in solution in the vacuum method. Therefore, it is thought
that the small peptides could be detected sensitively only by the vacuum method.
PMID- 27493545
TI - Contribution of a visual pigment absorption spectrum to a visual function: depth
perception in a jumping spider.
AB - Absorption spectra of visual pigments are adaptively tuned to optimize
informational capacity in most visual systems. Our recent investigation of the
eyes of the jumping spider reveals an apparent exception: the absorption
characteristics of a visual pigment cause defocusing of the image, reducing
visual acuity generally in a part of the retina. However, the amount of defocus
can theoretically provide a quantitative indication of the distance of an object.
Therefore, we proposed a novel mechanism for depth perception in jumping spiders
based on image defocus. Behavioral experiments revealed that the depth perception
of the spider depended on the wavelength of the ambient light, which affects the
amount of defocus because of chromatic aberration of the lens. This wavelength
effect on depth perception was in close agreement with theoretical predictions
based on our hypothesis. These data strongly support the hypothesis that the
depth perception mechanism of jumping spiders is based on image defocus.
PMID- 27493546
TI - Experimental thermodynamics of single molecular motor.
AB - Molecular motor is a nano-sized chemical engine that converts chemical free
energy to mechanical motions. Hence, the energetics is as important as kinetics
in order to understand its operation principle. We review experiments to evaluate
the thermodynamic properties of a rotational F1-ATPase motor (F1-motor) at a
single-molecule level. We show that the F1-motor achieves 100% thermo dynamic
efficiency at the stalled state. Furthermore, the motor reduces the internal
irreversible heat inside the motor to almost zero and achieves a highly-efficient
free energy transduction close to 100% during rotations far from quasistatic
process. We discuss the mechanism of how the F1-motor achieves such a high
efficiency, which highlights the remarkable property of the nano-sized engine F1
motor.
PMID- 27493547
TI - Difference in hydration structures between F-actin and myosin subfragment-1
detected by small-angle X-ray and neutron scattering.
AB - Hydration structures around F-actin and myosin subfragment-1 (S1), which play
central roles as counterparts in muscle contraction, were investigated by small
angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). The
radius of gyration of chymotryptic S1 was evaluated to be 41.3+/-1.1 A for SAXS,
40.1+/-3.0 A for SANS in H2O, and 37.8+/-0.8 A for SANS in D2O, respectively. The
values of the cross-sectional radius of gyration of F-actin were 25.4+/-0.03 A
for SAXS, 23.4+/-2.4 A for SANS in H2O, and 22.6 +/- 0.6 A for SANS in D2O,
respectively. These differences arise from different contributions of the
hydration shell to the scattering curves. Analysis by model calculations showed
that the hydration shell of S1 has the average density 10-15% higher than bulk
water, being the typical hydration shell. On the other hand, the hydration shell
of F-actin has the average density more than 19% higher than bulk water,
indicating that F-actin has a denser, unusual hydration structure. The results
indicate a difference in the hydration structures around F-actin and S1. The
unusual hydration structure around F-actin may have the structural property of so
called "hyper-mobile water" around F-actin.
PMID- 27493548
TI - Information-to-free-energy conversion: Utilizing thermal fluctuations.
AB - Maxwell's demon is a hypothetical creature that can convert information to free
energy. A debate that has lasted for more than 100 years has revealed that the
demon's operation does not contradict the laws of thermodynamics; hence, the
demon can be realized physically. We briefly review the first experimental
demonstration of Maxwell's demon of Szilard's engine type that converts
information to free energy. We pump heat from an isothermal environment by using
the information about the thermal fluctuations of a Brownian particle and
increase the particle's free energy.
PMID- 27493549
TI - LigandBox: A database for 3D structures of chemical compounds.
AB - A database for the 3D structures of available compounds is essential for the
virtual screening by molecular docking. We have developed the LigandBox database
(http://ligandbox.protein.osaka-u.ac.jp/ligandbox/) containing four million
available compounds, collected from the catalogues of 37 commercial suppliers,
and approved drugs and biochemical compounds taken from KEGG_DRUG, KEGG_COMPOUND
and PDB databases. Each chemical compound in the database has several 3D
conformers with hydrogen atoms and atomic charges, which are ready to be docked
into receptors using docking programs. The 3D conformations were generated using
our molecular simulation program package, myPresto. Various physical properties,
such as aqueous solubility (LogS) and carcinogenicity have also been calculated
to characterize the ADME-Tox properties of the compounds. The Web database
provides two services for compound searches: a property/chemical ID search and a
chemical structure search. The chemical structure search is performed by a
descriptor search and a maximum common substructure (MCS) search combination,
using our program kcombu. By specifying a query chemical structure, users can
find similar compounds among the millions of compounds in the database within a
few minutes. Our database is expected to assist a wide range of researchers, in
the fields of medical science, chemical biology, and biochemistry, who are
seeking to discover active chemical compounds by the virtual screening.
PMID- 27493550
TI - Development of a rapid Buffer-exchange system for time-resolved ATR-FTIR
spectroscopy with the step-scan mode.
AB - Attenuated total reflectance (ATR)-FTIR spectroscopy has been widely used to
probe protein structural changes under various stimuli, such as light absorption,
voltage change, and ligand binding, in aqueous conditions. Time-resolved
measurements require a trigger, which can be controlled electronically;
therefore, light and voltage changes are suitable. Here we developed a novel,
rapid buffer-exchange system for time-resolved ATR-FTIR spectroscopy to monitor
the ligand- or ion-binding re-action of a protein. By using the step-scan mode
(time resolution; 2.5 ms), we confirmed the completion of the buffer-exchange
reaction within ~25 ms; the process was monitored by the infrared absorption
change of a nitrate band at 1,350 cm(-1). We also demonstrated the anion-binding
reaction of a membrane protein, Natronomonas pharaonis halorhodopsin (pHR), which
binds a chloride ion in the initial anion-binding site near the retinal
chromophore. The formation of chloride- or nitrate-bound pHR was confirmed by an
increase of the retinal absorption band at 1,528 cm(-1). It also should be noted
that low sample consumption (~1 ug of protein) makes this new method a powerful
technique to understand ligand-protein and ion-protein interactions, particularly
for membrane proteins.
PMID- 27493551
TI - Recent structural studies on Dom34/aPelota and Hbs1/aEF1alpha: important factors
for solving general problems of ribosomal stall in translation.
AB - In the translation process, translating ribosomes usually move on an mRNA until
they reach the stop codon. However, when ribosomes translate an aberrant mRNA,
they stall. Then, ribosomes are rescued from the aberrant mRNA, and the aberrant
mRNA is subsequently degraded. In eukaryotes, Pelota (Dom34 in yeast) and Hbs1
are responsible for solving general problems of ribosomal stall in translation.
In archaea, aPelota and aEF1alpha, homologous to Pelota and Hbs1, respectively,
are considered to be involved in that process. In recent years, great progress
has been made in determining structures of Dom34/aPelota and Hbs1/aEF1alpha. In
this review, we focus on the functional roles of Dom34/aPelota and Hbs1/aEF1alpha
in ribosome rescue, based on recent structural studies of them. We will also
present questions to be answered by future work.
PMID- 27493552
TI - 3D structure of eukaryotic flagella/cilia by cryo-electron tomography.
AB - Flagella/cilia are motile organelles with more than 400 proteins. To understand
the mechanism of such complex systems, we need methods to describe molecular
arrange-ments and conformations three-dimensionally in vivo. Cryo-electron
tomography enabled us such a 3D structural analysis. Our group has been working
on 3D structure of flagella/cilia using this method and revealed highly ordered
and beautifully organized molecular arrangement. 3D structure gave us insights
into the mechanism to gener-ate bending motion with well defined waveforms. In
this review, I summarize our recent structural studies on fla-gella/cilia by cryo
electron tomography, mainly focusing on dynein microtubule-based ATPase motor
proteins and the radial spoke, a regulatory protein complex.
PMID- 27493553
TI - Single molecule FRET observation of kinesin-1's head-tail interaction on
microtubule.
AB - Kinesin-1 (conventional kinesin) is a molecular motor that transports various
cargo such as endoplasmic reticulum and mitochondria in cells. Its two head
domains walk along microtubule by hydrolyzing ATP, while the tail domains at the
end of the long stalk bind to the cargo. When a kinesin is not carrying cargo,
its motility and ATPase activity is inhibited by direct interactions between the
tail and head. However, the mechanism of this tail regulation is not well
understood. Here, we apply single molecule fluorescence resonance energy transfer
(smFRET) to observe this interaction in stalk-truncated kinesin. We found that
kinesin with two tails forms a folding conformation and dissociates from
microtubules, whereas kinesin with one tail remains bound to the micro-tubule and
is immobile even in the presence of ATP. We further investigated the head-tail
interaction as well as head-head coordination on the microtubule at various
nucleotide conditions. From these results, we propose a two-step inhibition model
for kinesin motility.
PMID- 27493554
TI - Increase in cyclic AMP concentration in a cerebral giant interneuron mimics part
of a memory trace for conditioned taste aversion of the pond snail.
AB - Conditioned taste aversion (CTA) can be classically conditioned in the pond snail
Lymnaea stagnalis and subsequently be consolidated into long-term memory (LTM).
The neural trace that subserves CTA-LTM can be summarized as follows: A
polysynaptic inhibitory postsynaptic potential recorded in the neuron 1 medial
(N1M) cell in the conditioned snails as a result of activation of the cerebral
giant cell (CGC) is larger and lasts longer than that in control snails. The N1M
cell is ultimately activated by the CGC via the neuron 3 tonic (N3t) cell. That
is, the inhibitory monosynaptic inputs from the N3t cell to the N1M cell are
facilitated. The N1M and N3t cells are the members of feeding central pattern
generator, whereas the CGC is a multimodal interneuron thought to play a key role
in feeding behavior. Here we examined the involvement of a second messenger,
cAMP, in the establishment of the memory trace. We injected cAMP into the CGC and
monitored the potentials of the B3 motor neuron activated by the CGC. B3 activity
is used as an index for the synaptic inputs from the N3t cell to the N1M cell. We
found that the B3 potentials were transiently enlarged. Thus, when the cAMP
concentration is increased in the CGC by taste aversion training, cAMP-induced
changes may play a key role in the establishment of a memory trace in the N3t
cell.
PMID- 27493555
TI - Detection of a protein-bound water vibration of halorhodopsin in aqueous
solution.
AB - Protein-bound water molecules play crucial roles in their structure and function,
but their detection is an experimental challenge, particularly in aqueous
solution at room temperature. By applying attenuated total reflection (ATR)
Fourier-transform infrared (FTIR) spectroscopy to a light-driven Cl(-) pump
pharaonis halorhodopsin (pHR), here we detected an O-H stretching vibration of
protein-bound water molecules in the active center. The pHR(Cl(-)) minus pHR(Br(
)) ATR-FTIR spectra show random fluctuation at 3600-3000 cm(-1), frequency window
of water vibration, which can be interpreted in terms of dynamical fluctuation of
aqueous water at room temperature. On the other hand, we observed a reproducible
spectral feature at 3617 (+)/3630 (-) cm(-1) in the pHR(Cl(-)) minus pHR(Br(-))
spectrum, which is absent in the pHR(Cl(-)) minus pHR(Cl(-)) and in the pHR(Br(
)) minus pHR(Br(-)) spectra. The water O-H stretching vibrations of pHR(Cl(-))
and pHR(Br(-)) at 3617 and 3630 cm(-1), respectively, are confirmed by light
induced difference FTIR spectra in isotope water (H2 (18)O) at 77 K. The observed
water molecule presumably binds to the active center of pHR, and alter its
hydrogen bond during the Cl(-) pumping photocycle.
PMID- 27493558
TI - Feedback control of combustion instabilities from within limit cycle oscillations
using [Formula: see text] loop-shaping and the nu-gap metric.
AB - Combustion instabilities arise owing to a two-way coupling between acoustic waves
and unsteady heat release. Oscillation amplitudes successively grow, until
nonlinear effects cause saturation into limit cycle oscillations. Feedback
control, in which an actuator modifies some combustor input in response to a
sensor measurement, can suppress combustion instabilities. Linear feedback
controllers are typically designed, using linear combustor models. However, when
activated from within limit cycle, the linear model is invalid, and such
controllers are not guaranteed to stabilize. This work develops a feedback
control strategy guaranteed to stabilize from within limit cycle oscillations. A
low-order model of a simple combustor, exhibiting the essential features of more
complex systems, is presented. Linear plane acoustic wave modelling is combined
with a weakly nonlinear describing function for the flame. The latter is
determined numerically using a level set approach. Its implication is that the
open-loop transfer function (OLTF) needed for controller design varies with
oscillation level. The difference between the mean and the rest of the OLTFs is
characterized using the nu-gap metric, providing the minimum required 'robustness
margin' for an [Formula: see text] loop-shaping controller. Such controllers are
designed and achieve stability both for linear fluctuations and from within limit
cycle oscillations.
PMID- 27493557
TI - Physical aspects of sensory transduction on seeing, hearing and smelling.
AB - What is the general principle of sensory transduction? Sensory transduction is
defined as energy transformation from the external world to the internal world.
The energy of the external world, such as thermal energy (heat), electro-magnetic
energy (light), mechanical energy (sound) and the energy from molecules
(chemicals), is converted into electrochemical events in the animal nervous
system. The following five classes of special sense receptors are utilized for
energy conversion: vision (photo); audition (sound); taste and smell (chemo); and
tactile (mechano). There are also other special sense receptors, including thermo
and noxious receptors. The focus of this study is on photoreceptors, sound
receptors and odorant-receptors because the transduction mechanisms of these
receptors are explained biochemically and understood by a common physical
principle; these biochemical models are well known in neuroscience. The following
notable problems are inherent in these biochemical models: the cGMP ionophore
model of the vertebrate photoreceptor cannot explain the fast photo-response
(~msec); the tip links connection model of stereocilia in the basilar membrane
for opening the K(+) channel on the tip of a hair has difficulty explaining the
high frequency vibration of hair cells without a damping of the oscillation, and
the odorant shape-specific receptor model for olfactory transduction has
difficulty in discriminating the minute differences among similar fragrant smells
of essential oils with different molecular shapes. These difficulties might arise
from a lack of the physical sense when the transduction models were proposed.
This article will reconsider these problems and propose rational models for
visual, olfactory and auditory transduction.
PMID- 27493559
TI - A topological study of gravity free-surface waves generated by bluff bodies using
the method of steepest descents.
AB - The standard analytical approach for studying steady gravity free-surface waves
generated by a moving body often relies upon a linearization of the physical
geometry, where the body is considered asymptotically small in one or several of
its dimensions. In this paper, a methodology that avoids any such geometrical
simplification is presented for the case of steady-state flows at low speeds. The
approach is made possible through a reduction of the water-wave equations to a
complex-valued integral equation that can be studied using the method of steepest
descents. The main result is a theory that establishes a correspondence between
different bluff-bodied free-surface flow configurations, with the topology of the
Riemann surface formed by the steepest descent paths. Then, when a geometrical
feature of the body is modified, a corresponding change to the Riemann surface is
observed, and the resultant effects to the water waves can be derived. This
visual procedure is demonstrated for the case of two-dimensional free-surface
flow past a surface-piercing ship and over an angled step in a channel.
PMID- 27493556
TI - The C-terminal periplasmic domain of MotB is responsible for load-dependent
control of the number of stators of the bacterial flagellar motor.
AB - The bacterial flagellar motor is made of a rotor and stators. In Salmonella it is
thought that about a dozen MotA/B complexes are anchored to the peptidoglycan
layer around the motor through the C-terminal peptidoglycan-binding domain of
MotB to become active stators as well as proton channels. MotB consists of 309
residues, forming a single transmembrane helix (30-50), a stalk (51-100) and a C
terminal peptidoglycan-binding domain (101-309). Although the stalk is
dispensable for torque generation by the motor, it is required for efficient
motor performance. Residues 51 to 72 prevent premature proton leakage through the
proton channel prior to stator assembly into the motor. However, the role of
residues 72-100 remains unknown. Here, we analyzed the torque-speed relationship
of the MotB(Delta72-100) motor. At a low speed near stall, this mutant motor
produced torque at the wild-type level. Unlike the wild-type motor, however,
torque dropped off drastically by slight decrease in external load and then
showed a slow exponential decay over a wide range of load by its further
reduction. Since it is known that the stator is a mechano-sensor and that the
number of active stators changes in a load-dependent manner, we interpreted this
unusual torque-speed relationship as anomaly in load-dependent control of the
number of active stators. The results suggest that residues 72-100 of MotB is
required for proper load-dependent control of the number of active stators around
the rotor.
PMID- 27493560
TI - Nonlinear stratospheric variability: multifractal de-trended fluctuation analysis
and singularity spectra.
AB - Characterizing the stratosphere as a turbulent system, temporal fluctuations
often show different correlations for different time scales as well as
intermittent behaviour that cannot be captured by a single scaling exponent. In
this study, the different scaling laws in the long-term stratospheric variability
are studied using multifractal de-trended fluctuation analysis (MF-DFA). The
analysis is performed comparing four re-analysis products and different
realizations of an idealized numerical model, isolating the role of topographic
forcing and seasonal variability, as well as the absence of climate
teleconnections and small-scale forcing. The Northern Hemisphere (NH) shows a
transition of scaling exponents for time scales shorter than about 1 year, for
which the variability is multifractal and scales in time with a power law
corresponding to a red spectrum, to longer time scales, for which the variability
is monofractal and scales in time with a power law corresponding to white noise.
Southern Hemisphere (SH) variability also shows a transition at annual scales.
The SH also shows a narrower dynamical range in multifractality than the NH, as
seen in the generalized Hurst exponent and in the singularity spectra. The
numerical integrations show that the models are able to reproduce the low
frequency variability but are not able to fully capture the shorter term
variability of the stratosphere.
PMID- 27493561
TI - H2 production by the photocatalytic reforming of cellulose and raw biomass using
Ni, Pd, Pt and Au on titania.
AB - Here, we report a method for sustainable hydrogen production using sunlight and
biomass. It is shown that cellulose can be photoreformed to produce hydrogen,
even in solid form, by use of metal-loaded titania photocatalysts. The
experiments performed verified that the process is enabled by initial hydrolysis
via glucose, which itself is shown to be efficiently converted to produce
hydrogen by photocatalysis. Importantly, it is shown that not only precious
metals such as Pt, Pd and Au can be used as the metal component, but also much
more economic and less environmentally damaging Ni is effective. Even more
importantly, we show for the first time, to the best our knowledge, that fescue
grass as raw biomass can be effective for hydrogen production without significant
pre-treatment. This provides additional benefits for the efficiency of biomass
hydrogen production, because fewer processing steps for the raw material are
required than in the production of purer forms of cellulose, for example.
PMID- 27493562
TI - High-frequency homogenization for travelling waves in periodic media.
AB - We consider high-frequency homogenization in periodic media for travelling waves
of several different equations: the wave equation for scalar-valued waves such as
acoustics; the wave equation for vector-valued waves such as electromagnetism and
elasticity; and a system that encompasses the Schrodinger equation. This
homogenization applies when the wavelength is of the order of the size of the
medium periodicity cell. The travelling wave is assumed to be the sum of two
waves: a modulated Bloch carrier wave having crystal wavevector [Formula: see
text] and frequency omega1 plus a modulated Bloch carrier wave having crystal
wavevector [Formula: see text] and frequency omega2. We derive effective
equations for the modulating functions, and then prove that there is no coupling
in the effective equations between the two different waves both in the scalar and
the system cases. To be precise, we prove that there is no coupling unless
omega1=omega2 and [Formula: see text] where Lambda=(lambda1lambda2...lambda d )
is the periodicity cell of the medium and for any two vectors [Formula: see text]
the product a?b is defined to be the vector (a1b1,a2b2,...,adbd ). This last
condition forces the carrier waves to be equivalent Bloch waves meaning that the
coupling constants in the system of effective equations vanish. We use two-scale
analysis and some new weak-convergence type lemmas. The analysis is not at the
same level of rigour as that of Allaire and co-workers who use two-scale
convergence theory to treat the problem, but has the advantage of simplicity
which will allow it to be easily extended to the case where there is degeneracy
of the Bloch eigenvalue.
PMID- 27493563
TI - Influence of dopant substitution mechanism on catalytic properties within
hierarchical architectures.
AB - A range of hierarchically porous (HP) AlPO-5 catalysts, with isomorphously
substituted transition metal ions, have been synthesized using an organosilane as
a soft template. By employing a range of structural and spectroscopic
characterization protocols, the properties of the dopant-substituted species
within the HP architectures have been carefully evaluated. The resulting nature
of the active site is shown to have a direct impact on the ensuing catalytic
properties in the liquid-phase Beckmann rearrangement of cyclic ketones.
PMID- 27493564
TI - Whispering Bloch modes.
AB - We investigate eigenvalue problems for the planar Helmholtz equation in open
systems with a high order of rotational symmetry. The resulting solutions have
similarities with the whispering gallery modes exploited in photonic micro
resonators and elsewhere, but unlike these do not necessarily require a
surrounding material boundary, with confinement instead resulting from the
geometry of a series of inclusions arranged in a ring. The corresponding fields
exhibit angular quasi-periodicity reminiscent of Bloch waves, and hence we refer
to them as whispering Bloch modes (WBMs). We show that if the geometry of the
system is slightly perturbed such that the rotational symmetry is broken, modes
with asymmetric field patterns can be observed, resulting in field enhancement
and other potentially desirable effects. We investigate the WBMs of two specific
geometries first using expansion methods and then by applying a two-scale
asymptotic scheme.
PMID- 27493565
TI - Movement of a finite body in channel flow.
AB - A body of finite size is moving freely inside, and interacting with, a channel
flow. The description of this unsteady interaction for a comparatively dense thin
body moving slowly relative to flow at medium-to-high Reynolds number shows that
an inviscid core problem with vorticity determines much, but not all, of the
dominant response. It is found that the lift induced on a body of length
comparable to the channel width leads to differences in flow direction upstream
and downstream on the body scale which are smoothed out axially over a longer
viscous length scale; the latter directly affects the change in flow directions.
The change is such that in any symmetric incident flow the ratio of slopes is
found to be [Formula: see text], i.e. approximately 0.900969, independently of
Reynolds number, wall shear stresses and velocity profile. The two axial scales
determine the evolution of the body and the flow, always yielding instability.
This unusual evolution and linear or nonlinear instability mechanism arise
outside the conventional range of flow instability and are influenced
substantially by the lateral positioning, length and axial velocity of the body.
PMID- 27493566
TI - North error estimation based on solar elevation errors in the third step of sky
polarimetric Viking navigation.
AB - The theory of sky-polarimetric Viking navigation has been widely accepted for
decades without any information about the accuracy of this method. Previously, we
have measured the accuracy of the first and second steps of this navigation
method in psychophysical laboratory and planetarium experiments. Now, we have
tested the accuracy of the third step in a planetarium experiment, assuming that
the first and second steps are errorless. Using the fists of their outstretched
arms, 10 test persons had to estimate the elevation angles (measured in numbers
of fists and fingers) of black dots (representing the position of the occluded
Sun) projected onto the planetarium dome. The test persons performed 2400
elevation estimations, 48% of which were more accurate than +/-1 degrees . We
selected three test persons with the (i) largest and (ii) smallest elevation
errors and (iii) highest standard deviation of the elevation error. From the
errors of these three persons, we calculated their error function, from which the
North errors (the angles with which they deviated from the geographical North)
were determined for summer solstice and spring equinox, two specific dates of the
Viking sailing period. The range of possible North errors DeltaomegaN was the
lowest and highest at low and high solar elevations, respectively. At high
elevations, the maximal DeltaomegaN was 35.6 degrees and 73.7 degrees at summer
solstice and 23.8 degrees and 43.9 degrees at spring equinox for the best and
worst test person (navigator), respectively. Thus, the best navigator was twice
as good as the worst one. At solstice and equinox, high elevations occur the most
frequently during the day, thus high North errors could occur more frequently
than expected before. According to our findings, the ideal periods for sky
polarimetric Viking navigation are immediately after sunrise and before sunset,
because the North errors are the lowest at low solar elevations.
PMID- 27493567
TI - Predicting the secondary dynamic mode interference phenomenon in thermoacoustic
instability control.
AB - This paper brings a novel mathematical perspective in assessing the rise of the
secondary dynamic modes to prominence during the suppression of thermoacoustic
instability. This phenomenon is observed by many earlier investigators; however,
without a complete analytical reasoning. We consider a Rijke tube with both a
passive Helmholtz resonator and an active feedback control to suppress
instabilities. The core dynamics is represented as a linear time-invariant
multiple time-delay system of neutral type. Parametric stability of the resulting
infinite-dimensional dynamics is investigated using a recent analytical tool:
cluster treatment of characteristic roots paradigm. This tool reveals the
stability outlook of such systems exhaustively and non-conservatively in the
parameter space of the system. First, we examine the stability with and without
the Helmholtz resonator. We then select an unstable operation for the resonator
mounted Rijke tube, impose a time-delayed integral feedback control over it and
reveal the stabilizing controller parameters using the cluster treatment of
characteristic roots methodology. When high control gains are inappropriately
selected, the new analytical procedure declares how the secondary dynamic modes
of the system exhibit instability although the initially unstable mode is now
stabilized. All of these stability assessments are cross-validated using
experimental results from a laboratory-scale Rijke tube set-up.
PMID- 27493568
TI - Evidence of protein-free homology recognition in magnetic bead force-extension
experiments.
AB - Earlier theoretical studies have proposed that the homology-dependent pairing of
large tracts of dsDNA may be due to physical interactions between homologous
regions. Such interactions could contribute to the sequence-dependent pairing of
chromosome regions that may occur in the presence or the absence of double-strand
breaks. Several experiments have indicated the recognition of homologous
sequences in pure electrolytic solutions without proteins. Here, we report single
molecule force experiments with a designed 60 kb long dsDNA construct; one end
attached to a solid surface and the other end to a magnetic bead. The 60 kb
constructs contain two 10 kb long homologous tracts oriented head to head, so
that their sequences match if the two tracts fold on each other. The distance
between the bead and the surface is measured as a function of the force applied
to the bead. At low forces, the construct molecules extend substantially less
than normal, control dsDNA, indicating the existence of preferential interaction
between the homologous regions. The force increase causes no abrupt but
continuous unfolding of the paired homologous regions. Simple semi
phenomenological models of the unfolding mechanics are proposed, and their
predictions are compared with the data.
PMID- 27493569
TI - Loose powder detection and surface characterization in selective laser sintering
via optical coherence tomography.
AB - Defects produced during selective laser sintering (SLS) are difficult to non
destructively detect after build completion without the use of X-ray-based
methods. Overcoming this issue by assessing integrity on a layer-by-layer basis
has become an area of significant interest for users of SLS apparatus. Optical
coherence tomography (OCT) is used in this study to detect surface texture and
sub-surface powder, which is un-melted/insufficiently sintered, is known to be a
common cause of poor part integrity and would prevent the use of SLS where
applications dictate assurance of defect-free parts. To demonstrate the
capability of the instrument and associated data-processing algorithms, samples
were built with graduated porosities which were embedded in fully dense regions
in order to simulate defective regions. Simulated in situ measurements were then
correlated with the process parameters used to generate variable density regions.
Using this method, it is possible to detect loose powder and differentiate
between densities of +/-5% at a sub-surface depth of approximately 300 MUm. In
order to demonstrate the value of OCT as a surface-profiling technique, surface
texture datasets are compared with focus variation microscopy. Comparable results
are achieved after a spatial bandwidth- matching procedure.
PMID- 27493570
TI - Constitutive equation of friction based on the subloading-surface concept.
AB - The subloading-friction model is capable of describing static friction, the
smooth transition from static to kinetic friction and the recovery to static
friction after sliding stops or sliding velocity decreases. This causes a
negative rate sensitivity (i.e. a decrease in friction resistance with increasing
sliding velocity). A generalized subloading-friction model is formulated in this
article by incorporating the concept of overstress for viscoplastic sliding
velocity into the subloading-friction model to describe not only negative rate
sensitivity but also positive rate sensitivity (i.e. an increase in friction
resistance with increasing sliding velocity) at a general sliding velocity
ranging from quasi-static to impact sliding. The validity of the model is
verified by numerical experiments and comparisons with test data obtained from
friction tests using a lubricated steel specimen.
PMID- 27493571
TI - Johnson-Kendall-Roberts adhesive contact for a toroidal indenter.
AB - The unilateral axisymmetric frictionless adhesive contact problem for a toroidal
indenter and an elastic half-space is considered in the framework of the Johnson
Kendall-Roberts theory. In the case of a semi-fixed annular contact area, when
one of the contact radii is fixed, while the other varies during indentation, we
obtain the asymptotic solution of the adhesive contact problem based on the
solution of the corresponding unilateral non-adhesive contact problem. In
particular, the adhesive contact problem for Barber's concave indenter is
considered in detail. In the case when both contact radii are variable, we
construct the leading-order asymptotic solution for a narrow annular contact
area. It is found that for a v-shaped generalized toroidal indenter, the pull-off
force is independent of the elastic properties of the indented solid.
PMID- 27493572
TI - Unidirectional invisibility and non-reciprocal transmission in two and three
dimensions.
AB - We explore the phenomenon of unidirectional invisibility in two dimensions,
examine its optical realizations and discuss its three-dimensional
generalization. In particular, we construct an infinite class of unidirectionally
invisible optical potentials that describe the scattering of normally incident
transverse electric waves by an infinite planar slab with refractive-index
modulations along both the normal directions to the electric field. A by-product
of this investigation is a demonstration of non-reciprocal transmission in two
dimensions. To elucidate this phenomenon, we state and prove a general
reciprocity theorem that applies to quantum scattering theory of real and complex
potentials in two and three dimensions.
PMID- 27493573
TI - Superalgebraically convergent smoothly windowed lattice sums for doubly periodic
Green functions in three-dimensional space.
AB - This work, part I in a two-part series, presents: (i) a simple and highly
efficient algorithm for evaluation of quasi-periodic Green functions, as well as
(ii) an associated boundary-integral equation method for the numerical solution
of problems of scattering of waves by doubly periodic arrays of scatterers in
three-dimensional space. Except for certain 'Wood frequencies' at which the quasi
periodic Green function ceases to exist, the proposed approach, which is based on
smooth windowing functions, gives rise to tapered lattice sums which converge
superalgebraically fast to the Green function-that is, faster than any power of
the number of terms used. This is in sharp contrast to the extremely slow
convergence exhibited by the lattice sums in the absence of smooth windowing.
(The Wood-frequency problem is treated in part II.) This paper establishes
rigorously the superalgebraic convergence of the windowed lattice sums. A variety
of numerical results demonstrate the practical efficiency of the proposed
approach.
PMID- 27493574
TI - The dynamic generalization of the Eshelby inclusion problem and its static limit.
AB - The dynamic generalization of the celebrated Eshelby inclusion with
transformation strain is the (subsonically) self-similarly expanding ellipsoidal
inclusion starting from the zero dimension. The solution of the governing system
of partial differential equations was obtained recently by Ni & Markenscoff (In
press. J. Mech. Phys. Solids (doi:10.1016/j.jmps.2016.02.025)) on the basis of
the Radon transformation, while here an alternative method is presented. In the
self-similarly expanding motion, the Eshelby property of constant constrained
strain is valid in the interior domain of the expanding ellipsoid where the
particle velocity vanishes (lacuna). The dynamic Eshelby tensor is obtained in
integral form. From it, the static Eshelby tensor is obtained by a limiting
procedure, as the axes' expansion velocities tend to zero and time to infinity,
while their product is equal to the length of the static axis. This makes the
Eshelby problem the limit of its dynamic generalization.
PMID- 27493575
TI - Surface plasmon resonances of arbitrarily shaped nanometallic structures in the
small-screening-length limit.
AB - According to the hydrodynamic Drude model, surface plasmon resonances of metallic
nanostructures blueshift owing to the non-local response of the metal's electron
gas. The screening length characterizing the non-local effect is often small
relative to the overall dimensions of the metallic structure, which enables us to
derive a coarse-grained non-local description using matched asymptotic
expansions; a perturbation theory for the blueshifts of arbitrary-shaped
nanometallic structures is then developed. The effect of non-locality is not
always a perturbation and we present a detailed analysis of the 'bonding' modes
of a dimer of nearly touching nanowires where the leading-order eigenfrequencies
and eigenmode distributions are shown to be a renormalization of those predicted
assuming a local metal permittivity.
PMID- 27493576
TI - Global defect topology in nematic liquid crystals.
AB - We give the global homotopy classification of nematic textures for a general
domain with weak anchoring boundary conditions and arbitrary defect set in terms
of twisted cohomology, and give an explicit computation for the case of knotted
and linked defects in [Formula: see text], showing that the distinct homotopy
classes have a 1-1 correspondence with the first homology group of the branched
double cover, branched over the disclination loops. We show further that the
subset of those classes corresponding to elements of order 2 in this group has
representatives that are planar and characterize the obstruction for other
classes in terms of merons. The planar textures are a feature of the global
defect topology that is not reflected in any local characterization. Finally, we
describe how the global classification relates to recent experiments on nematic
droplets and how elements of order 4 relate to the presence of tau lines in
cholesterics.
PMID- 27493577
TI - Point vortex interactions on a toroidal surface.
AB - Owing to non-constant curvature and a handle structure, it is not easy to imagine
intuitively how flows with vortex structures evolve on a toroidal surface
compared with those in a plane, on a sphere and a flat torus. In order to
cultivate an insight into vortex interactions on this manifold, we derive the
evolution equation for N-point vortices from Green's function associated with the
Laplace-Beltrami operator there, and we then formulate it as a Hamiltonian
dynamical system with the help of the symplectic geometry and the uniformization
theorem. Based on this Hamiltonian formulation, we show that the 2-vortex problem
is integrable. We also investigate the point vortex equilibria and the motion of
two-point vortices with the strengths of the same magnitude as one of the
fundamental vortex interactions. As a result, we find some characteristic
interactions between point vortices on the torus. In particular, two identical
point vortices can be locally repulsive under a certain circumstance.
PMID- 27493578
TI - A non-classical Mindlin plate model incorporating microstructure, surface energy
and foundation effects.
AB - A non-classical model for a Mindlin plate resting on an elastic foundation is
developed in a general form using a modified couple stress theory, a surface
elasticity theory and a two-parameter Winkler-Pasternak foundation model. It
includes all five kinematic variables possible for a Mindlin plate. The equations
of motion and the complete boundary conditions are obtained simultaneously
through a variational formulation based on Hamilton's principle, and the
microstructure, surface energy and foundation effects are treated in a unified
manner. The newly developed model contains one material length-scale parameter to
describe the microstructure effect, three surface elastic constants to account
for the surface energy effect, and two foundation parameters to capture the
foundation effect. The current non-classical plate model reduces to its classical
elasticity-based counterpart when the microstructure, surface energy and
foundation effects are all suppressed. In addition, the new model includes the
Mindlin plate models considering the microstructure dependence or the surface
energy effect or the foundation influence alone as special cases, recovers the
Kirchhoff plate model incorporating the microstructure, surface energy and
foundation effects, and degenerates to the Timoshenko beam model including the
microstructure effect. To illustrate the new Mindlin plate model, the static
bending and free vibration problems of a simply supported rectangular plate are
analytically solved by directly applying the general formulae derived.
PMID- 27493579
TI - Interaction between mean flow and turbulence in two dimensions.
AB - This short note is written to call attention to an analytic approach to the
interaction of developed turbulence with mean flows of simple geometry (jets and
vortices). It is instructive to compare cases in two and three dimensions and see
why the former are solvable and the latter are not (yet). We present the
analytical solutions for two-dimensional mean flows generated by an inverse
turbulent cascade on a sphere and in planar domains of different aspect ratios.
These solutions are obtained in the limit of small friction when the flow is
strong while turbulence can be considered weak and treated perturbatively. I then
discuss when these simple solutions can be realized and when more complicated
flows may appear instead. The next step of describing turbulence statistics
inside a flow and directions of possible future progress are briefly discussed at
the end.
PMID- 27493580
TI - A physical model for low-frequency electromagnetic induction in the near field
based on direct interaction between transmitter and receiver electrons.
AB - A physical model of electromagnetic induction is developed which relates directly
the forces between electrons in the transmitter and receiver windings of
concentric coaxial finite coils in the near-field region. By applying the
principle of superposition, the contributions from accelerating electrons in
successive current loops are summed, allowing the peak-induced voltage in the
receiver to be accurately predicted. Results show good agreement between theory
and experiment for various receivers of different radii up to five times that of
the transmitter. The limitations of the linear theory of electromagnetic
induction are discussed in terms of the non-uniform current distribution caused
by the skin effect. In particular, the explanation in terms of electromagnetic
energy and Poynting's theorem is contrasted with a more direct explanation based
on variable filament induction across the conductor cross section. As the direct
physical model developed herein deals only with forces between discrete current
elements, it can be readily adapted to suit different coil geometries and is
widely applicable in various fields of research such as near-field
communications, antenna design, wireless power transfer, sensor applications and
beyond.
PMID- 27493581
TI - Origami mechanical metamaterials based on the Miura-derivative fold patterns.
AB - This paper presents two new types of origami-inspired mechanical metamaterials
based on the Miura-derivative fold patterns that consist of non-identical
parallelogram facets. The analytical models to predict dimension changes and
deformation kinematics of the proposed metamaterials are developed. Furthermore,
by modelling the creases as revolute hinges with certain rotational spring
constants, we derived analytical models for stretching and bulk moduli. The
analytical models are validated through finite-element simulation results.
Numerical examples reveal that the proposed metamaterials possess some intriguing
properties, including negative Poisson's ratios and bulk modulus. The work
presented in this paper can provide a highly flexible framework for the design of
versatile tunable mechanical metamaterials.
PMID- 27493582
TI - Turbulent jet manipulation using two unsteady azimuthally separated radial
minijets.
AB - The active manipulation of a turbulent round jet is experimentally investigated
based on the injection of two radial unsteady minijets, prior to the issue of the
main jet. The parametric study is conducted for the mass flow ratio Cm of the
minijets to the main jet, and the ratio fe/f0 of the minijet frequency to the
preferred-mode frequency of the main jet. It is found that the decay rate of the
jet centreline mean velocity could be greatly increased if the two minijets are
separated azimuthally by an angle theta=60 degrees , instead of by theta=180
degrees . This increase is a consequence of the flapping motion of the jet
column, and the formation process and generation mechanism of this flapping
motion are unveiled by careful analysis of the experimental data.
PMID- 27493583
TI - A generalized optimization principle for asymmetric branching in fluidic
networks.
AB - When applied to a branching network, Murray's law states that the optimal
branching of vascular networks is achieved when the cube of the parent channel
radius is equal to the sum of the cubes of the daughter channel radii. It is
considered integral to understanding biological networks and for the biomimetic
design of artificial fluidic systems. However, despite its ubiquity, we
demonstrate that Murray's law is only optimal (i.e. maximizes flow conductance
per unit volume) for symmetric branching, where the local optimization of each
individual channel corresponds to the global optimum of the network as a whole.
In this paper, we present a generalized law that is valid for asymmetric
branching, for any cross-sectional shape, and for a range of fluidic models. We
verify our analytical solutions with the numerical optimization of a bifurcating
fluidic network for the examples of laminar, turbulent and non-Newtonian fluid
flows.
PMID- 27493584
TI - Transient effects of drying creep in nanoporous solids: understanding the effects
of nanoscale energy barriers.
AB - The Pickett effect is the phenomenon of creep enhancement during transient
drying. It has been observed for many nanoporous solids, including concrete, wood
and Kevlar. While the existing micromechanical models can partially explain this
effect, they have yet to consider nanoscale dynamic effects of water in
nanopores, which are believed to be of paramount importance. Here, we examine how
creep deformations in a slit pore are accelerated by the motion of water due to
drying forces using coarse-grained molecular dynamics simulations. We find that
the drying that drives water flow in the nanopores lowers both the activation
energy of pore walls sliding past one another and the apparent viscosity of
confined water molecules. This lowering can be captured with an analytical
Arrhenius relationship accounting for the role of water flow in overcoming the
energy barriers. Notably, we use this model and simulation results to demonstrate
that the drying creep strain is not linearly dependent on the applied creep
stress at the nanopore level. Our findings establish the scaling relationships
that explain how the creep driving force, drying force and fluid properties are
related. Thus, we establish the nanoscale origins of the Pickett effect and
provide strategies for minimizing the additional displacements arising from this
effect.
PMID- 27493585
TI - It's Not Business, It's Personal: Implicit Religion in the Corporate Personhood
Debate.
AB - Debate surrounding the United States Supreme Court's 2010 decision in Citizens
United v. FEC is ostensibly about the legal rights of corporations. However, I
argue that the debate about corporate personhood is infused with religious
concerns, rooted in the Protestant Reformation, about the proper identification
of agentive subjects and the consequences of misidentification for human
personhood. Focusing on the language used by opponents and defenders in the
popular media, I show how both sides are animated by Protestant notions of human
agency and share similar anxieties about the threats to that agency posed by
abstract corporate or governmental entities. Attending to this fundamentally
religious dimension not only improves our understanding of the moral stakes in
the debate over corporations' legal rights but it also illuminates the implicit
religious underpinnings of American political discourse.
PMID- 27493586
TI - Patients' perceptions of the meaning of good care in surgical care: a grounded
theory study.
AB - BACKGROUND: Patients in surgical care have reported a fear of being discharged
prior to sufficient recovery and a lack of control of their situation.
Establishing the patient-nurse relationship is essential in the context of the
care. The Swedish National Board of Health and Welfare has established indicators
for good care for comparison, evaluation and improvement of the quality of the
health care system. These indicators are knowledge-based, appropriate, safe,
effective and equal health care, as well as care within a reasonable time and
patient-centred care. Current core competence in nursing education include
quality improvement, patient-centred care, teamwork and collaboration, using
evidence-based practice, safety and informatics. This study investigates
patients' perceptions of the meaning of good care in inpatient surgical care.
METHODS: Grounded theory according to Charmaz was chosen as the study design.
Interviews were conducted with 13 patients from six surgical wards in the south
of Sweden in 2014-2015. RESULTS: The results showed that patients in surgical
care perceived good care as being safe, as they were vulnerable and anxious. This
could be achieved through accessible care, reliable care, caring attitudes and
participating in one's own care. Patient participation was achieved by
information and education and the possibility to affect their care. CONCLUSION:
Patients need safety to experience good care. Caring attitudes and patient
participation can be attained through patient-centred care. Bedside handover can
improve patients' perceptions of accessible care and reliable care and can
increase patient participation. Continuously maintaining competence and using
evidence-based practice are needed to achieve reliable care.
PMID- 27493587
TI - Nasal inflammation and its response to local glucocorticoid regular treatment in
patients with persistent non-allergic rhinitis: a pilot study.
AB - BACKGROUND: The pathogenesis of non-allergic rhinitis (NAR) is still largely
unknown. Furthermore, it is unclear whether there is a correlation between the
effect of nasal glucocorticoids on nasal inflammation and on nasal symptoms and
quality of life. METHODS: In this pilot study we recruited 12 healthy subjects
and 24 patients with recently diagnosed persistent NAR [12 untreated and 12 under
regular treatment with nasal fluticasone furoate (two sprays of 27.5 MUg each in
each nostril once daily, total daily dose = 110 MUg) for at least 20 days]. Each
subject filled a mini rhinoconjunctivitis quality of life questionnaire (mini
RQLQ). Nasal scrapings were obtained from each subject and used to prepare slides
for Diff-Quik and immunocytochemical staining for inflammatory and epithelial
cells count, MUC5AC expression and the general pro-inflammatory transcription
factor nuclear factor kB (NF-kB) activation. RESULTS: The nasal score of the mini
RQLQ, the number of nasal inflammatory cells (neutrophils, eosinophils) and the
number of goblet cells are significantly higher in untreated patients with
persistent NAR compared with control subjects and treated NAR patients. The
percentage of MUC5AC+ nasal epithelial cells is significantly increased in
untreated patients with persistent NAR compared with the control subjects (41.8
+/- 6.4 vs 22.3 +/- 4.8, respectively; p = 0.0403) without significant
differences between control subjects and patients with persistent NAR on regular
fluticasone furoate treatment (33.9 +/- 5.0 %; p = 0.0604) nor between the 2
groups of persistent NAR subjects (p = 0.3260). The number of cytosolic and/or
nuclear p65+ nasal epithelial and inflammatory cells was not significantly
different between the three groups. CONCLUSIONS: Patients with persistent
untreated NAR, compared with normal control subjects and patients with persistent
NAR under regular treatment with nasal fluticasone furoate by at least 20 days,
have more nasal symptoms, worst quality of life and an increased number of nasal
inflammatory cells (neutrophils, eosinophils), goblet cells and MUC5AC+ nasal
epithelial cells. This nasal inflammation seems unrelated to NF-kB activation.
PMID- 27493588
TI - Recognizing millions of consistently unidentified spectra across hundreds of
shotgun proteomics datasets.
AB - Mass spectrometry (MS) is the main technology used in proteomics approaches.
However, on average 75% of spectra analysed in an MS experiment remain
unidentified. We propose to use spectrum clustering at a large-scale to shed a
light on these unidentified spectra. PRoteomics IDEntifications database (PRIDE)
Archive is one of the largest MS proteomics public data repositories worldwide.
By clustering all tandem MS spectra publicly available in PRIDE Archive, coming
from hundreds of datasets, we were able to consistently characterize three
distinct groups of spectra: 1) incorrectly identified spectra, 2) spectra
correctly identified but below the set scoring threshold, and 3) truly
unidentified spectra. Using a multitude of complementary analysis approaches, we
were able to identify less than 20% of the consistently unidentified spectra. The
complete spectrum clustering results are available through the new version of the
PRIDE Cluster resource (http://www.ebi.ac.uk/pride/cluster). This resource is
intended, among other aims, to encourage and simplify further investigation into
these unidentified spectra.
PMID- 27493589
TI - Leptospira Exposure and Patients with Liver Diseases: A Case-Control
Seroprevalence Study.
AB - The seroepidemiology of Leptospira infection in patients suffering from liver
disease has been poorly studied. Information about risk factors associated with
infection in liver disease patients may help in the optimal planning of
preventive measures. We sought to determine the association of Leptospira IgG
seroprevalence and patients with liver diseases, and to determine the
characteristics of the patients with Leptospira exposure. We performed a case
control study of 75 patients suffering from liver diseases and 150 age- and
gender-matched control subjects. Diagnoses of liver disease included liver
cirrhosis, steatosis, chronic hepatitis, acute hepatitis, and amoebic liver
abscess. Sera of participants were analyzed for the presence of anti- Leptospira
IgG antibodies using a commercially available enzyme immunoassay. Anti-Leptospira
IgG antibodies were found in 17 (22.7%) of 75 patients and in 15 (10.0%) of 150
control subjects (OR = 2.32; 95% CI: 1.09-4.94; P=0.03). This is the first age-
and gender-matched case control study about Leptospira seroprevalence in patients
with liver diseases. Results indicate that Leptospira infection is associated
with chronic and acute liver diseases. Results warrants for additional studies on
the role of Leptospira exposure in chronic liver disease.
PMID- 27493590
TI - IL-2 Expression and T lymphocyte Phenotyping in Young Children Suffering from
Upper Respiratory Tract Infection with Streptococcus Pyogenes.
AB - T cells are components of adaptive immunity and are involved in the resolution of
respiratory infections, which are a major cause of morbidity and mortality in
young children worldwide. Activation and differentiation of T cells is given
mostly by the cytokine IL-2. This study aimed to determine the phenotype of T
cells and IL-2 expression in children suffering from upper respiratory tract
infection with Streptococcus pyogenes (S. pyogenes). For this purpose, IL-2
expression at its gene and protein levels and quantitation of CD4(+) and CD8(+) T
lymphocytes were assessed in children aged 0-5 years old suffering from upper
respiratory tract infection with S. pyogenes and healthy children of the same
age. Children with S. pyogenes infection had a higher expression of IL-2 gene and
a lower level of this cytokine expression at protein level than healthy children.
The numbers of CD4(+) T lymphocytes were similar among the groups. In contrast,
difference in the numbers of CD8(+) T lymphocytes among the groups was found. We
conclude that infections by S. pyogenes in young children lead to an increased
expression of IL-2 mRNA.
PMID- 27493591
TI - Accessory Inferior Sulci of the Liver in an Afro-Caribbean Population.
AB - INTRODUCTION: There have been no previous reports on the anatomic variations that
exist on inferior surface of the liver in Caribbean populations. This information
is important to optimize radiology and hepatobiliary surgical services in the
region. METHODS: Two investigators independently observed 69 cadaveric
dissections over five years and described the variations in surface anatomy.
RESULTS: In this population 88% of cadaveric livers had conventional hepatic
surface anatomy. However, 12% had accessory sulci present on the visceral surface
of the liver, with a 7:1 male preponderance. When present, there was 100%
correlation between the presence of Rouviere's sulcus and the right branch of
portal pedicle. CONCLUSION: Abnormal surface anatomy is present in 12% of
unselected specimens in this Caribbean population. Interventional radiologists
and hepatobiliary surgeons practicing in the Caribbean must be cognizant of these
differences in order to minimize morbidity during invasive procedures.
PMID- 27493592
TI - Self-rated Health and Internet Addiction in Iranian Medical Sciences Students;
Prevalence, Risk Factors and Complications.
AB - INTRODUCTION: Self-rated health is a brief measure for general health. It is a
comprehensive and sensitive index for prediction of health in future. Due to the
high internet usage in medical students, the current study designed to evaluate
the self-rated health (SRH) in relationship with internet addiction risk factors
in medical students. METHODS: This cross sectional study conducted on 254
students of Qom University of Medical Sciences 2014. Participants selected by two
stage sampling method including stratified and simple random sampling. The
Young's questionnaire of internet addiction and SRH question used for data
collection. Chi-square, t-test, and logistic regression used in data analysis.
RESULTS: More than 79.9% of students reported their general health good and very
good. The student's mean score of general health was higher than the average. In
addition, the prevalence of internet addiction was 28.7%. An inverse significant
correlation observed between SRH and internet addiction score (r=-0.198,
p=0.002). Using internet for Entertainment, using private Email and chat rooms
were the most important predictors of affecting to internet addiction. Moreover,
internet addiction is the most predictors of SRH and increased the odds of bad
SRH. CONCLUSION: The good SRH of medical students was higher than general
population but in health faculty' students were lower than others. Due to the
effect of internet addiction on SRH and increasing trend of internet use in
medical students, as well as low age of participants, attention to psychological
aspects and the job expectancy in future, can effective on increasing the good
SRH.
PMID- 27493594
TI - Focus on Endoscopy.
PMID- 27493593
TI - Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced
Hepatotoxicity in Rats.
AB - Clinical studies have shown that several classes of antibiotics are evidenced in
drug induced liver injury. The combination of amoxicillin with clavulanic acid is
commonly cited in such cases. Accordingly, the present study investigated the
potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil
in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was
hydrodistilled from the aerial parts of Salvia officinalis L. and its
compositional analysis was characterized by Gas chromatography-Mass spectroscopy.
Rats were treated singly or concomitantly with Co-amoxiclav and sage essential
oil for a period of seven days. The major components of sage oil as identified by
GC-MS were 1,8-cineole, beta-pinene, camphor, beta-caryophyllene, alpha-pinene
and alpha-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5%
respectively. The in vivo exposure of rats to Co-amoxiclav resulted in
hepatotoxicity biochemically evidenced by the significant elevation of serum AST,
ALT, ALP, gamma-GT, total bilirubin and histologically conveyed by hydropic,
inflammatory and cholestatic changes in rats' liver. Oxidative stress mediated
the hepatic injury as indicated by the significant escalation in lipid
peroxidation, as well as, the significant depletion of both glutathione level and
glutathione dependent enzymes' activities. The concomitant administration of sage
essential oil with Co-amoxiclav exerted a hepatoprotective effect via inducing an
in vivo antioxidant defense response eventually regressing, to some extent, the
hepatoarchitectural changes induced by Co-amoxiclav. Results suggest that sage
essential oil is a potential candidate for counteracting hepatic injury
associating Co-amoxiclav and this effect is in part related to the complexity of
its chemical composition.
PMID- 27493595
TI - Gastro-Hep News.
PMID- 27493596
TI - A Systematic Review of Factors Associated With Utilization of Monitored
Anesthesia Care for Gastrointestinal Endoscopy.
AB - Utilization of monitored anesthesia care (MAC) for gastrointestinal endoscopy has
increased markedly over the past decade, leading to significant additional health
care expenditures. However, the extent to which certain patient-, provider-, and
facility-level factors lead to MAC utilization is unclear. A systematic review of
13 studies evaluating influential factors associated with MAC utilization for
colonoscopy and/or esophagogastroduodenoscopy was conducted. Multiple studies
revealed significant increases in MAC utilization since the early 2000s, with
substantial regional variation. The most influential patient-related factors
associated with MAC utilization include female sex and diagnostic procedural
indication. Other patient-related factors with weaker associations or conflicting
evidence include older age, comorbidity, higher patient income, and white/non
Hispanic race. The impact of patient substance use and/or prescription medication
use has been minimally studied. The strongest provider- and facility-level
factors associated with MAC use are a surgeon endoscopist and nonhospital site of
service. Other factors with weaker associations include facility endoscopy volume
and endoscopist years of experience. Further qualitative and quantitative health
services research is needed to better understand the root cause of the rising
trend of MAC utilization and to develop policies for encouraging appropriate use
of MAC.
PMID- 27493597
TI - Fecal Microbiota Transplantation for Inflammatory Bowel Disease.
AB - The gut bacterial microbiome, particularly its role in disease and inflammation,
has gained international attention with the successful use of fecal microbiota
transplantation (FMT) in the treatment of Clostridium difficile infection. This
success has led to studies exploring the role of FMT in other conditions,
including inflammatory bowel disease (IBD). Both Crohn's disease and ulcerative
colitis are chronic inflammatory conditions of the gastrointestinal system that
have multifactorial etiologies. A shift in gut microbial composition in
genetically susceptible individuals, an altered immune system, and environmental
factors are all hypothesized to have a role in the pathogenesis of IBD. While
numerous case reports and cohort studies have described the use of FMT in
patients with IBD over the last 2 decades, the development of new sequencing
techniques and results from 2 recent randomized, controlled trials have allowed
for a better understanding of the relationship between the microbiome and the
human host. However, despite these efforts, knowledge remains limited and the
role of FMT in the management of IBD remains uncertain. Further investigation is
necessary before FMT joins the current armamentarium of treatment options in
clinical practice.
PMID- 27493598
TI - Use of a Through-the-Scope Balloon System for Deep Enteroscopy.
PMID- 27493599
TI - Surveillance for Hepatocellular Carcinoma.
PMID- 27493600
TI - The Role of Bariatric Surgery in the Management of Nonalcoholic Steatohepatitis.
PMID- 27493601
TI - Transoral Incisionless Fundoplication for the Treatment of Gastroesophageal
Reflux Disease.
PMID- 27493602
TI - The Transition From Pediatric to Adult Inflammatory Bowel Disease Care.
PMID- 27493603
TI - The Transcription Cofactor Swi6 of the Fusarium graminearum Is Involved in
Fusarium Graminearum Virus 1 Infection-Induced Phenotypic Alterations.
AB - The transcription cofactor Swi6 plays important roles in regulating vegetative
growth and meiosis in Saccharomyces cerevisiae. Functions of Swi6 ortholog were
also characterized in Fusarium graminearum which is one of the devastating plant
pathogenic fungi. Here, we report possible role of FgSwi6 in the interaction
between F. graminearum and Fusarium graminearum virus 1 (FgV1) strain DK21. FgV1
perturbs biological characteristics of host fungi such as vegetative growth,
sporulation, pigmentation, and reduction of the virulence (hypovirulence) of its
fungal host. To characterize function(s) of FgSWI6 gene during FgV1 infection,
targeted deletion, over-expression, and complementation mutants were generated
and further infected successfully with FgV1. Deletion of FgSwi6 led to severe
reduction of vegetative growth even aerial mycelia while over-expression did not
affect any remarkable alteration of phenotype in virus-free isolates. Virus
infected (VI) FgSWI6 deletion isolate exhibited completely delayed vegetative
growth. However, VI FgSWI6 over-expression mutant grew faster than any other VI
isolates. To verify whether these different growth patterns in VI isolates, viral
RNA quantification was carried out using qRT-PCR. Surprisingly, viral RNA
accumulations in VI isolates were similar regardless of introduced mutations.
These results provide evidence that FgSWI6 might play important role(s) in FgV1
induced phenotype alteration such as delayed vegetative growth.
PMID- 27493604
TI - Epidemiology and Control of Strawberry Bacterial Angular Leaf Spot Disease Caused
by Xanthomonas fragariae.
AB - Strawberry bacterial angular leaf spot (ALS) disease, caused by Xanthomonas
fragariae has become increasingly problematic in the strawberry agro-industry.
ALS causes small angular water-soaked lesions to develop on the abaxial leaf
surface. Studies reported optimum temperature conditions for X. fragariae are 20
degrees C and the pathogen suffers mortality above 32 degrees C. However, at the
nursery stage, disease symptoms have been observed under high temperature
conditions. In the present study, results showed X. fragariae transmission was
via infected maternal plants, precipitation, and sprinkler irrigation systems.
Systemic infections were detected using X. fragariae specific primers 245A/B and
295A/B, where 300-bp and 615-bp were respectively amplified. During the nursery
stage (from May to August), the pathogen was PCR detected only in maternal
plants, but not in soil or irrigation water through the nursery stage. During the
cultivation period, from September to March, the pathogen was detected in
maternal plants, progeny, and soil, but not in water. Additionally, un-infected
plants, when planted with infected plants were positive for X. fragariae via PCR
at the late cultivation stage. Chemical control for X. fragariae with oxolinic
acid showed 87% control effects against the disease during the nursery period, in
contrast to validamycin-A, which exhibited increased efficacy against the disease
during the cultivation stage (control effect 95%). To our knowledge, this is the
first epidemiological study of X. fragariae in Korean strawberry fields.
PMID- 27493605
TI - Visual Analysis for Detection and Quantification of Pseudomonas cichorii Disease
Severity in Tomato Plants.
AB - Pathogen infection in plants induces complex responses ranging from gene
expression to metabolic processes in infected plants. In spite of many studies on
biotic stress-related changes in host plants, little is known about the metabolic
and phenotypic responses of the host plants to Pseudomonas cichorii infection
based on image-based analysis. To investigate alterations in tomato plants
according to disease severity, we inoculated plants with different cell densities
of P. cichorii using dipping and syringe infiltration methods. High-dose inocula
(>= 10(6) cfu/ml) induced evident necrotic lesions within one day that
corresponded to bacterial growth in the infected tissues. Among the chlorophyll
fluorescence parameters analyzed, changes in quantum yield of PSII (PhiPSII) and
non-photochemical quenching (NPQ) preceded the appearance of visible symptoms,
but maximum quantum efficiency of PSII (Fv/Fm) was altered well after symptom
development. Visible/near infrared and chlorophyll fluorescence hyperspectral
images detected changes before symptom appearance at low-density inoculation. The
results of this study indicate that the P. cichorii infection severity can be
detected by chlorophyll fluorescence assay and hyperspectral images prior to the
onset of visible symptoms, indicating the feasibility of early detection of
diseases. However, to detect disease development by hyperspectral imaging, more
detailed protocols and analyses are necessary. Taken together, change in
chlorophyll fluorescence is a good parameter for early detection of P. cichorii
infection in tomato plants. In addition, image-based visualization of infection
severity before visual damage appearance will contribute to effective management
of plant diseases.
PMID- 27493606
TI - Defense-Related Responses in Fruit of the Nonhost Chili Pepper against
Xanthomonas axonopodis pv. glycines Infection.
AB - Xanthomonas axonopodis pv. glycines (Xag ) is a necrotrophic bacterial pathogen
of the soybean that causes bacterial pustules and is a nonhost pathogen of the
chili pepper. In the current study, chili pepper fruit wound inoculated in planta
with Xag 8ra formed necrotic lesions on the fruit surface and induced several
structural and chemical barriers systemically in the fruit tissue. The initial
defense response included programmed cell death of necrotizing and necrotized
cells, which was characterized by nuclear DNA cleavage, as detected by TUNEL
confocal laser scanning microscopy (CLSM), and phosphatidylserine exposure on
cell walls distal to the infection site, as detected by Annexin V FLUOS-CLSM.
These two responses may facilitate cell killing and enhance transportation of
cell wall materials used for cell wall thickening, respectively. The cells
beneath the necrotic tissue were enlarged and divided to form periclinal cell
walls, resulting in extensive formation of several parallel boundary layers at
the later stages of infection, accompanying the deposition of wall fortification
materials for strengthening structural defenses. These results suggest that
nonhost resistance of chili pepper fruit against the nonhost necrotrophic
pathogen Xag 8ra is activated systematically from the initial infection until
termination of the infection cycle, resulting in complete inhibition of bacterial
pathogenesis by utilizing organ-specific in situ physiological events governed by
the expression of genes in the plant fruit organ.
PMID- 27493607
TI - The Effects of High Temperature on Infection by Potato virus Y, Potato virus A,
and Potato leafroll virus.
AB - We examined the effects of temperature on acquisition of Potato virus Y-O (PVY
O), Potato virus A (PVA), and Potato leafroll virus (PLRV) by Myzus persicae by
performing transmission tests with aphids that acquired each virus at different
temperatures. Infection by PVY-O/PVA and PLRV increased with increasing plant
temperature in Nicotiana benthamiana and Physalis floridana, respectively, after
being transmitted by aphids that acquired them within a temperature range of 10
20 degrees C. However, infection rates subsequently decreased. Direct qRT-PCR of
RNA extracted from a single aphid showed that PLRV infection increased in the 10
20 degrees C range, but this trend also declined shortly thereafter. We examined
the effect of temperature on establishment of virus infection. The greatest
number of plants became infected when N. benthamiana was held at 20 degrees C
after inoculation with PVY-O or PVA. The largest number of P. floridana plants
became infected with PLRV when the plants were maintained at 25 degrees C. PLRV
levels were highest in P. floridana kept at 20-25 degrees C. These results
indicate that the optimum temperatures for proliferation of PVY-O/PVA and PLRV
differed. Western blot analysis showed that accumulations of PVY-O and PVA coat
proteins (CPs) were lower at 10 degrees C or 15 degrees C than at 20 degrees C
during early infection. However, accumulation increased over time. At 25 degrees
C or 30 degrees C, the CPs of both viruses accumulated during early infection but
disappeared as time passed. Our results suggest that symptom attenuation and
reduction of PVY-O and PVA CP accumulation at higher temperatures appear to be
attributable to increased RNA silencing.
PMID- 27493608
TI - Short-Term Effects of Low-Level Heavy Metal Contamination on Soil Health Analyzed
by Nematode Community Structure.
AB - The short-term effects of low-level contamination by heavy metals (As, Cd, Cu,
and Pb) on the soil health were examined by analyzing soil nematode community in
soils planted with tomatoes. For this, the soils were irrigated with five metal
concentrations ([1, 1/4, 1/4(2), 1/4(3), and 0] * maximum concentrations [MC]
detected in irrigation waters near abandoned mine sites) for 18 weeks. Heavy
metal concentrations were significantly increased in soils irrigated with MC of
heavy metals, among which As and Cu exceeded the maximum heavy metal residue
contents of soil approved in Korea. In no heavy metal treatment controls,
nematode abundances for all trophic groups (except omnivorous-predatory nematodes
[OP]) and colonizer-persister (cp) values (except cp-4-5) were significantly
increased, and all maturity indices (except maturity index [MI] of plant
parasitic nematodes) and structure index (SI) were significantly decreased,
suggesting the soil environments might have been disturbed during 18 weeks of
tomato growth. There were no concentration-dependent significant decreases in
richness, abundance, or MI for most heavy metals; however, their significant
decreases occurred in abundance and richness of OP and cp-4, MI2-5 (excluding cp
1) and SI, indicating disturbed soil ecosystems, at the higher concentrations (MC
and MC/4) of Pb that had the most significant negative correlation coefficients
for heavy metal concentrations and nematode community among the heavy metals.
Therefore, the short-term effects of low-level heavy metal contamination on soil
health can be analyzed by nematode community structures before the appearance of
plant damages caused by the abiotic agents, heavy metals.
PMID- 27493609
TI - Migration and Attacking Ability of Bursaphelenchus mucronatus in Pinus thunbergii
Stem Cuttings.
AB - To understand how Bursaphelenchus xylophilus kills pine trees, the differences
between the effects of B. xylophilus and B. mucronatus on pine trees are usually
compared. In this study, the migration and attacking ability of a non-pathogenic
B. mucronatus in Pinus thunbergii were investigated. The distribution of B.
mucronatus and the number of dead epithelial cells resulting from inoculation
were compared with those of the pathogenic B. xylophilus. Although B. mucronatus
is non-pathogenic in pines, its distribution pattern in P. thunbergii was the
same as that of B. xylophilus. We therefore concluded that the non-pathogenicity
of B. mucronatus could not be attributed to its migration ability. The sparse and
sporadic attacking pattern of B. mucronatus was also the same as that of B.
xylophilus. However, the number and area of the dead epithelial cells in pine
cuttings inoculated with B. mucronatus were smaller than in those cuttings
inoculated with B. xylophilus, meaning that the attacking ability of B.
mucronatus is weaker than that of B. xylophilus. Therefore, we concluded that the
weaker attacking ability of B. mucronatus might be the factor responsible for the
non-pathogenicity.
PMID- 27493610
TI - Identification and Expression Profiles of Six Transcripts Encoding
Carboxylesterase Protein in Vitis flexuosa Infected with Pathogens.
AB - Plants protect themselves from pathogen attacks via several mechanisms, including
hypersensitive cell death. Recognition of pathogen attack by the plant resistance
gene triggers expression of carboxylesterase genes associated with hypersensitive
response. We identified six transcripts of carboxylesterase genes, Vitis flexuosa
carboxylesterase 5585 (VfCXE5585), VfCXE12827, VfCXE13132, VfCXE17159,
VfCXE18231, and VfCXE47674, which showed different expression patterns upon
transcriptome analysis of V. flexuosa inoculated with Elsinoe ampelina. The
lengths of genes ranged from 1,098 to 1,629 bp, and their encoded proteins
consisted of 309 to 335 amino acids. The predicted amino acid sequences showed
hydrolase like domains in all six transcripts and contained two conserved motifs,
GXSXG of serine hydrolase characteristics and HGGGF related to the
carboxylesterase family. The deduced amino acid sequence also contained a
potential catalytic triad consisted of serine, aspartic acid and histidine. Of
the six transcripts, VfCXE12827 showed upregulated expression against E. ampelina
at all time points. Three genes (VfCXE5585, VfCXE12827, and VfCXE13132) showed
upregulation, while others (VfCXE17159, VfCXE18231, and VfCXE47674) were down
regulated in grapevines infected with Botrytis cinerea. All transcripts showed
upregulated expression against Rhizobium vitis at early and later time points
except VfCXE12827, and were downregulated for up to 48 hours post inoculation
(hpi) after upregulation at 1 hpi in response to R. vitis infection. All tested
genes showed high and differential expression in response to pathogens,
indicating that they all may play a role in defense pathways during pathogen
infection in grapevines.
PMID- 27493612
TI - Antibacterial Activity of Cinnamaldehyde and Estragole Extracted from Plant
Essential Oils against Pseudomonas syringae pv. actinidiae Causing Bacterial
Canker Disease in Kiwifruit.
AB - Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker disease in
kiwifruit. Antibacterial activity of plant essential oils (PEOs) originating from
49 plant species were tested against Psa by a vapor diffusion and a liquid
culture assays. The five PEOs from Pimenta racemosa, P. dioica, Melaleuca
linariifolia, M. cajuputii, and Cinnamomum cassia efficiently inhibited Psa
growth by either assays. Among their major components, estragole, eugenol, and
methyl eugenol showed significant antibacterial activity by only the liquid
culture assay, while cinnamaldehyde exhibited antibacterial activity by both
assays. The minimum inhibitory concentrations (MICs) of estragole and
cinnamaldehyde by the liquid culture assay were 1,250 and 2,500 ppm,
respectively. The MIC of cinnamaldehyde by the vapor diffusion assay was 5,000
ppm. Based on the formation of clear zones or the decrease of optical density
caused by these compounds, they might kill the bacterial cells and this feature
might be useful for managing the bacterial canker disease in kiwifruit.
PMID- 27493611
TI - A Rice Gene Homologous to Arabidopsis AGD2-LIKE DEFENSE1 Participates in Disease
Resistance Response against Infection with Magnaporthe oryzae.
AB - ALD1 (ABERRANT GROWTH AND DEATH2 [AGD2]-LIKE DEFENSE1) is one of the key defense
regulators in Arabidopsis thaliana and Nicotiana benthamiana. In these model
plants, ALD1 is responsible for triggering basal defense response and systemic
resistance against bacterial infection. As well ALD1 is involved in the
production of pipecolic acid and an unidentified compound(s) for systemic
resistance and priming syndrome, respectively. These previous studies proposed
that ALD1 is a potential candidate for developing genetically modified (GM)
plants that may be resistant to pathogen infection. Here we introduce a role of
ALD1-LIKE gene of Oryza sativa, named as OsALD1, during plant immunity. OsALD1
mRNA was strongly transcribed in the infected leaves of rice plants by
Magnaporthe oryzae, the rice blast fungus. OsALD1 proteins predominantly
localized at the chloroplast in the plant cells. GM rice plants over-expressing
OsALD1 were resistant to the fungal infection. The stable expression of OsALD1
also triggered strong mRNA expression of PATHOGENESIS-RELATED PROTEIN1 genes in
the leaves of rice plants during infection. Taken together, we conclude that
OsALD1 plays a role in disease resistance response of rice against the infection
with rice blast fungus.
PMID- 27493613
TI - Development of Virus-Induced Gene Expression and Silencing Vector Derived from
Grapevine Algerian Latent Virus.
AB - Grapevine Algerian latent virus (GALV) is a member of the genus Tombusvirus in
the Tombusviridae and infects not only woody perennial grapevine plant but also
herbaceous Nicotiana benthamiana plant. In this study, we developed GALV-based
gene expression and virus-induced gene silencing (VIGS) vectors in N.
benthamiana. The GALV coat protein deletion vector, pGMG, was applied to express
the reporter gene, green fluorescence protein (GFP), but the expression of GFP
was not detected due to the necrotic cell death on the infiltrated leaves. The
p19 silencing suppressor of GALV was engineered to inactivate its expression and
GFP was successfully expressed with unrelated silencing suppressor, HC-Pro, from
soybean mosaic virus. The pGMG vector was used to knock down magnesium chelatase
(ChlH) gene in N. benthamaina and the silencing phenotype was clearly observed on
systemic leaves. Altogether, the GALV-derived vector is expected to be an
attractive tool for useful gene expression and VIGS vectors in grapevine as well
as N. benthamiana.
PMID- 27493614
TI - The Role of CDK 4/6 Inhibitors in Breast Cancer Treatment.
PMID- 27493616
TI - Palbociclib: First CDK4/6 Inhibitor in Clinical Practice for the Treatment of
Advanced HR-Positive Breast Cancer.
AB - Palbociclib is the first inhibitor of the cyclin-dependent kinases (CDK) 4 and 6
to be introduced into clinical practice. Preclinical investigations led to its
clinical development in advanced hormone receptor (HR)-positive breast cancer. To
date, 2 significant clinical trials have been fully published. In this article,
the results of these trials and their clinical relevance for the management of HR
positive advanced breast cancer are discussed.
PMID- 27493615
TI - Clinical Development of the CDK4/6 Inhibitors Ribociclib and Abemaciclib in
Breast Cancer.
AB - Clinical and preclinical data support a significant role for inhibitors of the
cyclin-dependent kinases (CDKs) 4 and 6 in the treatment of patients with breast
cancer. Recently, based on data showing improvement in progression-free survival,
the use of palbociclib (Ibrance; Pfizer, Inc.) in combination with endocrine
agents was approved to treat patients with hormone receptor-positive advanced
disease. Importantly, 2 other CDK4/6 inhibitors, abemaciclib (LY2835219; Lilly)
and ribociclib (LEE011; Novartis), are in the late stage of clinical development.
In this review, we will focus on clinical data on these 2 new drugs, highlighting
their differences compared to palbociclib in terms of single-agent activity,
central nervous system penetration, and common adverse events. In addition, we
will present the ongoing clinical trials and discuss future directions in the
field.
PMID- 27493617
TI - Palbociclib - from Bench to Bedside and Beyond.
AB - Endocrine therapy is the cornerstone in the treatment of hormone receptor
positive breast cancer. During the last decades, much has been learned about the
subtle regulation of the cell cycle. In this tightly regulated network, cyclin
dependent kinases (CDKs) play a pivotal role. Especially CDK4/6 is the key
regulator of the G1-S transition. Realizing its importance, specific inhibitors
of CDK4/6 were developed. The drug most advanced in clinical development in this
class is palbociclib (PD 0332991). This review highlights preclinical data and
brings into focus early clinical trials that led to an accelerated approval by
the US Food and Drug Administration (FDA) as first-line treatment in combination
with letrozole in advanced hormone receptor-positive and human epidermal growth
factor receptor 2 (HER2)-negative breast cancer. Furthermore, ongoing clinical
trials with palbociclib in advanced and in early breast cancer are outlined. In
conclusion, inhibition of CDK4/6 using palbociclib in combination with endocrine
therapy is an efficacious treatment option in hormone receptor-positive/HER2
negative advanced breast cancer. Ongoing clinical trials will show whether
palbociclib is ready for prime time in early breast cancer.
PMID- 27493618
TI - Implementation of the German Mammography Screening Program (German MSP) and First
Results for Initial Examinations, 2005-2009.
AB - BACKGROUND: The German Mammography Screening Program (German MSP) is population
based and intended for women aged 50-69 years (approximately 10.5 million). The
program started in 2005 and was implemented within 5 years. This article
describes the implementation, structure, and screening process, and presents the
results of initial examinations for the prevalence phase. METHODS: Data were
collected annually from invitation centers (invitation, attendance), screening
units (performance, outcomes), and cancer registries (incidence). RESULTS: In
2009, 92% of all annually eligible women were invited; 50% of the annually
eligible population participated. The total cancer detection rate in the period
of 2005-2009 was 8.1/1,000; the corresponding recall rate was 5.9%. 19.6% of
detected cancers were ductal carcinoma in situ; 76.7% of invasive cancers were <=
20 mm in size, 30.2% were <= 10 mm, and 75.3% were node-negative. During the
implementation period, incidence increased by 37 and 56% in the old and new
federal states, respectively. Incidence rates decreased following the prevalence
phase. CONCLUSION: The German MSP was successfully implemented. The results of
the prevalence phase meet the target values of the European guidelines. Proper
functioning of the program is also verified by its effects on breast cancer
incidence. To draw reliable conclusions regarding the long-term effects of the
program, results from the routine screening rounds have to be awaited.
PMID- 27493619
TI - Factors Effecting Mastalgia.
AB - BACKGROUND: Breast pain is one of the leading complaints that ends up with
referral to breast surgery clinics. The purpose of the present study was to
investigate the factors that cause mastalgia, and its relation with benign or
malignant breast disease. METHODS: The study was performed in 700 patients. Data
obtained from surveys, and imaging findings were prospectively recorded, and
analyzed. RESULTS: The mean age was 45.20 +/- 10.78 years. The mastalgia group
included 500 cases; the asymptomatic group comprised 200 individuals. Stressful
lifestyle, caffeine consumption, and smoking were associated with mastalgia (p <
0.05). Rates of women who had breast fed 3 times or more were higher in the
mastalgia group (p < 0.05). Increased breast density, and breast imaging
reporting and data system (BI-RADS) 2 mammography findings were related with
mastalgia (p < 0.05). Cysts and fibroadenomas were more common in the mastalgia
group (p < 0.05). The incidence of a past history of malignant breast disease was
significantly higher in the mastalgia group (p < 0.05). CONCLUSIONS: Stress,
caffeine, smoking, lactation frequency, and benign disorders were factors
detected to be related with mastalgia. Although a significant relation between
mastalgia and malignant breast disease was detected in our study, more controlled
studies are still required to investigate this issue further.
PMID- 27493620
TI - Real-Time qPCR-Based Detection of Circulating Tumor Cells from Blood Samples of
Adjuvant Breast Cancer Patients: A Preliminary Study.
AB - BACKGROUND: Circulating tumor cells (CTCs) are cells that detach from a primary
tumor, circulate through the blood stream and lymphatic vessels, and are
considered to be the main reason for remote metastasis. Due to their origin,
tumor cells have different gene expression levels than the surrounding blood
cells. Therefore, they might be detectable in blood samples from breast cancer
patients by real-time quantitative polymerase chain reaction (RT-qPCR). MATERIALS
AND METHODS: Blood samples of healthy donors and adjuvant breast cancer patients
were withdrawn and the cell fraction containing white blood cells and tumor cells
was enriched by density gradient centrifugation. RNA was isolated and reverse
transcribed to cDNA, which was then used in TaqMan real-time PCR against
cytokeratin (CK)8, CK18 and CK19. 18S and GAPDH were used as controls. RESULTS:
All 3 CKs were, on average, found to be significantly higher expressed in
adjuvant breast cancer samples compared to negative controls, probably due to the
presence of CTCs. Unfortunately, gene expression levels could not be correlated
to tumor characteristics. CONCLUSIONS: RT-qPCR could make up a new approach for
the detection of CTCs from blood samples of breast cancer patients, but a
correlation of the PCR data to gold standard methods in CTC detection would help
to further improve the informative value of the qPCR results.
PMID- 27493622
TI - AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast
Cancer: Update 2016.
PMID- 27493621
TI - Breast Tuberculosis after Chest Trauma - a Case Report and Review of the
Literature.
AB - BACKGROUND: Breast involvement of tuberculosis (TB) is well known but uncommon.
It can resemble other diseases, including breast cancer, and diagnosis is quite
difficult. So, when facing a breast lesion, a possible tubercular etiology should
always be born in mind, relying on qualified laboratories to confirm the
diagnosis. CASE REPORT: We describe a 42-year-old woman with a mammary fistula
complicating a post-traumatic lump. A critical analysis of the diagnostic process
was performed together with a review of the literature, also considering the
potential role of trauma in inducing such a rare complication.
PMID- 27493623
TI - AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and
Metastatic Breast Cancer: Update 2016.
PMID- 27493624
TI - Acceleration of Deep Neural Network Training with Resistive Cross-Point Devices:
Design Considerations.
AB - In recent years, deep neural networks (DNN) have demonstrated significant
business impact in large scale analysis and classification tasks such as speech
recognition, visual object detection, pattern extraction, etc. Training of large
DNNs, however, is universally considered as time consuming and computationally
intensive task that demands datacenter-scale computational resources recruited
for many days. Here we propose a concept of resistive processing unit (RPU)
devices that can potentially accelerate DNN training by orders of magnitude while
using much less power. The proposed RPU device can store and update the weight
values locally thus minimizing data movement during training and allowing to
fully exploit the locality and the parallelism of the training algorithm. We
evaluate the effect of various RPU device features/non-idealities and system
parameters on performance in order to derive the device and system level
specifications for implementation of an accelerator chip for DNN training in a
realistic CMOS-compatible technology. For large DNNs with about 1 billion weights
this massively parallel RPU architecture can achieve acceleration factors of 30,
000 * compared to state-of-the-art microprocessors while providing power
efficiency of 84, 000 GigaOps/s/W. Problems that currently require days of
training on a datacenter-size cluster with thousands of machines can be addressed
within hours on a single RPU accelerator. A system consisting of a cluster of RPU
accelerators will be able to tackle Big Data problems with trillions of
parameters that is impossible to address today like, for example, natural speech
recognition and translation between all world languages, real-time analytics on
large streams of business and scientific data, integration, and analysis of
multimodal sensory data flows from a massive number of IoT (Internet of Things)
sensors.
PMID- 27493627
TI - The Functional Networks of Prepulse Inhibition: Neuronal Connectivity Analysis
Based on FDG-PET in Awake and Unrestrained Rats.
AB - Prepulse inhibition (PPI) is a neuropsychological process during which a weak
sensory stimulus ("prepulse") attenuates the motor response ("startle reaction")
to a subsequent strong startling stimulus. It is measured as a surrogate marker
of sensorimotor gating in patients suffering from neuropsychological diseases
such as schizophrenia, as well as in corresponding animal models. A variety of
studies has shown that PPI of the acoustical startle reaction comprises three
brain circuitries for: (i) startle mediation, (ii) PPI mediation, and (iii)
modulation of PPI mediation. While anatomical connections and information flow in
the startle and PPI mediation pathways are well known, spatial and temporal
interactions of the numerous regions involved in PPI modulation are incompletely
understood. We therefore combined [(18)F]fluoro-2-deoxyglucose positron-emission
tomography (FDG-PET) with PPI and resting state control paradigms in awake rats.
A battery of subtractive, correlative as well as seed-based functional
connectivity analyses revealed a default mode-like network (DMN) active during
resting state only. Furthermore, two functional networks were observed during
PPI: Metabolic activity in the lateral circuitry was positively correlated with
PPI effectiveness and involved the auditory system and emotional regions. The
medial network was negatively correlated with PPI effectiveness, i.e., associated
with startle, and recruited a spatial/cognitive network. Our study provides
evidence for two distinct neuronal networks, whose continuous interplay
determines PPI effectiveness in rats, probably by either protecting the prepulse
or facilitating startle processing. Discovering similar networks affected in
neuropsychological disorders may help to better understand mechanisms of
sensorimotor gating deficits and provide new perspectives for therapeutic
strategies.
PMID- 27493626
TI - The Autophagoproteasome a Novel Cell Clearing Organelle in Baseline and
Stimulated Conditions.
AB - Protein clearing pathways named autophagy (ATG) and ubiquitin proteasome (UP)
control homeostasis within eukaryotic cells, while their dysfunction produces
neurodegeneration. These pathways are viewed as distinct biochemical cascades
occurring within specific cytosolic compartments owing pathway-specific enzymatic
activity. Recent data strongly challenged the concept of two morphologically
distinct and functionally segregated compartments. In fact, preliminary evidence
suggests the convergence of these pathways to form a novel organelle named
autophagoproteasome. This is characterized in the present study by using a cell
line where, mTOR activity is upregulated and autophagy is suppressed. This was
reversed dose-dependently by administering the mTOR inhibitor rapamycin. Thus, we
could study autophagoproteasomes when autophagy was either suppressed or
stimulated. The occurrence of autophagoproteasome was shown also in non-human
cell lines. Ultrastructural morphometry, based on the stochiometric binding of
immunogold particles allowed the quantitative evaluation of ATG and UP component
within autophagoproteasomes. The number of autophagoproteasomes increases
following mTOR inhibition. Similarly, mTOR inhibition produces overexpression of
both LC3 and P20S particles. This is confirmed by the fact that the ratio of free
vs. autophagosome-bound LC3 is similar to that measured for P20S, both in
baseline conditions and following mTOR inhibition. Remarkably, within
autophagoproteasomes there is a slight prevalence of ATG compared with UP
components for low rapamycin doses, whereas for higher rapamycin doses UP
increases more than ATG. While LC3 is widely present within cytosol, UP is
strongly polarized within autophagoproteasomes. These fine details were evident
at electron microscopy but could not be deciphered by using confocal microscopy.
Despite its morphological novelty autophagoproteasomes appear in the natural site
where clearing pathways (once believed to be anatomically segregated) co-exist
and they are likely to interact at molecular level. In fact, LC3 and P20S co
immunoprecipitate, suggesting a specific binding and functional interplay, which
may be altered by inhibiting mTOR. In summary, ATG and UP often represent two
facets of a single organelle, in which unexpected amount of enzymatic activity
should be available. Thus, autophagoproteasome may represent a sophisticated
ultimate clearing apparatus.
PMID- 27493625
TI - Functional Relevance of Different Basal Ganglia Pathways Investigated in a
Spiking Model with Reward Dependent Plasticity.
AB - The brain enables animals to behaviorally adapt in order to survive in a complex
and dynamic environment, but how reward-oriented behaviors are achieved and
computed by its underlying neural circuitry is an open question. To address this
concern, we have developed a spiking model of the basal ganglia (BG) that learns
to dis-inhibit the action leading to a reward despite ongoing changes in the
reward schedule. The architecture of the network features the two pathways
commonly described in BG, the direct (denoted D1) and the indirect (denoted D2)
pathway, as well as a loop involving striatum and the dopaminergic system. The
activity of these dopaminergic neurons conveys the reward prediction error (RPE),
which determines the magnitude of synaptic plasticity within the different
pathways. All plastic connections implement a versatile four-factor learning rule
derived from Bayesian inference that depends upon pre- and post-synaptic
activity, receptor type, and dopamine level. Synaptic weight updates occur in the
D1 or D2 pathways depending on the sign of the RPE, and an efference copy informs
upstream nuclei about the action selected. We demonstrate successful performance
of the system in a multiple-choice learning task with a transiently changing
reward schedule. We simulate lesioning of the various pathways and show that a
condition without the D2 pathway fares worse than one without D1. Additionally,
we simulate the degeneration observed in Parkinson's disease (PD) by decreasing
the number of dopaminergic neurons during learning. The results suggest that the
D1 pathway impairment in PD might have been overlooked. Furthermore, an analysis
of the alterations in the synaptic weights shows that using the absolute reward
value instead of the RPE leads to a larger change in D1.
PMID- 27493628
TI - Aesthetics by Numbers: Links between Perceived Texture Qualities and Computed
Visual Texture Properties.
AB - Our world is filled with texture. For the human visual system, this is an
important source of information for assessing environmental and material
properties. Indeed-and presumably for this reason-the human visual system has
regions dedicated to processing textures. Despite their abundance and apparent
relevance, only recently the relationships between texture features and high
level judgments have captured the interest of mainstream science, despite long
standing indications for such relationships. In this study, we explore such
relationships, as these might be used to predict perceived texture qualities.
This is relevant, not only from a psychological/neuroscience perspective, but
also for more applied fields such as design, architecture, and the visual arts.
In two separate experiments, observers judged various qualities of visual
textures such as beauty, roughness, naturalness, elegance, and complexity. Based
on factor analysis, we find that in both experiments, ~75% of the variability in
the judgments could be explained by a two-dimensional space, with axes that are
closely aligned to the beauty and roughness judgments. That a two-dimensional
judgment space suffices to capture most of the variability in the perceived
texture qualities suggests that observers use a relatively limited set of
internal scales on which to base various judgments, including aesthetic ones.
Finally, for both of these judgments, we determined the relationship with a large
number of texture features computed for each of the texture stimuli. We find that
the presence of lower spatial frequencies, oblique orientations, higher intensity
variation, higher saturation, and redness correlates with higher beauty ratings.
Features that captured image intensity and uniformity correlated with roughness
ratings. Therefore, a number of computational texture features are predictive of
these judgments. This suggests that perceived texture qualities-including the
aesthetic appreciation-are sufficiently universal to be predicted-with reasonable
accuracy-based on the computed feature content of the textures.
PMID- 27493629
TI - Pyrrolidine Dithiocarbamate Prevents Neuroinflammation and Cognitive Dysfunction
after Endotoxemia in Rats.
AB - Systemic inflammation, for example as a result of infection, often contributes to
long-term complications. Neuroinflammation and cognitive decline are key
hallmarks of several neurological conditions, including advance age. The
contribution of systemic inflammation to the central nervous system (CNS) remains
not fully understood. Using a model of peripheral endotoxemia with
lipopolysaccharide (LPS) we investigated the role of nuclear factor-kappaB (NF
kappaB) activity in mediating long-term neuroinflammation and cognitive
dysfunction in aged rats. Herein we describe the anti-inflammatory effects of
pyrrolidine dithiocarbamate (PDTC), a selective NF-kappaB inhibitor, in
modulating systemic cytokines including tumor necrosis factor (TNF)-alpha and
interleukin-1beta (IL-1beta) and CNS markers after LPS exposure in aged rats. In
the hippocampus, PDTC not only reduced neuroinflammation by modulating canonical
NF-kappaB activity but also affected IL-1beta expression in astrocytes. Parallel
effects were observed on behavior and postsynaptic density-95 (PSD95), a marker
of synaptic function. Taken together these changes improved acute and long-term
cognitive function in aged rats after LPS exposure.
PMID- 27493631
TI - Paeonol Protects Rat Heart by Improving Regional Blood Perfusion during No
Reflow.
AB - No-reflow phenomenon, defined as inadequate perfusion of myocardium without
evident artery obstruction, occurs at a high incidence after coronary
revascularization. The mechanisms underlying no-reflow is only partially
understood. It is commonly caused by the swelling of endothelial cells,
neutrophil accumulation, and vasoconstriction, which are all related to acute
inflammation. Persistent no-reflow can lead to hospitalization and mortality.
However, an effective preventive intervention has not yet been established. We
have previously found that paeonol, an active extraction from the root of Paeonia
suffruticosa, can benefit the heart function by inhibiting tissue damage after
ischemia, reducing inflammation, and inducing vasodilatation. To further
investigate the potential cardioprotective action of paeonol on no-reflow,
healthy male Wistar rats were randomly divided into four groups: sham, ischemia
reperfusion (I/R) injury (left anterior descending coronary artery was ligated
for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol
at two different doses. Real-time myocardial contrast echocardiography was used
to monitor regional blood perfusion and cardiac functions. Our data indicated
that paeonol treatment significantly reduces myocardial infarct area and no
reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A.beta) and cardiac
functions such as ejection fraction, stroke volume, and fractional shortening
were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels
of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive
protein, as indices of myocardial injury. Paeonol exerts beneficial effects on
attenuating I/R-associated no-reflow injuries, and may be considered as a
potential preventive treatment for cardiac diseases or post-coronary
revascularization in which no-reflow often occurs.
PMID- 27493632
TI - "Decoding" Angiogenesis: New Facets Controlling Endothelial Cell Behavior.
AB - Angiogenesis, the formation of new blood vessels, is a unique and crucial
biological process occurring during both development and adulthood. A better
understanding of the mechanisms that regulates such process is mandatory to
intervene in pathophysiological conditions. Here we highlight some recent
argument on new players that are critical in endothelial cells, by summarizing
novel discoveries that regulate notorious vascular pathways such as Vascular
Endothelial Growth Factor (VEGF), Notch and Planar Cell Polarity (PCP), and by
discussing more recent findings that put metabolism, redox signaling and
hemodynamic forces as novel unforeseen facets in angiogenesis. These new aspects,
that critically regulate angiogenesis and vascular homeostasis in health and
diseased, represent unforeseen new ground to develop anti-angiogenic therapies.
PMID- 27493630
TI - Animal-Free Chemical Safety Assessment.
AB - The exponential growth of the Internet of Things and the global popularity and
remarkable decline in cost of the mobile phone is driving the digital
transformation of medical practice. The rapidly maturing digital, non-medical
world of mobile (wireless) devices, cloud computing and social networking is
coalescing with the emerging digital medical world of omics data, biosensors and
advanced imaging which offers the increasingly realistic prospect of personalized
medicine. Described as a potential "seismic" shift from the current "healthcare"
model to a "wellness" paradigm that is predictive, preventative, personalized and
participatory, this change is based on the development of increasingly
sophisticated biosensors which can track and measure key biochemical variables in
people. Additional key drivers in this shift are metabolomic and proteomic
signatures, which are increasingly being reported as pre-symptomatic, diagnostic
and prognostic of toxicity and disease. These advancements also have profound
implications for toxicological evaluation and safety assessment of
pharmaceuticals and environmental chemicals. An approach based primarily on human
in vivo and high-throughput in vitro human cell-line data is a distinct
possibility. This would transform current chemical safety assessment practice
which operates in a human "data poor" to a human "data rich" environment. This
could also lead to a seismic shift from the current animal-based to an animal
free chemical safety assessment paradigm.
PMID- 27493634
TI - Bubbles Quantified In vivo by Ultrasound Relates to Amount of Gas Detected Post
mortem in Rabbits Decompressed from High Pressure.
AB - The pathophysiological mechanism of decompression sickness is not fully
understood but there is evidence that it can be caused by intravascular and
autochthonous bubbles. Doppler ultrasound at a given circulatory location is used
to detect and quantify the presence of intravascular gas bubbles as an indicator
of decompression stress. In this manuscript we studied the relationship between
presence and quantity of gas bubbles by echosonography of the pulmonary artery of
anesthetized, air-breathing New Zealand White rabbits that were compressed and
decompressed. Mortality rate, presence, quantity, and distribution of gas bubbles
elsewhere in the body was examined postmortem. We found a strong positive
relationship between high ultrasound bubble grades in the pulmonary artery,
sudden death, and high amount of intra and extra vascular gas bubbles widespread
throughout the entire organism. In contrast, animals with lower bubble grades
survived for 1 h after decompression until sacrificed, and showed no gas bubbles
during dissection.
PMID- 27493633
TI - What Is the Arrhythmic Substrate in Viral Myocarditis? Insights from Clinical and
Animal Studies.
AB - Sudden cardiac death (SCD) remains an unsolved problem in the twenty-first
century. It is often due to rapid onset, ventricular arrhythmias caused by a
number of different clinical conditions. A proportion of SCD patients have
identifiable diseases such as cardiomyopathies, but for others, the causes are
unknown. Viral myocarditis is becoming increasingly recognized as a contributor
to unexplained mortality, and is thought to be a major cause of SCD in the first
two decades of life. Myocardial inflammation, ion channel dysfunction,
electrophysiological, and structural remodeling may play important roles in
generating life-threatening arrhythmias. The aim of this review article is to
examine the electrophysiology of action potential conduction and repolarization
and the mechanisms by which their derangements lead to triggered and reentrant
arrhythmogenesis. By synthesizing experimental evidence from pre-clinical and
clinical studies, a framework of how host (inflammation), and viral (altered
cellular signaling) factors can induce ion electrophysiological and structural
remodeling is illustrated. Current pharmacological options are mainly supportive,
which may be accompanied by mechanical circulatory support. Heart transplantation
is the only curative option in the worst case scenario. Future strategies for the
management of viral myocarditis are discussed.
PMID- 27493635
TI - The Phantom Vanish Magic Trick: Investigating the Disappearance of a Non-existent
Object in a Dynamic Scene.
AB - Drawing inspiration from sleight-of-hand magic tricks, we developed an
experimental paradigm to investigate whether magicians' misdirection techniques
could be used to induce the misperception of "phantom" objects. While previous
experiments investigating sleight-of-hand magic tricks have focused on creating
false assumptions about the movement of an object in a scene, our experiment
investigated creating false assumptions about the presence of an object in a
scene. Participants watched a sequence of silent videos depicting a magician
performing with a single object. Following each video, participants were asked to
write a description of the events in the video. In the final video, participants
watched the Phantom Vanish Magic Trick, a novel magic trick developed for this
experiment, in which the magician pantomimed the actions of presenting an object
and then making it magically disappear. No object was presented during the final
video. The silent videos precluded the use of false verbal suggestions, and
participants were not asked leading questions about the objects. Nevertheless,
32% of participants reported having visual impressions of non-existent objects.
These findings support an inferential model of perception, wherein top-down
expectations can be manipulated by the magician to generate vivid illusory
experiences, even in the absence of corresponding bottom-up information.
PMID- 27493636
TI - Editorial: Mathematical and Statistics Anxiety: Educational, Social,
Developmental and Cognitive Perspectives.
PMID- 27493637
TI - Does Exercise Improve Cognitive Performance? A Conservative Message from Lord's
Paradox.
AB - Although extant meta-analyses support the notion that exercise results in
cognitive performance enhancement, methodology shortcomings are noted among
primary evidence. The present study examined relevant randomized controlled
trials (RCTs) published in the past 20 years (1996-2015) for methodological
concerns arise from Lord's paradox. Our analysis revealed that RCTs supporting
the positive effect of exercise on cognition are likely to include Type I
Error(s). This result can be attributed to the use of gain score analysis on
pretest-posttest data as well as the presence of control group superiority over
the exercise group on baseline cognitive measures. To improve accuracy of causal
inferences in this area, analysis of covariance on pretest-posttest data is
recommended under the assumption of group equivalence. Important experimental
procedures are discussed to maintain group equivalence.
PMID- 27493638
TI - Better Working Memory and Motor Inhibition in Children Who Delayed Gratification.
AB - BACKGROUND: Despite the extensive research on delayed gratification over the past
few decades, the neurocognitive processes that subserve delayed gratification
remains unclear. As an exploratory step in studying these processes, the present
study aims to describe the executive function profiles of children who were
successful at delaying gratification and those who were not. METHODS: A total of
138 kindergarten students (65 males, 73 females; M age = 44 months, SD = 3.5; age
range = 37-53 months) were administered a delayed gratification task, a 1-back
test, a Day/night Stroop test and a Go/no-go test. The outcome measures of these
tests were then analyzed between groups using a Multivariate Analysis of
Variance, and subsequently a Multivariate Analysis of Covariance incorporating
age as a covariate. RESULTS: Children who were successful in delaying
gratification were significantly older and had significantly better outcomes in
the 1-back test and go/no-go test. With the exception of the number of hits in
the go/no-go test, all other group differences remained significant after
controlling for age. CONCLUSION: Children who were successful in delaying
gratification showed better working memory and motor inhibition relative to those
who failed the delayed gratification task. The implications of these findings are
discussed.
PMID- 27493639
TI - How Parents Read Counting Books and Non-numerical Books to Their Preverbal
Infants: An Observational Study.
AB - Studies have stressed the importance of counting with children to promote formal
numeracy abilities; however, little work has investigated when parents begin to
engage in this behavior with their young children. In the current study, we
investigated whether parents elaborated on numerical information when reading a
counting book to their preverbal infants and whether developmental differences in
numerical input exist even in the 1st year of life. Parents and their 5-10 months
old infants were asked to read, as they would at home, two books to their
infants: a counting book and another book that did not have numerical content.
Parents' spontaneous statements rarely focused on number and those that did
consisted primarily of counting, with little emphasis on labeling the cardinality
of the set. However, developmental differences were observed even in this age
range, such that parents were more likely to make numerical utterances when
reading to older infants. Together, results are the first to characterize
naturalistic reading behaviors between parents and their preverbal infants in the
context of counting books, suggesting that although counting books promote
numerical language in parents, infants still receive very little in the way of
numerical input before the end of the 1st year of life. While little is known
regarding the impact of number talk on the cognitive development of young
infants, the current results may guide future work in this area by providing the
first assessment of the characteristics of parental numerical input to preverbal
infants.
PMID- 27493640
TI - Erratum: 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.
AB - [This corrects the article on p. 28 in vol. 7, PMID: 26858675.].
PMID- 27493641
TI - The Exposed Proteomes of Brachyspira hyodysenteriae and B. pilosicoli.
AB - Brachyspira hyodysenteriae and Brachyspira pilosicoli are well-known intestinal
pathogens in pigs. B. hyodysenteriae is the causative agent of swine dysentery, a
disease with an important impact on pig production while B. pilosicoli is
responsible of a milder diarrheal disease in these animals, porcine intestinal
spirochetosis. Recent sequencing projects have provided information for the
genome of these species facilitating the search of vaccine candidates using
reverse vaccinology approaches. However, practically no experimental evidence
exists of the actual gene products being expressed and of those proteins exposed
on the cell surface or released to the cell media. Using a cell-shaving strategy
and a shotgun proteomic approach we carried out a large-scale characterization of
the exposed proteins on the bacterial surface in these species as well as of
peptides and proteins in the extracellular medium. The study included three
strains of B. hyodysenteriae and two strains of B. pilosicoli and involved 148 LC
MS/MS runs on a high resolution Orbitrap instrument. Overall, we provided
evidence for more than 29,000 different peptides pointing to 1625 and 1338
different proteins in B. hyodysenteriae and B. pilosicoli, respectively. Many of
the most abundant proteins detected corresponded to described virulence factors
and vaccine candidates. The level of expression of these proteins, however, was
different among species and strains, stressing the value of determining actual
gene product levels as a complement of genomic-based approaches for vaccine
design.
PMID- 27493642
TI - Detection of Cronobacter Genus in Powdered Infant Formula by Enzyme-linked
Immunosorbent Assay Using Anti-Cronobacter Antibody.
AB - Cronobacter species (Cronobacter spp.) are hazardous foodborne pathogens
associated with baby food, powdered infant formula (PIF). To develop a rapid and
sensitive method for simultaneous detection of seven Cronobacter spp. in PIF, an
indirect non-competitive enzyme-linked immunosorbent assay (INC-ELISA) was
developed based on a novel immunoglobulin G (IgG), anti-Cronobacter IgG. The
developed INC-ELISA was able to detect seven Cronobacter spp. at concentrations
ranging from (5.6 +/- 0.30) * 10(3) to (2.1 +/- 0.01) * 10(5) colony forming unit
(CFU)/mL in pure culture. Further, INC-ELISA employing anti-Cronobacter IgG was
applicable for analysis of PIF samples contaminated with less than <10 cells of
Cronobacter spp. per 25 g of PIF in 36 h. The developed antibody showed slight
cross-reactivity with Franconibacter pulveris (LMG 24057) at high concentration
(10(8) CFU/mL). The INC-ELISA method displayed excellent specificity without
compromising cross-reactivity with other foodborne pathogens. The INC-ELISA assay
method developed in this study using a novel anti-Cronobacter IgG facilitated
highly sensitive, efficient, and rapid detection of Cronobacter spp. in baby
food.
PMID- 27493643
TI - Phylogenomic Analyses and Reclassification of Species within the Genus
Tsukamurella: Insights to Species Definition in the Post-genomic Era.
AB - Owing to the highly similar phenotypic profiles, protein spectra and 16S rRNA
gene sequences observed between three pairs of Tsukamurella species (Tsukamurella
pulmonis/Tsukamurella spongiae, Tsukamurella tyrosinosolvens/Tsukamurella carboxy
divorans, and Tsukamurella pseudospumae/Tsukamurella sunchonensis), we
hypothesize that and the six Tsukamurella species may have been misclassified and
that there may only be three Tsukamurella species. In this study, we
characterized the type strains of these six Tsukamurella species by tradition DNA
DNA hybridization (DDH) and "digital DDH" after genome sequencing to determine
their exact taxonomic positions. Traditional DDH showed 81.2 +/- 0.6% to 99.7 +/-
1.0% DNA-DNA relatedness between the two Tsukamurella species in each of the
three pairs, which was above the threshold for same species designation. "Digital
DDH" based on Genome-To-Genome Distance Calculator and Average Nucleotide
Identity for the three pairs also showed similarity results in the range of 82.3
92.9 and 98.1-99.1%, respectively, in line with results of traditional DDH. Based
on these evidence and according to Rules 23a and 42 of the Bacteriological Code,
we propose that T. spongiae Olson et al. 2007, should be reclassified as a later
heterotypic synonym of T. pulmonis Yassin et al. 1996, T. carboxydivorans Park et
al. 2009, as a later heterotypic synonym of T. tyrosinosolvens Yassin et al.
1997, and T. sunchonensis Seong et al. 2008 as a later heterotypic synonym of T.
pseudospumae Nam et al. 2004. With the advancement of genome sequencing
technologies, classification of bacterial species can be readily achieved by
"digital DDH" than traditional DDH.
PMID- 27493645
TI - Transcriptomic Analysis of Staphylococcus epidermidis Biofilm-Released Cells upon
Interaction with Human Blood Circulating Immune Cells and Soluble Factors.
PMID- 27493644
TI - The New Antimicrobial Peptide SpHyastatin from the Mud Crab Scylla paramamosain
with Multiple Antimicrobial Mechanisms and High Effect on Bacterial Infection.
AB - SpHyastatin was first identified as a new cationic antimicrobial peptide in
hemocytes of the mud crab Scylla paramamosain. Based on the amino acid sequences
deduced, it was predicted that this peptide was composed of two different
functional domains, a proline-rich domain (PRD) and a cysteine-rich domain (CRD).
The recombinant product of SpHyastatin displayed potent antimicrobial activities
against the human pathogen Staphylococcus aureus and the aquatic animal pathogens
Aeromonas hydrophila and Pseudomonas fluorescens. Compared with the CRD of
SpHyastatin, the PRD presented better antimicrobial and chitin binding
activities, but both regions were essential for allowing SpHyastatin complete
antimicrobial activity. The binding properties of SpHyastatin to different
microbial surface molecules suggested that this might be an initial and crucial
step for performing its antimicrobial activities. Evaluated using propidium
iodide uptake assays and scanning electron microscopy images, the antimicrobial
mechanism of SpHyastatin was found to be prone to disrupt cell membrane
integrity. Interestingly, SpHyastatin exerted its role specifically on the
surface of S. aureus and Pichia pastoris whereas it directly killed P.
fluorescens through simultaneous targeting the membrane and the cytoplasm,
indicating that SpHyastatin could use different antimicrobial mechanisms to kill
different species of microbes. As expected, the recombinant SpHyastatin increased
the survival rate of crabs challenged with Vibrio parahaemolyticus. In addition,
SpHyastatin could modulate some V. parahaemolyticus-responsive genes in S.
paramamosain.
PMID- 27493646
TI - Analysis of the Changes in Expression Levels of Sialic Acid on Influenza-Virus
Infected Cells Using Lectin-Tagged Polymeric Nanoparticles.
AB - Viral infections affect millions around the world, sometimes leading to severe
consequences or even epidemics. Understanding the molecular dynamics during viral
infections would provide crucial information for preventing or stopping the
progress of infections. However, the current methods often involve the disruption
of the infected cells or expensive and time-consuming procedures. In this study,
fluorescent polymeric nanoparticles were fabricated and used as bioimaging
nanoprobes that can monitor the progression of influenza viral infection through
the changes in the expression levels of sialic acids expressed on the cell
membrane. The nanoparticles were composed of a biocompatible monomer to prevent
non-specific interactions, a hydrophobic monomer to form the core, a fluorescent
monomer, and a protein-binding monomer to conjugate lectin, which binds sialic
acids. It was shown that these lectin-tagged nanoparticles that specifically
target sialic acids could track the changes in the expression levels of sialic
acids caused by influenza viral infections in human lung epithelial cells. There
was a sudden drop in the levels of sialic acid at the initial onset of virus
infection (t = 0~1 h) and at approximately 4~5 h post-infection. The latter drop
correlated with the production of viral proteins that was confirmed using
traditional techniques. Thus, the accuracy, the rapidity and the efficacy of the
nanoprobes were demonstrated. Such molecular bioimaging tools, which allow easy
handling and in situ monitoring, would be useful to directly observe and decipher
the viral infection mechanisms.
PMID- 27493647
TI - Molecular Underpinnings of Nitrite Effect on CymA-Dependent Respiration in
Shewanella oneidensis.
AB - Shewanella exhibit a remarkable versatility of respiration, with a diverse array
of electron acceptors (EAs). In environments where these bacteria thrive,
multiple EAs are usually present. However, we know little about strategies by
which these EAs and their interaction affect ecophysiology of Shewanella. In this
study, we demonstrate in the model strain, Shewanella oneidensis MR-1, that
nitrite, not through nitric oxide to which it may convert, inhibits respiration
of fumarate, and probably many other EAs whose reduction depends on quinol
dehydrogenase CymA. This is achieved via the repression of cyclic adenosine
monophosphate (cAMP) production, a second messenger required for activation of
cAMP-receptor protein (Crp) which plays a primary role in regulation of
respiration. If nitrite is not promptly removed, intracellular cAMP levels drop,
and this impairs Crp activity. As a result, the production of nitrite reductase
NrfA, CymA, and fumarate reductase FccA is substantially reduced. In contrast,
nitrite can be simultaneously respired with trimethylamine N-oxide, resulting in
enhanced biomass.
PMID- 27493648
TI - Global Methylation Patterns and Their Relationship with Gene Expression and Small
RNA in Rice Lines with Different Ploidy.
AB - Whole genome duplication (WGD) is a major force in angiosperm evolution. Whether
WGD is accompanied by the evolution of epigenetic regulators remains to be
explored. Here we investigate whole genome methylation, gene expression, and
miRNA regulation among monoploid, diploid, and triploid rice plants isolated from
a twin-seedling population. The DNA methylation patterns in the three different
ploidy plants were highly similar, with DNA methylation primarily enriched in the
promoters. We examined the methylation of single genes and detected around 25,500
methylated genes, of which 22,751 were methylated in all three lines.
Significantly divergent DNA methylation patterns between each pair of three lines
were only detected in 64 genes, though more genes were found to exhibit
differential expression. Analysis of DNA methylation and expression patterns
showed that higher DNA methylation levels upstream of the transcription start
sites are correlated with higher levels of expression of related genes; whereas
higher DNA methylation levels in gene body regions are correlated with lower
levels of expression. We also carried out high-throughput sequencing of small RNA
libraries and identified 36 new miRNAs. These miRNAs have different expression
levels depending on the ploidy.
PMID- 27493649
TI - Nitrogen Mineralization of a Loam Soil Supplemented with Organic-Inorganic
Amendments under Laboratory Incubation.
AB - The quantification of nitrogen (N) supplying capacity of organic amendments
applied to a soil is of immense importance to examine synchronization, N release
capacity, and fertilizer values of these added materials. The aims of the present
study was to determine the potential N mineralization and subsequent
nitrification of separate and combined use of poultry manure (PM), wheat straw
residues (WSR), and urea N (UN) applied to a loam soil incubated periodically
over 140 days period. In addition, changes in total soil N and carbon contents
were also monitored during the study. Treatments included: PM100, WSR100, PM50 +
WSR50, UN100, UN50 + PM50, UN50 + WSR50, UN50 + PM25 + WSR25, and a control
(unfertilized). All the amendments were applied on an N-equivalent basis at the
rate of 200 mg N kg(-1). Results indicated that a substantial quantity of N had
been released from the added amendments into the soil mineral pool and the net
cumulative N mineralized varied between 39 and 147 mg N kg(-1), lowest in the WSR
and highest in the UN50 + PM50. Significant differences were observed among the
amendments and the net mineral N derived from a separate and combined use of PM
was greater than the other treatments. The net cumulative N nitrified (NCNN)
varied between 16 and 126 mg kg(-1), highest in UN50 + PM50 treatment. On
average, percentage conversion of added N into available N by different
amendments varied between 21 and 80%, while conversion of applied N into NO3 (-)
N ranged between 9 and 65%, and the treatment UN50 + PM50 displayed the highest N
recovery. Urea N when applied alone showed disappearance of 37% N (N unaccounted
for) at the end while application of PM and WSR with UN reduced N disappearance
and increased N retention in the mineral pool for a longer period. Organic
amendments alone or in combination with UN improved organic matter buildup and
increased soil N concentration. These results demonstrate the existence of
substantial amounts of N reserves present in PM and WSR that can be utilized
efficiently and effectively as potential N source for the management of nutrient
poor soils and plant growth.
PMID- 27493650
TI - Geminivirus-Mediated Genome Editing in Potato (Solanum tuberosum L.) Using
Sequence-Specific Nucleases.
AB - Genome editing using sequence-specific nucleases (SSNs) is rapidly being
developed for genetic engineering in crop species. The utilization of zinc finger
nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and
clustered regularly interspaced short palindromic repeats/CRISPR-associated
systems (CRISPR/Cas) for inducing double-strand breaks facilitates targeting of
virtually any sequence for modification. Targeted mutagenesis via non-homologous
end-joining (NHEJ) has been demonstrated extensively as being the preferred DNA
repair pathway in plants. However, gene targeting via homologous recombination
(HR) remains more elusive but could be a powerful tool for directed DNA repair.
To overcome barriers associated with gene targeting, a geminivirus replicon (GVR)
was used to deliver SSNs targeting the potato ACETOLACTATE SYNTHASE1 (ALS1) gene
and repair templates designed to incorporate herbicide-inhibiting point mutations
within the ALS1 locus. Transformed events modified with GVRs held point mutations
that were capable of supporting a reduced herbicide susceptibility phenotype,
while events transformed with conventional T-DNAs held no detectable mutations
and were similar to wild-type. Regeneration of transformed events improved
detection of point mutations that supported a stronger reduced herbicide
susceptibility phenotype. These results demonstrate the use of geminiviruses for
delivering genome editing reagents in plant species, and a novel approach to gene
targeting in a vegetatively propagated species.
PMID- 27493651
TI - Multigenic Control of Pod Shattering Resistance in Chinese Rapeseed Germplasm
Revealed by Genome-Wide Association and Linkage Analyses.
AB - The majority of rapeseed cultivars shatter seeds upon maturity especially under
hot-dry and windy conditions, reducing yield and gross margin return to growers.
Here, we identified quantitative trait loci (QTL) for resistance to pod shatter
in an unstructured diverse panel of 143 rapeseed accessions, and two structured
populations derived from bi-parental doubled haploid (DH) and inter-mated (IF2)
crosses derived from R1 (resistant to pod shattering) and R2 (prone to pod
shattering) accessions. Genome-wide association analysis identified six
significant QTL for resistance to pod shatter located on chromosomes A01, A06,
A07, A09, C02, and C05. Two of the QTL, qSRI.A09 delimited with the SNP marker Bn
A09-p30171993 (A09) and qSRI.A06 delimited with the SNP marker Bn-A06-p115948
(A06) could be repeatedly detected across environments in a diversity panel, DH
and IF2 populations, suggesting that at least two loci on chromosomes A06 and A09
were the main contributors to pod shatter resistance in Chinese germplasm.
Significant SNP markers identified in this study especially those that appeared
repeatedly across environments provide a cost-effective and an efficient method
for introgression and pyramiding of favorable alleles for pod shatter resistance
via marker-assisted selection in rapeseed improvement programs.
PMID- 27493652
TI - Multiple Evolutionary Events Involved in Maintaining Homologs of Resistance to
Powdery Mildew 8 in Brassica napus.
AB - The Resistance to Powdery Mildew 8 (RPW8) locus confers broad-spectrum resistance
to powdery mildew in Arabidopsis thaliana. There are four Homologous to RPW8s
(BrHRs) in Brassica rapa and three in Brassica oleracea (BoHRs). Brassica napus
(Bn) is derived from diploidization of a hybrid between B. rapa and B. oleracea,
thus should have seven homologs of RPW8 (BnHRs). It is unclear whether these
genes are still maintained or lost in B. napus after diploidization and how they
might have been evolved. Here, we reported the identification and sequence
polymorphisms of BnHRs from a set of B. napus accessions. Our data indicated that
while the BoHR copy from B. oleracea is highly conserved, the BrHR copy from B.
rapa is relatively variable in the B. napus genome owing to multiple evolutionary
events, such as gene loss, point mutation, insertion, deletion, and intragenic
recombination. Given the overall high sequence homology of BnHR genes, it is not
surprising that both intragenic recombination between two orthologs and two
paralogs were detected in B. napus, which may explain the loss of BoHR genes in
some B. napus accessions. When ectopically expressed in Arabidopsis, a C
terminally truncated version of BnHRa and BnHRb, as well as the full length BnHRd
fused with YFP at their C-termini could trigger cell death in the absence of
pathogens and enhanced resistance to powdery mildew disease. Moreover,
subcellular localization analysis showed that both BnHRa-YFP and BnHRb-YFP were
mainly localized to the extra-haustorial membrane encasing the haustorium of
powdery mildew. Taken together, our data suggest that the duplicated BnHR genes
might have been subjected to differential selection and at least some may play a
role in defense and could serve as resistance resource in engineering disease
resistant plants.
PMID- 27493653
TI - Comparative Transcriptome Analysis Revealed Genes Commonly Responsive to Varied
Nitrate Stress in Leaves of Tibetan Hulless Barley.
AB - Nitrogen (N) deprivation or excess can lead to dramatic phenotype change, disrupt
important biological processes, and ultimately limit plant productivity. To
explore genes in Tibetan hulless barley responsive to varied N stress, we
utilized a comparative transcriptomics method to investigate gene expression
patterns under three nitrate treatments. The transcriptome of the control
(optimal-nitrate, ON) sample was compared with that of free-nitrate (FN), low
nitrate (LN), and high-nitrate (HN) treatment samples, identifying 2428, 1274,
and 1861 genes, respectively, that exhibited significant differences in
transcript abundance. Among these, 9 genes encoding ribulose bisphosphate
carboxylases exhibited up-regulated expression under varied N stress. We further
compared FN vs. ON and LN vs. ON to investigate the impact of stress degree on
gene expression. With the aggravation of stress, more genes were differentially
expressed and thus possibly involved in the response to nitrogen deficiency.
Cluster and functional enrichment analysis indicated that the differentially
expressed genes (DEGs) in FN were highly enriched in response to stress, defense
response, and gene expression regulation. Comprehensive comparison analysis
further suggested that Tibetan hulless barley could respond to varied N stress by
regulating multiple common biological processes and pathways such as nitrogen
metabolism, carbon metabolism, and photosynthesis. A large number of specific
DEGs involved in diverse biological processes were also detected, implying
differences in the potential regulatory patterns of low- and high-N stress
response. Notably, we also identified some NIN-like proteins and other
transcription factors significantly modulated by these stresses, suggesting the
involvement of these transcription factors in N stress response. To our
knowledge, this study is the first investigation of the Tibetan hulless barley
transcriptome under N stress. The identified N-stress-related genes may provide
resources for genetic improvement and promote N use efficiency.
PMID- 27493654
TI - A Tree-Centered Approach to Assess Impacts of Extreme Climatic Events on Forests.
PMID- 27493656
TI - Sm-Like Protein-Mediated RNA Metabolism Is Required for Heat Stress Tolerance in
Arabidopsis.
AB - Sm-like proteins play multiple functions in RNA metabolism, which is essential
for biological processes such as stress responses in eukaryotes. The Arabidopsis
thaliana sad1 mutant has a mutation of sm-like protein 5 (LSM5) and shows
impaired drought and salt stress tolerances. The lsm5/sad1 mutant also showed
hypersensitivity to heat stress. GFP-fused LSM5/SAD1 was localized in the nucleus
under optimal growth conditions. After heat stress treatment, GFP-fused LSM5/SAD1
fluorescence was also observed as small cytoplasmic dots, in addition to nuclear
localization. Whole genome transcriptome analysis revealed that many genes in
Arabidopsis were drastically changed in response to heat stress. More heat
responsive genes were highly expressed in lsm5/sad1 mutant at both 2 and 6 h
after heat stress treatment. Additionally, intron-retained and capped transcripts
accumulated in the lsm5/sad1 mutant after heat stress treatment. In this study,
we also identified non-Arabidopsis Genome Initiative transcripts that were
expressed from unannotated regions. Most of these transcripts were antisense
transcripts, and many capped non-AGI transcripts accumulated in the lsm5/sad1
mutant during heat stress treatment. These results indicated that LSM5/SAD1
functions to degrade aberrant transcripts through appropriate mRNA splicing and
decapping, and precise RNA metabolic machinery is required for heat stress
tolerance.
PMID- 27493655
TI - Molecular Evolution and Association of Natural Variation in ZmARF31 with Low
Phosphorus Tolerance in Maize.
AB - Low-phosphorus (P) stress is one of the major factors constraining plant growth
and yield. Improving plant tolerance to P starvation through molecular breeding
is an efficient alternative to increase grain production. In the study, 331
diverse maize inbreds were used to detect nucleotide diversity and favorable
alleles of ZmARF31, which plays a key role in low P responses and root
architecture regulation. Significant phenotypic variation was found in each of 11
tested traits under both P and no-P treatments, and 30 single nucleotide
polymorphisms (SNPs) and 14 insertion-deletions (InDels) were detected in ZmARF31
among the 331 maize inbreds. The 5'-untranslated region (UTR) of ZmARF31 showed a
small linkage disequilibrium (LD) block under significant purifying selection,
whereas the 3'-UTR showed the most abundant diversity and a larger LD block.
Thirty, fourteen, and nine natural variations were identified in ZmARF31 that
were associated with P-deficiency-tolerance traits (P <= 0.01) by using the
general linear model (GLM), GLM incorporated with population structure, and mixed
linear model, respectively. Four SNPs were significantly associated with the
total dry weight (TDW) in the three models, of which SNPs S410 and S462 were
located in a complete LD block. A further verification conducted in a recombinant
inbred line population revealed that favorable allele G/G of non-synonymous
mutation S410 and favorable allele with a 38 bp insertion of InDel S1442
exhibited positive genetic effects on the TDW and total root tips, respectively.
Expression analysis further confirmed that ZmARF31 was highly expressed in the
roots of low-P-tolerant inbred 178. The protein encoded by ZmARF31 was located
both in the nucleus and cytoplasm. Haplotypes carrying more favorable alleles
showed a greater effect on phenotypic variation than single loci. Such haplotypes
should be helpful to develop valuable genetic markers and perform maize molecular
breeding.
PMID- 27493657
TI - De novo Assembly and Characterization of the Transcriptome of Broomcorn Millet
(Panicum miliaceum L.) for Gene Discovery and Marker Development.
AB - Broomcorn millet (Panicum miliaceum L.) is one of the world's oldest cultivated
cereals, which is well-adapted to extreme environments such as drought, heat, and
salinity with an efficient C4 carbon fixation. Discovery and identification of
genes involved in these processes will provide valuable information to improve
the crop for meeting the challenge of global climate change. However, the lack of
genetic resources and genomic information make gene discovery and molecular
mechanism studies very difficult. Here, we sequenced and assembled the
transcriptome of broomcorn millet using Illumina sequencing technology. After
sequencing, a total of 45,406,730 and 51,160,820 clean paired-end reads were
obtained for two genotypes Yumi No. 2 and Yumi No. 3. These reads were mixed and
then assembled into 113,643 unigenes, with the length ranging from 351 to 15,691
bp, of which 62,543 contings could be assigned to 315 gene ontology (GO)
categories. Cluster of orthologous groups and Kyoto Encyclopedia of Genes and
Genomes (KEGG) analyses assigned could map 15,514 unigenes into 202 KEGG pathways
and 51,020 unigenes to 25 COG categories, respectively. Furthermore, 35,216
simple sequence repeats (SSRs) were identified in 27,055 unigene sequences, of
which trinucleotides were the most abundant repeat unit, accounting for 66.72% of
SSRs. In addition, 292 differentially expressed genes were identified between the
two genotypes, which were significantly enriched in 88 GO terms and 12 KEGG
pathways. Finally, the expression patterns of four selected transcripts were
validated through quantitative reverse transcription polymerase chain reaction
analysis. Our study for the first time sequenced and assembled the transcriptome
of broomcorn millet, which not only provided a rich sequence resource for gene
discovery and marker development in this important crop, but will also facilitate
the further investigation of the molecular mechanism of its favored agronomic
traits and beyond.
PMID- 27493658
TI - A R2R3-MYB Transcription Factor Regulates the Flavonol Biosynthetic Pathway in a
Traditional Chinese Medicinal Plant, Epimedium sagittatum.
AB - Flavonols as plant secondary metabolites with vital roles in plant development
and defense against UV light, have been demonstrated to be the main bioactive
components (BCs) in the genus Epimedium plants, several species of which are used
as materials for Herba Epimedii, an important traditional Chinese medicine. The
flavonol biosynthetic pathway genes had been already isolated from Epimedium
sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis
has not been functionally characterized so far in Epimedium plants. In this
study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1
involved in regulation of the flavonol biosynthetic pathway from E. sagittatum.
Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB
family which contains the flavonol-specific MYB regulators identified to date.
Transient reporter assay showed that EsMYBF1 strongly activated the promoters of
EsF3H (flavanone 3-hydroxylase) and EsFLS (flavonol synthase), but not the
promoters of EsDFRs (dihydroflavonol 4-reductase) and EsANS (anthocyanidin
synthase) in transiently transformed Nicotiana benthamiana leaves. Both yeast two
hybrid assay and transient reporter assay validated EsMYBF1 to be independent of
EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic
expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol
content and the decreased anthocyanin content in flowers. Correspondingly, the
structural genes involved in flavonol synthesis were upregulated in the EsMYBF1
overexpression lines, including NtCHS (chalcone synthase), NtCHI (chalcone
isomerase), NtF3H and NtFLS, whereas the late biosynthetic genes of the
anthocyanin pathway (NtDFR and NtANS) were remarkably downregulated, compared to
the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB
regulator, and involved in regulation of the biosynthesis of the flavonol-derived
BCs in E. sagittatum. Thus, identification and functional characterization of
EsMYBF1 provide insight into understanding the biosynthesis and regulation of the
flavonol-derived BCs in Epimedium plants, and also provide an effective tool gene
for genetic manipulation to improve the flavonol synthesis.
PMID- 27493660
TI - Lack of Association Found between Helicobacter pylori Infection and Diarrhea
Predominant Irritable Bowel Syndrome: A Multicenter Retrospective Study.
AB - Aims. The association between Helicobacter pylori (H. pylori) infection and
diarrhea-predominant irritable bowel syndrome (IBS-D) is still controversial.
Here we performed a retrospective study to explore this issue. Methods. A total
of 502 inpatients with Rome III confirmed IBS-D and known H. pylori status from 8
hospitals were enrolled. H. pylori-positive patients, hospitalized in the recent
year, were followed up to evaluate the effects of H. pylori eradication on IBS-D
clinical course. Results. Of the 502 IBS-D patients, 206 were H. pylori-positive,
with an infection rate that has no significant difference with that of the
general population in Guangdong province (p = 0.348). For patients followed up,
no significant differences were noted as to overall symptoms (p = 0.562),
abdominal pain/discomfort (p = 0.777), bloating (p = 0.736), stool frequency (p =
0.835), or stool characteristics (p = 0.928) between the H. pylori-eradicated
group and the control group. The results were the same in long-term follow-up
patients except the improvement of bloating, which showed that the bloating score
in the H. pylori-eradicated group was significantly lower (p = 0.047).
Conclusions. No significant correlation between H. pylori infection and IBS-D was
noted. Overall, IBS-D patients may not benefit from H. pylori eradication.
PMID- 27493661
TI - Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with
Intestinal Oxidative Stress Injury.
AB - Background. To investigate whether intestinal mucosal barrier was damaged or not
in chronic kidney disease progression and the status of oxidative stress.
Methods. Rats were randomized into two groups: a control group and a uremia
group. The uremia rat model was induced by 5/6 kidney resection. In postoperative
weeks (POW) 4, 6, 8, and 10, eight rats were randomly selected from each group to
prepare samples for assessing systemic inflammation, intestinal mucosal barrier
changes, and the status of intestinal oxidative stress. Results. The uremia group
presented an increase trend over time in the serum tumor necrosis factor-alpha,
interleukin-6 (IL-6) and IL-10, serum D-lactate and diamine oxidase, and
intestinal permeability, and these biomarkers were significantly higher than
those in control group in POW 8 and/or 10. Chiu's scores in uremia group were
also increased over time, especially in POW 8 and 10. Furthermore, the intestinal
malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were
significantly higher in uremia group when compared with those in control group in
POW 8 and/or 10. Conclusions. The advanced chronic kidney disease could induce
intestinal mucosal barrier damage and further lead to systemic inflammation. The
underlying mechanism may be associated with the intestinal oxidative stress
injury.
PMID- 27493662
TI - A Clinicopathological Profile of Prostate Cancer in Trinidad and Tobago.
AB - Aim. To conduct a clinicopathological review of all prostate biopsies performed
in a tertiary referral centre in Trinidad and Tobago over a period of 30 months.
Methods. The records of all patients who had prostate biopsies from January 2012
to July 2014 were reviewed. Clinical and pathologic data were compiled and
subsequently analysed using SPSS version 20. Results. From January 2012 to July
2014, 617 transrectal ultrasound guided prostate biopsies were performed.
Pathological data were found for 546 patients of whom 283 (51.8%) were confirmed
carcinoma of the prostate. Moderately differentiated tumors (Gleason 7) were the
most common group. Using the D'Amico risk classification, most cases were found
to be high risk (63.1%). Afro-Trinidadians comprised 72.1% of the patients with
prostate cancer. Afro-Trinidadians were also more likely to have high risk and
high grade disease as well as high PSA values. Conclusion. This study
demonstrates that over half of our biopsies are eventually positive for cancer
and most cases were high risk. Afro-Trinidadians comprised a disproportionate
number of those diagnosed with prostate cancer and had a greater risk of high
risk disease.
PMID- 27493663
TI - Does Frailty Predict Health Care Utilization in Community-Living Older Romanians?
AB - Background. The predictive value of frailty assessment is still debated. We
analyzed the predictive value of frailty of independent living elderly. The
outcomes variables were visits to the general practitioner, hospital admission,
and occurrence of new health problems. Methods. A one-year follow-up study was
executed among 215 community-living old Romanians. General practitioners reported
the outcome variables of patients, whose frailty was assessed one year before,
using the Groningen Frailty Indicator. The predictive validity is analyzed by
descriptive and regression analysis. Results. Three-quarters of all participants
visited their general practitioner three times more last year and one-third were
at least once admitted to a hospital. Patients who scored frail one year before
were more often admitted to a hospital. Visits to the general practitioner and
occurrence of new health problems were not statistically significant related to
frailty scores. The frailty items polypharmacy, social support, and activities in
daily living were associated with adverse outcomes. Conclusions. The predictive
value of frailty instruments as the Groningen Frailty Indicator is still limited.
More research is needed to predict health outcomes, health care utilization, and
quality of life of frailty self-assessment instruments. Validation research on
frailty in different "environments" is recommended to answer the question to what
extent contextual characteristics influence the predictive value.
PMID- 27493659
TI - Maintaining Genome Stability in Defiance of Mitotic DNA Damage.
AB - The implementation of decisions affecting cell viability and proliferation is
based on prompt detection of the issue to be addressed, formulation and
transmission of a correct set of instructions and fidelity in the execution of
orders. While the first and the last are purely mechanical processes relying on
the faithful functioning of single proteins or macromolecular complexes (sensors
and effectors), information is the real cue, with signal amplitude, duration, and
frequency ultimately determining the type of response. The cellular response to
DNA damage is no exception to the rule. In this review article we focus on DNA
damage responses in G2 and Mitosis. First, we set the stage describing mitosis
and the machineries in charge of assembling the apparatus responsible for
chromosome alignment and segregation as well as the inputs that control its
function (checkpoints). Next, we examine the type of issues that a cell
approaching mitosis might face, presenting the impact of post-translational
modifications (PTMs) on the correct and timely functioning of pathways correcting
errors or damage before chromosome segregation. We conclude this essay with a
perspective on the current status of mitotic signaling pathway inhibitors and
their potential use in cancer therapy.
PMID- 27493664
TI - A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine
Parameters and Insulin Resistance in PCOS Young Overweight Women.
AB - Introduction. We evaluated the effects of a therapy that combines myo-inositol
(MI) and D-chiro-inositol (DCI) in young overweight women affected by polycystic
ovary syndrome (PCOS), characterized by oligo- or anovulation and
hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46
patients affected by PCOS and, randomly, we assigned them to two groups, A and B,
treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or
with placebo (folic acid) for six months. Thus, we analyzed pretreatment and
posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin,
androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index,
and fasting glucose and insulin. Results. We recorded a statistically significant
reduction of LH, free testosterone, fasting insulin, and HOMA index only in the
group treated with the combined therapy of MI plus DCI; in the same patients, we
observed a statistically significant increase of 17-beta-Estradiol levels.
Conclusions. The combined therapy of MI plus DCI is effective in improving
endocrine and metabolic parameters in young obese PCOS affected women.
PMID- 27493665
TI - From Guided Surgery to Final Prosthesis with a Fully Digital Procedure: A
Prospective Clinical Study on 15 Partially Edentulous Patients.
AB - Scope. To demonstrate guided implant placement and the application of fixed,
implant-supported prosthetic restorations with a fully digital workflow. Methods.
Over a 2-year period, all patients with partial edentulism of the posterior
maxilla, in need of fixed implant-supported prostheses, were considered for
inclusion in this study. The protocol required intraoral scanning and cone beam
computed tomography (CBCT), the superimposition of dental-gingival information on
bone anatomy, surgical planning, 3D-printed teeth-supported surgical templates,
and modelling and milling of polymethylmethacrylate (PMMA) temporaries for
immediate loading. After 3 months, final optical impression was taken and milled
zirconia frameworks and 3D-printed models were fabricated. The frameworks were
veneered with ceramic and delivered to the patients. Results. Fifteen patients
were selected for this study. The surgical templates were stable. Thirty implants
were placed (BTK Safe(r), BTK, Vicenza, Italy) and immediately loaded with PMMA
temporaries. After 3 months, the temporaries were replaced by the final
restorations in zirconia-ceramic, fabricated with a fully digital process. At 6
months, none of the patients reported any biological or functional problems with
the implant-supported prostheses. Conclusions. The present procedure for fully
digital planning of implants and short-span fixed implant-supported restorations
has been shown to be reliable. Further studies are needed to validate these
results.
PMID- 27493666
TI - Characterization and Uncertainty Assessment of a Certified Reference Material of
Chloramphenicol in Methanol (GBW(E)082557).
AB - Prior to preparation of CRM candidate of chloramphenicol in methanol with a
concentration of 100 mg/L, two independent methods including mass balance (MB)
and quantitative nuclear magnetic resonance (qNMR) were employed to precisely
measure the mass fraction of pure chloramphenicol materials. The mass fraction
was assigned to be 99.8% with uncertainty of 0.3%. Homogeneity testing and
stability study of chloramphenicol in methanol were examined by using high
performance liquid chromatography. Additionally, the uncertainties originating
from the process of CRM development were comprehensively evaluated. The
experimental results indicate that the property value of this CRM is homogeneous
and stable at 4 degrees C for at least six months. The new CRM (GBW(E)082557) can
be applicable to calibration of instrument and assurance of accuracy and
comparability of results in routine measurement.
PMID- 27493667
TI - Severity of Osteoarthritis Is Associated with Increased Arterial Stiffness.
AB - Objective. Osteoarthritis (OA) is associated with increased cardiovascular
comorbidity and mortality. Evidence is lacking about whether arterial stiffness
is involved in OA. The objective of our study was to find out associations
between OA, arterial stiffness, and adipokines. Design. Seventy end-stage knee
and hip OA patients (age 62 +/- 7 years) and 70 asymptomatic controls (age 60 +/-
7 years) were investigated using the applanation tonometry to determine their
parameters of arterial stiffness. Serum adiponectin, leptin, and matrix
metalloproteinase 3 (MMP-3) levels were determined using the ELISA method.
Correlation between variables was determined using Spearman's rho. Multiple
regression analysis with a stepwise selection procedure was employed. Results.
Radiographic OA grade was positively associated with increased carotid-femoral
pulse wave velocity (cf-PWV) (r = 0.272, p = 0.023). We found that OA grade was
also associated with leptin and MMP-3 levels (rho = -0.246, p = 0.040 and rho =
0.235, p = 0.050, resp.). In addition, serum adiponectin level was positively
associated with augmentation index and inversely with large artery elasticity
index (rho = 0.293, p = 0.006 and rho = -0.249, p = 0.003, resp.). Conclusions.
Our results suggest that OA severity is independently associated with increased
arterial stiffness and is correlated with expression of adipokines. Thus,
increased arterial stiffness and adipokines might play an important role in
elevated cardiovascular risk in end-stage OA.
PMID- 27493668
TI - Differentiation of Human Adipose Derived Stem Cells into Smooth Muscle Cells Is
Modulated by CaMKIIgamma.
AB - The multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is
known to participate in maintenance and switches of smooth muscle cell (SMC)
phenotypes. However, which isoform of CaMKII is involved in differentiation of
adult mesenchymal stem cells into contractile SMCs remains unclear. In the
present study, we detected gamma isoform of CaMKII in differentiation of human
adipose derived stem cells (hASCs) into SMCs that resulted from treatment with
TGF-beta1 and BMP4 in combination for 7 days. The results showed that CaMKIIgamma
increased gradually during differentiation of hASCs as determined by real-time
PCR and western blot analysis. The siRNA-mediated knockdown of CaMKIIgamma
decreased the protein levels and transcriptional levels of smooth muscle
contractile markers (a-SMA, SM22a, calponin, and SM-MHC), while CaMKIIgamma
overexpression increases the transcriptional and protein levels of smooth muscle
contractile markers. These results suggested that gamma isoform of CaMKII plays a
significant role in smooth muscle differentiation of hASCs.
PMID- 27493670
TI - Effects of Forest Bathing on Cardiovascular and Metabolic Parameters in Middle
Aged Males.
AB - In the present study, we investigated the effects of a forest bathing on
cardiovascular and metabolic parameters. Nineteen middle-aged male subjects were
selected after they provided informed consent. These subjects took day trips to a
forest park in Agematsu, Nagano Prefecture, and to an urban area of Nagano
Prefecture as control in August 2015. On both trips, they walked 2.6 km for 80
min each in the morning and afternoon on Saturdays. Blood and urine were sampled
before and after each trip. Cardiovascular and metabolic parameters were
measured. Blood pressure and pulse rate were measured during the trips. The
Japanese version of the profile of mood states (POMS) test was conducted before,
during, and after the trips. Ambient temperature and humidity were monitored
during the trips. The forest bathing program significantly reduced pulse rate and
significantly increased the score for vigor and decreased the scores for
depression, fatigue, anxiety, and confusion. Urinary adrenaline after forest
bathing showed a tendency toward decrease. Urinary dopamine after forest bathing
was significantly lower than that after urban area walking, suggesting the
relaxing effect of the forest bathing. Serum adiponectin after the forest bathing
was significantly greater than that after urban area walking.
PMID- 27493669
TI - Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis
Precursors?
AB - The relationship between tumor initiation and tumor progression can follow a
linear projection in which all tumor cells are equally endowed with the ability
to progress into metastasis. Alternatively, not all tumor cells are equal
genetically and/or epigenetically, and only few cells are induced to become
metastatic tumor cells. The location of these cells within the tumor can also
impact the fate of these cells. The most inner core of a tumor where an elevated
pressure of adverse conditions forms, such as necrosis-induced inflammation and
hypoxia-induced immunosuppressive environment, seems to be the most fertile
ground to generate such tumor cells with metastatic potential. Here we will call
this necrotic/hypoxic core the "aggressiveness niche" and will present data to
support its involvement in generating these metastatic precursors. Within this
niche, interaction of hypoxia-surviving cells with the inflammatory
microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs),
tumor-associated macrophages (TAMs), and other types of cells and the
establishment of bidirectional interactions between them elevate the
aggressiveness of these tumor cells. Additionally, immune evasion properties
induced in these cells most likely contribute in the formation and maintenance of
such aggressiveness niche.
PMID- 27493671
TI - Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of
Macrophage Polarization.
AB - Antitumor effect of berberine has been reported in a wide spectrum of cancer,
however, the mechanisms of which are not fully understood. The aim of this study
was to investigate the hypothesis that berberine suppresses tumorigenesis in the
familial adenomatous polyposis (FAP) by regulating the macrophage polarization in
Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks.
Primary macrophages were isolated; after berberine treatment, the change in
signaling cascade was determined. The total number and size of polyps were
reduced remarkably in berberine group, compared with control group. A significant
decrease in protein levels of F4/80, mannose receptor (MR), and COX-2 in stroma
of intestinal polyps and an increase in the level of iNOS were observed after
berberine treatment. The mRNA level of MR and Arg-1 in berberine group was
significantly lower than those in IL-10 or IL-4 group, while no significant
difference in mRNA levels of iNOS and CXCL10 was observed. The migration and
invasiveness assays in vitro showed that berberine could reduce the capability of
migration and invasiveness. These findings suggest that berberine attenuates
intestinal tumorigenesis by inhibiting the migration and invasion of colorectal
tumor cells via regulation of macrophage polarization.
PMID- 27493673
TI - Antitumor Effect of Zhihuang Fuzheng Soft Capsules on Tumor-Bearing Mice.
AB - Chinese medicines (CMs) have been shown to have some advantages in preventing and
controlling tumors. In this study, we investigated the antitumor effect of ZFSC
by establishing a mouse model of HT-1080, A-549, and HCT-8 tumors. The result
showed that tumor volumes of HT-1080 tumor-bearing nude mice in ZFSC low, medium,
and high dose groups were lower significantly compared to the model group, and
the high dose ZFSC showed the best antitumor effect. Tumor volumes of A-549 tumor
bearing nude mice in ZFSC low, medium, and high dose groups were lower
significantly compared to the model group and showed a good dose-response
relationship. There was no significant effect on human colon cancer, although
inhibition trends disappeared in the bar chart. In order to verify the
immunomodulatory effect of ZFSC, ELISA was used to analyze serums IL-2, TNF
alpha, and IFN in spleens. The results showed that ZFSC could enhance the immune
function of tumor-bearing mice. ZFSC reduced IFN-gamma and TNF-alpha content in
the serum of HT-1080 tumor-bearing mice and inhibit PD1 and PDL1 and suggested
that the antitumor mechanism of ZFSC on human fibrosarcoma could be attributed to
inhibition of the PDL1/PD1 pathway.
PMID- 27493672
TI - Unsweetened Natural Cocoa Powder Has the Potential to Attenuate High Dose
Artemether-Lumefantrine-Induced Hepatotoxicity in Non-Malarious Guinea Pigs.
AB - Objective. This study investigated the elemental composition of unsweetened
natural cocoa powder (UNCP), its effect on nitric oxide, and its hepatoprotective
potential during simultaneous administration with high-dose
artemether/lumefantrine (A/L). Method. Macro- and microelements in UNCP were
analyzed with EDXRF spectroscopy. Thirty (30) male guinea-pigs were then divided
into five groups. For groups 3 (low-dose), 4 (medium-dose), and 5 (high-dose),
the animals received oral UNCP prophylactically for 14 days. Group 1 received
distilled water (14 days) and group 2 A/L for the last 3 days (days 12 to 14).
After euthanisation, biochemical and histopathological examinations were carried
out in all groups. Results. Phytochemical analysis of UNCP showed the presence of
saponins, flavonoids, tannins, and cardiac glycosides. Thirty-eight (38) macro-
and microelements were found. UNCP produced significant decreases in ALT, ALP,
GGT, and AST levels. A significant increase in total protein levels was observed
during A/L+UNCP administration in comparison to 75 mg/kg A/L group.
Histopathological examinations buttressed the protective effects of cocoa
administration. UNCP administration increased nitric oxide levels 149.71% (P <
0.05) compared to controls. Conclusion. UNCP increases nitric oxide levels and
has hepatoprotective potential during A/L administration. A high level of copper
was observed which may be detrimental during high daily consumptions of UNCP.
PMID- 27493674
TI - Chitosan and Sodium Alginate Combinations Are Alternative, Efficient, and Safe
Natural Adjuvant Systems for Hepatitis B Vaccine in Mouse Model.
AB - Hepatitis B viral (HBV) infections represent major public health problem and are
an occupational hazard for healthcare workers. Current alum-adjuvanted HBV
vaccine is the most effective measure to prevent HBV infection. However, the
vaccine has some limitations including poor response in some vaccinee and being a
frost-sensitive suspension. The goal of our study was to use an alternative
natural adjuvant system strongly immunogenic allowing for a reduction in dose and
cost. We tested HBV surface antigen (HBsAg) adjuvanted with chitosan (Ch) and
sodium alginate (S), both natural adjuvants, either alone or combined with alum
in mouse model. Mice groups were immunized subcutaneously with HBsAg adjuvanted
with Ch or S, or triple adjuvant formula with alum (Al), Ch, and S, or double
formulations with AlCh or AlS. These were compared to control groups immunized
with current vaccine formula or unadjuvanted HBsAg. We evaluated the rate of
seroconversion, serum HBsAg antibody, IL-4, and IFN-gamma levels. The results
showed that the solution formula with Ch or S exhibited comparable immunogenic
responses to Al-adjuvanted suspension. The AlChS gave significantly higher
immunogenic response compared to controls. Collectively, our results indicated
that Ch and S are effective HBV adjuvants offering natural alternatives,
potentially reducing dose.
PMID- 27493675
TI - Spirituality Concept by Health Professionals in Iran: A Qualitative Study.
AB - Background. For years, researchers have sought to provide a clear definition of
spirituality and its features and consequences, but the definitions provided of
this concept still lack transparency. The present qualitative research was
conducted to clarify this concept within the religious-cultural context of Iran.
Materials and Methods. The present conventional qualitative content analysis was
conducted with an inductive approach. Data were collected through semistructured
interviews with 17 spiritual health experts and activists selected through
purposive sampling. Results. Three themes emerged from the analysis of the data,
including (1) the structure of spirituality, (2) defects in the conceptualization
of spirituality, and (3) spirituality in practice, which are explained in this
paper with their relevant subthemes and codes. The definition which this study
proposes for this concept is that "spirituality is the sublime aspect of human
existence bestowed on all humans in order for them to traverse the path of
transcendence that is closeness to God (Allah)." Conclusion. The definition
provided by this study is similar to the previous definitions of this concept in
its main part (transcendence) and in incorporating a God-centered view of
spirituality within the context of an Islamic society. This definition has
implications for health services' education, research, and practice in similar
societies.
PMID- 27493676
TI - Ethnobotany: A Living Science for Alleviating Human Suffering.
PMID- 27493679
TI - Development of a universal and simplified ddRAD library preparation approach for
SNP discovery and genotyping in angiosperm plants.
AB - BACKGROUND: The double digest restriction-site associated DNA sequencing
technology (ddRAD-seq) is a reduced representation sequencing technology by
sampling genome-wide enzyme loci developed on the basis of next-generation
sequencing. ddRAD-seq has been widely applied to SNP marker development and
genotyping on animals, especially on marine animals as the original ddRAD
protocol is mainly built and trained based on animal data. However, wide
application of ddRAD-seq technology in plant species has not been achieved so
far. Here, we aim to develop an optimized ddRAD library preparation protocol be
accessible to most angiosperm plant species without much startup pre-experiment
and costs. RESULTS: We first tested several combinations of enzymes by in silico
analysis of 23 plant species covering 17 families of angiosperm and 1 family of
bryophyta and found AvaII + MspI enzyme pair produced consistently higher number
of fragments in a broad range of plant species. Then we removed two purifying and
one quantifying steps of the original protocol, replaced expensive consumables
and apparatuses by conventional experimental apparatuses. Besides, we shortened
P1 adapter from 37 to 25 bp and designed a new barcode-adapter system containing
20 pairs of barcodes of varying length. This is an optimized ddRAD strategy for
angiosperm plants that is economical, time-saving and requires little technical
expertise or investment in laboratory equipment. We refer to this simplified
protocol as MiddRAD and we demonstrated the utility and flexibility of our
approach by resolving phylogenetic relationships of two genera of woody bamboos
(Dendrocalamus and Phyllostachys). Overall our results provide empirical evidence
for using this method on different model and non-model plants to produce
consistent data. CONCLUSIONS: As MiddRAD adopts an enzyme pair that works for a
broad range of angiosperm plants, simplifies library constructing procedure and
requires less DNA input, it will greatly facilitate designing a ddRAD project.
Our optimization of this method may make ddRAD be widely used in fields of plant
population genetics, phylogenetics, phylogeography and molecular breeding.
PMID- 27493678
TI - Detecting N-myristoylation and S-acylation of host and pathogen proteins in
plants using click chemistry.
AB - BACKGROUND: The plant plasma membrane is a key battleground in the war between
plants and their pathogens. Plants detect the presence of pathogens at the plasma
membrane using sensor proteins, many of which are targeted to this lipophilic
locale by way of fatty acid modifications. Pathogens secrete effector proteins
into the plant cell to suppress the plant's defense mechanisms. These effectors
are able to access and interfere with the surveillance machinery at the plant
plasma membrane by hijacking the host's fatty acylation apparatus. Despite the
important involvement of protein fatty acylation in both plant immunity and
pathogen virulence mechanisms, relatively little is known about the role of this
modification during plant-pathogen interactions. This dearth in our understanding
is due largely to the lack of methods to monitor protein fatty acid modifications
in the plant cell. RESULTS: We describe a rapid method to detect two major forms
of fatty acylation, N-myristoylation and S-acylation, of candidate proteins using
alkyne fatty acid analogs coupled with click chemistry. We applied our approach
to confirm and decisively demonstrate that the archetypal pattern recognition
receptor FLS2, the well-characterized pathogen effector AvrPto, and one of the
best-studied intracellular resistance proteins, Pto, all undergo plant-mediated
fatty acylation. In addition to providing a means to readily determine fatty
acylation, particularly myristoylation, of candidate proteins, this method is
amenable to a variety of expression systems. We demonstrate this using both
Arabidopsis protoplasts and stable transgenic Arabidopsis plants and we leverage
Agrobacterium-mediated transient expression in Nicotiana benthamiana leaves as a
means for high-throughput evaluation of candidate proteins. CONCLUSIONS: Protein
fatty acylation is a targeting tactic employed by both plants and their
pathogens. The metabolic labeling approach leveraging alkyne fatty acid analogs
and click chemistry described here has the potential to provide mechanistic
details of the molecular tactics used at the host plasma membrane in the battle
between plants and pathogens.
PMID- 27493680
TI - Machine Learning Approach to Automated Quality Identification of Human Induced
Pluripotent Stem Cell Colony Images.
AB - The focus of this research is on automated identification of the quality of human
induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a
contemporary method by which the patient's cells are reprogrammed back to stem
cells and are differentiated to any cell type wanted. iPS cell technology will be
used in future to patient specific drug screening, disease modeling, and tissue
repairing, for instance. However, there are technical challenges before iPS cell
technology can be used in practice and one of them is quality control of growing
iPSC colonies which is currently done manually but is unfeasible solution in
large-scale cultures. The monitoring problem returns to image analysis and
classification problem. In this paper, we tackle this problem using machine
learning methods such as multiclass Support Vector Machines and several baseline
methods together with Scaled Invariant Feature Transformation based features. We
perform over 80 test arrangements and do a thorough parameter value search. The
best accuracy (62.4%) for classification was obtained by using a k-NN classifier
showing improved accuracy compared to earlier studies.
PMID- 27493681
TI - Anti-cholinesterases and memory improving effects of Vietnamese Xylia xylocarpa.
AB - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia among
the elderly and is characterized by loss of memory and other cognitive functions.
An increase in AChE (a key enzyme in the cholinergic nervous system) levels
around beta-amyloid plaques and neurofibrillary tangles is a common feature of AD
neuropathology. Amnesic effects of scopolamine (acetylcholine receptor
antagonist) can be investigated in various behavioral tests such as Morris water
maze, object recognition, Y-maze, and passive avoidance. In the scope of this
paper, we report the anti-AChE, anti-BChE properties of the isolated compound and
the in vivo effects of the methanolic extract of Xylia xylocarpa (MEXX) on
scopolamine-induced memory deficit. RESULTS: In further phytochemistry study, a
new hopan-type triterpenoid, (3beta)-hopan-3-ol-28,22-olide (1), together with
twenty known compounds were isolated (2-21). Compound 1, 2, 4, 5, 7-9, and 11-13
exhibited potent acetylcholinesterase (AChE) inhibitory activity in a
concentration-dependent manner with IC50 values ranging from 54.4 to 94.6 MUM.
Compound 13 was also shown anti-butyrylcholinesterase (BChE) activity with an
IC50 value of 42.7 MUM. The Morris water Y-maze, Y-maze, and object recognition
test were also carried out. CONCLUSIONS: It is noteworthy that MEXX is effective
when administered orally to mice, experimental results are consistent with the
traditional use of this medicinal plant species.
PMID- 27493677
TI - Chronic over-nutrition and dysregulation of GSK3 in diseases.
AB - Loss of cellular response to hormonal regulation in maintaining metabolic
homeostasis is common in the process of aging. Chronic over-nutrition may render
cells insensitive to such a hormonal regulation owing to overstimulation of
certain signaling pathways, thus accelerating aging and causing diseases. The
glycogen synthase kinase 3 (GSK3) plays a pivotal role in relaying various
extracellular and intracellular regulatory signals critical to cell growth,
survival, regeneration, or death. The main signaling pathway regulating GSK3
activity through serine-phosphorylation is the phosphoinositide 3-kinase
(PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/Akt relay that catalyzes serine
phosphorylation and thus inactivation of GSK3. In addition, perilipin 2 (PLIN2)
has recently been shown to regulate GSK3 activation through direct association
with GSK3. This review summarizes current understanding on environmental and
nutritional factors contributing to GSK3 regulation (or dysregulation) through
the PI3K/PDK1/Akt/GSK3 axis, and highlights the newly discovered role that PLIN2
plays in regulating GSK3 activity and GSK3 downstream pathways.
PMID- 27493682
TI - Simultaneous quantification of triterpenoic acids by high performance liquid
chromatography method in the extracts of gum resin of Boswellia serrata obtained
by different extraction techniques.
AB - BACKGROUND: Boswellia serrata, also known as Indian frankincense is a
commercially important medicinal plant which has been used for hundreds of years
as an Ayurvedic medicine for the attempted treatment of arthritis. It contains
naturally occurring triterpenoic acids, called as boswellic acids (BA's).
RESULTS: A highly reproducible High performance liquid chromatography-ultraviolet
diode array detection (HPLC-UV-DAD) method was developed for the simultaneous
determination and quantitative analysis of eight major triterpenoic acids in
Boswellia serrata gum resin obtained by different extraction techniques. All the
calibration curves exhibited good linear regression (R(2) > 0.997) within the
test ranges. The established method showed good precision and overall recoveries
of the boswellic acids. CONCLUSIONS: The eight triterpenoic acids coded as BS-1
(11-keto-beta-boswellic acid), BS-2 (3-O-acetyl-11-keto-beta-boswellic acid), BS
3 (3-keto tirucallic acid), BS-4 (3-O-acetyl-alpha-tirucallic acid), BS-5 (3-O
acetyl-beta-tirucallic acid), BS-6 (alpha-boswellic acid), BS-7 (beta-boswellic
acid) and BS-8 (3-O-acetyl-beta-boswellic acid) were isolated from the processed
gum resin of Boswellia serrata by column chromatography. The proposed HPLC method
is simple, reliable and has been very useful for the qualitative as well as
quantitative analysis of boswellic acids in the gum resin of Boswellia serrata.
The proposed method allows to quantify boswellic acids in appreciable amounts by
HPLC-UV (DAD) method in the extracts and the available marketed
formulations.Graphical abstractIsolation & separation of eight Triterpenoic acids
from Boswellia serrata.
PMID- 27493683
TI - Microwave assisted synthesis, antifungal activity, DFT and SAR study of 1,2,4
triazolo[4,3-a]pyridine derivatives containing hydrazone moieties.
AB - BACKGROUND: The increasing prevalence of multi-drug resistant fungal infections
has encouraged the search for new antifungal agents. Hydrazone derivatives always
exhibited diversity activities, including antifungal, anti-inflammatory, anti
oxidation, anti-cancer activity. Regarding the heterocyclic moiety, 1,2,4
triazolo[4,3-a]pyridine derivatives also display broad activities, such as
antifungal activity, anticonvulsant activity, herbicidal activity, antimicrobial
activity and anticancer activity. RESULTS: A series of novel 1,2,4-triazolo[4,3
a]pyridine derivatives containing hydrazone moiety were designed and synthesized
from 2,3-dichloropyridine, hydrazine hydrate by multi-step reactions under
microwave irradiation condition, and their structures were characterized by FT
IR, (1)H NMR, (13)C NMR, (19)F NMR, MS and elemental analysis. The antifungal
activities of title compounds were determined. The results indicated that some of
the title compounds exhibited good antifungal activity. Furthermore, DFT
calculation was carried out for studying the structure-activity relationship
(SAR). CONCLUSION: A practical synthetic route to obtain 1,2,4-triazolo[4,3
a]pyridine derivatives is presented. This study suggests that the 1,2,4
triazolo[4,3-a]pyridine derivatives exhibited good antifungal activity.
PMID- 27493684
TI - A school mental health literacy curriculum resource training approach: effects on
Tanzanian teachers' mental health knowledge, stigma and help-seeking efficacy.
AB - BACKGROUND: Mental health literacy (MHL) is foundational for mental health
promotion, prevention, stigma reduction, and care; School supported information
pertaining to MHL in sub-Saharan Africa is extremely limited, including in
Tanzania. Successful application of a school MHL curriculum resource may be an
effective way to increase teacher MHL and therefore help to improve mental health
outcomes for students. METHODS: Secondary school teachers in Tanzania were
trained on the African Guide (AG) a school MHL curriculum resource culturally
adapted from a Canadian MHL resource (The Guide) for use in Africa. Teacher
training workshops on the classroom application of the AG were used to evaluate
its impact on mental health literacy in a sample of Tanzanian Secondary school
teachers. Pre-post training assessment of participant knowledge and attitudes was
conducted. Help-seeking efficacy for teachers themselves and their interventions
for students, friends, family members and peers were determined. RESULTS: Paired
t test (n = 37) results demonstrate highly significant improvements in teacher's
overall knowledge (p < 0.001; d = 1.14), including mental health knowledge, (p <
0.001; d = 1.14) and curriculum specific knowledge (p < 0.01; d = 0.63).
Teachers' stigma against mental illness decreased significantly following the
training (p < 0.001; d = 0.61). Independent t tests comparing the paired sample
against unpaired sample also demonstrated significant differences between the
groups for teacher's overall knowledge (p < 0.001). Teachers also reported high
rates (greater than 3/4 of the sample) of positive help-seeking efficacy for
themselves as well as for their students, friends, family members and peers. As a
result of the training, the number of students teachers identified for potential
mental health care totaled over 200. CONCLUSIONS: These positive results, when
taken together with other research, suggest that the use of a classroom-based
resource (the AG) that integrates MHL into existing school curriculum through
training teachers may be an effective and sustainable way to increase the MHL
(improved knowledge, decreased stigma and positive help-seeking efficacy) of
teachers in Tanzania. As this study replicated the results of a previous
intervention in Malawi, consideration could be given to scaling up this
intervention in both countries and applying this resource and approach in other
countries in East Africa.
PMID- 27493685
TI - Effect of tungstate on acetate and ethanol production by the electrosynthetic
bacterium Sporomusa ovata.
AB - BACKGROUND: Microbial electrosynthesis (MES) and gas fermentation are bioenergy
technologies in which a microbial catalyst reduces CO2 into organic carbon
molecules with electrons from the cathode of a bioelectrochemical system or from
gases such as H2. The acetogen Sporomusa ovata has the capacity of reducing CO2
into commodity chemicals by both gas fermentation and MES. Acetate is often the
only product generated by S. ovata during autotrophic growth. RESULTS: In this
study, trace elements in S. ovata growth medium were optimized to improve MES and
gas fermentation productivity. Augmenting tungstate concentration resulted in a
2.9-fold increase in ethanol production by S. ovata during H2:CO2-dependent
growth. It also promoted electrosynthesis of ethanol in a S. ovata-driven MES
reactor and increased acetate production 4.4-fold compared to unmodified medium.
Furthermore, fatty acids propionate and butyrate were successfully converted to
their corresponding alcohols 1-propanol and 1-butanol by S. ovata during gas
fermentation. Increasing tungstate concentration enhanced conversion efficiency
for both propionate and butyrate. Gene expression analysis suggested that
tungsten-containing aldehyde ferredoxin oxidoreductases (AORs) and a tungsten
containing formate dehydrogenase (FDH) were involved in the improved biosynthesis
of acetate, ethanol, 1-propanol, and 1-butanol. AORs and FDH contribute to the
fatty acids re-assimilation pathway and the Wood-Ljungdahl pathway, respectively.
CONCLUSIONS: This study presented here shows that optimization of microbial
catalyst growth medium can improve productivity and lead to the biosynthesis of
different products by gas fermentation and MES. It also provides insights on the
metabolism of biofuels production in acetogens and demonstrates that S. ovata has
an important untapped metabolic potential for the production of other chemicals
than acetate via CO2-converting bioprocesses including MES.
PMID- 27493686
TI - Enhancement of cellulosome-mediated deconstruction of cellulose by improving
enzyme thermostability.
AB - BACKGROUND: The concerted action of three complementary cellulases from
Clostridium thermocellum, engineered to be stable at elevated temperatures, was
examined on a cellulosic substrate and compared to that of the wild-type enzymes.
Exoglucanase Cel48S and endoglucanase Cel8A, both key elements of the natural
cellulosome from this bacterium, were engineered previously for increased
thermostability, either by SCHEMA, a structure-guided, site-directed protein
recombination method, or by consensus-guided mutagenesis combined with random
mutagenesis using error-prone PCR, respectively. A thermostable beta-glucosidase
BglA mutant was also selected from a library generated by error-prone PCR that
will assist the two cellulases in their methodic deconstruction of crystalline
cellulose. The effects of a thermostable scaffoldin versus those of a largely
mesophilic scaffoldin were also examined. By improving the stability of the
enzyme subunits and the structural component, we aimed to improve cellulosome
mediated deconstruction of cellulosic substrates. RESULTS: The results
demonstrate that the combination of thermostable enzymes as free enzymes and a
thermostable scaffoldin was more active on the cellulosic substrate than the wild
type enzymes. Significantly, "thermostable" designer cellulosomes exhibited a 1.7
fold enhancement in cellulose degradation compared to the action of conventional
designer cellulosomes that contain the respective wild-type enzymes. For designer
cellulosome formats, the use of the thermostabilized scaffoldin proved critical
for enhanced enzymatic performance under conditions of high temperatures.
CONCLUSIONS: Simple improvement in the activity of a given enzyme does not
guarantee its suitability for use in an enzyme cocktail or as a designer
cellulosome component. The true merit of improvement resides in its ultimate
contribution to synergistic action, which can only be determined experimentally.
The relevance of the mutated thermostable enzymes employed in this study as
components in multienzyme systems has thus been confirmed using designer
cellulosome technology. Enzyme integration via a thermostable scaffoldin is
critical to the ultimate stability of the complex at higher temperatures.
Engineering of thermostable cellulases and additional lignocellulosic enzymes may
prove a determinant parameter for development of state-of-the-art designer
cellulosomes for their employment in the conversion of cellulosic biomass to
soluble sugars.Graphical abstractConversion of conventional designer cellulosomes
into thermophilic designer cellulosomes.
PMID- 27493687
TI - Dynamic flux balance modeling to increase the production of high-value compounds
in green microalgae.
AB - BACKGROUND: Photosynthetic organisms can be used for renewable and sustainable
production of fuels and high-value compounds from natural resources. Costs for
design and operation of large-scale algae cultivation systems can be reduced if
data from laboratory scale cultivations are combined with detailed mathematical
models to evaluate and optimize the process. RESULTS: In this work we present a
flexible modeling formulation for accumulation of high-value storage molecules in
microalgae that provides quantitative predictions under various light and
nutrient conditions. The modeling approach is based on dynamic flux balance
analysis (DFBA) and includes regulatory models to predict the accumulation of
pigment molecules. The accuracy of the model predictions is validated through
independent experimental data followed by a subsequent model-based fed-batch
optimization. In our experimentally validated fed-batch optimization study we
increase biomass and [Formula: see text]-carotene density by factors of about 2.5
and 2.1, respectively. CONCLUSIONS: The analysis shows that a model-based
approach can be used to develop and significantly improve biotechnological
processes for biofuels and pigments.
PMID- 27493688
TI - Erratum to: Cost-effectiveness of clostridial collagenase ointment on wound
closure in patients with diabetic foot ulcers: economic analysis of results from
a multicenter, randomized, open-label trial.
AB - [This corrects the article DOI: 10.1186/s13047-015-0065-x.].
PMID- 27493690
TI - Intravenous zoledronate for osteoporosis: less might be more.
AB - Annual administration of 5 mg intravenous zoledronate is moderately effective in
reducing fracture risk in older adults, decreasing the relative risk of clinical
fracture by 33%. However, almost 10 years after its approval for use in clinical
practice there remain very substantial uncertainties about the optimal treatment
regimen, that is, the lowest dose and/or longest dosing interval that is
efficacious. Several pieces of clinical research suggest that the current
recommendation for annual administration of 5 mg zoledronate might represent
overtreatment. Clinical trials to clarify the optimal use of zoledronate for
reduction of fracture risk should be undertaken.
PMID- 27493689
TI - Remission-induction therapies for early rheumatoid arthritis: evidence to date
and clinical implications.
AB - Recent guidelines on rheumatoid arthritis (RA) point to the importance of
achieving remission as soon as possible during the course of the disease. The
appropriate use of antirheumatic drugs is critical, particularly in early RA
patients, before 24 weeks, since this is a 'window of opportunity' for treatment
to modify disease progression. A treat-to-target strategy added to an aggressive
therapeutic approach increases the chance of early remission, particularly in
early RA patients. We conducted an overview of current therapeutic strategies
leading to remission in early RA patients. We also provide interesting predictive
factors that can guide the RA management strategy with regard to disease
modifying treatment and/or drug-free remission.
PMID- 27493692
TI - Selected aspects of the current management of myositis.
AB - The idiopathic inflammatory myopathies (IIM) are a rare and heterogeneous group
of acquired autoimmune muscle disorders, often referred to as 'myositis'.
Clinical assessment, together with muscle biopsy findings and autoantibody status
are key factors to consider when making a diagnosis of IIM, and in stratification
of the 'IIM spectrum' into disease subgroups. Treatment stratified according to
serotype (and in the future, likely also genotype) is increasingly being used to
take account of the heterogeneity within the IIM spectrum. Subgroup
classification is also important in terms of monitoring for complications, such
as malignancy and interstitial lung disease. Disease monitoring should include
the use of standardized tools such as the IMACS disease activity outcome
measures. Other tools such as muscle MRI can be useful in identifying areas of
active muscle inflammation. Treatment outcomes in IIM remain unsatisfactory. The
evidence base to guide treatment decisions is remarkably limited. In addition to
muscle inflammation, a number of noninflammatory cell-mediated mechanisms may
contribute to weakness and disability, and for which no specific treatments are
currently available.
PMID- 27493691
TI - Maternal vitamin D levels during pregnancy and neonatal health: evidence to date
and clinical implications.
AB - Low maternal vitamin D levels during pregnancy have been associated with a
plethora of adverse neonatal outcomes, including small for gestational age and
preterm births, detrimental effect on offspring bone and teeth development, and
risk of infectious diseases. Although most observational studies indicate a
significant linear relationship between maternal 25-hydroxyvitamin D and the
above outcomes, some randomized controlled trials to date are inconclusive,
mostly due to differences in study design and supplementation regimen. The
currently available results indicate that vitamin D supplementation during
pregnancy reduces the risk of preterm birth, low birth weight, dental caries of
infancy, and neonatal infectious diseases such as respiratory infections and
sepsis. This narrative review aims to summarize available trial results regarding
the effect of low maternal vitamin D levels during pregnancy, in conjunction with
neonatal outcomes on the field, with a discourse on the appropriate clinical
approach of this important issue.
PMID- 27493693
TI - Treatment of hyperuricemia in gout: current therapeutic options, latest
developments and clinical implications.
AB - Despite being the most common type of inflammatory arthritis, gout is often
poorly managed. Except for febuxostat and pegloticase, research in new
therapeutic agents for the management of hyperuricemia in gout remained
insufficient for several decades. With emerging evidence of possible roles of
hyperuricemia in cardiometabolic comorbidities, as well as more convincing
evidence regarding poor outcomes (e.g. disability, recurrent hospital admissions)
in patients with uncontrolled gout, several agents are current under development.
Increasing knowledge regarding renal urate transporters has resulted in the
development of new generation uricosurics such as lesinurad and arhalofenate.
This review aims at discussing current therapeutic strategies for gout, as well
as their limitations and the possible role of emerging agents in the chronic
management of hyperuricemia in gout. Drugs in phases I and II of development will
be discussed, along with new agents and therapeutic classes, such as purine
nucleoside phosphorylase inhibitors and dual-action drugs. These new developments
are encouraging, and will hopefully contribute to a more adequate management of
hyperuricemia in gout.
PMID- 27493694
TI - Mobile and Wearable Device Features that Matter in Promoting Physical Activity.
AB - BACKGROUND: As wearable sensors/devices become increasingly popular to promote
physical activity (PA), research is needed to examine how and which components of
these devices people use to increase their PA levels. AIMS: (1) To assess
usability and level of engagement with the Fitbit One and daily SMS-based prompts
in a 6-week PA intervention, and (2) to examine whether use/ level of engagement
with specific intervention components were associated with PA change. METHODS:
Data were analyzed from a randomized controlled trial that compared (1) a
wearable sensor/ device (Fitbit One) plus SMS-based PA prompts, and (2) Fitbit
One only, among overweight/ obese adults (N = 67). We calculated average scores
from Likert-type response items that assessed usability and level of engagement
with device features (e.g., tracker, website, mobile app, and SMS-based prompts),
and assessed whether such factors were associated with change in steps/day (using
Actigraph GT3X+). RESULTS: Participants reported the Fitbit One was easy to use
and the tracker helped to be more active. Those who used the Fitbit mobile app
(36%) vs. those who did not (64%) had an increase in steps at 6-week follow-up,
even after adjusting for previous web/app use: +545 steps/ day (SE = 265) vs. -28
steps/ day (SE = 242) (p = .04). CONCLUSIONS: Level of engagement with the Fitbit
One, particularly the mobile app, was associated with increased steps. Mobile
apps can instantly display summaries of PA performance and could optimize self
regulation to activate change. More research is needed to determine whether such
modalities might be cost-effective in future intervention research and practice.
PMID- 27493695
TI - Homology modeling and virtual screening studies of FGF-7 protein-a structure
based approach to design new molecules against tumor angiogenesis.
AB - Keratinocyte growth factor (KGF) protein is a member of the fibroblast growth
factor (FGF) family, which is also known as FGF-7. The FGF-7 plays an important
role in tumor angiogenesis. In the present work, FGF-7 is treated as a potential
therapeutic target to prevent angiogenesis in cancerous tissue. Computational
techniques are applied to evaluate and validate the 3D structure of FGF-7
protein. The active site region of the FGF-7 protein is identified based on
hydrophobicity calculations using CASTp and Q-site Finder active site prediction
tools. The protein-protein docking study of FGF-7 with its natural receptor
FGFR2b is carried out to confirm the active site region in FGF-7. The amino acid
residues Asp34, Arg67, Glu116, and Thr194 in FGF-7 interact with the receptor
protein (FGFR2b). A grid is generated at the active site region of FGF-7 using
Glide module of Schrodinger suite. Subsequently, a virtual screening study is
carried out at the active site using small molecular structural databases to
identify the ligand molecules. The binding interactions of the ligand molecules,
with piperazine moiety as a pharmacophore, are observed at Arg67 and Glu149
residues of the FGF-7 protein. The identified ligand molecules against the FGF-7
protein show permissible pharmacokinetic properties (ADME). The ligand molecules
with good docking scores and satisfactory pharmacokinetic properties are
prioritized and identified as novel ligands for the FGF-7 protein in cancer
therapy.
PMID- 27493697
TI - JOCB Bulletin.
PMID- 27493696
TI - Synthesis of a series of novel 2,5-disubstituted-1,3,4-oxadiazole derivatives as
potential antioxidant and antibacterial agents.
AB - A series of novel 2,5-disubstituted-1,3,4-oxadiazole derivatives were synthesized
and screened for their antimicrobial and antioxidant activities. The assay
indicated that compounds 3c, 3d, and 3i exhibited comparable antibacterial and
antioxidant activity with first-line drugs. The structure activity relationship
and molecular docking study of the synthesized compounds are also reported.
PMID- 27493698
TI - Erratum to: Neural correlates of reward processing in adults with 22q11 deletion
syndrome.
AB - [This corrects the article DOI: 10.1186/s11689-016-9158-5.].
PMID- 27493699
TI - Tobacco smoking differently influences cell types of the innate and adaptive
immune system-indications from CpG site methylation.
AB - BACKGROUND: Tobacco smoke is worldwide one of the main preventable lifestyle
inhalative pollutants causing severe adverse health effects. Epidemiological
studies revealed association of tobacco smoking with epigenetic changes at single
CpGs in blood. However, the biological relevance of the often only marginal
methylation changes remains unclear. RESULTS: Comparing genome-wide changes in
CpG methylation of three recently reported epidemiological datasets, two obtained
on whole blood and one on peripheral blood mononuclear cells (PBMCs), it becomes
evident that the majority of methylation changes (86.7 and 93.3 %) in whole blood
account for changes in granulocytes. Analyzing, in more detail, seven highly
significant reported smoking-induced methylation changes at single CpGs in
different blood cell types of healthy volunteers (n = 32), we confirmatively
found a strong cell-type specificity. Two CpGs in GFI1 and F2RL3 were
significantly hypomethylated in granulocytes (-11.3 %, p = 0.001; -8.7 %, p =
0.001, respectively) but not in PBMCs of smokers while two CpGs in CPOX and GPR15
were found to be hypomethylated in PBMC (-4.3 %, p = 0.003; -4.2 %, P = 0.009,
respectively) and their subtypes of GPR15 non-expressing (-3.2 %, p = 0.027; -2.5
%, p = 0.032, respectively) and smoking-evoked GPR15 expressing T cells (-15.8 %,
p < 0.001; -13.8 %, p = 0.018, respectively) but not in granulocytes. In
contrast, cg05575921 within AHRR was hypomethylated in every analyzed cell type
of smokers, but with a different degree. Both, hypomethylation at cg05575921 in
granulocytes (-55.2 % methylation change in smokers, p < 0.001) and the frequency
of GPR15+ T cells (9.8-37.1 % in smokers), possessing a specific hypomethylation
at cg19859270, were strongly associated with smoking behavior at individual level
and could therefore serve as valuable biomarkers indicating a disturbed
homeostasis in smokers. In contrast to the reported long-term persistent
methylation changes in adult smokers after cessation, the hypomethylation at
cg05575921 in prenatally tobacco smoke-exposed children (n = 13) from our LINA
cohort was less stable and disappeared already within 2 years after birth.
CONCLUSIONS: Studying cell type-specific methylation changes provides helpful
information regarding the biological relevance of epigenetic modifications. Here,
we could show that smoking differently affects both cells of the innate and
adaptive immune systems.
PMID- 27493700
TI - Erratum to: MSRE-HTPrimer: a high-throughput and genome-wide primer design
pipeline optimized for epigenetic research.
AB - [This corrects the article DOI: 10.1186/s13148-016-0190-9.].
PMID- 27493702
TI - Fabrication of anti-protein-fouling poly(ethylene glycol) microfluidic chip
electrophoresis by sandwich photolithography.
AB - Microfluidic chip electrophoresis (MCE) is a powerful separation tool for
biomacromolecule analysis. However, adsorption of biomacromolecules, particularly
proteins onto microfluidic channels severely degrades the separation performance
of MCE. In this paper, an anti-protein-fouling MCE was fabricated using a novel
sandwich photolithography of poly(ethylene glycol) (PEG) prepolymers.
Photopatterned microchannel with a minimum resolution of 10 MUm was achieved.
After equipped with a conventional online electrochemical detector, the device
enabled baseline separation of bovine serum albumin, lysozyme (Lys), and
cytochrome c (Cyt-c) in 53 s under a voltage of 200 V. Compared with a
traditional polydimethylsiloxane MCE made by soft lithography, the PEG MCE made
by the sandwich photolithography not only eliminated the need of a master mold
and the additional modification process of the microchannel but also showed
excellent anti-protein-fouling properties for protein separation.
PMID- 27493701
TI - Flow of DNA in micro/nanofluidics: From fundamentals to applications.
AB - Thanks to direct observation and manipulation of DNA in micro/nanofluidic
devices, we are now able to elucidate the relationship between the polymer
microstructure and its rheological properties, as well as to design new single
molecule platforms for biophysics and biomedicine. This allows exploration of
many new mechanisms and phenomena, which were previously unachievable with
conventional methods such as bulk rheometry tests. For instance, the field of
polymer rheology is at a turning point to relate the complex molecular
conformations to the nonlinear viscoelasticity of polymeric fluids (such as coil
stretch transition, shear thinning, and stress overshoot in startup shear). In
addition, nanofluidic devices provided a starting point for manipulating single
DNA molecules by applying basic principles of polymer physics, which is highly
relevant to numerous processes in biosciences. In this article, we review recent
progress regarding the flow and deformation of DNA in micro/nanofluidic systems
from both fundamental and application perspectives. We particularly focus on
advances in the understanding of polymer rheology and identify the emerging
research trends and challenges, especially with respect to future applications of
nanofluidics in the biomedical field.
PMID- 27493703
TI - On-chip clearing of arrays of 3-D cell cultures and micro-tissues.
AB - Three-dimensional (3-D) cell cultures are beneficial models for mimicking the
complexities of in vivo tissues, especially in tumour studies where transport
limitations can complicate response to cancer drugs. 3-D optical microscopy
techniques are less involved than traditional embedding and sectioning, but are
impeded by optical scattering properties of the tissues. Confocal and even two
photon microscopy limit sample imaging to approximately 100-200 MUm depth, which
is insufficient to image hypoxic spheroid cores. Optical clearing methods have
permitted high-depth imaging of tissues without physical sectioning, but they are
difficult to implement for smaller 3-D cultures due to sample loss in solution
exchange. In this work, we demonstrate a microfluidic platform for high
throughput on-chip optical clearing of breast cancer spheroids using the SeeDB,
Clear(T2), and ScaleSQ clearing methods. Although all three methods are able to
effectively clear the spheroids, we find that SeeDB and ScaleSQ more effectively
clear the sample than Clear(T2); however, SeeDB induces green autofluorescence
while ScaleS causes sample expansion. Our unique on-chip implementation permits
clearing arrays of 3-D cultures using perfusion while monitoring the 3-D cultures
throughout the process, enabling visualization of the clearing endpoint as well
as monitoring of transient changes that could induce image artefacts. Our
microfluidic device is compatible with on-chip 3-D cell culture, permitting the
use of on-chip clearing at the endpoint after monitoring the same spheroids
during their culture. This on-chip method has the potential to improve readout
from 3-D cultures, facilitating their use in cell-based assays for high-content
drug screening and other applications.
PMID- 27493704
TI - Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is
Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells.
AB - 2-DG triggers glucose deprivation without altering other nutrients or metabolic
pathways and then activates autophagy via activation of AMPK and endoplasmic
reticulum (ER) stress. We investigated whether 2-DG reduced intracellular insulin
increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and
GRP78/BiP level were significantly increased by 2-DG in the presence/absence of
melatonin, but IRE1alpha level was reduced in 2-DG treatment. Levels of p85alpha,
p110, p-Akt (Ser473, Thr308), and p-mTOR (Ser2481) were also significantly
reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG
plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was
decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with
2-DG treatment in the presence/absence of melatonin. Intracellular insulin
production increased in melatonin plus 2-DG but reduced in treatment with 2-DG
with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of
melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a
dose-dependent manner and subsequently resulted in a decrease in intracellular
production of insulin. These results suggest that melatonin-mediated insulin
synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat
insulinoma INS-1E cells and subsequently results in a decrease in intracellular
production of insulin.
PMID- 27493705
TI - Antioxidant and Antihyperlipidemic Effects of Campomanesia adamantium O. Berg
Root.
AB - Campomanesia adamantium O. Berg, popularly known as guavira, has been used in
Brazilian traditional medicine for reduction of serum lipid. The present study
was carried out to investigate the antioxidant and antihyperlipidemic effects of
Campomanesia adamantium root aqueous extract (ExCA). Phenolic compounds were
quantified in the ExCA and gallic and ellagic acids were identified by HPLC. ExCA
showed efficiency in 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, with
IC50 similar to butylhydroxytoluene control, and protected the erythrocytes
against lipid peroxidation induced by 2,2'-azobis(2-methylpropionamidine)
dihydrochloride, reducing generated malondialdehyde. Hyperlipidemic Wistar rats
treated daily by gavage during eight weeks with ExCA (200 mg/kg of body weight)
showed reduced serum level of total cholesterol and triglycerides, similar to
normolipidemic rats and hyperlipidemic rats treated with simvastatin (30 mg/kg of
body weight) and ciprofibrate (2 mg/kg of body weight). Moreover, the treatment
with ExCA also decreased malondialdehyde serum level in the hyperlipidemic rats.
The body weight and organ mass were unmodified by ExCA in hyperlipidemic rats,
except an increase of liver mass; however, the hepatic enzymes, alanine
aminotransferase and aspartate aminotransferase, were unchanged. Together, these
results confirm the potential value of Campomanesia adamantium root for lowering
lipid peroxidation and lipid serum level, improving risk factors for
cardiometabolic diseases development.
PMID- 27493707
TI - The combination of breast necrosis and chylothorax following the OPCAB.
AB - Due to long term patency, the internal mammary artery is considered as a conduit
of choice for revascularization of the left anterior descending coronary artery.
The internal mammary artery and its accessory branches in addition to perfusing
the chest wall structures also contributes to supplying, part of the female
breast arteries. In addition, due to the accompaniment of thoracic duct branches
with the left internal mammary artery, harvesting may be associated with injury
to these branches and contribute to chylothorax. We report a rare case of
chylothorax and the breast necrosis following the coronary artery bypass
grafting. The chylothorax was started in the second postoperative day and ceased
gradually in the 12th day of operation. The breast necrosis appeared in the 3th
weeks of operation with pain, and tenderness and black skin color change. The
patient underwent total mastectomy in the 4th weeks of operation.
PMID- 27493706
TI - Erythropoietin Restores Long-Term Neurocognitive Function Involving Mechanisms of
Neuronal Plasticity in a Model of Hyperoxia-Induced Preterm Brain Injury.
AB - Cerebral white and grey matter injury is the leading cause of an adverse
neurodevelopmental outcome in prematurely born infants. High oxygen
concentrations have been shown to contribute to the pathogenesis of neonatal
brain damage. Here, we focused on motor-cognitive outcome up to the adolescent
and adult age in an experimental model of preterm brain injury. In search of the
putative mechanisms of action we evaluated oligodendrocyte degeneration,
myelination, and modulation of synaptic plasticity-related molecules. A single
dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80%
oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development
up to the adolescent and adult stage. Analysis of white matter structures
revealed a reduction of acute oligodendrocyte degeneration. However,
erythropoietin did not influence hypomyelination occurring a few days after
injury or long-term microstructural white matter abnormalities detected in adult
animals. Erythropoietin administration reverted hyperoxia-induced reduction of
neuronal plasticity-related mRNA expression up to four months after injury. Thus,
our findings highlight the importance of erythropoietin as a neuroregenerative
treatment option in neonatal brain injury, leading to improved memory function in
adolescent and adult rats which may be linked to increased neuronal network
connectivity.
PMID- 27493708
TI - Ibrutinib in Waldenstrom macroglobulinemia: latest evidence and clinical
experience.
AB - Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor, which has recently
gained approval by the United States (US) Food and Drug Administration (FDA) and
the European Medicines Agency (EMA) for the treatment of patients with
symptomatic Waldenstrom macroglobulinemia (WM). Herein, we review the role of BTK
in the pathophysiology of WM, and present the results of the preclinical and
clinical studies that led to the initial investigation and later approval of
ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM
patients, especially focusing on genomic profiling and the impact on response to
ibrutinib, and the management of adverse events.
PMID- 27493709
TI - Elotuzumab: the first approved monoclonal antibody for multiple myeloma
treatment.
AB - Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor,
expressed on normal and malignant plasma cells with a lower expression on other
lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant
antimyeloma activity when given as a single agent to patients with relapsed or
refractory multiple myeloma (RRMM). However, when combined with other antimyeloma
agents, it results in improved response and outcome. Owing to the results from
the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and
dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in
combination with lenalidomide and dexamethasone was approved by the American Food
and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients
who received one to three prior lines of therapy. This review will give a brief
description of the signaling lymphocytic activation molecule (SLAM) family
receptors, the unique SLAMF7 receptor and the mechanism of action of elotuzumab.
Thereafter, we will give an overview on its antimyeloma activity in preclinical
and clinical trials, including its toxicity profile and management thereof.
PMID- 27493710
TI - Bortezomib for the treatment of mantle cell lymphoma: an update.
AB - Bortezomib is a first in class proteasome inhibitor, initially approved by the US
Food and Drug Administration for the treatment of plasma cell myeloma. Bortezomib
has been approved for the treatment of relapsed and refractory mantle cell
lymphoma (MCL) and, more recently, in the upfront setting as well. Treatment
algorithms for MCL have rapidly evolved over the past two decades, and the
optimal regimen remains to be defined. The choice of treatment regimen is based
on disease risk stratification models, the expected toxicity of antineoplastic
agents, the perceived patient ability to tolerate the planned treatments and the
availability of novel agents. As new drugs with novel mechanisms of action and
variable toxicity profiles come into use, treatment decisions for a given patient
have become increasingly complex. This article provides an overview of the
evolving use of bortezomib in the rapidly changing management landscape of MCL.
PMID- 27493711
TI - A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma.
AB - Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration
(FDA) approved for the treatment of multiple myeloma, 5q- myelodysplasia and
mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell
malignancies. Its unique mechanism of action is in part due to altering the tumor
microenvironment and potentiating the activity of T and natural-killer (NK)
cells. Impressive clinical activity and excellent tolerability allows broad
applicability. Lenalidomide has been used in a wide range of B-cell malignancies
for years, but in 2013, the FDA marked its approval as a single agent only in
relapsed/refractory mantle-cell lymphoma. Perhaps most impressive is the efficacy
of lenalidomide when combined with monoclonal antibodies. Impressive efficacy and
toxicity profiles with the combination of lenalidomide and rituximab in B-cell
lymphomas in both the upfront and relapsed/refractory setting may allow a shift
in our current treatment paradigm in both indolent and aggressive non-Hodgkin
lymphoma (NHL). This review will summarize the current data in the
relapsed/refractory and front-line setting of NHL with single-agent lenalidomide
as well as its use in combination with other agents.
PMID- 27493712
TI - Ofatumumab plus chlorambucil as a first-line therapy in less fit patients with
chronic lymphocytic leukemia: analysis of COMPLEMENT1 and other monoclonal
antibodies association data.
AB - The management of patients with chronic lymphocytic leukemia (CLL) has radically
improved over the last few years with the addition of anti-CD20 monoclonal
antibodies (MoAbs) to chemotherapy. Chlorambucil has been considered for decades
as a suitable therapeutic option for frail patients. Taking into account the
advantage offered by the addition of MoAbs to chemotherapy, different studies up
to now have explored the feasibility of chlorambucil-based chemoimmunotherapies
in treatment-naive CLL. COMPLEMENT1 is a prospective, randomized, open-label
trial evaluating the efficacy and safety of ofatumumab added to chlorambucil,
compared with chlorambucil in monotherapy, in the setting of untreated patients
with CLL considered unsuitable for a fludarabine-based approach. Progression-free
survival was significantly longer in the chemoimmunotherapy arm when compared
with the single-agent chlorambucil (22.4 months versus 13.1 months). Response
rate and quality were also improved in the combination arm. Furthermore, the
addition of ofatumumab did not lead to an unmanageable toxicity. While the
employment of anti-CD20 antibodies represents an advantage in the treatment of
the CLL symptomatic population, at present different patient selection and
treatment schedules do not allow a reliable comparison between chlorambucil-based
regimens. The addition of ofatumumab to chlorambucil represents a further
therapeutic gain in CLL. Longer follow up and direct comparison with other MoAbs
are warranted to establish the preferred first-line treatment in elderly and
unfit patients.
PMID- 27493713
TI - Unusual, spontaneous aneurysm formation in a patient being treated with ibrutinib
for chronic lymphocytic leukemia.
PMID- 27493714
TI - Osteogenic differentiation of human mesenchymal stem cells promotes
mineralization within a biodegradable peptide hydrogel.
AB - An attractive strategy for the regeneration of tissues has been the use of
extracellular matrix analogous biomaterials. Peptide-based fibrillar hydrogels
have been shown to mimic the structure of extracellular matrix offering cells a
niche to undertake their physiological functions. In this study, the capability
of an ionic-complementary peptide FEFEFKFK (F, E, and K are phenylalanine,
glutamic acid, and lysine, respectively) hydrogel to host human mesenchymal stem
cells in three dimensions and induce their osteogenic differentiation is
demonstrated. Assays showed sustained cell viability and proliferation throughout
the hydrogel over 12 days of culture and these human mesenchymal stem cells
differentiated into osteoblasts simply upon addition of osteogenic stimulation.
Differentiated osteoblasts synthesized key bone proteins, including collagen-1
(Col-1), osteocalcin, and alkaline phosphatase. Moreover, mineralization occurred
within the hydrogel. The peptide hydrogel is a naturally biodegradable material
as shown by oscillatory rheology and reversed-phase high-performance liquid
chromatography, where both viscoelastic properties and the degradation of the
hydrogel were monitored over time, respectively. These findings demonstrate that
a biodegradable octapeptide hydrogel can host and induce the differentiation of
stem cells and has the potential for the regeneration of hard tissues such as
alveolar bone.
PMID- 27493716
TI - Multipotent adult progenitor cells on an allograft scaffold facilitate the bone
repair process.
AB - Multipotent adult progenitor cells are a recently described population of stem
cells derived from the bone marrow stroma. Research has demonstrated the
potential of multipotent adult progenitor cells for treating ischemic injury and
cardiovascular repair; however, understanding of multipotent adult progenitor
cells in orthopedic applications remains limited. In this study, we evaluate the
osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in
vitro and loaded onto demineralized bone matrix in vivo, with comparison to
mesenchymal stem cells, as the current standard. When compared to mesenchymal
stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic
protein release profile in vitro and developed more extensive vasculature within
2 weeks in vivo. The establishment of this vascular network is critical to the
ossification process, as it allows nutrient exchange and provides an influx of
osteoprogenitor cells to the wound site. In vitro assays confirmed the
multipotency of multipotent adult progenitor cells along mesodermal lineages and
demonstrated the enhanced expression of alkaline phosphatase and production of
calcium-containing mineral deposits by multipotent adult progenitor cells,
necessary precursors for osteogenesis. In combination with a demineralized bone
matrix scaffold, multipotent adult progenitor cells demonstrated enhanced
revascularization and new bone formation in vivo in an orthotopic defect model
when compared to mesenchymal stem cells on demineralized bone matrix or
demineralized bone matrix-only control groups. The potent combination of
angiogenic and osteogenic properties provided by multipotent adult progenitor
cells appears to create a synergistic amplification of the bone healing process.
Our results indicate that multipotent adult progenitor cells have the potential
to better promote tissue regeneration and healing and to be a functional cell
source for use in orthopedic applications.
PMID- 27493715
TI - Methods for culturing retinal pigment epithelial cells: a review of current
protocols and future recommendations.
AB - The retinal pigment epithelium is an important part of the vertebrate eye,
particularly in studying the causes and possible treatment of age-related macular
degeneration. The retinal pigment epithelium is difficult to access in vivo due
to its location at the back of the eye, making experimentation with age-related
macular degeneration treatments problematic. An alternative to in vivo
experimentation is cultivating the retinal pigment epithelium in vitro, a
practice that has been going on since the 1970s, providing a wide range of
retinal pigment epithelial culture protocols, each producing cells and tissue of
varying degrees of similarity to natural retinal pigment epithelium. The purpose
of this review is to provide researchers with a ready list of retinal pigment
epithelial protocols, their effects on cultured tissue, and their specific
possible applications. Protocols using human and animal retinal pigment
epithelium cells, derived from tissue or cell lines, are discussed, and
recommendations for future researchers included.
PMID- 27493717
TI - Differential protection of black-seed oil on econucleotidase, cholinesterases and
aminergic catabolizing enzyme in haloperidol-induced neuronal damage of male
rats.
AB - BACKGROUND: The antipsychotic, haloperidol, is extremely efficient in the
treatment of schizophrenia but its application is constrained because of
irreversible adverse drug reactions. Hence, in this study, we investigate the
differential effects of black seed oil on cholinesterase [acetylcholinesterase
(AChE) and butrylcholinesterase (BuChE), ectonucleotidase (5'-nucleotidase),
lactate dehydrogenase (LDH) and monoamine oxidase (MAO)] activities and relevant
markers of oxidative stress in the cerebrum of haloperidol-induced neuronal
damaged rats. METHODS: The animals were divided into six groups (n = 10): normal
control rats; haloperidol-induced rats: induced rats were pre-, co- and post
treated with black-seed oil respectively, while the last group was treated with
extract oil only. The treatment was performed via oral administration and the
experiment lasted 14 days. RESULTS: The results revealed an increase in 5(I)
nucleotidase, a marker of adenosine triphosphate (ATP) and adenosine
monophosphate (AMP) hydrolysis, as well as AChE, BuChE and MAO activities, with
concomitant decrease in LDH activity of cerebrum in induced rats when compared
with controls. Also, administration of haloperidol caused systemic oxidative
damage and adverse histopathological changes in neuronal cells, indications of
mental disorder. The differential treatments with black-seed oil prevented these
alterations by increasing LDH and decreasing 5(I) nucleotidase, AChE, BuChE and
MAO activities in the cerebrum. Essential oil post-treatment is most efficacious
in reversing haloperidol-induced neuronal damage in rat; followed by pre- and
cotreatment, respectively. CONCLUSIONS: We concluded that essential black-seed
oil enhanced the wellness of aminergic, purinergic and cholinergic
neurotransmissions of haloperidol-induced neuronal damage in rats.
PMID- 27493719
TI - Making rational choices about how best to support consumers' use of medicines: a
perspective review.
AB - Inappropriate medicine use and polypharmacy create significant challenges for
consumers and the health systems they live in, worldwide. In this review, we
describe the evidence underpinning interventions directed primarily at healthcare
consumers, including information provision, pharmacist-delivered interventions
and practical supports, such as reminders to improve outcomes related to
medicines. We identify a relatively small number of strategies that seem
effective or promising: self-monitoring and self-management programmes,
simplified dosing regimens and pharmacist-delivered interventions such as
medication review. These interventions could be applied in practice to address
some of the problems associated with inappropriate use of medicines,
multimorbidity and polypharmacy. The evidence also indicates that success with
many strategies is not consistent, suggesting that understanding the individual's
context and their preferences will also be important for improving medicines'
use. In addition, some strategies in current use are ineffective. Taken together,
we argue that the evidence should inform deliberate, rational decisions between
strategies to support consumers in using medicines safely and effectively. Future
medicine-use research should likewise build rationally and constructively on what
is known about promising interventions, avoiding duplication of past research,
and working to help consumers negotiate the many challenges presented by
polypharmacy.
PMID- 27493718
TI - Medication-overuse headache: a perspective review.
AB - Medication-overuse headache (MOH) is a debilitating condition in which frequent
and prolonged use of medication for the acute treatment of pain results in the
worsening of the headache. The purpose of this paper is to review the most recent
literature on MOH and discuss future avenues for research. MOH accounts for a
substantial share of the global burden of disease. Prevalence is often reported
as 1-2% but can be as high as 7% overall, with higher proportions among women and
in those with a low socioeconomic position. Management consists of withdrawing
pain medication, focusing on prophylactic and nonmedical treatments, and limiting
acute symptomatic medication. Stress reduction and lifestyle interventions may
support the change towards rational pain medication use. Support, follow up, and
education are needed to help patients through the detoxification period. There is
fertile ground for research in MOH epidemiology, pathophysiology, and
neuroimaging. Randomized and long-term follow-up studies on MOH treatment
protocols are needed. Further focused research could be of major importance for
global health.
PMID- 27493720
TI - Nonmedical prescribing: where are we now?
AB - Nonmedical prescribing has been allowed in the United Kingdom (UK) since 1992.
Its development over the past 24 years has been marked by changes in legislation,
enabling the progression towards independent prescribing for nurses, pharmacists
and a range of allied health professionals. Although the UK has led the way
regarding the introduction of nonmedical prescribing, it is now seen in a number
of other Western-European and Anglophone countries although the models of
application vary widely between countries. The programme of study to become a
nonmedical prescriber (NMP) within the UK is rigorous, and involves a combination
of taught curricula and practice-based learning. Prescribing is a complex skill
that is high risk and error prone, with many influencing factors. Literature
reports regarding the impact of nonmedical prescribing are sparse, with the
majority of prescribing research tending to focus instead on prescribing by
doctors. The impact of nonmedical prescribing however is important to evaluate,
and can be carried out from several perspectives. This review takes a brief look
back at the history of nonmedical prescribing, and compares this with the
international situation. It also describes the processes required to qualify as a
NMP in the UK, potential influences on nonmedical prescribing and the impact of
nonmedical prescribing on patient opinions and outcomes and the opinions of
doctors and other healthcare professionals.
PMID- 27408687
TI - Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation
p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis
bullosa.
AB - Dystrophic epidermolysis bullosa simplex (DEB) is a phenotypically diverse
inherited skin fragility disorder. It is majorly manifested by appearance of
epidermal bullae upon friction caused either by physical or environmental trauma.
The phenotypic manifestations also include appearance of milia, scarring all over
the body and nail dystrophy. DEB can be inherited in a recessive or dominant form
and the recessive form of DEB (RDEB) is more severe. In the present study, we
identify a novel p.G2254fs mutation in COL7A1 gene causing a sporadic case of
RDEB by whole exome sequencing (WES). Apart from adding a novel frameshift
Collagen VII mutation to the repertoire of known mutations reported in the
disease, to the best of our knowledge, this is the first report of a genetically
characterized case of DEB from India.
PMID- 27493721
TI - Different risk factor patterns for adult asthma, rhinitis and eczema: results
from West Sweden Asthma Study.
AB - BACKGROUND: Atopic diseases including asthma, rhinitis and eczema have increased
in the second half of the past century. This has been well studied among children
and adolescents but with the exception of asthma to a much lesser extent in
adults. The adult risk factor pattern of atopic diseases, in particular of
eczema, and their relation to allergic sensitization are yet to be fully
elucidated. Studies among adults that have compared the risk factor pattern for
these conditions in the same material are very few. The objective of this study
was to compare the risk factor patterns for asthma, rhinitis and eczema in a
randomly selected adult population. METHODS: A questionnaire survey on atopic
diseases was dispatched by mail to 30,000 randomly selected individuals in West
Sweden aged 16-75 years and 62 % participated. A subgroup of 2000 individuals was
selected for clinical examinations including blood sampling for specific serum
Immunoglobulin E to common airborne allergens and 1172 attended. RESULTS: The
prevalence of current asthma was 11.8 %, current rhinitis 42.8 %, current eczema
13.5 and 2.3 % had all three conditions while 13.9 % had at least two conditions.
No mutual risk factor was identified for all three conditions. Allergic
sensitization was a strong risk factor for current asthma (OR 4.1 CI 2.7-6.3) and
current rhinitis (OR 5.1 CI 3.8-6.9) but not so for current eczema. Obesity was a
risk factor for current asthma and current rhinitis, while farm childhood
decreased the risk for current asthma and current rhinitis. Occupational exposure
to gas dust or fumes and female sex was associated with an increased risk of
current asthma and current eczema. CONCLUSIONS: There are different risk factor
patterns for asthma, rhinitis and eczema in adults but some risk factors are
overlapping between some of the conditions. The effect of mutable risk factors
should be assessed further in longitudinal studies.
PMID- 27347383
TI - Where are the female science professors? A personal perspective.
AB - The first woman to earn a Professorship at a University in Europe was Laura Maria
Caterina Bassi, who earned a professorship in physics at the University of
Bologna in 1732. Almost 300 years and three waves of feminism later, in 2016,
women typically still only comprise 20% (or less) of the number of full
professors in Europe. This opinion article will discuss the experiences of being
a female academic today and the factors contributing to the academic gender gap
from the perspective of a "young" natural scientist, as well as providing
constructive suggestions for strategies to empower women in the academic world.
PMID- 27493725
TI - Essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA
expression in bovine mammary epithelial cells.
AB - BACKGROUND: The objective of this study was to study how changing the ratio of
Lys to Thr, Lys to His, and Lys to Val affects the expression of lipogenic genes
and microRNA (miRNA) in bovine mammary epithelial cells. RESULTS: Triplicate
cultures with the respective "optimal" amino acid (AA) ratio (OPAA = Lys:Met
2.9:1; Thr:Phe 1.05:1; Lys:Thr 1.8:1; Lys:His 2.38:1; Lys:Val 1.23:1) plus
rapamycin (OPAARMC; positive control), OPAA, Lys:Thr 2.1:1 (LT2.1), Lys:Thr 1.3:1
(LT1.3), Lys:His 3.05:1 (LH3.0), or Lys:Val 1.62:1 (LV1.6) were incubated in
lactogenic medium for 12 h. The expression of 15 lipogenic genes and 7 miRNA were
evaluated. Responses to LT2.1, LT1.3, LH3.0, and LV1.6 relative to the control
(OPAARMC) included up-regulated expression of ACSS2, FABP3, ACACA, FASN, SCD,
LPIN1, INSIG1, SREBF1, PPARD, and NR1H3 (commonly known as LXR-alpha).
Furthermore, LV1.6 up-regulated expression of ACSL1, DGAT1, and RXRA and down
regulated PPARG expression. Although no effect of OPAA on expression of PPARG was
observed, compared with the control, OPAA up-regulated expression of the PPAR
targets ACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, and SREBF1. Compared with
the control, the expression of the anti-lipogenic MIR27AB was down-regulated by
OPAA, LT2.1, LT1.3 and LH3.0. In contrast, compared with the control, the
expression of the pro-lipogenic MIR21 was up-regulated by LT2.1, LT1.3, LH3.0,
and LV1.6. CONCLUSIONS: The observed up-regulation of lipogenic gene networks and
the changes in expression of key miRNA involved in the control of lipogenic
balance are indicative of a potentially important role of EAA ratios and mTOR
signaling in the regulation of milk fat synthesis.
PMID- 27493724
TI - The IN/OUT assay: a new tool to study ciliogenesis.
AB - BACKGROUND: Nearly all cells have a primary cilia on their surface, which
functions as a cellular antennae. Primary cilia assembly begins intracellularly
and eventually emerges extracellularly. However, current ciliogenesis assays,
which detect cilia length and number, do not monitor ciliary stages. METHODS: We
developed a new assay that detects antibody access to a fluorescently tagged
ciliary transmembrane protein, which revealed three ciliary states: classified as
'inside,' 'outside,' or 'partial' cilia. RESULTS: Strikingly, most cilia in RPE
cells only partially emerged and many others were long and intracellular, which
would be indistinguishable by conventional assays. Importantly, these states
switch with starvation-induced ciliogenesis and the cilia can emerge both on the
dorsal and ventral surface of the cell. Our assay further allows new molecular
and functional studies of the 'ciliary pocket,' a deep plasma membrane
invagination whose function is unclear. Molecularly, we show colocalization of
EHD1, Septin 9 and glutamylated tubulin with the ciliary pocket. CONCLUSIONS:
Together, the IN/OUT assay is not only a new tool for easy and quantifiable
visualization of different ciliary stages, but also allows molecular
characterization of intermediate ciliary states.
PMID- 27493726
TI - Use of near-infrared reflectance spectroscopy for the rapid determination of the
digestible energy and metabolizable energy content of corn fed to growing pigs.
AB - BACKGROUND: The ability of near-infrared reflectance spectroscopy (NIRS) to
determine the digestible energy (DE) and metabolizable energy (ME) content of
corn fed to growing pigs was tested. One hundred and seventeen corn samples,
comprising different planting regions and varieties were collected from all over
China in a three-year period. The samples were randomly split into a calibration
set (n = 88) and a validation set (n = 29). The actual and calculated DE and ME
content of the corn samples was determined by digestion-metabolism experiments
and the prediction equations of Noblet and Perez (J Anim Sci. 71:3389-98,1993).
The samples were then subjected to NIRS scanning and calibrations were performed
by the modified partial least square (MPLS) regression method based on 77
different spectral pre-treatments. The NIRS equations based on the actually
determined and calculated DE and ME were built separately and then validated
using validation samples. RESULTS: The NIRS equations obtained from actually
determined DE, the coefficient of determination for calibration (RSQcal), cross
validation (R(2) CV), and validation (RSQv) were 0.89, 0.87 and 0.86, and these
values for determined ME were 0.87, 0.86 and 0.86. For the NIRS equations built
from calculated DE, the RSQcal, R(2) CV, and RSQv values were 0.88, 0.85 and
0.84, and these values for calculated ME were 0.86, 0.84 and 0.82. Except for the
equation based on calculated ME (RPDv = 2.38, < 2.50), the other three equations
built from actually determined energy and calculated DE produced good prediction
performance (RPDv ranging from 2.53 to 2.69, > 2.50) when applied to validation
samples. CONCLUSION: These results indicate that NIRS can be used as a
quantitative method for the rapid determination of the available energy in corn
fed to growing pigs, and the NIRS equations based on the actually determined
energy produced better predictive performance than those built from calculated
energy values.
PMID- 27493727
TI - Malonate as a ROS product is associated with pyruvate carboxylase activity in
acute myeloid leukaemia cells.
AB - BACKGROUND: The role of anaplerotic nutrient entry into the Krebs cycle via
pyruvate carboxylase has been the subject of increased scrutiny and in particular
whether this is dysregulated in cancer. Here, we use a tracer-based NMR analysis
involving high-resolution (1)H-(13)C-HSQC spectra to assess site-specific label
incorporation into a range of metabolite pools, including malate, aspartate and
glutamate in the acute myeloid leukaemia cell line K562. We also determine how
this is affected following treatment with the redeployed drug combination of the
lipid-regulating drug bezafibrate and medroxyprogesterone (BaP). RESULTS: Using
the tracer-based approach, we assessed the contribution of pyruvate carboxylase
(PC) vs. pyruvate dehydrogenase (PDH) activity in the derivation of Krebs cycle
intermediates. Our data show that PC activity is indeed high in K562 cells. We
also demonstrate a branched entry to the Krebs cycle of K562 cells with one
branch running counterclockwise using PC-derived oxaloacetate and the other
clockwise from the PDH activity. Finally, we show that the PC activity of K562
cells exclusively fuels the ROS-induced decarboxylation of oxaloacetate to
malonate in response to BaP treatment; resulting in further Krebs cycle
disruption via depletion of oxaloacetate and malonate-mediated inhibition of
succinate dehydrogenase (SDH) resulting in a twofold reduction of fumarate.
CONCLUSIONS: This study extends the interest in the PC activity in solid cancers
to include leukaemias and further demonstrates the value of tracer-based NMR
approaches in generating a more accurate picture of the flow of carbons and
metabolites within the increasingly inappropriately named Krebs cycle. Moreover,
our studies indicate that the PC activity in cancer cells can be exploited as an
Achilles heel by using treatments, such as BaP, that elevate ROS production.
PMID- 27493728
TI - Dial a Doctor: Improving lines of communication on the acute admissions unit.
AB - The Royal London Hospital operates a system of 'specialty take triage', meaning
that multiple teams provide patient care on the hospital's Acute Admission Unit
(AAU). The aim of this project is to ensure the medical team for each patient can
be promptly and easily contacted. An initial staff survey and engagement with key
stakeholders assessed the baseline situation and guided a series of
interventions, including the creation of ward whiteboards and funding for more
portable phones. During further improvement cycles representatives from each
profession were recruited to promote the new system, working groups held, and
presentations made at staff meetings. The staff survey was repeated to gauge
improvement. The initial survey of 33 staff revealed that there was no reliable
system for ascertaining the specialty team to which a patient had been allocated
or information on how to contact them. 39% of respondents reported experiencing a
situation they felt was unsafe. Following the initial interventions, 25 staff
responded to a second survey. 96% responded that the new system had made it
easier to contact the correct medical team. The percentage of staff reporting
difficulty knowing which medical team to contact most or everyday reduced from
66% to 32%. The percentage of those reporting difficulty contacting that team
most or everyday reduced from 36% to 12%. There were 22 respondents to the survey
following the second round of intervention. Less than 5% of staff reported
difficulty most or everyday in both identifying the correct medical team and
contacting them. There has been marked improvement in the ease of identifying and
contacting the medical teams. This project is ongoing, recognising that further
progress is required to ensure patient safety.
PMID- 27493729
TI - Reducing mortality from hip fractures: a systematic quality improvement
programme.
AB - Hip fracture is one of the most serious consequences of falls in the elderly,
with a mortality of 10% at one month and 30% at one year. Elderly patients with
hip fractures have complex medical, surgical, and rehabilitation needs, and a
well-coordinated multidisciplinary team approach is essential for the best
outcome. The model of best practice for hip fracture care is set out in the
Orthopaedic Blue Book and is incentivised by the best practice tariff. In 2009 to
2010, only 39.6% of our patients were being operated on within 36 hours, 19%
achieved best practice tariff [1], and mortality was 7.8%. We were ranked as one
of the worst hospitals to achieve best practice tariff [1] and our mortality was
average. The orthogeriatrics team at Ashford & St Peter's NHS Trust (SPH) was
implemented in 2010. Through a system redesign, regular governance meetings,
audits and quality improvement projects, we have managed to improve care for our
patients and reduce mortality. Over the last three years we have successfully
achieved best care for our hip fracture patients, demonstrating a steady
improvement in our attainment of the best practice tariff and a reduction in
mortality to 5.3% in 2013, which ranks us amongst the best trusts nationally.
PMID- 27493730
TI - Improving medical induction in obstetrics and gynaecology.
AB - We present a year long quality improvement project to bring a new induction
programme to the obstetrics and gynaecology (O&G) department of University
Hospital Lewisham (UHL). Aimed at non-speciality junior doctors, including
general practice and foundation trainees, the induction programme has sought to
improve the quality of care delivered and experience of these transiting junior
doctors. We have demonstrated a readily implementable and sustainable programme
that requires only modest input of time from senior trainees (ST3+) periodically
throughout the year. We have highlighted the specific need for senior consultant
investment in the success and sustainability of such a project. We have
demonstrated improvement of learning outcomes (p=0.01) in junior doctors
undertaking the induction programme at Kirkpatrick's hierarchy level 2.
PMID- 27493731
TI - Improving the quality of hospital discharge summaries utilising an electronic
prompting system.
AB - The discharge summary (DS) is a summary of an inpatient admission, patient's
health state, and future treatment plans which is delivered to the patient's
primary care provider. The DS is often incomplete, inaccurate, or unclear. The
aim of this project was to improve the quality of the DS through the use of an
electronic prompting system. The electronic prompting system was implemented in
the acute medical and surgical wards of the hospital as an adjunct to a pre
existing, widely used hospital program that documents all the patients in a ward
or belonging to a particular treating team. When using the program, a doctor
enters information (with the assistance of the treating consultant) from a drop
down menu and is prompted to include common, departmental specific diagnoses, co
morbidities, complications, and procedures that were commonly missed or
documented incorrectly in the DS. Fifteen DSs were randomly selected from a two
month period immediately prior to the intervention period and were rated by an
external, experienced general practitioner (GP) using a scoring system consistent
with the Australian Medical Association Guidelines for quality DSs. Fifteen
random DSs from a two month period, four months post-implementation were also
rated by the same GP. The quality of the DS improved in all categories evaluated.
The overall quality improved from mean (+/- SD) 2.86 +/- 1.64 to 4.13 +/- 0.92
out of 5 (p = 0.031). Additionally the implementation of the system was
associated with improvements in documentation of the diagnosis, co-morbidities
and other relevant clinical information. In summary, electronic prompting systems
can improve the quality of DSs to ensure the information contained within the DS
is more accurate and complete.
PMID- 27493732
TI - Recovery coaching in an acute older people rehabiliation ward.
AB - Our patient, carer, and staff feedback clearly tells us that elderly patients are
frequently disempowered by acute care provision, environments, and attitudes.
This debilitates individuals mentally and physically, reducing their independent
functioning, and may mean that they require prolonged care or are unfit to return
home. We developed the concept of "recovery coaching" to support acute inpatient
elderly care rehabilitation. We designed a training intervention to achieve
"coaching conversations" between our staff and our patients. Data were collected
from 46 participants; 22 in the pre-intervention stage and 24 in the post
intervention stage. For the post-intervention patients, mean scores indicated
that there was slightly higher increase in the patient's independence in terms of
their Barthel (ADL) scores and that they reported higher feelings of self
efficacy. For this patient group it was also found that more returned home with
the same level of care as on their admission, and that fewer patients required
residential care placements at discharge. This innovative intervention allowed us
to challenge the fundamental basis of "I do it for you" to "I will do it with
you", allowing the patient to become an integral partner in their health care.
PMID- 27493733
TI - Developing a Platform for Learning from Mistakes: changing the culture of patient
safety amongst junior doctors.
AB - Junior doctors commonly make mistakes which may compromise patient safety.
Despite the recent push by the NHS to encourage a "no blame" culture, mistakes
are still viewed as shameful, embarrassing and demoralising events. The current
model for learning from mistakes means that junior doctors only learn from their
own errors. A survey was designed by the author for all the Foundation Year 1
doctors (FY1s) at Yeovil District Hospital to understand better the culture
surrounding mistakes, and the types of mistakes that were being made. Using the
results of the survey and the support of senior staff, a "Near misses" session
has been introduced for FY1s once a month at which mistakes that have been made
are discussed, with a consultant present to facilitate the proceedings. The aims
of these sessions are to promote a culture of no blame, feedback information to
clinical governance, and share learning experiences. 100% of the FY1s had made a
mistake that could compromise patient safety. 63% discussed their mistakes with
colleagues, 44% with seniors, and only 13% with their educational supervisor.
Barriers to discussing mistakes included shame, embarrassment, fear of judgement,
and unapproachable seniors. 94% thought a "Near misses" session would be useful.
After the third session 100% of the FY1s agreed that the sessions were useful;
53% had changed their practice as a result of something they learned at the
sessions. After discussing errors as a group we have worked with the clinical
governance department, enacting strategies to avoid repetition of mistakes.
Feedback from the junior doctors has been overwhelmingly positive and we have
found these sessions to be a simple, inexpensive, and popular solution to
cultural change in our organisation.
PMID- 27493734
TI - Increasing uptake of bowel cancer screening.
AB - Uptake of bowel cancer screening uptake at our practice is 32.72%, which is below
the national target of 60%, but our cancer prevalence and death rate is higher
than our CCG statistical mean. We examined reasons for non-response to bowel
cancer screening in our patients and explored ways to promote engagement. From
August 2013 to February 2014 we used three interventions in two patient groups:
those turning 60 and eligible for screening (rising 60's) and non-responders to
screening. Interventions used were; letter encouragement for rising 60's, staff
education to increase opportunistic promotion of screening and calling non-
responders to identify reasons for non-participation and encourage participation.
Calls were made by either a Doctor or a Health Care Assistant (HCA); ethnicity,
language spoken, caller and call outcome was recorded. Rising 60's (n=26) had an
uptake of 46%, increased from 32.72%. From the non-responders (n = 73) we were
unable to contact 38%, 46% was due to an incorrect or no phone number. Of those
contacted main reasons for non-participation were not receiving a screening kit
(n=19) and not wanting to be screened (n=14). Following calls 66% of non
responders agreed to screening. From this 66% half (50%) completed screening with
a negative result. 15 non-responders refused screening following our calls, the
main reason given was not wanting to know if they had cancer (n =14). Calls from
doctor and HCA had similar rates of screening uptake (39% and 33% respectively).
Difficulty contacting patients was an unexpected barrier to screening and will be
addressed. Actively encouraging screening appears beneficial with similar
responses to Doctor and HCA. There appears to be a place for increased education
regarding screening and early detection of malignancy amongst patients. Overall
our interventions improved screening uptake at the practice and will be continued
in future.
PMID- 27493735
TI - Improving self-efficacy in spinal cord injury patients through "design thinking"
rehabilitation workshops.
AB - Advances in surgical and medical management have significantly reduced the length
of time that patients with spinal cord injury (SCI) have to stay in hospital, but
has left patients with potentially less time to psychologically adjust. Following
a pilot in 2012, this project was designed to test the effect of "design
thinking" workshops on the self-efficacy of people undergoing rehabilitation
following spinal injuries. Design thinking is about understanding the approaches
and methods that designers use and then applying these to think creatively about
problems and suggest ways to solve them. In this instance, design thinking is not
about designing new products (although the approaches can be used to do this) but
about developing a long term creative and explorative mind-set through skills
such as lateral thinking, prototyping and verbal and visual communication. The
principles of "design thinking" have underpinned design education and practice
for many years, it is also recognised in business and innovation for example, but
a literature review indicated that there was no evidence of it being used in
rehabilitation or spinal injury settings. Twenty participants took part in the
study; 13 (65%) were male and the average age was 37 years (range 16 to 72).
Statistically significant improvements were seen for EQ-5D score (t = -3.13, p =
0.007) and Patient Activation Measure score (t = -3.85, p = 0.001). Other outcome
measures improved but not statistically. There were no statistical effects on
length of stay or readmission rates, but qualitative interviews indicated
improved patient experience.
PMID- 27493736
TI - Improving pre-operative medicines reconciliation.
AB - An audit of 143 surgical admissions showed that only 30% of general surgery and
urology patients have complete medication charts on the day of surgery prior to
going to theatre, compared to 94% of orthopaedic patients. This was despite
having been seen previously in the pre-operative assessment clinic (POAC). These
patients went to the wards post-operatively, where many then missed doses of
their life-sustaining medications. Orthopaedic patients see a prescribing
pharmacist in POAC who undertakes medicines reconciliation; this is performed by
junior doctors for surgical patients. We designed three interventions to improve
drug chart completion by junior doctors, and gathered prospective data for 22
weeks in the POAC. We also recorded attendance of junior doctors in the POAC and
reasons for absence. Daily and weekly percentages of drug chart completion were
plotted on a run chart. The baseline completion rate was 43%. This rose to 45%
after the first and second interventions, and 51% after the third intervention.
However, the completion rate remained markedly below our target of 94%. Junior
doctors attended only 44% of POACs. They reported being "too busy to attend" 41%
of the time, and could not be contacted on 11% of occasions. Junior doctors
reported that they were unable to attend to both unwell inpatients and the POAC,
the latter seeming less of a priority. This was despite a rota allocating doctors
to attend POAC sessions free from clinical or teaching commitments. We were
unable to increase the rate of drug chart completion with the resources
available. We therefore recommend the employment of prescribing pharmacists in
the POAC for general surgery and urology patients.
PMID- 27493737
TI - Self-management of vaginal pessaries for pelvic organ prolapse.
AB - Two thirds of women opt to use a vaginal pessary initially to manage the symptoms
of pelvic organ prolapse. In the UK most women attend a health care professional
at least every six months to change the pessary. This represents a significant
burden both economically to the health care system and personally for the woman.
Annually there are more than 300 appointments for pessary changes at our
hospital. We developed a programme to teach women to self-manage their pessaries
with the aim of improving patient experience and reducing outpatient attendances
to free up outpatient capacity for new referrals. A physiotherapist was recuited
to deliver this programme involving a one to one training session supplemented
with written materials and an online video. Women using pessaries were offered
the option of self-management. Eighty-eight women aged between 29 to 84 years
enrolled in the programme. Sixty-three women (73% of those enrolled) successfully
continued with self-management at six months, creating 126 extra outpatient
appointment capacity in one year alone. Women self-managing reported higher
levels of convenience (94% vs 81%), accessibility (97% vs 73%), support (100% vs.
83%), and comfort (86% vs. 53%) than those attending the hospital for GP practice
for pessary change. Self-management appears to be an acceptable option for many
women using vaginal pessaries, with personal benefits to the women and economic
benefits to the hospital and commissioners.
PMID- 27493738
TI - Working better together: joint leadership development for doctors and managers.
AB - Traditionally, there have been tensions between frontline healthcare
professionals and managers, with well-known stereotypes of difficult consultants
and pen-pushing managers. Many junior doctors have limited management experience
and have often never even met a manager prior to taking on a consultant role.
Based on a successful programme pioneered by Dr Robert Klaber (Imperial, London)
we have set-up an innovative scheme for Birmingham Children's Hospital, pairing
junior doctors and managers to learn and work together. Our aim was to cultivate
positive attitudes and understanding between the two groups, break down inter
professional barriers, and to provide practical leadership experience and
education. We recruited 60 managers and doctors to participate in shadowing,
conversation, and quality improvement projects. Thought-provoking online
materials, blogs, socials, and popular monthly workshops consisting of patient
focused debate and discussion around key leadership themes, have helped to
support learning and cement shared values. Formal evaluation has demonstrated an
improvement in how participants perceive their knowledge and ability based on key
NHS Leadership Framework competencies. Participant feedback has been extremely
positive, and everyone plans to continue to incorporate Paired Learning into
their continuing professional development. We are now embedding Paired Learning
in the on-going educational programme offered at Birmingham Children's Hospital,
whilst looking at extending the scheme to include different professional groups
and other trusts across the region and nationally.
PMID- 27493740
TI - Improving junior doctor handover between jobs.
AB - Patient safety is one of the most important issues in healthcare. In recent years
there has been much focus on "Black Wednesday"; the day that Foundation doctors
start their first jobs. Great efforts have been made to ensure that patient
safety on this day has improved, with the main example being that newly qualified
doctors now use some of their free time between medical school and starting their
first job to shadow their outgoing counterparts. However, because Foundation
doctors start a brand new job approximately every four months for two years,
subsequent job changeovers were identified as a time of potential problems and
increased patient risk. It is not practical to shadow prior to every job because
junior doctors are needed in their current post right up until changeover day, so
a simple way to smooth this transition was needed. A handover lunch seemed to be
a feasible solution. The day before Foundation doctors change jobs, an hour is
dedicated for Foundation Year 1 doctors (F1's) to sit down together over lunch
(provided by the mess) and take a formal handover of all relevant information
about their forthcoming job and discuss current inpatients. Results showed that
100% of those surveyed mentioned face to face handover as essential, 93.75% said
it was either helpful or extremely helpful to have a dedicated time for F1's to
handover, and 12.5% said they would not have sought a face to face handover
otherwise. Apart from being extremely simple and cheap, it was very popular with
the F1's in the trust. It enables effective working from day one and is a great
team building activity.
PMID- 27493739
TI - Improving handover of patient care using a new weekend proforma with a focus on
ceiling of care.
AB - Patient handover is paramount for effective patient care and is often poorly
documented or incomplete. North Bristol NHS Trust weekend handover proformas
identify medical patients requiring weekend review. Many patients seen during on
call shifts are not handed over. Our aim was to develop Friday ward round
proforma sheets for medical patients, to encourage clear documentation of
management plans in order to improve handover of important information,
particularly ceiling of care decisions. Questionnaires were completed by F1
doctors regarding current handover systems. Baseline data collected by on-call
F1s included time of understanding a patient's ceiling of care decision, and
difficulty of comprehension of medical notes. Repeat data were collected with
novel proformas in situ. Multiple cycles were performed to refine the sheets and
target problems arising in their use. Ninety-three percent of F1s wanted improved
patient handover, with ceiling of care (87%) and management plans (73%) being the
most difficult areas to understand. Time taken to ascertain ceiling of care
decisions improved with the introduction of Friday handover proformas; mean time
153 seconds before and 5 seconds after. Clarity and documentation of management
plans improved, with 50% improvement in ease of understanding medical notes.
Results demonstrate that introducing Friday ward round proformas for medical
patients improves communication between weekday and on-call teams, highlights
current escalation of care plans, and leads to faster decision-making. Future
plans include the introduction of a short educational session to the new F1
doctors and continued progress with introduction into hospital stationary.
PMID- 27493741
TI - Reducing non-attendance rates in a community mental health team.
AB - The project aimed to improve productivity of psychiatric out patient clinic using
quality improvement techniques through "Listening Into Action", a national
programme designed to engage and support front-line clinicians to make
improvements to patient care. We identified reasons as to why our patients missed
appointments and then introduced a system to reduce "did not attend" (DNA) rates.
Non-attendance at appointments results in a waste of resources and increases
waiting times. It has been reported that DNA rates in mental health are higher
compared to other settings. Therefore, reducing DNA rates are a priority for
mental health care providers. We collected DNA rates over a period of months over
May 2013 to September 2013. We conducted a patient survey to inquire why the
patients missed their appointments. The aim of the project and results from the
survey were presented and discussed at the multi-disciplinary team meeting to
generate ideas for improvement and engage the team with the project. As the most
frequent response from the survey was 'forgetting the appointment', we decided to
introduce text messaging as an intervention to remind patients of their
appointments. We also ensured that staff updated the mobile phone records for the
patients at each appointment. We monitored the DNA rates after introducing this
change on a monthly basis. Following our intervention, there was an overall
reduction in DNA rates for all disciplines from 11.4% to 10.62% with the greatest
change for medical DNA's from 17.7% to 11.8 %. Results from a patient survey
showed that the reasons for non-attendance are multi-factorial and require a
complex approach. Our intervention was a simple one but still it demonstrated
some effectiveness. Reducing DNA rates requires interventions to be regularly
monitored so that their effect is sustained over a period of time.
PMID- 27493742
TI - Improving Mental Status Questionnaire (MSQ) completion on admission to the Acute
Surgical Receiving Unit (ASRU), Ninewells Hospital, Dundee.
AB - Delirium is common yet poorly identified in the UK. Early recognition is a key
prognostic factor; delay here being associated with: increased mortality,
increased morbidity, prolonged hospital stay, long term disability, and increased
risk of developing dementia. Improvement in the diagnosis and management of
delirium has scope to improve patient care, clinical outcomes, and ultimately an
improved patient experience. As patients aged >=75 years are at an increased risk
of developing delirium, we focused the improvement project to this age group. The
baseline data demonstrated that the average >=75 year-old patient admitted to the
Acute Surgical Receiving Unit (ASRU) at Ninewells Hospital had 5.4 out of 12
predisposing and precipitating risk factors for delirium; thus there was great
potential for delirium to develop in these patients. During the analysis of the
baseline data it became clear that we could not go ahead and implement the
initial proposed improvement as the completion of the mental status questionnaire
(MSQ) was inconsistent and low at 14.99%. Completion of the MSQ is vital in
establishing any cognitive deficit at admission, and for providing a baseline for
the continuing admission. As a consequence of this, we had to shift the main aim
of the improvement project from improving the identification, diagnosis, and
management of delirium, to improving the completion rate of the MSQ in our target
age group. Consultations with members of the admission team were held to
determine ways of improving the MSQ completion rate. It became clear that the
completion of the MSQ relied on clinical staff remembering all 10 questions that
constitute the test. The main intervention to facilitate improvement involved
affixing a sticker with all 10 questions of the MSQ within the admissions
document. The main aim was to increase the percentage of cognitive screening by
the Mental State Questionnaire (MSQ) to 95% in patients aged >=75 on admission to
ASRU at Ninewells Hospital by 11th July 2013. We achieved our main aim with 100%
compliance on two days. Our average compliance over six days was however 81.33%,
whilst not reaching our target this is still a substantial improvement. The
introduction of the sticker detailing the 10 MSQ questions within the ASRU
admissions document was well received by the admissions team. It has simplified
the process as members of staff do not need to rely on their memory to remember
the questions, and the sticker also acts as a prompt for them to consider further
cognitive screening.
PMID- 27493743
TI - Eliminating guidewire retention during ultrasound guided central venous catheter
insertion via an educational program, a modified CVC set, and a drape with
reminder stickers.
AB - Guidewire retention is a severe but preventable complication from central venous
catheter (CVC) insertion. There were three cases of guidewire retention during
CVC insertion in the medical intensive care unit (MICU) in Singapore General
Hospital, in the period between December 2011 and February 2012. The primary
objective of this quality improvement project was to eliminate future incidences
of guidewire retention during CVC insertion in the MICU and medical intermediate
care area (MICA) via a structured educational program and a cost effective
modified CVC set. The secondary objective was to perform a cost analysis and
comparison between the use of the conventional hospital CVC set and drape with
our newly modified CVC dressing kit. Root cause analysis of the three cases
identified major factors leading to guidewire retention. Interventions were
planned and tested using PDSA cycles. Internal medicine trainees rotating through
MICU and MICA during the period between February 2012 and June 2013 underwent a
multi-modal structured CVC insertion training program with hands on simulation.
They also used a newly modified CVC dressing kit and drape. The CVC dressing kit
was modified (CVC PLUS) to include a sterile drape with reminder stickers stating
"REMOVE the GUIDEWIRE," as well as a sterile ultrasound sleeve. The total number
of CVC insertions performed and guidewire retentions were monitored. During the
period of study there were 320 CVC insertions in the MICU and MICA. Since this
quality improvement project was initiated, and up to the submission of this
article, there have not been any further cases of guidewire retention in the MICU
and MICA. The total cost reduction per use of CVC PLUS was S$29.26 (Singaporean
Dollars). A multi-modal structured training program, integrated with a modified,
pre-packed CVC set, and drapes with reminder stickers (all included in CVC PLUS)
were cost effective, and improved patient safety by eliminating guidewire
retention during CVC insertion.
PMID- 27493744
TI - The Participative Design of an Endoscopy Facility using Lean 3P.
AB - In the UK, bowel cancer is the second largest cancer killer. Diagnosing people
earlier can save lives but demand for endoscopies is increasing and this can put
pressure on waiting times. To address this challenge, an endoscopy unit in North
East England decided to improve their facilities to increase capacity and create
environments that improve the experience of users. This presented a significant
opportunity for step change improvement but also a problem in terms of creating
designs that meet user requirements whilst addressing structural or space
constraints. The Lean design process known as '3P' (standing for the production
preparation process) was utilised as a participative design strategy to engage
stakeholders in the design of the new department. This involved a time-out
workshop (or 3P event) in which Lean and participative design tools were utilised
to create an innovative design based on 'point of delivery' (POD) principles. The
team created a design that demonstrated an increase in treatment room capacity by
25% and bed capacity by 70% whilst reducing travel distance for patients by 25.8%
and staff by 27.1%. This was achieved with an increase in available space of only
13%. The Lean 3P method provided a structured approach for corporate and clinical
staff to work together with patient representatives as cross-functional teams.
This participative approach facilitated communication and learning between
stakeholders about care processes and personal preferences. Lean 3P therefore
appears to be a promising approach to improving the healthcare facilities design
process to meet user requirements.
PMID- 27493745
TI - Improving the safety and efficiency of outpatient lumbar puncture service.
AB - Lumbar puncture (LP) is a commonly performed procedure in diagnosis and
management of neurological conditions. LP is generally safe, however there are a
number of potentially serious complications, including epidural haematoma and
cerebral herniation. The risks of these should be considered and minimised prior
to undertaking LP. Our regional neuroscience centre provides an outpatient LP
service for patients throughout southeast England. Referrals from distant
hospitals meant there was frequently no access to important clinical information,
including indication for LP, past medical history, or medication history until
the day of the procedure, and no access to results of investigations such as
coagulation profile, platelet count, or intracranial imaging. Furthermore, there
was limited capacity or time available in the day ward to perform these tests
prior to LP. As a result, patients were either having LPs cancelled on the day of
the procedure, were delayed by several hours on the day of the procedure for
investigations, or were subject to the risk of having the LP performed without
the knowledge of these key safety indicators. To address this issue we
implemented an LP safety checklist to be completed by referring neurologists,
providing details of the patient's medical history and results of investigations
performed locally. In doing this, we increased the proportion of patients with an
available platelet count prior to LP from 25% to 89%, and available coagulation
profile from 18% to 82%. In addition, we saw a qualitative increase in the
confidence of junior doctors in the safety of the LP clinic, as measured by a
survey taken before and after the implementation of this system. This simple
intervention made a rapid and remarkable difference to the safety and efficiency
of this outpatient LP clinic. We would encourage other units to adopt this
approach to address similar problems in a variety of outpatient settings.
PMID- 27493746
TI - Improving Pre-emptive Prescribing to Relieve Patient Discomfort Occurring Out of
Hours.
AB - Junior doctors are commonly asked to prescribe simple medications for symptom
relief for patients out of hours. Unfortunately, time constraints and other
pressures may lead to delays before the medications are prescribed. A quality
improvement project was conducted at a large university teaching hospital to
establish the extent of the problem, with the aim of finding measures to improve
preemptive prescribing for patients. Baseline data was gathered over three busy
wards to calculate the total of new prescriptions made over the course of a
weekend. There were 24 new prescriptions required over the weekend, a percentage
increase of 14.9% compared to the existing prescriptions on a Friday. Following
the first intervention this decreased to 10.2%, and by the second intervention
the rate was 4.9%. Data collected several months later confirmed that the
interventions remained successful, and preemptive prescribing continued. Overall,
our interventions have shown that the number of new prescriptions required out of
hours can be reduced by educating junior doctors on preemptive prescribing.
PMID- 27493747
TI - Improving the Physical Health Monitoring of City & Hackney Assertive Outreach
Service Patients.
AB - Improving physical healthcare to reduce premature mortality in people with SMI
(Serious Mental Illness) is a priority for ELFT (East London NHS Foundation
Trust) and NHS England. It is well know that people with schizophrenia have a
life expectancy which is approximately 20% shorter than that of the general
population and a substantial mortality difference exists between people with
schizophrenia and the general community.[1-2] Among other risk factors, such as
poor diet, physical inactivity, and high rates of smoking, the iatrogenic effects
of anti-psychotic medications have been found to increase the risk of metabolic
syndrome. This can easily be detected through regular monitoring. Through this
project, it was our aim to improve the physical health monitoring of City &
Hackney Assertive Outreach Service (AOS) patients with a view to decrease
mortality rate, increase life expectancy, increase the quality of life, and
reduce harm from medication. This was done using quality improvement methods,
including several change ideas, each of which started sequentially over the
course of a nine month period from November 2014. Following QI methodology, this
utilised cycles of iterative learning using PDSA methods and was supported by the
Trust's extensive programme of quality improvement, including training provided
by the Institute for Healthcare Improvement. The project involved setting a
specific aim which was improving the physical health monitoring of AOS patients
to 80% by July 2015 and for our patients to have physical health checks (blood
tests, weight, ECG, BP) as a minimum annually. From baseline measurements of
between 50-75%, we reached our target of 80% for weight, BP and blood tests
monitoring, with 89%, 91%, and 84% achieved respectively by July 2015. Further
progress still needs to be made on ECGs, with 77% achieved by July 2015, although
the monitoring of ECG nearly doubled from 39% in November 2014 to 77% in July
2015. This project demonstrated that effective leadership, collaborative team
work, embedding the project in our daily practice, generating local solutions,
and improved communication between primary and secondary care can increase the
physical health monitoring of this complex and challenging patient group. The
team continues to identify other areas for change that may lead to further
improvement in the physical health monitoring of AOS patients while making sure
that the improvement is sustained.
PMID- 27493748
TI - Red eyes and red-flags: improving ophthalmic assessment and referral in primary
care.
AB - Up to five percent of primary care consultations are eye-related, yet 96% of
General Practitioners (GPs) do not undergo postgraduate ophthalmology training.
Most do not feel assured performing eye assessments. Some red eye conditions can
become sight threatening, and often exhibit red-flag features. These features
include moderate pain, photophobia, reduced visual acuity (VA), eye-trauma, or
unilateral marked redness. The aim of this project was to improve primary care
assessment and referral of patients presenting with red-flag features based on
the NICE 'Red Eye' Clinical Knowledge Summary recommendations. Data was collected
retrospectively from 139 red eye consultations. A practice meeting highlighted
poor awareness of red-flag features, low confidence levels in eye assessments,
and time-constraints during appointments. Interventions were based on feedback
from staff. These included a primary care teaching session on red-flag features,
a VA measurement tutorial, and provision of a red eye toolkit, including VA
equipment, to each consultation room. At baseline, each patient had on average
0.9 red-flag features assessed. Only 36.0% (9/25) of patients with red-flag
features were appropriately referred to same-day ophthalmology services.
Following two improvement cycles, a significant improvement was seen in almost
every parameter. On average, each patient had 2.7 red-flag features assessed (vs
0.9, p<0.001). VA was assessed in 55.6% of consultations (vs 7.9%, p<0.001), pain
was quantified in 81.5% (vs 20.9%, p=0.005), eye-trauma or foreign-body (51.8% vs
8.6%, p<0.001), extent of redness was documented in 66.7% (vs 14.4%, p<0.001).
Only photophobia remained poorly assessed (18.5% vs 14.4%, p=0.75). Following
this, 75.0% (6/8) of patients were appropriately referred. This project reflected
the literature regarding low confidence and inexperience amongst GPs when faced
with ophthalmic conditions. Improvements in education are required to ensure
accurate assessments can be undertaken in a time-constrained environment.
PMID- 27493749
TI - Reducing CBC Clotting Rates in the Neonatal Patient Care Areas.
AB - Performing a complete blood count (CBC) is a common test performed in neonatal
intensive care. Samples reported as "clotted" are not able to be analyzed and
require redraw. A perceived "high" clotting rate elicits frustration among team
members and has negative effects on patient flow and patient satisfaction.
Process mapping and a root cause analysis determined that an educational
intervention was required to optimize blood collection skills of front-line
nurses. Through four rapid PDSA cycles over a three year period, the neonatal
patient care areas were able to decrease their CBC clotting rates from 30%
(monthly rate when the problem was identified) to 16% (yearly average at the end
of the project). The CBC clotting rates continue to decease over time due to the
integration of a multi-faceted educational plan into biannual education days
designed for current staff nurses, as well as into the orientation plan for newly
hired and student nurses.
PMID- 27493750
TI - Developing psychological services following facial trauma.
AB - Adults presenting to oral and maxillofacial surgery services are at high risk of
psychological morbidity. Research by the Institute of Psychotrauma and the centre
for oral and maxillofacial surgery trauma clinic at the Royal London hospital
(2015) demonstrated nearly 40% of patients met diagnostic criteria for either
depression, post traumatic stress disorder (PTSD), anxiety, alcohol misuse, or
substance misuse, or were presenting with facial appearance distress. Most facial
injury patients were not receiving mental health assessment or treatment, and the
maxillofacial team did not have direct access to psychological services. Based on
these research findings, an innovative one-year pilot psychology service was
designed and implemented within the facial trauma clinic. The project addressed
this need by offering collaborative medical and psychological care for all facial
injury patients. The project provided brief screening, assessment, and early
psychological intervention. The medical team were trained to better recognise and
respond to psychological distress.
PMID- 27493751
TI - Improving the communication between teams managing boarded patients on a surgical
specialty ward.
AB - Transferring patients from the ward of their specialty or consultant is described
as boarding. 1 Boarding patients is becoming increasingly prevalent due to
greater pressure on hospital capacity. This practice compromises patient safety
through delayed investigations, prolonged hospital stays, and increased risk of
hospital-acquired infections. 1 2 We evaluated how regularly boarded patients
were reviewed, and how effectively information regarding their management was
communicated from their primary specialty to ward staff. We aimed to improve the
frequency of patient reviews by ensuring that each patient was reviewed every
weekday and increase communication between primary specialty, and medical and
nursing teams by 20% from baseline during the data collection period. The project
was based in the Otolaryngology ward in Ninewells Hospital, Dundee, where there
was a high prevalence of boarded patients. Baseline data showed a clear deficit
in communication between the primary specialty and ward staff with only 31% of
patient reviews being communicated to ward doctors. We designed and implemented a
communication tool, in the form of a sticker, to be inserted into patients'
medical notes for use by the primary specialty. Implementation of the sticker
improved communication between teams as stickers were completed in 93% of
instances. In 88% of patient reviews, the junior doctor was informed of the
management plan, showing a large increase from baseline. Through PDSA cycles, we
aimed to increase the sustainability and reliability of the sticker; however, we
faced challenges with sustainability of sticker insertion. We aim to engage more
stakeholders to raise awareness of the problem, brainstorm solutions together,
and review the production and implementation of stickers with senior hospital
management to discuss the potential use of this tool within practice. There is
potentially a large scope for utilisation of this communication tool on a local
level, which we hope will significantly improve patient safety.
PMID- 27493752
TI - Promoting the role of patients in improving hand hygiene compliance amongst
health care workers.
AB - Hand hygiene is one of the fundamental measures necessary for reducing healthcare
associated infections. The adherence of health care workers to safe hand hygiene
practices is low worldwide, despite evidence showing compliance with hand hygiene
guidelines decreases infection rate. This project focuses on the role of patients
in promoting healthcare workers' compliance with hand hygiene practices. Several
plan-do-study-act (PDSA) cycles were conducted to test interventions which aimed
to empower patients and increase staff members' adherence to hand hygiene
practices. The initial findings presented on the run chart demonstrate that
compliance among healthcare workers increased with the interventions; there was
an increase of 15% compliance during the 10 days of project testing. We will need
to collect more data to show continued and sustained improvement. Patients can
play an important role in promoting safe care and hand hygiene practices.
PMID- 27493753
TI - Utilizing clinical pharmacists to improve delivery of evidence-based care for
depression and anxiety in primary care.
AB - Access to mental health providers has become an increasingly common challenge for
many patients with depression and anxiety disorders. Primary care providers often
manage this gap in care and currently provide solo care without the assistance of
other team members. In order to provide quality care that aligns with best
practice, we developed a depression and anxiety disorder treatment pathway
utilizing a multidisciplinary team based on each members' individual skill set,
or skill-task alignment. The main change to treatment implemented by the pathway
was the addition of a clinical pharmacist in the management of patient care. This
pathway was trialed over five months targeting two adult primary care teams
(approximately 34 physicians and Advanced Registered Nurse Practitioners [ARNPs])
while the other five teams continued with current practice standards. Post
implementation metrics indicated that clinical pharmacists successfully contacted
55% (406 of 738) of patients started on medication or who had a medication
changed. Of these patients reached, 82 (20%) had an intervention completed. In
addition, all physician leaders on the planning team (n=6) stated the new pathway
was well received and delivered positive feedback from team members.
PMID- 27493754
TI - Preliminary study of novel, timed walking tests for children with spina bifida or
cerebral palsy.
AB - OBJECTIVE: Walking assessment is an important aspect of rehabilitation practice;
yet, clinicians have few psychometrically sound options for evaluating walking in
highly ambulatory children. The purpose of this study was to evaluate the
validity and reliability of two new measures of walking function-the Obstacles
and Curb tests-relative to the 10-Meter Walk test and Timed Up and Go test in
children with spina bifida or cerebral palsy. METHODS: A total of 16 ambulatory
children with spina bifida (n=9) or cerebral palsy (n=7) (9 boys; mean age
7years, 7months; standard deviation 3years, 4months) and 16 age- and gender
matched typically developing children participated. Children completed the
walking tests, at both self-selected and fast speeds, twice. To evaluate
discriminative validity, scores were compared between typically developing and
spina bifida/cerebral palsy groups. Within the spina bifida/cerebral palsy group,
inter-test correlations evaluated convergent validity and intraclass correlation
coefficients evaluated within-session test-retest reliability. RESULTS: At fast
speeds, all tests showed discriminative validity (p<0.006 for typically
developing and spina bifida/cerebral palsy comparisons) and convergent validity
(rho=0.81-0.90, p?0.001, for inter-test correlations). At self-selected speeds,
only the Obstacles test discriminated between groups (p=0.001). Moderately strong
correlations (rho=0.73-0.78, p?0.001) were seen between the 10-Meter Walk test,
Curb test, and Timed Up and Go test. Intraclass correlation coefficients ranged
from 0.81 to 0.97, with higher test-retest reliability for tests performed at
fast speeds rather than self-selected speeds. CONCLUSION: The Obstacles and Curb
tests are promising measures for assessing walking in this population. Performing
tests at fast walking speeds may improve their validity and test-retest
reliability for children with spina bifida/cerebral palsy.
PMID- 27493755
TI - Non-invasive assessment of peripheral arterial disease: Automated ankle brachial
index measurement and pulse volume analysis compared to duplex scan.
AB - OBJECTIVES: This cross-sectional study aimed to individually and cumulatively
compare sensitivity and specificity of the (1) ankle brachial index and (2) pulse
volume waveform analysis recorded by the same automated device, with the presence
or absence of peripheral arterial disease being verified by ultrasound duplex
scan. METHODS: Patients (n=205) referred for lower limb arterial assessment
underwent ankle brachial index measurement and pulse volume waveform recording
using volume plethysmography, followed by ultrasound duplex scan. The presence of
peripheral arterial disease was recorded if ankle brachial index <0.9; pulse
volume waveform was graded as 2, 3 or 4; or if haemodynamically significant
stenosis >50% was evident with ultrasound duplex scan. Outcome measure was
agreement between the measured ankle brachial index and interpretation of pulse
volume waveform for peripheral arterial disease diagnosis, using ultrasound
duplex scan as the reference standard. RESULTS: Sensitivity of ankle brachial
index was 79%, specificity 91% and overall accuracy 88%. Pulse volume waveform
sensitivity was 97%, specificity 81% and overall accuracy 85%. The combined
sensitivity of ankle brachial index and pulse volume waveform was 100%,
specificity 76% and overall accuracy 85%. CONCLUSION: Combining these two
diagnostic modalities within one device provided a highly accurate method of
ruling out peripheral arterial disease, which could be utilised in primary care
to safely reduce unnecessary secondary care referrals.
PMID- 27493756
TI - Implementation and evaluation of Stanford Health Care direct-care teledermatology
program.
AB - INTRODUCTION: Teledermatology has proven to be an effective means of providing
dermatologic care. The existing research has primarily evaluated its usefulness
in a consultative model. Few academic centers have evaluated a patient-initiated
model, and direct-to-consumer services remain the subject of controversy.
Stanford Health Care recently launched a direct-care, patient-initiated
teledermatology pilot program. This article evaluates the viability and patient
satisfaction with this service. MATERIALS AND METHODS: During the pilot period,
patients were able to seek remote dermatologic care using an eVisit tool in their
MyHealth account. Patients initiated the consultation, answered questions
regarding their complaint, and uploaded a picture if relevant. A Stanford
dermatologist reviewed each eVisit and responded with an assessment and plan. The
dermatologist noted whether they were able to make a diagnosis and their level of
confidence in it. After the study, 10 patients participated in a focus group to
provide feedback on the service. RESULTS: In all, 38 patients sought care during
the pilot period. A dermatologist was able to make a diagnosis in 36 of 38 (95%)
cases, with an average confidence level of 7.9 of 10. The average time to
consultation was 0.8 days. Patients indicated high levels of satisfaction with
the service although they had suggestions for improvement. DISCUSSION: Patients
provided clinically useful images and information in a direct-care
teledermatology model. Such services allow dermatology providers to increase
access while maintaining high-quality care in an academic medical center. Further
research is needed on standalone services that cannot integrate encounters with
the patient's existing medical record.
PMID- 27493757
TI - A randomized controlled trial studying the effectiveness of group medical
appointments on self-efficacy and adherence in sickle cell disease (TEAM study):
study protocol.
AB - BACKGROUND: Sickle cell disease (SCD) is endemic in non-Western countries. Due to
migration, the prevalence of SCD in the Netherlands has increased. Adherence to
medical treatment is recognized as a major problem area. Therefore, new effective
interventions to increase adherence are urgently needed. METHODS/DESIGN: The TEAM
study is an ongoing randomized controlled trial (RCT) to compare protocolized
individual medical appointments (IMA's; care-as-usual) with protocolized group
medical appointments (GMA's; novel intervention) in pediatric (n = 40) and adult
(n = 60) patients. The study aims to assess the effectiveness of GMA's (over a
three year period) on patients' self-efficacy, adherence, quality of life,
morbidity, hospital admissions and satisfaction with the treating professional;
as well as to test the cost-effectiveness of GMA's. In both the IMA and GMA
groups structured assessments will be performed at baseline (start of the study),
after 1.5 and after 3 years. DISCUSSION: This is the first RCT to investigate the
effectiveness of GMA's on self-efficacy and adherence in pediatric and adult
patients with SCD, including a cost-effectiveness analysis. TRIAL REGISTRATION:
NTR4750 (NL42182.000.12). Registered 13 August 2014.
PMID- 27493758
TI - "Lachnoclostridium bouchesdurhonense," a new bacterial species isolated from
human gut microbiota.
AB - We report the main characteristics of "Lachnoclostridium bouchesdurhonense"
strain AT5(T) (=CSUR P2181), a new bacterial species isolated from the gut
microbiota of an obese patient from Marseille.
PMID- 27493759
TI - Cardiovascular disease risk factors in relation to smoking behaviour and history:
a population-based cohort study.
AB - OBJECTIVE: To investigate how individual risk factors for cardiovascular disease
(CVD) (blood pressure, lipid levels, body mass index, waist and hip
circumference, use of antihypertensive or hypolipidemic medication, and diagnosed
diabetes) differ in people aged 46 years with different smoking behaviour and
history. METHODS: This population-based cohort study is based on longitudinal
data from the Northern Finland Birth Cohort 1966 project. Data were collected at
the 31-year and 46-year follow-ups, when a total of 5038 and 5974 individuals
participated in clinical examinations and questionnaires. Data from both follow
ups were available for 3548 participants. In addition to individual CVD risk
factors, Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms
were used to assess the absolute risk of a CVD event within the next decade.
RESULTS: The differences in individual risk factors for CVD reached statistical
significance for some groups, but the differences were not consistent or
clinically significant. There were no clinically significant differences in CVD
risk as measured by Framingham or SCORE algorithms between never smokers, recent
quitters and former smokers (7.5%, 7.4%, 8.1% for men; 3.3%, 3.0%, 3.2% for
women; p<0.001). CONCLUSIONS: The effect of past or present smoking on individual
CVD risk parameters such as blood pressure and cholesterol seems to be of
clinically minor significance in people aged 46 years. In other words, smoking
seems to be above all an independent risk factor for CVD in the working-age
population. Quitting smoking in working age may thus reduce calculated CVD risk
nearly to the same level with people who have never smoked.
PMID- 27493760
TI - Sudden cardiac death in adults with congenitally corrected transposition of the
great arteries.
AB - BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is
a rare congenital heart disease. There have been only few reports of sudden
cardiac death (SCD) in patients with ccTGA and reasonable ventricular function.
METHODS: A retrospective review of the medical records of all patients attending
our adult congenital heart centre, with known ccTGA. RESULTS: From a database of
over 3500 adult patients with congenital heart disease, we identified 39 (~1%)
with ccTGA and 'two-ventricle' circulations. 65% were male. The mean age at
diagnosis was 12.4+/-11.4 years and the mean age at last time of review was
34.3+/-11.3 years. 24 patients (56%) had a history of surgical intervention. 8
(19%) had had pacemaker implantation and 2 had had a defibrillator implanted for
non-sustained ventricular tachycardia (NSVT). In 544 years of patient follow-up,
there had been five cases of SCD in our population; 1 death per 109 patient
years. Two of these patients had had previously documented supraventricular or
NSVT. However, they were all classified as New York Heart Association (NYHA)
class I or II, and systemic (right) ventricular function had been recorded as
normal, mildly or mildly-moderately impaired, at most recent follow-up.
CONCLUSIONS: Our experience suggests the need for improved risk stratification
and/or surveillance for malignant arrhythmia in adults with ccTGA, even in those
with reasonable functional class on ventricular function.
PMID- 27493761
TI - Coronary sinus-based percutaneous annuloplasty as treatment for functional mitral
regurgitation: the TITAN II trial.
AB - OBJECTIVE: Functional (or secondary) mitral regurgitation (FMR) is associated
with greater morbidity and worse outcomes in patients with congestive heart
failure (CHF) and cardiomyopathy. The Carillon(r) Mitral Contour System(r) is a
coronary sinus-based percutaneous therapy to reduce FMR. We evaluated the safety
and efficacy of a modified version of the Carillon device in the treatment of
patients with cardiomyopathy and FMR. METHODS: 36 patients with CHF, depressed
left ventricular function (ejection fraction <40%) and at least moderate FMR
underwent the Carillon device implant. RESULTS: There was 1 major adverse event
within 30 days-a death (not device related)-occurring 17 days after the implant.
Reductions in FMR and improvements in functional class and 6 min walk tests were
seen, similar to prior studies. Device fractures in the high strain region of the
proximal anchor (seen in prior studies) were not seen in this study. CONCLUSIONS:
The modified Carillon device was associated with improvements in clinical and
echocardiographic parameters in treating patients with FMR, while successfully
addressing the issue of anchor fracture. This version of the Carillon device will
be used in a blinded randomised trial of symptomatic patients with FMR.
PMID- 27493762
TI - Circulating miRNA in patients with non-alcoholic fatty liver disease and coronary
artery disease.
AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the hepatic
manifestation of metabolic syndrome and coronary artery disease (CAD) is the
cardiac manifestation of metabolic syndrome. NAFLD is strongly linked to CAD and
hepatic steatosis is an independent risk factor for CAD and cardiac mortality.
The pathogenic mechanism underlying this association remains poorly understood.
In this study, we explored expression of circulating microRNAs (miRNAs) in
patients with NAFLD and associated CAD. RESULTS: When compared to patients with
NAFLD without CAD, patients with NAFLD and CAD had lower circulating levels of
miR-132 (0.24+/-0.16 vs 0.30+/-0.11, p=0.03), while the circulating levels of miR
143 were higher (0.96+/-0.90 vs 0.64+/-0.77, p=0.02). The levels in circulation
demonstrated trends opposite to previously observed intracellular levels in
patients with CAD. In obese patients with NAFLD, lower circulating levels of miR
145 (1.42+/-1.00 vs 2.41+/-1.80), miR-211 (41.26+/-20.40 vs 57.56+/-25.45), miR
146a (2.13+/-1.40 vs 2.90+/-1.36) and miR-30c (6.92+/-4.99 vs 11.0+/-6.92) were
detected when compared to lean patients with NAFLD. For miR-161 (0.59+/-1.19 vs
0.15+/-0.14) and miR-241 (0.28+/-0.29 vs 0.16+/-0.13), higher circulatory levels
were detected in the obese patients with NAFLD. These observations suggest
altered circulating levels of miRNAs that may serve to balance intracellular
levels of miRNA in target tissues. Additional studies examining paired samples of
target and producing tissues as well as respective plasma samples will help
delineate the regulatory circuits governing the secretion and the uptake of miRNA
in multitissue diseases.
PMID- 27493763
TI - Sex differences in disease presentation, treatment and clinical outcomes of
patients with hepatocellular carcinoma: a single-centre cohort study.
AB - BACKGROUND: Although sex differences in hepatocellular carcinoma (HCC) risk are
well known, it is unclear whether sex differences also exist in clinical
presentation and survival outcomes once HCC develops. METHODS: We performed a
retrospective cohort study of 1886 HCC patients seen in a US medical centre in
1998-2015. Data were obtained by chart review with survival data also by National
Death Index search. RESULTS: The cohort consisted of 1449 male and 437 female
patients. At diagnosis, men were significantly younger than women (59.9+/-10.7 vs
64.0+/-11.6, p<0.0001). Men had significantly higher rates of tobacco (57.7% vs
31.0%, p<0.001) and alcohol use (63.2% vs 35.1%, p<0.001). Women were more likely
to be diagnosed by routine screening versus symptomatically or incidentally
(65.5% vs 58.2%, p=0.03) and less likely to present with tumours >5 cm (30.2% vs
39.8%, p=0.001). Surgical and non-surgical treatment utilisation was similar for
both sexes. Men and women had no significant difference in median survival from
the time of diagnosis (median 30.7 (range=24.5-41.3) vs 33.1 (range=27.4-37.3)
months, p=0.84). On multivariate analysis, significant predictors for improved
survival included younger age, surgical or non-surgical treatment (vs supportive
care), diagnosis by screening, tumour within Milan criteria and lower Model for
End-Stage Liver Disease score, but not female sex (adjusted HR=1.01, CI 0.82 to
1.24, p=0.94). CONCLUSIONS: Although men have much higher risk for HCC
development, there were no significant sex differences in disease presentation or
survival except for older age and lower tumour burden at diagnosis in women.
Female sex was not an independent predictor for survival.
PMID- 27493764
TI - Is this scaling nonlinear?
AB - One of the most celebrated findings in complex systems in the last decade is that
different indexes y (e.g. patents) scale nonlinearly with the population x of the
cities in which they appear, i.e. y~x (beta) ,beta?1. More recently, the
generality of this finding has been questioned in studies that used new databases
and different definitions of city boundaries. In this paper, we investigate the
existence of nonlinear scaling, using a probabilistic framework in which
fluctuations are accounted for explicitly. In particular, we show that this
allows not only to (i) estimate beta and confidence intervals, but also to (ii)
quantify the evidence in favour of beta?1 and (iii) test the hypothesis that the
observations are compatible with the nonlinear scaling. We employ this framework
to compare five different models to 15 different datasets and we find that the
answers to points (i)-(iii) crucially depend on the fluctuations contained in the
data, on how they are modelled, and on the fact that the city sizes are heavy
tailed distributed.
PMID- 27493765
TI - State-space reduction and equivalence class sampling for a molecular self
assembly model.
AB - Direct simulation of a model with a large state space will generate enormous
volumes of data, much of which is not relevant to the questions under study. In
this paper, we consider a molecular self-assembly model as a typical example of a
large state-space model, and present a method for selectively retrieving 'target
information' from this model. This method partitions the state space into
equivalence classes, as identified by an appropriate equivalence relation. The
set of equivalence classes H, which serves as a reduced state space, contains
none of the superfluous information of the original model. After construction and
characterization of a Markov chain with state space H, the target information is
efficiently retrieved via Markov chain Monte Carlo sampling. This approach
represents a new breed of simulation techniques which are highly optimized for
studying molecular self-assembly and, moreover, serves as a valuable guideline
for analysis of other large state-space models.
PMID- 27493766
TI - New information on the braincase and inner ear of Euparkeria capensis Broom:
implications for diapsid and archosaur evolution.
AB - Since its discovery, Euparkeria capensis has been a key taxon for understanding
the early evolution of archosaurs. The braincase of Euparkeria was described
based on a single specimen, but much uncertainty remained. For the first time,
all available braincase material of Euparkeria is re-examined using micro
computed tomography scanning. Contrary to previous work, the parabasisphenoid
does not form the posterior border of the fenestra ovalis in lateral view, but it
does bear a dorsal projection that forms the anteroventral half of the fenestra.
No bone pneumatization was found, but the lateral depression of the
parabasisphenoid may have been pneumatic. We propose that the lateral depression
likely corresponds to the anterior tympanic recess present in crown archosaurs.
The presence of a laterosphenoid is confirmed for Euparkeria. It largely conforms
to the crocodilian condition, but shows some features which make it more similar
to the avemetatarsalian laterosphenoid. The cochlea of Euparkeria is elongated,
forming a deep cochlear recess. In comparison with other basal archosauromorphs,
the metotic foramen is much enlarged and regionalized into vagus and recessus
scalae tympani areas, indicating an increase in its pressure-relief mechanism.
The anterior semicircular canal is extended and corresponds to an enlarged
floccular fossa. These aspects of the braincase morphology may be related to the
development of a more upright posture and active lifestyle. They also indicate
further adaptations of the hearing system of Euparkeria to terrestriality.
PMID- 27493768
TI - Cold-stress responses in the Antarctic basidiomycetous yeast Mrakia blollopis.
AB - Microbes growing at subzero temperatures encounter numerous growth constraints.
However, fungi that inhabit cold environments can grow and decompose organic
compounds under subzero temperatures. Thus, understanding the cold-adaptation
strategies of fungi under extreme environments is critical for elucidating polar
region ecosystems. Here, I report that two strains of the Antarctic
basidiomycetous yeast Mrakia blollopis exhibited distinct growth characteristics
under subzero conditions: SK-4 grew efficiently, whereas TKG1-2 did not. I
analysed the metabolite responses elicited by cold stress in these two M.
blollopis strains by using capillary electrophoresis-time-of-flight mass
spectrometry. M. blollopis SK-4, which grew well under subzero temperatures,
accumulated high levels of TCA-cycle metabolites, lactic acid, aromatic amino
acids and polyamines in response to cold shock. Polyamines are recognized to
function in cell-growth and developmental processes, and aromatic amino acids are
also known to improve cell growth at low temperatures. By contrast, in TKG1-2,
which did not grow efficiently, cold stress strongly induced the metabolites of
the TCA cycle, but other metabolites were not highly accumulated in the cell.
Thus, these differences in metabolite responses could contribute to the distinct
abilities of SK-4 and TKG1-2 cells to grow under subzero temperature conditions.
PMID- 27493767
TI - Pupil dilation as an index of preferred mutual gaze duration.
AB - Most animals look at each other to signal threat or interest. In humans, this
social interaction is usually punctuated with brief periods of mutual eye
contact. Deviations from this pattern of gazing behaviour generally make us feel
uncomfortable and are a defining characteristic of clinical conditions such as
autism or schizophrenia, yet it is unclear what constitutes normal eye contact.
Here, we measured, across a wide range of ages, cultures and personality types,
the period of direct gaze that feels comfortable and examined whether autonomic
factors linked to arousal were indicative of people's preferred amount of eye
contact. Surprisingly, we find that preferred period of gaze duration is not
dependent on fundamental characteristics such as gender, personality traits or
attractiveness. However, we do find that subtle pupillary changes, indicative of
physiological arousal, correlate with the amount of eye contact people find
comfortable. Specifically, people preferring longer durations of eye contact
display faster increases in pupil size when viewing another person than those
preferring shorter durations. These results reveal that a person's preferred
duration of eye contact is signalled by physiological indices (pupil dilation)
beyond volitional control that may play a modulatory role in gaze behaviour.
PMID- 27493769
TI - Optimal switching between geocentric and egocentric strategies in navigation.
AB - Animals use a combination of egocentric navigation driven by the internal
integration of environmental cues, interspersed with geocentric course correction
and reorientation. These processes are accompanied by uncertainty in sensory
acquisition of information, planning and execution. Inspired by observations of
dung beetle navigational strategies that show switching between geocentric and
egocentric strategies, we consider the question of optimal reorientation rates
for the navigation of an agent moving along a preferred direction in the presence
of multiple sources of noise. We address this using a model that takes the form
of a correlated random walk at short time scales that is punctuated by
reorientation events leading to a biased random walks at long time scales. This
allows us to identify optimal alternation schemes and characterize their
robustness in the context of noisy sensory acquisition as well as performance
errors linked with variations in environmental conditions and agent-environment
interactions.
PMID- 27493770
TI - Camp stability predicts patterns of hunter-gatherer cooperation.
AB - Humans regularly cooperate with non-kin, which has been theorized to require
reciprocity between repeatedly interacting and trusting individuals. However, the
role of repeated interactions has not previously been demonstrated in explaining
real-world patterns of hunter-gatherer cooperation. Here we explore cooperation
among the Agta, a population of Filipino hunter-gatherers, using data from both
actual resource transfers and two experimental games across multiple camps.
Patterns of cooperation vary greatly between camps and depend on socio-ecological
context. Stable camps (with fewer changes in membership over time) were
associated with greater reciprocal sharing, indicating that an increased
likelihood of future interactions facilitates reciprocity. This is the first
study reporting an association between reciprocal cooperation and hunter-gatherer
band stability. Under conditions of low camp stability individuals still acquire
resources from others, but do so via demand sharing (taking from others), rather
than based on reciprocal considerations. Hunter-gatherer cooperation may either
be characterized as reciprocity or demand sharing depending on socio-ecological
conditions.
PMID- 27493771
TI - Mating success and body condition not related to foraging specializations in male
fur seals.
AB - Individual specialization is widespread among wild populations. While its fitness
consequences are central in predicting the ecological and evolutionary
trajectories of populations, they remain poorly understood. Long-term individual
foraging specializations occur in male Antarctic (Arctocephalus gazella) and
Australian (A. pusillus doriferus) fur seals. Strong selective pressure is
expected in these highly dimorphic and polygynous species, raising the question
of the fitness payoffs associated with different foraging strategies. We
investigated the relationship between individual isotopic niche (a proxy of
foraging specialization), body size and condition, and an index of reproductive
success (harem size) in territorial males. Individuals varied greatly in their
skin and fur isotopic values reflecting a range of foraging strategies within the
two populations. However, in both species, isotopic niche was not correlated to
body size, condition or mating success (R (2)/rho < 0.06). Furthermore, no
foraging niche was predominant in either species, which would have indicated a
substantial long-term fitness benefit of a particular strategy via a higher
survival rate. These results suggest that the fitness consequences of a foraging
strategy depend not only on the quality of prey and feeding habitat but also on
an individual's hunting efficiency and skills.
PMID- 27493772
TI - Does density influence relative growth performance of farm, wild and F1 hybrid
Atlantic salmon in semi-natural and hatchery common garden conditions?
AB - The conditions encountered by Atlantic salmon, Salmo salar L., in aquaculture are
markedly different from the natural environment. Typically, farmed salmon
experience much higher densities than wild individuals, and may therefore have
adapted to living in high densities. Previous studies have demonstrated that
farmed salmon typically outgrow wild salmon by large ratios in the hatchery, but
these differences are much less pronounced in the wild. Such divergence in growth
may be explained partly by the offspring of wild salmon experiencing higher
stress and thus lower growth when compared under high-density farming conditions.
Here, growth of farmed, wild and F1 hybrid salmon was studied at contrasting
densities within a hatchery and semi-natural environment. Farmed salmon
significantly outgrew hybrid and wild salmon in all treatments. Importantly,
however, the reaction norms were similar across treatments for all groups. Thus,
this study was unable to find evidence that the offspring of farmed salmon have
adapted more readily to higher fish densities than wild salmon as a result of
domestication. It is suggested that the substantially higher growth rate of
farmed salmon observed in the hatchery compared with wild individuals may not
solely be caused by differences in their ability to grow in high-density hatchery
scenarios.
PMID- 27493773
TI - User-based representation of time-resolved multimodal public transportation
networks.
AB - Multimodal transportation systems, with several coexisting services like bus,
tram and metro, can be represented as time-resolved multilayer networks where the
different transportation modes connecting the same set of nodes are associated
with distinct network layers. Their quantitative description became possible
recently due to openly accessible datasets describing the geo-localized
transportation dynamics of large urban areas. Advancements call for novel
analytics, which combines earlier established methods and exploits the inherent
complexity of the data. Here, we provide a novel user-based representation of
public transportation systems, which combines representations, accounting for the
presence of multiple lines and reducing the effect of spatial embeddedness, while
considering the total travel time, its variability across the schedule, and
taking into account the number of transfers necessary. After the adjustment of
earlier techniques to the novel representation framework, we analyse the public
transportation systems of several French municipal areas and identify hidden
patterns of privileged connections. Furthermore, we study their efficiency as
compared to the commuting flow. The proposed representation could help to enhance
resilience of local transportation systems to provide better design policies for
future developments.
PMID- 27493774
TI - Active and reactive behaviour in human mobility: the influence of attraction
points on pedestrians.
AB - Human mobility is becoming an accessible field of study, thanks to the progress
and availability of tracking technologies as a common feature of smart phones. We
describe an example of a scalable experiment exploiting these circumstances at a
public, outdoor fair in Barcelona (Spain). Participants were tracked while
wandering through an open space with activity stands attracting their attention.
We develop a general modelling framework based on Langevin dynamics, which allows
us to test the influence of two distinct types of ingredients on mobility:
reactive or context-dependent factors, modelled by means of a force field
generated by attraction points in a given spatial configuration and active or
inherent factors, modelled from intrinsic movement patterns of the subjects. The
additive and constructive framework model accounts for some observed features.
Starting with the simplest model (purely random walkers) as a reference, we
progressively introduce different ingredients such as persistence, memory and
perceptual landscape, aiming to untangle active and reactive contributions and
quantify their respective relevance. The proposed approach may help in
anticipating the spatial distribution of citizens in alternative scenarios and in
improving the design of public events based on a facts-based approach.
PMID- 27493775
TI - Contrast, contours and the confusion effect in dazzle camouflage.
AB - 'Motion dazzle camouflage' is the name for the putative effects of highly
conspicuous, often repetitive or complex, patterns on parameters important in
prey capture, such as the perception of speed, direction and identity. Research
into motion dazzle camouflage is increasing our understanding of the interactions
between visual tracking, the confusion effect and defensive coloration. However,
there is a paucity of research into the effects of contrast on motion dazzle
camouflage: is maximal contrast a prerequisite for effectiveness? If not, this
has important implications for our recognition of the phenotype and understanding
of the function and mechanisms of potential motion dazzle camouflage patterns.
Here we tested human participants' ability to track one moving target among many
identical distractors with surface patterns designed to test the influence of
these factors. In line with previous evidence, we found that targets with stripes
parallel to the object direction of motion were hardest to track. However,
reduction in contrast did not significantly influence this result. This finding
may bring into question the utility of current definitions of motion dazzle
camouflage, and means that some animal patterns, such as aposematic or mimetic
stripes, may have previously unrecognized multiple functions.
PMID- 27493776
TI - Gestational experience alters sex allocation in the subsequent generation.
AB - Empirical tests of adaptive maternal sex allocation hypotheses have presented
inconsistent results in mammals. The possibility that mothers are constrained in
their ability to adjust sex ratios could explain some of the remaining variation.
Maternal effects, the influence of the maternal phenotype or genotype on her
developing offspring, may constrain sex allocation through physiological changes
in response to the gestational environment. We tested if maternal effects
constrain future parental sex allocation through a lowered gestational stress
environment in laboratory mice. Females that experienced lowered stress as
embryos in utero gave birth to female-biased litters as adults, with no change to
litter size. Changes in offspring sex ratio was linked to peri-conceptual
glucose, as those females that had increasing blood glucose peri-conceptionally
gave birth to litters with a higher male to female sex ratio. There was, however,
no effect of the lowered prenatal stress for developing male embryos and their
sperm sex ratio when adult. We discuss the implications of maternal effects and
maternal stress environment on the lifelong physiology of the offspring,
particularly as a constraint on later maternal sex allocation.
PMID- 27493777
TI - Alcohol discrimination and preferences in two species of nectar-feeding primate.
AB - Recent reports suggest that dietary ethanol, or alcohol, is a supplemental source
of calories for some primates. For example, slow lorises (Nycticebus coucang)
consume fermented nectars with a mean alcohol concentration of 0.6% (range: 0.0
3.8%). A similar behaviour is hypothesized for aye-ayes (Daubentonia
madagascariensis) based on a single point mutation (A294V) in the gene that
encodes alcohol dehydrogenase class IV (ADH4), the first enzyme to catabolize
alcohol during digestion. The mutation increases catalytic efficiency 40-fold and
may confer a selective advantage to aye-ayes that consume the nectar of Ravenala
madagascariensis. It is uncertain, however, whether alcohol exists in this nectar
or whether alcohol is preferred or merely tolerated by nectarivorous primates.
Here, we report the results of a multiple-choice food preference experiment with
two aye-ayes and a slow loris. We conducted observer-blind trials with
randomized, serial dilutions of ethanol (0-5%) in a standard array of nectar
simulating sucrose solutions. We found that both species can discriminate varying
concentrations of alcohol; and further, that both species prefer the highest
available concentrations. These results bolster the hypothesized adaptive
function of the A294V mutation in ADH4, and a connection with fermented foods,
both in aye-ayes and the last common ancestor of African apes and humans.
PMID- 27493778
TI - Anthropogenic noise, but not artificial light levels predicts song behaviour in
an equatorial bird.
AB - Birds in cities start singing earlier in the morning than in rural areas;
commonly this shift is attributed to light pollution. Some studies have suggested
that traffic noise has a stronger influence on singing activity than artificial
light does. Changes in the timing of singing behaviour in relation to noise and
light pollution have only been investigated in the temperate zones. Tropical
birds, however, experience little seasonal variation in day length and may be
less dependent on light intensity as a modifier for reproductive behaviours such
as song. To test whether noise or light pollution has a stronger impact on the
dawn chorus of a tropical bird, we investigated the singing behaviour of rufous
collared sparrows (Zonotrichia capensis) in Bogota, Colombia at two times during
the year. We found that birds in places with high noise levels started to sing
earlier. Light pollution did not have a significant effect. Birds may begin to
sing earlier in noisy areas to avoid acoustic masking by traffic later in the
morning. Our results also suggest that some tropical birds may be less sensitive
to variations in day length and thus less sensitive to light pollution.
PMID- 27493779
TI - Network connections, dyadic bonds and fitness in wild female baboons.
AB - In many social mammals, females who form close, differentiated bonds with others
experience greater offspring survival and longevity. We still know little,
however, about how females' relationships are structured within the social group,
or whether connections beyond the level of the dyad have any adaptive value.
Here, we apply social network analysis to wild baboons in order to evaluate the
comparative benefits of dyadic bonds against several network measures. Results
suggest that females with strong dyadic bonds also showed high eigenvector
centrality, a measure of the extent to which an individual's partners are
connected to others in the network. Eigenvector centrality was a better predictor
of offspring survival than dyadic bond strength. Previous results have shown that
female baboons derive significant fitness benefits from forming close, stable
bonds with several other females. Results presented here suggest that these
benefits may be further augmented if a female's social partners are themselves
well connected to others within the group rather than being restricted to a
smaller clique.
PMID- 27493780
TI - Social networks predict selective observation and information spread in ravens.
AB - Animals are predicted to selectively observe and learn from the conspecifics with
whom they share social connections. Yet, hardly anything is known about the role
of different connections in observation and learning. To address the
relationships between social connections, observation and learning, we
investigated transmission of information in two raven (Corvus corax) groups.
First, we quantified social connections in each group by constructing networks on
affiliative interactions, aggressive interactions and proximity. We then seeded
novel information by training one group member on a novel task and allowing
others to observe. In each group, an observation network based on who observed
whose task-solving behaviour was strongly correlated with networks based on
affiliative interactions and proximity. Ravens with high social centrality
(strength, eigenvector, information centrality) in the affiliative interaction
network were also central in the observation network, possibly as a result of
solving the task sooner. Network-based diffusion analysis revealed that the order
that ravens first solved the task was best predicted by connections in the
affiliative interaction network in a group of subadult ravens, and by social rank
and kinship (which influenced affiliative interactions) in a group of juvenile
ravens. Our results demonstrate that not all social connections are equally
effective at predicting the patterns of selective observation and information
transmission.
PMID- 27493781
TI - Overwintering evergreen oaks reverse typical relationships between leaf traits in
a species spectrum.
AB - The leaf economics spectrum has given us a fundamental understanding of the
species variations in leaf variables. Across plant species, tight correlations
among leaf mass per area (LMA), mass-based nitrogen (N m) and photosynthetic rate
(A m) and leaf lifespan have been well known as trade-offs in leaf carbon
economy. However, the regional or biome-level correlations may not be necessary
to correspond with the global-scale analysis. Here, we show that almost all leaf
variables in overwintering evergreen oaks in Japan were relatively well included
within the evergreen-broadleaved trees in worldwide temperate forests, but N m
was more consistent with that in deciduous broadleaved trees. Contrary to the
universal correlations, the correlation between A m and N m among the evergreen
oaks was negative and the correlation between A m and LMA disappeared. The unique
performance was due to specific nitrogen allocation within leaves, i.e. the
evergreen oaks with later leaf maturation had lower N m but higher nitrogen
allocation to photosynthetic enzymes within leaves, to enhance carbon gain
against the delayed leaf maturation and the shortened photosynthetic period due
to cold winters. Our data demonstrate that correlations between leaf variables in
a local scale are occasionally different from averaged global-scale datasets,
because of the constraints in each biome.
PMID- 27493782
TI - Population structure and historical demography of South American sea lions
provide insights into the catastrophic decline of a marine mammal population.
AB - Understanding the causes of population decline is crucial for conservation
management. We therefore used genetic analysis both to provide baseline data on
population structure and to evaluate hypotheses for the catastrophic decline of
the South American sea lion (Otaria flavescens) at the Falkland Islands
(Malvinas) in the South Atlantic. We genotyped 259 animals from 23 colonies
across the Falklands at 281 bp of the mitochondrial hypervariable region and 22
microsatellites. A weak signature of population structure was detected, genetic
diversity was moderately high in comparison with other pinniped species, and no
evidence was found for the decline being associated with a strong demographic
bottleneck. By combining our mitochondrial data with published sequences from
Argentina, Brazil, Chile and Peru, we also uncovered strong maternally directed
population structure across the geographical range of the species. In particular,
very few shared haplotypes were found between the Falklands and South America,
and this was reflected in correspondingly low migration rate estimates. These
findings do not support the prominent hypothesis that the decline was caused by
migration to Argentina, where large-scale commercial harvesting operations
claimed over half a million animals. Thus, our study not only provides baseline
data for conservation management but also reveals the potential for genetic
studies to shed light upon long-standing questions pertaining to the history and
fate of natural populations.
PMID- 27493783
TI - Force and torque on spherical particles in micro-channel flows using
computational fluid dynamics.
AB - To delineate the influence of hemodynamic force on cell adhesion processes, model
in vitro fluidic assays that mimic physiological conditions are commonly
employed. Herein, we offer a framework for solution of the three-dimensional
Navier-Stokes equations using computational fluid dynamics (CFD) to estimate the
forces resulting from fluid flow near a plane acting on a sphere that is either
stationary or in free flow, and we compare these results to a widely used
theoretical model that assumes Stokes flow with a constant shear rate. We find
that while the full three-dimensional solutions using a parabolic velocity
profile in CFD simulations yield similar translational velocities to those
predicted by the theoretical method, the CFD approach results in approximately
50% larger rotational velocities over the wall shear stress range of 0.1-5.0
dynes cm(-2). This leads to an approximately 25% difference in force and torque
calculations between the two methods. When compared with experimental
measurements of translational and rotational velocities of microspheres or cells
perfused in microfluidic channels, the CFD simulations yield significantly less
error. We propose that CFD modelling can provide better estimations of
hemodynamic force levels acting on perfused microspheres and cells in flow fields
through microfluidic devices used for cell adhesion dynamics analysis.
PMID- 27493784
TI - A new method for reconstructing brain morphology: applying the brain-neurocranial
spatial relationship in an extant lungfish to a fossil endocast.
AB - Lungfish first appeared in the geological record over 410 million years ago and
are the closest living group of fish to the tetrapods. Palaeoneurological
investigations into the group show that unlike numerous other fishes-but more
similar to those in tetrapods-lungfish appear to have had a close fit between the
brain and the cranial cavity that housed it. As such, researchers can use the
endocast of fossil taxa (an internal cast of the cranial cavity) both as a source
of morphological data but also to aid in developing functional and phylogenetic
implications about the group. Using fossil endocast data from a three-dimensional
preserved Late Devonian lungfish from the Gogo Formation, Rhinodipterus, and the
brain-neurocranial relationship in the extant Australian lungfish, Neoceratodus,
we herein present the first virtually reconstructed brain of a fossil lungfish.
Computed tomographic data and a newly developed 'brain-warping' method are used
in conjunction with our own distance map software tool to both analyse and
present the data. The brain reconstruction is adequate, but we envisage that its
accuracy and wider application in other taxonomic groups will grow with
increasing availability of tomographic datasets.
PMID- 27493786
TI - Shared songs are of lower performance in the dark-eyed junco.
AB - Social learning enables the adjustment of behaviour to complex social and
ecological tasks, and underlies cultural traditions. Understanding when animals
use social learning versus other forms of behavioural development can help
explain the dynamics of animal culture. The dark-eyed junco (Junco hyemalis) is a
songbird with weak cultural song traditions because, in addition to learning
songs socially, male juncos also invent or improvise novel songs. We compared
songs shared by multiple males (i.e. socially learned) with songs recorded from
only one male in the population (many of which should be novel) to gain insight
into the advantages of social learning versus invention or improvisation. Song
types shared by multiple males were on average of lower performance, on aspects
of vocal performance that have been implicated in agonistic communication in
several species. This was not explained by cultural selection among socially
learned songs (e.g. selective learning) because, for shared song types, song
performance did not predict how many males shared them. We discuss why social
learning does not maximize song performance in juncos, and suggest that some
songbirds may add novel songs to culturally inherited repertoires as a means to
acquire higher-quality signals.
PMID- 27493785
TI - Force per cross-sectional area from molecules to muscles: a general property of
biological motors.
AB - We propose to formally extend the notion of specific tension, i.e. force per
cross-sectional area-classically used for muscles, to quantify forces in
molecular motors exerting various biological functions. In doing so, we review
and compare the maximum tensions exerted by about 265 biological motors operated
by about 150 species of different taxonomic groups. The motors considered range
from single molecules and motile appendages of microorganisms to whole muscles of
large animals. We show that specific tensions exerted by molecular and non
molecular motors follow similar statistical distributions, with in particular,
similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the
cell or body from which the motors are extracted, their specific tensions vary as
M(alpha) with alpha not significantly different from zero. The typical specific
tension found in most motors is about 200 kPa, which generalizes to individual
molecular motors and microorganisms a classical property of macroscopic muscles.
We propose a basic order-of-magnitude interpretation of this result.
PMID- 27493787
TI - Effect of vitamin K2 on the anticoagulant activity of warfarin during the
perioperative period of catheter ablation: Population analysis of retrospective
clinical data.
AB - BACKGROUND: Catheter ablation is a non-medication therapy for atrial
fibrillation, and during the procedure, warfarin is withdrawn in the preoperative
period to prevent the risk of bleeding. In case of emergency, vitamin K2 can be
intravenously administered to antagonize the anticoagulant activity of warfarin.
The aims of this study were to conduct population pharmacokinetic/pharmacodynamic
modeling for retrospective clinical data and to investigate the effect of vitamin
K2 on the anticoagulant activity of warfarin in the perioperative period of
catheter ablation. METHODS: A total of 579 international normalized ratio (INR)
values of prothrombin time from 100 patients were analyzed using the nonlinear
mixed-effects modeling program NONMEM. A 1-compartment model was adapted to the
pharmacokinetics of warfarin and vitamin K2, and the indirect response model was
used to investigate the relationship between plasma concentration and the
pharmacodynamic response of warfarin and vitamin K2. Since no plasma
concentration data for warfarin and vitamin K2 were available, 3 literally
available pharmacokinetic parameters were used to simultaneously estimate 1
pharmacokinetic parameter and 5 pharmacodynamic parameters. RESULTS: The
population parameters obtained not only successfully explained the observed INR
values, but also indicated an increase in sensitivity to warfarin in patients
with reduced renal function. Simulations using these parameters indicated that
vitamin K2 administration of more than 20 mg caused a slight dose-dependent
decrease in INR on the day of catheter ablation and a delayed INR elevation after
warfarin re-initiation. CONCLUSIONS: A pharmacokinetic/pharmacodynamic model was
successfully built to explain the retrospective INR data during catheter
ablation. Simulation studies suggest that vitamin K2 should be administered with
care and that more than 20 mg is unnecessary in the preoperative period of
catheter ablation.
PMID- 27493788
TI - Paradoxical reactions under TNF-alpha blocking agents and other biological agents
given for chronic immune-mediated diseases: an analytical and comprehensive
overview.
AB - Paradoxical adverse events (PAEs) have been reported during biological treatment
for chronic immune-mediated diseases. PAEs are defined as the occurrence during
biological agent therapy of a pathological condition that usually responds to
this class of drug. A wide range of PAEs have been reported including
dermatological, intestinal and ophthalmic conditions, mainly with antitumour
necrosis factor alpha (TNF-alpha) agents. True PAEs include psoriasis, Crohn's
disease and hidradenitis suppurativa. Other PAEs may be qualified as borderline
and include uveitis, scleritis, sarcoidosis and other granulomatous diseases
(granuloma annulare, interstitial granulomatous dermatitis), vasculitis, vitiligo
and alopecia areata. Proposed hypotheses to explain these PAEs include an
imbalance in cytokine production, the differential immunological properties
between the monoclonal antibodies and TNF-alpha soluble receptor, an unopposed
type I interferon production and a shift towards a Th1/Th2 profile. Data from
registries suggest that the risk for paradoxical psoriasis is low and non
significant. We discuss management of these PAEs, which depends on the type and
severity of the adverse events, pre-existing treated conditions and the
possibility of alternative therapeutic options for the underlying disease.
Paradoxical adverse events are not restricted to anti-TNF-alpha agents and close
surveillance of new available biological drugs (anti-interleukin-17/23, anti
integrin) is warranted in order to detect the occurrence of new or as yet
undescribed events.
PMID- 27493789
TI - Educational needs and preferences of young European clinicians and physician
researchers working in the field of rheumatology.
AB - OBJECTIVES: To understand the educational needs and preferences of young
clinicians and physician researchers in the field of rheumatology in Europe.
METHODS: An international online survey was performed as a joint venture of ESCET
and EMEUNET. The survey assessed the acceptance of and the access to the current
European League Against Rheumatism (EULAR) educational portfolio, as well as the
unmet educational needs and learning preferences among individuals below the age
of 40 years working in rheumatology in Europe. RESULTS: Among 568 European
clinicians and physician researchers, 65% indicated that the existing EULAR
educational portfolio adequately covers their educational needs. Within the EULAR
portfolio, the online course on rheumatic diseases and the postgraduate course
were the most appreciated. Participants were very much in favour of new
educational courses on imaging techniques, and 63% of participants indicated a
particular interest in musculoskeletal ultrasound. A strong interest in refresher
(60%) and general review (55%) courses was observed. Lack of funding was
considered the major obstacle to participating in existing EULAR programmes.
Finally, participants showed diverse preferences regarding learning modalities
with common interests in live courses and conferences. CONCLUSIONS: EULAR's
training opportunities are well appreciated among young clinicians and physician
researchers in rheumatology. The results from this survey will help to develop
EULAR's future educational portfolio.
PMID- 27493790
TI - Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or
established rheumatoid arthritis.
AB - INTRODUCTION: Tofacitinib is an oral Janus kinase inhibitor for the treatment of
rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to
inhibit structural damage, reduce clinical signs and symptoms of RA, and improve
physical functioning over 24 months in methotrexate (MTX)-naive adult patients
with RA. In this post hoc analysis, we compared efficacy and safety of
tofacitinib in patients with early (disease duration <1 year) versus established
(>=1 year) RA. METHODS: MTX-naive patients >=18 years with active RA received
tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24
month Phase 3 trial. RESULTS: Of 956 patients (tofacitinib 5 mg two times a day,
n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA.
Baseline disease activity and functional disability were similar in both groups;
radiographic damage was greater in patients with established RA. At month 24,
clinical response rates were significantly greater in patients with early versus
established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib
doses had greater effects on clinical, functional and radiographic improvements
at 1 and 2 years compared with MTX, independent of disease duration. No new
safety signals were observed. CONCLUSIONS: Treatment response was generally
similar in early and established RA; significantly greater improvements were
observed at month 24 with tofacitinib 5 mg two times a day in early versus
established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater
efficacy versus MTX irrespective of disease duration. No difference in safety
profiles was observed between patients with early or established RA. TRIAL
REGISTRATION NUMBER: NCT01039688; Results.
PMID- 27493791
TI - Long-term efficiency of infliximab in patients with ankylosing spondylitis: real
life data confirm the potential for dose reduction.
AB - OBJECTIVE: To analyse the treatment outcome of patients with ankylosing
spondylitis (AS) in the European AS infliximab cohort (EASIC) study after a total
period of 8 years with specific focus on dosage and the duration of intervals
between infliximab infusions. METHODS: EASIC included patients with AS who had
received infliximab for 2 years as part of the ASSERT trial. After that period,
rheumatologists were free to change the dose or the intervals of infliximab.
Clinical data were status at baseline, end of ASSERT and for a total of 8 years
of follow-up. RESULTS: Of the initially 71 patients with AS from EASIC, 55
patients (77.5%) had completed the 8th year of anti-tumour necrosis factor (TNF)
treatment. Of those, 48 patients (87.3%) still continued on infliximab. The mean
infusion interval increased slightly from 6 to 7.1+/-1.5 weeks, while 45.8%
patients had increased the intervals up to a maximum of 12 weeks. The mean
infliximab dose remained stable over time, with a minimum of 3.1 mg/kg and a
maximum of 6.4 mg/kg. In patients receiving <5 mg/kg infliximab, the mean
infusion interval increased to 7.0+/-1.2 weeks. In total, the mean cumulative
dose per patient and per year decreased from 3566.30 to 2973.60 mg. CONCLUSIONS:
We could observe that over a follow-up of 8 years of treatment with infliximab,
>85% patients still remained on the same treatment, without any major safety
events. Furthermore, both the infusion intervals and also the mean infliximab
dose were modestly reduced in >=70% of the patients without the loss of clinical
efficiency.
PMID- 27493792
TI - Fatigue in primary Sjogren's syndrome is associated with lower levels of
proinflammatory cytokines.
AB - OBJECTIVES: This article reports relationships between serum cytokine levels and
patient-reported levels of fatigue, in the chronic immunological condition
primary Sjogren's syndrome (pSS). METHODS: Blood levels of 24 cytokines were
measured in 159 patients with pSS from the United Kingdom Primary Sjogren's
Syndrome Registry and 28 healthy non-fatigued controls. Differences between
cytokines in cases and controls were evaluated using Wilcoxon test. Patient
reported scores for fatigue were evaluated, classified according to severity and
compared with cytokine levels using analysis of variance. Logistic regression was
used to determine the most important predictors of fatigue levels. RESULTS: 14
cytokines were significantly higher in patients with pSS (n=159) compared to non
fatigued healthy controls (n=28). While serum levels were elevated in patients
with pSS compared to healthy controls, unexpectedly, the levels of 4
proinflammatory cytokines-interferon-gamma-induced protein-10 (IP-10) (p=0.019),
tumour necrosis factor-alpha (p=0.046), lymphotoxin-alpha (p=0.034) and
interferon-gamma (IFN-gamma) (p=0.022)-were inversely related to patient-reported
levels of fatigue. A regression model predicting fatigue levels in pSS based on
cytokine levels, disease-specific and clinical parameters, as well as anxiety,
pain and depression, revealed IP-10, IFN-gamma (both inversely), pain and
depression (both positively) as the most important predictors of fatigue. This
model correctly predicts fatigue levels with reasonable (67%) accuracy.
CONCLUSIONS: Cytokines, pain and depression appear to be the most powerful
predictors of fatigue in pSS. Our data challenge the notion that proinflammatory
cytokines directly mediate fatigue in chronic immunological conditions. Instead,
we hypothesise that mechanisms regulating inflammatory responses may be
important.
PMID- 27493793
TI - The Utility of Routine Ultrasound Imaging after Elective Transplant Ureteric
Stent Removal.
AB - Background. Ureteric stent insertion during kidney transplantation reduces the
incidence of major urological complications (MUCs). We evaluated whether routine
poststent removal graft ultrasonography (PSRGU) was useful in detecting MUCs
before they became clinically or biochemically apparent. Methods. A retrospective
analysis was undertaken of clinical outcomes following elective stent removals
from adult single renal transplant recipients (sRTRs) at our centre between 1
January 2011 and 31 December 2013. Results. Elective stent removal was performed
for 338 sRTRs. Of these patients, 222 had routine PSRGU (median (IQR) days after
stent removal = 18 (11-31)), 79 had urgent PSRGU due to clinical or biochemical
indications, 12 had CT imaging, and 25 had no further renal imaging. Of the 222
sRTRs who underwent routine PSRGU, 210 (94.6%) had no change of management, three
(1.4%) required repeat imaging only, and eight patients (3.6%) had incidental
(nonureteric) findings. One patient (0.5%) had nephrostomy insertion as a result
of routine PSRGU findings, but no ureteric stenosis was identified. Of 79
patients having urgent PSRGU after elective stent removal, three patients
required transplant ureteric reimplantation. Conclusions. This analysis found no
evidence that routine PSRGU at two to three weeks after elective stent removal
provides any added value beyond standard clinical and biochemical monitoring.
PMID- 27493795
TI - Comparison of Perioperative Ranibizumab Injections for Diabetic Macular Edema in
Patients Undergoing Cataract Surgery.
AB - Purpose. To compare the efficacy of perioperative ranibizumab injections on
diabetic macular edema (DME) in patients undergoing cataract surgery. Methods.
This study included 59 eyes of 59 patients. All patients had advanced cataract
with DME and underwent an uneventful phacoemulsification surgery. There were 3
subgroups. The first group received intravitreal ranibizumab injection 2 weeks
preoperatively, the second group received intraoperatively, and the third group
received 2 weeks postoperatively. Follow-up examinations were performed at 1 week
as well as at 1 and 3 months. Results. Baseline visual acuity showed a
significant increase in all groups at 1 month. In group 1, compared to baseline
value, foveal thickness (FT) increased significantly at 1 month and showed a
significant decrease up to month 3. In group 2, FT increased at month 1 and this
continued up to month 3. In group 3, FT increased at month 1 and was almost
stable up to month 3. There were not any significant differences for visual
acuity and FT between the groups. Conclusions. Although intrapostoperative
ranibizumab injection for DME seems to be more effective than preoperative
injections in patients undergoing cataract surgery, the treatment still needs to
be continued following surgery.
PMID- 27493794
TI - An Update on the Ophthalmologic Features in the Phakomatoses.
AB - Neurofibromatosis type 1, tuberous sclerosis complex, and Von Hippel-Lindau
disease, historically classified as the phakomatoses, are hereditary multisystem
disorders characterized by the presence of hamartoma, which carry the risk of
malignant transformation. The alteration of tumor suppressor genes seems to be at
the basis of their pathophysiogenetic mechanism. Lisch and choroidal nodules in
neurofibromatosis type 1, retinal astrocytomas in tuberous sclerosis complex, and
retinal capillary hemangioma in Von Hippel-Lindau disease are the principal
ophthalmic hamartomatous manifestations. The advent of novel imaging techniques
such as near infrared reflectance and optical coherence tomography has provided
unprecedented insight on the choroidal and retinal features of these diseases.
These methods have improved early diagnosis and the ongoing surveillance in these
conditions. Among an array of treatment modalities, antivascular endothelial
growth factor therapy has been used in the management of retinal hamartomas but
results have been varied. This review is an update on the pathophysiogenetic
mechanisms, ophthalmic manifestations, and novel treatment strategies in the
phakomatoses with emphasis on the role of imaging techniques.
PMID- 27493796
TI - Optic Disc, Macula, and Retinal Nerve Fiber Layer Measurements Obtained by OCT in
Thyroid-Associated Ophthalmopathy.
AB - Aim. To compare the measurements of retinal nerve fiber layer (RNFL), macula and
optic disc parameters obtained by optical coherence tomography (OCT), and
intraocular pressure (IOP) between the patients with thyroid-associated
ophthalmopathy (TAO) and healthy controls. Methods. One hundred and thirty-two
eyes of 66 patients with TAO and 72 eyes of 36 healthy controls were included in
the study. Proptosis level was determined by Hertel exophthalmometer. Optic disc,
peripapillary retinal nerve fiber layer, and macula parameters were measured by
OCT. All measurements of the patients were compared with those of age- and sex
matched healthy controls. Results. No statistically significant difference was
found between the patients with TAO and control group in terms of demographic
characteristics (P > 0.05). Exophthalmometer measurements and IOP were higher in
TAO group (P < 0.05). Mean macula thicknesses in TAO and control groups were
239.3 +/- 29.8 MUm and 246.6 +/- 31.8 MUm, respectively, and the difference
between the groups was statistically significant (P = 0.000). TAO group had
thinner inferior RNFL thickness and macular thicknesses (superior, inferior,
temporal, and nasal) and higher disc area and C/D ratio when compared with the
control group (P < 0.05). Conclusion. IOP, disc area, and C/D area ratio were
higher in the patients with TAO and the thicknesses of macula and inferior RNFL
were thinner when compared with healthy controls. This trial is registered with
registration number at clinicaltrials.gov NCT02766660.
PMID- 27493797
TI - Community Engaged Lifestyle Modification Research: Engaging Diabetic and
Prediabetic African American Women in Community-Based Interventions.
AB - Purpose. The I Am Woman (IAW) Program is a community-based, culturally
responsive, and gender-specific nutrition, obesity, and diabetes educational
prevention program designed for African American women (AAW). Chronic nutrition
related health conditions such as excess body weight, diabetes mellitus,
cardiovascular disease, and some forms of cancer are common among many African
American women. Methods. IAW engaged AAW at risk for such deleterious health
conditions by developing a health education intervention that aimed to support
weight loss and management, improve knowledge about healthy lifestyle behavioral
choices, and facilitate increased access to comprehensive healthcare. This
Community Health Worker- (CHW-) led program enrolled 79 AAW aged 18 and older in
a 7-week group health education intervention. Results. Following the
intervention, results indicated that participants had greater knowledge about
nutrition and health, strategies for prevention and management of obesity and
diabetes, increased engagement in exercise and fitness activities, and decreased
blood pressure, weight, body, and mass index. Cholesterol levels remained
relatively unchanged. Additionally, AAW visited a primary care doctor more
frequently and indicated greater interest in addressing their health concerns.
Conclusion. This model of prevention appears to be a promising approach for
increasing awareness about ways to improve the health and well-being of AAW.
PMID- 27493798
TI - Liver Enzymes Abnormalities among Highly Active Antiretroviral Therapy
Experienced and HAART Naive HIV-1 Infected Patients at Debre Tabor Hospital,
North West Ethiopia: A Comparative Cross-Sectional Study.
AB - Liver disease has emerged as the most common non-AIDS-related cause of death in
HIV patients. However, there is limited data regarding this condition including
our setting in Ethiopia. Hence, liver enzyme abnormalities among highly active
antiretroviral therapy (HAART) experienced and HAART naive patients were assessed
in this study. A total of 164 HAART experienced and 164 HAART naive patients were
studied. Blood specimen was collected to determine alanine aminotransferase (ALT)
and aspartate aminotransferase (AST), CD4 count, and viral hepatitis. The
prevalence of liver enzyme abnormality was 20.1% and 22.0% among HAART
experienced and HAART naive patients, respectively. The HAART experienced
patients had higher mean ALT than HAART naive patients (P = 0.002). Viral
hepatitis (AOR = 6.02; 95% CI = 1.87-19.39), opportunistic infections (AOR =
2.91; 95% CI = 1.04-8.19), current CD4 count <200 cells/mm(3) (AOR = 2.16; 95% CI
= 1.06-4.39), and male sex (AOR = 1.83; 95% CI = 1.001-3.33) were associated with
elevated ALT and/or AST. In conclusion, liver enzyme abnormalities were high in
both HAART experienced and HAART naive HIV-1 infected patients. Hence, monitoring
and management of liver enzyme abnormalities in HIV-1 infected patients are
important in our setting.
PMID- 27493799
TI - Determinants of Deescalation Failure in Critically Ill Patients with Sepsis: A
Prospective Cohort Study.
AB - Introduction. Deescalation refers to either discontinuation or a step-down of
antimicrobials. Despite strong recommendations in the Surviving Sepsis Guidelines
(2012) to deescalate, actual practices can vary. Our objective was to identify
variables that are associated with deescalation failure. Methods. In this
prospective study of patients with sepsis/septic shock, patients were categorized
into 4 groups based on antibiotic administration: no change in antibiotics,
deescalation, escalation (where antibiotics were changed to those with a broader
spectrum of antimicrobial coverage), or mixed changes (where both escalation to a
broader spectrum of coverage and discontinuation of antibiotics were carried
out). Results. 395 patients were studied; mean APACHE II score was 24 +/- 7.8.
Antimicrobial deescalation occurred in 189 (48%) patients; no changes were made
in 156 (39%) patients. On multivariate regression analysis, failure to deescalate
was significantly predicted by hematologic malignancy OR 3.3 (95% CI 1.4-7.4) p <
0.004, fungal sepsis OR 2.7 (95% CI 1.2-5.8) p = 0.011, multidrug resistance OR
2.9 (95% CI 1.4-6.0) p = 0.003, baseline serum procalcitonin OR 1.01 (95% CI
1.003-1.016) p = 0.002, and SAPS II scores OR 1.01 (95% CI 1.004-1.02) p = 0.006.
Conclusions. Current deescalation practices reflect physician reluctance when
dealing with complicated, sicker patients or with drug-resistance or fungal
sepsis. Integrating an antibiotic stewardship program may increase physician
confidence and provide support towards increasing deescalation rates.
PMID- 27493800
TI - The Use of Xpert MTB/Rif for Active Case Finding among TB Contacts in North West
Province, South Africa.
AB - Introduction. Tuberculosis is a major cause of morbidity and mortality especially
in high HIV burden settings. Active case finding is one strategy to potentially
reduce TB disease burden. Xpert MTB/Rif has recently been recommended for
diagnosis of TB. Methods. Pragmatic randomized trial to compare diagnosis rate
and turnaround time for laboratory testing for Xpert MTB/Rif with TB microscopy
and culture in household contacts of patients recently diagnosed with TB.
Results. 2464 household contacts enrolled into the study from 768 active TB index
cases. 1068 (44%) were unable to give sputum, but 24 of these were already on TB
treatment. 863 (53%) participants sputum samples were tested with smear and
culture and 2.7% (23/863; CI: 1.62-3.78) were diagnosed with active TB. Xpert
MTB/Rif was used in 515 (21%) participants; active TB was diagnosed in 1.6%
(8/515; CI: 0.52-2.68). Discussion and Conclusions. Additional 31 cases were
diagnosed with contact tracing of household members. When Xpert MTB/Rif is
compared with culture, there is no significant difference in diagnostic yield.
PMID- 27493801
TI - Prevalence of Hypercalcaemia in a Renal Transplant Population: A Single Centre
Study.
AB - Introduction. Postrenal transplant bone disease is a significant problem. Factors
influencing postrenal transplant bone status include high dose acute and low dose
long-term steroid use, persistent hypercalcaemia, and graft failure. In this
study, we aimed to determine the prevalence of hypercalcaemia and to evaluate the
risk factors for postrenal transplant hypercalcaemia in long-term renal
transplant patients at our centre. Methods. This is a biochemical audit in which
we studied renal transplant recipients from the Central Northern Adelaide Renal
Transplant Services, South Australia. Inclusion criteria include kidney
transplant patients with functioning graft since 1971 and at least 3 months after
transplantation at the time of analysis. Hypercalcaemia was defined as
persistently elevated serum corrected calcium greater than or equal to 2.56
mmol/L for three consecutive months. Results. 679 renal transplant recipients
with a functioning graft were studied and 101 were hypercalcaemic between March
2011 and June 2011 (15%). 60% of the hypercalcaemic patients were male and 40%
were female, with chronic glomerulonephritis (39%) being the commonest cause of
their end stage kidney disease (ESKD). Prevalence was similar in those that had
haemodialysis and peritoneal dialysis pretransplantation. Hypercalcaemia in the
renal transplant population was not secondary to suboptimal allograft function
but secondary to pretransplantation hyperparathyroidism with persistent high
parathyroid hormone (PTH) levels after transplantation. Conclusion. There is a
high prevalence of hypercalcaemia (15%) in renal transplant recipients. The
predominant cause for hypercalcaemia is pretransplantation hyperparathyroidism.
The magnitude of pretransplantation hyperparathyroidism is the major determinant
for long-term parathyroid function rather than graft function or
pretransplantation duration on dialysis or mode of dialysis.
PMID- 27493802
TI - Urinary Markers of Tubular Injury in HIV-Infected Patients.
AB - Renal disease is a common complication of HIV-infected patients, associated with
increased risk of cardiovascular events, progression to AIDS, AIDS-defining
illness, and mortality. Early and accurate identification of renal disease is
therefore crucial to improve patient outcomes. The use of serum creatinine, along
with proteinuria, to detect renal involvement is essentially to screen for
markers of glomerular disease and may not be effective in detecting earlier
stages of renal injury. Therefore, more sensitive and specific markers are needed
in order to early identify HIV-infected patients at risk of renal disease. This
review article summarizes some new and important urinary markers of tubular
injury in HIV-infected patients and their clinical usefulness in the renal safety
follow-up of TDF-treated patients.
PMID- 27493803
TI - Morphology and Functional Anatomy of the Recurrent Laryngeal Nerve with
Extralaryngeal Terminal Bifurcation.
AB - Anatomical variations of the recurrent laryngeal nerve (RLN), such as an
extralaryngeal terminal bifurcation (ETB), threaten the safety of thyroid
surgery. Besides the morphology of the nerve branches, intraoperative evaluation
of their functional anatomy may be useful to preserve motor activity. We exposed
67 RLNs in 36 patients. The main trunk, bifurcation point, and terminal branches
of bifid nerves were macroscopically determined and exposed during thyroid
surgery. The functional anatomy of the nerve branches was evaluated by
intraoperative nerve monitoring (IONM). Forty-six RLNs with an ETB were
intraoperatively exposed. The bifurcation point was located along the
prearterial, arterial, and postarterial segments in 11%, 39%, and 50% of bifid
RLNs, respectively. Motor activity was determined in all anterior branches. The
functional anatomy of terminal branches detected motor activity in 4 (8.7%)
posterior branches of 46 bifid RLNs. The motor activity in posterior branches
created a wave amplitude at 25-69% of that in the corresponding anterior
branches. The functional anatomy of bifid RLNs demonstrated that anterior
branches always contained motor fibres while posterior branches seldom contained
motor fibres. The motor activity of the posterior branch was weaker than that of
the anterior branch. IONM may help to differentiate between motor and sensory
functions of nerve branches. The morphology and functional anatomy of all nerve
branches must be preserved to ensure a safer surgery.
PMID- 27493804
TI - High Dose Rate Brachytherapy as a Treatment Option in Endobronchial Tumors.
AB - Purpose. To report our experience with high dose rate endobronchial brachytherapy
(HDR-EBBT) and to assess its efficacy and tolerability with possibility of its
use in selected cases with curative intent. Method. Retrospective review of
patients with endobronchial tumors treated at our institution in 2007-2013 with
HDR-EBBT. Subjective response and treatment related toxicity were extracted from
patients' records. Clinical response was evaluated by chest CT +/- bronchoscopy 2
3 months after treatment. Local control (LC) and overall survival (OS) were
analyzed. Results. Overall 23 patients were identified. Ten patients were treated
with curative intent, in 8 of them HDR-EBBT was combined with external beam
radiotherapy. Short term palliation was as follows: dyspnea (13/15), cough
(12/14), and hemoptysis (3/3). Seventeen patients were evaluated, of whom 9 (53%)
showed complete response. Four patients developed local failure (only 1 of them
treated with curative intent) and were salvaged with HDR-EBBT (n = 1),
chemotherapy (n = 2), and laser (n = 1). Among patients treated with curative
intent, the 2-year LC and OS were 89% and 67%, respectively, and 2 out of 4
deaths were cancer-related. Late toxicity included bronchial stenosis (n = 1).
Only 1 patient had fatal hemoptysis and postmortem examination indicated local
recurrence. Conclusion. HDR-EBBT is promising treatment with tolerable
complication if used in properly selected patients.
PMID- 27493805
TI - Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time
Window in Rats.
AB - Although the importance of DNA methylation-dependent gene expression to neuronal
plasticity is well established, the dynamics of methylation and demethylation
during the induction and expression of synaptic plasticity have not been
explored. Here, we combined electrophysiological, pharmacological, molecular, and
immunohistochemical approaches to examine the contribution of DNA methylation and
the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) to synaptic
plasticity. We found that, at twenty minutes after theta burst stimulation (TBS),
the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA) impaired hippocampal
long-term potentiation (LTP). Surprisingly, after two hours of TBS, when LTP had
become a transcription-dependent process, 5AZA treatment had no effect. By
comparing these results to those in naive slices, we found that, at two hours
after TBS, an intergenic region of the RLN gene was hypomethylated and that the
phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation
of residue S421 was increased. As expected, 5AZA affected only the methylation of
the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary,
our data suggest that tetanic stimulation induces critical changes in synaptic
plasticity that affects both DNA methylation and the phosphorylation of MeCP2.
These data also suggest that early alterations in DNA methylation are sufficient
to impair the full expression of LTP.
PMID- 27493806
TI - Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron
Polarity.
AB - The axon initial segment (AIS) is a specialized structure in neurons that resides
in between axonal and somatodendritic domains. The localization of the AIS in
neurons is ideal for its two major functions: it serves as the site of action
potential firing and helps to maintain neuron polarity. It has become
increasingly clear that the AIS cytoskeleton is fundamental to AIS functions. In
this review, we discuss current understanding of the AIS cytoskeleton with
particular interest in its unique architecture and role in maintenance of neuron
polarity. The AIS cytoskeleton is divided into two parts, submembrane and
cytoplasmic, based on localization, function, and molecular composition. Recent
studies using electron and subdiffraction fluorescence microscopy indicate that
submembrane cytoskeletal components (ankyrin G, betaIV-spectrin, and actin
filaments) form a sophisticated network in the AIS that is conceptually similar
to the polygonal/triangular network of erythrocytes, with some important
differences. Components of the AIS cytoplasmic cytoskeleton (microtubules, actin
filaments, and neurofilaments) reside deeper within the AIS shaft and display
structural features distinct from other neuronal domains. We discuss how the AIS
submembrane and cytoplasmic cytoskeletons contribute to different aspects of AIS
polarity function and highlight recent advances in understanding their AIS
cytoskeletal assembly and stability.
PMID- 27493807
TI - Emotion Dysregulation and Inflammation in African-American Women with Type 2
Diabetes.
AB - C-reactive protein (CRP), a marker of systemic inflammation, has been associated
with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD).
Emotion dysregulation is a transdiagnostic risk factor for many psychological
disorders associated with chronic inflammatory state. The objective of this study
was to determine whether inflammation is associated with emotion dysregulation in
women with type 2 diabetes mellitus (T2DM). We examined associations between
trauma exposure, MDD, PTSD, emotion dysregulation, and CRP among 40 African
American women with T2DM recruited from an urban hospital. Emotion dysregulation
was measured using the Difficulties in Emotion Regulation Scale. PTSD and MDD
were measured with structured clinical interviews. Child abuse and lifetime
trauma load were also assessed. Analyses showed that both emotion dysregulation
and current MDD were significantly associated with higher levels of CRP (p <
0.01). Current PTSD was not significantly related to CRP. In a regression model,
emotion dysregulation was significantly associated with higher CRP (p < 0.001)
independent of body mass index, trauma exposure, and MDD diagnosis. These
findings suggest that emotion dysregulation may be an important risk factor for
chronic inflammation beyond already known risk factors among women with T2DM,
though a causal relationship cannot be determined from this study.
PMID- 27493808
TI - Innovative trends and perspectives for erectile dysfunction treatment: A
systematic review.
AB - OBJECTIVE: To review contemporary knowledge concerning the innovative trends and
perspectives in the treatment of erectile dysfunction (ED). METHODS: Medline was
reviewed for English-language journal articles between January 2000 and March
2016, using the terms 'erectile dysfunction treatments', 'new trends' and
'perspectives'. In all, 114 original articles and 16 review articles were found
to be relevant. Of the 76 cited papers that met the inclusion criteria, 51 papers
had level of evidence of 1a-2b, whilst 25 had level of evidence of 3-4. Criteria
included all pertinent review articles, randomised controlled trials with tight
methodological design, cohort studies, and retrospective analyses. We also
manually reviewed references from selected articles. RESULTS: Several interesting
studies have addressed novel phosphodiesterase type 5 inhibitors (PDE5Is),
orodispersible tablets, their recent chronic use, and combination with other
agents. A few controlled studies have addressed herbal medicine as a sole or
additional treatment for ED. Experimental studies and exciting review papers have
addressed stem cells as novel players in the field of ED treatment. Other recent
articles have revised the current status of low-intensity extracorporeal
shockwave therapy in the field of ED. A few articles without long-term data have
addressed new technologies that included: external penile support devices, penile
vibrators, tissue engineering, nanotechnology, and endovascular tools for ED
treatment. CONCLUSIONS: The current treatment of ED is still far from ideal. We
expect to see new drugs and technologies that may revolutionise ED treatment,
especially in complex cases.
PMID- 27493809
TI - Internal versus external ureteric stents for uretero-ileal anastomosis after
laparoscopic radical cystectomy with orthotopic neobladder: A prospective
comparative study.
AB - OBJECTIVE: To prospectively compare the use of external ureteric stents with
internal JJ stenting of the uretero-ileal anastomosis in patients undergoing
laparoscopic radical cystectomy (LRC) with a Y-shaped ileal orthotopic neobladder
(ON). PATIENTS AND METHODS: The study included 69 patients undergoing LRC with
ON. Patients were grouped according to the type of uretero-ileal stents used. An
external ureteric stent was used in Group A (33 patients) and a JJ stent was used
in Group B (36). We prospectively compared the duration of hospital stay, the
incidence of short- and intermediate-term complications in the two study groups.
RESULTS: The mean (SD) follow-up periods were 29.18 (3.94) and 28.19 (3.37)
months for patients in Groups A and B, respectively. Perioperative patient
characteristics were comparable in the two study groups. The use of JJ stenting
was associated with a shorter hospital stay compared with external stenting, at a
mean (SD) of 14.63 (3.74) and 6.8 (3.03) days in Groups A and B, respectively (P
< 0.001). The incidence of urinary leakage was comparable in the two study
groups, at 6.1% in Group A vs 8.3% in Group B (P = 1.0). Strictures of the
uretero-ileal anastomosis occurred in two patients (6%) in Group A and confirmed
by intravenous urography. All strictures were treated with antegrade JJ fixation.
CONCLUSION: JJ stents could be used as an effective alternative to external
ureteric stents to support the uretero-ileal anastomosis. JJ stenting is
associated with a shorter hospital stay and similar complication rates compared
with external stenting in patients undergoing LRC with ON.
PMID- 27493810
TI - The embedded nipple: An optimal technique for re-implantation of primary
obstructed megaureter in children.
AB - OBJECTIVES: To present a novel ureteric re-implantation technique for primary
obstructed megaureter (POM) that ensures success in the short- and long-term, as
conventional techniques are not ideal for megaureters especially in children,
with ureteric stenosis and reflux being common complications after re
implantation. PATIENTS AND METHODS: Between 2009 and 2012, 22 paediatric patients
with POM were enrolled. We performed a new technique for re-implantation of these
ureters to ensure minimal incidence of ureteric strictures and easy subsequent
endoscopic access. We performed follow-up voiding cystourethrography (VCUG) at 6
months postoperatively. RESULTS: The cohort comprised 14 boys and eight girls,
with a median age of 22 months. Six patients underwent bilateral re-implantation.
The mean (range) duration of indwelling ureteric catheterisation was 7.8 (4-14)
days. There were no complications in the perioperative and postoperative periods.
There was no reflux on follow-up VCUG in any of the patients. One patient
developed Grade I reflux after 1 year and presented with a urinary tract
infection. Diagnostic cystoscopy was performed in 13 patients showing that the
nipple was directed similarly to the native ureteric orifice. CONCLUSION: The
embedded-nipple technique for re-implantation of POM guarantees successful
results and permits easy subsequent ureteroscopic access when needed.
PMID- 27493811
TI - Paediatric Nonfunctioning Adrenocortical Carcinoma with Extension up to Right
Side Heart: Cardiac Surgery Approach.
AB - Adrenocortical carcinoma is a rare malignancy. Due to late diagnosis and no
adequate effective adjuvant treatment, prognosis remains poor. Only approximately
30% of these malignancies are confined to the adrenal gland when they are
diagnosed, as these tumors tend to be found years after their genesis. Cardiac
involvement of adrenal carcinoma is very rare. We report a rare case of a 7-year
old female with right adrenal cortical carcinoma, involving the right-side heart.
PMID- 27493812
TI - Propofol Infusion Syndrome in Refractory Status Epilepticus: A Case Report and
Topical Review.
AB - Propofol infusion syndrome (PRIS) is a fatal complication when doses of propofol
administration exceed 4 mg/kg/h for more than 48 hours. Propofol overdosage is
not uncommon in patients with refractory status epilepticus (RSE). We describe a
case of refractory status epilepticus complicated by propofol infusion syndrome
and collect from 5 databases all reports of refractory status epilepticus cases
that were treated by propofol and developed the syndrome and outline whether
refractory status epilepticus treatment with propofol is standardized according
to international recommendations, compare it with alternative medications, and
discuss how this syndrome can be treated and prevented. A total of 21 patients
who developed this syndrome reported arrhythmia in all cases (100%),
rhabdomyolysis in 9 cases (42%), lactic acidosis in 13 cases (62%), renal failure
in 8 cases (38%), lipemia in 7 cases (33%), and elevated hepatic enzymes in 6
cases (28%). 13 patients died (66%). Propofol is still given in a dosage higher
than what is internationally recommended, and new treatment modalities such as
renal replacement therapy, blood exchange, and extracorporeal membrane
oxygenation seem to be promising. In conclusion, propofol should be carefully
titrated, the maximal infusion rate needs to be reassessed, and combination of
different sedative agents may be considered.
PMID- 27493813
TI - Extranodal NK/T Cell Lymphoma Causing Cardiorespiratory Failure.
AB - Extranodal NK/T cell lymphoma is an uncommon malignancy usually involving the
sinonasal area. We report an unusual case of extranodal NK/T cell lymphoma
diagnosed in a 62-year-old Caucasian male who died of progressive
cardiorespiratory failure but had no clinically detectable upper respiratory
system lesions. The initial diagnosis was made cytologically on a sample of
pericardial fluid that contained neoplastic lymphoid cells. These cells were
positive for CD2, cytoplasmic CD3, and Epstein-Barr virus and negative for CD56.
The diagnosis was confirmed at the autopsy, which disclosed lymphoma infiltrates
in the myocardium, lungs, stomach, and pancreas. The death was caused by heart
and lung failure due to uncontrollable arrhythmia and respiratory insufficiency
due to the lymphoma infiltrates. To the best of our knowledge, this is the first
case of extranodal NK/T cell lymphoma presenting with cardiopulmonary failure.
PMID- 27493814
TI - Spontaneous Bilateral Tubal Gestation: A Rare Case Report.
AB - Here a case is presented where the woman after a positive pregnancy test
underwent medical abortion for unwanted pregnancy without ultrasound confirmation
of intrauterine pregnancy. On persistence of symptoms, a second opinion was
procured, when examination and a transvaginal ultrasound scan revealed ruptured
unilateral tubal ectopic pregnancy. However upon subsequent laparotomy
(considering deteriorating hemodynamic status of the patient), intraoperatively
it turned out to be a bilateral tubal ectopic gestation.
PMID- 27493815
TI - Resuscitating the Baby after Shoulder Dystocia.
AB - Background. To propose hypovolemic shock as a possible explanation for the
failure to resuscitate some babies after shoulder dystocia and to suggest a
change in clinical practice. Case Presentation. Two cases are presented in which
severe shoulder dystocia was resolved within five minutes. Both babies were born
without a heartbeat. Despite standard resuscitation by expert neonatologists, no
heartbeat was obtained until volume resuscitation was started, at 25 minutes in
the first case and 11 minutes in the second. After volume resuscitation
circulation was restored, there was profound brain damage and the babies died.
Conclusion. Unsuspected hypovolemic shock may explain some cases of failed
resuscitation after shoulder dystocia. This may require a change in clinical
practice. Rather than immediately clamping the cord after the baby is delivered,
it is proposed that (1) the obstetrician delay cord clamping to allow
autotransfusion of the baby from the placenta and (2) the neonatal resuscitators
give volume much sooner.
PMID- 27493816
TI - A Misguiding Osteoid Osteoma in the Bicipital Tuberosity of the Radius.
AB - Osteoid osteoma is a benign bone tumor that appears most frequently in young
patients. It is more common in males and it concerns mostly the long bones of the
lower limb. A 20-year-old young woman presented to our outpatient department with
pain in her left elbow. The symptoms began four years ago. At first, her symptoms
were attributed to ulnar neuritis, confirmed by nerve conduction studies. In the
following two years, she had undergone two surgical operations for decompression
of the ulnar nerve. As a result, she reported poor results, which forced her to
take frequently anti-inflammatory drugs for some years. When the patient
presented to us, we planned a three-phase bone scan and an elbow MRI, which
revealed the lesion. Based on the image findings of osteoid osteoma, we proceeded
to the surgical removal of the tumor. Since then, the patient is pain-free and
has a full range of motion of the affected elbow. Osteoid osteoma usually mimics
multiple pathologies in the upper limb especially joint disease posing a
challenge for the physician. The diagnosis requires high index of suspicion and a
prompt diagnostic and surgical management.
PMID- 27493817
TI - Morel-Lavallee Lesion of the Knee in a Recreational Frisbee Player.
AB - Traumatic swelling/effusion in the knee region is a relatively common presenting
complaint among athletes and nonathletes. Due to its broad differential
diagnosis, a comprehensive evaluation beginning with history and physical
examination are recommended. Knee joint effusion can be differentiated from other
types of swelling by careful physical examination. Imaging, including plain
radiography, ultrasound, and magnetic resonance imaging (MRI), is preferred
modality. Aspiration of a local fluctuating mass may help with the diagnosis and
management of some of these conditions. We present a case of a 26-year-old
gentleman with superomedial Morel-Lavallee lesion (MLL) of the knee with history
of a fall during a Frisbee game. His MLL was successfully treated with
therapeutic aspiration and compression wrap without further sequelae. MLL is a
rare condition consisting of a closed degloving injury caused by pressure and
shear stress between the subcutaneous tissue and the superficial fascia or bone.
Most commonly, MLL is found over the greater trochanter and sacrum but in rare
cases can occur in other regions of the body. In most cases, concurrent severe
injury mechanisms and concomitant fractures are present. MLL due to sports
injuries are very rare. Therapeutic strategies may vary from compression wraps
and aspiration to surgical evacuation.
PMID- 27493818
TI - INFIX/EXFIX: Massive Open Pelvic Injuries and Review of the Literature.
AB - Introduction. Open pelvic fractures make up 2-5% of all pelvic ring injuries.
Their mortality has been reported to be as high as 50%. During Operation Enduring
Freedom protocols for massive open pelvic injuries lead to the survival of
injuries once thought to be fatal. The INFIX is a subcutaneous anterior fixator
for pelvic stabilization which is stronger than external fixation. The purpose of
this paper is to describe the use of INFIX and modern algorithms for massive open
pelvic injuries. Methods. An IRB approved retrospective review describes 4 cases
in civilian practice with massive open pelvic injuries. We also review the modern
literature on open pelvic injures. Discussion. Key components in the care of
massive open pelvic injuries include hemorrhage control by clamping of the aorta
or REBOA when necessary and fecal/urinary diversion. The INFIX can be used
internally, as a partial INFIX partial EXFIX, or as an EXFIX. Its low profile
allows for easy application of wound vacs and wound care and when subcutaneous
avoids pin tract infections. Conclusion. Massive open pelvic injuries are a
difficult problem. Following modern protocols can help prevent mortality.
PMID- 27493819
TI - Coracoid Process Avulsion Fracture at the Coracoclavicular Ligament Attachment
Site in an Osteoporotic Patient with Acromioclavicular Joint Dislocation.
AB - Coracoid fractures are uncommon, mostly occur at the base or neck of the coracoid
process (CP), and typically present with ipsilateral acromioclavicular joint
(ACJ) dislocation. However, CP avulsion fractures at the coracoclavicular
ligament (CCL) attachment with ACJ dislocation have not been previously reported.
A 59-year-old woman receiving glucocorticoid treatment fell from bed and
complained of pain in her shoulder. Radiographs revealed an ACJ dislocation with
a distal clavicle fracture. Three-dimensional computed tomography (3D-CT)
reconstruction showed a small bone fragment at the medial apex of the CP. She was
treated conservatively and achieved a satisfactory outcome. CP avulsion fractures
at the CCL attachment can occur in osteoporotic patients with ACJ dislocations.
Three-dimensional computed tomography is useful for identifying this fracture
type. CP avulsion fractures should be suspected in patients with ACJ dislocations
and risk factors for osteoporosis or osteopenia.
PMID- 27493820
TI - Granulomatosis with Polyangiitis with Bilateral Facial Palsy and Severe Mixed
Hearing Loss.
AB - Granulomatosis with polyangiitis is autoimmune and rare disease. It affects many
organs, but the most often affected organs are the nose, lungs, and kidneys. It
is part of vasculitis and causes an autoimmune attack by an abnormal type of
circulating antibody termed ANCAs against small blood vessels. Disease concerns
both men and women with a peak age of presentation in the sixth and seven
decades. Typically upper and lower respiratory tract and kidneys are involved.
Otitis externa, otitis media, or mastoiditis rarely occurs in granulomatosis with
polyangiitis. Deafness is the most dangerous aural complication. Histological
examination of biopsy is often not specific. A case of GPA with bilateral otitis
media, bilateral deafness, and bilateral facial palsy with fatal course is
presented.
PMID- 27493821
TI - Generalized Anxiety Disorder and Hypoglycemia Symptoms Improved with Diet
Modification.
AB - Observational evidence suggests that a relationship may exist between high
glycemic index diets and the development of anxiety and depression symptoms;
however, as no interventional studies assessing this relationship in a
psychiatric population have been completed, the possibility of a causal link is
unclear. AB is a 15-year-old female who presented with concerns of generalized
anxiety disorder and hypoglycemia symptoms. Her diet consisted primarily of
refined carbohydrates. The addition of protein, fat, and fiber to her diet
resulted in a substantial decrease in anxiety symptoms as well as a decrease in
the frequency and severity of hypoglycemia symptoms. A brief return to her
previous diet caused a return of her anxiety symptoms, followed by improvement
when she restarted the prescribed diet. This case strengthens the hypothesis that
dietary glycemic index may play a role in the pathogenesis or progression of
mental illnesses such as generalized anxiety disorder and subsequently that
dietary modification as a therapeutic intervention in the treatment of mental
illness warrants further study.
PMID- 27493823
TI - Erratum to "Endobronchial Enigma: A Clinically Rare Presentation of Nocardia
beijingensis in an Immunocompetent Patient".
AB - [This corrects the article DOI: 10.1155/2015/970548.].
PMID- 27493822
TI - Dandy-Walker Malformation Presenting with Psychological Manifestations.
AB - Dandy-Walker malformation, which is a congenital malformation of the cerebellum,
is documented in literature to be associated with psychotic symptoms, obsessive
compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The
pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to
be due to disruption of the corticocerebellar tracts, resulting in what is known
as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker
malformation presenting with psychiatric symptoms. This case highlights the
necessity to be aware of psychiatric manifestations of cerebellar disease as it
has an impact on the diagnosis and treatment.
PMID- 27493824
TI - MRI Findings of Syndrome of Acute Bilateral Symmetrical Basal Ganglia Lesions in
Diabetic Uremia: A Case Report and Literature Review.
AB - The syndrome of acute bilateral basal ganglia lesions is an uncommon clinical
occurrence exhibiting acute onset of movement abnormalities, which can be seen
almost exclusively among patients with chronic renal failure, especially in the
setting of concurrent diabetes mellitus. Symmetrical lesions located in basal
ganglia demonstrated in MRI are typical manifestation of this syndrome. Our study
includes routine MRI examination, MRS, 3D-ASL, and SWI findings, which have been
rarely reported and will contribute to diagnosing more cases about this syndrome.
PMID- 27493825
TI - Giant Cell Arteritis: An Atypical Presentation Diagnosed with the Use of MRI
Imaging.
AB - Giant cell arteritis (GCA) is the most common primary systemic vasculitis in
western countries in individuals over the age of 50. It is typically
characterised by the granulomatous involvement of large and medium sized blood
vessels branching of the aorta with particular tendencies for involving the
extracranial branches of the carotid artery. Generally the diagnosis is
straightforward when characteristic symptoms such as headache, jaw claudication,
or other ischemic complications are present. Atypical presentations of GCA
without "overt" cranial ischemic manifestations have become increasingly
recognised but we report for the first time a case of GCA presenting as mild
upper abdominal pain and generalized weakness in the context of hyponatremia as
the presenting manifestation of vasculitis that was subsequently diagnosed by MRI
scanning. This case adds to the literature and emphasises the importance of MRI
in the evaluation of GCA patients without "classic" cranial ischemic symptoms.
PMID- 27493826
TI - Facilitators and Barriers to Linkage to HIV Care among Female Sex Workers
Receiving HIV Testing Services at a Community-Based Organization in Periurban
Uganda: A Qualitative Study.
AB - Introduction. While four in ten female sex workers (FSWs) in sub-Saharan Africa
are infected with HIV, only a small proportion is enrolled in HIV care. We
explored facilitators and barriers to linkage to HIV care among FSWs receiving
HIV testing services at a community-based organization in periurban Uganda.
Methods. The cross-sectional qualitative study was conducted among 28 HIV
positive FSWs from May to July 2014. Key informant interviews were conducted with
five project staff and eleven peer educators. Data were collected on facilitators
for and barriers to linkage to HIV care and manually analyzed following a
thematic framework approach. Results. Facilitators for linkage to HIV care
included the perceived good quality of health services with same-day results and
immediate initiation of treatment, community peer support systems, individual's
need to remain healthy, and having alternative sources of income. Linkage
barriers included perceived stigma, fear to be seen at outreach HIV clinics, fear
and myths about antiretroviral therapy, lack of time to attend clinic, and
financial constraints. Conclusion. Linkage to HIV care among FSWs is influenced
by good quality friendly services and peer support. HIV service delivery programs
for FSWs should focus on enhancing these and dealing with barriers stemming from
stigma and misinformation.
PMID- 27493827
TI - Cost-Effectiveness and Validity Assessment of Cyscope Microscope, Quantitative
Buffy Coat Microscope, and Rapid Diagnostic Kit for Malaria Diagnosis among
Clinic Attendees in Ibadan, Nigeria.
AB - Background. Unavailability of accurate, rapid, reliable, and cost-effective
malaria diagnostic instruments constitutes major a challenge to malaria
elimination. We validated alternative malaria diagnostic instruments and assessed
their comparative cost-effectiveness. Method. Using a cross-sectional study
design, 502 patients with malaria symptoms at selected health facilities in
Ibadan between January and April 2014 were recruited consecutively. We examined
malaria parasites using Cyscope(r), QBC, and CareStartTM and results were
compared to light microscopy (LM). Validity was determined by assessing
sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV). Costs per hour of use for instruments and turnaround time
were determined. Result. Sensitivity of the instruments was 76.0% (CareStart),
95.0% (Cyscope), and 98.1% (QBC). Specificity was 96.0% (CareStart), 87.3%
(Cyscope), and 85.5% (QBC). PPV were 65.2%, 67.5%, and 84.7%, while NPV were
93.6%, 98.6%, and 99.4% for CareStart, Cyscope, and QBC with Kappa values of 0.75
(CI = 0.68-0.82) for CareStart, 0.72 (CI = 0.65-0.78) for Cyscope, and 0.71 (CI =
0.64-0.77) for QBC. Average cost per hour of use was the lowest ($2.04) with the
Cyscope. Turnaround time was the fastest with Cyscope (5 minutes). Conclusion.
Cyscope fluorescent microscope had the shortest turnaround time and is the most
cost-effective of all the malaria diagnostic instruments evaluated.
PMID- 27493828
TI - The Effects of POWER Training in Young and Older Adults after Stroke.
AB - Background. Approximately 35,000 strokes occur annually in adults below the age
of 40, and there is disappointingly little data describing their responses to
rehabilitation. The purpose of this analysis was to determine the effects of
Poststroke Optimization of Walking using Explosive Resistance (POWER) training in
young (<40 years) and older (>60 years) adults and to describe relationships
between training-induced improvements in muscular and locomotor function.
Methods. Data was analyzed from 16 individuals with chronic stroke who
participated in 24 sessions of POWER training. Outcomes included muscle power
generation, self-selected walking speed (SSWS), 6-minute walk test, Fugl-Meyer
motor assessment, Berg Balance Scale, and Dynamic Gait Index. Results. There were
no significant differences between groups at baseline. Within-group comparisons
revealed significant improvements in paretic and nonparetic knee extensor muscle
power generation in both groups. Additionally, young participants significantly
improved SSWS. Improvements in SSWS were more strongly associated with
improvements in power generation on both sides in young versus older
participants. Conclusions. Younger adults after stroke seem to preferentially
benefit from POWER training, particularly when increasing gait speed is a
rehabilitation goal. Future research should aim to further understand age-related
differences in response to training to provide optimal treatments for all
individuals following stroke.
PMID- 27493829
TI - Evaluation of Er,Cr:YSGG Laser Effect on Microshear Bond Strength of a Self
Adhesive Flowable Composite in the Dentin of Permanent Molar: An In Vitro Study.
AB - Aim and Background. Recently, new restorative materials such as self-adhesive
flowable composites, because of their simple use and no need to bonding and
etching, are considered important, particularly in pediatric dentistry. The aim
of this study is to evaluate the effect of Er,Cr:YSGG laser on microshear bond
strength of self-adhesive flowable composite on permanent teeth dentin in vitro.
Material and Methods. In this experimental study, 40 dentin sections were
prepared from healthy third molars and divided into two groups according to their
surface preparation by Er,Cr:YSGG laser or without laser, only with silicon
carbide paper. In each group, two groups of 10 teeth were treated with self
adhesive flowable composite (Dyad) and conventional flowable composite (acid etch
and bonding). Samples were stored in normal saline and after 48 hours their bond
strength was measured. The failure mode of samples was observed on
stereomicroscope. In order to analyse the results, the one way ANOVA and Tukey's
test for multiple comparisons were used. Result. The maximum bond strength was
related to conventional flowable composite with laser preparation group (24/21
Mpa). The lowest one was seen in Dyad composite without laser emitting (9/89
Mpa). The statistical difference between this two groups was significant (P value
= 0/0038). The microshear bond strength differences between Dyad composite groups
with laser preparation (mean = 16/427 +/- 1/79) and without laser preparation
(mean = 12/85 +/- 1/90) were statistically significant too (P value = 0/01).
Conclusion. Self-adhesive flowable composite has lower microshear bond strength
than conventional flowable composite. Moreover, the laser irradiation as a
surface treatment can improve this bond strength.
PMID- 27493831
TI - Ischemia-induced Angiogenesis is Attenuated in Aged Rats.
AB - To study whether focal angiogenesis is induced in aged rodents after permanent
distal middle cerebral artery occlusion (MCAO), young adult (3-month-old) and
aged (24-month-old) Fisher 344 rats underwent MCAO and sacrificed up to two
months after MCAO. Immunohistochemistry and synchrotron radiation
microangiography were performed to examine the number of newly formed blood
vessels in both young adult and aged rats post-ischemia. We found that the number
of capillaries and small arteries in aged brain was the same as young adult
brain. In addition, we found that after MCAO, the number of blood vessels in the
peri-infarct region of ipsilateral hemisphere in aged ischemic rats was
significantly increased compared to the aged sham rats (p<0.05). We also
confirmed that ischemia-induced focal angiogenesis occurred in young adult rat
brain while the blood vessel density in young adult ischemic brain was
significantly higher than that in the aged ischemic brain (p<0.05). Our data
suggests that focal angiogenesis in aged rat brain can be induced in response to
ischemic brain injury, and that aging impedes brain repairing and remodeling
after ischemic stroke, possible due to the limited response of angiogenesis.
PMID- 27493830
TI - Brain Atrophy, Anti-Smooth Muscle Antibody and Cognitive Impairment: An
Association Study.
AB - Cortical atrophy, neuronal loss, beta-amyloid deposition, neuritic plaques, and
neurofibrillary tangles are neuropathological key features in the Alzheimer's
disease (AD). Antibodies against beta-amyloid, neurotransmitters, microvascular
endothelium components and microglial cells have been detected in AD serum
suggesting that AD could be another autoimmune disease and provides a link
between vascular pathology, endothelium dysfunction and neuronal cells death. Aim
of the present study was to evaluate the association between autoantibody profile
and cognitive impairment in geriatric patients, accounting for ApoE genotype as a
potential confounding factor. Three hundred and forty-four geriatric patients,
attending the clinic for the cognitive decline, underwent a biochemical and
immunological profile, chest X-ray, cerebral computed tomography scan and
complete cognitive evaluation. All patients were also screened for the ApoE
genotype. A significantly higher prevalence of Anti-Smooth Muscle Antibody (ASMA)
positivity was found in 89/204 (43.63%) patients with diagnosed neuroradiological
signs of cerebral atrophy compared with 15/140 (10.71%) patients without the
condition (p<0.001). Multivariable logistic model evidenced that such association
was independent of patient's age, gender and Mini-Mental State Examination
(OR=8.25, 95%CI: 4.26-15.99) and achieved a good discriminatory power (c
statistic=0.783). Results were also independent of ApoE genotype, which resulted
not associated both with the presence of brain atrophy and with the presence of
ASMA positivity. Our results shows a strong association between brain atrophy and
ASMA positivity and are consistent with several studies that focused attention on
the mechanisms of endothelial immune response in the development of dementia.
PMID- 27493832
TI - Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response
and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage.
AB - Transient forebrain ischemia induces delayed death of the hippocampal pyramidal
neurons, particularly in the CA2 and medial CA1 area. Early pharmacological
inhibition of inflammatory response can ameliorate neuronal death, but it also
inhibits processes leading to tissue regeneration. Therefore, research efforts
are now directed to modulation of post-ischemic inflammation, with the aim to
promote beneficial effects of inflammation and limit adverse effects.
Transcription factor NF-kappaB plays a key role in the inflammation and cell
survival/apoptosis pathways. In the brain, NF-kappaB is predominantly found in
the form of a heterodimer of p65 (RelA) and p50 subunit, where p65 has a
transactivation domain while p50 is chiefly involved in DNA binding. In this
study, we subjected middle-aged Nfkb1 knockout mice (lacking p50 subunit) and
wild-type controls of both sexs to 17 min of transient forebrain ischemia and
assessed mouse performance in a panel of behavioral tests after two weeks of post
operative recovery. We found that ischemia failed to induce clear memory and
motor deficits, but affected spontaneous locomotion in genotype- and sex-specific
way. We also show that both the lack of the NF-kappaB p50 subunit and female sex
independently protected CA2 hippocampal neurons from ischemia-induced cell death.
Additionally, the NF-kappaB p50 subunit deficiency significantly reduced ischemia
induced microgliosis, astrogliosis, and neurogenesis. Lower levels of hippocampal
microgliosis significantly correlated with faster spatial learning. We conclude
that NF-kappaB regulates the outcome of transient forebrain ischemia in middle
aged subjects in a sex-specific way, having an impact not only on neuronal death
but also specific inflammatory responses and neurogenesis.
PMID- 27493833
TI - Mobility-Related Consequences of Reduced Lower-Extremity Peripheral Nerve
Function with Age: A Systematic Review.
AB - The objective of this study is to systematically review the relationship between
lower-extremity peripheral nerve function and mobility in older adults. The
National Library of Medicine (PubMed) was searched on March 23, 2015 with no
limits on publication dates. One reviewer selected original research studies of
older adults (>=65 years) that assessed the relationship between lower-extremity
peripheral nerve function and mobility-related outcomes. Participants, study
design and methods of assessing peripheral nerve impairment were evaluated and
results were reported and synthesized. Eight articles were identified, including
6 cross-sectional and 2 longitudinal studies. These articles investigated 6
elderly cohorts (4 from the U.S. and 2 from Italy): 3 community-dwelling
(including 1 with only disabled women and 1 without mobility limitations at
baseline), 1 with both community-dwelling and institutionalized residents, 1 from
a range of residential locations, and 1 of patients with peripheral arterial
disease. Mean ages ranged from 71-82 years. Nerve function was assessed by
vibration threshold (n=2); sensory measures and clinical signs and symptoms of
neuropathy (n=2); motor nerve conduction (n=1); and a combination of both sensory
measures and motor nerve conduction (n=3). Each study found that worse peripheral
nerve function was related to poor mobility, although relationships varied based
on the nerve function measure and mobility domain assessed. Six studies found
that the association between nerve function and mobility persisted despite
adjustment for diabetes. Evidence suggests that peripheral nerve function
impairment at various levels of severity is related to poor mobility independent
of diabetes. Relationships varied depending on peripheral nerve measure, which
may be particularly important when investigating specific biological mechanisms.
Future research needs to identify risk factors for peripheral nerve decline
beyond diabetes, especially those common in late-life and modifiable.
Interventions to preserve nerve function should be investigated with regard to
their effect on postponing or preventing disability in older adults.
PMID- 27493834
TI - Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative
Diseases.
AB - Degenerative diseases often strike older adults and are characterized by
progressive deterioration of cells, eventually leading to tissue and organ
degeneration for which limited effective treatment options are currently
available. Acid-sensing ion channels (ASICs), a family of extracellular H(+)
activated ligand-gated ion channels, play critical roles in physiological and
pathological conditions. Aberrant activation of ASICs is reported to regulate
cell apoptosis, differentiation and autophagy. Accumulating evidence has
highlighted a dramatic increase and activation of ASICs in degenerative
disorders, including multiple sclerosis, Parkinson's disease, Huntington's
disease, intervertebral disc degeneration and arthritis. In this review, we have
comprehensively discussed the critical roles of ASICs and their potential utility
as therapeutic targets in degenerative diseases.
PMID- 27493835
TI - Danggui-Shaoyao-San: New Hope for Alzheimer's Disease.
AB - Danggui-Shaoyao-San (DSS), also called Toki-shakuyaku-san (TJ-23) or
Dangguijakyak-san (DJS), is a well-known herbal formula (Angelica sinensis
(Oliv.) Diels., Ligusticum chuanxiong Hort., Paeonia lactiflora pall., Poria
cocos (Schw.) Wolf, Alisma orientalis (Sam.) Juzep., Atractylodes macrocephala
Koidz.), which has been widely used in oriental countries for the treatment of
various gynecological diseases. Recent studies show that DSS has an effect on
free radical-mediated neurological diseases and exhibits anti-inflammatory and
antioxidant activities and reduces cell apoptosis in the hippocampus. In
addition, DSS mediates the modulation of central monoamine neurotransmitter
systems and ameliorates dysfunction of the central cholinergic nervous system and
scopolamine-induced decrease in ACh levels. DSS improves the function of the
dopaminergic, adrenergic, and serotonergic nervous systems. Interestingly, DSS
can alleviate cognitive dysfunction of Alzheimer's disease (AD) patients,
suggesting that it is a useful therapeutic agent for AD. This paper reviews the
mechanism of DSS for the treatment of AD.
PMID- 27493837
TI - Population Aging in the European Information Societies: Towards a Comprehensive
Research Agenda in eHealth Innovations for Elderly.
AB - Population ageing is one of the major social and economic challenges of our
contemporary societies. With the advent of the information society, new research
and technological developments have been promoted in the field of assistive
technologies and information and communication technologies of benefit to elderly
people. This article examines the potentialities of new informatics developments
in generating solutions to better address elderly people's daily-life, especially
those with chronic illness and/or low autonomy. The authours attempt to propose a
research agenda, by exposing various strengts and weaknesses of eHealth
innovations for elderly, mainly grounded in secondary sources analysis.
PMID- 27493836
TI - The Role of Bone Marrow Microenvironment in Governing the Balance between
Osteoblastogenesis and Adipogenesis.
AB - In the adult bone marrow, osteoblasts and adipocytes share a common precursor
called mesenchymal stem cells (MSCs). The plasticity between the two lineages has
been confirmed over the past decades, and has important implications in the
etiology of bone diseases such as osteoporosis, which involves an imbalance
between osteoblasts and adipocytes. The commitment and differentiation of bone
marrow (BM) MSCs is tightly controlled by the local environment that maintains a
balance between osteoblast lineage and adipocyte. However, pathological
conditions linked to osteoporosis can change the BM microenvironment and shift
the MSC fate to favor adipocytes over osteoblasts, and consequently decrease bone
mass with marrow fat accumulation. This review discusses the changes that occur
in the BM microenvironment under pathological conditions, and how these changes
affect MSC fate. We suggest that manipulating local environments could have
therapeutic implications to avoid bone loss in diseases like osteoporosis.
PMID- 27493838
TI - Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective
Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model.
AB - Parkinson's disease (PD) is a progressive neurodegenerative disorder with
complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress
appears to play a critical role in the progression of PD. We demonstrated that
basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER
stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)
induced ER stress was involved in the progression of PD in rats. bFGF
administration improved motor function recovery, increased tyrosine hydroxylase
(TH)-positive neuron survival, and upregulated the levels of neurotransmitters in
PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF
treatment. Meanwhile, bFGF also increased expression of TH. The administration of
bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro.
Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially
reduced the protective effect of bFGF. This study provides new insight towards
bFGF translational drug development for PD involving the regulation of ER stress.
PMID- 27493840
TI - Evaluation of Pharmacokinetics, and Bioavailability of Higher Doses of
Tocotrienols in Healthy Fed Humans.
AB - BACKGROUND: Tocotrienols has been known to lower serum lipid parameters below 500
mg/d, while increase lipid parameters at higher dose of 750 mg/d. delta
Tocotrienol has a novel inflammatory property of concentration-dependent
inhibition and activation. Therefore, inhibition (anti-inflammatory) property of
tocotrienols at low doses is useful for cardiovascular disease, whereas,
activation (pro-inflammatory) property using high dose is found effective for
treatments of various types of cancer. We have recently described plasma
bioavailability of 125 mg/d, 250 mg/d and 500 mg/d doses of delta-tocotrienol in
healthy fed subjects, which showed dose-dependent increases in area under the
curve (AUC) and maximum concentration (Cmax). Hence, in the current study, higher
doses of tocotrienols have used to analyze its effect on plasma pharmacokinetic
parameters. AIMS: To evaluate the safety and bioavailability of higher doses (750
mg and 1000 mg) of annatto-based tocotrienols in healthy fed subjects. All four
isomers (alpha-, beta-, gamma-, delta-) of tocols (tocotrienols and tocopherols)
present in the plasmas of subjects were quantified and analyzed for various
pharmacokinetic parameters. STUDY DESIGN: An open-label, randomized study was
performed to analyze pharmacokinetics and bioavailability of delta-tocotrienol in
6 healthy fed subjects. All subjects (3/dose) were randomly assigned to one of
each dose of 750 mg or 1000 mg. Blood samples were collected at 0, 1, 2, 4, 6, 8
h intervals and all isomers of alpha-,beta-,gamma-,delta-tocotrienols, and
tocopherols in plasmas were quantified by HPLC. RESULTS: Oral administration of
750 and 1000 mg/d of tocotrienols resulted in dose-dependent increases in plasmas
(ng/ml) AUCt0-t8 6621, 7450; AUCt0-infinity 8688, 9633; AUMC t0-infinity 52497,
57199; MRT 6.04, 5.93; Cmax 1444, 1592 (P<0.05), respectively, of delta
tocotrienol isomer. Moreover, both doses also resulted in plasmas Tmax 3.33-4 h;
elimination half-life (t1/2 h) 2.74, 2.68; time of clearance (Cl-T, l/h) 0.086,
0.078; volume of distribution (Vd/f, mg/h) 0.34, 0.30; and elimination rate
constant (ke; h-1) 0.25, 0.17, respectively of delta- tocotrienol isomer. Similar
results of these parameters were reported for gamma-tocotrienol, beta-
tocotrienol, alpha-tocotrienol, delta-tocopherol, gamma-tocopherol, and beta
tocopherol, except for alpha- tocopherol. CONCLUSIONS: This study has described
pharmacokinetics using higher doses of 750 mg/d and 1000 mg/d of delta
tocotrienol. These results confirmed earlier findings that Tmax was 3-4 h for all
isomers of tocotrienols and tocopherols except for alpha-tocopherol (6 h). These
higher doses of tocotrienols were found safe in humans and may be useful for
treatments of various types of cancer, diabetes, and Alzheimer's disease.
PMID- 27493839
TI - Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of
Alzheimer's Disease.
AB - The extracellular matrix (ECM) is an environment that has various enzymes
attended in regeneration and restoration processes which is very important to
sustain physiological and biological functions of central nervous system (CNS).
One of the participating enzyme systems in ECM turnover is matrix
metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin
type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals.
Components of this family may be distinguished from the ADAM (A Disintegrin and
Metalloproteinase) family based on the multiple copies of thrombospondin 1-like
repeats. The considerable role of the ADAMTS in the CNS continues to develop.
Evidences indicate that ADAMTS play an important role in neuroplasticity as well
as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and
possible that ADAMTS family members may be utilized to develop therapies for CNS
pathologies, ischemic injuries, neurodegenerative and neurological diseases. To
understand and provide definitive data on ADAMTS to improve structural and
functional recovery in CNS injury and diseases, this review aimed to enlighten
the subject extensively to reach certain information on metalloproteinases and
related molecules/enzymes. It will be interesting to examine how ADAMTS
expression and action would affect the initiation/progression of above-mentioned
clinical situations, especially AD.
PMID- 27493841
TI - Persistence of Neutralizing Antibody Against Dengue Virus 2 After 70 Years from
Infection in Nagasaki.
AB - This study aimed to investigate the duration of humoral immune responses to
dengue virus (DENV) infection in Japanese who experienced acute febrile illness
with hemorrhagic manifestations 70 years ago, when an epidemic of dengue occurred
in Nagasaki, Japan, from 1942 to 1944. A Japanese volunteer requested serological
diagnosis of DENV infection in 2014 and donated blood sample to measure the
antibody titer against DENV by antiflavi IgG indirect ELISA, focus reduction
neutralization test, and plaque reduction neutralization test. The serum sample
of the volunteer was positive in flavi IgG ELISA and it indicated primary
infection. In the neutralization test, the highest neutralizing titer was >=218
for DENV-2. We report here the existence of DENV-specific antibodies in the serum
of a person after 70 years from infection. Published reports indicated that DENV
1 was responsible for the 1942-1944 outbreak in Nagasaki. However, our data
suggested that DENV-2 also played a role in this Nagasaki dengue epidemic.
PMID- 27493842
TI - Hemorrhagic Pilocytic Astrocytomas in Adults: A Case Report and Literature
Review.
AB - Pilocytic astrocytomas are histologically benign tumors, generally found in the
pediatric population. Onset of symptoms is generally insidious, predominantly
stemming from mass effect upon nearby structures. Patients harboring a pilocytic
astrocytoma may present with gait disturbance, headaches, cranial nerve deficits,
as well as hydrocephalus, depending on the exact location. Although cases of
adult pilocytic astrocytomas in the adult population are described, they are
quite uncommon. We present a case of an adult female presenting with acute
neurological compromise resulting from an acutely hemorrhagic posterior fossa
pilocytic astrocytoma. Her initial neurological assessment was consistent with a
Glasgow coma scale of 4T, as the patient was experiencing decerebrate posturing.
An emergent external ventricular drain was placed in the emergency department for
acute hydrocephalus as a temporizing measure, prior to evacuation of the
associated subdural and intratumoral hemorrhages, as well as resection of the
mass. After a long hospital course and extensive rehabilitation, the patient made
a remarkable recovery and eventually gave birth to a child via Caesarean section
three years after her initial presentation.
PMID- 27493843
TI - An Innovative and Portable Multimodal Pain Relief Device for the Management of
Neuropathic Low Back Pain - a Study from Kashmir (Southeast Asia).
AB - We developed a portable multimodal system with seven different mechanisms of pain
relief incorporated into a lumbar belt called the Comfort-N-Harmony Belt (C&H
belt). Here, we describe the technical details of the system and also summarize
the effects of this multimodal pain relieving technology as an adjuvant to
analgesics versus analgesics alone, on the level of pain, improvement of
psychological status, disability, and the quality of life in the patients with
neuropathic low back pain (LBP). We tracked the volunteers who were following up
at a tertiary health care center for the complaints of neuropathic LBP of minimum
three months duration and were on analgesics alone with no relief in the severity
of the pain. Study group A (n = 45) consisted of volunteers with LBP on C&H belt
therapy, along with the usually prescribed analgesic intake, and group B (n = 45)
with LBP volunteers on analgesics, plus a similar looking but plain leather belt
(placebo). For pain, the VAS (Visual Analogue Scale); for anxiety and depression,
the (HADS) Hospital Anxiety-Depression Scale; for disability, the RMDQ (Roland
Morris Disability Questionnaire); and for quality of life, (NHP) Nottingham
Health-Profile were used before and after the study period. There were no
significant differences in demographic variables between the groups (p < 0.05).
After the study period of one month, VAS, RMDQ, NHP-pain, NHP-physical activity,
and HADS scores in both groups were significantly improved compared to the pre
treatment scores (p < 0.05). Group A also showed significant improvements in the
scores of NHP-energy level and NHP-social isolation (p < 0.05). The post
treatment scores did not significantly show any difference between the two groups
(p > 0.05). However, in comparison of pre- and post-treatment scores, the pre
treatment score values of RMDQ, NHP-pain, NHP-physical activity, and NHP-social
isolation were much higher in group A compared to the group B, but still these
scores were, in a statistically significant manner, improved in group A compared
to the group B after the study period was over (p < 0.05). Multiple pain
relieving mechanisms in a portable device-based system, when used along with
analgesics, are effective in relieving pain, improving function and quality of
life, and help in relieving the associated anxiety and depression in patients
with chronic neuropathic LBP than the analgesics alone in the Kashmiri (Southeast
Asian) population.
PMID- 27493844
TI - A Prospective Cohort Evaluation of a Robotic, Auto-Navigating Operating
Microscope.
AB - The unique challenges inherent to microneurosurgery demand that we stay on the
forefront of new surgical technologies. Many believe the next major technological
advance in neurosurgery will be the widespread application of image-guided
robotics in the operating room. We evaluated a novel technology for image-guided
robotic auto-navigation of the operating microscope in a prospectively enrolled
cohort of patients. Twenty patients were prospectively enrolled for analysis.
Data were collected on the extent of resection, operative time, estimated blood
loss, time taken to set up the new software, and complications encountered.
Software accuracy, reliability, and usefulness in the case were subjectively
evaluated. The most commonly treated pathologies were cavernous malformation (n
= 5), arteriovenous malformation (n = 4), and meningioma (n = 4). The time to set
up the new software interface before the start of the operation was <60 seconds
in all cases. Subjective evaluation in each case revealed the robotic interface
to be accurate, reliable, and useful. The new technology was significantly more
useful in deeper lesions. The addition of image-guided robotic auto-positioning
features to the operating microscope has a great potential to advance the field
of neurosurgery. This study is the first prospective evaluation of such a
technology in a patient cohort. The results suggest that the newest robotic auto
positioning technology has the potential to improve the neurosurgeon's efficiency
and efficacy, thereby positively impacting patient safety and surgical outcomes,
especially in cases involving deep-seated lesions.
PMID- 27493845
TI - Scleroderma in a Patient on Capecitabine: Is this a Variant of Hand-Foot
Syndrome?
AB - Drug-induced scleroderma is a rare adverse effect of some chemotherapeutic drugs,
such as taxanes and bleomycin. Capecitabine, an oral fluoropyrimidine approved
for the treatment of metastatic breast and colon cancer, commonly causes
cutaneous side effects including the hand-and-foot syndrome (HFS). Scleroderma
like skin changes associated with HFS associated with capecitabine is rare.
However, diffuse scleroderma has never before been reported. We report a case of
capecitabine-induced diffuse/systemic scleroderma in an 86-year-old female
treated with capecitabine for metastatic colorectal cancer. She developed
progressive skin and visceral sclerosis involving the lungs. We discuss the
association between chemotherapy and scleroderma. We believe this is the first
case of diffuse/systemic capecitabine-induced scleroderma without the presence of
HFS. Early diagnosis is essential as fibrosis might be prevented in early stages.
The capecitabine should be discontinued as early as possible.
PMID- 27493846
TI - A Superior Cerebellar Convexity Two-Part Craniotomy to Access the Paramedian
Supra and Infratentorial Space: Technical Note.
AB - A craniotomy over the superior cerebellar convexity for approaches to this region
typically involves a small infratentorial craniotomy and then drilling down of
the bone to expose some portion of the transverse/sigmoid sinuses. The authors
describe the anatomy of the region and the method for a two-part paramedian
occipital and suboccipital craniotomy (supra and infratentorial) that may have
time-saving, safety, and cosmetic advantages. For this technique, a
supratentorial craniotomy is used to expose the transverse sinus from above, and
subsequently, dissection across the sinus over the cerebellar convexity can be
done under direct vision. The two bone pieces are joined on the inner table side
while plates for fixation above the superior nuchal line can be counter-sunk to
avoid post-operative pain from the prominence of screws. There is no need for
cranioplasty materials since there is no burring down of bone for adequate
exposure of the transverse sinus. The technique has been used by two senior
surgeons over the years convincing them of the speed, safety, and utility of the
technique. Here, the authors present a single example of the technique.
PMID- 27493847
TI - A Rare Presentation of Ganglion Cyst of the Elbow.
AB - INTRODUCTION: Ganglion cysts are benign soft tissue swellings commonly found in
the wrist. The presence of these cysts in the elbow is uncommon, and few case
reports have been reported for this condition at this location. These lesions can
compress on the neighbouring structures or cause restriction of the joint
movement. The awareness of this entity is a must, to arrive at an early
diagnosis. MATERIALS AND METHOD: We report a patient with swelling in the
anterolateral aspect of the elbow which had been causing intermittent pain for
the last 13 months. The MRI revealed a fluid-filled cystic swelling which was
communicating with the radio-capitellar joint. RESULTS: The lesion was excised in
toto, using anterolateral approach for the elbow, and sent for histopathological
examination which confirmed the diagnosis of a ganglion cyst. CONCLUSION: Thus,
due to the infrequent presentation, an awareness of this condition is necessary
to prevent a delay in diagnosis and its subsequent management.
PMID- 27493848
TI - A Rare Giant Cell Tumor of the Distal Fibula and its Management.
AB - Giant Cell Tumour (GCT) of the distal fibula is extremely rare and poses
challenges in the surgical management. Wide excision or intralesional curettage,
along with adjuvant chemical cauterisation can prevent the recurrence of GCT. The
excised bone gap needs reconstruction using tricortical iliac autograft and
supportive plate fixation. In addition to wide excision, preservation of ankle
mortise is advisable in locally aggressive and large lesions of the distal
fibula. We report a GCT of the distal fibula in a young female patient. As part
of the treatment, en bloc resection, chemical cauterisation with phenol, and
distal fibula reconstruction with a tricortical iliac crest bone graft was done.
Eighteen months after the treatment, the patient has no recurrence and her ankle
is stable with full range of movement. We suggest this method to be worthwhile
for the treatment of this uncommon lesion in quantifying recurrence and
functional outcome.
PMID- 27493849
TI - Physicochemical origin of high correlation between thermal stability of a protein
and its packing efficiency: a theoretical study for staphylococcal nuclease
mutants.
AB - There is an empirical rule that the thermal stability of a protein is related to
the packing efficiency or core volume of the folded state and the protein tends
to exhibit higher stability as the backbone and side chains are more closely
packed. Previously, the wild type and its nine mutants of staphylococcal nuclease
were compared by examining their folded structures. The results obtained were as
follows: The stability was not correlated with the number of intramolecular
hydrogen bonds, intramolecular electrostatic interaction energy, or degree of
burial of the hydrophobic surface; though the empirical rule mentioned above
held, it was not the proximate cause of higher stability; and the number of van
der Waals contacts N vdW, or equivalently, the intramolecular van der Waals
interaction energy was an important factor governing the stability. Here we
revisit the wild type and its nine mutants of staphylococcal nuclease using our
statistical-mechanical theory for hydration of a protein. A molecular model is
employed for water. We show that the pivotal factor is the magnitude of the water
entropy gain upon folding. The gain originates from an increase in the total
volume available to the translational displacement of water molecules coexisting
with the protein in the system. The magnitude is highly correlated with the
denaturation temperature T m. Moreover, the apparent correlation between N vdW
and T m as well as the empirical rule is interpretable (i.e., their
physicochemical meanings can be clarified) on the basis of the water-entropy
effect.
PMID- 27493850
TI - Three-dimensional vertex model for simulating multicellular morphogenesis.
AB - During morphogenesis, various cellular activities are spatiotemporally
coordinated on the protein regulatory background to construct the complicated,
three-dimensional (3D) structures of organs. Computational simulations using 3D
vertex models have been the focus of efforts to approach the mechanisms
underlying 3D multicellular constructions, such as dynamics of the 3D monolayer
or multilayer cell sheet like epithelia as well as the 3D compacted cell
aggregate, including dynamic changes in layer structures. 3D vertex models enable
the quantitative simulation of multicellular morphogenesis on the basis of single
cell mechanics, with complete control of various cellular activities such as cell
contraction, growth, rearrangement, division, and death. This review describes
the general use of the 3D vertex model, along with its applications to several
simplified problems of developmental phenomena.
PMID- 27493851
TI - The molecular dynamics of crawling migration in microtubule-disrupted
keratocytes.
AB - Cell-crawling migration plays an essential role in complex biological phenomena.
It is now generally believed that many processes essential to such migration are
regulated by microtubules in many cells, including fibroblasts and neurons.
However, keratocytes treated with nocodazole, which is an inhibitor of
microtubule polymerization - and even keratocyte fragments that contain no
microtubules - migrate at the same velocity and with the same directionality as
normal keratocytes. In this study, we discovered that not only these migration
properties, but also the molecular dynamics that regulate such properties, such
as the retrograde flow rate of actin filaments, distributions of vinculin and
myosin II, and traction forces, are also the same in nocodazole-treated
keratocytes as those in untreated keratocytes. These results suggest that
microtubules are not in fact required for crawling migration of keratocytes,
either in terms of migrating properties or of intracellular molecular dynamics.
PMID- 27493852
TI - Protein-protein interactions of mitochondrial-associated protein via
bioluminescence resonance energy transfer.
AB - Protein-protein interactions are essential biological reactions occurring at
inter- and intra-cellular levels. The analysis of their mechanism is generally
required in order link to understand their various cellular functions.
Bioluminescence resonance energy transfer (BRET), which is based on an enzymatic
activity of luciferase, is a useful tool for investigating protein-protein
interactions in live cells. The combination of the BRET system and biomolecular
fluorescence complementation (BiFC) would provide us a better understanding of
the hetero-oligomeric structural states of protein complexes. In this review, we
discuss the application of BRET to the protein-protein interactions of
mitochondrial-associated proteins and discuss its physiological relevance.
PMID- 27493853
TI - Specific interactions between alkali metal cations and the KcsA channel studied
using ATR-FTIR spectroscopy.
AB - The X-ray structure of KcsA, a eubacterial potassium channel, displays a
selectivity filter composed of four parallel peptide strands. The backbone
carbonyl oxygen atoms of these strands solvate multiple K(+) ions. KcsA
structures show different distributions of ions within the selectivity filter in
solutions containing different cations. To assess the interactions of cations
with the selectivity filter, we used attenuated total reflection Fourier
transform infrared (ATR-FTIR) spectroscopy. Ion-exchange-induced ATR-FTIR
difference spectra were obtained by subtracting the spectrum of KcsA soaked in
K(+) solution from that obtained in Li(+), Na(+), Rb(+), and Cs(+) solutions.
Large spectral changes in the amide-I and -II regions were observed upon
replacing K(+) with smaller-sized cations Li(+) and Na(+) but not with larger
sized cations Rb(+) and Cs(+). These results strongly suggest that the
selectivity filter carbonyls coordinating Rb(+) or Cs(+) adopt a conformation
similar to those coordinating K(+) (cage configuration), but those coordinating
Li(+) or Na(+) adopt a conformation (plane configuration) considerably different
from those coordinating K(+). We have identified a cation-type sensitive amide-I
band at 1681 cm(-1) and an insensitive amide-I band at 1659 cm(-1). The bands at
1650, 1639, and 1627 cm(-1) observed for Na(+)-coordinating carbonyls were almost
identical to those observed in Li(+) solution, suggesting that KcsA forms a
similar filter structure in Li(+) and Na(+) solutions. Thus, we conclude that the
filter structure adopts a collapsed conformation in Li(+) solution that is
similar to that in Na(+) solution but is in clear contrast to the X-ray crystal
structure of KcsA with Li(+).
PMID- 27493854
TI - Structural comparison between the open and closed forms of citrate synthase from
Thermus thermophilus HB8.
AB - The crystal structures of citrate synthase from the thermophilic eubacteria
Thermus thermophilus HB8 (TtCS) were determined for an open form at 1.5 A
resolution and for closed form at 2.3 A resolution, respectively. In the absence
of ligands TtCS in the open form was crystalized into a tetragonal form with a
single subunit in the asymmetric unit. TtCS was also co-crystallized with citrate
and coenzyme-A to form an orthorhombic crystal with two homodimers in the
asymmetric unit. Citrate and CoA are found in the active site situated between
the large domain and the small domain in all subunit whereas the complex shows
two distinct closed conformations, the fully closed form and partially closed
form. Structural comparisons are performed to describe conformational changes
associated with binding of products of TtCS. Upon binding of citrate, basic
residues in the active site move toward citrate and make a hydrogen bond network
in the active site, inducing a large-scale rotation of the small domain relative
to the large domain. CoA is sandwiched between the small and large domains and
then the cysteamine tail is inserted into the active site with a cooperative
rotation around mainchain dihedrals in the hinge region connecting helices M and
N. According to this rotation these helices are extended to close the active site
completely. The considerable flexibility and structural rearrangements in the
hinge region are crucial for an ordered bibi reaction in catalysis for microbial
CSs.
PMID- 27493856
TI - Time-resolved chemiluminescence of firefly luciferin generated by dissolving
oxygen in deoxygenated dimethyl sulfoxide containing potassium tert-butoxide.
AB - Chemiluminescence (CL) of firefly luciferin (Ln) consisting of red and green
emission peaks can be generated by dissolving oxygen (O2) gas in deoxygenated
dimethyl sulfoxide containing potassium tert-butoxide (t-BuOK) even without the
enzyme luciferase. In this study, the characteristics of CL of Ln are examined by
varying the concentrations of both Ln ([Ln]) and t-BuOK ([t-BuOK]). The time
courses of the green and the red luminescence signals are also measured using a
32-channel photo sensor module. Interestingly, addition of 18-crown-6 ether (18
crown-6), a good clathrate for K(+), to the reaction solution before exposure to
O2 changes the luminescence from green to red when [t-BuOK] = 20 mM and [18-crown
6] = 80 mM. Based on our experimental results, we propose a two-pathway model
where K(+) plays an important role in the regulation of Ln CL to explain the two
color luminescence observed from electronically excited oxyluciferin via
dioxetanone.
PMID- 27493855
TI - Investigation of glycan evolution based on a comprehensive analysis of
glycosyltransferases using phylogenetic profiling.
AB - Glycans play important roles in such cell-cell interactions as signaling and
adhesion, including processes involved in pathogenic infections, cancers, and
neurological diseases. Glycans are biosynthesized by multiple
glycosyltransferases (GTs), which function sequentially. Excluding mucin-type O
glycosylation, the non-reducing terminus of glycans is biosynthesized in the
Golgi apparatus after the reducing terminus is biosynthesized in the ER. In the
present study, we performed genome-wide analyses of human GTs by investigating
the degree of conservation of homologues in other organisms, as well as by
elucidating the phylogenetic relationship between cephalochordates and
urochordates, which has long been controversial in deuterostome phylogeny. We
analyzed 173 human GTs and functionally linked glycan synthesis enzymes by
phylogenetic profiling and clustering, compiled orthologous genes from the
genomes of other organisms, and converted them into a binary sequence based on
the presence (1) or absence (0) of orthologous genes in the genomes. Our results
suggest that the non-reducing terminus of glycans is biosynthesized by newly
evolved GTs. According to our analysis, the phylogenetic profiles of GTs resemble
the phylogenetic tree of life, where deuterostomes, metazoans, and eukaryotes are
resolved into separate branches. Lineage-specific GTs appear to play essential
roles in the divergence of these particular lineages. We suggest that
urochordates lose several genes that are conserved among metazoans, such as those
expressing sialyltransferases, and that the Golgi apparatus acquires the ability
to synthesize glycans after the ER acquires this function.
PMID- 27493857
TI - Subattomole detection of adiponectin in urine by ultrasensitive ELISA coupled
with thio-NAD cycling.
AB - Adiponectin is a hormone secreted from adipocytes, and it demonstrates
antidiabetic, anti-atherosclerotic, antiobesity and anti-inflammatory effects.
However, the patterns of change in urinary adiponectin levels in various diseases
remain unknown, because only trace amounts of the hormone are present in urine.
In the present study, we applied an ultrasensitive ELISA coupled with thio-NAD
cycling to measure urinary adiponectin levels. Spikeand-recovery tests using
urine confirmed the reliability of our ultrasensitive ELISA. The limit of
detection for adiponectin in urine was 2.3*10(-19) moles/assay (1.4 pg/mL). The
urinary adiponectin concentration ranged between 0.04 and 5.82 ng/mL in healthy
subjects. The pilot study showed that the urinary adiponectin levels, which were
corrected by the creatinine concentration, were 0.73+/-0.50 (ng/mg creatinine,
N=6) for healthy subjects, versus 12.02+/-3.85 (ng/mg creatinine, N=3) for
patients with diabetes mellitus (DM). That is, the urinary adiponectin levels
were higher (P<0.05) in DM patients than in healthy subjects. Further, these
urinary adiponectin levels tended to increase with the progression of DM
accompanied with nephropathy. Our method is thus expected to provide a simple,
rapid and reasonably priced test for noninvasive monitoring of the progression of
DM without the requirement of special tools.
PMID- 27493858
TI - Rotational motion of rhodamine 6G tethered to actin through oligo(ethylene
glycol) linkers studied by frequency-domain fluorescence anisotropy.
AB - Investigation of the rotational motion of a fluorescent probe tethered to a
protein helps to elucidate the local properties of the solvent and protein near
the conjugation site of the probe. In this study, we have developed an instrument
for frequency-domain fluorescence (FDF) anisotropy measurements, and studied how
the local properties around a protein, actin, can be elucidated from the
rotational motion of a dye tethered to actin. Rhodamine 6G (R6G) was attached to
Cys-374 using newly-synthesized R6G-maleimide with three different oligo(ethylene
glycol) (OEG) linker lengths. The time-resolved anisotropy decay of R6G tethered
to G-actin was revealed to be a combination of the two modes of the wobbling
motion of R6G and the tumbling motion of G-actin. The rotational diffusion
coefficient (RDC) of R6G wobbling was ~0.1 ns(-1) at 20 degrees C and increased
with OEG linker length. The use of the three R6G-actin conjugates of different
linker lengths was useful to not only figure out the linker length dependence of
the rotational motion of R6G but also validate the analyses. In the presence of a
cosolvent of glycerol, although the tumbling motion of G-actin was retarded in
response to the bulk viscosity, the wobbling motion of R6G tethered to actin
exhibited an increase of RDC as glycerol concentration increased. This finding
suggests an intricate relationship between the fluid properties of the bulk
solvent and the local environment around actin.
PMID- 27493859
TI - Case study on the evolution of hetero-oligomer interfaces based on the
differences in paralogous proteins.
AB - We addressed the evolutionary trace of hetero-oligomer interfaces by comparing
the structures of paralogous proteins; one of them is a monomer or homo-oligomer
and the other is a hetero-oligomer. We found different trends in amino acid
conservation pattern and hydrophobicity between homo-oligomer and hetero
oligomer. The degree of amino acid conservation in the interface of homo-oligomer
has no obvious difference from that in the surface, whereas the degree of
conservation is much higher in the interface of hetero-oligomer. The interface of
homo-oligomer has a few very conserved residue positions, whereas the residue
conservation in the interface of hetero-oligomer tends to be higher. In addition,
the interface of hetero-oligomer has a tendency of being more hydrophobic
compared with the one in homo-oligomer. We conjecture that these differences are
related to the inherent symmetry in homo-oligomers that cannot exist in hetero
oligomers. Paucity of the structural data precludes statistical tests of these
tendencies, yet the trend can be applied to the prediction of the interface of
hetero-oligomer. We obtained putative interfaces of the subunits in CPSF
(cleavage and polyadenylation specificity factor), one of the human pre-mRNA 3'
processing complexes. The locations of predicted interface residues were
consistent with the known experimental data.
PMID- 27493860
TI - Liquid-theory analogy of direct-coupling analysis of multiple-sequence alignment
and its implications for protein structure prediction.
AB - The direct-coupling analysis is a powerful method for protein contact prediction,
and enables us to extract "direct" correlations between distant sites that are
latent in "indirect" correlations observed in a protein multiple-sequence
alignment. I show that the direct correlation can be obtained by using a
formulation analogous to the Ornstein-Zernike integral equation in liquid theory.
This formulation intuitively illustrates how the indirect or apparent correlation
arises from an infinite series of direct correlations, and provides interesting
insights into protein structure prediction.
PMID- 27493861
TI - Microbial rhodopsins: wide distribution, rich diversity and great potential.
AB - One of the major topics in biophysics and physicobiology is to understand and
utilize biological functions using various advanced techniques. Taking advantage
of the photoreactivity of the seven-transmembrane rhodopsin protein family has
been actively investigated by a variety of methods. Rhodopsins serve as models
for membrane-embedded proteins, for photoactive proteins and as a fundamental
tool for optogenetics, a new technology to control biological activity with
light. In this review, we summarize progress of microbial rhodopsin research from
the viewpoint of distribution, diversity and potential.
PMID- 27493862
TI - Analysis of water channels by molecular dynamics simulation of heterotetrameric
sarcosine oxidase.
AB - A precise 100-ns molecular dynamics simulation in aquo was performed for the
heterotetrameric sarcosine oxidase bound with a substrate analogue,
dimethylglycine. The spatial region including the protein was divided into small
rectangular cells. The average number of the water molecules locating within each
cell was calculated based on the simulation trajectory. The clusters of the cells
filled with water molecules were used to determine the water channels. The
narrowness of the channels, the average hydropathy indices of the residues of the
channels, and the number of migration events of water molecules through the
channels were consistent with the selective transport hypothesis whereby tunnel
T3 is the pathway for the exit of the iminium intermediate of the enzyme
reaction.
PMID- 27493863
TI - Structural role of two histidines in the (6-4) photolyase reaction.
AB - Photolyases (PHRs) are DNA repair enzymes that revert UV-induced photoproducts,
either cyclobutane pyrimidine dimers (CPD) or (6-4) photoproducts (PPs), into
normal bases to maintain genetic integrity. (6-4) PHR must catalyze not only
covalent bond cleavage, but also hydroxyl or amino group transfer, yielding a
more complex mechanism than that postulated for CPD PHR. Previous mutation
analysis revealed the importance of two histidines in the active center, H354 and
H358 for Xenopus (6-4) PHR, whose mutations significantly lowered the enzymatic
activity. Based upon highly sensitive FTIR analysis of the repair function, here
we report that both H354A and H358A mutants of Xenopus (6-4) PHR still maintain
their repair activity, although the efficiency is much lower than that of the
wild type. Similar difference FTIR spectra between the wild type and mutant
proteins suggest a common mechanism of repair in which (6-4) PP binds to the
active center of each mutant, and is released after repair, as occurs in the wild
type. Similar FTIR spectra also suggest that a decrease in volume by the H-to-A
mutation is possibly compensated by the addition of water molecule( s). Such a
modified environment is sufficient for the repair function that is probably
controlled by proton-coupled electron transfer between the enzyme and substrate.
On the other hand, two histidines must work in a concerted manner in the active
center of the wild-type enzyme, which significantly raises the repair efficiency.
PMID- 27493864
TI - Structures of the troponin core domain containing the cardiomyopathy-causing
mutants studied by small-angle X-ray scattering.
AB - Troponin (Tn), consisting of three subunits, TnC, TnI, and TnT, is a protein in
the thin filaments in muscle, and, together with another thin-filament protein
tropomyosin (Tm), plays a major role in regulation of muscle contraction. Various
mutations of Tn cause familial hypertrophic cardiomyopathy. These mutations are
directly related to aberrations in this regulatory mechanism. Here we focus on
the mutations E244D and K247R of TnT, which reside in the middle of the pathway
of the Ca(2+)-binding signal from TnC to Tm. These mutations induce an increase
in the maximum tension of cardiac muscle without changes in Ca(2+)-sensitivity.
As a first step toward elucidating the molecular mechanism underlying this
functional aberration, we carried out small-angle X-ray scattering experiments on
the Tn core domain containing the wild type subunits and those containing the
mutant TnT in the absence and presence of Ca(2+). Changes in the overall shape
induced by the mutations were detected for the first time by the changes in the
radius of gyration and the maximum dimension between the wild type and the
mutants. Analysis of the scattering curves by model calculations shows that TnC
adopts a dumbbell structure regardless of the mutations, and that the mutations
change the distributions of the conformational ensembles so that the flexible N-
and C-terminal regions of TnT become close to the center of the whole moelcule.
This suggests, since these regions are related to the Tn-Tm interactions, that
alteration of the Tn-Tm interactions induced by the mutations causes the
functional aberration.
PMID- 27493865
TI - Diet composition as a source of variation in experimental animal models of cancer
cachexia.
AB - BACKGROUND: A variety of experimental animal models are used extensively to study
mechanisms underlying cancer cachexia, and to identify potential treatments. The
important potential confounding effect of dietary composition and intake used in
many preclinical studies of cancer cachexia is frequently overlooked. Dietary
designs applied in experimental studies should maximize the applicability to
human cancer cachexia, meeting the essential requirements of the species used in
the study, matched between treatment and control groups as well as also being
generally similar to human consumption. METHODS: A literature review of
scientific studies using animal models of cancer and cancer cachexia with dietary
interventions was performed. Studies that investigated interventions using lipid
sources were selected as the focus of discussion. RESULTS: The search revealed a
number of nutrient intervention studies (n = 44), with the majority including n-3
fatty acids (n = 16), mainly eicosapentaenoic acid and/or docosahexaenoic acid. A
review of the literature revealed that the majority of studies do not provide
information about dietary design; food intake or pair-feeding is rarely reported.
Further, there is a lack of standardization in dietary design, content, source,
and overall composition in animal models of cancer cachexia. A model is proposed
with the intent of guiding dietary design in preclinical studies to enable
comparisons of dietary treatments within the same study, translation across
different study designs, as well as application to human nutrient intakes.
CONCLUSION: The potential for experimental endpoints to be affected by variations
in food intake, macronutrient content, and diet composition is likely. Diet
content and composition should be reported, and food intake assessed. Minimum
standards for diet definition in cachexia studies would improve reproducibility
of pre-clinical studies and aid the interpretation and translation of results to
humans with cancer.
PMID- 27493866
TI - Sarcopenic obesity and myosteatosis are associated with higher mortality in
patients with cirrhosis.
AB - BACKGROUND AND AIMS: Obesity is frequently associated with cirrhosis, and
cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of
adipose tissue, culminating in the condition of sarcopenic obesity. Additionally,
muscle depletion is characterized by both a reduction in muscle size and
increased proportion of muscular fat, termed myosteatosis. In this study, we
aimed to establish the frequency and clinical significance of sarcopenia,
sarcopenic obesity and myosteatosis in cirrhotic patients. METHODS: We analysed
678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were
analysed by CT scan using the third lumbar vertebrae skeletal muscle and
attenuation indexes, using previously validated gender-and body mass index
specific cutoffs. RESULTS: Patients were predominately men (n = 457, 67%), and
cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153
(23%), non-alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver
disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%).
Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had
myosteatosis (52%). Patients with sarcopenia (22 +/- 3 vs. 95 +/- 22 months, P <
0.001), sarcopenic obesity (22 +/- 3 vs. 95 +/- 22 months, P < 0.001), and
myosteatosis (28 +/- 5 vs. 95 +/- 22 months, P < 0.001) had worse median survival
than patients without muscular abnormalities. By multivariate Cox regression
analysis, both sarcopenia [hazard ratio (HR) 2.00, 95% confidence interval (CI)
1.44-2.77, P < 0.001], and myosteatosis (HR 1.42, 95% CI 1.02-1.07, P = 0.04)
were associated with mortality. CONCLUSIONS: Sarcopenia, sarcopenic obesity and
myosteatosis are often present in patients with cirrhosis, and sarcopenia and
myosteatosis are independently associated with a higher long-term mortality in
cirrhosis.
PMID- 27493867
TI - Prevalence of sarcopenia among community-dwelling elderly of a medium-sized South
American city: results of the COMO VAI? study.
AB - BACKGROUND: There is insufficient data concerning sarcopenia prevalence in South
America. The aim of this study was to estimate sarcopenia prevalence and its
clinical subgroups in a Southern Brazilian city. METHODS: A cross-sectional
population-based study was performed among community-dwelling elderly aged 60
years or over. Subjects were evaluated according to the European Working Group on
Sarcopenia in Older People established criteria. Muscle mass was estimated by
calf circumference (CC). Cut-off CC points were defined by a subsample's dual X
ray absorptiometry estimation of the appendicular skeletal muscle mass index
(ASMI), which was subsequently compared with the values of a young adult
population from the same city. Muscle strength was measured by manual
dynamometry. Muscle performance was assessed through the 4 m gait speed test.
RESULTS: The three diagnostic tests were performed in 1291 subjects. CC of <=34
cm (males) and <=33 cm (females) were defined as indicatives of low ASMI. The
overall sarcopenia prevalence was 13.9% (CI95% 12.0; 15.8%). Its frequency was
significantly higher among elderly with low schooling, without a partner, with
low socioeconomic status, smokers, inactive, and with low body mass index. A
higher prevalence of pre-sarcopenia was found in the youngest elderly; a higher
prevalence of the clinical stages of the syndrome was found in older age groups.
CONCLUSIONS: Approximately one in ten elderly aged 60-69 years was in the
preclinical stage of the disease. This is the age group in which public policies
should focus to establish early diagnosis and prevent clinical progression of the
syndrome.
PMID- 27493868
TI - Association of estimated glomerular filtration rate with all-cause and
cardiovascular mortality: the role of malnutrition-inflammation-cachexia
syndrome.
AB - BACKGROUND: Previous studies have demonstrated that high estimated glomerular
filtration rate (eGFR) is paradoxically associated with an increased risk of
mortality, and the association becomes more predominant in older people. However,
the role of malnutrition-inflammation-cachexia syndrome (MICS) in the association
between eGFR and mortality has never been explored. METHODS: We conducted a
community-based cohort study using data from the Taipei City Elderly Health
Examination Database, collected during the period 2001-10. All participants aged
>=65 years were included and stratified by the absence or presence of MICS, which
is defined as the presence of at least one of the following markers: body mass
index <22 kg/m(2), serum albumin <3.0 mg/dL, or Geriatric Nutritional Risk Index
(GNRI) <98. The study endpoints were all-cause and cardiovascular mortality.
RESULTS: A total of 131 354 participants were identified and categorized
according to the chronic kidney disease stage based on eGFR. Compared with the
reference eGFR of 60-89 mL/min/1.73 m(2), the overall and cardiovascular
mortality risks were markedly high in the groups with eGFR of <30 mL/min/1.73
m(2) [overall: adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI),
1.72-2.00; cardiovascular: aHR, 1.87; 95% CI, 1.60-2.19] and >=90 mL/min/1.73
m(2) (overall: aHR, 1.23; 95% CI, 1.13-1.34; cardiovascular: aHR, 1.28; 95% CI,
1.06-1.54). In the absence of MICS, high eGFR was associated with lower mortality
risk (aHR, 0.71; 95% CI, 0.62-0.80), and the U-shaped relationship disappeared.
Subgroup analyses produced consistent results. CONCLUSIONS: MICS could influence
the association observed between high eGFR and mortality in older people,
particularly in those with low body mass index, albumin level, GNRI, and very low
serum creatinine level.
PMID- 27493869
TI - Muscle wasting and adipose tissue browning in infantile nephropathic cystinosis.
AB - BACKGROUND: Muscle wasting is a common complication in patients with infantile
nephropathic cystinosis, but its mechanism and association with energy metabolism
is not known. We define the metabolic phenotype in Ctns(-/-) mice, an established
murine model of infantile nephropathic cystinosis, with focus on muscle wasting
and energy homeostasis. METHODS: Male Ctns(-/-) mice and wild-type (WT) controls
were studied at 1, 4, 9, and 12 months of age. As Ctns(-/-) mice started to
develop chronic kidney disease (CKD) at 9 months of age, 9- and 12-month-old
Ctns(-/-) mice were also compared with age-matched WT mice with CKD. Serum and
urine chemistry and energy homeostasis parameters were measured. Skeletal muscle
histomorphometry and in vivo muscle function were measured. We studied expression
of genes involved in muscle mass regulation, thermogenesis, energy metabolism,
adipogenesis, and adipose tissue browning in Ctns(-/-) mice. RESULTS: Ctns(-/-)
mice showed loss of weight and lean mass and increased energy expenditure. Ctns(
/-) mice exhibited abnormal energy homeostasis before the onset of their CKD.
Food intake in Ctns(-/-) mice was comparable with age-matched WT controls.
However, significantly lower total body mass starting at 1 month of age and
increased energy expenditure at 4 months of age preceded the onset of CKD at 9
months of age in Ctns(-/-) mice. Muscle accept content in 1- and 4-month-old
Ctns(-/-) mice was significantly lower than that in age-matched WT controls. At
12 months of age, muscle fibre area and in vivo muscle strength was reduced in
Ctns(-/-) mice than that in WT or CKD controls. Muscle wasting in Ctns(-/-) mice
was associated with inhibition of myogenesis, activation of muscle proteolysis
pathways, and overexpression of pro-inflammatory cytokines. Increased energy
expenditure was associated with elevation of thermogenesis in skeletal muscle and
adipose tissues. The development of beige adipocytes in Ctns(-/-) mice is a novel
finding. Expression of beige adipose cell surface markers (CD137, Tmem26, and
Tbx1) and uncoupling protein-1, which is a brown adipose tissue marker, was
observed in inguinal white adipose tissue of Ctns(-/-) mice. Expression of key
molecules implicated in the pathogenesis of adipose tissue browning (Cox2,
cytochrome c oxidase subunit II; PGF2alpha, prostaglandin F2alpha; IL-1alpha,
interleukin 1alpha; IL-6, interleukin 6; TNF-alpha, tumor necrosis factor alpha)
was significantly increased in inguinal white adipose tissue of Ctns(-/-) mice
than that in WT controls. CONCLUSION: This study describes a mouse model of
nephropathic cystinosis presenting with profound muscle wasting. The mechanism
for hypermetabolism in Ctns(-/-) mice may involve up-regulation of thermogenesis
pathways in skeletal muscle and adipose tissues. This study demonstrates, for the
first time, the development of beige adipocytes in Ctns(-/-) mice. Understanding
the underlying mechanisms of adipose tissue browning in cystinosis may lead to
novel therapy.
PMID- 27493870
TI - Muscle RING-finger 2 and 3 maintain striated-muscle structure and function.
AB - BACKGROUND: The Muscle-specific RING-finger (MuRF) protein family of E3 ubiquitin
ligases is important for maintenance of muscular structure and function. MuRF
proteins mediate adaptation of striated muscles to stress. MuRF2 and MuRF3 bind
to microtubules and are implicated in sarcomere formation with noticeable
functional redundancy. However, if this redundancy is important for muscle
function in vivo is unknown. Our objective was to investigate cooperative
function of MuRF2 and MuRF3 in the skeletal muscle and the heart in vivo.
METHODS: MuRF2 and MuRF3 double knockout mice (DKO) were generated and
phenotypically characterized. Skeletal muscle and the heart were investigated by
morphological measurements, histological analyses, electron microscopy,
immunoblotting, and real-time PCR. Isolated muscles were subjected to in vitro
force measurements. Cardiac function was determined by echocardiography and
working heart preparations. Function of cardiomyocytes was measured in vitro.
Cell culture experiments and mass-spectrometry were used for mechanistic
analyses. RESULTS: DKO mice showed a protein aggregate myopathy in skeletal
muscle. Maximal force development was reduced in DKO soleus and extensor
digitorum longus. Additionally, a fibre type shift towards slow/type I fibres
occurred in DKO soleus and extensor digitorum longus. MuRF2 and MuRF3-deficient
hearts showed decreased systolic and diastolic function. Further analyses
revealed an increased expression of the myosin heavy chain isoform beta/slow and
disturbed calcium handling as potential causes for the phenotype in DKO hearts.
CONCLUSIONS: The redundant function of MuRF2 and MuRF3 is important for
maintenance of skeletal muscle and cardiac structure and function in vivo.
PMID- 27493871
TI - Degenerin channel activation causes caspase-mediated protein degradation and
mitochondrial dysfunction in adult C. elegans muscle.
AB - BACKGROUND: Declines in skeletal muscle structure and function are found in
various clinical populations, but the intramuscular proteolytic pathways that
govern declines in these individuals remain relatively poorly understood. The
nematode Caenorhabditis elegans has been developed into a model for identifying
and understanding these pathways. Recently, it was reported that UNC
105/degenerin channel activation produced muscle protein degradation via an
unknown mechanism. METHODS: Generation of transgenic and double mutant C.
elegans, RNAi, and drug treatments were utilized to assess molecular events
governing protein degradation. Western blots were used to measure protein
content. Cationic dyes and adenosine triphosphate (ATP) production assays were
utilized to measure mitochondrial function. RESULTS: unc-105 gain-of-function
mutants display aberrant muscle protein degradation and a movement defect; both
are reduced in intragenic revertants and in let-2 mutants that gate the
hyperactive UNC-105 channel. Degradation is not suppressed by interventions
suppressing proteasome-mediated, autophagy-mediated, or calpain-mediated
degradation nor by suppressors of degenerin-induced neurodegeneration. Protein
degradation, but not the movement defect, is decreased by treatment with caspase
inhibitors or RNAi against ced-3 or ced-4. Adult unc-105 muscles display a time
dependent fragmentation of the mitochondrial reticulum that is associated with
impaired mitochondrial membrane potential and that correlates with decreased
rates of maximal ATP production. Reduced levels of CED-4, which is sufficient to
activate CED-3 in vitro, are observed in unc-105 mitochondrial isolations.
CONCLUSIONS: Constitutive cationic influx into muscle appears to cause caspase
degradation of cytosolic proteins as the result of mitochondrial dysfunction,
which may be relevant to ageing and sarcopenia.
PMID- 27493872
TI - White adipose tissue cells and the progression of cachexia: inflammatory
pathways.
AB - BACKGROUND: Cachexia is a systemic syndrome leading to body wasting, systemic
inflammation, and to metabolic chaos. It is a progressive condition, and little
is known about its dynamics. Detection of the early signs of the disease may lead
to the attenuation of the associated symptoms. The white adipose tissue is an
organ with endocrine functions, capable of synthesising and secreting a plethora
of proteins, including cytokines, chemokines, and adipokines. It is well
established that different adipose tissue depots demonstrate heterogeneous
responses to physiological and pathological stimuli. The present study aimed at
providing insight into adipocyte involvement in inflammation along the
progression of cachexia. METHODS: Eight-weeks-old male rats were subcutaneously
inoculated with a Walker 256 carcinosarcoma cell suspension (2 * 10(7) cells in
1.0 mL; tumour-bearing, T) or Phosphate-buffered saline (control, C). The
retroperitoneal, epididymal, and mesenteric adipose pads were excised on Days 0,
7, and 14 post-tumour cell injection, and the adipocytes were isolated. RESULTS:
Mesenteric and epididymal adipocytes showed up-regulation of IL-1beta protein
expression and activation of the inflammasome pathway, contributing for whole
tissue inflammation. The stromal vascular fraction of the retroperitoneal adipose
tissue, on the other hand, seems to be the major contributor for the inflammation
in this specific pad. CONCLUSION: Adipocytes seem to play a relevant role in the
establishment of white adipose tissue inflammation, through the activation of the
NF-kappaB and inflammasome pathways. In epididymal adipocytes, induction of the
inflammasome may be detected already on Day 7 post-tumour cell inoculation.
PMID- 27493873
TI - p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice.
AB - AIM: We investigated the pathway of autophagy signaling linked to sarcopenia of
mice. METHODS: Young adult (3-month) and aged (24- month) C57BL/6J mice were
used. Using real-time PCR, Western blotting, and immunohistochemical microscopy,
we evaluated the amounts of p62/SQSTM1, LC3, and Beclin-1 in the quadriceps
muscle change with aging in mice. RESULTS: Marked fiber atrophy (30%) and many
fibers with central nuclei were observed in the aged mice. Western blotting using
homogenate of the cytosolic fraction clearly showed that the amounts of
p62/SQSTM1 and Beclin-1 proteins were significantly increased in the aged
skeletal muscle. The amounts of these proteins in both nuclear and membrane
fractions did not change significantly with age. Immunofluorescence labeling
indicated that aged mice more frequently possessed p62/SQSTM1-positive fibers in
the cytosol in quadriceps muscle than young ones (aged: 14% vs. young: 1%). In
aged muscle, p62/SQSTM1-positive fibers were significantly smaller than the
surrounding p62/SQSTM1-negative fibers. Aging did not elicit significant changes
in the mRNA levels of p62/SQSTM1 and Beclin-1, but decreased LC3 mRNA level. In
aged muscle, the location of p62/SQSTM1 immunoreactivity was similar to that of
Beclin-1 protein, but not LC3. CONCLUSION: Sarcopenia in mice appears to include
a marked defect of autophagy signaling.
PMID- 27493876
TI - The concept that focuses on oral motor and feeding function in cancer patients
with muscle wasting: Skeletal muscle mass is associated with severe dysphagia in
cancer patients.
PMID- 27493875
TI - Salidroside alleviates cachexia symptoms in mouse models of cancer cachexia via
activating mTOR signalling.
AB - BACKGROUND: Cachexia has a devastating impact on survival and quality of life for
many cancer patients and contributes to nearly one-third of all cancer deaths;
also, it is associated with poor responses to chemotherapy and survival. A better
understanding of the underlying mechanisms of cancer-associated cachexia (CAC),
coupled with effective therapeutic approaches, will improve management of
progressive functional impairment in cancer patients. Salidroside, a
phenylpropanoid glycoside in Rhodiola rosea L, has been reported to possess
potential anti-fatigue, anti-ageing, and anti-Alzheimer's disease properties. It
is widely consumed as a nutritional supplement, but its effects on CAC and the
possible mechanism remain a mystery. METHODS: In the murine models of cachexia
induced by CT-26 and Lewis lung carcinoma (LLC) tumour, respectively, main
features of CAC were determined after treatment of salidroside or chemotherapy.
In vitro experiments were performed using murine C2C12 myotubes, which were
treated by tumour necrosis factor-alpha. Levels of several critical muscle
related signal proteins such as mammalian target of rapamycin (mTOR), p-mTOR, and
myosin heavy chain (MyHC) were examined using western blot both in vitro and in
vivo. RESULTS: In the present study, we showed the exciting effect of salidroside
on the treatment of CAC. In CT-26 and LLC models, respectively, salidroside
treatment could effectively preserve the tumour-free body weight, decrease loss
of adipose and gastrocnemius muscles, alleviate tumour burden, and prolong their
survival time. Additionally, in combined chemotherapy, salidroside could
synergistically enhance the anti-tumour activity of cisplatin, especially
decreased or eliminated chemotherapy-induced cachexia. Further analysis
demonstrated that salidroside could significantly increase expression of mTOR, p
mTOR, and MyHC in gastrocnemius muscle. Also, results in vitro showed that
salidroside could not only obviously increase mTOR, p-mTOR, and MyHC expression
in C2C12 myotubes but also effectively rescue their down-regulation induced by
tumour necrosis factor-alpha. CONCLUSIONS: In the current study, the exciting
effect of salidroside on CAC suggested that salidroside supplementation might be
a promising approach for a multi-targeted therapy for the treatment of CAC.
PMID- 27493874
TI - Diabetic mice exhibited a peculiar alteration in body composition with
exaggerated ectopic fat deposition after muscle injury due to anomalous cell
differentiation.
AB - BACKGROUND: Sarcopenic obesity, age-related muscle loss, which is compensated by
an increase in fat mass, impairs quality of life in elderly people. Although the
increase in intramuscular fat is associated with decreased insulin sensitivity
and increased metabolic risk factors, the origin of diabetes-associated
intramuscular fat has not been elucidated. Here, we investigated intramuscular
fat deposition using a muscle injury model in type 2 diabetic mice. METHODS: Male
8-week-old C57BL/6 and 8-week-old and 26-week-old KKAy underwent intramuscular
injection of cardiotoxin (Ctx) (100 MUL/10 MUM) into the tibialis anterior (TA)
muscles. After 2 weeks, the muscles were removed and evaluated. RESULTS: KKAy
exhibited impaired muscle regeneration and ectopic fat deposition. Such
impairment was more marked in older KKAy. These changes were also observed in
another diabetic mouse model, db/db and diet-induced obese mice but not in
streptozocin-induced diabetic mice. Deposited fat was platelet-derived growth
factor (PDGF) receptor alpha positive and its cytoskeleton was stained with
Masson's trichrome, indicating it to be of fibro-adipocyte progenitor cell
origin. Expression of a myogenic marker, myoD, was lower and that of PDGF
receptor alpha and CCAAT/enhancer binding protein (CEBP) alpha was higher in Ctx
injured TA of KKAy compared with that of C57BL/6. Peroxisome proliferator
activated receptor gamma (PPARgamma) was highly expressed in fat-forming lesions
in older KKAy. Treatment with all-trans retinoic acid prevented the formation of
intramuscular fat; however, treatment with GW9662, a PPARgamma antagonist,
increased the fibrotic change in muscle. CONCLUSIONS: Diabetic mice showed
impaired muscle regeneration with fat deposition, suggesting that diabetes may
enhance sarcopenic obesity through a mechanism involving anomalous fibro
adipocyte progenitor cell differentiation.
PMID- 27493877
TI - Growth differentiation factor-15 as a prognostic biomarker in cancer patients.
PMID- 27493878
TI - Opioid Use in the Twenty First Century: Similarities and Differences Across
National Borders.
AB - The global prevalence in the use of opiates and opioids has remained stable,
though there were some unprecedented recent increases in opioid use and
associated mortality and morbidity in the United States. Internationally, there
is a strong tendency for consolidation of drug treatment strategies in favor of
more systematic, structured and balanced approaches to regional and national drug
policies. However, there are considerable differences in the scope, focus, and
implementation of national drug policies and the political context is shaping
drug prevention, treatment and rehabilitation efforts to an extent not typically
observed in other public health domains. As a result, though in theory, there is
a considerable multi-national agreement about the efficacy and effectiveness of
different treatment modalities for opioid dependence, in practice, there are
striking differences among different world regions and countries in the degree of
implementation of these treatment modalities into clinical practice. Such
discrepancies between theory and practice are observed even in high-income
countries such as the United States and European Union member states, where
evidence-based treatment modalities are still not well implemented into clinical
practice. Despite the lack of evidence-based support for the role of
detoxification as a stand-alone treatment for opioid use disorders, it appears to
be the most widely used intervention for opioid use across the world.
PMID- 27493879
TI - Response to: Letter to the Editor Regarding: The Expanding Phenotype of MELAS
Caused by the m.3291 T > C tRNA Mutation E Kelland, C. A. Rupar, Asuri N. Prasad,
K. Y. Tay, A. Downie and C. Prasad (1) by Josef Finsterer, MD, PhD [1], Sinda
Zarrouk-Mahjoub, PhD [2] [1] Krankenanstalt Rudolfstiftung, Vienna [2] Genomics
Platform, Pasteur Institute of Tunis, Tunisia.
PMID- 27493880
TI - Barriers to drug adherence in the treatment of urea cycle disorders: Assessment
of patient, caregiver and provider perspectives.
AB - Patients and families living with metabolic disorders face challenging dietary
and drug treatment regimens. On the hypothesis that poor palatability, volume and
frequency of drug/formula administration contribute to treatment non-adherence
and hyperammonemic episodes, a survey was conducted of patient, caregiver (CG)
and physician perspectives on treatments used in urea cycle disorders (UCD).
METHODS: A paper and online survey assessed experience with UCD medications,
medical foods and dietary supplements. RESULTS: 25 physicians, 52 adult patients
and 114 CG responded. In 2009, the most common UCD-specific intervention reported
by patients included sodium phenylbutyrate (60%), followed by l-citrulline (46%),
amino acid medical foods (15%), l-arginine preparations (18%), and sodium
benzoate (8%). Only 36% of patients reported experiencing no hyperammonemic
episodes in the last 2 years. The most commonly reported cause of hyperammonemic
episodes was infection or other acute illnesses, followed by dietary
indiscretion, side effects of medications, and drug non-adherence. Most patients,
caregivers and physicians (> 75%) ranked nitrogen-scavenging medications, l
citrulline, l-arginine, and medical foods as "effective" or "very effective." Non
adherence was common (e.g. 18% of patients admitted to missing sodium
phenylbutyrate "at least once a week" and "at least one a day"). Barriers to
adherence included taste of medications, frequency of drug administration, number
of pills, difficulty swallowing pills, side effects, forgetting to take
medications, and high cost. Strategies to mitigate the gastrointestinal side
effects of medications included the use of gastric tubes and acid reflux
medications. Physicians indicated that 25% and 33% of pediatric and adult
patients, respectively, were given less than the recommended dose of sodium
phenylbutyrate due to concerns of tolerance, administration, and cost.
CONCLUSIONS: Despite positive views of their effectiveness, respondents found
medications, medical foods and dietary supplements difficult to take and viewed
adherence as inadequate, thus contributing to hyperammonemic episodes.
PMID- 27493881
TI - On the Origin of Cells and Derivation of Thyroid Cancer: C Cell Story Revisited.
AB - We will highlight and put into perspective new lineage tracing data from genetic
studies in mice indicating that the genuine progenitors to C cells arise in the
endoderm germ layer. This overturns the current concept of a neural crest origin
of thyroid C cells referred to in every textbook and dedicated paper to this very
day. As will become apparent, except for a single experiment, the neural crest
theory has little or no support when the evolution and development of calcitonin
producing cells in the entire chordate family are considered. Instead, a unifying
origin of all cells of the ultimobranchial bodies reopens questions on the
histogenesis of certain thyroid pathologies previously difficult to explain. On
this aspect, medullary thyroid cancer shows a stronger connection to gut
neuroendocrine tumours than previously recognized. It is envisaged that novel
factors implicated in C cell-derived tumour growth and progression will be
discovered as the mechanisms that regulate lineage expansion of embryonic C cell
precursors from pharyngeal endoderm are uncovered. We will not discuss why C
cells go to the bother of burying themselves in the thyroid - this remains a
mystery.
PMID- 27493882
TI - Familiar Papillary Thyroid Carcinoma in a Large Brazilian Family Is Not
Associated with Succinate Dehydrogenase Defects.
AB - BACKGROUND: Thyroid cancer is the most common endocrine gland malignancy.
Advances in understanding the genetic basis for thyroid cancer revealed the
potential involvement of several genes in the formation of thyroid tumors.
Mutations in the gene coding for succinate dehydrogenase subtype B (SDHB) have
been implicated in papillary thyroid cancer (PTC). Succinate dehydrogenase (SDH)
is a heterotetrameric protein composed of four subunits, SDHA, SDHB, SDHC, and
SDHD, and participates in both the electron transport chain and the tricarboxylic
acid cycle. The aim of the study was to evaluate the association between variants
in the SDHA, SDHB, SDHC, and SDHD genes and familiar PTC in a large Brazilian
family. METHOD: Four patients with PTC, 1 patient with PTC and gastrointestinal
stromal tumor (GIST), 1 patient with GIST, and their relatives - several of them
with different thyroid problems - from a large Brazilian family were screened for
genetic variations of SDHx genes with the use of polymerase chain reaction-single
stranded conformational polymorphism and direct sequencing. RESULTS: Only one
rare variation in SDHA was found in some of the family members, but not
segregating with the disease. No other genetic variants of these genes were
detected in the family members that presented with PTC and/or GIST. CONCLUSION:
Familiar PTC and a GIST were not associated with SDHx mutations; additional
genetic defects, yet unknown, may be responsible for the development of tumor.
PMID- 27493883
TI - Levothyroxine but Not Selenium Increases Endothelial Progenitor Cell Counts in
Patients with Hypothyroidism.
AB - BACKGROUND: Hypothyroidism is a common endocrine disease associated with
increased oxidative stress, increased cardiovascular (CV) risk, CV events and
endothelial dysfunction. Endothelial progenitor cells (EPCs) are a well-known
marker of CV risk. OBJECTIVE: The aim of this work was to ascertain whether
hypothyroidism is associated with lower EPC counts and if treatment with
levothyroxine (LT4) or selenium (Se) improves EPC counts compared to placebo.
METHODS: Hypothyrod patients (n = 100) were randomly divided into five groups to
receive placebo (group A), LT4 (group B) or Se at doses of 83 ug (group C), 166
ug (group D) or 249 ug (group E) for 3 months. Each group comprised 20 patients:
10 with 'mild' hypothyroidism and 10 with 'severe' hypothyroidism. A healthy
control group (group F) with 20 euthyroid subjects was also recruited. Subjects
had to be free of CV disease, diabetes and drugs that interfere with EPCs.
Anthropometric measurements (height, weight, BMI), blood pressure, fasting lipids
and EPC analyses were performed at baseline and after 3 months. RESULTS: EPC
counts were significantly lower in hypothyroid patients compared to controls.
EPCs increased after 3 months of treatment with LT4, but not with Se at any
dosage. CD133+ and CD34+ EPC counts were negatively correlated with thyroid
stimulating hormone (TSH; r (2) = 0.523, p < 0.01 and r (2) = 0.517, p < 0.01,
respectively) and positively correlated with FT4 (r (2) = 0.394, p < 0.01 and r
(2) = 0.369, p < 0.01, respectively). TSH and FT4 were the only predictors of EPC
counts. CONCLUSIONS: Hypothyroidism is associated with low EPC counts. Treatment
with LT4, but not Se, can improve EPC counts.
PMID- 27493884
TI - Comparison of Early Total Thyroidectomy with Antithyroid Treatment in Patients
with Moderate-Severe Graves' Orbitopathy: A Randomized Prospective Trial.
AB - BACKGROUND: The optimal therapeutic choice for Graves' hyperthyroidism in the
presence of moderate-severe Graves' orbitopathy (GO) remains controversial.
OBJECTIVES: We aimed to compare GO course in patients with moderate-severe GO
treated with early total thyroidectomy (TTx) versus antithyroid drug (ATD)
regimens, in a prospective, randomized manner. METHODS: Forty-two patients with
moderate-severe GO were enrolled. A total of 4.5 g of pulse corticosteroids were
given intravenously to all patients before randomization. Patients in the first
group were given TTx, whereas patients in the second group were treated with
ATDs. TSH was kept between 0.4 and 1 mIU/l. The clinical course of GO was
evaluated with proptosis, lid aperture, clinical activity score (CAS), and
diplopia. RESULTS: Eighteen and 24 patients were randomized to the TTx and ATD
groups, respectively. Thyroid autoantibodies decreased significantly, and there
were significant improvements in proptosis, lid aperture, and CAS in the TTx
group. While in the ATD group the decrement in thyroid autoantibodies was not
significant, there were significant improvements in proptosis and CAS. When the
TTx group was compared with the ATD group, anti-TPO, anti-Tg, and TSH-receptor
antibodies were significantly decreased in the TTx group (p < 0.01), but there
was no significant difference with respect to proptosis, lid aperture, CAS, and
diplopia between the two groups during a median (min.-max.) follow-up period of
60 months (36-72). CONCLUSION: Although no definitive conclusions could be drawn
from the study, mainly due to limited power, early TTx and the ATD treatment
regimens, followed by intravenous pulse corticosteroid therapy, seemed to be
equally effective on the course of GO in this relatively small group of patients
with moderate-severe GO during a median (min.-max.) follow-up period of 60 months
(36-72).
PMID- 27493885
TI - A 2015 Italian Survey of Clinical Practice Patterns in the Management of Graves'
Disease: Comparison with European and North American Surveys.
AB - BACKGROUND: Patients suffering from Graves' disease (GD) are quite frequent in
endocrine clinical practice. In particular, overt hyperthyroidism may be
complicated by serious adverse events and requires careful treatment, but its
management has changed over the years in both the USA and European Union (EU).
OBJECTIVES: To evaluate the current diagnosis and management of patient's with GD
in Italy, and compare results with those obtained in previous similar surveys in
the USA and EU. METHODS: Members of the Italian Association of Clinical
Endocrinologists (AME) were asked to participate in a Web-based survey on
management of GD. RESULTS: In total, 947 responses were obtained. The preferred
diagnostic modality in Italy is TSH receptor antibody determination in
conjunction with ultrasound, while radioactive iodine uptake/scan is preferred in
the USA. Methimazole (MMI) 20-30 mg/day with a beta-blocker is the initial
treatment of choice in Italy and the EU, whereas the USA opts more frequently for
radioactive therapy. If Graves' orbitopathy occurs, orbit CT/MRI scans are more
often obtained in Italy and the EU than in the USA. In case of planned pregnancy
in 6-12 months, surgery is more frequently suggested in Italy than in the EU and
USA. Propylthiouracil is generally preferred to MMI in the first trimester.
CONCLUSIONS: Italian endocrinologists have shown significantly different patterns
in diagnosis and management of GD compared to both the USA and EU.
PMID- 27493886
TI - Serum Thyroglobulin Concentration Is a Weak Marker of Iodine Status in a Pregnant
Population with Iodine Deficiency.
AB - OBJECTIVE: To assess the reliability of thyroglobulin (Tg) as a marker of iodine
status during pregnancy. DESIGN: 299 women aged 30.5 +/- 4.8 years (mean +/- SD)
were studied. METHODS: In every subject, we measured urinary iodine concentration
(UIC), serum thyrotropin (TSH), Tg, free thyroxine (fT4), Tg autoantibodies
(TgAbs) and human chorionic gonadotropin (hCG) levels. We excluded samples with
increased TgAbs from the analysis. RESULTS: According to WHO criteria, the study
population was iodine deficient in every trimester. Serum Tg levels did not
differ during the three trimesters of pregnancy. Serum hCG levels fell
significantly as pregnancies advanced. A weak, significantly negative correlation
(limited to the 3rd trimester) was found between Tg and UIC (rho = -0.187, p =
0.039). Serum fT4 decreased as pregnancies advanced and TSH increased. Serum fT4
was negatively correlated with TSH (rho = -0.161, p = 0.006) and positively with
hCG (rho = +0.165, p = 0.005). The multiple regression equation of Tg based on
hCG, TSH, UIC and trimester of pregnancy was significant but weak (F = 4.057, p =
0.003; R(2) = 0.055), with hCG as a significant predictor Tg (p for log hCG =
0.041). CONCLUSIONS: Tg cannot be considered as a valid marker of iodine
deficiency in pregnancy, at least in a mildly iodine-deficient environment.
Further studies in a larger patient cohort with differences in iodine status, as
well as studies on Tg changes after improving iodine status in pregnant women,
are needed in order to corroborate these results.
PMID- 27493887
TI - Obesity Does Not Modify the Risk of Differentiated Thyroid Cancer in a
Cytological Series of Thyroid Nodules.
AB - BACKGROUND: A possible impact of obesity on the risk of thyroid cancer has been
postulated in some studies, but it remains controversial. OBJECTIVE: To
investigate the association between obesity and differentiated thyroid carcinoma
in a population of unselected patients subjected to fine-needle aspiration
cytology (FNAC) for thyroid nodules. METHODS: We retrospectively evaluated the
results of FNAC of thyroid nodules in 4,849 patients (3,809 females and 1,040
males; mean age 55.9 +/- 14.1 years). Patients were stratified according to their
body mass index (BMI). There were 1,876 (38.7%) normal-weight patients (BMI 18
24.9), 1,758 (36.2%) overweight (BMI 25-29.9), 662 (13.7%) grade 1 obese (BMI 30
34.9), 310 (6.4%) grade 2 obese (BMI 35-39.9) and 243 (5.0%) grade 3 obese (BMI
>40). RESULTS: The prevalence of suspicious or malignant nodules (Thy4/Thy5) did
not differ across the 5 BMI groups, i.e. it was 6.8% in normal-weight patients,
6.3% in overweight patients, 6.3% in grade 1 obese patients, 4.0% in grade 2
obese patients and 4.2% in grade 3 obese patients (p = 0.29). The prevalence of
Thy4/Thy5 nodules did not differ when males and females were evaluated separately
(p = 0.22 and p = 0.12, respectively). A significant, lower rate of Thy4/5
cytology was observed in female patients with grade 2-3 obesity (odds ratio 0.51;
95% confidence interval 0.284-0.920; p = 0.009). CONCLUSIONS: The results of this
study, in a retrospective series of patients with thyroid nodules, do not confirm
previous findings reporting an association between obesity and differentiated
thyroid carcinoma. Thus, obese patients with nodular thyroid disease should be
managed the same as normal-weight patients.
PMID- 27493889
TI - Plasma Levels of Free Thyroxine and Risk of Major Bleeding in Bariatric Surgery.
AB - BACKGROUND: In a recent study of patients using vitamin K antagonists, those with
low free thyroxin (FT4) levels within the normal range had a 3- to 5-fold
increased risk of major bleeding. We tested the hypothesis that low levels of
preoperative FT4 within the reference range are associated with an increased risk
of major bleeding during and after bariatric surgery. METHODS: The charts of
2,872 consecutive patients undergoing bariatric surgery were retrospectively
screened for bleeding episodes. Patients with major bleeding until 1 month after
surgery were compared to randomly selected control patients without bleeding, in
a ratio of 1:4. We evaluated the association between preoperative FT4 levels and
the risk of major bleeding by logistic regression. RESULTS: Seventy-two cases
(2.5%) with major bleeding were identified and 288 controls were selected. The
median plasma level of FT4 was 13 pmol/l (interquartile range: 12-14) in the
cases as well as in the controls. No clear effect was observed of low levels of
FT4 on the risk of major bleeding: odds ratio 1.48 (95% CI: 0.46-4.80) for
patients with an FT4 level <11 pmol/l, 1.03 (0.49-2.18) for patients with an FT4
level <12 pmol/l, and 1.12 (0.65-1.94) for patients with an FT4 level <13 pmol/l
as compared to patients with FT4 values greater than or equal to these cutoff
levels. INTERPRETATION: We did not observe an increased risk of major bleeding
with low levels of FT4 in patients undergoing bariatric surgery.
PMID- 27493888
TI - Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled
Analysis of Two Case-Control Studies.
AB - PURPOSE: Physical activity has been hypothesized to influence cancer occurrence
through several mechanisms. To date, its relation with thyroid cancer risk has
been examined in relatively few studies. We pooled 2 case-control studies
conducted in Cuba and Eastern France to assess the relationship between self
reported practice of recreational physical activity since childhood and thyroid
cancer risk. METHODS: This pooled study included 1,008 cases of differentiated
thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years
in the French and Cuban studies, respectively). Risk factors associated with the
practice of recreational physical activity were estimated using OR and 95% CI.
Logistic regressions were stratified by age class, country, and gender and were
adjusted for ethnic group, level of education, number of pregnancies for women,
height, BMI, and smoking status. RESULTS: Overall, the risk of thyroid cancer was
slightly reduced among subjects who reported recreational physical activity (OR =
0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more
relevant than the duration (years). CONCLUSION: Long-term recreational physical
activity, practiced since childhood, may reduce the DTC risk. However, the
mechanisms whereby the DTC risk decreases are not yet entirely clear.
PMID- 27493890
TI - Iodide Transport Defect and Breast Milk Iodine.
AB - BACKGROUND: Iodide transport defect (ITD) is a dyshormonogenetic congenital
hypothyroidism caused by sodium/iodide symporter (NIS) gene mutations. In the
lactating mammary gland, iodide is concentrated by NIS, and iodine for thyroid
hormone synthesis is thereby supplied to the infant in the breast milk. CASE
DESCRIPTION: A 34-year-old Japanese woman was diagnosed with ITD caused by a
homozygous NIS gene mutation T354P. She had begun treatment of primary
hypothyroidism with levothyroxine at the age of 5. She delivered a baby at the
age of 36. The iodine concentration in her breast milk was 54 ug/l. She took a 50
mg potassium iodide tablet daily to supply iodine in the breast milk, starting on
the 5th day postpartum. Her breast milk iodine concentration increased to 90 ug/l
(slightly above the minimum requirement level). The patient weaned her baby and
stopped taking the daily potassium iodide tablet 6 weeks postpartum, and the baby
began to be fed with relatively iodine-rich formula milk. The baby's thyroid
function remained normal from birth until 6 months of age. CONCLUSION: Possible
iodine deficiency in the infant breast-fed by an ITD patient should be kept in
mind. Prophylactic iodine supplementation is essential for such infants in order
to prevent severe iodine deficiency.
PMID- 27493891
TI - Risk of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Who Achieved
Sustained Virological Response.
PMID- 27493892
TI - Consensus for Radiotherapy in Hepatocellular Carcinoma from The 5th Asia-Pacific
Primary Liver Cancer Expert Meeting (APPLE 2014): Current Practice and Future
Clinical Trials.
AB - A consensus meeting to develop practice guidelines and to recommend future
clinical trials for radiation therapy (RT), including external beam RT (EBRT),
and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at
the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert
consortium. Although there is no randomized phase III trial evidence, the
efficacy and safety of RT in HCC has been shown by prospective and retrospective
studies using modern RT techniques. Based on these results, the committee came to
a consensus on the utility and efficacy of RT in the management of HCC according
to each disease stage as follows: in early and intermediate stage HCC, if
standard treatment is not compatible, RT, including EBRT and SIRT can be
considered. In locally advanced stage HCC, combined EBRT with transarterial
chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be
considered. In terminal stage HCC, EBRT can be considered for palliation of
symptoms and reduction of morbidity caused by the primary tumor or its
metastases. Despite the currently reported benefits of RT in HCC, the committee
agreed that there is a compelling need for large prospective studies, including
randomized phase III trial evidence evaluating the role of RT. Specifically
studies evaluating the efficacy and safety of sequential combination of EBRT and
SIRT are strongly recommended.
PMID- 27493893
TI - Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with
Advanced Liver Cirrhosis.
AB - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) with decompensated liver
cirrhosis (LC) is a life-threatening condition, which is amenable to liver
transplantation (LT) as the standard first-line treatment. However, the
application of LT can be limited due to a shortage of donor livers. This study
aimed to clarify the effect of non-surgical therapy on the survival of patients
with HCC and decompensated LC. METHODS: Of the 58,886 patients with HCC
registered in the nationwide survey of the Liver Cancer Study Group of Japan
(January 2000-December 2005), we included 1,344 patients with primary HCC and
Child-Pugh (C-P) grade C for analysis in this retrospective study. Among the
patients analyzed, 108 underwent LT, 273 were treated by local ablation therapy
(LAT), 370 were treated by transarterial chemoembolization (TACE), and 593
received best supportive care (BSC). The effect of LT, LAT, and TACE on overall
survival (OS) was analyzed using multivariate and propensity score analyses.
RESULTS: Patient characteristics did not differ significantly between each
treatment group and the BSC group, after propensity score matching. LAT (hazard
ratio [HR]) =0.568; 95% confidence interval [CI], 0.40-0.80) and TACE (HR=0.691;
95% CI, 0.50-0.96) were identified as significant contributors to OS if the C-P
score was less than 11 and tumor conditions met the Milan criteria. CONCLUSIONS:
For patients with HCC within the Milan criteria and with a C-P score of 10 or 11,
locoregional treatment can be used as a salvage treatment if LT is not feasible.
PMID- 27493894
TI - Survival Analysis over 28 Years of 173,378 Patients with Hepatocellular Carcinoma
in Japan.
AB - BACKGROUND: Beginning in 1967, the Liver Cancer Study Group of Japan (LCSGJ)
started a nationwide prospective registry of all patients with hepatocellular
carcinoma (HCC) diagnosed at more than 700 institutions. To determine the
effectiveness of surveillance and treatment methods longitudinally, we analyzed
improvements over time in overall survival (OS) of 173,378 patients with HCC
prospectively entered into the LCSGJ registry between 1978 and 2005. METHODS: All
patients from more than 700 institutions throughout Japan with HCC were entered
into the LCSGJ registry. Patients were grouped by years of diagnosis, with OS and
5-year OS rates being calculated. We also assessed OS and 5-year OS rates in
patients who underwent resection, local ablation, transarterial chemoembolization
(TACE), and hepatic arterial infusion chemotherapy (HAIC) and in those with
baseline serum alpha-fetoprotein (AFP) levels >=400 ng/ml. RESULTS: The 5- and 10
year OS rates in the cohort of 173,378 patients were 37.9% and 16.5%,
respectively. However, over time, the mean maximum tumor size decreased
significantly, whereas 5-year OS rates and median survival time increased
significantly. Similar findings were observed separately in patients who
underwent resection, local ablation, TACE, and HAIC, as well as in patients with
AFP levels >=400 ng/ml. CONCLUSION: The establishment of a nationwide HCC
surveillance program in Japan has contributed to longer median OS and increased
OS rates in patients diagnosed with this disease. These findings suggest that the
establishment of a surveillance program in other countries with patients at risk
for HCC may provide significant survival benefits.
PMID- 27493896
TI - How to Improve Therapeutic Ratio in Radiotherapy of HCC.
AB - BACKGROUND: During the past two decades, external-beam radiation technology has
substantially changed from traditional two-dimensional to conformal three
dimensional to intensity-modulated planning and stereotactic body radiotherapy
(SBRT). SUMMARY: Modern techniques of radiotherapy (RT) are highly focused and
capable of delivering an ablative dose to targeted hepatocellular carcinoma (HCC)
tumors. SBRT is an option for selected patients with limited tumor volume and non
eligibility for other invasive treatments. Moreover, RT combined with a radiation
sensitizer (RS) to increase the therapeutic ratio has shown promising results in
select studies, prompting further investigation of this combination. With the
undetermined role of RT in treatment guidelines and variation in patterns of
treatment failure after RT in patient with HCC, useful biomarkers to guide RT
decision-making and selection of patients are needed and emerging. KEY MESSAGE:
The objective of this review is to summarize the current RS with SBRT schemes and
biomarkers for patient selection used to maximize the effect of RT on HCC.
PMID- 27493895
TI - Liver-Directed Radiotherapy for Hepatocellular Carcinoma.
AB - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) continues to increase
world-wide. Many patients present with advanced disease with extensive local
tumor or vascular invasion and are not candidates for traditionally curative
therapies such as orthotopic liver transplantation (OLT) or resection.
Radiotherapy (RT) was historically limited by its inability to deliver a
tumoricidal dose; however, modern RT techniques have prompted renewed interest in
the use of liver-directed RT to treat patients with primary hepatic malignancies.
SUMMARY: The aim of this review was to discuss the use of external beam RT in the
treatment of HCC, with particular focus on the use of stereotactic body
radiotherapy (SBRT). We review the intricacies of SBRT treatment planning and
delivery. Liver-directed RT involves accurate target identification, precise and
reproducible patient immobilization, and assessment of target and organ motion.
We also summarize the published data on liver-directed RT, and demonstrate that
it is associated with excellent local control and survival rates, particularly in
patients who are not candidates for OLT or resection. KEY MESSAGES: Modern liver
directed RT is safe and effective for the treatment of HCC, particularly in
patients who are not candidates for OLT or resection. Liver-directed RT,
including SBRT, depends on accurate target identification, precise and
reproducible patient immobilization, and assessment of target and organ motion.
Further prospective studies are needed to fully delineate the role of liver
directed RT in the treatment of HCC.
PMID- 27493897
TI - Personalized Clinical Trials in Hepatocellular Carcinoma Based on Biomarker
Selection.
AB - BACKGROUND: Since the approval of sorafenib there have been numerous failures of
new agents in Phase III studies for treatment of advanced hepatocellular
carcinoma (HCC). These studies have generally ignored the molecular heterogeneity
of HCC and they have not enrolled patients based on predictive markers of
response. The development of molecular targeted therapeutics in HCC needs to
model the approach that has been taken with great success in other solid tumors,
to decrease the likelihood of failure in future studies. SUMMARY: Here we review
the paradigm taken with novel targeted agents in other solid tumors and highlight
ongoing studies in HCC that are incorporating biomarkers in clinical development.
KEY MESSAGES: With the appreciation of the molecular diversity of HCC, clinical
development of new agents in HCC will need to be targeted towards those patients
who are most likely to benefit. This strategy, based on biomarkers for patient
selection, is more likely to yield positive results and mitigate the risk of
continued negative Phase III studies.
PMID- 27493898
TI - Anatomical and Functional Estimations of Brachial Artery Diameter and Elasticity
Using Oscillometric Measurements with a Quantitative Approach.
AB - Noninvasive vascular function measurement plays an important role in detecting
early stages of atherosclerosis and in evaluating therapeutic responses. In this
regard, recently, new vascular function measurements have been developed. These
new measurements have been used to evaluate vascular function in coronary
arteries, large aortic arteries, or peripheral arteries. Increasing vascular
diameter represents vascular remodeling related to atherosclerosis. Attenuated
vascular elasticity may be a reliable marker for atherosclerotic risk assessment.
However, previous measurements for vascular diameter and vascular elasticity have
been complex, operator-dependent, or invasive. Therefore, simple and reliable
approaches have been sought. We recently developed a new automated oscillometric
method to measure the estimated area (eA) of a brachial artery and its volume
elastic modulus (VE). In this review, we further report on this new measurement
and other vascular measurements. We report on the reliability of the new
automated oscillometric measurement of eA and VE. Based on our findings, this
measurement technique should be a reliable approach, and this modality may have
practical application to automatically assess muscular artery diameter and
elasticity in clinical or epidemiological settings. In this review, we report the
characteristics of our new oscillometric measurements and other related vascular
function measurements.
PMID- 27493899
TI - Assessment of Arterial Stiffness Using the Cardio-Ankle Vascular Index.
AB - BACKGROUND: Arterial stiffness is an independent predictor of outcomes for
patients with cardiovascular disease. Although measurement of pulse wave velocity
is a widely accepted, noninvasive approach for the assessment of arterial
stiffness, its accuracy is affected by changes in blood pressure. SUMMARY: The
cardio-ankle vascular index (CAVI) is an index of the overall stiffness of the
artery from the origin of the aorta to the ankle and is theoretically independent
of blood pressure at the time of measurement. CAVI increases linearly with age
and is elevated even in mild arteriosclerotic disease. It can identify
differences in the degree of arteriosclerosis among patients with severe
arteriosclerotic disease and better reflects the severity of disease of the
coronary artery than does brachial-ankle pulse wave velocity. Patients with
higher CAVI values show a poor prognosis compared with those with lower CAVI
values. Furthermore, CAVI can be lowered by controlling diabetes mellitus and
hypertension. KEY MESSAGES: The primary aims of assessing arterial stiffness
using CAVI are to assist in the early detection of arteriosclerosis, allowing
timely treatment and lifestyle modification, and to quantitatively evaluate the
progression of disease and the effectiveness of treatment. Whether CAVI-guided
therapy can improve prognosis in high-risk patients needs to be further examined
to confirm the clinical usefulness of this measure.
PMID- 27493900
TI - Carotid Stiffness: A Novel Cerebrovascular Disease Risk Factor.
AB - Carotid stiffening is considered an important element in the pathogenesis of
cerebrovascular diseases. These include stroke as well as vascular dementia and
depression. However, results of individual studies evaluating the association
between carotid stiffening and incident stroke have been inconsistent. Therefore,
we have conducted a systematic review and meta-analysis, showing that carotid
stiffening is associated with incident stroke independently of cardiovascular
risk factors and aortic stiffness. In addition, carotid stiffening improved
stroke risk prediction beyond the Framingham stroke risk factors and aortic
stiffness. Other studies have shown that carotid stiffening is associated with a
higher incidence of vascular dementia and depressive symptoms. This suggests that
carotid stiffness is a potential separate target for prevention strategies of
cerebrovascular disease.
PMID- 27493901
TI - Relation of Habitual Chocolate Consumption to Arterial Stiffness in a Community
Based Sample: Preliminary Findings.
AB - BACKGROUND: The consumption of chocolate and cocoa has established cardiovascular
benefits. Less is known about the effects of chocolate on arterial stiffness, a
marker of subclinical cardiovascular disease. The aim of this study was to
investigate whether chocolate intakes are independently associated with pulse
wave velocity (PWV), after adjustment for cardiovascular, lifestyle and dietary
factors. METHODS: Prospective analyses were undertaken on 508 community-dwelling
participants (mean age 61 years, 60% women) from the Maine-Syracuse Longitudinal
Study (MSLS). Habitual chocolate intakes, measured using a food frequency
questionnaire, were related to PWV, measured approximately 5 years later.
RESULTS: Chocolate intake was significantly associated with PWV in a non-linear
fashion with the highest levels of PWV in those who never or rarely ate chocolate
and lowest levels in those who consumed chocolate once a week. This pattern of
results remained and was not attenuated after multivariate adjustment for
diabetes, cardiovascular risk factors and dietary variables (p = 0.002).
CONCLUSIONS: Weekly chocolate intake may be of benefit to arterial stiffness.
Further studies are needed to explore the underlying mechanisms that may mediate
the observed effects of habitual chocolate consumption on arterial stiffness.
PMID- 27493902
TI - Within-Home Blood Pressure Variability on a Single Occasion Has Clinical
Significance.
AB - There is growing evidence that diversely defined blood pressure variability (BPV)
is an independent predictor of hypertensive target organ damage (TOD) and
cardiovascular events. Several mechanisms have been speculated to underlie
episodes of increased BPV, including the impairment of autonomic or hormonal
regulation, renal dysfunction, and increased arterial stiffness. Within-home BPV,
defined as differences in BP values obtained on a single occasion at home, could
have prognostic significance for hypertensive TOD. It is typically thought that
BP values are decreased with repeated measurements on a single occasion at home,
but in the present subanalysis of 4,149 J-HOP (Japan Morning Surge-Home Blood
Pressure) study patients, approximately 20% of the patients' home BP values were
increased or unchanged by repeated measurements on a single occasion. In
addition, those patients were likely to have hypertensive TOD. Thus, home BP
measurement should be taken twice or more to detect the increase trend in home
BP, which has been defined as within-home BPV.
PMID- 27493903
TI - Molecular Mechanisms of Arterial Stiffening.
AB - Stiffening of large arteries is a hallmark of vascular aging and one of the most
important determinants of the age-related increase in blood pressure and
cardiovascular disease events. Despite a substantial genetic component, the
molecular mechanisms underlying phenotypic variability in arterial stiffness
remain unknown. Previous genetic studies have identified several genetic variants
that are associated with measures of arterial stiffness. Here, we review the
relevant advances in the identification of pathways underlying arterial stiffness
from genomic studies.
PMID- 27493904
TI - The J-Curve Phenomenon in Hypertension.
AB - Almost immediately after antihypertensive therapy was proven effective in
preventing cardiovascular events, the J-curve issue emerged as a hot topic. The
Hypertension Optimal Treatment (HOT) trial attempted to address this question
(diastolic blood pressure <80, <85, and <90 mm Hg) but ended up with a post hoc
analysis indicating a nadir of 138.5 mm Hg systolic and 82.6 mm Hg diastolic
blood pressure. Nevertheless, this observational finding was supported by the
results of observational studies in the general population and by post hoc
analyses of antihypertensive treatment trials. The currently ongoing Systolic
Hypertension Optimal Treatment (SHOT) trial investigates whether the relationship
between systolic blood pressure and stroke recurrence is linear or J-shaped by
treating systolic blood pressure to <125, <135, and <145 mm Hg in patients with a
history of recent stroke. This trial may provide additional but probably
inconclusive evidence, because optimal blood pressure might differ between
individuals and across outcomes. Nevertheless, a universal beneficial, instead of
optimal, level of blood pressure for antihypertensive treatment may exist
approximating 130/80 mm Hg and should be investigated by comparing 130/80 mm Hg
with 140/90 mm Hg as a target blood pressure in hypertensive patients with the
simultaneous use of modern blood pressure measuring techniques, such as home and
ambulatory blood pressure monitoring.
PMID- 27493905
TI - The effect of low dose fentanyl as a premedication before induction of general
anesthesia on the neonatal apgar score in cesarean section delivery: randomized,
double-blind controlled trial.
AB - BACKGROUND: The administration of opioids before induction of general anesthesia
can be considered as a problem in cesarean section. The aim of this study was to
compare the effects of intravenous Fentanyl as a premedication before induction
of general anesthesia versus placebo on maternal hemodynamic parameters and on
the first and fifth minutes Apgar score in the neonates in elective cesarean
delivery. METHODS: This double- blinded, randomized, clinical trial study was
conducted in 2014-2015 at Vali-e-Asr hospital, Birjand, Iran. Ninety full term
pregnant women undergoing elective cesarean section delivery under general
anesthesia were selected. The participants were randomly classified into two
groups: The Fentanyl group and the placebo. Iintravenous Fentanyl 1MUg/kg was
administrated three minutes before anesthesia induction for the Fentanyl group,
and 2 milliliter normal saline was administered for the placebo group. Maternal
mean arterial pressure, heart rate before the start of anesthesia induction and
thirty seconds after intubation were measured. Also, the first and fifth minutes
Apgar scores of the neonates were evaluated and recorded by a blinded
anesthesiologist. The clinical trial registration number was IRCT2015010320112N3.
RESULTS: Maternal mean arterial pressure was significantly lower in the Fentanyl
group than the placebo group after intubation. Heart rate was significantly
higher in the placebo group before the start of anesthesia induction and after
intubation compared to the Fentanyl group. The first and fifth minutes' Apgar
scores of the neonates were not statistically different between the two groups.
CONCLUSION: Administration of 1MUg/Kg intravenous Fentanyl before the induction
of anesthesia for cesarean section delivery decreases maternal hemodynamic
changes after intubation. In addition, it does not have any effect on Apgar
scores of the neonate in the 1st and 5th minutes after birth.
PMID- 27493906
TI - Do ethical considerations influence any in HTA reports? A review of reports.
AB - BACKGROUND: Dealing with ethical considerations is a major component of Health
Technology Assessment (HTA) definitions. OBJECTIVES: Present study aimed to
explore and describe the manner of ethical analyses in HTA reports and the
effects it had on HTA-related decision making around the world. METHODS: By
considering the contextual milieu of reports and searching for ethical themes and
subjects in HTA full reports, a descriptive analysis of HTA reports' contents and
related processes was conducted. The review focused on all English HTA reports
issued in a year. All ethical aspects, criteria, approaches, and also decision-
making related ethical issues were described and summarized in retrieved reports.
The inclusion of ethical aspects in final decision-making criteria of HTA reports
was also considered. RESULTS: Eighty-nine HTA reports issued in one year were
included in this review and analyzed for ethical considerations. There was no
trace of any ethical issues in 60.7% of retrieved HTA reports. Dimensions of
equity in resource distribution, stakeholder engagement, social values, essence
and nature of technology, and ethical issues about the method of assessment for
decision making, and physician-patient relationship were raised and discussed in
38.2%, 3.4%, 3.4%, 3.4%, 34.8% and 3.4% of reports respectively. Those issues
were also included in 44.1, 5.9, 2.9, 2.9, 0 and 2.9% of final reports,
respectively. In overall, only in 16 cases (17.9%) of all 89 reports, ethical
issues were included in HTA decision-making orientations. CONCLUSION: This review
shows that ethical issues are occasionally raised and discussed in HTA reports.
More importantly, the inclusion of ethical concerns as a decision criterion in
HTAs is few and insufficient.
PMID- 27493907
TI - Is the serum ferritin level a considerable predictor for hemorrhagic
transformation of ischemic stroke?
AB - BACKGROUND: Hemorrhagic Transformation (HT) of Ischemic Stroke (IS) is a
detrimental complication. This study investigated the association between serum
ferritin level and HT in patients with massive IS of middle cerebral artery.
METHODS: Thirty patients with massive IS of middle cerebral artery were enrolled
in this prospective cohort study. They were divided into two groups based on the
serum ferritin level, lower or greater than 164.1ng/ml at the first 24 hours
after admission. To investigate the incidence of HT in the two groups, we
observed them for two weeks. RESULTS: During the two- week observation, the
incidence of HT was two persons (13.3%) in the group with the serum ferritin
level of lower than 164.1ng/ml, and eight persons (53.3%) in the other group.
This difference was statistically significant between the two groups (p=0.02).
The relative risk of HT was 4 (95% CI: 1.012- 15.8) in the patients with massive
IS of middle cerebral artery and the serum ferritin level greater than
164.1ng/ml. CONCLUSION: This study revealed that the serum ferritin level greater
than 164.1ng/ml in the first 24 hours after admission is a reasonably important
predictor for HT of IS. Conducting studies on factors affecting the serum
ferritin level are suggested.
PMID- 27493908
TI - Comparing nurses' knowledge retention following electronic continuous education
and educational booklet: a controlled trial study.
AB - BACKGROUND: Training methods that enhance nurses' learning and retention will
increase the quality of patient care. This study aimed to compare the
effectiveness of electronic learning and educational booklet on the nurses'
retention of diabetes updates. METHODS: In this controlled trial study,
convenience sampling was used to select 123 nurses from the endocrinology and
internal medicine wards of three hospitals affiliated to Tehran University of
Medical Sciences (Tehran, Iran). The participants were allocated to three groups
of manual, electronic learning, and control. The booklet and electronic learning
groups were trained using educational booklet and electronic continuous medical
education (CME) website, respectively. The control group did not receive any
intervention. In all the three groups, the nurses' knowledge was measured before
the intervention, and one and four weeks after the intervention. Data were
collected by a questionnaire. RESULTS: Significant differences were observed
between the mean scores of the three groups one and four weeks after the
intervention (F=26.17, p=0.001 and F=4.07, p=0.020, respectively), and post hoc
test showed that this difference was due to the higher score in e-learning group.
Both e-learning and booklet methods could effectively improve nurses' knowledge
(chi2=23.03, p=0.001 and chi2=51.71, p=0.001, respectively). CONCLUSION:
According to the results of this study, electronic learning was more effective
than booklet in enhancing the learning and retention of knowledge. Electronic
learning is suggested as a more suitable method as it provides appropriate
interactions and attractive virtual environments to motivate the learners and
promote retention.
PMID- 27493909
TI - A review on laboratory tests' utilization: A trigger for cutting costs and
quality improvement in health care settings.
AB - BACKGROUND: Considering the role of laboratory tests as a central part of
controlling health expenditure, this study intends to investigate laboratory
tests overutilization in Iran to pave the way for future interventions. METHODS:
Inappropriate laboratory utilization was reviewed in a cross-sectional survey
through the retrospective analysis of 384 medical records at a tertiary center.
To pave the way for future intervention, overutilization tests were classified
into two categories, inappropriate and inefficient, and then they were analyzed.
Frequency analysis was used to analysis patient's age, gender, hospital wards,
length of stay, and diagnosis as well as inappropriate test and inefficient
tests. RESULTS: A total of 143 (1.50 %) of the tests were inefficient and was
ordered due to laboratory errors including hemolysis, inefficient sampling, or
absurd results. 2522 (26.40%) of the tests were inappropriate and stem from
failure to meet medical/clinical appropriateness criteria. CONCLUSION: Whereas,
inappropriate test ordering was more frequent than inefficient tests, the initial
improvement strategy should focus on physicians' test ordering behavior through
conducting proper teaching strategies, ongoing audit and educational feedback,
implementing health information technology tools and employing laboratory
practice guidelines (LPGs) and testing algorithms. Conducting continuous quality
improvement cycle for laboratory services and training of personnel involved in
blood sampling is recommended for inefficient tests.
PMID- 27493910
TI - The effectiveness of FOBT vs. FIT: A meta-analysis on colorectal cancer screening
test.
AB - BACKGROUND: After lung and prostate cancers, colorectal cancer (CRC) is the third
most common cancer in men and the second most common cancer in women after breast
cancer worldwide. Every year, more than one million people are diagnosed with
colorectal cancer worldwide and half of these patients die from this disease,
making it the fourth leading cause of death in the world. This systematic review
aimed to assess the effectiveness of the two colorectal diagnostic tests of FOBT
(fecal occult blood test) and FIT (fecal immunochemical test)) in terms of
technical performance. METHODS: To retrieve the relevant evidence, appropriate
medical databases such as Cochrane library, NHSEED, Scopus and Google scholar
were searched from February 2013 to July 2014, using free-texts and Mesh. In this
study, inclusion/exclusion criteria of the papers, randomized controlled trials,
economic evaluations, systematic reviews, meta-analyses and meta-syntheses of the
effectiveness of FIT versus FOBT tests in moderate-risk populations (age: 50 to
70 years), which had reported the least of such outcomes as sensitivity,
specificity and clinical outcomes were reviewed. The analyses of the
effectiveness outcomes were performed in the form of meta-analysis. RESULTS: Five
papers were eligible to be included in the final phase of the study for
synthesis. FIT showed a better performance in participation and positivity rate.
Moreover, in terms of false positive and negative rate, FIT showed fewer rates
compared to FOBT (RR:-4.06; 95% CI (-7.89-0.24), and NN-scope (Number need to
scope) (2.2% vs. 1.6%), and NN-screen (Number need to screen) (84% vs. 31-49% in
different cut off levels) showed significant differences in FOBT vs. FIT,
respectively. CONCLUSION: In the five included studies (3, 11-14), the
acceptability of FIT was more than FOBT. However, in our meta-analysis, no
difference was found between the two tests. FIT was significant in positivity
rate and had a better performance in participation rate, and a fewer false
negative numbers compared to FOBT.
PMID- 27493911
TI - Radioprotective effects of selenium and vitamin-E against 6MV X-rays in human
blood lymphocytes by micronucleus assay.
AB - BACKGROUND: Critical macromolecules of cells such as DNA are in exposure to
damage of free radicals that induced from the interaction of ionizing radiation
with biological systems. Selenium and vitamin-E are natural compounds that have
been shown to be a direct free radical scavenger. The aim of this study was to
investigate the radioprotective effect of selenium and vitamin-E separately and
synergistically against genotoxicity induced by 6MV x-rays irradiation in blood
lymphocytes. METHODS: Fifteen volunteers were divided into three groups include
A, B and C. These groups were given selenium (800IU), vitamin-E (100mg) and
selenium (400IU) + vitamin-E (50mg), respectively. Peripheral blood samples were
collected from each group before (0hr) and 1, 2 and 3hr after selenium and
vitamin-E administration (separately and synergistically). Then the blood samples
were irradiated to 200cGy of 6MV x-rays. After that lymphocyte samples were
cultured with mitogenic stimulation to determine the chromosomal aberrations with
micronucleus assay in cytokinesis-blocked binucleated cells. RESULTS: The
lymphocytes in the blood samples collected at one hr after ingestion selenium and
vitamin-E, exposed in vitro to x-rays exhibited a significant decrease in the
incidence of micronuclei, compared with control group at 0hr. The maximum
protection and decrease in frequency of micronuclei (50%) were observed at one hr
after administration of selenium and vitamin-E synergistically. CONCLUSION: The
data suggest that ingestion of selenium and vitamin-E as a radioprotector
substance before exposures may reduce genetic damage caused by x-rays
irradiation.
PMID- 27493912
TI - Determinants of adherence to self-care behavior among women with type 2 diabetes:
an explanation based on health belief model.
AB - BACKGROUND: Self-care is an essential element in treating a person with diabetes;
and managing diabetes is of prime importance. The aim of this study was to
investigate the predictors of adherence to self-care behavior among women with
Type 2 diabetes. METHODS: This cross-sectional study was conducted on 210 female
patients aged 30 to 60. Data collection tool was an anonymous valid and reliable
questionnaire designed based on the Health Belief Model (HBM), which acquired
information about the followings: Perceived susceptibility, severity, benefits,
barriers, self-efficacy and diabetes self-care behavior. Data were analyzed by t
test, chisquare and regression analysis. RESULTS: The multiple regression models
revealed 59.9% of the variance of self-care behavior with self-efficacy,
perceived barrier, benefit and susceptibility. Additionally, the highest weight
for beta (beta=0.87) was found for self-efficacy. Self-care behavior was
positively correlated with all HBM variables except for perceived barriers
showing a negative correlation. CONCLUSION: The Health Belief Model may be used
as a framework to design intervention programs in an attempt to improve adherence
to self-care behaviors of women with diabetes. In addition, the results indicated
that self-efficacy might play a more crucial role in developing self-care
behaviors than t other HBM components. Therefore, if the focus is placed on self
efficacy when developing educational programs, it may increase the likelihood of
adherence to self-care behavior.
PMID- 27493913
TI - The importance of BRCA1 and BRCA2 genes mutations in breast cancer development.
AB - Many factors including genetic, environmental, and acquired are involved in
breast cancer development across various societies. Among all of these factors in
families with a history of breast cancer throughout several generations,
genetics, like predisposing genes to develop this disease, should be considered
more. Early detection of mutation carriers in these genes, in turn, can play an
important role in its prevention. Because this disease has a high prevalence in
half of the global population, female screening of reported mutations in
predisposing genes, which have been seen in breast cancer patients, seems
necessary. In this review, a number of mutations in two predisposing genes (BRCA1
and BRCA2) that occurred in patients with a family history was investigated. We
studied published articles about mutations in genes predisposed to breast cancer
between 2000 and 2015. We then summarized and classified reported mutations in
these two genes to recommend some exons which have a high potential to mutate.
According to previous studies, exons have been reported as most mutated exons
presented in this article. Considering the large size and high cost of screening
all exons in these two genes in patients with a family history, especially in
developing countries, the results of this review article can be beneficial and
helpful in the selection of exon to screen for patients with this disease.
PMID- 27493914
TI - High frequency of metabolic syndrome in adult Zoroastrians in Yazd, Iran: a cross
sectional study.
AB - BACKGROUND: Metabolic syndrome (MS) is a cluster of metabolic disturbances, and
its prevalence is increasing worldwide. MS exhibits variations among ethnic
groups. Zoroastrianism is an ethnic minority which has maintained its isolation
and endogamy up to now. So, we evaluated the frequency of MS in Zoroastrians of
Yazd, Iran. METHODS: In this cross-sectional study, participants aged >=30 years
were selected using a systematic random sampling. Weight, height, body mass index
(BMI), waist circumference (WC), hip circumference (HC), waistto- hip ratio (WHR)
and blood pressure (BP) were measured using standard methods. Also, blood levels
of glucose, triglycerides (TG), total cholesterol, high-density lipoprotein
(HDL), low-density lipoprotein (LDL), urea, creatinine and uric acid (UA) were
measured. Both revised National Cholesterol Education Program Adult Treatment
Panel III (ATPIII) and Joint Interim Statement (JIS) criteria were used to
diagnose the MS. RESULTS: The mean+/-SD age of the participants (n=403) was
56.9+/-12.8 years. The frequency of MS was 69.7% and 74.9% based on JIS and
ATPIII criteria, respectively; this was significantly different by age, marital
status, job, educational level, and menopausal status (p<0.05). The most
prevalent abnormal parameters of MS according to ATPIII and JIS criteria were
high WC (95%) and low HDL (87.9%), respectively. Mean LDL, systolic BP, WHR, UA,
urea, and creatinine were different between men and women. The difference between
the age groups was statistically significant for BMI, systolic BP, diastolic BP,
TG, WHR and urea (p<0.05). CONCLUSION: This study showed a high frequency of MS
in Zoroastrians of Yazd, Iran.
PMID- 27493916
TI - Application of ultrasound in pulseless electrical activity (PEA) cardiac arrest.
PMID- 27493915
TI - Outcomes of assisted reproduction treatment after dopamine agonist -cabergoline-
for prevention of ovarian hyper stimulation syndrome.
AB - BACKGROUND: Release of vascular endothelial growth factor (VEGF) by ovaries in
response to HCG administration is one of the main mechanisms of ovarian hyper
stimulation syndrome. Since Dopamine/dopamine receptor2 (Dp-r2) pathway activity
mediated by VEGF/ Vascular endothelial growth factor receptor 2 (VEGFR- 2)
signaling-, is associated with angiogenic events, dopamine agonists were used for
the management of severe forms of OHSS. In order to assess the effects of
Cabergoline on angiogenesis in the human endometrium, and subsequently its
impacts on the implantation rate this study was conducted. METHODS: This
historical cohort study was conducted based on existing data of 115 patients (20
40 years) whom underwent assisted reproductive treatment (ART) and with a high
probability for developing OHSS between March 2007 and September 2008. Forty five
cases received Cabergoline were compared to 70 control subjects. The statistical
methods used were: Unpaired t-test for continuous variables and the chi-square
test (or Fisher's exact test if required) for categorical variables. RESULTS:
None of the patients (treatment or control group) developed OHSS. The etiologies
of infertility and administration of GnRH agonist or antagonist protocols were
similar in two groups (p>0.2). Number of transferred embryos and zygote intra
fallopian transfer (ZIFT) did not differ between the two groups (p>=0.06).
Implantation rate in treatment (3.1%) and control (6.6%) subjects was similar
(p=0.4). No significant difference was observed in fertilization rate, chemical,
clinical and ongoing pregnancies between the two groups (p>0.5). CONCLUSION:
Cabergoline can be safely administered in ART protocols to prevent OHSS, without
compromising ART outcomes.
PMID- 27493918
TI - Length and weight growth trends for children less than two years old in Zanjan,
Iran: Longitudinal modeling.
AB - BACKGROUND: Growth failure in children less than five years old can lead to the
serious complications such as increased mortality, learning difficulties or
physical disability. The aim of this study was to investigate the nonorganic
factors affecting the growth trend in less than two years children living in
Zanjan, Iran. METHODS: This longitudinal study was conducted on a sample of 3566
children less than two years old in Zanjan. Weight and length growth trends were
recorded as ordinal variables and analyzed by longitudinal marginal model.
RESULTS: About 12% (n=289) and 8% (n=212) of children had at least one
decline/stagnation in the weight and length growth curve, respectively. Based on
the marginal model, the effect of the child's age and residence area on the
weight and length growth trends were statistically significant (p<0.05).
CONCLUSION: Given the relatively high prevalence of growth failure among studied
children less than two years old in rural areas of Zanjan, raising the awareness
of parents in rural areas about feeding and nutritional behaviors of children
seems an important issue. Additionally, healthcare providers should mostly focus
on monitoring the growth of children older than 12 months.
PMID- 27493917
TI - Combined effect of botulinum toxin and splinting on motor components and function
of people suffering a stroke.
AB - BACKGROUND: Spasticity is one of the problems after a stroke. Due to this
increase in muscle tone, patients are confronted with problems in motor control
and difficulties in activities of daily living and complications such as
shortness and contracture. The aim of this study was to examine the effects of
the simultaneous use of both splint and botulinum toxin-A (BTX-A) injection on
spasticity, range of motion and upper extremity function in a 3-month period.
METHODS: In this study a comparison was done between three groups of
interventions, conducted in rehabilitation clinics in Tehran. Sixty people with
chronic stroke were recruited. Based on the inclusion criteria, a total of 39
stroke patients after completing the consent forms were entered to intervention
groups; splint or botulinum toxin injection or combined splint/botulinum toxin
injection. They were followed up about three months and the evaluations were done
monthly. Goniometry was the method to measure the range of motion, and Modified
Ashworth Scale was used to examine the spasticity and the upper extremity
function was scored based on Fugl- Meyer Assessment. Statistical analysis was
done using SPSS 17. And ANOVAs was used for comparison between groups and times.
Significance was set at 0.05. RESULTS: All outcome measures were improved within
each group but the differences between splint group and BTX-A group and the BTX-A
splint group was not significant in most outcomes during the 3 periods (first
evaluation until end of the first month, the end of first month until the end of
second month, the end of second month until the end of the third month) (p>0.05).
The results also showed that the changes in elbow's spasticity (p=0.05) and
wrist's spasticity (p=0.007) and upper extremity function (p=0.04) were obvious
between the three groups over the 3-months and the difference in the group of
combined use of botulinum toxin, and the splint was more than other groups.
CONCLUSION: In this study, the effects of botulinum toxin injection and Volar
Dorsal Wrist/Hand Immobilization splint and the combined use of botulinum
injection and splint were obvious in all groups but was not significantly
different between the interventions in a 3-month follow-up.
PMID- 27493919
TI - Is the status of diabetes socioeconomic inequality changing in Kurdistan
province, west of Iran? A comparison of two surveys.
AB - BACKGROUND: About 80% of deaths in 350 million cases of diabetes in the world
occur in low and middle income countries. The aim of this study was to determine
the status of diabetes socioeconomic inequality and the share of determinants of
inequalities in Kurdistan Province, West of Iran, using two surveys in 2005 and
2009. METHODS: Data were collected from non-communicable disease surveillance
surveys in Kurdistan in 2005 and 2009. In this study, the socioeconomic status
(SES) of the participants was determined based on the residential area and assets
using principal component analysis statistical method. We used concentration
index and logistic regression to determine inequality. Decomposition analysis was
used to determine the share of each determinant of inequality. RESULTS: The
prevalence of diabetes expressed by individuals changed from 0.9% (95% CI: 0.6
1.3) in 2005 to 3.1% (95% CI: 2-4) in 2009. Diabetes Concentration Index changed
from -0.163 (95% CI: -0.301- -0.024) in 2005 to 0.273 (95% CI: 0.101-0.445) in
2009. The results of decomposition analysis revealed that in 2009, 67% of the
inequality was due to low socioeconomic status and 16% to area of residence;
i.e., living in rural areas. CONCLUSION: The prevalence of diabetes significantly
increased, and the diabetes inequality shifted from the poor people to groups
with better SES. Increased prevalence of diabetes among the high SES individuals
may be due to their better responses to diabetes control and awareness programs
or due to the type of services they were provided during these years.
PMID- 27493920
TI - Diet quality in obese/overweight individuals with/without metabolic syndrome
compared to normal weight controls.
AB - BACKGROUND: Metabolic syndrome (MetS) is a serious public health concern
worldwide; however, the pathogenesis of this disease has not been yet cleared.
This study aimed to compare diet quality in obese/overweight participants
with/without metabolic syndrome with normal weight controls. METHODS: This was a
comparative study on 147 Iranian adults under treatment at the Endocrinology
Center of Tehran University of Medical Sciences. They were assigned into three
groups (normal weight, obese weight with/without MetS) according to the inclusion
exclusion criteria. Metabolic syndrome was defined according to the NCEP ATPIII
consensus criteria. Healthy Eating Index Data were obtained from the validated
FFQ to determine the diet quality index scores, using the Healthy Eating Index
2010. RESULTS: Our findings demonstrated that FBS, TG, SBP, WC and weight were
higher among MetS patients compared to the both weight matched and non-weight
matched participants, while HDL-c was lowest in this group (p<0.05). A
statistically significant difference was found between healthy weight controls
and obese/overweight participants with/without MetS in HEI-2010, and 9 of the 12
HEI-2010 components score (p<0.05). CONCLUSION: Our study revealed that low diet
quality was a risk factor in developing MetS.
PMID- 27493921
TI - The relationship between sodium intake and some bone minerals and osteoporosis
risk assessment instrument in postmenopausal women.
AB - BACKGROUND: The results of the studies on the effects of sodium on bone
metabolism have been inconsistent. There is no definitive answer to the question
of whether sodium restriction can be associated with a lower incidence of
osteoporosis. What reinforces the necessity of designing this study is the lack
of findings with the approach of examining the effects of sodium on bone in our
country. METHODS: This was a cross-sectional study conducted on 185 retired
female teachers aged 45 to 70. Sodium intake was evaluated using two methods: A
24-hour recall and a 12-hour urine sample. To assess bone health, ORAI index was
calculated for each individual. Urinary calcium, phosphorus, potassium and serum
vitamin D and PTH were measured as laboratory variables. To compare the general
characteristics of the participants across tertiles of urinary sodium, the
analysis of variance (ANOVA) was used for quantitative variables and the Chi
square test for categorical variables. RESULTS: Phosphorous, calcium and
potassium urinary excretion rate increased with the increase in urinary sodium
(p<0.05). However, the changes in serum vitamin D, and PTH levels across tertiles
of urinary sodium were not significant. Changes in urinary sodium levels were not
significant (p=0.933) in ORAI groups (sorted by rating). The relationship between
urinary calcium and sodium was apparent in low calcium intake (r=0.415, p<0.001),
but not in higher calcium intake (r=0.144, p=0.177). CONCLUSION: Although urinary
calcium and potassium increased with the increase in sodium intake, no
relationship was found between sodium and ORAI.
PMID- 27493922
TI - Does PTEN gene mutation play any role in Li-Fraumeni syndrome.
AB - BACKGROUND: Li-Fraumeni syndrome (LFS) is one of the most serious hereditary
cancer syndromes with a high risk of malignancy in childhood. This syndrome is an
autosomal dominant cancer predisposing syndrome due to a germline mutation in the
TP53 tumor suppressor gene. METHODS: In this study, a representative family case
of Li-Fraumeni syndrome is described. The proband of this family was a 43-year
old male who had osteosarcoma of the mandible and a positive family history of
cancer. His mother died at the age of 29 of brain cancer; his sister died at the
age of 18 of breast cancer; his brother died at the age of 36 of liver cancer;
and another sister of his died at the age of 16 of leukemia. Complete sequence
analysis of the TP53 and PTEN genes was performed in this family. We used
standard diagnostic tools such as sequencing and multiplex ligation-dependent
probe amplification (MLPA) to analyze these two genes in this family. The exons
and flanking exon-intron junctions of the TP53 and PTEN genes were sequenced.
RESULTS: We detected a germline mutation in the TP53 gene in this family that was
previously reported as somatic mutation in LFS in the catalogue of somatic
mutations in cancer (COSMIC). In addition, according to the International Agency
for Research of Cancer (IARC) database, a 19-year-old male patient with sarcoma
was recently reported to have this germline mutation. We also found two new IVS
variations in the PTEN gene, one of which can be a suggestive evidence of an
effect on the splicing of PTEN. CONCLUSION: Genomic modifications for tumor risk
and genotype-phenotype correlations in LFS are still to be identified. We believe
every new finding in this area can provide new insights into the pathogenesis and
progression of Li-Fraumeni syndrome.
PMID- 27493923
TI - Impact of endoscopic endonasal pituitary surgery on nasal airway patency.
AB - BACKGROUND: Nose is used as a corridor in endoscopic endonasal transsphenoidal
approach (EETSA) for pituitary adenoma. Thus, it may affect the nasal airway
patency, function and sinonasal-related quality of life. The aim of this study is
to objectively and subjectively evaluate these effects. METHODS: In this
prospective study, 43 patients with pituitary adenoma who were candidates for
EETSA from March 2012 to October 2013 were enrolled. The patients were evaluated
preoperatively using acoustic rhinometry and rhinomanometry (with/without the use
of decongestant drops) and asked to complete the 22-Item Sinonasal Outcome Test
(SNOT-22) questionnaire. The tests were repeated at one and three months
postoperatively. The preoperative data were compared with the first and second
postoperative ones using paired-sample t-test. RESULTS: Without the use of
decongestant drops, the total airway resistance increased significantly
(p=0.016), and the nasal airflow decreased significantly (p=0.031) in the first
postoperative evaluation. However, in the 3rd postoperative month, the difference
was not significant. With the use of decongestant drops, the objective parameters
showed no significant changes compared to preoperative data even at the first
evaluation. The SNOT- 22 scores also did not differ significantly in 1st and 3rd
postoperative months. The first postoperative SNOT-22 showed a strong correlation
with the second minimal cross-sectional area on simultaneous evaluation, and with
the preoperative total airway resistance. CONCLUSION: EETSA has a transient
adverse effect on the nasal patency that quickly improves, making it a safe
approach for the sinonasal system. Rhinomanometry is the most sensitive test for
detecting these nasal functional changes objectively.
PMID- 27493924
TI - The relationship between different diet quality indices and severity of airflow
obstruction among COPD patients.
AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health
problem worldwide. Smoking is the number one cause of COPD; however, genetic,
environmental and dietary factors contribute to the etiology of this disease. In
this study, we assessed the association between three diet quality indices -the
Healthy Eating Index-2005 (HEI-2005), the Healthy Eating Index-2010 (HEI-2010),
and Mediterranean Diet Score (MED)- and the severity of disease in COPD patients.
METHODS: This cross-sectional study was performed at Rasul-e-Akram Hospital in
Tehran on 121 COPD patients with the mean age of (SD) of 66.1(10.9) years. A
pulmonary specialist diagnosed all participants based on a spirometry test. They
were categorized into four groups (1, 2, 3, 4 stages of disease). Three diet
quality indices, spirometry test and determination of disease severity were
performed for all the participants. ANCOVA and Kruskal-Wallis test were used to
assess the relationship between dietary quality indices and severity of the
disease. The relationship between HEI-2010, HEI-2005, MED score, their components
and lung function was assessed using a multiple linear regression analysis. All
analyses were done using SPSS 18. RESULTS: Reduction of the Healthy Eating Index
2010 and MED score were observed along with the increase in disease severity, but
they were not significant. The relationship between the three diet quality
indices and lung function showed a significant association between MED score and
Forced expiratory volume in one second (FEV1), The Forced Vital Capacity (FVC)
(beta=2.9, 95% CI (1.1, 4.8), p=0.002), (beta=2.8, 95% CI (0.9, 4.8), p=0.007),
respectively. CONCLUSION: Mediterranean dietary pattern and obtaining a better
score on HEI-2010 diet were associated with a better lung function test.
PMID- 27493925
TI - The effect of green tea extract supplementation on sputum smear conversion and
weight changes in pulmonary TB patients: A randomized controlled trial.
AB - BACKGROUND: Acceleration in sputum smear conversion helps faster improvement and
decreased probability of the transfer of TB. In this study, we aimed to
investigate the effect of green tea extract supplementation on sputum smear
conversion and weight changes in smear positive pulmonary TB patients in Iran.
METHODS: In this double blind clinical study, TB patients were divided into
intervention, (n=43) receiving 500 mg green tea extract (GTE), and control groups
(n=40) receiving placebo for two months, using balanced randomization. Random
allocation and allocation concealment were observed. Height and weight were
measured at the beginning, and two and six months post-treatment. Evaluations
were performed on three slides, using the ZiehlNeelsen method. Independent and
paired t test, McNemar's, Wilcoxon, Kaplan-Meier, Cox regression model and Log
Rank test were utilized. Statistical significance was set at p<0.05. This trial
was registered under IRCT201212232602N11. RESULTS: The interventional changes and
the interactive effect of intervention on weight were not significant (p>0.05).
In terms of shortening the duration of conversion, the case to control proportion
showed a significant difference (p=0.032). Based on the Cox regression model, the
hazard ratio of the relative risk of delay in sputum smear conversion was 3.7
(p=0.002) in the higher microbial load group compared to the placebo group and
0.54 (95% CI: 0.31-0.94) in the intervention compared to the placebo group.
CONCLUSION: GTE decreases the risk of delay in sputum smear conversion, but has
no effect on weight gain. Moreover, it may be used as an adjuvant therapy for
faster rehabilitation for pulmonary TB patients.
PMID- 27493926
TI - Incidence trends of colorectal cancer in Iran during 2000-2009: A population
based study.
AB - BACKGROUND: As the third leading cause of death, cancers have a special place in
the Iranian health system. Several studies have been done in some regions of the
country with few years of follow-ups, but this was the first standardized study
to investigate the incidence trends of colorectal cancer in Iran in a one-decade
period. METHODS: The registered data for colorectal cancer cases in National
Cancer Registry System were extracted from the Center for Disease Control &
Management of Ministry of Health. The codes from 18 to 21 among cancers were
selected for colon and rectum cancers. Incidence rates were directly
standardized, using WHO population. The significance of incidence rate trends was
tested through Poisson regression. RESULTS: In this study, 36,650 cases of
colorectal cancer were observed for 10 years in Iran, which increased from 813
cases in 2000 to 6,210 cases in 2009. Gender ratio of men to women was 1.39.
Significant increasing trends of colorectal cancer were observed during the
period of the study. The standardized incidence rate increased from 1.6 per
100,000 persons per year in 2000 to 11.3 in 2009 in males (p<0.001), and it
increased from 1.6 per 100,000 persons per year in 2000 to 10.9 in 2009 in
females (p<0.001). CONCLUSION: Colorectal cancer has an increasing trend in Iran.
The rising trend of colorectal cancer as well as other types of cancers is
partially due to improvement in cancer registry systems in the early years of
registry. Moreover, westernized lifestyle and an increase in environmental risks
could explain this rising trend.
PMID- 27493927
TI - Economic inequalities in dental care utilizations in Iran: Evidence from an urban
region.
AB - BACKGROUND: Health utilization inequality is a major concern for health
policymakers. Equality in utilization of services is very important for having a
healthy society. The aim of this study was to describe inequality in dental care
utilization in Iran, Therefore, concentration index, its curve, and the
predictors of inequality in utilization of dental services and their spending
were calculated. METHODS: Data of a health utilization survey which previously
had been gathered in Shiraz, Iran were used for this study. Tobit and Poisson
estimators were used to estimate utilization and out of pocket models.
Furthermore, concentration index and curve was calculated to show inequality in
dental care utilization. RESULTS: High inequalities was found in dental care
utilization in Iran (concentration index=0.19). In the utilization model, the
relationship between income and utilization was positive. People with higher
income could utilize more services. Being covered by insurance increased the
probability of dental care utilizations too. CONCLUSION: Policy makers must find
solutions like increase the coverage of dental insurances to decrease inequality
in dental care utilization.
PMID- 27493928
TI - Health technology assessment on super oxidized water for treatment of chronic
wounds.
AB - BACKGROUND: Super oxidized water (SOW), as a novel antiseptic solution, is used
with claims of effectiveness and cost effectiveness in healing chronic wounds
such as diabetic foot, infectious postoperative ulcers and burn ulcers. We
conducted a health technology assessment to evaluate the clinical evidence from
clinical and randomized trials for this disinfection. This study aims to evaluate
the safety, effectiveness and cost-effectiveness of this technology in Iran, for
using as a wound disinfectant. METHODS: Systematic literature searches were
conducted from October 2013 to March 2014 for the following medical databases:
OVID MEDLINE, CINAHL, the Cochrane Library and the PICO terms were included and
then analyzed by Cochrane assessment criteria. RESULTS: Out of 705 articles,
twelve potentially relevant trials were identified. Others that didn't come with
the PICO criteria were excluded. 5 randomized controlled trials, 5 clinical
trials, a rapid HTA and a case series that had studied the effectiveness of super
oxidized water on patients with different chronic wounds, were included. Most of
these trials were assessing similar sets of outcomes as the Safety and Effect on
Healing days to re-epithelization, healing rate, effect on Infection bacterial
counts and infection rates. CONCLUSION: Super oxidized water is a safe, effective
and cost effective irrigation and cleansing agent due to the performed analysis
in comparison with current treatment as povidone iodine for treating wound
infections.
PMID- 27493929
TI - Religious experiences of Iranian transgenders: A qualitative study.
AB - BACKGROUND: Gender identity disorder and its treatment with sex reassignment
surgery is a profound experience, which can affect the mental, interpersonal,
social and religious aspects of one's life. METHODS: This was a qualitative
content analysis study focusing on the various dimensions of the experiences of
seven patients suffering from gender identity disorder in a female-to-male
subgroup. This study presents a report concerning the religious aspects of their
experience. RESULTS: The findings of this study were categorized into the four
following conceptual categories: sense of guilt; accomplishing a sense of
submission to God's will as well as God's pleasing; practical commitment to
religion; and rejection by the religious communities. CONCLUSION: Diminishing
religion to spirituality comprised the core experiences of these patients having
intimate relations with such concepts as secularism, stigma, and technocracy.
PMID- 27493930
TI - The efficacy of a home-mechanical traction unit for patients with mild to
moderate cervical osteoarthrosis: A pilot study.
AB - BACKGROUND: Traction has been suggested to be an effective treatment for symptoms
of neck disorder in patients with no contraindications. However, according to
previous researches, the effectiveness of traction is controversial, particularly
compared to other conservative treatments. This trial was conducted to evaluate
the effect of sustained traction, using an over-the-door home cervical traction
unit in combination with routine physical therapy on reducing cervical
osteoarthrosis symptoms including neck pain, medication use and disability level
compared to routine physical therapy alone. METHODS: In this double- blinded
pilot study with a pre-post test design and a control group, 20 women with mild
to moderate osteoarthrosis were systematically assigned to the over-the-door home
cervical traction (mean+/-SD age: 50.5+/-4.45yrs) or control groups (mean+/-SD
age: 55.6+/-7.34yrs). Pain, level of disability, and drug consumption were
evaluated before and after 10 sessions of intervention. Data were analyzed using
parametric or non-parametric statistic including the paired-sample t-test,
independent sample t-test, and Wilcoxon and Mann-Whitney u test for intra and
inter groups comparison based on the Kolmogorov-Smirnov test results. RESULTS:
Patients in both groups showed a significant decrease in pain intensity and
disability level (p<0.05). Despite the greater improvement in pain levels and
disability in the experimental group compared to the controls, the differences
were not significant (p>0.05). No significant differences were found in terms of
drugs consumption within and between the groups at the end of the treatment
(p>0.05). CONCLUSION: The results revealed that applying sustained traction using
an over-the-door home cervical traction unit was not significantly superior to
the routine physical therapy and ergonomic training to manage symptoms including
neck pain and disability in a small group of mild to moderate cervical
osteoarthrosis patients.
PMID- 27493931
TI - Health system responsiveness after health sector evolution plan (HSEP): An
inpatient survey in Kermanshah in 2015.
AB - BACKGROUND: Responsiveness is one of the three main goals of the health system
introduced by World Health Organization. This study aimed at examining health
system responsiveness after Health Sector Evolution Plan in Kermanshah, Western
Iran. METHODS: A sample of 335 hospitalized patients was selected using
proportionate allocation to population size method in the city of Kermanshah
(Iran) in 2015. World Health Survey (WHS) questionnaire was used to collect data.
Data were analyzed using descriptive statistics and principal component analysis
by STATA 12. RESULTS: The overall health system responsiveness score was 72.6.
The best and worst performance for domains of dignity and autonomy were 82.2 and
62.5, respectively. Socio-demographic variables of the patients had no
significant effect on the total health system responsiveness score. The principal
component analysis findings indicated that 68% of the variance of the overall
responsiveness score was explained by four components. CONCLUSION: The overall
responsiveness score of each of the domains was higher than that of other similar
previous studies in Iran. Although it is difficult to reach a conclusion, our
findings may show better responsiveness of the health system compared to the
previous reports.
PMID- 27493932
TI - Quality of life in epileptic patients compared with healthy people.
AB - BACKGROUND: Epilepsy is a common chronic neurological disorder that has a great
impact on people's lives. Patients with epilepsy are at increased risk for poor
Quality of Life (QoL). The objective of this study was to evaluate the QoL of
epileptic patients in comparison to healthy persons. METHODS: This cross
sectional study was conducted on 52 epileptic patients from Golbu region in
Neyshabur (a city in northeast of Iran). Using Short Form Health Survey (SF-36)
scale, the data were collected between April and Jun 2012. Every patient were
compared with two healthy persons. Epileptic and healthy persons were similar for
age, sex and local residence. Pearson's correlation coefficient and t-independent
test applied for data analysis through SPSS v. 16 software. RESULTS: Of 52
epileptic patients, 24 were female (46.2%) and 28 were male (53.8%). The mean+/
SD age of epileptic patients was 40.92+/-20.33yr (Rang: 15-86yr). The total mean
score of SF- 36 in patient group was 55.88 and in healthy group 68.52and this
difference was statistically significant (p<0.001). Among the different subscales
of SF-36 in epileptic patients, the highest and the lowest mean scores were found
for social functioning and general health subscales, respectively. The mean
scores in patient group in comparison to healthy group were lower in all
subscales of SF-36 and these differences were statistically significant in all
domains (except role limitations due to physical problems domain and role
limitations due to emotional problems domain). CONCLUSION: The study showed that
epilepsy disease has an important role in QoL of patients, thus some
interventional programs are necessary to improve their QOL.
PMID- 27493933
TI - How valid is the tallquist method in screening pregnant women with anemia in poor
rural settings of southwestern Nigeria?
AB - BACKGROUND: Diagnosis of anemia is challenging in resource-poor settings due to
inadequate laboratory resources. This study assessed the validity of the
Tallquist haemoglobinometer in assessing anemia among pregnant women in Osogbo,
Southwestern Nigeria. METHODS: This was a cross - sectional study, in which 200
pregnant women of reproductive age were selected using multistage sapling method.
A checklist was used to collect socio-demographic data and the results of the
screening test. Blood collection and analysis were carried out using standardized
referenced methods. RESULTS: Mean+/-SD age of the respondents was 28.9+3.9 yrs.;
and 62 (62.6%) had up to primary level education. When Tallquist and Haematocrit
methods were compared, there was 68.4%, 83.5% and 100% likelihood of Tallquist
method (TM) diagnosing severe, moderate and mild anemia, respectively. The
validity indices of the TM versus Haematocrit method as the gold standard
revealed the sensitivity of 97.9%, specificity of 92.1%, positive predictive
value of 92.4%, and negative predictive value of 97.9% and diagnostic accuracy of
95.0%. When compared to the Haemoglobin Cyanide method, the Tallquist method
showed a calculated sensitivity of 96.6%, specificity of 87.4%, positive
predictive value of 86.0%, and negative predictive value of 97.0% and diagnostic
accuracy of 91.5%. CONCLUSION: The TM is a valid tool in screening anemia among
pregnant women in resource- poor settings and rural primary health care centers
in Southwestern Nigeria; therefore, its use should be encouraged, particularly to
assess mild to moderate anemia.
PMID- 27493934
TI - Cost-effectiveness analysis of dialysis and kidney transplant in patients with
renal impairment using disability adjusted life years in Iran.
AB - BACKGROUND: This cross-sectional study was conducted to compare the cost
effectiveness of three therapeutic methods of long-term hemodialysis, kidney
transplant from a living person and kidney transplant from a cadaver utilizing
Disability Adjusted Life Years (DALY) using data from the records of patients
referred to Afzalipour Hospital of Kerman in 2012. METHODS: This cross-sectional
study utilizing Disability Adjusted Life Years (DALY) as outcome measure, used
data from the records of patients referred to Afzalipour Hospital of Kerman in
2012. The decision tree model and decision tree software (Tree Age pro 11) were
used for data analysis. In this research, costs and effects were studied from the
patients and healthcare providers' perspective. RESULTS: In the patient's
perspective, the CER of dialysis was 5.04 times greater than transplant from a
living person and 6.15 times higher than transplant from a cadaveric donor. In
the hospital's perspective, the average cost-effectiveness ratio of dialysis was
8.4 times greater than transplant from a living person and 14.07 times higher
than transplant from a cadaver. The smaller the C-E ratio, the greater was the
cost-effectiveness. In both perspectives, the order of effectiveness of treatment
methods were transplant from a cadaver, transplant from a living person and
dialysis. CONCLUSION: Considering the results obtained in this study, measures
should be taken to increase the desire for organ donation from brain-dead
patients, living people and patients' relatives.
PMID- 27493936
TI - Comparative Brain and Central Nervous System Tumor Incidence and Survival between
the United States and Taiwan Based on Population-Based Registry.
AB - PURPOSE: Reasons for worldwide variability in the burden of primary malignant
brain and central nervous system (CNS) tumors remain unclear. This study compares
the incidence and survival of malignant brain and CNS tumors by selected
histologic types between the United States (US) and Taiwan. METHODS: Data from
2002 to 2010 were selected from two population-based cancer registries for
primary malignant brain and CNS tumors: the Central Brain Tumor Registry of the
United States and the Taiwan Cancer Registry. Two registries had similar process
of collecting patients with malignant brain tumor, and the quality of two
registries was comparative. The age-adjusted incidence rate (IR), IR ratio, and
survival by histological types, age, and gender were used to study regional
differences. RESULTS: The overall age-adjusted IRs were 5.91 per 100,000 in the
US and 2.68 per 100,000 in Taiwan. The most common histologic type for both
countries was glioblastoma (GBM) with a 12.9% higher proportion in the US than in
Taiwan. GBM had the lowest survival rate of any histology in both countries (US 1
year survival rate = 37.5%; Taiwan 1-year survival rate = 50.3%). The second
largest group was astrocytoma, excluding GBM and anaplastic astrocytoma, with the
distribution being slightly higher in Taiwan than in the US. CONCLUSION: Our
findings revealed differences by histological type and grade of primary malignant
brain and CNS tumors between two sites.
PMID- 27493935
TI - The Gap Between Clinical Research and Standard of Care: A Review of Frailty
Assessment Scales in Perioperative Surgical Settings.
AB - The elderly population in the United States is increasing exponentially in tandem
with risk for frailty. Frailty is described by a clinically significant state
where a patient is at risk for developing complications requiring increased
assistance in daily activities. Frailty syndrome studied in geriatric patients is
responsible for an increased risk for falls, and increased mortality. In efforts
to prepare for and to intervene in perioperative complications and general
frailty, a universal scale to measure frailty is necessary. Many methods for
determining frailty have been developed, yet there remains a need to define
clinical frailty and, therefore, the most effective way to measure it. This
article reviews six popular scales for measuring frailty and evaluates their
clinical effectiveness demonstrated in previous studies. By identifying the most
time-efficient, criteria comprehensive, and clinically effective scale, a
universal scale can be implemented into standard of care and reduce complications
from frailty in both non-surgical and surgical settings, especially applied to
the perioperative surgical home model. We suggest further evaluation of the
Edmonton Frailty Scale for inclusion in patient care.
PMID- 27493937
TI - Nutrient Value of Leaf vs. Seed.
AB - Major differences stand out between edible leaves and seeds in protein quality,
vitamin, and mineral concentrations and omega 6/omega 3 fatty acid ratios. Data
for seeds (wheat, rice, corn, soy, lentil, chick pea) are compared with
corresponding data for edible green leaves (kale, spinach, broccoli, duckweed).
An x/y representation of data for lysine and methionine content highlights the
group differences between grains, pulses, leafy vegetables, and animal foods.
Leaves come out with flying colors in all these comparisons. The perspective ends
with a discussion on "So why do we eat mainly seeds?"
PMID- 27493938
TI - Clinical Characteristics, Diagnostic Evaluation, and Antibiotic Prescribing
Patterns for Skin Infections in Nursing Homes.
AB - BACKGROUND: The epidemiology and management of skin infections in nursing homes
has not been adequately described. We reviewed the characteristics, diagnosis,
and treatment of skin infections among residents of nursing homes to identify
opportunities to improve antibiotic use. METHODS: This was a retrospective study
involving 12 nursing homes in the Denver metropolitan area. For residents at
participating nursing homes diagnosed with a skin infection between July 1, 2013
and June 30, 2014, clinical and demographic information was collected through
manual chart review. RESULTS: Of 100 cases included in the study, the most common
infections were non-purulent cellulitis (n = 55), wound infection (n = 27),
infected ulcer (n = 8), and cutaneous abscess (n = 7). In 26 cases, previously
published minimum clinical criteria for initiating antibiotics (Loeb criteria)
were not met. Most antibiotics (n = 52) were initiated as a telephone order
following a call from a nurse, and 41 patients were not evaluated by a provider
within 48 h after initiation of antibiotics. Nearly all patients (n = 95) were
treated with oral antibiotics alone. The median treatment duration was 7 days
(interquartile range 7-10); 43 patients received treatment courses of >=10 days.
CONCLUSION: Most newly diagnosed skin infections in nursing homes were non
purulent infections treated with oral antibiotics. Antibiotics were initiated by
telephone in over half of cases, and lack of a clinical evaluation within 48 h
after starting antibiotics was common. Improved diagnosis through more timely
clinical evaluations and decreasing length of therapy are important opportunities
for antibiotic stewardship in nursing homes.
PMID- 27493939
TI - The Effects of Dietary Fat and Iron Interaction on Brain Regional Iron Contents
and Stereotypical Behaviors in Male C57BL/6J Mice.
AB - Adequate brain iron levels are essential for enzyme activities, myelination, and
neurotransmitter synthesis in the brain. Although systemic iron deficiency has
been found in genetically or dietary-induced obese subjects, the effects of
obesity-associated iron dysregulation in brain regions have not been examined.
The objective of this study was to examine the effect of dietary fat and iron
interaction on brain regional iron contents and regional-associated behavior
patterns in a mouse model. Thirty C57BL/6J male weanling mice were randomly
assigned to six dietary treatment groups (n = 5) with varying fat (control/high)
and iron (control/high/low) contents. The stereotypical behaviors were measured
during the 24th week. Blood, liver, and brain tissues were collected at the end
of the 24th week. Brains were dissected into the hippocampus, midbrain, striatum,
and thalamus regions. Iron contents and ferritin heavy chain (FtH) protein and
mRNA expressions in these regions were measured. Correlations between
stereotypical behaviors and brain regional iron contents were analyzed at the 5%
significance level. Results showed that high-fat diet altered the stereotypical
behaviors such as inactivity and total distance traveled (P < 0.05). The high-fat
diet altered brain iron contents and FtH protein and mRNA expressions in a
regional-specific manner: (1) high-fat diet significantly decreased the brain
iron content in the striatum (P < 0.05), but not other regions, and (2) thalamus
has a more distinct change in FtH mRNA expression compared with other regions.
Furthermore, high-fat diet resulted in a significant decreased total distance
traveled and a significant correlation between iron content and sleeping in
midbrain (P < 0.05). Dietary iron also decreased brain iron content and FtH
protein expression in a regionally specific manner. The effect of interaction
between dietary fat and iron was observed in brain iron content and behaviors.
All these findings will lay foundations to further explore the links among
obesity, behaviors, and brain iron alteration.
PMID- 27493941
TI - Standards and Challenges of Care for Colorectal Cancer Today.
PMID- 27493942
TI - Diagnostics and Epidemiology of Colorectal Cancer.
AB - Colorectal cancer is one of the leading causes of cancer-related morbidity and
mortality. Main risk factors include advanced age, family history, male sex, and
lifestyle factors. Screening can reduce incidence and death from colorectal
cancer. Therefore, prevention and early detection are crucial in order to detect
and remove pre-neoplastic adenomas and to detect cancers at early stages.
Colonoscopy, flexible sigmoidoscopy, and fecal occult blood tests are established
tools for screening. Newer fecal immunochemical tests reveal higher sensitivities
for advanced adenoma and cancer than guaiac-based hemoccult tests. Molecular
stool and blood tests as well as virtual colonoscopy and colon capsule endoscopy
are promising new developments so far not established as routine instruments for
the prevention and early detection of colorectal cancer. Colonoscopy is the
method of choice for the diagnosis of colorectal cancer and for adenoma removal.
Prognosis is essentially dependent on the tumor stage at the time of the initial
diagnosis. Proper staging based on imaging prior to therapy is a prerequisite. In
rectal cancer, local staging is an essential requirement for the identification
of appropriate candidates for neoadjuvant therapy.
PMID- 27493940
TI - A Review of the Giant Protein Titin in Clinical Molecular Diagnostics of
Cardiomyopathies.
AB - Titin (TTN) is known as the largest sarcomeric protein that resides within the
heart muscle. Due to alternative splicing of TTN, the heart expresses two major
isoforms (N2B and N2BA) that incorporate four distinct regions termed the Z-line,
I-band, A-band, and M-line. Next-generation sequencing allows a large number of
genes to be sequenced simultaneously and provides the opportunity to easily
analyze giant genes such as TTN. Mutations in the TTN gene can cause
cardiomyopathies, in particular dilated cardiomyopathy (DCM). DCM is the most
common form of cardiomyopathy, and it is characterized by systolic dysfunction
and dilation of the left ventricle. TTN truncating variants have been described
as the most common cause of DCM, while the real impact of TTN missense variants
in the pathogenesis of DCM is still unclear. In a recent population screening
study, rare missense variants potentially pathogenic based on bioinformatic
filtering represented only 12.6% of the several hundred rare TTN missense
variants found, suggesting that missense variants are very common in TTN and are
frequently benign. The aim of this review is to understand the clinical role of
TTN mutations in DCM and in other cardiomyopathies. Whereas TTN truncations are
common in DCM, there is evidence that TTN truncations are rare in the
hypertrophic cardiomyopathy (HCM) phenotype. Furthermore, TTN mutations can also
cause arrhythmogenic right ventricular cardiomyopathy (ARVC) with distinct
clinical features and outcomes. Finally, the identification of a rare TTN
missense variant cosegregating with the restrictive cardiomyopathy (RCM)
phenotype suggests that TTN is a novel disease-causing gene in this disease.
Clinical diagnostic testing is currently able to analyze over 100 cardiomyopathy
genes, including TTN; however, the size and presence of extensive genetic
variation in TTN presents clinical challenges in determining significant disease
causing mutations. This review discusses the current knowledge of TTN genetic
variations in cardiomyopathies and the impact of the diagnosis of TTN pathogenic
mutations in the clinical setting.
PMID- 27493943
TI - Imaging Procedures for Colorectal Cancer.
AB - BACKGROUND: Radiological imaging plays an important role in the setting of
staging, follow-up, and imaging-guided treatment of colorectal carcinoma (CRC).
METHODS: This review aims to summarize the current state of the art of the
different radiological imaging procedures in CRC including an overview over
recently published national and European guidelines and consensus statements
concerning the imaging of CRC patients. RESULTS AND CONCLUSION: Radiological
imaging is widely embedded in national and international guidelines, and
structured reporting is recommended.
PMID- 27493944
TI - Radiotherapy for Colorectal Cancer: Current Standards and Future Perspectives.
AB - BACKGROUND: Multimodal treatment approaches are indispensable for patients with
advanced-stage colorectal cancer. Radiotherapy has been established as essential
part of perioperative concepts and was introduced as an option to face challenges
such as local relapse or oligometastases. METHODS: A literature review was
performed to summarize evidence and current standards of radiotherapeutic
concepts in the treatment of colorectal cancer. RESULTS: For stage II/III rectal
cancer, neoadjuvant radiotherapy is superior to adjuvant treatment. Two
preoperative regimens have been established and are commonly used with different
objectives: short-course radiotherapy (SC-RT) and long-course chemoradiotherapy
(LC-CRT). Both reduce the risk of local relapse. Additionally, LC-CRT aims at
downsizing the tumor to potentially reduce radicalness of surgery. There is
increasing evidence that not all stage II/III rectal cancer patients need
neoadjuvant irradiation but also that in some cases surgery might be omitted.
Stereotactic body radiotherapy (SBRT) of the liver shows high rates of local
control in oligometastatic patients. Intraoperative and particle radiotherapy
extend the spectrum of treatment options for locally recurrent patients.
CONCLUSION: Radiotherapeutic concepts are crucial for the primary management of
locally advanced colorectal cancer and can essentially contribute to treatment
approaches in locally recurrent, oligometastatic or palliative patients.
PMID- 27493945
TI - Treatment of Metastatic Colorectal Cancer: Standard of Care and Future
Perspectives.
AB - Palliative chemotherapy for metastatic colorectal cancer has undergone
substantial changes in recent years. The implementation of modern biologicals in
the treatment has substantially improved overall survival up to 30 months. With
the increasing number of therapeutic options, the question of optimal treatment
sequence arises, which is addressed in current studies like FIRE 4 or STRATEGIC
1. Furthermore, clinical and molecular biomarkers to predict efficacy and
tolerability are urgently needed. Today, the detection of activating RAS
mutations is the only validated biomarker which precludes patients from anti-EGFR
treatment. The detection of BRAF mutation V600E is associated with a very poor
prognosis corresponding to a survival of 9-12 months. Prospective trials
evaluating an optimal approach to this subgroup are still missing. First results
from strategies targeting the aberrant signal transduction are promising and
require further validation. Despite the advances so far, life expectancy
unfortunately continues to be limited in the majority of patients with metastatic
colorectal cancer. New strategies are needed to improve the prognosis. To this
end, the identification of Her2/neu as a potential target and first experiences
with checkpoint inhibition in patients with mismatch repair-deficient tumors are
promising and also require further validation.
PMID- 27493946
TI - Surgery for Colorectal Cancer - Trends, Developments, and Future Perspectives.
AB - BACKGROUND: Although colorectal surgery is long established as the mainstay
treatment for colon cancer, certain topics regarding technical fine-tuning to
increase postsurgical recurrence-free survival have remained a matter of debate
throughout the past years. These include complete mesocolic excision (CME),
treatment strategies for metastatic disease, significance of hyperthermic
intraperitoneal chemotherapy (HIPEC), and surgical techniques for the treatment
of colorectal cancer recurrence. In addition, new surgical techniques have been
introduced in oncologic colorectal surgery, and their potential to provide
sufficiently radical resection has yet to be proven. METHODS: A structured review
of the literature was performed to identify the current state of the art with
regard to the mentioned key issues in colorectal surgery. RESULTS: This article
provides a comprehensive review of the current literature addressing the above
mentioned current challenges in colorectal surgery. The focus lies on the impact
of CME and, in relation to this, on lymph node dissection, as well as on
treatment of metastatic disease including peritoneal spread, and finally on the
treatment of recurrent disease. CONCLUSION: Uniformly, the current literature
reveals that surgery aiming at complete malignancy elimination within multimodal
treatment approaches represents the fundamental quantum leap for the achievement
of long-term tumor-free survival.
PMID- 27493947
TI - Minimally Invasive Surgery for the Treatment of Colorectal Cancer.
AB - BACKGROUND: Reduction in operative trauma along with an improvement in endoscopic
access has undoubtedly occupied surgical minds for at least the past 3 decades.
It is not at all surprising that minimally invasive colon surgery has come a long
way since the first laparoscopic appendectomy by Semm in 1981. It is common
knowledge that the recent developments in video and robotic technologies have
significantly furthered advancements in laparoscopic and minimally invasive
surgery. This has led to the overall acceptance of the treatment of benign
colorectal pathology via the endoscopic route. Malignant disease, however, is
still primarily treated by conventional approaches. METHODS AND RESULTS: This
review article is based on a literature search pertaining to advances in
minimally invasive colorectal surgery for the treatment of malignant pathology,
as well as on personal experience in the field over the same period of time. Our
search was limited to level I and II clinical papers only, according to the
evidence-based medicine guidelines. We attempted to present our unbiased view on
the subject relying only on the evidence available. CONCLUSION: Focusing on
advances in colorectal minimally invasive surgery, it has to be stated that there
are still a number of unanswered questions regarding the surgical management of
malignant diseases with this approach. These questions do not only relate to the
area of boundaries set for the use of minimally invasive techniques in this field
but also to the exact modality best suited to the treatment of every particular
case whilst maintaining state-of-the-art oncological principles.
PMID- 27493949
TI - Effects of Platelet-Derived Endothelial Cell Growth Factor and Doppler Perfusion
Index in Patients with Colorectal Hepatic Metastases.
AB - BACKGROUND: We aimed to find out if there is a correlation between Doppler
perfusion index (DPI) and platelet- derived endothelial cell growth factor (PD
ECGF), which is an angiogenic factor with angiopoietic function, in patients with
colorectal carcinoma. METHODS: 50 colorectal carcinoma patients (22 cases with
liver metastases, 28 cases without liver metastases) and 50 healthy controls were
assessed with Doppler ultrasound as a preoperative evaluation. PD-ECGF expression
in postoperative specimens of the 50 cases with colorectal carcinoma was assayed
by immunohistochemistry and real-time polymerase chain reaction methods. RESULTS:
The mean DPI value was 0.29 +/- 0.05 in patients suffering from colon cancer with
hepatic metastases and 0.12 +/- 0.03 in the healthy control group. The DPI value
was significantly higher in patients with liver metastases (p < 0.05). PD-ECGF
expression in patients with colorectal liver metastases was significantly higher
than that in the group without liver metastases (p < 0.05). A positive
correlation was found between DPI value and PD-ECGF expression in patients with
liver metastases (p < 0.05). CONCLUSIONS: DPI and PD-ECGF may be valuable factors
when screening hepatic metastases in patients with colorectal cancer and serve as
practical measurements in postoperative follow-up.
PMID- 27493948
TI - Physical Activity and Nutrition in Primary and Tertiary Prevention of Colorectal
Cancer.
AB - BACKGROUND: Lifestyle factors play a pivotal role in the primary and tertiary
prevention of colorectal cancer. The purpose of this review article is to
summarize data concerning the effect of the lifestyle factors physical activity
(PA) and nutrition in primary and, more importantly, tertiary prevention of
colorectal cancer (CRC). METHODS: Focusing on the influence of lifestyle factors
on prognosis und quality of life (QOL), a comprehensive literature search of
clinical studies published mainly in the years 2000 until 2015 was performed and
the current knowledge based on these clinical studies reviewed. RESULTS: Besides
avoiding risk factors (such as smoking and overindulgence in alcohol), healthy
weight, regular and moderate PA as well as a diet which contains fruit,
vegetables, poultry, and fish (so-called 'Mediterranean' diet) may reduce the
risk of the disease significantly. Patients already diagnosed with CRC can also
actively improve the prognosis of CRC and QOL by changing their lifestyle.
Patients commencing moderate exercise and modifying their eating habits in terms
of a 'Mediterranean' diet can reduce cancer-specific and overall mortality by up
to 40% and significantly increase their quality of life already during
chemotherapy. Therefore, moderate physical exercise, calorie restriction, and a
Mediterranean dietary pattern for patients with CRC should be recommended by
physicians treating these patients. In fact, the World Cancer Research
Fund/American Institute for Cancer Research (AICR/WCRF) systematic literature
review from 2007 shows that the lifestyle changes recommended after diagnosis are
the same for primary prevention of this disease. CONCLUSION: Lifestyle changes
such as moderate PA and a Mediterranean diet significantly improve the QOL as
well as the prognosis of patients suffering from colorectal disease. However, the
effect of lifestyle changes is mostly based on observational studies, while only
few studies are prospective and none are randomized. Therefore, these
observational studies warrant controlled randomized trials to prove the
effectiveness of lifestyle interventions on QOL and cancer recurrence.
PMID- 27493950
TI - Intussusception of the Appendix and Ileum Endometriosis: A Case Report.
AB - BACKGROUND: Intussusception of the appendix is a very rare condition. It may
clinically mimic acute or chronic abdominal diseases or can be asymptomatic. CASE
REPORT: This paper describes our experience with intussusception of the appendix.
We report a case of a female with appendiceal intussusception and ileum
endometriosis. CONCLUSION: It is important to know about such a rare condition in
order to avoid mistaking it with other abdominal diseases. However, diagnosis is
rarely made preoperatively.
PMID- 27493951
TI - mHealth self-care interventions: managing symptoms following breast cancer
treatment.
AB - BACKGROUND: Many women suffer from daily distressing symptoms related to
lymphedema following breast cancer treatment. Lymphedema, an abnormal
accumulation of lymph fluid in the ipsilateral body area or upper limb, remains
an ongoing major health problem affecting more than 40% of 3.1 million breast
cancer survivors in the United States. Patient-centered care related to
lymphedema symptom management is often inadequately addressed in clinical
research and practice. mHealth plays a significant role in improving self-care,
patient-clinician communication, and access to health information. The-Optimal
Lymph-Flow health IT system (TOLF) is a patient-centered, web-and-mobile-based
educational and behavioral mHealth interventions focusing on safe, innovative,
and pragmatic electronic assessment and self-care strategies for lymphedema
symptom management. The purpose of this paper is to describe the development and
test of TOLF system. METHODS: The development of TOLF was guided by the Model of
Self-Care for Lymphedema Symptom Management and designed based on principles
fostering accessibility, convenience, and efficiency of mHealth system to enhance
training and motivating assessment of and self-care for lymphedema symptoms. Test
of TOLF was accomplished by conducting a psychometric study to evaluate
reliability, validity, and efficiency of the electronic version of Breast Cancer
and Lymphedema Symptom Experience Index (BCLE-SEI), a usability testing and a
pilot feasibility testing of mHealth self-care interventions. RESULTS: Findings
from the psychometric study with 355 breast cancer survivors demonstrated high
internal consistency of the electronic version of the instrument: a Cronbach's
alpha coefficient of 0.959 for the total scale, 0.919 for symptom occurrence, and
0.946 for symptom distress. Discriminant validity of the instrument was supported
by a significant difference in symptom occurrence (z=-6.938, P<0.000), symptom
distress (z=-5.894, P<0.000), and total scale (z=-6.547, P<0.000) between breast
cancer survivors with lymphedema and those without it. Findings of usability
testing showed that breast cancer survivors were very satisfied with the mHealth
self-care interventions: 90% rated the system having no usability problems; 10%
noted minor cosmetic problems: spelling errors or text font size. The majority of
participants 96.6% strongly agreed that the system was easy to use and effective
in helping to learn about lymphedema, symptoms and self-care strategies.
Feasibility testing demonstrated that a 12-week one group intervention using TOLF
had significantly positive effects on less pain (P=0.031), less soreness
(P=0.021), less aching (P=0.024), less tenderness (P=0.039), fewer numbers of
lymphedema symptoms (P=0.003), and improved symptom distress (P=0.000) at 12
weeks after intervention. Themes from the qualitative data included empowerment,
high quality information, loving avatar simulation videos, easy accessibility,
and user-friendliness. CONCLUSIONS: TOLF system using the electronic version of
the instrument is able to assess patients' lymphedema symptoms with high
reliability and validity. TOLF system is also able to deliver self-care
interventions to enhance self-care strategies for lymphedema symptom management.
PMID- 27493952
TI - Influence of the Dermis Thickness on the Results of the Skin Treatment with
Monopolar and Bipolar Radiofrequency Currents.
AB - Electrically layered tissue structure significantly modifies distribution of
radiofrequency (RF) current in the dermis and in the subcutaneous adipose tissue
comparing to that in a homogeneous medium. On the basis of the simple model of RF
current distribution in a two-layer skin containing dermis and subcutis, we
assess the influence of the dermal thickness on the current density in different
skin layers. Under other equal conditions, current density in the dermis is
higher for the skin having thinner dermis. This contradicts the main paradigm of
the RF theory stating that treatment results are mainly dependent on the maximal
temperature reached in a target tissue, since the best short- and long-term
clinical results of RF application to the skin were reported in the areas having
thicker dermis. To resolve this contradiction, it is proposed that the long-term
effect of RF can be realized through a structural modification of the
subcutaneous fat depot adjacent to the treated skin area. Stimulation of these
cells located near the interface dermis/subcutis will demand the concentration of
applied RF energy in this area and will require the optimal arrangement of RF
electrodes on the skin surface.
PMID- 27493953
TI - A Tobacco-Derived Thymosin beta4 Concatemer Promotes Cell Proliferation and Wound
Healing in Mice.
AB - Thymosin beta4 (Tbeta4) is a peptide that is known to play important roles in
protection, regeneration, and remodeling of injured tissues in humans, and that
shows great promise in a range of clinical applications. However, current
strategies to Tbeta4 are insufficient to meet growing demand and have a number of
limitations. In this current study we investigated whether expression of
recombinant Tbeta4 in plants, specifically in tobacco (Nicotiana tabacum) leaves,
represents an effective approach. To address this question, a 168 bp Tbeta4 gene
optimized for tobacco codon usage bias was constitutively expressed in tobacco as
a 4-unit repeat concatemer, fused to a polyhistidine tag. Quantitative polymerase
chain reaction and Western blot analyses were used to verify 4*Tbeta4 expression
in 14 transgenic tobacco lines and enzyme-linked immunosorbent assay analysis
indicated 4*Tbeta4 protein concentrations as high as 3 MUg/g of fresh weight in
the leaves. We observed that direct administration of tobacco-derived Tbeta4 was
more effective than Tbeta4 either obtained commercially or derived from
expression in Escherichia coli at promoting splenocyte proliferation in vitro and
wound healing in mice through an endothelial migration assay. This study provides
new insights into the development of plant-derived therapeutic proteins and their
application by direct administration.
PMID- 27493954
TI - Cognitive Rehabilitation in Patients with Gliomas and Other Brain Tumors: State
of the Art.
AB - Disease prognosis is very poor in patients with brain tumors. Cognitive deficits
due to disease or due to its treatment have an important weight on the quality of
life of patients and caregivers. Studies often take into account quality of life
as a fundamental element in the management of disease and interventions have been
developed for cognitive rehabilitation of neuropsychological deficits with the
aim of improving the quality of life and daily-life autonomy of patients. In this
literature review, we will consider the published studies of cognitive
rehabilitation over the past 20 years.
PMID- 27493955
TI - Historical ESWT Paradigms Are Overcome: A Narrative Review.
AB - Extracorporeal Shock Wave Therapy (ESWT) is a conservative treatment modality
with still growing interest in musculoskeletal disorders. This narrative review
aims to present an overview covering 20-year development in the field of
musculoskeletal ESWT. Eight historical paradigms have been identified and put
under question from a current perspective: energy intensity, focus size,
anesthesia, imaging, growth plates, acuteness, calcifications, and number of
sessions. All paradigms as set in a historical consensus meeting in 1995 are to
be revised. First, modern musculoskeletal ESWT is divided into focused and radial
technology and the physical differences are about 100-fold with respect to the
applied energy. Most lesions to be treated are easy to reach and clinical
focusing plays a major role today. Lesion size is no longer a matter of concern.
With the exception of nonunion fractures full, regional, or even local anesthesia
is not helpful in musculoskeletal indications. Juvenile patients can also
effectively be treated without risk of epiphyseal damage. Further research is
needed to answer the question about if and which acute injuries can be managed
effectively. Treatment parameters like the number of sessions are still relying
on empirical data and have to be further elucidated.
PMID- 27493956
TI - Efficacy of Immediate Switching from Bicalutamide to Flutamide as Second-Line
Combined Androgen Blockade.
AB - We determined whether prostate specific antigen (PSA) would decrease with
immediate antiandrogen switching from bicalutamide (BCL) to flutamide (FLT) in
patients receiving combined androgen blockade for advanced prostate cancer. From
2002 to 2006, 20 patients who showed PSA failure after first-line hormonal
therapy with a luteinizing hormone-release hormone (LH-RH) agonist and BCL were
enrolled. All patients were immediately switched from BCL to FLT, administered
with an LH-RH agonist, as second-line combined androgen blockade (CAB). We
evaluated the PSA response to second-line CAB. Eight patients (40%) were
responsive, showing PSA decreases of at least 50%. The median (range) duration of
the PSA response was 18.4 (3-26) months. Second-line CAB using FLT was effective
in 40% of patients who received first-line CAB using BCL. The lower Gleason
scores at the initial prostate biopsy probably reflect the response to second
line CAB. Responders showed significantly better OS and CSS in the determination
of any PSA decline and 40% PSA decline. The median OS duration in nonresponders
and responders (40% PSA decline) was 1433 days versus 3617 days. It is concluded
that an immediate switch from BCL to FLT is effective for some CRPC patients
after first-line CAB using BCL.
PMID- 27493957
TI - Evaluation of Implant Collar Surfaces for Marginal Bone Loss: A Systematic Review
and Meta-Analysis.
AB - Background. It is important to understand the influence of different collar
designs on peri-implant marginal bone loss, especially in the critical area.
Objectives. The purpose of the present systematic review and meta-analysis was to
compare dental implants with different collar surfaces, evaluating marginal bone
loss and survival rates of implants. Methods. Eligibility criteria included
clinical human studies, randomized controlled trials, and prospective and
retrospective studies, which evaluated dental implants with different collar
surface in the same study. Results. Twelve articles were included, with a total
of 492 machined, 319 rough-surfaced, and 352 rough-surfaced microthreaded neck
implants. There was less marginal bone loss at implants with rough-surfaced and
rough-surfaced microthreaded neck than at machined-neck implants (difference in
means: 0.321, 95% CI: 0.149 to 0.493; p < 0.01). Conclusion. Rough and rough
surfaced microthreaded implants are considered a predictable treatment for
preserving early marginal bone loss.
PMID- 27493958
TI - Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its
Clinical Significance.
AB - A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a
member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We
analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and
gastric cancer cell lines. We also examined the relationship between ADAMTS8
expression and methylation and clinicopathologic features. The results showed
that the significant downregulation of ADAMTS8 mRNA expression was observed in
gastric cancer cell lines and tissues, and its expression was related to invasive
depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell
lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens.
ADAMTS8 mRNA expression was significantly lower in methylated primary gastric
tumors. A significant association was found between ADAMTS8 methylation status
and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression
was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after
treatment with 5-aza-2'-deoxycytidine. Thus, our results demonstrate that
expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is
frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased
expression in gastric cancer and may play an important role in the invasion and
metastasis of gastric cancer.
PMID- 27493959
TI - Distribution of Triamcinolone Acetonide after Intravitreal Injection into
Silicone Oil-Filled Eye.
AB - There is increasing use of the vitreous cavity as a reservoir for drug delivery.
We study the intraocular migration and distribution of triamcinolone acetonide
(TA) after injection into silicone oil tamponade agent during and after
vitrectomy surgery ex vivo (pig eye) and in vitro (glass bottle). For ex vivo
assessment, intraocular migration of TA was imaged using real-time FLASH MRI
scans and high-resolution T2W imaging and the in vitro model was monitored
continuously with a video camera. Results of the ex vivo experiment showed that
the TA droplet sank to the interface of silicone oil and aqueous almost
immediately after injection and remained inside the silicone oil bubble for as
long as 16 minutes. The in vitro results showed that, after the shrinkage of the
droplet, TA gradually precipitated leaving only a lump of whitish crystalline
residue inside the droplet for about 100 minutes. TA then quickly broke the
interface and dispersed into the underlying aqueous within 15 seconds, which may
result in a momentary increase of local TA concentration in the aqueous portion
and potentially toxic to the retina. Our study suggests that silicone oil may not
be a good candidate as a drug reservoir for drugs like TA.
PMID- 27493960
TI - Quantitative In Vitro and In Vivo Evaluation of Intestinal and Blood-Brain
Barrier Transport Kinetics of the Plant N-Alkylamide Pellitorine.
AB - Objective. To evaluate the gut mucosa and blood-brain barrier (BBB)
pharmacokinetic permeability properties of the plant N-alkylamide pellitorine.
Methods. Pure pellitorine and an Anacyclus pyrethrum extract were used to
investigate the permeation of pellitorine through (1) a Caco-2 cell monolayer,
(2) the rat gut after oral administration, and (3) the BBB in mice after
intravenous and intracerebroventricular administration. A validated bioanalytical
UPLC-MS(2) method was used to quantify pellitorine. Results. Pellitorine was able
to cross the Caco-2 cell monolayer from the apical-to-basolateral and from the
basolateral-to-apical side with apparent permeability coefficients between 0.6 .
10(-5) and 4.8 . 10(-5) cm/h and between 0.3 . 10(-5) and 5.8 . 10(-5) cm/h,
respectively. In rats, a serum elimination rate constant of 0.3 h(-1) was
obtained. Intravenous injection of pellitorine in mice resulted in a rapid and
high permeation of pellitorine through the BBB with a unidirectional influx rate
constant of 153 MUL/(g.min). In particular, 97% of pellitorine reached the brain
tissue, while only 3% remained in the brain capillaries. An efflux transfer
constant of 0.05 min(-1) was obtained. Conclusion. Pellitorine shows a good gut
permeation and rapidly permeates the BBB once in the blood, indicating a possible
role in the treatment of central nervous system diseases.
PMID- 27493962
TI - An Effective and Feasible Method, "Hammering Technique," for Percutaneous
Fixation of Anterior Column Acetabular Fracture.
AB - Objective. The objective of this study was to evaluate the effectiveness and
advantages of percutaneous fixation of anterior column acetabular fracture with
"hammering technique." Materials and Methods. We retrospectively reviewed 16
patients with percutaneous fixation of anterior column acetabular fracture with
"hammering technique." There were 11 males and 5 females with an average age of
38.88 years (range: 24-54 years) in our study. Our study included 7 nondisplaced
fractures, 6 mild displaced fractures (<2 mm), and 5 displaced fractures (>2 mm).
The mean time from injury to surgery was 4.5 days (range: 2-7 days). Results. The
average of operation time was 27.56 minutes (range: 15-45 minutes), and the mean
blood loss was 55.28 mL (range: 15-100 mL). The mean fluoroscopic time was 54.78
seconds (range: 40-77 seconds). The first pass of the guide wire was acceptable
without cortical perforation or intra-articular perforation in 88.89% (16/18) of
the procedures, and the second attempt was in 11.11% (2/18). Conclusion. Our
study suggested that percutaneous fixation of anterior column acetabular fracture
with "hammering technique" acquired satisfying surgical and clinical outcomes. It
may be an alternative satisfying treatment for percutaneous fixation of anterior
column acetabular fracture by 2D fluoroscopy using a C-arm with less fluoroscopic
time.
PMID- 27493963
TI - Effects of a Lifestyle-Based Physical Activity Intervention on Medical
Expenditure in Japanese Adults: A Community-Based Retrospective Study.
AB - Background. This study aimed to investigate whether a lifestyle-based physical
activity program could contribute to reduced medical expenditure. Methods. The
study participants were 60 adults aged 63.1 (standard deviation, 4.4) years in
the intervention group; the case-control group consisted of 300 adults who were
randomly selected from Japan's national health insurance system. This community
based retrospective study incorporated a 3-year follow-up. Results. The total and
outpatient medical expenditure in the intervention group were significantly lower
than in the control group: total expenditure, $US640.4/year; outpatient
expenditure, $369.1/year. The odds ratio for outpatient visiting was 6.47-fold
higher in the control than in the intervention group. Conclusion. Our study
suggests that a health program to promote physical activity can result in reduced
total medical expenditure, outpatient medical expenditure, and possibly also
inpatient medical expenditure.
PMID- 27493961
TI - The Epithelial Sodium Channel and the Processes of Wound Healing.
AB - The epithelial sodium channel (ENaC) mediates passive sodium transport across the
apical membranes of sodium absorbing epithelia, like the distal nephron, the
intestine, and the lung airways. Additionally, the channel has been involved in
the transduction of mechanical stimuli, such as hydrostatic pressure, membrane
stretch, and shear stress from fluid flow. Thus, in vascular endothelium, it
participates in the control of the vascular tone via its activity both as a
sodium channel and as a shear stress transducer. Rather recently, ENaC has been
shown to participate in the processes of wound healing, a role that may also
involve its activities as sodium transporter and as mechanotransducer. Its
presence as the sole channel mediating sodium transport in many tissues and the
diversity of its functions probably underlie the complexity of its regulation.
This brief review describes some aspects of ENaC regulation, comments on evidence
about ENaC participation in wound healing, and suggests possible regulatory
mechanisms involved in this participation.
PMID- 27493964
TI - Homocysteine Levels in Parkinson's Disease: Is Entacapone Effective?
AB - Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with
Parkinson's disease (PD) as a consequence of levodopa methylation via catechol-O
methyltransferase (COMT). Results from previous studies that assessed the effect
of COMT inhibitors on levodopa-induced hyperhomocysteinemia are conflicting. We
aimed to evaluate the effects of levodopa and entacapone on plasma Hcy levels. A
hundred PD patients were enrolled to the study and divided into three treatment
groups (group I: levodopa and/or dopamine agonists; group II: levodopa,
entacapone, and/or a dopamine agonist; and group III: dopamine agonist alone). We
measured the serum B12, folic acid, and Hcy levels in all patients. There were no
statistically significant differences between groups in terms of modified Hoehn
and Yahr stages, Unified Parkinson's Disease Rating Scale II/III, Standardized
Mini-Mental Test scores, and serum vitamin B12 and folic acid levels. Plasma
median Hcy levels were found above the normal laboratory values in groups I and
II, but they were normal in group III. However, there was no statistically
significant difference in plasma Hcy levels between groups. Our results showed
that levodopa treatment may cause a slight increase in the Hcy levels in PD
compared with dopamine agonists and that COMT inhibitors may not have a
significant effect on preventing hyperhomocysteinemia.
PMID- 27493965
TI - In Vivo Corneal Biomechanical Properties with Corneal Visualization Scheimpflug
Technology in Chinese Population.
AB - Purpose. To determine the repeatability of recalculated corneal visualization
Scheimpflug technology (CorVis ST) parameters and to study the variation of
biomechanical properties and their association with demographic and ocular
characteristics. Methods. A total of 783 healthy subjects were included in this
study. Comprehensive ophthalmological examinations were conducted. The
repeatability of the recalculated biomechanical parameters with 90 subjects was
assessed by the coefficient of variation (CV) and intraclass correlation
coefficient (ICC). Univariate and multivariate linear regression models were used
to identify demographic and ocular factors. Results. The repeatability of the
central corneal thickness (CCT), deformation amplitude (DA), and first/second
applanation time (A1/A2-time) exhibited excellent repeatability (CV% <= 3.312%
and ICC >= 0.929 for all measurements). The velocity in/out (V in/out), highest
concavity- (HC-) radius, peak distance (PD), and DA showed a normal distribution.
Univariate linear regression showed a statistically significant correlation
between V in, V out, DA, PD, and HC-radius and IOP, CCT, and corneal volume,
respectively. Multivariate analysis showed that IOP and CCT were negatively
correlated with V in, DA, and PD, while there was a positive correlation between
V out and HC-radius. Conclusion. The ICCs of the recalculated parameters, CCT,
DA, A1-time, and A2-time, exhibited excellent repeatability. IOP, CCT, and
corneal volume significantly influenced the biomechanical properties of the eye.
PMID- 27493966
TI - Energetic Assessment of the Nonexercise Activities under Free-Living Conditions.
AB - Nonexercise activities (NAs) are common types of physical activity in daily life
and critical component in energy expenditure. However, energetic assessment of
NA, particularly in free-living subjects, is a technical challenge. In this
study, mechanical modeling and portable device were used to evaluate five common
types of NA in daily life: sit to stand, lie to sit, bowing while standing,
squat, and right leg over left. A human indirect calorimeter was used to measure
the activity energy expenditure of NA. Mechanical work and mechanical efficiency
of NA were calculated for mechanical modeling. Thirty-two male subjects were
recruited for the study (20 subjects for the development of models and 12
subjects for evaluation of models). The average (mean +/- SD) mechanical work of
5 NAs was 2.31 +/- 0.50, 2.88 +/- 0.57, 1.75 +/- 0.55, 3.96 +/- 1.25, and 1.25 +/
0.51 J/kg.m, respectively. The mean mechanical efficiencies of those activities
were 22.0 +/- 3.3%, 26.5 +/- 5.1%, 19.8 +/- 3.7%, 24.0 +/- 5.5%, and 26.3 +/-
5.5%. The activity energy expenditure estimated by the models was not
significantly different from the measurements by the calorimeter (p > 0.05) with
accuracies of 102.2 +/- 20.7%, 103.7 +/- 25.8%, 105.6 +/- 14.6%, 101.1 +/- 28.0%,
and 95.8 +/- 20.7%, respectively, for those activities. These findings suggest
that the mechanical models combined with a portable device can provide an
alternative method for the energetic analysis of nonexercise activities under
free-living condition.
PMID- 27493967
TI - A Shortest Dependency Path Based Convolutional Neural Network for Protein-Protein
Relation Extraction.
AB - The state-of-the-art methods for protein-protein interaction (PPI) extraction are
primarily based on kernel methods, and their performances strongly depend on the
handcraft features. In this paper, we tackle PPI extraction by using
convolutional neural networks (CNN) and propose a shortest dependency path based
CNN (sdpCNN) model. The proposed method (1) only takes the sdp and word embedding
as input and (2) could avoid bias from feature selection by using CNN. We
performed experiments on standard Aimed and BioInfer datasets, and the
experimental results demonstrated that our approach outperformed state-of-the-art
kernel based methods. In particular, by tracking the sdpCNN model, we find that
sdpCNN could extract key features automatically and it is verified that
pretrained word embedding is crucial in PPI task.
PMID- 27493968
TI - In Vitro Bioactivity Study of RGD-Coated Titanium Alloy Prothesis for Revision
Total Hip Arthroplasty.
AB - Total hip arthroplasty (THA) is a common procedure for the treatment of end-stage
hip joint disease, and the demand for revision THA will double by 2026. Ti6Al4V
(Titanium, 6% Aluminum, and 4% Vanadium) is a kind of alloy commonly used to make
hip prothesis. To promote the osseointegration between the prothesis and host
bone is very important for the revision THA. The peptide Arg-Gly-Asp (RGD) could
increase cell attachment and has been used in the vascular tissue engineering. In
this study, we combined the RGD with Ti6Al4V alloy using the covalent cross
linking method to fabricate the functional Ti6Al4V alloy (FTA). The distribution
of RGD oligopeptide on the FTA was even and homogeneous. The FTA scaffolds could
promote mouse osteoblasts adhesion and spreading. Furthermore, the result of RT
qPCR indicated that the FTA scaffolds were more beneficial to osteogenesis, which
may be due to the improvement of osteoblast adhesion by the RGD oligopeptide
coated on FTA. Overall, the FTA scaffolds developed herein pave the road for
designing and building more efficient prothesis for osseointegration between the
host bone and prothesis in revision THA.
PMID- 27493969
TI - Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome
Analysis.
AB - Atherosclerosis can be regarded as a chronic inflammatory state, in which
macrophages play different and important roles. Phagocytic proinflammatory cells
populate growing atherosclerotic lesions, where they actively participate in
cholesterol accumulation. Moreover, macrophages promote formation of complicated
and unstable plaques by maintaining proinflammatory microenvironment. At the same
time, anti-inflammatory macrophages contribute to tissue repair and remodelling
and plaque stabilization. Macrophages therefore represent attractive targets for
development of antiatherosclerotic therapy, which can aim to reduce monocyte
recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate
anti-inflammatory responses and cholesterol efflux. More studies are needed,
however, to create a comprehensive classification of different macrophage
phenotypes and to define their roles in the pathogenesis of atherosclerosis. In
this review, we provide an overview of the current knowledge on macrophage
diversity, activation, and plasticity in atherosclerosis and describe macrophage
based cellular tests for evaluation of potential antiatherosclerotic substances.
PMID- 27493970
TI - The Impact of Type 2 Diabetes on the Efficacy of ADP Receptor Blockers in
Patients with Acute ST Elevation Myocardial Infarction: A Pilot Prospective
Study.
AB - Background. The aim of this study was to validate the impact of type 2 diabetes
(T2D) on the platelet reactivity in patients with acute ST elevation myocardial
infarction (STEMI) treated with adenosine diphosphate (ADP) receptor blockers.
Methods. A pilot prospective study was performed. Totally 67 patients were
enrolled. 21 patients had T2D. Among all study population, 33 patients received
clopidogrel and 34 patients received prasugrel. The efficacy of ADP receptor
blocker therapy had been tested in two time intervals using light transmission
aggregometry with specific inducer and vasodilator-stimulated phosphoprotein
phosphorylation (VASP-P) flow cytometry assay. Results. There were no significant
differences in platelet aggregability among T2D and nondiabetic (ND) group. The
platelet reactivity index of VASP-P did not differ significantly between T2D and
ND group (59.4 +/- 30.9% versus 60.0 +/- 25.2% and 33.9 +/- 25.3% versus 38.6 +/-
29.3% in second testing). The number of ADP receptor blocker nonresponders did
not differ significantly between T2D and ND patients. The time interval from ADP
receptor blocker loading dosing to the blood sampling was similar in T2D and ND
patients in both examinations. Conclusion. This prospective study did not confirm
the higher platelet reactivity and higher prevalence of ADP receptor blocker
nonresponders in T2D acute STEMI patients.
PMID- 27493971
TI - HLA-E(*)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic
Lung Allograft Dysfunction Occurrence.
AB - Lung transplantation (LTx) is a valid therapeutic option for selected patients
with end-stage lung disease. HLA-E seems to play a major role in the immune
response to different viral infections and to affect transplantation outcome, in
Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles,
HLA-E(*)01:01 and HLA-E(*)01:03, have functional differences, involving relative
peptide affinity, cell surface expression, and potential lytic activity of NK
cells. The aim of this retrospective study was to determine the impact of these
two alleles for LTx recipients on anti-HLA alloimmunization risk, overall
survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who
underwent LTx from 1998 to 2010 in a single transplantation center. In univariate
analysis, both HLA-E homozygous states were associated with impaired overall
survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate
analysis, HLA-E(*)01:03 allele showed increased CLAD occurrence when compared to
homozygous HLA-E(*)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E
allele did not affect pathogen infection or the production of de novo DSA. This
retrospective study shows an uninvestigated, deleterious association of HLA-E
alleles with LTx and requires verification using a larger cohort.
PMID- 27493972
TI - Actions of Thyroid Hormone Analogues on Chemokines.
AB - The extracellular domain of plasma membrane integrin alphavbeta3 contains a
receptor for thyroid hormone (L-thyroxine, T4; 3,5,3'-triiodo-L-thyronine, T3);
this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4.
Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is
a chemokine relevant to inflammatory processes in the CNS that are microglia
dependent but also important to normal brain development. Expression of the
CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate
fractalkine expression. Independently of its specific receptor (CX3CR1),
fractalkine binds to alphavbeta3 at a site proximal to the thyroid hormone-tetrac
receptor and changes the physical state of the integrin. Tetrac also affects
expression of the genes for other CNS-relevant chemokines, including CCL20,
CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are
important to vascularity of the brain, particularly of the choroid plexus, to
inflammatory processes in the CNS and, in certain cases, to neuroprotection.
Thyroid hormones are known to contribute to regulation of each of these CNS
functions. We propose that actions of thyroid hormone and hormone analogues on
chemokine gene expression contribute to regulation of inflammatory processes in
brain and of brain blood vessel formation and maintenance.
PMID- 27493974
TI - Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain
Significance and Multiple Myeloma: In Search of a Role.
AB - The frequency and function of regulatory T-cells (Tregs) in multiple myeloma (MM)
are still matter of debate. The percentage and absolute number of circulating
Tregs (CD4(+)CD25(+high density)CD127(-/low density)) from 39 patients with
untreated MM and 44 patients with monoclonal gammopathies of uncertain
significance (MGUS) were tested and compared with 20 healthy subjects as
controls. The mean percentage number of circulating Tregs was 2.1% +/- 1.0
(range 0.75-6.1%) in MM patients; 2.1% +/- 0.9 (range 0.3-4.4%) in MGUS; and
1.5% +/- 0.4 (range 0.9-2.1%) in controls (p ns). Mean absolute number of Tregs
was 36.3/MUL +/- 23.7 (range 6.7-149/MUL) in MM; 38.8/MUL +/- 19.1 (range 4.3
87/MUL) in MGUS; and 39.4/MUL +/- 12.5 (range 18-63/MUL) in controls (p ns).
After a median follow-up of 38 months, 5 MGUS and 2 smoldering MM (SMM)
transformed into overt MM; however Tregs number did not predict this evolution.
With respect to MM patients and after a median follow-up of 33 months, Tregs did
not show any significant correlation with main clinical and laboratory
characteristics. Finally, from a functional point of view, Tregs displayed an
effective suppressor function, irrespective of disease status. This study
indicates that the number of circulating Tregs does not differ in different
monoclonal gammopathies and normal subjects and do not correlate with clinical
features of MM.
PMID- 27493973
TI - An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment.
AB - Inflamm-aging is a challenging and promising new branch of aging-related research
fields that includes areas such as immunosenescence. Increasing evidence
indicates that inflamm-aging is intensively associated with many aging diseases,
such as Alzheimer's disease, atherosclerosis, heart disease, type II diabetes,
and cancer. Mounting studies have focused on the role of inflamm-aging in disease
progression and many advances have been made in the last decade. However, the
underlying mechanisms by which inflamm-aging affects pathological changes and
disease development are still unclear. Here, we review studies of inflamm-aging
that explore the concept, pathological features, mechanisms, intervention, and
the therapeutic strategies of inflamm-aging in disease progression.
PMID- 27493975
TI - Ovarian Carcinoma With Isolated Spinal Cord Metastasis.
AB - Ovarian cancer metastasis to the spinal cord is quite rare, and few case reports
have been published previously. Herein, we present a case of a patient who was
treated for ovarian cancer and was thought to be disease free for 17 months, then
presented with lower limb weakness. She was found to have a T11-T12 metastatic
intramedullary spinal cord lesion. On pathology, the diagnosis of metastatic
ovarian adenocarcinoma was made. This report highlights the importance of
maintaining a low threshold for ovarian cancer metastases to the spinal cord when
patients present with neurologic sequelae, even in the setting of normal
laboratory values, as early detection can prevent permanent neurological
consequences.
PMID- 27493976
TI - Pseudoradial Nerve Palsy Caused by Acute Ischemic Stroke.
AB - Pseudoperipheral palsy has been used to characterize isolated monoparesis
secondary to stroke. Isolated hand nerve palsy is a rare presentation for acute
cerebral stroke. Our patient presented with clinical features of typical
peripheral radial nerve palsy and a normal computed tomography scan of the head,
which, without a detailed history and neurological examination, could have been
easily misdiagnosed as a peripheral nerve lesion deferring further investigation
for a stroke. We stress the importance of including cerebral infarction as a
critical differential diagnosis in patients presenting with sensory-motor deficit
in an isolated peripheral nerve pattern. A good history and physical exam can
differentiate stroke from peripheral neuropathy as the cause of radial nerve
palsy.
PMID- 27493977
TI - Prosthetic Arteriovenous Graft Contact Dermatitis Masquerading as an
Arteriovenous Graft Infection in a Hemodialysis Patient.
AB - Prosthetic arteriovenous (AV) graft is the second most common vascular access of
choice in hemodialysis patients. Rare complications of such grafts are
increasingly seen due to rising population of patients on hemodialysis.
Infections and thrombosis are the most common complications. Though metallic
implants are known to cause hypersensitivity skin reactions, prosthetic AV grafts
are rarely known to cause such kind of reactions due to inert nature of materials
used in their preparation. We present a case of 54-year-old male who developed
contact dermatitis after AV graft creation which was mistreated initially as
infection.
PMID- 27493978
TI - Tear biomarkers for keratoconus.
AB - Keratoconus is a progressive corneal thinning, ectatic condition, which affects
vision. Recent advances in corneal topography measurements has helped advance
proper diagnosis of this condition and increased research and clinical interests
in the disease etiopathogenesis. Considerable progress has been achieved in
understanding the progression of the disease and tear fluid has played a major
role in the progress. This review discusses the importance of tear fluid as a
source of biomarker for keratoconus and how advances in technology have helped
map the complexity of tears and thereby molecular readouts of the disease.
Expanding knowledge of the tear proteome, lipidome and metabolome opened up new
avenues to study keratoconus and to identify probable prognostic or diagnostic
biomarkers for the disease. A multidimensional approach of analyzing tear fluid
of patients layering on proteomics, lipidomics and metabolomics is necessary in
effectively decoding keratoconus and thereby identifying targets for its
treatment.
PMID- 27493979
TI - Dimensions of similarity in the mental lexicon.
AB - During language production planning, multiple candidate representations are
implicitly activated prior to articulation. Lexical representations that are
phonologically related to the target (phonological neighbors) are known to
influence phonetic properties of the target word. However, the question of which
dimensions of phonological similarity contribute to such lexical-phonetic effects
remains unanswered. In the present study, we reanalyze phonetic data from a
previous study, examining the contrasting predictions of different definitions of
phonological similarity. Our results suggest that similarity at the level of
position-specific phonological segments best predicts the influence of neighbor
activation on phonetic properties of initial consonants.
PMID- 27493980
TI - Methodology for high-yield acquisition of functional near-infrared spectroscopy
data from alert, upright infants.
AB - Functional near-infrared spectroscopy (fNIRS) research to date has tended to
publish group-averaged rather than individual infant data due to normative basic
research goals. Acquisition of individual infant time courses holds interest,
however, both for cognitive science and particularly for clinical applications.
Infants are more difficult to study than adults as they cannot be instructed to
remain still. In addressing this, upright infants pose several associated
complications for the researcher. We identified and optimized the factors that
affect the quality of fNIRS data from individual 6- to 9-month-old infants
exposed to a visual stimulation paradigm. The fNIRS headpiece was reconfigured to
reduce inertia, increase comfort, and improve conformity to the head, while
preserving fiber density to avoid missing the visual cortex activation. The
visual-stimulation protocol was modified to keep the attention of infants
throughout the measurement, thus helping to reduce motion artifacts. Adequate
optical contact was verified by checking power levels before each measurement. By
revising our experimental process and our data rejection criteria to prioritize
good optical contact, we report for the first time usable hemodynamic data from
83% of infants and that two-thirds of infants produced a statistically
significant fNIRS response.
PMID- 27493981
TI - Subject-specific four-dimensional liver motion modeling based on registration of
dynamic MRI.
AB - Magnetic resonance-guided high intensity focused ultrasound treatment of the
liver is a promising noninvasive technique for ablation of liver lesions. For the
technique to be used in clinical practice, however, the issue of liver motion
needs to be addressed. A subject-specific four-dimensional liver motion model is
presented that is created based on registration of dynamically acquired magnetic
resonance data. This model can be used for predicting the tumor motion trajectory
for treatment planning and to indicate the tumor position for treatment guidance.
The performance of the model was evaluated on a dynamic scan series that was not
used to build the model. The method achieved an average Dice coefficient of 0.93
between the predicted and actual liver profiles and an average vessel
misalignment of 3.0 mm. The model performed robustly, with a small variation in
the results per subject. The results demonstrate the potential of the model to be
used for MRI-guided treatment of liver lesions. Furthermore, the model can
possibly be applied in other image-guided therapies, for instance radiotherapy of
the liver.
PMID- 27493982
TI - Design of a practical model-observer-based image quality assessment method for x
ray computed tomography imaging systems.
AB - The use of a channelization mechanism on model observers not only makes mimicking
human visual behavior possible, but also reduces the amount of image data needed
to estimate the model observer parameters. The channelized Hotelling observer
(CHO) and channelized scanning linear observer (CSLO) have recently been used to
assess CT image quality for detection tasks and combined detection/estimation
tasks, respectively. Although the use of channels substantially reduces the
amount of data required to compute image quality, the number of scans required
for CT imaging is still not practical for routine use. It is our desire to
further reduce the number of scans required to make CHO or CSLO an image quality
tool for routine and frequent system validations and evaluations. This work
explores different data-reduction schemes and designs an approach that requires
only a few CT scans. Three different kinds of approaches are included in this
study: a conventional CHO/CSLO technique with a large sample size, a conventional
CHO/CSLO technique with fewer samples, and an approach that we will show requires
fewer samples to mimic conventional performance with a large sample size. The
mean value and standard deviation of areas under ROC/EROC curve were estimated
using the well-validated shuffle approach. The results indicate that an 80% data
reduction can be achieved without loss of accuracy. This substantial data
reduction is a step toward a practical tool for routine-task-based QA/QC CT
system assessment.
PMID- 27493983
TI - Usage and Attitudes Towards Natural Remedies and Homeopathy in General
Pediatrics: A Cross-Country Overview.
AB - In order to better understand the global approach and country differences in
physicians' usage, knowledge, and attitudes towards natural remedies and
homeopathy in pediatric practice, an online survey involving 582 general
pediatricians and general practitioners treating pediatric diseases was conducted
in 6 countries. Overall, 17% of the pediatric prescriptions refer to phytotherapy
and 15% refer to homeopathic preparations. Natural remedies and homeopathic
preparations are more frequently used in upper respiratory tract infections,
infant colic, sleep disturbances, and recurrent infections. In the majority of
cases, they are used together with chemical drugs. Both treatment options are
typically used if parents are concerned about side effects of conventional drugs
or prefer natural remedies for themselves. Physicians express high interest in
natural remedies and homeopathy; however, their knowledge is variable. Lack of
proven efficacy, knowledge on mechanism of action, and information on indications
are main factors that limit their usage.
PMID- 27493984
TI - The Effectiveness and Safety of a Homeopathic Medicinal Product in Pediatric
Upper Respiratory Tract Infections With Fever: A Randomized Controlled Trial.
AB - We investigated the clinical effectiveness of a homeopathic add-on therapy in a
pediatric subpopulation with upper respiratory tract infections (URTI) in a
randomized, controlled, multinational clinical trial. Patients received either on
demand symptomatic standard treatment (ST-group) or the same ST plus a
homeopathic medication (Influcid; IFC-group) for 7 days. Outcome assessment was
based on symptom and fever resolution and the Wisconsin Upper Respiratory Symptom
Survey-21 (WURSS-21). A total of 261 pediatric (<12 years) patients (130 IFC
group; 131 ST-group) were recruited in Germany and the Ukraine. The IFC-group
used less symptomatic medication, symptoms resolved significantly earlier (P =
.0001), had higher proportions of fever-free children from day 3 onwards, and the
WURSS-assessed global disease severity was significantly less (P < .0001) during
the entire URTI episode. One adverse event (vomiting) was possibly related to
IFC. IFC as add-on treatment in pediatric URTI reduced global disease severity,
shortened symptom resolution, and was safe in use.
PMID- 27493985
TI - A Study to Determine if Addition of Palatal Petechiae to Centor Criteria Adds
More Significance to Clinical Diagnosis of Acute Strep Pharyngitis in Children.
AB - Objective. A study to determine if addition of palatal petechiae to Centor
criteria adds more value for clinical diagnosis of acute strep pharyngitis in
children. Hypothesis. In children, Centor Criteria does not cover all the
symptoms and signs of acute strep pharyngitis. We hypothesize that addition of
palatal petechiae to Centor Criteria will increase the possibility of clinical
diagnosis of group A streptococcal pharyngitis in children. Methods. One hundred
patients with a complaint of sore throat were enrolled in the study. All the
patients were examined clinically using the Centor Criteria. They were also
examined for other signs and symptoms like petechial lesions over the palate,
abdominal pain, and skin rash. All the patients were given rapid strep tests, and
throat cultures were sent. No antibiotics were given until culture results were
obtained. Results. The sample size was 100 patients. All 100 had fever, sore
throat, and erythema of tonsils. Twenty of the 100 patients had tonsillar
exudates, 85/100 had tender anterior cervical lymph nodes, and 86/100 had no
cough. In total, 9 out of the 100 patients had positive throat cultures. We
observed that petechiae over the palate, a very significant sign, is not included
in the Centor Criteria. Palatal petechiae were present in 8 out of the 100
patients. Six out of these 8 with palatal petechiae had positive throat culture
for strep (75%). Only 7 out of 20 with exudates had positive strep culture.
Sixteen out of the 100 patients had rapid strep test positive. Those 84/100 who
had negative rapid strep also had negative throat culture. Statistics. We used
Fisher's exact test, comparing throat culture positive and negative versus
presence of exudates and palatal hemorrhages with positive and negative throat
cultures and the resultant P value <.0001. Conclusion. Our study concludes that
addition of petechiae over the palate to Centor Criteria will increase the
possibility of diagnosing acute group A streptococcal pharyngitis in children.
PMID- 27493986
TI - A 15-Year-Old Boy With Facial Palsy and Progressive Hearing Loss.
PMID- 27493987
TI - Local coverage determination policy and the use of stereotactic body radiation
therapy for prostate cancer.
AB - INTRODUCTION: Local coverage determinations (LCDs) are local decisions that
regulate healthcare coverage. We evaluated the impact of LCDs as well as patient,
tumor, and market characteristics on the adoption of stereotactic body radiation
therapy (SBRT) for prostate cancer. METHODS: Using Surveillance, Epidemiology,
and End Results (SEER)-Medicare, we identified men treated with SBRT, intensity
modulated radiotherapy (IMRT), and robotic prostatectomy. We compared
demographics, clinical characteristics, and market factors among these three
treatments. Our primary exposure was LCD policy; using the Medicare Coverage
Database, we categorized LCDs as favorable (SBRT covered), neutral (SBRT covered
in the context of a clinical trial or registry), unfavorable (SBRT not covered),
or absent (i.e., SBRT not governed by an LCD at the time of treatment). We fit a
multivariable multinomial logistic regression model and generated predicted
probabilities to examine the relation between LCDs and SBRT. RESULTS: During this
early period of SBRT adoption, IMRT was the most common of the three treatments
followed by robotic prostatectomy and then SBRT. SBRT use was high when governed
by favorable and neutral LCDs and lowest when governed by unfavorable LCDs.
Compared with favorable LCDs, areas where LCDs were absent were associated with
higher SBRT use compared with IMRT (odds ratio [OR] 1.56; 95%CI, 1.07-2.25) and
robotic prostatectomy (OR 1.84; 95%CI, 1.25-2.69). CONCLUSIONS: When present,
LCDs appear to regulate early SBRT adoption, but, when absent, are associated
with increased SBRT use. Although SBRT use was uncommon, it varied across a wide
range of patient, tumor, and market characteristics.
PMID- 27493988
TI - Intestinal Parasite Profile in the Stool of HIV Positive Patients in relation to
Immune Status and Comparison of Various Diagnostic Techniques with Special
Reference to Cryptosporidium at a Tertiary Care Hospital in South India.
AB - Acquired immunodeficiency syndrome and related opportunistic infections are a
significant cause of morbidity and mortality in susceptible population. This
study aims to negate the paucity of data regarding the relation between CD4
levels, prevalence of enteric parasites, and the outcome of treatment with HAART
(highly active antiretroviral therapy) and Cotrimoxazole in Kerala, India.
Multiple stool samples from 200 patients in a cross-sectional study were
subjected to microscopy and Cryptosporidium stool antigen ELISA. Parasites were
identified in 18 samples (9%). Cystoisospora and Cryptosporidium spp. were seen
in 9 cases (4.5%) and 5 cases (2.5%), respectively. Microsporidium spores and
Chilomastix mesnili cysts were identified in 1 case each (0.5% each). Seven cases
of Cystoisospora diarrhoea recovered after treatment with Cotrimoxazole.
Diarrhoea due to Cryptosporidium spp. in all 5 cases subsided after immune
reconstitution with HAART. This study concludes that a positive association was
seen between low CD4 count (<200 cells/MUL) and overall parasite positivity (P
value < 0.01). ELISA is a more sensitive modality for the diagnosis of
Cryptosporidium diarrhoea. Chilomastix mesnili, generally considered a
nonpathogen, may be a cause of diarrhoeal disease in AIDS. Immune reconstitution
and Cotrimoxazole prophylaxis remain to be the best therapeutic approach in AIDS
related diarrhoea.
PMID- 27493989
TI - Effect of Aerobic Exercise Training on Blood Pressure in Indians: Systematic
Review.
AB - Introduction. High blood pressure (BP) is one of the most important modifiable
risk factors for cardiovascular diseases, which accounts for one in every eight
deaths worldwide. It has been predicted that, by 2020, there would be 111%
increase in cardiovascular deaths in India. Aerobic exercise in the form of brisk
walking, jogging, running, and cycling would result in reduction in BP. Many meta
analytical studies from western world confirm this. However, there is no such
review from Indian subcontinent. Objective. Our objective is to systematically
review and report the articles from India in aerobic exercise on blood pressure.
Methodology. Study was done in March 2016 in Google Scholar using search terms
"Aerobic exercise" AND "Training" AND "Blood pressure" AND "India." This search
produced 3210 titles. Results. 24 articles were identified for this review based
on inclusion and exclusion criteria. Total of 1107 subjects participated with
median of 25 subjects. Studies vary in duration from +3 weeks to 12 months with
each session lasting 15-60 minutes and frequency varies from 3 to 8 times/week.
The results suggest that there was mean reduction of -05.00 mmHg in SBP and
03.09 mmHg in DBP after aerobic training. Conclusion. Aerobic training reduces
the blood pressure in Indians.
PMID- 27493990
TI - Musculoskeletal Disorders and Perceived Work Demands among Female Nurses at a
Tertiary Care Hospital in India.
AB - Introduction. Musculoskeletal disorders (MSD) are common among nurses and can
affect patient outcomes. There is a dearth of literature on MSD among Indian
nurses. The study objective was to measure prevalence of MSD and their
association with perceived work demands and sociodemographic variables among
female nurses at a tertiary care hospital in rural India. Methods. A cross
sectional study was undertaken in 2013 through interviewer administered
questionnaires which comprised three parts: sociodemographic data, modified
Nordic questionnaire, and perceived physical and psychological work demands.
Results. 296 nurses with a mean age of 30.4 years participated. Prevalence of any
MSD in the last seven days was 60.5% with low back pain being the most common and
elbow pain the least common. Occurrence of any MSD was associated with age,
number of children, working hours at home, BMI, and total work experience. High
perceived physical demands score was associated with lower back (OR: 3.06) and
knee pain (OR: 7.73). Conclusion. Prevalence of MSD was high and occurrence of
lower back and knee MSD was associated with perceived physical demands. This
information should be used as a benchmark and guiding tool for designing work
place interventions to improve working conditions and health of nurses.
PMID- 27493991
TI - Microfluidic device for the formation of optically excitable, three-dimensional,
compartmentalized motor units.
AB - Motor units are the fundamental elements responsible for muscle movement. They
are formed by lower motor neurons and their muscle targets, synapsed via
neuromuscular junctions (NMJs). The loss of NMJs in neurodegenerative disorders
(such as amyotrophic lateral sclerosis or spinal muscle atrophy) or as a result
of traumatic injuries affects millions of lives each year. Developing in vitro
assays that closely recapitulate the physiology of neuromuscular tissues is
crucial to understand the formation and maturation of NMJs, as well as to help
unravel the mechanisms leading to their degeneration and repair. We present a
microfluidic platform designed to coculture myoblast-derived muscle strips and
motor neurons differentiated from mouse embryonic stem cells (ESCs) within a
three-dimensional (3D) hydrogel. The device geometry mimics the spinal cord-limb
physical separation by compartmentalizing the two cell types, which also
facilitates the observation of 3D neurite outgrowth and remote muscle
innervation. Moreover, the use of compliant pillars as anchors for muscle strips
provides a quantitative functional readout of force generation. Finally,
photosensitizing the ESC provides a pool of source cells that can be
differentiated into optically excitable motor neurons, allowing for
spatiodynamic, versatile, and noninvasive in vitro control of the motor units.
PMID- 27493993
TI - Shock compression response of forsterite above 250 GPa.
AB - Forsterite (Mg2SiO4) is one of the major planetary materials, and its behavior
under extreme conditions is important to understand the interior structure of
large planets, such as super-Earths, and large-scale planetary impact events.
Previous shock compression measurements of forsterite indicate that it may melt
below 200 GPa, but these measurements did not go beyond 200 GPa. We report the
shock response of forsterite above ~250 GPa, obtained using the laser shock wave
technique. We simultaneously measured the Hugoniot and temperature of shocked
forsterite and interpreted the results to suggest the following: (i) incongruent
crystallization of MgO at 271 to 285 GPa, (ii) phase transition of MgO at 285 to
344 GPa, and (iii) remelting above ~470 to 500 GPa. These exothermic and
endothermic reactions are seen to occur under extreme conditions of pressure and
temperature. They indicate complex structural and chemical changes in the system
MgO-SiO2 at extreme pressures and temperatures and will affect the way we
understand the interior processes of large rocky planets as well as material
transformation by impacts in the formation of planetary systems.
PMID- 27493995
TI - When lives are put on hold: Lengthy asylum processes decrease employment among
refugees.
AB - European governments are struggling with the biggest refugee crisis since World
War II, but there exists little evidence regarding how the management of the
asylum process affects the subsequent integration of refugees in the host
country. We provide new causal evidence about how one central policy parameter,
the length of time that refugees wait in limbo for a decision on their asylum
claim, affects their subsequent economic integration. Exploiting exogenous
variation in wait times and registry panel data covering refugees who applied in
Switzerland between 1994 and 2004, we find that one additional year of waiting
reduces the subsequent employment rate by 4 to 5 percentage points, a 16 to 23%
drop compared to the average rate. This deleterious effect is remarkably stable
across different subgroups of refugees stratified by gender, origin, age at
arrival, and assigned language region, a pattern consistent with the idea that
waiting in limbo dampens refugee employment through psychological discouragement,
rather than a skill atrophy mechanism. Overall, our results suggest that
marginally reducing the asylum waiting period can help reduce public expenditures
and unlock the economic potential of refugees by increasing employment among this
vulnerable population.
PMID- 27493992
TI - Analysis of neural crest-derived clones reveals novel aspects of facial
development.
AB - Cranial neural crest cells populate the future facial region and produce
ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle,
adipocytes, and many others. However, the contribution of individual neural crest
cells to certain facial locations and the general spatial clonal organization of
the ectomesenchyme have not been determined. We investigated how neural crest
cells give rise to clonally organized ectomesenchyme and how this early
ectomesenchyme behaves during the developmental processes that shape the face.
Using a combination of mouse and zebrafish models, we analyzed individual
migration, cell crowd movement, oriented cell division, clonal spatial
overlapping, and multilineage differentiation. The early face appears to be built
from multiple spatially defined overlapping ectomesenchymal clones. During early
face development, these clones remain oligopotent and generate various tissues in
a given location. By combining clonal analysis, computer simulations, mouse
mutants, and live imaging, we show that facial shaping results from an array of
local cellular activities in the ectomesenchyme. These activities mostly involve
oriented divisions and crowd movements of cells during morphogenetic events.
Cellular behavior that can be recognized as individual cell migration is very
limited and short-ranged and likely results from cellular mixing due to the
proliferation activity of the tissue. These cellular mechanisms resemble the
strategy behind limb bud morphogenesis, suggesting the possibility of common
principles and deep homology between facial and limb outgrowth.
PMID- 27493994
TI - Battery-free, stretchable optoelectronic systems for wireless optical
characterization of the skin.
AB - Recent advances in materials, mechanics, and electronic device design are rapidly
establishing the foundations for health monitoring technologies that have "skin
like" properties, with options in chronic (weeks) integration with the epidermis.
The resulting capabilities in physiological sensing greatly exceed those possible
with conventional hard electronic systems, such as those found in wrist-mounted
wearables, because of the intimate skin interface. However, most examples of such
emerging classes of devices require batteries and/or hard-wired connections to
enable operation. The work reported here introduces active optoelectronic systems
that function without batteries and in an entirely wireless mode, with examples
in thin, stretchable platforms designed for multiwavelength optical
characterization of the skin. Magnetic inductive coupling and near-field
communication (NFC) schemes deliver power to multicolored light-emitting diodes
and extract digital data from integrated photodetectors in ways that are
compatible with standard NFC-enabled platforms, such as smartphones and tablet
computers. Examples in the monitoring of heart rate and temporal dynamics of
arterial blood flow, in quantifying tissue oxygenation and ultraviolet dosimetry,
and in performing four-color spectroscopic evaluation of the skin demonstrate the
versatility of these concepts. The results have potential relevance in both
hospital care and at-home diagnostics.
PMID- 27493997
TI - Durable and sustained immune tolerance to ERT in Pompe disease with entrenched
immune responses.
AB - BACKGROUND: Enzyme replacement therapy (ERT) has prolonged survival and improved
clinical outcomes in patients with infantile Pompe disease (IPD), a rapidly
progressive neuromuscular disorder. Yet marked interindividual variability in
response to ERT, primarily attributable to the development of antibodies to ERT,
remains an ongoing challenge. Immune tolerance to ongoing ERT has yet to be
described in the setting of an entrenched immune response. METHODS: Three
infantile Pompe patients who developed high and sustained rhGAA IgG antibody
titers (HSAT) and received a bortezomib-based immune tolerance induction (ITI)
regimen were included in the study and were followed longitudinally to monitor
the long-term safety and efficacy. A trial to taper the ITI protocol was
attempted to monitor if true immune tolerance was achieved. RESULTS: Bortezomib
based ITI protocol was safely tolerated and led to a significant decline in rhGAA
antibody titers with concomitant sustained clinical improvement. Two of the 3 IPD
patients were successfully weaned off all ITI protocol medications and continue
to maintain low/no antibody titers. ITI protocol was significantly tapered in the
third IPD patient. B cell recovery was observed in all 3 IPD patients.
CONCLUSION: This is the first report to our knowledge on successful induction of
long-term immune tolerance in patients with IPD and HSAT refractory to agents
such as cyclophosphamide, rituximab, and methotrexate, based on an approach using
the proteasome inhibitor bortezomib. As immune responses limit the efficacy and
cost-effectiveness of therapy for many conditions, proteasome inhibitors may have
new therapeutic applications. FUNDING: This research was supported by a grant
from the Genzyme Corporation, a Sanofi Company (Cambridge, Massachusetts, USA),
and in part by the Lysosomal Disease Network, a part of NIH Rare Diseases
Clinical Research Network (RDCRN).
PMID- 27493998
TI - A location-centric network approach to analyzing epidemic dynamics.
AB - Recent health threats, such as the SARS, H1N1, and Ebola pandemics, have
stimulated great interest in network models to study the transmission of
communicable diseases through human interaction and mobility. Most current
network models have focused on an individual-centric perspective where
individuals are represented as nodes, and the interactions among them as edges.
Few of these models are concerned with the discovery of the spatial patterns and
dynamics of epidemics. We propose a location-centric, transmission network
approach, in which nodes denote locations and edges denote possible disease
transmissions between locations. We then identify the dynamics of transmission
flows, the dynamics of critical locations, and the spatial-temporal extent of
transmission pathways to assess the impact of these spatial dynamics on the
evolution of an epidemic. Results show that transmission flows shift from
elementary schools to middle schools and finally universities and professional
schools at different phases of an epidemic. Critical locations, identified using
network analysis, are responsible for the upsurge in transmission flows during
the peaks of the epidemic. The length of transmission pathways shows a power law
distribution and their spatial extent is rather small. Insights gained from this
study will help devise spatially sensitive strategies to control communicable
diseases.
PMID- 27493996
TI - Mechanized azobenzene-functionalized zirconium metal-organic framework for on
command cargo release.
AB - Stimuli-responsive metal-organic frameworks (MOFs) have gained increasing
attention recently for their potential applications in many areas. We report the
design and synthesis of a water-stable zirconium MOF (Zr-MOF) that bears
photoresponsive azobenzene groups. This particular MOF can be used as a reservoir
for storage of cargo in water, and the cargo-loaded MOF can be further capped to
construct a mechanized MOF through the binding of beta-cyclodextrin with the
azobenzene stalks on the MOF surface. The resulting mechanized MOF has shown on
command cargo release triggered by ultraviolet irradiation or addition of
competitive agents without premature release. This study represents a simple
approach to the construction of stimuli-responsive mechanized MOFs, and
considering mechanized UiO-68-azo made from biocompatible components, this smart
system may provide a unique MOF platform for on-command drug delivery in the
future.
PMID- 27493999
TI - Integration of Multi-Modal Biomedical Data to Predict Cancer Grade and Patient
Survival.
AB - The Big Data era in Biomedical research has resulted in large-cohort data
repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely
contain hundreds of matched patient samples for genomic, proteomic, imaging, and
clinical data modalities, enabling holistic and multi-modal integrative analysis
of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel
investigation of multi-modal data integration by combining histopathological
image and RNA-seq data. We compared the performances of two integrative
prediction methods: majority vote and stacked generalization. Results indicate
that integration of multiple data modalities improves prediction of cancer grade
and outcome. Specifically, stacked generalization, a method that integrates
multiple data modalities to produce a single prediction result, outperforms both
single-data-modality prediction and majority vote. Moreover, stacked
generalization reveals the contribution of each data modality (and specific
features within each data modality) to the final prediction result and may
provide biological insights to explain prediction performance.
PMID- 27494000
TI - [Perspectives to improve the sexual health of sexual and gender identity
minorities in Guatemala].
AB - Sexual and gender identity minorities in Guatemala are disproportionally affected
by HIV and other sexually transmitted infections (STI). However, little is known
about the health determinants among these minorities that contribute to infection
risk. Health researchers from the United States and Guatemala sought to explore
sexual health needs and identify characteristics of HIV/STI prevention programs
for these minorities.Our partnership conducted 8 focus groups with gay and
bisexual men, men who have sex with men, and transgender women; and 10 in-depth
interviews with community leaders. We analyzed transcripts of the focus groups
and in-depth interviews using constant comparison.We identified 24 factors that
influence sexual health which we organized into 5 ecological domains and 16
characteristics of potentially successful programs to reduce HIV/STI risk.The
identification of sexual risk factors and characteristics of potentially
successful programs offers great potential to develop interventions to help
reduce the risk of HIV/STI infection among these minorities in Guatemala.
PMID- 27494001
TI - Antifouling membranes for sustainable water purification: strategies and
mechanisms.
AB - One of the greatest challenges to the sustainability of modern society is an
inadequate supply of clean water. Due to its energy-saving and cost-effective
features, membrane technology has become an indispensable platform technology for
water purification, including seawater and brackish water desalination as well as
municipal or industrial wastewater treatment. However, membrane fouling, which
arises from the nonspecific interaction between membrane surface and foulants,
significantly impedes the efficient application of membrane technology. Preparing
antifouling membranes is a fundamental strategy to deal with pervasive fouling
problems from a variety of foulants. In recent years, major advancements have
been made in membrane preparation techniques and in elucidating the antifouling
mechanisms of membrane processes, including ultrafiltration, nanofiltration,
reverse osmosis and forward osmosis. This review will first introduce the major
foulants and the principal mechanisms of membrane fouling, and then highlight the
development, current status and future prospects of antifouling membranes,
including antifouling strategies, preparation techniques and practical
applications. In particular, the strategies and mechanisms for antifouling
membranes, including passive fouling resistance and fouling release, active off
surface and on-surface strategies, will be proposed and discussed extensively.
PMID- 27494002
TI - Gas-phase microsolvation of ubiquitin: investigation of crown ether complexation
sites using ion mobility-mass spectrometry.
AB - In this study the gas-phase structure of ubiquitin and its lysine-to-arginine
mutants was investigated using ion mobility-mass spectrometry (IM-MS) and
electron transfer dissociation-mass spectrometry (ETD-MS). Crown ether molecules
were attached to positive charge sites of the proteins and the resulting non
covalent complexes were analysed. Collision induced dissociation (CID)
experiments revealed relative energy differences between the wild type and the
mutant crown-ether complexes. ETD-MS experiments were performed to identify the
crown ether binding sites. Although not all of the binding sites could be
revealed, the data confirm that the first crown ether is able to bind to the N
terminus. IM-MS experiments show a more compact structure for specific charge
states of wild type ubiquitin when crown ethers are attached. However, data on
ubiquitin mutants reveal that only specific lysine residues contribute to the
effect of charge microsolvation. A compaction is only observed for one of the
investigated mutants, in which the lysine has no proximate interaction partner.
On the other hand when the lysine residues are involved in salt bridges,
attachment of crown ethers has little effect on the structure.
PMID- 27494003
TI - Kinetic trapping - a strategy for directing the self-assembly of unique
functional nanostructures.
AB - Supramolecular self-assembly into various nano- or microscopic structures based
on non-covalent interactions between molecules has been recognized as a very
efficient approach that leads to functional materials. Since most non-covalent
interactions are relatively weak and form and break without significant
activation barriers, the thermodynamic equilibrium of many supramolecular systems
can be easily influenced by processing pathways that allow the system to stay in
a kinetically trapped state. Thus far, kinetic traps have been found to be very
important in producing more elaborate structural and functional diversity of self
assembled systems. In this review, we try to summarize the approaches that can
produce kinetically trapped self-assemblies based on examples made by us. We
focus on the following subjects: (1) supramolecular pathway dependent self
assembly, including kinetically trapped self-assemblies facilitated by host-guest
chemistry, coordination chemistry, and electrostatic interactions; (2) physical
processing pathway dependent self-assembly, including solvent quality controlled
self-assembly, evaporation induced self-assembly and crystallization induced self
assembly.
PMID- 27494004
TI - Crystallinity-induced shape evolution of Pt-Ag nanosheets from branched
nanocrystals.
AB - Crystallinity offers countless opportunities for the controlled synthesis of
multimetallic 2D and 3D nanomaterials. Herein we have successfully synthesized 2D
Pt-Ag ultrathin nanosheets through the oxidative etching of twin seeds and 3D Pt
Ag-Cu tetrapods via altering the crystallinity through the incorporation of
copper into the Pt-Ag alloy. A better electrocatalytic activity is obtained for
the oxidation of formic acid which is 3.8 times higher than that of a commercial
platinum catalyst as the stepped surface atom densities are higher on the
nanosheets.
PMID- 27494005
TI - Studies of Energy-yielding Reactions in Thymus Nuclei : I. COMPARISON OF NUCLEAR
AND MITOCHONDRIAL PHOSPHORYLATION.
PMID- 27494006
TI - Studies on Energy-yielding Reactions in Thymus Nuclei : II. PATHWAYS OF AEROBIC
CARBOHYDRATE CATABOLISM.
PMID- 27494007
TI - Studies on Energy-yielding Reactions in Thymus Nuclei : III. PARTICIPATION OF
GLYCOLYSIS AND THE CITRIC ACID CYCLE IN NUCLEAR ADENOSINE TRIPHOSPHATE SYNTHESIS.
PMID- 27494008
TI - Conference presentations: Lead the poster parade.
PMID- 27494009
TI - Planned Home Vaginal Birth After Cesarean.
PMID- 27494010
TI - Diet Therapy May Be As Effective As Glyburide For Treatment Of Mild Gestational
Diabetes.
PMID- 27494011
TI - Early And Exclusive Breastfeeding May Protect Against Neonatal Mortality.
PMID- 27494012
TI - Provider Skill Influences Perinatal Outcomes.
PMID- 27494013
TI - Parents Desire Parenting Education During Prenatal Care.
PMID- 27494014
TI - THE NATURE OF DISCOVERY.
PMID- 27494015
TI - DEFINING A DISCOVERY: PRIORITY AND METHODOLOGICAL CONTROVERSY IN EARLY NINETEENTH
CENTURY ANATOMY.
AB - In the early nineteenth century, Charles Bell and Francois Magendie engaged in a
decades-long priority dispute over the discovery of the roots of motor and
sensory nerves. The constantly recalibrated arguments of its participants
illuminate changes in the life sciences during that period. When Bell first wrote
about the nerves in 1811, surgeon-anatomists ran small schools out of their
homes, natural theology was in vogue, exchanges between British and French
medical practitioners were limited by the Napoleonic Wars, and British
practitioners typically rejected experimental physiology and vivisection. By the
end of Magendie's career, medical science was produced in the laboratory, taught
through artfully produced performances of the sort at which Magendie excelled,
and disseminated through journals. It is not entirely clear which historical
character, Bell or Magendie, 'won' the dispute, nor that they even had clear and
consistent positions in it, but what is clear is that one style of science had
won out over the other, and over the course of the dispute, pedagogy lost pride
of place in medical science.
PMID- 27494016
TI - LEONARDO DA VINCI AND THE ORIGIN OF SEMEN.
AB - It is well known that Leonardo da Vinci made several drawings of the human male
anatomy. The early drawings (before 1500) were incorrect in identifying the
origin of semen, where he followed accepted teaching of his time. It is widely
thought that he did not correct this mistake, a view that is reflected in several
biographies. In fact, he made a later drawing (after 1500) in which the
description of the anatomy is remarkably accurate and must have been based on
careful dissection. In addition to highlighting this fact, acknowledged
previously in only one other source, this article reviews the background to
Leonardo's knowledge of the relevant anatomy.
PMID- 27494017
TI - Largest healthcare executive search firms.
PMID- 27494018
TI - Defining "intermittent UVR exposure".
AB - BACKGROUND: Cutaneous malignant melanoma (CMM) has been associated with
"intermittent UVR exposure", which in previous studies has mainly been assessed
by retrospective questionnaire data. Further, there is no uniform definition of
the term "intermittent UVR exposure". OBJECTIVES: We aimed to define and quantify
"intermittent UVR exposure" by an objective measure. METHODS: A broad study
population of adults and children had data collected during a summer period. Data
were personal UVR dosimetry measurements, from which the number of "intermittent
days" was derived, sun behaviour diaries and retrospective questionnaires. Two
definitions of intermittent UVR exposure were tested: (1) days when UVR dose
exceeded 3 times individual average daily UVR dose, and (2) days when UVR dose
exceeded individual constitutive skin type. Measures of nevi and lentigines were
used as surrogates for CMM. RESULTS: Using the first definition based solely on
UVR dosimetry data we found 1241 "intermittent days" out of a total of 17 277
days (7.2%) among 148 participants. The numbers for nevi and lentigo density were
significantly predicted by the number of intermittent days (R(2) = 0.15 and R(2)
= 0.40, p < 0.001). The corresponding numbers for prediction of nevi and lentigo
density by retrospective questionnaire data was lower (R(2) = 0.11, R(2) = 0.26,
p < 0.001). CONCLUSIONS: We introduce a well-defined objective measure of
intermittent UVR exposure. This measure may provide a better prediction of solar
skin damage and CMM than retrospective questionnaire data.
PMID- 27494019
TI - Hydrogen Peroxide Induced Cell Death: The Major Defences Relative Roles and
Consequences in E. coli.
AB - We recently developed a mathematical model for predicting reactive oxygen species
(ROS) concentration and macromolecules oxidation in vivo. We constructed such a
model using Escherichia coli as a model organism and a set of ordinary
differential equations. In order to evaluate the major defences relative roles
against hydrogen peroxide (H2 O2), we investigated the relative contributions of
the various reactions to the dynamic system and searched for approximate
analytical solutions for the explicit expression of changes in H2 O2 internal or
external concentrations. Although the key actors in cell defence are enzymes and
membrane, a detailed analysis shows that their involvement depends on the H2 O2
concentration level. Actually, the impact of the membrane upon the H2 O2 stress
felt by the cell is greater when micromolar H2 O2 is present (9-fold less H2 O2
in the cell than out of the cell) than when millimolar H2 O2 is present (about 2
fold less H2 O2 in the cell than out of the cell). The ratio between maximal
external H2 O2 and internal H2 O2 concentration also changes, reducing from 8 to
2 while external H2 O2 concentration increases from micromolar to millimolar.
This non-linear behaviour mainly occurs because of the switch in the predominant
scavenger from Ahp (Alkyl Hydroperoxide Reductase) to Cat (catalase). The
phenomenon changes the internal H2 O2 maximal concentration, which surprisingly
does not depend on cell density. The external H2 O2 half-life and the cumulative
internal H2 O2 exposure do depend upon cell density. Based on these analyses and
in order to introduce a concept of dose response relationship for H2 O2-induced
cell death, we developed the concepts of "maximal internal H2 O2 concentration"
and "cumulative internal H2 O2 concentration" (e.g. the total amount of H2 O2).
We predict that cumulative internal H2 O2 concentration is responsible for the H2
O2-mediated death of bacterial cells.
PMID- 27494020
TI - Reduction in Hospital-Wide Clinical Laboratory Specimen Identification Errors
following Process Interventions: A 10-Year Retrospective Observational Study.
AB - BACKGROUND: Accurate patient identification and specimen labeling at the time of
collection are crucial steps in the prevention of medical errors, thereby
improving patient safety. METHODS: All patient specimen identification errors
that occurred in the outpatient department (OPD), emergency department (ED), and
inpatient department (IPD) of a 3,800-bed academic medical center in Taiwan were
documented and analyzed retrospectively from 2005 to 2014. To reduce such errors,
the following series of strategies were implemented: a restrictive specimen
acceptance policy for the ED and IPD in 2006; a computer-assisted barcode
positive patient identification system for the ED and IPD in 2007 and 2010, and
automated sample labeling combined with electronic identification systems
introduced to the OPD in 2009. RESULTS: Of the 2000345 specimens collected in
2005, 1023 (0.0511%) were identified as having patient identification errors,
compared with 58 errors (0.0015%) among 3761238 specimens collected in 2014,
after serial interventions; this represents a 97% relative reduction. The total
number (rate) of institutional identification errors contributed from the ED,
IPD, and OPD over a 10-year period were 423 (0.1058%), 556 (0.0587%), and 44
(0.0067%) errors before the interventions, and 3 (0.0007%), 52 (0.0045%) and 3
(0.0001%) after interventions, representing relative 99%, 92% and 98% reductions,
respectively. CONCLUSIONS: Accurate patient identification is a challenge of
patient safety in different health settings. The data collected in our study
indicate that a restrictive specimen acceptance policy, computer-generated
positive identification systems, and interdisciplinary cooperation can
significantly reduce patient identification errors.
PMID- 27494021
TI - Relationship between Individual External Doses, Ambient Dose Rates and
Individuals' Activity-Patterns in Affected Areas in Fukushima following the
Fukushima Daiichi Nuclear Power Plant Accident.
AB - The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released
radioactive material into the atmosphere and contaminated the land in Fukushima
and several neighboring prefectures. Five years after the nuclear disaster, the
radiation levels have greatly decreased due to physical decay, weathering, and
decontamination operations in Fukushima. The populations of 12 communities were
forced to evacuate after the accident; as of March 2016, the evacuation order has
been lifted in only a limited area, and permanent habitation is still prohibited
in most of the areas. In order for the government to lift the evacuation order
and for individuals to return to their original residential areas, it is
important to assess current and future realistic individual external doses. Here,
we used personal dosimeters along with the Global Positioning System and
Geographic Information System to understand realistic individual external doses
and to relate individual external doses, ambient doses, and activity-patterns of
individuals in the affected areas in Fukushima. The results showed that the
additional individual external doses were well correlated to the additional
ambient doses based on the airborne monitoring survey. The results of linear
regression analysis suggested that the additional individual external doses were
on average about one-fifth that of the additional ambient doses. The reduction
factors, which are defined as the ratios of the additional individual external
doses to the additional ambient doses, were calculated to be on average 0.14 and
0.32 for time spent at home and outdoors, respectively. Analysis of the
contribution of various activity patterns to the total individual external dose
demonstrated good agreement with the average fraction of time spent daily in each
activity, but the contribution due to being outdoors varied widely. These results
are a valuable contribution to understanding realistic individual external doses
and the corresponding airborne monitoring-based ambient doses and time-activity
patterns of individuals. Moreover, the results provide important information for
predicting future cumulative doses after the return of residents to evacuation
order areas in Fukushima.
PMID- 27494022
TI - PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma
Exposed to Hydrogen Peroxide.
AB - Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) pathway has been
considered as major drug target site due to its frequent activation in cancer.
AKT regulates the activity of various targets to promote tumorigenesis and
metastasis. Accumulation of reactive oxygen species (ROS) has been linked to
oxidative stress and regulation of signaling pathways for metabolic adaptation of
tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS
source for oxidative stress preconditioning. Antioxidants are commonly considered
to be beneficial to reduce detrimental effects of ROS and are recommended as
dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary
component which has attracted much of interest due to its potential health
promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway
in H2O2 exposed Dalton's lymphoma ascite (DLA) cells. Further, regulation of PI3K
AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed.
Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and
resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and
AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as
TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 &
quercetin suppressed the enhanced level of ROS and significantly down-regulated
phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the
level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that
quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar
mechanism.
PMID- 27494023
TI - Stability of Chloropyromorphite in Ryegrass Rhizosphere as Affected by Root
Secreted Low Molecular Weight Organic Acids.
AB - Understanding the stability of chloropyromorphite (CPY) is of considerable
benefit for improving risk assessment and remediation strategies in contaminated
water and soil. The stability of CPY in the rhizosphere of phosphorus-deficient
ryegrass was evaluated to elucidate the role of root-secreted low molecular
weight organic acids (LMWOAs) on the dissolution of CPY. Results showed that CPY
treatments significantly reduced the ryegrass biomass and rhizosphere pH. The
presence of calcium nitrate extractable lead (Pb) and phosphorus (P) suggested
that CPY in the rhizosphere could be bioavailable, because P and Pb uptake by
ryegrass potentially provided a significant concentration gradient that would
promote CPY dissolution. Pb accumulation and translocation in ryegrass was found
to be significantly higher in P-sufficient conditions than in P-deficient
conditions. CPY treatments significantly enhanced root exudation of LMWOAs
irrigated with P-nutrient solution or P-free nutrient solution. Oxalic acid was
the dominant species in root-secreted LMWOAs of ryegrass under P-free nutrient
solution treatments, suggesting that root-secreted oxalic acid may be the driving
force of root-induced dissolution of CPY. Hence, our work, provides clarifying
hints on the role of LMWOAs in controlling the stability of CPY in the
rhizosphere.
PMID- 27494024
TI - Revised North Star Ambulatory Assessment for Young Boys with Duchenne Muscular
Dystrophy.
AB - The advent of therapeutic approaches for Duchenne muscular dystrophy (DMD) has
highlighted the need to identify reliable outcome measures for young boys with
DMD. The aim of this study was to develop a revised version of the North Star
Ambulatory Assessment (NSAA) suitable for boys between the age of 3 and 5 years
by identifying age appropriate items and revising the scoring system accordingly.
Using the scale in 171 controls between the age of 2.9 and 4.8 years, we
identified items that were appropriate at different age points. An item was
defined as age appropriate if it was completed, achieving a full score, by at
least 85% of the typically developing boys at that age. At 3 years (+/-3months)
there were only 8 items that were age appropriate, at 3 years and 6 months there
were 13 items while by the age of 4 years all 17 items were appropriate. A
revised version of the scale was developed with items ordered according to the
age when they could be reliably performed. The application of the revised version
of the scale to data collected in young DMD boys showed that very few of the DMD
boys were able to complete with a full score all the age appropriate items. In
conclusion, our study suggests that a revised version of the NSAA can be used in
boys from the age of 3 years to obtain information on how young DMD boys acquire
new abilities and how this correlates with their peers.
PMID- 27494025
TI - Strain Mediated Adaptation Is Key for Myosin Mechanochemistry: Discovering
General Rules for Motor Activity.
AB - A structure-based model of myosin motor is built in the same spirit of our early
work for kinesin-1 and Ncd towards physical understanding of its mechanochemical
cycle. We find a structural adaptation of the motor head domain in post
powerstroke state that signals faster ADP release from it compared to the same
from the motor head in the pre-powerstroke state. For dimeric myosin, an
additional forward strain on the trailing head, originating from the postponed
powerstroke state of the leading head in the waiting state of myosin, further
increases the rate of ADP release. This coordination between the two heads is the
essence of the processivity of the cycle. Our model provides a structural
description of the powerstroke step of the cycle as an allosteric transition of
the converter domain in response to the Pi release. Additionally, the variation
in structural elements peripheral to catalytic motor domain is the deciding
factor behind diverse directionalities of myosin motors (myosin V & VI). Finally,
we observe that there are general rules for functional molecular motors across
the different families. Allosteric structural adaptation of the catalytic motor
head in different nucleotide states is crucial for mechanochemistry. Strain
mediated coordination between motor heads is essential for processivity and the
variation of peripheral structural elements is essential for their diverse
functionalities.
PMID- 27494026
TI - Molecular Characterization of the ORF3 and S1 Genes of Porcine Epidemic Diarrhea
Virus Non S-INDEL Strains in Seven Regions of China, 2015.
AB - In an effort to trace the evolution of porcine epidemic diarrhea virus (PEDV), S1
and ORF3 genes of viruses identified in 41 pig farms from seven regions (North,
Northeast, Northwest, Central, East, South West, and South, respectively) of
China in 2015 were sequenced and analyzed. Sequence analysis revealed that the 41
ORF3 genes and 29 S1 genes identified in our study exhibited nucleotide
homologies of 98.2%-100% and 96.6%-100%, respectively; these two genes exhibited
low nucleotide sequence similarities with classical CV777 strain and early
Chinese strain LZC. Phylogenetic analysis indicated that the identified PEDV
strains belonged to global non S-INDEL strains, and exhibited genetic diversity;
S1 gene of the HLJ2015/DP1-1 strain harbored an unique deletion of 12 nucleotides
(A1130CAACTCCACTG1141); while the Chinese PEDV S-INDEL reference strains included
two types of the "CV777" S-INDEL as well as the "US" S-INDEL, and all co
circulated with Chinese non S-INDEL strains. Of 29 identified S1 genes, the SS2
epitope (Y748SNIGVCK755) was highly conserved, while the SS6 epitope
(L764QDGQVKI771) and pAPN receptor-binding region (aa 490-615) exhibited amino
substitutions. Nine possible recombination events were identified between the 29
identifed S1 genes and the 3 S1 reference genes from early Chinese PEDV strains.
The complete S genes of selected Chinese PEDV field strains (2011-2015) showed
5.18%-6.07% nucleotide divergence, which is far higher than the divergence
observed in early Chinese PEDV strains (3.1%) (P<0.05). Our data provide evidence
that PEDV non S-INDEL strains with genetic diversities and potential
recombination circulate in seven regions of China in 2015; Chinese PEDV S-INDEL
strains exhibit genetic diversity and co-circulate with non S-INDEL strains.
PMID- 27494027
TI - Dual Targeting of Intracellular Pathogenic Bacteria with a Cleavable Conjugate of
Kanamycin and an Antibacterial Cell-Penetrating Peptide.
AB - Bacterial infection caused by intracellular pathogens, such as Mycobacterium,
Salmonella, and Brucella, is a burgeoning global health epidemic that
necessitates urgent action. However, the therapeutic value of a number of
antibiotics, including aminoglycosides, against intracellular pathogenic bacteria
is compromised due to their inability to traverse eukaryotic membranes. For this
significant problem to be addressed, a cleavable conjugate of the antibiotic
kanamycin and a nonmembrane lytic, broad-spectrum antimicrobial peptide with
efficient mammalian cell penetration, P14LRR, was prepared. This approach allows
kanamycin to enter mammalian cells as a conjugate linked via a tether that breaks
down in the reducing environment within cells. Potent antimicrobial activity of
the P14KanS conjugate was demonstrated in vitro, and this reducible conjugate
effectively cleared intracellular pathogenic bacteria within macrophages more
potently than that of a conjugate lacking the disulfide moiety. Notably,
successful clearance of Mycobacterium tuberculosis within macrophages was
observed with the dual antibiotic conjugate, and Salmonella levels were
significantly reduced in an in vivo Caenorhabditis elegans model.
PMID- 27494028
TI - Integrated Monitoring of Mola mola Behaviour in Space and Time.
AB - Over the last decade, ocean sunfish movements have been monitored worldwide using
various satellite tracking methods. This study reports the near-real time
monitoring of fine-scale (< 10 m) behaviour of sunfish. The study was conducted
in southern Portugal in May 2014 and involved satellite tags and underwater and
surface robotic vehicles to measure both the movements and the contextual
environment of the fish. A total of four individuals were tracked using custom
made GPS satellite tags providing geolocation estimates of fine-scale resolution.
These accurate positions further informed sunfish areas of restricted search
(ARS), which were directly correlated to steep thermal frontal zones.
Simultaneously, and for two different occasions, an Autonomous Underwater Vehicle
(AUV) video-recorded the path of the tracked fish and detected buoyant particles
in the water column. Importantly, the densities of these particles were also
directly correlated to steep thermal gradients. Thus, both sunfish foraging
behaviour (ARS) and possibly prey densities, were found to be influenced by
analogous environmental conditions. In addition, the dynamic structure of the
water transited by the tracked individuals was described by a Lagrangian
modelling approach. The model informed the distribution of zooplankton in the
region, both horizontally and in the water column, and the resultant simulated
densities positively correlated with sunfish ARS behaviour estimator (rs = 0.184,
p<0.001). The model also revealed that tracked fish opportunistically displace
with respect to subsurface current flow. Thus, we show how physical forcing and
current structure provide a rationale for a predator's fine-scale behaviour
observed over a two weeks in May 2014.
PMID- 27494029
TI - Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and
Sufficient Driver Event for Renal Angiomyolipoma Development.
AB - Renal angiomyolipoma is a kidney tumor in the perivascular epithelioid (PEComa)
family that is common in patients with Tuberous Sclerosis Complex (TSC) and
Lymphangioleiomyomatosis (LAM) but occurs rarely sporadically. Though
histologically benign, renal angiomyolipoma can cause life-threatening hemorrhage
and kidney failure. Both angiomyolipoma and LAM have mutations in TSC2 or TSC1.
However, the frequency and contribution of other somatic events in tumor
development is unknown. We performed whole exome sequencing in 32 resected tumor
samples (n = 30 angiomyolipoma, n = 2 LAM) from 15 subjects, including three with
TSC. Two germline and 22 somatic inactivating mutations in TSC2 were identified,
and one germline TSC1 mutation. Twenty of 32 (62%) samples showed copy neutral
LOH (CN-LOH) in TSC2 or TSC1 with at least 8 different LOH regions, and 30 of 32
(94%) had biallelic loss of either TSC2 or TSC1. Whole exome sequencing
identified a median of 4 somatic non-synonymous coding region mutations (other
than in TSC2/TSC1), a mutation rate lower than nearly all other cancer types.
Three genes with mutations were known cancer associated genes (BAP1, ARHGAP35 and
SPEN), but they were mutated in a single sample each, and were missense variants
with uncertain functional effects. Analysis of sixteen angiomyolipomas from a TSC
subject showed both second hit point mutations and CN-LOH in TSC2, many of which
were distinct, indicating that they were of independent clonal origin. However,
three tumors had two shared mutations in addition to private somatic mutations,
suggesting a branching evolutionary pattern of tumor development following
initiating loss of TSC2. Our results indicate that TSC2 and less commonly TSC1
alterations are the primary essential driver event in angiomyolipoma/LAM, whereas
other somatic mutations are rare and likely do not contribute to tumor
development.
PMID- 27494031
TI - Genomic Inbreeding and Relatedness in Wild Panda Populations.
AB - Inbreeding and relatedness in wild panda populations are important parameters for
panda conservation. Habitat loss and fragmentation are expected to increase
inbreeding but the actual inbreeding levels in natural panda habitats were
unknown. Using 150,025 SNPs and 14,926 SNPs selected from published whole-genome
sequences, we estimated genomic inbreeding coefficients and relatedness of 49
pandas including 34 wild pandas sampled from six habitats. Qinling and Liangshan
pandas had the highest levels of inbreeding and relatedness measured by genomic
inbreeding and coancestry coefficients, whereas the inbreeding levels in Qionglai
and Minshan were 28-45% of those in Qinling and Liangshan. Genomic coancestry
coefficients between pandas from different habitats showed that panda populations
from the four largest habitats, Minshan, Qionglai, Qinling and Liangshan, were
genetically unrelated. Pandas between these four habitats on average shared 66.0
69.1% common alleles and 45.6-48.6% common genotypes, whereas pandas within each
habitat shared 71.8-77.0% common alleles and 51.7-60.4% common genotypes. Pandas
in the smaller populations of Qinling and Liangshan were more similarly to each
other than pandas in the larger populations of Qionglai and Minshan according to
three genomic similarity measures. Panda genetic differentiation between these
habitats was positively related to their geographical distances. Most pandas
separated by 200 kilometers or more shared no common ancestral alleles. The
results provided a genomic quantification of the actual levels of inbreeding and
relatedness among pandas in their natural habitats, provided genomic confirmation
of the relationship between genetic diversity and geographical distances, and
provided genomic evidence to the urgency of habitat protection.
PMID- 27494030
TI - Innovative Approaches Using Lichen Enriched Media to Improve Isolation and
Culturability of Lichen Associated Bacteria.
AB - Lichens, self-supporting mutualistic associations between a fungal partner and
one or more photosynthetic partners, also harbor non-photosynthetic bacteria. The
diversity and contribution of these bacteria to the functioning of lichen
symbiosis have recently begun to be studied, often by culture-independent
techniques due to difficulties in their isolation and culture. However, culturing
as yet unculturable lichenic bacteria is critical to unravel their potential
functional roles in lichen symbiogenesis, to explore and exploit their
biotechnological potential and for the description of new taxa. Our objective was
to improve the recovery of lichen associated bacteria by developing novel
isolation and culture approaches, initially using the lichen Pseudevernia
furfuracea. We evaluated the effect of newly developed media enriched with novel
lichen extracts, as well as the influence of thalli washing time and different
disinfection and processing protocols of thalli. The developed methodology
included: i) the use of lichen enriched media to mimic lichen nutrients,
supplemented with the fungicide natamycin; ii) an extended washing of thalli to
increase the recovery of ectolichenic bacteria, thus allowing the disinfection of
thalli to be discarded, hence enhancing endolichenic bacteria recovery; and iii)
the use of an antioxidant buffer to prevent or reduce oxidative stress during
thalli disruption. The optimized methodology allowed significant increases in the
number and diversity of culturable bacteria associated with P. furfuracea, and it
was also successfully applied to the lichens Ramalina farinacea and Parmotrema
pseudotinctorum. Furthermore, we provide, for the first time, data on the
abundance of culturable ecto- and endolichenic bacteria that naturally colonize
P. furfuracea, R. farinacea and P. pseudotinctorum, some of which were only able
to grow on lichen enriched media. This innovative methodology is also applicable
to other microorganisms inhabiting these and other lichen species.
PMID- 27494032
TI - Putative Mechanisms of Viral Transmission and Molecular Dysregulation of Mammary
Epithelial Cells by Human Papillomavirus: Implications for Breast Cancer.
AB - Breast cancer is the most common cancer in women worldwide. Several studies have
demonstrated the presence of Human papillomavirus (HPV) DNA in breast cancer
samples. However, the role of HPV in breast carcinogenesis is not clear, and the
interaction mechanisms between this infectious agent and the breast cancer cell
need to be more fully clarified. In this article, we discuss the putative roles
of HPV infection in breast carcinogenesis.
PMID- 27494033
TI - Inactivation of Pseudomonas aeruginosa by chitosan coated iron oxide
nanoparticles.
AB - BACKGROUND: Pseudomonas aeruginosa is one of the potent opportunistic pathogens
associated with respiratory and urinary tract infection. The bacterium owes its
pathogenicity due to the intrinsic resistance to antibiotics and disinfectants.
OBJECTIVE: The present study is focused on the synthesis of antibacterial
chitosan coated iron oxide nanoparticles for rapid inactivation of Pseudomonas
aeruginosa. We have discussed the relevant patents on synthesis and antibacterial
potential of metallic nanoparticles and chitosan. METHOD: Chitosan coated iron
oxide nanoparticles were synthesized by co-precipitation method at room
temperature using non-toxic chitosan and iron salts in alkali media. The
particles were characterized and evaluated for antibacterial property against
Pseudomonas aeruginosa. RESULTS: The average size of the particles was measured
as 52 nm. The surface area of the coated particles was as high as 90 +/-5 m2/g.
FTIR spectra confirmed the coating of chitosan on nanoparticles. The coated
particles showed excellent antibacterial activity against the bacteria. The
minimum inhibitory concentration of the coated particles was 105 ug mol-1. The
morphological alteration and cytoplasmic leakage of bacteria were confirmed by
SEM image and release of intracellular constituents, respectively. Higher 260 nm
absorbance value confirmed stronger antibacterial activity of the coated
nanoparticles as compared to pure chitosan and bare iron oxide nanoparticles.
CONCLUSION: The study indicated that chitosan coated iron oxide nanoparticles
have superior antibacterial property as compared to pure chitosan and iron oxide
nanoparticles.
PMID- 27494034
TI - The Year's Best: Interpersonal Elements of Bisexual Women's Most Satisfying
Sexual Experiences in the Past Year.
AB - Sexual satisfaction is commonly defined and discussed in physiological terms of
arousal and orgasm. Yet this narrow discourse does not accommodate the complex,
multidimensional, and interpersonal aspects of sexual experience. To broaden and
deepen our understanding of sexual satisfaction, we employed McClelland's (2014)
holistic four-factor framework of sexual satisfaction in a theoretical thematic
analysis of 39 behaviorally bisexual women's descriptions of their "best"
partnered sexual experiences from the past year. We found women's accounts mapped
on to four elements: emotional attunement, emotional gratification, partner
gratification, and sensory gratification. Relational and emotional dynamics,
including emotional security, quality of interpersonal interaction during and
after a sexual encounter, mutuality, intimacy, partner skill, novelty, and
communication, were key to participants' best sex experiences. Our findings
support a multifaceted model of women's sexual satisfaction that accounts for
emotional, relational, and embodied experiences and the diverse relationships and
behaviors these might involve.
PMID- 27494035
TI - Correction to "What is in a Beer? Proteomic Characterization and Relative
Quantification of Hordein (Gluten) in Beer".
PMID- 27494036
TI - Long-term update of the 24954 EORTC phase III trial on larynx preservation.
AB - The long-term results of the EORTC 24954 trial comparing sequential versus
alternating chemotherapy and radiotherapy (RT) for patients with locally advanced
laryngeal and hypopharyngeal cancer are reported. From 1996 to 2004, 450 patients
were randomly assigned (1-1) to a sequential arm (SA = induction cisplatin
5fluorouracil followed by a 70Gy-RT for the responders or a total laryngectomy
and post-operative RT for the non-responders) and an alternating arm (AA =
cisplatin-5fluorouracil alternated with three 2-week courses of 20 Gy-RT for a
total dose of 60 Gy). Median follow-up was 10.2 years. Ten-year survival with
functional larynx (primary end-point) and overall survival were similar in both
arms (18.7% and 33.6% in SA versus 18.3% and 31.6% in AA). Late toxicity was also
similar; however, a trend for higher larynx preservation and better laryngeal
function was observed in AA.
PMID- 27494039
TI - Synthesis, Characterization and Biological Activities of Creatinine Amides and
Creatinine Schiff Bases.
AB - BACKGROUND: In spite of substantial progress in scientific cognizance and medical
technology, still infectious diseases are among the leading cause of morbidity
and mortality. Creatinine and Schiff bases are well known for their diverse range
of biological activities and thought to be emerging and useful therapeutic target
for the treatment of several diseases. METHODS: The present work was aimed to
illustrate the influence of substitution of amides and Schiff bases on creatinine
and their antimicrobial, antioxidant and anti-urease effectiveness was
determined. Creatinine substituted amides (1-2) and creatinine Schiff bases (3-7)
were synthesized and characterized by NMR and IR spectral data in combination
with elemental analysis. All the compounds (1-7) were investigated on Jack bean
urease for their urease inhibitory potential. Investigation of antimicrobial
activity of the compounds was made by the agar dilution method. Moreover, 1,1
diphenyl-2- picrylhydrazyl (DPPH) method was used to determine their antioxidant
potential. Molecular docking studies were also carried out to elucidate their
relationship with the binding pockets of the enzyme. RESULTS: The compounds were
found to be potent inhibitors of urease. The synthesized derivatives exhibited
significant inhibition against Gram-positive and Gram-negative bacterial strains,
as compared to standard, ciprofloxacin. Creatinine based derivatives exhibited
potential antifungal activity when tested on infectious and pathogenic fungal
strains. Similarly, most of the compounds exhibited good antioxidant activity.
CONCLUSION: These derivatives may serve as a source of potential antioxidants and
also help to retard microbial growth in food industry. Similarly, the studies
provide a basis for further research to develop more potent urease inhibitory
compounds of medicinal /agricultural interest.
PMID- 27494037
TI - Methadone is superior to fentanyl in treating neuropathic pain in patients with
head-and-neck cancer.
AB - BACKGROUND: Cancer pain is still inadequately treated in up to 60% of cancer
patients. Based on the additional effect on the N-Methyl-d-Aspartate receptor, we
expected that methadone (Met) could provide better pain relief than fentanyl
(Fen) in cancer pain with a neuropathic pain component. METHODS: A randomised
controlled trial was performed with 52 strong opioids naive patients with head
and-neck cancer with substantial pain (pain Numerical Rating Scale [NRS] > 4) and
a neuropathic pain component (Douleur Neuropathique [DN4] > 4). Twenty-six
patients were treated with Met and 26 with Fen. Patients were evaluated at 1, 3
and 5 weeks. The primary outcomes were reduction in average pain, clinical
success (defined as 50% average pain decrease) and reduction in pain
interference. Secondary outcomes were global perceived effect (GPE) and side
effects. FINDINGS: Reduction in NRS was higher with the use of Met at 1, 3 and 5
weeks (pain change 2.9, 3.1 and 3.1) compared to Fen (1.4, 1.7 and 2.0). This
difference was significant at 1 (p = 0.011) and at 3 weeks (p = 0.03). Clinical
success (>50% improvement) was higher with Met at 1 week (15% versus 50%, p =
0.012). The change in pain interference, the GPE and side-effect profile were not
significantly different between the groups. INTERPRETATION: This is the first
study to compare the effects of Met to Fen in cancer patients with a neuropathic
pain component. Based on the results of this study, Met should be considered in
the treatment of oncological pain with a neuropathic component.
PMID- 27494040
TI - Injury pattern in lethal motorbikes-pedestrian collisions, in the area of
Barcelona, Spain.
AB - INTRODUCTION: There are several studies about M1 type vehicle-pedestrian
collision injury pattern, and based on them, there has been several changes in
automobiles for pedestrian protection. However, the lack of sufficient studies
about injury pattern in motorbikes-pedestrian collisions leads to a lack of
optimization design of these vehicles. The objective of this research is to study
the injury pattern of pedestrians involved in collisions with motorized two
wheeled vehicles. METHODS: A retrospective descriptive study of pedestrian's
deaths after collisions with motorcycles in an urban area, like Barcelona was
performed. The cases were collected from the Forensic Pathology Service database
of the Institute of Legal Medicine of Catalonia. The selected cases were
categorized as pedestrian-motorcycle collision, between January 1st, 2005 and
December 31st, 2014. Data were collected from the autopsy, medical, and police
report. The collected information was then analyzed using Microsoft Excel
statistical functions. RESULTS: Traumatic Brain Injury is the main cause of death
in pedestrian hit by motorized two-wheeled vehicles (62.85%). The most frequent
injury was the subarachnoid hemorrhage, in 71.4% of cases, followed by cerebral
contusions and skull base fractures (65.7%). By contrast, pelvic fractures and
tibia fractures only appeared in 28.6%. CONCLUSIONS: The study characterizes the
injury pattern of pedestrians involved in a collision with motorized two-wheeled
vehicles in an urban area, like Barcelona, which has been found to be different
from other vehicle-pedestrian collisions, with a higher incidence of brain
injuries and minor frequency of lower extremities fractures in pelvis, tibia and
fibula.
PMID- 27494041
TI - Reducing Phosphorus to Curb Lake Eutrophication is a Success.
AB - As human populations increase and land-use intensifies, toxic and unsightly
nuisance blooms of algae are becoming larger and more frequent in freshwater
lakes. In most cases, the blooms are predominantly blue-green algae
(Cyanobacteria), which are favored by low ratios of nitrogen to phosphorus. In
the past half century, aquatic scientists have devoted much effort to
understanding the causes of such blooms and how they can be prevented or reduced.
Here we review the evidence, finding that numerous long-term studies of lake
ecosystems in Europe and North America show that controlling algal blooms and
other symptoms of eutrophication depends on reducing inputs of a single nutrient:
phosphorus. In contrast, small-scale experiments of short duration, where
nutrients are added rather than removed, often give spurious and confusing
results that bear little relevance to solving the problem of cyanobacteria blooms
in lakes.
PMID- 27494042
TI - Exercise improves depressive symptoms in older adults: An umbrella review of
systematic reviews and meta-analyses.
AB - Late-life depression is a growing public health concern. Exercise may be of added
value but the literature remains equivocal. We conducted a systematic overview of
meta-analyses and an exploratory pooled analysis of previous meta-analyses to
determine the effect of exercise on depression in older adults. Two independent
researchers searched Pubmed, CINAHL, Cochrane Plus, PsycArticles, and PsycInfo
for meta-analyses on exercise in late-life depression. Methodological quality was
assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument.
We pooled effect sizes from previous meta-analyses of randomized controlled
trials to determine the effect of exercise on depression in older adults. The
systematic review yielded 3 meta-analyses. In total, 16 unique cohorts of 1487
participants were included. The quality of the three included meta-analyses was
considered as "moderate" according to AMSTAR scores. No serious adverse events
were reported. Compared to controls (n=583), those exercising (n=541)
significantly reduced depressive symptoms. Our umbrella review indicates that
exercise is safe and efficacious in reducing depressive symptoms in older people.
Since exercise has many other known health benefits, it should be considered as a
core intervention in the multidisciplinary treatment of older adults experiencing
depression.
PMID- 27494043
TI - Drugs for Hepatitis.
PMID- 27494044
TI - "Race for the Surface": Eukaryotic Cells Can Win.
AB - With an aging population and the consequent increasing use of medical implants,
managing the possible infections arising from implant surgery remains a global
challenge. Here, we demonstrate for the first time that a precise nanotopology
provides an effective intervention in bacterial cocolonization enabling the
proliferation of eukaryotic cells on a substratum surface, preinfected by both
live Gram-negative, Pseudomonas aeruginosa, and Gram-positive, Staphylococcus
aureus, pathogenic bacteria. The topology of the model black silicon (bSi)
substratum not only favors the proliferation of eukaryotic cells but is
biocompatible, not triggering an inflammatory response in the host. The
attachment behavior and development of filopodia when COS-7 fibroblast cells are
placed in contact with the bSi surface are demonstrated in the dynamic study,
which is based on the use of real-time sequential confocal imaging. Bactericidal
nanotopology may enhance the prospect for further development of inherently
responsive antibacterial nanomaterials for bionic applications such as
prosthetics and implants.
PMID- 27494045
TI - Development and application of dot-enzyme-linked immunosorbent (dot-ELISA) assay
for detection of Brucella melitensis and evaluation of the shedding pattern in
infected goats.
AB - Early and accurate diagnosis of Brucella melitensis is essential for the
treatment and control of brucellosis both in animals and humans. The thrust for
the development of a rapid diagnostic technique to overcome the limitations of
conventional microbiological and serological tests brought about this
investigation on the development and application of dot-ELISA for antigen and
antibody detection in infected goats. Fifteen apparently healthy Boer aged 2-3
years which tested negative for brucellosis using PCR and ELISA, were grouped
into A (10 goats infected intraocularly with 107 CFU of B. melitensis) and B (5
goats) as control. Discharges (ocular, nasal, and vaginal) and blood were
collected at days 3, 7, 10, 14, weekly until 42 post-infection (pi) for dot
ELISA, PCR, and RBPT. Dot-ELISA detected B. melitensis antigen and antibody in
group A at day 3 and 7 pi, respectively with adequate sensitivity and specificity
relative to PCR and RBPT. The bacteria shedding detected from discharges at day 3
pi in the nasal and ocular route with dot-ELISA. Group B were consistently
negative. Values such as speed, simplicity, field adaptability, high sensitivity,
and specificity make dot-ELISA a rapid and adequate technique for diagnosis of
brucellosis in B. melitensis infected goats within few hours.
PMID- 27494046
TI - Dissecting the Influence of Protein Flexibility on the Location and Thermodynamic
Profile of Explicit Water Molecules in Protein-Ligand Binding.
AB - Explicit water molecules in the binding site of proteins play a crucial role for
protein-ligand association. Recent advances in computer-aided drug discovery
methodology allow for an accurate prediction of the localized position and
thermodynamic profile of water molecules (i.e., hydration sites) in the binding
site. The underlying calculations are based on MD simulations of explicit water
molecules in a restrained protein structure. However, the ligand-binding process
is typically associated with protein conformational change that influences the
position and thermodynamic properties of the hydration site. In this manuscript,
we present the developments of two methods to incorporate the influence of
protein conformational change on hydration sites either by following the
conformational transition step-by-step (method I) or to match the hydration sites
of the two transition end states using local coordinate systems (method II).
Using these methods, we highlight the difference in the estimated protein
desolvation free energy with and without inclusion of protein flexibility. To the
best of our knowledge, this is the first study that explicitly studies the
influence of protein conformational change on the position and thermodynamic
profiles of water molecules and provides methodology to incorporate protein
flexibility into the estimation of the desolvation free energy.
PMID- 27494048
TI - Examining the durability of incidentally learned trust from gaze cues.
AB - In everyday interactions we find our attention follows the eye gaze of faces
around us. As this cueing is so powerful and difficult to inhibit, gaze can
therefore be used to facilitate or disrupt visual processing of the environment,
and when we experience this we infer information about the trustworthiness of the
cueing face. However, to date no studies have investigated how long these
impressions last. To explore this we used a gaze-cueing paradigm where faces
consistently demonstrated either valid or invalid cueing behaviours. Previous
experiments show that valid faces are subsequently rated as more trustworthy than
invalid faces. We replicate this effect (Experiment 1) and then include a brief
interference task in Experiment 2 between gaze cueing and trustworthiness rating,
which weakens but does not completely eliminate the effect. In Experiment 3, we
explore whether greater familiarity with the faces improves the durability of
trust learning and find that the effect is more resilient with familiar faces.
Finally, in Experiment 4, we push this further and show that evidence of trust
learning can be seen up to an hour after cueing has ended. Taken together, our
results suggest that incidentally learned trust can be durable, especially for
faces that deceive.
PMID- 27494047
TI - Engineering of New Pneumocandin Side-Chain Analogues from Glarea lozoyensis by
Mutasynthesis and Evaluation of Their Antifungal Activity.
AB - Pneumocandins are lipohexapeptides of the echinocandin family that inhibit fungal
1,3-beta-glucan synthase. Most of the pathway steps have been identified
previously. However, the lipoinitiation reaction has not yet been experimentally
verified. Herein, we investigate the lipoinitiation step of pneumocandin
biosynthesis in Glarea lozoyensis and demonstrate that the gene product,
GLligase, catalyzes this step. Disruption of GLHYD, a gene encoding a putative
type II thioesterase and sitting upstream of the pneumocandin acyl side chain
synthase gene, GLPKS4, revealed that GLHYD was necessary for optimal function of
GLPKS4 and to attain normal levels of pneumocandin production. Double disruption
of GLHYD and GLPKS4 did not affect residual function of the GLligase or GLNRPS4.
Mutasynthesis experiments with a gene disruption mutant of GLPKS4 afforded us an
opportunity to test the substrate specificity of GLligase in the absence of its
native polyketide side chain to diversify pneumocandins with substituted side
chains. Feeding alternative side chain precursors yielded acrophiarin and four
new pneumocandin congeners with straight C14, C15, and C16 side chains. A
comprehensive biological evaluation showed that one compound, pneumocandin I (5),
has elevated antifungal activity and similar hemolytic activity compared to
pneumocandin B0, the starting molecule for caspofungin. This study demonstrates
that the lipoinitiation mechanism in pneumocandin biosynthesis involves
interaction among a highly reducing PKS, a putative type II thioesterase, and an
acyl AMP-ligase. A comparison of the SAR among pneumocandins with different
length acyl side chains demonstrated the potential for using GLligase for future
engineering of new echinocandin analogues.
PMID- 27494049
TI - Computational profiling of pore properties of outer membrane proteins.
PMID- 27494050
TI - Examination of Pyridazine as a Possible Scaffold for Nucleophilic Catalysis.
AB - Pyridazines with amino groups positioned para to each aromatic ring nitrogen and
fixed in six-membered rings were prepared. The representative symmetric amino N
Et derivative was found to slightly exceed DMAP in catalytic activity in the
acetylation reaction of a tertiary alcohol in C6D6. Nucleophilicity eclipsing
that of DMAP was established in competitive reactions using phenacyl bromide as
the electrophile, and the unsymmetric N-Et derivative was revealed to have even
higher nucleophilicity.
PMID- 27494051
TI - Co-Occurring Disorders: A Challenge for Mexican Community-Based Residential Care
Facilities for Substance Use.
AB - OBJECTIVE: In Mexico, specialized treatment services for people with co-occurring
disorders are limited within public health services, while private options are
deemed too costly. More than 2,000 community-based residential care facilities
have risen as an alternative and are the main source of treatment for individuals
with substance use disorders; however, suboptimal practices within such
facilities are common. Information on the clinical characteristics of patients
receiving care in these facilities is scarce and capacity to provide high-quality
care for co-occurring disorders is unknown. The aims of this study were to
examine the prevalence of co-occurring disorders in patients receiving treatment
for substance use in these community-based residential centers and to assess
whether the presence of co-occurring disorders is associated with higher severity
of substance use, psychiatric symptomatology, and other health risks. METHODS:
This study was conducted with 601 patients receiving treatment for substance use
disorders at 30 facilities located in five Mexican states, recruited in 2013 and
2014. Patients were assessed with self-report measures on substance use, service
utilization, suicidality, HIV risk behaviors, psychiatric symptomatology, and
psychiatric disorder diagnostic criteria. RESULTS: The prevalence of any co
occurring disorder in this sample was 62.6%. Antisocial personality disorder was
the most prevalent (43.8%), followed by major depressive disorder (30.9%). The
presence of a co-occurring disorder was associated with higher severity of
psychiatric symptoms (aB = .496, SE = .050, p < .05); more days of substance use
(aB = .219, SE = .019, p < .05); current suicidal ideation (aOR = 5.07, 95% CI
[2.58, 11.17]; p < .05), plans (aOR = 5.17 95% CI [2.44, 12.73]; p < .05), and
attempts (aOR = 6.43 95% CI [1.83, 40.78]; p < .05); more sexual risk behaviors;
and more contact with professional services (aOR = 1.77, 95% CI [1.26, 2.49], p <
.05). CONCLUSIONS: Co-occurring disorders are highly prevalent in community-based
residential centers in Mexico and are associated with significantly increased
probability of other health risks. This highlights the need to develop care
standards for this population and the importance of clinical research in these
settings.
PMID- 27494052
TI - Effects of Group-Based Exercise on Range of Motion, Muscle Strength, Functional
Ability, and Pain During the Acute Phase After Total Knee Arthroplasty: A
Controlled Clinical Trial.
AB - Study Design Prospective observational study including a historical control
group. Background The extent to which group-based exercise (G-EXE) improves knee
range of motion (ROM), quadriceps strength, and gait ability is similar to that
of individualized exercise (I-EXE) at 6 weeks and 8 months after total knee
arthroplasty (TKA). However, the benefits of G-EXE for patients during the acute
recovery phase after TKA remain unclear. Objective To determine the effects of G
EXE during the acute recovery phase after TKA on knee ROM, quadriceps strength,
functional ability, and knee pain. Methods Two hundred thirty-one patients
participated in G-EXE in addition to regular ambulation and activities-of-daily
living exercises twice daily during the hospital stay. Outcomes were compared to
those of a retrospectively identified, historical control group (I-EXE group [n =
206]) that included patients who performed exercises identical to those performed
by the G-EXE group. The outcomes included knee ROM, quadriceps strength, pain
intensity, and timed up-and-go test score at 1 month before surgery and at
discharge. Analyses were adjusted for age, body mass index, sex, length of
hospital stay, and preoperative values. Results Changes in ROM of knee flexion
and extension (P<.001) and quadriceps strength (P<.001) were significantly better
in the G-EXE group than those in the I-EXE group at discharge. The pain intensity
improved more in the G-EXE group than in the I-EXE group at discharge (P<.001).
However, the changes in the timed up-and-go scores were not significantly
different. Conclusion Patients performing G-EXE in addition to regular ambulation
and activities-of-daily-living exercises demonstrated greater changes in knee
ROM, quadriceps strength, and knee pain than those performing I-EXE in addition
to regular ambulation and activities-of-daily-living exercises. The
nonrandomized, asynchronous design decreases certainty of these findings. Level
of Evidence Therapy, level 2b. J Orthop Sports Phys Ther 2016;46(9):742-748. Epub
5 Aug 2016. doi:10.2519/jospt.2016.6409.
PMID- 27494053
TI - Comparison of Electromyographic Activity of the Superior and Inferior Portions of
the Gluteus Maximus Muscle During Common Therapeutic Exercises.
AB - Study Design Controlled laboratory study, repeated-measures design. Background
Previous studies have reported that the superior and inferior portions of the
gluteus maximus have different functional roles. Knowledge of how the different
portions of the gluteus maximus are activated during therapeutic exercise may
lead to more specific exercise prescription. Objective To compare muscle
activation of the superior and inferior portions of the gluteus maximus during
commonly used therapeutic exercises. Methods Twenty healthy persons participated.
Electromyographic (EMG) signals were obtained from the superior and inferior
portions of the gluteus maximus using fine-wire electrodes. Normalized EMG signal
amplitudes were compared between the superior and inferior gluteus maximus across
11 exercises using a 2-way repeated-measures analysis of variance. Results The
superior portion of the gluteus maximus had significantly greater relative EMG
activity than the inferior portion of the gluteus maximus during exercises that
incorporated elements of hip abduction and/or external rotation (5 of 11
exercises evaluated). There was no significant difference in activation between
the superior and inferior portions of the gluteus maximus during the remaining 6
exercises. Conclusion The results of the present study demonstrate preferential
activation of the superior portion of the gluteus maximus during exercises that
incorporate elements of hip abduction and/or external rotation. In contrast,
exercises that primarily involve hip extension target both portions of the
gluteus maximus to a similar extent. J Orthop Sports Phys Ther 2016;46(9):794
799. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6493.
PMID- 27494054
TI - The Influence of a Prefabricated Foot Orthosis on Lower Extremity Mechanics
During Running in Individuals With Varying Dynamic Foot Motion.
AB - Study Design Controlled laboratory study, cross-sectional. Background Orthotic
prescription is often based on the premise that the mechanical effects will be
more prominent in individuals with greater calcaneal eversion. Objective To
compare the effects of a prefabricated foot orthosis on lower extremity
kinematics and kinetics between recreational athletes with high and low calcaneal
eversion during running. Methods Thirty-one recreational athletes were included
in this study. Three-dimensional kinematic and kinetic data were collected while
running with and without a foot orthosis. Participants were grouped based on the
degree of calcaneal eversion during the running trials relative to a standing
trial (dynamic foot motion). The effects of the orthosis on the frontal and
transverse plane angles and moments of the hip and knee were compared between the
10 participants with the greatest and least amount of dynamic foot motion.
Results There were no significant interactions (group by orthotic condition) for
any of the kinematic or kinetic variables of interest. Conclusion The effects of
an orthosis on the mechanics of the hip and knee do not appear to be dependent on
an individual's dynamic foot motion. J Orthop Sports Phys Ther 2016;46(9):749
755. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6253.
PMID- 27494055
TI - Sensitivity to Change of a Computer Adaptive Testing Instrument for Outcome
Measurement After Hip and Knee Arthroplasty and Periacetabular Osteotomy.
AB - Study Design Clinical measurement study. Background Computer adaptive testing
(CAT) methods may allow detection of change across the continuum of
osteoarthritis (OA) care. Objective To evaluate the sensitivity to change of a
self-report OA CAT instrument (OA-CAT) following surgery. Methods Core measures
consisted of the 5-item OA-CAT function, pain, and disability scales; the Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the University of
California at Los Angeles activity rating scale; and the Medical Outcomes Study
12-Item Short-Form Health Survey (SF-12), which were administered in 3 samples.
Fifty-three patients with hip dysplasia completed the core measures, the Hip
disability and Osteoarthritis Outcome Score physical function short form (HOOS
PS), and the Modified Harris Hip Score (MHHS) before periacetabular osteotomy,
and at 6 months, 1 year, and 2 years after periacetabular osteotomy. The hip (n =
62) and knee (n = 66) arthroplasty samples completed core measures and the MHHS
or the Knee Society's Knee Scoring System at baseline and at 3-month follow-up.
Mean change, floor and ceiling effects (percent), and effect size were
calculated. Results For osteotomy, the 6-month physical function effect sizes for
the OA-CAT, WOMAC, HOOS-PS, MHHS, and SF-12 physical component summary scores
were 0.66 (95% confidence interval [CI]: 0.08, 1.61), 0.78 (95% CI: 0.56, 1.10),
0.91 (95% CI: 0.70, 1.21), 0.64 (95% CI: 0.22, 1.07), and 0.87 (95% CI: 0.53,
1.38), respectively. Effect-size trends were all increased at 1 year, and most
were level at 2 years. For hip arthroplasty, the OA-CAT, WOMAC, MHHS, and SF-12
effect sizes were 1.27 (95% CI: 0.88, 1.84), 1.50 (95% CI: 1.20, 1.80), 0.68 (95%
CI: 0.35, 1.04), and 0.56 (95% CI: 0.29, 0.88), respectively. For knee
arthroplasty, the OA-CAT, WOMAC, Knee Society Knee Scoring System, and SF-12
effect sizes were 0.81 (95% CI: 0.56, 1.14), 0.85 (95% CI: 0.61, 1.10), 0.09 (95%
CI: -0.22, 0.40), and -0.01 (95% CI: -0.39, 0.31), respectively. The OA-CAT and
SF-12 demonstrated smaller ceiling effects than the HOOS-PS and other
instruments, especially at 1 and 2 years. Administration time was less for the OA
CAT than for the WOMAC physical function subscale. Conclusion The OA-CAT shows
potential for outcome measurement after hip and knee surgery. Larger studies are
needed to better understand relative performance. J Orthop Sports Phys Ther
2016;46(9):756-767. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6442.
PMID- 27494056
TI - Test-Retest Reliability of Rating of Perceived Exertion and Agreement With 1
Repetition Maximum in Adults.
AB - Study Design Clinical measurement. Background It has been suggested that rating
of perceived exertion (RPE) may be a useful alternative to 1-repetition maximum
(1RM) to determine proper resistance exercise dosage. However, the test-retest
reliability of RPE for resistance exercise has not been determined. Additionally,
prior research regarding the relationship between 1RM and RPE is conflicting.
Objectives The purpose of this study was to (1) determine test-retest reliability
of RPE related to resistance exercise and (2) assess agreement between
percentages of 1RM and RPE during quadriceps resistance exercise. Methods A
sample of participants with and without knee pathology completed a series of knee
extension exercises and rated the perceived difficulty of each exercise on a 0-to
10 RPE scale, then repeated the procedure 1 to 2 weeks later for test-retest
reliability. To determine agreement between RPE and 1RM, participants completed
knee extension exercises at various percentages of their 1RM (10% to 130% of
predicted 1RM) and rated the perceived difficulty of each exercise on a 0-to-10
RPE scale. Percent agreement was calculated between the 1RM and RPE at each
resistance interval. Results The intraclass correlation coefficient indicated
excellent test-retest reliability of RPE for quadriceps resistance exercises
(intraclass correlation coefficient = 0.895; 95% confidence interval: 0.866,
0.918). Overall percent agreement between RPE and 1RM was 60%, but agreement was
poor within the ranges that would typically be used for training (50% 1RM for
muscle endurance, 70% 1RM and greater for strength). Conclusion Test-retest
reliability of perceived exertion during quadriceps resistance exercise was
excellent. However, agreement between the RPE and 1RM was poor, especially in
common training zones for knee extensor strengthening. J Orthop Sports Phys Ther
2016;46(9):768-774. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6498.
PMID- 27494057
TI - Feedback and Feedforward Control During Walking in Individuals With Chronic Ankle
Instability.
AB - Study Design Controlled laboratory study. Background Recurrent ankle sprains
associated with chronic ankle instability (CAI) occur not only in challenging
sports but also in daily walking. Understanding whether and how CAI alters
feedback and feedforward controls during walking may be important for developing
interventions for CAI prevention or treatment. Objective To understand whether
CAI is associated with changes in feedback and feedforward control when
individuals with CAI are subjected to experimental perturbation during walking.
Methods Twelve subjects with CAI and 12 control subjects walked on a treadmill
while adapting to external loading that generated inversion perturbation at the
ankle joint. Ankle kinematics around heel contact during and after the adaptation
were compared between the 2 groups. Results Both healthy and CAI groups showed an
increase in eversion around heel contact in early adaptation to the external
loading. However, the CAI group adapted back toward the baseline, while the
healthy controls showed further increase in eversion in late adaptation. When the
external loading was removed in the postadaptation period, healthy controls
showed an aftereffect consisting of an increase in eversion around heel contact,
but the CAI group showed no aftereffect. Conclusion The results provide
preliminary evidence that CAI may alter individuals' feedback and feedforward
control during walking. J Orthop Sports Phys Ther 2016;46(9):775-783. Epub 5 Aug
2016. doi:10.2519/jospt.2016.6403.
PMID- 27494058
TI - Differential Diagnosis and Intervention of Proximal Median Nerve Entrapment: A
Resident's Case Problem.
AB - Study Design Resident's case problem. Background Entrapment neuropathies
represent a diagnostic challenge and require a comprehensive understanding of the
nerve's path and the anatomical structures that may cause compression of the
nerve. This resident's case problem details the evaluation and differential
diagnosis process for median nerve entrapment resulting from forceful and
repetitive pronation/supination motions. Diagnosis Median nerve compression
syndromes include pronator syndrome, anterior interosseous nerve syndrome, and
carpal tunnel syndrome. A cluster of clinical special tests were performed to
determine the anatomical site of median nerve entrapment. Based on the patient's
history and clinical test results, a diagnosis of pronator syndrome was
determined. Provocation testing specific to pronator syndrome assisted with
further localizing the site of entrapment to the pronator teres muscle, which
guided effective management strategies. Discussion This resident's case problem
illustrates the importance of detailed anatomical knowledge and a differential
diagnostic process when evaluating a patient with signs and symptoms of an
entrapment neuropathy of the median nerve. Electrodiagnostic studies are useful
in ruling out carpal tunnel and anterior interosseous nerve syndromes, but are
often inconclusive in cases of pronator syndrome. Therefore, a diagnosis of
pronator syndrome in this case problem was based on a detailed understanding of
median nerve anatomy, potential sites of compression, and unique clinical
features associated with this condition. Level of Evidence Differential
diagnosis, level 4. J Orthop Sports Phys Ther 2016;46(9):800-808. Epub 5 Aug
2016. doi:10.2519/jospt.2016.6723.
PMID- 27494062
TI - Blood-Brain Barrier ABC-transporter P-glycoprotein in Alzheimer's Disease:
Still a Suspect?
AB - Alzheimer's disease is a neurodegenerative disorder and the most common form of
dementia. One of the pathological hallmarks of the disease is amyloid deposition
in the brain. The major cause of amyloid deposition in sporadic Alzheimer's
disease is thought to be decreased brain clearance of amyloid. There is
compelling preclinical evidence that the blood-brain barrier, a structure that
maintains homeostasis in the central nervous system and protects the brain from
harmful substances, plays an important role in amyloid clearance. Indeed, several
dedicated transporter systems are present at the blood-brain barrier which may
have a role in brain amyloid clearance, such as P-glycoprotein (P-gp). In vitro
experiments and animal studies indicated increased amyloid deposition when P-gp
was eliminated by pharmacological blockade or by genetic modification. And as
decreased P-gp expression has been found in AD brains, P-gp became more and more
a suspect. Using an imaging technique called positron emission tomography, P-gp
transporter function was found to be decreased in Alzheimer's disease patients
compared to healthy controls, further establishing the important role of P-gp in
the pathogenesis of the disease. In this review, we summarize what is now known
about P-gp in Alzheimer's disease pathology, as these transporters may provide a
novel target for therapeutic strategies.
PMID- 27494060
TI - Tuberculosis-induced Fish-Scale Degeneration of the Central Airways.
PMID- 27494063
TI - Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier
with Positron Emission Tomography.
AB - P-glycoprotein function is associated with a number of neurodegenerative and
psychiatric diseases as well as with pharmacoresistance to for example
antiepileptic drugs. The ability to measure P-gp function in vivo would allow for
an increased understanding of the mechanisms of disease and treatment. This
review assesses the various approaches to in vivo quantification of P-gp function
using currently available P-gp tracers and PET in humans. First, the use of
compartment models, and their interpretation in terms of P-gp function at the
blood-brain barrier, is discussed. Then, the methods that have been used to
quantify PET data of the P-gp tracers [11C]verapamil, [11C]N-desmetyl-loperamide
(dLop), [11C]laniquidar, [11C]phenytoin, [11C]tariquidar and [11C]elacridar are
reviewed. In summary, the extraction of P-gp substrate PET tracers, which is
their plasma to tissue rate constant K corrected for variations in regional
cerebral blood flow, is generally considered to be the preferred measure of P-gp
function.
PMID- 27494059
TI - Maternal Calorie Restriction Causing Uteroplacental Insufficiency Differentially
Affects Mammalian Placental Glucose and Leucine Transport Molecular Mechanisms.
AB - We examined the effect of mild (Mi; ~25%) and moderate (Mo; ~50%) maternal
calorie restriction (MCR) vs ad libitum-fed controls on placental glucose and
leucine transport impacting fetal growth potential. We observed in MiMCR a
compensatory increase in transplacental (TP) glucose transport due to increased
placental glucose transporter isoform (GLUT)-3 but no change in GLUT1 protein
concentrations. This change was paralleled by increased glut3 mRNA and 5
hydroxymethylated cytosines with enhanced recruitment of histone 3 lysine
demethylase to the glut3 gene locus. To assess the biologic relevance of
placental GLUT1, we also examined glut1 heterozygous null vs wild-type mice and
observed no difference in placental GLUT3 and TP or intraplacental glucose and
leucine transport. Both MCR states led to a graded decrease in TP and
intraplacental leucine transport, with a decline in placental L amino acid
transporter isoform 2 (LAT2) concentrations and increased microRNA-149 (targets
LAT2) and microRNA-122 (targets GLUT3) expression in MoMCR alone. These changes
were accompanied by a step-wise reduction in uterine and umbilical artery Doppler
blood flow with decreased fetal left ventricular ejection fraction and fractional
shortening. We conclude that MiMCR transactivates placental GLUT3 toward
preserving TP glucose transport in the face of reduced leucine transport. This
contrasts MoMCR in which a reduction in placental GLUT3 mediated glucose
transport with a reciprocal increase in miR-122 expression was encountered. A
posttranscriptional reduction in LAT2-mediated leucine transport also occurred
with enhanced miR-149 expression. Both MCR states, although not affecting
placental GLUT1, resulted in uteroplacental insufficiency and fetal growth
restriction with compromised cardiovascular health.
PMID- 27494064
TI - Non-ambient Conditions in the Investigation and Manufacturing of Drug Forms.
AB - For the formation of a drug, a pharmacologically active compound must be prepared
in a specific form. The drug must be manufactured, packaged, stored, transported,
administred and delivered to a target in the body. To successfully prepare a drug
form that will be robust through manufacturing, stable before administration and
active with high bioavailability after administration, one needs to produce solid
forms with controlled crystal structure and particle size and shape - often as
multi-component composites. Considering drugs as materials, one can apply the
knowledge of solid-state chemistry and materials science and non-ambient
conditions to obtain solid forms with optimized properties. These conditions
include, among others, different types of mechanical and ultrasonic treatment,
hydrostatic compression, high-temperature or cryogenic spray-drying and
crystallization from supercritical solvents. Solid-state reactions (e.g.
dehydration or clathrate decomposition) can be effective in accessing metastable
polymorphs or in micronizing a sample uniformly. To achieve control over the drug
forms and the processes used for their robust manufacturing, one needs to take
into account both the thermodynamic and kinetic aspects of their transformations.
PMID- 27494065
TI - Importance of P-gp PET Imaging in Pharmacology.
AB - Capillary endothelial cells in the brain express P-glycoprotein (P-gp), which
works as a functional blood-brain barrier (BBB). P-gp pumps out multiple types of
molecules from the brain parenchyma into the blood. Therefore, altered P-gp
function at the BBB will change the concentrations of therapeutic drugs in the
central nervous system (CNS) and hence impact the toxicity and efficacy of CNS
drugs. Positron emission tomography (PET) is the only way to non-invasively
measure P-gp function in the living human brain. PET imaging of P-gp function was
first demonstrated in 1998 with the substrate tracer racemic [11C]verapamil.
Since then, several drug interaction studies and proof-of-concept studies
regarding drug resistance have been performed with P-gp PET imaging. Although
preclinical findings have been very positive regarding the possibilities and
importance of P-gp PET imaging, very few studies have shown the clinical
relevance of P-gp PET imaging in different disorders of the brain. This review
summarizes the pharmacological studies with PET using substrate tracers and
emphasizes the importance of PET imaging to understand the mechanism of action of
CNS drugs.
PMID- 27494066
TI - Experimental-Theoretic Approach to Drug-Lymphocyte Interactome Networks with Flow
Cytometry and Spectral Moments Perturbation Theory.
AB - We can combine experimental techniques like Flow Cytometry Analysis (FCA) with
Chemoinformatics methods to predict the complex networks of interactions between
organic compounds and targets in the immune system. In this work, we determined
experimentally the values of EC50 = 17.82 MUg/mL and Cytotoxicity = 20.6 % for
the anti-microbial / anti-parasite drug Dermofural over Balb/C CD9 lymphocytes
using flow cytometry. After that, we developed a new Perturbation-theory model
for Drug-Cell Target Interactome in Lymphocytes based on dispersion-polarization
moments of drug structure. The models correctly classifies 34591 out of 42715
(Accuracy = 80.9%) cases of perturbations in assay endpoints of 11492 drugs
(including both train and validation series). Each endpoint correspond to one out
of 2616 assays, 38 molecular and cellular targets, 77 standard type measures, in
four possible (human and rodents).
PMID- 27494067
TI - Detection of Quinolone Resistance in Salmonella typhimurium Pig Isolates
Determined by gyrA Gene Mutation Using PCR- and Sequence-Based Techniques within
the gyrA Gene.
AB - BACKGROUND: The emergence of reduced susceptibility to fluoroquinolones among
Salmonella enterica serotype Typhimurium isolates leading to clinical failure of
treatment poses a great therapeutic challenge. METHODS: The current study is
focused on the evaluation of the minimum inhibitory concentration (MIC) of
quinolones in 29 Salmonella typhimurium of 86 Salmonella spp. strains, obtained
from pigs from the State of Mexico. The MIC was performed with the Kirby-Bauer
method. On the other hand, the GyrA gene was sequenced. The present study was
undertaken to describe the resistance profiles and fluoroquinolone resistance
mechanism of Salmonella Typhimurium. RESULTS: The DNA sequence of the gyrA genes
from Salmonella enterica serovar typhimurium revealed strong similarity between
gyrA and its counterpart in Escherichia coli. The sequencing of quinolone
resistance-determining region (QRDR) of the gyrA gene showed the presence of
mutation at either S83 or at D87 in almost all the Salmonella typhimurium
isolates. CONCLUSION: This mutation, although phenotypically expressed as
decreased susceptibility to fluoroquinolones goes undetected by the disk
diffusion method using the present method of Kirby-Bauer. Hence, it can increase
morbidity and mortality due to delay in appropriate antibiotic treatment.
PMID- 27494068
TI - Down-regulation of 21A Alu RNA as a tool to boost proliferation maintaining the
tissue regeneration potential of progenitor cells.
AB - 21A is an Alu non-coding (nc) RNA transcribed by RNA polymerase (pol) III. While
investigating the biological role of 21A ncRNA we documented an inverse
correlation between its expression level and the rate of cell proliferation. The
downregulation of this ncRNA not only caused a boost in cell proliferation, but
was also associated to a transient cell dedifferentiation, suggesting a possible
involvement of this RNA in cell dedifferentiation/reprogramming. In this study,
we explored the possibility to enhance proliferation and dedifferentiation of
cells of interest, by 21A down-regulation, using a mixture of chemically modified
Anti-21A RNAs. Our results confirmed the validity of this approach that allows
the amplification of specific cell populations, in a controlled manner and
without inducing permanent effects. In addition to induce cell proliferation, the
procedure did not decrease the tissue regeneration potential of progenitor cells
in two different cell systems.
PMID- 27494069
TI - In vitro influence of light radiation on hair steroid concentrations.
AB - Hair cortisol concentrations (hairF) are considered to be relatively robust to
various confounding influences. However, a potentially important covariate factor
that has received little attention in this context is hair exposure to
ultraviolet/sunlight radiation. We conducted a detailed experimental
investigation to examine the effects of light exposure on hair cortisol. In study
I, a hydrocortisone-containing solution was subjected to short-term artificial
light irradiation for 1, 3, 5, 10, 15, or 30min to evaluate the stability of
cortisol molecules due to radiant energy. In study II, hair samples (N=12) were
subjected to single short-term artificial light irradiation for 0, 1, or 5h to
examine light-induced effects in the hair matrix. In study III, hair samples
(N=25) were subjected to long-term naturalistic sunlight radiation over a period
of two months (during summer) with daily exposure times of 0, 1, 3, or 6h,
respectively. Besides cortisol, studies II & III also examined concentrations of
cortisone (hairE), dehydroepiandrosterone (hairDHEA) and progesterone (hairP) in
hair, quantified using LC-MS/MS technology. Results across the three studies
consistently revealed effects of light irradiation on hair steroid
concentrations: Longer light exposure resulted in a decrease of dissolved
hydrocortisone (study I) as well as of hairF and hairE (studies II and III).
Conversely, hairDHEA and hairP increased with longer natural sunlight exposure
times (study III), while this effect was not observed for short-term artificial
light irradiation (study II). Combined, our findings imply sunlight exposure as a
potential confound in hair steroid research. Given the experimental character of
this investigation, the magnitude of this effect under real-life testing
conditions is difficult to estimate. To support future investigation into this,
we designed a 'sunlight-exposure' questionnaire to share with the research
community. The assessment and statistical accounting for sunlight exposure
related effects in future hair steroid research (using this or a similar
questionnaire) may help to reduce the potential influence of this unwanted error
source and could thus lead to more valid and reliable results. In addition, our
data strongly suggest that hair samples for steroid analyses need to be stored in
a dark environment.
PMID- 27494070
TI - Stress-induced release of matrix metalloproteinase-9 in patients with coronary
artery disease: The possible influence of cortisol.
AB - Stress and inflammation are both important risk factors for coronary artery
disease (CAD). However, the susceptibility to stress-induced inflammation and its
determinants have been little explored in patients with CAD. Here, our aim was to
study the stress-induced inflammatory response, more precisely the early release
of matrix metalloproteinase (MMP)-9, and its association with cortisol response
in patients with CAD. Sixty-four patients underwent a standardized laboratory
stress test. The stress-induced release of MMP-9 was closely associated with the
release of other neutrophil-associated proteins, MMP-8 and myeloperoxidase (MPO).
It also showed a large variation among patients, as did cortisol. Twenty minutes
after stress, a negative association between changes in MMP-9 and cortisol was
seen (p<0.01). In vitro, dexamethasone reduced the IL-8-mediated release of MMP-9
from neutrophils, indicating that glucocorticoids may exert rapid effects on
neutrophil activation. Further characterization of patients revealed that stress
induced release of MMP-9 was related to leukocyte telomere shortening and
increased ultrasound-assessed plaque occurrence in the carotid arteries, but not
to other characteristics such as age, gender or psychological background factors.
The susceptibility to stress-induced release of MMP-9 may thus have impact on
disease phenotype. Stress tests can be useful to identify CAD patients in need of
novel prevention and treatment strategies.
PMID- 27494072
TI - Anti-adipogenic effect of Glycoside St-E2 and Glycoside St-C1 isolated from the
leaves of Acanthopanax henryi (Oliv.) Harms in 3T3-L1 cells.
AB - Acanthopanax henryi (Oliv.) Harms has been used in the treatment of arthritis,
rheumatism, and abdominal pain. This study evaluated whether natural compounds
isolated from the leaves of A. henryi (Oliv.) Harms could inhibit adipocyte
differentiation by regulating transcriptional factors such as peroxisome
proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding
protein alpha (C/EBPalpha). AMP-activated protein kinase (AMPK) activity was also
evaluated. Among the several compounds isolated from the leaves of A. henryi
(Oliv.) Harms, Glycoside St-C1 and Glycoside St-E2 significantly decreased lipid
accumulation and the expressions of PPARgamma and C/EBPalpha. Glycoside St-C1 and
Glycoside St-E2 were found to activate AMPK when they regulated PPARgamma and
C/EBPalpha. Results confirmed that Glycoside St-C1 and Glycoside St-E2 isolated
from the leaves of A. henryi (Oliv.) Harms can inhibit adipogenesis through the
AMPK-PPARgamma-C/EBPalpha mechanism. Thus, this study suggests that Glycoside St
C1 and Glycoside St-E2 have a therapeutic effect due to activation of the
AMPKalpha.
PMID- 27494071
TI - Concurrent and prospective associations between HPA axis activity and depression
symptoms in newlywed women.
AB - We investigated the extent to which individual differences in activity of the
hypothalamic pituitary adrenal axis (HPA) are associated with depressive symptoms
among newlywed couples. Participants were 218 couples (M age 28.4 years; 94%
White) who provided 5 saliva samples (later assayed for cortisol and DHEA-S)
before and after participation in a discussion of a major area of disagreement in
their relationship. Depressive symptoms were assessed initially, and
approximately 19- and 37-months later. Results revealed an interactive effect
suggesting that concordant levels of cortisol and DHEA-S (either both high or
both low) were concurrently and prospectively associated with higher depression
scores. Interestingly, this interactive effect was observed for wives only - not
for husbands. These observations underscore contemporary theoretical assumptions
that the expression of the association between HPA activity and depression is
dependent on factors related to the interaction between characteristics of the
person and features of the social environment, and moderated by co-occurring
variation in endocrine milieu.
PMID- 27494073
TI - Predicting permeability of regular tissue engineering scaffolds: scaling analysis
of pore architecture, scaffold length, and fluid flow rate effects.
AB - The main aim of this research is to numerically obtain the permeability
coefficient in the cylindrical scaffolds. For this purpose, a mathematical
analysis was performed to derive an equation for desired porosity in terms of
morphological parameters. Then, the considered cylindrical geometries were
modeled and the permeability coefficient was calculated according to the velocity
and pressure drop values based on the Darcy's law. In order to validate the
accuracy of the present numerical solution, the obtained permeability coefficient
was compared with the published experimental data. It was observed that this
model can predict permeability with the utmost accuracy. Then, the effect of
geometrical parameters including porosity, scaffold pore structure, unit cell
size, and length of the scaffolds as well as entrance mass flow rate on the
permeability of porous structures was studied. Furthermore, a parametric study
with scaling laws analysis of sample length and mass flow rate effects on the
permeability showed good fit to the obtained data. It can be concluded that the
sensitivity of permeability is more noticeable at higher porosities. The present
approach can be used to characterize and optimize the scaffold microstructure due
to the necessity of cell growth and transferring considerations.
PMID- 27494074
TI - Executive dysfunction and survival in patients with amyotrophic lateral
sclerosis: Preliminary report from a Serbian centre for motor neuron disease.
AB - Our objective was to determine whether the presence of executive dysfunction in
non-demented amyotrophic lateral sclerosis (ALS) patients might affect the
longevity of survival. Forty-eight consecutive non-demented ALS patients (mean
age = 52.93 +/- 12.37) were followed for five years. All patients underwent
clinical and neuropsychological assessments at baseline visit. Further, a yearly
follow-up check for associated dementia (ALS-Dem) was completed and the time of
death was recorded, when applicable. Executive deficits were shown in 49.5% of
ALS patients, with the most striking differences found on the tests of verbal
fluency (both phonemic and category, p < 0.01); as well as inefficient strategy
on a working memory test (p < 0.05); as on the more demanding levels of the
planning and problem solving task (p < 0.01). It appears that the baseline
executive status might predict survival in ALS (p = 0.075), and the patients
presenting executive dysfunction could have up to three times greater risk of
death, after adjustment by several potential confounding factors. In conclusion,
this study suggests that executive dysfunction could potentially influence
survival in ALS patients. The cognitive testing might give us important clues
about the prognosis of the disease. Further studies with larger sample size are
necessary.
PMID- 27494075
TI - D-dimer test for excluding the diagnosis of pulmonary embolism.
AB - BACKGROUND: Pulmonary embolism (PE) can occur when a thrombus (blood clot)
travels through the veins and lodges in the arteries of the lungs, producing an
obstruction. People who are thought to be at risk include those with cancer,
people who have had a recent surgical procedure or have experienced long periods
of immobilisation and women who are pregnant. The clinical presentation can vary,
but unexplained respiratory symptoms such as difficulty breathing, chest pain and
an increased respiratory rate are common.D-dimers are fragments of protein
released into the circulation when a blood clot breaks down as a result of normal
body processes or with use of prescribed fibrinolytic medication. The D-dimer
test is a laboratory assay currently used to rule out the presence of high D
dimer plasma levels and, by association, venous thromboembolism (VTE). D-dimer
tests are rapid, simple and inexpensive and can prevent the high costs associated
with expensive diagnostic tests. OBJECTIVES: To investigate the ability of the D
dimer test to rule out a diagnosis of acute PE in patients treated in hospital
outpatient and accident and emergency (A&E) settings who have had a pre-test
probability (PTP) of PE determined according to a clinical prediction rule (CPR),
by estimating the accuracy of the test according to estimates of sensitivity and
specificity. The review focuses on those patients who are not already established
on anticoagulation at the time of study recruitment. SEARCH METHODS: We searched
13 databases from conception until December 2013. We cross-checked the reference
lists of relevant studies. SELECTION CRITERIA: Two review authors independently
applied exclusion criteria to full papers and resolved disagreements by
discussion.We included cross-sectional studies of D-dimer in which
ventilation/perfusion (V/Q) scintigraphy, computerised tomography pulmonary
angiography (CTPA), selective pulmonary angiography and magnetic resonance
pulmonary angiography (MRPA) were used as the reference standard.* PARTICIPANTS:
Adults who were managed in hospital outpatient and A&E settings and were
suspected of acute PE were eligible for inclusion in the review if they had
received a pre-test probability score based on a CPR.* INDEX TESTS: quantitative,
semi quantitative and qualitative D-dimer tests.* Target condition: acute
symptomatic PE.* Reference standards: We included studies that used pulmonary
angiography, V/Q scintigraphy, CTPA and MRPA as reference standard tests. DATA
COLLECTION AND ANALYSIS: Two review authors independently extracted data and
assessed quality using Quality Assessment of Diagnostic Accuracy Studies-2
(QUADAS-2). We resolved disagreements by discussion. Review authors extracted
patient-level data when available to populate 2 * 2 contingency tables (true
positives (TPs), true-negatives (TNs), false-positives (FPs) and false-negatives
(FNs)). MAIN RESULTS: We included four studies in the review (n = 1585 patients).
None of the studies were at high risk of bias in any of the QUADAS-2 domains, but
some uncertainty surrounded the validity of studies in some domains for which the
risk of bias was uncertain. D-dimer assays demonstrated high sensitivity in all
four studies, but with high levels of false-positive results, especially among
those over the age of 65 years. Estimates of sensitivity ranged from 80% to 100%,
and estimates of specificity from 23% to 63%. AUTHORS' CONCLUSIONS: A negative D
dimer test is valuable in ruling out PE in patients who present to the A&E
setting with a low PTP. Evidence from one study suggests that this test may have
less utility in older populations, but no empirical evidence was available to
support an increase in the diagnostic threshold of interpretation of D-dimer
results for those over the age of 65 years.
PMID- 27494076
TI - Pro- and anti-angiogenic VEGF mRNAs in autoimmune thyroid diseases.
AB - The aim of this study was to assess the relationships between five different
splice isoforms of VEGF mRNA and its plasma levels in individuals treated for
autoimmune thyroid diseases (AITD); mainly Graves' disease (GD) and Hashimoto's
thyroiditis (HT). In a population from Tunisia, levels of thyroid hormones and
antibodies were quantified simultaneously with plasma VEGF and VEGF mRNA isoforms
after a period of 6 months of patients' treatment. Plasma VEGF was measured in
110 AITD patients (21 GD and 89 HT patients). VEGF isoforms (VEGF121, VEGF165,
VEGF145 and VEGF189 pro-angiogenic isoforms and VEGF165b anti-angiogenic isoform)
in peripheral blood mononuclear cells were quantified in 71 patients (20 GD and
51 HT patients) and 86 healthy controls. Decreased levels of VEGF189 mRNA were
observed in AITD compared to controls. VEGF165 was increased in GD patients
compared to controls and the VEGF165b was increased in HT patients compared to
GD. We observed increased levels of VEGF165b in hypothyroid AITD patients after
treatment. We have also shown that the VEGF145 isoform levels were determined by
FT4 in all patients and by the thyroid status after 6 months of treatment only in
HT patients. An association was observed for VEGF165 mRNA levels with anti-TPO
antibodies in all patients. Finally, FT4 was associated with VEGF plasma levels
but only in healthy controls. In conclusion, this descriptive study highlights
the specificity of VEGF mRNA isoforms in AITD, a fact underlining the need for
novel clinical trials and the development of personalised theranostic approaches.
PMID- 27494078
TI - d-Amino Acid Scan of Two Small Proteins.
AB - A "D-scan" of two small proteins, the disulfide-rich Ecballium elaterium trypsin
inhibitor II (EETI-II) and a minimized Z domain of protein A (Z33), is reported.
For each protein, the stereochemistry of one amino acid at a time was inverted to
generate a series of diastereomers. In much the same way an alanine scan
determines necessary residues for protein function, the D-scan elucidated the
critical stereocenters of the 30-residue EETI-II and the 33-residue Z33. The
folding properties and activity of each variant were investigated. A total of 24
out of 30 EETI-II D-scan analogues folded to give a three-disulfide product. Of
the 24 variants that folded, half were high-affinity trypsin inhibitors, and
three were as active as the wild type (WT). Of these 12 active variants, most
were substantially less stable to reduction than WT EETI-II (WT first reduction
potential -270.0 +/- 1.5 mV, WT second reduction potential -307.2 +/- 1.1 mV).
Similarly, ten Z33 analogues retained high binding affinity to IgG (KD < 250 nM,
WT: 24 +/- 1 nM) and 12 additional analogues had reduced but appreciable IgG
binding affinity (KD between 250 nM and 2.5 MUM). As with EETI-II, most Z33
analogues were substantially less stable than the WT (DeltaG(H2O, 263 K) = 2.4 +/
1.2 kcal/mol). Collectively, our findings show that the D-scan is powerful new
strategy for studying how the stereochemistry of amino acids affects the
structure and function of proteins.
PMID- 27494077
TI - Subcutaneous anti-TNF alfa induced sustained minimal disease activity and
remission in psoriatic arthritis patients: a retrospective study.
AB - OBJECTIVE: The aim of the present study was to assess the rate of sustained
Minimal Disease Activity (MDA) and remission in a group of psoriatic arthritis
(PsA) patients treated with TNFalpha blockers. METHODS: We perform a
retrospective study on our database of PsA patients treated with adalimumab,
etanercept and golimumab, with a minimum of 12 months of follow up. Patients were
considered in sustained MDA when they met at least 5/7 of the criteria previously
defined for at least 12 months of follow up. DAS28-CRP < 2.6, DAPSA score <= 4
and patient global assessment (PGA) <= 20 mm were also evaluated as remission
criteria. Concordance between the remission criteria and MDA was also performed.
RESULTS: Of the 81 patients treated with TNFalpha blockers, at baseline no
patients were in MDA or had a DAPSA score <= 4, while 17 (20.9%) had a DAS28-CRP
score < 2.6. PGA <= 20 was recorded in 6 patients (7%). Sustained MDA was
achieved in 35 (43.2%) patients while sustained DAPSA, DAS28-CRP and PGA
remission were obtained respectively in 19.7%, 35.8% and 44.4% of patients. No
difference was found between the three anti-TNFalpha in respect to the
probability of achieve MDA. CONCLUSIONS: In this retrospective study, sustained
MDA was achieved in 43.2% of patients treated with TNFalpha blockers. Moreover,
sustained remission was achieved in a consistent number of patients, configuring
this as an achievable target for PsA patients.
PMID- 27494081
TI - "Make Sure You're Not Getting Yourself in Trouble:" Building Sexual Relationships
and Preventing Sexual Violence at the U.S. Military Academy at West Point.
AB - Sexual violence continues to present a problem on college campuses nationwide and
among members of the U.S. military. This study attended to patterns of response
in how students (cadets) at the U.S. Military Academy (West Point) discussed
sexual and romantic relationships, both potential and actual, in order to examine
how, if at all, they enact their sexuality-related values. Constructivist
grounded theory was used to analyze semistructured interviews with three male and
three female cadets from each of the 4 years of the undergraduate program, in
which they are intended to become "leaders of character" who will serve as Army
officers. Findings indicated limitations in cadets' access to developing and
implementing sexuality-related skills within this context. Cadets' fear and
distrust erected barriers to their pursuing their desires; the ways in which
cadets avoided getting in trouble for sexual harassment or sexual assault shifted
responsibility from a potential perpetrator onto a potential victim; and cadets
were caught in dilemmas regarding romantic relationships as sources of both
emotional support and social stigma. These findings have implications for
promoting gender equity and for preventing sexual violence at this institution
and at others like it, including both university campuses and other military
settings.
PMID- 27494080
TI - Raynaud's syndrome in children: systematic review and development of
recommendations for assessment and monitoring.
AB - OBJECTIVES: To develop recommendations for investigation and monitoring of
children with Raynaud's syndrome, based on paediatric evidence collated by a
systematic review. METHODS: A systematic review was undertaken to establish the
paediatric evidence for assessment and monitoring of Raynaud's syndrome. An
expert panel including members of the Paediatric Rheumatology European Society
(PRES) Scleroderma Working Group, were invited to a consensus meeting where
recommendations were developed based on evidence graded by the systematic review
and where evidence was lacking, consensus opinion. A nominal technique was used
where 75% consensus was taken as agreement. RESULTS: The expert panel recommended
testing anti-nuclear antibody (ANA), more specific antibodies associated with
connective tissue disease and nail-fold capillaroscopy in all children presenting
with Raynaud's syndrome as data suggests these can be risk factors for evolution
into a connective tissue disease. The frequency of follow-up recommended depends
on presence of these risk factors with the aim to detect evolving connective
tissue disease early in high risk individuals. Those with no abnormalities on
capillaroscopy and negative autoantibodies were deemed low risk of progression,
whereas those with ANA positivity, specific autoantibodies and/or nailfold
capillary changes were deemed high risk and more frequent follow-up was
recommended. CONCLUSIONS: Recommendations, primarily based on consensus opinion,
were agreed regarding investigation and monitoring of children who present with
Raynaud's syndrome. Further prospective studies are needed to better define the
risk factors for progression to connective tissue disease.
PMID- 27494082
TI - The role of colloidal plasmonic nanostructures in organic solar cells.
AB - Plasmonic particles can contribute via multiple processes to the light absorption
process in solar cells. These particles are commonly introduced into organic
solar cells via deposition techniques such as spin-coating or dip-coating.
However, such techniques are inherently challenging to achieve homogenous surface
coatings as they lack control of inter-particle spacing and particle density on
larger areas. Here we introduce interface assisted colloidal self-assembly as a
concept for the fabrication of well-defined macroscopic 2-dimensional monolayers
of hydrogel encapsulated plasmonic gold nanoparticles. The monolayers showed a
pronounced extinction in the visible wavelength range due to localized surface
plasmon resonance with excellent optical homogeneity. Moreover this strategy
allowed for the investigation of the potential of plasmonic monolayers at
different interfaces of P3HT:PCBM based inverted organic solar cells. In general,
for monolayers located anywhere underneath the active layer, the solar cell
performance decreased due to parasitic absorption. However with thick active
layers, where low hole mobility limited the charge transport to the top
electrode, the plasmonic monolayer near that electrode spatially redistributed
the light and charge generation close to the electrode led to an improved
performance. This work systematically highlights the trade-offs that need to be
critically considered for designing an efficient plasmonically enhanced organic
solar cell.
PMID- 27494079
TI - Pre- and perinatal complications in relation to Tourette syndrome and co
occurring obsessive-compulsive disorder and attention-deficit/hyperactivity
disorder.
AB - Pre- and perinatal complications have been implicated in the onset and clinical
expression of Tourette syndrome albeit with considerable inconsistencies across
studies. Also, little is known about their role in co-occurring obsessive
compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in
individuals with a tic disorder. Therefore, we aimed to investigate the role of
pre- and perinatal complications in relation to the presence and symptom severity
of chronic tic disorder and co-occurring OCD and ADHD using data of 1113
participants from the Tourette International Collaborative Genetics study. This
study included 586 participants with a chronic tic disorder and 527 unaffected
family controls. We controlled for age and sex differences by creating propensity
score matched subsamples for both case-control and within-case analyses. We found
that premature birth (OR = 1.72) and morning sickness requiring medical attention
(OR = 2.57) were associated with the presence of a chronic tic disorder. Also,
the total number of pre- and perinatal complications was higher in those with a
tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the
presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD
severity (b = 1.09). Delivery complications were only related to co-occurring OCD
(OR = 1.49). We conclude that early exposure to adverse situations during
pregnancy is related to the presence of chronic tic disorders. Exposure at a
later stage, at birth or during the first weeks of life, appears to be associated
with co-occurring OCD and ADHD.
PMID- 27494083
TI - Comparison of IOL power calculation formulae for pediatric eyes.
AB - PurposeTo evaluate and compare the accuracy of modern intraocular lens (IOL)
power calculation formulae in pediatric eyes and compare prediction error (PE)
obtained with manufacturer's vs personalized lens constant.Patients and methodsAn
observational case study was conducted in 117 eyes (117 patients) undergoing
pediatric cataract surgery with IOL implantation. PE was calculated as predicted
refraction minus actual postoperative refraction, and absolute PE as absolute
difference independent of the sign, (APE)=predicted refraction minus actual
postoperative refraction. This was done for each formula using manufacturer's and
personalized lens constant. Further, PE and APE were evaluated according to axial
length (AL).ResultsMean age of children was 2.97 years. About 66/117 eyes (56.4%)
were below 2 years of age. Using Holladay 2, Holladay 1, Hoffer Q, and SRK/T
formulae with manufacturer's lens constant, mean PE was 0.36, 0.41, 0.69, and
0.28 diopter (D), respectively. With personalized lens constant, it was 0.16,
0.15, 0.50, and -0.12 D, respectively. Difference in mean PE between the formulae
was statistically significant (P<0.0001). SRK/T and Holladay 2 formulae had the
least PE, both with manufacturer's and personalized constant. For eyes with AL<20
mm, SRK/T and Holladay 2 formulae gave the least PE. Personalizing the lens
constant led to a decrease in mean PE in all formulae, except the Hoffer Q
formula. However, personalizing the lens constant did not significantly improve
the APE. At least 21% eyes had an APE of >2 D with all formulae, even with
personalized lens constants.ConclusionIn pediatric eyes, SRK/T and the Holladay 2
formulae had the least PE. Personalizing the lens formula constant did reduce the
PE significantly for all formulae except Hoffer Q. In extremely short eyes (AL<20
mm), SRK/T and Holladay 2 formulae gave the best PE.
PMID- 27494085
TI - TORCH testing in non-familial paediatric cataract.
PMID- 27494084
TI - Preserved functional and structural integrity of the papillomacular area
correlates with better visual acuity in retinitis pigmentosa.
AB - PurposeLinking multifocal electroretinography (mfERG) and optical coherence
tomography (OCT) findings with visual acuity in retinitis pigmentosa (RP)
patients.DesignProspective, cross-sectional, nonintervention
study.SubjectsPatients with typical RP and age-matched controls, who underwent SD
OCT (spectral domain OCT) and mfERG, were included.MethodsMfERG responses were
averaged in three zones (zone 1 (0 degrees -3 degrees ), zone 2 (3 degrees -8
degrees ), and zone 3 (8 degrees -15 degrees )). Baseline-to-trough- (N1) and
trough-to-peak amplitudes (N1P1) of the mfERG were compared with corresponding
areas of the OCT. The papillomacular area (PMA) was analyzed separately.
Correlations between best-corrected visual acuity (BCVA, logMAR) and each
parameter were determined.Main outcome measuresComparing structural (OCT) and
functional (mfERG) measures with the BCVA.ResultsIn RP patients, the N1 and N1P1
responses showed positive association with the central retinal thickness outside
zone 1 (P<=0.002), while the central N1 and the N1P1 responses in zones 1, 2, and
3-with the BCVA (P<=0.007). The integrity of the IS/OS line on OCT showed also a
positive association with the BCVA (P<0.001). Isolated analysis of the PMA
strengthened further the structure-function association with the BCVA (P<=0.037).
Interactions between the BCVA and the OCT, respectively, the mfERG parameters
were more pronounced in the RP subgroup without macular edema
(P<=0.020).ConclusionIn RP patients, preserved structure-function of PMA,
measured by mfERG amplitude and OCT retinal thickness, correlated well with the
remaining BCVA. The subgroup analyses revealed stronger links between the
examined parameters, in the RP subgroup without appearance of macular edema.
PMID- 27494086
TI - Molecular genetic approaches for environmental stress tolerant crop plants:
Progress and prospects.
AB - Global food security is threatened by the severe environmental conditions that
have reduced the worldwide crop yield. Plants possess inherent mechanisms to cope
with the initial stress phase but to ensure their survival through harsh climate,
the intervention of genetic engineering is desirable. Elucidation of genetic loci
and deciphering the underlying mechanisms that confer tolerance to plants against
stressful conditions followed by its successful introgression into elite, high
yielding crop varieties can be an effective way to engineer the crops for
increasing productivity. This review provides an overview about the effects of
abiotic and biotic stresses on crop plants and the use of genetic engineering
approach to cope with these environmental stresses for a sustainable agriculture.
Major patents in the field of plant stress tolerance in the last five years have
also been summarized.
PMID- 27494087
TI - Ligand Symmetry Modulation for Designing Mixed-Ligand Metal-Organic Frameworks:
Gas Sorption and Luminescence Sensing Properties.
AB - Herein, we report the synthesis of a new mixed-linker Zn(II)-based metal-organic
framework (MOF), {[Zn2(atz)2(bpydb)](DMA)8}n (1) (atz = deprotonated 3-amino
1,2,4-triazole, bpydb = deprotonated 4,4'-(4,4'-bipyridine-2,6-diyl) dibenzoic
acid, DMA = N,N-dimethylacetamide), through symmetry modulation of a triazole
ligand. The desymmetrized triazole linkers not only bond to the Zn(II) ions to
result in a new helical Zn-triazolate chain building unit but also lead to the
formation of a highly porous framework (N2 uptake: 617 cm(3)/g; BET surface area:
2393 m(2)/g) with 1D helical channels. The adsorption properties of desolved 1
were investigated by H2, C2H2, CO2, and CH4 sorption experiments, which showed
that 1 exhibited high uptake capacity for H2 at 77 K and C2H2 around room
temperature. More importantly, the high C2H2 uptake capacity but low binding
energy makes this MOF a promising candidate for effective C2H2 capture from
C2H2/CO2 and C2H2/CH4 mixed gases with low regenerative energy cost. In addition,
1 shows potential application for the luminescence sensing of small aromatic
molecules picric acid (PA) and p-xylene (PX).
PMID- 27494088
TI - Partial recovery of microbiomes after antibiotic treatment.
AB - Antibiotics profoundly affect the gut microbiome and modulate microbial
communities. We recently observed that antimicrobial drugs also impact the
abundance and distribution of antibiotic resistance genes. In this addendum, we
reanalyze our ~1 trillion nucleotide shotgun metagenomic dataset to quantify
comprehensive genomic differences at the sequence level before and after
antibiotic treatment. We show that 7 day exposure to cefprozil leads to a
statistically significant loss of metagenome sequences. Recovery of gut
microbiomes 3 months after antibiotherapy was characterized by the emergence of
new genome sequences not observed prior to antibiotic exposure. Participants with
low initial gut microbiome diversity had an increased amount of sequences related
to antibiotic resistance. Therefore, we suggest that while the taxonomical
composition of microbiomes is partially affected by the antibiotic, the genomic
content and population structure of bacterial communities is noticeably impacted.
PMID- 27494089
TI - Health-related quality of life and patient-reported outcomes of ofatumumab plus
chlorambucil versus chlorambucil monotherapy in the COMPLEMENT 1 trial of
patients with previously untreated CLL.
AB - BACKGROUND: Patients diagnosed with chronic lymphocytic leukemia (CLL) are
usually elderly and frequently have a number of comorbidities. Health-related
quality of life (HRQoL) for these patients is of utmost importance and should be
taken into consideration when assessing new treatment options. The combination of
ofatumumab with chlorambucil has shown longer progression-free survival compared
with chlorambucil alone. In this study, we aim to assess how this treatment
combination affects patients' health-related quality of life and patient-reported
symptoms. MATERIAL AND METHODS: In this open-label phase III trial, patients with
previously untreated CLL for whom fludarabine-based treatment was contra
indicated, were randomized 1:1 to receive oral chlorambucil (10 mg/m2) on Days 1
7 of a 28-day treatment cycle or to receive chlorambucil by this schedule plus
intravenous ofatumumab (Cycle 1: 300 mg on Day 1 and 1000 mg on Day 8; subsequent
cycles: 1000 mg Day 1) for 3-12 cycles. The EORTC QLQ-C30 and QLQ-CLL16
questionnaires were administered to patients before and during treatment, in
follow-up and at the time of disease progression. The primary specified patient
reported outcomes were HRQoL and fatigue. RESULTS: Patient-reported improvements
from baseline in Global Health Status (GHS)/HRQoL scores and fatigue scores were
recorded during treatment with both chlorambucil monotherapy and ofatumumab in
combination with chlorambucil. There were no significant differences between the
two treatment arms for GHS/HRQoL (p = 0.667) or fatigue (p = 0.103). Following
treatment, numerical improvements to GHS/HRQoL and fatigue scores were reported,
with no significant differences between the two treatment arms. CONCLUSION: Small
but detectable improvements in patients' quality of life were reported as a
result of treatment. The addition of ofatumumab to chlorambucil did not
negatively impact HRQoL. Quality of life was maintained in the months following
treatment.
PMID- 27494090
TI - Estimation of salient regions related to chronic gastritis using gastric X-ray
images.
AB - Since technical knowledge and a high degree of experience are necessary for
diagnosis of chronic gastritis, computer-aided diagnosis (CAD) systems that
analyze gastric X-ray images are desirable in the field of medicine. Therefore, a
new method that estimates salient regions related to chronic gastritis/non
gastritis for supporting diagnosis is presented in this paper. In order to
estimate salient regions related to chronic gastritis/non-gastritis, the proposed
method monitors the distance between a target image feature and Support Vector
Machine (SVM)-based hyperplane for its classification. Furthermore, our method
realizes removal of the influence of regions outside the stomach by using
positional relationships between the stomach and other organs. Consequently,
since the proposed method successfully estimates salient regions of gastric X-ray
images for which chronic gastritis and non-gastritis are unknown, visual support
for inexperienced clinicians becomes feasible.
PMID- 27494091
TI - CD3D and PRKCQ work together to discriminate between B-cell and T-cell acute
lymphoblastic leukemia.
AB - Different therapeutic methods have been developed for the B-cell and T-cell
subtypes of acute lymphoblastic leukemia (ALL). The identification of molecular
biomarkers that can accurately discriminate between B-cell and T-cell ALLs will
facilitate the quick determination of therapeutic plans, as well as reveal the
intrinsic mechanisms underlining the two different ALL subtypes. This study
computationally screened the high-throughput transcriptome dataset for multiple
candidate biomarkers and verified their discrimination abilities in an
independent sample set using quantitative real-time polymerase chain reaction
(PCR) technology. Both technologies suggest that the two genes CD3D and PKRCQ
together provided a good model for classification of B-cell and T-cell ALLs,
whereas the individual genes did not show consistent discrimination between the
two ALL subtypes. Supplementary material is available at
http://healthinformaticslab.org/supp/.
PMID- 27494092
TI - Comparison of bone-anchored prostheses and socket prostheses for patients with a
lower extremity amputation: a systematic review.
AB - PURPOSE: This study aimed to provide an overview of a) the used measurement
instruments in studies evaluating effects on quality of life (QoL), function,
activity and participation level in patients with a lower extremity amputation
using bone-anchored prostheses compared to socket prostheses and b) the effects
themselves. METHOD: A systematic literature search was conducted in MEDLINE,
Cochrane, EMBASE, CINAHL and Web of Science. Included studies compared QoL,
function, activity and/or participation level in patients with bone-anchored or
socket prostheses. A best-evidence synthesis was performed. RESULTS: Out of 226
studies, five cohort and two cross-sectional studies were eligible for inclusion,
all had methodological shortcomings. These studies used 10 different measurement
instruments and two separate questions to assess outcome. Bone-anchored
prostheses were associated with better condition-specific QoL and better outcomes
on several of the physical QoL subscales, outcomes on the physical bodily pain
subscale were inconclusive. Outcomes on function and activity level increased, no
change was found at participation level. The level of evidence was limited.
CONCLUSIONS: There is a need for a standard set of instruments. There was limited
evidence that bone-anchored prostheses resulted in higher QoL, function and
activity levels than socket prostheses, in patients with socket-related problems.
Implications for Rehabilitation Use of bone-anchored prostheses in combination
with intensive outpatient rehabilitation may improve QoL, function and activity
level compared with socket prosthesis use in patients with a transfemoral
amputation and socket-related problems. All clinicians and researchers involved
with bone-anchored prostheses should use and publish data on QoL, function,
activity and participation level. There needs to be an agreement on a standard
set of instruments so that interventions for patients with a lower extremity
amputation are assessed consistently.
PMID- 27494093
TI - A novel Bayesian approach to acoustic emission data analysis.
AB - Acoustic emission (AE) technique is a popular tool for materials characterization
and non-destructive testing. Originating from the stochastic motion of defects in
solids, AE is a random process by nature. The challenging problem arises whenever
an attempt is made to identify specific points corresponding to the changes in
the trends in the fluctuating AE time series. A general Bayesian framework is
proposed for the analysis of AE time series, aiming at automated finding the
breakpoints signaling a crossover in the dynamics of underlying AE sources.
PMID- 27494094
TI - Short- and long-term effects of exercise on neck muscle function in cervical
radiculopathy: A randomized clinical trial.
AB - OBJECTIVE: To compare short- and long-term changes in neck muscle endurance,
electromyography measures of neck muscle activation and fatigue and ratings of
fatigue and pain after neck-specific training or physical activity in people with
cervical radiculopathy. DESIGN: Randomized clinical trial. SUBJECTS/PATIENTS:
Seventy-five patients with cervical radiculopathy. METHODS: Patients underwent
neck-specific training in combination with a cognitive behavioural approach or
prescribed physical activity over a period of 14 weeks. Immediately after the
intervention and 12 months later, surface electromyography was recorded from neck
flexor and extensor muscles during neck endurance tests. Time to task failure,
amplitude and median frequency of the electromyography signal, and subjective
fatigue and pain ratings were analysed in 50 patients who completed at least one
follow-up. RESULTS: A significant increase in neck flexor endurance time was
observed for both groups at 14 weeks compared with baseline and this was
maintained at the 12-month follow-up (p < 0.005). No change was identified for
the slope of the median frequency. For the neck-specific training group, splenius
capitis was less active during neck flexion at both follow-ups (p < 0.01),
indicating reduced muscle co-activation. CONCLUSION: Both specific and general
exercise increased neck flexor endurance, but neck-specific training only reduced
co-activation of antagonist muscles during sustained neck flexion.
PMID- 27494095
TI - Applications of large-scale density functional theory in biology.
AB - Density functional theory (DFT) has become a routine tool for the computation of
electronic structure in the physics, materials and chemistry fields. Yet the
application of traditional DFT to problems in the biological sciences is
hindered, to a large extent, by the unfavourable scaling of the computational
effort with system size. Here, we review some of the major software and
functionality advances that enable insightful electronic structure calculations
to be performed on systems comprising many thousands of atoms. We describe some
of the early applications of large-scale DFT to the computation of the electronic
properties and structure of biomolecules, as well as to paradigmatic problems in
enzymology, metalloproteins, photosynthesis and computer-aided drug design. With
this review, we hope to demonstrate that first principles modelling of biological
structure-function relationships are approaching a reality.
PMID- 27494096
TI - Passive Dosing in Chronic Toxicity Tests with the Nematode Caenorhabditis
elegans.
AB - In chronic toxicity tests with Caenorhabditis elegans, it is necessary to feed
the nematode with bacteria, which reduces the freely dissolved concentration
(Cfree) of hydrophobic organic chemicals (HOCs), leading to poorly defined
exposure with conventional dosing procedures. We examined the efficacy of passive
dosing of polycyclic aromatic hydrocarbons (PAHs) using silicone O-rings to
control exposure during C. elegans toxicity testing and compared the results to
those obtained with solvent spiking. Solid-phase microextraction and liquid
liquid extraction were used to measure Cfree and the chemicals taken up via
ingestion. During toxicity testing, Cfree decreased by up to 89% after solvent
spiking but remained constant with passive dosing. This led to a higher apparent
toxicity on C. elegans exposed by passive dosing than by solvent spiking. With
increasing bacterial cell densities, Cfree of solvent-spiked PAHs decreased while
being maintained constant with passive dosing. This resulted in lower apparent
toxicity under solvent spiking but an increased apparent toxicity with passive
dosing, probably as a result of the higher chemical uptake rate via food
(CUfood). Our results demonstrate the utility of passive dosing to control Cfree
in routine chronic toxicity testing of HOCs. Moreover, both chemical uptake from
water or via food ingestion can be controlled, thus enabling the discrimination
of different uptake routes in chronic toxicity studies.
PMID- 27494097
TI - Static and dynamic behaviour of responsive graphene oxide-poly(N-isopropyl
acrylamide) composite gels.
AB - Thermoresponsive hydrogels have enormous potential e.g., as sensors, actuators,
and pollution control remedies or in drug delivery systems. Nevertheless, their
application is often restricted by physical limitations (poor mechanical strength
and uncontrolled thermal response). Composite systems may offer a means of
overcoming these limitations. This paper presents a systematic study of the
structure and dynamics of graphene oxide-poly-(N-isopropylacrylamide) composite
systems, and investigates the effect of the nanoparticle filler content on the
mechanical and swelling properties of the systems. A combination of macroscopic
(swelling and elastic modulus) and microscopic (differential scanning
microcalorimetry, small angle neutron scattering and neutron spin-echo
spectroscopy) investigations reveals that the architecture of the polymer network
is modified by chain nucleation at the surface of the GO platelets, and these
form a percolating network inside the gel. Our results show that the elastic
modulus of the gels is reinforced by the filler, but the mobility of the polymer
chains in the swollen state is practically unaffected. The macroscopic deswelling
of the composites, however, is slowed by the kinetics of ordering in the GO
network.
PMID- 27494098
TI - Tamoxifen and Fulvestrant Hybrids Showed Potency as Selective Estrogen Receptor
Down-Regulators.
AB - BACKGROUND: Estrogen receptors (ERs) are an important target for the management
of breast cancers. Selective estrogen receptor down-regulators (SERDs) block ER
activity, as well as reduce ERalpha protein levels in cells, and therefore are
promising therapeutic agents for the treatment of breast cancers. OBJECTIVE: In
order to develop potent SERDs, we prepared tamoxifen and fulvestrant hybrids and
evaluated their binding activity and down-regulation of ERalpha. METHODS: We
designed and synthesized tamoxifen derivatives, which had a 4,4,5,5,5-
pentafluoropentyl group on the terminal alkyl chain. The oxidation state of the
sulfur atom and alkyl length between the sulfur and nitrogen atoms were varied.
Western blotting was performed to determine the ability to down-regulate ERalpha.
Binding affinities of synthesized compounds were evaluated by a fluorescence
polarization-based competitive binding assay. RESULTS: We successfully prepared
nine compounds. Treatment with 11, 14, and 17 effectively reduced ERalpha protein
levels in MCF-7 cells in a concentration-dependent manner. This reduction was
inhibited by a proteasome inhibitor. The ability of 14 to down-regulate the
ERalpha protein level was equal to fulvestrant. All compounds showed a largely
equal affinity for ERalpha. CONCLUSION: As indicated by Western blots, the
ERalpha degradation activity was observed only in the series of butyl linker
derivatives, namely, 11, 14, and 17. These findings suggest that the specific
length of the alkyl chain is an important factor in controlling the down
regulation of ER. These results provide useful information for designing
promising SERD candidates.
PMID- 27494099
TI - Fabrication of granular activated carbons derived from spent coffee grounds by
entrapment in calcium alginate beads for adsorption of acid orange 7 and
methylene blue.
AB - Biomass-based granular activated carbon was successfully prepared by entrapping
activated carbon powder derived from spent coffee grounds into calcium-alginate
beads (SCG-GAC) for the removal of acid orange 7 (AO7) and methylene blue (MB)
from aqueous media. The dye adsorption process is highly pH-dependent and
essentially independent of ionic effects. The adsorption kinetics was
satisfactorily described by the pore diffusion model, which revealed that pore
diffusion was the rate-limiting step during the adsorption process. The
equilibrium isotherm and isosteric heat of adsorption indicate that SCG-GAC
possesses an energetically heterogeneous surface and operates via endothermic
process in nature. The maximum adsorption capacities of SCG-GAC for AO7 (pH 3.0)
and MB (pH 11.0) adsorption were found to be 665.9 and 986.8mg/g at 30 degrees C,
respectively. Lastly, regeneration tests further confirmed that SCG-GAC has
promising potential in its reusability, showing removal efficiency of more than
80% even after seven consecutive cycles.
PMID- 27494100
TI - Effect of actinobacteria agent inoculation methods on cellulose degradation
during composting based on redundancy analysis.
AB - In this study, actinobacteria agent including Streptomyces sp. and Micromonospora
sp. were inoculated during chicken manure composting by different inoculation
methods. The effect of different treatments on cellulose degradation and the
relationship between inoculants and indigenous actinobacteria were investigated
during composting. The results showed that inoculation in different stages of
composting all improved the actinobacteria community diversity particularly in
the cooling stage of composting (M3). Moreover, inoculation could distinctly
accelerate the degradation of organic matters (OM) especially celluloses.
Redundancy analysis indicated that the correlation between indigenous
actinobacteria and degradation of OM and cellulose were regulated by inoculants
and there were significant differences between different inoculation methods.
Furthermore, synergy between indigenous actinobacteria and inoculants for
degradation of OM and cellulose in M3 was better than other treatments.
Conclusively, we suggested an inoculation method to regulate the indigenous
actinobacteria based on the relationship between inoculants and indigenous
actinobacteria and degradation content.
PMID- 27494102
TI - The role of residual quantities of suspended sludge on nitrogen removal
efficiency in a deammonifying moving bed biofilm reactor.
AB - In a moving bed biofilm reactor (MBBR) system, the vast majority of biomass is
immobilized as biofilm besides small amounts of suspension. In this study, the
influence of the individual biomass components of a deammonifying MBBR, the
biofilm on carriers (BC), residual suspended biomass (SB) with a volatile
suspended solids concentration of 0.09+/-0.03g/L, and its combination (BC+SB) on
nitrogen removal efficiency was investigated. While the performance was highest
for BC+SB (0.42kgN/(m(3).d)), it was reduced by a factor of 3.5 for BC solely. SB
itself was only capable of nitrite accumulation. This suggests a high abundance
of AOBs within suspension besides the coexistence of AOBs and anammox bacteria in
the biofilm, which could be supported by results using fluorescence in situ
hybridization(FISH). Thus, small amounts of suspended microorganisms can
positively influence the deammonification's efficiency. If this fraction is
partially washed out, the system recovers nevertheless within hours.
PMID- 27494101
TI - Successions and diversity of humic-reducing microorganisms and their association
with physical-chemical parameters during composting.
AB - Humic-reducing microorganisms (HRMs) could utilize humic substances (HS) as
terminal electron mediator to promote the biodegradation of recalcitrant
pollutants. However, the dynamics of HRMs during composting has not been
explored. Here, high throughput sequencing technology was applied to investigate
the patterns of HRMs during three composting systems. A total of 30 main genera
of HRMs were identified in three composts, with Proteobacteria being the largest
phylum. HRMs were detected with increased diversity and abundance and distinct
patterns during composting, which were significantly associated with dissolved
organic carbon, dissolved organic nitrogen and germination index. Regulating key
physical-chemical parameters is a process control of HRMs community composition,
thus promoting the redox capability of the compost. The redox capability of HRMs
were strengthened during composting, suggesting that HRMs of the compost may play
an important role on pollutant degradation of the compost or when they are
applied to the contaminated soils.
PMID- 27494103
TI - Co-production of carbonic anhydrase and phycobiliproteins by Spirulina sp. and
Synechococcus nidulans.
AB - The aim of this work was to study the co-production of the carbonic anhydrase, C
phycocyanin and allophycocyanin during cyanobacteria growth. Spirulina sp. LEB 18
demonstrated a high potential for simultaneously obtaining the three products,
achieving a carbonic anhydrase (CA) productivity of 0.97U/L/d and the highest C
phycocyanin (PC, 5.9MUg/mL/d) and allophycocyanin (APC, 4.3MUg/mL/d)
productivities. In the extraction study, high extraction yields were obtained
from Spirulina using an ultrasonic homogenizer (CA: 25.5U/g; PC: 90mg/g; APC:
70mg/g). From the same biomass, it was possible to obtain three biomolecules that
present high industrial value.
PMID- 27494105
TI - Production of bioactive protein hydrolysate using the yeasts isolated from soft
chhurpi.
AB - The aim of this work was to study the production of bioactive protein
hydrolysates using yeasts isolated from chhurpi. For this, a total of 125
proteolytic yeasts were isolated and molecular identification was carried out by
analysis of the restriction digestion pattern generated by digesting the PCR
amplified internal transcribed spacer region and 5.8S rRNA gene (ITS1-5.8S-ITS2)
using three endonucleases (HaeIII, CfoI and HinfI). The results obtained showed
that different proteolytic yeasts were dominant in marketed products
(Kluyveromyces marxianus and Issatchenkia orientalis) and samples from production
centers (Trichosporon asahii, Saccharomyces cerevisiae and Exophiala
dermatitidis). Proteolytic strains in individual groups showed their ability to
hydrolyze milk protein and enhance antioxidant property. Among the isolates,
fermentation using K. marxianus YMP45 and S. cerevisiae YAM14 resulted in higher
antioxidant activity. This is the first report on application of yeast isolated
from fermented food of North-East India for the production of bioactive protein
hydrolysate.
PMID- 27494104
TI - Biogas production generated through continuous digestion of natural and
cultivated seaweeds with dairy slurry.
AB - The technical feasibility of long term anaerobic mono-digestion of two brown
seaweeds, and co-digestion of both seaweeds with dairy slurry was investigated
whilst increasing the organic loading rate (OLR). One seaweed was natural (L.
digitata); the second seaweed (S. Latissima) was cultivated. Higher proportions
of L. digitata in co-digestion (66.6%) allowed the digester to operate more
efficiently (OLR of 5kgVSm(-3)d(-1) achieving a specific methane yield (SMY) of
232LCH4kg(-1)VS) as compared to lower proportions (33.3%). Co-digestion of 66.6%
cultivated S. latissima, with dairy slurry allowed a higher SMY of 252LCH4kg(
1)VS but at a lower OLR of 4kgVSm(-3)d(-1). Optimum conditions for mono-digestion
of both seaweeds were effected at 4kgVSm(-3)d(-1). Chloride concentrations
increased to high levels in the digestion of both seaweeds but were not
detrimental to operation.
PMID- 27494106
TI - Light intensity impacts the production of biofuel intermediates in Heterosigma
akashiwo growing on simulated flue gas containing carbon dioxide and nitric
oxide.
AB - As a potential biofuel feedstock, the marine microalga, Heterosigma akashiwo,
accumulates significant lipids, is capable of long-term growth in outdoor
photobioreactors, and is an excellent candidate for the bioremediation of
industrial emissions. Here, we evaluated resource partitioning in H. akashiwo
growing on a CO2 and NO gas mixture under three light intensities: 160, 560, or
1200MUmolquantam(-2)s(-1). Light levels had no effect on growth; however,
cultures in high light accumulated 2.3-fold more carbohydrates and 17% fewer
lipids. Light levels did not affect the percentage of saturated fatty acids, but
mono-unsaturates increased by 6% and poly-unsaturates decreased by 12% in high
light. The fatty acid profiles reported here suggest that H. akashiwo is a good
candidate for the production of neutral lipids for biodiesel and also omega-3
fatty acids, and that the quality of biodiesel acquired from feedstocks grown
under fluctuating light conditions would be relatively stable.
PMID- 27494107
TI - Asthma control and productivity loss in those with work-related asthma: A
population-based study.
AB - OBJECTIVE: In Canada, asthma is the third leading cause of work loss, yet little
is known about the associated productivity loss. The goal of this study was to
look at the relationship between asthma control and productivity loss,
particularly contrasting those with work-related asthma (WRA) and non-work
related asthma (NWRA). METHODS: A population-based random sample of adults with
asthma in British Columbia, Canada, was prospectively recruited. Asthma control
was graded according to Global Initiative for Asthma classification, while
productivity loss and presence of WRA was assessed using questionnaires. Ordinal
regression models were then used to associate WRA with asthma control.
Generalized linear models were applied to estimate the average productivity loss
associated with different levels of asthma control among those with WRA and NWRA.
RESULTS: The study included 300 employed adults. Sixty (20%) had WRA. The odds of
being controlled were significantly lower in those with WRA (OR = 0.23, 95% CI:
0.09, 0.56; P < 0.01). Those with WRA and uncontrolled asthma had a significant
difference in productivity loss due to presenteeism ($659.1 [95% CI: 12.9,
1581.5; P = 0.04]), but not absenteeism ($88.7 [95% CI: -86.5, 279.6; P = 0.35]),
when compared to those with NWRA and uncontrolled asthma. There was no
significant difference when a similar comparison was made for those with
controlled or partially controlled asthma. CONCLUSIONS: WRA is associated with
worse asthma control and increased productivity loss. Presenteeism makes a
significant contribution to productivity loss and should be considered when
evaluating the overall economic burden of asthma, particularly WRA.
PMID- 27494108
TI - Successful low-dose leflunomide treatment for ganciclovir-resistant
cytomegalovirus infection with high-level antigenemia in a kidney transplant: A
case report and literature review.
AB - Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for
organ transplant recipients. Foscarnet is an alternative, although it may
potentially worsen the preexistent impaired renal function. Here we report the
case of a successful low-dose leflunomide treatment in a kidney transplant
recipient with very high viral replication, who underwent kidney transplantation
10 years before. Administering 10mg leflunomide daily for 5 months without a
loading dose completely cleared the ganciclovir-resistant cytomegalovirus
strains.
PMID- 27494109
TI - Ischemic post-conditioning attenuates renal ischemic reperfusion injury via down
regulation of toll-like receptor 4 in diabetic rats.
AB - BACKGROUND: Ischemia/reperfusion (I/R) injury, which is commonly seen in the
field of renal surgery or transplantation, is a major cause of acute renal
failure (ARF). The ischemic ARF in diabetic rats is much more severe than that in
the normal rats exposed to as same ischemic time. Ischemic post-conditioning
(IPO) is a phenomenon by which intermittent interruptions of blood flow in the
early phase of reperfusion can protect organs from I/R injury. To determine
whether the renal protection effect of IPO mediates by toll-like receptor 4
(TLR4) signaling pathway in diabetic rats. METHODS: Streptozotocin-induced
diabetic rats were randomly divided into three groups: sham operation group, I/R
group, and IPO group. Except sham operation group, rats were subjected to 30 min
of renal ischemia, both with and without treatment with IPO, then reperfusion 24
h. Light microscope and transmission electronic microscope were used to observe
structural changes of renal tubule. RT-PCR was used to measure TLR4 and tumor
necrosis factor-alpha (TNF-alpha) mRNA expression level, renal TLR4 and nuclear
factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) protein
expression was detected by Western blot. RESULTS: The results demonstrated that
IPO markedly decreased renal ischemic injury caused by I/R and inhibited the
proinflammatory expression levels of TLR4, TNF-alpha, and NF-kappaB, all of which
up-regulated by I/R in diabetic rats. CONCLUSION: Taken together, our results
suggest that proper IPO may have protective effect on the ischemic injury
mediated by renal I/R, which might be associated with inhibition of TLR4
signaling pathway in diabetic rats.
PMID- 27494110
TI - A Two-Step Absorber Deposition Approach To Overcome Shunt Losses in Thin-Film
Solar Cells: Using Tin Sulfide as a Proof-of-Concept Material System.
AB - As novel absorber materials are developed and screened for their photovoltaic
(PV) properties, the challenge remains to reproducibly test promising candidates
for high-performing PV devices. Many early-stage devices are prone to device
shunting due to pinholes in the absorber layer, producing "false-negative"
results. Here, we demonstrate a device engineering solution toward a robust
device architecture, using a two-step absorber deposition approach. We use tin
sulfide (SnS) as a test absorber material. The SnS bulk is processed at high
temperature (400 degrees C) to stimulate grain growth, followed by a much
thinner, low-temperature (200 degrees C) absorber deposition. At a lower process
temperature, the thin absorber overlayer contains significantly smaller, densely
packed grains, which are likely to provide a continuous coating and fill pinholes
in the underlying absorber bulk. We compare this two-step approach to the more
standard approach of using a semi-insulating buffer layer directly on top of the
annealed absorber bulk, and we demonstrate a more than 3.5* superior shunt
resistance Rsh with smaller standard error sigmaRsh. Electron-beam-induced
current (EBIC) measurements indicate a lower density of pinholes in the SnS
absorber bulk when using the two-step absorber deposition approach. We correlate
those findings to improvements in the device performance and device performance
reproducibility.
PMID- 27494112
TI - Expression profiles of MGMT, p16, and APC genes in tumor and matching surgical
margin from patients with oral squamous cell carcinoma.
AB - The aim of the study was to assess the expression of MGMT, p16, and APC genes in
tumors and matching surgical margin samples from 56 patients with primary OSCC.
We also analyzed the association of the clinical variables with the expression of
the studied genes. After RNA isolation and cDNA synthesis gene expression levels
were assessed by quantitative reverse transcription (qRT)-PCR. Two-sided
parametrical Student's t-test for independent groups with equal/unequal variances
showed no statistically significant differences in genes' expression in tumor
compared to margin samples. No association was found between the genes'
expression and clinical parameters, except for MGMT, whose low expression was
probably associated with smoking (0.87 vs 1.34, p=0.065). 'Field cancerization'
is an area with genetically or epigenetically altered cells and at the same time
a risk factor for cancer. Disturbances in gene expression could also be the
source of damages leading to cancerization. In conclusion, it is important to
mention that the field remaining after a surgery may pose an increased risk of
cancer development. It may be suggested that the diagnosis and treatment of
cancers should not be concentrated only on the tumor itself, but also on the
cancer field effect. Therefore, further molecular analysis on surgical margins
and additional research regarding their assessment are required.
PMID- 27494113
TI - The perplexities of the ZC3H12A self-mRNA regulation.
AB - The mechanisms regulating transcript turnover are key processes in the regulation
of gene expression. The list of proteins involved in mRNAs' degradation is still
growing, however, the details of RNase-mRNAs interactions are not fully
understood. ZC3H12A is a recently discovered inflammation-related RNase engaged
in the control of proinflammatory cytokine transcript turnover. ZC3H12A also
regulates its own transcript half-live. Here, we studied the details of this
regulation. Our results confirm the importance of the 3'UTR in ZC3H12A-dependent
ZC3H12A mRNA degradation. We compared the mouse and human stemloop structures
present in this region and discovered that the human conserved stem-loop
structure is not sufficient for ZC3H12A-dependent degradation. However, this
structure is important for the ZC3H12A mRNA post-transcriptional regulation. Our
studies emphasize the importance of the neighboring features of the identified
stem-loop structure for its biological activity. Removal of this region together
with the stem-loop structure greatly inhibits the ZC3H12A regulation of the
investigated 3'-untranslated region (3'UTR).
PMID- 27494111
TI - Prognostic Impact of Time to Ipsilateral Breast Tumor Recurrence after Breast
Conserving Surgery.
AB - BACKGROUND: The poor prognosis of patients who experience ipsilateral breast
tumor recurrence (IBTR) after breast conserving surgery (BCS) is established. A
short time between primary cancer and IBTR is a prognostic factor but no
clinically relevant threshold was determined. Classification of IBTR may help
tailor treatment strategies. PURPOSE: We determined a specific time frame, which
differentiates IBTR into early and late recurrence, and identified prognostic
factors for patients with IBTR at time of the recurrence. METHODS: We analyzed
2209 patients with IBTR after BCS. We applied the optimal cut-points method for
survival data to determine the cut-off times to IBTR. A subgroup analysis was
performed by hormone receptor (HR) status. Survival analyses were performed using
a Cox proportional hazard model to determine clinical features associated with
distant-disease-free survival (DDFS) after IBTR. We therefor built decision
trees. RESULTS: On the 828 metastatic events observed, the majority occurred
within the first 3 months after IBTR: 157 in the HR positive group, 98 in the HR
negative group. We found different prognostic times to IBTR: 49 months in the HR
positive group, 33 in the HR negative group. After multivariate analysis, time to
IBTR was the first discriminant prognostic factor in both groups (HR 0.65 CI95%
[0.54-0.79] and 0.42 [0.30-0.57] respectively). The other following variables
were significantly correlated with the DDFS: the initial number of positive lymph
nodes for both groups, the initial tumor size and grade for HR positive tumors.
CONCLUSION: A short interval time to IBTR is the strongest factor of poor
prognosis and reflects occult distant disease. It would appear that prognosis
after IBTR depends more on clinical and histological parameters than on surgical
treatment. A prospective trial in a low-risk group of patients to validate the
safety of salvage BCS instead of mastectomy in IBTR is needed.
PMID- 27494114
TI - Nonparametric Model of Smooth Muscle Force Production During Electrical
Stimulation.
AB - A nonparametric model of smooth muscle tension response to electrical stimulation
was estimated using the Laguerre expansion technique of nonlinear system kernel
estimation. The experimental data consisted of force responses of smooth muscle
to energy-matched alternating single pulse and burst current stimuli. The burst
stimuli led to at least a 10-fold increase in peak force in smooth muscle from
Mytilus edulis, despite the constant energy constraint. A linear model did not
fit the data. However, a second-order model fit the data accurately, so the
higher-order models were not required to fit the data. Results showed that smooth
muscle force response is not linearly related to the stimulation power.
PMID- 27494115
TI - A review of the relative efficacy of dietary, nutritional supplements, lifestyle,
and drug therapies in the management of hypertension.
AB - Despite advancements in hypertensive therapies, the prevalence of hypertension
and associated morbidities are still immense. Physicians are in great need for
updated information on novel and effective antihypertensive therapies. Therefore,
the study objective was to provide comprehensive information on the efficacy of
available antihypertensive therapies. Antihypertensive therapies were divided
into four general approaches: diet, nutritional supplements, lifestyle
modification, and conventional antihypertensive medications. A search of PubMed
and Google Scholar resulted in an analysis of 30 antihypertensive therapies from
meta-analyses and randomized-controlled trials (RCTs). The studies were analyzed
using the American Heart Association/American College of Cardiology
classification system. Calculated average blood pressure reductions were:
(systolic/diastolic) 6/4 mmHg, 4/2 mmHg, 5/3 mmHg, and 9/5 mmHg for dietary,
nutritional supplements, lifestyle, and medications, respectively. The results
demonstrate that dietary, nutritional supplement and lifestyle strategies have a
solid level of evidence to support their efficacy as antihypertensive strategies.
These strategies can be as effective as medications and, in some cases, even more
effective. Dissemination of this information to physicians/dietitians can help
facilitate an important shift in hypertension management.
PMID- 27494116
TI - Dual-Mode Luminescent Nanopaper Based on Ultrathin g-C3N4 Nanosheets Grafted with
Rare-Earth Upconversion Nanoparticles.
AB - Ultrathin graphite-like carbon nitride (g-C3N4) nanosheets have attracted
considerable attention due to the enhanced intrinsic photoabsorption and
photoresponse with respect to bulk g-C3N4. For the first time, a dual-mode of
down- and upconversion luminescent g-C3N4 nanopaper with high optical
transparency and mechanical robustness was successfully fabricated through a
simple thermal evaporation process using chitosan as a green cross-linking agent.
The dual-mode of down- and upconversion fluorescence emission originated from the
amino terminated ultrathin g-C3N4 nanosheets functionalized with carboxylic acid
modified multicolored rare-earth upconversion nanoparticles (cit-UCNPs) via
EDC/NHS coupling chemistry. The homogeneously distributed cit-UCNPs@g-C3N4
nanoconjugates with excellent hydrophilicity displayed good film-forming ability
and structural integrity; thus, the photoluminescence of each ingredient was
substantially maintained. Results indicated that the freestanding chitosan cross
linked cit-UCNPs@g-C3N4 luminescent nanopaper possessed high transmittance,
excellent mechanical properties, and remarkable dual-mode emission. The smart
design of high performance luminescent nanopaper based on ultrathin g-C3N4
nanosheets grafted with multicolored UCNPs offers a potential strategy to
immobilize other multifunctional luminescent materials for easily recognizable
and hardly replicable anticounterfeiting fields.
PMID- 27494117
TI - Modified AS1411 Aptamer Suppresses Hepatocellular Carcinoma by Up-Regulating
Galectin-14.
AB - Aptamers are small synthetic oligonucleotides that bind to target proteins with
high specificity and affinity. AS1411 is an aptamer that binds to nucleolin,
which is overexpressed in the cytoplasm and occurs on the surface of cancer
cells. We investigated the therapeutic potential of aptamers in hepatocellular
carcinoma (HCC) by evaluating anti-tumor effects and confirming the affinity and
specificity of AS1411- and modified AS1411-aptamers in HCC cells. Cell growth was
assessed using the MTS assay, and cell death signaling was explored by immunoblot
analysis. Fluorescence-activated cell sorting was performed to evaluate the
affinity and specificity of AS1411-aptamers in SNU-761 HCC cells. We investigated
the in vivo effects of the AS1411-aptamer using BALB/c nude mice in a
subcutaneous xenograft model with SNU-761 cells. Treatment with a modified AS1411
aptamer significantly decreased in vitro (under normoxic [P = 0.035] and hypoxic
[P = 0.018] conditions) and in vivo (under normoxic conditions, P = 0.041) HCC
cell proliferation compared to control aptamers. AS1411- and control aptamers
failed to control HCC cell proliferation. However, AS1411- and the modified
AS1411-aptamer did not induce caspase activation. Decrease in cell growth by
AS1411 or modified AS1411 was not prevented by caspase or necrosis inhibitors. In
a microarray, AS1411 significantly enhanced galectin-14 expression. Suppression
of HCC cell proliferation by the modified AS1411-aptamer was attenuated by
galectin-14 siRNA transfection. Modified AS1411-aptamer suppressed HCC cell
growth in vitro and in vivo by up-regulating galectin-14 expressions. Modified
AS1411-aptamers may have therapeutic potential as a novel targeted therapy for
HCC.
PMID- 27494118
TI - Estimating patient specific uncertainty parameters for adaptive treatment re
planning in proton therapy using in vivo range measurements and Bayesian
inference: application to setup and stopping power errors.
AB - In proton therapy, quantification of the proton range uncertainty is important to
achieve dose distribution compliance. The promising accuracy of prompt gamma
imaging (PGI) suggests the development of a mathematical framework using the
range measurements to convert population based estimates of uncertainties into
patient specific estimates with the purpose of plan adaptation. We present here
such framework using Bayesian inference. The sources of uncertainty were modeled
by three parameters: setup bias m, random setup precision r and water equivalent
path length bias u. The evolution of the expectation values E(m), E(r) and E(u)
during the treatment was simulated. The expectation values converged towards the
true simulation parameters after 5 and 10 fractions, for E(m) and E(u),
respectively. E(r) settle on a constant value slightly lower than the true value
after 10 fractions. In conclusion, the simulation showed that there is enough
information in the frequency distribution of the range errors measured by PGI to
estimate the expectation values and the confidence interval of the model
parameters by Bayesian inference. The updated model parameters were used to
compute patient specific lateral and local distal margins for adaptive re
planning.
PMID- 27494120
TI - The use of neutron scattering to determine the functional structure of glycoside
hydrolase.
AB - Neutron diffraction provides different information from X-ray diffraction,
because neutrons are scattered by atomic nuclei, whereas X-rays are scattered by
electrons. One of the key advantages of neutron crystallography is the ability to
visualize hydrogen and deuterium atoms, making it possible to observe the
protonation state of amino acid residues, hydrogen bonds, networks of water
molecules and proton relay pathways in enzymes. But, because of technical
difficulties, less than 100 enzyme structures have been evaluated by neutron
crystallography to date. In this review, we discuss the advantages and
disadvantages of neutron crystallography as a tool to investigate the functional
structure of glycoside hydrolases, with some examples.
PMID- 27494121
TI - Identification and screening of chemical constituents with hepatoprotective
effects from three traditional Chinese medicines for treating jaundice.
AB - The constituents with hepatoprotective activity were investigated in three
traditional Chinese medicine formulae for treating jaundice, namely, Zhi-Zi-Da
Huang-Tang, Yin-Chen-Hao-Tang, and Da-Huang-Xiao-Shi-Tang. By using liquid
chromatography coupled with quadrupole time-of-flight mass spectrometry and
liquid chromatography coupled with ion trap mass spectrometry, 79 chemical
constituents were identified unambiguously or tentatively in three formulae based
on the accurate molecular weight, mass spectrometric fragmentation behavior, and
comparison with reference standards. Then the hepatoprotective activities of 27
constituents were evaluated on tert-butylhydroperoxide-injured BRL-3A cells. The
results indicated that 11 constituents, including protocatechic acid (19),
epijasminoside A (56), rutin (71), tetrahydropalmatine (76), rhaponticin (80),
3,4-dicaffeoylquinic acid (82), 3,5-dicaffeoylquinic acid (85), diosmetin-7-O
glucoside (90), jatrorrhizine (93), berberine (100), and daidzein (101) exerted
hepatoprotective activities. Interestingly, most of the crude drugs in three
formulae contained hepatoprotective active constituents, and the combinations of
constituents from different crude drugs exhibited greater effects. This result
provided evidence to the traditional Chinese medicine theory of combining several
drugs together to exert synergistic efficacy.
PMID- 27494122
TI - Nonempirical Double-Hybrid Functionals: An Effective Tool for Chemists.
AB - Density functional theory (DFT) emerged in the last two decades as the most
reliable tool for the description and prediction of properties of molecular
systems and extended materials, coupling in an unprecedented way high accuracy
and reasonable computational cost. This success rests also on the development of
more and more performing density functional approximations (DFAs). Indeed, the
Achilles' heel of DFT is represented by the exchange-correlation contribution to
the total energy, which, being unknown, must be approximated. Since the beginning
of the 1990s, global hybrids (GH) functionals, where an explicit dependence of
the exchange-correlation energy on occupied Kohn-Sham orbitals is introduced
thanks to a fraction of Hartree-Fock-like exchange, imposed themselves as the
most reliable DFAs for chemical applications. However, if these functionals
normally provide results of sufficient accuracy for most of the cases analyzed,
some properties, such as thermochemistry or dispersive interactions, can still be
significantly improved. A possible way out is represented by the inclusion, into
the exchange-correlation functional, of an explicit dependence on virtual Kohn
Sham orbitals via perturbation theory. This leads to a new class of functionals,
called double-hybrids (DHs). In this Account, we describe our nonempirical
approach to DHs, which, following the line traced by the Perdew-Burke-Ernzerhof
approach, allows for the definition of a GH (PBE0) and a DH (QIDH) model. In such
a way, a whole family of nonempirical functionals, spanning on the highest rungs
of the Perdew's quality scale, is now available and competitive with other-more
empirical-DFAs. Discussion of selected cases, ranging from thermochemistry and
reactions to weak interactions and excitation energies, not only show the large
range of applicability of nonempirical DFAs, but also underline how increasing
the number of theoretical constraints parallels with an improvement of the DFA's
numerical performances. This fact further consolidates the strong theoretical
framework of nonempirical DFAs. Finally, even if nonempirical DH approaches are
still computationally expensive, relying on the fact that they can benefit of all
technical enhancements developed for speeding up post-Hartree-Fock methods, there
is substantial hope for their near future routine application to the description
and prediction of complex chemical systems and reactions.
PMID- 27494119
TI - A Comprehensive Evaluation of Steroid Metabolism in Women with Intrahepatic
Cholestasis of Pregnancy.
AB - Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly
occurring in the third trimester. ICP is defined as an elevation of serum bile
acids, typically accompanied by pruritus and elevated activities of liver
aminotransferases. ICP is caused by impaired biliary lipid secretion, in which
endogenous steroids may play a key role. Although ICP is benign for the pregnant
woman, it may be harmful for the fetus. We evaluated the differences between
maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its
sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids),
hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile
acids (TBA) >8 MUM) and corresponding controls (n = 17). An age-adjusted linear
model, receiver-operating characteristics (ROC), and multivariate regression (a
method of orthogonal projections to latent structure, OPLS) were used for data
evaluation. While aminotransferases, conjugates of pregnanediols, 17
hydroxypregnenolone and 5beta-androstane-3alpha,17beta-diol were higher in ICP
patients, 20alpha-dihydropregnenolone, 16alpha-hydroxy-steroids, sulfated 17-oxo
C19-steroids, and 5beta-reduced steroids were lower. The OPLS model including
steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity,
while the model including steroids measured by GC-MS in a single sample aliquot
showed 93.3% sensitivity and 94.1% specificity. A composite index including
ratios of sulfated 3alpha/beta-hydroxy-5alpha/beta-androstane-17-ones to
conjugated 5alpha/beta-pregnane-3alpha/beta, 20alpha-diols discriminated with
93.3% specificity and 81.3% sensitivity (ROC analysis). These new data
demonstrating altered steroidogenesis in ICP patients offer more detailed
pathophysiological insights into the role of steroids in the development of ICP.
PMID- 27494123
TI - Un/Paid Labor: Medicaid Home and Community Based Services Waivers That Pay Family
as Personal Care Providers.
AB - The United States long-term services and supports system is built on largely
unpaid (informal) labor. There are a number of benefits to allowing family
caregivers to serve as paid personal care providers including better health and
satisfaction outcomes, expanded workforces, and cost effectiveness. The purpose
of this study was to examine how Medicaid HCBS Section 1915(c) waivers for people
with intellectual and developmental disabilities allocate personal care services
to pay family caregivers. Our analysis revealed about two thirds of waivers in
fiscal year (FY) 2014 allowed for family caregivers to potentially be paid for
personal care services. This amounted to up to $2.71 billion of projected
spending, which is slightly more than half of all personal care service
expenditures in FY 2014.
PMID- 27494124
TI - Exploring the Self-Disclosure Process in Peer Mentoring Relationships for
Transition-Age Youth With Developmental Disabilities.
AB - The purpose of this study was to examine the role of the self-disclosure process
in regard to connection development and relationship quality in peer mentoring
relationships between transition-age youth (ages 15-20) and young adults (ages 18
36) with intellectual and/or developmental disabilities. Self-disclosure is
defined as "the disclosure of inner feelings and experiences to another person"
that "fosters liking, caring, and trust, thereby facilitating the deepening of
close relationships" ( Reis & Shaver, 1988 , p. 372). Nine peer mentoring dyads
with varied interpersonal connections were purposefully selected from a larger
intervention study. Recorded mentoring conversations were analyzed for self
disclosure content and peer mentor response. The findings demonstrated trends
related to connection development and differences across degree of connection. In
relationships with stronger connections, there was a higher quantity of self
disclosure and more frequent disclosure of emotions, and peer mentors responded
more frequently with advice and reciprocated self-disclosure. Implications of
findings for promoting higher-quality peer mentoring relationships are discussed.
PMID- 27494126
TI - Smith-Magenis Syndrome and Social Security Administration's Compassionate
Allowances Initiative: An Evaluative Review of the Literature.
AB - The Social Security Administration (SSA) launched the Compassionate Allowances
List (CAL) in 2008. This created a mechanism for expediting review and delivery
of disability benefits, while decreasing application backlog. This study
hypothesized that developmental disorders, such as Smith-Magenis syndrome, may
meet criterion for inclusion. An evaluative review of the literature was
undertaken to determine if the expedited review criterion was met. Ten databases
were searched and articles meeting pre-defined criteria were coded according to
the SSA definition of disability to determine if severity indices screen in or
screen out certain severity levels or exclude Smith-Magenis syndrome entirely in
relation to the CAL program. It was strongly recommended that Smith-Magenis
syndrome receive consideration for inclusion in the CAL.
PMID- 27494125
TI - Parent Involvement in Meaningful Post-School Experiences for Young Adults With
IDD and Pervasive Support Needs.
AB - Despite initiatives supporting young adults with intellectual and developmental
disabilities (IDD) to engage in post-secondary education and integrated
employment, those with more intensive support needs are not as easily involved in
these post-school experiences. In an effort to learn from positive examples, we
examined parent involvement in meaningful post-school experiences by eight young
adults with IDD and pervasive support needs. Secondary analysis of data from a
prior interview study yielded this smaller sample of eight young adults with
meaningful post-school experiences. Their parents were actively involved as
fierce advocates and creative problem solvers. The active involvement of parents
included: a) attitudinal facilitators, b) advocacy efforts and perceptions, and
c) strategic actions. Implications for future research and practice are
described.
PMID- 27494127
TI - "My Voice Counts, Too": Voting Participation Among Individuals With Intellectual
Disability.
AB - Despite a strong societal commitment to ensuring that individuals with
intellectual disability (ID) fully participate in their communities, few people
with ID vote. Little is known about voting experiences from the perspective of
people with ID. In-person, semistructured interviews were conducted with 28
adults with ID (Mage = 37 years) to obtain their input on voting. Constant
comparison and content analysis methods were used to characterize themes. Results
indicated that people with ID are interested in voting and desire to be included
in the voting process yet receive little education on political issues or on how
to make voting-related decisions. Support from family or service providers and
self-advocacy facilitated their ability to vote. Implications of these findings
and recommendations for future research are discussed.
PMID- 27494130
TI - Detection of Zika virus in Brazilian patients during the first five days of
infection - urine versus plasma.
AB - Advantages of testing for Zika virus (ZIKV) in urine have been reported, such as
the persistence of ZIKV in this type of specimen for up to 20 days after ZIKV
disease onset. We investigate 61 patients in the first 5 days post-symptom onset
and find more patients testing positive for ZIKV in plasma samples (n=46), than
in corresponding urine samples (n=37). For patients respectively testing positive
in both plasma and urine (n=28), respective viral loads appeared similar.
PMID- 27494131
TI - Fluoride-Assisted Synthesis of 1,4,5,6-Tetrahydropyridazines via [4 + 2]
Cyclodimerization of in Situ-Generated Azoalkenes Followed by a C-N Bond
Cleavage.
AB - An unexpected CsF-assisted C-N bond cleavage was exploited to synthesize highly
functionalized and biologically important 1,4,5,6-tetrahydropyridazine
derivatives from alpha-halo N-acylhydrazones in excellent yields. The extrusion
of nitrogen and the [4 + 2] cycloaddition between in situ-generated azoalkenes is
a key reaction in the process. The identified methodology is suitable for
synthesizing a wide variety of analogues of tetrahydropyridazines, which are
prevalent in many medicinally important small molecules. The reaction conditions
are mild, high-yielding, and amenable for the gram scale.
PMID- 27494132
TI - Estimating initial contaminant mass based on fitting mass-depletion functions to
contaminant mass discharge data: Testing method efficacy with SVE operations
data.
AB - The mass of contaminant present at a site, particularly in the source zones, is
one of the key parameters for assessing the risk posed by contaminated sites, and
for setting and evaluating remediation goals and objectives. This quantity is
rarely known and is challenging to estimate accurately. This work investigated
the efficacy of fitting mass-depletion functions to temporal contaminant mass
discharge (CMD) data as a means of estimating initial mass. Two common mass
depletion functions, exponential and power functions, were applied to historic
soil vapor extraction (SVE) CMD data collected from 11 contaminated sites for
which the SVE operations are considered to be at or close to essentially complete
mass removal. The functions were applied to the entire available data set for
each site, as well as to the early-time data (the initial 1/3 of the data
available). Additionally, a complete differential-time analysis was conducted.
The latter two analyses were conducted to investigate the impact of limited data
on method performance, given that the primary mode of application would be to use
the method during the early stages of a remediation effort. The estimated initial
masses were compared to the total masses removed for the SVE operations. The mass
estimates obtained from application to the full data sets were reasonably similar
to the measured masses removed for both functions (13 and 15% mean error). The
use of the early-time data resulted in a minimally higher variation for the
exponential function (17%) but a much higher error (51%) for the power function.
These results suggest that the method can produce reasonable estimates of initial
mass useful for planning and assessing remediation efforts.
PMID- 27494133
TI - Identification of Cell Type-Specific Differences in Erythropoietin Receptor
Signaling in Primary Erythroid and Lung Cancer Cells.
AB - Lung cancer, with its most prevalent form non-small-cell lung carcinoma (NSCLC),
is one of the leading causes of cancer-related deaths worldwide, and is commonly
treated with chemotherapeutic drugs such as cisplatin. Lung cancer patients
frequently suffer from chemotherapy-induced anemia, which can be treated with
erythropoietin (EPO). However, studies have indicated that EPO not only promotes
erythropoiesis in hematopoietic cells, but may also enhance survival of NSCLC
cells. Here, we verified that the NSCLC cell line H838 expresses functional
erythropoietin receptors (EPOR) and that treatment with EPO reduces cisplatin
induced apoptosis. To pinpoint differences in EPO-induced survival signaling in
erythroid progenitor cells (CFU-E, colony forming unit-erythroid) and H838 cells,
we combined mathematical modeling with a method for feature selection, the L1
regularization. Utilizing an example model and simulated data, we demonstrated
that this approach enables the accurate identification and quantification of cell
type-specific parameters. We applied our strategy to quantitative time-resolved
data of EPO-induced JAK/STAT signaling generated by quantitative immunoblotting,
mass spectrometry and quantitative real-time PCR (qRT-PCR) in CFU-E and H838
cells as well as H838 cells overexpressing human EPOR (H838-HA-hEPOR). The
established parsimonious mathematical model was able to simultaneously describe
the data sets of CFU-E, H838 and H838-HA-hEPOR cells. Seven cell type-specific
parameters were identified that included for example parameters for nuclear
translocation of STAT5 and target gene induction. Cell type-specific differences
in target gene induction were experimentally validated by qRT-PCR experiments.
The systematic identification of pathway differences and sensitivities of EPOR
signaling in CFU-E and H838 cells revealed potential targets for intervention to
selectively inhibit EPO-induced signaling in the tumor cells but leave the
responses in erythroid progenitor cells unaffected. Thus, the proposed modeling
strategy can be employed as a general procedure to identify cell type-specific
parameters and to recommend treatment strategies for the selective targeting of
specific cell types.
PMID- 27494134
TI - ESBL Detection: Comparison of a Commercially Available Chromogenic Test for Third
Generation Cephalosporine Resistance and Automated Susceptibility Testing in
Enterobactericeae.
AB - Rapid detection and reporting of third generation cephalosporine resistance (3GC
R) and of extended spectrum betalactamases in Enterobacteriaceae (ESBL-E) is a
diagnostic and therapeutic priority to avoid inefficacy of the initial antibiotic
regimen. In this study we evaluated a commercially available chromogenic screen
for 3GC-R as a predictive and/or confirmatory test for ESBL and AmpC activity in
clinical and veterinary Enterobacteriaceae isolates. The test was highly reliable
in the prediction of cefotaxime and cefpodoxime resistance, but there was no
correlation with ceftazidime and piperacillin/tazobactam minimal inhibitory
concentrations. All human and porcine ESBL-E tested were detected with exception
of one genetically positive but phenotypically negative isolate. By contrast,
AmpC detection rates lay below 30%. Notably, exclusion of piperacillin/tazobactam
resistant, 3GC susceptible K1+ Klebsiella isolates increased the sensitivity and
specificity of the test for ESBL detection. Our data further imply that in
regions with low prevalence of AmpC and K1 positive E. coli strains chromogenic
testing for 3GC-R can substitute for more time consuming ESBL confirmative
testing in E. coli isolates tested positive by Phoenix or VITEK2 ESBL screen. We,
therefore, suggest a diagnostic algorithm that distinguishes 3GC-R screening from
primary culture and species-dependent confirmatory ESBL testing by betaLACTATM
and discuss the implications of MIC distribution results on the choice of
antibiotic regimen.
PMID- 27494135
TI - Truncated Bovine Integrin Alpha-v/Beta-6 as a Universal Capture Ligand for FMD
Diagnosis.
AB - Foot-and-mouth disease (FMD) is endemic in many regions of the world and is one
of the most prevalent epizootic animal diseases. FMD affects livestock, such as
cattle, sheep, goats and pigs, and causes enormous economic losses due to reduced
productivity and trade restrictions. Preparedness and early diagnosis are
essential for effective control of FMD. Many diagnostic assays are dependent on
raising high-affinity, anti-FMD virus (FMDV) serotype-specific antibodies in
small animals (rabbits and guinea pigs) that give broad virus coverage. Here we
show that soluble, truncated forms of bovine alphavbeta6 bind FMDV in an
authentic RGD and divalent cation dependent interaction and can be used as the
trapping reagent in a FMDV sandwich ELISA. In addition, inclusion of FLAG or His
tags facilitates simple purification without the loss of virus binding. We also
provide evidence that when combined with a guinea pig polyclonal serum, or
serotype-specific monoclonal antibodies, the integrin can be used to detect
viruses representative of all FMDV serotypes. We also show that recombinant FMDV
empty capsids, with stabilising disulphide bonds, can serve as an antigen in the
ELISA and can therefore replace inactivated virus antigen as a positive control
for the assay. Our results demonstrate the potential use of bovine alphavbeta6
and FMDV empty capsids in FMD diagnostic assays.
PMID- 27494136
TI - Assessing Interventions to Manage West Nile Virus Using Multi-Criteria Decision
Analysis with Risk Scenarios.
AB - The recent emergence of West Nile virus (WNV) in North America highlights
vulnerability to climate sensitive diseases and stresses the importance of
preventive efforts to reduce their public health impact. Effective prevention
involves reducing environmental risk of exposure and increasing adoption of
preventive behaviours, both of which depend on knowledge and acceptance of such
measures. When making operational decisions about disease prevention and control,
public health must take into account a wide range of operational, environmental,
social and economic considerations in addition to intervention effectiveness. The
current study aimed to identify, assess and rank possible risk reduction measures
taking into account a broad set of criteria and perspectives applicable to the
management of WNV in Quebec under increasing transmission risk scenarios, some of
which may be related to ongoing warming in higher-latitude regions. A
participatory approach was used to collect information on categories of concern
to relevant stakeholders with respect to WNV prevention and control. Multi
criteria decision analysis was applied to examine stakeholder perspectives and
their effect on strategy rankings under increasing transmission risk scenarios.
Twenty-three preventive interventions were retained for evaluation using eighteen
criteria identified by stakeholders. Combined evaluations revealed that, at an
individual-level, inspecting window screen integrity, wearing light colored, long
clothing, eliminating peridomestic larval sites and reducing outdoor activities
at peak times were top interventions under six WNV transmission scenarios. At a
regional-level, the use of larvicides was a preferred strategy in five out of six
scenarios, while use of adulticides and dissemination of sterile male mosquitoes
were found to be among the least favoured interventions in almost all scenarios.
Our findings suggest that continued public health efforts aimed at reinforcing
individual-level preventive behaviours combined with the application of
larvicides to manage the risk of WNV infection are the interventions most
acceptable and effective at reaching current management objectives now and under
future theoretical transmission risk.
PMID- 27494137
TI - Enantioselective Model Synthesis and Progress toward the Putative Structure of
Yuremamine.
AB - An enantioselective model synthesis of the 2,3-dihydro-1H-pyrrolo[1,2-a]indole
core of the putative structure of yuremamine is reported in 39% overall yield and
96% ee over five steps. The model synthesis leverages enantioselective, rhodium
catalyzed hydroacylation of an N-vinylindole-2-carboxaldehyde as the key step in
the installation of the stereochemical triad. An enantioselective synthesis of a
densely functionalized dihydropyrroloindolone that maps onto the putative
structure of yuremamine is demonstrated in 26% yield and 97% ee over eight steps.
PMID- 27494138
TI - Extended Thermodynamic Integration: Efficient Prediction of Lambda Derivatives at
Nonsimulated Points.
AB - Thermodynamic integration (TI) is one of the most commonly used free-energy
calculation methods. The derivative of the Hamiltonian with respect to lambda,
??H/?lambda?, is determined at multiple lambda-points. Because a numerical
integration step is necessary, high curvature regions require simulations at
densely spaced lambda-points. Here, the principle of extended TI is introduced,
where ??H/?lambda? values are predicted at nonsimulated lambda-points. On the
basis of three model systems, it is shown that extended TI requires significantly
fewer lambda-points than regular TI to obtain similar accuracy.
PMID- 27494139
TI - Etiology of Pain and Its Association with Quality of Life among Patients with
Heart Failure.
AB - OBJECTIVE: Describe the etiology of pain among HF patients and examine the
relationship between pain and QoL. BACKGROUND: Little is known about the etiology
of pain in patients with heart failure (HF) and the impact it has on quality of
life (QoL). METHODS: A prospective cohort study of outpatients with NYHA Class II
or III HF were surveyed at baseline and at three-month follow-up. The study was
conducted in Heart Failure clinics affiliated with a large, urban, academic
medical center. RESULTS: Of 104 patients that completed a baseline survey, 73
(70%) completed a follow-up survey. At baseline, 48% of patients reported having
pain the previous week. Patients on prescription pain medication (n = 16) had
more severe pain (Mean = 4.5 vs. 2.6; p = 0.001). Physician documented pain
etiologies included: musculoskeletal (50%, n = 16), cardiac (22%, n = 7), and
headache/neurological (22%, n = 7). Linear regression revealed that significant
contributions to QoL included HF Class (p = 0.0001), dyspnea (p = 0.0001), and
depression (p = 0.01). Pain was not independently associated with QoL (p = 0.17),
but moderately correlated with depression (r = 0.49). Although 15% (n = 11) of
patients reported a clinically meaningful improvement in pain scores, it was not
associated with improvements in QoL (chi2 = 1.6, p = 0.2). DISCUSSION: Pain is
prevalent and persistent, due largely to non-cardiac causes. Although pain did
not predict QOL, it was associated with depression, which did adversely affect
QoL. Clinicians should screen for and treat both symptoms.
PMID- 27494140
TI - Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism
of Damage Triggered by Auto-Antibodies.
AB - Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP)
are heterogeneous. This study describes increased platelet apoptosis involving
loss of mitochondrial membrane potential (DeltaPsim), caspase 3 activation
(aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP
patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P
selectin exposure and GPIb-IX internalization were not increased. Besides, ITP
platelets were more sensitive to apoptotic stimulus in terms of aCasp3.
Incubation of normal platelets with ITP plasma induced loss of DeltaPsim, while
PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed
in ITP platelets could be reproduced in normal platelets incubated with ITP
plasma by adding normal CD3+ lymphocytes to the system as effector cells.
Addition of leupeptin -a cathepsin B inhibitor- to this system protected
platelets from apoptosis. Increased PS exposure was also observed when normal
platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients
and was absent when ITP plasma was depleted of auto-antibodies, pointing to the
latter as responsible for platelet damage. Apoptosis was present in platelets
from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was
absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage
inversely correlated with platelet count and decreased during treatment with a
thrombopoietin receptor agonist. These results point to a key role for auto
antibodies in platelet apoptosis and suggest that antibody-dependent cell
cytotoxicity is the mechanism underlying this phenomenon.
PMID- 27494141
TI - Osteopontin Fragments with Intact Thrombin-Sensitive Site Circulate in Cervical
Cancer Patients.
AB - We investigated whether circulating osteopontin (OPN) could be used as a
biomarker for cervical cancer. We employed a monoclonal antibody (mAb 659)
specific for the unique and intact thrombin-sensitive site in OPN using an
inhibition ELISA. We found significantly higher levels of OPN in 33 cervical
cancer patients in both the plasma (mean +/- SD, 612 +/- 106 ng/mL) and serum
(424 +/- 121 ng/mL) compared to healthy subjects [409 +/- 56 ng/mL, from 31
plasma samples (P < 0.0001), and 314 +/- 98 ng/mL, from 32 serum samples (P =
0.0002), respectively]. Similar results were obtained when the plasma from a
bigger group (147 individuals) of cervical cancer patients (560 +/- 211 ng/mL)
were compared with the same plasma samples of the healthy individuals (P =
0.0014). More significantly, the OPN level was highest in stage III-IV disease
(614 +/- 210 ng/mL, from 52 individuals; P = 0.0001) and least and non
discriminatory in stage I (473 +/- 110 ng/mL, from 40 individuals; P = 0.5318).
No such discrimination was found when a mAb of a different specificity (mAb 446)
was used in a similar inhibition ELISA to compare the two groups in the first
study; a commercial capture ELISA also failed. The possibility that the target
epitope recognized by the antibody probe in these assays was absent from the
circulating OPN due to protein truncation was supported by gel fractionation of
the OPN found in patients' plasma: 60-64 kDa fragments were found instead of the
presumably full-length OPN (68 kDa) seen in healthy people. How these fragments
are generated and what possible role they play in cancer biology remain
interesting questions.
PMID- 27494143
TI - Correction: 3'UTR Shortening Potentiates MicroRNA-Based Repression of Pro
differentiation Genes in Proliferating Human Cells.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1005879.].
PMID- 27494142
TI - The Neural Responses to Social Cooperation in Gain and Loss Context.
AB - Cooperation is pervasive and constitutes the core behavioral principle of human
social life. Previous studies have revealed that mutual cooperation was reliably
correlated with two reward-related brain regions, the ventral striatum and the
orbitofrontal cortex. Using functional magnetic resonance imaging (fMRI), this
study sought to investigate how the loss and gain contexts modulated the neural
responses to mutual cooperation. Twenty-five female participants were scanned
when they played a series of one-shot prisoner's dilemma games in the loss and
gain contexts. Specifically, participants and partners independently chose to
either cooperate with each other or not, and each was awarded or deprived of (in
the gain context or the loss context, respectively) a sum of money which depended
upon the interaction of their choices. Behavioral results indicated that
participants cooperated in nearly half of the experiment trials and reported
higher level of positive emotions for mutual cooperation in both contexts, but
they cooperated more in the gain than in the loss context. At the neural level,
stronger activities in the orbitofrontal cortex were observed for mutual
cooperation compared with the other three outcomes in both contexts, while
stronger activation in ventral striatum associated with mutual cooperation was
observed in the gain context only. Together, our data indicated that, even in the
one-shot interaction under loss context, participants still exhibited preference
for cooperation and the rewarding experience from a mutually cooperative social
interaction activated the ventral striatum and the orbitofrontal cortex, but the
loss context weakened the association between the ventral striatum activation and
mutual cooperation.
PMID- 27494145
TI - Evidence for the contribution of a threshold retrieval process to semantic
memory.
AB - It is widely held that episodic retrieval can recruit two processes: a threshold
context retrieval process (recollection) and a continuous signal strength process
(familiarity). Conversely the processes recruited during semantic retrieval are
less well specified. We developed a semantic task analogous to single-item
episodic recognition to interrogate semantic recognition receiver-operating
characteristics (ROCs) for a marker of a threshold retrieval process. We fitted
observed ROC points to three signal detection models: two models typically used
in episodic recognition (unequal variance and dual-process signal detection
models) and a novel dual-process recollect-to-reject (DP-RR) signal detection
model that allows a threshold recollection process to aid both target
identification and lure rejection. Given the nature of most semantic questions,
we anticipated the DP-RR model would best fit the semantic task data. Experiment
1 (506 participants) provided evidence for a threshold retrieval process in
semantic memory, with overall best fits to the DP-RR model. Experiment 2 (316
participants) found within-subjects estimates of episodic and semantic threshold
retrieval to be uncorrelated. Our findings add weight to the proposal that
semantic and episodic memory are served by similar dual-process retrieval
systems, though the relationship between the two threshold processes needs to be
more fully elucidated.
PMID- 27494146
TI - Benefits of subthalamic stimulation for elderly parkinsonian patients aged 70
years or older.
AB - OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an
accepted treatment for advanced Parkinson disease (PD). However, there is general
reluctance in considering this therapy for PD patients over age 70 years with
limited supporting evidence. Present study investigates age impacts in STN-DBS
outcomes, focusing particularly on the elderly patients. PATIENTS AND METHODS:
Seventy-two consecutive patients were divided into younger and elderly (n=16,
cutoff age=70years) groups. Both groups were comparable in preoperative clinical
severity, except the elderly exhibited a levodopa (LD) response (P<0.05) inferior
to that of the younger. Improvements in drug-off/DBS-on Unified PD Rating Scale
(UPDRS) scores and reduction in daily LD-equivalent dose (LED) after 6 months
were evaluated relative to the presurgical drug-off baseline. Preoperative
factors predictive of favorable surgical outcomes were analyzed using a
multivariate linear regression model. RESULTS: After DBS therapy, elderly
patients exhibited clinical improvements particularly in the tremor (56%) and LD
induced dyskinesia (78%). Improvement of axial dysfunction (24%) and reduction of
daily LED (24%) showed no intergroup difference. Adverse events, particularly
dysarthria, occurred frequently in elderly group. The overall improvements in
UPDRS scores were suboptimal in elderly group, correlating with their
preoperative inferior LD responses. Elderly patients who presented predominantly
with akinesia before surgery achieved superior surgical outcomes (adjusted
R(2)=0.657, P<0.001). CONCLUSION: STN-DBS therapy is beneficial to some elderly
PD patients aged 70 years or older. Tremor, axial dysfunctions and drug-induced
dyskinesia are the main indications for the elderly; however, their clinical
benefits are inferior to those of younger patients.
PMID- 27494144
TI - Dysbiosis of the Fecal Microbiota in Cattle Infected with Mycobacterium avium
subsp. paratuberculosis.
AB - Johne's disease (JD) is a chronic, intestinal infection of cattle, caused by
Mycobacterium avium subsp. paratuberculosis (MAP). It results in granulomatous
inflammation of the intestinal lining, leading to malabsorption, diarrhea, and
weight loss. Crohn's disease (CD), a chronic, inflammatory gastrointestinal
disease of humans, has many clinical and pathologic similarities to JD. Dysbiosis
of the enteric microbiota has been demonstrated in CD patients. It is speculated
that this dysbiosis may contribute to the intestinal inflammation observed in
those patients. The purpose of this study was to investigate the diversity
patterns of fecal bacterial populations in cattle infected with MAP, compared to
those of uninfected control cattle, using phylogenomic analysis. Fecal samples
were selected to include samples from 20 MAP-positive cows; 25 MAP-negative
herdmates; and 25 MAP-negative cows from a MAP-free herd. The genomic DNA was
extracted; PCR amplified sequenced on a 454 Roche platform, and analyzed using
QIIME. Approximately 199,077 reads were analyzed from 70 bacterial communities
(average of 2,843 reads/sample). The composition of bacterial communities
differed between the 3 treatment groups (P < 0.001; Permanova test). Taxonomic
assignment of the operational taxonomic units (OTUs) identified 17 bacterial
phyla across all samples. Bacteroidetes and Firmicutes constituted more than 95%
of the bacterial population in the negative and exposed groups. In the positive
group, lineages of Actinobacteria and Proteobacteria increased and those of
Bacteroidetes and Firmicutes decreased (P < 0.001). Actinobacteria was highly
abundant (30% of the total bacteria) in the positive group compared to exposed
and negative groups (0.1-0.2%). Notably, the genus Arthrobacter was found to
predominate Actinobacteria in the positive group. This study indicates that MAP
infected cattle have a different composition of their fecal microbiota than MAP
negative cattle.
PMID- 27494147
TI - Reply to Arguelles.
PMID- 27494148
TI - DICERing macrophages for reprogramming TAMs.
PMID- 27494150
TI - Interview with Professor Mark Wilcox.
AB - Mark Wilcox speaks to Georgia Patey, Commissioning Editor: Professor Mark Wilcox
is a Consultant Microbiologist and Head of Microbiology at the Leeds Teaching
Hospitals (Leeds, UK), the Professor of Medical Microbiology at the University of
Leeds (Leeds, UK), and is the Lead on Clostridium difficile and the Head of the
UK C. difficile Reference Laboratory for Public Health England (PHE). He was the
Director of Infection Prevention (4 years), Infection Control Doctor (8 years)
and Clinical Director of Pathology (6 years) at the Leeds Teaching Hospitals. He
is Chair of PHE's Rapid Review Panel (reviews utility of infection prevention and
control products for National Health Service), Deputy Chair of the UK Department
of Health's Antimicrobial Resistance and Healthcare Associated Infection
Committee and a member of PHE's HCAI/AR Programme Board. He is a member of
UK/European/US working groups on C. difficile infection. He has provided clinical
advice as part of the FDA/EMA submissions for the approval of multiple novel
antimicrobial agents. He heads a healthcare-associated infection research team at
University of Leeds, comprising approximately 30 doctors, scientists and nurses;
projects include multiple aspects of C. difficile infection, diagnostics,
antimicrobial resistance and the clinical development of new antimicrobial
agents. He has authored more than 400 publications, and is the coeditor of
Antimicrobial Chemotherapy (5th/6th/7th Editions, 15 December 2007).
PMID- 27494149
TI - Respiratory Muscle Strength as a Predictive Biomarker for Survival in Amyotrophic
Lateral Sclerosis.
AB - RATIONALE: Biomarkers for survival in amyotrophic lateral sclerosis (ALS) would
facilitate the development of novel drugs. Although respiratory muscle weakness
is a known predictor of poor prognosis, a comprehensive comparison of different
tests is lacking. OBJECTIVES: To compare the predictive power of invasive and
noninvasive respiratory muscle strength assessments for survival or ventilator
free survival, up to 3 years. METHODS: From a previously published report
respiratory muscle strength measurements were available for 78 patients with ALS.
Time to death and/or ventilation were ascertained. Receiver operating
characteristic analysis was used to determine the cutoff point of each parameter.
MEASUREMENTS AND MAIN RESULTS: Each respiratory muscle strength assessment
individually achieved statistical significance for prediction of survival or
ventilator-free survival. In multivariate analysis sniff trans-diaphragmatic and
esophageal pressure, twitch trans-diaphragmatic pressure (Tw Pdi), age, and
maximal static expiratory mouth pressure were significant predictors of
ventilation-free survival and Tw Pdi and maximal static expiratory mouth pressure
for absolute survival. Although all measures had good specificity, there were
differing sensitivities. All cutoff points for the VC were greater than 80% of
normal, except for prediction of 3-month outcomes. Sequential data showed a
linear decline for direct measures of respiratory muscle strength, whereas VC
showed little to no decline until 12 months before death/ventilation.
CONCLUSIONS: The most powerful biomarker for mortality stratification was Tw Pdi,
but the predictive power of sniff nasal inspiratory pressure was also excellent.
A VC within normal range suggested a good prognosis at 3 months but was of little
other value.
PMID- 27494152
TI - Household Food Insecurity Is Associated with Nutritional Status among Iranian
Children.
AB - This cross-sectional study was conducted to determine household food security
status and sociodemographic factors influencing it and to examine whether food
insecurity of household is a risk factor for underweight, stunting, and thinness
in primary school children of Sistan and Baluchestan Province in southeastern
Iran. A sample of 610 students aged 7-11 years was selected by a multistage
cluster random sampling method during December 2013-May 2014. Using U.S.
Department of Agriculture Food Security questionnaire, 42.3% of households showed
some degree of food insecurity. Food insecurity was positively associated with
household size (p = .002) and number of children per household (p = .001) and
negatively associated with mother's and father's education level (p = .005 and p
= .042, respectively), father's occupation status, and household income (p <
.0001). Children living in food insecure with severe hunger households were
10.13, 10.07, and 4.54 times as likely to be underweight, stunted, and thin,
respectively, as counterparts from food secure households. The findings showed
food insecurity was prevalent and associated with sociodemographic factors among
households with schoolchildren in southeastern Iran. Nutritional status of
children was also associated with food security status of their households.
PMID- 27494151
TI - Amyotrophic lateral sclerosis with long lasting disease course and SOD1 and
TARDBP mutations: Report of two cases and overview of the literature.
PMID- 27494153
TI - Tagging the Untaggable: A Difluoroalkyl-Sulfinate Ketone-Based Reagent for Direct
C-H Functionalization of Bioactive Heteroarenes.
AB - We have developed a new difluoroalkyl ketal sulfinate salt reagent suitable for
direct derivatization of heteroarene C-H bonds. The reagent is capable of
introducing a ketone functional group on heteroarene bioactive compounds via a
one-pot reaction. Remarkably, in three examples the ketone analog and its parent
drug had almost identical cytotoxicity. In a representative example, the ketone
analog was bioconjugated with a delivery vehicle via an acid-labile semicarbazone
linkage and with a photolabile protecting group to produce the corresponding
prodrug. Controlled release of the drug-ketone analog was demonstrated in vitro
for both systems. This study provides a general approach to obtain taggable
ketone analogs directly from bioactive heteroarene compounds with limited options
for conjugation. We anticipate that this sodium ketal-sulfinate reagent will be
useful for derivatization of other heteroarene-based drugs to obtain ketone
taggable analogs with retained efficacy.
PMID- 27494155
TI - Comparative study on the in vitro performance of blister molded and conventional
lornoxicam immediate release liquitablets: accelerated stability study and anti
inflammatory and ulcerogenic effects.
AB - CONTEXT: Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID). It
shows limited solubility in the gastric pH, delayed bioavailability and
pharmacodynamic effects with aggravated gastric side effects (due to longer
residence in the stomach wall). OBJECTIVE: To enhance dissolution of lornoxicam
in the gastric fluid and expectedly absorption and pharmacological action, with
less ulcerogenic effects. MATERIALS AND METHODS: Formulation of immediate release
(IR) lornoxicam liquitablets containing both liquid and solid release modulators
(wetting agent, solubilizers and microenvironmental pH modifiers). Beside the
traditional direct compression technique employed for the preparation of
liquitablets a new technique, blister molding, was also used. The effect of the
two different manufacturing methods on the fast release characteristics (rapid
disintegration and dissolution) was studied. Stability and pharmacological
activity of the optimum formula were also explored. RESULTS: Similarity factor
pointed out the superiority of molding technique in enhancing dissolution of
lornoxicam owing to significant crystallinity reduction (XRD). Optimum formula
showed negligible change in drug content and dissolution profiles over 12 weeks,
significantly improved anti-inflammatory activity and significantly reduced
gastric ulcerative effect over pure lornoxicam and commercial formula. DISCUSSION
AND CONCLUSION: Blister molded lornoxicam liquitablet of improved dissolution and
pharmacological activity and less gastric erosion was successfully prepared.
PMID- 27494156
TI - Clinical features and management of erythromelalgia: long term follow-up of 46
cases.
AB - OBJECTIVES: To review our clinical experience of this rare condition and describe
the clinical features and response to therapy in a cohort of patients with
erythromelalgia (EM), a rare condition, characterised by paroxysmal hyperthermia
of the extremities with erythema, pain and intense burning. METHODS: A review was
made of the electronic and paper medical records of patients with the diagnosis
of EM, with a telephone interview to verify and complete clinical information
relating treatment and outcome. RESULTS: 46 patients (41 females) were included
in this study. Mean age was 57 years and mean duration of symptoms was 16 years.
Raynaud's phenomenon was present in 36 patients (80%) and 4 patients (9%) had
systemic sclerosis. Smoking (current or previous) was identified as a possible
risk factor in 26 cases and exposure to chronic vibration in 3 cases. Overall,
the effect on quality of life was mild in 15% of cases, moderate in 30% and
severe in 48%. The most common symptoms were burning (96%), heat (93%), pain
(87%), and redness (83%). Symptoms affected the lower limbs in 98% of cases,
upper limbs in 76%, face in 20% and trunk in 11%. Triggers included heat (85%),
exercise (78%) and time of day (76%). Various medications were tried, showing
poor effect in most cases. Intravenous iloprost was given to 27 patients, with
benefit in 17 patients (63%). CONCLUSIONS: Erythromelalgia is a rare chronic
debilitating condition. Exercise, heat and night time are common triggers.
Current medical therapies are seldom effective and further research is sorely
needed.
PMID- 27494157
TI - Advances and Potential Applications of Chitosan Nanoparticles as a Delivery
Carrier for the Mucosal Immunity of Vaccine.
AB - BACKGROUND: Drug research and development has entered into the new epoch of
innovation formulation, and the drug delivery system has been in the forefront of
pharmaceutical innovation. Chitosan, a natural polysaccharide derived from
chitin, due to its well-known biocompatibility and biodegradability, it has been
widely used in drug delivery, immunostimulation, tissue regeneration, blood
coagulation, wound healing, drug delivery and tissue engineering. Chitosan has
become a valuable vaccine adjuvant and delivery carrier, which have attracted
increasing attention for its applications. In this paper, we reviewed chitosan
nanoparticles, which is a promising biomaterial as vaccine adjuvant and delivery
carrier, including characteristics, preparation methods and applications, or even
its limitations. We also investigated the mucosal immune delivery route for drug
loaded chitosan nanoparticles, such as the routes of oral and nasal. Due to the
low toxicity, better biodegradability and adhesivity of chitosan nanoparticles,
it can be used as the delivery carrier of vaccine antigens and drugs. These
promising studies laid a foundation for the applications of chitosan
nanoparticles as a delivery carrier in the vaccine or drug. METHODS: We undertook
a structured research of biodegradable polymeric nanoparticles of chitosan used
as a delivery carrier for the mucosal immunity of vaccine. We have searched the
bibliographic databases for peer-reviewed research literature. The outstanding
characteristics of the screened papers were described respectively, and a
systematic content analysis methodology was used to analyse the findings.
RESULTS: Sixty-three papers were included in the review, the majority defined
leadership and governance approaches that had impacted upon the polymeric
nanoparticles as the delivery carrier for the mucosal immunity of vaccine in
therapeutic applications and developments. Thirty-five papers outlined the
superiority characteristics of chitosan nanoparticles that applied in the field
of vaccine. Twenty-eight papers overviewed the application prospects of chitosan
derivatives used as drug delivery systerm. These included current advances in
research and clinical applications of chitosan derivatives. This review
identified the drug delivery systerm of chitosan or its derivatives, and we
described the synthesis methods, applications and challenges of chitosan.
CONCLUSION: The findings of this review identified that the chitosan derivatives
were used as delivery carrier for vaccines. It also indicates that the chitosan
or its derivatives play a vital role in the drug and vaccine delivery systerm.
PMID- 27494158
TI - Evaluation of Lipopeptides as Toll-like Receptor 2 Ligands.
AB - BACKGROUND: Peptide-based vaccines are considered to be the next generation of
modern immunizations, as they are safe, easy to produce and well-defined.
However, due to their weak immunogenic effect, it is important to first develop
an appropriate adjuvant for peptide-based vaccines. OBJECTIVE: The aim of this
work was to synthesize a series of four adjuvanting moieties as alkyne
derivatives, incorporating dipalmitoyl serine (DPS), 1,3-diglyceride (DG), two
hexadecane lipoamino acids (diLAA), and 2,3-dipalmitoyl-S-glycerylcysteine
(Pam2Cys). Next aim was to synthesize and attach the azide derivative of
biotinylated J14 peptide (model B-cell epitope) to the alkynes through copper-
catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC) reaction. Final aim was
to test the ability of the final biotin labeled conjugates to directly interact
with in vitro expressed TLR2 and 8 using AlphaScreen proximity assay. METHOD: All
of the peptides were synthesized by manual stepwise solid phase peptide synthesis
(SPPS) on rink amide MBHA resin using HATU/DIPEA Fmoc-chemistry. The target
compounds were synthesized in a solution phase using CuAAC reaction. RESULTS:
Pam2Cys analogue bound to TLR2 as expected. Analogues of DPS and C16-LAA showed
also affinity to TLR2, while it did not bind to the control protein (TLR8),
demonstrating ability of the DPS and C16-LAA to be recognized by TLR2.
CONCLUSION: Four alkyne derivatives of lipids were successfully synthesized and
coupled to a biotinylated J14 peptide to give a series of self-adjuvanting
ligands. These ligands showed different affinity to TLR2 upon testing by
AlphaScreen assay. The DPS derivative showed the most promising affinity in
comparison to the standard TLR2 agonist, Pam2Cys.
PMID- 27494159
TI - Review: The Role of MOP and DOP Receptors in Treatment of Diarrheapredominant
Irritable Bowel Syndrome.
AB - Diarrhea-predominant irritable bowel syndrome (IBS-D) is a frequent functional
disorder of the gastrointestinal (GI) tract affecting nearly one fifth of the
worldwide population. IBS-D is associated with numerous symptoms including
diarrhea, bloating, abdominal pain and discomfort, which significantly reduce
patients' quality of life. Due to a complex and unclear pathogenesis, effective
therapy against IBS-D has not been developed yet. Nowadays, treatment is focused
on non-pharmacological (e.g. changes in diet and life style) and pharmacological
(e.g. loperamide, ramosetron, rifaximin) approaches. The endogenous opioid system
is responsible for the maintenance of homeostasis in the GI tract. Activation of
the intestinal opioid receptors (ORs), in particular MU (MOP) and delta (DOP)
results in reduction of epithelial secretion and increase of water/electrolyte
absorption; moreover, opioids are strong analgesic agents. Thus, ligands of ORs
are a promising target in IBS-D treatment. In this review, we discuss the role of
ORs in the pathogenesis of IBS-D and the use of "classical" and novel, such as P
317, eluxadoline and biphalin MOP and DOP receptor ligands in preclinical and
clinical trials.
PMID- 27494161
TI - Congenital Cyst of the Umbilical Cord.
AB - Umbilical cord cysts warrant evaluation for structural defects and chromosomal
anomalies such as trisomy 18, depending on the type of cyst. The appearance of an
enlarged or "gigantic" cord has particular association with a patent urachus,
often requiring operative exploration to repair the associated urachal remnant.
We describe the unusual case of an umbilical cord cyst-measuring 9 cm in maximal
diameter and comprising histopathological features of an urachalcyst-presenting
in a healthy ex-36 week newborn with no associated anomalies.
PMID- 27494164
TI - Transforming Ni9Te6 from Electron Donor to Acceptor via Ligand Exchange.
AB - The ability to donate or accept charge is a fundamental property of a chemical
species. This property is typically rooted in the valence electron count and may
be determined from the ionization potential and electron affinity. First
principles theoretical studies have been carried out to show that a cluster may
be transformed from a donor to an acceptor by changing only the ligand. Our
studies on a chalcogenide Ni9Te6 cluster show that the ionization potential and
electron affinity undergo substantial changes as the attachment of phosphine PH3
decreases the ionization potential to be less than that of sodium, whereas the
attachment of PCl3 or CO increases the adiabatic electron affinity to be greater
than iodine. The ligands change the electronic properties by creating a coulomb
well that can shift the electronic spectrum. Studies on Co9Te6(CO)8 clusters show
agreement with experiment and demonstrate that the ideas developed here are
applicable to a wider group of clusters.
PMID- 27494163
TI - Post-marketing safety surveillance conducted in Korea (2008-2013) following the
introduction of the rotavirus vaccine, RIX4414 (RotarixTM).
AB - PURPOSE: According to regulations from the Ministry of Food and Drug Safety in
Korea, additional safety information on the use of RotarixTM vaccine (RIX4414;
GSK, Belgium) in >=3000 evaluable Korean infants was required following vaccine
registration. In order to comply with these regulations, we conducted a 6-year
open, non-comparative, multicenter post-marketing surveillance (NCT00750893).
METHODS: During this time, the original lyophilized vaccine formulation of
RIX4414 was replaced by a liquid formulation. Healthy infants aged >=6 weeks were
enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of
>=4 weeks. The overall incidence of adverse events (AEs) (expected and
unexpected) was then assessed for up to 30 days along with the incidence of
serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose
causality to the drug could not be ruled out) were identified. RESULTS: A total
of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE
was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen
expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5%
infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was
upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects,
none were related to vaccination. CONCLUSIONS: We conclude that this 6-year
surveillance showed both formulations of RIX4414 to have acceptable safety
profiles when administered to Korean infants according to local prescribing
recommendations and current clinical practice.
PMID- 27494165
TI - 4, 5-Dihydrooxazole-pyrazoline hybrids: Synthesis and their evaluation as
potential antimalarial agents.
AB - A new series of oxazoline-pyrazoline hybrids (4a-p) were synthesized by
condensation reaction of substituted oxazoline based chalcones (3a-m) and
substituted hydrazines in methanol. Some of the compounds exhibited promising in
vitro antimalarial activity for chloroquine sensitive CQ(S) (3D7) strain and
chloroquine resistant CQ(R) (RKL9) strain. The most potent analogue 4i (IC50
0.322 MUg/ml) exhibited significant in vivo antimalarial potential against
Plasmodium berghei mouse model. The stable complex of 4i with hematin (1:1
stoichiometry) suggests that heme may be one possible target for these hybrid
compounds. The study has revealed potential of title compounds as lead for the
development of antimalarial agents.
PMID- 27494162
TI - The PI3K pathway in B cell metabolism.
AB - B cell growth and proliferation is tightly regulated by signaling through the B
cell receptor and by other membrane bound receptors responding to different
cytokines. The PI3K signaling pathway has been shown to play a crucial role in B
cell activation, differentiation and survival. Activated B cells undergo
metabolic reprograming in response to changing energetic and biosynthetic
demands. B cells also need to be able to coordinate metabolic activity and
proliferation with nutrient availability. The PI3K signaling network has been
implicated in regulating nutrient acquisition, utilization and biosynthesis, thus
integrating receptor-mediated signaling with cell metabolism. In this review, we
discuss the current knowledge about metabolic changes induced in activated B
cells, strategies to adapt to metabolic stress and the role of PI3K signaling in
these processes.
PMID- 27494166
TI - Biological importance of structurally diversified chromenes.
AB - Compounds incorporating the chromene scaffold are largely present in natural
products and display a wide variety of biological activities. Their low toxicity
combined to the broad pharmacological properties have inspired medicinal chemists
in the search for new therapeutic agents. This review covers the literature
between 1993 and on the biological activity of 2H- and 4H-chromenes, both from
natural and synthetic origin. Includes a section that identifies a selection of
chromene-based natural products, followed by recent literature on bioactive
natural chromenes and the corresponding source, covering plants and fruits.
Synthetic chromenes are equally important and a separate section addresses the
use of these derivatives as new leads for drug discovery. Different biological
targets were identified, namely those associated with anticancer, antimicrobial,
anti-inflammatory, antithrombotic and antipsychotic activities.
PMID- 27494167
TI - Synthesis, antimicrobial activity and advances in structure-activity
relationships (SARs) of novel tri-substituted thiazole derivatives.
AB - Trisubstituted thiazoles were synthesized and studied for their antimicrobial
activity and supported by theoretical calculations. In addition, MIC, MBC and MFC
were also tested. Moreover, the present study was analyzed to scrutinize
comprehensive structure-activity relationships. In fact, LUMO orbital energy and
orbital orientation was reliable to explain their antibacterial and antifungal
assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound
showed higher antimicrobial activity and low MIC value due to highest LUMO
energy.
PMID- 27494168
TI - Design, synthesis, and structure-activity relationship studies of benzothiazole
derivatives as antifungal agents.
AB - A series of compounds with benzothiazole and amide-imidazole scaffolds were
designed and synthesized to combat the increasing incidence of drug-resistant
fungal infections. The antifungal activity of these compounds was evaluated in
vitro, and their structure-activity relationships (SARs) were evaluated. The
synthesized compounds showed excellent inhibitory activity against Candida
albicans and Cryptococcus neoformans. The most potent compounds 14o, 14p, and 14r
exhibited potent activity, with minimum inhibitory concentration (MIC) values in
the range of 0.125-2 MUg/mL. Preliminary mechanism studies revealed that the
compound 14p might act by inhibiting the CYP51 of Candida albicans. The SARs and
binding mode established in this study are useful for further lead optimization.
PMID- 27494170
TI - Impact of early mobilization and rehabilitation on global functional outcome one
year after aneurysmal subarachnoid hemorrhage.
AB - OBJECTIVE: To assess the impact of early mobilization and rehabilitation on
global functional outcome one year after aneurysmal subarachnoid haemorrhage.
METHODS: Prospective, controlled, interventional study comprising patients
managed in the neuro-intermediate ward following repair of a ruptured
intracranial aneurysm. Patients in the Control group (n = 76) received standard
treatment, whereas those in the Early Rehab group (n = 92) in addition underwent
early mobilization and rehabilitation. Demographic, clinical and intervention
data were registered. Global functional outcome was assessed using the modified
Rankin Scale and the Glasgow Outcome Scale Extended. RESULTS: The 2 groups were
similar in their demographic and clinical characteristics. Early Rehab group
patients were mobilized more quickly (p < 0.001), median 1.4 days (range 0-23
days) after aneurysm repair. After 1 year, 47% of the patients had made a good
recovery, whereas 6.5% had died. Regression analysis did not reveal any
significant effect of early rehabilitation on functional outcome. However, in
poor-grade patients, early rehabilitation more than doubled the chance of a
favourable outcome (adjusted odds ratio = 2.33; confidence interval 1.04-5.2, p =
0.039). CONCLUSION: Early mobilization and rehabilitation probably increases the
chance of a good functional outcome in poor-grade aneurysmal subarachnoid
haemorrhage patients.
PMID- 27494169
TI - Recovery Estimation of Dried Foodborne Pathogens Is Directly Related to
Rehydration Kinetics.
AB - Drying is a common process which is used to preserve food products and
technological microorganisms, but which is deleterious for the cells. The aim of
this study is to differentiate the effects of drying alone from the effects of
the successive and necessary rehydration. Rehydration of dried bacteria is a
critical step already studied in starter culture but not for different kinetics
and not for pathogens. In the present study, the influence of rehydration
kinetics was investigated for three foodborne pathogens involved in neonatal
diseases caused by the consumption of rehydrated milk powder: Salmonella enterica
subsp. enterica serovar Typhimurium, Salmonella enterica subsp. enterica serovar
Senftenberg and Cronobacter sakazakii. Bacteria were dried in controlled relative
humidity atmospheres and then rehydrated using different methods. Our results
showed that the survival of the three pathogens was strongly related to
rehydration kinetics. Consequently, rehydration is an important step to consider
during food safety assessment or during studies of dried foodborne pathogens.
Also, it has to be considered with more attention in consumers' homes during the
preparation of food, like powdered infant formula, to avoid pathogens recovery.
PMID- 27494171
TI - A Comparison Study of Single-Echo Susceptibility Weighted Imaging and Combined
Multi-Echo Susceptibility Weighted Imaging in Visualizing Asymmetric Medullary
Veins in Stroke Patients.
AB - BACKGROUND: Asymmetric medullary veins (AMV) are frequently observed in stroke
patients and single-echo susceptibility weighted imaging (SWIs) is the main
technique in detecting AMV. Our study aimed to investigate which echo time (TE)
on single-echo susceptibility is the optimal echo for visualizing AMV and to
compare the ability in detecting AMV in stroke patients between SWIs and multi
echo susceptibility weighted imaging (SWIc). MATERIALS AND METHODS: Twenty
patients with middle cerebral artery stroke were included. SWI was acquired by
using a multi-echo gradient-echo sequence with six echoes ranging from 5 ms to
35.240 ms. Three different echoes of SWIs including SWIs1 (TE = 23.144 ms), SWIs2
(TE = 29.192 ms) and SWIs3 (TE = 35.240 ms) were reconstructed. SWIc was averaged
using the three echoes of SWIs. Image quality and venous contrast of medullary
veins were compared between SWIs and SWIc using peak signal-to-noise ratio
(PSNR), mean opinion score (MOS), contrast-to-noise ratio (CNR) and signal-to
noise ratio (SNR). The presence of AMV was evaluated in each SWIs (1-3) and SWIc.
RESULTS: SWIs2 had the highest PSNR, MOS and CNR and SWIs1 had the highest SNR
among three different echoes of SWIs. No significant difference was found in SNR
between SWIs1 and SWIs2. PSNR, MOS and CNR in SWIc were significantly increased
by 27.9%, 28.2% and 17.2% compared with SWIs2 and SNR in SWIc was significantly
increased by 32.4% compared with SWIs1. 55% of patients with AMV were detected in
SWIs2, SWIs3 and SWIc, while 50% AMV were found in SWIs1. CONCLUSIONS: SWIs using
TE around 29ms was optimal in visualizing AMV. SWIc could improve image quality
and venous contrast, but was equal to SWIs using a relative long TE in evaluating
AMV. These results provide the technique basis for further research of AMV in
stroke.
PMID- 27494173
TI - Potential Intervention of alpha- Lipoic Acid and Carnitine on Insulin Sensitivity
and Anti-Inflammatory Cytokines Levels in Fructose-Fed Rats, a Model of Metabolic
Syndrome.
AB - The objective of this work was to evaluate the beneficial effect of alpha-lipoic
acid (ALA) and L-carnitine (CAR) on insulin sensitivity and anti-inflammatory
markers in animal model of metabolic syndrome (MS), high fructose (HF)-fed rats.
Forty male rats were randomly divided into four groups (n = 10). Group 1(control
rats, G1), animals were allowed to drink 0.2% gum acacia (GA, p.o) and were fed a
modified diet containing 65% cornstarch. The remaining rats were induced MS by
feeding the same diet + free access to 10% fructose (w/v) in 0.2% GA (HF, MS) for
4 weeks. After 4 weeks of HF feeding, the rats were further divided into three
subgroups; G2: HF (MS) in 0.2% GA, G3: HF (MS)+CAR (200 mg/kg/day) in 0.2% GA and
G4: HF (MS)+ALA (200 mg/kg/day) in 0.2% GA, respectively. All ingredients were
administered orally by guava daily for four weeks. A significant increase in
serum glucose, insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA
IR) levels was observed after four weeks of HF feeding compared to control rats.
Administration of ALA and CAR reversed the increase of the mentioned parameters.
In HF rats, the increase of serum triglycerides (TG), total cholesterol (TC), and
low-density lipoprotein cholesterol (LDL-C) levels were significantly lowered,
while the reduction of the serum high-density lipoprotein cholesterol (HDL-C) was
alleviated after administration of CAR and ALA. The reduction of the serum
adiponectin level was significantly increased after administration of CAR and
ALA. These data suggested that CAR and/or ALA had a beneficial role in the
prevention of MS associated with development of type 2 diabetes.
PMID- 27494172
TI - Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar.
AB - Rhythmic incremental growth lines and the presence of melatonin receptors were
discovered in tooth enamel, suggesting possible role of circadian rhythm. We
therefore hypothesized that circadian rhythm may regulate enamel formation
through melatonin receptors. To test this hypothesis, we examined expression of
melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation,
during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we
found that mRNA and protein levels of both MTs and AMELX in normal mandibular
first molar tooth germs increased gradually after birth, peaked at 3 or 4 day
postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry
was significantly delayed in neonatal mice raised in all-dark or all-light
environment as well as the enamel development. Furthermore, development of tooth
enamel was also delayed showing significant immature histology in those animals,
especially for newborn mice raised in all daylight condition. Interestingly,
disruption in circadian rhythm in pregnant mice also resulted in delayed enamel
development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT
in pregnant mice caused underexpression of MTs and AMELX associated with long
lasting deficiency in baby enamel tissue. Electromicroscopic evidence
demonstrated increased necrosis and poor enamel mineralization in ameloblasts.
The above results suggest that circadian rhythm is important for normal enamel
development at both pre- and postnatal stages. Melatonin receptors were partly
responsible for the regulation.
PMID- 27494174
TI - Polyacrylamide-Polydivinylbenzene Decorated Membrane for Sundry Ionic Stabilized
Emulsions Separation via a Facile Solvothermal Method.
AB - Aiming to solve the worldwide challenge of stabilized oil-in-water emulsion
separation, a PAM-PDVB decorated nylon membrane is fabricated via a facile
solvothermal route in our group. The main composition is PAM, while the PDVB
plays a role as cross-linker in order to improve the interaction between the
polymer and the substrate. By the combination of the superhydrophilic and
underwater superoleophobic wettability of the PAM polymer with the micropore size
of the substrate, the as-prepared material is able to achieve the separation of
various stabilized oil-in-water emulsions including cationic type, nonionic type,
and anionic type. Compared with previous works, the emulsions used in this case
are more stable and can stay for several days. Besides, the solvothermal method
is facile, cost saving, and relatively environmentally friendly in this
experiment. Moreover, the PAM-PDVB modified membrane exhibits excellent pH
stability, recyclability, and high separation efficiency (above 99%), which can
be scaled up and used in the practical industrial field.
PMID- 27494175
TI - Sulfur and sulfur nanoparticles as potential antimicrobials: from traditional
medicine to nanomedicine.
AB - INTRODUCTION: The alarming rate of infections caused by various pathogens and
development of their resistance towards a large number of antimicrobial agents
has generated an essential need to search for novel and effective antimicrobial
agents. Metal nanoparticles such as silver have been widely used and accepted as
strong antimicrobial agents, but considering the cost effectiveness and
significant bioactivities, researchers are looking to utilize sulfur
nanoparticles as an effective alternative to silver nanoparticles. AREAS COVERED:
This review has been focused on different approaches for the synthesis of sulfur
nanoparticles, their broad spectrum bioactivities and possible mechanisms
involved in their bioactivities. Expert commentary: Sulfur nanoparticles are
reported to possess broad spectrum antimicrobial activity, and hence can be used
to treat microbial infections and potentially tackle the problem of antibiotic
resistance. Thus, in the future, sulfur nanoparticles can be used as an
effective, non-toxic and economically viable alternative to other precious metal
nanoparticles.
PMID- 27494176
TI - A green tea-containing starch confection increases plasma catechins without
protecting against postprandial impairments in vascular function in normoglycemic
adults.
AB - Postprandial hyperglycemia (PPH) increases cardiovascular disease risk regardless
of glucose intolerance by transiently impairing vascular endothelial function
(VEF) by limiting nitric oxide bioavailability in an oxidative stress-dependent
manner. Preclinical studies show that green tea catechins attenuate PPH by
inhibiting starch digestion. We hypothesized that a starch-based confection
containing catechin-rich green tea extract (GTE) would limit PPH-mediated
impairments in VEF in normoglycemic adults. We formulated a unique GTE confection
and then conducted a double-blind, randomized, controlled, crossover study in
healthy men (n = 15; 25.3 +/- 1.0 years; 22.4 +/- 1.8 kg m(-2)) in which they
ingested starch confections (50 g carbohydrate) formulated with or without GTE (1
g) prior to evaluating sensory characteristics of confections and plasma glucose,
biomarkers of lipid peroxidation and nitric oxide homeostasis, and brachial
artery flow-mediated dilation (FMD) at 30 min intervals for 3 h. Sensory
evaluation of confections indicated acceptable consumer appeal and an inability
to distinguish between confections regardless of GTE. Plasma catechins
concentrations increased following ingestion of the GTE confection. However,
plasma glucose peaked at 60 min (P < 0.05) following confection ingestion and was
unaffected throughout the postprandial period by the GTE confection (P > 0.05).
FMD was significantly decreased only at 60 min regardless of confections
containing GTE. Also at 60 min, both confections similarly increased plasma
malondialdehyde while decreasing arginine and increasing asymmetric
dimethylarginine/arginine. The successfully formulated GTE-containing confection
effectively delivered catechins, but without mitigating PPH-mediated impairments
in VEF in association with oxidative stress that likely limits nitric oxide
bioavailability.
PMID- 27494177
TI - Patient education and basic body awareness therapy in hip osteoarthritis - a
qualitative study of patients' movement learning experiences.
AB - BACKGROUND: Osteoarthritis (OA) is associated with pain, dysfunction and reduced
quality of life. Patient education (PE) followed by 12 weekly sessions of Basic
Body Awareness Therapy (BBAT) was offered to patients with hip OA, aiming to
strengthen their ability to move and act functionally in daily life. AIM: To
explore how patients described their experiences and outcome from participating
in PE and BBAT. METHOD: Individual, semi-structured interviews with five
patients, aged 52-78 years, were performed after PE and BBAT at four and ten
months. Interview data were analyzed by systematic text condensation. RESULTS:
Three main themes emerged. "Becoming motivated and involved" reflected
experiences of encouragement and support from information given and communication
with group members. In "Movement awareness learning" patients described becoming
aware of and improving functional movement, alleviating symptoms and increasing
daily functioning. "Movement and disease in a long-term perspective" reflected
patients experience of increased self-awareness and taking better care of
themselves at 10 months after baseline. Practicing basic movement principles,
they felt empowered to handle daily life challenges in more functional and energy
economical ways. CONCLUSION: PE followed by BBAT in groups may be beneficial to
patients with hip OA, and provide lasting benefits regarding daily life function.
Implications for Rehabilitation Insight into disease process and relationship to
functional movement gained through patient education may empower patients with
hip osteoarthritis in management of daily life Movement awareness and exploration
of movement quality using principles from Basic Body Awareness Therapy was found
to support patients in finding resources for functional movement, implemented in
daily actions Movement strategies characterized by adjustment rather than force
was experienced by the patients to support their general functioning, despite of
prevailing hip pain Implementing group therapeutic factors (Yalom) in
physiotherapy was found to strengthen patients' motivation and belief in
functional improvement.
PMID- 27494178
TI - Flow-Based Network Analysis of the Caenorhabditis elegans Connectome.
AB - We exploit flow propagation on the directed neuronal network of the nematode C.
elegans to reveal dynamically relevant features of its connectome. We find flow
based groupings of neurons at different levels of granularity, which we relate to
functional and anatomical constituents of its nervous system. A systematic in
silico evaluation of the full set of single and double neuron ablations is used
to identify deletions that induce the most severe disruptions of the multi
resolution flow structure. Such ablations are linked to functionally relevant
neurons, and suggest potential candidates for further in vivo investigation. In
addition, we use the directional patterns of incoming and outgoing network flows
at all scales to identify flow profiles for the neurons in the connectome,
without pre-imposing a priori categories. The four flow roles identified are
linked to signal propagation motivated by biological input-response scenarios.
PMID- 27494179
TI - Prevalence of High-Risk Human Papillomavirus (HR-HPV) Genotypes and Multiple
Infections in Cervical Abnormalities from Northern Xinjiang, China.
AB - Multiple human papillomavirus (HPV) genotypes often coexist within the cervical
epithelia and are frequently detected together in various grades of the cervical
neoplasia. To date, only a few reports exist on multiple HPV infections of HPV in
Xinjiang Uygur Autonomous Region (XUAR). In the present study, we investigated
the prevalence of High-Risk HPV (HR-HPV) genotypes and multiple infections.
Cervical cytology samples were collected from 428 women who presented cervical
abnormalities. Genotyping of HPV was performed by polymerase chain reaction
sequencing based typing (PCR-SBT) using consensus primers and specific primers.
Of them, 166 samples were positive for HPV according to PCR results using the
consensus primers. These samples contained cervical abnormalities enriched with
inflammation (n = 107), cervical intraepithelial neoplasia (CIN) I (n = 19),
CINII-III (n = 9) and cervical cancer (n = 31). Of the 166 HPV positive samples
as determined by PCR analysis, 151 were further typed by PCR-SBT using 19 pairs
of genotype-specific primers. Using this method, 17 different HR-HPV genotypes
were identified. The most frequently observed HPV genotypes were HPV16 (44.0%,
73/166), 53 (28.9%, 48/166), 52 (25.3%, 42/166), 58 (22.3%, 37/166) and 35
(17.5%, 29/166). The proportions of single and multiple infections in the HPV
positive specimens were 34.9% and 65.1%, respectively. Multiple HPV types were
most prevalent in the inflammatory state (63.0%), followed by cervical cancer
(24.1%), CINI (11.1%), and CINII-III (1.9%). The results of our data analyses
suggested that i) multiple HPV infection is not necessarily correlated with the
severity of cervical abnormalities; and ii) among the multiple HPV infections,
double infections combined with HPV16 is the most common. In addition, L1 full
length sequences of the top five high-risk HPV genotypes were amplified and
sequenced. According to the L1 sequence of the epidemic genotypes that were
amplified, we found that these genotypes contained the sequence point mutation,
and that some of these genotypes further showed amino acid modifications. These
results provide a basis for the construction of a polyvalent vaccine that is
suitable for use in the XUAR, even in economically challenged communities located
in China.
PMID- 27494180
TI - Moderate-Heavy Alcohol Consumption Lifestyle in Older Adults Is Associated with
Altered Central Executive Network Community Structure during Cognitive Task.
AB - Older adults today consume more alcohol than previous generations, the majority
being social drinkers. The effects of heavy alcohol use on brain functioning
closely resemble age-related changes, but it is not known if moderate-heavy
alcohol consumption intensifies brain aging. Whether a lifestyle of moderate
heavy alcohol use in older adults increased age-related brain changes was
examined. Forty-one older adults (65-80 years) that consumed light (< 2
drinks/week and >= 1 drink/month, n = 20) or moderate-heavy (7-21 drinks/week,
non-bingers, n = 21) amounts of alcohol were enrolled. Twenty-two young adults
(24-35 years) were also enrolled (light, n = 11 and moderate-heavy, n = 11).
Functional brain networks based on magnetic resonance imaging data were generated
for resting state and during a working memory task. Whole-brain, Central
Executive Network (CEN), and Default Mode Network (DMN) connectivity were
assessed in light and moderate-heavy alcohol consuming older adults with
comparisons to young adults. The older adults had significantly lower whole brain
connectivity (global efficiency) and lower regional connectivity (community
structure) in the CEN during task and in the DMN at rest. Moderate-heavy older
drinkers did not exhibit whole brain connectivity differences compared to the low
drinkers. However, decreased CEN connectivity was observed during the task. There
were no differences in the DMN connectivity between drinking groups. Taken
together, a lifestyle including moderate-heavy alcohol consumption may be
associated with further decreases in brain network connectivity within task
related networks in older adults. Further research is required to determine if
this decrease is compensatory or an early sign of decline.
PMID- 27494181
TI - Identification of KCa3.1 Channel as a Novel Regulator of Oxidative
Phosphorylation in a Subset of Pancreatic Carcinoma Cell Lines.
AB - Pancreatic ductal adenocarcinoma (PDAC) represents the most common form of
pancreatic cancer with rising incidence in developing countries and overall 5
year survival rates of less than 5%. The most frequent mutations in PDAC are gain
of-function mutations in KRAS as well as loss-of-function mutations in p53. Both
mutations have severe impacts on the metabolism of tumor cells. Many of these
metabolic changes are mediated by transporters or channels that regulate the
exchange of metabolites and ions between the intracellular compartment and the
tumor microenvironment. In the study presented here, our goal was to identify
novel transporters or channels that regulate oxidative phosphorylation (OxPhos)
in PDAC in order to characterize novel potential drug targets for the treatment
of these cancers. We set up a Seahorse Analyzer XF based siRNA screen and
identified previously described as well as novel regulators of OxPhos. The siRNA
that resulted in the greatest change in cellular oxygen consumption was targeting
the KCNN4 gene, which encodes for the Ca2+-sensitive K+ channel KCa3.1. This
channel has not previously been reported to regulate OxPhos. Knock-down
experiments as well as the use of a small molecule inhibitor confirmed its role
in regulating oxygen consumption, ATP production and cellular proliferation.
Furthermore, PDAC cell lines sensitive to KCa3.1 inhibition were shown to express
the channel protein in the plasma membrane as well as in the mitochondria. These
differences in the localization of KCa3.1 channels as well as differences in the
regulation of cellular metabolism might offer opportunities for targeted therapy
in subsets of PDAC.
PMID- 27494182
TI - Diurnal Variations of Human Circulating Cell-Free Micro-RNA.
AB - A 24-hour light and dark cycle-dependent rhythmicity pervades physiological
processes in virtually all living organisms including humans. These regular
oscillations are caused by external cues to endogenous, independent biological
time-keeping systems (clocks). The rhythm is reflected by gene expression that
varies in a circadian and specific fashion in different organs and tissues and is
regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This
leads to well-documented oscillations of specific electrolytes, hormones,
metabolites, and plasma proteins in blood samples. An emerging, important class
of gene regulators is short single-stranded RNA (micro-RNA, miRNA) that
interferes post-transcriptionally with gene expression and thus may play a role
in the circadian variation of gene expression. MiRNAs are promising biomarkers by
virtue of their disease-specific tissue expression and because of their presence
as stable entities in the circulation. However, no studies have addressed the
putative circadian rhythmicity of circulating, cell-free miRNAs. This question is
important both for using miRNAs as biological markers and for clues to miRNA
function in the regulation of circadian gene expression. Here, we investigate 92
miRNAs in plasma samples from 24 young male, healthy volunteers repeatedly
sampled 9 times during a 24-hour stay in a regulated environment. We demonstrate
that a third (26/79) of the measurable plasma miRNAs (using RT-qPCR on a
microfluidic system) exhibit a rhythmic behavior and are distributed in two main
phase patterns. Some of these miRNAs weakly target known clock genes and many
have strong targets in intracellular MAPK signaling pathways. These novel
findings highlight the importance of considering bio-oscillations in miRNA
biomarker studies and suggest the further study of a set of specific circulating
miRNAs in the regulation and functioning of biological clocks.
PMID- 27494183
TI - A Secondary Antibody-Detecting Molecular Weight Marker with Mouse and Rabbit IgG
Fc Linear Epitopes for Western Blot Analysis.
AB - Molecular weight markers that can tolerate denaturing conditions and be auto
detected by secondary antibodies offer great efficacy and convenience for Western
Blotting. Here, we describe M&R LE protein markers which contain linear epitopes
derived from the heavy chain constant regions of mouse and rabbit immunoglobulin
G (IgG Fc LE). These markers can be directly recognized and stained by a wide
range of anti-mouse and anti-rabbit secondary antibodies. We selected three mouse
(M1, M2 and M3) linear IgG1 and three rabbit (R1, R2 and R3) linear IgG heavy
chain epitope candidates based on their respective crystal structures. Western
blot analysis indicated that M2 and R2 linear epitopes are effectively recognized
by anti-mouse and anti-rabbit secondary antibodies, respectively. We fused the M2
and R2 epitopes (M&R LE) and incorporated the polypeptide in a range of 15-120
kDa auto-detecting markers (M&R LE protein marker). The M&R LE protein marker can
be auto-detected by anti-mouse and anti-rabbit IgG secondary antibodies in
standard immunoblots. Linear regression analysis of the M&R LE protein marker
plotted as gel mobility versus the log of the marker molecular weights revealed
good linearity with a correlation coefficient R2 value of 0.9965, indicating that
the M&R LE protein marker displays high accuracy for determining protein
molecular weights. This accurate, regular and auto-detected M&R LE protein marker
may provide a simple, efficient and economical tool for protein analysis.
PMID- 27494184
TI - Neuronal mechanisms of motor learning are age dependent.
AB - There is controversy whether age-related neuroanatomical and neurophysiological
changes in the central nervous system affect healthy old adults' abilities to
acquire and retain motor skills. We examined the effects of age on motor skill
acquisition and retention and potential underlying mechanisms by measuring
corticospinal and intracortical excitability, using transcranial magnetic
stimulation. Healthy young (n = 24, 22 years) and old (n = 22, 71 years) adults
practiced a wrist flexion-extention visuomotor task or only watched the templates
as an attentional control for 20 minutes. Old compared with young adults
performed less well at baseline. Although the absolute magnitude of skill
acquisition and retention was similar in the 2 age groups (age * intervention *
time, p = 0.425), a comparison of baseline-similar age sub-groups revealed
impaired skill acquisition but not retention in old versus young. Furthermore,
the neuronal mechanisms differed as revealed by an opposite direction of
associations in the age-groups between relative skill acquisition and
intracortical facilitation during the task, and opposite changes during skill
retention in corticospinal excitability at rest and during the task and
intracortical inhibition during the task.
PMID- 27494186
TI - Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals
Pandemic Vaccine Candidates.
AB - Recently, an avian influenza virus, H5NX subclade 2.3.4.4, emerged and spread to
North America. This subclade has frequently reassorted, leading to multiple novel
viruses capable of human infection. Four cases of human infections, three leading
to death, have already occurred. Existing vaccine strains do not protect against
these new viruses, raising a need to identify new vaccine candidate strains. We
have developed a novel sequence-based mapping (SBM) tool capable of visualizing
complex protein sequence data sets using a single intuitive map. We applied SBM
on the complete set of avian H5 viruses in order to better understand
hemagglutinin protein variance amongst H5 viruses and identify any patterns
associated with this variation. The analysis successfully identified the original
reassortments that lead to the emergence of this new subclade of H5 viruses, as
well as their known unusual ability to re-assort among neuraminidase subtypes. In
addition, our analysis revealed distinct clusters of 2.3.4.4 variants that would
not be covered by existing strains in the H5 vaccine stockpile. The results
suggest that our method may be useful for pandemic candidate vaccine virus
selection.
PMID- 27494185
TI - MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII
Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent
Serotype Specific Sub-populations and Distant Ancestors.
AB - The emerging pathogen Cryptococcus gattii causes life-threatening disease in
immunocompetent and immunocompromised hosts. Of the four major molecular types
(VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in
otherwise healthy individuals, prompting a need to investigate its population
genetic structure to understand if there are potential genotype-dependent
characteristics in its epidemiology, environmental niche(s), host range and
clinical features of disease. Multilocus sequence typing (MLST) of 122 clinical,
environmental and veterinary C. gattii VGIII isolates from Australia, Colombia,
Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela, and whole genome
sequencing (WGS) of 60 isolates representing all established MLST types
identified four divergent sub-populations. The majority of the isolates belong to
two main clades, corresponding either to serotype B or C, indicating an ongoing
species evolution. Both major clades included clinical, environmental and
veterinary isolates. The C. gattii VGIII population was genetically highly
diverse, with minor differences between countries, isolation source, serotype and
mating type. Little to no recombination was found between the two major groups,
serotype B and C, at the whole and mitochondrial genome level. C. gattii VGIII is
widespread in the Americas, with sporadic cases occurring elsewhere, WGS revealed
Mexico and USA as a likely origin of the serotype B VGIII population and Colombia
as a possible origin of the serotype C VGIII population. Serotype B isolates are
more virulent than serotype C isolates in a murine model of infection, causing
predominantly pulmonary cryptococcosis. No specific link between genotype and
virulence was observed. Antifungal susceptibility testing against six antifungal
drugs revealed that serotype B isolates are more susceptible to azoles than
serotype C isolates, highlighting the importance of strain typing to guide
effective treatment to improve the disease outcome.
PMID- 27494187
TI - Differential Expression of FosB Proteins and Potential Target Genes in Select
Brain Regions of Addiction and Depression Patients.
AB - Chronic exposure to stress or drugs of abuse has been linked to altered gene
expression throughout the body, and changes in gene expression in discrete brain
regions are thought to underlie many psychiatric diseases, including major
depressive disorder and drug addiction. Preclinical models of these disorders
have provided evidence for mechanisms of this altered gene expression, including
transcription factors, but evidence supporting a role for these factors in human
patients has been slow to emerge. The transcription factor DeltaFosB is induced
in the prefrontal cortex (PFC) and hippocampus (HPC) of rodents in response to
stress or cocaine, and its expression in these regions is thought to regulate
their "top down" control of reward circuitry, including the nucleus accumbens
(NAc). Here, we use biochemistry to examine the expression of the FosB family of
transcription factors and their potential gene targets in PFC and HPC postmortem
samples from depressed patients and cocaine addicts. We demonstrate that
DeltaFosB and other FosB isoforms are downregulated in the HPC but not the PFC in
the brains of both depressed and addicted individuals. Further, we show that
potential DeltaFosB transcriptional targets, including GluA2, are also
downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the
first evidence of FosB gene expression in human HPC and PFC in these psychiatric
disorders, and in light of recent findings demonstrating the critical role of HPC
DeltaFosB in rodent models of learning and memory, these data suggest that
reduced DeltaFosB in HPC could potentially underlie cognitive deficits
accompanying chronic cocaine abuse or depression.
PMID- 27494188
TI - Interannual abundance changes of gelatinous carnivore zooplankton unveil climate
driven hydrographic variations in the Iberian Peninsula, Portugal.
AB - The persistent massive blooms of gelatinous zooplankton recorded during recent
decades may be indicative of marine ecosystem changes. In this study, we
investigated the potential influence of the North Atlantic climate (NAO)
variability on decadal abundance changes of gelatinous carnivore zooplankton in
the Mondego estuary, Portugal, over the period 2003-2013. During the 11-year
study, the community of gelatinous carnivores encompassed a larger diversity of
hydromedusae than siphonophores; the former dominated by Obelia spp., Lizzia
blondina, Clythia hemisphaerica, Liriope tetraphylla and Solmaris corona, while
the latter dominated by Muggiaea atlantica. Gelatinous carnivore zooplankton
displayed marked interannual variability and mounting species richness over the
period examined. Their pattern of abundance shifted towards larger abundances ca.
2007 and significant phenological changes. The latter included a shift in the
mean annual pattern (from unimodal to bimodal peak, prior and after 2007
respectively) and an earlier timing of the first annual peak concurrent with
enhanced temperatures. These changes were concurrent with the climate-driven
environmental variability mainly controlled by the NAO, which displayed larger
variance after 2007 along with an enhanced upwelling activity. Structural
equation modelling allowed depicting cascading effects derived from the NAO
influence on regional climate and upwelling variability further shaping water
temperature. Such cascading effect percolated the structure and dynamics of the
community of gelatinous carnivore zooplankton in the Mondego estuary.
PMID- 27494189
TI - Digestive selection underlies differential utilization of phytoplankton and
sedimentary organics by infaunal bivalves: Experiments with cockles (Cerastoderma
edule) using cross-labelled mixed diets.
AB - Differential utilization of phytoplankton and detrital particles present in
natural sediments of mud-flats was studied in a series of experiments performed
on the infaunal bivalve Cerastoderma edule. In order to assess digestive
selection, parameters of food processing (organic ingestion rate: OIR, gross
absorption efficiency: GAE and gut passage time: GPT) were recorded for each
organic component in different combinations of food particles radio-labelled with
(14)C. Experimental design included the use of both labelled diets of a sole
organic component and cross-labelled diets; i.e., mixed suspensions presenting
alternatively labelled one of the various components tested: phytoplankton cells,
sedimentary organic particles and particulate detritus from vascular salt-marsh
plants. Preferential absorption of phytoplankton was accounted for by absorption
efficiency values that were two-fold those for sedimentary detritus when recorded
with mixed diets of both organic components. Two factors contributed to this
difference: a) higher digestibility of microalgae, measured as the ratio of GAE
to GPT, and b) faster gut passage of detrital particles that results from
digestive selection likely involving the preferential incorporation of
phytoplankton into the digestive gland. However, when diets based on a sole
organic component (either phytoplankton or detritus) were compared, larger GPT
were recorded for detrital particles that enabled improving GAE of this rather
refractory food. Overall results of these experiments are consistent with most
studies in trophic ecology based on stable isotopes enrichment, concerning both
the diversity of trophic sources used by marine bivalves and its preferential
utilization of phytoplankton over phyto-detritus.
PMID- 27494190
TI - Comprehensive Emerging Chemical Discovery: Novel Polyfluorinated Compounds in
Lake Michigan Trout.
AB - A versatile screening algorithm capable of efficiently searching liquid
chromatographic/mass spectrometric data for unknown compounds has been developed
using a combination of open source and generic computing software packages. The
script was used to search for select novel polyfluorinated contaminants in Great
Lakes fish. However, the framework is applicable whenever full-scan, high
resolution mass spectral and chromatographic data are collected. Target compound
classes are defined and a matrix of candidates is generated that includes mass
spectral profiles and likely fragmentation pathways. The initial calibration was
performed using a standard solution of known linear perfluoroalkyl acids. Once
validated, Lake Michigan trout data files were analyzed for polyfluoroalkyl acids
using the algorithm referencing 3570 possible compounds including C4-C10
perfluoro- and polyfluoroalkyl, polyfluorochloroalkyl acids and sulfonates, and
potential ether forms. The results suggest the presence of 30 polyfluorinated
chemical formulas which have not been previously reported in the literature. The
identified candidates included mono- to hexafluoroalkyl carboxylic acids, mono-
and trifluoroalkyl carboxylic acid ethers, and novel polyfluoroalkyl sulfonates.
Candidate species identified in lake trout were qualified using theoretical
isotopic profile matching, characteristic fragmentation patterns based on known
linear perfluoroalkyl acid (PFAA) fragmentation, and retention time
reproducibility among replicate extractions and injections. In addition, the
relative retention times of multiple species within a compound class were
compared based on theoretical octanol-water partition coefficients.
PMID- 27494191
TI - Local Optima in Mixture Modeling.
AB - It is common knowledge that mixture models are prone to arrive at locally optimal
solutions. Typically, researchers are directed to utilize several random
initializations to ensure that the resulting solution is adequate. However, it is
unknown what factors contribute to a large number of local optima and whether
these coincide with the factors that reduce the accuracy of a mixture model. A
real-data illustration and a series of simulations are presented that examine the
effect of a variety of data structures on the propensity of local optima and the
classification quality of the resulting solution. We show that there is a
moderately strong relationship between a solution that has a high proportion of
local optima and one that is poorly classified.
PMID- 27494192
TI - Impact of Microarray Preprocessing Techniques in Unraveling Biological Pathways.
AB - To better understand the impact of microarray preprocessing normalization
techniques on the analysis of biological pathways in the prediction of chronic
fatigue (CF) following radiation therapy, this study has compared the list of
predictive genes found using the Robust Multiarray Averaging (RMA) and the
Affymetrix MAS5 method, with the list that is obtained working with raw data
(without any preprocessing). First, we modeled the spiked-in data set where
differentially expressed genes were known and spiked-in at different known
concentrations, showing that the precisions established by different gene ranking
methods were higher than working with raw data. The results obtained from the
spiked-in experiment were extrapolated to the CF data set to run learning and
blind validation. RMA and MAS5 provided different sets of discriminatory genes
that have a higher predictive accuracy in the learning phase, but lower
predictive accuracy during the blind validation phase, suggesting that the
genetic signatures generated using both preprocessing techniques cannot be
generalizable. The pathways found using the raw data set better described what is
a priori known for the CF disease. Besides, RMA produced more reliable pathways
than MAS5. Understanding the strengths of these two preprocessing techniques in
phenotype prediction is critical for precision medicine. Particularly, this
article concludes that biological pathways might be better unraveled working with
raw expression data. Moreover, the interpretation of the predictive gene profiles
generated by RMA and MAS5 should be done with caution. This is an important
conclusion with a high translational impact that should be confirmed in other
disease data sets.
PMID- 27494194
TI - Meta-analysis of the incidence and risk of arterial and venous thromboembolic
events associated with anti-EGFR agents in non-small-cell lung cancer patients.
AB - BACKGROUND: To determine the risk of arterial and venous thromboembolic events
(ATEs and VETs) associated with anti-epidermal growth factor receptor (EGFR)
agents in non-small-cell lung cancer (NSCLC) patients. METHODS: Prospective
randomized trials evaluating therapy with or without anti-EGFR agents in NSCLC
patients. Data on VTEs and ATEs were extracted. RESULTS: A total of 8,410
patients from 12 trials were included for analysis. Anti-EGFR agents
significantly increased the risk of all-grade and high-grade VTEs (Peto OR 1.50,
95%CI 1.16-1.95, P = 0.002; Peto OR 1.73, 95%CI: 1.32-2.26, p < 0.001,
respectively), but not for all-grade and high-grade ATEs. CONCLUSION: The use of
anti-EGFR agents significantly increased the risk of all-grade and high-grade
VTEs but not for ATEs in NSCLC patients.
PMID- 27494193
TI - Techniques for the interruption of tubal patency for female sterilisation.
AB - BACKGROUND: This is an update of a review that was first published in 2002.
Female sterilisation is the most popular contraceptive method worldwide. Several
techniques exist for interrupting the patency of fallopian tubes, including
cutting and tying the tubes, damaging the tube using electric current, applying
clips or silicone rubber rings, and blocking the tubes with chemicals or tubal
inserts. OBJECTIVES: To compare the different tubal occlusion techniques in terms
of major and minor morbidity, failure rates (pregnancies), technical failures and
difficulties, and women's and surgeons' satisfaction. SEARCH METHODS: For the
original review published in 2002 we searched MEDLINE and the Cochrane Central
Register of Controlled Trials (CENTRAL). For this 2015 update, we searched
POPLINE, LILACS, PubMed and CENTRAL on 23 July 2015. We used the related articles
feature of PubMed and searched reference lists of newly identified trials.
SELECTION CRITERIA: All randomized controlled trials (RCTs) comparing different
techniques for tubal sterilisation, irrespective of the route of fallopian tube
access or the method of anaesthesia. DATA COLLECTION AND ANALYSIS: For the
original review, two review authors independently selected studies, extracted
data and assessed risk of bias. For this update, data extraction was performed by
one author (TL) and checked by another (RK). We grouped trials according to the
type of comparison evaluated. Results are reported as odds ratios (OR) or mean
differences (MD) using fixed-effect methods, unless heterogeneity was high, in
which case we used random-effects methods. MAIN RESULTS: We included 19 RCTs
involving 13,209 women. Most studies concerned interval sterilisation; three RCTs
involving 1632 women, concerned postpartum sterilisation. Comparisons included
tubal rings versus clips (six RCTs, 4232 women); partial salpingectomy versus
electrocoagulation (three RCTs, 2019 women); tubal rings versus
electrocoagulation (two RCTs, 599 women); partial salpingectomy versus clips
(four RCTs, 3627 women); clips versus electrocoagulation (two RCTs, 206 women);
and Hulka versus Filshie clips (two RCTs, 2326 women). RCTs of clips versus
electrocoagulation contributed no data to the review.One year after
sterilisation, failure rates were low (< 5/1000) for all methods.There were no
deaths reported with any method, and major morbidity related to the occlusion
technique was rare.Minor morbidity was higher with the tubal ring than the clip
(Peto OR 2.15, 95% CI 1.22 to 3.78; participants = 842; studies = 2; I2 = 0%;
high-quality evidence), as were technical failures (Peto OR 3.93, 95% CI 2.43 to
6.35; participants = 3476; studies = 3; I2 = 0%; high-quality evidence).Major
morbidity was significantly higher with the modified Pomeroy technique than
electrocoagulation (Peto OR 2.87, 95% CI 1.13 to 7.25; participants = 1905;
studies = 2; I2 = 0%; low-quality evidence), as was postoperative pain (Peto OR
3.85, 95% CI 2.91 to 5.10; participants = 1905; studies = 2; I2 = 0%; moderate
quality evidence).When tubal rings were compared with electrocoagulation,
postoperative pain was reported significantly more frequently for tubal rings (OR
3.40, 95% CI 1.17 to 9.84; participants = 596; studies = 2; I2 = 87%; low-quality
evidence).When partial salpingectomy was compared with clips, there were no major
morbidity events in either group (participants = 2198, studies = 1). The
frequency of minor morbidity was low and not significantly different between
groups (Peto OR 7.39, 95% CI 0.46 to 119.01; participants = 193; studies = 1, low
quality evidence). Although technical failure occurred more frequently with clips
(Peto OR 0.18, 95% CI 0.08 to 0.40; participants = 2198; studies = 1; moderate
quality evidence); operative time was shorter with clips than partial
salpingectomy (MD 4.26 minutes, 95% CI 3.65 to 4.86; participants = 2223; studies
= 2; I2 = 0%; high-quality evidence).We found little evidence concerning women's
or surgeon's satisfaction. No RCTs compared tubal microinserts (hysteroscopic
sterilisation) or chemical inserts (quinacrine) to other methods. AUTHORS'
CONCLUSIONS: Tubal sterilisation by partial salpingectomy, electrocoagulation, or
using clips or rings, is a safe and effective method of contraception. Failure
rates at 12 months post-sterilisation and major morbidity are rare outcomes with
any of these techniques. Minor complications and technical failures appear to be
more common with rings than clips. Electrocoagulation may be associated with less
postoperative pain than the modified Pomeroy or tubal ring methods. Further
research should include RCTs (for effectiveness) and controlled observational
studies (for adverse effects) on sterilisation by minimally-invasive methods,
i.e. tubal inserts and quinacrine.
PMID- 27494195
TI - Growth of transition metals on cerium tungstate model catalyst layers.
AB - Two model catalytic metal/oxide systems were investigated by photoelectron
spectroscopy and scanning tunneling microscopy. The mixed-oxide support was a
cerium tungstate epitaxial thin layer grown in situ on the W(1 1 0) single
crystal. Active particles consisted of palladium and platinum 3D islands
deposited on the tungstate surface at 300 K. Both metals were found to interact
weakly with the oxide support and the original chemical state of both support and
metals was mostly preserved. Electronic and morphological changes are discussed
during the metal growth and after post-annealing at temperatures up to 700 K.
Partial transition-metal coalescence and self-cleaning from the CO and carbon
impurities were observed.
PMID- 27494196
TI - Cassava traits and end-user preference: Relating traits to consumer liking,
sensory perception, and genetics.
AB - Breeding efforts have focused on improving agronomic traits of the cassava plant
however little research has been done to enhance the crop palatability. This
review investigates the links between cassava traits and end-user preference in
relation with sensory characteristics. The main trait is starch and its
composition related to the textural properties of the food. Pectin degradation
during cooking resulted in increased mealiness. Nutritional components such as
carotenoids made the cassava yellow but also altered sweetness and softness;
however, yellow cassava was more appreciated by consumers than traditional
(white) varieties. Components formed during processing such as organic acids gave
fermented cassava products an acidic taste that was appreciated but the fermented
smell was not always liked. Anti-nutritional compounds such as cyanogenic
glucosides were mostly related to bitter taste. Post-harvest Physiological
Deterioration (PPD) affected the overall sensory characteristics and
acceptability. Genes responsible for some of these traits were also investigated.
Diversity in cassava food products can provide a challenge to identifying
acceptance criteria. Socio-economic factors such as gender may also be critical.
This review leads to questions in relation to the adaptation of cassava breeding
to meet consumer needs and preference in order to maximize income, health and
food security.
PMID- 27494197
TI - Comprehensive Characterization of Minichromosome Maintenance Complex (MCM)
Protein Interactions Using Affinity and Proximity Purifications Coupled to Mass
Spectrometry.
AB - The extensive identification of protein-protein interactions under different
conditions is an important challenge to understand the cellular functions of
proteins. Here we use and compare different approaches including affinity
purification and purification by proximity coupled to mass spectrometry to
identify protein complexes. We explore the complete interactome of the
minichromosome maintenance (MCM) complex by using both approaches for all of the
different MCM proteins. Overall, our analysis identified unique and shared
interaction partners and proteins enriched for distinct biological processes
including DNA replication, DNA repair, and cell cycle regulation. Furthermore, we
mapped the changes in protein interactions of the MCM complex in response to DNA
damage, identifying a new role for this complex in DNA repair. In summary, we
demonstrate the complementarity of these approaches for the characterization of
protein interactions within the MCM complex.
PMID- 27494203
TI - Authors' correction for Euro Surveill. 2016;21(29).
PMID- 27494204
TI - Mental health status following severe sulfur mustard exposure: a long-term study
of Iranian war survivors.
AB - INTRODUCTION: This study aimed to describe the mental health status of sulfur
mustard-exposed survivors suffering from severe respiratory and ophthalmological
problems. METHODS: Out of 450 invited Iran-Iraq War survivors of sulfur mustard
exposure with severe symptoms, 350 participated in this cross-sectional study.
Mental health status was assessed using the Diagnostic and Statistical Manual of
Mental Disorders, fourth edition, criteria. Fisher exact test, Pearson chi-square
test, and chi-square test were used to assess any relationship, and the
independent-sample t test was employed to compare differences between the
veterans with ocular and pulmonary injuries. RESULTS: There were 60.9% (n = 213)
survivors who suffered from mental disorders. Among them, 39.7% (n = 139) were
previously untreated and required the initiation of psychiatric treatment. The
prevalence of anxiety and mood disorders among all survivors was 40.6% (n = 142)
and 32.0% (n = 112), respectively. The most common anxiety and mood disorders
were posttraumatic stress disorder (32.9%, n = 115) and major depressive disorder
(22.3%, n = 78), respectively. Psychiatric disorders were more prevalent in cases
with severe pulmonary chemical injury than in subjects with severe ophthalmologic
chemical injury. Significant relationships were found between the types of
psychiatric disorders and age, education, and occupation (P < .05). CONCLUSION:
The psychiatric morbidity in the chemically injured populations was remarkable
and significantly different between the populations. The prevalence of mental
illness in these groups highlights the need for the appropriate provision of
mental health services.
PMID- 27494205
TI - Amorphous Semiconductor Nanowires Created by Site-Specific Heteroatom
Substitution with Significantly Enhanced Photoelectrochemical Performance.
AB - Semiconductor nanowires that have been extensively studied are typically in a
crystalline phase. Much less studied are amorphous semiconductor nanowires due to
the difficulty for their synthesis, despite a set of characteristics desirable
for photoelectric devices, such as higher surface area, higher surface activity,
and higher light harvesting. In this work of combined experiment and computation,
taking Zn2GeO4 (ZGO) as an example, we propose a site-specific heteroatom
substitution strategy through a solution-phase ions-alternative-deposition route
to prepare amorphous/crystalline Si-incorporated ZGO nanowires with tunable band
structures. The substitution of Si atoms for the Zn or Ge atoms distorts the
bonding network to a different extent, leading to the formation of amorphous
Zn1.7Si0.3GeO4 (ZSGO) or crystalline Zn2(GeO4)0.88(SiO4)0.12 (ZGSO) nanowires,
respectively, with different bandgaps. The amorphous ZSGO nanowire arrays exhibit
significantly enhanced performance in photoelectrochemical water splitting, such
as higher and more stable photocurrent, and faster photoresponse and recovery,
relative to crystalline ZGSO and ZGO nanowires in this work, as well as ZGO
photocatalysts reported previously. The remarkable performance highlights the
advantages of the ZSGO amorphous nanowires for photoelectric devices, such as
higher light harvesting capability, faster charge separation, lower charge
recombination, and higher surface catalytic activity.
PMID- 27494206
TI - Exploiting the Reactivity of Isocyanide: Coupling Reaction between Isocyanide and
Toluene Derivatives Using the Isocyano Group as an N1 Synthon.
AB - An unusual oxidative coupling reaction of isocyanide and toluene derivatives
using tetrabutylammonium iodide (TBAI) as a catalyst is disclosed. The
experimental results and mechanistic study show that the isocyano group acts
formally as an N1 synthon during the transformation, thus expanding the
reactivity profile of isocyanide.
PMID- 27494208
TI - Synthesis and Biological Evaluation of Several Bryostatin Analogues Bearing a
Diacylglycerol Lactone C-Ring.
AB - As an initial step in designing a simplified bryostatin hybrid molecule, three
bryostatin analogues bearing a diacylglycerol lactone-based C-ring, which
possessed the requisite pharmacophores for binding to protein kinase C (PKC)
together with a modified bryostatin-like A- and B-ring region, were synthesized
and evaluated. Merle 46 and Merle 47 exhibited binding affinity to PKC alpha with
Ki values of 7000 +/- 990 and 4940 +/- 470 nM, respectively. Reinstallation of
the trans-olefin and gem-dimethyl group present in bryostatin 1 in Merle 48
resulted in improved binding affinity, 363 +/- 42 nM. While Merle 46 and 47 were
only marginally active biologically, Merle 48 showed sufficient activity on the
U937 cells to confirm that it was PMA-like for growth and attachment, as
predicted by the substitution pattern of its A- and B-rings.
PMID- 27494207
TI - A novel EPID design for enhanced contrast and detective quantum efficiency.
AB - Beams-eye-view imaging applications such as real-time soft-tissue motion
estimation are hindered by the inherently low image contrast of electronic portal
imaging devices (EPID) currently available for clinical use. We introduce and
characterize a novel EPID design that provides substantially increased detective
quantum efficiency (DQE), contrast-to-noise ratio (CNR) and sensitivity without
degradation in spatial resolution. The prototype design features a stack of four
conventional EPID layers combined with low noise integrated readout electronics.
Each layer consists of a copper plate, a scintillator ([Formula: see text]) and a
photodiode/TFT-switch (aSi:H). We characterize the prototype's signal response to
a 6 MV photon beam in terms of modulation transfer function (MTF), DQE and CNR.
The presampled MTF is estimated using a slanted slit technique, the DQE is
calculated from measured normalized noise power spectra (nNPS) and the MTF and
CNR is estimated using a Las Vegas contrast phantom. The prototype has been
designed and built to be interchangeable with the current clinical EPID on the
Varian TrueBeam platform (AS-1200) in terms of size and data output
specifications. Performance evaluation is conducted in absolute values as well as
in relative terms using the Varian AS-1200 EPID as a reference detector. A
fivefold increase of DQE(0) to about 6.7% was observed by using the four-layered
design versus the AS-1200 reference detector. No substantial differences are
observed between each layer's individual MTF and the one for all four layers
operating combined indicating that defocusing due to beam divergence is
negligible. Also, using four layers instead of one increases the signal to noise
ratio by a factor of 1.7.
PMID- 27494209
TI - Nonclassical Phosphomolybdates with Different Degrees of Reduction: Syntheses and
Structural and Photo/Electrocatalytic Properties.
AB - Four nonclassical phosphomolybdates, formulated as
(H2pytty)8[{Mn(H2pytty)(H2O)3}{Sr?P6Mo6(V) Mo12(VI)O73}]2.16H2O (1),
[{Mn(H3pytty)(H2O)3}2{Sr?P6Mo4(V)Mo14(VI)O73}].18H2O (2), (H3pytp)
(H2pytty)2[{Fe(H2O)4}{Sr?P6Mo3(V)Mo15(VI)O73}].5H2O (3), and
(H2pytty)2[{Cd(H2O)4}{Cd(H2O)3 (H3pytty)}{Sr?P6Mo5(V)Mo13(VI)O73}].9H2O (4)
(pytty = 3-(pyrazin-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl; pytp = 4'
(4"-pyridyl)-2,4':6',4"-terpyridine) were hydrothermally synthesized and fully
characterized. The penta- and hexa-reduced basket clusters represent the highest
reduced level of basket-based polyoxometalate so far. In addition, transition
metal complexes as bridge units were introduced to basket system for the first
time to induce rare two-dimensional inorganic-organic hybrid layer. The results
indicate that reduced degrees of the basket clusters of compounds 1-4 can be
tuned by altering the molar ratio of organic ligand pytty and Na2MoO4. Compounds
1-4 exhibit bifunctional electrocatalytic behaviors for oxidation of dopamine and
reduction of H2O2. Electrocatalytic mechanism, chronoamperometric experiments and
electrocatalytic stability are studied in detail. In addition, the compounds show
highly efficient catalytic ability for the degradation of typical dyes under UV
irradiation.
PMID- 27494210
TI - Development and targeting of transcriptional regulatory network controlling FLU1
activation in Candida albicans for novel antifungals.
AB - Candidiasis caused by primarily Candida albicans poses serious threat due to dry
pipeline and ineffective antifungal strategy against resistance. In this study we
propose to target genes involved in efflux mediated Multi drug resistance. The
main objective of this study was to understand the regulatory interactions
responsible for activating a major MFS transporter gene of Candida albicans.
Another aim was to identify the docking effect of certain antifungal compounds
upon the transcription factor effectively controlling FLU1. The in silico study
carried out here aims at control of gene expression at initial levels. This
approach helps to understand regulatory control of FLU1 based on which a
predictive map was generated. This data focused on factors with major control
that could be suitable target for antifungal agents. The docking results confirm
the agreeable effect on the target transcription factor. Broadly this sort of
study would account for understanding and targeting any significant gene which in
turn would help in adjusting therapeutics accordingly. Further in silico ADMET
analysis reported positive values that are indicative of a good antifungal
compound with respect to pharmacokinetics. These tests are essential in
assessment of good drug candidates because they not only help in refining better
drug candidates but weeding out the unsuitable ones too.
PMID- 27494211
TI - Mechanical Stability of Flexible Graphene-Based Displays.
AB - The mechanical behavior of a prototype touch panel display, which consists of two
layers of CVD graphene embedded into PET films, is investigated in tension and
under contact-stress dynamic loading. In both cases, laser Raman spectroscopy was
employed to assess the stress transfer efficiency of the embedded graphene
layers. The tensile behavior was found to be governed by the "island-like"
microstructure of the CVD graphene, and the stress transfer efficiency was
dependent on the size of graphene "islands" but also on the yielding behavior of
PET at relatively high strains. Finally, the fatigue tests, which simulate real
operation conditions, showed that the maximum temperature gradient developed at
the point of "finger" contact after 80 000 cycles does not exceed the glass
transition temperature of the PET matrix. The effect of these results on future
product development and the design of new graphene-based displays are discussed.
PMID- 27494212
TI - Surface Adsorbed Antibody Characterization Using ToF-SIMS with Principal
Component Analysis and Artificial Neural Networks.
AB - Artificial neural networks (ANNs) form a class of powerful multivariate analysis
techniques, yet their routine use in the surface analysis community is limited.
Principal component analysis (PCA) is more commonly employed to reduce the
dimensionality of large data sets and highlight key characteristics. Herein, we
discuss the strengths and weaknesses of PCA and ANNs as methods for investigation
and interpretation of a complex multivariate sample set. Using time-of-flight
secondary ion mass spectrometry (ToF-SIMS) we acquired spectra from an antibody
and its proteolysis fragments with three primary-ion sources to obtain a panel of
72 spectra and a characteristic peak list of 775 fragment ions. We describe the
use of ANNs as a means to interpret the ToF-SIMS spectral data, highlight the
optimal neural network design and computational parameters, and discuss the
technique limitations. Further, employing Bi3(+) as the primary-ion source, ANNs
can accurately classify antibody fragments from the parent antibody based on ToF
SIMS spectra.
PMID- 27494213
TI - Lack of relationship between masticatory performance and nutritional status in
adults with natural dentition.
AB - OBJECTIVE: This study assessed the relation among several aspects of the
masticatory function and the nutritional status in adults with natural dentition.
DESIGN: One hundred adults with natural dentition participated in this cross
sectional study. They performed one free-style masticatory test consisting of
five trials of 20 silicon-chewing cycles. The preferred chewing side was
determined by calculating the asymmetry index. Masticatory performance was
determined by sieving the silicon particles, and the cycle duration was also
recorded. Weight, body water percentage, body fat mass, muscle mass and osseous
mass were measured using a portable digital weighing machine. Body mass index
(BMI), waist-hip ratio, skinfold thickness and the upper-arm composition were
determined. The relation between masticatory function and a nutritional variable
were tested using Pearson or Spearman rank correlation coefficients or using
analysis of variance or the Kruskal-Wallis H-test and the Mann-Whitney U test, as
appropriate. RESULTS: Whereas body fat percentages for women were significantly
higher than for men, the body mass index was higher in men than in women.
Participants who were underweight chewed more asymmetrically and more slowly than
normal weight or obese participants. A negative correlation was observed between
body fat percentage and masticatory laterality. No relation between masticatory
performance and any nutritional status indicator was detected. CONCLUSION: Being
underweight and having a low body fat percentage seem to be related to a
masticatory lateral asymmetry and to a large cycle duration in young adults with
natural dentition. Masticatory performance does not seem to be related to
nutritional status.
PMID- 27494218
TI - CORRIGENDUM: Comprehensive analysis via exome sequencing uncovers genetic
etiology in autosomal recessive nonsyndromic deafness in a large multiethnic
cohort.
PMID- 27494214
TI - Revisiting the photosystem II repair cycle.
AB - The ability of photosystem (PS) II to catalyze the light-driven oxidation of
water comes along with its vulnerability to oxidative damage, in particular of
the D1 core subunit. Photodamaged PSII undergoes repair in a multi-step process
involving (i) reversible phosphorylation of PSII core subunits; (ii)
monomerization and lateral migration of the PSII core from grana to stroma
thylakoids; (iii) partial disassembly of PSII; (iv) proteolytic degradation of
damaged D1; (v) replacement of damaged D1 protein with a new copy; (vi)
reassembly of PSII monomers and migration back to grana thylakoids for
dimerization and supercomplex assembly. Here we review the current knowledge on
the PSII repair cycle.
PMID- 27494215
TI - Biological Testing of Organophosphorus-Inactivated Acetylcholinesterase Oxime
Reactivators Identified via Virtual Screening.
AB - There is a pressing need for new therapeutics to reactivate covalently
inactivated acetylcholinesterase (AChE) due to exposure to organophosphorus (OP)
compounds. Current reactivation therapeutics (RTs) are not broad-spectrum and
suffer from other liabilities, specifically the inability to cross the blood
brain-barrier. Additionally, the chemical diversity of available therapeutics is
small, limiting opportunities for structure-activity relationship (SAR) studies
to aid in the design of more effective compounds. In order to find new starting
points for the development of oxime-containing therapeutic reactivators and to
increase our base of knowledge, we have employed a combination of computational
and experimental procedures to identify additional compounds with the real or
potential ability to reactivate AChE while augmenting and complementing current
knowledge. Computational methods were used to identify previously uninvestigated
oxime-containing molecules. Experimentally, six compounds were found with
reactivation capabilities comparable to, or exceeding, those of 2-pralidoxime (2
PAM) against a panel of AChE inactivated by paraoxon, diisopropylfluorophosphate
(DFP), fenamiphos, and methamidophos. One compound showed enhanced reactivation
ability against DFP and fenamiphos, the least tractable of these OPs to be
reactivated.
PMID- 27494219
TI - Biophysical influence of coumarin 35 on bovine serum albumin: Spectroscopic
study.
AB - The binding mechanism and protein-fluorescence probe interactions between bovine
serum albumin (BSA) and coumarin 35 (C35) was investigated by using UV-Vis
absorption and fluorescence spectroscopies since they remain major research
topics in biophysics. The spectroscopic data indicated that a fluorescence
quenching process for BSA-C35 system was occurred. The fluorescence quenching
processes were analyzed using Stern-Volmer method. In this regard, Stern-Volmer
quenching constants (KSV) and binding constants were calculated at different
temperatures. The distance r between BSA (donor) and C35 (acceptor) was
determined by exploiting fluorescence resonance energy transfer (FRET) method.
Synchronous fluorescence spectra were also studied to observe information about
conformational changes. Moreover, thermodynamics parameters were calculated for
better understanding of interactions and conformational changes of the system.
PMID- 27494222
TI - What Makes Us Whole?
PMID- 27494220
TI - Quinazolinone derivative: Model compound for determination of dipole moment,
solvatochromism and metal ion sensing.
AB - A dihydroquinazolinone derivative 2-(2,4-Dimethoxy-phenyl)-2,3-dihydro-1H
quinazolin-4-one (1) was synthesized and characterized by 1H NMR, 13C NMR and FT
IR and its spectral, photophysical, intramolecular charge transfer
characteristics were studied by absorption and emission spectroscopy. The
compound exhibits significant changes in their photophysical properties depending
on the solvent polarity. The observed bathochromic emission band and difference
in Stokes shift on changing the polarity of the solvents clearly demonstrate the
highly polar character of the excited state, which is also supported by the
enhancement of dipole moment of the molecule upon photoexcitation. Solvatochromic
shift methods based on Lippert-Mataga, Bakhshiev-Kawski and Reichardt's
correlations were applied to calculate the ground, excited and change in dipole
moments. The effect of solute-solvent interactions on compound 1 was studied
using multi-parameter solvent polarity scales proposed by Kamlet-Taft and
Catalan. The interactions of various metal ions on compound 1 were also studied
using steady state fluorescence measurements. The emission profile reveals that
it acts as on-off type fluorescent chemosensor for selective and sensitive
detection of Hg2+ions. Complexation stoichiometry and mechanism of quenching were
determined from Benesi-Hildebrand and Stern-Volmer plot.
PMID- 27494223
TI - Prevalence and Implications of Abnormal Laboratory Results in Patients in the
Terminal Phase of Life.
AB - BACKGROUND: Pathophysiological changes at the end of life may affect
pharmacokinetics of drugs. However, caregivers typically do not extensively
monitor patients' laboratory parameters at the end of life. OBJECTIVE: Our aim
was to describe laboratory parameters of hospice patients in the week before
death. METHODS: A cohort study was conducted on available laboratory results in
the week before death, including clinical chemistry and hematology tests.
RESULTS: Laboratory data of 125 patients in a palliative care center were
included, assessed at a median of 3 days before death. Eighty percent of patients
had anemia and almost all had hypoalbuminemia (97%). Elevated levels of gamma
glutamyl transferase (gGT) were found in 75%, of alkaline phosphatase (ALP) in
60%, of aspartate aminotransferase (ASAT) in 60%, and of calcium (Ca) in 68%.
Alanine aminotransferase (ALAT), bilirubin, sodium (Na), and potassium (K) were
abnormal in from 8.8% to 36.0% of patients. A previous unknown poor kidney
function was found in 60% of patients. Thirteen patients (22%) with a regular
morphine prescription and one patient treated with a non-steroidal anti
inflammatory drug (NSAID) had severe kidney failure. CONCLUSIONS: Abnormal
laboratory results were expected due to the pathophysiological changes that occur
during the last phase of life. Remarkably, however, electrolytes (Na and K) were
balanced even shortly before death. Estimated glomerular filtration rate (eGFR),
reflecting the kidney function, seems the most clinically relevant laboratory
parameter, because it may guide drug choice and dosing.
PMID- 27494224
TI - Opioids for Chronic Pain in Patients with History of Substance Use Disorders,
Part 1: Assessment and Initiation #311.
PMID- 27494225
TI - Opioids for Chronic Pain in Patients with History of Substance Use Disorders,
Part 2: Management and Monitoring #312.
PMID- 27494226
TI - Meaningful Use.
PMID- 27494227
TI - Sampling Molecular Conformers in Solution with Quantum Mechanical Accuracy at a
Nearly Molecular-Mechanics Cost.
AB - We introduce a method to evaluate the relative populations of different
conformers of molecular species in solution, aiming at quantum mechanical
accuracy, while keeping the computational cost at a nearly molecular-mechanics
level. This goal is achieved by combining long classical molecular-dynamics
simulations to sample the free-energy landscape of the system, advanced
clustering techniques to identify the most relevant conformers, and thermodynamic
perturbation theory to correct the resulting populations, using quantum
mechanical energies from density functional theory. A quantitative criterion for
assessing the accuracy thus achieved is proposed. The resulting methodology is
demonstrated in the specific case of cyanin (cyanidin-3-glucoside) in water
solution.
PMID- 27494228
TI - Binding of estrogen receptors to switch sites and regulatory elements in the
immunoglobulin heavy chain locus of activated B cells suggests a direct influence
of estrogen on antibody expression.
AB - Females and males differ in antibody isotype expression patterns and in immune
responses to foreign- and self-antigens. For example, systemic lupus
erythematosus is a condition that associates with the production of isotype
skewed anti-self antibodies, and exhibits a 9:1 female:male disease ratio. To
explain differences between B cell responses in males and females, we sought to
identify direct interactions of the estrogen receptor (ER) with the
immunoglobulin heavy chain locus. This effort was encouraged by our previous
identification of estrogen response elements (ERE) in heavy chain switch (S)
regions. We conducted a full-genome chromatin immunoprecipitation analysis (ChIP
seq) using DNA from LPS-activated B cells and an ERalpha-specific antibody.
Results revealed ER binding to a wide region of DNA, spanning sequences from the
JH cluster to Cdelta, with peaks in EMU and SMU sites. Additional peaks of
ERalpha binding were coincident with hs1,2 and hs4 sites in the 3' regulatory
region (3'RR) of the heavy chain locus. This first demonstration of direct
binding of ER to key regulatory elements in the immunoglobulin locus supports our
hypothesis that estrogen and other nuclear hormone receptors and ligands may
directly influence antibody expression and class switch recombination (CSR). Our
hypothesis encourages the conduct of new experiments to evaluate the consequences
of ER binding. A better understanding of ER:DNA interactions in the
immunoglobulin heavy chain locus, and respective mechanisms, may ultimately
translate to better control of antibody expression, better protection against
pathogens, and prevention of pathologies caused by auto-immune disease.
PMID- 27494229
TI - 2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis
patients and promotes clearance of amyloid deposits by phagocytosis ?.
AB - Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain
(LC) (amyloid) deposition in various peripheral organs, leading to progressive
dysfunction and death. There are no regulatory agency-approved treatments for AL
amyloidosis, and none of the available standard of care approaches directly
targets the LC protein that constitutes the amyloid. NEOD001, currently in late
stage clinical trials, is a conformation-specific, anti-LC antibody designed to
specifically target misfolded LC aggregates and promote phagocytic clearance of
AL amyloid deposits. The present study demonstrated that the monoclonal antibody
2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble
LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4
specifically labeled all 21 fresh-frozen organ samples studied, which were
derived from 10 patients representing both kappa and lambda LC amyloidosis
subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T-positive
labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from
patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic
clearance of AL amyloid deposits in vitro. These findings provide further
evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from
tissue and further support the rationale for the evaluation of NEOD001 in
patients with AL amyloidosis.
PMID- 27494231
TI - Non-steroidal anti-inflammatories and the development of analgesic nephropathy: a
systematic review.
AB - BACKGROUND: Analgesic nephropathy (AN) is chronic renal impairment as a direct
consequence of chronic heavy analgesia ingestion. An association between non
steroidal anti-inflammatory agents and chronic kidney disease (CKD) has long been
suspected. Despite ample observational data obtained in recent decades the
relationship remains uncertain. This systematic review intends to summarize the
available literature and to define the role of non-steroidal anti-inflammatories
in the natural history of AN. METHODS: We conducted a systematic literature
search for articles describing the association between non-steroidal anti
inflammatory abuse and renal insufficiency. No restriction was placed on
publication date, but papers were limited to English language, observational
design, and human studies. RESULTS: Nine articles met our inclusion criteria and
were discussed in this review. This includes 5 cohort studies and 4 case-control
trials, with a combined population of 12,418 study subjects and 23,877 controls.
Eight of the nine reports failed to identify any increased risk of chronic renal
impairment with heavy non-steroidal anti-inflammatory consumption. Study methods
were heterogeneous and the overall quality of data was relatively poor.
CONCLUSION: A relationship between non-steroidal anti-inflammatory medicines and
the development of CKD has never been proven. Based on the available scientific
evidence non-steroidal anti-inflammatory agents do not appear to be implicated in
the pathogenesis of AN.
PMID- 27494230
TI - Preparation of a reproducible long-acting formulation of risperidone-loaded PLGA
microspheres using microfluidic method.
AB - The aim of the present study is to prepare risperidone-loaded poly lactic-co
glycolic acid (PLGA) microspheres within microfluidic system and to achieve a
formulation with uniform size and monotonic and reproducible release profile. In
comparison to batch method, T-junction and serpentine chips were utilized and
optimizing study was carried out at different processing parameters (e.g. PLGA
and surfactant concentration and flow rates ratio of outer to inner phase). The
computational fluid dynamic (CFD) modeling was performed, and loading and release
study were carried out. CFD simulation indicates that increasing the flow rate of
aqueous phase cause to decrease the droplet size, while the change in size of
microspheres did not follow a specific pattern in the experimental results. The
most uniform microspheres and narrowest standard deviation (66.79 MUm +/- 3.32)
were achieved using T-junction chip, 1% polyvinylalcohol, 1% PLGA and flow rates
ratio of 20. The microfluidic-assisted microspheres were more uniform with
narrower size distribution. The release of risperidone from microspheres produced
by the microfluidic method was more reproducible and closer to zero-order kinetic
model. The release profile of formulation with 2:1 drug-to-polymer ratio was the
most favorable release, in which 41.85% release could be achieved during 24 days.
PMID- 27494232
TI - Can breast microbiota provide protective effects against cancer?
PMID- 27494233
TI - The study of polymorphic states of paradichlorobenzene by means of nuclear
quadrupole resonance relaxometry.
AB - The article describes the results of the experimental study of the molecular
crystal of paradichlorobenzene in alpha- and beta-phases by means of NQR
relaxometry with the inversion of Laplace transformation. The anisotropy effect
of the pore space of wood on the distribution of times of the spin-lattice
relaxation of p-C6H4Cl2 in the pores of pre-impregnated with the molten sample is
shown. It was established that the increase in the T1 spin-lattice relaxation
time of (35)Cl nucleus in the wood pores (channels) is observed in the case when
the radio frequency field B1 is parallel to the tracheid's of wood. The NQR T1rho
dispersion analysis of paradichlorobenzene in alpha-phase was carried out for the
first time.
PMID- 27494235
TI - Combretastatin A-4 Analogue: A Dual-Targeting and Tubulin Inhibitor Containing
Antitumor Pt(IV) Moiety with a Unique Mode of Action.
AB - Three new Pt(IV) complexes comprising a combretastatin A-4 analogue were designed
and synthesized. The resulting antitumor Pt(IV) complexes could significantly
improve the antiproliferative activity and overcome the drug resistance of
cisplatin in vitro. Interestingly, these novel compounds not only can carry the
DNA binding Pt(II) warhead into the cancer cells but also have a small molecule
fragment that can inhibit tubulin polymerization. Among them, complex 13, which
was attached to an inhibitor of tubulin at one axial position of Pt(IV)
octahedral coordination sphere, could effectively enter cancer cells, arrest the
cell cycle in HepG-2 cancer cells at G2/M phases, and induce activation of
caspases triggering apoptotic signaling via the mitochondrial-dependent apoptosis
pathways. Moreover, complex 13 has the ability to effectively inhibit the tumor
growth in the HepG-2 xenograft model without causing significant loss of animal
body weight in comparison with cisplatin.
PMID- 27494234
TI - Inhibition of Prolyl Hydroxylase Attenuates Fas Ligand-Induced Apoptosis and Lung
Injury in Mice.
AB - Alveolar epithelial injury and increased alveolar permeability are hallmarks of
acute respiratory distress syndrome. Apoptosis of lung epithelial cells via the
Fas/Fas ligand (FasL) pathway plays a critical role in alveolar epithelial
injury. Activation of hypoxia-inducible factor (HIF)-1 by inhibition of prolyl
hydroxylase domain proteins (PHDs) is a possible therapeutic approach to
attenuate apoptosis and organ injury. Here, we investigated whether treatment
with dimethyloxalylglycine (DMOG), an inhibitor of PHDs, could attenuate Fas/FasL
dependent apoptosis in lung epithelial cells and lung injury. DMOG increased HIF
1alpha protein expression in vitro in MLE-12 cells, a murine alveolar epithelial
cell line. Treatment of MLE-12 cells with DMOG significantly suppressed cell
surface expression of Fas and attenuated FasL-induced caspase-3 activation and
apoptotic cell death. Inhibition of the HIF-1 pathway by echinomycin or small
interfering RNA transfection abolished these antiapoptotic effects of DMOG.
Moreover, intraperitoneal injection of DMOG in mice increased HIF-1alpha
expression and decreased Fas expression in lung tissues. DMOG treatment
significantly attenuated caspase-3 activation, apoptotic cell death in lung
tissue, and the increase in alveolar permeability in mice instilled
intratracheally with FasL. In addition, inflammatory responses and
histopathological changes were also significantly attenuated by DMOG treatment.
In conclusion, inhibition of PHDs protects lung epithelial cells from Fas/FasL
dependent apoptosis through HIF-1 activation and attenuates lung injury in mice.
PMID- 27494236
TI - Nonhuman Animals, Public Health, and Ethics: A First Step, But....
AB - In December 2015, the Johns Hopkins Bloomberg School of Public Health held the
first-ever summit on the intersection between nonhuman animal ethics and human
health. The conference covered a variety of issues where animal health intersects
with human health, including the wildlife trade, animal agriculture, and animal
experimentation. This article provides a brief overview and critique of the
summit.
PMID- 27494237
TI - Two interesting cases of intracranial IgG4-related disease and discussion of
therapy options.
PMID- 27494239
TI - Spread of health behaviors in young couples: How relationship power shapes
relational influence.
AB - INTRODUCTION: Romantic relationships provide a context in which partners can
influence each other's health behaviors (e.g., weight-related behaviors,
substance use). Partner influence may be especially pronounced among newly
parenting adolescent and young adult couples because of the desire to maintain
relationships (and therefore openness to influence), and because parenting
related challenges can pose risk for uptake of unhealthy behaviors. Two
understudied factors that might affect partner influence on health behaviors
include relative power within the relationship and prior levels of engagement in
health behaviors. METHODS: The current study explored longitudinal partner
influence effects in a sample of newly parenting adolescent and young adult
females and their male partners (Ncouples = 157) recruited from four
obstetrics/gynecology clinics in Connecticut between July 2007 and February 2011.
Five health behaviors in two domains were explored: weight-related behaviors
(unhealthy eating, exercise) and substance use (cigarette, alcohol, and marijuana
use). Relationship power and previous levels of health behaviors were examined as
moderators. Variations across gender were also examined. RESULTS: Results of
dyadic analysis showed partner influences for alcohol use. Partner influence
depended on relationship power for eating, alcohol, and marijuana use, and on
previous behavior for cigarette use. Results also varied by gender - only female
to-male influence was found for unhealthy eating and cigarette use. Higher
relationship power was protective against smoking escalation for females.
DISCUSSION: These results differ from previous research findings mainly on male
to-female influences. Such asymmetries may reflect traditional female dominance
in food preparation, as well as shifts in power balances postpartum. Targeting
relational power dynamics may buffer the spread and escalation of unhealthy
behaviors in young parents, with implications for the health of both members of a
couple as well as their children.
PMID- 27494241
TI - The Relationship between Metabolically Obese Non-Obese Weight and Stroke: The
Korea National Health and Nutrition Examination Survey.
AB - OBJECTIVE: Both metabolic syndrome (MetS) and obesity increase the risk of
stroke. However, few studies have compared the risks of stroke associated with
metabolically obese non-obese weight (MONW) and metabolically healthy obesity
(MHO). This study aimed to compare the prevalence of stroke in MONW and MHO
individuals. METHODS: A total of 25,744 subjects aged >=40 years were selected
from the 2007-2014 Korean National Health and Nutrition Examination Survey. MetS
was defined using 2001 National Cholesterol Education Program/Adult Treatment
Panel III and 2005 American Heart Association/National Heart, Lung, and Blood
Institute criteria. Non-obese weight and obesity were defined as a body mass
index (BMI) <25 kg/m2 and >=25 kg/m2, respectively. MONW was defined as meeting
the MetS criteria with a BMI <25 kg/m2 and MHO was defined as not meeting the
MetS criteria with a BMI >=25 kg/m2. RESULTS: Women with MONW had a higher
prevalence of stroke than those with MHO (odds ratio [OR] = 2.27, 95% confidence
interval [CI]: 1.45-3.57). The prevalence of stroke increased as the number of
MetS components increased. The ORs for MONW with 3, 4, and 5 MetS components were
1.95 (95% CI: 1.19-3.21), 2.49 (95% CI: 1.46-4.24) and 2.74 (95% CI: 1.39-5.40),
respectively. CONCLUSIONS: Our study findings may better emphasize the risk of
stroke among more lean but unhealthy individuals, who appear healthy but may be
suffering from MetS. These findings also highlight the need for stroke risk
factor assessment in non-obese weight individuals.
PMID- 27494240
TI - The emotional cost of distance: Geographic social network dispersion and post
traumatic stress among survivors of Hurricane Katrina.
AB - RATIONALE: Social networks offer important emotional and instrumental support
following natural disasters. However, displacement may geographically disperse
network members, making it difficult to provide and receive support necessary for
psychological recovery after trauma. OBJECTIVES: We examine the association
between distance to network members and post-traumatic stress using survey data,
and identify potential mechanisms underlying this association using in-depth
qualitative interviews. METHODS: We use longitudinal, mixed-methods data from the
Resilience in Survivors of Katrina (RISK) Project to capture the long-term
effects of Hurricane Katrina on low-income mothers from New Orleans. Baseline
surveys occurred approximately one year before the storm and follow-up surveys
and in-depth interviews were conducted five years later. We use a sequential
explanatory analytic design. With logistic regression, we estimate the
association of geographic network dispersion with the likelihood of post
traumatic stress. With linear regressions, we estimate the association of network
dispersion with the three post-traumatic stress sub-scales. Using maximal
variation sampling, we use qualitative interview data to elaborate identified
statistical associations. RESULTS: We find network dispersion is positively
associated with the likelihood of post-traumatic stress, controlling for
individual-level socio-demographic characteristics, exposure to hurricane-related
trauma, perceived social support, and New Orleans residency. We identify two
social-psychological mechanisms present in qualitative data: respondents with
distant network members report a lack of deep belonging and a lack of mattering
as they are unable to fulfill obligations to important distant ties. CONCLUSION:
Results indicate the importance of physical proximity to emotionally-intimate
network ties for long-term psychological recovery.
PMID- 27494243
TI - Exonuclease 1 and its versatile roles in DNA repair.
AB - Exonuclease 1 (EXO1) is a multifunctional 5' -> 3' exonuclease and a DNA
structure-specific DNA endonuclease. EXO1 plays roles in DNA replication, DNA
mismatch repair (MMR) and DNA double-stranded break repair (DSBR) in lower and
higher eukaryotes and contributes to meiosis, immunoglobulin maturation, and
micro-mediated end-joining in higher eukaryotes. In human cells, EXO1 is also
thought to play a role in telomere maintenance. Mutations in the human EXO1 gene
correlate with increased susceptibility to some cancers. This review summarizes
recent studies on the enzymatic functions and biological roles of EXO1, its
possible protective role against cancer and aging, and regulation of EXO1 by
posttranslational modification.
PMID- 27494244
TI - Flow Cytometry in Detection of Fetal Red Blood Cells and Maternal F Cells to
Identify Fetomaternal Hemorrhage.
AB - Accurate detection and quantitation of fetomaternal hemorrhage (FMH) is critical
to the obstetric management of rhesus D alloimmunization in Rh-negative pregnant
women. The flow cytometry is based on the detection of fetal red blood cells
using a monoclonal anti-HbF antibody, and is the method most indicated for this
estimation. The objective of this study was to quantify fetal red blood cell
levels of pregnant women using flow cytometry. We analyzed 101 peripheral blood
samples from Rh-negative and Rh-positive women, whose mean age was 24 years (20
32 years), after vaginal delivery or cesarean section. Our study showed that 53%
of pregnant women had fetal red blood cells levels <2.0 mL, 31% between 2.0-3.9
mL, 16% between 4.0-15.0 mL, and 1% >15.0 mL. Accurate quantitation of fetal red
blood cells is necessary to determine the appropriate dose of anti-D (RHD)
immunoglobulin to be administered to pregnant or postpartum women.
PMID- 27494247
TI - Climatic conditions and child height: Sex-specific vulnerability and the
protective effects of sanitation and food markets in Nepal.
AB - Environmental conditions in early life are known to have impacts on later health
outcomes, but causal mechanisms and potential remedies have been difficult to
discern. This paper uses the Nepal Demographic and Health Surveys of 2006 and
2011, combined with earlier NASA satellite observations of variation in the
Normalized Difference Vegetation Index (NDVI) at each child's location and time
of birth to identify the trimesters of gestation and periods of infancy when
climate variation is linked to attained height later in life. We find significant
differences by sex: males are most affected by conditions in their second
trimester of gestation, and females in the first three months after birth. Each
100-point difference in NDVI at those times is associated with a difference in
height-for-age z-score (HAZ) measured at age 12-59 months of 0.088 for boys and
0.054 for girls, an effect size similar to that of moving within the distribution
of household wealth by close to one quintile for boys and one decile for girls.
The entire seasonal change in NDVI from peak to trough is approximately 200-300
points during the 2000-2011 study period, implying a seasonal effect on HAZ
similar to one to three quintiles of household wealth. This effect is observed
only in households without toilets; in households with toilets, there is no
seasonal fluctuation, implying protection against climatic conditions that
facilitate disease transmission. We also use data from the Nepal Living Standards
Surveys on district-level agricultural production and marketing, and find a
climate effect on child growth only in districts where households' food
consumption derives primarily from their own production. Robustness tests find no
evidence of selection effects, and placebo regression results reveal no
significant artefactual correlations. The timing and sex-specificity of climatic
effects are consistent with previous studies, while the protective effects of
household sanitation and food markets are novel indications of mechanisms by
which households can gain resilience against adverse climatic conditions.
PMID- 27494248
TI - Overloaded and stressed: whole-cell considerations for bacterial synthetic
biology.
AB - The predictability and robustness of engineered bacteria depend on the many
interactions between synthetic constructs and their host cells. Expression from
synthetic constructs is an unnatural load for the host that typically reduces
growth, triggers stresses and leads to decrease in performance or failure of
engineered cells. Work in systems and synthetic biology has now begun to address
this through new tools, methods and strategies that characterise and exploit host
construct interactions in bacteria. Focusing on work in E. coli, we review here a
selection of the recent developments in this area, highlighting the emerging
issues and describing the new solutions that are now making the synthetic biology
community consider the cell just as much as they consider the construct.
PMID- 27494246
TI - Use of In Vitro Assays to Assess Immunogenicity Risk of Antibody-Based
Biotherapeutics.
AB - An In Vitro Comparative Immunogenicity Assessment (IVCIA) assay was evaluated as
a tool for predicting the potential relative immunogenicity of biotherapeutic
attributes. Peripheral blood mononuclear cells from up to 50 healthy naive human
donors were monitored up to 8 days for T-cell proliferation, the number of IL-2
or IFN-gamma secreting cells, and the concentration of a panel of secreted
cytokines. The response in the assay to 10 monoclonal antibodies was found to be
in agreement with the clinical immunogenicity, suggesting that the assay might be
applied to immunogenicity risk assessment of antibody biotherapeutic attributes.
However, the response in the assay is a measure of T-cell functional activity and
the alignment with clinical immunogenicity depends on several other factors. The
assay was sensitive to sequence variants and could differentiate single point
mutations of the same biotherapeutic. Nine mAbs that were highly aggregated by
stirring induced a higher response in the assay than the original mAbs before
stirring stress, in a manner that did not match the relative T-cell response of
the original mAbs. In contrast, mAbs that were glycated by different sugars
(galactose, glucose, and mannose) showed little to no increase in response in the
assay above the response to the original mAbs before glycation treatment. The
assay was also used successfully to assess similarity between multiple lots of
the same mAb, both from the same manufacturer and from different manufacturers
(biosimilars). A strategy for using the IVCIA assay for immunogenicity risk
assessment during the entire lifespan development of biopharmaceuticals is
proposed.
PMID- 27494249
TI - Response: letter to the editor.
PMID- 27494250
TI - Underreporting and Missed Opportunities for Uptake of Intermittent Preventative
Treatment of Malaria in Pregnancy (IPTp) in Mali.
AB - OBJECTIVES: To identify factors contributing to low uptake of intermittent
preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp
SP) in rural Mali. METHODS: We conducted secondary data analysis on Mali's 2012
2013 Demographic and Health Survey (DHS) to determine the proportion of women who
failed to take IPTp-SP due to ineligibility or non-attendance at antenatal care
(ANC). We also identified the proportion who reported taking other or unknown
medications to prevent malaria in pregnancy and those who did not know if they
took any medication to prevent malaria in pregnancy. We conducted qualitative
interviews, focus groups and ANC observations in six rural sites in Mali's
Sikasso and Koulikoro regions to identify reasons for missed opportunities.
RESULTS: Our secondary data analysis found that reported IPTp-SP coverage
estimates are misleading due to their dependence on a variable ("source of IPTp")
that is missing 62% of its data points. Among all women who gave birth in the two
years prior to the survey, 56.2% reported taking at least one dose of IPTp-SP.
Another 5.2% reported taking chloroquine, 1.9% taking another drug to prevent
malaria in pregnancy, 4.4% not knowing what drug they took to prevent malaria,
and 1.1% not knowing if they took any drug to prevent malaria. The majority of
women who did not receive IPTp-SP were women who also did not attend ANC. Our
qualitative data revealed that many health centers neither administer IPTp-SP by
directly observed therapy, nor give IPTp-SP at one month intervals through the
second and third trimesters, nor provide IPTp-SP free of charge. Women generally
reported IPTp-SP as available and tolerable, but frequently could not identify
its name or purpose, potentially affecting accuracy of responses in household
surveys. CONCLUSION: We estimate IPTp-SP uptake to be significantly higher than
stated in Mali's 2012-13 DHS report. Increasing ANC attendance should be the
first priority for increasing IPTp-SP coverage. Reducing cost and access
barriers, ensuring that providers follow up-to-date guidelines, and improving
patient counseling on IPTp-SP would also facilitate optimal uptake.
PMID- 27494251
TI - Failure to Burrow and Tunnel Reveals Roles for jim lovell in the Growth and
Endoreplication of the Drosophila Larval Tracheae.
AB - The Drosophila protein Jim Lovell (Lov) is a putative transcription factor of the
BTB/POZ (Bric- a-Brac/Tramtrack/Broad/ Pox virus and Zinc finger) domain class
that is expressed in many elements of the developing larval nervous system. It
has roles in innate behaviors such as larval locomotion and adult courtship. In
performing tissue-specific knockdown with the Gal4-UAS system we identified a new
behavioral phenotype for lov: larvae failed to burrow into their food during
their growth phase and then failed to tunnel into an agarose substratum during
their wandering phase. We determined that these phenotypes originate in a
previously unrecognized role for lov in the tracheae. By using tracheal-specific
Gal4 lines, Lov immunolocalization and a lov enhancer trap line, we established
that lov is normally expressed in the tracheae from late in embryogenesis through
larval life. Using an assay that monitors food burrowing, substrate tunneling and
death we showed that lov tracheal knockdown results in tracheal fluid-filling,
producing hypoxia that activates the aberrant behaviors and inhibits development.
We investigated the role of lov in the tracheae that initiates this sequence of
events. We discovered that when lov levels are reduced, the tracheal cells are
smaller, more numerous and show lower levels of endopolyploidization. Together
our findings indicate that Lov is necessary for tracheal endoreplicative growth
and that its loss in this tissue causes loss of tracheal integrity resulting in
chronic hypoxia and abnormal burrowing and tunneling behavior.
PMID- 27494252
TI - Comparison of Detailed and Simplified Models of Human Atrial Myocytes to
Recapitulate Patient Specific Properties.
AB - Computer studies are often used to study mechanisms of cardiac arrhythmias,
including atrial fibrillation (AF). A crucial component in these studies is the
electrophysiological model that describes the membrane potential of myocytes. The
models vary from detailed, describing numerous ion channels, to simplified,
grouping ionic channels into a minimal set of variables. The parameters of these
models, however, are determined across different experiments in varied species.
Furthermore, a single set of parameters may not describe variations across
patients, and models have rarely been shown to recapitulate critical features of
AF in a given patient. In this study we develop physiologically accurate
computational human atrial models by fitting parameters of a detailed and of a
simplified model to clinical data for five patients undergoing ablation therapy.
Parameters were simultaneously fitted to action potential (AP) morphology, action
potential duration (APD) restitution and conduction velocity (CV) restitution
curves in these patients. For both models, our fitting procedure generated
parameter sets that accurately reproduced clinical data, but differed markedly
from published sets and between patients, emphasizing the need for patient
specific adjustment. Both models produced two-dimensional spiral wave dynamics
for that were similar for each patient. These results show that simplified,
computationally efficient models are an attractive choice for simulations of
human atrial electrophysiology in spatially extended domains. This study
motivates the development and validation of patient-specific model-based
mechanistic studies to target therapy.
PMID- 27494253
TI - Ecosystem Carbon Storage in Alpine Grassland on the Qinghai Plateau.
AB - The alpine grassland ecosystem can sequester a large quantity of carbon, yet its
significance remains controversial owing to large uncertainties in the relative
contributions of climate factors and grazing intensity. In this study we surveyed
115 sites to measure ecosystem carbon storage (both biomass and soil) in alpine
grassland over the Qinghai Plateau during the peak growing season in 2011 and
2012. Our results revealed three key findings. (1) Total biomass carbon density
ranged from 0.04 for alpine steppe to 2.80 kg C m-2 for alpine meadow. Median
soil organic carbon (SOC) density was estimated to be 16.43 kg C m-2 in alpine
grassland. Total ecosystem carbon density varied across sites and grassland
types, from 1.95 to 28.56 kg C m-2. (2) Based on the median estimate, the total
carbon storage of alpine grassland on the Qinghai Plateau was 5.14 Pg, of which
94% (4.85 Pg) was soil organic carbon. (3) Overall, we found that ecosystem
carbon density was affected by both climate and grazing, but to different
extents. Temperature and precipitation interaction significantly affected AGB
carbon density in winter pasture, BGB carbon density in alpine meadow, and SOC
density in alpine steppe. On the other hand, grazing intensity affected AGB
carbon density in summer pasture, SOC density in alpine meadow and ecosystem
carbon density in alpine grassland. Our results indicate that grazing intensity
was the primary contributing factor controlling carbon storage at the sites
tested and should be the primary consideration when accurately estimating the
carbon storage in alpine grassland.
PMID- 27494255
TI - Quantification of Hepatic Vascular and Parenchymal Regeneration in Mice.
AB - BACKGROUND: Liver regeneration consists of cellular proliferation leading to
parenchymal and vascular growth. This study complements previous studies on
cellular proliferation and weight recovery by (1) quantitatively describing
parenchymal and vascular regeneration, and (2) determining their relationship.
Both together are needed to (3) characterize the underlying growth pattern.
METHODS: Specimens were created by injecting a polymerizing contrast agent in
either portal or hepatic vein in normal or regenerating livers after 70% partial
hepatectomy. 3D image data were obtained through micro-CT scanning. Parenchymal
growth was assessed by determining weight and volume of the regenerating liver.
Vascular growth was described by manually determined circumscribed parameters
(maximal vessel length and radius of right inferior portal/hepatic vein),
automatically determined cumulative parameters (total edge length and total
vascular volume), and parameters describing vascular density (total edge
length/volume, vascular volume fraction). The growth pattern was explored by
comparing the relative increase of these parameters to the increase expected in
case of isotropic expansion. RESULTS: Liver volume recovery paralleled weight
recovery and reached 90% of the original liver volume within 7 days. Comparing
radius-related vascular parameters immediately after surgical resection and after
virtual resection in-silico revealed a slight increase, possibly reflecting the
effect of resection-induced portal hyperperfusion. Comparing length-related
parameters between post-operative day 7 and after virtual resection showed
similar vascular growth in both vascular systems investigated. In contrast,
radius-related parameters increased slightly more in the portal vein. Despite the
seemingly homogeneous 3D growth, the observed vascular parameters were not
compatible with the hypothesis of isotropic expansion of liver parenchyma and
vascular structures. CONCLUSION: We present an approach for the quantitative
analysis of the vascular systems of regenerating mouse livers. We applied this
technique for assessing the hepatic growth pattern. Prospectively, this approach
can be used to investigate hepatic vascular regeneration under different
conditions.
PMID- 27494254
TI - A Primate APOL1 Variant That Kills Trypanosoma brucei gambiense.
AB - Humans are protected against infection from most African trypanosomes by
lipoprotein complexes present in serum that contain the trypanolytic pore-forming
protein, Apolipoprotein L1 (APOL1). The human-infective trypanosomes, Trypanosoma
brucei rhodesiense in East Africa and T. b. gambiense in West Africa have
separately evolved mechanisms that allow them to resist APOL1-mediated lysis and
cause human African trypanosomiasis, or sleeping sickness, in man. Recently,
APOL1 variants were identified from a subset of Old World monkeys, that are able
to lyse East African T. b. rhodesiense, by virtue of C-terminal polymorphisms in
the APOL1 protein that hinder that parasite's resistance mechanism. Such variants
have been proposed as candidates for developing therapeutic alternatives to the
unsatisfactory anti-trypanosomal drugs currently in use. Here we demonstrate the
in vitro lytic ability of serum and purified recombinant protein of an APOL1
ortholog from the West African Guinea baboon (Papio papio), which is able to lyse
examples of all sub-species of T. brucei including T. b. gambiense group 1
parasites, the most common agent of human African trypanosomiasis. The
identification of a variant of APOL1 with trypanolytic ability for both human
infective T. brucei sub-species could be a candidate for universal APOL1-based
therapeutic strategies, targeted against all pathogenic African trypanosomes.
PMID- 27494256
TI - Is hepatic oxidative stress a main driver of dietary selenium toxicity in white
sturgeon (Acipenser transmontanus)?
AB - Most species of sturgeon have experienced significant population declines and
poor recruitment over the past decades, leading many, including white sturgeon
(Acipenser transmontanus), to be listed as endangered. Reasons for these declines
are not yet fully understood but benthic lifestyle, longevity, and delayed sexual
maturation likely render sturgeon particularly susceptible to factors such as
habitat alteration and contaminant exposures. One contaminant of particular
concern to white sturgeon is selenium (Se), especially in its more bioavailable
form selenomethionine (SeMet), as it is known to efficiently bioaccumulate in
prey items of this species. Studies have shown white sturgeon to be among the
most sensitive species of fish to dietary SeMet as well as other pollutants such
as metals, dioxin-like chemicals and endocrine disrupters. One of the primary
hypothesized mechanisms of toxicity of SeMet in fish is oxidative stress;
however, little is know about the specific mode by which SeMet affects the health
of white sturgeon. Therefore, the aim of this study was to characterize oxidative
stress and associated antioxidant responses as a molecular event of toxicity, and
to link it with the pathological effects observed previously. Specifically, three
year-old white sturgeon were exposed for 72 days via their diet to 1.4, 5.6, 22.4
or 104.4ug Se per g feed (dm). Doses were chosen to range over a necessary Se
intake level, current environmentally relevant intakes and an intake representing
predicted increases of Se release. Lipid hydroperoxides, which are end products
of lipid oxidation, were quantified as a marker of oxidative stress. Changes in
gene expression of glutathione peroxidase (GPx), superoxide dismutase, catalase,
glutathione S-transferase, apoptosis inducing factor and caspase 3 were
quantified as markers of the response to oxidative stress. Concentrations of
lipid hydroperoxides were highly variable within dose groups and no dose response
was observed. GPx expression was significantly increased in the low dose group
indicating an induced antioxidant response. Expression of other genes were not
significantly induced or suppressed. Overall, there was very little evidence of
oxidative stress, and therefore, in contrast to previous reports on other species
of teleost fishes, oxidative stress is not believed to be a main driver of
toxicity in white sturgeon exposed to SeMet.
PMID- 27494258
TI - NIAS-Server: Neighbors Influence of Amino acids and Secondary Structures in
Proteins.
AB - The exponential growth in the number of experimentally determined three
dimensional protein structures provide a new and relevant knowledge about the
conformation of amino acids in proteins. Only a few of probability densities of
amino acids are publicly available for use in structure validation and prediction
methods. NIAS (Neighbors Influence of Amino acids and Secondary structures) is a
web-based tool used to extract information about conformational preferences of
amino acid residues and secondary structures in experimental-determined protein
templates. This information is useful, for example, to characterize folds and
local motifs in proteins, molecular folding, and can help the solution of complex
problems such as protein structure prediction, protein design, among others. The
NIAS-Server and supplementary data are available at http://sbcb.inf.ufrgs.br/nias
.
PMID- 27494257
TI - When Does Return of Voluntary Finger Extension Occur Post-Stroke? A Prospective
Cohort Study.
AB - OBJECTIVES: Patients without voluntary finger extension early post-stroke are
suggested to have a poor prognosis for regaining upper limb capacity at 6 months.
Despite this poor prognosis, a number of patients do regain upper limb capacity.
We aimed to determine the time window for return of voluntary finger extension
during motor recovery and identify clinical characteristics of patients who,
despite an initially poor prognosis, show upper limb capacity at 6 months post
stroke. METHODS: Survival analysis was used to assess the time window for return
of voluntary finger extension (Fugl-Meyer Assessment hand sub item finger
extension>=1). A cut-off of >=10 points on the Action Research Arm Test was used
to define return of some upper limb capacity (i.e. ability to pick up a small
object). Probabilities for regaining upper limb capacity at 6 months post-stroke
were determined with multivariable logistic regression analysis using patient
characteristics. RESULTS: 45 of the 100 patients without voluntary finger
extension at 8 +/- 4 days post-stroke achieved an Action Research Arm Test score
of >=10 points at 6 months. The median time for regaining voluntary finger
extension for these recoverers was 4 weeks (lower and upper percentile
respectively 2 and 8 weeks). The median time to return of VFE was not reached for
the whole group (N = 100). Patients who had moderate to good lower limb function
(Motricity Index leg>=35 points), no visuospatial neglect (single-letter
cancellation test asymmetry between the contralesional and ipsilesional sides of
<2 omissions) and sufficient somatosensory function (Erasmus MC modified
Nottingham Sensory Assessment>=33 points) had a 0.94 probability of regaining
upper limb capacity at 6 months post-stroke. CONCLUSIONS: We recommend weekly
monitoring of voluntary finger extension within the first 4 weeks post-stroke and
preferably up to 8 weeks. Patients with paresis mainly restricted to the upper
limb, no visuospatial neglect and sufficient somatosensory function are likely to
show at least some return of upper limb capacity at 6 months post-stroke.
PMID- 27494259
TI - Fast isotopic separation of 10 B and 11 B boric acid by capillary zone
electrophoresis.
AB - Fast isotopic separation of 10 B and 11 B boric acid by CZE was demonstrated. The
BGE contained 25 mM phenylalanine and 5 mM putrescine (rN 8.95). The running
conditions were +25 kV at 20 degrees C with indirect photometric detection at 210
nm. Baseline separation was achieved in less than 9 min. RSD of migration times
and corrected peak areas were less than 0.5 and 3%, respectively (n = 5).
Linearity was demonstrated in the range 0.2-2 mM for 11 B and 0.2-0.5 mM for 10
B.
PMID- 27494260
TI - Comparison of immune persistence among inactivated and live attenuated hepatitis
a vaccines 2 years after a single dose.
AB - OBJECTIVE: Compare immune persistence from one dose of each of 3 different
hepatitis A vaccines when given to school-age children: a domestic, live
attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A
vaccine (Healive(r)); and an imported, inactivated hepatitis A vaccine
(Havrix(r)),. METHODS: School-age children were randomized into 1 of 4 groups to
receive a single dose of a vaccine: H2 vaccine, Healive(r), Havrix(r), or
hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months
after vaccination for measurement of anti-HAV IgG using microparticle enzyme
immunoassay. Seropositivity was defined as >= 20 mUI/ml. We compared groups on
seropositivity and geometric mean concentration (GMC). RESULTS: Seropositive
rates for the H2, Healive(r), Havrix(r), and control groups were 64%, 94.4%, 73%,
and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and
1.0%, respectively 24-months post-vaccination. Seropositivity was greater for
Healive(r) than for H2 and Havrix(r) at 12 months (p-values < 0.001) and 24
months (p-values < 0.0001). Average GMCs for the H2, Healive(r), Havrix(r), and
control groups, in mIU/ml, were 29.7, 81.0, 36.4, and 2.9, respectively at 12
months, and 30.9, 112.2, 44.3, and 2.9, respectively, at 24 months. GMCs were
greater for Healive(r) than for H2 and Havrix(r) at 12 months (p-values < 0.0001
and < 0.001, respectively) and 24 months (p-values < 0.001). No statistically
significant differences in seropositivity or GMC were found within groups between
12 and 24 months. CONCLUSION: Immunity persisted 24 months after a single dose of
inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine.
PMID- 27494261
TI - Successful emotion regulation requires both conviction and skill: beliefs about
the controllability of emotions, reappraisal, and regulation success.
AB - To succeed in self-regulation, people need to believe that it is possible to
change behaviour and they also need to use effective means to enable such a
change. We propose that this also applies to emotion regulation. In two studies,
we found that people were most successful in emotion regulation, the more they
believed emotions can be controlled and the more they used an effective emotion
regulation strategy - namely, cognitive reappraisal. Cognitive reappraisal
moderated the link between beliefs about the controllability of emotion and
success in emotion regulation, when reappraisal was measured as a trait (Study 1)
or manipulated (Study 2). Such moderation was found when examining the regulation
of disgust elicited by emotion-inducing films (Study 1), and the regulation of
anger elicited by real political events (Study 2). We discuss the implications of
our findings for research and practice in emotion regulation.
PMID- 27494262
TI - Vibrational Effects on Electron Momentum Distributions of Outer-Valence Orbitals
of Oxetane.
AB - Vibrational effects on electron momentum distributions (EMDs) of outer-valence
orbitals of oxetane are computed with a comprehensive consideration of all
vibrational modes. It is found that vibrational motions influence EMDs of all
outer-valence orbitals noticeably. The agreement between theoretical and
experimental momentum profiles of the first five orbitals is greatly improved
when including molecular vibrations in the calculation. In particular, the large
turn-up at low momentum in the experimental momentum profile of the 3b1 orbital
is well interpreted by vibrational effects, indicating that, besides the low
frequency ring-puckering mode, C-H stretching motion also plays a significant
role in affecting EMDs of outer-valence orbitals of oxetane. The case of oxetane
exhibits the significance of checking vibrational effects when performing
electron momentum spectroscopy measurements.
PMID- 27494263
TI - Medical therapy to prevent recurrence of ventricular arrhythmia in normal and
structural heart disease patients.
AB - INTRODUCTION: Recurrent ventricular arrhythmias (VA) are a source of significant
morbidity in patients without structural heart disease (SHD) and also mortality
in patients with SHD. The treatment goals for these two patient populations
differ greatly. Areas covered: The secondary prevention of recurrent VA in
patients without and with SHD will be reviewed, focusing on clinical data
(especially randomized, controlled trials) in the literature as determined
through searches in PubMed and ClinicalTrials.gov. This will include beta
blockers, non-dihydropyridine calcium channel blockers and antiarrhythmic drugs
in both subgroups and non-antiarrhythmic medications in SHD. Expert commentary:
The available options for medical therapy for VA in both normal hearts and SHD
are insufficient, due to substandard efficacy and toxicities. While non
pharmacologic therapies may provide an excellent option, further drug development
and randomized trials are needed, as is a reappraisal of the current mode of
utilization.
PMID- 27494265
TI - Erratum.
PMID- 27494264
TI - Zirconium-Based Metal-Organic Framework for Removal of Perrhenate from Water.
AB - The efficient removal of pertechnetate (TcO4(-)) anions from liquid waste or
melter off-gas solution for an alternative treatment is one of the promising
options to manage (99)Tc in legacy nuclear waste. Safe immobilization of (99)Tc
is of major importance because of its long half-life (t1/2 = 2.13 * 10(5) yrs)
and environmental mobility. Different types of inorganic and solid-state ion
exchange materials have been shown to absorb TcO4(-) anions from water. However,
both high capacity and selectivity have yet to be achieved in a single material.
Herein, we show that a protonated version of an ultrastable zirconium-based metal
organic framework can adsorb perrhenate (ReO4(-)) anions, a nonradioactive
surrogate for TcO4(-), from water even in the presence of other common anions.
Synchrotron-based powder X-ray diffraction and molecular simulations were used to
identify the position of the adsorbed ReO4(-) (surrogate for TcO4(-)) molecule
within the framework.
PMID- 27494266
TI - Variation of DNA Methylome of Zebrafish Cells under Cold Pressure.
AB - DNA methylation is an essential epigenetic mechanism involved in multiple
biological processes. However, the relationship between DNA methylation and cold
acclimation remains poorly understood. In this study, Methylated DNA
Immunoprecipitation Sequencing (MeDIP-seq) was performed to reveal a genome-wide
methylation profile of zebrafish (Danio rerio) embryonic fibroblast cells (ZF4)
and its variation under cold pressure. MeDIP-seq assay was conducted with ZF4
cells cultured at appropriate temperature of 28 degrees C and at low temperature
of 18 degrees C for 5 (short-term) and 30 (long-term) days, respectively. Our
data showed that DNA methylation level of whole genome increased after a short
term cold exposure and decreased after a long-term cold exposure. It is
interesting that metabolism of folate pathway is significantly hypomethylated
after short-term cold exposure, which is consistent with the increased DNA
methylation level. 21% of methylation peaks were significantly altered after cold
treatment. About 8% of altered DNA methylation peaks are located in promoter
regions, while the majority of them are located in non-coding regions.
Methylation of genes involved in multiple cold responsive biological processes
were significantly affected, such as anti-oxidant system, apoptosis, development,
chromatin modifying and immune system suggesting that those processes are
responsive to cold stress through regulation of DNA methylation. Our data
indicate the involvement of DNA methylation in cellular response to cold
pressure, and put a new insight into the genome-wide epigenetic regulation under
cold pressure.
PMID- 27494267
TI - A shift in coronary care unit patient population: Ten year experience from an
urban tertiary care center.
AB - The need for cardiovascular expertise in the treatment of advanced heart failure
(AHF), malignant arrhythmias, and structural heart disease has shifted the role
of the CCU to a more diverse and medically complex patient population. This
study's purpose was to analyze the temporal trends in the principal diagnosis
leading to admission to the CCU in a tertiary referral hospital. Over the last 15
years, the CCU has evolved from a medical unit strictly focusing on the care of
patients with ACS to an advanced cardiac intensive care unit. The trends observed
at our center provide further evidence that today's CCU contains a broader, more
complex, critically-ill patient population.
PMID- 27494268
TI - A new approach for estimating the density of liquids.
AB - We propose a novel approach with which to estimate the density of liquids. The
approach is based on the assumption that the systems would be structurally
similar when viewed at around the length scale (inverse wavenumber) of the first
peak of the structure factor, unless their thermodynamic states differ
significantly. The assumption was implemented via a similarity transformation to
the radial distribution function to extract the density from the structure factor
of a reference state with a known density. The method was first tested using two
model liquids, and could predict the densities within an error of several percent
unless the state in question differed significantly from the reference state. The
method was then applied to related real liquids, and satisfactory results were
obtained for predicted densities. The possibility of applying the method to
amorphous materials is discussed.
PMID- 27494269
TI - Correlation between electrical and hemodynamic responses during visual
stimulation with graded contrasts.
AB - Brain functional activity involves complex cellular, metabolic, and vascular
chain reactions, making it difficult to comprehend. Electroencephalography (EEG)
and functional near infrared spectroscopy (fNIRS) have been combined into a
multimodal neuroimaging method that captures both electrophysiological and
hemodynamic information to explore the spatiotemporal characteristics of brain
activity. Because of the significance of visually evoked functional activity in
clinical applications, numerous studies have explored the amplitude of the visual
evoked potential (VEP) to clarify its relationship with the hemodynamic response.
However, relatively few studies have investigated the influence of latency, which
has been frequently used to diagnose visual diseases, on the hemodynamic
response. Moreover, because the latency and the amplitude of VEPs have different
roles in coding visual information, investigating the relationship between
latency and the hemodynamic response should be helpful. In this study,
checkerboard reversal tasks with graded contrasts were used to evoke visual
functional activity. Both EEG and fNIRS were employed to investigate the
relationship between neuronal electrophysiological activities and the hemodynamic
responses. The VEP amplitudes were linearly correlated with the hemodynamic
response, but the VEP latency showed a negative linear correlation with the
hemodynamic response.
PMID- 27494271
TI - High Energy Density All Solid State Asymmetric Pseudocapacitors Based on Free
Standing Reduced Graphene Oxide-Co3O4 Composite Aerogel Electrodes.
AB - Modern flexible consumer electronics require efficient energy storage devices
with flexible free-standing electrodes. We report a simple and cost-effective
route to a graphene-based composite aerogel encapsulating metal oxide
nanoparticles for high energy density, free-standing, binder-free flexible
pseudocapacitive electrodes. Hydrothermally synthesized Co3O4 nanoparticles are
successfully housed inside the microporous graphene aerogel network during the
room temperature interfacial gelation at the Zn surface. The resultant three
dimensional (3D) rGO-Co3O4 composite aerogel shows mesoporous quasiparallel layer
stack morphology with a high loading of Co3O4, which offers numerous channels for
ion transport and a 3D interconnected network for high electrical conductivity.
All solid state asymmetric pseudocapacitors employing the composite aerogel
electrodes have demonstrated high areal energy density of 35.92 MUWh/cm(2) and
power density of 17.79 mW/cm(2) accompanied by excellent cycle life.
PMID- 27494270
TI - A four-week team-rehabilitation programme in a warm climate decreases disability
and improves health and body function for up to one year: A prospective study in
Swedish patients with inflammatory joint diseases.
AB - OBJECTIVE: In the era of biologics, we evaluated the short- and long-term effects
of team-rehabilitation in a warm climate in patients with arthritis and an
inadequate response to physio-therapy in Sweden. METHODS: A total of 161 patients
with peripheral arthritis and spondyloarthritis, 63% treated with biologics,
followed team-rehabilitation for a period of 4 weeks. The outcomes assessed pre-
and post-rehabilitation and after 3 and 12 months covered the Heath Assessment
Questionnaire (HAQ), Bath Ankylosing Spondylitis Functional Index (BASFI),
EuroQoL 5-Dimensions (EQ-5D), general health (VAS-GH), pain (VAS-pain) and the
International Physical Activity Questionnaire. RESULTS: HAQ, VAS-GH and VAS-pain
improved significantly from pre-rehabilitation to all follow-up time-points, and
BASFI and EQ-5D up to 3 months. In patients treated with biologics, the results
were similar. At 3 and 12 months the proportions of patients reporting
improvement above the minimal clinically important difference were HAQ 62% and
35%, BASFI 73% and 61%, EQ-5D 47% and 39%, VAS-GH 68% and 52%, and VAS-pain 68%
and 51%, respectively. Physical activity increased significantly from pre
rehabilitation to 12 months and this increase correlated with an improvement in
EQ-5D (r = 0.20, p = 0.040). CONCLUSION: Team-rehabilitation in a warm climate
resulted in clinically meaningful improvements in body function, activities and
well-being, and promoted physical activity for up to one year.
PMID- 27494272
TI - Efficacy of tip cryotherapy in the treatment of idiopathic guttate hypomelanosis
(IGH): a randomized, controlled, evaluator-blinded study.
AB - BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a common hypopigmentation
affecting a large amount of older population. However, there is no standard
treatment. Cryotherapy has been reported as an alternative therapy for years;
nevertheless, there is no randomized controlled study to determine its efficacy.
OBJECTIVES: To evaluate the efficacy and side effects of tip cryotherapy in IGH
treatment. MATERIAL AND METHODS: Total 101 lesions were included. Forty-three
lesions were treated with cryotherapy and 58 lesions were assigned as control. A
single session of tip cryotherapy was delivered and remained for 5 s. Colorimeter
was used to measure lesional luminosity at baseline and then monthly until 4
months. Digital photographs were evaluated by two blinded dermatologists. In
addition, patients' assessments and side effects were assessed. RESULTS: Mean
luminosity scale gradually decreased from baseline. Also, the score of the
treated lesions has been significantly lower than that of the control lesions
since week 8 (p = .005). At the fourth month, dermatologists' assessment revealed
that 82.3% of the treated lesions comparing to only 2% of the control showed more
than 75% improvement (p < .001). Burning sensation was the most common side
effect. CONCLUSION: Tip cryotherapy appears to be an effective therapy with
minimal adverse effect for IGH.
PMID- 27494273
TI - Nanopillar Arrayed Triboelectric Nanogenerator as a Self-Powered Sensitive Sensor
for a Sleep Monitoring System.
AB - A flexible and low-cost triboelectric nanogenerator (TENG) based on a patterned
aluminum-plastic film and an entrapped cantilever spring leaf is developed as a
self-powered sensitive triboelectric sensor for sleep-body movement monitoring.
The working mechanism and the impact factors of electric output performance were
systematically investigated and elaborated. Due to the patterned nanostructures
of the recently designed TENG, both the output voltage and current are greatly
enhanced, and thereby the sensitivity of the device is significantly improved.
The self-powered and sensitive device has been demonstrated as a smart body
motion sensor of sleep monitoring for diagnosis of sleep disorders due to its
high sensitivity and excellent stability. This work may promote the application
of self-powered TENGs for healthcare and be helpful for the development of real
time mobile healthcare services and smart external portable electronics.
PMID- 27494276
TI - Finite Systems in a Heat Bath: Spectrum Perturbations and Thermodynamics.
AB - When a finite system is at equilibrium with a heat bath, the equilibrium
temperature is dictated by the heat bath and not by the intrinsic
thermostatistics of the finite system. If not sufficiently large, it may be
necessary for the finite system to change its thermostatistics in order to be at
equilibrium with the heat bath. We account for this process by invoking
Landsberg's notion of temperature-dependent energy levels. We establish that the
mismatch between the intrinsic temperature of the excited finite system and that
of the heat bath drives a spectrum perturbation which enables thermal
equilibrium. We show that the temperature-induced spectrum perturbation is
equivalent to Hill's purely thermodynamic subdivision potential. The difference
between intrinsic and equilibrium temperature provides us with a measure for how
large a system can be before it no longer needs to be regarded as small. The
theoretical framework proposed in this paper identifies the role of temperature
in a bottom-up thermostatistical description of finite systems.
PMID- 27494274
TI - Coupling between the DEAD-box RNA helicases Ded1p and eIF4A.
AB - Eukaryotic translation initiation involves two conserved DEAD-box RNA helicases,
eIF4A and Ded1p. Here we show that S. cerevisiae eIF4A and Ded1p directly
interact with each other and simultaneously with the scaffolding protein eIF4G.
We delineate a comprehensive thermodynamic framework for the interactions between
Ded1p, eIF4A, eIF4G, RNA and ATP, which indicates that eIF4A, with and without
eIF4G, acts as a modulator for activity and substrate preferences of Ded1p, which
is the RNA remodeling unit in all complexes. Our results reveal and characterize
an unexpected interdependence between the two RNA helicases and eIF4G, and
suggest that Ded1p is an integral part of eIF4F, the complex comprising eIF4G,
eIF4A, and eIF4E.
PMID- 27494277
TI - Monitoring CO2 invasion processes at the pore scale using geological labs on
chip.
AB - In order to investigate at the pore scale the mechanisms involved during CO2
injection in a water saturated pore network, a series of displacement experiments
is reported using high pressure micromodels (geological labs on chip - GLoCs)
working under real geological conditions (25 < T ( degrees C) < 75 and 4.5 < p
(MPa) < 8). The experiments were focused on the influence of three experimental
parameters: (i) the p, T conditions, (ii) the injection flow rates and (iii) the
pore network characteristics. By using on-chip optical characterization and
imaging approaches, the CO2 saturation curves as a function of either time or the
number of pore volume injected were determined. Three main mechanisms were
observed during CO2 injection, namely, invasion, percolation and drying, which
are discussed in this paper. Interestingly, besides conventional mechanisms, two
counterintuitive situations were observed during the invasion and drying
processes.
PMID- 27494275
TI - Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca(2+)
signalling in glutamatergic interneurons.
AB - Neuronal circuits are known to integrate nutritional information, but the
identity of the circuit components is not completely understood. Amino acids are
a class of nutrients that are vital for the growth and function of an organism.
Here, we report a neuronal circuit that allows Drosophila larvae to overcome
amino acid deprivation and pupariate. We find that nutrient stress is sensed by
the class IV multidendritic cholinergic neurons. Through live calcium imaging
experiments, we show that these cholinergic stimuli are conveyed to glutamatergic
neurons in the ventral ganglion through mAChR. We further show that IP3R
dependent calcium transients in the glutamatergic neurons convey this signal to
downstream medial neurosecretory cells (mNSCs). The circuit ultimately converges
at the ring gland and regulates expression of ecdysteroid biosynthetic genes.
Activity in this circuit is thus likely to be an adaptation that provides a layer
of regulation to help surpass nutritional stress during development.
PMID- 27494278
TI - Dual Emission and Mechanofluorochromism of a V-Shaped pi-System Composed of
Disulfonyl-Substituted Dibenzocyclooctatetraenes.
AB - A series of dibenzocyclooctatetraenes 6 bearing phenylethynyl and phenylsulfonyl
groups were synthesized from bromo-substituted formylbenzyl sulfone 4 via cyclic
dimerization of 4 and Sonogashira coupling of the resulting
dibromocyclooctatetraene 3 with terminal acetylenes. The diamino derivative 6b
exhibited dual emission with emission maxima at 436 and 547 nm. Furthermore, in
the fluorescence of 6b, solvatofluorochromism was observed in response to solvent
polarity, whereas in the solid states, mechanofluorochromism was observed.
PMID- 27494279
TI - Positron range in tissue-equivalent materials: experimental microPET studies.
AB - In this work an experimental investigation was carried out to study the effect
that positron range has over positron emission tomography (PET) scans through
measurements of the line spread function (LSF) in tissue-equivalent materials.
Line-sources consisted of thin capillary tubes filled with (18)F, (13)N or (68)Ga
water-solution inserted along the axis of symmetry of cylindrical phantoms
constructed with the tissue-equivalent materials: lung (inhale and exhale),
adipose tissue, solid water, trabecular and cortical bone. PET scans were
performed with a commercial small-animal PET scanner and image reconstruction was
carried out with filtered-backprojection. Line-source distributions were analyzed
using radial profiles taken on axial slices from which the spatial resolution was
determined through the full-width at half-maximum, tenth-maximum, twentieth
maximum and fiftieth-maximum. A double-Gaussian model of the LSFs was used to fit
experimental data which can be incorporated into iterative reconstruction
methods. In addition, the maximum activity concentration in the line-sources was
determined from reconstructed images and compared to the known values for each
case. The experimental data indicates that positron range in different materials
has a strong effect on both spatial resolution and activity concentration
quantification in PET scans. Consequently, extra care should be taken when
computing standard-uptake values in PET scans, in particular when the
radiopharmaceutical is taken up by different tissues in the body, and more even
so with high-energy positron emitters.
PMID- 27494280
TI - Identification and discrimination of three common Aloe species by high
performance liquid chromatography-tandem mass spectrometry coupled with
multivariate analysis.
AB - Aloe arborescens, Aloe barbadensis and Aloe ferox are the most widely cultivated
and used among 500 aloe species due to their potent bioactivity. However, the
difference of aloe species is neglected and labeled only one name Aloe in the
market without specifying aloe species discrimination in general. Furthermore,
differences in bioactivity and side effects from different aloe species have not
been well investigated. This study develops an effective method for simultaneous
qualitative and quantitative determination of three common aloe species using
high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and
high performance liquid chromatography-diode array detection (HPLC-DAD). The
extraction conditions were optimized by response surface methodology (RSM) based
on methanol concentration, extraction time and solvent-to-material ratio. A
partial least squares-discriminant analysis (PLS-DA) was used to identify the
three aloe species. The developed HPLC-MS/MS method coupled with multivariate
analysis can be applied to discriminate three aloe species successfully.
PMID- 27494281
TI - Pharmacokinetic studies of novel berberine derivatives with ultra-performance
liquid chromatography-tandem mass spectrometry.
AB - An ultra-performance liquid chromatography with tandem mass spectrometric
detection method was developed for the detection of berberine and its derivatives
(A4, B4) in rat plasma and other organs. This validated method was successfully
applied to our pharmacokinetic study of BBR derivatives in rats. At the same dose
of administration, the Cmax of B4 was about eight times higher than BBR, and its
half-life was approximately two times longer than BBR, according to the bigger
areas under plasma concentration curves. Inversely, the pharmacokinetic parameter
levels of A4 were all inferior to BBR, suggesting a tight structure-activity
relationship of these compounds. Small dose of parenteral administration was used
for the study of absolute oral bioavailability of A4, B4, and BBR, and the
results calculated were 0.12%, 3.4% and 0.7%, respectively. The accumulations of
B4 among all organs were intestine>liver>heart>kidney>lung>spleen>plasma, proving
a deeply targeting property of B4, which met our experimental assumption.
Together, the experimental results proved that compared with BBR and A4, the
derivative B4 had higher absolute oral bioavailability and the ability of deeply
targeting so that can be likely used in some organ-targeted diseases.
PMID- 27494283
TI - Influence of sp(3)-sp(2) Carbon Nanodomains on Metal/Support Interaction,
Catalyst Durability, and Catalytic Activity for the Oxygen Reduction Reaction.
AB - In this work, platinum nanoparticles were impregnated by two different
techniques, namely the carbonyl chemical route and photodeposition, onto
systematically surface-modified multiwalled carbon nanotubes. The different
interactions between platinum nanoparticles with sp(2)-sp(3) carbon nanodomains
were investigated. The oxidation of an adsorbed monolayer of carbon monoxide,
used to probe electronic catalytic modification, suggests a selective nucleation
of platinum nanoparticles onto sp(2) carbon nanodomains when photodeposition
synthesis is carried out. XPS attests the catalytic center electronic
modification obtained by photodeposition. DFT calculations were used to determine
the interaction energy of a Pt cluster with sp(2) and sp(3) carbon surfaces as
well as with oxidized ones. The interaction energy and electronic structure of
the platinum cluster presents dramatic changes as a function of the support
surface chemistry, which also modifies its catalytic properties evaluated by the
interaction with CO. The interaction energy was calculated to be 8-fold higher on
sp(3) and oxidized surfaces in comparison to sp(2) domains. Accelerated Stability
Test (AST) was applied only on the electronic-modified materials to evaluate the
active phase degradation and their activity toward oxygen reduction reaction
(ORR). The stability of photodeposited materials is correlated with the surface
chemical nature of supports indicating that platinum nanoparticles supported onto
multiwalled carbon nanotubes with the highest sp(2) character show the higher
stability and activity toward ORR.
PMID- 27494282
TI - Neural Activity during Voluntary Movements in Each Body Representation of the
Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex.
AB - In order to accurately interpret experimental data using the topographic body map
identified by conventional intracortical microstimulation (ICMS), it is important
to know how neurons in each division of the map respond during voluntary
movements. Here we systematically investigated neuronal responses in each body
representation of the ICMS map during a reach-grasp-retrieval task that involves
the movements of multiple body parts. The topographic body map in the primary
motor cortex (M1) generally corresponds to functional divisions of voluntary
movements; neurons at the recording sites in each body representation with
movement thresholds of 10 MUA or less were differentially activated during the
task, and the timing of responses was consistent with the movements of the body
part represented. Moreover, neurons in the digit representation responded
differently for the different types of grasping. In addition, the present study
showed that neural activity depends on the ICMS current threshold required to
elicit body movements and the location of the recording on the cortical surface.
In the ventral premotor cortex (PMv), no correlation was found between the
response properties of neurons and the body representation in the ICMS map.
Neural responses specific to forelimb movements were often observed in the
rostral part of PMv, including the lateral bank of the lower arcuate limb, in
which ICMS up to 100 MUA evoked no detectable movement. These results indicate
that the physiological significance of the ICMS-derived maps is different
between, and even within, areas M1 and PMv.
PMID- 27494284
TI - Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among
Primary Care Physicians in Israel.
AB - BACKGROUND: Osteoporosis is a systemic skeletal disorder characterized by
impaired bone quality and microstructural deterioration leading to an increased
propensity to fractures. This is a major health problem for older adults, which
comprise an increasingly greater proportion of the general population. Due to a
large number of patients and the insufficient availability of specialists in
Israel and worldwide, osteoporosis is treated in large part by primary care
physicians. We assessed the knowledge of primary care physicians on the diagnosis
and treatment of osteoporosis. METHODS: Physician's knowledge, sources of
knowledge acquisition and self-evaluation of knowledge were assessed using a
multiple choice questionnaire. Professional and demographic characteristics were
assessed as well. RESULTS: Of 490 physicians attending a conference, 363 filled
the questionnaires (74% response rate). The physicians demonstrated better
expertise in diagnosis than in medications (mechanism of action, side effects or
contra-indications) but less than for other treatment related decisions. Overall,
50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51%
were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3%
were aware that bisphosphonates should be avoided in patients with impaired renal
function. Respondents stated frontal lectures at meetings as their main source of
information on the subject. CONCLUSION: The study indicates the need to intensify
efforts to improve the knowledge of primary care physicians regarding
osteoporosis, in general; and osteoporosis pharmacotherapy, in particular.
PMID- 27494285
TI - Two-Dimensional Inorganic Cationic Network of Thorium Iodate Chloride with Unique
Halogen-Halogen Bonds.
AB - A unique two-dimensional inorganic cationic network with the formula
[Th3O2(IO3)5(OH)2]Cl was synthesized hydrothermally. Its crystal structure can
best be described as positively charged slabs built with hexanuclear thorium
clusters connected by iodate trigonal pyramids. Additional chloride anions are
present in the interlayer spaces but surprisingly are not exchangeable, as
demonstrated by a series of CrO4(2-) uptake experiments. This is because all
chloride anions are trapped by multiple strong halogen-halogen interactions with
short Cl-I bond lengths ranging from 3.134 to 3.333 A, forming a special Cl
centered trigonal-pyramidal polyhedron as a newly observed coordination mode for
halogen bonds. Density functional theory calculations clarified that electrons
transformed from central Cl atoms to I atoms, generating a halogen-halogen
interaction energy with a value of about -8.3 kcal mol(-1) per Cl...I pair as
well as providing a total value of -57.9 kcal mol(-1) among delocalized halogen
halogen bonds, which is a new record value reported for a single halogen atom.
Additional hydrogen-bonding interaction is also present between Cl and OH, and
the interaction energy is predicted to be -8.1 kcal mol(-1), confirming the
strong total interaction to lock the interlayer Cl anions.
PMID- 27494287
TI - Assessing for Unilateral Spatial Neglect Using Eye-Tracking Glasses: A
Feasibility Study.
AB - The aim of this feasibility study was to identify whether eye-tracking glasses
could sensitively differentiate unilateral spatial neglect (USN) among a sample
of participants who had a stroke, and to determine whether a larger study was
viable. A sample of 13 inpatients (N = 7 with neglect, N = 6 without neglect)
aged 50-78 years undertook a task while wearing Tobii eye-tracking glasses. The
kitchen environment and the task of making a cup of coffee were standardized. Two
commonly reported tests for USN, the Bells Test and the Line Crossing Test, were
also used as a reference standard for the eye-tracking data. Participants with
USN spent significantly more time searching on the right-hand side (p = .006) for
items during the task than those without neglect. There was a moderate
correlation between eye-tracking data and the Bells Test (r = .622, p = .04).
Overall, this study supported the feasibility of using a real-life task with eye
tracking to detect neglect.
PMID- 27494286
TI - Imaging Evaluation of Malignant Chest Wall Neoplasms.
AB - Neoplasms of the chest wall are uncommon lesions that represent approximately 5%
of all thoracic malignancies. These tumors comprise a heterogeneous group of
neoplasms that may arise from osseous structures or soft tissues, and they may be
malignant or benign. More than 50% of chest wall neoplasms are malignancies and
include tumors that may arise as primary malignancies or secondarily involve the
chest wall by way of direct invasion or metastasis from intrathoracic or
extrathoracic neoplasms. Although 20% of chest wall tumors may be detected at
chest radiography, chest wall malignancies are best evaluated with cross
sectional imaging, principally multidetector computed tomography (CT) and
magnetic resonance (MR) imaging, each of which has distinct strengths and
limitations. Multidetector CT is optimal for depicting bone, muscle, and vascular
structures, whereas MR imaging renders superior soft-tissue contrast and spatial
resolution and is better for delineating the full extent of disease. Fluorine 18
fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT is not routinely
performed to evaluate chest wall malignancies. The primary functions of PET/CT in
this setting include staging of disease, evaluation of treatment response, and
detection of recurrent disease. Ultrasonography has a limited role in the
evaluation and characterization of superficial chest wall lesions; however, it
can be used to guide biopsy and has been shown to depict chest wall invasion by
lung cancer more accurately than CT. It is important that radiologists be able to
identify the key multidetector CT and MR imaging features that can be used to
differentiate malignant from benign chest lesions, suggest specific histologic
tumor types, and ultimately guide patient treatment. ((c))RSNA, 2016.
PMID- 27494288
TI - Formation of delta-Lactones by Cerium-Catalyzed, Baeyer-Villiger-Type Coupling of
beta-Oxoesters, Enol Acetates, and Dioxygen.
AB - Formation of delta-lactones is observed when cyclopentanone-2-carboxylates are
converted in a cerium-catalyzed reaction with alpha-aryl vinyl acetates under
oxidative conditions. The products of this transformation possess a 1,4
dicarbonyl constitution together with a quaternary carbon center. Atmospheric
oxygen is the oxidant in this process, which can be regarded as ideal from
economic and ecological points of view. Further advantages of this new C-C
coupling and oxidation reaction are its operational simplicity and the
application of nontoxic and inexpensive CeCl3.7 H2O as precatalyst. This so far
unprecedented reaction is proposed to proceed via 1,2-dioxane derivatives, which
decompose under formation of an oxycarbenium cation in a Baeyer-Villiger-type
pathway. This mechanistic picture is supported by the observation that electron
rich (donor substituted or heteroaromatic) enol esters give higher yields than
electron deficient congeners. Apart from 1,4-diketones and alpha-hydroxylated
beta-oxoesters formed as byproducts, the yields of delta-lactones range from
moderate to good (up to 74%).
PMID- 27494289
TI - Investigating the Influence of Polymers on Supersaturated Flufenamic Acid
Cocrystal Solutions.
AB - The development of enabling formulations is a key stage when demonstrating the
effectiveness of pharmaceutical cocrystals to maximize the oral bioavailability
for poorly water soluble drugs. Inhibition of drug crystallization from a
supersaturated cocrystal solution through a fundamental understanding of the
nucleation and crystal growth is important. In this study, the influence of the
three polymers of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), and a
copolymer of N-vinly-2-pyrrodidone (60%) and vinyl acetate (40%) (PVP-VA) on the
flufenamic acid (FFA) crystallization from three different supersaturated
solutions of the pure FFA and two cocrystals of FFA-NIC CO and FFA-TP CO has been
investigated by measuring nucleation induction times and desupersaturation rates
in the presence and absence of seed crystals. It was found that the competition
of intermolecular hydrogen bonding among drug/coformer, drug/polymer, and
coformer/polymer was a key factor responsible for maintaining supersaturation
through nucleation inhibition and crystal growth modification in a cocrystal
solution. The supersaturated cocrystal solutions with predissolved PEG
demonstrated more effective stabilization in comparison to the pure FFA in the
presence of the same polymer. In contrast, neither of the two cocrystal
solutions, in the presence of PVP or PVP-VA, exhibited a better performance than
the pure FFA with the same predissolved polymer. The study suggests that the
selection of a polymeric excipient in a cocrystal formulation should not be
solely dependent on the interplay of the parent drug and polymer without
considering the coformer effects.
PMID- 27494290
TI - Historical record of nuclear activities from 129I in corals from the northern
hemisphere (Philippines).
AB - Iodine-129 is a long-lived fission product that is majorly released in human
nuclear activities (HNA) such as nuclear bomb testing, nuclear fuel reprocessing,
and nuclear accidents. It is a good environmental tracer and former measurements
of 129I in corals from the southern hemisphere show the increasing trend of 129I
concentrations in the marine environment caused by HNA. Here we show time series
of 129I/127(stable)I isotopic ratios in two coral cores from the northern
hemisphere (Philippines) and how these record 129I released from HNA in even
greater, unprecedented detail. Corals were taken from the Pacific Ocean (Baler)
and South China Sea (Parola) sides of the Philippines. We observed nearly
identical peaks (129I/127I ~ 31.5 * 10-12) in both the Baler and Parola records,
each attributed to the year 1962 - the year with the highest recorded amount of
129I release from nuclear bomb testing. This 1962 129I bomb signal offers a new
time marker that can be used to establish or confirm age models of corals,
comparable to or possibly better than the well-known coral 14C bomb peak. We also
observed nuclear fuel reprocessing and Chernobyl accident 129I signals in years
1977, 1980, and 1986, concurrently in Parola and with 9 to 11-year lags in Baler.
This discrepancy in timing suggests that 129I was transported to the South China
Sea and Pacific Ocean sides of the Philippines directly from the atmosphere and
through prevailing ocean currents, respectively. Lastly, we observed surprisingly
high 129I/127I isotopic ratios (i.e., 22.8 to 38.9 * 10-12) in the Parola record
after the year 1996, which is in contrast to the decreasing trend observed in the
Baler record and in published 129I releases of different HNA. These results
possibly indicate the presence of unknown sources of 129I in the South China Sea
region.
PMID- 27494291
TI - Ionizer induced 220Rn decay product removal in confined environment: Continuous
vs. instantaneous source.
AB - This paper presents an experimental approach to evaluate the effectiveness of
unipolar ionizers in indoor environment for the removal of thoron (220Rn)
daughter products. Both continuous and instantaneous source conditions were
simulated during these experiments. Activity and aerosol related parameters were
measured for these experiments and results were interpreted. Activity
concentration was found to be reduced by a factor 6.6 and 34 for continuous and
instantaneous source conditions, respectively. The particle size dependency of
mitigation of particles using ionizer is also discussed. The effect of ionizer on
activity size distribution has been directly measured for the first time. The
ionizer induced changes in particle size distributions were coupled to Dose
Reduction Factor (DRF) model and significant DRF values were obtained for both
source conditions. This study discusses open issues which are important for
establishing ionizer induced radioactivity mitigation as a technology
application.
PMID- 27494292
TI - The spatio-temporal specificity of PYR1/PYL/RCAR ABA receptors in response to
developmental and environmental cues.
AB - From the different functions ABA exerted between the aboveground and belowground,
seed and vegetative tissues, primary root and lateral root, stimulating stomatal
closure and inhibiting stomatal opening, between young and senescence leaves in
stomatal movement, among different cells in plasma membrane water permeability,
we addressed the organ-, tissue-, cell-, physiological processes-, and
development stage specificities of PYR1/PYL/RCAR ABA receptors. This specificity
may reflect the spatio-temporal properties of water potentials as well as the
endogenous ABA levels in detail context, which plus the various affinities among
this receptor families, resulted in the specificity of the transcripts as well as
genes functions. PYR1/PYL/RCAR ABA receptors may integrate the message of ABA
resource (local signaling or long distance signaling) and concentration, thus
fine-tuning ABA response to environmental- and developmental cues. It also
evolutionally affording land plants sophisticated mechanism to survival adverse
environments.
PMID- 27494293
TI - Effects of dispersal and selection on stochastic assembly in microbial
communities.
AB - Stochastic processes can play an important role in microbial community assembly.
Dispersal limitation is one process that can increase stochasticity and obscure
relationships between environmental variables and microbial community
composition, but the relationship between dispersal, selection and stochasticity
has not been described in a comprehensive way. We examine how dispersal and its
interactions with drift and selection alter the consistency with which microbial
communities assemble using a realistic, individual-based model of microbial
decomposers. Communities were assembled under different environmental conditions
and dispersal rates in repeated simulations, and we examined the compositional
difference among replicate communities colonizing the same type of leaf litter
('within-group distance'), as well as between-group deterministic selection.
Dispersal rates below 25% turnover per year resulted in high within-group
distance among communities and no significant environmental effects. As dispersal
limitation was alleviated, both within- and between-group distance decreased, but
despite this homogenization, deterministic environmental effects remained
significant. In addition to direct effects of dispersal rate, stochasticity of
community composition was influenced by an interaction between dispersal and
selection strength. Specifically, communities experiencing stronger selection
(less favorable litter chemistries) were more stochastic, possibly because lower
biomass and richness intensified drift or priority effects. Overall, we show that
dispersal rate can significantly alter patterns of community composition.
Partitioning the effects of dispersal, selection and drift based on static
patterns of microbial composition will be difficult, if not impossible.
Experiments will be required to tease apart these complex interactions between
assembly processes shaping microbial communities.
PMID- 27494294
TI - Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo
Pharmacokinetics of Dibenzo[def,p]chrysene and Metabolites by UPLC Accelerator
Mass Spectrometry.
AB - Metabolism is a key health risk factor following exposures to pro-carcinogenic
polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an
IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs
primarily from the diet in nonsmokers. However, little data is available on the
metabolism and pharmacokinetics in humans of high molecular weight PAHs (>=4
aromatic rings), including DBC. We previously determined the pharmacokinetics of
DBC in human volunteers orally administered a microdose (29 ng; 5 nCi) of [14C]
DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and
urine. In the current study, we utilized a novel "moving wire" interface between
ultraperformance liquid chromatography (UPLC) and AMS to detect and quantify
parent DBC and its major metabolites. The major [14C] product identified in
plasma was unmetabolized [14C]-DBC itself (Cmax = 18.5 +/-15.9 fg/mL, Tmax= 2.1
+/- 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12
diol (Cmax= 2.5 +/-1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC
metabolites were also detected for which no reference standards were available.
Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC
11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which
were conjugated (Cmax= 35.8 +/- 23.0 pg/pool, Tmax = 6-12 h pool). [14C]-DBC
11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax =
29.4 +/- 11.6 pg/pool, Tmax = 6-12 h pool). Parent [14C]-DBC was not detected in
urine. This is the first data set to assess metabolite profiles and associated
pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally
relevant dose, providing the data necessary for translation of high dose animal
models to humans for translation of environmental health risk assessment.
PMID- 27494295
TI - Time-resolved homo-FRET studies of biotin-streptavidin complexes.
AB - Forster resonance energy transfer is a mechanism of fluorescence quenching that
is notably useful for characterizing properties of biomolecules and/or their
interactions. Here we study water-solutions of Biotin-Streptavidin complexes, in
which Biotin is labeled with a rigidly-bound fluorophore that can interact by
Forster resonance energy transfer with the fluorophores labeling the other, up to
three, Biotins of the same complex. The fluorophore, Atto550, is a Rhodamine
analogue. We detect the time-resolved fluorescence decay of the fluorophores with
an apparatus endowed with single-photon sensitivity and temporal resolution of
~30ps. The decay profiles we observe for samples containing constant Biotin
Atto550 conjugates and varying Streptavidin concentrations are multi-exponential.
Each decay component can be associated with the rate of quenching exerted on each
donor by each of the acceptors that label the other Biotin molecules, depending
on the binding site they occupy. The main features that lead to this result are
that (i) the transition dipole moments of the up-to-four Atto550 fluorophores
that label the complexes are fixed as to both relative positions and mutual
orientations; (ii) the fluorophores are identical and the role of donor in each
Biotin-Streptavidin complex is randomly attributed to the one that has absorbed
the excitation light (homo-FRET). Obviously the high-temporal resolution of the
excitation-detection apparatus is necessary to discriminate among the
fluorescence decay components.
PMID- 27494296
TI - ClustENM: ENM-Based Sampling of Essential Conformational Space at Full Atomic
Resolution.
AB - Accurate sampling of conformational space and, in particular, the transitions
between functional substates has been a challenge in molecular dynamic (MD)
simulations of large biomolecular systems. We developed an Elastic Network Model
(ENM)-based computational method, ClustENM, for sampling large conformational
changes of biomolecules with various sizes and oligomerization states. ClustENM
is an iterative method that combines ENM with energy minimization and clustering
steps. It is an unbiased technique, which requires only an initial structure as
input, and no information about the target conformation. To test the performance
of ClustENM, we applied it to six biomolecular systems: adenylate kinase (AK),
calmodulin, p38 MAP kinase, HIV-1 reverse transcriptase (RT), triosephosphate
isomerase (TIM), and the 70S ribosomal complex. The generated ensembles of
conformers determined at atomic resolution show good agreement with experimental
data (979 structures resolved by X-ray and/or NMR) and encompass the subspaces
covered in independent MD simulations for TIM, p38, and RT. ClustENM emerges as a
computationally efficient tool for characterizing the conformational space of
large systems at atomic detail, in addition to generating a representative
ensemble of conformers that can be advantageously used in simulating
substrate/ligand-binding events.
PMID- 27494298
TI - Bioherbicidal activity of a germacranolide sesquiterpene dilactone from Ambrosia
artemisiifolia L.
AB - Ambrosia artemisiifolia L. (common ragweed) is an invasive plant whose
allelopathic properties have been suggested by its field behaviour and
demonstrated through phytotoxicity bioassays. However, the nature of the
molecules responsible for the allelopathic activity of common ragweed has not
been explored. The main objective of this study was to identify the phytotoxic
molecules produced by A. artemisiifolia. A preliminary investigation has
indicated that a methanol extract of A. artemisiifolia completely inhibited the
germination of cress and radish. Semi-preparative fractionation of the methanol
extract allowed separating of phytotoxic fraction which contained a single
compound. The structure of this compound was elucidated by liquid chromatography
mass spectrometry (LC-MS)/MS, high-resolution mass spectral, nuclear magnetic
resonance, and Fourier transform infrared spectra as sesquiterpene lactone
isabelin (C15H16O4). The effect of pure isabelin was tested on four different
weed species, confirming the inhibitory activity of molecule. The results
indicate directions for the future studies about herbicidal specific activity of
isabelin, as pure molecule or in the crude extract, as a potential candidate for
biological weed control.
PMID- 27494297
TI - Cell type specific DNA methylation in cord blood: A 450K-reference data set and
cell count-based validation of estimated cell type composition.
AB - Epigenome-wide association studies of prenatal exposure to different
environmental factors are becoming increasingly common. These studies are usually
performed in umbilical cord blood. Since blood comprises multiple cell types with
specific DNA methylation patterns, confounding caused by cellular heterogeneity
is a major concern. This can be adjusted for using reference data consisting of
DNA methylation signatures in cell types isolated from blood. However, the most
commonly used reference data set is based on blood samples from adult males and
is not representative of the cell type composition in neonatal cord blood. The
aim of this study was to generate a reference data set from cord blood to enable
correct adjustment of the cell type composition in samples collected at birth.
The purity of the isolated cell types was very high for all samples (>97.1%), and
clustering analyses showed distinct grouping of the cell types according to
hematopoietic lineage. We explored whether this cord blood and the adult
peripheral blood reference data sets impact the estimation of cell type
composition in cord blood samples from an independent birth cohort (MoBa, n =
1092). This revealed significant differences for all cell types. Importantly,
comparison of the cell type estimates against matched cell counts both in the
cord blood reference samples (n = 11) and in another independent birth cohort
(Generation R, n = 195), demonstrated moderate to high correlation of the data.
This is the first cord blood reference data set with a comprehensive examination
of the downstream application of the data through validation of estimated cell
types against matched cell counts.
PMID- 27494299
TI - Early intervention with tafamidis provides long-term (5.5-year) delay of
neurologic progression in transthyretin hereditary amyloid polyneuropathy.
AB - : Transthyretin hereditary amyloid polyneuropathy, also traditionally known as
transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless,
fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific
transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy
progression in early-stage ATTRV30M-FAP in a 1.5-year, randomized, double-blind,
placebo-controlled trial, and 1-year open-label extension study, with a second
long-term open-label extension study ongoing. Subgroup analysis of the
effectiveness of tafamidis in the pivotal study and its open-label extensions
revealed a relatively cohesive cohort of patients with mild neuropathy (i.e.
Neuropathy Impairment Score for Lower Limbs [NIS-LL] <= 10) at the start of
active treatment. Early treatment with tafamidis for up to 5.5 years (>=1 dose of
tafamidis meglumine 20 mg once daily during the original trial or after switching
from placebo in its extension) resulted in sustained delay in neurologic
progression and long-term preservation of nutritional status in this cohort. Mean
(95% CI) changes from baseline in NIS-LL and mBMI were 5.3 (1.6, 9.1) points and
7.8 (-44.3, 28.8) kg/m2 * g/L at 5.5 years, respectively. No new safety issues or
side effects were identified. These data represent the longest prospective
evaluation of tafamidis to date, confirm a favorable safety profile, and
underscore the long-term benefits of early intervention with tafamidis. TRIAL
REGISTRATION: ClincalTrials.gov Identifier: NCT00409175, NCT00791492, and
NCT00925002.
PMID- 27494300
TI - Regulation of platelet membrane protein shedding in health and disease.
AB - Extracellular proteolysis of platelet plasma membrane proteins is an event that
ensues platelet activation. Shedding of surface receptors such as glycoprotein
(GP) Ibalpha, GPV and GPVI as well as externalized proteins P-selectin and CD40L
releases soluble ectodomain fragments that are subsequently detectable in plasma.
This results in the irreversible functional downregulation of platelet receptor
mediated adhesive interactions and the generation of biologically active
fragments. In this review, we describe molecular insights into the regulation of
platelet receptor and ligand shedding in health and disease. The scope of this
review is specially focused on GPIbalpha, GPV, GPVI, P-selectin and CD40L where
we: (1) describe the basic physiological regulation of expression and shedding of
these proteins in hemostasis illustrate alterations in receptor expression during
(2) apoptosis and (3) ex vivo storage relevant for blood banking purposes; (4)
discuss considerations to be made when analyzing and interpreting shedding of
platelet membrane proteins and finally; (5) collate clinical evidence that
quantify these platelet proteins during disease.
PMID- 27494301
TI - Community-acquired hyperkalemia in elderly patients: risk factors and clinical
outcomes.
AB - BACKGROUND: Although the risk and related factors of hyperkalemia developed in
the hospital are known in elderly, risk and related factors of community-acquired
hyperkalemia (CAH) in this population are not well known. This study was
performed to investigate the risk of CAH in elderly and evaluate the related
factors and clinical outcomes. Study design, setting and participants,
intervention: Patients (aged >=65 years) with hyperkalemia were screened. Group 1
(young-old); 65-74 years/old, Group 2 (middle-old); 75-84 years/old, Group 3
(oldest-old); >=85 years/old, and Group 4 (control group); >=65 years/old (normal
serum potassium levels). The relation between CAH and hospital expenses (HE), the
number of comorbid diseases (NCD), and all-cause of mortality rates (MR) were
evaluated. We also investigated whether drugs, sex, and NCD are risk factors for
the development of CAH. RESULTS: There was a positive correlation between serum
potassium levels and length of hospital stay, MR, HE, and NCD (p < 0.001). Risk
factors for CAH were the use of non-steroidal-anti inflammatory drugs (NSAIDs)
(Odds Ratio [OR]: 2.679), spironolactone (OR: 2.530), and angiotensin converting
enzyme inhibitors (ACEI) (OR: 2.242), angiotensin receptor blockers (ARB) (OR:
2.679), >=2 comorbid diseases (OR: 2.221), female gender (OR: 2.112), and renal
injury (OR: 5.55). CAH risk was found to be increased 30.03 times when any of
ACEI, ARB, NSAIDs, or spironolactone is given to a patient with a renal injury.
CONCLUSION: Use of NSAIDs, ACEI, ARB, spironolactone and increased NCD are all
independent risk factors for CAH in the elderly, especially in patients with
kidney diseases.
PMID- 27494302
TI - Drug repurposing: a new front in the war against Staphylococcus aureus.
AB - Staphylococcus aureus continues its domination of worldwide bacterial infection
rates, thereby remaining a pathogen of significant public health interest. A
major reason for its continued success is its ability to acquire and maintain
diverse drug resistance mechanisms, leading to a paucity of antimicrobials active
against it, concomitantly leading to a continuous search for new antimicrobial
agents. However, with the withdrawal of the major pharmaceutical firms from the
anti-infective area, drug repurposing has provided a potential boost to the drug
pipeline. In this review, we provide an overview of the currently approved drugs
with repurposing potential against Staphylococcus aureus, thus augmenting the
classical drug discovery pathway.
PMID- 27494304
TI - The effect of dual tasking on foot kinematics in people with functional ankle
instability.
AB - BACKGROUND: Some cases of repeated inversion ankle sprains are thought to have a
neurological basis and are termed functional ankle instability (FAI). In addition
to factors local to the ankle, such as loss of proprioception, cognitive demands
have the ability to influence motor control and may increase the risk of
repetitive lateral sprains. OBJECTIVE: The purpose of this study was to
investigate the effect of cognitive demand on foot kinematics in physically
active people with functional ankle instability. METHODS: 21 physically active
participants with FAI and 19 matched healthy controls completed trials of normal
walking (single task) and normal walking while performing a cognitive task (dual
task). Foot motion relative to the shank was recorded. Cognitive performance,
ankle kinematics and movement variability in single and dual task conditions was
characterized. RESULTS: During normal walking, the ankle joint was significantly
more inverted in FAI compared to the control group pre and post initial contact.
Under dual task conditions, there was a statistically significant increase in
frontal plane foot movement variability during the period 200ms pre and post
initial contact in people with FAI compared to the control group (p<0.05). Dual
task also significantly increased plantar flexion and inversion during the period
200ms pre and post initial contact in the FAI group (p<0.05). CONCLUSION:
participants with FAI demonstrated different ankle movement patterns and
increased movement variability during a dual task condition. Cognitive load may
increase risk of ankle instability in these people.
PMID- 27494305
TI - Mobile inertial sensor based gait analysis: Validity and reliability of
spatiotemporal gait characteristics in healthy seniors.
AB - Gait analysis is commonly used to identify gait changes and fall risk in clinical
populations and seniors. Body-worn inertial sensor based gait analyses provide a
feasible alternative to optometric and pressure based measurements of
spatiotemporal gait characteristics. We assessed validity and relative and
absolute reliability of a body-worn inertial sensor system (RehaGait((r))) for
measuring spatiotemporal gait characteristics compared to a standard stationary
treadmill (Zebris((r))). Spatiotemporal gait parameters (walking speed, stride
length, cadence and stride time) were collected for 24 healthy seniors (age:
75.3+/-6.7 years) tested on 2 days (1 week apart) simultaneously using the sensor
based system and instrumented treadmill. Each participant completed walking tests
(200 strides) at different walking speeds and slopes. The difference between the
RehaGait((r)) system and the treadmill was trivial (Cohen's d<0.2) except for
speed and stride length at slow speed (Cohen's d, 0.35 and 0.49, respectively).
Intraclass correlation coefficients (ICC) were excellent for temporal gait
characteristics (cadence and stride time; ICC: 0.99-1.00) and moderate for stride
length (ICC: 0.73-0.89). Both devices had excellent day-to-day reliability for
all gait parameters (ICC: 0.82-0.99) except for stride length at slow speed (ICC:
0.74). The RehaGait((r)) is a valid and reliable tool for assessing
spatiotemporal gait parameters for treadmill walking at different speeds and
slopes.
PMID- 27494303
TI - Hypoxia-Inducible Factor-1alpha Regulates CD55 in Airway Epithelium.
AB - Airway epithelial CD55 down-regulation occurs in several hypoxia-associated
pulmonary diseases, but the mechanism is unknown. Using in vivo and in vitro
assays of pharmacologic inhibition and gene silencing, the current study
investigated the role of hypoxia-inducible factor (HIF)-1alpha in regulating
airway epithelial CD55 expression. Hypoxia down-regulated CD55 expression on
small-airway epithelial cells in vitro, and in murine lungs in vivo; the latter
was associated with local complement activation. Treatment with pharmacologic
inhibition or silencing of HIF-1alpha during hypoxia-recovered CD55 expression in
small-airway epithelial cells. HIF-1alpha overexpression or blockade, in vitro or
in vivo, down-regulated CD55 expression. Collectively, these data show a key role
for HIF-1alpha in regulating the expression of CD55 on airway epithelium.
PMID- 27494306
TI - Facile Preparation of Stable Antibody-Gold Conjugates and Application to Affinity
Capture Self-Interaction Nanoparticle Spectroscopy.
AB - Protein-nanoparticle conjugates are widely used for conventional applications
such as immunohistochemistry and biomolecular detection as well as emerging
applications such as therapeutics and advanced materials. Nevertheless, it
remains challenging to reproducibly prepare stable protein-nanoparticle
conjugates with highly similar optical properties. Here we report an improved
physisorption method for reproducibly preparing stable antibody-gold conjugates
at acidic pH using polyclonal antibodies from a wide range of species (human,
goat, rabbit, mouse, and rat). We find that gold particles synthesized using
citrate alone or in combination with tannic acid are similar in size but display
variable colloidal stability when conjugated to polyclonal antibodies. The
variability in conjugate stability is due to differences in the pH and
composition of the original gold colloid, which prevents reproducible preparation
of stable antibody conjugates without additional purification of the particles
prior to conjugation. Sedimentation-based purification of gold particles
synthesized using different methods enabled reproducible generation of antibody
gold conjugates with high stability and similar plasmon wavelengths. We also find
that antibody conjugates prepared using our improved procedure display excellent
performance when applied to a high-throughput immunogold assay (affinity-capture
self-interaction nanoparticle spectroscopy, AC-SINS) for identifying monoclonal
antibodies with low self-association, high solubility, and low viscosity. The
stable antibody conjugates prepared with various types of gold colloid result in
robust and reproducible AC-SINS measurements of antibody self-association using
extremely dilute (microgram per mL) and unpurified antibody solutions. We expect
that this improved methodology will be useful for reproducibly preparing stable
antibody-gold conjugates for diverse applications.
PMID- 27494309
TI - An Evaluation Tool for Agricultural Health and Safety Mobile Applications.
AB - As the use of mobile devices and their software applications, or apps, becomes
ubiquitous, use amongst agricultural working populations is expanding as well.
The smart device paired with a well-designed app has potential for improving
workplace health and safety in the hands of those who can act upon the
information provided. Many apps designed to assess workplace hazards and
implementation of worker protections already exist. However, the abundance and
diversity of such applications also presents challenges regarding evaluation
practices and assignation of value. This is particularly true in the agricultural
workspace, as there is currently little information on the value of these apps
for agricultural safety and health. This project proposes a framework for
developing and evaluating apps that have potential usefulness in agricultural
health and safety. The evaluation framework is easily transferable, with little
modification for evaluation of apps in several agriculture-specific areas.
PMID- 27494310
TI - Significance of Pharmacogenetics and Pharmacogenomics Research in Current Medical
Practice.
AB - Human genome sequencing highlights the involvement of genetic variation towards
differential risk of human diseases, presence of different phenotypes, and
response to pharmacological elements. This brings the field of personalized
medicine to forefront in the era of modern health care. Numerous recent
approaches have shown that how variation in the genome at single nucleotide level
can be used in pharmacological research. The two broad aspects that deal with
pharmacological research are pharmacogenetics and pharmacogenomics. This review
encompasses how these variations have created the basis of pharmacogenetics and
pharmacogenomics research and important milestones accomplished in these two
fields in different diseases. It further discusses at length their importance in
disease diagnosis, response of drugs, and various treatment modalities on the
basis of genetic determinants.
PMID- 27494308
TI - Examination of the association of sex and race/ethnicity with appearance
concerns: a Scleroderma Patient-centered Intervention Network (SPIN) Cohort
study.
AB - OBJECTIVES: Appearance concerns are common in systemic sclerosis (SSc) and have
been linked to younger age and more severe disease. No study has examined their
association with sex or race/ethnicity. METHODS: SSc patients were sampled from
the Scleroderma Patient-centered Intervention Network Cohort. Presence of
appearance concerns was assessed with a single item, and medical and
sociodemographic information were collected. RESULTS: Of 644 patients, appearance
concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men
(53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified
as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In
multivariate analysis, women had significantly greater odds of reporting
appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval
(CI)=1.78-4.95, p<.001). Black patients had significantly greater odds of
appearance concerns than White patients in unadjusted (OR=2.64, 95% CI=1.01-6.34,
p=.030), but not multivariate analysis (OR=1.76, 95% CI=0.67-4.60, p=.250).
Compared to a general population sample, appearance concerns were substantially
more common in SSc, particularly for men across all age groups and for younger
women. The most commonly reported features of concern were related to the face
and head, followed by the hands and fingers; this did not differ by sex or
race/ethnicity. CONCLUSIONS: Appearance concerns were common in SSc. Women were
substantially more likely than men to have appearance concerns. Although non
significant in multivariate analysis, Black patients were more likely to have
concerns than White patients, likely due to more severe changes in appearance.
PMID- 27494311
TI - Influence of silver nanoparticles on heavy metals of pore water in contaminated
river sediments.
AB - Despite the increasing knowledge on the discharge of silver nanoparticles (AgNPs)
into the environment and their potential toxicity to microorganisms, the
interaction of AgNPs with heavy metals remains poorly understood. This study
focused on the effect of AgNPs on heavy metal concentration and form in sediment
contaminated with heavy metals from the Xiangjiang River. The results showed that
the concentration of Cu, Zn, Pb and Cd decreased and then increased with a change
in form. The changes in form and concentrations of heavy metals in pore water
suggested that Cu and Zn were more likely to be affected compared to Pb and Cd.
The concentrations of Hg in sediment pore water in three AgNPs-dosed containers,
increased greatly until they reached their peaks at 4.468 +/- 0.133, 4.589 +/-
0.235, and 5.083 +/- 0.084 MUg L(-1) in Bare AgNPs, Citrate AgNPs and Tween 80
AgNPs, respectively. The measurements of Hg concentrations in the sediment pore
water, combined with SEM and EDX analysis, demonstrated that added AgNPs
stabilized in pore water and formed an amalgam with Hg(0), which can affect Hg
transportation over long distance.
PMID- 27494312
TI - Toluene removal by sequential adsorption-plasma catalytic process: Effects of Ag
and Mn impregnation sequence on Ag-Mn/gamma-Al2O3.
AB - A series of Ag-Mn/gamma-Al2O3 were prepared under different Ag/Mn impregnation
sequence and tested in the sequential adsorption-plasma catalytic removal of
toluene. When Mn was impregnated first, the resulting catalyst, Ag-Mn(F)/gamma
Al2O3, had longer breakthrough time, gave less emission of toluene, had higher
CO2 selectivity, and had better carbon balance and COx yield compared to
catalysts prepared via other impregnation sequences. After 120 min of NTP
treatment, the carbon balance of Ag-Mn(F)/gamma-Al2O3 was 91%, with 87% as COx
contributions. A Brunauer-Emmett-Teller (BET) analysis and X-ray photoelectron
spectroscopy (XPS) results show that, the impregnation sequence impacts the BET
surface area and the ratio and existing state of Ag on the surface of the
catalysts. The longer breakthrough time when using Ag-Mn(F)/gamma-Al2O3 as
catalyst is attributed to the large amount of Ag(+) on the surface. Ag(+) is a
new active site for toluene adsorption. When Ag was impregnated first (Ag(F)
Mn/gamma-Al2O3) or Ag and Mn co-impregnated (Ag-Mn-C/gamma-Al2O3), the
predominant specie was Ag(+). Both Ag(0) and Ag(+) species were detected on Ag
Mn(F)/gamma-Al2O3. Ag(0) cooperation with MnOx may promote the migration of
surface active oxygen. This would facilitate the oxidation of adsorbed toluene
with CC bond already weakened by Ag(+) and would result in higher CO2 selectivity
and better carbon balance as seen in the Ag-Mn(F)/gamma-Al2O3 system.
PMID- 27494313
TI - Microbial toxicity of ionic species leached from the II-VI semiconductor
materials, cadmium telluride (CdTe) and cadmium selenide (CdSe).
AB - This work investigated the microbial toxicity of soluble species that can
potentially be leached from the II-VI semiconductor materials, cadmium telluride
and cadmium selenide. The soluble ions tested included: cadmium, selenite,
selenate, tellurite, and tellurate. Their toxicity towards the acetoclastic and
hydrogen-consuming trophic groups in a methanogenic consortium as well as towards
a bioluminescent marine bacterium, Aliivibrio fischeri (Microtox((r)) test), was
assessed. The acetoclastic methanogenic activity was the most affected as
evidenced by the low 50% inhibiting concentrations (IC50) values obtained of 8.6
mg L(-1) for both cadmium and tellurite, 10.2 mg L(-1) for tellurate, and 24.1 mg
L(-1) for selenite. Both tellurium oxyanions caused a strong inhibition of
acetoclastic methanogenesis at low concentrations, each additional increment in
concentration provided progressively less inhibition increase. In the case of the
hydrogenotrophic methanogenesis, cadmium followed by selenite caused the greatest
inhibition with IC50 values of 2.9 and 18.0 mg L(-1), respectively. Tellurite
caused a moderate effect as evidenced by a 36.8% inhibition of the methanogenic
activity at the highest concentration tested, and a very mild effect of tellurate
was observed. Microtox((r)) analyses showed a noteworthy inhibition of cadmium,
selenite, and tellurite with 50% loss in bioluminescence after 30 min of exposure
of 5.5, 171.1, and 458.6 mg L(-1), respectively. These results suggest that the
leaching of cadmium, tellurium and selenium ions from semiconductor materials can
potentially cause microbial toxicity.
PMID- 27494314
TI - Enhanced stable long-term operation of biotrickling filters treating VOCs by low
dose ozonation and its affecting mechanism on biofilm.
AB - For long-term operation of highly loaded biotrickling filters (BTFs), the
prevention of excess biomass accumulation was essential for avoiding BTF failure.
In this study, we proposed low-dose ozonation as a biomass control strategy to
maintain high removal efficiencies of volatile organic compounds (VOCs) over
extended operation of BTFs. To obtain an optimized biomass control strategy, the
relative performance of five parallel BTFs receiving different ozone doses was
determined, and the affecting mechanism of ozonation on biofilm was elucidated.
Experimental results showed that the decline in ozone-free BTF performance began
from day 150, which was correlated with excess biomass accumulation, abundant
excretion of extracellular polymeric substances (EPS) and a decline in metabolic
activity of biofilm over extended operation. Ozone of 5-10 mg m(-3) was effective
in preventing excessive growth and uneven distribution of biomass, and eventually
maintaining long-term stable operations. Ozone of over 20 mg m(-3) possibly
inhibited microorganism growth severely, thereby deteriorating the elimination
performance instead. Comparison of the biofilm EPS indicated that the presence of
ozone reduce EPS contents to different extents, which was possibly beneficial for
mass transfer and metabolic activity. Comparative community analysis showed that
ozonation resulted in different microbial communities in the BTFs. Dyella was
found to be the most abundant bacterial genera in all BTFs regardless of
ozonation, indicating strong resistance to ozonation. Chryseobacterium and
Burkholderia members were markedly enriched in the ozone-added biofilm, implying
good adaptation to ozone presence. These findings provided an improved
understanding of low-dose ozonation in maintaining a stable long-term operation
of BTF.
PMID- 27494315
TI - Studies on organic and in-organic biostimulants in bioremediation of diesel
contaminated arable soil.
AB - In this study, use of inorganic fertilizer (N.P.K) was compared with organic
manure (compost) in the bioremediation of diesel-polluted agricultural soil over
a two-month period. Renewal by enhanced natural attenuation was used as control.
The results revealed that total petroleum hydrocarbon removal from polluted soil
was 71.40 +/- 5.60% and 93.31 +/- 3.60% for N.P.K and compost amended options,
respectively. The control (natural attenuation) had 57.90 +/- 3.98% of total
petroleum hydrocarbon removed. Experimental data fitted second order kinetic
model adequately for compost amended option. The fertilizer amended option was
found to be 1.04 times slower (k2 = 4.00 +/- 1.40 * 10(-7)gmg(-1)d(-1), half-life
= 28.15 d) than compost amended option (k2 = 1.39 +/- 0.54 * 10(-5) gmg(-1)d(-1),
half-life = 8.10 d) but 1.21 times (20.6%) faster than the control (k2 = 2.57 +/-
0.16 * 10(-7) gmg(-1)d(-1), half-life = 43.81 d). The hydrocarbon utilizers
isolated from the diesel contaminated soil were: Bacillus nealsoni, Micrococcus
luteus, Aspergillus awamori, and Fusarium proliferatum. The phytotoxicity test
showed that germination indices for natural attenuation (control), fertilizer
(NPK) and compost amended options were 34%, 56%, and 89%, respectively.
PMID- 27494316
TI - Degradation mechanisms of geosmin and 2-MIB during UV photolysis and UV/chlorine
reactions.
AB - We conducted chlorination, UV photolysis, and UV/chlorin reactions to investigate
the intermediate formation and degradation mechanisms of geosmin and 2
methylisoborneol (2-MIB) in water. Chlorination hardly removed geosmin and 2-MIB,
while the UV/chlorine reaction at 254 nm completely removed geosmin and 2-MIB
within 40 min and 1 h, respectively, with lesser removals of both compounds
during UV photolysis. The kinetics during both UV photolysis and UV/chlorine
reactions followed a pseudo first-order reaction. Chloroform was found as a
chlorinated intermediate during the UV/chlorine reaction of both geosmin and 2
MIB. The pH affected both the degradation and chloroform production during the
UV/chlorine reaction. The open ring and dehydration intermediates identified
during UV/chlorine reactions were 1,4-dimethyl-adamantane, and 1,3-dimethyl
adamantane from geosmin, 2-methylenebornane, and 2-methyl-2-bornene from 2-MIB,
respectively. Additionally, 2-methyl-3-pentanol, 2,4-dimethyl-1-heptene, 4-methyl
2-heptanone, and 1,1-dichloro-2,4-dimethyl-1-heptane were newly identified
intermediates from UV/chlorine reactions of both geosmin and 2-MIB. These
intermediates were degraded as the reaction progressed. We proposed possible
degradation pathways during the UV photolysis and UV/chlorine reactions of both
compounds using the identified intermediates.
PMID- 27494317
TI - Sorbent materials for rapid remediation of wash water during radiological event
relief.
AB - Procedures for removing harmful radiation from interior and exterior surfaces of
homes and businesses after a nuclear or radiological disaster may generate large
volumes of radiologically contaminated waste water. Rather than releasing this
waste water to potentially contaminate surrounding areas, it is preferable to
treat it onsite. Retention barrels are a viable option because of their
simplicity in preparation and availability of possible sorbent materials. This
study investigated the use of aluminosilicate clay minerals as sorbent materials
to retain (137)Cs, (85)Sr, and (152)Eu. Vermiculite strongly retained (137)Cs,
though other radionuclides displayed diminished affinity for the surface.
Montmorillonite exhibited increased affinity to sorb (85)Sr and (152)Eu in the
presence of higher concentrations of (137)Cs. To simulate flow within retention
barrels, vermiculite was mixed with sand and used in small-scale column
experiments. The GoldSim contaminate fate module was used to model breakthrough
and assess the feasibility of using clay minerals as sorbent materials in
retention barrels. The modeled radionuclide breakthrough profiles suggest that
vermiculite-sand and montmorillonite-sand filled barrels could be used for
treatment of contaminated water generated from field operations.
PMID- 27494319
TI - A Method for Non-Rigid Face Alignment via Combining Local and Holistic Matching.
AB - We propose a method for non-rigid face alignment which only needs a single
template, such as using a person's smile face to match his surprise face. First,
in order to be robust to outliers caused by complex geometric deformations, a new
local feature matching method called K Patch Pairs (K-PP) is proposed.
Specifically, inspired by the state-of-art similarity measure used in template
matching, K-PP is to find the mutual K nearest neighbors between two images. A
weight matrix is then presented to balance the similarity and the number of local
matching. Second, we proposed a modified Lucas-Kanade algorithm combined with
local matching constraint to solve the non-rigid face alignment, so that a
holistic face representation and local features can be jointly modeled in the
object function. Both the flexible ability of local matching and the robust
ability of holistic fitting are included in our method. Furthermore, we show that
the optimization problem can be efficiently solved by the inverse compositional
algorithm. Comparison results with conventional methods demonstrate our
superiority in terms of both accuracy and robustness.
PMID- 27494318
TI - Echoic Sensory Substitution Information in a Single Obstacle Circumvention Task.
AB - Accurate motor control is required when walking around obstacles in order to
avoid collisions. When vision is unavailable, sensory substitution can be used to
improve locomotion through the environment. Tactile sensory substitution devices
(SSDs) are electronic travel aids, some of which indicate the distance of an
obstacle using the rate of vibration of a transducer on the skin. We investigated
how accurately such an SSD guided navigation in an obstacle circumvention task.
Using an SSD, 12 blindfolded participants navigated around a single flat 0.6 x 2
m obstacle. A 3-dimensional Vicon motion capture system was used to quantify
various kinematic indices of human movement. Navigation performance under full
vision was used as a baseline for comparison. The obstacle position was varied
from trial to trial relative to the participant, being placed at two distances 25
cm to the left, right or directly ahead. Under SSD guidance, participants
navigated without collision in 93% of trials. No collisions occurred under visual
guidance. Buffer space (clearance between the obstacle and shoulder) was larger
by a factor of 2.1 with SSD guidance than with visual guidance, movement times
were longer by a factor of 9.4, and numbers of velocity corrections were larger
by a factor of 5 (all p<0.05). Participants passed the obstacle on the side
affording the most space in the majority of trials for both SSD and visual
guidance conditions. The results are consistent with the idea that SSD
information can be used to generate a protective envelope during locomotion in
order to avoid collisions when navigating around obstacles, and to pass on the
side of the obstacle affording the most space in the majority of trials.
PMID- 27494320
TI - Population Structure, Genetic Diversity and Molecular Marker-Trait Association
Analysis for High Temperature Stress Tolerance in Rice.
AB - Rice exhibits enormous genetic diversity, population structure and molecular
marker-traits associated with abiotic stress tolerance to high temperature
stress. A set of breeding lines and landraces representing 240 germplasm lines
were studied. Based on spikelet fertility percent under high temperature,
tolerant genotypes were broadly classified into four classes. Genetic diversity
indicated a moderate level of genetic base of the population for the trait
studied. Wright's F statistic estimates showed a deviation of Hardy-Weinberg
expectation in the population. The analysis of molecular variance revealed 25
percent variation between population, 61 percent among individuals and 14 percent
within individuals in the set. The STRUCTURE analysis categorized the entire
population into three sub-populations and suggested that most of the landraces in
each sub-population had a common primary ancestor with few admix individuals. The
composition of materials in the panel showed the presence of many QTLs
representing the entire genome for the expression of tolerance. The strongly
associated marker RM547 tagged with spikelet fertility under stress and the
markers like RM228, RM205, RM247, RM242, INDEL3 and RM314 indirectly controlling
the high temperature stress tolerance were detected through both mixed linear
model and general linear model TASSEL analysis. These markers can be deployed as
a resource for marker-assisted breeding program of high temperature stress
tolerance.
PMID- 27494321
TI - Genome-Wide Association Analyses in 128,266 Individuals Identifies New
Morningness and Sleep Duration Loci.
AB - Disrupted circadian rhythms and reduced sleep duration are associated with
several human diseases, particularly obesity and type 2 diabetes, but until
recently, little was known about the genetic factors influencing these heritable
traits. We performed genome-wide association studies of self-reported chronotype
(morning/evening person) and self-reported sleep duration in 128,266 white
British individuals from the UK Biobank study. Sixteen variants were associated
with chronotype (P<5x10-8), including variants near the known circadian rhythm
genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2
(1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has
previously been associated with iris function. We sought replication using self
reported data from 89,283 23andMe participants; thirteen of the chronotype
signals remained associated at P<5x10-8 on meta-analysis and eleven of these
reached P<0.05 in the same direction in the 23andMe study. We also replicated 9
additional variants identified when the 23andMe study was used as a discovery
GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration,
we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9,
3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2
(2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per
allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation
between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG =
0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian
Randomisation analyses, with limited power, provided no consistent evidence of
causal associations between BMI or type 2 diabetes and chronotype or sleep
duration. Our study brings the total number of loci associated with chronotype to
22 and with sleep duration to three, and provides new insights into the biology
of sleep and circadian rhythms in humans.
PMID- 27494322
TI - Cost-Effectiveness Analysis of 1-Year Treatment with Golimumab/Standard Care and
Standard Care Alone for Ulcerative Colitis in Poland.
AB - OBJECTIVE: The objective of this study was to assess the cost-effectiveness of
induction and maintenance treatment up to 1 year of ulcerative colitis with
golimumab/standard care and standard care alone in Poland. METHODS: A Markov
model was used to estimate the expected costs and effects of golimumab/standard
care and a standard care alone. For each treatment option the costs and quality
adjusted life years were calculated to estimate the incremental cost-utility
ratio. The analysis was performed from the perspective of the Polish public payer
and society over a 30-years time horizon. The clinical parameters were derived
mainly from the PURSUIT-SC and PURSUIT-M clinical trials. Different direct and
indirect costs and utility values were assigned to the various model health
states. RESULTS: The treatment of ulcerative colitis patients with
golimumab/standard care instead of a standard care alone resulted in 0.122
additional years of life with full health. The treatment with golimumab/standard
care was found to be more expensive than treatment with the standard care alone
from the public payer perspective and from social perspective. The incremental
cost-utility ratio of golimumab/standard care compared to the standard care alone
is estimated to be 391,252 PLN/QALY gained (93,155 ?/QALYG) from public payer
perspective and 374,377 PLN/QALY gained (89,137 ?/QALYG) from social perspective.
CONCLUSIONS: The biologic treatment of ulcerative colitis patients with
golimumab/standard care is more effective but also more costly compared with
standard care alone.
PMID- 27494323
TI - Leishmania donovani Utilize Sialic Acids for Binding and Phagocytosis in the
Macrophages through Selective Utilization of Siglecs and Impair the Innate Immune
Arm.
AB - BACKGROUND: Leishmania donovani, belonging to a unicellular protozoan parasite,
display the differential level of linkage-specific sialic acids on their surface.
Sialic acids binding immunoglobulin-like lectins (siglecs) are a class of
membrane-bound receptors present in the haematopoetic cell lineages interact with
the linkage-specific sialic acids. Here we aimed to explore the utilization of
sialic acids by Leishmania donovani for siglec-mediated binding, phagocytosis,
modulation of innate immune response and signaling pathways for establishment of
successful infection in the host. METHODOLOGY/PRINCIPLE FINDINGS: We have found
enhanced binding of high sialic acids containing virulent strains (AG83+Sias)
with siglec-1 and siglec-5 present on macrophages compared to sialidase treated
AG83+Sias (AG83-Sias) and low sialic acids-containing avirulent strain (UR6) by
flow cytometry. This specific receptor-ligand interaction between sialic acids
and siglecs were further confirmed by confocal microscopy. Sialic acids-siglec-1
mediated interaction of AG83+Sias with macrophages induced enhanced phagocytosis.
Additionally, sialic acids-siglec-5 interaction demonstrated reduced ROS, NO
generation and Th2 dominant cytokine response upon infection with AG83+Sias in
contrast to AG83-Sias and UR6. Sialic acids-siglecs binding also facilitated
multiplication of intracellular amastigotes. Moreover, AG83+Sias induced sialic
acids-siglec-5-mediated upregulation of host phosphatase SHP-1. Such sialic acids
siglec interaction was responsible for further downregulation of MAPKs (p38, ERK
and JNK) and PI3K/Akt pathways followed by the reduced translocation of p65
subunit of NF-kappabeta to the nucleus from cytosol in the downstream signaling
pathways. This sequence of events was reversed in AG83-Sias and UR6-infected
macrophages. Besides, siglec-knockdown macrophages also showed the reversal of
AG83+Sias infection-induced effector functions and downstream signaling events.
CONCLUSIONS/SIGNIFICANCES: Taken together, this study demonstrated that virulent
parasite (AG83+Sias) establish a unique sialic acids-mediated binding and
subsequent phagocytosis in the host cell through the selective exploitation of
siglec-1. Additionally, sialic acids-siglec-5 interaction altered the downstream
signaling pathways which contributed impairment of immune effector functions of
macrophages. To the best of our knowledge, this is a comprehensive report
describing sialic acids-siglec interactions and their role in facilitating uptake
of the virulent parasite within the host.
PMID- 27494325
TI - Contribution of dot-blot assay to the diagnosis and management of myositis: a
three-year practice at a university hospital centre.
AB - OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune
diseases with wide clinical spectrum that may lead to delayed diagnosis. The aim
of this study was to examine the impact of IIM-specific dot-blot assay on
diagnostic process of patients presenting with muscular or systemic symptoms
evocating of IIM. METHODS: We collected all the prescriptions of an IIM specific
dot-blot assay (8 autoantigens including Jo-1, PL-7, PL-12, SRP, Mi-2, Ku, PM/Scl
and Scl-70) over a 38-month period. RESULTS: 316 myositis dot-blot assays (MSD)
were performed in 274 patients (156 women, mean age 53+/-10.6 years) referring
for muscular and/or systemic symptoms suggesting IIM. The timing of dot
prescription through the diagnostic process was highly variable: without (35%),
concomitantly (16%) or after electromyographic studies (35%). Fifty-nine patients
(22%) had IIM according to Bohan and Peter's criteria. Among them, 29 (49%) had
positive dot (8 Jo-1, 6 PM-Scl, 5 PL-12, 5 SRP, 2 Mi-2, 2 PL-7 and 1 Ku). Various
other diagnoses were performed including 35 autoimmune disease or granulomatosis
(12%), 19 inflammatory rheumatic disease (7%), 16 non inflammatory muscular
disorders (6%), 10 drug-induced myalgia (4%), 11 infectious myositis (4%). Except
11 borderline SRP results and one transient PM-Scl, MSD was positive only in one
case of IIM. Dot allowed clinicians to correct diagnosis in 4 cases and improved
the diagnosis of IIM subtypes in 4 cases. CONCLUSIONS: This study reflects the
interest of myositis dot in the rapid diagnosis process of patients with non
specific muscular symptoms leading to various diagnoses including IIM.
PMID- 27494324
TI - Prenatal Cocaine Exposure Upregulates BDNF-TrkB Signaling.
AB - Prenatal cocaine exposure causes profound changes in neurobehavior as well as
synaptic function and structure with compromised glutamatergic transmission.
Since synaptic health and glutamatergic activity are tightly regulated by brain
derived neurotrophic factor (BDNF) signaling through its cognate tyrosine
receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters
BDNF-TrkB signaling during brain development. Here we show prenatal cocaine
exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX)
of 21-day-old rats without affecting the expression levels of TrkB, P75NTR,
signaling molecules, NMDA receptor-NR1 subunit as well as proBDNF and BDNF.
Prenatal cocaine exposure reduces activity-dependent proBDNF and BDNF release and
elevates BDNF affinity for TrkB leading to increased tyrosine-phosphorylated
TrkB, heightened Phospholipase C-gamma1 and N-Shc/Shc recruitment and higher
downstream PI3K and ERK activation in response to ex vivo BDNF. The augmented
BDNF-TrkB signaling is accompanied by increases in association between activated
TrkB and NMDARs. These data suggest that cocaine exposure during gestation
upregulates BDNF-TrkB signaling and its interaction with NMDARs by increasing
BDNF affinity, perhaps in an attempt to restore the diminished excitatory
neurotransmission.
PMID- 27494329
TI - Why Do People Still Text While Driving?
PMID- 27494326
TI - Dopamine- and Tyrosine Hydroxylase-Immunoreactive Neurons in the Brain of the
American Cockroach, Periplaneta americana.
AB - The catecholamine dopamine plays several vital roles in the central nervous
system of many species, but its neural mechanisms remain elusive. Detailed
neuroanatomical characterization of dopamine neurons is a prerequisite for
elucidating dopamine's actions in the brain. In the present study, we
investigated the distribution of dopaminergic neurons in the brain of the
American cockroach, Periplaneta americana, using two antisera: 1) an antiserum
against dopamine, and 2) an antiserum against tyrosine hydroxylase (TH, an enzyme
required for dopamine synthesis), and identified about 250 putatively
dopaminergic neurons. The patterns of dopamine- and TH-immunoreactive neurons
were strikingly similar, suggesting that both antisera recognize the same sets of
"dopaminergic" neurons. The dopamine and TH antibodies intensively or moderately
immunolabeled prominent brain neuropils, e.g. the mushroom body (memory center),
antennal lobe (first-order olfactory center) and central complex (motor
coordination center). All subdivisions of the mushroom body exhibit both dopamine
and TH immunoreactivity. Comparison of immunolabeled neurons with those filled by
dye injection revealed that a group of immunolabeled neurons with cell bodies
near the calyx projects into a distal region of the vertical lobe, which is a
plausible site for olfactory memory formation in insects. In the antennal lobe,
ordinary glomeruli as well as macroglomeruli exhibit both dopamine and TH
immunoreactivity. It is noteworthy that the dopamine antiserum labeled tiny
granular structures inside the glomeruli whereas the TH antiserum labeled
processes in the marginal regions of the glomeruli, suggesting a different
origin. In the central complex, all subdivisions excluding part of the noduli and
protocerebral bridge exhibit both dopamine and TH immunoreactivity. These
anatomical findings will accelerate our understanding of dopaminergic systems,
specifically in neural circuits underlying aversive memory formation and arousal,
in insects.
PMID- 27494330
TI - Insta-Grams: The Effect of Consumer Weight on Reactions to Healthy Food Posts.
AB - Each day, social networking sites become increasingly inundated with food
imagery. Since many of these images are of fresh, vibrant, and healthy eats,
photo sharing of food through social media should have a long-term positive
effect on consumption habits. Yet, obesity rates in the United States continue to
rise, suggesting that people are spending more time posting images of healthy
foods and paying less attention to the actual foods they consume. This
confounding relationship could be explained by consumer weight, in that
overweight consumers desire to engage with social media maybe for the purpose of
expressing, presenting, and identifying with a healthy lifestyle. In the context
of food posts, individuals higher in body mass index may be more likely to engage
in social media activity (e.g., likes, shares, comments) that validates healthy
food choices to others in their online community. A between-subjects experimental
design tested this proposed effect using a manipulated Instagram post of a
healthy food item (i.e., black bean veggie burger). Results indicate that obese
individuals are more likely to engage with healthy food posts compared with their
normal weight and overweight counterparts. The effect is even more pronounced
when posts are absent of prior social media activity. Based upon these results,
obese individuals are encouraged to establish and maintain social network
connections with others who routinely post images of healthy food in their social
media feeds. Limitations and directions for future research are provided.
PMID- 27494328
TI - Cleavage of Model Substrates by Arabidopsis thaliana PRORP1 Reveals New Insights
into Its Substrate Requirements.
AB - Two broad classes of RNase P trim the 5' leader of precursor tRNAs (pre-tRNAs):
ribonucleoprotein (RNP)- and proteinaceous (PRORP)-variants. These two RNase P
types, which use different scaffolds for catalysis, reflect independent
evolutionary paths. While the catalytic RNA-based RNP form is present in all
three domains of life, the PRORP family is restricted to eukaryotes. To obtain
insights on substrate recognition by PRORPs, we examined the 5' processing
ability of recombinant Arabidopsis thaliana PRORP1 (AtPRORP1) using a panel of
pre-tRNASer variants and model hairpin-loop derivatives (pATSer type) that
consist of the acceptor-T-stem stack and the T-/D-loop. Our data indicate the
importance of the identity of N-1 (the residue immediately 5' to the cleavage
site) and the N-1:N+73 base pair for cleavage rate and site selection of pre
tRNASer and pATSer. The nucleobase preferences that we observed mirror the
frequency of occurrence in the complete suite of organellar pre-tRNAs in eight
algae/plants that we analyzed. The importance of the T-/D-loop in pre-tRNASer for
tight binding to AtPRORP1 is indicated by the 200-fold weaker binding of pATSer
compared to pre-tRNASer, while the essentiality of the T-loop for cleavage is
reflected by the near-complete loss of activity when a GAAA-tetraloop replaced
the T-loop in pATSer. Substituting the 2'-OH at N-1 with 2'-H also resulted in no
detectable cleavage, hinting at the possible role of this 2'-OH in coordinating
Mg2+ ions critical for catalysis. Collectively, our results indicate similarities
but also key differences in substrate recognition by the bacterial RNase P RNP
and AtPRORP1: while both forms exploit the acceptor-T-stem stack and the elbow
region in the pre-tRNA, the RNP form appears to require more recognition
determinants for cleavage-site selection.
PMID- 27494331
TI - Disclosure Pattern of Self-Labeled People Living with HIV/AIDS on Chinese Social
Networking Site: An Exploratory Study.
AB - HIV/AIDS is an important public health issue in China. The number of people
living with HIV/AIDS (PLWHA) has been increasing since the introduction of highly
active antiretroviral therapy. PLWHA's life quality is becoming an important
issue, with lack of research in China. In this study, a group of PLWHA (n = 663)
was identified using HIV/AIDS relevant usernames on a Chinese social networking
site (Weibo) to study their daily living situations. We found that more than
99.10% of PLWHA were male, among whom 90.80% turned out to be homosexual. They
had significantly more fans and followees, but fewer postings compared to the
general population. The mean age of the PLWHA was 28.96 (SD = 5.05) years old,
and southwest and northwest China had a high prevalence of HIV/AIDS. In addition,
PLWHA's postings were coded and we found that more than half of the postings (n =
769, 51.03%) contained strong emotions. Less than one-fifth of the postings were
directly related to HIV/AIDS topics (n = 269, 17.85%), while seeking emotional
support, such as looking for stable partnership, was ranked as the first priority
of support seeking. In summary, we found that the majority of the self-labeled
PLWHA were likely to be men who have sex with men. They used Weibo to share their
daily life events and seek emotional support. Implications for promoting HIV/AIDS
education and prevention through Chinese social networking sites were also
discussed.
PMID- 27494334
TI - Critical Factors Influencing Decision to Adopt Human Resource Information System
(HRIS) in Hospitals.
AB - The aim of this research is to explore factors influencing the management
decisions to adopt human resource information system (HRIS) in the hospital
industry of Bangladesh-an emerging developing country. To understand this issue,
this paper integrates two prominent adoption theories-Human-Organization
Technology fit (HOT-fit) model and Technology-Organization-Environment (TOE)
framework. Thirteen factors under four dimensions were investigated to explore
their influence on HRIS adoption decisions in hospitals. Employing non
probability sampling method, a total of 550 copies of structured questionnaires
were distributed among HR executives of 92 private hospitals in Bangladesh. Among
the respondents, usable questionnaires were 383 that suggesting a valid response
rate of 69.63%. We classify the sample into 3 core groups based on the HRIS
initial implementation, namely adopters, prospectors, and laggards. The obtained
results specify 5 most critical factors i.e. IT infrastructure, top management
support, IT capabilities of staff, perceived cost, and competitive pressure.
Moreover, the most significant dimension is technological dimension followed by
organisational, human, and environmental among the proposed 4 dimensions. Lastly,
the study found existence of significant differences in all factors across
different adopting groups. The study results also expose constructive proposals
to researchers, hospitals, and the government to enhance the likelihood of
adopting HRIS. The present study has important implications in understanding HRIS
implementation in developing countries.
PMID- 27494335
TI - Building a drug development database: challenges in reliable data availability.
AB - CONTEXT: Policy and legislative efforts to improve the biomedical innovation
process must rely on a detailed and thorough analysis of drug development and
industry output. OBJECTIVE: As part of our efforts to build a publicly-available
database on the characteristics of drug development, we present work undertaken
to test methods for compiling data from public sources. These initial steps are
designed to explore challenges in data extraction, completeness and reliability.
Specifically, filing dates for Investigational New Drugs (IND) applications with
the U.S. Food and Drug Administration (FDA) were chosen as the initial objective
data element to be collected. MATERIALS AND METHODS: FDA's Drugs@FDA database and
the Federal Register (FR) were used to collect IND dates for the 587 New
Molecular Entities (NMEs) approved between 1994 and 2014. When available, the
following data were captured: approval date, IND number, IND date and source of
information. RESULTS: At least one IND date was available for 445 (75.8%) of the
587 NMEs. The Drugs@FDA database provided IND dates for 303 (51.6%) NMEs and the
FR contributed with 297 (50.6%) IND dates. Out of the 445 NMEs for which an IND
date was obtained, 274 (61.6%) had more than one date reported. DISCUSSION: Key
finding of this paper is a considerable inconsistency in reliably available or
reported data elements, in this particular case, IND application filing dates as
assembled from publicly-available sources. CONCLUSION: Our team will continue to
focus on finding ways to collect relevant information to measure impact of drug
innovation.
PMID- 27494336
TI - The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized.
AB - BACKGROUND: Contaminated hospital surfaces are an important source of nosocomial
infections. A major obstacle in marketing antimicrobial surfaces is a lack of
efficacy data based on standardized testing protocols. AIM: We compared the
efficacy of multiple testing protocols against several "antimicrobial" film
surfaces. METHODS: Four clinical isolates were used: one Escherichia coli, one
Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry
methods (modified ISO 22196 and ASTM E2149), a "dried droplet", and a "transfer"
method were tested against two commercially available antimicrobial films, one
film in development, an untreated control, and a positive (silver) control film.
At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from
film surfaces and enumerated. RESULTS: Compared to untreated films in all
protocols, there were no significant differences in recovery on either commercial
brand at 2 or 24 hours after inoculation. The silver surface demonstrated
significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and
time points with the exception of 2 hours in the ISO protocol and the transfer
method. Using our novel droplet method, no differences between placebo and active
surfaces were detected. The surface in development demonstrated variable activity
depending on method, organism, and time point. The ISO demonstrated minimal
activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml
difference versus placebo). The ASTEM protocol exhibited significant differences
in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates
(10 fold decrease). Minimal activity was observed with this film in the transfer
method. CONCLUSIONS: Varying results between protocols suggested that efficacy of
antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use
should be considered and further development of representative methods is needed.
PMID- 27494337
TI - Do Your School Mates Influence How Long You Game? Evidence from the U.S.
AB - The goal of this paper is to estimate peer influence in video gaming time among
adolescents. Using a nationally representative sample of the U.S. school-aged
adolescents in 2009-2010, we estimate a structural model that accounts for the
potential biases in the estimate of the peer effect. Our peer group is
exogenously assigned and includes one year older adolescents in the same school
grade as the respondent. The peer measure is based on peers' own reports of video
gaming time. We find that an additional one hour of playing video games per week
by older grade-mates results in .47 hours increase in video gaming time by male
responders. We do not find significant peer effect among female responders.
Effective policies aimed at influencing the time that adolescents spend video
gaming should take these findings into account.
PMID- 27494338
TI - Chemical Approaches to Addressing the Instability and Toxicity of Lead-Halide
Perovskite Absorbers.
AB - The impressive rise in efficiencies of solar cells employing the three
dimensional (3D) lead-iodide perovskite absorbers APbI3 (A = monovalent cation)
has generated intense excitement. Although these perovskites have remarkable
properties as solar-cell absorbers, their potential commercialization now
requires a greater focus on the materials' inherent shortcomings and
environmental impact. This creates a challenge and an opportunity for synthetic
chemists to address these issues through the design of new materials. Synthetic
chemistry offers powerful tools for manipulating the magnificent flexibility of
the perovskite lattice to expand the number of functional analogues to APbI3. To
highlight improvements that should be targeted in new materials, here we discuss
the intrinsic instability and toxicity of 3D lead-halide perovskites. We consider
possible sources of these instabilities and propose methods to overcome them
through synthetic design. We also discuss new materials developed for realizing
the exceptional photophysical properties of lead-halide perovskites in more
environmentally benign materials. In this Forum Article, we provide a brief
overview of the field with a focus on our group's contributions to identifying
and addressing problems inherent to 3D lead-halide perovskites.
PMID- 27494339
TI - N-acetylcysteine with apocynin prevents hyperoxaluria-induced mitochondrial
protein perturbations in nephrolithiasis.
AB - Diminished mitochondrial activities were deemed to play an imperative role in
surged oxidative damage perceived in hyperoxaluric renal tissue. Proteomics is
particularly valuable to delineate the damaging effects of oxidative stress on
mitochondrial proteins. The present study was designed to apply large-scale
proteomics to describe systematically how mitochondrial proteins/pathways govern
the renal damage and calcium oxalate crystal adhesion in hyperoxaluria.
Furthermore, the potential beneficial effects of combinatorial therapy with N
acetylcysteine (NAC) and apocynin were studied to establish its credibility in
the modulation of hyperoxaluria-induced alterations in mitochondrial proteins. In
an experimental setup with male Wistar rats, five groups were designed for 9 d.
At the end of the experiment, 24-h urine was collected and rats were euthanized.
Urinary samples were analyzed for kidney injury marker and creatinine clearance.
Transmission electron microscopy revealed distorted renal mitochondria in
hyperoxaluria but combinatorial therapy restored the normal mitochondrial
architecture. Mitochondria were isolated from renal tissue of experimental rats,
and mitochondrial membrane potential was analyzed. The two-dimensional
electrophoresis (2-DE) based comparative proteomic analysis was performed on
proteins isolated from renal mitochondria. The results revealed eight
differentially expressed mitochondrial proteins in hyperoxaluric rats, which were
identified by Matrix-assisted laser desorption/ionization time of flight/time of
flight (MALDI-TOF/TOF) analysis. Identified proteins including those involved in
important mitochondrial processes, e.g. antioxidant defense, energy metabolism,
and electron transport chain. Therapeutic administration of NAC with apocynin
significantly expunged hyperoxaluria-induced discrepancy in the renal
mitochondrial proteins, bringing them closer to the controls. The results provide
insights to further understand the underlying mechanisms in the development of
hyperoxaluria-induced nephrolithiasis and the therapeutic relevance of the
combinatorial therapy.
PMID- 27494340
TI - Breast adenomyoepithelioma and adenomyoepithelioma with carcinoma (malignant
adenomyoepithelioma) with associated breast malignancies: A case series
emphasizing histologic, radiologic, and clinical correlation.
AB - The 2012 World Health Organization (WHO) classification of breast tumors
distinguishes adenomyoepitheliomas (AMEs) as benign tumors composed of a biphasic
proliferation of phenotypically variable myoepithelial cells around small
epithelial lined spaces. Many AMEs have demonstrated benign behavior and are
often cured with excision with negative margins, but some have exhibited
malignant transformation of the myoepithelial cells, ductal epithelial cells, or
both. When one of the components is histologically malignant, it is termed AME
with carcinoma. Due to the rarity, the literature correlating imaging, histology,
and clinical outcome is limited. A retrospective review was undertaken. A review
of an institutional pathology database identified 14 cases with AME or malignant
AME. Most AMEs had nonspecific imaging findings and were categorized as Bi-Rads
4. Histologic features of AME did not correlate with prior or concurrent breast
malignancies or any radiographic features. Clinical follow up could be obtained
for all but one case (mean follow up time = 75 months). 5 cases had no known
treatment post-biopsy and 5 patients received mastectomy. No recurrences were
noted. 3/13 cases of benign AME had associated breast malignancies including
invasive ductal adenocarcinoma and ductal carcinoma in-situ. 1 case of malignant
AME had a synchronous separate malignant phyllodes tumor. Given the unclear and
unpredictable propensity for malignant transformation, conservative excision with
negative margins currently seems appropriate.
PMID- 27494341
TI - The impact of angry rumination on anger-primed cognitive control.
AB - BACKGROUND AND OBJECTIVES: Recent research suggests that angry rumination
augments aggressive behavior by depleting self-control resources. Yet, few
studies have been conducted to empirically support this proposal. In the present
study, we therefore sought to investigate the effects of angry rumination,
relative to distraction, on self-reported anger and a behavioral indicator of
self-control. METHODS: Seventy-two participants recalled and imagined an anger
inducing autobiographical memory and were instructed to engage in either angry
rumination (n = 37) or distraction (n = 35). Following these emotion regulation
instructions, participants performed an affective Go/NoGo task in order to assess
behavioral self-control along with several questionnaires to assess anger related
constructs. RESULTS: As expected, results revealed that angry rumination
augmented anger, whereas anger decreased in the distraction condition. Contrary
to predictions, we found no differences between both groups in performance on the
affective Go/NoGo task. LIMITATIONS: A potential limitation is we instructed our
participants on how to regulate their emotions rather than letting angry
rumination occur spontaneously. CONCLUSIONS: The findings indicate that whereas
angry rumination results in heightened anger, it does not seem to result in lower
self-control as measured with a behavioral task that requires cognitive control.
More research is needed to test the boundary conditions regarding the role of
self-control in understanding rumination-induced aggression.
PMID- 27494342
TI - Upright posture improves affect and fatigue in people with depressive symptoms.
AB - BACKGROUND AND OBJECTIVES: Slumped posture is a diagnostic feature of depression.
While research shows upright posture improves self-esteem and mood in healthy
samples, little research has investigated this in depressed samples. This study
aimed to investigate whether changing posture could reduce negative affect and
fatigue in people with mild to moderate depression undergoing a stressful task.
METHODS: Sixty-one community participants who screened positive for mild to
moderate depression were recruited into a study purportedly on the effects of
physiotherapy tape on cognitive function. They were randomized to sit with usual
posture or upright posture and physiotherapy tape was applied. Participants
completed the Trier Social Stress Test speech task. Changes in affect and fatigue
were assessed. The words spoken by the participants during their speeches were
analysed. RESULTS: At baseline, all participants had significantly more slumped
posture than normative data. The postural manipulation significantly improved
posture and increased high arousal positive affect and fatigue compared to usual
posture. The upright group spoke significantly more words than the usual posture
group, used fewer first person singular personal pronouns, but more sadness
words. Upright shoulder angle was associated with lower negative affect and lower
anxiety across both groups. LIMITATIONS: The experiment was only brief and a non
clinical sample was used. CONCLUSIONS: This preliminary study suggests that
adopting an upright posture may increase positive affect, reduce fatigue, and
decrease self-focus in people with mild-to-moderate depression. Future research
should investigate postural manipulations over a longer time period and in
samples with clinically diagnosed depression.
PMID- 27494344
TI - Role of miR-146a in the Regulation of Inflammation in an In Vitro Model of
Graves' Orbitopathy.
AB - PURPOSE: To investigate the role of microRNA 146a (miR-146a) in the regulation of
inflammation in an in vitro model of Graves' orbitopathy (GO). METHODS: The level
of miR-146a expression in orbital adipose tissue was compared between GO and non
GO by quantitative real-time PCR (qPCR). The effects of interleukin 1beta (IL
1beta) on miR-146a expression were analyzed in orbital fibroblasts by qPCR. To
investigate the molecular mechanism underlying IL-1beta-induced miR-146a
expression, the effects of inhibitors of nuclear factor kappa-light-chain
enhancer of activated B cells (NF-kappaB), mitogen-activated protein
kinase/extracellular signal-regulated kinases (MEK)-1/2, c-Jun N-terminal kinases
(JNK)-1/2, p38 MAP kinase, and phosphatidylinositol-4,5-bisphosphate 3-kinase
(PI3K) were analyzed. The effects of miR-146a mimics and inhibitors on IL-1beta
induced IL-6 release were examined by ELISA and Western blotting. RESULTS: The
level of miR-146a expression was significantly higher in GO orbital adipose
tissue than in non-GO (P = 0.032). Interleukin 1beta induced a time- and
concentration-dependent increase in miR-146a expression. Interleukin 1beta (10
ng/mL, 16 hours) induced an approximately 17.5-fold increase in miR-146
expression. The increase in miR-146a expression by IL-1beta was significantly
inhibited by NF-kappaB, JNK-1/2, and PI3K inhibitors (1.94 +/- 0.25, 5.28 +/-
0.34 and 9.73 +/- 2.32-fold, respectively, P < 0.05 compared with IL-1beta
induced miR-146 expression, independent t-test). Interleukin 1beta-induced IL-6
protein production was further decreased by miR-146a mimics, but not by
inhibitors of miR-146a. CONCLUSIONS: MicroRNA 146a was upregulated by
inflammatory stress in orbital fibroblasts. Our results indicated that miR-146a
had a positive effect on the anti-inflammatory process. MicroRNA 146a may play a
role in the regulation of inflammation in orbital fibroblasts, and may
participate in the pathogenesis of GO.
PMID- 27494343
TI - CNTF Attenuates Vasoproliferative Changes Through Upregulation of SOCS3 in a
Mouse-Model of Oxygen-Induced Retinopathy.
AB - PURPOSE: Retinal vascular disease represents a major cause for vision loss in the
Western world. Recent research has shown that neuronal and vascular damage are
closely related in retinal disease. Ciliary neurotrophic factor (CNTF) is a well
studied neurotrophic factor that is currently being tested in clinical trials for
the treatment of retinal degenerative diseases and macular telangiectasia.
However, little is known about its effect on retinal vasculature. In this study,
we investigate the effects of CNTF in retinal neovascular disease using the mouse
model of oxygen-induced retinopathy (OIR). METHODS: Newborn pups were exposed to
75% oxygen from postnatal day (P)7 to P12 and subsequently returned to room air.
Ciliary neurotrophic factor was injected intravitreally at OIR P12 and the vaso
obliterated and neovascular areas were quantified at OIR P17.
Immunohistochemistry, RNA, and protein analysis were used to identify CNTF
responsive cells. In vitro experiments were performed to analyze the effect of
CNTF on endothelial and astroglial cells. RESULTS: In the OIR model, CNTF
facilitated capillary regrowth and attenuated preretinal neovascularization in a
dose-dependent manner. The protective effect of CNTF was mediated via activation
of the JAK/STAT3/SOCS3 signaling pathway. Immunohistochemical studies identified
endothelial cells among others as CNTF-responsive cells in the retina. In vitro
studies confirmed the anti-angiogenic effect of CNTF on endothelial cell
sprouting. CONCLUSIONS: This study provides evidence for a therapeutic potential
of CNTF beyond degenerative retinal disease. Vasoproliferative retinopathies may
benefit from a CNTF-dependent and SOCS3-mediated angiomodulatory effect.
PMID- 27494345
TI - Peripheral Blood Mitochondrial DNA Damage as a Potential Noninvasive Biomarker of
Diabetic Retinopathy.
AB - PURPOSE: In the development of diabetic retinopathy, retinal mitochondria become
dysfunctional, and mitochondrial DNA (mtDNA) is damaged. Because retinopathy is a
progressive disease, and circulating glucose levels are high in diabetes, our aim
was to investigate if peripheral blood mtDNA damage can serve as a potential
biomarker of diabetic retinopathy. METHODS: Peripheral blood mtDNA damage was
investigated by extended-length PCR in rats and mice, diabetic for 10 to 12
months (streptozotocin-induced, type 1 model), and in 12- and 40-week-old Zucker
diabetic fatty rats (ZDF, type 2). Mitochondrial copy number (in gDNA) and
transcription (in cDNA) were quantified by qPCR. Similar parameters were measured
in blood from diabetic patients with/without retinopathy. RESULTS: Peripheral
blood from diabetic rodents had significantly increased mtDNA damage and
decreased copy numbers and transcription. Lipoic acid administration in diabetic
rats, or Sod2 overexpression or MMP-9 knockdown in mice, the therapies that
prevent diabetic retinopathy, also ameliorated blood mtDNA damage and restored
copy numbers and transcription. Although blood from 40-week-old ZDF rats had
significant mtDNA damage, 12-week-old rats had normal mtDNA. Diabetic patients
with retinopathy had increased blood mtDNA damage, and decreased transcription
and copy numbers compared with diabetic patients without retinopathy and
nondiabetic individuals. CONCLUSIONS: Type 1 diabetic rodents with oxidative
stress modulated by pharmacologic/genetic means, and type 2 animal model and
patients with/without diabetic retinopathy, demonstrate a strong relation between
peripheral blood mtDNA damage and diabetic retinopathy, and suggest the
possibility of use of peripheral blood mtDNA as a noninvasive biomarker of
diabetic retinopathy.
PMID- 27494346
TI - Perceived Visual Distortions in Juvenile Amblyopes During/Following Routine
Amblyopia Treatment.
AB - PURPOSE: To establish the point prevalence of perceived visual distortions (PVDs)
in amblyopic children; the association between severity of PVDs and clinical
parameters of amblyopia; and the relationship between PVDs and amblyopia
treatment outcomes. METHODS: Perceived visual distortions were measured using a
16-point dichoptic alignment paradigm in 148 visually normal children (aged, 9.18
+/- 2.51 years), and 82 amblyopic children (aged, 6.33 +/- 1.48 years) receiving
or following amblyopia treatment. Global distortion (GD; vector sum of mean
centered individual alignment error between physical and perceived target
location) and Global uncertainty (GU; SD of GD over two experiment runs) were
compared to age-matched control data, and correlated against clinical parameters
of amblyopia (type, monocular visual acuity, pretreatment interocular acuity
difference, refractive error, age at diagnosis, motor fusion, stereopsis, near
angle of deviation) and amblyopia treatment outcomes (refractive adaption
duration, treatment duration, occlusion dosage, posttreatment interocular acuity
difference, number of lines improvement). RESULTS: Point prevalence of PVDs in
amblyopes was 56.1%. Strabismic amblyopes experienced more severe distortions
than anisometropic or microtropic amblyopes (GD Kruskal Wallis H = 16.89, P <
0.001; GU Kruskal Wallis H = 15.31, P < 0.001). Perceived visual distortions
severity moderately correlated with the strength of binocular function, (e.g.,
log stereoacuity [GD rho = 0.419, P < 0.001; GU rho = 0.384, P < 0.001)], and
strongly with near angle of deviation (GD rho = 0.578, P < 0.001; GU rho = 0.384,
P < 0.001). There was no relationship between severity of PVDs and amblyopia
treatment outcomes, or the amblyopic visual acuity deficit. Perceived visual
distortions persisted in more than one-half of treated amblyopic cases whose
treatment was deemed successful. CONCLUSIONS: Perceived visual distortions are
common symptoms of amblyopia and are correlated with binocular (stereoacuity,
angle of deviation), but not monocular (visual acuity) clinical outcomes. This
adds to evidence demonstrating the role of decorrelated binocular single vision
in many aspects of amblyopia, and emphasizes the importance of restoring and
improving binocular single vision in amblyopic individuals.
PMID- 27494347
TI - Therapeutic Effect of Protocatechuic Aldehyde in an In Vitro Model of Graves'
Orbitopathy.
AB - PURPOSE: Protocatechuic aldehyde (3,4-dihydroxybenzaldehyde; PCA) is extracted
from Salvia miltiorrhiza, and has been reported to possess antiproliferative,
antioxidant, and antiadipogenesis properties in various in vivo and in vitro
experiments. This study aimed to outline the antioxidant and suppressive effects
of PCA on adipogenesis and hyaluronan production in orbital fibroblasts to help
with designing therapeutic approaches for Graves' orbitopathy (GO). METHODS: We
assessed the in vitro effects of PCA on orbital fibroblasts, which were cultured
from orbital fat tissue obtained from patients undergoing orbital decompression
for severe GO. Control tissue was obtained from patients undergoing orbital
surgery with no history of GO or Graves' hyperthyroidism. RESULTS: The 2,2
diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic
acid) diammonium salt assay results confirmed the free radical scavenging effect
of PCA after treatment. Protocatechuic aldehyde exhibited a suppressive effect on
intracellular reactive oxygen species generation and upregulated heme oxygenase-1
expression in Western blot analysis. Protocatechuic aldehyde attenuated TNF-alpha
and IL-1beta-induced hyaluronan production. Oil Red-O staining results revealed a
decrease in lipid droplets and suppressed expression of the adipogenesis-related
proteins peroxisome proliferator-activated receptor (PPAR)-gamma, CCAAT/enhancer
binding protein (c/EBP)-alpha, and c/EBP-beta upon treatment with PCA during
adipose differentiation. CONCLUSIONS: In this study, PCA exerted significant
antioxidant and antiadipogenic effects and inhibited the production of hyaluronan
in GO orbital fibroblasts. Accordingly, PCA potentially could be used as a novel
treatment option for GO.
PMID- 27494348
TI - A new CE with contactless conductivity detection method for the determination of
complex cationic compositions: Application to the analysis of pen inks.
AB - A CE with contactless conductivity detection methodology using a novel background
electrolyte for the separation and determination of 17 metal cations (Cs+ , Rb+ ,
K+ , Ca2+ , Na+ , Mg2+ , Mn2+ , Sr2+ , Li+ , Ba2+ , Fe2+ , Pb2+ , Cd2+ , Zn2+ ,
Co2+ , Cu2+ and Ni2+ ) and ammonium has been investigated. The buffer, based on
lactic acid and beta-alanine, was experimentally compared with other two commonly
used electrolytes, showing important improvements, such as shorter analysis times
(<11 min), better electrophoretic resolutions and higher detectabilities for
certain analytes, such as Fe2+ and Pb2+ . The inclusion of other additives such
as 18-Crown-6 and alpha-hydroxyisobutyric acid was studied in order to obtain the
best separation of the analytes of interest. The optimised method was applied to
the analysis of 11 water-based pen inks and the determination of their metal
composition. The methodology was demonstrated for the comparison and
differentiation of pen inks.
PMID- 27494349
TI - The Different Roles of Entropy and Solubility in High Entropy Alloy Stability.
AB - Multiprincipal element high entropy alloys stabilized as a single alloy phase
represent a new material system with promising properties, such as high corrosion
and creep resistance, sluggish diffusion, and high temperature tensile strength.
However, the mechanism of stabilization to form single phase alloys is
controversial. Early studies hypothesized that a large entropy of mixing was
responsible for stabilizing the single phase; more recent work has proposed that
the single-phase solid solution is the result of mutual solubility of the
principal elements. Here, we demonstrate the first self-consistent study of the
relative importance of these two proposed mechanisms. In situ high-throughput
synchrotron diffraction studies were used to monitor the stability of the single
phase alloy in thin-film (Al1-x-yCuxMoy)FeNiTiVZr composition spread samples. Our
results indicate that a metastable solid solution can be captured via the rapid
quenching typical of physical vapor deposition processes, but upon annealing the
solid-solution phase stability is primarily governed by mutual miscibility.
PMID- 27494350
TI - The Impact of Gestational Age at Delivery on Urologic Outcomes for the Fetus with
Hydronephrosis.
AB - OBJECTIVE: Compare short-term urologic outcomes with delivery timing in fetuses
with severe hydronephrosis. METHODS: An ultrasound database was queried for
severe hydronephrosis. Cases were categorized into late preterm/early term (36
0/7 - 38 6/7 weeks) and full term (39 0/7 weeks or greater) groups. Baseline
characteristics were compared using standard statistical methods. Spearman's
correlation analysis was performed for grade and severity of hydronephrosis on
first postnatal ultrasound with gestational age at delivery. RESULTS: Of 589
cases, 79 (33 late preterm/early term, 46 full term) met criteria. Baseline
characteristics were similar between groups. Spearman's correlation coefficients
(rs) indicated that increased postnatal Society for Fetal Urology grade, rs=
0.26 (95% CI [-.48, -.002]), and severity of hydronephrosis, rs= -0.39 (95% CI [
.59, -.14]), both correlated with earlier delivery. CONCLUSION: Late
preterm/early term delivery resulted in worse short-term postnatal renal
outcomes. Unless otherwise indicated, delivery for fetal hydronephrosis should be
deferred until 39 weeks.
PMID- 27494351
TI - Insights into the Effects of Zinc Doping on Structural Phase Transition of P2
Type Sodium Nickel Manganese Oxide Cathodes for High-Energy Sodium Ion Batteries.
AB - P2-type sodium nickel manganese oxide-based cathode materials with higher energy
densities are prime candidates for applications in rechargeable sodium ion
batteries. A systematic study combining in situ high energy X-ray diffraction
(HEXRD), ex situ X-ray absorption fine spectroscopy (XAFS), transmission electron
microscopy (TEM), and solid-state nuclear magnetic resonance (SS-NMR) techniques
was carried out to gain a deep insight into the structural evolution of P2
Na0.66Ni0.33-xZnxMn0.67O2 (x = 0, 0.07) during cycling. In situ HEXRD and ex situ
TEM measurements indicate that an irreversible phase transition occurs upon
sodium insertion-extraction of Na0.66Ni0.33Mn0.67O2. Zinc doping of this system
results in a high structural reversibility. XAFS measurements indicate that both
materials are almost completely dependent on the Ni(4+)/Ni(3+)/Ni(2+) redox
couple to provide charge/discharge capacity. SS-NMR measurements indicate that
both reversible and irreversible migration of transition metal ions into the
sodium layer occurs in the material at the fully charged state. The irreversible
migration of transition metal ions triggers a structural distortion, leading to
the observed capacity and voltage fading. Our results allow a new understanding
of the importance of improving the stability of transition metal layers.
PMID- 27494352
TI - Photoelectrochromism in the Retinal Protonated Schiff Base Chromophore:
Photoisomerization Speed and Selectivity under a Homogeneous Electric Field at
Different Operational Regimes.
AB - The spectral tunability, photoisomerization efficiency and selectivity, of the
native all-trans retinal protonated Shiff base (PSB) chromophore driven by a
homogeneous electric field is systematically investigated. By analyzing the
absorption wavelength dependence, charge distribution, and PES profiles along
selected torsional angles, as well as the electronic structure, energetics, and
topography of the CI seam in the presence of strong positive and negative
electric fields, we recognize the existence of qualitatively/fundamentally
different photophysics and photochemistry with respect to the unperturbed (i.e.,
absence of an electric field) chromophore. We rationalize the findings within the
scope of molecular orbital theory and deliver a unified picture of the
photophysics of the retinal PSB chromophore over a wide, even beyond the usually
observed, spectral regime, ranging from the near-infrared to the ultraviolet
absorption energies. This work has a 3-fold impact: a) it accounts for, and
extends, previous theoretical studies on the subject; b) it delivers a rationale
for the ES lifetimes observed in retinal proteins, both archeal and visual
rhodopsins, as well as in solvent; and c) the transferability of the discovered
trends on PSB mimics is demonstrated.
PMID- 27494353
TI - Revisiting the Male-Produced Aggregation Pheromone of the Lesser Mealworm,
Alphitobius diaperinus (Coleoptera, Tenebrionidae): Identification of a Six
Component Pheromone from a Brazilian Population.
AB - The lesser mealworm, Alphitobius diaperinus Panzer 1797 (Coleoptera:
Tenebrionidae), is a cosmopolitan insect pest affecting poultry production. Due
to its cryptic behavior, insecticide control is usually not efficient. Thus,
sustainable and effective methods would have an enormous and positive impact in
poultry production. The aim of this study was to confirm the identity of the male
produced aggregation pheromone for a Brazilian population of A. diaperinus and to
evaluate its biological activity in behavioral assays. Six male-specific
compounds were identified: (R)-limonene (1), (E)-ocimene (2), 2-nonanone (3), (S)
linalool (4), (R)-daucene (5), all described before in an American population,
and a sixth component, (E,E)-alpha-farnesene (6), which is apparently exclusive
to a Brazilian population. Y-Tube bioassays confirmed the presence of a male
produced aggregation pheromone and showed that all components need to be present
in a similar ratio and concentration as emitted by male A. diaperinus to produce
a positive chemotactic response.
PMID- 27494354
TI - Risks and benefits of epilepsy surgery in a pediatric population: Consequences
for memory and academic skills.
AB - We examined benefits and risks for memory and academic functioning associated
with epilepsy surgery in a pediatric population. A total of 46 patients with
intractable seizures and a single seizure focus were divided into four groups
according to focus localization: right temporal, left temporal, frontal, and
parietal/occipital region. Pre- and postsurgery performance measures were
compared across groups and with a fifth group of patients that had intractable
seizures but did not undergo surgery. Both groups with temporal lobe epilepsy
showed significant declines in memory test scores, while performance of the group
with frontal lobe epilepsy improved. These changes were mirrored in parental
reports of everyday memory. Consistent with other pediatric studies, no
lateralized material-specific declines in the groups with temporal lobe epilepsy
were found. When memory improved, the improvement was associated with decreases
in seizure frequency and the number of anticonvulsant medications. Presurgical
performance was the best predictor of declines in memory test performance.
Deterioration of academic test scores in the group that did not have surgery
exemplified a potential risk of living with seizures and antiepilepsy medication.
PMID- 27494355
TI - Interictal epileptic discharge correlates with global and frontal cognitive
dysfunction in temporal lobe epilepsy.
AB - OBJECTIVE: Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread
effects on structural and functional connectivity and often entails cognitive
dysfunction. EEG is mandatory to disentangle interactions in epileptic and
physiological networks which underlie these cognitive comorbidities. Here, we
examined how interictal epileptic discharges (IEDs) affect cognitive performance.
METHODS: Thirty-four patients (right TLE=17, left TLE=17) were examined with 24
hour video-EEG and a battery of neuropsychological tests to measure intelligence
quotient and separate frontal and temporal lobe functions. Hippocampal
segmentation of high-resolution T1-weighted imaging was performed with
FreeSurfer. Partial correlations were used to compare the number and distribution
of clinical interictal spikes and sharp waves with data from imagery and
psychological tests. RESULTS: The number of IEDs was negatively correlated with
executive functions, including verbal fluency and intelligence quotient (IQ).
Interictal epileptic discharge affected cognitive function in patients with left
and right TLE differentially, with verbal fluency strongly related to
temporofrontal spiking. In contrast, IEDs had no clear effects on memory
functions after corrections with partial correlations for age, age at disease
onset, disease duration, and hippocampal volume. CONCLUSION: In patients with TLE
of long duration, IED occurrence was strongly related to cognitive deficits, most
pronounced for frontal lobe function. These data suggest that IEDs reflect
dysfunctional brain circuitry and may serve as an independent biomarker for
cognitive comorbidity.
PMID- 27494356
TI - Electroclinical aspects and therapy of Han patients with juvenile myoclonic
epilepsy in northern China.
AB - OBJECTIVE: The objective of this study was to assess the electroclinical aspects
and treatment of Han patients with juvenile myoclonic epilepsy (JME) in northern
China. METHODS: One hundred fifty-six outpatients with JME from six epilepsy
centers, between January 2011 and June 2012, were followed up for at least two
years. They underwent twenty-four-hour video-EEG recording. Brain imaging was
performed using magnetic resonance imaging (MRI). Clinical aspects,
electroencephalographic (EEG) features, and antiepileptic drugs (AEDs) received
were reviewed. RESULTS: Generalized tonic-clonic seizures (GTCS) were found in
150/156 patients. Delay of diagnosis was 4.60+/-9.92years. Photosensitivity was
more common in eye closure condition during IPS in patients with JME; in
addition, patients with JME with myoclonic seizures (MS) and GTCS as seizure
types were likely to present photoparoxysmal responses (PPRs). The 82 nontreated
patients showed a median latency to first interictal or ictal generalized spike
wave discharge (GSWD) of 50min (IQR: 22-102min). The first GSWDs were recorded in
63%, 76%, 90%, and 98% patients within one, two, three, and 4h, respectively;
only 2% of patients had first GSWDs after 4h. One hundred eleven patients
(111/156) chose extended-release valproate (VPA) at daily doses <=1000mg. The
percentages of seizure-free patients among MS, GTCS, and absence seizure (AS)
groups were 88.3%, 99.0%, and 94.9%, respectively. CONCLUSION: Photoparoxysmal
responses were more common in patients with JME with MS and GTCS and rare in
patients with JME with MS and AS in northern Chinese Han patients. Most patients
with JME in northern China chose VPA as first therapeutic choice, and low dose
(500 to 1000mg daily) of extended-release VPA may be an optimal choice for them.
Video-EEG monitoring for at least 4h may be helpful in detecting the first
interictal or ictal GSWD in patients with potential JME. Moreover, video-EEG
monitoring performed at about 9 o'clock in the morning with patients in the awake
state might be useful to find the first GSWD. For JME diagnosis, Class II
criteria are more helpful than Class I counterparts, the latter yielding more
missed diagnoses.
PMID- 27494357
TI - Vocational factors which predict seizure prognosis in young adults during
military service.
AB - BACKGROUND: The vocational parameters regarding epilepsy are not well
established. Our aim was to assess the risk of seizures as a function of
occupational stress and disease severity in military recruits of the IDF (Israel
Defense Force) and to examine the effect of new classification criteria (used
between the late nineties and early two thousands) in comparison with that of
previous criteria (used during the mid-eighties to mid-nineties). METHODS: The
medical records of over 150,000 18-year-old men recruited to the IDF between the
mid-nineties and the mid-two thousands were used to assemble a cohort, which was
followed for a period of 36months. The severity of the disease was determined
according to 3 categories, according to the medical history. The recruits were
subdivided according to their occupational categories to Combat Units (CUs),
Maintenance Units (MUs), and Administrative Units (AUs). We compared the
incidence rates of the different groups with the findings from a previous follow
up. RESULTS: The annual incidence rates during 36months of follow-up were 0.026%,
4.7%, and 8.8%, in categories 1 to 3, respectively. The relative risk of seizure
incidence in CU and MU was lower than in AU (0.42 and 0.81, p<0.0001). Similar
findings were found in other disease categories. CONCLUSIONS: Job assignment to
CU (less convenient conditions like sleep deprivation and strenuous physical
activity) did not increase the incidence of seizures. It was found that EEG
examination is an important criterion in the vocational evaluation of subjects
that have had one or more seizures. This study supports the establishment of
vocational criteria and recommends the integration of people diagnosed with
epilepsy in most occupations.
PMID- 27494358
TI - Epilepsy or seizure disorder? The effect of cultural and socioeconomic factors on
self-reported prevalence.
AB - Self-reported epilepsy may be influenced by culture, knowledge, and beliefs. We
screened 6420 residents of the District of Columbia (DC) for epilepsy to
investigate whether socio-demographics were associated with whether they reported
their diagnosis as epilepsy or as seizure disorder. Lifetime and active
prevalence rates were 0.54% and 0.21%, respectively for 'epilepsy' and 1.30% and
0.70%, respectively for 'seizure disorder'. Seizure disorder was reported
significantly more often than epilepsy among blacks, females,
respondents>=50years, those with lower level education, respondents who lived
alone and in low income neighborhoods, and those who resided in DC for at least
five years. Clinicians should assure that patients and caregivers understand that
epilepsy is synonymous with seizure disorder and other culturally appropriate
terms, in order to optimize compliance with treatment, disease management
instructions, and utilization of other resources targeted at persons with
epilepsy. Furthermore, education and awareness campaigns aimed at improving
access-to-care, reducing stigma, and increasing awareness of adverse events, such
as SUDEP, should include a more diverse definition of epilepsy in their messages.
PMID- 27494359
TI - Local brain activity persists during apparently generalized postictal EEG
suppression.
AB - OBJECTIVES: Postictal generalized EEG suppression (PGES) frequently occurs after
generalized convulsive seizures (GCS) and may be involved in the pathophysiology
of sudden unexpected death in epilepsy (SUDEP). It is usually determined using
conventional scalp EEG which is likely to miss cerebral activity in deeper brain
structures. Here, we examined intracranial EEG activity after GCS to unravel the
pattern and extent of local brain activity during apparent PGES on scalp EEG (s
PGES). METHODS: We retrospectively reviewed electroencephalographic data of
people with chronic epilepsy who had GCS during presurgical video-EEG monitoring
using simultaneous intracranial and scalp EEG (10-20 system) electrodes. RESULTS:
Twenty-five GCS (20 with s-PGES) of 15 patients with an average number of 88+/-42
intracranial electrode contacts were included. The majority of GCS with s-PGES
(18 of 20) displayed persisting or reemerging intracranial EEG activity during
apparent PGES on scalp EEG. Three patterns were identified: Pattern 1 (11 GCS, 6
patients) consisted of continuous local interictal activity; Pattern 2 (5 GCS, 5
patients) displayed suppressed EEG activity at all intracranial contacts in the
early phase of s-PGES, but reemerging local brain activity before s-PGES
dissolved; and Pattern 3 (2 GCS, 2 patients) showed persistent local ictal
activity during s-PGES. Persisting intracranial EEG activity at PGES onset on
scalp EEG was present in 10+/-14% (range: 0 to 42%) of all intracranial contacts
and mostly in the temporal lobe. CONCLUSIONS: Our results reveal that, during
apparently generalized postictal EEG suppression, local brain activity persists
or reemerges in most GCS. Possible implications of this localized neuronal
activity in the context of SUDEP are discussed in the paper.
PMID- 27494360
TI - Conversation analysis in the differentiation of psychogenic nonepileptic and
epileptic seizures in pediatric and adolescent settings.
AB - The differential diagnosis of epileptic seizures (ES) and psychogenic
nonepileptic seizures (PNES) is often difficult, especially in pediatric and
adolescent settings. Conversation analysis (CA) can be a worthwhile diagnostic
tool in adults. The aim of this study was to assess the diagnostic value of CA in
Italian children and adolescents. Ten patients (seven females and three males),
diagnosed using video-EEG as having either ES or PNES, underwent a video-recorded
interview by a physician from outside the center specifically trained for this
purpose. An external linguistic rater then examined the video recordings and
transcripts using CA. Diagnoses formulated on the basis of interactional and
linguistic features of the patients' speech were compared with diagnoses made by
seizure experts on the basis of all available clinical information including the
video-EEG findings. Conversation analysis diagnoses corresponded to the video-EEG
diagnoses in 8 out of 10 cases. In conclusion, while some conversational
adaptation is necessary to enable children and adolescents to share their seizure
experiences with an adult health professional, this study indicates the
differential diagnostic potential of a CA approach in these young people with
PNES or epilepsy. Larger samples are obviously needed to confirm these findings.
PMID- 27494361
TI - Biological diversity of Salix taxa in Cu, Pb and Zn phytoextraction from soil.
AB - The aim of the study was to estimate the efficiency of copper (Cu), lead (Pb) and
zinc (Zn) phytoextraction by 145 Salix taxa cultivated in an area affected by
industrial activity. Survivability and biomass of plants were also analyzed. The
highest Cu, Pb and Zn content in shoots was 33.38 +/- 2.91 (S. purpurea *
viminalis 8), 24.64 +/- 1.97 (S. fragilis 1) and 58.99 +/- 4.30 (S. eriocephala
7) mg kg-1 dry weight, respectively. In the case of unwashed leaves, the highest
content of these metals was 135.06 +/- 8.14 (S. purpurea 26), 67.98 +/- 5.27 (S.
purpurea 45) and 142.56 +/- 12.69 (S. alba * triandra 2) mg kg-1 dw, while in
washed leaves it was 106.02 +/- 11.12 (S. purpurea 45), 55.06 +/- 5.75 (S.
purpurea 45) and 122.87 +/- 12.33 (S. alba * triandra 2) mg kg-1 dw,
respectively. The differences between the highest and lowest values for Cu, Pb
and Zn were 545%, 20500% and 535% in shoots; 2692%, 2560% and 7500% in unwashed
leaves; and 3286%, 2221% and 6950% in washed leaves, respectively. S. acutifolia
was able to effectively accumulate all three metals jointly, producing shoots
that were well developed in both length and diameter when compared with the other
tested willows-an ability that would suggest its high suitability for practical
application.
PMID- 27494362
TI - Where is the future of cardiac lead extraction heading?
AB - INTRODUCTION: Transvenous lead extraction (TLE) is the gold standard for lead
removal. The increasing rate of cardiac implantable electronic device (CIED)
implantations and of CIED related complications highlight the importance of
transvenous lead extraction . AREAS COVERED: The TLE scenario is constantly
changing. Optimizing lead related technology and improving TLE practice across
the world are the cornerstones to improving safety and efficacy. We review the
state of the art in TLE, focusing on potential future implications and
improvements in terms of skills and technologies. Expert commentary: The
increased number of extractions will increase the necessity of safe and effective
TLE. New technologies, techniques and appropriate training is warranted across
the world.
PMID- 27494363
TI - Formation of Ordered Phospholipid Monolayer on a Hydrophilically Modified Au(111)
Substrate.
AB - The molecular arrangement of phospholipid molecules was investigated on a
hydrophilically modified gold surface within an aqueous solution by scanning
tunneling microscopy. By suspending phospholipid (1-palmitoyl-2-oleoyl-sn-glycero
3-phosphocholine, POPC) nanoparticles in the aqueous electrolyte surrounding a
hydrophilically modified gold (111) substrate with 3-mercaptopropionic acid (SH
C2H4-COOH, 3-MPA), well-ordered adlattices of POPC were observed. Traces of
particle fusion were visualized before formation of the adlattice. Addition of
cholesterol to the suspension seems to facilitate accommodation of POPC on this
surface. The observed unit cells of POPC adlattices had dimensions of 0.5 nm *
1.9-2.5 nm. By high-resolution imaging, each unit cell was discerned to be
occupied by one upright POPC molecule. The POPC + cholesterol suspension also
leads to formation of a flat integrated POPC layer, which may be a lipid bilayer
covering the surface.
PMID- 27494365
TI - PdCuPt Nanocrystals with Multibranches for Enzyme-Free Glucose Detection.
AB - By carefully controlling the synthesis condition, branched PtCu bimetallic
templates were synthesized in aqueous solution. After the galvanic replacement
reaction between PtCu templates and the Pt precursors, PdCuPt trimetallic
nanocrystals with branched structures were obtained. Owing to the open structure
and the optimized composition, the electrochemical experimental results reveal
that the PdCuPt trimetallic nanocrystals possess high electrocatalytic activity,
selectivity and stability for the oxidation of glucose in alkaline solution. In
detail, a detection limit of 1.29 MUM and a sensitivity of 378 MUA/mM/cm(2) are
achieved. The good electrocatalytic performance should be attributed to the
unique branched nanostructure as well as the synergistic effect among metals. The
superior catalytic properties suggest that these nanocrystals are promising for
enzyme-free detection of glucose.
PMID- 27494366
TI - The potential of cystatin-C to evaluate the prognosis of acute heart failure: A
comparative study.
AB - BACKGROUND: The prognosis of acute heart failure (HF) can be determined by cardio
renal function which is assessed by cystatin-C (Cys-C). We evaluated whether Cys
C could be a more useful prognostic indicator in acute HF, compared with uric
acid (UA) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS: Two
hundred thirty-two HF patients in the emergency room were studied using
measurements of Cys-C, UA, and NT-proBNP. During the follow-up, cardiac events,
defined as the composites of recurrent HF or cardiac death, were determined.
RESULTS: Seventy-seven cardiac events (28 cardiac deaths, 49 recurrent HFs)
occurred over two years. The events group revealed higher levels of Cys-C, UA,
and NT-proBNP. They showed increased blood urea nitrogen and creatinine, reduced
septal tissue Doppler velocity (TVI-Sm), and low frequencies of beta-blockers
(BB), diuretics and angiotensin-converting enzyme inhibitors/-receptor blockers.
Cys-C (the best cutoff: 1.7 mg/l) had a steady, persistent hazard ratio (HR) over
two years. On multivariate analysis, Cys-C, TVI-Sm, and BB were significant
predictors for adverse events. Cys-C provided an incremental value for prognosis
more than NT-proBNP and UA did over the follow-up period. CONCLUSIONS: Compared
with UA and NT-proBNP, Cys-C could be better prognostic biomarker for cardiac
events two years after acute HF.
PMID- 27494364
TI - Enhanced exercise and regenerative capacity in a mouse model that violates size
constraints of oxidative muscle fibres.
AB - A central tenet of skeletal muscle biology is the existence of an inverse
relationship between the oxidative fibre capacity and its size. However,
robustness of this relationship is unknown. We show that superimposition of
Estrogen-related receptor gamma (Errgamma) on the myostatin (Mtn) mouse null
background (Mtn(-/-)/Errgamma(Tg/+)) results in hypertrophic muscle with a high
oxidative capacity thus violating the inverse relationship between fibre size and
oxidative capacity. We also examined the canonical view that oxidative muscle
phenotype positively correlate with Satellite cell number, the resident stem
cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn(-/
)/Errgamma(Tg/+) mouse showed satellite cell deficit which unexpectedly did not
affect muscle regeneration. These observations 1) challenge the concept of a
constraint between fibre size and oxidative capacity and 2) indicate the
important role of the microcirculation in the regenerative capacity of a muscle
even when satellite cell numbers are reduced.
PMID- 27494367
TI - Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions
show improved heat stability.
AB - Conventional adenovirus vectors harboring E1 or E3 deletions followed by the
insertion of an exogenous gene show considerably reduced virion stability. Here,
we report strategies to generate complete replication-competent Ad11p(RCAd11p)
vectors that overcome the above disadvantage. A GFP cassette was successfully
introduced either upstream of E1A or in the E3A region. The resulting vectors
showed high expression levels of the hexon and E1genes and also strongly induced
the cytopathic effect in targeted cells. When harboring oversized genomes, the
RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in
comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat
treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and
Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles
after heat treatment at 47 degrees C for 5h. Our results demonstrated that both
genome size and the insertion site in the viral genome affect virion stability.
PMID- 27494368
TI - Use of prasugrel in the setting of clopidogrel hypersensitivity: Case report and
systematic review of the literature.
AB - Allergic reactions to clopidogrel soon after coronary stent implantation pose an
important and challenging clinical problem. We describe a 44-year-old man who
developed a diffuse maculopapular rash four days after initiation of clopidogrel
with drug-eluting coronary stent placement. An initial treat-through strategy was
unsuccessful due to patient intolerance to corticosteroids. Because of persistent
hypersensitivity, clopidogrel was substituted with prasugrel which was continued
successfully for one year without reaction. A systematic review of the literature
was performed which identified 10 prior case reports of patients with clopidogrel
hypersensitivity who were subsequently treated with prasugrel. Patient
characteristics and clinical outcomes of these patients plus the current case
were reviewed. There were 9 men and 2 women with ages from 44 to 76 years. All
patients had undergone coronary stent procedures. Prasugrel was successfully used
without cross-reactivity in 9 of the 11 patients (82%). Cross-reactivity was
reported in two patients who developed hypersensitivity reactions to prasugrel
similar to those experienced on clopidogrel. In conclusion, prasugrel can be used
successfully in most patients with a history of clopidogrel hypersensitivity.
However, potential cross-reactivity between these two thienopyridines may occur
in some patients.
PMID- 27494369
TI - High negative pressure subcutaneous suction drain for managing debilitating
subcutaneous emphysema secondary to tube thoracostomy for an iatrogenic post
computed tomography guided transthoracic needle biopsy pneumothorax: Case report
and review of literature.
AB - INTRODUCTION: Subcutaneous emphysema is a common complication of tube
thoracostomy. Though self-limiting, it should be treated when it causes palpebral
closure, dyspnea, dysphagia or undue disfigurement resulting in anxiety and
distress to the patient. PRESENTATION OF CASE: A 72year old man who was a known
case of COPD on bronchodilators developed a large pneumothorax and respiratory
distress after a CT guided transthoracic lung biopsy done for a lung opacity
(approx. 3*3cm) at the right hilar region on Chest X-ray. Within 24h of an urgent
tube thoracostomy, patient developed intractable subcutaneous emphysema with
closure of palpebral fissure and dyspnea unresponsive to increasing suction on
chest tube. A subcutaneous fenestrated drain was placed mid-way between the
nipple and clavicle in the mid-clavicular line bilaterally. Continuous negative
suction (-150mmHg) resulted in immediate, sustained relief and complete
resolution within 5days. DISCUSSION: Extensive and debilitating SE (subcutaneous
emphysema) has to be treated promptly to relieve patient discomfort, dysphagia or
imminent respiratory compromise. A variety of treatment have been tried including
infraclavicular blow-hole incisions, subcutaneous drains +/- negative pressure
suction, fenestrated angiocatheters, Vacuum assisted dressings and increasing
suction on a pre-existing chest tube. We describe a high negative pressure
subcutaneous suction drain which provides immediate and sustained relief in
debilitating SE. CONCLUSION: Debilitating subcutaneous emphysema which causes
distress, anxiety, palpebral closure, dyspnoea or dysphagia requires
intervention. High negative pressure subcutaneous suction drain provides
immediate and sustained relief in extensive and debilitating SE.
PMID- 27494370
TI - Laparoscopic cholecystectomy in a 2 year old male child with choleilithiasis and
recurrent right hypochondrial pain: Case report and review of literature.
AB - INTRODUCTION: Gallstone disease has been considered an uncommon entity in
children and infants, but its incidence is reportedly increasing which may be
attributed to widespread use of diagnostic imaging (ultrasonography).
PRESENTATION OF CASE: An apparently healthy 2 year old male child presented to
our Outpatient department with chief complaint of recurrent abdominal pain. The
episodes of pain were acute in onset and associated with vomiting. As per the
complete examination and findings, a diagnosis of chronic calculous cholecystitis
was made. A four port laparoscopic cholecystectomy was done. DISCUSSION: The
incidence of gallstones in children in India has not been sufficiently studied.
The incidence of gallstone disease in India was found to be 0.3% with the
incidence in age group 0-10 being less than 0.1%. In contrast to adult gallstone
disease, it has been found that there is no female preponderance in gallstone
diseases of infancy. Also, the majority of children having increased haemoglobin
turnover develop pigment stones only after 5 years of age. CONCLUSION: The
probability of gallstone disease in infants and young children should not be
ignored. Gall stones should always be considered as a differential diagnosis when
young patients present with complaints of abdominal pain.
PMID- 27494371
TI - Dermatofibrosarcoma protuberans post basal cell carcinoma excision: A case
report.
AB - INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare, malignant, soft
tissue neoplasm of the dermis. Tumor recurrence is common following resection,
and can be locally devastating if not identified in a timely manner. We report a
unique case of this rare tumor. This case poses the question of an association
between basal cell carcinoma (BCC) and DFSP, and presents the possible need for
increased awareness of DFSP for healthcare providers and patients with a history
of non-melanoma skin cancers as well as surgical or burn scars. PRESENTATION OF
CASE: A 77-year-old male with a history of surgical excision of BCC presented
with several palpable lesions in the superficial cutaneous tissue of the right
anterior abdominal wall. Most of the lesions were consistent with lipoma;
however, one lesion near the excision site of the BCC was more solid in
consistency. The mass was removed with wide local excision encompassing all
layers down to the abdominal fascia. Subsequent pathology findings included CD34
positive spindle cells in a whorled pattern consistent with DFSP. Resection
margins were positive and a wide re-excision was performed with margins being
negative. DISCUSSION: DFSP comprises approximately 0.01% of all malignant tumors.
There are no known precipitating factors of DFSP, but its presence in surgical
and burn scars is not uncommon. An association between DFSP and basal cell
carcinoma has been suggested in the literature. Dermatofibroma and rarely DFSP
may demonstrate basaloid proliferation of the overlying epidermis with
characteristics of BCC. One case reporting coexistent DFSP and BCC located to the
ear also suggested an association, but concluded that the finding was likely
incidental due to sun exposure. In our case, the lesion's location is less
routinely subjected to sun exposure and points more towards a possible
association. The mainstay of treatment for local DFSP is wide local excision.
Negative margins with the removal of fascia and muscle tissue as necessary is
essential and the most significant prognostic factor. Three-dimensional
reconstructions of DFSP have shown villous finger like projections of primary
tumors, which is believed to be responsible for local recurrence. Recurrence can
be devastating, as several cases have demonstrated rapid growth of remaining
cells with increased morbidity following further resection. CONCLUSION: Based on
this case and those found in the literature, we believe an association may exist
between DFSP and BCC and further study of this association is needed. DFSP is a
rare malignancy unknown to many healthcare providers, but in the presence of
increased awareness and physician vigilance in surgical resection and follow up,
the potential morbidity of DFSP may be prevented.
PMID- 27494372
TI - Diagnostic and therapeutic dilemmas in intra-abdominal desmoid tumors: A case
report and literature review.
AB - INTRODUCTION: Intra-abdominal desmoid tumors (DTs) are a rare and anatomically
diverse group of locally-aggressive, benign neoplasms. They are often difficult
to diagnose, even in patients who possess risk factors for the disease. Even
after a diagnosis has been reached, the optimal therapy is often not well
defined. PRESENTATION OF CASE: The case discussed of a 33-year old male with a
giant intra-abdominal desmoid is an example of both the diagnostic and
therapeutic dilemmas that arise when confronted with a patient with a DT. Initial
confusion over diagnosis led to ineffective therapy, but once the correct
diagnosis was made, the patient went on to definitive surgical resection.
DISCUSSION: The differential diagnosis of DTs is broad, and the diagnosis is
often delayed due to nonspecific presentations. Immunohistochemistry is crucial
in the accurate histological diagnosis, which guides treatment. Chemotherapy and
radiation have a role in the management of both primary and recurrent lesions,
but surgical resection remains the cornerstone of treatment. CONCLUSION: DTs
present a clinical challenge in their diagnosis and management, and despite
providing standard medical and surgical treatment, recurrence rates are high and
continued surveillance is crucial.
PMID- 27494373
TI - Abdominal trauma leading to diagnosis of Crohn's disease.
PMID- 27494374
TI - Erratum.
PMID- 27494375
TI - Motor versus body awareness: Voxel-based lesion analysis in anosognosia for
hemiplegia and somatoparaphrenia following right hemisphere stroke.
AB - Anosognosia for hemiplegia (AHP) is informative about the neurocognitive basis of
motor awareness. However, it is frequently associated with concomitant symptoms,
such as hemispatial neglect and disturbances in the sense of body ownership
(DSO). Although double dissociations between these symptoms have been reported,
there is ongoing debate about whether they are manifestations of independent
abnormalities, or a single neurocognitive deficit. We aimed to investigate the
specificity of lesions associated with AHP by surpassing four, existing
methodological limitations: (a) recruit a relatively large sample of patients
(total N = 70) in a multi-centre study; (b) identify lesions associated with AHP
in grey and white matter using voxel-based methods; (c) take into account the
duration of AHP and concomitant neglect symptoms; and (d) compare lesions against
a control hemiplegic group, patients suffering from AHP and DSO, and a few, rare
patients with selective DSO. Results indicated that acute AHP is associated with
a wide network, mainly including: (1) the Rolandic operculum, (2) the insula and
(3) the superior temporal gyri. Subcortically, damage mainly involved the basal
ganglia and white matter, mostly the superior corona radiate, arcuate fasciculus
and the part of the ventral, superior longitudinal fasciculus. Persistent
symptoms were linked with wider damage involving fronto-temporal cortex and long
white matter tracts. A shift in the latero-medial direction (mainly involving the
basal ganglia and surrounding white matter) emerged when DSO was taken accounted
for. These results suggest that while bodily awareness is processed by areas
widely distributed across the brain, intact subcortical structures and white
matter tracts may be necessary to support basic feelings of owning and
controlling contralateral body parts. An accurate and 'up-to-date' awareness of
our motor abilities, however, may rely also on intact processing in cortical
areas which presumably allow higher-order inferences about the current state of
the body.
PMID- 27494376
TI - Temporal subtraction contrast-enhanced dedicated breast CT.
AB - The development of a framework of deformable image registration and segmentation
for the purpose of temporal subtraction contrast-enhanced breast CT is described.
An iterative histogram-based two-means clustering method was used for the
segmentation. Dedicated breast CT images were segmented into background (air),
adipose, fibroglandular and skin components. Fibroglandular tissue was classified
as either normal or contrast-enhanced then divided into tiers for the purpose of
categorizing degrees of contrast enhancement. A variant of the Demons deformable
registration algorithm, intensity difference adaptive Demons (IDAD), was
developed to correct for the large deformation forces that stemmed from contrast
enhancement. In this application, the accuracy of the proposed method was
evaluated in both mathematically-simulated and physically-acquired phantom
images. Clinical usage and accuracy of the temporal subtraction framework was
demonstrated using contrast-enhanced breast CT datasets from five patients.
Registration performance was quantified using normalized cross correlation (NCC),
symmetric uncertainty coefficient, normalized mutual information (NMI), mean
square error (MSE) and target registration error (TRE). The proposed method
outperformed conventional affine and other Demons variations in contrast enhanced
breast CT image registration. In simulation studies, IDAD exhibited improvement
in MSE (0-16%), NCC (0-6%), NMI (0-13%) and TRE (0-34%) compared to the
conventional Demons approaches, depending on the size and intensity of the
enhancing lesion. As lesion size and contrast enhancement levels increased, so
did the improvement. The drop in the correlation between the pre- and post
contrast images for the largest enhancement levels in phantom studies is less
than 1.2% (150 Hounsfield units). Registration error, measured by TRE, shows only
submillimeter mismatches between the concordant anatomical target points in all
patient studies. The algorithm was implemented using a parallel processing
architecture resulting in rapid execution time for the iterative segmentation and
intensity-adaptive registration techniques. Characterization of contrast-enhanced
lesions is improved using temporal subtraction contrast-enhanced dedicated breast
CT. Adaptation of Demons registration forces as a function of contrast
enhancement levels provided a means to accurately align breast tissue in pre- and
post-contrast image acquisitions, improving subtraction results. Spatial
subtraction of the aligned images yields useful diagnostic information with
respect to enhanced lesion morphology and uptake.
PMID- 27494377
TI - Synthesis and characterization of Cu-Zn/TiO2 for the photocatalytic conversion of
CO2 to methane.
AB - Different Cu-Zn/TiO2 catalysts were synthesized by using the wet impregnation
method. The prepared catalysts were used for the conversion of CO2 into methane
by photocatalysis. Various characterization techniques were used to observe the
surface morphology, crystalline phase, Brunauer-Emmett-Teller (BET) surface area,
presence of impregnated Cu and Zn, and functional group. Scanning electron
microscope analysis showed spherical morphology, and slight agglomeration of
catalyst particles was observed. BET analysis revealed that the surface area of
the catalyst was decreased from 10 to 8.5 m2/g after impregnation of Cu and Zn
over TiO2 support. Synergetic effect of Cu and Zn over TiO2 support (Cu2.6/TiO2,
Zn0.5/TiO2 and Cu2.6-Zn0.5/TiO2) and the effects of Cu loading (0, 1.8, 2.1, 2.6
and 2.9 wt%) were also investigated at different feed molar ratios of H2/CO2 (2:1
and 4:1). The Cu2.6-Zn0.5/TiO2 catalyst showed a maximum conversion of 14.3% at a
feed molar ratio of 4. The addition of Zn over the catalyst surface increased the
conversion of CO2 from 10% to 14.3% which might be due to synergy of Cu and Zn
over TiO2 support.
PMID- 27494378
TI - Influence of Sodium Cationization versus Protonation on the Gas-Phase
Conformations and Glycosidic Bond Stabilities of 2'-Deoxyadenosine and Adenosine.
AB - The influence of noncovalent interactions with a sodium cation on the gas-phase
structures and N-glycosidic bond stabilities of 2'-deoxyadenosine (dAdo) and
adenosine (Ado), [dAdo+Na](+) and [Ado+Na](+), are probed via infrared multiple
photon dissociation (IRMPD) action spectroscopy and energy-resolved collision
induced dissociation (ER-CID) experiments. ER-CID experiments are also performed
on the protonated forms of these nucleosides, [dAdo+H](+) and [Ado+H](+), for
comparison purposes. Complementary electronic structure calculations are
performed to determine the structures and relative stabilities of the stable low
energy conformations of the sodium cationized nucleoside complexes and to predict
their IR spectra. Comparison between the measured IRMPD action spectra and
calculated IR spectra enables the conformations of the sodium cationized
nucleosides present in the experiments to be elucidated. The influence of sodium
cationization versus protonation on the structures and IR spectra is elucidated
by comparison to IRMPD and theoretical results previously reported for the
protonated forms of these nucleosides. The influence of sodium cationization
versus protonation on the glycosidic bond stability of the adenine nucleosides is
determined by comparison of the ER-CID behavior of these systems. All structures
present in the experiments are found to involve tridentate binding of Na(+) to
the N3, O4', and O5' atoms forming favorable 5- and 6-membered chelation rings,
which requires that adenine rotate to a syn configuration. This mode of sodium
cation binding results in moderate flexibility of the sugar moiety such that the
sugar puckering of the conformations present varies between C2'-endo and O4'
endo. Sodium cationization is found to be less effective toward activating the N
glycosidic bond than protonation for both dAdo and Ado. Both the IRMPD yields and
ER-CID behavior indicate that the 2'-hydroxyl substituent of Ado stabilizes the N
glycosidic bond relative to that of dAdo.
PMID- 27494379
TI - Dialysis: the best quality at the lowest cost.
PMID- 27494380
TI - Whole-Exome-Sequencing Reveals Small Deletions in CASP14 in Patients with
Autosomal Recessive Inherited Ichthyosis.
PMID- 27494382
TI - Bilateral Outer Retinal Necrosis Following Mumps Infection.
PMID- 27494383
TI - A Concise Approach to Site-Specific Topological Protein-Poly(amino acid)
Conjugates Enabled by in Situ-Generated Functionalities.
AB - Controlling the topology of polymer-modified proteins has attracted growing
interest. However, one of the main challenges in this field is the lack of
efficient and site-specific methods for installing multiple bioorthogonal
functionalities on substrate polymers. We report here an orchestrating strategy
that provides easy access to various topological protein-poly(amino acid) (PAA)
conjugates in high yields. This method features the in situ installation of two
"chemical handles", including a thioester for native chemical ligation and a
polyglycine nucleophile for sortase A-mediated ligation, at both ends of
substrate PAAs. As a result, neither pre-functionalization of initiator or
monomer units, nor post-polymerization modification of the resultant polymers, is
necessary. Site-specific topological conjugates, particularly circular
conjugates, can be conveniently synthesized under mild conditions from the
functionalized PAAs. The biomedical utility of our method is demonstrated by the
rapid and efficient generation of several therapeutic interferon-alpha
conjugates, which exhibit significantly enhanced protease resistance and
thermostability. Given the versatility of both PAAs and proteins, the method
offers a convenient approach to producing libraries of conjugates for biological
applications.
PMID- 27494381
TI - Biology and biogenesis of shed microvesicles.
AB - The ability of cells to transmit bioactive molecules to recipient cells and the
extracellular environment is a fundamental requirement for both normal physiology
and disease pathogenesis. It has traditionally been thought that soluble factors
released from cells were responsible for this cellular signaling but recent
research has revealed a fundamental role for microvesicles in this process.
Microvesicles are heterogeneous membrane-bound sacs that are shed from the
surface of cells into the extracellular environment in a highly regulated
process. They are shed following the selective incorporation of a host of
molecular cargo including multiple types of proteins and nucleic acids. In
addition to providing new insight into the etiology of complex human diseases,
microvesicles also show great promise as a tool for advanced diagnosis and
therapy as we move forward into a new age of personalized medicine. Here we
review current status of the rapidly evolving field of microvesicle biology,
highlighting critical regulatory roles for several small GTPases in the biology
and biogenesis of shed microvesicles.
PMID- 27494384
TI - Equation of state and thermodynamic Gruneisen parameter of monoclinic 1,1-diamino
2,2-dinitroethylene.
AB - In situ synchrotron x-ray diffraction experiments were conducted on 1,1-diamino
2,2-dinitroethylene (FOX-7) at pressures up to 6.8 GPa and temperatures up to 485
K. Within the resolution of the present diffraction data, our results do not
reveal evidence for a pressure-induced structural phase transition near 2 GPa,
previously observed in several vibrational spectroscopy experiments. Based on
unit-cell volume measurements, the least-squares fit using the third-order Birch
Murnaghan equation of state (EOS) yields K 0 = 12.6 +/- 1.4 GPa and [Formula:
see text] = 11.3 +/- 2.1 for the alpha-phase of FOX-7, which are in good
agreement with recently reported values for the deuterated sample, indicating
that the effect of hydrogen-deuterium substitution on the compressibility of FOX
7 is negligibly small. A thermal EOS is also obtained for the alpha-phase of FOX
7, including pressure dependence of thermal expansivity, (?alpha/?P)T = -7.0
+/- 2.0 * 10(-5) K(-1) GPa(-1), and temperature derivative of the bulk
modulus, (?K T/?T)P = -1.1 * 10(-2) GPa K(-1). From these EOS parameters, we
calculate heat capacity at constant volume (C V) and thermodynamic Gruneisen
parameter (gamma TH) as a function of temperature. At ambient conditions, the
calculated gamma TH is 1.055, which is in good agreement with the value (1.09)
previously obtained from density functional theory (DFT). The obtained C V,
however, is 13% larger than that calculated from the first-principles
calculations, indicating that the dispersion correction in the DFT calculations
may need to be further improved for describing intermolecular interactions of
molecular crystals.
PMID- 27494385
TI - Biodegradation of 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (DDT) by using
Serratia marcescens NCIM 2919.
AB - A solvent tolerant bacterium Serratia marcescens NCIM 2919 has been evaluated for
degradation of DDT (1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane). The
bacterium was able to degrade up to 42% of initial 50 mg L-1 of DDT within 10
days of incubation. The highlight of the work was the elucidation of DDT
degradation pathway in S. marcescens. A total of four intermediates metabolites
viz. 2,2-bis (chlorophenyl)-1,1-dichloroethane (DDD), 2,2-bis (chlorophenyl)-1,1
dichloroethylene (DDE), 2,2-bis (chlorophenyl)-1-chloroethylene (DDMU), and 4
chlorobenzoic acid (4-CBA) were identified by GC-Mass and FTIR. 4-CBA was found
to be the stable product of DDT degradation. Metabolites preceding 4-CBA were not
toxic to strain as reveled through luxuriant growth in presence of varying
concentrations of exogenous DDD and DDE. However, 4-CBA was observed to inhibit
the growth of bacterium. The DDT degrading efficiency of S. marcescens NCIM 2919
hence could be used in combination with 4-CBA utilizing strains either as binary
culture or consortia for mineralization of DDT. Application of S. marcescens NCIM
2919 to DDT contaminated soil, showed 74.7% reduction of initial 12.0 mg kg-1 of
DDT after 18-days of treatment.
PMID- 27494387
TI - Obesity: BMI-increasing variant identified in Samoans.
PMID- 27494386
TI - Frostbite: Spectrum of Imaging Findings and Guidelines for Management.
AB - Frostbite is a localized cold thermal injury that results from tissue freezing.
Frostbite injuries can have a substantial effect on long-term limb function and
mobility if not promptly evaluated and treated. Imaging plays a critical role in
initial evaluation of frostbite injuries and in monitoring response to treatment.
A multimodality approach involving radiography, digital subtraction angiography
(DSA), and/or multiphase bone scintigraphy with hybrid single photon emission
computed tomography (SPECT)/computed tomography (CT) is often necessary for
optimal guidance of frostbite care. Radiographs serve as an initial survey of the
affected limb and may demonstrate characteristic findings, depending on the time
course and severity of injury. DSA is used to evaluate perfusion of affected soft
tissues and identify potential targets for therapeutic intervention. Angiography
directed thrombolysis plays an essential role in tissue preservation and salvage
in deep frostbite injuries. Multiphase bone scintigraphy with technetium 99m
labeled diphosphonate provides valuable information regarding the status of
tissue viability after initial treatment. The addition of SPECT/CT to multiphase
bone scintigraphy enables precise anatomic localization of the level and depth of
tissue necrosis before its appearance at physical examination and can help
uncover subtle findings that may remain occult at scintigraphy alone. Multiphase
bone scintigraphy with SPECT/CT is the modality of choice for prognostication and
planning of definitive surgical care of affected limbs. Appropriate use of
imaging to direct frostbite care can help limit the effects that these injuries
have on limb function and mobility. (c)RSNA, 2016.
PMID- 27494388
TI - Diabetes: Natural autoantibodies protect against T1DM.
PMID- 27494389
TI - Parathyroid gland: GNAS defects in a large PHP cohort.
PMID- 27494390
TI - Thyroid cancer: Mortality unaffected by rise in use of imaging tests.
PMID- 27494391
TI - Vitamin D and falls - the dosage conundrum.
AB - Falls are a major health problem in elderly individuals. Although intensive
physical therapy and management of hazards in the home can reduce falls by 25%,
long-term practicality limits their use. Interest in vitamin D as a medical
therapy has led to many trials; however, results using daily oral doses of
vitamin D have been inconsistent. In the past 5 years, studies on the effect of
bolus doses of vitamin D have produced surprising results. Bolus doses of vitamin
D, given annually (at a dose of 300,000 IU or 500,000 IU) or monthly (at a dose
of 24,000 IU or 60,000 IU) - equivalent to approximate daily doses of 800 IU,
1400 IU and 2,000 IU - result in a significant increase in the number of falls
and fractures associated with serum levels of 25-hydroxyvitamin D greater than 40
45 ng/ml (equivalent to 100-112 nmol/l). These unexpected results show increased
falls and fractures are adverse events related to vitamin D administration. Until
further safety data is available, bolus dosing or daily doses should not exceed
3,000 IU and serum levels of 25-hydroxyvitamin D should not exceed 40-45 ng/ml
(equivalent to 100-112 nmol/l) in elderly individuals.
PMID- 27494392
TI - Magnetic Materials for the Selective Analysis of Peptide and Protein Biomarkers.
AB - This mini-review article provides an overview on the use of magnetic materials
for the analysis of protein biomarkers. In particular, the advantage provided by
magnetic solid phase extraction will be discussed with selected examples,
considering untargeted analysis for screening new biomarker proteins and targeted
investigation on known and suggested new biomarkers. Aspects, such as enrichment
efficiency over conventional techniques, ease of use, functionalization
versatility and automation will be considered, together with quantification and
deeper structure elucidation provided by coupling selective or specific
enrichment to powerful characterization techniques, such as mass spectrometry.
PMID- 27494393
TI - New therapeutic property of Dimebon as a neuroprotective agent.
AB - Dimebon (or Latrepirdine) was initially used as an anti-histamergic drug but
later new therapeutic properties were rediscovered, adding to a growing body of
"old" agents with prominent neuroprotective effects. In the present manuscript,
we are focusing on our latest study on Dimebon with regard to brain"s
pathological processes using in vivo proteinopathy models. In the study,
neurodegenerative pathology has been attributed to a group of aggregate-prone
proteins: hyperphosphorylated tau, fused in sarcoma and gamma-synuclein , which
are involved in a number of neurological disorders. We have also presented our in
vitro model based on overexpression of an aberrant mutant form of transactive
response DNA binding 43 kDa protein in cultured SH-SY5Y neuroblastoma cells.
Dimebon treatment followed by the activation of autophagy markers resulted in
reduced number of inclusion containing cells. The most significant effects of
Dimebon appeared to be on the improving cellular energy balance, mitochondria
stability by increasing the threshold for nonselective mitochondrial pore opening
as well as on increased calcium retention capacity while reducing lipid
peroxidation. The therapeutic potential of Dimebon and newly designed analogs
show disease modifying properties and could be used to treat neurodegenerative
disorders. In addition, new data hint on a possible anti-aging effect and
potential application of Dimebon for treatment of anxiety, ischemia and
depression. Overall, our findings suggest that the most pronounced effect of
Dimebon was observed when treatment was started at the early stages of disease
onset and this factor needs to be taken into account while planning future
clinical trials.
PMID- 27494394
TI - Clinical Impact Research - how to choose experimental or observational
intervention study?
AB - BACKGROUND: Interventions directed to individuals by health and social care
systems should increase health and welfare of patients and customers. AIMS: This
paper aims to present and define a new concept Clinical Impact Research (CIR) and
suggest which study design, either randomized controlled trial (RCT)
(experimental) or benchmarking controlled trial (BCT) (observational) is
recommendable and to consider the feasibility, validity, and generalizability
issues in CIR. METHODS: The new concept is based on a narrative review of the
literature and on author's idea that in intervention studies, there is a need to
cover comprehensively all the main impact categories and their respective
outcomes. The considerations on how to choose the most appropriate study design
(RCT or BCT) were based on previous methodological studies on RCTs and BCTs and
on author's previous work on the concepts benchmarking controlled trial and
system impact research (SIR). RESULTS: The CIR covers all studies aiming to
assess the impact for health and welfare of any health (and integrated social)
care or public health intervention directed to an individual. The impact
categories are accessibility, quality, equality, effectiveness, safety, and
efficiency. Impact is the main concept, and within each impact category, both
generic- and context-specific outcome measures are needed. CIR uses RCTs and
BCTs. CONCLUSIONS: CIR should be given a high priority in medical, health care,
and health economic research. Clinicians and leaders at all levels of health care
can exploit the evidence from CIR. Key messages The new concept of Clinical
Impact Research (CIR) is defined as a research field aiming to assess what are
the impacts of healthcare and public health interventions targeted to patients or
individuals. The term impact refers to all effects caused by the interventions,
with particular emphasis on accessibility, quality, equality, effectiveness,
safety, and efficiency. CIR uses two study designs: randomized controlled trials
(RCTs) (experimental) and benchmarking controlled trials (BCTs) (observational).
Suggestions on how to choose between RCT and BCT as the most suitable study
design are presented. Simple way of determining the study question in CIR based
on the PICO (patient, intervention, control intervention, outcome) framework is
presented. CIR creates the scientific basis for clinical decisions. Clinicians
and leaders at all levels of health care and those working for public health can
use the evidence from CIR for the benefit of patients and the population.
PMID- 27494395
TI - (15)N NMR Spectroscopy, X-ray and Neutron Diffraction, Quantum-Chemical
Calculations, and UV/vis-Spectrophotometric Titrations as Complementary
Techniques for the Analysis of Pyridine-Supported Bicyclic Guanidine Superbases.
AB - Pyridine substituted with one and two bicyclic guanidine groups has been studied
as a potential source of superbases. 2-{hpp}C5H4N (I) and 2,6-{hpp}2C5H3N (II)
(hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) were protonated using
[HNEt3][BPh4] to afford [I-H][BPh4] (1a), [II-H][BPh4] (2), and [II-H2][BPh4]2
(3). Solution-state (1)H and (15)N NMR spectroscopy shows a symmetrical cation in
2, indicating a facile proton-exchange process in solution. Solid-state (15)N NMR
data differentiates between the two groups, indicating a mixed
guanidine/guanidinium. X-ray diffraction data are consistent with protonation at
the imine nitrogen, confirmed for 1a by single-crystal neutron diffraction. The
crystal structure of 1a shows association of two [I-H](+) cations within a cage
of [BPh4](-) anions. Computational analysis performed in the gas phase and in
MeCN solution shows that the free energy barrier to transfer a proton between
imino centers in [II-H](+) is 1 order of magnitude lower in MeCN than in the gas
phase. The results provide evidence that linking hpp groups with the pyridyl
group stabilizes the protonation center, thereby increasing the intrinsic
basicity in the gas phase, while the bulk prevents efficient cation solvation,
resulting in diminished pKa(MeCN) values. Spectrophotometrically measured pKa
values are in excellent agreement with calculated values and confirm that I and
II are superbases in solution.
PMID- 27494396
TI - Patient and Family Member-Led Research in the Intensive Care Unit: A Novel
Approach to Patient-Centered Research.
AB - INTRODUCTION: Engaging patients and family members as partners in research
increases the relevance of study results and enhances patient-centered care; how
to best engage patients and families in research is unknown. METHODS: We tested a
novel research approach that engages and trains patients and family members as
researchers to see if we could understand and describe the experiences of
patients admitted to the intensive care unit (ICU) and their families. Former
patients and family members conducted focus groups and interviews with patients
(n = 11) and families of surviving (n = 14) and deceased (n = 7) patients from 13
ICUs in Alberta Canada, and analyzed data using conventional content analysis.
Separate blinded qualitative researchers conducted an independent analysis.
RESULTS: Participants described three phases in the patient/family "ICU journey";
admission to ICU, daily care in ICU, and post-ICU experience. Admission to ICU
was characterized by family shock and disorientation with families needing the
presence and support of a provider. Participants described five important
elements of daily care: honoring the patient's voice, the need to know, decision
making, medical care, and culture in ICU. The post-ICU experience was
characterized by the challenges of the transition from ICU to a hospital ward and
long-term effects of critical illness. These "ICU journey" experiences were
described as integral to appropriate interactions with the care team and comfort
and trust in the ICU, which were perceived as essential for a community of
caring. Participants provided suggestions for improvement: 1) provide a dedicated
family navigator, 2) increase provider awareness of the fragility of family
trust, 3) improve provider communication skills, 4) improve the transition from
ICU to hospital ward, and 5) inform patients about the long-term effects of
critical illness. Analyses by independent qualitative researchers identified
similar themes. CONCLUSIONS: Patient and family member-led research is feasible
and can identify opportunities for improving care.
PMID- 27494397
TI - Genome-Wide Association Study for Indicator Traits of Sexual Precocity in Nellore
Cattle.
AB - The objective of this study was to perform a genome-wide association study (GWAS)
to detect chromosome regions associated with indicator traits of sexual precocity
in Nellore cattle. Data from Nellore animals belonging to farms which participate
in the DeltaGen(r) and Paint(r) animal breeding programs, were used. The traits
used in this study were the occurrence of early pregnancy (EP) and scrotal
circumference (SC). Data from 72,675 females and 83,911 males with phenotypes
were used; of these, 1,770 females and 1,680 males were genotyped. The SNP
effects were estimated with a single-step procedure (WssGBLUP) and the observed
phenotypes were used as dependent variables. All animals with available genotypes
and phenotypes, in addition to those with only phenotypic information, were used.
A single-trait animal model was applied to predict breeding values and the
solutions of SNP effects were obtained from these breeding values. The results of
GWAS are reported as the proportion of variance explained by windows with 150
adjacent SNPs. The 10 windows that explained the highest proportion of variance
were identified. The results of this study indicate the polygenic nature of EP
and SC, demonstrating that the indicator traits of sexual precocity studied here
are probably controlled by many genes, including some of moderate effect. The 10
windows with large effects obtained for EP are located on chromosomes 5, 6, 7,
14, 18, 21 and 27, and together explained 7.91% of the total genetic variance.
For SC, these windows are located on chromosomes 4, 8, 11, 13, 14, 19, 22 and 23,
explaining 6.78% of total variance. GWAS permitted to identify chromosome regions
associated with EP and SC. The identification of these regions contributes to a
better understanding and evaluation of these traits, and permits to indicate
candidate genes for future investigation of causal mutations.
PMID- 27494398
TI - Trend in and predictors for cardiovascular mortality in patients with rheumatoid
arthritis over a period of 15 years: a prospective cohort study.
AB - OBJECTIVES: To investigate a) the cardiovascular (CV) mortality in a clinical
cohort of patients with established rheumatoid arthritis (RA) in comparison with
the general population over 15 years, b) the trend in this CV mortality during
the study period, and c) for a broad range of predictors, which baseline
variables predict CV mortality. METHODS: In 1997, a sample of 1222 patients was
randomly selected from the register of a rheumatology outpatient clinic in
Amsterdam. Their CV mortality between 1997 and 2012 was obtained from Statistics
Netherlands. The standardised mortality ratio (SMR) for CV mortality was
calculated. A linear poisson regression analysis was performed to investigate if
there was a trend in SMR over time. A Cox regression analysis was performed to
determine which baseline variables predicted CV mortality. RESULTS: Mean age of
the population at baseline was 60.4 (SD 15.4) years and 72.6% of the patients
were women. Estimated SMR (95% confidence interval) for CV mortality was 1.24
(1.05, 1.43). The SMR decreased with 3% annually (p=0.16). Higher age, higher
erythrocyte sedimentation rate, having CV comorbidity and diabetes mellitus (DM)
were predictors for CV mortality. CONCLUSIONS: CV mortality among patients with
RA in the past 15 years was still higher than in the general population. CV
mortality decrease was not statistically significant. As CV mortality in RA is
still higher than in the general population, continued attention for CV diseases
in RA is important. Both tight control of disease activity and good care for
comorbid conditions (CV diseases and DM) are advocated.
PMID- 27494400
TI - Following [FeFe] Hydrogenase Active Site Intermediates by Time-Resolved Mid-IR
Spectroscopy.
AB - Time-resolved nanosecond mid-infrared spectroscopy is for the first time employed
to study the [FeFe] hydrogenase from Chlamydomonas reinhardtii and to investigate
relevant intermediates of the enzyme active site. An actinic 355 nm, 10 ns laser
flash triggered photodissociation of a carbonyl group from the CO-inhibited state
Hox-CO to form the state Hox, which is an intermediate of the catalytic proton
reduction cycle. Time-resolved infrared spectroscopy allowed us to directly
follow the subsequent rebinding of the carbonyl, re-forming Hox-CO, and determine
the reaction half-life to be t1/2 ~ 13 +/- 5 ms at room temperature. This gives
direct information on the dynamics of CO inhibition of the enzyme.
PMID- 27494399
TI - Are short (blue) wavelengths necessary for light treatment of seasonal affective
disorder?
AB - Despite widely published speculation regarding a potential potency advantage of
short-wavelength (blue-appearing) light for Seasonal Affective Disorder (SAD)
treatment, there have been few systematic studies. Those comparing short
wavelength to broad-wavelength (white) light under actual clinical conditions
suggest equivalent effectiveness. This multicenter, parallel-group design trial
was undertaken to compare the effects of light therapy on SAD using blue (~465
nm) versus blue-free (595-612 nm) LED lights. Fifty-six medication-free subjects
aged 21-64 years who met DSM-IV-TR criteria for recurrent major depression with
winter-type seasonal pattern were enrolled in this blinded study at five
participating centers between January and March 2012. Thirty-five subjects met
the criteria for randomization to 30 min of either blue (~465 nm) or blue-free
(595-612 nm) daily morning light therapy. Twenty-nine subjects completed the
study; three subjects withdrew due to treatment-related adverse events, including
migraines, and three withdrew for non-study-related reasons. The primary
effectiveness variable was depression score (SIGH-ADS) after six weeks of daily
light treatment. Secondary effectiveness variables included quality-of-life (QoL)
and suicidality ratings. Using an intent-to-treat analysis, mean depression
scores were different at baseline for the blue group (29 +/- 5 versus 26 +/- 5, p
= 0.05 blue versus blue-free, respectively), and the initial score was used as a
covariate. Baseline scores were not significantly different between treatment
groups among those who completed the study, and no significant differences in
depression scores were observed after 6 weeks (mean +/- SD scores at 6 weeks: 5.6
+/- 6.1 versus 4.5 +/- 5.3, p = 0.74, blue versus blue-free, respectively). In
addition, the proportion of subjects who met remission criteria, defined as a
depression score <=8, was not significantly different between the two groups (p =
0.41); among the 29 subjects who completed the study, 76% of subjects experienced
remission by the end of the trial, which coincided with the beginning of spring.
The QoL and suicidality ratings were also significantly improved from pre- to
post-treatment, with no significant difference between treatments. No subject
experienced worsening or non-improved symptoms over the 6-week trial. The main
finding of this study is that subjects treated with blue light did not improve
more than subjects treated with blue-free light; both showed substantial
improvement on multiple measures. Failure to find differences may have resulted
from methodological constraints, including a small sample size. Recruitment began
mid-winter during an unusually mild season, and the trial was terminated earlier
than planned by the study sponsor due to a failure to detect a difference.
However, if confirmed in a larger randomized sample, these results suggest that
blue wavelengths are not necessary for successful SAD treatment.
PMID- 27494401
TI - Identifying the Dominant Personality Profiles in Medical Students: Implications
for Their Well-Being and Resilience.
AB - PURPOSE: There is a high prevalence of stress, depression, and burn-out in
medical students. Medical students differ widely in personality traits, self
perceptions, and values that may have an impact on their well-being. This study
aimed to investigate variability in their personality profiles in relation to
their potential for well-being and resilience. METHOD: Participants were 808
medical students from The University of Queensland. An online questionnaire
collected socio-demographics and the Temperament and Character Inventory to
assess personality traits. Latent profile analyses identified students' trait
profiles. RESULTS: Two distinct personality profiles were identified. Profile 1
("Resilient") characterized 60% of the sample and was distinguished by low Harm
Avoidance combined with very high Persistence, Self-Directedness and
Cooperativeness compared to Profile 2 ("Conscientious"). Both Profiles had
average levels of Reward Dependence and Novelty Seeking and low levels of Self
Transcendence. Profiles did not differ by age, gender, or country of birth, but
rural background students were more likely to have Profile 1. While both Profiles
indicate mature and healthy personalities, the combination of traits in Profile 1
is more strongly indicative of well-being and resilience. CONCLUSIONS: Finding
two distinct profiles of personality highlights the importance of considering
combinations of traits and how they may interact with medical students' potential
for well-being. Although both profiles of students show healthy personalities,
many may lack the resilience to maintain well-being over years of medical
training. Programs that develop character and personality self-awareness would
enhance their well-being and prepare them to promote the health of their
patients.
PMID- 27494402
TI - Detection of long non-coding RNAs in human breastmilk extracellular vesicles:
Implications for early child development.
AB - Breastmilk has many documented beneficial effects on the developing human infant,
but the components of breastmilk that influence these developmental pathways have
not been fully elucidated. Increasing evidence suggests that non-coding RNAs
encapsulated in extracellular vesicles (EVs) represent an important mechanism of
communication between the mother and child. Long non-coding RNAs (lncRNAs) are of
particular interest given their key role in gene expression and development.
However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR
to determine whether EVs isolated from human breastmilk contain lncRNAs
previously reported to be important for developmental processes. We detected 55
of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and
CRNDE, DANCR GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5,
SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho>0.9; P<0.0001),
which may indicate that the loading of these lncRNAs into breastmilk EVs is
regulated by the same pathways. The detected lncRNAs are important epigenetic
regulators involved in processes such as immune cell regulation and metabolism.
They may target a repertoire of recipient cells in offspring and could be
essential for child development and health. Further experimental and
epidemiological studies are warranted to determine the impact of breastmilk EV
encapsulated lnRNAs in mother to child signaling.
PMID- 27494404
TI - HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and
the Severity of Coronary Atherosclerosis in a Chinese Han Population.
AB - A previous genome-wide association study showed that a single nucleotide
polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated
with large artery stroke (LAS) in Caucasians. Based on the similar
atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we
aimed to evaluate the associations of SNP rs2107595 with CAD risk and the
severity of coronary atherosclerosis in a Chinese Han population, and explore the
potential gene-environment interactions among SNP rs2107595 and conventional CAD
risk factors. In a two-stage case-control study with a total of 2317 CAD patients
and 2404 controls, the AG + AA genotypes of SNP rs2107595 were significantly
associated with increased CAD risk (Adjusted odds ratio (OR) = 1.23, Padj =
0.001) and higher modified Gensini scores (Adjusted OR = 1.38, Padj < 0.001).
These associations remained significant in subtype analyses for unstable angina
pectoris (UAP), non-ST-segment elevation myocardial infarction (NSTEMI) and ST
segment elevation myocardial infarction (STEMI). Subgroup and multifactor
dimensionality reduction analyses (MDR) further found the gene-environment
interactions among SNP rs2107595, body mass index, type 2 diabetes and
hyperlipidemia in CAD risk and the severity of coronary atherosclerosis.
Moreover, patients with CAD had higher levels of HDAC9 mRNA expression and plasma
HDAC9 than controls. Subsequent genotype-phenotype analyses observed the
significant correlations of SNP rs2107595 with HDAC9 mRNA expression and plasma
HDAC9 levels in controls and patients with NSTEMI and STEMI. Taken together, our
data suggest that SNP rs2107595 may contribute to coronary atherosclerosis and
CAD risk through a possible mechanism of regulating HDAC9 expression and gene
environment interactions.
PMID- 27494406
TI - FITC Conjugation Markedly Enhances Hepatic Clearance of N-Formyl Peptides.
AB - In both septic and aseptic inflammation, N-formyl peptides may enter the
circulation and induce a systemic inflammatory response syndrome similar to that
observed during septic shock. The inflammatory response is brought about by the
binding of N-formyl peptide to formyl peptide receptors (FPRs), specific
signaling receptors expressed on myeloid as well as non-myeloid cells involved in
the inflammatory process. N-formyl peptides conjugated with fluorochromes, such
as fluorescein isothiocyanate (FITC) are increasingly experimentally used to
identify tissues involved in inflammation. Hypothesizing that the process of FITC
conjugation may transfer formyl peptide to a ligand that is efficiently cleared
from the circulation by the natural powerful hepatic scavenging regime we studied
the biodistribution of intravenously administered FITC-fNLPNTL (Fluorescein
isothiocyanate- N-Formyl-Nle-Leu-Phe-Nle-Tyr-Lys) in mice. Our findings can be
summarized as follows: i) In contrast to unconjugated fNLPNTL, FITC-fNLPNTL was
rapidly taken up in the liver; ii) Mouse and human liver sinusoidal endothelial
cells (LSECs) and hepatocytes express formyl peptide receptor 1 (FRP1) on both
mRNA (PCR) and protein (Western blot) levels; iii) Immunohistochemistry showed
that mouse and human liver sections expressed FRP1 in LSECs and hepatocytes; and
iv) Uptake of FITC-fNLPNTL could be largely blocked in mouse and human
hepatocytes by surplus-unconjugated fNLPNTL, thereby suggesting that the
hepatocytes in both species recognized FITC-fNLPNTL and fNLPNTL as
indistinguishable ligands. This was in contrast to the mouse and human LSECs, in
which the uptake of FITC-fNLPNTL was mediated by both FRP1 and a scavenger
receptor, specifically expressed on LSECs. Based on these results we conclude
that a significant proportion of FITC-fNLPNTL is taken up in LSECs via a
scavenger receptor naturally expressed in these cells. This calls for great
caution when using FITC-fNLPNTL and other chromogen-conjugated formyl peptides as
a probe to identify cells in a liver engaged in inflammation. Moreover, our
finding emphasizes the role of the liver as an important neutralizer of otherwise
strong inflammatory signals such as formyl peptides.
PMID- 27494403
TI - The Hippo Pathway Targets Rae1 to Regulate Mitosis and Organ Size and to Feed
Back to Regulate Upstream Components Merlin, Hippo, and Warts.
AB - Hippo signaling acts as a master regulatory pathway controlling growth,
proliferation, and apoptosis and also ensures that variations in proliferation do
not alter organ size. How the pathway coordinates restricting proliferation with
organ size control remains a major unanswered question. Here we identify Rae1 as
a highly-conserved target of the Hippo Pathway integrating proliferation and
organ size. Genetic and biochemical studies in Drosophila cells and tissues and
in mammalian cells indicate that Hippo signaling promotes Rae1 degradation
downstream of Warts/Lats. In proliferating cells, Rae1 loss restricts cyclin B
levels and organ size while Rae1 over-expression increases cyclin B levels and
organ size, similar to Hippo Pathway over-activation or loss-of-function,
respectively. Importantly, Rae1 regulation by the Hippo Pathway is crucial for
its regulation of cyclin B and organ size; reducing Rae1 blocks cyclin B
accumulation and suppresses overgrowth caused by Hippo Pathway loss.
Surprisingly, in addition to suppressing overgrowth, reducing Rae1 also
compromises survival of epithelial tissue overgrowing due to loss of Hippo
signaling leading to a tissue "synthetic lethality" phenotype. Excitingly, Rae1
plays a highly conserved role to reduce the levels and activity of the Yki/YAP
oncogene. Rae1 increases activation of the core kinases Hippo and Warts and plays
a post-transcriptional role to increase the protein levels of the Merlin, Hippo,
and Warts components of the pathway; therefore, in addition to Rae1 coordinating
organ size regulation with proliferative control, we propose that Rae1 also acts
in a feedback circuit to regulate pathway homeostasis.
PMID- 27494405
TI - Estimating Geographical Variation in the Risk of Zoonotic Plasmodium knowlesi
Infection in Countries Eliminating Malaria.
AB - BACKGROUND: Infection by the simian malaria parasite, Plasmodium knowlesi, can
lead to severe and fatal disease in humans, and is the most common cause of
malaria in parts of Malaysia. Despite being a serious public health concern, the
geographical distribution of P. knowlesi malaria risk is poorly understood
because the parasite is often misidentified as one of the human malarias. Human
cases have been confirmed in at least nine Southeast Asian countries, many of
which are making progress towards eliminating the human malarias. Understanding
the geographical distribution of P. knowlesi is important for identifying areas
where malaria transmission will continue after the human malarias have been
eliminated. METHODOLOGY/PRINCIPAL FINDINGS: A total of 439 records of P. knowlesi
infections in humans, macaque reservoir and vector species were collated. To
predict spatial variation in disease risk, a model was fitted using records from
countries where the infection data coverage is high. Predictions were then made
throughout Southeast Asia, including regions where infection data are sparse. The
resulting map predicts areas of high risk for P. knowlesi infection in a number
of countries that are forecast to be malaria-free by 2025 (Malaysia, Cambodia,
Thailand and Vietnam) as well as countries projected to be eliminating malaria
(Myanmar, Laos, Indonesia and the Philippines). CONCLUSIONS/SIGNIFICANCE: We have
produced the first map of P. knowlesi malaria risk, at a fine-scale resolution,
to identify priority areas for surveillance based on regions with sparse data and
high estimated risk. Our map provides an initial evidence base to better
understand the spatial distribution of this disease and its potential wider
contribution to malaria incidence. Considering malaria elimination goals, areas
for prioritised surveillance are identified.
PMID- 27494407
TI - Persistence of focal lymphocytic sialadenitis in patients with primary Sjogren's
syndrome treated with rituximab: a possible role for glandular BAFF.
PMID- 27494408
TI - DNA Methylation Suppresses Leptin Gene in 3T3-L1 Adipocytes.
AB - Leptin is a key regulator of energy intake and expenditure. This peptide hormone
is expressed in mouse white adipose tissue, but hardly expressed in 3T3-L1
adipocytes. Using bisulfite sequencing, we found that CpG islands in the leptin
promoter are highly methylated in 3T3-L1cells. 5-azacytidine, an inhibitor of DNA
methyltransferase, markedly increased leptin expression as pre-adipocytes matured
into adipocytes. Remarkably, leptin expression was stimulated by insulin in
adipocytes derived from precursor cells exposed to 5-azacytidine, but suppressed
by thiazolidinedione and dexamethasone. In contrast, adipocytes derived from
untreated precursor cells were unresponsive to both 5-azacytidine and hormonal
stimuli, although lipid accumulation was sufficient to boost leptin expression in
the absence of demethylation. Taken together, the results suggest that leptin
expression in 3T3-L1 cells requires DNA demethylation prior to adipogenesis,
transcriptional activation during adipogenesis, and lipid accumulation after
adipogenesis.
PMID- 27494409
TI - Is the Karyotype of Neotropical Boid Snakes Really Conserved? Cytotaxonomy,
Chromosomal Rearrangements and Karyotype Organization in the Boidae Family.
AB - Boids are primitive snakes from a basal lineage that is widely distributed in
Neotropical region. Many of these species are both morphologically and
biogeographically divergent, and the relationship among some species remains
uncertain even with evolutionary and phylogenetic studies being proposed for the
group. For a better understanding of the evolutionary relationship between these
snakes, we cytogenetically analysed 7 species and 3 subspecies of Neotropical
snakes from the Boidae family using different chromosomal markers. The karyotypes
of Boa constrictor occidentalis, Corallus hortulanus, Eunectes notaeus, Epicrates
cenchria and Epicrates assisi are presented here for the first time with the
redescriptions of the karyotypes of Boa constrictor constrictor, B. c. amarali,
Eunectes murinus and Epicrates crassus. The three subspecies of Boa, two species
of Eunectes and three species of Epicrates exhibit 2n = 36 chromosomes. In
contrast, C. hortulanus presented a totally different karyotype composition for
the Boidae family, showing 2n = 40 chromosomes with a greater number of
macrochromosomes. Furthermore, chromosomal mapping of telomeric sequences
revealed the presence of interstitial telomeric sites (ITSs) on many chromosomes
in addition to the terminal markings on all chromosomes of all taxa analysed,
with the exception of E. notaeus. Thus, we demonstrate that the karyotypes of
these snakes are not as highly conserved as previously thought. Moreover, we
provide an overview of the current cytotaxonomy of the group.
PMID- 27494411
TI - Adaptive Suspicious Prevention for Defending DoS Attacks in SDN-Based Convergent
Networks.
AB - The convergent communication network will play an important role as a single
platform to unify heterogeneous networks and integrate emerging technologies and
existing legacy networks. Although there have been proposed many feasible
solutions, they could not become convergent frameworks since they mainly focused
on converting functions between various protocols and interfaces in edge
networks, and handling functions for multiple services in core networks, e.g.,
the Multi-protocol Label Switching (MPLS) technique. Software-defined networking
(SDN), on the other hand, is expected to be the ideal future for the convergent
network since it can provide a controllable, dynamic, and cost-effective network.
However, SDN has an original structural vulnerability behind a lot of advantages,
which is the centralized control plane. As the brains of the network, a
controller manages the whole network, which is attractive to attackers. In this
context, we proposes a novel solution called adaptive suspicious prevention (ASP)
mechanism to protect the controller from the Denial of Service (DoS) attacks that
could incapacitate an SDN. The ASP is integrated with OpenFlow protocol to detect
and prevent DoS attacks effectively. Our comprehensive experimental results show
that the ASP enhances the resilience of an SDN network against DoS attacks by up
to 38%.
PMID- 27494410
TI - Resistance Analyses of HCV NS3/4A Protease and NS5B Polymerase from Clinical
Studies of Deleobuvir and Faldaprevir.
AB - BACKGROUND & AIM: The resistance profile of anti-hepatitis C virus (HCV) agents
used in combination is important to guide optimal treatment regimens. We
evaluated baseline and treatment-emergent NS3/4A and NS5B amino-acid variants
among HCV genotype (GT)-1a and -1b-infected patients treated with faldaprevir
(HCV protease inhibitor), deleobuvir (HCV polymerase non-nucleoside inhibitor),
and ribavirin in multiple clinical studies. METHODS: HCV NS3/4A and NS5B
population sequencing (Sanger method) was performed on all baseline plasma
samples (n = 1425 NS3; n = 1556 NS5B) and on post-baseline plasma samples from
patients with virologic failure (n = 113 GT-1a; n = 221 GT-1b). Persistence and
time to loss of resistance-associated variants (RAVs) was estimated using Kaplan
Meier analysis. RESULTS: Faldaprevir RAVs (NS3 R155 and D168) and deleobuvir RAVs
(NS5B 495 and 496) were rare (<1%) at baseline. Virologic response to
faldaprevir/deleobuvir/ribavirin was not compromised by common baseline NS3
polymorphisms (e.g. Q80K in 17.5% of GT-1a) or by NS5B A421V, present in 20% of
GT-1a. In GT-1b, alanine at NS5B codon 499 (present in 15% of baseline sequences)
was associated with reduced response. Treatment-emergent RAVs consolidated
previous findings: NS3 R155 and D168 were key faldaprevir RAVs; NS5B A421 and
P495 were key deleobuvir RAVs. Among on-treatment virologic breakthroughs, RAVs
emerged in both NS3 and NS5B (>90%). Virologic relapse was associated with RAVs
in both NS3 and NS5B (53% GT-1b; 52% GT-1b); some virologic relapses had NS3 RAVs
only (47% GT-1a; 17% GT-1b). Median time to loss of GT-1b NS5B P495 RAVs post
treatment (5 months) was less than that of GT-1b NS3 D168 (8.5 months) and GT-1a
R155 RAVs (11.5 months). CONCLUSION: Faldaprevir and deleobuvir RAVs are more
prevalent among virologic failures than at baseline. Treatment response was not
compromised by common NS3 polymorphisms; however, alanine at NS5B amino acid 499
at baseline (wild-type in GT-1a, polymorphism in GT-1b) may reduce response to
this deleobuvir-based regimen.
PMID- 27494412
TI - Where Do Female Sex Workers Seek HIV and Reproductive Health Care and What
Motivates These Choices? A Survey in 4 Cities in India, Kenya, Mozambique and
South Africa.
AB - BACKGROUND: A baseline cross-sectional survey among female sex workers (FSWs) was
conducted in four cities within the context of an implementation research project
aiming to improve FSWs' access to HIV, and sexual and reproductive health (SRH)
services. The survey measured where FSWs seek HIV/SRH care and what motivates
their choice. METHODS: Using respondent-driven sampling (RDS), FWSs were
recruited in Durban, South Africa (n = 400), Tete, Mozambique (n = 308), Mombasa,
Kenya (n = 400) and Mysore, India (n = 458) and interviewed. RDS-adjusted
proportions were estimated by non-parametric bootstrapping, and compared across
cities using post-hoc pairwise comparison tests. RESULTS: Across cities, FSWs
most commonly sought care for the majority of HIV/SRH services at public health
facilities, most especially in Durban (ranging from 65% for condoms to 97% for
HIV care). Services specifically targeting FSWs only had a high coverage in
Mysore for STI care (89%) and HIV testing (79%). Private-for-profit clinics were
important providers in Mombasa (ranging from 17% for STI care and HIV testing to
43% for HIV care), but not in the other cities. The most important reason for the
choice of care provider in Durban and Mombasa was proximity, in Tete 'where they
always go', and in Mysore cost of care. Where available, clinics specifically
targeting FSWs were more often chosen because of shorter waiting times, perceived
higher quality of care, more privacy and friendlier personnel. CONCLUSION: The
place where care is sought for HIV/SRH services differs substantially between
cities. Targeted services have limited coverage in the African cities compared to
Mysore. Convenience appears more important for choosing the place of care than
aspects of quality of care. The best model to improve access, linking targeted
interventions with general health services, will need to be tailored to the
specific context of each city.
PMID- 27494413
TI - A dual mechanism of cellulose deficiency in shv3svl1.
AB - SHAVEN3 (SHV3) and its homolog SHAVEN3-like 1 (SVL1) encode
glycosylphosphatidylinositol (GPI)-anchored proteins (GAPs) that are involved in
cellulose biosynthesis and hypocotyl elongation in Arabidopsis thaliana. In a
recent report, we showed that the cellulose and hypocotyl elongation defects of
the shv3svl1 double mutant are greatly enhanced by exogenous sucrose in the
growth medium. Further investigation of this phenomenon showed that shv3svl1
exhibits a hyperpolarized plasma membrane (PM) proton gradient that is coupled
with enhanced accumulation of sucrose via the PM sucrose/proton symporter SUC1.
The resulting high intracellular sucrose concentration appears to favor starch
synthesis at the expense of cellulose synthesis. Here, we describe our
interpretation of these results in terms of 2 potential regulators of cellulose
synthesis: intracellular sucrose concentration and a putative signaling pathway
that involves SHV3-like proteins.
PMID- 27494414
TI - Insomnia as a Moderator of Response to Time in Bed Restriction for Augmenting
Antidepressant Treatment: A Preliminary Investigation.
AB - BACKGROUND: There are complex, bidirectional associations between major
depressive disorder and insomnia. In the present study, we evaluated insomnia as
a moderator of response to antidepressant therapy in the context of a sleep
manipulation (time in bed restriction) for major depressive disorder. METHODS:
Fifty-eight adults with major depressive disorder received 8 weeks of fluoxetine
20-40 mgs and were randomized to 8 hr time in bed (8h TIB) or 6 hr time in bed
(6h TIB) for the first 2 weeks (participants in the 6h TIB condition were further
randomized to a delayed bedtime (Late Bedtime) or advanced rise time (Early Rise
Time) group). Insomnia was assessed at baseline using the Insomnia Severity
Index. Depression symptom severity was determined by the clinician-rated 17-item
Hamilton Rating Scale for Depression (HAMD-17), completed weekly. RESULTS: A
group by time interaction was observed whereby HAMD-17 scores were higher for
participants assigned to the 6h TIB group (without insomnia, weeks 3 through 7;
with insomnia from week 3 through 6, ps < .05) relative to participants without
insomnia assigned to the 8h TIB group. There were no differences in HAMD-17
scores for participants with insomnia in the 6h TIB group relative to the 8h TIB
group. CONCLUSION: These preliminary findings suggest that response to fluoxetine
may be hindered by TIB restriction in individuals without insomnia. Individuals
with insomnia respond similarly to fluoxetine regardless of whether their TIB is
restricted. Limitations include exclusive use of self-report measures to
categorize insomnia, and small sample sizes in several of the subgroups.
PMID- 27494415
TI - Simultaneous Identification of 13 Foodborne Pathogens by Using Capillary
Electrophoresis-Single Strand Conformation Polymorphism Coupled with Multiplex
Ligation-Dependent Probe Amplification and Its Application in Foods.
AB - Capillary electrophoresis-single strand conformation polymorphism (CE-SSCP)
coupled with stuffer-free multiplex ligation-dependent probe amplification (MLPA)
was developed to identify 13 species of foodborne pathogens simultaneously.
Species-specific MLPA probes were designed for nine of these species. These
probes were targeted to the groEL, glyA, MMS, tuf, inv, ipaH, nuc, vvh, and 16S
rRNA genes, which corresponded to Bacillus cereus, Campylobacter coli,
Cronobacter sakazakii, Enterococcus spp., Salmonella spp., Shigella spp.,
Staphylococcus aureus, Vibrio vulnificus, and Yersinia enterocolitica,
respectively. MLPA probes that had been previously developed by our laboratory
were used for the other four species (Campylobacter jejuni, Clostridium
perfringens, Escherichia coli O157:H7, and Listeria monocytogenes). The CE-SSCP
method was optimized to identify all 13 foodborne microbes simultaneously in a
single electrogram, in which 50-500 pg genomic DNA was detected per microbe.
Twelve species were detected from animal-derived food samples (specifically, milk
and sliced ham) that had been artificially inoculated with 12 of the foodborne
pathogens, excluding V. vulnificus, which is not usually associated with animal
foods. The method developed here could be used as an early warning system for
outbreaks of foodborne diseases associated with animal-derived foods in the food
industry.
PMID- 27494416
TI - Structural and Thermal Properties of BaTe2O6: Combined Variable-Temperature
Synchrotron X-ray Diffraction, Raman Spectroscopy, and ab Initio Calculations.
AB - Variable-temperature Raman spectroscopic and synchrotron X-ray diffraction
studies were performed on BaTe2O6 (orthorhombic, space group: Cmcm), a mixed
valence tellurium compound with a layered structure, to understand structural
stability and anharmonicity of phonons. The structural and vibrational studies
indicate no phase transition in it over a wider range of temperature (20 to 853
K). The structure shows anisotropic expansion with coefficients of thermal
expansion in the order alphab ? alphaa > alphac, which was attributed to the
anisotropy in bonding and structure of BaTe2O6. Temperature evolution of Raman
modes of BaTe2O6 indicated a smooth decreasing trend in mode frequencies with
increasing temperature, while the full width at half-maximum (fwhm) of all modes
systematically increases due to a rise in phonon scattering processes. With the
use of our earlier reported isothermal mode Gruneisen parameters, thermal
properties such as thermal expansion coefficient and molar specific heat are
calculated. The pure anharmonic (explicit) and quasiharmonic (implicit)
contribution to the total anharmonicity is delineated and compared. The
temperature dependence of phonon mode frequencies and their fwhm values are
analyzed by anharmonicity models, and the dominating anharmonic phonon scattering
mechanism is concluded in BaTe2O6. In addition to the lattice modes, several
external modes of TeOn (n = 5, 6) are found to be strongly anharmonic. The ab
initio electronic structure calculations indicated BaTe2O6 is a direct band gap
semiconductor with gap energy of ~2.1 eV. Oxygen orbitals, namely, O-2p states in
the valence band maximum and the sp-hybridized states in the conduction band
minimum, are mainly involved in the electronic transitions. In addition a number
of electronic transitions are predicted by the electronic structure calculations.
Experimental photoluminescence results are adequately explained by the ab initio
calculations. Further details of the structural and vibrational properties are
explained in the manuscript.
PMID- 27494417
TI - Immunotherapy of advanced renal cell carcinoma: Current and future therapies.
AB - Previously a malignancy with few therapeutic options, metastatic renal cell
carcinoma (mRCC) treatment is rapidly evolving. Although cytokine therapies
(interferon-a, interleukin-2) have been used less frequently over the past
decade, recent approval of an immune checkpoint inhibitor, nivolumab, has led to
a resurgence in immune therapy for mRCC. With greater understanding of the
complex and dynamic interaction between the tumor and the immune system, numerous
new immunotherapies are being studied for mRCC. In this article, we review the
mechanism of action, clinical outcomes and toxicity profiles of both clinically
approved and selected investigational immunotherapies. Either alone or in
combination, these novel agents are encouraging for the future of mRCC therapy.
PMID- 27494418
TI - Diffusion tensor imaging of the inferior alveolar nerve using 3T MRI: a study for
quantitative evaluation and fibre tracking.
AB - OBJECTIVES: Diffusion tensor imaging (DTI) can provide structural information and
objective values for nerves. The aims of this study were to perform quantitative
evaluation and fibre tracking of the normal inferior alveolar nerve (IAN) using
DTI on 3.0-T MRI. METHODS: DTI was applied to 92 IANs of 46 healthy volunteers.
Circular regions of interest (ROIs) were placed on three different positions at
the mandibular foramen, second molar and mental foramen of each nerve on apparent
diffusion coefficient (ADC) and fractional anisotropy (FA) maps, and the ADC and
FA of each ROI were measured. Differences in the values arising from the nerve
positions were evaluated. Furthermore, fibre tracking of the IANs was performed
by tractography, and the quality of visualization was evaluated. RESULTS: There
were no significant differences in the ADC and FA between the right and left
sides regardless of the anteroposterior positions. Regarding differences arising
from the anteroposterior measurement positions, the ADC and FA showed no
significant differences (p > 0.017), except for the ADCs between the positions at
the mandibular foramen and mental foramen in the left side (p = 0.0068). Overall,
70 (76%) of the 92 IANs could be visualized fully or partially by tractography.
CONCLUSIONS: The ADC and FA of the IAN were successfully obtained from healthy
volunteers using DTI and were confirmed to be symmetrical regardless of the
measurement positions. DTI is a feasible technique for the quantitative
evaluation and visualization of the IAN.
PMID- 27494419
TI - The risk of metabolic syndrome in women with previous GDM in a long-term follow
up.
AB - The aim of this study was to evaluate the incidence of metabolic syndrome (MetS)
during long-term follow-up of women with gestational diabetes (GDM). Furthermore,
we evaluated the glycemic measures from an oral glucose tolerance test (OGTT)
during pregnancy as predictors of incident MetS. Women diagnosed with GDM were
divided into two groups according to the results of OGTT: one abnormal value =
GDM1 (n = 338) and two abnormal values = GDM2 (n = 151), while women with normal
glucose tolerance (n = 385) served as controls. MetS and its components were
evaluated in a follow-up study (mean follow-up time 7.3 +/- 5.1 years) according
to the International Diabetes Federation (IDF) criteria. Fasting plasma glucose
in OGTT was the best predictor of incident MetS in ROC (area under the curve)
analysis. The incidence of MetS during a <5-year follow-up was 22.2% in controls,
39.3% in GDM1 and 60.4% in GDM2; and >10-year follow-up 24.2%, 46.2% and 62.5%,
respectively. In controls and GDM2, the incidence of MetS remained nearly
constant during the follow-up, whereas in GDM1 it increased. In conclusion,
already mild gestational glucose intolerance may progress to MetS and therefore
merits intervention measures to prevent future cardiovascular disease.
PMID- 27494420
TI - In vitro and in vivo investigation of taste-masking effectiveness of Eudragit E
PO as drug particle coating agent in orally disintegrating tablets.
AB - CONTEXT: Considering that bitter taste of drugs incorporated in orally
disintegrating tablets (ODTs) can be the main reason for avoiding drug therapy,
it is of the utmost importance to achieve successful taste-masking. The
evaluation of taste-masking effectiveness is still a major challenge. OBJECTIVE:
The objective of this study was to mask bitter taste of the selected model drugs
by drug particle coating with Eudragit(r) E PO, as well as to evaluate taste
masking effectiveness of prepared ODTs using compendial dissolution testing,
dissolution in the small-volume shake-flask assembly and trained human taste
panel. MATERIALS AND METHODS: Model drugs were coated in fluidized bed.
DisintequikTM ODT was used as a novel co-processed excipient for ODT preparation.
Selected formulations were investigated in vitro and in vivo using techniques for
taste-masking assessment. RESULTS AND DISCUSSION: Significantly slower drug
dissolution was observed from tablets with coated drug particles during the first
3 min of investigation. Results of in vivo taste-masking assessment demonstrated
significant improvement in drug bitterness suppression in formulations with
coated drug. Strong correlation between the results of drug dissolution in the
small-volume shake-flask assembly and in vivo evaluation data was established (R
>= 0.970). CONCLUSION: Drug particle coating with Eudragit(r) E PO can be a
suitable approach for bitter taste-masking. Strong correlation between in vivo
and in vitro results implicate that small-volume dissolution method may be used
as surrogate for human panel taste-masking assessment, in the case of physical
taste-masking approach application.
PMID- 27494421
TI - The O-antigen of Plesiomonas shigelloides serotype O36 containing pseudaminic
acid.
AB - The structure of the repeating unit of O-antigen of Plesiomonas shigelloides
serotype O36 has been investigated by 1H and 13C NMR spectroscopy, matrix
assisted laser-desorption/ionization time-of-flight mass spectrometry and
chemical methods. The new structure of trisaccharide has been established:
[Formula: see text] These trisaccharide O-antigen units substitute the core
undecasaccharide at C-4 of the beta-D-GlcpNAc residue. The core oligosaccharide
and lipid A are identical with these of the serotype O17 (PCM 2231) (Maciejewska,
A., Lukasiewicz, J., Kaszowska, M., Jachymek, W., Man-Kupisinska, A.; Lugowski,
C. Mar. Drugs.2013, 11 (2), 440-454; Lukasiewicz, J., Dzieciatkowska, M.,
Niedziela, T., Jachymek, W., Augustyniuk, A., Kenne, L., Lugowski, C.
Biochemistry, 2006, 45, 10434-10447).
PMID- 27494422
TI - Large volume sample stacking of cationic tetracycline antibiotics toward 10 ppb
level analysis by capillary electrophoresis with UV detection.
AB - This paper aimed to build up a sensitive CE method for the analysis of
tetracyclines (TCs) antibiotics (including tetracycline, chlorotetracycline,
oxytetracycline, and doxycycline) with conventional UV detection. Here, the large
volume sample stacking was applied to achieve in capillary preconcentration of
the targets. To achieve large volume sample stacking, the essential step was a
large volume of sample (around 83.3% of total capillary length from inlet to
detection window) hydrodynamically loaded. Then, the reserved voltage was added
in order to push the sample matrix out of the capillary. Due to different pH
between sample solution (pH 4.6) and BGE (pH 11.0), the cationic TCs would turn
into negatively charged while the sample matrix was removing from the capillary.
Finally, the anionic TCs were stacked at the inlet for the subsequent separation.
Although the loss of sample existed during their charge transformation, the LODs
could be improved around 40 times than that obtained by normal hydrodynamic
injection CE method. Here, the LODs were in the range of 8.1-14.5 MUg/L, around
10 ppb that close to the level by electrochemiluminescence or laser-induced
fluorescence detection of TCs by CE. The precision was characterized by RSDs of
migration times and peak areas, which were in the range of 0.19-0.24% and 0.97
2.54%, respectively. The recoveries of the developed method were in the range of
95-112% by spiking TCs in the tap water. The proposed inline preconcentration CE
method could be a simple, speed, and sensitive method for the quantitative
analysis of TCs.
PMID- 27494423
TI - Self-limiting multiplexed assembly of lipid membranes on large-area graphene
sensor arrays.
AB - Phospholipid membranes of different functionalities were simultaneously assembled
on arrays of graphene surfaces in a parallel manner using multi-pen lipid dip-pen
nano-lithography. The graphene patch facilitates and restricts the spreading of
lipids within itself, obviating the need to scan the writing probes and reducing
writing time. Binding studies establish that the lipids retain the functionality.
PMID- 27494424
TI - Effects of Environmental pH on Antioxidant Interactions between Rosmarinic Acid
and alpha-Tocopherol in Oil-in-Water (O/W) Emulsions.
AB - Antioxidant regeneration could be influenced by various factors such as
antioxidant locations and pH conditions. The effects of environmental pH on the
antioxidant interaction between rosmarinic acid and alpha-tocopherol in oil-in
water (O/W) emulsions were investigated. Results showed that the combined
antioxidants at pH 7 exhibited the strongest synergistic antioxidant activity in
comparison with the combinations at other pH conditions as indicated by the
interaction index. A drop in pH from 7 to 3 resulted in a reduction in the
synergistic effect. However, in the case of pH 3, an additive effect was
obtained. Moreover, the effect of the pH on the regeneration of alpha-tocopherol
by rosmarinic acid in heterogeneous Tween 20 solutions was studied using EPR
spectrometer. The same was true for the regeneration efficiency, where the
reaction at pH 7 exhibited the highest regeneration efficiency of 0.3 mol of
alpha-tocopheroxyl radicals reduced/mol of phenolics. However, the study on
depletions of rosmarinic acid and alpha-tocopherol revealed that the formation of
caffeic acid, an oxidative degradation product of rosmarinic acid, could be
involved in enhancing the antioxidant activity observed at pH 7 rather than the
antioxidant regeneration. This study has highlighted that the importance of pH
dependent antioxidant interactions does not solely rely on antioxidant
regeneration. In addition, the formation of other oxidative products from an
antioxidant should be taken into account.
PMID- 27494425
TI - La/Sm/Er Cation Doping Induced Thermal Properties of SrTiO3 Perovskite.
AB - The La/Sm/Er cations with different radii doping SrTiO3 (STO) as model
Sr0.9R0.1TiO3 (R = La, Sm, Er) were designed to investigate structural
characteristics and thermal properties by the molecular dynamics simulation with
the Green-Kubo relation at 300-2000 K. The structural characteristics were
composed of lattice constant, atoms excursion, and pair correlation function
(PCF). The thermal properties consisted of heat capacity and thermal
conductivity. The lattice constant of R-doped exhibited less than the STO at 300
1100 K and more than STO at 1500-2000 K, which was encouraged by atom excursion
and PCF. The thermal properties was compared with literature data at 300-1100 K.
In addition, the thermal properties at 1100-2000 K were predicted. It highlights
that thermal conductivity tends to decrease at high temperature, due to
perturbation of La, Sm, and Er, respectively.
PMID- 27494426
TI - High Piezo-photocatalytic Efficiency of CuS/ZnO Nanowires Using Both Solar and
Mechanical Energy for Degrading Organic Dye.
AB - High piezo-photocatalytic efficiency of degrading organic pollutants has been
realized from CuS/ZnO nanowires using both solar and mechanical energy. CuS/ZnO
heterostructured nanowire arrays are compactly/vertically aligned on stainless
steel mesh by a simple two-step wet-chemical method. The mesh-supported
nanocomposites can facilitate an efficient light harvesting due to the large
surface area and can also be easily removed from the treated solution. Under both
solar and ultrasonic irradiation, CuS/ZnO nanowires can rapidly degrade methylene
blue (MB) in aqueous solution, and the recyclability is investigated. In this
process, the ultrasonic assistance can greatly enhance the photocatalytic
activity. Such a performance can be attributed to the coupling of the built-in
electric field of heterostructures and the piezoelectric field of ZnO nanowires.
The built-in electric field of the heterostructure can effectively separate the
photogenerated electrons/holes and facilitate the carrier transportation. The CuS
component can improve the visible light utilization. The piezoelectric field
created by ZnO nanowires can further separate the photogenerated electrons/holes
through driving them to migrate along opposite directions. The present results
demonstrate a new water-pollution solution in green technologies for the
environmental remediation at the industrial level.
PMID- 27494427
TI - Biopreservation and Biobanking Mid-Year Report.
PMID- 27494429
TI - Interventions for compassionate nursing care: A systematic review.
AB - BACKGROUND: Compassion has been identified as an essential element of nursing and
is increasingly under public scrutiny in the context of demands for high quality
health care. While primary research on effectiveness of interventions to support
compassionate nursing care has been reported, no rigorous critical overview
exists. OBJECTIVES: To systematically identify, describe and analyse research
studies that evaluate interventions for compassionate nursing care; assess the
descriptions of the interventions for compassionate care, including design and
delivery of the intervention and theoretical framework; and to evaluate evidence
for the effectiveness of interventions. REVIEW METHODS: Published international
literature written in English up to June 2015 was identified from CINAHL, Medline
and Cochrane Library databases. Primary research studies comparing outcomes of
interventions to promote compassionate nursing care with a control condition were
included. Studies were graded according to relative strength of methods and
quality of description of intervention. Narrative description and analysis was
undertaken supported by tabulation of key study data including study design,
outcomes, intervention type and results. RESULTS: 25 interventions reported in 24
studies were included in the review. Intervention types included staff training
(n=10), care model (n=9) and staff support (n=6). Intervention description was
generally weak, especially in relation to describing participants and
facilitators, and the proposed mechanisms for change were often unclear. Most
interventions were associated with improvements in patient-based, nurse-based
and/or quality of care outcomes. However, overall methodological quality was low
with most studies (n=16) conducted as uncontrolled before and after studies. The
few higher quality studies were less likely to report positive results. No
interventions were tested more than once. CONCLUSIONS: None of the studies
reviewed reported intervention description in sufficient detail or presented
sufficiently strong evidence of effectiveness to merit routine implementation of
any of these interventions into practice. The positive outcomes reported suggest
that further investigation of some interventions may be merited, but high caution
must be exercised. Preference should be shown for further investigating
interventions reported as effective in studies with a stronger design such as
randomised controlled trials.
PMID- 27494428
TI - Enroling and retaining human immunodeficiency virus (HIV) patients in their care:
A metasynthesis of qualitative studies.
AB - OBJECTIVES: To report the findings of a metasynthesis review of qualitative
studies on patient and provider experiences and perspectives on linkage and
retention in HIV care. DESIGN: The review is an extraction, aggregation,
interpretation and synthesis of qualitative findings based on the Sandelowski and
Barroso method. DATA SOURCES: A search of the literature was conducted in the
databases Cumulative Index to Nursing and Allied Health, PubMed and PsycInfo for
articles published from 2008 to 2013. Inclusion criteria were qualitative
research articles published in English from across the world and in peer-reviewed
journals. Literature reviews, conference abstracts and grey literature were
excluded from this metasynthesis. REVIEW METHODS: The review consisted of a)
comprehensive search, b) study classification, c) abstraction of findings, d)
synthesis. Of the 4640 citations screened, 69 articles were included for this
metasynthesis. RESULTS: 69 unique articles from 44 countries were included. This
metasynthesis takes into account the perspectives of at least 2263 HIV-positive
participants (740 men, 1008 women, 78 transgender individuals and 437 unspecified
sex) and 994 healthcare providers, family members and community members. The most
salient barriers and facilitators to HIV linkage and retention in HIV care affirm
ecological factors that are mostly beyond individual patients' control. Triadic
streams of influence concurrently affect care engagement that include a person's
psychological state upon diagnosis and their informational challenges
(intrapersonal stream); one-on-one interactions with providers and their
immediate community (social stream); and life demands, overall quality of care
experiences and other structural barriers (cultural-attitudinal stream). Each
stream's influence on HIV care engagement varies at any given point to reflect an
individual's evolving and unique experiences with HIV infection throughout the
illness trajectory. CONCLUSION: There is sufficient evidence that detail how to
best link and retain patients in HIV care. Themes identified indicate going
beyond individual-level factors and towards shifting attention and resources to
systems that patients navigate. Forceful structural-level actions are needed to
correct these long-identified barriers and enhance care engagement facilitators.
PMID- 27494430
TI - Nurse practitioner caseload in primary health care: Scoping review.
AB - OBJECTIVES: To identify recommendations for determining patient panel/caseload
size for nurse practitioners in community-based primary health care settings.
DESIGN: Scoping review of the international published and grey literature. DATA
SOURCES: The search included electronic databases, international professional and
governmental websites, contact with experts, and hand searches of reference
lists. Eligible papers had to (a) address caseload or patient panels for nurse
practitioners in community-based primary health care settings serving an all-ages
population; and (b) be published in English or French between January 2000 and
July 2014. Level one testing included title and abstract screening by two team
members. Relevant papers were retained for full text review in level two testing,
and reviewed by two team members. A third reviewer acted as a tiebreaker. Data
were extracted using a structured extraction form by one team member and verified
by a second member. Descriptive statistics were estimated. Content analysis was
used for qualitative data. RESULTS: We identified 111 peer-reviewed articles and
grey literature documents. Most of the papers were published in Canada and the
United States after 2010. Current methods to determine panel/caseload size use
large administrative databases, provider work hours and the average number of
patient visits. Most of the papers addressing the topic of patient panel/caseload
size in community-based primary health care were descriptive. The average number
of patients seen by nurse practitioners per day varied considerably within and
between countries; an average of 9-15 patients per day was common. Patient
characteristics (e.g., age, gender) and health conditions (e.g., multiple chronic
conditions) appear to influence patient panel/caseload size. Very few studies
used validated tools to classify patient acuity levels or disease burden scores.
DISCUSSION: The measurement of productivity and the determination of
panel/caseload size is complex. Current metrics may not capture activities
relevant to community-based primary health care nurse practitioners. Tools to
measure all the components of these role are needed when determining
panel/caseload size. Outcomes research is absent in the determination of
panel/caseload size. CONCLUSION: There are few systems in place to track and
measure community-based primary health care nurse practitioner activities. The
development of such mechanisms is an important next step to assess community
based primary health care nurse practitioner productivity and determine patient
panel/caseload size. Decisions about panel/caseload size must take into account
the effects of nurse practitioner activities on outcomes of care.
PMID- 27494431
TI - Selectivity Determination of a Small Molecule Chemical Probe Using Protein
Microarray and Affinity Capture Techniques.
AB - Small molecule selectivity is an essential component of candidate drug selection
and target validation. New technologies are required to better understand off
target effects, with particular emphasis needed on broad protein profiling. Here,
we describe the use of a tritiated chemical probe and a 9000 human protein
microarray to discern the binding selectivity of an inhibitor of the mRNA
decapping scavenger enzyme DcpS. An immobilized m7GTP resin was also used to
assess the selectivity of a DcpS inhibitor against mRNA cap-associated proteins
in whole cell extracts. These studies confirm the exquisite selectivity of
diaminoquinazoline DcpS inhibitors, and highlight the utility of relatively
simple protein microarray and affinity enrichment technologies in drug discovery
and chemical biology.
PMID- 27494432
TI - Gelatin Methacrylate Hydrogels as Biomimetic Three-Dimensional Matrixes for
Modeling Breast Cancer Invasion and Chemoresponse in Vitro.
AB - Recent studies have shown that three-dimensional (3D) culture environments allow
the study of cellular responses in a setting that more closely resembles the in
vivo milieu. In this context, hydrogels have become popular scaffold options for
the 3D cell culture. Because the mechanical and biochemical properties of culture
matrixes influence crucial cell behavior, selecting a suitable matrix for
replicating in vivo cellular phenotype in vitro is essential for understanding
disease progression. Gelatin methacrylate (GelMA) hydrogels have been the focus
of much attention because of their inherent bioactivity, favorable hydration and
diffusion properties, and ease-of-tailoring of their physicochemical
characteristics. Therefore, in this study we examined the efficacy of GelMA
hydrogels as a suitable platform to model specific attributes of breast cancer.
We observed increased invasiveness in vitro and increased tumorigenic ability in
vivo in breast cancer cells cultured on GelMA hydrogels. Further, cells cultured
on GelMA matrixes were more resistant to paclitaxel treatment, as shown by the
results of cell-cycle analysis and gene expression. This study, therefore,
validates GelMA hydrogels as inexpensive, cell-responsive 3D platforms for
modeling key characteristics associated with breast cancer metastasis, in vitro.
PMID- 27494433
TI - Directed Assembly of Nanoparticle Catalysts on Nanowire Photoelectrodes for
Photoelectrochemical CO2 Reduction.
AB - Reducing carbon dioxide with a multicomponent artificial photosynthetic system,
closely mimicking nature, represents a promising approach for energy storage.
Previous works have focused on exploiting light-harvesting semiconductor
nanowires (NW) for photoelectrochemical water splitting. With the newly developed
CO2 reduction nanoparticle (NP) catalysts, direct interfacing of these
nanocatalysts with NW light absorbers for photoelectrochemical reduction of CO2
becomes feasible. Here, we demonstrate a directed assembly of NP catalysts on
vertical NW substrates for CO2-to-CO conversion under illumination. Guided by the
one-dimensional geometry, well-dispersed assembly of Au3Cu NPs on the surface of
Si NW arrays was achieved with facile coverage tunability. Such Au3Cu NP
decorated Si NW arrays can readily serve as effective CO2 reduction
photoelectrodes, exhibiting high CO2-to-CO selectivity close to 80% at -0.20 V vs
RHE with suppressed hydrogen evolution. A reduction of 120 mV overpotential
compared to the planar (PL) counterpart was observed resulting from the optimized
spatial arrangement of NP catalysts on the high surface area NW arrays. In
addition, this system showed consistent photoelectrochemical CO2 reduction
capability up to 18 h. This simple photoelectrode assembly process will lead to
further progress in artificial photosynthesis, by allowing the combination of
developments in each subfield to create an efficient light-driven system
generating carbon-based fuels.
PMID- 27494434
TI - Novel organelles in primate retinal epithelium.
AB - We are investigating age-related changes in organelles in monkey retinal
epithelium using transmission and analytic electron microscopy. We previously
described a circular organelle in retinal epithelium with a diameter of about
0.5MUm. The organelle is unique in containing a single, round vacuole within an
otherwise electron dense interior. We suggested that the organelle might be a
melanosome with lysosomal properties. We now find that there are two similar
organelles with such a single vacuole but which differ in their chemical
composition, electron density, cell location and according to age. Epon embedded
sections from the macular epithelium of seven monkeys, ranging from 1 to 35 years
of age, were examined by transmission electron microscopy. A seven year old
monkey was processed for analytic electron microscopy to determine the chemical
composition of the organelles. The number and location of the organelles in the
retinal epithelium were determined. The chemical composition of these two
organelles was different. One of the organelles contained high mole fractions of
oxygen and nitrogen and little phosphorous characteristic of melanin; the other
had little oxygen and nitrogen and higher mole fractions of phosphorous
uncharacteristic of melanin, but more common with lysosomal organelles. The
latter had an electron dense rim around the vacuole, a less electron dense
interior than the melanin containing organelle and also contained iron. The
melanin containing organelle was more common in young monkeys and in the middle
third of the cell. The organelle without melanin was more common in old monkeys
and localized in the basal third of the cell. Two similarly vacuolated
organelles, not identified before in retinal epithelium, differ in their chemical
composition. One contains melanin; the other does not. The former is more common
in young and the latter more common in old monkeys. This suggests reorganization
and or degradation of melanin-containing organelles with age. These changes show
how analytic electron microscopy can distinguish major ultra-structural
differences in organelles when mere observation fails to do so easily.
PMID- 27494435
TI - Adult Intraosseous Access by Advanced EMTs: A Statewide Non-Inferiority Study.
AB - OBJECTIVE: Intraosseous (IO) access is increasingly being used as an alternative
to peripheral intravenous access, which is often difficult or impossible to
establish in critically ill patients in the prehospital setting. Until recently,
only Paramedics performed adult IO access. In 2014, Vermont Emergency Medical
Services (EMS) expanded the Advanced Emergency Medical Technicians (AEMTs) scope
of practice to include IO access in adult patients. This study compares
successful IO access in adults performed by AEMTs compared to Paramedics in the
prehospital setting. METHODS: All Vermont EMS patient encounters between January
1, 2013 and November 30, 2015 were examined, and 543 adult patients with a
documented IO access insertion attempt were identified. The proportion of
successful IO insertions was compared between AEMTs and Paramedics using a Chi
Squared statistic and a non-inferiority test. RESULTS: There was no significant
difference in the percentage of successful IO access between AEMTs and Paramedics
[95.2% and 95.6%, respectively; P = 0.84]. The confidence interval around this
0.4% difference (95% confidence interval = -4.2, 3.2) was within a pre-specified
delta of +/-10% indicating non-inferiority of AEMTs compared to Paramedics.
CONCLUSIONS: This study's finding that successful IO access was not different
among AEMTs and Paramedics lends evidence in support of expanding the scope of
practice of AEMTs to include establishing IO access in adults.
PMID- 27494436
TI - The co-occurrence of nicotine and other substance use and addiction among youth
and adults in the United States: implications for research, practice, and policy.
AB - BACKGROUND: The increasing popularity of non-cigarette nicotine products,
especially among youth, highlights the need for greater attention to their
potential risks, including nicotine addiction and other substance use and
addiction. OBJECTIVES: To examine the extent to which nicotine product use co
occurs with other substance use and addiction among youth and adults, describe
the demographic groups and types of nicotine products associated with an
increased risk of such co-occurrence, and discuss implications for research,
prevention, clinical practice, and policy. METHODS: Analyzing 2014 data from two
nationally representative US surveys, the National Survey on Drug Use and Health
(NSDUH) and the Monitoring the Future (MTF) study, we examined the co-occurrence
between nicotine product use and alcohol and other drug use and addiction.
RESULTS: Individuals of all ages who reported using nicotine products of any kind
were significantly more likely than nonusers to report alcohol, marijuana, other
drug, and poly-substance use and to meet diagnostic criteria for a substance-use
disorder. Users of multiple nicotine products generally were the most likely to
engage in alcohol and other drug use and to be addicted to these other
substances. CONCLUSIONS: The substantial co-occurrence of all forms of nicotine
use and other substance use and addiction underscores the need to control the
growing use of non-cigarette nicotine products among youth and to incorporate all
forms of nicotine product use into substance use and addiction research,
prevention, clinical practice, and policy efforts.
PMID- 27494437
TI - Antimicrobial Cluster Bombs: Silver Nanoclusters Packed with Daptomycin.
AB - Integration of two distinctive bactericides into one entity is a promising
platform to improve the efficiency of antimicrobial agents. We report an
efficient antimicrobial hybrid formed through conjugating silver nanoclusters
(AgNCs) with daptomycin. The as-designed antimicrobial hybrid (D-AgNCs) inherits
intrinsic properties of both bactericides with an enhanced synergistic
performance. In particular, the chemically integrated D-AgNCs showed improved
bacterial killing efficiency over the physically mixed daptomycin and AgNCs
(D+AgNCs). More interestingly, the as-designed D-AgNCs could effectively damage
the bacterial membrane. Propidium iodide (PI) stain showed bacterial membrane
damage in about 85% of the bacteria population after treatment with D-AgNCs
through creation of larger pores on the membrane as compared to D+AgNCs, largely
due to the localization of daptomycin within the hybrid structure. These larger
pores facilitated the entry of the D-AgNCs into the cell and led to more severe
DNA damage of the bacterial DNA as compared to D+AgNCs in genomic DNA PAGE
analysis. TUNEL assay further depicted more bacterial DNA breaks induced by D
AgNCs. The RecA gene expression level was upregulated, suggestive of DNA repair
activation. The strong induced DNA damage benefited from the localization of
AgNCs in the core of the antimicrobial hybrid structure, which could generate
localized high ROS concentration and work as a critical ROS reservoir to
continually generate ROS within the bacterium. The continual bombardments by
these ROS generators restrict the ability of the bacteria to now develop
resistance against this.
PMID- 27494438
TI - Pair Potential That Reproduces the Shape of Isochrones in Molecular Liquids.
AB - Many liquids have curves (isomorphs) in their phase diagrams along which
structure, dynamics, and some thermodynamic quantities are invariant in reduced
units. A substantial part of their phase diagrams is thus effectively one
dimensional. The shapes of these isomorphs are described by a material-dependent
function of density, h(rho), which for real liquids is well approximated by a
power law, rho(gamma). However, in simulations, a power law is not adequate when
density changes are large; typical models, such as Lennard-Jones liquids, show
that gamma(rho) = d ln h(rho)/d ln rho is a decreasing function of density. This
article presents results from computer simulations using a new pair potential
that diverges at a nonzero distance and can be tuned to give a more realistic
shape of gamma(rho). Our results indicate that the finite size of molecules is an
important factor to take into account when modeling liquids over a large density
range.
PMID- 27494439
TI - Mindful Connections: The Role of a Peer Support Group on the Psychosocial
Adjustment for Adults Recovering From Brain Injury.
AB - How does participating in a peer support group impact an adult's psychosocial
adjustment following brain injury? This question was investigated using a
qualitative approach, interviewing patients recruited from an ambulatory care
program. Data analysis guided by Bury's sociological framework, biographical
disruption and biographical repair, revealed participants' pregroup disrupted
sense of self, including subthemes related to intrinsic losses and uncertainty.
Enhanced psychosocial adjustment including subthemes described participants'
reorientation through shared experience. Finally, a postgroup adapted sense of
self including subthemes was characterized by heightened purpose, self-awareness,
and acceptance. Findings lend weight to using tailored peer interventions to
optimize psychosocial adjustment for this population.
PMID- 27494440
TI - Microalgae-activated sludge treatment of molasses wastewater in sequencing batch
photo-bioreactor.
AB - The aim of this work was the examination of the treatment potential of molasses
wastewater, by the utilization of activated sludge and microalgae. The systems
used included a sequencing batch bioreactor and a similar photo-bioreactor,
favoring microalgae growth. The microalgae treatment of molasses wastewater
mixture resulted in a considerable reduction in the total nitrogen content. A
reduction in the ammonium and nitrate content was observed in the photo
bioreactor, while the effluent's total nitrogen consisted mainly of 50% organic
nitrogen. The transformation of the nitrogen forms in the photo-bioreactor was
attributed to microalgae activity, resulting in the production of a better
quality effluent. Lower COD removal was observed for the photo-bioreactor than
the control, which however increased, by the replacement of the anoxic phase by a
long aeration period. The mechanism of nitrogen removal included both the
denitrification process during the anoxic stage and the microalgae activities, as
the replacement of the anoxic stage resulted in low total nitrogen removal
capacities. A decrease in the photobioreactor performance was observed after 35
days of operation due to biofilm formation on the light tube surface, while the
operation at higher temperature accelerated microalgae growth, resulting thus in
the early failure of the photoreactor.
PMID- 27494441
TI - Sparsity-constrained PET image reconstruction with learned dictionaries.
AB - PET imaging plays an important role in scientific and clinical measurement of
biochemical and physiological processes. Model-based PET image reconstruction
such as the iterative expectation maximization algorithm seeking the maximum
likelihood solution leads to increased noise. The maximum a posteriori (MAP)
estimate removes divergence at higher iterations. However, a conventional
smoothing prior or a total-variation (TV) prior in a MAP reconstruction algorithm
causes over smoothing or blocky artifacts in the reconstructed images. We propose
to use dictionary learning (DL) based sparse signal representation in the
formation of the prior for MAP PET image reconstruction. The dictionary to
sparsify the PET images in the reconstruction process is learned from various
training images including the corresponding MR structural image and a self
created hollow sphere. Using simulated and patient brain PET data with
corresponding MR images, we study the performance of the DL-MAP algorithm and
compare it quantitatively with a conventional MAP algorithm, a TV-MAP algorithm,
and a patch-based algorithm. The DL-MAP algorithm achieves improved bias and
contrast (or regional mean values) at comparable noise to what the other MAP
algorithms acquire. The dictionary learned from the hollow sphere leads to
similar results as the dictionary learned from the corresponding MR image.
Achieving robust performance in various noise-level simulation and patient
studies, the DL-MAP algorithm with a general dictionary demonstrates its
potential in quantitative PET imaging.
PMID- 27494443
TI - Letter to the Editor: RNF213 variant and quasimoyamoya disease.
PMID- 27494442
TI - Perinatal Exposure to Traffic-Related Air Pollution and Autism Spectrum
Disorders.
AB - BACKGROUND: Studies from the United States indicate that exposure to air
pollution in early life is associated with autism spectrum disorders (ASD) in
children, but the evidence is not consistent with European data. OBJECTIVE: We
aimed to investigate the association between exposure to air pollution from road
traffic and the risk of ASD in children, with careful adjustment for
socioeconomic and other confounders. METHOD: Children born and residing in
Stockholm, Sweden, during 1993-2007 with an ASD diagnosis were identified through
multiple health registers and classified as cases (n = 5,136). A randomly
selected sample of 18,237 children from the same study base constituted controls.
Levels of nitrogen oxides (NOx) and particulate matter with diameter <= 10 MUm
(PM10) from road traffic were estimated at residential addresses during mother's
pregnancy and the child's first year of life by dispersion models. Odds ratios
(OR) and 95% confidence intervals (CI) for ASD with or without intellectual
disability (ID) were estimated using logistic regression models after
conditioning on municipality and calendar year of birth as well as adjustment for
potential confounders. RESULT: Air pollution exposure during the prenatal period
was not associated with ASD overall (OR = 1.00; 95% CI: 0.86, 1.15 per 10-MUg/m3
increase in PM10 and OR = 1.02; 95% CI: 0.94, 1.10 per 20-MUg/m3 increase in NOx
during mother's pregnancy). Similar results were seen for exposure during the
first year of life, and for ASD in combination with ID. An inverse association
between air pollution exposure and ASD risk was observed among children of
mothers who moved to a new residence during pregnancy. CONCLUSION: Early-life
exposure to low levels of NOx and PM10 from road traffic does not appear to
increase the risk of ASD. Citation: Gong T, Dalman C, Wicks S, Dal H, Magnusson
C, Lundholm C, Almqvist C, Pershagen G. 2017. Perinatal exposure to traffic
related air pollution and autism spectrum disorders. Environ Health Perspect
125:119-126; http://dx.doi.org/10.1289/EHP118.
PMID- 27494444
TI - Prevalence of potential familial hypercholesteremia (FH) in 54,811 statin-treated
patients in clinical practice.
AB - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a life-threatening
disease, characterized by elevated LDL-C levels and a premature, increased risk
of coronary heart disease (CHD) that is globally underdiagnosed. The percentage
of patients with possible or probable FH in various countries was examined in the
Dyslipidemia International Study (DYSIS). METHODS: DYSIS is a multinational,
cross-sectional observational study of 54,811 adult outpatients treated with
statin therapy. The percentages of patients with high levels of LDL-C, and with
possible or probable FH, were assessed using the Dutch scoring method for FH
across 29 countries, in age subgroups for the analysis population and among
diabetes patients. RESULTS: Despite statin therapy, 16.1% (range 4.4-27.6%) of
patients had LDL-C >3.6 mmol/L (140 mg/dL) across countries and the prevalence of
possible FH was 15.0% (range 5.5-27.8%) and 1.1% (range 0.0-5.4%) for probable
FH. The highest percentages of probable FH occurred in Egypt (5.4%), the Baltic
states (4.2%), Russia (3.2%), and Slovenia (3.1%), with the lowest rates in
Israel (0.0%), Canada (0.2%), and Sweden (0.3%). Rates of FH were the highest in
younger patients (45-54 years) for secondary prevention, regardless of the
presence/absence of diabetes. CONCLUSIONS: Despite statin therapy, high LDL-C
levels and rates of possible and probable FH were observed in some countries. The
prevalence of FH was the highest in younger age patients, and >60% of patients
with probable FH displayed CHD. Earlier diagnosis and treatment of patients with
FH are needed to reduce CHD risk in these patients.
PMID- 27494445
TI - Atherosclerotic plaque behind the stent changes after bare-metal and drug-eluting
stent implantation in humans: Implications for late stent failure?
AB - BACKGROUND AND AIMS: The natural history and the role of atherosclerotic plaque
located behind the stent (PBS) are still poorly understood. We evaluated the
serial changes in PBS following bare-metal (BMS) compared to first-generation
drug-eluting stent (DES) implantation and the impact of these changes on in-stent
neointimal hyperplasia (NIH). METHODS: Three-dimensional coronary reconstruction
by angiography and intravascular ultrasound was performed after intervention and
at 6-10-month follow-up in 157 patients with 188 lesions treated with BMS (n =
89) and DES (n = 99). RESULTS: There was a significant decrease in PBS area (
7.2%; p < 0.001) and vessel area (-1.7%; p < 0.001) after BMS and a respective
increase in both areas after DES implantation (6.1%; p < 0.001 and 4.1%; p <
0.001, respectively). The decrease in PBS area significantly predicted neointimal
area at follow-up after BMS (beta: 0.15; 95% confidence interval [CI]: 0.10-0.20,
p < 0.001) and DES (beta: 0.09; 95% CI: 0.07-0.11; p < 0.001) implantation. The
decrease in PBS area was the most powerful predictor of significant NIH after BMS
implantation (odds ratio: 1.13; 95% CI: 1.02-1.26; p = 0.02). CONCLUSIONS: The
decrease in PBS area after stent implantation is significantly associated with
the magnitude of NIH development at follow-up. This finding raises the
possibility of a communication between the lesion within the stent and the
underlying native atherosclerotic plaque, and may have important implications
regarding the pathobiology of in-stent restenosis and late/very late stent
thrombosis.
PMID- 27494446
TI - The relationship between vitamin K and peripheral arterial disease.
AB - BACKGROUND AND AIMS: A high dietary intake of vitamin K1 (phylloquinone) and
vitamin K2 (menaquinones) is thought to decrease cardiovascular disease risk by
reducing vascular calcification. The objective of this study is to explore if
there is a relationship between phylloquinone and menaquinones intake and risk of
PAD. METHODS: We investigated the association between intake of phylloquinone and
menaquinones with PAD in a prospective cohort with 36,629 participants.
Occurrence of PAD was obtained by linkage to national registries. Baseline intake
of phylloquinone and menaquinones was estimated using a validated food-frequency
questionnaire. Multivariate Cox regression was used to estimate adjusted hazard
ratio's for the association. RESULTS: During 12.1 years (standard deviation 2.1
years) of follow-up, 489 incident cases of PAD were documented. Menaquinones
intake was associated with a reduced risk of PAD with a hazard ratio (HR) of
0.71, 95% CI; 0.53-0.95 for the highest versus lowest quartile. A stronger
association was observed (p interaction 0.0001) in participants with hypertension
(HRQ4 versus Q1 0.59; 95% CI 0.39-0.87) or diabetes (HRQ4 versus Q1 0.56; 95% CI
0.18-1.91), though confidence intervals were wide in the small (n = 530) diabetes
stratum. Phylloquinone intake was not associated with PAD risk. CONCLUSIONS: High
intake of menaquinones was associated with a reduced risk of PAD, at least in
hypertensive participants. High intake of phylloquinone was not associated with a
reduced risk of PAD.
PMID- 27494447
TI - Dietary counseling is associated with an improved lipid profile in children with
familial hypercholesterolemia.
AB - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a genetic disorder
characterized by elevated levels of total cholesterol (TC) and low-density
lipoprotein cholesterol (LDL-C). Guidelines recommend cholesterol-lowering
medication from 8 to 10 years of age and dietary recommendations. Little is known
about the diet of FH children and the effect of dietary counseling. The aim of
the study was to describe the diet of FH children with respect to fat quality,
and to investigate if dietary counseling improved lipid profile. METHODS: Fifty
four FH children (5-18 years) were included in the study and dietary intake was
recorded with a pre-coded food diary for four days. Information about plasma
lipid levels was obtained. RESULTS: Median intake of total fat, monounsaturated
fat, polyunsaturated fat (PUFA) and saturated fat (SFA) was 30.8, 10.4, 5.9 and
12.0 E %, respectively. Among non-statin treated FH children, SFA intake was
significantly correlated with TC, LDL-C and apolipoprotein (apo) B (rsp = 0.55; p
= 0.004, rsp = 0.46; p = 0.02, and rsp = 0.45; p = 0.02, respectively), and
PUFA/SFA ratio significantly inversely correlated with TC (rsp = -0.42; p =
0.03). Compared to the first visit, non-statin and non-plant sterol treated FH
children (n = 10) had significantly reduced levels of TC (p < 0.01), LDL-C (p =
0.01), high-density lipoprotein cholesterol (p = 0.02), apo B (p = 0.05) and apo
A-1 (p = 0.02) levels at a later visit. CONCLUSIONS: FH children had a higher
intake of SFA than recommended and the SFA intake was positively correlated with
plasma TC, LDL-C and apo B levels in FH children not using statins. Importantly,
the plasma lipid profile was improved in FH children after dietary counseling
where focus was on reducing intake of SFA and dietary cholesterol.
PMID- 27494448
TI - Long-term effects of weight loss with a very-low carbohydrate, low saturated fat
diet on flow mediated dilatation in patients with type 2 diabetes: A randomised
controlled trial.
AB - BACKGROUND AND AIMS: Very-low carbohydrate diets can improve glycaemic control in
patients with type 2 diabetes (T2DM). However, compared to traditional higher
carbohydrate, low fat (HighCHO) diets, they have been associated with impaired
endothelial function (measured by flow mediated dilatation [FMD]) that is
possibly related to saturated fat. This study aimed to examine the effects of a
12-month hypocaloric very-low carbohydrate, low saturated fat (LowCHO) diet
compared to an isocaloric HighCHO diet. METHODS: One hundred and fifteen obese
patients with T2DM (age:58.4 +/- 0.7 [SEM] yr, BMI:34.6 +/- 0.4 kg/m(2),
HbA1c:7.33 [56.3 mmol/mol] +/- 0.10%) were randomised to consume an energy
restricted LowCHO diet (Carb:Pro:Fat:Sat-Fat 14:28:58: < 10% energy; n = 58) or
isocaloric HighCHO diet (53:17:30: < 10%; n = 57) whilst undertaking exercise (60
min, 3/wk). Bodyweight, HbA1c and FMD were assessed. RESULTS: Seventy eight
participants completed the intervention (LowCHO = 41, HighCHO = 37). Both groups
experienced similar reductions in weight and HbA1c (-10.6 +/- 0.7 kg, -1.05 +/-
0.10%; p < 0.001 time, p >= 0.48 time * diet). FMD did not change (p = 0.11 time,
p = 0.20 time * diet). CONCLUSIONS: In patients with obesity and T2DM, HighCHO
diet and LowCHO diet have similar effects on endothelial function.
PMID- 27494449
TI - Gender and age effects on risk factor-based prediction of coronary artery calcium
in symptomatic patients: A Euro-CCAD study.
AB - BACKGROUND AND AIMS: The influence of gender and age on risk factor prediction of
coronary artery calcification (CAC) in symptomatic patients is unclear. METHODS:
From the European Calcific Coronary Artery Disease (EURO-CCAD) cohort, we
retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark,
France, Germany, Italy, Spain and USA. All of them underwent risk factor
assessment and CT scanning for CAC scoring. RESULTS: The prevalence of CAC among
females was lower than among males in all age groups. Using multivariate logistic
regression, age, dyslipidaemia, hypertension, diabetes and smoking were
independently predictive of CAC presence in both genders. In addition to a
progressive increase in CAC with age, the most important predictors of CAC
presence were dyslipidaemia and diabetes (beta = 0.64 and 0.63, respectively) in
males and diabetes (beta = 1.08) followed by smoking (beta = 0.68) in females;
these same risk factors were also important in predicting increasing CAC scores.
There was no difference in the predictive ability of diabetes, hypertension and
dyslipidaemia in either gender for CAC presence in patients aged <50 and 50-70
years. However, in patients aged >70, only dyslipidaemia predicted CAC presence
in males and only smoking and diabetes were predictive in females. CONCLUSIONS:
In symptomatic patients, there are significant differences in the ability of
conventional risk factors to predict CAC presence between genders and between
patients aged <70 and >=70, indicating the important role of age in predicting
CAC presence.
PMID- 27494450
TI - To evaluate the prevalence of symptomatic and non-symptomatic ductus arteriosus
and accuracy of physical signs in diagnosing PDA in preterm infants using blinded
comparison of clinical and echocardiographic findings during the first week of
life: a prospective observational study from Iran.
AB - AIMS: To evaluate the prevalence of symptomatic and non-symptomatic ductus
arteriosus (PDA) and accuracy of physical signs in diagnosing PDA in preterm
infants using blinded comparison of clinical and echocardiographic findings
during the first week of life. METHODS AND MATERIAL: This prospective
observational cross-sectional study enrolled 200 preterm infants, who underwent
echocardiography on 4th-7th postnatal day. The neonates who were diagnosed to
have PDA on echo were observed for clinical features of PDA to label it
symptomatic PDA. Symptomatic PDA was defined as detecting one or all of these
symptoms in a neonate with PDA: bounding pulse, pericardial hyperactivity,
systolic or continuous murmur. RESULTS: Forty-five infants had PDA on
echocardiography. 66.7% neonates with PDA were symptomatic and the most prevalent
symptom in them was heart murmur (100%) either alone or combined with other
clinical features. Isolated murmur was seen in 31.2%, murmur and hyperdynamic
precordium was seen in 8.8%, murmur and bounding pulses were seen in 6.67% and
all three features simultaneously were seen in 20% of infants. The sensitivity of
murmur for diagnosing symptomatic PDA was highest. CONCLUSION: Presence of murmur
is the most important clinical feature for diagnosis of symptomatic PDA and has
good specificity.
PMID- 27494451
TI - Elucidating the Mechanism of Zn(2+) Sensing by a Bipyridine Probe Based on Two
Photon Absorption.
AB - In this work, we examine, by means of computational methods, the mechanism of
Zn(2+) sensing by a bipyridine-centered, D-pi-A-pi-D-type ratiometric molecular
probe. According to recently published experimental data [Divya, K. P.; Sreejith,
S.; Ashokkumar, P.; Yuzhan, K.; Peng, Q.; Maji, S. K.; Tong, Y.; Yu, H.; Zhao,
Y.; Ramamurthy, P.; Ajayaghosh, A. A ratiometric fluorescent molecular probe with
enhanced two-photon response upon Zn(2+) binding for in vitro and in vivo
bioimaging. Chem. Sci. 2014, 5, 3469-3474], after coordination to zinc ions the
probe exhibits a large enhancement of the two-photon absorption cross section.
The goal of our investigation was to elucidate the mechanism behind this
phenomenon. For this purpose, linear and nonlinear optical properties of the
unbound (cation-free) and bound probe were calculated, including the influence of
solute-solvent interactions, implicitly using a polarizable continuum model and
explicitely employing the QM/MM approach. Because the results of the calculations
indicate that many conformers of the probe are energetically accessible at room
temperature in solution and hence contribute to the signal, structure-property
relationships were also taken into account. Results of our simulations
demonstrate that the one-photon absorption bands for both the unbound and bound
forms correspond to the bright pi -> pi* transition to the first excited state,
which, on the other hand, exhibits negligible two-photon activity. On the basis
of the results of the quadratic response calculations, we put forward a notion
that it is the second excited state that gives the strong signal in the
experimental nonlinear spectrum. To explain the differences in the two-photon
absorption activity for the two lowest-lying excited states and nonlinear
response enhancement upon binding, we employed the generalized few-state model
including the ground, first, and second excited states. The analysis of the
optical channel suggests that the large two-photon response is due to the
coordination-induced increase of the transition moment from the first to the
second excited state.
PMID- 27494452
TI - Endoscopic suturing for the prevention of stent migration in benign upper
gastrointestinal conditions: a comparative multicenter study.
PMID- 27494453
TI - Endoscopic treatment of sporadic small duodenal and ampullary neuroendocrine
tumors.
AB - Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare,
their optimal management has not been clearly established. The aim of this study
was to evaluate the feasibility and outcome of endoscopic treatment of duodenal
NETs. Patients and methods: We reviewed the files of all patients who underwent
endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and
2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs < 20 mm
were included. Treatment consisted of endoscopic mucosal resection in 19 cases,
and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15
cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At
post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions
were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All
NETs were well differentiated. A total of 27 lesions were classified as grade 1
and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions,
respectively. Three R1 patients underwent additional surgical treatment, with no
residual tumor on the surgical specimen but with positive metastatic lymph nodes
in two cases. One patient was lost to follow-up. Finally, 24 patients were
included in the follow-up analysis. The median follow-up period was 56 months
(range 6 - 175 months). Two patients presented a tumor recurrence during the
follow-up period. Conclusions: Endoscopic treatment of small duodenal NETs was
associated with significant morbidity, a difficulty in obtaining an R0 specimen,
and the risk of lymph node metastasis. Nevertheless, it represents an interesting
alternative in small grade 1 duodenal lesions and in patients at high surgical
risk.
PMID- 27494454
TI - All-cause mortality after ERCP.
AB - Background and study aims: This study aimed to externally validate a recently
developed English model for the prediction of 30-day mortality after endoscopic
retrograde cholangiopancreatography (ERCP). Real-world mortality data beyond 30
days post-ERCP are scarce; thus, the study also aimed to develop a prediction
model for mortality up to 12 months post-ERCP. Patients and methods: All patients
who underwent their first ERCP during a 3-year period (n = 16 478), as identified
from the Swedish Hospital Discharge Registry, were linked to the Swedish Death
Registry. Factors associated with all-cause mortality up to 12 months post-ERCP
were identified by Cox proportional hazards analysis. A prediction model was
developed. Results: Post-ERCP mortality was 5 % at 30 days and increased to 11.9
% at 3 months. The English model slightly overpredicted 30-day mortality, which
was corrected with recalibration. Discriminant validity of the recalibrated model
was very good (c-statistic = 0.82). Independent predictors of medium-term
mortality were: emergency admission (hazard ratio [HR] 1.48), cancer (HR 3.79),
noncancer co-morbidity (1.33), gallstone-related diagnosis (HR 0.21), and age (HR
4.86 for >= 85 years vs. < 55 years). The c-statistic for 3 - 12-month mortality
was 0.86 - 0.88. Specific ERCP complication codes were identified in 1.8 % of
deaths within 30 days post-ERCP (0.09 % of ERCPs), and 75 % of deaths (18 % of
ERCPs) within 1 year post-ERCP were due to cancer. Conclusions: Mortality doubled
from 30 days to 3 months post-ERCP, but it was attributed mainly to underlying
disease, notably cancer, and infrequently to ERCP-related causes. A previously
developed model predicting 30-day mortality was externally validated. A model
accurately predicting mortality up to 12 months post-ERCP was developed.
PMID- 27494455
TI - Impact of an automated system for endocytoscopic diagnosis of small colorectal
lesions: an international web-based study.
AB - Background and study aims: Optical diagnosis of colorectal polyps is expected to
improve the cost-effectiveness of colonoscopy, but achieving a high accuracy is
difficult for trainees. Computer-aided diagnosis (CAD) is therefore receiving
attention as an attractive tool. This study aimed to validate the efficacy of the
latest CAD model for endocytoscopy (380-fold ultra-magnifying endoscopy).
Patients and methods: This international web-based trial was conducted between
August and November 2015. A web-based test comprising one white-light and one
endocytoscopic image of 205 small colorectal polyps (<= 10 mm) from 123 patients
was undertaken by both CAD and by endoscopists (three experts and ten non-experts
from three countries). Outcome measures were accuracy in identifying neoplastic
change in diminutive (<= 5 mm) and small (<= 10 mm) polyps, and accuracy in
predicting post-polypectomy surveillance intervals according to current
guidelines for high confidence optical diagnoses of diminutive polyps. Results:
Of the 205 small polyps (147 neoplastic and 58 non-neoplastic), 139 were
diminutive. CAD was accurate for 89 % (95 % confidence interval [CI] 83 % - 94 %)
of diminutive polyps and 89 % (84 % - 93 %) of small polyps, which was
significantly greater than results for the non-experts (73 % [71 % - 76 %], P <
0.001; and 76 % [74 % - 78 %], P < 0.001, respectively) and comparable with the
experts' results (90 % [87 % - 93 %], P = 0.703; and 91 % [89 % - 93 %], P =
0.106, respectively). The surveillance interval predicted by CAD provided 98 %
(93 % - 100 %) and 96 % (91 % - 99 %) agreement with pathology-directed intervals
of the European and American guidelines, respectively. Conclusions: The use of
CAD in endocytoscopy can be effective in the management of diminutive/small
colorectal polyps.UMIN Clinical Trial Registry: UMIN000018185.
PMID- 27494456
TI - C9ORF72 is a GDP/GTP exchange factor for Rab8 and Rab39 and regulates autophagy.
AB - Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS-FTD) are
devastating neurodegenerative disease affecting motoneurons from the spinal chord
and neurons from the frontal and temporal cortex, respectively. The most common
genetic cause for ALS-FTD is an expansion of GGGGCC repeats within the first
intron of the C9ORF72 gene. However, little is known on the function of C9ORF72.
Recently, other and we found that C9ORF72 forms a stable complex with the SMCR8
and WDR41 proteins. This complex acts as a GDP/GTP exchange factor for the small
RAB GTPases Rab8a and Rab39b. Since Rab8 and Rab39 are involved in
macroautophagy, we tested the role of C9ORF72 in this mechanism. Decrease
expression of C9ORF72 in neuronal cultures leads to autophagy dysfunction
characterized by accumulation of aggregates of p62/SQSTM1. However, loss of
C9ORF72 expression does not cause major neuronal cell death, suggesting that a
second stress may be required to promote cell toxicity. Intermediate size of
polyglutamine repeats within Ataxin-2 (ATXN2) is an important genetic modifier of
ALS-FTD. We found that decrease expression of C9ORF72 synergizes the toxicity and
aggregation of ATXN2 with intermediate size of polyglutamine (30Q). Overall, our
data suggest that reduce expression of C9ORF72 causes suboptimal autophagy that
sensitizes neurons to a second stress. These data suggest that reduce expression
of C9ORF72 may partly contribute to ALS-FTD pathogenesis.
PMID- 27494457
TI - Acute Bilateral Toxic Endotheliitis Following Alcohol Consumption.
AB - A 28-year-old male farmer presented to our emergency service with bilateral
painful visual loss for the past 7 days that occurred suddenly after alcohol
consumption. Examination showed bilateral central corneal epithelial defects, 3+
stromal edema, and cortical cataracts. After treatment with oral and topical
corticosteroids for 4 weeks the corneal edema had subsided completely with mild
anterior stromal scarring. Rapid progression of cataract to intumescent stage
warranted sequential cataract surgeries 1 and 2 months after first presentation.
Postoperatively, visual acuity recovered to 20/20 and 20/30 in the right and left
eye respectively. This case highlights the extremely rare presentation of
bilateral alcohol-induced toxic endothelitis, which recovered after intensive
corticosteroid therapy.
PMID- 27494458
TI - Toxicity of twenty-two plant essential oils against pathogenic bacteria of
vegetables and mushrooms.
AB - ASBTRACT Toxicity of twenty-two essential oils to three bacterial pathogens in
different horticultural systems: Xanthomonas campestris pv. phaseoli (causing
blight of bean), Clavibacter michiganensis subsp. michiganensis (bacterial wilt
and canker of tomato), and Pseudomonas tolaasii (causal agent of bacterial brown
blotch on cultivated mushrooms) was tested. Control of bacterial diseases is very
difficult due to antibiotic resistance and ineffectiveness of chemical products,
to that essential oils offer a promising alternative. Minimal inhibitory and
bactericidal concentrations are determined by applying a single drop of oil onto
the inner side of each plate cover in macrodilution assays. Among all tested
substances, the strongest and broadest activity was shown by the oils of
wintergreen (Gaultheria procumbens), oregano (Origanum vulgare), and lemongrass
(Cymbopogon flexuosus. Carvacrol (64.0-75.8%) was the dominant component of
oregano oils, while geranial (40.7%) and neral (26.7%) were the major
constituents of lemongrass oil. Xanthomonas campestris pv. phaseoli was the most
sensitive to plant essential oils, being susceptible to 19 oils, while 11 oils
were bactericidal to the pathogen. Sixteen oils inhibited the growth of
Clavibacter michiganensis subsp. michiganensis and seven oils showed bactericidal
effects to the pathogen. The least sensitive species was Pseudomonas tolaasii as
five oils inhibited bacterial growth and two oils were bactericidal. Wintergreen,
oregano, and lemongrass oils should be formulated as potential biochemical
bactericides against different horticultural pathogens.
PMID- 27494459
TI - Effect of cigarette smoke on monocyte procoagulant activity: Focus on platelet
derived brain-derived neurotrophic factor (BDNF).
AB - Cigarette smoke (CS) activates platelets, promotes vascular dysfunction, and
enhances Tissue Factor (TF) expression in blood monocytes favoring pro-thrombotic
states. Brain-derived neurotrophic factor (BDNF), a member of the family of
neurotrophins involved in survival, growth, and maturation of neurons, is
released by activated platelets (APLTs) and plays a role in the cardiovascular
system. The effect of CS on circulating levels of BDNF is controversial and the
function of circulating BDNF in atherothrombosis is not fully understood. Here,
we have shown that human platelets, treated with an aqueous extract of CS (CSE),
released BDNF in a dose-dependent manner. In addition, incubation of human
monocytes with BDNF or with the supernatant of platelets activated with CSE
increased TF activity by a Tropomyosin receptor kinase B (TrkB)-dependent
mechanism. Finally, comparing serum and plasma samples of 12 male never smokers
(NS) and 29 male active smokers (AS) we observed a significant increase in
microparticle-associated TF activity (MP-TF) as well as BDNF in AS, while in
serum, BDNF behaved oppositely. Taken together these findings suggest that
platelet-derived BDNF is involved in the regulation of TF activity and that CS
plays a role in this pathway by favoring a pro-atherothrombotic state.
PMID- 27494461
TI - Rashba Spin-Orbit Coupling, Strong Interactions, and the BCS-BEC Crossover in the
Ground State of the Two-Dimensional Fermi Gas.
AB - The recent experimental realization of spin-orbit coupled Fermi gases provides a
unique opportunity to study the interplay between strong interaction and spin
orbit coupling (SOC) in a tunable, disorder-free system. We present here
precision ab initio numerical results on the two-dimensional, unpolarized,
uniform Fermi gas with attractive interactions and Rashba SOC. Using the
auxiliary-field quantum Monte Carlo method and incorporating recent algorithmic
advances, we carry out exact calculations on sufficiently large system sizes to
provide accurate results systematically as a function of experimental parameters.
We obtain the equation of state, the momentum distributions, the pseudospin
correlations, and the pair wave functions. Our results help illuminate the rich
pairing structure induced by SOC, and provide benchmarks for theory and guidance
to future experimental efforts.
PMID- 27494462
TI - Experimental Demonstration of Self-Guided Quantum Tomography.
AB - Traditional methods of quantum state characterization are impractical for systems
of more than a few qubits due to exponentially expensive postprocessing and data
storage and lack robustness against errors and noise. Here, we experimentally
demonstrate self-guided quantum tomography performed on polarization photonic
qubits. The quantum state is iteratively learned by optimizing a projection
measurement without any data storage or postprocessing. We experimentally
demonstrate robustness against statistical noise and measurement errors on single
qubit and entangled two-qubit states.
PMID- 27494463
TI - Scalable Dissipative Preparation of Many-Body Entanglement.
AB - We present a technique for the dissipative preparation of highly entangled
multiparticle states of atoms coupled to common oscillator modes. By combining
local spontaneous emission with coherent couplings, we engineer many-body
dissipation that drives the system from an arbitrary initial state into a
Greenberger-Horne-Zeilinger state. We demonstrate that using our technique highly
entangled steady states can be prepared efficiently in a time that scales
polynomially with the system size. Our protocol assumes generic couplings and
will thus enable the dissipative production of multiparticle entanglement in a
wide range of physical systems. As an example, we demonstrate the feasibility of
our scheme in state-of-the-art trapped-ion systems.
PMID- 27494464
TI - Diffusive and Subdiffusive Spin Transport in the Ergodic Phase of a Many-Body
Localizable System.
AB - We study high temperature spin transport in a disordered Heisenberg chain in the
ergodic regime. By employing a density matrix renormalization group technique for
the study of the stationary states of the boundary-driven Lindblad equation we
are able to study extremely large systems (400 spins). We find both a diffusive
and a subdiffusive phase depending on the strength of the disorder and on the
anisotropy parameter of the Heisenberg chain. Studying finite-size effects, we
show numerically and theoretically that a very large crossover length exists that
controls the passage of a clean-system dominated dynamics to one observed in the
thermodynamic limit. Such a large length scale, being larger than the sizes
studied before, explains previous conflicting results. We also predict spatial
profiles of magnetization in steady states of generic nondiffusive systems.
PMID- 27494465
TI - Modular Hamiltonian for Excited States in Conformal Field Theory.
AB - We present a novel replica trick that computes the relative entropy of two
arbitrary states in conformal field theory. Our replica trick is based on the
analytic continuation of partition functions that break the Z_{n} replica
symmetry. It provides a method for computing arbitrary matrix elements of the
modular Hamiltonian corresponding to excited states in terms of correlation
functions. We show that the quantum Fisher information in vacuum can be expressed
in terms of two-point functions on the replica geometry. We perform sample
calculations in two-dimensional conformal field theories.
PMID- 27494466
TI - Precise QCD Predictions for the Production of Dijet Final States in Deep
Inelastic Scattering.
AB - The production of two-jet final states in deep inelastic scattering is an
important QCD precision observable. We compute it for the first time to next-to
next-to-leading order (NNLO) in perturbative QCD. Our calculation is fully
differential in the lepton and jet variables and allows one to impose cuts on the
jets in both the laboratory and the Breit frame. We observe that the NNLO
corrections are moderate in size, except at kinematical edges, and that their
inclusion leads to a substantial reduction of the scale variation uncertainty on
the predictions. Our results will enable the inclusion of deep inelastic dijet
data in precision phenomenology studies.
PMID- 27494468
TI - Cool Quark Matter.
AB - We generalize the state-of-the-art perturbative equation of state of cold quark
matter to nonzero temperatures, needed in the description of neutron star mergers
and core collapse processes. The new result is accurate to O(g^{5}) in the gauge
coupling, and is based on a novel framework for dealing with the infrared
sensitive soft field modes of the theory. The zero Matsubara mode sector is
treated via a dimensionally reduced effective theory, while the soft nonzero
modes are resummed using the hard thermal loop approximation. This combination of
known effective descriptions offers unprecedented access to small but nonzero
temperatures, both in and out of beta equilibrium.
PMID- 27494469
TI - Transmission Microscopy with Nanometer Resolution Using a Deterministic Single
Ion Source.
AB - We realize a single particle microscope by using deterministically extracted
laser-cooled ^{40}Ca^{+} ions from a Paul trap as probe particles for
transmission imaging. We demonstrate focusing of the ions to a spot size of 5.8+/
1.0 nm and a minimum two-sample deviation of the beam position of 1.5 nm in the
focal plane. The deterministic source, even when used in combination with an
imperfect detector, gives rise to a fivefold increase in the signal-to-noise
ratio as compared with conventional Poissonian sources. Gating of the detector
signal by the extraction event suppresses dark counts by 6 orders of magnitude.
We implement a Bayes experimental design approach to microscopy in order to
maximize the gain in spatial information. We demonstrate this method by
determining the position of a 1 MUm circular hole structure to a precision of
2.7 nm using only 579 probe particles.
PMID- 27494470
TI - Monitoring Nonadiabatic Electron-Nuclear Dynamics in Molecules by Attosecond
Streaking of Photoelectrons.
AB - Streaking of photoelectrons has long been used for the temporal characterization
of attosecond extreme ultraviolet pulses. When the time-resolved photoelectrons
originate from a coherent superposition of electronic states, they carry
additional phase information, which can be retrieved by the streaking technique.
In this contribution we extend the streaking formalism to include coupled
electron and nuclear dynamics in molecules as well as initial coherences. We
demonstrate how streaked photoelectrons offer a novel tool for monitoring
nonadiabatic dynamics as it occurs in the vicinity of conical intersections and
avoided crossings. Streaking can provide high time resolution direct signatures
of electronic coherences, which affect many primary photochemical and biological
events.
PMID- 27494471
TI - One Photon Can Simultaneously Excite Two or More Atoms.
AB - We consider two separate atoms interacting with a single-mode optical or
microwave resonator. When the frequency of the resonator field is twice the
atomic transition frequency, we show that there exists a resonant coupling
between one photon and two atoms, via intermediate virtual states connected by
counterrotating processes. If the resonator is prepared in its one-photon state,
the photon can be jointly absorbed by the two atoms in their ground state which
will both reach their excited state with a probability close to one. Like
ordinary quantum Rabi oscillations, this process is coherent and reversible, so
that two atoms in their excited state will undergo a downward transition jointly
emitting a single cavity photon. This joint absorption and emission process can
also occur with three atoms. The parameters used to investigate this process
correspond to experimentally demonstrated values in circuit quantum
electrodynamics systems.
PMID- 27494473
TI - Accessing Extreme Spatiotemporal Localization of High-Power Laser Radiation
through Transformation Optics and Scalar Wave Equations.
AB - Although tightly focused intense ultrashort laser pulses are used in many
applications from nano-processing to warm dense matter physics, their nonparaxial
propagation implies the use of numerical simulations with vectorial wave
equations or exact Maxwell solvers that have serious limitations and thus have
hindered progress in this important field up to now. Here we present an elegant
and robust solution that allows one to map the problem on one that can be
addressed by simple scalar wave equations. The solution is based on a
transformation optics approach and its validity is demonstrated in both the
linear and the nonlinear regime. Our solution allows accessing challenging
problems of extreme spatiotemporal localization of high power laser radiation
that remain almost unexplored theoretically until now.
PMID- 27494472
TI - Solid-State Source of Subcycle Pulses in the Midinfrared.
AB - We demonstrate a robust, all-solid-state approach for the generation of
microjoule subcycle pulses in the midinfrared through a cascade of carefully
optimized parametric-amplification, difference-frequency-generation, spectral
broadening, and chirp-compensation stages. This method of subcycle waveform
generation becomes possible due to an unusual, ionization-assisted solid-state
pulse self-compression dynamics, where highly efficient spectral broadening is
enabled by ultrabroadband four-wave parametric amplification phase matched near
the zero-group-velocity wavelength of the material.
PMID- 27494474
TI - Spectrally Enhancing Near-Field Radiative Transfer between Metallic Gratings by
Exciting Magnetic Polaritons in Nanometric Vacuum Gaps.
AB - In the present Letter, we theoretically demonstrate that near-field radiative
transport between one-dimensional periodic grating microstructures separated by
nanometer vacuum gaps can be spectrally enhanced by exciting magnetic polaritons.
Fluctuational electrodynamics that incorporates scattering matrix theory with
rigorous coupled-wave analysis is employed to exactly calculate the near-field
radiative flux between two metallic gratings. In addition to the well-known
coupled surface plasmon polaritons, the radiative flux can be also spectrally
enhanced due to the magnetic polariton, which is excited in the gap between the
grating ridges. The mechanism of magnetic polaritons in the near-field radiative
transport are elucidated in detail, while the unusual enhancement cannot be
predicted by either Derjaguin's or the effective medium approximations. The
effects of the vacuum gap distance and grating geometry parameters between the
two gratings are investigated. The findings will open a new way to spectrally
control near-field radiative transfer by magnetic polaritons with micro- or
nanostructured metamaterials, which holds great potential for improving the
performance of energy systems like near-field thermophotovoltaics.
PMID- 27494475
TI - Cavitation-Induced Fracture Causes Nanocorrugations in Brittle Metallic Glasses.
AB - Brittle metallic glasses exhibit a unique and intriguing fracture morphology of
periodic nanocorrugations whose spacing and amplitude are of the order of tens of
nanometers. We show through continuum simulations that they fail by spontaneous
and simultaneous cavitation within multiple weak zones arising due to intrinsic
atomic density fluctuations ahead of a notch tip. Dynamic crack growth would then
occur along curved but narrowly confined shear bands that link the growing
cavities. This mechanism involves little dissipation and also explains the
formation of nanocorrugations.
PMID- 27494476
TI - Observation of Double Impurity Critical Gradients for Electromagnetic Turbulence
Excitation in Tokamak Plasmas.
AB - The impact of impurity ions on a pedestal has been investigated in the HL-2A
Tokamak, at the Southwestern Institute of Physics, Chengdu, China. Experimental
results have clearly shown that during the H-mode phase, an electromagnetic
turbulence was excited in the edge plasma region, where the impurity ions
exhibited a peaked profile. It has been found that double impurity critical
gradients are responsible for triggering the turbulence. Strong stiffness of the
impurity profile has been observed during cyclic transitions between the I-phase
and H-mode regime. The results suggest that the underlying physics of the self
regulated edge impurity profile offers the possibility for an active control of
the pedestal dynamics via pedestal turbulence.
PMID- 27494477
TI - Dislocation Structure and Mobility in hcp ^{4}He.
AB - Using path-integral Monte Carlo simulations, we assess the core structure and
mobility of the screw and edge basal-plane dislocations in hcp ^{4}He. Our
findings provide key insights into recent interpretations of giant plasticity and
mass flow junction experiments. First, both dislocations are dissociated into
nonsuperfluid Shockley partial dislocations separated by ribbons of stacking
fault, suggesting that they are unlikely to act as one-dimensional channels that
may display Luttinger-liquid-like behavior. Second, the centroid positions of the
partial cores are found to fluctuate substantially, even in the absence of
applied shear stresses. This implies that the lattice resistance to motion of the
partial dislocations is negligible, consistent with the recent experimental
observations of giant plasticity. Further results indicate that both the
structure of the partial cores and the zero-point fluctuations play a role in
this extreme mobility.
PMID- 27494478
TI - Topological Instabilities in ac-Driven Bosonic Systems.
AB - Under nonequilibrium conditions, bosonic modes can become dynamically unstable
with an exponentially growing occupation. On the other hand, topological band
structures give rise to symmetry protected midgap states. In this Letter, we
investigate the interplay of instability and topology. Thereby, we establish a
general relation between topology and instability under ac driving. We apply our
findings to create dynamical instabilities which are strongly localized at the
boundaries of a finite-size system. As these localized instabilities are
protected by symmetry, they can be considered as topological instabilities.
PMID- 27494479
TI - Geometric Origin of Superfluidity in the Lieb-Lattice Flat Band.
AB - The ground state and transport properties of the Lieb lattice flat band in the
presence of an attractive Hubbard interaction are considered. It is shown that
the superfluid weight can be large even for an isolated and strictly flat band.
Moreover the superfluid weight is proportional to the interaction strength and to
the quantum metric, a band structure quantity derived solely from the flat-band
Bloch functions. These predictions are amenable to verification with ultracold
gases and may explain the anomalous behavior of the superfluid weight of high
T_{c} superconductors.
PMID- 27494480
TI - Connecting Local Yield Stresses with Plastic Activity in Amorphous Solids.
AB - In model amorphous solids produced via differing quench protocols, a strong
correlation is established between local yield stress measured by direct local
probing of shear stress thresholds and the plastic rearrangements observed during
remote loading in shear. This purely local measure shows a higher predictive
power for identifying sites of plastic activity when compared with more
conventional structural properties. Most importantly, the sites of low local
yield stress, thus defined, are shown to be persistent, remaining predictive of
deformation events even after fifty or more such plastic rearrangements. This
direct and nonperturbative approach gives access to relevant transition pathways
that control the stability of amorphous solids. Our results reinforce the
relevance of modeling plasticity in amorphous solids based on a gradually
evolving population of discrete and local zones preexisting in the structure.
PMID- 27494481
TI - Real-Time Examination of Atomistic Mechanisms during Shock-Induced Structural
Transformation in Silicon.
AB - The experimental determination of atomistic mechanisms linking crystal structures
during a compression-driven solid-solid phase transformation is a long-standing
and challenging scientific objective. Using new capabilities at the Dynamic
Compression Sector at the Advanced Photon Source, the structure of shocked Si at
19 GPa was identified as simple hexagonal, and the lattice orientations between
ambient cubic diamond and simple hexagonal structures were related. The approach
is general and provides a powerful new method for examining atomistic mechanisms
during stress-induced structural changes.
PMID- 27494482
TI - Universal Non-Debye Scaling in the Density of States of Amorphous Solids.
AB - At the jamming transition, amorphous packings are known to display anomalous
vibrational modes with a density of states (DOS) that remains constant at low
frequency. The scaling of the DOS at higher packing fractions remains, however,
unclear. One might expect to find a simple Debye scaling, but recent results from
effective medium theory and the exact solution of mean-field models both predict
an anomalous, non-Debye scaling. Being mean-field in nature, however, these
solutions are only strictly valid in the limit of infinite spatial dimension, and
it is unclear what value they have for finite-dimensional systems. Here, we study
packings of soft spheres in dimensions 3 through 7 and find, away from jamming, a
universal non-Debye scaling of the DOS that is consistent with the mean-field
predictions. We also consider how the soft mode participation ratio evolves as
dimension increases.
PMID- 27494483
TI - Self-Organized Growth, Structure, and Magnetism of Monatomic Transition-Metal
Oxide Chains.
AB - We report on the self-organized growth of monatomic transition-metal oxide chains
of (3*1) periodicity and unusual MO_{2} stoichiometry (M=Ni, Co, Fe, Mn) on
Ir(100). We analyze their structural and magnetic properties by means of
quantitative LEED, STM, and density functional theory (DFT) calculations. LEED
analyses reveal a fascinating common atomic structure in which the transition
metal atoms sit above a missing-row structure of the surface and are coupled to
the substrate only via oxygen atoms. This structure is confirmed by DFT
calculations with structural parameters deviating by less than 1.7 pm. The DFT
calculations predict that the NiO_{2} chains are nonmagnetic, CoO_{2} chains are
ferromagnetic, while FeO_{2} and MnO_{2} are antiferromagnetic. All structures
show only weak magnetic interchain coupling. Further, we demonstrate the growth
of oxide chains of binary alloys of Co and Ni or Fe on Ir(100), which allows us
to produce well-controlled ensembles of ferromagnetic chains of different lengths
separated by nonmagnetic or antiferromagnetic segments.
PMID- 27494484
TI - Long-Term Repellency of Liquids by Superoleophobic Surfaces.
AB - Applications of superoleophobic surfaces depend on the stability of the air
cushion formed under liquid drops. To analyze the longevity of air cushions we
used reflection-interference contrast microscopy (RICM) for drops on a porous
fractal-like structure of sintered nanoparticles. RICM permits us to monitor the
height of the air cushion with nanometer resolution. Whereas the air cushion
under all investigated liquids was stable on a time scale of a few seconds to
minutes and liquids rolled off, liquids with low surface tension penetrated the
coating on the time scale of hours and longer. The penetration speed showed a
power law dependence on time, dz/dt~t^{p}, the exponent p varying from -0.5 to
1.2. Thus, penetration is qualitatively different from the Lucas-Washburn law
that governs spontaneous capillary filling of porous structures.
PMID- 27494485
TI - Collapse of Ferromagnetism and Fermi Surface Instability near Reentrant
Superconductivity of URhGe.
AB - We present thermoelectric power and resistivity measurements in the ferromagnetic
superconductor URhGe for a magnetic field applied along the hard magnetization b
axis of the orthorhombic crystal. Reentrant superconductivity is observed near
the spin reorientation transition at H_{R}=12.75 T, where a first order
transition from the ferromagnetic to the polarized paramagnetic state occurs.
Special focus is given to the longitudinal configuration, where both the electric
and heat current are parallel to the applied field. The validity of the Fermi
liquid T^{2} dependence of the resistivity through H_{R} demonstrates clearly
that no quantum critical point occurs at H_{R}. Thus, the ferromagnetic
transition line at H_{R} becomes first order implying the existence of a
tricritical point at finite temperature. The enhancement of magnetic fluctuations
in the vicinity of the tricritical point stimulates the reentrance of
superconductivity. The abrupt sign change observed in the thermoelectric power
with the thermal gradient applied along the b axis together with the strong
anomalies in the other directions is definitive macroscopic evidence that in
addition a significant change of the Fermi surface appears through H_{R}.
PMID- 27494486
TI - Pseudogaps and Emergence of Coherence in Two-Dimensional Electron Liquids in
SrTiO_{3}.
AB - Using tunneling spectroscopy, we show that pseudogaps emerge in strongly
correlated, two-dimensional electron liquids in SrTiO_{3} quantum wells that are
tuned near a quantum critical point. Coherence peaks emerge at low temperatures
in quantum wells embedded in antiferromagnetic SmTiO_{3} that remain itinerant to
the lowest thickness. Quantum wells embedded in ferrimagnetic GdTiO_{3} that
become ferromagnetic at low temperatures show no indication of quasiparticle
coherence. They undergo a symmetry-lowering metal-to-insulator transition at the
lowest thicknesses that coincides with a vanishing single-particle density of
states (DOS) around the Fermi level. Both types of quantum wells show a power-law
depletion of the DOS at high energies. The results show that the different
pseudogap behaviors are closely correlated with the type of magnetism in the
proximity of the quantum wells and thus provide insights into the microscopic
mechanisms.
PMID- 27494467
TI - Observation of an Anomalous Line Shape of the eta^{'}pi^{+}pi^{-} Mass Spectrum
near the pp[over -] Mass Threshold in J/psi->gammaeta^{'}pi^{+}pi^{-}.
AB - Using 1.09*10^{9} J/psi events collected by the BESIII experiment in 2012, we
study the J/psi->gammaeta^{'}pi^{+}pi^{-} process and observe a significant
abrupt change in the slope of the eta^{'}pi^{+}pi^{-} invariant mass distribution
at the proton-antiproton (pp[over -]) mass threshold. We use two models to
characterize the eta^{'}pi^{+}pi^{-} line shape around 1.85 GeV/c^{2}: one that
explicitly incorporates the opening of a decay threshold in the mass spectrum
(Flatte formula), and another that is the coherent sum of two resonant
amplitudes. Both fits show almost equally good agreement with data, and suggest
the existence of either a broad state around 1.85 GeV/c^{2} with strong
couplings to the pp[over -] final states or a narrow state just below the pp[over
-] mass threshold. Although we cannot distinguish between the fits, either one
supports the existence of a pp[over -] moleculelike state or bound state with
greater than 7sigma significance.
PMID- 27494487
TI - Anomalous Hall Effect in a 2D Rashba Ferromagnet.
AB - Skew scattering on rare impurity configurations is shown to dominate the
anomalous Hall effect in a 2D Rashba ferromagnet. The mechanism originates in
scattering on rare impurity pairs separated by distances of the order of the
Fermi wavelength. The corresponding theoretical description goes beyond the
conventional noncrossing approximation. The mechanism provides the only
contribution to the anomalous Hall conductivity in the most relevant metallic
regime and strongly modifies previously obtained results for lower energies in
the leading order with respect to impurity strength.
PMID- 27494488
TI - Ultralow Thermal Conductivity in Full Heusler Semiconductors.
AB - Semiconducting half and, to a lesser extent, full Heusler compounds are promising
thermoelectric materials due to their compelling electronic properties with large
power factors. However, intrinsically high thermal conductivity resulting in a
limited thermoelectric efficiency has so far impeded their widespread use in
practical applications. Here, we report the computational discovery of a class of
hitherto unknown stable semiconducting full Heusler compounds with ten valence
electrons (X_{2}YZ, X=Ca, Sr, and Ba; Y=Au and Hg; Z=Sn, Pb, As, Sb, and Bi)
through high-throughput ab initio screening. These new compounds exhibit ultralow
lattice thermal conductivity kappa_{L} close to the theoretical minimum due to
strong anharmonic rattling of the heavy noble metals, while preserving high power
factors, thus resulting in excellent phonon-glass electron-crystal materials.
PMID- 27494490
TI - Fractionally Charged Zero-Energy Single-Particle Excitations in a Driven Fermi
Sea.
AB - A voltage pulse of a Lorentzian shape carrying half of the flux quantum excites
out of a zero-temperature Fermi sea an electron in a mixed state, which looks
like a quasiparticle with an effectively fractional charge e/2. A prominent
feature of such an excitation is a narrow peak in the energy distribution
function lying exactly at the Fermi energy MU. Another spectacular feature is
that the distribution function has symmetric tails around MU, which results in a
zero-energy excitation. This sounds improbable since at zero temperature all
available states below MU are fully occupied. The resolution lies in the fact
that such a voltage pulse also excites electron-hole pairs, which free some space
below MU and thus allow a zero-energy quasiparticle to exist. I discuss also how
to address separately electron-hole pairs and a fractionally charged zero-energy
excitation in an experiment.
PMID- 27494489
TI - Levy Flights due to Anisotropic Disorder in Graphene.
AB - We study transport properties of graphene with anisotropically distributed on
site impurities (adatoms) that are randomly placed on every third line drawn
along carbon bonds. We show that stripe states characterized by strongly
suppressed backscattering are formed in this model in the direction of the lines.
The system reveals Levy-flight transport in the stripe direction such that the
corresponding conductivity increases as the square root of the system length.
Thus, adding this type of disorder to clean graphene near the Dirac point
strongly enhances the conductivity, which is in stark contrast with a fully
random distribution of on-site impurities, which leads to Anderson localization.
The effect is demonstrated both by numerical simulations using the Kwant code and
by an analytical theory based on the self-consistent T-matrix approximation.
PMID- 27494492
TI - Giant Frictional Drag in Double Bilayer Graphene Heterostructures.
AB - We study the frictional drag between carriers in two bilayer graphene flakes
separated by a 2-5 nm thick hexagonal boron nitride dielectric. At temperatures
(T) lower than ~10 K, we observe a large anomalous negative drag emerging
predominantly near the drag layer charge neutrality. The anomalous drag
resistivity increases dramatically with reducing T, and becomes comparable to the
layer resistivity at the lowest T=1.5 K. At low T the drag resistivity exhibits
a breakdown of layer reciprocity. A comparison of the drag resistivity and the
drag layer Peltier coefficient suggests a thermoelectric origin of this anomalous
drag.
PMID- 27494491
TI - Negative Coulomb Drag in Double Bilayer Graphene.
AB - We report on an experimental measurement of Coulomb drag in a double quantum well
structure consisting of bilayer-bilayer graphene, separated by few layer
hexagonal boron nitride. At low temperatures and intermediate densities, a novel
negative drag response with an inverse sign is observed, distinct from the
momentum and energy drag mechanisms previously reported in double monolayer
graphene. By varying the device aspect ratio, the negative drag component is
suppressed and a response consistent with pure momentum drag is recovered. In the
momentum drag dominated regime, excellent quantitative agreement with the density
and temperature dependence predicted for double bilayer graphene is found.
PMID- 27494493
TI - Detection of Majorana Kramers Pairs Using a Quantum Point Contact.
AB - We propose a setup that integrates a quantum point contact (QPC) and a Josephson
junction on a quantum spin Hall sample, experimentally realizable in InAs/GaSb
quantum wells. The confinement due to both the QPC and the superconductor results
in a Kramers pair of Majorana zero-energy bound states when the superconducting
phases in the two arms differ by an odd multiple of pi across the Josephson
junction. We investigate the detection of these Majorana pairs with the
integrated QPC, and find a robust switching from normal to Andreev scattering
across the edges due to the presence of Majorana Kramers pairs. Such a switching
of the current represents a qualitative signature where multiterminal
differential conductances oscillate with alternating signs when the external
magnetic field is tuned. We show that this qualitative signature is also present
in current cross-correlations. Thus, the change of the backscattering current
nature affects both conductance and shot noise, the measurement of which offers a
significant advantage over quantitative signatures such as conductance
quantization in realistic measurements.
PMID- 27494494
TI - Topological Superconductivity on the Surface of Fe-Based Superconductors.
AB - As one of the simplest systems for realizing Majorana fermions, the topological
superconductor plays an important role in both condensed matter physics and
quantum computations. Based on ab initio calculations and the analysis of an
effective 8-band model with superconducting pairing, we demonstrate that the
three-dimensional extended s-wave Fe-based superconductors such as
Fe_{1+y}Se_{0.5}Te_{0.5} have a metallic topologically nontrivial band structure,
and exhibit a normal-topological-normal superconductivity phase transition on the
(001) surface by tuning the bulk carrier doping level. In the topological
superconductivity (TSC) phase, a Majorana zero mode is trapped at the end of a
magnetic vortex line. We further show that the surface TSC phase only exists up
to a certain bulk pairing gap, and there is a normal-topological phase transition
driven by the temperature, which has not been discussed before. These results
pave an effective way to realize the TSC and Majorana fermions in a large class
of superconductors.
PMID- 27494495
TI - Coherent Excited States in Superconductors due to a Microwave Field.
AB - We describe theoretically the depairing effect of a microwave field on diffusive
s-wave superconductors. The ground state of the superconductor is altered
qualitatively in analogy to the depairing due to a dc current. In contrast to dc
depairing, the density of states acquires, for microwaves with frequency
omega_{0}, steps at multiples of the photon energy Delta+/-nhomega_{0} and shows
an exponential-like tail in the subgap regime. We show that this ac depairing
explains the measured frequency shift of a superconducting resonator with
microwave power at low temperatures.
PMID- 27494496
TI - Magnetic Precursor of the Pressure-Induced Superconductivity in Fe-Ladder
Compounds.
AB - The pressure effects on the antiferromagentic orders in iron-based ladder
compounds CsFe_{2}Se_{3} and BaFe_{2}S_{3} have been studied using neutron
diffraction. With identical crystal structure and similar magnetic structures,
the two compounds exhibit highly contrasting magnetic behaviors under moderate
external pressures. In CsFe_{2}Se_{3} the ladders are brought much closer to each
other by pressure, but the stripe-type magnetic order shows no observable change.
In contrast, the stripe order in BaFe_{2}S_{3} undergoes a quantum phase
transition where an abrupt increase of Neel temperature by more than 50% occurs
at about 1 GPa, accompanied by a jump in the ordered moment. With its spin
structure unchanged, BaFe_{2}S_{3} enters an enhanced magnetic phase that bears
the characteristics of an orbital selective Mott phase, which is the true
neighbor of superconductivity emerging at higher pressures.
PMID- 27494497
TI - Magnetic Reversal of Electric Polarization with Fixed Chirality of Magnetic
Structure in a Chiral-Lattice Helimagnet MnSb_{2}O_{6}.
AB - The correlation between magnetic and dielectric properties has been investigated
for the single crystal of the chiral triangular-lattice helimagnet MnSb_{2}O_{6}.
We found that the spin-spiral plane in the ground state has a considerable
tilting from the (110) plane and that the sign of the spin-spiral tilting angle
is coupled to the clockwise or counterclockwise manner of spin rotation and
accordingly to the sign of magnetically induced electric polarization. This leads
to unique magnetoelectric responses such as the magnetic-field-induced selection
of a single ferroelectric domain as well as the reversal of electric polarization
just by a slight tilting of the magnetic field direction, where the chiral nature
of the crystal structure plays a crucial role through the coupling of the
chirality between the crystal and magnetic structures. Our results demonstrate
that crystallographic chirality can be an abundant source of novel
magnetoelectric functions with coupled internal degrees of freedom.
PMID- 27494498
TI - Optical Activation of Germanium Plasmonic Antennas in the Mid-Infrared.
AB - Impulsive interband excitation with femtosecond near-infrared pulses establishes
a plasma response in intrinsic germanium structures fabricated on a silicon
substrate. This direct approach activates the plasmonic resonance of the Ge
structures and enables their use as optical antennas up to the mid-infrared
spectral range. The optical switching lasts for hundreds of picoseconds until
charge recombination redshifts the plasma frequency. The full behavior of the
structures is modeled by the electrodynamic response established by an electron
hole plasma in a regular array of antennas.
PMID- 27494499
TI - Water Dielectric Effects in Planar Confinement.
AB - We investigate the dielectric profile of water confined between two planar polar
walls using atomistic molecular dynamics simulations. For a water slab thickness
below 1 nm the dielectric response is highly asymmetric: while the parallel
component slightly increases compared to bulk, the perpendicular one decreases
drastically due to anticorrelated polarization of neighboring water molecules. We
demonstrate the importance of the dielectric contribution due to flexible polar
headgroups and derive an effective dielectric tensorial box model suitable for
coarse-grained electrostatic modeling.
PMID- 27494500
TI - Guiding Catalytically Active Particles with Chemically Patterned Surfaces.
AB - Catalytically active Janus particles suspended in solution create gradients in
the chemical composition of the solution along their surfaces, as well as along
any nearby container walls. The former leads to self-phoresis, while the latter
gives rise to chemiosmosis, providing an additional contribution to self
motility. Chemiosmosis strongly depends on the molecular interactions between the
diffusing chemical species and the wall. We show analytically, using an
approximate "point-particle" approach, that by chemically patterning a planar
substrate one can direct the motion of Janus particles: the induced chemiosmotic
flows can cause particles to either "dock" at the chemical step between the two
materials or follow a chemical stripe. These theoretical predictions are
confirmed by full numerical calculations. Generically, docking occurs for
particles which tend to move away from their catalytic caps, while stripe
following occurs in the opposite case. Our analysis reveals the physical
mechanisms governing this behavior.
PMID- 27494501
TI - Curling Liquid Crystal Microswimmers: A Cascade of Spontaneous Symmetry Breaking.
AB - We report curling self-propulsion in aqueous emulsions of common mesogenic
compounds. Nematic liquid crystal droplets self-propel in a surfactant solution
with concentrations above the critical micelle concentration while undergoing
micellar solubilization [Herminghaus et al., Soft Matter 10, 7008 (2014)]. We
analyzed trajectories both in a Hele-Shaw geometry and in a 3D setup at variable
buoyancy. The coupling between the nematic director field and the convective flow
inside the droplet leads to a second symmetry breaking which gives rise to
curling motion in 2D. This is demonstrated through a reversible transition to
nonhelical persistent swimming by heating to the isotropic phase. Furthermore,
autochemotaxis can spontaneously break the inversion symmetry, leading to helical
trajectories in 3D.
PMID- 27494502
TI - Law of Localization in Chemical Reaction Networks.
AB - In living cells, chemical reactions are connected by sharing their products and
substrates, and form complex networks, e.g., metabolic pathways. Here we
developed a theory to predict the sensitivity, i.e., the responses of
concentrations and fluxes to perturbations of enzymes, from network structure
alone. Nonzero response patterns turn out to exhibit two characteristic features,
localization and hierarchy. We present a general theorem connecting sensitivity
with network topology that explains these characteristic patterns. Our results
imply that network topology is an origin of biological robustness. Finally, we
suggest a strategy to determine real networks from experimental measurements.
PMID- 27494503
TI - Defect-Mediated Morphologies in Growing Cell Colonies.
AB - Morphological trends in growing colonies of living cells are at the core of
physiological and evolutionary processes. Using active gel equations, which
include cell division, we show that shape changes during the growth can be
regulated by the dynamics of topological defects in the orientation of cells. The
friction between the dividing cells and underlying substrate drives anisotropic
colony shapes toward more isotropic morphologies, by mediating the number density
and velocity of topological defects. We show that the defects interact with the
interface at a specific interaction range, set by the vorticity length scale of
flows within the colony, and that the cells predominantly reorient parallel to
the interface due to division-induced active stresses.
PMID- 27494504
TI - Erratum: Implication of the Proton-Deuteron Radiative Capture for Big Bang
Nucleosynthesis [Phys. Rev. Lett. 116, 102501 (2016)].
AB - This corrects the article DOI: 10.1103/PhysRevLett.116.102501.
PMID- 27494506
TI - Electron-phonon interaction and superconductivity in BaIr2P2.
AB - Detailed calculations of the electronic structure, phonons and electron-phonon
coupling of the superconducting compound BaIr2P2 were performed from first
principles. The electronic structure showed excellent agreement with the
available experimental data. The total electron-phonon coupling constant was
[Formula: see text] and the logarithmically averaged phonon frequency was
[Formula: see text] K. From the Allen-Dynes formula, with [Formula: see text],
the superconducting critical temperature was estimated to be [Formula: see text]
K, which is in excellent agreement with the experiment. These results indicate
that the electron-phonon coupling is of moderate strength and is easily capable
of supporting the observed superconductivity.
PMID- 27494505
TI - Individualized treatment to optimize eventual cognitive outcome in congenital
hypothyroidism.
AB - BACKGROUND: In congenital hypothyroidism (CH), age-specific reference ranges
(asRR) for fT4 and thyrotropine (TSH) are usually used to signal over/under
treatment. We compared the consequences of individual fT4 steady-state
concentrations (SSC's) and asRR regarding over-treatment signaling and
intelligence quotient at 11 y (IQ11) and the effect of early over-treatment with
high L-T4 dosages on IQ11. METHODS: Sixty-one patients (27 severe, 34 mild CH)
were psychologically tested at 1.8, 6, and 11 y. Development scores were related
to over-treatment in the period 0-24 mo, relative to either individual fT4SSC's
or asRR. Three groups were formed, based on severity of over/under-treatment 0-5
mo (severe, mild, and no over/under-treatment). RESULTS: FT4 and TSH asRR missed
41-50% of the over-treatment episodes and consequently 22% of the over-treated
patients, classified as such by fT4SSC's. Severe over-treatment 0-5 mo led to
lowered IQ11's and to a 5.5-fold higher risk of IQ11 < 85 than other treatment
regimes. Under-treatment had no effect on development scores. Initial L-T4
dosages >10 ug/kg resulted in a 3.7-fold higher risk of over-treatment than lower
dosages. CONCLUSIONS: Data suggest that asRR, compared to fT4SSC's, signal over
treatment insufficiently. Using fT4SSC's and avoiding over-treatment may optimize
cognitive outcome. Lowered IQ11's are usually a late complication of severe early
over-treatment.
PMID- 27494507
TI - How Do Patients and Health Workers Interact around Malaria Rapid Diagnostic
Testing, and How Are the Tests Experienced by Patients in Practice? A Qualitative
Study in Western Uganda.
AB - BACKGROUND: Successful scale-up in the use of malaria rapid diagnostic tests
(RDTs) requires that patients accept testing and treatment based on RDT results
and that healthcare providers treat according to test results. Patient-provider
communication is a key component of quality care, and leads to improved patient
satisfaction, higher adherence to treatment and better health outcomes. Voiced or
perceived patient expectations are also known to influence treatment decision
making among healthcare providers. While there has been a growth in literature on
provider practices around rapid testing for malaria, there has been little
analysis of inter-personal communication around the testing process. We
investigated how healthcare providers and patients interact and engage throughout
the diagnostic and treatment process, and how the testing service is experienced
by patients in practice. METHODS: This research was conducted alongside a larger
study which explored determinants of provider treatment decision-making following
negative RDT results in a rural district (Kibaale) in mid-western Uganda, ten
months after RDT introduction. Fifty-five patients presenting with fever were
observed during routine outpatient visits at 12 low-level public health
facilities. Observation captured communication practices relating to test
purpose, results, diagnosis and treatment. All observed patients or caregivers
were immediately followed up with in-depth interview. Analysis followed the
'framework' approach. A summative approach was also used to analyse observation
data. RESULTS: Providers failed to consistently communicate the reasons for
carrying out the test, and particularly to RDT-negative patients, a diagnostic
outcome or the meaning of test results, also leading to confusion over what the
test can detect. Patients appeared to value testing, but were frustrated by the
lack of communication on outcomes. RDT-negative patients were dissatisfied by the
absence of information on an alternative diagnosis and expressed uncertainty
around adequacy of proposed treatment. CONCLUSIONS: Poor provider communication
practices around the testing process, as well as limited inter-personal exchange
between providers and patients, impacted on patients' perceptions of their
proposed treatment. Patients have a right to health information and may be more
likely to accept and adhere to treatment when they understand their diagnosis and
treatment rationale in relation to their perceived health needs and visit
expectations.
PMID- 27494508
TI - Evaluating Clonal Expansion of HIV-Infected Cells: Optimization of PCR Strategies
to Predict Clonality.
AB - In HIV-infected individuals receiving suppressive antiretroviral therapy, the
virus persists indefinitely in a reservoir of latently infected cells. The
proliferation of these cells may contribute to the stability of the reservoir and
thus to the lifelong persistence of HIV-1 in infected individuals. Because the
HIV-1 replication process is highly error-prone, the detection of identical viral
genomes in distinct host cells provides evidence for the clonal expansion of
infected cells. We evaluated alignments of unique, near-full-length HIV-1
sequences to determine the relationship between clonality in a short region and
clonality in the full genome. Although it is common to amplify and sequence
short, subgenomic regions of the viral genome for phylogenetic analysis, we show
that sequence identity of these amplicons does not guarantee clonality across the
full viral genome. We show that although longer amplicons capture more diversity,
no subgenomic region can recapitulate the diversity of full viral genomes.
Consequently, some identical subgenomic amplicons should be expected even from
the analysis of completely unique viral genomes, and the presence of identical
amplicons alone is not proof of clonally expanded HIV-1. We present a method for
evaluating evidence of clonal expansion in the context of these findings.
PMID- 27494511
TI - Why do patients with myositis die? A retrospective analysis of a single-centre
cohort.
AB - OBJECTIVES: Causes of death in inflammatory myopathies have rarely been studied.
We have assessed a cohort of myositis patients followed in a single centre over a
37-year period, reviewing the mortality rate, causes of death and predictors of
poor prognosis. METHODS: We performed a single-centre, retrospective study on
patients aged >=16 years fulfilling 3 or 4 of the Bohan and Peter criteria,
noting their demographic data, clinical features, serology, treatment and
outcome. RESULTS: Of 97 patients identified, 74.2% were female. The mean age at
diagnosis was 40.5 years (SD 13.2). 38.1% had adult-onset dermatomyositis, 36.1%
adult-onset polymyositis and 25.8% overlap myositis. 96.9% had upper and lower
limb involvement (UL+/LL+) and 62.9% had a highest CK>=10 times the upper limit
of normal. 33% had significant infection(s). The disease course was chronic
persistent in 29.9%, relapsing and remitting in 34% and monophasic in 36.1%. All
received steroids and 92.8% other immunosuppressant(s). The median follow-up was
9 years (IQR 11.5). The estimated cumulative proportion survival at 5, 10, 15 and
20 years were 94.6%, 82.2%, 72,1% and 66.1%, respectively. 24.7% of patients
died, mostly due to infection (29.2%). In univariate analysis, lung involvement
(HR 1.78, p=0.013), infection (HR 4.18, p=0.003) and UL+/LL+ (HR 0.13, p=0.010)
were statistically significantly associated with the risk of death. In the
multivariate analysis infection (HR 3.68, p=0.009) and UL+/LL+ (HR 0.16, p=0.027)
were statistically significantly associated with survival. CONCLUSIONS: A good
long-term survival is reported. Nevertheless, careful follow-up of myositis
patients is important.
PMID- 27494510
TI - Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic
Therapy Agents via Protein Modifications.
AB - Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen
((1)O2) and superoxide radical (O2(*-)) is considered to trigger cell death
pathways associated with protein dysfunction; however, the detailed mechanisms
and direct involvement in photodynamic therapy (PDT) have not been revealed.
Herein, we report Ir(III) complexes designed for ROS generation through a
rational strategy to investigate protein modifications by ROS. The Ir(III)
complexes are effective as PDT agents at low concentrations with low-energy
irradiation (<= 1 J cm(-2)) because of the relatively high (1)O2 quantum yield (>
0.78), even with two-photon activation. Furthermore, two types of protein
modifications (protein oxidation and photo-cross-linking) involved in PDT were
characterized by mass spectrometry. These modifications were generated primarily
in the endoplasmic reticulum and mitochondria, producing a significant effect for
cancer cell death. Consequently, we present a plausible biologically applicable
PDT modality that utilizes rationally designed photoactivatable Ir(III)
complexes.
PMID- 27494512
TI - Clinical Correlates of Computationally Derived Visual Field Defect Archetypes in
Patients from a Glaucoma Clinic.
AB - PURPOSE: To assess the clinical validity of visual field (VF) archetypal
analysis, a previously developed machine learning method for decomposing any
Humphrey VF (24-2) into a weighted sum of clinically recognizable VF loss
patterns. MATERIALS AND METHODS: For each of 16 previously identified VF loss
patterns ("archetypes," denoted AT1 through AT16), we screened 30,995 reliable
VFs to select 10-20 representative patients whose VFs had the highest
decomposition coefficients for each archetype. VF global indices and patient
ocular and demographic features were extracted retrospectively. Based on
resemblances between VF archetypes and clinically observed VF patterns,
hypotheses were generated for associations between certain VF archetypes and
clinical features, such as an association between AT6 (central island,
representing severe VF loss) and large cup-to-disk ratio (CDR). Distributions of
the selected clinical features were compared between representative eyes of
certain archetypes and all other eyes using the two-tailed t-test or Fisher exact
test. RESULTS: 243 eyes from 243 patients were included, representative of AT1
through AT16. CDR was more often >= 0.7 among eyes representative of AT6 (central
island; p = 0.002), AT10 (inferior arcuate defect; p = 0.048), AT14 (superior
paracentral defect; p = 0.016), and AT16 (inferior paracentral defect; p = 0.016)
than other eyes. CDR was more often < 0.7 among eyes representative of AT1 (no
focal defect; p < 0.001) and AT2 (superior defect; p = 0.027), which was also
associated with ptosis (p < 0.001). AT12 (temporal hemianopia) was associated
with history of stroke (p = 0.022). AT11 (concentric peripheral defect) trended
toward association with trial lens correction > 6D (p = 0.069). CONCLUSIONS:
Shared clinical features between computationally derived VF archetypes and
clinically observed VF patterns support the clinical validity of VF archetypal
analysis.
PMID- 27494513
TI - MicroTrout: A comprehensive, genome-wide miRNA target prediction framework for
rainbow trout, Oncorhynchus mykiss.
AB - Rainbow trout represent an important teleost research model and aquaculture
species. As such, rainbow trout are employed in diverse areas of biological
research, including basic biological disciplines such as comparative physiology,
toxicology, and, since rainbow trout have undergone both teleost- and salmonid
specific rounds of genome duplication, molecular evolution. In recent years,
microRNAs (miRNAs, small non-protein coding RNAs) have emerged as important
posttranscriptional regulators of gene expression in animals. Given the
increasingly recognized importance of miRNAs as an additional layer in the
regulation of gene expression and hence biological function, recent efforts using
RNA- and genome sequencing approaches have resulted in the creation of several
resources for the construction of a comprehensive repertoire of rainbow trout
miRNAs and isomiRs (variant miRNA sequences that all appear to derive from the
same gene but vary in sequence due to post-transcriptional processing).
Importantly, through the recent publication of the rainbow trout genome
(Berthelot et al., 2014), mRNA 3'UTR information has become available, allowing
for the first time the genome-wide prediction of miRNA-target RNA relationships
in this species. We here report the creation of the microtrout database, a
comprehensive resource for rainbow trout miRNA and annotated 3'UTRs. The
comprehensive database was used to implement an algorithm to predict genome-wide
rainbow trout-specific miRNA-mRNA target relationships, generating an improved
predictive framework over previously published approaches. This work will serve
as a useful framework and sequence resource to experimentally address the role of
miRNAs in several research areas using the rainbow trout model, examples of which
are discussed.
PMID- 27494514
TI - The coverage of elective revascularisation procedure codes in the National
Finnish Hospital Discharge Register.
AB - INTRODUCTION: Administrative registers provide an attractive data source for real
life effectiveness studies. The validity of coronary artery disease diagnoses in
the Finnish National Hospital Discharge Register (HDR) is high but the validity
of revascularization procedure codes (percutaneous coronary intervention; PCI and
coronary artery bypass grafting; CABG) are unknown. METHODS: All elective PCIs (n
= 1771) and CABGs (n = 1819), performed at the Heart Center, Kuopio University
Hospital, Finland between years 2007 and 2014 were identified from the unit's
Special Electronic Medical Records (sEMR). Personal identity codes were used to
link these data to the HDR. Sensitivity was estimated as proportion of operations
recorded in sEMR and HDR. RESULTS: With the strictest assumption of exactly the
same intervention day in HDR and sEMR, the sensitivity for procedure codes were
84.6% for PCI and 97.1% for CABG, respectively. When a one-day difference was
allowed in the dates, the sensitivity increased to 87.6% for PCI and 98.0% for
CABG. Altogether 62.1% of elective PCIs and 69.2% of CABGs were correctly
classified as elective procedures in the HDR. CONCLUSION: The potential of the
research application of the HDR extends beyond traditionally used diagnostic
codes. One feasible application is the assessment of real-life effectiveness of
different procedures. KEY MESSAGES The majority of PCIs (87.6%) and CABGs
(98.0%), performed in the Heart Center, Kuopio University Hospital responsible
for the treatment of approximately one fifth of the Finnish population, were
captured by the Finnish National Hospital Discharge Register. However, only 62.1%
of elective PCIs and 69.2% of CABGs were correctly classified as elective
procedures in the HDR. Electivity data were missing from approximately one third
of the procedures. This study produces new information of the potential use of
HDR for real-life effectiveness studies to support evidence-based decision making
in health care.
PMID- 27494515
TI - Size of the Organic Cation Tunes the Band Gap of Colloidal Organolead Bromide
Perovskite Nanocrystals.
AB - A few approaches have been employed to tune the band gap of colloidal organic
inorganic trihalide perovskites (OTPs) nanocrystals by changing the halide anion.
However, to date, there is no report of electronic structure tuning of perovskite
NCs upon changing the organic cation. We report here, for the first time, the
room temperature colloidal synthesis of (EA)x(MA)1-xPbBr3 nanocrystals (NCs)
(where, x varies between 0 and 1) to tune the band gap of hybrid organic
inorganic lead perovskite NCs from 2.38 to 2.94 eV by varying the ratio of
ethylammonium (EA) and methylammonium (MA) cations. The tuning of band gap is
confirmed by electronic structure calculations within density functional theory,
which explains the increase in the band gap upon going toward larger "A" site
cations in APbBr3 NCs. The photoluminescence quantum yield (PLQY) of these NCs
lies between 5% to 85% and the average lifetime falls in the range 1.4 to 215 ns.
A mixture of MA cations and its higher analog EA cations provide a versatile tool
to tune the structural as well as optoelectronic properties of perovskite NCs.
PMID- 27494516
TI - Intra-articular glucocorticoid injections should not be neglected in the
remission targeted treatment of early rheumatoid arthritis: a post hoc analysis
from the NEO-RACo trial.
AB - OBJECTIVES: To study the effects of neglecting intra-articular glucocorticoid
injections (IAGCIs) into swollen joints in early rheumatoid arthritis (RA).
METHODS: Ninety-nine patients with early, DMARD naive RA were treated, aiming at
remission, with methotrexate, sulfasalazine, hydroxychloroquine, low-dose oral
prednisolone and, when needed, IAGCIs for 2 years, and randomised to receive
infliximab or placebo from weeks 4 to 26. During each of the 15 study visits,
patients were scored retrospectively 0.2-0.4 points (depending on the number of
non-injected joints) if IAGCIs to all swollen joints were not given. Patients
were divided into tertiles by their cumulative scores for neglected injections
(CSNI) over 24 months. 28-joint disease activity score (DAS28) area under the
curve (AUC) between 0-24 months, remission rates, changes in quality of life, and
radiological changes during the follow-up were assessed. Trends across tertiles
of CSNI were tested with generalised linear models. RESULTS: Higher CSNI was
associated with lower strict remission rates (p=0.005), and lower quality of life
(p=0.004) at 24 months, and higher DAS28 AUC (p<0.001) during the follow-up. At
24 months, DAS28 remission rates were 90%, 93% and 76% (p=0.081), and strict
remission rates were 74%, 77% and 39% by tertiles of CSNI. No significant
differences were observed in radiological progression (p=0.089). IAGCIs were well
tolerated. CONCLUSIONS: Neglecting IAGCIs into swollen joints is associated with
lower remission rates, higher disease activity, and lower quality of life. Hence,
IAGCIs should be used as an integral part of the targeted treatment of early RA.
PMID- 27494517
TI - Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among
Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008-2012: The
Global Enteric Multicenter Study (GEMS).
AB - OBJECTIVE: To evaluate factors associated with rotavirus diarrhea and to describe
severity of illness among children <5 years old with non-dysenteric, moderate-to
severe diarrhea (MSD) in rural western Kenya. METHODS: We analyzed data from
children <5 years old with non-dysenteric MSD enrolled as cases in the Global
Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined
as a child with >=3 loose stools in 24 hrs. and one or more of the following:
sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who
sought care at a sentinel health center within 7 days of illness onset. Rotavirus
antigens in stool samples were detected by ELISA. Demographic and clinical
information was collected at enrollment and during a single follow-up home visit
at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point
numerical scoring system adapted from the Vesikari score. We used logistic
regression to evaluate factors associated with rotavirus infection. RESULTS: From
January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD
cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive
compared with negative cases were: younger (median age, 8 vs. 13 months;
p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and
had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p
<0.013). Independent factors associated with rotavirus infection included age 0
11 months old (aOR = 5.29, 95% CI 3.14-8.89) and presenting with vomiting >=3
times/24hrs (aOR = 2.58, 95% CI [1.91-3.48]). Rotavirus was detected more
commonly in warm and dry months than in the cool and rainy months (142/691 [20%]
vs 70/673 [10%]) p<0.0001). CONCLUSIONS: Diarrhea caused by rotavirus is
associated with severe symptoms leading to hospitalization. Consistent with other
settings, infants had the greatest burden of disease.
PMID- 27494518
TI - Stereoselective Synthesis of Ezetimibe via Cross-Metathesis of Homoallylalcohols
and alpha-Methylidene-beta-Lactams.
AB - Ru-catalyzed cross-metathesis (CM) reaction between beta-arylated alpha
methylidene-beta-lactams and terminal olefins was developed. The CM reaction is
effectively catalyzed with Hoveyda-Grubbs second-generation catalyst affording
corresponding alpha-alkylidene-beta-aryl-beta-lactams in good isolated yields (41
83%) with exclusive Z-selectivity. The developed protocol was successfully
applied for stereoselective preparation of Ezetimibe, the commercial cholesterol
absorption inhibitor.
PMID- 27494519
TI - ROOT HAIR DEFECTIVE SIX-LIKE Class I Genes Promote Root Hair Development in the
Grass Brachypodium distachyon.
AB - Genes encoding ROOT HAIR DEFECTIVE SIX-LIKE (RSL) class I basic helix loop helix
proteins are expressed in future root hair cells of the Arabidopsis thaliana root
meristem where they positively regulate root hair cell development. Here we show
that there are three RSL class I protein coding genes in the Brachypodium
distachyon genome, BdRSL1, BdRSL2 and BdRSL3, and each is expressed in developing
root hair cells after the asymmetric cell division that forms root hair cells and
hairless epidermal cells. Expression of BdRSL class I genes is sufficient for
root hair cell development: ectopic overexpression of any of the three RSL class
I genes induces the development of root hairs in every cell of the root
epidermis. Expression of BdRSL class I genes in root hairless Arabidopsis
thaliana root hair defective 6 (Atrhd6) Atrsl1 double mutants, devoid of RSL
class I function, restores root hair development indicating that the function of
these proteins has been conserved. However, neither AtRSL nor BdRSL class I genes
is sufficient for root hair development in A. thaliana. These data demonstrate
that the spatial pattern of class I RSL activity can account for the pattern of
root hair cell differentiation in B. distachyon. However, the spatial pattern of
class I RSL activity cannot account for the spatial pattern of root hair cells in
A. thaliana. Taken together these data indicate that that the functions of RSL
class I proteins have been conserved among most angiosperms-monocots and eudicots
despite the dramatically different patterns of root hair cell development.
PMID- 27494520
TI - Dopamine Receptor Gene DRD4 7-Repeat Allele X Maternal Sensitivity Interaction on
Child Externalizing Behavior Problems: Independent Replication of Effects at 18
Months.
AB - The DRD4 VNTR has been associated with child behavior problems in interaction
with maternal insensitivity in European and American cohorts of preschoolers,
with the 7-repeat (7R) allele associated with greater problems. We sought to
replicate and expand these findings by examining effects on reports of child
behavior problems at 18 months. A 63 family sample with data for observed
maternal sensitivity ratings, DRD4 VNTR genotype, and maternal report of child
behavior problems at 18-months was used in this preliminary analysis. Maternal
sensitivity was measured at 6-months of age using laboratory observational
measures (free-play and a teaching task). Maternal report of toddler behavior was
obtained at 18-months via the standard Child Behavior Checklist, and infant
genotype on the DRD4 VNTR was obtained using PCR. Infants carrying the DRD4 7R
allele showed greater effects of maternal insensitivity than non-carriers for
behavioral problems at 18-months. We replicated previous findings of association
of infant DRD4 x maternal sensitivity interactions with child Externalizing
problems in the European-ancestry sample (N = 42) in a median split of maternal
sensitivity (p = .00011, eta2 = .329) and in regression analyses controlling for
maternal age, maternal depression, and child gender in European ancestry (B =
3.4, SE 1.33, p = .01) and the total sample (B = -2.2, SE 1.02, p = .02).
Exploratory analyses also found evidence of DRD4 x maternal sensitivity
interaction with the CBCL ADHD scale. These findings replicate in an independent
cohort DRD4 x maternal insensitivity interaction effect on child externalizing
behavior problems at 18 months, further supporting the role of the DRD4 genotype
in differential sensitivity to parenting.
PMID- 27494521
TI - Characterization of Cells Isolated from Genetic and Trauma-Induced Heterotopic
Ossification.
AB - Heterotopic ossification (HO) is the pathologic formation of bone separate from
the normal skeleton. Although several models exist for studying HO, an
understanding of the common in vitro properties of cells isolated from these
models is lacking. We studied three separate animal models of HO including two
models of trauma-induced HO and one model of genetic HO, and human HO specimens,
to characterize the properties of cells derived from tissue containing pre-and
mature ectopic bone in relation to analogous mesenchymal cell populations or
osteoblasts obtained from normal muscle tissue. We found that when cultured in
vitro, cells isolated from the trauma sites in two distinct models exhibited
increased osteogenic differentiation when compared to cells isolated from
uninjured controls. Furthermore, osteoblasts isolated from heterotopic bone in a
genetic model of HO also exhibited increased osteogenic differentiation when
compared with normal osteoblasts. Finally, osteoblasts derived from mature
heterotopic bone obtained from human patients exhibited increased osteogenic
differentiation when compared with normal bone from the same patients. These
findings demonstrate that across models, cells derived from tissues forming
heterotopic ossification exhibit increased osteogenic differentiation when
compared with either normal tissues or osteoblasts. These cell types can be used
in the future for in vitro investigations for drug screening purposes.
PMID- 27494522
TI - Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell
Anemia.
AB - Pain is a hallmark feature of sickle cell anemia (SCA) but management of chronic
as well as acute pain remains a major challenge. Mouse models of SCA are
essential to examine the mechanisms of pain and develop novel therapeutics. To
facilitate this effort, we compared humanized homozygous BERK and Townes sickle
mice for the effect of gender and age on pain behaviors. Similar to previously
characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal,
and deep tissue hyperalgesia with increasing age. Female Townes sickle mice
demonstrate more hyperalgesia compared to males similar to that reported for BERK
mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia
increased further after hypoxia/reoxygenation (H/R) treatment in Townes sickle
mice. Together, these data show BERK sickle mice exhibit a significantly greater
degree of hyperalgesia for all behavioral measures as compared to gender- and age
matched Townes sickle mice. However, the genetically distinct "knock-in" strategy
of human alpha and beta transgene insertion in Townes mice as compared to BERK
mice, may provide relative advantage for further genetic manipulations to examine
specific mechanisms of pain.
PMID- 27494523
TI - Importance of Hypervariable Region 2 for Stability and Affinity of a Shark Single
Domain Antibody Specific for Ebola Virus Nucleoprotein.
AB - Single-domain antibodies derived from the unique New Antigen Receptor found in
sharks have numerous potential applications, ranging from diagnostic reagents to
therapeutics. Shark-derived single-domain antibodies possess the same
characteristic ability to refold after heat denaturation found in single-domain
antibodies derived from camelid heavy-chain-only antibodies. Recently, two shark
derived single-domain antibodies specific for the nucleoprotein of Ebola virus
were described. Our evaluation confirmed their high affinity for the
nucleoprotein, but found their melting temperatures to be low relative to most
single-domain antibodies. Our first approach towards improving their stability
was grafting antigen-binding regions (complementarity determining regions) of one
of these single-domain antibodies onto a high melting temperature shark single
domain antibody. This resulted in two variants: one that displayed excellent
affinity with a low melting temperature, while the other had poor affinity but a
higher melting temperature. These new proteins, however, differed in only 3 amino
acids within the complementarity determining region 2 sequence. In shark single
domain antibodies, the complementarity determining region 2 is often referred to
as hypervariable region 2, as this segment of the antibody domain is truncated
compared to the sequence in camelid single-domain antibodies and conventional
heavy chain variable domains. To elucidate which of the three amino acids or
combinations thereof were responsible for the affinity and stability we made the
6 double and single point mutants that covered the intermediates between these
two clones. We found a single amino acid change that achieved a 10 degrees C
higher melting temperature while maintaining sub nM affinity. This research gives
insights into the impact of the shark sdAb hypervariable 2 region on both
stability and affinity.
PMID- 27494524
TI - Why Do Drivers Use Mobile Phones While Driving? The Contribution of Compensatory
Beliefs.
AB - The current study is the first to investigate the contribution of compensatory
beliefs (i.e., the belief that the negative effects of an unsafe behavior can be
"neutralized" by engaging in another safe behavior; e.g., "I can use a mobile
phone now because I will slow down ") on drivers' mobile phone use while driving.
The effects of drivers' personal characteristics on compensatory beliefs, mobile
phone use and self-regulatory behaviors were also examined. A series of questions
were administered to drivers, which included (1) personal measures, (2) scales
that measured compensatory beliefs generally in substance use and with regard to
driving safety, and (3) questions to measure drivers' previous primary mobile
phone usage and corresponding self-regulatory actions. Overall, drivers reported
a low likelihood of compensatory beliefs, prior mobile phone use, and a strong
frequency of self-regulatory behaviors. Respondents who had a higher tendency
toward compensatory beliefs reported more incidents or crash involvement caused
by making or answering calls and sending or reading messages. The findings
provide strong support for the contribution of compensatory beliefs in predicting
mobile phone usage in the context of driving. Compensatory beliefs can explain
41% and 43% of the variance in the active activities of making calls and
texting/sending messages compared with 18% and 31% of the variance in the passive
activities of answering calls and reading messages. Among the regression models
for predicting self-regulatory behaviors at the tactical or operational level,
compensatory beliefs emerge as significant predictors only in predicting shorter
conversations while on a call. The findings and limitations of the current study
are discussed.
PMID- 27494525
TI - The plant alkaloid chelerythrine binds to chromatin, alters H3K9Ac and modulates
global gene expression.
AB - Chelerythrine (CHL), a plant alkaloid, possesses antimicrobial, anti
inflammatory, and antitumor properties. Although CHL influences several key
signal transduction pathways, its ability to interact directly with nucleoprotein
complex chromatin, in eukaryotic cells has so far not been looked into. Here we
have demonstrated its association with hierarchically assembled chromatin
components, viz. long chromatin, chromatosome, nucleosome, chromosomal DNA, and
histone H3 and the consequent effect on chromatin structure. CHL was found to
repress acetylation at H3K9. It is more target-specific in terms of gene
expression alteration and less cytotoxic compared to its structural analog
sanguinarine.
PMID- 27494526
TI - Young People Smokers' Reactions on Peer Influence Not to Smoke.
AB - BACKGROUND: Peers exert influence not to smoke but little is yet known on how
this affects young people's behavior and cognitions. OBJECTIVES: This
experimental study investigates the impact of two types of peer influence not to
smoke on the verbalized attitudes and responses of daily-smoking young people.
METHODS: Two conditions were conducted: 1) a peer confederate stating three times
that s/he had quit smoking and was glad to have done so (covert peer influence);
2) a peer confederate making similar statements, but urging to quit smoking
(overt peer influence). The participant performed a music task with the peer in
order to disguise the true nature of the experiment. Thirty-one daily-smoking
young people (16-24 years) participated; 44 responses in the overt and 34
responses in the covert condition were analyzed in a discourse analysis. RESULTS:
The participants in the covert condition were more elaborative about smoking,
i.e., taking an active role in a dialogue about the experiences of the peer or
the participant in quitting smoking while in the overt condition participants
showed more passive resistance, i.e., not showing an intention to follow the
advice but avoid causing the peer embarrassment or discomfort. Open resistance,
i.e., demonstration of being well-informed and indicating the redundancy of the
advice, does not significantly differ in these two conditions but occurs, for
both, primarily at the third discouragement. CONCLUSIONS: Overt and frequent
discouragement seems to be less effective in stimulating young people to take an
active role in the dialogue with their peers about smoking.
PMID- 27494527
TI - Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic
Stroke Patients: A Sub-Group Analysis of SMART.
AB - BACKGROUND: Although increasing evidence suggests that hyperglycemia following
acute stroke adversely affects clinical outcome, whether the association between
glycaemia and functional outcome varies between stroke patients with?without pre
diagnosed diabetes remains controversial. We aimed to investigate the
relationship between the fasting blood glucose (FBG) and the 6-month functional
outcome in a subgroup of SMART cohort and further to assess whether this
association varied based on the status of pre-diagnosed diabetes. METHODS: Data
of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics)
enrolled from SMART cohort were analyzed. Functional outcome at 6-month post
stroke was measured by modified Rankin Scale (mRS) and categorized as favorable
(mRS:0-2) or poor (mRS:3-5). Binary logistic regression model, adjusting for age,
gender, educational level, history of hypertension and stroke, baseline NIHSS and
treatment group, was used in the whole cohort to evaluate the association between
admission FBG and functional outcome. Stratified logistic regression analyses
were further performed based on the presence/absence of pre-diabetes history.
RESULTS: In the whole cohort, multivariable logistical regression showed that
poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07
1.37), p = 0.002), older age (OR1.64 (95% CI1.38-1.94), p<0.001), higher NIHSS
(OR2.90 (95%CI 2.52-3.33), p<0.001) and hypertension (OR1.42 (95%CI 1.13-1.98), p
= 0.04). Stratified logistical regression analysis showed that the association
between FBG and functional outcome remained significant only in patients without
pre-diagnosed diabetes (OR1.26 (95%CI 1.03-1.55), p = 0.023), but not in those
with premorbid diagnosis of diabetes (p = 0.885). CONCLUSION: The present results
demonstrate a significant association between elevated FBG after stroke and poor
functional outcome in patients without pre-diagnosed diabetes, but not in
diabetics. This finding confirms the importance of glycemic control during acute
phase of ischemic stroke especially in patients without pre-diagnosed diabetes.
Further investigation for developing optimal strategies to control blood glucose
level in hyperglycemic setting is therefore of great importance. TRIAL
REGISTRATION: ClinicalTrials.gov NCT00664846.
PMID- 27494528
TI - Moderators of Treatment Effects of a Video-Based Cognitive-Behavioral Therapy for
Insomnia Comorbid With Cancer.
AB - PURPOSE: To assess the moderating role of demographic and clinical variables on
the efficacy of a video-based cognitive behavioral therapy for insomnia (VCBT-I)
among breast cancer patients. PATIENTS AND METHODS: As part of a randomized
controlled trial, 80 women received VCBT-I. RESULTS: Patients with a more
advanced breast cancer were less likely to show reductions on the Insomnia
Severity Index (ISI) and increased sleep efficiency at posttreatment. Patients
using an antidepressant medication showed a larger reduction of ISI scores and a
higher rate of insomnia remission. Remission of insomnia was also significantly
more likely in individuals with a higher annual income. When using a multivariate
binary classification tree analysis, the best and unique predictor of insomnia
remission was having a less severe baseline ISI score. CONCLUSION: Although
efficacious in general, VCBT-I does not appear to be an optimal format for
everybody.
PMID- 27494530
TI - Benefits and Limitations of Polymorphic and Amorphous Forms of Active
Pharmaceutical Ingredients.
AB - Active pharmaceutical ingredients (APIs) can exist in different polymorphic forms
as well as in amorphous state. Polymorphic and amorphous forms of APIs can differ
in physicochemical properties which in turn can significantly influence their
therapeutic safety and effectiveness of the treatment. This review focuses on
benefits and limitations of polymorphic and amorphous forms of APIs used in
preformulation and formulation studies. Authors present their work on safety
precautions for the use of polymorphic and amorphous forms of APIs, analytical
techniques used for their identification as well as methods of their preparation
especially in regard to limitations of labile APIs.
PMID- 27494529
TI - Novel Roles of Epoxyeicosanoids in Regulating Cardiac Mitochondria.
AB - Maintenance of a healthy pool of mitochondria is important for the function and
survival of terminally differentiated cells such as cardiomyocytes.
Epoxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of
arachidonic acid by cytochrome P450 epoxygenases. We have previously shown that
EETs trigger a protective response limiting mitochondrial dysfunction and
reducing cellular death. The aim of this study was to investigate whether EET
mediated effects influence mitochondrial quality in HL-1 cardiac cells during
starvation. HL-1 cells were subjected to serum- and amino acid free conditions
for 24h. We employed a dual-acting synthetic analog UA-8 (13-(3
propylureido)tridec-8-enoic acid), possessing both EET-mimetic and soluble
epoxide hydrolase (sEH) inhibitory properties, or 14,15-EET as model EET
molecules. We demonstrated that EET-mediated events significantly improved
mitochondrial function as assessed by preservation of the ADP/ATP ratio and
oxidative respiratory capacity. Starvation induced mitochondrial hyperfusion
observed in control cells was attenuated by UA-8. However, EET-mediated events
did not affect the expression of mitochondrial dynamic proteins Fis1, DRP-1 or
Mfn2. Rather we observed increased levels of OPA-1 oligomers and increased
mitochondrial cristae density, which correlated with the preserved mitochondrial
function. Increased DNA binding activity of pCREB and Nrf1/2 and increased SIRT1
activity together with elevated mitochondrial proteins suggest EET-mediated
events led to preserved mitobiogenesis. Thus, we provide new evidence for EET
mediated events that preserve a healthier pool of mitochondria in cardiac cells
following starvation-induced stress.
PMID- 27494531
TI - Predictors of Diet-Induced Weight Loss in Overweight Adults with Type 2 Diabetes.
AB - AIMS: A very low calorie diet improves the metabolic regulation of obesity
related type 2 diabetes, but not for all patients, which leads to frustration in
patients and professionals alike. The aim of this study was to develop a
prediction model of diet-induced weight loss in type 2 diabetes. METHODS: 192
patients with type 2 diabetes and BMI>27 kg/m2 from the outpatient diabetes
clinic of the Erasmus Medical Center underwent an 8-week very low calorie diet.
Baseline demographic, psychological and physiological parameters were measured
and the C-index was calculated of the model with the largest explained variance
of relative weight loss using backward linear regression analysis. The model was
internally validated using bootstrapping techniques. RESULTS: Weight loss after
the diet was 7.8+/-4.6 kg (95%CI 7.2-8.5; p<0.001) and was independently
associated with the baseline variables fasting glucose (B = -0.33 (95%CI -0.49,
0.18), p = 0.001), anxiety (HADS; B = -0.22 (95%CI -0.34, -0.11), p = 0.001),
numb feeling in extremities (B = 1.86 (95%CI 0.85, 2.87), p = 0.002), insulin
dose (B = 0.01 (95%CI 0.00, 0.02), p = 0.014) and waist-to-hip ratio (B = 6.79
(95%CI 2.10, 11.78), p = 0.003). This model explained 25% of the variance in
weight loss. The C-index of this model to predict successful (>=5%) weight loss
was 0.74 (95%CI 0.67-0.82), with a sensitivity of 0.93 (95% CI 0.89-0.97) and
specificity of 0.29 (95% CI 0.16-0.42). When only the obese T2D patients (BMI>=30
kg/m2; n = 181) were considered, age also contributed to the model (B = 0.06
(95%CI 0.02, 0.11), p = 0.008), whereas waist-to-hip ratio did not. CONCLUSIONS:
Diet-induced weight loss in overweight adults with T2D was predicted by five
baseline parameters, which were predominantly diabetes related. However, failure
seems difficult to predict. We propose to test this prediction model in future
prospective diet intervention studies in patients with type 2 diabetes.
PMID- 27494532
TI - Prospects for subunit vaccines: Technology advances resulting in efficacious
antigens requires matching advances in early clinical trial investment.
AB - With the continued march of antimicrobial resistance, a renewed impetus for
better vaccines has been heralded. Identification of potent subunit vaccines has
been greatly facilitated by recent developments in reverse vaccinology and
proteomics strategies. There are a range of antimicrobial resistant bacterial
pathogens that could be targeted by potent vaccine antigens identified within the
coming years. However, cost is a significant hurdle in progressing lead antigen
candidates to clinical trials. In order for novel vaccine technologies to realize
their clinical potential, there is a requirement to improve investment and
incentives to expedite the development of vaccines that are apparently
efficacious in preclinical trials.
PMID- 27494533
TI - Chronic exposure to endosulfan induces inflammation in murine colon via beta
catenin expression and IL-6 production.
AB - Endosulfan (ENDO) is a widely used organochlorine (OC) pesticide and persistent
organo-pollutant. Epidemiological studies have shown that high levels of OC
exposure were related to colorectal cancer (CRC) incidence. The objectives of the
present study were to evaluate histological changes in the colon, as well as in
in situ expression of beta-catenin and P-selectin, and serum levels of select pro
inflammatory cytokines in mice administered ENDO; there is a relationship between
increased serum IL-6 and P-selectin levels in CRC patients and aberrant beta
catenin signaling is important in initiation/maintenance of most CRCs. Mice were
exposed to ENDO (at dose < LD50) orally once a week for up to 24 weeks, and
monitored (inclusive) for a total of 42 weeks. The experiment was comprised of
three groups, one that did not receive ENDO (olive oil vehicle), one administered
2 mg ENDO/kg/week and a positive control (for induction of CRC) given a weekly 20
mg 1,2-dimethylhydrazine (DMH)/kg injection. The results indicated that oral
administration of ENDO provoked moderate inflammation starting at six weeks, and
severe colonic inflammation with an appearance of dysplastic formations (aberrant
crypts) in mice treated with ENDO (or DMH) for 12 weeks or longer. Serum IL-6
levels significantly increased starting at six weeks and rose to a peak of 15
fold higher than in controls at 42 weeks; TNFalpha levels likewise significantly
increased, with a later peak (~four-fold higher than controls) at 30-42 weeks.
Immunohistochemical analysis of the colon also showed that expression of beta
catenin and P-selectin increased with length of exposure to ENDO. Taken together,
the results indicate that continued repeated oral exposure to ENDO induces
increased expression of beta-catenin and P-selectin, inflammation in the colon,
and, ultimately, local tissue dysplasia.
PMID- 27494534
TI - Boswellia serrata Protects Against Glutamate-Induced Oxidative Stress and
Apoptosis in PC12 and N2a Cells.
AB - This study was designed to investigate whether the extract from Boswellia serrata
oleo-gum resin (BSE) can protect against glutamate-induced oxidative damage and
cytotoxicity in PC12 and N2a cell lines. Using a simple and reliable reverse
phase high-performance liquid chromatography (HPLC), the amount of 3-acetyl-11
keto-beta-boswellic acid (AKBA) in the BSE was found to be 18.5% w/w. The results
confirmed that BSE and AKBA, at concentrations as high as 100 MUg/mL or 10 MUM,
respectively, caused no significant cytotoxicity or apoptotic cell death. Co- and
pretreatment with BSE (25-100 MUg/mL) or AKBA (5 MUM) restored the viability of
PC12 and N2a cells under glutamate toxicity (8 mM). Treatment with BSE and AKBA
also attenuated the toxic effects of glutamate on intracellular reactive oxygen
species, lipid peroxidation, superoxide dismutase activity, and oxidative DNA
damage compared with the untreated glutamate-injured cells. Furthermore, BSE and
AKBA decreased the apoptotic cell population in the sub-G1 region and the rate of
both early and late-stage apoptosis induced by glutamate in the cells. Our data
suggest that the protective effects of Boswellia extract and AKBA against
glutamate toxicity in PC12 and N2a cells may be mediated through the amelioration
of the oxidative stress and the resultant apoptosis.
PMID- 27494535
TI - Colloidal preparation and electrocatalytic hydrogen production of MoS2 and WS2
nanosheets with controllable lateral sizes and layer numbers.
AB - Although layered transition metal dichalcogenide (TMD) nanosheets have attracted
great attention due to their unique properties, it still remains challenge to
develop a facile strategy for the precise control of the lateral sizes and layer
numbers of TMD nanosheets. In this study, we demonstrate a solution-phase
synthetic protocol to prepare colloidal MS2 (M = Mo, W) nanosheets which possess
extremely small lateral dimensions from 15 to 40 nm and well-controlled odd
numbers of layers, such as 1, 3, and 5 layers, as characterized by transmission
electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The
size- and layer-dependence of the optical properties of colloidal MS2 (M = Mo, W)
nanosheets are revealed by Raman and absorption spectra for the first time. These
colloidal nanosheets, especially the single-layer ones, possess a large number of
edge sites that serve as active sites for the hydrogen evolution reaction (HER).
The catalysts exhibit a small HER overpotential and low Tafel slope of
approximately 100 mV and 52 mV per decade for MoS2, and 80 mV and 46 mV per
decade for WS2, respectively. Importantly, these products show enhanced stability
after 500 potential cycles, and the current density remains almost unchanged
during the test.
PMID- 27494536
TI - Residential greenness and blood lipids in children: A longitudinal analysis in
GINIplus and LISAplus.
AB - INTRODUCTION: There is some evidence of decreased cardiovascular disease (CVD)
mortality and morbidity among adults residing in greener places. Among others,
blood lipids are well established risk factors for CVD. In our previous study, we
observed the inverse association between greenness and blood pressure in 10-year
old children. In the current study, we investigated whether there is also a link
between residential greenness and blood lipids in 10- and 15-year-old children.
METHODS: Complete data on blood lipids (total cholesterol, HDL, LDL and
triglyceride), residential greenness (NDVI in 100-m, 300- and 500-m buffers
around residences) and confounders were available for 1,552 participants at 10
and 15 years of age, residing in two study areas of two German birth cohorts -
GINIplus and LISAplus. Longitudinal associations between NDVI and blood lipids
were assessed by generalized estimation equations. RESULTS: No associations were
observed between residential greenness in any of the chosen buffers and blood
lipids in children (e.g., change in blood lipids per interquartile increase in
NDVI in 100-m buffer for total cholesterol and LDL: means ratio=1.00 (95%
confidence interval: 0.99-1.01), for triglyceride: 0.98 (0.96-1.00)). No area- or
sex-varying effects were evident. Change of the residence between 10 and 15 years
also did not yield any consistent associations. CONCLUSIONS: There is no evidence
of an association between greenness and blood lipids in 10- and 15-years old
children.
PMID- 27494538
TI - Are nails a valuable non-invasive alternative for estimating human exposure to
phthalate esters?
AB - Most human biomonitoring studies conducted in the past year for assessing the
human exposure to phthalate esters (PEs) employed measurements of PE metabolites
in urine. Although urine is recognized as a valuable non-invasive matrix, it has
also limitations regarding the short time window for exposure. Therefore, in this
pilot feasibility study we aimed to assess the human exposure to seven PE
metabolites (including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5
oxohexyl) phthalate (5-oxo-MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (5-OH
MEHP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monoethyl
phthalate (MEP) and mono-benzyl phthalate (MBzP)) using human nails. Paired nails
and urine samples from the same individuals were used for comparison. Median
levels of specific PE metabolites measured in nails and in spot urine of twenty
Belgian individuals ranged from [Ln(H2O)9]3+ +
[An(BTP)3]3+ exchange reaction energies were evaluated, revealing Eu <-> Am and
Gd <-> Cm reactions to favor the An species. Detailed QTAIM analysis of Eu, Gd,
Am, and Cm complexes revealed increased covalent character in M-O and M-N bonds
when M = An, with this increase being more pronounced in the BTP complexes. This
therefore implies a small electronic contribution to An-N bond stability and the
experimentally observed selectivity of the BTP ligand for Am and Cm over
lanthanides.
PMID- 27494550
TI - Eu(2+)-Activated Alkaline-Earth Halophosphates, M5(PO4)3X:Eu(2+) (M = Ca, Sr, Ba;
X = F, Cl, Br) for NUV-LEDs: Site-Selective Crystal Field Effect.
AB - Eu(2+)-activated M5(PO4)3X (M = Ca, Sr, Ba; X = F, Cl, Br) compounds providing
different alkaline-earth metal and halide ions were successfully synthesized and
characterized. The emission peak maxima of the M5(PO4)3Cl:Eu(2+) (M = Ca, Sr, Ba)
compounds were blue-shifted from Ca to Ba (454 nm for Ca, 444 nm for Sr, and 434
nm for Ba), and those of the Sr5(PO4)3X:Eu(2+) (X = F, Cl, Br) compounds were red
shifted along the series of halides, F -> Cl -> Br (437 nm for F, 444 nm for Cl,
and 448 nm for Br). The site selectivity and occupancy of the activator ions
(Eu(2+)) in the M5(PO4)3X:Eu(2+) (M = Ca, Sr, Ba; X = F, Cl, Br) crystal lattices
were estimated based on theoretical calculation of the 5d -> 4f transition
energies of Eu(2+) using LCAO. In combination with the photoluminescence
measurements and theoretical calculation, it was elucidated that the Eu(2+) ions
preferably enter the fully oxygen-coordinated sites in the M5(PO4)3X:Eu(2+) (M =
Ca, Sr, Ba; X = F, Cl, Br) compounds. This trend can be well explained by
"Pauling's rules". These compounds may provide a platform for modeling a new
phosphor and application in the solid-state lighting field.
PMID- 27494551
TI - Covalent Nitrogen Doping and Compressive Strain in MoS2 by Remote N2 Plasma
Exposure.
AB - Controllable doping of two-dimensional materials is highly desired for ideal
device performance in both hetero- and p-n homojunctions. Herein, we propose an
effective strategy for doping of MoS2 with nitrogen through a remote N2 plasma
surface treatment. By monitoring the surface chemistry of MoS2 upon N2 plasma
exposure using in situ X-ray photoelectron spectroscopy, we identified the
presence of covalently bonded nitrogen in MoS2, where substitution of the
chalcogen sulfur by nitrogen is determined as the doping mechanism. Furthermore,
the electrical characterization demonstrates that p-type doping of MoS2 is
achieved by nitrogen doping, which is in agreement with theoretical predictions.
Notably, we found that the presence of nitrogen can induce compressive strain in
the MoS2 structure, which represents the first evidence of strain induced by
substitutional doping in a transition metal dichalcogenide material. Finally, our
first principle calculations support the experimental demonstration of such
strain, and a correlation between nitrogen doping concentration and compressive
strain in MoS2 is elucidated.
PMID- 27494552
TI - Support Persons' Perceptions of Giving Vocational Rehabilitation Support to
Clients With Acquired Brain Injury in Sweden.
AB - The aim of this article is to explore the perception of being a support person
for clients with acquired brain injury undergoing vocational rehabilitation. Nine
support persons, identified by clients with brain injury, were interviewed.
Interviews were analyzed using qualitative content analysis, resulting in 3
themes for assisting the client: commitment, adaptation, and cooperation. Within
each theme, multiple dimensions were identified, reflecting the complexity of
vocational rehabilitation following acquired brain injury. Commitment built on
social relations is linked to sustainability of support. The included support
persons' role was especially valuable in contexts where adaptation and
cooperation were required.
PMID- 27494553
TI - Graphene Quantum Dot-MnO2 Nanosheet Based Optical Sensing Platform: A Sensitive
Fluorescence "Turn Off-On" Nanosensor for Glutathione Detection and Intracellular
Imaging.
AB - Glutathione (GSH) monitoring has attracted extensive attention because it serves
a vital role in human pathologies. Herein, a convenient fluorescence "turn off
on" nanosensor based on graphene quantum dots (GQDs)-manganese dioxide (MnO2)
nanosheet has been designed for selective detection of GSH in living cells. The
fluorescence intensity of GQDs can be quenched by MnO2 nanosheets via a
fluorescence resonance energy transfer. However, GSH can reduce MnO2 nanosheets
to Mn(2+) cations and release GQDs, causing sufficient recovery of fluorescent
signal. The MnO2 nanosheets serve as both fluorescence nanoquencher and GSH
recognizer in the sensing platform. The sensing platform displayed a sensitive
response to GSH in the range of 0.5-10 MUmol L(-1), with a detection limit of 150
nmol L(-1). Furthermore, the chemical response of the GQDs-MnO2 nanoprobe
exhibits high selectivity toward GSH over other electrolytes and biomolecules.
Most importantly, the promising platform was successfully applied in monitoring
the intracellular GSH in living cells, indicating its great potential to be used
in disease diagnosis. Meanwhile, this GQDs-MnO2 platform is also generalizable
and can be easily expanded to the detection and imaging of other reactive species
in living cells.
PMID- 27494554
TI - Attaching Accessory Devices to the Replisome.
AB - Evidence mounts, via two studies published in Molecular Cell (Villa et al. 2016;
Samora et al. 2016), that Ctf4 recruits to the replisome various factors that
play diverse roles in chromosome duplication, by acting as an interaction hub.
PMID- 27494555
TI - Who Put the "A" in ATP? Generation of ATP from ADP-Ribose in the Nucleus for
Hormone-Dependent Gene Regulation.
AB - In a recent issue of Science, Wright et al. (2016) describe a pathway for the
synthesis of nuclear ATP, leading from NAD(+) to poly(ADP-ribose) to ADP-ribose
to ATP, which supports the activity of ATP-dependent chromatin remodeling enzymes
during hormone-dependent transcription.
PMID- 27494556
TI - Who Is in the Driver's Seat: Tracing Cancer Genes Using CRISPR-Barcoding.
AB - Intratumor heterogeneity is thought to be the driving force of tumor evolution
and therapy resistance. Yet tools to study these processes are limited. In this
issue, Guernet et al. (2016) devised clustered regularly interspaced short
palindromic repeats (CRISPR)-barcoding to functionally annotate specific
mutations and study clonal evolution in heterogeneous cell populations.
PMID- 27494559
TI - K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and
mRNA Decapping.
PMID- 27494557
TI - Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity.
AB - Advances in the development of delivery, repair, and specificity strategies for
the CRISPR-Cas9 genome engineering toolbox are helping researchers understand
gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also
holds enormous therapeutic potential for the treatment of genetic disorders by
directly correcting disease-causing mutations. Although the Cas9 protein has been
shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity
is rapidly progressing, with marked improvements in guide RNA selection, protein
and guide engineering, novel enzymes, and off-target detection methods. We review
important challenges and breakthroughs in the field as a comprehensive practical
guide to interested users of genome editing technologies, highlighting key tools
and strategies for optimizing specificity. The genome editing community should
now strive to standardize such methods for measuring and reporting off-target
activity, while keeping in mind that the goal for specificity should be continued
improvement and vigilance.
PMID- 27494558
TI - Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-beta
Catenin Signaling.
AB - The poly(ADP-ribose) polymerase (PARP) Tankyrase (TNKS and TNKS2) is paramount to
Wnt-beta-catenin signaling and a promising therapeutic target in Wnt-dependent
cancers. The pool of active beta-catenin is normally limited by destruction
complexes, whose assembly depends on the polymeric master scaffolding protein
AXIN. Tankyrase, which poly(ADP-ribosyl)ates and thereby destabilizes AXIN, also
can polymerize, but the relevance of these polymers has remained unclear. We
report crystal structures of the polymerizing TNKS and TNKS2 sterile alpha motif
(SAM) domains, revealing versatile head-to-tail interactions. Biochemical studies
informed by these structures demonstrate that polymerization is required for
Tankyrase to drive beta-catenin-dependent transcription. We show that the
polymeric state supports PARP activity and allows Tankyrase to effectively access
destruction complexes through enabling avidity-dependent AXIN binding. This study
provides an example for regulated signal transduction in non-membrane-enclosed
compartments (signalosomes), and it points to novel potential strategies to
inhibit Tankyrase function in oncogenic Wnt signaling.
PMID- 27494560
TI - Linker-Mediated Self-Assembly Dynamics of Charged Nanoparticles.
AB - Using in situ liquid cell transmission electron microscopy (TEM), we visualized a
stepwise self-assembly of surfactant-coated and hydrated gold nanoparticles (NPs)
into linear chains or branched networks. The NP binding is facilitated by linker
molecules, ethylenediammonium, which form hydrogen bonds with surfactant
molecules of neighboring NPs. The observed spacing between bound neighboring NPs,
~15 A, matches the combined length of two surfactants and one linker molecule.
Molecular dynamics simulations reveal that for lower concentrations of linkers,
NPs with charged surfactants cannot be fully neutralized by strongly binding
divalent linkers, so that NPs carry higher effective charges and tend to form
chains, due to poor screening. The highly polar NP surfaces polarize and partly
immobilize nearby water molecules, which promotes NPs binding. The presented
experimental and theoretical approach allows for detail observation and
explanation of self-assembly processes in colloidal nanosystems.
PMID- 27494562
TI - Sphingosine-1-phosphate receptor: a novel therapeutic target in ulcerative
colitis.
PMID- 27494563
TI - The use of spent mushroom compost to enhance the ability of Atriplex halimus to
phytoremediate contaminated mine soils.
AB - The mushroom cultivation industry produces a huge amount of spent mushroom
compost (SMC), a wide world agricultural organic waste which causes serious
environmental problems. However, this cheap organic waste could be useful in the
remediation of contaminated soils. The aim of this work was to assess the
potential of SMC in combination with the native shrub Atriplex halimus, to
phytoremediate two mine soils contaminated with Cd, Pb and Cu. Firstly, to
minimize metal availability in the soil, the optimal doses of SMC were
determined. Secondly, a phytoremediation assay in greenhouse conditions was
carried out to test the effects of A. halimus in combination with SMC at
different doses. The results showed the ability of SMC to reduce soil acidity,
the mobility of the metals and the enhancement of A. halimus growth. SMC promoted
metal immobilization in the root of A. halimus and decreased the translocation
from the roots to the shoots. The combination of SMC amendment and A. halimus
produced phytostabilization of the metals in the mine soils assayed. In
conclusion, SMC represents an adequate organic solid waste which in combination
with A. halimus can reduce the adverse impact caused by the high mobility of
metals in acid mine soils.
PMID- 27494564
TI - Confidence-Competence Mismatch and Reasons for Failure of Non-Medical Tourniquet
Users.
AB - OBJECTIVE: Tourniquet application is a lifesaving skill taught worldwide in first
aid bleeding control courses. We observed performance among non-medical users of
tourniquets in their confidence, competence, and reasons for failure. METHODS:
179 Israeli military recruits without prior medical training underwent their
standard first aid course where they learned Combat Application Tourniquet (CAT;
Composite Resources, Rock Hill, SC, USA) use. After course completion, they self
reported confidence in tourniquet use. User performance was assessed 7-14 days
later using a HapMedTM mannequin that assessed time, pressure, and blood loss.
Competent performance required in aggregate: 1) use with pressure of 200 mmHg or
more, 2) hemorrhage volume of less than 638 mL, and 3) correct placement of the
tourniquet. For failed performance, a reason for failure was reported
independently by both the user and an expert observer. RESULTS: 45 of 179 user
performances (25%) were competent. Users who reported high confidence had only a
slightly higher chance of achieving competence in tourniquet application (r =
0.17, p = 0.022). The most common reason for failure was excess slack in the
CAT's strap (experts 55%, users 39%), and too few turns of the windlass (23% and
31%, respectively) was the second most common reason. Expert and user evaluations
had poor agreement (kappa = 0.44, 95% CI 0.32-0.56). CONCLUSION: The most common
reason for failed use of tourniquets among non-medical users was excess slack in
the tourniquet strap. Users self-evaluated their performance inaccurately and
demonstrated a confidence-competence mismatch. These pitfalls in performance may
help tourniquet instructors improve training of caregivers.
PMID- 27494565
TI - Effects of growth temperature and carbon dioxide enrichment on soybean seed
components at different stages of development.
AB - Soybean plants were grown to maturity in controlled environment chambers and at
the onset of flowering three temperature treatments were imposed that provided
optimum [28/24 degrees C], low [22/18 degrees C] or high [36/32 degrees C]
chamber air temperatures. In addition, plants were treated continuously with
either 400 or 800 MUmol mol-1 CO2. Seeds were harvested at 42, 53, 69 and 95 days
after planting (i.e., final maturity). This study quantified 51 metabolites in
developing soybean seeds, plus total lipids and proteins were measured at
maturity. About 80% of measured soluble carbohydrates, amines and organic acids
decreased to low levels in mature seeds, although important exceptions were
raffinose, ribose/arabinose, citrate and all eight fatty acids. This suggested
that the metabolism of young seeds supported lipid and protein synthesis. A total
of 35 and 9 metabolites differed among temperature and CO2 treatments,
respectively, and treatment effects were predominately observed on the first and
second samplings. However, shikimate, pinitol and oleate were increased by high
temperature treatments in mature seeds. The above results indicated that CO2
enrichment primarily altered metabolite levels during the initial stages of seed
development and this was likely due to enhanced photosynthate formation in
leaves.
PMID- 27494566
TI - Dual contribution of surface charge and protein-binding affinity to the
cytotoxicity of polystyrene nanoparticles in nonphagocytic A549 cells and
phagocytic THP-1 cells.
AB - Knowledge that links the physicochemical properties of nanoparticles (NP) to
their toxicity is key to evaluating and understanding mechanisms underlying
toxicity and developing appropriate testing methods for NP; however, this is
currently limited since only a small set of NP have been used, with typically
poor control of their physical properties. In this study, eight types of
polystyrene NP (PLNP) were synthesized with different functional groups, but all
based on an identical core. In vitro cell-based assays were performed to
determine the influence of changes in physicochemical properties, such as charge,
hydrodynamic size, and protein binding potential, in relation to NP-mediated
toxicity. The PLNP were incubated with nonphagocytic A549 cells or phagocytic
differentiated THP-1 cells for 4 h with/without fetal bovine serum (FBS),
followed by incubation for 20 h in FBS-supplemented medium with/without a washing
step, to assess cell-type specificity and impact of protein corona formation. The
effect of surface charge on cytotoxicity differed between A549 cells and THP-1
cells. In nonphagocytic A549 cells, the zeta potential of PLNP exhibited a
negative correlation with cytotoxicity, partly due to the level of coronated
protein that might affect cellular uptake. In phagocytic THP-1 cells, the zeta
potential of PLNP showed a positive correlation with cytotoxicity but coronated
protein levels displayed no marked association with cytotoxicity, owing to the
professional uptake efficacy of phagocytic cells. The consistency of our data
with THP-1 cells with the surface charge paradigm in nanotoxicology suggests that
phagocytic cells are the predominant targets for lung inflammatory reactions
induced by PLNP.
PMID- 27494567
TI - Ultrafast Time-Resolved Emission and Absorption Spectra of meso-Pyridyl
Porphyrins upon Soret Band Excitation Studied by Fluorescence Up-Conversion and
Transient Absorption Spectroscopy.
AB - A comprehensive study of ultrafast molecular relaxation processes of isomeric
meso-(pyridyl) porphyrins (TpyPs) has been carried out by using femtosecond time
resolved emission and absorption spectroscopic techniques upon pumping at 400 nm,
Soret band (B band or S2), in 4:1 dichloromethane (DCM) and tetrahydrofuran (THF)
solvent mixture. By combined studies of fluorescence up-conversion, time
correlated single photon counting, and transient absorption spectroscopic
techniques, a complete model with different microscopic rate constants associated
with elementary processes involved in electronic manifolds has been reported.
Besides, a distinct coherent nuclear wave packet motion in Qy state is observed
at low-frequency mode, ca. 26 cm(-1) region. Fluorescence up-conversion studies
constitute ultrafast time-resolved emission spectra (TRES) over the whole
emission range (430-710 nm) starting from S2 state to Qx state via Qy state.
Careful analysis of time profiles of up-converted signals at different emission
wavelengths helps to reveal detail molecular dynamics. The observed lifetimes are
as indicated: A very fast decay component with 80 +/- 20 fs observed at ~435 nm
is assigned to the lifetime of S2 (B) state, whereas being a rise component in
the region of between 550 and 710 nm emission wavelength pertaining to Qy and Qx
states, it is attributed to very fast internal conversion (IC) occurring from B
> Qy and B -> Qx as well. Two distinct components of Qy emission decay with ~200
300 fs and ~1-1.5 ps time constants are due to intramolecular vibrational
redistribution (IVR) induced by solute-solvent inelastic collisions and
vibrational redistribution induced by solute-solvent elastic collision,
respectively. The weighted average of these two decay components is assigned as
the characteristic lifetime of Qy, and it ranges between 0.3 and 0.5 ps. An
additional ~20 +/- 2 ps rise component is observed in Qx emission, and it is
assigned to the formation time of thermally equilibrated Qx state by vibrational
cooling/relaxations of excess energy within solvent. This relaxed Qx state decays
to ground as well as triplet state by 7-8 ns time scale. The femtosecond
transient absorption studies of TpyPs in three different excitations at S2 (400
nm), Qy (515 nm), and Qx (590 nm) along with extensive global and target model
analysis of TA data exclusively generate the true spectra of each excited
species/state with their respective lifetimes along with microscopic rate
constants associated with each state. The following five exponential components
with lifetime values of 65-70 fs, ~0.3-0.5 ps, ~20 +/- 2 ps, ~7 +/- 1 ns, and 1-2
MUs are observed which are associated with S2, Qy, hot Qx, thermally relaxed Qx,
and lowest triplet (T1) states, respectively, when excited at S2, and four (Qy,
hot Qx, thermally relaxed Qx, and lowest triplet (T1) states) and three (hot Qx,
thermally relaxed Qx, and lowest triplet (T1) states) states are obtained when
excited at 515 nm (Qy) and 590 nm (Qx), respectively, as expected. The TA results
parallel the fluorescence up-conversion studies, and both the results not only
compliment each other but also unveil the ultrafast internal conversion from S2
to Qy, S2 to Qx, and Qy to Qx for all three isomers in a similar fashion with
nearly equal characteristic decay times.
PMID- 27494568
TI - Views and experience of communication when receiving a serious mental health
diagnosis: satisfaction levels, communication preferences, and acceptability of
the SPIKES protocol.
AB - BACKGROUND: There is limited research investigating how information about a
mental health diagnosis is discussed and received. AIMS: To measure community
based service users' satisfaction and preferences toward receiving news of a
serious mental health diagnosis and to assess the acceptability of a diagnostic
communication protocol (SPIKES: Setting; Perception; Invitation; Knowledge;
Empathy; Summarizing). METHOD: A survey was conducted with 101 participants.
RESULTS: Participants rated the methods clinicians use to facilitate diagnostic
discussions are highly important; however, they were not wholly satisfied with
their experience. Higher satisfaction was reported if participants were provided
with information in a face-to-face meeting (p < 0.001), and if they received
supplementary support at the time of diagnosis from additional health
professionals rather than only a sole practitioner (p < 0.001). The SPIKES
protocol was rated as highly acceptable, with Empathy being rated as the most
important feature. CONCLUSIONS: This research indicates there were specific areas
of communication practices which can be improved within mental health service
provision, as a gap existed between participants' desire for support and their
experience. Strategies outlined in the SPIKES protocol, and others such as
addressing stigma concerns, may prove useful in development of clinician training
and service improvement.
PMID- 27494569
TI - Birth Satisfaction Scale/Birth Satisfaction Scale-Revised (BSS/BSS-R): A large
scale United States planned home birth and birth centre survey.
AB - OBJECTIVE: to explore the prevalence of birth satisfaction for childbearing women
planning to birth in their home or birth centers in the United States. Examining
differences in birth satisfaction of the home and birth centers; and those who
birthed in a hospital using the 30-item Birth Satisfaction Scale (BSS) and the 10
item Birth Satisfaction Scale-Revised (BSS-R). STUDY DESIGN: a quantitative
survey using the BSS and BSS-R were employed. Additional demographic data were
collected using electronic linkages (QualtricsTM). PARTICIPANTS: a convenience
sample of childbearing women (n=2229) who had planned to birth in their home or
birth center from the US (United States) participated. Participants were
recruited via professional and personal contacts, primarily their midwives.
RESULTS: the total 30-item BSS score mean was 128.98 (SD 16.92) and the 10-item
BSS-R mean score was 31.94 (SD 6.75). Sub-scale mean scores quantified the
quality of care provision, women's personal attributes, and stress experienced
during labour. Satisfaction was higher for women with vaginal births compared
with caesareans deliveries. In addition, satisfaction was higher for women who
had both planned to deliver in a home or a birth centre, and who had actually
delivered in a home or a birth center. KEY CONCLUSIONS: total and subscale birth
satisfaction scores were positive and high for the overall sample IMPLICATIONS
FOR PRACTICE: the BSS and the BSS-R provide a robust tool to quantify women's
experiences of childbirth between variables such as birth types, birth settings
and providers.
PMID- 27494561
TI - Image-guided ultrasound phased arrays are a disruptive technology for non
invasive therapy.
AB - Focused ultrasound offers a non-invasive way of depositing acoustic energy deep
into the body, which can be harnessed for a broad spectrum of therapeutic
purposes, including tissue ablation, the targeting of therapeutic agents, and
stem cell delivery. Phased array transducers enable electronic control over the
beam geometry and direction, and can be tailored to provide optimal energy
deposition patterns for a given therapeutic application. Their use in combination
with modern medical imaging for therapy guidance allows precise targeting, online
monitoring, and post-treatment evaluation of the ultrasound-mediated bioeffects.
In the past there have been some technical obstacles hindering the construction
of large aperture, high-power, densely-populated phased arrays and, as a result,
they have not been fully exploited for therapy delivery to date. However, recent
research has made the construction of such arrays feasible, and it is expected
that their continued development will both greatly improve the safety and
efficacy of existing ultrasound therapies as well as enable treatments that are
not currently possible with existing technology. This review will summarize the
basic principles, current statures, and future potential of image-guided
ultrasound phased arrays for therapy.
PMID- 27494571
TI - The value of mortality risk reductions. Pure altruism - a confounder?
AB - This paper examines public valuations of mortality risk reductions. We set up a
theoretical framework that allows for altruistic preferences, and subsequently
test theoretical predictions through the design of a discrete choice experiment.
By varying the tax scenario (uniform versus individual tax), the experimental
design allows us to verify whether pure altruistic preferences are present and
the underlying causes. We find evidence of negative pure altruism. Under a
coercive uniform tax system respondents lower their willingness to pay possibly
to ensure that they are not forcing others to pay at a level that corresponds to
their own - higher - valuations. This hypothesis is supported by the observation
that respondents perceive other individuals' valuations to be lower than their
own. Our results suggest that public valuations of mortality risk reductions may
underestimate the true societal value because respondents are considering other
individuals' welfare, and wrongfully perceive other people's valuations to be
low.
PMID- 27494570
TI - A multicentre, open-label, randomised phase III study comparing a new
levonorgestrel intrauterine contraceptive system (LNG-IUS 8) with combined oral
contraception in young women of reproductive age.
AB - OBJECTIVES: To compare user satisfaction and adverse events (AEs) with a
levonorgestrel intrauterine system (LNG-IUS 8; average levonorgestrel release
rate approximately 8 MUg/24 h over the first year [total content 13.5 mg]) and a
30 MUg ethinyl estradiol/3 mg drospirenone (EE/DRSP) combined oral contraceptive
(COC) in a population of young women. METHODS: Nulliparous and parous women (aged
18-29 years) with regular menstrual cycles (21-35 days) were randomised to LNG
IUS 8 or EE/DRSP for 18 months. The primary endpoint was the overall user
satisfaction rate at month 18/end of study visit. RESULTS: Overall, 279 women
were randomised to LNG-IUS 8 with attempted placement and 281 women were
randomised to EE/DRSP and took >=1 pill; the mean age was 23.7 and 23.9 years,
and 77.4% and 73.3% were nulliparous, respectively. At month 18/end of study,
82.1% and 81.9% of women, respectively, reported being 'very satisfied' or
'satisfied' with their treatment; however, significantly more LNG-IUS 8 users
reported a preference to continue their treatment post-study (66.2% vs 48.8%; p =
0.0001). There were two pregnancies (one ectopic pregnancy, one spontaneous
abortion) reported in the LNG-IUS 8 group and six (three live births, two
spontaneous abortions, one induced abortion) in the EE/DRSP group. CONCLUSIONS:
LNG-IUS 8 and EE/DRSP were associated with similarly high user satisfaction
rates. However, LNG-IUS 8 users were significantly more likely to prefer to
continue their contraceptive method post-study, indicating that a levonorgestrel
intrauterine system is an appealing contraceptive option for young women.
PMID- 27494572
TI - Therapist interventions and client ambivalence in two cases of narrative therapy
for depression.
AB - AIM: We understand ambivalence as a cycle of opposing expressions by two internal
voices. The emergence of a suppressed voice produces an innovative moment (IM),
challenging the dominant voice, which represents the client's problematic self
narrative. The emergence of the IM is opposed by the dominant voice, leading to a
return to the problematic self-narrative. This study analyzed therapist and
client responses to each other in episodes of ambivalence. METHOD: The
therapeutic collaboration coding system (TCCS) assesses whether and how the
therapeutic dyad is working within the therapeutic zone of proximal development
(TZPD) by examining client responses to therapist interventions. We applied the
TCCS to episodes in which a good- and a poor-outcome client in narrative therapy
expressed ambivalence. RESULTS: In both the good- and poor-outcome cases, the
therapist responded to the emergence of ambivalence similarly, balancing
challenging and supporting. The good-outcome case responded at the developmental
level proposed by the therapist when challenged, while the poor-outcome case
lagged behind the level proposed. DISCUSSION: This supports the theoretical
explanation that the therapist did not match client's developmental level in the
poor-outcome case, working beyond the client's current TZPD and contributing to
the maintenance of ambivalence.
PMID- 27494573
TI - An Exploratory Study Investigating How Adults with Intellectual Disabilities
Perform on the Visual Association Test (VAT).
AB - BACKGROUND: Neuropsychological tests of memory are believed to offer the greatest
sensitivity at identifying people at the risk of developing dementia. There is a
paucity of standardized and appropriate neuropsychological assessments of memory
for adults with an intellectual disability. This study examines how adults with
an intellectual disability perform on the Visual Association Test (VAT). METHODS:
Forty participants (18-45 years) with intellectual disability, without a
diagnosis of dementia, completed the VAT and subtests of the CAMCOG-DS.
Correlational analysis of the test variables was carried out. RESULTS: All
participants performed well on the VAT irrespective of age, gender or IQ. No
significant correlations were found between the VAT and the subtests of the
CAMCOG-DS. CONCLUSIONS: The VAT was found to be an easy and quick test to use
with people with intellectual disability and all participants scored above
'floor' level.
PMID- 27494575
TI - Challenging Problems in Rhinoplasty.
PMID- 27494574
TI - Atypical VZV Retinitis in a Patient with Good Syndrome.
AB - PURPOSE: To describe atypical varicella zoster virus (VZV) retinitis in a patient
with Good syndrome. METHODS: A 63-year-old patient with Good syndrome presented
with bilateral necrotizing retinitis starting from the posterior pole. He had a
history of thymoma status post thymectomy 4 years previously, left-sided
sinusitis, and recent pulmonary aspergillosis. Qualitative PCR was performed on
aqueous fluid. RESULTS: Immunological investigations revealed reduced levels of
CD4+ T cells and immunoglobulins. Qualitative PCR was positive for VZV and
negative for cytomegalovirus, herpes simplex virus (HSV)-1, and HSV-2. The
patient was treated with oral valacyclovir and three courses of immunoglobulin
supplementation. The atypical retinitis showed improvement after therapy.
CONCLUSION: Good syndrome should be considered in a patient with opportunistic
infections and history of thymoma in the absence of human immunodeficiency virus.
Atypical retinitis can occur in patients with Good syndrome and quantitative PCR
is important for accurate diagnosis.
PMID- 27494576
TI - Columellar Aesthetics in Open Rhinoplasty.
AB - Detailed descriptions of the ideals of columellar aesthetics and nostril shape
are conspicuously lacking from the medical literature. Achieving an aesthetic
nasal base is critical to an optimal rhinoplasty result. Deviations in the
columella and variations in its width and height lead to distortion of nostril
shape and frequently compromise function. Six types of columellar disproportion
are presented with detailed explanations of how to treat each. By properly
recognizing and addressing columellar deformities, the surgeon can optimize both
the aesthetic and functional results that are achieved.
PMID- 27494577
TI - Nasal Soft-Tissue Triangle Deformities.
AB - The soft-tissue triangle is one of the least areas attended to in rhinoplasty.
Any postoperative retraction, notching, or asymmetries of soft triangles can
seriously affect the rhinoplasty outcome. A good understanding of the risk
factors predisposing to soft triangle deformities is necessary to prevent such
problems. The commonest risk factors in our study were the wide vertical domal
angle between the lateral and intermediate crura, and the increased length of
intermediate crus. Two types of soft triangle grafts were described to prevent
and treat soft triangle deformities. The used soft triangle grafts resulted in an
excellent long-term aesthetic and functional improvement.
PMID- 27494578
TI - Refining the Nasal Dorsum with Free Diced Cartilage.
AB - Refining the nasal dorsum has become a major challenge in modern rhinoplasty as
irregularities of the nasal dorsum account for a significant number of revision
surgeries. In our department, free diced cartilage is now routinely applied for
smoothening of the nasal dorsum. In this retrospective study, the outcomes with
regard to irregularities or contour deficits of the nasal dorsum of 431
rhinoplasty cases operated by a single surgeon between July 2013 and June 2015,
using free diced cartilage, are compared with 327 cases operated by the same
surgeon between January 2007 and December 2008, before the introduction of the
free diced cartilage technique. A decrease in early revision surgeries (i.e.,
revision within the 2-year period evaluated) due to dorsal irregularities or
contour deficits is seen. Being a quick, easy, and highly cost-effective
procedure, we feel that free diced cartilage is currently the ideal technique for
refinements of the nasal dorsum.
PMID- 27494579
TI - Septal Surgery Challenges in Rhinoplasty.
AB - During rhinoplasty, the most stressful areas of the nasal cartilaginous septum
are at the key area and anterior nasal spine. A stable fixation of the caudal
septum to respond to these stresses is of utmost importance. The prerequisite for
a successful fixation is a well-prepared recipient bed for caudal septum and
suture fixation. The bed can be opened by using scissors, osteotome, or powered
instrumentation. Simple or multiple sutures passing from the bone and/or
surrounding soft tissues are used for fixation. At the key area, if a complete
separation of the L-strut occurs, it should be sutured to nasal bones and upper
lateral cartilages. The septum should be supported by splinting spreader grafts
to increase stability. To prevent dorsal irregularities, a dorsal onlay
camouflage graft should be used. The best way is to take cautions to prevent such
a mishap. That is why a dorsal segment of 12 to 15 mm should be preserved, at
least at the key area, and part of the mucoperichondrium should stay attached to
the septum.
PMID- 27494580
TI - Rhinoplasty: The Asymmetric Crooked Nose-An Overview.
AB - There are three reasons why the asymmetric crooked nose is one of the greatest
challenges in rhinoplasty surgery. First, the complexity of the problem is not
appreciated by the patient nor understood by the surgeon. Patients often see the
obvious deviation of the nose, but not the distinct differences between the right
and left sides. Surgeons fail to understand and to emphasize to the patient that
each component of the nose is asymmetric. Second, these deformities can be
improved, but rarely made flawless. For this reason, patients are told that the
result will be all "-er words," better, straighter, cuter, but no "t-words,"
there is no perfect nor straight. Most surgeons fail to realize that these cases
represent asymmetric noses on asymmetric faces with the variable of ipsilateral
and contralateral deviations. Third, these cases demand a wide range of
sophisticated surgical techniques, some of which have a minimal margin of error.
This article offers an in-depth look at analysis, preoperative planning, and
surgical techniques available for dealing with the asymmetric crooked nose.
PMID- 27494581
TI - Options for Middle Vault and Dorsum Restoration after Hump Removal in Primary
Rhinoplasty.
AB - Prevention of unfavorable sequelae following humpectomy in reduction rhinoplasty
by restoration of the middle nasal vault complex today has become imperative in
the majority of patients with perhaps the exception of small humps. In general,
the techniques used for preservation and reconstruction of these important
anatomical structures can be divided into two main categories: spreader graft and
spreader flap techniques. Oversimplified spreader graft techniques require donor
cartilage, whereas spreader flap techniques use the excess height of the medial
portion of the upper lateral cartilages in patients with a cartilaginous hump. In
principle, both donor cartilage and preserved upper lateral cartilages usually
are positioned along both sides of the dorsal septum to provide natural and
harmonious contours as well as to avoid functional impairment (valve collapse).
However, the considerable number of publications on this topic attests to
existing downsides of both surgical principles. To overcome these shortcomings,
we illustrate additional modifications in the application of spreader grafts as
well as spreader flaps. However, the main goal of this article is to provide an
algorithm helping to decide which technique is best suited to meet the
requirements of each individual patient.
PMID- 27494582
TI - The Articulated Alar Rim Graft: Reengineering the Conventional Alar Rim Graft for
Improved Contour and Support.
AB - Surgical refinement of the wide nasal tip is challenging. Achieving an
attractive, slender, and functional tip complex without destabilizing the lower
nasal sidewall or deforming the contracture-prone alar rim is a formidable task.
Excisional refinement techniques that rely upon incremental weakening of wide
lower lateral cartilages (LLC) often destabilize the tip complex and distort tip
contour. Initial destabilization of the LLC is usually further exacerbated by
"shrink-wrap" contracture, which often leads to progressive cephalic retraction
of the alar margin. The result is a misshapen tip complex accentuated by a
conspicuous and highly objectionable nostril deformity that is often very
difficult to treat. The "articulated" alar rim graft (AARG) is a modification of
the conventional rim graft that improves treatment of secondary alar rim
deformities, including postsurgical alar retraction (PSAR). Unlike the
conventional alar rim graft, the AARG is sutured to the underlying tip complex to
provide direct stationary support to the alar margin, thereby enhancing graft
efficacy. When used in conjunction with a well-designed septal extension graft
(SEG) to stabilize the central tip complex, lateral crural tensioning (LCT) to
tighten the lower nasal sidewalls and minimize soft-tissue laxity, and lysis of
scar adhesions to unfurl the retracted and scarred nasal lining, the AARG can
eliminate PSAR in a majority of patients. The AARG is also highly effective for
prophylaxis against alar retraction and in the treatment of most other contour
abnormalities involving the alar margin. Moreover, the AARG requires
comparatively little graft material, and complications are rare. We present a
retrospective series of 47 consecutive patients treated with the triad of AARG,
SEG, and LCT for prophylaxis and/or treatment of alar rim deformities. Outcomes
were favorable in nearly all patients, and no complications were observed. We
conclude the AARG is a simple and effective method for avoiding and correcting
most alar rim deformities.
PMID- 27494583
TI - Pollybeak Deformity in Middle Eastern Rhinoplasty: Prevention and Treatment.
AB - The pollybeak deformity is one of the commonest causes of revision rhinoplasty.
The Middle Eastern nose has certain criteria that predispose to the development
of pollybeak deformity. The aim of this study is to detect the factors
contributing to the development of pollybeak deformity in the Middle Eastern nose
and methods used to prevent as well as to treat such deformity. Out of the 1,160
revision patients included in this study, 720 (62%) patients had a pollybeak
deformity. The commonest contributing factors included underprojected tip with
poor support in 490 (68%) patients, excessive supratip scarring in 259 (36%)
patients, overresected bony dorsum in 202 (28%) patients, and high anterior
septal angle in 173 (24%) patients. The methods used by the authors to treat the
pollybeak deformity are described, along with the local steroid injection
protocol used to guard against the recurrence of pollybeak deformity.
PMID- 27494584
TI - Modern Rhinoplasty: Is There a Place for the Closed Approach?
AB - Rhinoplasty is one of the most commonly performed cosmetic surgeries and, in many
cases, an elective procedure. Therefore, it is crucial to assess the functional
and aesthetic issues of the patient accurately and devise the proper surgical
strategy most beneficial to the patient. Modern rhinoplasties can be approached
by two distinct techniques: the open technique or the closed, endonasal
technique. While most rhinosurgeons today prefer the open procedure due its
superior access to the nasal scaffold and overview over the surgical field in
particular, we highlight in this article techniques and benefits of endonasal
rhinoplasty and critically discuss situations where such an approach yields
superior results. Each rhinoplasty procedure, with its inherent strengths and
weaknesses, has to be matched with a given nasal condition and the desired
results to offer the maximum benefit to the patient. Therefore, each rhinosurgeon
should be knowledgeable and trained in the endonasal technique. Open rhinosurgery
is not always necessary and may even be disadvantageous in some cases.
PMID- 27494585
TI - Revision Rhinoplasty: What Can We Learn from Error Patterns? An Analysis of
Revision Surgery.
AB - Of the many challenges in rhinoplasty, achieving a satisfactory outcome at the
first operation is important. There are multiple reasons for secondary surgery,
and generally revisions can be broadly classified into minor (often one area of
deficit) or a total redo. Understanding the common technical reasons for failure
in primary surgery by analyzing the deformities has resulted in various error
patterns emerging. Understanding these patterns means we can modify techniques in
primary surgery to reduce the incidence of revision. This article describes our
prospective revision rhinoplasty experience over 5 and then 2 years, highlighting
the main error patterns encountered. We also describe a stepwise analysis of four
frequently encountered key problem areas alongside techniques to address them and
offer pearls to help prevent further revision. Comparison of two cohorts of
patients from a teaching hospital setting and private practice with the same
operating surgeon indicates an increasing tendency to the open approach for
revisions. The re-revision rates for these groups are 15.7 and 9%, respectively.
Revision rhinoplasty is a difficult operation to perform to the satisfaction of
both the surgeon and the patient. Understanding the common technical reasons for
failure in primary surgery by fully analyzing the deformities means we can modify
techniques in primary surgery to reduce the incidence of revision.
PMID- 27494586
TI - The Tongue-in-Groove Technique in Primary and Revision Rhinoplasty.
AB - The tongue-in-groove (TIG) is a conservative but powerful surgical suture
technique to control tip rotation and projection, to set an appropriate alar
columellar relationship, to straighten a caudal septal deviation, and to
stabilize the nasal base. TIG is suitable in primary and most revision cases and
is easily combined with other surgical techniques. Seventeen years after its
popularization, the TIG technique is embedded in modern-day rhinoplasty
literature and teaching material. This article describes indications and
considerations during external primary and revision rhinoplasty, based on
clinical experience and the available literature.
PMID- 27494587
TI - Contemporary Issues in the Open Management of Subcondylar Fractures of the
Mandible.
AB - Subcondylar fractures encompass a large portion of mandible fractures. Owing to
their proximity to the temporomandibular joint and difficulty achieving surgical
exposure, treatment of these fractures has been challenging and highly debated
throughout the literature. While no one modality is the accepted gold standard,
there are multiple options for addressing these fractures that can yield
satisfying results for both patient and surgeon alike. A thorough literature
review was conducted using PubMed, analyzing articles in the past 15 years for
relevance to the subject matter. Various search terms were used to glean
information regarding closed treatment, open treatment, and the risks and
benefits of the different surgical approaches involved. The articles were
reviewed by all of the authors for applicability and quality of data provided. A
total of 50 articles were selected for inclusion in the current study. The open
management of subcondylar fractures encompasses a vast array of techniques. While
some surgeons advocate closed treatment in some circumstances, open treatment
affords numerous advantages with the advent of multiple access modalities. There
is no single superior method, and as such, the craniofacial surgeon should have a
comprehensive understanding of options so as to select the appropriate option
that is individualized to the patient. A clear understanding of fracture
biomechanics balanced with patient expectations and operative safety allows for
the surgeon to make a sound decision for treatment.
PMID- 27494588
TI - Evaluation of the Effect of Bosentan-Mediated Endothelin Receptor Blockade on
Flap Survival in Rats: An Experimental Study.
AB - Local skin flaps are important tools for performing plastic surgery. Skin flaps
are used for closure of defects after tumor excision or in tissue losses after
trauma. However, problems associated with these flaps are commonly encountered,
particularly in areas of marginal necrosis. Bosentan is a vasodilator that exerts
its effect through endothelin receptor blockade, and has been shown to prevent
ischemic tissue damage. However, no reports have addressed the effect of bosentan
on skin flaps. The aim of the study was to investigate the effects of bosentan,
which may be applied clinically to promote survival of ischemic skin flaps. A
modified McFarlane flap was elevated in the dorsum of 20 Albino Wistar rats with
a width-to-length ratio of 3 to 10 cm, respectively, with the caudal base.
Perioperatively, 0.9% of physiologic NaCl and injectable distilled water of
identical volume were injected into rats in Group 1 (n = 10), and 5 mg/kg
bosentan was injected intraperitoneally into rats in Group 2 (n = 10). All of the
rats were followed up for 7 days postoperatively. The surviving parts of the
flaps were measured at the end of day 7. Acute and chronic inflammation, amount
of granulation tissue, fibroblast maturation, amount of collagen, and amounts of
reepithelialization and neovascularization present in the ischemic zones of the
distal parts of the flaps were evaluated histopathologically, and results were
compared statistically. The mean flap survivals were 61.1% in Group 1 and 91.1%
in Group 2; the percentage of the surviving flap area in Group 2 was higher than
that in Group 1 (p < 0.005). In both groups, there was significantly less acute
inflammation in the ischemic zones in Group 2 than in Group 1 (p < 0.005). No
significant difference was found in the amounts of chronic inflammation and
granulation tissue between the two groups (p > 0.005). Fibroblast maturation,
amount of collagen, and amounts of reepithelialization and neovascularization
investigated in Group 2 were statistically significantly higher than those in
Group 1 (p < 0.005). We believe that bosentan may be used prophylactically to
increase survival in risky skin flaps because it decreases ischemic necrosis
distal to skin flaps, thus exerting favorable effects on flap survival.
PMID- 27494589
TI - Effects of Deferoxamine on Fat Graft Survival.
AB - The most important problem in fat transplantation is the unpredictable rates of
resorption. Deferoxamine (DFO) is an iron-chelating agent with many useful
functions including stimulating angiogenesis and antioxidant nature. The purpose
of the study is to evaluate the effects of DFO on fat graft viability in rat
model. A total of 24 Wistar rats were divided into three groups and 0.5 g of the
left inguinal fat pad was extracted. In control group, fat grafts were implanted
to the parascapular area without performing any procedure. In sham group, they
were implanted in 0.2 mL saline solution followed by serial saline injections for
1 month. In the study group, fat grafts were implanted in 0.2 mL saline solution
and 300 mg DFO followed by serial DFO injections for 1 month. At the
postoperative second month, fat grafts were taken back and sent for
histopathologic examination. The weight measurements of biopsy specimens in the
study group demonstrated significantly higher than in the other two groups.
Inflammation and fibrosis rates were also found to be significantly higher in the
study group compared with the other groups; however, no significant difference in
the apoptosis rates was detected between the groups. Fat grafts enriched with DFO
showed significant increase in fatty tissue content in the study group compared
with the control and sham groups. DFO increases the fat graft survival in rats
and it may be a useful addition in autologous fat grafting procedures to increase
fat graft viability and obtain maximal long-term durability.
PMID- 27494590
TI - Nasofrontal Angle and Nasal Dorsal Aesthetics: A Quantitative Investigation of
Idealized and Normative Values.
AB - This study is a quantitative evaluation of the influence of the lower component
of the nasofrontal angle on perceived attractiveness and threshold values of
desire for rhinoplasty. The nasofrontal angle of an idealized silhouette male
Caucasian profile image was altered incrementally between 106 and 148 degrees.
Images were rated on a Likert scale by pretreatment patients (n = 75), laypeople
(n = 75), and clinicians (n = 35). The results demonstrated that a nasofrontal
angle of approximately 130 degrees is ideal, corresponding to a lower component
of 60 degrees, with a range of 127 to 142 degrees deemed acceptable. Angles above
or below this range are perceived as unattractive, and anything outside the range
of 118 to 145 degrees is deemed very unattractive. Reduced nasofrontal angles,
simulating a nasal hump deformity, of less than 115 degrees were deemed the least
attractive. In terms of threshold values of desire for surgery, for all groups a
threshold value of 148 degrees indicated a preference for surgery: for patients,
the threshold value was 121 degrees or less; for lay people, the threshold value
was 124 degrees or less; and similarly for clinicians, the threshold value was
118 degrees or less. Clinicians were the least critical, and patients appeared to
be less critical than lay people. This stresses the importance of using patients
as observers, as well as laypeople and clinicians, in facial attractiveness
research. From the results of this study, it is recommended that in rhinoplasty
planning, the range of normal variability of the nasofrontal angle, in terms of
observer acceptance, is taken into account as well as the threshold values of
desire for surgery.
PMID- 27494591
TI - The Pi Graft for Correction of Severe Saddle Nose Deformity.
AB - Saddle nose deformity is challenging because there is both aesthetic and
functional compromise, and high rates of recurrence have been reported.
Autologous costal cartilage is the widely preferred medium for reconstruction,
but there may be room for improvement in the configuration of the cartilage
struts. The pi graft is stabilized at two points, proximally and distally,
distinguishing it from the traditional L-strut. Indications include severe (Types
III and IV) saddle nose deformity with collapse of the mid-vault, and recurrence
after prior reconstruction. Costal cartilage is harvested and three struts are
crafted to make the foundation layer: a dorsal strut, caudal strut, and mid-vault
strut. An aesthetic layer is composed of a carefully crafted dorsal graft and tip
graft. Three men and 11 women were treated from 2013 to 2015 using this method
for severe saddle nose deformity. Aesthetic and functional outcomes were
evaluated. Patients were followed up for 12 months (range, 8-14 months). There
was no recurrence of deformity or warping of the aesthetic or foundation layers.
All patients were guided to anticipate refinement of the tip at 3 months to ease
the burden on the skin envelope in stage I, but only five patients (35.7%) opted
for it, as the remaining patients were satisfied with their appearance. The pi
graft is a composite reconstructive method that is designed to minimize warping
and recurrence of the saddle nose deformity. This method was successful in this
series, although objective comparisons with traditional methods were not made.
PMID- 27494592
TI - A New Perspective for Spreader Graft Use in Severely Deviated Septum: Is Septal
Continuity an Obligation for a Stable and Straight Nasal Septum?
AB - Severe septal deviation is a challenging deformity usually treated using
aggressive surgical methods, and extracorporeal septoplasty (ECS) is a commonly
used method for this issue. However, this method has severe risks and
complications such as the recurrent deformity or nasal saddling. In this article,
we present an alternative solution to ECS procedure for the correction of severe
septal deviation. Sixteen patients with severe c- or s-shaped septal deviation
with a mean age of 26.5 years were included in the study. The entire deviated
part of the septal cartilage was resected as a vertical block creating a full
thickness defect between the most cranial and caudal parts of the septal
cartilage. After that, two spreader grafts were placed bilaterally facilitating
the septal integrity and leaving the full-thickness septal defect unchanged. The
surgical results were evaluated using the preoperative and postoperative facial
photographs and patient satisfaction was determined using nine relevant questions
of DAS-59 scale. The only complication observed in the follow-up period of 19
months was hanging columella deformity which was corrected at the postoperative
first year. The mean length of the resected septal segment was 12.4 mm. The mean
length of the resultant septal cartilage defect after the vertical resection was
5.9 mm. The mean length of the placed spreader grafts was 25.6 mm. The comparison
of the preoperative and postoperative photographs showed significant improvement
of the nasal contour and considerable correction of the septal deviation. The
statistical evaluation of the answers given to the questions of the DAS-59 scale
clearly demonstrates that a significant degree of patient satisfaction was
achieved. Severe septal deviation may be successfully corrected by full-thickness
resection of the deviated part and reconstruction with bilateral spreader grafts
with a low risk of postoperative complications.
PMID- 27494593
TI - Successful Nose Replantation Using Leeches for Venous Draining.
PMID- 27494594
TI - Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy.
AB - BACKGROUND: Congenital heart defects may be environmentally related, but the
association with elevated ambient temperature has received little attention.
OBJECTIVES: We studied the relationship between outdoor heat during the first
trimester of pregnancy and risk of congenital heart defects. METHODS: We carried
out a retrospective cohort study of 704,209 fetuses between 2 and 8 weeks
postconception from April to September in Quebec, Canada, 1988-2012. We
calculated the prevalence of congenital heart defects at birth according to the
number of days women were exposed to maximum temperature >= 30 degrees C. In log
binomial regression models, we estimated prevalence ratios (PR) and 95%
confidence intervals (CI) for the relationship of temperature with seven critical
and eight noncritical heart defects, adjusted for pregnancy characteristics.
RESULTS: Prevalence of congenital heart defects was 979.5 per 100,000 for 10 days
or more of temperature >= 30 degrees C compared with 878.9 per 100,000 for 0 days
of exposure. Temperature was more precisely associated with noncritical than
critical defects, which had lower prevalence. Fetuses exposed to 15 days of
temperature >= 30 degrees C between 2 and 8 weeks postconception had 1.06 times
the risk of critical defects (95% CI: 0.67, 1.67) and 1.12 times the risk of
noncritical defects (95% CI: 0.98, 1.29) relative to 0 days. Associations were
higher for atrial septal defects (PR 1.37, 95% CI: 1.10, 1.70) than for other
noncritical defects. For atrial septal defects, associations with elevated
temperatures began the 3rd week postconception. CONCLUSIONS: Extreme heat
exposure during the first trimester may be associated with noncritical heart
defects, especially of the atrial septum. Citation: Auger N, Fraser WD, Sauve R,
Bilodeau-Bertrand M, Kosatsky T. 2017. Risk of congenital heart defects after
ambient heat exposure early in pregnancy. Environ Health Perspect 125:8-14;
http://dx.doi.org/10.1289/EHP171.
PMID- 27494595
TI - Effect of hand cooling on body temperature, cardiovascular and perceptual
responses during recumbent cycling in a hot environment.
AB - The purpose of this study was to quantify physiological and perceptual responses
to hand immersion in water during recumbent cycling in a hot environment. Seven
physically active males (body mass 79.8 +/- 6.3 kg; stature 182 +/- 5 cm; age 23
+/- 3 years) immersed their hands in 8, 14 and 34 degrees C water whilst cycling
at an intensity (W) equivalent to 50% [Formula: see text]O2peak for 60 min in an
environmental chamber (35 degrees C, 50% relative humidity). 8 and 14 degrees C
water attenuated an increase in body temperature, and lowered cardiorespiratory
and skin blood flow demands. These effects were considered to be practically
beneficial (standardised effect size > 0.20). There was a tendency for 8 and 14
degrees C to extend exercise duration versus 34 degrees C (>7%). Heart rate,
intestinal, mean skin and mean body temperature were less in 8 degrees C compared
to 14 degrees C; these differences were considered practically beneficial.
Augmented heat loss at the palm-water surface might enable cooler blood to return
to the body and limit physiological strain. These findings provide a mechanistic
basis for continuous hand cooling and indicate that endurance exercise in hot
environments could be improved using this method. Future research should
investigate its effectiveness during cycling and running performance.
PMID- 27494596
TI - Relationship between antibiotic residues and occurrence of resistant bacteria in
Nile tilapia (Oreochromisniloticus) cultured in cage-farm.
AB - The aim of this study was to investigate the relationship between antibiotic
residues found in the muscle of cage-farm-raised Nile tilapia
(Oreochromisniloticus), the occurrence of resistant bacteria, and the sanitary
practices adopted by farmers in Ilha Solteira reservoir, Brazil. Nine fish (three
small fish, 40-200 g; three medium-sized fish, 200-500 g; and three large fish,
500-800 g) were collected from four cage farms every three months from April 2013
to January 2014. Ten antibiotic residues were determined using liquid
chromatography-mass spectrometry, and bacteria were isolated and tested for
antibiotic resistance to determine the multiple antibiotic resistance (MAR)
index. Only three antibiotics (oxytetracycline, tetracycline, and florfenicol)
were detected in the muscle of Nile tilapia, and their residues were the highest
in small fish; however, the MAR index was higher in large fish. In addition, a
direct positive relationship between the MAR index and the concentration of
antibiotic residues in Nile tilapia was found. Overall, the adoption of
prophylactic management practices improved the sanitary status of cage farms,
reducing bacterial infections and hampering the development of antibiotic
resistant bacteria.
PMID- 27494597
TI - Development of an Age Band on the ManuVis for 3-Year-Old Children with Visual
Impairments.
AB - AIM: To compare fine motor performance of 3-year-old children with visual
impairment with peers having normal vision, to provide reference scores for 3
year-old children with visual impairment on the ManuVis, and to assess inter
rater reliability. METHOD: 26 children with visual impairment (mean age: 3 years
7 months (SD 3 months); 17 boys) and 28 children with normal vision (mean age: 3
years 7 months (SD 4 months); 14 boys) participated in the study. The ManuVis age
band for 3-year-old children comprised two one-handed tasks, two two-handed
tasks, and a pre-writing task. RESULTS: Children with visual impairment needed
more time on all tasks (p < .01) and performed the pre-writing task less
accurately than children with normal vision (p < .001). Children aged 42-47
months performed significantly faster on two tasks and had better total scores
than children aged 36-41 months (p < .05). Inter-rater reliability was excellent
(Intra-class Correlation Coefficient = 0.96-0.99). CONCLUSIONS: The ManuVis age
band for 3-year-old children is appropriate to assess fine motor skills, and is
sensitive to differences between children with visual impairment and normal
vision and between half-year age groups. Reference scores are provided for 3-year
old children with visual impairment to identify delayed fine motor development.
PMID- 27494598
TI - Aurora kinase and RUNX: Reaching beyond transcription.
PMID- 27494599
TI - Derivation of a time dependent Schrodinger equation as the quantum mechanical
Landau-Lifshitz-Bloch equation.
AB - The derivation of the time dependent Schrodinger equation with transversal and
longitudinal relaxation, as the quantum mechanical analog of the classical Landau
Lifshitz-Bloch equation, has been described. Starting from the classical Landau
Lifshitz-Bloch equation the transition to quantum mechanics has been performed
and the corresponding von-Neumann equation deduced. In a second step the time
Schrodinger equation has been derived. Analytical proofs and computer simulations
show the correctness and applicability of the derived Schrodinger equation.
PMID- 27494600
TI - Ecological Contexts of Index Cases and Spillover Events of Different
Ebolaviruses.
AB - Ebola virus disease afflicts both human and animal populations and is caused by
four ebolaviruses. These different ebolaviruses may have distinct reservoir hosts
and ecological contexts that determine how, where, and when different ebolavirus
spillover events occur. Understanding these virus-specific relationships is
important for preventing transmission of ebolaviruses from wildlife to humans. We
examine the ecological contexts surrounding 34 human index case infections of
ebolaviruses from 1976-2014. Determining possible sources of spillover from
wildlife, characterizing the environment of each event, and creating ecological
niche models to estimate habitats suitable for spillover, we find that index case
infections of two ebolaviruses, Ebola virus and Sudan virus, have occurred under
different ecological contexts. The index cases of Ebola virus infection are more
associated with tropical evergreen broadleaf forests and consuming bushmeat than
the cases of Sudan virus. Given these differences, we emphasize caution when
generalizing across different ebolaviruses and that location and virus-specific
ecological knowledge will be essential to unravelling how human and animal
behavior lead to the emergence of Ebola virus disease.
PMID- 27494602
TI - Three-Dimensionally Homoconjugated Carbon-Bridged Oligophenylenevinylene for
Perovskite Solar Cells.
AB - Stabilization of the radical cationic state of a donor molecule by 3-D
homoconjugation was probed using a substituted carbon-bridged
oligophenylenevinylene backbone (COPV, or 5,5-diarylindeno[2,1-a]indenes). For
molecules bearing electron-donating groups as the 5,5-aryl moieties, a one
electron oxidation of the COPV backbone results in delocalization of the cationic
charge over the whole molecule with a small reorganization energy. The compounds
forming a stable radical cation by 3-D homoconjugation produce a uniform
amorphous film and show high short-circuit current, high fill factor, and hence
high power-conversion efficiency when used as a hole-transporting layer of an
organic-inorganic hybrid lead perovskite solar cell. This material thus shows a
performance and stability in air comparable to those obtained with the benchmark
material, spiro-MeOTAD.
PMID- 27494601
TI - The Temporal Signature of Memories: Identification of a General Mechanism for
Dynamic Memory Replay in Humans.
AB - Reinstatement of dynamic memories requires the replay of neural patterns that
unfold over time in a similar manner as during perception. However, little is
known about the mechanisms that guide such a temporally structured replay in
humans, because previous studies used either unsuitable methods or paradigms to
address this question. Here, we overcome these limitations by developing a new
analysis method to detect the replay of temporal patterns in a paradigm that
requires participants to mentally replay short sound or video clips. We show that
memory reinstatement is accompanied by a decrease of low-frequency (8 Hz) power,
which carries a temporal phase signature of the replayed stimulus. These replay
effects were evident in the visual as well as in the auditory domain and were
localized to sensory-specific regions. These results suggest low-frequency phase
to be a domain-general mechanism that orchestrates dynamic memory replay in
humans.
PMID- 27494604
TI - Removal of sulfamethazine antibiotics using CeFe-graphene nanocomposite as
catalyst by Fenton-like process.
AB - The presence of sulfonamide (SMT) antibiotics in aquatic environments has
received increasing attention in recent years, and they are ubiquitous pollutants
which cannot be effectively removed by conventional wastewater treatment
processes. In this paper, the nanocomposites Ce(0)/Fe(0)-reduced graphene oxide
(Ce(0)/Fe(0)-RGO) were synthesized through chemical reduction method, and
characterized by Raman and FTIR before and after use. The addition of RGO can
prevent the agglomeration of Ce(0) and Fe(0). The elimination of SMT can be
divided into adsorption and degradation process. The adsorption of SMT onto the
catalyst can enhance its degradation. The effect of pH value, concentration of
H2O2, catalyst dosage, temperature and initial SMT concentration on the removal
efficiency of SMT was determined. When pH = 7, T = 25 degrees C, H2O2 = 8 mM,
Ce(0)/Fe(0)-RGO = 0.5 g/L, SMT = 20 mg/L, the removal efficiency of SMT and TOC
was 99% and 73%, respectively. The stability of the catalysts was evaluated with
repeated batch experiments using ethanol, water and acid as solvents to wash the
used catalysts, respectively. The surface change of the catalysts after each use
was characterized by Raman and FTIR analysis. The intermediates were detected by
GC-MS and IC, the possible degradation pathway of SMT was tentatively proposed.
PMID- 27494605
TI - Alkali modified hydrochar of grape pomace as a perspective adsorbent of Pb(2+)
from aqueous solution.
AB - Hydrochar produced via hydrothermal carbonization of grape pomace was considered
as novel sorbent of Pb(2+) from aqueous solution. In order to enhance the
adsorption capacity, hydrochar was chemically modified using 2 M KOH solution.
Both materials were characterized by Fourier transform infrared spectroscopy,
scanning electron microscopy and X-ray diffraction technique. Batch experiments
were performed to examine the effect of sorbent dosage, pH and contact time.
Obtained results showed that the KOH treatment increased the sorption capacity of
hydrochar from 27.8 mg g(-1) up to 137 mg g(-1) at pH 5. Adsorption of lead on
either of the materials was achieved through ion-exchange mechanism,
chemisorption and Pb(2+)-pi interaction. The Sips isotherm model gave the best
fit with the experimental data obtained for Pb(2+) sorption using activated
hydrochar. The adsorption kinetic followed a pseudo second-order model.
Thermodynamic parameters implied that the Pb(2+) binding for hydrochar surface
was spontaneous and exothermic process. Findings from this work suggest that the
hydrothermal carbonization is a promising route for production of efficient Pb
(2+) sorbents for wastewater treatment.
PMID- 27494603
TI - Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.
AB - Microphthalmia is characterized by abnormally small eyes and usually retinal
dysplasia, accounting for up to 11% of the blindness in children. Right now there
is no effective treatment for the disease, and the underlying mechanisms,
especially how retinal dysplasia develops from microphthalmia and whether it
depends on the signals from lens ectoderm are still unclear. Mutations in genes
of the TGF-beta superfamily have been noted in patients with microphthalmia.
Using conditional knockout mice, here we address the question that whether ocular
surface ectoderm-derived Smad4 modulates retinal development. We found that loss
of Smad4 specifically on surface lens ectoderm leads to microphthalmia and
dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the
delayed or failed differentiation and apoptosis of retinal cells. Microarray
analyses revealed that members of Hedgehog and Wnt signaling pathways are
affected in the knockout retinas, suggesting that ocular surface ectoderm-derived
Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest
that defective of ocular surface ectoderm may affect retinal development.
PMID- 27494606
TI - Influence of exchange group of modified glycidyl methacrylate polymer on phenol
removal: A study by batch and continuous flow processes.
AB - Contamination of water by phenol is potentially a serious problem due to its high
toxicity and its acid character. In this way some treatment process to remove or
reduce the phenol concentration before contaminated water disposal on the
environment is required. Currently, phenol can be removed by charcoal adsorption,
but this process does not allow easy regeneration of the adsorbent. In contrast,
polymeric resins are easily regenerated and can be reused in others cycles of
adsorption process. In this work, the interaction of phenol with two polymeric
resins was investigated, one of them containing a weakly basic anionic exchange
group (GD-DEA) and the other, a strongly basic group (GD-QUAT). Both ion exchange
resins were obtained through chemical modifications from a base porous resin
composed of glycidyl methacrylate (GMA) and divinyl benzene (DVB). Evaluation
tests with resins were carried out with 30 mg/L of phenol in water solution, at
pH 6 and 10, employing two distinct processes: (i) batch, to evaluate the effect
of temperature, and (ii) continuous flow, to assess the breakthrough of the
resins. Batch tests revealed that the systems did not follow the model proposed
by Langmuir due to the negative values obtained for the constant b and for the
maximum adsorption capacity, Q0. However, satisfactory results for the constants
KF and n allowed assuming that the behavior of systems followed the Freundlich
model, leading to the conclusion that resin GD-DEA had the best interaction with
the phenol when in a solution having pH 10 (phenoxide ions). The continuous flow
tests corroborated this conclusion since the performance of GD-DEA in removing
phenol was also best at pH 10, indicating that the greater availability of the
electron pair in the resin with the weakly basic donor group contributed to
enhance the resin's interaction with the phenoxide ions.
PMID- 27494607
TI - Groundwater level prediction using a SOM-aided stepwise cluster inference model.
AB - Accurate groundwater level (GWL) prediction can contribute to sustaining reliable
water supply to domestic, agricultural and industrial uses as well as ecological
services, especially in arid and semi-arid areas. In this paper, a regional GWL
modeling framework was first presented through coupling both spatial and temporal
clustering techniques. Specifically, the self-organizing map (SOM) was applied to
identify spatially homogeneous clusters of GWL piezometers, while GWL time series
forecasting was performed through developing a stepwise cluster multisite
inference model with various predictors including climate conditions, well
extractions, surface runoffs, reservoir operations and GWL measurements at
previous steps. The proposed modeling approach was then demonstrated by a case of
an arid irrigation district in the western Hexi Corridor, northwest China.
Spatial clustering analysis identified 6 regionally representative central
piezometers out of 30, for which sensitivity and uncertainty analysis were
carried out regarding GWL predictions. As the stepwise cluster tree provided
uncertain predictions, we added an AR(1) error model to the mean prediction to
forecast GWL 1 month ahead. Model performance indicators suggest that the
modeling system is a useful tool to aid decision-making for informed groundwater
resource management in arid areas, and would have a great potential to extend its
applications to more areas or regions in the future.
PMID- 27494608
TI - High prevalence of anti-hepatitis E virus antibodies among blood donors in
central Italy, February to March 2014.
AB - Prevalence of anti-hepatitis E virus (HEV) antibodies is highly variable in
developed countries, which seems partly due to differences in assay sensitivity.
Using validated sensitive assays, we tested 313 blood donors attending a hospital
transfusion unit in central Italy in January and February 2014 for anti-HEV IgG
and IgM and HEV RNA. Data on HEV exposure were collected from all donors. Overall
anti-HEV IgG prevalence was 49% (153/313). Eating raw dried pig-liver sausage was
the only independent predictor of HEV infection (adjusted prevalence rate ratio =
2.14; 95% confidence interval: 1.23-3.74). Three donors were positive for either
anti-HEV IgM (n = 2; 0.6%) or HEV RNA (n = 2; 0.6%); they were completely
asymptomatic, without alanine aminotransferase (ALT) abnormalities. Of the two
HEV RNA-positive donors (both harbouring genotype 3), one was anti-HEV IgG- and
IgM-positive, the other was anti-HEV IgG- and IgM-negative. The third donor was
positive for anti-HEV IgG and IgM but HEV RNA-negative. HEV infection is
therefore hyperendemic among blood donors (80% men 18-64 years-old) from central
Italy and associated with local dietary habits. Nearly 1% of donors have acute or
recent infection, implying potential transmission to blood recipients. Neither
ALT nor anti-HEV IgM testing seems useful to prevent transfusion-transmitted HEV
infection.
PMID- 27494609
TI - Early- or mid-trimester amniocentesis biomarkers for predicting preterm delivery:
a meta-analysis.
AB - OBJECTIVE: To determine the value of early- or mid-trimester amniotic fluid
levels of interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8), and glucose
for predicting preterm delivery. METHODS: Randomized controlled trials and two
arm prospective, retrospective, cohorts, and case-controlled studies in which
patients received early- or mid-trimester amniocentesis for karyotyping, and
biomarker testing of the amniotic fluid was performed and delivery data were
available were included in the analysis. RESULTS: Outcome measures were the
associations of amniotic fluid IL-6, MMP-8, and glucose levels with preterm
delivery. Differences in means with 95% confidence intervals (CIs) were
calculated. Of 288 articles identified, 14 were included in the meta-analysis
with a total of 675 patients who had preterm birth and 2518 patients who had term
births. The preterm-delivery group had significantly higher amniotic fluid IL-6
and MMP-8 levels, and a significantly lower glucose level than the term delivery
group (IL-6: difference in means = 0.32, 95% CI: 0.22-0.43, p < 0.001; MMP-8:
difference in means = 4.47, 95% CI: 0.83-8.11), p = 0.016; glucose: difference in
means = -5.22, 95% CI: -8.19 to -2.26, p = 0.001) Conclusion: Early- or mid
trimester amniotic fluid IL-6, MMP-8, and glucose levels are useful for
predicting the risk of preterm delivery. KEY MESSAGES Median amniotic fluid
ferritin and IL-6 levels, and mean amniotic fluid ALP levels were higher in the
preterm group. The preterm-delivery group had significantly higher amniotic fluid
IL-6 and MMP-8 levels, and a significantly lower glucose level than the term
delivery group.
PMID- 27494610
TI - Magnetic Particle Imaging for High Temporal Resolution Assessment of Aneurysm
Hemodynamics.
AB - PURPOSE: The purpose of this work was to demonstrate the capability of magnetic
particle imaging (MPI) to assess the hemodynamics in a realistic 3D aneurysm
model obtained by additive manufacturing. MPI was compared with magnetic
resonance imaging (MRI) and dynamic digital subtraction angiography (DSA).
MATERIALS AND METHODS: The aneurysm model was of saccular morphology (7 mm dome
height, 5 mm cross-section, 3-4 mm neck, 3.5 mm parent artery diameter) and
connected to a peristaltic pump delivering a physiological flow (250 mL/min) and
pulsation rate (70/min). High-resolution (4 h long) 4D phase contrast flow
quantification (4D pc-fq) MRI was used to directly assess the hemodynamics of the
model. Dynamic MPI, MRI, and DSA were performed with contrast agent injections (3
mL volume in 3 s) through a proximally placed catheter. RESULTS AND DISCUSSION:
4D pc-fq measurements showed distinct pulsatile flow velocities (20-80 cm/s) as
well as lower flow velocities and a vortex inside the aneurysm. All three dynamic
methods (MPI, MRI, and DSA) also showed a clear pulsation pattern as well as
delayed contrast agent dynamics within the aneurysm, which is most likely caused
by the vortex within the aneurysm. Due to the high temporal resolution of MPI and
DSA, it was possible to track the contrast agent bolus through the model and to
estimate the average flow velocity (about 60 cm/s), which is in accordance with
the 4D pc-fq measurements. CONCLUSIONS: The ionizing radiation free, 4D high
resolution MPI method is a very promising tool for imaging and characterization
of hemodynamics in human. It carries the possibility of overcoming certain
disadvantages of other modalities like considerably lower temporal resolution of
dynamic MRI and limited 2D characteristics of DSA. Furthermore, additive
manufacturing is the key for translating powerful pre-clinical techniques into
the clinic.
PMID- 27494612
TI - Relationship between Mid-Upper Arm Circumference and Body Mass Index in
Inpatients.
AB - INTRODUCTION: Nutritional screening is a fundamental aspect of the initial
evaluation of the hospitalised patient. Body Mass Index (BMI) in association with
other parameters is a good marker of malnutrition (<18.5 kg/m2), but it presents
the handicap that the great majority of patients cannot be weighed and measured.
For this reason it is necessary to find other indicators that can be measured in
these patients. OBJECTIVES: 1) Analyse the relationship between BMI and Mid-Upper
Arm Circumference (MUAC); 2) establish a cut-off point of MUAC equivalent to BMI
<18.5 kg/m2. MATERIALS AND METHODS: The anthropometric data of patients
hospitalised over the period 2004-2013 were retrospectively revised. The
following variables were collected: weight, height, BMI, MUAC, sex and age.
RESULTS: 1373 patients were evaluated, who presented a mean weight of: 65.04+/
15.51 kg; height: 1.66+/-0.09 m; BMI: 23.48+/-5.03 kg/m2; MUAC: 26.95+/-4.50 cm;
age: 56.24+/-16.77. MUAC correlates suitably to BMI by means of the following
equation (simple linear regression): BMI = - 0.042 + 0.873 x MUAC (cm) (R2 =
0.609), with a Pearson r value of 0.78 (p<0.001). The area under the curve of
MUAC for the diagnosis of malnutrition was 0.92 (95% CI: 0.90-0.94; p<0.001). The
MUAC value <=22.5 cm presented a sensitivity of 67.7%, specificity of 94.5%, and
a correct classification of 90%. No significant statistical differences were
found in the cut-off point of MUAC for the diagnosis of malnutrition based on sex
(p = 0.115) and age (p = 0.694). CONCLUSIONS: 1) MUAC correlates positively and
significantly with BMI. 2) MUAC <= 22.5 cm correlates properly with a BMI of
<18.5 kg/m2, independent of the age or sex of the patient, although there are
other alternatives. MUAC constitutes a useful tool as a marker of malnutrition,
fundamentally in patients for whom weight and height cannot be determined.
PMID- 27494611
TI - Comprehensive Analysis of the Transcriptional and Mutational Landscape of
Follicular and Papillary Thyroid Cancers.
AB - Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are
indistinguishable by preoperative diagnosis due to their similar histological
features. Here we report the first RNA sequencing study of these tumors, with
data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77
classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs
(FVPTCs) to observe the differences in their molecular properties. Mutations in
H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or
FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8
PPARG), but a high frequency of that in PTC (17.60%). The frequencies of
BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC,
and those of FVPTC were intermediate between miFTC and cPTC. Gene expression
analysis demonstrated three molecular subtypes regardless of their histological
features, including Non-BRAF-Non-RAS (NBNR), as well as BRAF-like and RAS-like.
The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1,
PTEN, SOS1, SPOP, and PAX8-PPARG. The transcriptome of miFTC or encapsulated
FVPTC was indistinguishable from that of FA, providing a molecular explanation
for the similarly indolent behavior of these tumors. We identified upregulation
of genes that are related to mitochondrial biogenesis including ESRRA and
PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number
variations were correlated to histological and molecular characteristics. These
results expanded the current molecular understanding of thyroid cancer and may
lead to new diagnostic and therapeutic approaches to the disease.
PMID- 27494613
TI - Azine-Hydrazone Tautomerism of Guanylhydrazones: Evidence for the Preference
Toward the Azine Tautomer.
AB - Guanylhydrazones have been known for a long time and have wide applications in
organic synthesis, medicinal chemistry, and material science; however, little
attention has been paid toward their electronic and structural properties.
Quantum chemical analysis on several therapeutically important guanylhydrazones
indicated that all of them prefer the azine tautomeric state (by about 3-12
kcal/mol). A set of simple and conjugated azines were designed using quantum
chemical methods, whose tautomeric preference toward the azine tautomer is in the
range of 3-8 kcal/mol. Twenty new azines were synthesized and isolated in their
neutral state. Variable temperature NMR study suggests existence of the azine
tautomer even at higher temperatures with no traces of the hydrazone tautomer.
The crystal structures of two representative compounds confirmed that the title
compounds prefer to exist in their azine tautomeric form.
PMID- 27494615
TI - Sequencing and Characterization of the Invasive Sycamore Lace Bug Corythucha
ciliata (Hemiptera: Tingidae) Transcriptome.
AB - The sycamore lace bug, Corythucha ciliata (Hemiptera: Tingidae), is an invasive
forestry pest rapidly expanding in many countries. This pest poses a considerable
threat to the urban forestry ecosystem, especially to Platanus spp. However, its
molecular biology and biochemistry are poorly understood. This study reports the
first C. ciliata transcriptome, encompassing three different life stages (Nymphs,
adults female (AF) and adults male (AM)). In total, 26.53 GB of clean data and
60,879 unigenes were obtained from three RNA-seq libraries. These unigenes were
annotated and classified by Nr (NCBI non-redundant protein sequences), Nt (NCBI
non-redundant nucleotide sequences), Pfam (Protein family), KOG/COG (Clusters of
Orthologous Groups of proteins), Swiss-Prot (A manually annotated and reviewed
protein sequence database), and KO (KEGG Ortholog database). After all pairwise
comparisons between these three different samples, a large number of
differentially expressed genes were revealed. The dramatic differences in global
gene expression profiles were found between distinct life stages (nymphs and AF,
nymphs and AM) and sex difference (AF and AM), with some of the significantly
differentially expressed genes (DEGs) being related to metamorphosis, digestion,
immune and sex difference. The different express of unigenes were validated
through quantitative Real-Time PCR (qRT-PCR) for 16 randomly selected unigenes.
In addition, 17,462 potential simple sequence repeat molecular markers were
identified in these transcriptome resources. These comprehensive C. ciliata
transcriptomic information can be utilized to promote the development of
environmentally friendly methodologies to disrupt the processes of metamorphosis,
digestion, immune and sex differences.
PMID- 27494614
TI - Predictive Big Data Analytics: A Study of Parkinson's Disease Using Large,
Complex, Heterogeneous, Incongruent, Multi-Source and Incomplete Observations.
AB - BACKGROUND: A unique archive of Big Data on Parkinson's Disease is collected,
managed and disseminated by the Parkinson's Progression Markers Initiative
(PPMI). The integration of such complex and heterogeneous Big Data from multiple
sources offers unparalleled opportunities to study the early stages of prevalent
neurodegenerative processes, track their progression and quickly identify the
efficacies of alternative treatments. Many previous human and animal studies have
examined the relationship of Parkinson's disease (PD) risk to trauma, genetics,
environment, co-morbidities, or life style. The defining characteristics of Big
Data-large size, incongruency, incompleteness, complexity, multiplicity of
scales, and heterogeneity of information-generating sources-all pose challenges
to the classical techniques for data management, processing, visualization and
interpretation. We propose, implement, test and validate complementary model
based and model-free approaches for PD classification and prediction. To explore
PD risk using Big Data methodology, we jointly processed complex PPMI imaging,
genetics, clinical and demographic data. METHODS AND FINDINGS: Collective
representation of the multi-source data facilitates the aggregation and
harmonization of complex data elements. This enables joint modeling of the
complete data, leading to the development of Big Data analytics, predictive
synthesis, and statistical validation. Using heterogeneous PPMI data, we
developed a comprehensive protocol for end-to-end data characterization,
manipulation, processing, cleaning, analysis and validation. Specifically, we (i)
introduce methods for rebalancing imbalanced cohorts, (ii) utilize a wide
spectrum of classification methods to generate consistent and powerful phenotypic
predictions, and (iii) generate reproducible machine-learning based
classification that enables the reporting of model parameters and diagnostic
forecasting based on new data. We evaluated several complementary model-based
predictive approaches, which failed to generate accurate and reliable diagnostic
predictions. However, the results of several machine-learning based
classification methods indicated significant power to predict Parkinson's disease
in the PPMI subjects (consistent accuracy, sensitivity, and specificity exceeding
96%, confirmed using statistical n-fold cross-validation). Clinical (e.g.,
Unified Parkinson's Disease Rating Scale (UPDRS) scores), demographic (e.g.,
age), genetics (e.g., rs34637584, chr12), and derived neuroimaging biomarker
(e.g., cerebellum shape index) data all contributed to the predictive analytics
and diagnostic forecasting. CONCLUSIONS: Model-free Big Data machine learning
based classification methods (e.g., adaptive boosting, support vector machines)
can outperform model-based techniques in terms of predictive precision and
reliability (e.g., forecasting patient diagnosis). We observed that statistical
rebalancing of cohort sizes yields better discrimination of group differences,
specifically for predictive analytics based on heterogeneous and incomplete PPMI
data. UPDRS scores play a critical role in predicting diagnosis, which is
expected based on the clinical definition of Parkinson's disease. Even without
longitudinal UPDRS data, however, the accuracy of model-free machine learning
based classification is over 80%. The methods, software and protocols developed
here are openly shared and can be employed to study other neurodegenerative
disorders (e.g., Alzheimer's, Huntington's, amyotrophic lateral sclerosis), as
well as for other predictive Big Data analytics applications.
PMID- 27494616
TI - The Emergence of Quinolone Resistant Shigella sonnei, Pondicherry, India.
AB - Ciprofloxacin resistant Shigella sonnei across the globe have been increasing
alarmingly. In order to understand the emergence of S.sonnei with respect to
ciprofloxacin resistance in our patient population, the following study was
carried out. Of the 184 Shigella sp. Isolated from 2012 to 2015, 34 S.sonnei
which were confirmed by standard methods and subjected to antimicrobial
susceptibility testing were selected. The minimum inhibitory concentrations
(MICs) of 16/34 quinolone resistant isolates tested ranged from 4micrograms/ml to
16micrograms/ml for ciprofloxacin, from 16 micrograms/ml to 64 micrograms/ml for
ofloxacin and from 16micrograms/ml to 64micrograms/ml for levofloxacin. Sequence
determination of the quinolone resistance determining regions of gyrA, gyrB,
parC, and parE genes showed mutations in GyrA at Gln69/Trp, Phe71/Ser, Ser72/Pro,
Met75/Leu, Ser90/Cys, Met94/Leu, His106/Pro, Asn161/His, Thr163/Ala and in ParC
at Ala64/Asp. Among the plasmid-mediated quinolone resistance (PMQRs) targets
investigated,qnrB was the most (93.7%) prevalent followed by qnrC (18.7%). None
hadqnrA, qnrS and qepA. Two (0.1%) of the isolates harboured theaac(6')-lb gene.
Drug accumulation assay detected the presence of efflux pump activity in 9/15
(60%) among ciprofloxacin resistant isolates. All isolates harboured the ipaH
gene followed by ial (17.6%), sen (11.7%), set1A&set1B (5.8%) genes. None had
stx1 element. PCR for Enterobacterial repetitive intergenic consensus (ERIC)
sequences resulted in 4 unique clusters, of which Type III was the most (44%)
dominant but there was no correlation between the ERIC types and the antibiotic
resistance pattern or the virulence profile. A documented increase in S.sonnei
harbouring the qnrgenes and some unusual genes like set1Aand indicate an ongoing
process of horizontal gene transfer. The accumulation of novel mutations in GyrA
and ParC in the presence of efflux pump and PMQR genes contributed to the raised
MIC to quinolones. These findings are crucial in our understanding of quinolone
resistance in these isolates.
PMID- 27494617
TI - Cut-Off Value for Pain Sensitivity Questionnaire in Predicting Surgical Success
in Patients with Lumbar Disc Herniation.
AB - Various factors related to predict surgical success were studied; however, a
standard cut-off point for the Pain Sensitivity Questionnaire (PSQ) measure has
not yet been established for a favorable surgical outcome for lumbar disc
herniation (LDH). This study was to find the optimal cut-off point on the PSQ to
distinguish surgical success in patients with LDH. A total of 154 patients with
LDH consecutively referred to our clinic were enrolled into this prospective
study between February 2011 and January 2014. All participants completed the PSQ.
Patients completed the Oswestry Disability Index (ODI) score before surgery, and
at 2 years after surgery. Surgical success was defined as a 13-point improvement
from the baseline ODI scores. The cut-off value for PSQ was determined by the
receiver-operating characteristic curve (ROC). The mean age of patients was
49.3+/-9.6 years, and there were 80 women. The mean time for follow-up assessment
was 31+/-5 months (range 24-35). Post-surgical success was 79.9% (n = 123) at 2
years follow up. The mean score for the total PSQ, PSQ-minor, and PSQ-moderate
were 6.0 (SD = 1.6), 5.4 (SD = 1.9) and 6.5 (SD = 1.7), respectively. Total PSQ
score was also significantly correlated with the total scores of the ODI. The
optimal total PSQ cut-off point was determined as > 5.2 to predict surgical
success in LDH patients, with 80.0% sensitivity and 75.6% specificity (AUC-0.814,
95% CI 0.703-0.926). This study showed that the PSQ could be considered a
parameter for predicting surgical success in patients with LDH, and can be useful
in clinical practice.
PMID- 27494618
TI - Effects of levetiracetam monotherapy on sperm parameters and sex hormones: Data
from newly diagnosed patients with epilepsy.
AB - PURPOSE: Epilepsy has an impact on the reproductive system. Males with epilepsy
have lower fertility rates, hypo-sexuality and reduced potency compared with the
general population. Anti-epileptic drugs and epilepsy itself are thought to be
responsible for this reduced fertility. LEV is a second-generation anti-epileptic
agent with low incidences of both adverse effects and drug-drug interactions. In
this study, we have investigated the effects of LEV treatment on sex hormones and
sperm parameters in newly diagnosed epilepsy patients. METHODS: We recruited 26
males with newly diagnosed epilepsy and introduced LEV monotherapy. Patients were
divided into two groups depending on whether they had partial or generalized
seizures. We acquired the results of pre- and post-treatment sperm analyses and
serum sex hormone levels. We also recorded the maximum dose, daily dose and
treatment duration for each individual. Pre- and post-treatment comparisons and
correlations between both sperm and sex hormone parameters and both treatment
duration and dose were determined. RESULTS: Pre- and post-treatment sex hormone
levels were not significantly different. The total sperm count, percentage of
normal morphology and functional sperm count tested after treatment were
significantly lower in both groups compared with pre-treatment values (p<0.05).
There was a moderate correlation between daily dose and reduction in functional
sperm count (r: 0.41, p: 0.034). CONCLUSIONS: Our findings confirm that LEV
treatment of newly diagnosed epilepsy patients decreases sperm parameters without
altering sex hormone levels. Our results may guide the choice of anti-epileptic
drug treatment among men with epilepsy.
PMID- 27494619
TI - Tools and strategies for scarless allele replacement in Drosophila using
CRISPR/Cas9.
AB - Genome editing via the CRISPR/Cas9 RNA-guided nuclease system has opened up
exciting possibilities for genetic analysis. However, technical challenges
associated with homology-directed repair have proven to be roadblocks for
producing changes in the absence of unwanted, secondary mutations commonly known
as "scars." To address these issues, we developed a 2-stage, marker-assisted
strategy to facilitate precise, "scarless" edits in Drosophila with a minimal
requirement for molecular screening. Using this method, we modified 2 base pairs
in a gene of interest without altering the final sequence of the CRISPR cut
sites. We executed this 2-stage allele swap using a novel transformation marker
that drives expression in the pupal wings, which can be screened for in the
presence of common eye-expressing reporters. The tools we developed can be used
to make a single change or a series of allelic substitutions in a region of
interest in any D. melanogaster genetic background as well as in other Drosophila
species.
PMID- 27494620
TI - Microscopic Analyses of Latent and Visible Monilinia fructicola Infections in
Nectarines.
AB - Little is known about the histologic features of a latent Monilinia fructicola
infection and brown rot in infected fruit. This report informs on the results of
an investigation whose aim was to analyze the microanatomy of nectarines with a
latent and visible M. fructicola infection. Mature nectarines were inoculated
with an M. fructicola isolate and incubated at 25 degrees C for 0, 24, 48, 72, or
96 hours in the dark. For investigating the latent infection process, the
inoculated nectarines were first incubated at 25 degrees C for 24 hours in the
dark and then incubated at 4 degrees C for 72, 144, 216, and 288 hours in the
dark. At the end of the incubation, samples of nectarine tissue were excised from
the inoculation points and prepared for light and transmission electron
microscopic examinations. No signs of disease were seen on the surface of
nectarines with a latent infection over the 288-hour incubation period. When the
tissue samples were microscopically examined, M. fructicola colonized the stomata
and this stomatal colonization progressively increased over time and was
associated with gradual collapse of the epidermal cells and colonization of the
subepidermis. In nectarines with visible brown rot, the disease usually appeared
after 24 hours on the surface and in the uppermost layers of epidermal cells,
which began to collapse after 48 hours. Subsequently, the diseased tissues of the
nectarines displayed (a) colonization of the epidermis and mesocarp by M.
fructicola with thin and thick hyphae, (b) collapse and disruption of epidermal
and mesocarpic cells, (c) lysogenic cavities in the subepidermis and mesocarp,
(d) degradation of the cuticle and epidermis, and (e) M. fructicola sporulation.
M. fructicola is active during latent infections because slow and progressive
colonization of nectarine subcuticular cells by the fungus occurs.
PMID- 27494622
TI - First thoughts on the effects on the protection of laboratory animals of the UK's
departure from the European Union.
PMID- 27494621
TI - Intragenic ERG Deletions Do Not Explain the Biology of ERG-Related Acute
Lymphoblastic Leukemia.
AB - Intragenic ERG deletions occur in 3-5% of B-cell precursor acute lymphoblastic
leukemia, specifically in B-other subtype lacking the classifying genetic
lesions. They represent the only genetic lesion described so far present in the
majority of cases clustering into a subgroup of B-other subtype characterized by
a unique gene expression profile, probably sharing a common, however, not yet
fully described, biological background. We aimed to elucidate whether ERG
deletions could drive the specific biology of this ERG-related leukemia subgroup
through expression of aberrant or decreased expression of wild type ERG isoforms.
We showed that leukemic cells with endogenous ERG deletion express an aberrant
transcript translated into two proteins in transfected cell lines and that one of
these proteins colocalizes with wild type ERG. However, we did not confirm
expression of the proteins in acute lymphoblastic leukemia cases with endogenous
ERG deletion. ERG deletions resulted in significantly lower expression of wild
type ERG transcripts compared to B-other cases without ERG deletion. However,
cases with subclonal ERG deletion, clustering to the same ERG deletion associated
subgroup, presented similar levels of wild type ERG as cases without ERG
deletion. In conclusion, our data suggest that neither the expression of aberrant
proteins from internally deleted allele nor the reduced expression of wild type
ERG seem to provide a plausible explanation of the specific biology of ERG
related leukemia subgroup.
PMID- 27494623
TI - The use of in vivo, ex vivo, in vitro, computational models and volunteer studies
in vision research and therapy, and their contribution to the Three Rs.
AB - Much is known about mammalian vision, and considerable progress has been achieved
in treating many vision disorders, especially those due to changes in the eye, by
using various therapeutic methods, including stem cell and gene therapy. While
cells and tissues from the main parts of the eye and the visual cortex (VC) can
be maintained in culture, and many computer models exist, the current non-animal
approaches are severely limiting in the study of visual perception and
retinotopic imaging. Some of the early studies with cats and non-human primates
(NHPs) are controversial for animal welfare reasons and are of questionable
clinical relevance, particularly with respect to the treatment of amblyopia. More
recently, the UK Home Office records have shown that attention is now more
focused on rodents, especially the mouse. This is likely to be due to the
perceived need for genetically-altered animals, rather than to knowledge of the
similarities and differences of vision in cats, NHPs and rodents, and the fact
that the same techniques can be used for all of the species. We discuss the
advantages and limitations of animal and non-animal methods for vision research,
and assess their relative contributions to basic knowledge and clinical practice,
as well as outlining the opportunities they offer for implementing the principles
of the Three Rs (Replacement, Reduction and Refinement).
PMID- 27494624
TI - More than 70 years of pyrogen detection: Current state and future perspectives.
AB - In the quality assurance of medical products, tests for sterility are essential.
For parenteral pharmaceuticals, avoiding the presence of pyrogens is crucial.
These fever-inducing substances (endotoxins and non-endotoxins) are not
eliminated by standard sterilisation processes, and are biologically active once
in the bloodstream, causing risks to human health, ranging from mild reactions
(e.g. fever) to septic shock and death. Therefore, for injectable formulations,
pyrogen testing is mandatory. Over the years, various pyrogen testing methods
have been introduced, namely: in the 1940s, the rabbit pyrogen test, which is an
in vivo test that measures the fever reaction as an endpoint; in the 1970s, the
Limulus Amoebocyte Lysate (LAL) test, which is an in vitro test (with the
haemolymph of the horseshoe crab) that specifically detects endotoxin; and in
2010, the Monocyte-Activation Test (MAT), which is a non-animal based in vitro
pyrogen test that represents a full replacement of the rabbit test. Due to the
ubiquity and biological significance of pyrogens, we are currently further
developing the MAT so that it can be used for other applications. More
specifically, our focus is on the detection of pyrogenic contamination on medical
devices, as well as on the measurement of air quality. In addition, further
improvements to permit the use of cryopreserved blood in the MAT, to overcome the
limitations in the availability of freshly-drawn blood from human donors, are
ongoing.
PMID- 27494625
TI - Evaluation of non-animal methods for assessing skin sensitisation hazard: A
Bayesian Value-of-Information analysis.
AB - This paper offers a Bayesian Value-of-Information (VOI) analysis for guiding the
development of non-animal testing strategies, balancing information gains from
testing with the expected social gains and costs from the adoption of regulatory
decisions. Testing is assumed to have value, if, and only if, the information
revealed from testing triggers a welfare-improving decision on the use (or non
use) of a substance. As an illustration, our VOI model is applied to a set of
five individual non-animal prediction methods used for skin sensitisation hazard
assessment, seven battery combinations of these methods, and 236 sequential 2
test and 3-test strategies. Their expected values are quantified and compared to
the expected value of the local lymph node assay (LLNA) as the animal method. We
find that battery and sequential combinations of non-animal prediction methods
reveal a significantly higher expected value than the LLNA. This holds for the
entire range of prior beliefs. Furthermore, our results illustrate that the
testing strategy with the highest expected value does not necessarily have to
follow the order of key events in the sensitisation adverse outcome pathway
(AOP).
PMID- 27494626
TI - Exploring waiving opportunities for mammalian acute systemic toxicity tests.
AB - A survey was carried out to explore opportunities for waiving mammalian acute
systemic toxicity tests. We were interested in finding out whether data from a
sub-acute toxicity test could be used to predict the outcome of an acute systemic
toxicity test. The survey was directed at experts in the field of toxicity
testing, and was carried out in the context of the upcoming 2018 final
registration deadline for chemicals under the EU REACH Regulation. In addition to
the survey, a retrospective data analysis of chemicals that had already been
registered with the European Chemicals Agency, and for which both acute and sub
acute toxicity data were available, was carried out. This data analysis was
focused on chemicals that were administered via the oral route. The answers to
the questionnaire showed a willingness to adopt waiving opportunities. In
addition, the responses showed that data from a sub-acute toxicity test or dose
range finding study might be useful for predicting chemicals that do not require
classification for acute oral toxicity (LD50 > 2000mg/kg body weight). However,
with the exception of substances that fall into the non-classified category, it
is difficult to predict current acute oral toxicity categories.
PMID- 27494627
TI - Local tolerance testing under REACH: Accepted non-animal methods are not on equal
footing with animal tests.
AB - In general, no single non-animal method can cover the complexity of any given
animal test. Therefore, fixed sets of in vitro (and in chemico) methods have been
combined into testing strategies for skin and eye irritation and skin
sensitisation testing, with pre-defined prediction models for substance
classification. Many of these methods have been adopted as OECD test guidelines.
Various testing strategies have been successfully validated in extensive in-house
and inter-laboratory studies, but they have not yet received formal acceptance
for substance classification. Therefore, under the European REACH Regulation,
data from testing strategies can, in general, only be used in so-called weight-of
evidence approaches. While animal testing data generated under the specific REACH
information requirements are per se sufficient, the sufficiency of weight-of
evidence approaches can be questioned under the REACH system, and further animal
testing can be required. This constitutes an imbalance between the regulatory
acceptance of data from approved non-animal methods and animal tests that is not
justified on scientific grounds. To ensure that testing strategies for local
tolerance testing truly serve to replace animal testing for the REACH
registration 2018 deadline (when the majority of existing chemicals have to be
registered), clarity on their regulatory acceptance as complete replacements is
urgently required.
PMID- 27494628
TI - Fine Mapping of Two Additive Effect Genes for Awn Development in Rice (Oryza
sativa L.).
AB - Awns, important domestication and agronomic traits in rice (Oryza sativa L.), are
conferred by polygenes and the environment. Near isogenic line (NIL) pairs BM33
and BM38 were constructed from crosses between awnless japonica cv Nipponbare as
recurrent parent, and lines SLG or Funingxiaohongmang (awned japonica
accessions), respectively, as donors. In order to study the genetic and molecular
mechanism of awning, two unknown, independent genes with additive effects were
identified in a cross between the NILs. To map and clone the two genes, a BC4F4
population of 8,103 individuals and a BC4F6 population of 11,206 individuals were
constructed. Awn3-1 was fine mapped to a 101.13 kb genomic region between Indel
marker In316 and SNP marker S9-1 on chromosome 3. Nine predicted genes in the
interval were annotated in the Rice Annotation Project Database (RAP-DB), and
Os03g0418600 was identified as the most likely candidate for Awn3-1 through
sequence comparisons and RT-PCR assays. Awn4-2 was fine mapped to a 62.4 kb
genomic region flanked by simple sequence repeat (SSR) marker M1126 and Indel
maker In73 on chromosome 4L. This region contained the previously reported gene
An-1 that regulates awn development. Thus, An-1 may be the candidate gene of Awn4
2. These results will facilitate cloning of the awn genes and thereby provide an
understanding of the molecular basis of awn development.
PMID- 27494629
TI - Safety and efficacy of extracorporeal shock wave therapy (ESWT) in calcinosis
cutis associated with systemic sclerosis.
AB - OBJECTIVES: Calcinosis cutis is a frequent, difficult to treat manifestation of
systemic sclerosis (SSc) associated with high morbidity. The aim of this
prospective, controlled, monocentric study was to assess safety and efficacy of
extracorporeal shock wave therapy (ESWT) for calcinosis cutis of the finger in
SSc patients. METHODS: A 12-week proof of concept study in which 4 SSc patients
with calcinosis cutis were treated at one painful finger with high-energy,
focused ESWT, in 3 sessions with one-week interval between each session. A
second, untreated finger, served as control. The outcome parameters were: change
in pain, change in size of calcification measured by ultrasound (US) and computed
tomography (CT) and of the force by pressing the finger against a Dolorimeter.
RESULTS: Pain was reduced (by 91% and 60%) in the treated finger in two out of
four patients. There was no change in the control fingers. The size of the
calcinosis in the treated finger was reduced in three (US) and four patients
(CT). Inter-assessor agreement was acceptable for US volume measures (ICC=0.863).
CONCLUSIONS: We could show promising evidence for safety and efficacy of ESWT for
chronic, treatment resistant calcinosis cutis in SSc patients, thus justifying
the initiation of larger multicentre controlled trials.
PMID- 27494630
TI - Influenza immunization during pregnancy: Benefits for mother and infant.
AB - The serious consequences of influenza infection during pregnancy have been
recognized for almost a century. In this article, we reviewed the evidence on the
immunogenicity, safety and impact of maternal influenza immunization for both
mother and child. After vaccination, pregnant women have similar protective
titers of anti-influenza antibodies as non-pregnant women, demonstrating that
pregnancy does not alter the trivalent inactivated influenza vaccine immune
response. Studies from the United States, Europe and resource-constrained regions
demonstrate that maternal vaccination is associated with increased anti-influenza
antibody concentrations and protection in the newborn child as well as the
immunized mother. Given the acceptable safety profile of influenza vaccines and
the World Health Organization's recommendation for its use in pregnant women,
maternal vaccination with inactivated influenza vaccine is a cost-effective
approach to decrease influenza disease in newborns. However, as seen for
influenza immunization in the elderly, the protective efficacy of current
inactivated vaccines in protection of newborns is 50% at best, indicating
significant room for vaccine improvement, which could potentially be achieved by
addition of a safe and effective adjuvant. Thus, global deployment of inactivated
influenza immunization during pregnancy would have substantial and measurable
health benefits for mothers and their newborns.
PMID- 27494632
TI - Rapid electrostatics-assisted layer-by-layer assembly of near-infrared-active
colloidal photonic crystals.
AB - Here we report a rapid and scalable bottom-up technique for layer-by-layer (LBL)
assembling near-infrared-active colloidal photonic crystals consisting of large
(?1MUm) silica microspheres. By combining a new electrostatics-assisted colloidal
transferring approach with spontaneous colloidal crystallization at an air/water
interface, we have demonstrated that the crystal transfer speed of traditional
Langmuir-Blodgett-based colloidal assembly technologies can be enhanced by nearly
2 orders of magnitude. Importantly, the crystalline quality of the resultant
photonic crystals is not compromised by this rapid colloidal assembly approach.
They exhibit thickness-dependent near-infrared stop bands and well-defined Fabry
Perot fringes in the specular transmission and reflection spectra, which match
well with the theoretical calculations using a scalar-wave approximation model
and Fabry-Perot analysis. This simple yet scalable bottom-up technology can
significantly improve the throughput in assembling large-area, multilayer
colloidal crystals, which are of great technological importance in a variety of
optical and non-optical applications ranging from all-optical integrated circuits
to tissue engineering.
PMID- 27494633
TI - Dissecting Embryonic Stem Cell Self-Renewal and Differentiation Commitment from
Quantitative Models.
AB - To model quantitatively embryonic stem cell (ESC) self-renewal and
differentiation by computational approaches, we developed a unified mathematical
model for gene expression involved in cell fate choices. Our quantitative model
comprised ESC master regulators and lineage-specific pivotal genes. It took the
factors of multiple pathways as input and computed expression as a function of
intrinsic transcription factors, extrinsic cues, epigenetic modifications, and
antagonism between ESC master regulators and lineage-specific pivotal genes. In
the model, the differential equations of expression of genes involved in cell
fate choices from regulation relationship were established according to the
transcription and degradation rates. We applied this model to the Murine ESC self
renewal and differentiation commitment and found that it modeled the expression
patterns with good accuracy. Our model analysis revealed that Murine ESC was an
attractor state in culture and differentiation was predominantly caused by
antagonism between ESC master regulators and lineage-specific pivotal genes.
Moreover, antagonism among lineages played a critical role in lineage
reprogramming. Our results also uncovered that the ordered expression alteration
of ESC master regulators over time had a central role in ESC differentiation
fates. Our computational framework was generally applicable to most cell-type
maintenance and lineage reprogramming.
PMID- 27494634
TI - Development and evaluation of a school-based asthma educational program.
AB - OBJECTIVES: To develop, implement, and evaluate the effects of a school-based
asthma educational program on Saudi primary school teachers' asthma awareness and
competence in delivering asthma-related first aid interventions. METHODS: An
asthma educational intervention program entitled "School Asthma Action Program"
(SAAP) was designed based on pedagogical principles and implemented among
teachers randomly selected from girls' primary schools in Riyadh, Saudi Arabia.
This pilot study employed a pre-test/post-test experimental design. A previously
tested asthma awareness questionnaire and a custom-designed asthma competence
score sheet were used to evaluate the effects of the educational intervention
program on teacher's asthma awareness and competence in providing asthma-related
first aid interventions at schools. RESULTS: Forty-seven teachers from five
different primary schools participated in the program. Of the 47 teachers, 39
completed both the pre- and post-program questionnaires. The SAAP improved
teachers' awareness of asthma (teachers' median pre-program score was 11 (range 5
18) and their post-program score was 15 (range 7-18), p < 0.001) and their
attitudes toward asthma management at schools (teachers' median pre-program score
was 74 (range 15-75) and their post-program score was 75 (range 15-75), p =
0.043). Further, it improved teachers' competence in providing asthma-related
first aid interventions (teachers' mean pre-program score was 1.4 +/- 2.3 and
their mean post-program score was 9.8 +/- 0.5, p < 0.001). After completing the
SAAP, a high proportion of teachers reported increased confidence in providing
care to children with asthma at school. CONCLUSION: School-based asthma
educational programs can significantly improve teachers' knowledge of asthma and
their competence in providing asthma-related first aid interventions during
emergencies.
PMID- 27494635
TI - Bonding, Luminescence, Metallophilicity in Linear Au3 and Au2Ag Chains Stabilized
by Rigid Diphosphanyl NHC Ligands.
AB - The heterofunctional and rigid ligand N,N'-diphosphanyl-imidazol-2-ylidene
(PCNHCP; P = P(t-Bu)2), through its phosphorus and two N-heterocyclic carbene
(NHC) donors, stabilizes trinuclear chain complexes, with either Au3 or AgAu2
cores, and dinuclear Au2 complexes. The two oppositely situated PCNHCP (L)
ligands that "sandwich" the metal chain can support linear and rigid structures,
as found in the known tricationic Au(I) complex [Au3(MU3
PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)3 (OTf = CF3SO3; [Au3L2](OTf)3; Chem.
Commun. 2014, 50, 103-105) now also obtained by transmetalation from [Ag3(MU3
PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)3 ([Ag3L2](OTf)3), or in the mixed-metal
tricationic [Au2Ag(MU3-PCNHCP,kappaP,kappaCNHC,kappaP)2](OTf)3 ([Au2AgL2](OTf)3).
The latter was obtained stepwise by the addition of AgOTf to the digold(I)
complex [Au2(MU2-PCNHCP,kappaP,kappaCNHC)2](OTf)2 ([Au2L2](OTf)2). The latter
contains two dangling P donors and displays fluxional behavior in solution, and
the Au...Au separation of 2.8320(6) A in the solid state is consistent with
metallophilic interactions. In the solvento complex [Au3Cl2(tht)(MU3
PCNHCP,kappaP,kappaCNHC,kappaP)](OTf).MeCN ([Au3Cl2(tht)L](OTf).MeCN), which
contains only one L and one tht ligand (tht = tetrahydrothiophene), the metal
chain is bent (148.94(2) degrees ), and the longer Au...Au separation (2.9710(4)
A) is in line with relaxation of the rigidity due to a more "open" structure.
Similar features were observed in [Au3Cl2(SMe2)L](OTf).2MeCN. A detailed study of
the emission properties of [Au3L2](OTf)3, [Au3Cl2(tht)L](OTf).MeCN,
[Au2L2](OTf)2, and [Au2AgL2](OTf)3 was performed by means of steady state and
time-resolved photophysical techniques. The complex [Au3L2](OTf)3 displays a
bright (photoluminescence quantum yield = 80%) and narrow emission band centered
at 446 nm with a relatively small Stokes' shift and long-lived excited-state
lifetime on the microsecond timescale, both in solution and in the solid state.
In line with the very narrow emission profile centered in the violet-blue region,
fabrication of organic light-emitting devices (OLEDs) comprising the
[Au3L2](OTf)3 complex demonstrated its usefulness as a deep-blue emitter in
solution-processed OLEDs. Electrochemical and Raman spectroscopic studies were
also performed on [Au3L2](OTf)3. Experimental results were rationalized by means
of Wave-Function Theory (WFT) and Density Functional Theory (DFT). MP2
calculations gave a satisfactory description of the structures of the cationic
complexes [Au3L2](3+) and [Au2L2](2+) and pointed to Au...Au interactions having
an electrostatic component owing to the dissimilar charge distribution in the
chain caused by the heterofunctional ligand. The nature of the emitting states
and their geometric distortions relative to the ground states in [Au3L2](3+) and
[Au2L2](2+) was studied by DFT, revealing contraction of the Au...Au distances
and coordination geometry changes by association of the dangling P donor,
respectively.
PMID- 27494631
TI - Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal
Cancers.
AB - SIGNIFICANCE: Gastrointestinal (GI) cancer taken together constitutes one of the
most common cancers worldwide with a broad range of etiological mechanisms. In
this review, we have examined the impact of nitric oxide (NO) on the etiology of
colon, colorectal, gastric, esophageal, and liver cancers. Recent Advances:
Despite differences in etiology, initiation, and progression, chronic
inflammation has been shown to be a common element within these cancers showing
interactions of numerous pathways. NO generated at the inflammatory site
contributes to the initiation and progression of disease. The amount of NO
generated, time, and site vary and are an important determinant of the biological
effects initiated. Among the nitric oxide synthase enzymes, the inducible isoform
has the most diverse range, participating in numerous carcinogenic processes.
There is emerging evidence showing that inducible nitric oxide synthase (NOS2)
plays a central role in the process of tumor initiation and/or development.
CRITICAL ISSUES: Redox inflammation through NOS2 and cyclooxygenase-2
participates in driving the mechanisms of initiation and progression in GI
cancers. FUTURE DIRECTIONS: Understanding the underlying mechanism involved in
NOS2 activation can provide new insights into important prevention and treatment
strategies. Antioxid. Redox Signal. 26, 1059-1077.
PMID- 27494636
TI - Variation in ruminal in situ degradation of crude protein and starch from maize
grains compared to in vitro gas production kinetics and physical and chemical
characteristics.
AB - The objectives of this study were (1) to evaluate in situ ruminal dry matter
(DM), crude protein (CP) and starch degradation characteristics and in vitro gas
production (GP) kinetics using a set of 20 different maize grain genotypes and
(2) to predict the effective degradation (ED) of CP and starch from chemical and
physical characteristics alone or in combination with in vitro GP measurements.
Maize grains were characterised by different chemical and physical
characteristics. Ruminal in situ degradation was measured in three lactating
Jersey cows. Ground grains (sieve size: 2 mm) were incubated in bags for 1, 2, 4,
8, 16, 24, 48 and 72 h. Bag residues were analysed for CP and starch content.
Degradation kinetics was determined and the ED of DM, CP and starch calculated
using a ruminal passage rate of 5%/h and 8%/h. The GP of the grains (sieve size:
1 mm) was recorded after 2, 4, 6, 8, 12, 24, 48 and 72 h incubation in buffered
rumen fluid and fitted to an exponential equation to determine GP kinetics.
Correlations and stepwise multiple linear regressions were evaluated for the
prediction of ED calculated for a passage rate of 5%/h (ED5) for CP (EDCP5) and
starch (EDST5). The in situ parameters and ED5 varied widely between genotypes
with average values (+/-SD) of 64% +/- 4.2, 62% +/- 4.1 and 65% +/- 5.2 for ED5
of DM, EDCP5 and EDST5 and were on average 10 percentage points lower for a
passage rate of 8%/h. Degradation rates varied between 4.8%/h and 7.4%/h, 4.1%/h
and 6.5%/h and 5.3%/h and 8.9%/h for DM, CP and starch, respectively. These rates
were in the same range as GP rates (6.0-8.3%/h). The EDCP5 and EDST5 were related
to CP concentration and could be evaluated in detail using CP fractions and
specific amino acids. In vitro GP measurements and GP rates correlated well with
EDCP5 and EDST5 and predicted EDCP5 and EDST5 in combination with the chemical
characteristics of the samples. Equations can be used to obtain quick and cost
effective information on ruminal degradation of CP and starch from maize grains.
PMID- 27494637
TI - Nutritional value of raw and micronised field beans (Vicia faba L. var. minor)
with and without enzyme supplementation containing tannase for growing chickens.
AB - An experiment examined the effects of two field bean cultivar samples with
different tannin contents, the effect of heat treatment (micronising) and the
effect of dietary supplementation of a proprietary enzyme preparation containing
tannase, pectinase, and xylanase activities on metabolisable energy (ME), total
tract dry matter digestibility (DMD) and ether extract digestibility (EED),
nitrogen retention (NR), tannin degradability, gastrointestinal tract (GIT)
development, and endogenous mucin losses excretion in broiler chickens. The
Control diet contained per kg 221 g crude protein and 12.83 MJ ME. Four
additional diets contained 300 g/kg of each of the two untreated or micronised
experimental field bean cultivar samples. Each diet was then split into two
batches and one of them was supplemented with 3400 units tannase per kg diet
resulting in 10 diets in total. Each diet was fed to seven pens with two randomly
selected male broilers each. Birds fed the high tannin bean sample had a lower
weight gain (p < 0.001), and a lower determined apparent ME (p < 0.05), and DMD
(p < 0.001) but a higher tannin degradability (p < 0.001). Compared to the
Control diet, feeding field beans increased (p < 0.001) the weights of the
proventriculus and gizzard of the birds, and also increased endogenous mucin
losses (p < 0.05). Supplementing diets with the tannase-containing enzyme
preparation improved dietary ME (p < 0.001), DMD (p < 0.001), NR (p < 0.001) and
DEE (p < 0.05), but did not change tannin degradability. Heat treatment of the
beans reduced the degradability of condensed tannins and increased endogenous
mucin losses (p < 0.05). The differences in the feeding value of the different
field bean samples were not improved by heat treatment, but enzyme
supplementation improved the feeding value of all diets regardless of the bean
samples or heat treatment. Further research is warranted to study the
effectiveness of tannase supplementation in poultry diet formulations by dose
response trials with purified tannase preparations.
PMID- 27494638
TI - Effect of dietary supplementation of gallic acid on nitrogen balance, nitrogen
excretion pattern and urinary nitrogenous constituents in beef cattle.
AB - The objective of the trial was to study the effects of dietary supplementation of
gallic acid (GA) on nitrogen (N) balance, N excretion pattern and urinary N
constituents in beef cattle. In a 4 * 4 Latin square design, four male 30-month
old Simmental cattle (443 +/- 22 kg live weight) received four levels of GA
(purity >= 98.5%), i.e. 0, 5.3, 10.5, 21.1 g/kg DM, added to a basal ration. Each
experimental period lasted 17 d, consisting of 12 d adaptation and 5 d sampling.
The results showed that supplementation of GA at 5.3, 10.5 or 21.1 g/kg DM did
not affect the N balance but regulated the N excretion pattern by increasing the
ratio of faecal N/urinary N and decreasing the ratio of urinary urea N/total
urinary N in beef cattle fed at maintenance level.
PMID- 27494639
TI - Nonlinear Refractory Plasmonics with Titanium Nitride Nanoantennas.
AB - Titanium nitride (TiN) is a novel refractory plasmonic material which can sustain
high temperatures and exhibits large optical nonlinearities, potentially opening
the door for high-power nonlinear plasmonic applications. We fabricate TiN
nanoantenna arrays with plasmonic resonances tunable in the range of about 950
1050 nm by changing the antenna length. We present second-harmonic (SH)
spectroscopy of TiN nanoantenna arrays, which is analyzed using a nonlinear
oscillator model with a wavelength-dependent second-order response from the
material itself. Furthermore, characterization of the robustness upon strong
laser illumination confirms that the TiN antennas are able to endure laser
irradiation with high peak intensity up to 15 GW/cm(2) without changing their
optical properties and their physical appearance. They outperform gold antennas
by one order of magnitude regarding laser power sustainability. Thus, TiN
nanoantennas could serve as promising candidates for high-power/high-temperature
applications such as coherent nonlinear converters and local heat sources on the
nanoscale.
PMID- 27494640
TI - Electronically Excited States of Borylenes.
AB - Borylenes, RB, are elusive reactive intermediates. Still not much is known about
their excited states from spectroscopic experiments, and existing knowledge is
limited to diatomic borylenes only. The electronic structure and geometry of
borylenes with diverse substituents on boron (where R = H, F, Cl, CH3, CF3, tBu,
NH2, Ph, and SiMe3) were studied by means of computational chemistry. For this
purpose, geometries of borylenes in their lowest singlet and triplet states were
optimized at the B3LYP/def2-TZVP level of theory. Additionally, the influence of
substitution on the energies of frontier molecular orbitals, HOMO-LUMO energy
gaps, singlet-triplet energy splittings, and excitation energies was
investigated. Two lowest vertical singlet-singlet excitations were computed using
EOM-CCSD and TD-DFT (using hybrid B3LYP, and long-range separated CAM-B3LYP and
omegaB97X functionals) in combination with the aug-cc-pVTZ basis set. The
electronic transitions involve excitations from nonbonding sp boron orbital
(HOMO) mainly to empty p(B) orbitals and partially to the orbitals of the
substituent, and are of n -> pi* type. The results can facilitate prospective
identification of borylenes, e.g., in UV-vis matrix isolation or time-resolved
spectroscopy experiments.
PMID- 27494641
TI - The effect of subchronic supplementation with folic acid and l-arginine on
homocysteine-induced seizures.
AB - The aim of the present study was to examine the effect of subchronic co
administration of folic acid (F) and l-arginine (A) on behavioural and
electroencephalographic (EEG) characteristics of dl homocysteine thiolactone (H)
induced seizures in adult rats. The activity of membrane ATPases in different
brain regions were also investigated. Rats were treated with F, A, or vehicle for
15 days (regimen: F 5 mg/kg + A 500 mg/kg (F5A500); F 10 mg/kg + A 300 mg/kg
(F10A300)). Seizures were elicited by convulsive dose of H (H, F5A500H, F10A300H)
Subchronic supplementation with F and A did not affect seizure incidence, number
of seizure episodes, and severity in F5A500H and F10A300H groups vs. H group.
However, a tendency to increase latency and decrease the number of seizure
episodes was noticed in the F10A300H group. EEG mean spectral power densities
during ictal periods were significantly lower in F10A300H vs. H group. The
activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost
all examined structures in rats treated with F and A. We can conclude that
subchronic supplementation with folic acid and l-arginine has an antiepileptic
effect in dl homocysteine thiolactone induced epilepsy.
PMID- 27494642
TI - Low-temperature SCR of NOx by NH3 over MnOx/SAPO-34 prepared by two different
methods: a comparative study.
AB - The low-temperature selective catalytic reduction (SCR) of NOx is a promising
technology for removing NOx from flue gases. However, the vulnerability of Mn
based catalysts to SO2 and H2O poisoning makes them unsuitable for industrial
application. Herein, catalysts based on the MnOx/SAPO-34 catalysts were prepared
by conventional impregnation and an improved molecularly designed dispersion
method for use in the low-temperature SCR. The improved molecularly designed
catalyst containing 20 wt% of MnOx exhibited high low-temperature NH3-SCR
activity. Nearly 90% of the NOx was converted exclusively to N2 at 160 degrees C
using this catalyst. The structure and morphological analyses of the catalyst
showed that the amorphous MnOx was well dispersed on the surface of the support.
The reasons for the high performance of the catalysts were ascertained using
surface N2 adsorption, XPS, H2-TPR and NH3-TPD. The results of these analyses
indicated that high specific surface area and the redox capability, of the
abundant Mn4+ and Mn3+ species, coupled with the surface chemisorbed oxygen and
strong acid sites had a significant effect on the SCR reaction. In addition, the
effects of SO2 and H2O on activity of the catalysts were also investigated and it
was found that the highly dispersed 20 wt% MnOx/SAPO-34 catalyst exhibited better
SO2 poisoning resistance than the other impregnated catalysts.
PMID- 27494643
TI - Perceptions of orthodontic specialist training in the United Kingdom: a national
survey of postgraduate orthodontic student opinion.
AB - INTRODUCTION: Postgraduate orthodontic education is highly challenging. There is
a lack of evidence regarding orthodontic postgraduates' perceptions of their
orthodontic education in the United Kingdom. In addition, no study has been
conducted to compare the postgraduate orthodontic training experience between UK
trainees and international postgraduates. OBJECTIVES: (1) To investigate
orthodontic UK trainees' and international postgraduates' perception and
satisfaction of their orthodontic education. (2) To compare postgraduate
orthodontic training experience between UK trainees and international
postgraduates. (3) To compare orthodontic caseload between UK trainees and
international postgraduates. METHODS: Utilizing a descriptive, cross-sectional
survey, conducted through a web-based self-administered questionnaire, the sample
population consisted of all 189 orthodontic postgraduates in the United Kingdom.
RESULTS: One hundred and twenty-five questionnaires were completed resulting in a
response rate of 66.1%. All three academic years were evenly represented. Ninety
five (76%) respondents rated the quality of their postgraduate orthodontic
education as excellent. Over 90% of third year postgraduates felt the quality of
their education was excellent. The majority of orthodontic trainees (n = 98,
78.4%) were satisfied with the number of cases. Apart from the first year
postgraduates, other postgraduates regardless of UK trainee or international
postgraduate status reported a high number of cases in treatment, with 45 (36%)
respondents treating more patients than the recommended range of 80-120.
Postgraduates' responses were less positive regarding their ability to influence
the delivery of their programme, whether their programme represented value for
money and the fairness of their training. Most of the respondents believed that
UK trainees had an advantage in communicating with patients. CONCLUSION: The
majority of orthodontic postgraduates rated the quality of their postgraduate
education as excellent. Apart from first year postgraduates, other postgraduates
irrespective of UK trainee or international postgraduate status reported a high
number of cases in treatment. There was no difference in caseload between UK
trainee and international postgraduate groups.
PMID- 27494644
TI - A pilot study of cardiac electrophysiology catheters to map and pace bladder
electrical activity.
AB - AIMS: This is a pilot study to evaluate the feasibility of using diagnostic
cardiac electrophysiology catheters for recording intrinsic urinary bladder
electrical activity and for electrical pacing capture of bladder tissue. METHODS:
During cystoscopy, a curved quadripolar catheter was introduced and contact was
made with the right and left halves of the dome and trigone in adult female
patients undergoing cystoscopy. Electrical activity was recorded, using a
commercially available cardiac electrophysiologic recording system, before and
during pacing at 0.5-3.0 Hz. RESULTS: Apparent spontaneous electrical
depolarizations were detected in both the trigone and the dome. The amplitude of
these depolarizations was in the microVolt range. During pacing, local electrical
capture was noted in the trigone, but not in the dome. CONCLUSIONS: Spontaneous
low-amplitude electrical activity was detected in the bladder through the use of
commercially available cardiac electrophysiology equipment. While these low-level
signals could represent noise, the voltage, and morphology resemble detrusor
muscle action potentials previously seen in animal studies. Pacing induced local
electrical capture in the trigone but not the dome.
PMID- 27494645
TI - Microwave treatment of dairy manure for resource recovery: Reaction kinetics and
energy analysis.
AB - A newly designed continuous-flow 915 MHz microwave wastewater treatment system
was used to demonstrate the effectiveness of the microwave enhanced advanced
oxidation process (MW/H2O2-AOP) for treating dairy manure. After the treatment,
about 84% of total phosphorus and 45% of total chemical oxygen demand were
solubilized with the highest H2O2 dosage (0.4% H2O2 per %TS). The reaction
kinetics of soluble chemical oxygen demand revealed activation energy to be in
the range of 5-22 kJ mole-1. The energy required by the processes was
approximately 0.16 kWh per liter of dairy manure heated. A higher H2O2 dosage
used in the system had a better process performance in terms of solids
solubilization, reaction kinetics, and energy consumption. Cost-benefit analysis
for a farm-scale MW/H2O2-AOP treatment system was also presented. The results
obtained from this study would provide the basic knowledge for designing an
effective farm-scale dairy manure treatment system.
PMID- 27494646
TI - Motives underlying smoking in college students with ADHD.
AB - BACKGROUND: The positive association between attention deficit hyperactivity
disorder (ADHD) symptoms and smoking in youth has been well documented. Less
research has examined why individuals with ADHD, particularly college students,
are at increased risk for smoking. OBJECTIVES: This longitudinal study examined
whether smoking motives [cognitive enhancement, tolerance, negative reinforcement
(smoking to reduce negative affect or stress), craving, social influences, and
weight control] helped to explain the relation between ADHD symptoms (inattention
and hyperactivity/impulsivity) and cigarette smoking among college students.
METHODS: Participants were 889 undergraduates (21% men) and their parents who
completed online surveys at the beginning and end of the Fall semester regarding
their smoking behaviors, ADHD symptoms, and smoking motives. Structural equation
modeling was used to analyze data and answer research questions. RESULTS:
Nineteen percent of students reported smoking, while 20% reported one or more
inattentive symptoms, 35% reported one or more hyperactive/impulsive symptoms,
and 3.3% met criteria for ADHD. All smoking motives significantly moderated the
relation between inattentive symptoms and smoking, while most smoking motives
(negative reinforcement, tolerance, craving, cognitive enhancement, and weight
control) moderated the link between hyperactive/impulsive symptoms and smoking.
Results remained significant after controlling for stimulant medication use and
conduct disorder symptoms. Conclusions/Importance. Addressing negative
reinforcement, craving, social influences, and tolerance in prevention and
intervention efforts on college campuses may reduce smoking. Results also
highlight the importance of assessing a range of ADHD symptoms in college
students as ADHD symptoms, even at subthreshold levels, were associated with
increased smoking rates among college students.
PMID- 27494647
TI - Effects of active pause pattern of surface electromyographic activity among
subjects performing monotonous tasks: A systematic review.
AB - Active pauses have shown potentially beneficial effects to increase the
variability of the electrical activation pattern of muscles. However, there is a
lack of consensus as to how to design and implement those pauses and the
processing methods of surface electromyography (EMG) data when evaluating low
level monotonous tasks. The aim of this systematic review was to synthesize the
evidences regarding the way which active pauses have been applied, and the
methods used to investigate the related EMG changes. PubMed-MEDLINE, Embase, Web
of Science, Lilacs, Ebsco, and Scopus databases were searched. Two authors
independently extracted data from the primary studies. The methodological quality
was assessed using a list from van der Windt et al. (2000), and the level of
evidence was synthesized through GRADE. The ISEK guideline for reporting EMG data
was also applied as a checklist. Fifteen studies were included - 14 with high
methodological quality. In general, active pauses were able to change the level
of EMG activity in monotonous tasks. The level of evidence through GRADE was very
low for all EMG processing methods, except RMS which was low. A vast
heterogeneity concerning the methods applied to analyze EMG data contributed to
decrease the quality of evidence synthesis, and the findings need to be carefully
considered. The GRADE approach and the ISEK guideline contributed to identify
important flaws in the literature. Future studies investigating active pauses in
longitudinal studies and following the standard for recording and reporting EMG
data care are warranted.
PMID- 27494648
TI - BRAF and MEK inhibitors in pediatric glioma: new therapeutic strategies, new
toxicities.
AB - INTRODUCTION: BRAF mutation was initially reported in metastatic melanomas, and
more recently in a variety of human cancers. BRAF acts as a down-stream effector
of growth factor signaling leading to cell cycle progression, proliferation and
survival. Development of selective inhibitors of BRAF has improved the survival
of patients with melanoma and offers potential new therapeutic strategy in
children with BRAF-mutant glioma. Areas covered: Mechanisms of resistance to BRAF
inhibitors have recently been described as due to the paradoxical activation of
the MAPK pathway. Combination therapy with BRAF and MEK inhibition has proved
capable of overcoming the resistance with effective results in patients with
melanoma. Prospective studies in pediatric glioma are warranted. Combination
therapy has a different toxicity profile compared to BRAF inhibitor alone. Herein
we review the state-of-the-art of toxicities associated with these agents, with a
special focus on children. Expert opinion: Some toxicities appear more specific
to adults, due to a combination of factors, such as patient age and predisposing
risk factors. Moreover, it is recommended that the co-administration of BRAF
inhibitors and drugs metabolized by the cytochrome P450 system in the liver be
avoided, as this can lead to significant complications secondary to
pharmacological interactions.
PMID- 27494649
TI - Behavior of Photocarriers in the Light-Induced Metastable State in the p-n
Heterojunction of a Cu(In,Ga)Se2 Solar Cell with CBD-ZnS Buffer Layer.
AB - We fabricated Cu(In,Ga)Se2 (CIGS) solar cells with a chemical bath deposition
(CBD)-ZnS buffer layer grown with varying ammonia concentrations in aqueous
solution. The solar cell performance was degraded with increasing ammonia
concentration, due to actively dissolved Zn atoms during CBD-ZnS precipitation.
These formed interfacial defect states, such as hydroxide species in the CBD-ZnS
film, and interstitial and antisite Zn defects at the p-n heterojunction. After
light/UV soaking, the CIGS solar cell performance drastically improved, with a
rise in fill factor. With the Zn-based buffer layer, the light soaking treatment
containing blue photons induced a metastable state and enhanced the CIGS solar
cell performance. To interpret this effect, we suggest a band structure model of
the p-n heterojunction to explain the flow of photocarriers under white light at
the initial state, and then after light/UV soaking. The determining factor is a
p+ defect layer, containing an amount of deep acceptor traps, located near the
CIGS surface. The p+ defect layer easily captures photoexcited electrons, and
then when it becomes quasi-neutral, attracts photoexcited holes. This alters the
barrier height and controls the photocurrent at the p-n junction, and fill factor
values, determining the solar cell performance.
PMID- 27494650
TI - Formulation and evaluation of novel controlled release of topical pluronic
lecithin organogel of mefenamic acid.
AB - In the present study, pluronic lecithin based organogels (PLO gels) were
formulated as topical carrier for controlled delivery of mefenamic acid. Ten
organogel formulations were prepared by a method employing lecithin as lipophilic
phase and pluronic F-127 as hydrophilic phase in varying concentrations to study
various parameters using in vitro diffusion study and in vivo studies. All
formulations were found to be off-white, homogenous, and reluctant to be washed
easily and have pH value within the range of 5.56-5.80 which is nonirritant.
Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to
F10 (pluronic) resulted in decrease of the gelation temperature, increase of
viscosity and reduction of spreadability of gels having polymer tendency to form
rigid 3D network. Organogels with higher viscosity were found to be more stable
and retard the drug release from the gel. The formulations of F2 and F3 were
selected for kinetic studies and stability studies, as they found to have all
physical parameters within acceptable limits, highest percent drug content and
exhibited highest drug release in eight hours. The order of drug release from
various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7
> F6. The optimized formulation F2 was found to follow zero order rate kinetics
showing controlled release of the drug from the formulations. In vivo anti
inflammatory activity of optimized mefenamic acid organogel (F2) against a
standard marketed preparation (Volini gel) was found satisfactory and
significant.
PMID- 27494652
TI - Femtomolar Detection of Silver Nanoparticles by Flow-Enhanced Direct-Impact
Voltammetry at a Microelectrode Array.
AB - We report the femtomolar detection of silver (Ag) nanoparticles by direct-impact
voltammetry. This is achieved through the use of a random array of
microelectrodes (RAM) integrated into a purpose-built flow cell, allowing
combined diffusion and convection to the electrode surface. A coupled RAM-flow
cell system is implemented and is shown to give reproducible wall-jet type flow
characteristics, using potassium ferrocyanide as a molecular redox species. The
calibrated flow system is then used to detect and quantitatively size Ag
nanoparticles at femtomolar concentrations. Under flow conditions, it is found
the nanoparticle impact frequency increases linearly with the volumetric flow
rate. The resulting limit of detection is more than 2 orders of magnitude smaller
than the previous detection limit for direct-impact voltammetry (900 fM) [J.
Ellison et al. Sens. Actuators, B 2014, 200, 47], and is more than 30 times
smaller than the previous detection limit for mediated-impact voltammetry (83 fM)
[T. M. Alligrant et al. Langmuir 2014, 30, 13462].
PMID- 27494651
TI - NPR3 protects cardiomyocytes from apoptosis through inhibition of cytosolic BRCA1
and TNF-alpha.
AB - Natriuretic peptide receptor 3 (NPR3) is a clearance receptor by binding and
internalizing natriuretic peptides (NPs) for ultimate degradation. Patients with
cardiac failure show elevated NPs. NPs are linked to poor long-term survival
because of their apoptotic effects. However, the underling mechanisms have not
been identified yet. Here we report the role of NPR3 in anti-apoptosis via the
breast cancer type 1 susceptibility protein (BRCA1) and tumor necrosis factor
alpha (TNF-alpha ). To demonstrate a role for NPR3 in apoptosis, stable H9C2
cardiomyocyte cell lines using shRNA to knockdown NPR3 were generated. The
activities of caspase-3, 8, and 9 were significantly increased in NPR3 knockdown
H9C2 cardiomyocytes. Knockdown of NPR3 increased the expression of BRCA1. Also
NPR3 knockdown remarkably increased the activity of cAMP response element-binding
protein (CREB), a positive regulatory element for BRCA1 expression. BRCA1 showed
dispersed nuclear localization in non-cardiomyocytes while predominantly
cytoplasmic localization in H9C2 cells. Meanwhile, NPR3 knockdown significantly
increased TNF-alpha gene expression. These data show that NPR3 knockdown in H9C2
cells triggered both extrinsic and intrinsic apoptotic pathways. NPR3 protects
cardiomyocytes from apoptosis through inhibition of cytosolic BRCA1 and TNF
alpha, which are regulators of apoptosis. Our studies demonstrate anti-apoptosis
role of NPR3 in protecting cardiomyocytes and establish the first molecular link
between NP system and programmed cell death.
PMID- 27494653
TI - Tradeoffs of strategically reconnecting rivers to their floodplains: The case of
the Lower Illinois River (USA).
AB - During the latter half of the 19th Century and first half of the 20th Century,
the Illinois River was heavily altered through leveeing off large portions of its
floodplain, draining wetlands, and the construction of dams and river-training
structures that facilitated navigation. As a result of these alterations, flood
stages continue to rise, increasing flood risk and threatening to overtop levees
along the La Grange Segment (LGS) of the Illinois River. Over the last two
decades, more emphasis has been placed on reconnecting portions of floodplains to
rivers in order to solve the long-term problem of rising flood heights attributed
to continual heightening of levees to provide flood protection. Multiple studies
have suggested that strategically reconnecting larger portions of the LGS could
result in more sustainable floodplain management. However, the true costs and
benefits of reconnecting the floodplain are not known. We use a novel
hydrodynamic, geospatial, economic, and habitat suitability framework to assess
the tradeoffs of strategically reconnecting the Illinois River to its floodplain
in order to decrease flood risk, improve floodplain habitats, and limit the costs
of reconnection. Costs include building-associated losses, lost agricultural
profits, and levee removal and construction costs. Tested scenarios demonstrate
that while flood heights and environmental benefits are maximized through the
most aggressive levee setbacks and removals, these scenarios also have the
highest costs. However, the tradeoff of implementing lower-cost scenarios is that
there is less flood-height reduction and less floodplain habitat available.
Several individual levee districts have high potential for reconnection based on
limiting potential damages as well as providing floodplain habitat. To implement
large-scale strategic floodplain reconnection, costs range from $1.2-$4.3
billion. As such, payments for ecosystem services will likely be necessary to
compensate landowners for decreased long-term agricultural production and
building losses that result in flood-reduction benefits and increased floodplain
habitat.
PMID- 27494654
TI - Testing approaches for calculating stomatal ozone fluxes from passive samplers.
AB - Current ozone (O3) levels are high enough to negatively affect vegetation and may
become worse in the future. Ozone risk assessments have recently shifted from
exposure-based to flux-based metrics. Modeling stomatal O3 fluxes requires hourly
O3 and meteorological data, which are not always available. Large datasets of O3
concentrations measured with passive samplers exist worldwide, and usually
provide weekly to monthly means. We tested the suitability of using aggregated
data instead of hourly data for O3 flux calculations with 3-year time series of
O3 data from 24 Spanish air quality stations. Five different approaches and three
different parameterizations were tested. Ozone-averaged values in combination
with hourly meteorological data provided the most robust estimates of accumulated
O3 fluxes (Phytotoxic Ozone Dose with no threshold, POD0), and the median of the
absolute percent error (MAPE) due to aggregation came close to 5%. Aggregations
from 1week to 1month yielded similar errors, which is important in the cost
efficiency terms of the chosen passive sampler exposure periodicity. One major
limitation of these approaches is that they are not suitable for high POD
thresholds, and that accuracy of the measurements with passive samplers has to be
strictly assured in order to finally obtain acceptable errors. A combination of
meteorological data and O3 passive sampler measurements may be used to estimate
O3 fluxes at remote forest sites as a valuable risk assessment tool.
PMID- 27494655
TI - Temporal variation of sedimentation rates and potential factors influencing those
rates over the last 100years in Bohai Bay, China.
AB - Fourteen sediment cores were collected from Bohai Bay, China, which is close to
the fast-developing megacities such as Beijing and Tianjin, and dated using
excess Pb-210 and Cs-137. Using the constant rate of supply model (CRS), the
temporal variation of sedimentation rates over the last 100years in Bohai Bay was
determined, and its main factors influencing sedimentation rates were discussed.
The sedimentation rates before 1980 were relatively stable, ranging from 0.26+/
0.04g/(cm2.y) in 1920 to 0.39+/-0.08g/(cm2.y) in 1980. A gradual increase in
sedimentation rate was found from 0.39+/-0.08g/(cm2.y) in 1980 to 0.84+/
0.13g/(cm2.y) in 2010. Riverine input was the main factors influencing
sedimentation rates in Bohai Bay before 1980. After 1980, the accelerated
increase in sedimentation rate may be attributed to the large-scale reclamation
along the coastline. It is worth noting that eutrophication caused by an increase
in sewage discharge and overuse of chemical fertilizer, also may influence recent
acceleration in sedimentation rate.
PMID- 27494656
TI - Characterization of brominated flame retardants in construction and demolition
waste components: HBCD and PBDEs.
AB - The vast majority of construction material is inert and can be managed as
nonhazardous. However, structures may have either been built with some
environmentally unfriendly substances such as brominated flame retardants (BFRs),
or have absorbed harmful elements such as heavy metals. This study focuses on end
of-life construction materials, i.e. construction and demolition (C&D) waste
components. The aim was to characterize the concentration of extremely harmful
substances, primarily BFRs, including hexabromocyclododecane (HBCD) and
polybrominateddiphenyl ethers (PBDEs). Results revealed extremely high contents
of HBCD and PBDEs in typical C&D waste components, particularly polyurethane foam
materials. Policies should therefore be developed for the proper management of
C&D waste, with priority for POP-containing debris. The first priority is to
develop a classification system and procedures to separate out the harmful
materials for more extensive processing. Additionally, identification and
quantification of the environmental implications associated with dumping
dominated disposal of these wastes are required. Finally, more sustainable
materials should be selected for use in the construction industry.
PMID- 27494657
TI - Arbuscular mycorrhizal fungi-assisted phytoremediation of a lead-contaminated
site.
AB - Knowledge of the behavior of plant species associated with arbuscular mycorrhizal
fungi (AMF) and the ability of such plants to grow on metal-contaminated soils is
important to phytoremediation. Here, we evaluate the occurrence and diversity of
AMF and plant species as well as their interactions in soil contaminated with
lead (Pb) from the recycling of automotive batteries. The experimental area was
divided into three locations: a non-contaminated native area, a coarse rejects
deposition area, and an area receiving particulate material from the chimneys
during the Pb melting process. Thirty-nine AMF species from six families and 10
genera were identified. The Acaulospora and Glomus genera exhibited the highest
occurrences both in the bulk (10 and 6) and in the rhizosphere soils (9 and 6).
All of the herbaceous species presented mycorrhizal colonization. The highest Pb
concentrations (mgkg-1) in roots and shoots, respectively, were observed in
Vetiveria zizanoides (15,433 and 934), Pteris vitata (9343 and 865), Pteridim
aquilinun (1433 and 733), and Ricinus communis (1106 and 625). The diversity of
AMF seems to be related to the area heterogeneity; the structure communities of
AMF are correlated with the soil Pb concentration. We found that plant diversity
was significantly correlated with AMF diversity (r=0.645; P>0.05) in areas with
high Pb soil concentrations. A better understanding of AMF communities in the
presence of Pb stress may shed light on the interactions between fungi and metals
taking place in contaminated sites. Such knowledge can aid in developing soil
phytoremediation techniques such as phytostabilization.
PMID- 27494658
TI - Alpine vegetation phenology dynamic over 16years and its covariation with climate
in a semi-arid region of China.
AB - Vegetation phenology is a sensitive indicator of ecosystem response to climate
change, and plays an important role in the terrestrial biosphere. Improving our
understanding of alpine vegetation phenology dynamics and the correlation with
climate and grazing is crucial for high mountains in arid areas subject to
climatic warming. Using a time series of SPOT Normalized Difference Vegetation
Index (NDVI) data from 1998 to 2013, the start of the growing season (SOS), end
of the growing season (EOS), growing season length (GSL), and maximum NDVI
(MNDVI) were extracted using a threshold-based method for six vegetation groups
in the Heihe River headwaters. Spatial and temporal patterns of SOS, EOS, GSL,
MNDVI, and correlations with climatic factors and livestock production were
analyzed. The MNDVI increased significantly in 58% of the study region, whereas
SOS, EOS, and GSL changed significantly in <5% of the region. The MNDVI in five
vegetation groups increased significantly by a range from 0.045 to 0.075. No
significant correlation between SOS and EOS was observed in any vegetation group.
The SOS and GSL were highly correlated with temperature in May and April-May,
whereas MNDVI was correlated with temperature in August and July-August. The EOS
of different vegetation groups was correlated with different climatic variables.
Maximum and minimum temperature, accumulated temperature, and effective
accumulated temperature showed stronger correlations with phenological metrics
compared with those of mean temperature, and should receive greater attention in
phenology modeling in the future. Meat and milk production were significantly
correlated with the MNDVI of scrub, steppe, and meadow. Although the MNDVI
increased in recent years, ongoing monitoring for rangeland degradation is
recommended.
PMID- 27494659
TI - Reduced carbon sequestration potential of biochar in acidic soil.
AB - Biochar application in soil has been proposed as a promising method for carbon
sequestration. While factors affecting its carbon sequestration potential have
been widely investigated, the number of studies on the effect of soil pH is
limited. To investigate the carbon sequestration potential of biochar across a
series of soil pH levels, the total carbon emission, CO2 release from inorganic
carbon, and phospholipid fatty acids (PLFAs) of six soils with various pH levels
were compared after the addition of straw biochar produced at different pyrolysis
temperatures. The results show that the acidic soils released more CO2 (1.5-3.5
times higher than the control) after the application of biochar compared with
neutral and alkaline soils. The degradation of both native soil organic carbon
(SOC) and biochar were accelerated. More inorganic CO2 release in acidic soil
contributed to the increased degradation of biochar. Higher proportion of gram
positive bacteria in acidic soil (25%-36%) was responsible for the enhanced
biochar degradation and simultaneously co-metabolism of SOC. In addition, lower
substrate limitation for bacteria, indicated by higher C-O stretching after the
biochar application in the acidic soil, also caused more CO2 release. In addition
to the soil pH, other factors such as clay contents and experimental duration
also affected the phsico-chemical and biotic processes of SOC dynamics. Gram
negative/gram-positive bacteria ratio was found to be negatively related to
priming effects, and suggested to serve as an indicator for priming effect. In
general, the carbon sequestration potential of rice-straw biochar in soil reduced
along with the decrease of soil pH especially in a short-term. Given wide spread
of acidic soils in China, carbon sequestration potential of biochar may be
overestimated without taking into account the impact of soil pH.
PMID- 27494660
TI - A preliminary nationwide survey of the presence of emerging contaminants in
drinking and source waters in Brazil.
AB - This is the first nationwide survey of emerging contaminants in Brazilian waters.
One hundred drinking water samples were investigated in 22 Brazilian state
capitals. In addition, seven source water samples from two of the most populous
regions of the country were evaluated. Samples were collected from June to
September of 2011 and again during the same period in 2012. The study covered
emerging contaminants of different classes, including hormones, plasticizers,
herbicides, triclosan and caffeine. The analytical method for the determination
of the compounds was based on solid-phase extraction followed by analysis via
liquid chromatography electrospray triple-quadrupole mass spectrometry (LC
MS/MS). Caffeine, triclosan, atrazine, phenolphthalein and bisphenol A were found
in at least one of the samples collected in the two sampling campaigns. Caffeine
and atrazine were the most frequently detected substances in both drinking and
source water. Caffeine concentrations in drinking water ranged from 1.8ngL-1 to
values above 2.0MUgL-1 while source-water concentrations varied from 40ngL-1 to
about 19MUgL-1. For atrazine, concentrations were found in the range from 2.0 to
6.0ngL-1 in drinking water and at concentrations of up to 15ngL-1 in source
water. The widespread presence of caffeine in samples of treated water is an
indication of the presence of domestic sewage in the source water, considering
that caffeine is a compound of anthropogenic origin.
PMID- 27494661
TI - Detecting the impact of heavy metal contaminated sediment on benthic
macroinvertebrate communities in tropical streams.
AB - The effects of heavy metal pollution on benthic macroinvertebrate communities in
tropical streams draining ultramafic systems have not been explored, despite a
pressing need for ecological risk assessment to protect and manage aquatic
ecosystems in these areas. The objective of this study was to examine benthic
macroinvertebrate community composition in relation to metal concentrations in
stream sediments and other physico-chemical variables in the Manyame River
system, which drains part of the Great Dyke of Zimbabwe. Benthic
macroinvertebrate sampling and community composition analysis, sediment
collection, processing and metal analysis and assessment of other variables in
the water column were done once at 55 sampling sites: 12 urban, 30 communal (i.e.
sparsely populated rural areas, with livelihoods centred around subsistence
agriculture) and 11 Great Dyke sites. Canonical correspondence analysis and
partial canonical correspondence analysis (pCCA) were used to determine the
importance of sediment heavy metal concentrations in explaining benthic
macroinvertebrate community composition in comparison with other factors. Water
quality ranged from very poor for urban locations due to sewage pollution, to
good in communal locations. Significantly high concentrations of metals (ANOVA,
p<0.05) and high magnesium/calcium (Mg/Ca) ratio were recorded in sediments for
the Great Dyke site locations. The Mg/Ca ratio, Ca2+, Cr3+ and K+ were found to
be important metals structuring benthic macroinvertebrate communities in the
study streams, with metals explaining a larger percentage (58.0%) of the total
variation explained compared to other variables (35.9%). However, taxa richness,
diversity, evenness, percentage of Ephemeroptera, Plecoptera Trichoptera related
metrics were higher at some Great Dyke sites than at communal sites. Thus,
measures of taxa richness, diversity and %EPT may provide misleading information
when assessing heavy metals in moderately polluted environments as in this study.
Assessment of tropical streams draining ultramafic systems that are heavy metal
contaminated should also include benthic invertebrate community structure
analysis, as it is possible that common endpoints, such as %EPT, may not identify
impacts to aquatic communities.
PMID- 27494662
TI - The relation between outcome expectation, therapeutic alliance, and outcome among
depressed patients in group cognitive-behavioral therapy.
AB - OBJECTIVE: Although patients' expectation for improvement correlates with their
treatment outcome, there remains limited information regarding the mechanisms
through which outcome expectation influences outcome. Although several studies
have revealed alliance as a mediator of the expectancy-outcome relation, most
have focused on individual psychotherapy only. More research is needed examining
mediators, including alliance quality, of the outcome expectation-outcome
relation in group therapy. METHOD: This study focused on such associative chains
among 91 depressed outpatients who completed 10 weeks of group cognitive
behavioral therapy. We conducted simple and multiple mediation analyses,
accounting for the nested data structure. RESULTS: As predicted, we found: (i)
The relations between baseline outcome expectation and both posttreatment anxiety
and depression were mediated by alliance quality; (ii) the early therapy outcome
expectation-posttreatment anxiety relation was mediated by mid-treatment
alliance; (iii) the relation between early alliance and posttreatment
interpersonal problems was mediated by during-therapy outcome expectation; and
(iv) the relation between baseline outcome expectation and posttreatment
interpersonal problems was mediated by two variables acting in turn, early
alliance and during-therapy outcome expectation. All other tested models were not
significant. CONCLUSIONS: Results suggest that bidirectional relations between
outcome expectation and alliance, with both directions influencing outcome.
Clinical and empirical implications are discussed.
PMID- 27494663
TI - Discrimination and mental health among Latinos: variation by place of origin.
AB - The US Latino population experiences high rates of discrimination, which may
contribute to psychiatric disorders. Yet, little is known about the distinctions
in this relationship for Latino subgroups. Using data from the National Latino
and Asian American study, we examined the association between discrimination and
mental health for 2503 Latinos. Logistic regression analyses were used to examine
variation in the relationship by place of origin (Cuba, Puerto Rico, Mexico, or
Other). Results suggest that perceived discrimination increased the probability
of having a psychiatric disorder. The effect of discrimination on having a
psychiatric disorder was greater for Mexicans than Puerto Ricans. The findings of
this study suggest that variation exists in the relationship between
discrimination and mental health by origin. Implications for practice include
increasing awareness of place of origin, in addition to discrimination, as a risk
factor for mental illness. Future research should examine this relationship
longitudinally and consider immigration status.
PMID- 27494665
TI - "If You See Something, Say Something".
PMID- 27494664
TI - Cytotoxic Tirucallane and Apotirucallane Triterpenoids from the Stems of Picrasma
quassioides.
AB - Phytochemical investigation on the stems of Picrasma quassioides led to the
isolation of a novel compound, picraquassin A (1), with an unprecedented 21,24
cycloapotirucallane skeleton, and four new apotirucallane-type triterpenoids (2
5), together with 15 new tirucallane-type triterpenoids (6-20) and 10 known
tirucallane-type triterpenoids (21-30). To our knowledge, this is the first
report demonstrating the presence of apotirucallane-type triterpenoids in the
genus Picrasma. The structures of the new compounds were determined based on
spectroscopic data interpretation. Cytotoxicities of the isolated compounds were
evaluated using three human cancer cell lines, MKN-28, A-549, and MCF-7. Compound
2 exhibited the most potent activity against MKN-28 cells with an IC50 value of
2.5 MUM. Flow cytometry and Western blot analysis revealed that 2 induces the
apoptosis of MKN-28 cells via activating caspase-3/-9, while increasing Bax and
Bad and decreasing Bcl-2 expression levels.
PMID- 27494666
TI - ADARs Edit MicroRNAs to Promote Leukemic Stem Cell Activity.
AB - Leukemic stem cells (LSCs) drive progression of chronic myeloid leukemia (CML)
and tyrosine kinase inhibitor resistance through poorly understood mechanisms.
Now in Cell Stem Cell, Zipeto et al. (2016) show targeting the RNA editing enzyme
ADAR1 restores expression of let-7 and efficiently kills LSCs, providing an
innovative therapeutic target in CML.
PMID- 27494667
TI - Stressed-Out HSCs Turn Up p38alpha and Purine to Proliferate.
AB - Changes in cellular metabolism drive hematopoietic stem cell (HSC) behavior
during homeostasis, although whether they control HSC behavior during stress
conditions is unclear. In this issue of Cell Stem Cell, Karigane et al. (2016)
identify a p38alpha-dependent pathway that alters purine metabolism in HSCs
during stress hematopoiesis, promoting hematopoietic recovery.
PMID- 27494668
TI - Neural Differentiation in the Third Dimension: Generating a Human Midbrain.
AB - In recent years, technological improvements in three-dimensional (3D) culture
systems have enabled the generation of organoids or spheroids representing a
variety of tissues, including the brain. In this issue of Cell Stem Cell, Jo et
al. (2016) describe a 3D culture model of the human midbrain containing
dopaminergic neurons and neuromelanin.
PMID- 27494669
TI - Mesoderm, Cooked Up Fast and Served to Order.
AB - New sequencing technologies have made it possible to interrogate with
unprecedented depth the intrinsic changes experienced by cells as they transit
the arena of development. Recently in Cell, Loh, Chen, and colleagues
investigated early lineage-restricted human mesoderm cell types and their
precursors going back to pluripotency (Loh et al., 2016).
PMID- 27494670
TI - Hematopoietic Lineage Diversification, Simplified.
AB - Hematopoiesis is a complex process that requires a high degree of transcriptional
diversification during lineage commitment and differentiation. de Graaf et al.
(2016) have now generated a comprehensive gene expression dataset that allows
cell-type-specific genes as well as associated transcription factor expression
patterns to be readily identified.
PMID- 27494671
TI - Deteriorating Infrastructure in the Aged Muscle Stem Cell Niche.
AB - Following an injury, the extracellular matrix (ECM) undergoes dramatic remodeling
to facilitate tissue repair. In a new study, Lukjanenko and colleagues show how
an age-associated change in this process affects the regenerative ability of
muscle stem cells (MuSCs).
PMID- 27494672
TI - Current Public Support for Human-Animal Chimera Research in Japan Is Limited,
Despite High Levels of Scientific Approval.
PMID- 27494673
TI - Global Distribution of Businesses Marketing Stem Cell-Based Interventions.
AB - A structured search reveals that online marketing of stem-cell-based
interventions is skewed toward developed economies including the United States,
Ireland, Australia, and Germany. Websites made broad, imprecise therapeutic
claims and frequently failed to detail procedures. Widespread marketing poses
challenges to regulators, bioethicists, and those seeking realistic hope from
therapies.
PMID- 27494675
TI - Environmental factors in the etiology of isolated and nonisolated esophageal
atresia in a Chinese population: A case-control study.
AB - BACKGROUND: Esophageal atresia (EA) is a common birth defect that occurs with
tracheoesophageal fistula (TEF), although etiological studies on EA/TEF have
produced inconsistent results. METHODS: The aim of this study was to examine the
association between environmental factors during pregnancy and the risk of EA/TEF
in a Chinese population. Cases of isolated EA and nonisolated EA and unaffected
controls were identified between July 2005 and November 2015, and face-to-face
questionnaires concerning exposure to environmental factors were administered to
the birth mothers of 130 cases and 400 controls. The adjusted odds ratio (OR) and
95% confidence interval (CI) were calculated to assess the association between
environmental factors and the risk of EA/TEF. RESULTS: The results of this case
control study suggest that lower maternal education (p < 0.0001), maternal binge
drinking (OR = 2.63; 95% CI, 1.05-6.6) and pickled food consumption (OR = 2.04;
95% CI, 1.31-3.71) during pregnancy increase the risk of EA in offspring, while
maternal folic acid supplementation (OR = 0.45; 95% CI, 0.29-0.71) is
significantly associated with a decreased risk of EA. CONCLUSION: These results
suggest a role for environmental exposures in the etiology of EA/TEF; however,
further studies are needed to replicate the observed associations. Birth Defects
Research (Part A) 106:840-846, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27494674
TI - Contributions of Mammalian Chimeras to Pluripotent Stem Cell Research.
AB - Chimeras are widely acknowledged as the gold standard for assessing stem cell
pluripotency, based on their capacity to test donor cell lineage potential in the
context of an organized, normally developing tissue. Experimental chimeras
provide key insights into mammalian developmental mechanisms and offer a resource
for interrogating the fate potential of various pluripotent stem cell states. We
highlight the applications and current limitations presented by intra- and inter
species chimeras and consider their future contribution to the stem cell field.
Despite the technical and ethical demands of experimental chimeras, including
human-interspecies chimeras, they are a provocative resource for achieving
regenerative medicine goals.
PMID- 27494676
TI - Risk Factors for Glaucoma in a Cohort of Patients with Fuchs Heterochromic
Iridocyclitis.
AB - PURPOSE: To describe the incidence and risk factors for ocular hypertension
and/or glaucoma in patients with Fuchs heterochromic iridocyclitis (FHC).
METHODS: Retrospective analysis of 88 patients with FHC. Kaplan-Meier curves
estimated the time to develop cataract and ocular hypertension/glaucoma. Possible
prognostic factors were investigated in univariate Kaplan-Meier analyses using
the Mantel-Cox logrank test. RESULTS: At presentation with FHC, 52% of patients
had a cataract and 26% of patients had ocular hypertension/glaucoma. The
estimated percentage of patients with a cataract or ocular hypertension/glaucoma
by 4 years after presentation was 71% (CI: 58-81%) and 39% (CI: 28-51%),
respectively. Patients aged >=50 years had significantly greater risk of
developing glaucoma (p = 0.0065). After adjusting for age-group, having a
cataract at presentation was associated with increased risk of glaucoma (p =
0.032). CONCLUSIONS: Risk factors for development of ocular hypertension/glaucoma
were increasing patient age and having a cataract at presentation with FHC.
PMID- 27494677
TI - Finding Peace Beyond the Pain: Sunder's Journey in the Hospice.
AB - Dame Cicely Saunders revolutionized the concept of pain by coining the term
"total pain", the sum of the physical, psychological, social, spiritual,
emotional components that make up the total pain experience. Optimal pain relief
may not be possible until all elements of the pain and suffering are addressed.
This narrative describes the journey of Sunder in the hospice. A caring husband,
and a doting father, he came to the hospice by force, in immense pain and
suffering. He stayed on by choice and found the peace he was looking for beyond
his pain and sufferings, ably supported by the dedicated hospice team. He was
able to live the last few months of his life as comfortably as was possible, and
left this world in peace, with dignity. The narrative reiterates the belief that
hospice, with its philosophy of active "total care" is an ideal place for
addressing the concept of "total pain."
PMID- 27494678
TI - Adverse effects of bisphenol A (BPA) on the dopamine system in two distinct cell
models and corpus striatum of the Sprague-Dawley rat.
AB - The aim of this study was to examine the effects of bisphenol A (BPA) on the
brain dopamine (DA) system utilizing both in vitro models (GH3 cells, a rat
pituitary cell line, and SH-SY5Y cells, a human neuroblastoma cell line) and an
animal model such as Sprague-Dawley (SD) rats. First, cellular DA uptake was
measured 2 or 8 h following BPA exposure (0.1-400 MUM) in SH-SY5Y cells, where a
significant increase in DA uptake was noted. BPA exerted no marked effect on
dopamine active transporter levels in GH3 cells exposed for 8 or 24 h. However,
SH-SY5Y cells displayed an increase in dopamine transporter (DAT) levels
following 24 h of exposure to BPA. In contrast to DAT levels, BPA exposure
produced no marked effect on DA D1 receptor levels in SH-SY5Y cells, yet a
significant decrease in GH3 cells following both 8- and 24-h exposure periods was
noted, suggesting that BPA exerts differential effects dependent upon cell type.
BPA produced no significant effects on prolactin levels at 2 h, but a marked fall
occurred at 24 h of exposure in GH3 cells. Finally, to examine the influence of
dietary developmental exposure to BPA on brain DA levels in F1 offspring, SD rats
were exposed to BPA (0.5-20 mg/kg) through maternal transfer and/or diet and
striatal DA levels were measured on postnatal day (PND) 60 using high-performance
liquid chromatography (HPLC). Data demonstrated that chronic exposure to BPA did
not significantly alter striatal DA levels in the SD rat.
PMID- 27494679
TI - [Femtosecond Laser-Assisted Cataract Surgery: Current Status and Outlook].
PMID- 27494680
TI - [Ocular Lymphomas].
PMID- 27494681
TI - [Management of Periocular Soft Tissue Injuries].
PMID- 27494682
TI - [LASIK and Femto-LASIK].
PMID- 27494683
TI - High-fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by
betaine treatment in rats.
AB - Steatosis, the first lesion in non-alcoholic fatty liver disease (NAFLD), may
progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Steatosis
predisposes the liver to oxidative stress, inflammation, and cytokines. Betaine
(BET) has antioxidant, antiinflammatory and hepatoprotective effects. However,
the effects of BET on liver fibrosis development are unknown. Rats were treated
with high-fat diet (60% of total calories from fat) for 14weeks. Carbon
tetrachloride (0.2mL/kg; two times per week; i.p.) was administered to rats in
the last 6weeks with/without commercial food containing BET (2%; w/w). Serum
liver function tests and tumor necrosis factor-alpha, insulin resistance, hepatic
triglyceride (TG) and hydroxyproline (HYP) levels and oxidative stress parameters
were determined along with histopathologic observations. Alpha-smooth muscle
actin (alpha-SMA), transforming growth factor-beta1 (TGF-beta1) and type I
collagen (COL1A1) protein expressions and mRNA expressions of matrix
metalloproteinase-2 (MMP-2) and its inhibitors (TIMP-1 and TIMP-2) were
evaluated. BET decreased TG and HYP levels, prooxidant status and fibrotic
changes in the liver. alpha-SMA, COL1A1 and TGF-beta1 protein expressions, MMP-2,
TIMP-1, and TIMP-2 mRNA expressions diminished due to BET treatment. BET has an
antifibrotic effect and this effect may be related to its antioxidant and
antiinflammatory actions together with suppression on HSC activation.
PMID- 27494684
TI - Asiatic acid inhibits pulmonary inflammation induced by cigarette smoke.
AB - Asiatic acid (AA) is one of the major components of Titrated extract of Centella
asiatica (TECA), which has been reported to possess antioxidant and anti
inflammatory activities. The purpose of this study was to investigate the
protective effect of AA on pulmonary inflammation induced by cigarette smoke
(CS). AA significantly attenuated the infiltration of inflammatory cells in
bronchoalveolar lavage fluid (BALF) of CS exposure mice. AA also decreased ROS
production and NE activity, and inhibited the release of proinflammatory
cytokines in BALF. AA reduced the recruitment of inflammatory cells and MCP-1
expression in lung tissue of CS exposure mice. AA also attenuated mucus
overproduction, and decreased the activation of MAPKs and NF-kB in lung tissue.
Furthermore, AA increased HO-1 expression and inhibited the reduced expression of
SOD3 in lung tissue. These findings indicate that AA effectively inhibits
pulmonary inflammatory response, which is an important process in the development
of chronic obstructive pulmonary disease (COPD) via suppression of inflammatory
mediators and induction of HO-1. Therefore, we suggest that AA has the potential
to treat inflammatory disease such as COPD.
PMID- 27494685
TI - Enhanced effect of kappa-carrageenan on TNBS-induced inflammation in mice.
AB - BACKGROUND: As a sulfated polysaccharide, carrageenan has been widely used as
common food additive. METHODS: In the present study, we investigated the effects
of kappa-carrageenan on TNBS-induced gut inflammation in mice. BALB/c mice were
pretreated with kappa-carrageenan for 14days prior to the administration of TNBS.
RESULTS: Our results showed that kappa-carrageenan pretreatment aggravated the
loss of body weight and further increased the mortality rate. Histological and
morphological analyses revealed that the TNBS-induced colonic inflammation was
deteriorated by the kappa-carrageenan administration. The ratio of
CD4(+)CD25(+)CD127dim/CD4(+) of the kappa-carrageenan+TNBS groups was
significantly lower than that of the TNBS group. The expression of IL-2, TNF
alpha and IL-6 was significantly increased, whereas the expression of IL-10 was
significantly decreased in the kappa-carrageenan+TNBS groups. In addition, kappa
carrageenan, together with TNBS, decreased the enzyme activity of SOD and GSH-px
and up-regulated the expression of TLR4, NF-kappaB, p-ERK, p-JNK, p-Jun., IL-8
and MDA in the colonic mucosa. CONCLUSIONS: kappa-Carrageenan aggravated the TNBS
induced intestinal inflammation, and such an effect could be associated with the
oxidative stress and activation of TLR4-NF-kappaB and MAPK/ERK1/2 pathway.
PMID- 27494686
TI - Lipoxin A4 protects against lipopolysaccharide-induced sepsis by promoting innate
response activator B cells generation.
AB - Sepsis is a serious disease that leads to severe inflammation, dysregulation of
immune system, multi-organ failure and death. Innate response activator (IRA) B
cells, which produce granulocyte-macrophage colony-stimulating factor (GM-CSF),
protect against microbial sepsis. Lipid mediator lipoxin A4 (LXA4) exerts anti
inflammatory and immunoregulatory effects, and it has been reported that LXA4
receptor ALX/FPR2 is expressed on B cells. Here, we investigated the potential
role of LXA4 on IRA B cells in lipopolysaccharide (LPS)-induced sepsis. We found
that LXA4 significantly promoted the expansion of splenic IRA B cells and
increased GM-CSF expression in splenic B cells with LPS stimulation. After
splenectomy, LXA4 treatment did not change the serum or peritoneal IL-1beta, IL-6
and TNF-alpha levels in LPS-induced sepsis. LXA4 accelerated the migration of
peritoneal B cells to spleen for their differentiation into IRA B cells, whereas
this effect was independent of peritoneal macrophage. Furthermore, LXA4 enhanced
the phosphorylation level of signal transducer and activator of transcription 5
(STAT5) in splenic B cells. These results suggest that LXA4 protects against LPS
induced sepsis by promoting the generation and migration of splenic IRA B cells,
and the underlying molecular mechanism may be related to STAT5 activation. It
might provide new insights and therapeutic approaches for treating sepsis.
PMID- 27494687
TI - Betahistine attenuates murine collagen-induced arthritis by suppressing both
inflammatory and Th17 cell responses.
AB - The objective of this study was to evaluate the potential therapeutic effects of
betahistine dihydrochloride (betahistine) in a collagen-induced arthritis (CIA)
mouse model. CIA was induced in DBA/1 male mice by primary immunization with
100MUl of emulsion containing 2mg/ml chicken type II collagen (CII) mixed with
complete Freund's adjuvant (CFA) in an 1:1 ratio, and booster immunization with
100MUl of emulsion containing 2mg/ml CII mixed with incomplete Freund's adjuvant
(IFA) in an 1:1 ratio. Immunization was performed subcutaneously at the base of
the tail. After being boosted on day 21, betahistine (1 and 5mg/kg) was orally
administered daily for 2weeks. The severity of CIA was determined by arthritic
scores and assessment of histopathological joint destruction. Expression of
cytokines in the paw and anti-CII antibodies in the serum was evaluated by ELISA.
The proliferative response against CII in the lymph node cells was measured by
(3)H-thymidine incorporation assay. The frequencies of different CII specific
CD4(+) T cell subsets in the lymph node were determined by flow-cytometric
analysis. Betahistine treatment attenuated the severity of arthritis and reduced
the levels of pro-inflammatory cytokines, including TNF-alpha, IL-6, IL-23 and IL
17A, in the paw tissues of CIA mice. Lymph node cells from betahistine-treated
mice showed a decrease in proliferation, as well as a lower frequency of Th17
cells. In vitro, betahistine suppressed CD4(+) T cell differentiation into Th17
cells. These results indicate that betahistine is effective in suppressing both
inflammatory and Th17 responses in mouse CIA and that it may have therapeutic
value as an adjunct treatment for rheumatoid arthritis.
PMID- 27494688
TI - Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced
diabetic cardiomyopathy.
AB - T cell infiltration has been associated with increased coronary heart disease
risk in patients with diabetes mellitus. Effect of modulation of T cell
trafficking on diabetes-induced cardiac fibrosis has yet to be determined.
Therefore, our aim was to investigate the circulatory T cell depletion-mediated
cardioprotection in streptozotocin-induced diabetic cardiomyopathy. Fingolimod
(FTY720), an immunomodulatory drug, was tested in wild-type (WT) C57BL/6 and
recombination activating gene 1 (Rag1) knockout (KO) mice without mature
lymphocytes in streptozotocin-induced type 1 diabetic model. FTY720
(0.3mg/kg/day) was administered intraperitoneally daily for the first 4weeks with
interim 3weeks then resumed for another 4weeks in 11weeks study period. T
lymphocyte counts, cardiac histology, function, and fibrosis were examined in
diabetic both WT and KO mice. FTY720 reduced both CD4(+) and CD8(+) T cells in
diabetic WT mice. FTY720-treated diabetic WT mouse myocardium showed reduction in
CD3 T cell infiltration and decreased expression of S1P1 and TGF-beta1 in cardiac
tissue. Fibrosis was reduced after FTY720 treatment in diabetic WT mice. Rag1 KO
mice exhibited no CD4(+) and CD8(+) T cells in the blood and CD3 T cells in the
heart. Diabetic Rag1 KO mouse hearts appeared no fibrosis and exhibited preserved
myocardial contractility. FTY720-induced antifibrosis was abolished in diabetic
Rag1 KO mice. These findings demonstrate that chronic administration with FTY720
induces lymphopenia and protects diabetic hearts in WT mice whereas FTY720
increases cardiac fibrosis and myocardial dysfunction in diabetic Rag1 KO mice
without mature lymphocytes.
PMID- 27494689
TI - Effects of rule changes on physical demands and shot characteristics of elite
standard men's squash and implications for training.
AB - The physical demands and rally characteristics of elite-standard men's squash
have not been well documented since recent rule changes (scoring and tin height).
This information is needed to design optimal training drills for physical
conditioning provided here based on an analysis of movement and shot information.
Matches at the 2010 (n = 14) and 2011 (n = 27) Rowe British Grand Prix were
analysed. Rallies were split into four ball-in-play duration categories using the
25th (short), 75th (medium), 95th percentiles (long) and maximum values. Cohen's
d and chi-squared tests of independence evaluated effects of rally and rule
changes on patterns of play. The proportion of long, middle and short shots was
related to the duration of the rally with more shots played in the middle and
front of the court in short rallies (phi = 0.12). The frequencies of shots played
from different areas of the court have not changed after the adoption of new
rules but there is less time available to return shots that reflect the attacking
nature of match play for elite-standard men players. Aspiring and current elite
standard players need to condition themselves to improve their ability to cope
with these demands using the ghosting patterns presented that mimic demands of
modern match play.
PMID- 27494690
TI - Ab initio study of magnetoelectric coupling in La0.66Sr0.33MnO3 / PbZr0.2Ti0.8O3
multiferroic heterostructures.
AB - Multiferroic heterostructures composed of thin layers of ferromagnetic and
ferroelectric perovskites have attracted considerable attention in recent years.
We apply ab initio computational methods based on density functional theory to
study the magnetoelectric coupling at the (0 0 1) interface between [Formula: see
text] (LSMO) and [Formula: see text] (PZT). Our study demonstrates that the
ferroelectric polarization of PZT has a strong influence on the distribution of
magnetization in LSMO. The presence of polarized PZT changes the balance between
the ferromagnetic and antiferromagnetic states of LSMO. The observed interfacial
magnetoelectric effect can be explained by the variation of the charge density
across the LSMO/PZT interface and by the change of the magnetic order in the LSMO
layer adjacent to PZT.
PMID- 27494691
TI - The Structure of the Carbene Stabilized Si2H2 May Be Equally Well Described with
Coordinate Bonds as with Classical Double Bonds.
AB - The cyclic alkyl(amino) carbene stabilized Si2H2 has been isolated in the
molecular form of composition (Me-cAAC:)2Si2H2 (1) and (Cy-cAAC:)2Si2H2 (2) at
room temperature. Compounds 1 and 2 were synthesized from the reduction of HSiCl3
using 3 equiv of KC8 in the presence of 1 equiv of Me-cAAC: and Cy-cAAC:,
respectively. These are the first molecular examples of Si2H2 characterized by
single crystal X-ray structural analysis. Moreover, electrospray ionization mass
spectrometry and (1)H as well as (29)Si NMR data are reported. Furthermore, the
structure of compound 1 has been investigated by theoretical methods. The
theoretical analysis of 1 explains equally well its structure with coordinate
bonds as with classical double bonds of a 2,3-disila-1,3-butadiene.
PMID- 27494692
TI - Real world evidence of use of anti-VEGF therapy in Denmark.
AB - OBJECTIVE: This study evaluates real-world evidence regarding the frequency of
anti-vascular-endothelial-growth-factor (VEGF) injections during the first year
of therapy of treatment-naive patients with neovascular age-related macular
degeneration (nAMD), diabetic macular edema (DME) and retinal vein occlusion
(RVO) from the Danish National Patient Registry. There was a switch in anti-VEGF
treatment for naive nAMD patients during the study period, following the
introduction of aflibercept, which was expected to reduce the injection frequency
relative to ranibizumab due to a perception of prolonged treatment duration of
aflibercept. METHODS: All treatment-naive nAMD, DME or RVO patients who received
an intravitreal injection in Denmark from 1 January 2012 to 31 July 2015 were
eligible for inclusion. Patients were required to have been treated for at least
one year and, for nAMD, to have received at least three injections during the
first four months of treatment. Patients were allocated to half-year groupings
(2012/1 to 2014/1) based on registration of their first intravitreal injection.
Injection frequency during the first year of treatment was calculated for each
group and t-tests investigated whether injection frequencies changed over time.
RESULTS: In treatment naive nAMD patients (n = 500), the mean (SD) number of anti
VEGF injections increased significantly from 6.04 (1.71) in 2012/1 to 6.73 (1.62)
in 2014/1 (p = .001; 2012/1 and 2012/2 vs. 2014/1) across all treatments. A
similar trend was found for DME patients (n = 76) from 2012/1 to 2014/1 and RVO
patients (n = 82) from 2012/2 to 2014/1, with mean injection frequencies
increasing significantly from 5.14 (2.29) to 5.93 (1.98) (p = .007), and from
4.83 (1.21) to 6.08 (1.55) (p = .024), respectively. Post hoc sensitivity
analysis also found a significant increase in injection frequency in nAMD
patients who did not receive a loading phase (4.55 in 2012/1 and 5.05 in 2014/1;
p = .006; n = 616). CONCLUSIONS: In contrast to the decrease in injection
frequency predicted with a switch to aflibercept treatment for nAMD, our study
showed that injection frequencies increased significantly from 2012 to 2014 in
patients initiating therapy across the three diseases.
PMID- 27494693
TI - Effects of apelin on reproductive functions: relationship with feeding behavior
and energy metabolism.
AB - Apelin is an adipose tissue derived peptidergic hormone. In this study, 40 male
Sprague-Dawley rats were used (four groups; n = 10). Apelin-13 at three different
dosages (1, 5 and 50 MUg/kg) was given intraperitoneally while the control group
received vehicle the same route for a period of 14 days. In results, apelin-13
caused significant decreases in serum testosterone, luteinizing hormone and
follicle-stimulating hormone levels (p < 0.05). Administration of apelin-13
significantly increased body weights, food intake, serum low-density lipoprotein
and total cholesterol levels (p < 0.05), but caused significant decreases in high
density lipoprotein levels (p < 0.05). Serum glucose and triglyceride levels were
not significantly altered by apelin-13 administration. Significant decreases in
both uncoupling protein (UCP)-1 levels in the white and brown adipose tissues and
UCP-3 levels in the biceps muscle (p < 0.05) were noted. The findings of the
study suggest that apelin-13 may not only lead to obesity by increasing body
weight but also cause infertility by suppressing reproductive hormones.
PMID- 27494694
TI - Electron Shuttles Enhance Anaerobic Ammonium Oxidation Coupled to Iron(III)
Reduction.
AB - Anaerobic ammonium oxidation coupled to iron(III) reduction, termed Feammox, is a
newly discovered nitrogen cycling process. However, little is known about the
roles of electron shuttles in the Feammox reactions. In this study, two forms of
Fe(III) (oxyhydr)oxide ferrihydrite (ex situ ferrihydrite and in situ
ferrihydrite) were used in dissimilatory Fe(III) reduction (DIR) enrichments from
paddy soil. Evidence for Feammox in DIR enrichments was demonstrated using the
(15)N-isotope tracing technique. The extent and rate of both the (30)N2-(29)N2
and Fe(II) formation were enhanced when amended with electron shuttles (either
9,10-anthraquinone-2,6-disulfonate (AQDS) or biochar) and further simulated when
these two shuttling compounds were combined. Although the Feammox-associated
Fe(III) reduction accounted for only a minor proportion of total Fe(II) formation
compared to DIR, it was estimated that the potentially Feammox-mediated N loss
(0.13-0.48 mg N L(-1) day(-1)) was increased by 17-340% in the enrichments by the
addition of electron shuttles. The addition of electron shuttles led to an
increase in the abundance of unclassified Pelobacteraceae, Desulfovibrio, and
denitrifiers but a decrease in Geobacter. Overall, we demonstrated a stimulatory
effect of electron shuttles on Feammox that led to higher N loss, suggesting that
electron shuttles might play a crucial role in Feammox-mediated N loss from
soils.
PMID- 27494695
TI - Effects of organic matter addition on methylmercury formation in capped and
uncapped marine sediments.
AB - In situ subaqueous capping (ISC) of contaminated marine sediments is frequently
proposed as a feasible and effective mitigation option. However, though effective
in isolating mercury species migration into overlying water, capping can also
alter the location and extent of biogeochemical zones and potentially enhance
methylmercury (MeHg) formation in Hg-contaminated marine sediments. We carried
out a boxcosm study to investigate whether the addition of organic carbon (OC) to
Hg-contaminated marine sediments beneath an in situ cap would initiate and/or
enhance MeHg formation of the inorganic Hg present. The study was motivated by
ongoing efforts to remediate ca. 30,000 m(2) of Hg-contaminated seabed sediments
from a Hg spill from the U864 WWII submarine wreck. By the time of sinking, the
submarine is assumed to have been holding a cargo of ca. 65 tons of liquid Hg.
Natural organic matter and petroleum hydrocarbons from fuels and lubricants in
the wreck are potential sources of organic carbon that could potentially fuel
MeHg formation beneath a future cap. The results of our study clearly
demonstrated that introduction of algae OC to Hg-contaminated sediments,
triggered high rates of MeHg production as long a there was sufficient OC. Thus,
MeHg production was limited by the amount of organic carbon available. The study
results also confirmed that, within the six-month duration of the study and in
the absence of bioturbating fauna, a 3-cm sediment clay cap could effectively
reduce fluxes of Hg species to the overlying water and isolate the Hg
contaminated sediments from direct surficial deposition of organic matter that
could potentially fuel methylation.
PMID- 27494696
TI - Assessment of intermittently loaded woodchip and sand filters to treat dairy
soiled water.
AB - Land application of dairy soiled water (DSW) is expensive relative to its
nutrient replacement value. The use of aerobic filters is an effective
alternative method of treatment and potentially allows the final effluent to be
reused on the farm. Knowledge gaps exist concerning the optimal design and
operation of filters for the treatment of DSW. To address this, 18 laboratory
scale filters, with depths of either 0.6 m or 1 m, were intermittently loaded
with DSW over periods of up to 220 days to evaluate the impacts of depth (0.6 m
versus 1 m), organic loading rates (OLRs) (50 versus 155 g COD m(-2) d(-1)), and
media type (woodchip versus sand) on organic, nutrient and suspended solids (SS)
removals. The study found that media depth was important in contaminant removal
in woodchip filters. Reductions of 78% chemical oxygen demand (COD), 95% SS, 85%
total nitrogen (TN), 82% ammonium-nitrogen (NH4N), 50% total phosphorus (TP), and
54% dissolved reactive phosphorus (DRP) were measured in 1 m deep woodchip
filters, which was greater than the reductions in 0.6 m deep woodchip filters.
Woodchip filters also performed optimally when loaded at a high OLR (155 g COD m(
2) d(-1)), although the removal mechanism was primarily physical (i.e. straining)
as opposed to biological. When operated at the same OLR and when of the same
depth, the sand filters had better COD removals (96%) than woodchip (74%), but
there was no significant difference between them in the removal of SS and NH4N.
However, the likelihood of clogging makes sand filters less desirable than
woodchip filters. Using the optimal designs of both configurations, the filter
area required per cow for a woodchip filter is more than four times less than for
a sand filter. Therefore, this study found that woodchip filters are more
economically and environmentally effective in the treatment of DSW than sand
filters, and optimal performance may be achieved using woodchip filters with a
depth of at least 1 m, operated at an OLR of 155 g COD m(-2) d(-1).
PMID- 27494697
TI - Transformation of graphene oxide by chlorination and chloramination: Implications
for environmental transport and fate.
AB - The rapidly increasing and widespread use of graphene oxide (GO) calls for
immediate attention on the environmental fate of this material. To date, very
little is known about the environmental transformation of GO. This study explored
the changes of physicochemical properties of GO from chlorination and
chloramination, which simulated the reactions occurring in water and wastewater
treatment systems. Significant changes of GO surface O-functionalities occurred
and scrolling of graphene sheets (those of very large sizes) were observed upon
the treatments. Chloroform, a byproduct from chlorination was also detected,
indicating the ring-opening on the edge of GO nanosheets. The changes of GO
surface O-functionalities were attributable to the oxidation of quinone groups of
GO by chlorine or chloramine. The scrolling of large-sized GO sheets may be
attributable to the destruction of benzene rings at the edge of the GO. The
results of membrane filtration experiments and column transport experiments
indicated that chlorination and chloramination enhanced the mobility and
transport of GO, likely by increasing the colloidal stability and inhibiting the
agglomeration of GO nanosheets. The findings of this study further underline the
significant implications of GO transformation on the fate and transport of this
new nanomaterial.
PMID- 27494698
TI - Identification of transformation products during advanced oxidation of
diatrizoate: Effect of water matrix and oxidation process.
AB - Removal of micropollutants from reverse osmosis (RO) brines of wastewater
desalination by oxidation processes is influenced by the scavenging capacity of
brines components, resulting in the accumulation of transformation products (TPs)
rather than complete mineralization. In this work the iodinated contrast media
diatrizoate (DTZ) was used as model compound due to its relative resistance to
oxidation. Identification of TPs was performed in ultrapure water (UPW) and RO
brines applying nonthermal plasma (NTP) and UVA-TiO2 as oxidation techniques. The
influence of main RO brines components in the formation and accumulation of TPs,
such as chloride, bicarbonate alkalinity and humic acid, was also studied during
UVA-TiO2. DTZ oxidation pattern in UPW resulted similar in both UVA-TiO2 and NTP
achieving 66 and 61% transformation, respectively. However, DTZ transformation in
RO brines was markedly lower in UVA-TiO2 (9%) than in NTP (27%). These
differences can be attributed to the synergic effect of RO brines components
during NTP. Moreover, reactive species other than hydroxyl radical contributed to
DTZ transformation, i.e., direct photolysis in UVA-TiO2 and direct photolysis +
O3 in NTP accounted for 16 and 23%, respectively. DTZ transformation led to
iodide formation in both oxidation techniques but it further oxidized to iodate
by ozone in NTP. In total 14 transformation products were identified in UPW of
which 3 were present only in UVA-TiO2 and 2 were present exclusively in NTP; 5 of
the 14 TPs were absent in RO brines. Five of them were new and were denoted as TP
474A/B, TP-522, TP-586, TP-602, TP-628. TP-522 (mono-chlorinated) was elucidated
only in presence of high chloride titer-synthetic water matrix in NTP, most
probably formed by active chlorine species generated in situ. TPs accumulation in
RO brines was markedly different in comparison to UPW. This denotes the influence
of RO brines components in the formation of reactive species that could further
attack DTZ/TPs and/or scavenging performed by these brine components that could
limit further TPs degradation. Five plausible degradation pathways are proposed
for DTZ transformation in UPW.
PMID- 27494701
TI - Synthesis of Isoindolinones by Pd-Catalyzed Coupling between N-Methoxybenzamide
and Styrene Derivatives.
AB - An atom-economical protocol for a tandem process involving Fujiwara-Moritani-aza
Wacker reactions has been developed for the Pd-catalyzed coupling between N
methoxy benzamide and styrene derivatives. The generality of the methodology was
demonstrated by the synthesis of a library of 25 3-benzylidene isoindolinones in
moderate to good yields. A further 40 3-benzyl derivatives were obtained by
telescoping the process with a catalytic hydrogenation reaction.
PMID- 27494700
TI - Modeling and Simulation of Mucus Flow in Human Bronchial Epithelial Cell Cultures
- Part I: Idealized Axisymmetric Swirling Flow.
AB - A multi-mode nonlinear constitutive model for mucus is constructed directly from
micro- and macro-rheology experimental data on cell culture mucus, and a
numerical algorithm is developed for the culture geometry and idealized cilia
driving conditions. This study investigates the roles that mucus rheology, wall
effects, and HBE culture geometry play in the development of flow profiles and
the shape of the air-mucus interface. Simulations show that viscoelasticity
captures normal stress generation in shear leading to a peak in the air-mucus
interface at the middle of the culture and a depression at the walls. Linear and
nonlinear viscoelastic regimes can be observed in cultures by varying the
hurricane radius and mean rotational velocity. The advection-diffusion of a drug
concentration dropped at the surface of the mucus flow is simulated as a function
of Peclet number.
PMID- 27494699
TI - Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked
Responses in Olfactory Receptor Neurons.
AB - The influence of the sex steroid hormones progesterone and estradiol on
physiology and behavior during menstrual cycles and pregnancy is well known.
Several studies indicate that olfactory performance changes with cyclically
fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms
behind how female sex steroids modulate olfactory signaling is limited. A number
of different known genomic and non-genomic actions that are mediated by
progesterone and estradiol via interactions with different receptors may be
responsible for this modulation. Next generation sequencing-based RNA-Seq
transcriptome data from the murine olfactory epithelium (OE) and olfactory
receptor neurons (ORNs) revealed the expression of several membrane progestin
receptors and the estradiol receptor Gpr30. These receptors are known to mediate
rapid non-genomic effects through interactions with G proteins. RT-PCR and
immunohistochemical staining results provide evidence for progestin and estradiol
receptors in the ORNs. These data support the hypothesis that steroid hormones
are capable of modulating the odorant-evoked activity of ORNs. Here, we validated
this hypothesis through the investigation of steroid hormone effects by submerged
electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first
time, we demonstrate that the sex steroid hormones progesterone and estradiol
decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar
concentrations. Thus, both of these sex steroids can rapidly modulate the odor
responsiveness of ORNs through membrane progestin receptors and the estradiol
receptor Gpr30.
PMID- 27494703
TI - Current progress of Reelin in development, inflammation and tissue remodeling:
from nervous to visual systems.
AB - Reelin is a matrix glycoprotein that plays a pivotal role for the positioning of
neurons throughout brain development. In the early developing cortex Reelin
regulates radial migration of cortical neurons while later in development, Reelin
promotes maturation of dendrites and dendritic spines. Low Reelin levels
characterize healthy adult brain while increased Reelin levels have been
associated with cellular events underlying response to injury. Reelin has been
detected in structural and immune cells outside brain (liver, gut/colon tracts,
kidney, testis, ovary, lung, retina and cornea). In the Visual system, Reelin was
first described in the retina and thereafter in the cornea. Increased Reelin
levels were observed during retinogenesis, low levels were found in adulthood and
a significant increase was detected upon injury. Insult-driven Reelin changes
occur after upregulation of adhesion molecules, cytokines, neurotrophins, growth
factors, neuropeptides and other mediators as well as their receptors. These
soluble factors contribute to the development of nervous and visual system and
promote survival/recovery of neurons/accessory cells populating the injured
visual system. Likewise, Reelin might modulate these factors by driving different
multiple effects on homeostasis/plasticity, inflammation, healing and remodeling
at different physiopathological levels. Very low-density lipoprotein receptor,
apolipoprotein E receptor 2, integrins and the adaptor molecule Disabled 1
trigger Reelin. Recent advances highlight some Reelin activities during
inflammation and tissue remodeling and point out to a crucial Reelin activity in
the visual system. A better understanding of Reelin function in retinal
development might open to new attractive perspective for counteracting retina
degeneration.
PMID- 27494702
TI - The Arabidopsis Protein Phosphatase PP2C38 Negatively Regulates the Central
Immune Kinase BIK1.
AB - Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface
localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity
(PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of
several PRR complexes. How plant PTI is negatively regulated is not fully
understood. Here, we identify the protein phosphatase PP2C38 as a negative
regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically
associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co
receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the
phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative
burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on
serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1
activation. Together with our recent work on the control of BIK1 turnover, this
study reveals another important regulatory mechanism of this central immune
component.
PMID- 27494705
TI - A Preliminary Investigation of Ethnic Differences in Resistance in Multisystemic
Therapy.
AB - Therapy process research suggests that an inverted U-shaped trajectory of client
resistance, referred to as the struggle-and-working-through pattern, predicts
positive treatment outcomes. However, this research may lack external validity
given the exclusive focus on European Americans. This preliminary study explores
differences in resistance patterns in a sample of African American and European
American juvenile drug offenders and their families (n = 41) participating in
Multisystemic Therapy. Resistance was coded from session recordings at the
beginning, middle, and end of treatment. There were significant ethnic
differences in (a) mean resistance at midtreatment, (b) resistance trajectories,
and (c) predictive relationships between resistance trajectories and criminal
desistance. Notably, a negative quadratic (i.e., inverted U-shaped) resistance
trajectory was more characteristic of European Americans who desisted from crime,
whereas a positive quadratic (U-shaped) resistance pattern was more
characteristic of African Americans who desisted. There was no relationship
between resistance trajectory and later drug abstinence (i.e., cannabis). Within
the context of evidence-based therapies, core treatment processes may vary
significantly as a function of client ethnicity. We recommend that clinical
scientists make efforts to test for ethnic differences in treatment process so
that therapies like Multisystemic Therapy can be understood in a more
comprehensive and nuanced manner.
PMID- 27494704
TI - Kdm5/Lid Regulates Chromosome Architecture in Meiotic Prophase I Independently of
Its Histone Demethylase Activity.
AB - During prophase of the first meiotic division (prophase I), chromatin dynamically
reorganises to recombine and prepare for chromosome segregation. Histone
modifying enzymes are major regulators of chromatin structure, but our knowledge
of their roles in prophase I is still limited. Here we report on crucial roles of
Kdm5/Lid, one of two histone demethylases in Drosophila that remove one of the
trimethyl groups at Lys4 of Histone 3 (H3K4me3). In the absence of Kdm5/Lid, the
synaptonemal complex was only partially formed and failed to be maintained along
chromosome arms, while localisation of its components at centromeres was
unaffected. Kdm5/Lid was also required for karyosome formation and homologous
centromere pairing in prophase I. Although loss of Kdm5/Lid dramatically
increased the level of H3K4me3 in oocytes, catalytically inactive Kdm5/Lid can
rescue the above cytological defects. Therefore Kdm5/Lid controls chromatin
architecture in meiotic prophase I oocytes independently of its demethylase
activity.
PMID- 27494706
TI - Prevalence of Risk Factors for Cardiovascular Diseases in Bangladesh: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Given the rising incidence of cardiovascular diseases (CVDs) in
Bangladesh, an improved understanding of the epidemiology of CVD risk factors is
needed. Therefore, we reviewed published studies on CVD modifiable risk factors
e.g., Type 2 Diabetes Mellitus (T2DM), hypertension (HTN), dyslipidemia and
smoking as well as studies on CVDs and conducted a meta-analysis of risk factors
and disease prevalence. METHODS: We searched the GLOBAL HEALTH, MEDLINE, EMBASE
'BanglaJol' databases for all studies in English on CVDs and its associated
modifiable risk factors. Random effects meta-analysis methods were used to
estimate pooled prevalence. RESULTS: There were 74 eligible studies (outcome:
T2DM = 32, HTN = 24, dyslipidaemia = 8 and smoking = 25; CVDs = 10). Due to high
between study heterogeneity (p<0.001, I2> 95%) in the prevalence of CVD risk
factors, we presented median and interquartile range (IQR) instead of the pooled
estimates as the summary measures. Median (IQR) prevalence of T2DM, HTN,
dyslipidemia and smoking were 5.9% (1.97%-8.25%); 15.1% (10.52%-17.60%); 34.35%
(10.66%-48.50%) and 40.56% (0.80%-55.95%), respectively. The prevalence of T2DM
and dyslipidemia were significantly higher in urban compared to rural populations
(13.5 vs 6%, p<0.001; 41.5 vs 30%, p = 0.007, respectively). CONCLUSIONS: The
prevalence of risk factors for CVDs is high in Bangladesh, more so in urban
areas. Ageing of the population may be a factor but urbanization seems to have an
influence, possibly related to changes in dietary and physical activity patterns.
Further research, in particular longitudinal studies, is needed to explore the
complex interaction of these factors and to inform policies and programs for the
prevention and management of CVDs in Bangladesh.
PMID- 27494707
TI - Comparison of Two Commercial Automated Nucleic Acid Extraction and Integrated
Quantitation Real-Time PCR Platforms for the Detection of Cytomegalovirus in
Plasma.
AB - Quantitation of cytomegalovirus (CMV) viral load in the transplant patients has
become a standard practice for monitoring the response to antiviral therapy. The
cut-off values of CMV viral load assays for preemptive therapy are different due
to the various assay designs employed. To establish a sensitive and reliable
diagnostic assay for preemptive therapy of CMV infection, two commercial
automated platforms including m2000sp extraction system integrated the Abbott
RealTime (m2000rt) and the Roche COBAS AmpliPrep for extraction integrated COBAS
Taqman (CAP/CTM) were evaluated using WHO international CMV standards and 110
plasma specimens from transplant patients. The performance characteristics,
correlation, and workflow of the two platforms were investigated. The Abbott
RealTime assay correlated well with the Roche CAP/CTM assay (R2 = 0.9379,
P<0.01). The Abbott RealTime assay exhibited higher sensitivity for the detection
of CMV viral load, and viral load values measured with Abbott RealTime assay were
on average 0.76 log10 IU/mL higher than those measured with the Roche CAP/CTM
assay (P<0.0001). Workflow analysis on a small batch size at one time, using the
Roche CAP/CTM platform had a shorter hands-on time than the Abbott RealTime
platform. In conclusion, these two assays can provide reliable data for different
purpose in a clinical virology laboratory setting.
PMID- 27494708
TI - Perceived burdensomeness and suicide ideation in adult outpatients receiving
exposure therapy for anxiety disorders.
AB - Perceived burdensomeness is considered a proximal risk factor for suicide
ideation. However, there is a lack of prospective studies. Furthermore, it is
unclear in as much psychotherapy for anxiety disorders is associated with a
decrease in suicide ideation. A total of 105 adult outpatients suffering from
panic disorder, agoraphobia, or specific phobia received manualized exposure
therapy. Perceived burdensomeness was considered as predictor of suicide ideation
concurrently, after the fourth and the tenth therapy session and posttreatment -
controlling for baseline symptom distress, suicide ideation, number of therapy
sessions and age. Furthermore, pre-to post-changes in suicide ideation and
perceived burdensomeness were assessed. Perceived burdensomeness emerged as a
significant predictor of suicidal ideation concurrently and after the fourth and
the tenth therapy session, but not at the end of therapy. Treatment had no effect
on suicide ideation and only a marginal effect on perceptions of burdensomeness.
In conclusion, the current study highlights the importance of perceptions of
burdensomeness in understanding suicide ideation.
PMID- 27494709
TI - Progress and potential of RAS mutation detection for diagnostics and companion
diagnostics.
AB - INTRODUCTION: The importance of RAS mutation in carcinogenesis is established,
and knowledge of an individual cancer's mutation status is important for optimal
treatment. Areas covered: This paper is restricted to RAS testing in cancer, and
highlights papers relevant to current practice. Expert commentary: Multiple
laboratory methods are available for RAS gene analysis. PCR is commonly used to
determine RAS status, providing a robust and inexpensive technology for clinical
use. Next generation sequencing (NGS) platforms are changing the way in which
mutation status is determined, though they require considerable expertise. Pre
analytical issues affect both methods and should be considered. The
interpretation and reporting of results is not simple, particularly for NGS.
External quality assurance is a pre-requisite for success, and is mandated by
most laboratory accreditation schemes. The use of RAS testing is now extending
beyond biopsy material to include the detection of mutations in circulating cell
free DNA and tumour cells.
PMID- 27494710
TI - The translation factors of Drosophila melanogaster.
AB - Synthesis of polypeptides from mRNA (translation) is a fundamental cellular
process that is coordinated and catalyzed by a set of canonical 'translation
factors'. Surprisingly, the translation factors of Drosophila melanogaster have
not yet been systematically identified, leading to inconsistencies in their
nomenclature and shortcomings in functional (Gene Ontology, GO) annotations.
Here, we describe the complete set of translation factors in D. melanogaster,
applying nomenclature already in widespread use in other species, and revising
their functional annotation. The collection comprises 43 initiation factors, 12
elongation factors, 3 release factors and 6 recycling factors, totaling 64 of
which 55 are cytoplasmic and 9 are mitochondrial. We also provide an overview of
notable findings and particular insights derived from Drosophila about these
factors. This catalog, together with the incorporation of the improved
nomenclature and GO annotation into FlyBase, will greatly facilitate access to
information about the functional roles of these important proteins.
PMID- 27494712
TI - Reactivity and Properties of Metal Complexes Enabled by Flexible and Redox-Active
Ligands with a Ferrocene Backbone.
AB - Our group has focused on the organometallic chemistry of rare-earth metals and
actinides for a decade. By installing ferrocenediamide ligands at electropositive
metal centers, we have been able to disclose unprecedented reactivity toward
aromatic N-heterocycles, arenes, and other small molecules such as P4. Systematic
studies employing X-ray crystallography, spectroscopy, cyclic voltammetry, and
density functional theory calculations revealed that the ferrocene backbone could
stabilize the electron-deficient metal through a donor-acceptor-type interaction.
Most noteworthy is that this interaction can be readily turned on or off by the
addition or removal of a Lewis base. In addition to its flexible coordination,
the redox-active nature of the ferrocene backbone enabled us to explore redox
switchable transformations. The introduction of ferrocene-based ligands into
organolanthanide chemistry not only helped us to study intriguing fundamental
problems but also led to fruitful chemistry including small-molecule activation
and controlled copolymerization reactions.
PMID- 27494711
TI - Cilostazol Modulates Autophagic Degradation of beta-Amyloid Peptide via SIRT1
Coupled LKB1/AMPKalpha Signaling in Neuronal Cells.
AB - A neuroprotective role of autophagy mediates the degradation of beta-amyloid
peptide (Abeta) in Alzheimer's disease (AD). The previous study showed cilostazol
modulates autophagy by increasing beclin1, Atg5 and LC3-II expressions, and
depletes intracellular Abeta accumulation. This study elucidated the mechanisms
through which cilostazol modulates the autophagic degradation of Abeta in
neurons. In N2a cells, cilostazol (10-30 MUM), significantly increased the
expression of P-AMPKalpha (Thr 172) and downstream P-ACC (acetyl-CoA carboxylase)
(Ser 79) as did resveratrol (SIRT1 activator), or AICAR (AMPK activator), which
were blocked by KT5720, compound C (AMPK inhibitor), or sirtinol. Furthermore,
phosphorylated-mTOR (Ser 2448) and phosphorylated-P70S6K (Thr 389) expressions
were suppressed, and LC3-II levels were elevated in association with decreased
P62/Sqstm1 by cilostazol. Cilostazol increased cathepsin B activity and decreased
p62/SQSTM 1, consequently decreased accumulation of Abeta1-42 in the activated
N2aSwe cells, and these results were blocked by sirtinol, compound C and
bafilomycin A1 (autophagosome blocker), suggesting enhanced autophagosome
formation by cilostazol. In SIRT1 gene-silenced N2a cells, cilostazol failed to
increase the expressions of P-LKB1 (Ser 428) and P-AMPKalpha, which contrasted
with its effect in negative control cells transfected with scrambled siRNA
duplex. Further, N2a cells transfected with expression vectors encoding pcDNA
SIRT1 showed increased P-AMPKalpha expression, which mimicked the effect of
cilostazol in N2a cells; suggesting cilostazol-stimulated expressions of P-LKB1
and P-AMPKalpha were SIRT1-dependent. Unlike their effects in N2a cells, in HeLa
cells, which lack LKB1, cilostazol and resveratrol did not elevate SIRT1 or P
AMPKalpha expression, indicating cilostazol and resveratrol-stimulated
expressions of SIRT1 and P-AMPKalpha are LKB1-dependent. In conclusion,
cilostazol upregulates autophagy by activating SIRT1-coupled P-LKB1/P-AMPKalpha
and inhibiting mTOR activation, thereby decreasing Abeta accumulation.
PMID- 27494714
TI - Health and social conditions in Norwegian polio survivors: A 20-year follow-up
study.
AB - OBJECTIVE: To explore the physical and social situation of the Norwegian polio
population in 2014, and to compare the status of this population in 2014 with the
results of a similar survey carried out 20 years previously, in 1994. DESIGN: The
study was based on a questionnaire covering demographics, polio history, and
current medical, psychological and social conditions. SUBJECTS: The questionnaire
was prepared in cooperation with the National Society of Polio Survivors and
others with known polio (n = 1,968). A total of 1,408 persons responded (72%),
mean age 70 years (range 28-98 years). RESULTS: The most frequent health problems
reported were muscle and joint pain, cold intolerance and insomnia. New muscle
weakness and loss of muscle volume were reported more frequently in 2014 than in
the 1994 study. The use of orthopaedic aids, assistive devices, ventilators and
other respiratory aids had increased significantly, but 83% reported that they
still had no home care or nursing services support. The 2014 polio population
reported only minor subjective worsening of health and well-being compared with
the 1994 cohort. CONCLUSION: The present study indicates that the elderly polio
population are experiencing new muscle weakness and increasing health problems,
but that the deterioration occurs slowly and with fewer consequences for the
subjective experience of general health and well-being, indicating that the
patients are adapting to their life situation. However, subgroups of the elderly
polio population are in need of special care.
PMID- 27494715
TI - Study of Robustness in Functionally Identical Coupled Networks against Cascading
Failures.
AB - Based on coupled networks, taking node load, capacity and load redistribution
between two networks into consideration, we propose functionally identical
coupled networks, which consist of two networks connected by interlinks.
Functionally identical coupled networks are derived from the power grid of the
United States, which consists of many independent grids. Many power transmission
lines are planned to interconnect those grids and, therefore, the study of the
robustness of functionally identical coupled networks becomes important. In this
paper, we find that functionally identical coupled networks are more robust than
single networks under random attack. By studying the effect of the broadness and
average degree of the degree distribution on the robustness of the network, we
find that a broader degree distribution and a higher average degree increase the
robustness of functionally identical coupled networks under random failure. And
SF-SF (two coupled scale-free networks) is more robust than ER-ER (two coupled
random networks) or SF-ER (coupled random network and scale-free network). This
research is useful to construct robust functionally identical coupled networks
such as two cooperative power grids.
PMID- 27494713
TI - Amplification of TGFbeta Induced ITGB6 Gene Transcription May Promote Pulmonary
Fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a devastating, progressive disease with
poor survival rates and limited treatment options. Upregulation of alphavbeta6
integrins within the alveolar epithelial cells is a characteristic feature of IPF
and correlates with poor patient survival. The pro-fibrotic cytokine TGFbeta1 can
upregulate alphavbeta6 integrin expression but the molecular mechanisms driving
this effect have not previously been elucidated. We confirm that stimulation with
exogenous TGFbeta1 increases expression of the integrin beta6 subunit gene
(ITGB6) and alphavbeta6 integrin cell surface expression in a time- and
concentration-dependent manner. TGFbeta1-induced ITGB6 expression occurs via
transcriptional activation of the ITGB6 gene, but does not result from effects on
ITGB6 mRNA stability. Basal expression of ITGB6 in, and alphavbeta6 integrins on,
lung epithelial cells occurs via homeostatic alphavbeta6-mediated TGFbeta1
activation in the absence of exogenous stimulation, and can be amplified by
TGFbeta1 activation. Fundamentally, we show for the first time that TGFbeta1
induced ITGB6 expression occurs via canonical Smad signalling since dominant
negative constructs directed against Smad3 and 4 inhibit ITGB6 transcriptional
activity. Furthermore, disruption of a Smad binding site at -798 in the ITGB6
promoter abolishes TGFbeta1-induced ITGB6 transcriptional activity. Using
chromatin immunoprecipitation we demonstrate that TGFbeta1 stimulation of lung
epithelial cells results in direct binding of Smad3, and Smad4, to the ITGB6 gene
promoter within this region. Finally, using an adenoviral TGFbeta1 over
expression model of pulmonary fibrosis we demonstrate that Smad3 is crucial for
TGFbeta1-induced alphavbeta6 integrin expression within the alveolar epithelium
in vivo. Together, these data confirm that a homeostatic, autocrine loop of
alphavbeta6 integrin activated TGFbeta1-induced ITGB6 gene expression regulates
epithelial basal alphavbeta6 integrin expression, and demonstrates that this
occurs via Smad-dependent transcriptional regulation at a single Smad binding
site in the promoter of the beta6 subunit gene. Active TGFbeta1 amplifies this
pathway both in vitro and in vivo, which may promote fibrosis.
PMID- 27494717
TI - Molecular Cloning and Functional Expression of a Delta9- Fatty Acid Desaturase
from an Antarctic Pseudomonas sp. A3.
AB - Fatty acid desaturase enzymes play an essential role in the synthesis of
unsaturated fatty acids. Pseudomonas sp. A3 was found to produce a large amount
of palmitoleic and oleic acids after incubation at low temperatures. Using
polymerase Chain Reaction (PCR), a novel Delta9- fatty acid desaturase gene was
isolated, cloned, and successfully expressed in Escherichia coli. The gene was
designated as PA3FAD9 and has an open reading frame of 1,185 bp which codes for
394 amino acids with a predicted molecular weight of 45 kDa. The activity of the
gene product was confirmed via GCMS, which showed a functional putative Delta9
fatty acid desaturase capable of increasing the total amount of cellular
unsaturated fatty acids of the E. coli cells expressing the gene. The results
demonstrate that the cellular palmitoleic acids have increased two-fold upon
expression at 15 degrees C using only 0.1 mM IPTG. Therefore, PA3FAD9 from
Pseudomonas sp.A3 codes for a Delta9-fatty acid desaturase-like protein which was
actively expressed in E. coli.
PMID- 27494716
TI - MicroRNA Profiling in the Medial and Lateral Habenula of Rats Exposed to the
Learned Helplessness Paradigm: Candidate Biomarkers for Susceptibility and
Resilience to Inescapable Shock.
AB - Depression is a highly heterogeneous disorder presumably caused by a combination
of several factors ultimately causing the pathological condition. The genetic
liability model of depression is likely to be of polygenic heterogeneity. miRNAs
can regulate multiple genes simultaneously and therefore are candidates that
align with this model. The habenula has been linked to depression in both
clinical and animal studies, shifting interest towards this region as a neural
substrate in depression. The goal of the present study was to search for
alterations in miRNA expression levels in the medial and lateral habenula of rats
exposed to the learned helplessness (LH) rat model of depression. Ten miRNAs
showed significant alterations associating with their response to the LH
paradigm. Of these, six and four miRNAs were significantly regulated in the MHb
and LHb, respectively. In the MHb we identified miR-490, miR-291a-3p, MiR-467a,
miR-216a, miR-18b, and miR-302a. In the LHb miR-543, miR-367, miR-467c, and miR
760-5p were significantly regulated. A target gene analysis showed that several
of the target genes are involved in MAPK signaling, neutrophin signaling, and
ErbB signaling, indicating that neurotransmission is affected in the habenula as
a consequence of exposure to the LH paradigm.
PMID- 27494718
TI - Astroglia in Thick Tissue with Super Resolution and Cellular Reconstruction.
AB - We utilized the recently published method of passive CLARITY to explore brain
astrocytes for the first time with our optimized method. Astrocytes are the
fundamental cells in the brain that act to maintain the synaptic activity of
neurons, support metabolism of all neurons, and communicate through extensive
networks throughout the CNS. They are the defining cell that differentiates lower
organisms from humans. From a disease vantage point they are the principal cause
of brain tumors and the propagator of neurodegenerative diseases like amyotrophic
lateral sclerosis. New methods to study these cells is paramount. Our modified
use of CLARITY provides a new way to study these brain cells. To reduce cost,
speed up tissue clearing process, reduce human handling error, and to retrieve
quantifiable data from single confocal and pseudo-super resolution microscopy we
modified and optimized the original protocol.
PMID- 27494719
TI - A Protocolised Once a Day Modified Early Warning Score (MEWS) Measurement Is an
Appropriate Screening Tool for Major Adverse Events in a General Hospital
Population.
AB - BACKGROUND: The Modified Early Warning Score (MEWS) was developed to timely
recognise clinically deteriorating hospitalised patients. However, the ability of
the MEWS in predicting serious adverse events (SAEs) in a general hospital
population has not been examined prospectively. The aims were to (1) analyse
protocol adherence to a MEWS protocol in a real-life setting and (2) to determine
the predictive value of protocolised daily MEWS measurement on SAEs: death,
cardiac arrests, ICU-admissions and readmissions. METHODS: All adult patients
admitted to 6 hospital wards in October and November 2015 were included. MEWS
were checked each morning by the research team. For each critical score (MEWS >=
3), the clinical staff was inquired about the actions performed. 30-day follow-up
for SAEs was performed to compare between patients with and without a critical
score. RESULTS: 1053 patients with 3673 vital parameter measurements were
included, 200 (19.0%) had a critical score. The protocol adherence was 89.0%.
18.2% of MEWS were calculated wrongly. Patients with critical scores had
significant higher rates of unplanned ICU admissions [7.0% vs 1.3%, p < 0.001],
in-hospital mortality [6.0% vs 0.8%, p < 0.001], 30-day readmission rates [18.6%
vs 10.8%, p < 0.05], and a longer length of stay [15.65 (SD: 15.7 days) vs 6.09
(SD: 6.9), p < 0.001]. Specificity of MEWS related to composite adverse events
was 83% with a negative predicting value of 98.1%. CONCLUSIONS: Protocol
adherence was high, even though one-third of the critical scores were calculated
wrongly. Patients with a MEWS >= 3 experienced significantly more adverse events.
The negative predictive value of early morning MEWS < 3 was 98.1%, indicating the
reliability of this score as a screening tool.
PMID- 27494720
TI - Quantitative image analysis to characterize the dynamics of Listeria
monocytogenes biofilms.
AB - This work shows that the combination of two-dimensional (2D) and three
dimensional (3D) analyses of images acquired by confocal laser scanning
microscopy facilitates the quantitative spatiotemporal characterization of
architectures formed by Listeria monocytogenes biofilms. In particular, the
analysis of structural features such as maximum thickness, biovolume, areal
porosity and maximum diffusion distance allowed elucidating differences in
biofilm formation of three L. monocytogenes strains (L1A1, CECT5873 and
CECT4032). The analysis showed a common sequence for all strains. In the first
phase, independent clusters evolve to interconnected clusters and honeycomb-like
structures. Flat biofilms characterized the second phase. The structures
disappear in the third phase. Nevertheless, the duration of the phases differed
from strain to strain. L1A1 strain exhibited the slowest dynamics and the
thickest biofilms while the strain CECT4032 presented the faster dynamics and the
thinnest biofilms. Also, the number of dead cells varies significantly from
strain to strain. From the results of the analysis, it can be concluded that 2D
parameters are critical to differentiating morphological features while 3D
parameters ease the interpretation and comparative study of the different phases
during the life cycle of biofilms.
PMID- 27494722
TI - Clinical value of drug-coated balloon angioplasty for de novo lesions in patients
with coronary artery disease.
AB - BACKGROUND: Despite the low restenosis rates of drug-eluting stents (DES),
several problems remain, including stent thrombosis, stent fracture, and neo
atherosclerosis. 'Stent-less' (balloon alone) percutaneous coronary intervention
(PCI) is still being used, and several clinical trials have supported the
efficacy of DCB. The aim of this study was to investigate the efficacy of a drug
coated balloon (DCB) in the treatment of de novo coronary artery disease.
METHODS: We enrolled 60 consecutive patients who had been given elective PCI
between May 2014 and June 2015. They were randomly assigned to a 'stent-less'
group (n=30) and a 'stent' group (n=30). Twenty-seven patients were treated with
DCB alone and 33 with DES, and then evaluated for target lesion revascularization
(TLR) rate and by quantitative coronary angiography (QCA) eight months later.
RESULTS: TLR rates were similar in the two groups (DCB; 0.0%, DES; 6.1%,
P=0.169). In the QCA analysis, minimal lumen diameter (MLD) and acute gain were
significantly smaller in the DCB group than in the DES group immediately after
PCI (2.36+/-0.46 vs 2.64+/-0.37, P=0.011, and 1.63+/-0.41 vs 2.08+/-0.37,
P<0.0001, respectively). Eight months after PCI, however, there was no
significant difference in MLD or late lumen loss between the two groups.
CONCLUSIONS: A 'stent-less' PCI using DCB could be useful even in the DES era.
After 'stent-less' PCI, antiplatelet agents might be reduced or discontinued more
safely than after DES implantation.
PMID- 27494721
TI - Differential left-to-right atria gene expression ratio in human sinus rhythm and
atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis.
AB - BACKGROUND: Atrial fibrillation (AF) causes atrial remodeling, and the left
atrium (LA) is the favored substrate for maintaining AF. It remains unclear if AF
remodels both atria differently and contributes to LA arrhythmogenesis and
thrombogenesis. Therefore, we wished to characterize the transcript profiles in
the LA and right atrium (RA) in sinus rhythm (SR) and AF respectively. METHODS:
Paired LA and RA appendages acquired from patients receiving cardiac surgery were
used for ion-channel- and whole-exome-based transcriptome analysis. The
ultrastructure was evaluated by immunohistochemistry. RESULTS: Twenty-two and
twenty ion-channels and transporters were differentially expressed between the LA
and RA in AF and SR, respectively. Among these, 15 genes were differentially
expressed in parallel between AF and SR. AF was associated with increased LA/RA
expression ratio in 9 ion channel-related genes, including genes related to
calcium handling. In microarray, AF was associated with a differential LA/RA gene
expression ratio in 309 genes, and was involved in atherosclerosis-related
signaling. AF was associated with the upregulation of thrombogenesis-related
genes in the LA appendage, including P2Y12, CD 36 and ApoE. Immunohistochemistry
showed higher expressions of collagen-1, oxidative stress and TGF-beta1 in the RA
compared to the LA. CONCLUSIONS: AF was associated with differential LA-to-RA
gene expression related to specific ion channels and pathways as well as
upregulation of thrombogenesis-related genes in the LA appendage. Targeting the
molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling
in the LA appendage may help provide new therapeutic options in treating AF and
preventing thromboembolism in AF.
PMID- 27494723
TI - Therapeutic efficacy of PCSK9 monoclonal antibodies in statin-nonresponsive
patients with hypercholesterolemia and dyslipidemia: A systematic review and meta
analysis.
AB - BACKGROUND AND OBJECTIVE: Heterozygous familial hypercholesterolemia and
dyslipidemia are the predominant causes for cardiovascular disease (CVD).
Clinical guidelines for lowering CVD risk have advocated that low density
lipoprotein-cholesterol (LDL-C) must be reduced. The primary choice of therapy
for controlling lipidemia has been statins, which are not completely effective.
Proprotein convertase subtilisin/kexin type-9 (PCSK9), which interferes with LDL
clearance from circulation, inversely relates to the LDL-C levels. The loss of
statin efficacy is likely due to increased circulating PCSK9 and antibody therapy
against PCSK9 has been found to be efficacious in lowering LDL-C. In this study,
we evaluated the efficacy of PCSK9-mAbs for lowering LDL-C, in statin non
responsive hypercholesterolemia patients. STUDY DESIGN AND METHODS: PubMed,
EMBASE, Scholar, Web of Science and Scopus databases were searched to identify
randomized controlled trials of PCSK9 antibody-statin combination vs statin,
published till 2015. Two reviewers independently screened the articles, and a
collective decision was reached about the included studies in the metaanalysis.
Parameters analyzed: change from baseline in LDL-C, high-density lipoprotein
cholesterol (HDL-C) and total cholesterol (TC); ApoB and ApoA1 levels. RESULTS: A
total of 12 studies with 4909 patients were selected. Overall, add-on therapy
with PCSK9-mAb to the ongoing statin therapy was found to achieve greater
reduction in LDL-C, ApoB, TC, compared to statin therapy. There were no major
treatment emergent adverse effects due to PCSK9-mAb therapy. CONCLUSIONS: In
adult patients with heterozygous familial hypercholesterolemia and dyslipidemia,
PCSK9-mAb therapy in combination with statins was able to achieve the goal of
lowering LDL-C.
PMID- 27494724
TI - A case of initial rhythm of pulseless electrical activity caused by vasospastic
angina.
PMID- 27494725
TI - Iron deficiency in heart failure: Impact on response to cardiac resynchronization
therapy.
PMID- 27494726
TI - Refractory torsade de pointes induced by terlipressin (Glypressin).
PMID- 27494727
TI - Guide extension, unmissable tool in the armamentarium of modern interventional
cardiology. A comprehensive review.
AB - Due to the aging population undergoing percutaneous coronary intervention (PCI),
interventional cardiologists are confronted daily with treatment of lesions with
complex anatomy. Despite improvements in stent devices and PCI techniques, these
lesions remain a challenge in terms of procedural success. Guide-extensions (GE)
are coaxial "mother and child" catheters employed to facilitate device delivery
but they can be used in many different complex scenarios. A comprehensive review
of the possible applications of GE and of the GuideLinerTM (GL), the most widely
used GE device, is missing. We therefore aim to provide a comprehensive review of
all the potential applications of the GL and other GE devices, describe its
limitations as well as tips and tricks for successful usage of this GE catheter.
PMID- 27494728
TI - The impact of T786C and G894T polymorphisms of eNOS on vascular endothelial
growth factor serum levels in type 2 diabetes patients.
PMID- 27494729
TI - An anterior left ventricular lead position is associated with increased mortality
and non-response in cardiac resynchronization therapy.
AB - BACKGROUND: Non-response to cardiac resynchronization therapy (CRT) might be due
to insufficient resynchronization as a result of a sub-optimal left ventricular
lead positon (LV-LP). OBJECTIVE: To evaluate the impact of different LV-LPs on
mortality and symptomatic improvement in a large cohort of patients treated with
CRT. METHODS: We performed a nationwide cohort study on consecutive patients
receiving a CRT device from 1997 to 2012 registered in the Danish pacemaker and
ICD register. The LV-LP was defined clockwise in a left anterior oblique (LAO)
view and categorized as anterior (<=2 o'clock), lateral (2 to 4 o'clock) or
posterior (>4 o'clock), and as basal, mid-ventricular, or apical in a right
anterior oblique (RAO) view. Outcomes were all cause mortality and clinical
response (improvement in NYHA class). Adjusted hazard ratio (aHR) and odds ratio
(aOR) with 95% confidence intervals (CI) were calculated using Cox and logistic
regression analysis. RESULTS: A total of 2594 patients were included. A lateral
LV-LP, (aHR 0.77, 95% CI 0.64-0.92, p=0.004), and a posterior LV-LP, (aHR 0.71
95% CI 0.53-0.97, p=0.029) were associated with lower mortality as compared to an
anterior LV-LP. A lateral LV-PV was associated with higher clinical response rate
as compared to an anterior LV-LP (aOR 1.37, 1.03-1.83, p=0.032). No statistically
significant associations were observed between LV-LP in the RAO view and
mortality or clinical response. CONCLUSION: An anterior left ventricular lead
position is associated with increased all-cause mortality and lower clinical
response rate in patients treated with CRT and should be avoided.
PMID- 27494730
TI - Atrial natriuretic peptide therapy and in-hospital mortality in acute myocardial
infarction patients undergoing percutaneous coronary intervention.
AB - BACKGROUND: Atrial natriuretic peptide (ANP) therapy has been reported to have
beneficial effects in patients with acute myocardial infarction (AMI); however,
its impact on in-hospital mortality remains unclear. This study aimed to
investigate the effects of ANP therapy on in-hospital mortality in AMI patients
undergoing percutaneous coronary intervention (PCI). METHODS: This was a
retrospective cohort study using the Diagnosis Procedure Combination inpatient
database in Japan. We identified AMI patients who underwent PCI with stent
implantation on the day of admission, between 2010 and 2014. We compared 30-day
in-hospital mortality between patients who started ANP therapy on the day of
admission (ANP group) and those who received no ANP therapy during
hospitalization (control group), using propensity score and instrumental variable
methods. RESULTS: Of 60,592 eligible patients (8189 ANP group, 52,403 control
group) from 850 hospitals, 1:1 propensity score matching created 8027 pairs.
There was no significant difference in 30-day in-hospital mortality between the
ANP and control groups (3.4% vs. 3.8%, respectively; p=0.162; risk difference,
0.42%; 95% confidence interval [CI], -1.00% to 0.15%) in the propensity score
matched cohort. Logistic regression analysis with adjustment for propensity score
deciles found no significant association between ANP therapy and 30-day in
hospital mortality (odds ratio, 0.99; 95% CI, 0.82 to 1.19). Instrumental
variable analysis also showed no significant association between ANP therapy and
30-day in-hospital mortality (risk difference, -0.59%; 95% CI, -1.24% to 0.05%).
CONCLUSIONS: This study found no significant association between ANP therapy and
in-hospital mortality in AMI patients undergoing PCI.
PMID- 27494731
TI - No evidence of adverse cardiac remodeling in former elite endurance athletes.
AB - BACKGROUND: The impact of high exercise loads on a previously healthy heart
remains controversial. We examined the consequences of decades of strenuous
endurance exercise at the highest competition level on heart dimensions and
volumes as well as on serum biomarkers of cardiac fibrosis/remodeling. METHODS
AND RESULTS: We compared echocardiographic measurements and serum biomarkers of
cardiac fibrosis/remodeling [troponin I, galectin-3, matrix metallopeptidase-2
and -9, N-terminal pro-brain natriuretic peptide, carboxy-terminal propeptide of
type I procollagen, and soluble suppressor of tumorigenicity-2 (sST
2)/interleukin(IL)-1R4] in 53 male athletes [11 former professional ('elite') and
42 amateur-level ('sub-elite') cyclists or runners, aged 40-70years] and 18 aged
matched controls. A subset of 15 subjects (5 controls, 3 sub-elite and 7 elite
athletes) also underwent cardiac magnetic resonance imaging (cMRI). Elite and sub
elite athletes had greater echocardiography-determined left ventricular
myocardial mass indexed to body surface area than controls (113+/-22, 115.2+/
23.1 and 94.8+/-21g/m(2), respectively, p=0.008 for group effect), with similar
results for left (50.5+/-4.4, 48.2+/-4.3 and 46.4+/-5.2mm, p=0.008) and right
(38.6+/-3.8, 41.1+/-5.5 and 34.7+/-4.3mm, p<0.001) ventricular end-diastolic
diameter, and cMRI-determined left atrial volume indexed to body surface area
(62.7+/-8.1, 56.4+/-16.0 and 39.0+/-14.1ml/m(2), p=0.026). Two athletes showed a
non-coronary pattern of small, fibrotic left ventricular patches detected by late
gadolinium enhancement. No group effect was noted for biomarkers. CONCLUSIONS:
Regardless of their competition level at a younger age, veteran endurance
athletes showed an overall healthy, non-pathological pattern of cardiac
remodeling. Nonetheless, the physiopathology of the ventricular fibrotic patches
detected warrants further investigation.
PMID- 27494732
TI - Improved Accuracy in RNA-Protein Rigid Body Docking by Incorporating Force Field
for Molecular Dynamics Simulation into the Scoring Function.
AB - RNA-protein interactions play fundamental roles in many biological processes. To
understand these interactions, it is necessary to know the three-dimensional
structures of RNA-protein complexes. However, determining the tertiary structure
of these complexes is often difficult, suggesting that an accurate rigid body
docking for RNA-protein complexes is needed. In general, the rigid body docking
process is divided into two steps: generating candidate structures from the
individual RNA and protein structures and then narrowing down the candidates. In
this study, we focus on the former problem to improve the prediction accuracy in
RNA-protein docking. Our method is based on the integration of physicochemical
information about RNA into ZDOCK, which is known as one of the most successful
computer programs for protein-protein docking. Because recent studies showed the
current force field for molecular dynamics simulation of protein and nucleic
acids is quite accurate, we modeled the physicochemical information about RNA by
force fields such as AMBER and CHARMM. A comprehensive benchmark of RNA-protein
docking, using three recently developed data sets, reveals the remarkable
prediction accuracy of the proposed method compared with existing programs for
docking: the highest success rate is 34.7% for the predicted structure of the RNA
protein complex with the best score and 79.2% for 3,600 predicted ones. Three
full atomistic force fields for RNA (AMBER94, AMBER99, and CHARMM22) produced
almost the same accurate result, which showed current force fields for nucleic
acids are quite accurate. In addition, we found that the electrostatic
interaction and the representation of shape complementary between protein and RNA
plays the important roles for accurate prediction of the native structures of RNA
protein complexes.
PMID- 27494733
TI - Molecular Genetic Approaches for Environmental Stress Tolerant Crop Plants:
Progress and Prospects.
AB - BACKGROUND: Global food security is threatened by the severe environmental
conditions that have reduced the worldwide crop yield. Plants possess inherent
mechanisms to cope with the initial stress phase but to ensure their survival
through harsh climate, the intervention of genetic engineering is desirable.
OBJECTIVE: We present a comprehensive review on the progress made in the field of
developing environmental stress tolerant crops and the prospects that can be
undertaken for achieving it. METHODS: We review the effects of abiotic and biotic
stresses on crop plants, and the use of different molecular genetic approaches to
cope with these environmental stresses for establishment of sustainable
agriculture. The various strategies employed in different crops have also been
discussed. We also summarized the major patents in the field of plant stress
tolerance that have been granted in the last five years. RESULTS: On the basis of
these analyses, we propose that genetic engineering of crops is the preferred
approach over the traditional methods for yielding healthier and viable
agriculture in response to the different stressful environments. The wild
progenitors of cultivated crop species can prove to be highly potential genetic
resources in this regard and can be exploited to produce better crops that are
relatively tolerant towards various environmental stresses. CONCLUSION: Thus,
elucidation of genetic loci and deciphering the underlying mechanisms that confer
tolerance to plants against stressful conditions followed by its successful
introgression into elite, high-yielding crop varieties can be an effective way to
engineer the crops for sustainable agriculture.
PMID- 27494734
TI - Inactivation of Pseudomonas aeruginosa by Chitosan Coated Iron Oxide
Nanoparticles.
AB - BACKGROUND: Pseudomonas aeruginosa is one of the potent opportunistic pathogens
associated with respiratory and urinary tract infection. The bacterium owes its
pathogenicity due to the intrinsic resistance to antibiotics and disinfectants.
OBJECTIVE: The present study is focused on the synthesis of antibacterial
chitosan coated iron oxide nanoparticles for rapid inactivation of Pseudomonas
aeruginosa. We have discussed the relevant patents on synthesis and antibacterial
potential of metallic nanoparticles and chitosan. METHOD: Chitosan coated iron
oxide nanoparticles were synthesized by coprecipitation method at room
temperature using non-toxic chitosan and iron salts in alkali media. The
particles were characterized and evaluated for antibacterial property against
Pseudomonas aeruginosa. RESULTS: The average size of the particles was measured
as 52 nm. The surface area of the coated particles was as high as 90 +/-5 m2/g.
FTIR spectra confirmed the coating of chitosan on nanoparticles. The coated
particles showed excellent antibacterial activity against the bacteria. The
minimum inhibitory concentration of the coated particles was 105)ug mol-1. The
morphological alteration and cytoplasmic leakage of bacteria were confirmed by
SEM image and release of intracellular constituents, respectively. Higher 260 nm
absorbance value confirmed stronger antibacterial activity of the coated
nanoparticles as compared to pure chitosan and bare iron oxide nanoparticles.
CONCLUSION: The study indicated that chitosan coated iron oxide nanoparticles
have superior antibacterial property as compared to pure chitosan and iron oxide
nanoparticles.
PMID- 27494735
TI - Preparation and Biochemical Property of Penicillin G Amidase-Loaded Alginate and
Alginate/Chitosan Hydrogel Beads.
AB - BACKGROUND: Penicillin G amidase (PGA) (EC 3.5.1.11) are enzymes that are mainly
involved in the synthesis of semi-synthetic }-lactam antibiotics. Soluble PGA is
costly and lacks long term operational stability. We revised most of the patents
related to Penicillin G amidase (PGA) immobilization in the section "Recent
Patents on Immobilized Penicillin G Amidase". OBJECTIVE: The aim of this work was
to study comparative biochemical property of PGA enzyme immobilized in two hydro
gel beads - Ca-alginate and alginate+chitosan hybrid and morphologically
characterised by SEM. METHODS: PGA immobilized in alginate+chitosan hybrid bead
shows high pH and thermal stability. Km, Vmax and Effectiveness factor (1) value
of free PGA were 56.19 mg/ml, 1.786 U/ml and 1, respectively. These parameters
for PGA immobilized alginate beads were 64.84 mg/ml, 0.781U/ml and 0.437,
respectively and for PGA immobilized alginate+chitosan hybrid beads were 87.08
mg/ml, 0.622 U/ml and 0.348, respectively. RESULTS: Immobilized PGA on
alginate+chitosan hybrid beads gave the highest thermal stability, reusability
and storage stability than alginate immobilized PGA. CONCLUSION: The entrapment
of PGA on alginate+chitosan hybrid beads revealed several advantages and could be
used in 6APA (6- aminopenicillanic acid) production.
PMID- 27494736
TI - Phenotypic Characterization of Toxic Compound Effects on Liver Spheroids Derived
from iPSC Using Confocal Imaging and Three-Dimensional Image Analysis.
AB - Cell models are becoming more complex to better mimic the in vivo environment and
provide greater predictivity for compound efficacy and toxicity. There is an
increasing interest in exploring the use of three-dimensional (3D) spheroids for
modeling developmental and tissue biology with the goal of accelerating
translational research in these areas. Accordingly, the development of high
throughput quantitative assays using 3D cultures is an active area of
investigation. In this study, we have developed and optimized methods for the
formation of 3D liver spheroids derived from human iPS cells and used those for
toxicity assessment. We used confocal imaging and 3D image analysis to
characterize cellular information from a 3D matrix to enable a multi-parametric
comparison of different spheroid phenotypes. The assay enables characterization
of compound toxicities by spheroid size (volume) and shape, cell number and
spatial distribution, nuclear characterization, number and distribution of cells
expressing viability, apoptosis, mitochondrial potential, and viability marker
intensities. In addition, changes in the content of live, dead, and apoptotic
cells as a consequence of compound exposure were characterized. We tested 48
compounds and compared induced pluripotent stem cell (iPSC)-derived hepatocytes
and HepG2 cells in both two-dimensional (2D) and 3D cultures. We observed
significant differences in the pharmacological effects of compounds across the
two cell types and between the different culture conditions. Our results indicate
that a phenotypic assay using 3D model systems formed with human iPSC-derived
hepatocytes is suitable for high-throughput screening and can be used for
hepatotoxicity assessment in vitro.
PMID- 27494737
TI - The Complexity of Dynamics in Small Neural Circuits.
AB - Mean-field approximations are a powerful tool for studying large neural networks.
However, they do not describe well the behavior of networks composed of a small
number of neurons. In this case, major differences between the mean-field
approximation and the real behavior of the network can arise. Yet, many
interesting problems in neuroscience involve the study of mesoscopic networks
composed of a few tens of neurons. Nonetheless, mathematical methods that
correctly describe networks of small size are still rare, and this prevents us to
make progress in understanding neural dynamics at these intermediate scales. Here
we develop a novel systematic analysis of the dynamics of arbitrarily small
networks composed of homogeneous populations of excitatory and inhibitory firing
rate neurons. We study the local bifurcations of their neural activity with an
approach that is largely analytically tractable, and we numerically determine the
global bifurcations. We find that for strong inhibition these networks give rise
to very complex dynamics, caused by the formation of multiple branching solutions
of the neural dynamics equations that emerge through spontaneous symmetry
breaking. This qualitative change of the neural dynamics is a finite-size effect
of the network, that reveals qualitative and previously unexplored differences
between mesoscopic cortical circuits and their mean-field approximation. The most
important consequence of spontaneous symmetry-breaking is the ability of
mesoscopic networks to regulate their degree of functional heterogeneity, which
is thought to help reducing the detrimental effect of noise correlations on
cortical information processing.
PMID- 27494738
TI - New insights into Legionella pneumophila biofilm regulation by c-di-GMP
signaling.
AB - The waterborne pathogen Legionella pneumophila grows as a biofilm, freely or
inside amoebae. Cyclic-di-GMP (c-di-GMP), a bacterial second messenger frequently
implicated in biofilm formation, is synthesized and degraded by diguanylate
cyclases (DGCs) and phosphodiesterases (PDEs), respectively. To characterize the
c-di-GMP-metabolizing enzymes involved in L. pneumophila biofilm regulation, the
consequences on biofilm formation and the c-di-GMP concentration of each
corresponding gene inactivation were assessed in the Lens strain. The results
showed that one DGC and two PDEs enhance different aspects of biofilm formation,
while two proteins with dual activity (DGC/PDE) inhibit biofilm growth.
Surprisingly, only two mutants exhibited a change in global c-di-GMP
concentration. This study highlights that specific c-di-GMP pathways control L.
pneumophila biofilm formation, most likely via temporary and/or local modulation
of c-di-GMP concentration. Furthermore, Lpl1054 DGC is required to enable the
formation a dense biofilm in response to nitric oxide, a signal for biofilm
dispersion in many other species.
PMID- 27494739
TI - The Prosocial Cyberball Game: Compensating for social exclusion and its
associations with empathic concern and bullying in adolescents.
AB - In this study we examined prosocial compensating behavior towards socially
excluded ingroup and outgroup members by using a 'Prosocial Cyberball Game' in 9
17 year old Dutch adolescents (N = 133). Results showed that adolescents
compensated for the social exclusion of an unknown peer in a virtual ball tossing
game, by tossing the ball more often to that player in compensation conditions
compared to the fair play condition. The proportion of tosses towards the
excluded player did not significantly differ as a function of the group status of
that player. Although compensating behavior towards ingroup versus outgroup
members did not differ, the underlying motivation for this behavior may vary.
More empathic concern was associated with more prosocial tosses towards an
ingroup member, while more self-reported bullying behavior was associated with
less compensating behavior in the outgroup condition. These findings may have
practical implications for programs intending to change bystander behavior in
bullying situations.
PMID- 27494740
TI - The effectiveness of the Penn Resiliency Programme (PRP) and its adapted versions
in reducing depression and anxiety and improving explanatory style: A systematic
review and meta-analysis.
AB - Mental health problems in children can be precursors of psychosocial problems in
adulthood. The aim of this study is to assess the effectiveness of the universal
application of a resilience intervention (PRP and derivatives), which has been
proposed for large scale roll-out. Electronic databases were searched for
published randomized controlled trials of PRP and derivatives to prevent
depression and anxiety and improve explanatory style in students aged 8-17 years.
Studies were meta-analysed and effect sizes with confidence intervals were
calculated. The Quality Assessment Tool for Quantitative Studies of the Effective
Public Health Practice Project was used to determine the confidence in the effect
estimates. Nine trials from Australia, the Netherlands and USA met the inclusion
criteria. No evidence of PRP in reducing depression or anxiety and improving
explanatory style was found. The large scale roll-out of PRP cannot be
recommended. The content and structure of universal PRP should be re-considered.
PMID- 27494741
TI - Adolescent harm avoidance as a longitudinal predictor of maladaptive cognitive
emotion regulation in adulthood: The mediating role of inhibitory control.
AB - The current study investigates the effect of adolescent harm avoidance (HA) on
maladaptive cognitive emotion regulation strategies (mCER) in early adulthood.
The mediating role of inhibitory control and the moderating effect of gender on
this link were also examined. Longitudinal data from 261 adolescents (147 female)
were collected in three phases (T0, T1 and T2) over approximately 10 years.
Results revealed that, after controlling for HA in adulthood (T2), female
adolescents' HA (T0) significantly predicted mCER strategies after 10 years (T2),
whereas male adolescents' HA only predicted catastrophizing. In addition,
attentional impulsivity (T1) significantly mediated the relation between HA and
mCER, though only among women. There was no significant indirect effect for
emotional interference and stop-signal reaction time. Results revealed gender and
measure specific associations between HA and inhibitory control and suggest that
HA could induce inhibitory deficits leading to mCER.
PMID- 27494742
TI - microRNA-214 Governs Lung Cancer Growth and Metastasis by Targeting
Carboxypeptidase-D.
AB - Lung cancer is one of the most malignant cancers with a high metastatic
potential. The purpose of this study was to study the role and the underlying
mechanism of miR-214 in lung cancer progression. The expression of miR-214 in
normal lung and lung cancer tissue was analyzed by quantitative real-time PCR
analysis. Furthermore, H1299 cells were infected with miR-214 lentivirus, and the
effect of infection on cell viability and migration was analyzed.
Carboxypeptidase-D (CPD), as a potential target of miR-214, was characterized in
either normal lung or lung cancer tissues. The interaction of CPD expression with
the tumor suppressing effect of miR-214 was characterized. We demonstrated that
low miR-214 expression is a hallmark of lung cancer, especially high-grade and
metastatic cancer. In vitro studies in H1299 cells confirmed that low miR-214
expression is associated with enhanced proliferation and migratory abilities.
Similarly, CPD overexpression coincides with high-grade lung cancer and the CPD
overexpression could reverse the inhibitory effects of miR-214. miR-214 is a
tumor suppressor in lung cancer. miR-214 inhibits lung cancer progression by
targeting CPD. The miR-214-CPD axis may be a therapeutic axis for lung cancer
patients.
PMID- 27494744
TI - Systematics of BX3 and BX2(+) Complexes (X = F, Cl, Br, I) with Neutral
Diphosphine and Diarsine Ligands.
AB - The coordination chemistry of the neutral diphosphines, R2P(CH2)2PR2 (R = Me or
Et) and o-C6H4(PR'2)2 (R' = Me or Ph), and the diarsine, o-C6H4(AsMe2)2, toward
the Lewis acidic BX3 (X = F, Cl, Br, and I) fragments is reported, including
several rare complexes incorporating BF3 and BF2(+). The studies have revealed
that the flexible dimethylene linked diphosphines form [(BX3)2{MU-R2P(CH2)2PR2}]
exclusively, confirmed by multinuclear NMR ((1)H, (11)B, (19)F{(1)H}, and
(31)P{(1)H}) and IR spectroscopy and microanalytical data. Crystallographic
determinations of the four BX3 complexes with Et2P(CH2)2PEt2 confirm the 2:1
stoichiometry and, taken together with the spectroscopic data, reveal that the
Lewis acid behavior of the BX3 fragment toward phosphine ligands increases in the
order F ? Cl ~ Br < I. The first diphosphine- and diarsine-coordinated
dihaloboronium cations, [BX2{o-C6H4(EMe2)2}](+) (E = P, As), are obtained using
the rigid, preorganized o-phenylene linkages. These complexes are characterized
similarly, and the data indicate that the complexes with o-C6H4(AsMe2)2 are much
more labile and readily decomposed than the phosphine analogues. X-ray
crystallographic studies on [BX2{o-C6H4(PMe2)2}][BX4] (X = Cl, Br), [BI2{o
C6H4(PMe2)2}][I3], and [BCl2{o-C6H4(AsMe2)2}][BCl4] confirm the presence of
distorted tetrahedral coordination at boron through a chelating diphosphine or
diarsine and two X ligands, with d(B-P) revealing a similar increase in Lewis
acidity down group 17. Comparison of d(B-P) and d(B-As) reveals an increase of
ca. 0.08 A from P to As. Reaction of BCl3 with the diphosphine dioxide
Ph2P(O)CH2P(O)Ph2 gives the ligand-bridged dimer [(BCl3)2{Ph2P(O)CH2P(O)Ph2}],
while using either BF3 gas or [BF3(SMe2)] gives a mixture containing both
[(BF3)2{MU-Ph2P(O)CH2P(O)Ph2}] and the unexpected difluoroboronium salt,
[BF2{Ph2P(O)CH2P(O)Ph2}][B2F7] containing a chelating phosphine oxide. The
structure of the latter was confirmed crystallographically.
PMID- 27494743
TI - Soda consumption and hospital admissions among Californian adults with asthma.
AB - INTRODUCTION: Asthma prevalence has been increasing consistently since 1995 in
California. Recent studies have found that consuming soda and sugar-containing
drinks may pose a risk for asthma. Research that examines the relationship
between soda intake and asthma among adult asthmatics is limited. OBJECTIVE: This
study investigated the relationship between sugar-sweetened soda consumption and
asthma hospitalization among adult asthmatics in California. METHODS: This cross
sectional study was based on the 2011-2012 California Health Interview Survey
(CHIS) data and included 3,784 adults who were diagnosed with asthma by a doctor
and who currently reported either that they still had asthma, or that they had
suffered from an asthma attack in the last 12 months. The analysis was survey
weighted. The exposure variable was soda intake measured as the number of times
soda was consumed in the last week. The health outcome measure was overnight
hospital admission due to asthma. Logistic regression was used to examine the
association between soda consumption and overnight hospital admission after
adjusting for age, education, sex, race/ethnicity, weight status, smoking status,
and self-rated health. RESULTS: Adults with asthma who drank soda three or more
times per week reported higher odds of overnight hospitalization (adjusted odds
ratio = 2.77, 95% CI: 1.51-5.10, p = 0.001). CONCLUSIONS: Our findings suggest
that efforts designed to limit soda consumption would benefit asthma suffers by
reducing hospital admissions. This, however, needs further research to confirm a
direct causal association.
PMID- 27494745
TI - Separation of phenol-containing pyrolysis products using comprehensive two
dimensional chromatography with columns based on pyridinium ionic liquids.
AB - We describe the application of columns with highly polar stationary liquid phases
based on pyridinium ionic liquids for the two-dimensional chromatography
separation of bio-oil and product of coal pyrolysis. By using inverse combination
columns-a first ionic liquid column and a second nonpolar column-good separation
results have been obtained. In the analysis of coal pyrolysis products, the
suggested approach provides a much better resolution between components in
comparison with a less polar first-dimension column (based on polyethylene
glycol). A good selectivity for the peaks of phenols is observed, and the group
of phenols is well detached and separated from the group of diaromatics. A good
separation picture was obtained also for bio-oil, the groups of phenols and
guaiacol derivatives are distinguished with good resolution of substances within
each group.
PMID- 27494746
TI - Access to experimentally infeasible spectra by pure-shift NMR covariance.
AB - Covariance processing is a versatile processing tool to generate synthetic NMR
spectral representations without the need to acquire time-consuming experimental
datasets. Here we show that even experimentally prohibited NMR spectra can be
reconstructed by introducing key features of a reference 1D CHn-edited spectrum
into standard 2D spectra. This general procedure is illustrated with the
calculation of experimentally infeasible multiplicity-edited pure-shift NMR
spectra of some very popular homonuclear (ME-psCOSY and ME-psTOCSY) and
heteronuclear (ME-psHSQC-TOCSY and ME-psHMBC) experiments.
PMID- 27494747
TI - Different blood pressure responses to opioids in 3 rat hypertension models: role
of the baseline status of sympathetic and renin-angiotensin systems.
AB - Opioids interact with sympathetic and renin-angiotensin systems in control of
mean arterial pressure (MAP). Our earlier finding that biphalin, a synthetic
enkephalin analogue, decreased MAP in anaesthetized spontaneously hypertensive
rats (SHR) prompted us to further explore this action, to get new insights into
pathogenesis of various forms of hypertension. Biphalin effects were studied in
SHR, uninephrectomized rats on a high-salt diet (HS/UNX), and rats with
angiotensin-induced hypertension (Ang-iH). Besides MAP, renal and iliac blood
flows (RBF, IBF) and vascular resistances were measured. In anaesthetized and
conscious SHR, biphalin (300 MUg.h-1.kg-1 i.v.) decreased MAP by ~10 and ~20 mm
Hg, respectively (P < 0.001). In anaesthetized HS/UNX and normotensive rats, MAP
increased by ~6-7 mm Hg (P < 0.02); without anaesthesia, only transient decreases
occurred. MAP never changed in Ang-iH rats. Morphine (1.5 mg.h-1.kg-1 i.v.)
decreased MAP in HS/UNX but only transiently so without anaesthesia; such
anaesthesia dependence of response was also seen in normotensive rats. Ang-iH
rats never responded to morphine. Hypotensive effect in SHR only depends
primarily on the reduction by biphalin of vascular responsiveness to increased
sympathetic stimulation; such increase is well documented for SHR. No MAP
response to biphalin or morphine in Ang-iH could depend on angiotensin-induced
alterations of the vascular wall morphology and function.
PMID- 27494748
TI - Invited Commentary.
PMID- 27494749
TI - Surgical Approaches to Non-thyrogenic and Non-thymic Mediastinal Tumors of the
Thoracic Inlet.
AB - BACKGROUND: Non-thyrogenic and non-thymic mediastinal tumors of the thoracic
inlet are in close proximity to several important vessels and nerves. The narrow
confines of the thoracic inlet make complete excision of these tumors difficult,
and selecting the appropriate surgical approach is important to successful
resection. METHODS: Records from 57 patients who presented to our department with
non-thyrogenic and non-thymogenic tumors of the thoracic inlet from November 2004
to November 2015 were reviewed. All but one of the patients received surgical
treatment. Thirty-two tumors were excised via video-assisted thoracic surgery
(VATS). Other approaches included thoracotomy, supraclavicular incision,
supraclavicular incision plus thoracotomy/VATS, and a posterior midline approach
with semi-laminectomy combined with VATS. RESULTS: Tumors were resected
completely in 54 cases and partially in one. One procedure (VATS) was aborted.
There were no surgical mortalities, but there were some postoperative
complications. The majority of the tumors were benign neurogenic tumors.
CONCLUSIONS: Most tumors of the thoracic inlet are benign and can be removed via
VATS. Thoracotomy is the appropriate approach for large tumors, particularly in
cases where the first to second rib cannot be visualized. A supraclavicular
approach is recommended for resection of tumors arising from the brachial plexus,
and a supraclavicular approach combined with VATS or thoracotomy may be useful
for larger masses. A posterior midline approach with semi-laminectomy combined
with VATS is appropriate for dumbbell-shaped tumors.
PMID- 27494750
TI - Expanding Surgical Opportunities: Endoscopic Harvesting of the Vena Saphena Parva
in Supine Position.
AB - The small saphenous vein (SSV) has proved to be a valid graft option for coronary
artery bypass grafting (CABG), if other grafts are absent or unsuitable. Beside
the described open technique we herein present our approach to endoscopic
harvesting in supine position in seven patients. Harvesting was successful in six
patients. Mean skin-to-skin time was 29.8 minutes. There were no infections or
neurological deficits and the intraoperatively measured graft flow was excellent
according to mean flow and low pulsatility index. Therefore, endoscopic
harvesting of the SSV extends surgical opportunities not only in CABG, but also
in surgery of peripheral artery disease.
PMID- 27494751
TI - Clinical use of ruxolitinib in an academic medical center in unselected patients
with myeloproliferative neoplasms not on clinical study.
AB - Ruxolitinib is the only approved therapy for myelofibrosis (MF). However, its use
in patients with myeloproliferative neoplasms (MPN) not participating in clinical
studies has been poorly described. We reviewed the medical records of 45 patients
(35 MF, 10 others) treated with ruxolitinib at our center, off clinical study,
during the year after its approval. Patients had advanced features and were
refractory to multiple therapies. Ruxolitinib was effective in reducing
splenomegaly (51% response rate) and constitutional symptoms (42% response rate).
It controlled blood counts in patients with polycythemia and thrombocythemia but
was not effective in patients with non-classic MPNs. Ruxolitinib was an active
therapy in patients previously treated with a JAK inhibitor and was safely
combined with hypomethylating agents in patients with elevated blasts. Median
overall survival was 24 months; 10 patients transformed to acute leukemia. Its
use in combination with other active agents should be further explored in
clinical studies.
PMID- 27494752
TI - Synthesis of a novel PEGDGA-coated hPAMAM complex as an efficient and
biocompatible gene delivery vector: an in vitro and in vivo study.
AB - hPAMAM/DNA polyplexes, compared to viral vectors, display unique characteristics
including more safety, less immune response outcomes, a simpler synthesis and an
easier process. Given the importance of these polymers, hPAMAM coated with the
PEGDGA copolymer was developed as a promising non-viral gene carrier. In the
present study, a new complex of hPAMAM, PEGDGA-modified hyperbranched
polyamidoamine (hPAMAM), was established as a versatile non-viral gene vector.
The hPAMAM polymer was synthesized by using a modified one-pot method. The
resulting hPAMAM-PEGDGA polymer was able to efficiently protect encapsulated-DNA
against degradation for over 2 h. In addition to low cytotoxicity, the
transfection efficiency of hPAMAM-PEGDGA represented much higher (p < 0.05) than
that of Lipofectamine 2000 in both MCF7 and MDA-MB231 cells (an approximately 4.5
fold increase). Cellular uptake of hPAMAM-PEGDGA in MDA-MB231 cells, 254.79 +/-
2.1, was significantly higher than that in MCF7 cells, 51.61 +/- 6.1 (p < 0.05).
EMA-labeled DNA can be clearly observed in the tumor tissue of mice receiving
hPAMAM-PEGDGA/EMA-labeled DNA. However, a significant number of fluorescent spots
can be found in the tumor tissue of mice receiving hPAMAM/DNA, when compared to
those treated with naked hPAMAM/DNA. It has been observed that GFP is expressed
more highly in hPAMAM-PEGDGA/EMA-labeled/DNA than the one in PAMAM/DNA. The
results indicated that hPAMAM-PEGDGA-mediated gene delivery to breast cancer
cells is a feasible and effective strategy that may offer a new therapeutic
avenue as a non-viral gene delivery carrier. Notably, According to these
findings, this newly-introduced copolymer, the hPAMAM-PEGDGA complex, has proved
to be a promising strategy for drug or gene delivery to tissues or cell types of
interest, particularly to triple-negative breast cancer.
PMID- 27494753
TI - Trans Bodies, Trans Selves: The Owner's Manual to Life, Health, and Self.
AB - In this article, the author reviews Trans Bodies, Trans Selves as an educational
and clinical resource from the perspective of an academic physician working with
transgender and gender non-conforming patients.
PMID- 27494754
TI - Chrysobalanus icaco L. fruits inhibit NADPH oxidase complex and protect DNA
against doxorubicin-induced damage in Wistar male rats.
AB - Chrysobalanus icaco L. is an underexplored plant found in tropical areas around
the globe. Currently, there is no apparent information regarding the effects C.
icaco fruits may exert in vivo or potential role in health promotion. This study
aimed at providing evidence regarding the in vivo influence of this fruit on
antigenotoxicity, antimutagenicity, and oxidative stress in rats. Male Wistar
rats were treated with 100, 200, or 400 mg/kg body weight (bw)/d C. icaco fruit
for 14 d. Doxorubicin (DXR, 15 mg/kg bw, ip) was used for DNA damaging and as an
oxidant to generate reactive oxygen species (ROS). Genomic instability was
assessed by the comet assay and micronucleus (MN) test, while antioxidant
activity was determined by oxidative burst of neutrophils. Chrysobalanus icaco
fruit polyphenols were quantified and characterized by high-performance liquid
chromatography coupled to a diode array detector and tandem mass spectrometer
(HPLC-DAD-MS/MS). The concentrations of 19 chemical elements were determined by
inductively coupled plasma-mass spectroscopy (ICP-MS). Significant amounts of
polyphenols, magnesium, and selenium were found in C. icaco fruit. This fruit
displayed in vivo antioxidant activity against DXR-induced damage in rat
peripheral blood neutrophils, antigenotoxicity in peripheral blood cells, and
antimutagenicity in bone-marrow cells and peripheral blood cells. Correlation
analyses between endpoints examined indicated that the mechanism underlying
chemopreventive actions of C. icaco fruit was attributed to inhibition of NADPH
oxidase complex manifested as low levels of DNA damage in animals exposed to DXR.
Data indicate that phytochemicals and minerals in C. icaco fruit protect DNA
against damage in vivo associated with their antioxidant properties.
PMID- 27494755
TI - Size matters: decreased glandular levels of anti-inflammatory short thymic
stromal lymphopoietin in primary Sjogren's syndrome.
PMID- 27494756
TI - Neurobehavioural assessment and diagnosis in disorders of consciousness: a
preliminary study of the Sensory Tool to Assess Responsiveness (STAR).
AB - The Sensory Tool to Assess Responsiveness (STAR) is an interdisciplinary
neurobehavioural diagnostic tool for individuals with prolonged disorders of
consciousness. It utilises current diagnostic criteria and is intended to improve
upon the high misdiagnosis rate in this population. This study assesses the inter
rater reliability of the STAR and its diagnostic validity in comparison with the
Coma Recovery Scale-Revised (CRS-R) and the Wessex Head Injury Matrix (WHIM).
Participants were patients with severe acquired brain injury resulting in a
disorder of consciousness, who were admitted to the Royal Leamington Spa
Rehabilitation Hospital between 1999 and 2009. Patients underwent sensory
stimulation sessions during their period of admission, which were recorded on
video. Using this footage, patients were re-assessed for this study using the
STAR, WHIM and CRS-R criteria. The STAR demonstrated "moderate" inter-rater
reliability, "substantial" diagnostic agreement with the CRS-R, and "moderate"
agreement with the WHIM. There were no significant differences between diagnoses
assigned by the different assessments. The STAR demonstrated a good degree of
inter-rater reliability in identification of diagnoses for patients with
disorders of consciousness. The diagnostic outcomes of the STAR agreed at a good
level with the CRS-R, moderately with the WHIM, and did not significantly differ
from either. This demonstrates the reliability and validity of the STAR, showing
its appropriateness for clinical use. Future longitudinal studies and research
into the STAR's applicability in long-stay rehabilitation are indicated.
PMID- 27494757
TI - Characteristics, Properties and Analytical Methods of Cefadroxil: A Review.
AB - Infections are the second leading cause of mortality worldwide and there are many
reasons justifying the need for further studies of antimicrobial agents.
Cefadroxil is a drug that has bactericidal activity and broad spectrum of action.
Quantitative analyzes about cefadroxil are essential for the understanding of
bioavailability, bioequivalence, and therapeutic control, which will ensure the
product's characteristics and patients' safety. Thus, this study highlights a
brief literature review about the drug and the existing methods developed for the
determination of cefadroxil found in official and scientific papers. According to
the methods found in literature, liquid chromatography and spectrophotometry of
absorption in the ultraviolet region prevailed over the others. Importantly, most
of the solvents used for the development of the described analytical methods are
toxic to the environment, making it necessary to educate researchers and
pharmaceutical companies to use nontoxic solvents to provide environmental
friendly methods and better benefits to equipments and mainly to analysts.
PMID- 27494758
TI - Predictors of future exacerbation risk in patients with asthma.
AB - OBJECTIVES: Although modern treatment of asthma improves asthma control, some
patients still experience exacerbations. The aim of the present study was to
detect predictors of asthmatic exacerbations Methods: We included patients with
asthma followed up in asthma clinics of 2 tertiary University hospitals.
Demographic and functional characteristics, levels of exhaled NO, and
inflammatory biomarkers (IL-13, EpsilonCP kappaalphaiota IL-8) and cell counts in
induced sputum were recorded at baseline. Measurements were performed with the
patients in stability and were considered as their personal best. Patients
received optimal treatment with good compliance and were followed up for 1 year
for asthma exacerbations occurrence. Evaluation of the effect of recorded
parameters on asthma exacerbations was performed with univariate and multivariate
Poisson regression analysis. RESULTS: 171 patients (118 female) with bronchial
asthma (mean age 51.6 +/- 13.2 years) were included in the study. The mean number
of exacerbations in 1 year of follow up was 0.4 +/- 0.8 while the majority of
patients (71.9%) did not experience any exacerbation. In multivariate Poisson
Regression analysis only 3 characteristics were predictors of future
exacerbations: FEV1 [IRR(95% CI)], [0.970(0.954-0.987)], p = 0.001, high BMI
[1.078(1.030-1.129)], p = 0.001, and the need for permanent treatment with oral
corticosteroids for asthma control maintenance [2.542(1.083-5.964)], p = 0.032
CONCLUSION: Optimal guideline-based asthma management results in minimal
occurrence of exacerbations in the majority of patients. Predictors of
exacerbations are low FEV1 levels in stability, high BMI and the need for
permanent treatment with oral corticosteroids.
PMID- 27494759
TI - Photocatalytic Generation of 2-Azolyl Radicals: Intermediates for the Azolylation
of Arenes and Heteroarenes via C-H Functionalization.
AB - The 2-azolyl radical, generated from 2-bromoazoles via photocatalysis, is a
powerful intermediate for the intermolecular arylation of unmodified
(hetero)arenes. The reaction is characterized by mild conditions, operational
simplicity, tolerance toward functional and sterically demanding groups, broad
scope, and anti-Minisci selectivity. A working mechanism is provided, and a low
solubility amine is essential for successful coupling. The utility of the
reaction is demonstrated via late-stage functionalization of methyl estrone and
application toward other bromoarenes.
PMID- 27494760
TI - Single-Molecule Analysis of the Supramolecular Organization of the M2 Muscarinic
Receptor and the Galphai1 Protein.
AB - G protein-coupled receptors constitute the largest family of transmembrane
signaling proteins and the largest pool of drug targets, yet their mechanism of
action remains obscure. That uncertainty relates to unresolved questions
regarding the supramolecular nature of the signaling complex formed by receptor
and G protein. We therefore have characterized the oligomeric status of eGFP
tagged M2 muscarinic receptor (M2R) and Gi1 by single-particle photobleaching of
immobilized complexes. The method was calibrated with multiplexed controls
comprising 1-4 copies of fused eGFP. The photobleaching patterns of eGFP-M2R were
indicative of a tetramer and unaffected by muscarinic ligands; those of eGFP-Gi1
were indicative of a hexamer and unaffected by GTPgammaS. A complex of M2R and
Gi1 was tetrameric in both, and activation by a full agonist plus GTPgammaS
reduced the oligomeric size of Gi1 without affecting that of the receptor. A
similar reduction was observed upon activation of eGFP-Galphai1 by the receptor
mimic mastoparan plus GTPgammaS, and constitutively active eGFP-Galphai1 was
predominantly dimeric. The oligomeric nature of Gi1 in live CHO cells was
demonstrated by means of Forster resonance energy transfer and dual-color
fluorescence correlation spectroscopy in studies with eGFP- and mCherry-labeled
Galphai1; stochastic FRET was ruled out by means of non-interacting pairs. These
results suggest that the complex between M2R and holo-Gi1 is an octamer
comprising four copies of each, and that activation is accompanied by a decrease
in the oligomeric size of Gi1. The structural feasibility of such a complex was
demonstrated in molecular dynamics simulations.
PMID- 27494761
TI - Cu2ZnSnS4 Nanoparticle Sensitized Metal-Organic Framework Derived Mesoporous TiO2
as Photoanodes for High-Performance Dye-Sensitized Solar Cells.
AB - We present a facile hot injection and hydrothermal method to synthesize Cu2ZnSnS4
(CZTS) nanoparticles sensitized metal-organic frameworks (MOFs)-derived
mesoporous TiO2. The MOFs-derived TiO2 inherits the large specific surface area
and abundantly porous structures of the MOFs structure, which is of great benefit
to effectively enhance the dye loading capacity, prolong the incident light
traveling length by enhancing the multiple interparticle light-scattering
process, and therefore improve the light absorption capacity. The sensitization
of CZTS nanoparticles effectively enlarges the photoresponse range of TiO2 to the
visible light region and facilitates photoinduced carrier transport. The formed
heterostructure between CZTS nanoparticles and MOFs-derived TiO2 with matched
band gap structure effectively suppresses the recombination rates of
photogenerated electron/hole pairs and prolongs the lifespan of the carriers.
Photoanodes based upon CZTS/MOFs-derived TiO2 photoanodes can achieve the maximal
photocurrent of 17.27 mA cm(-2) and photoelectric conversion performance of
8.10%, nearly 1.93 and 2.21 times higher than those of TiO2-based photoanode. The
related mechanism and model are investigated. The strikingly improved
photoelectric properties are ascribed to a synergistic action between the MOFs
derived TiO2 and the sensitization of CZTS nanoparticles.
PMID- 27494762
TI - The Structure of Multidimensional Perfectionism: Support for a Bifactor Model
With a Dominant General Factor.
AB - Evidence suggests perfectionism is a multidimensional construct composed of 2
higher order factors: perfectionistic strivings and perfectionistic concerns.
However, the substantial overlap between perfectionistic strivings and
perfectionistic concerns is problematic, as are the unanswered questions
regarding the structure of perfectionism following removal of common variance.
This research addressed this through bifactor modeling. Three student samples (N
= 742) completed Hewitt and Flett's ( 1991 ) Multidimensional Perfectionism
Scale, Frost, Marten, Lahart, and Rosenblate's ( 1990 ) Multidimensional
Perfectionism Scale, and Slaney, Rice, Mobley, Trippi, and Ashby's ( 2001 )
Almost Perfect Scale-Revised. Greater support was consistently found for the
bifactor model, relative to the 2-factor model. Results suggest the bifactor
model best represents the structure of perfectionism and provide preliminary
support for the use of a general factor score. Researchers are cautioned that
removal of general variance may render the reliability of specific factors (i.e.,
perfectionistic strivings and perfectionistic concerns) suspect.
PMID- 27494764
TI - The Effects of Air Flow Rates, Secondary Air Inlet Geometry, Fuel Type, and
Operating Mode on the Performance of Gasifier Cookstoves.
AB - Development of biomass cookstoves that reduce emissions of CO and PM2.5 by more
than 50% and 95%, respectively, compared to a three-stone fire has been promoted
as part of efforts to reduce exposure to household air pollution (HAP) among
people that cook with solid fuels. Gasifier cookstoves have attracted interest
because some have been shown to emit less CO and PM2.5 than other designs. A
laboratory test bed and new test procedure were used to investigate the influence
of air flow rates, stove geometry, fuel type, and operating mode on gasifier
cookstove performance. Power output, CO emissions, PM2.5 emissions, fuel
consumption rates, producer gas composition, and fuel bed temperatures were
measured. The test bed emitted <41 mg.MJd-1 PM2.5 and <8 g.MJd-1 CO when
operating normally with certain prepared fuels, but order of magnitude increases
in emission factors were observed for other fuels and during refueling. Changes
in operating mode and fuel type also affected the composition of the producer gas
entering the secondary combustion zone. Overall, the results suggest that the
effects of fuel type and operator behavior on emissions need to be considered, in
addition to cookstove design, as part of efforts to reduce exposure to HAP.
PMID- 27494763
TI - Structure Prediction of RNA Loops with a Probabilistic Approach.
AB - The knowledge of the tertiary structure of RNA loops is important for
understanding their functions. In this work we develop an efficient approach
named RNApps, specifically designed for predicting the tertiary structure of RNA
loops, including hairpin loops, internal loops, and multi-way junction loops. It
includes a probabilistic coarse-grained RNA model, an all-atom statistical energy
function, a sequential Monte Carlo growth algorithm, and a simulated annealing
procedure. The approach is tested with a dataset including nine RNA loops, a 23S
ribosomal RNA, and a large dataset containing 876 RNAs. The performance is
evaluated and compared with a homology modeling based predictor and an ab initio
predictor. It is found that RNApps has comparable performance with the former one
and outdoes the latter in terms of structure predictions. The approach holds
great promise for accurate and efficient RNA tertiary structure prediction.
PMID- 27494765
TI - Statistical thermodynamics of non-stoichiometric ceria and ceria zirconia solid
solutions.
AB - The thermodynamic redox properties of ceria and ceria zirconia solid solutions
are analysed with a new methodology for modelling such systems based on the
statistical mechanics of lattice configurations. Experimental thermogravimetric
equilibrium data obtained for small non-stoichiometry measurements are combined
with literature data to cover a large range of non-stoichiometry (CeO2-delta,
delta = 0.001-0.32), temperature (1073-1773 K) and oxygen partial pressure (1-10(
13) bar). A dilute species model of defect clusters , obeying the law of mass
action, was sufficient to describe the system over the whole range of conditions,
leading to a simple analytical equation of state for the system. This offers new
physical insight into the redox properties of ceria based materials, and the
theoretical methods developed should also be of great interest for other
materials which exhibit continuous oxygen non-stoichiometry similar to ceria,
such as perovskite oxides.
PMID- 27494766
TI - The attention-weighted sample-size model of visual short-term memory: Attention
capture predicts resource allocation and memory load.
AB - We investigated the capacity of visual short-term memory (VSTM) in a phase
discrimination task that required judgments about the configural relations
between pairs of black and white features. Sewell et al. (2014) previously showed
that VSTM capacity in an orientation discrimination task was well described by a
sample-size model, which views VSTM as a resource comprised of a finite number of
noisy stimulus samples. The model predicts the invariance of [Formula: see text]
, the sum of squared sensitivities across items, for displays of different sizes.
For phase discrimination, the set-size effect significantly exceeded that
predicted by the sample-size model for both simultaneously and sequentially
presented stimuli. Instead, the set-size effect and the serial position curves
with sequential presentation were predicted by an attention-weighted version of
the sample-size model, which assumes that one of the items in the display
captures attention and receives a disproportionate share of resources. The choice
probabilities and response time distributions from the task were well described
by a diffusion decision model in which the drift rates embodied the assumptions
of the attention-weighted sample-size model.
PMID- 27494768
TI - Online Extraction Coupled to Liquid Chromatography Analysis (OLE-LC): Eliminating
Traditional Sample Preparation Steps in the Investigation of Solid Complex
Matrices.
AB - Current methods employed for the analysis of the chemical composition of solid
matrices (such as plant, animal, or human tissues; soil; etc.) often require many
sample treatment steps, including an extraction step with exclusively dedicated
solvents. This work describes an optimized analytical setup in which the
extraction of a solid sample is directly coupled to its analysis by high
performance liquid chromatography. This approach avoids (i) the use of pumps and
valves other than those comprising the HPLC instrument, (ii) the use of solvents
other than those of the mobile phase, and (iii) the need to stop the mobile phase
flow at any time during the full analytical procedure. The compatibility of this
approach with the direct analysis of fresh tissues (leaves, stems, and seeds of
four plant species with dissimilar chemical compositions) was successfully
demonstrated, leading to the elimination of sample preparation steps such as
drying, grinding, concentration, dilution, and filtration, among others. This
work describes a new, simple, and efficient green approach to minimize or
eliminate sample treatment procedures. It could be easily applied for quality
control of plant materials and their derived products through chromatographic
fingerprints and for untargeted metabolomic investigations of solid matrices,
among other applications.
PMID- 27494767
TI - Impact of fibroblast growth factor 21 on the secretome of human perivascular
preadipocytes and adipocytes: a targeted proteomics approach.
AB - CONTEXT: Perivascular adipose tissue (PVAT) is suggested to impact on vascular
cells via humoral factors, possibly contributing to endothelial dysfunction and
atherosclerosis. OBJECTIVE: To address whether the hepatokine fibroblast growth
factor (FGF) 21 affects the PVAT secretome. METHODS: Human perivascular
(pre)adipocytes were subjected to targeted proteomics and whole-genome gene
expression analysis. RESULTS: Preadipocytes, as compared to adipocytes, secreted
higher amounts of inflammatory cytokines and chemokines. Adipocytes released
higher amounts of adipokines [e.g. adipisin, visfatin, dipeptidyl peptidase 4
(DPP4), leptin; p < 0.05, all]. In preadipocytes, omentin 1 release was 1.28-fold
increased by FGF-21 (p < 0.05). In adipocytes, FGF-21 reduced chemerin release by
5% and enhanced DPP4 release by 1.15-fold (p < 0.05, both). FGF-21 altered the
expression of four secretory genes in preadipocytes and of 18 in adipocytes (p <
0.01, all). CONCLUSION: The hepatokine FGF-21 exerts secretome-modulating effects
in human perivascular (pre)adipocytes establishing a new liver-PVAT-blood vessel
axis that possibly contributes to vascular inflammation and atherosclerosis.
PMID- 27494769
TI - Cylindrospermopsin effects on protein profile of HepG2 cells.
AB - Human hepatoma cells (HepG2) were exposed to purified cylindrospermopsin (CYN), a
potent toxicant for eukaryotic cells produced by several cyanobacteria. Exposure
to 10 MUg l-1 of CYN for 24 h resulted in alteration of expression of 48
proteins, from which 26 were identified through mass spectrometry. Exposure to
100 MUg l-1 of CYN for 24 h affected nuclear area and actin filaments intensity,
which can be associated with cell proliferation and toxicity. The proteins are
implicated in different biological processes: protein folding, xenobiotic efflux,
antioxidant defense, energy metabolism and cell anabolism, cell signaling,
tumorigenic potential, and cytoskeleton structure. Protein profile indicates that
CYN exposure may lead to alteration of glucose metabolism that can be associated
with the supply of useful energy to cells respond to chemical stress and
proliferate. Increase of G protein-coupled receptors (GPCRs), heterogeneous
nuclear ribonucleoproteins (hnRNP), and reactive oxygen species (ROS) levels
observed in HepG2 cells can associate with cell proliferation and resistance.
Increase of MRP3 and glutathione peroxidase can protect cells against some
chemicals and ROS. CYN exposure also led to alteration of the expression of
cytoskeleton proteins, which may be associated with cell proliferation and
toxicity.
PMID- 27494770
TI - Electronic cigarette initiation among minority youth in the United States.
AB - BACKGROUND: Electronic cigarettes (e-cigarette) use among youth is a pressing
public health issue, with prevalence of use surpassing that of tobacco
cigarettes. While research concerning e-cigarettes has proliferated in recent
years, there is a dearth of information regarding those whose first exposure to
tobacco products was an e-cigarette. OBJECTIVES: To examine factors associated
with e-cigarette initiation among minority youth in the United States. METHODS:
Data on minority students in middle and high schools in the United States derived
from the 2014 National Youth Tobacco Survey (NYTS) were sampled (weighted N =
27,294,454). We examined e-cigarette initiation among minority youth using
logistic regression models to identify related factors. RESULTS: In 2014, 736,158
minority youth were e-cigarette initiators. Odds of e-cigarette initiation was
highest among Hispanic youth [adjusted odds ratio (AOR) = 2.70; 95% confidence
interval (CI) = 1.60-4.56]. Exposure to e-cigarette advertising (AOR = 1.64; 95%
CI = 1.07-2.50), perceptions of little to no harm (AOR = 7.08; 95% CI = 4.03
12.46), and believing e-cigarettes were less addictive than tobacco (AOR = 2.15;
95% CI = 1.52-3.02) were associated with e-cigarette initiation. CONCLUSIONS:
Odds of initiating e-cigarette use was highest among Hispanic youth. Among
minority youth, e-cigarette initiation was associated with perceptions of harm
and addiction potential, as well as exposure to e-cigarette advertising.
Therefore, prevention efforts targeting minority youth who are at risk of
becoming e-cigarette initiators may benefit by incorporating these factors into
prevention campaigns.
PMID- 27494771
TI - [Staff Satisfaction within Duty Hour Models: Longitudinal Survey on Suitability
and Legal Conformity at a Surgical Maximum Care Department].
AB - Background Between the conflicting requirements of clinic organisation, the
European Working Time Directive, patient safety, an increasing lack of junior
staff, and competitiveness, the development of ideal duty hour models is vital to
ensure maximum quality of care within the legal requirements. To achieve this, it
is useful to evaluate the actual effects of duty hour models on staff
satisfaction. Materials and Methods After the traditional 24-hour duty shift was
given up in a surgical maximum care centre in 2007, an 18-hour duty shift was
implemented, followed by a 12-hour shift in 2008, to improve handovers and reduce
loss of information. The effects on work organisation, quality of life and salary
were analysed in an anonymous survey in 2008. The staff survey was repeated in
2014. Results With a response rate of 95% of questionnaires in 2008 and a 93%
response rate in 2014, the 12-hour duty model received negative ratings due to
its high duty frequency and subsequent social strain. Also the physical strain
and chronic tiredness were rated as most severe in the 12-hour rota. The 18-hour
duty shift was the model of choice amongst staff. The 24-hour duty model was
rated as the best compromise between the requirements of work organisation and
staff satisfaction, and therefore this duty model was adapted accordingly in
2015. Conclusion The essential basis of a surgical department is a duty hour
model suited to the requirements of work organisation, the Working Time Directive
and the needs of the surgical staff. A 12-hour duty model can be ideal for work
organisation, but only if augmented with an adequate number of staff members, the
implementation of this model is possible without the frequency of 12-hour shifts
being too high associated with strain on surgical staff and a perceived
deterioration of quality of life. A staff survey should be performed on a regular
basis to assess the actual effects of duty hour models and enable further
optimisation. The much criticised 24-hour duty model seems to be much better than
its reputation, if augmented by additional staff members in the evening hours.
PMID- 27494772
TI - Chitosan/alginate based multilayers to control drug release from ophthalmic lens.
AB - In this study we investigated the possibility of using layer-by-layer deposition,
based in natural polymers (chitosan and alginate), to control the release of
different ophthalmic drugs from three types of lens materials: a silicone-based
hydrogel recently proposed by our group as drug releasing soft contact lens (SCL)
material and two commercially available materials: CI26Y for intraocular lens
(IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one
double layer of (alginate - CaCl2)/(chitosan+glyoxal) topped with a final
alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved
to have excellent features to control the release of the anti-inflammatory,
diclofenac, while keeping or improving the physical properties of the lenses. The
coating leads to a controlled release of diclofenac from SCL and IOL materials
for, at least, one week. Due to its high hydrophilicity (water contact angle~0)
and biocompatibility, it should avoid the use of further surface treatments to
enhance the users comfort. However, the barrier effect of this coating is
specific for diclofenac, giving evidence to the need of optimizing the chemical
composition of the layers in view of the desired drug.
PMID- 27494773
TI - The tyrosine kinase inhibitor, nilotinib potentiates a prothrombotic state.
AB - Tyrosine kinase inhibitors (TKI) such as imatinib, nilotinib and dasatinib are
now established as highly effective frontline therapies for chronic myeloid
leukaemia (CML). Disease control is achieved in the majority of patients and
survival is excellent such that recent focus has been on toxicities of these
agents. Cumulative data have reported an excess of serious vascular
complications, including arterial thrombosis and peripheral arterial occlusive
disease, in patients receiving nilotinib in comparison with other TKIs, with
resultant interest in delineating the pathophysiology and implications for
rationale cardiovascular risk modification. To address this issue, we studied the
effects of imatinib, nilotinib and dasatinib on platelet function and thrombus
formation in human and mouse models using in vitro, ex vivo and in vivo
approaches. In vitro studies demonstrated that dasatinib and imatinib but not
nilotinib inhibited ADP, CRP, and collagen-induced platelet aggregation and
moreover, that nilotinib potentiated PAR-1-mediated alpha granule release.
Pretreatment of wild-type C57BL/6 mice with nilotinib but not imatinib or
dasatinib, significantly increased thrombus growth and stability, on type I
collagen under ex vivo arterial flow conditions and increased thrombus growth and
stability following FeCl3-induced vascular injury of mesenteric arterioles and
carotid artery injury in vivo. Whole blood from nilotinib-treated CML patients,
demonstrated increased platelet adhesion ex vivo under flow, increased plasma
soluble P- and E-selectin, sICAM-1, sVCAM-1, TNF-alpha, IL-6 levels and
endogenous thrombin potential (ETP) levels in vivo, despite being on daily low
dose aspirin. These results demonstrate that nilotinib can potentiate platelet
and endothelial activation and platelet thrombus formation ex vivo and in vivo.
PMID- 27494774
TI - Cost-of-illness models for venous thromboembolism: One size does not fit all.
PMID- 27494777
TI - Early remission status predicts long-term outcomes in patients with Crohn's
disease treated with certolizumab pegol.
AB - BACKGROUND: In Crohn's disease (CD), rapid response to anti-tumor necrosis factor
therapy improves short- and medium-term outcomes, but the relationship between
early remission (ER) and long-term remission is unclear. AIMS: This exploratory
analysis of PRECiSE 3 (NCT00160524) assessed whether ER after initiation of
certolizumab pegol predicted long-term remission. METHODS: Patients enrolled in
PRECiSE 3 had completed PRECiSE 1 or 2, two randomized placebo-controlled studies
for moderate to severe CD, and received open-label certolizumab pegol 400 mg
every 4 weeks for a total treatment duration of <=7.5 years. Time to loss of
remission between patients with and without ER (Harvey-Bradshaw Index <=4 at or
before Week 6 of PRECiSE 1 or 2) was compared by log-rank test of Kaplan-Meier
estimates. RESULTS: At baseline, patients with (n = 242) and without (n = 148) ER
had mean (standard deviation [SD]) durations of CD of 6.8 (6.6) and 7.4 (7.8)
years, mean (SD) CD Activity Index scores of 280.3 (53.4) and 311.1 (55.5), with
45.5% and 41.9% of patients having ileocolonic CD, and median C-reactive protein
concentrations of 8.0 and 5.0 mg/L, respectively. Median certolizumab pegol
plasma concentrations during the first 6 weeks of therapy were similar in both
groups. Mean time to loss of remission was significantly longer in patients with
versus without ER (2.77 vs. 1.14 years, p < 0.0001). CONCLUSIONS: In certolizumab
pegol-treated patients with CD, ER appears to be an important predictor of long
term clinical remission. Prospective trials are needed to determine whether ER
improves other long-term outcomes.
PMID- 27494776
TI - Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial
clearance through targeting JNK2 in human macrophages.
AB - Induction of cell apoptosis is one of the major host defense mechanisms through
which macrophages control Mycobacterium tuberculosis (Mtb) infection. However,
the mechanisms underlying macrophage apoptosis triggered by Mtb infection are
still largely unknown. In this study, a microarray profiling survey revealed 14
miRNAs were down-regulated in CD14+ monocytes from active pulmonary tuberculosis
patients, and only the reduction of miR-20a-5p could be reversed after successful
anti-tuberculosis treatment. Validation of miR-20a-5p expression was confirmed
using real time qPCR. Moreover, miR-20a-5p expression also decreased in
differentiated THP-1 macrophages after mycobacterial infection in vitro.
Functional assays through forced or inhibited expression of miR-20a-5p in THP-1
macrophages demonstrated that miR-20a-5p functioned as a negative regulator of
mycobacterial-triggered apoptosis. Importantly, inhibition of miR-20a-5p
expression resulted in more efficient mycobacterial clearance from infected THP-1
macrophages while miR-20a-5p overexpression promoted mycobacterial survival.
Mechanistically, miR-20a-5p was demonstrated to regulate Bim expression in a JNK2
dependent manner, unlike Bcl2, and luciferase assay showed JNK2 was a novel
direct target of miR-20a-5p. Together, our findings indicate that downregulation
of miR-20a-5p triggers macrophage apoptosis as a novel mechanism for host defense
against mycobacterial infection.
PMID- 27494775
TI - Therapeutic targets and new directions for antibodies developed for ovarian
cancer.
AB - Antibody therapeutics against different target antigens are widely used in the
treatment of different malignancies including ovarian carcinomas, but this
disease still requires more effective agents. Improved understanding of the
biological features, signaling pathways, and immunological escape mechanisms
involved in ovarian cancer has emerged in the past few years. These advances,
including an appreciation of the cross-talk between cancer cells and the
patient's immune system, have led to the identification of new targets. In turn,
potential antibody treatments with various mechanisms of action, including immune
activation or toxin-delivery, that are directed at these targets have been
developed. Here, we identify established as well as novel targets for antibodies
in ovarian cancer, and discuss how they may provide fresh opportunities to
identify interventions with enhanced therapeutic potential.
PMID- 27494778
TI - Surgical Treatment of Subretinal Fibrosis Caused Macular Detachment in Vogt
Koyanagi-Harada Disease: A Pioneer Study.
AB - PURPOSE: To describe surgical outcomes of macular detachment caused by subretinal
fibrosis (SRF) in Vogt-Koyanagi-Harada disease (VKH). METHODS: Retrospective
review of VKH patients who underwent SRF removal surgery. RESULTS: Seven eyes of
six VKH patients with preoperative BCVA ranging from light perception to 20/250
were included. Six eyes underwent uncomplicated SRF removal with C3F8 or silicone
oil (SO) tamponade and the following optional primary or subsequent procedures:
intravitreal injection of triamcinolone acetonide, SO removal, lensectomy, or
phacoemulsification with intraocular lens (IOL) implantation. All six eyes had
attached macula and improved BCVA at the last visit (ranging from 20/2000 to
20/67) compared to baseline; the other eye, however, showed no light perception
after surgery due to optic nerve injury. CONCLUSIONS: In VKH patients, macular
detachment caused by SRF can be treated with surgery with generally favorable
outcomes. Extreme caution should be taken to avoid optic nerve injury.
PMID- 27494779
TI - Ligand-Controlled Stereodivergent, Enantioselective Conjugate Addition of 2
Oxazoline- and 2-Thiazoline-4-carboxylate to Nitroalkene Catalyzed by Chiral
Copper Complexes.
AB - The copper-catalyzed asymmetric conjugate addition of 2-oxazoline- and 2
thiazoline 4-carboxylate to a nitroalkene proceeded to give either the syn or
anti adduct selectively in high enantiomeric excess when an appropriate chiral
ligand was used. Subsequent reduction of the nitro group followed by hydrolysis
of the oxazoline ring yielded an optically active gamma-lactam of protected alpha
quaternary serine derivative.
PMID- 27494781
TI - Nerve transfers for restoration of finger flexion in patients with tetraplegia.
AB - OBJECTIVE The purpose of this paper was to report the authors' results with
finger flexion restoration by nerve transfer in patients with tetraplegia.
METHODS Surgery was performed for restoration of finger flexion in 17 upper limbs
of 9 patients (8 male and 1 female) at a mean of 7.6 months (SD 4 months) after
cervical spinal cord injury. The patients' mean age at the time of surgery was 28
years (SD 15 years). The motor level according to the ASIA (American Spinal
Injury Association) classification was C-5 in 4 upper limbs, C-6 in 10, and C-7
in 3. In 3 upper limbs, the nerve to the brachialis was transferred to the
anterior interosseous nerve (AIN), which was separated from the median nerve from
the antecubital fossa to the midarm. In 5 upper limbs, the nerve to the
brachialis was transferred to median nerve motor fascicles innervating finger
flexion muscles in the midarm. In 4 upper limbs, the nerve to the brachioradialis
was transferred to the AIN. In the remaining 5 upper limbs, the nerve to the
extensor carpi radialis brevis (ECRB) was transferred to the AIN. Patients were
followed for an average of 16 months (SD 6 months). At the final evaluation the
range of finger flexion and strength were estimated by manual muscle testing
according to the British Medical Research Council scale. RESULTS Restoration of
finger flexion was observed in 4 of 8 upper limbs in which the nerve to the
brachialis was used as a donor. The range of motion was incomplete in all 5 of
these limbs, and the strength was M3 in 3 limbs and M4 in 1 limb. Proximal
retrograde dissection of the AIN was associated with better outcomes than
transfer of the nerve to the brachialis to median nerve motor fascicles in the
arm. After the nerve to the brachioradialis was transferred to the AIN,
incomplete finger flexion with M4 strength was restored in 1 limb; the remaining
3 limbs did not show any recovery. Full finger flexion with M4 strength was
demonstrated in all 5 upper limbs in which the nerve to the ECRB was transferred
to the AIN. No functional downgrading of elbow flexion or wrist extension
strength was observed. CONCLUSIONS In patients with tetraplegia, finger flexion
can be restored by nerve transfer. Nerve transfer using the nerve to the ECRB as
the donor nerve produced better recovery of finger flexion in comparison with
nerve transfer using the nerve to the brachialis or brachioradialis.
PMID- 27494780
TI - Comparison of laboratory and field testing performance evaluations of siloxane
polyurethane fouling-release marine coatings.
AB - A series of eight novel siloxane-polyurethane fouling-release (FR) coatings were
assessed for their FR performance in both the laboratory and in the field.
Laboratory analysis included adhesion assessments of bacteria, microalgae,
macroalgal spores, adult barnacles and pseudobarnacles using high-throughput
screening techniques, while field evaluations were conducted in accordance with
standardized testing methods at three different ocean testing sites over the
course of six-months exposure. The data collected were subjected to statistical
analysis in order to identify potential correlations. In general, there was good
agreement between the laboratory screening assays and the field assessments, with
both regimes clearly distinguishing the siloxane-polyurethane compositions
comprising monofunctional poly(dimethyl siloxane) (PDMS) (m-PDMS) as possessing
superior, broad-spectrum FR properties compared to those prepared with
difunctional PDMS (d-PDMS). Of the seven laboratory screening techniques, the
Cellulophaga lytica biofilm retraction and reattached barnacle (Amphibalanus
amphitrite) adhesion assays were shown to be the most predictive of broad
spectrum field performance.
PMID- 27494782
TI - Magnetic resonance imaging-based measures predictive of short-term surgical
outcome in patients with Chiari malformation Type I: a pilot study.
AB - OBJECTIVE This study identifies quantitative imaging-based measures in patients
with Chiari malformation Type I (CM-I) that are associated with positive outcomes
after suboccipital decompression with duraplasty. METHODS Fifteen patients in
whom CM-I was newly diagnosed underwent MRI preoperatively and 3 months
postoperatively. More than 20 previously described morphological and
physiological parameters were derived to assess quantitatively the impact of
surgery. Postsurgical clinical outcomes were assessed in 2 ways, based on
resolution of the patient's chief complaint and using a modified Chicago Chiari
Outcome Scale (CCOS). Statistical analyses were performed to identify measures
that were different between the unfavorable- and favorable-outcome cohorts.
Multivariate analysis was used to identify the strongest predictors of outcome.
RESULTS The strongest physiological parameter predictive of outcome was the
preoperative maximal cord displacement in the upper cervical region during the
cardiac cycle, which was significantly larger in the favorable-outcome subcohorts
for both outcome types (p < 0.05). Several hydrodynamic measures revealed
significantly larger preoperative-to-postoperative changes in the favorable
outcome subcohort. Predictor sets for the chief-complaint classification included
the cord displacement, percent venous drainage through the jugular veins, and
normalized cerebral blood flow with 93.3% accuracy. Maximal cord displacement
combined with intracranial volume change predicted outcome based on the modified
CCOS classification with similar accuracy. CONCLUSIONS Tested physiological
measures were stronger predictors of outcome than the morphological measures in
patients with CM-I. Maximal cord displacement and intracranial volume change
during the cardiac cycle together with a measure that reflects the cerebral
venous drainage pathway emerged as likely predictors of decompression outcome in
patients with CM-I.
PMID- 27494783
TI - Conflicting calculations of pelvic incidence and pelvic tilt secondary to
transitional lumbosacral anatomy (lumbarization of S-1): case report.
AB - Advancements in the understanding of adult spinal deformity have led to a greater
awareness of the role of the pelvis in maintaining sagittal balance and
alignment. Pelvic incidence has emerged as a key radiographic measure and should
closely match lumbar lordosis. As proper measurement of the pelvic incidence
requires accurate identification of the S-1 endplate, lumbosacral transitional
anatomy may lead to errors. The purpose of this study is to demonstrate how
lumbosacral transitional anatomy may lead to errors in the measurement of pelvic
parameters. The current case highlights one of the potential complications that
can be avoided with awareness. The authors report the case of a 61-year-old man
who had undergone prior lumbar surgeries and then presented with symptomatic
lumbar stenosis and sagittal malalignment. Radiographs showed a lumbarized S-1.
Prior numbering of the segments in previous surgical and radiology reports led to
a pelvic incidence calculation of 61 degrees . Corrected numbering of the
segments using the lumbarized S-1 endplate led to a pelvic incidence calculation
of 48 degrees . Without recognition of the lumbosacral anatomy, overcorrection of
the lumbar lordosis might have led to negative sagittal balance and the
propensity to develop proximal junction failure. This case illustrates that
improper identification of lumbosacral transitional anatomy may lead to errors
that could affect clinical outcome. Awareness of this potential error may help
improve patient outcomes.
PMID- 27494784
TI - Contralateral psoas hematoma after minimally invasive, lateral retroperitoneal
transpsoas lumbar interbody fusion: a multicenter review of 3950 lumbar levels.
AB - OBJECTIVE Minimally invasive lateral lumbar interbody fusion (LLIF) via the
retroperitoneal transpsoas approach is a technically demanding procedure with a
multitude of potential complications. A relatively unknown complication is the
contralateral psoas hematoma. The authors speculate that injury occurs from
segmental vessel injury at the time of contralateral annulus release; however,
this is not fully understood. In this multicenter retrospective review, the
authors report the incidence of this contralateral complication and its
neurological sequelae. METHODS This study was a retrospective chart review of all
minimally invasive LLIF performed at participating institutions from 2008 to
2014. Exclusion criteria included an underlying diagnosis of trauma or neoplasia
as well as lateral corpectomies or anterior column releases. Single-level,
multilevel, and stand-alone constructs were included. All patients underwent
preoperative MRI. Follow-up was at least 12 months. All complications and
clinical outcomes were self-reported by each surgeon. RESULTS There were 3950
lumbar interbody cages placed via the retroperitoneal transpsoas approach, with 7
cases (0.18% incidence) of symptomatic contralateral psoas hematoma, 3 of which
required reoperation for hematoma evacuation. Neurological outcome did not
improve after reoperation. Reoperation occurred an average of 1 month after the
initial operation due to a delay in diagnosis. In 1 case, segmental artery injury
was confirmed at the time of surgery; in the others, segmental vessel injury was
suspected, although it could not be confirmed. Neurological deficits persisted in
3 patients while the others remained neurologically intact. Two patients were
receiving antiplatelet therapy prior to the procedure. CONCLUSIONS The
contralateral psoas hematoma is a rare complication suspected to occur from
segmental vessel injury during contralateral annulus release. Detailed review of
preoperative imaging for aberrant vessel anatomy may prevent injury and
subsequent neurological deficit.
PMID- 27494785
TI - Factors associated with increased healthcare utilization among adults with
asthma.
AB - OBJECTIVE: To evaluate determinants of increased emergency room (ER) visit and
hospitalization among adults with asthma, with emphasis on the role of
psychological distress, self-efficacy, and obesity. METHODS: For analysis 2009,
2011/2012 California Health Interview Survey was used. Adults who reported
lifetime asthma were selected. Association between ER and overnight hospital stay
with population characteristics were conducted using chi-square analysis.
Multivariable binary logistic regression models, taking into account control
variables, were utilized to assess the relationship between ER visit or overnight
hospital stay with that of psychological distress, self-efficacy, and obesity.
RESULTS: Odds of ER visits were higher among those with mild-to-moderate
psychological distress (adjusted odds ratio [aOR] = 1.94, 95% CI: 1.28, 2.94),
and among those with serious psychological distress (aOR = 2.62, 95% CI: 1.65,
4.16). Mild-to-moderate distress was associated with two-fold increase in
hospital overnight stay (aOR = 2.05, 95% CI: 1.29, 3.25). Adults with asthma who
reported low self-efficacy had increased ER visits (aOR = 6.21, 95% CI: 3.63,
10.65) and hospitalization (aOR = 4.13, 95% CI: 2.63, 6.49). Finally, adults who
had asthma and were obese had higher odds of ER visits (aOR = 1.60, 95% CI: 1.20,
2.13). CONCLUSIONS: Healthcare utilization is higher among asthma patients with
psychological distress, low self-efficacy, and obesity. Interventions, such as
incorporation of integrated care models, are critical to ensure early screening
of mental health status among such patients. In addition, there is a need for
patient education and improved weight management among adults with asthma.
PMID- 27494786
TI - Investigating a persistent odor at an aircraft seat manufacturer.
AB - An aircraft seat manufacturing company requested a NIOSH health hazard evaluation
to help identify a strong odor that had persisted throughout the facility for
over a year. Employees reported experiencing health effects thought to be related
to the odor. We collected and analyzed area air samples for volatile organic
compounds, endotoxin, bacterial and fungal metagenome, and metalworking fluid
aerosol. Bulk metalworking fluid samples were analyzed for endotoxin, bacterial
and fungal metagenome, and viable bacteria and fungus. We also evaluated the
building ventilation systems and water diversion systems. Employees underwent
confidential medical interviews about work practices, medical history, and health
concerns. Based on our analyses, the odor was likely 2-methoxy-3,5
dimethylpyrazine. This pyrazine was found in air samples across the facility and
originated from bacteria in the metalworking fluid. We did not identify bacteria
known to produce the compound but bacteria from the same Proteobacteria order
were found as well as bacteria from orders known to produce other pyrazines.
Chemical and biological contaminants and odors could have contributed to health
symptoms reported by employees, but it is likely that the symptoms were caused by
several factors. We provided several recommendations to eliminate the odor
including washing and disinfecting the metalworking machines and metalworking
fluid recycling equipment, discarding all used metalworking fluid, instituting a
metalworking fluid maintenance program at the site, and physically isolating the
metalworking department from other departments.
PMID- 27494787
TI - Effect of Chronic Medical Conditions in Veterans with Multiple Sclerosis on Long
Term Disability.
AB - BACKGROUND The goal of this observational study was to examine the effect of
common chronic medical conditions (CMCs) on long-term disability (activity
limitation) in veterans already diagnosed with multiple sclerosis (MS). MATERIAL
AND METHODS We retrospectively reviewed the electronic charts of 124 veterans
with MS who have been regularly followed in our MS clinic for 10 or more years.
General linear model analysis examined whether MS-related severity as measured by
the Expanded Disability Status Scale (EDSS) and the presence of CMCs affected
long-term disability as measured by the total score on the Functional
Independence Measure (TFIM). RESULTS Commonly encountered CMCs were increased BMI
(61%), hyperlipidemia (78%), hypertension (65%), current smokers (47%), and
arthritis/arthralgia (24%). Results suggest that the number of CMCs was not
predictive of final TFIM scores; of the variables examined, only initial EDSS
score was predictive of final TFIM scores. CONCLUSIONS The presence of CMCs did
not affect the long-term disability in veterans diagnosed with MS, this was due
mainly to CMCs being closely monitored and co-treated with other medical
specialties.
PMID- 27494788
TI - Research tasks as part of the general practice clerkship in undergraduate medical
education - a pilot project on feasibility and acceptance.
AB - OBJECTIVE: To assess the integration of a research task performed by students
during their two-week clerkship in general practice. METHODS: Students were
assigned to interview five patients with coronary heart disease using a
standardised questionnaire focusing on potential interaction of medications with
statins. Acceptance and feasibility was assessed by means of a questionnaire
survey of teaching physicians (n = 20) and students (n = 20). RESULTS: According
to most teaching physicians and students the recruitment of patients during the
two-week clerkship was possible, and the practice work flow was not disturbed by
the project. Both groups considered the research task on the documentation of
potential drug interactions with statins as suitable. According to the teaching
physicians the project had a learning effect for the students. In contrast, the
students graded their learning effect less highly between 'satisfactory' and
'sufficient'. The overall assessment of the project by the students was on
average 'satisfactory' and differed from the assessment by the teaching
physicians ('good'). CONCLUSIONS: Adequate informing of students and
participating physicians about the nature of the project and presenting
preliminary results of the data in a plenary session at the end of the clerkship
are essential for the acceptance of such projects.
PMID- 27494789
TI - Ab initio molecular dynamics study of an aqueous NaCl solution under an electric
field.
AB - We report on an ab initio molecular dynamics study of an aqueous NaCl solution
under the effect of static electric fields. We found that at low-to-moderate
field intensity regimes chlorine ions have a greater mobility than sodium ions
which, being a sort of "structure makers", are able to drag their own
coordination shells. However, for field strengths exceeding 0.15 V A(-1) the
mobility of sodium ions overcomes that of chlorine ions as both types of ions do
actually escape from their respective hydration cages. The presence of charged
particles lowers the water dissociation threshold (i.e., the minimum field
strength which induces a transfer of protons) from 0.35 V A(-1) to 0.25 V A(-1);
moreover, a protonic current was also recorded at the estimated dissociation
threshold of the solution. The behaviour of the current-voltage diagram of the
protonic response to the external electric field is Ohmic as in pure water, with
a resulting protonic conductivity of about 2.5 S cm(-1). This value is
approximately one third of that estimated in pure water (7.8 S cm(-1)), which
shows that the partial breaking of hydrogen bonds induced by the solvated ions
hinders the migration of protonic defects. Finally, the conductivity of Na(+) and
Cl(-) ions (0.2 S cm(-1)) is in fair agreement with the available experimental
data for a solution molarity of 1.7 M.
PMID- 27494790
TI - Acceptability of GM foods among Pakistani consumers.
AB - In Pakistan majority of the consumers do not have information about genetically
modified (GM) foods. In developing countries particularly in Pakistan few studies
have focused on consumers' acceptability about GM foods. Using comprehensive
primary dataset collected from 320 consumers in 2013 from Pakistan, this study
analyzes the determinants of consumers' acceptability of GM foods. The data was
analyzed by employing the bivariate probit model and censored least absolute
deviation (CLAD) models. The empirical results indicated that urban consumers are
more aware of GM foods compared to rural consumers. The acceptance of GM foods
was more among females' consumers as compared to male consumers. In addition, the
older consumers were more willing to accept GM food compared to young consumers.
The acceptability of GM foods was also higher among wealthier households. Low
price is the key factor leading to the acceptability of GM foods. The
acceptability of the GM foods also reduces the risks among Pakistani consumers.
PMID- 27494791
TI - Centennial Celebration: Endocrine Reviews Past Highlights for January and May.
PMID- 27494794
TI - Solid-Phase Synthesis of Cyclic Depsipeptides Containing a Tyrosine Phenyl Ester
Bond.
AB - The first solid-phase strategy for the synthesis of cyclic depsipeptides
containing a phenyl ester linkage in their structure is described. The key steps
of the synthesis were the formation of the phenyl ester bond and the on-resin
head-to-side-chain cyclization. The amino acid configuration significantly
influenced the formation and the stability of the cyclic depsipeptides. The
presence of a l-Tyr(1) and a d-Tyr(7) led to the most stable sequences.
PMID- 27494796
TI - Nanoscale Strategies for Light Harvesting.
AB - Recent advances and the current status of challenging light-harvesting
nanomaterials, such as semiconducting quantum dots (QDs), metal nanoparticles,
semiconductor-metal heterostructures, pi-conjugated semiconductor nanoparticles,
organic-inorganic heterostructures, and porphyrin-based nanostructures, have been
highlighted in this review. The significance of size-, shape-, and composition
dependent exciton decay dynamics and photoinduced energy transfer of QDs is
addressed. A fundamental knowledge of these photophysical processes is crucial
for the development of efficient light-harvesting systems, like photocatalytic
and photovoltaic ones. Again, we have pointed out the impact of the metal
nanoparticle-based surface energy transfer process for developing light
harvesting systems. On the other hand, metal-semiconductor hybrid nanostructures
are found to be very promising for photonic applications due to their exciton
plasmon interactions. Potential light-harvesting systems based on dye-doped pi
conjugated semiconductor polymer nanoparticles and self-assembled structures of
pi-conjugated polymer are highlighted. We also discuss the significance of
porphyrin-based nanostructures for potential light-harvesting systems. Finally,
the future perspective of this research field is given.
PMID- 27494797
TI - Use of panel testing for detection of antinuclear antibody in a resource-limited
setting: an appraisal.
AB - OBJECTIVES: Despite an increase in the incidence of systemic connective tissue
diseases (CTD), panel testing for detection of antinuclear antibodies (ANA) is
not a routine practice in many health centers of the Indian subcontinent.
Consequently, the data on its significance is scanty. METHODS: To evaluate
utility of panel testing, line immunoassay (LIA) and indirect immunofluorescence
antinuclear antibody test (IIF-ANA) were performed in 321 cases of CTD. RESULTS:
Out of 321 serum samples screened by the above tests, 227 were positive and 18
were negative by both LIA and IIF-ANA. Additional 11/321 (3.4%) cases were picked
up by LIA. SSA was most common specificity in these cases followed by SSA/SSB,
SSB, Ro-52, Jo-1, dsDNA and nRNP/Sm. CONCLUSION: Use of LIA along with IF-ANA and
ELISA improves sensitivity of CTD screening.
PMID- 27494795
TI - Preparation and quantification of the total phenolic products in Citrus fruit
using solid-phase extraction coupled with high-performance liquid chromatography
with diode array and UV detection.
AB - Citrus fruit is an important health-promoting food that is rich in dietary
phenolic metabolites. Traditional Chinese medicines, such as Zhishi and Zhiqiao,
come from young and immature fruits of Citrus cultivars. The preparation of
diversified bioactive phenolic products and establishment of the corresponding
quality control methodology are challenging and necessary. In the current study,
four types of solid-phase extraction sorbents for the enrichment and clean-up of
the phenolic matrix were evaluated. A solid-phase extraction column coated with
Strata-X was finally used in the procedure. Twenty phenolic compounds were
selected to evaluate the extraction performances of the sorbents using high
performance liquid chromatography analysis. Under the optimized conditions, good
linearities were obtained with R2 more than 0.9996 for all analytes with LODs of
0.04-1.012 MUg/g. Intra- and interday relative standard deviation values were
less than 3%, and the recovery was equal to or higher than 90.02%. Compared to
non-solid-phase extraction process, the content of total phenolic products was
elevated 35.55-68.48% with solid-phase extraction. Finally, the developed and
validated method was successfully applied to the discrimination of Zhishi samples
from different species as well as Zhishi and Zhiqiao samples in different
development stages.
PMID- 27494798
TI - Influenza epidemiology, vaccine coverage and vaccine effectiveness in children
admitted to sentinel Australian hospitals in 2014: the Influenza Complications
Alert Network (FluCAN).
AB - The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based
surveillance programme operating in all states and territories in Australia. We
summarise the epidemiology of children hospitalised with laboratory-confirmed
influenza in 2014 and reports on the effectiveness of inactivated trivalent
inactivated vaccine (TIV) in children. In this observational study, cases were
defined as children admitted with acute respiratory illness (ARI) with influenza
confirmed by PCR. Controls were hospitalised children with ARI testing negative
for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio
of vaccination in influenza positive cases compared with test-negative controls
using conditional logistic regression models. From April until October 2014, 402
children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1
year, 16% were Indigenous, and 39% had underlying conditions predisposing to
severe influenza. Influenza A was detected in 90% of cases of influenza;
influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases)
followed by A(H3N2) (32/141). Only 15% of children with influenza received
antiviral therapy. The adjusted VE of one or more doses of TIV for preventing
hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI):
11.6-77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6% , 95%
CI: 36.0-98.9%) yet appeared poor against H3N2. In summary, the 2014 southern
hemisphere TIV was moderately effective against severe influenza in children.
Significant VE was observed against influenza A(H1N1)pdm09.
PMID- 27494800
TI - The Kondo temperature of a two-dimensional electron gas with Rashba spin-orbit
coupling.
AB - We use the Hirsch-Fye quantum Monte Carlo method to study the single magnetic
impurity problem in a two-dimensional electron gas with Rashba spin-orbit
coupling. We calculate the spin susceptibility for various values of spin-orbit
coupling, Hubbard interaction, and chemical potential. The Kondo temperatures for
different parameters are estimated by fitting the universal curves of spin
susceptibility. We find that the Kondo temperature is almost a linear function of
Rashba spin-orbit energy when the chemical potential is close to the edge of the
conduction band. When the chemical potential is far away from the band edge, the
Kondo temperature is independent of the spin-orbit coupling. These results
demonstrate that, for single impurity problems in this system, the most important
reason to change the Kondo temperature is the divergence of density of states
near the band edge, and the divergence is induced by the Rashba spin-orbit
coupling.
PMID- 27494799
TI - Effectiveness of repetitive trancranial or peripheral magnetic stimulation in
neuropathic pain.
AB - PURPOSE: Maladaptive plasticity in the sensorimotor system, following
neurological lesions or diseases, plays a central role in the generation and
maintenance of neuropathic pain. Repetitive magnetic stimulation of the central
and peripheral nervous system has gained relevance as noninvasive approach for
neuromodulation and pain relief. Systematic reviews that evaluate the
effectiveness and specificity of different protocols of repetitive magnetic
stimulation to control neuropathic pain in clinical populations have the
potential to improve the therapeutic applicability of this technique. METHODS:
Studies whose primary goal was to evaluate the effectiveness of repetitive
magnetic stimulation for the treatment of various types of neuropathic pain
published in PubMed until August 2015 have been included in this systematic
review. RESULTS: A total of 39 articles fulfilling the inclusion criteria were
analyzed of which 37 studies investigated pain modulation using repetitive
magnetic stimulation over the motor or non-motor cortices and two studies
evaluated pain modulation using repetitive peripheral magnetic stimulation
protocols. CONCLUSIONS: Repetitive transcranial magnetic stimulation of the
primary motor cortex using high frequency stimulation protocols can effectively
reduce neuropathic pain, particularly in individuals with pain related to non
cerebral lesions. The application of multiple sessions can lead to long-lasting
pain modulation and cumulative effects. Implications for Rehabilitation
Maladaptive plasticity plays a central role in sensitization of nociceptive
pathways, generation and maintainance of neuropathic pain; Most neuropathic pain
conditions are refractory to pharmacological therapies; Repetitive magnetic
stimulation of the central and peripheral nervous system has gained relevance as
noninvasive approach for neuromodulation and pain relief.
PMID- 27494801
TI - Substrate Engineering Enabling Fluorescence Droplet Entrapment for IVC-FACS-Based
Ultrahigh-Throughput Screening.
AB - In vitro compartmentalization-based fluorescence-activated cell sorting (IVC
FACS) is a powerful screening tool for directed evolution of enzymes. However,
the efficiency of IVC-FACS is limited by the tendency of the fluorescent reporter
to diffuse out of the droplets, which decouples the genotype and phenotype of the
target gene. Herein we present a new strategy called fluorescence droplet
entrapment (FDE) to solve this problem. The substrate is designed with a polarity
that enables it to pass through the oil phase, react with the enzyme and generate
an oil-impermeable and fluorescent product that remains entrapped inside the
droplet. Several FDE substrates were designed, using two distinct substrate
engineering strategies, for the detection of phosphotriesterases,
carboxylesterases, and glycosidases activities. Model screening assays in which
rare phosphotriesterase-active cells were enriched from large excesses of
inactive cells showed that the enrichment efficiency achievable using an FDE
substrate was as high as 900-fold: the highest yet reported in such an IVC-FACS
system. Thus, FDE provides a means to tightly control the onset of the enzymatic
reaction, minimize droplet cross-talk, and lower the background fluorescence. It
therefore may serve as a useful strategy for the IVC-FACS screening of enzymes,
antibodies, and other proteins.
PMID- 27494803
TI - The synthesis of a pyridine-N-oxide isophthalamide rotaxane utilizing
supplementary amide hydrogen bond interactions.
AB - The synthesis of a pyridine-N-oxide containing rotaxane, not requiring an
additional ionic template, has been achieved in 32% yield. Successful rotaxane
formation is dependent upon the structure of the isophthalamide macrocycle used,
an observation which has been rationalised by a combination of NMR spectroscopy,
X-ray crystallography and computational modelling.
PMID- 27494802
TI - Molecular docking and dynamics simulation study of flavonoids as BET bromodomain
inhibitors.
AB - Bromodomains (BRDs) are the epigenetic proteins responsible for transcriptional
regulation through its interaction with methylated or acetylated histone
residues. The lysine residues of Bromodomain-1 (BD1) of Brd4 undergo epsilon-N
Acetylation posttranslational modifications to control transcription of genes.
Due to its role in diverse cellular functions, Brd4 of bromodomain family, was
considered as a prominent target for many diseases such as cancer, obesity,
kidney disease, lung fibrosis, inflammatory diseases, etc. In this study, an
attempt has been made to screen compounds from flavonoids and extended flavonoids
libraries targeting acetylated lysine (KAc) binding site of BD1 of Brd4 using
docking and molecular dynamics simulations. Two different docking programs
AutoDock and Glide were used to compare their suitability for the receptor.
Interestingly, in both the docking programs, the screened flavonoids have
occupied the same binding pocket confirming the selection of active site. Further
the MMGBSA binding free energy calculations and ADME analysis were carried out on
screened compounds to establish their anti-cancerous properties. We have
identified a flavonoid which shows docking and Glide e-model score comparatively
much higher than those of already reported known inhibitors against Brd4. The
protein-ligand complex with top-ranked flavonoid was used for dynamics simulation
study for 50 ns in order to validate its stability inside the active site of Brd4
receptor. The results provide valuable information for structure-based drug
design of Brd4 inhibitors.
PMID- 27494804
TI - Trait Variance and Response Style Variance in the Scales of the Personality
Inventory for DSM-5 (PID-5).
AB - Using self- and observer reports on the Personality Inventory for DSM-5 (PID-5)
and the HEXACO Personality Inventory-Revised (HEXACO-PI-R), we identified for
each inventory several trait dimensions (each defined by both self- and observer
reports on the facet-level scales belonging to the same domain) and 2 source
dimensions (each defined by self-reports or by observer reports, respectively, on
all facet-level scales). Results (N = 217) showed that the source dimensions of
the PID-5 were very large (much larger than those of the HEXACO-PI-R), and
suggest that self-report (or observer report) response styles substantially
inflate the intercorrelations and the alpha reliabilities of the PID-5 scales. We
discuss the meaning and the implications of the large PID-5 source components,
and we suggest some methods of controlling their influence.
PMID- 27494805
TI - Feature-based multi-resolution registration of immunostained serial sections.
AB - The form and exact function of the blood vessel network in some human organs,
like spleen and bone marrow, are still open research questions in medicine. In
this paper, we propose a method to register the immunohistological stainings of
serial sections of spleen and bone marrow specimens to enable the visualization
and visual inspection of blood vessels. As these vary much in caliber, from
mesoscopic (millimeter-range) to microscopic (few micrometers, comparable to a
single erythrocyte), we need to utilize a multi-resolution approach. Our method
is fully automatic; it is based on feature detection and sparse matching. We
utilize a rigid alignment and then a non-rigid deformation, iteratively dealing
with increasingly smaller features. Our tool pipeline can already deal with
series of complete scans at extremely high resolution, up to 620 megapixels. The
improvement presented increases the range of represented details up to smallest
capillaries. This paper provides details on the multi-resolution non-rigid
registration approach we use. Our application is novel in the way the alignment
and subsequent deformations are computed (using features, i.e. "sparse"). The
deformations are based on all images in the stack ("global"). We also present
volume renderings and a 3D reconstruction of the vascular network in human spleen
and bone marrow on a level not possible before. Our registration makes easy
tracking of even smallest blood vessels possible, thus granting experts a better
comprehension. A quantitative evaluation of our method and related state of the
art approaches with seven different quality measures shows the efficiency of our
method. We also provide z-profiles and enlarged volume renderings from three
different registrations for visual inspection.
PMID- 27494806
TI - A split recognition mode combined with cascade signal amplification strategy for
highly specific, sensitive detection of microRNA.
AB - MicroRNAs (miRNAs) are vital for many biological processes and have been regarded
as cancer biomarkers. Specific and sensitive detection of miRNAs is essential for
cancer diagnosis and therapy. Herein, a split recognition mode combined with
cascade signal amplification strategy is developed for highly specific and
sensitive detection of miRNA. The split recognition mode possesses two specific
recognition processes, which are based on toehold-mediated strand displacement
reaction (TSDR) and direct hybridization reaction. Two recognition probes,
hairpin probe (HP) with overhanging toehold domain and assistant probe (AP), are
specially designed. Firstly, the toehold domain of HP and AP recognize part of
miRNA simultaneously, accompanied with TSDR to unfold the HP and form the stable
DNA Y-shaped junction structure (YJS). Then, the AP in YJS can further act as
primer to initiate strand displacement amplification, releasing numerous trigger
sequences. Finally, the trigger sequences hybridize with padlock DNA to initiate
circular rolling circle amplification and generate enhanced fluorescence
responses. In this strategy, the dual recognition effect of split recognition
mode guarantees the excellent selectivity to discriminate let-7b from high
homology sequences. Furthermore, the high amplification efficiency of cascade
signal amplification guarantees a high sensitivity with the detection limit of
3.2 pM and the concentration of let-7b in total RNA sample extracted from Hela
cells is determined. These results indicate our strategy will be a promising
miRNA detection strategy in clinical diagnosis and disease treatment.
PMID- 27494807
TI - Induced nanoparticle aggregation for short nucleic acid quantification by
depletion isotachophoresis.
AB - A rapid (<20min) gel-membrane biochip platform for the detection and
quantification of short nucleic acids is presented based on a sandwich assay with
probe-functionalized gold nanoparticles and their separation into concentrated
bands by depletion-generated gel isotachophoresis. The platform sequentially
exploits the enrichment and depletion phenomena of an ion-selective cation
exchange membrane created under an applied electric field. Enrichment is used to
concentrate the nanoparticles and targets at a localized position at the gel
membrane interface for rapid hybridization. The depletion generates an
isotachophoretic zone without the need for different conductivity buffers, and is
used to separate linked nanoparticles from isolated ones in the gel medium and
then by field-enhanced aggregation of only the linked particles at the depletion
front. The selective field-induced aggregation of the linked nanoparticles during
the subsequent depletion step produces two lateral-flow like bands within 1cm for
easy visualization and quantification as the aggregates have negligible
electrophoretic mobility in the gel and the isolated nanoparticles are
isotachophoretically packed against the migrating depletion front. The detection
limit for 69-base single-stranded DNA targets is 10 pM (about 10 million copies
for our sample volume) with high selectivity against nontargets and a three
decade linear range for quantification. The selectivity and signal intensity are
maintained in heterogeneous mixtures where the nontargets outnumber the targets
10,000 to 1. The selective field-induced aggregation of DNA-linked nanoparticles
at the ion depletion front is attributed to their trailing position at the
isotachophoretic front with a large field gradient.
PMID- 27494808
TI - A G-quadruplex-selective luminescent probe with an anchor tail for the switch-on
detection of thymine DNA glycosylase activity.
AB - Thymine DNA glycosylase (TDG) performs essential functions in maintaining genetic
integrity and epigenetic regulation, which also plays an essential role in DNA
demethylation. In this work, the novel iridium(III) complex 1 with an anchor tail
was synthesized and employed to construct a G-quadruplex-based assay for
detecting TDG activity in aqueous solution by using the mismatched base excising
property of TDG with T4 DNA ligase and phi29 DNA polymerase, in concert with the
rolling circle amplification (RCA) strategy. The assay achieved a detection limit
of 0.048UmL(-)(1) (0.012ngmL(-1)), and showed high selectivity towards TDG even
in the presence of other proteins and enzymes. Additionally, the assay could
function in diluted cellular debris.
PMID- 27494809
TI - Modulating luminescence of Tb(3+) with biomolecules for sensing heparin and its
contaminant OSCS.
AB - The detection of heparin (Hep) and its contaminant oversulfated chondroitin
sulfate (OSCS) is of great importance in clinics but remains challenging. Here,
we report a sensitive and selective time-resolved luminescence (TRL) biosensing
system for Hep by modulating the photoluminescence of Tb(3+) with guanine-rich
ssDNA and Hep-specific AG73 peptide (RKRLQVQLSIRT). With the developed system,
Hep including both unfractionated Hep (UFH) and the low molecular weight Hep
(LMWH) has been successfully detected with a satisfactory detection limit. Owing
to the highly specific interaction between Hep and AG73 peptide, major
interfering substances in Hep detection, such as Hep analogs of chondrotin
sulfate (Chs) and hyaluronic acid (HA), did not interfere with Hep detection. The
established TRL sensing system was then successfully used for monitoring Hep
metabolism in living rats by microdialysis. Moreover, the proposed TRL sensing
system was further applied to analyze OSCS contaminant in Hep with heparinases
treatment by exploring the inhibition effects of OSCS on the activity of
heparinases. As low as 0.002% of OSCS in Hep was identified.
PMID- 27494810
TI - Magnetic nanowires for rapid and ultrasensitive isolation of DNA from cervical
specimens for the detection of multiple human papillomaviruses genotypes.
AB - Detecting human papillomavirus (HPV) is central in diagnosing and monitoring HPV
related disease. However, limited sensitivity and the wide variability of the HPV
genome pose challenges in the identification of HPV genes, particularly high-risk
types. This study reports the development of polyethyleneimine-conjugated
magnetic nanowires (PEI-MNWs) and their use in the isolation, identification, and
analysis of multiple genotypes of HPV DNA from cervical cancer specimens. The
nanowires are electrochemically doped with a high density of magnetic
nanoparticles and biotin moieties during potentiostatic deposition, thereby
allowing conjugating cationic branched polymers to direct the attachment of
negatively charged DNA molecules with strong magnetic response. For proof of
concept, the rapid and ultrasensitive isolation of HPV DNA is performed at
concentrations as low as 10pg/mL with an efficiency of >95%. For clinical
optimization, the analytical and clinical sensitivity of PEI-MNWs is compared
with that of the Roche Cobas 4800 HPV Test and demonstrates excellent correlation
for multiple HPV DNA genotypes with superior threshold cycle values. The high
sensitivity, specificity, and good reproducibility of PEI-MNWs are particularly
well suited for the recovery of DNA and provide significant and clinically
meaningful evidence for the early detection and treatment of HPV-associated
cancers.
PMID- 27494811
TI - Low potential detection of indole-3-acetic acid based on the peroxidase-like
activity of hemin/reduced graphene oxide nanocomposite.
AB - An amperometric sensor was firstly established for the detection of indole-3
acetic acid (IAA) at low potential based on the hemin/reduced graphene oxide
(hemin/rGO) composite. The hemin/rGO nanocomposite was prepared by a simple and
facile hydrothermal method without using any reducing agent. It exhibited
peroxidase-like activity for the catalytic oxidation of IAA in the presence of
oxygen. The consumption of oxygen has a linear relationship with the
concentration of IAA in the range from 0.1 to 43MUM and from 43 to 183MUM. The
detection limit was down to 0.074MUM. This sensor was unaffected by many
interfering substances and stable over time. Such work broadened the application
of hemin/rGO and provided a new method for IAA detection.
PMID- 27494812
TI - Simultaneous determination of 6-mercaptopruine, 6-thioguanine and dasatinib as
three important anticancer drugs using nanostructure voltammetric sensor
employing Pt/MWCNTs and 1-butyl-3-methylimidazolium hexafluoro phosphate.
AB - 6-Mercaptopurine, 6-thioguanine and dasatinib are three important anticancer
drugs with high adverse effects in human body. In this study, a Pt/MWCNTs-1-butyl
3-methylimidazolium hexafluoro phosphate-modified carbon paste electrode was
developed for the simultaneously determination of 6-mercaptopurine, 6-thioguanine
and dasatinib for the first time. The Pt/MWCNTs synthesized by polyol method and
have been characterized by transmission electron microscopy and X-ray diffraction
methods. The obtained data revealed that the electro-oxidation of 6
mercaptopurine, 6-thioguanine and dasatinib is facilitated as a novel
voltammetric sensor. After optimization of electrochemical parameters employing
this sensor at pH 8.0, the oxidation peak currents for 6-mercaptopurine, 6
thioguanine and dasatinib were found to vary linearly with their concentrations
in the range of 0.05-550MUM; 0.1-500MUM and 5.0-500MUM with detection limits of
0.009MUM, 0.05MUM and 1.0MUM respectively using square wave voltammetric method.
The modified electrode has been applied for the selective and precise analysis of
6-mercaptopurine, 6-thioguanine and dasatinib in pharmaceutical formulations and
urine samples.
PMID- 27494814
TI - A novel miniature robotic device for frameless implantation of depth electrodes
in refractory epilepsy.
AB - OBJECTIVE The authors' group recently published a novel technique for a
navigation-guided frameless stereotactic approach for the placement of depth
electrodes in epilepsy patients. To improve the accuracy of the trajectory and
enhance the procedural workflow, the authors implemented the iSys1 miniature
robotic device in the present study into this routine. METHODS As a first step, a
preclinical phantom study was performed using a human skull model, and the
accuracy and timing between 5 electrodes implanted with the manual technique and
5 with the aid of the robot were compared. After this phantom study showed an
increased accuracy with robot-assisted electrode placement and confirmed the
robot's ability to maintain stability despite the rotational forces and the
leverage effect from drilling and screwing, patients were enrolled and analyzed
for robot-assisted depth electrode placement at the authors' institution from
January 2014 to December 2015. All procedures were performed with the S7 Surgical
Navigation System with Synergy Cranial software and the iSys1 miniature robotic
device. RESULTS Ninety-three electrodes were implanted in 16 patients (median age
33 years, range 3-55 years; 9 females, 7 males). The authors saw a significant
increase in accuracy compared with their manual technique, with a median
deviation from the planned entry and target points of 1.3 mm (range 0.1-3.4 mm)
and 1.5 mm (range 0.3-6.7 mm), respectively. For the last 5 patients (31
electrodes) of this series the authors modified their technique in placing a
guide for implantation of depth electrodes (GIDE) on the bone and saw a
significant further increase in the accuracy at the entry point to 1.18 +/- 0.5
mm (mean +/- SD) compared with 1.54 +/- 0.8 mm for the first 11 patients (p =
0.021). The median length of the trajectories was 45.4 mm (range 19-102.6 mm).
The mean duration of depth electrode placement from the start of trajectory
alignment to fixation of the electrode was 15.7 minutes (range 8.5-26.6 minutes),
which was significantly faster than with the manual technique. In 12 patients,
depth electrode placement was combined with subdural electrode placement. The
procedure was well tolerated in all patients. The authors did not encounter any
case of hemorrhage or neurological deficit related to the electrode placement. In
1 patient with a psoriasis vulgaris, a superficial wound infection was
encountered. Adequate physiological recordings were obtained from all electrodes.
No additional electrodes had to be implanted because of misplacement. CONCLUSIONS
The iSys1 robotic device is a versatile and easy to use tool for frameless
implantation of depth electrodes for the treatment of epilepsy. It increased the
accuracy of the authors' manual technique by 60% at the entry point and over 30%
at the target. It further enhanced and expedited the authors' procedural
workflow.
PMID- 27494813
TI - A viscosity sensitive fluorescent dye for real-time monitoring of mitochondria
transport in neurons.
AB - We present here a viscosity sensitive fluorescent dye, namely thiophene
dihemicyanine (TDHC), that enables the specific staining of mitochondria. In
comparison to the common mitochondria tracker (Mitotracker Deep Red, MTDR), this
dye demonstrated its unique ability for robust staining of mitochondria with high
photostability and ultrahigh signal-to-noise ratio (SNR). Moreover, TDHC also
showed high sensitivity towards mitochondria membrane potential (DeltaPsim) and
intramitochondria viscosity change. Consequently, this dye was utilized in real
time monitoring of mitochondria transport in primary cortical neurons. Finally,
the Two-Photon Microscopy (TPM) imaging ability of TDHC was also demonstrated.
PMID- 27494815
TI - Repeat stereotactic radiosurgery as salvage therapy for locally recurrent brain
metastases previously treated with radiosurgery.
AB - OBJECTIVE There are a variety of salvage options available for patients with
brain metastases who experience local failure after stereotactic radiosurgery
(SRS). These options include resection, whole-brain radiation therapy, laser
thermoablation, and repeat SRS. There is little data on the safety and efficacy
of repeat SRS following local failure of a prior radiosurgical procedure. This
study evaluates the clinical outcomes and dosimetric characteristics of patients
who experienced tumor recurrence and were subsequently treated with repeat SRS.
METHODS Between 2002 and 2015, 32 patients were treated with repeat SRS for local
recurrence of >= 1 brain metastasis following initial SRS treatment. The Kaplan
Meier method was used to estimate time-to-event outcomes including overall
survival (OS), local failure, and radiation necrosis. Cox proportional hazards
analysis was performed for predictor variables of interest for each outcome.
Composite dose-volume histograms were constructed for each reirradiated lesion,
and these were then used to develop a predictive dosimetric model for radiation
necrosis. RESULTS Forty-six lesions in 32 patients were re-treated with a second
course of SRS after local failure. A median dose of 20 Gy (range 14-22 Gy) was
delivered to the tumor margin at the time of repeat SRS. Local control at 1 year
was 79% (95% CI 67%-94%). Estimated 1-year OS was 70% (95% CI 55%-88%). Twelve
patients had died at the most recent follow-up, with 8/12 patients experiencing
neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions
in 11 separate patients treated with repeat SRS were associated with symptomatic
radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%
88%). Analysis of dosimetric data revealed that the volume of a lesion receiving
40 Gy (V40Gy) was the most predictive factor for the development of radiation
necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%,
20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI
3%-28%), 0.76 cm3 (95% CI 9%-39%), 1.60 cm3 (95% CI 26%-74%). CONCLUSIONS Repeat
SRS appears to be an effective salvage option for patients with brain metastases
experiencing local failure following initial SRS treatment. This series
demonstrates durable local control and, although rates of radiation necrosis are
significant, repeat SRS may be indicated for select cases of local disease
recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this
value during treatment planning may allow for a reduction in radiation necrosis
rates.
PMID- 27494816
TI - Craniopharyngioma recurrence: the impact of tumor topography.
PMID- 27494817
TI - Vascular permeability and iron deposition biomarkers in longitudinal follow-up of
cerebral cavernous malformations.
AB - OBJECTIVE Vascular permeability and iron leakage are central features of cerebral
cavernous malformation (CCM) pathogenesis. The authors aimed to correlate
prospective clinical behavior of CCM lesions with longitudinal changes in
biomarkers of dynamic contrast-enhanced quantitative permeability (DCEQP) and
quantitative susceptibility mapping (QSM) assessed by MRI. METHODS Forty-six
patients with CCMs underwent 2 or more permeability and/or susceptibility studies
in conjunction with baseline and follow-up imaging and clinical surveillance
during a mean 12.05 months of follow-up (range 2.4-31.27 months). Based on
clinical and imaging features, cases/lesions were classified as stable, unstable,
or recovering. Associated and predictive changes in quantitative permeability and
susceptibility were investigated. RESULTS Lesional mean permeability and QSM
values were not significantly different in stable versus unstable lesions at
baseline. Mean lesional permeability in unstable CCMs with lesional bleeding or
growth increased significantly (+85.9% change; p = 0.005), while mean
permeability in stable and recovering lesions did not significantly change. Mean
lesional QSM values significantly increased in unstable lesions (+44.1% change; p
= 0.01), decreased slightly with statistical significance in stable lesions (
3.2% change; p = 0.003), and did not significantly change in recovering lesions.
Familial cases developing new lesions during the follow-up period showed a higher
background brain permeability at baseline (p = 0.001), as well as higher regional
permeability (p = 0.003) in the area that would later develop a new lesion as
compared with the homologous contralateral brain region. CONCLUSIONS In vivo
assessment of vascular permeability and iron deposition on MRI can serve as
objective and quantifiable biomarkers of disease activity in CCMs. This may be
applied in natural history studies and may help calibrate clinical trials. The 2
techniques are likely applicable in other disorders of vascular integrity and
iron leakage such as aging, hemorrhagic microangiopathy, and traumatic brain
injury.
PMID- 27494818
TI - Effectiveness of minocycline in acute white matter injury after intracerebral
hemorrhage.
AB - OBJECTIVE Intracerebral hemorrhage (ICH) is a fatal disease with high morbidity
and mortality, which may be followed by white matter injury (WMI) due to the
local oxidizing reaction induced by iron (Fe). In this study, the authors
examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI
and c-Jun N-terminal kinase (JNK) activation in rats. METHODS Thirty-six male
Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe +
minocycline. Another 36 rats had an intracaudate injection of autologous blood
and were treated with minocycline or vehicle (saline). Biomarkers of both WMI and
JNK activation were examined. RESULTS In the Fe-injection group, minocycline
suppressed WMI labeled by beta-amyloid precursor protein (beta-APP) and degraded
myelin basic protein (dMBP)/MBP ratio. Protein levels of phosphorylated-JNK were
increased after Fe injection, and could be suppressed by minocycline treatment.
In the autologous blood-injection group, beta-APP and dMBP/MBP levels increased
in the ipsilateral site compared with the contralateral site, which could be
suppressed by 7 days of minocycline intervention. CONCLUSIONS Iron plays a
critical role in WMI after ICH, which can be suppressed by minocycline through
reducing the damage induced by Fe.
PMID- 27494819
TI - Preventive effects of cilostazol against the development of shunt-dependent
hydrocephalus after subarachnoid hemorrhage.
AB - OBJECTIVE Chronic hydrocephalus develops in association with the induction of
tenascin-C (TNC), a matricellular protein, after aneurysmal subarachnoid
hemorrhage (SAH). The aim of this study was to examine if cilostazol, a selective
inhibitor of phosphodiesterase Type III, suppresses the development of chronic
hydrocephalus by inhibiting TNC induction in aneurysmal SAH patients. METHODS The
authors retrospectively reviewed the factors influencing the development of
chronic shunt-dependent hydrocephalus in 87 patients with Fisher Grade 3 SAH
using multivariate logistic regression analyses. Cilostazol (50 or 100 mg
administered 2 or 3 times per day) was administered from the day following
aneurysmal obliteration according to the preference of the attending
neurosurgeon. As a separate study, the effects of different dosages of cilostazol
on the serum TNC levels were chronologically examined from Days 1 to 12 in 38 SAH
patients with Fisher Grade 3 SAH. RESULTS Chronic hydrocephalus occurred in 12 of
36 (33.3%), 5 of 39 (12.8%), and 1 of 12 (8.3%) patients in the 0 mg/day, 100 to
200 mg/day, and 300 mg/day cilostazol groups, respectively. The multivariate
analyses showed that older age (OR 1.10, 95% CI 1.13-1.24; p = 0.012), acute
hydrocephalus (OR 23.28, 95% CI 1.75-729.83; p = 0.016), and cilostazol (OR 0.23,
95% CI 0.05-0.93; p = 0.038) independently affected the development of chronic
hydrocephalus. Higher dosages of cilostazol more effectively suppressed the serum
TNC levels through Days 1 to 12 post-SAH. CONCLUSIONS Cilostazol may prevent the
development of chronic hydrocephalus and reduce shunt surgery, possibly by the
inhibition of TNC induction after SAH.
PMID- 27494820
TI - Predictors of 30-day readmission after aneurysmal subarachnoid hemorrhage: a case
control study.
AB - OBJECTIVE Despite persisting questions regarding its appropriateness, 30-day
readmission is an increasingly common quality metric used to influence hospital
compensation in the United States. However, there is currently insufficient
evidence to identify which patients are at highest risk for readmission after
aneurysmal subarachnoid hemorrhage (SAH). The objective of this study was to
identify predictors of 30-day readmission after SAH, to focus preventative
efforts, and to provide guidance to funding agencies seeking to risk-adjust
comparisons among hospitals. METHODS The authors performed a case-control study
of 30-day readmission among aneurysmal SAH patients treated at a single center
between 2003 and 2013. To control for geographic distance from the hospital and
year of treatment, the authors randomly matched each case (30-day readmission)
with approximately 2 SAH controls (no readmission) based on home ZIP code and
treatment year. They evaluated variables related to patient demographics,
socioeconomic characteristics, comorbidities, presentation severity (e.g., Hunt
and Hess grade), and clinical course (e.g., need for gastrostomy or tracheostomy,
length of stay). Conditional logistic regression was used to identify significant
predictors, accounting for the matched design of the study. RESULTS Among 82 SAH
patients with unplanned 30-day readmission, the authors matched 78 patients with
153 nonreadmitted controls. Age, demographics, and socioeconomic factors were not
associated with readmission. In univariate analysis, multiple variables were
significantly associated with readmission, including Hunt and Hess grade (OR 3.0
for Grade IV/V vs I/II), need for gastrostomy placement (OR 2.0), length of
hospital stay (OR 1.03 per day), discharge disposition (OR 3.2 for skilled
nursing vs other disposition), and Charlson Comorbidity Index (OR 2.3 for score
>= 2 vs 0). However, the only significant predictor in the multivariate analysis
was discharge to a skilled nursing facility (OR 3.2), and the final model was
sensitive to criteria used to enter and retain variables. Furthermore, despite
the significant association between discharge disposition and readmission, less
than 25% of readmitted patients were discharged to a skilled nursing facility.
CONCLUSIONS Although discharge disposition remained significant in multivariate
analysis, most routinely collected variables appeared to be weak independent
predictors of 30-day readmission after SAH. Consequently, hospitals interested in
decreasing readmission rates may consider multifaceted, cost-efficient
interventions that can be broadly applied to most if not all SAH patients.
PMID- 27494821
TI - Contemporary analysis of the intraoperative and perioperative complications of
neurosurgical procedures performed in the sitting position.
AB - OBJECTIVE Historically, performing neurosurgery with the patient in the sitting
position offered advantages such as improved visualization and gravity-assisted
retraction. However, this position fell out of favor at many centers due to the
perceived risk of venous air embolism (VAE) and other position-related
complications. Some neurosurgical centers continue to perform sitting-position
cases in select patients, often using modern monitoring techniques that may
improve procedural safety. Therefore, this paper reports the risks associated
with neurosurgical procedures performed in the sitting position in a modern
series. METHODS The authors reviewed the anesthesia records for instances of
clinically significant VAE and other complications for all neurosurgical
procedures performed in the sitting position between January 1, 2000, and October
8, 2013. In addition, a prospectively maintained morbidity and mortality log of
these procedures was reviewed for instances of subdural or intracerebral
hemorrhage, tension pneumocephalus, and quadriplegia. Both overall and specific
complication rates were calculated in relation to the specific type of procedure.
RESULTS In a series of 1792 procedures, the overall complication rate related to
the sitting position was 1.45%, which included clinically significant VAE,
tension pneumocephalus, and subdural hemorrhage. The rate of any detected VAE was
4.7%, but the rate of VAE requiring clinical intervention was 1.06%. The risk of
clinically significant VAE was highest in patients undergoing suboccipital
craniotomy/craniectomy with a rate of 2.7% and an odds ratio (OR) of 2.8 relative
to deep brain stimulator cases (95% confidence interval [CI] 1.2-70, p = 0.04).
Sitting cervical spine cases had a comparatively lower complication rate of 0.7%
and an OR of 0.28 as compared with all cranial procedures (95% CI 0.12-0.67, p <
0.01). Sitting cervical cases were further subdivided into extradural and
intradural procedures. The rate of complications in intradural cases was
significantly higher (OR 7.3, 95% CI 1.4-39, p = 0.02) than for extradural cases.
The risk of VAE in intradural spine procedures did not differ significantly from
sitting suboccipital craniotomy/craniectomy cases (OR 0.69, 95% CI 0.09-5.4, p =
0.7). Two cases (0.1%) had to be aborted intraoperatively due to complications.
There were no instances of intraoperative deaths, although there was a single
death within 30 days of surgery. CONCLUSIONS In this large, modern series of
cases performed in the sitting position, the complication rate was low.
Suboccipital craniotomy/craniectomy was associated with the highest risk of
complications. When appropriately used with modern anesthesia techniques, the
sitting position provides a safe means of surgical access.
PMID- 27494822
TI - Endoscope-assisted transsphenoidal puncture of the cavernous sinus for
embolization of carotid-cavernous fistula in a neurosurgical hybrid operating
suite.
AB - Endovascular embolization is the treatment of choice for carotid-cavernous
fistulas (CCFs), but failure to catheterize the cavernous sinus may occur as a
result of vessel tortuosity, hypoplasia, or stenosis. In addition to conventional
transvenous or transarterial routes, alternative approaches should be considered.
The authors present a case in which a straightforward route to the CCF was
accessed via transsphenoidal puncture of the cavernous sinus in a neurosurgical
hybrid operating suite. This 82-year-old man presented with severe chemosis and
proptosis of the right eye. Digital subtraction angiography revealed a Type B CCF
with a feeding artery arising from the meningohypophyseal trunk of the right
cavernous segment of the internal carotid artery. The CCF drained through a
thrombosed right superior ophthalmic vein that ended deep in the orbit; there
were no patent sinuses or venous plexuses connecting to the CCF. An endoscope
assisted transsphenoidal puncture created direct access to the nidus for
embolization. Embolic agents were deployed through the puncture needle to achieve
complete obliteration. Endoscope-assisted transsphenoidal puncture of the
cavernous sinus is a feasible alternative to treat difficult-to-access CCFs in a
neurosurgical hybrid operating suite.
PMID- 27494823
TI - Facile Incorporation of Pd(PPh3)2Hal Substituents into Polymethines,
Merocyanines, and Perylene Diimides as a Means of Suppressing Intermolecular
Interactions.
AB - Compounds with polarizable pi systems that are susceptible to attack with
nucleophiles at C-Hal (Hal = Cl, Br) bonds react with Pd(PPh3)4 to yield net
oxidative addition. X-ray structures show that the resulting Pd(PPh3)2Hal groups
greatly reduce intermolecular pi-pi interactions. The Pd-functionalized dyes
generally exhibit solution-like absorption spectra in films, whereas their Hal
analogues exhibit features attributable to aggregation.
PMID- 27494824
TI - A population-based study of large granular lymphocyte leukemia.
AB - Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of
cytotoxic cells. T-cell LGL (T-LGL) leukemia is characterized by accumulation of
cytotoxic T cells in blood and infiltration of the bone marrow, liver or spleen.
Population-based studies have not been reported in LGL leukemia. We present
clinical characteristics, natural history and risk factors for poor survival in
patients with LGL leukemia using the Surveillance, Epidemiology, and End Results
Program (SEER) and the United States National Cancer Data Base (NCDB). LGL
leukemia is an extremely rare disease with the incidence of 0.2 cases per 1 000
000 individuals. The median age at diagnosis was 66.5 years with females likely
to be diagnosed at 3 years earlier compared with males. Analysis of patient-level
data using NCDB (n=978) showed that 45% patients with T-LGL leukemia required
some form of systemic treatment at the time of diagnosis. T-LGL leukemia patients
have reduced survival compared with general population, with a median overall
survival of 9 years. Multivariate analysis showed that age >60 years at the time
of diagnosis and the presence of significant comorbidities were independent
predictors of poor survival.
PMID- 27494825
TI - Crizotinib treatment for refractory pediatric acute myeloid leukemia with RAN
binding protein 2-anaplastic lymphoma kinase fusion gene.
PMID- 27494827
TI - The level of detail required in a deformable phantom to accurately perform
quality assurance of deformable image registration.
AB - The primary purpose of the study was to determine how detailed deformable image
registration (DIR) phantoms need to adequately simulate human anatomy and
accurately assess the quality of DIR algorithms. In particular, how many distinct
tissues are required in a phantom to simulate complex human anatomy? Pelvis and
head-and-neck patient CT images were used for this study as virtual phantoms. Two
data sets from each site were analyzed. The virtual phantoms were warped to
create two pairs consisting of undeformed and deformed images. Otsu's method was
employed to create additional segmented image pairs of n distinct soft tissue CT
number ranges (fat, muscle, etc). A realistic noise image was added to each
image. Deformations were applied in MIM Software (MIM) and Velocity deformable
multi-pass (DMP) and compared with the known warping. Images with more simulated
tissue levels exhibit more contrast, enabling more accurate results. Deformation
error (magnitude of the vector difference between known and predicted
deformation) was used as a metric to evaluate how many CT number gray levels are
needed for a phantom to serve as a realistic patient proxy. Stabilization of the
mean deformation error was reached by three soft tissue levels for Velocity DMP
and MIM, though MIM exhibited a persisting difference in accuracy between the
discrete images and the unprocessed image pair. A minimum detail of three levels
allows a realistic patient proxy for use with Velocity and MIM deformation
algorithms.
PMID- 27494829
TI - Editorial: Resurrecting the rubric 'For debate'.
PMID- 27494826
TI - Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into
Asthma Control.
AB - RATIONALE: Maintaining optimal symptom control remains the primary objective of
asthma treatment. Better understanding of the biologic underpinnings of asthma
control may lead to the development of improved clinical and pharmaceutical
approaches. OBJECTIVES: To identify molecular pathways and interrelated genes
whose differential expression was associated with asthma control. METHODS: We
performed gene set enrichment analyses of asthma control in 1,170 adults with
asthma, each with gene expression data derived from either whole blood (WB) or
unstimulated CD4+ T lymphocytes (CD4), and a self-reported asthma control score
representing either the preceding 6 months (chronic) or 7 days (acute). Our study
comprised a discovery WB cohort (n = 245, chronic) and three independent,
nonoverlapping replication cohorts: a second WB set (n = 448, acute) and two CD4
sets (n = 300, chronic; n = 77, acute). MEASUREMENTS AND MAIN RESULTS: In the WB
discovery cohort, we found significant overrepresentation of genes associated
with asthma control in 1,106 gene sets from the Molecular Signatures Database
(false discovery rate, <5%). Of these, 583 (53%) replicated in at least one
replication cohort (false discovery rate, <25%). Suboptimal control was
associated with signatures of eosinophilic and granulocytic inflammatory signals,
whereas optimal control signatures were enriched for immature lymphocytic
patterns. These signatures included two related biologic processes related to
activation by TREM-1 (triggering receptor expressed on myeloid cells 1) and
lipopolysaccharide. CONCLUSIONS: Together, these results demonstrate the
existence of specific, reproducible transcriptomic components in blood that vary
with degree of asthma control and implicate a novel biologic target (TREM-1).
PMID- 27494828
TI - Trichostatin A Inhibits Retinal Pigmented Epithelium Activation in an In Vitro
Model of Proliferative Vitreoretinopathy.
AB - PURPOSE: Proliferative vitreoretinopathy (PVR) is a blinding disorder that
develops after a retinal tear or detachment. Activation of the retinal pigmented
epithelium (RPE) is implicated in PVR; however, the mechanisms leading to
enhanced RPE proliferation, migration, and contraction remain largely unknown.
This study utilized an in vitro model of PVR to investigate the role of
acetylation in RPE activation and its contribution to the progression of this
disease. METHODS: ARPE-19 cells, primary cultures of porcine RPE, and induced
pluripotent stem cell-derived RPE (iPS-RPE) were utilized for cellular and
molecular analyses. Cells treated with transforming growth factor beta 2
(TGFbeta2; 10 ng/mL) alone or in the presence of the broad-spectrum histone
deacetylase (HDAC) inhibitor, trichostatin A (TSA; 0.1 MUM), were assessed for
contraction and migration through collagen contraction and scratch assays,
respectively. Western blotting and immunofluorescence analysis were performed to
assess alpha-smooth muscle actin (alpha-SMA) and beta-catenin expression after
TGFbeta2 treatment alone or in combination with TSA. RESULTS: TGFbeta2
significantly increased RPE cell contraction in collagen matrix and this effect
was inhibited in the presence of TSA (0.1 MUM). In agreement with these data,
immunofluorescence analysis of TSA-treated iPS-RPE wounded monolayers revealed
decreased alpha-SMA as compared with control. Scratch assays to assess wound
healing revealed TSA inhibited TGFbeta2-mediated iPS-RPE cell migration.
CONCLUSIONS: Our findings indicate a role of acetylation in RPE activation.
Specifically, the HDAC inhibitor TSA decreased RPE cell proliferation and
TGFbeta2-mediated cell contraction and migration. Further investigation of
pharmacological compounds that modulate acetylation may hold promise as
therapeutic agents for PVR.
PMID- 27494830
TI - New therapeutic strategies for invasive aspergillosis in the era of azole
resistance: how should the prevalence of azole resistance be defined?
AB - Given reports showing a high prevalence of azole resistance in Aspergillus
fumigatus, alternatives to azole therapy are discussed when a threshold of 10% of
azole-resistant environmental isolates is reached. This raises the issue of
calculation of this threshold, either on the prevalence of azole-resistant
isolates as a whole or on the prevalence of azole-resistant cases in populations
at risk of invasive aspergillosis (IA). For isolate evaluation, there are high
disparities in routine microbiological procedures for the isolation of A.
fumigatus and azole resistance detection. There are also huge differences between
the microbiological work-up for diagnosing IA. Some centres rely on galactomannan
detection alone without actively trying to culture appropriate samples, which
affects reliability of the figures on the prevalence of resistance and thus the
threshold of resistance. Moreover, reports from the laboratory could mix up
figures from completely different patient populations: frequent azole-resistant
isolates from pneumology patients and rare azole-resistant isolates from
haematology patients. Therefore, to sum isolates from different specimens and
different wards can lead to erroneous calculations for the restricted populations
at risk of developing IA. In conclusion, assessing the incidence of azole
resistance in A. fumigatus should be based on harmonized consensual
microbiological methods and reports should be restricted to IA episodes in
identified populations at risk of IA when the issue is to define an operational
threshold for modifying recommendations.
PMID- 27494831
TI - Azole resistance surveillance in Aspergillus fumigatus: beneficial or biased?
AB - Azole resistance is a growing concern with Aspergillus fumigatus, and may cause
increased mortality in patients with azole-resistant invasive aspergillosis (IA).
Microbial surveillance has been recognized as a fundamental component of
resistance management. Surveillance information may be used to inform decisions
regarding health services and research funding allocation, to guide local
infection control in hospitals and communities, and to direct local and national
drug policies and guidelines. Azole resistance frequencies have been based on
screening of unselected A. fumigatus isolates, on the number of azole-resistant
cases within a cohort of patients with a specific Aspergillus disease, or on
analysis of patients within a specific risk group. The various surveillance
approaches differ in their aims, as well as in their associated advantages and
drawbacks. Nevertheless, a wide range of azole resistance frequencies has been
reported, partly due to the denominator used. As most azole resistance is
believed to develop in the environment and, as a consequence, azole-naive
patients may present with azole-resistant aspergillosis, experts recommended a
10% resistance frequency threshold above which the standard treatment choice,
i.e. voriconazole, should be reconsidered. We believe that local resistance rates
based on Aspergillus disease and/or risk group should be leading for decisions
regarding empirical antifungal therapy in specific units. In addition, patient
factors should be considered, such as admission to the ICU. Collecting valid
surveillance data may be challenging in azole resistance due to numerous factors
that present potential biases. Surveillance research may benefit from further
standardization, which may be facilitated through the recently instituted
International Society for Human and Animal Mycology (ISHAM) Aspergillus
Resistance Surveillance Working Group.
PMID- 27494832
TI - CTX-M-15-H30Rx-ST131 subclone is one of the main causes of healthcare-associated
ESBL-producing Escherichia coli bacteraemia of urinary origin in Spain.
AB - OBJECTIVES: The objective of this study was to assess the prevalence and
molecular epidemiology of ESBL-producing Escherichia coli causing healthcare
associated (HCA) and community-associated (CA) bacteraemia of urinary origin
(BUO) in Spain. METHODS: An observational cohort study was conducted at eight
hospitals from different Spanish geographical areas (2010-11). BUO episodes (n =
425) were classified as HCA (n = 215) and CA (n = 210), and one blood isolate per
episode was collected. Susceptibility testing was performed, ESBLs were screened
by double-disc diffusion test and ESBL and OXA-1 genes were characterized (PCR
and sequencing). Population structure (phylogenetic groups, XbaI-PFGE and MLST)
and ST131 subtyping (PCR) were determined. Virulence genes were detected by PCR
and virulence score, profiles and extraintestinal pathogenic E. coli (ExPEC)
status calculated. RESULTS: ESBL-producing E. coli prevalence was 9.2% (39/425).
ESBL-producing E. coli episodes were significantly associated with HCA-BUO
episodes [14% (30/215) versus 4.3% (9/210); P = 0.001]. The highest non
susceptibility proportions corresponded to ciprofloxacin (97.4%),
amoxicillin/clavulanate (74.4%), co-trimoxazole (69.2%) and tobramycin (61.5%).
Of the 39 ESBL-producing E. coli isolates, 34 produced CTX-M enzymes (21 CTX-M
15, 11 CTX-M-14 and 2 CTX-M-1). Fifteen STs were identified, the B2-ST131 clone
being the most prevalent (54%; 21/39). All ST131 isolates were ExPEC and had the
highest virulence scores, but they showed less diversity in virulence profiles
than other STs. The H30Rx subclone accounted for most ST131 isolates (20/21), co
produced CTX-M-15 (20/20) and OXA-1 (19/20) enzymes and was associated with HCA
episodes (16/20). CONCLUSIONS: The CTX-M-15-ST131-H30Rx subclone is a relevant
MDR pathogen causing BUO, mainly HCA episodes. The dominance of this subclone
with comparatively less diversity of virulence profiles reflects the spread of a
successful and MDR ESBL ST131 lineage in Spain.
PMID- 27494833
TI - An orientation to wellness for new faculty of medicine members: meeting a need in
faculty development.
AB - OBJECTIVES: To evaluate the format, content, and effectiveness of a newly
developed orientation to wellness workshop, and to explore participants' overall
perceptions. METHODS: This was a mixed methods study. Participants consisted of
47 new faculty of medicine members who attended one of the four workshops held
between 2011 and 2013. Questionnaires were used to evaluate workshop
characteristics (10 survey items; response scale 1=unacceptable to
7=outstanding), intention to change behavior (yes/no), and retrospective pre/post
workshop self-efficacy (4 survey items; response scale 1=no confidence to
6=absolute confidence). Mean scores and standard deviations were calculated for
the workshop characteristics. Pre/post workshop self-efficacy scores were
compared using a Wilcoxon signed-rank test. Participants' written qualitative
feedback was coded using an inductive strategy to identify themes. RESULTS: There
was strong support for the workshop characteristics with mean scores entirely
above 6.00 (N=42). Thirty-one of 34 respondents (91%) expressed intention to
change their behavior as a result of participating in the workshop. The post
workshop self-efficacy scores (N=38 respondents) increased significantly for all
four items (p<0.0001) compared to pre workshop ratings. Participants perceived
the key workshop elements as the evidence-based content relevant to academic
physicians, incorporation of practical tips and strategies, and an atmosphere
conducive to discussion and experience sharing. CONCLUSIONS: Participants
welcomed wellness as a focus of faculty development. Enhancing instruction around
wellness has the potential to contribute positively to the professional
competency and overall functioning of faculty of medicine members.
PMID- 27494834
TI - GSK3beta inactivation promotes the oncogenic functions of EZH2 and enhances
methylation of H3K27 in human breast cancers.
AB - During the process of tumorigenesis, inactivation of tumor suppressors is a
critical step. EZH2, a histone methyltransferase, promotes cell growth and
migration through catalyzing trimethylation of histone H3 at Lys 27 (H3K27me3)
and plays an important role in tumorigenesis. Its expression can be controlled by
phosphorylation. However, the regulation of EZH2 activity by tumor suppressor
kinase is not well understood. In this study, we show that glycogen synthase
kinase 3 beta (GSK3beta) negatively regulates H3K27 trimethylation. We also
validate that GSKbeta physically interacts with EZH2, and their interaction
occurs in the cytosol. GSK3beta phosphorylates EZH2 at Ser363 and Thr367 in
vitro, and activating GSK3beta upregulates Thr367 phosphorylationin vivo. Cells
expressing GSK3beta-non-phosphorylatable mutant EZH2 have higher H3K27
trimethylation and enhanced ability of cell migration and anchorage-independent
growth. Inactivation of GSK3beta as measured by its phosphorylation at Ser9 is
positively correlated with higher level of H3K27 trimethylation in tumor tissues
from breast cancer patients. Our study indicated that GSK3beta phosphorylates
EZH2 at Ser363 and Thr367, resulting in reduced H3K27 trimethylation and
biological activity of EZH2 in breast cancer.
PMID- 27494835
TI - DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically
kill malignant melanoma cells in vivo.
AB - We combined chemo- and immunotherapies by constructing dual therapeutic function
immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody
(DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5
mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by
evaluating distribution in tumor-bearing nude mice using a real-time imaging
system. Therapeutic efficacy was assessed in terms of its effect on tumor volume,
survival time, histomorphology, microvessel density (MVD), and apoptotic index
(AI). Systemic toxicity was evaluated by measuring white blood cells (WBC)
counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In
vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the
accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor
growth more effectively than DTIC or DR5 mAb alone, indicating that combining
DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic
effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of
DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into
normal tissue and thus decreases toxic side effects. These results demonstrate
that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the
potential to improve the efficacy and specificity of melanoma treatment.
PMID- 27494836
TI - Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell
malignancies.
AB - Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to
treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and
dismal patient outlook. Despite the fact that PTCLs comprise the majority of T
cell malignancies, the standard of care is poorly established. Chimeric antigen
receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective
curative option and this extends promise into treating T-cell malignancies.
Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly
and uniformly expressed in many PTCL malignancies, with expression specific to
the hematological compartment thus making it an attractive target for CAR design.
We engineered a robust 3rd generation anti-CD3 CAR construct (CD3CAR) into an NK
cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently
lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells
lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and
suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival.
In this study, we present the CAR directed targeting of a novel target - CD3
using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and
potential for new therapeutic approaches that could improve the current standard
of care for PTCLs.
PMID- 27494837
TI - Loss of NEDD4 contributes to RTP801 elevation and neuron toxicity: implications
for Parkinson's disease.
AB - Parkinson's disease (PD) is a disorder characterized by the degeneration of
certain neuronal populations in the central and peripheral nervous system. One of
the hallmarks of the disease is the toxic accumulation of proteins within
susceptible neurons due to major impairment in the degradation/clearance protein
systems.RTP801 is a pro-apoptotic protein that is sufficient and necessary to
induce neuronal death in cellular and animal models of PD. RTP801 is also
upregulated in sporadic and parkin mutant PD brains. Here, we report the role of
NEDD4, an E3 ligase involved in alpha-synuclein degradation and PD pathogenesis,
in the regulation of RTP801 protein levels and toxicity. NEDD4 polyubiquitinates
RTP801 in a cell-free system and in cellular cultures, and they interact
physically. NEDD4 conjugates K63-ubiquitin chains to RTP801 and targets it for
degradation. NEDD4 regulates RTP801 protein levels in both cultured cells and in
the brain tissue. NEDD4 levels are diminished in nigral neurons from human PD
brains. Interestingly, neurotoxin 6-OHDA decreases dramatically NEDD4 protein
expression but elevates RTP801 protein levels. Moreover, NEDD4 protects neuronal
PC12 cells from both 6-OHDA and RTP801-induced toxicity. In primary cortical
neurons, NEDD4 knockdown toxicity is mediated by RTP801 since the double
knockdown of RTP801 and NEDD4 abrogates the loss of phospho Ser473-Akt and the
appearance of caspase-cleaved spectrin fragments.Thus, NEDD4 ligase regulates
RTP801 and is sensitive to PD-associated oxidative stress. This suggests that
NEDD4 loss of function in PD could contribute importantly into neuronal death by
elevating RTP801.
PMID- 27494838
TI - EGFR-targeted therapy results in dramatic early lung tumor regression accompanied
by imaging response and immune infiltration in EGFR mutant transgenic mouse
models.
AB - Lung adenocarcinoma patients harboring kinase domain mutations in Epidermal
growth factor receptor (EGFR) have significant clinical benefit from EGFR
targeted tyrosine kinase inhibitors (TKIs). Although a majority of patients
experience clinical symptomatic benefit immediately, an objective response can
only be demonstrated after 6-8 weeks of treatment. Evaluation of patient response
by imaging shows that 30-40% of patients do not respond due to intrinsic
resistance to these TKIs. We investigated immediate-early effects of EGFR-TKI
treatment in mutant EGFR-driven transgenic mouse models by FDG-PET and MRI and
correlated the effects on the tumor and the tumor microenvironment. Within 24
hours of erlotinib treatment we saw approximately 65% tumor regression in mice
with TKI-sensitive EGFRL858R lung adenocarcinoma. However, mice with
EGFRL858R/T790M-driven tumors did not respond to either erlotinib or afatinib
monotherapy, but did show a significant tumor response to afatinib-cetuximab
combination treatment. The imaging responses correlated with the inhibition of
downstream EGFR signaling, increased apoptosis, and decreased proliferation in
the tumor tissues. In EGFRL858R-driven tumors, we saw a significant increase in
CD45+ leukocytes, NK cells, dendritic cells, macrophages and lymphocytes,
particularly CD8+ T cells. In response to erlotinib, these dendritic cells and
macrophages had significantly higher MHC class II expression, indicating
increased antigen-presenting capabilities. Together, results of our study provide
novel insight into the immediate-early therapeutic response to EGFR TKIs in vivo.
PMID- 27494839
TI - DeltaNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis.
AB - P63 is a transcription factor belonging to the family of p53, essential for the
development and differentiation of epithelia. In recent years, it has become
clear that altered expression of the different isoforms of this gene can play an
important role in carcinogenesis. The p63 gene encodes for two main isoforms
known as TA and DeltaN p63 with different functions. The role of these different
isoforms in sustaining tumor progression and metastatic spreading however has not
entirely been clarified. Here we show that breast cancer initiating cells express
DeltaNp63 isoform that supports a more mesenchymal phenotype associated with a
higher tumorigenic and metastatic potential. On the contrary, the majority of
cells within the tumor appears to express predominantly TAp63 isoform. While
DeltaNp63 exerts its effects by regulating a PI3K/CD44v6 pathway, TAp63 modulates
this pathway in an opposite fashion. As a result, tumorigenicity and invasive
capacity of breast cancer cells is a balance of the two isoforms. Finally, we
found that tumor microenvironmental cytokines significantly contribute to the
establishment of breast cancer cell phenotype by positively regulating DeltaNp63
and CD44v6 expression.
PMID- 27494840
TI - Impaired 53BP1/RIF1 DSB mediated end-protection stimulates CtIP-dependent end
resection and switches the repair to PARP1-dependent end joining in G1.
AB - End processing at DNA double strand breaks (DSB) is a decisive step in repair
pathway selection. Here, we investigated the role of 53BP1/RIF1 in limiting
BRCA1/CtIP-mediated end resection to control DSB repair pathway choice. ATM
orchestrates this process through 53BP1 phosphorylation to promote RIF1
recruitment. As cells enter S/G2-phase, end resection is activated, which
displaces pATM from DSB sites and diminishes 53BP1 phosphorylation and RIF1
recruitment. Consistently, the kinetics of ATM and 53BP1 phosphorylation in S/G2
phase concur. We show that defective 53BP1/RIF1-mediated DSB end-protection in G1
phase stimulates CtIP/MRE11-dependent end-resection, which requires Polo-like
kinase 3. This end resection activity in G1 was shown to produce only short
tracks of ssDNA overhangs, as evidenced by the findings that in 53BP1 depleted
cells, (i) RPA focus intensity was significantly lower in G1 compared to that in
S/G2 phase, and (ii) EXO1 knockdown did not alter either number or intensity of
RPA foci in G1 but significantly decreased the RPA focus intensity in S/G2 phase.
Importantly, we report that the observed DSB end resection in G1 phase inhibits
DNA-PK-dependent nonhomologous end joining but is not sufficient to stimulate HR.
Instead, it switches the repair to the alternative PARP1-dependent end joining
pathway.
PMID- 27494841
TI - Agonistic analogs of growth hormone releasing hormone (GHRH) promote wound
healing by stimulating the proliferation and survival of human dermal fibroblasts
through ERK and AKT pathways.
AB - Decreased or impaired proliferation capability of dermal fibroblasts interferes
with successful wound healing. Several growth factors tested failed to fully
restore the growth of fibroblasts, possibly due to their rapid degradation by
proteases. It is therefore critical to find new agents which have stimulatory
effects on fibroblasts while being highly resistant to degradation. In such a
scenario, the activities of two agonistic analogs of growth hormone releasing
hormone (GHRH), MR-409 and MR-502, were evaluated for their impact on
proliferation and survival of primary human dermal fibroblasts. In vitro, both
analogs significantly stimulated cell growth by more than 50%. Under serum
depletion induced stress, fibroblasts treated with MR-409 or MR-502 demonstrated
better survival rates than control. These effects can be inhibited by either
PD98059 or wortmannin. Signaling through MEK/ERK1/2 and PI3K/AKT in an IGF-1
receptor-independent manner is required. In vivo, MR-409 promoted wound closure.
Animals treated topically with MR-409 healed earlier than controls in a dose
dependent manner. Histologic examination revealed better wound contraction and
less fibrosis in treated groups. In conclusion, MR-409 is a potent mitogenic and
anti-apoptotic factor for primary human dermal fibroblasts. Its beneficial
effects on wound healing make it a promising agent for future development.
PMID- 27494842
TI - The photosensitizer verteporfin has light-independent anti-leukemic activity for
Ph-positive acute lymphoblastic leukemia and synergistically works with
dasatinib.
AB - Cell lines have been used for drug discovery as useful models of cancers;
however, they do not recapitulate cancers faithfully, particularly from the
viewpoints of microenvironmental independence. Patient-derived xenografts (PDX)
are established by the transfer of primary tumor cells directly from patients
into immunodeficient mice and can provide primary-like tumor cells of the amount
needed at the desired time. We developed a high-throughput drug screening system
using PDX cells and performed drug screening using the PDX cells of Philadelphia
chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). We established four
Ph+ ALL PDX mice and performed high-throughput screening of 3440 compounds using
leukemia cells from the PDX mice (PDX-cell screening). The profiles of drugs
selected by PDX-cell screening were markedly different from those by screening
using the Ph+ ALL cell line. We found that verteporfin, an FDA-approved drug,
exhibited strong PDX cell-specific cytotoxicity. In the validation assay, its
GI50 was 228 nM, 395 nM, and 538 nM in three PDX cells and 3.93 uM, 2.11 uM, and
5.61 uM in three cell lines. Although verteporfin is a photosensitizer activated
by photoirradiation, its cytotoxic effects were mediated by the light-independent
production of reactive oxygen species; therefore, its anti-leukemic effects were
also exerted in vivo without photoirradiation. Furthermore, it exhibited
synergistic effects with dasatinib, an ABL kinase inhibitor. These results
indicated the potential of verteporfin as a new anti-leukemic reagent.
PMID- 27494843
TI - Cardiac fibrosis in mouse expressing DsRed tetramers involves chronic autophagy
and proteasome degradation insufficiency.
AB - Proteinopathy in the heart which often manifests excessive misfolded/aggregated
proteins in cardiac myocytes can result in severe fibrosis and heart failure.
Here we developed a mouse model, which transgenically express tetrameric DsRed, a
red fluorescent protein (RFP), in an attempt to mimic the pathological mechanisms
ofcardiac fibrosis. Whilst DsRed is expressed and forms aggregation in most mouse
organs, certain pathological defects are specifically recapitulated in cardiac
muscle cells including mitochondria damages, aggresome-like residual bodies,
excessive ubiquitinated proteins, and the induction of autophagy. The
proteinopathy and cellular injuries caused by DsRed aggregates may be due to
impaired or overburdened ubiquitin-proteasome system and autophagy-lysosome
systems. We further identified that DsRed can be ubiquitinated and associated
with MuRF1, a muscle-specific E3 ligase. Concomitantly, an activation of NF
kappaB signaling and a strong TIMP1 induction were noted, suggesting that RFP
induced fibrosis was augmented by a skewed balance between TIMP1 and MMPs. Taken
together, our study highlights the molecular consequences of uncontrolled protein
aggregation leading to congestive heart failure, and provides novel insights into
fibrosis formation that can be exploited for improved therapy.
PMID- 27494844
TI - Dose-dependent genotype effects of BDNF Val66Met polymorphism on default mode
network in early stage Alzheimer's disease.
AB - In humans, brain-derived neurotrophic factor (BDNF) has been shown to play a
pivotal role in neurocognition, and its gene contains a functional polymorphism
(Val66Met) that may explain individual differences in brain volume and memory
related activity.In this study, we enrolled 186 Alzheimer's disease (AD) patients
who underwent 3D T1 magnetic resonance imaging, and explored the gray matter (GM)
structural covariance networks (SCN). The patients were divided into three groups
according to their genotype: Met/Met (n = 45), Val/Met (n = 86) and Val/Val (n =
55). Seed-based analysis was performed focusing on four SCN networks.
Neurobehavioral scores served as the major outcome factor.Only peak cluster
volumes of default mode medial temporal lobe network showed significant genotype
interactions, of which the interconnected peak clusters showed dose-dependent
genotype effects. There were also significant correlations between the cognitive
test scores and interconnected-cluster volumes, especially in the orbitofrontal
cortex.These findings support the hypothesis that BDNF rs6265 polymorphisms
modulate entorhinal cortex-interconnected clusters and the valine allele was
associated with stronger structural covariance patterns that determined the
cognitive outcomes.
PMID- 27494845
TI - Smac mimetic LCL161 overcomes protective ER stress induced by obatoclax,
synergistically causing cell death in multiple myeloma.
AB - Bcl2 and IAP families are anti-apoptotic proteins deregulated in multiple myeloma
(MM) cells. Pharmacological inhibition of each of these families has shown
significant activity only in subgroups of MM patients. Here, we have examined a
broad-spectrum Bcl2 family inhibitor Obatoclax (OBX) in combination with a Smac
mimetic LCL161 in MM cell lines and patient cells. LCL161/OBX combination induced
synergistic cytotoxicity and anti-proliferative effects on a broad range of human
MM cell lines. The cytotoxicity was mediated through inhibition of the IAPs,
activation of caspases and up regulation of the pro-apoptotic proteins Bid, Bim,
Puma and Noxa by the drug combination. In addition, we observed that OBX caused
ER stress and activated the Unfolded Protein Response (UPR) leading to drug
resistance. LCL161, however inhibited spliced Xbp-1, a pro-survival factor. In
addition, we observed that OBX increased GRP78 localization to the cell surface,
which then induced PI3K dependent Akt activation and resistance to cell death.
LCL161 was able to block OBX induced Akt activation contributing to synergistic
cell death. Our results support clinical evaluation of this combination strategy
in relapsed refractory MM patients.
PMID- 27494847
TI - Preoperative neutrophil-to-lymphocyte ratio and tumor-related factors to predict
lymph node metastasis in patients with pancreatic ductal adenocarcinoma (PDAC).
AB - As a poor prognosis indicator in patients with pancreatic ductal adenocarcinoma
(PDCA), lymph node (LN) metastasis is of great importance in treatment. Present
study was performed to evaluate the predictive value of preoperative neutrophil
to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and possible
clinical parameters on the LN metastasis in PDCA patients. A total of 159
operable patients with PDCA were enrolled in our study. The clinical utility of
NLR and other clinical parameters was evaluated by receiver operating
characteristic (ROC) curves. Overall survival analysis indicated that LN
metastasis is an independent prognostic factor. The logistic analysis was used to
determine the independent parameters associated with LN metastasis. Ideal cutoff
values for predicting LN metastasis are 2.12 for NLR and 130.96 for PLR according
to the ROC curve. Multivariate analyses indicate that NLR (HR 2.588; 95% CI 1.246
5.376; P = 0.011), CA125 (HR 6.348; 95% CI 2.056-19.594; P = 0.001) and CA19-9
(HR 2.738; 95% CI 1.151-6.515; P = 0.023) are associated significantly with LN
metastasis independently. Preoperative NLR, CA125 and CA19-9 are useful
biomarkers for the prediction of LN metastasis in PDCA patients.
PMID- 27494846
TI - ADAR1 is vital for B cell lineage development in the mouse bone marrow.
AB - Adenosine deaminase acting on RNA (ADAR) 1 is the master editor of the
transcriptome, catalyzing the conversion of adenosine to inosine (A-to-I). RNA
transcripts fold into a variety of secondary structures including long
intramolecular RNA duplexes that are the major substrate of ADAR1. Most A-to-I
editing sites occur within RNA duplexes formed by complementary pairing of
inverted retrotransposable elements interspersed within noncoding regions of
transcripts. This catalytic activity of ADAR1 most likely prevents the abnormal
activation of cytosolic nucleic acid sensors by self-dsRNAs. Homozygous
disruption of mouse Adar is embryonic lethal due to a toxic type-I interferons
response and correspondingly biallelic missense mutations in human ADAR1 cause a
severe congenital interferonopathy. Here, we report that Cd19-Cre-mediated Adar
gene ablation in the mouse causes a significant defect in the final stages of B
cell development with an almost complete absence of newly formed immature and
CD23+ mature recirculating B cells in the BM. Adar ablation in pre-B cells
induced upregulation of typical interferon-stimulated genes (ISGs) and apoptosis
upon further maturation. ADAR1 deficiency also inhibited the in vitro, IL-7
mediated, differentiation of BM-derived B cell precursors. In summary, ADAR1 is
required, non-redundantly, for normal B lymphopoiesis in the BM and peripheral
maintenance.
PMID- 27494848
TI - Metformin use improves survival of diabetic liver cancer patients: systematic
review and meta-analysis.
AB - Metformin has garnered considerable interest as a chemo-preventive and chemo
therapeutic agent given the increased risk of liver cancer among diabetic
patients. This work was performed to illustrate the association between metformin
use and survival of diabetic liver cancer patients. We conducted a comprehensive
literature search of PubMed, Web of Science, Embase, BIOSIS Previews, Cochrane
Library from inception to 12 May 2016. Meta-analyses were performed using Stata
(version 12.0), with hazard ratios (HRs) and corresponding 95% confidence
intervals (CIs) as effect measures. Eleven cohort studies involving 3452 liver
cancer patients fulfilled the inclusion criteria. Meta-analyses showed that
metformin use was associated with better survival (HR = 0.59; 95% CI, 0.42-0.83;
p = 0.002) of liver cancer patients, and the beneficial effect persisted (HR =
0.64; 95% CI, 0.42-0.97; p = 0.035) when the population was restricted to
diabetic liver cancer patients. After adjusting for age, etiology, index of tumor
severity and treatment of liver cancer, the association between metformin use and
better survival of liver cancer patients was stable, pooled HR ranged from 0.47
to 0.57. The results indicated that metformin use improved survival of diabetic
liver cancer patients. However, the results should be interpreted with caution
given the possibility of residual confounding. Further prospective studies are
still needed to confirm the prognostic benefit of metformin use.
PMID- 27494849
TI - Twist1-induced epithelial-mesenchymal transition according to microsatellite
instability status in colon cancer cells.
AB - Colorectal cancer (CRC) with microsatellite instability (MSI) may exhibit
impaired epithelial-mesenchymal transition (EMT), but little is known about the
underlying mechanisms of this phenomenon. In this study, we investigated the role
of Twist1 and its downstream signaling cascades in EMT induction according to MSI
status. To investigate the effects of Twist1 on EMT induction according to MSI
status, MSS LS513 and MSI LoVo colon cancer cell lines, which overexpress human
Twist1, were generated. Twist1-induced EMT and its downstream signaling pathways
were evaluated via in vitro and in vivo experiments. We found that Twist1 induced
EMT markers and stem cell-like characteristics via AKT signaling pathways. Twist1
induced activation of AKT and suppression of glycogen synthase kinase (GSK)
3beta, which resulted in the activation of beta-catenin, increasing CD44
expression. In addition, Twist1 activated the AKT-induced NF-kappaB pathway,
increasing CD44 and CD166 expression. Activation of both the AKT/GSK-3beta/beta
catenin and AKT/NF-kappaB pathways occurred in MSS LS513 cells, while only the
AKT/GSK-3beta/beta-catenin pathway was activated in MSI LoVo cells. In
conclusion, Twist1 induces stem cell-like characteristics in colon cancer cell
lines related to EMT via AKT signaling pathways, and those pathways depend on MSI
status.
PMID- 27494850
TI - The 3'UTR signature defines a highly metastatic subgroup of triple-negative
breast cancer.
AB - Triple-negative breast cancer (TNBC) is a highly heterogeneous disease with an
aggressive clinical course. Prognostic models are needed to chart potential
patient outcomes. To address this, we used alternative 3'UTR patterns to improve
postoperative risk stratification. We collected 327 publicly available
microarrays and generated the 3'UTR landscape based on expression ratios of
alternative 3'UTR. After initial feature filtering, we built a 17-3'UTR-based
classifier using an elastic net model. Time-dependent ROC comparisons and Kaplan
Meier analyses confirmed an outstanding discriminating power of our prognostic
model for TNBC patients. In the training cohort, 5-year event-free survival (EFS)
was 78.6% (95% CI 71.2-86.0) for the low-risk group, and 16.3% (95% CI 2.3-30.4)
for the high-risk group (log-rank p<0.0001; hazard ratio [HR] 8.29, 95% CI 4.78
14.4), In the validation set, 5-year EFS was 75.6% (95% CI 68.0-83.2) for the low
risk group, and 33.2% (95% CI 17.1-49.3) for the high-risk group (log-rank
p<0.0001; HR 3.17, 95% CI 1.66-5.42). In conclusion, the 17-3'UTR-based
classifier provides a superior prognostic performance for estimating disease
recurrence and metastasis in TNBC patients and it may permit personalized
management strategies.
PMID- 27494851
TI - Differential expression of cyclooxygenase-2 in metastatic melanoma affects
progression free survival.
AB - The possible correlation between cyclooxygenase-2 (COX-2) expression and disease
progression in melanoma is still a matter of debate. Analysis of COX-2 expression
in 45 lymph node melanoma metastases demonstrates a significant correlation
between the percent of expression and progression free survival (PFS). A positive
COX-2 expression >=10% (COX-2high), as opposite to a positive expression <=9%
(COX-2low), translated into a striking significant reduction of PFS of about 3
years. The reduction in PFS correlated neither with BRAFV600E nor with NRASQ61
expression in the analyzed samples. This concept was reinforced by the finding
that tumour development in COX-2-/- mice was almost blunted. Similarly,
inhibition of COX-2 protein expression in human melanoma cell lines, by using
siRNAs technology as well as selective inhibition of COX-2 activity by celecoxib,
reduced cellular proliferation and invasiveness. In conclusion we show that COX
2high is a negative prognostic factor in metastatic melanoma. Our study also
clarifies that the uncertainty about the role of COX-2 in metastatic malignant
melanoma, found in the current relevant literature, is probably due to the fact
that a threshold in COX-2 expression has to be reached in order to impact on
cancer malignancy. Our findings suggest that COX-2 expression may become an
useful diagnostic tool in defining melanoma malignancy as well as argue for a
possible therapeutic use of NSAID as add on therapy in selected cases.
PMID- 27494852
TI - PATZ1 expression correlates positively with BAX and negatively with BCL6 and
survival in human diffuse large B cell lymphomas.
AB - Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which
differ in both cellular origin and clinical behavior. Among the aggressive
malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the
most frequently observed. They are themselves clinically and molecularly
heterogeneous and have been further sub-divided in three sub-types according to
different cell of origin, mechanisms of oncogenesis and clinical outcome. Among
them, the germinal center B-cell-like (GCB) derives from the germinal center and
expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice
develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human
NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170
NHLs, we found that PATZ1 nuclear expression is down-regulated in follicular
lymphomas and DLBCLs. Moreover, consistent with our previous results showing a
PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1
nuclear expression significantly correlates with high BCL6 expression, mainly in
DLBCLs, and with low BAX expression, also considering separately follicular
lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival
in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin,
vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly
associated to a worst outcome and demonstrated an independent prognostic factor
in multivariate analysis, including known prognostic factors of DLBCL, IPI score
and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic
marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis
through inhibiting and enhancing transcription of BCL6 and BAX, respectively.
PMID- 27494853
TI - Met promotes the formation of double minute chromosomes induced by Sei-1 in NIH
3T3 murine fibroblasts.
AB - BACKGROUND: Sei-1 is an oncogene capable of inducing double minute chromosomes
(DMs) formation. DMs are hallmarks of amplification and contribute to
oncogenesis. However, the mechanism of Sei-1 inducing DMs formation remains
unelucidated. RESULTS: DMs formation significantly increased during serial
passage in vivo and gradually decreased following culture in vitro. micro nuclei
(MN) was found to be responsible for the reduction. Of the DMs-carrying genes,
Met was found to be markedly amplified, overexpressed and highly correlated with
DMs formation. Inhibition of Met signaling decreased the number of DMs and
reduced the amplification of the DMs-carrying genes. We identified a 3.57Mb DMs
representing the majority population, which consists of the 1.21 Mb AMP1 from
locus 6qA2 and the 2.36 Mb AMP2 from locus 6qA2-3. MATERIALS AND METHODS: We
employed NIH-3T3 cell line with Sei-1 overexpression to monitor and characterize
DMs in vivo and in vitro. Array comparative genome hybridization (aCGH) and
fluorescence in situ hybridization (FISH) were performed to reveal amplification
regions and DMs-carrying genes. Metaphase spread was prepared to count the DMs.
Western blot and Met inhibition rescue experiments were performed to examine for
involvement of altered Met signaling in Sei-1 induced DMs. Genomic walking and
PCR were adopted to reveal DMs structure. CONCLUSIONS: Met is an important
promotor of DMs formation.
PMID- 27494855
TI - Next generation multi-scale biophysical characterization of high precision cancer
particle radiotherapy using clinical proton, helium-, carbon- and oxygen ion
beams.
AB - The growing number of particle therapy facilities worldwide landmarks a novel era
of precision oncology. Implementation of robust biophysical readouts is urgently
needed to assess the efficacy of different radiation qualities. This is the first
report on biophysical evaluation of Monte Carlo simulated predictive models of
prescribed dose for four particle qualities i.e., proton, helium-, carbon- or
oxygen ions using raster-scanning technology and clinical therapy settings at
HIT. A high level of agreement was found between the in silico simulations, the
physical dosimetry and the clonogenic tumor cell survival. The cell fluorescence
ion track hybrid detector (Cell-Fit-HD) technology was employed to detect
particle traverse per cell nucleus. Across a panel of radiobiological surrogates
studied such as late ROS accumulation and apoptosis (caspase 3/7 activation), the
relative biological effectiveness (RBE) chiefly correlated with the radiation
species-specific spatio-temporal pattern of DNA double strand break (DSB)
formation and repair kinetic. The size and the number of residual nuclear gamma
H2AX foci increased as a function of linear energy transfer (LET) and RBE,
reminiscent of enhanced DNA-damage complexity and accumulation of non-repairable
DSB. These data confirm the high relevance of complex DSB formation as a central
determinant of cell fate and reliable biological surrogates for cell survival/
RBE. The multi-scale simulation, physical and radiobiological characterization of
novel clinical quality beams presented here constitutes a first step towards
development of high precision biologically individualized radiotherapy.
PMID- 27494857
TI - Visceral fat adipocytes from obese and colorectal cancer subjects exhibit
distinct secretory and omega6 polyunsaturated fatty acid profiles and deliver
immunosuppressive signals to innate immunity cells.
AB - Obesity is a low-grade chronic inflammatory state representing an important risk
factor for colorectal cancer (CRC). Adipocytes strongly contribute to
inflammation by producing inflammatory mediators. In this study we investigated
the role of human visceral fat adipocytes in regulating the functions of innate
immunity cells. Adipocyte-conditioned media (ACM) from obese (n = 14) and CRC
(lean, n = 14; obese, n = 13) subjects released higher levels of pro
inflammatory/immunoregulatory factors as compared to ACM from healthy lean
subjects (n = 13). Dendritic cells (DC), differentiated in the presence of ACM
from obese and CRC subjects, expressed elevated levels of the inhibitory
molecules PD-L1 and PD-L2, and showed a reduced IL-12/IL-10 ratio in response to
both TLR ligand- and gammadelta T lymphocyte-induced maturation. Furthermore, CRC
patient-derived ACM inhibited DC-mediated gammadelta T cell activation. The
immunosuppressive signals delivered by ACM from obese and CRC individuals were
associated with a pro-inflammatory secretory and omega6 polyunsaturated fatty
acid profile of adipocytes. Interestingly, STAT3 activation in adipocytes
correlated with dihomo-gammalinolenic acid content and was further induced by
arachidonic acid, which conversely down-modulated PPARgamma. These results
provide novel evidence for a cross-talk between human adipocytes and innate
immunity cells whose alteration in obesity and CRC may lead to immune
dysfunctions, thus setting the basis for cancer development.
PMID- 27494858
TI - Dichloroacetate potentiates tamoxifen-induced cell death in breast cancer cells
via downregulation of the epidermal growth factor receptor.
AB - Metabolic reprogramming in cancer cells has recently been recognized as an
essential hallmark of neoplasia. In this context, metabolic alterations represent
an attractive therapeutic target, and encouraging results with drugs targeting
various metabolic processes have been obtained in preclinical studies. Recently,
several studies have suggested that dichloroacetate (DCA), a specific pyruvate
dehydrogenase kinase inhibitor, may be a potential anticancer drug in a large
number of diverse tumors. However, the precise mechanism is not fully understood,
which is important for the use of DCA in cancer treatment. In the present study,
we found that DCA sensitized MCF7 breast cancer cells to tamoxifen-induced cell
death by decreasing epidermal growth factor receptor (EGFR) expression. The
downregulation of EGFR was caused by degradation of the protein. Furthermore, p38
mitogen-activated protein kinase played an important role in DCA/tamoxifen
induced EGFR degradation. Finally, DCA also promoted comparable tamoxifen-induced
cell death in tamoxifen-resistant MCF7 cells, which were established by long-term
treatment with tamoxifen. In summary, our results suggest that DCA is an
attractive potential drug that sensitizes cells to tamoxifen-induced cell death
and overcome tamoxifen resistance via downregulation of EGFR expression in breast
cancer cells.
PMID- 27494859
TI - MiRNA-22 inhibits oncogene galectin-1 in hepatocellular carcinoma.
AB - Hepatic stellate cells (HSCs) induce immune privilege and promote hepatocellular
carcinoma (HCC) by suppressing the immune system. On the other hand, galectin-1
and miRNA-22 (miR-22) are dysregulated in HCC and serve as prognostic indicators
for patients. In this study, therefore, we measured galectin-1 and miR-22
expression in HSCs isolated from HCC tissues (Ca-HSCs), and in normal liver
tissues (N-HSCs) as a control. We also investigated the apoptosis rate among T
cells and the production of cytokines (IFN-gamma and IL-10) in HSCs co-cultured
with T cells. And we used immunohistochemical staining to tested for correlation
between galectin-1 expression, CD3 expression and clinicopathological features in
162 HCC patients. Our results showed that galectin-1 expression was much higher
in Ca-HSCs than in N-HSCs. Overexpression of galectin-1 promoted HSC-induced T
cell apoptosis and cytokine production (IFN-gamma and IL-10), while miR-22
expression inhibited it. Galectin-1 expression correlated negatively with miR-22
expression in HSCs. High galectin-1 and low CD3 expression levels were associated
with poor prognosis in HCC patients. These results suggest that the
immunosuppressive microenvironment promoted by HSC-derived galectin-1 in HCC can
be inhibited by miR-22. Galectin-1 and miR-22 could potentially serve as
prognostic markers and therapeutic targets in HCC.
PMID- 27494860
TI - Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via
suppressing RET/Src signaling pathway.
AB - The Rearranged during transfection (RET) fusion gene is a newly identified
oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study
is to explore the biological functions of the gene in tumorigenesis and
metastasis in RET gene fusion-driven preclinical models. We also investigate the
anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-beta, c-Src
and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms
underlying. Our results suggested that KIF5B-RET fusion gene promoted cell
invasion and migration, which were probably mediated through Src signaling
pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but
also via inhibition of migration and invasion by suppressing RET/Src signaling
pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET
driven tumors.
PMID- 27494861
TI - Decreased fucosylated PSA as a urinary marker for high Gleason score prostate
cancer.
AB - Fucosylation is an important oligosaccharide modification associated with cancer
and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA)
levels could be used for the detection of high Gleason score prostate cancer.
Urine samples were collected from men with abnormal digital rectal examination
findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody
ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL)
and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of
urinary Fuc-PSA were significantly decreased in the men with prostate cancer
compared with the men whose biopsies were negative for cancer (P = 0.026 and P <
0.001, respectively). Both were also significantly associated with the Gleason
scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively).
Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA
PhoSL were independent predictors of high Gleason score prostate cancer. The area
under the receiver-operator characteristic curve (AUC) value for the prediction
of cancers of Gleason score >= 7 was 0.69 for urinary PSA-AAL and 0.72 for
urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for
PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA
level is a potential marker for the detection of high Gleason score prostate
cancer.
PMID- 27494862
TI - Destabilisation, aggregation, toxicity and cytosolic mislocalisation of
nucleophosmin regions associated with acute myeloid leukemia.
AB - Nucleophosmin (NPM1) is a multifunctional protein that is implicated in the
pathogenesis of several human malignancies. To gain insight into the role of
isolated fragments of NPM1 in its biological activities, we dissected the C
terminal domain (CTD) into its helical fragments. Here we focus the attention on
the third helix of the NPM1-CTD in its wild-type (H3 wt) and AML-mutated (H3 mutA
and H3 mutE) sequences. Conformational studies, by means of CD and NMR
spectroscopies, showed that the H3 wt peptide was partially endowed with an alpha
helical structure, but the AML-sequences exhibited a lower content of this
conformation, particularly the H3 mutA peptide. Thioflavin T assays showed that
the H3 mutE and the H3 mutA peptides displayed a significant aggregation
propensity that was confirmed by CD and DLS assays. In addition, we found that
the H3 mutE and H3 mutA peptides, unlike the H3 wt, were moderately and highly
toxic, respectively, when exposed to human neuroblastoma cells. Cellular
localization experiments confirmed that the mutated sequences hamper their
nucleolar accumulation, and more importantly, that the helical conformation of
the H3 region is crucial for such a localization.
PMID- 27494863
TI - Guttiferone K suppresses cell motility and metastasis of hepatocellular carcinoma
by restoring aberrantly reduced profilin 1.
AB - Hepatocellular carcinoma (HCC) is an aggressive malignancy and the 5-year
survival rate of advanced HCC is < 10%. Guttiferone K (GUTK) isolated from the
Garcinia genus inhibited HCC cells migration and invasion in vitro and metastasis
in vivo without apparent toxicity. Proteomic analysis revealed that actin-binding
protein profilin 1 (PFN1) was markedly increased in the presence of GUTK. Over
expression of PFN1 mimicked the effect of GUTK on HCC cell motility and
metastasis. The effect of GUTK on cell motility was diminished when PFN1 was over
expressed or silenced. Over-expression of PFN1 or incubation with GUTK decreased
F-actin levels and the expression of proteins involved in actin nucleation,
branching and polymerization. Moreover, a reduction of PFN1 protein levels was
common in advanced human HCC and associated with poor survival rate. In
conclusion, GUTK effectively suppresses the motility and metastasis of HCC cells
mainly by restoration of aberrantly reduced PFN1 protein expression.
PMID- 27494865
TI - Lin28A activates androgen receptor via regulation of c-myc and promotes
malignancy of ER-/Her2+ breast cancer.
AB - Having previously demonstrated the co-expression status of the Lin28A and
androgen receptor (AR) in ER-/Her2+ breast cancer, we tested the hypothesis that
Lin28A can activate AR and promotes growth of ER-/Her2+ breast cancer. The
expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid
were transfected into ER-/Her2+ breast cancer cells. Chromatin immune
precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the
effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber
invasion assays, colony formation assays and flow cytometry analysis were
performed. ER-/Her2+ breast cancer cells which transfected with Lin28A siRNAs and
Lin28A plasmid were injected into nude mice, and tumorigenesis was monitored. Our
data showed that Lin28A can induced AR expression in ER-/Her2+ breast cancer
cells. ChIP analysis showed that Lin28A stimulates the recruitment of c-Myc to
the promoter of the AR gene. Lin28A enhanced growth ability, colonies ability,
cells proliferation activities, invasive ability and inhibited cells apoptosis of
ER-/Her2+ breast cancer cells. Lin28A high expression cells exhibited
significantly higher tumorigenic ability in vivo. Our study demonstrates that
Lin28A can activates androgen receptor via regulation of c-myc and promotes
malignancy of ER-/Her2+ breast cancer. Our findings underline a novel role for
Lin28A in breast cancer development and activation of the AR axis.
PMID- 27494866
TI - Whether regional lymph nodes evaluation should be equally required for both right
and left colon cancer.
AB - Despite the adequacy of nodal evaluation was gradually improved for colon cancer,
the disparity in nodal examination for right colon cancer (RCC) and left colon
cancer (LCC) still begs the question of whether 12 nodes is an appropriate
threshold for both RCC and LCC. From Surveillance, Epidemiology, and End-Results
(SEER) database, we identified 53897 RCC patients and 11822 LCC patients.
Compared with LCC patients, RCC patients examined more lymph nodes (18.7 vs
16.3), and more likely to examine >=12 nodes (P<0.001), whereas RCC patients
showed lower rates of node positivity (P<0.001). To balance the nodal disparity
between RCC and LCC, we revised the 12-node measure based on different tumor
locations. With the X-tile, we determined 15 as the optimal node number for RCC
and 11 for LCC. To validate the availability of this revised nodal evaluation,
the 5-year cancer specific survival (CSS) was calculated according to the optimal
node number in RCC and LCC patients, Cox's regression model were used to further
assess the prognostic value of this revised nodal evaluation. The results showed
that 5-year CSSs were significantly improved for RCC patients with >=15 lymph
nodes, and also for LCC patients with >=11 lymph nodes (P<0.001). This revised
nodal evaluation could also improve the rate of nodal positivity and long-term
survival in both RCC and LCC patients compared with 12-node measure. Therefore,
the lymph node examination should be discriminately evaluated for RCC and LCC,
instead of using 12-node measure to colon cancer as a whole.
PMID- 27494867
TI - Endoplasmic reticulum stress induces secretion of high-mobility group proteins
and is associated with tumor-infiltrating lymphocytes in triple-negative breast
cancer.
AB - BACKGROUND: Although the prognostic and predictive significance of tumor
infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) have been
shown, the cause of the TIL influx is unclear. Here, we investigated whether
extracellular secretion of HMGN1 is associated with TIL influx, as well as
increased endoplasmic reticulum stress (ERS), in human TNBC. METHODS: We reviewed
the slides of 767 patients with TNBC and evaluated the TIL levels. We also
assessed the expression of HMGs and several ERS-associated molecules using
immunohistochemical staining. Western blot analysis of human TNBC cell lines and
pharmacological ERS inducers was used to determine if HMGN1 migrates from the
nucleus to the extracellular space in response to ERS. RESULTS: On
immunohistochemical staining, either higher nuclear or cytoplasmic expression of
both HMGB1 and HMGN1 was significantly associated with ERS. TILs showed a
positive correlation with the cytoplasmic expression of the HMGs. Western blot
analysis of TNBC cell lines showed that ERS induction resulted in the secretion
of HMG proteins. CONCLUSIONS: This is the first study to elucidate the
associations among ERS, secretion of HMGs, and degree of TILs in TNBCs.
Understanding the mechanisms of TIL influx will help in the development of
effective immunotherapeutic agents for TNBC.
PMID- 27494868
TI - A lupus anti-DNA autoantibody mediates autocatalytic, targeted delivery of
nanoparticles to tumors.
AB - Strategies to target nanoparticles to tumors that rely on surface modification
with ligands that bind molecules overexpressed on cancer cells or the tumor
neovasculature suffer from a major limitation: with delivery of toxic agents the
amount of molecules available for targeting decreases with time; consequently,
the efficiency of nanoparticle delivery is reduced. To overcome this limitation,
here we propose an autocatalytic tumor-targeting mechanism based on targeting
extracellular DNA (exDNA). exDNA is enriched in the tumor microenviroment and
increases with treatment with cytotoxic agents, such as doxorubicin (DOX), due to
release of DNA by dying tumor cells. We tested this approach using poly(lactic-co
glycolic acid) (PLGA) nanoparticles surface-conjugated with fragments of 3E10
(3E10EN), a lupus anti-DNA autoantibody. We demonstrated that 3E10EN-conjugated
nanoparticles bound to DNA and preferentially localized to tumors in vivo. The
efficiency of tumor localization of 3E10EN-conjugated, DOX-loaded nanoparticles
increased with time and subsequent treatments, demonstrating an autocatalytic
effect. 3E10EN-conjugated DOX-loaded nanoparticles exhibited a significant anti
tumor effect that was superior to all controls. This work demonstrates the
promise of autocatalytic drug delivery mechanisms and establishes proof of
concept for a new anti-DNA autoantibody-based approach for enhancing delivery of
nanoparticles to tumors.
PMID- 27494869
TI - miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer
progression.
AB - The development and progression of CRC are regarded as a complicated network and
progressive event including genetic and/or epigenetic alterations. Recent
researches revealed that MicroRNAs are biomarkers and regulators of CRC
progression. Analyses of published microarray datasets revealed that miR-450b-5p
was highly up-regulated in CRC tissues. In addition, high expression of miR-450b
5p was significantly associated with KRAS mutation. However, the role of miR-450b
5p in the progression of CRC remains unknown. Here, we sought to validate the
expression of miR-450b-5p in CRC tissues and investigate the role and underlying
mechanism of miR-450b-5p in the progression of CRC. The results revealed that miR
450b-5p was up-regulated in CRC tissues, high expression level of miR-450b-5p was
positively associated with poor differentiation, advanced TNM classification and
poor prognosis. Moreover, miR-450b-5p was especially high in KRAS-mutated cell
lines and could be up-regulated by KRAS/AP-1 signaling. Functional validation
revealed that overexpression of miR-450b-5p promoted cell proliferation and tumor
growth while inhibited apoptosis of CRC cells. Furthermore, we demonstrated that
miR-450b-5p directly bound the 3'-UTRs of SFRP2 and SIAH1, and activated Wnt/beta
Catenin signaling. In conclusion, miR-450b-5p induced by oncogenic KRAS is
required for colorectal cancer progression. Collectively, our work helped to
understand the precise role of miR-450b-5p in the progression of CRC, and might
promote the development of new therapeutic strategies against CRC.
PMID- 27494870
TI - Novel antibody probes for the characterization of endosialin/TEM-1.
AB - Endosialin (Tumor Endothelial Marker-1 (TEM-1), CD248) is primarily expressed on
pericytes of tumor-associated microvasculature, tumor-associated stromal cells
and directly on tumors of mesenchymal origin, including sarcoma and melanoma.
While the function of endosialin/TEM-1 is incompletely understood, studies have
suggested a role in supporting tumor growth and invasion thus making it an
attractive therapeutic target. In an effort to further understand its role in
cancer, we previously developed a humanized anti-endosialin/TEM-1 monoclonal
antibody (mAb), called ontuxizumab (MORAb-004) for testing in preclinical and
clinical studies. We herein report on the generation of an extensive panel of
recombinant endosialin/TEM-1 protein extracellular domain (ECD) fragments and
novel mAbs against ECD motifs. The domain-specific epitopes were mapped against
ECD sub-domains to identify those that can detect distinct structural motifs and
can be potentially formatted as probes suitable for diagnostic and functional
studies. A number of mAbS were shown to cross-react with the murine and human
protein, potentially allowing their use in human animal models and corresponding
clinical trials. In addition, pairing of several mAbs supported their use in
immunoassays that can detect soluble endosialin/TEM-1 (sEND) in the serum of
healthy subjects and cancer patients.
PMID- 27494871
TI - Role of transarterial chemoembolization in relation with sorafenib for patients
with advanced hepatocellular carcinoma.
AB - BACKGROUND: Although sorafenib is considered standard therapy for advanced
hepatocellular carcinoma (HCC), actual treatments vary. We evaluated the effects
of different treatment strategies on overall survival. METHODS: A retrospective
study of sorafenib-treated patients with advanced HCC was conducted. The primary
outcome was overall survival. Prognostic factors were analyzed using multivariate
Cox-proportional hazards model. RESULTS: A total of 658 patients (mean age, 54.5
years; 83.3% male) were analyzed; 293, 129, and 236 patients were treated with
sorafenib, a combination therapy of sorafenib and transarterial chemoembolization
(TACE), and TACE followed by sorafenib, respectively. Overall, 51.2% of patients
treated under the combination strategy had portal vein invasion, whereas 89.9% of
patients receiving sorafenib monotherapy had distant metastasis. Median overall
survival durations were comparable (11.8 months for sorafenib, 16.2 months for
the combination therapy, and 13.5 months for TACE followed by sorafenib; P =
0.13). However, among portal vein invasion cases, combination (25.7 months, P =
0.002) and TACE followed by sorafenib (14.0 months, P = 0.030) treatments were
associated with longer overall survival duration compared with than sorafenib
monotherapy (5.5 months). In a multivariate model, sorafenib duration (hazard
ratio [HR], 0.96, P < 0.001) and TACE (HR, 0.24, P < 0.001) along with Child-Pugh
stage (HR, 1.83, P = 0.005) were associated with better survival. CONCLUSIONS: In
patients with portal vein invasion, TACE performed concurrently with or before
sorafenib administration is associated with better survival.
PMID- 27494872
TI - Role of micro-RNAs in drug resistance of multiple myeloma.
AB - While novel therapeutic approaches have profoundly improved survival of multiple
myeloma (MM) patients, drug resistance and treatment refractoriness still
persists. This obstacle highly demands thorough investigation into the root and
underlying molecular mechanisms to develop more effective strategies. The advent
of micro-RNAs (miRNAs) in the study of cancer biology and pathogenesis in recent
years has revolutionized therapy in this field and particularly opened new
windows to further understanding of tumor drug resistance. However; in spite of
the fact that miRNAs involvement in MM pathogenesis and progression has been
substantially evidenced, miRNA investigation in MM drug resistance is still in
its infancy. Our knowledge of the potential role of miRNAs in MM drug resistance
comes from few recent reports confirming that some miRNAs including miR-137/197,
miR-21 and miR-221/222 could negatively modulate drug sensitivity of MM cells.
Further continuous researches are required to exploit miRNAs to elucidate the
critical mechanisms controlling drug resistance in MM. In this review, we will
highlight the most recent observations on the role of miRNAs in MM drug
resistance. Moreover, approaches and insights into clinical application of miRNAs
to overcome MM drug resistance will be discussed.
PMID- 27494873
TI - Combinatorial therapeutic targeting of BMP2 and MEK-ERK pathways in NF1
associated malignant peripheral nerve sheath tumors.
AB - The clinical management of malignant peripheral nerve sheath tumors (MPNSTs) is
challenging not only due to its aggressive and invasive nature, but also limited
therapeutic options. Using gene expression profiling, our lab identified BMP2
SMAD1/5/8 pathway as a potential therapeutic target for treating MPNSTs. In this
study, we explored the therapeutic impact of targeting BMP2-SMAD1/5/8 pathway in
conjunction with RAS-MEK-ERK signaling, which is constitutively activated in
MPNSTs. Our results indicated that single agent treatment with LDN-193189, a BMP2
Type I receptor inhibitor, did not affect the growth and survival of MPNST cells
at biochemically relevant inhibitory concentrations. However, addition of a
MEK1/2 inhibitor, selumetinib, to LDN-193189-treated cells resulted in
significant inhibition of cell growth and induction of cell death. LDN-193189 at
biochemically effective concentrations significantly inhibited motility and
invasiveness of MPNST cells, and these effects were enhanced by the addition of
selumetinib. Overall, our results advocate for a combinatorial therapeutic
approach for MPNSTs that not only targets the growth and survival via inhibition
of MEK1/2, but also its malignant spread by suppressing the activation of BMP2
SMAD1/5/8 pathway. Importantly, these studies were conducted in low-passage
patient-derived MPNST cells, allowing for an investigation of the effects of the
proposed drug treatments in a biologically-relevant context.
PMID- 27494874
TI - Clock gene Per2 as a controller of liver carcinogenesis.
AB - Environmental disruption of molecular clocks promoted liver carcinogenesis and
accelerated cancer progression in rodents. We investigated the specific role of
clock gene Period 2 (Per2) for liver carcinogenesis and clock-controlled cellular
proliferation, genomic instability and inflammation. We assessed liver
histopathology, and determined molecular and physiology circadian patterns in
mice on chronic diethylnitrosamine (DEN) exposure according to constitutive Per2
mutation. First, we found that Per2m/m liver displayed profound alterations in
proliferation gene expression, including c-Myc derepression, phase-advanced Wee1,
and arrhythmic Ccnb1 and K-ras mRNA expressions, as well as deregulated
inflammation, through arrhythmic liver IL-6 protein concentration, in the absence
of any DEN exposure. These changes could then make Per2m/m mice more prone to
subsequently develop liver cancers on DEN. Indeed, primary liver cancers were
nearly fourfold as frequent in Per2m/m mice as compared to wild-type (WT), 4
months after DEN exposure. The liver molecular clock was severely disrupted
throughout the whole carcinogenesis process, including the initiation stage, i.e.
within the initial 17 days on DEN. Per2m/m further exhibited increased c-Myc and
Ccnb1 mean 24h expressions, lack of P53 response, and arrhythmic ATM, Wee1 and
Ccnb1 expressions. DEN-induced tumor related inflammation was further promoted
through increased protein concentrations of liver IL-6 and TNF-alpha as compared
to WT during carcinogenesis initiation. Per2 mutation severely deregulated liver
gene or protein expressions related to three cancer hallmarks, including
uncontrolled proliferation, genomic instability, and tumor promoting
inflammation, and accelerated liver carcinogenesis several-fold. Clock gene Per2
acted here as a liver tumor suppressor from initiation to progression.
PMID- 27494875
TI - Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects
their functional activity.
AB - BACKGROUND: Regulatory and cytotoxic T cells are key players in the host's
anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+
cells to identify potential interactions. METHODS: In 202 patients 103 pre
radiochemotherapy biopsies and 153 post-radiochemotherapy tumour specimens of
advanced rectal cancer were available and an immunohistochemical double staining
of FoxP3+ and CD8+ tumour-infiltrating lymphocytes was performed to investigate
cell density and cell-to-cell distances. RESULTS: FoxP3+ cells decreased after
radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged.
High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was
associated with an improved overall survival. Cell-to-cell distances of randomly
distributed cells were simulated and compared to observed cell-to-cell distances.
Observed distances shorter than the simulated, random distances were hypothesized
to represent FoxP3+ cells actively interacting with CD8+ cells. Epithelial short
distances were associated with a favourable prognosis while the opposite was true
for the stromal compartment. CONCLUSION: The analysis of cell-to-cell distances
may offer a tool to predict outcome, maybe by identifying functionally active,
interacting infiltrating inflammatory cells in different tumour compartments.
PMID- 27494876
TI - Xanthine oxidoreductase is required for genotoxic stress-induced NKG2D ligand
expression and gemcitabine-mediated antitumor activity.
AB - MICA/B (the major histocompatibility antigen-related chain A and B) and Rae I are
stress-inducible ligands for the immune-receptor NKG2D. Mechanisms by which
genotoxic stress and DNA damage induce the expression of NKG2D ligands remain
incompletely understood. Here, we report that inhibition of xanthine
oxidoreductase (XOR) activity by allopurinol or inhibition of XOR expression by
gene knockdown abrogated genotoxic stress-induced expression of MICA/B and Rae I
in three tumor cell lines. XOR knockdown also blocked gemcitabine-mediated
antitumor activity in an orthotopic syngeneic mouse model of breast cancer. As a
rate-limiting enzyme in the purine catabolic pathway, XOR generates two end
products, uric acid and reactive oxygen species (ROS). ROS scavenging had an
insignificant effect on genotoxic drug-induced MICA/B expression but modestly
inhibited radiation-induced MICA/B expression. Exogenous uric acid (in the form
of monosodium urate) induced MICA/B expression by activating the MAP kinase
pathway. Allopurinol blocked genotoxic stress-induced MAP kinase activation. Our
study provides mechanistic insights into genotoxic stress-induced activation of
the MAP kinase pathway and suggests that XOR is required for genotoxic stress
induced NKG2D ligand expression and gemcitabine-mediated antitumor activity.
PMID- 27494877
TI - FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT
dependent positive feedback loop.
AB - Gefitinib resistance remains a major problem in the treatment of lung
adenocarcinoma. However, the molecular mechanisms of gefitinib resistance are not
fully understood. In this study, we characterized the critical role of
transcription factor Forkhead box protein M1 (FOXM1) in gefitinib resistance of
lung adenocarcinoma cells. In vitro drug sensitivity assays demonstrated that
FOXM1 inhibition sensitized PC9/GR and HCC827/GR cells to gefitinib, whereas
FOXM1 overexpression enhanced PC9 and HCC827 cell resistance to gefitinib.
Increased FOXM1 resulted in the upregulation of hepatocyte growth factor receptor
(MET), which led to activation of the protein kinase B (AKT) pathway, whereas
knockdown of FOXM1 did the opposite. FOXM1 bound directly to the MET promoter
regions and regulated the promoter activities and the expression of MET at the
transcriptional level. Moreover, MET/AKT pathway upregulated the expression of
FOXM1 in lung adenocarcinoma cells. Inhibition of pAKT by LY294002 or inhibition
of pMET by PHA-665752 significantly inhibited the expression of FOXM1 in lung
adenocarcinoma cells. Importantly, we further demonstrated that the expression
levels of FOXM1, pAKT and MET were significantly increased in lung adenocarcinoma
tissues relative to normal lung tissues, and these three biomarkers were
concomitantly overexpressed in lung adenocarcinoma tissues. Taken together, our
results indicate that FOXM1 promotes acquired resistance to gefitinib of lung
adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a
positive feedback loop to promote lung adenocarcinoma development.
PMID- 27494878
TI - CD24 promoted cancer cell angiogenesis via Hsp90-mediated STAT3/VEGF signaling
pathway in colorectal cancer.
AB - CD24 is involved in tumor progression of various cancers, but the effects of CD24
on tumor angiogenesis in colorectal cancer are still unknown. We aimed to
investigate the underlying mechanism and role of CD24 on colorectal cancer (CRC)
angiogenesis. Our data showed that the microvessal density (MVD) was related to
the expression of CD24 in primary and metastasis CRC. Silencing of CD24 could
dramatically decrease human umbilical vein endothelial cell (HUVEC) migration,
invasion and tubule formation, but trivially affected cell proliferation. We also
mechanically showed that silencing CD24 could downregulate the expression of VEGF
via inhibiting the phosphorylation and translocation of STAT3. Moreover, Hsp90
was identified as the down-interaction protein of CD24 with co
immunoprecipitation assay and systematic mass spectrometry. Immunofluorescence
results showed Hsp90 partly co-localized with CD24 in CRC cell membrane and there
was a positive correlation between CD24 and Hsp90 expression in CRC tissues. We
gradually evidenced that Hsp90 modulated the stability and degradation of CD24 in
a proteasome-depended manner, and transferred the signal transmission from CD24
to STAT3. 17-AAG, a specific Hsp90, could abrogate the CD24 induce- HUVEC
migration, invasion and tubule formation in vitro and in vivo. Collectively, our
results suggested that CD24 induced CRC angiogenesis in Hsp90-dependent manner
and activated STAT3-mediated transcription of VEGF. We provided a new insight
into the regulation mechanism of tumor angiogenesis by exploring the role of CD24
in angiogenesis.
PMID- 27494879
TI - Epigenetic activation of LY6K predicts the presence of metastasis and poor
prognosis in breast carcinoma.
AB - The role of lymphocyte antigen 6 complex, locus K (LY6K) in breast cancer has
been studied, whereas the epigenetic control of LY6K transcription is not fully
understood. Here, we report that breast cancer patients with increased LY6K
expression had shorter disease-free and overall survival than the patients with
low levels of LY6K by multivariate analysis. LY6K also was upregulated in breast
cancer patients with distant metastases than those without distant metastases,
downregulating E-cadherin expression. Furthermore, xenograft tumor volumes from
LY6K knockdown nude mice were reduced than those of mice treated with control
lentivirus. Interestingly, LY6K has a CpG island (CGI) around the transcription
start site and non-CGI in its promoter, called a CGI shore. LY6K expression was
inversely correlated with methylation in not only CGI but CGI shore, which are
associated with histone modifications. Additionally, LY6K methylation was
increased by the PAX3 transcription factor due to the SNP242 mutation in LY6K CGI
shore. Taken together, breast cancer risk and metastasis were significantly
associated with not only LY6K expression, but also methylation of CGI shore which
induced by SNP242 mutation. Our results suggest that an understanding epigenetic
mechanism of the LY6K gene may be useful to diagnose carcinogenic risk and
predict outcomes of patients with metastatic breast cancer.
PMID- 27494880
TI - Predicting the cell death responsiveness and sensitization of glioma cells to
TRAIL and temozolomide.
AB - Genotoxic chemotherapy with temozolomide (TMZ) is a mainstay of treatment for
glioblastoma (GBM); however, at best, TMZ provides only modest survival benefit
to a subset of patients. Recent insight into the heterogeneous nature of GBM
suggests a more personalized approach to treatment may be necessary to overcome
cancer drug resistance and improve patient care. These include novel therapies
that can be used both alone and with TMZ to selectively reactivate apoptosis
within malignant cells. For this approach to work, reliable molecular signatures
that can accurately predict treatment responsiveness need to be identified first.
Here, we describe the first proof-of-principle study that merges quantitative
protein-based analysis of apoptosis signaling networks with data- and knowledge
driven mathematical systems modeling to predict treatment responsiveness of GBM
cell lines to various apoptosis-inducing stimuli. These include monotherapies
with TMZ and TRAIL, which activate the intrinsic and extrinsic apoptosis
pathways, respectively, as well as combination therapies of TMZ+TRAIL. We also
successfully employed this approach to predict whether individual GBM cell lines
could be sensitized to TMZ or TRAIL via the selective targeting of Bcl-2/Bcl-xL
proteins with ABT-737. Our findings suggest that systems biology-based approaches
could assist in personalizing treatment decisions in GBM to optimize cell death
induction.
PMID- 27494881
TI - Expression of the p66Shc protein adaptor is regulated by the activator of
transcription STAT4 in normal and chronic lymphocytic leukemia B cells.
AB - p66Shc attenuates mitogenic, prosurvival and chemotactic signaling and promotes
apoptosis in lymphocytes. Consistently, p66Shc deficiency contributes to the
survival and trafficking abnormalities of chronic lymphocytic leukemia (CLL) B
cells. The mechanism of p66shc silencing in CLL B cells is methylation
independent, at variance with other cancer cell types. Here we identify STAT4 as
a novel transcriptional regulator of p66Shc in B cells. Chromatin
immunoprecipitation and reporter gene assays showed that STAT4 binds to and
activates the p66shc promoter. Silencing or overexpression of STAT4 resulted in a
co-modulation of p66Shc. IL-12-dependent STAT4 activation caused a coordinate
increase in STAT4 and p66Shc expression, which correlated with enhanced B cell
apoptosis. Treatment with the STAT4 inhibitor lisofylline reverted partly this
effect, suggesting that STAT4 phosphorylation is not essential for but enhances
p66shc transcription. Additionally, we demonstrate that CLL B lymphocytes have a
STAT4 expression defect which partly accounts for their p66Shc deficiency, as
supported by reconstitution experiments. Finally, we show that p66Shc
participates in a positive feedback loop to promote STAT4 expression. These
results provide new insights into the mechanism of p66Shc expression in B cells
and its defect in CLL, identifying the STAT4/IL-12 pathway as a potential
therapeutic target in this neoplasia.
PMID- 27494882
TI - Simultaneous targeting of Eph receptors in glioblastoma.
AB - Eph tyrosine kinase receptors are frequently overexpressed and functional in many
cancers, and they are attractive candidates for targeted therapy. Here, we
analyzed the expression of Eph receptor A3, one of the most up-regulated factors
in glioblastoma cells cultured under tumorsphere-forming conditions, together
with EphA2 and EphB2 receptors. EphA3 was overexpressed in up to 60% of
glioblastoma tumors tested, but not in normal brain. EphA3 was localized in
scattered areas of the tumor, the invasive ring, and niches near tumor vessels.
EphA3 co-localized with macrophage/leukocyte markers, suggesting EphA3 expression
on tumor-infiltrating cells of bone marrow origin. We took advantage of the fact
that ephrinA5 (eA5) is a ligand that binds EphA3, EphA2 and EphB2 receptors, and
used it to construct a novel targeted anti-glioblastoma cytotoxin. The eA5-based
cytotoxin potently and specifically killed glioblastoma cells with an IC50 of at
least 10-11 M. This and similar cytotoxins will simultaneously target different
compartments of glioblastoma tumors while mitigating tumor heterogeneity.
PMID- 27494883
TI - Combined cell surface carbonic anhydrase 9 and CD147 antigens enable high
efficiency capture of circulating tumor cells in clear cell renal cell carcinoma
patients.
AB - Circulating tumor cells (CTCs) have emerged as promising tools for noninvasive
cancer detection and prognosis. Most conventional approaches for capturing CTCs
use an EpCAM-based enrichment strategy, which does not work well in cancers that
show low or no expression of EpCAM, such as renal cell carcinoma (RCC). In this
study, we developed a new set of cell surface markers including CA9 and CD147 as
alternative CTC-capture antigens specifically designed for RCC patients. We
showed that the expression of both CA9 and CD147 was prevalent in a RCC patient
cohort (n=70) by immunohistochemical analysis, with both molecules in combination
covering 97.1% of cases. The NanoVelcro platform combined with CA9-/CD147-capture
antibodies demonstrated significantly higher efficiency for capturing both CTC
mimicking renal cancer cells and RCC CTCs in peripheral blood, compared to the
conventional EpCAM-based method. Using immunofluorescence cytological validation
at the single-cell level, we were able to identify bona fide CTCs in RCC patient
blood following the well-accepted criteria in our CTC-capture system. We further
demonstrated a significant association of CTC numbers as well as the CTC
expression status of Vimentin, a mesenchymal marker, with disease progression,
including pathologic features and clinical staging. These results provide new
insights into developing novel, effective targets/approaches for capturing CTCs,
making CTCs a valuable tool for improved cancer detection, prognosis and
treatment in RCC.
PMID- 27494885
TI - Bromodomain inhibitor OTX015 (MK-8628) combined with targeted agents shows strong
in vivo antitumor activity in lymphoma.
AB - The bromodomain inhibitor OTX015 (MK-8628) has shown anti-lymphoma activity as a
single agent in both the preclinical and clinical settings, as well as in vitro
synergism with several anticancer agents. Here, we report in vivo data for OTX015
in combination with the histone deacetylase inhibitor vorinostat, the Bruton's
tyrosine kinase inhibitor ibrutinib, the anti-CD20 monoclonal antibody rituximab,
and the mTOR inhibitor everolimus in a diffuse large B cell lymphoma model. The
antitumor effect of OTX015-containing combinations in SU-DHL-2 xenografts in mice
was much stronger than the activity of the corresponding single agents with
almost complete tumor eradication for all four combinations. Pharmacokinetic
analyses showed similar OTX015 levels in plasma and tumor samples of
approximately 1.5 MUM, which is equivalent to the concentration showing strong in
vitro activity. For all four combinations, mean terminal levels of the
bromodomain inhibitor differed from those in mice exposed to single agent OTX015,
indicating a need for thorough pharmacokinetic investigations in phase I
combination studies. In conclusion, our results provide a strong rationale to
explore OTX015-containing combinations in the clinical lymphoma setting.
PMID- 27494886
TI - Healthy CD4+ T lymphocytes are not affected by targeted therapies against the
PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia.
AB - An attractive molecular target for novel anti-cancer therapies is the
phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
pathway which is commonly deregulated in many types of cancer. Nevertheless, the
effects of PI3K/Akt/mTOR inhibitors on T lymphocytes, a key component of immune
responses, have been seldom explored. In this study we investigated the effects
on human CD4+ T-cells of a panel of PI3K/Akt/mTOR inhibitors: BGT226, Torin-2, MK
2206, and ZSTK474. We also assessed their efficacy against two acute leukemia T
cell lines. T lymphocytes were stimulated with phytohemagglutinin. Inhibitor
effects on cell cycle and apoptosis were analyzed by flow cytometry, while
cytotoxicity was assessed by MTT assays. In addition, the activation status of
the pathway as well as induction of autophagy were analyzed by Western blotting.
Quiescent healthy T lymphocytes were unaffected by the drugs whereas mitogen
stimulated lymphocytes as well as leukemic cell lines displayed a cell cycle
block, caspase-dependent apoptosis, and dephosphorylation of key components of
the signaling pathway. Autophagy was also induced in proliferating lymphocytes
and in JURKAT and MOLT-4 cell lines. When autophagy was inhibited by 3
methyladenine or Bafilomycin A1, drug cytotoxicity was increased, indicating that
autophagy is a protective mechanism. Therefore, our findings suggest that
PI3K/Akt/mTOR inhibitors preserve lymphocyte viability. This is a valuable result
to be taken into account when selecting drugs for targeted cancer therapy in
order to minimize detrimental effects on immune function.
PMID- 27494887
TI - Ablation of human telomerase reverse transcriptase (hTERT) induces cellular
senescence in gastric cancer through a galectin-3 dependent mechanism.
AB - The human Telomerase Reverse Transcriptase (hTERT) gene encodes a rate-limiting
catalytic subunit of telomerase that maintains genomic integrity. Suppression of
hTERT expression could induce cellular senescence and is considered a potent
approach for gastric cancer therapy. However, control of hTERT expression and
function remains poorly understood in gastric cancer. In this study, we
demonstrated that high expression levels of hTERT in malignant tissues are
correlated with poor survival probability in gastric cancer patients. Knockdown
of hTERT expression retarded cell proliferation and cellular senescence, which
was confirmed by increased protein expression levels of p21cip1 and p27kip1, and
decreased phosphorylation of Rb. In contrast, overexpression of hTERT increased
cell proliferation and decreased cellular senescence. Remarkably, the down
regulation of hTERT expression was detected in lgals3-/- mouse embryo fibroblasts
(MEFs). Knockdown of galectin-3 decreased the expression of hTERT in gastric
cancer cells. Galectin-3 ablation-induced cellular senescence was rescued by
concomitant overexpression of hTERT. hTERT ablation-induced cellular senescence
and p21cip1 and p27kip1 expression was rescued by concomitant overexpression of
galectin-3. The size of tumor burdens was increased in hTERT-overexpressed
gastric cancer cells xenografted mice, whereas it was repressed by concomitant
depletion of galectin-3. Additionally, we determined that the N-terminal domain
of galectin-3 directly interacted with hTERT. The telomeric activity of hTERT was
also decreased by galectin-3 ablation. Taken together, ablation of hTERT induces
cellular senescence and inhibits the growth of gastric cancer cells, suggesting
that it could be a potent target in gastric cancer therapy. We also propose that
galectin-3 is an important regulator of hTERT expression and telomeric activity
in gastric tumorigenesis.
PMID- 27494889
TI - Stathmin overexpression is associated with growth, invasion and metastasis of
lung adenocarcinoma.
AB - Stathmin has been investigated as a tumor biomarker because it appear to be
associated with tumorigenesis; however, the effect of stathmin in lung
adenocarcinoma (LAC) remains poorly understood. The purpose of this study was to
examine the expression of stathmin in lung adenocarcinoma, and to disclose the
relationship between them. The expression of stathmin was examined by RT-PCR, IHC
and Western blot. Furthermore, small interfering RNA (shRNA)-mediated silencing
of stathmin was employed in LAC cells to investigate cell proliferation, invasion
and apoptosis. In this study, we showed that overexpression of stathmin was
significantly associated with poorly differentiated, lymph node metastasis and
advance TNM stages of lung adenocarcinoma. And silencing of stathmin expression
inhibited the proliferation, migration and invasion of lung adenocarcinoma PC-9
cells, and retarded the growth of PC-9 cells xenografts in nude mice.
Additionally, the anticarcinogenic efficacy of stathmin silencing might be
involved in P38 and MMP2 signaling pathways. In conclusion, these results showed
that stathmin expression was significantly up-regulated in LAC, which may act as
a biomarker for LAC. Furthermore, silence of stathmin inhibiting LAC cell growth
indicated that stathmin may be a promising molecular target for LAC therapy.
PMID- 27494888
TI - The trans-membrane domain of Bcl-2alpha, but not its hydrophobic cleft, is a
critical determinant for efficient IP3 receptor inhibition.
AB - The anti-apoptotic Bcl-2 protein is emerging as an efficient inhibitor of IP3R
function, contributing to its oncogenic properties. Yet, the underlying molecular
mechanisms remain not fully understood. Using mutations or pharmacological
inhibition to antagonize Bcl-2's hydrophobic cleft, we excluded this functional
domain as responsible for Bcl-2-mediated IP3Rs inhibition. In contrast, the
deletion of the C-terminus, containing the trans-membrane domain, which is only
present in Bcl-2alpha, but not in Bcl-2beta, led to impaired inhibition of IP3R
mediated Ca2+ release and staurosporine-induced apoptosis. Strikingly, the trans
membrane domain was sufficient for IP3R binding and inhibition. We therefore
propose a novel model, in which the Bcl-2's C-terminus serves as a functional
anchor, which beyond mere ER-membrane targeting, underlies efficient IP3R
inhibition by (i) positioning the BH4 domain in the close proximity of its
binding site on IP3R, thus facilitating their interaction; (ii) inhibiting IP3R
channel openings through a direct interaction with the C-terminal region of the
channel downstream of the channel-pore. Finally, since the hydrophobic cleft of
Bcl-2 was not involved in IP3R suppression, our findings indicate that ABT-199
does not interfere with IP3R regulation by Bcl-2 and its mechanism of action as a
cell-death therapeutic in cancer cells likely does not involve Ca2+ signaling.
PMID- 27494890
TI - Decreased TCL6 expression is associated with poor prognosis in patients with
clear cell renal cell carcinoma.
AB - One-third of clear cell renal cell carcinoma (ccRCC) patients present with
metastasis at the time of diagnosis. The prognosis of these patients is poor. To
identify potential prognostic biomarkers and therapeutic targets for ccRCC, we re
evaluated published long non-coding RNA (lncRNA) expression profiling data from
the Gene Expression Omnibus and ArrayExpress database. We found that five lncRNAs
were differentially expressed in ccRCC and adjacent tissues. These lncRNAs were
assessed in an independent cohort of 71 paired patient samples using real-time
PCR. Differences in expression of three of the lncRNAs (ENSG00000177133, TCL6,
and ENSG00000244020) were validated in this analysis. Kaplan-Meier analysis
indicated that low expression of ENSG00000177133 and TCL6 was associated with a
poor prognosis. Univariate and multivariate regression analyses demonstrated that
TCL6 but not ENSG00000177133 expression was an independent predictor of ccRCC
aggressiveness and had hazard ratios predictive of clinical outcome. TCL6
expression was negatively correlated with pTNM stage. Overexpression of TCL6 in
786-O and Caki-1 ccRCC cells decreased proliferation and increased apoptosis
compared to controls. Our results indicate that lncRNA expression is altered in
ccRCC and that decreased TCL6 expression may be an independent adverse prognostic
factor in ccRCC patients.
PMID- 27494891
TI - Analysis of the chemotherapeutic effects of a propadiene compound on malignant
ovarian cancer cells.
AB - Epithelial ovarian cancer is most lethal in female reproductive carcinomas owing
to the high chemoresistance and metastasis, so more efficient therapeutic agents
are terribly needed. A propadiene compound: 1-phenylpropadienyl phosphine oxide
(PHPO), was employed to test the chemotherapeutic efficacy against ovarian cancer
cell lines. MTT assay showed that PHPO displayed a much lower IC50 than cisplatin
and paclitaxel, while combination treatment of cells with PHPO + cisplatin
induced more apoptosis than with PHPO + paclitaxel or with cisplatin + paclitaxel
(p < 0.05). Animal assays demonstrated that subcutaneous tumor growth was highly
inhibited by PHPO + cisplatin, compared with that inhibited by PHPO or by
cisplatin treatment alone, indicating PHPO and cisplatin may have synergistic
effects against ovarian cancer growth. We also found that PHPO induced few side
effects on animals, compared with cisplatin. Mechanistic studies suggested that
treatment of cells with PHPO or with PHPO + cisplatin differentially inhibited
the PI3K/Akt, MAPK and ATM/Chk2 pathways, which consequently suppressed the anti
apoptotic factors Bcl-xL, Bcl-2 and XIAP, but activated the pro-apoptotic factors
Bad, Bax, p53, caspase 9, caspase 8, caspase 7 and PARP. Taken together, PHPO may
induce cell apoptosis through multiple signal pathways, especially when used
along with cisplatin. Therefore, PHPO may be explored as a prospective agent to
effectively treat ovarian cancer.
PMID- 27494892
TI - Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in
pancreatic neoplastic lesions.
AB - Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1
(SIRT1) is a lysine deacetylase of multiple targets including metabolic
regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless,
it is unclear if SIRT1 affects the development of neoplastic lesions and whether
metabolic gene expression is altered.To assess neoplastic lesion development,
mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a
KrasG12D mutant background (KC) that predisposes to the development of pancreatic
intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar
grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early
mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to
reduced proliferation. This was accompanied by reduced expression of proteins in
the glycolysis pathway, such as GLUT1 and GAPDH.The stimulatory effect of SIRT1
on proliferation and glycolysis gene expression was confirmed in a human PDAC
cell line. In resected PDAC samples, higher proliferation and expression of
glycolysis genes correlated with poor patient survival. SIRT1 expression per se
was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2
(CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival.These
findings open perspectives for novel targeted therapies in pancreatic cancer.
PMID- 27494893
TI - Blood concentration of cyclosporine during early post-transplant period may have
influence on the occurrence of chronic graft versus host disease in patients who
received allogeneic hematopoietic stem cell transplantation.
AB - INTRODUCTION: It has rarely been studied that how the blood level of CsA affect
the incidence of chronic GVHD after allogeneic hematopoietic stem cell
transplantation (allo-HSCT). METHODS: A total of 183 patients who underwent allo
HSCT from an HLA-matched or haplo matched family donors between 2006 and 2014
were reviewed. RESULTS: The average monthly CsA blood concentration (CsAavr
,ng/ml) was calculated in each patient: 0-1, 1-2, and 2-3 months after allo-HSCT.
CsAavr at the first month showed significant association with the occurrence of
moderate to severe cGVHD in multivariate analysis adjusted for gender, age, total
body irradiation, anti-thymocyte globulin, acute GVHD >= grade 2 and CsAavr
levels of other periods. The risk of cGVHD development was lowest in patients
with CsAavr of 200-250 ng/ml when compared to those with CsAavr of >= 250 or <
200 ng/ml (p=0.003). CONCLUSIONS: CsA level between 200 and 250 mg/ml during the
first month after transplantation was significantly associated with the decreased
risk of moderate to severe cGVHD.
PMID- 27494894
TI - Advanced interstitial chemotherapy combined with targeted treatment of malignant
glioma in rats by using drug-loaded nanofibrous membranes.
AB - Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary
brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded
three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and
cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and
an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and
combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically
implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic
studies and onto C6 glioma-bearing rats for estimating the therapeutic
efficacy.The chemotherapeutic agents were rapidly released from the 50:50 PLGA
nanofibres after implantation, followed by the release of combretastatin
(approximately 2 weeks later) from the 75:25 PLGA nanofibres. All drug
concentrations remained higher in brain tissues than in the blood for more than 8
weeks. The experimental results, including attenuated malignancy, retarded tumour
growth, and prolonged survival in tumour-bearing rats, demonstrated the efficacy
of the BICC/PLGA nanofibrous membranes. Furthermore, the efficacy of BIC/PLGA and
BICC/PLGA nanofibrous membranes was compared. The BICC/PLGA nanofibrous membranes
more efficiently retarded the tumour growth and attenuated the malignancy of C6
glioma-bearing rats. Moreover, the addition of combretastatin did not
significantly change the drug release behaviour of the BIC/PLGA nanofibrous
membranes. The present advanced and novel interstitial chemotherapy and targeted
treatment provide a potential strategy and regimen for treating GBM.
PMID- 27494895
TI - Hop derived flavonoid xanthohumol inhibits endothelial cell functions via AMPK
activation.
AB - Angiogenesis, a process characterized by the formation of new blood vessels from
pre-existing ones, is a crucial step in tumor growth and dissemination. Recently,
increased attention has been addressed to the ability of flavonoids to prevent
cancer by suppressing angiogenesis, strategy that we named "angioprevention".
Several natural compounds exert their anti-tumor properties by activating 5'
adenosine monophosphate-activated protein kinase (AMPK), a key regulator of
metabolism in cancer cells. Drugs with angiopreventive activities, in particular
metformin, regulate AMPK in endothelial cells. Here we investigated the
involvement of AMPK in the anti-angiogenic effects of xanthohumol (XN), the major
prenylated flavonoid of the hop plant, and mechanisms of action. The anti
angiogenic activity of XN was more potent than epigallocatechin-3-gallate (EGCG).
Treatment of endothelial cells with XN led to increased AMPK phosphorylation and
activity. Functional studies using biochemical approaches confirmed that AMPK
mediates XN anti-angiogenic activity. AMPK activation by XN was mediated by
CAMMKbeta, but not LKB1. Analysis of the downstream mechanisms showed that XN
induced AMPK activation reduced nitric oxide (NO) levels in endothelial cells by
decreasing eNOS phosphorylation. Finally, AKT pathway was inactivated by XN as
part of its anti-angiogenic activity, but independently from AMPK, suggesting
that these two signaling pathways proceed autonomously. Our study dissects the
molecular mechanism by which XN exerts its potent anti-angiogenic activity,
pointing out AMPK as a crucial signal transducer.
PMID- 27494896
TI - MicroRNA 10b promotes abnormal expression of the proto-oncogene c-Jun in
metastatic breast cancer cells.
AB - MicroRNAs have been shown to act as oncogenes or tumor suppressers via various
cellular pathways. Specifically, in breast cancer, upregulation of miR-10b is
positively associated with aggressiveness of tumors. However, the mechanism by
which miR-10b contributes to cell malignancy is largely unknown. Here we show
that at the receiving end of the miR-10b pathway is the proto-oncogene c-Jun, a
transcription factor that plays a critical role in stimulation of cell
proliferation and tumor progression. c-Jun is known to be translationally
activated by loss of cell contacts or restructuring of the cytoskeleton. A
comprehensive analysis of miRNA expression exhibited a significant increase in
miR-10b expression. This was supported by analysis of breast cancer cells, which
showed that loss of E-cadherin in metastatic cells is accompanied by elevation of
miR-10b and interestingly, by a marked increase in accumulation of c-Jun.
Silencing miR-10b in metastatic breast cancer cells leads to a decline in c-Jun
expression, whereas overexpression of miR-10b in HaCaT cells is sufficient to
elevate the accumulation of c-Jun. The increase in c-Jun protein accumulation in
metastatic cells is not accompanied by an increase in c-Jun mRNA and is not
dependent on MAPK activity. Knockdown and overexpression experiments revealed
that the increase is mediated by NF1 and RhoC, downstream targets of miR-10b that
affect cytoskeletal dynamics through the ROCK pathway. Overall, we show the
ability of miR-10b to activate the expression of c-Jun through RhoC and NF1,
which represents a novel pathway for promoting migration and invasion of human
cancer cells.
PMID- 27494897
TI - MicroRNA-891b is an independent prognostic factor of pancreatic cancer by
targeting Cbl-b to suppress the growth of pancreatic cancer cells.
AB - Growing evidence has revealed that microRNAs could regulate the proliferation of
pancreatic ductal adenocarcinoma (PDAC) cells and predict the prognosis of PDAC.
Here the comparative microRNA expression profiles of the good and poor prognosis
groups were performed by microRNA microarray. MicroRNA-891b (miR-891b) was
screened and validated to be a prognostic predictor of PDAC in the initial group
and further evaluated to be an independent predictor for the overall survival of
resectable PDACs in an independent cohort. By a series of cellular and animal
experiments, as well as clinical specimen analyses, miR-891b was confirmed to
target the Cbl-b gene, promot the expression of tumor suppressor p21 protein and
inhibit the proliferation of PDAC cells. The results provide a theoretical basis
for the study of miR-891b as an independent prognostic predictor of PDAC and the
role of miR-891b/Cbl-b pathway in this prediction, as well as the identification
of new targets for PDAC.
PMID- 27494900
TI - Employing an orthotopic model to study the role of epithelial-mesenchymal
transition in bladder cancer metastasis.
AB - Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression
of bladder cancer. To study its contribution to bladder cancer metastasis, we
established new xenograft models derived from human bladder cancer cell lines
utilizing an orthotopic "recycling" technique that allowed us to isolate and
examine the primary tumor and its corresponding circulating tumor cells (CTC's)
and metastatic lesions. Using whole genome mRNA expression profiling, we found
that a reversible epithelial-to-mesenchymal transition (EMT) characterized by
TGFbeta pathway activation and SNAIL expression was associated with the
accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL
completely blocked CTC production and regional/distant metastasis. Using this
unique bladder cancer xenograft model, we conclude that metastasis is dependent
on a reversible EMT mediated by SNAIL.
PMID- 27494901
TI - Advanced new strategies for metastatic cancer treatment by therapeutic stem cells
and oncolytic virotherapy.
AB - The field of therapeutic stem cell and oncolytic virotherapy for cancer treatment
has rapidly expanded over the past decade. Oncolytic viruses constitute a
promising new class of anticancer agent because of their ability to selectively
infect and destroy tumor cells. Engineering of viruses to express anticancer
genes and specific cancer targeting molecules has led to the use of these systems
as a novel platform of metastatic cancer therapy. In addition, stem cells have a
cancer specific migratory capacity, which is available for metastatic cancer
targeting. Prodrug activating enzyme or anticancer cytokine expressing stem cells
successfully inhibited the proliferation of cancer cells. Preclinical models have
clearly demonstrated anticancer activity of these two platforms against a number
of different cancer types and metastatic cancer. Several systems using
therapeutic stem cells or oncolytic virus have entered clinical trials, and
promising results have led to late stage clinical development. Consequently,
metastatic cancer therapies using stem cells and oncolytic viruses are extremely
promising. The following review will focus on the metastatic cancer targeting
mechanism of therapeutic stem cells and oncolytic viruses, and potential
challenges ahead for advancing the field.
PMID- 27494902
TI - MiR-146a-5p inhibits cell proliferation and cell cycle progression in NSCLC cell
lines by targeting CCND1 and CCND2.
AB - Previous studies have indicated that miR-146a-5p acts as an oncogene in several
types of cancer, yet a tumor suppressor gene in others. In non-small cell lung
cancer (NSCLC), one report showed that it was downregulated and played the role
of tumor suppressor. However, another study showed that miR-146a-5p was
overexpressed in the serum of NSCLC patients compared to healthy controls.
Therefore, it is obvious that further study of the function of miR-146a-5p in
NSCLC is necessary to fully understand its importance. Herein, we have verified
that miR- 146a- 5p acts as a tumor suppressor in NSCLC. Our data revealed that
the expression level of miR-146a-5p was significantly decreased in several human
NSCLC cell lines, and also less abundant in human NSCLC tissues, when compared
with controls. Moreover, we observed that miR-146a-5p could suppress cell
proliferation, both in vitro and in vivo. Our results also showed that miR-146a
5p directly targeted the 3'-UTR of CCND1 and CCND2 mRNAs as well as decreased
their expression at both mRNA and protein levels, causing cell cycle arrest at
the G0/G1 phase. Furthermore, siRNA-mediated downregulation of CCND1 or CCND2
yielded the same effects on proliferation and cell cycle arrest as miR-146a-5p
upregulation did in the NSCLC cell lines. We confirmed that the expression of miR
146a-5p had negative relationship with CCND1 or CCND2. Besides, we also found
that miR-146a-5p could inhibit tumor growth in xengroft mouse models, and CCND1
and CCND2 were downregulated in miR-146a-5p overexpressed xengroft tumor tissues.
In summary, our results demonstrated that miR-146a-5p could suppress the
proliferation and cell cycle progression in NSCLC cells by inhibiting the
expression of CCND1 and CCND2.
PMID- 27494904
TI - Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug
exposures affect either outcome or adverse events? A systematic review.
AB - OBJECTIVES: The objectives of this study were to identify the amikacin dosage
regimens and drug concentrations consistent with good outcomes and to determine
the drug exposures related to nephrotoxicity and ototoxicity. METHODS: A
literature review was conducted in Medline, EMBASE and the Cochrane Central
Register of Controlled Trials. Full journal articles reporting randomized
controlled trials, controlled clinical trials, interrupted time series trials,
and controlled before and after studies involving amikacin therapeutic drug
monitoring (TDM) and dose adjustment were considered for inclusion. RESULTS:
Seventeen studies for inclusion were identified, comprising 1677 participants.
Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day.
Studies were generally designed to compare different aminoglycosides rather than
to assess concentration-effect relationships. Only 11 papers presented data on
target concentrations, rate of clinical cure and toxicity. Target peak
concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or
<5 mg/L. It was not clear whether these targets were achieved. Measured peaks
averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing;
troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies
reported rates of nephrotoxicity; auditory and vestibular toxicities were
reported in 12 and 8 studies. CONCLUSIONS: This systematic review found little
published evidence to support an optimal dosage regimen or TDM targets for
amikacin therapy. The use of alternative approaches, such as consensus opinion
and a review of current practice, will be required to develop guidelines to
maximize therapeutic outcomes and minimize toxicity with amikacin.
PMID- 27494903
TI - Identification of novel macrolides with antibacterial, anti-inflammatory and type
I and III IFN-augmenting activity in airway epithelium.
AB - BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses.
Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired
antiviral immunity are thought to be important factors in disease severity and
duration. Macrolides including azithromycin are often used to treat the above
diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are
also readily used in treatment, but may lack specificity. Ideally, new treatment
alternatives should suppress unwanted inflammation, but spare beneficial
antiviral immunity. METHODS: In the present study, we screened 225 novel
macrolides and tested them for enhanced antiviral activity against rhinovirus, as
well as anti-inflammatory activity and activity against Gram-positive and Gram
negative bacteria. Primary bronchial epithelial cells were grown from 10
asthmatic individuals and the effects of macrolides on rhinovirus replication
were also examined. Another 30 structurally similar macrolides were also
examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin,
showed superior induction (up to 5-fold, EC50 = 5-11 MUM) of rhinovirus-induced
type I IFNbeta, type III IFNlambda1 and type III IFNlambda2/3 mRNA and the IFN
stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5
also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5
showed antibacterial activity against Gram-positive Streptococcus pneumoniae;
however, it did not have any antibacterial properties compared with azithromycin
when used against Gram-negative Escherichia coli (as a model organism) and also
the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus
influenzae. Further non-toxic Mac5 derivatives were identified with various anti
inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data
support the idea that macrolides have antiviral properties through a mechanism
that is yet to be ascertained. We also provide evidence that macrolides can be
developed with anti-inflammatory, antibacterial and antiviral activity and show
surprising versatility depending on the clinical need.
PMID- 27494906
TI - Impact of AAC(6')-Ib-cr in combination with chromosomal-mediated mechanisms on
clinical quinolone resistance in Escherichia coli.
AB - OBJECTIVES: aac(6')-Ib-cr is the most prevalent plasmid-mediated fluoroquinolone
(FQ) resistance mechanism in Enterobacteriaceae. We aimed to analyse the
interplay between this plasmid-mediated gene and chromosomal-mediated quinolone
resistance mechanisms on both FQ resistance and bacterial fitness in Escherichia
coli. METHODS: E. coli ATCC 25922 and derived isogenic strains carrying
chromosomal-mediated quinolone resistance modifications (Ser83Leu-Asp87Asn in
GyrA, Ser80Arg in ParC and/or a marR gene deletion) were electroporated with a
pBK-CMV vector encoding AAC(6')-Ib-cr. The MICs of FQs were determined by
microdilution and bactericidal activity was determined using time-kill curves. A
peritoneal sepsis murine model was used to evaluate the in vivo impact. Bacterial
fitness was analysed using growth curves and competition assays. RESULTS: The
presence of the aac(6')-Ib-cr gene increased the MICs of ciprofloxacin and
norfloxacin 4-8-fold for all E. coli genotypes, independently of the initial
resistance level. Combination of the aac(6')-Ib-cr gene with three or four
chromosomal mechanisms was necessary to reach MIC values above the susceptible
category. Killing curve assays showed a clear selective advantage for survival in
strains harbouring the aac(6')-Ib-cr gene (up to 7 log10 cfu/mL after 24 h).
AAC(6')-Ib-cr significantly reduced the ciprofloxacin efficacy in vivo. In terms
of bacterial fitness cost, maximal OD was significantly lower for all strains
harbouring the aac(6')-Ib-cr gene, independently of chromosomal mutations
associated. CONCLUSIONS: The aac(6')-Ib-cr gene, in spite of producing low-level
resistance by itself, plays a relevant role in acquisition of a clinical level of
ciprofloxacin and norfloxacin resistance, when combined with three or four
chromosomal mutations, both in vitro and in vivo.
PMID- 27494905
TI - Therapeutic drug monitoring of vancomycin: a guideline of the Division of
Therapeutic Drug Monitoring, Chinese Pharmacological Society.
AB - BACKGROUND: Guideline development should be based on the quality of evidence,
balance of benefits and harms, economic evaluation and patients' views and
preferences. Therefore, these factors were considered in the development of a new
guideline for therapeutic drug monitoring (TDM) of vancomycin. OBJECTIVES: To
develop an evidence-based guideline for vancomycin TDM and to promote
standardized vancomycin TDM in clinical practice in China. METHODS: We referred
to the WHO Handbook for Guideline Development and used the Grading of
Recommendations Assessment, Development and Evaluation (GRADE) system to rate the
quality of evidence and grade the strength of recommendations, according to
economic evaluation and patients' views and preferences. We used the GRADE Grid
method to formulate the recommendations. RESULTS: The guideline presents
recommendations about who should receive vancomycin TDM, how to monitor
vancomycin efficacy and renal safety, therapeutic trough concentrations, time to
start initial vancomycin TDM, loading dose and how to administer and adjust the
vancomycin dose. CONCLUSIONS: We developed an evidence-based guideline for
vancomycin TDM, which provides recommendations for clinicians and pharmacists to
conduct vancomycin TDM in China.
PMID- 27494907
TI - Cluster-dependent colistin hetero-resistance in Enterobacter cloacae complex.
AB - OBJECTIVES: Aims of this study were to: (i) evaluate whether the cluster
membership could have an impact on hetero-resistance phenotype to colistin in the
Enterobacter cloacae complex (ECC); and (ii) determine the genetic mechanism of
colistin hetero-resistance in ECC. METHODS: A collection of 124 clinical isolates
belonging to 13 clusters were used to analyse the hetero-resistance phenotype
(MICs were determined using the broth microdilution method, Etest and population
analysis profiling). Different mutants (DeltaphoP, DeltaphoQ, DeltaphoPQ,
DeltapmrA, DeltapmrB, DeltapmrAB, DeltaarnE, DeltaarnF and DeltaarnBCADTEF) were
constructed and tested for their colistin hetero-resistance phenotype. RESULTS:
Based on broth microdilution and Etest results, it was shown that the hetero
resistance to colistin depended on the cluster: strains from clusters I, II, IV,
VII, IX, X, XI and XII were usually hetero-resistant, whereas those from clusters
III, V, VI, VIII and XIII were categorized as susceptible. However, for some
cluster V and VIII strains, a small proportion (<10-7) of cells appeared
resistant when tested by population analysis profiling. From a mechanistic point
of view, analysis of mutants revealed that the mechanism of hetero-resistance was
mainly due to the expression of the arn operon and the phoP/phoQ two-component
regulatory system. CONCLUSIONS: Because the colistin hetero-resistance appeared
cluster-dependent in the ECC, it should be advocated to determine the cluster of
the strain associated with the infection in parallel with the MIC of colistin.
The resistance mechanism may not be similar to other Enterobacteriaceae since
only the two-component regulatory system PhoP/PhoQ (and not PmrA/PmrB) seemed to
play a role in resistance regulation.
PMID- 27494908
TI - Management of skin and soft-tissue infections at a community teaching hospital
using a severity-of-illness tool.
AB - OBJECTIVES: Skin and soft-tissue infections (SSTIs) encompass a diverse range of
infections of varying severity. The Clinical Resource Efficiency Support Team
(CREST) scoring system stratifies patients into four classes (I = least severe to
IV = most severe) based on the Standardized Early Warning Score (SEWS). The
objective of this study was to apply CREST to hospitalized patients with SSTIs in
order to quantify disease severity and evaluate appropriateness of antibiotic
management. METHODS: This was a retrospective, hypothesis-generating, single
centre evaluation of hospitalized patients with SSTIs admitted in 2011. Based on
CREST classification, the empirical antimicrobial choices were categorized as
appropriate, over-treatment or under-treatment. RESULTS: A total of 369 patients
were screened and 200 met the inclusion criteria. The majority of patients were
classified as either CREST class I (n = 68) or class II (n = 102). Over-treatment
was more common in the less severe classes (88% and 32% in class I and class II,
respectively; P < 0.05). Sixty-three percent of class I (n = 43) were over
treated due to both the use of intravenous antibiotics when oral therapy was
sufficient and use of unnecessarily broad-spectrum antibiotics. In contrast, 25%
(n = 26) of class II were over-treated due to use of unnecessarily broad-spectrum
antibiotics. Overall clinical failure rates remained low with only 1%, 4% and 17%
of patients unable to achieve initial response in class II, class III and class
IV. CONCLUSIONS: Retrospective application of CREST identified opportunities to
improve the management of SSTIs. CREST can be of great value in discriminating
less-severe SSTIs, which can be treated on an outpatient basis.
PMID- 27494909
TI - Levels of bone markers in a population of infants exposed in utero and during
breastfeeding to tenofovir within an Option B+ programme in Malawi.
AB - OBJECTIVES: No data are available on bone metabolism in infants exposed to
tenofovir during breastfeeding. We investigated bone metabolism markers in the
first year of life in infants from mothers who received tenofovir, lamivudine and
efavirenz during pregnancy and 12 months of breastfeeding in a national Option B+
programme in Malawi. METHODS: Serum samples collected at 6 and 12 months in
tenofovir-exposed infants and in a small sample of tenofovir-unexposed infants
from the same clinical centre were analysed in batches for levels of bone
specific alkaline phosphatase (BAP; marker of bone formation) and of C-terminal
telopeptide of type I collagen (CTX; marker of bone resorption). RESULTS:
Overall, 136 tenofovir-exposed infants were evaluated. No infant had at either
timepoint CTX values above the upper normal limit, while most of them had at 6
and 12 months levels of BAP above the upper normal limit for the age range.
Levels of bone markers showed no differences by gender and no association with
growth parameters. Tenofovir-unexposed and -exposed children had similar mean
levels of bone markers at 6 months (CTX: 0.62 versus 0.55 ng/mL, P = 0.122; BAP:
384 versus 362 U/L, P = 0.631). CONCLUSIONS: No significant association between
treatment with tenofovir and CTX or BAP levels was found. The high levels of BAP,
coupled to the normal levels observed for CTX, might reflect primarily skeletal
growth. Potential negative effects of prolonged exposure to tenofovir through
breastfeeding cannot however be excluded and longitudinal studies that evaluate
bone mineralization status in children enrolled in Option B+ programmes are
warranted.
PMID- 27494910
TI - Tissue pharmacokinetics of telavancin in healthy volunteers: a microdialysis
study.
AB - BACKGROUND: Telavancin is a novel lipoglycoprotein antibiotic with MRSA activity.
To date, tissue pharmacokinetics (PK) and plasma protein binding of the drug are
insufficiently described. OBJECTIVES: To investigate tissue PK and plasma protein
binding of telavancin in healthy volunteers. METHODS: Eight male healthy subjects
received a single dose of 10 mg/kg of body weight of telavancin as an intravenous
infusion over 1 h. At defined timepoints before and up to 24 h after treatment,
total telavancin concentrations were measured in plasma. Additionally, unbound
telavancin levels were determined in plasma, muscle and subcutis by means of
microdialysis. RESULTS: Key PK parameters of total telavancin in plasma were in
good agreement with previously described values. Mean +/- SD Cmax and calculated
AUC0-24 of free telavancin in plasma were 13.8 +/- 7.8 mg/L and 82.9 +/- 34.3
mg.h/L, respectively. Unbound drug levels in plasma ranged from 13.2% to 24.8% of
corresponding total telavancin. Mean +/- SD Cmax and AUC0-24 of unbound
telavancin were 4.3 +/- 1.5 mg/L and 61.5 +/- 27.1 mg.h/L for muscle and 3.4 +/-
1.8 and 50.0 +/- 29.8 mg.h/L for subcutis, respectively. Relevant
PK/pharmacodynamic indices were calculated for total and unbound drug.
CONCLUSIONS: This study provides important information on soft tissue PK and
plasma protein binding of telavancin in healthy volunteers. Unbound plasma
concentrations above levels assumed from previously available data and sustained
free drug exposure in soft tissues support the current mode of administration.
PMID- 27494911
TI - Oral decontamination with aminoglycosides is associated with lower risk of
mortality and infections in high-risk patients colonized with colistin-resistant,
KPC-producing Klebsiella pneumoniae.
AB - OBJECTIVES: Invasive infections caused by KPC-producing Klebsiella pneumoniae
(KPCKP) are associated with very high mortality. Because infection is usually
preceded by rectal colonization, we investigated if decolonization therapy (DT)
with aminoglycosides had a protective effect in selected patients. METHODS:
Patients with rectal colonization by colistin-resistant KPCKP who were at high
risk of developing infection (because of neutropenia, surgery, previous recurrent
KPCKP infections or multiple comorbidities) were followed for 180 days. Cox
regression analysis including a propensity score was used to investigate the
impact of the use of two intestinal decolonization regimens with oral
aminoglycosides (gentamicin and neomycin/streptomycin) on mortality, risk of
KPCKP infections and microbiological success. The study was registered with
ClinicalTrials.gov (NCT02604849). RESULTS: The study sample comprised 77
colonized patients, of which 44 (57.1%) received DT. At 180 days of follow-up,
decolonization was associated with a lower risk of mortality in multivariate
analyses (HR 0.18; 95% CI 0.06-0.55) and a lower risk of KPCKP infections (HR
0.14; 95% CI 0.02-0.83) and increased microbiological success (HR 4.06; 95% CI
1.06-15.6). Specifically, gentamicin oral therapy was associated with a lower
risk of crude mortality (HR 0.15; 95% CI 0.04-0.54), a lower risk of KPCKP
infections (HR 0.86; 95% CI 0.008-0.94) and increased microbiological response at
180 days of follow-up (HR 5.67; 95% CI 1.33-24.1). Neomycin/streptomycin therapy
was only associated with a lower risk of crude mortality (HR 0.22; 95% CI 0.06
0.9). CONCLUSIONS: Intestinal decolonization with aminoglycosides is associated
with a reduction in crude mortality and KPCKP infections at 180 days after
initiating treatment.
PMID- 27494912
TI - Dose optimization of voriconazole/anidulafungin combination against Aspergillus
fumigatus using an in vitro pharmacokinetic/pharmacodynamic model and response
surface analysis: clinical implications for azole-resistant aspergillosis.
AB - BACKGROUND: Combination therapy of voriconazole with an echinocandin is often
employed in order to increase the efficacy of voriconazole monotherapy. METHODS:
Four clinical Aspergillus fumigatus isolates with different in vitro
susceptibilities to voriconazole (MIC 0.125-2 mg/L) and anidulafungin (MEC 0.008
0.016 mg/L) were tested in an in vitro pharmacokinetic/pharmacodynamic model
simulating human serum concentrations of standard dosages of voriconazole and
anidulafungin. Fungal growth was assessed using galactomannan production and
quantitative PCR. Drug concentrations were determined with bioassays.
Pharmacodynamic interactions were assessed using Bliss independence analysis (BI)
and Loewe additivity-based canonical mixture response-surface non-linear
regression analysis (LA). Probability of target attainment (PTA) was estimated
with Monte Carlo analysis for different doses of anidulafungin (25, 50 and 100
mg) and azole resistance rates (5%-25%). RESULTS: Synergy [BI 51% (8%-80%), LA
0.63 (0.38-0.79)] was found at low anidulafungin (fCmax/MEC <10) and voriconazole
(fAUC/MIC <10) exposures, whereas antagonism [BI 12% (5%-18%, LA 1.12 (1.04-4.6)]
was found at higher drug exposures. The largest increase in PTA was found with 25
mg of anidulafungin and voriconazole MIC distributions with high (>10%)
resistance rates. PTAs for isolates with voriconazole MICs of 1, 2 and 4 mg/L was
78%, 12% and 0% with voriconazole monotherapy and 96%-100%, 68%-82% and 9%-20%
with combination therapy, respectively. Optimal activity was associated with a
voriconazole tCmin/MIC ratio of 1.5 for monotherapy and 0.75 for combination
therapy. CONCLUSIONS: The present study indicated that the combination of
voriconazole with low-dose anidulafungin may increase the efficacy and reduce the
cost and potential toxicity of antifungal therapy, particularly against azole
resistant A. fumigatus isolates and in patients with subtherapeutic serum levels.
This hypothesis warrants further in vivo verification.
PMID- 27494914
TI - Molecular characterization of blaESBL-producing Escherichia coli cultured from
pig farms in Ireland.
AB - OBJECTIVES: To characterize ESBL-encoding Escherichia coli cultured from pigs and
their plasmids carrying these genes following conjugation into recipient strains.
METHODS: Six ESBL-producing E. coli were recovered from faecal samples taken from
pigs along with a further isolate from the environment of a farrowing house on
three pig farms in Ireland. These isolates were characterized by phylogenetic
grouping, MLST and ESBL genotype analyses. Conjugation experiments were carried
out in broth mating assays. S1-nuclease PFGE was used to determine the plasmid
profiles. Whole-genome sequences of the seven E. coli were determined and
subsequently analysed. RESULTS: Phylogenetic groups and the corresponding MLST
STs identified among the seven tested E. coli isolates included A/ST10, A/ST34,
C/ST23 and C/ST1629. All seven isolates carried one or more high-molecular-weight
plasmids and demonstrated the ability to transfer their cefotaxime resistance
phenotype at high frequencies. Five transmissible plasmid replicon types were
detected, including IncK/B (n = 3), IncI1 (n = 2), IncFIA (n = 1), IncFIB (n = 1)
and IncN (n = 1). ESBL-encoding genes, including blaCTX-M-14, blaCTX-M-15 and
blaTEM-20, were identified. CONCLUSIONS: As the first report from pig sources in
Ireland, characterization of these ESBL-encoding isolates and their transmissible
plasmids extends our understanding on these resistance markers from porcine E.
coli.
PMID- 27494913
TI - Tracking inter-institutional spread of NDM and identification of a novel NDM
positive plasmid, pSg1-NDM, using next-generation sequencing approaches.
AB - OBJECTIVES: Owing to gene transposition and plasmid conjugation, New Delhi
metallo-beta-lactamase (NDM) is typically identified among varied
Enterobacteriaceae species and STs. We used WGS to characterize the chromosomal
and plasmid molecular epidemiology of NDM transmission involving four
institutions in Singapore. METHODS: Thirty-three Enterobacteriaceae isolates
(collection years 2010-14) were sequenced using short-read sequencing-by
synthesis and analysed. Long-read single molecule, real-time sequencing (SMRTS)
was used to characterize genetically a novel plasmid pSg1-NDM carried on
Klebsiella pneumoniae ST147. RESULTS: In 20 (61%) isolates, blaNDM was located on
the pNDM-ECS01 plasmid in the background of multiple bacterial STs, including
eight K. pneumoniae STs and five Escherichia coli STs. In six (18%) isolates, a
novel blaNDM-positive plasmid, pSg1-NDM, was found only in K. pneumoniae ST147.
The pSg1-NDM-K. pneumoniae ST147 clone (Sg1-NDM) was fully sequenced using SMRTS.
pSg1-NDM, a 90 103 bp IncR plasmid, carried genes responsible for resistance to
six classes of antimicrobials. A large portion of pSg1-NDM had no significant
homology to any known plasmids in GenBank. pSg1-NDM had no conjugative transfer
region. Combined chromosomal-plasmid phylogenetic analysis revealed five clusters
of clonal bacterial NDM-positive plasmid transmission, of which two were inter
institution clusters. The largest inter-institution cluster involved six K.
pneumoniae ST147-pSg1-NDM isolates. Fifteen patients were involved in
transmission clusters, of which four had ward contact, six had hospital contact
and five had an unknown transmission link. CONCLUSIONS: A combined sequencing-by
synthesis and SMRTS approach can determine effectively the transmission clusters
of blaNDM and genetically characterize novel plasmids. Plasmid molecular
epidemiology is important to understanding NDM spread as blaNDM-positive plasmids
can conjugate extensively across species and STs.
PMID- 27494915
TI - Identification of non-PBP2a resistance mechanisms in Staphylococcus aureus after
serial passage with ceftaroline: involvement of other PBPs.
AB - OBJECTIVES: Ceftaroline (the active metabolite of ceftaroline fosamil) is a
cephalosporin that possesses activity against MRSA due to its differentiating
high affinity for PBP2a. It is known that PBP2a sequence variations, including
some outside of the transpeptidase-binding pocket, impact ceftaroline
susceptibility and recent evidence suggests involvement of non-PBP2a mechanisms
in ceftaroline resistance. This study evaluated the potential of ceftaroline to
select for resistant Staphylococcus aureus clones during serial passage. METHODS:
Selection experiments were performed by up to 20 daily passages of three S.
aureus isolates (two MRSA and one MSSA) in broth with increasing selective
pressure. Mutants that emerged were tested for changes in ceftaroline
susceptibility and genetically characterized. RESULTS: The MSSA isolate developed
mutations in PBP2 and PBP3 that increased the ceftaroline MIC by 16-fold and
increased the MICs of other beta-lactams. A Glu447Lys substitution in the PBP2a
transpeptidase pocket in one MRSA isolate elevated the ceftaroline MIC to 8 mg/L.
Selective pressure in a ceftaroline-resistant MRSA isolate generated mutations in
LytD, as well as changes in the pbp4 promoter previously shown to result in PBP4
overexpression, the one PBP not inhibited by ceftaroline. Elevated ceftaroline
MIC was reversed when tested in combination with extremely low levels of
methicillin or meropenem that could inhibit the function of PBP4. CONCLUSIONS:
These studies demonstrate that resistance to ceftaroline can be manifested
through numerous mechanisms. Further, they support a hypothesis where PBP4 can
functionally provide the essential transpeptidase activity required for MRSA cell
wall biogenesis when PBP2a is inhibited.
PMID- 27494916
TI - HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV
transmission in a preclinical model of HIV infection.
AB - BACKGROUND: Approximately 1.5 million HIV-positive women become pregnant
annually. Without treatment, up to 45% will transmit HIV to their infants,
primarily through breastfeeding. These numbers highlight that HIV acquisition is
a major health concern for women and children globally. They also emphasize the
urgent need for novel approaches to prevent HIV acquisition that are safe,
effective and convenient to use by women and children in places where they are
most needed. METHODS: 4'-Ethynyl-2-fluoro-2'-deoxyadenosine, a potent NRTI with
low cytotoxicity, was administered orally to NOD/SCID/gammac-/- mice and to bone
marrow/liver/thymus (BLT) humanized mice, a preclinical model of HIV infection.
HIV inhibitory activity in serum, cervicovaginal secretions and saliva was
evaluated 4 h after administration. 4'-Ethynyl-2-fluoro-2'-deoxyadenosine's
ability to prevent vaginal and oral HIV transmission was evaluated using highly
relevant transmitted/founder viruses in BLT mice. RESULTS: Strong HIV inhibitory
activity in serum, cervicovaginal secretions and saliva obtained from animals
after a single oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (10 mg/kg)
demonstrated efficient drug penetration into relevant mucosal sites. A single
daily oral dose of 4'-ethynyl-2-fluoro-2'-deoxyadenosine resulted in efficient
prevention of vaginal and oral HIV transmission after multiple high-dose
exposures to transmitted/founder viruses in BLT humanized mice. CONCLUSIONS: Our
data demonstrated that 4'-ethynyl-2-fluoro-2'-deoxyadenosine efficiently prevents
both vaginal and oral HIV transmission. Together with 4'-ethynyl-2-fluoro-2'
deoxyadenosine's relatively low toxicity and high potency against drug-resistant
HIV strains, these data support further clinical development of 4'-ethynyl-2
fluoro-2'-deoxyadenosine as a potential pre-exposure prophylaxis agent to prevent
HIV transmission in women and their infants.
PMID- 27494918
TI - Antimicrobial stewardship in wound care: a Position Paper from the British
Society for Antimicrobial Chemotherapy and European Wound Management Association.
AB - BACKGROUND: With the growing global problem of antibiotic resistance it is
crucial that clinicians use antibiotics wisely, which largely means following the
principles of antimicrobial stewardship (AMS). Treatment of various types of
wounds is one of the more common reasons for prescribing antibiotics. OBJECTIVES:
This guidance document is aimed at providing clinicians an understanding of: the
basic principles of why AMS is important in caring for patients with infected
wounds; who should be involved in AMS; and how to conduct AMS for patients with
infected wounds. METHODS: We assembled a group of experts in infectious
diseases/clinical microbiology (from the British Society for Antimicrobial
Chemotherapy) and wound management (from the European Wound Management
Association) who, after thoroughly reviewing the available literature and holding
teleconferences, jointly produced this guidance document. RESULTS: All open
wounds will be colonized with bacteria, but antibiotic therapy is only required
for those that are clinically infected. Therapy is usually empirical to start,
but definitive therapy should be based on results of appropriately collected
specimens for culture. When prescribed, it should be as narrowly focused, and
administered for the shortest duration, as possible. AMS teams should be
interdisciplinary, especially including specialists in infection and pharmacy,
with input from administrative personnel, the treating clinicians and their
patients. CONCLUSIONS: Available evidence is limited, but suggests that applying
principles of AMS to the care of patients with wounds should help to reduce the
unnecessary use of systemic or topical antibiotic therapy and ensure the safest
and most clinically effective therapy for infected wounds.
PMID- 27494917
TI - The impact of a multidisciplinary antimicrobial stewardship team on the
timeliness of antimicrobial therapy in patients with positive blood cultures: a
randomized controlled trial.
AB - BACKGROUND: Antimicrobial stewardship teams play an important role in assisting
with the optimization of antimicrobial use in acute care settings. We aimed to
determine whether a rapid review by a multidisciplinary antimicrobial stewardship
team would improve the timeliness of optimal antimicrobial therapy for patients
with positive blood cultures. METHODS: This prospective randomized controlled
trial was undertaken in two Australian hospitals. Patients received either
standard care (a clinical microbiologist, registrar or laboratory scientist
communicating the positive blood culture by phone to the treating doctor) or
intervention (standard care plus rapid review by a multidisciplinary
antimicrobial stewardship team). Outcomes included time to appropriate and/or
active antimicrobial therapy and in-hospital mortality. The trial was registered
on the Australian New Zealand Clinical Trials Registry (ACTRN12614000258651).
RESULTS: A total of 160 patients were enrolled in this study: 81 in the standard
care arm and 79 in the intervention arm. Patients in the intervention arm were
commenced earlier on active (HR 8.02, 95% CI: 2.15-29.91) and appropriate
antimicrobials (HR 1.95, 95% CI: 1.13-3.38), with a higher proportion of patients
allocated to the intervention arm receiving active therapy at 48 h (96% versus
82%) and appropriate therapy at 72 h (70% versus 54%). The majority of patients
where the blood culture was a contaminant were not started on antimicrobial
therapy, and there were no significant differences in time to cessation of
antimicrobial therapy. CONCLUSIONS: Antimicrobial stewardship team review of
patients with pathogenic positive blood cultures improved the time to both active
and appropriate antimicrobial therapy.
PMID- 27494919
TI - Use of WGS data for investigation of a long-term NDM-1-producing Citrobacter
freundii outbreak and secondary in vivo spread of blaNDM-1 to Escherichia coli,
Klebsiella pneumoniae and Klebsiella oxytoca.
AB - OBJECTIVES: An outbreak of NDM-1-producing Citrobacter freundii and possible
secondary in vivo spread of blaNDM-1 to other Enterobacteriaceae were
investigated. METHODS: From October 2012 to March 2015, meropenem-resistant
Enterobacteriaceae were detected in 45 samples from seven patients at Aalborg
University Hospital, Aalborg, Denmark. In silico resistance genes, Inc plasmid
types and STs (MLST) were obtained from WGS data from 24 meropenem-resistant
isolates (13 C. freundii, 6 Klebsiella pneumoniae, 4 Escherichia coli and 1
Klebsiella oxytoca) and 1 meropenem-susceptible K. oxytoca. The sequences of the
meropenem-resistant C. freundii isolates were compared by phylogenetic analyses.
In vitro susceptibility to 21 antimicrobial agents was tested. Furthermore, in
vitro conjugation and plasmid characterization was performed. RESULTS: From the
seven patients, 13 highly clonal ST18 NDM-1-producing C. freundii were isolated.
The ST18 NDM-1-producing C. freundii isolates were only susceptible to
tetracycline, tigecycline, colistin and fosfomycin (except for the C. freundii
isolates from Patient 2 and Patient 7, which were additionally resistant to
tetracycline). The E. coli and K. pneumoniae from different patients belonged to
different STs, indicating in vivo transfer of blaNDM-1 in the individual
patients. This was further supported by in vitro conjugation and detection of a
154 kb IncA/C2 plasmid with blaNDM-1. Patient screenings failed to reveal any
additional cases. None of the patients had a history of recent travel abroad and
the source of the blaNDM-1 plasmid was unknown. CONCLUSIONS: To our knowledge,
this is the first report of an NDM-1-producing C. freundii outbreak and secondary
in vivo spread of an IncA/C2 plasmid with blaNDM-1 to other Enterobacteriaceae.
PMID- 27494920
TI - Novel chromosome-encoded erm(47) determinant responsible for constitutive MLSB
resistance in Helcococcus kunzii.
AB - OBJECTIVES: The aim of the study was to identify the determinant responsible for
erythromycin resistance in Helcococcus kunzii clinical isolate UCN99 and to
characterize the genetic support and environment of this novel gene. METHODS:
MICs were determined using the broth microdilution method according to EUCAST
guidelines. The entire genome sequence of H. kunzii UCN99 was determined using a
454/Roche GS Junior sequencer. The fragment encompassing the new resistance gene
and its own promoter was cloned into the pAT29 shuttle vector and the recombinant
plasmid pAT29Omegaerm(47) was expressed in both Staphylococcus aureus and
Streptococcus agalactiae. The transcription start site (TSS) was experimentally
determined by 5' RACE-PCR. RESULTS: UCN99 exhibited a constitutive
macrolide/lincosamide/streptogramin B (MLSB) resistance phenotype, suggesting the
presence of an Erm protein. WGS allowed the identification of a novel gene, named
erm(47), encoding a protein sharing 44%-48% amino acid identity with known Erm
methylases. In both S. aureus and S. agalactiae, the introduction of
pAT29Omegaerm(47) conferred a significant increase (>=16-fold) in MICs of all
macrolides and lincosamides tested, as well as a 4-fold increase in MICs of
quinupristin (streptogramin B), confirming the MLSB resistance. The TSS
identification revealed the presence of a short leader peptide, potentially
implicated in a translational attenuation mechanism. It was also demonstrated
that erm(47) was harboured by a 81 kb genomic island integrated into a
chromosomal gene. CONCLUSIONS: This is the first description of a novel MLSB
resistance determinant, named erm(47). The prevalence of this gene among Gram
positive cocci must be further investigated to determine its clinical
significance.
PMID- 27494921
TI - Real-time PCR detection of Neisseria gonorrhoeae susceptibility to penicillin.
AB - OBJECTIVES: The objective of this study was to develop a real-time PCR assay
targeting the gonococcal porB gene (PorB-PCR) for predicting susceptibility of
Neisseria gonorrhoeae to penicillin. This complements a previously described PCR
assay for detecting penicillinase-producing N. gonorrhoeae (PPNG) developed by
our laboratory (PPNG-PCR). METHODS: The PorB-PCR assay was designed using six
probes to characterize various combinations of amino acids at positions 101 and
102 of the PorB1b class protein, including the WT G101/A102 and mutant
G101K/A102D, G101K/A102N and G101K/A102G sequences, as well as the PorB1a
sequence. The ability of these sequences to predict penicillin susceptibility was
initially assessed using 2307 N. gonorrhoeae isolates from throughout Australia
for which phenotypic susceptibility data were available. The assay was then
applied to N. gonorrhoeae-positive clinical specimens (n = 70). Specificity was
assessed by testing commensal Neisseria strains (n = 75) and N. gonorrhoeae
negative clinical specimens (n = 171). RESULTS: Testing of the 2307 N.
gonorrhoeae isolates using PorB-PCR to detect G101/A102 and PorB1a sequences
identified a total of 78.4% (61.2% and 17.2%, respectively) of penicillin
susceptible isolates with specificities of 97.4% and 99.3% and positive
predictive values of 98.8% and 98.9%, where PPNG strains were simultaneously
identified and excluded. Similar performance data were obtained when the PorB-PCR
assay was applied to the N. gonorrhoeae-positive clinical specimens. No false
positive results were observed for the N. gonorrhoeae-negative samples and no
cross-reactions were observed with the non-gonococcal species. CONCLUSIONS: When
used in parallel with the previously described PPNG-PCR, the PorB-PCR approach
has the potential to facilitate individualized treatment of gonorrhoea using
penicillin.
PMID- 27494923
TI - Molecular basis of rifampicin resistance in multiresistant porcine livestock
associated MRSA.
PMID- 27494922
TI - Polymyxin B in combination with doripenem against heteroresistant Acinetobacter
baumannii: pharmacodynamics of new dosing strategies.
AB - OBJECTIVES: Polymyxin B is being increasingly utilized as a last resort against
resistant Gram-negative bacteria. We examined the pharmacodynamics of novel
dosing strategies for polymyxin B combinations to maximize efficacy and minimize
the emergence of resistance and drug exposure against Acinetobacter baumannii.
METHODS: The pharmacodynamics of polymyxin B together with doripenem were
evaluated in time-kill experiments over 48 h against 108 cfu/mL of two polymyxin
heteroresistant A. baumannii isolates (ATCC 19606 and N16870).
Pharmacokinetic/pharmacodynamic relationships were mathematically modelled using
S-ADAPT. A hollow-fibre infection model (HFIM) was also used to simulate
clinically relevant polymyxin B dosing strategies (traditional, augmented 'front
loaded' and 'burst' regimens), together with doripenem, against an initial
inoculum of 109 cfu/mL of ATCC 19606. RESULTS: In static time-kill studies,
polymyxin B concentrations >4 mg/L in combination with doripenem 25 mg/L resulted
in rapid bactericidal activity against both strains with undetectable bacterial
counts by 24 h. The mathematical model described the rapid, concentration
dependent killing as subpopulation and mechanistic synergy. In the HFIM, the
traditional polymyxin B combination regimen was synergistic, with a >7.5 log10
reduction by 48 h. The polymyxin B 'front-loaded' combination resulted in more
rapid and extensive initial killing (>8 log10) within 24 h, which was sustained
over 10 days. With only 25% of the cumulative drug exposure, the polymyxin B
'burst' combination demonstrated antibacterial activity similar to traditional
and 'front-loaded' combination strategies. The polymyxin B 'front-loaded' and
'burst' combination regimens suppressed the emergence of resistance. CONCLUSIONS:
Early aggressive dosing regimens for polymyxin combinations demonstrate promise
for treatment of heteroresistant A. baumannii infections.
PMID- 27494924
TI - Aminoglycoside-associated acute kidney injury in elderly patients with and
without shock.
AB - OBJECTIVES: Multiresistant Gram-negative pathogens pose major healthcare concerns
with a limited therapeutic armamentarium. Aminoglycosides (AG) are under-utilized
due to nephrotoxicity. We aimed to evaluate AG-associated acute kidney injury (AG
AKI) in elderly inpatients, with and without shock. METHODS: We examined the
incidence and predictors of AG-AKI by KDIGO criteria and extended renal
dysfunction (ERD) in patients aged >60 years. ERD represented a composite of
hospital mortality or absence of renal recovery over 6 months following AG-AKI.
RESULTS: Two hundred and seventy-eight patients (aged 74 +/- 8 years) were
studied; 43% and 19% received >7 and >10 days of AG therapy, respectively, and
70% gentamicin (versus amikacin). Thirteen per cent had shock and 17% developed
AG-AKI. Comparing all patients with shock versus no shock, AG-AKI developed in
33% versus 14%, respectively (P = 0.005); correspondingly among 47 patients with
AG-AKI, more with shock had stage 2/3 AKI (92% versus 43%) and dialysis (50%
versus 9%) (P < 0.01), but more had other strong AKI confounders than AG therapy
alone (83% versus 40%, P = 0.02). Multivariate analyses identified mechanical
ventilation, frusemide administration and AG therapy >10 days as predictors of AG
AKI (P < 0.05), whereas shock, pneumonia and frusemide administration predicted
more severe stage 2/3 AG-AKI (P < 0.05). Hospital mortality was 30% versus 7%
with AG-AKI versus none (P < 0.001). Twenty-three of 211 (11%) patients with
extended analysis had ERD, with 47% experiencing renal recovery following AG-AKI.
Mechanical ventilation and contrast administration during index hospitalization
predicted ERD (P < 0.05). CONCLUSIONS: AG-AKI is common in the elderly, with a
significant risk of ERD, but the cause and severity are greatly influenced by
critical illness and shock, more so than AG therapy alone.
PMID- 27494925
TI - Pharmacodynamics for antifungal drug development: an approach for acceleration,
risk minimization and demonstration of causality.
AB - The treatment of invasive fungal diseases constitutes a significant unmet medical
need. There are relatively few antifungal agents in clinical development and a
paucity of novel targets. Morbidity and mortality remain high and clinical
outcomes are compromised by submaximal efficacy, emergence of drug resistance and
drug-related toxicity. Thus, new antifungal agents are urgently required. A deep
understanding of exposure-response relationships underpins the development of
safe and effective clinical regimens of any therapeutic agent. Pharmacokinetics
(PK) and pharmacodynamics (PD) is increasingly recognized as a vital tool in the
development of new antimicrobial agents and maximizes the probability that the
right dose will be studied the first time. There is currently no information or
agreement as to what constitutes an adequate PK/PD package for the development of
a new antifungal agent. This review provides a summary of the achievements of
antifungal PK/PD for the treatment of invasive candidiasis, invasive
aspergillosis and cryptococcal meningoencephalitis, and outlines the necessary
components of a PK/PD package for a new antifungal agent. Such information is
critical for the accelerated and efficient development of new agents and enables
improved clinical outcomes to be secured.
PMID- 27494926
TI - 1,3-beta-d-Glucan contamination of common antimicrobials-authors' response.
PMID- 27494927
TI - Escherichia coli antimicrobial susceptibility profile and cumulative antibiogram
to guide empirical treatment of uncomplicated urinary tract infections in women
in the province of Quebec, 2010-15.
AB - OBJECTIVES: Empirical treatment of uncomplicated urinary tract infections (UTIs)
in women should be based on local susceptibility data. We aimed to generate
regional and provincial cumulative antibiograms combining data from different
laboratory information systems and determine the impact of basic patient
characteristics on susceptibility results. METHODS: All positive urine samples
for Escherichia coli obtained from women aged 18-65 years old in outpatient
settings between 1 April 2010 and 31 March 2015 from four hospitals in Quebec,
Canada, were included. The cumulative antibiogram for ciprofloxacin,
nitrofurantoin and trimethoprim/sulfamethoxazole was calculated. A clinically
significant difference in susceptibility profile was defined as factor(s) that
lowered the susceptibility proportion below 80%. RESULTS: A total of 36 293
positive urine cultures were analysed. In the last year of the study, the
proportion of susceptibility for ciprofloxacin, nitrofurantoin and
trimethoprim/sulfamethoxazole was 90.3%, 95.4% and 81.9%, respectively. The
susceptibility proportion was <80% for trimethoprim/sulfamethoxazole in the
Montreal region (73.4%; 95% CI 71.1%-75.9%), whereas it remained >80% for the
other regions. A significant decrease in susceptibility with time was identified
for ciprofloxacin (92.1%-90.3%, P < 0.001) and nitrofurantoin (97.1%-95.4%, P <
0.001). Increasing age, recent hospitalization and site of collection were
associated with an increase in resistance for certain antibiotics. CONCLUSIONS:
Overall, all first-line antimicrobials remain acceptable choices for empirical
treatment of uncomplicated UTIs in women in Quebec. The regional variability in
susceptibility data within a single province emphasizes the importance of local
susceptibility data to inform the development of empirical treatment guidelines
for UTIs.
PMID- 27494928
TI - Mosaic tetracycline resistance genes encoding ribosomal protection proteins.
AB - First reported in 2003, mosaic tetracycline resistance genes are a subgroup of
the genes encoding ribosomal protection proteins (RPPs). They are formed when two
or more RPP-encoding genes recombine resulting in a functional chimera. To date,
the majority of mosaic genes are derived from sections of three RPP genes,
tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this
first review of mosaic genes, we report on their structure, diversity and
prevalence, and suggest that these genes may be responsible for an under-reported
contribution to tetracycline resistance in bacteria.
PMID- 27494929
TI - Comparative effectiveness of echinocandins versus fluconazole therapy for the
treatment of adult candidaemia due to Candida parapsilosis: a retrospective
observational cohort study of the Mycoses Study Group (MSG-12).
AB - OBJECTIVES: A polymorphism in the gene encoding beta-1,3-glucan synthase, the
target of the echinocandin class of antifungals, results in increased in vitro
MICs of the echinocandins. This has resulted in controversy surrounding use of
the echinocandins for treatment of Candida parapsilosis candidaemia. We aimed to
compare 30 day mortality in adults with C. parapsilosis candidaemia treated with
echinocandins versus fluconazole. METHODS: This is a retrospective observational
cohort study. We used the Premier Perspective Database to identify adult patients
with C. parapsilosis candidaemia treated with only fluconazole or only an
echinocandin as definitive therapy. The primary outcome was 30 day mortality.
Propensity scores were derived to estimate the probability the patient would have
received either an echinocandin or fluconazole. Inverse probability of treatment
weighting (IPTW) was used in a weighted logistic regression to calculate odds of
30 day mortality. RESULTS: There were 307 unique patients with C. parapsilosis
candidaemia. One hundred and twenty-six (41%) received fluconazole and 181 (59%)
received an echinocandin. Age, gender, race, year of admission, need for ICU
resources in the week prior to candidaemia onset, and receipt of vasopressors on
the day of candidaemia onset were included in the propensity score model used to
calculate inverse probability of treatment weights. Weighted logistic regression
demonstrated no difference in 30 day mortality between patients receiving an
echinocandin as compared with fluconazole (OR 0.82, 95% CI 0.33-2.07).
CONCLUSIONS: Our result supports the 2016 IDSA invasive candidiasis guidelines,
which no longer clearly favour treatment with fluconazole over an echinocandin
for C. parapsilosis candidaemia.
PMID- 27494930
TI - Impact of 48 weeks of atazanavir/ritonavir plus lamivudine dual therapy on
cellular HIV-DNA levels in the AtLaS pilot study.
PMID- 27494931
TI - Multiplication of blaOXA-23 is common in clinical Acinetobacter baumannii, but
does not enhance carbapenem resistance.
AB - OBJECTIVES: To investigate the copy number of blaOXA-23 and its correlation with
carbapenem resistance in carbapenem-resistant Acinetobacter baumannii (CRAB).
METHODS: A total of 113 blaOXA-23-positive clinical CRAB isolates were collected
from two hospitals in Zhejiang province, China. Their genetic relatedness was
determined by MLST. The MIC of imipenem was determined using the agar diffusion
method and the copy number of blaOXA-23 was measured using quantitative real-time
PCR (qRT-PCR). The complete genomes of five clinical CRAB strains were sequenced
using PacBio technology to investigate the multiplication mechanism of blaOXA-23.
RESULTS: Most of the isolates (100/113) belonged to global clone II and the MIC
of imipenem ranged from 16 to 96 mg/L. The gene blaOXA-23 resided exclusively in
Tn2006 or Tn2009. Approximately 38% of the isolates carried two or more copies of
blaOXA-23. The copy number of blaOXA-23 was not correlated with the MIC of
imipenem. Within the five sequenced strains, multiple copies of blaOXA-23 were
either tandemly clustered or independently inserted at different genomic sites.
CONCLUSIONS: Multiplication of blaOXA-23 is common in CRAB, but does not enhance
carbapenem resistance. Multiplication can be present in the form of either tandem
amplifications or independent insertions at different sites.
PMID- 27494933
TI - Head elevation by 3 vs. 6 cm in ProSeal laryngeal mask airway insertion: a
randomized controlled trial.
AB - BACKGROUND: The sniffing position (neck flexion by head elevation and head
extension) is commonly used for insertion of a laryngeal mask airway. However,
the appropriate degrees of head elevation and head extension are unclear. In the
present study, the success rate of ProSealTM laryngeal mask airway (LMA ProSeal)
insertion using two degrees of head elevation was evaluated. METHODS: This
prospective randomized, controlled study included 80 adult patients aged 18 to 90
years. In the 3 cm (n = 40) and 6 cm (n = 40) groups, the LMA ProSeal was
inserted while the head was elevated 3 cm and 6 cm, respectively, using a pillow
of the corresponding height. The success rate, and incidence of blood staining on
cuff, sore throat and hoarseness were assessed. The alignments of laryngeal and
oral axes were also evaluated. RESULTS: The first attempt success rate was higher
in the 3 cm than the 6 cm group (87 % vs. 60 %, P = 0.014). In 86 % of patients
in the 6 cm group and 50 % of patients in the 3 cm group in whom the second
attempt failed, the third insertion attempt was successful by using a pillow
height of the opposite group. The alignments of the two axes were not different
between the two groups (P > 0.05). CONCLUSIONS: The first attempt success rate of
ProSeal laryngeal mask insertion was higher with 3 cm than 6 cm head elevation in
adult patients. TRIAL REGISTRATION: Identifiers: NCT02058030 (08/05/2015), Unique
Protocol ID: phdkim1.
PMID- 27494932
TI - Using a gamified monitoring app to change adolescents' snack intake: the
development of the REWARD app and evaluation design.
AB - BACKGROUND: As the snacking pattern of European adolescents is of great concern,
effective interventions are necessary. Till now health promotion efforts in
children and adolescents have had only limited success in changing adolescents'
eating patterns and anthropometrics. Therefore, the present study proposes an
innovative approach to influence dietary behaviors in youth based on new insights
on effective behavior change strategies and attractive intervention channels to
engage adolescents. This article describes the rationale, the development, and
evaluation design of the 'Snack Track School' app. The aim of the app is to
improve the snacking patterns of Flemish 14- to 16-year olds. METHODS: The
development of the app was informed by the systematic, stepwise, iterative, and
collaborative principles of the Intervention Mapping protocol. A four week
mHealth intervention was developed based on the dual-system model with behavioral
change strategies targeting both the reflective (i.e., active learning, advance
organizers, mere exposure, goal-setting, monitoring, and feedback) and automatic
processes (i.e., rewards and positive reinforcement). This intervention will be
evaluated via a controlled pre-post design in Flemish schools among 1400
adolescents. DISCUSSION: When this intervention including strategies focused on
both the reflective and automatic pathway proves to be effective, it will offer a
new scientifically-based vision, guidelines and practical tools for public health
and health promotion (i.e., incorporation of learning theories in intervention
programs). TRIAL REGISTRATION: NCT02622165 registrated November 15, 2015 on
clinicaltrials.gov.
PMID- 27494934
TI - Onchocerciasis transmission in Ghana: the human blood index of sibling species of
the Simulium damnosum complex.
AB - BACKGROUND: Vector-biting behaviour is important for vector-borne disease (VBD)
epidemiology. The proportion of blood meals taken on humans (the human blood
index, HBI), is a component of the biting rate per vector on humans in VBD
transmission models. Humans are the definitive host of Onchocerca volvulus, but
the simuliid vectors feed on a range of animals and HBI is a key indicator of the
potential for human onchocerciasis transmission. Ghana has a diversity of
Simulium damnosum complex members, which are likely to vary in their HBIs, an
important consideration for parameterization of onchocerciasis control and
elimination models. METHODS: Host-seeking and ovipositing S. damnosum (sensu
lato) (s.l.) were collected from seven villages in four Ghanaian regions. Taxa
were morphologically and molecularly identified. Blood meals from individually
stored blackfly abdomens were used for DNA profiling, to identify previous host
choice. Household, domestic animal, wild mammal and bird surveys were performed
to estimate the density and diversity of potential blood hosts of blackflies.
RESULTS: A total of 11,107 abdomens of simuliid females (which would have
obtained blood meal(s) previously) were tested, with blood meals successfully
amplified in 3,772 (34 %). A single-host species was identified in 2,857 (75.7 %)
of the blood meals, of which 2,162 (75.7 %) were human. Simulium soubrense Beffa
form, S. squamosum C and S. sanctipauli Pra form were the most anthropophagic
(HBI = 0.92, 0.86 and 0.70, respectively); S. squamosum E, S. yahense and S.
damnosum (sensu stricto) (s.s.)/S. sirbanum were the most zoophagic (HBI = 0.44,
0.53 and 0.63, respectively). The degree of anthropophagy decreased (but not
statistically significantly) with increasing ratio of non-human/human blood
hosts. Vector to human ratios ranged from 139 to 1,198 blackflies/person.
CONCLUSIONS: DNA profiling can successfully identify blood meals from host
seeking and ovipositing blackflies. Host choice varies according to sibling
species, season and capture site/method. There was no evidence that HBI is vector
and/or host density dependent. Transmission breakpoints will vary among locations
due to differing cytospecies compositions and vector abundances.
PMID- 27494935
TI - Chicken interferome: avian interferon-stimulated genes identified by microarray
and RNA-seq of primary chick embryo fibroblasts treated with a chicken type I
interferon (IFN-alpha).
AB - Viruses that infect birds pose major threats-to the global supply of chicken, the
major, universally-acceptable meat, and as zoonotic agents (e.g. avian influenza
viruses H5N1 and H7N9). Controlling these viruses in birds as well as
understanding their emergence into, and transmission amongst, humans will require
considerable ingenuity and understanding of how different species defend
themselves. The type I interferon-coordinated response constitutes the major
antiviral innate defence. Although interferon was discovered in chicken cells,
details of the response, particularly the identity of hundreds of stimulated
genes, are far better described in mammals. Viruses induce interferon-stimulated
genes but they also regulate the expression of many hundreds of cellular
metabolic and structural genes to facilitate their replication. This study
focusses on the potentially anti-viral genes by identifying those induced just by
interferon in primary chick embryo fibroblasts. Three transcriptomic technologies
were exploited: RNA-seq, a classical 3'-biased chicken microarray and a high
density, "sense target", whole transcriptome chicken microarray, with each
recognising 120-150 regulated genes (curated for duplication and incorrect
assignment of some microarray probesets). Overall, the results are considered
robust because 128 of the compiled, curated list of 193 regulated genes were
detected by two, or more, of the technologies.
PMID- 27494937
TI - John McKessar Duncan.
PMID- 27494936
TI - An LPL-specific monoclonal antibody, 88B8, that abolishes the binding of LPL to
GPIHBP1.
AB - LPL contains two principal domains: an amino-terminal catalytic domain (residues
1-297) and a carboxyl-terminal domain (residues 298-448) that is important for
binding lipids and binding glycosylphosphatidylinositol-anchored high density
lipoprotein binding protein 1 (GPIHBP1) (an endothelial cell protein that
shuttles LPL to the capillary lumen). The LPL sequences required for GPIHBP1
binding have not been examined in detail, but one study suggested that sequences
near LPL's carboxyl terminus (residues ~403-438) were crucial. Here, we tested
the ability of LPL-specific monoclonal antibodies (mAbs) to block the binding of
LPL to GPIHBP1. One antibody, 88B8, abolished LPL binding to GPIHBP1. Consistent
with those results, antibody 88B8 could not bind to GPIHBP1-bound LPL on cultured
cells. Antibody 88B8 bound poorly to LPL proteins with amino acid substitutions
that interfered with GPIHBP1 binding (e.g., C418Y, E421K). However, the sequences
near LPL's carboxyl terminus (residues ~403-438) were not sufficient for 88B8
binding; upstream sequences (residues 298-400) were also required. Additional
studies showed that these same sequences are required for LPL binding to GPIHBP1.
In conclusion, we identified an LPL mAb that binds to LPL's GPIHBP1-binding
domain. The binding of both antibody 88B8 and GPIHBP1 to LPL depends on large
segments of LPL's carboxyl-terminal domain.
PMID- 27494938
TI - Role of Screening Tests in the Detection and Management of Blood Pressure
Abnormalities Among Young Population.
AB - The prevalence of hypertension is increasing among young population worldwide. So
there is an interest in detecting prehypertension and hypertension in childhood.
We determined blood pressure (BP) recorded at a screening test in a young
population. We retrospectively evaluated the medical records including systolic
blood pressure (SBP), diastolic blood pressure (DBP), weight, height, and body
mass index (BMI) of 685 male and 130 female apparently healthy adolescents. We
evaluated the prevalence of BP categories: normotension, prehypertension, and
hypertension. The prevalence of normotension (n = 369), prehypertension (n =
333), and hypertension (n = 113) was 45.3%, 40.9% and 13.9%, respectively;
prehypertension and hypertension were significantly higher among males. The
prevalence of prehypertension and hypertension was significantly higher among
overweight males and females. The BMI significantly correlated with SBP, DBP, and
heart rate among both genders. The prevalence of prehypertension and hypertension
is high among Turkish adolescents. Screening tests focused on BP and BMI
measurement may help detect the young population at risk of hypertension and
cardiovascular disease in the future.
PMID- 27494939
TI - Oncocytic Papillary Renal Cell Carcinoma in the Background of Renal Adenomatosis.
AB - Renal adenomatosis is a rare disease characterized by numerous adenomas in
bilateral kidneys. A literature review shows that malignant tumors can arise in
this condition. The present case describes an oncocytic papillary renal cell
carcinoma (PRCC) arising in renal adenomatosis. A 70-year-old man presented with
incidentally identified, multiple right renal masses on computed tomography.
Right nephrectomy was performed, and the resected kidney revealed numerous
radiologically undetected small nodules additionally. Microscopically, the
nodules were papillary neoplasms of variable sizes and cytological features. The
largest nodule measured 1.6 cm and was composed of oncocytic cells, meeting the
diagnostic criteria of oncocytic PRCC. The smaller nodules of papillary adenomas
and tiny lesions showing a single papillary ingrowth were also seen. This case
exhibits a spectrum of renal papillary neoplasms in a resected kidney and can be
a valuable case in the understanding of tumorigenesis.
PMID- 27494940
TI - Learn from the mistakes of care.data.
PMID- 27494941
TI - In vitro model for DNA double-strand break repair analysis in breast cancer
reveals cell type-specific associations with age and prognosis.
AB - Dysfunction of homologous recombination is a common denominator of changes
associated with breast cancer-predisposing mutations. In our previous work, we
identified a functional signature in peripheral blood lymphocytes from women who
were predisposed that indicated a shift from homologous recombination to
alternative, error-prone DNA double-strand break (DSB) repair pathways. To
capture both hereditary and nonhereditary factors, we newly established a
protocol for isolation and ex vivo analysis of epithelial cells, epithelial
mesenchymal transition cells (EMTs), and fibroblasts from breast cancer specimens
(147 patients). By applying a fluorescence-based test system, we analyzed the
error-prone DSB repair pathway microhomology-mediated end joining in these tumor
derived cell types and peripheral blood lymphocytes. In parallel, we investigated
DNA lesion processing by quantitative immunofluorescence microscopy of histone
H2AX phosphorylated on Ser139 focus after radiomimetic treatment. Our study
reveals elevated histone H2AX phosphorylated on Ser139 damage removal in
epithelial cells, not EMTs, and poly(ADP-ribose)polymerase inhibitor
sensitivities, which suggested a DSB repair pathway shift with increasing patient
age. Of interest, we found elevated microhomology-mediated end joining in EMTs,
not epithelial cells, from patients who received a treatment recommendation of
adjuvant chemotherapy, that is, those with high-risk tumors. Our discoveries of
altered DSB repair activities in cells may serve as a method to further classify
breast cancer to predict responsiveness to adjuvant chemotherapy and/or
therapeutics that target DSB repair-dysfunctional tumors.-Deniz, M., Kaufmann,
J., Stahl, A., Gundelach, T., Janni, W., Hoffmann, I., Keimling, M., Hampp, S.,
Ihle, M., Wiesmuller, L. In vitro model for DNA double-strand break repair
analysis in breast cancer reveals cell type-specific associations with age and
prognosis.
PMID- 27494942
TI - U.S. Food System Working Conditions as an Issue of Food Safety.
AB - Food workers' health and hygiene are common pathways to foodborne disease
outbreaks. Improving food system jobs is important to food safety because working
conditions impact workers' health, hygiene, and safe food handling. Stakeholders
from key industries have advanced working conditions as an issue of public safety
in the United States. Yet, for the food industry, stakeholder engagement with
this topic is seemingly limited. To understand this lack of action, we
interviewed key informants from organizations recognized for their agenda-setting
role on food-worker issues. Findings suggest that participants recognize the work
standards/food safety connection, yet perceived barriers limit adoption of a food
safety frame, including more pressing priorities (e.g., occupational safety);
poor fit with organizational strategies and mission; and questionable utility,
including potential negative consequences. Using these findings, we consider how
public health advocates may connect food working conditions to food and public
safety and elevate it to the public policy agenda.
PMID- 27494943
TI - Transition of Care From Pediatric to Adult Surgery.
PMID- 27494944
TI - Ethics Rounds: In the Eye of a Social Media Storm.
AB - Social media, no stranger to health care environments, is increasingly used by
patients, families, clinicians, and institutions to interact and engage in new
ways. The ethical challenges related to the use of social media in the clinical
setting are familiar, yet come with a novel twist, including the possibility of
having a conflict "go viral". Health care clinicians and institutions must
understand and embrace these technologies, while at the same time promoting
policies and practices that ensure the ethically appropriate use of social media
and address strategies for preventing and responding to a social media crisis.
PMID- 27494946
TI - Population Pharmacokinetics of Cefuroxime in Critically Ill Patients Receiving
Continuous Venovenous Hemofiltration With Regional Citrate Anticoagulation and a
Phosphate-Containing Replacement Fluid.
AB - BACKGROUND: Cefuroxime is frequently prescribed as an antimicrobial therapy in
critically ill patients. The aim of this study was to develop a new intravenous
dosing strategy for cefuroxime in critically ill patients undergoing continuous
venovenous hemofiltration with regional citrate anticoagulation (RCA-CVVH) by
analyzing its extracorporeal removal and pharmacokinetic (PK) parameters.
METHODS: Nine critically ill patients treated with intravenous cefuroxime and RCA
CVVH and a phosphate-containing replacement fluid were investigated. Arterial and
effluent samples were obtained from all patients and pre- and postfilter venous
blood samples were obtained from a subgroup of 5 patients. Plasma cefuroxime
levels were determined by ultraperformance liquid chromatography-mass
spectrometry in plasma samples collected before and after intravenous infusion of
either 1500 mg cefuroxime every 12 hours or 3000 mg continuously over 24 hours.
Population PK analysis and dosing simulations were performed using nonlinear
mixed-effects modeling and Monte Carlo simulations. RESULTS: The volume of
distribution (VD) of cefuroxime in the central compartment, corrected for lean
body mass, was 0.11 +/- 0.056 L/kgLBMc, CVVH-mediated clearance was 49.5-50.6
mL/min, the mean elimination half-life (t1/2) was 90 minutes (77-103), and the
mean sieving coefficient was 0.89 +/- 0.01. A 2-compartment model with between
subject variability in clearance, VD, and t1/2 described these data adequately.
Simulation of a standard dosing regimen (750 mg/12 hours) predicted failure to
achieve the international target plasma cefuroxime concentration (32 mg/L).
CONCLUSIONS: Cefuroxime clearance by RCA-CVVH was twice the reported clearance
during standard CVVH. Our PK data predicted that a maintenance dose of 3000 mg
cefuroxime, infused over 24 hours, would provide an optimal steady-state plasma
concentration of 38.5 mg/L. The developed population PK model for cefuroxime has
the potential to inform new dosing schedules in patients receiving cefuroxime
during RCA-CVVH.
PMID- 27494945
TI - Metabolic profiling of alcohol consumption in 9778 young adults.
AB - BACKGROUND: High alcohol consumption is a major cause of morbidity, yet alcohol
is associated with both favourable and adverse effects on cardiometabolic risk
markers. We aimed to characterize the associations of usual alcohol consumption
with a comprehensive systemic metabolite profile in young adults. METHODS: Cross
sectional associations of alcohol intake with 86 metabolic measures were assessed
for 9778 individuals from three population-based cohorts from Finland (age 24-45
years, 52% women). Metabolic changes associated with change in alcohol intake
during 6-year follow-up were further examined for 1466 individuals. Alcohol
intake was assessed by questionnaires. Circulating lipids, fatty acids and
metabolites were quantified by high-throughput nuclear magnetic resonance
metabolomics and biochemical assays. RESULTS: Increased alcohol intake was
associated with cardiometabolic risk markers across multiple metabolic pathways,
including higher lipid concentrations in HDL subclasses and smaller LDL particle
size, increased proportions of monounsaturated fatty acids and decreased
proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate
(P < 0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U
shaped associations with alcohol consumption. Results were coherent for men and
women, consistent across the three cohorts and similar if adjusting for body mass
index, smoking and physical activity. The metabolic changes accompanying change
in alcohol intake during follow-up resembled the cross-sectional association
pattern (R2 = 0.83, slope = 0.72 +/- 0.04). CONCLUSIONS: Alcohol consumption is
associated with a complex metabolic signature, including aberrations in multiple
biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with
long-term changes in alcohol consumption. These results elucidate the double
edged effects of alcohol on cardiovascular risk.
PMID- 27494947
TI - Evaluation of the New Siemens Tacrolimus Assay on the Dimension EXL Integrated
Chemistry System Analyzer: Comparison With an Ultra-Performance Liquid
Chromatography-Tandem Mass Spectrometry Method.
AB - BACKGROUND: Many patients are maintained at the lower end of the tacrolimus (TAC)
reference range (3-7 ng/mL), requiring the use of analytical methods displaying a
very low limit of quantification for their follow-up. Therefore, the new
Dimension TAC, based on affinity chrome-mediated immunoassay technology, was
evaluated on the Dimension EXL Integrated Chemistry System (Siemens Healthcare
Diagnostics Inc). The aims of this study were (1) to evaluate the analytical
performances with special emphasis on sensibility at low levels of TAC, (2) to
compare the results with an ultra-performance liquid chromatography-tandem mass
spectrometry (UPLC/MS/MS) method. METHODS: Analytical performance (imprecision,
linearity, limit of detection, and limit of quantification) was evaluated.
Comparison to UPLC/MS/MS was performed on 106 whole blood samples from 88
transplant recipients using regression analysis and Bland-Altman plot analysis.
RESULTS: Repeatability and within-laboratory coefficients of variation were <6%
at mean TAC control levels of 3.7, 11.7, and 19.2 ng/mL. Linearity was confirmed
between 1.0 and 22 ng/mL. Passing-Bablok regression analysis of Siemens TAC assay
in comparison with UPLC/MS/MS values displayed a slope of 1.09 and an intercept
of -0.42. Using Bland-Altman analysis, the mean bias was 0.27 ng/mL with 1.96 SD
limits of -2.14 and 2.67 ng/mL. CONCLUSIONS: The new Dimension TAC immunoassay on
the EXL analyzer demonstrated reliable and reproducible performances allowing
routine monitoring in transplant patients, even at TAC concentrations at the
lower end of the therapeutic range.
PMID- 27494948
TI - Ecological risk assessment for DvSnf7 RNA: A plant-incorporated protectant with
targeted activity against western corn rootworm.
AB - MON 87411 maize, which expresses DvSnf7 RNA, was developed to provide an
additional mode of action to confer protection against corn rootworm (Diabrotica
spp.). A critical step in the registration of a genetically engineered crop with
an insecticidal trait is performing an ecological risk assessment to evaluate the
potential for adverse ecological effects. For MON 87411, an assessment plan was
developed that met specific protection goals by characterizing the routes and
levels of exposure, and testing representative functional taxa that would be
directly or indirectly exposed in the environment. The potential for toxicity of
DvSnf7 RNA was evaluated with a harmonized battery of non-target organisms (NTOs)
that included invertebrate predators, parasitoids, pollinators, soil biota as
well as aquatic and terrestrial vertebrate species. Laboratory tests evaluated
ecologically relevant endpoints such as survival, growth, development, and
reproduction and were of sufficient duration to assess the potential for adverse
effects. No adverse effects were observed with any species tested at, or above,
the maximum expected environmental concentration (MEEC). All margins of exposure
for NTOs were >10-fold the MEEC. Therefore, it is reasonable to conclude that
exposure to DvSnf7 RNA, both directly and indirectly, is safe for NTOs at the
expected field exposure levels.
PMID- 27494950
TI - The Oxygen-Rich Beryllium Oxides BeO4 and BeO6.
AB - Two novel isomers of BeO4 with the structures OBeOOO and OBe(O3 ) in the
electronic triplet state have been prepared as well as the known disuperoxide
complex Be(O2 )2 in solid noble-gas matrices. We also report the synthesis of the
oxygen-rich bis(ozonide) complex Be(O3 )2 in the triplet state which has a D2d
equilibrium geometry. The molecular structures were identified by infrared
absorption spectroscopy with isotopic substitutions as well as quantum chemical
calculations.
PMID- 27494949
TI - Slow infusion rate of doxorubicin induces higher pro-inflammatory cytokine
production.
AB - Different infusion rates of doxorubicin (DOX) have been used for treating human
malignancies. Organ toxicity after DOX infusion is a major issue in treatment
disruption. However, whether different DOX infusion rates induce different
toxicity is still unknown. In this study, we examined the toxicity effects of
different DOX infusion rates in the early phase of organ toxicity. Thirty-six
rats were randomly divided into 5-, 15-, and 30-min infusion rate groups. A
single dose of DOX (8.3 mg/kg, I.V.) was administered at different infusion
rates. Blood samples were collected from the femoral artery at 1, 3, 6, 9, 12,
18, 24, 36, and 48 h after DOX administration. The blood cell count and blood
biochemistry were analyzed. The liver, kidney, and heart were removed for
pathological examinations after the rats were sacrificed. Our findings show that
the 30-min group had higher injury markers in the liver (glutamic oxaloacetic
transaminase and glutamic pyruvic transaminase), kidneys (blood urea nitrogen and
creatinine), and heart (creatine phosphokinase-MB and lactate dehydrogenase), and
had higher tumor necrosis factor-alpha and interleukin 6 levels than did the
other groups. The 30-min group also had more severe damage according to the
pathological examinations. In conclusion, slower infusion of DOX induced a higher
inflammatory response and greater organ damage.
PMID- 27494951
TI - Assessment of retinal vascular calibres as a biomarker of disease activity in
birdshot chorioretinopathy.
AB - PURPOSE: Birdshot chorioretinopathy (BCR) is a potentially blinding ocular
disorder involving the retinal vasculature and choroid without any systemic
manifestations. The objective of the study was to describe vascular calibre
changes in BCR and analyse the possibility of this optical biomarker for staging
and monitoring disease activity in BCR. METHODS: This retrospective case-control
study at a tertiary referral eye centre in the UK included 33 eyes from 21
patients with BCR and equal number of eyes from control subjects. Diagnosis of
BCR was confirmed on fundus fluorescein and indocyanine green angiography.
Vascular calibres were measured using validated semiautomated software. RESULTS:
Patients with BCR had smaller retinal venular calibres central retinal venular
equivalent (CRVE) than controls (211.3 versus 227.9 MUm, p = 0.008). After
adjusting for variables, the difference between the two groups for CRVE at
baseline was statistically significant based on two different analysis methods.
Central retinal venular equivalent (CRVE) was lower at the 6-month follow-up
visit (206.2 versus 213.8 MUm, p-value = 0.03), and arteriole-to-venule ratio was
larger (0.74 versus 0.71, p = 0.04) in subjects with BCR. Arteriolar calibre
(CRAE) remained the same. CONCLUSION: This study provides novel insight into the
pattern of vascular involvement in BCR. There was significant difference in the
CRVE in patients with BCR. More studies are needed to correlate this data with
visual function and treatment outcome and to validate the findings.
PMID- 27494952
TI - Symptomatic discoid lateral meniscus: a clinical and arthroscopic study in a
Chinese population.
AB - BACKGROUND: Discoid lateral meniscus (DLM) is relatively common in East
Asia..Symptomatic discoid lateral meniscus (SDLM) is an important indication for
knee arthroscopic surgery. However, studies investigating SDLM are rare. The
purpose of this study was to evaluate the clinical characteristics and intra
articular variants of SDLM in a Chinese population. METHODS: We retrospectively
reviewed all patients with SDLM from January 2005 to December 2014 in our
hospital. Clinical variables included gender, age, duration, age of onset,
affected side, symptoms and trauma history as well as arthroscopic findings: DLM
types, tear patterns and concomitant medial meniscus tear, which were evaluated
and compared statistically. RESULTS: Of the 496 consecutive participants with
SDLM, females outnumbered males (69.6 % vs. 30.4 %). The age of onset ranged from
3 to 80 years (median, 31 years), and was significantly higher in females than in
males (p < 0.0001). Trauma history in males was significantly higher than in
females (45 % vs. 35.1 %, p = 0.0356). Males showed a higher incidence of popping
and snapping, while females manifested higher range-of-motion (ROM) limitations
(p = 0.0179, and p = 0.0392, respectively). No significant difference in intra
articular variants was observed between genders. The complete type was the most
frequent (344, 69.4 %), followed by the incomplete type (149, 30 %), and the
Wrisberg type (3, 0.6 %). Significant difference in tear patterns was found
between complete and incomplete types (p < 0.0001). Few patients showed medial
meniscus tear (11, 2.2 %), at a significantly higher age compared with patients
without tear (median, 57 years vs. 33 years, p < 0.0001). CONCLUSIONS: The
majority of Chinese patients with SDLM are young and middle-aged females. Female
patients had an older age of onset, higher incidence of ROM limitation and
limited trauma history. The complete type is the most common, with tear patterns
varying between complete and incomplete types. The SDLM does not significantly
affect the medial meniscus.
PMID- 27494954
TI - Cancer Risk Factor Knowledge Among Young Adults.
AB - Cancer is the second leading cause of death in the USA. Incidence and mortality
rates for cancer have risen steadily and cost the healthcare system over $264
billion annually. Cancer risk can be reduced by restricting alcohol consumption,
avoiding tobacco, eating a balanced diet, limiting sun exposure, exercising, and
seeking routine cancer screenings. The purpose of this study is to examine cancer
risk factor knowledge among college students. Researchers surveyed undergraduate
and graduate students (n = 758) at a mid-sized public university in the Southeast
about their knowledge regarding cancer risk factors including smoking, alcohol
consumption, diet, obesity, hypertension, and human papillomavirus (HPV).
Participants were mostly able to identify the association between cancers and
health risk behaviors that have received widespread media coverage, are somewhat
intuitive, or are salient to their life stage such as drinking, tanning, and
smoking. Nearly all participants correctly reported exposure to ultraviolet (UV)
rays, and smoking increased risk of developing skin and lung cancer,
respectively. Most students correctly identified an increased risk of liver
cancer associated with alcohol use but missed head/neck and breast cancer.
However, knowledge of less publicized relationships was insufficient. The
findings offer encouragement to public health professionals that campaigns have
increased awareness of cancer risk. However, there were many relationships that
revealed a lack of knowledge, and future campaigns can target lesser-known cancer
risk relationships to reduce the personal tragedy and societal burden of cancer.
PMID- 27494953
TI - Associations between systemic inflammation, mycobacterial loads in sputum and
radiological improvement after treatment initiation in pulmonary TB patients from
Brazil: a prospective cohort study.
AB - BACKGROUND: Mycobacterium tuberculosis infection is known to cause inflammation
and lung tissue damage in high-risk populations. Nevertheless, direct
associations between mycobacterial loads, systemic inflammation and pulmonary
lesions upon treatment initiation have not been fully characterized. In the
present exploratory study, we prospectively depict the immune profile, microbial
clearance and evolution of radiographic lesions in a pulmonary tuberculosis (PTB)
patient cohort before and 60 days after anti-tuberculous treatment (ATT)
initiation. METHODS: Circulating levels of cytokines (IL-2, IL-4, IL-6, IL-10,
IFN-gamma, TNF-alpha) and C-reactive protein (CRP), as well as values of
erythrocyte sedimentation rate (ESR) were measured in cryopreserved serum samples
obtained from 73 PTB patients at pre-ATT and day 60 of treatment. Changes of the
immune profile over time were compared with mycobacterial loads in sputum and
culture conversion at day 60 of ATT. Additional analyses tested associations
between improvement of chest radiographic lesions at day 60 and pre-treatment
status of inflammation and mycobacterial loads. RESULTS: Within the inflammatory
parameters evaluated, values of CRP, IL-2, IL-4, TNF-alpha and ESR significantly
decreased upon treatment initiation. On the converse, IL-10 levels substantially
increased at day 60 of ATT, whereas concentrations of IL-6 and IFN-gamma remained
unchanged. Multidimensional analyses revealed that ESR, IL-2, IL-4 and CRP were
the parameters with the highest power to discriminate individuals before and
after treatment initiation. We further demonstrated that higher bacterial loads
in sputum at pre-ATT were associated with increased systemic inflammation and
higher risk for positive M. tuberculosis sputum cultures at day 60 of treatment.
Furthermore, we found that pre-ATT mycobacterial loads in sputum and systemic
inflammation synergistically associated with the status of radiographic lesions
during treatment (Relative risk for chest X-ray improvement: 10.0, 95 %
confidence interval: 2.4-40.0, P = 0.002). CONCLUSIONS: M. tuberculosis loads in
sputum are directly associated to the status of systemic inflammation and
potentially impact the immune profile, culture conversion and evolution of lung
lesions upon ATT initiation.
PMID- 27494955
TI - Two-stage Bayesian model to evaluate the effect of air pollution on chronic
respiratory diseases using drug prescriptions.
AB - Exposure to high levels of air pollutant concentration is known to be associated
with respiratory problems which can translate into higher morbidity and mortality
rates. The link between air pollution and population health has mainly been
assessed considering air quality and hospitalisation or mortality data. However,
this approach limits the analysis to individuals characterised by severe
conditions. In this paper we evaluate the link between air pollution and
respiratory diseases using general practice drug prescriptions for chronic
respiratory diseases, which allow to draw conclusions based on the general
population. We propose a two-stage statistical approach: in the first stage we
specify a space-time model to estimate the monthly NO2 concentration integrating
several data sources characterised by different spatio-temporal resolution; in
the second stage we link the concentration to the beta2-agonists prescribed
monthly by general practices in England and we model the prescription rates
through a small area approach.
PMID- 27494956
TI - Characterizing the spatial distribution of multiple pollutants and populations at
risk in Atlanta, Georgia.
AB - BACKGROUND: Exposure metrics that identify spatial contrasts in multipollutant
air quality are needed to better understand multipollutant geographies and health
effects from air pollution. Our aim is to improve understanding of: (1) long-term
spatial distributions of multiple pollutants; and (2) demographic characteristics
of populations residing within areas of differing air quality. METHODS: We
obtained average concentrations for ten air pollutants (p=10) across a 12 km grid
(n=253) covering Atlanta, Georgia for 2002-2008. We apply a self-organizing map
(SOM) to our data to derive multipollutant patterns observed across our grid and
classify locations under their most similar pattern (i.e, multipollutant spatial
type (MST)). Finally, we geographically map classifications to delineate regions
of similar multipollutant characteristics and characterize associated
demographics. RESULTS: We found six MSTs well describe our data, with profiles
highlighting a range of combinations, from locations experiencing generally clean
air to locations experiencing conditions that were relatively dirty. Mapping MSTs
highlighted that downtown areas were dominated by primary pollution and that
suburban areas experienced relatively higher levels of secondary pollution.
Demographics show the largest proportion of the overall population resided in
downtown locations experiencing higher levels of primary pollution. Moreover,
higher proportions of nonwhites and children in poverty reside in these areas
when compared to suburban populations that resided in areas exhibiting relatively
lower pollution. CONCLUSION: Our approach reveals the nature and spatial
distribution of differential pollutant combinations across urban environments and
provides helpful insights for identifying spatial exposure and demographic
contrasts for future health studies.
PMID- 27494957
TI - Non-stationary spatio-temporal modeling of traffic-related pollutants in near
road environments.
AB - A problem often encountered in environmental epidemiological studies assessing
the health effects associated with ambient exposure to air pollution is the
spatial misalignment between monitors' locations and subjects' actual residential
locations. Several strategies have been adopted to circumvent this problem and
estimate pollutants concentrations at unsampled sites, including spatial
statistical or geostatistical models that rely on the assumption of stationarity
to model the spatial dependence in pollution levels. Although computationally
convenient, the assumption of stationarity is often untenable for pollutants
concentration, particularly in the near-road environment. Building upon the work
of Fuentes (2001) and Schmidt et al. (2011), in this paper we present a non
stationary spatio-temporal model for three traffic-related pollutants in a
localized near-road environment. Modeling each pollutant separately and
independently, we express each pollutant's concentration as a mixture of two
independent spatial processes, each equipped with a non-stationary covariance
function with covariates driving the non-stationarity and the mixture weights.
PMID- 27494958
TI - Acute effects of aircraft noise on cardiovascular admissions - an interrupted
time-series analysis of a six-day closure of London Heathrow Airport caused by
volcanic ash.
AB - Acute noise exposure may acutely increase blood pressure but the hypothesis that
acute exposure to aircraft noise may trigger cardiovascular events has not been
investigated. This study took advantage of a six-day closure of a major airport
in April 2010 caused by volcanic ash to examine if there was a decrease in
emergency cardiovascular hospital admissions during or immediately after the
closure period, using an interrupted daily time-series study design. The
population living within the 55dB(A) noise contour was substantial at 0.7
million. The average daily admission count was 13.9 (SD 4.4). After adjustment
for covariates, there was no evidence of a decreased risk of hospital admission
from cardiovascular disease during the closure period (relative risk 0.97 (95% CI
0.75-1.26)). Using lags of 1-7 days gave similar results. Further studies are
needed to investigate if transient aircraft noise exposure can trigger acute
cardiovascular events.
PMID- 27494959
TI - Mitigating the effects of preferentially selected monitoring sites for
environmental policy and health risk analysis.
AB - The potential effects of air pollution are a major concern both in terms of the
environment and in relation to human health. In order to support both
environmental and health policy there is a need for accurate estimates of the
exposures that populations might experience. The information for this typically
comes from environmental monitoring networks but often the locations of
monitoring sites are preferentially located in order to detect high levels of
pollution. Using the information from such networks has the potential to
seriously affect the estimates of pollution that are obtained and that might be
used in health risk analyses. In this context, we explore the topic of
preferential sampling within a long-standing network in the UK that monitored
black smoke due to concerns about its effect on public health, the extent of
which came to prominence during the famous London fog of 1952. Abatement measures
led to a decline in the levels of black smoke and a subsequent reduction in the
number of monitoring locations that were thought necessary to provide the
information required for policy support. There is evidence of selection bias
during this process with sites being kept in the most polluted areas. We assess
the potential for this to affect the estimates of risk associated air pollution
and show how using Bayesian spatio-temporal exposure models may be used to
attempt to mitigate the effects of preferential sampling in this case.
PMID- 27494960
TI - How robust are the estimated effects of air pollution on health? Accounting for
model uncertainty using Bayesian model averaging.
AB - The long-term impact of air pollution on human health can be estimated from small
area ecological studies in which the health outcome is regressed against air
pollution concentrations and other covariates, such as socio-economic
deprivation. Socio-economic deprivation is multi-factorial and difficult to
measure, and includes aspects of income, education, and housing as well as
others. However, these variables are potentially highly correlated, meaning one
can either create an overall deprivation index, or use the individual
characteristics, which can result in a variety of pollution-health effects. Other
aspects of model choice may affect the pollution-health estimate, such as the
estimation of pollution, and spatial autocorrelation model. Therefore, we propose
a Bayesian model averaging approach to combine the results from multiple
statistical models to produce a more robust representation of the overall
pollution-health effect. We investigate the relationship between nitrogen dioxide
concentrations and cardio-respiratory mortality in West Central Scotland between
2006 and 2012.
PMID- 27494961
TI - Modelling collinear and spatially correlated data.
AB - In this work we present a statistical approach to distinguish and interpret the
complex relationship between several predictors and a response variable at the
small area level, in the presence of (i) high correlation between the predictors
and (ii) spatial correlation for the response. Covariates which are highly
correlated create collinearity problems when used in a standard multiple
regression model. Many methods have been proposed in the literature to address
this issue. A very common approach is to create an index which aggregates all the
highly correlated variables of interest. For example, it is well known that there
is a relationship between social deprivation measured through the Multiple
Deprivation Index (IMD) and air pollution; this index is then used as a
confounder in assessing the effect of air pollution on health outcomes (e.g.
respiratory hospital admissions or mortality). However it would be more
informative to look specifically at each domain of the IMD and at its
relationship with air pollution to better understand its role as a confounder in
the epidemiological analyses. In this paper we illustrate how the complex
relationships between the domains of IMD and air pollution can be deconstructed
and analysed using profile regression, a Bayesian non-parametric model for
clustering responses and covariates simultaneously. Moreover, we include an
intrinsic spatial conditional autoregressive (ICAR) term to account for the
spatial correlation of the response variable.
PMID- 27494962
TI - Air pollution and stroke - an overview of the evidence base.
AB - Air pollution is being increasingly recognized as a significant risk factor for
stroke. There are numerous sources of air pollution including industry, road
transport and domestic use of biomass and solid fuels. Early reports of the
association between air pollution and stroke come from studies investigating
health effects of severe pollution episodes. Several daily time series and case
crossover studies have reported associations with stroke. There is also evidence
linking chronic air pollution exposure with stroke and with reduced survival
after stroke. A conceptual framework linking air pollution exposure and stroke is
proposed. It links acute and chronic exposure to air pollution with pathways to
acute and chronic effects on stroke risk. Current evidence regarding potential
mechanisms mainly relate to particulate air pollution. Whilst further evidence
would be useful, there is already sufficient evidence to support consideration of
reduction in air pollution as a preventative measure to reduce the stroke burden
globally.
PMID- 27494963
TI - Editorial for SSTE special issue on Environment and Health.
PMID- 27494964
TI - [Not Available].
PMID- 27494966
TI - [Not Available].
PMID- 27494967
TI - [Not Available].
PMID- 27494965
TI - [Not Available].
AB - REFLEXIONS ABOUT NEW STRATEGIES OF RADIOTHERAPY FOR EARLY BREAST CANCER:
Radiotherapy (RT) remains a major treatment element in early breast cancer, with
a major impact on local control and survival. For ductal carcinoma in situ
(DCIS), RT reduces local recurrence (LR) rates by 50 to 60 % after conservative
surgery (both in situ and invasive). This was confirmed by four randomized trials
and one meta-analysis. For infiltrating breast cancers (IBC), RT also reduces LR
rates by 65 to 75 % after conservative surgery. Boost allows an additional
reduction of LR. RT is efficient in all age categories, but hypofractionated
schemes are particularly adapted to elderly women. Partial breast irrradiation
techniques are very much heterogeneous and lack follow-up. They should be used in
LR low-risk patients only and in the frame of controlled studies. Locoregional RT
for high-risk patients (especially in pN+) remains essential to reduce the
locoregional recurrence rate and to increase survival, as confirmed in several
meta-analyses. Four studies showed a survival benefit (2-3 %), thanks to internal
mammary chain irradiation in LR high-risk patients. Moreover, axillary RT seems
to be a likely valuable alternative to axillary dissection in case of sentinel
node invasion. Finally, with the modern techniques and dosimetric optimization,
RT toxicity was reduced, or even cancelled, arousing hope for a better increased
benefit for the patients in the future.
PMID- 27494968
TI - [Not Available].
AB - TREATMENT OF NSCLC WITH NIVOLUMAB: Chemotherapy with docetaxel has remained a
cornerstone of second-line treatment for more than 15 years, but it is associated
with an unfavorable safety profile. Recently, the results of 2 randomized phase
III trials assessing nivolumab in lung cancer, Check-Mate-017 and Check- Mate
057, have deeply changed our current clinical practice and open the debate for
further improvements in the clinical care of lung cancer. This paper explores the
recent findings about nivolumab in the second-line setting and discusses future
directions for nivolumab and other immune Oncology drugs.
PMID- 27494970
TI - [Not Available].
AB - THE ROLE OF RUXOLITINIB IN THE TREATMENT OF MYELOPROLIFERATIVE NEOPLASMS: The
discovery of the JAK2V617F mutation in 2005, present in 95% of polycythemia vera
(PV) and in 55% of myelofibrosis (MF) patients, opened the way for a new era of
targeted therapies for myeloproliferative neoplasms. Ruxolitinib was the first-in
class Janus Kinase (JAK) inhibitor approved for the management of these diseases.
In PV patients, conventional treatment strategies including aspirin, phlebotomy,
cytoreductive agents such as hydroxyurea and interferon, clearly provide clinical
benefits. However, some patients develop resistance or intolerance to these
treatments. Ruxolitinib has been approved for PV patients who are resistant to or
intolerant of hydroxyurea, based on the results of the phase 3 RESPONSE study.
This study showed that ruxolitinib improves hematocrit control, reduces
splenomegaly, and ameliorate disease-related symptoms as compared with best
available therapy. In MF patients, the only curative treatment is allogeneic stem
cell transplantation, but it remains restricted to a limited group of patients
with poor prognosis and who are eligible for such procedure associated with non
negligible transplant-related mortality. Other treatments are palliative and
unlikely to prolong survival. Ruxolitinib has been approved in the United States
for MF patients with intermediate or high-risk disease, and in Europe for disease
related splenomegaly or symptoms in adults with MF, based on phase 3 COMFORT-I
and COMFORT-II studies. These studies showed that ruxolitinib was able to reduce
splenomegaly, ameliorate symptoms, and improve survival. However, the journey is
not finished yet since there are still important unmet needs for MF patients,
including improvement in cytopenias, and significant modification of disease
natural history.
PMID- 27494971
TI - [Not Available].
PMID- 27494969
TI - [Not Available].
AB - BIOLOGICAL ASPECTS OF JAK/STAT SIGNALING IN BCR-ABL-NEGATIVE MYELOPROLIFERATIVE
NEOPLASMS: Myeloproliferative disorders more recently named Myeloproliferative
neoplasms (MPN) display several clinical entities: chronic myeloid leukemia
(CML), the classical MPN including polycythemia vera (PV), essential
thrombocythemia (ET), primary myelofibrosis (PMF) and atypical and unclassifiable
NMP. The term MPN is mostly used for classical BCR-ABL-negative
(myeloproliferative disorder) (ET, PV, PMF). These are clonal diseases resulting
from the transformation of an hematopoietic stem cell and leading to an abnormal
production of myeloid cells. The genetic defects responsible for the
myeloproliferative abnormalities are called " driver " mutations and all result
in deregulation of the cytokine receptor / JAK2 / STAT axis. Among them, JAK2,
the thrombopoietin receptor (MPL) and calreticulin (CALR) mutations are found in
around 90% of the cases. These driver MPN mutations can be associated with other
driver mutations also found in other hematological malignancies, especially in
PMFs. These are chronic diseases with major risks being thrombosis, hemorrhage
and cytopenias for PMF and the long-term progression to myelofibrosis and the
transformation to leukemia. Most recent therapeutic have focused on targeting the
JAK2 signaling pathway directly by inhibitors of JAK2 or indirectly. Interferon a
allows in some cases hematologic and molecular remission patients.
PMID- 27494972
TI - [Not Available].
AB - FUNDAMENTAL BASIS OF METASTATIC PROCESS: Metastatic process is described as a
"dissemination of neoplastic cells in a distant secondary site, in which cells
proliferate to develop a mass of cells partially differentiated". The vast
majority of death in solid cancers is the consequence of metastasis development
which lead to vital organ dysfunction. In the present review, either recent
discoveries or controversial subjects associated with metastasis process will be
discussed. Indeed epithelia-mesenchymal transition (EMT), circulating tumor
cells, tumor dormancy, colonization in distant organ and cancer stem cells are
tackled.
PMID- 27494973
TI - [Not Available].
AB - ANTI-PD1 ROLE IN TREATMENT OF CUTANEOUS MELANOMA: The treatment of metastatic
melanoma dramatically changed over the last years. Two therapeutic revolutions
emerged in parallel, targeted anti-BRAF and anti-MEK therapies, for patients
BRAFV600 mutated and immunotherapy with immune checkpoint blockers using anti
CTLA-4 then anti-PD1 monoclonal antibodies. Indeed, melanoma immunotherapy was a
golden objective for many years but in spite of important efforts using cytokines
(interferon, interleukin) and different vaccine approaches no objective
improvement of patients 'prognosis was obtained. Ipilimumab, authorized in 2011,
was the first drug which showed a benefit of overall survival in patients with
metastatic melanoma in spite a low response rate (10-15) and the occurrence of
about 25% of serious toxicity. Anti-PD1 appear as a new generation of immune
checkpoint blockade with response rates between 30 to 40% of the patients, a
proven overall survival benefit as compared with chemotherapy or ipilimumab and
less toxicity than ipilimumab. Two molecules, pembrolizumab and nivolumab were
recently approved in monotherapy, for metastatic melanoma. Several questions
remain unresolved: the respective indications of anti-PD1 and targeted therapies
in first line therapy in patients with BRAF mutant melanoma, the benefit of
combining immunotherapy with radiotherapy or with targeted therapies, the optimal
treatment duration, and the benefit of the anti-PD1 in the adjuvant setting. The
combination of ipilimumab and nivolumab, recently approved by the FDA but not yet
in Europ, shows an improvement of the objective response rates (50-57%) and
progression free survival compared with nivolumab but is associated with an higer
incidence of serious adverse events (more than 50%).
PMID- 27494974
TI - [Not Available].
AB - OLIGOMETASTASIS AND OLIGOPROGRESSION: Oligometastic progression (or solitary
metastases) can justify ablative treatment for metastatic treatment. When such a
strategy is discussed, it is important to notice that definition of
oligometastases is not consensual both in terms of clinical presentation than on
the biological basis. Does a specific biological background truly exist and are
there markers that could predict for additional occult disease and its oligo or
polymetastatic profile in individuals with demonstrated oligometastasis. This
article provides a summary of the state of the art in this field and highlights
some current areas of controversies.
PMID- 27494975
TI - [Not Available].
AB - MOLECULAR EVALUATION OF METASTATIC DISEASE: WHY PATHOLOGY REMAINS (AND WILL
REMAIN) MANDATORY?: Numerous techniques are now available for the molecular
evaluation of a tissular or cellular sample in the context of metastatic disease.
They include in situ molecular techniques, such as immunohistochemistry for the
study of proteins and peptides, in situ hybridization for the study of nucleic
acids and in situ cytogenetics (FISH and its variants) for the demonstration of
chromosome alterations. They also include all the techniques of molecular
biology, which can now be applied to frozen as well as fixed tissue samples. The
combination of all these techniques makes it possible an integrated and coherent
approach, not limited to the description of DNA abnormalities, but able to
correlate genomic alterations with functional, and even structural changes. A
second major interest of the analysis of tissue samples is that they make it
possible to analyzing not only tumor cells, but also their environment, formed by
the stroma and its populations. The study of stroma and of stromal cells, in
particular of immune cells, is now of paramount importance for providing new
prognostic and predictive biomarkers, especially for anti-angiogenic strategies
and for cancer immunotherapy. Tissue analysis is therefore the only way to
perform a " total ", " phenogenomic " characterization of the tumor as an organ :
this is particularly important in the moment in which descriptive genomics is
substituted by functional genomics and integrated biology.
PMID- 27494976
TI - [Not Available].
AB - HOW A BIOMARKER CAN BECOME AN ACCEPTABLE SUBSTITUTION CRITERIA ?: Numerous
biomarkers of the treatment activity are now available as a result of the
fascinating progresses in biology and biotechnology. Together with the rapidly
growing understanding of the mechanisms of action of new agents, these biomarkers
provide promising tools to evaluate early the effect of treatments against
cancer. It is tempting to use these new markers of activity as primary endpoints
to evaluate new treatments in the context of randomized clinical trials.
Nevertheless, a mandatory preliminary step is to demonstrate that the two
endpoints carry the same information in order to validate whether the biomarker
is a surrogate of the final endpoint. We illustrate on several examples in
prostate, gastric and early breast cancer that it is important to distinguish two
levels of information: the individual level that allows to monitor a patient to
anticipate treatment failure, and the trial level that enables to predict the
treatment effect on the final endpoint based on the treatment effect measured on
the surrogate endpoint. In several cases, the formal validation turned out to be
disappointing despite strong biological rational.
PMID- 27494977
TI - [Not Available].
AB - THE BIG NATIONAL DATABASES AND STUDIES ON REAL WORLD DATA: EXAMPLE OF SARCOMAS IN
FRANCE: Sarcomas are rare and heterogeneous tumours, and improvement of knowledge
and of patient management need to gather and share data and biological material.
The French sarcoma database stores in a warehouse clinical, pathological,
molecular, therapeutic and follow-up data as well as data on samples and medical
practices. This database and the national structured networks constitute major
tools for the French Sarcoma Group.
PMID- 27494978
TI - [Not Available].
AB - NEOADJUVANT CHEMOTHERAPY IN HER2-POSITIVE AND TRIPLE-NEGATIVE BREAST CANCER:
Neoadjuvant chemotherapy is a standard option in the management of operable
breast cancer, as effective as adjuvant chemotherapy in term of survival and with
the potential to increase the rate of breast conservation. In HER2+ and triple
negative breast cancers, neoadjuvant chemotherapy is associated with a high
probability of pathological complete response, which strongly predicts survival
outcome. In HER2+ breast cancer, trastuzumab, in combination with neoadjuvant
chemotherapy, mostly anthracyclines and taxane-based, demonstrated a significant
increase in pathological complete response rate. Recently, dual HER2 blockade
strategies (lapatinib-trastuzumab or pertuzumab-trastuzumab) demonstrated a
significant improvement in terms of pathological complete response over
trastuzumab. In triple-negative breast cancer, recent data indicate that
incorporating platinum compounds to neoadjuvant chemotherapy also significantly
improves this parameter. Yet, in both subtypes, whether these substantial
improvements may lead to significant benefits in terms of survival and breast
conserving surgery remains to be demonstrated.
PMID- 27494979
TI - [Not Available].
PMID- 27494980
TI - [Not Available].
AB - SURGICAL DE-ESCALATION FOR INVASIVE BREAST CANCER TREATMENT: A surgical
therapeutic de-escalation is going to continue but necessarily has to design in a
progressive careful way and especially arranged with the other practitioners and
therapeutic methods. These strategies concern as well the surgery of the breast
as that of the axillary basin.
PMID- 27494981
TI - [Not Available].
AB - THERAPEUTIC DE-ESCALATION IN BREAST CANCER SURGERY: CONS: Therapeutic de
escalation in breast cancer surgery is not recommanded for all patients.
Concerning the axillary management, there are still some contraindications for
practicing sentinel node, and avoiding axillary dissection is not safe for more
than 3 positive sentinel nodes and in the absence of adjuvant treatment.
Mastectomy can also be preferred by patients rather than conservative surgery,
especially in case of genetic mutation, or for oncological reasons. Larger
glandular resections, known as oncoplasties, should also be chosen in case of
associated ductal carcinoma in situ and risky subgroups of local recurrence after
neoadjuvant therapy. Finally, all patients will not benefit from ambulatory
surgery.
PMID- 27494982
TI - [Not Available].
AB - DE-ESCALATION OF RADIOTHERAPY OF INFILTRATING BREAST CANCER: WHERE CAN WE GO?:
Adjuvant radiotherapy (RT) has an important role in the management of
infiltrating breast cancer, not only to improve local control but also overall
survival. So, all attempt of de-escalation must be performed in the context of
large prospective studies. However, RT could induce some complications and last 5
to 7 weeks. Three ways of RT de-escalation have been studied.
PMID- 27494983
TI - Comparison of different regimens of estradiol benzoate treatments followed by
long-acting progesterone to prepare noncycling mares as embryo recipients.
AB - The present study evaluated the influence of different regimens of estradiol
benzoate (EB) treatments followed by a single dose of long-acting progesterone
(LA P4) on plasma estrogen and P4 concentrations in noncyclic mares prepared as
embryo recipients. Twenty-one anestrous mares were distributed into three groups
(n = 7 mares per group), according to the EB dose received (single dose of 2.5
mg, total of 5 mg in decreasing doses, and total of 10 mg in decreasing doses),
which was followed by a single administration of 1500 mg of LA P4 in all groups.
Mares were reevaluated during the ovulatory phase and seven of them became part
of the cyclic nontreated control group. Ultrasonography was performed to monitor
endometrial edema, and blood samples were collected to measure estradiol (E2),
estrogen conjugate (EC), and P4 by RIA. Maximum uterine edema was achieved 24
hours after administration of EB in all treated groups. Maximum E2 concentrations
were observed 24 hours after the first EB injection in treated groups and there
were no differences (P > 0.05) among treatments. Maximum EC concentration was
observed 24 hours after the single EB injection in the 2.5-mg group, whereas in
the 5- and 10-mg groups EC peaks were observed 48 hours after the first EB
administration. Maximum P4 concentrations were detected 24 hours after LA P4
injection, although higher P4 concentrations were observed in the group treated
with 2.5 mg of EB than in that treated with 10 mg of EB (P < 0.05). Because P4
concentrations were reduced after administration of high doses of EB, we also
measured 17alpha-hydroxyprogesterone (17-OH-P) to test the hypothesis that high
concentrations of EB would accelerate the conversion of P4 to 17-OH-P. However,
17-OH-P concentrations paralleled P4 profile in all groups, irrespective of EB
doses. In summary, the three EB treatment regimens induced similar E2 peaks,
although the observation of EC peaks 24 hours after E2 peaks in the 5- and 10-mg
groups indicate that an excess of E2 was given, which was converted into EC to be
inactivated. Administration of 10 mg of EB reduced P4 concentrations 24 hours
after LA P4 was given. We demonstrated that the mechanism by which this reduction
occurred was not by an increase in P4 metabolism to 17alpha-OH-P. In conclusion,
the use of 2.5 mg of EB followed by 1500 mg of LA P4 appears to be a more
appropriate regimen to treat noncyclic mares, although additional studies are
needed to verify embryo survival with this treatment dose.
PMID- 27494984
TI - Frontal Lobe Epilepsy: A Primer for Psychiatrists and a Systematic Review of
Psychiatric Manifestations.
AB - BACKGROUND: Frontal lobe epilepsy (FLE) can masquerade as a primary psychiatric
condition, be misdiagnosed in-lieu of a true psychiatric disorder, or may be
comorbid with psychiatric illness. OBJECTIVES: To (1) qualitatively review
psychiatric manifestations of FLE and (2) to systematically review the cases/case
series of psychiatric manifestations of FLE presented in the literature to date.
METHODS: A systematic review of the literature was performed following the PRISMA
guidelines and using PubMed/Medline, PsychInfo, and Cochrane database of
systematic reviews to identify cases and case series of psychiatric
manifestations of FLE. RESULTS: A total of 35 separate articles were identified.
Further, 17 patients primarily presented with psychosis, 33 with affective
symptoms, and 16 with personality changes. Also, 62% of cases were males and 38%
were females. Ages ranged from 2-83 years with the average age of 32.7. Prior
psychiatric history was reported in 27.3% of cases. Causes of seizure were known
in 53%, with the most common causes being dysplasia and tumor. Only 6 cases
(<10%) did not have electroencephalographic correlations. Psychiatric
manifestations were primarily ictal in 74.3% of the cases. Associated
manifestations included motor (63.6%), cognitive (34.8%), and medical (9.0%)
findings. Surgery was required in 31.8% of the cases, whereas others were treated
with medications alone. All, but 3, patients were seizure free and saw an
improvement in symptoms with treatment. CONCLUSIONS: Given the complexity and
multifunctionality of the frontal lobes, FLE can present with complex,
psychiatric manifestations, with associated motor, cognitive, and medical
changes; thus, psychiatrists should keep FLE on the differential diagnosis of
complex neuropsychiatric cases.
PMID- 27494985
TI - The Psychosocial Assessment of Candidates for Transplantation: A Cohort Study of
its Association With Survival Among Lung Transplant Recipients.
AB - BACKGROUND: The United Network for Organ Sharing mandates a psychosocial
assessment of transplant candidates before listing. A quantified measure for
determining transplant candidacy is the Psychosocial Assessment of Candidates for
Transplant (PACT) scale. This instrument's predictive value for survival has not
been rigorously evaluated among lung transplantation recipients. METHODS: We
reviewed medical records of all patients who underwent lung transplantation at
Mayo Clinic, Rochester from 2000-2012. A transplant psychiatrist had assessed
lung transplant candidates for psychosocial risk with the PACT scale. Recipients
were divided into high- and low psychosocial risk cohorts using a PACT score
cutoff of 2. The main outcome variable was posttransplant survival. Mortality was
analyzed using the Kaplan-Meier estimator and Cox proportional hazard models.
RESULTS: This study included 110 lung recipients: 57 (51.8%) were females, 101
(91.8%) Whites, mean age: 56.4 years. Further, 7 (6.4%) recipients received an
initial PACT score <2 (poor or borderline candidates) and later achieved a higher
score, allowing transplant listing; 103 (93.6%) received initial scores >=2
(acceptable, good or great candidates). An initial PACT score < 2 was modestly
associated with higher mortality (adjusted hazard ratio = 2.73, p = 0.04).
CONCLUSIONS: Lung transplant recipients who initially received a low score on the
PACT scale, reflecting poor or borderline psychosocial candidacy, experienced
greater likelihood of mortality. This primary finding suggests that the
psychosocial assessment, as measured by the PACT scale, may provide additional
mortality risk stratification for lung transplant candidates.
PMID- 27494986
TI - When Is It Safe for Patients to Drive After Right Total Knee Arthroplasty?
AB - BACKGROUND: Advances in surgical technique and pain management have changed total
knee arthroplasty (TKA). How soon after TKA are patients able to return to
driving is a common question. Most surgeons prescribe 6-8 weeks postoperative
based on old literature. Our hypothesis is that patient who undergoes TKA with
contemporary techniques will return to their baseline before the 6th
postoperative week. METHODS: After institutional review board approval, 50
patients with right TKA were prospectively evaluated. All patients underwent a
preoperative brake reaction time (BRT), 2, 4, and 6 weeks postoperative. At each
testing, we ask them if they felt that they were ready to drive. RESULTS: Forty
seven patients completed the study protocol. Mean preoperative BRT was 0.692
seconds. At 2 weeks postoperative, the BRT was 0.631 seconds. Thirty-nine
patients (80%) reached their baseline by 2 weeks, and the remaining 10 (20%)
reached it at 4 weeks postoperative. Confounding variables revealed no
differences between groups. From the group that returned to baseline at 2 weeks,
67% patients stated they felt they were ready to drive, 21% patients said they
were not sure, and 12% patients stated they were not ready to drive. CONCLUSION:
BRT returned to baseline in most patients by the 2nd week postoperative and in
all patients by the 4th week. Patient perception of driving ability can predict
return of BRT. These findings have allowed us to encourage patients to reevaluate
their driving ability between the 2nd and 4th postoperative weeks after TKA.
PMID- 27494987
TI - Cutaneous manifestations in inflammatory bowel disease: a single institutional
study of non-neoplastic biopsies over 13 years.
AB - BACKGROUND: Skin is commonly affected by extraintestinal manifestations of
inflammatory bowel disease (IBD), but a controlled, systematic histopathologic
analysis of cutaneous lesions is lacking. METHODS: A total of 4147 classified IBD
[Crohn disease (CD) or ulcerative colitis (UC); 2000-2013] resections were cross
referenced with skin biopsies. Associated non-neoplastic skin biopsies were
categorized by basic reaction pattern and neutrophilic vs. granulomatous.
RESULTS: Of 4147 patients, 133 had non-neoplastic skin biopsies (106/2772, 3.7%
CD; 27/1375, 2% UC). Overall, miscellaneous > nodular and diffuse dermal >
spongiotic dermatitides were most common (31.6, 21.8 and 15%, respectively).
Spongiotic dermatitis, vasculitis, panniculitis and infections showed CD bias.
Psoriasiform, perivascular, nodular/diffuse dermal and bullous categories, as
well as neutrophilic processes, showed UC bias. Leukocytoclastic vasculitis,
panniculitis and pyoderma gangrenosum were exclusive to CD and psoriasis vulgaris
to UC. One CD patient had inverse psoriasis. CONCLUSIONS: Our findings show the
majority of dermatopathologic manifestations of IBD to have overlapping histology
or pathophysiology to intestinal disease; with a wider spectrum of histologic
patterns than typically discussed. Diseases 'classically' associated with IBD are
relatively rare biopsy specimens. Cutaneous manifestations of IBD are more common
in CD than UC and should be considered when reviewing an unexplained skin lesion
in an IBD patient.
PMID- 27494988
TI - Evaluation of joint type modelling in the human hand.
AB - This short communication presents preliminary results from an extensive
investigation of joint modelling for the human hand. We use finger and hand
movement data recorded from both hands of 110 subjects using passive reflective
markers on the skin. Furthermore, we use data which was recorded from a single
Thiel-fixated cadaver hand using also passive reflective markers but fixed to the
bone. Our data clearly demonstrate that, for wrist and finger joints, hinge joint
models are sufficiently accurate to describe their movement in Cartesian space.
PMID- 27494989
TI - A system to measure the pupil response to steady lights in freely behaving mice.
AB - BACKGROUND: Transgenic mice are widely used for the study of basic visual
function and retinal disease, including in psychophysical tests. Mice have a
robust pupillary light reflex that controls the amount of light that enters the
eye, and the attenuating effects of the pupil must be considered during such
tests. Measurement of the size of pupils at various luminance levels requires
that mice remain stable over prolonged periods of time; however, sedation of mice
with anesthesia and/or manual restraint can influence the size of their pupils.
NEW METHOD: We present a system to measure the pupillary light response to steady
lights of freely behaving mice using a custom-built, portable device that
automatically acquires close-up images of their eyes. The device takes advantage
of the intrinsic nature of mice to inspect objects of interest and can be used to
measure pupillary responses in optomotor or operant behavior testing chambers.
RESULTS: The size of the pupils in freely behaving mice decreased gradually with
luminance from a maximal area in the dark of 3.8mm2 down to a minimum 0.14mm2 at
80 scotopic cd/m2. The data was well fit with a Hill equation with Lo equal to
0.21cd/m2 and coefficient h=0.48. COMPARISON WITH EXISTING METHODS: These values
agree with prior measurements of the pupillary response of unrestrained mice that
use more laborious and time consuming approaches. CONCLUSIONS: Our new method
facilitates practical, straightforward and accurate measurements of pupillary
responses made under the same experimental conditions as those used during
psychophysical testing.
PMID- 27494990
TI - Relationships of CD163 and CD169 positive cell numbers in the endometrium and
fetal placenta with type 2 PRRSV RNA concentration in fetal thymus.
AB - Several routes of porcine reproductive and respiratory virus PRRSV transmission
across the porcine diffuse epitheliochorial placentation have been proposed, but
none have been proven. The objectives of this study were to investigate
associations between numbers of CD163 and CD169 positive macrophages, cathepsin
positive areolae, and type 2 PRRSV load at the maternal-fetal interface in order
to examine important factors related to transplacental infection. On gestation
day 85 +/- 1, naive pregnant gilts were inoculated with PRRSV (n = 114) or were
sham inoculated (n = 19). At 21 days post-inoculation (dpi), dams and their
litters were humanely euthanized and necropsied. Samples of the maternal-fetal
interface (uterus with fully attached placenta) and fetal thymus were collected
for analysis by RT-qPCR to quantify PRRSV RNA concentration. The corresponding
paraffin-embedded uterine tissue sections were subjected to immunohistochemistry
for PRRSV nucleocapsid N protein, CD163, CD169, and cathepsin. Our findings
confirm significant increases in the numbers of PRRSV, CD163 and CD169 positive
cells at the maternal-fetal interface during type 2 PRRSV infection in pregnant
gilts. PRRSV load in fetal thymus was positively related to CD163(+) cell count
in endometrium and negatively related to CD163(+) cell count in placenta, but
unrelated to CD169 counts or cathepsin positive areolae. The endometrium:placenta
ratio of CD163 cells, and to a lesser extent CD169 cells, was significantly
associated with an increase fetal viral load in thymus. These findings suggest a
more important role for CD163(+) cells following trans-placental PRRSV infection,
but dichotomous responses in endometrium and placenta for both CD163 and CD169
cells.
PMID- 27494991
TI - A framework to assess patient-reported adverse outcomes arising during
hospitalization.
AB - BACKGROUND: The assessment of adverse events from a patient-centered view
includes patient-reported adverse outcomes. An adverse outcome refers to any
suboptimal outcome experienced by the patient; when adverse outcomes are
identified through a patient interview these are called patient-reported adverse
outcomes. An adverse event is an adverse outcome that is more likely due to the
processes of medical care rather than to the mere progression of disease. In the
context of a large-scale study assessing post-hospitalization adverse events, we
developed a conceptual framework to assess patient-reported adverse outcomes
(PRAOs). This methodological manuscript describes this conceptual framework.
METHODS: The PRAO framework builds on a validated adverse event ascertainment
method including three phases: Phase 1 involves an inquiry to ascertain the
occurrence of any patient-reported adverse outcome. It is completed by a
structured telephone interview to obtain details - from a patient perspective -
on symptoms that developed and/or worsened after hospitalization. Phase 2
involves the classification of PRAOs by physicians not involved in the patient
care. Physician-reviewers then rate the PRAOs using well-adopted scales to
determine whether the occurrence was the natural progression of the underlying
illness or due to medical care. When the PRAO is rated as "due to medical care",
it is then classified as an "adverse event". Phase 3 involves the classification
of adverse events as preventable or ameliorable. RESULTS: Out of the 1347
patients contacted at 1-month post-discharge, 469 reported AOs and after
reviewing 369 cases, 29 were classified as AEs. Observed agreement levels between
raters were 87.3, 85.5, and 85.2 % respectively displaying a good agreement (k >
0.60). CONCLUSION: The framework incorporates PRAOs as a way to identify cases
that need to be evaluated for adverse events. Further validation of this
framework is warrant with the final aim of implementation at larger scale. The
implementation of this framework will enable clinicians, researchers and
healthcare institutions to compare outcome rates across providers and over time.
PMID- 27494992
TI - Timing of obstetrical assistance affects peripartal cardiac autonomic function
and early maternal behavior of dairy cows.
AB - Peripartal autonomic nervous system function and early maternal behavior were
investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated
into four groups based on the technology of calving management: 1) unassisted
calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen
(UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance
(ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP;
N=19). Heart rate, the high frequency (HF) component of heart rate variability
(HRV) as a measure of vagal activity and the ratio between the low frequency (LF)
and HF components (LF/HF ratio) as a parameter of sympathetic nervous system
activity were calculated. Heart rate and HRV parameters were presented as areas
under the curves (AUC) for the following periods: 1) prepartum period (between
96h before the onset of calving restlessness and the onset of restlessness), 2)
parturition (between the onset calving restlessness and delivery), and 3)
postpartum period (during a 48-h period after delivery). Pain-related behaviors
were recorded during parturition (i.e., the occurrence of vocalization and
stretching the neck towards the abdomen) and during a 2-h observation period
after calving (i.e., the occurrence of vocalization, stretching the neck towards
the abdomen and the duration of standing with an arched back). Early maternal
behavior was observed during the first 2h following calving as follows: 1)
latency and duration of sniffing calf's head/body, and 2) latency and duration of
licking calf's head/body. No difference was found across groups in autonomic
function before the onset of calving restlessness. Area under the heart rate
curve was higher in ACP cows during parturition (39.6+/-2.5beats/min*h) compared
to UCG, UCI and ACA animals (AUC=13.1+/-0.9beats/min*h, AUC=22.3+/-1.4beats/min*h
and AUC=25.0+/-2.1beats/min*h, respectively). Area under the heart rate curve did
not differ across the UCG, UCI and ACA groups during the postpartum period
(AUC=65.2+/-16.7beats/min*h, AUC=58.0+/-14.2beats/min*h and AUC=62.9+/
12.1beats/min*h, respectively) but it was higher in ACP cows compared to the
former groups (AUC=269.1+/-36.3beats/min*h). During parturition, area under the
HF curve reflected a lower vagal tone (AUC=-30.5+/-1.6n.u.*h) in cows with
premature obstetrical assistance than in animals that calved individually without
farmer assistance (AUC=2.7+/-0.4n.u.*h) or with appropriately timed assistance
(AUC=3.2+/-1.2n.u.*h). During parturition, LF/HF ratio showed greater sympathetic
activity in ACP cows than in animals from any other group. Area under the HF
curve was similar across UCG, UCI and ACA cows (AUC=-232.1+/-42.0n.u.*h, AUC=
163.4+/-35.6n.u.*h and AUC=-331.4+/-56.2n.u.*h, respectively) during the
postpartum period and was the lowest in ACP cows (AUC=-1025.6+/-44.2n.u.*h)
reflecting a long-term stress load in the latter group. During parturition, both
vocalization and stretching the neck towards the abdomen occurred more often in
UCG cows than in cows from any other groups, and the incidence of both behaviors
was statistically higher in ACP cows than in UCI and ACA animals. There were no
significant differences across groups in these behaviors during the 2-h
postpartum observation. UCG cows had a shorter latency and a longer duration of
maternal grooming during the first 2h following delivery compared to any other
groups. UCI and ACA dams spent more time with licking the calf within the 2-h
period after calving and had a shorter latency to sniff and lick the offspring
compared to cows that received premature assistance. Group calving is less
stressful for cows than calving in an individual pen either with or without
obstetrical assistance. Calving in a group or with appropriately timed farmer
assistance supports the expression of early maternal behavior and lead to a rapid
postpartum recovery of the autonomic nervous system. Premature obstetrical
assistance means stress for cows during parturition, leads to a prolonged
postpartum recovery of the autonomic nervous system and inhibits the expression
of early maternal behavior.
PMID- 27494993
TI - Computational strategies to explore antimalarial thiazine alkaloid lead compounds
based on an Australian marine sponge Plakortis Lita.
AB - In this work, an attempt was made to propose new leads based on the natural
scaffold Thiaplakortone-A active against malaria. The 2D QSAR studies suggested
that three descriptors correlate with the anti-malarial activity with an R2 value
of 0.814. Robustness, reliability, and predictive power of the model were tested
by internal validation, external validation, Y-scrambling, and applicability
domain analysis. HQSAR studies were carried out as an additional tool to find the
sub-structural fingerprints. The CoMFA and CoMSIA models gave Q2 values of 0.813
and 0.647, and [Formula: see text] values of 0.994 and 0.984, respectively. Using
the 2D-QSAR equation, the activity values of the seven modified compounds were
calculated and it was found that three molecules showed good anti-malarial
activity. Molecular docking of the 42 Thiaplakortone-A derivatives with
Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was carried
out to find out protein-ligand interactions. Data mining of the bioassay data-set
AID: 504850 using the classifier based on Random Forest of Weka suggested that
all of the eight molecules selected and three out of the seven virtual molecules
were anti-malarial active. Both the virtual molecules and drug molecules were
docked with CYP3A4, indicating that the virtual molecules could metabolize
easily. Toxicity studies using Osiris shows that three molecules showed no toxic
characters.
PMID- 27494994
TI - Excessive visceral fat area as a risk factor for early postoperative
complications of total gastrectomy for gastric cancer: a retrospective cohort
study.
AB - BACKGROUND: Obesity is a known risk factor for complications after digestive
surgery. Body mass index (BMI) is commonly used as an index of obesity but does
not always reflect the degree of obesity. Although some studies have shown that
high visceral fat area (VFA) is associated with poor outcomes in digestive
surgery, few have examined the relationship between VFA and total gastrectomy. In
this study, we demonstrated that VFA is more useful than BMI in predicting
complications after total gastrectomy. METHODS: Seventy-five patients who
underwent total gastrectomy for gastric cancer were enrolled in this study; they
were divided into two groups: a high-VFA group (n = 26, >=100 cm(2)) and a low
VFA group (n = 49, <100 cm(2)). We retrospectively evaluated the preoperative
characteristics and surgical outcomes of all patients and examined postoperative
complications within 30 days of surgery (including cardiac complications,
pneumonia, ileus, anastomotic leakage, pancreatic fistula, incisional surgical
site infection [SSI], abdominal abscess, and hemorrhage). RESULTS: The incidence
of anastomotic leakage (p = 0.03) and incisional SSI (p = 0.001) were higher in
the high-VFA group than in the low-VFA group. No significant differences were
observed in the other factors. We used univariate analysis to identify risk
factors for anastomotic leakage and incisional SSI. Age and VFA were risk factors
for anastomotic leakage, and BMI and VFA were risk factors for incisional SSI. A
multivariate analysis including these factors found that only VFA was a predictor
of anastomotic leakage (hazard ratio [HR] 4.62; 95 % confidence interval [CI]
1.02-21.02; p = 0.048) and incisional SSI (HR 4.32; 95 % CI 1.18-15.80; p =
0.027]. CONCLUSIONS: High VFA is more useful than BMI in predicting anastomotic
leakage and SSI after total gastrectomy. Therefore, we should consider the VFA
value during surgery.
PMID- 27494995
TI - Complete mitochondrial genomes of four entomopathogenic nematode species of the
genus Steinernema.
AB - BACKGROUND: Nematodes belonging to the genus Steinernema are insect parasites and
are used as effective biological agents against soil-dwelling insect pests.
Although the full nuclear genomes of multiple Steinernema species have become
available recently, mitochondrial genome information for the genus is limited. In
this study, we sequenced the complete mitochondrial genomes of four species of
Steinernema and analysed their structure, codon usage and phylogenetic
relationships. RESULTS: Mitochondrial genomes of Steinernema carpocapsae, S.
glaseri, S. kushidai and S. litorale comprised 13,924, 13,851, 15,182 and 21,403
bp, respectively, with highly AT-rich nucleotide contents (AT ratio of 71.05
76.76 %). All the expected genes, including 12 protein-coding genes (encoding
ATP6, CYTB, COX1-3, ND1-6 and ND4L), two rRNA genes and 22 tRNA genes were
identified in the four genomes. Phylogenetic analyses based on the amino acid
sequences of the 12 protein-coding genes identified the Steinernema species as
monophyletic, representing a sister clade of Rhabditina and Ascaridida. In
addition, they were more closely positioned to other Clade 10 nematodes,
including Bursaphelenchus xylophilus, Aphelenchoides besseyi and Panagrellus
redivivus, than to Strongyloides species. Gene arrangements and codon usage
analyses supported this relationship. Mitochondrial genome comparison of two
distinct strains of S. carpocapsae detected high intra-specific diversity.
CONCLUSIONS: The mitochondrial genomes of four species of Steinernema determined
in this study revealed inter- and intra-species divergences/diversities of
mitochondrial genomes in this genus. This information provides useful insights
into the phylogenetic position of the genus Steinernema within the Nematoda and
represents a useful resource for selecting molecular markers for diagnosis and
population studies. These data will increase our understanding of the interesting
biology of insect parasites.
PMID- 27494996
TI - Intraumbilical versus periumbilical incision in laparoscopic cholecystectomy: A
randomized controlled trial.
AB - INTRODUCTION: An important issue in laparoscopic surgery is initial peritoneal
access. An intraumbilical (IU) incision may be easier and faster to place, but
due to concerns about wound complications, the periumbilical (PU) incision is
still often used. A prospective randomized controlled study was performed to
investigate the outcomes of the IU incision and PU incision in laparoscopic
cholecystectomy. METHODS: Study subjects were patients who received laparoscopic
cholecystectomy for acute or chronic cholecystitis, gallbladder polyp or
adenomyomatosis, or porcelain gallbladder from June 2014 to January 2015.
Enrolled subjects were randomly allocated to the IU incision group or the PU
incision group. Demographic data, perioperative outcomes, and the results of a
cosmetic satisfaction questionnaire were analyzed. RESULTS: A total of 130
subjects were analyzed (64 in the IU group, 66 in the PU group). There were no
differences in patient demographics. The operation time was significantly shorter
in the IU group (34.2 +/- 14.6 vs 41.7 +/- 21.3, P = 0.020). The cosmetic survey
score was significantly higher in the IU group (36.8 +/- 5.2 vs 33.2 +/- 5.2, P <
0.001). There was no difference in the complication rates of the two groups.
CONCLUSIONS: The IU incision is a safe, feasible method of initial
intraperitoneal access that can reduce the operation time and offer superior
cosmetic effects to the patient.
PMID- 27494997
TI - Changing paradigms in the management of diverticulitis.
AB - The management of diverticular disease has evolved in the last few decades from a
structured therapeutic approach including operative management in almost all
cases to a variety of medical and surgical approaches leading to a more
individualized strategy. There is an ongoing debate among surgeons about the
surgical management of diverticular disease, questioning not only the surgical
procedure of choice, but also about who should be operated and the timing of
surgery, both in complicated and uncomplicated diverticular disease. This article
reviews the current treatment of diverticulitis, with a focus on the indications
and methods of surgery in both the emergency and elective settings. Further
investigation with good clinical data is needed for the establishment of clear
guidelines.
PMID- 27494998
TI - Laparoscopic insertion of the peritoneal catheter in ventriculoperitoneal
shunting. Review of 405 consecutive cases.
AB - BACKGROUND: Based upon our excellent previous experience with 151 adult patients
and 39 children whom had the peritoneal catheter in ventriculoperitoneal shunting
placed laparoscopically, we continued following this technique as a first-line
procedure in ventriculoperitoneal shunting. Now we analyzed our experience with
additional 405 cases for a better comprehension of the complications, advantages
and disadvantages of this procedure on this high number of patients. A strict
interdisciplinary setting with the maximum of medical intraoperative competence
was our goal and therefore better results. MATERIAL AND METHODS: N = 405 patients
with intraperitoneal shunt insertion from the years 2006-2013 (Follow-up period
ranges from 2 to 9 years with a 5,9-year mean follow-up period) were
retrospectively analyzed with a special focus on the possible peritoneal catheter
complications after laparoscopical shunt insertion. In our department all the
peritoneal catheters in ventriculoperitoneal shunting are inserted
laparoscopically, when there is no contraindication for this technique. RESULTS:
We had 0% peritoneal catheter misplacement rate with help of the laparoscopic
technique. In two cases (0.49%) injury of the small bowel could be repaired
immediately with no further action required. In two cases umbilical hernias have
been accidently discovered and the repair of the hernias took place in the same
surgical session. As this technique helps us to control the shunt position
intraperitoneally by direct laparoscopic vision, the patients spared an extra
radiation exposure, to control the position of the peritoneal catheter. A
diagnostic laparoscopy is also possible if needed. The time of the operation is
shortened in comparison with the needed time, which is mentioned in literature,
for the open laparotomy and of course the needed anesthesia and its possible
risks and complications decreased. CONCLUSION: No revision surgeries were
required because of any misplacement of the peritoneal catheter, no additional
technique related risks compared to the open surgical technique, no abdominal x
rays were needed, the operation time is shortened and the dose of anesthesia
needed is decreased and of course its possible side effects' rate is also
decreased. Another great benefit of this technique is the possibility of
accidental diagnosis of intra-abdominal pathologies. Also, if a surgical
treatment of this accidentally discovered intra-abdominal pathologies is needed,
it can take place in the same surgical session. No prolonged surgery time as the
laparoscopic technique is much easier, controllable and fast.
PMID- 27494999
TI - Prognostic value of presepsin for outcomes and complications in enterocutaneous
fistula complicated by abdominal sepsis.
AB - BACKGROUND: Enterocutaneous fistula (ECF) poses a supreme challenge for the
surgeons associated with abdominal sepsis, fluid electrolyte imbalance and
undernutrition. Individual prognostic stratification is pivotal in the clinical
management. Presepsin is a novel biomarker showing diagnostic and prognostic
value in sepsis. We aimed to evaluate the prognostic value of presepsin in ECF.
METHODS: Consecutive patients with ECF were enrolled if diagnosed as abdominal
sepsis from June 2014 to June 2015. Serum concentration of presepsin at admission
was measured, and medical records including demographics, medical history,
treatment modalities, complications and outcomes were collected. Kaplan-Meier
curves was drawn to demonstrate the cumulative incidence of source control of
infection and fistula closure, and Cox regression analysis was performed to
identify independent factors. Association between presepsin and other markers was
evaluated by Pearson's correlation coefficient. RESULTS: 71 patients were
included with the median presepsin concentration of 726 pg/mL at admission.
Baseline presepsin levels showed predictive potential in successful source
control of intra-abdominal infection but not in fistula closure. Patients with
higher presepsin had more severe intra-abdominal infection as denoted by higher
levels of WBC, CRP and PCT, as well as high risks of complications and failure of
fistula closure compared with those having lower presepsin (<=726 pg/mL).
Presepsin concentration was positively associated with APACHE II score, CRP and
PCT. CONCLUSIONS: Presepsin shows prognostic values for source control of
abdominal sepsis and clinical courses of ECF. This index may help stratify
patients, facilitating the monitoring and adjustment of the therapeutic regimen
at an early stage.
PMID- 27495000
TI - Nutritional quality of foods and non-alcoholic beverages advertised on Mexican
television according to three nutrient profile models.
AB - BACKGROUND: Evidence supports that television food advertisements influence
children's food preferences and their consumption. However, few studies have
examined the extent and nature of food marketing to children in low and middle
income countries. This study aims to assess the nutritional quality of foods and
beverages advertised on Mexican TV, applying the Mexican, World Health
Organization (WHO) European and United Kingdom (UKNPM) nutrient profile models,
before the Mexican regulation on food marketing came into effect. METHODS: We
recorded 600 h on the four national public and free TV channels with the highest
national ratings, from December 2012 to April 2013. Recordings were done for 40
randomly selected (week, weekend, school and vacation) days, from 7 am to 10 pm.
Nutritional information per 100 g/ml of product was obtained from the product
labels or company websites. RESULTS: A total of 2,544 food and non-alcoholic
beverage advertisements were broadcast, for 275 different products. On average,
the foods advertised during cartoon programming had the highest energy (367 kcal)
and sugar (30.0 g) content, while foods advertised during sport programming had
the highest amount of total fat (9.5 g) and sodium (412 mg) content. More than 60
% of the foods advertised did not meet any nutritional quality standards. 64.3 %
of the products did not comply with the Mexican nutritional standards, as
compared with 83.1 % and 78.7 % with WHO Europe and UKNPM standards,
respectively. The food groups most frequently advertised were beverages (24.6 %),
followed by chocolate and confectionery sugar (19.7 %), cakes, sweet biscuits and
pastries (12.0 %), savory snacks (9.3 %), breakfast cereals (7.1 %), ready-made
food (6.4 %) and dairy products (6.0 %). CONCLUSION: The majority of foods and
beverages advertised on Mexican TV do not comply with any nutritional quality
standards, and thus should not be marketed to children. The nutritional quality
standards applied by the Mexican regulation are much weaker than those applied by
the WHO Europe and United Kingdom. The Mexican government should improve the
nutrition standards in its new regulation, especially the sugar cut off points.
PMID- 27495001
TI - 15 Years of penile cancer management in the United States: An analysis of the use
of partial penectomy for localized disease and chemotherapy in the metastatic
setting.
AB - BACKGROUND: Penile cancer remains a rare disease in the United States, and its
understanding may be limited by the uncommon nature of the malignancy. We sought
to describe recent penile cancer treatment patterns using the National Cancer
Data Base. METHODS: A retrospective review of data obtained from the National
Cancer Data Base from 1998 to 2012 was performed. We obtained demographic
information and therapeutic approaches within the following2 clinical scenarios:
performance of partial penectomy for early stage disease (clinical Ta-T2) and the
use of chemotherapy for metastatic disease. Multivariate logistic analysis was
performed. RESULTS: A total of 2,677 patients presented with early stage penile
carcinoma. The proportion receiving partial penectomy increased from 74% in 1998
to 2000 to 80% in 2010 to 2012 (P<0.001). Partial penectomy was more common in
the elderly (age>80, odd ratios [OR] = 1.53, 95% CI: 1.05-2.23), young (age<50,
OR = 1.46, 95% CI: 1.02-2.07), and in African Americans (OR = 1.45, 95% CI: 1.00
2.12). Increasing tumor size was significantly associated with decreased
likelihood of receiving partial penectomy. Of those presenting with metastatic
disease (n = 819), use of chemotherapy increased over the time period from 39%
receiving chemotherapy in 1998 to 2000 to 49% in 2010 to 2012 (P<0.03). Patients
least likely to receive chemotherapy were older and with higher Comorbidity score
(both P<0.05), African American (OR = 0.46, 95% CI: 0.30-0.73), and living>=50
miles from the nearest treatment hospital (OR = 0.37, 95% CI: 0.25-0.55).
CONCLUSIONS: Penile-sparing surgery for early stage disease and the use of
chemotherapy for metastatic disease are becoming more commonly utilized over the
past several years. Further work is needed to define clinical and nonclinical
factors associated with the treatment.
PMID- 27495002
TI - Whole genome sequencing reveals mycobacterial microevolution among concurrent
isolates from sputum and blood in HIV infected TB patients.
AB - BACKGROUND: In the context of advanced immunosuppression, M. tuberculosis is
known to cause detectable mycobacteremia. However, little is known about the
intra-patient mycobacterial microevolution and the direction of seeding between
the sputum and blood compartments. METHODS: From a diagnostic study of HIV
infected TB patients, 51 pairs of concurrent blood and sputum M. tuberculosis
isolates from the same patient were available. In a previous analysis, we
identified a subset with genotypic concordance, based on spoligotyping and 24
locus MIRU-VNTR. These paired isolates with identical genotypes were analyzed by
whole genome sequencing and phylogenetic analysis. RESULTS: Of the 25 concordant
pairs (49 % of the 51 paired isolates), 15 (60 %) remained viable for extraction
of high quality DNA for whole genome sequencing. Two patient pairs were excluded
due to poor quality sequence reads. The median CD4 cell count was 32 (IQR; 16
101)/mm(3) and ten (77 %) patients were on ART. No drug resistance mutations were
identified in any of the sequences analyzed. Three (23.1 %) of 13 patients had
SNPs separating paired isolates from blood and sputum compartments, indicating
evidence of microevolution. Using a phylogenetic approach to identify the
ancestral compartment, in two (15 %) patients the blood isolate was ancestral to
the sputum isolate, in one (8 %) it was the opposite, and ten (77 %) of the pairs
were identical. CONCLUSIONS: Among HIV-infected patients with poor cellular
immunity, infection with multiple strains of M. tuberculosis was found in half of
the patients. In those patients with identical strains, whole genome sequencing
indicated that M. tuberculosis intra-patient microevolution does occur in a few
patients, yet did not reveal a consistent direction of spread between sputum and
blood. This suggests that these compartments are highly connected and potentially
seed each other repeatedly.
PMID- 27495004
TI - [Adjusted morbidity groups: A new multiple morbidity measurement of use in
Primary Care].
AB - The Adjusted Morbidity Groups (GMA) is a new morbidity measurement developed and
adapted to the Spanish healthcare System. It enables the population to be
classified into 6 morbidity groups, and in turn divided into 5 levels of
complexity, along with one healthy population group. Consequently, the population
is divided into 31 mutually exclusive categories. The results of the
stratification in Catalonia are presented. GMA is a method for grouping morbidity
that is comparable to others in the field, but has been developed with data from
the Spanish health system. It can be used to stratify the population and to
identify target populations. It has good explanatory and predictive results in
the use of health resources indicators. The Spanish Ministry of Health is
promoting the introduction of the GMA into the National Health System.
PMID- 27495003
TI - No difference in health-related quality of life, after a food challenge with
cashew nut in children participating in a clinical trial.
AB - BACKGROUND: Previous studies showed that health-related quality of life (HRQL)
significantly improved after the food challenge, with greater improvements in
HRQL after a negative outcome than after a positive outcome. It is currently
unknown whether this also occurs in patients undergoing DBPCFCs with cashew nut
in the context of a clinical trial. METHODS: Quality of life was studied in
children enrolled in a cashew nut study using Food Allergy Quality of Life
Questionnaires (FAQLQs). Children, teenagers and parents of the children
completed the questionnaires before the challenge test and 6 months after the
DBPCFC with cashew nut. The difference in the change in HRQL between the children
with a positive and negative DBPCFC outcome was studied by Mann-Whitney U-test.
RESULTS: In total, 112 children (67 boys, median age of 9 years) were included.
The children, teenagers and parents of the children completed 143 sets of
questionnaires in total. There were no significant differences in baseline total
and domain scores compared to the follow-up scores in the FAQLQ-CF, FAQLQ-TF and
FAQLQ-PF. In children, the delta FAIM score in the negative DBPCFC tested group
was significantly better than the delta FAIM score in the positive challenged
group (p = 0.026). There were no significant differences in the changes in the
scores of the FAQLQ-CF and FAQLQ-PF in the children with a positive challenge
outcome, compared to the children with a negative challenge result. However,
there was a significant difference in the change in score between the latter
groups in the domain 'accidental exposure' of the FAQLQ-TF (p = 0.049).
CONCLUSION: This study showed no difference in the change in HRQL scores after a
DBPCFC with cashew nut in children participating in a clinical trial. The utility
of HRQL as an outcome for clinical trials in food allergy may be limited if
participant baseline HRQL is relatively unimpaired.
PMID- 27495005
TI - Severe chronic osteomyelitis caused by Morganella morganii with high population
diversity.
AB - A case of chronic osteomyelitis probably caused by Morganella morganii, occurring
over a period of 30 years, is reported. The organism was identified through a
combination of sample culture, direct sequencing, and 16S RNA gene amplicon
sequencing. Further whole-genome sequencing and population structure analysis of
the isolates from the patient showed the bacterial population to be highly
diverse. This case provides a valuable example of a long-term infection caused by
an opportunistic pathogen, M. morganii, with high diversity, which might evolve
during replication within the host.
PMID- 27495006
TI - Infection of human uterine fibroblasts by Zika virus in vitro: implications for
viral transmission in women.
PMID- 27495007
TI - D-4F, an apolipoprotein A-I mimetic, inhibits TGF-beta1 induced epithelial
mesenchymal transition in human alveolar epithelial cell.
AB - Emerging evidences support that transforming growth factor beta1 (TGF-beta1)
induced epithelial-mesenchymal transition (EMT) participates in the pathogenesis
of pulmonary fibrosis and asthmatic airway remodeling. Recent studies
demonstrated that apolipoprotein A-I (Apo A-I) is the only known substance that
can resolve established pulmonary fibrotic nodules, and Apo A-I mimetic D-4F (a
synthetic polypeptide consisting of 18 amino acids) plays an inhibitory role in
murine asthmatic model. However, cellular mechanisms for such therapeutic effects
of Apo A-I and D-4F remain to be elucidated. This study evaluated the effects of
D-4F on TGF-beta1 induced EMT in human type II alveolar epithelial cell line
A549. A549 cells treated with 10ng/ml of TGF-beta1 manifested distinct EMT,
including fibroblastic morphological changes, down-regulation of epithelial
marker E-cadherin and up-regulation of mesenchymal marker vimentin. These EMT
related changes were all inhibited by D-4F in a concentration dependent manner.
Transcriptional investigation demonstrated clearly that D-4F dose-dependently
compensated for the reduced E-cadherin mRNA level and the increased vimentin mRNA
level in TGF-beta1 treated A549 cells. Translational analysis revealed that D-4F
significantly reversed the TGF-beta1 induced changes of E-cadherin and vimentin
levels. These results suggested that D-4F inhibits TGF-beta1 induced EMT in human
alveolar epithelial cell. Given the functional similarities between D-4F and Apo
A-I, it is speculated that D-4F and Apo A-I are able to exert possible anti
fibrotic and anti-asthmatic effects via inhibiting alveolar EMT, and D-4F may
possess beneficial clinical potential for patients suffering from pulmonary
fibrosis and asthma.
PMID- 27495008
TI - Is proteomics still knockin' on the hematological door?
PMID- 27495009
TI - Innovative biocatalytic production of soil substrate from green waste compost as
a sustainable peat substitute.
AB - In the present work, a new simple and quick eco-friendly method is discussed to
handle effectively the green wastes and produce a sustainable peat substitute of
high quality on the large scale. Principal physicochemical parameters, i.e.,
temperature, moisture, specific weight, pH, electrical conductivity and, also,
microorganisms, organic matter, humic substances, total Kjeldahl nitrogen and
total organic carbon, C/N ratio, ash, metal content and phytotoxicity, were
monitored systematically. Humic substances content values were interrelated to
both C/N ratio and pH values and, similarly, bulk density, TOC, TKN, C/N, GI, ash
and organic matter were found interconnected to each other. A novel biocatalyst,
extremely rich in soil microorganisms, prepared from compost extracts and peaty
lignite, accelerated the biotransformation. Zeolite was also employed. The
compost does not demonstrate any phytotoxicity throughout the entire
biotransformation process and has increased humic substances content. Both humic
substances content and germination index can be employed as maturation indices of
the compost. Addition of compost, processed for 60 days only, in cultivations of
grass plants led to a significant increase in the stem mass and root size,
annotating the significant contribution of the compost to both growth and
germination. The product obtained is comparable to peat humus, useful as peat
substitute and can be classified as a first class soil conditioner suitable for
organic farming.
PMID- 27495010
TI - Shoe soles as a potential vector for pathogen transmission: a systematic review.
AB - Shoe soles are possible vectors for infectious diseases. Although studies have
been performed to assess the prevalence of infectious pathogens on shoe soles and
decontamination techniques, no systematic review has ever occurred. The aim of
this study was to perform a systematic review of the literature to determine the
prevalence of infectious agents on shoe bottoms and possible decontamination
strategies. Three electronic bibliographic databases were searched using a
predefined search strategy evaluating prevalence of infectious pathogens on shoe
bottoms and decontamination strategies. Quality assessment was performed
independently by two reviews with disagreements resolved by consensus. Thirteen
studies were identified that supported the hypothesis that shoe soles are a
vector for infectious pathogens. Methicillin-resistant Staphylococcus aureus,
Clostridium difficile and multidrug-resistant Gram-negative species among other
pathogens were documented on shoe bottoms in the health care setting, in the
community and among food workers. Fifteen studies were identified that
investigated decontamination strategies for shoe soles. A number of
decontamination strategies have been studied of which none have been shown to be
consistently successful at disinfecting shoe soles. In conclusion, a high
prevalence of microbiological pathogens was identified from shoe soles studied in
the health care, community and animal worker setting. An effective
decontamination strategy for shoe soles was not identified. Studies are needed to
assess the potential for contaminated shoes to contribute to the transmission of
infectious pathogens.
PMID- 27495011
TI - NF-YC in glioma cell proliferation and tumor growth and its role as an
independent predictor of patient survival.
AB - Gliomas are tumors affecting the central nervous system and affecting
approximately 7/10,000 people with the median survival of only 14.6 months. As
such, there is a need to uncover and explore alternative targets and pathways of
gliomagenesis as well as a need to develop early and effective predictive markers
of the disease. In this study we utilized a wide range of patient glioma sections
to assess the characteristic expression of NF-YC and investigate whether NF-YC
could serve as an independent predictor of patient survival. Additionally, an in
vitro glioma model of manipulated NF-YC was used to investigate NF-YC's role in
the glioma growth process and ultimately validated in an animal model of tumor
growth. Here, we present evidence of the NF-YC subunit of the NF-Y transcription
factor complex as an independent prognostic maker for glioma patient survival. We
also describe that NF-YC is positively correlated with a universal marker of
cellular proliferation. Mechanistic investigation into the role of NF-YC in
gliomagenesis showed that NF-YC plays a role in cell cycle progression through
the inhibition of the cyclin-dependent kinase inhibitor p21. Finally, NF-YC plays
a role in the epithelial-mesenchymal transition preceding metastasis. We propose
a novel target of glioma cell proliferation, growth and metastasis. Additionally,
we identify NF-YC as a novel and independent predictor of patient survival to be
subsequently trialed.
PMID- 27495012
TI - GABA predicts visual intelligence.
AB - Early psychological researchers proposed a link between intelligence and low
level perceptual performance. It was recently suggested that this link is driven
by individual variations in the ability to suppress irrelevant information,
evidenced by the observation of strong correlations between perceptual surround
suppression and cognitive performance. However, the neural mechanisms underlying
such a link remain unclear. A candidate mechanism is neural inhibition by gamma
aminobutyric acid (GABA), but direct experimental support for GABA-mediated
inhibition underlying suppression is inconsistent. Here we report evidence
consistent with a global suppressive mechanism involving GABA underlying the link
between sensory performance and intelligence. We measured visual cortical GABA
concentration, visuo-spatial intelligence and visual surround suppression in a
group of healthy adults. Levels of GABA were strongly predictive of both
intelligence and surround suppression, with higher levels of intelligence
associated with higher levels of GABA and stronger surround suppression. These
results indicate that GABA-mediated neural inhibition may be a key factor
determining cognitive performance and suggests a physiological mechanism linking
surround suppression and intelligence.
PMID- 27495013
TI - Auditory white noise reduces age-related fluctuations in balance.
AB - Fall prevention technologies have the potential to improve the lives of older
adults. Because of the multisensory nature of human balance control, sensory
therapies, including some involving tactile and auditory noise, are being
explored that might reduce increased balance variability due to typical age
related sensory declines. Auditory white noise has previously been shown to
reduce postural sway variability in healthy young adults. In the present
experiment, we examined this treatment in young adults and typically aging older
adults. We measured postural sway of healthy young adults and adults over the age
of 65 years during silence and auditory white noise, with and without vision. Our
results show reduced postural sway variability in young and older adults with
auditory noise, even in the absence of vision. We show that vision and noise can
reduce sway variability for both feedback-based and exploratory balance
processes. In addition, we show changes with auditory noise in nonlinear patterns
of sway in older adults that reflect what is more typical of young adults, and
these changes did not interfere with the typical random walk behavior of sway.
Our results suggest that auditory noise might be valuable for therapeutic and
rehabilitative purposes in older adults with typical age-related balance
variability.
PMID- 27495014
TI - Memantine, an NMDA receptor antagonist, improves working memory deficits in
DGKbeta knockout mice.
AB - Diacylglycerol kinase (DGK) beta is a type 1 isozyme of the DGK family. We
previously reported that DGKbeta was deeply involved in neurite spine formation,
and DGKbeta knockout (KO) mice exhibited behavioral abnormalities concerning
spine formation, such as cognitive, emotional, and attentional impairment.
Moreover, some of these abnormalities were ameliorated by the administration of a
mood stabilizer. However, there is no data about how memory-improving drugs used
in the treatment of Alzheimer's disease affect DGKbeta KO mice. In the present
study, we evaluated the effect of an anti-Alzheimer's drug, memantine on the
working memory deficit observed in DGKbeta KO mice. In the Y-maze test, the
administration of memantine significantly improved working memory of DGKbeta KO
mice. We also found that the expression levels of the NR2A and NR2B N-methyl-d
aspartate (NMDA) receptor subunits were increased in the prefrontal cortex, but
decreased in the hippocampus of DGKbeta KO mice. These altered expression levels
of NR2 subunits might be related to the effect of an NMDA receptor antagonist,
memantine. Taken together, these findings may support the hypothesis that DGKbeta
has a pivotal role in cognitive function.
PMID- 27495015
TI - Effect of vitamin B supplementation on cancer incidence, death due to cancer, and
total mortality: A PRISMA-compliant cumulative meta-analysis of randomized
controlled trials.
AB - BACKGROUND: Observational studies have suggested that vitamin B supplementation
is associated with cancer risk, but this association remains controversial. A
pooled data-based meta-analysis was conducted to summarize the evidence from
randomized controlled trials (RCTs) investigating the effects of vitamin B
supplementation on cancer incidence, death due to cancer, and total mortality.
METHODS: PubMed, EmBase, and the Cochrane Library databases were searched to
identify trials to fit our analysis through August 2015. Relative risk (RR) was
used to measure the effect of vitamin B supplementation on the risk of cancer
incidence, death due to cancer, and total mortality using a random-effect model.
Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity
tests, and tests for publication bias were also conducted. RESULTS: Eighteen RCTs
reporting the data on 74,498 individuals were included in the meta-analysis.
Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer
related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B
supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95%
confidence interval [CI]: 0.98-1.10; P = 0.216), death due to cancer (RR, 1.05;
95% CI: 0.90-1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94-1.06;
P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence,
death due to cancer, and total mortality, the nonsignificance of the effect of
vitamin B persisted. With respect to specific types of cancer, vitamin B
supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95%
CI: 0.23-0.94; P = 0.032). CONCLUSION: Vitamin B supplementation does not have an
effect on cancer incidence, death due to cancer, or total mortality. It is
associated with a lower risk of skin melanoma, but has no effect on other
cancers.
PMID- 27495016
TI - Anatomic Study of Anterior Transdiscal Axial Screw Fixation for Subaxial Cervical
Spine Injuries.
AB - Anterior transdiscal axial screw (ATAS) fixation is an alternative or supplement
to the plate and screw constructs for the upper cervical spine injury. However,
no existing literatures clarified the anatomic feasibility of this technique for
subaxial cervical spine. Therefore, the objective of this study was to evaluate
the anatomical feasibility and to establish guidelines for the use of the ATAS
fixation for the subaxial cervical spine injury.Fifty normal cervical spines had
radiographs to determine the proposed screw trajectory (the screw length and
insertion angle) and the interbody graft-related parameters (the disc height and
depth, and the distance between anterior vertebral margin and the screw) for all
levels of the subaxial cervical spine. Following screw insertion in 8 preserved
human cadaver specimens, surgical simulation and dissection verified the
feasibility and safety of the ATAS fixation.Radiographic measurements showed the
mean axial screw length and cephalic incline angle of all levels were 41.2 mm and
25.2 degrees , respectively. The suitable depth of the interbody graft was >11.7
mm (the distance between anterior vertebral margin and the screw), but <17.1 mm
(disc depth). Except the axial screw length, increase in all the measurements was
seen with level up to C5-C6 segment. Simulated procedure in the preserved
specimens demonstrated that ATAS fixation could be successfully performed at C2
C3, C3-C4, C4-C5, and C5-C6 levels, but impossible at C6-C7 due to the obstacle
of the sternum. All screws were placed accurately. None of the screws penetrated
into the spinal canal and caused fractures determined by dissecting the
specimens.The anterior transdiscal axial screw fixation, as an alternative or
supplementary instrumentation for subaxial cervical spine injuries, is feasible
and safe with meticulous surgical planning.
PMID- 27495017
TI - Diagnose of occult bronchial foreign body: A rare case report of undetected
Chinese medicine aspiration for 10 long years.
AB - BACKGROUND: Occult bronchial foreign body can be very difficult to diagnose early
in an adult patient without acute symptoms. This report describes a rare case of
undetected Chinese medicine "Coptis chinensis" aspiration for 10 long years.
METHODS: A case was reported that a female patient complained of a 10-year
history of productive cough. A battery of tests were given to confirm the
diagnosis. RESULTS: Chest computed tomography (CT) showed extensive
bronchiectasis and multiple nodules, along with stenosis of left lower lobar
bronchus. An extensive solid lesion with surrounding inflammatory granulation
tissue was seen on her first bronchoscopy and biopsy revealed chronic mucosal
inflammation. A neglected history of Coptis chinensis regularly kept in-mouth
while sleeping for the last 10 years in this patient provided clues for a final
diagnosis. Confirmatory diagnosis of bilateral tracheobronchial foreign bodies
caused by recurrent inhalation of Coptis chinensis was made by a second
bronchoscopy. CONCLUSIONS: This case clearly demonstrates that a precise medical
history is often overlooked. A high index of suspicion, a precise medical
history, radiographic features of chronic respiratory symptoms not explained by
other conditions were keys to diagnosing this case.
PMID- 27495018
TI - The adoption of the Reference Framework for diabetes care among primary care
physicians in primary care settings: A cross-sectional study.
AB - The prevalence of diabetes mellitus has been increasing both globally and
locally. Primary care physicians (PCPs) are in a privileged position to provide
first contact and continuing care for diabetic patients. A territory-wide
Reference Framework for Diabetes Care for Adults has been released by the Hong
Kong Primary Care Office in 2010, with the aim to further enhance evidence-based
and high quality care for diabetes in the primary care setting through wide
adoption of the Reference Framework.A valid questionnaire survey was conducted
among PCPs to evaluate the levels of, and the factors associated with, their
adoption of the Reference Framework.A total of 414 completed surveys were
received with the response rate of 13.0%. The average adoption score was 3.29 (SD
0.51) out of 4. Approximately 70% of PCPs highly adopted the Reference Framework
in their routine practice. Binary logistic regression analysis showed that the
PCPs perceptions on the inclusion of sufficient local information (adjusted odds
ratio [aOR] = 4.748, 95%CI 1.597-14.115, P = 0.005) and reduction of professional
autonomy of PCPs (aOR = 1.859, 95%CI 1.013-3.411, P = 0.045) were more likely to
influence their adoption level of the Reference Framework for diabetes care in
daily practices.The overall level of guideline adoption was found to be
relatively high among PCPs for adult diabetes in primary care settings. The
adoption barriers identified in this study should be addressed in the continuous
updating of the Reference Framework. Strategies need to be considered to enhance
the guideline adoption and implementation capacity.
PMID- 27495019
TI - Widespread pain and depression are key modifiable risk factors associated with
reduced social participation in older adults: A prospective cohort study in
primary care.
AB - In older adults, reduced social participation increases the risk of poor health
related quality of life, increased levels of inflammatory markers and
cardiovascular disease, and increased mortality. Older adults frequently present
to primary care, which offers the potential to deliver interventions at the point
of care to increase social participation. The aim of this prospective study was
to identify the key modifiable exposures that were associated with reduced social
participation in a primary care population of older adults.The study was a
population-based prospective cohort study. Participants (n = 1991) were those
aged >=65 years who had completed questionnaires at baseline, and 3 and 6-year
follow-ups. Generalized linear mixed modeling framework was used to test for
associations between exposures and decreasing social participation over 6
years.At baseline, 44% of participants reported reduced social participation,
increasing to 49% and 55% at 3 and 6-year follow-up. Widespread pain and
depression had the strongest independent association with reduced social
participation over the 6-year follow-up period. The prevalence of reduced social
participation for those with widespread pain was 106% (adjusted incidence rate
ratio 2.06, 95% confidence interval 1.72, 2.46), higher than for those with no
pain. Those with depression had an increased prevalence of 82% (adjusted
incidence rate ratio 1.82, 95% confidence interval 1.62, 2.06). These
associations persisted in multivariate analysis.Population ageing will be
accompanied by increasing numbers of older adults with pain and depression.
Future trials should assess whether screening for widespread pain and depression,
and targeting appropriate treatment in primary care, increase social
participation in older people.
PMID- 27495020
TI - Effect of prenatal and postnatal malnutrition on intellectual functioning in
early school-aged children in rural western China.
AB - The aim of this study was to evaluate the effect of prenatal and postnatal
malnutrition on the intellectual functioning of early school-aged children. We
followed the offspring of women who had participated in a trial of prenatal
supplementation with different combinations of micronutrients and who remained
resident in the study field. We measured their intellectual functioning using the
Wechsler intelligence scale for children (WISC-IV). Height-for-age, weight-for
age, and body mass index (BMI)-for-age were used as anthropometric nutritional
status indices. Four of the 5 composite scores derived from the WISC-IV, except
for working memory index (WMI), were significantly lower in low birth weight
children after adjusting for confounds. All 5 composite scores, including full
scale intelligence quotient (FSIQ), verbal comprehension index (VCI), WMI,
perceptual reasoning index (PRI), and processing speed index (PSI) were
significant lower in stunted and underweight children. The differences in the
means of WISC-IV test scores were greatest between stunted and nonstunted
children. The means for FSIQ, VCI, WMI, PRI, and PSI were as follows: 5.88 (95%
confidence interval [CI]: 2.84-8.92), 5.08 (95% CI: 1.12-8.41), 4.71 (95% CI:
1.78-7.66), 6.13 (95% CI: 2.83-9.44), and 5.81 (95% CI: 2.61-9.00). These means
were lower in stunted children after adjusting for confounds. Our results suggest
the important influences of low birth weight and postnatal malnutrition
(stunting, low body weight) on intellectual functioning in early school-aged
children.
PMID- 27495021
TI - Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung
cancer (NSCLC) treated with target therapy: Result from 3 clinical trials of
advanced NSCLC by 1 institution.
AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are
used as standard therapies for advanced nonsmall cell lung cancer (NSCLC)
patients with EGFR mutation positive. Because these targeted therapies could
cause tumor necrosis and shrinkage, the purpose of the study is to search for a
value of optimal tumor shrinkage as an appropriate indicator of outcome for
advanced NSCLC.A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA
registration clinical trial, TRUST study and ZD6474 study), who received
Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD),
respectively, during December 2003 and October 2007, were retrospectively
analyzed. The response evaluation criteria in solid tumors (RECIST) were used to
identify responders, who had complete response (CR) or partial responses (PR) and
nonresponders who had stable disease (SD) or progressive disease (PD). Receiver
operating characteristics (ROC) analysis was used to find the optimal tumor
shrinkage as an indicator for tumor therapeutic outcome. Univariate and
multivariate Cox regression analyses were performed to compare the progression
free survival (PFS) and overall survival (OS) between responders and
nonresponders stratified based on radiologic criteria.Among the 88 NSCLC
patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC
indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor
diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46
responders (<=8.32%) and 42 nonresponders (>=8.32%). Univariate and multivariate
Cox regression analyses indicated that (1) the responders (<=8.32%) and
nonresponders (>= -8.32%) were significantly different in median PFS (13.40 vs
1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) -8.32%
in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11,
95% CI, 3.75 to 17.51, P < 0.001) and OS (HR, 2.36, 95% CI, 1.41 to 3.96, P =
0.001).However, 8.32% tumor diameter shrinkage is validated as a reliable outcome
predictor of advanced NSCLC patients receiving EGFR-TKIs therapies and may
provide a practical measure to guide therapeutic decisions.
PMID- 27495022
TI - Prevalence and impact of Clostridium difficile infection in elderly residents of
long-term care facilities, 2011: A nationwide study.
AB - The elderly population is particularly vulnerable to Clostridium difficile
infection (CDI), but the epidemiology of CDI in long-term care facilities (LTCFs)
is unknown.We performed a retrospective cohort study and used US 2011 LTCF
resident data from the Minimum Data Set 3.0 linked to Medicare claims. We
extracted CDI cases based on International Classification of Diseases-9 coding,
and compared residents with the diagnosis of CDI to those who did not have a CDI
diagnosis during their LTCF stay. We estimated CDI prevalence rates and
calculated 3-month mortality rates.The study population consisted of 2,190,613
admissions (median age 82 years; interquartile range 76-88; female to male ratio
2:1; >80% whites), 45,500 of whom had a CDI diagnosis. The nationwide CDI
prevalence rate was 1.85 per 100 LTCF admissions (95% confidence interval [CI]
1.83-1.87). The CDI rate was lower in the South (1.54%; 95% CI 1.51-1.57) and
higher in the Northeast (2.29%; 95% CI 2.25-2.33). Older age, white race,
presence of a feeding tube, unhealed pressure ulcers, end-stage renal disease,
cirrhosis, bowel incontinence, prior tracheostomy, chemotherapy, and chronic
obstructive pulmonary disease were independently related to "high risk" for CDI.
Residents with a CDI diagnosis were more likely to be admitted to an acute care
hospital (40% vs 31%, P < 0.001) and less likely to be discharged to the
community (46% vs 54%, P < 0.001) than those not reported with CDI during stay.
Importantly, CDI was associated with higher mortality (24.7% vs 18.1%, P =
0.001).CDI is common among the elderly residents of LTCFs and is associated with
significant increase in 3-month mortality. The prevalence is higher in the
Northeast and risk stratification can be used in CDI prevention policies.
PMID- 27495023
TI - A telemedicine wound care model using 4G with smart phones or smart glasses: A
pilot study.
AB - To assess the feasibility of a wound care model using 4th-generation mobile
communication technology standards (4G) with smart phones or smart glasses for
wound management.This wound care model is an interactive, real-time platform for
implementing telemedicine changing wound dressings, or doing operations. It was
set up in March 2015 between Jinhua in Zhejiang province and Shanghai, China,
which are 328 km apart. It comprised of a video application (APP), 4G net, smart
phones or smart glasses, and a central server.This model service has been used in
30 patients with wounds on their lower extremities for 109 times in 1 month.
Following a short learning curve, the service worked well and was deemed to be
user-friendly. Two (6.7%) patients had wounds healed, while others still required
wound dressing changes after the study finished. Both local surgeons and patients
showed good acceptance of this model (100% and 83.33%, respectively).This
telemedicine model is feasible and valuable because it provides an opportunity of
medical service about wound healing in remote areas where specialists are scarce.
PMID- 27495024
TI - Variability in the lymph node retrieval after resection of colon cancer:
Influence of operative period and process.
AB - The purpose of this study was to evaluate variations in the number of retrieved
lymph nodes (LNs) over time and to determine the factors that influence the
retrieval of <12 LNs during colon cancer resection.Patients with colon cancer who
were surgically treated between 1997 and 2013 were identified from our
institutional tumor registry. Patient, tumor, and pathologic variables were
evaluated. Factors that influenced the retrieval of <12 LNs were evaluated using
multivariate logistic regression modeling, including time effects.In total, 6967
patients were identified. The median patient age was 61 years (interquartile
range [IQR] = 45-79 years) and 58.4% of these patients were male. The median
number of LNs retrieved was 21 (IQR = 14-29), which increased from 14 (IQR = 11
27) in 1997 to 26 (IQR = 19-34) in 2013. The proportion of patients with >=12
retrieved LNs increased from 72% in 1997 to 98.8% in 2013 (P < 0.00001). This
corresponded to the more recent emphasis on a multidisciplinary approach to
adequate LN evaluation. The number of retrieved LNs was also found to be
associated with age, sex, tumor location, T stage, and operative year. Tumor
location and T stage influenced the number of retrieved LNs, irrespective of the
operative year (P < 0.05). Factors including a tumor location in the sigmoid/left
colon, old age, open resection, earlier operative year, and early T stage were
more likely to be associated with <12 recovered LNs (P < 0.5; chi-squared test)
(P < 0.001).The total number of retrieved LNs may be influenced by tumor location
and T stage of a colon cancer, irrespective of the year of surgery. LN retrieval
after colon cancer resection has increased in recent years due to a better
awareness of its importance and the use of multidisciplinary approaches.
PMID- 27495025
TI - Short-term family-centered workshop for children with developmental delays
enhances family functioning and satisfaction: A prospective clinical trial.
AB - We investigated the clinical efficacy on family functioning and parental
satisfaction of a short-term family-centered workshop for children with
developmental delays.A total of 32 children with developmental delays and their
parents participated in 2-hour weekly group therapy sessions over 6 weeks. The
workshop was conducted by rehabilitation professionals and teachers using a
family-centered multidisciplinary approach. Both before and after the 6-week
workshop, the parents were administered the Pediatric Quality of Life Inventory
(PedsQL) Family Impact Module, the PedsQL Healthcare Satisfaction Module, the
Hospital Anxiety and Depression Scale, and the World Health Organization Quality
of Life brief assessment instrument. Overall satisfaction with the workshop was
also evaluated.Significant improvements were noted in physical aspect (P = 0.03),
communication (P = 0.002), and daily activities (P = 0.04) in the PedsQL Family
Impact Module, and in communication (P = 0.03) and technical skills (P = 0.05) in
the PedsQL Healthcare Satisfaction Module. Overall satisfaction with the workshop
was rated as very high. There was no significant effect on psychological distress
or quality of life.Short-term family-centered workshops for children with
developmental delays improved family functioning and the parental perception of
satisfaction, including health care satisfaction.
PMID- 27495026
TI - HBV is a risk factor for poor patient prognosis after curative resection of
hepatocellular carcinoma: A retrospective case-control study.
AB - Controversy exists regarding pathological factors affecting the prognosis of
hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV-HCC). Their
postoperative clinical behaviors and the exact HBV Deoxyribonucleic Acid (DNA)
thresholds that distinguish good and poor prognoses are unknown. This study aimed
to compare clinicopathological, pre- and postoperative clinical factors and
overall and recurrence-free survival (RFS) between HBV-HCC patients and
nonhepatitis B and nonhepatitis C HCC (NBC-HCC) patients to determine the optimal
prognostic HBV DNA threshold.Data from 1440 patients with HBV-HCC and NBC-HCC who
underwent curative hepatectomy were retrospectively analyzed.Liver function in
the HBV-HCC group was significantly worse than in the NBC-HCC group. Compared
with NBC-HCC patients, HBV-HCC patients had significantly more vascular invasion
and advanced HCC. The HBV-HCC patients also had significantly worse liver
function and more complications. Further survival analysis showed significantly
lower overall and RFS rates and a higher early recurrence rate in the HBV-HCC
group. Univariate analysis indicated that HBV was a risk factor for overall and
RFS. Finally, X-tile analysis revealed that the optimal HBV DNA cutoff points for
predicting RFS and overall survival in HCC patients were 10,100 and 12,800 IU/mL,
respectively.After hepatectomy for HCC, HBV-HCC patients had more complications
and a worse prognosis than NBC-HCC patients. Antiviral therapy should be
considered before hepatectomy in patients with high (more than approximately 10
IU/mL) HBV DNA levels.
PMID- 27495027
TI - Polymorphism in the IL4R gene and clinical features are associated with glioma
prognosis: Analyses of case-cohort studies.
AB - Inflammatory gene polymorphisms may be associated with glioma risk. The purpose
of this study was to analyze effects of certain inflammatory gene and some
clinical factors on patient survival.The clinical information of 269 glioma
patients conceived operation from September 2010 to May 2014 to decide the 1-, 3
year survival rates according to follow-up results and analyze age, gender, the
WHO classification, extent of surgical resection, radiotherapy and chemotherapy
factors effects on prognosis. Survival distributions were estimated by using the
Kaplan-Meier method and difference in the survival was tested using the log-rank
test. To estimate the association between the IL4, IL13, IL10, IL4R SNPs, and PFS
and OS in glioma, the HR and 95% CI were calculated by univariate Cox
proportional hazards model. Multivariate Cox model were performed to compute
adjusted HR and 95% CI. All data was analyzed with SPSS17.0 package. Extent of
surgical resection, chemotherapy, and age are an important factor in glioma
overall survival and progression-free survival overall. Extent of surgery and
chemotherapy are important factors in astrocytoma overall survival. Univariate
analysis showed that IL4R rs1801275 was significantly associated with overall
survival of glioma and astrocytoma patients (P < 0.05). Multivariate Cox
regression analysis showed that IL4R rs1801275 GG genotype could increase the
death risk of glioma and astrocytoma patients (Glioma: hazard ratio [HR]: 4.897,
95% confidence limits [95% CI]: 1.962-12.222, P = 0.001; Astrocytoma: HR: 15.944,
95% CI: 4.019-63.253, P < 0.05).Our research results showed that extent of
surgical resection, age, and chemotherapy affect the prognosis of glioma. The
IL4R gene may affect the survival of glioma patients.
PMID- 27495028
TI - Small intestine contrast ultrasonography for the detection and assessment of
Crohn disease: A meta-analysis.
AB - BACKGROUND: Crohn disease (CD) is a chronic relapsing disease. Imaging modalities
are essential for the diagnosis and assessment of CD. Small intestine contrast
ultrasonography (SICUS) is a well-tolerated, noninvasive and radiation-free
modality and has shown potential in CD assessment. We aimed at evaluating the
diagnostic accuracy of SICUS in the detection and assessment of small-bowel
lesions and complications in CD. METHODS: We searched PubMed database for
relevant studies published before April 24, 2016. We integrated the true
positive, false positive, false negative, and true negative into the pooled
estimates of sensitivity, specificity, positive likelihood ratio, negative
likelihood ratio, and diagnostic odds ratio. Forest plots were to represent the
pooled results of all studies. RESULTS: Thirteen articles were finally considered
eligible. The pooled sensitivity and specificity of SICUS in detecting small
bowel lesions were 0.883 (95% confidence interval (CI) 0.847-0.913) and 0.861
(95% CI 0.828-0.890), respectively. The pooled diagnostic odds ratio was 39.123
(95% CI 20.014-76.476) and the area under the curve of summary receiver operating
characteristic was 0.9273 (standard error: 0.0152). In subgroup analyses, SICUS
represented fine sensitivity and specificity in proximal and distal small
intestine lesion, as well as in CD-related complications such as stricture,
dilation, abscess, and fistula. CONCLUSION: SICUS is accurate enough to make a
complete assessment about the location, extent, number, and almost all kinds of
complications in CD small-bowel lesions.
PMID- 27495029
TI - Clinical characteristics and prognostic factors of primary gastric lymphoma: A
retrospective study with 165 cases.
AB - Primary gastric lymphoma (PGL) is the most common extranodal non-Hodgkin
lymphoma. This retrospective study aimed to analyze the clinical characteristics,
prognostic factors, and roles of different treatment modalities in patients with
PGL.From January 2003 to November 2014, 165 patients who were diagnosed with PGL
at West China Hospital were enrolled in this study. The clinical features,
treatment, and follow-up information were analyzed.In this study, diffuse large B
cell lymphoma (DLBCL) (108, 65.5%) and mucosa-associated lymphoid tissue (MALT)
lymphoma (52, 31.5%) were two predominant histological subtypes. One-year and 5
year overall survival (OS) rates of all patients were 95.2% and 79.5%,
respectively; in whom 110 (66.7%) underwent surgery, 110 (66.7%) received
chemotherapy, 12 (7.3%) received radiotherapy, and 10 (6.1%) received
Helicobacter pylori eradication. And 75 patients (45.5%) were treated with at
least 2 different types of therapies. Elevated lactic dehydrogenase (LDH) levels,
poor performance status (PS), advanced stage, International Prognostic Index
(IPI) score >=3, conservative treatment, and high-grade histological subtype were
associated with worse prognosis in univariate analysis. Cox regression analysis
showed that LDH levels, PS, staging, and histological subtype were independent
predictors of survival outcomes. In the DLBCL type, 5-year OS was significantly
better in the surgically treated group (80.1%) than that of patients
conservatively treated (49.8%) (P = 0.001). Surgical treatment had almost no
impact on OS in the MALT type than conservative treatment (P = 0.597). The
proportion of patients received conservative treatment increased from 4.5% in
period 1 to 51.7% in period 4.High LDH levels, poor PS, advanced staging, and
malignant pathological type at diagnosis are significantly associated with poor
OS. Our data suggest that surgery is superior in prognosis over conservative
treatment in the DLBCL type, but not in the MALT type. Recently, conservative
treatment is becoming more preferred approach in patients with PGL.
PMID- 27495030
TI - Hormone replacement therapy benefits meibomian gland dysfunction in
perimenopausal women.
AB - Meibomian gland dysfunction (MGD) is believed to be the leading cause of dry eye
(DE) disease worldwide. The connection between aging and MGD has long been
recognized. However, few studies have addressed the relationship between MGD and
hormone replacement therapy (HRT) in perimenopausal women, and not have examined
the prevalence of MGD in perimenopausal women. The purpose of this study was to
address and evaluate the possible relationship between MGD and HRT in
perimenopausal women.The results suggest that perimenopausal women have a high
prevalence of DE related to perimenopausal symptoms. The study also shows that
perimenopausal women who use HRT can gain benefits for DE as well as for
perimenopausal symptoms. Physicians caring for women who are experiencing DE
related to perimenopausal symptoms should consider HRT.
PMID- 27495031
TI - Evaluation of left and right ventricular myocardial function after lung resection
using speckle tracking echocardiography.
AB - The impact of major lung resections on myocardial function has not been well
investigated. We aimed to identify this impact through the use of speckle
tracking echocardiography (STE) to evaluate the right and left ventricular
myocardial function in patients who underwent lung resections.Thirty patients who
had lung resections were recruited for this study. Ten patients who underwent
pneumonectomies were matched by age and sex, with 20 patients who underwent
lobectomies. STE was performed on both right and left ventricle (RV and LV).
Strain values of pre and postlung resections were compared in both the
pneumonectomy group and the lobectomy group. Comparison between the pneumonectomy
group and the lobectomy group was also studied.Left ventricular ejection fraction
remained normal (>55%), but significantly decreased after lung resection in both
the pneumonectomy group and the lobectomy group. An accelerated heart rate was
observed in both groups after lung resection, with the pneumonectomy group
demonstrating extra rapid heart rate (P < 0.05). Strain values in the RV and LV
decreased in both groups after lung resection, with the pneumonectomy group
exhibiting a further decrease in longitudinal strain in LV and RV when compared
with the lobectomy group (P < 0.05).Right and left ventricular dysfunction can
occur after lung resection regardless of pneumonectomy or lobectomy, and
lobectomy may have a less significant impact on myocardial functions. This study
demonstrated that STE is able to detect acute cardiac dysfunction after lung
resection.
PMID- 27495032
TI - The link between chronic rhinosinusitis and asthma: A questionnaire-based study.
AB - Treatments for chronic rhinosinusitis (CRS) and asthma can affect both
conditions, based on the united airway concept. This study aimed to evaluate the
link between CRS and asthma, based on disease-specific quality of life
measures.We performed a prospective cohort study to investigate the correlations
between results from CRS- and asthma-specific questionnaires. Thirty-two patients
with asthma and CRS were evaluated before and after undergoing nasal surgery at a
tertiary medical center.There were significant correlations between the results
from the Asthma Control Test (ACT) and the Sino-Nasal Outcome Test-22, as well as
between the results of the ACT and Rhinoconjunctivitis Quality of Life
Questionnaire, at both the preoperative and 3-month postoperative evaluations (P
< 0.01). Moreover, nasal surgery improved the sinonasal symptoms, asthma control,
and pulmonary function (P < 0.01).Increasingly severe sinonasal symptoms of CRS
were associated with poor asthma control. Therefore, CRS and asthma should be
considered and treated as common airway diseases.
PMID- 27495033
TI - A simple prognostic score system predicts the prognosis of solitary large
hepatocellular carcinoma following hepatectomy.
AB - Solitary large hepatocellular carcinomas (SLHCC) form a heterogeneous group of
patients with different survival probabilities. The aim of our study was to
develop a simple prognostic index for identifying prognostic subgroups of SLHCC
patients.A retrospective analysis of clinical data from 268 patients with
operable SLHCC was conducted to investigate prognostic factors and to construct a
score system based on risk factors. A Cox proportional hazard regression analysis
was used to evaluate the variables associated with prognosis. Survival analyses
were performed using Kaplan-Meier survival curves.Three variables remained in the
final multivariate model: platelet to lymphocyte ratio (PLR), microvascular
invasion (MVI), and tumor size with hazard ratios equal to 1.004 (95% confidence
interval: 1.001-1.006), 1.092 (1.044-1.142), and 2.233 (1.125-2.233),
respectively. A score of 1 was assigned to each risk factor. Patient scores were
determined based on these risk factors; thus, the scores ranged between 0 and 3.
Ultimately, three categories (0, 1-2, 3) were defined. Patients with scores of 3
had a 5-year survival rate of 25.4%, whereas patients with a score of 0 had a 5
year survival rate of 52.1%. The prognosis significantly worsened as the score
increased. Similar results were found among cirrhotic and noncirrhotic
patients.Our simple prognostic index successfully predicts SLHCC survival.
PMID- 27495034
TI - Progression-free and overall survival in metastatic castration-resistant prostate
cancer treated with abiraterone acetate can be predicted with serial C11-acetate
PET/CT.
AB - In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)
acetate positron emission tomography/computed tomography (PET/CT) to assess
response in patients with metastatic castration-resistant prostate cancer (mCRPC)
treated with abiraterone acetate (AA).A total of 30 patients with mCRPC were
monitored with C11-acetate PET/CT and PSA levels during their treatment with AA.
Retrospective evaluation of their response was made after 102 days (median; range
70-155) of treatment. Statistical analyses were employed to detect predictors of
progression-free survival (PFS) and overall survival (OS), and potential
correlation between serum levels of PSA, standardized uptake values (SUVpeak),
and bone lesion index measured from PET were investigated.At follow-up 10
patients exhibited partial response (PR), 10 progressive disease (PD), and 10
stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD
were significantly associated with PFS and OS. CT response was also associated
with OS, but only 19/30 patients demonstrated a lesion meeting target lesion
criteria according to RECIST 1.1. No PET/CT baseline characteristic was
significantly associated with PFS or OS. A PSA response (reduction in the level
by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response,
those with PD had significantly shorter OS than those with PR or SD.PFS and OS in
patients with mCRPC treated with AA can be predicted from repeated C11-acetate
PET/CT. This may be of particular clinical value in patients who do not exhibit a
PSA response to treatment.
PMID- 27495035
TI - Risk factors associated with postcraniotomy meningitis: A retrospective study.
AB - Postcraniotomy meningitis (PCM) is a major challenge in neurosurgery, and
changing patterns of infectious agents in PCM have been noted. The limited
epidemiological data and urgent clinical needs motivated this research. We
conducted this study to determine a risk assessment for PCM and the current
pattern of infectious agents.We performed a retrospective case-control study of
significant cases of postcraniotomy meningitis in the Changhua Christian Hospital
System between January 1, 2008, and December 31, 2012. Postcraniotomy meningitis
was diagnosed in 22 out of 4392 surgical patients; this data was reviewed for
risk assessment.This study assessed the risk factors for postcraniotomy
meningitis and found that it was more frequently seen in patients who were
elderly (OR = 1.57, 95% CI = 1.32-2.98, P = 0.013), underwent emergency
procedures (OR = 4.82, 95% CI = 1.50-14.53, P = 0.008), had leak of cerebrospinal
fluid (OR = 4.62, 95% CI = 2.03-10.50, P = 0.012), had external ventricular
drainage (OR = 4.68, 95% CI = 2.46-8.87, P = 0.006), were admitted to the
intensive care unit (OR = 2.41, 95% CI = 1.53-8.08, P = 0.012), had used drain
placement >72 hours (OR = 2.66, 95% CI = 1.04-4.29, P = 0.007), had surgery >4.5
hours (OR = 2.38, 95% CI = 1.39-4.05, P = 0.005), had repeat operations (OR =
2.74, 95% CI = 1.31-5.73, P = 0.018), endured trauma (OR = 5.97, 95% CI = 1.57
17.61, P = 0.007), or had 30-days mortality (OR = 5.07, 95% CI = 2.20-11.48, P =
0.001). The predominant pathogens isolated from cerebrospinal fluid were
Staphylococcus aureus in 8 patients (36.7%) and Acinetobacter baumannii in 7
patients (31.8%). In our study, the mortality rate was 5.1% among all
postcraniotomy patients.Accurate risk assessment, early diagnosis, and choice of
appropriate antibiotics in accordance with epidemiologic information are the
cornerstones of reducing mortality and morbidity in PCM. The changing pattern of
infectious agents in PCM over time suggests the necessity of further studies to
provide the most up-to-date insight to physicians.
PMID- 27495036
TI - Can eculizumab be discontinued in aHUS?: Case report and review of the
literature.
AB - BACKGROUND: The management of atypical hemolytic uremic syndrome (aHUS) has
evolved into better control of thrombotic microangiopathy (TMA) and recovery of
renal functions since the recent introduction of the terminal complement cascade
blocker, eculizumab, into clinical use. Better characterization of genotype
phenotype relations has become possible with genetic and clinical studies.
However, these advances brought up some important issues, such as the possibility
and timing of discontinuation of eculizumab and strategy of follow-up that need
to be enlightened. CASE SUMMARY: One of our aHUS cases with a novel complement
factor H mutation, who developed unusual laboratory findings (thrombocytopenia
and mild creatinine elevation without other features of TMA) following
discontinuation of eculizumab was presented. Literature and case reports relevant
to discontinuation of eculizumab in aHUS patients were reviewed. CONCLUSION:
Limited experience suggests that the risk of recurrence of TMA following
discontinuation of eculizumab is relatively low for patients with MCP mutations,
homozygous CFHR3/R1 deletions, anti-CFH antibodies, CFI mutations, and no
identifiable mutations, whereas there is a major risk for patients with CFH
mutations. Early detection of TMA recurrence and prompt retreatment with
eculizumab seem to be efficient in controlling of TMA and restoration of kidney
functions.
PMID- 27495037
TI - Radiation-induced nausea and vomiting: Is ABO blood group as important as
radiation and patient-related factors? An observational study.
AB - Despite the improvements in cancer screening and treatment, it still remains as
one of the leading causes of mortality worldwide. Nausea and vomiting as the side
effects of different cancer treatment modalities, such as radiotherapy, are
multifactorial and could affect the treatment continuation and patient quality of
life. Therefore, the aim of this study was to assess the possible linkage between
ABO blood groups and radiation-induced nausea and vomiting (RINV), also its
incidence and affecting factors.One hundred twenty-eight patients referring to
Tohid hospital of Sanandaj, Iran, were selected and the patients and treatment
related factors were determined in a cross-sectional study. Patients' nausea and
vomiting were recorded from the onset of treatment until 1 week after treatment
accomplishment. Also, previous possible nausea and vomiting were recorded. The
frequencies of nausea and vomiting and their peak time were examined during the
treatment period.The association between ABO blood group and the incidence of
radiotherapy-induced nausea and vomiting (RINV) were significant and it seems
that A blood group patients are the most vulnerable individuals to these
symptoms. The association between Rhesus antigen and the time of maximum severity
of RINV may indicate that Rhesus antigen affects the time of maximum severity of
RINV. The incidence of RINV was not affected by karnofsky performance status, but
it was related to the severity of RINV. Furthermore, among the factors affecting
the incidence of nausea and vomiting, nausea and vomiting during patient's
previous chemotherapy, radiotherapy region, and background gastrointestinal
disease were shown to be three important factors.In addition to familiar RINV
affecting factors, ABO blood group may play an important role and these results
address the needs for further studies with larger sample size.
PMID- 27495038
TI - The relative effect of mammographic screening on breast cancer mortality by
socioeconomic status.
AB - Breast cancer incidence and mortality are higher in women with a high
socioeconomic status (SES). The potential to prevent death from breast cancer is
therefore greater in the high SES group. This does, however, require that the
effectiveness of screening in the high SES group is equal to or greater than the
effectiveness in the low SES group. The aim of this study is to assess the
relative effectiveness of mammographic screening on breast cancer mortality by
SES.In Nijmegen, the Netherlands, women are invited to participate in biennial
mammographic screening since 1975. Postal code is collected at each round and is
used to calculate the SES of each woman based on the SES indicator of the
Netherlands Institute for Social Research. The Dutch average was used to classify
the SES score of each woman as either high or low. We designed a case-control
study to investigate the effect of mammographic screening in women aged 50 to 75,
40 to 75, and 50 to 69 years, and calculated the odds ratios (ORs) and 95%
confidence intervals (CIs).Among the women invited to the mammographic screening
program in Nijmegen, 10% had a high SES. In women aged 50 to 75 years, the breast
cancer death rate was 38% lower in screened women than in unscreened women. The
ORs for women with high SES (OR 0.82, 95% CI 0.31-2.19) and low SES did not
differ significantly (OR 0.61, 95% CI 0.47-0.78).Mammographic screening reduces
breast cancer mortality, but we did not observe a significant difference in the
relative effectiveness of screening by SES. If the effectiveness of mammographic
screening is indeed not dependent on SES status, the absolute number of breast
cancer deaths prevented by mammographic screening will be greater in the high SES
than low SES group, because women with a high SES have a greater risk of breast
cancer death.
PMID- 27495039
TI - Metabolic syndrome is associated with increased risk of Barrett esophagus: A meta
analysis.
AB - BACKGROUND: Barrett esophagus (BE) is considered precursor condition of
esophageal adenocarcinoma. Its incidence and prevalence are increasing in general
population. Studies reported that metabolic syndrome (MS) or diabetes mellitus
(DM) is related to increased risk of BE. Current study was to assess and better
understand the relationship between MS /DM and BE. METHODS: Electronic search was
conducted in the database Pubmed/Medline (-December, 2015), Embase (-December,
2015), Cochrane Library (-December, 2015), and Web of Knowledge (-December,
2015). Studies included were assessed with summary odds ratios (ORs) with 95%
confidence intervals (CIs) and compared exposure group with control group. The
heterogeneity was examined by the funnel plot and the Egger's test. Subgroup
analyses and sensitive analyses were performed for the detection of possible
heterogeneity and impact on stability of analysis results. RESULTS: Twelve
publications met the criteria and included 355,311 subjects were analyzed. The
pooled results showed MS was closely associated with increased risk of BE (OR =
1.23; 95%CI 1.03-1.47; P = 0.024), and yet DM did not significantly increase the
risk of BE (OR = 1.07; 95%CI 0.82-1.38; P = 0.627). Substantial heterogeneities
were detected. No significant publication bias was detected by Egger's test (P =
0.23). CONCLUSIONS: Based on the results of current meta-analysis, MS is
associated with increased risk of BE. Further long-term follow-up prospective
study needs to verify the current results, and definite pathophysiological
mechanism needs to be further investigated and clearly elucidated.
PMID- 27495040
TI - Therapeutic role of hyperinsulinemia/euglycemia in aluminum phosphide poisoning.
AB - BACKGROUND: Different protocols have been suggested to treat aluminum phosphide
(ALP) poisoning. We aimed to evaluate the possible therapeutic effect of
hyperinsulinemia/euglycemia (HIE) in treatment of ALP poisoning. METHODS: In a
prospective interventional study, a total of 88 ALP-poisoned patients were
included and assigned into HIE group undergoing glucose/insulin/potassium (GIK)
protocol and a control group that was managed by routine conventional treatments.
The 2 groups were then compared regarding the signs and symptoms of toxicity and
their progression, development of complications, and final outcome to detect the
possible effect of GIK protocol on the patients' course of toxicity and outcome.
RESULTS: The 2 groups were similar in terms of demographic characteristics and on
arrival vital signs and lab tests. Using GIK protocol resulted in significantly
longer hospital stays (24 vs 60 hours; P < 0.001) and better outcomes (72.7% vs
50% mortality; P = 0.03). Regression analysis showed that GIK duration was an
independent variable that could prognosticate mortality (odds ratio [95%
confidence interval] = 1.045 [1.004,1.087]). The risk of mortality decreased by
4.5% each hour after initiation of GIK. CONCLUSION: GIK protocol improves the
outcome of ALP poisoning and increases the length of hospital stay.
PMID- 27495041
TI - Correlation between ambulatory function and clinical factors in hemiplegic
patients with intact single lateral corticospinal tract: A pilot study.
AB - To define the relationship between the complete destruction of 1 lateral
corticospinal tract (CST), as demonstrated by diffusion tensor imaging (DTI)
tractography, and ambulatory function 6 months following stroke.Twenty-six adults
(17 male, 9 female) with poststroke hemiplegia who were transferred to the
physical medicine and rehabilitation department. Participants underwent DTI
tractography, which showed that 1 lateral CST had been clearly
destroyed.Functional ambulation classification (FAC) scores at admission,
discharge, and 6 months after discharge were used to evaluate the patients'
ability to walk. The National Institutes of Health Stroke Scale (NIHSS) and the
Korean version of the modified Barthel index (K-MBI) at admission, discharge, and
6 months after discharge were used to evaluate the degree of functional
recovery.Of the 26 patients, 18 were nonambulatory (FAC level 1-3), and 8 were
able to walk without support (FAC level 4-6). The type of stroke (infarction or
hemorrhage), site of the lesion, spasticity of lower extremities, cranioplasty,
and the time taken from onset to MRI were not statistically significantly
correlated with the ability to walk. However, statistically significant
correlations were found in relation to age, K-MBI scores, and initial NIHSS
scores.Despite the complete damage to the lesion site and the preservation of 1
unilateral CST, as shown by DTI, good outcomes can be predicted on the basis of
younger age, low NIHSS scores, and high MBI scores at onset.
PMID- 27495042
TI - Significant partial response of metastatic intra-abdominal and pelvic round cell
liposarcoma to a small-molecule VEGFR-2 tyrosine kinase inhibitor apatinib: A
case report.
AB - INTRODUCTION: Myxoid/round cell liposarcoma is the second most common subtype of
liposarcoma. Chemotherapy and radiotherapy have a limited efficacy for treating
advanced myxoid/round cell liposarcoma, with relatively serious side effects.
CASE PRESENTATION: We herein present a 68-year-old Chinese woman initially
diagnosed with advanced multiple intra-abdominal and pelvic round cell
liposarcoma.She refused to receive cytotoxic chemotherapy and received apatinib
as the first-line therapy, a novel tyrosine kinase inhibitor of vascular
endothelial growth factor receptor-2 that has been used in the treatment of
patients with metastatic gastric cancer who progressed with 2 or more
chemotherapy regimens. This patient was partially responsive to apatinib with a
dose of 500 mg daily. No serious drug-related side effects were observed.
CONCLUSION: Our findings indicate that some cases of liposarcoma may be
responsive to antiangiogenic agent apatinib. Randomized clinical studies are
needed to further confirm the efficacy and safety of apatinib in the clinical
treatment of liposarcoma.
PMID- 27495043
TI - Does surgery for instability of the shoulder truly stabilize the glenohumeral
joint?: A prospective comparative cohort study.
AB - Despite the fact that surgery is commonly used to treat glenohumeral instability,
there is no evidence that such treatment effectively corrects glenohumeral
translation. The purpose of this prospective clinical study was to analyze the
effect of surgical stabilization on glenohumeral translation.Glenohumeral
translation was assessed in 11 patients preoperatively and 1 year postoperatively
following surgical stabilization for anterior shoulder instability. Translation
was measured using optical motion capture and computed tomography.Preoperatively,
anterior translation of the affected shoulder was bigger in comparison to the
normal contralateral side. Differences were significant for flexion and abduction
movements (P < 0.001). Postoperatively, no patients demonstrated apprehension and
all functional scores were improved. Despite absence of apprehension,
postoperative anterior translation for the surgically stabilized shoulders was
not significantly different from the preoperative values.While surgical treatment
for anterior instability limits the chance of dislocation, it does not seem to
restore glenohumeral translation during functional range of motion. Such
persistent microinstability may explain residual pain, apprehension, inability to
return to activity and even emergence of dislocation arthropathy that is seen in
some patients. Further research is necessary to better understand the causes,
effects, and treatment of residual microinstability following surgical
stabilization of the shoulder.
PMID- 27495044
TI - Maternal HIV status affects the infant hemoglobin level: A comparative cross
sectional study.
AB - Children, especially infants, are highly vulnerable to iron-deficiency anemia
because of their rapid growth of the brain and the rest of the body. The
objectives of this study were to compare the prevalence of iron-deficiency anemia
in infants born from HIV-positive mothers and HIV-negative mothers and to
identify the determinants of iron-deficiency anemia in infants.A comparative
cross-sectional study was conducted in Bahir Dar city. Simple random sampling
technique was used to select the study participants. Mothers were interviewed;
blood samples were collected from mothers and infants to measure the hemoglobin
level and anthropometric indicators were obtained from the infants using world
health organization standards. Descriptive statistics were used to estimate the
prevalence of infantile anemia. Binary logistic regression and multiple linear
regressions were used to identify the determinants of infant anemia.A total of
1459 infants born from HIV-positive and HIV-negative mothers were included. The
prevalence of iron-deficiency anemia in infants born from HIV-positive and HIV
negative mothers was 41.9% (95% CI: 39-44). Infantile iron-deficiency anemia was
associated with maternal HIV infection (adjusted odds ratio [AOR] 2.54 [95% CI:
1.65-3.9]), stunting (AOR 3.46 [95% CI: 2.41-4.97]), low income (AOR 2.72 [95%
CI: 2-3.73]), maternal malaria during pregnancy (AOR 1.81 [95% CI: 1.33-2.47]),
use of cow milk before 6 month (AOR 1.82 [95% CI: 1.35-2.45]), residence (AOR
0.09 [95% CI: 0.06-0.13]), history of cough or fever 7 days preceding the survey
(AOR 2.71 [95% CI: 1.99-3.69]), maternal hemoglobin (B 0.65 [95% CI: 0.61-0.68]),
educational status of mother (B 0.22 [95% CI: 0.2-0.23]), age of the mother (B
0.03 [95% CI: -0.03, -0.02]), and family size (B -0.14 [95% CI: -0.18,-0.11]).
PMID- 27495045
TI - Pancreatic panniculitis associated with pancreatic carcinoma: A case report.
AB - INTRODUCTION: Pancreatic panniculitis is a very rare complication of pancreatic
cancer, most often accompanying rare acinar cell carcinoma. We herein report a
case of pancreatic panniculitis that was associated with pancreatic mucinous
adenocarcinoma. PATIENT INFORMATION: A 57-year-old male was referred to our
hospital for weight loss. A physical examination revealed subcutaneous nodules on
his lower extremities. The blood test showed abnormal increases in amylase,
lipase, and carbohydrate antigen 19-9 levels. A computed tomography scan detected
a hypodense 2 * 1.5 cm solid mass with an unclear margin in the head of the
pancreas. The biopsy of subcutaneous nodules on the lower extremities was
conducted and revealed lobular panniculitis. Pancreatic cancer and pancreatic
panniculitis were strongly suspected. After the administration of octreotide
acetate and the Whipple procedure, the serous amylase and lipase levels returned
to normal, and the pancreatic panniculitis had almost resolved by 4 weeks later.
CONCLUSION: Pancreatic panniculitis is a rare complication of pancreatic cancer.
However, in the presence of a pancreatic mass, as in this case, clinicians should
be aware that panniculitis may be the sentinel of pancreatic carcinoma.
PMID- 27495046
TI - Risk factors for mortality in patients with Stenotrophomonas maltophilia
bacteremia.
AB - Stenotrophomonas maltophilia is a nosocomial pathogen associated with high
morbidity and mortality, particularly in immunocompromised or critically ill
patients. In this study, we investigated the risk factors for mortality in
patients with S. maltophilia bacteremia.Retrospectively, medical records from all
patients with S. maltophilia bacteremia between December 2005 and 2014 at
Severance Hospital, a 2000-bed tertiary care hospital in Seoul, Korea, were
reviewed. Analysis was performed to identify factors associated with 28-day
mortality.In total, 142 bacteremia patients were enrolled in this study. The
overall 28-day mortality rate was 36.6%. Based on the univariate analysis,
hematologic malignancy (P = 0.015), Sepsis-related Organ Failure Assessment
(SOFA) score (P < 0.001) and the removal of a central venous catheter (CVC) (P =
0.040) were significantly related to mortality. In the intensive care unit
patients, the Acute Physiology and Chronic Health Evaluation II score (P = 0.001)
also had significance. Based on the multivariate analysis, the SOFA score (odds
ratio [OR] = 1.323; 95% confidence interval [CI]: 1.159, 1.509; P < 0.001) and
removal of the CVC (OR = 0.330; 95% CI: 0.109, 0.996; P = 0.049) were independent
factors associated with mortality.Our results suggest that removing a CVC may
considerably reduce mortality in patients with S. maltophilia bacteremia.
PMID- 27495047
TI - The outcomes of patients with severe dengue admitted to intensive care units.
AB - Outcomes of adult patients with dengue infections requiring intensive care unit
(ICU) admissions remain unclear. We assessed the clinical manifestations and
prognostic factors of patients critically ill with severe dengue.This
retrospective study was done in a tertiary referral hospital with 96 adult ICU
beds. All of the patients with laboratory-confirmed severe dengue infections and
admitted to the ICU were enrolled between July 31 and November 31, 2015, during
the large outbreak period. The medical records of all the recruited patients were
reviewed for the following information: age, gender, clinical manifestations,
disease severity scores, underlying conditions, laboratory examinations, and
outcomes. The primary endpoint was to find the predictors of ICU mortality.During
the study period, 4787 patients with dengue infections required ICU admission.
One hundred forty-three (2.99%) were critically ill (mean age: 69.7 years).
Hypertension (n = 90, 62.9%) and diabetes mellitus (n = 70, 49.0%) were the 2
most common underlying diseases. Eighty critically ill patients (55.9%) had
cobacterial infections, and 33 had cobacteremia. The hematologic system failed
most often, followed by thoracic and cardiovascular systems. Fever was the most
common presentation (n = 112; 78.3%), followed by anorexia (n = 47; 32.9%) and
abdominal pain (n = 46; 32.2%). Overall, 33 patients died (mortality rate:
23.1%). Multivariate analysis showed that ICU mortality was significantly
associated with lower Glasgow Coma Scale (GCS) scores, lower platelet counts
before ICU discharge, and more organ failures.The number of severe dengue
patients who require ICU admission remains high. The mortality rate was
associated with lower GCS scores, lower platelet counts, and more organ failures.
In addition, more than half of the critically ill dengue patients had comorbid
bacterial infections.
PMID- 27495048
TI - A meta-analysis for efficacy and safety evaluation of transcatheter left atrial
appendage occlusion in patients with nonvalvular atrial fibrillation.
AB - OBJECTIVES: This meta-analysis was conducted to evaluate the efficacy and safety
of transcatheter left atrial appendage (LAA) occlusion in patients with
nonvalvular atrial fibrillation. METHODS: The randomized controlled trials (RCT)
or observational studies with any transcatheter LAA occlusion devices were
searched in PubMed, Embase, and Cochrane library from inception to November 2015.
The incidence rates from individual studies were combined to evaluate the
procedural efficacy and safety, including all-cause death, cardiac/neurological
death, stroke, transient ischemic attack (TIA), thrombosis, hemorrhagic
complications, and pericardial effusion/tamponade. RESULTS: Thirty-eight studies
involving 3585 patients and 6 different occlusion devices were eligible for our
inclusion criteria. The procedural failure rate for LAA closure was 0.02 (95% CI:
0.02-0.03). The all-cause mortality was 0.03 (95% CI: 0.02-0.03) and
cardiac/neurological mortality was 0 (95% CI: 0.00-0.01). The stroke/TIA rate was
estimated only 0.01 (95% CI: 0.01-0.01). The incidence of thrombus on devices was
0.01 (95% CI: 0.01-0.02). The major hemorrhagic complication rate was estimated
0.01 (95% CI: 0.00-0.01). Pericardial effusion/tamponade was estimated 0.02 (95%
CI: 0.02-0.03). No heterogeneity was observed for above pooled estimates (I = 0).
In devices subgroups analysis, the all-cause mortality and cardiac/neurological
mortality of PLAATO group were the highest (P = 0.01 and P < 0.01 respectively),
whereas the incidence of thrombus on devices in the ACP group was the highest (P
< 0.01). In follow-up period subgroups analysis, there were significant
differences in all-cause death, stroke/TIA, major hemorrhage, and pericardial
effusion/tamponade events between the shorter and longer follow-up period
subgroups (P < 0.05). However, the differences among the subgroups were
numerically small. CONCLUSIONS: the pooled data demonstrated that transcatheter
LAA occlusion was effective and safe in the patients with nonvalvular atrial
fibrillation who were not suitable for lifelong antithrombotic therapy.
PMID- 27495050
TI - Early diagnosis and follow-up of chronic active Epstein-Barr-virus-associated
cardiovascular complications with cardiovascular magnetic resonance imaging: A
case report.
AB - INTRODUCTION: Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is
characterized as chronic or recurrent mononucleosis-like symptoms and elevated
EBV deoxyribonucleic acid (EBV-DNA) copies. Cardiovascular complications have
high morbidity and mortality. The treatment regimen for CAEBV has not been
established yet, resulting in poor prognoses. Herein, we present a case of
cardiovascular magnetic resonance imaging (CMRI) evaluation with a series of
sequences for CAEBV-associated cardiovascular involvement, which has never been
reported. CASE PRESENTATION: A 16-year-old female (body weight, 55 kg) developed
a persistent fever and a positive EBV-DNA level of 28,000 copies/mL. Computed
tomography angiography (CTA) showed aneurysms involving the aorta and its major
branches, as well as multiple aneurysms and stenoses of the coronary arteries.
CMRI of the coronary arteries depicted the dilution and stenosis of the arterial
lumen as well as the thickening of the arterial wall. Late gadolinium enhancement
(LGE) showed subendocardial and transmural delayed enhancement of the left
ventricle, suggesting myocardial infarction.CAEBV and associated cardiovascular
complications were diagnosed. After treatment with Medrol and Leflunomide, the
clinical manifestation and serological parameters reversed to normal. However,
the EBV-DNA level increased again to 13,900 copies/mL 2 months later. A follow-up
with aorta CTA showed that the arterial walls of the bilateral common iliac
artery aneurysms were thicker with new-onset mural thrombi. The aorta CTA also
showed new-onset occlusion of the right coronary artery, but a follow-up of CMRI
at the same day did not find new-onset delayed enhancement lesion. CONCLUSION:
This case reminds clinicians of the vital importance of early diagnosis and close
follow-up of CAEBV-associated cardiovascular complications. With cine imaging,
coronary artery imaging, LGE imaging, and other novel techniques, CMRI can
effectively and comprehensively reveal the early and dynamic changes, and act as
an important tool in the field of cardiovascular diseases.
PMID- 27495049
TI - Conditional disease-free survival after liver transplantation for hepatocellular
carcinoma: A two-center experience.
AB - Traditionally, survival estimates following liver transplantation (LT) of
hepatocellular carcinoma (HCC) patients were calculated as survival from the
surgery date, but future survival probabilities can change over time and
conditional disease-free survival (CDFS) may provide patients and clinicians with
more accurate prognostic information. This study aimed to assess CDFS in HCC
patients after LT.Three hundred eighty-four HCC patients who underwent LT were
included. Disease-free survival (DFS) was calculated using the Kaplan-Meier
analysis. The 3-year CDFS, which represents the probability of remaining disease
free for an additional 3 years, was calculated.1-, 3-, and 5-year DFS rates after
LT were 69.9%, 45.8%, and 39.0 %, respectively. Based on the concept of CDFS, the
probability of surviving an additional 3 years given that the patient was disease
free at 1 year, 3 years, and 5 years were 58.4%, 76.9%, and 83.1%, respectively.
Multivariate analysis indicated that larger tumor size (hazard ratio [HR], 1.509;
95% CI, 1.146-1.985; P = 0.003) was associated with poorer DFS. Patients with
worse prognostic features at baseline demonstrated the greater increase in CDFS
over time.Survival estimates following liver transplantation of HCC patients
change according to survival time accrued since surgery. CDFS estimates improved
dramatically over time especially among patients with worse prognostic features
at the time of surgery. CDFS may be a useful tool in counseling patients with
HCC, as it is a more accurate assessment of future survival for those patients
who have already survived a certain amount of time.
PMID- 27495051
TI - Is poststroke complex regional pain syndrome the combination of shoulder pain and
soft tissue injury of the wrist?: A prospective observational study: STROBE of
ultrasonographic findings in complex regional pain syndrome.
AB - Patients with poststroke complex regional pain syndrome (CRPS) show different
symptoms compared to other types of CRPS, as they usually complain of shoulder
and wrist pain with the elbow relatively spared. It is thus also known by the
term "shoulder-hand syndrome."The aim of this study is to present a possible
pathophysiology of poststroke CRPS through ultrasonographic observation of the
affected wrist before and after steroid injection at the extensor digitorum
communis (EDC) tendon in patients suspected with poststroke CRPS.Prospective
evaluation and observation, the STROBE guideline checklist was used.Twenty-three
patients diagnosed as poststroke CRPS in accordance to clinical criteria were
enrolled. They had a Three Phase Bone Scan (TPBS) done and the cross-sectional
area (CSA) of EDC tendon was measured by using ultrasonography. They were then
injected with steroid at the EDC tendon. The CSA of EDC tendon, visual analogue
scale (VAS), and degree of swelling of the wrist were followed up 1 week after
the injection.TPBS was interpreted as normal for 4 patients, suspected CRPS for
10 patients, and CRPS for 9 patients. Ultrasonographic findings of the affected
wrist included swelling of the EDC tendon. After the injection of steroid to the
wrist, CSA and swelling of the affected wrist compared to that before the
treatment was significantly decreased (P < 0.001). The VAS score declined
significantly after the injection (P < 0.001).Our results suggest that the
pathophysiology of poststroke CRPS might be the combination of frozen shoulder or
rotator cuff tear of shoulder and soft tissue injury of the wrist caused by the
hemiplegic nature of patients with stroke.
PMID- 27495052
TI - Monotypic plasma cell interstitial nephritis as the only clinical manifestation
in a patient with previously undiagnosed indolent multiple myeloma: A case
report.
AB - INTRODUCTION: Predominantly monotypic plasma cell infiltrates are an uncommon
renal finding in patients with malignant lymphoplasmacytic proliferation. CASE
PRESENTATION: We report the case of a 52-year-old man with chronic kidney disease
and significant proteinuria associated with a monoclonal immunoglobulin spike
(IgGkappa). Kidney biopsy revealed the presence of atypical multinucleated CD138
plasma cells with voluminous nuclei stained exclusively with a kappa antibody.
Electron microscopy showed mesangial and segmental parietal electron-dense,
nonorganized hyaline deposits without immunogold labeling for the kappa light
chain. The bone marrow aspirate revealed 6% of apparently mature plasmocytes
without dystrophy. We therefore concluded that the patient had an indolent
multiple myeloma with specific renal involvement in the form of malignant
monotypic interstitial plasmacytic infiltration. We initiated a specific
chemotherapy regimen including bortezomib-cyclophosphamide-dexamethasone. After 4
months of follow-up, creatinine levels had improved slightly and free kappa light
chain levels had decreased significantly within the normal range. CONCLUSION:
This case highlights the need to consider neoplastic interstitial plasma cell
infiltration systematically in patients diagnosed with an apparently benign
monoclonal gammopathy and to consider adaptation of the chemotherapy regimen, to
improve renal function.
PMID- 27495053
TI - The interplay between hospital and surgeon factors and the use of sentinel lymph
node biopsy for breast cancer.
AB - BACKGROUND: Several surgeon characteristics are associated with the use of
sentinel lymph node biopsy (SLNB) for breast cancer. No studies have
systematically examined the relative contribution of both surgeon and hospital
factors on receipt of SLNB. OBJECTIVE: To evaluate the relationship between
surgeon and hospital characteristics, including a novel claims-based
classification of hospital commitment to cancer care (HC), and receipt of SLNB
for breast cancer, a marker of quality care. DATA SOURCES/STUDY DESIGN:
Observational prospective survey study was performed in a population-based cohort
of Medicare beneficiaries who underwent incident invasive breast cancer surgery,
linked to Medicare claims, state tumor registries, American Hospital Association
Annual Survey Database, and American Medical Association Physician Masterfile.
Multiple logistic regression models determined surgeon and hospital
characteristics that were predictors of SLNB. RESULTS: Of the 1703 women treated
at 471 different hospitals by 947 different surgeons, 65% underwent an initial
SLNB. Eleven percent of hospitals were high-volume and 58% had a high commitment
to cancer care. In separate adjusted models, both high HC (odds ratio [OR] 1.53,
95% confidence interval [CI] 1.12-2.10) and high hospital volume (HV, OR 1.90,
95% CI 1.28-2.79) were associated with SLNB. Adding surgeon factors to a model
including both HV and HC minimally modified the effect of high HC (OR 1.34, 95%
CI 0.95-1.88) but significantly weakened the effect of high HV (OR 1.25, 95% CI
0.82-1.90). Surgeon characteristics (higher volume and percentage of breast
cancer cases) remained strong independent predictors of SLNB, even when
controlling for various hospital characteristics. CONCLUSIONS: Hospital factors
are associated with receipt of SLNB but surgeon factors have a stronger
association. Since regionalization of breast cancer care in the U.S. is unlikely
to occur, efforts to improve the surgical care and outcomes of breast cancer
patients must focus on optimizing patient access to SLNB by ensuring hospitals
have the necessary resources and training to perform SLNB, staffing hospitals
with surgeons who specialize/focus in breast cancer and referring patients who do
not have access to SLNB to an experienced center.
PMID- 27495054
TI - Role of gender in types and frequency of coronary artery aneurysm and ectasia.
AB - This study aimed to evaluate the role of gender in types and frequency of
coronary artery aneurysm and ectasia.We assessed retrospectively the angiography
records of 6100 patients. At first, we mainly reviewed angiographic movies for
the presence of coronary ectasia and/or aneurysm. Consequently, based on the
number of the coronary artery involvement, the coronary ectasia and aneurysm were
graded as mild if 1 coronary artery was involved and severe if 2 or more coronary
arteries were involved. The location of ectasia and aneurysm was analyzed with
respect to their isolated or combined location on various coronary arteries. The
patients included in the present study were divided into 2 groups based on their
gender as male and female. Then, we evaluated the impact of gender on severity
and the location of the ectasia and aneurysm.The incidence of the aneurysm and
ectasia was 3.5%. Among the patients with aneurysm and ectasia, 6.9% were male
and 4.5% were female. Aneurysm and ectasia were evaluated together; their
frequency was significantly higher in the male than female patients (P < 0.01).
However, when their incidence was evaluated separately, coronary artery ectasia
was markedly greater in male patients with regard to female patients (P < 0.01).
Incidence of CAE presence on the RCA was significantly greater in males than
females (2.7% vs 1.9%, P < 0.05).This study showed that incidence of CAE is more
common in males than females. Particularly, frequency for the involvement of CAE
on RCA and concurrently on 3 vessels is greater in male patients than female
patients.
PMID- 27495055
TI - Delay in cutaneous melanoma diagnosis: Sequence analyses from suspicion to
diagnosis in 211 patients.
AB - Advanced melanoma is an incurable disease with complex and expensive treatments.
The best approach to prevent melanoma at advanced stages is an early diagnosis. A
knowledge of factors associated with the process of detecting cutaneous melanomas
and the reasons for delays in diagnosis is essential for the improvement of the
secondary prevention of the disease.Identify sociodemographic, individual, and
medical aspects related to cutaneous melanoma diagnosis delay.Interviews
evaluated the knowledge of melanoma, signals, symptoms, persons who were
suspected, delays in seeking medical attention, physician's deferrals, and
related factors of 211 patients.Melanomas were self-discovered in 41.7% of the
patients; healthcare providers detected 29.9% of patients and others detected
27%. The main component in delay was patient-related. Only 31.3% of the patients
knew that melanoma was a serious skin cancer, and most thought that the pigmented
lesion was not important, causing a delay in seeking medical assistance. Patients
(36.4%) reported a wait interval of more than 6 months from the onset of an
observed change in a pigmented lesion to the first visit to a physician. The
delay interval from the first physician visit to a histopathological diagnosis
was shorter (<1 month) in 55.5% of patients. Improper treatments without a
histopathological confirmation occurred in 14.7% of patients. A professional
delay was related to both inappropriate treatments performed without
histopathological confirmation (P = 0.003) and long requirements for medical
referrals (P < 0.001).A deficient knowledge in the population regarding melanoma
and physicians' misdiagnoses regarding suspicious lesions contributed to delays
in diagnosis.
PMID- 27495056
TI - Salt intake belief, knowledge, and behavior: a cross-sectional study of older
rural Chinese adults.
AB - Excess sodium consumption is a major cause of high blood pressure and subsequent
vascular disease. However, the factors driving people's salt intake behavior
remains largely unknown. This study aims to assess the relationship of salt
intake behaviors with knowledge and belief on salt and health among older adults
in rural China.A cross-sectional survey was conducted among 4693 older
participants (men >=50 and women >=60 years old) randomly selected from 120 rural
villages in 5 northern provinces in China. Healthy salt intake behavior was
defined as either not eating pickled foods or not adding pickles/soy sauce/salt
when food was not salty enough in prior 3 months.There were 81% participants
having healthy salt intake behavior. Healthy salt intake behavior was more common
among women (P < 0.01) and was positively associated with age (P < 0.01) and
poorer health status (P < 0.01), but negatively associated with years in school
(P < 0.05). After adjusting for age, sex, years in school, and health status,
participants who believed in the harm of high salt intake were more likely to
have healthy salt intake behavior, compared with those who did not believe (Odds
Ratio = 1.6, P < 0.001). Knowledge of salt intake was not significantly related
to healthy salt intake behavior.Our study demonstrated that belief in the harm of
high salt intake rather than knowledge about salt and health was associated with
healthy salt intake behavior, independent of age, sex, years in school, and
health status. Future population salt reduction programs should place more
emphasis on establishing health beliefs rather than only delivering salt-related
knowledge.Clinical trial registration number of the study is NCT01259700.
PMID- 27495057
TI - Hospital mortality of patients aged 80 and older after surgical repair for type A
acute aortic dissection in Japan.
AB - To evaluate whether patients aged 80 and older have higher risk of hospital
mortality after repair of type A acute aortic dissection (TAAAD).Emergency
surgery for TAAAD in patients aged 80 and older remains a controversial issue
because of its high surgical risk.Data from patients who underwent surgical
repair of TAAAD between April 2011 and March 2013 were retrospectively extracted
from the Japanese Diagnosis Procedure Combination database. The effect of age on
hospital mortality was evaluated using multivariate logistic regression
analysis.A total of 5175 patients were enrolled. The mean age of patients was
67.1 +/- 13.0 years, and the male:female ratio was 51:49. Patients aged 80 and
older more frequently received tracheostomy than their younger counterparts (9.5%
vs 5.4%, P <0.001). Intensive care unit and hospital stays were significantly
longer in the elderly cohort versus the younger cohort (7.6 vs 6.7 days, P
<0.001, and 42.2 vs 35.8 days, P <0.001, respectively). Logistic regression
analysis showed that age >=80 years was significantly associated with a higher
risk of hospital mortality (adjusted odds ratio, 1.62; 95% confidence interval,
1.28-2.06; P <0.001). In linear regression analysis, age >=80 years was also
significantly associated with longer hospital stay (P = 0.007).In a large,
nationwide, Japanese database, patients aged 80 and older were at increased risk
of hospital mortality and length of hospital stay.
PMID- 27495058
TI - Abnormal increase of intraocular pressure in fellow eye after severe ocular
trauma: A case report.
AB - BACKGROUND: An ocular injury can lead to secondary glaucoma in the traumatized
eye in 3% to 20% of cases. Literature on the risk of developing elevated
intraocular pressure in the nontraumatized fellow eye is scant. Clinicians
treating ocular traumas should also bear in mind sympathetic ophthalmia, a rare
bilateral granulomatous panuveitis following accidental or surgical trauma to 1
eye. CASE REPORT: We report a case of high-pressure glaucoma of the fellow eye
without any signs of uveitis. The left eye of a 24-year-old man was injured in an
inadvertent movement during a free-time table-tennis match. The eye was severely
crushed, leading to blindness. His right eye developed medically uncontrolled
high-pressure glaucoma only 1 month after the injury. CONCLUSION: To the best of
our knowledge, there are no previous reports of post-traumatic glaucoma in the
nontraumatized eye after open-globe injury.
PMID- 27495059
TI - Molecular evolution and the global reemergence of enterovirus D68 by genome-wide
analysis.
AB - Human enterovirus D68 (EV-D68) was first reported in the United States in 1962;
thereafter, a few cases were reported from 1970 to 2005, but 2 outbreaks occurred
in the Philippines (2008) and the United States (2014). However, little is known
regarding the molecular evolution of this globally reemerging virus due to a lack
of whole-genome sequences and analyses. Here, all publically available sequences
including 147 full and 1248 partial genomes from GenBank were collected and
compared at the clade and subclade level; 11 whole genomes isolated in Taiwan
(TW) in 2014 were also added to the database. Phylogenetic trees were constructed
to identify a new subclade, B3, and represent clade circulations among strains.
Nucleotide sequence identities of the VP1 gene were 94% to 95% based on a
comparison of subclade B3 to B1 and B2 and 87% to 91% when comparing A, C, and D.
The patterns of clade circulation need to be clarified to improve global
monitoring of EV-D68, even though this virus showed lower diversity among clades
compared with the common enterovirus EV-71. Notably, severe cases isolated from
Taiwan and China in 2014 were found in subclade B3. One severe case from Taiwan
occurred in a female patient with underlying angioimmunoblastic T-cell lymphoma,
from whom a bronchoalveolar lavage specimen was obtained. Although host factors
play a key role in disease severity, we cannot exclude the possibility that EV
D68 may trigger clinical symptoms or death. To further investigate the genetic
diversity of EV-D68, we reported 34 amino acid (aa) polymorphisms identified by
comparing subclade B3 to B1 and B2. Clade D strains had a 1-aa deletion and a 2
aa insertion in the VP1 gene, and 1 of our TW/2014 strains had a shorter deletion
in the 5' untranslated region than a previously reported deletion. In summary, a
new subclade, genetic indels, and polymorphisms in global strains were discovered
elucidating evolutionary and epidemiological trends of EV-D68, and 11 genomes
were added to the database. Virus variants may contribute to disease severity and
clinical manifestations, and further studies are needed to investigate the
associations between genetic diversity and clinical outcomes.
PMID- 27495060
TI - rs1495741 as a tag single nucleotide polymorphism of N-acetyltransferase 2
acetylator phenotype associates bladder cancer risk and interacts with smoking: A
systematic review and meta-analysis.
AB - Rs1495741 has been identified to infer N-acetyltransferase 2 (NAT2) acetylator
phenotype, and to decrease the risk of bladder cancer. However, a number of
studies conducted in various regions showed controversial results. To quantify
the association between rs1495741 and the risk of bladder cancer and to estimate
the interaction effect of this genetic variant with smoking, we performed a
systematic literature review and meta-analysis involving 14,815 cases and 58,282
controls from 29 studies. Our results indicates rs1495741 significantly
associated with bladder cancer risk (OR = 0.85, 95% CI = 0.82-0.89, test for
heterogeneity P = 0.36, I = 7.0%). And we verified this association in
populations from Europe, America, and Asia. Further, our stratified meta-analysis
showed rs1495741's role is typically evident only in ever smokers, which suggests
its interaction with smoking. This study may provide new insight into gene
environment study on bladder cancer.
PMID- 27495061
TI - Association of depression and psychotropic medication on cardiac-related outcomes
in a nationwide community-dwelling elderly population in Taiwan.
AB - The objective of this study was to examine the association of depression,
psychotropic medications, and mental illness with cardiovascular disease in a
nationwide community-dwelling elderly population in Taiwan. A total of 5664
participants who enrolled in the Healthy Aging Longitudinal Study in Taiwan
(HALST) were included in the study. Multiple logistic regression was applied to
investigate the association of depression, psychotropic medication use, and
mental illness, separately, with cardiovascular disease. The results suggested
that cardiovascular disease was significantly associated with various definitions
of depression, including: the Center for Epidemiologic Studies-Depression scale
(CES-D) >= 16, self-reported, and physician-diagnosed for depression (adjusted
odds ratio [AOR] = 1.51; 95% confidence interval (CI): 1.14-2.00 for CES-D; AOR =
3.29; 95% CI: 1.99-5.42 for self-reported; and AOR = 2.45; 95% CI: 1.51-3.97 for
physician-diagnosed). Additionally, significant associations of cardiovascular
disease with the use of antipsychotics (AOR = 2.04; 95% CI: 1.25-3.34),
benzodiazepines (BZDs) (AOR = 1.84; 95% CI: 1.52-2.21), and Z-drugs (AOR = 1.41;
95% CI: 1.03-1.93), respectively, were also observed, but not the use of
antidepressants. In addition, a significant association of cardiovascular disease
with mental illness was found in this study (AOR = 2.33; 95% CI: 1.68-3.24). In
line with previous reports, these findings provided supportive evidence that
depression and/or mental illness were significantly associated with
cardiovascular disease in a community-dwelling elderly population in Taiwan.
Moreover, significant associations of cardiovascular disease with the use of
antipsychotics, BZDs, and Z-drugs, individually, were found. Further
investigation would be of importance to clarify the causal relationship of
depression and/or psychotropic medications with cardiovascular disease,
especially among elderly populations.
PMID- 27495062
TI - Impact on long-term survival of the number of lymph nodes resected in patients
with pT1N0 gastric cancer after R0 resection: A multicenter study in China.
AB - Although studies on the association between the number of lymph nodes resected
and prognosis in patients with pT2-4N0 stages of gastric cancer have reported
consistent results, there is no consensus on the optimal number of lymph nodes to
be examined for pT1N0 stage gastric cancer. The aim of this study was to evaluate
the long-term effect of the number of lymph nodes removed on the outcomes of
patients with pT1N0 stage gastric cancer after R0 resection.From December 2009 to
December 2011, 227 patients undergoing R0 resection of pT1N0 stage gastric cancer
at 4 Chinese centers were enrolled in this study. Patients were assigned to 2
groups according to the number of lymph nodes dissected (<=15 or > 15). Standard
survival methods and restricted multivariable Cox regression models were
applied.More women (P = 0.031) were in the <=15 group than in the >15 group. The
mean number of lymph nodes removed from women was greater than that from men (P =
0.007). The 5-year survival rate was significantly higher in the >15 lymph nodes
resected group than the <=15 group. The number of lymph nodes resected was
identified as an independent prognostic factor and was significantly correlated
with overall survival (OS).A lymphadenectomy with dissection of more than 15
lymph nodes improved the long-term survival of patients with pT1N0 gastric cancer
after R0 resection. Therefore, it is necessary to consider removing more than 15
lymph nodes among such patients.
PMID- 27495063
TI - Effectiveness of low-level laser on carpal tunnel syndrome: A meta-analysis of
previously reported randomized trials.
AB - BACKGROUND: Low-level laser therapy (LLLT) has been applied in the treatment of
carpal tunnel syndrome (CTS) for an extended period of time without definitive
consensus on its effectiveness. This meta-analysis was conducted to evaluate the
effectiveness of low-level laser in the treatment of mild to moderate CTS using a
Cochrane systematic review. METHODS: We conducted electronic searches of PubMed
(1966-2015.10), Medline (1966-2015.10), Embase (1980-2015.10), and ScienceDirect
(1985-2015.10), using the terms "carpal tunnel syndrome" and "laser" according to
the Cochrane Collaboration guidelines. Relevant journals or conference
proceedings were searched manually to identify studies that might have been
missed in the database search. Only randomized clinical trials were included, and
the quality assessments were performed according to the Cochrane systematic
review method. The data extraction and analyses from the included studies were
conducted independently by 2 reviewers. The results were expressed as the mean
difference (MD) with 95% confidence intervals (CI) for the continuous outcomes.
RESULTS: Seven randomized clinical trials met the inclusion criteria; there were
270 wrists in the laser group and 261 wrists in the control group. High
heterogeneity existed when the analysis was conducted. Hand grip (at 12 weeks)
was stronger in the LLLT group than in the control group (MD = 2.04; 95% CI: 0.08
3.99; P = 0.04; I = 62%), and there was better improvement in the visual analog
scale (VAS) (at 12 weeks) in the LLLT group (MD = 0.97; 95% CI: 0.84-1.11; P <
0.01; I = 0%). The sensory nerve action potential (SNAP) (at 12 weeks) was better
in the LLLT group (MD = 1.08; 95% CI: 0.44-1.73; P = 0.001; I = 0%). However, 1
included study was weighted at >95% in the calculation of these 3 parameters.
There were no statistically significant differences in the other parameters
between the 2 groups. CONCLUSION: This study revealed that low-level laser
improve hand grip, VAS, and SNAP after 3 months of follow-up for mild to moderate
CTS. More high-quality studies using the same laser intervention protocol are
needed to confirm the effects of low-level laser in the treatment of CTS.
PMID- 27495064
TI - Impact of surgical correction of tetralogy of fallot on short-term right and left
ventricular function as determined by 2-dimensional speckle tracking
echocardiography.
AB - Right ventricular (RV) and left ventricular (LV) dysfunction is an important
determinant of poor clinical status in repaired patients with tetralogy of Fallot
(TOF). The purpose of our study is to assess the impact of surgical repair on
short-term RV and LV function by 2-dimensional speckle tracking echocardiography
(STE).Sixty-seven patients (median age 12 months) with TOF before and 6 months
after repair and 35 healthy subjects were studied. The patients were divided into
the younger (age at surgery <=12 months) and older (age at surgery >12 months)
subgroups. RV and LV global longitudinal systolic strain and strain rate (SR),
and LV global circumferential and radial systolic strain and SR were measured by
STE. After repair, RV longitudinal strain and SR increased in the younger
patients, whereas RV longitudinal SR was decreased in the older patients. LV
deformation parameters were unchanged in all patients. In the multivariate
analysis, patients with better RV and LV deformation parameters preoperatively
were identified to have better RV and LV strain and SR postoperatively (P < 0.05
for all). The surgical approach of the pulmonary valve ring was predictive of RV
and LV systolic function postoperatively (P < 0.05 for all).After TOF repair,
short-term RV function improvement is identified in the younger but not in the
older patients, whereas LV function is unchanged in all patients. The
preoperative RV and LV deformational indices are the determinant of postoperative
biventricular function improvement. STE appears to be a valuable tool for
assessment of biventricular function after congenital heart disease surgery.
PMID- 27495065
TI - The association between biliary tract inflammation and risk of digestive system
cancers: A population-based cohort study.
AB - The relationship between biliary tract inflammation (BTI) and digestive system
cancers is unclear. This study aimed to evaluate the association between BTI and
the risks of digestive system cancers.Using the Taiwan National Health Insurance
claims data, information on a cohort of patients diagnosed with BTI (n = 4398)
between 2000 and 2009 was collected. A comparison cohort of sex-, age-, and index
year-matched persons without BTI (n = 17,592) was selected from the same
database. The disease was defined by the ICD-9-CM. Both cohorts were followed
until the end of 2010 and incidences of digestive system cancers were
calculated.The results revealed an increase in adjusted hazard ratio (aHR) of
biliary tract cancer (24.45; 95% confidence interval [CI]: 9.20-65.02), primary
liver cancer (1.53; 95% CI: 1.07-2.18), and pancreatic cancer (3.10; 95% CI: 1.20
8.03) in patients with both gallbladder and BTI. The aHR of stomach cancer was
also found to be increased (2.73; 95% CI: 1.28-5.81) in patients with gallbladder
inflammation only. There were no differences in esophageal cancer (aHR: 0.82; 95%
CI: 0.23-2.87) and colorectal cancer (aHR: 0.92; 95% CI: 0.59-1.45). The aHR for
digestive system cancers increased by 3.66 times (95% CI: 2.50-5.35) and 12.20
times (95% CI: 8.66-17.17) in BTI visits frequency averaged 2 to 4 visits per
year and frequency averaged >=5 visits per year, respectively.Patients with BTI
have significantly higher risk of digestive system cancers, particularly biliary
tract, pancreatic, and primary liver cancers, compared with those who are without
it.
PMID- 27495066
TI - A retrospective observational study of functional outcomes, length of stay, and
discharge disposition after an inpatient stroke rehabilitation program in Saudi
Arabia.
AB - Functional outcomes, length of stay (LOS), and discharge disposition have become
frequent outcome measures among stroke patients after rehabilitation programs. To
examine the trends of changes in functional outcomes, LOS, and discharge
disposition in stroke patients discharged from an inpatient rehabilitation
facility.All patients (n = 432) were admitted to a tertiary inpatient
rehabilitation hospital in Riyadh, Saudi Arabia with stroke diagnoses from
November 2008 to December 2014. The functional independence measure (FIM)
instrument used to assess the patient's functional status. The LOS was measured
as the number of days the patients spent in the hospital from the day of
admission to the day of discharge. The FIM efficiency was used to measure the
patient's rehabilitation progress. All of the variables of the prospectively
collected data were retrospectively analyzed.There were significant changes by
years in the total FIM ranging from 23 to 29 (P < 0.001) and subscores: FIM motor
ranging from 20 to 26 (P < 0.001); FIM cognitive ranging from 1.8 to 3 (P <
0.001). The mean LOS remained constant, from 52 days in 2011 to 40 days in 2013.
The FIM efficiency was stable between years and ranged from 0.52 to 0.72. The
rates of discharge (to home) were significantly unstable and ranged from 100% in
2010 and 2011 to 92% in 2013.Our results suggest that functional outcomes in
patients with stroke have improved after an inpatient stroke rehabilitation
program between 2008 and 2014 even with a constant LOS. Discharge disposition has
remained unstable over this period. To improve the efficiency of the stroke
rehabilitation program in Saudi Arabia, there is a need to decrease the LOS and
emphasize a comprehensive interdisciplinary approach.
PMID- 27495067
TI - Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients
with normal to minimally elevated ALT and no cirrhosis.
AB - For chronic hepatitis B (CHB), alanine aminotransferase (ALT) >=2 * upper limit
of normal (ULN) is often used as a major criteria to initiate treatment in
absence of cirrhosis, though patients with lower ALT may not be free from future
risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of
antiviral therapy on HCC incidence based on ALT levels.We performed a
retrospective study on 3665 patients consisting of United States and Taiwanese
REVEAL-HBV cohort who were consecutive, treatment-naive, noncirrhotic CHB
patients aged >=40 years. Patients were categorized by ALT cutoffs (>=2 * ULN vs
<2 * ULN) and subgrouped by treatment status. Kaplan-Meier and Cox proportional
hazards models were used to calculate cumulative incidence and hazard ratio (HR)
of HCC adjusting for REACH-B scores.A total of 202 patients developed HCC.
Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence
interval 0.10-0.58; P = 0.001. HCC incidence per 100,000 person-years was
significantly higher in untreated versus treated patients, even for those with
ALT < 2 * ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients
with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) >= 2000 IU/mL, the
number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10
for patients with ALT < 2 * ULN and >=2 * ULN, respectively.After adjustment by
REACH-B score, antiviral treatment significantly decreased HCC incidence even in
patients with ALT < 2 * ULN. NNT to prevent 1 incident HCC after 10 years of
therapy was low (14-15) in patients with mildly elevated HBV DNA >= 2000 IU/mL
regardless of ALT levels.
PMID- 27495068
TI - The long noncoding RNAs PVT1 and uc002mbe.2 in sera provide a new supplementary
method for hepatocellular carcinoma diagnosis.
AB - Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver
in adults worldwide. Several studies have demonstrated that long noncoding RNAs
(lncRNAs) are involved in the development of various types of cancer, including
HCC. These findings prompted us to examine the detectability of lncRNAs in blood
samples from patients with HCC. In this study, we explored the expression levels
of 31 cancer-related lncRNAs in sera from 71 HCC patients and 64 healthy
individuals by reverse transcription and quantitative polymerase chain reaction
(RT-qPCR). We found that 25 lncRNAs could be detected in the serum and that 7 had
significantly different expression levels. A 2-lncRNA signature (PVT1 and
uc002mbe.2) identified by stepwise regression showed potential as a diagnostic
marker for HCC. The area under the receiver operating characteristic (ROC) curve
was 0.764 (95% CI: 0.684-0.833). The sensitivity and specificity values of this
serum 2-lncRNA signature for distinguishing HCC patients from the healthy group
were 60.56% and 90.62%, respectively. The diagnostic ability of the combination
of the serum 2-lncRNA signature with alpha-fetoprotein (AFP) was much greater
than that of AFP alone. The expression levels of the 2 lncRNAs were associated
with clinical parameters including tumor size, Barcelona Clinic Liver Cancer
(BCLC) stage, and serum bilirubin.
PMID- 27495069
TI - Splenectomy and risk of renal and perinephric abscesses: A population-based
cohort study in Taiwan.
AB - Little epidemiological research is available on the relationship between
splenectomy and renal and perinephric abscesses. The purpose of the study was to
examine this issue in Taiwan.We conducted a population-based retrospective cohort
study using the hospitalization dataset of the Taiwan National Health Insurance
Program. A total of 16,426 participants aged 20 and older who were newly
diagnosed with splenectomy from 1998 to 2010 were assigned to the splenectomy
group, whereas 65,653 sex-matched, age-matched, and comorbidity-matched, randomly
selected participants without splenectomy were assigned to the nonsplenectomy
group. The incidence of renal and perinephric abscesses at the end of 2011 was
measured in both groups. The multivariable Cox proportional hazards regression
model was used to measure the hazard ratio (HR) and 95% confidence interval (CI)
for risk of renal and perinephric abscesses associated with splenectomy and other
comorbidities including cystic kidney disease, diabetes mellitus, urinary tract
infection, and urolithiasis.The overall incidence rate of renal and perinephric
abscesses was 2.14-fold greater in the splenectomy group than that in the
nonsplenectomy group (2.24 per 10,000 person-years vs 1.05 per 10,000 person
years, 95% CI 2.02, 2.28). After controlling for sex, age, cystic kidney disease,
diabetes mellitus, urinary tract infection, and urolithiasis, the multivariable
regression analysis demonstrated that the adjusted HR of renal and perinephric
abscesses was 2.24 for the splenectomy group (95 % CI 1.30, 3.88), when compared
with the nonsplenectomy group. In further analysis, the adjusted HR markedly
increased to 7.69 for those comorbid with splenectomy and diabetes mellitus (95%
CI 3.31, 17.9).Splenectomy is associated with renal and perinephric abscesses,
particularly comorbid with diabetes mellitus. In view of its potential morbidity
and mortality, clinicians should consider the possibility of renal and
perinephric abscesses when patients with splenectomy present with fever of
unknown origin.
PMID- 27495070
TI - The suitability of the GERDyzer instrument in pH-test-proven laryngopharyngeal
reflux patients.
AB - The use of validated patient-reported outcome (PRO) instruments for the treatment
outcome measure of laryngopharyngeal reflux (LPR) is crucial given the lack of
objective markers. However, current symptom-based PRO instruments can only
partially capture the impact of LPR. The GERD Analyzer (GERDyzer), an existing
disease-specific PRO instrument, which measures multidimensional health-related
quality of life (HRQL) affected by the illness rather than by any specific
symptoms, has been validated in patients with erosive gastroesophageal reflux
disease (GERD). Following the U.S. Food and Drug Administration PRO guidance, we
cross-culturally adapted the GERDyzer instrument into Chinese, and examined the
qualitative and quantitative psychometric properties of the Chinese version
GERDyzer in pH-test-proven LPR patients.The GERDyzer comprises 10 dimensions of
HRQL, including general well-being, pain/discomfort, physical health, diet,
energy, activities, leisure activities, social life, mood, and sleep. To examine
the content validity, we recruited 26 pH-test-proven LPR participants to conduct
4 focus group meetings for direct patient input on clinical manifestations and
HRQL impacts. We also tested the quantitative psychometric properties, including
reliability, validity, and responsiveness in 100 pH-test-proven LPR
patients.Saturation of concept elicitation was achieved from the 4 focus groups,
and a strong conceptual match was evident between the GERDyzer contents and
responses from the focus group participants. Cognitive debriefing assessment
showed that the Chinese version GERDyzer was adequate for use by patients as it
demonstrated linguistic validation and cultural harmonization. Quantitative
psychometric properties showed evidence of high internal consistency (Cronbach
alpha: 0.96), good to excellent test-retest reliability (intraclass correlation
coefficient: 0.84-0.98). Confirmatory factor analysis supported a 2-factor
structure. Convergent validity was confirmed by moderate correlation assessments
referencing the Reflux Symptoms Index and the Reflux Questionnaire. The
discriminant validity was supported by the ability to discriminate moderate-to
severe disease from mild disease. The responsiveness was also high in
participants with and without typical GERD symptoms (effect sizes 1.20 and 1.21,
respectively).In conclusion, the Chinese version GERDyzer instrument is a
reliable, valid, and responsive instrument for assessing HRQL in Taiwanese
patients with LPR.
PMID- 27495071
TI - Effects of cognitive behavioral coaching on depressive symptoms in a sample of
type 2 diabetic inpatients in Nigeria.
AB - BACKGROUND: Depression is one of the mental health problems confronting those
with diabetes mellitus and may result from self-defeating thoughts and
lifestyles. Therefore, the aim of this study was to investigate the effects of
cognitive behavioral coaching (CBC) program on depressive symptoms in a sample of
the Type 2 diabetic inpatients in Onitsha metropolis of Anambra State, Nigeria.
METHODS: The design of the study was pretest-post-test randomized control group
design. The participants were 80 Type 2 diabetic inpatients randomly assigned to
the treatment and control groups. The primary outcome measures were Beck's
Depression Inventory-II and a Diabetic Inpatient's Depressive Symptoms
Observation Checklist. Mean, standard deviation, repeated measures analysis of
covariance, and partial eta squared were used for data analysis. RESULTS: The
results revealed that the baseline of depressive symptoms was similar between the
control and treatment groups of the Type 2 diabetic inpatients. But, exposing the
Type 2 diabetic inpatients to a cognitive behavioral coaching program
significantly reduced the depressive symptoms in the treatment group compared to
those in the control group at the end of the intervention. The effects of
cognitive behavioral coaching program on the depressive symptoms of those in the
treatment group remained consistent at a 6 month follow-up meetings compared to
the control group. CONCLUSION: Given the potential benefits of a cognitive
behavioral coaching program, clinicians and mental health professionals are urged
to support and implement evidence-based cognitive-behavioral coaching
interventions aimed at promoting diabetic inpatients' wellbeing in the Nigerian
hospitals.
PMID- 27495072
TI - Pain related to robotic cholecystectomy with lower abdominal ports: effect of the
bilateral ultrasound-guided split injection technique of rectus sheath block in
female patients: A prospective randomised trial.
AB - BACKGROUND: Robotic cholecystectomy (RC) using port sites in the lower abdominal
area (T12-L1) rather than the upper abdomen has recently been introduced as an
alternative procedure for laparoscopic cholecystectomy. Therefore, we
investigated the time course of different components of pain and the analgesic
effect of the bilateral ultrasound-guided split injection technique for rectus
sheath block (sRSB) after RC in female patients. METHODS: We randomly assigned 40
patients to undergo ultrasound-guided sRSB (RSB group, n = 20) or to not undergo
any block (control group, n = 20). Pain was subdivided into 3 components:
superficial wound pain, deep abdominal pain, and referred shoulder pain, which
were evaluated with a numeric rating scale (from 0 to 10) at baseline (time of
awakening) and at 1, 6, 9, and 24 hours postoperatively. Consumption of fentanyl
and general satisfaction were also evaluated 1 hour (before discharge from the
postanesthesia care unit) and 24 hours postoperatively (end of study). RESULTS:
Superficial wound pain was predominant only at awakening, and after postoperative
1 hour in the control group. Bilateral ultrasound-guided sRSB significantly
decreased superficial pain after RC (P < 0.01) and resulted in a better
satisfaction score (P < 0.05) 1 hour after RC in the RSB group compared with the
control group. The cumulative postoperative consumption of fentanyl at 6, 9, and
24 hours was not significantly different between groups. CONCLUSIONS: After RC
with lower abdominal ports, superficial wound pain predominates over deep intra
abdominal pain and shoulder pain only at the time of awakening. Afterwards,
superficial and deep pain decreased to insignificant levels in 6 hours. Bilateral
ultrasound-guided sRSB was effective only during the first hour. This limited
benefit should be balanced against the time and risks entailed in performing RSB.
PMID- 27495073
TI - Fatty liver index as a simple predictor of incident diabetes from the KoGES
ARIRANG study.
AB - The fatty liver index (FLI), calculated from serum triglyceride, body mass index,
waist circumference, and gamma-glutamyltransferase, is considered a surrogate
marker of nonalcoholic fatty liver disease (NAFLD). We investigated whether FLI
predicts the development of diabetes mellitus (DM) and assessed the predictive
ability of FLI for new onset of DM in a prospective population-based cohort
study.We analyzed a total of 2784 adults (944 men and 1840 women) aged 40 to 70
years without DM at baseline. Participants were classified according to FLI
values into 3 groups: FLI < 30, no NAFLD; 30 <= FLI <= 59, intermediate NAFLD;
and FLI >= 60, participants with NAFLD. The area under the receiver-operating
characteristic curve (AUC), net reclassification improvement (NRI), and
integrated discrimination improvement (IDI) were calculated to determine whether
FLI improved DM risk prediction.During a mean of 2.6 years follow-up, 88 (3.16%)
participants developed DM. The odds ratio analyzed from multivariable-adjusted
models (95% confidence interval [CI]) for new onset of DM increased in a
continuous manner with increased FLI (<30 vs 30-59 vs >=60 = 1 vs 1.87 [95% CI
1.05-3.33] vs 2.84 [95% CI 1.4-5.75], respectively). The AUC significantly
increased when FLI was added to the conventional DM prediction model (0.835, 95%
CI: 0.789-0.881, P = 0.0289 vs traditional DM prediction model). The category
free NRI was 0.417 (95% CI: 0.199-0.635) and the IDI was 0.015 (95% CI: 0.003
0.026) for overall study participants.We found that FLI, a surrogate marker of
hepatic steatosis, resulted in significant improvement in DM risk prediction. Our
finding suggests that FLI may have clinical and prognostic information for
incident DM among the Korean adult population.
PMID- 27495074
TI - Effectiveness of fine-needle aspiration cytology in the diagnosis of lateral
cervical nonthyroid tumors.
AB - Given that the clinical and radiological examinations of lateral cervical masses
are not always sufficient for deciding on appropriate management, the cytological
examination of the material obtained by fine-needle aspiration might be an
efficient tool in the preoperative investigation of these lesions.In this
prospective cross-sectional study we evaluated the efficacy and diagnostic
accuracy of fine-needle aspiration cytology in the assessment of lateral cervical
nonthyroid tumors, by comparing its results with those of histopathology.A total
of 58 patients with lateral cervical masses were included. Preoperative
cytological results were compared with the histopathologic examination of
surgical specimens.Both cytology and histology indicated that malignant tumors
outnumbered benign lesions (62% vs 38%), with 88.9% of malignancies presenting in
patients aged >50 years, but cytology was less effective at differentiating
between benign and nontumor lesions. Cytology had 76.5% specificity and 78.1%
sensitivity for identifying malignant lateral cervical lesions, and there was a
concordance between the two diagnostic tests (McNemar test, P = 0.17, kappa =
0.50, P <0.001).Fine-needle aspiration cytology is a simple, quick, and effective
procedure that can aid in the preoperative evaluation of lateral cervical masses
by differentiating benign tumors and inflammatory processes from malignancies and
thus help in determining a subsequent therapeutic strategy.
PMID- 27495075
TI - Body mass index and the risk of incident functional disability in elderly
Japanese: The OHSAKI Cohort 2006 Study.
AB - The relationship between the body mass index (BMI) and the incidence of cause
specific disability remains unclear.We conducted a prospective cohort study of
12,376 Japanese individuals aged >=65 years who were followed up for 5.7 years.
Information on BMI and other lifestyle factors was collected via a questionnaire
in 2006. Functional disability data were retrieved from the public Long-term Care
Insurance database. BMI was divided into 6 groups (<21, 21-<23, 23-<25, 25
<27[reference], 27-<29 and >=29). Hazard ratios and 95% confidence intervals for
cause-specific disability were estimated using Cox proportional hazards
regression models.A U-shaped relationship between BMI and functional disability
was observed, with a nadir at 26. The nadir BMI values with the lowest disability
risk were 28 for dementia, 25 for stroke, and 23 for joint disease. A low BMI
(<23) was a risk factor for disability due to dementia, the HR values (95% CI)
being 2.48 (1.70-3.63) for BMI <21 and 2.25 (1.54-3.27) for BMI 21 to <23; a high
BMI (>=29) was a risk factor for disability due to joint disease, the HR value
(95% CI) being 2.17 (1.40-3.35). There was no significant relationship between
BMI and disability due to stroke.The BMI nadirs for cause-specific disability
differed: a low BMI (<23) was a risk factor for disability due to dementia, and a
high BMI (>=29) was a risk factor for disability due to joint disease. Because
BMI values of 23 to <29 did not pose a significantly higher risk for each cause
of disability, this range should be regarded as the optimal one for the elderly
population.
PMID- 27495076
TI - Seasonal changes of 24-hour intraocular pressure rhythm in healthy Shanghai
population.
AB - The aim of the present study was to investigate and compare the 24-hour
intraocular pressure (IOP) rhythms in winter and summer in the healthy population
of Shanghai, China.This is a cross-sectional study in which 24-hour IOP
measurements were taken for all eligible healthy volunteers in winter and summer,
respectively, and the temperature, hours of sunlight (sunlight time), and
circulatory parameters, including heart rate, systolic blood pressure, and
diastolic blood pressure, were also recorded. The 24-hour IOP curves and IOP
parameters (mean, peak, trough, and fluctuation of IOP together with the diurnal
to-nocturnal IOP change) in winter and summer were obtained and compared. The
magnitude of IOP changes from summer to winter was also calculated.A total of 29
participants (58 eyes), 14 (48.28%) male and 15 (51.72%) female, aged 43.66 +/-
12.20 (19-61) years, were considered eligible for this study. Generally, IOP
decreased progressively before noon, increased notably in the nocturnal period,
and peaked at 12:00 AM in winter and at 2:00 AM in summer. The pattern of 24-hour
IOP in winter and summer was significantly different (P = 0.002). The average
IOPs from 4:00 PM to 8:00 AM, except for 6:00 AM, were significantly higher in
winter (P < 0.05). However, no significant differences were shown after adjusting
for temperature and/or sunlight time. From summer to winter, the extent of IOP
increase was mostly around 0 to 3 mm Hg, and the IOPs increased more
significantly in the nocturnal period than in the diurnal period (P = 0.05).The
24-hour IOP rhythms were different in winter and summer, with higher IOP level in
winter. Temperature and sunlight time, which are independent of heart rate and
blood pressure, affected the 24-hour IOP rhythms in healthy people in Shanghai,
China. Further investigations are expected for the rhythm of some endogenous
substance secretion and the inner mechanism of regulation of IOP.
PMID- 27495077
TI - Long-term effects of pioglitazone on first attack of ischemic cerebrovascular
disease in older people with type 2 diabetes: A case-control study in Taiwan.
AB - Long-term studies demonstrating the effect of pioglitazone use on primary
prevention of ischemic cerebrovascular disease in older people with type 2
diabetes mellitus are lacking. This study investigated the relationship between
pioglitazone use and first attack of ischemic cerebrovascular disease in
Taiwan.We conducted a case-control study using the database of the Taiwan
National Health Insurance Program. There were 2359 type 2 diabetic subjects aged
>=65 years with newly diagnosed ischemic cerebrovascular disease from 2005 to
2011 as the case group and 4592 sex- and age-matched, randomly selected type 2
diabetic subjects aged >=65 years without ischemic cerebrovascular disease as the
control group. The odds ratio (OR) with 95% confidence interval (CI) of ischemic
cerebrovascular disease associated with pioglitazone use was measured by the
multivariable unconditional logistic regression model.After adjustment for
confounding factors, the multivariable logistic regression analysis disclosed
that the adjusted ORs of first attack of ischemic cerebrovascular disease
associated with cumulative duration of using pioglitazone were 3.34 for <1 year
(95% CI 2.59-4.31), 2.53 for 1 to 2 years (95% CI 1.56-4.10), 2.20 for 2 to 3
years (95% CI 1.05-4.64), and 1.09 for >=3 years (95% CI 0.55-2.15),
respectively.Our findings suggest that pioglitazone use does not have a
protective effect on primary prevention for ischemic cerebrovascular disease
among older people with type 2 diabetes mellitus during the first 3 years of use.
Whether using pioglitazone for >3 years would have primary prevention for
ischemic cerebrovascular disease needs a long-term research to prove.
PMID- 27495079
TI - Pseudoaneurysm of the aortic arch: A rare case report of pulmonary cancer
complication.
AB - BACKGROUND: Pseudoaneurysm of the aortic arch is uncommonly associated with
cancer, and is extremely rare in pulmonary cancer. Here, we report an unusual and
successfully treated case of aortic arch pseudoaneurysm in a male patient with
lung squamous cell carcinoma. METHODS: A 64-year-old male patient was admitted to
the Emergency Department, presenting with massive hemoptysis (>500 mL blood
during the 12 hours prior to treatment). The diagnosis of aortic arch
pseudoaneurysm was confirmed after inspection of computed tomographic angiography
and three-dimensional reconstruction. We processed the immediate endovascular
stent-grafting for this patient. RESULTS: This patient recovered with no filling
or enlargement of the pseudoaneurysm, no episodes of hemoptysis, and no
neurological complications during the 4-week follow-up period. CONCLUSION:
Herein, we compare our case with other cancer-related pseudoaneurysms in the
medical literature and summarize the clinical features and treatment of this
unusual case.
PMID- 27495078
TI - Comparison of image quality from filtered back projection, statistical iterative
reconstruction, and model-based iterative reconstruction algorithms in abdominal
computed tomography.
AB - The purpose of this study was to compare the image noise-reducing abilities of
iterative model reconstruction (IMR) with those of traditional filtered back
projection (FBP) and statistical iterative reconstruction (IR) in abdominal
computed tomography (CT) imagesThis institutional review board-approved
retrospective study enrolled 103 patients; informed consent was waived. Urinary
bladder (n = 83) and renal cysts (n = 44) were used as targets for evaluating
imaging quality. Raw data were retrospectively reconstructed using FBP,
statistical IR, and IMR. Objective image noise and signal-to-noise ratio (SNR)
were calculated and analyzed using one-way analysis of variance. Subjective image
quality was evaluated and analyzed using Wilcoxon signed-rank test with
Bonferroni correction.Objective analysis revealed a reduction in image noise for
statistical IR compared with that for FBP, with no significant differences in
SNR. In the urinary bladder group, IMR achieved up to 53.7% noise reduction,
demonstrating a superior performance to that of statistical IR. IMR also yielded
a significantly superior SNR to that of statistical IR. Similar results were
obtained in the cyst group. Subjective analysis revealed reduced image noise for
IMR, without inferior margin delineation or diagnostic confidence.IMR reduced
noise and increased SNR to greater degrees than did FBP and statistical IR.
Applying the IMR technique to abdominal CT imaging has potential for reducing the
radiation dose without sacrificing imaging quality.
PMID- 27495080
TI - Application of Kinesio Taping method for newborn swallowing difficultly: A case
report and literature review.
AB - BACKGROUND: Preterm infants are at an increased risk of sucking problems,
swallowing difficulty, and poor nourishment. During the neonatal period, the
neurobehavioral organization of a preterm baby is poor compared with that of
appropriate gestational age infants. Kinesio Taping has been widely used for
edema control, joint protection, and proprioception training. With the help of
augmentation of the sensory input for muscle facilitation and inhibition through
tapping, the coordination of the target muscle groups can be improved. Until now,
no research is available on the use of Kinesio Taping for the swallowing
difficulty of infant. METHODS: We reported a preterm infant suffering from brain
edema at birth and swallowing difficultly until 40 weeks. The swallowing reflex
was delayed. Moreover, lip closure and rooting reflex combined with the
dysfunction grade of jaw movement were poor. We performed KT methods on the baby
under the theory of the direction of the tape for facilitate or inhibit the
muscle. RESULT: After the Kinesio Taping treatment, the sucking function was
improved with good lip closure.One week later, the baby was discharged without
the use of an oral gastric tube. CONCLUSION: Kinesio Taping contributed
significantly to the improvement of impaired sucking and swallowing and could be
implemented as a regular rehabilitative approach for infants suffering from these
difficulties.
PMID- 27495081
TI - CT-guided percutaneous transthoracic needle biopsy for paramediastinal and
nonparamediastinal lung lesions: Diagnostic yield and complications in 1484
patients.
AB - Computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) is
used for identifying paramediastinal lung lesions that cannot be diagnosed by
bronchoscopy, but the diagnostic performance and complication rate are
unreported.This retrospective study was approved by the institutional review
board committee. A total of 1484 patients who underwent PTNB between April 2012
and April 2015 were enrolled. The cohort was divided into a paramediastinal (n =
195) and a nonparamediastinal group (n = 1289) based on lesion location.
Diagnostic yield for malignancy and complication rates were analyzed in both
groups. Univariate and multivariate logistic regression analysis was used to
determine independent risk factors for hemoptysis complication in the
paramediastinal group.Percutaneous transthoracic needle biopsy showed 95.6%
(109/114) sensitivity and 100% (77/77) specificity for the diagnosis of lesions
in the paramediastinal group, with similar accuracy (95.4%, 186/195) to that in
the nonparamediastinal group (94.7%, 1221/1289; P = 0.699). Compared with PTNB
for nonparamediastinal lesions, PTNB for paramediastinal lesions demonstrated a
comparable pneumothorax rate (8.21% vs 8.69%; P = 0.823) and hemothorax rate
(2.56% vs 1.47%; P = 0.261), and a higher hemoptysis rate (28.2% vs 19.4%; P =
0.005). Among 6 defined paramediastinal regions, the overall complication rate
was the highest in the posterior region (42.4%) and the lowest in the
paraventricular region (13.6%). Multivariate analysis revealed that lesion size
of 2 to 3 cm (odds ratio [OR] 3.22), intrapulmonary length of needle path >2 cm
(OR 8.85), and proximal to pulmonary artery (OR 10.33) were independent risk
factors for hemoptysis in the paramediastinal group.Computed tomography-guided
PTNB can diagnose paramediastinal lesions with high yield and acceptable
complication rates. Given higher rate of hemoptysis in PTNB for paramediastinal
lesions, more attention should be paid in cases with high risks.
PMID- 27495082
TI - Comparative assessment of therapeutic safety of norcantharidin, N-farnesyloxy
norcantharimide, and N-farnesyl-norcantharimide against Jurkat T cells relative
to human normal lymphoblast: A quantitative pilot study.
AB - The therapeutic safety of an anticancer drug is one of the most important
concerns of the physician treating the cancer patient. Half maximal inhibitory
concentration (IC50) and hillslope are usually used to represent the strength and
sensitivity of an anticancer drug on cancer cells. The therapeutic safety of the
anticancer drug can be assessed by comparing the IC50 and hillslope of anticancer
drugs on cancer cells relative to normal cells. Since there are situations where
"more anticancer activity" implies "more toxicity," the safety of an anticancer
drug in these situations is hard to evaluate by using IC50 and hillslope alone.
In a previous study, the "net effect" index was devised to represent the net
therapeutic effects of one anticancer drug relative to the other. However, the
therapeutic safety of one specific anticancer drug alone was not defined in the
"net effect" index. This study introduced the "safety index (SI)" to quantify the
degree of safety of an anticancer drug by using 4-parameter logistic model on
cancer cells relative to normal cells. The therapeutic safety of norcantharidin
(NCTD), N-farnesyloxy-norcantharimide (NOC15), and N-farnesyl-norcantharimide
(NC15) in the treatment of Jurkat T cells relative to human normal lymphoblast
was compared using the newly defined SI. We found that the SI of NOC15 and NC15
was significantly higher than that of NCTD, suggesting that both NOC15 and NC15
can damage more cancer cells and less normal cells than NCTD. We conclude that
both NOC15 and NC15 are safer anticancer drugs than NCTD in the treatment of
Jurkat T cells relative to human normal lymphoblast. The SI can be further
applied to the screening, developments, and applications of anticancer drugs in
the future.
PMID- 27495083
TI - Eight years of follow-up after laminectomy of calcium pyrophosphate crystal
deposition in the cervical yellow ligament of patient with Coffin-Lowry syndrome:
A case report.
AB - BACKGROUND: We report 8 years of follow-up after decompression to treat cervical
myelopathy in a patient with Coffin-Lowry syndrome (CLS). CLS is a rare X-linked
semidominant syndrome associated with growth and psychomotor retardation, general
hypotonia, and skeletal abnormalities. In this patient, the spinal cord was
compressed by calcium pyrophosphate crystal deposition in the cervical yellow
ligament (YL). To date, only 1 report has described clinical features after
surgery for calcified cervical YL in CLS. METHODS: A 15-year-old male with
tetraplegia secondary to compression of the cervical spinal cord induced by a
hypoplastic posterior arch of C1 and calcification of the YL from C2 to C7 was
treated surgically with laminectomy from C1 to C7. The patient's history,
clinical examination, imaging findings, and treatment are reported. The patient
was incapable of speech because of mental retardation, so he could not describe
his symptoms. Gait disturbance worsened over the 2 months before admission to our
hospital. At admission, the patient could not move his extremities, and tendon
reflexes of the upper and lower extremities were significantly increased.
Computed tomography of the cervical spine showed YL calcification from C2 to C7.
Magnetic resonance imaging showed consecutive compression of the cervical spinal
cord. We diagnosed quadriplegia secondary to cervical cord damage and performed
emergency surgery. RESULTS: During C1-C7 laminectomy, YL calcification in C2-C7
was observed. The calcification was confirmed as calcium pyrophosphate by crystal
analysis. Quadriplegia gradually resolved, and almost disappeared by 2 weeks
after the operation. Cervical hyperlordosis was observed in radiographs starting
from 1 month after the operation, but it has not progressed and is not associated
with any symptoms. CONCLUSIONS: The efficacy of decompression continued, and no
postoperative complications have occurred during at least 8 years of follow-up.
PMID- 27495084
TI - Aponeurosis of the levator palpebrae superioris in Chinese subjects: A live gross
anatomy and cadaveric histological study.
AB - An accurate understanding of the anatomy of the levator palpebrae superioris
aponeurosis (LPSA) is critical for successful blepharoplasty of aponeurotic
ptosis. We investigated the macroscopic and microscopic anatomy of the LPSA.This
prospective live gross anatomy study enrolled 200 adult Chinese patients with
bilateral mild ptosis undergoing elective blepharoplasty. Full-thick eyelid
tissues and sagittal sections from the eyelid skin to the conjunctiva were
examined with Masson trichrome staining or antismooth muscle actin (SMA)
immunohistochemistry.Gross anatomy showed that the space between the superficial
and deep layers of the LPSA could be accessed after incising the overlying
superficial fascia, by retracting the white line. Adipose layers were clearly
observed in 195 out of 200 patients with bilateral mild ptosis, among which 180
cases had the superficial layer connected to the uncoated adipose. Fifteen cases
had the superficial layer connected to the smoothly coated layer, and 5 cases had
the superficial layer directly connected to the deep loose fiber, almost without
adipose. In previously untreated patients, the LPSA space was located beneath the
intact orbital septum. In those with previous surgeries, it was beneath the
superficial layer of the LPSA, underlying the destructed orbital septum.
Cadaveric histology showed that the deep layer of the LPSA extended into the
anterior layer of the tarsal plate and the superficial layer reflexed upward in
continuity with the vertical orbital septum. An occult space existed between the
2 layers of the LPSA, with a smooth lining on the deep layer. The superficial
layer of the LPSA was SMA-immunonegative but the deep layer was slightly
immunopositive for SMA. An occult anatomic space exists between the superficial
and deep layers of the LPSA, in proximity to the superior tarsal plate margin.
Recognition of the more anatomically significant LPSA deep layer may help improve
the aesthetic outcome of blepharoplasty.
PMID- 27495085
TI - CONSORT: Effects of adding adefovirdipivoxil to peginterferon alfa-2a at
different time points on HBeAg-positivepatients: A prospective, randomized study.
AB - BACKGROUND: The aims of this study were to compare the efficacy and safety of the
addition of adefovir dipivoxil (ADV) (started at different time points) to
pegylated interferon alpha-2a (PEG-INF-alpha2a) and PEG-INF-alpha2a monotherapy.
This prospective, randomized study sought to evaluate the safety and efficacy of
the combination of PEG-INF-alpha2a and ADV at different time points.120 patients
were randomized into groups that received PEG-INF-alpha2a as monotherapy (group
A) or in combination with ADV started at week 0 (group B), 12 (group C), or 24
(group D). All patients were followed for 48 weeks. Efficacy and safety analyses
were performed. METHODS: Patients in group a received 135 MUg of PEG-INF-alpha2a
by subcutaneous injection once weekly for 48 weeks. Patients in the ADV add-on
group received 135 MUg of PEG-INF-alpha2a subcutaneously once weekly and received
10 mg of ADV administered once daily for 48 weeks. HBV DNA, HBsAg, HBeAg, and
hepatitis B e antibody levels were determined. Responses were determined at week
12 (ADV add-on), the end of treatment for PEG-INF-alpha2a (48weeks) and ADV (EOT)
and at the end of 96 weeks of follow-up (EOF). RESULTS: The rate of HBV DNA loss
were higher in the combination groups than group A at the week 12, week 48, the
EOT and EOF (P < 0.05). The rates of HBeAg seroconversion and HBsAg loss were
similar among the treatment groups (P>0.05). The alanineaminotransferase (ALT)
normalization rate was higher in the combination group than group A only at the
EOT (P = 0.007). By the EOF, the patients with ADV added at week 12 achieved
higher rates of HBV DNA loss (71.9%), HBeAg seroconversion (50.0%), HBsAg loss
(15.6%), and ALT normalization (78.1%). CONCLUSIONS: PEG-INF-alpha2a plus ADV
combination therapy is safe and superior to PEG-INF-alpha2amonotherapyfor
decreasing serum HBV DNA and normalizing the ALT level but has no significant
impact on the rate of HBeAg seroconversion and HBsAg loss. Adding ADV at week 12
may be an optimal combination strategy.
PMID- 27495086
TI - Genetic signatures of heroin addiction.
AB - Heroin addiction is a complex psychiatric disorder with a chronic course and a
high relapse rate, which results from the interaction between genetic and
environmental factors. Heroin addiction has a substantial heritability in its
etiology; hence, identification of individuals with a high genetic propensity to
heroin addiction may help prevent the occurrence and relapse of heroin addiction
and its complications. The study aimed to identify a small set of genetic
signatures that may reliably predict the individuals with a high genetic
propensity to heroin addiction. We first measured the transcript level of 13
genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1,
MBD1, and RGS3) in lymphoblastoid cell lines in a sample of 124 male heroin
addicts and 124 male control subjects using real-time quantitative PCR. Seven
genes (PRKCB, PDK1, JUN, CEBPG, CEBPB, ENO2, and HAT1) showed significant
differential expression between the 2 groups. Further analysis using 3
statistical methods including logistic regression analysis, support vector
machine learning analysis, and a computer software BIASLESS revealed that a set
of 4 genes (JUN, CEBPB, PRKCB, ENO2, or CEBPG) could predict the diagnosis of
heroin addiction with the accuracy rate around 85% in our dataset. Our findings
support the idea that it is possible to identify genetic signatures of heroin
addiction using a small set of expressed genes. However, the study can only be
considered as a proof-of-concept study. As the establishment of lymphoblastoid
cell line is a laborious and lengthy process, it would be more practical in
clinical settings to identify genetic signatures for heroin addiction directly
from peripheral blood cells in the future study.
PMID- 27495087
TI - Voriconazole treatment of Candida tropicalis meningitis: persistence of (1,3)
beta-D-glucan in the cerebrospinal fluid is a marker of clinical and
microbiological failure: A case report.
AB - INTRODUCTION: Infections are still the most common complications of cerebral
shunt procedures. Even though fungal etiologies are considered to be rare, they
are associated with significant morbidity and mortality. Due to their
uncommonness, diagnostic procedures and optimal therapy are poorly defined. We
report a case of Candida tropicalis infection of ventriculo-peritoneal
cerebrospinal fluid (CSF) shunt in a 49-year-old immune competent male treated
with voriconazole (VOR). METHODS: Microbiological and CSF markers (1,3-b-D-glucan
BDG) of fungal infection, biofilm production capacity, sensitivity of serial
isolates of the pathogen, and the concentration of the antifungal drug have been
monitored and related to the clinical course of this infection. RESULTS: Despite
appropriate treatment with VOR, in terms of adequate achieved CSF drug
concentrations and initial effective therapeutic response, loss of VOR
susceptibility of the C tropicalis and treatment failure were observed.
CONCLUSION: Biofilm production of the C. tropicalis isolate might have had a
significant role in treatment failure. Of interest, clinical and microbiological
unfavorable outcome was anticipated by persistence of BDG in CSF. Rising titers
of this marker were associated with relapse of fungal infection.
PMID- 27495088
TI - Complementary traditional Chinese medicine therapy improves survival in patients
with metastatic prostate cancer.
AB - More than 50% of prostate cancer patients have used traditional Chinese medicine
(TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate
cancer patients remains unclear. Here, we investigated the relationship between
TCM use and the survival of prostate cancer patients.A retrospective nationwide
cohort study of prostate cancer patients was conducted between 1998 and 2003
using the Taiwan National Health Insurance Research Database. Patients were
classified as TCM users or nonusers, and monitored from the day of prostate
cancer diagnosis to death or end of 2012. The association between death risk and
TCM use was determined using Cox proportional-hazards models and Kaplan-Meier
curves.Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%)
were TCM users and nonusers, respectively. The mean follow-up period was 8.38
years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality
rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with
longer TCM use, especially in patients who used TCM for ?200 days (adjusted
hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44-0.84). TCM users with
metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70,
95% CI 0.51-0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM
formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI
0.04-0.94).The result suggested that complementary TCM therapy might be
associated with a reduced risk of death in metastatic prostate cancer patients.
PMID- 27495089
TI - Hemophagocytic lymphohistiocytosis associated with SFTS virus infection: A case
report with literature review.
AB - BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a new emerging
zoonosis. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome
caused by hyperinflammation. Here, we report the case of SFTS-associated HLH.
CASE SUMMARY: A 62-year-old man was admitted to local hospital with 8 days of
fever and chill. He had leukopenia, thrombocytopenia, and developed seizure. An
attending physician examined bone marrow to rule out hematologic malignancy. He
was transferred to tertiary referral hospital for suspicious HLH. We decided to
confirm its histologic feature for sure. Bone marrow and liver biopsy showed
hemophagocyotic histiocytes. Serological tests for other infections were all
negative except SFTS virus polymerase chain reactions (PCRs) as positive from
serum, bone marrow, bronchoalveolar lavage fluid, and liver biopsy specimen. A
definitive diagnosis was SFTS-associated HLH. During 2 weeks of conservative
treatment, he succeeded in recovery from multiple organ failure. CONCLUSION: SFTS
should be considered one of differential diagnosis of HLH. In certain endemic
areas, SFTS infection deserves clinicians' attention because it can be presented
hematologic diseases as HLH.
PMID- 27495090
TI - Genetic polymorphisms in the CD14 gene are associated with monocyte activation
and carotid intima-media thickness in HIV-infected patients on antiretroviral
therapy.
AB - HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of
cardiovascular disease (CVD). Given the relationship between innate immune
activation and CVD, we investigated the association of single-nucleotide
polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT),
a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV
uninfected controls as a cross-sectional, case-control study. We quantified the
frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38,
HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma
levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by
ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for
CD14/-260SNP but not the CC/CT genotype was associated with elevated plasma
sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected
individuals. The TT genotype was associated with lower cIMT in HIV-infected
patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype
for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes
among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV
uninfected controls. SNPs in CD14/-260 and TLR4/+896 were significantly
associated with different markers of systemic and monocyte activation and cIMT
that differed between HIV-infected participants on ART and HIV-uninfected
controls. Further investigation on the relationship of these SNPs with a clinical
endpoint of CVD is warranted in HIV-infected patients on ART.
PMID- 27495091
TI - Method for discriminating synchronous multiple lung cancers of the same
histological type: miRNA expression analysis.
AB - With the development of imaging technology, an increasing number of synchronous
multiple lung cancers (SMLCs) have been diagnosed in recent years. Patients with
>1 tumor are diagnosed with either synchronous multiple primary lung cancers
(SMPLCs) or other primary tumors and metastases. Clinical guidelines,
histological characteristics, and molecular diagnostics have been used to
discriminate SMPLCs from other multiple lung cancers. However, there is still
ambiguity in the diagnosis of SMPLCs of the same histological type. We enrolled
24 patients with the same histological type of SMLCs and assessed their status
using established clinical guidelines, comprehensive histological subtyping, and
molecular analysis. The sum value of the differential microRNA (miRNA) expression
profiles (DeltaDeltaCt) with matched tumors was evaluated to discriminate SMPLCs
of the same histological type from metastases. Twelve patients with lymph node
metastases were included for comparison, and the sum value of the DeltaDeltaCt of
5 miRNAs between primary tumors and lymph node metastases was <9. Patients
definitively diagnosed with SMPLCs by integrated analysis were also classified as
SMPLCs by miRNA analysis; 6 patients showed conflicting diagnoses by integrated
and miRNA analysis and 14 were given the same classification. Analysis of miRNA
expression profiles is considered to be a useful tool for discriminating SMPLCs
from intrapulmonary metastases.
PMID- 27495092
TI - Nutritional status and physical inactivity in moderated asthmatics: A pilot
study.
AB - Preservation of nutritional status and of fat-free mass (FFM) and/or preventing
of fat mass (FM) accumulation have a positive impact on well-being and prognosis
in asthma patients. Physical inactivity is identified by World Health
Organization as the fourth leading risk factor for global mortality. Physical
activity (PA) may contribute to limit FM accumulation, but little information is
available on the interactions between habitual PA and body composition and their
association with disease severity in asthma severity.Associations between
habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24
patients with mild-moderate asthma and 18 matched control subjects). Sensewear
Armband was used to measure PA and metabolic equivalent of tasks (METs)
continuously over 4 days, while body composition was measured by bioelectrical
impedance analysis. Respiratory functions were also assessed in all study
participants.FM and FFM were comparable in mild-moderate asthmatics and controls,
but PA was lower in asthmatics and it was negatively correlated with FM and
positively with the FFM marker body cell mass in all study subjects (P < 0.05).
Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and
lower PA, METs, steps number/die, and forced expiratory volume in the 1st second
(FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA,
n = 12).This pilot study assesses that in mild-moderate asthma patients, lower PA
is associated with higher FM and higher disease severity. The current results
support enhancement of habitual PA as a potential tool to limit FM accumulation
and potentially contribute to preserve pulmonary function in moderate asthma,
considering the physical inactivity a strong risk factor for asthma worsening.
PMID- 27495093
TI - Comparison of a tube-holder (Rescuefix) versus tape-tying for minimizing double
lumen tube displacement during lateral positioning in thoracic surgery: A
prospective, randomized controlled study.
AB - BACKGROUND: Double-lumen endotracheal tubes (DLTs) are often displaced during
change from the supine to the lateral decubitus position. The aim of this study
was to determine whether Rescuefix, a recently developed tube-holder device, is
more effective than the traditional tape-tying method for tube security during
lateral positioning. METHODS: Patients were randomly assigned to a Rescuefix (R)
group (n = 22) or a tape (T) group (n = 22). After intubation with a left-sided
DLT and adjustment of the appropriate DLT position using a fiberoptic
bronchoscope, the DLT was fixed firmly at the side of the mouth by either
Rescuefix or Durapore tape. "Tracheal depth" (from the tracheal carina to the
elbow connector of the DLT) and "bronchial depth" (from the left bronchial carina
to the elbow connector of the DLT) were measured in the supine position using the
fiberoptic bronchoscope. After positional change, tracheal and bronchial depths
were measured as described above. As the primary endpoint, displacement of the
DLT during positional change was evaluated by obtaining the difference in depths
measured when the patient was in the supine and lateral decubitus positions. In
addition, after lateral positioning of the patient, any requirement for
repositioning the DLT was recorded. RESULTS: After lateral positioning, there
were no significant differences in changes in tracheal and bronchial depths
between the groups (tracheal depth 6.1 +/- 4.4 mm [R group] and 9.1 +/- 5.6 mm [T
group], P = 0.058; bronchial depth 6.5 +/- 4.4 mm [R group], and 8.5 +/- 4.6 mm
[T group], P = 0.132). Although the amount of change in tracheal and bronchial
depths was not different between the groups, the need to reposition the DLT was
significantly lower in the R group than in the T group (32% vs 68%, P = 0.016).
CONCLUSION: This study demonstrated that use of Rescuefix did not reduce the
amount of DLT displacement, but it did significantly lower the incidence of DLT
repositioning compared with the tape-tying method. Therefore, Rescuefix appears
to be an effective alternative to minimizing DLT displacement during lateral
positioning in thoracic surgery. TRIAL REGISTRATION: http://cris.nih.go.kr
identifier: KCT0001949.
PMID- 27495094
TI - Early postoperative albumin level following total knee arthroplasty is associated
with acute kidney injury: A retrospective analysis of 1309 consecutive patients
based on kidney disease improving global outcomes criteria.
AB - Hypoalbuminemia has been reported to be an independent risk factor for acute
kidney injury (AKI). However, little is known about the relationship between the
albumin level and the incidence of AKI in patients undergoing total knee
arthroplasty (TKA). The aim of our study was to assess incidence and risk factors
for AKI and to evaluate the relationship between albumin level and AKI following
TKA.The study included a retrospective review of medical records of 1309
consecutive patients who underwent TKA between January 2008 and December 2014.
The patients were divided into 2 groups according to the lowest serum albumin
level within 2 postoperative days (POD2_alb level < 3.0 g/dL vs >=3.0 g/dL).
Multivariate logistic regression analysis was used to assess risk factors for
AKI. A comparison of incidence of AKI, hospital stay, and overall mortality in
the 2 groups was performed using propensity score analysis.Of 1309 patients, 57
(4.4%) developed AKI based on Kidney Disease Improving Global Outcomes criteria.
Factors associated with AKI included age (odds ratio [OR] 1.05; 95% confidence
interval [CI] 1.01-1.09; P = 0.030), diabetes (OR 3.12; 95% CI 1.65-5.89; P <
0.001), uric acid (OR 1.51; 95% CI 1.26-1.82; P < 0.001), beta blocker use (OR
2.65; 95% CI 1.48-4.73; P = 0.001), diuretics (OR 16.42; 95% CI 3.08-87.68; P =
0.001), and POD2_alb level < 3.0 g/dL (OR 1.92; 95% CI 1.09-3.37; P = 0.023).
After propensity score analysis, POD2_alb level<3.0 g/dL was associated with AKI
occurrence (OR 1.82; 95% CI 1.03-3.24, P = 0.041) and longer hospital stay (P =
0.001).In this study, we demonstrated that POD2_alb level<3.0 g/dL was an
independent risk factor for AKI and lengthened hospital stay in patients
undergoing TKA.
PMID- 27495095
TI - Washed cell salvage in surgical patients: A review and meta-analysis of
prospective randomized trials under PRISMA.
AB - BACKGROUND: Cell salvage is commonly used as part of a blood conservation
strategy. However concerns among clinicians exist about the efficacy of
transfusion of washed cell salvage. METHODS: We performed a meta-analysis of
randomized controlled trials in which patients, scheduled for all types of
surgery, were randomized to washed cell salvage or to a control group with no
cell salvage. Data were independently extracted, risk ratio (RR), and weighted
mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data
were pooled using a random effects model. The primary endpoint was the number of
patients exposed to allogeneic red blood cell (RBC) transfusion. RESULTS: Out of
1140 search results, a total of 47 trials were included. Overall, the use of
washed cell salvage reduced the rate of exposure to allogeneic RBC transfusion by
a relative 39% (RR = 0.61; 95% CI 0.57 to 0.65; P < 0.001), resulting in an
average saving of 0.20 units of allogeneic RBC per patient (weighted mean
differences [WMD] = -0.20; 95% CI -0.22 to -0.18; P < 0.001), reduced risk of
infection by 28% (RR = 0.72; 95% CI 0.54 to 0.97; P = 0.03), reduced length of
hospital stay by 2.31 days (WMD = -2.31; 95% CI -2.50 to -2.11; P < 0.001), but
did not significantly affect risk of mortality (RR = 0.92; 95% CI 0.63 to 1.34; P
= 0.66). No statistical difference could be observed in the number of patients
exposed to re-operation, plasma, platelets, or rate of myocardial infarction and
stroke. CONCLUSIONS: Washed cell salvage is efficacious in reducing the need for
allogeneic RBC transfusion and risk of infection in surgery.
PMID- 27495096
TI - Vertebroplasty and balloon kyphoplasty versus conservative treatment for
osteoporotic vertebral compression fractures: A meta-analysis.
AB - OBJECTIVE: Although the majority of available evidence suggests that
vertebroplasty and kyphoplasty can relieve pain associated with vertebral
compression fractures (VCFs) and improve function, some studies have suggested
results are similar to those of placebo. The purpose of this meta-analysis was to
compare the outcomes of vertebroplasty and kyphoplasty with conservative
treatment in patients with osteoporotic VCFs. METHODS: Medline, Cochrane, and
Embase databases were searched until January 31, 2015 using the keywords:
vertebroplasty, kyphoplasty, compression fracture, osteoporotic, and
osteoporosis. Inclusion criteria were randomized controlled trials (RCTs) in
which patients with osteoporosis, and VCFs were treated with
vertebroplasty/kyphoplasty or conservative management. Outcome measures were
pain, function, and quality of life. Standardized differences in means were
calculated as a measure of effect size. MAIN RESULTS: Ten RCTs were included. The
total number of patients in the treatment and control groups was 626 and 628,
respectively, the mean patient age ranged from 64 to 80 years, and the majority
was female. Vertebroplasty/kyphoplasty was associated with greater pain relief
(pooled standardized difference in means = 0.82, 95% confidence interval [CI]:
0.374-1.266, P < 0.001) and a significant improvement in daily function (pooled
standardized difference in means = 1.273, 95% CI: 1.028-1.518, P < 0.001) as
compared with conservative treatment. The pooled estimate indicated
vertebroplasty/kyphoplasty was associated with higher quality of life (pooled
standardized difference in means = 1.545, 95% CI: 1.293-1.798, P < 0.001).
Subgroup analysis of 8 vertebroplasty studies and 2 kyphoplasty studies that
reported pain data, however, indicated that vertebroplasty provided greater pain
relief than conservative treatment but kyphoplasty did not. CONCLUSION:
Vertebroplasty may provide better pain relief than balloon kyphoplasty in
patients with osteoporotic VCFs, both may improve function, and their effect on
quality of life is less clear.
PMID- 27495097
TI - Safety and efficacy of a 6-month home-based exercise program in patients with
facioscapulohumeral muscular dystrophy: A randomized controlled trial.
AB - BACKGROUND: Previous randomized controlled trials investigating exercise training
programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and
of short duration only. This study assessed the safety and efficacy of a 6-month
home-based exercise training program on fitness, muscle, and motor function in
FSHD patients. METHODS: Sixteen FSHD patients were randomly assigned to training
(TG) and control (CG) groups (both n = 8) in a home-based exercise intervention.
Training consisted of cycling 3 times weekly for 35 minutes (combination of
strength, high-intensity interval, and low-intensity aerobic) at home for 24
weeks. Patients in CG also performed an identical training program (CTG) after 24
weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured
every 6 weeks. The principal secondary outcomes were maximal quadriceps strength
(MVC) and local quadriceps endurance every 12 weeks. Other outcome measures
included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6
minute walking distance every 12 weeks, and muscle characteristics from vastus
lateralis biopsies taken pre- and postintervention. RESULTS: The compliance rate
was 91% in TG. Significant improvements with training were observed in the VO2
peak (+19%, P = 0.002) and MAP by week 6 and further to week 24. Muscle
endurance, MVC, and 6-minute walking distance increased and experienced fatigue
decreased. Muscle fiber cross-sectional area and citrate synthase activity
increased by 34% (P = 0.008) and 46% (P = 0.003), respectively. Dystrophic
pathophysiologic patterns were not exacerbated. Similar improvements were
experienced by TG and CTG. CONCLUSIONS: A combined strength and interval cycling
exercise-training program compatible with patients' daily professional and social
activities leads to significant functional benefits without compromising muscle
tissue.
PMID- 27495098
TI - Effect of perioperative crystalloid or colloid fluid therapy on hemorrhage,
coagulation competence, and outcome: A systematic review and stratified meta
analysis.
AB - BACKGROUND: A meta-analysis concerning perioperative coagulation competence,
hemorrhage, and outcome was conducted including the use of hydroxyethyl starches
(HESs), dextran, or albumin versus administration of a crystalloid as control to
assess the efficacy and safety of colloids and crystalloids for fluid
administration during major elective surgery. Surgery was restricted to
cardiovascular and noncardiovascular surgery, and HESs were stratified to HES
130/0.4 and HES 200/0.5. METHODS: We searched Cochrane Central Register of
Controlled Trials, MEDLINE, ISI Web of Science, EMBASE, conference proceedings,
reference lists, and databases of ongoing trials. RESULTS: Thirty one primary
clinical randomized controlled trials included 2287 patients undergoing major
surgery from January 2000 to August 2015. The perioperative changes in
coagulation competence were measured by thromboelastography (TEG) maximum
amplitude (MA) in 9 studies administering crystalloids versus HES and in 4
studies administering albumin versus HES. All studies but 1 disclosed increased
reduction in TEG-MA following HES administration (P = 0.0001 and 0.0002). The
total loss of blood was reported in 17 studies in which crystalloids were
compared to HES and 12 studies reported increased blood loss after administration
of HES (P < 0.003). When administering albumin versus HES, 6 studies reported
reduced hemorrhage associated with albumin administration (P = 0.005).
Reoperation was not significantly reduced by the use of crystalloids, but may be
more frequent after HESs compared to albumin (P < 0.03). In this analysis, more
patients admitted to administration of HESs were exposed to decrease coagulation
competence, compared to perioperative crystalloids and albumin administration.
CONCLUSION: This stratified meta-analysis showed that increased blood loss was
found in noncardiovascular surgery among patients receiving HES compared with
crystalloids, followed by a marked reduction in TEG-MA, and infusion of 3rd
generation HES products did not influence the results significantly.
PMID- 27495099
TI - Comparison between whole mount tissue preparations and virtual tissue microarray
samples for measuring Ki-67 and apoptosis indices in human bladder cancer: A
cross-sectional study.
AB - Recent tissue microarray (TMA)-based studies have shown that cell proliferation-
and apoptosis-related biomarkers are associated with clinical outcomes in
patients with bladder urothelial carcinoma. However, little is known about the
differences in these biomarker measurements between whole mount tissue
preparations and TMAs. This study aimed to elucidate the discrepancy in the
measurements of Ki-67 indices (KIs) and apoptosis indices (AIs) between whole
mount tissue preparations and TMAs of bladder urothelial carcinoma samples.Whole
mount tissue preparations for Ki-67 immunohistochemistry and terminal
deoxynucleotidyl transferase dUTP nick end labeling were made from 30 patients
who underwent transurethral resection of bladder urothelial carcinoma. Digital
microscopy-assisted virtual TMAs, consisting of 3 small round areas (1 or 0.6 mm
in diameter), were generated from the same whole mount tissue preparations. The
measurement results in highly reactive areas of biomarkers were compared between
the whole mount tissue preparation- and the TMA-based methods. Bland-Altman plot
analysis, regression analysis, and Kendall tau were performed to investigate
differences in the measurement results, systematic biases, and correlations
between biomarkers.Although the Bland-Altman plot analysis demonstrated that
almost all the plots were within the limits of agreement, fixed biases were
detected in the 1- and 0.6-mm TMAs for the KI (0.181 and 0.222, respectively) and
the AI (0.055 and 0.063, respectively). Proportional biases were also detected in
the 1- and 0.6-mm TMAs for the AI (P < 0.001 and P < 0.001, respectively).
Furthermore, positive correlations between KIs and AIs were observed in whole
mount tissue preparations (r = 0.260, P = 0.044) and in the 1 mm TMAs (r = 0.375,
P = 0.004); however, no such correlation was observed in the 0.6 mm TMAs.Our
study suggests that the measurement results for certain biomarkers of bladder
urothelial carcinoma obtained from TMA-based samples can be susceptible to
systematic bias, and the lack of correlation between biomarkers cannot be avoided
as it is in whole mount tissue preparations. Virtual TMAs can help identify
systematic bias and establish a better sampling strategy prior to performing high
throughput TMAs for biomarker studies.
PMID- 27495100
TI - High plasma coenzyme Q10 concentration is correlated with good left ventricular
performance after primary angioplasty in patients with acute myocardial
infarction.
AB - Exogenous administration of coenzyme Q10 (CoQ10) has been shown in experimental
models to have a protective effect against ischemia-reperfusion injury. However,
it is unclear whether follow-up plasma CoQ10 concentration is prognostic of left
ventricular (LV) performance after primary balloon angioplasty in patients with
acute ST segment elevation myocardial infarction (STEMI).We prospectively
recruited 55 patients with STEMI who were treated with primary coronary balloon
angioplasty. Plasma CoQ10 concentrations were measured before primary angioplasty
(baseline) and 3 days, 7 days, and 1 month after STEMI using high-performance
liquid chromatography. Echocardiography was performed at baseline and at 6-month
follow-up. The control group comprised 54 healthy age- and sex-matched
volunteers.Serial circulating CoQ10 concentrations significantly decreased with
time in the STEMI group. The LV ejection fraction at 6-month follow-up positively
correlated with the 1-month plasma CoQ10 tertile. Higher plasma CoQ10
concentrations at 1 month were associated with favorable LV remodeling and
systolic function 6 months after STEMI. Multiple linear regression analysis
showed that changes in CoQ10 concentrations at 1-month follow-up were predictive
of LV systolic function 6 months after STEMI. Changes in CoQ10 concentrations
correlated negatively with baseline oxidized low-density lipoprotein and
fibrinogen concentrations and correlated positively with leukocyte mitochondrial
copy number at baseline.Patients with STEMI who had higher plasma CoQ10
concentrations 1 month after primary angioplasty had better LV performance at 6
month follow-up. In addition, higher plasma CoQ10 concentration was associated
with lower grade inflammatory and oxidative stress status. Therefore, plasma
CoQ10 concentration may serve as a novel prognostic biomarker of LV systolic
function after revascularization therapy for acute myocardial infarction.
PMID- 27495101
TI - The clinical application of "jetting suture" technique in annular repair under
microendoscopic discectomy: A prospective single-cohort observational study.
AB - To introduce a new designed suture technique in annular repair under the
microendoscopic discectomy (MED) surgery and to evaluate the clinical application
of the technique in annular repair under MED with at least 2-year follow-up
period.A new method of annular repair was designed and named "jetting suture"
technique. Thirty consecutive patients with lumbar disc herniation were enrolled
in the prospective single-cohort observational study. Patients were followed up
at intervals of preoperative, postoperative 1 week, 3 months, 6 months, 1 year,
and last follow-up. The clinical outcomes were evaluated by using Japanese
Orthopaedic Association (JOA) score, Oswestry Disability Index, and modified
Mcnab criteria.The procedure was successfully performed in all cases. No case
required conversion to an open procedure. The mean age of patients was 36.6
years. Average blood loss was 45.8 +/- 10.2 mL. The preoperative symptoms were
alleviated significantly after surgery. All the standardized measures improved
significantly at the last follow-up, including JOA score (10.1 to 26.6; P < 0.05)
and Oswestry Disability Index (75.3 to 9.6; P < 0.05). Improvement rate of JOA
score was 86.4%. Approximately 83.4% of patients reported good or excellent
outcomes based on modified Mcnab criteria. No postoperative complication and
recurrence of disc herniation was reported.The designed "jetting suture"
technique in annular repair under MED can be performed safely and effectively. It
could be a viable alternative to annular repair under lumbar discectomy.
PMID- 27495102
TI - Osteogenesis imperfecta and clubfoot-a rare combination: Case report and review
of the literature.
AB - BACKGROUND: Osteogenesis imperfecta (OI) is a rare congenital genetic
osteodystrophy, which has a prevalence of 1:20,000. OI is caused by the mutation
of the COL1A1/COL1A2 genes, leading to a deficit of quality and/or quantity in
the synthesis of procollagen-alpha type 1. Seven different forms of diverse
clinical entity have been classified by Sillence and Glorieux, although,
recently, up to 11 forms characterized by different genetic mutations have been
recognized. Patients with OI suffer from extreme bone fragility and osteoporosis,
which often predisposes them to frequent fractures. This paper presents the case
of a child with OI type IV who, at birth, was also diagnosed with a severe
clubfoot (congenital talipes equinovarus) grade III. Patient's mother also
suffers from OI type IV. METHODS: The treatment was started by placing femoro
podalic corrective casts, according to the Ponseti method, but some unexpected
problems occurred during this treatment. When the patient was 3 months of age, we
decided to correct the clubfoot before the time limit planned, performing a
bilateral posteromedial surgical release. RESULTS: Three weeks after surgery the
casts were removed and replaced with bilateral Spica cast-like braces. On the 6th
postoperative week, the patient began wearing Bebax corrective shoes, after 1
year ambidextrous orthopedic shoes. Now, he is 2 years old and has started to
walk properly without any orthesis. CONCLUSION: In the presence of an orthopedic
pathology associated with OI, it is recommended to manage the patient according
to the underlying pathology, always considering the bone fragility associated
with OI. The final surgical treatment to correct the clubfoot can be done
earlier, if necessary. In our opinion, this uncommon association between OI and
clubfoot is non-syndromic. This means that the two congenital diseases are not
necessarily included in a singular uncommon genetic syndrome, but the clubfoot
was caused by multifactorial causes, especially by both the mother's
bisphosphonate drug therapy and the amniocentesis performed during her pregnancy
to drain polyhydramnios. In our analysis, those environmental factors could have
interacted with an already altered genetic substratum, contributing to develop
this rare combination of congenital disorders.
PMID- 27495103
TI - Improving the utility of the Brunnstrom recovery stages in patients with stroke:
Validation and quantification.
AB - The Brunnstrom recovery stages (the BRS) consists of 2 items assessing the
poststroke motor function of the upper extremities and 1 assessing the lower
extremities. The 3 items together represent overall motor function. Although the
BRS efficiently assesses poststroke motor functions, a lack of rigorous
examination of the psychometric properties restricts its utility. We aimed to
examine the unidimensionality, Rasch reliability, and responsiveness of the BRS,
and transform the raw sum scores of the BRS into Rasch logit scores once the 3
items fitted the assumptions of the Rasch model.We retrieved medical records of
the BRS (N = 1180) from a medical center. We used Rasch analysis to examine the
unidimensionality and Rasch reliability of both upper-extremity items and the 3
overall motor items of the BRS. In addition, to compare their responsiveness for
patients (n = 41) assessed with the BRS and the Stroke Rehabilitation Assessment
of Movement (STREAM) on admission and at discharge, we calculated the effect size
(ES) and standardized response mean (SRM).The upper-extremity items and overall
motor items fitted the assumptions of the Rasch model (infit/outfit mean square =
0.57-1.40). The Rasch reliabilities of the upper-extremity items and overall
motor items were high (0.91-0.92). The upper-extremity items and overall motor
items had adequate responsiveness (ES = 0.35-0.41, SRM = 0.85-0.99), which was
comparable to that of the STREAM (ES = 0.43-0.44, SRM = 1.00-1.13).The results of
our study support the unidimensionality, Rasch reliability, and responsiveness of
the BRS. Moreover, the BRS can be transformed into an interval-level measure,
which would be useful to quantify the extent of poststroke motor function, the
changes of motor function, and the differences of motor functions in patients
with stroke.
PMID- 27495104
TI - Probiotics for prevention and treatment of respiratory tract infections in
children: A systematic review and meta-analysis of randomized controlled trials.
AB - BACKGROUND: Respiratory tract infections (RTIs) represent one of the main health
problems in children. Probiotics are viable bacteria that colonize the intestine
and affect the host intestinal microbial balance. Accumulating evidence suggests
that probiotic consumption may decrease the incidence of or modify RTIs. The
authors systematically reviewed data from randomized controlled trials (RCTs) to
investigate the effect of probiotic consumption on RTIs in children. METHODS:
MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science were systematically
searched for RCTs regarding the effect of probiotics on RTIs in children. The
outcomes included number of children experienced with at least 1 RTI episode,
duration of illness episodes, days of illness per subject, and school/day care
absenteeism due to infection. A random-effects model was used to calculate pooled
relative risks, or mean difference (MD) with the corresponding 95% confidence
interval (CI). RESULTS: A total of 23 trials involving 6269 children were
eligible for inclusion in the systematic review. None of the trials showed a high
risk of bias. The quality of the evidence of outcomes was moderate. The age range
of subjects was from newborn to 18 years. The results of meta-analysis showed
that probiotic consumption significantly decreased the number of subjects having
at least 1 RTI episode (17 RCTs, 4513 children, relative risk 0.89, 95% CI 0.82
0.96, P = 0.004). Children supplemented with probiotics had fewer numbers of days
of RTIs per person compared with children who had taken a placebo (6 RCTs, 2067
children, MD -0.16, 95% CI -0.29 to 0.02, P = 0.03), and had fewer numbers of
days absent from day care/school (8 RCTs, 1499 children, MD -0.94, 95% CI -1.72
to -0.15, P = 0.02). However, there was no statistically significant difference
of illness episode duration between probiotic intervention group and placebo
group (9 RCTs, 2817 children, MD -0.60, 95% CI -1.49 to 0.30, P = 0.19).
CONCLUSION: Based on the available data and taking into account the safety
profile of RCTs, probiotic consumption appears to be a feasible way to decrease
the incidence of RTIs in children.
PMID- 27495105
TI - Carotid plaque is a new risk factor for peripheral vestibular disorder: a
retrospective cohort study.
AB - Many chronic diseases are associated with dizziness or vertigo, as is peripheral
vestibular disorder (PVD). Although carotid plaque development is linked to
atherosclerosis, it is unclear whether such plaques can lead to the development
of PVD. We therefore conducted this study to investigate the presence of an
association between carotid plaque and new PVD events.In this retrospective
study, we consecutively enrolled 393 patients >=20 years old who had been treated
for chronic diseases such as hypertension, dyslipidemia, and diabetes mellitus
for >=6 months at a primary care clinic (Oki Clinic, Japan) between November 2011
and March 2013. Carotid plaque presence was measured with high-resolution
ultrasonography for all patients. During a 1-year follow-up period, an
otorhinolaryngologist diagnosed and reported any new PVD events (the main end
point). Hazard ratios (HRs) and 95% confidence intervals (CIs) for new PVD
occurrence were estimated using the Cox proportional hazard regression model.The
mean age of the participants was 65.5 years; 33.8% were men, and 12.7%, 82.4%,
and 93.1% had diabetes mellitus, hypertension, and dyslipidemia, respectively.
There were 76 new PVD events; patients with carotid plaque had a greater risk of
such events (crude HR: 3.25; 95% CI: 1.62-6.52) compared to those without carotid
plaque. This risk was even higher after adjusting for traditional risk factors
for atherosclerosis (adjusted HR: 4.41; 95% CI: 1.75-11.14).Carotid plaques are
associated with an increased risk of new PVD events.
PMID- 27495106
TI - The thromboelastometric discrepancy between septic and trauma induced
disseminated intravascular coagulation diagnosed by the scoring system from the
Japanese association for acute medicine.
AB - The aim of this study is to evaluate the hematological differences between septic
and traumatic disseminated intravascular coagulation (DIC) using the rotational
thromboelastometry (ROTEM).This retrospective study includes all sepsis or severe
trauma patients transported to our emergency department who underwent ROTEM from
2013 to 2014. All patients were divided into 2 groups based on the presence of
DIC diagnosed by the Japanese Association for Acute Medicine (JAAM) DIC score. We
statistically analyzed the demographics, clinical characteristics, laboratory
data, ROTEM findings (EXTEM and FIBTEM), and outcome.Fifty-seven patients (30
sepsis and 27 severe trauma) were included in primary analysis. Sepsis cases were
significantly older and had higher systemic inflammatory response syndrome (SIRS)
scores, whereas there were no significant differences in other parameters
including Acute Physiology and Chronic Health Evaluation (APACHE) II score,
sequential organ failure assessment (SOFA) score. Twenty-six patients (14 sepsis
and 12 severe trauma) were diagnosed with DIC. The Septic DIC (S-DIC) group was
significantly older and had higher DIC scores than the traumatic DIC (T-DIC)
group. Hematologic examination revealed significantly higher CRP, fibrinogen,
lower FDP, DD, and higher FDP/DD ratio were found in the S-DIC group in
comparison with the T-DIC group. ROTEM findings showed that the A10, A20, and MCF
in the FIBTEM test were significantly higher in the S-DIC group. However, no
statistical differences were confirmed in the LI30, LI45, and ML in EXTEM
test.The plasma fibrinogen level and fibrinogen based clot firmness in whole
blood test revealed statistical significance between septic and traumatic DIC
patients.
PMID- 27495107
TI - A negative nontreponemal and/or specific antitreponemal IgM test does not exclude
active infectious syphilis: evidence from a rabbit infectivity test: A case
report.
AB - BACKGROUND: The diagnostic criteria for active infectious syphilis in the clinic
are important matter of controversy and debate. So far, clinicians habitually do
use the negative results of the nontreponemal and/or the specific antitreponemal
IgM as the evidences of disease-free or active infection-free status. METHOD: We
present a case study involving a patient who was admitted to Zhongshan Hospital
because of cerebral infarct. Clinical examination indicated he had a history of
latent syphilis with negative nontreponemal and specific antitreponemal IgM
tests. The cerebrospinal fluid sample from the patient was inoculated into
seronegative New Zealand rabbit. RESULTS: Motile Treponema pallidum was detected
by a rabbit infectivity test in the patient's cerebrospinal fluid. This syphilis
strain was confirmed by DNA subtyping form of "centers for disease control
subtype/tp0548 sequence type", and the strain type was 14d/f. Treatment with
benzathine penicillin provided no apparent benefit, but treatment with aqueous
crystalline penicillin G, especially recommended for neurosyphilis, led to
disease regression. No evidence of cerebral infarct was observed during a 2-year
follow-up period. CONCLUSION: The definitive differential diagnosis of active
infectious syphilis should be reconsidered. Moreover, selecting the appropriate
penicillin preparation is important because T pallidum can reside in sequestered
sites. It is necessary to treat a patient with known invasion of the central
nervous system with aqueous crystalline penicillin G, if previous treatment for
syphilis failed and patients had some clinical neurological presentation that is
otherwise unexplained, but that could represent neurosyphilis. Additional studies
are needed to confirm the results in other syphilis patients.
PMID- 27495108
TI - ITRAQ-based quantitative proteomics reveals apolipoprotein A-I and transferrin as
potential serum markers in CA19-9 negative pancreatic ductal adenocarcinoma.
AB - Currently the diagnosis of pancreatic ductal adenocarcinoma (PDAC) relies on CA19
9 and radiological means, whereas some patients do not have elevated levels of
CA19-9 secondary to pancreatic cancer. The purpose of this study was to identify
potential serum biomarkers for CA19-9 negative PDAC.A total of 114 serum samples
were collected from 3 groups: CA19-9 negative PDAC patients (n = 34), CA19-9
positive PDAC patients (n = 44), and healthy volunteers (n = 36), whereas the
first 12 samples from each group were used for isobaric tags for relative and
absolute quantitation (iTRAQ) analysis. Thereafter, candidate biomarkers were
selected for validation by enzyme-linked immunosorbent assay (ELISA) with the
rest specimens.Using the iTRAQ approach, a total of 5 proteins were identified as
significantly different between CA19-9 negative PDAC patients and healthy
subjects according to our defined criteria. Apolipoprotein A-I (APOA-I) and
transferrin (TF) were selected to validate the proteomic results by ELISA in a
further 78 serum specimens. It revealed that TF significantly correlated with the
degree of histological differentiation (P = 0.042), and univariate and
multivariate analyses indicated that TF is an independent prognostic factor for
survival (hazard ratio, 0.302; 95% confidence interval, 0.118-0.774; P = 0.013)
of patients with PDAC after curative surgery.ITRAQ-based quantitative proteomics
revealed that APOA-I and TF may be potential CA19-9 negative PDAC serum markers.
PMID- 27495109
TI - Altered structural and functional connectivity between the bilateral primary
motor cortex in unilateral subcortical stroke: A multimodal magnetic resonance
imaging study.
AB - A large number of functional imaging studies have focused on the understanding of
motor-related neural activities after ischemic stroke. However, the knowledge is
still limited in the structural and functional changes of the interhemispheric
connections of the bilateral primary motor cortices (M1s) and their potential
influence on motor function recovery following stroke.Twenty-four stroke patients
with right hemispheric subcortical infarcts and 25 control subjects were
recruited to undergo multimodal magnetic resonance imaging examinations.
Structural impairments between the bilateral M1s were measured by fractional
anisotropy. Functional changes of the bilateral M1s were assessed via M1-M1
resting-state functional connectivity. Task-evoked activation analysis was
applied to identify the roles of the bilateral hemispheres in motor function
recovery. Compared with control subjects, unilateral subcortical stroke patients
revealed significantly decreased fractional anisotropy and functional
connectivity between the bilateral M1s. Stroke patients also revealed higher
activations in multiple brain regions in both hemispheres and that more regions
were located in the contralesional hemisphere.This study increased our
understanding of the structural and functional alterations between the bilateral
M1s that occur in unilateral subcortical stroke and provided further evidence for
the compensatory role played by the contralesional hemisphere for these
alterations during motor function recovery.
PMID- 27495110
TI - Association between comorbid conditions and BADL/IADL disability in hypertension
patients over age 45: Based on the China health and retirement longitudinal study
(CHARLS).
AB - Hypertension usually coexists with other chronic conditions and can cause
disability in relation to activities of daily living. We examined the association
between the number and categories of comorbid conditions and disability affecting
activities of daily living in hypertension patients.The data were collected from
the 2013 follow-up survey of the China Health and Retirement Longitudinal Study
(CHARLS), which contains information about chronic conditions and disability.
Additionally, socio-demographic characteristics of 3754 hypertension patients
aged 45 and older were included in this study. Comorbid conditions included
dyslipidemia, stroke, and 12 other chronic conditions. Disability in relation to
activities of daily living was assessed using the basic activities of daily
living (BADL) and the instrumental activities of daily living (IADL) instruments.
Differences in BADL/IADL disability among patients with different comorbid
conditions were compared using the chi-square test, and the influence of chronic
conditions and socio-demographic characteristics on BADL/IADL disability was
analyzed using logistic models.Without considering the influence of specific
chronic conditions on BADL/IADL, hypertension patients with additional comorbid
conditions were more likely to suffer from BADL/IADL disability. When considering
the effect of specific chronic conditions, the number of comorbid conditions did
not significantly influence BADL/IADL disability. Dyslipidemia, chronic lung
disease, stroke, memory-related diseases, and arthritis/rheumatism were
associated with BADL disability. Chronic lung diseases, heart diseases, stroke,
stomach/digestive system diseases, emotional/nervous/psychiatric problems, memory
related diseases, arthritis/rheumatism, and asthma were associated with IADL
disability. Additionally, female, people with lower education level, people
living in village, and people living in middle and western China were more likely
suffer from BADL/IADL disability.Comorbid conditions were associated with
disability in activities of daily living in hypertension patients aged 45 and
older. The specific comorbid conditions had a stronger effect on disability in
activities of daily living than the number of comorbid conditions. In addition,
we should pay attention to socioeconomic factors related to disability.
PMID- 27495112
TI - Zebrafish Danio rerio as a model to study the immune response against infection
with Ichthyophthirius multifiliis.
PMID- 27495113
TI - Making Judgments: How Blame Mediates the Influence of Rape Myth Acceptance in
Police Response to Sexual Assault.
AB - As research continues to describe negative experiences and high case attrition
within sexual assault cases reported to the police, it is important to better
understand the role of first-responding police officers. This study surveyed a
sample of sworn police officers ( N = 174) from one department in a midsized city
in the Great Lakes region to examine the effect of individual police officer
characteristics, rape myth acceptance (RMA), attributions of blame, and case
characteristics from a hypothetical vignette, on officer perceptions of a "good"
case and behavioral intentions. Results found that although RMA predicts both
perceptions of the case and behavioral intentions to respond in ways indicative
of perceived seriousness, RMA is mediated by attributions of suspect blame.
Victim alcohol use was found to decrease an officer's likelihood of responding
more vigorously, showing less likelihood of calling a detective or arresting the
suspect, if identified. Future research should begin to connect not only case
characteristics but also individual police officer characteristics, attitudes,
and attributions of blame, with real case outcomes, in addition to hypothetical
scenarios.
PMID- 27495114
TI - The Nonlinear Effect of Informal Social Control on Repeat Intimate Partner
Violence Victimization.
AB - Prior research has examined the effects of neighborhood context on intimate
partner violence (IPV) with mixed results. While most studies find that
neighborhood disadvantage is positively associated with risk of IPV, the effects
are less consistent for characteristics such as social ties and informal social
control. One possible explanation for these mixed findings draws from theoretical
and empirical literature arguing that a high level of collective efficacy can aid
in the control of criminal behavior, but it can also deter residents from acting
against crime committed by neighbors. This suggests the possibility of a
nonlinear effect of collective efficacy where the risk of IPV may be high in
areas with very low levels of collective efficacy because of the inability of
neighborhoods to collectively control residents, but it may also be high in areas
with very high levels of collective efficacy where residents are less willing to
report on the criminal behavior of fellow residents. We test this possibility
using survey data for female victims of IPV in Chicago merged with neighborhood
characteristics. Findings suggest that the risk of repeat victimization is
highest in areas with either very high or very low levels of informal social
control.
PMID- 27495111
TI - Clinical significance of smear positivity for acid-fast bacilli after >=5 months
of treatment in patients with drug-susceptible pulmonary tuberculosis.
AB - Patients with pulmonary tuberculosis (TB) with acid-fast bacilli (AFB)-positive
sputum smear at 5 months or later during treatment are considered to be cases of
treatment failure according to World Health Organization guidelines. This study
evaluated the proportion, clinical characteristics, and significance of positive
sputum smears after >=5 months of standard treatment in patients with drug
susceptible pulmonary TB.This was a retrospective cohort study of 1611 patients
with culture-confirmed drug-susceptible pulmonary TB who received standard anti
TB treatment from January 2009 to February 2014. Forty-one patients (2.5%) who
were smear-positive after >=5 months of treatment and 123 age- and sex-matched
control patients were evaluated.Among the 41 smear-positive patients, culture of
the sputum specimens yielded Mycobacterium tuberculosis (MTB) in 1 patient
(2.4%), nontuberculous mycobacteria (NTM) in 7 (17.1%), and no growth in the
remaining 33 patients (80.5%). Treatment was successfully completed in 40
patients (97.6%) with prolongation of the continuation phase regimens without
change to second-line anti-TB treatment. In patients with smear positivity after
>=5 months of treatment compared with controls, cavitation on chest radiographs
(53.7% vs. 25.2%, P = 0.001), bilateral involvement (51.2% vs. 30.1%, P = 0.01)
and combined pleural effusion (26.8% vs. 10.6%, P = 0.01) were found more
frequently at the time of treatment initiation, and paradoxical response occurred
more commonly (19.5% vs. 3.3%, P = 0.002) during treatment.Smear-positive sputum
after >=5 months of standard anti-TB treatment was mainly because of nonviable
MTB bacilli or NTM in patients with drug-susceptible pulmonary TB. AFB smear
alone should not be used to assess treatment failure and careful examination of
microbiologic status, including culture and drug susceptibility testing, is
needed before making changes to retreatment regimens or empirical second-line
anti-TB regimens in these patients.
PMID- 27495115
TI - Gestational weight gain and fetal growth in underweight women.
AB - BACKGROUND: Despite the current obesity epidemic, maternal underweight remains a
common occurrence with potential adverse perinatal outcomes. METHODS: We aimed to
investigate the relationship between weight gain during pregnancy, and fetal
growth in underweight women with low and late fertility. Women body mass index
(BMI), defined according to the World Health Organization's definition,
gestational weight gain (GWG), defined by the Institute of Medicine and National
Research Council and neonatal birth weight were prospectively collected at
maternity ward of Policlinico Abano Terme (Italy) in 793 consecutive at term,
uncomplicated deliveries. RESULTS: Among those, 96 (12.1 %) were categorized as
underweight (BMI < 18.5 kg/m(2)), 551 (69.5 %) as normal weight, 107 (13.4 %) as
overweight, and 39 (4.9 %) as obese, respectively. In all mother groups, GWG was
within the range recommended by IOM 2009 guidelines. However, underweight women
gained more weight in pregnancy (12.8 +/- 3.9 kg) in comparison to normal weight
(12.3 +/- 6.7 kg) and overweight (11.0 +/- 4.7 kg) women and their GWG was
significantly higher (p < 0.001) with respect to obese women 5.8 +/- 6.1 kg). In
addition, offspring of underweight women were comparable in size at birth to
offspring of normal weight women, whereas they were significantly lighter to
offspring of both overweight and obese women. CONCLUSIONS: Pre-pregnancy
underweight does not impact birth weight of healthy, term neonates in presence of
normal GWG. Presumably, medical or personal efforts to reach 'optimal' GWG could
be a leading choice for many women living in industrialized and in low-income
countries.
PMID- 27495116
TI - Upregulated expression of CCR3 in rheumatoid arthritis and CCR3-dependent
activation of fibroblast-like synoviocytes.
AB - It is recognized that CC chemokine receptor 3 (CCR3) is associated with numerous
inflammatory conditions and fibroblast-like synoviocyte (FLS) invasiveness
correlates with articular damage in rheumatoid arthritis (RA). However, little is
known of the expression and action of CCR3 on FLS in RA. In the present study, we
investigated the expression of CCR3 on dispersed synovial tissue and peripheral
blood cells in RA and influence of eotaxin-1 on FLS functions by using flow
cytometry analysis, FLS challenge, and real-time PCR techniques. The results
showed that approximately 7.0 % dispersed synovial cells are CCR3+ cells. Among
those CCR3+ cells, 38.1, 23.8, and 20.6 % cells are CD90+CD14-CD3- (representing
FLS), CD14+, and CD8+ cells, respectively, indicating that FLS is one of the
major populations of CCR3+ cells in the synovial tissue of RA. In peripheral
blood, CD14+ CCR3+ cells are elevated, but CD8+CCR3+ cells are reduced in RA. It
was found that eotaxin-1 induced upregulated expression of CCR3 and matrix
metalloproteinase (MMP)-9 messenger RNAs (mRNAs) in FLS. Since an antagonist of
CCR3 suppressed the action of eotaxin-1, the event appeared CCR3 dependent.
Moreover, we observed that interleukin (IL)-1beta induced markedly enhanced
eotaxin-1 release from FLS, but TNF-alpha reduced eotaxin-1 release at 12 and 24
h following incubation. In conclusion, enhanced expression of CCR3 on synovial
cells and increased levels of eotaxin-1 in plasma and synovial fluid (SF) of RA
indicate that CCR3-mediated mechanisms may play an important role in RA. Blockage
of eotaxin-1 provoked CCR3 and MMP-9 expression in FLS by antagonist of CCR3,
implicating that anti-CCR3 agents may have therapeutic use for RA.
PMID- 27495118
TI - Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and
Human Hepatocytes by High-Resolution Mass Spectrometry.
AB - Carfentanil is an ultra-potent synthetic opioid. No human carfentanil metabolism
data are available. Reportedly, Russian police forces used carfentanil and
remifentanil to resolve a hostage situation in Moscow in 2002. This alleged use
prompted interest in the pharmacology and toxicology of carfentanil in humans.
Our study was conducted to identify human carfentanil metabolites and to assess
carfentanil's metabolic clearance, which could contribute to its acute toxicity
in humans. We used Simulations Plus's ADMET PredictorTM and Molecular Discovery's
MetaSiteTM to predict possible metabolite formation. Both programs gave similar
results that were generally good but did not capture all metabolites seen in
vitro. We incubated carfentanil with human hepatocytes for up to 1 h and analyzed
samples on a Sciex 3200 QTRAP mass spectrometer to measure parent compound
depletion and extrapolated that to represent intrinsic clearance. Pooled primary
human hepatocytes were then incubated with carfentanil up to 6 h and analyzed for
metabolite identification on a Sciex 5600+ TripleTOF (QTOF) high-resolution mass
spectrometer. MS and MS/MS analyses elucidated the structures of the most
abundant metabolites. Twelve metabolites were identified in total. N-Dealkylation
and monohydroxylation of the piperidine ring were the dominant metabolic
pathways. Two N-oxide metabolites and one glucuronide metabolite were observed.
Surprisingly, ester hydrolysis was not a major metabolic pathway for carfentanil.
While the human liver microsomal system demonstrated rapid clearance by CYP
enzymes, the hepatocyte incubations showed much slower clearance, possibly
providing some insight into the long duration of carfentanil's effects.
PMID- 27495119
TI - Strategies to Determine Assay Format for the Assessment of Neutralizing Antibody
Responses to Biotherapeutics.
AB - Most biotherapeutics can elicit immune responses in dosed recipients generating
anti-drug antibodies (ADAs). Neutralizing antibodies (NAbs) are a subpopulation
of ADAs that can potentially impact patient safety and directly mediate loss of
drug efficacy by blocking the biological activity of a therapeutic product.
Therefore, NAb detection is an important aspect of immunogenicity assessment,
requiring sensitive and reliable methods reflective of the therapeutic mechanism
of action (MoA). Both cell-based and non cell-based assays are viable options for
NAb assessment. However, the scientific approach for the selection of a suitable
assay format (cell-based or non cell-based) for NAb assessment is not currently
well defined. In this manuscript, the authors summarize the design and utility of
cell-based and non cell-based NAb assays and recommend a NAb assay format
selection approach that relies on a combination of three factors. These include
(i) the therapeutic MoA, (ii) the evidence of desirable assay performance
characteristics, and (iii) risk of immunogenicity. The utility of correlating NAb
response with pharmacodynamic data is also discussed. The aim of this paper is to
provide a consistent strategy that will guide the selection of scientifically
justified assay formats capable of detecting clinically relevant NAbs for
biotherapeutics with varying MoAs and diverse complexity.
PMID- 27495117
TI - Challenges and Opportunities with Non-CYP Enzymes Aldehyde Oxidase,
Carboxylesterase, and UDP-Glucuronosyltransferase: Focus on Reaction Phenotyping
and Prediction of Human Clearance.
AB - Over the years, significant progress has been made in reducing metabolic
instability due to cytochrome P450-mediated oxidation. High-throughput metabolic
stability screening has enabled the advancement of compounds with little to no
oxidative metabolism. Furthermore, high lipophilicity and low aqueous solubility
of presently pursued chemotypes reduces the probability of renal excretion. As
such, these low microsomal turnover compounds are often substrates for non-CYP
mediated metabolism. UGTs, esterases, and aldehyde oxidase are major enzymes
involved in catalyzing such metabolism. Hepatocytes provide an excellent tool to
identify such pathways including elucidation of major metabolites. To predict
human PK parameters for P450-mediated metabolism, in vitro-in vivo extrapolation
using hepatic microsomes, hepatocytes, and intestinal microsomes has been
actively investigated. However, such methods have not been sufficiently evaluated
for non-P450 enzymes. In addition to the involvement of the liver, extrahepatic
enzymes (intestine, kidney, lung) are also likely to contribute to these
pathways. While there has been considerable progress in predicting metabolic
pathways and clearance primarily mediated by the liver, progress in
characterizing extrahepatic metabolism and prediction of clearance has been slow.
Well-characterized in vitro systems or in vivo animal models to assess drug-drug
interaction potential and intersubject variability due to polymorphism are not
available. Here we focus on the utility of appropriate in vitro studies to
characterize non-CYP-mediated metabolism and to understand the enzymes involved
followed by pharmacokinetic studies in the appropriately characterized surrogate
species. The review will highlight progress made in establishing in vitro-in vivo
correlation, predicting human clearance and avoiding costly clinical failures
when non-CYP-mediated metabolic pathways are predominant.
PMID- 27495120
TI - A Quantitative Review and Meta-Models of the Variability and Factors Affecting
Oral Drug Absorption-Part I: Gastrointestinal pH.
AB - This study aimed to conduct a quantitative meta-analysis for the values of, and
variability in, gastrointestinal (GI) pH in the different GI segments;
characterize the effect of food on the values and variability in these
parameters; and present quantitative meta-models of distributions of GI pH to
help inform models of oral drug absorption. The literature was systemically
reviewed for the values of, and the variability in, GI pH under fed and fasted
conditions. The GI tract was categorized into the following 10 distinct regions:
stomach (proximal, mid-distal), duodenum (proximal, mid-distal), jejunum and
ileum (proximal, mid, and distal small intestine), and colon (ascending,
transverse, and descending colon). Meta-analysis used the "metafor" package of
the R language. The time course of postprandial stomach pH was modeled using
NONMEM. Food significantly influenced the estimated meta-mean stomach and
duodenal pH but had no significant influence on small intestinal and colonic pH.
The time course of postprandial pH was described using an exponential model.
Increased meal caloric content increased the extent and duration of postprandial
gastric pH buffering. The different parts of the small intestine had
significantly different pH. Colonic pH was significantly different for descending
but not for ascending and transverse colon. Knowledge of GI pH is important for
the formulation design of the pH-dependent dosage forms and in understanding the
dissolution and absorption of orally administered drugs. The meta-models of GI pH
may also be used as part of semi-physiological pharmacokinetic models to
characterize the effect of GI pH on the in vivo drug release and
pharmacokinetics.
PMID- 27495121
TI - Internal carotid artery dissection coincides with celiac artery dissection.
PMID- 27495122
TI - Targeting bactoprenol-coupled cell envelope precursors.
AB - Targeting the bactoprenol-coupled cell wall precursor lipid II is a validated
antibacterial strategy. In this review, selected prototype lipid II-binding
antibiotics of different chemical classes are discussed. Although these compounds
attack the same molecular target, they trigger nuanced and diverse cellular
effects. Consequently, the mechanisms of antibacterial resistance and the
likelihood of resistance development may vary substantially.
PMID- 27495123
TI - Erratum to: The Simultaneous Occurrence of Histoplasmosis and Cryptococcal
Fungemia: A Case Report and Review of the Literature.
PMID- 27495124
TI - Passive protection effect of anti-Vibrio anguillarum IgY-encapsulated feed on
half-smooth tongue sole (Cynoglossus semilaevi) against V. anguillarum.
AB - Vibrio anguillarum is one of the most harmful pathogens associated with
hemorrhage septicemia syndrome in the half-smooth tongue sole (C. semilaevis) due
to its high virulence. In this study, we attempted to treat half-smooth tongue
sole with anti-V. anguillarum egg yolk powder to elicit a passive immunity
directly against V. anguillarum infection. Anti-V. anguillarum IgY was beta
cyclodextrin encapsulated in egg yolk powders as feed, which could avoid antibody
inactivation in the gastrointestinal tract of half-smooth tongue sole. The IgY
had an inhibiting effect on the infection of V. anguillarum in vitro. The
survival rate of half-smooth tongue sole fed with basal diet containing 15% anti
V. anguillarum egg yolk powder was 70% after 7 days post-V. anguillarum challenge
(10(7) CFU), which was significantly higher than those fed without anti-V.
anguillarum egg yolk powder. As well, the bacterial burden in blood, liver,
spleen and kidney was significantly lower in half-smooth tongue sole fed with
specific IgY than those fed with non-specific IgY. These results suggested that
pathogen-specific IgY may provide a valuable treatment for vibriosis infection
and can be a promising food additive.
PMID- 27495125
TI - A survey of flood disaster preparedness among hospitals in the central region of
Thailand.
AB - BACKGROUND: In 2011, Thailand was affected by the one of the worst flood
disasters in recent times. Hospitals in Thailand were faced with the challenge of
managing the health impacts from this natural disaster. The purpose of this study
was to assess flood disaster preparedness among hospitals in the central region
of Thailand. METHODS: A survey questionnaire was given to twenty-seven key people
responsible for hospital disaster preparedness that experienced disruptions to
health services (severely, moderately and slightly) during the flood disaster in
2011 in the central region of Thailand. RESULTS: Of the twenty-four participating
hospitals, not one had satisfied the standards in all the dimensions of flood
disaster preparedness. All respondent hospitals were deficiently prepared with
regard to surge capacity, the management of healthcare services and the
management of the supporting systems. The availability of supplies and equipment
were found to be in place but preparations were found to be inadequate in
organizing staff at all participating hospitals. Trained staff members regarding
disaster response were reported to be present in all respondent hospitals.
Hospitals that experienced slightly disruptions to their health services did not
elect to do any exercises to meet the set standards. None of the hospitals that
experienced slightly disruptions to their health services performed any
evaluation and improvement in terms of disaster preparedness. CONCLUSIONS: Many
hospitals were not up to standard in terms of disaster preparedness. Hospitals
should prioritize disaster preparedness to fulfill their responsibility during
crisis situations and improve their flood disaster preparedness.
PMID- 27495126
TI - Comparing patient outcomes for care delivered by advanced musculoskeletal
physiotherapists with other health professionals in the emergency department-A
pilot study.
AB - BACKGROUND: To compare advanced musculoskeletal physiotherapists with other
health professionals by measuring outcomes for patients presenting to the
emergency department with lower limb soft tissue injuries or acute low back pain.
METHODS: A prospective study was conducted (Lower limb soft tissue injury cohort,
n=88), (Acute low back pain cohort, n=29) at the emergency departments of two
urban hospitals. A univariate analysis was completed for a number of outcome
measures: Lower Extremity Functional Scale, Roland Morris Disability
Questionnaire, imaging requirements, Patient Satisfaction Questionnaire,
Numerical Pain Rating Scale and medication use. Data was obtained at discharge,
two weeks and six weeks post-discharge. RESULTS: Advanced musculoskeletal
physiotherapists ordered less imaging, had less opioids (lower limb soft tissue
injury) administered to patients, and patients' described equal or more
satisfaction when compared to another health professional (p<0.05). No
significant differences were found between groups for functional or pain related
outcomes in both cohorts (p>0.05). CONCLUSION: Advanced musculoskeletal
physiotherapists are less likely to order imaging, obtain similar outcomes
regarding pain medications and display equal or more patient satisfaction when
compared to other health professionals for patients presenting to the emergency
department with lower limb soft tissue injuries or acute low back pain.
PMID- 27495127
TI - Interspecific interference competition at the resource patch scale: do large
herbivores spatially avoid elephants while accessing water?
AB - Animals may anticipate and try to avoid, at some costs, physical encounters with
other competitors. This may ultimately impact their foraging distribution and
intake rates. Such cryptic interference competition is difficult to measure in
the field, and extremely little is known at the interspecific level. We tested
the hypothesis that smaller species avoid larger ones because of potential costs
of interference competition and hence expected them to segregate from larger
competitors at the scale of a resource patch. We assessed fine-scale spatial
segregation patterns between three African herbivore species (zebra Equus quagga,
kudu Tragelaphus strepsiceros and giraffe Giraffa camelopardalis) and a
megaherbivore, the African elephant Loxodonta africana, at the scale of water
resource patches in the semi-arid ecosystem of Hwange National Park, Zimbabwe.
Nine waterholes were monitored every two weeks during the dry season of a drought
year, and observational scans of the spatial distribution of all herbivores were
performed every 15 min. We developed a methodological approach to analyse such
fine-scale spatial data. Elephants increasingly used waterholes as the dry season
progressed, as did the probability of co-occurrence and agonistic interaction
with elephants for the three study species. All three species segregated from
elephants at the beginning of the dry season, suggesting a spatial avoidance of
elephants and the existence of costs of being close to them. However, contrarily
to our expectations, herbivores did not segregate from elephants the rest of the
dry season but tended to increasingly aggregate with elephants as the dry season
progressed. We discuss these surprising results and the existence of a trade-off
between avoidance of interspecific interference competition and other potential
factors such as access to quality water, which may have relative associated costs
that change with the time of the year.
PMID- 27495128
TI - Wound healing efficacy of a 660-nm diode laser in a rat incisional wound model.
AB - This study aimed to elucidate the optimum usage parameters of low reactive-level
laser therapy (LLLT) in a rat incisional wound model. In Sprague-Dawley rats,
surgical wounds of 15-mm length were made in the dorsal thoracic region. They
were divided into groups to receive 660-nm diode laser irradiation 24 h after
surgery at an energy density of 0 (control), 1, 5, or 10 J/cm2. Tissue sections
collected on postoperative day 3 were stained with hematoxylin-eosin and an
antibody for ED1 to determine the number of macrophages around the wound. Samples
collected on day 7 were stained with hematoxylin-eosin and observed via polarized
light microscopy to measure the area occupied by collagen fibers around the
wound; day 7 skin specimens were also subjected to mechanical testing to evaluate
tensile strength. On postoperative day 3, the numbers of macrophages around the
wound were significantly lower in the groups receiving 1 and 5 J/cm2 irradiation,
compared to the control and 10 J/cm2 irradiation groups (p < 0.01). The area
occupied by collagen fibers in day 7 was largest in 5 J/cm2 group, followed by 1
J/cm2 group, although this difference was not significant. The day 7 tensile test
demonstrated significantly greater rupture strength in healing tissues from 1 and
5 J/cm2 irradiation groups, compared to the control group (p < 0.05). Thus, LLLT
with a 660-nm diode laser with energy density of 1 and 5 J/cm2 enhanced wound
healing in a rat incisional wound model. However, a higher radiation energy
density yielded no significant enhancement.
PMID- 27495129
TI - Laser acupuncture causes thermal changes in small intestine meridian pathway.
AB - The acupuncture meridians represent the flow of corporal energy which contains
the acupuncture points. Laser acupuncture is a form of acupuncture stimulation by
the use of laser. Thermographic images represent the propagation of heat in micro
environmental systems. The objective of this study was to investigate the use of
thermographic images to document the changes on the small intestine meridian
(S.I.M.) when submitted to laser acupuncture. Another important issue regards to
the analysis of the flow direction if it is upward when stimulated by acupuncture
points. For the execution of this work, a laser acupuncture pen was used in
points of the meridian in the S.I.M. Two healthy male volunteers were selected
(18 and 60 years old, respectively), and doses of 576,92 J/cm2 with low-power
infrared laser equipment with a wavelength of 780 nm in the SI.3 and SI.19 points
were applied. An infrared thermal camera was used to measure the temperature of
the S.I.M. during the 6 min laser acupuncture pen stimulus. When the laser
acupuncture of both volunteers was conducted in the SI.3 point, it presented
hyper-radiation of the hemi face in the same side, far from the application site.
When this was applied in the SI.19 point, hyper-radiation in the same point and
temperature lowering at the end of the meridian were observed. The laser energy
caused thermal changes along the path of the S.I.M., distal, and proximal at the
same time, proving the existence of the S.I.M.
PMID- 27495130
TI - Photo-biomodulatory response of low-power laser irradiation on burn tissue repair
in mice.
AB - The present work reports the photo-biomodulatory effect of red (632.8 nm) and
near infrared (785 and 830 nm) lasers on burn injury in Swiss albino mice.
Animals were induced with a 15-mm full thickness burn injury and irradiated with
various fluences (1, 2, 3, 4, and 6 J/cm2) of each laser wavelength under study
having a constant fluence rate (8.49 mW/cm2). The size of the injury following
treatment was monitored by capturing the wound images at regular time intervals
until complete healing. Morphometric assessment indicated that the group treated
with 3-J/cm2 fluence of 830 nm had a profound effect on healing as compared to
untreated controls and various fluences of other wavelengths under study.
Histopathological assessment of wound repair on treatment with an optimum fluence
(3 J/cm2) of 830 nm performed on days 2, 6, 12, and 18 post-wounding resulted in
enhanced wound repair with migration of fibroblasts, deposition of collagen, and
neovascularization as compared to untreated controls. The findings of the present
study have clearly demonstrated that a single exposure of 3-J/cm2 fluence at 830
nm enhanced burn wound healing progression in mice, which is equivalent to 5 %
povidone iodine treatment (reference standard), applied on a daily basis till
complete healing.
PMID- 27495131
TI - Measuring inter-rater reliability for nominal data - which coefficients and
confidence intervals are appropriate?
AB - BACKGROUND: Reliability of measurements is a prerequisite of medical research.
For nominal data, Fleiss' kappa (in the following labelled as Fleiss' K) and
Krippendorff's alpha provide the highest flexibility of the available reliability
measures with respect to number of raters and categories. Our aim was to
investigate which measures and which confidence intervals provide the best
statistical properties for the assessment of inter-rater reliability in different
situations. METHODS: We performed a large simulation study to investigate the
precision of the estimates for Fleiss' K and Krippendorff's alpha and to
determine the empirical coverage probability of the corresponding confidence
intervals (asymptotic for Fleiss' K and bootstrap for both measures).
Furthermore, we compared measures and confidence intervals in a real world case
study. RESULTS: Point estimates of Fleiss' K and Krippendorff's alpha did not
differ from each other in all scenarios. In the case of missing data (completely
at random), Krippendorff's alpha provided stable estimates, while the complete
case analysis approach for Fleiss' K led to biased estimates. For shifted null
hypotheses, the coverage probability of the asymptotic confidence interval for
Fleiss' K was low, while the bootstrap confidence intervals for both measures
provided a coverage probability close to the theoretical one. CONCLUSIONS:
Fleiss' K and Krippendorff's alpha with bootstrap confidence intervals are
equally suitable for the analysis of reliability of complete nominal data. The
asymptotic confidence interval for Fleiss' K should not be used. In the case of
missing data or data or higher than nominal order, Krippendorff's alpha is
recommended. Together with this article, we provide an R-script for calculating
Fleiss' K and Krippendorff's alpha and their corresponding bootstrap confidence
intervals.
PMID- 27495132
TI - Development and validation of a loop mediated isothermal amplification (LAMP)
assay for the detection of Staphylococcus aureus in bovine mastitis milk samples.
AB - Staphylococcus (S.) aureus is one of the most important animal pathogens causing
bovine mastitis. Also, it is a major human pathogen that may produce a variety of
toxins which cause staphylococcal food poisoning. In the present study a LAMP
assay based on gene nuc to identify S. aureus was developed and validated. The
specificity of the LAMP assay was confirmed by using 70 S. aureus isolates and 21
non-S. aureus strains. The optimal temperature-time combination to amplify gene
nuc successfully was 65 degrees C and 30 min. The analytical sensitivity of the
developed LAMP assay was 0.26 pg of S. aureus DNA per reaction. The limit of
detection evaluated with milk spiked with S. aureus was 9 * 102 CFU mL-1. The
final results of this assay were available within less than 2 h. The present
study showed that the LAMP assay based on gene nuc appeared to be rapid and
simple, and could also be used to identify S. aureus isolates from mastitis milk
of dairy cows.
PMID- 27495133
TI - Trigeminal autonomic cephalgia caused by recurrent posterior scleritis.
AB - A 40-year-old woman presented with a side-locked headache with autonomic
features, which then switched sides before reverting to the original side. The
atypical features of side swapping, partial response to indometacin and abnormal
optic disc appearances ultimately led to a diagnosis of recurrent posterior
scleritis. We discuss the differential diagnosis of trigeminal autonomic
cephalgias and its secondary causes, and provide practical pointers for its
investigation and management.
PMID- 27495134
TI - Effect of inflammation on HDL structure and function.
AB - PURPOSE OF REVIEW: Studies have shown that chronic inflammatory disorders, such
as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis are
associated with an increased risk of atherosclerotic cardiovascular disease. The
mechanism by which inflammation increases cardiovascular disease is likely
multifactorial but changes in HDL structure and function that occur during
inflammation could play a role. RECENT FINDINGS: HDL levels decrease with
inflammation and there are marked changes in HDL-associated proteins. Serum
amyloid A markedly increases whereas apolipoprotein A-I, lecithin:cholesterol
acyltransferase, cholesterol ester transfer protein, paraoxonase 1, and
apolipoprotein M decrease. The exact mechanism by which inflammation decreases
HDL levels is not defined but decreases in apolipoprotein A-I production,
increases in serum amyloid A, increases in endothelial lipase and secretory
phospholipase A2 activity, and decreases in lecithin:cholesterol acyltransferase
activity could all contribute. The changes in HDL induced by inflammation reduce
the ability of HDL to participate in reverse cholesterol transport and protect
LDL from oxidation. SUMMARY: During inflammation multiple changes in HDL
structure occur leading to alterations in HDL function. In the short term, these
changes may be beneficial resulting in an increase in cholesterol in peripheral
cells to improve host defense and repair but over the long term these changes may
increase the risk of atherosclerosis.
PMID- 27495135
TI - Early nutrition, epigenetics, and cardiovascular disease.
AB - PURPOSE OF REVIEW: Here, we provide a summary of the current knowledge on the
impact of early life nutrition on cardiovascular diseases that have emerged from
studies in humans and experimental animal models. The involvement of epigenetic
mechanisms in the Developmental Origins of Health and Disease will be discussed
in relation to the implications for the heart and the cardiovascular system.
RECENT FINDINGS: Environmental cues, such as parental diet and a suboptimal in
utero environment can shape growth and development, causing long-lasting
cardiometabolic perturbations. Increasing evidence suggest that these effects are
mediated at the epigenomic level, and can be passed onto future generations. In
the last decade, epigenetic mechanisms (DNA methylation, histone modifications)
and RNA-based mechanisms (microRNAs, piRNAs, and tRNAs) have therefore emerged as
potential candidates for mediating inheritance of cardiometabolic diseases.
SUMMARY: The burden of obesity and associated cardiometabolic diseases is
believed to arise through interaction between an individual's genetics and the
environment. Moreover, the risk of developing poor cardiometabolic health in
adulthood is defined by early life exposure to pathological cues and can be
inherited by future generations, initiating a vicious cycle of transmission of
disease. Elucidating the molecular triggers of such a process will help tackle
and prevent the uncontrolled rise in obesity and cardiometabolic disease.
PMID- 27495136
TI - Biomarker-guided antibiotic use in primary care in resource-constrained
environments.
PMID- 27495138
TI - Response to Black R and Chin R's letter on our article "Epilepsy in children and
adolescents: Disease concepts, practical knowledge, and coping".
PMID- 27495139
TI - Fitness to drive - When all may not be as it seems.
PMID- 27495137
TI - Point-of-care C-reactive protein testing to reduce inappropriate use of
antibiotics for non-severe acute respiratory infections in Vietnamese primary
health care: a randomised controlled trial.
AB - BACKGROUND: Inappropriate antibiotic use for acute respiratory tract infections
is common in primary health care, but distinguishing serious from self-limiting
infections is difficult, particularly in low-resource settings. We assessed
whether C-reactive protein point-of-care testing can safely reduce antibiotic use
in patients with non-severe acute respiratory tract infections in Vietnam.
METHOD: We did a multicentre open-label randomised controlled trial in ten
primary health-care centres in northern Vietnam. Patients aged 1-65 years with at
least one focal and one systemic symptom of acute respiratory tract infection
were assigned 1:1 to receive either C-reactive protein point-of-care testing or
routine care, following which antibiotic prescribing decisions were made.
Patients with severe acute respiratory tract infection were excluded. Enrolled
patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone
interview was done blind to the intervention. Randomised assignments were
concealed from prescribers and patients but not masked as the test result was
used to assist treatment decisions. The primary outcome was antibiotic use within
14 days of follow-up. All analyses were prespecified in the protocol and the
statistical analysis plan. All analyses were done on the intention-to-treat
population and the analysis of the primary endpoint was repeated in the per
protocol population. This trial is registered under number NCT01918579. FINDINGS:
Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009
adults) were enrolled and randomised. One adult patient withdrew immediately
after randomisation. 1017 patients were assigned to receive C-reactive protein
point-of-care testing, and 1019 patients were assigned to receive routine care.
115 patients in the C-reactive protein point-of-care group and 72 patients in the
routine care group were excluded in the intention-to-treat analysis due to
missing primary endpoint. The number of patients who used antibiotics within 14
days was 581 (64%) of 902 patients in the C-reactive protein group versus 738
(78%) of 947 patients in the control group (odds ratio [OR] 0.49, 95% CI 0.40
0.61; p<0.0001). Highly significant differences were seen in both children and
adults, with substantial heterogeneity of the intervention effect across the 10
sites (I(2)=84%, 95% CI 66-96). 140 patients in the C-reactive protein group and
137 patients in the routine care group missed the urine test on day 3, 4, or 5.
Antibiotic activity in urine on day 3, 4, or 5 was found in 267 (30%) of 877
patients in the C-reactive protein group versus 314 (36%) of 882 patients in the
routine treatment group (OR 0.78, 95% CI 0.63-0.95; p=0.015). Time to resolution
of symptoms was similar in both groups. Adverse events were rare, with no deaths
and a total of 14 hospital admissions (six in the C-reactive protein group and
eight in the control group). INTERPRETATION: C-reactive protein point-of-care
testing reduced antibiotic use for non-severe acute respiratory tract infection
without compromising patients' recovery in primary health care in Vietnam. Health
care providers might have become familiar with the clinical picture of low C
reactive protein, leading to reduction in antibiotic prescribing in both groups,
but this would have led to a reduction in observed effect, rather than
overestimation. Qualitative analysis is needed to address differences in context
in order to implement this strategy to improve rational antibiotic use for
patients with acute respiratory infection in low-income and middle-income
countries. FUNDING: Wellcome Trust, UK, and Global Antibiotic Resistance
Partnership, USA.
PMID- 27495140
TI - Posttransplantation cyclophosphamide and sirolimus for prevention of GVHD after
HLA-matched PBSC transplantation.
PMID- 27495141
TI - RNASwift: A rapid, versatile RNA extraction method free from phenol and
chloroform.
AB - RNASwift is an inexpensive, versatile method for the rapid extraction of RNA.
Existing RNA extraction methods typically use hazardous chemicals including
phenol, chloroform and formamide which are often difficult to completely remove
from the extracted RNA. RNASwift uses sodium chloride and sodium dodecyl sulphate
to lyse the cells and isolate the RNA from the abundant cellular components in
conjunction with solid phase extraction or isopropanol precipitation to rapidly
purify the RNA. Moreover, the purified RNA is directly compatible with downstream
analysis. Using spectrophotometry in conjunction with ion pair reverse phase
chromatography to analyse the extracted RNA, we show that RNASwift extracts and
purifies RNA of higher quality and purity in comparison to alternative RNA
extraction methods. The RNASwift method yields approximately 25 MUg of RNA from
only 10(8)Escherichia coli cells. Furthermore, RNASwift is versatile; the same
simple reagents can be used to rapidly extract RNA from a variety of different
cells including bacterial, yeast and mammalian cells. In addition to the
extraction of total RNA, the RNASwift method can also be used to extract double
stranded RNA from genetically modified E. coli in higher yields compared to
alternative methods.
PMID- 27495142
TI - Rapid agarose gel electrophoretic mobility shift assay for quantitating protein:
RNA interactions.
AB - Interactions between proteins and nucleic acids are frequently analyzed using
electrophoretic mobility shift assays (EMSAs). This technique separates bound
protein:nucleic acid complexes from free nucleic acids by electrophoresis, most
commonly using polyacrylamide gels. The current study utilizes recent advances in
agarose gel electrophoresis technology to develop a new EMSA protocol that is
simpler and faster than traditional polyacrylamide methods. Agarose gels are
normally run at low voltages (~10 V/cm) to minimize heating and gel artifacts. In
this study we demonstrate that EMSAs performed using agarose gels can be run at
high voltages (>=20 V/cm) with 0.5 * TB (Tris-borate) buffer, allowing for short
run times while simultaneously yielding high band resolution. Several parameters
affecting band and image quality were optimized for the procedure, including gel
thickness, agarose percentage, and applied voltage. Association of the siRNA
binding protein p19 with its target RNA was investigated using the new system.
The agarose gel and conventional polyacrylamide gel methods generated similar
apparent binding constants in side-by-side experiments. A particular advantage of
the new approach described here is that the short run times (5-10 min) reduce
opportunities for dissociation of bound complexes, an important concern in non
equilibrium nucleic acid binding experiments.
PMID- 27495143
TI - Comorbidities, treatment, and outcome in severe anogenital inverse acne
(hidradenitis suppurativa): a 15-year single center report.
AB - BACKGROUND: Acne inversa (hidradentitis suppurativa; AI) is a severe chronic
relapsing inflammatory skin disease of unknown cause. Anogenital AI has the
strongest negative impact on quality of life and causes great disability.
OBJECTIVES: We analyzed patients, comorbities, outcome of extensive surgery, and
possible adverse effects. PATIENTS AND METHODS: We included patients from January
2000 to March 2015 with anogenital AI Hurley grade III. They were further
characterized by modified Sartorius scale, gender and age, comorbidities,
pretreatments, and type of surgery (open or closed), and complications. Pain was
measured by visual analogue scale (VAS). Treatment was performed by wide excision
surgery. RESULTS: A total of 117 patients were identified; mean age was 40.6 +/-
12.6 years. The mean modified Sartorius score was 30.4 +/- 8.4. Risk factors of
obesity and active smoking were seen in 31.6% and 14.5%, respectively. Colostomy
was needed in a single patient only. Pain was reduced significantly. Intra- and
postoperative complications were seen in 20.5% (24/117). CONCLUSIONS: Anogenital
AI is a severe and potentially life threatening disease. Severe anogenital AI can
be effectively treated by aggressive surgery. Outcome depends also on
comorbidities.
PMID- 27495144
TI - In vivo imaging of cancer cell size and cellularity using temporal diffusion
spectroscopy.
AB - PURPOSE: A temporal diffusion MRI spectroscopy based approach has been developed
to quantify cancer cell size and density in vivo. METHODS: A novel imaging
microstructural parameters using limited spectrally edited diffusion (IMPULSED)
method selects a specific limited diffusion spectral window for an accurate
quantification of cell sizes ranging from 10 to 20 MUm in common solid tumors. In
practice, it is achieved by a combination of a single long diffusion time pulsed
gradient spin echo (PGSE) and three low-frequency oscillating gradient spin echo
(OGSE) acquisitions. To validate our approach, hematoxylin and eosin staining and
immunostaining of cell membranes, in concert with whole slide imaging, were used
to visualize nuclei and cell boundaries, and hence, enabled accurate estimates of
cell size and cellularity. RESULTS: Based on a two compartment model
(incorporating intra- and extracellular spaces), accurate estimates of cell sizes
were obtained in vivo for three types of human colon cancers. The IMPULSED
derived apparent cellularities showed a stronger correlation (r = 0.81; P <
0.0001) with histology-derived cellularities than conventional ADCs (r = -0.69; P
< 0.03). CONCLUSION: The IMPULSED approach samples a specific region of temporal
diffusion spectra with enhanced sensitivity to length scales of 10-20 MUm, and
enables measurements of cell sizes and cellularities in solid tumors in vivo.
Magn Reson Med 78:156-164, 2017. (c) 2016 International Society for Magnetic
Resonance in Medicine.
PMID- 27495145
TI - Immune modulation by hypofractionated stereotactic radiation therapy: Therapeutic
implications.
AB - Stereotactic body radiation therapy (SBRT) has become an attractive treatment
modality and a safe, non-invasive alternative to surgery to control primary or
secondary malignant tumors. While emphasis has been on the local tumor control as
a treatment objective for SBRT, the rare but intriguing observations of abscopal
(or out-of-field) effects have pointed to the exciting possibility of activating
anti-tumor immunity by using high-dose radiation. This review summarizes the
available evidence supporting immune modulation by SBRT alone, as well as its
potential combination with immunotherapy. Promising preclinical research has
revealed an array of immune changes following SBRT, which could affect the
balance between anti-tumor immunity and tumor-promoting immunosuppression.
However, shifting this balance in the clinical setting to obtain survival
benefits has rarely been achieved so far, emphasizing the need for a better
understanding of the interactions between high-dose radiotherapy and immunity or
immunotherapy. Nevertheless, the combination of SBRT with immunotherapy,
particularly with immune checkpoint blockers, has the clear potential to
substantially increase the rate of abscopal effects. This warrants further
research in this area, both in mechanistic preclinical studies and in clinical
trials incorporating correlative studies.
PMID- 27495146
TI - Evaluating the utility of provider-recorded clinical status in the medical
records of HIV-positive adults in a limited-resource setting.
AB - Provider-reported summaries of clinical status may assist with clinical
management of HIV in resource poor settings if they reflect underlying biological
processes associated with HIV disease progression. However, their ability to do
so is rarely evaluated. Therefore, we aimed to assess the relationship between a
provider-recorded summary of clinical status and indicators of HIV progression.
Data were abstracted from 201 randomly selected medical records at a large HIV
clinic in the Dominican Republic. Multivariable logistic regressions were used to
examine the relationship between provider-assigned clinical status and
demographic (gender, age, nationality, education) and clinical factors (reported
medication adherence, CD4 cell count, viral load). The mean age of patients was
41.2 (SD = +/-10.9) years and most were female (n = 115, 57%). None of the
examined characteristics were significantly associated with provider-recorded
clinical status. Higher CD4 cell counts were more likely for females (OR = 2.2
CI: 1.12-4.31) and less likely for those with higher viral loads (OR = 0.33 CI:
0.15-0.72). Poorer adherence and lower CD4 cell counts were significantly
associated with higher viral loads (OR = 4.46 CI: 1.11-20.29 and 6.84 CI: 1.47
37.23, respectively). Clinics using provider-reported summaries of clinical
status should evaluate the performance of these assessments to ensure they are
associated with biologic indicators of disease progression.
PMID- 27495147
TI - Factors associated with non-retention in HIV care in an era of widespread
antiretroviral therapy.
AB - In an era of antiretroviral therapy (ART) for all HIV-1-infected patients, our
primary aim was to describe prevalence and characteristics of patients disengaged
from care at an urban ambulatory HIV clinic. We conducted a nested case-control
study. All patients who disengaged from care (defined as being lost to follow-up
for at least one year) from 2007 to 2014 inclusive were identified. Cases were
matched to controls in a 1:4 ratio. A total of 1250 cases were included; 250/2289
(10.9%) of patients attending our HIV clinic disengaged from 2007 to 2014. One
hundred and twenty-six (50.4%) were heterosexual, 81 (32.4%) were men who have
sex with men and 40 (16%) were intravenous drug users. On univariate analysis
only, patients with heterosexual risk were more likely to disengage from care
(50.4% vs. 33.7%, p: <0.001). Those who disengaged were younger, mean age of 39
(p: <0.001). A higher proportion of patients who disengaged from care was not
receiving ART and did not have a suppressed HIV-1 viral load (p: <0.001). On
multivariable analysis, Irish patients were less likely to disengage from HIV
care (odds ratio: 0.567, p: 0.002). Factors associated with non-retention in HIV
care have been identified. A semi-structured interview of those patients who re
engaged will take place to further examine reasons for disengagement from care.
PMID- 27495148
TI - Improving childhood nutrition and wellness in South Africa: involving
mothers/caregivers of malnourished or HIV positive children and health care
workers as co-designers to enhance a local quality improvement intervention.
AB - BACKGROUND: A significant proportion of children admitted to a hospital in a
South African sub-district in 2010 were severely malnourished and - when
concurrently HIV positive - were not correctly initiated on antiretroviral
therapy. Audit data over a subsequent four year period revealed that 60 % of
malnourished children admitted to the hospital were HIV positive. To supplement
an ongoing local quality improvement (QI) intervention addressing poor
nutritional outcomes in children in this setting, Experience-based Co-design
(EBCD) was used to enhance previously low levels of mother, carer and staff
engagement. METHODS: EBCD was implemented over an 8 month period. Non-participant
observation was conducted comprising a total of 10 h in 5 different clinical
locations. Semi-structured interviews were undertaken with 14 purposively
selected staff members as well as 10 mothers/caregivers. The staff interviews
were audio-taped whilst the mothers/caregiver interviews were filmed; both sets
of experiences were analysed for key 'touchpoints'. Mothers/caregivers and staff
participated in separate feedback events and then came together to identify their
shared priorities for improving the service. Participants worked together in 3
smaller co-design teams to implement improvements. RESULTS: There was overlap in
staff and mother/carer views as to their priorities for QI. However, whilst staff
typically highlighted pragmatic issues, mothers/caregivers were more likely to
identify experiential and relational issues. A total of 38 QI interventions were
proposed after the priorities had been discussed and delegated to the 3 co-design
teams; 25 of these changes had been implemented or were being planned for by the
end of the study period. Examples included: a point of care blood machine being
bought to shorten the time in the emergency department whilst waiting for
laboratory results; a play area being organised for children attending the HIV
clinic; the development of three standard operating procedures to improve
clinical handover and waiting times; and privacy screens installed to improve
privacy in reception. CONCLUSIONS: The impact of EBCD was noted both in practical
improvements focused on a better experience for mothers/caregivers and children
within the system and in reflections from stakeholders as to the value added to
the ongoing QI intervention by the co-design process.
PMID- 27495149
TI - Using multivariate cross correlations, Granger causality and graphical models to
quantify spatiotemporal synchronization and causality between pest populations.
AB - BACKGROUND: This work combines multivariate time series analysis and graph theory
to detect synchronization and causality among certain ecological variables and to
represent significant correlations via network projections. Four different
statistical tools (cross-correlations, partial cross-correlations, Granger
causality and partial Granger causality) utilized to quantify correlation
strength and causality among biological entities. These indices correspond to
different ways to estimate the relationships between different variables and to
construct ecological networks using the variables as nodes and the indices as
edges. Specifically, correlations and Granger causality indices introduce rules
that define the associations (links) between the ecological variables (nodes).
This approach is used for the first time to analyze time series of moth
populations as well as temperature and relative humidity in order to detect
spatiotemporal synchronization over an agricultural study area and to illustrate
significant correlations and causality interactions via graphical models.
RESULTS: The networks resulting from the different approaches are trimmed and
show how the network configurations are affected by each construction technique.
The Granger statistical rules provide a simple test to determine whether one
series (population) is caused by another series (i.e. environmental variable or
other population) even when they are not correlated. In most cases, the
statistical analysis and the related graphical models, revealed intra-specific
links, a fact that may be linked to similarities in pest population life cycles
and synchronizations. Graph theoretic landscape projections reveal that
significant associations in the populations are not subject to landscape
characteristics. Populations may be linked over great distances through physical
features such as rivers and not only at adjacent locations in which significant
interactions are more likely to appear. In some cases, incidental connections,
with no ecological explanation, were also observed; however, this was expected
because some of the statistical methods used to define non trivial associations
show connections that cannot be interpreted phenomenologically. CONCLUSIONS:
Incorporating multivariate causal interactions in a probabilistic sense comes
closer to reality than doing per se binary theoretic constructs because the
former conceptually incorporate the dynamics of all kinds of ecological variables
within the network. The advantage of Granger rules over correlations is that
Granger rules have dynamic features and provide an easy way to examine the
dynamic causal relations of multiple time-series variables. The constructed
networks may provide an intuitive, advantageous representation of multiple
populations' associations that can be realized within an agro-ecosystem. These
relationships may be due to life cycle synchronizations, exposure to a shared
climate or even more complicated ecological interactions such as moving behavior,
dispersal patterns and host allocation. Moreover, they are useful for drawing
inferences regarding pest population dynamics and their spatial management.
Extending these models by including more variables should allow the exploration
of intra and interspecies relationships in larger ecological systems, and the
identification of specific population traits that might constrain their
structures in larger areas.
PMID- 27495150
TI - Robot-assisted laparoscopic pyeloplasty for ureteropelvic junction obstruction:
comparison between pediatric and adult patients-Japanese series.
AB - Robotic-assisted procedures are gaining traction as a viable form of minimally
invasive surgery in the field of reconstructive surgery. In this article, the aim
is to present our initial experience and clinical outcomes of robot-assisted
laparoscopic pyeloplasty (RAL-P). We performed RAL-P in 22 patients for the
management of ureteropelvic junction obstruction between December 2012 and August
2015. The da Vinci(r) S surgical system was utilized for all cases. All
procedures were performed via a transperitoneal approach. We assessed
perioperative outcomes, and furthermore, compared between pediatric and adult
patients undergoing this procedure. Dismembered procedures were performed in 19
patients. Three patients underwent Y-V plasty, and two patients who experienced
failure during the primary pyeloplasty had to undergo reoperation. Although the
console time for pediatric patients was significantly shorter than that of adults
(123.1 +/- 18.3, 162.4 +/- 23.9 min, respectively, p < 0.001), success rate was
not significantly different between pediatric and adults (100 vs 90 %, p =
0.512). According to a comparison of surgical outcomes by age, the console time
was significantly shorter in pediatric than in adult patients. This finding may
be attributable to the differences in intraabdominal fatty tissues. Besides, RAL
P with Y-V plasty was applicable even for cases of failed pyeloplasty. In
conclusion, the surgical outcomes of RAL-P were favorable and safe for both
pediatric and adult patients, and comparable to findings of previous reports. To
our knowledge, this is the first report of a case series of RAL-P in Japan.
PMID- 27495152
TI - Neelika Karunaratne.
PMID- 27495151
TI - Potential health gains and health losses in eleven EU countries attainable
through feasible prevalences of the life-style related risk factors alcohol, BMI,
and smoking: a quantitative health impact assessment.
AB - BACKGROUND: Influencing the life-style risk-factors alcohol, body mass index
(BMI), and smoking is an European Union (EU) wide objective of public health
policy. The population-level health effects of these risk-factors depend on
population specific characteristics and are difficult to quantify without dynamic
population health models. METHODS: For eleven countries-approx. 80 % of the EU-27
population-we used evidence from the publicly available DYNAMO-HIA data-set. For
each country the age- and sex-specific risk-factor prevalence and the incidence,
prevalence, and excess mortality of nine chronic diseases are utilized; including
the corresponding relative risks linking risk-factor exposure causally to disease
incidence and all-cause mortality. Applying the DYNAMO-HIA tool, we dynamically
project the country-wise potential health gains and losses using feasible, i.e.
observed elsewhere, risk-factor prevalence rates as benchmarks. The effects of
the "worst practice", "best practice", and the currently observed risk-factor
prevalence on population health are quantified and expected changes in life
expectancy, morbidity-free life years, disease cases, and cumulative mortality
are reported. RESULTS: Applying the best practice smoking prevalence yields the
largest gains in life expectancy with 0.4 years for males and 0.3 year for
females (approx. 332,950 and 274,200 deaths postponed, respectively) while the
worst practice smoking prevalence also leads to the largest losses with 0.7 years
for males and 0.9 year for females (approx. 609,400 and 710,550 lives lost,
respectively). Comparing morbidity-free life years, the best practice smoking
prevalence shows the highest gains for males with 0.4 years (342,800 less disease
cases), whereas for females the best practice BMI prevalence yields the largest
gains with 0.7 years (1,075,200 less disease cases). CONCLUSION: Smoking is still
the risk-factor with the largest potential health gains. BMI, however, has
comparatively large effects on morbidity. Future research should aim to improve
knowledge of how policies can influence and shape individual and aggregated life
style-related risk-factor behavior.
PMID- 27495153
TI - W44X mutation in the WWOX gene causes intractable seizures and developmental
delay: a case report.
AB - BACKGROUND: WW domain containing oxidoreductase (WWOX) gene was cloned in 2000;
alteration has been seen in many cancer cells. It acts as a tumor suppresser by
blocking cell growth and causing apoptosis. WWOX protein showed different
expression of mice brain and spinal cord, for which deletion causes seizure and
early death. CASE PRESENTATION: Clinical and molecular characteristics of a
consanguineous family show a homozygous mutation of WWOX gene at specific bases,
causing a debilitating syndrome characterized by growth retardation, intractable
epilepsy, intellectual disability, and early death. Using Whole Exome Sequencing
(WES), a novel homozygous mutation in the WWOX gene is identified in a
consanguineous Arab family from Qatar with two daughters who presented with
intractable seizure and developmental delay. CONCLUSION: The study presents the
importance of human WWOX gene for brain development and the association between
gene mutation and epileptic encephalopathy. It also highlights the power of WES
particularly in clinically challenging cases.
PMID- 27495154
TI - Smaller employers are less likely to provide occupational health support.
PMID- 27495155
TI - Hydroxylation of diverse flavonoids by CYP450 BM3 variants: biosynthesis of
eriodictyol from naringenin in whole cells and its biological activities.
AB - BACKGROUND: Cytochrome P450 monooxygenase constitutes a significant group of
oxidative enzymes that can introduce an oxygen atom in a high regio- and stereo
selectivity mode. We used the Bacillus megaterium cytochrome P450 BM3 (CYP450
BM3) and its variants namely mutant 13 (M13) and mutant 15 (M15) for the
hydroxylation of diverse class of flavonoids. RESULTS: Among 20 flavonoids,
maximum seven flavonoids were hydroxylated by the variants while none of these
molecules were accepted by CYP450 BM3 in in vitro reaction. Moreover, M13
exhibited higher conversion of substrates than M15 and CYP450 BM3 enzymes. We
found that M13 carried out regiospecific 3'-hydroxylation reaction of naringenin
with the highest conversion among all the tested flavonoids. The apparent K m and
k cat values of M13 for naringenin were 446 uM and 1.955 s(-1), respectively. In
whole-cell biotransformation experiment with 100 uM of naringenin in M9 minimal
medium with 2 % glucose in shake flask culture, M13 showed 2.14- and 13.96-folds
higher conversion yield in comparison with M15 (16.11 %) and wild type (2.47 %).
The yield of eriodictyol was 46.95 uM [~40.7 mg (13.5 mg/L)] in a 3-L volume lab
scale fermentor at 48 h in the same medium exhibiting approximately 49.81 %
conversion of the substrate. In addition, eriodictyol exhibited higher
antibacterial and anticancer potential than naringenin, flavanone and hesperetin.
CONCLUSIONS: We elucidated that eriodictyol being produced from naringenin using
recombinant CYP450 BM3 and its variants from B. megaterium, which shows an
approach for the production of important hydroxylated compounds of various
polyphenols that may span pharmaceutical industries.
PMID- 27495156
TI - Impact of disease activity and treatment of comorbidities on the risk of
myocardial infarction in rheumatoid arthritis.
AB - BACKGROUND: The aim was to estimate the impact of individual risk factors and
treatment with various disease-modifying antirheumatic drugs (DMARDs) on the
incidence of myocardial infarction (MI) in patients with rheumatoid arthritis
(RA). METHODS: We analysed data from 11,285 patients with RA, enrolled in the
prospective cohort study RABBIT, at the start of biologic (b) or conventional
synthetic (cs) DMARDs. A nested case-control study was conducted, defining
patients with MI during follow-up as cases. Cases were matched 1:1 to control
patients based on age, sex, year of enrolment and five cardiovascular (CV)
comorbidities. Generalized linear models were applied (Poisson regression with a
random component, conditional logistic regression). RESULTS: In total, 112
patients developed an MI during follow-up. At baseline, during the first 6 months
of follow-up and prior to the MI, inflammation markers (erythrocyte sedimentation
rate (ESR) and C-reactive protein (CRP)) but not 28-joint-count disease activity
score (DAS28) were significantly higher in MI cases compared to matched controls
and the remaining cohort. Baseline treatment with DMARDs was similar across all
groups. During follow-up bDMARD treatment was significantly more often
discontinued or switched in MI cases. CV comorbidities were significantly less
often treated in MI cases vs. matched controls (36 % vs. 17 %, p < 0.01). In the
adjusted regression model, we found a strong association between higher CRP and
MI (OR for log-transformed CRP at follow-up: 1.47, 95 % CI 1.00; 2.16).
Furthermore, treatment with prednisone >=10 mg/day (OR 1.93, 95 % CI 0.57; 5.85),
TNF inhibitors (OR 0.91, 95 % CI 0.40; 2.10) or other bDMARDs (OR 0.85, 95 % CI
0.27; 2.72) was not associated with higher MI risk. CONCLUSIONS: CRP was
associated with risk of MI. Our results underline the importance of tight disease
control taking not only global disease activity, but also CRP as an individual
marker into account. It seems irrelevant with which class of (biologic or
conventional) DMARD effective control of disease activity is achieved. However,
in some patients the available treatment options were insufficient or
insufficiently used - regarding DMARDs to treat RA as well as regarding the
treatment of CV comorbidities.
PMID- 27495157
TI - Circadian variation of the pancreatic islet transcriptome.
AB - Pancreatic islet failure is a characteristic feature of impaired glucose control
in diabetes mellitus. Circadian control of islet function is essential for
maintaining proper glucose homeostasis. Circadian variations in transcriptional
pathways have been described in diverse cell types and shown to be critical for
optimization of cellular function in vivo. In the current study, we utilized
Short Time Series Expression Miner (STEM) analysis to identify diurnally
expressed transcripts and biological pathways from mouse islets isolated at 4 h
intervals throughout the 24 h light-dark cycle. STEM analysis identified 19
distinct chronological model profiles, and genes belonging to each profile were
subsequently annotated to significantly enriched Kyoto Encyclopedia of Genes and
Genomes biological pathways. Several transcriptional pathways essential for
proper islet function (e.g., insulin secretion, oxidative phosphorylation), cell
survival (e.g., insulin signaling, apoptosis) and cell proliferation (DNA
replication, homologous recombination) demonstrated significant time-dependent
variations. Notably, KEGG pathway analysis revealed "protein processing in
endoplasmic reticulum - mmu04141" as one of the most enriched time-dependent
pathways in islets. This study provides unique data set on time-dependent diurnal
profiles of islet gene expression and biological pathways, and suggests that
diurnal variation of the islet transcriptome is an important feature of islet
homeostasis, which should be taken into consideration for optimal experimental
design and interpretation of future islet studies.
PMID- 27495159
TI - When to start renal replacement therapy in critically ill patients with acute
kidney injury: comment on AKIKI and ELAIN.
AB - The dilemma of whether and when to start renal replacement therapy among
critically ill patients with acute kidney injury in the absence of conventional
indications has long been a vexing challenge for clinicians. The lack of high
quality evidence has undoubtedly contributed decisional uncertainty and
unnecessary practice variation. Recently, two randomized trials (ELAIN and AKIKI)
reported specifically on the issue of the timing of initiation of renal
replacement therapy in critically ill patients with acute kidney injury. In this
commentary, their fundamental differences in trial design, sample size, and
widely discrepant findings are considered in context. While both trials are
important contributions towards informing practice on this issue, additional
evidence from large multicenter randomized trials is needed.
PMID- 27495158
TI - RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic
valves by RNA sequencing.
AB - The molecular mechanisms leading to premature development of aortic valve
stenosis (AS) in individuals with a bicuspid aortic valve are unknown. The
objective of this study was to identify genes differentially expressed between
calcified bicuspid aortic valves (BAVc) and tricuspid valves with (TAVc) and
without (TAVn) AS using RNA sequencing (RNA-Seq). We collected 10 human BAVc and
nine TAVc from men who underwent primary aortic valve replacement. Eight TAVn
were obtained from men who underwent heart transplantation. mRNA levels were
measured by RNA-Seq and compared between valve groups. Two genes were
upregulated, and none were downregulated in BAVc compared with TAVc, suggesting a
similar gene expression response to AS in individuals with bicuspid and tricuspid
valves. There were 462 genes upregulated and 282 downregulated in BAVc compared
with TAVn. In TAVc compared with TAVn, 329 genes were up- and 170 were
downregulated. A total of 273 upregulated and 147 downregulated genes were
concordantly altered between BAVc vs. TAVn and TAVc vs. TAVn, which represent 56
and 84% of significant genes in the first and second comparisons, respectively.
This indicates that extra genes and pathways were altered in BAVc. Shared
pathways between calcified (BAVc and TAVc) and normal (TAVn) aortic valves were
also more extensively altered in BAVc. The top pathway enriched for genes
differentially expressed in calcified compared with normal valves was fibrosis,
which support the remodeling process as a therapeutic target. These findings are
relevant to understand the molecular basis of AS in patients with bicuspid and
tricuspid valves.
PMID- 27495160
TI - 'How families live ...' - the views and experiences of parent-carers who provide
family placements to intellectual disability nursing students.
AB - AIM: We aimed to learn about the value of family placements from the perspective
of parent-carers who provide them to nurse students via a Scottish university
Family Placement Scheme. METHOD: Qualitative interviews were conducted with seven
parent-carers who provided a family placement over two academic years.
Descriptive data was analysed, organized into themes and subject to content
analysis: parents' descriptions of caring; their perceived value of family
placements; and their views and experiences of participation in intellectual
disability nurse education. RESULTS: Family placements are beneficial to nurse
students and families with children with an intellectual disability. Description
of wider aspects of caring was provided, offering insight into learning
experiences of students on placement. CONCLUSION: This model of learning provides
opportunities for students to appreciate the reality of caring for a relative
with an intellectual disability at home. Students develop their practice skills
for working in partnership with family carers.
PMID- 27495161
TI - Nitric Oxide Upregulates Proteasomal Protein Degradation in Neurons.
AB - Nitric oxide (NO) is involved in many neuronal functions such as neuromodulation
and intracellular signaling. Recent studies have demonstrated that nitric oxide
is involved in regulation of proteasomal protein degradation. However, its role
in neuronal protein degradation still remains unclear. In our study, we
investigated the influence of endogenous nitric oxide production in this process.
We have shown that nitric oxide synthase blockade prevents decline of the UbG76V
GFP fluorescence (GFP-based proteasomal protein degradation reporter) in neuronal
processes of the cultured hippocampal neurons. It suggests that nitric oxide may
regulate ubiquitin-dependent proteasomal protein degradation in neurons. Also, we
have confirmed that the NO synthesis blockade alone significantly impairs long
term potentiation, and demonstrated for the first time that simultaneous blockade
of the NO and proteins synthesis leads to the long-term potentiation amplitude
rescue to the control values. Obtained results suggest that nitric oxide is
involved in the protein degradation in proteasomes in physiological conditions.
PMID- 27495162
TI - Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the
Design of Drugs for Rare Diseases.
AB - The study provides the physicochemical characteristic of bosentan (BOS) in
comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports
dealing with thermal characteristic of SIL and TA, physicochemical properties of
BOS have not been investigated so far. Recent clinical reports have indicated
that the combination of bosentan and PDE-5 inhibitor can improve the
effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH).
However, in order to design personalized medicines for therapy of chronic rare
diseases, detailed information on the thermal behaviour and solubility of each
drug is indispensable. Thus, XRD, DSC and TGA-QMS analyses were applied to
compare the properties of the drugs, their thermal stability as well as to
identify the products of thermal degradation. The dehydration of BOS started at
70 degrees C and was followed by the chemical degradation with the onset at 290
degrees C. The highest thermal stability was stated for TA, which decomposed at
ca. 320 degrees C, whereas the lowest onset of the thermal decomposition process
was stated for SIL, i.e. 190 degrees C. The products of the drug decomposition
were identified. FT-FIR was applied to study intra- and intermolecular
interactions between the drug molecules. FT-MIR and Raman spectroscopy were used
to examine the chemical structure of the drugs. Chemoinformatic tools were used
to predict the polar surface area, pKa, or logP of the drugs. Their results were
in line with solubility and dissolution studies.
PMID- 27495163
TI - Rapid Analysis of the Quality of Amoxicillin and Clavulanate Potassium Tablets
Using Diffuse Reflectance Near-Infrared Spectroscopy.
AB - The cycle-closed dimer of amoxicillin influences its critical quality and is an
important impurity in amoxicillin and clavulanate potassium tablets. The quality
of the tablets could be rapidly evaluated using the impurity as an indicator.
Here, we report a quantitative model to determine the cycle-closed dimer in
samples from different manufacturers using diffuse reflectance near-infrared
(NIR) spectroscopy by partial least squares regression for one y variable (PLS1)
and hierarchical cluster analysis. Because the contents of the (active
pharmaceutical ingredients) APIs (amoxicillin and clavulanate potassium) and
water are also the important indexes of the tablet quality, three other
quantitative models were used to confirm the API data and water content. All of
the four models facilitate rapid and complete control of the tablet quality. In
addition, quantitative models were validated in terms of specificity, linearity,
accuracy, repeatability, and intermediate precision according to the
International Conference on Harmonisation guidelines by evaluating the
characteristics of the NIR spectra. These results confirmed that the models were
satisfactory.
PMID- 27495164
TI - [Do we need to relearn abdominal wall closure? : Small stitches].
AB - The 1-year incisional hernia rate of 9-30 % has been tolerated for decades. Even
in the 1970s and 1980s there was evidence that supported reducing suture tension.
Recently, the traditional 4:1 relationship between suture and wound length, which
has been passed on for years, has been questioned. After first experimental and
clinical data suggested an advantage by reducing the width and interval of
stitches by 50 %, the prospective randomized STITCH study has now provided
evidence by significantly lowering the 1-year hernia rate from 21 % to 13 %. For
surgeons this means less of a revolution and more of an innovative evolution of a
long-established technique. Before introduction of the technique quality
assurance must be carried out with documentation of performance indicators (e.g.
number of stitches, length of thread incorporated and wound length).
PMID- 27495165
TI - [Surgical anatomy of the abdominal wall].
AB - Knowledge of the anterolateral abdominal wall anatomy is crucial for a surgical
approach to the abdominal cavity and for reconstructive surgery of abdominal wall
defects. Furthermore it can help the surgeon ensure optimal surgical results by
avoiding anatomical complications. This overview presents the surgical relevant
anatomy and emphasizes surgical principles and pitfalls in abdominal wall
surgery.
PMID- 27495166
TI - Health-related quality of life and associated factors in people with HIV: an
Irish cohort study.
AB - BACKGROUND: Considering the chronic and debilitating nature of HIV infection,
health-related quality of life (HRQoL) is an important patient-reported clinical
outcome to better understand the effects of this infection and its treatment on
patients' lives. The purpose of this study was to assess the HRQoL and its
association with sociodemographic, behavioural, clinical, nutrition-related
factors and social support in an Irish HIV cohort. METHODS: A cross-sectional,
prospective study using the Medical Outcomes Study HIV Health survey assessed the
10 dimensions of HRQoL and summarised as Physical Health Summary (PHS) and Mental
Health Summary (MHS) scores. Participants were categorised as having good or poor
PHS and MHS using the standardised mean score of 50. The variables independently
associated with PHS and MHS were identified using multivariable logistic
regression models. RESULTS: Overall, 521 participants completed the HRQoL
questionnaire. The median (IQR) PHS and MHS scores were 56 (47-60) and 51 (41-58)
respectively. All the covariate groups had lower MHS than PHS. Participants with
symptoms of HIV reported the lowest median (IQR) PHS score 44.7 (32.-54.5) and
MHS score 36.1 (28.6-48.4). Of the 10 dimensions of HRQoL, the lowest scores were
for the energy level and general health. Symptoms of HIV, co-morbidities, social
support, employment and ethnicity had independent association with both PHS and
MHS. Gender, education, alcohol intake and HIV-complications were associated with
PHS. Age, illicit drugs, BMI and malnutrition were associated with MHS. However,
CD4 count and viral load were not independently associated with PHS and MHS in
multivariable regression models. CONCLUSION: Overall, HIV-infected people in this
cohort had an average level of HRQoL. However, it is impaired in people with
symptoms and co-morbidities, and not independently associated with CD4 and viral
load. Alleviating HIV symptoms and preventing co-morbidities are important in
managing HIV. Providing psychosocial supports for behaviour modification and
return to work or exploring new opportunities will help to improve HRQoL.
Healthcare providers and policy makers need to plan and implement programs to
routinely assess the HRQoL in a systematic method to facilitate a holistic
management of HIV.
PMID- 27495167
TI - Evaluation of the vaginal flora in pregnant women receiving opioid maintenance
therapy: a matched case-control study.
AB - BACKGROUND: Vaginal infections are a risk factor for preterm delivery. In this
study, we sought to evaluate the vaginal flora of pregnant women receiving opioid
maintenance therapy (OMT) in comparison to non-dependent, non-maintained
controls. METHODS: A total of 3763 women with singleton pregnancies who underwent
routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0
gestational weeks were examined. Vaginal smears were Gram-stained, and
microscopically evaluated for bacterial vaginosis, candidiasis, and
trichomoniasis. In a retrospective manner, data of 132 women receiving OMT
(cases) were matched for age, ethnicity, parity, education, previous preterm
delivery, and smoking status to the data of 3631 controls. The vaginal flora at
antenatal screening served as the primary outcome measure. Secondary outcome
measures were gestational age and birth weight. RESULTS: In the OMT group, 62/132
(47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and
31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was
found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 %
CI, 0.33-0.71); p < 0.001]. Candidiasis occurred more frequently in OMT women
than in controls [OR 2.11 (95 % CI, 1.26-3.27); p < 0.001]. Findings were
inconclusive regarding bacterial vaginosis (+/- candidiasis) and trichomoniasis.
Compared to infants of the control group, those of women with OMT had a lower
mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006].
CONCLUSIONS: Pregnant women with OMT are at risk for asymptomatic vaginal
infections. As recurrent candidiasis is associated with preterm delivery, the
vulnerability of this patient population should lead to consequent antenatal
infection screening at early gestation.
PMID- 27495168
TI - Unravelling the effect of the Dutch school-based nutrition programme Taste
Lessons: the role of dose, appreciation and interpersonal communication.
AB - BACKGROUND: To unravel the effect of school-based nutrition education, insight
into the implementation process is needed. In this study, process indicators of
Taste Lessons (a nutrition education programme for Dutch elementary schools) and
their association with changes in behavioural determinants relevant to healthy
eating behaviour are studied. METHODS: The study sample consisted of 392 Dutch
primary school children from 12 schools. Data were collected using teacher and
child questionnaires at baseline, and at one and six months after the
intervention. Multilevel regression analyses were conducted to study the
association between dose, appreciation and children's engagement in interpersonal
communication (talking about Taste Lessons with others after the lessons), and
change in knowledge, awareness, skills, attitude, emotion, subjective norm and
intention towards two target behaviours. RESULTS: With an average implementation
of a third of the programme activities, dose positively predicted change in
children's subjective norm of the teacher after one month. Teachers and children
highly appreciated Taste Lessons. Whereas teacher appreciation was inversely
associated, child appreciation was positively associated with children's change
in awareness, emotion and subjective norm of teachers after one month and in
attitude and subjective norm of parents after six months. Interpersonal
communication was positively associated with children's change in five
determinants after one month and in attitude and intention after six months.
CONCLUSIONS: The implementation process is related to the programme outcomes of
Taste Lessons. Process data provide valuable insights into factors that
contribute to the effect of interventions in real-life settings.
PMID- 27495169
TI - Functional characterization of the Mycobacterium abscessus genome coupled with
condition specific transcriptomics reveals conserved molecular strategies for
host adaptation and persistence.
AB - BACKGROUND: Mycobacterium abscessus subsp. abscessus (MAB) is a highly drug
resistant mycobacterium and the most common respiratory pathogen among the
rapidly growing non-tuberculous mycobacteria. MAB is also one of the most deadly
of the emerging cystic fibrosis (CF) pathogens requiring prolonged treatment with
multiple antibiotics. In addition to its "mycobacterial" virulence genes, the
genome of MAB harbours a large accessory genome, presumably acquired via lateral
gene transfer including homologs shared with the CF pathogens Pseudomonas
aeruginosa and Burkholderia cepacia. While multiple genome sequences are
available there is little functional genomics data available for this important
pathogen. RESULTS: We report here the first multi-omics approach to characterize
the primary transcriptome, coding potential and potential regulatory regions of
the MAB genome utilizing differential RNA sequencing (dRNA-seq), RNA-seq,
Ribosome profiling and LC-MS proteomics. In addition we attempt to address the
genomes contribution to the molecular systems that underlie MAB's adaptation and
persistence in the human host through an examination of MABs transcriptional
response to a number of clinically relevant conditions. These include hypoxia,
exposure to sub-inhibitory concentrations of antibiotics and growth in an
artificial sputum designed to mimic the conditions within the cystic fibrosis
lung. CONCLUSIONS: Our integrated map provides the first comprehensive view of
the primary transcriptome of MAB and evidence for the translation of over one
hundred new short open reading frames (sORFs). Our map will act as a resource for
ongoing functional genomics characterization of MAB and our transcriptome data
from clinically relevant stresses informs our understanding of MAB's adaptation
to life in the CF lung. MAB's adaptation to growth in artificial CF sputum
highlights shared metabolic strategies with other CF pathogens including P.
aeruginosa and mirrors the transcriptional responses that lead to persistence in
mycobacteria. These strategies include an increased reliance on amino acid
metabolism, and fatty acid catabolism and highlights the relevance of the
glyoxylate shunt to growth in the CF lung. Our data suggests that, similar to
what is seen in chronically persisting P. aeruginosa, progression towards a
biofilm mode of growth would play a more prominent role in a longer-term MAB
infection. Finally, MAB's transcriptional response to antibiotics highlights the
role of antibiotic modifications enzymes, active transport and the evolutionarily
conserved WhiB7 driven antibiotic resistance regulon.
PMID- 27495170
TI - Smooth muscle cell sheet transplantation preserve cardiac function and minimize
cardiac remodeling in a rat myocardial infarction model.
AB - BACKGROUND: We examined whether a vascular smooth muscle cell (SMC) sheet is
effective in the treatment of a rat myocardial infarction (MI) model. METHODS: We
examined the effect of SMC sheet on the cardiac function and cardiac remodeling
in a rat MI model in comparison with their effect of dermal fibroblast (DFB)
sheet in vivo. Furthermore, we estimated the apoptosis and secretion of
angiogenic factor of SMC under hypoxic condition in comparison with DFB. Seven
days after MI, monolayer cell sheets were transplanted on the infarcted area (SMC
transplantation group, SMC-Tx; DFB transplantation group, DFB-Tx; no cell sheet
transplantation group, Untreated; neither MI nor cell sheet transplantation
group, Sham). We evaluated cardiac function by echocardiogram, degree of cardiac
remodeling by histological examination, and secretion of angiogenic growth factor
by enzyme immunoassay. RESULTS: Twenty-eight days after transplantation, SMC-Tx
showed the following characteristics compared with the other groups: 1)
significantly greater fractional area shortening (SMC-Tx, 32.3 +/- 2.1 %; DFB-Tx,
23.3 +/- 2.1 %; untreated, 25.1 +/- 2.6 %), 2) suppressed left ventricular
dilation, smaller scar expansion, and preserved wall thickness of the area at
risk and the posterior wall, 3) decreased fibrosis, preserved myocardium in the
scar area, and greater number of arterioles in border-zone, 4) tight attachment
of SMC sheets on the scarred myocardium, and less apoptotic cell death. In in
vitro experiments, SMCs secreted higher amounts of basic fibroblast growth factor
(SMC, 157.7 +/- 6.4 pg/ml; DFB, 3.1 +/- 1.0 pg/ml), and showed less apoptotic
cell death under hypoxia. CONCLUSIONS: Our results illustrate that
transplantation of SMC sheets inhibited the progression of cardiac remodeling and
improve cardiac function. These beneficial effects may be due to superior SMC
survival.
PMID- 27495171
TI - Patient-Centered Outcome Measures to Assess Functioning in Randomized Controlled
Trials of Low-Vision Rehabilitation: A Review.
AB - Low-vision rehabilitation (LVR) aims to improve the functioning of patients with
chronic uncorrectable visual impairment. LVR is inherently a patient-centered
intervention since its approach and goals are dictated by the needs and abilities
of each individual patient. Accordingly, it is essential to have patient-centered
outcome (PCO) measures to assess and compare the efficacy and effectiveness of
low-vision interventions; however, there is a lack of evidence on the
effectiveness of LVR interventions. We reviewed the literature in order to
identify randomized controlled trials (RCTs) in the field of LVR and the outcome
measures used to assess patient functioning in these trials. We identified 15
RCTs of LVR that employed nine unique patient-reported, five unique performance
based, and one hybrid (combined patient-reported and performance) outcome
measures. Since these trials used distinct tools to assess patient functioning,
it is difficult to compare the effectiveness of competing rehabilitation
interventions across studies. Selecting valid outcome measures that are both
relevant to LVR goals of specific patient populations and that measure
functioning across a range of visually demanding tasks could improve the ability
to detect the effect of LVR and to compare rehabilitation strategies. There are
advantages and limitations to the use of both patient-reported and performance
based outcome measures, and additional work should be undertaken to explore the
relationship between these modes of assessment, as well as strategies for
optimally integrating these approaches. Careful selection of outcome measures in
the design of future RCTs in LVR may lead to improved understanding of the
effectiveness of LVR and, ultimately, to improved functioning of patients with
low vision.
PMID- 27495172
TI - Inhibition of mouse breast adenocarcinoma growth by ablation with intratumoral
alpha-irradiation combined with inhibitors of immunosuppression and CpG.
AB - It has been demonstrated that aggressive in situ tumor destruction (ablation)
could lead to the release of tumor antigens, which can stimulate anti-tumor
immune responses. We developed an innovative method of tumor ablation based on
intratumoral alpha-irradiation, diffusing alpha-emitters radiation therapy
(DaRT), which efficiently ablates local tumors and enhances anti-tumor immunity.
In this study, we investigated the anti-tumor potency of a treatment strategy,
which combines DaRT tumor ablation with two approaches for the enhancement of
anti-tumor reactivity: (1) neutralization of immunosuppressive cells such as
regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and (2)
boost the immune response by the immunoadjuvant CpG. Mice bearing DA3 mammary
adenocarcinoma with metastases were treated with DaRT wires in combination with a
MDSC inhibitor (sildenafil), Treg inhibitor (cyclophosphamide at low dose), and
the immunostimulant, CpG. Combination of all four therapies led to a complete
rejection of primary tumors (in 3 out of 20 tumor-bearing mice) and to the
elimination of lung metastases. The treatment with DaRT and Treg or MDSC
inhibitors (without CpG) also resulted in a significant reduction in tumor size,
reduced the lung metastatic burden, and extended survival compared to the
corresponding controls. We suggest that the therapy with DaRT combined with the
inhibition of immunosuppressive cells and CpG reinforced both local and systemic
anti-tumor immune responses and displayed a significant anti-tumor effect in
tumor-bearing mice.
PMID- 27495173
TI - Orbital myiasis in eviscerated socket and review of literature.
AB - Orbital myiasis is a potentially destructive infestation of the orbital tissues.
It is uncommon in clinical practice and is seen in patients with poor hygiene
with debilitated or immunocompromised state. We report a case of orbital myiasis
in an empty socket of an immunocompetent individual. A 65-year-old
immunocompetent patient was found to have orbital myiasis in an empty socket
status postevisceration, for which he underwent treatment by manual removal of
the larvae after application of a suffocating agent, turpentine oil. A total of
12 larvae were removed over the ensuing week. The tissues healed with secondary
intention leaving an irregular healthy scar. It was noteworthy that once
eviscerated the eye was neglected by the patient. Empty orbital sockets are
potential sites for infestations.
PMID- 27495174
TI - Non-invasive ventilation for sleep-disordered breathing in Smith-Magenis
syndrome.
AB - Smith-Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder
characterised by behavioural disturbances, intellectual disability and early
onset obesity. The physical features of this syndrome are well characterised;
however, behavioural features, such as sleep disturbance, are less well
understood and difficult to manage. Sleep issues in SMS are likely due to a
combination of disturbed melatonin cycle, facial anatomy and obesity-related
ventilatory problems. Sleep disorders can be very distressing to patients and
their families, as exemplified by our patient's experience, and can worsen
behavioural issues as well as general health. This case demonstrates the
successful use of non-invasive ventilation in treating underlying obesity
hypoventilation syndrome and obstructive sleep apnoea. As a consequence of
addressing abnormalities in sleep patterns, some behavioural problems improved.
PMID- 27495175
TI - Cor triatriatum sinister with severe obstruction: a rare presentation in an
adult.
AB - Cor triatriatum sinister is a rare congenital anomaly usually presenting in
infancy or childhood. Most cases reported in adulthood have minimal obstruction.
A case of critically obstructed cor triatriatum sinister presenting for the first
time in adulthood is described here. The characteristic ECG, radiological and
echocardiographic findings of this rare anomaly are demonstrated in this case
report. The clinical features closely mimic mitral stenosis. The clues to
differentiate cor triatriatum from other causes of left ventricular inflow
obstruction are described.
PMID- 27495176
TI - Transanal endoscopic microsurgery in the management of rectal wall endometriosis.
AB - A 29-year-old woman with known history of endometriosis was referred to
colorectal outpatient clinic from gynaecology with a history of intermittent
rectal bleeding and no associated bowel symptoms. Flexible sigmoidoscopy in
concordance with pelvic MRI revealed a 3*2*2 cm sessile lesion in the anterior
rectal wall. The lesion was also palpable as a firm mass on digital rectal
examination. From the gynaecological point of view no intra-abdominal exploration
was required; the sole rectal wall lesion was removed with the minimally invasive
surgical technique of transanal endoscopic microsurgery. Full thickness rectal
wall excision sample was reported to be histologically complete and confirmed
endometriosis. No recurrence was detected at endoscopic follow-up at 6 months.
The patient remained symptom free. Therefore, we demonstrated a case of minimally
invasive removal of a rectal wall large endometriosis nodule in a fertile woman
with a complete, symptomatic, uneventful recovery.
PMID- 27495177
TI - Re-emergent tremor in a patient with Parkinson's disease.
PMID- 27495178
TI - Systemic sarcoidosis with hypercalcaemia, hypothalamic-pituitary dysfunction and
thyroid involvement.
AB - Sarcoidosis is a multisystem granulomatous disorder. The lungs are the principal
organs affected, however, extrapulmonary involvement including disorders of the
pituitary and thyroid glands has been reported but presentation with multiple
endocrine manifestations is rare. We report the case of a 36-year-old African
American woman who presented with hypercalcaemia, abnormal thyroid function
studies and secondary amenorrhoea. On workup including laboratory, radiological
testing and biopsy she was diagnosed with sarcoidosis with multi-organ
involvement. Endocrine manifestations included non-parathyroid hormone mediated
hypercalcaemia related to sarcoidosis, thyroid involvement with sarcoidosis and
hypothalamic-pituitary involvement with a sellar and suprasellar mass associated
with secondary adrenal insufficiency, secondary hypogonadism, growth hormone
deficiency and secondary hypothyroidism. We report to the best of our knowledge
the first case of simultaneous multiple endocrine manifestations of sarcoidosis
that included hypercalcaemia, hypopituitarism and sarcoidosis of the thyroid
gland.
PMID- 27495179
TI - The starch-bound alpha-amylase/trypsin-inhibitors in Avena.
AB - Oat kernels exhibit an extra-soft texture, a trait recently demonstrated to be
largely modulated by starch-bound tryptophan-rich 2S proteins, the vromindolines.
In this study, fractionation by two-dimensional electrophoresis of starch-bound
proteins in 25 oat (Avena sativa) cultivars and 11 diploid or tetraploid Avena
species revealed novel 2S proteins called Avena alpha-amylase/trypsin-inhibitors
(AATI) because of their sequence similarity with wheat alpha-amylase/trypsin
inhibitors. Thirty-seven AATI polypeptides, about 14 kDa in size, were split into
three families named AATI-1, AATI-2, and AATI-3 with different primary structures
and isoelectric points. AATI-1 and AATI-2 proteins showed 55.5-60.0 % sequence
similarity with wheat alpha-amylase inhibitors CM1, CM2, and CM16, which have
been found to cause innate immunity responses in celiac disease and non-celiac
gluten sensitivity. Diploid A-genome and tetraploid AC-genome oat species possess
three and five genes encoding for the AATI proteins, respectively, whereas
hexaploid A. sativa exhibits 12 genes dispersed over the A-, C-, and D-genomes.
Some AATI proteins expressed in hexaploid oats were assigned to the A-genome
based on similarity to their counterparts in diploid species, contributing to
further clarify the genetic origin of hexaploid oats. Moreover, AATI may interact
with starch-bound vromindolines in determining the extra-soft texture of oat
kernels and, due to their balanced amino acid compositions, may contribute to the
biological value of oat proteins in a positive manner.
PMID- 27495181
TI - Male-specific risk of first and recurrent venous thrombosis: a phylogenetic
analysis of the Y chromosome.
AB - : Essentials Men have an unexplained higher risk of a first and recurrent venous
thrombosis (VT) than women. We studied the role of the major European Y
chromosome haplogroups in first and recurrent VT. In contrast to a study on
coronary artery disease, haplogroup I was not linked to VT risk. Haplogroup E
carriers may have an increased risk of recurrent VT, but a larger study is
needed. SUMMARY: Background The risk of venous thrombosis (VT) recurrence is
higher in men than in women. When reproductive risk factors are excluded, this
sex difference is also apparent for a first VT. The current explanations for this
difference are insufficient. Objectives To study the association between
chromosome Y haplogroups and the risks of a first and recurrent VT. Methods Y
chromosomes of 3742 men (1729 patients; 2013 controls) from the MEGA case-control
study were tracked into haplogroups according to the phylogenetic tree. We
calculated the risk of a first VT by comparing the major haplogroups with the
most frequent haplogroup. For recurrence risk, 1645 patients were followed for a
mean of 5 years, during which 350 developed a recurrence (21%; MEGA follow-up
study). We calculated recurrence rates for the major haplogroups, and compared
groups by calculating hazard ratios. Results We observed 13 haplogroups, of which
R1b was the most frequent (59%). The major haplogroups were not associated with a
first VT, with odds ratios ranging from 1.01 to 1.15. Haplogroup E carriers had
the highest recurrence rate (53.5 per 1000 person-years, 95% confidence interval
[CI] 33.3-86.1), whereas haplogroup R1a carriers had the lowest recurrence rate
(24.3 per 1000 person-years, 95% CI 12.6-46.6). As compared with haplogroup R1b
carriers, both haplogroups were not significantly associated with recurrence
risk. Conclusions In contrast to a study on coronary artery disease, our results
do not show a clear predisposing effect of Y haplogroups on first and recurrent
VT risk in men. It is therefore unlikely that Y variation can explain the sex
difference in VT risk.
PMID- 27495184
TI - The Spatial Representation of Angles.
AB - We investigated whether angle magnitude, similarly to numerical quantities (i.e.,
the spatial-numerical association of response codes effect), is associated to the
side of response execution. In addition, we investigated whether this association
has the properties of a spatially oriented mental line, since angles are taught
in a right-to-left progression. We tested two groups of participants: civil
engineering students (high familiarity with angles) and psychology students (low
familiarity with angles). In Experiment 1, participants were asked to judge the
continuity of the angles' arms (continuous vs. dashed). Magnitude of the angles
was task-irrelevant. In Experiment 2, they were asked to judge whether the
presented angles were smaller or larger than a right angle (90 degrees ).
Therefore, the angle magnitude was relevant for performing the task. Overall,
engineering students responded faster with their left hand to large angles and
with their right hand to small angles. Conversely, psychology students did not
show any reliable differences between left- and right-hand responses. In the case
of engineering students, the spatial association has a right-to-left (counter
clockwise) direction, suggesting the influence of education and practice on the
mental representation of angle magnitude.
PMID- 27495180
TI - Injectable SN-38-loaded Polymeric Depots for Cancer Chemotherapy of Glioblastoma
Multiforme.
AB - PURPOSE: SN-38, a potent chemotherapeutic drug, has not been used clinically
because of its severe side effects and poor solubility. In this work, we aimed to
evaluate the effect of dose and multiple injections of SN-38-loaded polymeric
depots on antitumor efficacy and toxicity in vivo. METHODS: Preparation and
characterization of SN-38-loaded depots were performed and evaluated in vitro
using human glioblastoma cell line, U-87MG. Antitumor efficacy with different
depot administrations including dose, position of depot injection and number of
injections were evaluated in tumor model in nude mice. RESULTS: Depots
encapsulated SN-38 with high encapsulation efficiency (~98.3%). High amount of SN
38 (3.0 +/- 0.1 mg) was prolonged and controlled release over time and showed
anticancer activity against U-87MG cell line in vitro. For one course
administration, depots exhibited better antitumor efficacy and reduced toxicity
compared to free SN-38. Elevated doses and multiple injections of SN-38-loaded
depots and free SN-38 provided greater tumor growth inhibition and animal
survival. All animals received SN-38-loaded depots were well tolerated and
survived while most of those received free SN-38 died at day 30. Free SN-38
showed severe toxic effect compared to minimal toxicity from SN-38-loaded depots
which was due to lower SN-38 level in systemic circulation. Fluorescence imaging
and histopathology confirmed that SN-38 released from depots was detected
throughout tumors 35 days post administration. CONCLUSIONS: SN-38-loaded depots
were proved as a promising new treatment for highly invasive glioblastoma
multiforme with low acute toxicity due to controlled release of SN-38.
PMID- 27495185
TI - Action Video Games Improve Direction Discrimination of Parafoveal Translational
Global Motion but Not Reaction Times.
AB - Playing action video games enhances visual motion perception. However, there is
psychophysical evidence that action video games do not improve motion sensitivity
for translational global moving patterns presented in fovea. This study
investigates global motion perception in action video game players and compares
their performance to that of non-action video game players and non-video game
players. Stimuli were random dot kinematograms presented in the parafovea.
Observers discriminated the motion direction of a target random dot kinematogram
presented in one of the four visual quadrants. Action video game players showed
lower motion coherence thresholds than the other groups. However, when the task
was performed at threshold, we did not find differences between groups in terms
of distributions of reaction times. These results suggest that action video games
improve visual motion sensitivity in the near periphery of the visual field,
rather than speed response.
PMID- 27495186
TI - The effect of a monetary incentive for administrative assistants on the survey
response rate: a randomized controlled trial.
AB - BACKGROUND: There is sufficient evidence that monetary incentives are effective
in increasing survey response rates in the general population as well as with
physicians. The objective of this study was to assess the impact of a monetary
incentive intended for administrative assistants on the survey response rate of
physicians in leadership positions. METHODS: This was an ancillary study to a
national survey of chairs of academic Departments of Medicine in the United
States about measuring faculty productivity. We randomized survey participants to
receive or not receive a $5 gift card enclosed in the survey package. The cover
letter explained that the gift card was intended for the administrative
assistants as a "thank you for their time." We compared the response rates
between the 2 study arms using the Chi-square test. RESULTS: Out of 152
participants to whom survey packages were mailed to, a total of 78 responses were
received (51 % response rate). The response rates were 59 % in the incentive arm
and 46 % in the no incentive arm. The relative effect of the incentive compared
to no monetary incentive was borderline statistically significant (relative risk
(RR) = 1.36, 95 % confidence interval (CI) 0.99 to 1.87; p = 0.055). CONCLUSION:
Monetary incentives intended for administrative assistants likely increase the
response rate of physicians in leadership positions.
PMID- 27495187
TI - Intraindividual Analysis of Signal Intensity Changes in the Dentate Nucleus After
Consecutive Serial Applications of Linear and Macrocyclic Gadolinium-Based
Contrast Agents.
AB - PURPOSE: Recent studies reported an increase in the dentate nucleus (DN)-to-pons
signal intensity (SI) ratio (DN-pons SI ratio) on unenhanced T1-weighted images
in patients who received consecutive serial injections of linear gadolinium-based
contrast agents (GBCAs). In contrast, most studies found no increase in the DN
pons SI ratio when patients were treated with consecutive serial injections of
macrocyclic GBCAs. However, the potential difference between macrocyclic and
linear GBCAs has never been assessed in individuals who received subsequent
applications of both contrast agents. In this retrospective study, we assessed
the evolution of the DN-pons SI ratio change in patients that were treated with a
comparable number of serial consecutive injections of the linear GBCA
gadopentetate dimeglumine and subsequent serial injections of the macrocyclic
GBCAs gadobutrol and gadoterate meglumine. MATERIALS AND METHODS: Data of 36
patients was analyzed. All patients underwent at least 5 consecutive
administrations of the linear GBCA gadopentetate dimeglumine followed by an equal
number of consecutive administrations of the macrocyclic GBCA gadobutrol. In 12
of the 36 patients, 5 or more final consecutive injections of the macrocyclic
GBCA gadoterate meglumine were analyzed additionally. The difference of DN-pons
SI ratios on unenhanced T1-weighted images was calculated by subtracting the
ratio at the first examination from the ratio at the last examination in each of
the 3 periods. RESULTS: The mean DN-pons SI ratio difference in the gadopentetate
dimeglumine period was significantly greater than 0 (mean +/- SD, 0.0448 +/-
0.0345; P < 0.001), whereas the mean DN-pons SI ratio difference in the
subsequent gadobutrol and gadoterate meglumine period was significantly smaller
than 0 (gadobutrol: -0.0178 +/- 0.0459, P = 0.026; gadoterate meglumine: -0.0250
+/- 0.0284, P = 0.011). CONCLUSIONS: In this observational study, the application
of the linear GBCA gadopentetate dimeglumine was associated with a DN-pons SI
ratio increase, whereas subsequent applications of the macrocyclic GBCAs
gadobutrol or gadoterate meglumine in the same patients were not. Rather, the
current data tentatively suggest a decrease in preexisting hyperintensities over
time when linear GBCAs are changed to macrocyclic GBCAs, potentially indicating a
washout effect or precipitation of gadolinium. Future patient studies need to
include control groups to replicate the present results, and additional animal
studies should be conducted to clarify the underlying mechanism of the proposed
SI decrease.
PMID- 27495189
TI - High salt intake is associated with a higher risk of cardiovascular events: a 7.2
year evaluation of a cohort of hypertensive patients.
AB - BACKGROUND: It is controversial whether high salt intake is directly associated
with cardiovascular (CV) events and how far this relation is independent of blood
pressure (BP). As Portugal has higher salt consumption and higher mortality by
stroke than other European countries, we examined whether salt intake could
predict the development of stroke and CV events in a hypertensive population.
METHODS: In a longitudinal retrospective study of a cohort of 608 adult treated
hypertensive patients 54.1+/-14.3 years of age, BMI 29.3+/-8.3 kg/m, 56.3% women
and 17.1% diabetics, we evaluate the long-term prognostic significance of urinary
sodium (UNa) excretion measured in 24 h valid samples within the first 3 months
after admission along with 24 h ambulatory blood pressure monitoring and pulse
wave velocity [(PWV), complior)] measurements. RESULTS: The mean follow-up
duration was 7.2 years (0.5-11.1 years), during which 122 CV events occurred
including 80 strokes and 36 coronary events. In 608 patients (group A=507 without
events and group B=101 with events: 69 strokes, 26 coronary events, six others),
the mean 24 h UNa was 208+/-79 mmol/day, corresponding to a salt intake of 12.1+/
4.6 g/day. Twenty-four hours UNa correlated positively with BMI, PWV and systolic
blood pressure (SBP) particularly with night-time SBP. Group B versus A showed
higher UNa (260+98 vs. 198+71 mmol/day, P<0.001) and higher PWV, BP office, 24 h,
daytime and night-time SBP. Logistic regression analysis identified age, night
time SBP and 24 h UNa+ [HR=1.09 (95% CI, 1.06-1.12, P<0.001)] for each 10 mmol
increase of UNa+ as the only independent predictors of CV events. UNa+ above the
median (189 mmol sodium/day) predicted CV events with HR=2.99 (95% CI, 1.75-5.13,
P<0.001) with worse CV event-free survival rates (log rank statistics of 17.44,
P<0.001). CONCLUSION: In a cohort of hypertensive patients, high salt intake
independently predicts the occurrence of CV events, particularly of stroke.
PMID- 27495188
TI - The Use of Acoustic Radiation Force Decorrelation-Weighted Pulse Inversion for
Enhanced Ultrasound Contrast Imaging.
AB - OBJECTIVES: The use of ultrasound imaging for cancer diagnosis and screening can
be enhanced with the use of molecularly targeted microbubbles. Nonlinear imaging
strategies such as pulse inversion (PI) and "contrast pulse sequences" (CPS) can
be used to differentiate microbubble signal, but often fail to suppress highly
echogenic tissue interfaces. This failure results in false-positive detection and
potential misdiagnosis. In this study, a novel acoustic radiation force (ARF)
based approach was developed for superior microbubble signal detection. The
feasibility of this technique, termed ARF decorrelation-weighted PI (ADW-PI), was
demonstrated in vivo using a subcutaneous mouse tumor model. MATERIALS AND
METHODS: Tumors were implanted in the hindlimb of C57BL/6 mice by subcutaneous
injection of MC38 cells. Lipid-shelled microbubbles were conjugated to anti
VEGFR2 antibody and administered via bolus injection. An image sequence using ARF
pulses to generate microbubble motion was combined with PI imaging on a
Verasonics Vantage programmable scanner. ADW-PI images were generated by
combining PI images with interframe signal decorrelation data. For comparison,
CPS images of the same mouse tumor were acquired using a Siemens Sequoia clinical
scanner. RESULTS: Microbubble-bound regions in the tumor interior exhibited
significantly higher signal decorrelation than static tissue (n = 9, P < 0.001).
The application of ARF significantly increased microbubble signal decorrelation
(n = 9, P < 0.01). Using these decorrelation measurements, ADW-PI imaging
demonstrated significantly improved microbubble contrast-to-tissue ratio when
compared with corresponding CPS or PI images (n = 9, P < 0.001). Contrast-to
tissue ratio improved with ADW-PI by approximately 3 dB compared with PI images
and 2 dB compared with CPS images. CONCLUSIONS: Acoustic radiation force can be
used to generate adherent microbubble signal decorrelation without microbubble
bursting. When combined with PI, measurements of the resulting microbubble signal
decorrelation can be used to reconstruct images that exhibit superior suppression
of highly echogenic tissue interfaces when compared with PI or CPS alone.
PMID- 27495190
TI - Blood pressure cuff comparability study.
AB - BACKGROUND: Manufacturer-supplied blood pressure (BP) cuffs are part of the
automatic oscillometric BP devices algorithm. MATERIALS AND METHODS: This study
assessed the differences in BP values using the Omron HEM 907-XL (Omron) device
with two types of cuffs: the Baum cuff (BC) and the supplied Omron cuff (OC). A
sample of 102 adults participated in the study, 34 per cuff size (adult, large,
and extra-large). After a 5-min resting period, three pairs of BP determinations
(systolic and diastolic) were taken simultaneously on both arms. One arm was
cuffed with a BC and the other arm was cuffed with an OC. The cuffs were switched
to opposite arms after 5 min of rest. The order was decided randomly as to which
cuff was applied to which arm first. RESULTS: The BP readings were highly
correlated between the cuffs (systolic BP, r=0.98; diastolic BP, r=0.98). The
overall mean differences (BC-OC) were 2.66 mmHg (SD=3.9 mmHg) for systolic BP
(P<0.05) and 0.33 mmHg (SD=2.03 mmHg) for diastolic BP (P>0.05). Increased cuff
size corresponded to increased differences in systolic BP values (adult: 1.51
mmHg; large: 2.56 mmHg; and extra-large: 3.9 mmHg; P<0.05). For diastolic BP
values, a statistically significant difference was observed only for adult cuff
size (difference=1.31 mmHg, SD=1.34 mmHg, P<0.05). CONCLUSION: Using a BC with
the Omron could result in higher systolic BP readings and higher diastolic BP
readings with the adult cuff size.
PMID- 27495191
TI - Hidradenitis suppurativa associated with squamous cell carcinoma: an example of
an isoscartopic response.
PMID- 27495196
TI - A Kinetic and Nonrigid Approach to Movement Disorders.
PMID- 27495197
TI - Diagnosing Parkinson Disease.
AB - PURPOSE OF REVIEW: While establishing the diagnosis of Parkinson disease (PD) can
be straightforward, it can be challenging in some patients, even for the
experienced neurologist. The misdiagnosis rate ranges from 10% to 20% or greater
depending on clinician experience. RECENT FINDINGS: Despite promise in the search
for a biomarker that can establish the presence of PD and act as a marker of its
progression, the diagnosis of PD continues to be based on clinical examination.
Core criteria, exclusion criteria, and supportive criteria have been developed to
aid the clinician in establishing the diagnosis. Nonmotor symptoms of PD are
usually present at the time of diagnosis, may precede motor symptoms, and should
be specifically sought during evaluation. Ancillary testing can be appropriate,
but its indications and utility must be clearly understood. SUMMARY: The
diagnosis of PD requires the recognition of the core features of PD and the
differentiation of its clinical presentation from other entities with similar and
potentially overlapping symptoms. A careful history and examination guided by
clinical diagnostic criteria will usually establish the diagnosis of PD or
uncover red flags for the possibilities of other diagnoses. Appropriate selection
and interpretation of ancillary testing is critical to avoid misdiagnosis and
unnecessary tests.
PMID- 27495198
TI - Treating the Motor Symptoms of Parkinson Disease.
AB - PURPOSE OF REVIEW: After a patient is diagnosed with Parkinson disease (PD),
there are many therapeutic options available. This article provides examples of
prototypical patients encountered in clinical practice and illustrates the
various pharmacologic and nonpharmacologic treatment options for the motor
symptoms of PD. RECENT FINDINGS: Levodopa became available in the late 1960s and
remains the gold standard for the treatment of PD even today. Since that time,
amantadine, monoamine oxidase type B inhibitors, dopamine agonists, and catechol
O-methyltransferase inhibitors have emerged as monotherapy, add-on therapies, or
both, in the armamentarium against PD. The most appropriate time to start such
drugs remains a clinical decision according to patient symptoms. However, earlier
use of levodopa is the more common practice due to its superior benefit and the
side effects of dopamine agonists. Deep brain stimulation continues to be the
most effective treatment for motor symptoms in appropriate patients, and advances
in technology may improve efficacy. New ways to deliver levodopa have emerged
(effective extended-release oral preparations and levodopa/carbidopa intestinal
gel), and these medications provide additional options for certain patients.
Exercise and neurorehabilitation are increasingly recognized as important tools
to combat the motor symptoms of PD. Nondopaminergic drugs may help non-levodopa
responsive motor symptoms. SUMMARY: Treatment of PD is multifaceted and requires
a tailored pharmacotherapeutic and nonpharmacologic approach for a given patient.
Patients should be at the center of care, and clinicians should try to provide
optimum benefit through the many treatment options available.
PMID- 27495192
TI - The inhibitor of semicarbazide-sensitive amine oxidase, PXS-4728A, ameliorates
key features of chronic obstructive pulmonary disease in a mouse model.
AB - BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major
cause of illness and death, often induced by cigarette smoking (CS). It is
characterized by pulmonary inflammation and fibrosis that impairs lung function.
Existing treatments aim to control symptoms but have low efficacy, and there are
no broadly effective treatments. A new potential target is the ectoenzyme,
semicarbazide-sensitive mono-amine oxidase (SSAO; also known as vascular adhesion
protein-1). SSAO is elevated in smokers' serum and is a pro-inflammatory enzyme
facilitating adhesion and transmigration of leukocytes from the vasculature to
sites of inflammation. EXPERIMENTAL APPROACH: PXS-4728A was developed as a low MW
inhibitor of SSAO. A model of COPD induced by CS in mice reproduces key aspects
of human COPD, including chronic airway inflammation, fibrosis and impaired lung
function. This model was used to assess suppression of SSAO activity and
amelioration of inflammation and other characteristic features of COPD. KEY
RESULTS: Treatment with PXS-4728A completely inhibited lung and systemic SSAO
activity induced by acute and chronic CS-exposure. Daily oral treatment inhibited
airway inflammation (immune cell influx and inflammatory factors) induced by
acute CS-exposure. Therapeutic treatment during chronic CS-exposure, when the key
features of experimental COPD develop and progress, substantially suppressed
inflammatory cell influx and fibrosis in the airways and improved lung function.
CONCLUSIONS AND IMPLICATIONS: Treatment with a low MW inhibitor of SSAO, PXS
4728A, suppressed airway inflammation and fibrosis and improved lung function in
experimental COPD, demonstrating the therapeutic potential of PXS-4728A for this
debilitating disease.
PMID- 27495199
TI - Neuropsychiatric Issues in Parkinson Disease.
AB - PURPOSE OF REVIEW: This article reviews the recognition and management of
neuropsychiatric issues in Parkinson disease (PD), including mood disorders,
cognitive impairment, and behavioral disturbances. RECENT FINDINGS: Patients with
PD frequently develop neuropsychiatric issues, and these issues can greatly
affect their quality of life. In recent years, mood, cognitive, and behavioral
issues in PD have received greater recognition, with increasing attention
directed toward improved screening and therapeutic interventions for symptomatic
treatment. Taken together as a group, neuropsychiatric issues can be found
throughout the whole course of PD, from early in the disease, potentially even in
a premotor stage, to the time of diagnosis and later in the course with more
advanced disease. SUMMARY: In the comprehensive care of patients with PD,
recognition of neuropsychiatric issues is critical. Advances in therapeutics for
the different neuropsychiatric symptoms are still needed, although several
pharmacologic and nonpharmacologic options are available. Patient management
frequently requires a multidisciplinary approach, with collaboration of
neurologists with neuropsychologists, psychologists, psychiatrists, and other
health professionals.
PMID- 27495200
TI - Treatment of Advanced Parkinson Disease and Related Disorders.
AB - PURPOSE OF REVIEW: Parkinson disease often spans decades of a patient's lifetime.
Over time, nonmotor symptoms predominate and may limit dopaminergic therapy.
Neurologists continue to play a vital role in treatment. In addition to balancing
neurobehavioral complications of Parkinson disease with motor benefit, addressing
nonmotor symptoms common in the advanced stage may improve quality of life and
reduce symptom burden. Symptoms such as dysphagia, constipation, urinary
dysfunction, orthostatic hypotension, and pain respond to nonpharmacologic and
pharmacologic therapies. RECENT FINDINGS: Evidence for treatment of many nonmotor
symptoms is weak or lacking. The evidence for treatment of the atypical
parkinsonian syndromes (progressive supranuclear palsy, multiple system atrophy,
and corticobasal degeneration) in advanced stages is even more scant. SUMMARY:
Engaging palliative care physicians in the joint care of patients can provide
patients with access to expertise in end-of-life issues. Neurologic illnesses
have specific hospice criteria to guide clinicians for referrals. Evidence
supports that assisting patients with advance directives can result in improved
satisfaction with care and improved quality of life in the last weeks of life.
Neurologists can remain engaged in their patients' care throughout the course of
illness.
PMID- 27495202
TI - Diagnosis and Management of Tremor.
AB - PURPOSE OF REVIEW: Tremor, which is a rhythmic oscillation of a body part, is
among the most common involuntary movements. Rhythmic oscillations may manifest
in a variety of ways; as a result, a rich clinical phenomenology surrounds
tremor. For this reason, diagnosing tremor disorders can be particularly
challenging. The aim of this article is to provide the reader with a
straightforward approach to the diagnosis and management of patients with tremor.
RECENT FINDINGS: Scientific understanding of the pathophysiologic basis of tremor
disorders has grown considerably in recent years with the use of a broad range of
neuroimaging approaches and rigorous, controlled postmortem studies. The basal
ganglia and cerebellum are structures that seem to play a prominent role.
SUMMARY: The diagnosis of tremor disorders is challenging. The approach to tremor
involves a history and a neurologic examination that is focused on the nuances of
tremor phenomenology, of which there are many. The evaluation should begin with a
tremor history and a focused neurologic examination. The examination should
attend to the many subtleties of tremor phenomenology. Among other things, the
history and examination are used to establish whether the main type of tremor is
an action tremor (ie, postural, kinetic, or intention tremor) or a resting
tremor. The clinician should then formulate two sets of differential diagnoses:
disorders in which action tremor is the predominant tremor versus those in which
resting tremor is the main tremor. Among the most common of the former type are
essential tremor, enhanced physiologic tremor, drug-induced tremor, dystonic
tremor, orthostatic tremor, and cerebellar tremor. Parkinson disease is the most
common form of resting tremor, along with drug-induced resting tremor. This
article details the clinical features of each of these as well as other tremor
disorders.
PMID- 27495201
TI - Diagnostic Approach to Atypical Parkinsonian Syndromes.
AB - PURPOSE OF REVIEW: Although increasingly recognized, atypical parkinsonian
syndromes remain challenging to diagnose and are underrecognized due to overlap
with other parkinsonisms. This article provides a diagnostic approach to atypical
parkinsonian syndromes, including progressive supranuclear palsy (PSP), multiple
system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy
bodies. The goal of this review is to aid the clinician in recognizing key
clinical and pathologic features and to raise awareness of recent advances in
diagnostics and treatment. RECENT FINDINGS: Diagnostic criteria for atypical
parkinsonian syndromes are evolving to encompass increasingly recognized
heterogeneity in the presentation of these disorders and information gleamed from
clinicopathologic correlations. PSP and CBD in particular now share similar
pathologic clinical features and include a number of phenotypic variants.
Pathologic diagnoses are increasingly used in clinical practice, and there is
frequent reference now by clinicians to tauopathies, including PSP and CBD, and
the synucleinopathies, which include MSA and dementia with Lewy bodies (as well
as Parkinson disease). Research into biomarkers, including both tissue and
imaging modalities and genetics, has the potential to increase disease
recognition and make earlier diagnosis and treatment possible. Although novel
therapeutics are being studied for atypical parkinsonian syndromes such as PSP,
no new breakthrough interventions have emerged for the treatment of PSP, CBD, and
MSA. Current therapeutic management for these disorders frequently uses a
multidisciplinary team approach. SUMMARY: The approach to atypical parkinsonian
syndromes requires recognition of a constellation of overlapping but distinct
clinical features that help with identifying and distinguishing them from
Parkinson disease and other similar disorders.
PMID- 27495203
TI - Movement Disorders Presenting in Childhood.
AB - PURPOSE OF REVIEW: This article provides an overview of movement disorders that
present in childhood. Key clinical features are discussed, and a brief guide to
management strategies is provided. Recent advances in the field of pediatric
movement disorders are also a focus of the article. RECENT FINDINGS: Advances in
genetic technologies and cell biology have contributed greatly to the elucidation
of underlying disease mechanisms in childhood movement disorders. This article
discusses the expanding spectrum of both genetic and acquired movement disorders
that present in childhood, including benign, acquired, genetic, and psychogenic
movement disorders. SUMMARY: Movement disorders in childhood comprise a wide
spectrum of both genetic and acquired diseases, ranging from benign self-limiting
conditions to more progressive phenotypes associated with significant morbidity
and mortality. Elucidation of the underlying cause is achieved through accurate
history, detailed clinical examination, review of video footage (including home
videos), and, where appropriate, neuroimaging and laboratory investigations.
Early accurate diagnosis will facilitate the instigation of appropriate
management strategies.
PMID- 27495204
TI - Chorea.
AB - PURPOSE OF REVIEW: This article reviews the clinical approach to the diagnosis of
adult patients presenting with chorea, using Huntington disease (HD) as a point
of reference, and presents the clinical elements that help in the diagnostic
workup. Principles of management for chorea and some of the associated features
of other choreic syndromes are also described. RECENT FINDINGS: Mutations in the
C9orf72 gene, previously identified in families with a history of frontotemporal
dementia, amyotrophic lateral sclerosis, or both, have been recognized as one of
the most prevalent causes of HD phenocopies in the white population. SUMMARY: The
diagnosis of chorea in adult patients is challenging. A varied number of
associated causes require a physician to prioritize the investigations, and a
detailed history of chorea and associated findings will help. For chorea
presenting as part of a neurodegenerative syndrome, the consideration of a
mutation in the C9orf72 gene is a new recommendation after excluding HD. There
are no new treatment options for chorea, aside from dopamine blockers and
tetrabenazine. There are no disease-modifying treatments for HD or other
neurodegenerative choreic syndromes.
PMID- 27495205
TI - Ataxia.
AB - PURPOSE OF REVIEW: This article introduces the background and common etiologies
of ataxia and provides a general approach to assessing and managing the patient
with ataxia. RECENT FINDINGS: Ataxia is a manifestation of a variety of disease
processes, and an underlying etiology needs to be investigated. Pure ataxia is
rare in acquired ataxia disorders, and associated symptoms and signs almost
always exist to suggest an underlying cause. While the spectrum of hereditary
degenerative ataxias is expanding, special attention should be addressed to those
treatable and reversible etiologies, especially potentially life-threatening
causes. This article summarizes the diseases that can present with ataxia, with
special attention given to diagnostically useful features. While emerging genetic
tests are becoming increasingly available for hereditary ataxia, they cannot
replace conventional diagnostic procedures in most patients with ataxia. Special
consideration should be focused on clinical features when selecting a cost
effective diagnostic test. SUMMARY: Clinicians who evaluate patients with ataxia
should be familiar with the disease spectrum that can present with ataxia.
Following a detailed history and neurologic examination, proper diagnostic tests
can be designed to confirm the clinical working diagnosis.
PMID- 27495206
TI - Diagnosis and Management of Dystonia.
AB - PURPOSE OF REVIEW: This article highlights the clinical and diagnostic tools used
to assess and classify dystonia and provides an overview of the treatment
approach. RECENT FINDINGS: In the past 4 years, the definition and classification
of dystonia have been revised, and new genes have been identified in patients
with isolated hereditary dystonia (DYT23, DYT24, and DYT25). Expanded phenotypes
were reported in patients with combined dystonia, such as those with mutations in
ATP1A3. Treatment offerings have expanded as there are more neurotoxins, and deep
brain stimulation has been employed successfully in diverse populations of
patients with dystonia. SUMMARY: Diagnosis of dystonia rests upon a clinical
assessment that requires the examiner to understand the characteristic disease
features that are elicited through a careful history and physical examination.
The revised classification system uses two distinct nonoverlapping axes: clinical
features and etiology. A growing understanding exists of both isolated and
combined dystonia as new genes are identified and our knowledge of the phenotypic
presentation of previously reported genes has expanded. Genetic testing is
commercially available for some of these conditions. Treatment options for
dystonia include pharmacologic therapy, chemodenervation, and surgical
intervention. Deep brain stimulation benefits many patients with various types of
dystonia.
PMID- 27495207
TI - Wilson Disease.
AB - PURPOSE OF REVIEW: This article reviews the clinical features of Wilson disease,
focusing on the neurologic and psychiatric abnormalities, and addresses the
diagnostic workup and treatment approaches to managing the disease. RECENT
FINDINGS: The list of known mutations causing Wilson disease continues to grow,
but advances in genetic testing may soon make it feasible to routinely perform
genetic testing on individuals suspected of having Wilson disease. SUMMARY:
Wilson disease is a rare genetic disorder with protean manifestations that should
be considered in the differential diagnosis of any individual presenting with
unexplained neurologic, psychiatric, or hepatic dysfunction. Appropriate
diagnostic testing should be expeditiously performed and treatment promptly
initiated and maintained since failure to diagnose and treat Wilson disease will
result in progressive and ultimately irreversible damage to the neurologic and
other systems.
PMID- 27495208
TI - Ethics of Preclinical Dopamine Transporter Imaging.
AB - While dopamine transporter single-photon emission computed tomography (DAT-SPECT)
imaging is sensitive and specific when performed in patients with signs or
symptoms of parkinsonism, its predictive value is uncertain in healthy subjects,
even with patients who have first-degree relatives affected by Parkinson disease.
In deciding whether to honor a patient's request for a DAT-SPECT, neurologists
must balance a patient's autonomy rights with beneficence and nonmaleficence and
also consider the distributive justice implications of ordering the test.
Generally speaking, the benefits of a DAT-SPECT will be too small to justify its
use in an asymptomatic patient concerned about developing Parkinson disease.
PMID- 27495209
TI - Chemodenervation Coding for Neurologists.
PMID- 27495213
TI - Patient Management Problem.
PMID- 27495214
TI - Patient Management Problem-Preferred Responses.
PMID- 27495216
TI - NICE calls for wider supply of condoms to reduce STIs.
PMID- 27495217
TI - Diagnostic hepatic haemodynamic techniques: safety and radiation exposure.
AB - BACKGROUND & AIMS: Hepatic venous pressure gradient (HVPG) and transjugular liver
biopsy (TJLB) are increasingly used in the management of patients with liver
disease. We aimed to describe the safety profile of these procedures, providing
data on the intra- and periprocedure complications, radiation exposure and amount
of iodinated contrast material used. METHODS: In 106 consecutive patients
undergoing HVPG and TJLB data on fluoroscopy time (FT), absorbed radiation dose,
equivalent effective dose (mSv) and volume of iodinated contrast material (ICM)
were prospectively collected and reviewed, together with clinical and laboratory
data. Incidence and severity of procedure-related complications were assessed. In
28 hospitalised patients, creatinine values after 72 hours of the procedure were
reviewed to identify contrast-induced nephropathy (CIN). RESULTS: Median
effective radiation dose was 5.4 mSv (IQR 10 mSv). A total 28.3% of patients
exceeded an effective exposure of 10 mSv and 9.4% exceeded 20 mSv. Only age and
BMI correlated with radiation dose (R = .327, P=.001 and R = .410, P<.0001
respectively), and only BMI remained independently associated with an exposure
over 20 mSv. Procedure-related complications occurred in eight patients (7.5%),
and were minor in six cases. Median ICM volume was 12.5 mL. 6/28 patients met the
diagnostic criteria for CIN. CONCLUSIONS: Hepatic venous pressure gradient and
Transjugular liver biopsy show a good safety profile and radiation exposure
associated with these procedures is in most of the cases low. In hepatic
haemodynamic procedures, efforts should be made to reduce the radiation dose in
patients with overweight/obesity and to use the minimal possible ICM volume in
patients with acute-on-chronic liver failure.
PMID- 27495218
TI - Status epilepticus alters hippocampal long-term synaptic potentiation in a rat
lithium-pilocarpine model.
AB - Seizure-induced memory deficits are frequent in patients with temporal lobe
epilepsy. However, the neural mechanisms responsible for this memory impairment
are not entirely clear. Persistent changes in synaptic efficacy, long-term
potentiation (LTP), and depression are considered a cellular substrate underlying
the learning and memory processes. Using a lithium-pilocarpine model to induce
status epilepticus (SE) in rats, the present study investigated whether the
induction of LTP was altered in hippocampal slices obtained 3 h, 1, 3, and 7 days
after SE. One week after SE, LTP induction was decreased in hippocampal slices.
The reduced plasticity in post-SE tissue was attributable to N-methyl-D-aspartate
receptor-dependent LTP. In contrast to control tissue, ifenprodil, a GluN2B
selective antagonist, did not reduce the LTP level in post-SE tissue, suggesting
that SE disturbs the functional properties of GluN2B-containing N-methyl-D
aspartate receptors. These changes in synaptic transmission may contribute toward
the genesis of epilepsy and seizure-associated memory deficits.
PMID- 27495219
TI - Cathodal transcranial direct current stimulation of the posterior parietal cortex
reduces steady-state postural stability during the effect of light touch.
AB - Touching a stable object with a fingertip using slight force (<1 N) stabilizes
standing posture independent of mechanical support, which is referred to as the
effect of light touch (LT). In the neural mechanism of the effect of LT, the
specific contribution of the cortical brain activity toward the effect of LT
remains undefined, particularly the contribution toward steady-state postural
sway. The aim of the present study was to investigate the cortical region
responsible for the reduction of postural sway in response to the effect of LT.
Active LT was applied with the right fingertip and transcranial direct current
stimulation (sham or cathodal) was applied to the left primary sensorimotor
cortex or the left posterior parietal cortex in the two groups. The experiments
were conducted using a single-blind sham-controlled crossover design. Steady
state postural sway was compared with the factors of transcranial direct current
stimulation (sham or cathodal) and time (pre or post). In the results, the effect
of LT reduced postural stability in the mediolateral direction after cathodal
transcranial direct current stimulation of the left posterior parietal cortex. No
effect was observed after stimulation of the left primary sensorimotor cortex.
This indicates that the left posterior parietal cortex is partly responsible for
the effect of LT when touching a fixed point with the right fingertip during
suprapostural tasks, where posture is adjusted according to the precision
requirements. Cortical processing of sensory integration for voluntary postural
orientation in response to touch occurs in the posterior parietal cortex.
PMID- 27495220
TI - Renal Denervation Reverses Hepatic Insulin Resistance Induced by High-Fat Diet.
AB - Activation of the sympathetic nervous system (SNS) constitutes a putative
mechanism of obesity-induced insulin resistance. Thus, we hypothesized that
inhibiting the SNS by using renal denervation (RDN) will improve insulin
sensitivity (SI) in a nonhypertensive obese canine model. SI was measured using
euglycemic-hyperinsulinemic clamp (EGC), before (week 0 [w0]) and after 6 weeks
of high-fat diet (w6-HFD) feeding and after either RDN (HFD + RDN) or sham
surgery (HFD + sham). As expected, HFD induced insulin resistance in the liver
(sham 2.5 +/- 0.6 vs. 0.7 +/- 0.6 * 10-4 dL ? kg-1 ? min-1 ? pmol/L-1 at w0 vs.
w6-HFD [P < 0.05], respectively; HFD + RDN 1.6 +/- 0.3 vs. 0.5 +/- 0.3 * 10-4 dL
? kg-1 ? min-1 ? pmol/L-1 at w0 vs. w6-HFD [P < 0.001], respectively). In sham
animals, this insulin resistance persisted, yet RDN completely normalized hepatic
SI in HFD-fed animals (1.8 +/- 0.3 * 10-4 dL ? kg-1 ? min-1 ? pmol/L-1 at HFD +
RDN [P < 0.001] vs. w6-HFD, [P not significant] vs. w0) by reducing hepatic
gluconeogenic genes, including G6Pase, PEPCK, and FOXO1. The data suggest that
RDN downregulated hepatic gluconeogenesis primarily by upregulating liver X
receptor alpha through the natriuretic peptide pathway. In conclusion, bilateral
RDN completely normalizes hepatic SI in obese canines. These preclinical data
implicate a novel mechanistic role for the renal nerves in the regulation of
insulin action specifically at the level of the liver and show that the renal
nerves constitute a new therapeutic target to counteract insulin resistance.
PMID- 27495222
TI - Impaired Cardiolipin Biosynthesis Prevents Hepatic Steatosis and Diet-Induced
Obesity.
AB - Mitochondria are the nexus of energy metabolism, and consequently their
dysfunction has been implicated in the development of metabolic complications and
progression to insulin resistance and type 2 diabetes. The unique tetra-acyl
phospholipid cardiolipin (CL) is located in the inner mitochondrial membrane,
where it maintains mitochondrial integrity. Here we show that knockdown of
Tafazzin (TAZ kd), a CL transacylase, in mice results in protection against the
development of obesity, insulin resistance, and hepatic steatosis. We determined
that hypermetabolism protected TAZ kd mice from weight gain. Unexpectedly, the
large reduction of CL in the heart and skeletal muscle of TAZ kd mice was not
mirrored in the liver. As a result, TAZ kd mice exhibited normal hepatic
mitochondrial supercomplex formation and elevated hepatic fatty acid oxidation.
Collectively, these studies identify a key role for hepatic CL remodeling in
regulating susceptibility to insulin resistance and as a novel therapeutic target
for diet-induced obesity.
PMID- 27495221
TI - Enhanced Integrin alpha4beta1-Mediated Adhesion Contributes to a Mobilization
Defect of Endothelial Progenitor Cells in Diabetes.
AB - Diabetes is associated with a deficit of circulating endothelial progenitor cells
(EPCs), which has been attributed to their defective mobilization from the bone
marrow. The basis for this mobilization defect is not completely understood, and
we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We
found that culturing EPCs in high glucose media increased adhesion to bone marrow
stromal cells. This enhanced adhesion was associated with decreased expression of
protein kinase A regulatory subunit 1beta (PRKAR1beta), activation of protein
kinase A (PKA), and phosphorylation of alpha4-integrin on serine 988. This
potentiated adhesion was reversed by treatment with a PKA inhibitor,
overexpression of PRKAR1beta, or expression of a phosphorylation-defective alpha4
integrin variant (alpha4[S988A]). Using a model of type 1 diabetes, we showed
that alpha4(S988A)-expressing mice have more circulating EPCs than their wild
type counterparts. Moreover, diabetic alpha4(S988A) mice demonstrate enhanced
revascularization after hind limb ischemia. Thus, we have identified a novel
signaling mechanism activating PKA in diabetes (downregulation of an inhibitory
regulatory subunit) that leads to deficits of circulating EPCs and impaired
vascular repair, which could be reversed by alpha4-integrin mutation.
PMID- 27495223
TI - MicroRNA-451 Negatively Regulates Hepatic Glucose Production and Glucose
Homeostasis by Targeting Glycerol Kinase-Mediated Gluconeogenesis.
AB - MicroRNAs (miRNAs) are a new class of regulatory molecules implicated in type 2
diabetes, which is characterized by insulin resistance and hepatic glucose
overproduction. We show that miRNA-451 (miR-451) is elevated in the liver tissues
of dietary and genetic mouse models of diabetes. Through an adenovirus-mediated
gain- and loss-of-function study, we found that miR-451 negatively regulates
hepatic gluconeogenesis and blood glucose levels in normal mice and identified
glycerol kinase (Gyk) as a direct target of miR-451. We demonstrate that miR-451
and Gyk regulate hepatic glucose production, the glycerol gluconeogenesis axis,
and the AKT-FOXO1-PEPCK/G6Pase pathway in an opposite manner; Gyk could reverse
the effect of miR-451 on hepatic gluconeogenesis and AKT-FOXO1-PEPCK/G6Pase
pathway. Moreover, overexpression of miR-451 or knockdown of Gyk in diabetic mice
significantly inhibited hepatic gluconeogenesis, alleviated hyperglycemia, and
improved glucose tolerance. Further studies showed that miR-451 is upregulated by
glucose and insulin in hepatocytes; the elevation of hepatic miR-451 in diabetic
mice may contribute to inhibiting Gyk expression. This study provides the first
evidence that miR-451 and Gyk regulate the AKT-FOXO1-PEPCK/G6Pase pathway and
play critical roles in hepatic gluconeogenesis and glucose homeostasis and
identifies miR-451 and Gyk as potential therapeutic targets against hyperglycemia
in diabetes.
PMID- 27495224
TI - Peripheral Proinsulin Expression Controls Low-Avidity Proinsulin-Reactive CD8 T
Cells in Type 1 Diabetes.
AB - Low-avidity autoreactive CD8 T cells (CTLs) escape from thymic negative
selection, and peripheral tolerance mechanisms are essential for their
regulation. We report the role of proinsulin (PI) expression on the development
and activation of insulin-specific CTLs in the NOD mouse model of type 1
diabetes. We studied insulin B-chain-specific CTL from different T-cell receptor
transgenic mice (G9Calpha-/-) expressing normal PI1 and PI2 or altered PI
expression levels. In the absence of PI2 (Ins2-/-), CTL in pancreatic lymph nodes
(PLNs) were more activated, and male G9Calpha-/- mice developed T1D. Furthermore,
when the insulin-specific CTLs developed in transgenic mice lacking their
specific PI epitope, the CTLs demonstrated increased cytotoxicity and
proliferation in vitro and in vivo in the PLNs after adoptive transfer into NOD
recipients. Dendritic cell-stimulated proliferation of insulin-specific T cells
was reduced in the presence of lymph node stromal cells (LNSCs) from NOD mice but
not from mice lacking the PI epitope. Our study shows that LNSCs regulate CTL
activation and suggests that exposure to PI in the periphery is very important in
maintenance of tolerance of autoreactive T cells. This is relevant for human type
1 diabetes and has implications for the use of antigen-specific therapy in
tolerance induction.
PMID- 27495225
TI - Reduced beta-Cell Secretory Capacity in Pancreatic-Insufficient, but Not
Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.
AB - Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased
risk for developing diabetes. We determined beta-cell secretory capacity and
insulin secretory rates from glucose-potentiated arginine and mixed-meal
tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis
(PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance,
in order to identify early pathophysiologic defects. Acute islet cell secretory
responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia
clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon
responses compared with PS-CF and normal control subjects, indicating reduced
beta-cell secretory capacity and alpha-cell function. Fasting proinsulin-to-C
peptide and proinsulin secretory ratios during glucose potentiation were higher
in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the
MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control
subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were
lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF
compared with normal control subjects. These findings indicate that despite
"normal" glucose tolerance, adolescents and adults with PI-CF have impairments in
functional islet mass and associated early-phase insulin secretion, which with
decreased incretin responses likely leads to the early development of
postprandial hyperglycemia in CF.
PMID- 27495226
TI - A Direct Comparison of Metabolic Responses to High-Fat Diet in C57BL/6J and
C57BL/6NJ Mice.
AB - Although nicotinamide nucleotide transhydrogenase (NNT)-deficient C57BL/6J (6J)
mice are known to be highly susceptible to diet-induced metabolic disease, this
notion stems primarily from comparisons of 6J mice to other inbred strains. To
date, very few studies have directly compared metabolic disease susceptibility
between NNT-deficient 6J mice and NNT-competent C57BL/6 substrains. In this
study, comprehensive profiling of the metabolic response to a high-fat/high
sucrose diet (HFD) were compared across time in 6J and C57BL/6NJ (6N) mice. Given
that increased peroxide exposure drives insulin resistance, coupled with the fact
that NNT regulates peroxide detoxification, it was hypothesized that 6J mice
would experience greater derangements in redox homeostasis/metabolic disease upon
HFD exposure. Contrary to this, both lines were found to be highly susceptible to
diet-induced metabolic disease, as evidenced by impairments in glucose tolerance
as early as 24 h into the HFD. Moreover, various markers of the metabolic
syndrome, as well as peroxide stress, were actually blunted, rather than
exacerbated, in the 6J mice, likely reflecting compensatory increases in
alterative redox-buffering pathways. Together, these data provide evidence that
the susceptibility to HFD-induced metabolic disease is similar in the 6J and 6N
substrains. Given the numerous genetic variances in the 6J stain, including loss
of NNT function, these findings suggest that the 6N substrain is the more logical
and representative genetic background model for metabolic studies.
PMID- 27495227
TI - Chemical disguise of myrmecophilous cockroaches and its implications for
understanding nestmate recognition mechanisms in leaf-cutting ants.
AB - BACKGROUND: Cockroaches of the genus Attaphila regularly occur in leaf-cutting
ant colonies. The ants farm a fungus that the cockroaches also appear to feed on.
Cockroaches disperse between colonies horizontally (via foraging trails) and
vertically (attached to queens on their mating flights). We analysed the chemical
strategies used by the cockroaches to integrate into colonies of Atta colombica
and Acromyrmex octospinosus. Analysing cockroaches from nests of two host species
further allowed us to test the hypothesis that nestmate recognition is based on
an asymmetric mechanism. Specifically, we test the U-present nestmate recognition
model, which assumes that detection of undesirable cues (non-nestmate specific
substances) leads to strong rejection of the cue-bearers, while absence of
desirable cues (nestmate-specific substances) does not necessarily trigger
aggression. RESULTS: We found that nests of Atta and Acromyrmex contained
cockroaches of two different and not yet described Attaphila species. The
cockroaches share the cuticular chemical substances of their specific host
species and copy their host nest's colony-specific cuticular profile. Indeed, the
cockroaches are accepted by nestmate but attacked by non-nestmate ant workers.
Cockroaches from Acromyrmex colonies bear a lower concentration of cuticular
substances and are less likely to be attacked by non-nestmate ants than
cockroaches from Atta colonies. CONCLUSIONS: Nest-specific recognition of
Attaphila cockroaches by host workers in combination with nest-specific cuticular
chemical profiles suggest that the cockroaches mimic their host's recognition
labels, either by synthesizing nest-specific substances or by substance transfer
from ants. Our finding that the cockroach species with lower concentration of
cuticular substances receives less aggression by both host species fully supports
the U-present nestmate recognition model. Leaf-cutting ant nestmate recognition
is thus asymmetric, responding more strongly to differences than to similarities.
PMID- 27495228
TI - Unsuspected pulmonary embolism: a diagnostic dilemma.
PMID- 27495229
TI - The role and impact of research positions within health care settings in allied
health: a systematic review.
AB - BACKGROUND: Embedding dedicated research positions within healthcare settings is
a potential strategy to build allied health research capacity, with different
health care organisations investing in such positions. The aim of this review was
to gather evidence regarding the nature of the role of the research position in
allied health professional (AHP) healthcare settings and the impact that these
positions have on building research capacity. METHODS: A systematic review was
undertaken searching eight databases (Medline CINAHL, Cochrane, OTSeeker,
Speechbite, PEDro, Web of Science, and Proquest) using English language
restrictions. Both authors independently screened abstracts, reviewed full-text
articles, extracted data and performed quality assessments using the Mixed
Methods Appraisal Tool. Studies were included that reported the evaluation and/or
components of the role of a dedicated research position with AHPs in any
healthcare setting. A thematic analysis approach was used to synthesise findings.
RESULTS: A total of 360 abstracts were initially screened, with 58 full text
articles being reviewed. Eight unique studies were included in the thematic
analysis clarifying either the nature of role of the research position (n = 7) or
impact of the position (n = 4). Studies included mixed methods (n = 3),
descriptive case study (n = 4), and observational (n = 1) designs. The majority
of studies reported the research positions to provide academic support to
individual clinicians and their teams, while developing their own research
projects. Other studies reported support for research capacity building at a
service and organisational level. Positive changes from these research positions
was reported via increased individual research skills and participation and
research outputs, improvements in research culture, attitudes and team and
organisational level skills. CONCLUSION: Emerging evidence suggests that research
positions embedded within healthcare settings can influence individual and team
based research skills and research participation of AHPs. Future research is
needed to further investigate the sustainability of changes arisen from research
positions and what mechanisms of the positions have the greatest impact.
Healthcare managers should consider how to support potential components of the
research position roles identified in the literature, as well consider evaluating
their impact on research capacity, cultural and attitudinal changes of AHP staff
in addition to traditional research metrics.
PMID- 27495231
TI - FGF9, activin and TGFbeta promote testicular characteristics in an XX gonad organ
culture model.
AB - Testis development is dependent on the key sex-determining factors SRY and SOX9,
which activate the essential ligand FGF9. Although FGF9 plays a central role in
testis development, it is unable to induce testis formation on its own. However,
other growth factors, including activins and TGFbetas, also present testis during
testis formation. In this study, we investigated the potential of FGF9 combined
with activin and TGFbeta to induce testis development in cultured XX gonads. Our
data demonstrated differing individual and combined abilities of FGF9, activin
and TGFbeta to promote supporting cell proliferation, Sertoli cell development
and male germ line differentiation in cultured XX gonads. FGF9 promoted
proliferation of supporting cells in XX foetal gonads at rates similar to those
observed in vivo during testis cord formation in XY gonads but was insufficient
to initiate testis development. However, when FGF9, activin and TGFbeta were
combined, aspects of testicular development were induced, including the
expression of Sox9, morphological reorganisation of the gonad and deposition of
laminin around germ cells. Enhancing beta-catenin activity diminished the testis
promoting activities of the combined growth factors. The male promoting activity
of FGF9 and the combined growth factors directly or indirectly extended to the
germ line, in which a mixed phenotype was observed. FGF9 and the combined growth
factors promoted male germ line development, including mitotic arrest, but
expression of pluripotency genes was maintained, rather than being repressed.
Together, our data provide evidence that combined signalling by FGF9, activin and
TGFbeta can induce testicular characteristics in XX gonads.
PMID- 27495230
TI - Spatiotemporal dynamics of OCT4 protein localization during preimplantation
development in mice.
AB - Spatiotemporal expression of transcription factors is crucial for genomic
reprogramming. Pou5f1 (Oct4) is an essential transcription factor for
reprogramming. A recent study reported that OCT4A, which is crucial for
establishment and maintenance of pluripotent cells, is expressed in oocytes, but
maternal OCT4A is dispensable for totipotency induction. Whereas another study
reported that OCT4B, which is not related to pluripotency, is predominantly
expressed instead of OCT4A during early preimplantation phases in mice. To
determine the expression states of OCT4 in murine preimplantation embryos, we
conducted in-depth expression and functional analyses. We found that pluripotency
related OCT4 mainly localizes to the cytoplasm in early preimplantation phases,
with no major nuclear localization until the 8-16-cell stage despite high
expression in both oocytes and early embryos. RNA-sequencing analysis using
oocytes and early preimplantation embryos could not identify the splice variants
creating alternative forms of OCT4 protein. Forced expression of OCT4 in zygotes
by the injection of polyadenylated mRNA clearly showed nuclear localization of
OCT4 protein around 3-5-fold greater than physiological levels and impaired
developmental competency in a dose-dependent manner. Embryos with modest
overexpression of OCT4 could develop to the 16-cell stage; however, more than 50%
of the embryos were arrested at this stage, similar to the results for OCT4
depletion. In contrast, extensive overexpression of OCT4 resulted in complete
arrest at the 2-cell stage accompanied by downregulation of zygotically activated
genes and repetitive elements related to the totipotent state. These results
demonstrated that OCT4 protein localization was spatiotemporally altered during
preimplantation development, and strict control of Oct4 protein levels was
essential for proper totipotential reprogramming.
PMID- 27495232
TI - Quercetin modulates Wnt signaling components in prostate cancer cell line by
inhibiting cell viability, migration, and metastases.
AB - Epithelial-mesenchymal transition (EMT) is a plastic transition in tumor
progression during which cancer cells undergo dramatic changes acquiring highly
invasive properties. Transforming growth factor-beta (TGF-beta) is an inducer of
EMT in epithelial cells and is obligatory for acquiring invasive phenotype in
carcinoma. TGF-beta plays a vital role in metastasis and tumorigenesis in
prostate cancer, and mutations in the components of Wnt signaling pathways are
associated with various kinds of cancers including prostate cancer. The purpose
of this study was to identify alterations in Wnt signaling pathway components
involved during prostate cancer progression and to determine the effect of
quercetin on TGF-beta-induced EMT in prostate cancer (PC-3) cell line. The
expression of epithelial and mesenchymal markers and the components of Wnt
signaling pathway were evaluated by real-time polymerase chain reaction. It was
observed that quercetin prevented TGF-beta-induced expression of vimentin and N
cadherin and increased the expression of E-cadherin in PC-3 cells, thus
preventing TGF-beta-induced EMT. Furthermore, the relative expression of Twist,
Snail, and Slug showed that quercetin significantly decreased TGF-beta-induced
expression of Twist, Snail, and Slug. In the present study, the expression of
epithelial markers were found to be upregulated in naive state and downregulated
in induced state whereas the mesenchymal markers were found to be downregulated
in naive state and upregulated in induced state. Thus, our study concludes that
quercetin may prevent prostate cancer metastasis by regulating the components of
Wnt pathway.
PMID- 27495234
TI - Developments in the practice of physician-assisted dying: perceptions of
physicians who had experience with complex cases.
AB - BACKGROUND: Since the enactment of the euthanasia law in the Netherlands, there
has been a lively public debate on assisted dying that may influence the way
patients talk about euthanasia and physician-assisted suicide (EAS) with their
physicians and the way physicians experience the practice of EAS. AIM: To show
what developments physicians see in practice and how they perceive the influence
of the public debate on the practice of EAS. METHODS: We conducted a secondary
analysis of in-depth interviews with 28 Dutch physicians who had experience with
a complex case of EAS. Respondents were recruited both by the network of
physicians working for SCEN (Support and Consultation for Euthanasia in the
Netherlands) as well as via a national questionnaire, wherein participating
physicians could indicate their willingness to be interviewed. RESULTS: Three
themes came up in analysing the interviews. First, the interviewed physicians
experienced a change in what (family of) patients would expect from them: from a
role as an involved caregiver to being the mere performer of EAS. Second,
interviewees said that requests for EAS based on non-medical reasons came up more
frequently and wondered if EAS was the right solution for these requests. Last,
respondents had the impression that the standards of EAS are shifting and that
the boundaries of the EAS regulation were stretched. CONCLUSIONS: The perceived
developments could make physicians less willing to consider a request for EAS.
Our results also raise questions about the role of physicians and of EAS in
society.
PMID- 27495235
TI - Individual responsibility as ground for priority setting in shared decision
making.
AB - INTRODUCTION: Given healthcare resource constraints, voices are being raised to
hold patients responsible for their health choices. In parallel, there is a
growing trend towards shared decision-making, aiming to empower patients and give
them more control over healthcare decisions. More power and control over
decisions is usually taken to mean more responsibility for them. The trend of
shared decision-making would therefore seem to strengthen the case for invoking
individual responsibility in the healthcare priority setting. OBJECTIVE: To
analyse whether the implementation of shared decision-making would strengthen the
argument for invoking individual responsibility in the healthcare priority
setting using normative analysis. RESULTS AND CONCLUSIONS: Shared decision-making
does not constitute an independent argument in favour of employing individual
responsibility since these notions rest on different underlying values. However,
if a health system employs shared decision-making, individual responsibility may
be used to limit resource implications of accommodating patient preferences
outside professional standards and goals. If a healthcare system employs
individual responsibility, high level dynamic shared decision-making implying a
joint deliberation resulting in a decision where both parties are willing to
revise initial standpoints may disarm common objections to the applicability of
individual responsibility by virtue of making patients more likely to exercise
adequate control of their own actions. However, if communication strategies
applied in the shared decision-making are misaligned to the patient's initial
capacities, arguments against individual responsibility might, on the other hand,
gain strength.
PMID- 27495233
TI - MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell
survival and proliferation.
AB - The role of microRNAs (miRNAs) in glioma biology is increasingly recognized. To
investigate the regulatory mechanisms governing the malignant signature of
gliomas with different grades of malignancy, we analyzed miRNA expression
profiles in human grade I-IV tumor samples and primary glioma cell cultures.
Multiplex real-time PCR was used to profile miRNA expression in a set of World
Health Organization (WHO) grade I (pilocytic astrocytoma), II (diffuse fibrillary
astrocytoma), and IV (glioblastoma multiforme) astrocytic tumors and primary
glioma cell cultures. Primary glioma cell cultures were used to evaluate the
effect of transfection of specific miRNAs and miRNA inhibitors. miRNA microarray
showed that a set of miRNAs was consistently upregulated in all glioma samples.
miR-363 was upregulated in all tumor specimens and cell lines, and its expression
correlated with tumor grading. The transfection of glioma cells with the specific
inhibitor of miR-363 increased the expression level of tumor suppressor growth
associated protein 43 (GAP-43). Transfection of miR-363 induced cell survival,
while inhibition of miR-363 significantly reduced glioma cell viability.
Furthermore, miRNA-363 inhibition induced the downregulation of AKT, cyclin-D1,
matrix metalloproteinase (MMP)-2, MMP-9, and Bcl-2 and upregulation of caspase 3.
Together, these data suggest that the upregulation of miR-363 may play a role in
malignant glioma signature.
PMID- 27495236
TI - Are the current notification criteria for Lyme borreliosis in Norway suitable?
Results of an evaluation of Lyme borreliosis surveillance in Norway, 1995-2013.
AB - BACKGROUND: The approach to surveillance of Lyme borreliosis varies between
countries, depending on the purpose of the surveillance system and the
notification criteria used, which prevents direct comparison of national data. In
Norway, Lyme borreliosis is notifiable to the Surveillance System for
Communicable Diseases (MSIS). The current notification criteria include a
combination of clinical and laboratory results for borrelia infection (excluding
Erythema migrans) but there are indications that these criteria are not followed
consistently by clinicians and by laboratories. Therefore, an evaluation of Lyme
borreliosis surveillance in Norway was conducted to describe the purpose of the
system and to assess the suitability of the current notification criteria in
order to identify areas for improvement. METHODS: The CDC Guidelines for
Evaluation of Surveillance Systems were used to develop the assessment of the
data quality, representativeness and acceptability of MSIS for surveillance of
Lyme borreliosis. Data quality was assessed through a review of data from 1996 to
2013 in MSIS and a linkage of MSIS data from 2008 to 2012 with data from the
Norwegian Patient Registry (NPR). Representativeness and acceptability were
assessed through a survey sent to 23 diagnostic laboratories. RESULTS:
Completeness of key variables for cases reported to MSIS was high, except for
geographical location of exposureThe NPR-MSIS linkage identified 1047 cases in
both registries, while 363 were only reported to MSIS and 3914 were only recorded
in NPR. A higher proportion of cases found in both registries were recorded as
neuroborreliosis in MSIS (84.4 %) than those cases found only in MSIS (20.1 %).
The trend (average yearly increase or decrease in reported cases) of
neuroborreliosis in MSIS was not significantly different from the trend for all
other clinical manifestations recorded in MSIS in negative binomial regression (p
= 0.3). The 16 surveyed laboratories (response proportion 70 %) indicated
differences in testing practices and low acceptability of the notification
criteria. CONCLUSIONS: Given the challenges associated with diagnosing Lyme
borreliosis, the selected notification criteria should be closely linked with the
purpose of the surveillance system. Restricting reportable Lyme borreliosis to
neuroborreliosis may increase validity, while a more sensitive case definition
(potentially including erythema migrans) may better reflect the true burden of
disease. We recommend revising the current notification criteria in Norway to
ensure that they are unambiguous for clinicians and laboratories.
PMID- 27495237
TI - Clinical outcomes associated with albuminuria in central Australia: a cohort
study.
AB - BACKGROUND: Chronic kidney disease (CKD) and end-stage-kidney disease (ESKD)
continue to be under-diagnosed and a major burden for Aboriginal communities in
central Australia. The aim of this study was to examine the risk of poor clinical
outcomes associated with elevated albumin-to-creatinine ratio (ACR) among
Aboriginal people in central Australia. METHODS: Cox proportional hazards models
were used to estimate the risk of end stage kidney disease (ESKD), dialysis, CVD
(cardiovascular disease) and mortality associated with participants' baseline
albuminuria reading from a 10-year cohort study of Aboriginal people (n = 623)
from three communities in central Australia. Predictors of progression of
albuminuria were also examined in the context of the Kidney Health Australia
(KHA) Risk Matrix. RESULTS: A baseline ACR level of >=3.5 mg/mmol was associated
with an almost 10-fold increased risk of ESKD (95%CI 2.07-43.8) and a 15-fold
risk of dialysis (95%CI 1.89-121). Albuminuria >=3.5 mg/mmol was also associated
with a borderline 63 % increased risk of CVD (95%CI 0.98-2.71). No significant
association was observed with mortality from all-causes or chronic disease.
Diabetes and a waist-to-hip ratio >=0.90 independently predicted a two-fold
increased risk of a progression to higher ACR levels. CONCLUSIONS: A single
measure of moderately increased albuminuria was a strong predictor of renal
failure in this population. A single spot urine ACR analysis in conjunction with
the KHA Risk Matrix may be a useful and efficient strategy to screen for risk of
CKD and progression to dialysis in remote communities. A focus on individuals
with diabetes and/or central obesity for strategies to avoid increases in
albuminuria may also prevent future CKD and CVD complications.
PMID- 27495239
TI - Geoffrey James Roberts.
PMID- 27495238
TI - Recombinant production of medium- to large-sized peptides in Escherichia coli
using a cleavable self-aggregating tag.
AB - BACKGROUND: Peptides have recently become attractive for therapeutic
applications. However, efficient production of medium- to large-sized peptides
(30-100 amino acids [aa]) remains challenging both by recombinant and chemical
synthesis. We previously reported the formation of active enzyme aggregates in
Escherichia coli cells induced by the short beta-structured peptide ELK16
(LELELKLKLELELKLK) and developed a streamlined protein expression and
purification approach. In this approach, a cleavable self-aggregating tag (cSAT)
consisting of an intein molecule and ELK16 was used to release the recombinant
peptides with reasonable purity from active aggregates. RESULTS: In this work, we
extended the cSAT approach to a generalized expression and purification solution
for a set of medium- to large-sized peptides with important therapeutic uses,
including human glucagon-like peptide 1 (31 aa), B-type natriuretic peptide (32
aa), exendin 4 (39 aa), chemokine (C-C motif) ligand 5 (also known as RANTES, 66
aa), stromal cell-derived factor 1alpha (67 aa), insulin-like growth factor 1 (70
aa), and leptin (146 aa). After intein-mediated cleavage, the soluble peptides
were released directly into the supernatant while insoluble peptides could be
refolded and purified by reverse phase high-performance liquid chromatography.
Additionally, an N-terminal thioredoxin tag was added upstream of the target
peptides, which can be removed by enterokinase cleavage, generating native N
terminus for target peptides. Final yields of the peptides ranged from 0.1 to 1.8
MUg/mg wet cell weight at laboratory scale. CONCLUSIONS: The approach described
in this study provides a fast and efficient route to express and purify peptides
that are difficult or expensive to produce by chemical synthesis or by ordinary
recombinant methods. It is particularly well suited for large peptides, peptides
likely to be degraded, and peptides that have toxic effects on the host. It can
greatly reduce the cost and time of downstream processing, and thus may be useful
for both industrial manufacture and laboratory applications.
PMID- 27495240
TI - Long-term antibiotic exposure in soil is associated with changes in microbial
community structure and prevalence of class 1 integrons.
AB - Antimicrobial resistance is one of the most significant challenges facing the
global medical community and can be attributed to the use and misuse of
antibiotics. This includes use as growth promoters or for prophylaxis and
treatment of bacterial infection in intensively farmed livestock from where
antibiotics can enter the environment as residues in manure. We characterised the
impact of the long-term application of a mixture of veterinary antibiotics alone
(tylosin, sulfamethazine and chlortetracycline) on class 1 integron prevalence
and soil microbiota composition. Class 1 integron prevalence increased
significantly (P < 0.005) from 0.006% in control samples to 0.064% in the treated
plots. Soil microbiota was analysed using 16S rRNA gene sequencing and revealed
significant alterations in composition. Of the 19 significantly different (P <
0.05) OTUs identified, 16 were of the Class Proteobacteria and these decreased in
abundance relative to the control plots. Only one OTU, of the Class
Cyanobacteria, was shown to increase in abundance significantly; a curiosity
given the established sensitivity of this class to antibiotics. We hypothesise
that the overrepresentation of Proteobacteria as OTUs that decreased
significantly in relative abundance, coupled with the observations of an increase
in integron prevalence, may represent a strong selective pressure on these taxa.
PMID- 27495241
TI - Patterns of bacterial biodiversity in the glacial meltwater streams of the
McMurdo Dry Valleys, Antarctica.
AB - Microbial consortia dominate glacial meltwater streams from polar regions,
including the McMurdo Dry Valleys (MDV), where they thrive under physiologically
stressful conditions. In this study, we examined microbial mat types and
sediments found in 12 hydrologically diverse streams to describe the community
diversity and composition within and across sites. Sequencing of the 16S rRNA
gene from 129 samples revealed ~24 000 operational taxonomic units (<97% DNA
similarity), making streams the most biodiverse habitat in the MDV. Principal
coordinate analyses revealed significant but weak clustering by mat type across
all streams (ANOSIM R-statistic = 0.28) but stronger clustering within streams
(ANOSIM R-statistic from 0.28 to 0.94). Significant relationships (P < 0.05) were
found between bacterial diversity and mat ash-free dry mass, suggesting that
diversity is related to the hydrologic regimes of the various streams, which are
predictive of mat biomass. However, correlations between stream chemistry and
community members were weak, possibly reflecting the importance of internal
processes and hydrologic conditions. Collectively, these results suggest that
localized conditions dictate bacterial community composition of the same mat
types and sediments from different streams, and while MDV streams are hotspots of
biodiversity in an otherwise depauperate landscape, controls on community
structure are complex and site specific.
PMID- 27495242
TI - Genetic and ecophysiological traits of Synechococcus strains isolated from
coastal and open ocean waters of the Arabian Sea.
AB - The picocyanobacterium Synechococcus is a prominent primary producer in the
marine environment. The marine Synechococcus strains are clustered into different
clades representing ecologically distinct genotypes. In this study, we compared
phylogeny, photophysiology and cell cycles of four novel phycoerythrin-containing
Synechococcus strains (clade II of subcluster 5.1) isolated from different depths
of the water column (surface and subsurface waters) in coastal and offshore
regions of the eastern Arabian Sea. The surface water strains possessed a lesser
number of thylakoid layers and had a higher zeaxanthin to chlorophyll a ratio
than subsurface strains indicating possible influence of light intensity
available at their niche. The DNA distribution pattern of the four strains was
bimodal in optimal cellular physiology conditions with cell division restricted
to the light period and synchronized with the light-dark cycle. The presence of
phycourobilin or phycoerythrobilin and the ratio between these two chromophores
in all four strains varied according to available spectral wavelength in situ
This study indicates that the timing of cell division is conserved within these
genotypically identical Synechococcus strains, despite their having different
chromophore ratios. We conclude that the timing of cell division of the
Synechococcus strains has a genetic basis rather than being determined by
phenotypic characters, such as chromophore content and ratio.
PMID- 27495243
TI - Editorial: Special thematic issue on microbe-assisted crop production.
PMID- 27495244
TI - Chemotaxis and adherence to fungal surfaces are key components of the behavioral
response of Burkholderia terrae BS001 to two selected soil fungi.
AB - Burkholderia terrae BS001 has previously been proposed to be a 'generalist'
associate of soil fungi, but its strategies of interaction have been largely
ignored. Here, we studied the chemotactic behavior of B. terrae BS001 towards
Lyophyllum sp. strain Karsten and Trichoderma asperellum 302 and the role of
fungal surface molecules in their physical interaction with the bacteria. To
assess the involvement of the type 3 secretion system (T3SS), wild-type strain
BS001 and T3SS mutant strain BS001-DeltasctD were used in the experiments. First,
the two fungi showed divergent behavior when confronted with B. terrae BS001 on
soil extract agar medium. Lyophyllum sp. strain Karsten revealed slow growth
towards the bacterium, whereas T. asperellum 302 grew avidly over it. Both on
soil extract and M9 agar, B. terrae BS001 and BS001-DeltasctD moved
chemotactically towards the hyphae of both fungi, with a stronger response to
Lyophyllum sp. strain Karsten than to T. asperellum 302. The presence of a
progressively increasing glycerol level in the M9 agar enhanced the level of
movement. Different oxalic acid concentrations exerted varied effects, with a
significantly raised chemotactic response at lower, and a subdued response at
higher concentrations. Testing of the adherence of B. terrae BS001 and BS001
DeltasctD to Lyophyllum sp. strain Karsten and to cell envelope-extracted
ceramide monohexosides (CMHs) revealed that CMHs in both conidia and hyphae could
bind strain BS001 cells. As BS001-DeltasctD adhered significantly less to the
CMHs than BS001, the T3SS was presumed to have a role in the interaction. In
contrast, such avid adherence was not detected with T. asperellum 302. Thus, B.
terrae BS001 shows a behavior characterized by swimming towards Lyophyllum sp.
strain Karsten and T. asperellum 302 and attachment to the CMH moiety in the cell
envelope, in particular of the former.
PMID- 27495245
TI - Warfarin with sulfonylureas and hypoglycemic events: consider dose, length of
treatment, and all sulfonylureas.
PMID- 27495246
TI - Heart failure due to cytomegalovirus myocarditis in immunocompetent young adults:
a case report.
AB - BACKGROUND: Cardiac complications constitute a rare clinical manifestation of
cytomegalovirus (CMV) infection. This virus is usually asymptomatic in
immunocompetent individuals. We report a case of myocarditis and cardiac
insufficiency due to primary CMV infection. Serological tests by using ELISA
method showed positive results for the virus. CASE PRESENTATION: A 41-year-old
man with no prior comorbidities presenting with dyspnoea, fever, and oedema was
admitted to the cardiac emergency service. He had fever and dry cough, which
aggravated into progressive respiratory distress, lower limb oedema, and
orthopnoea 30 days prior to hospitalisation. The electrocardiogram revealed sinus
tachycardia, first-degree right bundle branch block, and ventricular and left
atrial overload as well as diffuse and nonspecific disturbances of ventricular
repolarization. Serological tests were conducted, and IgM (1.54 UI/mL) and IgG
(2.5 UI/mL) were found positive only for CMV by using ELISA. The patient was
diagnosed with cardiac insufficiency due to CMV myocarditis. He was treated with
ganciclovir for 10 days and received supportive medication. CONCLUSION: This case
reaffirms the possibility of cardiac involvement in CMV infection and emphasises
the importance of viral aetiologies as differential diagnoses for acute
myocarditis.
PMID- 27495248
TI - Carbon monoxide poisoning cases presenting with non-specific symptoms.
AB - Carbon monoxide (CO) is a colourless and odourless gas appearing as a result of
incomplete combustion of carbon-containing fuels. Many domestic or occupational
poisonings are caused by CO exposure. Malfunctioning heating systems, improperly
ventilated motor vehicles, generators, grills, stoves and residential fires may
be listed in the common sources of CO exposure. The aim of this study was to
emphasize the significance of early diagnosis of CO poisoning with non-invasive
measurement of CO levels of the patients with non-specific symptoms using a pulse
oximeter device in the triage. Our study was a cross-sectional study. Patients
who presented to the emergency department (ED) due to non-specific symptoms and
had a Canadian Triage and Acuity scale level of 4 or 5 were included in the
study; 106 (5.9%) of 1788 patients admitted during the study period were
diagnosed with CO poisoning. Patients with CO poisoning and the other patients
had statistically significant differences in terms of presenting symptoms,
namely, headache, dizziness, nausea, and vomiting. More CO poisoning cases were
admitted in the fall and winter compared to the spring and summer. The number of
CO poisoning victims can be decreased if preventive measures like CO monitoring
systems and well-designed ventilation systems are generalized at homes and
workplaces. Measurement of carboxyhaemoglobin levels of patients presenting to ED
due to non-specific symptoms like headache and dizziness during cold seasons and
winter months using a pulse CO-oximeter should be a part of the routine of
emergency medicine triage.
PMID- 27495247
TI - Association of diabetes and diabetes treatment with the host response in
critically ill sepsis patients.
AB - BACKGROUND: Diabetes is associated with chronic inflammation and activation of
the vascular endothelium and the coagulation system, which in a more acute manner
are also observed in sepsis. Insulin and metformin exert immune modulatory
effects. In this study, we aimed to determine the association of diabetes and
preadmission insulin and metformin use with sepsis outcome and host response.
METHODS: We evaluated 1104 patients with sepsis, admitted to the intensive care
unit and stratified according to the presence or absence of diabetes mellitus.
The host response was examined by a targeted approach (by measuring 15 plasma
biomarkers reflective of pathways implicated in sepsis pathogenesis) and an
unbiased approach (by analyzing whole genome expression profiles in blood
leukocytes). RESULTS: Diabetes mellitus was not associated with differences in
sepsis presentation or mortality up to 90 days after admission. Plasma biomarker
measurements revealed signs of systemic inflammation, and strong endothelial and
coagulation activation in patients with sepsis, none of which were altered in
those with diabetes. Patients with and without diabetes mellitus, who had sepsis
demonstrated similar transcriptional alterations, comprising 74 % of the
expressed gene content and involving over-expression of genes associated with pro
inflammatory, anti-inflammatory, Toll-like receptor and metabolic signaling
pathways and under-expression of genes associated with T cell signaling pathways.
Amongst patients with diabetes mellitus and sepsis, preadmission treatment with
insulin or metformin was not associated with an altered sepsis outcome or host
response. CONCLUSIONS: Neither diabetes mellitus nor preadmission insulin or
metformin use are associated with altered disease presentation, outcome or host
response in patients with sepsis requiring intensive care.
PMID- 27495249
TI - Carbon monoxide exposure among police officers working in a traffic dense region
of Southern India.
AB - Currently, in India, air pollution is widespread in urban areas where vehicles
are major contributors. The aim of this study was to investigate the level of
exposure in traffic police officers exposed to vehicle exhaust for less than 8
h/day. The specific objective of the study was to determine the levels of
carboxyhaemoglobin (COHb) in these officers. The effect of exposure for 8 h/day
is known, but shorter durations of chronic exposure need to be investigated, and
there is a need to explore the policy options in this exposed population. This
cross-sectional study, included non-smoking traffic police officers between 30
and 50 years of age working for more than 2 years in busy traffic junctions. The
cases were sex matched with controls of same age group, working in offices at a
teaching hospital. Venous blood was collected at the end of 3 h of duty for
estimation of COHb among both the groups. The COHb levels were expressed as
percentage values. Differences between the COHb levels among the traffic police
officers and office workers were analysed using the Mann-Whitney U test and
considered significant at p < 0.05. Traffic police officers had significantly
elevated COHb levels compared with the controls; 76.5% of traffic police officers
had COHb >2.5% compared with no office workers at this level and 41.2% of the
police officers had COHb levels >4%. Overall, 53.8% of officers with COHb >2.5%
reported headaches compared with 15.8% of officers with COHb <2.5%.
PMID- 27495250
TI - MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer,
and tumor growth associated with down-regulation of sec23a expression.
AB - BACKGROUND: MicroRNA-21 (miR-21) is up-regulated in many cancers, including
colorectal cancer (CRC). Nevertheless, the function of miR-21 in CRC and the
mechanism underlying that function is still unclear. METHODS: After analyzing the
expression of miR-21 and Sec23A in CRC cell lines, we transfected the highest miR
21 expressing cell line, SW-480, with a plasmid containing an miR-21 inhibitor
and the lowest miR-21 expressing cell line, DLD-1, with a plasmid containing an
miR-21 mimic and measured the effects on the expression of Sec23A and on cell
proliferation, migration, and invasion. We also evaluated the effect of knocking
down Sec23A on miR-21 expression and its effects on cell proliferation,
migration, and invasion. Finally, we assessed the effect of miR-21 in a xenograft
tumor model in mice. Tumor tissues from these mice were subjected to
immunohistochemical staining to detect the expression of Sec23A. RESULTS: Genetic
deletion of miR-21 suppressed the proliferation, migration, and invasion of SW
480 cells, while over-expression of miR-21 promoted proliferation, migration, and
invasion of DLD-1 cells. Inhibition of miR-21 increased the expression of Sec23A
protein in SW-480 cells while over-expression of miR-21 significantly suppressed
the expression of Sec23A protein and Sec23A mRNA in DLD-1 cells. Knockdown of
Sec23A increased the expression of miR-21 in SW480 and DLD-1 cells and their
proliferation (DLD-1 only), migration, and invasion. Over-expression of miR-21
promoted tumor growth in BALB/c nude mice and suppressed tumor expression of
Sec23A. CONCLUSION: These findings provide novel insight into the molecular
functions of miR-21 in CRC, which may serve as a potential interesting target.
PMID- 27495251
TI - Annual ambient atmospheric mercury speciation measurement from Longjing, a rural
site in Taiwan.
AB - The main purpose of this study was to monitor ambient air particulates and
mercury species [RGM, Hg(p), GEM and total mercury] concentrations and dry
depositions over rural area at Longjing in central Taiwan during October 2014 to
September 2015. In addition, passive air sampler and knife-edge surrogate surface
samplers were used to collect the ambient air mercury species concentrations and
dry depositions, respectively, in this study. Moreover, direct mercury analyzer
was directly used to detect the mercury Hg(p) and RGM concentrations. The result
indicated that: (1) The average highest RGM, Hg(p), GEM and total mercury
concentrations, and dry depositions were observed in January, prevailing dust
storm occurred in winter season was the possible major reason responsible for the
above findings. (2) The highest average RGM, Hg(p), GEM and total mercury
concentrations, dry depositions and velocities were occurred in winter. This is
because that China is the largest atmospheric mercury (Hg) emitter in the world.
Its Hg emissions and environmental impacts need to be evaluated. (3) The results
indicated that the total mercury ratios of Kaohsiung to that of this study were
5.61. This is because that Kaohsiung has the largest industry density (~60 %) in
Taiwan. (4) the USA showed average lower mercury species concentrations when
compared to those of the other world countries. The average ratios of China/USA
values were 89, 76 and 160 for total mercury, RGM and Hg(p), respectively, during
the years of 2000-2012.
PMID- 27495252
TI - Cultural events - does attendance improve health? Evidence from a Polish
longitudinal study.
AB - BACKGROUND: Although there is strong advocacy for uptake of both the arts and
creative activities as determinants of individual health conditions, studies
evaluating causal influence of attendance at cultural events on population health
using individual population data on health are scarce. If available, results are
often only of an associative nature. In this light, this study investigated
causative impact of attendance at cultural events on self-reported and physical
health in the Polish population. METHODS: Four recent waves (2009, 2011, 2013 and
2015) of the biennial longitudinal Polish household panel study, Social
Diagnosis, were analysed. The data, representative for the Polish population aged
over 16, with respect to age, gender, classes of place of residence and NUTS 2
regions, were collected from self-report questionnaires. Causative influence of
cultural attendance on population health was established using longitudinal
population representative data. To account for unobserved heterogeneity of
individuals and to mitigate issues caused by omitted variables, a panel data
model with a fixed effects estimator was applied. The endogeneity problem (those
who enjoy good health are more likely to participate in cultural activities more
frequently) was circumvented by application of instrumental variables. RESULTS:
Results confirmed positive association between cultural attendance and self
reported health. However, in contrast to the often suggested positive causative
relationship, such a link was not confirmed by the study. Additionally, no
evidence was found to corroborate a positive impact from cultural attendance on
physical health. Both findings were substantiated by augmentation in the
longitudinal perspective and causal link. CONCLUSIONS: We showed the relation
between attendance at cultural events and self-reported health could only be
confirmed as associational. Therefore, this study provided little justification
to encourage use of passive cultural participation as a measure of health
promotion (improvement). Our study did not confirm any identifiable benefit to
physical health from passive participation in culture. Future research should
investigate the causative influence of active participation in creative
activities on health outcomes as, in contrast to passive attendance, it may be
influential.
PMID- 27495253
TI - An assessment of outcomes with intramedullary fixation of fractured ribs.
AB - BACKGROUND: Surgical management of fractured ribs with internal fixation is an
increasingly accepted therapy. Concurrently, specific rib fixation prostheses are
being developed which should improve results and minimise hardware and rib/splint
construct failures. The Synthes titanium intramedullary splint lends itself to
difficult to access areas such as posterior rib fractures and fractures under the
scapula. We analyse a case series of patients in whom this rib fixation
prosthesis has been used. METHODS: Fifteen patients received 35 intramedullary
splints. Follow up at 3 and 6 months was performed with three dimensional
computed tomography scanning to assess for bone alignment, callus formation and
healing, residual deformity, hardware failure or cut through. Computerized finite
element analysis (FEA) was used to model forces acting on a posterior fracture
with and without an intramedullary fixation splint in situ. RESULTS: Complete
healing (bony union) was noted in only 3 (9 %) of the fractures fixed with
splints by 3 months. Partial healing (cartilaginous union) was noted in 28 of the
33 fractures (85 %), and non healing was noted in only 2 (6 %). In both those two
patients, failure at the rib / splint interface was noted after both patients
reported sneezing. No hardware failures were noted. By 6 months the fractures
which had shown partial healing, had all completely healed. There were no late
failures (between 3 and 6 months) of either hardware or rib/splint interfaces.
FEA modelling identified sites of increased stress in the rib at the rib / splint
interface and in a modelled intramedullary splint where it spans the fracture.
CONCLUSIONS: Further analysis of outcomes with intramedullary splints is
warranted as well as further development of intramedullary rib fixation
solutions.
PMID- 27495254
TI - Genome wide characterization of simple sequence repeats in watermelon genome and
their application in comparative mapping and genetic diversity analysis.
AB - BACKGROUND: Microsatellite markers are one of the most informative and versatile
DNA-based markers used in plant genetic research, but their development has
traditionally been difficult and costly. The whole genome sequencing with next
generation sequencing (NGS) technologies provides large amounts of sequence data
to develop numerous microsatellite markers at whole genome scale. SSR markers
have great advantage in cross-species comparisons and allow investigation of
karyotype and genome evolution through highly efficient computation approaches
such as in silico PCR. Here we described genome wide development and
characterization of SSR markers in the watermelon (Citrullus lanatus) genome,
which were then use in comparative analysis with two other important crop species
in the Cucurbitaceae family: cucumber (Cucumis sativus L.) and melon (Cucumis
melo L.). We further applied these markers in evaluating the genetic diversity
and population structure in watermelon germplasm collections. RESULTS: A total of
39,523 microsatellite loci were identified from the watermelon draft genome with
an overall density of 111 SSRs/Mbp, and 32,869 SSR primers were designed with
suitable flanking sequences. The dinucleotide SSRs were the most common type
representing 34.09 % of the total SSR loci and the AT-rich motifs were the most
abundant in all nucleotide repeat types. In silico PCR analysis identified 832
and 925 SSR markers with each having a single amplicon in the cucumber and melon
draft genome, respectively. Comparative analysis with these cross-species SSR
markers revealed complicated mosaic patterns of syntenic blocks among the genomes
of three species. In addition, genetic diversity analysis of 134 watermelon
accessions with 32 highly informative SSR loci placed these lines into two groups
with all accessions of C.lanatus var. citorides and three accessions of C.
colocynthis clustered in one group and all accessions of C. lanatus var. lanatus
and the remaining accessions of C. colocynthis clustered in another group.
Furthermore, structure analysis was consistent with the dendrogram indicating the
134 watermelon accessions were classified into two populations. CONCLUSION: The
large number of genome wide SSR markers developed herein from the watermelon
genome provides a valuable resource for genetic map construction, QTL
exploration, map-based gene cloning and marker-assisted selection in watermelon
which has a very narrow genetic base and extremely low polymorphism among
cultivated lines. Furthermore, the cross-species transferable SSR markers
identified herein should also have practical uses in many applications in species
of Cucurbitaceae family whose whole genome sequences are not yet available.
PMID- 27495256
TI - Pneumatosis intestinalis after gefitinib therapy for pulmonary adenocarcinoma: a
case report.
AB - BACKGROUND: Pneumatosis intestinalis (PI) is defined as the presence of gas in
the bowel wall and is a relatively rare finding. PI has been associated with
various pathological conditions and medications. Although several
chemotherapeutic agents and molecular targeted therapy agents are reported to be
associated with PI, there have been few reports describing the association
between the anti-epidermal growth factor receptor agent gefitinib, a tyrosine
kinase inhibitor (TKI), and PI. The present report describes a case of PI
secondary to gefitinib therapy. CASE PRESENTATION: An 80-year-old woman who had
been diagnosed with recurrent lung adenocarcinoma presented with remarkable
appetite loss, abdominal distension, and constipation after starting gefitinib
therapy. A computed tomography (CT) scan of the abdomen revealed PI extending
from the small intestine to the rectum. The patient was managed conservatively,
and gefitinib therapy was discontinued. Subsequently, the symptoms improved and a
follow-up abdominal X-ray showed a reduction in intramural air. After gefitinib
was restarted, PI occurred three more times. CONCLUSIONS: Although PI is
extremely rare, physicians should be aware of the risk of PI in patients
undergoing gefitinib therapy.
PMID- 27495255
TI - Response of Hepatic Stellate Cells to TGFB1 Differs from the Response of
Myofibroblasts. Decorin Protects against the Action of Growth Factor.
AB - Regardless to the exact nature of damage, hepatic stellate cells (HSCs) and other
non-parenchymal liver cells transform to activated myofibroblasts, synthesizing
the accumulating extracellular matrix (ECM) proteins, and transforming growth
factor-beta1 (TGF-beta1) plays a crucial role in this process. Later it was
discovered that decorin, member of the small leucin rich proteoglycan family is
able to inhibit this action of TGF-beta1. The aim of our present study was to
clarify whether HSCs and activated myofibroblasts of portal region exert
identical or different response to TGF-beta1 exposure, and the inhibitory action
of decorin against the growth factor is a generalized phenomenon on myofibroblast
of different origin? To this end we measured mRNA expression and production of
major collagen components (collagen type I, III and IV) of the liver after
stimulation and co-stimulation with TGF-beta1 and decorin in primary cell
cultures of HSCs and myofibroblasts (MFs). Production of matrix proteins, decorin
and members of the TGF-beta1 signaling pathways were assessed on Western blots.
Messenger RNA expression of collagens and TIEG was quantified by real-time RT
PCR. HSCs and MFs responded differently to TGF-beta1 exposure. In contrast to
HSCs in which TGF-beta1 stimulated the synthesis of collagen type I, type III,
and type IV, only the increase of collagen type IV was detected in portal MFs.
However, in a combined treatment, decorin seemed to interfere with TGF-beta1 and
its stimulatory effect was abolished. The different mode of TGF-beta1 action is
mirrored by the different activation of signaling pathways in activated HSCs and
portal fibroblasts. In HSCs the activation of pSMAD2 whereas in myofibroblasts
the activation of MAPK pathway was detected. The inhibitory effect of decorin was
neither related to the Smad-dependent nor to the Smad-independent signaling
pathways.
PMID- 27495257
TI - Relationship between frailty, physical performance and quality of life among
nursing home residents: the SENIOR cohort.
AB - BACKGROUND: The aim of this study was to assess the relationship between frailty
and a large number of indicators related to physical and muscular performance as
well as quality of life. METHODS: This is an analysis of data collected at
baseline in the Sample of Elderly Nursing home Individuals: an Observational
Research (SENIOR) cohort including nursing home residents. Subjects are
volunteer, oriented and able to walk (walking assistance allowed) nursing home
residents in Belgium. A large number of demographic and clinical characteristics,
including physical and muscular performance, were collected from each patient.
The prevalence of frailty in this population was assessed using Fried's
definition. RESULTS: In total, 662 subjects are included in this analysis. The
mean age of the sample is 83.2 +/- 8.99 years, and 484 (73.1 %) are women. In
this population of nursing home residents, the prevalence of frailty is 25.1 %,
pre-frailty, 59.8 % and robustness, 15.1 %. Compared to non-frail subjects, frail
subjects have lower physical and muscular performances and a lower quality of
life. CONCLUSION: Frailty, according to Fried's definition, seems to be
associated with several clinical indicators suggesting a higher level of
disability and an increased propensity to develop major clinical consequences.
Follow-up data of the SENIOR cohort will be helpful in confirming these findings,
establishing cause-effect relationships and identifying the most predictive
components of physical frailty for adverse outcomes in nursing homes.
PMID- 27495258
TI - Utilization of long-term care after decompressive hemicraniectomy for severe
stroke among older patients.
AB - BACKGROUND: While clinical trial data support decompressive hemicraniectomy (DHC)
as improving survival among patients with severe ischemic stroke, quality of life
outcomes among older persons remain controversial. AIMS: To aid decision-making
and understand practice variation, we measured long-term outcomes and patterns of
regional variation for a nationwide cohort of ischemic stroke patients after DHC.
METHODS: Medicare fee-for-service ischemic stroke cases over age 65 during the
year 2008 were used to create a cohort followed for 2 years (2009-2010) after
stroke and DHC procedure. Rates of mortality, acute hospital readmission, and
long-term care (LTC) utilization were calculated. Multiple logistic regression
was used to identify individual predictors of institutional LTC. Regional
variation in DHC was calculated through aggregation and merging with the state
level data. RESULTS: Among 397,503 acute ischemic stroke patients, 130 (0.03 %)
underwent DHC. Mean age was 72 years, and 75 % were between the ages of 65 and
74. Mortality was highest (38 %) within the first 30 days. At 2 years, 59 % of
the original cohort had died. The 30-day rate of acute hospital readmission was
25 %. Among survivors, 75 % returned home 1 year after index stroke admission.
States with higher per capita health expenditures were associated with wider
variation in utilization of DHC. CONCLUSIONS: There is a high rate of mortality
among older stroke patients undergoing DHC. Although most survivors of DHC are
not permanently institutionalized, there is wide variation in utilization of DHC
across the USA.
PMID- 27495259
TI - Aesthetic Plastic Surgery Checklist: A Safety Tool.
AB - INTRODUCTION: About one in ten patients experiences iatrogenic events, and more
than half of these occur in the perioperative environment. The objective of this
study was to develop a complete and functional checklist for aesthetic plastic
surgery and test it in patients who would undergo elective plastic surgeries.
METHODS: Patient data were collected from a general hospital and the particular
clinic between October 2013 and October 2015, through history, physical
examination, diagnosis, laboratory tests, pre-, during, and postoperatively, and
complications. An expanded safety checklist was developed and optimized for
aesthetic plastic surgery based on the model presented by the WHO in 2009 with
reference to the information related to the prevention of more frequent
complications in this specialty. RESULTS: The tool was applied to 486 patients,
of whom 430 (88 %) were women and 56 (12 %) were men. The most frequently
performed procedure was liposuction with 30 % of cases, and the most widely used
type of anesthesia (39 %) was local anesthesia + sedation. The greater adherence
of professionals to the checklist was the group of residents (98 %). The observed
complications were seromas (7 %), other complications unrelated to the wound (3
%), and hematoma (0.2 %) in only one patient who underwent facelift. CONCLUSION:
The use of the checklist in addition to allowing data collection and the
identification of potential risks promoted favorable changes in the attitudes of
some professionals and generated interest in patient safety and teamwork. LEVEL
OF EVIDENCE IV: This journal requires that the 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- 27495260
TI - Adverse Events of Botulinum Toxin Type A in Facial Rejuvenation: A Systematic
Review and Meta-Analysis.
AB - BACKGROUND: Botulinum toxin A (BTX-A) is a medical product that is used widely in
cosmetics, and concern over the safety profile has increased among injectors and
patients. OBJECTIVE: The purpose was to enhance the statistical effect size using
a meta-analysis to detect the incidence rate of adverse events (AEs) in the
treatment of facial wrinkles. METHODS: A systematic search was performed for
randomized, double-blind, placebo-controlled trials published through July 2015.
RESULTS: We searched 16 trials, including 42,405 individual participants, and
found that in all enrolled facial rejuvenation studies, patients in the BTX-A
group had significantly more AEs than those patients in the placebo group (RR =
1.24; 95 % CI 1.07-1.43; p = 0.003). For crow's feet lines injection analysis,
the BTX-A group did not exhibit any significant increase in AEs compared with the
control group (RR = 1.19; 95 % CI 0.96-1.48; p = 0.12), except in injection site
hematoma (RR = 2.14; 95 % CI 1.13-4.07; p = 0.02) in the treatment group. For
frown wrinkle injection analysis, AEs were significantly observed in the BTX-A
group (RR = 1.47; 95 % CI 1.23-1.77; p < 0.0001), particularly headaches (RR =
1.53; 95 % CI 1.15-2.03; p = 0.003), eyelid ptosis (RR = 5.56; 95 % CI 1.68
18.38; p = 0.005), and heavy eyelids (RR = 6.94; 95 % CI 1.27-37.93; p = 0.03).
CONCLUSION: This meta-analysis confirmed the safety profile of BTX-A for
glabellar and crow's feet lines, and BTX-A usage for the removal of upper facial
wrinkles, which have some significant mild-to-moderate adverse profiles,
including headache, eye disorder, eyelid ptosis, and heavy eyelids. Facial
injectors should abide by the technical standards of neurotoxic drugs and be
familiar with the local pharmacological effects to lessen the severe side
effects. LEVEL OF EVIDENCE I: 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 A5 online
Instructions to Authors www.springer.com/00266 .
PMID- 27495261
TI - The Aesthetically Ideal Position of the Nipple-Areola Complex on the Breast.
AB - BACKGROUND: Several studies have attempted to identify an objective description
of the aesthetically ideal breast, but they have all suffered in their
reliability because of having several intrinsic limitations. It is therefore
essential to design a template of ideal breast features in order to predict and
evaluate aesthetic outcomes in both reconstructive and cosmetic breast surgery.
The aim of this study was to determine the aesthetically preferred position of
the nipple-areola complex on the breast. METHODS: A questionnaire was sent by
regular mail to 1000 men and 1000 women aged between 16 and 74 years. They were
asked to rank the attractiveness of a series of breasts of women in images with
different NAC positions. The images showed breasts from two different angles: 12
frontal-view images with both breasts shown, and five side-view images with only
one breast shown. All of the breasts had equal dimensions and proportions, with
the same areola size but different NAC positions. Statistical analysis of data
was carried out. RESULTS: Eight hundred and thirteen of 2000 participants
completed the questionnaire. The NAC placement preferred by both genders had a
ratio of 40:60 x and 50:50 y, which means that it was best situated in the middle
of the breast gland vertically and slightly lateral to the midpoint horizontally.
Significant differences were found between the age and gender subgroup
preferences. CONCLUSIONS: This study identified the preferred position of the
nipple-areola complex on the female breast in the general population. This is an
important information when planning breast reconstructive and cosmetic surgery.
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- 27495262
TI - Performance of real-world functional vision tasks by blind subjects improves
after implantation with the Argus(r) II retinal prosthesis system.
AB - BACKGROUND: The main objective of this study was to test Argus II subjects on
three real-world functional vision tasks. DESIGN: The study was designed to be
randomized and prospective. Testing was conducted in a hospital/research
laboratory setting at the various participating centres. PARTICIPANTS: Twenty
eight Argus II subjects, all profoundly blind, participated in this study.
METHODS: Subjects were tested on the three real-world functional vision tasks:
Sock Sorting, Sidewalk Tracking and Walking Direction Discrimination task MAIN
OUTCOME MEASURES: For the Sock Sorting task, percentage correct was computed
based on how accurately subjects sorted the piles on a cloth-covered table and on
a bare table. In the Sidewalk Tracking task, an 'out of bounds' count was
recorded, signifying how often the subject veered away from the test course.
During the Walking Direction Discrimination task, subjects were tested on the
number of times they correctly identified the direction of testers walking across
their field of view. RESULTS: The mean percentage correct OFF versus ON for the
Sock Sorting task was found to be significantly different for both testing
conditions (t-test, P < 0.01). On the Sidewalk Tracking task, subjects performed
significantly better with the system ON than they did with the system OFF (t
test, P < 0.05). Eighteen (18) of 27 subjects (67%) performed above chance with
the system ON, and 6 (22%) did so with system OFF on the Walking Direction
Discrimination task. CONCLUSIONS: Argus II subjects performed better on all three
tasks with their systems ON than they did with their systems OFF.
PMID- 27495263
TI - Antibacterial, anti-biofilm and anticancer potentials of green synthesized silver
nanoparticles using benzoin gum (Styrax benzoin) extract.
AB - This study described a simple and green approach for the synthesis of silver
nanoparticles (AgNPs) employing benzoin gum water extract as a reducing and
capping agent and their applications. The AgNPs were characterized by ultraviolet
visible spectrophotometer, X-ray diffraction pattern, field emission transmission
electron microscopy, dynamic light scattering, zeta potential and fourier
transform infrared spectroscopy. The AgNPs showed promising antimicrobial
activity against various pathogens (Gram-negative, Gram-positive and fungus) and
possessed high free radical scavenging activity (104.5 +/- 7.21 % at 1 mg/ml). In
addition, the AgNPs exhibited strong cytotoxicity towards human cervical cancer
and human lung cancer cells as compared to the normal mouse macrophage cells.
Moreover, the AgNPs possessed anti-biofilm activity against Escherichia coli, and
compatibility to human keratinocyte HaCaT cells, which suggests the use of
dressing with the AgNPs in chronic wound treatment. Therefore, AgNPs synthesized
by benzoin gum extract are comparatively green and may have broad spectrum
potential application in biomedicine.
PMID- 27495264
TI - Corneal endothelial cell loss after Baerveldt glaucoma drainage device
implantation in the anterior chamber.
AB - PURPOSE: To investigate central and peripheral corneal endothelial cell density
(ECD) in relation to Baerveldt (BV) glaucoma drainage device (GDD) tube corneal
(TC) distance. METHODS: Prospective study of all patients scheduled for glaucoma
tube surgery with 36 months follow-up. A BV GDD was inserted into the anterior
chamber (AC). Anterior segment optical coherence tomography (AS-OCT) scans were
made to determine the TC distance. Central and peripheral ECD was measured,
preoperatively and at 3, 6, 12, 24 and 36 months postoperatively. RESULTS: Fifty
three eyes were included [primary open-angle glaucoma, (n = 13); secondary
glaucoma, (n = 30); and primary angle-closure glaucoma, (n = 10)]. Central ECD
significantly decreased during follow-up, with a mean decrease of 4.54% per year
(p < 0.001), and 6.57% in the peripheral quadrant closest to the BV GDD tube
(PQC, p < 0.001). In the PQC, a yearly decrease of 1.57% was shown after
transiridial tube placement versus 7.43% after placement 'free' into the AC (p =
0.006). Endothelial cell (EC) loss was related to TC distance (mean 1.69 mm),
with a central loss of 6.20% and 7.25% in the PQC per year with shorter TC
distances, versus a central loss of 4.11% and 5.77% in the PQC per year with
longer TC distances (outside mean +/- 2SD, p < 0.001). A difference in EC loss by
glaucoma subtype was not identified. CONCLUSION: The TC distance is of
significant influence on corneal ECD, a shorter TC distance causing more severe
EC loss, especially in the PQC. Transiridial placement of the BV GDD tube seems
safer than placement 'free' into the AC.
PMID- 27495265
TI - Paronychia-like digital metastases of osteosarcoma.
PMID- 27495266
TI - Imaging and quantification of iron-oxide nanoparticles (IONP) using MP-RAGE and
UTE based sequences.
AB - PURPOSE: To investigate two-dimensional (2D) and three-dimensional (3D)
ultrashort echo time (UTE) and 3D magnetization-prepared rapid gradient-echo (MP
RAGE) sequences for the imaging of iron-oxide nanoparticles (IONP). METHODS: The
phantoms were composed of tubes filled with different IONP concentrations ranging
from 2 to 45 mM. The tubes were fixed in an agarose gel phantom (0.9% by weight).
Morphological imaging was performed with 3D MP-RAGE, 2D UTE, 2D adiabatic
inversion recovery-prepared UTE (2D IR-UTE), 3D UTE with Cones trajectory (3D
Cones), and 3D IR-Cones sequences. Quantitative assessment of IONP concentration
was performed using R2*(1/T2*) and R1 (1/T1 ) measurements using a 3 Tesla (T)
scanner. RESULTS: The 3D MP-RAGE sequence provides high-contrast images of IONP
with concentration up to 7.5 mM. Higher IONP concentration up to 37.5 mM can be
detected with the UTE sequences, with the highest IONP contrast provided by the
3D IR-Cones sequence. A linear relationship was observed between R2* and IONP
concentration up to ~45 mM, and between R1 and IONP concentration up to ~30 mM.
CONCLUSION: The clinical 3D MP-RAGE sequence can be used to assess lower IONP
concentration up to 7.5 mM. The UTE sequences can be used to assess higher IONP
concentration up to 45 mM. Magn Reson Med 78:226-232, 2017. (c) 2016
International Society for Magnetic Resonance in Medicine.
PMID- 27495268
TI - Clinically atypical nevi following diode laser therapy.
PMID- 27495267
TI - TDP-43 pathology in Alzheimer's disease, dementia with Lewy bodies and ageing.
AB - Intracellular inclusions consisting of TAR DNA binding protein-43 (TDP-43
pathology) are present in up to 57% of Alzheimer's disease (AD) cases and follow
a distinct topographical pattern of progression described in the TDP-43 in AD
staging scheme. This scheme has not been applied to the assessment of TDP-43
pathology in dementia with Lewy bodies (DLB) and aged controls. We investigated
TDP-43 pathology prevalence and severity in AD, DLB, mixed AD/DLB (Mx AD/DLB) and
aged controls. One hundred and nineteen human post-mortem brains were included,
neuropathologically diagnosed as AD: 46, DLB: 15, Mx AD/DLB: 19 and aged
controls: 39. Paraffin sections inclusive of the amygdala, hippocampus, striatum
and neocortex were immunohistochemically stained with antibodies against
phosphorylated TDP-43 and staged according to the TDP-43 in AD staging scheme.
TDP-43 pathology was present in all groups: AD: 73.9%, DLB: 33.3%, Mx AD/DLB:
52.6% and controls: 17.9%. Prevalence of TDP-43 pathology was significantly
higher in AD and Mx AD/DLB compared to controls. In controls, higher age at death
was associated with prevalence of TDP-43 pathology and higher TDP-43 in AD stage,
suggesting that this type of TDP-43 pathology may partly be an age-associated
phenomenon. Significantly higher prevalence of TDP-43 pathology in the AD group
indicates that AD pathology possibly triggers and aggravates TDP-43 pathology.
The validity of the TDP-43 in AD staging scheme is not limited to AD and should
be applied to assess TDP-43 pathology in post mortem brains of aged individuals
to further elucidate the role of TDP-43 pathology in age associated
neurodegeneration.
PMID- 27495270
TI - Students' perceptions of pre-clinical endodontic training with artificial teeth
compared to extracted human teeth.
AB - PURPOSE: Artificial teeth have several advantages in pre-clinical endodontics
training. This study aimed to compare artificial resin teeth with extracted human
teeth, from a student's perspective, during a pre-clinical undergraduate
endodontic course for three consecutive academic years (2011-2014). METHODS: At
the end of the course, students completed a questionnaire that included questions
about their perceptions of the difficulty of artificial teeth vs. natural teeth
and ranked the perceived advantages of artificial teeth. RESULTS: Participants
expressed that all procedures, except obturation, were more difficult to perform
on artificial teeth than on natural teeth, a result that was due to the hardness
of the resin. They ranked the fairness and availability as the best advantages.
CONCLUSION: Artificial teeth have multiple advantages but cannot replace natural
teeth. The physical characteristics through the manufacturing material of
artificial teeth should be enhanced to increase wider use and acceptance.
PMID- 27495269
TI - Effects of infrared laser moxibustion on cancer-related fatigue: A randomized,
double-blind, placebo-controlled trial.
AB - BACKGROUND: Fatigue is the most common symptom negatively affecting the quality
of life of patients with cancer. The objective of the current study was to
evaluate the preliminary efficacy and safety of 10.6-MUm infrared laser
moxibustion for cancer-related fatigue (CRF). METHODS: The authors conducted a
randomized, placebo-controlled trial among 78 patients with cancer who were
diagnosed with CRF. The group treated with infrared laser moxibustion received
10.6 MUm of infrared laser moxibustion on the ST36 (bilateral), CV4, and CV6
acupoints. Each participant received a 20-minute treatment session 3 times per
week for 4 weeks. The sham group received the same treatment duration on the same
acupoints, but without infrared laser output. The outcome was change in fatigue
as measured by the Chinese version of the Brief Fatigue Inventory between groups
at week 4 with additional evaluation at week 8 for durability of treatment
effects. A mixed effects model was used to evaluate the difference in treatment
effect over time. RESULTS: Among those randomized, 61 patients (78%) completed
the entire study. At the end of the intervention, the individuals in the group
treated with the laser were found to have significantly less fatigue than those
in the sham group (3.01 vs 4.40; P = .002). The improvement in fatigue persisted
to week 8, favoring the group treated with laser moxibustion (3.03 vs 4.26; P =
.006). Laser moxibustion was safe, with 3 cases of mild local erythema that
resolved without medical intervention reported. CONCLUSIONS: Infrared laser
moxibustion appeared to be safe and efficacious for improving CRF in a Chinese
patient population. Larger studies in more racial/ethnically diverse populations
are needed to confirm the benefit of this technique for fatigue in patients with
cancer. Cancer 2016;122:3667-72. (c) 2016 The Authors. Cancer published by Wiley
Periodicals, Inc. on behalf of American Cancer Society. This is an open access
article under the terms of the Creative Commons Attribution-NonCommercial
License, which permits use, distribution and reproduction in any medium, provided
the original work is properly cited and is not used for commercial purposes.
PMID- 27495271
TI - In vivo periodontal tissue regeneration by periodontal ligament stem cells and
endothelial cells in three-dimensional cell sheet constructs.
AB - BACKGROUND AND OBJECTIVE: Chronic periodontitis causes damage to tooth-supporting
tissues, resulting in tooth loss in adults. Recently, cell-sheet-based approaches
have been studied to overcome the limitations of conventional cytotherapeutic
procedures for periodontal regeneration. The purpose of the present study was to
investigate the regenerative potential of periodontal ligament stem cells
(PDLSCs) and human umbilical vein endothelial cells (HUVECs) in three-dimensional
(3D) cell sheet constructs for periodontal regeneration in vivo. MATERIAL AND
METHODS: PDLSCs, HUVECs or co-cultures of both cells were seeded onto temperature
responsive culture dishes, and intact cell sheets were fabricated. Cell sheets
were wrapped around the prepared human roots in three different combinations and
implanted subcutaneously into immunodeficient mice. RESULTS: Histological
evaluation revealed that after 2, 4 and 8 wk of implantation, periodontal
ligament-like tissue arrangements were observed around the implanted roots in
experimental groups compared with controls. Vascular lumens were also observed in
periodontal compartments of HUVEC-containing groups. Periodontal ligament
regeneration, cementogenesis and osteogenesis were evident in the experimental
groups at both weeks 4 and 8, as shown by immunostaining for periostin and bone
sialoprotein. Human cells in the transplanted cell sheets were stained by
immunohistochemistry for the presence of human mitochondria. CONCLUSIONS: The 3D
cell sheet-based approach may be potentially beneficial and is thus encouraged
for future regenerative periodontal therapy.
PMID- 27495272
TI - Monitoring children's health and well-being by indicators and index: apples and
oranges or fruit salad?
AB - The use of indicators is a fast and widely spread way to monitor groups of
children's health and well-being. Indicators are useful in research; but they are
also important tools for planners and politicians. Although they are constructed
to simplify reality, in many reports they still offer a complex and confusing
picture, not least by their sheer numbers. Although they are constructed to
simplify reality, in many reports, they still offer a complex and confusing
picture, not least by their sheer numbers. Therefore, there is an increasing
demand for even further simplifications, where the indicators are combined into
single summary numbers, composite indices. At the same time, as a composite index
summarizes a complex and sometimes elusive process, making it more accessible for
advocacy and political interventions, the combining of very dissimilar components
makes the results difficult to interpret and use. There is an obvious dilemma
between the need for rigour and evidence, the research orientation, and the wish
for a simple and summarizing overview of the findings, the policy orientation.
Models have been created to form indicator sets, either by combining them by
simple addition or by weighting them or by just leaving them as separate
indicators. Most index systems in operation use an equal weighting system after
standardization, once the components have been selected. Examples of these models
are described as well as their pros and cons, and a summary of suitable ways of
handling the problems of indicators and composite indices is offered. Some
surveys have taken the best from different approaches, presenting the results as
a summary index for the great picture, as subindices for the various domains of
child health and as separate indicators for the detailed study of the basic
components. A Swedish Child Health Index is presented as an example of such a
solution.
PMID- 27495273
TI - Latin American protected areas: Protected from chemical pollution?
AB - Protected areas (PAs) are critically important means to preserve species and
maintain natural ecosystems. However, the potential impacts of chemical pollution
on PAs are seldom mentioned in the scientific literature. Research on the extent
of the occurrence of chemical pollution inside PAs and in-depth assessments of
how chemical contaminants may adversely affect the maintenance of species
abundance, species survival, and ecosystem functions are scarce to nonexistent.
We investigated 1) the occurrence of chemical contaminants inside 119 PAs in
Latin America from publically available databases, and 2) reviewed case studies
of chemical contaminants and pollution in 4 Latin American PAs. Cases of chemical
pollution and contamination inside Latin American PAs mostly originated from
sources such as mining, oil, and gas extraction. To date, the focus of the
research on chemical pollution research inside Latin American PAs has been
primarily on the detection of contamination, typically limited to trace metals.
Where management actions have occurred, they have been reactive rather than
proactive. Protected areas established in wetlands are the most affected by
chemical pollution. Based on the information from the pollution and/or
contamination occurrence and the case studies analyzed, Latin American PAs are
not well safeguarded from chemical pollution, resulting in both challenges and
opportunities to conserve biodiversity and ecosystems. Integr Environ Assess
Manag 2017;13:360-370. (c) 2016 SETAC.
PMID- 27495274
TI - Measurement equivalence of the Consumer Assessment of Healthcare Providers and
Systems (CAHPS(r)) Medicare survey items between Whites and Asians.
AB - PURPOSE: Asians report worse experiences with care than Whites. This could be due
to true differences in care received, expectations about care, or survey response
styles. We examined responses to the Consumer Assessment of Healthcare Providers
and Systems (CAHPS(r)) Medicare survey items by Whites and Asians, controlling
for underlying level on the CAHPS constructs. METHODS: We conducted multiple
group analyses to evaluate measurement equivalence of CAHPS Medicare survey data
between White and Asian Medicare beneficiaries for CAHPS reporting composites
(communication with personal doctor, access to care, plan customer service) and
global ratings of care using pooled data from 2007 to 2011. Responses were
obtained from 1,326,410 non-Hispanic Whites and 40,672 non-Hispanic Asians
(hereafter referred to as Whites and Asians). The median age for Whites was 70,
with 24 % 80 or older, and 70 for Asians, with 23 % 80 or older. Fifty-eight
percent of Whites and 56 % of Asians were female. RESULTS: A model without group
specific estimates fit the data as well as a model that included 12 group
specific estimates (7 factor loadings, 3 measured variable errors, and 2 item
intercepts): Comparative Fit Index = 0.947 and 0.948; root-mean-square error of
approximation = 0.052 and 0.052, respectively). Differences in latent CAHPS score
means between Whites and Hispanics estimated from the two models were similar,
differing by 0.053 SD or less. CONCLUSIONS: This study provides support for
measurement equivalence of the CAHPS Medicare survey composites (communication,
access, customer service) and global ratings between White and Asian respondents,
supporting comparisons of care experiences between the two groups.
PMID- 27495275
TI - Mortality risk and perceived quality of life as a function of waking time in
discretionary movement-based behaviors: isotemporal substitution effects.
AB - OBJECTIVE: Previous research has examined associations of sedentary behavior
(SB), light-intensity physical activity (LIPA) and moderate-to-vigorous physical
activity (MVPA) with health-related quality of life (HRQOL) and mortality.
However, most of these studies have been limited to examining their potential
"independent" effects, as opposed to whether mortality risk and HRQOL vary as a
function of waking time in these discretionary movement-related behaviors, which
was this study's purpose. METHODS: Data from the 2003-2006 NHANES were employed,
with follow-up mortality assessed through 2011 (5377 adults 20-85 years). HRQOL
was assessed via survey, with physical activity assessed using an accelerometer
over a 7-day monitoring period. Isotemporal substitution analyses were employed.
RESULTS: Participants engaged in little MVPA during their monitored waking time
and higher mortality risk appeared to cluster more so among those spending a
greater proportion of their day in SB with less LIPA engagement. Substituting 30
min/day of SB with MVPA would be expected to reduce mortality risk by 81 %
(HRadjusted = 0.19; 95 % CI: 0.06-0.60; P = 0.006) and reduce worse HRQOL by 72 %
(OR = 0.28; 95 % CI: 0.13-0.58; P = 0.001). CONCLUSIONS: Allocation of waking
time in movement-based behaviors is associated with all-cause mortality and
HRQOL. Thus, clinicians should encourage their patients to substitute SB with
reasonable amounts of LIPA and MVPA.
PMID- 27495276
TI - Predicting urinary incontinence after surgery for pelvic organ prolapse.
AB - PURPOSE OF REVIEW: Many women choosing to have surgery for pelvic organ prolapse
also choose to undergo continence surgery. This review focuses on available
evidence that clinicians may use to counsel patients when choosing whether to
perform continence surgery and how predictive analytic tools improve this
decision-making process. RECENT FINDINGS: Midurethral sling, Burch
cystourethropexy and bladder neck sling are highly effective for the surgical
treatment of stress urinary incontinence. Trials demonstrate that continence
surgery may be routinely performed to reduce the risk of postoperative
incontinence in women undergoing surgery for pelvic organ prolapse with or
without preoperative stress urinary incontinence. Although these procedures are
effective and well tolerated on average, media concerns, regulatory warnings and
litigation reinforce the need for a balanced discussion regarding efficacy and
potential adverse events directed at the individual patient during the
preoperative visit. Advances in predictive analytics allow surgeons to quantitate
individual risk using algorithms that tailor estimates for the individual patient
and facilitate shared understanding of risks and benefits. These models are less
prone to cognitive biases and frequently outperform experienced clinicians.
SUMMARY: This review discusses how predictive analytic tools can be used to
improve decisions about continence surgery in the woman planning to undergo
prolapse surgery.
PMID- 27495277
TI - Erratum to: Sex Disparity in Gastric Cancer: Female Sex is a Poor Prognostic
Factor for Advanced Gastric Cancer.
PMID- 27495278
TI - Lymph Node Ratio Is Less Prognostic in Melanoma When Minimum Node Retrieval
Thresholds Are Not Met.
AB - BACKGROUND: Lymph node ratio (LNR), positive nodes divided by nodes examined, has
been proposed for prognostication in melanoma to mitigate problems with low node
counts. However, it is unclear if LNR offers superior prognostication over total
counts of positive nodes and nodes examined. Additionally, the prognostic value
of LNR may change if a threshold number of nodes are examined. We evaluated
whether LNR is more prognostic than positive nodes and nodes examined, and
whether the prognostic value of LNR changes with minimum thresholds. METHODS:
Using the National Cancer Data Base Participant User File, we identified 74,692
incident cases with nodal dissection during 2000-2006. We compared LNR versus
counts of examined and positive nodes based on Harrell's C, a measure of
predictive ability. We then stratified by total nodes examined: greater versus
fewer than ten for axillary lymph node dissection (ALND) and greater versus fewer
than five for inguinal lymph node dissection (ILND). RESULTS: Overall, LNR had a
Harrell's C of 0.628 (95 % confidence interval [CI] 0.625-0.631). Examined and
positive nodes were not significantly different from this, with a Harrell's C of
0.625 (95 % CI 0.621-0.630). In ALND, LNR had a Harrell's C of 0.626 (95 % CI
0.610-0.643) with >=10 nodes versus 0.554 (95 % CI 0.551-0.558) < 10 nodes. In
ILND, LNR had a Harrell's C of 0.679 (95 % CI 0.664-0.694) with >=5 nodes versus
C of 0.601 (95 % CI 0.595-0.606) < 5 nodes. CONCLUSIONS: LNR provides no
prognostic superiority versus counts of examined and positive nodes. Moreover,
the prognostic value of LNR diminishes when minimum node retrieval thresholds are
not met.
PMID- 27495280
TI - Robotic-Assisted Placement of an Hepatic Artery Infusion Pump and Catheter for
Regional Chemotherapy of the Liver.
AB - BACKGROUND: Hepatic artery infusion (HAI) chemotherapy is an effective regional
therapy for unresectable colorectal liver metastases (U-CRLM).1 , 2 One of its
limitations is the need for a laparotomy, which can delay the use of systemic
therapy.3 Here, we describe a purely robotic technique for placement of an HAI
pump (Fig 1). PATIENT: A 62-year-old male presented with a symptomatic ascending
colon cancer and multiple bilobar unresectable liver metastases. He underwent
laparoscopic right colectomy followed by six cycles of FOLFOXIRI and bevacizumab
with stable disease by RECIST (Response Evaluation Criteria in Solid Tumors)
criteria, and also underwent robotic HAI pump placement. TECHNIQUE: The patient
was placed supine on a split-leg table, and four robotic and two laparoscopic
assistant ports were placed as shown. Use of the robot allowed for precise
dissection of the common hepatic artery (CHA) and gastroduodenal artery (GDA), as
well as a portal lymphadenectomy. A standard cholecystectomy was performed and
the GDA was dissected for a distance of 2-3 cm from its takeoff from the CHA. The
robotic scissors were used to create a precise transverse GDA arteriotomy, and
the HAI pump catheter tip was advanced to the CHA/GDA junction and secured with
two silk ties. Finally, a methylene blue dye injection test was performed to
ensure uniform distribution within the liver. Operative time was 147 min,
estimated blood loss was 20 ml, and the postoperative course was uneventful. The
first dose of HAI with floxuridine was administered on postoperative day 4 (day
of discharge) and systemic chemotherapy was administered 2 weeks later.
CONCLUSION: The robotic platform allows for minimally invasive HAI pump
placement. Fig. 1 Port placement for robotic-assisted hepatic artery infusion
pump placement using the DaVinci Si platform. Illustration depicts a 12 mm
periumbilical port for the robotic camera (upper green port), three 8 mm (purple)
robotic working ports (the left MCL, right MCL, and right AAL for robotic arms
R1, R2, and R3, respectively), and 12 mm (lower green) and 5 mm (red)
laparoscopic assistant ports in the right and left lower quadrants, respectively.
The pump pocket is created in the left lower quadrant just below the 5 mm (red)
port site.
PMID- 27495279
TI - Changing Odds of Survival Over Time among Patients Undergoing Surgical Resection
of Gallbladder Carcinoma.
AB - BACKGROUND: While survival after malignancies is traditionally reported as
actuarial survival, conditional survival (CS) may be more clinically relevant by
accounting for "accrued" survival time as time progresses. We sought to compare
actuarial and CS among patients with gallbladder carcinoma (GBC) . METHODS: A
total of 312 patients who underwent curative intent surgery for GBC between 2000
and 2014 were identified using a multi-institutional database. Overall survival
(OS) was estimated using the Kaplan-Meier method. CS was calculated as the
probability of surviving an additional 3 years at year "x" after surgery using
the formula CS3 = S(x+3)/Sx. RESULTS: Among all patients, the median actuarial OS
was 24.8 months (IQR 13.3-88.9). While actuarial survival decreased over time, 3
year CS (CS3) increased, with CS3 at 2 years after surgery noted to be 61.8 %
compared with the 5-year actuarial OS of 31.6 %. Factors associated with reduced
actuarial OS were positive margin status (HR 3.61, 95 % CI 2.47-5.26), increasing
tumor size (HR = 1.02, 95 % CI 1.01-1.02), higher tumor grade (HR 2.98, 95 % CI
1.47-6.04), residual disease at repeat resection (HR = 2.78, 95 % CI 1.49-3.49, p
< 0.001), and lymph node metastasis (HR = 1.95, 95 % CI 1.39-2.75, all p <
0.001). The calculated CS3 exceeded the actuarial survival within each high-risk
patient subgroup. For example, patients with residual disease at repeat resection
had an actuarial survival 23.1 % at 5 years versus a CS3 of 56.3 % in patients
alive at 2 years (Delta = 33.2 %). CONCLUSIONS: CS provides a more accurate,
dynamic estimate for survival, especially among high-risk patients. CS estimates
can be used to accurately predict survival and guide clinical decision making.
PMID- 27495281
TI - Laparoscopic Anterior Resection with Transvaginal Specimen Extraction (TVSE) for
Colorectal Cancer and Concomitant Total Hysterectomy and Bilateral Salpingo
Oophrectomy (THBSO): A Technical Description.
AB - BACKGROUND: Natural orifice specimen extraction (NOSE) has evolved to circumvent
the need for a specimen extraction site. Transvaginal specimen extraction (TVSE)
for colorectal disease has been shown to be safe and feasible in selected cases.1
, 2 We describe our technique of TVSE in a case of laparoscopic ultra-low
anterior resection (ULAR) with defunctioning ileostomy (DI) with a concomitant
total hysterectomy and bilateral salpingo-oophrectomy (THBSO). METHODS AND
RESULTS: A 74-year-old Chinese female was diagnosed with a mid-rectal cancer
following colonoscopic evaluation for a change in bowel habits. Preoperative
magnetic resonance imaging (MRI) suggested T2N0 disease and the patient was
recommended for upfront surgery following multidisciplinary discussion. Computed
tomography (CT) scan confirmed a 4.3 * 3.4 cm right adnexal cystic lesion,
without enhancing septations or soft tissue component. No metastatic disease was
identified. The patient underwent a laparoscopic ULAR with DI and THBSO with
TVSE; operative time was 469 min. The specimen showed a 2.5 cm mid-rectal tumour.
Histology revealed a pT3N1a moderately differentiated adenocarcinoma of the mid
rectum, with 1 of 20 lymph nodes involved by metastatic carcinoma. The quality of
the total mesorectal excision (TME) was good, with no breach in the mesorectal
fascia. The distal and radial margins were 1.5 and 3.0 cm, respectively. The
patient recovered well postoperatively, with minimal wound site pain, and was
discharged well on postoperative day 5. CONCLUSION: TVSE is oncologically safe
and feasible in certain malignant colorectal pathologies. It is an option to
consider in selected cases that require a concomitant gynecological procedure.
PMID- 27495282
TI - Distal Pancreatectomy with en Bloc Celiac Axis Resection (Modified Appleby
Procedure) for Locally Advanced Pancreatic Body Cancer: A Single-Center Review of
80 Consecutive Patients.
AB - BACKGROUND: Recently, distal pancreatectomy with en bloc celiac axis resection
(DP-CAR) or modified Appleby procedure for locally advanced pancreatic body
cancer is increasingly reported. However, actual long-term survival data are
still unknown. METHODS: This study retrospectively reviewed 80 consecutive
patients with pancreatic body cancer who underwent DP-CAR at a single
institution. RESULTS: The study included 40 men and 40 women with a median age of
65 years (range, 44-85 years). A pancreatic fistula was the most common
complication, occurring in 47 patients (57.5 %). Other complications with a high
incidence were ischemic gastropathy (23 patients, 28.8 %) and delayed gastric
emptying (20 patients, 25 %). According to the Clavien-Dindo classification, the
major complications, defined as complications of grade 3 or higher, were observed
in 33 patients (41.3 %), and the in-hospital mortality involved four patients (5
%). For all 80 patients, the 1-, 2-, and 5-year overall survivals (OSs) were
respectively 81.1, 56.9, and 32.7 %, and the median survival time was 30.9
months. The actual 5-year survival for the 61 patients whose surgery was
performed five or more years earlier was 27.9 % (17 of 61). The 1-, 2-, and 5
year OSs for the patients who underwent preoperative therapy (100, 90, and 78.8
%) were significantly better than for those who underwent upfront surgery (77.9,
51.5, and 26.7 %; P < 0.0001). CONCLUSIONS: The findings show DP-CAR to be a
valid procedure for treating locally advanced pancreatic body cancer, which might
contribute more to patients' survival when performed as part of multidisciplinary
treatment.
PMID- 27495283
TI - Evaluation and treatment of insomnia in adult cancer survivorship programs.
AB - PURPOSE: Insomnia is commonly experienced by cancer survivors. Chronic insomnia
is associated with significant physical and psychosocial consequences if not
properly treated. Both the National Cancer Institute (NCI) and the National
Comprehensive Cancer Network (NCCN) recommend the evaluation of sleep
disturbances and evidence-based treatment of insomnia during routine survivorship
care. To better understand current clinical practices, we conducted a survey of
major cancer centers across the United States (US). METHODS: Adult survivorship
programs at the 25 US cancer centers that are both NCI-designated comprehensive
cancer centers and NCCN member institutions were surveyed about the evaluation
and treatment of insomnia in their hospital. RESULTS: All institutions responded
to the survey. Thirteen centers (56 %) reported screening <25 % of survivors for
sleep disorders, and few clinicians providing survivorship care were well
prepared to conduct a proper sleep evaluation. Insomnia was most commonly treated
with sleep hygiene, or pharmacotherapy, rather than cognitive-behavioral therapy.
No program reported that >50 % of their survivors were receiving optimal insomnia
related care. A variety of methods to improve insomnia care were endorsed by
respondents. CONCLUSIONS: There is a clear need to improve the evaluation and
treatment of insomnia for cancer survivors at institutions across the country.
Cancer centers deemed a number of modalities relevant for improving provider
confidence in addressing sleep challenges. IMPLICATIONS FOR CANCER SURVIVORS: To
improve the quality of insomnia care for survivors, systematic interventions to
increase standardized screening for sleep disorders, providing additional sleep
medicine training for survivorship clinicians, and optimizing the role of sleep
medicine specialists in the oncology setting should be considered.
PMID- 27495284
TI - Suicide risk in primary care patients diagnosed with a personality disorder: a
nested case control study.
AB - BACKGROUND: Personality disorder (PD) is associated with elevated suicide risk,
but the level of risk in primary care settings is unknown. We assessed whether PD
among primary care patients is linked with a greater elevation in risk as
compared with other psychiatric diagnoses, and whether the association is
modified by gender, age, type of PD, and comorbid alcohol misuse. METHODS: Using
data from the UK Clinical Practice Research Datalink, 2384 suicides were matched
to 46,899 living controls by gender, age, and registered practice. Prevalence of
PD, other mental disorders, and alcohol misuse was calculated for cases and
controls separately and conditional logistic regression models were used to
estimate exposure odds ratios. We also fitted gender interaction terms and
formally tested their significance, and estimated gender age-specific effects.
RESULTS: We found a 20-fold increase in suicide risk for patients with PD versus
no recorded psychiatric disorder, and a four-fold increase versus all other
psychiatric illnesses combined. Borderline PD and PD with comorbid alcohol misuse
were associated with a 37- and 45-fold increased risk, respectively, compared
with those with no psychiatric disorders. Relative risks were higher for female
than for male patients with PD. Significant risks associated with PD diagnosis
were identified across all age ranges, although the greatest elevations were in
the younger age ranges, 16-39 years. CONCLUSIONS: The large elevation in suicide
risk among patients diagnosed with PD and comorbid alcohol misuse is a particular
concern. GPs have a potentially key role to play in intervening with patients
diagnosed with PD, particularly in the presence of comorbid alcohol misuse, which
may help reduce suicide risk. This would mean working with specialist care,
agreed clinical pathways and availability of services for comorbidities such as
alcohol misuse, as well as opportunities for GPs to develop specific clinical
skills.
PMID- 27495285
TI - Conformational Space and Stability of ETD Charge Reduction Products of Ubiquitin.
AB - Owing to its versatility, electron transfer dissociation (ETD) has become one of
the most commonly utilized fragmentation techniques in both native and non-native
top-down mass spectrometry. However, several competing reactions-primarily
different forms of charge reduction-occur under ETD conditions, as evidenced by
the distorted isotope patterns usually observed. In this work, we analyze these
isotope patterns to compare the stability of nondissociative electron transfer
(ETnoD) products, specifically noncovalent c/z fragment complexes, across a range
of ubiquitin conformational states. Using ion mobility, we find that more
extended states are more prone to fragment release. We obtain evidence that for a
given charge state, populations of ubiquitin ions formed either directly by
electrospray ionization or through collapse of more extended states upon charge
reduction, span a similar range of collision cross-sections. Products of gas
phase collapse are, however, less stabilized towards unfolding than the native
conformation, indicating that the ions retain a memory of previous conformational
states. Furthermore, this collapse of charge-reduced ions is promoted if the ions
are 'preheated' using collisional activation, with possible implications for the
kinetics of gas-phase compaction. Graphical Abstract ?.
PMID- 27495286
TI - Lipid Emulsion Formulation of Parenteral Nutrition Affects Intestinal Microbiota
and Host Responses in Neonatal Piglets.
AB - BACKGROUND: Total parenteral nutrition (TPN) is a cause of intestinal microbial
dysbiosis and impaired gut barrier function. This may contribute to life
threatening parenteral nutrition-associated liver disease and sepsis in infants.
We compared the effects of a lipid emulsion containing long-chain omega-3
polyunsaturated fatty acids (PUFAs; SMOFlipid) and a predominantly omega-6 PUFA
emulsion (Intralipid) on microbial composition and host response at the mucosal
surface. MATERIALS AND METHODS: Neonatal piglets were provided isocaloric,
isonitrogenous TPN for 14 days versus sow-fed (SF) controls. Equivalent lipid
doses (10 g/kg/d) were given of either SMOFlipid (ML; n = 10) or Intralipid (SO;
n = 9). Ileal segments and mucosal scrapings were used to characterize microbial
composition by 16S rRNA gene sequencing and quantitative gene expression of tight
junction proteins, mucins, antimicrobial peptides, and inflammatory cytokines.
RESULTS: The microbial composition of TPN piglets differed from SF, while ML and
SO differed from each other (analysis of molecular variance; P < .05); ML piglets
were more similar to SF, as indicated by UniFrac distance ( P < .05). SO piglets
showed a specific and dramatic increase in Parabacteroides ( P < .05), while ML
showed an increase in Enterobacteriaceae ( P < .05). Gene expression of mucin,
claudin 1, beta-defensin 2, and interleukin 8 were higher in TPN; overall
increases were significantly less in ML versus SO ( P < .05). CONCLUSION: The
formulation of parenteral lipid is associated with differences in the gut
microbiota and host response of TPN-fed neonatal piglets. Inclusion of omega-3
long-chain PUFAs appears to improve host-microbial interactions at the mucosal
surface, although mechanisms are yet to be defined.
PMID- 27495288
TI - Liquid biopsies will be routine NHS test for cancer "in under five years".
PMID- 27495287
TI - Effect of oral sodium bicarbonate on fibroblast growth factor-23 in patients with
chronic kidney disease: a pilot study.
AB - BACKGROUND: The regulation of fibroblast growth factor-23 (FGF23) secretion in
patients with chronic kidney disease (CKD) is incompletely understood. An in
vitro study showed that metabolic acidosis increased FGF23 in mouse bone. The
objective of this study is to evaluate the effect of oral sodium bicarbonate on
circulating FGF23 levels in patients with CKD. METHODS: This was a single-blind
pilot study. Twenty adults with estimated glomerular filtration rate between 15
45 mL/min/1.73 m(2) and serum bicarbonate between 20-24 mEq/L were treated with
placebo for 2 weeks, followed by increasing doses of oral sodium bicarbonate
(0.3, 0.6 and 1.0 mEq/kg/day) in 2 week intervals for a total of 6 weeks. C
terminal FGF23 levels were measured at the initial visit, after 2 weeks of
placebo and after 6 weeks of bicarbonate therapy. Wilcoxon matched-pairs signed
rank test was used to compare FGF23 before and after sodium bicarbonate. RESULTS:
After 6 weeks of oral sodium bicarbonate, the median FGF23 increased
significantly from 150.9 RU/mL (IQR 107.7-267.43) to 191.4 RU/mL (IQR 132.6
316.9) (p = 0.048) and this persisted after excluding participants who received
activated vitamin D. CONCLUSIONS: FGF23 increased after short-term oral sodium
bicarbonate therapy in patients with CKD and mild metabolic acidosis. It is
unclear whether this was due to the alkalinizing effect of sodium bicarbonate or
other factors. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov
( NCT00888290 ) on April 23, 2009.
PMID- 27495289
TI - In-Vitro dual inhibition of protein glycation, and oxidation by some Arabian
plants.
AB - BACKGROUND: Diabetes mellitus is a metabolic disorder of epidemic proportion,
projected to become the major cause of morbidity and mortality in the world in
future. Despite extensive research in understanding this disease at molecular
level, and the discovery of new drugs, diabetes and its complications remain
largely untreated. Many of the late diabetic complications are associated with
the glycation of proteins in the body. Natural flora has long been a rich source
for therapeutic agents, especially against diabetes. The present study deals with
the anti-glycation properties of some medicinally important plants of Arabian
region. METHODS: Twenty-six medicinal plants, commonly found in different regions
of Arabian Peninsula, were evaluated for their protein anti-glycation activity by
using BSA-MG glycation assay in-vitro. The extracts were incubated with BSA and
MG at 37 degrees C for 9 days, each sample was then examined for the presence of
fluorescence (lambdaex 330 nm, and lambdaem 420 nm), which represent the extent
of protein glycation. Antioxidant activity was evaluated by using 1,1-diphenyl- 2
picrylhydrazyl (DPPH), iron chelation, and superoxide radical scavenging asaays.
RESULTS: The data revealed that out of 26 medicinal plants, five plants viz. Sida
cordifolia, Plumbago zeylanica, Tribulus terrestris, Glycyrrhiza glabra, and Rosa
indica were active against the in-vitro protein glycation with IC50 values
between 0.408- 1.690 mg/mL. Among the active plants, Glycyrrhiza glabra L. was
found to be the most potent (IC50 = 0.408 +/- 0.027 mg/mL), followed by Rosa
indica (IC50 = 0.596 +/- 0.0179 mg/mL), and Sida cordifolia L. (IC50 = 0.63 +/-
0.009 mg/mL). The antioxidant potential of these plant extracts were also
determined by using DPPH (2,2-diphenyl-1-picrylhydrazyl), iron chelation, and
superoxide anion radical scavenging assays. Among five plants, Sida cordifolia
exhibited a potent anti-oxidant activity in both DPPH and superoxide anion
radical scavenging assays (IC50 = 0.005 +/- 0.0004, and 0.078 +/- 0.002 mg/mL,
respectively), followed by Rosa indica (IC50 = 0.023 +/- 0.0005 and 0.141 +/-
0.003 mg/mL, respectively). CONCLUSIONS: Protein glycation in hyperglycemic
conditions involve oxidative changes. Therefore dual inhibition of protein
glycation and oxidation are desirable properties in any test substance
investigated for therapeutic purposes.
PMID- 27495290
TI - Subjective evaluation of the frequency of coffee intake and relationship to
osteoporosis in Chinese men.
AB - BACKGROUND: The main purpose of this study was to evaluate the associations
between frequency of coffee intake and osteoporosis (OP) in a general Chinese
male sample. METHODS: We conducted a large-scale, community-based, cross
sectional study to investigate the associations by using a self-report
questionnaire to estimate the frequency of coffee intake. A total of 992 men were
available for data analysis in this study. Multiple regression models controlling
for confounding factors to include frequency of coffee intake variable were
performed to investigate the relationships for OP. RESULTS: Positive correlations
between frequency of coffee intake and T-score were reported (beta = 0.211, P =
0.024). Multiple regression analysis indicated that the frequency of coffee
intake was significantly associated with OP (P < 0.05 for model 1 and model 2).
The men with moderate frequency of coffee intake had a lower prevalence of OP.
CONCLUSIONS: The findings indicated that consumption of coffee was independently
and significantly associated with OP. The prevalence of OP was less frequent in
Chinese men with moderate coffee intake. TRIAL REGISTRATION: ClinicalTrials.gov,
NCT02451397.
PMID- 27495291
TI - A post-hoc analysis of the comparative efficacy of canagliflozin and glimepiride
in the attainment of type 2 diabetes-related quality measures.
AB - BACKGROUND: The randomized, double-blind CANTATA-SU (CANagliflozin Treatment And
Trial Analysis Sulfonyl Urea) clinical trial compared the use of canagliflozin
(100 mg or 300 mg) and maximally tolerated glimepiride (6-8 mg) over 104 weeks as
add-on therapy for patients with type 2 diabetes mellitus (T2DM) inadequately
controlled with metformin. Compared with glimepiride, canagliflozin use was
associated with durable reductions in glycated hemoglobin (A1C), blood pressure
(BP), and body weight. The aim of this post-hoc analysis of the CANTATA-SU trial
was to assess the comparative efficacy of canagliflozin and glimepiride in the
attainment of recently updated diabetes-related quality measures (QMs) for up to
104 weeks of treatment. METHODS: This post-hoc analysis evaluated the proportions
of patients achieving individual diabetes-related QMs using data from the
randomized, double-blind, Phase 3 CANTATA-SU trial. Change in A1C from baseline,
and proportions of the study population achieving QMs: A1C <7.0 %, <8.0 %, and
>9.0 % were assessed. Secondary endpoints included change in BP from baseline,
and the proportions of the study population achieving QMs related to BP and body
weight. RESULTS: The proportions of patients in the canagliflozin 100 mg,
canagliflozin 300 mg, and glimepiride groups meeting criteria for all QMs were
similar at baseline. At 52 and 104 weeks of treatment, canagliflozin 100 mg and
canagliflozin 300 mg provided better or similar reductions in A1C from baseline
and achievement of glycemic control QMs compared with glimepiride. At 52 and 104
weeks of treatment, the attainment of QMs related to reductions in body weight
and BP all favored canagliflozin compared with glimepiride. Canagliflozin was
associated with lower incidence of documented hypoglycemia and severe
hypoglycemia compared with glimepiride. CONCLUSIONS: Using the recently adjusted
and currently accepted diabetes-related QMs, this analysis observed superior
glycemic control with canagliflozin compared with maximally tolerated glimepiride
in patients with T2DM who were previously poorly controlled on metformin
monotherapy. Compared with maximally tolerated glimepiride, canagliflozin
resulted in better achievement of diabetes-related QMs related to weight loss and
BP, and was associated with lower incidences of hypoglycemic events. TRIAL
REGISTRATION: Clinical trial registry name: CANagliflozin Treatment And Trial
Analysis-Sulfonylurea (CANTATA-SU) SGLT2 Add-on to Metformin Versus Glimepiride.
CLINICAL TRIAL REGISTRATION NUMBER: NCT00968812 , registered August 28, 2009.
PMID- 27495292
TI - Stereoselective Metabolism of Bupropion to OH-bupropion, Threohydrobupropion,
Erythrohydrobupropion, and 4'-OH-bupropion in vitro.
AB - Bupropion is a widely used antidepressant, smoking cessation aid, and weight-loss
therapy. It is administered as a racemic mixture, but the pharmacokinetics and
activity of bupropion are stereoselective. The activity and side effects of
bupropion are attributed to bupropion and its metabolites S,S- and R,R-OH
bupropion, threohydrobupropion, and erythrohydrobupropion. Yet the
stereoselective metabolism in vitro and the enzymes contributing to the
stereoselective disposition of bupropion have not been characterized. In humans,
the fraction of bupropion metabolized (fm) to the CYP2B6 probe metabolite OH
bupropion is 5-16%, but ticlopidine increases bupropion exposure by 61%,
suggesting a 40% CYP2B6 and/or CYP2C19 fm for bupropion. Yet, the CYP2C19
contribution to bupropion clearance has not been defined, and the enzymes
contributing to overall bupropion metabolite formation have not been fully
characterized. The aim of this study was to characterize the stereoselective
metabolism of bupropion in vitro to explain the stereoselective pharmacokinetics
and the effect of drug-drug interactions (DDIs) and CYP2C19 pharmacogenetics on
bupropion exposure. The data predict that threohydrobupropion accounts for 50 and
82%, OH-bupropion for 34 and 12%, erythrohydrobupropion for 8 and 4%, and 4'-OH
bupropion for 8 and 2% of overall R- and S-bupropion clearance, respectively. The
fm,CYP2B6 was predicted to be 21%, and the fm,CYP2C19, 6% for racemic bupropion.
Importantly, ticlopidine was found to inhibit all metabolic pathways of bupropion
in vitro, including threohydrobupropion, erythrohydrobupropion, and 4'OH
bupropion formation, explaining the in vivo DDI. The stereoselective
pharmacokinetics of bupropion were quantitatively explained by the in vitro
metabolic clearances and in vivo interconversion between bupropion stereoisomers.
PMID- 27495293
TI - Absence of association between whole blood viscosity and delirium after cardiac
surgery: a case-controlled study.
AB - BACKGROUND: Delirium after cardiothoracic surgery is common and associated with
impaired outcomes. Although several mechanisms have been proposed (including
changes in cerebral perfusion), the pathophysiology of postoperative delirium
remains unclear. Blood viscosity is related to cerebral perfusion and thereby
might contribute to the development of delirium after cardiothoracic surgery. The
aim of this study was to investigate whether whole blood viscosity differs
between cardiothoracic surgery patients with and without delirium. METHODS: In
this observational study postoperative whole blood viscosity of patients that
developed delirium (cases) were compared with non-delirious cardiothoracic
surgery patients (controls). Cases were matched with the controls, yielding a 1:4
case-control study. Serial hematocrit, fibrinogen, and whole blood viscosity were
determined pre-operatively and at each postoperative day. Delirium was assessed
using the validated Confusion Assessment Method for the Intensive Care Unit or
Delirium Screening Observation scale. RESULTS: In total 80 cardiothoracic surgery
patients were screened of whom 12 delirious and 48 matched non-delirious patients
were included. No significant difference was found between both groups in
fibrinogen (p = 0.36), hematocrit (p = 0.23) and the area under curve of the
whole blood viscosity between shear rates 0.02 and 50 s(-1) (p = 0.80) or between
shear rates 0.02 and 5 s(-1) (p = 0.78). CONCLUSION: In this case control study
in cardiothoracic surgery patients changes in whole blood viscosity were not
associated with the development of delirium.
PMID- 27495294
TI - Outcomes of abdominoperineal resection for management of anal cancer in HIV
positive patients: a national case review.
AB - BACKGROUND: The incidence of anal cancer in human immunodeficiency virus (HIV)
positive individuals is increasing, and how co-infection affects outcomes is not
fully understood. This study sought to describe the current outcome disparities
between anal cancer patients with and without HIV undergoing abdominoperineal
resection (APR). METHODS: A retrospective review of all US patients diagnosed
with anal squamous cell carcinoma, undergoing an APR, was performed. Cases were
identified using a weighted derivative of the Healthcare Utilization Project's
National Inpatient Sample (2000-2011). Patients greater than 60 years old were
excluded after finding a skewed population distribution between those with and
without HIV infection. Multivariable logistic regression and generalized linear
modeling analysis examined factors associated with postoperative outcomes and
cost. Perioperative complications, in-hospital mortality, length of hospital
stay, and hospital costs were compared for those undergoing APR with and without
HIV infection. RESULTS: A total of 1725 patients diagnosed with anal squamous
cell cancer undergoing APR were identified, of whom 308 (17.9 %) were HIV
positive. HIV-positive patients were younger than HIV-negative patients
undergoing APR for anal cancer (median age 47 years old versus 51 years old, p <
0.001) and were more likely to be male (95.1 versus 30.6 %, p < 0.001).
Postoperative hemorrhage was more frequent in the HIV-positive group (5.1 versus
1.5 %, p = 0.05). Mortality was low in both groups (0 % in HIV-positive versus
1.49 % in HIV-negative, p = 0.355), and length of stay (LOS) (10+ days; 75th
percentile of patient data) was similar (36.9 % with HIV versus 29.8 % without
HIV, p = 0.262). Greater hospitalization costs were associated with patients who
experienced a complication. However, there was no difference in hospitalization
costs seen between HIV-positive and HIV-negative patients (p = 0.66).
CONCLUSIONS: HIV status is not associated with worse postoperative recovery after
APR for anal cancer as measured by length of stay or hospitalization cost.
Further study may support APRs to be used more aggressively in HIV-positive
patients with anal cancer.
PMID- 27495296
TI - Diagnosis and treatment based on quantitative PCR after controlled human malaria
infection.
AB - BACKGROUND: Controlled human malaria infection (CHMI) has become well-established
in the evaluation of drugs and vaccines. Anti-malarial treatment is usually
initiated when thick blood smears are positive by microscopy. This study explores
the effects of using the more sensitive qPCR as the primary diagnostic test.
METHODS: 1691 diagnostic blood samples were analysed by microscopy and qPCR from
115 volunteers (55 malaria naive and 60 having received chemoprophylaxis and
sporozoite immunization) who were challenged by five mosquitoes infected with
Plasmodium falciparum sporozoites of the NF54 strain. RESULTS: Retrospective
analysis of different qPCR criteria for diagnosis and treatment, showed that once
daily qPCR (threshold 100 parasites/ml) had 99 % sensitivity and 100 %
specificity, and shortened the median prepatent period from 10.5 to 7.0 days
after CHMI when compared to twice daily measurement of thick blood smears
(threshold 4000 parasites/ml). This is expected to result in a 78 % decrease of
adverse events before initiation of treatment in future studies. Trial outcome
related to infection and protective efficacy remained unchanged. CONCLUSION: The
use of qPCR as the primary diagnostic test in CHMI decreases symptoms as well as
parasitaemia while obviating the need for twice daily follow-up. The
implementation improves safety while reducing the clinical burden and costs
without compromising the evaluation of protective efficacy.
PMID- 27495295
TI - A community-based lifestyle and weight loss intervention promoting a
Mediterranean-style diet pattern evaluated in the stroke belt of North Carolina:
the Heart Healthy Lenoir Project.
AB - BACKGROUND: Because residents of the southeastern United States experience
disproportionally high rates of cardiovascular disease (CVD), it is important to
develop effective lifestyle interventions for this population. METHODS: The
primary objective was to develop and evaluate a dietary, physical activity (PA)
and weight loss intervention for residents of the southeastern US. The
intervention, given in eastern North Carolina, was evaluated in a 2 year
prospective cohort study with an embedded randomized controlled trial (RCT) of a
weight loss maintenance intervention. The intervention included: Phase I (months
1-6), 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/m(2) offered in 2 formats (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
RCT for those losing >= 8 lb with all other participants receiving a lifestyle
maintenance intervention. Change in diet and PA behaviors, CVD risk factors, and
weight were assessed at 6, 12, and 24 month follow-up. RESULTS: Baseline
characteristics (N = 339) were: 260 (77 %) females, 219 (65 %) African Americans,
mean age 56 years, and mean body mass index 36 kg/m(2). In Phase I, among 251 (74
%) that returned for 6 month follow-up, there were substantial improvements in
diet score (4.3 units [95 % CI 3.7 to 5.0]), walking (64 min/week [19 to 109]),
and systolic blood pressure (-6.4 mmHg [-8.7 to -4.1]) that were generally
maintained through 24 month follow-up. In Phase II, 138 (57 group only, 81
group/phone) chose the weight loss intervention and at 12 months, weight change
was: -3.1 kg (-4.9 to -1.3) for group (N = 50) and -2.1 kg (-3.2 to -1.0) for
group/phone combination (N = 75). In Phase III, 27 participants took part in the
RCT. At 24 months, weight loss was -2.1 kg (-4.3 to 0.0) for group (N = 51) and
1.1 kg (-2.7 to 0.4) for combination (N = 72). Outcomes for African American and
whites were similar. CONCLUSIONS: The intervention yielded substantial
improvement in diet, PA, and blood pressure, but weight loss was modest. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT01433484.
PMID- 27495297
TI - Acute arterial baroreflex-mediated changes in plasma catecholamine concentrations
in a chronic rat model of myocardial infarction.
AB - While it may be predictable that plasma norepinephrine (NE) concentration changes
with efferent sympathetic nerve activity (SNA) in response to baroreceptor
pressure inputs, an exact relationship between SNA and plasma NE concentration
remains to be quantified in heart failure. We examined acute baroreflex-mediated
changes in plasma NE and epinephrine (Epi) concentrations in normal control (NC)
rats and rats with myocardial infarction (MI) (n = 6 each). Plasma NE
concentration correlated linearly with SNA in the NC group (slope: 2.17 +/- 0.26
pg mL(-1) %(-1), intercept: 20.0 +/- 18.2 pg mL(-1)) and also in the MI group
(slope: 19.20 +/- 6.45 pg mL(-1) %(-1), intercept: -239.6 +/- 200.0 pg mL(-1)).
The slope was approximately nine times higher in the MI than in the NC group (P <
0.01). Plasma Epi concentration positively correlated with SNA in the NC group
(slope: 1.65 +/- 0.79 pg mL(-1) %(-1), intercept: 115.0 +/- 69.5 pg mL(-1)) and
also in the MI group (slope: 7.74 +/- 2.20 pg mL(-1) %(-1), intercept: 24.7 +/-
120.1 pg mL(-1)). The slope was approximately 4.5 times higher in the MI than in
the NC group (P < 0.05). Intravenous administration of desipramine (1 mg kg(-1))
significantly increased plasma NE concentration but decreased plasma Epi
concentration in both groups, suggesting that neuronal NE uptake had contributed
to the reduction in plasma NE concentration. These results indicate that high
levels of plasma catecholamine in MI rats were still under the influence of
baroreflex-mediated changes in SNA, and may provide additional rationale for
applying baroreflex activation therapy in patients with chronic heart failure.
PMID- 27495298
TI - Bidirectional variability in motor cortex excitability modulation following 1 mA
transcranial direct current stimulation in healthy participants.
AB - Due to the high interindividual response variability following transcranial
direct current stimulation (tDCS), it is apparent that further research of the
long-lasting effects of the stimulation technique is required. We aimed to
investigate interindividual variability following anodal tDCS and cathodal tDCS
in a large-scale prospective cross-over study. Motor cortex physiology
measurements were obtained using transcranial magnetic stimulation (TMS) in 59
healthy participants comparing motor-evoked potential (MEP) magnitudes following
two tDCS paradigms: 1 mA anodal tDCS for 13 min and 1 mA cathodal tDCS for 9 min.
Analysis compared MEP changes over time for both polarities. Additionally, we
applied hierarchical cluster analysis to assess the dynamics of poststimulation
changes. Overall, anodal tDCS resulted in a significant increase in corticospinal
excitability lasting for 40 min poststimulation, whereas cathodal tDCS did not
alter corticospinal excitability. Cluster analysis revealed for cathodal tDCS
both a cluster showing significant stable MEP reduction and a second cluster
displaying MEP increase over time. Two diametrical clusters were also found for
anodal tDCS Regardless of polarity, individuals with MEP increase following
stimulation showed steeper cortical recruitment curves compared to the clusters
with decreased MEP magnitudes. The observed findings confirm a bidirectional
modulation of corticospinal excitability following 1 mA tDCS in separate
subgroups and the relationship to cortical recruitment.
PMID- 27495300
TI - Retinal vein occlusion and the use of a dexamethasone intravitreal implant
(Ozurdex) in its treatment.
PMID- 27495299
TI - Treadmill exercise within lower body negative pressure protects leg lean tissue
mass and extensor strength and endurance during bed rest.
AB - Leg muscle mass and strength are decreased during reduced activity and non-weight
bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill
exercise within lower body negative pressure (LBNPEX) provides full-body weight
loading during BR and may prevent muscle deconditioning. We hypothesized that a
40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would
attenuate losses in leg lean mass (LLM), strength, and endurance during 6 degrees
head-down tilt BR, with similar benefits for men and women. Fifteen pairs of
healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with
one sibling of each twin pair assigned randomly as the non-exercise control (CON)
and the other twin as the exercise subject (EX). Before and after BR, LLM and
isokinetic leg strength and endurance were measured. Mean knee and ankle extensor
and flexor strength and endurance and LLM decreased from pre- to post-BR in the
male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle
extensor strength, and LLM were maintained in the male EX subjects. In contrast,
no pre- to post-BR changes were significant in the female subjects, either CON or
EX, likely due to their lower pre-BR values. Importantly, the LBNPEX
countermeasure prevents or attenuates declines in LLM as well as extensor leg
strength and endurance. Individuals who are stronger, have higher levels of
muscular endurance, and/or have greater LLM are likely to experience greater
losses during BR than those who are less fit.
PMID- 27495302
TI - Treatment for stage 4A retinopathy of prematurity: laser and/or ranibizumab.
AB - PURPOSE: Stage 4A retinopathy of prematurity (ROP) is a critical phase where
retinal detachment develops, but fovea is preserved. The present study aims to
evaluate the effect of the first treatment choice (laser photocoagulation (LPC)
or intravitreal ranibizumab (IVR)) applied in this critical phase on the
prognosis of the disease. METHODS: Records of patients diagnosed with stage 4A
ROP and whose first treatment was applied in our clinic were evaluated
retrospectively. All patients were referred to our clinic for the treatment of
advanced ROP . While group 1 was composed of the patients who were administered
LPC as first treatment, group 2 included patients where IVR was applied as first
treatment. The patients in both groups were referred to surgical treatment in the
presence of progression. RESULTS: The present study included a total of 31 eyes
in 16 patients with stage 4A ROP. Eighteen eyes of nine patients in group 1 were
first applied LPC, and 13 eyes of seven patients in group 2 were first applied
intravitreal ranibizumab. While anatomic outcomes of ten eyes in both groups were
favorable, eight eyes in group 1 and three eyes in group 2 displayed progression
and were referred to vitreoretinal surgery. CONCLUSIONS: Laser and/or IVR
treatment may be effective as a non-surgical treatment for stage 4A ROP.
Especially stage 4A ROP until 6 clock hours can regress without surgical
treatment. However, in stage 4A with involvement wider than 6 clock hours, non
surgical regression is difficult. Prospective controlled large series studies are
necessary.
PMID- 27495304
TI - A case of systemic lupus erythematosus presenting as bilateral avascular necrosis
of femur.
AB - BACKGROUND: Avascular necrosis occur as a result of diverse etiology. Chronic
inflammatory conditions such as systemic lupus erythematosus considered as a
recognize cause. Many cases were reported in systemic lupus erythematosus after
treating with corticosteroids. We report a case of a corticosteroid naive patient
presented as bilateral avascular necrosis of femoral head and later progressed to
a case of systemic lupus erythematosus. CASE PRESENTATION: A 26 year old lady
presented with right sided hip pain and diagnosed as avascular necrosis of the
femoral head. After 6 months she presented a similar pain in left hip, which
revealed avascular necrosis of left femoral head as well. A probable cause for
her clinical presentation could not be found after extensive clinical and
laboratory evaluation. Patient reported high erythrocyte sedimentation rate
persistently, and over the next few years progressed as a case of systemic lupus
erythematosus. CONCLUSION: Above case illustrated avascular necrosis could be an
early musculoskeletal manifestation of systemic lupus erythematosus even in the
absence of corticosteroid administration.
PMID- 27495305
TI - The Brexit broadcast that stoked fears over the NHS's future.
PMID- 27495303
TI - Difference in glaucoma progression between the first and second eye after
consecutive bilateral glaucoma surgery in patients with bilateral uveitic
glaucoma.
AB - PURPOSE: To determine whether the second eyes (SE) of patients with bilateral
uveitic glaucoma undergoing filtration surgery have more glaucomatous progression
in terms of visual acuity, visual field (VF) and optic nerve changes compared to
the first eyes (FE). METHODS: This retrospective study analysed data of 60 eyes
from 30 patients with bilateral uveitic glaucoma who had undergone glaucoma
surgery in both eyes on separate occasions. Humphrey VF progression was assessed
using the Progressor software. RESULTS: The pre-operative IOP between the FE
(43.1 +/- 7.7 mmHg) and SE (40 +/- 8.7 mmHg) was not statistically significant (p
= 0.15). IOP reduction was greater in the FE (64 %) than SE (59.7 %) post
operatively, but the mean IOP at the final visit in the FE (12.3 +/- 3.9 mmHg)
and SE (14.5 +/- 7 mmHg) was not statistically different (p = 0.2). There was no
significant change in mean logMAR readings pre and post-operatively (0.45 +/- 0.6
vs 0.37 +/- 0.6, p = 0.4) or between the FE and SE. The number of SE with CDR >
0.7 increased by 23 % compared to the FE. From 23 available VFs, five SE (21.7 %)
progressed at a median of five locations (range 1-11 points) with a mean local
slope reduction of 1.74 +/- 0.45 dB/year (range -2.39 to -1.26), whereas only one
FE progressed. However, there was no significant difference between mean global
rate of progression between the FE (-0.9 +/- 1.6 dB/year) and SE (-0.76 +/- 2.1
dB/year, p = 0.17) in the Humphrey VF. CONCLUSION: In eyes with bilateral uveitic
glaucoma requiring glaucoma surgery, the SEs had more progressed points on VF and
glaucomatous disc progression compared to FEs at the final visit.
PMID- 27495301
TI - Giant cell arteritis: ophthalmic manifestations of a systemic disease.
AB - BACKGROUND: Giant cell arteritis (GCA) is a systemic granulomatous vasculitis,
primarily affecting medium-large arteries. It has a predilection for the aorta
and its major branches, including the carotid and vertebral arteries. Ophthalmic
artery involvement frequently leads to irreversible visual loss, and therefore
GCA is one of the few true ophthalmic emergencies. GCA, although classified as a
large vessel vasculitis, is known to affect smaller-sized vessels, resulting in a
multiplicity of signs in the eye, some of which are often missed. PURPOSE: We set
out to highlight some of the less frequently observed clinical signs, which may
provide clues to clinically diagnosing GCA in patients presenting with non
classical features and inconclusive inflammatory markers. METHODS: We review the
literature and describe the diverse ocular features and some of the systemic
findings that can be associated with GCA. RESULTS: Although the most common
ocular manifestation of GCA is anterior ischaemic optic neuropathy, the clinical
presentation of GCA can vary dramatically. In the absence of obvious ocular
involvement, more subtle ophthalmic signs of anterior segment ischaemia, such as
hypotony and anisocoria, may be present at the time of initial clinical
examination. CONCLUSION: There are no specific biomarkers for disease to date;
therefore, pertinent history and clinical examination can guide towards diagnosis
in the acute setting. The diagnostic process is not always straightforward, yet
appropriate and prompt diagnosis is critical to enable timely intervention and
prevent significant morbidity.
PMID- 27495306
TI - Author's reply to Mathioudakis and colleagues.
PMID- 27495307
TI - Rainfall variation and child health: effect of rainfall on diarrhea among under 5
children in Rwanda, 2010.
AB - BACKGROUND: Diarrhea among children under 5 years of age has long been a major
public health concern. Previous studies have suggested an association between
rainfall and diarrhea. Here, we examined the association between Rwandan rainfall
patterns and childhood diarrhea and the impact of household sanitation variables
on this relationship. METHODS: We derived a series of rain-related variables in
Rwanda based on daily rainfall measurements and hydrological models built from
daily precipitation measurements collected between 2009 and 2011. Using these
data and the 2010 Rwanda Demographic and Health Survey database, we measured the
association between total monthly rainfall, monthly rainfall intensity, runoff
water and anomalous rainfall and the occurrence of diarrhea in children under 5
years of age. RESULTS: Among the 8601 children under 5 years of age included in
the survey, 13.2 % reported having diarrhea within the 2 weeks prior to the
survey. We found that higher levels of runoff were protective against diarrhea
compared to low levels among children who lived in households with unimproved
toilet facilities (OR = 0.54, 95 % CI: [0.34, 0.87] for moderate runoff and OR =
0.50, 95 % CI: [0.29, 0.86] for high runoff) but had no impact among children in
household with improved toilets. CONCLUSION: Our finding that children in
households with unimproved toilets were less likely to report diarrhea during
periods of high runoff highlights the vulnerabilities of those living without
adequate sanitation to the negative health impacts of environmental events.
PMID- 27495308
TI - SMARCE1 regulates metastatic potential of breast cancer cells through the
HIF1A/PTK2 pathway.
AB - BACKGROUND: While aberrant activation of the chromatin-remodeling SWI/SNF
complexes has been associated with cancer development and progression, the role
of each subunit in tumor cells is poorly defined. This study is aimed to
characterize the role of SMARCE1/BAF57 in regulating metastasis of breast cancer
cells. METHODS: Genetic approaches and chemical inhibitors were used to
manipulate the activities of SMARCE1 and its downstream targets in multiple
breast cancer cell lines. Xenograft mouse models were used to analyze the role of
SMARCE1 in lung metastasis in vivo. Nonadherent culture conditions were used to
elucidate the role of SMARCE1 in regulating anoikis. Chromatin
immunoprecipitation (ChIP), immunoprecipitation, and immunoblotting assays were
designed to dissect the mechanism of action of SMARCE1. Public databases were
used to investigate the relationship between SMARCE1 deregulation and breast
cancer prognosis. RESULTS: SMARCE1 knockdown reduced lung metastasis of breast
cancer cells and sensitized tumor cells to anoikis. In response to loss of
attachment, SMARCE1 interacted with and potentiated transcriptional activity of
HIF1A, resulting in rapid PTK2 activation. Both HIF1A and PTK2 were indispensable
for SMARCE1-mediated protection against anoikis by promoting activation of ERK
and AKT pathways while suppressing the expression of pro-apoptotic BIM protein.
Expression data analysis of a large cohort of human breast tumors revealed that
high expression of SMARCE1 or PTK2 is associated with poor prognosis and tumor
relapse, and PTK2 expression is positively correlated with SMARCE1 expression in
basal-like and luminal B subtypes of breast tumors. CONCLUSIONS: SMARCE1 plays an
essential role in breast cancer metastasis by protecting cells against anoikis
through the HIF1A/PTK2 pathway. SMARCE1-mediated PTK2 activation likely plays a
key role in promoting metastasis of basal-like and luminal B subtype of breast
tumors.
PMID- 27495309
TI - No inequalities in survival from colorectal cancer by education and socioeconomic
deprivation - a population-based study in the North Region of Portugal, 2000
2002.
AB - BACKGROUND: Association between cancer survival and socioeconomic status has been
reported in various countries but it has never been studied in Portugal. We aimed
here to study the role of education and socioeconomic deprivation level on
survival from colorectal cancer in the North Region of Portugal using a
population-based cancer registry dataset. METHODS: We analysed a cohort of
patients aged 15-84 years, diagnosed with a colorectal cancer in the North Region
of Portugal between 2000 and 2002. Education and socioeconomic deprivation level
was assigned to each patient based on their area of residence. We measured
socioeconomic deprivation using the recently developed European Deprivation
Index. Net survival was estimated using Pohar-Perme estimator and age-adjusted
excess hazard ratios were estimated using parametric flexible models. Since no
deprivation-specific life tables were available, we performed a sensitivity
analysis to test the robustness of the results to life tables adjusted for
education and socioeconomic deprivation level. RESULTS: A total of 4,105 cases
were included in the analysis. In male patients (56.3 %), a pattern of worse 5-
and 10-year net survival in the less educated (survival gap between extreme
education groups: -7 % and -10 % at 5 and 10 years, respectively) and more
deprived groups (survival gap between extreme EDI groups: -5 % both at 5 and 10
years) was observed when using general life tables. No such clear pattern was
found among female patients. In both sexes, when likely differences in background
mortality by education or deprivation were accounted for in the sensitivity
analysis, any differences in net survival between education or deprivation groups
vanished. CONCLUSIONS: Our study shows that observed differences in survival by
education and EDI level are most likely attributable to inequalities in
background survival. Also, it confirms the importance of using the relevant life
tables and of performing sensitivity analysis when evaluating socioeconomic
inequalities in cancer survival. Comparison studies of different healthcare
systems organization should be performed to better understand its influence on
cancer survival inequalities.
PMID- 27495310
TI - Characterization of BRCA1 and BRCA2 variants found in a Norwegian breast or
ovarian cancer cohort.
AB - Germline mutations in BRCA1 and BRCA2 cause hereditary breast and ovarian cancer.
Molecular screening of these two genes in patients with a family history of
breast or ovarian cancer has revealed pathogenic variants as well as genetic
variants of unknown significance (VUS). These VUS may cause a challenge in the
genetic counseling process regarding clinical management of the patient and the
family. We investigated 32 variants previously detected in 33 samples from
patients with a family history of breast or ovarian cancer. cDNA was analyzed for
alternative transcripts and selected missense variants located in the BRCT
domains of BRCA1 were assessed for their trans-activation ability. Although an
extensive cDNA analysis was done, only three of the 32 variants appeared to
affect the splice-process (BRCA1 c.213-5T>A, BRCA1 c.5434C>G and BRCA2 c.68
7T>A). In addition, two variants located in the BRCT domains of BRCA1 (c.5075A>C
p.Asp1692Ala and c.5513T>G p.Val1838Gly) were shown to abolish the BRCT domain
trans-activation ability, whereas BRCA1 c.5125G>A p.Gly1709Arg exhibited equal
trans-activation capability as the WT domain. These functional studies may offer
further insights into the pathogenicity of certain identified variants; however,
this assay is only applicable for a subset of missense variants.
PMID- 27495312
TI - God in the brain: Experiencing psychosis in the postsecular United States.
AB - There is a growing literature on what contemporary cultural theorists have
broadly termed the "postsecular": the abandonment of clear-cut boundaries between
the secular and nonsecular in the industrialized West and an embrace of a complex
understanding of what is real that neither accepts nor rejects the supernatural.
These new cultural currents may affect not only philosophers and theologians, but
also the ways in which individuals with psychosis make sense of their
experiences. This paper reports on the key findings of an in-depth qualitative
analysis of 19 interviews of individuals diagnosed with psychotic disorders. The
majority of participants described ongoing and self-conscious struggles to
demarcate their experiences as the products of the real world or a "crazy" mind.
With equal frequency, participants weighed and debated competing secular and
supernatural explanations, often juxtaposing and blending different explanatory
frameworks. We found that this syncretic process affected not only the content of
psychotic experiences-what delusions or hallucinations are about-but also the
type of arguments or logics used to justify particular interpretations. We
discuss the implications of these observations with respect to clinical practice
and the broader phenomenology of psychosis, challenging often oversimplified
discourse on "insight" and suggesting that polarization(s) between "biomedical"
and "psychosocial" explanations may be of less relevance to patients' real-world
experiences than is often assumed.
PMID- 27495311
TI - Comparative genomics and transcriptomics of Pichia pastoris.
AB - BACKGROUND: Pichia pastoris has emerged as an important alternative host for
producing recombinant biopharmaceuticals, owing to its high cultivation density,
low host cell protein burden, and the development of strains with humanized
glycosylation. Despite its demonstrated utility, relatively little strain
engineering has been performed to improve Pichia, due in part to the limited
number and inconsistent frameworks of reported genomes and transcriptomes.
Furthermore, the co-mingling of genomic, transcriptomic and fermentation data
collected about Komagataella pastoris and Komagataella phaffii, the two strains
co-branded as Pichia, has generated confusion about host performance for these
genetically distinct species. Generation of comparative high-quality genomes and
transcriptomes will enable meaningful comparisons between the organisms, and
potentially inform distinct biotechnological utilies for each species. RESULTS:
Here, we present a comprehensive and standardized comparative analysis of the
genomic features of the three most commonly used strains comprising the tradename
Pichia: K. pastoris wild-type, K. phaffii wild-type, and K. phaffii GS115. We
used a combination of long-read (PacBio) and short-read (Illumina) sequencing
technologies to achieve over 1000X coverage of each genome. Construction of
individual genomes was then performed using as few as seven individual contigs to
create gap-free assemblies. We found substantial syntenic rearrangements between
the species and characterized a linear plasmid present in K. phaffii. Comparative
analyses between K. phaffii genomes enabled the characterization of the
mutational landscape of the GS115 strain. We identified and examined 35 non
synonomous coding mutations present in GS115, many of which are likely to impact
strain performance. Additionally, we investigated transcriptomic profiles of gene
expression for both species during cultivation on various carbon sources. We
observed that the most highly transcribed genes in both organisms were
consistently highly expressed in all three carbon sources examined. We also
observed selective expression of certain genes in each carbon source, including
many sequences not previously reported as promoters for expression of
heterologous proteins in yeasts. CONCLUSIONS: Our studies establish a foundation
for understanding critical relationships between genome structure, cultivation
conditions and gene expression. The resources we report here will inform and
facilitate rational, organism-wide strain engineering for improved utility as a
host for protein production.
PMID- 27495313
TI - Aroma volatile analyses and 2AP characterization at various developmental stages
in Basmati and Non-Basmati scented rice (Oryza sativa L.) cultivars.
AB - BACKGROUND: Rice plant growth is comprised of distinct phases, such as
vegetative, reproductive, grain filling and maturity phases. In these phases
synthesis and availability of primary and secondary metabolites including
volatile organic compounds (VOC's) is highly variable. In scented rice, aroma
volatiles are synthesized in aerial plant parts and deposited in mature grains.
There are more than 100 VOCs reported to be responsible for flavor in basmati
rice. It will be interesting to keep track of aroma volatiles across the
developmental stages in scented rice. Therefore, the aroma volatiles contributing
in aroma with special reference to the major compound 2 acetyl-1-pyrroline (2AP)
were screened at seven developmental stages in scented rice cultivars Basmati-370
and Ambemohar-157 along with non-scented rice cultivar IR-64 as a control
following HS-SPME-GC-MS method. In addition, the expression levels of key genes
and precursor levels involved in 2AP biosynthesis were studied. RESULTS: The
study indicated that volatilome of scented rice cultivars is more complex than
non-scented rice cultivar. N-heterocyclic class was the major distinguishing
class between scented from non-scented rice. A total of 14 compounds including,
2AP were detected specifically in scented rice cultivars. Maximum number of
compounds were synthesized at seedling stage and decreased gradually at
reproductive and maturity. The seedling stage is an active phase of development
where maximum number green leaf volatiles were synthesized which are known to act
as defense molecules for protection of young plant parts. Among the 14 odor
active compounds (OACs), 10 OACs were accumulated at higher concentrations
significantly in scented rice cultivars and contribute in the aroma. 2AP content
was highest in mature grains followed by at booting stage. Gene expression
analysis revealed that reduced expression of betaine aldehyde dehydrogenase 2
(badh2) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and elevated level
of triose phosphate isomerase (TPI) and Delta1-Pyrolline-5-carboxylic acid
synthetase (P5CS) transcript enhances 2AP accumulation. CONCLUSIONS: Most diverse
compounds were synthesized at seedling stage and OACs were accumulated more at
flowering followed by seedling stage. Distinct accumulation pattern exists for
2AP and other aroma volatiles at various developmental stages. The study revealed
the mechanism of 2AP accumulation such that 2AP in mature grains might be
transported from leaves and stem sheath and accumulation takes place in grains.
PMID- 27495314
TI - [Phoneme discrimination training with experienced cochlear implant listeners].
AB - BACKGROUND: Computer-based auditory training programmes seem to be a useful tool
in the process of auditory rehabilitation after cochlear implantation (CI).
Currently, little is known about the learning mechanism and efficiency of such
programs. The aim of the study was to evaluate a specific auditory training
programme for phoneme discrimination in experienced CI listeners. MATERIALS AND
METHODS: A total of 15 CI adult listeners with more than 2 years' CI experience
participated in the auditory training. Over a period of 3 weeks they were
instructed to train their phoneme discrimination via computer twice a week.
Training material consisted of special syllables for consonants (vCv) and vowels
(cVc) discrimination. RESULTS: The discrimination abilities for consonants and
vowels improved significantly over the training period for training group
participants, whereas the changes for the consonants were higher. In addition,
the improvement for voiced and unvoiced consonants was significant. CONCLUSION:
Computerised auditory training with phonemes improves CI listeners'
discrimination abilities for consonants and vowels.
PMID- 27495315
TI - The Effect of Unenhanced MRI on the Surgeons' Decision-Making Process in Females
with Suspected Appendicitis.
AB - BACKGROUND: This prospective study evaluated the impact of the results of
unenhanced magnetic resonance imaging (MRI) on the surgeon's diagnosis of acute
appendicitis in potentially fertile females. METHODS: 112 female patients, aged
12-55, with suspected appendicitis underwent MRI of the abdomen. At three defined
intervals; admission and clinical re-evaluation before and after revealing the
MRI results, the surgeon recorded the attendance of each patient in operative
treatment, observation or discharge. Appendicitis was confirmed or declined by
pathology or by telephone follow-up in case of non-intervention. FINDINGS:
Appendicitis was confirmed in 29 of 112 patients. At admission the surgeon's
disposition had a sensitivity of 97 % and specificity of 29 %. After knowing the
MRI results, sensitivity was 97 % and specificity 64 %. The sensitivity and
specificity of MRI alone were 89 and 100 %, with a negative and positive
predictive value of 96 and 100 %, respectively. CONCLUSION: We believe that MRI
should perhaps be standard in all female patients during their reproductive years
with suspected appendicitis. It avoids an operation in 32 % of cases and allows
earlier planning for patients with an equivocal clinical picture. Trial number:
OND1292733 (Narcis.nl).
PMID- 27495317
TI - Mentored Writing: An Arts-Based Curriculum for First-Year Psychiatry Residents.
PMID- 27495316
TI - Yttrium-90 Radioembolization for Hepatocellular Carcinoma Prior to Liver
Transplantation.
AB - BACKGROUND: Liver transplantation (LT) is a well-established procedure for
hepatocellular carcinoma (HCC) within the Milan criteria. Yttrium-90 microspheres
radioembolization (Y90-RE) has shown to be an effective and safe treatment of
primary liver tumors. We retrospectively evaluate the efficacy of the Y90-RE in
patients with HCC prior to LT. METHODS: From January 2002 to December 2015, 365
patients were transplanted at the San Camillo Hospital Center. One hundred forty
three patients were transplanted for HCC, and in 22 cases the patients were
treated with Y90-RE before LT. RESULTS: Three patients were treated with Y90-RE
within the Milan criteria, and 19 patients were out of criteria before Y90-RE.
Four patients had an increasing MELD score between Y90-RE and LT. On the other
hand, alpha-fetoprotein decreases after Y90-RE treatment in all cases. No patient
death was observed in Y90-RE procedure or at LT. In 78.9 % of cases, a successful
downstaging was observed, and in 100 % of cases bridging was achieved. From Y90
RE treatment overall survival was 43.9 months. From LT, overall mean survival was
30.2 months with a free survival of 29.6 months. The overall survival after LT
analysis between the patients treated with Y90-RE and patients without was not
significant (p = 0.113). Free survival analysis was not significant (p = 0.897)
between the two populations. CONCLUSIONS: We successfully performed LT in
patients after Y90-RE treatment both as bridging and downstaging for HCC and
obtained a similar overall and free survival of LT for HCC within Milan criteria.
Y90-RE becomes a real option to provide curative therapy for patients who
traditionally are not considered eligible for surgery.
PMID- 27495318
TI - The small RNA SraG participates in PNPase homeostasis.
AB - The rpsO-pnp operon encodes ribosomal protein S15 and polynucleotide
phosphorylase, a major 3'-5' exoribonuclease involved in mRNA decay in
Escherichia coli The gene for the SraG small RNA is located between the coding
regions of the rpsO and pnp genes, and it is transcribed in the opposite
direction relative to the two genes. No function has been assigned to SraG.
Multiple levels of post-transcriptional regulation have been demonstrated for the
rpsO-pnp operon. Here we show that SraG is a new factor affecting pnp expression.
SraG overexpression results in a reduction of pnp expression and a
destabilization of pnp mRNA; in contrast, inhibition of SraG transcription
results in a higher level of the pnp transcript. Furthermore, in vitro
experiments indicate that SraG inhibits translation initiation of pnp Together,
these observations demonstrate that SraG participates in the post-transcriptional
control of pnp by a direct antisense interaction between SraG and PNPase RNAs.
Our data reveal a new level of regulation in the expression of this major
exoribonuclease.
PMID- 27495319
TI - Gld2-catalyzed 3' monoadenylation of miRNAs in the hippocampus has no detectable
effect on their stability or on animal behavior.
AB - Gld2, a noncanonical cytoplasmic poly(A) polymerase, interacts with the RNA
binding protein CPEB1 to mediate polyadenylation-induced translation in dendrites
of cultured hippocampal neurons. Depletion of Gld2 from the hippocampus leads to
a deficit in long-term potentiation evoked by theta burst stimulation. At least
in mouse liver and human primary fibroblasts, Gld2 also 3' monoadenylates and
thereby stabilizes specific miRNAs, which enhance mRNA translational silencing
and eventual destruction. These results suggest that Gld2 would be likely to
monoadenylate and stabilize miRNAs in the hippocampus, which would produce
measurable changes in animal behavior. We now report that using Gld2 knockout
mice, there are detectable alterations in specific miRNA monoadenylation in the
hippocampus when compared to wild type, but that these modifications produce no
detectable effect on miRNA stability. Moreover, we surprisingly find no overt
change in animal behavior when comparing Gld2 knockout to wild-type mice. These
data indicate that miRNA monoadenylation-mediated stability is cell type-specific
and that monoadenylation has no measurable effect on higher cognitive function.
PMID- 27495320
TI - Chitosan silver nanocomposite (CAgNC) as an antifungal agent against Candida
albicans.
AB - Due to limited numbers of antifungal drugs and emergence of drug resistance have
directed to develop nonconventional therapeutic agents against fungal pathogen
Candida albicans. In this study, anticandidal activity of chitosan silver
nanocomposite (CAgNC) was tested against C. albicans Minimum inhibitory
concentration (MIC) and minimum fungicidal concentration (MFC) of CAgNC were
determined as 25 and 100 MUg/ml, respectively. Electron microscopic image results
confirmed the ultrastructural cell wall deformities and injuries caused by CAgNC.
Propidium iodide (PI) penetration into the CAgNC treated cells could be
considered as an evidence for loss of cell membrane integrity and cell death at
MFC. Level of intracellular reactive oxygen species (ROS) was increased, while
cell viability was decreased with the increased of CAgNC concentrations. In our
protein profile results, several induced proteins were observed under CAgNC
treatment, and they could be related to multidrug and stress resistant proteins
such as CDR1 (55 kDa) and CaHSP70 based on the protein band size. CAgNC mediated
cell wall damage, loss of cell membrane integrity, elevated ROS level, and
associated oxidative stress have been identified as the main causative factors
for the anticandidal activity. Overall results from our study indicated that
CAgNC could affect negatively on physiological and biochemical functions of C.
albicans suggesting CAgNC as a potential alternative for antifungal chemotherapy.
PMID- 27495321
TI - Fungemia due to rare opportunistic yeasts: data from a population-based
surveillance in Spain.
AB - Fungemia due to rare yeasts constitutes an emerging but poorly investigated
condition. Data on risk factors, clinical features, therapy, and outcome of
episodes of fungemia due to rare (non-Candida, non-Cryptococcus) yeasts were
analyzed in a population-based surveillance program conducted in 29 Spanish
hospitals between May 2010 and April 2011. Species identification (DNA
sequencing) and antifungal susceptibility testing (EUCAST and CLSI methods) were
centrally performed. Fourteen out of 767 episodes of fungemia (1.8%) were due to
rare yeasts: Trichosporon asahii, Magnusiomyces capitatus (three cases each),
Rhodotorula mucilaginosa, Wickerhamomyces anomalus (two cases each), and Pichia
kudriavzevii, Cyberlindnera fabianii, Kodamaea ohmeri, and Lodderomyces
elongisporus (one case each). Misidentification by local laboratories was
observed in two isolates. Breakthrough fungemia occurred in two episodes due to
M. capitatus MIC values for echinocandins were generally high (particularly for
M. capitatus, T. asahii, and R. mucilaginosa isolates [>=2 mg/l]), whereas T.
asahii isolates showed MICs >=1 mg/l to amphotericin B. Patients with fungemia
due to rare yeasts were more likely to have hematological malignancies (28.6% vs.
7.8%; P-value = .021), chronic lung disease (50.0% vs. 22.3%; P-value = .023),
and prior immunosuppression (57.1% vs. 22.2%; P-value = .005) compared to those
with candidemia. The rate of clinical failure (persistent fungemia and/or 30-day
mortality) was 46.2% and did not significantly differ from that observed in
episodes of candidemia. In conclusion, non-Candida, non-Cryptococcus yeasts are
uncommon causes of fungemia, with immunosuppression and chronic lung disease as
predisposing factors. Outcome does not appear to be worse than that of
candidemia.
PMID- 27495322
TI - Risk factors for drainage-requiring ascites after refractory peritonitis in
peritoneal dialysis patients.
AB - PURPOSE: Refractory peritonitis remains a thorny issue for patients with chronic
peritoneal dialysis (PD). Shortly after catheter removal, some patients develop
persistent peritoneal inflammation and ascites formation, which require
percutaneous drainage for symptom relief. Our study aimed at finding the risk
factors for this kind of event. METHODS: A total of 47 PD patients complicated
with refractory peritonitis who underwent catheter removal between January 2009
and December 2011 were enrolled in this study. Data were compared between
patients with and without the development of symptomatic ascites requiring
drainage during hospitalization. RESULTS: Among the 47 refractory peritonitis
patients, 15 patients developed symptomatic ascites that needed further drainage
shortly after catheter removal during hospitalization. The following factors were
associated with an increased risk: longer dialysis duration, higher peritoneal
Kt/V urea, and a significant rise in serum C-reactive protein (CRP) level after
catheter removal. These patients had a prolonged hospital stay (62 vs 21 days, P
< 0.001) and a significantly higher risk of recurrent loculated ascites during
subsequent 6 months of follow-up (33.3 vs 6.2 %, P = 0.022) compared with
patients who did not develop ascites requiring drainage during hospitalization.
CONCLUSION: A significant portion of patients with refractory PD peritonitis
experienced ascites requiring drainage shortly after catheter removal, which led
to a prolonged hospitalization. Whether routine drain placement at the time of
catheter removal for this high-risk group would be of benefit warrants further
prospective studies.
PMID- 27495323
TI - Does a history of bullying and abuse predict lower urinary tract symptoms,
chronic pain, and sexual dysfunction?
AB - PURPOSE: To investigate associations of bullying and abuse with pelvic floor
symptoms, urogenital pain, and sexual health characteristics of women presenting
to a multidisciplinary women's urology center. METHODS: Retrospective review of a
prospective database. Patients completed questions about bullying, abuse, sexual
health and validated questionnaires including the Pelvic Floor Dysfunction
Inventory (PFDI-20), Overactive Bladder Questionnaire (OAB-q), and visual analog
scale (VAS 0-10) for genitourinary pain. Statistical analyses included Chi
squared and t tests, which compared victims of bullying and/or abuse to non
victims. RESULTS: Three hundred and eighty patients were reviewed. Three hundred
and thirty-eight had data on bullying and abuse history. Out of 380, 94 (24.7 %)
reported that they were victims of bullying. Out of 380, 104 (27.4 %) reported
that they were victims of abuse. Women with a history of bullying and abuse had
increased overall pain scores compared to those without a history of either.
Women with a history of abuse and bullying had increased PFDI-20, POPDI, and UDI
6 scores compared to women who were not bullied or abused. There was no
difference in being sexually active or in sexual satisfaction between the groups.
Patients with a history of abuse and bullying had the greatest percentage of
dyspareunia (p = 0.009). CONCLUSIONS: Women with a history of bullying, abuse, or
both predict increased pelvic floor distress, urological symptoms, increased
urogenital pain, and increased dyspareunia. Clinicians should screen for exposure
to bullying or abuse in order to provide comprehensive resources to address these
psychosocial issues.
PMID- 27495324
TI - Povidone-iodine rectal cleansing and targeted antimicrobial prophylaxis using
rectal swab cultures in men undergoing transrectal ultrasound-guided prostate
biopsy are associated with reduced incidence of postoperative infectious
complications.
AB - PURPOSE: The aim of this study was to evaluate the effect of povidone-iodine
rectal disinfection and targeted antimicrobial prophylaxis in men undergoing
transrectal ultrasound-guided prostate biopsy based on rectal swab culture
results. METHODS: From January 2011 to December 2015, we studied differences in
infectious complications in men who received povidone-iodine rectal disinfection
with targeted antimicrobial prophylaxis and those who received empirical
prophylaxis before transrectal ultrasound-guided prostate biopsy. Clinical
variables including demographics, prior antibiotic, rectal swab culture results,
povidone-iodine rectal cleansing, antibiotic prophylaxis, and infectious
complications were evaluated. Patients were divided into three groups as follows:
Group A received no povidone-iodine rectal cleansing but received empirical
antimicrobial prophylaxis; group B received povidone-iodine rectal cleansing and
empirical antimicrobial prophylaxis; and group C received povidone-iodine rectal
cleansing and targeted antimicrobial prophylaxis. RESULTS: Patients were divided
into group A (n = 192; 13.2 %), group B (n = 579; 39.9 %), or group C (n = 679;
46.8 %). In groups A and B, all patients received fluoroquinolone antimicrobial
prophylaxis. Group C patients received targeted antimicrobial prophylaxis
according to antibiotic resistance of rectal flora, and 71.1 % of these received
fluoroquinolone antimicrobial prophylaxis. Infectious complication rates were
3.6, 2.9, and 1.3 % in group A, group B, and group C, respectively. Incidences of
acute prostatitis and bacteremia were significantly lower in group C (p = 0.041
and p = 0.049, respectively) than in the other groups. CONCLUSIONS: In the era of
quinolone resistance, the combination of povidone-iodine rectal cleansing and
targeted antibiotic prophylaxis may reduce the rate of infectious complications.
PMID- 27495326
TI - Detection of object onsets and offsets: Does the primacy of onset persist even
with bias for detecting offset?
AB - Onset primacy is a robust visual phenomenon in which appearance of new objects
(onsets) in a scene more effectively captures observers' attention compared with
disappearance of previously viewed objects (offsets). We hypothesized that the
human attentional system is programmed by default to prioritize the processing of
onsets, because quick detection of them is advantageous in most situations.
However, the attentional priority may be able to flexibly adapt to the detection
of object offsets depending on observers' behavioral goals. To test these
hypotheses, two experiments were conducted in which participants were biased
toward finding offset of an existing object through top-down and bottom-up
manipulations. Results showed that although onset primacy was reduced to some
degree under strong offset bias, in general participants continued to detect
onsets efficiently. These findings did not eliminate the possibility of
attentional flexibility, but they do demonstrate the robustness of onset primacy,
suggesting that environmental demands or motivational factors would need to be
sufficiently strong for people to switch to an adaptive attentional mode.
PMID- 27495325
TI - Factors influencing general practitioners' decisions about cardiovascular disease
risk reassessment: findings from experimental and interview studies.
AB - BACKGROUND: Guidelines on cardiovascular disease (CVD) risk reassessment
intervals are unclear, potentially leading to detrimental practice variation: too
frequent can result in overtreatment and greater strain on the healthcare system;
too infrequent could result in the neglect of high risk patients who require
medication. This study aimed to understand the different factors that general
practitioners (GPs) consider when deciding on the reassessment interval for
patients previously assessed for primary CVD risk. METHODS: This paper combines
quantitative and qualitative data regarding reassessment intervals from two
separate studies of CVD risk management. Experimental study: 144 Australian GPs
viewed a random selection of hypothetical cases via a paper-based questionnaire,
in which blood pressure, cholesterol and 5-year absolute risk (AR) were
systematically varied to appear lower or higher. GPs were asked how they would
manage each case, including an open-ended response for when they would reassess
the patient. Interview study: Semi-structured interviews were conducted with a
purposive sample of 25 Australian GPs, recruited separately from the GPs in the
experimental study. Transcribed audio-recordings were thematically coded, using
the Framework Analysis method. RESULTS: EXPERIMENT: GPs stated that they would
reassess the majority of patients across all absolute risk categories in 6 months
or less (low AR = 52 % [CI95% = 47-57 %], moderate AR = 82 % [CI95% = 76-86 %],
high AR = 87 % [CI95% = 82-90 %], total = 71 % [CI95% = 67-75 %]), with 48 %
(CI95% = 43-53 %) of patients reassessed in under 3 months. The majority (75 %
[CI95% = 70-79 %]) of patients with low-moderate AR (<=15 %) and an elevated risk
factor would be reassessed in under 6 months. Interviews: GPs identified
different functions for reassessment and risk factor monitoring, which affected
recommended intervals. These included perceived psychosocial benefits to
patients, preparing the patient for medication, and identifying barriers to
lifestyle change and medication adherence. Reassessment and monitoring intervals
were driven by patient motivation to change lifestyle, patient demand, individual
risk factors, and GP attitudes. CONCLUSIONS: There is substantial variation in
reassessment intervals for patients with the same risk profile. This suggests
that GPs are not following reassessment recommendations in the Australian
guidelines. The use of shorter intervals for low-moderate AR contradicts research
on optimal monitoring intervals, and may result in unnecessary costs and over
treatment.
PMID- 27495327
TI - Concern for Lost Income Following Donation Deters Some Patients From Talking to
Potential Living Donors.
AB - CONTEXT: Some living kidney donors report lost income during recovery from
surgery. Little is known about whether concern for living donor's lost income
affects the decision to undergo donation evaluation and the willingness of
transplant candidates to discuss living kidney donation (LKD) with others.
OBJECTIVE: To examine whether transplant patients were told by potential donors
about lost income concerns and whether patients chose not to discuss LKD with
others due to lost income concerns. DESIGN, SETTING, AND PATIENTS: Kidney
transplant patients (185 wait-listed candidates, 171 deceased donor recipients,
and 100 live donor recipients) at 2 centers completed a questionnaire to assess
whether concern about donor's lost income was a consideration in discussion about
LKD with others. RESULTS: One-third (32%) were told by a family member/friend
that they were willing to donate but were concerned about potential lost income.
The majority of those who expressed financial concern (64%) did not initiate
donation evaluation. Many patients (42%) chose not to discuss living donation
with a family member/friend due to concern about the impact of lost income on the
donor. In the multivariable model, lower annual household income was the only
statistically significant predictor of both having a potential donor expressing
lost income concern and choosing not to talk to someone because of lost income
concern. CONCLUSION: Findings from the current study underscore how concern about
income loss for living donors may affect decision-making by both transplant
candidates and potential donors.
PMID- 27495328
TI - MovingU: A prospective cohort study to understand behavioural and environmental
contexts influencing physical activity during the transition into emerging
adulthood.
AB - BACKGROUND: Children and youth are often considered the most active segment of
the population, however, research indicates that physical activity (PA) tends to
peak during the adolescent years, declining thereafter with age. In particular,
the acute transition out of high school is a period for which individuals appear
to be at high-risk for becoming less active. Relatively few studies have
investigated the factors influencing the changes in PA during this transition
period. Therefore the purpose of the MovingU study is to gain a comprehensive
understanding of the behavioural patterns and the socio-ecological factors
related to the changes in PA during the transition out of high school.
METHODS/DESIGN: MovingU is comprised of two phases. Phase I is a prospective
cohort design and aims to follow 120 students in their last year of high school
through to their first year out of high school. Students will be asked to
complete questionnaires measuring various psychosocial and socio-environmental
variables (e.g., self-efficacy and distress) four times throughout this
transition period. Students will also be given a wrist-worn accelerometer to wear
for 7-days at each of the four assessments. Phase II is a cross-sectional study
involving 100 first-year university students. Students will be asked to complete
the same questionnaire from phase I, wear a wrist-worn accelerometer for 5-days,
and complete ecological momentary assessments (EMA) using their smartphones at
randomly selected times throughout the day for 5-days. EMA items will capture
information regarding contextual and momentary correlates of PA. DISCUSSION: The
MovingU study represents the first to evaluate the social and environmental
influences of PA behaviour changes, including the use of intensive real-time data
capture strategies during the transition out of high school. This information
will be critical in the development of interventions aimed to prevent or
attenuate such drastic declines in PA during emerging adulthood period.
PMID- 27495329
TI - Direct transfer of HRPII-magnetic bead complexes to malaria rapid diagnostic
tests significantly improves test sensitivity.
AB - BACKGROUND: The characteristic ease of use, rapid time to result, and low cost of
malaria rapid diagnostic tests (RDTs) promote their widespread use at the point
of-care for malaria detection and surveillance. However, in many settings, the
success of malaria elimination campaigns depends on point-of-care diagnostics
with greater sensitivity than currently available RDTs. To address this need, a
sample preparation method was developed to deliver more biomarkers onto a malaria
RDT by concentrating the biomarker from blood sample volumes that are too large
to be directly applied to a lateral flow strip. METHODS: In this design, Ni-NTA
functionalized magnetic beads captured the Plasmodium falciparum biomarker HRPII
from a P. falciparum D6 culture spiked blood sample. This transfer of magnetic
beads to the RDT was facilitated by an inexpensive 3D-printed apparatus that
aligned the sample tube with the sample deposition pad and a magnet beneath the
RDT. Biomarkers were released from the bead surface onto the lateral flow strip
using imidazole-spiked running buffer. Kinetics of HRPII binding to the Ni-NTA
beads as a function of blood sample volume were explored prior to determining the
effect of the proposed method on the limit of detection of Paracheck RDTs.
RESULTS: More than 80 % of HRPII biomarkers were extracted from blood sample
volumes ranging from 25 to 250 uL. The time required to reach 80 % binding ranged
from 5 to 60 min, depending on sample volume. Using 250 MUL of blood and a 30-min
biomarker binding time, the limit of detection of the Paracheck Pf RDT brand was
improved by 21-fold, resulting in a limit of detection below 1 parasite/MUL.
CONCLUSIONS: This approach has the sensitivity and simplicity required to assist
in malaria elimination campaigns in settings with limited access to clinical and
laboratory resources.
PMID- 27495330
TI - Intraoperative workload in robotic surgery assessed by wearable motion tracking
sensors and questionnaires.
AB - BACKGROUND: The introduction of robotic technology has revolutionized radical
prostatectomy surgery. However, the potential benefits of robotic techniques may
have trade-offs in increased mental demand for the surgeon and the physical
demand for the assisting surgeon. This study employed an innovative motion
tracking tool along with validated workload questionnaire to assess the
ergonomics and workload for both assisting and console surgeons intraoperatively.
METHODS: Fifteen RARP cases were collected in this study. Cases were performed by
10 different participants, six primarily performed console tasks and four
primarily performed assisting tasks. Participants had a median 12 (min-3, max-25)
years of surgical experience. Both console and assisting surgeons performed
robotic prostatectomy cases while wearing inertial measurement units (IMUs) that
continuously track neck, shoulder, and torso motion without interfering with the
sterile environment. Postoperatively, participants completed a workload
questionnaire (SURG-TLX) and a body part discomfort questionnaire. RESULTS:
Twenty-six questionnaires were completed from 13 assisting and 13 console
surgeons over the 15 cases. Postoperative pain was reported highest for the right
shoulder and neck. Mental demands were 41 % higher for surgeons at the console
than assisting (p < 0.05), while physical demands were not significantly
different. Assisting surgeons worked in demanding neck postures for 58 % of the
procedure compared to 24 % for the console surgeon (p < 0.01). Surgeons at the
console were primarily static and showed 2-5 times fewer movements than assisting
surgeons (p < 0.01). CONCLUSIONS: Postures were more ergonomic during console
tasks than when assisting by the bedside; however, the console may constrain
postures leading to static loads that have been associated with musculoskeletal
symptoms for the neck, torso, and shoulders. The IMU sensors were effective at
quantifying ergonomics in robotic prostatectomies, and these methods and findings
have broad applications to other robotic procedures.
PMID- 27495331
TI - Esophageal stent fixation with endoscopic suturing device improves clinical
outcomes and reduces complications in patients with locally advanced esophageal
cancer prior to neoadjuvant therapy: a large multicenter experience.
AB - BACKGROUND: Endoscopic placement of fully covered self-expanding metal stents
(FCSEMS) to treat malignant dysphagia in patients with esophageal cancer
significantly improves dysphagia; however, these stents have a high migration
rate. AIM: To determine whether FCSEMS fixation using an endoscopic suturing
device treated malignant dysphagia and prevented stent migration in patients with
locally advanced esophageal cancer receiving neoadjuvant therapy when compared to
patients with FCSEMS placement alone. METHOD: A review of patients with locally
advanced esophageal cancer who underwent FCSEMS placement at 3 centers was
performed. Patients were divided into two groups: Group A (n = 26) was composed
of patients who underwent FCSEMS placement with suture placement, and Group B (n
= 67) was composed of patients with FCSEMS placement alone. RESULTS: There were
no significant differences between Groups A and B in demographics, and tumor
characteristics. The technical success rate for stent placement was 100 %. There
was no difference between Groups A and B in the median stent diameter and stent
lengths. Mean dysphagia score obtained at 1 week after stent placement had
improved significantly from baseline (2.4 and 1, respectively, p < 0.001).
Patients had a median follow-up of 4 months. Immediate adverse events were mild
chest discomfort in 4 patients in Group A and 2 patients in Group B (p = 0.05),
and significant acid reflux in 3 patient in Group A compared to 2 patients in
Group B (p = 0.1). The stent migration rate was significantly lower in Group A
compared to compared to Group B (7.7 vs 26.9 %, respectively, p = 0.004). There
was a delayed perforation in 1 patient and 1 death due to aspiration pneumonia in
Group B. CONCLUSION: Fixation of esophageal FCSEMSs by using an endoscopic
suturing device in patients receiving neoadjuvant therapy was shown to be
feasible, safe, and relatively effective at preventing stent migration compared
to those who had stent placed alone.
PMID- 27495333
TI - Learning curves and surgical outcomes for proctored adoption of laparoscopic
ventral mesh rectopexy: cumulative sum curve analysis.
AB - BACKGROUND: Laparoscopic ventral mesh rectopexy (VMR) is an effective and well
recognised treatment for symptoms of obstructive defecation in the context of
rectal prolapse and recto-rectal intussusception. However, due to the technical
complexity of VMR, a significant learning curve has been previously described.
This paper examines the effect of proctored adoption of VMR on learning curves,
operative times, and outcomes. METHODS: A retrospective database analysis of two
district general hospitals was conducted, with inclusion of all cases performed
by two surgeons since first adoption of the procedure in 2007-2015. Operative
time, length of stay, and in-hospital complications were evaluated, with learning
curves assessed using cumulative sum curves. RESULTS: Three hundred and eleven
patients underwent VMR during the study period and were included for analysis.
Patients were near-equally distributed between surgeons (surgeon A: n = 151,
surgeon B, n = 160) with no significant differences between gender, age, or ASA
grade. In-hospital morbidity was 3.2 %, with 0 % mortality. Cumulative sum curve
analysis suggested a change point of between 25 and 30 cases based on operative
times and length of stay and was similar between both surgeons. No significant
change point was seen for morbidity or mortality. CONCLUSION: VMR is an effective
and safe treatment for rectal prolapse. Surgeons in this study were proctored
during the adoption process by another surgeon experienced in VMR; this may
contribute to increased safety and abbreviated learning curve. In the context of
proctored adoption, this study estimates a learning curve of 25-30 cases, without
detrimental impact on patient outcomes.
PMID- 27495332
TI - Efficacy of transoral incisionless fundoplication (TIF) for the treatment of
GERD: a systematic review with meta-analysis.
AB - BACKGROUND: The efficacy of transoral incisionless fundoplication (TIF) performed
with the EsophyX device (Redmond, Washington, USA) and its long-term outcomes in
gastresophageal reflux disease (GERD) are debated. We, therefore, performed a
systematic review with meta-analysis of studies evaluating the role of TIF in
GERD. METHODS: A systematic search of EMBASE, SCOPUS, PubMed, and the Cochrane
Library Central was performed. All original studies reporting outcomes in GERD
patients who underwent TIF were identified. Only randomized controlled trials
(RCTs) evaluating the efficacy of TIF, and prospective observational studies
reporting outcomes after TIF were included. RESULTS: A total of 18 studies (963
patients) published between 2007 and 2015 were identified, including five RCTs
and 13 prospective observational studies. The pooled relative risk of response
rate to TIF versus PPIs/sham was 2.44 (95 % CI 1.25-4.79, p = 0.0009) in RCTs in
the intention-to-treat analysis. The total number of refluxes was reduced after
TIF compared with the PPIs/sham group. The esophageal acid exposure time and acid
reflux episodes after TIF were not significantly improved. Proton-pump inhibitors
(PPIs) usage increased with time and most of the patients resumed PPIs treatment
at reduced dosage during the long-term follow-up. The total satisfaction rate
after TIF was about 69.15 % in 6 months. The incidence of severe adverse events
consisting of gastrointestinal perforation and bleeding was 2.4 %. CONCLUSIONS:
TIF is an alternative intervention in controlling GERD-related symptoms with
comparable short-term patient satisfaction. Long-term results showed decreased
efficacy with time. Patients often resume PPIs at reduced doses in the near
future.
PMID- 27495334
TI - Biomarkers of acute appendicitis: systematic review and cost-benefit trade-off
analysis.
AB - BACKGROUND: Acute appendicitis is the most common surgical emergency and can
represent a challenging diagnosis, with a negative appendectomy rate as high as
20 %. This review aimed to evaluate the clinical utility of individual biomarkers
in the diagnosis of appendicitis and appraise the quality of these studies.
METHODS: A systematic review of the literature between January 2000 and September
2015 using of PubMed, OvidMedline, EMBASE and Google Scholar was conducted.
Studies in which the diagnostic accuracy, statistical heterogeneity and
predictive ability for severity of several biomarkers could be elicited were
included. Information regarding costs and process times was retrieved from the
regional laboratory. European surgeons blinded to these reviews were
independently asked to rank which characteristics of biomarkers were most
important in acute appendicitis to inform a cost-benefit trade-off. Sensitivity
testing and the QUADAS-2 tool were used to assess the robustness of the analysis
and study quality, respectively. RESULTS: Sixty-two studies met the inclusion
criteria and were assessed. Traditional biomarkers (such as white cell count)
were found to have a moderate diagnostic accuracy (0.75) but lower costs in the
diagnosis of acute appendicitis. Conversely, novel markers (pro-calcitonin, IL 6
and urinary 5-HIAA) were found to have high process-related costs including
analytical times, but improved diagnostic accuracy. QUADAS-2 analysis revealed
significant potential biases in the literature. CONCLUSION: When assessing
biomarkers, an appreciation of the trade-offs between the costs and benefits of
individual biomarkers is needed. Further studies should seek to investigate new
biomarkers and address concerns over bias, in order to improve the diagnosis of
acute appendicitis.
PMID- 27495335
TI - Clinical impact of laparoscopic hepatectomy: technical and oncological
viewpoints.
AB - The objective of this study was to assess the clinical impact of laparoscopic
hepatectomy from technical and oncological viewpoints through the consecutive 5
year experience of an expert team. The subjects consisted of 491 consecutive
hepatectomies performed over the course of 5 years. A total of 190 hepatectomies
(38.6 %) were performed laparoscopically, and the remaining 301 (61.4 %) were
open hepatectomies. Chronological trends of operative procedures and their
indications were evaluated, and patients with hepatocellular carcinoma (HCC) were
analyzed from an oncological viewpoint. The proportion of laparoscopic
hepatectomies performed increased significantly during the study period (from
17.6 to 49.5 %). According to chronological trends, right hepatectomy was
standardized using consecutive steps after minor hepatectomy, left lateral
sectionectomy, and left hepatectomy were standardized. The proportion of
laparoscopic hepatectomies performed for HCC increased from 21.4 to 71.0 %. No
significant difference was observed in the proportion of major hepatectomies
performed for HCC between the open and laparoscopy groups (50.6 vs. 48.6 %, p =
0.8053), whereas that of anatomical segmentectomy for HCC was significantly lower
in the laparoscopy group (28.7 vs. 11.1 %, p = 0.0064). All laparoscopic
anatomical segmentectomies were of segments 5 and 6, and there was no
segmentectomy of posterosuperior lesions. The present study shows the consecutive
technical developmental processes for minor hepatectomy, left lateral
sectionectomy, left hepatectomy, and right hepatectomy without compromising
oncological principles. Laparoscopic anatomical segmentectomy for posterosuperior
lesions may be the most technically demanding procedure, requiring individualized
standardization.
PMID- 27495336
TI - Postoperative complications as an independent risk factor for recurrence after
laparoscopic ventral hernia repair: a prospective study of 417 patients with long
term follow-up.
AB - BACKGROUND: Laparoscopic ventral hernia repair (LVHR) has become widely used.
This study evaluates outcomes of LVHR, with particular reference to
complications, seromas, and long-term recurrence. METHODS: A review of a
prospective database of consecutive patients undergoing LVHR with intraperitoneal
onlay mesh (IPOM) was performed at a single institution. Patient's
characteristics, surgical procedures, and postoperative outcomes were analyzed
and related to long-term recurrence. RESULTS: From 2005 to 2014, 417 patients
underwent LVHR. Mean age and body mass index (BMI) were 54 years and 31 kg/m2.
Mesh fixation was carried out with transfascial sutures, completed with
absorbable tacks (72 %), metal tacks (24 %), or intraperitoneal sutures (4 %).
Intraoperative complications occurred in three patients. Overall morbidity
included 8.25 % of minor complications and 2.5 % of major complications without
mortality. The overall recurrence rate was 9.8 %. Median time for recurrence was
15.3 months (3-72) and median follow-up was 31.6 months (8-119). In a
multivariate analysis, previous interventions (OR 1.44; CI 1.15-1.79; p = 0.01),
postoperative complications (OR 2.57; CI 1.09-6.03; p = 0.03), and Clavien-Dindo
score >2 (OR 1.43; CI 1.031-1.876; p = 0.02) appeared as independent prognostic
factors of recurrence. Minor complications were associated with 14.7 % of
recurrence and major complications with 30 % of recurrence. Emergency LVHR (6 %)
did not increase the rate of complications. Overall seroma rate was 18.7 %, with
1.4 % of persisting or complicated seroma. BMI (OR 1.05; CI 1.01-1.08; p = 0.026)
and vascular surgery history (OR 5.74; CI 2.11-15.58; p < 0.001) were independent
predictive factors for seroma. Recurrence did not appear to be related to seroma.
CONCLUSION: LVHR combines the benefits of laparoscopy with those of mesh repair.
Seroma formation should no longer be considered as a complication. It is
spontaneously regressive in most cases. Postoperative complications and their
degree of severity appear to be independent prognostic factors for recurrence,
which can be limited with a standardized technique and may make IPOM-LVHR a
reference procedure.
PMID- 27495337
TI - Robotic partial nephrectomy performed with Airseal versus a standard CO2 pressure
pneumoperitoneum insufflator: a prospective comparative study.
AB - BACKGROUND: Airseal represents a new generation of valveless and barrier-free
surgical trocars that enable a stable pneumoperitoneum with continuous smoke
evacuation and carbon dioxide (CO2) recirculation during surgery. The aim of the
current study was to evaluate the potential advantages of the Airseal compared to
a standard CO2 insufflator in the field of robotic partial nephrectomy (RPN).
METHODS: Between October 2012 and April 2015, two cohorts of 122 consecutive
patients with clinically localized renal cell carcinoma underwent RPN by a single
surgeon, with the use of a standard CO2 pressure insufflator (Group A, 55
patients) or Airseal (Group B, 67 patients) and were prospectively compared.
RESULTS: The two groups were similar in baseline, preoperative characteristics.
The mean dimension of the lesion, as evaluated by contrast-enhanced CT scan, was
30 (median 28; IQR 2) and 39 mm (median 40; IQR 2) for Groups A and B,
respectively (p < 0.05). The complexity of the treated tumors was similar, as
indicated by the mean RENAL nephrometry score. Positive surgical margins rate was
similar in both groups (3.6 vs 4.5 %, p = 0.8) as well as the need for
postoperative blood transfusion (9.1 vs 4.5 %, p = 0.3) and the development of
postoperative acute kidney injury (16.4 vs 10.4 %, p = 0.3). Mean operative time
and warm ischemia time were significantly shorter in Group B. Moreover, a
significant increase in the cases performed as "zero ischemia" was observed in
Group B (7.3 vs 30 %, p < 0.01). CONCLUSIONS: This is the first study comparing
the Airseal with a standard CO2 insufflator system in the field of the RPN. The
preliminary outcomes in terms of overall operative time, warm ischemia time and
cases performed as "zero ischemia" are better with respect to standard
insufflators. The feasibility, safety and efficacy of combining laser tumor
enucleation with the valve-free insufflation systems should be evaluated.
PMID- 27495338
TI - Risk factors for lymph node metastasis and long-term outcomes of patients with
early gastric cancer after non-curative endoscopic submucosal dissection.
AB - BACKGROUND: The long-term outcomes after non-curative gastric endoscopic
submucosal dissection (ESD) are still unknown. We aimed to clarify the
pathological risk factors for lymph node metastasis (LNM) of early gastric cancer
(EGC) and the long-term outcomes among patients who were judged to have had non
curative ESD. METHODS: From September 2002 to December 2012, 506 patients who
were judged to have had non-curative gastric ESD were enrolled and classified
into two groups: (1) those who subsequently underwent additional surgical
resection (surgical group, n = 323) and (2) those followed up without additional
surgical resection (nonsurgical group, n = 183). We analyzed pathological risk
factors for LNM of EGC in the surgical group. Additionally, we compared long-term
outcomes in the two groups. RESULTS: LNM was found pathologically in 9.3 % of the
surgical group (30/323) at the additional surgical resection after non-curative
ESD. In the multivariate logistic regression analysis, lymphovascular invasion
(LVI) was an independent risk factor for LNM in the surgical group (odds ratio
8.57, 95 % confidence interval 2.76-38.14, P < 0.0001). The 5-year cause-specific
survival rate was similar in the surgical and nonsurgical groups (98.7 and 96.5
%, respectively; log-rank test, P = 0.07). In contrast, the 5-year cause-specific
survival rate of patients with LVI in the surgical group was better than that in
the nonsurgical group (98.2 and 79.1 %, respectively; log-rank test, P < 0.0001).
CONCLUSIONS: A detailed assessment of LVI is essential to the pathological
evaluation of endoscopically resected specimens. An additional surgical resection
should be strongly recommended for patients with LVI.
PMID- 27495339
TI - Preventing anastomotic complications: early results of laparoscopic gastric
devascularization two weeks prior to minimally invasive esophagectomy.
AB - BACKGROUND: Laparoscopic gastric devascularization (LGD) is an innovative method
to improve gastric conduit perfusion and improve anastomotic healing following
esophagectomy. This study reports our early experience with LGD performed two
weeks prior to minimally invasive esophagectomy (MIE) with intrathoracic
anastomosis. METHODS: We performed a retrospective review of all patients who
underwent LGD prior to minimally invasive Ivor Lewis esophagectomy between August
2014 and July 2015 at a large academic medical center. LGD included staging
laparoscopy with division of the short gastric vessels, left gastric artery and
coronary vein, and posterior gastric attachments. Patient demographics, comorbid
conditions, clinical stage, use of neoadjuvant chemoradiation, perioperative
events, length of hospital stay, 60-day readmission, and complications were
collected and analyzed. RESULTS: Thirty patients underwent LGD prior to minimally
invasive Ivor Lewis esophagectomy, and 21 (70 %) received neoadjuvant
chemoradiation. LGD was performed a median of 14.5 (9-42) days prior to
esophagectomy. Median operative time was 39 (18-56) minutes, and median length of
stay was 0 (0-1) days. There were no complications or readmissions following LGD.
MIE was completed laparoscopically in 93 % of patients; two patients required
conversion to an open procedure due to mediastinal inflammation following
neoadjuvant chemoradiation. Five patients (17 %) were readmitted within 60 days
of surgery: one (3 %) patient with an anastomotic leak, two (7 %) with pneumonia,
and two (7 %) with post-operative nausea and vomiting. One patient (3 %) expired
following an anastomotic leak that required reoperation, and no patients
developed an anastomotic stricture during the study period. CONCLUSIONS: LGD with
delayed esophageal resection and reconstruction can be safely performed two weeks
prior to MIE with minimal morbidity. The low rate of anastomotic leak (3 %) and
absence of anastomotic strictures in this series suggest that this approach may
successfully improve gastroesophageal anastomotic healing and reduce the rate of
anastomotic complications reported with single-stage approaches.
PMID- 27495340
TI - A new experimental model of calculous cholecystitis suitable for the evaluation
and training of minimally invasive approaches to cholecystectomy.
AB - BACKGROUND: Novel, less invasive approaches such as single-incision laparoscopic
cholecystectomy or natural orifice transluminal endoscopic surgery require
preclinical evaluation and training. Therefore, there is a need for an
experimental model closely mimicking the clinical situation. The aim of our study
was to create an experimental model of calculous cholecystitis in a large
laboratory animal and test its feasibility for the evaluation of different
techniques of cholecystectomy. METHODS: In 11 laboratory pigs, gallstones were
placed inside the gallbladder laparoscopically. Levels of inflammatory markers
leucocytes (WBC), C-reactive protein (CRP) and interleukin 6 (IL-6)-were
monitored on the postoperative days (POD) 1, 2, 3, 7 and 30. Abdominal ultrasound
was performed 2 and 4 weeks after the operation. Four weeks after the lithiasis
induction, laparoscopic cholecystectomy was performed. The control group
consisted of ten healthy animals in which a cholecystectomy was performed. The
pigs were monitored for 30 days after surgery. All removed gallbladders were
assessed histologically. RESULTS: The induction of lithiasis took 42 (35-52) min
with no morbidity and mortality. The values of WBC, CRP and IL-6 increased
significantly (vs. baseline) on POD 1, 2 and 3 (p < 0.05) and then normalised.
Ultrasonography confirmed the presence of chronic calculous cholecystitis in all
cases after 4 weeks. Laparoscopic cholecystectomy was significantly longer in
animals with lithiasis, 63 (42-91) versus 46 (31-62) min (p = 0.018).
Perioperative gallbladder wall perforation was significantly more frequent in the
model group (8/11 vs. 1/10; p = 0.04). In contrast to healthy animals, all
gallbladders with stones showed histological signs of chronic inflammation.
CONCLUSIONS: A new animal model of calculous cholecystitis was created.
Laparoscopic cholecystectomy was more technically difficult compared to operating
on a healthy gallbladder. This model may be a suitable tool for effective
preclinical training and also for the evaluation of different techniques of
cholecystectomy.
PMID- 27495341
TI - Superselective intra-arterial hepatic injection of indocyanine green (ICG) for
fluorescence image-guided segmental positive staining: experimental proof of the
concept.
AB - BACKGROUND: Intraoperative liver segmentation can be obtained by means of
percutaneous intra-portal injection of a fluorophore and illumination with a near
infrared light source. However, the percutaneous approach is challenging in the
minimally invasive setting. We aimed to evaluate the feasibility of fluorescence
liver segmentation by superselective intra-hepatic arterial injection of
indocyanine green (ICG). MATERIALS AND METHODS: Eight pigs (mean weight: 26.01 +/
5.21 kg) were involved. Procedures were performed in a hybrid experimental
operative suite equipped with the Artis Zeego(r), multiaxis robotic angiography
system. A pneumoperitoneum was established and four laparoscopic ports were
introduced. The celiac trunk was catheterized, and a microcatheter was advanced
into different segmental hepatic artery branches. A near-infrared laparoscope (D
Light P, Karl Storz) was used to detect the fluorescent signal. To assess the
correspondence between arterial-based fluorescence demarcation and liver volume,
metallic markers were placed along the fluorescent border, followed by a 3D CT
scanning, after injecting intra-arterial radiological contrast (n = 3). To assess
the correspondence between arterial and portal supplies, percutaneous intra
portal angiography and intra-arterial angiography were performed simultaneously
(n = 1). RESULTS: Bright fluorescence signal enhancing the demarcation of target
segments was obtained from 0.1 mg/mL, in matter of seconds. Correspondence
between the volume of hepatic segments and arterial territories was confirmed by
CT angiography. Higher background fluorescence noise was found after positive
staining by intra-portal ICG injection, due to parenchymal accumulation and porto
systemic shunting. CONCLUSIONS: Intra-hepatic arterial ICG injection, rapidly
highlights hepatic target segment borders, with a better signal-to-background
ratio as compared to portal vein injection, in the experimental setting.
PMID- 27495342
TI - Twenty-year experience with laparoscopic inguinal hernia repair in infants and
children: considerations and results on 1833 hernia repairs.
AB - BACKGROUND: The role of laparoscopy in pediatric inguinal hernia (IH) is still
controversial. The authors reported their twenty-year experience in laparoscopic
IH repair in children. METHODS: In a twenty-year period (1995-2015), we operated
1300 infants and children (935 boys-365 girls) with IH using laparoscopy. The
average age at surgery was 18 months (range 7 days-14 years). Body weight ranged
between 1.9 and 50 kg (average 9.3). Preoperatively all patients presented a
monolateral IH, right-sided in 781 cases (60.1 %) and left-sided in 519 (39.9 %).
We excluded patients with bilateral IH and unstable patients in which laparoscopy
was contraindicated. If the inguinal orifice diameter was >=10 mm, we performed a
modified purse string suture on peri-orificial peritoneum, in orifices <=5 mm, we
performed a N-shaped suture. RESULTS: No conversion to open surgery was reported.
In 533 cases (41 %), we found a contralateral patency of internal inguinal ring
that was always closed in laparoscopy. In 1273 cases (97.9 %), we found an
oblique external hernia; in 21 cases (1.6 %), a direct hernia; and in 6 cases
(0.5 %), a double hernia on the same side (hernia en pantaloon). We found an
incarcerated hernia in 27 patients (2 %). Average operative time was 18 min
(range 7-65). We recorded 5/1300 recurrences (0.3 %), but in the last 950
patients, we had no recurrence (0 %). We recorded 20 complications (1.5 %): 18
umbilical granulomas and two trocars scar infections, treated in outpatient
setting. CONCLUSIONS: On the basis of our twenty-year experience, we prefer to
perform IH repair in children using laparoscopy rather than inguinal approach.
Laparoscopy is as fast as inguinal approach, and it has the advantage to treat
during the same anesthesia a contralateral patency occured in about 40 % of our
cases and to treat also rare hernias in about 3 % of cases.
PMID- 27495343
TI - Risk factors associated with difficult gastric endoscopic submucosal dissection:
predicting difficult ESD.
AB - BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) is a widely
accepted treatment for superficial gastric neoplasms. Difficult ESD can lead to
complications, such as bleeding and perforation. To predict difficult ESD
procedures, we analyzed the factors associated with difficult ESD. PATIENTS AND
METHODS: The medical records of 1052 ESD procedures were retrospectively
reviewed. Difficult ESD was defined by any one of three end points: longer
procedure time (>=60 min), piecemeal resection, incomplete (R1) resection, or
gastric wall perforation. To determine the factors associated with difficult ESD,
clinical and pathologic features and endoscopic findings were analyzed. RESULTS:
The rates of en bloc resection and curative (R0) resection were 93.3 and 92.4 %,
respectively. The mean procedure time was 27.7 +/- 16.7 min. After multivariate
analysis, larger tumor size (>=20 mm) was an independent risk factor for longer
procedure time (OR 4.1, P < 0.001), for piecemeal resection (OR 2.3, P = 0.003)
and incomplete (R1) resection (OR 2.1, P = 0.005). Location of the lesion (upper
third) was an independent risk factor for longer procedure time (OR 5.8, P <
0.001), for piecemeal resection (OR 4.1, P < 0.001) and incomplete (R1) resection
(OR 4.5, P < 0.001). Submucosal fibrosis was an independent risk factor for
longer procedure time (OR 9.7, P < 0.001), for piecemeal resection (OR 2.4, P <
0.001) and incomplete (R1) resection (OR 2.6, P < 0.001). Finally, submucosal
invasive gastric cancer was an independent risk factor for piecemeal resection
(OR 2.6, P = 0.008), for perforation (OR 19.3, P = 0.001) and for incomplete (R1)
resection (OR 2.7, P = 0.001). CONCLUSIONS: Difficult ESD procedures are a
function of the lesion size and location, submucosal fibrosis, and submucosal
invasive cancer. When a difficult ESD procedure is expected, appropriate
preparations should be considered, including consultation with more experienced
endoscopists.
PMID- 27495344
TI - A prospective randomized comparison of testicular functions, sexual functions and
quality of life following laparoscopic totally extra-peritoneal (TEP) and trans
abdominal pre-peritoneal (TAPP) inguinal hernia repairs.
AB - BACKGROUND: There is very scant literature on the impact of inguinal hernia mesh
repair on testicular functions and sexual functions following open and
laparoscopic repair. The present randomized study compares TAPP and TEP repairs
in terms of testicular functions, sexual functions, quality of life and chronic
groin pain. METHODS: This study was conducted from April 2012 to October 2014. A
total of 160 patients with uncomplicated groin hernia were randomized to either
trans-abdominal pre-peritoneal (TAPP) repair or totally extra-peritoneal (TEP)
repair. Testicular functions were assessed by measuring testicular volume,
testicular hormone levels preoperatively and at 3 months postoperatively. Sexual
functions were assessed using BMSFI, and quality of life was assessed using WHO
QOL BREF scale preoperatively and at 3 and 6 months postoperatively. Chronic
groin pain was evaluated using the VAS scale at 3 months, 6 months and at 1 year.
RESULTS: The median duration of follow-up was 13 months (range 6-18 months). The
mean preoperative pain scores (p value 0.35) as well as the chronic groin pain
were similar between TEP and TAPP repairs at 3 months (p value 0.06) and 6 months
(p value 0.86). The testicular resistive index and testicular volume did not show
any significant change at follow-up of 3 months (p value 0.9) in the study
population. No significant difference was observed in testicular resistive index
and testicular volume when comparing TEP and TAPP groups at at follow-up of 3
months (p value >0.05). There was a statistically significant improvement in the
sexual drive score, erectile function and overall satisfaction over the follow-up
period following laparoscopic inguinal hernia repair. However, sexual function
improvement was similar in patients undergoing both TEP and TAPP repairs. All the
domains of quality of life in the study population showed a significant
improvement at a follow-up of 3 and 6 months. Subgroup analysis of all the
domains of quality of life in both TAPP and TEP groups showed a similar increment
as in the study population (p value <0.001); however, the mean scores of all the
domains were comparable between the two subgroups (p value >0.05), preoperatively
and 3 and 6 months follow-up. CONCLUSIONS: Laparoscopic groin hernia repair
improves the testicular functions, sexual functions and quality of life, but TEP
and TAPP repairs are comparable in terms of these long-term outcomes.
PMID- 27495345
TI - Outcomes of concomitant ventral hernia repair performed during bariatric surgery.
AB - BACKGROUND: Currently there is no consensus on management of ventral hernias
encountered during bariatric surgery (BS). This study aims to evaluate the
incidence and outcomes of concomitant ventral hernia repair (VHR) during BS at
our institution. METHODS: Patients who had concomitant VHR during BS from 2004 to
2015 were identified. Data collected included baseline demographics,
comorbidities, perioperative parameters, surgical approach and postoperative
outcomes. RESULTS: A total of 159 patients underwent concomitant VHR during the
study period at the time of BS. One hundred and one (64 %) patients were female;
median age was 53 years (IQR 45.0-60.3) and median BMI was 48.2 kg/m2 (IQR 41.6
54.1). Comorbidities included: hypertension (n = 124, 78 %), type 2 diabetes (n =
103, 65 %), hyperlipidemia (n = 100, 63 %), obstructive sleep apnea (n = 98, 62
%) and reflux disease (n = 54, 34 %). Out of 159 patients, 41 patients (26 %) had
a prior VHR. Out of 103 patients, 69 patients (67 %) had a previous abdominal
surgery. Of the concomitant VHR, 144 (91 %) were completed laparoscopically, 12
(7 %) patients were converted to open surgery and 3 (2 %) patients underwent
primary open procedures. Technique included primary suture closure in 115 (72 %)
and mesh repair in 44. Early postoperative complications (<30 days) were reported
in 16 (10 %) patients, with superficial wound infection (n = 9), bowel
obstruction (n = 2), marginal ulcer (n = 2), DVT (n = 1) and pneumonia (n = 1).
Hernia recurrence was reported in 3 patients (2 %) in the early post-op period
and in 40 patients (25 %) as a late (>30 days) complication. Surgery for
recurrent hernia was performed in 31/42 patients during follow-up. At 12-month
follow-up, median BMI and % excess weight loss were 34.2 kg/m2 (IQR 29.5-40.9)
and 59.6 % (IQR 44.9-74.8 %), respectively. CONCLUSION: Ventral hernia is a
common finding in patients undergoing BS. Both primary suture repair and mesh
repair result in acceptable results, both in terms of recurrence and
perioperative complications.
PMID- 27495346
TI - A retrospective comparison of robotic cholecystectomy versus laparoscopic
cholecystectomy: operative outcomes and cost analysis.
AB - INTRODUCTION: Robotic-assisted surgery is gaining popularity in general surgery.
Our objective was to evaluate and compare operative outcomes and total costs for
robotic cholecystectomy (RC) and laparoscopic cholecystectomy (LC). METHODS AND
PROCEDURES: A retrospective review was performed for all patients who underwent
single-procedure RC and LC from January 2011 to July 2015 by a single surgeon at
a large academic medical center. Demographics, diagnosis, perioperative
variables, postoperative complications, 30-day readmissions, and operative and
hospital costs were collected and analyzed between those patient groups. RESULTS:
A total of 237 patients underwent RC or LC, and comprised the study population.
Ninety-seven patients (40.9 %) underwent LC, and 140 patients (50.1 %) underwent
RC. Patients who underwent RC had a higher body mass index (p = 0.03), lower
rates of coronary artery disease (p < 0.01), and higher rates of chronic
cholecystitis (p < 0.01). There were lower rates of intraoperative
cholangiography (p < 0.01) and conversion to an open procedure (p < 0.01),
however longer operative times (p < 0.01) for patients in the RC group. There
were no bile duct injuries in either group, no difference in bile leak rates (p =
0.65), or need for reoperation (p = 1.000). Cost analysis of outpatient-only
procedures, excluding cases with conversion to open or use of intraoperative
cholangiography, demonstrated higher total charges (p < 0.01) and cost (p < 0.01)
and lower revenue (p < 0.01) for RC compared to LC, with no difference in total
payments (p = 0.34). CONCLUSIONS: Robotic cholecystectomy appears to be safe
although costlier in comparison with laparoscopic cholecystectomy. Further
studies are needed to understand the long-term implications of robotic
technology, the cost to the health care system, and its role in minimally
invasive surgery.
PMID- 27495349
TI - Letter: The History of the Kernohan Notch Revisited.
PMID- 27495347
TI - Robotic-assisted ventral hernia repair: a multicenter evaluation of clinical
outcomes.
AB - BACKGROUND: The open approach continues to be widely performed for ventral hernia
repair, while the minimally invasive laparoscopic approach has grown adoption
over the last decade. Recently, robotic operation was described as a new modality
due to the ease for performing intracorporeal closure of the hernia defect. This
study is one of the first multi-institutional case series evaluating robotic
assisted laparoscopic ventral hernia repairs, with the goal of describing robotic
assisted surgical techniques for ventral and incisional hernia repair and the
outcomes in teaching and community hospital settings. METHODS: Medical records of
consecutive patients (including surgeon's learning curve cases) who underwent
ventral or incisional hernia repair utilizing the da Vinci Surgical System
(Intuitive Surgical Inc, Sunnyvale CA) were retrospectively reviewed. Data
collected included preoperative history and perioperative outcomes. RESULTS: Data
for a total of 368 patients from four institutions involving five surgeons were
analyzed. They were predominantly females (60.3 %), and the mean age was 51
years. The majority of the patients were obese or morbidly obese (47.8 and 20.9
%), and 83.2 % of the patients had a history of prior abdominal operation.
Conversion rate was 0.8 %, and mean length of stay was 1 day. Total postoperative
complications rate up to 30 days was 8.4 %, of which incidence of paralytic ileus
was 2.4 %. CONCLUSION: This large case series of 368 patients demonstrates
reproducibility of safety and performance associated with robotic-assisted
ventral hernia repairs performed by five surgeons at four institutions. In
addition, the results of short term perioperative outcomes for surgeons during
their early experience for robotic-assisted cases are in the range of what is
reported in the existing published data on laparoscopic and open ventral hernia
repairs. Further comparative evidence initiatives are being pursued to determine
the benefits of robotic-assisted technique and technology for long-term and
patient-reported outcomes.
PMID- 27495348
TI - Increasing resident utilization and recognition of the critical view of safety
during laparoscopic cholecystectomy: a pilot study from an academic medical
center.
AB - BACKGROUND: Laparoscopic cholecystectomy (LC) is a commonly performed surgical
procedure; however, it is associated with an increased rate of bile duct injury
(BDI) when compared to the open approach. The critical view of safety (CVS)
provides a secure method of ductal identification to help avoid BDI. CVS is not
universally utilized by practicing surgeons and/or taught to surgical residents.
We aimed to pilot a safe cholecystectomy curriculum to demonstrate that
educational interventions could improve resident adherence to and recognition of
the CVS during LC. METHODS: Forty-three general surgery residents at Thomas
Jefferson University Hospital were prospectively studied. Fifty-one consecutive
LC cases were recorded during the pre-intervention period, while the residents
were blinded to the outcome measured (CVS score). As an intervention, a
comprehensive lecture on safe cholecystectomy was given to all residents. Fifty
consecutive LC cases were recorded post-intervention, while the residents were
empowered to "time-out" and document the CVS with a doublet photograph. Two
independent surgeons scored the videos and photographs using a 6-point scale.
Residents were surveyed pre- and post-intervention to determine objective
knowledge and self-reported comfort using a 5-point Likert scale. RESULTS: In the
18-week study period, 101 consecutive LCs were adequately captured and included
(51 pre-intervention, 50 post-intervention). Patient demographics and clinical
data were similar. The mean CVS score improved from 2.3 to 4.3 (p < 0.001). The
number of videos with CVS score >4 increased from 15.7 to 52 % (p < 0.001). There
was strong inter-observer agreement between reviewers. The pre- and post
intervention questionnaire response rates were 90.7 and 83.7 %, respectively. A
greater number of residents correctly identified all criteria of the CVS post
intervention (41-93 %, p < 0.001) and offered appropriate bailout techniques (77
94 %, p < 0.001). Residents strongly agreed that the CVS education should be
included in general surgery residency curriculum (mean Likert score = 4.71, SD =
0.54). Residents also agreed that they are more comfortable with their LC skills
after the intervention (4.27, sigma = 0.83). CONCLUSION: The combination of
focused education along with intraoperative time-out significantly improved CVS
scores and knowledge during LC in our institution.
PMID- 27495350
TI - Design Considerations of a Fiber Optic Pressure Sensor Protective Housing for
Intramuscular Pressure Measurements.
AB - Intramuscular pressure (IMP), defined as skeletal muscle interstitial fluid
pressure, reflects changes in individual muscle tension and may provide crucial
insight into musculoskeletal biomechanics and pathologies. IMP may be measured
using fiber-optic fluid pressure sensors, provided the sensor is adequately
anchored to and shielded from surrounding muscle tissue. Ineffective anchoring
enables sensor motion and inadequate shielding facilitates direct sensor-tissue
interaction, which result in measurement artifacts and force-IMP dissociation.
The purpose of this study was to compare the effectiveness of polyimide and
nitinol protective housing designs to anchor pressure sensors to muscle tissue,
prevent IMP measurement artifacts, and optimize the force-IMP correlation.
Anchoring capacity was quantified as force required to dislodge sensors from
muscle tissue. Force-IMP correlations and non-physiological measurement artifacts
were quantified during isometric muscle activations of the rabbit tibialis
anterior. Housing structural integrity was assessed after both anchoring and
activation testing. Although there was no statistically significant difference in
anchoring capacity, nitinol housings demonstrated greater structural integrity
and superior force-IMP correlations. Further design improvements are needed to
prevent tissue accumulation in the housing recess associated with artificially
high IMP measurements. These findings emphasize fundamental protective housing
design elements crucial for achieving reliable IMP measurements.
PMID- 27495351
TI - Do Selective Serotonin Reuptake Inhibitors (SSRIs) Cause Fractures?
AB - Recent meta-analyses report a 70 % increase in fracture risk in selective
serotonin reuptake inhibitor (SSRI) users compared to non-users; however,
included studies were observational and limited in their ability to establish
causality. Here, we use the Bradford Hill criteria to explore causality between
SSRIs and fractures. We found a strong, consistent, and temporal relationship
between SSRIs and fractures, which appears to follow a biological gradient.
However, specificity and biological plausibility remain concerns. In terms of
specificity, the majority of available data have limitations due to either
confounding by indication or channeling bias. Self-controlled case series address
some of these limitations and provide relatively strong observational evidence
for a causal relationship between SSRIs and fracture. In doing so, they suggest
that falls contribute to fractures in SSRI users. Whether there are also
underlying changes in skeletal properties remains unresolved. Initial studies
provide some evidence for skeletal effects of SSRIs; however, the pathways
involved need to be established before biological plausibility can be accepted.
As the link between SSRIs and fractures is based on observational data and not
evidence from prospective trials, there is insufficient evidence to definitively
determine a causal relationship and it appears premature to label SSRIs as a
secondary cause of osteoporosis. SSRIs appear to contribute to fracture-inducing
falls, and addressing any fall risk associated with SSRIs may be an efficient
approach to reducing SSRI-related fractures. As fractures stemming from SSRI
induced falls are more likely in individuals with compromised bone health, it is
worth considering bone density testing and intervention for those presenting with
risk factors for osteoporosis.
PMID- 27495352
TI - Characteristics and Methodological Quality of Meta-Analyses on Hypertension
Treatments-A Cross-Sectional Study.
AB - Methodological quality of meta-analyses on hypertension treatments can affect
treatment decision-making. The authors conducted a cross-sectional study to
investigate the methodological quality of meta-analyses on hypertension
treatments. One hundred and fifty-eight meta-analyses were identified. Overall,
methodological quality was unsatisfactory in the following aspects: comprehensive
reporting of financial support (1.9%), provision of included and excluded lists
of studies (22.8%), inclusion of grey literature (27.2%), and inclusion of
protocols (32.9%). The 126 non-Cochrane meta-analyses had poor performance on
almost all the methodological items. Non-Cochrane meta-analyses focused on
nonpharmacologic treatments were more likely to consider scientific quality of
included studies when making conclusions. The 32 Cochrane meta-analyses generally
had good methodological quality except for comprehensive reporting of the sources
of support. These results highlight the need for cautious interpretation of these
meta-analyses, especially among physicians and policy makers when guidelines are
formulated. Future meta-analyses should pay attention to improving these
methodological aspects.
PMID- 27495353
TI - No more neglect of helminths and HIV.
PMID- 27495354
TI - Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania:
a prospective cohort study.
AB - BACKGROUND: The past decades have seen an ongoing controversial debate about
whether the immune activation induced by helminths has an effect on the
susceptibility of individuals to HIV. In view of this, we assessed the effect of
lymphatic filariasis, a chronic helminth disease elicited by Wuchereria
bancrofti, on HIV incidence in southwest Tanzania. METHODS: In this population
based cohort study, we enrolled a geographically stratified randomly chosen
sample of about 10% of the households in nine distinct sites in southwest
Tanzania. All household members present were followed up and tested for HIV and
circulating filarial antigen, an indicator of W bancrofti adult worm burden. Our
main outcome of interest was HIV incidence in participants with or without
lymphatic filariasis. FINDINGS: Between May 29, 2006, and June 16, 2011, we
enrolled 4283 households with roughly 18 000 participants. Of these, 2699
individuals from Kyela district participated in at least one round of the EMINI
study. In the 1055 initially HIV-negative adolescents and adults with clearly
defined lymphatic filariasis status, 32 new HIV infections were observed in 2626
person-years. HIV incidence in lymphatic filariasis-positive participants (1.91
cases per 100 person-years) was significantly higher than the incidence in
lymphatic filariasis-negative participants (0.80 cases per 100 person-years). The
age-adjusted and sex-adjusted incidence rate ratio was 2.17 (95% CI 1.08-4.37,
p=0.0300). Lymphatic filariasis status remained an independent and significantly
relevant risk factor for HIV infection when controlled for other known risk
factors such as sexual behaviour and socioeconomic factors. INTERPRETATION: To
our knowledge, this is the first prospective study demonstrating a significantly
increased risk of acquiring HIV for lymphatic filariasis-infected individuals.
Immunological studies and interventional treatment studies that eliminate the
adult worms and not only the microfilariae are needed to follow up on the results
presented. FUNDING: European Union as part of EuropAid; German Federal Ministry
of Education and Research; German Center for Infection Research.
PMID- 27495355
TI - Neoechinulin A induced memory improvements and antidepressant-like effects in
mice.
AB - Neoechinulin A is an isoprenyl indole alkaloid that exhibits scavenging,
neurotrophic factor-like, and anti-apoptotic activities. However, the
effectiveness of neoechinulin A in animal models of disease has not yet been
explored. In the present study, we investigated the effects of neoechinulin A on
memory impairment in lipopolysaccharide (LPS)-treated mice and its antidepressant
like effects in mice. In the Y-maze test, the intracerebroventicular (i.c.v.)
administration of LPS (10MUg/mouse) significantly decreased spontaneous
alternation behavior, which was prevented by the prior administration of
neoechinulin A (300ng/mouse, i.c.v.). None of the treatments altered the
locomotor activity of mice. Moreover, the administration of neoechinulin A
decreased the immobility time in the forced-swim test or tail suspension test,
which was prevented by the prior administration of WAY100635 (an antagonist of 5
HT1A receptors) and parachlorophenylalanine (an inhibitor of tryptophan
hydroxylase). These results suggest that neoechinulin A improves memory functions
in LPS-treated mice, and also exerts antidepressant-like effects through changes
in the 5-HT system.
PMID- 27495356
TI - Error-related brain activity in youth and young adults before and after treatment
for generalized or social anxiety disorder.
AB - Increased error monitoring, as measured by the error-related negativity (ERN),
has been shown to persist after treatment for obsessive-compulsive disorder in
youth and adults; however, no previous studies have examined the ERN following
treatment for related anxiety disorders. We used a flanker task to elicit the ERN
in 28 youth and young adults (8-26years old) with primary diagnoses of
generalized anxiety disorder (GAD) or social anxiety disorder (SAD) and 35
healthy controls. Patients were assessed before and after treatment with
cognitive-behavioral therapy (CBT) or selective serotonin reuptake inhibitors
(SSRI), and healthy controls were assessed at a comparable interval. The ERN
increased across assessments in the combined sample. Patients with SAD exhibited
an enhanced ERN relative to healthy controls prior to and following treatment,
even when analyses were limited to SAD patients who responded to treatment.
Patients with GAD did not significantly differ from healthy controls at either
assessment. Results provide preliminary evidence that enhanced error monitoring
persists following treatment for SAD in youth and young adults, and support
conceptualizations of increased error monitoring as a trait-like vulnerability
that may contribute to risk for recurrence and impaired functioning later in
life. Future work is needed to further evaluate the ERN in GAD across
development, including whether an enhanced ERN develops in adulthood or is most
apparent when worries focus on internal sources of threat.
PMID- 27495357
TI - To what extent is it possible to dissociate the anxiolytic and sedative/hypnotic
properties of GABAA receptors modulators?
AB - The relatively common view indicates a possible dissociation between the
anxiolytic and sedative/hypnotic properties of benzodiazepines (BZs). Indeed,
GABAA receptor (GABAAR) subtypes have specific cerebral distribution in distinct
neural circuits. Thus, GABAAR subtype-selective drugs may be expected to perform
distinct functions. However, standard behavioral test assays provide limited
direction towards highlighting new action mechanisms of ligands targeting
GABAARs. Automated behavioral tests, lack sensitivity as some behavioral
characteristics or subtle behavioral changes of drug effects or that are not
considered in the overall analysis (Ohl et al., 2001) and observation-based
analyses are not always performed. In addition, despite the use of genetically
engineered mice, any possible dissociation between the anxiolytic and sedative
properties of BZs remains controversial. Moreover, the involvement the different
subtypes of GABAAR subtypes in the anxious behavior and the mechanism of action
of anxiolytic agents remains unclear since there has been little success in the
pharmacological investigations so far. This raises the question of the
involvement of the different subunits in anxiolytic-like and/or sedative effects;
and the actual implication of these subunits, particularly, alpha-subunits in the
modulation of sedation and/or anxiety-related disorders. This present review was
prompted by several conflicting studies on the degree of involvement of these
subunits in anxiolytic-like and/or sedative effects. To this end, we explored the
GABAergic system, particularly, the role of different subunits containing
synaptic GABAARs. We report herein the targeting gene encoding the different
subunits and their contribution in anxiolytic-like and/or sedative actions, as
well as, the mechanism underlying tolerance to BZs.
PMID- 27495358
TI - Mean kurtosis alterations of cerebral white matter in patients with schizophrenia
revealed by diffusion kurtosis imaging.
AB - INTRODUCTION: Diffusion kurtosis imaging can provide a better understanding of
microstructural white matter (WM) changes where crossing fibers exist, compared
with conventional diffusion tensor imaging. Here, we aimed to examine the
differences of mean kurtosis (MK) and fractional anisotropy (FA) values between
patients with schizophrenia and control subjects using voxel-based analysis
(VBA). Additionally, we examined the correlation between these values and
severity of clinical symptoms in patients with schizophrenia. METHODS: MK and FA
values were acquired with a 3.0T scanner from 31 patients with schizophrenia and
31 age-, handedness-, and sex-matched healthy controls. VBA was used to compare
the MK and FA maps of the patients with schizophrenia and healthy controls. We
also performed a correlation analysis between the MK and FA values of the regions
with significant differences and the positive and negative syndrome scale scores
in patients with schizophrenia. RESULTS: Compared to FA values, voxels with MK
decrease were more widespread across bilateral cerebral the WM of patients with
schizophrenia. The MK values of left superior longitudinal fasciculus were
significantly negatively correlated with the severity of positive symptoms (r=
0.451, P=0.011). There was no significant correlation between MK and FA values
and other clinical variables. CONCLUSION: The diffusion kurtosis indices are
suitable for evaluating altered WM structures in the human brain as they may
detect white matter alterations of crossing fibers alterations of WM in
schizophrenia and assess the clinical state of patients.
PMID- 27495359
TI - Reply: Evolution and vascular calcification.
PMID- 27495360
TI - The progression of electrophysiologic abnormalities during epileptogenesis after
experimental traumatic brain injury.
AB - OBJECTIVE: Posttraumatic epilepsy (PTE) accounts for 20% of acquired epilepsies.
Experimental models are important for studying epileptogenesis. We previously
reported that repetitive high-frequency oscillations with spikes (rHFOSs) occur
early after lateral fluid percussion injury (FPI) and may be a biomarker for PTE.
The objective of this study was to use multiple electrodes in rat hippocampal and
neocortical regions to describe the long-term electroencephalographic and
behavioral evolution of rHFOSs and epileptic seizures after traumatic brain
injury (TBI). METHODS: Adult male rats underwent mild, moderate, or severe FPI or
sham injury followed by video-electroencephalography (EEG) recordings with a
combination of 16 neocortical and hippocampal electrodes at an early,
intermediate, or late time-point after injury, up to 52 weeks. Recordings were
analyzed for the presence of rHFOSs and seizures. RESULTS: Analysis was done on
28 rats with FPI and 7 shams. Perilesional rHFOSs were recorded in significantly
more rats after severe (70.3%) than mild (20%) injury or shams (14.3%). Frequency
of occurrence was significantly highest in the early (10.8/h) versus late group
(3.2/h). Late focal seizures originating from the same electrodes were recorded
in significantly more rats in the late (87.5%) versus early period (22.2%),
occurring almost exclusively in injured rats. Seizure duration increased
significantly over time, averaging 19 s at the beginning of the early period and
27 s at the end of the late period. Seizure frequency also increased
significantly over time, from 4.4 per week in the early group to 26.4 per week in
the late group. Rarely, rats displayed early seizures or generalized seizures.
SIGNIFICANCE: FPI results in early rHFOSs and later spontaneous focal seizures
arising from peri-lesional neocortex, supporting its use as a model for PTE.
Epilepsy severity increased over time and was related to injury severity. The
association between early rHFOSs and later focal seizures suggests that rHFOSs
may be a potential noninvasive biomarker of PTE.
PMID- 27495361
TI - Candida virulence and ethanol-derived acetaldehyde production in oral cancer and
non-cancer subjects.
AB - OBJECTIVES: To compare biofilm-forming ability, hydrolytic enzymes and ethanol
derived acetaldehyde production of oral Candida isolated from the patients with
oral cancer and matched non-oral cancer. MATERIAL AND METHODS: Fungal biofilms
were grown in RPMI-1640 medium, and biofilm mass and biofilm activity were
assessed using crystal violet staining and XTT salt reduction assays,
respectively. Phospholipase, proteinase, and esterase production were measured
using agar plate method, while fungal acetaldehyde production was assessed via
gas chromatography. RESULTS: Candida isolated from patients with oral cancer
demonstrated significantly higher biofilm mass (P = 0.031), biofilm metabolic
activity (P < 0.001), phospholipase (P = 0.002), and proteinase (P = 0.0159)
activity than isolates from patients with non-oral cancer. High ethanol-derived
acetaldehyde-producing Candida were more prevalent in patients with oral cancer
than non-oral cancer (P = 0.01). In univariate regression analysis, high biofilm
mass (P = 0.03) and biofilm metabolic activity (P < 0.001), high phospholipase (P
= 0.003), and acetaldehyde production ability (0.01) were significant risk
factors for oral cancer; while in the multivariate regression analysis, high
biofilm activity (0.01) and phospholipase (P = 0.01) were significantly positive
influencing factors on oral cancer. CONCLUSION: These data suggest a significant
positive association between the ability of Candida isolates to form biofilms, to
produce hydrolytic enzymes, and to metabolize alcohol to acetaldehyde with their
ability to promote oral cancer development.
PMID- 27495362
TI - Perspectives on hyperpolarised solution-state magnetic resonance in chemistry.
AB - This perspective article reviews some of the recent developments in the field of
hyperpolarisation, with a focus on solution-state NMR spectroscopy of small
molecules. Two techniques are considered in more detail, dissolution dynamic
nuclear polarisation (D-DNP) and signal amplification by reversible exchange
(SABRE). Some of the opportunities and challenges for applications of
hyperpolarised solution-state magnetic resonance in chemistry are discussed.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27495364
TI - Corrigendum to "Multiple forms of metaplasticity at a single hippocampal synapse
during late postnatal development" [Dev. Cogn. Sci. 12C (2015) 145-154].
PMID- 27495363
TI - A case-control study of innate immunity pathway gene polymorphisms in Puerto
Ricans reveals association of toll-like receptor 2 +596 variant with asthma.
AB - BACKGROUND: For many years, African Dust Storms (ADE) has been thought to be
associated with high prevalence of asthma in Puerto Rico (PR). Endotoxins (ENX)
have been associated with ADE particulate matter (PM) and are known to promote
pro-inflammatory responses in lung cells of susceptible individuals through the
Toll-like receptor (TLR2/4) signaling pathways. Genetic variants are plausible
contributors to such susceptibility. Therefore, we have evaluated a series of
nine single nucleotide polymorphisms (SNPs) in TLR genes, which have been
correlated positive and negatively to asthma prevalence and/or risk, in the
Puerto Rican asthmatic population. METHODS: The following SNPs were evaluated in
62 asthmatics and 61 controls through Taqman(r) Real Time PCR Assay: TLR4
(+896A/G, +1196C/T, -6687A/G); TLR2 (+596C/T, -16934 T/A, +399A/G, +1349C/T) and
CD14 (-159C/T, +1188C/G). Genotypes were assessed for asthma association
employing an odds ratio (OR) analysis. RESULTS: Minor allele frequencies (n =
123) were determined for those variants as 0.07, 0.06, 0.35, 0.35, 0.37, 0.29,
0.04, 0.35 and 0.11, respectively. Two (+596C/T, +399A/G) TLR2 SNPs showed to be
more represented in the asthmatic group by 89 % and 65 %, respectively. TLR4 SNP
+896A/G analysis revealed only 1 G/G genotype (2 %) on the asthmatic group. The
CD14 SNPs were similarly represented in the Puerto Rican population. Only the
TLR2 +596 SNP was found to be significantly associated to asthma (OR = 3.24 for
CT, 2.71 for TT) and particularly to females. CONCLUSIONS: The identification of
TLR SNPs will reveal potential candidates for gene-environment interactions in
Puerto Ricans. As far as we know this is the first study to evaluate this type of
TLR gene polymorphisms in Puerto Rican asthmatics, contributing to the current
knowledge in the Hispanic population.
PMID- 27495365
TI - Corrigendum to "Investigation into omocysteine, vitamin E and malondialdehyde as
indicators of successful artificial insemination in synchronized buffalo cows
(Bubalus bubalis)" [Res. Vet. Sci. Volume 104, February 2016, Pages 100-105].
PMID- 27495366
TI - Solvent-assisted dispersive solid-phase extraction: A sample preparation method
for trace detection of diazinon in urine and environmental water samples.
AB - In this research, a sample preparation method termed solvent-assisted dispersive
solid-phase extraction (SA-DSPE) was applied. The used sample preparation method
was based on the dispersion of the sorbent into the aqueous sample to maximize
the interaction surface. In this approach, the dispersion of the sorbent at a
very low milligram level was received by inserting a solution of the sorbent and
disperser solvent into the aqueous sample. The cloudy solution created from the
dispersion of the sorbent in the bulk aqueous sample. After pre-concentration of
the diazinon, the cloudy solution was centrifuged and diazinon in the sediment
phase dissolved in ethanol and determined by gas chromatography-flame ionization
detector. Under the optimized conditions (pH of solution=7.0, Sorbent:
benzophenone, 2%, Disperser solvent: ethanol, 500MUL, Centrifuge: centrifuged at
4000rpm for 3min), the method detection limit for diazinon was 0.2, 0.3, 0.3 and
0.3MUgL(-1) for distilled water, lake water, waste water and urine sample,
respectively. Furthermore, the pre-concentration factor was 363.8, 356.1, 360.7
and 353.38 in distilled water, waste water, lake water and urine sample,
respectively. SA-DSPE was successfully used for trace monitoring of diazinon in
urine, lake and waste water samples.
PMID- 27495367
TI - Separation of parent homopolymers from polystyrene and poly(ethylene oxide) based
block copolymers by liquid chromatography under limiting conditions of desorption
3. Study of barrier efficiency according to block copolymers' chemical
composition.
AB - Liquid Chromatography under Limiting Conditions of Desorption (LC LCD) is a
powerful separation tool for multicomponent polymer systems. This technique is
based on a barrier effect of an appropriate solvent, which is injected in front
of the sample, and which decelerates the elution of selected macromolecules. In
this study, the barrier effects have been evaluated for triblock copolymers
polystyrene-b-poly(ethylene oxide)-b-polystyrene (PS-b-PEO-b-PS) according to the
content of polystyrene (wt% PS) and PEO-block molar mass. PS-b-PEO-b-PS samples
were prepared by Atom Transfer Radical Polymerization (ATRP). The presence of
respective parent homopolymers was investigated by applying optimized LC LCD
conditions. It was found that the barrier composition largely affects the
efficiency of separation and it ought to be adjusted for particular composition
range of block copolymers.
PMID- 27495368
TI - A comparative evaluation of different ionic liquids for arsenic species
separation and determination in wine varietals by liquid chromatography - hydride
generation atomic fluorescence spectrometry.
AB - The application of different ionic liquids (ILs) as modifiers for chromatographic
separation and determination of arsenite [As(III)], arsenate [As(V)],
dimethylarsonic acid (DMA) and monomethylarsonic acid (MMA) species in wine
samples, by reversed-phase high performance liquid chromatography coupled to
hydride generation atomic fluorescence spectrometry detection (RP-HPLC-HG-AFS)
was studied in this work. Several factors influencing the chromatographic
separation of the As species, such as pH of the mobile phase, buffer solution
concentration, buffer type, IL concentration and length of alkyl groups in ILs
were evaluated. The complete separation of As species was achieved using a C18
column in isocratic mode with a mobile phase composed of 0.5% (v/v) 1-octyl-3
methylimidazolium chloride ([C8mim]Cl) and 5% (v/v) methanol at pH 8.5. A
multivariate methodology was used to optimize the variables involved in AFS
detection of As species after they were separated by HPLC. The ILs showed
remarkable performance for the separation of As species, which was obtained
within 18min with a resolution higher than 0.83. The limits of detection for
As(III), As(V), MMA and DMA were 0.81, 0.89, 0.62 and 1.00MUg As L(-1). The
proposed method was applied for As speciation analysis in white and red wine
samples originated from different grape varieties.
PMID- 27495369
TI - Comprehensive profiling of ribonucleosides modification by affinity zirconium
oxide-silica composite monolithic column online solid-phase microextraction -
Mass spectrometry analysis.
AB - More than 140 modified ribonucleosides have been identified in RNA. Determination
of endogenous modified ribonucleosides in biological fluids may serve as non
invasive disease diagnostic strategy. However, detection of the modified
ribonucleosides in biological fluids is challenging, especially for the low
abundant modified ribonucleosides due to the serious matrix interferences of
biological fluids. Here, we developed a facile preparation strategy and
successfully synthesized zirconium oxide-silica (ZrO2/SiO2) composite capillary
monolithic column that exhibited excellent performance for the selective
enrichment of cis-diol-containing compounds. Compared with the boronate-based
affinity monolith, the ZrO2/SiO2 monolith showed ~2 orders of magnitude higher
extraction capacity and can be used under physiological pH (pH 6.5-7.5). Using
the prepared ZrO2/SiO2 composite monolith as the trapping column and reversed
phase C18 column as the analytical column, we further established an online solid
phase microextraction (SPME) in combination with liquid chromatography-mass
spectrometry (online SPME-LC-MS/MS) analysis for the comprehensive profiling of
ribonucleosides modification in human urine. Our results showed that 68 cis-diol
containing ribosylated compounds were identified in human urine, which is, to the
best of our knowledge, the highest numbers of cis-diol-containing compounds were
determined in a single analysis. It is worth noting that four modified
ribonucleosides were discovered in the human urine for the first time. In
addition, the quantification results from the pooled urine samples showed that
compared to healthy controls, the contents of sixteen ribose conjugates in the
urine of gastric cancer, eleven in esophagus cancer and seven in lymphoma
increased more than two folds. Among these ribose conjugates, four ribose
conjugates increased more than two folds in both gastric cancer and esophagus
cancer; three ribose conjugates increased more than two folds in both gastric
cancer and lymphoma; one ribose conjugate increased more than two folds in both
esophagus cancer and lymphoma. The developed analytical method provides a good
platform to study the modified ribonucleosides in human body fluids.
PMID- 27495370
TI - Separation of pigment formulations by high-performance thin-layer chromatography
with automated multiple development.
AB - Food packaging is designed to provide sufficient protection for the respective
filling, legally binding information for the consumers like nutritional facts or
filling information, and an attractive appearance to promote the sale. For
quality and safety of the package, a regular quality control of the used printing
materials is necessary to get consistently good print results, to avoid migration
of undesired ink components into the food and to identify potentially faulty ink
batches. Analytical approaches, however, have hardly been considered for quality
assurance so far due to the lack of robust, suitable methods for the analysis of
rarely soluble pigment formulations. Thus, a simple and generic high-performance
thin-layer chromatography (HPTLC) method for the separation of different colored
pigment formulations was developed on HPTLC plates silica gel 60 by automated
multiple development. The gradient system provided a sharp resolution for
differently soluble pigment constituents like additives and coating materials.
The results of multi-detection allowed a first assignment of the differently
detectable bands to particular chemical substance classes (e.g., lipophilic
components), enabled the comparison of different commercially available pigment
batches and revealed substantial variations in the composition of the batches.
Hyphenation of HPTLC with high resolution mass spectrometry and infrared
spectroscopy allowed the characterization of single unknown pigment constituents,
which may partly be responsible for known quality problems during printing. The
newly developed, precise and selective HPTLC method can be used as part of
routine quality control for both, incoming pigment batches and monitoring of
internal pigment production processes, to secure a consistent pigment composition
resulting in consistent ink quality, a faultless print image and safe products.
Hyphenation of HPTLC with the A. fischeri bioassay gave first information on the
bioactivity or rather on the toxicological potential of different compounds of
the pigment formulations. The results of the bioassay might be helpful to choose
pigment compositions that provide both, a high printing quality but at the same
time guarantee a high consumer safety, especially in regard to smaller pigment
components, which tend to migrate through the packaging.
PMID- 27495371
TI - Simultaneous quantitation of trace level hydrazine and acetohydrazide in
pharmaceuticals by benzaldehyde derivatization with sample 'matrix matching'
followed by liquid chromatography-mass spectrometry.
AB - Hydrazine and acetohydrazide are potential genotoxins and therefore need to be
controlled in APIs and drug products to ppm levels for patient safety in cases
where there is a reasonable probability of either of them being present. They are
structurally related and could both be formed in the same chemical process under
certain circumstances. However, no previous studies have reported simultaneous
trace level quantification of these two compounds. Herein, a chemical
derivatization scheme using benzaldehyde followed by LC-MS analysis is presented
to address that need. During method development, unexpectedly high recoveries
were encountered and presented a major challenge. A systematic investigation was
undertaken to understand the benzaldehyde derivatization reaction and determine
the underlying causes of the unacceptable recovery. It was found that this was
due to the presence of the counter ion of the API in the sample matrix. Employing
a 'matrix matching' sample preparation strategy, which involved acidifying the
derivatization reaction medium with benzoic acid, gave similar reaction rates for
the chemical derivatization in the presence and absence of the API salt and
accordingly more consistent recoveries. Resultantly, a robust method for
simultaneous quantification of hydrazine and acetohydrazide (1-100ppm) was
successfully developed and validated.
PMID- 27495372
TI - Expression of switch-associated protein 70 is associated with lymphocyte
activation and reduced disability in multiple sclerosis.
PMID- 27495373
TI - Development and Pilot Testing of Caregiver-Reported Pediatric Quality Measures
for Transitions Between Sites of Care.
AB - BACKGROUND: Few measures exist to assess pediatric transition quality between
care settings. The study objective was to develop and pilot test caregiver
reported quality measures for pediatric hospital and emergency department (ED) to
home transitions. METHODS: On the basis of an evidence review, we developed draft
caregiver-reported quality measures for transitions between sites of care. Using
the RAND-UCLA Modified Delphi method, a multistakeholder panel endorsed measures
for further development. Measures were operationalized into 2 surveys, which were
administered to caregivers of patients (n = 2839) discharged from Seattle
Children's Hospital between July 1 and September 1, 2014. Caregivers were
randomized to mail or telephone survey mode. Measure scores were computed as a
percentage of eligible caregivers who endorsed receiving the indicated care.
Differences in scores were examined according to survey mode and caregiver
characteristics. RESULTS: The Delphi panel endorsed 6 of 8 hospital to home
transition measures and 2 of 3 ED to home transitions measures. Scores differed
significantly according to mode for 1 measure. Caregivers with lower levels of
educational attainment and/or Spanish-speaking caregivers reported significantly
higher scores on 3 of the measures. The largest difference was reported for the
measure that assessed whether caregivers received assistance with scheduling
follow-up appointments; 92% score for caregivers with lower educational
attainment versus 79% for caregivers with higher educational attainment (P <
.001). CONCLUSIONS: We developed 8 new, evidence-based quality measures to assess
transition quality from the perspective of caregivers. Pilot testing of these
measures in a single institution yielded valuable insights for future testing and
implementation of these measures.
PMID- 27495375
TI - Deciphering the protein translation inhibition and coping mechanism of
trichothecene toxin in resistant fungi.
AB - In modern times for combating the deleterious soil microbes for improved
sustainable agricultural practices, there is a need to have a proper
understanding of the plant-microbe interactions present in the rhizospheric
microbiome of the plant roots. In the present study, the interactions of
trichodermin with petidyltransferase centre of ribosomal complex was studied by
molecular dynamics and in silico interaction methods to demonstrate its mechanism
of action and to decipher the possible reason how it may inhibit protein
synthesis at the ribosomal complex. Further we have illustrated how trichodermin
resistance protein (60S ribosomal protein L3) helps to overcome the deleterious
effects of trichothecene compounds like trichodermin. Normal mode analysis of
trichodermin resistance protein and 25S rRNA that constitutes the
petidyltransferase centre showed that the W-finger region of the protein moved
towards 25S rRNA. Further analysis of molecular dynamics simulation time frames
showed that several intermediate states of large motions of the protein molecules
towards the 25S rRNA which finally blocks the binding pocket of the trichodermin.
It indicated that this protein not only changes the local environment and
conformation of the petidyltransferase centre but also restrain trichodermin from
binding to the 25S rRNA at the petidyltransferase centre.
PMID- 27495374
TI - CUB domain-containing protein 1 and the epidermal growth factor receptor
cooperate to induce cell detachment.
AB - BACKGROUND: While localized malignancies often respond to available therapies,
most disseminated cancers are refractory. Novel approaches, therefore, are needed
for the treatment of metastatic disease. CUB domain-containing protein1 (CDCP1)
plays an important role in metastasis and drug resistance; the mechanism however,
is poorly understood. METHODS: Breast cancer cell lines were engineered to stably
express EGFR, CDCP1 or phosphorylation site mutants of CDCP1. These cell lines
were used for immunoblot analysis or affinity purification followed by immunoblot
analysis to assess protein phosphorylation and/or protein complex formation with
CDCP1. Kinase activity was evaluated using phosphorylation site-specific
antibodies and immunoblot analysis in in vitro kinase assays. Protein band
excision and mass spectrometry was utilized to further identify proteins
complexed with CDCP1 or DeltaCDCP1, which is a mimetic of the cleaved form of
CDCP1. Cell detachment was assessed using cell counting. RESULTS: This paper
reports that CDCP1 forms ternary protein complexes with Src and EGFR,
facilitating Src activation and Src-dependent EGFR transactivation. Importantly,
we have discovered that a class of compounds termed Disulfide bond Disrupting
Agents (DDAs) blocks CDCP1/EGFR/Src ternary complex formation and downstream
signaling. CDCP1 and EGFR cooperate to induce detachment of breast cancer cells
from the substratum and to disrupt adherens junctions. Analysis of CDCP1
containing complexes using proteomics techniques reveals that CDCP1 associates
with several proteins involved in cell adhesion, including adherens junction and
desmosomal cadherins, and cytoskeletal elements. CONCLUSIONS: Together, these
results suggest that CDCP1 may facilitate loss of adhesion by promoting
activation of EGFR and Src at sites of cell-cell and cell-substratum contact.
PMID- 27495376
TI - Proteomic analysis of 4-hydroxynonenal and nitrotyrosine modified proteins in RTT
fibroblasts.
AB - Rett syndrome (RTT) is a pervasive developmental disorder, primarily affecting
girls with a prevalence of 1 in every 10,000 births. A clear etiological factor
present in more than 90% of classical RTT cases is the mutation of the gene
encoding methyl-CpG-binding protein 2 (MECP2). Recent work from our group was
able to shown a systemic oxidative stress (OxS) in these patients that correlates
with the gravity of the clinical features. Using freshly isolated skin
fibroblasts from RTT patients and healthy subjects, we have performed a two
dimensional gel electrophoresis in order to evidence the oxidative modifications
of proteins with special focus on the formation of protein adducts with 4
hydroxynonenal (4-HNE PAs)-a major secondary product of lipid peroxidation- and
Nitrotyrosine, a marker derived from the biochemical interaction of nitric oxide
(NO) or nitric oxide-derived secondary products with reactive oxygen species
(ROS). Then, oxidatively modified spots were identified by mass spectrometry, LC
ESI-CID-MS/MS. Our results showed that 15 protein spots presented 4-HNE PAs
and/or nitrotyrosine adducts in fibroblasts proteome from RTT patients compared
to healthy control cells. Post-translationally modified proteins were related to
several functional categories, in particular to cytoskeleton structure and
protein folding. In addition, clear upregulated expression of the inducible NO
synthase (iNOS) with high nitrite levels were observed in RTT fibroblasts,
justifying the increased nitrotyrosine protein modifications. The present work
describes not only the proteomic profile in RTT fibroblasts, but also identifies
the modified proteins by 4-HNE and nitrotyrosine. Of note, for the first time, it
appears that a dysregulation of NO pathway can be associated to RTT
pathophysiology. In conclusion, the evidence of a wide range of proteins able to
forms adducts with 4-HNE, Nitrotyrosine or with both confirms the possible
alteration of several aspects of cellular functions that well correlates to the
complex clinical features of RTT patients.
PMID- 27495377
TI - Prevalence and predictors of drinking, binge drinking, and related health and
social problems in Puerto Rico.
AB - BACKGROUND: This paper examines prevalence and predictors of drinking, binge
drinking, and alcohol-related social and health problems in Puerto Rico. METHODS:
Respondents constitute a multi-stage household probability sample (N = 1,510)
from San Juan, Puerto Rico. The response rate was 83%. RESULTS: Men compared to
women (Coeff: .34; 95 CI = .19-.50; p < .001), those with more liberal norms
(Coeff: 1.05; 95 CI = .87-1.23; p < .001) and those with more positive attitudes
about drinking (Coeff: 1.06; 95 CI= .63-1.49; p < .001) have a higher average
number of weekly drinks. Those in the 40-49 age group have a lower mean number of
weekly drinks than those in the 18-29 age group (Coeff.: -.23; 95 CI = -.42-.03;
p < .02). Those with income between $30,001 and $40,000 a year compared to those
with less than $10,000, (OR: .28; 95 CI = .08-1.93; p < .039) report fewer
social/health problems. Protestants compared to Catholics (AOR: 1.94; 95 CI =
1.08-3.47; p < .026), those with more liberal drinking norms (AOR: 3.62; 95 CI =
1.87-6.99; p < .001) and more positive attitudes about drinking (AOR: 3.41; 95 CI
= 1.04-11.09; p < .001), and those who consume a higher number of drink per week
(AOR: 1.03; 95 CI = 1.01-1.05; p < .001) and binge (AOR: 3.52; 95 CI = 2.14-5.80;
p < .001) are more likely to report social and health problems associated with
alcohol use. DISCUSSION AND CONCLUSIONS: The finding that male gender is not
associated with binge drinking and social and health problems was not expected.
Puerto Ricans appear to drink less than the general population and Hispanics and
Puerto Ricans on the U.S. mainland. SCIENTIFIC SIGNIFICANCE: Up to date
epidemiological findings provide information about high risk groups and
correlates of alcohol problems in the population. These are now available for
Puerto Rico and can be used in the design of prevention interventions. (Am J
Addict 2016;25:478-485).
PMID- 27495378
TI - Vocal sac development and accelerated sexual maturity in the lesser swimming
frog, Pseudis minuta (Anura, Hylidae).
AB - Sexual maturity involves the differentiation of the reproductive system, the
maturation of germ cells, and the development of secondary sexual
characteristics. Even though this topic has received much attention, little is
known about the sequence of events that encompass reproductive maturation in
anurans and what it could reveal about the developmental basis of life cycle
evolution. The discovery of froglets of Pseudis minuta with incipient vocal sacs
calling in breeding pools alongside several larger adult specimens with fully
developed vocal sacs raised the question of the timing of sexual maturity in this
species. Here we describe the sequence and timing of differentiation, development
and maturation of the vocal sac apparatus and the testes in P. minuta (Anura,
Hylidae), in order to establish a timeline of events leading to sexual maturity.
Differentiation of the vocal sac apparatus begins at the final metamorphic
stages, earlier than reported for other species, and the vocal sac acquires its
final shape during the early postmetamorphic period. These modifications occur
after gonadal differentiation, which begins early during the larval period and
proceeds with a highly accelerated rate of development (e.g., secondary
spermatids appear well before metamorphic climax), a situation reported
previously for other anuran species only in the genus Pseudis. These results,
together with a skeletochronological analysis showing that some calling specimens
presented no lines of arrested growth, indicate acceleration in the timing of
sexual maturity in Pseudis, and raise questions about the
interdependence/decoupling during the development of the different components
involved in reaching the adult stage.
PMID- 27495379
TI - An approximate stationary solution for multi-allele neutral diffusion with low
mutation rates.
AB - We address the problem of determining the stationary distribution of the multi
allelic, neutral-evolution Wright-Fisher model in the diffusion limit. A full
solution to this problem for an arbitrary K*K mutation rate matrix involves
solving for the stationary solution of a forward Kolmogorov equation over a (K-1)
dimensional simplex, and remains intractable. In most practical situations
mutations rates are slow on the scale of the diffusion limit and the solution is
heavily concentrated on the corners and edges of the simplex. In this paper we
present a practical approximate solution for slow mutation rates in the form of a
set of line densities along the edges of the simplex. The method of solution
relies on parameterising the general non-reversible rate matrix as the sum of a
reversible part and a set of (K-1)(K-2)/2 independent terms corresponding to
fluxes of probability along closed paths around faces of the simplex. The
solution is potentially a first step in estimating non-reversible evolutionary
rate matrices from observed allele frequency spectra.
PMID- 27495380
TI - Coronary CTA and percutaneous coronary intervention - A symbiosis waiting to
happen.
PMID- 27495381
TI - Recognizing and managing common foot injuries.
AB - Subtle signs of foot and ankle fractures are often overlooked on initial
radiographs. This article describes several commonly missed foot and ankle
injuries and provides help in reviewing radiographs and identifying foot and
ankle fractures.
PMID- 27495382
TI - Serratia marcescens outbreak due to contaminated 2% aqueous chlorhexidine.
AB - INTRODUCTION AND OBJECTIVE: An outbreak of Serratia marcescens infections
outbreak is described, as well as the epidemiological study that linked the
outbreak to the use of 2% aqueous chlorhexidine antiseptic. METHOD: In late
November 2014 an increasing incidence of S. marcescens isolates was detected in
patients treated in the emergency department. It was considered a possible
outbreak, and an epidemiological investigation was started. RESULT: S. marcescens
was isolated in 23 samples from 16 patients and in all new bottles of two lots of
2% aqueous chlorhexidine. The contaminated disinfectant was withdrawn, and the
Spanish Drugs Agency was alerted (COS 2/2014). The epidemiological study showed
that strains isolated from clinical samples and from chlorhexidine belonged to
the same clone. No further isolates were obtained once the disinfectant was
withdrawn. CONCLUSION: The suspicion of an outbreak and the epidemiological study
were essential to control the incidence.
PMID- 27495383
TI - Gray matter segmentation of the spinal cord with active contours in MR images.
AB - OBJECTIVE: Fully or partially automated spinal cord gray matter segmentation
techniques for spinal cord gray matter segmentation will allow for pivotal spinal
cord gray matter measurements in the study of various neurological disorders. The
objective of this work was multi-fold: (1) to develop a gray matter segmentation
technique that uses registration methods with an existing delineation of the cord
edge along with Morphological Geodesic Active Contour (MGAC) models; (2) to
assess the accuracy and reproducibility of the newly developed technique on 2D
PSIR T1 weighted images; (3) to test how the algorithm performs on different
resolutions and other contrasts; (4) to demonstrate how the algorithm can be
extended to 3D scans; and (5) to show the clinical potential for multiple
sclerosis patients. METHODS: The MGAC algorithm was developed using a publicly
available implementation of a morphological geodesic active contour model and the
spinal cord segmentation tool of the software Jim (Xinapse Systems) for initial
estimate of the cord boundary. The MGAC algorithm was demonstrated on 2D PSIR
images of the C2/C3 level with two different resolutions, 2D T2* weighted images
of the C2/C3 level, and a 3D PSIR image. These images were acquired from 45
healthy controls and 58 multiple sclerosis patients selected for the absence of
evident lesions at the C2/C3 level. Accuracy was assessed though visual
assessment, Hausdorff distances, and Dice similarity coefficients.
Reproducibility was assessed through interclass correlation coefficients.
Validity was assessed through comparison of segmented gray matter areas in images
with different resolution for both manual and MGAC segmentations. RESULTS:
Between MGAC and manual segmentations in healthy controls, the mean Dice
similarity coefficient was 0.88 (0.82-0.93) and the mean Hausdorff distance was
0.61 (0.46-0.76) mm. The interclass correlation coefficient from test and retest
scans of healthy controls was 0.88. The percent change between the manual
segmentations from high and low-resolution images was 25%, while the percent
change between the MGAC segmentations from high and low resolution images was
13%. Between MGAC and manual segmentations in MS patients, the average Dice
similarity coefficient was 0.86 (0.8-0.92) and the average Hausdorff distance was
0.83 (0.29-1.37) mm. CONCLUSION: We demonstrate that an automatic segmentation
technique, based on a morphometric geodesic active contours algorithm, can
provide accurate and precise spinal cord gray matter segmentations on 2D PSIR
images. We have also shown how this automated technique can potentially be
extended to other imaging protocols.
PMID- 27495384
TI - Contrast-Enhanced Ultrasound in the Assessment of Patients with Indeterminate
Abdominal Findings at Positron Emission Tomography Imaging.
AB - Widespread use of fluorodeoxyglucose-positron emission tomography (PET) in cancer
imaging may result in a number of indeterminate and false-positive findings. We
investigated the role of contrast-enhanced ultrasound (CEUS) as a second-level
option after inconclusive PET. We reviewed CEUS images acquired over 4 y,
selecting the examinations performed specifically to better assess an unclear PET
image. Final diagnosis was confirmed by biopsy, surgery, further imaging or
follow-up. Seventy CEUS examinations were performed after a PET scan (44 PET
examinations, 19 PET-computer tomography [CT] examinations and 7 PET-CECT
examinations). The target organ was the liver in 54 cases, spleen in 12,
gallbladder in 2 and pancreas and kidney in one each. In 6 of 70 cases, CEUS was
performed because of a negative PET (no uptake) despite an abnormal finding on
the CT images of the PET-CT study; CEUS allowed a correct diagnosis in all of
these. In 20 of 70 cases, the PET findings were categorized as indeterminate and
non-specific (non-specific fluorodeoxyglucose uptake in PET report with no
standardized uptake value given); CEUS reached a correct diagnosis in 19 of the
20 cases with one false negative. In 34 of 70 cases, PET was indeterminate, but
specific (fluorodeoxyglucose uptake with a standardized uptake value provided);
CEUS reached a correct diagnosis in 30 of these 34 cases. In 10 of 70 cases, PET
was categorized as determinate but to be investigated because of discrepancy with
clinical or imaging findings; CEUS a definitive diagnosis in 9 of 10 cases. CEUS
proved to be effective option in the assessment of cancer patients with
indeterminate PET findings.
PMID- 27495386
TI - [EuroSCORE underestimate the mortality risk in cardiac valve surgery of Mexican
population].
AB - OBJECTIVE: The EuroSCORE (European System for cardiac operative risk evaluation)
stratifies cardiac risk surgery in easy and accessible manner; it was validated
in North America with good results but in many countries of Latin America is used
routinely without prior validation. Our objective was to validate the EuroSCORE
in patients with cardiac valve surgery at the Instituto Nacional de Cardiologia
Ignacio Chavez (INCICh) in Mexico. METHODS: EuroSCORE additive and logistic
models were used to predict mortality in adults undergoing cardiac valve surgery
from march 2004 to march 2008. The goodness of fit test of Hosmer-Lemeshow was
used to evaluate the calibration. The area under the ROC curve was calculated to
determinate discrimination. RESULTS: We included 1188 patients with ages of
51.3+/-14.5 years, 52% women. There were significant differences in the
prevalence of risk factors among the INCICh and the EuroSCORE populations. Total
mortality was 9.68% versus 5% and 5.6% predicted by additive and logistic
EuroSCORE. According to additive EuroSCORE the risk was low in 11.3%,
intermediate in 52.9% and high in 35.9%; for these groups the mortality was .7%,
6.34% and 17.4% against those predicted of 2%, 3.9% and 7.64%. Hosmer-Lemeshow
test had a P<.001 for both models and the area under the ROC curve was .707 and
.694 for additive and logistic EuroSCORE. CONCLUSION: In the INCICh 88.7% of
patients with cardiac valve surgery had intermediate to high risk and EuroSCORE
underestimated the risk of mortality.
PMID- 27495385
TI - Prognostic Significance of FDG Uptake of Bone Marrow on PET/CT in Patients With
Non-Small-Cell Lung Cancer After Curative Surgical Resection.
AB - BACKGROUND: This study evaluated the relationship between 18F-fluorodeoxyglucose
(FDG) uptake in bone marrow (BM) on positron emission tomography (PET)/computed
tomography (CT) imaging and serum inflammatory markers and assessed the
prognostic value of FDG uptake of BM in patients with non-small-cell lung cancer
(NSCLC) who underwent curative surgical resection. PATIENTS AND METHODS: We
retrospectively enrolled 110 NSCLC patients who underwent FDG PET/CT imaging and
subsequent curative surgical resection. The maximum standardized uptake value of
NSCLC (Tmax), mean FDG uptake of BM (BM SUV), and BM to liver uptake ratio (BLR)
were measured. The relationships between BM SUV, BLR, and serum inflammatory
markers were evaluated and the prognostic significance of PET/CT parameters for
predicting recurrence-free survival (RFS) and overall survival (OS) were
assessed. RESULTS: BM SUV and BLR were significantly associated with serum C
reactive protein (CRP) level, white blood cell count, and the neutrophil to
lymphocyte ratio (NLR). BLR was also significantly correlated with serum albumin
and the platelet to lymphocyte ratio. In univariate analysis, tumor, node,
metastases (TNM) stage, serum CRP level, NLR, Tmax, and BLR were significant
prognostic factors for RFS and OS, whereas histopathology and tumor size were
significant prognostic factors for RFS. In multivariate analysis, BLR,
histopathology, TNM stage, and Tmax were independent prognostic factors for RFS
and TNM stage and Tmax were independent prognostic factors for OS. CONCLUSION:
FDG uptake of BM on PET/CT imaging was correlated with serum inflammatory markers
and was an independent predictor for RFS, along with FDG uptake of NSCLC.
PMID- 27495387
TI - Triumph and adversity: Exploring the complexities of consumer storytelling in
mental health nursing education.
AB - Consumer participation in the education of health professionals is increasing,
particularly in mental health nursing education and storytelling remains the most
frequent approach to consumer involvement. The use of story has tended to be
accepted as a legitimate educational tool with limited critique or consideration
of its potential consequences presented within the academic literature. A
qualitative exploratory research study was undertaken with mental health nurse
academics (n = 34) and consumer educators and academics (n = 12), to investigate
the perceptions and experiences of mental health nurses and consumers regarding
the involvement of consumers in mental health nursing education. Data were
analysed thematically. Story was a major theme to emerge from consumer
participants and received some attention from nurse academics. Consumers and
nurses both referred to the power of story to convey the human experience of
mental illness diagnosis and service use; and the vulnerability that can result
from storytelling. Consumers also described: story as expectation; preparation
and support; and the politics of story. All participants supported the value of
storytelling in mental health nursing education. Consumers had considered the
complexities in far greater detail. The ongoing value of story as an educational
technique requires further research. Equally important is considering a broader
range of educational roles for mental health consumers.
PMID- 27495388
TI - A comprehensive evaluation of the [2-14C](-)-epicatechin metabolome in rats.
AB - Following ingestion of [2-14C](-)-epicatechin by rats, radioactivity in urine,
feces, body fluids and tissues collected over a 72h period, was measured and 14C
metabolites were analyzed by HPLC-MS2 with a radioactivity monitor. In total 78%
of the ingested radioactivity was absorbed from the gastrointestinal tract (GIT),
and then rapidly eliminated from the circulatory system via renal excretion. A
peak plasma concentration occurred 1h after intake corresponding to ~0.7% of
intake. Low amounts of radioactivity, <2% of intake, appeared transiently in body
tissues. Glucuronidation and methylation of (-)-epicatechin began in the duodenum
but occurred more extensively in the jejunum/ileum. Radioactivity reaching the
cecum after 6-12h was predominantly in the form of the ring fission metabolites 5
(3',4'-dihydroxyphenyl)-gamma-valerolactone and 5-(3',4'-dihydroxyphenyl)-gamma
hydroxyvaleric acid along with smaller amounts of their phase II metabolites. Low
levels of metabolites were detected in the colon. Of the ingested radioactivity,
19% was voided in feces principally as ring-fission metabolites. The main
components in plasma were (-)-epicatechin-5-O-glucuronide and 3'-O-methyl-(-)
epicatechin-5-O-glucuronide with small amounts of (-)-epicatechin, 3'-O-methyl-(
)-epicatechin, 5-(3'-hydroxyphenyl)-gamma-hydroxyvaleric acid-4'-glucuronide and
hippuric acid also being detected. No oxidized products of (-)-epicatechin were
detected. No compelling evidence was obtained for biliary recycling of
metabolites. The findings demonstrate substantial differences in the metabolism
of (-)-epicatechin by rats and humans. Caution should, therefore, be exercised
when using animal models to draw conclusions about effects induced by (-)
epicatechin intake in humans.
PMID- 27495389
TI - Hsp90 directly interacts, in vitro, with amyloid structures and modulates their
assembly and disassembly.
AB - BACKGROUND: The 90kDa heat shock protein (Hsp90) participates in regulating the
homeostasis of cellular proteins and was considered one of the key chaperones
involved in the control and regulation of amyloid deposits. Hsp90 interacts with
the amyloid protein tau through tau aggregation-prone regions, including the
VQIVYK hexapeptide motif. This hexapeptide, which self-aggregates, forming
amyloid fibrils, is widely used to model amyloid formation mechanisms. Despite
evidence showing that Hsp90 interacts directly with Ac-VQIVYK-NH2, its role in
the hexapeptide fibrillation process and its binding to peptide structures have
not yet been determined. METHODS: Various biochemical and biophysical techniques,
including ultracentrifugation, spectrophotometry, spectrofluorimetry, and
electron microscopy, were employed to assess the effects of Hsp90 on Ac-VQIVYK
NH2 assembly and disassembly processes. RESULTS: At sub-stoichiometric
concentrations, Hsp90 bound directly to Ac-VQIVYK-NH2 amyloid structures in
vitro, with each Hsp90 dimer interacting with an amyloid structure made of around
50 hexapeptide subunits. Hsp90 inhibited Ac-VQIVYK-NH2 assembly by increasing the
critical concentrations of Ac-VQIVYK-NH2 required for assembly. Hsp90 also
inhibited the disassembly of Ac-VQIVYK-NH2 amyloid fibrils and promoted their
rescue. CONCLUSIONS: A model explaining the dual effect of Hsp90 on the Ac-VQIVYK
NH2 amyloid fibrillation process has been proposed. GENERAL SIGNIFICANCE: These
in vitro results provide new insights into the possible roles of molecular
chaperones in modulating amyloid structures by limiting the spread of toxic
species.
PMID- 27495390
TI - Methods for the physical characterization and quantification of extracellular
vesicles in biological samples.
AB - BACKGROUND: Our body fluids contain a multitude of cell-derived vesicles,
secreted by most cell types, commonly referred to as extracellular vesicles. They
have attracted considerable attention for their function as intercellular
communication vehicles in a broad range of physiological processes and
pathological conditions. Extracellular vesicles and especially the smallest type,
exosomes, have also generated a lot of excitement in view of their potential as
disease biomarkers or as carriers for drug delivery. In this context, state-of
the-art techniques capable of comprehensively characterizing vesicles in
biological fluids are urgently needed. SCOPE OF REVIEW: This review presents the
arsenal of techniques available for quantification and characterization of
physical properties of extracellular vesicles, summarizes their working
principles, discusses their advantages and limitations and further illustrates
their implementation in extracellular vesicle research. MAJOR CONCLUSIONS: The
small size and physicochemical heterogeneity of extracellular vesicles make their
physical characterization and quantification an extremely challenging task.
Currently, structure, size, buoyant density, optical properties and zeta
potential have most commonly been studied. The concentration of vesicles in
suspension can be expressed in terms of biomolecular or particle content
depending on the method at hand. In addition, common quantification methods may
either provide a direct quantitative measurement of vesicle concentration or
solely allow for relative comparison between samples. GENERAL SIGNIFICANCE: The
combination of complementary methods capable of detecting, characterizing and
quantifying extracellular vesicles at a single particle level promises to provide
new exciting insights into their modes of action and to reveal the existence of
vesicle subpopulations fulfilling key biological tasks.
PMID- 27495391
TI - GRIND2-based 3D-QSAR and prediction of activity spectra for symmetrical bis
pyridinium salts with promastigote antileishmanial activity.
AB - Leishmaniasis is a major group of neglected tropical diseases caused by the
protozoan parasite Leishmania. About 12 million people are affected in 98
countries and 350 million people worldwide are at risk of infection. Current
leishmaniasis treatments rely on a relatively small arsenal of drugs, including
amphotericin B, pentamidine and others, which in general have some type of
inconvenience. Recently, we have synthesized antileishmanial bis-pyridinium
derivatives and symmetrical bis-pyridinium cyclophanes. These compounds are
considered structural analogues of pentamidine, where the amidino moiety,
protonated at physiological pH, is replaced by a positively charged nitrogen atom
as a pyridinium ring. In this work, a statistically significant GRIND2-based 3D
QSAR model was built and biological activity predictions were in silico carried
out allowing rationalization of the different activities recently obtained
against Leishmania donovani (in L. donovani promastigotes) for a data set of 19
bis-pyridinium compounds. We will emphasize the most important structural
requirements to improve the biological activity and probable interactions with
the biological receptor as a guide for lead and prototype optimization. In
addition, since no information about the actual biological target for this series
of active compounds is provided, we have used Prediction of Activity Spectra for
Biologically Active Substances to propose our compounds as potential nicotinic
alpha6beta3beta4alpha5 receptor antagonists. This proposal is reinforced by the
high structural similarity observed between our compounds and several
anthelmintic drugs in current clinical use, which have the same drug action
mechanism here predicted. Such new findings would be confirmed with further and
additional experimental assays.
PMID- 27495734
TI - Effect of a cheese rich in angiotensin-converting enzyme-inhibiting peptides
(Gamalost((r))) and a Gouda-type cheese on blood pressure: results of a
randomised trial.
AB - BACKGROUND: High blood pressure (BP) is the leading risk factor for global
disease burden, contributing to 7% of global disability adjusted life years.
Angiotensin converting enzyme (ACE)-inhibiting bioactive peptides have the
potential to reduce BP in humans. These peptides have been identified in many
dairy products and have been associated with significant reductions in BP.
OBJECTIVE: The objective of this trial was to examine whether a cheese rich in
ACE-inhibiting peptides (Gamalost((r))), or a standard Gouda-type cheese could
lower BP. DESIGN: A total of 153 healthy participants were randomised to one of
three parallel arms: Gamalost((r)) (n=53, 50 g/day for 8 weeks), Gouda-type
cheese (n=50, 80 g/day for 8 weeks), and control (n=50). BP and anthropometric
measurements were taken at the baseline and at the end, with an additional BP
measurement midway. Based on BP at baseline, participants were categorised as
having optimal BP (<120/<80 mmHg), normal-high BP (120-139/80-89 mmHg), or being
hypertensive (>140/>90 mmHg). Questionnaires about lifestyle, health, and dietary
habits were completed at baseline, midway and end. RESULTS: In total, 148
participants (mean age 43, 52% female) completed the intervention. There were no
differences among the three groups in relevant baseline characteristics. BP was
reduced in the entire study population, but the cheese groups did not differ from
control. However, in a subgroup of participants with slightly elevated BP, BP at
4 weeks of intervention seemed to be borderline significantly more reduced in the
Gamalost((r)) group compared with the control group (Dunnett test: diastolic BP
3.5 mmHg, 95% confidence interval (CI) -7.3, 0.4, systolic BP: -4.3 mmHg, 95% CI
9.8, 1.1). CONCLUSION: An intention-to-treat analysis of the data showed no
cheese effect upon BP compared to control, but Gamalost((r)) seemed to have a
small, non-significant lowering effect on diastolic BP after 4 weeks in people
with a normal-high BP.
PMID- 27495735
TI - Influence of different anaesthetic protocols over the sperm quality on the fresh,
chilled (4 degrees C) and frozen-thawed epididymal sperm samples in domestic
dogs.
AB - This study assessed the influence of three different anaesthetic protocols on
semen quality obtained from the epididymis. Sixty male dogs undergoing to routine
sterilization were assigned to three anaesthetic protocols: thiopental group (TG,
n = 20), propofol group (PG, n = 20) and ketamine-dexmedetomidine group (KDG, n =
20). Immediately after orchidectomy, the cauda epididymides and vas deferent
ducts were isolated and then a retrograde flushing was performed to collect
spermatozoa. In experiment 1, after the initial evaluation of the semen (sperm
concentration, sperm motility and the percentages of live spermatozoa, abnormal
spermatozoa and acrosome membrane integrity), semen samples were diluted in Tris
glucose-egg yolk extender and chilled for 48 hr, and the sperm motility was
assessed at 6, 24 and 48 hr. In experiment 2, semen samples were diluted in Tris
glucose-egg yolk extender and chilled for 24 hr, and then samples were frozen in
two extenders with different glycerol concentrations, to reach a final
concentration of 50-100 * 10(6) spermatozoa ml(-1) , 20% egg yolk, 0.5% Equex and
4% and 5% glycerol, respectively. Mean values of total sperm concentration, sperm
viability and the percentages of intact acrosome and abnormal spermatozoa were
not significantly different between experimental groups, and therefore, the
anaesthetic protocols assessed did not affect sperm parameters mentioned above.
However, our study confirmed a detrimental effect of the use of thiopental (TG)
over the total sperm motility (p < 0.05) and progressive sperm motility (p <
0.05) of the fresh and chilled epididymal sperm samples. The anaesthetic
protocols including the application of propofol or ketamine-dexmedetomidine can
be used to recover sperm in domestic canids without significant changes in sperm
quality compared when semen is collected routinely and these techniques could be
applicable to endangered wild canids.
PMID- 27495736
TI - Inconsistent results in the analysis of ALK rearrangements in non-small cell lung
cancer.
AB - BACKGROUND: Identification of targetable EML4-ALK fusion proteins has
revolutionized the treatment of a minor subgroup of non-small cell lung cancer
(NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded
as the gold standard for detection of ALK rearrangements, ALK
immunohistochemistry (IHC) is often used as screening tool in clinical practice.
In order to unbiasedly analyze the diagnostic impact of such a screening
strategy, we compared ALK IHC with ALK FISH in three large representative Swedish
NSCLC cohorts incorporating clinical parameters and gene expression data.
METHODS: ALK rearrangements were detected using FISH on tissue microarrays
(TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein
expression was detected using IHC, applying the antibody clone D5F3 with two
different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC
protocol). Gene expression microarray data (Affymetrix) was available for 194
patients. RESULTS: ALK rearrangements were detected in 1.7 % in the complete
cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein
expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the
in house Dako protocol, respectively. The specificity and accuracy of IHC was
high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in
house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were
positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %)
tumors showed high ALK gene expression (>= 6 AU) and of them only three were
positive by either FISH or IHC. CONCLUSION: The overall frequency of ALK
rearrangements based on FISH was lower than previously reported. The sensitivity
of both IHC assays was low, and the concordance between the FISH and the IHC
assays poor, questioning current strategies to screen with IHC prior to FISH or
completely replace FISH by IHC.
PMID- 27495738
TI - I86A/C295A mutant secondary alcohol dehydrogenase from Thermoanaerobacter
ethanolicus has broadened substrate specificity for aryl ketones.
AB - Thermoanaerobacter ethanolicus secondary alcohol dehydrogenase (SADH) reduces
aliphatic ketones according to Prelog's Rule, with binding pockets for small and
large substituents. It was shown previously that the I86A mutant SADH reduces
acetophenone, which is not a substrate of wild-type SADH, to give the anti-Prelog
R-product (Musa, M. M.; Lott, N.; Laivenieks, M.; Watanabe, L.; Vieille, C.;
Phillips, R. S. ChemCatChem2009, 1, 89-93.). However, I86A SADH did not reduce
aryl ketones with substituents larger than fluorine. We have now expanded the
small pocket of the active site of I86A SADH by mutation of Cys-295 to alanine to
allow reaction of substituted acetophenones. As predicted, the double mutant
I86A/C295A SADH has broadened substrate specificity for meta-substituted, but not
para-substituted, acetophenones. However, the increase of the substrate
specificity of I86A/C295A SADH is accompanied by a decrease in the kcat/Km values
of acetophenones, possibly due to the substrates fitting loosely inside the more
open active site. Nevertheless, I86A/C295A SADH gives high conversions and very
high enantiomeric excess of the anti-Prelog R-alcohols from the tested
substrates.
PMID- 27495737
TI - Molecular cloning of glucose transporter 1 in grouper Epinephelus coioides and
effects of an acute hyperglycemia stress on its expression and glucose tolerance.
AB - The glucose transporter family proteins play pivotal roles in glucose metabolism.
In this study, we successfully cloned the orange spotted grouper (Epinephelus
coioides) glucose transporter 1 (EcGlut1) gene (GenBank accession: JQ623903). The
full-length EcGlut1 cDNA was 2126 bp with a 1476 bp ORF, a 437bp5'-UTR and
223bp3'-UTR. EcGlut1 is predicted to encode a 491 amino acid protein with a MW of
53.9 kDa, a pI of 8.66 and a Pfam domain. Bioinformatics analysis revealed that
EcGlut1 was evolutionally conserved between fishes with 80-89 % amino acid
identities. EcGlut1 was expressed predominantly in heart and liver and at lower
levels in muscle, intestine, stomach and brain. We also investigated the effect
of acute hyperglycemia stress on EcGlut1 expression. In glucose tolerance test,
changes in EcGlut1 mRNA expression in response to glucose injection and glucose
metabolism-related indictors were assessed at the same time. Glucose injection
significantly suppressed EcGlut1 mRNA expression in liver at 12 h and in brain at
24 h postinjection (P < 0.05). EcGlut1 mRNA levels in heart were increased at 6 h
(P < 0.05). Plasma glucose level increased significantly and reached its maximum
at 3 h postinjection (P < 0.05). The spatiotemporal expression of EcGlut1 and
glucose metabolism suggested that orange spotted grouper might rely on fat
anabolism to reduce acute hyperglycemia stress and the delayed transcription of
EcGlut1 gene might be one reason for glucose intolerance in E. coioides.
PMID- 27495739
TI - Processing of A-form ssDNA by cryptic RNase H fold exonuclease PF2046.
AB - RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease
that cleaves after the second nucleotide from the 3' end of ssDNA and prefers
poly-dT over poly-dA as a substrate. In our crystal structure of PF2046 complexed
with an oligonucleotide of four thymidine nucleotides (dT4), PF2046 accommodates
dT4 tightly in a groove and imposes steric hindrance on dT4 mainly by Phe220 such
that dT4 assumes the A-form. As poly-dA prefer B-form due to the stereochemical
restrictions, the A-form ssDNA binding by PF2046 should disfavor the processing
of poly-dA. Phe220 variants display reduced activity toward poly-dA and the A
form appears to be a prerequisite for the processing by PF2046.
PMID- 27495740
TI - Selenium and redox signaling.
AB - Selenium compounds that contain selenol functions or can be metabolized to
selenols are toxic via superoxide and H2O2 generation, when ingested at dosages
beyond requirement. At supra-nutritional dosages various forms of programmed cell
death are observed. At physiological intakes, selenium exerts its function as
constituent of selenoproteins, which overwhelmingly are oxidoreductases. Out of
those, the glutathione peroxidases counteract hydroperoxide-stimulated signaling
cascades comprising inflammation triggered by cytokines or lipid mediators,
insulin signaling and different forms of programmed cell death. Similar events
are exerted by peroxiredoxins, which functionally depend on the selenoproteins of
the thioredoxin reductase family. The thiol peroxidases of both families can,
however, also act as sensors for hydroperoxides, thereby initiating signaling
cascades. Although the interaction of selenoproteins with signaling events has
been established by genetic techniques, the in vivo relevance of these findings
is still hard to delineate for several reasons: The biosynthesis of individual
selenoproteins responds differently to variations of selenium intakes; selenium
is preferentially delivered to privileged tissues via inter-organ trafficking and
receptor-mediated uptake, and only half of the selenoproteins known by sequence
have been functionally characterized. The fragmentary insights do not allow any
uncritical use of selenium for optimizing human health.
PMID- 27495741
TI - A review of teaching ethics in the dental curriculum: challenges and future
developments.
AB - This study considers the role and status of the teaching of ethics on the dental
undergraduate curriculum. The study reviews current developments in the delivery
of dental ethics education and in particular focuses on the development of new
pedagogies and curricula content. The study then critically considers the
consequences of a squeezed curricula and the consequent reliance on professional
regulation as shorthand for the ethical development of students. The study
concludes that, although great strides have been made in improving the teaching
of ethics in dental education, further dialogue is needed to better include
patient views and develop a more theoretically robust approach to self
reflection.
PMID- 27495742
TI - The early events underlying genome evolution in a localized Sinorhizobium
meliloti population.
AB - BACKGROUND: Population genetic analyses based on genome-wide sequencing data have
been carried out for Sinorhizobium medicae and S. meliloti, two closely related
bacterial species forming nitrogen-fixing symbioses with plants of the genus
Medicago. However, genome coverage was low or the isolates had a broad geographic
distribution, making it difficult to interpret the estimated diversity and to
unravel the early events underlying population genetic variations and ecological
differentiation. RESULTS: Here, to gain insight into the early genome level
variation and diversification within S. meliloti populations, we first used
Illumina paired-end reads technology to sequence a new clone of S. meliloti
strain GR4, a highly competitive strain for alfalfa nodulation. The Illumina data
and the GR4 genome sequence previously obtained with 454 technology were used to
generate a high-quality reference genome sequence. We then used Illumina
technology to sequence the genomes of 13 S. meliloti isolates representative of
the genomic variation within the GR4-type population, obtained from a single
field site with a high degree of coverage. The genome sequences obtained were
analyzed to determine nucleotide diversity, divergence times, polymorphism and
genomic variation. Similar low levels of nucleotide diversity were observed for
the chromosome, pSymB and pSymA replicons. The isolates displayed other types of
variation, such as indels, recombination events, genomic island excision and the
transposition of mobile elements. CONCLUSIONS: Our results suggest that the GR4
type population has experienced a process of demographic expansion and behaves as
a stable genotypic cluster of genome-wide similarity, with most of the genome
following a clonal pattern of evolution. Although some of genetic variation
detected within the GR4-type population is probably due to genetic drift, others
might be important in diversification and environmental adaptation.
PMID- 27495743
TI - Short-term test-retest-reliability of conditioned pain modulation using the cold
heat-pain method in healthy subjects and its correlation to parameters of
standardized quantitative sensory testing.
AB - BACKGROUND: Conditioned Pain Modulation (CPM) is often used to assess human
descending pain inhibition. Nine different studies on the test-retest-reliability
of different CPM paradigms have been published, but none of them has investigated
the commonly used heat-cold-pain method. The results vary widely and therefore,
reliability measures cannot be extrapolated from one CPM paradigm to another. Aim
of the present study was to analyse the test-retest-reliability of the common
heat-cold-pain method and its correlation to pain thresholds. METHODS: We tested
the short-term test-retest-reliability within 40 +/- 19.9 h using a cold-water
immersion (10 degrees C, left hand) as conditioning stimulus (CS) and heat pain
(43-49 degrees C, pain intensity 60 +/- 5 on the 101-point numeric rating scale,
right forearm) as test stimulus (TS) in 25 healthy right-handed subjects
(12females, 31.6 +/- 14.1 years). The TS was applied 30s before (TSbefore),
during (TSduring) and after (TSafter) the 60s CS. The difference between the pain
ratings for TSbefore and TSduring represents the early CPM-effect, between
TSbefore and TSafter the late CPM-effect. Quantitative sensory testing (QST, DFNS
protocol) was performed on both sessions before the CPM assessment. STATISTICS:
paired t-tests, Intraclass correlation coefficient (ICC), standard error of
measurement (SEM), smallest real difference (SRD), Pearson's correlation, Bland
Altman analysis, significance level p < 0.05 with Bonferroni correction for
multiple comparisons, when necessary. RESULTS: Pain ratings during CPM correlated
significantly (ICC: 0.411...0.962) between both days, though ratings for TSafter
were lower on day 2 (p < 0.005). The early (day 1: 16.7 +/- 11.7; day 2: 19.5 +/-
11.9; ICC: 0.618, SRD: 20.2) and late (day 1: 1.7 +/- 9.2; day 2: 7.6 +/- 11.5;
ICC: 0.178, SRD: 27.0) CPM effect did not differ significantly between both days.
Both early and late CPM-effects did not correlate with the pain thresholds.
CONCLUSIONS: The short-term test-retest-reliability of the early CPM-effect using
the heat-cold-pain method in healthy subjects achieved satisfying results in
terms of the ICC. The SRD of the early CPM effect showed that an individual
change of > 20 NRS can be attributed to a real change rather than chance. The
late CPM-effect was weaker and not reliable.
PMID- 27495744
TI - TiO2 microspheres containing magnetic nanoparticles for intra-arterial
hyperthermia.
AB - Magnetic microspheres measuring 15-35 um in diameter are believed to be useful
for intra-arterial hyperthermia. In this study, we attempted to prepare titanium
dioxide (TiO2 ) microspheres containing magnetic nanoparticles (MNPs). MNP
containing TiO2 microspheres with diameters of approximately 30 um were
successfully obtained by sol-gel reaction of titanium tetraisopropoxide in a
water-in-oil emulsion with added cosurfactant of 1-butanol and subsequent heat
treatment at 200 degrees C. The microspheres showed ferrimagnetism owing to high
content of MNPs in approximately 60 wt % and had a low-crystalline TiO2 matrix.
Furthermore, the agar phantom was heated to above 43 degrees C after
approximately 1 min under an alternating magnetic field of 100 kHz and 300 Oe and
showed in vitro biocompatibility similar to that of MNP-free TiO2 microspheres.
(c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B:
2308-2314, 2017.
PMID- 27495745
TI - Clinical Application of Pluripotent Stem Cells: An Alternative Cell-Based Therapy
for Treating Liver Diseases?
AB - The worldwide shortage of donor livers for organ and hepatocyte transplantation
has prompted the search for alternative therapies for intractable liver diseases.
Cell-based therapy is envisaged as a useful therapeutic option to recover and
stabilize the lost metabolic function for acute liver failure, end-stage and
congenital liver diseases, or for those patients who are not considered eligible
for organ transplantation. In recent years, research to identify alternative and
reliable cell sources for transplantation that can be derived by reproducible
methods has been encouraged. Human pluripotent stem cells (PSCs), which comprise
both embryonic and induced PSCs, may offer many advantages as an alternative to
hepatocytes for liver cell therapy. Their capacity for expansion, hepatic
differentiation and self-renewal make them a promising source of unlimited
numbers of hepatocyte-like cells for treating and repairing damaged livers.
Immunogenicity and tumorigenicity of human PSCs remain the bottleneck for
successful clinical application. However, recent advances made to develop disease
corrected hepatocyte-like cells from patients' human-induced PSCs by gene editing
have opened up many potential gateways for the autologous treatment of hereditary
liver diseases, which may likely reduce the risk of rejection and the need for
lifelong immunosuppression. Well-defined methods to reduce the expression of
oncogenic genes in induced PSCs, including protocols for their complete and safe
hepatic differentiation, should be established to minimize the tumorigenicity of
transplanted cells. On top of this, such new strategies are currently being
rigorously tested and validated in preclinical studies before they can be safely
transferred to clinical practice with patients.
PMID- 27495747
TI - Recent Advances in Mammalian Target of Rapamycin Inhibitor Use in Heart and Lung
Transplantation.
AB - The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are
increasingly used in cardiothoracic transplantation. Several recent clinical
trials have demonstrated their efficacy in combination with reduced cyclosporine
dosing in de novo heart transplant recipients, in particular with everolimus. A
number of other studies have demonstrated their efficacy for improving renal
function and reducing calcineurin inhibitor use, attenuating cardiac allograft
vasculopathy progression and reducing cytomegalovirus infections in maintenance
heart transplant populations. A growing body of literature, including a small
number of clinical trials, now describes the use mTOR inhibitors in lung
transplant recipients. The benefits in this population include improved lung and
renal function in limited studies. Considerably less evidence is available in
pediatric heart transplantation, though similar indications in the maintenance
therapy population have been described. The benefits of mTOR inhibitors must be
weighed against the increased risk of adverse events and drug intolerance
compared with other primary immunosuppressants, and discontinuation rates are
particularly high in lung transplant recipients. The risks of surgical wound
healing complications in transplant recipients receiving mTOR inhibitors
previously or actively supported by mechanical circulatory support devices
remains poorly described in the current literature. The current role and recent
evidence for mTOR inhibitor use in heart and lung transplantation is examined in
this review.
PMID- 27495748
TI - Unraveling the Process of the Dying Heart: Do Not Leave Science Alone for the
Heart to Live Again.
PMID- 27495749
TI - Performance-Based Measures Associate With Frailty in Patients With End-Stage
Liver Disease.
AB - BACKGROUND: Physical frailty, as measured by the Fried Frailty Index, is
increasingly recognized as a critical determinant of outcomes in patients with
cirrhosis. However, its utility is limited by the inclusion of self-reported
components. We aimed to identify performance-based measures associated with
frailty in patients with cirrhosis. METHODS: Patients with cirrhosis, aged 50
years or older, underwent: 6-minute walk test (cardiopulmonary endurance), chair
stands in 30 seconds (muscle endurance), isometric knee extension (lower
extremity strength), unipedal stance time (static balance), and maximal step
length (dynamic balance/coordination). Linear regression associated each physical
performance test with frailty. Principal components exploratory factor analysis
evaluated the interrelatedness of frailty and the 5 physical performance tests.
RESULTS: Of 40 patients with cirrhosis, with a median age of 64 years and Model
for End-stage Liver Disease (MELD) MELD of 12.10 (25%) were frail by Fried
Frailty Index >=3. Frail patients with cirrhosis had poorer performance in 6
minute walk test distance (231 vs 338 m), 30-second chair stands (7 vs 10),
isometric knee extension (86 vs 122 Newton meters), and maximal step length (22
vs 27 in. (P <= 0.02 for each). Each physical performance test was significantly
associated with frailty (P < 0.01), even after adjustment for MELD or hepatic
encephalopathy. Principal component factor analysis demonstrated substantial, but
unique, clustering of each physical performance test to a single factor-frailty.
CONCLUSIONS: Frailty in cirrhosis is a multidimensional construct that is
distinct from liver dysfunction and incorporates endurance, strength, and
balance. Our data provide specific targets for prehabilitation interventions
aimed at reducing frailty in patients with cirrhosis in preparation for liver
transplantation.
PMID- 27495751
TI - Activated Renal Dendritic Cells Cross Present Intrarenal Antigens After Ischemia
Reperfusion Injury.
AB - BACKGROUND: The healthy kidney contains an extensive population of renal
mononuclear phagocytes (RMPs), with substantial phenotypic and functional
diversity. However, how this diverse population is affected by ischemia
reperfusion injury (IRI), an obligate part of renal transplantation, is not yet
well understood. The aim of this study was to characterize the phenotypic and
functional alterations in RMPs induced by IRI. METHODS: Renal mononuclear
phagocytes were studied 24 and 72 hours after 30 minutes of renal ischemia or
sham operation. Kidneys were digested and the phenotypes of renal leukocyte
populations were analyzed via flow cytometry. Multiphoton microscopy was used to
image renal dendritic cells (DCs) in vivo using CD11c reporter mice. The capacity
of renal DCs to present antigen was examined by assessment of proliferation of
ovalbumin-specific T cells in rat insulin promoter-membrane-bound ovalbumin
transgenic mice after sham or IRI procedures. RESULTS: Ischemia-reperfusion
injury induced influx of monocytes, DCs, macrophages, and neutrophils into the
kidney. Classification of RMP subpopulations based on CD11b/CD11c expression
demonstrated that the RMPs that increased in response to IRI were predominantly
newly recruited monocyte-derived inflammatory DCs. In vivo multiphoton imaging of
CD11c-EYFP mice revealed that intrarenal DCs exhibited increased number and
activity of dendrites in the postischemic period. Ischemia-reperfusion injury
also promoted DC-dependent cross-presentation of renal antigens to CD8 T cells in
the draining lymph node. CONCLUSIONS: In response to renal IRI, RMP populations
are skewed toward those derived from inflammatory monocyte precursors. In
addition, renal DCs undergo functional activation, increasing their capacity to
activate antigen-specific CD8 T cells in renal draining lymph nodes.
PMID- 27495753
TI - Fulminant Hepatic Failure as a Risk Factor for Cytomegalovirus Infection in
Children Receiving Preemptive Therapy After Living Donor Liver Transplantation.
AB - BACKGROUND: Cytomegalovirus (CMV) is one of the most common causes of infection
after solid organ transplantation with symptomatic disease occurring at an
incidence of 20% to 40% without preventative measures. Although CMV
donor+/recipient - serostatus is well known to be a risk factor, there is little
data about other risk factors for CMV infection in the setting of pediatric liver
transplantation (LT). We hypothesized that fulminant hepatic failure (FHF) may be
a risk factor for CMV infection given anecdotal reports of complications
associated with FHF. METHODS: We conducted medical chart review of children who
underwent LT at a tertiary children's hospital in Tokyo between November 2005 and
October 2015. We evaluated the risk factors, especially FHF, and prognosis for
CMV infection under preemptive therapy. RESULTS: Three hundred thirty-seven
living donor LT were analyzed. Underlying diseases were cholestatic liver disease
(n = 172, 51%), metabolic disease (n = 59, 18%), and FHF (n = 51, 15%). Among 337
LT, 147 (44%) recipients developed CMV antigenemia. In multivariate analysis, FHF
(odds ratio, 4.99; 95% confidence interval, 1.86-13.40; P = 0.001) and CMV
serostatus were independent risk factors for developing CMV antigenemia. Positive
donor serostatus was significantly associated with development of antigenemia
within 1-year post-LT regardless of recipient serostatus (P <0.001). On the other
hand, positive recipient status was associated with CMV antigenemia in the first
21 days (P <0.001). Only 12 (3.6%) of 337 children developed CMV disease.
CONCLUSIONS: Fulminant hepatic failure was found to be a risk factor for CMV
infection independent of CMV serostatus.
PMID- 27495752
TI - Increased Extravascular Lung Water and Plasma Biomarkers of Acute Lung Injury
Precede Oxygenation Impairment in Primary Graft Dysfunction After Lung
Transplantation.
AB - BACKGROUND: After lung transplantation (LT), early prediction of grade 3
pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We
hypothesized that it could be improved using extravascular lung water (EVLWi) and
plasma biomarkers of acute lung injury. METHODS: After institutional review board
approval and informed consent, consecutive LT recipients were included.
Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial
(soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial
biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length
and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24,
48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined
according to the International Society for Lung and Heart Transplantation
definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction
of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors,
EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm,
using logistic model and areas under the receiver operating characteristic curves
(AUCs). RESULTS: In 47 LT recipients, 10 developed grade 3 PGD, which was obvious
at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule
1 and endocan (both forms) were not associated with grade 3 PGD. Significant
predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC,
0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal
cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760
pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. CONCLUSIONS: Immediate
postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios
were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early
therapeutic interventions.
PMID- 27495755
TI - The Optimal Timing of Hepatitis C Therapy in Transplant Eligible Patients With
Child B and C Cirrhosis: A Cost-Effectiveness Analysis.
AB - BACKGROUND: Ledipasvir (LDV)/sofosbuvir (SOF) has demonstrated high efficacy,
safety, and tolerability in hepatitis C virus (HCV)-infected patients. There is
limited data, however, regarding the optimal timing of therapy in the context of
possible liver transplantation (LT). METHODS: We compared the cost-effectiveness
of 12 weeks of HCV therapy before or after LT or nontreatment using a decision
analytical microsimulation state-transition model for a simulated cohort of 10
000 patients with HCV Genotype 1 or 4 with Child B or C cirrhosis. All model
parameters regarding the efficacy of therapy, adverse events and the effect of
therapy on changes in model for end-stage liver disease (MELD) scores were
derived from the SOLAR-1 and 2 trials. The simulations were repeated with 10 000
samples from the parameter distributions. The primary outcome was cost (2014 US
dollars) per quality adjusted life year. RESULTS: Treatment before LT yielded
more quality-adjusted life year for less money than treatment after LT or
nontreatment. Treatment before LT was cost-effective in 100% of samples at a
willingness-to-pay threshold of US $100 000 in the base-case and when the
analysis was restricted to Child B alone, Child C, or MELD > 15. Treatment before
transplant was not cost-effective when MELD was 6-10. In sensitivity analyses,
the MELD after which treatment before transplant was cost-effective was 13 and
the maximum cost of LDV/SOF therapy at which treatment before LT is cost
effective is US $177 381. CONCLUSIONS: From a societal perspective, HCV therapy
using LDV/SOF with ribavirin before LT is the most cost-effective strategy for
patients with decompensated cirrhosis and MELD score greater than 13.
PMID- 27495756
TI - Evaluation of Microvascular Inflammation in ABO-Incompatible Kidney
Transplantation.
AB - BACKGROUND: In ABO-incompatible kidney transplantation, the diagnostic criteria
for antibody-mediated rejection remain controversial because C4d deposition is
commonly observed. Thus, we investigated microvascular inflammation (MVI score >=
2) within 1 year as a predictor of graft outcome. METHODS: A total of 148
recipients without preformed or de novo donor-specific anti-HLA antibody were
stratified based on MVI score less than 2 (n = 117) and MVI score of 2 or greater
(n = 31). RESULTS: We found that 5-year graft survival was significantly lower (P
= 0.0129) in patients with MVI (89.8%) than in patients without MVI (97.0%).
Graft function, as characterized by serum estimated glomerular filtration rate,
was also significantly worse for patients with MVI than it was for patients
without MVI, between 3 months and 10 years after transplantation (P = 0.048).
Multivariate analysis indicated that HLA class II mismatch (P = 0.0085) was an
independent marker of MVI. CONCLUSIONS: Microvascular inflammation score of 2 or
greater is significantly associated with poor graft outcome after ABO
incompatible kidney transplantation. We suggest that MVI score of 2 or greater in
ABOi transplantation be used as a basis to diagnose antibody-mediated rejection.
PMID- 27495757
TI - Organ Transplantation in Mexico.
PMID- 27495758
TI - Survival Benefit in Older Patients Associated With Earlier Transplant With High
KDPI Kidneys.
AB - BACKGROUND: Given high dialysis mortality rates for patients older than 60 years,
accepting a kidney with a high Kidney Donor Profile Index (KDPI) score could
enable earlier and potentially preemptive transplantation (preKT). However,
evidence regarding the risks of high KDPI allografts in older patients is
limited. Our objective was to determine the relative benefit for older patients
of KDPI greater than 85% transplant either preemptively or not compared with
remaining on the waitlist. METHODS: United Network of Organ Sharing data from
2003 to 2012 for adult deceased donor kidney transplant candidates was analyzed
to evaluate patient survival in patients older than 60 years for preKT and non
preKT KDPI greater than 85% transplants compared with candidates remaining on the
waitlist including patients who received KDPI 0% to 85% transplants according to
multivariate Cox regression models. RESULTS: In the first year posttransplant for
KDPI greater than 85% of transplants in recipients older than 60 years, preKT had
a reduced mortality hazard (hazards ratio [HR], 0.61; 95% confidence interval
[95% CI], 0.41-0.90) and non-preKT an increased mortality hazard (HR, 1.15; 95%
CI, 1.03-1.27) compared with the waitlist including KDPI 0% to 85% transplant
recipients. At 1 to 2 years and after 2 years, both KDPI greater than 85% groups
had significant reductions in mortality (1-2 years: preKT HR, 0.38; 95% CI, [0.23
0.60] and non-preKT HR, 0.52; 95% CI, 0.45-0.61; and 2+ years: preKT HR, 0.50;
95% CI, 0.38-0.66 and non-preKT HR, 0.64; 95% CI, 0.58-0.70, respectively).
CONCLUSIONS: PreKT and non-preKT KDPI greater than 85% transplant was associated
with lower mortality hazard after the first year compared with the waitlist
including KDPI 0% to 85% transplants in patients older than 60 years. Further
consideration should be given to increased utilization of high KDPI grafts in
older patients with the goal of avoiding or limiting time on dialysis.
PMID- 27495759
TI - Use of HCV+ Donors Does Not Affect HCV Clearance With Directly Acting Antiviral
Therapy But Shortens the Wait Time to Kidney Transplantation.
AB - BACKGROUND: Hepatitis C virus (HCV) infection is prevalent in the renal
transplant population but direct acting antiviral agents (DAA) provide an
effective cure of HCV infection without risk of allograft rejection. METHODS: We
report our experience treating 43 renal transplant recipients with 4 different
DAA regimens. RESULTS: One hundred percent achieved a sustained viral response by
12 weeks after therapy, and DAA regimens were well tolerated. Recipients
transplanted with a HCV+ donor responded equally well to DAA therapy those
transplanted with a kidney from an HCV- donor, but recipients of HCV+ organs
experienced significantly shorter wait times to transplantation, 485 days
(interquartile range, 228-783) versus 969 days (interquartile range, 452-2008; P
= 0.02). CONCLUSIONS: On this basis, we advocate for a strategy of early
posttransplant HCV eradication to facilitate use of HCV+ organs whenever
possible. Additional studies are needed to identify the optimal DAA regimen for
kidney transplant recipients, accounting for efficacy, timing relative to
transplant, posttransplant clinical outcomes, and cost.
PMID- 27495760
TI - A Call for Research on Individuals Who Opt Out of Living Kidney Donation:
Challenges and Opportunities.
AB - In light of the transplant community's efforts to increase living donation,
preserving donor autonomy is essential. Understanding how often and the reasons
why potential living kidney donors opt out of the donor evaluation process for
nonmedical reasons is important for assessing donor voluntariness. The
experiences of individuals who opt out of donation may reveal avenues for
enhancing donor protections and identify modifiable deterrents to donation. A
limited number of centers have reported rates of opting out between 0.2% and 22%;
the reasons for declining to donate are not well studied. This article calls for
further research on potential living donors who opt out of donation. We describe
challenges to studying this population and offer a roadmap for an ethical
approach to conducting research on individuals who withdraw from living kidney
donor evaluation.
PMID- 27495761
TI - Delayed Graft Function Phenotypes and 12-Month Kidney Transplant Outcomes.
AB - BACKGROUND: Ischemia-reperfusion injury (IRI) leading to delayed graft function
(DGF), defined by the United Network for Organ Sharing as dialysis in the first
week (UNOS-DGF), associates with poor kidney transplant outcomes. Controversies
remain, however, about dialysis initiation thresholds and the utility for other
criteria to denote less severe IRI, or slow graft function (SGF). METHODS:
Multicenter, prospective study of deceased-donor kidney recipients to compare
UNOS-DGF to a definition that combines impaired creatinine reduction in the first
48 hours or greater than 1 dialysis session for predicting 12-month estimated
glomerular filtration rate (eGFR). We also assessed 10 creatinine and urine
output-based SGF definitions relative to 12-month eGFR. RESULTS: In 560
recipients, 215 (38%) had UNOS-DGF, 330 (59%) met the combined definition, 14
(3%) died, and 23 (4%) had death-censored graft failure by 12 months. Both DGF
definitions were associated with lower adjusted 12-month eGFR (95% confidence
interval)-by 7.3 (3.6-10.9) and 7.4 (3.8-11.0) mL/min per 1.73 m, respectively.
Adjusted relative risks for 12-month eGFR less than 30 mL/min per 1.73 m were 1.9
(1.2-3.1) and 2.1 (1.1-3.7), with unadjusted areas under the curve of 0.618 and
0.627, respectively. For SGF definitions, postoperative day (POD) 7 creatinine
had the strongest association with 12-month eGFR, and POD5 creatinine and
creatinine reduction between POD1 and POD2 demonstrated modest separations in 12
month eGFR. CONCLUSIONS: Although UNOS-DGF does not adequately predict 12-month
function on its own, our findings do not support changing the definition.
Postoperative day 7 creatinine is correlated with 12-month eGFR, but large
translational studies are needed to understand the biological link between IRI
severity at transplant and longer-term outcomes.
PMID- 27495762
TI - Graft Versus Host Disease After Liver Transplantation in Adults: A Case series,
Review of Literature, and an Approach to Management.
AB - BACKGROUND: Graft-versus-host-disease (GVHD) after liver transplantation (LT) is
a deadly complication with very limited data on risk factors, diagnosis and
management. We report a case series and a comprehensive review of the literature.
METHODS: Data were systematically extracted from reports of GVHD after LT, and
from the United Network for Organ Sharing database. Group comparisons were
performed. RESULTS: One hundred fifty-six adult patients with GVHD after LT have
been reported. Median time to GVHD onset was 28 days. Clinical features were skin
rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD
after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter
bacteremia, invasive aspergillosis, and disseminated Candida infections were
frequently reported. Recipient age over 50 years is a risk factor for GVHD after
LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was
underrepresented, in reported United States GVHD cases relative to all United
Network for Organ Sharing database LT cases. Mortality rate with treatment of
GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens
using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists.
Mortality was 25% in small case series using the CD2-blocker alefacept or TNF
alpha antagonists. CONCLUSIONS: Age older than 50 years and hepatocellular
carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High
dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD
after LT. CD2-blockers and TNF-alpha antagonists appear promising. We propose a
diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.
PMID- 27495764
TI - How to Perform Selective Liver Biopsy in Living Liver Donors Using Plain Computed
Tomography.
AB - BACKGROUND: Preoperative donor liver biopsy is the criterion standard to verify
the quality of a liver. However, it can cause some complications, thus this study
was designed to know whether selective liver biopsy is possible or not, and to
find a subgroup that does not require preoperative biopsy. METHODS: We reviewed
preoperative images and postoperative outcome in 118 donors from September 2013
to January 2014. Visual grading of steatosis on plain computed tomography (CT)
was performed and compared steatosis on preoperative liver biopsy was done within
7 days from the CT scan. RESULTS: Visual grades of plain CT were 1 (n = 50,
42.4%), 2 (n = 47, 39.8%), 3 (n = 13, 11.0%), 4 (n = 7, 5.9%), and 1 (n = 1,
0.8%). Macrovesicular steatosis on liver biopsy according to visual grades were 1
(0.67 +/- 1.3%), 2 (1.67 +/- 1.8%), 3 (6.23 +/- 6.4%), 4 (14.7 +/- 16.6), and 5
(30%). Right liver grafts including right lobe, modified right lobe, and extended
right lobe were procured in 106 (89.9%) donors, and 16% (17/106) of the donors
were visual grades 3, 4, and 5. Eleven donors (64.7%) were accepted for right
liver donation after liver biopsy, whereas 6 (35.3%) donors were deemed possible
to donate right liver after weight reduction and reevaluation of steatosis.
Transient hepatic dysfunction after right hepatectomy was significantly increased
according to the increment of visual grade. CONCLUSIONS: Preoperative liver
biopsy may not be necessary in visual grade 1 or 2 donors, but should be
performed for grade 3 and 4 donors based on recipient's urgency so as to decide
whether to proceed with right hepatectomy or not.
PMID- 27495765
TI - Proposal of Muscle-MELD Score, Including Muscularity, for Prediction of Mortality
After Living Donor Liver Transplantation.
AB - BACKGROUND: The Model for End-stage Liver Diseases (MELD) is currently the most
widely accepted scoring system for predicting prognosis and for allocation of
liver grafts in patients awaiting liver transplantation (LT). However, this
system is independent of the severity of recipient nutritional and functional
status. METHODS: The present study retrospectively evaluated the preoperative
quality and quantity of skeletal muscle in 231 adult patients undergoing living
donor LT (LDLT) between January 2008 and December 2014. Using plain computed
tomography imaging at the third lumbar vertebral level, the preoperative
muscularity (quantity and quality of skeletal muscle) was evaluated. We included
muscularity with the MELD score (Muscle-MELD) and investigated its ability to
predict posttransplant mortality. RESULTS: Cox regression analysis provided the
following equation for Muscle-MELD: Muscle-MELD = MELD score + 27.0 * low muscle
quality + 25.2 * low muscle mass. The overall survival rate after LDLT was
significantly lower in patients with high Muscle-MELD than in patients with low
Muscle-MELD scores (P < 0.001). Muscle-MELD scores more accurately predicted
posttransplant mortality than conventional MELD scores (P = 0.038 for 3 months, P
= 0.002 for 6 months, P < 0.001 for 12 months, and P = 0.001 for overall
mortality). With multivariate analysis, high Muscle-MELD score was an independent
predictor of 6-month mortality after LDLT (odds ratio, 6.715; 95% confidence
interval, 3.305-14.653; P < 0.001). CONCLUSIONS: Muscle-MELD score closely
correlates with posttransplant mortality. Our results suggest that perioperative
nutritional intervention and rehabilitation would affect posttransplant outcomes
with improving pretransplant low muscularity.
PMID- 27495763
TI - A20 Haploinsufficiency Aggravates Transplant Arteriosclerosis in Mouse Vascular
Allografts: Implications for Clinical Transplantation.
AB - BACKGROUND: Inflammation is central to the pathogenesis of transplant
arteriosclerosis (TA). We questioned whether physiologic levels of anti
inflammatory A20 influence TA severity. METHODS: We performed major
histocompatibility complex mismatched aorta to carotid artery interposition
grafts, using wild type (WT) or A20 heterozygote (HET) C57BL/6 (H-2) donors and
BALB/c (H-2) recipients, and conversely BALB/c donors and WT/HET recipients. We
analyzed aortic allografts by histology, immunohistochemistry,
immunofluorescence, and gene profiling (quantitative real-time reverse
transcriptase polymerase chain reaction). We validated select in vivo A20 targets
in human and mouse smooth muscle cell (SMC) cultures. RESULTS: We noted
significantly greater intimal hyperplasia in HET versus WT allografts, indicating
aggravated TA. Inadequate upregulation of A20 in HET allografts after
transplantation was associated with excessive NF-kB activation, gauged by higher
levels of IkBalpha, p65, VCAM-1, ICAM-1, CXCL10, CCL2, TNF, and IL-6 (mostly
localized to SMC). Correspondingly, cytokine-induced upregulation of TNF and IL-6
in human and mouse SMC cultures inversely correlated with A20 expression.
Aggravated TA in HET versus WT allografts correlated with increased intimal SMC
proliferation, and a higher number of infiltrating IFNgamma and Granzyme B CD4 T
cells and natural killer cells, and lower number of FoxP3 regulatory T cells. A20
haploinsufficiency in allograft recipients did not influence TA. CONCLUSIONS: A20
haploinsufficiency in vascular allografts aggravates lesions of TA by
exacerbating inflammation, SMC proliferation, and infiltration of pathogenic T
cells. A20 single nucleotide polymorphisms associating with lower A20 expression
or function in donors of vascularized allografts may inform risk and severity of
TA, highlighting the clinical implications of our findings.
PMID- 27495766
TI - Non-HLA Antibodies May Accelerate Immune Responses After Intestinal and
Multivisceral Transplantation.
AB - BACKGROUND: Non-HLA alloantibodies and autoantibodies are involved in allograft
rejection in kidney and heart transplantation. Their role in intestinal
transplantation has not yet been described. We examined the development of
antiangiotensin II type I receptor antibodies (anti-AT1R) and antiendothelin type
A receptor antibodies associated with the clinical course and histopathological
findings of intestinal transplantation recipients. METHODS: Thirty-seven patients
underwent intestinal or multivisceral transplantation. Non-HLA antibodies (non
HLAabs) were screened in 29 transplant recipients. Antibody-levels greater than
12 U/L were considered positive and were evaluated retrospectively regarding
rejection episodes. RESULTS: Twenty patients developed anti-AT1R and/or
antiendothelin type A receptor antibodies (non-HLAabs group), 9 did not (control
group). The non-HLAabs group had a higher rate of allograft rejection than
controls (80% vs 55%), especially a higher rate of antibody-mediated rejections
(55% vs 11%, P < 0.01) with detection of donor-specific anti-HLAabs. All
rejection episodes in the non-HLAabs group appeared around the time of positive
non-HLAabs detection. Five patients had acute cellular rejections at the time of
non-HLAabs development, 4 had viral infections. CONCLUSIONS: Our data suggest
that antibody-mediated mechanisms targeting antigens beyond HLA may trigger and
accelerate immune responses. Given the possibility of pharmacologic targeting of
non-HLA receptors, future studies will focus on the explanation of mechanisms how
non-HLAabs may enhance rejection and affect long-term allograft survival.
PMID- 27495767
TI - Transplant Arteriosclerosis.
PMID- 27495770
TI - Successful Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and
Ledipasvir in Renal Transplant Recipients.
AB - BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection after renal
allograft transplantation has been an obstacle because of contraindications
associated with IFN-based therapies. Direct-acting antiviral agents are highly
efficient treatment options that do not require IFN and may not require
ribavirin. Therefore, we assessed the efficacy and safety of sofosbuvir and
ledipasvir in renal transplant patients with chronic HCV infection. METHODS:
Fifteen renal allograft recipients with therapy-naive HCV genotype (GT) 1a, 1b,
or 4 were treated with the combination of sofosbuvir and ledipasvir without
ribavirin for 8 or 12 weeks. Clinical data were retrospectively analyzed for
viral kinetics and for renal and liver function parameters. Patients were closely
monitored for trough levels of immunosuppressive agents, laboratory values, and
potential adverse effects. RESULTS: Ten patients (66%) exhibited a rapid
virologic response within 4 weeks (HCV GT1a, n = 4; HCV GT1b, n = 6). The other 5
patients exhibited a virologic response within 8 (HCV GT 1b, n = 4) or 12 weeks
(HCV GT4, n = 1). One hundred percent of patients exhibited sustained virologic
response at week 12 after the end of treatment. Clinical measures of liver
function improved substantially for all patients. Adverse events were scarce;
renal transplant function and proteinuria remained stable. Importantly, dose
adjustments for tacrolimus were necessary for maintaining sufficient trough
levels. CONCLUSIONS: The described regimen appears to be safe and effective for
patients after renal transplant and is a promising treatment regimen for
eradicating HCV in this patient population.
PMID- 27495768
TI - Use of Everolimus in Liver Transplantation: Recommendations From a Working Group.
AB - Immunosuppression after liver transplantation (LT) is presently based on use of
calcineurin inhibitors (CNI), although they are associated with an increased
incidence of renal dysfunction, cardiovascular complications, and de novo and
recurrent malignancies. Over the past decade, mammalian target of rapamycin
inhibitors have received considerable attention as immunosuppressants because
they are associated with a more favorable renal profile versus CNI, as well as
antiproliferative activity in clinical studies. Comprehensive guidelines on use
of everolimus (EVR) in LT are still lacking. In Italy, a project, named
Everolimus: the road to long-term functioning, was initiated to collect the
experience on EVR after LT with the aim of providing guidance for transplant
clinicians. Herein, recommendations by this national consensus group, based on
Delphi methodology, are presented. Consensus was reached on 20 of the 23
statements proposed, and their level of evidence, grade of recommendation, and
percent of agreement are reported. Statements are grouped into 4 areas: (A) renal
function; (B) time of EVR introduction, CNI reduction and elimination, and risk
for graft rejection; (C) antiproliferative effects of EVR; and (D) management of
EVR-related adverse events. The high level of consensus shows that there is good
agreement on the routine use of EVR in predefined clinical scenarios, especially
in light of posttransplant nephrotoxicity and other adverse events associated
with long-term administration of CNIs.
PMID- 27495772
TI - Histological and Extended Clinical Outcomes After ABO-Incompatible Renal
Transplantation Without Splenectomy or Rituximab.
AB - BACKGROUND: Excellent short-term results have been reported in ABO-incompatible
(ABOi) renal transplant recipients managed solely with antibody removal and
conventional immunosuppression. However, long-term clinical outcomes with this
regimen and predictive information from protocol biopsies are lacking. METHODS:
We compared outcome data in ABOi and ABO-compatible (ABOc) recipients receiving
this regimen approximately 4 years posttransplant, and histology from biopsies
approximately 12 months posttransplant. RESULTS: Patient and graft survivals
among 54 ABOi recipients were 98.1% and 90.7%, respectively, at 4 years. Graft
function was similar between ABOi (creatinine, 140.3 MUmol/L) and ABOc recipients
(creatinine, 140.2 MUmol/L) (P = 0.99), with no significant change over the study
period in either group (Deltacreatinine, -0.83 vs 6.6 MUmol/L) (P = 0.59). There
was no transplant glomerulopathy in biopsies from either group. Interstitial
fibrosis (IF) and tubular atrophy (TA) was present in 7 (28%) of 25 ABOi compared
with 7 (20.6%) of 34 ABOc (P = 0.52). Progression of IF/TA from implantation was
noted in 6 (24%) of 25 ABOi and 6 (17.6%) of 34 ABOc, respectively. C4d staining
without antibody-mediated rejection was present in 13 (52%) 25 early
posttransplant biopsies from ABOi recipients by immunohistochemistry, but in only
4 (16%) of 25 at 12 months. CONCLUSIONS: ABO-incompatible renal transplant
performed with antibody removal and conventional immunosuppression continues to
provide excellent patient and graft survival, and stable renal function over 4
years. Coupled with absent transplant glomerulopathy and low rates of progressive
IF/TA on earlier biopsies, this suggests that ABOi with conventional
immunosuppression and antibody removal, without rituximab or splenectomy, can
achieve long-term outcomes comparable to ABO-compatible transplantation.
PMID- 27495773
TI - Safety and Efficacy of Alemtuzumab Induction in Highly Sensitized Pediatric Renal
Transplant Recipients.
AB - BACKGROUND: Studies show that alemtuzumab, a potent lymphocyte-depleting agent,
is well tolerated in pediatric renal transplantation. We report on the use of
alemtuzumab induction in highly HLA sensitized (HS) pediatric kidney transplant
patients. METHODS: Fifty pediatric renal transplants were performed from 1/2009
12/2014. 15 HS patients received IVIG (2 g/kg *2 doses)/rituximab (375 mg/m *1)
for desensitization with alemtuzumab induction (15-30 mg, 1 dose, subcutaneous),
whereas 35 nonsensitized patients received anti-IL-2R. Graft survival and
infections were compared between 2 groups. RESULTS: All HS patients had received
a prior transplant and were older with lower risk for viral infections due to
serostatus. Patient survival was 100%, and graft outcomes were similar with mean
1-year creatinine of 1.03 +/- 0.45 versus 0.99 +/- 0.6 (P = 0.48). Although a
higher incidence of acute cellular rejection was seen in HS patients receiving
alemtuzumab (P = 0.001), there was a nonsignificant difference in antibody
mediated rejection. White blood cell and absolute lymphocyte count were
significantly lower in alemtuzumab group at 30 days (P < 0.0001) and at 1 year (P
= 0.026 and P = 0.001), respectively. There was no significant difference in
bacterial, viral, or fungal infections after transplant. CONCLUSIONS: Alemtuzumab
induction with desensitization led to nearly equivalent graft survival and
functional outcomes in HS pediatric patients as nonsensitized patients receiving
anti-IL-2R induction. With this small sample size, we observed significant
reduction of white blood cell and absolute lymphocyte count up to 1 year
posttransplant. The risk of infection was comparable between the 2 groups;
however, patients who received alemtuzumab were older and at lower risk of viral
infection due to serostatus.
PMID- 27495774
TI - Sequential Use of Normothermic Regional Perfusion and Hypothermic Machine
Perfusion in Donation After Cardiac Death Liver Transplantation With Extended
Warm Ischemia Time.
PMID- 27495776
TI - Conformational Variants of the Individual HLA-I Antigens on Luminex Single
Antigen Beads Used in Monitoring HLA Antibodies: Problems and Solutions.
AB - BACKGROUND: Single antigen beads (SAB) are used for monitoring HLA antibodies in
pretransplant and posttransplant patients despite the discrepancy between virtual
and actual crossmatch results and transplant outcomes. This discrepancy can be
attributed to the presence of conformational variants of HLA-I on SAB, assessment
of which would increase the concordance between SAB and flow cytometry crossmatch
(FCXM) results, thus enabling improved organ accessibility for the waiting list
patients and a better prediction of antibody-mediated rejection. METHODS: The
conformational variants were examined on HLA-I beads, iBeads, acid-/alkali
treated beads, and T cells using HLA-I monoclonal antibodies (W6/32, TFL-006, and
heavy chain (HC)-10). RESULTS: The affinity of the monoclonal antibodies against
HLA-I beads confirmed the presence and heterogeneous density of peptide
associated beta2-microglobulin-associated HLA HC (pepA-beta2aHC), peptide-free
beta2aHC (pepF-beta2aHC), and beta2-free HC (beta2fHC) on every single antigen
coated bead. In contrast, iBeads harbor a high density of pepA-beta2aHC, low
density of pepF-beta2aHC, and are lacking beta2fHC. The FCXM analyses confirmed
the prevalence of pepA-beta2aHC, but not pepF-beta2aHC or beta2fHC on resting T
cells. CONCLUSIONS: The strength of a donor-specific antibody should be assessed
with a bead-specific mean fluorescence intensity cutoff based on TFL-006
reactivity against HLA-I beads, and HC-10 against iBeads, where the beta2fHC or
pepF-beta2aHC normalized donor-specific antibody level would reveal the true anti
pepA-beta2aHC reactivity associated with positive FCXM.
PMID- 27495775
TI - Outcomes in Transplant Recipients Treated With Foscarnet for Ganciclovir
Resistant or Refractory Cytomegalovirus Infection.
AB - BACKGROUND: Antiviral-resistant or refractory cytomegalovirus (CMV) infection is
challenging, and salvage therapies, foscarnet, and cidofovir, have significant
toxicities. Several investigational anti-CMV agents are under development, but
more information is needed on outcomes of current treatments to facilitate
clinical trial design for new drugs. METHODS: Records of solid organ transplant
(SOT) and hematopoietic cell transplant (HCT) recipients at a single center over
a 10-year period were reviewed retrospectively to characterize those who had
received foscarnet treatment for ganciclovir-resistant or refractory CMV
infection. Data were collected on virologic responses, mortality, and
nephrotoxicity. RESULTS: Of 39 patients (22 SOT, 17 HCT), 15 had documented
ganciclovir resistance mutations and 11 (28%) of 39 had tissue-invasive CMV.
Median duration of foscarnet was 32 days. Virologic failure occurred in 13 (33%)
of 39 and relapses of viremia occurred in 31%. Mortality was 12 (31%) of 39 and
was higher in HCT than SOT (P = 0.001), although ganciclovir resistance was more
common in SOT (P = 0.003). Doses of ganciclovir or valganciclovir were low in 10
(26%) of 39 at some time before switching to foscarnet. Renal dysfunction
occurred in 20 (51%) of 39 by end of treatment and in 7 (28%) of 25 after 6
months. CONCLUSIONS: Outcomes of existing treatment for ganciclovir-resistant or
refractory CMV are suboptimal, in terms of virologic clearance, renal
dysfunction, and mortality. These data should provide background information for
future clinical trials of newer antiviral agents.
PMID- 27495778
TI - The Authors' Reply.
PMID- 27495779
TI - Radiofrequency ablation for HCC patients with multifocal tumours meeting the
Milan criteria: A single-centre experience.
AB - BACKGROUND: Radiofrequency ablation (RFA) has been recommended as a curative
treatment for patients with single early-stage unifocal hepatocellular carcinomas
(HCCs) for years; however, the effect of this treatment on multifocal tumours has
remained uncertain. AIMS: We conducted a retrospective study to evaluate the
overall survival (OS) and recurrence-free survival (RFS) rates of early HCC
patients with multiple tumours subjected to different RFA modalities. METHODS:
One hundred fifty-four HCC patients with multifocal tumours who met the Milan
criteria and underwent RFA were enrolled in this study. We divided the patients
into 3 groups according to the surgical approach utilised (percutaneous,
laparoscopic and open RFA; selection was based on the locations of the tumours
for whether they were adhered to the subhepatic inferior vena cava or the
gastrointestinal tract) and into 2 subgroups according to the tumour numbers and
locations. RESULTS: No deaths occurred in the 30-day post-operation period, and
there were no significant differences in the complication, OS or RFS rates
between the 3 groups. The 1-, 3- and 5-year OS rates were 88.9%, 75.5% and 50.9%
in the subgroup with 2 tumours, respectively, versus 91.3%, 56.3% and 17.5% in
the subgroup with 3 tumours, respectively (P=0.001). The corresponding values
were 93.2%, 77.4% and 50.8% in the subgroup with tumours in the same segment and
82.4%, 54.8% and 23.0% in the subgroup with tumours in different segments
(P=0.001). CONCLUSION: RFA was proven to be an effective and safe method for the
treatment of multifocal HCCs. Among the patients with 2 tumours within the same
segment, RFA achieved better long-term outcomes in terms of both overall and
recurrence-free survival.
PMID- 27495780
TI - A quick glance at selected topics in this issue.
AB - A quick glance at selected topics in this issue aims to highlight selected
articles and provide a quick review to the reader.
PMID- 27495781
TI - Detecting papillary neovascularization in proliferative diabetic retinopathy
using optical coherence tomography angiography.
PMID- 27495782
TI - Integrative analysis of metabolome and gut microbiota in diet-induced
hyperlipidemic rats treated with berberine compounds.
AB - BACKGROUND: Hyperlipidemia is a major component of metabolic syndrome, and often
predicts cardiovascular diseases. We developed a new therapeutic agent berberine
compounds (BC), consisting of berberine, oryzanol and vitamin B6, and determined
their anti-hyperlipidemia activity and underlying mechanisms. METHODS: Male
Wistar rats were fed a high fat diet (HFD) to induce hyperlipidemia, and then
given BC orally for 4 weeks. Body weight and food intake were recorded weekly,
and lipid profiles in serum were determined biochemically. Metabolites in serum,
urine, liver and feces were analyzed by GC-MS, and the structure of microbiota
was determined by 16S rDNA sequencing. RESULTS: Lipid lowering was observed in
the hyperlipidemic rats upon BC treatment without apparent adverse side effects.
Metabolomics analysis indicated that the BC treatment resulted in increased
pyruvic acid, serotonin, and ketogenic and glycogenic amino acid levels in the
serum, increased pyridoxine and 4-pyridoxic acid in the urine, decreased
hypotaurine and methionine in the liver, and increased putrescine and decreased
deoxycholate and lithocholate in feces. The BC treatment also resulted in an
enrichment of beneficial bacteria (e.g. Bacteroides, Blautia) and a decrease in
Escherichia. CONCLUSIONS: The lipid lowering effect of BC treatment in
hyperlipidemic rats is associated with a global change in the metabolism of
lipids, carbohydrates and amino acids, as well as the structure of microbiota.
PMID- 27495783
TI - Risk Factors of Physical and Sexual Abuse for Women in Mali: Findings From a
Nationally Representative Sample.
AB - Mali is a developing country that has marked inequalities between genders. Using
the 2012-2013 Mali Demographic and Health Survey, a nationally representative
sample of Malian women ( N = 2,527), the study examined the effect of controlling
behaviors, childhood exposure to and experience of violence, husband's alcohol
use, woman's use of violence, and sociocultural factors on the likelihood of
experiencing physical and sexual abuse. Findings indicated that controlling
behavior, childhood exposure to violence, and husband's use of alcohol were
predictors of physical and sexual abuse. Respondent's use of violence increased
risk of physical abuse. Implications for programming in Mali are discussed.
PMID- 27495784
TI - [Pathology of lung cancer].
AB - Lung cancer is the leading cause of cancer death in men and the second most
frequent cause in women. The pathology of lung tumors is of special relevance
concerning therapy and prognosis and current classification systems have to be
taken into consideration. The results of molecular tissue subtyping allow further
classification and therapeutic options. The histological entities are mainly
associated with typical X-ray morphological features.
PMID- 27495785
TI - [Radiological knowledge management with the help of departmental wikis].
AB - In times of RIS (radiology information system) and KIS (hospital information
system) systems, patient-related data are at the radiologist's disposal at the
push of a button. However, this is not the case for other important data. The
increasing complexity of modern medicine demands that up-to-date information like
protocols, SOPs (Standards of Practice), news and modifications are constantly
accessible to all employees. This aspect of quality assurance becomes
increasingly important in the context of certification. For such knowledge
management purposes we have built a wiki in our department. Here we report our
positive experiences with this technology.
PMID- 27495786
TI - [Lung cancer screening - risk stratification : Who should undergo screening?].
AB - Lung cancer is one of the leading causes of deaths in Europa and the USA. In
approximately 75 % of lung cancer patients, bronchogenic carcinoma is detected at
an advanced tumor stage; therefore, therapeutic options which aim at curing the
disease in these patients are limited and treatment is mostly palliative. A
relatively good prognosis is reserved for the minority of patients where the
tumor is detected at an early stage and treatment is potentially curative. For
this reason, early diagnosis of lung cancer could save lives. Retrospective
analyses of the US national lung screening trial (NLST) showed that especially
high-risk populations (e. g. higher age, positive smoking history, overweight and
a positive family history for lung cancer) benefit most from lung cancer
screening. Thus, the effectiveness of computed tomography (CT) screening can be
improved by focusing on high-risk populations. This review article summarizes the
risk stratification models of the large European and American screening studies
and discusses possible future biomarkers for risk stratification.
PMID- 27495787
TI - [Diagnostic work-up of pulmonary nodules : Management of pulmonary nodules
detected with low-dose CT screening].
AB - Pulmonary nodules are the most frequent pathological finding in low-dose computed
tomography (CT) scanning for early detection of lung cancer. Early stages of lung
cancer are often manifested as pulmonary nodules; however, the very commonly
occurring small nodules are predominantly benign. These benign nodules are
responsible for the high percentage of false positive test results in screening
studies. Appropriate diagnostic algorithms are necessary to reduce false positive
screening results and to improve the specificity of lung cancer screening. Such
algorithms are based on some of the basic principles comprehensively described in
this article. Firstly, the diameter of nodules allows a differentiation between
large (>8 mm) probably malignant and small (<8 mm) probably benign nodules.
Secondly, some morphological features of pulmonary nodules in CT can prove their
benign nature. Thirdly, growth of small nodules is the best non-invasive
predictor of malignancy and is utilized as a trigger for further diagnostic work
up. Non-invasive testing using positron emission tomography (PET) and contrast
enhancement as well as invasive diagnostic tests (e.g. various procedures for
cytological and histological diagnostics) are briefly described in this article.
Different nodule morphology using CT (e.g. solid and semisolid nodules) is
associated with different biological behavior and different algorithms for follow
up are required. Currently, no obligatory algorithm is available in German
speaking countries for the management of pulmonary nodules, which reflects the
current state of knowledge. The main features of some international and American
recommendations are briefly presented in this article from which conclusions for
the daily clinical use are derived.
PMID- 27495788
TI - Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows
sex-divergent effects on the tissue uptake and distribution pattern of sunitinib
in mice.
AB - PURPOSE: Pharmacokinetic interaction of sunitinib with diclofenac, paracetamol,
mefenamic acid and ibuprofen was evaluated due to their P450 mediated metabolism
and OATP1B1, OATP1B3, ABCB1, ABCG2 transporters overlapping features. METHODS:
Male and female mice were administered 6 sunitinib doses (60 mg/kg) PO every 12 h
and 30 min before the last dose were administered vehicle (control groups), 250
mg/kg paracetamol, 30 mg/kg diclofenac, 50 mg/kg mefenamic acid or 30 mg/kg
ibuprofen (study groups), euthanized 6 h post last administration and sunitinib
plasma, liver, kidney, brain concentrations analyzed. RESULTS: Ibuprofen halved
sunitinib plasma concentration in female mice (p < 0.01) and showed 59 % lower
concentration than male mice (p < 0.05). Diclofenac and paracetamol female mice
showed 45 and 25 % higher plasma concentrations than male mice which were 27 %
lower in mefenamic acid female mice. Paracetamol increased 2.2 (p < 0.05) liver
and 1.4-fold (p < 0.05) kidney sunitinib concentrations in male mice that were
lower in female mice (p < 0.01, p < 0.001, respectively). Ibuprofen increased 2.9
fold (p < 0.01) liver concentration in male mice that were higher than in female
mice (p < 0.001). Female control mice had 35 % higher sunitinib brain
concentration than male mice but the concentration decreased 37, 33, 10 and 57 %
in the diclofenac, paracetamol, mefenamic acid and ibuprofen (p < 0.001),
respectively. Tissue-plasma concentrations correlations were nonsignificant in
control, paracetamol, mefenamic acid and ibuprofen groups but was significant in
the diclofenac group in male mice (liver, brain) and female mice (liver, kidney).
CONCLUSIONS: These results portray gender-based sunitinib pharmacokinetic
differences and NSAIDs selective effects on male or female mice, with potential
clinical translatability.
PMID- 27495789
TI - Reply to timing and type of immune checkpoint therapy affect the early
radiographic response of melanoma brain metastases to stereotactic radiosurgery.
PMID- 27495790
TI - A single mechanism driving both inactivation and adaptation in rapidly adapting
currents of DRG neurons?
AB - Rapidly adapting (RA) currents expressed in dorsal root ganglia somatosensory
neurons reduce their amplitude in response to prolonged and/or repeated
mechanical stimulation. Both inactivation of mechanotransducer channels and
adaptation of the force acting on the channels have been suggested to
independently decrease RA currents. However, these two mechanisms have similar
kinetics and dependence on calcium and voltage. These experimental findings
suggest that a single mechanism might underlie both. We constructed a simple
Hodgkin-Huxley-type model with a single gating variable driving both inactivation
and adaptation to test this hypothesis. Predictions of the model successfully
describe key features of mechanical activation as well as inactivation,
adaptation, and recovery. The model thus supports the possibility of a single
mechanism driving inactivation and adaptation in RA currents. On its own, the
model can be integrated into higher-order models of touch receptors because of
its accurate simulation of RA currents.
PMID- 27495791
TI - Environmental Enteropathy: Elusive but Significant Subclinical Abnormalities in
Developing Countries.
AB - Environmental enteropathy/Environmental enteric dysfunction (EE/EED) is a chronic
disease of small intestine characterized by gut inflammation and barrier
disruption, malabsorption and systemic inflammation in the absence of diarrhea.
It is predominantly diseases of children in low income countries and is
hypothesized to be caused by continuous exposure to fecally contaminated food,
water and fomites. It had not been recognized as a priority health issue because
it does not cause overt symptoms and was seen in apparently healthy individuals.
However, there is a growing concern of EE/EED because of its impact on
longitudinal public health issues, such as growth faltering, oral vaccine low
efficacy and poor neurocognitive development. Recent works have provided
important clues to unravel its complex pathogenesis, and suggest possible
strategies for controlling EE/EED. However, effective diagnostic methods and
interventions remain unsettled. Here, we review the existing literature,
especially about its pathogenesis, and discuss a solution for children living in
the developing world.
PMID- 27495792
TI - Clevidipine-induced Dyspnea Relief in Acute Heart Failure Patients.
PMID- 27495794
TI - Copy number variations and cancer susceptibility: Retraction.
PMID- 27495793
TI - Prognostic Impact of Circulating Tumor Cell Detected Using a Novel Fluidic Cell
Microarray Chip System in Patients with Breast Cancer.
AB - Various types of circulating tumor cell (CTC) detection systems have recently
been developed that show a high CTC detection rate. However, it is a big
challenge to find a system that can provide better prognostic value than
CellSearch in head-to-head comparison. We have developed a novel semi-automated
CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures
CTC independently of tumor-specific markers or physical properties. Here, we
compared the CTC detection sensitivity and the prognostic value of FCMC with
CellSearch in breast cancer patients. FCMC was validated in preclinical studies
using spike-in samples and in blood samples from 20 healthy donors and 22 breast
cancer patients in this study. Using spike-in samples, a statistically higher
detection rate (p=0.010) of MDA-MB-231 cells and an equivalent detection rate
(p=0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch.
The number of CTC detected in samples from patients that was above a threshold
value as determined from healthy donors was evaluated. The CTC number detected
using FCMC was significantly higher than that using CellSearch (p=0.00037). CTC
numbers obtained using either FCMC or CellSearch had prognostic value, as
assessed by progression free survival. The hazard ratio between CTC+ and CTC- was
4.229 in CellSearch (95% CI, 1.31 to 13.66; p=0.01591); in contrast, it was 11.31
in FCMC (95% CI, 2.245 to 57.0; p=0.000244). CTC detected using FCMC, like the
CTC detected using CellSearch, have the potential to be a strong prognostic
factor for cancer patients.
PMID- 27495796
TI - Serum procalcitonin can guide antibiotic administration for respiratory tract
infections in primary care.
PMID- 27495797
TI - Sleep apnea is associated with an increased risk of mood disorders: a population
based cohort study.
AB - PURPOSE: The symptoms of sleep apnea, such as sleep fragmentation and oxygen
desaturation, might be risk factors for subsequent mood disorder (MD), but
associations between sleep apnea and MD remain unclear. This nationwide
population-based study thus aimed to identify the risk of MD in patients with vs.
without sleep apnea. METHODS: This cohort study used data from the National
Health Insurance database. In total, 5415 patients diagnosed with sleep apnea
between 2000 and 2010 were evaluated, and 27,075 matched non-sleep apnea
enrollees were included as a comparison cohort. All subjects were followed until
2011. The Cox proportional hazard ratio (HR) was used to investigate the
relationship between MD and sleep apnea while controlling covariates and
comorbidities of sleep apnea. RESULTS: Of 5415, 154 patients with sleep apnea
(2.84 %) were diagnosed with MD during the follow-up period in comparison with
306 of 27,075 individuals (1.13 %) without antecedent sleep apnea. After
adjusting for the selected factors and comorbidities, we found that patients with
sleep apnea were from 1.82- to 2.07-fold greater risk of MD than the comparisons.
Of the three subcategories of MD (major depressive disorder, bipolar disorder,
and unspecified MD), sleep apnea had the highest predisposing risk with respect
to major depressive disorder (adjusted HR from 1.82 to 2.07) and bipolar disorder
(adjusted HR from 2.15 to 3.24). CONCLUSIONS: There is a greater likelihood of MD
manifesting in patients with a history of sleep apnea. Health professionals are
thus advised to carefully monitor the psychological impacts of sleep apnea.
PMID- 27495799
TI - Another Form of Focal Choroidal Excavation Based on Multimodality Imaging.
AB - PURPOSE: To describe a peculiar choroidal entity using multimodality imaging and
to further understand the relationship between focal choroidal excavation and
central serous chorioretinopathy. CASE REPORT: A peculiar entity was detected in
both eyes of a 20-year-old male patient who was followed for more than 4 years;
one perifoveal focal choroidal excavation and two extrafoveal focal choroidal
excavations were noted in each eye. The bilateral perifoveal focal choroidal
excavations exhibited progressive development with repeated interconversion
between the nonconforming and conforming types. Dilated choroid blood vessels
were detected by en face spectral-domain optical coherence tomography (SD-OCT).
Although the ellipsoid zone and retinal pigment epithelium layer defect also
involved the fovea, a visual acuity of 20/20 was maintained in both eyes, with
neither metamorphopsia by Amsler grid nor abnormalities noted by multifocal
electroretinogram. However, pigment epithelium detachment finally appeared in the
right eye. The microperimetry test revealed reduced threshold sensitivity
corresponding to the lesions, and near-infrared autofluorescence revealed
increased hyperfluorescence at the latest visit. CONCLUSIONS: Idiopathic focal
choroidal excavation may convert to the structure of central serous
chorioretinopathy alike, which likely indicates another rare condition of focal
choroidal excavation or central serous chorioretinopathy. Wide- and deep-scanning
modes should be routinely applied in OCT imaging to detect choroidal disorders.
PMID- 27495800
TI - Low predictive value of sentinel lymph node biopsy in patients with thin
melanoma.
PMID- 27495798
TI - Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem
cell transplant recipients receiving levofloxacin prophylaxis in a Japanese
hospital.
AB - BACKGROUND: Breakthrough viridans streptococcal bacteremia (VSB) in patients with
hematological malignancy receiving levofloxacin prophylaxis is a major blood
stream infection (BSI) occurring during febrile neutropenia. However, clinical
data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT)
recipients are lacking. METHODS: The medical records of allo-HSCT recipients who
received oral levofloxacin prophylaxis between January 2011 and August 2013 at
Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans
streptococcal (VGS) species were identified by using sodA gene sequencing, and
were assessed for drug susceptibility. RESULTS: Among the 184 allo-HSCT
recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB.
All of the 28 recipients with VSB were treated with a cefepime-based or
piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS
strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and
vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50
(minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 MUg/mL and 2
MUg/mL, respectively) were higher than the MIC90 of all the other anti
pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC >= 2
MUg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress
syndrome (ARDS) that was associated with VSB, although the rate of viridans group
streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in
the VSB group (10.7 %) did not differ significantly from that in the BSI without
VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk
factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43).
CONCLUSIONS: APBL with increased anti-VGS activity (APBL-VA) monotherapy would
typically be optimal for treating the VGS strains in this setting. Indication of
adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should
depend on local factors, such as the susceptibility results. In addition,
breakthrough VSB is probably not a major cause of death in allo-HSCT settings,
where beta-lactam non-susceptible VGS and the ARDS are rare.
PMID- 27495801
TI - Pharmacological screening of Monotheca buxifolia (Falc.) A. DC. for
antinociceptive, anti-inflammatory and antipyretic activities.
AB - BACKGROUND: Medicinal plants have proven their importance as a valuable source of
molecules with therapeutic potential. Monotheca buxifolia (Falc.) A. DC. (family:
Sapotaceae) is traditionally used as a hematinic, laxative, digestive,
anthelmintic, antipyretic, and in the treatment of gastro-urinary disorders. To
provide scientific evidence for its folkloric use, the present study investigated
Monotheca buxifolia fruit hydro-ethanolic extract (MBHE) for its prospective
antinociceptive, anti-inflammatory and antipyretic activities. MBHE was eluted
through column chromatography to isolate the bioactive secondary metabolites
which may probably involve in its beneficial properties. METHODS: The
phytochemical constituents in MBHE was elucidated using UV, IR, (1)H-NMR, (13)C
NMR, 2D-NMR spectra in combination with EIMS and FAB-MS spectrometric techniques
and comparison with literature data of related compounds. The antinociceptive
activity of MBHE was evaluated in the acetic acid induced abdominal constriction
assay; the anti-inflammatory potential was assessed in the carrageenan induced
paw edema, while the antipyretic effect was tested against brewer's yeast induced
pyrexia in BALB/c mice at doses of 50, 100 and 150 mg/kg. RESULTS: Elution of
MBHE along with various characterization techniques led to the isolation of
oleanolic acid and isoquercetin. Significant attenuation of chemical induced
nociception was observed with MBHE at tested doses of 50 mg/kg (P < 0.01, 68.87
%), 100 mg/kg (P < 0.01, 68.87 %) and 150 mg/kg (P < 0.001, 83.02 %). During a
duration of 1-5 h in the carrageenan induced paw edema assay, significant
ameliorative effect (P < 0.01, P < 0.001) was demonstrated by MBHE at 50 mg/kg
(22.94-20 %), 100 mg/kg (33.23-21.13 %) and 150 mg/kg (38.23-25 %). MBHE also
significantly alleviated the brewer's yeast induced pyrexic response when tested
at doses of 50 mg/kg (P < 0.05 in 2nd h), 100 mg/kg (P < 0.05, P < 0.01 and P <
0.001 in 1-5 h) and 150 mg/kg (P < 0.01 and P < 0.001 in 1-5 h). CONCLUSION:
These findings suggest that Monotheca buxifolia possess pain, inflammation and
pyrexia ameliorating properties, probably mediated by the presence of oleanolic
acid and isoquercetin contents, though the involvement of other important
phytochemicals constituents cannot be ignored.
PMID- 27495802
TI - Food for thought? Potential conflicts of interest in academic experts advising
government and charities on dietary policies.
AB - BACKGROUND: A conflict of interest (CoI) can occur between public duty and
private interest, in which a public official's private-capacity interest could
improperly influence the performance of their official duties and
responsibilities. The most tangible and commonly considered CoI are financial.
However, CoI can also arise due to other types of influence including
interpersonal relationships, career progression, or ideology. CoI thus exist in
academia, business, government and non-governmental organisations. However,
public knowledge of CoI is currently limited due to a lack of information. The
mechanisms of managing potential conflicts of interest also remain unclear due to
a lack of guidelines. We therefore examined the independence of academic experts
and how well potential CoI are identified and addressed in four government and
non-governmental organisations in the UK responsible for the development of food
policy. METHODS: Policy analysis. We developed an analytical framework to explore
CoI in high-level UK food policy advice, using four case studies. Two government
policy-making bodies: Department of Health 'Obesity Review Group' (ORG),
'Scientific Advisory Committee on Nutrition' (SACN) and two charities: 'Action on
Sugar' (AoS), & 'Heart of Mersey' (HoM). Information was obtained from publicly
available sources and declarations. We developed a five point ordinal scale based
upon the ideology of the Nolan Principles of Public Life. Group members were
individually categorised on the ordinal ConScale from "0", (complete independence
from the food and drink industry) to "4", (employed by the food and drink
industry or a representative organisation). RESULTS: CoI involving various
industries have long been evident in policy making, academia and clinical
practice. Suggested approaches for managing CoI could be categorised as "deny",
"describe", or "diminish". Declared CoI were common in the ORG and SACN. 4 out of
28 ORG members were direct industry employees. In SACN 11 out of 17 members
declared industry advisory roles or industry research funding. The two charities
appeared to have equally strong academic expertise but fewer conflicts. No HoM
members declared CoI. 5 out of 21 AoS members declared links with industry,
mainly pharmaceutical companies. We were unable to obtain information on
conflicts for some individuals. CONCLUSIONS: Conflicts of interest are
unavoidable but potentially manageable. Government organisations responsible for
policy development and implementation must institutionalize an approach to
identify (disclose) and manage (mitigate or eliminate) perceived and actual CoI
to improve public confidence in government decision-making relevant to food
policy.
PMID- 27495803
TI - Assessment of the need for psychosomatic care in patients with suspected cardiac
disease.
AB - OBJECTIVE: The study aimed to assess the subjectively perceived need for
additional general disease-oriented and psychotherapeutic care in patients with
suspected cardiac disease and to investigate if the request for additional care
is consistent with impairment of generic quality of life and the presence of
psychosomatic risk factors. MATERIAL AND METHODS: Patients referred for cardiac
stress testing because of suspected cardiac disease completed the assessment of
the demand for additional psychological treatment (ADAPT) questionnaire, an
assessment tool for counselling demand in patients with chronic illness, the SF
36 quality of life and the hospital anxiety and depression scale (HADS)
questionnaires. RESULTS: The questionnaires were administered to 233 patients
(age: 54.5 +/- 13.4, 57.5 % male). Exclusive demand for disease-oriented
counselling was indicated by 45.1 %, demand for psychotherapeutic counselling
(exclusive or combined with disease-oriented demand) by 33.9 %. Almost all
patients with psychotherapeutic demand (96.3 %) expressed also request for
disease-oriented counselling. Patients with exclusive demand for disease-oriented
counselling showed significantly lower scores in the emotional and physical
functioning and role domains of the SF-36 than the norm population. Patients
demanding psychotherapeutic counselling reported significantly lower scores in
all SF-36 domains than the norm population. Psychotherapeutic demand was strongly
associated with positive indicators for mental distress: SF-36 MH (OR: 4.1), SF
36 MCS (OR: 5.9), HADS anxiety (OR: 3.9), and HADS depression (OR: 3.0).
CONCLUSIONS: Our study shows that the patients' request for additional care
reflects impairment of generic health status and psychological risk load. This
indicates that the assessment of subjectively perceived demand allows to screen
for patients who are in need of psychosomatic care and motivated to participate
in additional counselling and therapy.
PMID- 27495804
TI - Coronary fractional flow reserve measurements of a stenosed side branch: a
computational study investigating the influence of the bifurcation angle.
AB - BACKGROUND: Coronary hemodynamics and physiology specific for bifurcation lesions
was not well understood. To investigate the influence of the bifurcation angle on
the intracoronary hemodynamics of side branch (SB) lesions computational fluid
dynamics simulations were performed. METHODS: A parametric model representing a
left anterior descending-first diagonal coronary bifurcation lesion was created
according to the literature. Diameters obeyed fractal branching laws. Proximal
and distal main branch (DMB) stenoses were both set at 60 %. We varied the distal
bifurcation angles (40 degrees , 55 degrees , and 70 degrees ), the flow splits
to the DMB and SB (55 %:45 %, 65 %:35 %, and 75 %:25 %), and the SB stenoses (40,
60, and 80 %), resulting in 27 simulations. Fractional flow reserve, defined as
the ratio between the mean distal stenosis and mean aortic pressure during
maximal hyperemia, was calculated for the DMB and SB (FFRSB) for all simulations.
RESULTS: The largest differences in FFRSB comparing the largest and smallest
bifurcation angles were 0.02 (in cases with 40 % SB stenosis, irrespective of the
assumed flow split) and 0.05 (in cases with 60 % SB stenosis, flow split 55 %:45
%). When the SB stenosis was 80 %, the difference in FFRSB between the largest
and smallest bifurcation angle was 0.33 (flow split 55 %:45 %). By describing the
DeltaPSB-QSB relationship using a quadratic curve for cases with 80 % SB
stenosis, we found that the curve was steeper (i.e. higher flow resistance) when
bifurcation angle increases (DeltaP = 0.451*Q + 0.010*Q (2) and DeltaP = 0.687*Q
+ 0.017*Q (2) for 40 degrees and 70 degrees bifurcation angle, respectively).
Our analyses revealed complex hemodynamics in all cases with evident counter
rotating helical flow structures. Larger bifurcation angles resulted in more
pronounced helical flow structures (i.e. higher helicity intensity), when 60 or
80 % SB stenoses were present. A good correlation (R(2) = 0.80) between the SB
pressure drop and helicity intensity was also found. CONCLUSIONS: Our analyses
showed that, in bifurcation lesions with 60 % MB stenosis and 80 % SB stenosis,
SB pressure drop is higher for larger bifurcation angles suggesting higher flow
resistance (i.e. curves describing the DeltaPSB-QSB relationship being steeper).
When the SB stenosis is mild (40 %) or moderate (60 %), SB resistance is
minimally influenced by the bifurcation angle, with differences not being
clinically meaningful. Our findings also highlighted the complex interplay
between anatomy, pressure drops, and blood flow helicity in bifurcations.
PMID- 27495806
TI - David Oliver: NHS continuing care is a mess.
PMID- 27495805
TI - Effects of tDCS over the right DLPFC on attentional disengagement from positive
and negative faces: An eye-tracking study.
AB - The aim of this study was to increase insight in the neural substrates of
attention processes involved in emotion regulation. The effects of right
dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional
processing of emotional information were evaluated. A novel attention task
allowing a straightforward measurement of attentional engagement toward, and
attentional disengagement away from emotional faces was used. A sample of healthy
participants received 20 minutes of active and sham anodal transcranial direct
current stimulation (i.e., tDCS) applied over the right DLPFC on 2 separate days
and completed the attention task after receiving real or sham stimulation.
Compared to sham stimulation, tDCS over the right DLPFC led to impairments in
attentional disengagement from both positive and negative faces. Findings
demonstrate a causal role of right DLPFC activity in the generation of
attentional impairments that are implicated in emotional disturbances such as
depression and anxiety.
PMID- 27495807
TI - Spindle cell sarcomatoid carcinoma of the trachea: first case report of surgical
resection.
AB - BACKGROUND: Primary malignant tracheal tumors are rare, accounting for
approximately 0.2 % of respiratory tract tumors yearly, with squamous cell
carcinomas and adenoid cystic carcinomas accounting for two-thirds of these
cases. Sarcomatoid carcinomas are a group of poorly differentiated non-small cell
lung carcinomas containing a component of sarcoma or sarcoma-like (spindle and/or
giant cell) differentiation, categorized into five morphologic subgroups. Spindle
cell sarcomatoid carcinoma is a rare variant of sarcomatoid carcinomas,
consisting of only spindle-shaped tumor cells. Only one other case has been
reported as a primary tracheal tumor. CASE PRESENTATION: We present a 75-year-old
male, having progressive dyspnea and cough, with a spindle cell sarcomatoid
carcinoma tumor visualized on chest computed tomography scan and confirmed with
biopsy. CONCLUSIONS: Due to its low incidence, knowledge of treatment methods,
prognostic factors, and etiology is limited thus approaches to eradication have
widely varied. We are reporting the second published case of spindle cell
sarcomatoid carcinoma of the trachea and the first reported successful outcome of
definitive treatment with tracheal resection.
PMID- 27495808
TI - Population-level effects of abamectin, azadirachtin and fenpyroximate on the
predatory mite Neoseiulus baraki.
AB - The coconut production system, in which the coconut mite Aceria guerreronis is
considered a key pest, provides an interesting model for integration of
biological and chemical control. In Brazil, the most promising biological control
agent for the coconut mite is the phytoseiid predator Neoseiulus baraki. However,
acaricides are widely used to control the coconut mite, although they frequently
produce unsatisfactory results. In this study, we evaluated the simultaneous
direct effect of dry residue contact and contaminated prey ingestion of the main
acaricides used on coconut palms (i.e., abamectin, azadirachtin and
fenpyroximate) on life-history traits of N. baraki and their offspring. These
acaricides are registered, recommended and widely used against A. guerreronis in
Brazil, and they were tested at their label rates. The offspring of the exposed
predators was also evaluated by estimating the instantaneous rate of population
increase (r i ). Abamectin compromised female performance, whereas fenpyroximate
did not affect the exposed females (F0). Nonetheless, fenpyroximate strongly
compromised the offspring (F1) net reproductive rate (R0), intrinsic rate of
population growth (r i ), and doubling time (DT). In contrast, fenpyroximate did
not have such effects on the 2nd generation (F2) of predators with acaricide
exposed grandparents. Azadirachtin did not affect the predators, suggesting that
this acaricide can be used in association with biological control by this
predatory species. In contrast, the use of abamectin and fenpyroximate is likely
to lead to adverse consequences in the biological control of A. guerreronis using
N. baraki.
PMID- 27495809
TI - Does Surgeon Experience Impact the Risk of Complications After Bernese
Periacetabular Osteotomy?
AB - BACKGROUND: Bernese periacetabular osteotomy (PAO) is a technically challenging
procedure with potential risk for major complications and a previously reported
steep learning curve. However, the impact of contemporary hip preservation
fellowships on the learning curve of PAO has not been established.
QUESTIONS/PURPOSES: (1) What was the frequency of major complications during the
PAO learning curve of two surgeons who recently graduated from hip preservation
fellowships? (2) Is increasing level of experience associated with the risk of a
complication and with operative time, a possible surrogate measure of surgical
performance? METHODS: We retrospectively studied 81 PAOs performed by one of two
surgeons who recently graduated from a hip preservation fellowship during their
first 4 years of practice in two institutions. One of the surgeons participated
as a fellow in 78 PAOs with an increasing level of responsibility during the
course of 1 full year. The other surgeon performed 41 PAOs as a fellow during 6
months, also with an increasing level of responsibility during that time. There
were 68 (84%) female and 13 (16%) male patients (mean age, 18 years; range, 10-36
years). The frequency of complications was recorded early and at 1 year after
surgery and graded according to a validated classification system describing five
grades of complications. Complications that required surgical intervention (Grade
III) and life-threatening complications (Grade IV) were considered major
complications. Persistent pain after surgery, although considered a failure of
PAO, was not considered a surgical complication as a result of the multifactorial
etiology of pain after hip-preserving surgery. However, early reoperation and
revision surgery were counted as complications. To evaluate the association
between increasing level of experience and the occurrence of complications, we
divided each surgeon's experience into his first 20 procedures (initial interval)
and his second 20 (experienced interval) to test whether the incidence of
complications or operative time was different between the two intervals. Because
the association between experience and the likelihood of a complication was
estimated to be consistent between the two surgeons, the analysis was performed
with data pooled from the two surgeons. To test whether there was a difference in
the likelihood of a complication in the initial and the experienced intervals, a
multivariate logistic regression analysis was performed and the adjusted risk of
a complication between the two intervals was calculated. Linear regression
analyses were used to test the association between surgeon level of experience
and operative time. RESULTS: The overall incidence of major (Grade III or Grade
IV) complications was 6% (95% confidence interval [CI], 2%-14%). These included
deep infection (3% [three of 81]), intraoperative posterior column fracture (1%
[one of 81]), and pulmonary embolism (1% [one of 81]). With the numbers
available, the risk of a complication did not decrease with increasing surgeon
experience. After controlling for body mass index and surgeon, the frequency of a
complication did not decrease in the experienced interval relative to the initial
interval (odds ratio, 0.78; 95% CI, 0.25-2.4; p = 0.6623). The adjusted risk
difference between the experienced interval relative and the initial interval was
6% (95% CI, -11% to 23%). When experience was modeled as a continuous variable
(number of PAOs performed), increasing experience was not associated with a lower
likelihood of a complication (odds ratio per one PAO increase in experience,
0.99; 95% CI, 0.94-1.04; p = 0.5478). However, after adjusting for body mass
index and surgeon, increased experience was associated with a reduction in
operative time (slope [change in log operative time per one procedure increase in
experience], -0.005; 95% CI, -0.009 to -0.0005; p = 0.0292). For every one
additional PAO increase in experience, there was a 0.45% decrease in operative
time (95% CI, 0.05%-0.86% decrease]. CONCLUSIONS: With a case exposure greater
than 40 PAOs and progressive surgical responsibility during contemporary
structured training, two young surgeons were able to perform PAO with a low risk
of complications. However, even with that surgical experience before independent
practice, surgical time decreased over the first 40 PAOs they performed
independently. Our data may help guide orthopaedic residency and hip preservation
fellowship programs in establishing training requirements and assessing
competency in PAO. LEVEL OF EVIDENCE: Level III, therapeutic study.
PMID- 27495810
TI - Syndromic anorectal malformation associated with Holt-Oram syndrome,
microcephaly, and bilateral corneal opacity: a case report.
AB - BACKGROUND: The occurrence of an anorectal malformation with Holt-Oram syndrome,
microcephaly, and bilateral corneal opacity is rare and to the best of our
knowledge has not previously been reported in the literature. Hence, there is a
need to document our experience in this case and learn as much as possible from
it. CASE PRESENTATION: We present the case of a Nigerian female neonate with a
postnatal diagnosis of syndromic anorectal malformation associated with Holt-Oram
syndrome, microcephaly, and bilateral corneal opacity. The infant had successful
staged correction of her anorectal malformation but developed a metastatic Wilms'
tumor and died before other corrective procedures could be instituted.
CONCLUSIONS: An anorectal malformation is here reported to occur with Holt-Oram
syndrome, an association that has not been reported previously. To enhance the
prognosis and quality of life of children with syndromic anorectal malformation,
prenatal ultrasound monitoring of high-risk pregnancies and expertise in prenatal
detection of congenital anomalies are invaluable in antenatal care.
PMID- 27495811
TI - The Arabidopsis hnRNP-Q Protein LIF2 and the PRC1 Subunit LHP1 Function in
Concert to Regulate the Transcription of Stress-Responsive Genes.
AB - LHP1-INTERACTING FACTOR2 (LIF2), a heterogeneous nuclear ribonucleoprotein
involved in Arabidopsis thaliana cell fate and stress responses, interacts with
LIKE HETEROCHROMATIN PROTEIN1 (LHP1), a Polycomb Repressive Complex1 subunit. To
investigate LIF2-LHP1 functional interplay, we mapped their genome-wide
distributions in wild-type, lif2, and lhp1 backgrounds, under standard and stress
conditions. Interestingly, LHP1-targeted regions form local clusters, suggesting
an underlying functional organization of the plant genome. Regions targeted by
both LIF2 and LHP1 were enriched in stress-responsive genes, the H2A.Z histone
variant, and antagonistic histone marks. We identified specific motifs within the
targeted regions, including a G-box-like motif, a GAGA motif, and a telo-box.
LIF2 and LHP1 can operate both antagonistically and synergistically. In response
to methyl jasmonate treatment, LIF2 was rapidly recruited to chromatin, where it
mediated transcriptional gene activation. Thus, LIF2 and LHP1 participate in
transcriptional switches in stress-response pathways.
PMID- 27495813
TI - Understanding patterns and factors associated with place of death in patients
with end-stage kidney disease: A retrospective cohort study.
AB - BACKGROUND: Meeting place-of-death preferences is an important measure of the
quality of end-of-life care. Systematic review shows that 42% of end-stage kidney
disease patients prefer home death. Little research has been undertaken on place
of death. AIM: To understand patterns of place of death in patients with end
stage kidney disease known in one UK renal unit. DESIGN: A retrospective cohort
study of all patients with chronic kidney disease stage 4-5, age ?75 and known to
one UK renal unit, who died between 2006 and 2012. Patients were categorised into
three management pathways: haemodialysis, conservative and pre-dialysis. RESULTS:
A total of 321 patients (mean age, 82.7; standard deviation, 5.21) died (61.7%
male). In all, 62.9% died in hospital (95% confidence interval, 57.5%-68.1%),
21.8% died in their usual place of residence (95% confidence interval, 17.5%
26.6%) and 15.3% died in an inpatient palliative care unit (95% confidence
interval, 11.6%-19.5%). Management pathway and living circumstances were most
strongly associated with place of death. Patients on the conservative pathway had
four times the odds of dying out of hospital (odds ratio, 4.0; 95% confidence
interval, 2.1-7.5; p < 0.01). Patients living alone were less likely to die out
of hospital (odds ratio, 0.3; 95% confidence interval, 0.1-0.6; p < 0.01). There
were also changes in place of death over time, with more patients dying out of
hospital in 2012 compared to 2006 (odds ratio, 3.1; 95% confidence interval, 1.0
9.7; p < 0.05). CONCLUSION: Most patients with end-stage kidney disease die in
hospital, but patients managed without dialysis are significantly more likely to
die outside of hospital. Planning ahead is key to be able to meet preference for
place of death.
PMID- 27495812
TI - FYVE1/FREE1 Interacts with the PYL4 ABA Receptor and Mediates Its Delivery to the
Vacuolar Degradation Pathway.
AB - Recently, we described the ubiquitylation of PYL4 and PYR1 by the RING E3
ubiquitin ligase RSL1 at the plasma membrane of Arabidopsis thaliana This
suggested that ubiquitylated abscisic acid (ABA) receptors might be targeted to
the vacuolar degradation pathway because such ubiquitylation is usually an
internalization signal for the endocytic route. Here, we show that FYVE1
(previously termed FREE1), a recently described component of the endosomal
sorting complex required for transport (ESCRT) machinery, interacted with RSL1
receptor complexes and recruited PYL4 to endosomal compartments. Although the
ESCRT pathway has been assumed to be reserved for integral membrane proteins, we
show the involvement of this pathway in the degradation of ABA receptors, which
can be associated with membranes but are not integral membrane proteins.
Knockdown fyve1 alleles are hypersensitive to ABA, illustrating the biological
relevance of the ESCRT pathway for the modulation of ABA signaling. In addition,
fyve1 mutants are impaired in the targeting of ABA receptors for vacuolar
degradation, leading to increased accumulation of PYL4 and an enhanced response
to ABA Pharmacological and genetic approaches revealed a dynamic turnover of ABA
receptors from the plasma membrane to the endosomal/vacuolar degradation pathway,
which was mediated by FYVE1 and was dependent on RSL1. This process involves
clathrin-mediated endocytosis and trafficking of PYL4 through the ESCRT pathway,
which helps to regulate the turnover of ABA receptors and attenuate ABA
signaling.
PMID- 27495814
TI - Experiences of patients and caregivers with early palliative care: A qualitative
study.
AB - BACKGROUND: Early palliative care improves quality of life and satisfaction with
care and is increasingly endorsed for patients with advanced cancer. However,
little is known about the experience of receiving early palliative care from a
patient and caregiver perspective. AIM: The aim of this qualitative study was to
determine, from a participant perspective, the experience of receiving early
palliative care and elements of that care. DESIGN: Qualitative grounded theory
study using individual interviews. SETTING/PARTICIPANTS: The study took place at
a comprehensive cancer centre. Patients ( n = 26) and caregivers ( n = 14) from
the intervention arm of a cluster-randomised controlled trial of early palliative
care versus standard oncology care participated in qualitative interviews.
Participants were asked to comment on their quality of life, the quality of care
provided over the intervention period and their experiences with the palliative
care team. RESULTS: Participants described feeling supported and guided in their
illness experience and in their navigation of the healthcare system. Specific
elements of early palliative care included prompt, personalised symptom
management; holistic support for patients and caregivers; guidance in decision
making; and preparation for the future. Patients with symptoms particularly
valued prompt attention to their physical concerns, while those without symptoms
valued other elements of care. Although three patients were ambivalent about
their current need for palliative care, no distress was reported as a consequence
of the intervention. CONCLUSION: The elements of care described by participants
may be used to develop, support and refine models of early palliative care for
patients with cancer.
PMID- 27495815
TI - Survival is associated with complete response on MRI after neoadjuvant
chemotherapy in ER-positive HER2-negative breast cancer.
AB - BACKGROUND: Pathological complete remission (pCR) of estrogen receptor (ER)
positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer
is rarely achieved after neoadjuvant chemotherapy (NAC). In addition, the
prognostic value of pCR for this breast cancer subtype is limited. We explored
whether response evaluation by magnetic resonance imaging (MRI) is associated
with recurrence-free survival after NAC in ER-positive/HER2-negative breast
cancer. METHODS: MRI examinations were performed in 272 women with ER
positive/HER2-negative breast cancer before, during and after NAC. MRI
interpretation included lesion morphology at baseline, changes in morphology and
size, and contrast uptake kinetics. These MRI features, clinical characteristics
and final pathology were correlated with recurrence-free survival. RESULTS: The
median follow up time was 41 months. There were 35 women with events, including
19 breast-cancer-related deaths. On multivariable analysis, age younger than 50
years (hazard ratio (HR) = 2.55, 95 % confidence interval (CI) 1.3, 5.02, p =
0.007), radiological complete response after NAC (HR = 14.11, CI 1.81, 1818; p =
0.006) and smaller diameters of washout/plateau enhancement at MRI after NAC (HR
= 1.02, CI 1.00, 1.04, p = 0.036) were independently associated with best
recurrence-free survival. Pathological response was not significant; HR = 2.12,
CI 0.86, 4.64, p = 0.096. CONCLUSIONS: MRI after NAC in ER-positive/HER2-negative
tumors may be predictive of recurrence-free survival. A radiological complete
response at MRI after NAC is associated with an excellent prognosis.
PMID- 27495816
TI - Functional Neurologic Outcomes Change Over the First 6 Months After Cardiac
Arrest.
AB - OBJECTIVES: To determine the longitudinal changes in functional outcome and
compare ordinal outcome scale assessments in comatose cardiac arrest survivors.
DESIGN: Prospective observational study of comatose cardiac arrest survivors.
Subjects who survived to 1 month were included. SETTING: Academic medical center
ICU. PATIENTS: Ninety-eight consecutive patients who remained comatose after
resuscitation from cardiac arrest; 45 patients survived to 1 month.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients' functional
neurologic outcomes were assessed by phone call or in-person clinic visit at 1,
3, 6, and 12 months postcardiac arrest using the modified Rankin Scale, Glasgow
Outcome Scale, and Barthel Index. A "good" outcome was defined as modified Rankin
Scale 0-3, Barthel Index 70-100, and Glasgow Outcome Scale 4-5. Changes in
dichotomized outcomes and shifts on each outcome scale were analyzed. The mean
age of survivors was 51 +/- 19 years and 18 (40%) were women. Five (19%) out of
26 patients with data available at all timepoints improved to good modified
Rankin Scale outcome and none worsened to poor outcome between postarrest months
1 and 6 (p = 0.06). Thirteen patients (50%) improved on the modified Rankin Scale
by 1-3 points and four (15%) worsened by 1-2 points between months 1 and 6
(overall improvement by 0.5 points; 95% CI, 0-1; p = 0.04). From postarrest
months 6 to 12, there was no change in the number of patients with good versus
poor outcomes. The modified Rankin Scale and Barthel Index were more sensitive to
detecting changes in outcome than the Glasgow Outcome Scale. CONCLUSIONS: In
initially comatose cardiac arrest survivors, improvements in functional status
occur over the first 6 months after the event. There was no significant change in
outcome between postarrest months 6 and 12. The modified Rankin Scale is a
sensitive outcome scale in this population.
PMID- 27495817
TI - Academic Productivity of Accreditation Council for Graduate Medical Education
Accredited Critical Care Fellowship Program Directors.
AB - OBJECTIVES: Academic productivity is an expectation for program directors of
Accreditation Council for Graduate Medical Education-accredited subspecialty
programs in critical care medicine. Within the adult critical care Accreditation
Council for Graduate Medical Education-accredited programs, we hypothesized that
program director length of time from subspecialty critical care certification
would correlate positively with academic productivity, and primary field would
impact academic productivity. DESIGN: This study received Institutional Review
Board exemption from the University of Florida. Data were obtained from public
websites on program directors from all institutions that had surgery,
anesthesiology, and pulmonary Accreditation Council for Graduate Medical
Education-accredited subspecialty critical care training programs during calendar
year 2012. Information gathered included year of board certification and
appointment to program director, academic rank, National Institutes of Health
funding history, and PubMed citations. RESULTS: Specialty area was significantly
associated with total (all types of publications) (p = 0.0002), recent (p <
0.0001), last author (p = 0.008), and original research publications (p <
0.0001), even after accounting for academic rank, years certified, and as a
program director. These differences were most prominent in full professors, with
surgery full professors having more total, recent, last author, and original
research publications than full professors in the other critical care
specialties. CONCLUSIONS: This study demonstrates that one's specialty area in
critical care is an independent predictor of academic productivity, with surgery
having the highest productivity. For some metrics, such as total and last author
publications, surgery had more publications than both anesthesiology and
pulmonary, whereas there was no difference between the latter groups. This
suggests that observed differences in academic productivity vary by specialty.
PMID- 27495818
TI - Prognostic Impact of Persistent Thrombocytopenia During Extracorporeal Membrane
Oxygenation: A Retrospective Analysis of Prospectively Collected Data From a
Cohort of Patients With Left Ventricular Dysfunction After Cardiac Surgery.
AB - OBJECTIVE: The prognostic impact of thrombocytopenia in patients supported by
extracorporeal membrane oxygenation after cardiac surgery is uncertain. We
investigated whether thrombocytopenia is independently predictive of poor outcome
and describe the incidence and time course of thrombocytopenia in extracorporeal
membrane oxygenation patients. DESIGN: Retrospective analysis of prospectively
collected data. SETTING: Cardiosurgical ICU at a tertiary referral center.
PATIENTS: Three hundred adult patients supported with venoarterial extracorporeal
membrane oxygenation for more than 24 hours because of refractory cardiogenic
shock after heart surgery between January 2001 and December 2014. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Two-way analysis of variance was used to
compare the time course of platelet count changes between survivors and
nonsurvivors. Using multiple Cox regression with time-dependent covariates, we
investigated the impact of platelet count on 90-day mortality. In nonsurvivors,
the daily incidence of moderate (< 100 - 50 * 10/L), severe (49 - 20 * 10/L), and
very severe (< 20 * 10/L) thrombocytopenia was 50%, 54%, and 7%, respectively.
Platelet count had a biphasic temporal pattern with an initial decrease until day
4-5 after the initiation of extracorporeal membrane oxygenation. Although a
significant recovery of the platelet count was observed in survivors, a recovery
did not occur in nonsurvivors (p = 0.0001). After adjusting for suspected
confounders, moderate, severe, and very severe thrombocytopenia were
independently associated with 90-day mortality. The highest risk was associated
with severe (hazard ratio, 5.9 [2.7-12.6]; p < 0.0001) and very severe
thrombocytopenia (hazard ratio, 25.9 [10.7-62.9], p < 0.0001). CONCLUSION:
Thrombocytopenia is an independent risk factor for poor outcome in extracorporeal
membrane oxygenation patients after cardiac surgery, with persistent severe
thrombocytopenia likely reflecting a high degree of physiologic imbalance.
PMID- 27495819
TI - Visual Fixation in the ICU: A Strong Predictor of Long-Term Recovery After
Moderate-to-Severe Traumatic Brain Injury.
AB - OBJECTIVE: Posttraumatic amnesia is superior to the initial Glasgow Coma Scale
score for predicting traumatic brain injury recovery, but it takes days/weeks to
assess. Here, we examined whether return of visual fixation-a potential marker of
higher cognitive function-within 24 hours of ICU admission could be used as an
early predictor of traumatic brain injury recovery. DESIGN: Two-phase cohort
study. SETTING: Level-I trauma ICU. PATIENTS: Moderate-to-severe traumatic brain
injury discharged alive between 2010 and 2013. INTERVENTIONS: None. MEASUREMENTS
AND MAIN RESULTS: Return of visual fixation was assessed through standard
behavioral assessments in 181 traumatic brain injury patients who had lost the
ability to fixate at ICU admission (phase 1) and compared with posttraumatic
amnesia duration and the initial Glasgow Coma Scale score to predict performance
on the Glasgow Outcome Scale-Extended 10-40 months after injury (n = 144; phase
2a). A subgroup also completed a visual attention task (n = 35; phase 2b) and a
brain MRI after traumatic brain injury (n = 23; phase 2c). With an area under the
curve equal to 0.85, presence/absence of visual fixation at 24 hours of ICU
admission was found as performant as posttraumatic amnesia (area under the curve,
0.81; difference between area under the curve, 0.04; p = 0.28) for predicting
patients' Glasgow Outcome Scale-Extended score. Conversely, the initial Glasgow
Coma Scale score was not (area under the curve, 0.63). Even when controlling for
age/medication/CT scan findings, fixation remained a significant predictor of
Glasgow Outcome Scale-Extended scores (beta, -0.29; p < 0.05). Poorer attention
performances and greater regional brain volume deficits were also observed in
patients who could not fixate at 24 hours of ICU admission versus those who
could. CONCLUSIONS: Visual fixation within 24 hours of ICU admission could be as
performant as posttraumatic amnesia for predicting traumatic brain injury
recovery, introducing a new variable of interest in traumatic brain injury
outcome research.
PMID- 27495820
TI - Lactated Ringer Is Associated With Reduced Mortality and Less Acute Kidney Injury
in Critically Ill Patients: A Retrospective Cohort Analysis.
AB - OBJECTIVES: To assess the impact of the percentage of fluid infused as Lactated
Ringer (%LR) during the first 2 days of ICU admission in hospital mortality and
occurrence of acute kidney injury. DESIGN: Retrospective cohort. SETTING:
Analysis of a large public database (Multiparameter Intelligent Monitoring in
Intensive Care-II). PATIENTS: Adult patients with at least 2 days of ICU stay,
admission creatinine lower than 5 mg/dL, and that received at least 500 mL of
fluid in the first 48 hours. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS:
10,249 patients were included in mortality analysis and 8,085 were included in
the acute kidney injury analysis. For acute kidney injury analysis, we excluded
patients achieving acute kidney injury criteria in the first 2 days of ICU stay.
Acute kidney injury was defined as stage 2/3 Kidney Disease: Improving Global
Outcomes creatinine criteria and was assessed from days 3-7. The effects of %LR
in both outcomes were assessed through logistic regression controlling for
confounders. Principal component analysis was applied to assess the effect of
volume of each fluid type on mortality. Higher %LR was associated with lower
mortality and less acute kidney injury. %LR effect increased with total volume of
fluid infused. For patients in the fourth quartile of fluid volume (> 7 L), the
odds ratio for mortality for %LR equal to 75% versus %LR equal to 25% was 0.50
(95% CI, 0.32-0.79; p < 0.001). Principal component analysis suggested that
volume of Lactated Ringer and 0.9% saline infused had opposite effects in
outcome, favoring Lactated Ringer. CONCLUSIONS: Higher %LR was associated with
reduced hospital mortality and with less acute kidney injury from days 3-7 after
ICU admission. The association between %LR and mortality was influenced by the
total volume of fluids infused.
PMID- 27495821
TI - The Role of kappa Opioid Receptor in Brain Ischemia.
AB - OBJECTIVES: Our previous studies indicated that highly selective kappa opioid
receptor agonists could protect the brain, indicating an important role of kappa
opioid receptor agonist in brain ischemia. In this study, we investigated the
role and related mechanisms of kappa opioid receptor agonists in brain ischemia
in a middle cerebral artery occlusion mouse model. DESIGN: Animal model. SETTING:
Laboratory. SUBJECTS: The middle cerebral artery occlusion model was established
by 120 minutes of ischemia followed by 24-hour reperfusion in male adult mice.
INTERVENTIONS: Various doses of salvinorin A, a highly selective and potent kappa
opioid receptor agonist, were administered intranasally 10 minutes after
initiation of reperfusion. Norbinaltorphimine (2.5 mg/kg, IP) as a kappa opioid
receptor antagonist was administered in one group before administration of
salvinorin A (50MUg/kg) to investigate the specific role of kappa opioid
receptor. MEASUREMENTS AND MAIN RESULTS: Infarct volume, kappa opioid receptor
expression, and Evans blue extravasation in the brain, and neurobehavioral
outcome were determined. Immunohistochemistry and western blot were performed to
detect the activated caspase-3, interleukin-10, and tumor necrosis factor-alpha
levels to investigate the role of apoptosis and inflammation. kappa opioid
receptor expression was elevated significantly in the ischemic penumbral area
compared with that in the nonischemic area. Salvinorin A reduced infarct volume
and improved neurologic deficits dose-dependently. Salvinorin A at the dose of 50
MUg/kg reduced Evans blue extravasation, suggesting reduced impairment of the
blood-brain barrier and decreased the expression of cleaved caspase-3,
interleukin-10, and tumor necrosis factor-alpha in the penumbral areas. All these
changes were blocked or alleviated by norbinaltorphimine. CONCLUSIONS: kappa
opioid receptors were up-regulated and played a critical role in brain ischemia
and reperfusion. kappa opioid receptor activation could potentially protect the
brain and improve neurologic outcome via blood-brain barrier protection,
apoptosis reduction, and inflammation inhibition.
PMID- 27495822
TI - Visual system for communicating quality of evidence and strength of
recommendations.
PMID- 27495823
TI - Prospective cohort study of pregnant Brazilian women elucidates link between Zika
virus infection and fetal abnormalities.
PMID- 27495824
TI - Sedation during bronchoscopy: data from a nationwide sedation and monitoring
survey.
AB - BACKGROUND: There is limited knowledge on practice patterns in procedural
sedation and analgesia (PSA), the use of propofol, and monitoring during flexible
bronchoscopy (FB). The purpose of this study was to assess the current practice
patterns of FBs and to focus on the use of propofol, the education of the
proceduralist, and the involvement of anaesthesiologists during FB. METHODS: An
anonymous questionnaire was sent to 299 pulmonologists. Only respondents who were
active physicians in adult respiratory medicine performing FB were subsequently
analysed. RESULTS: The response rate was 78 % and 27,149 FB in the previous 12
months were analysed. The overall sedation-related morbidity rate was 0.02 % and
mortality was 7/100'000 FB. Sedation was used in 95 % of bronchoscopies. The main
drugs used for PSA were propofol (77 %) and midazolam (46 %). In 84 % of PSAs
propofol was used without the attendance of an anaesthesiologist. The use of
propofol was associated with high volume bronchoscopists (p < 0.010) and career
young pulmonologists (p < 0.001). While monitoring vital parameters has become
standard practice, pulmonologists reported a very low rate of systematic basic
education and training in the field of PSA (50 %). CONCLUSIONS: In Switzerland,
PSA during FB is mostly performed with propofol without the attendance of an
anaesthesiologist and the use of this drug is expected to increase in the future.
While monitoring standards are very high there is need for policies to improve
education, systematic training, and support for pulmonologists for PSA during FB.
PMID- 27495825
TI - RIFM fragrance ingredient safety assessment, Isopulegol, CAS Registry Number 89
79-2.
AB - This material was evaluated for genotoxicity, repeated dose toxicity,
developmental and reproductive toxicity, local respiratory toxicity,
phototoxicity/photoallergenicity, skin sensitization, as well as environmental
safety. Data show that this material is not genotoxic nor does it have skin
sensitization potential. The repeated dose, developmental and reproductive, and
local respiratory toxicity endpoints were completed using the TTC (Threshold of
Toxicological Concern) for a Cramer Class I material (0.03, 0.03 mg/kg/day and
1.4 mg/day, respectively). The phototoxicity/photoallergenicity endpoint was
completed based on suitable UV spectra. The environmental endpoint was completed
as described in the RIFM Framework.
PMID- 27495826
TI - In vitro toxicity of reuterin, a potential food biopreservative.
AB - Reuterin has a high potential as a food preservative due to both its chemical
characteristics and its antimicrobial activity against food-borne pathogens and
spoilage bacteria. However, there is a lack of information about its toxicity and
its capacity to interfere with the metabolism of drugs by inhibiting cytochrome
P450 (CYP) activity. The results of this study indicated that reuterin exhibited
a moderate cytotoxicity in the human hepatoma cell line HepG2 according to assays
measuring three different endpoints in the same set of cells. Reuterin was much
less toxic than acrolein and only four times more toxic than diacetyl, a
generally recognized as safe flavoring compound. In vitro experiments utilizing
human liver microsomes showed that reuterin presents low possibility of
displaying in vivo drug interactions by inhibition of CYP3A4, CYP2D6, and CYP2C9.
Therefore, reuterin can be considered a promising food biopreservative, although
additional toxicology research is needed before permission for use can be
granted.
PMID- 27495827
TI - Parsing polyphyletic Pueraria: Delimiting distinct evolutionary lineages through
phylogeny.
AB - Several taxonomic and phylogenetic studies have hypothesized polyphyly within
Pueraria DC., a genus comprising 19 species (24 with varieties) including the
highly invasive Pueraria montana var. lobata (Kudzu) introduced to the U.S.A.
about 150years ago. Previous efforts to investigate monophyly of the genus have
been hampered by limited taxon sampling or a lack of comprehensive evolutionary
context that would enable definitive taxonomic associations. This work presents a
comprehensive phylogenetic investigation of Pueraria within the context of tribe
Phaseoleae (Leguminosae). Polyphyly was found to be more extensive than
previously thought, with five distinct lineages spread across the tribe and
spanning over 25mya of divergence strongly supported by two chloroplast and one
nuclear marker, AS2, presented here as a phylogenetic marker for the first time.
Our phylogenies support taxonomic revisions to rectify polyphyly within Pueraria,
including the resurrection of Neustanthus, moving one species to Teyleria, and
the creation of two new genera, Haymondia and Toxicopueraria (taxonomic revisions
published elsewhere).
PMID- 27495828
TI - Subjective sleep measures for adolescents: a systematic review.
AB - BACKGROUND: Sleep disturbances in adolescents have received significant attention
because of their high prevalence and the negative health outcomes. Relative to
objective measures, subjective sleep instruments have been the most practical
tools used to identify sleep problems and assess responses to interventions in
research and clinical settings. This systematic review aims to examine the
psychometric properties of subjective measures that are used to assess sleep
quality and disturbances among adolescents, identify the strength and limitation
of each measurement and inform recommendations for practice. METHODS: PubMed,
Embase and PsycInfo were searched from 2000 through May 2016. The reference lists
of important articles were included if they met the inclusion criteria. The
available measures were evaluated and classified as positive, intermediate or
poor according to the quality criteria for health status questionnaires. RESULTS:
Thirteen self-reported or parent-reported sleep measures met the inclusion
criteria. Of the measurements reviewed, six were generic instruments assessing
overall sleep quality and disturbances; five were dimension-specific instruments
measuring daytime sleepiness, sleep insufficiency and sleep hygiene; and two were
condition-specific instruments for insomnia. None of the subjective sleep
measures for adolescents has a psychometric profile with all essential
measurement properties. Specifically, the generic sleep measurements capture
multiple dimensions but face issues of participant burden and compatibility.
Among the domain-specific tools, the Cleveland Adolescent Sleepiness
Questionnaire and the Chronic Sleep Reduction Questionnaire have achieved good
psychometric merits but need further evaluation for responsiveness. Likewise,
essential measurement properties of condition-specific tools for insomnia have
yet to be established. CONCLUSIONS: Because of the limited evidence, no definite
recommendations can be made at this point. However, each available measurement
has its own uniqueness and strength despite the limitations. Future research on
measurement development and evaluation for adolescent sleep is needed to ensure
the relevance and suitability to different stages of adolescence and social
contexts.
PMID- 27495829
TI - Atherosclerotic Surrogate Markers in Adults With Down Syndrome: A Case-Control
Study.
AB - The authors aimed to compare surrogate markers of atherosclerosis (pulse wave
velocity, intima-media thickness) between adults with and without Down syndrome
(DS) and to assess the impact of parathyroid hormone levels and classic
cardiovascular risk factors on arterial stiffness. After comparing 51 adults with
DS and 51 healthy adults (siblings of DS individuals), the authors found that
adults with DS seem to have lower arterial stiffness, as a result of chronic
hypotension. Subclinical atherosclerosis parameters do not correlate with
traditional cardiovascular risk factors in adults with DS, thus raising the
hypothesis that classic predictive models for cardiovascular disease are not
valid in this population. Hyperparathyroidism could play an important role in
arterial damage in these individuals. The lower than expected prevalence of
obesity and dyslipidemia could be explained by better eating habits, with this
study being the first to address the anthropometric and clinical profile of a
Mediterranean cohort of adults with DS.
PMID- 27495830
TI - [Direct service costs of diabetes mellitus hospitalisations in the Mexican
Institute of Social Security].
AB - OBJECTIVE: To estimate the direct costs related to hospitalizations for diabetes
mellitus and its complications in the Mexican Institute of Social Security
METHODS: The hospital care costs of patients with diabetes mellitus using
diagnosis-related groups in the IMSS (Mexican Institute of Social Security) and
the hospital discharges from the corresponding E10-E14 codes for diabetes
mellitus were estimated between 2008-2013. Costs were grouped according to
demographic characteristics and main condition, and were estimated in US dollars
in 2013. RESULTS: 411,302 diabetes mellitus discharges were recorded,
representing a cost of $1,563 million. 52.44% of hospital discharges were men and
77.26% were for type 2 diabetes mellitus. The biggest cost was attributed to
peripheral circulatory complications (34.84%) and people from 45-64 years of age
(47.1%). Discharges decreased by 3.84% and total costs by 1.75% in the period
analysed. The complications that caused the biggest cost variations were
ketoacidosis (50.7%), ophthalmic (22.6%) and circulatory (18.81%). CONCLUSIONS:
Hospital care for diabetes mellitus represents an important financial challenge
for the IMSS. The increase in the frequency of hospitalisations in the productive
age group, which affects society as a whole, is an even bigger challenge, and
suggests the need to strengthen monitoring of diabetics in order to prevent
complications that require hospital care.
PMID- 27495831
TI - Predictors of Occult Atrial Fibrillation in One Hundred Seventy-One Patients with
Cryptogenic Transient Ischemic Attack and Minor Stroke.
AB - BACKGROUND AND OBJECTIVE: Recent randomized studies have shown the potential of
prolonged cardiac rhythm monitoring to detect silent paroxysmal atrial
fibrillation (PAF) in patients with cryptogenic stroke. Our aim was to identify
clinical and magnetic resonance imaging (MRI) factors that predict the detection
of PAF during long-duration rhythm cardiac Holter (LDRCH) monitoring. METHODS: A
retrospective analysis was performed using data from 171 patients with
cryptogenic stroke or transient ischemic attack who underwent LDRCH monitoring
(i.e., 21 days) from 2009 to 2013. Clinical, echocardiographic, and imaging
predictors of atrial fibrillation (AF) were determined by multivariable analysis.
RESULTS: PAF lasting more than or equal to 30 seconds was diagnosed in 26 of 171
(15%) patients. Median delay to first detected AF episode was 7 (interquartile
range: 2-13) days. Four factors were independently predictive of PAF detection on
LDRCH: age more than 70 years (odds ratio [OR], 4.6; 95% confidence interval
[CI], 1.5-13.8); premature atrial complex on electrocardiogram (OR, 4.6; 95% CI,
1.1-19.6); left ventricular hypertrophy on transthoracic echocardiography (OR,
6.4, 95% CI, 1.6-26.4); and previous white matter lesions on brain MRI (OR, 4.2;
95% CI, 1.2-15.6). Recent brain infarction pattern on diffusion-weighted imaging
was not associated with PAF detection on LDRCH. CONCLUSION: LDRCH is a
noninvasive and inexpensive test with a high rate of AF detection in patients
with cryptogenic stroke or transient ischemic attack. Occult PAF was more
commonly diagnosed in older patients with premature atrial complex on the
baseline electrocardiogram, left ventricular hypertrophy on echocardiography, and
with previous white matter lesions on brain MRI.
PMID- 27495832
TI - COA-Cl, a Novel Synthesized Nucleoside Analog, Exerts Neuroprotective Effects in
the Acute Phase of Intracerebral Hemorrhage.
AB - BACKGROUND: A previous study in our laboratory showed the neuroprotective effects
of COA-Cl, a novel synthesized adenosine analog, in a rat cerebral ischemia
model. The purpose of the present study was to evaluate the neuroprotective
effects of COA-Cl in intracerebral hemorrhage (ICH), another common type of
stroke, and investigate potential mechanisms of action. METHODS: Adult Sprague
Dawley rats received an injection of 100 ul autologous whole blood into the right
basal ganglia. COA-Cl (30 ug/kg) was injected intracerebroventricularly 10
minutes after ICH. A battery of motor deficit tests were performed at 1 day, 3
days, 5 days, and 7 days after ICH. To investigate the mechanism of action, brain
water content, TUNEL staining and 8-OHdG immunostaining, and ELISA (to assess
oxidative stress) were used. RESULTS: COA-Cl treatment significantly attenuated
sensorimotor deficits and reduced brain edema 1 day after ICH. Furthermore, the
numbers of perihematomal TUNEL- and 8-OHdG-positive cells were significantly
decreased in COA-Cl treated ICH rats. CONCLUSIONS: These results indicate that
COA-Cl has neuroprotective effects in ICH. Furthermore, our study provides
evidence that COA-Cl may reduce oxidative stress, which may be one mechanism
underlying its neuroprotective effects.
PMID- 27495833
TI - Intravenous Thrombolysis and Passes of Thrombectomy as Predictors for
Endovascular Revascularization in Ischemic Stroke.
AB - BACKGROUND: Patient selection for endovascular revascularization treatment (ERT)
in acute ischemic stroke depends on the expected benefit-risk ratio. As rapid
revascularization is a major determinant of good functional outcome, we aimed to
identify its predictors after ERT. METHODS: Consecutive stroke patients from a
single stroke center with distal internal carotid artery-, proximal middle
cerebral artery- or T-occlusions treated with ERT were retrospectively selected.
We assessed admission noncontrast computed tomography and computed tomography
angiography for thrombus location, thrombus load (clot burden score), and
collateral status. Clinical data were extracted from medical charts. Univariate
and multivariate regression analyses were performed to identify predictors of
revascularization (thrombolysis in cerebral infarction >=2b) after ERT. RESULTS:
A total of 63 patients were identified (median age, 73 years; interquartile
range: 62-77; 40 females). Sixteen patients (25.4%) underwent intravenous
thrombolysis (ivT) before ERT. Twenty-two patients (34.9%) had additional intra
arterial application of recombinant tissue plasminogen activator. The overall
recanalization rate was 66.7%, and 9.5% had symptomatic intracranial bleeding. In
hospital mortality was 15%, and 30% reached good functional outcome at discharge.
In the univariate analysis, preceding ivT and the number of passes for
thrombectomy (dichotomized <=2 versus >2) were associated with recanalization.
There was a trend for number of thrombectomy passes (as continuous variable) and
multimodal ERT. In the multivariate regression analysis, ivT prior to ERT and
passes of thrombectomy were identified as independent predictors for
recanalization. CONCLUSION: ivT and lower passes of thrombectomy are associated
with recanalization after ERT for ischemic stroke with proximal vessel
occlusions.
PMID- 27495834
TI - How Commonly Is Stroke Found in Patients with Isolated Vertigo or Dizziness
Attack?
AB - BACKGROUND: The sudden development of vertigo or dizziness without focal
neurological symptoms is generally attributable to vestibular diseases such as
benign paroxysmal positional vertigo. Isolated vertigo or dizziness attack needs
more attention than vestibular diseases. This retrospective study was performed
to elucidate the frequency of strokes in patients with isolated vertigo or
dizziness attack. SUBJECTS AND METHODS: We enrolled 221 patients (men, 119;
women, 102; mean age, 68.4 +/- 10.3 years) who were admitted to our hospital over
the last 10 years because of sudden isolated vertigo or dizziness attack without
other neurological symptoms except for nystagmus, deafness, or tinnitus. We
investigated the clinical features, final diagnosis, neuroimaging findings, and
short- or long-term outcome of these patients. RESULTS: One hundred eighteen
patients had vertigo whereas the other 103 had dizziness. Brain computed
tomography or magnetic resonance imaging revealed recent stroke lesions in 25
patients (11.3%) (ischemic, 21; hemorrhagic, 4).The lesions were generally small
and localized in the cerebellum (n = 21), pons (n = 1), medulla oblongata (n =
1), or corona radiata (n = 1). Of the 25 patients, 19 (76%) had dizzy-type
spells; none had neurological dysfunction at the time of discharge. In the
remaining 196 patients, no stroke was detected on computed tomography or magnetic
resonance imaging. CONCLUSIONS: Stroke was found in 11% of patients with isolated
vertigo or dizziness attack. The posterior inferior cerebellar artery area was
the most frequently implicated for isolated vertigo or dizziness.
PMID- 27495835
TI - Anticancer activity of gallic acid template-based benzylidene indanone derivative
as microtubule destabilizer.
AB - Benzylidene indanones have been designed and synthesized from gallic acid, a
plant phenolic acid as possible anticancer agent. The best analogue of the
series, that is, 3-(3',4',5'-trimethoxyphenyl)-4,5,6-trimethoxy-2-(4"
nitrobenzylidene)-indan-1-one (8) exhibited potent cytotoxicity (IC50 =3-10 MUm)
against several human cancer cell lines through microtubule destabilization (IC50
=1.54 MUm) after occupying colchicine-binding site of beta-tubulin. In cell cycle
analysis, compound 8 exerted G2/M phase arrest in both MCF-7 and MDA-MB-231 cells
and induced apoptosis. It reduced 34.8% solid tumor in in vivo Ehrlich ascite
carcinoma in Swiss albino mice at 30 mg/kg dose. In acute oral toxicity
experiment, it was tolerable up to 300 mg/kg doses in Swiss albino mice. The lead
compound 8 needs to be optimized for better activity.
PMID- 27495836
TI - A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells.
AB - BACKGROUND: Radioresistant glioblastoma stem cells (GSCs) contribute to tumor
recurrence and identification of the molecular targets involved in
radioresistance mechanisms is likely to enhance therapeutic efficacy. This study
analyzed the DNA damage response following ionizing radiation (IR) in 10 GSC
lines derived from patients. METHODS: DNA damage was quantified by Comet assay
and DNA repair effectors were assessed by Low Density Array. The effect of RAD51
inhibitor, RI-1, was evaluated by comet and annexin V assays. RESULTS: While all
GSC lines displayed efficient DNA repair machinery following ionizing radiation,
our results demonstrated heterogeneous responses within two distinct groups
showing different intrinsic radioresistance, up to 4Gy for group 1 and up to 8Gy
for group 2. Radioresistant cell group 2 (comprising 5 out of 10 GSCs) showed
significantly higher RAD51 expression after IR. In these cells, inhibition of
RAD51 prevented DNA repair up to 180 min after IR and induced apoptosis. In
addition, RAD51 protein expression in glioblastoma seems to be associated with
poor progression-free survival. CONCLUSION: These results underscore the
importance of RAD51 in radioresistance of GSCs. RAD51 inhibition could be a
therapeutic strategy helping to treat a significant number of glioblastoma, in
combination with radiotherapy.
PMID- 27495837
TI - Gender Differences in Mobility Device Use Among U.S. Older Adults.
AB - Objectives: Research has shown greater mobility limitations among women than men.
We aimed to examine (a) gender differences in the use of canes for mobility and
(b) what factors contribute to these differences under the frameworks of the
disablement model and the Theory of Planned Behavior. Method: Using National
Health and Aging Trends Study data, we estimated hierarchical logistic regression
models to predict the likelihood of cane use among older adults who completed
performance-based measures (n = 5,503). We tested the interactions between gender
and selected variables to further understand gender difference. Results: In
unadjusted analysis, 22% of women and 16% of men used canes. In models adjusted
in steps for sociodemographics, health, physical impairments, capacity,
psychosocial, and social environment factors, women were progressively less
likely to use canes, significantly so at the last step. Suppression effect
analyses showed the influence of living alone and receiving mobility help
variables. Interaction analyses showed that women reporting poor health or
balance were less likely to use canes; obese women were more likely. Discussion:
Significant gender differences exist in cane use among older community-living
adults. Findings suggest that health and function partly account for these
differences. Future research is needed to understand social/cultural factors
involved.
PMID- 27495838
TI - Rapid detection of G6PD mutations by multicolor melting curve analysis.
AB - The MeltPro G6PD assay is the first commercial genetic test for glucose-6
phosphate dehydrogenase (G6PD) deficiency. This multicolor melting curve analysis
based real-time PCR assay is designed to genotype 16 G6PD mutations prevalent in
the Chinese population. We comprehensively evaluated both the analytical and
clinical performances of this assay. All 16 mutations were accurately genotyped,
and the standard deviation of the measured Tm was <0.3 degrees C. The limit of
detection was 1.0ng/MUL human genomic DNA. The assay could be run on four
mainstream models of real-time PCR machines. The shortest running time (150min)
was obtained with LightCycler 480 II. A clinical study using 763 samples
collected from three hospitals indicated that, of 433 samples with reduced G6PD
activity, the MeltPro assay identified 423 samples as mutant, yielding a clinical
sensitivity of 97.7% (423/433). Of the 117 male samples with normal G6PD
activity, the MeltPro assay confirmed that 116 samples were wild type, yielding a
clinical specificity of 99.1% (116/117). Moreover, the MeltPro assay demonstrated
100% concordance with DNA sequencing for all targeted mutations. We concluded
that the MeltPro G6PD assay is useful as a diagnostic or screening tool for G6PD
deficiency in clinical settings.
PMID- 27495839
TI - Practical methods for collecting Trichinella parasites and their excretory
secretory products.
AB - Trichinella is a unique nematode. Its developmental stages include adult worms,
newborn larvae, and muscle larvae. Besides humans, the parasite also infects many
kinds of animals, including mice. Mice are widely used as an animal model in the
research fields of immunology, cell biology, and host-parasite relationships of
trichinellosis. The different developmental stages of Trichinella share similar,
but unique characteristics. Therefore, it is important to collect different
sources of Trichinella-derived materials for research with appropriate methods.
In the present study, we introduce methods to collect Trichinella at different
stages as well as their ES products. By optimizing the concentration of
artificial gastric juice, volume of medium, and time of incubation for ES
collection in vitro, muscle larvae, adult worms, and newborn larvae were
collected with less contamination by host materials, and the ES products
collected were confirmed to be originally antigenic and biologically active. The
DNA, RNA, and proteins isolated from the parasites collected were confirmed to be
applicable to analyses, including PCR, real-time PCR, Western blotting, and
stimulators of cell cultures (macrophages, splenocytes, and tumor cells). The
present study compiled protocols to collect materials from Trichinella and
provides a reference for research on Trichinella.
PMID- 27495840
TI - When Does Hearing Loss Occur in Vestibular Schwannoma Surgery? Importance of
Auditory Brainstem Response Changes in Early Postoperative Phase.
AB - OBJECTIVE: Some patients suffer postoperative hearing loss even when the
intraoperative auditory brainstem response (ABR) is preserved during vestibular
schwannomas surgery. This study was conducted to evaluate whether there are
dynamic changes of the ABR after surgery. PATIENTS AND METHODS: In a prospective
study from 2010-2012, 46 patients (24 female and 22 male) with vestibular
schwannomas were investigated by intraoperative and postoperative ABR monitoring.
Development of ABR quality during and after surgery (Class 1 normal, Class 5
complete loss) was correlated to auditory outcome. RESULTS: At the end of
surgery, 17 patients had an ABR Class 1-4 and 29 had Class 5. Four hours after
surgery, 9 of 23 (39%) patients showed an ABR quality change, and 24 hours after
surgery, 15 of 30 (50%) had undergone ABR quality changes. Four different types
of postoperative ABR courses could be distinguished-Course 1: stable with
reproducible ABR, Course 2: unstable with reproducible ABR, Course 3: unstable
with ABR loss, and Course 4: stable with ABR loss. These courses correlated
highly significantly with the intraoperative development (P < 0.001) and with
hearing outcome (P = 0.003). CONCLUSION: The study identifies ongoing changes of
ABR quality and hearing function after the end of vestibular schwannoma surgery.
Therefore it seems worthwhile to continue ABR monitoring in the postoperative
phase in order to identify patients who are at risk of a secondary hearing
deterioration and start therapeutic interventions in a timely manner.
PMID- 27495841
TI - Complications in Endovascular Neurosurgery: Critical Analysis and Classification.
AB - BACKGROUND: Precisely defining complications, which are used to measure overall
quality, is necessary for critical review of delivery of care and quality
improvement in endovascular neurosurgery, which lacks common definitions for
complications. Furthermore, in endovascular interventions, events that may be
labeled complications may not always negatively affect outcome. Our objective is
to provide precise definitions for quality evaluation within endovascular
neurosurgery. Thus, we propose an endovascular-specific classification system of
complications based on our own patient series. METHODS: This single-center review
included all patients who had endovascular interventions from September 2013 to
August 2015. Complication types were analyzed, and a descriptive analysis was
undertaken to calculate the incidence of complications overall and in each
category. RESULTS: Two hundred and seventy-five endovascular interventions were
performed in 245 patients (65% female; mean age, 55 years). Forty complications
occurred in 39 patients (15%), most commonly during treatment of intracranial
aneurysms (24/40). Mechanical complications (eg, device deployment, catheter, or
closure device failure) occurred in 8/40, technical complications (eg, failure to
deploy flow diverter, unintended embolization, air emboli, retroperitoneal
hemorrhage, dissection) in 11/40, judgment errors (eg, patient or equipment
selection) in 9/40, and critical events (eg, groin hematoma, hemorrhagic or
thromboembolic complications) in 12/40 patients. Only 12/40 complications (30%)
resulted in new neurologic deficits, vessel injury requiring surgery, or blood
transfusion. CONCLUSIONS: We propose an endovascular-specific classification
system of complications with 4 categories: mechanical, technical, judgment
errors, and critical events. This system provides a framework for future studies
and quality control in endovascular neurosurgery.
PMID- 27495842
TI - Full-Endoscopic Transforaminal Approach for Removal of a Spontaneous Spinal
Epidural Hematoma.
AB - BACKGROUND: The incidence of spinal epidural hematoma (SEH) is estimated to be 1
per 1,000,000 patients per year; SEH can be classified as idiopathic,
spontaneous, and secondary. The cause of spontaneous SEH is uncertain but it may
be associated with minor trauma. SEH can compress surrounding structures, shown
by clinical symptoms and signs that affect the spinal cord or nerve roots.
Surgical treatment may be considered if medical treatment fails. CASE
DESCRIPTION: A 26-year-old man presented with lower back pain and significant
radicular symptoms on the left side for a week. He denied previous lumbar trauma
or the use of anticoagulation drugs. We used the full-endoscopic transforaminal
approach (extraforaminal technique) to remove the SEH under local anesthesia. The
patient was discharged home 2 days after surgery and the radicular pain
disappeared completely. Three months later, follow-up magnetic resonance imaging
showed that the dark-brown lesion had been totally removed. CONCLUSIONS:
Spontaneous SEHs are uncommon. Although lumbar laminectomy is the mainstream
treatment in those with neurologic deficits caused by epidural hematomas, the
percutaneous full-endoscopic transforaminal approach may be an option for certain
SEHs.
PMID- 27495843
TI - Indirect Bypass Surgery May Be More Beneficial for Symptomatic Patients with
Moyamoya Disease at Early Suzuki Stage.
AB - OBJECTIVE: Moyamoya disease is a progressive stenosis or occlusion of the
internal carotid artery. Revascularization surgery is considered the standard
treatment. We conducted a retrospective study in hopes of finding indications for
electing different surgical methods. METHODS: A total of 55 hemispheres in 49
patients who received revascularization surgery between January 2013 and December
2015 were included. Medical data such as age and sex were extracted and risk
factor analysis for vascular anastomosis patency was conducted with multivariable
logistic regression. RESULTS: In this study, direct or combined bypass surgery
had a higher incidence of perioperative neurologic defects than did indirect
surgery (30.3% vs. 4.5%; P = 0.046). The rates of postsurgery stroke (6.2% vs.
18.2%) and modified Rankin Scale improvement (39.4% vs. 18.2%) were better in the
direct or combined bypass surgery group, but no significant difference was found.
Moreover, longer operative time (209 +/- 29.4 minutes vs. 101 +/- 16.5 minutes; P
< 0.01) and longer hospital stay (9.0 +/- 3.11 days vs. 5.3 +/- 2.03 days; P <
0.01) made direct or combined bypass surgery less advantageous. Multivariable
binary logistic regression showed that the late Suzuki stage is a more favorable
factor than the early Suzuki stage (odd ratio, 7.78; confidence interval, 1.059
57.155; P = 0.044). CONCLUSIONS: Because vascular anastomosis patency in
symptomatic patients with moyamoya disease at early Suzuki stage is relatively
lower, indirect bypass surgery may be more beneficial for these patients in view
of shorter operative time and hospital stay.
PMID- 27495844
TI - Epidemiologic and Demographic Attributes of Primary Spondylodiscitis in a Middle
Eastern Population Sample.
AB - BACKGROUND: The prevalence and characteristics of spontaneous spondylodiscitis in
the Middle East are unknown. There seems to be an emerging dominance of pyogenic
infections over tuberculosis and brucellosis. METHODS: We conducted a
retrospective observational study based on electronic case records of 4 years
from a tertiary reference facility in Oman. Case records, microbiology reports,
blood reports, imaging studies, and histopathology, and surgical reports of all
spinal infection cases were studied. Patients with secondary infections after
invasive spinal interventions and expatriate patients were excluded. Risk factors
and comorbidities were also analyzed. RESULTS: Sixty-two cases of primary
spondylodiscitis of the spine were identified in this cohort, including 10 cases
of tuberculosis, 1 of brucellosis, and 1 of tuberculosis with pyogenic infection.
Of the 50 pyogenic infections, 4 were in children; among the adults, the mean age
was 49.5 years and 63.8% were male. Thirty-three patients had no medical
comorbidities. Common ailments associated were 18 patients with diabetes
mellitus, 13 hypertensives, 6 with renal insufficiency, 2 with liver cirrhosis, 3
with alcoholism, 5 with hepatitis C virus, and 2 with immunosuppression. More
than 69% involvement was in the lumbar spine. Fourteen patients were infected
with Staphylococcus aureus and 9 with Pseudomonas aeruginosa, whereas 35.4% were
culture negative. CONCLUSIONS: Spontaneous infective spondylodiscitis affects
older men with and without medical comorbidities equally. It often involves the
lumbar spine and a third of patients are culture negative. Tuberculosis
constitutes only about 17% of primary infections in the spine in this population
sample.
PMID- 27495845
TI - Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for
Germ Cell Tumours.
AB - BACKGROUND: Clinical management of germ cell tumours (GCTs) relies on monitoring
of serum tumour markers. However, the markers alpha-fetoprotein (AFP), the beta
subunit of human chorionic gonadotropin (bHCG), and lactate dehydrogenase (LDH)
are expressed in <60% of GCT cases. OBJECTIVE: To test the utility of the
microRNAs (miRNAs) miR-371a-3p, miR-372-3p, miR-373-3p, and miR-367-3p as
sensitive and specific GCT serum biomarkers. DESIGN, SETTING, AND PARTICIPANTS:
Serum levels of miRNAs were measured in 166 consecutive patients with GCT before
and after treatment and in 106 male controls. In the first 50 consecutive
patients, all four miRNAs were measured. In the main study, only the most
sensitive miRNA was further analysed. OUTCOME MEASUREMENTS AND STATISTICAL
ANALYSIS: The specificity and sensitivity of the four miRNAs were studied using
receiver operating characteristic curves. miRNA sensitivities were compared to
those of classical markers. Statistical cross-comparisons of miRNA levels for GCT
subgroups and controls were performed at various time points during treatment.
RESULTS AND LIMITATIONS: Overall, miR-371a-3p performed best, with 88.7%
sensitivity (95% confidence interval [CI] 82.5-93.3%) and 93.4% specificity (95%
CI 86.9-97.3%) and an area under the curve of 0.94, outperforming AFP, bHCG, and
LDH (combined sensitivity 50%). According to Kernel density estimation, the
sensitivity and specificity were 86.3% and 92.5%, respectively. miR-371a-3p
levels dropped to normal after completion of treatment. The miRNA levels
correlated with treatment failure and relapse. Teratoma did not express miR-371a
3p. CONCLUSIONS: The miRNA miR-371a-3p is a specific and sensitive novel serum
GCT biomarker that accurately correlates with disease activity. Validation of
this test in a large-scale prospective study is needed. PATIENT SUMMARY: miR-371a
3p is a novel serum marker for germ cell tumours that is expressed by 88.7% of
patients and thus is far more sensitive and specific than classical serum
markers. It correlates with tumour burden and treatment results. Validation in a
large patient cohort is needed.
PMID- 27495846
TI - Re: More Favorable Pathological Outcomes in Men with Low Risk Prostate Cancer
Diagnosed on Repeat Versus Initial Transrectal Ultrasound Guided Prostate Biopsy.
PMID- 27495847
TI - Re: Re-evaluating PSA Testing Rates in the PLCO Trial.
PMID- 27495849
TI - Abdominal rectus diastasis: Questions of wellness and biology.
PMID- 27495848
TI - Bile deficiency induces changes in intestinal glucose absorption in mice.
AB - BACKGROUND: Biliary tract obstruction is a common clinical problem. In this
study, we attempted to understand the change in intestinal glucose absorption
after biliary tract obstruction. METHODS: Experimental models of murine biliary
duct ligation and external biliary drainage were established. Murine intestinal
mucosal glucose absorption was examined with Ussing chambers according to the
increase in the short-circuit current in vitro and blood glucose measurement
after oral glucose in vivo. The protein expression of the sodium-glucose
cotransporter (SGLT1) and the facilitated glucose transporter, member 2 (GLUT2)
was analyzed by Western blot and immunohistochemistry. RESULTS: The results from
Ussing chamber experiments showed that duodenal mucosal glucose absorption levels
were significantly higher in biliary duct ligation and biliary drainage mice than
those in normal control mice at 1 and 2 weeks after the operation.
Gastrointestinal bile acid administration almost reversed the elevated duodenal
mucosal glucose absorption to the normal level in biliary drainage mice. The
results from the experiments in vivo further confirmed that the glucose
absorption increased in biliary duct ligation and biliary drainage mice. The
protein expression levels of SGLT1 in the duodenal mucosae of both biliary duct
ligation and biliary drainage mice were markedly higher than those in control
mice, and the protein expression of GLUT2 was not significantly altered, compared
with control mice. CONCLUSION: Bile deficiency in the intestine upregulates the
expression of intestinal mucosal SGLT1 and enhances intestinal mucosal glucose
absorption capacity, which contributes to the understanding of intestinal
physiologic function for patients with biliary duct obstruction and external
biliary drainage.
PMID- 27495850
TI - Predictors of improved survival for patients with retroperitoneal sarcoma.
AB - BACKGROUND: Retroperitoneal sarcomas are rare tumors that can be locally
aggressive with high rates of recurrence. Given that data on survival in patients
with retroperitoneal sarcomas are conflicting, we sought to use a nationwide
cancer database to identify factors associated with survival in patients with
retroperitoneal sarcomas. METHODS: The Surveillance, Epidemiology, and End
Results database was utilized to identify patients with retroperitoneal sarcomas
from 2002 to 2012. Univariable and multivariable survival analysis was performed
using a generalized gamma parametric survival function. RESULTS: A total of 2,920
patients were included; overall 5- and 10-year survivals were 58.4% and 45.3%,
respectively. On multivariable survival analysis, age, histologic type, grade,
size, local extension, lymph node, and distant metastasis were associated with
decreased survival (all P < .05). Patients undergoing operative resection
survived 2.5 times longer (95% confidence interval: 2.0-3.0, P < .001) and those
receiving radiation therapy 1.3 times longer (95% confidence interval: 1.1-1.6, P
= .001), respectively. CONCLUSION: During the past decade, retroperitoneal
sarcoma patients treated with radiation demonstrate longer survival compared with
patients who did not receive radiation. Further study is needed to fully
elucidate the mechanisms that underlie the radiation-related survival benefit
observed in this study.
PMID- 27495851
TI - Mapping insulin non-covalent interactions with natural polysaccharides by
hydrogen/deuterium exchange mass spectrometry.
AB - RATIONALE: Drug development efforts involving therapeutic peptides or proteins
strongly lead optimization of drug delivery, drug stability, solubility and
functionality. The key feature of controlled drug delivery is the use of
biocompatible polymers able to interact via non-covalent bonds with an active
principle through multiple functional groups. Here amide hydrogen/deuterium
exchange (HDX) mass spectrometry was employed to localize insulin dynamics
induced by interactions with three natural polysaccharides, i.e. chitosan (CH),
sodium alginate (ALG) and chondroitin sulfate (CS). METHODS: LTQ-Orbitap
continuous-labelling mass spectra were collected by diluting insulin stock
solution (10 mM in 0.1% formic acid) to a final concentration of 0.1 mM in D2 O
containing 1 mM deuterated ammonium acetate (final pH .6) (insulin:polysaccharide
ratio 1:2, w/w). For peptide mapping, deuterated samples were quenched after 0.5,
30, 60, 120 minutes exchange by adding HCl (pH ) and digested with pepsin before
LC-MS/MS analysis. RESULTS: Differences in the insulin backbone dynamics in the
presence of the three polysaccharides were highlighted by monitoring peptic
peptides at different time points. No significant differences were observed in
the presence of CH, whereas the negatively charged ALG and CS were able to induce
significant conformational variations at the B-chain level resulting in more
protection against H/D exchange. The A-chain interacted only with CS reducing the
protein mobility on a long time scale (120 min). HDX data evidenced heterogeneous
insulin dynamics in the presence of ALG and CS. CONCLUSIONS: The studies reported
here demonstrated the capabilities of mass spectrometry techniques and HDX
methods to obtain useful information toward the flexibility and the behavior of
native insulin in the presence of natural polysaccharides, and could provide
insights to study the behavior of pharmaceutical formulations. Copyright (c) 2016
John Wiley & Sons, Ltd.
PMID- 27495852
TI - Arthroscopy Authors Seek Innovative International Readers.
AB - Arthroscopy and Arthroscopy Techniques attract authors as a result of our large,
innovative, and global audience. In addition, the journals attract authors
because of our robust and rapid review process, our wide indexing and search
availability, and our openness to diverse article types including Technical Notes
with video.
PMID- 27495853
TI - Mark P. Cote, P.T., D.P.T., M.S.C.T.R., Associate Editor.
PMID- 27495854
TI - Authors' Reply.
PMID- 27495855
TI - Regarding "Autologous Osteochondral Transplantation for Osteochondral Lesions of
the Talus: Does Previous Bone Marrow Stimulation Negatively Affect Clinical
Outcome?".
PMID- 27495856
TI - Authors' Reply.
PMID- 27495857
TI - Regarding "Use of Hip Arthroscopy and Risk of Conversion to Total Hip
Arthroplasty: A Population-Based Analysis".
PMID- 27495858
TI - Editorial Commentary: Call for Evidence: How and When to Treat a Stiff Shoulder
in Diabetics Requires Clarification.
AB - The present study found a slower functional recovery after arthroscopic capsular
release in patients with refractory frozen shoulder and diabetes. However, the
study has some limitations: retrospective design, small study groups, and
incomplete assessments. To better understand the disease and its proper
treatment, one has to distinguish between idiopathic and secondary frozen
shoulder. At present, little is known about both types of frozen shoulder, and
randomized controlled trials are needed to compare surgical intervention with a
conservative treatment at different stages of the disease.
PMID- 27495859
TI - Editorial Commentary: Your Surgical "Tool Box" Just Got a Little Bit Bigger.
AB - There is currently no "gold standard" for the surgical repair of a partial
thickness rotator cuff tear. Ranalletta et al. have made a meaningful
contribution to the orthopaedic literature with this study that reports the
clinical outcomes of 80 patients who underwent arthroscopic transtendon repair of
high-grade, articular-sided partial-thickness rotator cuff tears. At a mean
follow-up of 62 months, they noted significant improvement in pain, range of
motion, and a number of objective shoulder outcome measures. Perhaps most
importantly, 92.5% rated their shoulder as "good" or "excellent." Unfortunately,
we cannot definitively state whether or not these repairs actually healed given
the lack of postoperative imaging, nor do we know the actual depth of these
partial tears that can be difficult to objectively quantify. Despite these
shortcomings, arthroscopic surgeons who treat rotator cuff disorders will be able
to use this information in treating their patients irrespective of their
preferred surgical technique. Future studies are needed to definitively determine
which repair method, if any, is better.
PMID- 27495860
TI - Editorial Commentary: Low Reoperation Rates for Outpatient Rotator Cuff Repairs:
Proof of Efficacy?
AB - The reoperation rate for people younger than 65 years is approximately 8% at a
minimum 2-year follow-up. The low rate is another indicator that outpatient
rotator cuff repair is a good operation with acceptable failure risks.
PMID- 27495861
TI - Editorial Commentary: Are Larger Screws the Answer When Anatomic Reconstruction
of an Acromioclavicular Separation Fails?
AB - Although fixation methods have improved, failure after fixation of an
acromioclavicular joint separation is not uncommon. This biomechanical study
shows that in the setting of graft slippage through previously well-placed
clavicular tunnels, a revision anatomic reconstruction is feasible with larger
tenodesis screws. Although the risk of clavicular fracture increases with larger
tunnels, anatomic revision with larger screws is an option in select cases.
PMID- 27495862
TI - Editorial Commentary: Pitching Should Come With a Warning Label.
AB - Pitching is not without risk of overuse injuries. Pitch counts have been
instituted to reduce the risk, but Riff et al.'s article clearly demonstrates
that as pitchers get older they do not adhere to these counts, which increases
the risk of injury.
PMID- 27495863
TI - Editorial Commentary: Risk Factors for Chondral Lesions in the Hip-There Is More
to It Than Cam and Pincer.
AB - Age has been cited in a recent article as the largest predictor of both chondral
and labral lesions in patients with hip dysplasia. But it was not surprising that
there is also a direct relation between a small lateral center-edge angle,
acetabular head index, and cartilage degeneration and an increased acetabular
index and labral tears in patients with hip dysplasia. The severity of the
congenital disease determines the severity of the intra-articular lesions.
PMID- 27495865
TI - Editorial Commentary: Outcomes After Patch Use in Rotator Cuff Surgery: Searching
for the "Holy Grail".
AB - Rotator cuff integrity after repair is the basis for a better patient outcome,
and the use of adjunctive graft material may result in a demonstrable benefit
toward achieving that end.
PMID- 27495864
TI - Editorial Commentary: Postoperative Anterior Cruciate Ligament Reconstruction
Protocols Are Like Snowflakes; No 2 Are Alike.
AB - Postoperative rehabilitation after arthroscopic and related surgery should follow
guidelines that emphasize time (tissue healing) and performance (motion and
strength) milestones. These guidelines are often missing in traditional
protocols, which assume that all patients arrive in the same condition at the
same point in time. The real challenge for the allied health professional will be
demonstrating that milestone-based protocols that use the best available evidence
are effective, and as a start, we need to eliminate treatments proven
ineffective.
PMID- 27495866
TI - Editorial Commentary: Love My Surgeon, Love My Surgery: Patient Satisfaction
Matters After Hip Arthroscopy.
AB - Patient satisfaction following hip arthroscopy is currently underreported and
lacks uniformity when published. While current patient reported outcomes are
important, they may not reflect overall patient satisfaction because it is
complex and multifactorial. However, assessment and documentation of patient
satisfaction following hip arthroscopy is critical to demonstrating value and
quality. Therefore, it is of pressing importance that the hip arthroscopy
community develops an accurate score that is consistent, valid, and reliable.
PMID- 27495868
TI - Erratum.
PMID- 27495867
TI - Editorial Commentary: The Importance of Developing an Algorithm When Diagnosing
Hip Pain.
AB - The differential diagnosis of groin pain is broad and complex. Therefore, it is
essential to develop an algorithm when differentiating the hip as a cause of
groin pain from other sources. Selective injections in and around the hip can be
helpful when making the diagnosis but are only one part of the algorithm.
PMID- 27495869
TI - Phase 3 evaluation of HP802-247 in the treatment of chronic venous leg ulcers.
AB - In 2012 we reported promising results from a phase 2 clinical trial of HP802-247,
a novel spray-applied investigational treatment for chronic venous leg ulcers
consisting of human, allogeneic fibroblasts and keratinocytes. We now describe
phase 3 clinical testing of HP802-247, its failure to detect efficacy, and
subsequent investigation into the root causes of the failure. Two randomized,
controlled trials enrolled a total of 673 adult outpatients at 96 centers in
North America and Europe. The primary endpoint was the proportion of ulcers with
confirmed closure at the end of 12 weeks of treatment. An investigation into the
root cause for the failure of HP802-247 to show efficacy in these two phase 3
trials was initiated immediately following the initial review of the North
American trial results. Four hundred twenty-one patients were enrolled in the
North American (HP802-247, 211; Vehicle 210) and 252 in the European (HP802-247,
131; Vehicle 121) trials. No difference in proportion of closed ulcers at week 12
was observed between treatment groups for either the North American (HP802-247,
61.1%; Vehicle 60.0%; p = 0.5896) or the European (HP802-247, 47.0%; Vehicle
50.0%; p = 0.5348) trials. Thorough investigation found no likelihood that design
or execution of the trials contributed to the failure. Variability over time
during the trials in the clinical response implicated the quality of the cells
comprising HP802-247. Concordance between the two separate, randomized,
controlled trials with distinct, nonoverlapping investigative sites and
independent monitoring teams renders the possibility of a Type II error
vanishingly small and provides strong credibility for the unexpected lack of
efficacy observed. The most likely causative factors for the efficacy failure in
phase 3 was phenotypic change in the cells (primarily keratinocytes) leading to
batch to batch variability due to the age of the cell banks.
PMID- 27495870
TI - Sortilin facilitates VLDL-B100 secretion by insulin sensitive McArdle RH7777
cells.
AB - Studies examining the relationship between cellular sortilin and VLDL-B100
secretion demonstrate inconsistent results. Current studies explore the
possibility that discrepancies may be related to insulin sensitivity. McArdle
RH7777 cells (McA cells) cultured under serum enriched conditions lose
sensitivity to insulin. Following incubation in serum-free DMEM containing 1%
BSA, McA cells become insulin responsive and demonstrate reduced apo B secretion.
Current studies indicate that insulin sensitive McA cells express lower cellular
sortilin that corresponds with reduction in VLDL-B100 secretion without changes
in mRNA of either sortilin or apo B. When sortilin expression is further reduced
by siRNA knockdown (KD), there are additional decreases in VLDL-B100 secretion. A
crystal structure of human sortilin (hsortilin) identifies two binding sites on
the luminal domain for the N- and C-termini of neurotensin (NT). A small organic
compound (cpd984) was identified that has strong theoretical binding to the N
terminal site. Both cpd984 and NT bind hsortilin by surface plasmon resonance. In
incubations with insulin sensitive McA cells, cpd984 was shown to enhance VLDL
B100 secretion at each level of sortilin KD suggesting cpd984 acted through
sortilin in mediating its effect. Current results support a role for sortilin to
facilitate VLDL-B100 secretion which is limited to insulin sensitive McA cells.
Inconsistent reports of the relationship between VLDL-B100 secretion and sortilin
in previous studies may relate to differing functions of sortilin in VLDL-B100
secretion depending upon insulin sensitivity.
PMID- 27495871
TI - Proximity mapping of human separase by the BioID approach.
AB - Separase is a caspase-like cysteine protease that is best known for its essential
role during the metaphase-to-anaphase transition when it cleaves the cohesin ring
complex that keeps the sister chromatids together. Another important function of
separase is to regulate the process of centriole separation, known as centriole
disengagement, at the end of mitosis. We used proximity-dependent biotin
identification (BioID) to expand our knowledge on the identity of separase's
proximity interactors. We show that separase BioID labeled two domains at the
mother centriole: an area underneath the centriolar appendages and another at the
proximal end of the mother centriole. BioID analysis identified more than 200
proximity interactors of separase, one being the Alstrom Syndrome Protein 1
(ALMS1) at the base of centrioles. Other proximity interactors are the histone
chaperons NAP1L1 and NAP1L4, which localize to the spindle poles during mitosis
and the spindle assembly checkpoint proteins BUBR1, SKA1 and SKA3 that reside at
kinetochores in early mitosis. Finally, we show that depletion of BUBR1 homolog
from Caenorhabditis elegans delayed the recruitment of separase to mitotic
chromosomes, and eventually anaphase onset.
PMID- 27495872
TI - MicroRNA-187-5p suppresses cancer cell progression in non-small cell lung cancer
(NSCLC) through down-regulation of CYP1B1.
AB - Lung cancer remains a leading cause of cancer-associated mortality worldwide and
non-small lung cancer (NSCLC) is responsible for over 80% of lung cancer-related
deaths. Identifying novel molecular biomarker that can inhibit the progression of
lung cancer will facilitate the development of new treatment strategies. Herein,
we demonstrated that miR-187-5p is a tumor-suppressor miRNA in NSCLC progression.
We found that expression of miR-187-5p was decreased obviously in NSCLC tissues.
Down-regulation of miR-187-5p was associated with TNM stage and postoperative
survival. Overexpression of miR-187-5p inhibited the growth and metastasis of
NSCLC cells. The CYP1B1 was a direct target of miR-187-5p and promoted the growth
and metastasis of NSCLC cells. Further study showed that CYP1B1 could reverse the
inhibitory effect of miR-187-5p on growth and metastasis of NSCLC cells. Taken
together, our data highlight the pivotal role of miR-187-5p in the progression of
NSCLC. Thus, miR-187-5p may be a potential prognostic marker and of treatment
relevance for NSCLC progression intervention.
PMID- 27495874
TI - Fear of Dementia.
PMID- 27495873
TI - Silencing Drp1 inhibits glioma cells proliferation and invasion by RHOA/ ROCK1
pathway.
AB - BACKGROUNDS: Dynamin-related protein 1 (Drp1) is a newly discovered therapeutic
target for tumor initiation, migration, proliferation, and chemosensitivity. In
the present study, we aimed to examine the level of expression and distribution
of DRP1 in glioma tissues and explore the concrete mechanism of DRP1 played in
glioma. METHODS: Expression of DRP1 in glioma tissues was determined by
immunohistochemistry staining. The DRP1 gene was knocked down using small
interfering RNA, and was overexpressed using plasmids in glioma cells. To assess
changes in cell function, in vitro assays for invasion and growth were applied.
Protein expression was tested by using Western-blot method. Variation of F-actin
in cells was analyzed using immunofluorescence staining. Interactions between
proteins were determined by co-immunoprecipitation. RESULTS: The protein
expression levels of DRP1 were significantly increased in glioma tissues compared
to the normal brain tissues. Down-regulation of DRP1 decreased cell proliferation
and invasion, and inhibited the formation of pseudopodias and microvillis.
Moreover, a possible link between DRP1 and RHOA was confirmed when interactions
between these two proteins were observed in the cells. CONCLUSIONS: Our results
demonstrated that silencing DRP1 regulated the cytoskeleton remodeling through
inhibiting RHOA/ROCK1 pathway, and thus decreased the proliferation and invasion
of glioma cells.
PMID- 27495875
TI - Regulator of G protein signaling 20 enhances cancer cell aggregation, migration,
invasion and adhesion.
AB - Several RGS (regulator of G protein signaling) proteins are known to be
upregulated in a variety of tumors but their roles in modulating tumorigenesis
remain undefined. Since the expression of RGS20 is elevated in metastatic
melanoma and breast tumors, we examined the effects of RGS20 overexpression and
knockdown on the cell mobility and adhesive properties of different human cancer
cell lines, including cervical cancer HeLa, breast adenocarcinoma MDA-MB-231, and
non-small cell lung carcinoma H1299 and A549 cells. Expression of RGS20 enhanced
cell aggregation, migration, invasion and adhesion as determined by hanging drop
aggregation, wound healing, transwell chamber migration and invasion assays.
Conversely, shRNA-mediated knockdown of endogenous RGS20 impaired these
responses. In addition, RGS20 elevated the expression of vimentin (a mesenchymal
cell marker) but down-regulated the expression of E-cadherin, two indicators
commonly associated with metastasis. These results suggest that the expression of
RGS20 may promote metastasis of tumor cells.
PMID- 27495876
TI - Determination of nicotine, glycerol, propylene glycol and water in electronic
cigarette fluids using quantitative 1 H NMR.
PMID- 27495877
TI - The light switch-off response as a putative rodent test of innate fear.
AB - Recent discussions on the ethics in animal experimentation instigate the
refinement of methods used in Behavioral Neuroscience, particularly regarding
fear/anxiety paradigms. We propose the Light Switch-Off Test (LSOT), based on the
innate motivation to cease an aversive stimulus (bright light), displayed
naturally by rodents in their habitat. Forty-six male adult Wistar rats were
allocated into independent groups: control, diazepam at 1 or 2mg/kg, and meta
Chlorophenylpiperazine (mCPP) at 0.5 or 1mg/kg. The experimental box has two
square compartments, separated by an acrylic portal. In each side of the box,
there is a 40-W incandescent light bulb. After a habituation period in the box,
40 light stimuli (trials lasting up to 20s each) are emitted at random intervals.
By crossing compartments during the lighted period, the rat could switch-off the
stimulus. Parameters observed are the number of switch-off responses (SORs),
latency of SOR and intertrial locomotion. The SOR frequency was higher in rats
treated with mCPP at 1mg/kg, an anxiogenic drug, while diazepam at the doses used
in this study did not produce effects. Animals exposed solely to the box for the
length of the test did not respond in a false positive way. Therefore, the SOR
represents a good index to measure the innate rodent fear of bright-lighten
areas, once they react quickly in order to turn off the stimulus. Among its many
advantages, the LSOT is a simple, replicable, non-invasive and minimally
stressful procedure, since it does not expose animals to excessively aversive
stimulus.
PMID- 27495878
TI - Mild, moderate, and severe intensity cut-points for the Respiratory Distress
Observation Scale.
AB - BACKGROUND: The Respiratory Distress Observation Scale(c) (RDOS) is a means for
assessing respiratory distress when a patient is unable to give a dyspnea self
report. Cut-point determination was needed to guide clinical application. METHOD:
A Receiver Operating Characteristic (ROC) curve analysis was conducted in a
prospective, observation study with inpatients ranked by nurse practitioners (NP)
into levels of respiratory distress. A research assistant simultaneously measured
RDOS blinded to NP ranking. RESULTS: Participants were 84 adults: mean age of
72.6 (SD = 15.2) years, 53.6% male, 77.4% African-American. NP ranking was
distributed: none (30%), mild (26%), moderate (31%), and severe (13%) distress.
RDOS scores ranged 0-13 (M = 4.8, SD = 3). NP ranking was significantly
correlated with RDOS (rho = .91, p < .01). ROC curve analyses yielded cut-points:
none = 0-2, any = 3, mild-moderate = 4-6, and severe >=7 (p < .01). CONCLUSIONS:
Intensity cut-point enhances the clinical utility of the RDOS.
PMID- 27495879
TI - Anuria since birth: does it impact outcome of kidney transplant in infants?
AB - Kidney transplantation (txp) in infants has recently made much progress but
provides a unique challenge in infants anuric since birth. Little data exists on
outcome of renal txp recipients with anuria since birth. Retrospective chart
review was done for outcome of 27 children with wt <=15 kg and they were divided
into two groups: Group A (N=21) with urine output and Group B (N=6) anuric since
birth had their urological complications and long-term outcome compared. Median
age at the time of txp 18 vs 23 months, mean wt 10.8 vs 11.8 kg, and mean ht 77
cm in both, mean follow-up post-txp: 9.4 vs 5.6 years, and neurological problems
were noted in 48% and 33% in Group A and Group B. There was no graft thrombosis
or post-transplant lymphoproliferative disease and only two rejections. Anuric
Group B were older, had more post-txp urological surgeries (66% vs 19%) and UTIs
(66% vs 38%) compared to Group A. The overall graft survival at 1, 5, and 10
years was 96%, 86%, and 70%; patient survival at 1, 5, and 10 years was 96%, 85%,
and 85%. Long-term graft outcomes in small children, anuric prior to txp, were
excellent despite higher rates for UTIs and urological complications.
PMID- 27495880
TI - Effects of multifocal soft contact lenses used to slow myopia progression on
quality of vision in young adults.
AB - PURPOSE: To assess the effects of multifocal soft contact lenses (MF SCLs) used
for myopia control on visual acuity (VA) and subjective quality of vision.
METHODS: Twenty-four young adult myopes had baseline high and low-contrast VAs
and refractions measured and quality of vision assessed by the Quality of Vision
(QoV) questionnaire with single vision SCLs. Additional VA and QoV questionnaire
data were collected immediately after subjects were fitted with Proclear MF SCLs
and again after a 2-week adaptation period of daily lens wear. Data were
collected for two MF SCL designs, incorporating +1.50 and +3.00 D peripheral near
additions, with a week washout period allowed between the two lens trials.
RESULTS: High- and low-contrast VAs were initially reduced with both MF SCL
designs, but subsequently improved to be not significantly reduced in the case of
high-contrast VA by the end of the 2-week adaptation period. The quality of
vision was also reduced, more so with the +3.00 D MF SCL. Quality of Vision (QoV)
scores describing frequency, severity and bothersome nature of visual symptoms
indicated symptoms worsening rather than resolving over the 2-week period,
particularly so with the +3.00 D MF SCL. CONCLUSION: Low and high add MF SCLs
adversely affected vision on initial insertion, with sustained effects on low
contrast VA and QoV scores but not high-contrast VA. Thus, high-contrast VA is
not a suitable surrogate for quality of vision. In prescribing MF SCLs for myopia
control, clinicians should educate patients about these effects on vision.
PMID- 27495881
TI - Cross-sectional study on knowledge of chronic kidney disease among medical
outpatient clinic patients.
AB - BACKGROUND: Chronic kidney disease (CKD) is a major health concern worldwide.
There are limited studies which look into the actual knowledge level of CKD among
the general population both locally and internationally. This study aims to
assess the knowledge level of CKD among patients in a secondary hospital in
Malaysia. METHODS: Consecutive sampling of patients attending the Medical
Outpatient Clinic was performed in this crosssectional study. Respondents were
given self-administered questionnaires which contain questions on demographic
characteristics and knowledge on CKD. RESULTS: Out of 300 respondents, 78.6%
(n=236) of the respondents completed the questionnaire. Majority of respondents
(73.7%, n=174) scored less than 4 out of 7 marks on knowledge on CKD. Respondents
who were younger, males, having higher education status, professionals/executives
and earned higher monthly income were more likely to have a higher mean knowledge
score of CKD. Respondents who have heard of CKD were also significantly
associated with higher mean knowledge score of CKD. CONCLUSION: The study
findings suggest that our Malaysian population is still inadequately informed on
CKD, especially those who are at risk of developing CKD and its complications,
and also among those of the lower socioeconomic group. In order for successful
primary and secondary prevention of CKD, more importance should be placed on
increasing awareness on CKD among these atrisk groups.
PMID- 27495882
TI - Generation and characterisation of human umbilical cord derived mesenchymal stem
cells by explant method.
AB - Mesenchymal stem cells (MSCs) derived from human umbilical cord (UC) have been
considered as an important tool for treating various malignancies, tissue repair
and organ regeneration. Umbilical cord-derived mesenchymal stem cells (UC-MSCs)
are better alternative to MSCs that derived from bone marrow (BM-MSCs) as they
are regarded as medical waste with little ethical concern for research and easily
culture-expanded. In this present study, the foetal distal end of human UC was
utilised to generate MSC by explant method. Upon in vitro culture, adherent cells
with fibroblastic morphology were generated with rapid growth kinetics. Under the
respective inductive conditions, these cells were capable of differentiating into
adipocytes and osteocytes; express an array of standard MSC's surface markers
CD29, CD73, CD90, CD106 and MHC-class I. Further assessment of immunosuppression
activity revealed that MSCs generated from UC had profoundly inhibited the
proliferation of mitogen-activated T lymphocytes in a dosedependent manner. The
current laboratory findings have reinforced the application of explant method to
generate UCMSCs thus, exploring an ideal platform to fulfil the increasing demand
of MSCs for research and potential clinical use.
PMID- 27495883
TI - Prophylactic bilateral internal iliac artery balloon occlusion in the management
of placenta accreta: A 36-month review.
AB - BACKGROUND: The contemporary obstetrician is increasingly put to the test by
rising numbers of pregnancies with morbidly adherent placenta. This study
illustrates our experience with prophylactic bilateral internal iliac artery
occlusion as part of its management. METHODS: Between January 2011 to January
2014, 13 consecutive patients received the intervention prior to scheduled
caesarean delivery for placenta accreta. All cases were diagnosed by
ultrasonography, color Doppler imaging and supplemented with MRI where necessary.
The Wanda balloon(TM) catheter (Boston Scientific, Natick, MA, U.S.A) were placed
in the proximal segment of the internal iliac arteries preceding surgery. This
was followed by a midline laparotomy and classical caesarean section, avoiding
the placenta. Both internal iliac balloons were inflated just before the delivery
of fetus and deflated once haemostasis was secured. Primary outcomes measured
were perioperative blood loss, blood transfusion requirement and the need for ICU
admission. RESULTS: The mean and median intraoperative blood loss were 1076mls+/
707 and 800mls (300-2500) respectively while mean perioperative blood loss was
1261mls+/-946. Just over half of the patients in our series required blood and/or
blood products transfusion. Two patients (15.4%) required ICU admission.
CONCLUSION: Our study suggests that preoperative prophylactic balloon occlusion
of bilateral internal iliac arteries reduces both blood loss and transfusion
requirement in patients with placenta accreta, scheduled to undergo elective
caesarean hysterectomy. It is an adjunct to be considered in the management of a
modern day obstetric problem, although the authors are cautious about
generalizing its benefit without larger, randomized trials.
PMID- 27495884
TI - Community-acquired bacteremia in Paediatrics: Epidemiology, aetiology and
patterns of antimicrobial resistance in a tertiary care centre, Malaysia.
AB - INTRODUCTION: bacteremia continues to be one of the major causes of morbidity and
mortality despite the existence of numerous antimicrobial agents. this study
aimed to provide a Malaysian perspective on paediatric community-acquired
bacteraemia based on the documentation of epidemiology and antimicrobial profile
of the isolated pathogens. METHOD: A retrospective study was conducted by
analysing clinical details, blood cultures and antimicrobial susceptibility
testing results in children between the ages of 0 to 13 years old, who were
admitted to selayang Hospital over an 11-year period from 2001 until 2011. there
were 222 bacteraemia cases and the median age was 11.7 months. the highest number
(39%) of bacteraemia cases occurred between ages one month to one year. the three
most commonly isolated aetiological agents were Staphylococcus aureus (17.1%),
nontyphoidal Salmonella (16.2%), and Streptococcus pneumoniae (12.6%). Almost 8%
of the Staphylococcus aureus isolates were methicillin resistant, while
nontyphoidal Salmonella (Nts) isolates demonstrated 18.4%, 10.5% and 2.6%
resistance towards ampicillin, trimethoprim-sulfamethoxazole and ciprofloxacin
respectively. All Nts isolates were sensitive to ceftriaxone. Streptococcus
pneumoniae isolates showed 17.9% resistance to penicillin. skin and soft tissue
infections as well as lower respiratory tract infections (63.2%) were the main
foci of infections in Staphylococcus aureus bacteraemia. Acute gastroenteritis
(80.0%) and pneumonia (60.8%) were the main presentations of Nts and
Streptococcus pneumoniae bacteraemia respectively. Overall mortality rate was
8.1%. CONCLUSION: Knowledge on the local epidemiology and antibiotic resistance
pattern serves as a significant platform in improving the empiric antibiotic
therapy for patients with community acquired bacteraemia.
PMID- 27495885
TI - Association of Cobb angle progression and neuraxial abnormality on MRI in
asymptomatic Adolescent Idiopathic Scoliosis.
AB - BACKGROUND: Detection of neuraxial abnormality in neurologically asymptomatic
adolescent idiopathic scoliosis (AIS) is crucial prior to surgery. It can only be
detected on magnetic resonance imaging (MRI), which was not routinely done in
this group of patient. On the other hand, whole spine radiographs for measurement
of Cobb angle have been routinely included during clinic follow-up. This study
aimed to determine the correlation between Cobb angle progression and neuraxial
abnormality finding on MRI in asymptomatic AIS. METHODS: A retrospective study
was conducted in the Orthopaedic department of a tertiary hospital. Patients with
asymptomatic AIS aged 10-20 years who attended scoliosis clinic from year 2007 to
2010 was reviewed. Patients who had whole spine MRI and two vertebral radiographs
at least one year apart were further selected. Statistical analysis was done to
see the association between Cobb angle progression and neuraxial abnormality on
MRI. RESULTS: The mean age at first presentation was 14.4 years old. Female
(n=249) to male (n=50) ratio was 5:1. Only 19 patients fulfilled the selection
criteria. There were 5 patients (26.3%) who had neuraxial abnormalities. The mean
curve progression was 7.05 degrees (range from -5 degrees to 28 degrees ).
Patients with and without neuroaxial abnormality showed mean curve progression of
0.6 degrees and 9.36 degrees respectively. There was no significant association
between Cobb angle progression and neuroaxial abnormality (p=1.000). CONCLUSION:
Cobb angle progression is not a reliable indicator for predicting neuroaxial
abnormality in patients with asymptomatic AIS. However, this study stressed the
need to perform MRI prior to operation to document any associated neuraxial
abnormality in clinically asymptomatic AIS patients.
PMID- 27495886
TI - Acute kidney injury following coronary artery bypass graft surgery in a tertiary
public hospital in Malaysia: an analysis of 1228 consecutive cases.
AB - BACKGROUND: Acute kidney injury (AKI) following cardiac surgery is well
established but the reported incidence is variable due to varying definitions and
criteria. Furthermore there is a paucity of such data from Southeast Asia.
OBJECTIVES: To determine the incidence of AKI, the associated risk factors, and
its impact on early mortality and intensive care unit/hospital stay. METHOD: This
is a single centre retrospective observational study to evaluate outcomes on 1260
consecutive patients from a multi-ethnic Southeast Asian population who underwent
a primary isolated coronary artery bypass graft (CABG) operation. Data was
collected from the hospital's electronic database and analysed using basic
descriptive statistics and logistic regression. RESULTS: Overall incidence was
36.2% including 5.5% of patients who required renal replacement therapy (RRT).
Multivariate analysis identified age, insulin-dependent diabetes mellitus (IDDM),
baseline serum creatinine level (SCr), recent myocardial infarction (MI),
cardiopulmonary bypass (CPB) time and intra-aortic balloon pump (IABP) use as
independent risk factors for AKI. For patients who required RRT, the SCr and IDDM
remained independent predictors. Early 30-day mortality (11.5% vs 0.9%) was
significantly higher in patients who developed AKI following CABG. Similarly, AKI
was associated with a slight but statistically significant increase in intensive
care unit (ICU) and hospital stay. CONCLUSION: Better prognostication and
preventative strategies are required to better risk stratify patients undergoing
CABG and optimise utilisation of limited healthcare resources.
PMID- 27495887
TI - Routine measurements of cord arterial blood lactate levels in infants delivering
at term and prediction of neonatal outcome.
AB - OBJECTIVE: Our purpose was to evaluate the relationship between umbilical cord
arterial blood lactate levels with acid base balance to the mode of delivery and
short-term neonatal outcome in a large multiracial population delivering at term
in University of Malaya Medical Centre. MATERIALS AND METHODS: Two thousand two
hundred and twelve patients of more than 37 weeks of gestation with singleton,
liveborn infants with no major anomalies delivering between January 2013 to
December 2013 were analysed. Lactate was measured by using portable Lactate
analyzer that requires 5 MUml of blood and provides the result within 1 minute.
The deliveries took place at the Department of Obstetrics and Gynaecology,
University Malaya Medical Centre, Malaysia where umbilical cord blood sampling
and blood gas analysis is a part of the routine assessment of all newborn.
RESULTS: Gestational age ranged from 37 to 43 weeks (mean 39.05 weeks). The
highest mean arterial cord lactate values were noted among babies delivered
instrumentally (4.87 mmol/L). Infants who had a normal vaginal delivery had the
second highest levels (3.36 mmol/L), followed by infants delivered by emergency
caesarean section (3.30mmol/L). The lowest lactate values were noted in
deliveries by elective caesarean section (3.0mmol/L). Cord arterial lactate
levels were significantly higher among infants born with low Apgar scores (7.02
mmol/L vs 4.6mmol/L, P < 0.001). High arterial cord lactate was a significant
predictor of admission to Neonatal intensive care unit (NICU) was 6.0mmol/L.
Receiver operator curve (ROC) analysis suggests that lactate and pH are virtually
equivalent in their correlation with adverse neonatal outcome. CONCLUSION: Cord
lactate levels are significantly related to the mode of delivery and is
equivalent to cord arterial pH in predicting adverse neonatal outcomes, with
similar efficacies; however, its simplicity, less sampling failure and low cost
makes lactate analysis an interesting alternative in obstetric care.
PMID- 27495888
TI - Serotype prevalence of Streptococcus pneumoniae in Malaysia - the need for
carriage studies.
AB - Pneumococcal disease, caused by the bacterium Streptococcus pneumoniae, is a
major burden to global health. Although the World Health Organisation (WHO)
strongly recommends the inclusion of pneumococcal conjugate vaccines in national
immunisation programmes (NIP's) worldwide, this has not occurred in many
countries in the WHO South East Asia and Western Pacific regions - particularly
longstanding middle-income countries. It is widely accepted that carriage of S.
pneumoniae is a precursor to developing any pneumococcal disease. The reduction
in pneumococcal disease from vaccine serotypes (VT) following widespread
implementation of the pneumococcal conjugate vaccine (PCV) is believed to be
through the direct immunogenic protective effect of immunised individuals as well
as indirectly through herd immunity diminishing the incidence of disease in
nonimmunised individuals. In Malaysia, pneumococcal disease is not included in
national surveillance programmes and although PCVs have been licensed, they have
not been included in the NIP. Hence, the vaccine is only available privately and
the majority of the population is not able to afford it. There is an urgent need
to develop surveillance programmes in Malaysia to include pneumococcal serotype
data from carriage and invasive disease so that it may help guide national
vaccine policy prior to a decision being taken on the inclusion of PCVs in the
NIP.
PMID- 27495889
TI - Thoracic Aortic Aneurysm as A Cause of Ortner's Syndrome - A Case Series.
AB - Hoarseness due to left recurrent laryngeal nerve paralysis was first described in
1897 by Norbert Ortner. Various cardiopulmonary and thoracic arch aorta
pathologies associated with left recurrent laryngeal nerve palsy have been
described over the last 100 years and is also known as cardio-vocal syndrome. We
report our experience with seven cases of Ortners syndrome due to thoracic aortic
aneurysm with compression of the left recurrent laryngeal nerve and resultant
hoarseness.
PMID- 27495890
TI - Allergic reaction to stainless steel sternotomy wires requiring removal: A case
report and literature review.
AB - Hypersensitivity to stainless steel sternal sutures are an uncommon occurrence.
We present a case of such a patient who developed chronic tissue overgranulation
over a sternotomy wound eight weeks post-operatively. Primary suspicion was
infection, a more common complication however radiological and laboratory
investigation showed otherwise. Conservative management provided limited
ephemeral success. After ensuring adequate sternal bone healing, the sutures and
granulation tissue were eventually surgically removed without complication and
the reoperated wound healed well.
PMID- 27495891
TI - Polypoid endometriosis of post vaginal fornix: utility of MRI imaging of pelvis
with diffusion weighted imaging for diagnosis.
AB - Polypoid endometriosis is an uncommon variant of endometriosis which can mimic
malignancy due to its presentation as masses. We present a case of polypoid
endometriosis which simulated cervical malignancy both on clinical examination
and on computed tomography (CT) scanning and discuss how magnetic resonance (MR)
imaging, in particular Diffusion Weighted Imaging (DWI), can help to distinguish
this condition from true malignancy and avoid invasive surgery.
PMID- 27495892
TI - Cardiac tamponade: a rare but preventable complication of central venous catheter
in neonates.
AB - Pericardial effusion with cardiac tamponade is a rare and life-threatening
complication of peripherally inserted central catheter (PICC) in a neonate. We
report a 33-week preterm neonate who had sudden clinical deterioration at day
seven of total parenteral nutrition regime via PICC. Recognition of pericardial
effusion with cardiac tamponade in neonates with a PICC requires a high index of
suspicion and steps in prevention include proper catheter tip placement and
continuous monitoring of line position and function.
PMID- 27495893
TI - Primary breast tuberculosis (TB) in a patient with known invasive breast
carcinoma: A case report.
AB - Breast tuberculosis (TB) is rare even in endemic countries. Most of these cases
occur as secondary TB due to a concurrent infection. Primary breast TB is
diagnosed when it is the only site of disease without other foci of infection.
The presentation of primary breast TB may often mimic carcinoma of the breast.
While imaging is not specific, histopathology provides a definitive diagnosis.
Here, we present a case of primary breast TB in a breast cancer patient and
review the literature.
PMID- 27495894
TI - Gram-negative infection as an unusual cause of endocarditis in a hemodialysis
patient.
AB - Gram-negative endocarditis is rare and it has high mortality if there is a delay
in diagnosis and treatment. Gram-negative organisms should be considered in the
differential diagnosis of IE in hemodialysis patients. Central lineassociated
bloodstream infections (CLABSIs) can be prevented by following sterile measures
during catheter insertion and proper management of catheter site.
PMID- 27495895
TI - Sinonasal angioleiomyoma.
AB - BACKGROUND: Angioleiomyoma of the nasal cavity is an extremely rare benign
neoplasm. It usually occurs in the lower extremities. Up to date, only few cases
of angioleiomyoma have been reported. First case of angioleiomyoma of nasal
cavity was reported in 1966. We report a rare case of angioleiomyoma arising from
the right maxillary sinus. CASE REPORT: A 43-year-old lady presented with
recurrent epistaxis and right nasal obstruction for two months duration. Clinical
examination revealed a huge right nasal mass obstructing the right nasal cavity.
The tumour was excised completely via endoscopic endonasal surgical approach.
Histopathological examination confirmed the tumour is sinonasal angioleiomyoma.
Postoperatively, she recovered well without any recurrence after a year of
followup. CONCLUSION: This tumour has an excellent prognosis and recurrence is
extremely rare if excised completely.
PMID- 27495896
TI - DEHP exposure in utero disturbs sex determination and is potentially linked with
precocious puberty in female mice.
AB - Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to
be associated with female reproductive toxicity. Previous studies found that DEHP
inhibited follicle growth and decreased estradiol levels in adult female mice.
However, limited information is available on the link between in utero DEHP
exposure and ovarian development in female mouse offspring. The present study
evaluates the disturbances in regulatory genes involved in female sex
determination and the ovarian outcomes in fetal and postnatal female mice treated
with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with
the dosage regime beginning at human relevant exposure levels. After in utero
DEHP exposure, increased follicular atresia was observed in the female pups at
postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst
was significantly downregulated by DEHP above 2mg/kg/d at PND 1 and 21. This
suggests that lesion of granulosa cell differentiation and disturbance of
follicle development in postnatal female mice. The expression of Cyp11a1 and Star
were significantly downregulated by in utero DEHP exposure, indicating effects on
estradiol biosynthesis. The female sex determination pathway was disturbed in
fetus by DEHP at 2mg/kg/d and above during the critical time window of sex
determination causing significant upregulation of Foxl2, Wnt4, beta-catenin and
Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount
in situ hybridization (WISH). These results suggest a possible association
between in utero DEHP exposure and precocious puberty in the postnatal life of
mice offspring, where disturbance of the sex determination regulating pathway
acted as an important mechanism.
PMID- 27495897
TI - Disruption of motor behavior and injury to the CNS induced by 3-thienylboronic
acid in mice.
AB - The scarcity of studies on boron containing compounds (BCC) in the medicinal
field is gradually being remedied. Efforts have been made to explore the effects
of BCCs due to the properties that boron confers to molecules. Research has shown
that the safety of some BCCs is similar to that found for boron-free compounds
(judging from the acute toxicological evaluation). However, it has been observed
that the administration of 3-thienylboronic acid (3TB) induced motor disruption
in CD1 mice. In the current contribution we studied in deeper form the disruption
of motor performance produced by the intraperitoneal administration of 3TB in
mice from two strains (CD1 and C57BL6). Disruption of motor activity was
dependent not only on the dose of 3TB administered, but also on the DMSO
concentration in the vehicle. The ability of 3TB to enter the Central Nervous
System (CNS) was evidenced by Raman spectroscopy as well as morphological effects
on the CNS, such as loss of neurons yielding biased injury to the substantia
nigra and striatum at doses >=200mg/kg, and involving granular cell damage at
doses of 400mg/kg but less injury in the motor cortex. Our work acquaints about
the use of this compound in drug design, but the interesting profile as
neurotoxic agent invite us to study it regarding the damage on the motor system.
PMID- 27495898
TI - Continuous Acquisition of MHC:Peptide Complexes by Recipient Cells Contributes to
the Generation of Anti-Graft CD8+ T Cell Immunity.
AB - Understanding the evolution of the direct and indirect pathways of
allorecognition following tissue transplantation is essential in the design of
tolerance-promoting protocols. On the basis that donor bone marrow-derived
antigen-presenting cells are eliminated within days of transplantation, it has
been argued that the indirect response represents the major threat to long-term
transplant survival, and is consequently the key target for regulation. However,
the detection of MHC transfer between cells, and particularly the capture of
MHC:peptide complexes by dendritic cells (DCs), led us to propose a third,
semidirect, pathway of MHC allorecognition. Persistence of this pathway would
lead to sustained activation of direct-pathway T cells, arguably persisting for
the life of the transplant. In this study, we focused on the contribution of
acquired MHC-class I on recipient DCs during the life span of a skin graft. We
observed that MHC-class I acquisition by recipient DCs occurs for at least 1
month following transplantation and may be the main source of alloantigen that
drives CD8+ cytotoxic T cell responses. In addition, acquired MHC-class I:peptide
complexes stimulate T cell responses in vivo, further emphasizing the need to
regulate both pathways to induce indefinite survival of the graft.
PMID- 27495900
TI - Enteric fever in India: current scenario and future directions.
AB - Enteric fever is a major cause of morbidity and mortality in tropical areas
worldwide. The Indian subcontinent bears the brunt of the disease, both in terms
of absolute case numbers and drug-resistant strains. Recent phylogenetic studies
suggest that the multidrug-resistant clade H58 originated in India and
subsequently expanded through Asia and Africa. In Africa, it caused unrecognised
outbreaks in areas previously considered free of the disease. In this study, we
discuss the current status of enteric fever in India, the factors preventing its
control and its future directions in this rapidly developing nation.
PMID- 27495901
TI - Exploring and Expanding the Fatty-Acid-Binding Protein Superfamily in Fasciola
Species.
AB - The liver flukes Fasciola hepatica and F. gigantica infect livestock worldwide
and threaten food security with climate change and problematic control measures
spreading disease. Fascioliasis is also a foodborne disease with up to 17 million
humans infected. In the absence of vaccines, treatment depends on triclabendazole
(TCBZ), and overuse has led to widespread resistance, compromising future TCBZ
control. Reductionist biology from many laboratories has predicted new
therapeutic targets. To this end, the fatty-acid-binding protein (FABP)
superfamily has proposed multifunctional roles, including functions intersecting
vaccine and drug therapy, such as immune modulation and anthelmintic
sequestration. Research is hindered by a lack of understanding of the full FABP
superfamily complement. Although discovery studies predicted FABPs as promising
vaccine candidates, it is unclear if uncharacterized FABPs are more relevant for
vaccine formulations. We have coupled genome, transcriptome, and EST data mining
with proteomics and phylogenetics to reveal a liver fluke FABP superfamily of
seven clades: previously identified clades I-III and newly identified clades IV
VII. All new clade FABPs were analyzed using bioinformatics and cloned from both
liver flukes. The extended FABP data set will provide new study tools to research
the role of FABPs in parasite biology and as therapy targets.
PMID- 27495899
TI - CAT3, a novel agent for medulloblastoma and glioblastoma treatment, inhibits
tumor growth by disrupting the Hedgehog signaling pathway.
AB - Medulloblastoma (MB) and glioblastoma (GBM) are the most prevalent malignant
brain tumors. The identification of novel therapeutic strategies is urgent for MB
and GBM patients. Herein, we discovered 13a-(S)-3-Hydroxyl-6,7
dimethoxyphenanthro[9,10-b]-indolizidine (PF403) strongly exhibited inhibitory
activity against Hedgehog (Hh) pathway-hyperactivated MB and GBM cells with a 50%
inhibitory concentration (IC50) of 0.01 nM. CAT3 was designed and synthesized as
the prodrug of PF403 and displayed significant in vivo efficacy against MB and
GBM. Mechanistic study revealed that CAT3 inhibited MB and GBM primarily by
interrupting the Hh signaling pathway. At the molecular level, PF403 inhibited
the cell surface accumulation of the Smoothened (Smo) receptor by directly
binding or enhancing the interaction of Smo with the repressor Ptch1.
Furthermore, PF403 significantly repressed Gli1 nuclear accumulation and
transcription by promoting Sufu-Gli1 and PKA-Gli1 interactions. Collectively, our
studies support the hypothesis that CAT3 is a promising therapeutic agent for the
treatment of Hh-driven MB and GBM.
PMID- 27495903
TI - Fatty acid composition of birds and game hunted by the Eastern James Bay Cree
people of Quebec.
AB - BACKGROUND: Indigenous peoples have traditionally relied on foods hunted and
gathered from their immediate environment. The Eastern James Bay Cree people
consume wild game and birds, and these are believed to provide health as well as
cultural benefits. OBJECTIVE: To determine the fatty acid (FA) composition of
traditional game and bird meats hunted in the Eastern James Bay area. DESIGN:
Harvested traditional game and birds were analysed for FA composition. A total of
52 samples from six wildlife species were collected in the areas of Chisasibi,
Waswanipi and Mistissini, of which 35 were from birds (white partridge and Canada
goose) and 17 were from land animals (beaver, moose, caribou and black bear).
RESULTS: Alpha-linolenic acid (ALA) was the most common n-3 polyunsaturated fatty
acid (PUFA) in all samples except for the black bear flesh, in which it was
docosapentaenoic acid (DPAn-3). In white partridge, beaver and caribou flesh,
PUFAs (mainly n-6) were the most common category of fats while in goose, moose
and black bear flesh, monounsaturated fatty acids (MUFAs) predominated. In all
species, saturated fatty acids (SFAs) were the second most important FAs. It
would appear that in the land animals and birds that were analysed, the SFA
content was lower and the PUFA content was higher than store-bought meats giving
them a more heart-healthy profile. CONCLUSIONS: These results showed that the FA
composition of game species consumed by the James Bay Cree population is
consistent with a beneficial diet and that traditional foods should continue to
be promoted among the Cree people to provide better physical health as well as
social and spiritual benefits.
PMID- 27495902
TI - Oral microbial community typing of caries and pigment in primary dentition.
AB - BACKGROUND: Black extrinsic discoloration in primary dentition is a common
clinical and aesthetic problem that can co-occur with dental caries, the most
common oral diseases in childhood. Although the role of bacteria in the formation
of pigment and caries in primary dentition is important, their basic features
still remain a further mystery. METHODS: Using targeted sequencing of the V1-V3
hypervariable regions of bacterial 16S ribosomal RNA (rRNA) genes, we obtained a
dataset consisting of 831,381 sequences from 111 saliva samples and 110
supragingival plaque samples from 40 patients with pigment (black extrinsic
stain), 20 with caries (obvious decay), and 25 with both pigment and caries and
from 26 healthy individuals. We applied a Dirichlet multinomial mixture (DMM)
based community typing approach to investigate oral microbial community types.
RESULTS: Our results revealed significant structural segregation of microbial
communities, as indicated by the identification of two plaque community types (A
and B) and three saliva community types (C-E). We found that the independent
occurrence of the two plaque community types, A and B, was potentially associated
with our oral diseases of interest. For type A, three co-occurring bacterial
genus pairs could separately play a potential role in the formation of pigment
(Leptotrichia and Fusobacterium), caries (unclassified Gemellales and
Granulicatella), and mixed caries and pigment (Streptococcus and Mogibacterium).
For type B, three co-occurring bacterial genera (unclassified Clostridiaceae,
Peptostreptococcus, and Clostridium) were related to mixed pigment and caries.
Three dominant bacterial genera (Selenomonas, Gemella, and Streptobacillus) were
linked to the presence of caries. CONCLUSIONS: Our study demonstrates that plaque
associated oral microbial communities could majorly contribute to the formation
of pigment and caries in primary dentition and suggests potential clinical
applications of monitoring oral microbiota as an indicator for disease diagnosis
and prognosis.
PMID- 27495904
TI - Puerperal sepsis, the leading cause of maternal deaths at a Tertiary University
Teaching Hospital in Uganda.
AB - BACKGROUND: Maternal mortality is highest in sub-Saharan Africa. In Uganda, the
WHO- MDG 5 (aimed at reducing maternal mortality by 75 % between 1990 and 2015)
has not been attained. The current maternal mortality ratio (MMR) in Uganda is
438 per 100,000 live births coming from 550 per 100,000 in 1990. This study sets
out to find causes and predictors of maternal deaths in a tertiary University
teaching Hospital in Uganda. METHODS: The study was a retrospective unmatched
case control study which was carried out at the maternity unit of Mbarara
Regional Referral Hospital (MRRH). The sample included pregnant women aged 15-49
years admitted to the Maternity unit between January 2011 and November 2014. Data
from patient charts of 139 maternal deaths (cases) and 417 controls was collected
using a standard audit/data extraction form. Multivariable logistic regression
analysis was used to assess for the factors associated with maternal mortality.
RESULTS: Direct causes of mortality accounted for 77.7 % while indirect causes
contributed 22.3 %. The most frequent cause of maternal mortality was puerperal
sepsis (30.9 %), followed by obstetric hemorrhage (21.6 %), hypertensive
disorders in pregnancy (14.4 %), abortion complications (10.8 %). Malaria was the
commonest indirect cause of mortality accounting for 8.92 %. On multivariable
logistic regression analysis, the factors associated with maternal mortality
were: primary or no education (OR 1.9; 95 % CI, 1.0-3.3); HIV positive sero
status (OR, 3.6; 95 % CI, 1.9-7.0); no antenatal care attendance (OR 3.6; 95 %
CI, 1.8-7.0); rural dwellers (OR, 4.5; 95 % CI, 2.5-8.3); having been referred
from another health facility (OR 5.0; 95 % CI, 2.9-10.0); delay to seek health
care (delay-1) (OR 36.9; 95 % CI, 16.2-84.4). CONCLUSIONS: Most maternal deaths
occur among mothers from rural areas, uneducated, HIV positive, unbooked mothers
(lack of antenatal care), referred mothers in critical conditions and mothers
delaying to seek health care. Puerperal sepsis is the leading cause of maternal
deaths at Mbarara Regional Referral Hospital. Therefore more research into
puerperal sepsis to describe the microbiology and epidemiology of sepsis is
recommended.
PMID- 27495905
TI - Quality of Life in Portuguese Patients with Diabetic Foot Ulcer Before and After
an Amputation Surgery.
AB - PURPOSE: Diabetic foot ulcer (DFU) including amputation surgery has serious
consequences for patients, the family and healthcare services. DFU affects not
only the physical health-related quality of life (HRQoL) of patients but also
their mental well-being. The aims of this study were to find the predictors of
HRQoL after surgery, to analyse differences in HRQoL, before and after surgery,
and to explore the moderating role of a first versus previous amputation(s) in
the relationship between physical and mental HRQoL, before and after surgery, in
patients with DFU. METHOD: A longitudinal study comprising 108 Portuguese
patients was conducted during the period of hospitalization before the surgery
and at a follow-up consultation. Participants completed a socio-demographic
questionnaire and the SF-36 to assess HRQoL. RESULTS: Physical and mental HRQoL
before surgery predicted HRQoL after surgery, as well as the number of diabetes
complications and having received a re-amputation. Physical HRQoL decreased after
surgery, but there were no differences on mental HRQoL. Having a previous
amputation was a moderator between physical and mental HRQoL before and after
surgery. CONCLUSION: The results help to identify the most vulnerable patients at
risk of having lower HRQoL after surgery, allowing interventions to be tailored
to patients' needs in order to promote their quality of life.
PMID- 27495907
TI - Timing and type of immune checkpoint therapy affect the early radiographic
response of melanoma brain metastases to stereotactic radiosurgery.
PMID- 27495906
TI - Percutaneous irreversible electroporation for breast tissue and breast cancer:
safety, feasibility, skin effects and radiologic-pathologic correlation in an
animal study.
AB - BACKGROUND: To study the safety, feasibility and skin effects of irreversible
electroporation (IRE) for breast tissue and breast cancer in animal models.
METHODS: Eight pigs were used in this study. IRE was performed on the left
breasts of the pigs with different skin-electrode distances, and the right
breasts were used as controls. The electrodes were placed 1-8 mm away from the
skin, with an electrode spacing of 1.5-2 cm. Imaging and pathological
examinations were performed at specific time points for follow-up evaluation.
Vital signs, skin damage, breast tissue changes and ablation efficacy were also
closely observed. Eight rabbit models with or without VX2 breast tumor
implantations were used to further assess the damage caused by and the repair of
thin skin after IRE treatment for breast cancer. Contrast-enhanced ultrasound and
elastosonography were used to investigate ablation efficacy and safety. RESULTS:
During IRE, the color of the pig breast skin reversibly changed. When the skin
electrode distance was 3 mm, the breast skin clearly changed, becoming white in
the center and purple in the surrounding region during IRE. One small purulent
skin lesion was detected several days after IRE. When the skin-electrode distance
was 5-8 mm, the breast skin became red during IRE. However, the skin architecture
was normal when evaluated using gross pathology and hematoxylin-eosin staining.
When the skin-electrode distance was 1 mm, skin atrophy and yellow glabrescence
occurred in the rabbit breasts after IRE. When the skin-electrode distance was
>=5 mm, there was no skin damage in the rabbit model regardless of breast cancer
implantation. After IRE, complete ablation of the targeted breast tissue or
cancer was confirmed, and apoptosis was detected in the target tissue and
outermost epidermal layer. In the ablated breasts of the surviving animals,
complete mammary regeneration with normal skin and hair was observed.
Furthermore, no massive fibrosis or mass formation were detected on ultrasound or
through hematoxylin-eosin staining. CONCLUSIONS: After IRE, the skin architecture
was well preserved when the skin-electrode distance was >=5 mm. Moreover, breast
regeneration occurred without mass formation or obvious fibrosis.
PMID- 27495908
TI - The River Ruhr - an urban river under particular interest for recreational use
and as a raw water source for drinking water: The collaborative research project
"Safe Ruhr" - microbiological aspects.
AB - Along the intense industrialization of the Ruhr valley (Germany), the River Ruhr
became increasingly polluted. Over time, using it for recreational purposes
became a serious health hazard and bathing was banned due to chemical and
microbiological risks. The purpose of the collaborative project "Safe Ruhr" was
to verify the current status and to provide a scientific basis for lifting the
bathing ban. As the river also provides a raw water source for drinking water
production, it was investigated how well the treatment procedures control
possible hygienic risks. As study area, the barrier Lake Baldeney was chosen as
it embraces earlier bathing sites and tributes to river bank filtration water for
drinking water treatment plants. The hygienic condition of the river water was
determined over 18 months by measuring general physical, chemical and
microbiological water quality parameters including fecal indicators, bacterial
obligate and facultative pathogens, parasitic protozoa, enteric viruses and
schistosome parasites (Trichobilharzia). Samples were taken at eight locations
including sites before and after receiving the discharge of stormwater and
treated wastewater, potential future bathing sites and a raw water abstraction
point for potable water production. In summary, for all investigated physico
chemical parameters no significant difference between the eight investigated
sampling locations on a distinct sampling date were observed. This study focused
on hygienically relevant bacteria and parasitic protozoa. Fecal indicators,
Escherichia coli, intestinal enterococci and Clostridium perfringens as well as
coliform bacteria were detected in 94-100% of the water samples. Enteric
pathogens, including Campylobacter spp. and Salmonella enterica, were isolated
from 33% and 28% of the samples, respectively, in relatively low concentrations.
Among the environmental facultative pathogens, P. aeruginosa was detected at a
high frequency of 82% of all samples, but in low numbers, while Aeromonas spp.
were found in all water samples in relative high concentrations. The levels of
all target organisms were not clearly associated with sources of pollution, with
the exception of slightly enhanced numbers of coliform bacteria and E. coli
downstream of a sewage discharge point from a wastewater treatment plant.
Seasonal variations were observed with higher detection rates of Campylobacter
spp. in winter and S. enterica in autumn and winter in contrast to the other
bacterial groups, which showed no significant fluctuations throughout the year.
Precipitation within two days prior to sampling resulted in a trend of enhanced
numbers of coliform bacteria, E. coli, intestinal enterococci and Aeromonas.
Sampling and analysis of parasitic protozoa was carried out in accordance to the
European bathing water guideline and the ISO 15553 method. Characteristics of the
river (flow, vegetation, birds protection zone, bathing of people, sewage etc.)
were compared to the number of organisms detected. All in all 184 samples were
investigated for Cryptosporidium spp. and Giardia spp. 80% of the samples were
positive for Giardia spp. with a mean of 5cysts/100l (0.1-157.9). Highest values
were achieved in autumn and winter, lowest values during the assumed bathing
season. There seemed to be a trend to lower values in and after a reservoir in
the river course, but with no statistical significance. A statistical
significance could be shown for higher concentrations after heavy rainfall that
led to discharge of combined sewage overflows in the city of Essen. Only 29% of
the samples were positive for Cryptosporidium spp. with a single maximum value of
27.7 and all other concentrations below 5 oocysts/100l. On a low level there
seemed to be slightly higher findings during summer and bathing season than in
autumn and winter. No correlation to heavy rainfall could be found. The findings
correspond to earlier results from the River Rhine (Germany). The influence of
sewage on the water quality of the Ruhr could be shown from the correlation of
Giardia load and activity of combined sewage overflows after heavy rainfall. The
rare and low findings of Cryptosporidium spp. lead to the same conclusion, that
microbial water quality in the investigation area is rather influenced from
sewage water than from diffuse water sources into the River Ruhr.
PMID- 27495909
TI - [Editorial].
PMID- 27495910
TI - [Short version of the German S3 guideline for bladder cancer].
AB - Urinary bladder cancer is the second most common cancer of the urogenital system.
The Guideline Program in Oncology (Leitlinienprogramm Onkologie) of the
Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft
der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), the German Cancer
Society (Deutsche Krebsgesellschaft) and the German Cancer Aid (Deutsche
Krebshilfe) as well as 31 different medical societies have developed the first
interdisciplinary, evidence-based German guideline for bladder cancer. This short
version presents the resulting series of diagnostic and therapeutic
recommendations which were based on a systematic literature search and approved
by a team of bladder cancer experts. The full version is available under
http://leitlinienprogramm-onkologie.de/ .
PMID- 27495911
TI - Practical achievements on biomass steam gasification in a rotary tubular coiled
downdraft reactor.
AB - Today, the impending stringent environmental norms and concerns about the
depletion of fossil fuel reserves have added impetus on development of cutting
edge technologies for production of alternative fuels from renewable sources,
like biomass. The concept of biomass pyro-gasification offers a platform for
production of (a) hydrogen, (b) hydrocarbons and (c) value added chemicals, etc.
In this context, there exists potential for hydrogen production from biomass by
superheated steam gasification. Apart from H2, gaseous products of biomass steam
gasification contain CO, CH4 and other hydrocarbons that can be converted to
hydrogen through cracking, steam reforming and water gas shift reactions. In the
present work, the characteristics of biomass steam gasification in an
indigenously designed rotary tubular coiled-downdraft reactor for high value
gaseous fuel production from rice husk was studied through a series of
experiments. The robust reactor system enhances biomass conversion to gaseous
products by improved mass and heat transfer within the system induced by a coiled
flow pattern with increased heat transfer area. Also, the system has improved
upon the reliability of operation and offered greater continuity of the process
and easier control in comparison with a conventional process by making use of an
innovative gas cooler assembly and efficient venturi-mixing system for biomass
and steam. Subsequently, the effects of reactor temperature, steam-to-biomass
ratio and residence time on overall product gas yield and hydrogen yield were
investigated. From the experimental results, it can be deduced that an optimum
reactor temperature of 750 degrees C, steam-to-biomass ratio of 2.0 and a
residence time of 3.0 min contributed highest gas yield (1.252 Nm3 kg-1 moisture
free biomass). Based on the obtained experimental results, a projected potential
hydrogen yield of 8.6 wt% of the moisture-free biomass could be achieved, and is
also practical for production of pure hydrogen.
PMID- 27495912
TI - Surgical control and margin status after robotic and open cystectomy in high-risk
cases: Caution or equivalence?
AB - PURPOSE: The benefits of robotic-assisted radical cystectomy (RARC) are unclear,
especially in patients with high-risk disease (pT3/T4). We evaluated pathological
and postoperative outcomes of RARC versus open radical cystectomy (ORC) in these
patients. METHODS: We identified bladder cancer patients treated with RARC or ORC
from January 2010-August 2014. Clinicodemographic factors were examined for
potential confounding. Our primary outcome of interest was positive soft-tissue
surgical margins (STSMs). Secondary outcomes included post-operative
complications and length of stay (LOS). We used logistic regression to define the
association between clinical factors with outcomes of interest, focusing on
patients with locally advanced disease. RESULTS: We identified 472 patients
treated with ORC (407, 86.2 %) or RARC (65, 13.8 %) of which 215 (45.6 %) were
high-risk cases based on advanced pathologic stage (pT3/4). RARC patients were
more commonly men (96.9 vs. 73.2 %, p < 0.01), had better performance status
(ECOG 0, 78.5 vs. 59.7 %, p = 0.031), and received less neoadjuvant chemotherapy
(21.5 vs. 39.3 %, p = 0.006). Total (52.3 vs. 59.7 %, p = 0.26) and high-grade
complication rates (13.8 vs. 19.7 %, p = 0.27) were similar, but median LOS was
shorter after RARC (6 vs. 7 days, p < 0.01). On multivariate analysis, prior
pelvic radiation (OR: 4.78, 95 % CI: 2.16-10.57), and advanced tumor stage (OR:
3.06, 95 % CI: 1.56-6.03) were independently associated with positive STSMs in
high-risk patients but robotic surgical approach was not (OR: 0.81, 95 % CI: 0.29
2.30; p = 0.69). CONCLUSION: RARC had similar short-term postoperative outcomes
compared to ORC and did not compromise oncological control in patients with
extravesical disease.
PMID- 27495913
TI - Effect of dosimeter's position on occupational radiation extremity dose
measurement for nuclear medicine workers during (18)F-FDG preparation for PET/CT.
AB - BACKGROUND: The recent spread of positron emission tomography-computed tomography
(PET/CT) poses extremity dosimetry challenges. The question arose whether the
radiation dose measured by the ring thermoluminescent dosimeter usually worn on
the proximal phalanx (P1) of the index finger measures doses that are
representative of the true doses received by the upper extremities of the
operators. A prospective individual dosimetry study was performed in which the
personal equivalent dose Hp (0.07) received during a specific 2-[(18)F]fluoro-2
deoxy-D-glucose ((18)F-FDG) manual dose-dispensing procedure was measured in a
paired design by two operational personal electronic dosimeters fitted on the
palm side of the index finger, namely in the P1 and distal phalanx (P3)
positions. The study participants were ten nuclear medicine technologists working
in two nuclear medicine departments. The personal equivalent radiation doses
received by the palm side of the proximal phalanx of the index finger [Hp
(0.07)P1] and that received by the distal phalanx [Hp (0.07)P3] were compared.
RESULTS: The median Hp (0.07)P3/Hp (0.07)P1 ratio per participant varied between
1.0 and 2.5 (based on 23 to 31 measurements per participant). The 271 paired
measurements revealed a crude Hp (0.07)P3/Hp (0.07)P1 ratio of 1.67,
significantly different from 1 (p = 0.0004, 95 % CI [1.35-2.07]). When adjusted
on participant's gender and mother vial activity, the ratio was similar (1.53, p
= 0.003, 95 % CI [1.22-1.92]). CONCLUSIONS: The study demonstrated a significant
disparity that may exist between the radiation doses measured in the P1 and P3
positions of operators during (18)F-FDG manipulation. These findings emphasize
the importance of performing workplace dosimetry studies adapted to each
radiopharmaceutical and manipulation thereof, aiming to guarantee optimal
workers' dosimetry monitoring schemes. TRIAL REGISTRATION: Hospital Nursing and
Paramedical Research Program (PHRIP, 2011-2013) from the French Ministry of
Health (DGOS), http://social-sante.gouv.fr/IMG/pdf/Resultats_PHRIP_2011.pdf.
PMID- 27495914
TI - Abdo-Man: a 3D-printed anthropomorphic phantom for validating quantitative SIRT.
AB - BACKGROUND: The use of selective internal radiation therapy (SIRT) is rapidly
increasing, and the need for quantification and dosimetry is becoming more
widespread to facilitate treatment planning and verification. The aim of this
project was to develop an anthropomorphic phantom that can be used as a
validation tool for post-SIRT imaging and its application to dosimetry. METHOD:
The phantom design was based on anatomical data obtained from a T1-weighted
volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.5 T MRI
scanner. The liver, lungs and abdominal trunk were segmented using the Hermes
image processing workstation. Organ volumes were then uploaded to the Delft
Visualization and Image processing Development Environment for smoothing and
surface rendering. Triangular meshes defining the iso-surfaces were saved as
stereo lithography (STL) files and imported into the Autodesk(r) Meshmixer
software. Organ volumes were subtracted from the abdomen and a removable base
designed to allow access to the liver cavity. Connection points for placing
lesion inserts and filling holes were also included. The phantom was manufactured
using a Stratasys Connex3 PolyJet 3D printer. The printer uses stereolithography
technology combined with ink jet printing. Print material is a solid acrylic
plastic, with similar properties to polymethylmethacrylate (PMMA). RESULTS:
Measured Hounsfield units and calculated attenuation coefficients of the material
were shown to also be similar to PMMA. Total print time for the phantom was
approximately 5 days. Initial scans of the phantom have been performed with Y-90
bremsstrahlung SPECT/CT, Y-90 PET/CT and Tc-99m SPECT/CT. The CT component of
these images compared well with the original anatomical reference, and
measurements of volume agreed to within 9 %. Quantitative analysis of the phantom
was performed using all three imaging techniques. Lesion and normal liver
absorbed doses were calculated from the quantitative images in three dimensions
using the local deposition method. CONCLUSIONS: 3D printing is a flexible and
cost-efficient technology for manufacture of anthropomorphic phantom. Application
of such phantoms will enable quantitative imaging and dosimetry methodologies to
be evaluated, which with optimisation could help improve outcome for patients.
PMID- 27495915
TI - Ischemia/reperfusion injury in vascularized tissue allotransplantation: tissue
damage and clinical relevance.
AB - PURPOSE OF REVIEW: Ischemia and reperfusion injury (IRI) in vascularized tissue
allotransplantation (VCA) remain largely undefined. Because VCA is comprised of
different tissues, the sensitivity towards IRI may not be uniform. We, herein,
attempt to address mechanistic aspects of IRI in VCA and provide a summary on
potential technologies and targets for amelioration or treatment of IRI in this
novel field. RECENT FINDINGS: IRI results in a loosened architecture of
musculature, hypertrophic, centrally located cell nuclei as well as a high degree
of neovascularization. Mitochondria in muscle tissue show a high degree of
degeneration after prolonged ischemia whereas the ultrastructure remains normal
after short cold ischemia time (CIT). Muscle cell necrosis accompanied by a
diffuse inflammatory infiltrate and vasculopathy of small vessels is observed
after 30 h of CIT. Nerves revealed a high degree of separation and vacuolization
of myelin lamellae because of Wallerian degeneration. Approaches to minimize IRI
include use of novel preservation solutions, administration of antioxidative and
anti-inflammatory molecules/drugs as well as the implementation of machine
perfusion in the setting of VCA. SUMMARY: Hand and face transplantations are
logistically challenging procedures. Optimal planning and a highly congruent and
motivated team are key to keep ischemia times to a minimum. In addition to
pharmacological approaches, machine perfusion seems promising to help circumvent
logistic problems and expand the donor pool in VCA.
PMID- 27495916
TI - The abdominal wall transplant as a sentinel skin graft.
AB - PURPOSE OF REVIEW: Abdominal wall transplantation is a technique used to achieve
abdominal closure after intestinal and multivisceral transplantation. This review
focuses on whether there are additional benefits for the skin component as an
immune-monitoring tool. RECENT FINDINGS: The largest series of abdominal wall
transplants has recently been published. Alongside the physiological advantage
gained in abdominal closure, the authors describe the immunological insight that
the skin component can provide and how this contributes to the management of
patients. The skin appears to develop a rash with early rejection, which
facilitates early systemic treatment before significant visceral rejection
occurs. It can also help in cases in which there is diagnostic doubt regarding
the cause of bowel dysfunction such as in instances of intestinal infection.
Despite the additional immunological burden of donor tissue, there appears to be
no requirement for increased immunosuppressive therapy. SUMMARY: The technical
and immunological feasibility of abdominal wall transplantation has now been
demonstrated by several centres. Skin transplanted as part of the abdominal wall
or as a separate vascularized sentinel skin flap may aid in the diagnosis of
rejection. This has the potential to improve graft survival and reduce
immunosuppressive morbidity.
PMID- 27495918
TI - Insurance claims related to opioid dependence have risen by 3200%, US study
finds.
PMID- 27495917
TI - Behavioral interventions to reduce inappropriate antibiotic prescribing: a
randomized pilot trial.
AB - BACKGROUND: Clinicians frequently prescribe antibiotics inappropriately for acute
respiratory infections (ARIs). Our objective was to test information technology
enabled behavioral interventions to reduce inappropriate antibiotic prescribing
for ARIs in a randomized controlled pilot test trial. METHODS: Primary care
clinicians were randomized in a 2 * 2 * 2 factorial experiment with 3
interventions: 1) Accountable Justifications; 2) Suggested Alternatives; and 3)
Peer Comparison. Beforehand, participants completed an educational module.
Measures included: rates of antibiotic prescribing for: non-antibiotic
appropriate ARI diagnoses, acute sinusitis/pharyngitis, all other
diagnoses/symptoms of respiratory infection, and all three ARI categories
combined. RESULTS: We examined 3,276 visits in the pre-intervention year and
3,099 in the intervention year. The antibiotic prescribing rate fell for non
antibiotic-appropriate ARIs (24.7 % in the pre-intervention year to 5.2 % in the
intervention year); sinusitis/pharyngitis (50.3 to 44.7 %); all other
diagnoses/symptoms of respiratory infection (40.2 to 25.3 %); and all categories
combined (38.7 to 24.2 %; all p < 0.001). There were no significant relationships
between any intervention and antibiotic prescribing for non-antibiotic
appropriate ARI diagnoses or sinusitis/pharyngitis. Suggested Alternatives was
associated with reduced antibiotic prescribing for other diagnoses or symptoms of
respiratory infection (odds ratio [OR], 0.62; 95 % confidence interval [CI], 0.44
0.89) and for all ARI categories combined (OR, 0.72; 95 % CI, 0.54-0.96). Peer
Comparison was associated with reduced prescribing for all ARI categories
combined (OR, 0.73; 95 % CI, 0.53-0.995). CONCLUSIONS: We observed large
reductions in antibiotic prescribing regardless of whether or not study
participants received an intervention, suggesting an overriding Hawthorne effect
or possibly clinician-to-clinician contamination. Low baseline inappropriate
prescribing may have led to floor effects. TRIAL REGISTRATION:
ClinicalTrials.gov: NCT01454960 .
PMID- 27495919
TI - Inactivation, lysis and degradation by-products of Saccharomyces cerevisiae by
electrooxidation using DSA.
AB - The yeast Saccharomyces cerevisiae, a microorganism with cell walls resistant to
many types of treatments, was chosen as a model to study electrochemical
disinfection process using dimensionally stable anodes (DSA). DSA electrodes with
nominal composition of Ti/RuO2TiO2 and Ti/RuO2TiO2IrO2 were evaluated in 0.05 mol
L-1 Na2SO4 containing yeast. The results showed inactivation about of 100 % of
the microorganisms at Ti/RuO2TiO2 by applying 20 and 60 mA cm-2 after 120 min of
electrolysis, while a complete inactivation at Ti/RuO2IrO2TiO2 electrode was
achieved after 180 min at 60 mA cm-2. When chloride ions were added in the
electrolyte solution, 100 % of the yeast was inactivated at 20 mA cm-2 after 120
min of electrolysis, independent of the anode used. In the absence of chloride,
the energy consumption (EC) was of 34.80 kWh m-3, at 20 mA cm-2 by using
Ti/RuO2TiO2 anode. Meanwhile, in the presence of chloride, EC was reduced,
requiring 30.24 and 30.99 kWh m-3 at 20 mA cm-2, for Ti/RuO2TiO2 and
Ti/RuO2IrO2TiO2 electrodes, respectively, The best performance for cell lysis was
obtained in the presence of chloride with EC of 88.80 kWh m-3 (Ti/RuO2TiO2) and
91.85 kWh m-3 (Ti/RuO2IrO2TiO2) to remove, respectively, 92 and 95 % of density
yeast. The results clearly showed that yeast, as a model adopted, was efficiently
inactivated and lysed by electrolysis disinfection using DSA-type electrodes.
PMID- 27495920
TI - Acute, chronic and biochemical effects of chlorothalonil on Agalychnis
callidryas, Isthmohyla pseudopuma and Smilisca baudinii tadpoles.
AB - Declines of amphibian populations have been a worldwide issue of concern for the
scientific community during the last several decades. Efforts are being carried
out to elucidate factors related to this phenomenon. Among these factors,
pathogens, climate change, and environmental pollution have been suggested as
possible causes. Regarding environmental pollutants, some pesticides are
persistent in the environment and capable of being transported long distances
from their release point. In Costa Rica, some pesticides have been detected in
protected areas, at locations where amphibian populations have declined.
Information about toxicity of pesticides used in Costa Rican agriculture to
amphibians is still scarce, particularly for native species.Toxicity tests with
chlorothalonil, a fungicide intensively used in Costa Rica, were carried out
exposing tadpoles of three Costa Rican native species: Agalychnis callidryas,
Isthmohyla pseudopuma, and Smilisca baudinii in order to evaluate acute and
chronic toxicity as well as the biomarkers cholinesterase activity (ChE),
glutathione-S transferase activity (GST), and lipid peroxidation (LPO).96-h LC50:
26.6 (18.9-35.8) MUg/L to A. callidryas, 25.5 (21.3-29.7) MUg/L to I pseudopuma
and 32.3 (26.3-39.7) MUg/L to S. baudinii were determined for chlorothalonil.
These three species of anurans are among the most sensitive to chlorothalonil
according to the literature. Besides, GST was induced in S. baudinii after
exposure to sub-lethal concentrations of chlorothalonil while evisceration
occurred in S. baudinii and A. callidryas tadpoles exposed to lethal
concentrations of the fungicide. Chronic exposure to sub-lethal concentrations
accelerated development in S. baudinii and caused lesions in tail of S. baudinii
and I. pseudopuma tadpoles. Our results demonstrate that chlorothalonil is highly
toxic to native amphibian species and that low concentrations can cause
biochemical responses related to phase II of biotransformation and effects on
development.
PMID- 27495921
TI - Properties of biochars from conventional and alternative feedstocks and their
suitability for metal immobilization in industrial soil.
AB - In contaminated soils, excessive concentrations of metals and their high mobility
pose a serious environmental risk. A suitable soil amendment can minimize the
negative effect of metals in soil. This study investigated the effect of
different biochars on metal (Cu, Pb, Zn) immobilization in industrial soil.
Biochars produced at 300 and 600 degrees C from conventional (MS, maize silage;
WP, wooden pellets) and alternative (SC, sewage sludge compost; DR, digestate
residue) feedstocks were used as soil amendments at a dosage of 10 % (w/w). The
type of feedstock and pyrolysis temperature affected the properties of the
biochars and their ability to immobilize metal in soil. Compared to production at
300 degrees C, all biochars produced at 600 degrees C had higher pH (6.2-10.7),
content of ash (7.2-69.0 %) and fixed carbon (21.1-56.7 %), but lower content of
volatile matter (9.7-37.2 %). All biochars except DR biochar had lower dissolved
organic carbon (DOC) content (1.4-2.3 g C/L) when made at 600 degrees C. Only MS
and SC biochars had higher cation exchange capacity (25.2 and 44.7 cmol/kg,
respectively) after charring at 600 degrees C. All biochars contained low
concentrations of Cd, Cu, Ni, Pb and Zn; Cd was volatilized to the greatest
extent during pyrolysis. Based on FTIR analysis and molar ratios of H/C and O/C,
biochars had a greater degree of carbonization and aromaticity after charring at
600 degrees C. The efficiency of the biochars in metal immobilization depended
mainly on their pH, ash content, and concentration of DOC. SC and DR biochars
were more effective for Cu and Zn immobilization than MS and WP biochars, which
makes them attractive options for large-scale soil amendment.
PMID- 27495923
TI - Erratum to: Geophysical, isotopic, and hydrogeochemical tools to identify
potential impacts on coastal groundwater resources from Urmia hypersaline Lake,
NW Iran.
PMID- 27495924
TI - Hypopigmented macules and papules following the lines of Blaschko: a novel
variant of Darier's disease.
PMID- 27495922
TI - Recovery of Lemna minor after exposure to sulfadimethoxine irradiated and non
irradiated in a solar simulator.
AB - Sulfonamides are the second most widely used group of veterinary antibiotics
which are often detected in the environment. They are eliminated from freshwaters
mainly through photochemical degradation. The toxicity of sulfadimethoxine (SDM)
was evaluated with the use of Lemna minor before and after 1- and 4-h irradiation
in a SunTest CPS+ solar simulator. Eight endpoints consisting of: number and
total area of fronds, fresh weight, chlorophylls a and b, carotenoids, activity
of catalase and guaiacol peroxidase, and protein content were determined. The
total frond area and chlorophyll b content were the most sensitive endpoints with
EC50 of 478 and 554 MUg L-1, respectively. The activity of guaiacol peroxidase
and catalase increased at SDM concentrations higher than 125 and 500 MUg L-1,
respectively. The SDM photodegradation rate for first order kinetics and the half
life were 0.259 h-1 and 2.67 h, respectively. The results show that the toxicity
of irradiated solutions was caused by SDM only, and the photoproducts appeared to
be either non-toxic or much less toxic to L. minor than the parent compound. To
study the recovery potential of L. minor, after 7 days exposure in SDM solutions,
the plants were transferred to fresh medium and incubated for the next 7 days. L.
minor has the ability to regenerate, but a 7-day recovery phase is not sufficient
for it to return to an optimal physiological state.
PMID- 27495925
TI - Biomechanism of chlorogenic acid complex mediated plasma free fatty acid
metabolism in rat liver.
AB - BACKGROUND: Plasma free fatty acids (FFA) are involved in blood lipid metabolism
as well as many health complications. The present study was conducted to evaluate
the potential role of chlorogenic acid complex from green coffee bean (CGA7) on
FFA metabolism in high fat diet fed rats. METHODS: Hyperlipidemia was induced in
Wistar rats using high-fat diet. The animals were given CGA7/orlistat
concurrently for 42 days. The parameters analysed during the study include plasma
and liver total cholesterol (TC), Triglycerides (TG) and FFA. AMPK activation in
the liver was analysed through ELISA. The multiple factors involved in AMPK
mediated FFA metabolism were analysed using western blotting. RESULTS: CGA7 (50,
100, 150 mg/kg BW) decreased triglycerides (TG) and FFA levels in plasma and
liver. CGA7 administration led to the activation of AMP-activated protein kinase
(AMPK) and a subsequent increase in the levels of carnitine palmitoyltransferase
1 (CPT-1). There was a decrease in acetyl-CoA carboxylase (ACC) activity as
evident by the increase in its phosphorylation level. CONCLUSION: Chlorogenic
acids improved the blood lipid metabolism in rats by alleviating the levels of
FFA and TG, modulating the multiple factors in liver through AMPK pathway. The
study concludes that CGA7 complex can be promoted as an active ingredient in
nutrition for obesity management.
PMID- 27495926
TI - Antimicrobial agents - optimising the ecological balance.
AB - BACKGROUND: There is no more challenging a group of pharmaceuticals than
antimicrobials. With the antibiotic era came great optimism as countless deaths
were prevented from what were previously fatal conditions. Although antimicrobial
resistance was quickly identified, the abundance of antibiotics entering the
market helped cement attitudes of arrogance as the "battle against pestilence
appeared won". Opposite emotions soon followed as many heralded the return of the
pre-antibiotic era, suggesting that the "antibiotic pipeline had dried up" and
that our existing armament would soon be rendered worthless. DISCUSSION: In
reality, humans overrate their ecological importance. For millions of years there
has been a balance between factors promoting bacterial survival and those
disturbing it. The first half century of the "antibiotic era" was characterised
by a cavalier attitude disturbing the natural balance; however, recent efforts
have been made through several mechanisms to respond and re-strengthen the
antimicrobial armament. Such mechanisms include a variety of incentives,
educational efforts and negotiations. Today, there are many more "man-made"
factors that will determine a new balance or state of ecological harmony.
CONCLUSION: Antibiotics are not a panacea nor will they ever be inutile. New
resistance mechanisms will be identified and new antibiotics will be discovered,
but most importantly, we must optimise our application of these extraordinary
"biological tools"; therein lays our greatest challenge - creating a society that
understands and respects the determinants of the effectiveness of antibiotics.
PMID- 27495928
TI - Evaluation of the perceptions and cosmetic satisfaction of breast cancer patients
undergoing totally implantable vascular access device (TIVAD) placement.
AB - PURPOSE: Totally implantable vascular access devices (TIVADs) are widely used to
administer chemotherapy to cancer patients. While great progress has been made
with respect to breast surgical reconstruction to take into account both
aesthetics and patients' perceptions of body integrity, these aspects have not
been considered with regard to the impact of TIVAD. In order to address this
practice gap, we have adapted our TIVAD implantation technique to improve
cosmetic results. The aim of this study was to assess breast cancer patients'
comfort level and aesthetic satisfaction with regard to TIVAD insertion. METHODS:
Patients with breast cancer admitted for chemotherapy at an outpatient clinic
completed a previously validated survey evaluating three main domains: symptoms
(pain, discomfort) related to the TIVAD itself in daily activity, information
received before and during the surgical procedure, and cosmetic aspects regarding
the port insertion site (scar, port, and catheter location). RESULTS: Between
September 2010 and June 2011, 232 patients were evaluated. Cosmetic satisfaction
with scar location was high (93.3 %). Information given to patients before and
during the procedure had a major impact on both symptom perception in daily
activity and on cosmetic satisfaction. CONCLUSIONS: Obtaining a more aesthetic
scar by placing the TIVAD in the deltopectoral groove contributed to a high rate
of cosmetic satisfaction. Furthermore, the relevance of information given to
patients before and/or during surgery had a major impact on symptom perception.
Therefore, we suggest including a pre-operative information session in the care
pathway.
PMID- 27495927
TI - It's not only what you say, it's also how you say it: communicating nipah virus
prevention messages during an outbreak in Bangladesh.
AB - BACKGROUND: During a fatal Nipah virus (NiV) outbreak in Bangladesh, residents
rejected biomedical explanations of NiV transmission and treatment and lost trust
in the public healthcare system. Field anthropologists developed and communicated
a prevention strategy to bridge the gap between the biomedical and local
explanation of the outbreak. METHODS: We explored residents' beliefs and
perceptions about the illness and care-seeking practices and explained prevention
messages following an interactive strategy with the aid of photos showed the
types of contact that can lead to NiV transmission from bats to humans by
drinking raw date palm sap and from person-to-person. RESULTS: The residents
initially believed that the outbreak was caused by supernatural forces and
continued drinking raw date palm sap despite messages from local health
authorities to stop. Participants in community meetings stated that the initial
messages did not explain that bats were the source of this virus. After our
intervention, participants responded that they now understood how NiV could be
transmitted and would abstain from raw sap consumption and maintain safer
behaviours while caring for patients. CONCLUSIONS: During outbreaks, one-way
behaviour change communication without meaningful causal explanations is unlikely
to be effective. Based on the cultural context, interactive communication
strategies in lay language with supporting evidence can make biomedical
prevention messages credible in affected communities, even among those who
initially invoke supernatural causal explanations.
PMID- 27495929
TI - Quantitative analysis of local-level resurgence.
AB - Resurgence is the recurrence of a previously reinforced and then extinguished
behavior induced by the extinction of another more recently reinforced behavior.
Resurgence provides insight into behavioral processes relevant to treatment
relapse of a range of problem behaviors. Resurgence is typically studied across
three phases: (1) reinforcement of a target response, (2) extinction of the
target and concurrent reinforcement of an alternative response, and (3)
extinction of the alternative response, resulting in the recurrence of target
responding. Because each phase typically occurs successively and spans multiple
sessions, extended time frames separate the training and resurgence of target
responding. This study assessed resurgence more dynamically and throughout
ongoing training in 6 pigeons. Baseline entailed 50-s trials of a free-operant
psychophysical procedure, resembling Phases 1 and 2 of typical resurgence
procedures. During the first 25 s, we reinforced target (left-key) responding but
not alternative (right-key) responding; contingencies reversed during the second
25 s. Target and alternative responding followed the baseline reinforcement
contingencies, with alternative responding replacing target responding across the
50 s. We observed resurgence of target responding during signaled and unsignaled
probes that extended trial durations an additional 100 s in extinction.
Furthermore, resurgence was greater and/or sooner when probes were signaled,
suggesting an important role of discriminating transitions to extinction in
resurgence. The data were well described by an extension of a stimulus-control
model of discrimination that assumes resurgence is the result of generalization
of obtained reinforcers across space and time. Therefore, the present findings
introduce novel methods and quantitative analyses for assessing behavioral
processes underlying resurgence.
PMID- 27495930
TI - Ultimate and proximate mechanisms of reciprocal altruism in rats.
AB - The reciprocal exchange of goods and services among social partners is a
conundrum in evolutionary biology because of its proneness to cheating, but also
the behavioral and cognitive mechanisms involved in such mutual cooperation are
hotly debated. Extreme viewpoints range from the assumption that, at the
proximate level, observed cases of "direct reciprocity" can be merely explained
by basic instrumental and Pavlovian association processes, to the other extreme
implying that "cultural factors" must be involved, as is often attributed to
reciprocal cooperation among humans. Here we argue that neither one nor the other
extreme conception is likely to explain proximate mechanisms underlying
reciprocal altruism in animals. In particular, we outline that Pavlovian
association processes are not sufficient to explain the documented reciprocal
cooperation among Norway rats, as has been recently argued.
PMID- 27495931
TI - Perceptual learning transfer in an appetitive Pavlovian task.
AB - In two experiments, rats were given intermixed or blocked preexposure to two
similar compound stimuli, AX and BX. Following preexposure, conditioning trials
took place in which AX (Experiment 1) or a novel compound stimulus NX (Experiment
2) was paired with a food-unconditioned stimulus in an appetitive Pavlovian
preparation. Animals that were given alternated preexposure showed lower
generalization from AX to BX (Experiment 1) and from NX to a new compound, ZX
(Experiment 2), than animals that were given blocked preexposure, a perceptual
learning and a perceptual learning transfer effect, respectively.
PMID- 27495932
TI - Intertrial unconditioned stimuli differentially impact trace conditioning.
AB - Three experiments assessed how appetitive conditioning in rats changes over the
duration of a trace conditioned stimulus (CS) when unsignaled unconditioned
stimuli (USs) are introduced into the intertrial interval. In Experiment 1, a
target US occurred at a fixed time either shortly before (embedded), shortly
after (trace), or at the same time (delay) as the offset of a 120-s CS. During
the CS, responding was most suppressed by intertrial USs in the trace group, less
so in the delay group, and least in the embedded group. Unreinforced probe trials
revealed a bell-shaped curve centered on the normal US arrival time during the
trace interval, suggesting that temporally specific learning occurred both with
and without intertrial USs. Experiments 2a and 2b confirmed that the bulk of the
trace CS became inhibitory when intertrial USs were scheduled, as measured by
summation and retardation tests, even though CS offset evoked a temporally
precise conditioned response. Thus, an inhibitory CS may give rise to new stimuli
specifically linked to its termination, which are excitatory. A modification to
the microstimulus temporal difference model is offered to account for the data.
PMID- 27495933
TI - Validity and reliability of ankle morphological measurements on computerized
tomography-synthesized planar radiographs.
AB - BACKGROUND: Clinical success of total ankle arthroplasty depends heavily on the
available information on the morphology of the bones, often obtained from
measurements on planar radiographs. The current study aimed to evaluate the intra
rater, inter-rater and inter-session reliability and the validity of radiograph
based measurements of ankle morphology, and to quantify the effects of examiner
experience on these measurements. METHODS: Twenty-four fresh frozen ankle
specimens were CT scanned, data of which were used to reconstruct 3D volumetric
bone models for synthesizing 2D radiographs. Two orthopaedic surgeons with
different levels of clinical experience identified twenty landmarks five times on
each of the synthesized sagittal and coronal radiographs and repeated the test on
a subsequent day within 5 days. The landmarks were used to calculate fourteen
morphological parameters. The two-way mixed-effects (ICC3,1), two-way random
effects (ICC2,k) and two-way random-effects (ICC3,k) models were used,
respectively, to assess the intra-rater, inter-rater and inter-session
reliability of measurements. The validity of the measurements for each examiner
was assessed by comparing them with gold standard values obtained from the 2D
radiographs projected from the 3D volumetric models using Pearson's correlation
analysis and Bland and Altman plots, and the differences were defined as the
measurement errors. RESULTS: Most of the morphological parameters were of good to
very good intra-rater, inter-session and inter-rater reliability for both
examiners (ICC > 0.61). Experience appeared to affect the inter-rater and inter
session reliability, the senior examiner showing greater inter-session ICC values
than the junior examiner. Most of the tibial parameters had moderate to excellent
correlations with the corresponding gold standard values but were underestimated
by both examiners, in contrast to most of the talar parameters that were
overestimated and had only poor to fair correlations. CONCLUSIONS: Most of the
morphological parameters of the ankle can be estimated from radiographs with good
to very good intra-rater, inter-session and inter-rater reliability, for both
clinically experienced and less experienced examiners. Clinical experience helped
increase the reliability of repeated evaluations after a longer interval, such as
in a follow-up assessment. It is suggested that critical clinical decisions based
on repeated morphology measurements should be made by more experienced surgeons
or after appropriate training.
PMID- 27495934
TI - Therapeutic evaluation of video-assisted thoracoscopic surgery versus open
thoracotomy for pediatric pulmonary hydatid disease.
AB - BACKGROUND: Hydatid disease is a severe and widespread human cestode infection,
and in children, the lung is the most commonly infected organ. In current
practice, the standard surgical procedure for the removal of pulmonary hydatid
cysts is thoracotomy; therefore, we evaluated the efficacy and safety of video
assisted thoracoscopic surgery (VATS) to treat pediatric pulmonary hydatid
disease. To our knowledge, this is the first and large sample comparative study
of VATS and thoracotomy for pediatric pulmonary hydatid disease. METHODS: In this
study, we retrospectively reviewed 44 (61.1 %) pediatric patients who underwent
VATS, and 28 (38.9 %) pediatric patients who underwent conventional thoracotomy
from January 2005 to June 2012. Perioperative data, including basic
characteristics of patients, the length of hospital stay, intraoperative blood
loss, thoracic intubation indwelling time, and complications were compared
between VATS and thoracotomy in 72 children with pulmonary hydatid disease.
RESULTS: VATS was found to be a safe technique for the treatment of pediatric
pulmonary hydatid disease, with zero intraoperative deaths. In the VATS and
thoracotomy groups, the hospital stay durations were 10.50 +/- 1.20 days and
17.30 +/- 2.75 days, respectively, and occurrence rates of complications were 9.1
% (4/44) and 17.9 % (5/28), respectively. The hospital stays were shorter and the
hospitalization costs was reduced for the patients who underwent VATS compared
with conventional thoracotomy (P = 0.001). Although no statistically significant
difference in the recurrence rates (P = 0.958) and complication incidence (P =
0.273) between the two surgical groups was observed, less intraoperative
bleeding, shorter thoracic intubation indwelling time and reduced postoperative
pain were observed in the patients who underwent VATS (P = 0.001). CONCLUSION:
Our study demonstrates the feasibility and safety of VATS for pediatric pulmonary
hydatid disease treatment, providing a practice-changing concept for the
treatment of this disease in the community. VATS can be a promising therapeutic
tool, by overcoming many of the drawbacks of thoracotomy, and can be used as an
alternative to thoracotomy for selected pediatric patients.
PMID- 27495935
TI - Social Modulation or Hormonal Causation? Linkages of Testosterone with Sexual
Activity and Relationship Quality in a Nationally Representative Longitudinal
Sample of Older Adults.
AB - This study used population-representative longitudinal data from the 2005-2006
and 2010-2011 waves of the National Social Life, Health and Aging Project-a
probability sample of US adults aged 57-85 at baseline (N = 650 women and 620
men)-to examine the causal direction in linkages of endogenous testosterone (T)
with sexual activity and relationship quality. For both genders, our
autoregressive effects indicated a large amount of temporal stability, not just
in individual-level attributes (T, masturbation) but also dyadic ones (partnered
sex, relationship quality)-indicating that a need for more nuanced theories of
relational processes. Cross-lagged results suggested gender-specific effects
generally more consistent with sexual or relational modulation of T than with
hormonal causation. Specifically, men's findings indicated their T might be
elevated by their sexual (masturbatory) activity but not vice versa, although
androgen levels did lower men's subsequent relationship quality. Women's T, in
contrast, was negatively influenced not just by their higher relationship quality
but also by their more frequent partnered sex-perhaps reflecting a changing
function of sexual activity in late life.
PMID- 27495936
TI - Opt-in method is vital for data sharing.
PMID- 27495937
TI - Rapid generation of functional hepatocyte-like cells from human adipose-derived
stem cells.
AB - BACKGROUND: Liver disease is a major cause of death worldwide. Orthotropic liver
transplantation (OLT) represents the only effective treatment for patients with
liver failure, but the increasing demand for organs is unfortunately so great
that its application is limited. Hepatocyte transplantation is a promising
alternative to OLT for the treatment of some liver-based metabolic disorders or
acute liver failure. Unfortunately, the lack of donor livers also makes it
difficult to obtain enough viable hepatocytes for hepatocyte-based therapies.
Currently, a fundamental solution to this key problem is still lacking. Here we
show a novel non-transgenic protocol that facilitates the rapid generation of
functional induced hepatocytes (iHeps) from human adipose-derived stem cells
(hADSCs), providing a source of available cells for autologous hepatocytes to
treat liver disease. METHODS: We used collagenase digestion to isolate hADSCs.
The surface marker was detected by flow cytometry. The multipotential
differentiation potency was detected by induction into adipocytes, osteocytes,
and chondrocytes. Passage 3-7 hADSCs were induced into iHeps using an induction
culture system composed of small molecule compounds and cell factors. RESULTS:
Primary cultured hADSCs presented a fusiform or polygon appearance that became
fibroblast-like after passage 3. More than 95 % of the cells expressed the
mesenchymal cell markers CD29, CD44, CD166, CD105, and CD90. hADSCs possessed
multipotential differentiation towards adipocytes, osteocytes, and chondrocytes.
We rapidly induced hADSCs into iHeps within 10 days in vitro; the cellular
morphology changed from fusiform to close-connected cubiform, which was similar
to hepatocytes. After induction, most of the iHeps co-expressed albumin and alpha
1 antitrypsin; they also expressed mature hepatocyte special genes and achieved
the basic functions of hepatocyte. Moreover, iHep transplantation could improve
the liver function of acute liver-injured NPG mice and prolong life. CONCLUSIONS:
We isolated highly purified hADSCs and rapidly induced them into functional
hepatocyte-like cells within 10 days. These results provide a source of available
cells for autologous hepatocytes to treat liver disease.
PMID- 27495939
TI - Intimacy and Smartphone Multitasking-A New Oxymoron?
AB - This study investigated the relationship between smartphone multitasking and
romantic intimacy. Participants currently in a romantic relationship (N = 128; 98
women; M age = 26.7 years, SD = 4.3) filled out two sets of questionnaires: The
Emotional Intimacy Scale, measuring romantic intimacy, and the mobile phone
interference in life scale, measuring multitasking on a smartphone. Participants
filled out each questionnaire twice, once in relation to themselves and once in
relation to their partner (for the partner questionnaire, statements were altered
from the first person to the third person singular, he/she instead of I). Results
suggested that only the partners' smartphone multitasking scores were negatively
related to ratings of romantic intimacy, whereas participants' own smartphone
multitasking scores were not related to ratings of romantic intimacy. These
results can be explained by the actor-observer asymmetry, suggesting that
participants attributed their multitasking behaviors to situations, but
attributed their partners multitasking behaviors to behavior patterns or
intentionality. This research suggests that smartphone multitasking has a
negative association with face-to-face interactions. People should attend to the
costs of smartphone use during face-to-face interactions.
PMID- 27495938
TI - Tandem Delivery of Multiple Therapeutic Genes Using Umbilical Cord Blood Cells
Improves Symptomatic Outcomes in ALS.
AB - Current treatment options of chronic, progressive degenerative neuropsychiatric
conditions offer only marginal efficacy, and there is no therapy which arrests or
even reverses these diseases. Interest in genetic engineering and cell-based
approaches have constantly been increasing, although most of them so far proved
to be fruitless or at best provided very slight clinical benefit. In the light of
the highly complex patho-mechanisms of these maladies, the failure of drugs aimed
at targeting single molecules is not surprising. In order to improve their
effectiveness, the role of a unique triple-combination gene therapy was
investigated in this study. Intravenous injection of human umbilical cord blood
mononuclear cell (hUCBMC) cotransduced with adenoviral vectors expressing
vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor
(GDNF), and neural cell adhesion molecule (NCAM) resulted in prominent increase
of life span and performance in behavioral tests in amyotrophic lateral sclerosis
(ALS). Expression of the recombinant genes in hUCBMCs was confirmed as soon as 5
days after transduction by RT-PCR, and cells were detectable for as long as 1
month after grafting in lumbar spinal cord by immunofluorescent staining.
Xenotransplantation of cells into mice blood without any immunosuppression
demonstrated a high level of hUCBMCs homing and survivability in the central
nervous system (CNS), most conspicuously in the spinal cord, but not in the
spleen or liver. This study confirms an increased addressed homing and notable
survivability of triple-transfected cells in lumbar spinal cord, yielding a
remarkably enhanced therapeutic potential of hUCBMCs overexpressing neurotrophic
factors.
PMID- 27495940
TI - Detecting a novel Eriocheir sinensis reovirus by reverse transcription loop
mediated isothermal amplification assay.
AB - : The novel Eriocheir sinensis reovirus (EsRV) is a pathogen that causes severe
disease and high mortality rates in cultivated crabs. Here, we established a
highly sensitive and specific rapid reverse transcription loop-mediated
isothermal amplification (RT-LAMP) assay that was cheaper and more suitable for
field applications in crab aquaculture than those of traditional reverse
transcription-polymerase chain reaction (RT-PCR) analysis. The amplification was
completed within 45 min under isothermal conditions at 65 degrees C. The RT-LAMP
test for EsRV had a detection limit of 15 pg, and sensitivity was 100 times
greater than that of conventional RT-PCR. The LAMP primers for EsRV were not
amplified by other pathogen strains, indicating good specificity. In addition to
detection by electrophoresis, RT-LAMP results were detectable by visual
observations of reaction tube turbidity, and calcein was added to visually detect
the amplification products. These results indicate that this highly convenient,
rapid and sensitive RT-LAMP assay can be used to detect EsRV-infected aquatic
organisms. SIGNIFICANCE AND IMPACT OF THE STUDY: Tremor disease (TD) is one of
the most serious diseases of Eriocheir sinensis. A novel E. sinensis reovirus
(EsRV) was identified from E. sinensis afflicted with TD and caused high
mortality. We developed a reverse transcription loop-mediated isothermal
amplification assay with high specificity, sensitivity and rapidity to detect
EsRV, which can be used to diagnose aquatic animal diseases, particularly where
expensive diagnostic instruments are not available.
PMID- 27495941
TI - Role of Glycosyltransferases in Pollen Wall Primexine Formation and Exine
Patterning.
AB - The pollen cell wall is important for protection of male sperm from physical
stresses and consists of an inner gametophyte-derived intine layer and a
sporophyte-derived exine layer. The polymeric constituents of the robust exine
are termed sporopollenin. The mechanisms by which sporopollenin is anchored onto
microspores and polymerized in specific patterns are unknown, but the primexine,
a transient cell wall matrix formed on the surface of microspores at the late
tetrad stage, is hypothesized to play a key role. Arabidopsis (Arabidopsis
thaliana) spongy (spg) and uneven pattern of exine (upex) mutants exhibit
defective and irregular exine patterns. SPG2 (synonymous with IRREGULAR XYLEM9
LIKE [IRX9L]) encodes a family GT43 glycosyltransferase involved in xylan
backbone biosynthesis, while UPEX1 encodes a family GT31 glycosyltransferase
likely involved in galactosylation of arabinogalactan proteins. Imaging of
developing irx9l microspores showed that the earliest detectable defect was in
primexine formation. Furthermore, wild-type microspores contained primexine
localized epitopes indicative of the presence of xylan, but these were absent in
irx9l These data, together with the spg phenotype of a mutant in IRX14L, which
also plays a role in xylan backbone elongation, indicate the presence of xylan in
pollen wall primexine, which plays a role in exine patterning on the microspore
surface. We observed an aberrant primexine and irregular patterns of incipient
sporopollenin deposition in upex1, suggesting that primexine-localized
arabinogalactan proteins could play roles in sporopollenin adhesion and
patterning early in microspore wall development. Our data provide new insights
into the biochemical and functional properties of the primexine component of the
microspore cell wall.
PMID- 27495942
TI - Differences in calcification and osteogenic potential of herniated discs
according to the severity of degeneration based on Pfirrmann grade: a cross
sectional study.
AB - BACKGROUND: Herniated discs may exhibit calcification, and calcified discs may
complicate surgical treatment. However, the osteogenic potential and expression
of osteogenic markers in degenerative discs of different degenerative grades are
still unclear. Our purposes are to study the differences in calcification rate
and osteogenic potential of herniated discs according to different degenerative
grades. METHODS: Fifty-eight lumbar intervertebral discs were removed from 41
patients. After grading according to the Pfirrmann scale, calcification was
analyzed by micro computed tomography (MU-CT), and expression of osteogenic
markers was analyzed by immunohistochemistry and real-time quantitative
polymerase chain reaction (qPCR). Data from MU-CT scans were compared with the
Kruskal-Wallis test. The Mann-Whitney test was applied to compare data between
any two groups. Differences in osteogenic mRNA expression in different regions of
the removed discs (posterior vs. anterior) were analyzed by paired t tests.
Differences in the posterior portion of removed discs of different Pfirrmann
grades were analyzed by one-way analysis of variance (ANOVA), and comparisons of
data between discs of any two grades were completed with least significant
difference (LSD) tests. RESULTS: Significant differences in calcification
according to MU-CT scanning were observed between discs of different degenerative
grades. Nearly half of the discs of Pfirrmann grade V showed the highest degree
of calcification compared to Pfirrman grade II discs. Bone morphogenetic protein
(BMP)-2, Osterix, and Osteocalcin were detected histologically in discs of
Pfirrmann grades III-V. Alkaline phosphatase (ALP) expression was observed in
discs showing evidence of calcification. The qPCR analysis showed that BMP-2,
Osterix, and Osteocalcin were expressed in most degenerated discs. We also
observed greater expression of these osteogenic markers in the posterior portion
of removed discs than in the anterior portion. CONCLUSIONS: The osteogenic
potential of degenerated intervertebral discs appears to increase with the
severity of degeneration and to be greater in the tissue near the spinal canal
than in tissue in the inner portion of the disc.
PMID- 27495943
TI - Projectile propagation of dexamethasone implant in air- and balanced salt
solution-filled vitrectomized eyes.
PMID- 27495944
TI - Correlation of Adrenomedullin Concentrations with Knee Osteoarthritis Grade.
AB - BACKGROUND Adrenomedullin, a recently identified myokine, has an anti
inflammatory effect. Therefore, we aimed to assess the correlation of
adrenomedullin concentrations with the presence and grade of severity of knee
osteoarthritis (OA). MATERIAL AND METHODS We recruited 187 knee OA patients and
109 healthy subjects. The severity of OA was evaluated using the Kellgren
Lawrence grading system. RESULTS Compared with the control group, the knee OA
group revealed markedly higher adrenomedullin concentrations. Serum and synovial
fluid (SF) adrenomedullin concentrations increased with increased KL grades.
CONCLUSIONS Serum and SF adrenomedullin concentrations show a correlation with
the severity of knee OA.
PMID- 27495945
TI - Bone shape difference between control and osteochondral defect groups of the
ankle joint.
AB - OBJECTIVE: The etiology of osteochondral defects (OCDs), for which the ankle
(talocrural) joint is one of the common sites, is not yet fully understood. In
this study, we hypothesized that bone shape plays a role in development of OCDs.
Therefore, we quantitatively compared the morphology of the talus and the distal
tibia between an OCD group and a control group. METHODS: The shape variations of
the talus and distal tibia were described separately by constructing two
statistical shape models (SSMs) based on the segmentation of the bones from ankle
computed tomography (CT) scans obtained from control (i.e., 35 CT scans) and OCD
(i.e., 37 CT scans) groups. The first five modes of shape variation for the SSM
corresponding to each bone were statistically compared between control and OCD
groups using an analysis of variance (ANOVA) corrected with the Bonferroni for
multiple comparisons. RESULTS: The first five modes of variation in the SSMs
respectively represented 49% and 40% of the total variance of talus and tibia.
Less than 5% of the variance per mode was described by the higher modes. Mode 5
of the talus (P = 0.004) primarily describing changes in the vertical neck angle
and Mode 1 of the tibia (P < 0.0001) representing variations at the medial
malleolus, showed statistically significant difference between the control and
OCD groups. CONCLUSION: Shape differences exist between control and OCD groups.
This indicates that a geometry modulated biomechanical behavior of the talocrural
joint may be a risk factor for OCD.
PMID- 27495946
TI - Effect of sample treatment on biomechanical properties of insect cuticle.
AB - Experimental limitations often prevent to perform biomechanical measurements on
fresh arthropod cuticle samples. Hence, in many cases short- or long-term storage
of samples is required. So far, it is not known whether any of the standard lab
techniques commonly used to fix or store insect cuticle samples in any way
affects the biomechanical properties of the respective samples. In this paper we
systematically address this question for the first time, with a focus on
practical, easily accessible and common lab-methods including storage in water,
ethanol, glutaraldehyde, freezing and desiccation. We performed a comprehensive
and sensitive non-destructive Dynamic Mechanical Analysis (DMA) on locust hind
leg tibiae using a three-point-bending setup. Our results show that from all
tested treatments, freezing samples at -20 degrees C was the best option to
maintain the original values for Young's modulus and damping properties of insect
cuticle. In addition, our results indicate that the damping properties of locust
hind legs might be mechanically optimized in respect to the jumping and kicking
direction.
PMID- 27495947
TI - Venous thromboembolism in centenarians: Findings from the RIETE registry.
AB - BACKGROUND: The balance between the efficacy and safety of anticoagulant therapy
in patients aged >=100years receiving anticoagulant therapy for venous
thromboembolism (VTE) is uncertain. METHODS: We used data from the RIETE
(Registro Informatizado Enfermedad TromboEmbolica) database to assess the rate of
VTE recurrences, bleeding events, and mortality appearing during the course of
anticoagulant therapy in VTE patients aged >=100years. RESULTS: Of 61,173
patients enrolled in RIETE as of January 2016, 47 (0.08%) were aged >=100years.
Of these, 10 (21%) were men, 21 (45%) presented with pulmonary embolism (PE), and
26 with deep vein thrombosis alone. Overall, 35 patients (74%) had severe renal
insufficiency, 14 (30%) chronic heart failure, 30 (64%) anemia, 16 (34%) were
taking antiplatelets, and 6 (13%) corticosteroids or non-steroidal anti
inflammatory drugs. Most patients (95%) were treated initially with low-molecular
weight heparin (LMWH) (mean daily dose, 168+/-42IU/kg). Then, 14 (30%) switched
to vitamin K antagonists and 29 (62%) kept receiving long-term LMWH therapy
(mean, 148+/-51IU/kg/day). During the course of anticoagulant therapy (mean
duration, 139days), mortality was high (15/47; 32%). Two patients died of PE
(initial PE one, recurrent PE one) and 5 (11%) had minor bleeding, but no major
bleeding was reported. CONCLUSIONS: Among patients with acute VTE aged
>=100years, the risk of VTE recurrences during the course of anticoagulation
outweighed the risk of bleeding. Our data suggest the use of standard
anticoagulant therapy in this patient population, even if they have severe renal
insufficiency.
PMID- 27495948
TI - Chronic pruritic, hyperkeratotic eruption on the feet of a patient with end-stage
renal disease.
PMID- 27495949
TI - MEDical wards Invasive Candidiasis ALgorithms (MEDICAL):Consensus proposal for
management.
AB - INTRODUCTION: A majority of invasive Candida infections occur in medical wards;
however, evidence for management in this setting is scarce and based primarily on
the intensive care or surgical setting. On behalf of the Italian Society for Anti
Infective Therapy (SITA) and the Italian Federation of Associations of Hospital
Doctors on Internal Medicine (FADOI), the MEDICAL group produced practical
management algorithms for patients in internal medicine wards. METHODS: The
MEDICAL group panel, composed of 30 members from internal medicine, infectious
disease, clinical pharmacology, clinical microbiology and clinical epidemiology,
provided expert opinion through the RAND/UCLA method. RESULTS: Seven clinical
scenarios were constructed based on clinical severity and probability of invasive
candidiasis. For each scenario, the appropriateness of 63 different diagnostic,
imaging, management, or therapeutic procedures was determined in two Delphi
rounds. The necessity for performing each appropriate procedure, was then
determined in a third Delphi round. Results were summarized in algorithms.
DISCUSSION: The proposed algorithms provide internal medicine physicians and
managers with an easy to interpret tool that is exhaustive, clear and suitable
for adaption to individual local settings. Attention was paid to individual
patient management and resource allocation.
PMID- 27495950
TI - Visual consequences of electronic reader use: a pilot study.
AB - BACKGROUND: With the increasing prevalence of electronic readers (e-readers) for
vocational and professional uses, it is important to discover if there are visual
consequences in the use of these products. There are no studies in the literature
quantifying the incidence or severity of eyestrain, nor are there clinical
characteristics that may predispose to these symptoms with e-reader use. PURPOSE:
The primary objective of this pilot study was to assess the degree of eyestrain
associated with e-reader use compared to traditional paper format. The secondary
outcomes of this study were to assess the rate of eyestrain associated with e
reader use and identify any clinical characteristics that may be associated with
the development of eyestrain. METHODS: Forty-four students were randomly assigned
to study (e-reader iPAD) and control (print) groups. Participant posture,
luminosity of the room, and reading distance from reading device were measured
during a 1-h session for both groups. At the end of the session, questionnaires
were administered to determine symptoms. RESULTS: Significantly higher rates of
eyestrain (p = 0.008) and irritation (p = 0.011) were found among the iPAD study
group as compared to the print 'control' group. The study group was also 4.9
times more likely to report severe eyestrain (95 % CI [1.4, 16.9]). No clinical
characteristics predisposing to eyestrain could be identified. CONCLUSIONS: These
findings conclude that reading on e-readers may induce increased levels of
irritation and eyestrain. Predisposing factors, etiology, and potential remedial
interventions remain to be determined.
PMID- 27495951
TI - Histopathological and ophthalmoscopic evaluation of apocynin on experimental
proliferative vitreoretinopathy in rabbit eyes.
AB - The aim of the current study was to evaluate the effect of apocynin (APO) on the
development of proliferative vitreoretinopathy (PVR). New Zealand-type male
rabbits were randomly grouped into three as follows: (1) Sham group rabbits which
were applied intraperitoneal (i.p.) vehicle without PVR; (2) PVR group rabbits
where PVR was created and an i.p. vehicle was administered for 21 successive
days; (3) PVR + APO group rabbits where PVR was created and i.p. APO was
administered for 21 successive days. Fundus examination was conducted with an
indirect ophthalmoscope before starting the experiments and at each visit
afterwards. At the end of the work, the rabbits were sacrificed under high-dose
anesthesia and then eye tissues were taken for histopathological analyses. In the
PVR + APO group, histopathologic and ophthalmoscopic examination revealed
significant decrease in PVR formation. As the result, it has been observed that
APO at least partially inhibits PVR formation.
PMID- 27495952
TI - Surgical outcomes of patients with iridocorneal endothelial syndrome: a case
series.
AB - The purpose of this study is to report the intermediate-term surgical outcomes of
patients with iridocorneal endothelial syndrome-related glaucoma. The medical
records of four patients (five eyes) surgery (Ahmed glaucoma valve implantation
surgery and EX-PRESS mini shunt) were retrospectively reviewed. Median follow-up
after glaucoma surgery was 24 (15-36) months. The preoperative intraocular
pressure was significantly reduced from a median of 33 (22.5-36) mmHg on a median
of 4 (4-5) glaucoma medications to a median of 12 (10.5-14.5) mmHg on a median of
2 (0-2) medications at last follow-up after surgery (p = 0.043 for IOP and p =
0.042 for glaucoma medications). Median preoperative visual acuity [0.016 (0.008
0.1)] did not change significantly when compared to median visual acuity at last
follow-up [0.016 (0.004-0.5)] (p = 0.59). Intraocular pressure control in
patients with iridocorneal endothelial syndrome is challenging and may require
multiple operations and revisions. Some modifications during glaucoma drainage
implant surgery and use of EX-PRESS mini shunt in certain cases could offer an
advantage in these patients.
PMID- 27495953
TI - Atrazine alters expression of reproductive and stress genes in the developing
hypothalamus of the snapping turtle, Chelydra serpentina.
AB - Atrazine is an herbicide used to control broadleaf grasses and a suspected
endocrine disrupting chemical. Snapping turtles lay eggs between late May and
early June, which could lead to atrazine exposure via field runoff. Our goal was
to determine whether a single exposure to 2ppb or 40ppb atrazine during
embryogenesis could induce short- and long-term changes in gene expression within
the hypothalamus of snapping turtles. We treated eggs with atrazine following sex
determination and measured gene expression within the hypothalamus. We selected
genes a priori for their role in the hypothalamus-pituitary-gonad or the
hypothalamus-pituitary-adrenal axes of the endocrine system. We did not identify
any changes in gene expression 24-h after treatment. However, at hatching AR,
Kiss1R, and POMC expression was upregulated in both sexes, while expression of
CYP19A1 and PDYN was increased in females. Six months after hatching, CYP19A1 and
PRLH expression was increased in animals treated with 2ppb atrazine. Our study
shows persistent changes in hypothalamic gene expression due to low-dose
embryonic exposure to the herbicide atrazine with significant effects in both the
HPG and HPA axes. Effects reported here appear to be conserved among vertebrates.
PMID- 27495954
TI - Propofol reduced myocardial contraction of vertebrates partly by mediating the
cyclic AMP-dependent protein kinase phosphorylation pathway.
AB - Propofol inhibits myocardial contraction in a dose dependent manner. The present
study is designed to examine the effect of propofol on PKA mediated myocardial
contraction in the absence of adrenoreceptor agonist. The contraction of isolated
rat heart was measured in the presence or absence of PKA inhibitor H89 or
propofol, using a pressure transducer. The levels of cAMP and PKA kinase activity
were detected by ELISA. The mRNA and total protein or phosphorylation level of
PKA and downstream proteins were tested in the presence or absence of PKA
inhibitor H89 or propofol, using RT-PCR, QPCR and western blotting. The
phosphorylation level of PKA was examined thoroughly using immunofluorescence and
PKA activity non-radioactive detection kit. Propofol induced a dose-dependent
negative contractile response on the rat heart. The inhibitory effect of high
concentration propofol (50MUM) with 45% decease of control could be partly
reversed by the PKA inhibitor H89 (10MUM) and the depressant effect of propofol
decreased from 45% to 10%. PKA kinase activity was inhibited by propofol in a
dose-dependent manner. Propofol also induced a decrease in phosphorylation of
PKA, which was also inhibited by H89, but did not alter the production of cAMP
and the mRNA levels of PKA. The downstream proteins of PKA, PLN and RyR2 were
phosphorylated to a lesser extent with propofol or H89 than control. These
results demonstrated that propofol induced a negative myocardial contractile
response partly by mediating the PKA phosphorylation pathway.
PMID- 27495955
TI - Effect of fermented red ginseng on cytochrome P450 and P-glycoprotein activity in
healthy subjects, as evaluated using the cocktail approach.
AB - AIMS: We assessed the drug interaction profile of fermented red ginseng with
respect to the activity of major cytochrome (CYP) P450 enzymes and of a drug
transporter protein, P-glycoprotein (P-gp), in healthy volunteers. METHODS: This
study was an open-label crossover study. The CYP probe cocktail drugs caffeine,
losartan, dextromethorphan, omeprazole, midazolam and fexofenadine were
administered before and after 2 weeks of fermented red ginseng administration.
Plasma samples were collected, and tolerability was assessed. Pharmacokinetic
parameters were calculated, and the 90% confidence intervals (CIs) of the
geometric mean ratios of the parameters were determined from logarithmically
transformed data. Values were compared between before and after fermented red
ginseng administration using analysis of variance (anova). RESULTS: Fifteen
healthy male subjects were evaluated, none of whom were genetically defined as a
poor CYP2C9, CYP2C19 or CYP2D6 metabolizer based on genotyping. Before and after
fermented red ginseng administration, the geometric least-square mean metabolic
ratio (90% CI) was 0.901 (0.830-0.979) for caffeine (CYP1A2) to paraxanthine,
0.774 (0.720-0.831) for losartan (CYP2C9) to EXP3174, 1.052 (0.925-1.197) for
omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.150 (0.860-1.538) for
dextromethorphan (CYP2D6) to dextrorphan, and 0.816 (0.673-0.990) for midazolam
(CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the
curve of the last sampling time (AUClast ) for fexofenadine (P-gp) was 1.322
(1.112-1.571). CONCLUSION: No significantly different drug interactions were
observed between fermented red ginseng and the CYP probe substrates following the
two-week administration of concentrated fermented red ginseng. However, the
inhibition of P-gp was significantly different between fermented red ginseng and
the CYP probe substrates. The use of fermented red ginseng requires close
attention due to the potential for increased systemic exposure when it is used in
combination with P-gp substrate drugs.
PMID- 27495957
TI - Musculoskeletal imaging: What's new in 2016?
PMID- 27495956
TI - Towards Improving the Transfer of Care of Kidney Transplant Recipients.
AB - Kidney transplant recipients require specialized medical care and may be at risk
for adverse health outcomes when their care is transferred. This document
provides opinion-based recommendations to facilitate safe and efficient transfers
of care for kidney transplant recipients including minimizing the risk of
rejection, avoidance of medication errors, ensuring patient access to
immunosuppressant medications, avoidance of lapses in health insurance coverage,
and communication of risks of donor disease transmission. The document summarizes
information to be included in a medical transfer document and includes
suggestions to help the patient establish an optimal therapeutic relationship
with their new transplant care team. The document is intended as a starting point
towards standardization of transfers of care involving kidney transplant
recipients.
PMID- 27495958
TI - Out-of-hospital unexpected delivery.
PMID- 27495959
TI - Comparison of the visualisation of the subclavian and axillary veins: An
ultrasound study in healthy volunteers.
AB - OBJECTIVE: To compare the area of the lumen of the axillary and subclavian veins
using ultrasound (US) in 50 healthy volunteers. METHODS: Using an ultrasound
device, depth, area, short axis vein length and long axis vein, vein-artery and
vein-pleura distances were measured for axillary and subclavian approaches.
RESULTS: The mean cross-sectional area of the axillary vein was greater than the
mean cross-sectional area of the subclavian vein (327+/-89 mm2 versus 124+/-46
mm2, P<0.001). Both the mean transverse (10+/-2mm versus 9+/-2mm) and
longitudinal axes (39+/-8mm versus 17+/-7mm) of the axillary vein were greater
than those of subclavian vein (P<0.01, P<0.001, respectively). The depths of the
axillary and subclavian veins were similar (21+/-6mm versus 20+/-6mm, P=0.43).
The axillary and subclavian arteries were visualised in 3 and 45 volunteers,
respectively (P<0.001). The pleura was seen in 25 and 37 volunteers with the
axillary and subclavian approaches, respectively (P=0.01). The distance between
the pleura and the subclavian vein was smaller (6+/-2mm versus 8+/-3mm, P<0.04).
CONCLUSION: The present US study shows that visualisation of the axillary vein
under US is greater than that for the subclavian vein, mainly due to a better
alignment with the long axis of the axillary vein leading to a greater cross
sectional area of the axillary vein. TRIAL REGISTER NUMBER: NCT01647815.
PMID- 27495960
TI - Optimal Head Rotation for IJV Cannulation: One Size Does Not Fit All.
PMID- 27495961
TI - Outcome After General Anesthesia Versus Monitored Anesthesia Care in Transfemoral
Transcatheter Aortic Valve Replacement.
AB - OBJECTIVE: To evaluate outcomes of monitored anesthesia care (MAC) compared with
general anesthesia (GA) in patients undergoing transfemoral transcatheter aortic
valve replacement (TAVR). DESIGN: Secondary analysis from the observational and
prospective OBSERVANT (OBservational Study of Effectiveness of avR-taVi
procedures for severe Aortic steNosis Treatment) study. SETTING: Multicenter
study, including Italian hospitals performing TAVR interventions. PARTICIPANTS:
One thousand four hundred ninety-four patients with severe and symptomatic aortic
stenosis. INTERVENTIONS: Transfemoral TAVR under general or local anesthesia.
MEASUREMENTS AND MAIN RESULTS: A propensity score procedure was applied, and 310
pairs were matched with similar baseline characteristics (EuroSCORE II: local
anesthesia 6.6+/-5.9% v general anesthesia 7.0+/-7.7%, p = 0.430). MAC was
associated with similar 30-day mortality compared with GA (3.9% v 4.8%, p =
0.564). TAVR was performed under MAC without any increased risk of other adverse
events. The risk of paravalvular regurgitation>=mild was similar between the
study groups (MAC 49.5% v general anesthesia 57.0%, p = 0.858). Two patients
receiving on MAC had severe paravalvular regurgitation, whereas this complication
was not observed after GA. Permanent pacemaker implantation was 19.1% in the MAC
group v 14.8% in the GA group (p = 0.168). Mean intensive care unit stay was 3.5
days for the GA group v 2.9 days for the MAC group (p = 0.086). A similar 3-year
survival rate was observed (MAC 69.4% v GA 69.9%, p = 0.966). CONCLUSIONS:
Transfemoral TAVR can be performed under MAC with similar immediate and late
outcomes as compared with GA. A possible risk of severe paravalvular
regurgitation and pacemaker implantation with TAVR under MAC requires further
investigation.
PMID- 27495962
TI - Grading Aortic Stenosis With Mean Gradient and Aortic Valve Area: A Comparison
Between Preoperative Transthoracic and Precardiopulmonary Bypass Transesophageal
Echocardiography.
AB - OBJECTIVE: The authors hypothesized that average precardiopulmonary bypass (pre
CPB) transesophageal echocardiographic (TEE) mean gradient (PGm) and aortic valve
area (AVA) values would be significantly different from preoperative
transthoracic (TTE) values in the same patients and that these changes would
affect pre-CPB TEE grading of aortic stenosis (AS). DESIGN: Retrospective,
observational design. SETTING: Single university hospital. PARTICIPANTS: The
study comprised 92 patients who underwent aortic valve replacement with or
without coronary artery bypass grafting between 2000 and 2012 at Duke University
Hospital and who had PGm and AVA values recorded in both pre-CPB TEE and
preoperative TTE reporting databases. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: PGm with pre-CPB TEE was lower by 6.6 mmHg (95% confidence interval,
4.0 to -9.3 mmHg; p<0.001), whereas AVA was higher by 0.10 cm(2) (95% confidence
interval, 0.04 to 0.15 cm(2); p<0.001), compared with preoperative TTE values.
When using PGm, pre-CPB TEE generated an AS severity 1 grade lower 39.1% of the
time and revealed no difference 55.4% of the time compared to preoperative TTE.
When using AVA by continuity, pre-CPB TEE generated an AS severity 1 grade lower
14.1% of the time and revealed no difference 81.5% of the time compared to
preoperative TTE. When using either PGm or AVA, preoperative TTE exhibited
moderate or severe AS for all study patients, whereas, pre-CPB TEE demonstrated
mild AS in 5.4% (n = 92) of patients. CONCLUSIONS: The authors confirmed their
hypothesis that pre-CPB TEE generates different PGm and AVA values compared with
preoperative TTE. These differences often underestimate AS severity. Hemodynamic
standardizations or adjustments of pre-CPB TEE PGm and AVA values may be
necessary in anesthetized patients before assigning an AS grade using these
parameters.
PMID- 27495964
TI - Response to Letter to the Editor Concerning "The Optimal Angle of Head Rotation
for Internal Jugular Cannulation as Determined by Ultrasound Evaluation".
PMID- 27495963
TI - Noninvasive Positive-Pressure Ventilation in Treatment of Hypoxemia After
Extubation Following Type-A Aortic Dissection.
AB - OBJECTIVES: To assess the efficacy of noninvasive positive-pressure ventilation
(NPPV) in improving hypoxemia after extubation for Stanford type-A aortic
dissection and to compare NPPV using a mask or a helmet. DESIGN: Prospective,
interventional study. SETTING: Department of Cardiac Surgery of the Beijing
Anzhen Hospital, a tertiary university hospital. PARTICIPANTS: Patients
experiencing hypoxemia within 24 hours after extubation for Stanford type-A
aortic dissection. INTERVENTIONS: The patients were divided into the following 3
groups: high-flux inhalation of oxygen with a Venturi mask (control patients),
NPPV with a mask (mask group), and NPPV with a helmet (helmet group) (n =
25/group). MEASUREMENTS AND MAIN RESULTS: Data for blood gas analysis, vital
signs, heart function, and complications were collected before the treatment,
after 1 and 6 hours of treatment, and at the end of treatment. The oxygen partial
pressure/fraction of inspired oxygenation index or PaO2/FIO2 ratio and the oxygen
partial pressure were higher and carbon dioxide partial pressure was lower in the
mask and helmet groups compared with that of control patients. Compared with
control patients and the mask group, the helmet group showed a slower heart rate,
lower average arterial pressure, and improved left ventricular ejection fraction,
leading to a lower incidence of reintubation and a shorter hospital stay.
CONCLUSIONS: NPPV with a helmet may quickly improve oxygen partial pressure,
decrease carbon dioxide partial pressure, decrease the reintubation rate, and
effectively shorten the hospital stay after extubation for Stanford type-A aortic
dissection.
PMID- 27495966
TI - Effects of Levosimendan on Endothelial Function and Hemodynamics During Weaning
From Veno-Arterial Extracorporeal Life Support.
AB - OBJECTIVE: Weaning from veno-arterial extracorporeal life support is challenging.
The objective of this trial was to investigate the endothelial and hemodynamic
effects of levosimendan in cardiogenic shock patients supported with veno
arterial extracorporeal life support. DESIGN: This was a prospective
observational trial. SETTING: Cardiovascular intensive care unit of a large
tertiary care university hospital in Monza, Italy. PARTICIPANTS AND
INTERVENTIONS: Flow-mediated dilatation of the brachial artery and hemodynamic
parameters were assessed in 10 cardiogenic shock patients supported with veno
arterial extracorporeal life support, before and after the infusion of
levosimendan. MEASUREMENTS AND RESULTS: Flow-mediated dilatation increased both
as absolute value and as a percentage after levosimendan, from 0.10+/-0.12 to
0.61+/-0.21 mm (p<0.001) and from 3.2+/-4.2% to 17.8+/-10.4% (p<0.001),
respectively. Cardiac index increased from 1.93+/-0.83 to 2.64+/-0.97 L/min/m2 (p
= 0.008) while mixed venous oxygen saturation increased from 66.0% to 71.5% (p =
0.006) and arterial lactate levels decreased from 1.25 to 1.05 mmol/L (p = 0.004)
without significant variations in arterial oxygen saturation or hemoglobin
levels. This made it possible for clinicians to reduce extracorporeal membrane
oxygenation blood flow from 1.92+/-0.65 to 1.12+/-0.49 L/min/m2 (p<0.001).
CONCLUSION: In conclusion, in the authors' study population of adult cardiogenic
shock patients supported with veno-arterial extracorporeal life support, their
observations supported the use of levosimendan to improve endothelial function
and hemodynamics and facilitate weaning from the extracorporeal support.
PMID- 27495965
TI - Surgical Repair of Mitral Valve Disease in Children: Perioperative Changes in
Respiratory Function.
AB - OBJECTIVE: To assess the profile of changes in airway and respiratory tissue
mechanics within a follow-up study performed in children with mitral valve
disease, before and after surgical valve repair. DESIGN: Perioperative
measurements in a prospective, consecutive cross-sectional study. SETTING:
University hospital, tertiary care teaching hospital PARTICIPANTS: The study
comprised 24 children with congenital or post-rheumatic mitral valve
insufficiency. INTERVENTIONS: Input impedance of the respiratory system during
spontaneous breathing was measured before and 5 days and 3 weeks after mitral
valve surgery. In addition, airway and respiratory tissue mechanics and pulmonary
arterial pressure were assessed with the patient under general anesthesia
preoperatively and immediately postoperatively. Respiratory tissue elastance and
changes in airway measurements were estimated from forced oscillatory impedance
data by fitting an appropriate model. MEASUREMENT AND MAIN RESULTS: Relating
airway and respiratory tissue mechanics to previously established reference
values obtained in age-matched healthy control patients revealed abnormal
respiratory function (135+/-6.2% and 148+/-13% in respiratory elastance and
resistance, respectively; p<0.001). Improvement in the airway properties was
observed immediately after surgery (-15.2+/-3.4%; p<0.005) and lasted for the
study period (-19+/-4.1%; p<0.001). Respiratory tissue elastance, which
correlated preoperatively to the diastolic pulmonary arterial pressure, decreased
only 5 days postoperatively (-20.6+/-4.1%; p<0.005). However, there was no
evidence of a clear, immediate effect of surgery on the tissue mechanical
parameters measured intraoperatively despite a decrease in diastolic pulmonary
pressure. CONCLUSIONS: Mitral valve disease in children leads to abnormal airway
and respiratory tissue mechanics. Even though surgical repair of mitral
insufficiency alleviates abnormal airway function, residual lung tissue
stiffening may persist even weeks after the surgery, contributing to a sustained
impairment in lung function.
PMID- 27495969
TI - Voice Quality in Native and Foreign Languages Investigated by Inverse Filtering
and Perceptual Analyses.
AB - OBJECTIVES: Language shift from native (L1) to foreign language (L2) may affect
speaker's voice production and induce vocal fatigue. This study investigates the
effects of language shift on voice source and perceptual voice quality. STUDY
DESIGN: This is a comparative experimental study. SUBJECTS AND METHODS: Twenty
four subjects were recorded in L1 and L2. Twelve of the subjects were native
Finnish speakers and 12 were native English speakers, and the foreign languages
were English and Finnish. Two groups were created based on reports of
fatigability. Group 1 had the subjects who did not report more vocal fatigue in
L2 than in L1, and in group 2 those who reported more vocal fatigue in L2 than in
L1. Acoustic analyses by inverse filtering were conducted in L1 and L2. Also, the
subjects' voices were perceptually evaluated in both languages. RESULTS: Results
show that language shift from L1 to L2 increased perceived pressedness of voice.
Acoustic analyses correlated with the perceptual evaluations. Also, the subjects
who reported more vocal loading had poorer voice quality, more strenuous voice
production, more pressed phonation, and a higher pitch. CONCLUSIONS: Voice
production was less optimal in L2 than in L1. Speech training given in L2 could
be beneficial for people who need to use L2 extensively.
PMID- 27495967
TI - A nomogram for predicting pathological complete response in patients with human
epidermal growth factor receptor 2 negative breast cancer.
AB - BACKGROUND: The response to neoadjuvant chemotherapy has been proven to predict
long-term clinical benefits for patients. Our research is to construct a nomogram
to predict pathological complete response of human epidermal growth factor
receptor 2 negative breast cancer patients. METHODS: We enrolled 815 patients who
received neoadjuvant chemotherapy from 2003 to 2015 and divided them into a
training set and a validation set. Univariate logistic regression was performed
to screen for predictors and construct the nomogram; multivariate logistic
regression was performed to identify independent predictors. RESULTS: After
performing the univariate logistic regression analysis in the training set, tumor
size, hormone receptor status, regimens of neoadjuvant chemotherapy and cycles of
neoadjuvant chemotherapy were the final predictors for the construction of the
nomogram. The multivariate logistic regression analysis demonstrated that T4
status, hormone receptor status and receiving regimen of paclitaxel and
carboplatin were independent predictors of pathological complete response. The
area under the receiver operating characteristic curve of the training set and
the validation set was 0.779 and 0.701, respectively. CONCLUSIONS: We constructed
and validated a nomogram to predict pathological complete response in human
epidermal growth factor receptor 2 negative breast cancer patients. We also
identified tumor size, hormone receptor status and paclitaxel and carboplatin
regimen as independent predictors of pathological complete response.
PMID- 27495968
TI - Surgery or Rehabilitation: A Randomized Clinical Trial Comparing the Treatment of
Vocal Fold Polyps via Phonosurgery and Traditional Voice Therapy with "Voice
Therapy Expulsion" Training.
AB - OBJECTIVE: Phonomicrosurgery is generally considered to be the treatment of
choice for removing vocal fold polyps. However, specific techniques of voice
therapy may represent, in selected cases and under certain conditions, a
noninvasive therapeutic option for the treatment of such laryngeal lesions. The
aim of the present study is to longitudinally assess, in terms of clinical
outcomes and quality of life, two groups of patients with cordal polyps, treated
either with standard surgery plus standard voice therapy or with a specific
training of voice therapy alone, which we have called "Voice Therapy Expulsion."
STUDY DESIGN: This study is a randomized controlled trial. METHODS: A total of
150 patients with vocal fold polyps were randomly assigned to either standard
surgery or "voice therapy expulsion" protocol. The trial was carried out at the
Division of Phoniatrics and Audiology of the Second University of Naples and at
the Division of Communication Disorders of Local Health Unit (3 Naples South)
from January 2010 to December 2013. A thorough phoniatric evaluation, including
laryngostroboscopy, acoustic voice analysis, global grade of dysphonia,
instability, roughness, breathiness, asthenia, and strain scale, Voice Handicap
Index, and Voice-Related Quality of Life, was performed by using standardized
tools, at baseline, at the end of the treatment, and up to 1 year after
treatment. RESULTS: We found no significant differences between the two
experimental groups in terms of clinical outcomes and personal satisfaction.
However, "Voice Therapy Expulsion" was associated with higher scores for quality
of life at endpoint evaluation. CONCLUSIONS: Besides phonosurgery, this specific
"Voice Therapy Expulsion" technique should be considered as a valid, noninvasive,
and well-tolerated therapeutic option for the treatment of selected patients with
vocal fold polyps.
PMID- 27495970
TI - Esophageal Mucosal Impedance Pattern is Distinct in Patients With Extraesophageal
Reflux Symptoms and Pathologic Acid Reflux.
AB - OBJECTIVES/STUDY DESIGN: Current diagnostic tests for gastroesophageal reflux
disease (GERD) do not consistently measure chronicity of reflux. Mucosal
impedance (MI) is a minimally invasive measurement to assess esophageal
conductivity changes due to GERD. We aimed to investigate MI pattern in patients
with symptoms of extraesophageal reflux (EER) in a prospective longitudinal
cohort study. METHODS: Patients with potential symptoms of EER undergoing
esophagogastroduodenoscopy (EGD) with wireless pH monitoring were studied.
Participants included those with erosive esophagitis (E+), normal EGD/abnormal pH
(E-/pH+), and normal EGD/normal pH (E-/pH-). MI was measured from the site of
injury in patients with E+, as well as at 2, 5, and 10 cm above the
squamocolumnar junction (SCJ) in all participants. RESULTS: Forty-one patients
with symptoms of EER were studied. MI measurements at 2 cm above the SCJ were
significantly (P = 0.04) different among the three groups, with MI lowest for E+
and greatest for E-/pH- patients. Although not statistically significant, there
is a graded increase in median (interquartile range) MI axially along the
esophagus at 5 cm (P = 0.20) and at 10 cm (P = 0.27) above the SCJ, with those
with reflux (E+ and E-/pH+) having a lower MI than those without. CONCLUSIONS:
Patients with symptoms of EER and evidence of acid reflux have an MI lower than
those without at 2 cm above the SCJ, with a trend at 5 cm and 10 cm as well. MI
may be a tool to assess presence of GERD in patients presenting with EER
symptoms.
PMID- 27495972
TI - Divergent Successes: What the Abortion Rights Movement Can Learn from Marriage
Equality's Success.
PMID- 27495971
TI - Risk of self-reported symptoms or diagnosis of active tuberculosis in
relationship to low body mass index, diabetes and their co-occurrence.
AB - OBJECTIVE: Globally, tuberculosis prevalence has declined, but its risk factors
have varied across place and time - low body mass index (BMI) has persisted while
diabetes has increased. Using India's National Family Health Survey (NFHS), wave
3 and World Health Survey (WHS) data, we examined their relationships to support
projection of future trends and targeted control efforts. METHODS: Multivariate
logistic regressions at the individual level with and without diabetes/BMI
interactions assessed the relationship between tuberculosis, diabetes and low BMI
and the importance of risk factor co-occurrence. Population-level analyses
examined how tuberculosis incidence and prevalence varied with diabetes/low BMI
co-occurrence. RESULTS: In NFHS, diabetic individuals had higher predicted
tuberculosis risks (diabetic vs. non-diabetic: 2.50% vs. 0.63% at low BMI; 0.81%
vs. 0.20% at normal BMI; 0.37% vs. 0.09% at high BMI), which were not
significantly different when modelled independently or allowing for risk
modification with diabetes/low BMI co-occurrence. WHS findings were generally
consistent. Population-level analysis found that diabetes/low BMI co-occurrence
may be associated with elevated tuberculosis risk, although its predicted effect
on tuberculosis incidence/prevalence was generally <=0.2 percentage points and
not robustly statistically significant. CONCLUSIONS: Concerns about the
additional elevation of tuberculosis risk from diabetes/low BMI co-occurrence and
hence the need to coordinate tuberculosis control efforts around the nexus of co
occurring diabetes and low BMI may be premature. However, study findings robustly
support the importance of individually targeting low BMI and diabetes as part of
ongoing tuberculosis control efforts.
PMID- 27495973
TI - Bacterial Ice Nucleation in Monodisperse D2O and H2O-in-Oil Emulsions.
AB - Ice nucleation is of fundamental significance in many areas, including
atmospheric science, food technology, and cryobiology. In this study, we
investigated the ice-nucleation characteristics of picoliter-sized drops
consisting of different D2O and H2O mixtures with and without the ice-nucleating
bacteria Pseudomonas syringae. We also studied the effects of commonly used
cryoprotectants such as ethylene glycol, propylene glycol, and trehalose on the
nucleation characteristics of D2O and H2O mixtures. The results show that the
median freezing temperature of the suspension containing 1 mg/mL of a lyophilized
preparation of P. syringae is as high as -4.6 degrees C for 100% D2O, compared
to -8.9 degrees C for 100% H2O. As the D2O concentration increases every 25%
(v/v), the profile of the ice-nucleation kinetics of D2O + H2O mixtures
containing 1 mg/mL Snomax shifts by about 1 degrees C, suggesting an ideal
mixing behavior of D2O and H2O. Furthermore, all of the cryoprotectants
investigated in this study are found to depress the freezing phenomenon. Both the
homogeneous and heterogeneous freezing temperatures of these aqueous solutions
depend on the water activity and are independent of the nature of the solute.
These findings enrich our fundamental knowledge of D2O-related ice nucleation and
suggest that the combination of D2O and ice-nucleating agents could be a
potential self-ice-nucleating formulation. The implications of self-nucleation
include a higher, precisely controlled ice seeding temperature for slow freezing
that would significantly improve the viability of many ice-assisted
cryopreservation protocols.
PMID- 27495974
TI - Insight into the mechanism of chemical modification of antibacterial agents by
antibiotic resistance enzyme O-phosphotransferase-IIIA.
AB - In the present work, the mechanism of resistance to aminoglycoside antibiotics
was investigated. We examined the conformational changes of the O
phosphotransferase-IIIa enzyme, complexed with the antibiotics using MD
simulations. The inhibitory effects of a group of antibacterial peptides against
the enzyme were also examined, among which CP10A showed the highest affinity and
the results correlated with the measured IC50 values. The regioselectivity of the
phosphorylation reaction was shown to be in favor of the OH at the 5" position
versus the 3' of the antibiotic. The binding mode of CP10A was evaluated by means
of MD simulation that resulted in recognizing its Trp8 and Arg13 residues binding
near to where residues at the 3' and 5" positions of the antibiotic would bind;
thus, they are essential for the peptide inhibitory effect. The major open, semi
open, and closed conformations of the binding sites were identified throughout
the MD trajectory, which enable the enzyme to regulate the influx of molecules
into these sites. Based on the enzyme crystal structure, it was assumed that the
'antibiotic loop' of the enzyme is stable in its liganded mode; however, MD
results revealed that the loop is highly flexible in both liganded and ligand
free modes.
PMID- 27495976
TI - Diabetes-induced mechanophysiological changes in the esophagus.
AB - Esophageal disorders are common in diabetes mellitus (DM) patients. DM induces
mechanostructural remodeling in the esophagus of humans and animal models. The
remodeling is related to esophageal sensorimotor abnormalities and to symptoms
frequently encountered by DM patients. For example, gastroesophageal reflux
disease (GERD) is a common disorder associated with DM. This review addresses
diabetic remodeling of esophageal properties and function in light of the
Esophagiome, a scientifically based modeling effort to describe the physiological
dynamics of the normal, intact esophagus built upon interdisciplinary approaches
with applications for esophageal disease. Unraveling the structural,
biomechanical, and sensory remodeling of the esophagus in DM must be based on a
multidisciplinary approach that can bridge the knowledge from a variety of
scientific disciplines. The first focus of this review is DM-induced
morphodynamic and biomechanical remodeling in the esophagus. Second, we review
the sensorimotor dysfunction in DM and how it relates to esophageal remodeling.
Finally, we discuss the clinical consequences of DM-induced esophageal
remodeling, especially in relation to GERD. The ultimate aim is to increase the
understanding of DM-induced remodeling of esophageal structure and sensorimotor
function in order to assist clinicians to better understand the esophageal
disorders induced by DM and to develop better treatments for those patients.
PMID- 27495975
TI - Homozygous YME1L1 mutation causes mitochondriopathy with optic atrophy and
mitochondrial network fragmentation.
AB - Mitochondriopathies often present clinically as multisystemic disorders of
primarily high-energy consuming organs. Assembly, turnover, and surveillance of
mitochondrial proteins are essential for mitochondrial function and a key task of
AAA family members of metalloproteases. We identified a homozygous mutation in
the nuclear encoded mitochondrial escape 1-like 1 gene YME1L1, member of the AAA
protease family, as a cause of a novel mitochondriopathy in a consanguineous
pedigree of Saudi Arabian descent. The homozygous missense mutation, located in a
highly conserved region in the mitochondrial pre-sequence, inhibits cleavage of
YME1L1 by the mitochondrial processing peptidase, which culminates in the rapid
degradation of YME1L1 precursor protein. Impaired YME1L1 function causes a
proliferation defect and mitochondrial network fragmentation due to abnormal
processing of OPA1. Our results identify mutations in YME1L1 as a cause of a
mitochondriopathy with optic nerve atrophy highlighting the importance of YME1L1
for mitochondrial functionality in humans.
PMID- 27495977
TI - Target-site and non-target-site based resistance to the herbicide tribenuron
methyl in flixweed (Descurainia sophia L.).
AB - BACKGROUND: Flixweed (Descurainia sophia L.) is a troublesome and widespread
broadleaf weed in winter fields in China, and has evolved high level resistance
to acetolactate synthase (ALS)-inhibiting sulfonylurea herbicide tribenuron
methyl. RESULTS: We identified a resistant flixweed population (N11) exhibiting
116.3-fold resistance to tribenuron-methyl relative to the susceptible population
(SD8). Target-site ALS gene mutation Pro-197-Thr was identified in resistant
plants. Moreover, the resistance can be reversed to 28.7-fold by the cytochrome
P450 inhibitor malathion. The RNA-Sequencing was employed to identify candidate
genes involved in non-target-site metabolic resistance in this population. Total
26 differentially expressed contigs were identified and eight of them (four
P450s, one ABC transporter, three glycosyltransferase) verified by qRT-PCR.
Consistent over-expression of the two contigs homology to CYP96A13 and ABCC1
transporter, respectively, were further qRT-PCR validated using additional plants
from the resistant and susceptible populations. CONCLUSIONS: Tribenuron-methyl
resistance in flixweed is controlled by target-site ALS mutation and non-target
site based mechanisms. Two genes, CYP96A13 and ABCC1 transporter, could play an
important role in metabolic resistance to tribenuron-methyl in the resistant
flixweed population and justify further functional studies.
PMID- 27495978
TI - Use of a web-based educational intervention to improve knowledge of healthy diet
and lifestyle in women with Gestational Diabetes Mellitus compared to standard
clinic-based education.
AB - BACKGROUND: This study introduced a web-based educational intervention for
Australian women with gestational diabetes mellitus (GDM). The aim was to improve
knowledge on healthy diet and lifestyle in GDM. Evaluation of the intervention
explored women's knowledge and understanding of GDM, healthy diet, healthy food,
and healthy lifestyle, after using the web-based program compared to women
receiving standard clinic-based GDM education. METHODS: A total of 116 women,
aged 18-45 years old, newly diagnosed with GDM, participated (Intervention (n) =
56 and control (n) = 60). Women were randomly allocated to the intervention or
control groups and both groups attended a standard GDM education class. Group
1(Intervention) additionally used an online touch screen/computer program. All
women completed a questionnaire following the computer program and/or the
education class. All questions evaluating levels of knowledge had more than one
correct answer and scores were graded from 0 to 1, with each correct component
receiving a score, eg. 0.25 per each correct answer in a 4 answer question. Chi
square test was performed to compare the two groups regarding knowledge of GDM.
RESULTS: Findings indicated that the majority of women in the intervention group
reported correct answers for "types of carbohydrate foods" for pregnant women
with GDM, compared to the control group (62.5 % vs 58.3 %, respectively). Most
women in both groups had an excellent understanding of "fruits and vegetables"
(98.2 % vs 98.3 %), and the majority of women in the intervention group
understood that they should exercise daily for 30 min, compared to the control
group (92.9 % vs 91.7 %). Both groups had a good understanding across all
categories, however, the majority of women in the intervention group scored all
correct answers (score = 1) in term of foetal effects (17.9 % vs 13.3 %,
respectively), maternal predictors (5.4 % vs 5 %), care requirements (39.3 % vs
23.3 %), GDM perceptions (48.2 % vs 46.7 %) and GDM treatment (67.9 % vs 61.7 %),
compared to women in the control group. CONCLUSION: The study suggested that both
approaches, standard education and standard education plus web-based program,
resulted in excellent knowledge scores, but not statistically significant
difference between groups. Multiple and immediate access to the web-based
education program at home may prove useful as a source of reference for women
with GDM. Future study comparing results pre and post intervention is needed.
TRIAL REGISTRATION: ACTRN12615000697583 ; Date registered: 03/07/2015;
Retrospectively registered.
PMID- 27495979
TI - Contamination with ergot bodies (Claviceps purpurea sensu lato) of two horse
pastures in Northern Germany.
AB - Because the occurrence of Claviceps in European pastures may have been overlooked
to cause serious health problem for grazing animals, we documented the degree of
Claviceps contamination in two horse pastures and estimated whether the horses
could have ingested a critical quantity of alkaloids. We counted the Claviceps
sclerotia and determined alkaloid levels using high performance liquid
chromatography with fluorescence detection. Depending on the location, the number
of sclerotia varied from 0.09 to 0.19 per square meter (central area) and from
0.23 to 55.8 per square meter (border strips). Alkaloid levels in individual
sclerotia also varied in different genera of grasses, ranging from 0.98 +/- 0.17
MUg/kg in Agrostis sp. to 25.82 +/- 9.73 MUg/kg in Dactylis sp., equivalent to
0.98 MUg/kg and 7.26 mg/kg. Sclerotia from Dactylis contained high levels of
ergosine (0.209 % +/- 0.100 %) and ergocristine (0.374 % +/- 0.070 %). Depending
on the localization in pastures, alkaloid levels in forage (dry matter, DM)
ranged from 16.1 to 45.4 MUg/kg in central areas and from 23.9 to 722 MUg/kg in
border strips. The amount of alkaloids that a horse could have ingested depended
on its daily DM uptake, which was higher in the central areas (5.85 kg/day) than
in the border strips (2.73 or 0.78 kg/day). In the central areas, this amount of
alkaloids ranged from 94.2 to 265.9 MUg/day; and in the border strips, from 65.3
(in 2.73 kg DM/day) to as much as 563.8 MUg/day (in 0.78 kg DM/day). All these
amounts are higher than the European averages for alkaloids ingested by horses
via feedstuffs.
PMID- 27495982
TI - Correction for Hesse et al., Serological Responses to a Norovirus Nonstructural
Fusion Protein after Vaccination and Infection.
PMID- 27495980
TI - Strong predictive value of mannose-binding lectin levels for cardiovascular risk
of hemodialysis patients.
AB - BACKGROUND: Hemodialysis patients have higher rates of cardiovascular morbidity
and mortality compared to the general population. Mannose-binding lectin (MBL)
plays an important role in the development of cardiovascular disease. In
addition, hemodialysis alters MBL concentration and functional activity. The
present study determines the predictive value of MBL levels for future cardiac
events (C-event), cardiovascular events (CV-event) and all-cause mortality in HD
patients. METHODS: We conducted a prospective study of 107 patients on
maintenance hemodialysis. Plasma MBL, properdin, C3d and sC5b-9 was measured
before and after one dialysis session. The association with future C-events, CV
events, and all-cause mortality was evaluated using Cox regression models.
RESULTS: During median follow-up of 27 months, 36 participants developed 21 C
events and 36 CV-events, whereas 37 patients died. The incidence of C-events and
CV-events was significantly higher in patients with low MBL levels (<319 ng/mL,
lower quartile). In fully adjusted models, low MBL level was independently
associated with increased CV-events (hazard ratio 3.98; 95 % CI 1.88-8.24; P <
0.001) and C-events (hazard ratio 3.96; 95 % CI 1.49-10.54; P = 0.006). No
association was found between low MBL levels and all-cause mortality.
Furthermore, MBL substantially improved risk prediction for CV-events beyond
currently used clinical markers. CONCLUSIONS: Low MBL levels are associated with
a higher risk for future C-events and CV-events. Therefore, MBL levels may help
to identify hemodialysis patients who are at risk to develop cardiovascular
disease.
PMID- 27495984
TI - Remote ischemic preconditioning improves post resuscitation cerebral function via
overexpressing neuroglobin after cardiac arrest in rats.
AB - In this study, we investigated the effects of remote ischemic preconditioning on
post resuscitation cerebral function in a rat model of cardiac arrest and
resuscitation. The animals were randomized into six groups: 1) sham operation, 2)
lateral ventricle injection and sham operation, 3) cardiac arrest induced by
ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5)
remote ischemic preconditioning initiated 90min before induction of ventricular
fibrillation, and 6) lateral ventricle injection and remote ischemic
preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is
neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham
operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic
preconditioning was induced by four cycles of 5min of limb ischemia, followed by
5min of reperfusion. Ventricular fibrillation was induced by current and lasted
for 6min. Defibrillation was attempted after 6min of cardiopulmonary
resuscitation. The animals were then monitored for 2h and observed for an
additionally maximum 70h. Post resuscitation cerebral function was evaluated by
neurologic deficit score at 72h after return of spontaneous circulation. Results
showed that remote ischemic preconditioning increased neurologic deficit scores.
To investigate the neuroprotective effects of remote ischemic preconditioning, we
observed neuronal injury at 48 and 72h after return of spontaneous circulation
and found that remote ischemic preconditioning significantly decreased the
occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of
neuroprotection induced by remote ischemic preconditioning, we found expression
of neuroglobin at 24h after return of spontaneous circulation was enhanced.
Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before
induction of remote ischemic preconditioning showed that the level of neuroglobin
was decreased then partly abrogated neuroprotection of remote ischemic
preconditioning. These date suggested that neuroglobin involved in
neuroprotective effect of remote ischemic preconditioning. In conclusion, remote
ischemic preconditioning attenuated post resuscitation cerebral dysfunction and
the neuroprotection was mediated partly by high level of neuroglobin in a rat
model of cardiac arrest and resuscitation.
PMID- 27495985
TI - Can an auditory multi-feature optimal paradigm be used for the study of processes
associated with attention capture in passive listeners?
AB - OBJECTIVE: A rarely occurring and highly relevant auditory stimulus occurring
outside of the current focus of attention can cause a switching of attention.
Such attention capture is often studied in oddball paradigms consisting of a
frequently occurring "standard" stimulus which is changed at odd times to form a
"deviant". The deviant may result in the capturing of attention. An auditory ERP,
the P3a, is often associated with this process. To collect a sufficient amount of
data is however very time-consuming. A more multi-feature "optimal" paradigm has
been proposed but it is not known if it is appropriate for the study of attention
capture. METHODS: An optimal paradigm was run in which 6 different rare deviants
(p=.08) were separated by a standard stimulus (p=.50) and compared to results
when 4 oddball paradigms were also run. RESULTS: A large P3a was elicited by some
of the deviants in the optimal paradigm but not by others. However, very similar
results were observed when separate oddball paradigms were run. CONCLUSIONS &
SIGNIFICANCE: The present study indicates that the optimal paradigm provides a
very time-saving method to study attention capture and the P3a.
PMID- 27495986
TI - Early rehabilitation aggravates brain damage after stroke via enhanced activation
of nicotinamide adenine dinucleotide phosphate oxidase (NOX).
AB - INTRODUCTION: Although physical exercise has emerged as a potential therapeutic
modality for functional deficits following ischemic stroke, the extent of this
effect appears to be contingent upon the time of exercise initiation. In the
present study, we assessed how exercise timing affected brain damage through
hyperglycolysis-associated NADPH oxidase (NOX) activation. METHODS: Using an
intraluminal filament, adult male Sprague-Dawley rats were subjected to middle
cerebral artery occlusion (MCAO) for 2h and assigned to one non-exercise and
three exercise groups. Exercise on Rota-rod was initiated for 30min at 6h
(considered very early), at 24h (early), and at day 3 (relatively late) after
reperfusion. Lactate production was measured 30min after exercise completion, and
NOX activity and protein expression of NOX subunits (p47(phox), gp91(phox),
p22(phox) and p67(phox)) and glucose transporter 1 and 3 (Glut-1 and -3) were
measured at 3 and 24h after exercise. Apoptotic cell death was determined at 24h
after exercise. RESULTS: Lactate production and Glut-1 and Glut-3 expression were
increased after very early exercise (6h), but not after late exercise (3 days),
suggesting hyperglycolysis. NOX activity was increased with the initiation of
exercise at 6h (P<0.05), but not 24h or 3 days, following stroke. Early (6 and
24h), but not late (3 days), post-stroke exercise was associated with increased
(P<0.05) expression of the NOX protein subunit p47(phox), gp91(phox)and
p67(phox). This may have led to the enhanced apoptosis observed after early
exercise in ischemic rats. CONCLUSION: Hyperglycolysis and NOX activation was
associated with an elevation in apoptotic cell death after very early exercise,
and the detrimental effect of exercise on stroke recovery began to decrease when
exercise was initiated 24h after reperfusion.
PMID- 27495987
TI - Visceral leishmaniasis in a lung transplant recipient: usefulness of highly
sensitive real-time polymerase chain reaction for preemptive diagnosis.
AB - We report the case of a lung transplant recipient in whom the diagnosis of
visceral leishmaniasis (VL) was made by detection of parasites in a peripheral
blood smear when the parasite load already reached 8.9 * 103 parasites/mL. We
demonstrated that the VL diagnosis could have been done months before the
development of symptoms by the use of Leishmania-specific real-time polymerase
chain reaction (PCR), suggesting the role of preemptive PCR-based diagnosis in
transplant recipients at risk for VL.
PMID- 27495988
TI - Next-generation sequencing survey of biliary tract cancer reveals the association
between tumor somatic variants and chemotherapy resistance.
AB - BACKGROUND: Biliary tract cancers (BTCs) are uncommon and are associated with a
dismal prognosis. Combinations of gemcitabine and platinum chemotherapy
(gemcitabine and platinum-based therapy [GP]) form the standard approach for
treating advanced BTC. To characterize the spectrum of mutations and to identify
potential biomarkers for a GP response in BTC, this study evaluated the genomic
landscape and assessed whether mutations affecting DNA repair were associated
with GP resistance. METHODS: Pretreatment, formalin-fixed, paraffin-embedded
samples from 183 BTC patients treated with GP were analyzed. Cox regression
models were used to determine the association between mutations, progression-free
survival (PFS), and overall survival (OS). RESULTS: When genes with an incidence
> 10% were considered, no individual gene was independently predictive of a GP
response. In patients with unresectable BTC who received GP as their first-line
therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor
protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with
PFS (P = .0004) and OS (P <= .0001). Patients with mutations in CDKN2A and TP53
were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a
median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single
mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited
mutations in all 3 genes had a median PFS of 20.37 months, and OS was not
reached. CONCLUSIONS: In the largest exploratory analysis of this kind for BTC, 3
prevalent, mutually exclusive mutations represent distinct patient cohorts. These
mutations are prognostic and may represent a predictive biomarker for a GP
response. Prospective studies to validate these findings are needed, and they
should include the incorporation of therapies that exploit the genomic
instability observed with these mutations in BTC. Cancer 2016;122:3657-66. (c)
2016 American Cancer Society.
PMID- 27495990
TI - Body size limits dim-light foraging activity in stingless bees (Apidae:
Meliponini).
AB - Stingless bees constitute a species-rich tribe of tropical and subtropical
eusocial Apidae that act as important pollinators for flowering plants. Many
foraging tasks rely on vision, e.g. spatial orientation and detection of food
sources and nest entrances. Meliponini workers are usually small, which sets
limits on eye morphology and thus quality of vision. Limitations are expected
both on acuity, and thus on the ability to detect objects from a distance, as
well as on sensitivity, and thus on the foraging time window at dusk and dawn. In
this study, we determined light intensity thresholds for flight under dim light
conditions in eight stingless bee species in relation to body size in a
Neotropical lowland rainforest. Species varied in body size (0.8-1.7 mm thorax
width), and we found a strong negative correlation with light intensity
thresholds (0.1-79 lx). Further, we measured eye size, ocelli diameter, ommatidia
number, and facet diameter. All parameters significantly correlated with body
size. A disproportionately low light intensity threshold in the minute Trigonisca
pipioli, together with a large eye parameter P eye suggests specific adaptations
to circumvent the optical constraints imposed by the small body size. We discuss
the implications of body size in bees on foraging behavior.
PMID- 27495989
TI - Knockout maternal adiponectin increases fetal growth in mice: potential role for
trophoblast IGFBP-1.
AB - AIMS/HYPOTHESIS: The main objective of this study was to investigate whether
maternal adiponectin regulates fetal growth through the endocrine system in the
fetal compartment. METHODS: Adiponectin knockout (Adipoq (-/-) ) mice and in vivo
adenovirus-mediated reconstitution were used to study the regulatory effect of
maternal adiponectin on fetal growth. Primary human trophoblast cells were
treated with adiponectin and a specific peroxisome proliferator-activated
receptor alpha (PPARalpha) agonist or antagonist to study the underlying
mechanism through which adiponectin regulates fetal growth. RESULTS: The body
weight of fetuses from Adipoq (-/-) dams was significantly greater than that of
wild-type dams at both embryonic day (E)14.5 and E18.5. Adenoviral vector
mediated maternal adiponectin reconstitution attenuated the increased fetal body
weight induced by maternal adiponectin deficiency. Significantly increased blood
glucose, triacylglycerol and NEFA levels were observed in Adipoq (-/-) dams,
suggesting that nutrient supply contributes to maternal adiponectin-regulated
fetal growth. Although fetal blood IGF-1 concentrations were comparable in
fetuses from Adipoq (-/-) and wild-type dams, remarkably low levels of IGF
binding protein 1 (IGFBP-1) were observed in the serum of fetuses from Adipoq (-/
) dams. IGFBP-1 was identified in the trophoblast cells of human and mouse
placentas. Maternal fasting robustly increased IGFBP-1 levels in mouse placentas,
while reducing fetal weight. Significantly low IGFBP-1 levels were found in
placentas of Adipoq (-/-) dams. Adiponectin treatment increased IGFBP-1 levels in
primary cultured human trophoblast cells, while the PPARalpha antagonist, MK886,
abolished this stimulatory effect. CONCLUSIONS/INTERPRETATION: These results
indicate that, in addition to nutrient supply, maternal adiponectin inhibits
fetal growth by increasing IGFBP-1 expression in trophoblast cells.
PMID- 27495991
TI - Triple bypass for advanced pancreatic head cancer associated with biliary
stricture, duodenal stenosis, and recurrent obstructive pancreatitis.
AB - Bypass surgery for cancer of the pancreatic head is usually done to palliate the
obstructive symptoms in the biliary and/or digestive system. However, it is
uncommon for patients to require pancreatic duct drainage for recurrent
obstructive pancreatitis. In this article, we report a surgical technique of
triple bypass consisting of Roux-en-Y hepaticojejunostomy, gastrojejunostomy, and
pancreaticojejunostomy for advanced pancreatic cancer. A 76-year-old male patient
with locally advanced and metastatic pancreatic head cancer was referred to our
department for biliary stricture, duodenal stenosis, and recurrent obstructive
pancreatitis associated with persistent pancreatic pseudocyst. In an attempt to
resolve all these problems simultaneously, a triple bypass was performed. The
patient survived and continued to receive chemotherapy for almost 1 year after
surgery without any serious complications. Thus, triple bypass is a useful
surgical technique that could relief symptoms and offer better quality of life to
patients with advanced pancreatic cancer presenting with biliary stricture,
duodenal stenosis, and severe obstructive pancreatitis difficult to treat by
medication or endoscopic procedures.
PMID- 27495992
TI - Wandering liver and intestinal malrotation: first report.
AB - A wandering liver is a rare development in both the adult and pediatric
population where the liver is freely displaced along a transverse axis. We
describe the first known occurrence in published literature of a wandering liver
in an adult individual who also had an intestinal malrotation complicated by a
midgut volvulus. The abnormal ability for a liver to wander presents a highly
unusual anatomy that can be disorienting. Laparoscopic surgery is a viable option
in reducing a midgut volvulus and addressing an intestinal malrotation in the
presence of a wandering liver. This unusual presentation educates clinicians to
avoid potential misdiagnosis given the abnormal location of the duodenum,
appendix, liver, and gallbladder.
PMID- 27495993
TI - Efficacy of recombinant thrombomodulin for DIC after deceased donor liver
transplantation: a case report.
AB - BACKGROUND: Disseminated intravascular coagulation (DIC) after liver
transplantation (LT) is a difficult complication. We report a case of
disseminated intravascular coagulation after deceased donor liver transplantation
(DDLT) treated with recombinant thrombomodulin (rTM). CASE PRESENTATION: A 30
year-old woman underwent right tri-segment split graft DDLT for acute liver
failure. She developed disseminated intravascular coagulation on post-operative
day 5 with fever. Computed tomography revealed necrosis of hepatic segment IV,
and her acute-phase disseminated intravascular coagulation score was seven
points. She was given rTM, and the inflammation, liver function, and coagulation
disorders immediately improved. However, pleural effusion drainage from the chest
tube became bloody on post-operative day 11, and rTM was discontinued. She
progressed well and was discharged from the hospital on post-operative day 28.
rTM is an effective treatment for disseminated intravascular coagulation;
however, rTM for cases with coagulation disorders, which can occur after liver
transplantation, has both risks and benefits. CONCLUSIONS: We report a case of
DIC after LT, in which rTM was potentially effective. Further studies are needed
to determine the appropriate dosages, duration, and additional considerations for
rTM therapy in liver transplantation patients.
PMID- 27495994
TI - Diastology: What Does the New Updated Guideline Do for You?
PMID- 27495995
TI - Renovascular Duplex Ultrasound in Children: A Lost Cause?
PMID- 27495997
TI - Feasibility and Prognostic Effect of Sentinel Lymph Node Biopsy After Neoadjuvant
Chemotherapy in Cytology-Proven, Node-Positive Breast Cancer.
AB - BACKGROUND: We evaluated the feasibility and prognostic effect in axillary
recurrence or survival of sentinel lymph node biopsy (SLNB) in patients with
cytology-proven, node-positive breast cancer after neoadjuvant chemotherapy
(NAC). METHODS: This is a retrospective study of 329 patients who were diagnosed
with invasive breast cancer and axillary lymph nodes (ALN) metastasis and treated
with NAC followed by curative surgery at Samsung Medical Center between January
2007 and December 2013. We analyzed and compared outcomes including prognoses and
survival rates among all groups. RESULTS: The median age at the time of surgery
was 44.4 years. The median follow-up time was 37 months (range, 1-91 months). The
sentinel lymph node (SLN) identification rate was 96.7% (117 of 121 patients).
The median number of retrieved SLNs was 4.0 (range, 1-7), and 57 patients had
negative SLNs on frozen-section analysis. The false negative rate of SLNB after
NAC was 7.8% (5 of 64 patients). In survival analysis, there was no difference in
the overall survival (P = .2) and the regional recurrence-free survival (P =
.297) among Groups 1, 2, and 4. CONCLUSION: SLNB may be feasible after NAC for
node-positive breast cancer and may help reduce surgical morbidity by avoiding
the need for standard axillary lymph node dissection in some patients. We suggest
that future studies with a large number of patients and a longer follow-up period
are necessary to support the use of SLN surgery as an alternative to axillary
lymph node dissection in this patient population.
PMID- 27495996
TI - Comparing Coordinated Versus Sequential Salpingo-Oophorectomy for BRCA1 and BRCA2
Mutation Carriers With Breast Cancer.
AB - BACKGROUND: Women with breast cancer who carry BRCA1 or BRCA2 mutations must also
consider risk-reducing salpingo-oophorectomy (RRSO) and how to coordinate this
procedure with their breast surgery. We report the factors associated with
coordinated versus sequential surgery and compare the outcomes of each. PATIENTS
AND METHODS: Patients in our cancer risk database who had breast cancer and a
known deleterious BRCA1/2 mutation before undergoing breast surgery were
included. Women who chose concurrent RRSO at the time of breast surgery were
compared to those who did not. RESULTS: Sixty-two patients knew their mutation
carrier status before undergoing breast cancer surgery. Forty-three patients
(69%) opted for coordinated surgeries, and 19 (31%) underwent sequential
surgeries at a median follow-up of 4.4 years. Women who underwent coordinated
surgery were significantly older than those who chose sequential surgery (median
age of 45 vs. 39 years; P = .025). There were no differences in comorbidities
between groups. Patients who received neoadjuvant chemotherapy were more likely
to undergo coordinated surgery (65% vs. 37%; P = .038). Sequential surgery
patients had longer hospital stays (4.79 vs. 3.44 days, P = .01) and longer
operating times (8.25 vs. 6.38 hours, P = .006) than patients who elected
combined surgery. Postoperative complications were minor and were no more likely
in either group (odds ratio, 4.76; 95% confidence interval, 0.56-40.6).
CONCLUSION: Coordinating RRSO with breast surgery is associated with receipt of
neoadjuvant chemotherapy, longer operating times, and hospital stays without an
observed increase in complications. In the absence of risk, surgical options can
be personalized.
PMID- 27495999
TI - Smoking rates vary widely in US racial and ethnic groups.
PMID- 27495998
TI - Design and evaluation of a portable intra-operative unified-planning-and-guidance
framework applied to distal radius fracture surgery.
AB - PURPOSE: During a standard fracture reduction and fixation procedure of the
distal radius, only fluoroscopic images are available for planning of the screw
placement and monitoring of the drill bit trajectory. Our prototype intra
operative framework integrates planning and drill guidance for a simplified and
improved planning transfer. METHODS: Guidance information is extracted using a
video camera mounted onto a surgical drill. Real-time feedback of the drill bit
position is provided using an augmented view of the planning X-rays. We evaluate
the accuracy of the placed screws on plastic bones and on healthy and fractured
forearm specimens. We also investigate the difference in accuracy between guided
screw placement versus freehand. Moreover, the accuracy of the real-time position
feedback of the drill bit is evaluated. RESULTS: A total of 166 screws were
placed. On 37 plastic bones, our obtained accuracy was [Formula: see text] mm,
[Formula: see text] and [Formula: see text] in tip position and orientation
(azimuth and elevation), respectively. On the three healthy forearm specimens,
our obtained accuracy was [Formula: see text] mm, [Formula: see text] and
[Formula: see text]. On the two fractured specimens, we attained: [Formula: see
text] mm, [Formula: see text] and [Formula: see text]. When screw plans were
applied freehand (without our guidance system), the achieved accuracy was
[Formula: see text] mm, [Formula: see text], while when they were transferred
under guidance, we obtained [Formula: see text] mm, [Formula: see text].
CONCLUSIONS: Our results show that our framework is expected to increase the
accuracy in screw positioning and to improve robustness w.r.t. freehand
placement.
PMID- 27496000
TI - Editorial overview: New technologies: GPCR drug design and function-exploiting
the current (of) structures.
PMID- 27496001
TI - Management of Simple Clavicle Fractures by Primary Care Physicians.
AB - The clavicle is the most commonly fractured bone. Children with simple fractures
are often referred to orthopedic surgeons by primary care physician to ensure
adequate care. The objective of this study was to show that simple clavicle
fractures have excellent outcomes and are within the scope of primary care
physician's practice. We performed a retrospective chart review of 16 adolescents
with simple clavicle fractures treated with a sling. Primary outcomes were bony
union, pain, and function. The patients with simple clavicle fractures had
excellent outcomes with no complications or complaints of pain or restriction of
their activities of daily living. The outcomes are similar whether treated by an
orthopedic surgeon or a primary care physician. The cost to society and the
patient is less when the primary care physician manages the fracture. Therefore,
primary care physicians should manage simple clavicle fractures.
PMID- 27496003
TI - Exposure to zidovudine adversely affects mitochondrial turnover in primary T
cells.
AB - Zidovudine (ZDV) is a widely used component of antiretroviral therapy (ART) in
resource-limited settings, despite its known adverse effects, which include
mitochondrial toxicity in muscle, liver and adipose tissue. It has also been
associated with impaired immunological recovery. We hypothesised that ZDV might
impair mitochondrial health and survival of primary T cells. We performed a cross
sectional analysis of mitochondrial function, mitophagy and susceptibility to
apoptosis in healthy donor primary T cells after exposure to ZDV in vitro,
together with T cells from patients who were virologically suppressed on ZDV
containing ART regimens for >=1 year and age-matched subjects receiving non-ZDV
ART regimens. The proportion of T cells expressing mitochondrial reactive oxygen
species (mtROS) was significantly higher after in vitro (CD4(+) T cells and
CD8(+) T cells) and in vivo (CD4(+) T cells) exposure to ZDV than other
antiretroviral agents. We did not detect any effect of ZDV on mitophagy, as
indicated by change in autophagic flux. However, spontaneous apoptosis, indicated
by upregulation of caspase-3 was greater in ZDV-exposed T cells. In conclusion,
ZDV exposure was associated with impaired mitochondrial turnover and increased
susceptibility to apoptosis in T cells. These mechanisms could contribute to sub
optimal immune reconstitution.
PMID- 27496002
TI - Optogenetic Approaches for Controlling Seizure Activity.
AB - Optogenetics, a technique that utilizes light-sensitive ion channels or pumps to
activate or inhibit neurons, has allowed scientists unprecedented precision and
control for manipulating neuronal activity. With the clinical need to develop
more precise and effective therapies for patients with drug-resistant epilepsy,
these tools have recently been explored as a novel treatment for halting seizure
activity in various animal models. In this review, we provide a detailed and
current summary of these optogenetic approaches and provide a perspective on
their future clinical application as a potential neuromodulatory therapy.
PMID- 27496006
TI - Endoscopic-modified medial maxillectomy and its limitation for a solitary fibrous
tumor of the lacrimal sac and nasolacrimal duct.
AB - Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the
pleura. Recently, SFTs have been reported in the head and neck region located in
subsites such as the orbit. SFTs of the lacrimal sac are extremely rare, with
only six cases reported in the English literature. We describe a SFT arising from
the right lacrimal sac and extending along the nasolacrimal duct into the nasal
cavity. Although, the tumor could not be removed by endoscopic-modified medial
maxillectomy (EMMM) alone, combined approach with EMMM and a small external
incision achieved the complete removal of the tumor. The patient has remained
disease-free 24 months after surgery.
PMID- 27496004
TI - Exosomes contribute to the transmission of anti-HIV activity from TLR3-activated
brain microvascular endothelial cells to macrophages.
AB - Human brain microvascular endothelial cells (HBMECs), the major cell type in the
blood-brain barrier (BBB), play a key role in maintaining brain homeostasis.
However, their role in the BBB innate immunity against HIV invasion of the
central nervous system (CNS) remains to be determined. Our early work showed that
TLR3 signaling of HBMECs could produce the antiviral factors that inhibit HIV
replication in macrophages. The present study examined whether exosomes from TLR3
activated HBMECs mediate the intercellular transfer of antiviral factors to
macrophages. Primary human macrophages could take up exosomes from TLR3-activated
HBMECs. HBMECs-derived exosomes contained multiple antiviral factors, including
several key IFN-stimulated genes (ISGs; ISG15, ISG56, and Mx2) at mRNA and
protein levels. The depletion of exosomes from TLR3-activated HBMECs culture
supernatant diminished HBMECs-mediated anti-HIV activity in macrophages. In
conclusion, we demonstrate that exosomes shed by HBMECs are able to transport the
antiviral molecules to macrophages. This finding suggests the possibility that
HIV nonpermissive BBB cells (HBMECs) can help to restore the antiviral state in
HIV-infected macrophages, which may be a defense mechanism against HIV
neuroinvasion.
PMID- 27496007
TI - A case of vertebral artery aneurysm presenting with dysphagia.
AB - Here, we report a case of vertebral artery aneurysm causing dysphagia in a 56
year-old man who had no remarkable past history. Two months before the first
visit, he developed posterior neck pain followed by difficulty swallowing 1 month
later. He was referred to our clinic because of gradually worsening dysphagia.
Physical examination showed paralysis of cranial nerves IX, X, and XII;
therefore, he was hospitalized. Because enhanced CT and MRI showed a partially
thrombosed right vertebral artery aneurysm, he was transferred to the care of the
Department of Neurosurgery. Parent artery occlusion of the right vertebral artery
aneurysm was performed and it improved his symptoms. After regaining his ability
to take in liquid food, he was transferred to another hospital for further
rehabilitation. In this case, we attributed the dysphagia to aneurysmal
compression of the roots of cranial nerves IX, X, and XII. A partially thrombosed
cerebral artery aneurysm may often rupture and cause worsening of neurologic
symptoms. The prognosis is generally poor because the rupture rate is extremely
high especially with large or giant aneurysms. However, this case had a good
clinical course owing to treatment by parent artery occlusion.
PMID- 27496008
TI - Sentinel node biopsy for oral cancer: A prospective multicenter Phase II trial.
AB - OBJECTIVE: A recent study identified a survival benefit with prophylactic neck
dissection (ND) at the time of primary surgery as compared with watchful waiting
followed by therapeutic neck dissection for nodal relapse, in patients with cN0
oral squamous cell carcinoma (OSCC). Alternative management of cN0 neck cancer is
recommended to minimize the adverse effects of ND, indicating the need for
sentinel node biopsy (SNB) and limited neck dissection. We conducted a
multicenter Phase II study to examine the feasibility of SNB for clinically N0
OSCC. METHODS: Previously untreated N0 OSCC patients (n=57) with clinical late-T2
or T3 tumors were enrolled across 10 institutions. SNB navigated with multislice
frozen section analysis of sentinel nodes (SNs) and SNB supported sentinel node
lymphatic basin dissection (SN basin dissection) were performed in a one-stage
procedure. The endpoint was to investigate the rate of false-negative metastases
after SN basin dissection and SNB alone. RESULTS: Most tumors were late-T2
lesions (n=50; 87.7%). SNs were identified in all patients. A total of 196 SNs
were detected. Among these SNs, 35 (17.8%) were positive for metastasis (9 in
level I, 12 in level II, 12 in level III, 1 in level V and 2 in the contralateral
region of the neck). The false-negative rate of SNB supported by SN basin
dissection and SNB alone was 4.5% and 9.1%, respectively. The concordance of the
SN status in intraoperative frozen sections with the permanent histopathology was
97.4% (191/196). The sensitivity and specificity of intraoperative pathological
evaluation were 85.7% (30/35) and 100% (30/30), respectively. The 3-year overall
survival (OS) and disease-free survival was 89.5% and 82.5%, respectively. The OS
of SN-negative patients was significantly longer than that of SN-positive
patients (P=0.047). CONCLUSION: The current study verified that SN basin
dissection was a useful back-up procedure for SNB performed as a one-stage
procedure, showing a low false-negative rate. SNB alone is an appropriate staging
method for patients with clinical N0 staging, and a reliable procedure to
determine the appropriate levels for neck dissection.
PMID- 27496009
TI - Primary combined small cell carcinoma and squamous cell carcinoma of the
oropharynx with special reference to EGFR status of small cell carcinoma
component: Case report and review of the literature.
AB - Combined small cell carcinoma (SCC) and squamous cell carcinoma (SqCC) of the
oropharynx is extremely rare and shows an aggressive clinical course. There are
only 5 reported cases of combined SCC and SqCC in the English language
literature. Here, we report a 59-year-old male presenting with a right tonsillar
mass. The mass was biopsied, and the histological findings showed a proliferation
of small-sized tumor cells with scant cytoplasm. Immunohistochemically, the tumor
cells were positive for neuroendocrine markers (synaptophysin, chromogranin A,
and CD56). Our first diagnosis was tonsillar small cell carcinoma. We treated the
patient with concurrent chemoradiotherapy together with cisplatin followed by
surgery. The resected tonsillar specimen showed a residual tumor composed of SCC
and SqCC, and lymph nodes showed metastatic tumor cells of the SCC component.
Immunohistochemically, the SCC component was positive for all neuroendocrine
markers and p16; on the other hand, the SqCC component was positive for p40, p63,
p16, and EGFR. Fluorescence in situ hybridization revealed that neither component
showed any EGFR gene copy number gain. The patient was treated with adjuvant
chemotherapy consisting of irinotecan and cisplatin. Liver and bone metastases
developed, resulting in the death of the patient. We discuss the present case and
review similar cases. Most cases of combined SCC and SqCC occur regardless of p16
status, and a therapeutic strategy has yet to be determined. Further examination
of this kind of combined tumor is necessary.
PMID- 27496010
TI - Stress hormonal changes in the brain and plasma after acute noise exposure in
mice.
AB - OBJECTIVE: To investigate the effects of acute noise stress on two amine stress
hormones, norepinephrine (NE) and 5-hydroxyindoleacetic acid (5-HIAA) in the
brain and plasma of mice after noise exposure. METHODS: Mice were grouped into
the control and noise groups. Mice in the noise group were exposed to white noise
of 110dB sound pressure level for 60min. Auditory brainstem response thresholds,
distortion product otoacoustic emissions, the organ of Corti grading scores,
western blots of NE/5-HIAA in the whole brain and hippocampus, and the plasma
levels of NE/5-HIAA were compared between the two groups. RESULTS: Significant
hearing loss and cochlear damage were demonstrated in the noise group. NE and 5
HIAA in the hippocampus were elevated in the noise group (p=0.019/0.022 for NE/5
HIAA vs. the control). Plasma levels of NE and 5-HIAA were not statistically
different between the groups (p=0.052/0.671 for NE/5-HIAA). CONCLUSION: Hearing
loss with outer hair cell dysfunction and morphological changes of the organ of
Corti after noise exposure in C57BL/6 mice proved the reliability of our animal
model as an acute noise stress model. NE and 5-HIAA are suggested to be the
potential biomarkers for acute noise stress in the hippocampus.
PMID- 27496011
TI - Palpebral sporotrichosis in a 6-year-old child.
PMID- 27496012
TI - A GIS Approach to Identifying Socially and Medically Vulnerable Older Adult
Populations in South Florida.
AB - Purpose of the Study: We define, map, and analyze geodemographic patterns of
socially and medically vulnerable older adults within the tri-county region of
South Florida. Design and Methods: We apply principal components analysis (PCA)
to a set of previously identified indicators of social and medical vulnerability
at the census tract level. We create and map age-stratified vulnerability scores
using a geographic information system (GIS), and use spatial analysis techniques
to identify patterns and interactions between social and medical vulnerability.
Results: Key factors contributing to social vulnerability in areas with higher
numbers of older adults include age, large household size, and Hispanic
ethnicity. Medical vulnerability in these same areas is driven by disease burden,
access to emergency cardiac services, availability of nursing home and hospice
beds, access to home health care, and available mental health services. Age
dependent areas of social vulnerability emerge in Broward County, whereas age
dependent areas of medical vulnerability emerge in Palm Beach County. Older-adult
social and medical vulnerability interact differently throughout the study area.
Implications: Spatial analysis of older adult social and medical vulnerability
using PCA and GIS can help identify age-dependent pockets of vulnerability that
are not easily identifiable in a populationwide analysis; improve our
understanding of the dynamic spatial organization of health care, health care
needs, access to care, and outcomes; and ultimately serve as a tool for health
care planning.
PMID- 27496013
TI - Culture and Language Discordance in the Workplace: Evidence From the National
Home Health Aide Survey.
AB - Purpose of the study: Home health aides (HHAs) provide valuable resources to
address existing and predicted needs for taking care of the aging population.
Both the older adult and healthcare provider populations in the United States are
becoming increasingly diverse. The study examined the effect of culture and
language discordance between HHAs and their patients or coworkers on worker
outcomes. Design and methods: Data from this study were from the 2007 National
Home Health Aide Survey. T Tests and ordinary least squares regression were used
to analyze the relationships between cultural discordance and worker outcomes.
Results: Cultural discordance with patients was associated with lower levels of
job satisfaction among HHAs. Cultural discordance with coworkers was associated
with lower levels of job satisfaction and, increased intent to leave one's job.
Implications: The current study suggests that cultural discordance does affect
worker outcomes. However, home healthcare workers appear to differentiate between
cultural discordance with patients and with coworkers. This article concludes
with strategies for all involved in the care of older adults to improve the
experience of HHAs and to ensure patients receive the best possible care.
PMID- 27496014
TI - Fitness-to-drive Disagreements in Individuals With Dementia.
AB - Purpose of the Study: We sought to investigate the agreement between medical and
practical fitness-to-drive recommendations in active drivers with dementia.
Design and Methods: In this retrospective study, 68 patients underwent medical,
visual, and road tests at an official center of the Belgian Road Safety
Institute. Physicians provided medical fitness-to-drive recommendations using 1
of 3 categories (favorable, reserved, or unfavorable). On-road assessors used the
same 3 categories to make practical fitness-to-drive recommendations. Agreement
between the medical and practical fitness-to-drive recommendations was calculated
using the percentage of agreement (p0) and weighted kappa (kw). Results: Low
agreement was found between physicians and on-road assessors regarding their
fitness-to-drive recommendations (p0 = 43%, kw = 0.11, p = .20). Compared with
the on-road assessors, the physicians overestimated the fitness to drive of 24
(35%) patients and underestimated the fitness to drive of 15 (22%) patients.
Patients who incurred more traffic violations were more likely to be
overestimated than underestimated by the physician (p = .03). Implications: This
study showed disagreements between the fitness-to-drive recommendations made by
the physicians and the on-road assessors in more than half of drivers with
dementia. Efforts need to be made to improve the communication between physicians
and on-road assessors for joint decision making of fitness to drive in dementia.
PMID- 27496015
TI - Anti-inflammatory activity of aqueous extract and bioactive compounds identified
from the fruits of Hancornia speciosa Gomes (Apocynaceae).
AB - BACKGROUND: Hancornia speciosa Gomes (Apocynaceae), popularly known as
"mangabeira," has been used in folk medicine to treat inflammatory disorders,
hypertension, dermatitis, diabetes, liver diseases and gastric disorders.
Although the ethnobotany indicates that its fruits can be used for the treatment
of ulcers and inflammatory disorders, only few studies have been conducted to
prove such biological activities. This study investigated the anti-inflammatory
properties of the aqueous extract of the fruits of H. speciosa Gomes as well as
its bioactive compounds using in vivo experimental models. METHODS: The bioactive
compounds were identified by High Performance Liquid Chromatography coupled with
diode array detector (HPLC-DAD) and Liquid Chromatography coupled with Mass
Spectrometry (LC-MS). The anti-inflammatory properties were investigated through
in vivo tests, which comprised xylene-induced ear edema, carrageenan-induced
peritonitis and zymosan-induced air pouch. The levels of IL-1beta, IL-6, IL-12
and TNF-alpha were determined using ELISA. RESULTS: Rutin and chlorogenic acid
were identified in the extract as the main secondary metabolites. In addition,
the extract as well as rutin and chlorogenic acid significantly inhibited the
xilol-induced ear edema and also reduced the cell migration in both carrageenan
induced peritonitis and zymosan-induced air pouch models. Reduced levels of
cytokines were also observed. CONCLUSION: This is the first study that
demonstrated the anti-inflammatory activity of the extract of H. speciosa fruits
against different inflammatory agents in animal models, suggesting that its
bioactive molecules, especially rutin and chlorogenic acid are, at least in part,
responsible for such activity. These findings support the widespread use of
Hancornia speciosa in popular medicine and demonstrate that its aqueous extract
has therapeutical potential for the development of herbal drugs with anti
inflammatory properties.
PMID- 27496017
TI - Reply to "Comment on: MALDI ionization mechanisms investigated by comparison of
isomers of dihydroxybenzoic acid".
PMID- 27496016
TI - Effects of dietary postbiotic and inulin on growth performance, IGF1 and GHR mRNA
expression, faecal microbiota and volatile fatty acids in broilers.
AB - BACKGROUND: Postbiotics (metabolic products by lactic acid bacteria) and
prebiotics have been established as substitute to antibiotics in order to enhance
immunity and growth performance in broiler chickens. Nonetheless, insufficient
information is available on the effects of postbiotics and prebiotics combination
on growth performance, faecal microbiota, pH and volatile fatty acids (VFA), as
well as liver insulin like growth factor 1 (IGF1) and growth hormone receptor
(GHR) mRNA expressions in broiler chickens. The aim of this experiment was to
evaluate the effects of different types of postbiotics with different levels of
prebiotic (inulin) on broiler for those parameters. RESULTS: The results showed
that birds fed T3: (0.3 % RI11 + 0.8 % Inulin), T4: (0.3 % RI11 + 1.0 % Inulin),
and T6: (0.3 % RG14+ 1.0 % Inulin) had higher (p < 0.05) final body weight (BW)
and total weight gain (WG) than other treatments. Birds fed T3 had lower feed
conversion ratio (FCR) which was significantly different from those fed with
negative control diet but was similar to other treatments. Postbiotic and inulin
increased (p < 0.05) faecal lactic acid bacteria (LAB) and reduced (p < 0.05)
Enterobacteriaceae count. Birds fed T4 and T6 had higher faecal acetic acid and
propionic acid respectively, and both had higher total VFA and lactic acid
bacteria but lower pH and Enterobacteriaceae (ENT) counts compared to other
treatments. The liver of birds fed T4 and T6 had higher IGF1 expression compared
to other treatments while T6 had higher GHR mRNA expression compared to other
treatments. CONCLUSIONS: Results indicate that the addition of postbiotics and
inulin combinations had beneficial effects on total BW, feed efficiency, mucosa
architecture and IGF1 and GHR mRNA expression in broiler chickens.
PMID- 27496018
TI - Tigecycline-based versus sulbactam-based treatment for pneumonia involving
multidrug-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex.
AB - BACKGROUND: The treatment options for pneumonia involving multidrug-resistant
Acinetobacter calcoaceticus-Acinetobacter baumannii (MDR Acb) complex are
limited, and the optimal treatment has not been established. METHODS: To compare
the efficacy of tigecycline-based with sulbactam (or ampicillin/sulbactam)-based
therapy for pneumonia involving MDR Acb complex, we conducted a retrospective
study comparing 84 tigecycline-treated adult patients during the period August
2007 to March 2010 with 84 sulbactam or ampicillin/sulbactam-treated adult
patients during the period September 2004 to July 2007. Both groups had the
matched Acute Physiology and Chronic Health Evaluation (APACHE) II score and
received treatment for at least 7 days. RESULTS: The mean APACHE II score was
20.1 for both groups. More patients in sulbactam group had ventilator use (89.3 %
versus 69.0 %), bilateral pneumonia (79.8 % versus 60.7 %) and combination
therapy (84.5 % versus 53.6 %), particularly with carbapenems (71.4 % versus 6.0
%), while more patients in tigecycline group had delayed treatment (41.7 % versus
26.2 %) (P <0.05). At the end of treatment, more patients in sulbactam group had
airway MDR Acb complex eradication (63.5 % versus 33.3 %, P <0.05). The clinical
resolution rate was 66.7 % for both groups. The mortality rate during treatment
was 17.9 % in sulbactam group, and 25.0 % in tigecycline group (P = 0.259). The
multivariate analysis showed that bilateral pneumonia was the only independent
predictor for mortality during treatment (adjusted odds ratio, 2.717; 95 %
confidence interval, 1.015 to 7.272). CONCLUSIONS: Patients treated with either
tigecycline-based or sulbactam-based therapy had a similar clinical outcome, but
tigecycline group had a lower microbiological eradiation rate.
PMID- 27496019
TI - Elucidating Combinatorial Chromatin States at Single-Nucleosome Resolution.
AB - Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has been
instrumental to our current view of chromatin structure and function. It allows
genome-wide mapping of histone marks, which demarcate biologically relevant
domains. However, ChIP-seq is an ensemble measurement reporting the average
occupancy of individual marks in a cell population. Consequently, our
understanding of the combinatorial nature of chromatin states relies almost
exclusively on correlation between the genomic distributions of individual marks.
Here, we report the development of combinatorial-iChIP to determine the genome
wide co-occurrence of histone marks at single-nucleosome resolution. By comparing
to a null model, we show that certain combinations of overlapping marks (H3K36me3
and H3K79me3) co-occur more frequently than would be expected by chance, while
others (H3K4me3 and H3K36me3) do not, reflecting differences in the underlying
chromatin pathways. We further use combinatorial-iChIP to illuminate aspects of
the Set2-RPD3S pathway. This approach promises to improve our understanding of
the combinatorial complexity of chromatin.
PMID- 27496021
TI - Selective 5-aminolevulinic acid-induced protoporphyrin IX fluorescence in
Gliomas.
AB - Malignant gliomas are locally invasive tumors that offer a poor prognosis.
Evidence shows that complete resection of the tumor at the time of surgery
confers a significant improvement in overall survival. In recent years, 5-
aminolevulinic acid (ALA)-induced fluorescence has been used by neurosurgeons to
good effect in increasing the rate of complete resection. Despite the
considerable interest in the use of 5-ALA in fluorescence-guided neurosurgery,
the mechanisms behind the accumulation of Protoporphyrin IX (PpIX) in neoplastic
tissue are unclear. In this review, we summarize the evidence in the literature
on the mechanisms underlying the selective production of PpIX with a specific
focus on gliomas.
PMID- 27496020
TI - Does home equipment contribute to socioeconomic gradients in Australian
children's physical activity, sedentary time and screen time?
AB - BACKGROUND: Activity behaviours (physical activity, sedentary time and screen
time) have been linked to health outcomes in childhood. Furthermore,
socioeconomic disparities have been observed in both children's activity
behaviours and health outcomes. Children's physical home environments may play a
role in these relationships. This study aimed to examine the associations and
interactions between children's physical home environment, socioeconomic status
and moderate-to-vigorous physical activity, sedentary time and screen time.
METHODS: Australian children (n = 528) aged 9-11 years from randomly selected
schools participated in the cross-sectional International Study of Childhood
Obesity, Lifestyle and the Environment. Children's physical home environment
(access to equipment), socioeconomic status (household income and parental
education) and demographic variables (gender and family structure) were
determined by parental questionnaire. Moderate-to-vigorous physical activity and
sedentary time were measured objectively by 7-day 24-h accelerometry. Screen time
was obtained from child survey. The associations between the physical home
environment, socioeconomic status and moderate-to-vigorous physical activity,
sedentary time and screen time were examined for 427 children, using analysis of
covariance, and linear and logistic regression, with adjustment for gender and
family structure. RESULTS: The presence of TVs (p < 0.01) and video game consoles
(p < 0.01) in children's bedrooms, and child possession of handheld video games
(p = 0.04), cell phones (p < 0.01) and music devices (p = 0.04) was significantly
and positively associated with screen time. Ownership of these devices (with the
exception of music devices) was inversely related to socioeconomic status
(parental education). Children's moderate-to-vigorous intensity physical activity
(p = 0.04) and possession of active play equipment (p = 0.04) were both
positively associated with socioeconomic status (household income), but were not
related to each other (with the exception of bicycle ownership). CONCLUSIONS:
Children with less electronic devices, particularly in their bedrooms,
participated in less screen time, regardless of socioeconomic status.
Socioeconomic disparities were identified in children's moderate-to-vigorous
physical activity, however socioeconomic status was inconsistently related to
possession of active play equipment. Home active play equipment was therefore not
a clear contributor to the socioeconomic gradients in Australian children's
moderate-to-vigorous physical activity.
PMID- 27496022
TI - Development of a video-assisted thoracoscopic lobectomy program in a single
institution: results before and after completion of the learning curve.
AB - BACKGROUND: The development of a video assisted thoracic surgery lobectomy (VATS
L) program provides a dedicated surgical team with a recognized learning curve
(LC) of 50 procedures. We analyse the results of our program, comparing the LC
with subsequent cases. METHODS: From June 2012 to March 2015, we performed n =
146 VATS major pulmonary resections: n = 50 (Group A: LC); n = 96 (Group B). Pre
operative mediastinal staging followed the National Comprehensive Cancer Network
guidelines. All procedures were performed using a standard anterior approach to
the hilum; lymphadenectomy followed the NCCN recommendations. During the LC, VATS
L indication was reserved to clinical stages I, therefore evaluated case by case.
RESULTS: Mean operative time was 191 min (120-290) in Group A and 162 min (85
360) in Group B (p <0,01). Pathological T status was similar between two Groups.
Lymphadenectomy included a mean of 5.8 stations in Group A and 6.6 in Group B
resulting in: pN0 disease: Group A n = 44 (88 %), Group B n = 80 (83.4 %); pN1:
Group A n = 3 (6 %), Group B n = 8 (8.3 %); pN2: Group A n = 3 (6 %), Group B n =
8 (8.3 %). Conversion rate was: 8 % in group A (n = 4 vascular injuries); 1.1 %
in Group B (n = 1 hilar lymph node disease). We registered n = 6 (12 %)
complications in Group A, n = 10 (10.6 %) in Group B. One case (1.1 %) of late
post-operative mortality (90 days) was registered in Group B for liver failure.
Mean hospital stay was 6.5 days in Group A and 5.9 days in Group B. CONCLUSIONS:
We confirm the effectiveness of a VATS-L program with a learning curve of 50
cases performed by a dedicated surgical team. Besides the LC, conversion rate
falls down, lymphadenectomy become more efficient, indications can be extended to
upper stages.
PMID- 27496023
TI - Mid-term oncologic outcome of a novel approach for locally advanced colon cancer
with neoadjuvant chemotherapy and surgery.
AB - PURPOSE: Neoadjuvant chemotherapy is being actively tested as an emerging
alternative for the treatment of locally advanced colon cancer (LACC) patients,
resembling its use in other gastrointestinal tumors. This study assesses the mid
term oncologic outcome of LACC patients treated with oxaliplatin and
fluoropyrimidines-based preoperative chemotherapy followed by surgery. METHODS
AND PATIENTS: Patients with radiologically resectable LACC treated with
neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed.
Radiological, metabolic, and pathological tumor response was assessed. Both
postoperative complications, relapse-free survival (RFS), and overall survival
(OS) were studied. RESULTS: Sixty-five LACC patients who received treatment were
included. Planned treatment was completed by 93.8 % of patients. All patients
underwent surgery without delay. The median time between the start of
chemotherapy and surgery was 71 days (65-82). No progressive disease was observed
during preoperative treatment. A statistically significant tumor volume reduction
of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a
median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake
Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of
patients. Postoperative complications were observed in 15.4 % of patients, with
no cases of mortality. After a median follow-up of 40.1 months, (p 25-p 75: 27.3
57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial
OS was 95.3 %. CONCLUSION: Preoperative chemotherapy in LACC patients is safe and
able to induce major tumor regression. Survival times are encouraging, and
further research seems warranted.
PMID- 27496025
TI - Two scenes or not two scenes: The effects of stimulus repetition and view
similarity on scene categorization from brief displays.
AB - Previous research suggests that understanding the gist of a scene relies on
global structural cues that enable rapid scene categorization. This study used a
repetition blindness (RB) paradigm to interrogate the nature of the scene
representations used in such rapid categorization. When stimuli are repeated in a
rapid serial visual presentation (RSVP) sequence (~10 items/sec), the second
occurrence of the repeated item frequently goes unnoticed, a phenomenon that is
attributed to a failure to consolidate two conscious episodes (tokens) for a
repeatedly activated type. We tested whether RB occurs for different exemplars of
the same scene category, which share conceptual and broad structural properties,
as well as for identical and mirror-reflected repetitions of the same scene,
which additionally share the same local visual details. Across 2 experiments,
identical and mirror-image scenes consistently produced a repetition
facilitation, rather than RB. There was no convincing evidence of either RB or
repetition facilitation for different members of a scene category. These findings
indicate that in the first 100-150 ms of processing scenes are represented in
terms of local visual features, rather than more abstract category-general
features, and that, unlike other kinds of stimuli (words or objects), scenes are
not susceptible to token individuation failure.
PMID- 27496024
TI - Tracking the emergence of memories: A category-learning paradigm to explore
schema-driven recognition.
AB - Previous research has shown that prior knowledge structures or schemas affect
recognition memory. However, since the acquisition of schemas occurs over
prolonged periods of time, few paradigms allow the direct manipulation of schema
acquisition to study their effect on memory performance. Recently, a number of
parallelisms in recognition memory between studies involving schemas and studies
involving category learning have been identified. The current paper capitalizes
on these findings and offers a novel experimental paradigm that allows
manipulation of category learning between individuals to study the effects of
schema acquisition on recognition. First, participants learn to categorize
computer-generated items whose category-inclusion criteria differ between
participants. Next, participants study items that belong to either the learned
category, the non-learned category, both, or neither. Finally, participants
receive a recognition test that includes old and new items, either from the
learned, the non-learned, or neither category. Using variations on this paradigm,
four experiments were conducted. The results from the first three studies suggest
that learning a category increases hit rates for old category-consistent items
and false alarm rates for new category-consistent lures. Absent the category
learning, no such effects are evident, even when participants are exposed to the
same learning trials as those who learned the categories. The results from the
fourth experiment suggest that, at least for false alarm rates, the effects of
category learning are not solely attributable to frequency of occurrence of
category-consistent items during learning. Implications for recognition memory as
well as advantages of the proposed paradigm are discussed.
PMID- 27496026
TI - Authors' reply to Bosco-Levy and Salvo.
PMID- 27496027
TI - The role of primary care in improving health equity: report of a workshop held by
the WONCA Health Equity Special Interest Group at the 2015 WONCA Europe
Conference in Istanbul, Turkey.
AB - The WONCA Special Interest Group on Health Equity was established in 2014 to
provide a focus of support, education, research and policy on issues relating to
promotion of health equity in primary care settings. In keeping with this remit,
the group hosted a workshop at the WONCA Europe conference held in Istanbul in
October 2015. The aim of the session was to engage practitioners from across
Europe in discussion of the barriers and facilitators to addressing the social
determinants of health at practice level and in the training of doctors. This
commentary reflects on the main findings from this workshop and how these compare
with existing work in this field.
PMID- 27496028
TI - Antiproliferative Effects of Modified Bioflavonoid in Ex Vivo Model.
AB - We studied the effect of modified bioflavonoid and reference drug quercetin
dihydrate on proliferation of mononuclears triggered by T- and B-cell mitogens.
Lymphocytes were in vivo pretreated with the examined agents followed by their
explantation and in vitro activation with T- and B-cell mitogens in cell culture.
Intraperitoneal injection of modified bioflavonoid and quercetin dihydrate
produced a dose-dependent inhibition of proliferation of the in vitroactivated
splenocytes; modified bioflavonoid demonstrated higher antiproliferative
activity.
PMID- 27496029
TI - Serological Analysis of Immunogenic Properties of Recombinant Meningococcus IgA1
Protease-Based Proteins.
AB - Using the genome sequence of IgA1 protease of N. meningitidis of serogroup B,
four recombinant proteins of different structure and molecular weight were
constructed. These proteins were equal in inducing the formation of specific
antibodies to IgA1 protease and had protective properties against meningococci.
In the sera of immunized mice, anti-IgA1 protease antibodies were detected by
whole-cell ELISA, which indicated the presence of IgA1 protease on the surface of
these bacteria. We hypothesized that the protective properties of IgA1 protease
based antigens and IgA1 protease analogs could be realized not only via
impairment of bacterium adhesion to the mucosa, but also via suppression of this
pathogen in the organism. The presented findings seem promising for using these
proteins as the basis for anti-meningococcus vaccine.
PMID- 27496030
TI - Effect of Fluoxetine on Neurogenesis in Hippocampal Dentate Gyrus after Global
Transient Cerebral Ischemia in Rats.
AB - Changes in cerebral neurogenesis provoked by ischemia and the effect of
fluoxetine on this process were studied using a three-vessel occlusion model of
global transient cerebral ischemia. The global transient cerebral ischemia was
modeled on male Wistar rats by transient occlusion of three major vessels
originating from the aortic arch and supplying the brain (brachiocephalic trunk,
left subclavian artery, and left common carotid artery). The cells expressing
doublecortin (DCX, a marker of young neurons) were counted in the hippocampal
dentate gyrus on day 31 after ischemia modeling. It was found that ischemia
inhibited neurogenesis in the dentate gyrus in comparison with sham-operated
controls (p<0.05), while fluoxetine (20 mg/kg/day) injected over 10 days after
surgery restored neurogenesis to the control level (p<0.001).
PMID- 27496031
TI - Physiological Features of Perigonadal Adipose Tissue Containing Uncoupling
Protein UCP1 in ICR Mice.
AB - Immunoreactive uncoupling protein UCP1 was found in the perigonadal fat of only
twothirds of 14-week-old male ICR mice. The presence of UCP1 had no effect on the
rate of O2 consumption by the adipose tissue. The cellularity of perigonadal fat
estimated by the DNA content was significantly higher in tissue containing UCP1
than in samples without this protein. This regularity was also observed after
adaptation of mice to moderate cold (10oC) over 8 weeks.
PMID- 27496032
TI - Expression of Cytokine Genes and Growth Factors in Rat Lungs and Kidneys after
Subtotal Hepatectomy.
AB - Expression of il1b, il6, il10, tnfa, hgf, tgfb, vegf, and fgf2 genes in the lungs
and kidneys was examined on rat model of liver regeneration after subtotal
hepatectomy. Enhanced expression of il6, il10, tnfa, hgf, and fgf2 genes was
detected at the early terms after 80% liver resection.
PMID- 27496033
TI - Oxidative Stress and Catalase Gene.
AB - We studied the frequency of alleles and genotypes of CAT gene -262C>T
polymorphism (rs1001179) in Russian and Buryat adolescents. The frequency of
262T allele was 28.31% in Russians and 16.84% in Buryats (p<0.01). In both ethnic
groups, a correlation between the study polymorphism and concentration of diene
conjugates was observed. Carriers of TT-genotype of CAT gene-262C>T polymorphism
had lower level of diene conjugates than carriers of CT- and CC-genotypes.
PMID- 27496034
TI - Clinical Morphological Studies of Myelofibrosis with Different Types of Bone
Marrow Involvement in Patients with Chronic Lymphocytic Leukemia.
AB - Clinical-morphological study of myelofibrosis was carried out in patients with
chronic lymphocytic leukemia at the debut of the disease. Trephinobiopsy
specimens of the ileac bone, aspirated specimens of the bone marrow, and
peripheral blood smears were studied in 80 patients. Chronic lymphocytic leukemia
was associated with myelofibrosis of different severity in 22.5% cases.
Morphometric analysis of trephinobiopsy specimens showed that the severity
(histology and dissemination) of myelofibrosis correlated with the type of tumor
involvement of the bone marrow. Focal tumor involvement of the bone marrow
predominated in trephinobiopsy specimens from patients without myelofibrosis,
while patients with myelofibrosis developed mainly diffuse tumor infiltration,
associated with the greatest dissemination of the initial and manifest
myelofibrosis. No myelofibrosis was found in patients with interstitial tumor
involvement of the bone marrow. The severity of the initial and manifest
myelofibrosis directly correlated with the tumor involvement of the bone marrow
and peripheral blood. Evaluation of the prognosis showed that initial
myelofibrosis was associated with disease standing of 5.5 months, while manifest
condition with a disease of 8.5 months and longer.
PMID- 27496035
TI - Relationship between Morphofunctional Changes in Open Traumatic Brain Injury and
the Severity of Brain Damage in Rats.
AB - A correlation between the severity of morphofunctional disturbances and the
volume of brain tissue injury determined by MRT was demonstrated on the model of
open traumatic brain injury in rats. A relationship between the studied
parameters (limb placing and beam walking tests and histological changes) and
impact force (the height of load fell onto exposed brain surface) was revealed.
PMID- 27496036
TI - Experimental Evaluation of Biodegradable Film Compositions Based on Gelatin with
Colchicine.
AB - Biodegradable film compositions based on natural biopolymer gelatin with
immobilized colchicine were prepared and their efficiency in prevention of the
adhesion process in the pericardium was evaluated on rabbit model of
postoperative pericarditis. The use of gelatin-based biodegradable film
compositions significantly reduced the intensity of adhesion formation in the
pericardial cavity, while immobilization of anti-inflammatory drug colchicine
amplified their anti-adhesion activity.
PMID- 27496037
TI - Effect of Circulation Parameters on Functional Status of HepaRG Spheroids
Cultured in Microbioreactor.
AB - We studied the relationship between microcirculation parameters and functional
status of HepaRG cells in spheroids and chose an optimal regimen within the
physiologically permissible limits of mechanical impact for the cells that
maintains the expression of functional genes of the liver.
PMID- 27496038
TI - Involvement of Protein Kinase C-delta in the Realization of Cardioprotective
Effect of Ischemic Postconditioning.
AB - Experiments on isolated perfused rat heart modeled 45-min global ischemia
followed by 30-min reperfusion. Ischemic postconditioning was modeled by 3 cycles
of reperfusion (30 sec) and ischemia (30 sec). Cardiomyocyte necrosis was
assessed by the level of creatine phosphokinase in the perfusate.
Postconditioning reduced the release of creatine phosphokinase from the heart by
30%. The cardioprotective effect of ischemic postconditioning was eliminated
after inhibition of protein kinase C with cheleritrin or after blockade of delta
isoform of protein kinase C with rottlerin. These findings attest to
participation of protein kinase C-delta in the realization of the
cardioprotective effect of postconditioning.
PMID- 27496040
TI - Prognostic Value of the Cumulative Cisplatin Dose During Concurrent
Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A
Secondary Analysis of a Prospective Phase III Clinical Trial.
AB - BACKGROUND: The objective of this study was to evaluate the prognostic value of
the cumulative cisplatin dose (CCD) for long-term survival outcomes after
concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal
carcinoma (NPC). METHODS: Patients were included in an open-label phase III
multicenter randomized controlled trial performed at seven institutions in China,
and the 298 patients receiving CCRT only were assessed. Patient survival between
different CCD groups were compared. RESULTS: Median CCD for the 298 patients was
240 mg/m2 (range, 40-320 mg/m2); 113 (37.9%) patients received a CCD of <240
(<=200) mg/m2, and 185 (62.1%) received a CCD of >=240 mg/m2. For CCD of >=240
mg/m2 vs. <240 mg/m2, the estimated 5-year overall survival, disease-free
survival, locoregional relapse-free survival, and distant metastasis-free
survival rates were 83.2% vs. 76.2% (p = .403), 73.5% vs. 67.8% (p = .461), 90.4%
vs. 86.8% (p = .551), and 82.6% vs. 79.7% (p = .632), respectively. Multivariate
analysis demonstrated that CCD (240 mg/m2) was not an independent prognostic
factor in either the entire cohort or stage III/IV subgroup. CONCLUSION: A CCD of
>=240 mg/m2 was not an independent prognostic factor in patients with
locoregionally advanced NPC at high risk of distant metastasis, and 200 mg/m2
cisplatin may be adequate to achieve a survival benefit. IMPLICATIONS FOR
PRACTICE: The current standard treatment for locoregionally advanced
nasopharyngeal carcinoma (NPC) is cisplatin-based concurrent chemoradiotherapy
(CCRT), and the cisplatin is delivered every 3 weeks (100 mg/m2) for three
cycles. However, the prognostic value of cumulative cisplatin dose (CCD)
delivered during CCRT is controversial. The present study investigated the
prognostic value of CCD and demonstrated that a CCD of 200 mg/m2 during CCRT is
adequate to achieve satisfactory survival outcomes for patients with
locoregionally advanced NPC. This finding is of great importance to clinicians
because it could allow patients to avoid excessive treatment and toxicities.
PMID- 27496039
TI - Preventing and Managing Toxicities of High-Dose Methotrexate.
AB - : : High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is
used to treat a range of adult and childhood cancers. Although HDMTX is safely
administered to most patients, it can cause significant toxicity, including acute
kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from
crystallization of methotrexate in the renal tubular lumen, leading to tubular
toxicity. AKI and other toxicities of high-dose methotrexate can lead to
significant morbidity, treatment delays, and diminished renal function. Risk
factors for methotrexate-associated toxicity include a history of renal
dysfunction, volume depletion, acidic urine, and drug interactions. Renal
toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic
concentrations, which further worsen renal function and exacerbate nonrenal
adverse events, including myelosuppression, mucositis, dermatologic toxicity, and
hepatotoxicity. Serum creatinine, urine output, and serum methotrexate
concentration are monitored to assess renal clearance, with concurrent hydration,
urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and
subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite
preventive strategies, increased hydration, high-dose leucovorin, and
glucarpidase are usually sufficient to allow renal recovery without the need for
dialysis. Prompt recognition and effective treatment of AKI and associated
toxicities mitigate further toxicity, facilitate renal recovery, and permit
patients to receive other chemotherapy or resume HDMTX therapy when additional
courses are indicated. IMPLICATIONS FOR PRACTICE: High-dose methotrexate (HDMTX),
defined as a dose higher than 500 mg/m2, is used for a range of cancers. Although
HDMTX is safely administered to most patients, it can cause significant toxicity,
including acute kidney injury (AKI), attributable to crystallization of
methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI
occurs despite preventive strategies, increased hydration, high-dose leucovorin,
and glucarpidase allow renal recovery without the need for dialysis. This
article, based on a review of the current associated literature, provides
comprehensive recommendations for prevention of toxicity and, when necessary,
detailed treatment guidance to mitigate AKI and subsequent toxicity.
PMID- 27496041
TI - The Association Between Body Size and Breast Cancer in Han Women in Northern and
Eastern China.
AB - INTRODUCTION: Although obesity has been reported worldwide as a risk factor for
breast cancer, there are still some inconsistencies regarding the association
between obesity and breast cancer. Body mass index (BMI) is used most to assess
the extent of obesity; however, the association of other body size
characteristics, such as waist and hip circumference, with susceptibility to
breast cancer in Chinese Han women needs to be better assessed. PATIENTS AND
METHODS: Female Chinese Han patients (N = 2,800) were recruited from 21 hospitals
in northern and eastern China from April 2012 to April 2013 for a case-control
study. The significant differences of factors related to body size between the
breast-cancer case and control groups were determined by Student's t test and chi
square tests. RESULTS: Premenopausal women with breast cancer had higher BMI and
larger waist and hip circumferences (p = 2 * 10-4, <1 * 10-6, and 2 * 10-5,
respectively). However, these body-size factors were not associated with
postmenopausal breast cancer (p = .45, 0.32, and 0.12, respectively). BMI between
28 and 30 kg/m2 or greater than 32 kg/m2 was related to breast cancer incidence
in the overall study population and in premenopausal women but not in the
postmenopausal group. CONCLUSION: Obesity is significantly associated with breast
cancer in Chinese Han premenopausal women but not in postmenopausal women. Thus,
it is important to realize that weight control, as well as avoiding abdominal
obesity, should be considered as one of the most effective methods of reducing
breast cancer risk. IMPLICATIONS FOR PRACTICE: To better understand the
characteristics and risk factors for breast cancer in Han women in northern and
eastern China, a case-control study of 2,800 Chinese Han women was conducted.
Obesity was significantly associated with breast cancer in Chinese Han
premenopausal women but not in postmenopausal women. Consequently, controlling
body weight and avoiding abdominal obesity should be considered as one of the
most effective methods of reducing breast cancer susceptibility. However, the
diversity between this study's finding among Chinese Han women and other data
previously reported among European and American populations still needs further
investigation.
PMID- 27496042
TI - The Neurotoxic TAU45-230 Fragment Accumulates in Upper and Lower Motor Neurons in
Amyotrophic Lateral Sclerosis Subjects.
AB - Amyotrophic lateral sclerosis (ALS) is a progressive and lethal neurodegenerative
disease characterized by the loss of upper and lower motor neurons leading to
muscle paralysis in affected individuals. Numerous mechanisms have been
implicated in the death of these neurons. However, the pathobiology of this
disease has not been completely elucidated. In the present study, we investigated
to what extent tau cleavage and the generation of the neurotoxic tau45-230
fragment is associated with ALS. Quantitative Western blot analysis indicated
that high levels of tau45-230 accumulated in lumbar and cervical spinal cord
specimens obtained from ALS subjects. This neurotoxic tau fragment was also
detected in ALS upper motor neurons located in the precentral gyrus. Our results
also showed that tau45-230 aggregates were present in the spinal cord of ALS
patients. On the other hand, this neurotoxic fragment was not generated in a
mouse model of a familial form of this disease. Together, these results suggest a
potential role for this neurotoxic tau fragment in the mechanisms leading to the
degeneration of motor neurons in the context of sporadic ALS.
PMID- 27496044
TI - The autosomal genetic control of sexually dimorphic traits in humans is largely
the same across the sexes.
AB - There are substantial phenotypic differences between the male and female human.
Several complex traits have recently been tested to see whether these phenotypic
differences are explained by differences in genetic control between males and
females. While some differences in genetic control between males and females are
detected, overall the results demonstrate that the genetic control of complex
traits in humans is largely the same across the sexes.Please see related Research
article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1025
x.
PMID- 27496043
TI - Vaccination sequence effects on immunological response and tissue bacterial
burden in paratuberculosis infection in a rabbit model.
AB - Paratuberculosis (PTB), a chronic granulomatous enteritis produced by
Mycobacterium avium subspecies paratuberculosis (MAP), is considered as one of
the diseases with the highest economic impact in the ruminant industry.
Vaccination against MAP is recommended during the first months after birth on the
basis that protection would be conferred before the first contact with
mycobacteria. However, little is known about the therapeutic effect of MAP
vaccination in controlled experimental conditions. The current study was designed
to evaluate the efficacy of vaccination before and after challenge with MAP in a
rabbit infection model. The rabbits were divided into four groups: non-infected
control (NIC, n = 4), infected control challenged with MAP (IC, n = 5),
vaccinated and challenged 1 month after with MAP (VSI, n = 5) and challenged with
MAP and vaccinated 2 months later (IVS, n = 5). The results from this study show
a quick increase in IFN-gamma release upon stimulation with bovine, avian and
johnin PPD in animals vaccinated before MAP challenge. All vaccinated animals
show an increased humoral response as seen by western blot and ELISA. The final
bacteriology index (considering tissue culture and qPCR) shows that the IC group
was the most affected. Vaccination after infection (IVS) produced the lowest
bacteriology index showing significant differences with the IC group (p = 0.034).
In conclusion, vaccination against MAP shows positive effects in a rabbit model.
However, vaccination after infection shows a slightly stronger protective effect
compared to vaccination before infection, suggesting a therapeutic effect. This
feature could be applied to previously infected adult animals under field
conditions.
PMID- 27496045
TI - Connecting Professional Practice and Technology at the Bedside: Nurses' Beliefs
about Using an Electronic Health Record and Their Ability to Incorporate
Professional and Patient-Centered Nursing Activities in Patient Care.
AB - The purpose of this research is to determine the effects of implementing an
electronic health record on medical-surgical registered nurses' time spent in
direct professional patient-centered nursing activities, attitudes and beliefs
related to implementation, and changes in level of nursing engagement after
deployment of the electronic health record. Patient-centered activities were
categorized using Watson's Caritas Processes and the Relationship-Based Care
Delivery System. Methods included use of an Attitudes and Beliefs Assessment
Questionnaire, Nursing Engagement Questionnaire, and Rapid Modeling Corporation's
personal digital assistants for time and motion data collection. There was a
significant difference in normative belief between nurses with less than 15
years' experience and nurses with more than 15 years' experience (t21 = 2.7, P =
.01). While nurses spent less time at the nurses' station, less time charting,
significantly more time in patients' rooms and in purposeful interactions, time
spent in relationship-based caring behavior categories actually decreased in most
categories. Nurses' engagement scores did not significantly increase. These
results serve to inform healthcare organizations about potential factors related
to electronic health record deployment which create shifts in nursing time spent
across care categories and can be used to explore further patient centered care
practices.
PMID- 27496046
TI - Study protocol for Norwegian Psychomotor Physiotherapy versus Cognitive Patient
Education in combination with active individualized physiotherapy in patients
with long-lasting musculoskeletal pain - a randomized controlled trial.
AB - BACKGROUND: Norwegian Psychomotor Physiotherapy (NPMP) has been an established
treatment approach for more than 50 years, although mostly in the Scandinavian
countries, and is usually applied to patients with widespread and long-lasting
musculoskeletal pain and/or psychosomatic disorders. Few studies have been
investigating outcome of NPMP and no randomized clinical trials (RCT) have been
systematically tried out on individuals. METHODS/DESIGN: This is a study protocol
for a pragmatic, single blinded RCT, which will take place in a city of Norway.
The participants will be block randomized either to receive NPMP or Cognitive
Patient Education in combination with active individualized physiotherapy (COPE
PT). The intervention will reflect usual care and will be conducted in
physiotherapy clinics by five experienced physiotherapists in each of the two
treatment approaches. DISCUSSION: The findings of the present study may give an
important contribution to our knowledge of the outcome of NPMP, on patients with
long-lasting widespread musculoskeletal pain and/or pain located to the neck and
shoulder region. TRIAL REGISTRATION: The study has been registered with
ClinicalTrials.gov (June 9 th 2015, NCT02482792).
PMID- 27496047
TI - Investigation of recrystallization of amorphous trehalose through hot-humidity
stage X-ray powder diffraction.
AB - The aim of this work was an investigation of the physical changes of the
amorphous model material spray-dried trehalose through the use of various
analytical techniques and to identify a suitable, rapid method able to quantify
the changes. The crystallinity changes and recrystallization process of amorphous
samples were investigated by hot-humidity stage X-ray powder diffractometry (HH
XRPD) with fresh samples, conventional X-ray powder diffractometry (XRPD) used
stored samples and by differential scanning calorimetry (DSC). The data from the
three methods were compared and the various forms of trehalose were analysed. HH
XRPD demonstrated that the recrystallization began at 40 and 60 degrees C up to
45% RH and at 70 degrees C up to 30% RH into dihydrate form. At 70 degrees C up
to 60% RH the anhydrous form of trehalose appeared too. Conventional XRPD results
showed, that in the 28days stored samples the dihydrate form was detected at 40
degrees C, 50% RH. Storage at 60 degrees C, 40% RH resulted in the appearance of
the anhydrous form and at 60 degrees C, 50% RH both polymorphic forms were
detected. By carrying out the DSC measurements at different temperatures the
fraction of recrystallized trehalose dihydrate was detected. The
recrystallization investigated by HH-XRPD and DSC followed Avrami kinetics, the
calculated rate constants of isothermal crystallization (K) were same. Both HH
XRPD and conventional XRPD was suitable for the detection of the physical changes
of the amorphous model material. DSC measurements showed similar results as HH
XRPD. Primarily HH-XRPD could be suggested for prediction, because the method is
fast and every changes could be studied on one sample.
PMID- 27496048
TI - Biopharmaceutic classification of drugs revisited.
AB - The biopharmaceutics classification system (BCS) was based on the tube model of
the intestinal lumen. This model considers constant drug permeability along the
intestines, a plug flow fluid with the suspended drug particles moving with the
fluid, and dissolution in the small particle limit. Since then the research work
focusing on drug gastrointestinal (GI) absorption phenomena and processes rely on
the classical laws of transport, diffusion and kinetics; however, the homogeneous
assumptions associated with the well-stirred Euclidean media, where the classical
laws of diffusion and kinetics apply, have been questioned in the past. In this
work we explore the biopharmaceutic classification of drugs using a heterogeneous
pseudo steady-state model of oral drug absorption. The fraction of dose absorbed
(Fabs) was expressed as a function of two time-dependent processes where time
dependent coefficients govern drug absorption and non-absorption processes.
Fundamental drug properties like the absorption potential are correlated with
Fabs and allow the biopharmaceutic classification of drugs taking into account
the heterogeneous aspects of oral drug absorption. This analysis reveals that for
Class I drugs no time dependency is expected for both absorption and non
absorption processes since the gastric emptying is controlling the absorption of
Class I drugs while the completion of absorption (Fabs>90%) is terminated along
the first part of the jejunum. Due to the biopharmaceutical properties of Class
II, III and IV drugs, these drugs travel throughout the GI tract and therefore
both absorption and non absorption processes will exhibit time dependency. Thus,
the calculation of Fabs (<90%) for Class II, III and IV is dependent on the
estimates of the time exponents of time dependent coefficients controlling drug
absorption e.g. dissolution, uptake or non absorption e.g. precipitation.
PMID- 27496049
TI - Formulation and dissolution kinetics study of hydrophilic matrix tablets with
tramadol hydrochloride and different co-processed dry binders.
AB - The aim of this study is to present the possibility of using of co-processed dry
binders for formulation of matrix tablets with drug controlled release.
Hydrophilic matrix tablets with tramadol hydrochloride, hypromellose and
different co-processed dry binders were prepared by direct compression method.
Hypromelloses MethocelTM K4M Premium CR or MethocelTM K100M Premium CR were used
as controlled release agents and Prosolv(r) SMCC 90 or DisintequikTM MCC 25 were
used as co-processed dry binders. Homogeneity of the tablets was evaluated using
scanning electron microscopy and energy dispersive X-ray microanalysis. The
release of tramadol hydrochloride from prepared formulations was studied by
dissolution test method. The dissolution profiles obtained were evaluated by non
linear regression analysis, release rate constants and other kinetic parameters
were determined. It was found that matrix tablets based on Prosolv(r) SMCC 90 and
MethocelTM Premium CR cannot control the tramadol release effectively for >12h
and tablets containing DisintequikTM MCC 25 and MethocelTM Premium CR >8h.
PMID- 27496050
TI - Advances of blood cell-based drug delivery systems.
AB - Blood cells, including erythrocytes, leukocytes and platelets are used as drug
carriers in a wide range of applications. They have many unique advantages such
as long life-span in circulation (especially erythrocytes), target release
capacities (especially platelets), and natural adhesive properties (leukocytes
and platelets). These properties make blood cell based delivery systems, as well
as their membrane-derived carriers, far superior to other drug delivery systems.
Despite the advantages, the further development of blood cell-based delivery
systems was hindered by limitations in the source, storage, and mass production.
To overcome these problems, synthetic biomaterials that mimic blood cell and
nanocrystallization of blood cells have been developed and may represent the
future direction for blood cell membrane-based delivery systems. In this paper,
we review recent progress of the rising blood cell-based drug delivery systems,
and also discuss their challenges and future tendency of development.
PMID- 27496051
TI - Gradient adjustment method for better discriminating correlating and non
correlating regions of physiological signals: application to the partitioning of
impaired and intact zones of cerebral autoregulation.
AB - Cerebral blood flow (CBF) is regulated over a range of systemic blood pressures
by the cerebral autoregulation (CA) control mechanism. This range lies within the
lower and upper limits of autoregulation (LLA, ULA), beyond which blood pressure
drives CBF, and CA function is considered impaired. A standard method to
determine autoregulation limits noninvasively using NIRS technology is via the
COx measure: a moving correlation index between mean arterial pressure and
regional oxygen saturation. In the intact region, there should be no correlation
between these variables whereas in the impaired region, the correlation index
should approximate unity. In practice, however, the data may be noisy and/or the
intact region may often exhibit a slightly positive relationship. This positive
relationship may render traditional autoregulation limit calculations difficult
to perform, resulting in the need for manual interpretation of the data using
arbitrary thresholds. Further, the underlying mathematics of the technique are
asymmetric in terms of the results produced for impaired and intact regions and
are, in fact, not computable for the ideal case within the intact region. In this
work, we propose a novel gradient adjustment method (GACOx) to enhance the
differences in COx values observed in the intact and impaired regions. Results
from a porcine model (N = 8) are used to demonstrate that GACOx is successful in
determining LLA values where traditional methods fail. It is shown that the
derived GACOx indices exhibit a mean difference between the intact/impaired
regions of 1.54 +/- 0.26 (mean +/- SD), compared to 0.14 +/- 0.10 for the
traditional COx method. The GACOx effectively polarizes the COx data in order to
better differentiate the intact and impaired zones and, in doing so, makes the
determination of the LLA and ULA points a simpler and more consistent task. The
method lends itself to the automation of the robust determination of
autoregulation zone limits.
PMID- 27496052
TI - Aneuploidy screening of embryonic stem cell clones by metaphase karyotyping and
droplet digital polymerase chain reaction.
AB - BACKGROUND: Karyotypic integrity is essential for the successful germline
transmission of alleles mutated in embryonic stem (ES) cells. Classical methods
for the identification of aneuploidy involve cytological analyses that are both
time consuming and require rare expertise to identify mouse chromosomes. RESULTS:
As part of the International Mouse Phenotyping Consortium, we gathered data from
over 1,500 ES cell clones and found that the germline transmission (GLT)
efficiency of clones is compromised when over 50 % of cells harbour chromosome
number abnormalities. In JM8 cells, chromosomes 1, 8, 11 or Y displayed copy
number variation most frequently, whilst the remainder generally remain
unchanged. We developed protocols employing droplet digital polymerase chain
reaction (ddPCR) to accurately quantify the copy number of these four
chromosomes, allowing efficient triage of ES clones prior to microinjection. We
verified that assessments of aneuploidy, and thus decisions regarding the
suitability of clones for microinjection, were concordant between classical
cytological and ddPCR-based methods. Finally, we improved the method to include
assay multiplexing so that two unstable chromosomes are counted simultaneously
(and independently) in one reaction, to enhance throughput and further reduce the
cost. CONCLUSION: We validated a PCR-based method as an alternative to classical
karyotype analysis. This technique enables laboratories that are non-specialist,
or work with large numbers of clones, to precisely screen ES cells for the most
common aneuploidies prior to microinjection to ensure the highest level of
germline transmission potential. The application of this method allows early
exclusion of aneuploid ES cell clones in the ES cell to mouse conversion process,
thus improving the chances of obtaining germline transmission and reducing the
number of animals used in failed microinjection attempts. This method can be
applied to any other experiments that require accurate analysis of the genome for
copy number variation (CNV).
PMID- 27496053
TI - Tobacco smoking is associated with decreased semen quality.
AB - BACKGROUND: Tobacco smoking is a public health issue and has been implicated in
adverse reproductive outcomes including semen quality. Available data however
provides conflicting findings. The objective of this study was to evaluate the
effect of tobacco smoking on semen quality among men in Ghana. METHODS: In this
study, a total of 140 subjects were recruited, comprising 95 smokers and 45 non
smokers. Smokers were further categorized into mild, moderate and heavy smokers.
Semen parameters such as sperm concentration, motility, viability and normal
morphology were measured according to the World Health Organisation criteria.
RESULTS: The study showed that smokers had significantly lower semen volume,
sperm concentration, sperm motility, total sperm count, sperm morphology, free
testosterone and follicle stimulating hormone (p <0.05 respectively), compared
with non-smokers. Smokers were at a higher risk of developing oligospermia,
asthenozoospermia and teratozoospermia (OR = 3.1, 4.2 and, 4.7; p <0.05) than non
smokers. CONCLUSION: Results demonstrated a decline in semen quality in a dose
dependent tobacco smoking manner.
PMID- 27496054
TI - Curcumin-Mediated Photodynamic Inactivation of Norovirus Surrogates.
AB - Photodynamic inactivation (PDI) is extensively used to inactivate different type
of pathogens through the use of photosensitizers (PS). Curcumin has been
identified as an excellent natural photosensitizer with some potential
applications in the food industry. The aim of this study was to assess the
antiviral activity of photoactivated curcumin on norovirus surrogates, feline
calicivirus (FCV), and murine norovirus (MNV). Initially, different
concentrations of curcumin (13.5-1358 uM) were individually mixed with each virus
at titers of ca. 6-7 log TCID50/ml and photoactivated by LED blue light with
light dose of 3 J/cm2. Results showed that photoactivated curcumin at 50 ug/mL
reduced FCV titers by almost 5 log after incubation at 37 degrees C for 30 min.
Lower antiviral activity (0.73 log TCID50/mL reduction) was reported for MNV. At
room temperature, curcumin at 5 ug/mL reduced FCV titers by 1.75 log TCID50/mL.
These results represent a step forward in improving food safety using
photoactivated curcumin as an alternative natural additive to reduce viral
contamination.
PMID- 27496056
TI - Cooperation of Amphiphilicity and Crystallization for Regulating the Self
Assembly of Poly(ethylene glycol)-block-poly(lactic acid) Copolymers.
AB - Tuning the amphiphilicity of block copolymers has been extensively exploited to
manipulate the morphological transition of aggregates. The introduction of
crystallizable moieties into the amphiphilic copolymers also offers increasing
possibilities for regulating self-assembled structures. In this work, we
demonstrate a detailed investigation of the self-assembly behavior of amphiphilic
poly(ethylene glycol)-block-poly(l-lactic acid) (PEG-b-PLLA) diblock copolymers
with the assistance of a common solvent in aqueous solution. With a given length
of the PEG block, the molecular weight of the PLA block has great effect on the
morphologies of self-assembled nanoaggregates as a result of varying molecular
amphiphilicity and polymer crystallization. Common solvents including N,N
dimethylformamide, dioxane, and tetrahydrofuran involved in the early stage of
self-assembly led to the change in chain configuration, which further influences
the self-assembly of block copolymers. This study expanded the scope of PLA-based
copolymers and proposed a possible mechanism of the sphere-to-lozenge and
platelet-to-cylinder morphological transitions.
PMID- 27496055
TI - A retrospective analysis of Victorian and South Australian clinical registries
for prostate cancer: trends in clinical presentation and management of the
disease.
AB - BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed malignancy
reported to Australian cancer registries with numerous studies from individual
registries summarizing diagnostic and treatment characteristics. The aim of this
study was to describe annual trends in clinical and treatment characteristics,
and changes in surveillance practice within a large combined cohort of men with
PCa in South Australia (SA) and Victoria, Australia in 2008-2013. METHODS: Common
data items from clinical registries in SA and Victoria were merged to develop a
cross-jurisdictional dataset consisting of 13,598 men with PCa. Frequencies were
used to describe these variables using the National Comprehensive Cancer Network
risk of disease progression categories in 10 year age groups. A logistic
regression analysis was performed to assess the impact of a number of factors
(both individually and together) on the likelihood of men receiving no active
treatment within twelve months of the diagnosis (i.e. managed with active
surveillance/watchful waiting). RESULTS: Trend analysis showed that over time:
(1) men in SA and Victoria are being diagnosed at older age in 2013, 66.1 (SD =
9.7) years compared to 2009 (64.5 (SD = 9.7)); (2) diagnostic methods and
characteristics have changed with time; and (3) types of the treatments have
changed, with more men having no active treatment. The majority of men were
diagnosed with Prostate-Specific Antigen (PSA) <10 ng/mL (66 %) and Grade Group <
4 (65 %). Nearly seventy percent received radical treatment within 12 months of
diagnosis, while ~20 % had no active treatment. In 14 % of cases treatment was
not recorded or had not commenced. Having no active treatment was strongly
associated older age, lower PSA and lower Grade Group at diagnosis, and in 2013
it was offered more frequently (more than 3 times) than in 2009 (OR = 2.63, 95 %
CI: 2.16-3.22). CONCLUSIONS: Findings of this study provide the first cross
jurisdictional description of PCa characteristics and management in Australia.
These findings will provide benchmarking for ongoing monitoring and feedback of
disease management and outcomes of PCa through the Prostate Cancer Outcomes
Registry-Australia New Zealand to improve evidence-based practice.
PMID- 27496057
TI - Lost in translation: impact of language barriers on children's healthcare.
AB - PURPOSE OF REVIEW: As the cultural and linguistic diversity of the United States
grows, a greater number of patients with limited English proficiency will enter
the healthcare system. Best practices for the care of these individuals include
identification of their language assistance needs and prompt provision of
interpreter services. This review will summarize the legal basis for providing
language access in the healthcare setting, discuss the impact of interpretation
services on clinical care, and explore the effects of language barriers on health
outcomes. RECENT FINDINGS: There has been greater awareness of language as an
important and independent determinant in the racial and ethnic disparities that
exist in healthcare. Studies have shown that there is suboptimal identification
of patients who require linguistic assistance and, as such, there are missed
opportunities to bridge language gaps with many of our patients. The lack of
interpretation, or use of informal, untrained interpreters, has significant
effects on patient safety, quality of care, and patient satisfaction. SUMMARY:
Though federal and regulatory guidelines mandate meaningful access to language
services, such processes are still a work in progress in many healthcare
settings. Further research and quality improvement initiatives are needed to
provide clinicians the knowledge and skills needed to effectively communicate
with their limited English proficient patients.
PMID- 27496058
TI - The development of moral sense and moral thinking.
AB - PURPOSE OF REVIEW: The review critically evaluates recent claims that infants
have innate knowledge of morality and examines the sources of moral norms. RECENT
FINDINGS: Many studies show that toddlers readily help adults with daily tasks. A
more contentious set of studies suggests that young infants prefer actors who
help others to those who hinder them. Some researchers have interpreted these
findings as indicating that morality is innately present in humans. Others look
to alternative explanations in developmental systems theory. SUMMARY: Explaining
the emergence of morality as innate, or wholly socialized, is problematic;
instead morality could emerge in a developmental system in which children's early
capacities are shaped by interpersonal engagement. Children's improving ability
to coordinate with others at a practical level is later transformed through
language and reflective thought, as children gain the ability to talk about what
was previously implicit in interaction. Throughout, parents and caregivers have
many opportunities to foster children's moral development in daily interactions.
PMID- 27496059
TI - Reading disorders and dyslexia.
AB - PURPOSE OF REVIEW: We review current knowledge about the nature of reading
development and disorders, distinguishing between the processes involved in
learning to decode print, and the processes involved in reading comprehension.
RECENT FINDINGS: Children with decoding difficulties/dyslexia experience deficits
in phoneme awareness, letter-sound knowledge and rapid automatized naming in the
preschool years and beyond. These phonological/language difficulties appear to be
proximal causes of the problems in learning to decode print in dyslexia. We
review data from a prospective study of children at high risk of dyslexia to show
that being at family risk of dyslexia is a primary risk factor for poor reading
and children with persistent language difficulties at school entry are more
likely to develop reading problems. Early oral language difficulties are strong
predictors of later difficulties in reading comprehension. SUMMARY: There are two
distinct forms of reading disorder in children: dyslexia (a difficulty in
learning to translate print into speech) and reading comprehension impairment.
Both forms of reading problem appear to be predominantly caused by deficits in
underlying oral language skills. Implications for screening and for the delivery
of robust interventions for language and reading are discussed.
PMID- 27496060
TI - The effects of hybridization on divergent venom phenotypes: Characterization of
venom from Crotalus scutulatus scutulatus * Crotalus oreganus helleri hybrids.
AB - Hybridization between divergent species can be analyzed to elucidate expression
patterns of distinct parental characteristics, as well as to provide information
about the extent of reproductive isolation between species. A known hybrid cross
between two rattlesnakes with highly divergent venom phenotypes provided the
opportunity to examine occurrence of parental venom characteristics in the F1
hybrids as well as ontogenetic shifts in the expression of these characters as
the hybrids aged. Although venom phenotypes of adult rattlesnake venoms are known
for many species, the effect of hybridization on phenotype inheritance is not
well understood, and effects of hybridization on venom ontogeny have not yet been
investigated. The current study investigates both phenomena resulting from the
hybridization of a male snake with type I degradative venom, Crotalus oreganus
helleri (Southern Pacific Rattlesnake), and a female snake with type II highly
toxic venom, Crotalus scutulatus scutulatus (Mojave Rattlesnake). SDS-PAGE,
enzymology, Western blot and reversed phase HPLC (RP-HPLC) were used to
characterize the venom of the C. o. helleri male, the C. s. scutulatus female and
their two hybrid offspring as they aged. In general, Crotalus o. helleri * C. s.
scutulatus hybrid venoms appeared to exhibit overlapping parental venom profiles,
and several different enzyme activity patterns. Both hybrids expressed C. o.
helleri father-specific myotoxins as well as C. s. scutulatus mother-specific
Mojave toxin. Snake venom metalloprotease activity displayed apparent sex
influenced expression patterns, while hybrid serine protease activities were
intermediate to parental activities. The C. s. scutulatus * C. o. helleri hybrid
male's venom profile provided the strongest evidence that type I and type II
venom characteristics are expressed simultaneously in hybrid venoms, as this
snake contained distinctive characteristics of both parental species. However,
the possibility of sex-influenced development of metalloprotease activity, as
seen in the ontogenetic shifts of the hybrid female, may influence the levels of
expression of both type I and type II characteristics in hybrid venoms.
Ultimately, the chronological analysis of this known hybrid system reveals the
most distinct characteristics that can be used in determining successful
hybridization between snakes that follow the type I-type II trend in rattlesnake
venom composition, namely the presence of metalloprotease activity and Mojave
toxin.
PMID- 27496061
TI - Description of Loxtox protein family and identification of a new group of
Phospholipases D from Loxosceles similis venom gland.
AB - Envenoming resulting from Loxosceles spider bites (loxoscelism) is a recognized
public health problem in Brazil. However, the pathophysiology of loxoscelism
caused by L. similis bites, which is widespread in Brazil, remains poorly
understood. In the present work, the RNA sequencing (RNA-Seq - Next Generation
sequencing - NGS) of the L. similis venom gland was performed to identify and
analyze the sequences of the key component phospholipase D. The sequences were
aligned based on their classical domains, and a phylogenetic tree was
constructed. In the bioinformatics analysis, 23 complete sequences of
phospholipase D proteins were found and classified as Loxtox proteins, as they
contained the characteristic domains of phospholipase D: the active site, the
Mg(2+)-binding domain, and the catalytic loop. Three phospholipase D sequences
with non-canonical domains were also found in this work. They were analyzed
separately and named PLDs from L. similis (PLD-Ls). This study is the first to
characterize phospholipase D sequences from Loxosceles spiders by RNA-Seq. These
results contribute new knowledge about the composition of L. similis venom,
revealing novel tools that could be used for pharmacological, immunological, and
biotechnological applications.
PMID- 27496062
TI - Effective management of cricopharyngeal achalasia in infants and children with
dilatation alone.
AB - AIM: Cricopharyngeal achalasia (CPA) is a rare clinical condition that is
characterized by aspiration, choking, and nasopharyngeal regurgitation. The aim
of this study is to introduce the outcomes of dilatation alone in children with
CPA. PATIENTS AND METHOD: After the evaluation of upper esophageal sphincter with
endoscopy, dilatation was performed. All patients underwent videofluoroscopic
evaluation and swallowing therapy after the surgical procedure. A retrospective
chart review was performed in children with CPA. RESULTS: Thirty children who
were videofluoroscopically proven to have CPA were included in the study. Their
age range was 15days-7years (median 11months). Twenty-one of them were
neurologically impaired. Two children were lost to follow-up. Nineteen patients
(68%) had a total resolution of CPA and were symptom-free with 1-6 dilatations
(median 2). Three of the children (11%) who were severely neurologically impaired
had resistant CPA. Three children (11%) treated recently with short follow-up
were added to the group. Their VFS evaluations demonstrated improvement, thus we
accepted their result as successful. There were two perforations in the series.
Three patients died; one 2-month-old (2500g) baby who was accepted from the
intensive care unit passed away on postoperative on the 7th day. Two other babies
who were unresponsive to dilatation therapy died on follow-up. CONCLUSION:
Dilatation can be a safe and effective method on children who are correctly
diagnosed to have CPA.
PMID- 27496063
TI - Economic and operational burden associated with malnutrition in chronic
obstructive pulmonary disease.
AB - BACKGROUND: Malnutrition is common in patients with chronic obstructive pulmonary
disease (COPD). This study aimed to explore its association with all-cause
mortality, emergency hospitalisation and subsequently healthcare costs. METHODS:
A prospective cohort observational pilot study was carried out in outpatients
with COPD that attended routine respiratory clinics at a large tertiary
Australian hospital during 2011. Electronic hospital records and hospital coding
was used to determine nutritional status and whether a patient was coded as
nourished or malnourished and information on healthcare use and 1-year mortality
was recorded. RESULTS: Eight hundred and thirty four patients with COPD attended
clinics during 2011, of those 286 went on to be hospitalised during the 12 month
follow-up period. Malnourished patients had a significantly higher 1-year
mortality (27.7% vs. 12.1%; p = 0.001) and were hospitalised more frequently
(1.11 SD 1.24 vs. 1.51 SD 1.43; p = 0.051). Only malnutrition (OR 0.36 95% CI
0.14-0.91; p = 0.032) and emergency hospitalisation rate (OR 1.58 95% CI 1.2-2.1;
p = 0.001) were independently associated with 1-year mortality. Length of
hospital stay was almost twice the duration in those coded for malnutrition
(11.57 SD 10.93 days vs. 6.67 SD 10.2 days; p = 0.003) and at almost double the
cost (AUD $23,652 SD $26,472 vs. $12,362 SD $21,865; p = 0.002) than those who
were well-nourished. CONCLUSION: Malnutrition is an independent predictor of 1
year mortality and healthcare use in patients with COPD. Malnourished patients
with COPD present both an economic and operational burden.
PMID- 27496064
TI - Performance assessment of a portable mass spectrometer using a linear ion trap
operated in non-scanning mode.
AB - RATIONALE: The desire for mass spectrometer portability provides the motivation
for simpler, lighter electronics to deliver switched potentials applied to the
electrodes of the linear ion trap operated in non-scanning mode. Using a novel
method of modelling and theoretical analysis, we simulate the mass analyser
performance under these unfavourable operating conditions. METHODS: The
electrical fields are simulated using the Charge Particle Optics software which
employs the boundary element method. The ion trajectories are computed from the
ion cage of the EI source to the interior of the trap where the ions are
confined. The spatial/temporal ion distributions during injection are calculated
from the individual ion trajectories computed with constant time-steps. Due to
geometric non-linearities, betay = 0 lines close to the apex of the stability
diagram have been computed for different initial positions with zero initial
velocities in order to define the acceptable maximum axial extension. RESULTS:
The DC potential well depth has been estimated at about 15 eV from the axial
velocity distribution, and the minimum time of ion injection at 120 MUs from the
temporal ion distribution. To ensure a mass separation of one unit and the
confinement of the whole of the injected ions, buffer gas cooling is necessary to
reduce the trajectory excursion amplitudes to 0.1 and 15 mm in the radial and
axial directions, respectively. CONCLUSIONS: The portable mass spectrometer is
predicted to achieve a mass resolution of better than one mass unit providing
that helium buffer gas is used. An additional cooling sequence has to be added
prior to moving the operating point toward the apex. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27496065
TI - Increasing the availability of l-arginine and nitric oxide increases sensitivity
of nitrous oxide (N2O)-insensitive inbred mice to N2O-induced antinociception.
AB - Nitrous oxide (N2O)-induced antinociception in mice is dependent on the
neuromodulator nitric oxide (NO). In contrast to C57BL/6J (B6) mice, DBA/2J (D2)
mice fail to respond to N2O with a robust antinociceptive response or with an
increase in brain nitric oxide synthase (NOS) enzyme activity, suggesting that
failure of D2 mice to respond to N2O might result from a deficit of NO function.
Therefore, it was of interest to determine whether increasing the availability of
NO might increase sensitivity of D2 mice to N2O. Male D2 mice were pretreated
with sub-antinociceptive intracerebroventricular doses of the NO donor 3
morpholinosydnoimine or the NO precursor l-arginine then assessed for
responsiveness to N2O-induced antinociception using the acetic acid abdominal
constriction test. Both pretreatments increased the antinociceptive
responsiveness of D2 mice to N2O. These results indicate that the NOS enzyme in
D2 mice is functional and that the deficit in NO function that obstructs
sensitivity to N2O-induced antinociception may lie in availability or utilization
of l-arginine.
PMID- 27496066
TI - Large animal canine endovascular ischemic stroke models: A review.
AB - BACKGROUND: Stroke is one of the leading causes of death and long-term disability
worldwide. Recent exciting developments in the field with endovascular treatments
have shown excellent outcomes in acute ischemic stroke. Prior to translating
these treatments to human populations, a large-animal ischemic stroke model is
needed. With the advent of new technologies in digital subtraction angiography,
less invasive endovascular stroke models have been developed. Canines have
gyrencephalic brain similar to human brain and accessible neurovascular anatomy
for stroke model creation. Canine stroke model can be widely utilized to
understand the disease process of stroke and to develop novel treatment. Less
invasive endovascular internal carotid emboli injection and coil embolization
methods can be used to simulate transient or permanent middle cerebral artery
occlusion. Major restriction includes the extensive collateral circulation of
canine cerebral arteries that can limit the stroke size. Transient internal
carotid artery occlusion can decrease collateral circulation and increase stroke
size to some degree. Additional method of manipulating the extent of collateral
circulation needs to be studied. Other types of canine stroke models, including
vertebral artery occlusion and basilar artery occlusion, can also be accomplished
by endovascular thrombi injection. CONCLUSIONS: We extensively review the
literature on endovascular technique of creating canine ischemic stroke models
and their application in finding new therapies for ischemic stroke.
PMID- 27496067
TI - Safety, adherence and efficacy of exercise training in solid-organ transplant
candidates: A systematic review.
AB - BACKGROUND: Patients awaiting solid-organ transplantation may be encouraged to
undertake exercise training to improve pre- and post-transplant outcomes.
However, the safety, adherence and efficacy of exercise training in this
population remain unclear. METHODS: All randomized, non-randomized and non
controlled trials of exercise training interventions in solid-organ transplant
candidates were included. The Cochrane risk of bias tool and a modified Newcastle
Ottawa scale were used to assess procedural quality. Safety was defined as the
number of reported adverse events during exercise training. Adherence was
evaluated from session attendance, and efficacy as changes in cardiorespiratory
fitness (CRF), exercise capacity, muscular strength, health-related quality of
life (HR-QoL) and lung function. RESULTS: Eleven studies involving 874 patients
were included: four randomized controlled, one non-randomized controlled and six
non-controlled trials. Six studies included heart transplant candidates and five
involved patients awaiting lung transplantation. Three trials included aerobic
only training, one incorporated resistance-only exercise and seven combined
modalities. Twelve adverse events were reported with four due to exercise,
although methods to collect these data were often omitted. Exercise adherence
ranged from 82.5% to 100%, but was poorly described. No significant between-group
changes attributable to exercise training were demonstrated. However, significant
within-group improvements in CRF, exercise capacity, muscular strength, lung
function and HR-QoL were observed. CONCLUSIONS: Patients awaiting heart or lung
transplant appear to tolerate exercise training despite the larger number of
adverse events compared to other high-risk populations. Exercise training
demonstrated within-group benefits for several outcomes, with no significant
between-group differences. Randomized controlled trials with sufficient
statistical power are required for all solid-organ transplant candidates.
PMID- 27496068
TI - Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals
for the targeted treatment of bone metastases.
AB - Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha
and conversion electron emitting radioisotopes have been investigated for the
targeted treatment of painful bone metastases for >35years. We performed a
systematic literature search and focused on the pharmaceutical development,
preclinical research and early human studies of these radiopharmaceuticals. The
characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are
presented and compliance with these criteria by the compounds discussed is
verified. The importance of both composition and preparation conditions for the
stability and biodistribution of several agents is discussed. Very few studies
have described the characterization of these products, although knowledge on the
molecular structure is important with respect to in vivo behavior. This review
discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of
which only six agents have progressed to clinical use. Extensive clinical studies
have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of
these, (153)Sm-EDTMP represents the only compound with worldwide marketing
authorization. (177)Lu-EDTMP has recently received approval for clinical use in
India. This review illustrates that a thorough understanding of the
radiochemistry of these agents is required to design simple and robust
preparation and quality control methods, which are needed to fully exploit the
potential benefits of these theranostic radiopharmaceuticals. Extensive
biodistribution and dosimetry studies are indispensable to provide the portfolios
that are required for assessment before human administration is possible. Use of
the existing knowledge collected in this review should guide future research
efforts and may lead to the approval of new promising agents.
PMID- 27496069
TI - Comment on: Inflammatory mediators in osteoarthritis: A critical review of the
state-of-the art, prospects, and future challenges.
PMID- 27496070
TI - Optical coherence tomography angiography in treated type 2 neovascularization
undergoing monthly anti-VEGF treatment.
PMID- 27496071
TI - Design and synthesis of new 2-anilinoquinolines bearing N-methylpicolinamide
moiety as potential antiproliferative agents.
AB - A series of new 2-anilinoquinolines 6a-o possessing the substantial N
methylpicolinamide motif at C5 has been designed and synthesized as sorafenib
analogs. The antiproliferative activities of the target compounds were
preliminarily appraised against a panel of three human cancer cell lines (MCF-7,
SK-BR3, and HCT116), and a selected array was further tested over a panel of
approximately 60 cancer cell lines at NCI at 10 MUM concentration. Interestingly,
compounds 6c, 6d, 6j, 6k, and 6l showed promising selective anticancer activities
(growth inhibition >80%) toward certain cancer cells at 10 MUM testing dose.
Compounds 6d and 6j were advanced to five-dose testing mode to determine their
GI50 values and compared with our previously reported ureidoquinoline B and
sorafenib as reference compounds. The 4-chloro-3-trifluoromethylaniline
derivative 6j manifested superior potency than both compound B and sorafenib over
eleven and eight cell lines, respectively. It showed GI50 values of 0.36, 0.66,
0.68, and 0.60 MUM against the breast MDA-MB-468, renal A498, and melanoma SK-MEL
5 and UACC-62 cell lines, respectively. Moreover, both 6d and 6j exerted low
cytotoxic effects against HFF-1 normal cell line. Furthermore, compounds 6d and
6j were tested against both B-RafV600E and C-Raf kinases and displayed modest
inhibitory activities, which were justified by molecular docking study. Compound
6j could serve as a promising candidate for further development of potent
anticancer chemotherapeutics.
PMID- 27496072
TI - Is Assisted Dying the Baby Boomers' Last Frontier?
PMID- 27496073
TI - A profile of Emanuel A. Friedman, MD, DMedSci.
PMID- 27496074
TI - Risk Factors for Priapism Readmission.
AB - INTRODUCTION: Priapism is a urologic emergency with a tendency to recur in some
patients. The frequency of, time to, and risk factors for priapism recurrence
have not been well characterized. AIM: To identify predictors of priapism
readmission. METHODS: We used the New York Statewide Planning and Research
Cooperative System database to identify patients presenting to emergency
departments with priapism from 2005 through 2014. Patients were tracked up to 12
months after initial presentation. Proportional hazards regression was used to
identify risk factors for priapism readmission. MAIN OUTCOME MEASURES:
Readmissions for priapism. RESULTS: The analytic cohort included 3,372 men with a
diagnosis of priapism. The average age at first presentation was 39 +/- 18 years
and 40% were black. Within 1 year, 24% of patients were readmitted for recurrent
priapism, 68% of whom were readmitted within 60 days. On multivariate analysis,
sickle cell disease (hazard ratio [HR] = 2.5, 95% CI = 2.0-3.0), drug abuse or
psychiatric disease (HR = 1.9, 95% CI = 1.6-2.2), erectile dysfunction history
(HR = 1.9, 95% CI = 1.5-2.3), other than commercial medical insurance (HR = 1.2,
95% CI = 1.0-1.4), and inpatient admission for initial priapism event (HR = 0.5,
95% CI = 0.4-0.6) were significant risk factors for readmission. CONCLUSION:
Nearly one fourth of patients with priapism were readmitted for recurrent
priapism within 1 year of initial presentation. Most readmissions were within 60
days. Future research should focus on strategies to decrease recurrences in high
risk patients.
PMID- 27496075
TI - Improvement of the soil nitrogen content and maize growth by earthworms and
arbuscular mycorrhizal fungi in soils polluted by oxytetracycline.
AB - Interactions between earthworms (Eisenia fetida) and arbuscular mycorrhizal fungi
(Rhizophagus intraradices, AM fungi) have been suggested to improve the maize
nitrogen (N) content and biomass and were studied in soils polluted by
oxytetracycline (OTC). Maize was planted and amended with AMF and/or earthworms
(E) in the soil with low (1mgkg(-1) soil DM) or high (100mgkg(-1) soil DM)
amounts of OTC pollution in comparison to soil without OTC. The root
colonization, shoot and root biomass, shoot and root N contents, soil nitrogen
forms, ammonia-oxidizing bacteria (AOB) and archaea (AOA) were measured at
harvest. The results indicated that OTC decreased maize shoot and root biomass
(p<0.05) by mediating the soil urease activity and AOB and AOA abundance, which
resulted in a lower N availability for maize roots and shoots. There was a
significant interaction between earthworms and AM fungi on the urease activity in
soil polluted by OTC (p<0.05). Adding earthworms or AM fungi could increase the
maize biomass and N content (p<0.05) in OTC polluted soil by increasing the
urease activity and relieving the stress from OTC on the soil N cycle. AM fungi
and earthworms interactively increased maize shoot and root biomass (p<0.05) in
the OTC polluted soils through their regulation of the urease activity and the
abundance of ammonia oxidizers, resulting in different soil NH4(+)-N and NO3(-)-N
contents, which may contribute to the N content of maize shoots and roots.
Earthworms and AM fungi could be used as an efficient method to relieve the OTC
stress in agro-ecosystems.
PMID- 27496076
TI - Major geogenic factors controlling geographical clustering of urolithiasis in
China.
AB - The prevalence of urolithiasis is increasing across the world and exhibits a
distinctive characteristic of geographical distribution. Geographical clustering
and major geogenic factors for urolithiasis prevalence in China were
investigated. High risks of urolithiasis are found in southern China clustered in
coastal provinces such as Fujian and Zhejiang and karst regions such as Sichuan,
Chongqing, Guizhou, Guangxi, Guangdong, Hunan, and Hubei. The predominant urinary
stone composition is a mixture of calcium oxalate and phosphate. We found that
the spatial distribution of phosphate-type stones is closely related to that of
phosphate ore deposits and carbonate rocks. Hot or warm climate and seasons
increase the risk of lithogenesis through high average air temperature. Water and
soil environment influence the quality and composition of drinking water and
food, thus affecting stone formation in the urinary system. In particular, the
increase of Ca(2+)/Mg(2+) ratio (in meq) in drinking water might be the main
factor. Besides, the high content of calcium in local plants grown on karst soils
and the intake of high oxalate food might contribute to the high prevalence in
South China. This study indicates that urolithiasis could be endemic, with
geogenic factors playing critical roles in urolithiasis etiology.
PMID- 27496077
TI - Fate of mixed pesticides in an integrated recirculating constructed wetland
(IRCW).
AB - In this study, three model integrated recirculating constructed wetlands (IRCWs)
planted with and without Cyperus alternifolius were used to investigate their
ability to remove four pesticides (chlorpyrifos, endosulfan, fenvalerate,
diuron). Iron (Fe)-impregnated biochar produced by Cyperus alternifolius was
added as a primary substrate. Results showed that all four pesticides were
efficiently removed in the three IRCWs. The highest pesticide removals were
achieved when Fe-impregnated biochar was added to the IRCW (99%), followed by the
planted (64-99%) and plant-free IRCW (45-99%). The removal of pesticides in IRCWs
followed first-order kinetics, with half-lives of 1.5-11.6h. A mass balance study
revealed that sorption (32.2-98.6%) and microbial degradation (1.3-52.8%) were
the main removal processes in all IRCWs. This study suggests that the IRCW is a
promising system to treat pesticide-contaminated water, and plant and Fe
impregnated biochar can enhance pesticide removal.
PMID- 27496079
TI - Fulminant Epstein-Barr virus-associated hemophagocytic syndrome in a renal
transplant patient and review of the literature.
AB - We describe a rare fulminant case of Epstein-Barr virus-associated hemophagocytic
syndrome (HPS) in a 37-year-old female renal transplant patient,
indistinguishable from severe sepsis clinically and in the laboratory. HPS
involves rapidly escalating immune system activation, resulting in a cytokine
cascade, which can, especially in immunocompromised patients, lead to multi-organ
failure, and even death. Thirty-two Herpesviridae-associated HPS cases in renal
transplant patients have been reported and are reviewed. Overall mortality is 47%
(15/32 cases).
PMID- 27496078
TI - Sexual Function in 16- to 21-Year-Olds in Britain.
AB - PURPOSE: Concern about young people's sexuality is focused on the need to prevent
harmful outcomes such as sexually transmitted infections and unplanned pregnancy.
Although the benefit of a broader perspective is recognized, data on other
aspects of sexuality, particularly sexual function, are scant. We sought to
address this gap by measuring the population prevalence of sexual function
problems, help seeking, and avoidance of sex in young people. METHODS: A cross
sectional stratified probability sample survey (Natsal-3) of 15,162 women and men
in Britain (response rate: 57.7%), using computer-assisted self-interviews. Data
come from 1875 (71.9%) sexually active, and 517 sexually inactive (18.7%),
participants aged 16-21 years. Measures were single items from a validated
measure of sexual function (the Natsal-SF). RESULTS: Among sexually active 16- to
21-year-old participants, 9.1% of men and 13.4% of women reported a distressing
sexual problem lasting 3 months or more in the last year. Most common among men
was reaching a climax too quickly (4.5%), and among women was difficulty in
reaching climax (6.3%). Just over a third (35.5%) of men and 42.3% of women
reporting a problem had sought help, but rarely from professional sources. Among
those who had not had sex in the last year, just >10% of young men and women said
they had avoided sex because of sexual difficulties. CONCLUSIONS: Distressing
sexual function problems are reported by a sizeable minority of sexually active
young people. Education is required, and counseling should be available, to
prevent lack of knowledge, anxiety, and shame progressing into lifelong sexual
difficulties.
PMID- 27496080
TI - The prognostic value of serum signal peptide-Cub-Egf domain-containing protein-1
concentrations in acute intracerebral hemorrhage.
AB - BACKGROUND: Signal peptide-Cub-Epidermal growth factor domain-containing protein
1 (SCUBE1) in peripheral blood, which is identified as a marker for coagulation,
was reported to be an independent predictor of poor outcome in some illnesses. We
investigated the clinical utility of serum SCUBE1 in the prognosis of
intracerebral hemorrhage (ICH). METHODS: A total of 128 consecutive patients,
admitted to emergency service due to acute ICH, and 128 healthy individuals were
included in this prospective study. The patients were followed up until 6months
or death. An unfavorable outcome was defined as modified Rankin Scale score>2.
RESULTS: Serum SCUBE1 concentration was markedly higher in patients than in
controls and was associated with hematoma volume, National Institutes of Health
Stroke Scale (NIHSS) score and blood platelet count. After adjustment for
hematoma volume and NIHSS score, it was still related to early neurological
deterioration, hematoma growth, 1-week mortality, 6-month mortality, 6-month
unfavorable outcome and 6-month overall survival. Additionally, serum SCUBE1
significantly improved areas under receiver operating characteristic curve of
hematoma volume and NIHSS score to predict 6-month unfavorable outcome.
CONCLUSIONS: Increased serum SCUBE1 concentrations have close relation to
increasing severity and poor prognosis of ICH.
PMID- 27496081
TI - Reduced levels of potential circulating biomarkers of cardiovascular diseases in
apparently healthy vegetarian men.
AB - BACKGROUND: Several evidences report that a vegetarian diet is protector against
cardiovascular diseases. Few studies have demonstrated the circulating profile of
cardiovascular biomarkers in vegetarians. Therefore, the aims of the current
study were compared the plasma concentrations of myeloperoxidase (MPO),
metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of MMP (TIMP)-1 and TIMP-2
between healthy vegetarian (Veg) and healthy omnivorous (Omn). METHODS: Using
ELISA and multiplexed bead immunoassay, we measured in plasma from 43 Veg and 41
Omn the cardiovascular biomarkers concentrations cited above. RESULTS: We found
significant lower concentrations of MPO, MMP-9, MMP-2 and MMP-9/TIMP-1 ratio in
Veg compared to Omn (all P<0.05). Moreover, MMP-9 concentrations were correlated
positively with leukocytes and neutrophils count in both groups (all P<0.05).
CONCLUSION: A vegetarian diet is associated with a healthier profile of
cardiovascular biomarkers compared to omnivorous.
PMID- 27496082
TI - Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased
Donors Are Associated With Long-Term Renal Function.
AB - Kidney transplants from living donors (LDs) have a better outcome than those from
deceased donors (DDs). Different factors have been suggested to justify the
different outcome. In this study, we analyzed the infiltration and phenotype of
monocytes/macrophages and the expression of inflammatory and fibrotic markers in
renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline
and 4 months after transplantation. We evaluated their association with medium-
and long-term renal function. At baseline, inflammatory gene expression was
higher in DDs than in LDs. These results were confirmed by the high number of
CD68-positive cells in DD kidneys, which correlated negatively with long-term
renal function. Expression of the fibrotic markers vimentin, fibronectin, and
alpha-smooth muscle actin was more elevated in biopsy specimens from DDs at 4
months than in those from LDs. Gene expression of inflammatory and fibrotic
markers at 4 months and difference between 4 months and baseline correlated
negatively with medium- and long-term renal function in DDs. Multivariate
analysis point to transforming growth factor-beta1 as the best predictor of long
term renal function in DDs. We conclude that early macrophage infiltration,
sustained inflammation, and transforming growth factor-beta1 expression, at least
for the first 4 months, contribute significantly to the difference in DD and LD
transplant outcome.
PMID- 27496083
TI - Disparities in Unmet Service Needs Among Adults with Intellectual and Other
Developmental Disabilities.
AB - BACKGROUND: Due to long waiting lists for services, many adults with intellectual
and developmental disabilities in the United States have unmet service needs.
Little research, however, has identified the characteristics of caregivers and
individuals with intellectual and developmental disabilities that relate to the
unmet service needs among individuals who are waiting for services. METHOD: The
present authors conducted a statewide mail survey of 234 caregivers of
individuals with intellectual and developmental disabilities who were waiting for
services. The present authors identified which parent and individual with
intellectual and developmental disability characteristics were significantly
associated with the number of unmet service needs. RESULTS: Individuals with
intellectual and developmental disabilities who were in poor health, from
minority backgrounds and non-verbal were significantly more likely to have a
greater number of unmet service needs. Additionally, individuals with younger
caregivers and individuals with caregivers from low-income backgrounds were
significantly more likely to report a greater number of unmet service needs.
DISCUSSION: Implications for research and policy are discussed.
PMID- 27496084
TI - Risks of first and subsequent cancers among TP53 mutation carriers in the
National Cancer Institute Li-Fraumeni syndrome cohort.
AB - BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer
predisposition syndrome characterized by a very high lifetime cancer risk and an
early age at diagnosis of a wide cancer spectrum. Precise estimates for the risk
of first and subsequent cancers are lacking. METHODS: The National Cancer
Institute's Li-Fraumeni Syndrome Study includes families meeting the diagnostic
criteria for LFS or Li-Fraumeni-like syndrome, and individuals with a germline
TP53 mutation, choroid plexus carcinoma, adrenocortical carcinoma, or >=3
cancers. Herein, we estimated the cumulative risk and annual hazards for first
and second cancers among TP53 mutation carriers (TP53 positive [TP53+]) using
MATLAB statistical software. RESULTS: This study evaluated 286 TP53+ individuals
from 107 families. The cumulative cancer incidence was 50% by age 31 years among
TP53+ females and 46 years among males, and nearly 100% by age 70 years for both
sexes. Cancer risk was highest after age 20 years for females, mostly due to
breast cancer, whereas among males the risk was higher in childhood and later
adulthood. Among females, the cumulative incidence rates by age 70 years for
breast cancer, soft tissue sarcoma, brain cancer, and osteosarcoma were 54%, 15%,
6%, and 5%, respectively. Among males, the incidence rates were 22%, 19%, and
11%, respectively, for soft tissue sarcoma, brain cancer, and osteosarcoma.
Approximately 49% of those with 1 cancer developed at least another cancer after
a median of 10 years. The average age-specific risk of developing a second cancer
was comparable to that of developing a first cancer. CONCLUSIONS: The cumulative
cancer risk in TP53 + individuals was very high and varied by sex, age, and
cancer type. Additional work, including prospective risk estimates, is needed to
better inform personalized risk management. Cancer 2016;122:3673-81. (c) 2016
American Cancer Society.
PMID- 27496086
TI - "The only sure foundations of medicine are, an intimate knowledge of the human
body, and observation on the effects of medicinal substances on that".
PMID- 27496085
TI - Mechanisms of DHA transport to the brain and potential therapy to
neurodegenerative diseases.
AB - Docosahexaenoic acid (DHA; 22:6 omega-3) is highly enriched in the brain and is
required for proper brain development and function. Its deficiency has been shown
to be linked with the emergence of neurological diseases. Dietary omega-3 fatty
acid supplements including DHA have been suggested to improve neuronal
development and enhance cognitive functions. However, mechanisms of DHA
incorporation in the brain remain to be fully understood. Findings suggested that
DHA is better incorporated when esterified within lysophospholipid rather than
under its non-esterified form. Furthermore, DHA has the potential to be converted
into diverse oxylipins with potential neuroprotective effects. Since DHA is
poorly synthesized de novo, targeting the brain with specific carriers of DHA
might provide novel therapeutic approaches to neurodegenerative diseases.
PMID- 27496088
TI - Prevalence and factors associated with cracked nipples in the first month
postpartum.
AB - BACKGROUND: To assess the prevalence and factors associated with the occurrence
of cracked nipples in the first month postpartum. METHODS: This was a cross
sectional study nested in a cohort of mothers living in Feira de Santana, state
of Bahia, northeastern Brazil. Data from 1,243 mother-child dyads assessed both
at the maternity ward and 30 days after delivery were analyzed. The association
between cracked nipples as reported by mothers and their possible determinants
was analyzed using Poisson regression in a model where the variables were
hierarchically organized into four levels: distal (individual characteristics),
distal intermediate (prenatal characteristics), proximal intermediate (delivery
characteristics), and proximal (postnatal characteristics). RESULTS: The
prevalence of cracked nipples was 32 % (95 % confidence interval [95 % CI] 29.4
34.7) in the first 30 days postpartum. The following factors showed significant
association with the outcome: poor breastfeeding technique (prevalence ratio [PR]
= 3.18, 95 % CI 2.72-3.72); breast engorgement (PR = 1.70, 95 % CI 1.46-1.99);
birth in a maternity ward not accredited by the Baby-Friendly Hospital Initiative
(PR = 1.51, 95 % CI 1.15-1.99); cesarean section (PR = 1.33, 95 % CI 1.13-1.57);
use of a feeding bottle (PR = 1.29, 95 % CI 1.06-1.55); and higher maternal
education level (PR = 1.23, 95 % CI 1.04-1.47). CONCLUSIONS: The prevalence of
cracked nipples was high in our sample. Most of the factors associated with
cracked nipples were related to postnatal characteristics, especially poor
breastfeeding technique, which could be improved to help prevent the condition.
PMID- 27496087
TI - Gene family expansions and contractions are associated with host range in plant
pathogens of the genus Colletotrichum.
AB - BACKGROUND: Many species belonging to the genus Colletotrichum cause anthracnose
disease on a wide range of plant species. In addition to their economic impact,
the genus Colletotrichum is a useful model for the study of the evolution of host
specificity, speciation and reproductive behaviors. Genome projects of
Colletotrichum species have already opened a new era for studying the evolution
of pathogenesis in fungi. RESULTS: We sequenced and annotated the genomes of four
strains in the Colletotrichum acutatum species complex (CAsc), a clade of broad
host range pathogens within the genus. The four CAsc proteomes and secretomes
along with those representing an additional 13 species (six Colletotrichum spp.
and seven other Sordariomycetes) were classified into protein families using a
variety of tools. Hierarchical clustering of gene family and functional domain
assignments, and phylogenetic analyses revealed lineage specific losses of
carbohydrate-active enzymes (CAZymes) and proteases encoding genes in
Colletotrichum species that have narrow host range as well as duplications of
these families in the CAsc. We also found a lineage specific expansion of
necrosis and ethylene-inducing peptide 1 (Nep1)-like protein (NLPs) families
within the CAsc. CONCLUSIONS: This study illustrates the plasticity of
Colletotrichum genomes, and shows that major changes in host range are associated
with relatively recent changes in gene content.
PMID- 27496090
TI - Leukocyte adhesion molecule dynamics after Natalizumab withdrawal in Multiple
Sclerosis.
AB - Cell-adhesion molecules (CAMs) dynamics in Multiple Sclerosis (MS) patients have
been widely studied after Natalizumab (NTZ) introduction. However, their temporal
dynamics after NTZ withdrawal (NTZ-W) has not been described. We prospectively
evaluate changes in the expression levels of CAMs (CD49d, CD29, L-Selectin and
CD11a) involved in T cell migration of 22 MS patients after NTZ-W. CD49d, CD29
and CD11a expression experienced a continuous increase expression two months
after NTZ-W and Cd49d expression at month six after NTZ-W correlated to NTZ
treatment duration, both in CD45+CD4+ and CD45+CD8+. CD49d expression up to month
three after NTZ-W was related to MS activity in CD45+CD8+ at the end of the
study. Results from this study suggest that patients with a longer NTZ treatment
are more susceptible to present a "molecular rebound" after NTZ-W. CD49d
determination may be a useful tool to closely monitor MS activity in patients who
interrupt NTZ.
PMID- 27496089
TI - Oral citrulline supplementation protects female mice from the development of non
alcoholic fatty liver disease (NAFLD).
AB - PURPOSE: Impairments of intestinal barrier function are discussed as risk factors
for the development and progression of non-alcoholic fatty liver disease (NAFLD).
Studies suggest an association between arginine/citrulline homeostasis and the
development of liver damages. Here, the effect of an oral L-citrulline (Cit)
supplement on the development of a Western-style diet (WSD)-induced NAFLD was
determined in mice. METHODS: Female 6- to 8-week-old C57BL/6J mice were either
pair-fed a liquid Western-style or control diet (C) +/- 2.5 g/kg bodyweight Cit
for 6 weeks (C + Cit or WSD + Cit). Indices of liver damage, glucose metabolism,
intestinal barrier function and NO synthesis were measured. RESULTS: While
bodyweight gain was similar between groups, markers of glucose metabolism like
fasting blood glucose and HOMA index and markers of liver damage like hepatic
triglyceride levels, number of neutrophils and plasminogen activator inhibitor-1
protein levels were significantly lower in WSD + Cit-fed mice when compared to
WSD-fed mice only. Protein levels of the tight junction proteins occludin and
zonula occludens-1 in duodenum were significantly lower in mice fed a WSD when
compared to those fed a WSD + Cit (-~70 and -~60 %, respectively, P < 0.05),
whereas portal endotoxin levels, concentration of 3-nitrotyrosine protein adducts
in duodenum and toll-like receptor-4 mRNA expression in livers of WSD + Cit-fed
mice were markedly lower than in WSD-fed mice (-~43 %, P = 0.056; -~80 and -~48
%, respectively, P < 0.05). CONCLUSION: Our data suggest that the protective
effects of supplementing Cit on the development of NAFLD in mice are associated
with a decreased translocation of endotoxin into the portal vein.
PMID- 27496091
TI - Local cholinergic-GABAergic circuitry within the basal forebrain is modulated by
galanin.
AB - The basal forebrain (BF) is an important regulator of hippocampal and cortical
activity. In Alzheimer's disease (AD), there is a significant loss and
dysfunction of cholinergic neurons within the BF, and also a hypertrophy of
fibers containing the neuropeptide galanin. Understanding how galanin interacts
with BF circuitry is critical in determining what role galanin overexpression
plays in the progression of AD. Here, we examined the location and function of
galanin in the medial septum/diagonal band (MS/DBB) region of the BF. We show
that galanin fibers are located throughout the MS/DBB and intermingled with both
cholinergic and GABAergic neurons. Whole-cell patch clamp recordings from MS/DBB
neurons in acute slices reveal that galanin decreases tetrodotoxin-sensitive
spontaneous GABA release and dampens muscarinic receptor-mediated increases in
GABA release in the MS/DBB. These effects are not blocked by pre-exposure to beta
amyloid peptide (Abeta1-42). Optogenetic activation of cholinergic neurons in the
MS/DBB increases GABA release back onto cholinergic neurons, forming a functional
circuit within the MS/DBB. Galanin disrupts this cholinergic-GABAergic circuit by
blocking the cholinergic-induced increase in GABA release. These data suggest
that galanin works in the BF to reduce inhibitory input onto cholinergic neurons
and to prevent cholinergic-induced increase in inhibitory tone. This
disinhibition of cholinergic neurons could serve as a compensatory mechanism to
counteract the loss of cholinergic signaling that occurs during the progression
of AD.
PMID- 27496092
TI - Rate of Organ Space Infection Is Reduced with the Use of an Air Leak Test During
Major Hepatectomies.
AB - BACKGROUND: Organ/space surgical site infections (OSIs) constitute an important
postoperative metric. We sought to assess the impact of a previously described
air leak test (ALT) on the incidence of OSI following major hepatectomies.
METHODS: A single-institution hepatobiliary database was queried for patients who
underwent a major hepatectomy without biliary-enteric anastomosis between January
2009 and June 2015. Demographic, clinicopathologic, and intraoperative data
including application of ALT-were analyzed for associations with postoperative
outcomes, including OSI, hospital length of stay (LOS), morbidity and mortality
rates, and readmission rates. RESULTS: Three hundred eighteen patients were
identified who met inclusion criteria, of whom 210 had an ALT. ALT and non-ALT
patients did not differ in most disease and treatment characteristics, except for
higher rates of trisegmentectomy among ALT patients (53 vs. 34 %, p = 0.002). ALT
patients experienced lower rates of OSI and 90-day morbidity than non-ALT
patients (5.2 vs. 13.0 %, p = 0.015 and 24.8 vs. 40.7 %, p = 0.003,
respectively). In turn, OSI was the strongest independent predictor of longer LOS
(OR = 4.89; 95 % CI, 2.80-6.97) and higher rates of 30- (OR = 32.0; 95 % CI, 10.9
93.8) and 45-day readmissions (OR = 29.4; 95 % CI, 10.2-84.6). CONCLUSIONS: The
use of an intraoperative ALT significantly reduces the rate of OSI following
major hepatectomy and may contribute to lower post-discharge readmission rates.
PMID- 27496093
TI - A BRCA1/2 Mutational Signature and Survival in Ovarian High-Grade Serous
Carcinoma.
AB - BACKGROUND: Mutational signatures have been identified by the broad sequencing of
cancer genomes and reflect underlying processes of mutagenesis. The clinical
application of mutational signatures is not well defined. Here we aim to assess
the prognostic utility of mutational signatures in ovarian high-grade serous
carcinoma. METHODS: Open access data of 15,439 somatic mutations of 310 ovarian
high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) are used to
construct a Bayesian model to classify each cancer as either having or lacking a
BRCA1/2 mutational signature. We evaluate the association of the BRCA1/2
signature with overall survival on the TCGA dataset and on an independent cohort
of 92 ovarian high-grade serous carcinomas from the Australian Ovarian Cancer
Study (AOCS). RESULTS: Patients from TCGA with tumors harboring the BRCA1/2
mutational signature have improved survival (55.2 months vs. 38.0 months), which
is independent of BRCA1/2 gene mutation status, age, stage, and grade (HR = 0.64;
P = 0.02). In the AOCS dataset, the BRCA1/2 mutational signature is also
associated with improved overall survival (46.3 months vs. 23.6 months)
independent of age and stage (HR = 0.52; P = 0.007). CONCLUSIONS: A BRCA1/2
mutational signature is a prognostic marker in ovarian high-grade serous
carcinoma. Mutational signature analysis of ovarian cancer genomes may be useful
in addition to testing for BRCA1/2 mutations. IMPACT: This study identifies the
use of mutational signatures as a biomarker for survival outcome in ovarian high
grade serous carcinoma. Cancer Epidemiol Biomarkers Prev; 25(11); 1511-6. (c)2016
AACR.
PMID- 27496095
TI - An audit of residual cancer burden reproducibility in a UK context.
AB - AIMS: The residual cancer burden score (RCB) is currently the preferred
quantification tool for assessing residual disease following neoadjuvant
chemotherapy (NACT) in breast cancer clinical trials. This has been shown to be
highly reproducible at the MD Anderson Cancer Centre, where it was developed
originally. We wanted to evaluate RCB in a UK context, where macroscopic handling
of tissue may differ between sites. METHODS AND RESULTS: The pathology slides
from 90 post-NACT patients from Guy's and St Thomas' NHS Foundation Trust and the
Royal Bournemouth Hospital were reviewed independently by two specialist breast
histopathologists who recalculated the RCB for each case. Data were collated and
analysed statistically for interobserver reproducibility, for both numerical and
categorical RCB. Overall, agreement between pathologists was 'good' [kappa =
0.775; 95% confidence interval (CI) = 0.668-0.882]. The overall concordance for
continuous RCB score and for categorical RCB group was statistically significant
(Spearman's correlation coefficient = 0.9497; 95% CI = 0.9235-0.9671; P < 0.0001
and Spearman's correlation coefficient = 0.9145; 95% CI = 0.8712-0.9437; P <
0.0001, respectively). Discordance could not be attributed to any one component
of the RCB calculation. CONCLUSIONS: These data suggest that the RCB score is
reproducible in a UK context. Further data comparing it to other quantification
systems is required, however, before any superiority can be established.
PMID- 27496094
TI - Metformin, Diabetes, and Survival among U.S. Veterans with Colorectal Cancer.
AB - BACKGROUND: Metformin has been associated with improved colorectal cancer
survival, but investigations are limited by small numbers of patients and
confounding by diabetic severity. We examined the association between metformin
use and overall survival (OS) in patients with diabetes and colorectal cancer in
a large population of U.S. veterans, while adjusting for measures of diabetic
severity. METHODS: Patients diagnosed with colorectal cancer from January 2001 to
December 2008 were identified from the Veterans Affairs Central Cancer Registry.
Multivariable models were used to examine the adjusted association of OS with
diabetes and use of antidiabetic medications. RESULTS: There were 21,352 patients
diagnosed with colorectal cancer identified (n = 16,355 nondiabetic patients, n =
2,038 diabetic patients on metformin, n = 2,136 diabetic patients on medications
other than metformin, n = 823 diabetic patients not on antidiabetic medication).
Diabetic patients had a significantly worse OS than nondiabetic patients, but
metformin users had only a 10% increase in death (HRadj 1.10; 95% CI, 1.03-1.17,
P = 0.004), as compared with 22% for users of other antidiabetic medications
(HRadj 1.22; 95% CI, 1.15-1.29, P < 0.0001). Among colorectal cancer patients
with diabetes, metformin users had a 13% improved OS versus patients taking other
antidiabetic medications (HRadj 0.87; 95% CI, 0.79-0.95, P = 0.003), while
diabetic patients not on any antidiabetic medications did not differ with respect
to OS (HRadj 1.02; 95% CI, 0.90-1.15, P = 0.76). CONCLUSIONS: Among diabetics
with colorectal cancer, metformin use is associated with improved survival,
despite adjustments for diabetes severity and other risk factors. IMPACT: These
data lend further support to the conduct of randomized studies of possible
anticancer effects of metformin among patients with colorectal cancer. Cancer
Epidemiol Biomarkers Prev; 25(10); 1418-25. (c)2016 AACR.
PMID- 27496097
TI - Council of Europe dismisses claim that abortion in Italy is harder because more
doctors are objecting.
PMID- 27496096
TI - A randomized controlled trial of smoking cessation methods in patients newly
diagnosed with pulmonary tuberculosis.
AB - BACKGROUND: Tuberculosis (TB) and tobacco use are two major alarming global
health issues that tend to be co-prevalent in many developing countries and
various surveys have provided evidence on their entangled associations.
Accordingly, it is strongly suggested that smoking cessation be incorporated in
TB control programs. Therefore, we aimed to evaluate the effectiveness of two
smoking cessation methods among newly-diagnosed pulmonary TB patients. METHODS: A
total of 210 newly-diagnosed pulmonary TB patients from Tehran, Iran with smoking
habits were included in this randomized clinical trial during 2012-2013. Patients
were assigned to three groups of control (just TB medical treatment), brief
advice (TB medical treatment plus individualized counseling sessions of quitting
behavioral therapy) and combined intervention (TB medical treatment plus
individualized counseling sessions of quitting behavioral therapy plus medical
treatment with slow release bupropion). Patients' abstinence was followed at six
time point during six months. Data were analyzed by SPSS v.22 using Generalized
Estimating Equations (GEE) model. RESULTS: Abstinance rate at the end of six
months were 71.7 % for combined intervention group, 33.9 % for brief advice group
and 9.8 % for the control group (p < 0.001). Combined intervention group and
brief advice group respectively had 35 times (p < 0.001, OR = 35.26, 95 % CI =
13.77-90.32) and 7 times (p < 0.001, OR = 7.14, 95 % CI = 2.72-18.72) more odds
of not being an active smoker at each time point, compared to the control group.
CONCLUSION: Considering the prevalence and importance of TB and the substantial
influence of these preventive measures on controlling tobacco use, application of
such programs is recommended. TRIAL REGISTRATION: The survey was registered in
the Iranian registry of clinical trials website (irct.ir) in August 31, 2013 with
IRCT ID: IRCT2013062613783N1 .
PMID- 27496098
TI - To belong or not to belong: nursing students' interactions with clinical learning
environments - an observational study.
AB - BACKGROUND: Belongingness has been argued to be a prerequisite for students'
learning in the clinical setting but making students feel like they belong to the
workplace is a challenge. From a sociocultural perspective, workplace
participatory practices is a framework that views clinical learning environments
to be created in interaction between students and the workplace and hence, are
dependent on them both. The aim of this study was to explore the interdependence
between affordances and engagement in clinical learning environments. The
research question was: How are nursing students influenced in their interactions
with clinical learning environments? METHODS: An observational study with field
observations and follow-up interviews was performed. The study setting comprised
three academic teaching hospitals. Field observations included shadowing
undergraduate nursing students during entire shifts. Fifty-five hours of field
observations and ten follow-up interviews with students, supervisors and clinical
managers formed the study data. A thematic approach to the analysis was taken and
performed iteratively with the data collection. RESULTS: The results revealed
that students strived to fill out the role they were offered in an aspirational
way but that they became overwhelmed when given the responsibility of care. When
students' basic values did not align with those enacted by the workplace, they
were not willing to compromise their own values. Workplaces succeeded in inviting
students into the community of nurses and the practice of care. Students
demonstrated hesitance regarding their desire to belong to the workplace
community. CONCLUSION: The results imply that the challenge for clinical
education is not to increase the experience of belongingness but to maintain
students' critical and reflective approach to health care practice. Additionally,
results suggest students to be included as an important stakeholder in creating
clinical learning environments rather than being viewed as consumer of clinical
education.
PMID- 27496102
TI - Chilo iridescent virus (CIV) ORF 012L encodes a protein with both exonuclease and
endonuclease functions.
AB - Chilo iridescent virus (CIV) is the type member of the genus Iridovirus within
the family Iridoviridae. The virions of CIV contain a single linear dsDNA
molecule that is circularly permuted and terminally redundant. The genome of CIV
contains an open reading frame (ORF 012L) encoding a protein homologous to
exonuclease II of Schizosaccharomyces pombe. In this study, we focused on the
characterization of CIV ORF 012L. The target ORF was cloned into the pET28a
vector, expressed in E. coli strain BL21 (DE3) pLysS with an N-terminal His tag
and purified to homogeneity by using Ni-NTA affinity chromatography. Biochemical
characterization of the purified CIV 012L confirmed that this viral protein is a
functional 5'-3' exonuclease that digests 3'-biotin-labelled oligonucleotides and
linear double-stranded DNA (dsDNA) molecules from their 5' termini in a highly
processive manner. CIV 012L also has a potent endonuclease activity on dsDNA in
vitro. In addition, CIV 012L converted supercoiled plasmid DNA (replicative form
I, RFI) into the open circular form (RFII) and then open circular form into
linear form (RFIII). Endonuclease activity of CIV 012L was optimal in the
presence of 10 mM Mg(2+) or 30 mM Mn(2+) ions and at 150 mM NaCl or KCl salt
concentrations. The highest endonuclease activity was obtained at pH 8, and it
reached a maximum at 55 degrees C. The CIV 012L protein showed deficiencies for
both double- and single-stranded RNAs.
PMID- 27496101
TI - Evidence for chemokine synergy during neutrophil migration in ARDS.
AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening
condition characterised by pulmonary oedema, respiratory failure and severe
inflammation. ARDS is further characterised by the recruitment of neutrophils
into the lung interstitium and alveolar space. OBJECTIVES: The factors that
regulate neutrophil infiltration into the inflamed lung and our understanding of
the pathomechanisms in ARDS remain incomplete. This study aimed at determining
the role of the chemokine (C-C motif) ligand (CCL)2 and CCL7 in ARDS. METHODS:
CCL2 and CCL7 protein levels were measured in bronchoalveolar lavage (BAL) fluid
obtained from lipopolysaccharide(LPS)-challenged human volunteers and two
separate cohorts of patients with ARDS. Neutrophil chemotaxis to ARDS BAL fluid
was evaluated and the contribution of each was assessed and compared with
chemokine (C-X-C motif) ligand 8 (CXCL8). Chemokine receptor expression on
neutrophils from blood or BAL fluid of patients with ARDS was analysed by flow
cytometry. RESULTS: CCL2 and CCL7 were significantly elevated in BAL fluid
recovered from LPS-challenged volunteers and patients with ARDS. BAL fluid from
patients with ARDS was highly chemotactic for human neutrophils and neutralising
either CCL2 or CCL7 attenuated the neutrophil chemotactic response. Moreover,
CCL2 and CCL7 synergised with CXCL8 to promote neutrophil migration. Furthermore,
neutrophils isolated from the blood or BAL fluid differentially regulated the
cell surface expression of chemokine (C-X-C motif) receptor 1 and C-C chemokine
receptor type 2 during ARDS. CONCLUSION: This study highlights important
inflammatory chemokines involved in regulating neutrophil migration, which may
have potential value as therapeutic targets for the treatment of ARDS.
PMID- 27496100
TI - Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto
Kakizaki rats.
AB - BACKGROUND: There is a spectacular rise in the global prevalence of type 2
diabetes mellitus (T2DM) due to the worldwide obesity epidemic. However, a
significant proportion of T2DM patients are non-obese and they also have an
increased risk of cardiovascular diseases. As the Goto-Kakizaki (GK) rat is a
well-known model of non-obese T2DM, the goal of this study was to investigate the
effect of non-obese T2DM on cardiac alterations of the transcriptome in GK rats.
METHODS: Fasting blood glucose, serum insulin and cholesterol levels were
measured at 7, 11, and 15 weeks of age in male GK and control rats. Oral glucose
tolerance test and pancreatic insulin level measurements were performed at 11
weeks of age. At week 15, total RNA was isolated from the myocardium and assayed
by rat oligonucleotide microarray for 41,012 genes, and then expression of
selected genes was confirmed by qRT-PCR. Gene ontology and protein-protein
network analyses were performed to demonstrate potentially characteristic gene
alterations and key genes in non-obese T2DM. RESULTS: Fasting blood glucose,
serum insulin and cholesterol levels were significantly increased, glucose
tolerance and insulin sensitivity were significantly impaired in GK rats as
compared to controls. In hearts of GK rats, 204 genes showed significant up
regulation and 303 genes showed down-regulation as compared to controls according
to microarray analysis. Genes with significantly altered expression in the heart
due to non-obese T2DM includes functional clusters of metabolism (e.g. Cyp2e1,
Akr1b10), signal transduction (e.g. Dpp4, Stat3), receptors and ion channels
(e.g. Sln, Chrng), membrane and structural proteins (e.g. Tnni1, Mylk2, Col8a1,
Adam33), cell growth and differentiation (e.g. Gpc3, Jund), immune response (e.g.
C3, C4a), and others (e.g. Lrp8, Msln, Klkc1, Epn3). Gene ontology analysis
revealed several significantly enriched functional inter-relationships between
genes influenced by non-obese T2DM. Protein-protein interaction analysis
demonstrated that Stat is a potential key gene influenced by non-obese T2DM.
CONCLUSIONS: Non-obese T2DM alters cardiac gene expression profile. The altered
genes may be involved in the development of cardiac pathologies and could be
potential therapeutic targets in non-obese T2DM.
PMID- 27496103
TI - The Effect of Energy Labelling on Menus and a Social Marketing Campaign on Food
Purchasing Behaviours of University Students.
AB - BACKGROUND: This study assessed the impact of kilojoule (kJ) labelling alone or
accompanied by a social marketing campaign on food sales and selection of less
energy-dense meals by young adults from a university food outlet. METHODS: There
were two kJ labelling intervention phases each of five weeks: (1) kJ labelling
alone (2) kJ labels with marketing materials ("8700 kJ campaign"). Food sales of
labelled items were tracked during each intervention and five weeks after. Food
sales during interventions were also compared with historical sales of foods in
the same 10-week period in the previous year. A sub sample of young adults (n =
713; aged 19-24) were surveyed during both the interventions to assess awareness,
influence, sentiment and anticipated future impact of kJ labels and the social
marketing campaign respectively. RESULTS: There were no differences in sales
between the kJ labelling with social marketing and the 5-weeks of labelling
before and after. The percentage sale of chicken Caesar burger (3580 kJ, P =
0.01), steak and chips (4000 kJ, P = 0.02) and the grill burger (5500 kJ, P =
0.00) were lower in the year with menu labelling and social marketing campaign.
Only 30 % students were initially aware of the kJ labels on the menu but 75 % of
students were accepting of kJ labelling, after they were made aware. Respondents
viewing the marketing campaign elements and then using kJ values on the menu
selected meals with a lower mean energy content; constituting a reduction of 978
kJ (p < 0.01) even though the majority claimed that the 8700 kJ campaign would
not impact their food choices. CONCLUSIONS: Point-of-purchase energy labelling
may be an effective method to encourage better food choices when eating out among
young adults. However, further efforts to increase awareness and provide
education about energy requirements to prevent weight gain will be needed.
PMID- 27496104
TI - A gain-of-function mutation in Nav1.6 in a case of trigeminal neuralgia.
AB - Idiopathic trigeminal neuralgia (TN) is a debilitating pain disorder
characterized by episodic unilateral facial pain along the territory of branches
of the trigeminal nerve. Human painful disorders, but not TN, have been linked to
gain-of-function mutations in peripheral voltage-gated sodium channels (NaV1.7,
NaV1.8 and NaV1.9). Gain-of-function mutations in NaV1.6, which is expressed in
myelinated and unmyelinated CNS and peripheral nervous system neurons and
supports neuronal high-frequency firing, have been linked to epilepsy but not to
pain. Here, we describe an individual who presented with evoked and spontaneous
paroxysmal unilateral facial pain, and carried a diagnosis of TN. Magnetic
resonance imaging showed unilateral neurovascular compression, consistent with
pain in areas innervated by the second branch of the trigeminal nerve. Genetic
analysis as part of a phase 2 clinical study in patients with TN conducted by
Convergence Pharmaceuticals Ltd revealed a previously undescribed de novo
missense mutation in NaV1.6 (c.A406G; p.Met136Val). Whole-cell voltage-clamp
recordings show that the Met136Val mutation significantly increases peak current
density (1.5-fold) and resurgent current (1.6-fold) without altering gating
properties. Current-clamp studies in trigeminal ganglion (TRG) neurons showed
that Met136Val increased the fraction of high-firing neurons, lowered the current
threshold and increased the frequency of evoked action potentials in response to
graded stimuli. Our results demonstrate a novel NaV1.6 mutation in TN, and show
that this mutation potentiates transient and resurgent sodium currents and leads
to increased excitability in TRG neurons. We suggest that this gain-of-function
NaV1.6 mutation may exacerbate the pathophysiology of vascular compression and
contribute to TN.
PMID- 27496106
TI - Genetically Confirmed Neonatal Diabetes: A Single Centre Experience.
PMID- 27496105
TI - Rationale and design of the multicenter randomized trial investigating the
effects of levosimendan pretreatment in patients with low ejection fraction (<=40
%) undergoing CABG with cardiopulmonary bypass (LICORN study).
AB - BACKGROUND: Patients with a left ventricular ejection fraction (LVEF) of less
than 40 % are at high risk of developing postoperative low cardiac output
syndrome (LCOS). Despite actual treatments (inotropic agents and/or mechanical
assist devices), the mortality rate of such patients remains very high (13 to 24
%). The LICORN trial aims at assessing the efficacy of a preoperative infusion of
levosimendan in reducing postoperative LCOS in patients with poor LVEF undergoing
coronary artery bypass grafting (CABG). METHODS/DESIGN: LICORN study is a
multicenter, randomized double-blind, placebo-controlled trial in parallel
groups. 340 patients with LVEF <=40 %, undergoing CABG will be recruited from 13
French hospitals. The study drug will be started after anaesthesia induction and
infused over 24 h (0.1 MUg/kg/min). The primary outcome (postoperative LCOS) is
evaluated using a composite criterion composed of: 1) need for inotropic agents
beyond 24 h following discontinuation of the study drug; 2) need for post
operative mechanical assist devices or failure to wean from these techniques when
inserted pre-operatively; 3) need for renal replacement therapy. Secondary
outcomes include: 1) mortality at Day 28 and Day 180; 2) each item of the
composite criterion of the primary outcome; 3) the number of "ventilator-free"
days and "out of intensive care unit" days at Day 28. DISCUSSION: The usefulness
of levosimendan in the perioperative period has not yet been documented with a
high level of evidence. The LICORN study is the first randomized controlled trial
evaluating the clinical value of preoperative levosimendan in high risk cardiac
surgical patients undergoing CABG. TRIAL REGISTRATION NUMBER: NCT02184819
(ClinicalTrials.gov).
PMID- 27496107
TI - I'll Have Another Shot, Please!
PMID- 27496108
TI - Immunotherapy for Lung Cancer: Many Questions Yet to Be Answered.
PMID- 27496109
TI - Donor-Derived T-Cell Large Granular Lymphocytic Leukemia in a Patient With
Peripheral T-Cell Lymphoma.
AB - T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell
transplantation (SCT) is rare and its natural history and clinical outcome have
not been well described. We report the clinical, morphologic, immunophenotypic,
and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old
man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise
specified (PTCL-NOS). The patient presented with persistent neutropenia and
splenomegaly 9 months after SCT when the chimerism study showed a 100% donor
pattern. A splenectomy revealed T-LGL leukemia. Flow cytometric analysis showed
an aberrant T-cell population positive for CD3, CD5 (dim, subset), CD7, CD8, CD16
(subset), CD57, CD94 (dim, partial), and T-cell receptor (TCR) alphabeta, and
negative for CD4, CD26, CD56, and TCRgammadelta. Molecular studies showed
monoclonal TCRbeta and TCRgamma gene rearrangements. Both the immunophenotype and
molecular profile of the T-LGL leukemia were different from the pre-SCT PTCL.
Sequencing analysis for STAT3 exon 21 did not reveal any mutation in both pre-SCT
and post-SCT specimens. The patient did not receive any treatment for T-LGL
leukemia; however, his count progressively increased after splenectomy, despite
the presence of persistent T-LGL leukemia in the bone marrow. There was no
evidence of recurrent PTCL. We propose an algorithm to diagnose this rare post
SCT neoplasm.
PMID- 27496110
TI - NCCN Guidelines Insights: Melanoma, Version 3.2016.
AB - The NCCN Guidelines for Melanoma have been significantly revised over the past
few years in response to emerging data on a number of novel agents and treatment
regimens. These NCCN Guidelines Insights summarize the data and rationale
supporting extensive changes to the recommendations for systemic therapy in
patients with metastatic or unresectable melanoma.
PMID- 27496111
TI - NCCN's Commitment to Medication Safety: The Vincristine Initiative.
AB - The mission of NCCN is to improve the quality, effectiveness, and efficiency of
cancer care so that patients can live better lives. Improving medication safety
is an important aspect of fulfilling this mission. In September 2014, the NCCN
Best Practices Committee began a medication safety initiative to improve the safe
use of vincristine. This article describes and discusses this initiative.
PMID- 27496112
TI - NCCN Framework for Resource Stratification: A Framework for Providing and
Improving Global Quality Oncology Care.
AB - More than 14 million new cancer cases and 8.2 million cancer deaths are estimated
to occur worldwide on an annual basis. Of these, 57% of new cancer cases and 65%
of cancer deaths occur in low- and middle-income countries. Disparities in
available resources for health care are enormous and staggering. The WHO
estimates that the United States and Canada have 10% of the global burden of
disease, 37% of the world's health workers, and more than 50% of the world's
financial resources for health; by contrast, the African region has 24% of the
global burden of disease, 3% of health workers, and less than 1% of the world's
financial resources for health. This disparity is even more extreme with cancer.
NCCN has developed a framework for stratifying the NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines) to help health care systems in providing
optimal care for patients with cancer with varying available resources. This
framework is modified from a method developed by the Breast Health Global
Initiative. The NCCN Framework for Resource Stratification (NCCN Framework)
identifies 4 resource environments: basic resources, core resources, enhanced
resources, and NCCN Guidelines, and presents the recommendations in a graphic
format that always maintains the context of the NCCN Guidelines. This article
describes the rationale for resource-stratified guidelines and the methodology
for developing the NCCN Framework, using a portion of the NCCN Cervical Cancer
Guideline as an example.
PMID- 27496113
TI - Wealth, Health Expenditure, and Cancer: A National Perspective.
AB - BACKGROUND: The US health care system is characterized by high health
expenditures with penultimate outcomes. This ecological study evaluates the
associations between wealth, health expenditure, and cancer outcomes at the state
level. METHODS: We extracted gross domestic product (GDP) and health expenditure
per capita from the 2009 Bureau of Economic Analysis and the Centers for Medicare
& Medicaid Services, respectively. Using data from the NCI, we retrieved
colorectal cancer (CRC), breast cancer, and all-cancer age-adjusted rates and
computed mortality/incidence (M/I) ratios. We used the Spearman's rank
correlation to determine the association between the financial indicators and
cancer outcomes, and we constructed geographic distribution maps to describe
these associations. RESULTS: GDP per capita significantly correlated with lower
M/I ratios for all cancers, breast cancer, and CRC. As for health expenditure per
capita, preliminary analysis highlighted a rift between the Northeastern and
Southern states, which translated into worse breast and all-cancer outcomes in
Southern states. Further analysis showed that higher health expenditure
significantly correlated with decreased breast cancer M/I ratio. However, CRC
outcomes were not significantly affected by health expenditure, nor were all
cancer outcomes. CONCLUSIONS: All cancers, breast cancer, and CRC outcomes
significantly correlated with wealth, whereas only breast cancer correlated with
higher health expenditure. Future research is needed to evaluate the potential
role of policies in optimizing resource allocation in the states' efforts against
CRC and minimizing disparities in interstate cancer outcomes.
PMID- 27496114
TI - Predictors of In-Hospital Mortality in Patients With Metastatic Cancer Receiving
Specific Critical Care Therapies.
AB - BACKGROUND: In-hospital mortality is high for critically ill patients with
metastatic cancer. To help patients, families, and clinicians make an informed
decision about invasive medical treatments, we examined predictors of in-hospital
mortality among patients with metastatic cancer who received critical care
therapies (CCTs). PATIENTS AND METHODS: We used the 2010 California Healthcare
Cost and Utilization Project: State Inpatient Databases to identify admissions of
patients with metastatic cancer (age >=18 years) who received CCTs, including
invasive mechanical ventilation (IMV), tracheostomy, percutaneous endoscopic
gastrostomy (PEG) tube, acute use of dialysis, and total parenteral nutrition
(TPN). We first described the characteristics and outcomes of patients who
received any CCTs. We then used multivariable logistic regression models with
generalized estimating equations (to account for clustering within hospitals) to
identify predictors of in-hospital mortality among patients who received any
CCTs. RESULTS: For 2010, we identified 99,085 admissions among patients with
metastatic cancer. Of these, 9,348 (9.4%) received any CCT during
hospitalization; 50% received IMV, 15% PEG tube, 8% tracheostomy, 40% TPN, and 8%
acute dialysis. Inpatient mortality was 30%. Of patients who received any CCT and
survived to discharge, 27% were discharged to a skilled nursing facility.
Compared with patients who died, costs of care were $3,019 higher for admissions
in which patients survived the hospitalization. Predictors of in-hospital
mortality included non-white race (vs whites), lack of insurance (vs Medicare),
unscheduled admissions, principal diagnosis of infections (vs cancer-related),
greater burden of comorbidities, end-stage renal disease, liver disease and lung
cancer (vs other cancers). CONCLUSIONS: Although more studies are needed to
better understand risks and benefits of specific treatments in the setting of
specific cancer types, these data will help to inform decision-making for
patients with metastatic cancer who become critically ill.
PMID- 27496115
TI - Is Advanced Imaging in Early-Stage Breast Cancer Ever Warranted? Reconciling
Clinical Judgment With Common Quality Measures.
AB - BACKGROUND: The American Board of Internal Medicine Foundation's Choosing Wisely
initiative aims to reduce unnecessary advanced imaging for early-stage breast
cancer (ESBC). Additionally, NCCN Clinical Practice Guidelines in Oncology for
Breast Cancer permit such images when oncologists perceive clinical clues of
advanced disease. The utility of advanced imaging in ESBC is not known. PATIENTS
AND METHODS: We analyzed all patients with ESBC from January 2010 to June 2012 at
a large tertiary cancer center. Early-stage was defined as stage IIb or less. We
included advanced imaging within 60 days after diagnosis. Three independent
reviewers manually abstracted a sample of charts to determine reason for
ordering. RESULTS: A total of 1,143 ESBC cases were identified; 21.8% of which
had at least one advanced imaging procedure performed. Imaging modalities varied
widely (38% CT, 21% PET, 34% bone scans, and 6% MRI). Patients who underwent
advanced imaging were more likely to have triple-negative disease, be younger
(age <50 years), and have higher stage disease (stage IIb vs <= stage IIa; all
P<.001). A total of 100 cases (40%) were abstracted; 5 were excluded due to
bilateral disease. Of the 95 cases remaining, 62% of the imaging studies were
performed for staging, 17% for significant concurrent disease, and 22% for
findings atypical of ESBC. Of the studies performed for staging, 15% produced
clinically meaningful findings. Overall, 45% of studies were ordered for
suspicious findings, complex history, or produced a meaningful result.
CONCLUSIONS: Of patients with ESBC, 21.8% had at least one advanced imaging
procedure within 60 days of diagnosis; almost half were clinically useful. Chart
abstraction helped clarify intent. Conversations between clinicians and patients
are needed to balance patient preferences and clinician judgment.
PMID- 27496117
TI - Genetic/Familial High-Risk Assessment: Colorectal Version 1.2016, NCCN Clinical
Practice Guidelines in Oncology.
AB - This is a focused update highlighting the most current NCCN Guidelines for
diagnosis and management of Lynch syndrome. Lynch syndrome is the most common
cause of hereditary colorectal cancer, usually resulting from a germline mutation
in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in
the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime
risk, compared with the general population, for colorectal cancer, endometrial
cancer, and other cancers, including of the stomach and ovary. As of 2016, the
panel recommends screening all patients with colorectal cancer for Lynch syndrome
and provides recommendations for surveillance for early detection and prevention
of Lynch syndrome-associated cancers.
PMID- 27496118
TI - Biomarkers in Colorectal Cancer Screening.
AB - Colorectal cancer (CRC) is the third most common cause of cancer death in men and
women in the United States. The main goals of screening are to prevent
carcinogenesis (via adenoma detection and removal) and detect cancer at an early,
curable stage. CRC mortality is steadily dropping in the United States, partly
because of greater screening utilization. However, nearly 1 in 3 average-risk
people are not up to date with standard CRC screening recommendations. This
review surveys a wide range of CRC biomarkers in various stages of development,
which may offer attractive risk stratification tools; a few have reached the
commercial stage. If widely accepted, these tools may contribute to shift CRC
screening practices away from 1-step colonoscopy to a 2-step risk stratification
process of predictive biomarker measurements followed by colonoscopy for lower
risk patients with a positive result. Such strategies could potentially increase
the rate of CRC screening.
PMID- 27496116
TI - Associations Between End-of-Life Cancer Care Patterns and Medicare Expenditures.
AB - BACKGROUND: The purpose of this study was to examine the extent to which patterns
of intensive end-of-life care explain geographic variation in end-of-life care
expenditures among cancer decedents. METHODS: Using the SEER-Medicare database,
we identified 90,465 decedents who were diagnosed with cancer in 2004-2011.
Measures of intensive end-of-life care included chemotherapy received within 14
days of death; more than 1 emergency department visit, more than 1
hospitalization, or 1 or more intensive care unit (ICU) admissions within 30 days
of death; in-hospital death; and hospice enrollment less than 3 days before
death. Using hierarchical generalized linear models, we estimated risk-adjusted
expenditures in the last month of life for each hospital referral region and
identified key contributors to variation in expenditures. RESULTS: The mean
expenditure per cancer decedent in the last month of life was $10,800, ranging
from $8,300 to $15,400 in the lowest and highest expenditure quintile areas,
respectively. There was considerable variation in the percentage of decedents
receiving intensive end-of-life care intervention, with 41.7% of decedents
receiving intensive care in the lowest quintile of expenditures versus 57.9% in
the highest quintile. Regional patterns of late chemotherapy or late hospice use
explained only approximately 1% of the expenditure difference between the highest
and lowest quintile areas. In contrast, the proportion of decedents who had ICU
admissions within 30 days of death was a major driver of variation, explaining
37.6% of the expenditure difference. CONCLUSIONS: Promoting appropriate end-of
life care has the potential to reduce geographic variation in end-of-life care
expenditures.
PMID- 27496119
TI - Point: The Power of Data to (Mis)Guide Policy to Improve Cancer Health Equity.
PMID- 27496120
TI - Counterpoint: Wealth, Health Expenditure, and Cancer-Translating Research Into
Efficient Policies.
PMID- 27496123
TI - Taq1B Polymorphism of Cholesteryl Ester Transfer Protein (CETP) and Its Effects
on the Serum Lipid Levels in Metabolic Syndrome Patients.
AB - The metabolic syndrome (MetS) is one of the most important risk factors for type
2 diabetes and cardiovascular disease. This syndrome is characterized by
abdominal obesity, hypertension, insulin resistance, and dyslipidemia. The plasma
origin of Cholesteryl ester transfer protein (CETP) is responsible for
transferring cholesterol esters from high-density lipoprotein particles to
apolipoprotein B containing lipoproteins compartment. We conducted this study to
investigate the association between CETP gene Taq1B (rs708272) polymorphism in
the metabolic syndrome among Iranian subjects. A sample size of 200 patients
diagnosed with MetS together with 200 healthy donors as control were enrolled in
this study. The investigation of polymorphism was performed by the use of
polymerase chain reaction and restriction fragment length polymorphism analysis.
To determine the relationship between polymorphism and lipid profile, we measured
lipids and CETP concentration in metabolic syndrome and control subjects.
Genotype distribution and allelic frequencies of polymorphism were determined and
compared in both groups. Our findings showed that all clinical and biochemical
characteristics in patients differed from the control group. The results showed
that genotype and allele frequency of the Taq1B polymorphism was not
significantly different between two groups. Instinctively, CETP was significantly
higher in metabolic syndrome (1.64 +/- 0.32 ug/ml) than in control (1.53 +/- 0.34
ug/ml). A low level of CETP was found in blood of B2B2 typified genotype. In
spite of Taq1B polymorphism on ester transfer protein concentration, no direct
correlation was found between this polymorphism and metabolic syndrome.
PMID- 27496122
TI - Factors Associated with Interest in Gene-Panel Testing and Risk Communication
Preferences in Women from BRCA1/2 Negative Families.
AB - Scientific advances have allowed the development of multiplex gene-panels to
assess many genes simultaneously in women who have tested negative for BRCA1/2.
We examined correlates of interest in testing for genes that confer modest and
moderate breast cancer risk and risk communication preferences for women from
BRCA negative families. Female first-degree relatives of breast cancer patients
who tested negative for BRCA1/2 mutations (N = 149) completed a survey assessing
multiplex genetic testing interest and risk communication preferences. Interest
in testing was high (70 %) and even higher if results could guide risk-reducing
behavior changes such as taking medications (79 %). Participants preferred to
receive genomic risk communications from a variety of sources including: primary
care physicians (83 %), genetic counselors (78 %), printed materials (71 %) and
the web (60 %). Factors that were independently associated with testing interest
were: perceived lifetime risk of developing cancer (odds ratio (OR) = 1.67: 95 %
confidence interval (CI) 1.06-2.65) and high cancer worry (OR = 3.12: CI 1.28
7.60). Findings suggest that women from BRCA1/2 negative families are a unique
population and may be primed for behavior change. Findings also provide guidance
for clinicians who can help develop genomic risk communications, promote informed
decision making and customize behavioral interventions.
PMID- 27496124
TI - Passive immunization does not provide protection against experimental infection
with Mycoplasma haemofelis.
AB - Mycoplasma haemofelis (Mhf) is the most pathogenic feline hemotropic mycoplasma.
Cats infected with Mhf that clear bacteremia are protected from Mhf reinfection,
but the mechanisms of protective immunity are unresolved. In the present study we
investigated whether the passive transfer of antibodies from Mhf-recovered cats
to naive recipient cats provided protection against bacteremia and clinical
disease following homologous challenge with Mhf; moreover, we characterized the
immune response in the recipient cats. Ten specified pathogen-free (SPF) cats
were transfused with pooled plasma from cats that had cleared Mhf bacteremia;
five control cats received plasma from naive SPF cats. After homologous challenge
with Mhf, cats were monitored for 100 days using quantitative PCR, hematology,
blood biochemistry, Coombs testing, flow cytometry, DnaK ELISA, and red blood
cell (RBC) osmotic fragility (OF) measurement. Passively immunized cats were not
protected against Mhf infection but, compared to control cats, showed
significantly higher RBC OF and B lymphocyte (CD45R/B220(+)) counts and
occasionally higher lymphocyte, monocyte and activated CD4(+) T lymphocyte
(CD4(+)CD25(+)) counts; they also showed higher bilirubin, total protein and
globulin levels compared to those of control cats. At times of peak bacteremia, a
decrease in eosinophils and lymphocytes, as well as subsets thereof (B
lymphocytes and CD5(+), CD4(+) and CD8(+) T lymphocytes), and an increase in
monocytes were particularly significant in the passively immunized cats. In
conclusion, passive immunization does not prevent bacteremia and clinical disease
following homologous challenge with Mhf, but enhances RBC osmotic fragility and
induces a pronounced immune response.
PMID- 27496125
TI - Comparison of methods for the identification of microorganisms isolated from
blood cultures.
AB - BACKGROUND: Bloodstream infections are responsible for thousands of deaths each
year. The rapid identification of the microorganisms causing these infections
permits correct therapeutic management that will improve the prognosis of the
patient. In an attempt to reduce the time spent on this step, microorganism
identification devices have been developed, including the VITEK((r)) 2 system,
which is currently used in routine clinical microbiology laboratories. METHODS:
This study evaluated the accuracy of the VITEK((r)) 2 system in the
identification of 400 microorganisms isolated from blood cultures and compared
the results to those obtained with conventional phenotypic and genotypic methods.
In parallel to the phenotypic identification methods, the DNA of these
microorganisms was extracted directly from the blood culture bottles for
genotypic identification by the polymerase chain reaction (PCR) and DNA
sequencing. RESULTS: The automated VITEK((r)) 2 system correctly identified 94.7
% (379/400) of the isolates. The YST and GN cards resulted in 100 % correct
identifications of yeasts (15/15) and Gram-negative bacilli (165/165),
respectively. The GP card correctly identified 92.6 % (199/215) of Gram-positive
cocci, while the ANC card was unable to correctly identify any Gram-positive
bacilli (0/5). CONCLUSIONS: The performance of the VITEK((r)) 2 system was
considered acceptable and statistical analysis showed that the system is a
suitable option for routine clinical microbiology laboratories to identify
different microorganisms.
PMID- 27496127
TI - Ultrasonography for the assessment of lung recruitment maneuvers.
AB - Lung collapse is a known complication that affects most of the patients
undergoing positive pressure mechanical ventilation. Such atelectasis and airways
closure lead to gas exchange and lung mechanics impairment and has the potential
to develop an inflammatory response in the lungs. These negative effects of lung
collapse can be reverted by a lung recruitment maneuver (RM) i.e. a ventilatory
strategy that resolves lung collapse by a brief and controlled increment in
airway pressures. However, an unsolved question is how to assess such RM at the
bedside. The aim of this paper is to describe the usefulness of lung sonography
(LUS) to conduct and personalize RM in a real-time way at the bedside. LUS has
favorable features to assess lung recruitment due to its high specificity and
sensitivity to detect lung collapse together with its non-invasiveness,
availability and simple use.
PMID- 27496126
TI - The efficacy of Cognitive training in patients with VAsCular Cognitive
Impairment, No dEmentia (the Cog-VACCINE study): study protocol for a randomized
controlled trial.
AB - BACKGROUND: Vascular cognitive impairment, no dementia (VCIND) refers to
cognitive deficits associated with underlying vascular causes that fall short of
a dementia diagnosis. There is currently no treatment for VCIND. Computerized
cognitive training, which has significantly improved cognitive function in
healthy older adults and patients with cognitive impairment has not yet been
applied to VCIND. METHODS/DESIGN: The proposed study is a three-center, double
blinded, randomized controlled trial that will include 60 patients with VCIND.
The patients will be randomized to either a training or a control group. The
intervention is internet-based cognitive training performed for 30 min over 35
sessions. Neuropsychological assessment and functional and structural MRI will be
performed before and after 7 weeks training. Primary outcomes are global
cognitive function and executive function. Secondary outcome measures are
neuroplasticity changes measured by functional and structural MRI. DISCUSSION:
Applying an internet-based, multi-domain, adaptive program, this study aims to
assess whether cognitive training improves cognitive abilities and neural
plasticity in patients with subcortical VCIND. In addition to the comprehensive
assessment of the participants by neuropsychological tests, cerebrovascular risk
factors and apolipoprotein E genotyping, neuroplasticity will be used as an
evaluation outcome in this study for, to our knowledge, the first time. The
combination of functional and structural MRI and neuropsychological tests will
have strong sensitivity in evaluating the effects of cognitive training and will
also reveal the underlying mechanisms at work. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02640716 . Retrospectively registered on 21 December 2015.
PMID- 27496128
TI - Genome-wide association study revealed genomic regions related to white/red
earlobe color trait in the Rhode Island Red chickens.
AB - BACKGROUND: Earlobe color is a naturally and artificially selected trait in
chicken. As a head furnishing trait, it has been selected as a breed
characteristic. Research has demonstrated that white/red earlobe color was
related to at least three loci and sex-linked. However, there has been little
work to date to identify the specific genomic regions and genes response to
earlobe color in Rhode Island Red chickens. Currently, it is possible to identify
the genomic regions responsible for white/red earlobe in Rhode Island Red chicken
to eliminate this gap in knowledge by using genome-wide association (GWA)
analysis. RESULTS: In the present study, genome-wide association (GWA) analysis
was conducted to explore the candidate genomic regions response to chicken
earlobe color phenotype. Hens with red dominant and white dominant earlobe was
used for case-control analysis by Illumina 600 K SNP arrays. The GWA results
showed that 2.38 Mb genomic region (50.13 to 52.51 Mb) with 282 SNPs on
chromosome Z were significantly correlated to earlobe color, including sixteen
known genes and seven anonymous genes. The sixteen genes were PAM, SLCO4C1,
ST8SIA4, FAM174A, CHD1, RGMB, RIOK2, LIX1, LNPEP, SHB, RNF38, TRIM14, NANS, CLTA,
GNE, and CPLX1. CONCLUSIONS: The study has revealed the white/red earlobe trait
is polygenic and sex-linked in Rhode Island Red chickens. In the genome
significant ~2.38 Mb region, twenty-three genes were found and some of them could
play critical roles in the formation of white/red earlobe color, especially gene
SLCO4C1. Taken together, the candidate genes findings herein can help elucidate
the genomic architecture of response to white/red earlobe and provide a new
insight on mechanisms underlying earlobe color in Rhode Island Red chickens and
other breeds.
PMID- 27496129
TI - Five minutes with . . . Jenny Higham, chair of the Medical Schools Council.
PMID- 27496130
TI - Incidence and excess mortality of hip fracture in young adults: a nationwide
population-based cohort study.
AB - BACKGROUND: This study assessed the incidence and excess mortality of hip
fractures among inpatients aged 20-40 years in a nationwide population database
in Taiwan. METHODS: Subjects were selected from Taiwan's National Health
Insurance Research Database for the period 2001-2008 and were followed up until
the end of 2010. A total of 4,523 subjects were admitted for the first time with
primary diagnosis of hip fracture and treated with operation. RESULTS: The
overall annual incidence, mortality, and standardized mortality ratio (SMR)
decreased from 7.68 to 7.23 per 100,000, from 1.37 % to 0.94 %, and from 9.06 to
6.71, respectively, from 2001 to 2008. The 1-year, 2-year, 3-year, 5-year, and 10
year mortality rates were 1.28 %, 2.44 %, 3.54 %, 5.32 %, and 10.50 %,
respectively for the whole cohort. The 1-year, 2-year, 3-year, 5-year, and 10
year SMRs were 8.33, 7.59, 7.28, 6.39, and 5.82, respectively, for the whole
cohort. Risk factors for overall death were male gender, trochanteric fracture,
hemiarthroplasty, and higher Charlson comorbidity index (CCI) scores.
CONCLUSIONS: The high SMRs found in the present study suggest that young adults
with former hip fracture should be closely followed up to prevent early
mortality.
PMID- 27496131
TI - Occurrence and sequence analysis of porcine deltacoronaviruses in southern China.
AB - BACKGROUND: Following the initial isolation of porcine deltacoronavirus (PDCoV)
from pigs with diarrheal disease in the United States in 2014, the virus has been
detected on swine farms in some provinces of China. To date, little is known
about the molecular epidemiology of PDCoV in southern China where major swine
production is operated. RESULTS: To investigate the prevalence of PDCoV in this
region and compare its activity to other enteric disease of swine caused by
porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis coronavirus
(TGEV), and porcine rotavirus group C (Rota C), 390 fecal samples were collected
from swine of various ages from 15 swine farms with reported diarrhea. Fecal
samples were tested by reverse transcription-PCR (RT-PCR) that targeted PDCoV,
PEDV, TGEV, and Rota C, respectively. PDCoV was detected exclusively from nursing
piglets with an overall prevalence of approximate 1.28 % (5/390), not in suckling
and fattening piglets. Interestingly, all of PDCoV-positive samples were from
2015 rather than 2012-2014. Despite a low detection rate, PDCoV emerged in each
province/region of southern China. In addition, compared to TGEV (1.54 %, 5/390)
or Rota C (1.28 %, 6/390), there were highly detection rates of PEDV (22.6 %,
88/390) in those samples. Notably, all five PDCoV-positive piglets were co
infected by PEDV. Furthermore, phylogenetic analysis of spike (S) and
nucleocapsid (N) gene sequences of PDCoVs revealed that currently circulating
PDCoVs in southern China were more closely related to other Chinese strains of
PDCoVs than to those reported in United States, South Korea and Thailand.
CONCLUSIONS: This study demonstrated that PDCoV was present in southern China
despite the low prevalence, and supported an evolutionary theory of geographical
clustering of PDCoVs.
PMID- 27496132
TI - Macular choroidal thickness in normal Egyptians measured by swept source optical
coherence tomography.
AB - BACKGROUND: To provide a normal database of choroidal thickness (CT) in nine
Early Treatment Diabetes Retinopathy Study (ETDRS) subfields in Egypt using deep
range imaging swept source optical coherence tomography (DRI SS OCT). METHODS:
This study included a total of 129 eyes of 71 normal Egyptian subjects,
comprising 63 males and 66 females. The mean age was 36.85 +/- 14.22 years
(range, 16-67 years). The mean axial length was 23.84 +/- 0.78 mm. CT was
measured in nine subfields as defined by the ETDRS-style grid using a DRI SS OCT,
and line measurements of subfoveal choroidal thicknesses (SFCT) were also
performed. RESULTS: Mean SFCT was 300.87 +/- 72.256 MUm for ring measurements and
319.72 +/- 76.45 MUm for line measurements (P = 0.04). CT was higher in the
superior and temporal quadrants than the inferior and nasal quadrants. A negative
correlation between subfoveal choroidal thickness and age was detected in all
regions (P < 0.001) except the nasal quadrant. A negative correlation between the
SFCT and axial length was also detected (P < 0.001). Males tended to have a
thicker choroid than females; however, the difference was not significant.
CONCLUSIONS: DRI SS OCT provides a topographic map of choroidal thickness with an
ETDRS layout. This study establishes, for the first time, a normal database for
CT in the Egyptian population. Age and axial length were associated with
choroidal parameters in healthy subjects. Line measurements of the SFCT differed
significantly from SFCT ring measurements, so it is recommended that each method
be compared independently.
PMID- 27496133
TI - Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of
SCLC Cell Lines In Vitro and In Vivo.
AB - Small-cell lung cancer (SCLC) cells have rapid proliferation, universal Rb
inactivation, and high rates of MYC family amplification, making aurora kinase
inhibition a natural target. Preclinical studies have demonstrated activity for
Aurora A and pan-Aurora inhibitors with some relationship to MYC family
expression. A clinical trial showed activity for an Aurora kinase A inhibitor,
but no biomarkers were evaluated. We screened a panel of 23 SCLC lines with and
without MYC family gene amplification or high MYC family gene expression for
growth inhibition by the highly potent, selective aurora kinase B inhibitor
barasertib. Nine of the SCLC lines were very sensitive to growth inhibition by
barasertib, with IC50 values of <50 nmol/L and >75% growth inhibition at 100
nmol/L. Growth inhibition correlated with cMYC amplification (P = 0.018) and cMYC
gene expression (P = 0.026). Sensitive cell lines were also enriched in a
published MYC gene signature (P = 0.042). In vivo, barasertib inhibited the
growth of xenografts established from an SCLC line that had high cMYC gene
expression, no cMYC amplification, and was positive for the core MYC gene
signature. Our studies suggest that SCLC tumors with cMYC amplification/high gene
expression will frequently respond to Aurora B inhibitors and that clinical
studies coupled with predictive biomarkers are indicated. Mol Cancer Ther;
15(10); 2314-22. (c)2016 AACR.
PMID- 27496134
TI - Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma.
AB - RET fusions have been found in lung adenocarcinoma, of which KIF5B-RET is the
most prevalent. We established inducible KIF5B-RET transgenic mice and KIF5B-RET
dependent cell lines for preclinical modeling of KIF5B-RET-associated lung
adenocarcinoma. Doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET transgenic mice
developed invasive lung adenocarcinoma with desmoplastic reaction. Tumors
regressed upon suppression of KIF5B-RET expression. By culturing KIF5B-RET
dependent BaF3 (B/KR) cells with increasing concentrations of cabozantinib or
vandetanib, we identified cabozantinib-resistant RETV804L mutation and vandetanib
resistant-RETG810A mutation. Among cabozantinib, lenvatinib, ponatinib, and
vandetanib, ponatinib was identified as the most potent inhibitor against KIF5B
RET and its drug-resistant mutants. Interestingly, the vandetanib-resistant KIF5B
RETG810A mutant displayed gain-of-sensitivity (GOS) to ponatinib and lenvatinib.
Treatment of doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice with
ponatinib effectively induced tumor regression. These results indicate that KIF5B
RET-associated lung tumors are addicted to the fusion oncogene and ponatinib is
the most effective inhibitor for targeting KIF5B-RET in lung adenocarcinoma.
Moreover, this study finds a novel vandetanib-resistant RETG810A mutation and
identifies lenvatinib and ponatinib as the secondary drugs to overcome this
vandetanib resistance mechanism. Mol Cancer Ther; 15(10); 2521-9. (c)2016 AACR.
PMID- 27496135
TI - Spectrum and Degree of CDK Drug Interactions Predicts Clinical Performance.
AB - Therapeutically targeting aberrant intracellular kinase signaling is attractive
from a biological perspective but drug development is often hindered by
toxicities and inadequate efficacy. Predicting drug behaviors using cellular and
animal models is confounded by redundant kinase activities, a lack of unique
substrates, and cell-specific signaling networks. Cyclin-dependent kinase (CDK)
drugs exemplify this phenomenon because they are reported to target common
processes yet have distinct clinical activities. Tumor cell studies of ATP
competitive CDK drugs (dinaciclib, AG-024322, abemaciclib, palbociclib,
ribociclib) indicate similar pharmacology while analyses in untransformed cells
illuminates significant differences. To resolve this apparent disconnect, drug
behaviors are described at the molecular level. Nonkinase binding studies and
kinome interaction analysis (recombinant and endogenous kinases) reveal that
proteins outside of the CDK family appear to have little role in
dinaciclib/palbociclib/ribociclib pharmacology, may contribute for abemaciclib,
and confounds AG-024322 analysis. CDK2 and CDK6 cocrystal structures with the
drugs identify the molecular interactions responsible for potency and kinase
selectivity. Efficient drug binding to the unique hinge architecture of CDKs
enables selectivity toward most of the human kinome. Selectivity between CDK
family members is achieved through interactions with nonconserved elements of the
ATP-binding pocket. Integrating clinical drug exposures into the analysis
predicts that both palbociclib and ribociclib are CDK4/6 inhibitors, abemaciclib
inhibits CDK4/6/9, and dinaciclib is a broad-spectrum CDK inhibitor
(CDK2/3/4/6/9). Understanding the molecular components of potency and selectivity
also facilitates rational design of future generations of kinase-directed drugs.
Mol Cancer Ther; 15(10); 2273-81. (c)2016 AACR.
PMID- 27496137
TI - Pharmacological Profile of BI 847325, an Orally Bioavailable, ATP-Competitive
Inhibitor of MEK and Aurora Kinases.
AB - Although the MAPK pathway is frequently deregulated in cancer, inhibitors
targeting RAF or MEK have so far shown clinical activity only in BRAF- and NRAS
mutant melanoma. Improvements in efficacy may be possible by combining inhibition
of mitogenic signal transduction with inhibition of cell-cycle progression. We
have studied the preclinical pharmacology of BI 847325, an ATP-competitive dual
inhibitor of MEK and Aurora kinases. Potent inhibition of MEK1/2 and Aurora A/B
kinases by BI 847325 was demonstrated in enzymatic and cellular assays.
Equipotent effects were observed in BRAF-mutant cells, whereas in KRAS-mutant
cells, MEK inhibition required higher concentrations than Aurora kinase
inhibition. Daily oral administration of BI 847325 at 10 mg/kg showed efficacy in
both BRAF- and KRAS-mutant xenograft models. Biomarker analysis suggested that
this effect was primarily due to inhibition of MEK in BRAF-mutant models but of
Aurora kinase in KRAS-mutant models. Inhibition of both MEK and Aurora kinase in
KRAS-mutant tumors was observed when BI 847325 was administered once weekly at 70
mg/kg. Our studies indicate that BI 847325 is effective in in vitro and in vivo
models of cancers with BRAF and KRAS mutation. These preclinical data are
discussed in the light of the results of a recently completed clinical phase I
trial assessing safety, tolerability, pharmacokinetics, and efficacy of BI 847325
in patients with cancer. Mol Cancer Ther; 15(10); 2388-98. (c)2016 AACR.
PMID- 27496136
TI - Single Agent and Synergistic Activity of the "First-in-Class" Dual PI3K/BRD4
Inhibitor SF1126 with Sorafenib in Hepatocellular Carcinoma.
AB - Deregulated PI3K/AKT/mTOR, Ras/Raf/MAPK, and c-Myc signaling pathways are of
prognostic significance in hepatocellular carcinoma (HCC). Sorafenib, the only
drug clinically approved for patients with advanced HCC, blocks the Ras/Raf/MAPK
pathway but it does not inhibit the PI3K/AKT/mTOR pathway or c-Myc activation.
Hence, there is an unmet medical need to identify potent PI3K/BRD4 inhibitors,
which can be used either alone or in combination with sorafenib to treat patients
with advanced HCC. Herein, we show that SF1126 (pan PI3K/BRD4 inhibitor) as
single agent or in combination with sorafenib inhibited proliferation, cell
cycle, apoptosis, and multiple key enzymes in PI3K/AKT/mTOR and Ras/Raf/MAPK
pathway in Hep3B, HepG2, SK-Hep1, and Huh7 HCC cell lines. We demonstrate that
the active moiety of the SF1126 prodrug LY294002 binds to and blocks BRD4
interaction with the acetylated histone-H4 chromatin mark protein and displaced
BRD4 coactivator protein from the transcriptional start site of MYC in Huh7 and
SK-Hep1 HCC cell lines. Moreover, SF1126 blocked expression levels of c-Myc in
HCC cells. Treatment of SF1126 either alone or in combination with sorafenib
showed significant antitumor activity in vivo Our results establish that SF1126
is a dual PI3K/BRD4 inhibitor. This agent has completed a phase I clinical trial
in humans with good safety profile. Our data support the potential future
consideration of a phase II clinical trial of SF1126, a clinically relevant dual
"first-in-class" PI3K/BRD4 inhibitor in advanced HCC, and a potential combination
with sorafenib. Mol Cancer Ther; 15(11); 2553-62. (c)2016 AACR.
PMID- 27496140
TI - The Impact of Community-Based Supports and Services on Quality of Life Among the
Elderly in China: A Longitudinal Study.
AB - Community-based supports and services (CBSS) have been developing rapidly in
China as a new way of satisfying the needs of elderly people. However, it is not
clear how pervasive these services are or whether the availability of CBSS
impacts quality of life. This study examines trends in CBSS and the impact of the
perceived CBSS availability on self-reported quality of life among the elderly in
China. We found a significant increase in perceived CBSS availability from 2005
to 2011, but the perceived availability of CBSS varies by the type of CBSS.
Multivariate analyses show that home medical visits (beta = .181, p = .03),
psychological support (beta = .332, p = .02), social and recreation activities
(beta = .231, p = .02), and legal consulting services (beta = .271, p = .02) were
each significantly associated with a good quality of life. Results from this
study provide insight that can inform CBSS strategies and the development of new
services for the elderly in China.
PMID- 27496138
TI - Alterative Expression and Localization of Profilin 1/VASPpS157 and Cofilin
1/VASPpS239 Regulates Metastatic Growth and Is Modified by DHA Supplementation.
AB - Profilin 1, cofilin 1, and vasodialator-stimulated phosphoprotein (VASP) are
actin-binding proteins (ABP) that regulate actin remodeling and facilitate cancer
cell metastases. miR-17-92 is highly expressed in metastatic tumors and profilin1
and cofilin1 are predicted targets. Docosahexaenoic acid (DHA) inhibits cancer
cell proliferation and adhesion. These studies tested the hypothesis that the
metastatic phenotype is driven by changes in ABPs including alternative
phosphorylation and/or changes in subcellular localization. In addition, we
tested the efficacy of DHA supplementation to attenuate or inhibit these changes.
Human lung cancer tissue sections were analyzed for F-actin content and
expression and cellular localization of profilin1, cofilin1, and VASP (S157 or
S239 phosphorylation). The metastatic phenotype was investigated in A549 and
MLE12 cells lines using 8 Br-cAMP as a metastasis inducer and DHA as a
therapeutic agent. Migration was assessed by wound assay and expression measured
by Western blot and confocal analysis. miR-17-92 expression was measured by qRT
PCR. Results indicated increased expression and altered cellular distribution of
profilin1/VASP(pS157), but no changes in cofilin1/VASP(pS239) in the human
malignant tissues compared with normal tissues. In A549 and MLE12 cells, the
expression patterns of profilin1/VASP(pS157) or cofilin1/VASP(pS239) suggested an
interaction in regulation of actin dynamics. Furthermore, DHA inhibited cancer
cell migration and viability, ABP expression and cellular localization, and
modulated expression of miR-17-92 in A549 cells with minimal effects in MLE12
cells. Further investigations are warranted to understand ABP interactions,
changes in cellular localization, regulation by miR-17-92, and DHA as a novel
therapeutic. Mol Cancer Ther; 15(9); 2220-31. (c)2016 AACR.
PMID- 27496139
TI - Pre-pregnancy obesity and non-adherence to multivitamin use: findings from the
National Pregnancy Risk Assessment Monitoring System (2009-2011).
AB - BACKGROUND: Although adequate folic acid or multivitamins can prevent up to 70 %
of neural tube defects, the majority of U.S. non-pregnant women of childbearing
age do not use multivitamins every day. Factors influencing consistent
multivitamin use are not fully explored. This study aims to investigate the
association between pre-pregnancy body mass index (BMI) and multivitamin use
before pregnancy using a large, nationally representative sample of women with
recent live births. METHODS: The national 2009-2011 Pregnancy Risk Assessment
Monitoring System data were analyzed. The sample included women with recent
singleton live births (N = 104,211). The outcome of interest was multivitamin use
which was categorized as no multivitamin use, 1-3 times/week, 4-6 times/week, and
daily use. Maternal BMI was examined as underweight (<18.50 kg/m(2)), normal
weight (18.50-24.99 kg/m(2)), overweight (25.00-29.99 kg/m(2)), and obese
(>=30.00 kg/m(2)). Multinomial logistic regression was conducted, and adjusted
odds ratios and 95 % confidence intervals were calculated. RESULTS: Compared to
women with normal weight, overweight and obese women had significantly increased
odds of not taking multivitamins after adjusting for confounding factors.
Further, the lack of multivitamin use increased in magnitude with the level of
BMI (ORoverweight = 1.2, 95 % CI = 1.1-1.3; ORobese = 1.4, 95 % CI = 1.2-1.5).
CONCLUSIONS: Obese and overweight women were less likely to follow the
recommendation for preconception multivitamin use compared to normal weight
women. All health care professionals must enhance preconception care with
particular attention to overweight and obese women. Preconception counseling may
be an opportunity to discuss healthy eating and benefits of daily multivitamin
intake before pregnancy.
PMID- 27496141
TI - Involving Caregivers of People With Dementia to Validate Booklets on Food-Related
Activities: A Qualitative Think-Aloud Study.
AB - This study is the first to explore informal dementia caregivers' perceptions and
outlook on written materials about all food-related processes: shopping, food
preparation, and eating. The aim of the study was to develop and evaluate the
content, format, and usefulness of two separate booklets (one newly developed and
one existing) on food-related processes. Twenty dementia caregivers were provided
with one of the two booklets, and a Think-Aloud method was used to gather
information about their views on the booklets. The findings indicated that
incorporating all three food processes in a new booklet could be beneficial for
the participant. Shopping, purchasing food, driving, and dangers in the kitchen
were addressed only in the developed booklet, and participants regarded them as
important and useful areas to address. Therefore, this study has shown that
tailored information may enhance caregivers' confidence and support them in
making decisions to help them adapt to food-related changes.
PMID- 27496142
TI - The effect of age on relational encoding as revealed by hippocampal functional
connectivity.
AB - The neural processes mediating cognition occur in networks distributed throughout
the brain. The encoding and retrieval of relational memories, memories for
multiple items or multifeatural events, is supported by a network of brain
regions, particularly the hippocampus. The hippocampal coupling hypothesis
suggests that the hippocampus is functionally connected with the default mode
network (DMN) during retrieval, but during encoding, decouples from the DMN.
Based on prior research suggesting that older adults are less able to modulate
between brain network states, we tested the hypothesis that older adults'
hippocampus would show functional connectivity with the DMN during relational
encoding. The results suggest that, while the hippocampus is functionally
connected to some regions of the DMN during relational encoding in both younger
and older adults, older adults show additional DMN connectivity. Such age-related
changes in network modulation appear not to be mediated by compensatory
processes, but rather to reflect a form of neural inefficiency, most likely due
to reduced inhibition.
PMID- 27496143
TI - A decade of intestinal protozoan epidemiology among settled immigrants in Qatar.
AB - BACKGROUND: The World Health Organization estimates that about 3.5 billion people
worldwide are affected by intestinal parasitic infections. Reports have already
emphasized the role of immigrants in outbreaks of parasitic diseases in
industrialized countries. With the mass influx of immigrants to Qatar, patent
intestinal parasitic infections have been observed. Herein, the prevalence of
intestinal protozoan infections was analysed in 29,286 records of subjects
referred for stool examination at the Hamad Medical Corporation over the course
of a decade (2005 to 2014, inclusive). RESULTS: Overall prevalence of combined
protozoan infections was 5.93 % but there were significant temporal trends, age
and sex effects and those arising from the region of origin of the subjects. The
most common protozoan was Blastocystis hominis (overall prevalence 3.45 %).
Giardia duodenalis, Chilomastix mesnili, Entamoeba coli, Entamoeba hartmanni,
Endolimax nana, Iodamoeba butschlii, Entamoeba histolytica/dispar,
Cryptosporidium sp. and a single case of Isospora were also detected. The
prevalence of combined protozoan infections, G. duodenalis and the non-pathogenic
amoebae all declined significantly across the decade. That of B. hominis varied
between years but showed no directional trend across years and there was no
evidence that prevalence of E. histolyitica/dispar changed significantly.
Protozoan infections were observed among all regional groups, but prevalence was
higher among subjects from the Arabian Peninsula, Africa and Asia compared to
those from the Eastern Mediterranean and Qatar. Prevalence was higher among male
subjects in all cases, but age-prevalence profiles differed between the taxa.
CONCLUSION: These results offer optimism that prevalence will continue to decline
in the years ahead.
PMID- 27496144
TI - How old are you, really? Communicating chronic risk through 'effective age' of
your body and organs.
AB - In communicating chronic risks, there is increasing use of a metaphor that can be
termed 'effective-age': the age of a 'healthy' person who has the same risk
profile as the individual in question. Popular measures include 'real-age',
'heart-age', 'lung-age' and so on.Here we formally define this concept, and
illustrate its use in a variety of areas. We explore conditions under which the
years lost or gained that are associated with exposure to risk factors depends
neither on current chronological age, nor the period over which the risk is
defined. These conditions generally hold for all-cause adult mortality, which
enables a simple and vivid translation from hazard-ratios to years lost or gained
off chronological age. Finally we consider the attractiveness and impact of this
concept.Under reasonable assumptions, the risks associated with specific
behaviours can be expressed in terms of years gained or lost off your effective
age. The idea of effective age appears a useful and attractive metaphor to
vividly communicate risks to individuals.
PMID- 27496145
TI - Capsule Commentary on Bodenmann et al., Case Management May Reduce Emergency
Department Frequent Use in a Universal Health Coverage System: a Randomized
Controlled Trial.
PMID- 27496146
TI - Early severe anemia as the first sign of cystic fibrosis.
AB - Severe anemia is reported to occur rarely in patients with cystic fibrosis (CF).
This study aimed to determine the factors associated with early severe anemia in
infants with CF. This study included 231 infants with CF from 3 pediatric CF
centers ten year period that were retrospectively reviewed in terms of severe
anemia as the first sign of CF. Factors that could affect anemia, such as age,
pancreatic insufficiency, mutations, vitamin A and E, and albumin level were
evaluated. Clinical and laboratory findings in CF patients that presented with
severe anemia and no respiratory symptoms were compared to those in CF patients
that did not present with severe anemia. Severe anemia as the first sign of CF
was noted in 17 of 231 patients. Patient age, prolonged PT/INR and the albumin
level differed significantly between the 2 groups of patients (P < 0.001).
Feeding pattern, pancreatic insufficiency, vitamin E and A levels, and the types
of genetic mutations did not differ between the 2 groups. The mean hemoglobin
level was 5.59 +/- 0.21 g/dL and respiratory symptoms began a mean 6.3 months
after diagnosis of CF in the anemia group. CONCLUSION: In early infancy severe
anemia in the absence of respiratory symptoms can be the first sign of CF. CF
should be considered in the differential diagnosis of severe anemia in infants.
Anemia can occur several months before respiratory symptoms in patients with CF
and may be caused due to several reasons. WHAT IS KNOWN: * Severe anemia as a
first sign is reported to occur rarely in patients with cystic fibrosis. *
Although anemia is well known in cystic fibrosis, factors that cause severe
anemia are not known clearly. What is New: * This study shows the importance of
severe anemia as the first sign of cystic fibrosis. * Anemia can occur several
months before respiratory symptoms in patients with CF.
PMID- 27496147
TI - Phenylketonuria screening in the Republic of Macedonia.
AB - Phenylketonuria is an autosomal recessive inborn error of metabolism which can be
prevented by early and continuous treatment. Therefore newborn screening for
phenylketonuria has been introduced in many countries. We present here the
results of the selective newborn screening for inborn errors of metabolism,
including PKU, performed by tandem mass spectrometry which has been introduced in
Macedonia since 2011.
PMID- 27496148
TI - Cumulative risk of false positive test in relation to breast symptoms in
mammography screening: a historical prospective cohort study.
AB - Mammography has been found effective as the primary screening test for breast
cancer. We estimated the cumulative probability of false positive screening test
results with respect to symptom history reported at screen. A historical
prospective cohort study was done using individual screening data from 413,611
women aged 50-69 years with 2,627,256 invitations for mammography screening
between 1992 and 2012 in Finland. Symptoms (lump, retraction, and secretion) were
reported at 56,805 visits, and 48,873 visits resulted in a false positive
mammography result. Generalized linear models were used to estimate the
probability of at least one false positive test and true positive at screening
visits. The estimates were compared among women with and without symptoms
history. The estimated cumulative probabilities were 18 and 6 % for false
positive and true positive results, respectively. In women with a history of a
lump, the cumulative probabilities of false positive test and true positive were
45 and 16 %, respectively, compared to 17 and 5 % with no reported lump. In women
with a history of any given symptom, the cumulative probabilities of false
positive test and true positive were 38 and 13 %, respectively. Likewise, women
with a history of a 'lump and retraction' had the cumulative false positive
probability of 56 %. The study showed higher cumulative risk of false positive
tests and more cancers detected in women who reported symptoms compared to women
who did not report symptoms at screen. The risk varies substantially, depending
on symptom types and characteristics. Information on breast symptoms influences
the balance of absolute benefits and harms of screening.
PMID- 27496149
TI - Randomised, waiting list controlled trial of cognitive-behavioural therapy for
persistent postconcussional symptoms after predominantly mild-moderate traumatic
brain injury.
AB - BACKGROUND: Persistent postconcussional symptoms (PCS) can be a source of
distress and disability following traumatic brain injury (TBI). Such symptoms
have been viewed as difficult to treat but may be amenable to psychological
approaches such as cognitive-behavioural therapy (CBT). OBJECTIVES: To evaluate
the effectiveness of a 12-session individualised, formulation-based CBT
programme. METHOD: Two-centre randomised waiting list controlled trial with 46
adults with persistent PCS after predominantly mild-to-moderate TBI (52% with
post-traumatic amnesia (PTA)<=24 hours), but including some with severe TBIs (20%
with PTA>7 days). RESULTS: Improvements associated with CBT were found on the
primary outcome measures relating to quality of life (using the Quality of Life
Assessment Schedule and the Brain Injury Community Rehabilitation Outcome Scale).
Treatment effects after covarying for treatment duration were also found for PCS
and several secondary outcomes, including measures of anxiety and fatigue (but
not depression or post-traumatic stress disorder (PTSD)). Improvements were more
apparent for those completing CBT sessions over a shorter period of time, but
were unrelated to medicolegal status, injury severity or length of time since
injury. CONCLUSIONS: This study suggests that CBT can improve quality of life for
adults with persistent PCS and potentially reduce symptoms for some, in the
context of outpatient brain injury rehabilitation services. TRIAL REGISTRATION
NUMBER: ISRCTN49540320.
PMID- 27496150
TI - Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis,
oxidative stress and pro-inflammatory cytokine expression in vivo.
AB - BACKGROUND: Complications of diabetes mellitus (DM) are related not only to
elevated plasma glucose, but also plasma glucose fluctuations. However, the
specific mechanism underlying the role of plasma glucose fluctuation in the
pathogenesis of DM complications remains poorly understood. In the present study,
the influence of acute fluctuant hyperglycemia and persistent hyperglycemia on
vascular endothelial cell apoptosis, function, oxidative stress and inflammation
was examined in vivo. METHODS: Rats were assigned to three different groups (n =
10/group) that received 48-h infusions of saline (SAL group), continuous 50 %
glucose (constant high glucose group [CHG]), or intermittent 50 % glucose (acute
blood glucose fluctuation group [AFG]). Plasma 8-isoprostaglandin, interleukin-6
(IL-6), tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion
molecule-1 (ICAM-1) levels were quantified by using enzyme-linked immunosorbent
assay (ELISA) commercial kits. Plasma insulin levels were measured by
radioimmunoassays (RIAs) using kits. The aortic segment was collected. The levels
of malondialdehyde (MDA) and activity of glutathione peroxidase (GSH-PX) were
measured in endothelial homogenates prepared from endothelial cells harvested
from the aorta using colorimetric kits. Apoptosis of vascular endothelial cells
was determined with terminal deoxynucleotidyl transferase dUTP nick end labeling
(TUNEL). Endothelial dysfunction was assessed by isometric tension recording to
evaluate the endothelial function. The expression of B cell lymphoma-2 (Bcl-2),
Bcl-2 Associated X protein (Bax), pro caspase-3, caspase-3 p17, 3-nitrotyrosine
(3-NT) and p47phox protein in rat aortic endothelial cells were tested with
Western blot analysis. Endothelial cells reactive oxygen species (ROS) formation
was determined using dihydroethidium-dependent fluorescence microtopography in
aortic cryo-sections. Expression of IL-6, TNF-alpha and ICAM-1 mRNAs in vascular
endothelial cells were determined by real-time quantitative PCR. RESULTS:
Endothelial cells apoptosis and dysfunction were observed significantly in the
aortas of the AFG group (P < 0.05). The AFG had reduced Bcl-2 and pro caspase-3
levels and enhanced Bax mitochondrial translocation and caspase-3 p17 protein
levels in comparison with the CHG group (P < 0.05). Both AFG and CHG induced beta
cell dysfunction and insulin resistance (P < 0.05). AFG increased MDA and 8
isoprostaglandin levels in plasma, oxidative stress in vascular endothelial
cells, and inflammatory cytokines in plasma and vascular endothelial cells (P <
0.05). CONCLUSION: Acute glucose fluctuation may cause significant oxidative
stress and inflammation in endothelial cells, increase the adhesion of monocytes
to endothelial cells, and elevate endothelial cell apoptosis, resulting in severe
cardiovascular injury.
PMID- 27496151
TI - Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st
century. A prospective multicenter study.
AB - The aim of this multicenter study was to assess the present risk of fetal
complications and the inherent risk factors in pregnant women with lupus
nephritis. Seventy-one pregnancies in 61women (59 Caucasians and 2 Asians) with
lupus nephritis were prospectively followed between October 2006 and December
2013. All patients received a counselling visit within 3 months before the
beginning of pregnancy and were followed by a multidisciplinary team. At baseline
mild active nephritis was present in 15 cases (21.1%). Six pregnancies (8.4%)
resulted in fetal loss. Arterial hypertension at baseline (P = 0.003), positivity
for lupus anticoagulant (P = 0.001), anticardiolipin IgG antibodies (P = 0.007),
antibeta2 IgG (P = 0.018) and the triple positivity for antiphospholipid
antibodies (P = 0.004) predicted fetal loss. Twenty pregnancies (28.2%) ended pre
term and 12 newborns (16.4%) were small for gestational age. Among the
characteristics at baseline, high SLE disease activity index (SLEDAI) score (P =
0.027), proteinuria (P = 0.045), history of renal flares (P = 0.004), arterial
hypertension (P = 0.009) and active lupus nephritis (P = 0.000) increased the
probability of preterm delivery. Odds for preterm delivery increased by 60% for
each quarterly unit increase in SLEDAI and by 15% for each quarterly increase in
proteinuria by 1 g per day. The probability of having a small for gestational age
baby was reduced by 85% in women who received hydroxychloroquine therapy (P =
0.023). In this study, the rate of fetal loss was low and mainly associated with
the presence of antiphospholipid antibodies. Preterm delivery remains a frequent
complication of pregnancies in lupus. SLE and lupus nephritis activity are the
main risk factors for premature birth. Arterial hypertension predicted both fetal
loss and preterm delivery. Based on our results the key for a successful
pregnancy in lupus nephritis is a multidisciplinary approach with close medical,
obstetric and neonatal monitoring. This entails: a) a preconception evaluation to
establish and inform women about pregnancy risks; b) planning pregnancy during
inactive lupus nephritis, maintained inactive with the lowest possible dosage of
allowed drugs; c) adequate treatment of known risk factors (arterial
hypertension, antiphospholipid and antibodies); d) close monitoring during and
after pregnancy to rapidly identify and treat SLE flares and obstetric
complications.
PMID- 27496152
TI - Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine
the Holy Grail we are looking for?
AB - Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid
syndrome (APS), with an important social and economical cost. Antiplatelet and
anticoagulant agents are effective in preventing the clinical manifestations in
the majority of the patients. However, a consistent proportion of the pregnant
women present recurrences in spite of the standard therapy. Observational studies
and anecdotal reports raised the issue of additional therapeutic strategies in
these refractory cases. Among these, anti-malarials (AMs) and in particular
hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in
other systemic autoimmune rheumatic conditions. AMs display a pleiotropic
activity spanning from immunomodulation effect to anti-inflammatory and anti
thrombotic activities, all of which potentially useful in APS. The well-known
safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune
rheumatic disorders including APS and observational reports suggested a
protective effect on obstetrical recurrences. Since thrombosis does not seem to
be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment
with HCQ should be related to other pharmacological effects rather than to the
anti-platelet or anti-thrombotic activity of the molecule. Experimental models
showed that HCQ may restore some defective biological functions induced by anti
phospholipid antibodies (aPL) on trophoblasts and a recent study reported a
protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental
abnormalities. Although the rational behind the use of HCQ in obstetric APS is
sound, the evidence from the real life is not conclusive and a critical appraisal
through clinical trials is mandatory.
PMID- 27496153
TI - The 2014 primary health care reform in Poland: Short-term fixes instead of a long
term strategy.
AB - At the end of 2013, the Minister of Health started legislative changes directly
and indirectly affecting primary health care (PHC). The reforms were widely
criticised among certain groups of medical professionals, including family
medicine physicians. The latter mainly criticised the formal inclusion of
specialists in internal diseases and paediatrics into PHC within the statutory
health care system, which in practice meant that these two groups of specialists
were no longer required to specialize in family medicine from 2017 in order to
enter into contracts with the public payer and would be able to set up solo PHC
practices-something over which family medicine physicians used to have a
monopoly. They argued that paediatricians and internists did not have the
necessary professional competencies to work as PHC physicians and thus assure
provision of a comprehensive and coordinated PHC. The government's stance was
that the proposed measure was necessary to assure the future provision of PHC,
given the shortage of specialists in family medicine. Certain groups of medical
professionals were also supportive of the proposed change. The key argument in
favour was that it could improve access to PHC, especially for children. However,
while this was not the subject of the critique or even a policy debate, the
proposal ignored the increasing health care needs of older patients-the key
recipients of PHC services. The policy was passed in the Parliament in March
April 2014 without a dialogue with the key stakeholders, which is typical of
health care (and other) reforms in Poland. The strong opposition against the
reform from the family medicine specialists, represented by two strong
organisations, may jeopardise the policy implementation in the future.
PMID- 27496154
TI - Physician density planning in a public healthcare system: Complexities, threats
and opportunities-The case of the Israeli healthcare system.
AB - Human-resource planning in healthcare is one of the most significant challenges
that healthcare systems worldwide face. Among all healthcare professions, the
planning of physician supply is the most complex of all due to physicians'
lengthy training and many specialties. Forecasts showing a disturbing downward
trend in the ratio of physicians to population in Israel prompted the Israeli
Government in 2010 to establish a committee mandated to predict demand for
physicians and recommend steps to adjust supply to it. The committee analyzed
numerous variables that affect physician supply and demand and recommended
measures that in greater part were implemented. The article discusses the
methodology of the committee, its recommendations, and their implementation such
as a 52% increase in the number of first-year medical students between 2010 and
2012. Its analysis of the current situation shows that the implementation of the
recommendations successfully stemmed the decrease in physician density and
attained the committee's other long-term objectives: physician density of 2.9 per
1000 of population and an increase (32.5%) in the number of physicians who began
training in targeted specialties.
PMID- 27496155
TI - What drives public health care expenditure growth? Evidence from Swiss cantons,
1970-2012.
AB - A better understanding of the determinants of public health care expenditures is
key to designing effective health policies. We integrate demand and supply-side
determinants and factors from political economy into an empirical analysis of the
highly decentralized Swiss health care system and control for major health care
finance reforms. We compile a novel data set of the cantonal health care
expenditure in Switzerland, which currently amounts to about one fifth of total
health care expenditure. We analyze the period 1970-2012 and use dynamic panel
estimation methods. We find that per capita income, the unemployment rate and the
share of foreigners are positively related to public health care expenditure
growth. With regard to political economy aspects, public health care expenditures
increase with the share of women elected to parliament. However, institutional
restrictions for politicians, such as fiscal rules, do not appear to limit public
health care expenditure growth.
PMID- 27496156
TI - Introducing Diagnosis-Related Groups in Kazakhstan: Evolution, achievements, and
challenges.
AB - In 2012, Kazakhstan introduced Diagnosis-Related Groups (DRGs), as part of a
package of reforms which sought to contain costs and to improve efficiency and
transparency in the health system; but the main challenge was to design and
implement a DRG system in just one year. In 2011-2012, Kazakhstan developed its
own DRG system. Initially 180 DRGs were defined to group inpatient cases but this
number was subsequently expanded to more than 400. Because of time limits, the
cost weights had to be derived in the absence of existing standard hospital cost
accounting systems, and a national patient data transfer system also needed
developing. Most importantly, huge efforts were needed to develop a regulatory
framework and build up DRG capabilities at a national level. The implementation
of DRGs was facilitated by strong political will for their introduction as part
of a coherent package of health reforms, and consolidated efforts to build
capacity. DRGs are now the key payment mechanism for hospitals. However the
reforms are not fully institutionalized: the DRG structure is continuously being
refined in a context of data limitations, and the revision of cost weights is
most affected by insufficient data and the lack of standardized reporting
mechanisms. Capacity around DRG coding is also still being developed. Countries
planning to introduce DRG systems should be aware of the challenges in moving too
quickly to implement DRGs as the main hospital reimbursement mechanism.
PMID- 27496157
TI - Learning game for training child bicyclists' situation awareness.
AB - Encouraging more children to bicycle would produce both environmental and health
benefits, but bicycling accidents are a major source of injuries and fatalities
among children. One reason for this may be children's less developed hazard
perception skills. We assume that children's situation awareness could be trained
with a computer based learning game, which should also improve their hazard
perception skills. In this paper, we present a prototype for such a game and
pilot it with 8-9year old children. The game consisted of videos filmed from a
bicyclist's perspective. Using a touchscreen, the player's task was to point out
targets early enough to gain points. The targets were either overt (other visible
road users on a potentially conflicting course) or covert (occlusions, i.e.
locations where other road users could suddenly emerge). If a target was missed
or identified too late, the video was paused and feedback was given. The game was
tested with 49 children from the 2nd grade of primary school (aged 8-9). 31 young
adults (aged 22-34) played the game for comparison. The effect of the game on
situation awareness was assessed with situation awareness tests in a crossover
design. Similar videos were used in the tests as in the game, but instead of
pointing out the targets while watching, the video was suddenly masked and
participants were asked to locate all targets which had been present just before
the masking, choosing among several possible locations. Their performance was
analyzed using Signal Detection Theory and answer latencies. The game decreased
answer latency and marginally changed response bias in a less conservative
direction for both children and adults, but it did not significantly increase
sensitivity for targets. Adults performed better in the tests and in the game,
and it was possible to satisfactorily predict group membership based on the
scores. Children found it especially difficult to find covert targets. Overall,
the described version of the learning game cannot be regarded as an effective
tool for situation awareness/hazard perception training, but ways to improve the
game are discussed.
PMID- 27496158
TI - Attenuation and quantitation of virulence gene expression in quorum-quenched
Dickeya chrysanthemi.
AB - N-Acyl-homoserine lactones (AHLs)-dependent quorum sensing (QS) system(s) is
recruited by the soft rot bacterium Dickeya chrysanthemi for coordinating its
social activities such as secretion of plant cell wall-degrading enzymes, while
the main signal molecule and quantity dependence of virulence to QS in this
bacterium have not been clarified. To do this end, the involvement of AHLs in
African violet leaves and potato tuber maceration; swarming motility; pectate
lyase and polygalacturonase enzymes production and in planta expression of
virulence genes including pelE, pehX and pemA by electroporating two quorum
quenching vectors. The expression of two types of AHL-lactonase expressing vector
caused dramatic decrease in swarming motility, production of pectinolytic enzymes
and macerating of plant tissues. The maximum ability of quenching of QS in
repression of D. chrysanthemi virulence was assessed quantitatively by q-RT-PCR,
as expression of pelE, pehX and pemA genes were decreased 90.5-92.18 % in
quenched cells. We also showed that virulence and pathogenicity of this bacterium
was under the control of DHL-dependent QS system and that the existence of second
DHL operating system is probable for this bacterium. Thus, this signal molecule
would be the key point for future research to design DHL-specific lactonase
enzymes using bioinformatics methods.
PMID- 27496159
TI - Critical contribution of KV1 channels to the regulation of coronary blood flow.
AB - Ion channels in smooth muscle control coronary vascular tone, but the identity of
the potassium channels involved requires further investigation. The purpose of
this study was to evaluate the functional role of KV1 channels on porcine
coronary blood flow using the selective antagonist correolide. KV1 channel gene
transcripts were found in porcine coronary arteries, with KCNA5 (encoding KV1.5)
being most abundant (P < 0.001). Immunohistochemical staining demonstrated KV1.5
protein in the vascular smooth muscle layer of both porcine and human coronary
arteries, including microvessels. Whole-cell patch-clamp experiments demonstrated
significant correolide-sensitive (1-10 uM) current in coronary smooth muscle. In
vivo studies included direct intracoronary infusion of vehicle or correolide into
a pressure-clamped left anterior descending artery of healthy swine (n = 5 in
each group) with simultaneous measurement of coronary blood flow. Intracoronary
correolide (~0.3-3 uM targeted plasma concentration) had no effect on heart rate
or systemic pressure, but reduced coronary blood flow in a dose-dependent manner
(P < 0.05). Dobutamine (0.3-10 ug/kg/min) elicited coronary metabolic
vasodilation and intracoronary correolide (3 uM) significantly reduced coronary
blood flow at any given level of myocardial oxygen consumption (P < 0.001).
Coronary artery occlusions (15 s) elicited reactive hyperemia and correolide (3
uM) reduced the flow volume repayment by approximately 30 % (P < 0.05). Taken
together, these data support a major role for KV1 channels in modulating baseline
coronary vascular tone and, perhaps, vasodilation in response to increased
metabolism and transient ischemia.
PMID- 27496160
TI - Recommendations for authors of manuscripts reporting inhibitor cases developed in
previously treated patients with hemophilia: communication from the SSC of the
ISTH.
AB - Aim The scope of this recommendation is to provide guidance for reporting of
inhibitor cases in previously treated patients (PTPs) with hemophilia A. This
guidance is intended to improve transparency and completeness of reporting of
observed events; it does not cover planning, executing or analyzing original
studies aimed at the assessment of inhibitor rates. Recommendation We recommend
that for each case of inhibitor development reported in a published paper, a
paragraph or a table is included in the main publication reporting as a minimum
the underlined data fields in Table . We recommend transparent reporting when any
of the suggested information is not available. We recommend that particular care
is used in reporting the timeline of events by clearly identifying a reference
time-point. We suggest that journals in the field adopt this guidance as
instructions for the authors and as a guide for reviewers. Conclusion Development
of inhibitors in PTPs is a very rare event. Standardized reporting of inhibitor
characteristics will contribute to generating a body of evidence otherwise not
available. Case by case reporting of the recommended data elements may shed light
on the natural history and risk factors of inhibitor development in PTPs and be
useful for tailoring care in similar future cases.
PMID- 27496162
TI - Support for indoor tanning policies among young adult women who indoor tan.
AB - The purpose of this study to examine support for indoor tanning policies and
correlates of policy support among young adult women who indoor tan. Non-Hispanic
white women ages 18-30 who indoor tanned in the past year (n = 356, M 23.3 age,
SD 3.1) recruited in the Washington, DC area from 2013 to 2016 completed measures
of indoor tanning behaviors, attitudes, perceptions, beliefs, and policy support.
Most women in the sample supported policies to prevent children under the age of
18 from indoor tanning (74.0 %) and stronger warnings about the risks of indoor
tanning on tanning devices (77.6 %); only 10.1 % supported a total ban. In
multivariable analyses, support for individual indoor tanning policies varied by
demographics (e.g., age), frequent indoor tanning behavior, indoor tanning
beliefs, and risk perceptions. Non-Hispanic white young adult women who indoor
tan, the primary consumers of indoor tanning, and a high-risk population, largely
support indoor tanning prevention policies implemented by many state governments
and those currently under review for national enactment. Given low levels of
support for a total indoor tanning ban, support for other potential policies
(e.g., increasing the minimum age to 21) should be investigated to inform future
steps to reduce indoor tanning and the associated health risks.
PMID- 27496163
TI - PHE guidance does warn about PSA testing.
PMID- 27496161
TI - The relative contribution of climate variability and vector control coverage to
changes in malaria parasite prevalence in Zambia 2006-2012.
AB - BACKGROUND: Four malaria indicator surveys (MIS) were conducted in Zambia between
2006 and 2012 to evaluate malaria control scale-up. Nationally, coverage of
insecticide-treated nets (ITNs) and indoor residual spraying (IRS) increased over
this period, while parasite prevalence in children 1-59 months decreased
dramatically between 2006 and 2008, but then increased from 2008 to 2010. We
assessed the relative effects of vector control coverage and climate variability
on malaria parasite prevalence over this period. METHODS: Nationally
representative MISs were conducted in April-June of 2006, 2008, 2010 and 2012 to
collect household-level information on malaria control interventions such as IRS,
ITN ownership and use, and child parasite prevalence by microscopic examination
of blood smears. We fitted Bayesian geostatistical models to assess the
association between IRS and ITN coverage and climate variability and malaria
parasite prevalence. We created predictions of the spatial distribution of
malaria prevalence at each time point and compared results of varying IRS, ITN,
and climate inputs to assess their relative contributions to changes in
prevalence. RESULTS: Nationally, the proportion of households owning an ITN
increased from 37.8 % in 2006 to 64.3 % in 2010 and 68.1 % in 2012, with
substantial heterogeneity sub-nationally. The population-adjusted predicted child
malaria parasite prevalence decreased from 19.6 % in 2006 to 10.4 % in 2008, but
rose to 15.3 % in 2010 and 13.5 % in 2012. We estimated that the majority of this
prevalence increase at the national level between 2008 and 2010 was due to
climate effects on transmission, although there was substantial heterogeneity at
the provincial level in the relative contribution of changing climate and ITN
availability. We predict that if climate factors preceding the 2010 survey were
the same as in 2008, the population-adjusted prevalence would have fallen to 9.9
% nationally. CONCLUSIONS: These results suggest that a combination of climate
factors and reduced intervention coverage in parts of the country contributed to
both the reduction and rebound in malaria parasite prevalence. Unusual rainfall
patterns, perhaps related to moderate El Nino conditions, may have contributed to
this variation. Zambia has demonstrated considerable success in scaling up vector
control. This analysis highlights the importance of accounting for climate
variability when using cross-sectional data for evaluation of malaria control
efforts.
PMID- 27496164
TI - Stress and Coping Predicts Adjustment and Glycemic Control in Adolescents with
Type 1 Diabetes.
AB - BACKGROUND: Adolescents with type 1 diabetes are at increased risk for
deteriorating glycemic control, poor quality of life, and depressive symptoms.
Stress and coping are related to these outcomes in adolescents with diabetes, yet
few studies have examined these constructs longitudinally. PURPOSE: This study
aimed to describe stress and coping in adolescents with type 1 diabetes and to
examine coping strategies as predictors of adolescent adjustment (i.e.,
depressive symptoms, quality of life) and glycemic control. METHODS: Adolescents
with type 1 diabetes completed measures of diabetes-related stress, coping,
symptoms of depression, and quality of life at baseline, 6 months, and 12 months.
Data on glycemic control were collected from the adolescents' medical charts.
RESULTS: The adolescents' use of primary control coping (e.g., problem solving)
and secondary control engagement coping (e.g., positive thinking) strategies
predicted significantly fewer problems with quality of life and fewer depressive
symptoms over time. In contrast, the use of disengagement coping strategies
(e.g., avoidance) predicted more problems with quality of life and depressive
symptoms. Coping was not a significant predictor of glycemic control. Coping
mediated the effects of diabetes-related stress on depressive symptoms and
quality of life. CONCLUSIONS: The ways in which adolescents with type 1 diabetes
cope with diabetes-related stress predict quality of life and symptoms of
depression but not glycemic control. Through the use of screening to identify
adolescent's diabetes-related stress and targeted interventions to improve coping
strategies, there is potential to improve outcomes.
PMID- 27496165
TI - What is the role of radiological testing of lower esophageal sphincter function?
AB - Radiological fluoroscopic evaluation remains the primary imaging modality of
choice to evaluate patients with swallowing disorders, despite the increasing
availability and technical advantages of nonradiological techniques and the
current radiological focus on cross-sectional imaging studies, such as computed
tomography and magnetic resonance imaging. The radiological swallowing evaluation
should be tailored to assess the entire upper gastrointestinal tract, including
the lower esophageal sphincter. Fluoroscopy enables the simultaneous assessment
of esophageal motility disorders, as well as structural pathologies, including
strictures, webs, rings, diverticula, and tumors. Mono- and double-contrast
esophagrams and solid bolus tests together allow assessment of lower esophageal
sphincter function and complement other methods, such as endoscopy, manometry, or
impedance planimetry. Here we review the role of radiological studies for correct
assessment of structural and functional pathologies at the level of the lower
esophageal sphincter.
PMID- 27496167
TI - Standardization of Arterial Stiffness Measurements Make Them Ready for Use in
Clinical Practice.
PMID- 27496166
TI - The genome-wide role of HSF-1 in the regulation of gene expression in
Caenorhabditis elegans.
AB - BACKGROUND: The heat shock response, induced by cytoplasmic proteotoxic stress,
is one of the most highly conserved transcriptional responses. This response,
driven by the heat shock transcription factor HSF1, restores proteostasis through
the induction of molecular chaperones and other genes. In addition to stress
dependent functions, HSF1 has also been implicated in various stress-independent
functions. In C. elegans, the HSF1 homolog HSF-1 is an essential protein that is
required to mount a stress-dependent response, as well as to coordinate various
stress-independent processes including development, metabolism, and the
regulation of lifespan. In this work, we have performed RNA-sequencing for C.
elegans cultured in the presence and absence of hsf-1 RNAi followed by treatment
with or without heat shock. This experimental design thus allows for the
determination of both heat shock-dependent and -independent biological targets of
HSF-1 on a genome-wide level. RESULTS: Our results confirm that C. elegans HSF-1
can regulate gene expression in both a stress-dependent and -independent fashion.
Almost all genes regulated by HS require HSF-1, reinforcing the central role of
this transcription factor in the response to heat stress. As expected, major
categories of HSF-1-regulated genes include cytoprotection, development,
metabolism, and aging. Within both the heat stress-dependent and -independent
gene groups, significant numbers of genes are upregulated as well as
downregulated, demonstrating that HSF-1 can both activate and repress gene
expression either directly or indirectly. Surprisingly, the cellular process most
highly regulated by HSF-1, both with and without heat stress, is cuticle
structure. Via network analyses, we identify a nuclear hormone receptor as a
common link between genes that are regulated by HSF-1 in a HS-dependent manner,
and an epidermal growth factor receptor as a common link between genes that are
regulated by HSF-1 in a HS-independent manner. HSF-1 therefore coordinates
various physiological processes in C. elegans, and HSF-1 activity may be
coordinated across tissues by nuclear hormone receptor and epidermal growth
factor receptor signaling. CONCLUSION: This work provides genome-wide HSF-1
regulatory networks in C. elegans that are both heat stress-dependent and
independent. We show that HSF-1 is responsible for regulating many genes outside
of classical heat stress-responsive genes, including genes involved in
development, metabolism, and aging. The findings that a nuclear hormone receptor
may coordinate the HS-induced HSF-1 transcriptional response, while an epidermal
growth factor receptor may coordinate the HS-independent response, indicate that
these factors could promote cell non-autonomous signaling that occurs through HSF
1. Finally, this work highlights the genes involved in cuticle structure as
important HSF-1 targets that may play roles in promoting both cytoprotection as
well as longevity.
PMID- 27496168
TI - Arterial Path Length for Arterial Stiffness: Methodological Consideration.
AB - BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) is the most established
measure of central arterial stiffness and is calculated by dividing the distance
travelled by the pulse wave by the pulse transit time. However, there is no
universally accepted standardized measurement of pulse travel distance for cfPWV.
This study sought to assess validity and convertibility of 2 most frequently used
travel distance estimations, and create the simple and useful conversion equation
to unify cfPWV values obtained with different methodologies for pulse travel
distance. METHODS: In a total of 227 adults, cfPWV was calculated using 2
different pulse travel distances: suprasternum-femoral distance minus
suprasternum-carotid distance (the subtraction method) and carotid-femoral
straight distance * 0.8 (the 80% method). They were compared against 3D arterial
tracing via magnetic resonance imaging (MRI). RESULTS: The subtraction method
underestimated travel distance and cfPWV by 8.7% although correlations with the
MRI reference values were significant. The 80% method provided more reliable
cfPWV, showing a stronger linearity (r = 0.96, P < 0.0001) and a better agreement
with the MRI-based reference value (+0.02+/-0.54 m/s). Values of cfPWV were
influenced primarily by pulse transit time, explaining ~80% of the variation in
cfPWV, and the contribution of pulse travel distance was relatively small
irrespective of how the travel distance was measured. After the application of
the conversion factor (the 80% method = the subtraction method * 1.1), cfPWV
values obtained with both methods were strongly correlated and estimation errors
were comparable (+0.03+/-0.75 m/s). CONCLUSION: Our findings indicate that the
subtraction method and the 80% method can provide equivalent cfPWV values by the
application of a simple conversion factor.
PMID- 27496169
TI - Modified posteromedial approach for treatment of posterior pilon variant
fracture.
AB - BACKGROUND: Posterior pilon variant fracture is a recently described posterior
malleolus fracture characterized by the involvement of both posterolateral and
posteromedial malleolar fragment. The associated surgical approach remains
controversial. The aim of this study was to present the application of modified
posteromedial approach in the treatment for posterior pilon variant fracture.
METHODS: Sixteen patients were identified with posterior pilon variant fractures.
All fractures were operated via modified posteromedial approach. Fragment length
ratio, area ratio and height were measured as morphologic assessments. The
clinical outcome was evaluated with American Orthopaedic Foot & Ankle Society
ankle-hind foot score and visual analogue scale. Radiological images were
evaluated using osteoarthritis-score. RESULTS: According to the radiological
measurements, the average fragment length ratio of posteromedial and
posterolateral fragment was 25.3 and 31.5 % respectively. All fractures healed
within a mean period of 13.1 weeks without malalignment or articular step-off.
Fourteen patients were followed up, and all achieved good or excellent ankle
function. The average score of American Orthopaedic Foot & Ankle Society and
visual analogue scale at rest, motion and weight bearing walking was 85.6 and
0.25, 0.81, 1.31 respectively. CONCLUSION: Modified posteromedial approach
provides an alternative surgical treatment for posterior pilon variant fractures,
and the short-term outcome was good.
PMID- 27496170
TI - Vaccination against pancreas disease in Atlantic salmon, Salmo salar L., reduces
shedding of salmonid alphavirus.
AB - Salmon pancreas disease virus, often referred to as salmonid alphavirus (SAV),
causes pancreas disease (PD) in European salmonids. SAV transmits horizontally
from fish shedding virus into the water and ocean currents are believed to be a
main contributor of viral spread between marine farms. Vaccination against PD is
previously shown to reduce mortality and severity of clinical PD. In this study,
we demonstrate that vaccination against PD significantly reduces viral shedding
from infected individuals. The results suggest that PD vaccination can be an
important tool to reduce the infection pressure, a known key risk for PD
outbreaks at neighbouring farms.
PMID- 27496171
TI - Online psychophysics: reaction time effects in cognitive experiments.
AB - Using the Internet to acquire behavioral data is currently on the rise. However,
very basic questions regarding the feasibility of online psychophysics are still
open. Here, we aimed to replicate five well-known paradigms in experimental
psychology (Stroop, Flanker, visual search, masked priming, attentional blink) in
three settings (classical "lab", "web-in-lab", "web") to account for possible
changes in technology and environment. Lab and web-in-lab data were both acquired
in an in-lab setting with lab using "Gold Standard" methods, while web-in-lab
used web technology. This allowed for a direct comparison of potential
differences in acquisition software. To account for additional environmental
differences, the web technology experiments were published online to participate
from home (setting web), thereby keeping the software and experimental design
identical and only changing the environmental setting. Our main results are:
First, we found an expected fixed additive timing offset when using web
technology (M = 37 ms, SD = 8.14) and recording online (M = 87 ms, SD = 16.04) in
comparison to lab data. Second, all task-specific effects were reproduced except
for the priming paradigm, which couldn't be replicated in any setting. Third,
there were no differences in error rates, which are independent of the timing
offset. This finding further supports the assumption of data equality over all
settings. Fourth, we found that browser type might be influencing absolute
reaction times. Together, these results contribute to the slowly but steadily
growing literature that online psychophysics is a suitable complement - or even
substitute - to lab data acquisition.
PMID- 27496172
TI - "Going to town": Large-scale norming and statistical analysis of 870 American
English idioms.
AB - An idiom is classically defined as a formulaic sequence whose meaning is
comprised of more than the sum of its parts. For this reason, idioms pose a
unique problem for models of sentence processing, as researchers must take into
account how idioms vary and along what dimensions, as these factors can modulate
the ease with which an idiomatic interpretation can be activated. In order to
help ensure external validity and comparability across studies, idiom research
benefits from the availability of publicly available resources reporting ratings
from a large number of native speakers. Resources such as the one outlined in the
current paper facilitate opportunities for consensus across studies on idiom
processing and help to further our goals as a research community. To this end,
descriptive norms were obtained for 870 American English idioms from 2,100
participants along five dimensions: familiarity, meaningfulness, literal
plausibility, global decomposability, and predictability. Idiom familiarity and
meaningfulness strongly correlated with one another, whereas familiarity and
meaningfulness were positively correlated with both global decomposability and
predictability. Correlations with previous norming studies are also discussed.
PMID- 27496173
TI - Efficient n-gram analysis in R with cmscu.
AB - We present a new R package, cmscu, which implements a Count-Min-Sketch with
conservative updating (Cormode and Muthukrishnan Journal of Algorithms, 55(1), 58
75, 2005), and its application to n-gram analyses (Goyal et al. 2012). By writing
the core implementation in C++ and exposing it to R via Rcpp, we are able to
provide a memory-efficient, high-throughput, and easy-to-use library. As a proof
of concept, we implemented the computationally challenging (Heafield et al. 2013)
modified Kneser-Ney n-gram smoothing algorithm using cmscu as the querying
engine. We then explore information density measures (Jaeger Cognitive
Psychology, 61(1), 23-62, 2010) from n-gram frequencies (for n=2,3) derived from
a corpus of over 2.2 million reviews provided by a Yelp, Inc. dataset. We
demonstrate that these text data are at a scale beyond the reach of other more
common, more general-purpose libraries available through CRAN. Using the cmscu
library and the smoothing implementation, we find a positive relationship between
review information density and reader review ratings. We end by highlighting the
important use of new efficient tools to explore behavioral phenomena in large,
relatively noisy data sets.
PMID- 27496174
TI - Trial-by-trial identification of categorization strategy using iterative decision
bound modeling.
AB - Identifying the strategy that participants use in laboratory experiments is
crucial in interpreting the results of behavioral experiments. This article
introduces a new modeling procedure called iterative decision-bound modeling
(iDBM), which iteratively fits decision-bound models to the trial-by-trial
responses generated from single participants in perceptual categorization
experiments. The goals of iDBM are to identify: (1) all response strategies used
by a participant, (2) changes in response strategy, and (3) the trial number at
which each change occurs. The new method is validated by testing its ability to
identify the response strategies used in noisy simulated data. The benchmark
simulation results show that iDBM is able to detect and identify strategy
switches during an experiment and accurately estimate the trial number at which
the strategy change occurs in low to moderate noise conditions. The new method is
then used to reanalyze data from Ell and Ashby (2006). Applying iDBM revealed
that increasing category overlap in an information-integration category learning
task increased the proportion of participants who abandoned explicit rules, and
reduced the number of training trials needed to abandon rules in favor of a
procedural strategy. Finally, we discuss new research questions made possible
through iDBM.
PMID- 27496176
TI - Factors Associated with Self-Reported Cervical Cancer Screening Among Women Aged
18 Years and Older in the United States.
AB - In 2016, an estimated 4120 women will die as a result of cervical cancer. The
objective of this study was to examine the factors associated with cervical
cancer screening among women 18 years of age and older in the United States
(U.S.). Using the 2012 Behavioral Risk Factor Surveillance System survey, women
over the age of 18 in the U.S. were examined to assess factors associated with
cervical cancer screening. Analyses were conducted using SAS 9.2. Of the 272,692
study participants, 258,496 (95 %) had obtained cervical cancer screening. After
adjusting for demographic and socioeconomic factors, being non-Hispanic White,
Hispanic or Latino, Asian, Native Hawaiian or Other Pacific Islander, in the age
group 18-44 years and 75 years and above, having less than a high school
education and an annual household income of less than a $25,000, having never
married, and residing in the West region of the U.S. reduced the likelihood of
participation in cervical cancer screening. Also, after adjusting for demographic
and socioeconomic factors, being between the ages of 45-74 years of age, having
more than a high school education, having a higher income, and residing in the
South region of the U.S. increased the likelihood of participation in cervical
cancer screening. The results of this study suggest that socio-demographic
factors and region of residence are predictors of cervical cancer screening.
These findings highlight the need to identify potential prevention strategies to
promote cervical cancer screening among at-risk populations and groups.
PMID- 27496175
TI - Functional prediction of differentially expressed lncRNAs in HSV-1 infected human
foreskin fibroblasts.
AB - BACKGROUND: One of the most important functions of long noncoding RNAs (lncRNAs)
is to control protein coding gene transcription by acting locally in cis, or
remotely in trans. Herpes Simplex Virus type I (HSV-1) latently infects over 80 %
of the population, its reactivation from latency usually results in productive
infections in human epithelial cells, and is responsible for the common cold
sores and genital Herpes. HSV-1 productive infection leads to profound changes in
the host cells, including the host transcriptome. However, how genome wide
lncRNAs expressions are affected by the infection and how lncRNAs expression
relates to protein coding gene expression have not been analyzed. METHODS: We
analyzed differentially expressed lncRNAs and their potential targets from RNA
seq data in HSV-1 infected human foreskin fibroblast (HFF) cells. Based on
correlations of expression patterns of differentially expressed protein-coding
genes and lncRNAs, we predicted that these lncRNAs may regulate, either in cis or
in trans, the expression of many cellular protein-coding genes. RESULTS: Here we
analyzed HSV-1 infection induced, differentially expressed lncRNAs and predicted
their target genes. We detected 208 annotated and 206 novel differentially
expressed lncRNAs. Gene Ontology and Pathway enrichment analyses revealed
potential lncRNA targets, including genes in chromatin assembly, genes in
neuronal development and neurodegenerative diseases and genes in the immune
response, such as Toll-like receptor signaling and RIG-I-like receptor signaling
pathways. CONCLUSIONS: We found that differentially expressed lncRNAs may
regulate the expression of many cellular protein-coding genes involved in
pathways from native immunity to neuronal development, thus revealing important
roles of lncRNAs in the regulation of host transcriptional programs in HSV-1
infected human cells.
PMID- 27496177
TI - Pregnancy complications in singleton pregnancies with isolated fetal heart
defects.
AB - INTRODUCTION: As the prenatal detection rates of congenital heart defects (CHDs)
increase, obstetricians are more frequently faced with pregnancies complicated by
a fetal CHD. Congenital anomalies in general are associated with preterm birth
and fetal demise. The aim of this study was to gain insight into the prevalence
of preterm birth and fetal demise in singleton pregnancies with fetuses with
isolated CHDs. MATERIAL AND METHODS: A geographical cohort study was performed in
a large region in the Netherlands. Fetuses and infants from singleton pregnancies
diagnosed with severe isolated CHD, born between 1 January 2002 and 1 January
2012, were included. All cases in the CHD cohort were assessed for preterm birth
or fetal demise. The proportions of preterm birth and fetal demise were compared
with those in a control group and odds ratios were calculated. RESULTS: The
proportion of preterm births in the CHD cohort (n = 1013) was 9.1% (95% CI 7.3
10.9) compared with 5.6% (95% CI 5.4-5.8) in the control group, with an odds
ratio of 1.7 (95% CI 1.4-2.1). The preterm birth started spontaneously in 49.5%
and 38.4% were induced. In 15 cases fetal demise occurred (1.5%; 95% CI 0.8-2.2),
compared with 0.7% (95% CI 0.6-0.8) in the control group, odds ratio 2.0 (95% CI
1.2-3.4). CONCLUSIONS: Higher rates of preterm birth and fetal demise occur in
fetuses with isolated CHD compared with the general population. Prenatal
specialists should be vigilant for signs of heart failure, premature closure of
the foramen ovale or fetal distress in fetuses with isolated CHDs.
PMID- 27496179
TI - Using Genetically Encodable Self-Assembling Gd(III) Spin Labels To Make In-Cell
Nanometric Distance Measurements.
AB - Double electron-electron resonance (DEER) can be used to study the structure of a
protein in its native cellular environment. Until now, this has required
isolation, in vitro labeling, and reintroduction of the protein back into the
cells. We describe a completely biosynthetic approach that avoids these steps. It
exploits genetically encodable lanthanide-binding tags (LBT) to form self
assembling Gd(III) metal-based spin labels and enables direct in-cell
measurements. This approach is demonstrated using a pair of LBTs encoded one at
each end of a 3-helix bundle expressed in E. coli grown on Gd(III) -supplemented
medium. DEER measurements directly on these cells produced readily detectable
time traces from which the distance between the Gd(III) labels could be
determined. This work is the first to use biosynthetically produced self
assembling metal-containing spin labels for non-disruptive in-cell structural
measurements.
PMID- 27496178
TI - A unified approach towards Trypanosoma brucei functional genomics using Gibson
assembly.
AB - Trypanosoma brucei is the causative agent of human African trypanosomiasis and
nagana in cattle. Recent advances in high throughput phenotypic and interaction
screens have identified a wealth of novel candidate proteins for diverse
functions such as drug resistance, life cycle progression, and cytoskeletal
biogenesis. Characterization of these proteins will allow a more mechanistic
understanding of the biology of this important pathogen and could identify novel
drug targets. However, methods for rapidly validating and prioritizing these
potential targets are still being developed. While gene tagging via homologous
recombination and RNA interference are available in T. brucei, a general strategy
for creating the most effective constructs for these approaches is lacking. Here,
we adapt Gibson assembly, a one-step isothermal process that rapidly assembles
multiple DNA segments in a single reaction, to create endogenous tagging,
overexpression, and long hairpin RNAi constructs that are compatible with well
established T. brucei vectors. The generality of the Gibson approach has several
advantages over current methodologies and substantially increases the speed and
ease with which these constructs can be assembled.
PMID- 27496181
TI - Myeloma bone disease: Progress in pathogenesis.
AB - Myeloma bone disease (MBD) is one of the most serious complications of multiple
myeloma (MM) and the most severe cause of MM morbidity. Dysregulation of
osteoblast and osteoclast cells plays key roles in MBD. In the bone marrow
microenvironment, myeloma cells, osteoblasts, osteoclasts and bone marrow stromal
cells can secrete multiple cytokines, categorized as osteoclast cell activating
factors (OAFs) and osteoblast cell inactivating factors, which have been
discovered to participate in bone metabolism and contribute to the pathogenesis
of MBD. Several signaling pathways related to these cytokines were also revealed
in the MBD pathogenesis. To better understand the pathogenesis of MBD and
therefore the potential therapeutic targets of this disease, we will summarize
recent study progress in the factors and underlying signaling pathways involved
in the occurrence and development of MBD.
PMID- 27496182
TI - Iris Krass.
PMID- 27496180
TI - Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS)
trial: a randomised controlled trial.
AB - BACKGROUND: For around a third of people with a diagnosis of schizophrenia, the
condition proves to respond poorly to treatment with many typical and atypical
antipsychotics. This is commonly referred to as treatment-resistant
schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for
people whose symptoms are considered treatment-resistant to antipsychotic
medication. However, 30-40 % of such conditions will have an insufficient
response to the drug. Cognitive behavioural therapy has been shown to be an
effective treatment for schizophrenia when delivered in combination with
antipsychotic medication, with several meta-analyses showing robust support for
this approach. However, the evidence for the effectiveness of cognitive
behavioural therapy for people with a schizophrenia diagnosis whose symptoms are
treatment-resistant to antipsychotic medication is limited. There is a clinical
and economic need to evaluate treatments to improve outcomes for people with such
conditions. METHODS/DESIGN: A parallel group, prospective randomised, open,
blinded evaluation of outcomes design will be used to compare a standardised
cognitive behavioural therapy intervention added to treatment as usual versus
treatment as usual alone (the comparator group) for individuals with a diagnosis
of schizophrenia for whom an adequate trial of clozapine has either not been
possible due to tolerability problems or was not associated with a sufficient
therapeutic response. The trial will be conducted across five sites in the United
Kingdom. DISCUSSION: The recruitment target of 485 was achieved, with a final
recruitment total of 487. This trial is the largest definitive, pragmatic
clinical and cost-effectiveness trial of cognitive behavioural therapy for people
with schizophrenia whose symptoms have failed to show an adequate response to
clozapine treatment. Using a prognostic risk model, baseline information will be
used to explore whether there are identifiable subgroups for which the treatment
effect is greatest. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99672552
. Registered 29(th) November 2012.
PMID- 27496183
TI - The importance of n-6/n-3 fatty acids ratio in the major depressive disorder.
AB - This review aims to clarify the relation between the ratio of omega-6 to omega-3
fatty acids and the development of depression. It is explained how these fatty
acids are involved in the production of eicosanoids and how these fatty acids can
affect the membrane fluidity, by their incorporation into membrane phospholipids.
In addition, it is described how omega-3 derivatives are shown to regulate gene
transcription. In view of the pathophysiology of depression, the mechanisms of
how an altered ratio of omega-6 to omega-3 could be involved in depression are
discussed. Possible mechanisms could include an increased production of pro
inflammatory cytokines, which can activate the HPA axis and a changed membrane
fluidity, which potentially affects membrane bound enzymes, ion channels,
receptor activity and neurotransmitter binding. In view of clinical trials, it is
also discussed whether omega-3 supplementation could have a beneficial effect in
the treatment of depressive patient. There are strong indications that an
increased ratio of membrane omega-6 to omega-3 is involved in the pathogenesis of
depression and so far, omega-3 supplementation has shown positive effects in
clinical trials.
PMID- 27496184
TI - Multiplicity of effects and health benefits of resveratrol.
AB - Resveratrol is mainly found in grapes and red wine, also in some plants and
fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries.
Moreover, nowadays this compound is available as purified preparation and dietary
supplement. Resveratrol provides a wide range of benefits, including
cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood
glucose-lowering and anticancer activities, hence it exhibits a complex mode of
action. During the recent years, these properties have been widely studied in
animal and human models, both in vitro and in vivo. This paper is intended to
present information published during the recent years on the biological
activities and multiple effects of resveratrol.
PMID- 27496185
TI - Association between clinical parameters and ST-segment resolution after primary
percutaneous coronary intervention in patients with acute ST-segment elevation
myocardial infarction.
AB - BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate and compare
various parameters between complete and incomplete ST-segment resolution (STR)
patients' groups and to identify associates of STR in patients with acute ST
segment elevation myocardial infarction (STEMI) after primary percutaneous
coronary intervention (PPCI) (primary outcome). MATERIALS AND METHODS: A total of
203 consecutive patients were divided into two groups according to the degree of
STR: <70% (incomplete) and >=70% (complete resolution) 5-15min after the PPCI.
The cardiovascular risk factors, sex, Killip class, Thrombolysis in Myocardial
Infarction (TIMI) flow, symptom-onset-to-balloon time and door-to-balloon time,
and adverse cardiovascular events (secondary outcome) were assessed and compared
between two groups. RESULTS: There were 147 patients with incomplete STR and 56
patients with complete STR. Patients with complete STR were younger, had lower
Killip class, shorter duration of the chest pain and were less likely to have
anterior myocardial infarction (AMI). Patients in the incomplete STR group had
longer symptom-onset-to-balloon and door-to-balloon intervals. TIMI3 flow after
PPCI was more common in the complete STR group. TIMI flow <=2 after PCI, AMI and
symptom onset-to-balloon time were inversely associated with STR (beta
coefficients -28.635, -28.611, and -0.917, respectively). AMI (OR=29.9), symptom
onset-to-balloon time (OR=1.7) and patient's age (OR=1.1) were associated with an
increased likelihood of having incomplete STR. CONCLUSIONS: Patients with
complete STR were younger, had lower Killip class, shorter duration of STEMI,
were less likely to have AMI, were more likely to recover TIMI3 flow. Age, TIMI
flow grade 2 or less after PPCI, AMI and symptom-onset-to-balloon time were
associated with STR.
PMID- 27496186
TI - Comparison of the Ponseti method versus early tibialis anterior tendon transfer
for idiopathic clubfoot: A prospective randomized study.
AB - OBJECTIVE: The aim of the study was to compare functional and radiological
outcomes in clubfoot patients treated by early Tibialis anterior tendon transfer
and Ponseti method. MATERIALS AND METHODS: A prospective, randomized study was
conducted. A total of 39 children with a mean age of 17.05 days (55 clubfeet)
were randomly allocated into one of two groups: first (conservative Ponseti
method) group (n=28) or second (early tibialis anterior tendon transfer [TATT])
group (n=27). Foot function and radiographic measurements were evaluated. The
condition of the subjects was observed until they reached the age of 2 years.
RESULTS: The clinical and radiological data did not differ between groups at the
age of 6 months. No statistically significant difference regarding Pirani and
Dimeglio scale among the groups was observed at the last follow-up. A
statistically significant difference was observed in the foot dorsal flexion; it
was lower in the second group (P=0.03). Other clinical parameters did not differ
between groups. According radiographic data, only the talocalcaneal angle (TCA)
was significantly higher in the second group (P=0.003). Children who underwent
TATT were 5.00-fold (P=0.002) and 1.67-fold (P=0.017) more likely to have TCA
larger than 30 degrees (which reflects the normal range of the TCA) in DP and
lateral views, respectively, and 3.40-fold (P=0.019) more likely to have foot
dorsal flexion of less than 15 degrees than their counterparts undergoing the
conservative Ponseti treatment. CONCLUSIONS: Early TATT allowed a significant
reduction in the brace wear duration and resulted in the same outcomes as using
the Ponseti method. Additionally, TATT can provide some improvement of hindfoot
varus. However, a possible weakening of dorsiflexion should be also taken into
account. Our experience has shown the need for a larger sample and longer term
studies.
PMID- 27496188
TI - Genetic linkage studies of a North Carolina macular dystrophy family.
AB - BACKGROUND AND OBJECTIVE: North Carolina macular dystrophy (NCMD) is a very rare
autosomal dominant hereditary disease. Up to date there are three types of NCMD
described and consequently named macular dystrophy, retinal: MCDR1, MCDR2 and
MCDR3. The aim of this study was to perform linkage and copy number variation
analysis for the family affected by NCMD followed by the selected candidate gene
sequencing. MATERIALS AND METHODS: This study concerned a 3-generation, non
consanguineous Latvian family with NCMD. Genome-wide scan, copy number variation
and non-parametric linkage analysis was performed. Analysis resolved the locus of
interest to the 5p15.33 region. Two of the genes, iroquois homeobox 2 (IRX2) and
iroquois homeobox 4 (IRX4), were selected and sanger sequencing was performed.
RESULTS: Linkage analysis indicated a region on chromosome 5 for the analyzed
family, corresponding to a genetic locus previously described for MCDR3 (5p15
p13). Chromosomal aberrations were not identified in the affected family members.
An upstream intron variant (NM_001278634: c.-139G > A (rs6876836)) in IRX4 gene
segregated with NCMD phenotype in the analyzed family. CONCLUSIONS: It is
unlikely to be the causative mutation of NCMD due to its high minor allele
frequency 0.3532. Therefore, the role of IRX2 and IRX4 genes in the pathogenesis
of NCMD has not been proved. Considerable variability in visual acuity between
individuals of the same age group in all the families examined was noted. No
overlap between NCMD grade and family generation was seen in the family described
in the present study.
PMID- 27496187
TI - Pilot study of safety and efficacy of polyprenols in combination with coenzyme
Q10 in patients with statin-induced myopathy.
AB - BACKGROUND AND OBJECTIVE: Statin-induced myopathy (SIM) has been partially
attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test
the safety and efficacy of plant polyprenols in combination with CoQ10 for
alleviation of SIM. MATERIALS AND METHODS: In an open-label, one-center
prospective pilot study patients with SIM received conifer-tree needle
polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were
evaluated according to symptom severity score (0-10), creatine kinase (CK)
levels, exercise test, dynamometry, complete blood count, clinical biochemistry
and electrocardiography. RESULTS: Of the 14 patients, 11 completed the study per
protocol. Two patients withdrew consent due to travels abroad, and it was
discontinued for one patient with stage 3 chronic kidney disease due to
asymptomatic elevations of liver enzymes at week 4. No safety parameters changed
significantly in per protocol group. Non-significant increase of CK levels was
observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved
significantly (P<0.001 and P=0.018, respectively). Muscle pain completely
disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared
in two patients. Four patients assessed improvement strong enough to consider
increase of statin dose. No changes were observed in exercise test or
dynamometry. CONCLUSIONS: Conifer-tree polyprenols in combination with CoQ10 may
be generally safe in patients with SIM, but caution should be exercised in
patients with glomerular filtration rate <60mL/min and routine monitoring of the
liver enzymes and CK is advocated in all patients. The observed efficacy provides
the rationale for a larger, double-blind controlled study with polyprenols.
PMID- 27496189
TI - BCG-SSI((r)) vaccine-associated lymphadenitis: Incidence and management.
AB - BACKGROUND AND OBJECTIVE: There is a high incidence of childhood tuberculosis in
Latvia, including children aged less than 1 year, while BCG-associated
lymphadenitis is one of the most frequent adverse events requiring surgical
treatment. The aim of this study was to analyze the incidence of purulent BCG
adenitis through-out the population of Latvia after the introduction of BCG
SSI((r)) vaccine and to evaluate the treatment results. MATERIAL AND METHODS: The
study included 194 patients. All patients had received the BCG-SSI((r)) vaccine
during the first week of life routinely or at a later time according to the
indications. The indications for surgical treatment were lymph node destruction
also affecting the skin. All patients in this study received surgical treatment -
the affected lymph node extirpation. RESULTS: The mean age of the patients was
5.12+/-0.96 months. A total of 172 patients had purulent axillar lymphadenitis,
14 had purulent supraclavicular lymphadenitis, 8 patients had lymphadenitis at
both localizations. During the whole study period the incidence of BCG adenitis
varied from 0.02% to 0.36%, while the mean rate was 0.11%+/-0.08% from 184,068
vaccinated children during the study period. We observed an increasing trend in
the incidence of BCG lymphadenitis during the study period. The primary and
complete healing rate at the end of period was 99.5% (n=193) following an
affected lymph node extirpation. The mean hospitalization time after the
operation was 3.71+/-0.18 days. CONCLUSIONS: The incidence of BCG-SSI((r))
vaccine associated purulent lymphadenitis varied widely with an increasing trend,
followed by the return to the product characteristic limits. Indications for the
surgical treatment should not be changed. Extirpation of the purulent BCG
adenitis is a safe treatment method and leads to the primary wound healing in the
majority of cases.
PMID- 27496190
TI - Pay for performance of Estonian family doctors and impact of different practice-
and patient-related characteristics on a good outcome: A quantitative assessment.
AB - BACKGROUND AND OBJECTIVE: Several practice- and patient-related characteristics
are reported to have an influence on a good quality outcome. Estonia started the
pay-for-performance (P4P) system for family doctors (FDs) in 2006. Every year the
number of FDs participating in P4P has increased, but only half of the FDs
achieved good outcome. The aim of this study was to find out which practice- and
patient-related characteristics could have an impact on a good outcome. MATERIALS
AND METHODS: The study was conducted using the database from the Estonian Health
Insurance Fund. All working FDs were divided into two groups (with "good" and
"poor" outcomes) according their achievements in P4P. We chose characteristics
which described structure (practice list size, number of doctors, composition of
FDs list: age, number of chronically ill patients) during the observation period
2006-2012. RESULTS: During the observation period 2006-2012, the number of FDs
with a good outcome in P4P increased from 6% (2006) to 53% (2012). The high
number of FDs in primary care teams, longer experience of participation in P4P
and the smaller number of patients on FDs' lists all have an impact on a good
outcome. The number of chronically ill patients in FDs lists has no significant
effect on an outcome, but P4P increases the number of disease-diagnosed patients.
CONCLUSIONS: Different practice and patient-related characteristics have an
impact on a good outcome. As workload increases, smaller lists of FDs patients or
increased staff levels are needed in order to maintain a good outcome.
PMID- 27496191
TI - Problematic computer game use as expression of Internet addiction and its
association with self-rated health in the Lithuanian adolescent population.
AB - BACKGROUND AND OBJECTIVE: Computers and the Internet have become an integral part
of today's life. Problematic gaming is related to adolescent's health. The aim of
our study was to evaluate the prevalence of Internet addiction among 13-18-year
old schoolchildren and its relation to sex, age, and time spent playing computer
games, game type, and subjective health evaluation. MATERIALS AND METHODS: A
total of 1806 schoolchildren aged 13-18 years were interviewed. The evaluation of
Internet addiction was conducted by the Diagnostic Questionnaire according to
Young's methodology. The relation between the choice of computer games type, time
spent while playing computer games and respondents' Internet addiction were
assessed by using multivariate logistic regression analysis. RESULTS: One-tenth
(10.6%) of the boys and 7.7% of the girls aged 13-18 years were Internet
addicted. Internet addiction was associated with the type of computer game
(action or combat vs. logic) among boys (OR=2.42; 95% CI, 1.03-5.67) and with the
amount of time spent playing computer games per day during the last month (>=5
vs. <5h) among girls (OR=2.10; 95% CI, 1.19-3.70). The boys who were addicted to
the Internet were more likely to rate their health poorer in comparison to their
peers who were not addicted to the Internet (OR=2.48; 95% CI, 1.33-4.62).
CONCLUSIONS: Internet addiction was significantly associated with poorer self
rated health among boys.
PMID- 27496192
TI - Dimethylfumarate induces cell cycle arrest and apoptosis via regulating
intracellular redox systems in HeLa cells.
AB - Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an
anti-tumor drug. This study was designed to investigate the effects and
underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured
and treated with 0, 50, 100, 150, and 200 MUM DMF, respectively. After 24 h, cell
growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle
was examined using flow cytometry. In addition, cell apoptosis was detected by
Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and
poly-ADP-ribose polymerase (PARP) were detected using western blotting. The redox
related factors were then assessed. Furthermore, all of the indicators were
detected in HeLa cells after combined treatment of DMF and N-acetyl-L-cysteine
(NAC, an oxygen-free radical scavenger). The cell number and cell growth of HeLa
were obviously inhibited by DMF in a dose-dependent manner, as the cell cycle was
arrested at G0/G1 phase (P < 0.05). The apoptotic HeLa cells were markedly
increased, and the expression levels of caspase-3 and PARP were significantly
increased in a DMF concentration-dependent way (P < 0.05). Meanwhile, loss of
?Psim, increase in reactive oxygen species and O2.-, and the decrease in catalase
activity and glutathione (GSH) level were found after DMF treatment (P < 0.05).
All these changes were significantly attenuated and even completely disappeared
by adding NAC (P < 0.05). In conclusion, the cytotoxicity of DMF on cell
proliferation and apoptosis of HeLa cells was mainly related to the intracellular
redox systems by depletion of intracellular GSH.
PMID- 27496193
TI - Directed differentiation of human embryonic stem cells into keratinocyte
progenitors in vitro: an attempt with promise of clinical use.
AB - Human embryonic stem cells (hESCs) can differentiate into all somatic lineages
including stratified squamous epithelia. Thus, efficient methods are required to
direct hESC differentiation to obtain a pure subpopulation for tissue
engineering. The study aimed to assess the effects of retinoic acid (RA), bone
morphogenetic protein-4 (BMP4), and ascorbic acid (AA) on the differentiation of
hESCs into keratinocyte progenitors in vitro. The first media contained AA and
BMP4; the second contained RA, AA, and BMP4; the third was commercial-defined
keratinocyte serum-free medium, which was used to differentiate H9 hESCs (direct
approach) or embryoid bodies (EBs) (indirect approach) into keratinocyte
progenitors. Real-time RT-PCR, immunofluorescence, and flow-cytometry were used
to characterize the differentiated cells. Cells induced by AA + BMP4 + RA showed
the typical epithelial morphology, while cells induced by AA + BMP4 showed
multiple appearances. CK14 and p63 messenger RNA (mRNA) expressions in the AA +
BMP4 + RA-treated cells were higher than those of the AA + BMP4-treated cells
(CK14: 22.4-fold; p63: 84.7-fold). Epithelial marker CK18 mRNA expressions at 14
d of differentiation and keratinocyte marker CK14 and transcription factor p63
mRNA expressions at 35 d of differentiation were higher in cells differentiated
from hESCs compared with those differentiated from EBs (CK18 10.51 +/- 3.26 vs.
6.67 +/- 1.28; CK14 9.27 +/- 3.61 vs. 5.32 +/- 1.86; p63 0.73 +/- 0.06 vs. 0.44
+/- 0.12, all P < 0.05) After hESC induction by AA+BMP4+RA, CK14 mRNA expression
was upregulated after day 21, peaking by 35 d of differentiation. Combined RA,
BMP4, and AA could effectively induce differentiation of hESCs into keratinocyte
progenitors in vitro. These keratinocytes could be used for oral mucosa and skin
tissue engineering.
PMID- 27496194
TI - Murine Flt3 ligand-generated plasmacytoid and conventional dendritic cells
display functional differentiation in activation, inflammation, and antigen
presentation during BCG infection in vitro.
AB - Dendritic cells (DCs) are composed of distinct subsets. Their immunologic
functions (especially in pathogenic infection, such as with mycobacteria) are
poorly understood, largely because of their rarity and difficulty of preparation.
We used the murine Fms-like tyrosine kinase 3 (Flt3) ligand to generate
conventional DCs (FL-cDCs) and plasmacytoid DCs (FL-pDCs) and further evaluated
their immunological responses to bacillus Calmette-Guerin (BCG) infection in
vitro. BCG cells were observed inside both FL-cDCs and FL-pDCs by confocal
microscopy, as confirmed by flow cytometric analysis showing a low infection rate
of approximately 6 %, which was similar to in vivo results. The CD40, CD80, CD86,
and MHC-II proteins were significantly upregulated in both FL-cDCs and -pDCs
beginning at 4 h post-BCG exposure. FL-pDCs secreted TNF-alpha and IL-6 earlier
and at significantly higher levels in the first 12 h following infection, but
demonstrated delayed and weak activation and maturation compared to FL-cDCs.
Although both subsets proved capable of presenting a mycobacterial antigen, FL
pDCs exhibited weaker activity in this respect than did FL-cDCs. In summary, the
existence of FL-generated cDCs and pDCs imply functional differentiation in
activation, inflammation, and antigen presentation, although both cells types
participated extensively in the immune response to BCG infection.
PMID- 27496195
TI - Systematic review and critical appraisal of transitional care programmes in
rheumatology.
AB - OBJECTIVES: Identify existing models of transitional care in rheumatic and
musculoskeletal diseases (RMD), describe their strengths and weaknesses, and
provide support to a consensus initiative to develop recommendations for
transitional care. METHODS: A systematic review was conducted to identify
publications describing transition programmes in RMD. Eligibility for inclusion
required detailed description of the programme. Descriptive information was
collected, including country of the programme, target diseases and ages of the
patients, resources, elements of the transition process and, when described,
outcomes and quality indicators. Quality assessment of the programmes included:
level of definition and the evidence base for the programme, availability of
quality indicators and evidence of effectiveness. RESULTS: Overall, 27 articles
were identified and evaluated, related to 8 programmes in 6 countries: 4 covered
all RMDs, 3 specific for patients with juvenile idiopathic arthritis (JIA) and 1
programme generic for chronic diseases and adapted for RMD. Core elements of
these transition programmes included the following: a written transition policy;
patient individualised planning and flexibility of transitional care; designation
of transition coordinator role; acquisition of knowledge and skills in self
management of care; decision making, shared care and communication between
paediatric and adult health care provider teams and a planned transfer to adult
rheumatology. Only 2 provided evidence of effectiveness according to previously
specified outcome measures. CONCLUSIONS: Transitional care programmes in RMDs are
variable in their structures, staffing and processes. There are no standardised
measures of outcome or effectiveness. This information provides important
valuable insights and strategies to develop transitional care in RMD.
PMID- 27496196
TI - Lung adenocarcinoma harboring concomitant SPTBN1-ALK fusion, c-Met
overexpression, and HER-2 amplification with inherent resistance to crizotinib,
chemotherapy, and radiotherapy.
AB - Crizotinib is a multi-targeted tyrosine kinase inhibitor (TKI) with activity
against mesenchymal-epithelial transition factor (MET) and anaplastic lymphoma
kinase (ALK). However, the concomitant oncogenic drivers may affect the
sensitivity of crizotinib. Herein, we present a 69-year-old never-smoker Chinese
male with advanced lung adenocarcinoma harboring concomitant spectrin beta non
erythrocytic 1 (SPTBN1)-ALK fusion, c-Met overexpression, and human epidermal
growth factor receptor-2 (HER-2) amplification with inherent resistance to
crizotinib, chemotherapy, and radiotherapy. Although the patient received timely
and comprehensive treatment, the overall survival was only 8 months. Therefore, c
Met overexpression, HER-2 gene amplification, and SPTBN1-ALK gene fusion can
coexist in lung adenocarcinoma and may become a potential biomarker of cancer
refractory to crizotinib, chemotherapy, and radiotherapy as well as of a
relatively poor prognosis. In addition, the novel SPTBN1-ALK fusion gene may
become a potential target for anti-tumor therapy.
PMID- 27496197
TI - Spectrum optimization for computed radiography mammography systems.
AB - PURPOSE: Technical quality assurance is a key issue in breast screening
protocols. While full-field digital mammography systems produce excellent image
quality at low dose, it appears difficult with computed radiography (CR) systems
to fulfill the requirements for image quality, and to keep the dose below the
limits. However, powder plate CR systems are still widely used, e.g., they
represent ~30% of the devices in the Austrian breast cancer screening program.
For these systems the selection of an optimal spectrum is a key issue. METHODS:
We investigated different anode/filter (A/F) combinations over the clinical range
of tube voltages. The figure-of-merit (FOM) to be optimized was squared signal
difference-to-noise ratio divided by glandular dose. Measurements were performed
on a Siemens Mammomat 3000 with a Fuji Profect reader (SiFu) and on a GE
Senograph DMR with a Carestream reader (GECa). RESULTS: For 50mm PMMA the maximum
FOM was found with a Mo/Rh spectrum between 27kVp and 29kVp, while with 60mm
Mo/Rh at 28kVp (GECa) and W/Rh 25kVp (SiFu) were superior. For 70mm PMMA the
Rh/Rh spectrum had a peak at about 31kVp (GECa). FOM increases from 10% to >100%
are demonstrated. CONCLUSION: Optimization as proposed in this paper can either
lead to dose reduction with comparable image quality or image quality improvement
if necessary. For systems with limited A/F combinations the choice of tube
voltage is of considerable importance. In this work, optimization of AEC
parameters such as anode-filter combination and tube potential was demonstrated
for mammographic CR systems.
PMID- 27496198
TI - Hepatitis E virus in acute liver failure: An unusual suspect?
PMID- 27496199
TI - Foot contact dermatitis: nitrofurazone as the main cause in a retrospective,
cross-sectional study over a 16-year period from Turkey.
AB - BACKGROUND: The major causative agents in allergic contact dermatitis of the foot
may differ from country to country. Sufficient data on foot eczema in patients
from Turkey are lacking. OBJECTIVE: To identify the clinically relevant contact
allergens in foot eczema and determine the role of patch test series and
patients' own materials in the detection of the responsible allergens. METHODS:
Among 1753 patients patch tested between 1996 and 2012 in our clinic, 53 with
suspected allergic foot eczema were enrolled in this retrospective, cross
sectional study. Forty nine patients were patch tested with the extended European
baseline series, 49 with supplemental series including rubber, leather, topical
drugs, textile, cosmetic series containing preservatives and emulgators and
varnish/plastic/glue series, and 37 with their own substances. RESULTS: Thirty of
the 53 patch tested patients showing sensitization to at least one clinically
relevant allergen were diagnosed with allergic foot eczema. The main eliciting
agent was nitrofurazone (n = 8), followed by leather shoe allergens, ie,
potassium dichromate (n = 6), p-tert-butylphenol formaldehyde resin and
formaldehyde, in the second range. Rubber shoe allergens were less frequently
observed (n = 3). In more than 1/3 of the patients, the causative agent could
only be identified by testing the patient's own substances and/or supplemental
series. CONCLUSION: Nitrofurazone was the leading causative agent followed by
leather shoe allergens. Pediatric patients were frequently sensitized with shoe
allergens. Patch testing with patient's own substances had a critical value in
the detection of the causative agent in a significant number of patients.
PMID- 27496200
TI - Occurrence and outcome of de novo metastatic breast cancer by subtype in a large,
diverse population.
AB - PURPOSE: To examine the occurrence and outcomes of de novo metastatic (Stage IV)
breast cancer, particularly with respect to tumor HER2 expression. METHODS: We
studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January
2005 to 31 December 2011 and reported to the California Cancer Registry.
Molecular subtypes were classified according to HER2 and hormone receptor (HR,
including estrogen and/or progesterone receptor) expression. Multivariable
logistic regression was used to estimate odds ratios (ORs) and 95 % confidence
intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional
hazards regression was used to assess relative hazard (RH) of mortality. RESULTS:
Five percent of invasive breast cancer was metastatic at diagnosis. Compared to
patients with earlier stage disease, patients with de novo metastatic disease
were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI
1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival
improved over time, but varied substantially across race/ethnicity (Asians: 34
months; African Americans: 6 months), neighborhood socioeconomic status (SES)
(highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45
months; triple negative: 12 months). In a multivariable model, triple negative
(RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had
worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2-
breast cancer. CONCLUSIONS: De novo metastatic breast cancer was more likely to
be HER2+. Among metastatic tumors, those that were HER2+ had better survival than
other subtypes.
PMID- 27496202
TI - Simple Preparation of Rhodococcus erythropolis DSM 44534 as Biocatalyst to
Oxidize Diols into the Optically Active Lactones.
AB - In the current study, we present a green toolbox to produce ecological compounds
like lactone moiety. Rhodococcus erythropolis DSM 44534 cells have been used to
oxidize both decane-1,4-diol () and decane-1,5-diol () into the corresponding
gamma- () and delta-decalactones () with yield of 80% and enantiomeric excess
(ee) = 75% and ee = 90%, respectively. Among oxidation of meso diols, (-)-(1S,5R)
cis-3-oxabicyclo[4.3.0]non-7-en-2-one (5a) with 56% yield and ee = 76% as well as
(-)-(2R,3S)-cis-endo-3-oxabicyclo[2.2.1]dec-7-en-2-one (6a) with 100% yield and
ee = 90% were formed. It is worth mentioning that R. erythropolis DSM 44534 grew
in a mineral medium containing ethanol as the sole source of energy and carbon
Chirality 28:623-627, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27496201
TI - Prevalence of adhesin and toxin genes in E. coli strains isolated from diarrheic
and non-diarrheic pigs from smallholder herds in northern and eastern Uganda.
AB - BACKGROUND: Enterotoxigenic E. coli (ETEC) significantly contribute to diarrhea
in piglets and weaners. The smallholder pig producers in Uganda identified
diarrhea as one of the major problems especially in piglets. The aim of this
study was to; i) characterize the virulence factors of E. coli strains isolated
from diarrheic and non-diarrheic suckling piglets and weaners from smallholder
herds in northern and eastern Uganda and ii) identify and describe the post
mortem picture of ETEC infection in severely diarrheic piglets. Rectal swab
samples were collected from 83 piglets and weaners in 20 herds and isolated E.
coli were characterized by PCR, serotyping and hemolysis. RESULTS: The E. coli
strains carried genes for the heat stable toxins STa, STb and EAST1 and adhesins
F4 and AIDA-I. The genes for the heat labile toxin LT and adhesins F5, F6, F18
and F41 were not detected in any of the E. coli isolates. Where the serogroup
could be identified, E. coli isolates from the same diarrheic pig belonged to the
same serogroup. The prevalence of EAST1, STb, Stx2e, STa, AIDA-I, and F4 in the
E. coli isolates from suckling piglets and weaners (diarrheic and non-diarrheic
combined) was 29, 26.5, 2.4, 1.2, 16, and 8.4 %, respectively. However the
prevalence of F4 and AIDA-I in E. coli from diarrheic suckling piglets alone was
22.2 and 20 %, respectively. There was no significant difference in the
prevalence of the individual virulence factors in E. coli from the diarrheic and
non-diarrheic pigs (p > 0.05). The main ETEC strains isolated from diarrheic and
non-diarrheic pigs included F4/STb/EAST1 (7.2 %), F4/STb (1.2 %), AIDA/STb/EAST1
(8 %) and AIDA/STb (8 %). At post-mortem, two diarrheic suckling piglets carrying
ETEC showed intact intestinal villi, enterocytes and brush border but with a
layer of cells attached to the brush border, suggestive of ETEC infections.
CONCLUSION: This study has shown that the F4 fimbriae is the most predominant in
E. coli from diarrheic piglets in the study area and therefore an F4-based
vaccine should be considered one of the preventive measures for controlling ETEC
infections in the piglets in northern and eastern Uganda.
PMID- 27496204
TI - Risk-induced neophobia: does sensory modality matter?
AB - Recent studies have documented that exposure to high levels of background risk
can induce neophobic predator avoidance in prey animals, whereby they respond to
any novel cue with an anti-predator response. Such phenotypically plastic
predator avoidance may allow prey to maximize anti-predator benefits in variable
risk environments. It remains poorly understood whether risk assessment
information from different sensory modalities can be integrated to induce
generalized, cross-sensory system neophobic responses. Here, we directly test
this hypothesis by exposing juvenile convict cichlids (Amatitlania nigrofasciata)
to high- versus low-risk environments using either conspecific alarm cue
(chemosensory risk) or a model avian predator (visual/mechanical risk) and
testing their response to a novel chemosensory cue (Experiment 1) or visual cue
(Experiment 2). Our results suggest that regardless of the sensory modality used
to increased perceived risk, cichlids pre-exposed to high-risk conditions
exhibited increased predator avoidance in response to any novel visual or
chemical cue. As expected, cichlids pre-exposed to low-risk conditions did not
display any neophobic responses. Our results suggest that induced neophobia is
not cue specific; rather, it may function as a generalized response to perceived
predation risk.
PMID- 27496203
TI - Hypoxia exposure and B-type natriuretic peptide release from Langendorff heart of
rats.
AB - AIM: We studied whether available oxygen without induced mechanical stretch
regulates the release of the biologically active B-type natriuretic peptide (BNP)
from Langendorff heart. METHODS: Rat hearts were isolated and perfused with a
physiological Krebs-Henseleit solution at a constant hydrostatic pressure in
Langendorff set-up. The basal O2 level of perfusate (24.4 +/- 0.04 mg L-1 ) was
gradually lowered to 3.0 +/- 0.01 mg L-1 over 20 min using N2 gas (n = 7). BNP
and O2 level were measured from coronary flow. During control perfusions (n = 5),
the O2 concentration was kept at 26.6 +/- 0.3 mg L-1 . RESULTS: A low oxygen
concentration in the perfusate was associated with a significant increase in BNP
release (F = 40.4, P < 0.001). Heart rate decreased when the oxygen concentration
in the perfusate reached 9.1 +/- 0.02 mg L-1 and continued to fall in lower
oxygen concentrations (F = 14.8, P < 0.001). There was also a significant but
inverse correlation between BNP and oxygen in the coronary flow (R2 = 0.27, P <
0.001). CONCLUSION: In the spontaneously beating Langendorff rat heart, a
decreasing concentration of oxygen in the ingoing perfusion increased the
secretion of BNP. The effect of oxygen was independent of mechanical stretch of
the heart as it occurred even when the heart rate decreased but the pressure
conditions remained constant. The difference in the oxygen capacitance of blood
and Krebs-Henseleit solution appears to be a major factor affecting secretion of
BNP, which is correlated with the oxygen tension of myocardial cells and affected
both by the oxygen concentration and capacitance of solution perfusing the heart
and by the coronary flow.
PMID- 27496205
TI - Harbour seals (Phoca vitulina) are able to time precisely.
AB - Time along with space is one of the two fundamental dimensions of life. Whereas
spatial aspects have been considered in experiments with marine mammals, research
has so far not focused on timing per se although it is most likely involved in
many behaviours such as foraging or navigation. This study investigated whether
harbour seals possess a sense of time and how precisely they are able to
discriminate time intervals. Experiments took place in a chamber that allowed
keeping ambient illumination constant at 40 lx. The animal was presented with a
white circle on a black background on a monitor displayed for a preset time
interval. In a two-alternative forced-choice experiment, the animal had to
indicate the presence of the standard or a longer comparison time interval by
moving its head to one out of two response targets. Time difference thresholds
were assessed for various standard intervals between 3 to 30 s adopting a
staircase procedure. The experimental animal found access to the task easily and
discriminated time intervals with difference thresholds partly in the millisecond
range. Thus our study revealed a well-developed sense of time in a pinniped
species. Time, besides information provided by the classical senses, is thus most
likely an important parameter seals can rely on for various tasks including
navigation and foraging.
PMID- 27496206
TI - An in silico study of the effect of SOD1 electrostatic loop dynamics on amyloid
like filament formation.
AB - Superoxide dismutase [Cu-Zn], or SOD1, is a homo-dimeric protein that functions
as an antioxidant by scavenging for superoxides. A wide range of SOD1 variants
are linked to inherited, or familial, amyotrophic lateral sclerosis, a
progressive and fatal neurodegenerative disease. Aberrant SOD1 oligomerization
has been strongly implicated in disease causation, even for sporadic ALS, or
SALS, which accounts for ~90 % of ALS cases. Small heat shock proteins (sHSP)
have been shown to protect against amyloid fibril formation in vitro, and the
sHSP alphaB-crystallin suppresses in vitro aggregation of SOD1. We are seeking to
elucidate the structural features of both SOD1 amyloid formation and alphaB
crystallin amyloid suppression. Specifically, we have used a flexible docking
protocol to refine our model of a SOD1 non-obligate tetramer, postulated to
function as a transient desolvating complex. Homology modeling and molecular
dynamics (MD) are used to supply the missing structural elements of a previously
characterized SOD1 amyloid filament, thereby providing a structural analysis for
the observed gain of interaction. This completed filament is then further
modified using MD to provide a structural model for protofibril capping of SOD1
filaments by alphaB-crystallin.
PMID- 27496207
TI - Extended lateral thoracic fasciocutaneous biosynthetic flap for reconstruction of
full-thickness partial external ear defects: an experimental study.
AB - External ear reconstruction is a controversial topic in reconstructive plastic
surgery. Here, we prepared a pedicled biosynthetic flap for full-thickness,
partial ear defects in rabbits. We operated on six adult female New Zealand
rabbits weighing 3-4 kg. The dimensions of the lateral thoracic fasciocutaneous
flap were 7 * 6 cm. The flap was elevated based on one of the bilaterally located
internal thoracic arteries, which were dissected proximally. The pedicled flap
was folded in two, and polypropylene mesh was sandwiched in the middle. The flap
was adapted to a defect of 3.5 * 3 cm in diameter. In fact, the defect was
created before elevation of the flap. Rabbits were followed up for 4 weeks, at
the end of which they were killed and their ears were evaluated
histopathologically. The survival rate of the rabbits was 100 %. All pedicled
biosynthetic flaps were viable, but one showed partial (20 %) necrosis (1/6) and
one was partially detached (1/6). Macroscopic (color, thickness, texture) and
histological (polymorphonuclear leukocyte invasion in the skin, subcutaneous
tissue, and at the junction between the polypropylene mesh and the flap) features
of the flap were compared to the ipsilateral ear. A new technique was developed
for partial external ear reconstruction with sufficient inner skeletal support
and outer skin lining. Level of evidence Level NA.
PMID- 27496208
TI - Polypropylene mesh for nasal septal perforation repair: an experimental study.
AB - The aim of this study is to determine the effectiveness and biocompatibility of
polypropylene mesh for the repair of nasal septal perforations in an animal model
on rabbits. A full-thickness nasal septal perforation with a diameter of nearly
10 * 10 mm was created on 12 rabbits, and then the perforation was reconstructed
with two different methods. We used mucosal flaps and polypropylene mesh as an
interpositional graft in group 1. Only mucosal flaps were used for reconstruction
and are identified as group 2. After 4 weeks, we removed the nasal septum of the
rabbits and performed histopathological examinations for acute rejection,
infection, inflammatory response, fibrosis, and granuloma formation. We found
perforation closure rates of 75 and 25 % in groups 1 and 2, respectively.
Inflammatory response was seen in all specimens of group 1 (100 %). The
inflammatory response was +1 in five of the specimens (62.5 %), +2 in one
specimen (12.5 %), and +3 in two specimens (25 %). Mild fibrosis around the mesh
was detected in four specimens (50 %), medium-level fibrosis was detected in one
(12.5 %), and no fibrosis was detected in three (37.5 %). Severe fibrosis was not
seen in any specimens. The foreign-body reaction was limited to a few giant
cells, and granuloma formation was seen in two specimens (25 %). The propylene
mesh showed excellent biocompatibility with the septal mucosa, and it can,
therefore, be used for the repair of septal perforation as an interpositional
graft safely.
PMID- 27496209
TI - Transaxillary gasless endoscopic thyroidectomy versus conventional open
thyroidectomy: a randomized study.
AB - The objective of this study is to compare the outcomes of transaxillary gasless
endoscopic thyroidectomy (TGET) and conventional open thyroidectomy (COT). Thirty
three patients with thyroid nodule were enrolled. All patients were randomized
into two different groups. Sixteen patients underwent TGET and 17 patients
underwent COT. We analyzed the patients' characteristics, wound satisfaction, the
intraoperative phase, hospitalization, pain, and costs. The operative time for
the TGET group was significantly longer than in the COT group. The estimated
blood loss, the hospitalized days, and pain between the two groups were not
significantly different. The drainage content was significantly more in the TGET
group. The patients' wound satisfaction and mean total cost per case were
significantly greater in the TGET group. The TGET provided better cosmetic
outcomes and was comparable regarding the estimated blood loss, pain,
complication, and hospitalization. However, the TGET required a longer operative
time which determines the higher costs.
PMID- 27496210
TI - MicroRNA Regulators of Anxiety and Metabolic Disorders.
AB - Anxiety-related and metabolic disorders are under intense research focus. Anxiety
induced microRNAs (miRNAs) are emerging as regulators that are not only capable
of suppressing inflammation but can also induce metabolic syndrome-related
processes. We summarize here evidence linking miRNA pathways which share
regulatory networks in metabolic and anxiety-related conditions. In particular,
miRNAs involved in these disorders include regulators of acetylcholine signaling
in the nervous system and their accompanying molecular machinery. These have been
associated with anxiety-prone states in individuals, while also acting as
inflammatory suppressors. In peripheral tissues, altered miRNA pathways can lead
to dysregulated metabolism. Common pathways in metabolic and anxiety-related
phenomena might offer an opportunity to reclassify 'healthy' and 'unhealthy', as
well as metabolic and anxiety-prone biological states, and inform putative
strategies to treat these disorders.
PMID- 27496211
TI - Oxazolidinone-based allosteric modulators of mGluR5: Defining molecular switches
to create a pharmacological tool box.
AB - Herein we describe the structure activity relationships uncovered in the pursuit
of an mGluR5 positive allosteric modulator (PAM) for the treatment of
schizophrenia. It was discovered that certain modifications of an oxazolidinone
based chemotype afforded predictable changes in the pharmacological profile to
give analogs with a wide range of functional activities. The discovery of potent
silent allosteric modulators (SAMs) allowed interrogation of the mechanism-based
liabilities associated with mGluR5 activation and drove our medicinal chemistry
effort toward the discovery of low efficacy (fold shift) PAMs devoid of agonist
activity. This work resulted in the identification of dipyridyl 22 (BMS-952048),
a compound with a favorable free fraction, efficacy in a rodent-based cognition
model, and low potential for convulsions in mouse.
PMID- 27496212
TI - Synthesis and biological evaluation of some novel triazole hybrids of curcumin
mimics and their selective anticancer activity against breast and prostate cancer
cell lines.
AB - The anti-cancer property of curcumin, an active component of turmeric, is limited
due to its poor solubility, stability and bioavailability. To enhance its
efficacy, we designed a novel series of twenty-four monocarbonyl curcumin
analogue-1,2,3-triazole conjugates and evaluated their anti-cancer activity
towards endocrine related cancers. The new compounds (17-40) were synthesized
through CuAAC click reaction and SAR analysis carried out. Out of these all,
compound 17 showed most significant anti-cancer activity against prostate cancer
cells with IC50 values of 8.8MUM and 9.5MUM in PC-3 and DU-145 cells,
respectively. Another compound 26 showed significant anti-cancer activity against
breast cancer cells with IC50 of 6MUM, 10MUM and 6.4MUM in MCF-7, MDA-MB-231 and
4T1 cells, respectively while maintaining low toxicity towards non-cancer
originated cell line, HEK-293. Compounds 17 and 26 arrested cell cycle and
induced mitochondria-mediated apoptosis in cancer cells. Further, both of these
compounds significantly down-regulated cell proliferation marker (PCNA),
inhibited activation of cell survival protein (Akt phosphorylation), upregulated
pro-apoptotic protein (Bax) and down-regulated anti-apoptotic protein (Bcl-2) in
their respective cell lines. In addition, in vitro stability, solubility and
plasma binding studies of the compounds 17 and 26 showed them to be metabolically
stable. Thus, this study identified two new curcumin monocarbonyl-1,2,3-triazole
conjugate compounds with more potent activity than curcumin against breast and
prostate cancers.
PMID- 27496213
TI - Charting the chemical space around the (iso)indoline scaffold, a comprehensive
approach towards multitarget directed ligands.
AB - Within the framework of orthosteric G protein coupled receptor (GPCR)
polypharmacology herein we report the systematic elaboration and thorough
evaluation of a data matrix generated by sampling the chemical space around a
common 5,6-fused bicyclic heteroaromatic template applying characteristic
pharmacophore elements of central nervous system (CNS) relevant aminergic GPCR
ligands.
PMID- 27496214
TI - Quantitation of Human Cells that Produce Neutrophils and Platelets in Vivo
Obtained from Normal Donors Treated with Granulocyte Colony-Stimulating Factor
and/or Plerixafor.
AB - Plerixafor (P) together with granulocyte colony-stimulating factor (G) is now
recognized as an important strategy for mobilizing hematopoietic cells for use in
patients given myelosuppressive therapies. However, quantitative comparisons of
their ability to mobilize human cells with different hematopoietic activities in
vitro or in vivo (in immunodeficient mice) and their interrelationships have not
been investigated. To address these questions, we collected samples from 5 normal
adult volunteers before and after administering P alone and from another 5 before
and after a 4-day course of G and again after a subsequent injection of P.
Measurements of their blood content of CD34+ cells, in vitro myeloid colony
forming cells, 3- and 6-week long-term culture (LTC) cell outputs, and levels of
circulating human platelets, as well as myeloid and lymphoid cells obtained in
immunodeficient mice that received transplants, showed all activities were
maximal 4 hours after P preceded by G, and 3-week LTC outputs showed the highest
concordance with the 3-week circulating human neutrophil levels obtained in mice
that received transplants. Thus, human cells capable of producing neutrophils
rapidly in vivo were optimally mobilized by the G + P protocol, and the 3-week
LTC assay appears to offer a more specific predictor of their levels than
conventional CD34+ cell or colony-forming cell counts.
PMID- 27496216
TI - HapLogic: A Predictive Human Leukocyte Antigen-Matching Algorithm to Enhance
Rapid Identification of the Optimal Unrelated Hematopoietic Stem Cell Sources for
Transplantation.
AB - The search for a suitable human leukocyte antigen (HLA)-matched unrelated adult
stem cell donor (URD) or umbilical cord blood unit (UCB) is a complex process.
The National Marrow Donor Program (NMDP) developed a search algorithm known as
HapLogic, which is currently provided within the NMDP Traxis application. The
HapLogic algorithm has been in use since 2006 and has advanced URD/UCB HLA
matching technology. The algorithm has been shown to have high predictive
accuracy, which can streamline URD/UCB selection and drive efficiencies in the
search process to the benefit of the stem cell transplantation community. Here,
we describe the fundamental components of the NMDP matching algorithm, output,
validation, and future directions.
PMID- 27496217
TI - Impact of Graft-Recipient ABO Compatibility on Outcomes after Umbilical Cord
Blood Transplant for Nonmalignant Disease.
AB - Existing literature shows mixed conclusions regarding the impact of ABO
incompatibility on outcomes after hematopoietic stem cell transplantation.
Because the future for umbilical cord blood (UCB) expansion technologies is
bright, we assessed whether this typically overlooked graft characteristic
impacted various outcomes after UCB transplantation (UCBT) for nonmalignant
disorders (NMDs). A prospectively maintained institutional blood and marrow
transplant program database was queried for all patients undergoing first UCBT
for NMDs. UCB and recipient ABO compatibility was considered as matched, major
mismatched, minor mismatched, or bidirectional mismatched. The impact of ABO
incompatibility was assessed on overall survival, graft failure, acute and
chronic graft-versus-host disease (GVHD), time to neutrophil and platelet
recovery, day 0 to day 100 RBC transfusion burden, and donor hematopoietic
chimerism. Through December 2014, 270 patients have undergone first UCBT for
various NMDs. In both univariable and multivariable analyses, ABO compatibility
status did not appear to impact any outcomes assessed, although a trend toward
increased grades III to IV acute GVHD was seen in recipients of major mismatched
units. When considering UCBT for treatment of NMDs, ABO compatibility between the
donor unit and intended recipient does not appear to be an important
consideration in the UCB unit choice.
PMID- 27496215
TI - Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple
Myeloma: A CIBMTR Analysis.
AB - Conventional cytogenetics and interphase fluorescence in situ hybridization
(FISH) identify high-risk multiple myeloma (HRM) populations characterized by
poor outcomes. We analyzed these differences among HRM versus non-HRM populations
after upfront autologous hematopoietic cell transplantation (autoHCT). Between
2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or
cytogenetic data with upfront autoHCT were identified in the Center for
International Blood and Marrow Transplant Research database. HRM was defined as
del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or
chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM
patients (17.5%), induction with bortezomib and immunomodulatory agents (imids)
was higher compared with non-HRM (56% versus 43%, P < .001) with similar
pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100
post-transplant, at least a very good partial response was 59% in HRM and 61% in
non-HRM (P = .6). More HRM patients received post-transplant therapy with
bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant
progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were
37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3
years, PFS for HRM patients with and without post-transplant therapy was 46% (95%
confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM
patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus
39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post
transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65)
compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM
patients with and without post-transplant therapy, respectively. Among patients
receiving post-transplant therapy, there was no difference in OS between HRM and
non-HRM (P = .08). In addition to HRM, higher stage, less than a CR
pretransplant, lack of post-transplant therapy, and African American race were
associated with worse OS. In conclusion, we show HRM patients achieve similar day
100 post-transplant responses compared with non-HRM patients, but these responses
are not sustained. Post-transplant therapy appeared to improve the poor outcomes
of HRM.
PMID- 27496218
TI - High Variability in the Reported Management of Hepatic Veno-Occlusive Disease in
Children after Hematopoietic Stem Cell Transplantation.
AB - Veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic
stem cell transplantation (HSCT). Patients with VOD are often critically ill and
require close collaboration between transplant physicians and intensivists. We
surveyed members of a consortium of pediatric intensive care unit (PICU) and
transplant physicians to assess variability in the self-reported approach to the
diagnosis and management of VOD. An internet-based self-administered survey was
sent to pediatric HSCT and PICU providers from September 2014 to February 2015.
The survey contained questions relating to the diagnosis and treatment of VOD.
The response rate was 41% of 382 providers surveyed. We found significant
variability in the diagnostic and management approaches to VOD in children. Even
though ultrasound is not part of the diagnostic criteria, providers reported
using reversal of portal venous flow seen on abdominal ultrasound in addition to
Seattle criteria (70%) or Baltimore criteria to make the diagnosis of VOD. Almost
40% of respondents did not diagnose VOD in anicteric patients (bilirubin < 2
mg/dL). Most providers (75%) initiated treatment with defibrotide at the time of
diagnosis, but 14%, 7%, and 6% of the providers waited for reversal of portal
venous flow, renal dysfunction, or pulmonary dysfunction, respectively, to
develop before initiating therapy. Only 50% of the providers restricted fluids to
75% of the daily maintenance, whereas 21% did not restrict fluids at all. Albumin
with diuretics was used by 95% of respondents. Platelets counts were maintained
at 20,000 to 50,000/mm(3) and 10,000 to 20,000/mm(3) by 64% and 20% of the
respondents, respectively. Paracentesis was generally initiated in the setting of
oliguria or hypoxia, and nearly 50% of the providers used continuous drainage to
gravity, whereas the remainder used an intermittent drainage approach. Nearly 73%
of the transplant providers used VOD prophylaxis, whereas the remainder did not
use any medications for VOD prophylaxis. There was also considerable variation in
the management strategies among the transplant and critical care providers. We
conclude that there is considerable self-reported variability in the diagnosis
and management of VOD in children. The practice variations reported in this study
should encourage the development of standard practice guidelines, which will be
helpful in improving the outcome of this potentially fatal complication.
PMID- 27496219
TI - Meta-analysis looks at effectiveness of MoodGYM programme in computerised
cognitive behavioural therapy.
PMID- 27496220
TI - Linear mass scans in quadrupole ion traps using the inverse Mathieu q scan.
AB - RATIONALE: Secular frequency scanning is a method of mass selectively scanning
ions out of a quadrupole ion trap by linearly ramping the frequency of the
resonance ejection signal through ion secular frequencies at constant rf
amplitude and frequency. The method is electronically much simpler than resonance
ejection but it requires a complex nonlinear calibration procedure to correlate
mass-to-charge with time. METHODS: A method of secular frequency scanning in
quadrupole ion traps is described in which mass-to-charge is linear with time.
This method, termed an "inverse Mathieu q scan", contrasts with linear frequency
sweeping which requires a complex nonlinear mass calibration procedure. In the
current method, mass scans are forced to be linear with time by scanning the
frequency of the supplementary ac so that there is an inverse relationship
between the ejected ion's Mathieu q parameter and time. RESULTS: In all cases,
excellent mass spectral linearity is observed. The rf amplitude is shown to
control both the scan range and the scan rate, whereas the ac amplitude and scan
rate influence the mass resolution. The scan rate depends linearly on the rf
amplitude, a unique feature of this scan. Although changes in either rf or ac
amplitude affect the positions of peaks in time, they do not change the mass
calibration procedure since this only requires a simple linear fit of m/z vs
time. Space charge effects are shown to give rise to significant changes in
resolution as well as to mass shifts. CONCLUSIONS: A method of secular frequency
scanning which provides a linear mass scale has been demonstrated. The inverse
Mathieu q scan offers a significant increase in mass range and power savings
while maintaining access to linearity, paving the way for a mass spectrometer
based completely on ac waveforms for ion isolation, ion activation, and ion
ejection. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27496221
TI - Albuminuria is not associated with elevated urinary vesicle concentration but can
confound nanoparticle tracking analysis.
AB - AIM: Extracellular vesicles, such as exosomes, are present in urine with reports
of roles in intercellular signalling and diagnostic utility. However, the extent
to which the concentration and characteristics of urinary vesicles are altered in
albuminuric renal disease has not been well characterized. In this study, we
examined the number and characteristics of extracellular vesicles in albuminuric
urine. METHODS: Vesicles were isolated from the urine of 32 patients with varying
levels of albuminuria using ultracentrifugation and density gradient purification
and were examined using nanoparticle tracking analysis, immunoblotting and
transmission electron microscopy. The size profile of particles in these urine
preparations was compared with albumin-containing solutions. RESULTS: Overall,
there were no substantial differences in the number, or characteristics, of
vesicles released into proteinuric urine. Analysis of albumin-containing
solutions showed particles of exosome-like size, suggesting that such particles
can mimic exosomes in standard nanoparticle tracking analysis. Albumin and IgG
depletion of proteinuric urine resulted in a substantial reduction in the
concentration of particles detected by nanoparticle tracking analysis.
CONCLUSION: There was no increase in urinary vesicle concentration in patients
with albuminuria. Furthermore, these results demonstrate the need for cautious
interpretation of nanoparticle tracking analysis of vesicle concentration in
biological fluids containing protein and for sophisticated preparative methods in
vesicle purification from urine.
PMID- 27496223
TI - Impact of orthognathic surgery on oral health-related quality of life in patients
with jaw deformities.
AB - The purpose of this study was to clarify the impact of orthognathic surgery on
oral health-related quality of life (OHRQOL) in patients with jaw deformities.
The subjects were 65 patients (21 males and 44 females) who underwent
orthognathic surgery. The mean age of the patients was 23.6 years. Forty-seven
patients had skeletal class III malocclusions, eight patients had skeletal class
II, and 10 patients had skeletal class I with facial asymmetry and/or open bite.
OHRQOL was assessed using the Japanese version of the Oral Health Impact Profile
(OHIP-J54) before and 6 months after surgery. While OHIP-J54 scores in the
patients before surgery were significantly higher than those in the control
subjects, OHIP-J54 scores after surgery were significantly lower than those
before surgery. OHIP-J54 scores in older patients were significantly higher than
those in younger patients. In conclusion, most patients with jaw deformities have
lower OHRQOL than individuals with normal occlusion, and orthognathic surgery has
a positive impact on OHRQOL. The determination of OHRQOL in patients with jaw
deformities seems to be very useful for understanding the patients' problems and
for assessing the extent of changes in terms of patient well-being.
PMID- 27496222
TI - Disrupted cooperation between transcription factors across diverse cancer types.
AB - BACKGROUND: Transcription Factors (TFs), essential for many cellular processes,
generally work coordinately to induce transcriptional change in response to
internal and external signals. Disrupted cooperation between TFs, leading to
dysregulation of target genes, contributes to the pathogenesis of many diseases,
including cancer. Although the aberrant activation of individual TFs and the
functional effects have been widely studied, the perturbation of TF cooperativity
in cancer has rarely been explored. RESULTS: We used TF co-expression as proxy as
cooperativity and performed a large-scale study on disrupted TF cooperation
across seven cancer types. While the connectivity of downstream effectors, like
metabolic genes and TF targets, were more or similarly disrupted than/with non
TFs, the cooperativity of TFs (upstream regulators) were consistently less
disturbed in all studied cancer types. Highly coordinated TFs in normal, however,
generally lost that cooperation in cancer. Although different types of cancer
shared very few TF pairs with highly disrupted cooperation, the cooperativity of
interferon regulatory factors (IRF) was highly disrupted in six cancer types.
Specifically, the cooperativity of IRF8 was highly perturbed in lung cancer,
which was further validated by two independent lung squamous cell carcinoma
(LUSC) and lung adenocarcinoma (LUAD) datasets. More interestingly, the
cooperativity of IRF8 was markedly associated with tumor progression and even
contributed to the patient survival independent of tumor stage. CONCLUSIONS: Our
findings underscore the far more important role of TF cooperativity in
tumorigenesis than previously appreciated. Disrupted cooperation of TFs provides
potential clinical utility as prognostic markers for predicting the patient
survival.
PMID- 27496224
TI - Decreased basal insulin secretion from pancreatic islets of pups in a rat model
of maternal obesity.
AB - Maternal obesity (MO) is a deleterious condition that enhances susceptibility of
adult offspring to metabolic diseases such as type 2 diabetes. The objective is
to study the effect of MO on in vitro insulin secretion and pancreatic cellular
population in offspring. We hypothesize that a harmful antenatal metabolic
environment due to MO diminishes the basal glucose-responsive secretory function
of pancreatic beta cells in offspring. Mothers were fed a control (C) or high-fat
diet from weaning through pregnancy (120 days) and lactation. At postnatal days
(PNDs) 36 and 110, pups were killed, peripheral blood was collected and
pancreatic islets were isolated. Basal insulin secretion was measured in vitro in
islets for 60 min. It was found that blood insulin, glucose and homeostasis model
assessment (HOMA) index were unaffected by maternal diet and age in females.
However, male MO offspring at PND 110 showed hyperinsulinemia and insulin
resistance compared with C. Body weight was not modified by MO, but fat content
was higher in MO pups compared with C pups. Triglycerides and leptin
concentrations were higher in MO than in C offspring in all groups except in
females at PND 36. Pancreatic islet cytoarchitecture was unaffected by MO. At PND
36, islets of male and female C and MO offspring responded similarly to glucose,
but at PND 110, male and female MO offspring islets showed a 50% decrease in
insulin secretion. It was concluded that MO impairs basal insulin secretion of
offspring with a greater impact on males than females, and this effect mainly
manifests in adulthood.
PMID- 27496225
TI - Disparity in maternal, newborn and child health services in high focus states in
India: a district-level cross-sectional analysis.
AB - OBJECTIVES: To examine the level and trend in the coverage gap of a set of
interventions of maternal and child health services using a summary index and to
assess the disparity in usage of maternal and child health services in the
districts of high focus states of India. DESIGN: Data for the present study are
taken from the Annual Health Survey (AHS), 2010-2013 and Census of India, 2011.
SETTINGS: This study used secondary data from states having higher mortality and
fertility rates, termed as high focus states in India. PARTICIPANTS: District
level information regarding children aged 12-23 months and ever married women
aged 15-49 years has been extracted from the AHS (2010-2013), and household
amenities, female literacy and main workforce information has been obtained from
the Census of India 2011. MEASURES: 2 summary indexes were calculated first for
maternal and child health services and another for socioeconomic and development
status, using data from AHS and Census. Cronbach's alpha was used to assess the
internal consistency of the items used in the index. RESULTS: The result shows
that the coverage gap is highest in Uttar Pradesh (37%) and lowest in Madhya
Pradesh (21%). Converge gap and socioeconomic development are negatively
correlated (r=-0.49, p=0.01). The average coverage gap was highest in the lowest
quintile of socioeconomic development. There was an absolute change of 1.5% per
year in coverage gap during 2009-2013. In regression analysis, the coefficient of
determination was 0.24, beta=-30.05, p=0.01 for a negative relationship between
socioeconomic development and coverage gap. CONCLUSIONS: There is a significant
disparity in the usage of maternal and child healthcare services in the districts
of India. Resource-rich people (urban residents and richest quintile) are way
ahead of marginalised people (rural residents and poorest quintile) in the usage
of healthcare services.
PMID- 27496226
TI - Systematic review of validated case definitions for diabetes in ICD-9-coded and
ICD-10-coded data in adult populations.
AB - OBJECTIVES: With steady increases in 'big data' and data analytics over the past
two decades, administrative health databases have become more accessible and are
now used regularly for diabetes surveillance. The objective of this study is to
systematically review validated International Classification of Diseases (ICD)
based case definitions for diabetes in the adult population. SETTING,
PARTICIPANTS AND OUTCOME MEASURES: Electronic databases, MEDLINE and Embase, were
searched for validation studies where an administrative case definition (using
ICD codes) for diabetes in adults was validated against a reference and
statistical measures of the performance reported. RESULTS: The search yielded
2895 abstracts, and of the 193 potentially relevant studies, 16 met criteria.
Diabetes definition for adults varied by data source, including physician claims
(sensitivity ranged from 26.9% to 97%, specificity ranged from 94.3% to 99.4%,
positive predictive value (PPV) ranged from 71.4% to 96.2%, negative predictive
value (NPV) ranged from 95% to 99.6% and kappa ranged from 0.8 to 0.9), hospital
discharge data (sensitivity ranged from 59.1% to 92.6%, specificity ranged from
95.5% to 99%, PPV ranged from 62.5% to 96%, NPV ranged from 90.8% to 99% and
kappa ranged from 0.6 to 0.9) and a combination of both (sensitivity ranged from
57% to 95.6%, specificity ranged from 88% to 98.5%, PPV ranged from 54% to 80%,
NPV ranged from 98% to 99.6% and kappa ranged from 0.7 to 0.8). CONCLUSIONS:
Overall, administrative health databases are useful for undertaking diabetes
surveillance, but an awareness of the variation in performance being affected by
case definition is essential. The performance characteristics of these case
definitions depend on the variations in the definition of primary diagnosis in
ICD-coded discharge data and/or the methodology adopted by the healthcare
facility to extract information from patient records.
PMID- 27496227
TI - Usage, adherence and attrition: how new mothers engage with a nurse-moderated web
based intervention to support maternal and infant health. A 9-month observational
study.
AB - OBJECTIVES: To identify factors predicting use, adherence and attrition with a
nurse-moderated web-based group intervention designed to support mothers of
infants aged 0-6 months. DESIGN: 9-Month observational study. SETTING: Community
maternal and child health service. PARTICIPANTS: 240 mothers attending initial
postnatal health checks at community clinics who were randomly assigned to the
intervention arm of a pragmatic preference randomised trial (total randomised
controlled trial, n=819; response rate=45%). INTERVENTION: In the first week
(phase I), mothers were assisted with their first website login by a research
assistant. In weeks 2-7 (phase II), mothers participated in the web-based
intervention with an expectation of weekly logins. The web-based intervention was
comparable to traditional face-to-face new mothers' groups. During weeks 8-26
(phase III), mothers participated in an extended programme at a frequency of
their choosing. PRIMARY OUTCOME MEASURES: Number of logins and posted messages.
Standard self-report measures assessed maternal demographic and psychosocial
characteristics. RESULTS: In phase II, the median number of logins was 9 logins
(IQR=1-25), and in phase III, it was 10 logins (IQR=0-39). Incident risk ratios
from multivariable analyses indicated that compared to mothers with the lowest
third of logins in phase I, those with the highest third had 6.43 times as many
logins in phase II and 7.14 times in phase III. Fifty per cent of mothers logged
in at least once every 30 days for 147 days after phase I and 44% logged-in at
least once in the last 30 days of the intervention. Frequency of logins during
phase I was a stronger predictor of mothers' level of engagement with the
intervention than their demographic and psychosocial characteristics.
CONCLUSIONS: Mothers' early use of web-based interventions could be employed to
customise engagement protocols to the circumstances of individual mothers with
the aim of improving adherence and reducing attrition with web-based
interventions. TRIAL REGISTRATION NUMBER: ACTRN12613000204741; Results.
PMID- 27496228
TI - Exploring unintended consequences of policy initiatives in mental health: the
example of Child and Adolescent Mental Health Services (CAMHS) in England.
AB - OBJECTIVES: The impact of policy and funding on Child and Adolescent Mental
Health Service (CAMHS) activity and capacity, from 2003 to 2012, was assessed.
The focus was on preschool children (aged 0-4 years), as current and 2003 policy
initiatives stressed the importance of 'early intervention'. SETTINGS: National
service capacity from English CAMHS mapping was obtained from 2003 to 2008
inclusive. English Hospital Episode Statistics (HES) for English CAMHS was
obtained from 2003 to 2012. The Child and Adolescent Faculty of the Royal College
of Psychiatrists surveyed its members about comparative 0-4-year service activity
and attitudes in 2012. PARTICIPANTS: CAMHS services in England provided HES and
CAMHS mapping data. The Child and Adolescent Faculty of the Royal College of
Psychiatrists are child psychiatrists, including trainees. OUTCOME MEASURES:
CAMHS mapping data provided national estimates of total numbers of CAMHS
patients, whereas HES data counted appointments or episodes of inpatient care.
The survey reported on Child Psychiatrists' informal estimates of service
activity and attitudes towards children aged 0-4 years. RESULTS: The association
between service capacity and service activity was moderated by an interaction
between specified funding and age, the youngest children benefiting least from
specified funding and suffering most when it was withdrawn (Pr=0.005). Policy
review and significant differences between age-specific HES trends (Pr<0.001)
suggested this reflected prioritisation of older children. Clinicians were
unaware of this effect at local level, though it significantly influenced their
attitudes to prioritising this group (Pr=0.02). CONCLUSIONS: If the new policy
initiative for CAMHS is to succeed, it will need to have time-limited priorities
attached to sustained, specified funding, with planning for limits as well as
expansion. Data collection for policy evaluation should include measures of
capacity and activity.
PMID- 27496229
TI - Semi-individualised Chinese medicine treatment as an adjuvant management for
diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open
label pragmatic clinical trial.
AB - INTRODUCTION: Diabetes mellitus and diabetic nephropathy (DN) are prevalent and
costly to manage. DN is the leading cause of end-stage kidney disease.
Conventional therapy blocking the renin-angiotensin system has only achieved
limited effect in preserving renal function. Recent observational data show that
the use of Chinese medicine (CM), a major form of traditional medicine used
extensively in Asia, could reduce the risk of end-stage kidney disease. However,
existing clinical practice guidelines are weakly evidence-based and the effect of
CM remains unclear. This trial explores the effect of an existing integrative
Chinese-Western medicine protocol for the management of DN. OBJECTIVE: To
optimise parameters and assess the feasibility for a subsequent phase III
randomised controlled trial through preliminary evaluation on the effect of an
adjuvant semi-individualised CM treatment protocol on patients with type 2
diabetes with stages 2-3 chronic kidney disease and macroalbuminuria. METHODS AND
ANALYSIS: This is an assessor-blind, add-on, randomised, controlled, parallel,
multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed
with DN will be recruited and randomised 1:1 to a 48-week additional semi
individualised CM treatment programme or standard medical care. Primary end
points are the changes in estimated glomerular filtration rate and spot urine
albumin-to-creatinine ratio between baseline and treatment end point. Secondary
end points include fasting blood glucose, glycated haemoglobin, brain natriuretic
peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary
monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor
beta1 and vascular endothelial growth factor. Adverse events are monitored
through self-completed questionnaire and clinical visits. Outcomes will be
analysed by regression models. Enrolment started in July 2015. ETHICS AND
REGISTRATION: This protocol is approved by the Institutional Review Board of the
University of Hong Kong/Hospital Authority Hong Kong West Cluster (reference
number UW 14-301). TRIAL REGISTRATION NUMBER: NCT02488252.
PMID- 27496230
TI - Hypertensive disorders of pregnancy and risk of diabetes in Indian women: a cross
sectional study.
AB - BACKGROUND: Epidemiological data from high-income countries suggest that women
with hypertensive disorders of pregnancy (HDP) are more likely to develop
diabetes later in life. OBJECTIVE: We investigated the association between pre
eclampsia and eclampsia (PE&E) during pregnancy and the risk of diabetes in
Indian women. DESIGN: Cross-sectional study. SETTING: India. METHODS: Data from
India's third National Family Health Survey (NFHS-3, 2005-2006), a cross
sectional survey of women aged 15-49 years, are used. Self-reported symptoms
suggestive of PE&E were obtained from 39 657 women who had a live birth in the 5
years preceding the survey. The association between PE&E and self-reported
diabetes status was assessed using multivariable logistic regression models
adjusting for dietary intake, body mass index (BMI), tobacco smoking, alcohol
drinking, frequency of TV watching, sociodemographic characteristics and
geographic region. RESULTS: The prevalence of symptoms suggestive of PE&E in
women with diabetes was 1.8% (n=207; 95% CI 1.5 to 2.0; p<0.0001) and 2.1% (n=85;
95% CI 1.8 to 2.3; p<0.0001), respectively, compared with 1.1% (n=304; 95% CI 1.0
to 1.4) and 1.2% (n=426; 95% CI 1.1 to 1.5) in women who did not report any PE&E
symptoms. In the multivariable analysis, PE&E was associated with 1.6 times
(OR=1.59; 95% CI 1.31 to 1.94; p<0.0001) and 1.4 times (OR=1.36; 95% CI 1.05 to
1.77; p=0.001) higher risk for self-reported diabetes even after controlling for
dietary intake, BMI and sociodemographic characteristics. CONCLUSIONS: HDP is
strongly associated with the risk of diabetes in a large nationally
representative sample of Indian women. These findings are important for a country
which is already tackling the burden of young onset of diabetes in the
population. However, longitudinal medical histories and a clinical measurement of
diabetes are needed in this low-resource setting.
PMID- 27496231
TI - Identification of adults with sepsis in the prehospital environment: a systematic
review.
AB - OBJECTIVE: Early identification of sepsis could enable prompt delivery of key
interventions such as fluid resuscitation and antibiotic administration which, in
turn, may lead to improved patient outcomes. Limited data indicate that
recognition of sepsis by paramedics is often poor. We systematically reviewed the
literature on prehospital sepsis screening tools to determine whether they
improved sepsis recognition. DESIGN: Systematic review. The electronic databases
MEDLINE, EMBASE, CINAHL, the Cochrane Library and PubMed were systematically
searched up to June 2015. In addition, subject experts were contacted. SETTING:
Prehospital/emergency medical services (EMS). STUDY SELECTION: All studies
addressing identification of sepsis (including severe sepsis and septic shock)
among adult patients managed by EMS. OUTCOME MEASURES: Recognition of sepsis by
EMS clinicians. RESULTS: Owing to considerable variation in the methodological
approach adopted and outcome measures reported, a narrative approach to data
synthesis was adopted. Three studies addressed development of prehospital sepsis
screening tools. Six studies addressed paramedic diagnosis of sepsis with or
without use of a prehospital sepsis screening tool. CONCLUSIONS: Recognition of
sepsis by ambulance clinicians is poor. The use of screening tools, based on the
Surviving Sepsis Campaign diagnostic criteria, improves prehospital sepsis
recognition. Screening tools derived from EMS data have been developed, but they
have not yet been validated in clinical practice. There is a need to undertake
validation studies to determine whether prehospital sepsis screening tools confer
any clinical benefit.
PMID- 27496233
TI - Patient safety priorities in mental healthcare in Switzerland: a modified Delphi
study.
AB - OBJECTIVE: Identifying patient safety priorities in mental healthcare is an
emerging issue. A variety of aspects of patient safety in medical care apply for
patient safety in mental care as well. However, specific aspects may be different
as a consequence of special characteristics of patients, setting and treatment.
The aim of the present study was to combine knowledge from the field and research
and bundle existing initiatives and projects to define patient safety priorities
in mental healthcare in Switzerland. The present study draws on national expert
panels, namely, round-table discussion and modified Delphi consensus method.
DESIGN: As preparation for the modified Delphi questionnaire, two round-table
discussions and one semistructured questionnaire were conducted. Preparative work
was conducted between May 2015 and October 2015. The modified Delphi was
conducted to gauge experts' opinion on priorities in patient safety in mental
healthcare in Switzerland. In two independent rating rounds, experts made private
ratings. The modified Delphi was conducted in winter 2015. RESULTS: Nine topics
were defined along the treatment pathway: diagnostic errors, non-drug treatment
errors, medication errors, errors related to coercive measures, errors related to
aggression management against self and others, errors in treatment of suicidal
patients, communication errors, errors at interfaces of care and structural
errors. CONCLUSIONS: Patient safety is considered as an important topic of
quality in mental healthcare among experts, but it has been seriously neglected
up until now. Activities in research and in practice are needed. Structural
errors and diagnostics were given highest priority. From the topics identified,
some are overlapping with important aspects of patient safety in medical care;
however, some core aspects are unique.
PMID- 27496232
TI - Design and rationale of a multicentre, randomised, double-blind, placebo
controlled clinical trial to evaluate the effect of vitamin D on ventricular
remodelling in patients with anterior myocardial infarction: the VITamin D in
Acute Myocardial Infarction (VITDAMI) trial.
AB - INTRODUCTION: Decreased plasma vitamin D (VD) levels are linked to cardiovascular
damage. However, clinical trials have not demonstrated a benefit of VD
supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute
myocardial infarction (STEMI) is the best human model to study the effect of
treatments on LV remodelling. We present a proof-of-concept study that aims to
investigate whether VD improves LV remodelling in patients with anterior STEMI.
METHODS AND ANALYSIS: The VITamin D in Acute Myocardial Infarction (VITDAMI)
trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144
patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg
capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months.
PRIMARY OBJECTIVE: to evaluate the effect of calcifediol on LV remodelling
defined as an increase in LV end-diastolic volume >=10% (MRI). SECONDARY
OBJECTIVES: change in LV end-diastolic and end-systolic volumes, ejection
fraction, LV mass, diastolic function, sphericity index and size of fibrotic
area; endothelial function; plasma levels of aminoterminal fragment of B-type
natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of
calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast
growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone
and phosphate). Differences in the effect of VD will be investigated according to
the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be
assessed. This is the first study to evaluate the effect of VD on cardiac
remodelling in patients with STEMI. ETHICS AND DISSEMINATION: This trial has been
approved by the corresponding Institutional Review Board (IRB) and National
Competent Authority (Agencia Espanola de Medicamentos y Productos Sanitarios
(AEMPS)). It will be conducted in accordance with good clinical practice
(International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP)) requirements,
ethical principles of the Declaration of Helsinki and national laws. The results
will be submitted to indexed medical journals and national and international
meetings. TRIAL REGISTRATION NUMBER: NCT02548364; Pre-results.
PMID- 27496234
TI - Combined cognitive-behavioural and mindfulness programme for people living with
dystonia: a proof-of-concept study.
AB - OBJECTIVES: To design and test the delivery of an intervention targeting the non
motor symptoms of dystonia and pilot key health and well-being questionnaires in
this population. DESIGN: A proof-of-concept study to test the delivery,
acceptability, relevance, structure and content for a 3-day group residential
programme for the management of dystonia. SETTING: Participants were recruited
from a single botulinum toxin clinic. The intervention was delivered in the
community. PARTICIPANTS: 14 participants consented to take part (2 withdrew prior
to the starting of intervention). The average age was 60 years (range 44-77), 8
of whom were female. After drop-out, 9 participants completed the 3-day
programme. INTERVENTION: A 3-day group residential programme. PRIMARY AND
SECONDARY OUTCOME MEASURES: Process evaluation and interviews were carried out
before and after the intervention to explore participant's views and
expectations, as well as experiences of the intervention. Select questionnaires
were completed at baseline, 1-month and 3-month follow-up. RESULTS: Although
participants were not sure what to expect from the programme, they found it
informative and for many this together with being in a group with other people
with dystonia legitimised their condition. Mindfulness was accepted and adopted
as a coping strategy. This was reflected in the 1-month follow-up. CONCLUSIONS:
We successfully delivered a 3-day residential programme to help those living with
dystonia manage their condition. Further improvements are suggested. The
quantitative outcome measures were acceptable to this group of patients with
dystonia.
PMID- 27496235
TI - Feasibility of repeated self-measurements of maximum step length and gait speed
by community-dwelling older persons.
AB - OBJECTIVES: Self-management of mobility and fall risk can be important in fall
prevention; however, it remains unstudied. Therefore, the current study assessed
whether community-dwelling older persons were able to repeatedly self-assess
maximum step length (MSL) and gait speed (GS) in their own home for a 6-month
period, how these tests changed during this period and if these changes were
related to falling. DESIGN: This is a prospective study. SETTING: This study was
conducted at home. PARTICIPANTS: A total of 56 community-dwelling older adults
(24 women (43%), mean age 76.2 (SD 3.9) years) entered the study; of which, 45
completed the study. METHODS: Participants performed MSL and GS once a week in
their own home during a 6-month period. PRIMARY AND SECONDARY OUTCOMES: Repeated
MSL and GS measurements were the primary outcomes. Falls, self-management and
mobility were the secondary outcomes. RESULTS: Self-assessment of MSL and GS by
older persons is feasible. Compliance of repeatedly self-measuring MSL and GS was
good; the median number of weekly measurements was 23.0 (88%) and 21.0 (81%) for
MSL and GS, respectively. Drop-outs showed less self-management abilities
compared to the participants who completed the study (p=0.049). Linear mixed
models showed a small significant improvement in MSL and GS over time (p<0.001),
without an influence on falling. CONCLUSIONS: Most community-dwelling older
persons are able and willing to repeatedly assess their MSL and GS. Self-managing
mobility and fall risk did not increase fall occurrence. The fact that older
persons can be actively involved in their own healthcare is clinically relevant.
Further studies are needed to examine the (cost-)effectiveness of self-management
in fall prevention interventions.
PMID- 27496236
TI - Comparing the accuracy of quantitative versus qualitative analyses of interim PET
to prognosticate Hodgkin lymphoma: a systematic review protocol of diagnostic
test accuracy.
AB - INTRODUCTION: Hodgkin lymphoma is an effectively treated malignancy, yet 20% of
patients relapse or are refractory to front-line treatments with potentially
fatal outcomes. Early detection of poor treatment responders is crucial for
appropriate application of tailored treatment strategies. Tumour metabolic
imaging of Hodgkin lymphoma using visual (qualitative) 18-fluorodeoxyglucose
positron emission tomography (FDG-PET) is a gold standard for staging and final
outcome assessment, but results gathered during the interim period are less
accurate. Analysis of continuous metabolic-morphological data (quantitative) FDG
PET may enhance the robustness of interim disease monitoring, and help to improve
treatment decision-making processes. The objective of this review is to compare
diagnostic test accuracy of quantitative versus qualitative interim FDG-PET in
the prognostication of patients with Hodgkin lymphoma. METHODS: The literature on
this topic will be reviewed in a 3-step strategy that follows methods described
by the Joanna Briggs Institute (JBI). First, MEDLINE and EMBASE databases will be
searched. Second, listed databases for published literature (MEDLINE,
Tripdatabase, Pedro, EMBASE, the Cochrane Central Register of Controlled Trials
and WoS) and unpublished literature (Open Grey, Current Controlled Trials,
MedNar, ClinicalTrials.gov, Cos Conference Papers Index and International
Clinical Trials Registry Platform of the WHO) will be queried. Third, 2
independent reviewers will analyse titles, abstracts and full texts, and perform
hand search of relevant studies, and then perform critical appraisal and data
extraction from selected studies using the DATARI tool (JBI). If possible, a
statistical meta-analysis will be performed on pooled sensitivity and specificity
data gathered from the selected studies. Statistical heterogeneity will be
assessed. Funnel plots, Begg's rank correlations and Egger's regression tests
will be used to detect and/or correct publication bias. ETHICS AND DISSEMINATION:
The results will be disseminated by publishing in a peer-reviewed journal.
Ethical assessment will not be needed; only existing sources of literature will
be searched. TRIAL REGISTRATION NUMBER: CRD42016027953.
PMID- 27496237
TI - Estimating the economic burden of cardiovascular events in patients receiving
lipid-modifying therapy in the UK.
AB - OBJECTIVES: To characterise the costs to the UK National Health Service of
cardiovascular (CV) events among individuals receiving lipid-modifying therapy.
DESIGN: Retrospective cohort study using Clinical Practice Research Datalink
records from 2006 to 2012 to identify individuals with their first and second CV
related hospitalisations (first event and second event cohorts). Within-person
differences were used to estimate CV-related outcomes. SETTING: Patients in the
UK who had their first CV event between January 2006 and March 2012.
PARTICIPANTS: Patients >=18 years who had a CV event and received at least 2
lipid-modifying therapy prescriptions within 180 days beforehand. PRIMARY AND
SECONDARY OUTCOME MEASURES: Direct medical costs (2014 L) were estimated in 3
periods: baseline (pre-event), acute (6 months afterwards) and long-term
(subsequent 30 months). Primary outcomes included incremental costs, resource
usage and total costs per period. RESULTS: There were 24 093 patients in the
first event cohort of whom 5274 were included in the second event cohort. The
mean incremental acute CV event costs for the first event and second event
cohorts were: coronary artery bypass graft/percutaneous transluminal coronary
angioplasty (CABG/PTCA) L5635 and L5823, myocardial infarction L4275 and L4301,
ischaemic stroke L3512 and L4572, heart failure L2444 and L3461, unstable angina
L2179 and L2489 and transient ischaemic attack L1537 and L1814. The mean
incremental long-term costs were: heart failure L848 and L2829, myocardial
infarction L922 and L1385, ischaemic stroke L973 and L682, transient ischaemic
attack L705 and L1692, unstable angina L328 and L677, and CABG/PTCA L-368 and
L599. Hospitalisation accounted for 95% of acute and 61% of long-term incremental
costs. Higher comorbidity was associated with higher long-term costs.
CONCLUSIONS: Revascularisation and myocardial infarction were associated with the
highest incremental costs following a CV event. On the basis of real-world data,
the economic burden of CV events in the UK is substantial, particularly among
those with greater comorbidity burden.
PMID- 27496238
TI - Understanding and reducing the prescription of hypnotics and sedatives at the
interface of hospital care and general practice: a protocol for a mixed-methods
study.
AB - INTRODUCTION: Hypnotics and sedatives, especially benzodiazepines and Z-drugs,
are frequently prescribed for longer periods than recommended-in spite of
potential risks for patients. Any intervention to improve this situation has to
take into account the interplay between different actors, interests and needs.
The ultimate goal of this study is to develop-together with the professionals
involved-ideas for reducing the use of hypnotics and sedatives and then to
implement and evaluate adequate interventions in the hospital and at the primary
and secondary care interface. METHODS AND ANALYSIS: The study will take place in
a regional hospital in northern Germany and in some general practices in this
region. We will collect data from doctors, nurses, patients and a major social
health insurer to define the problem from multiple perspectives. These data will
be explored and discussed with relevant stakeholders to develop interventions.
The interventions will be implemented and, in a final step, evaluated. Both
quantitative and qualitative data, including surveys, interviews, chart reviews
and secondary analysis of social health insurance data, will be collected to
obtain a full understanding of the frequency and the reasons for using hypnotics
and sedatives. ETHICS AND DISSEMINATION: Approval has been granted from the
ethics review committee of the University Medical Center Gottingen, Germany.
Results will be disseminated to researchers, clinicians and policy makers in peer
reviewed journal articles and conference publications. One or more dissemination
events will be held locally during continuous professional development events for
local professionals, including (but not confined to) the study participants.
PMID- 27496239
TI - Nutritional route in oesophageal resection trial II (NUTRIENT II): study protocol
for a multicentre open-label randomised controlled trial.
AB - INTRODUCTION: Early start of an oral diet is safe and beneficial in most types of
gastrointestinal surgery and is a crucial part of fast track or enhanced recovery
protocols. However, the feasibility and safety of oral intake directly following
oesophagectomy remain unclear. The aim of this study is to investigate the
effects of early versus delayed start of oral intake on postoperative recovery
following oesophagectomy. METHODS AND ANALYSIS: This is an open-label multicentre
randomised controlled trial. Patients undergoing elective minimally invasive or
hybrid oesophagectomy for cancer are eligible. Further inclusion criteria are
intrathoracic anastomosis, written informed consent and age 18 years or older.
Inability for oral intake, inability to place a feeding jejunostomy, inability to
provide written consent, swallowing disorder, achalasia, Karnofsky Performance
Status <80 and malnutrition are exclusion criteria. Patients will be randomised
using online randomisation software. The intervention group (direct oral feeding)
will receive a liquid oral diet for 2 weeks with gradually expanding daily
maximums. The control group (delayed oral feeding) will receive enteral feeding
via a jejunostomy during 5 days and then start the same liquid oral diet. The
primary outcome measure is functional recovery. Secondary outcome measures are 30
day surgical complications; nutritional status; need for artificial nutrition;
need for additional interventions; health-related quality of life. We aim to
recruit 148 patients. Statistical analysis will be performed according to an
intention to treat principle. Results are presented as risk ratios with
corresponding 95% CIs. A two-tailed p<0.05 is considered statistically
significant. ETHICS AND DISSEMINATION: Our study protocol has received ethical
approval from the Medical research Ethics Committees United (MEC-U). This study
is conducted according to the principles of Good Clinical Practice. Verbal and
written informed consent is required before randomisation. All data will be
collected using an online database with adequate security measures. TRIAL
REGISTRATION NUMBERS: NCT02378948 and Dutch trial registry: NTR4972; Pre-results.
PMID- 27496240
TI - Study on the development of an infectious disease-specific health literacy scale
in the Chinese population.
AB - OBJECTIVES: To develop a scale to assess infectious disease-specific health
literacy (IDSHL) in China and test its initial psychometric properties. METHODS:
Item pooling, reduction and assessment of psychometric properties were conducted.
The scale was divided into 2 subscales; subscale 1 assessed an individual's
skills to prevent/treat infectious diseases and subscale 2 assessed cognitive
ability. In 2014, 9000 people aged 15-69 years were randomly sampled from 3
provinces and asked to complete the IDSHL questionnaire. Cronbach's alpha was
calculated to assess reliability. Exploratory factor analysis, t-test,
correlations, receiver operating characteristic (ROC) curve and logistic
regression were used to examine validity. RESULTS: Each of the 22 items in
subscale 1 had a content validity index >0.8. In total, 8858 people completed the
scale. The principal components factor analysis suggested a 5-factor solution.
All factor loadings were >0.40 (p<0.05). The IDSHL score was 22.07+/-7.91 (mean+/
SD; total score=38.62). Significant differences were observed across age (r=
0.276), sex (males: 21.65+/-8.03; females: 22.47+/-7.78), education (14.16+/-8.19
to 26.55+/-6.26), 2-week morbidity (present: 20.62+/-8.17, absent: 22.35+/-7.83;
p<0.001) and health literacy of the highest and lowest 27% score groups (all
p<0.05). The ROC curve indicated that 76.2% of respondents were adequate in
IDSHL. Binary logistic regression analysis revealed 12 predictors of IDSHL
adequacy (p<0.05). Among the 22 remaining items, Corrected Item-Total Correlation
ranged from 0.316 to 0.504 and Cronbach's alpha values ranged from 0.754 to 0.810
if the items were deleted. The overall alpha value was 0.839 and the difficulty
coefficient ranged from 1.19 to 4.08. For subscale 2, there were statistically
significant differences between the mean scores of those with a correct/incorrect
answer (all p<0.001). CONCLUSIONS: The newly developed 28-item scale provides an
efficient, psychometrically sound and user-friendly measure of IDSHL in the
Chinese population.
PMID- 27496241
TI - Nurses' sleep quality, work environment and quality of care in the Spanish
National Health System: observational study among different shifts.
AB - OBJECTIVE: The main objective of this study was to determine the relationship
between the characteristics of nurses' work environments in hospitals in the
Spanish National Health System (SNHS) with nurse reported quality of care, and
how care was provided by using different shifts schemes. The study also examined
the relationship between job satisfaction, burnout, sleep quality and daytime
drowsiness of nurses and shift work. METHODS: This was a multicentre,
observational, descriptive, cross-sectional study, centred on a self-administered
questionnaire. The study was conducted in seven SNHS hospitals of different
sizes. We recruited 635 registered nurses who worked on day, night and rotational
shifts on surgical, medical and critical care units. Their average age was 41.1
years, their average work experience was 16.4 years and 90% worked full time. A
descriptive and bivariate analysis was carried out to study the relationship
between work environment, quality and safety care, and sleep quality of nurses
working different shift patterns. RESULTS: 65.4% (410) of nurses worked on a
rotating shift. The Practice Environment Scale of the Nursing Work Index
classification ranked 20% (95) as favourable, showing differences in nurse
manager ability, leadership and support between shifts (p=0.003). 46.6% (286)
were sure that patients could manage their self-care after discharge, but there
were differences between shifts (p=0.035). 33.1% (201) agreed with information
being lost in the shift change, showing differences between shifts (p=0.002). The
Pittsburgh Sleep Quality Index reflected an average of 6.8 (SD 3.39), with
differences between shifts (p=0.017). CONCLUSIONS: Nursing requires shift work,
and the results showed that the rotating shift was the most common. Rotating
shift nurses reported worse perception in organisational and work environmental
factors. Rotating and night shift nurses were less confident about patients'
competence of self-care after discharge. The most common nursing care omissions
reported were related to nursing care plans. For the Global Sleep Quality score,
difference were found between day and night shift workers.
PMID- 27496242
TI - Effect of warning symbols in combination with education on the frequency of
erroneously crushing medication in nursing homes: an uncontrolled before and
after study.
AB - OBJECTIVES: Residents of nursing homes often have difficulty swallowing
(dysphagia), which complicates the administration of solid oral dosage
formulations. Erroneously crushing medication is common, but few interventions
have been tested to improve medication safety. Therefore, we evaluated the effect
of warning symbols in combination with education on the frequency of erroneously
crushing medication in nursing homes. SETTING: This was a prospective
uncontrolled intervention study with a preintervention and postintervention
measurement. The study was conducted on 18 wards (total of 200 beds) in 3 nursing
homes in the North of the Netherlands. PARTICIPANTS: We observed 36
nurses/nursing assistants (92% female; 92% nursing assistants) administering
medication to 197 patients (62.9% female; mean age 81.6). INTERVENTION: The
intervention consisted of a set of warning symbols printed on each patient's unit
dose packaging indicating whether or not a medication could be crushed as well as
education of ward staff (lectures, newsletter and poster). PRIMARY OUTCOME
MEASURE: The relative risk (RR) of a crushing error occurring in the
postintervention period compared to the preintervention period. A crushing error
was defined as the crushing of a medication considered unsuitable to be crushed
based on standard reference sources. Data were collected using direct (disguised)
observation of nurses during drug administration. RESULTS: The crushing error
rate decreased from 3.1% (21 wrongly crushed medicines out of 681
administrations) to 0.5% (3/636), RR=0.15 (95% CI 0.05 to 0.51). Likewise, there
was a significant reduction using data from patients with swallowing difficulties
only, 87.5% (21 errors/24 medications) to 30.0% (3/10) (RR 0.34, 95% CI 0.13 to
0.89). Medications which were erroneously crushed included enteric-coated
formulations (eg, omeprazole), medication with regulated release systems (eg,
Persantin; dipyridamol) and toxic substances (eg, finasteride). CONCLUSIONS:
Warning symbols combined with education reduced erroneous crushing of medication,
a well-known and common problem in nursing homes.
PMID- 27496244
TI - Eccentric small-zone ray tracing wavefront aberrometry for refraction in
keratoconus.
AB - PURPOSE: To compare objective refraction using small-zone eccentric laser ray
tracing (LRT) wavefront aberrometry to standard autorefraction in keratoconus
(KC), and whether the visual acuities achieved with these refractions differ from
corresponding values in healthy eyes. METHODS: Twenty-nine eyes of 29 patients
with KC and 29 eyes of 29 healthy controls were included in this prospective
unmasked case-control study. The uncorrected (UCVA) and spectacle-corrected
(SCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuities based
on refractions derived from LRT in central and four eccentric zones were compared
to those achieved with standard autorefraction. The spherical equivalent (M) and
two astigmatic power vectors (C0 and C45) were calculated for all refractions.
Pentacam HR(r) was used to generate keratometry readings of the corresponding
zones. RESULTS: In KC, the refraction from the upper nasal zone rendered a higher
SCVA than the standard autorefraction more often than in the controls (p <
0.001). There were no significant variation in M between the different LRT
measurement points in the control group, but central data provided the best SCVA.
The UCVA:s and SCVA:s were worse in KC, and the KC eyes showed inferior myopia
and superior hyperopia. Multiple refractions rendered similar SCVA:s in KC.
Pentacam HR(r) showed higher keratometry readings infero-temporally, but also
lower readings supero-nasally, compared to controls. CONCLUSION: In KC, eccentric
LRT measurements gave better SCVA than standard autorefraction more often than in
healthy eyes. Eccentric LRT may become a valuable tool in the demanding task of
subjective refraction in KC.
PMID- 27496243
TI - Development and initial cohort validation of the Arthritis Research UK
Musculoskeletal Health Questionnaire (MSK-HQ) for use across musculoskeletal care
pathways.
AB - OBJECTIVES: Current musculoskeletal outcome tools are fragmented across different
healthcare settings and conditions. Our objectives were to develop and validate a
single musculoskeletal outcome measure for use throughout the pathway and
patients with different musculoskeletal conditions: the Arthritis Research UK
Musculoskeletal Health Questionnaire (MSK-HQ). SETTING: A consensus workshop with
stakeholders from across the musculoskeletal community, workshops and individual
interviews with a broad mix of musculoskeletal patients identified and
prioritised outcomes for MSK-HQ inclusion. Initial psychometric validation was
conducted in four cohorts from community physiotherapy, and secondary care
orthopaedic hip, knee and shoulder clinics. PARTICIPANTS: Stakeholders (n=29)
included primary care, physiotherapy, orthopaedic and rheumatology patients
(n=8); general practitioners, physiotherapists, orthopaedists, rheumatologists
and pain specialists (n=7), patient and professional national body
representatives (n=10), and researchers (n=4). The four validation cohorts
included 570 participants (n=210 physiotherapy, n=150 hip, n=150 knee, n=60
shoulder patients). OUTCOME MEASURES: Outcomes included the MSK-HQ's
acceptability, feasibility, comprehension, readability and responder burden. The
validation cohort outcomes were the MSK-HQ's completion rate, test-retest
reliability and convergent validity with reference standards (EQ-5D-5L, Oxford
Hip, Knee, Shoulder Scores, and the Keele MSK-PROM). RESULTS: Musculoskeletal
domains prioritised were pain severity, physical function, work interference,
social interference, sleep, fatigue, emotional health, physical activity,
independence, understanding, confidence to self-manage and overall impact.
Patients reported MSK-HQ items to be 'highly relevant' and 'easy to understand'.
Completion rates were high (94.2%), with scores normally distributed, and no
floor/ceiling effects. Test-retest reliability was excellent, and convergent
validity was strong (correlations 0.81-0.88). CONCLUSIONS: A new musculoskeletal
outcome measure has been developed through a coproduction process with patients
to capture prioritised outcomes for use throughout the pathway and with different
musculoskeletal conditions. Four validation cohorts found that the MSK-HQ had
high completion rates, excellent test-retest reliability and strong convergent
validity with reference standards. Further validation studies are ongoing,
including a cohort with rheumatoid/inflammatory arthritis.
PMID- 27496245
TI - Combined unicompartmental knee arthroplasty and anterior cruciate ligament
reconstruction in knees with osteoarthritis and deficient anterior cruciate
ligament.
AB - BACKGROUND: Relative young and more active patients with osteoarthritis (OA) of
the isolated medial femorotibial compartment in conjunction with anterior
cruciate ligament (ACL) deficiency are difficult to treat. The aim of this study
was to explore the early clinical outcomes of combined Oxford unicompartmental
knee arthroplasty (UKA) and ACL reconstruction for the patients presenting ACL
deficiency and isolated OA of the medial compartment. METHODS: Twenty-eight
patients were included into the study. All patients were treated by combined
Oxford UKA and ACL reconstruction. Plain radiographs in the antero-posterior and
lateral view and long-leg standing radiographs were routinely performed prior to
and after surgery. Stress radiographs in valgus were additionally available in
order to verify the well-preserved lateral compartment. The varus deformity of
the knee prior to surgery and the valgus degree after surgery, the posterior
slope of the tibial component and the range of motion (ROM) of the knee after
surgery were measured and recorded. Clinical evaluations include Oxford Knee
Score (OKS), Knee Society Score (KSS-clinical score; KSS-function score) and
Tegner activity score. RESULTS: All the patients were followed up for 52 +/- 8
months. The leg alignment showed 3.1 +/- 0.6 degrees of varus deformity prior to
surgery and 4.0 +/- 0.7 degrees of valgus after surgery. The OKS, KSS and Tegner
activity score improved significantly after surgery (P < 0.05). The mean ROM of
the operated knee was 123.5 +/- 2.8 degrees at the last follow-up. The posterior
slope of the tibial component was 3.9 +/- 1.2 degrees . A significant correlation
was found between them according to the Pearson's correlation (r = 0.39, P =
0.03). There were 2 patients (7 %) with the complication of mobile bearing
dislocation, and a second operation of replacing a thicker mobile bearing was
performed for them. CONCLUSION: The early clinical data have shown that combined
surgery of UKA and ACL reconstruction has revealed promising results. However,
long-term follow-up studies should be done in these patients. TRIAL REGISTRATION:
Current trial ISRCTN24663935 (Retrospectively registered on 21 July 2016).
PMID- 27496246
TI - Restorative proctocolectomy with two different pouch designs: few complications
with good function.
AB - AIM: The object of this study was to compare function and quality of life after
restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA)
surgery having two different pouch designs. METHOD: Patients having RPC in an
academic unit from 2000 who had had the loop-ileostomy closed by June 2013 were
identified from the hospital medical records. They were sent a questionnaire
regarding quality of life and interviewed using a pouch function score (PFS)
described by Oresland (score 0-16, higher scores denote worse function). RESULTS:
One hundred and three patients underwent surgery, of whom 56 had a J-pouch design
and 47 a K-pouch design, this being a double-folded Kock pouch without the nipple
valve. No patients have had the pouch removed or defunctioned due to failure at a
mean of 8 years. The reoperation rate was 11.6%. The mean PFS was 5.43 and 5.27
for J- and K-pouches, respectively (P = 0.766). More patients with a J-pouch
reported a social handicap due to poor bowel function (P = 0.041). Patients with
a PFS >= 8 had a poorer quality of life. A score of >= 8 was reported by 16% of K
pouch and 25% of J-pouch patients (P = 0.29). CONCLUSION: RPC is a safe procedure
with a low complication rate and good functional outcome. Small improvements in
function have an impact on a patient's quality of life. Although the J-pouch is
the most commonly used, the K-pouch has some advantages. Other pouch designs
deserve further evaluation.
PMID- 27496247
TI - Flavonoids stimulate cholecystokinin peptide secretion from the enteroendocrine
STC-1 cells.
AB - Animal experiments showed that flavonoids might have the potential for an anti
obesity effect by reducing weight and food intake. However, the exact mechanisms
that could be involved in these proposed effects are still under investigation.
The complex process of food intake is partially regulated by gastrointestinal
hormones. Cholecystokinin (CCK) is the best known gastrointestinal hormone to
induce satiety signal that plays a key role in food intake regulation. It is
released from the endocrine cells (I cell) in response to the ingestion of
nutrients into the small intestine. In this study, we investigated the possible
effects of flavonoids (quercetin, kaempferol, apigenin, rutin and baicalein) on
stimulation of CCK release in vitro using enteroendocrine STC-1 cells. In
comparison with the control, quercetin, kaempferol and apigenin resulted in a
significant increase in CCK secretion with quercetin showing the highest
activity. On the other hand, no significant effect was seen by rutin and
baicalein. To our knowledge, this is the first report to study the stimulation of
CCK peptide hormone secretion from STC-1 cells by quercetin and kaempferol,
rutin, apigenin and baicalein. Based on the cell-based results in this work, it
can be suggested that the reported activity of flavonoids against food intake and
weight could be mediated by stimulation of CCK signal which in turn is
responsible for food intake reduction, but future animal and human studies are
needed to confirm this conclusion at organism level.
PMID- 27496248
TI - An Evaluation of FrancoForme: A CASE-MANAGED HOME-BASED PRIMARY AND SECONDARY
CARDIOVASCULAR DISEASE PREVENTION PROGRAM FOR FRENCH-SPEAKING CANADIANS.
AB - PURPOSE: Cardiovascular disease (CVD) is the leading cause of mortality globally.
Telephone-delivered interventions targeting cardiovascular risk factors are
gaining popularity. This study is an evaluation of FrancoForme, a cardiovascular
risk factor reduction program for the primary and secondary prevention of CVD
among French-speaking patients of Eastern Ontario. METHODS: This study reports on
changes in cardiovascular risk factors, weekly exercise levels, and psychosocial
characteristics including anxiety, depression, and quality of life upon program
completion (3 months) and at 1 year after the start of the program. Repeated
measures analysis of variance was used to compare changes in outcomes between
primary prevention risk groups (low, moderate, and high risk for CVD) and the
secondary prevention group (ie, cardiac rehabilitation) at baseline, 3 months and
12 months. RESULTS: A total of 762 patients enrolled in FrancoForme between 2008
and 2015. At 3 months, all program completers (n = 507) experienced significant
reductions for all cardiovascular risk factors except diastolic blood pressure.
Minutes of self-reported exercise increased significantly by an average 90
minutes per week and all psychosocial variables improved. Significant group
effects were observed across several risk factors. Among 12-month responders (n =
240), exercise, high-density lipoproteins, triglycerides, cholesterol, and all
psychosocial variables were improved over baseline results. CONCLUSIONS:
FrancoForme is unique in targeting both the primary and secondary prevention of
CVD and removes several of the barriers to participating in a conventional CVD
prevention program for French-speaking patients. FrancoForme is successful,
receiving high satisfaction rates and resulting in significant improvements in
cardiovascular risk factors, exercise, anxiety, and depression, as well as
quality of life.
PMID- 27496250
TI - Biopsychosocial-Spiritual Factors Impacting Referral to and Participation in
Cardiac Rehabilitation for African American Patients: A SYSTEMATIC REVIEW.
AB - PURPOSE: The purposes of this systematic review were to (1) review the literature
related to the demographic and biopsychosocial-spiritual factors impacting
cardiac rehabilitation (CR) referral and participation of African American
patients with cardiovascular disease (CVD); (2) identify barriers and
facilitators to CR referral and participation for this population; (3) identify
gaps in the literature; and (4) make recommendations for future research studies
and interventions. METHODS: The Cooper 7-step protocol for research synthesis was
followed to formulate a research question and search MEDLINE via PubMed, PsycINFO
via EBSCO, and CINAHL via EBSCO. A second reviewer repeated the searches
performed by the first author in the initial review. RESULTS: A total of 1640
articles identified using the search strategy yielded 7 articles that fit the
search criteria. Most studies measured demographic or social factors. Two studies
measured biological factors, 1 study measured psychological factors, and no study
measured spiritual factors. CONCLUSIONS: According to the studies reviewed,
African American patients with CVD were less likely to receive a CR referral,
more likely to enroll in CR with more cardiovascular risk factors, and less
likely to participate in and complete CR due to factors related to low
socioeconomic status (eg, lack of insurance, work conflicts, lower level of
education) than non-Hispanic white patients. Further research is needed on the
interaction between demographic/biopsychosocial-spiritual factors and referral to
and participation of African Americans in CR in order to ensure that
interventions fit the needs of this particular population.
PMID- 27496249
TI - Effect of Chronic Kidney Disease and Supplemental Polyunsaturated Fatty Acid Use
on Exercise Levels During Cardiac Rehabilitation in Patients With Coronary Artery
Disease.
AB - PURPOSE: The correlation between chronic kidney disease (CKD) and increased
cardiovascular disease-related mortality is well established. Cardiac
rehabilitation (CR) improves exercise capacity, quality of life, and risk factors
in patients with coronary artery disease (CAD). Data on the benefits of CR in
patients with CKD are sparse. The purpose of this study was to compare outcomes
after CR in patients with CAD but normal renal function, versus those with CAD
and CKD. METHODS: We studied 804 patients with CAD entering an exercise-based CR
program. Demographics, risk factors, exercise capacity in metabolic equivalent
levels (METs), and estimated glomerular filtration rate (GFR) were recorded
before and after the 3-month CR program. Use of polyunsaturated fatty acid (PUFA)
was determined by medical records review. Stage III-V CKD (GFR <60 mL/min/1.73 m)
was present in 170 patients at baseline. RESULTS: After CR, METs improved in all
patients, although increases in patients with a GFR 30 to 59 mL/min/1.73 m
(Delta1.6) and a GFR <30 (Delta1.2) were smaller than those in patients with a
GFR >=60 (Delta2.6, P < .05 vs GFR 30-59 and GFR <30). In patients with a GFR
>=60 mL/min/1.73 m, PUFA use was associated with a 20% greater increase in MET
levels compared with nonusers (Delta3.0 vs Delta2.5, P = .02); and in patients
with a GFR 30 to 59, PUFA use was associated with 30% increase in MET level
compared with nonusers (Delta2.0 vs Delta1.4, P = .03). These observations
persisted after multivariable adjustment for baseline MET level, demographics,
and risk factors. CONCLUSIONS: Potential mitigation by PUFA of the smaller
improvement in exercise capacity with decreasing GFR requires confirmation in
prospective randomized trials.
PMID- 27496251
TI - Relevance and attitudes toward histology and embryology course through the eyes
of freshmen and senior medical students: Experience from Serbia.
AB - Histology and embryology are prerequisite for understanding the complexity of
cell and tissue organization, function and development. The aim of this study was
to examine the attitudes of medical students toward relevance of histology and
embryology in their pre-clinical and clinical medical practice. The study sample
consisted of 900 undergraduate students of 1st and 6th study year at the School
of Medicine in Belgrade, Serbia. Data were collected using an anonymous
questionnaire. Senior students reported the relevance of histology and embryology
knowledge for learning pathology, dermatology, physiology, gynecology and
obstetrics, pathophysiology and pediatrics. Examination of students' attitudes
revealed that 1st year participants more often acknowledged histology and
embryology as being of great importance for their professional career. Analysis
according to gender indicated that female students consider embryology as of
greater importance for further medical education and future clinical practice
than male students. Overall, study results suggest that medical students have a
positive attitude toward histology and embryology undergraduate course. This
evidence could be used as an additional motive for the development of histology
and embryology courses, with special emphasis on practical application of
knowledge in clinically-oriented setting.
PMID- 27496252
TI - Changes in biting forces with implant-supported overdenture in the lower jaw: A
comparison between conventional and mini implants in a pilot study.
AB - The biting ability of patients improves noticeably after receiving implant
supported overdentures in comparison to conventional complete dentures. However,
the change of biting with such treatment concepts has been quantitatively
investigated in only a limited number of studies. The aim of the present study
has been to measure the biting forces of edentulous patients with complete
dentures and after receiving implant-supported overdentures. A total of 26
edentulous patients were included. Ten patients received two to four conventional
implants (control group, O3.3-3.7mm, L11-13mm) and 16 patients received four to
five mini implants (study group, O1.8-2.4mm, L13-15mm) inserted in the mandibular
interforaminal region. All patients received a lower overdenture with ball/rubber
ring attachments and a complete denture for the maxilla. The biting forces were
measured using Prescale pressure sheets type low before the insertion of implants
and after receiving implant-supported overdenture. The measured sheets were later
scanned and analysed using FPD-8010E software. The range of biting forces before
the insertion of implants was 80N-122N for the control group and 66-88N for the
study group. After the insertion of implants, the range of biting forces
increased to 167N-235N for the control group and to 81N-138N for the study group.
However, the increase in biting forces after the insertion of implants was not
significant for either group. No significant difference was obtained between the
two implant systems. The biting forces improved after insertion of implants
regardless of which implant system was used. However, the degree of improvement
is noticeably related to the original bone quality of the mandible at the
insertion regions of implants.
PMID- 27496254
TI - Acral syringotropic melanomas with florid eccrine duct hyperplasia, a report of
two cases.
PMID- 27496253
TI - Glycated albumin is superior to glycated hemoglobin for glycemic control
assessment at an early stage of diabetes treatment: A multicenter, prospective
study.
AB - AIMS: This study was to determine whether serum glycated albumin (GA) was a
better indicator of glycemic control than hemoglobin A1c (HbA1c) when starting a
new treatment regimen for type 2 diabetes. METHODS: Newly diagnosed type 2
diabetes patients, or patients who had poor glycemic control with oral
hypoglycemic agents, were enrolled at 10 hospitals in Beijing. Serum GA, HbA1c,
fasting blood glucose (FBG), and C-peptide were assayed on Days 0, 14, 28, and 91
after treatment. RESULTS: Four hundred ninety-nine patients were enrolled. Mean
FBG, GA and HbA1c decreased significantly in patients at Days 14, 28, and 91. In
patients with improved glycemic control, the reduction of GA and HbA1c levels was
10.5+/-13.3% vs. 5.1+/-5.4% on Day 14, 16.0+/-13.4% vs. 9.0+/-7.0% on Day 28, and
18.0+/-16.7% vs. 18.3+/-9.4% on Day 91, respectively, compared with baseline
values. Changes in GA on Day 14, 28 and 91 were all closely correlated with
changes in HbA1c on Day 91. Change in GA on Day 14 was correlated with treatment
effectiveness evaluated by HbA1c on Day 91. CONCLUSIONS: GA may be a useful
marker for assessing glycemic control at an early stage of new diabetes treatment
and assist in guiding adjustments to treatment and therapy.
PMID- 27496255
TI - Is employment-focused case management effective for patients with substance use
disorders? Results from a controlled multi-site trial in Germany covering a 2
years-period after inpatient rehabilitation.
AB - BACKGROUND: Substance use disorders are associated with unemployment. An
employment-focused case management (CMRE) has been conceptualised as a specific
intervention to help substance use disorder patients return to competitive
employment immediately after inpatient rehabilitation. This study investigated
the effect of the intervention on return to work of persons with substance use
disorders. METHOD: The study was conducted in four German inpatient
rehabilitation departments, and included unemployed patients (aged between 18 and
63 years) with a main clinical diagnosis of ICD-10 F10-19 disorders. Six weeks
before discharge, patients were randomly allocated to CMRE or standard care (SC)
using a quasi-randomised approach. The primary outcome measure was integration
into competitive employment 24 months after discharge from rehabilitation.
Secondary outcome domains were abstinence, duration of employment, proportion of
publicly funded employment, satisfaction with life, precarious housing situation
and precarious financial situation, and use of follow-up services. Outcome
measures were assessed 6 weeks and 1-2 days prior to discharge, and 12 and 24
months after discharge from rehabilitation. RESULTS: One hundred sixty patients
were allocated into the CMRE group and 160 patients into the control group. 267
resp. 179 participants could be included in the analyses performed for the 12-,
and the 24-months follow-up assessments. At the study endpoint the rate of
integration into the primary labour market was 35.6 % in the CMRE group and 41.2
% in the control group, respectively (Relative Risk 0.92, 95 % CI, 0.47; 1.79).
There was a significantly higher proportion in the CMRE group, however, which
immediately after discharge linked with services of the Federal Employment Agency
or Job Centres. There were no statistically significant differences in other
outcomes between the groups. CONCLUSIONS: Compared to SC, the additional specific
CMRE intervention did not result in superior effects on return to work rates,
abstinence, satisfaction with life, and housing and precarious financial
situation. But CMRE was more effective on linking substance use disorder patients
with services of the Federal Employment Agency or Job Centres. Reasons for the
finding that such close linking does not have an impact on return to work rates
are discussed in detail. TRIAL REGISTRATION: Identifier: DRKS00003574 ; March 12,
2012. The trial was retrospectively registered.
PMID- 27496256
TI - Drug discovery for hearing loss: Phenotypic screening of chemical compounds on
primary cultures of the spiral ganglion.
AB - In the United States there are, at present, no drugs that are specifically FDA
approved to treat hearing loss. Although several clinical trials are ongoing,
including one testing D-methionine that is supported by the US Army, none of
these trials directly address the effect of noise exposure on cochlear spiral
ganglion neurons. We recently published the first report of a systematic chemical
compound screen using primary, mammalian spiral ganglion cultures in which we
were able to detect a compound and others in its class that increased neurite
elongation, a critical step in restoring cochlear synapses after noise induced
hearing loss. Here we discuss the issues, both pro and con, that influenced the
development of our approach. These considerations may be useful for future
compound screens that target the same or other attributes of cochlear spiral
ganglion neurons.
PMID- 27496257
TI - Improving dispatcher-assisted public access defibrillation use.
PMID- 27496258
TI - Getting the right bystander to the right place at the right time.
PMID- 27496259
TI - Systematic review of paediatric track and trigger systems for hospitalised
children.
AB - CONTEXT: Early and accurate recognition of the deteriorating hospitalised child
is complex. Paediatric track and trigger systems (PTTS) support clinical decision
making by 'tracking' the child's condition through monitoring of clinical signs
and 'triggering' a request for an appropriate review when pre-determined criteria
are breeched. OBJECTIVE: To describe the number and nature of published PTTS and
appraise the evidence on their validity, calibration, and effect on important
patient outcomes (death, cardiac and/or respiratory arrest, unplanned transfer to
intensive/high dependency care, immediate/urgent request for review, rapid
response system activation). METHOD: GRADE methodology. Papers identified through
electronic database and citation searching. RESULTS: Thirty-three PTTS were
identified from 55 studies. There was considerable variety in the number and type
of parameters, although all contained one or more vital signs. The evidence to
support PTTS implementation was very low and the majority of outcomes did not
achieve statistical significance. When PTTS was implemented as part of a rapid
response system, the evidence was moderate to low but there was some evidence of
a statistically significant improvement in outcome. CONCLUSION: There is now some
limited evidence for the validity and clinical utility of PTTS scores. The high
(and increasing) number of systems is a significant confounder. Further research
is needed particularly around the thresholds for the vital signs and the
reliability, accuracy and calibration of PTTS in different settings.
PMID- 27496260
TI - Ventilation fraction during the first 30s of neonatal resuscitation.
AB - AIM: Approximately 5% of newborns receive positive pressure ventilation (PPV) for
successful transition. Guidelines urge providers to ensure effective PPV for 30
60s before considering chest compressions and intravenous therapy. Pauses in this
initial PPV may delay recovery of spontaneous respiration. The aim was to find
the ventilation fraction during the first 30s of PPV in non-breathing babies.
METHODS: Prospective observational study in two hospitals in Norway. All newborns
receiving PPV immediately after delivery were included. Cameras with motion
detectors were installed at every resuscitation bay capturing both expected and
unexpected compromised newborns. We determined the cumulative number of seconds
with PPV efforts excluding pauses in infants without spontaneous breathing and
reported ventilation fraction during the first minute. Data are presented as
median (IQR). RESULTS: 110 of 3508 (3%) newborns received PPV and were filmed in
the resuscitation bays. PPV started 42 (18-78)s after arrival at the
resuscitation bay and median duration was 100 (35-225)s. Forty-eight infants
(44%) were ventilated continuously, or with minimal pause (ventilation fraction
>90%) during the first 30s of PPV. For the remaining 62 infants ventilation
fraction was 60% (39-75). PPV was interrupted due to adjustments, checking heart
rate, stimulation, administration of CPAP and suctioning. CONCLUSION: In 56% of
the neonatal resuscitations interruptions in ventilation are frequent with 60%
ventilation fraction during the first 30s of PPV. Eliminating disruption for
improved quality of PPV delivery should be emphasized when training newborn
resuscitation providers.
PMID- 27496261
TI - Reply to Letter: Could one degree in temperature change the world? Maybe for
targeted temperature management!
PMID- 27496262
TI - Amiodarone or lidocaine for cardiac arrest: A systematic review and meta
analysis.
AB - BACKGROUND: Guidelines for treatment of out-of-hospital cardiac arrest (OOH-CA)
with shockable rhythm recommend amiodarone, while lidocaine may be used if
amiodarone is not available. Recent underpowered evidence suggests that
amiodarone, lidocaine or placebo are equivalent with respect to survival at
hospital discharge, but amiodarone and lidocaine showed higher hospital admission
rates. We undertook a systematic review and meta-analysis to assess efficacy of
amiodarone vs lidocaine vs placebo. METHODS: We included studies published in
PubMed and EMBASE databases from inception until May 15th, 2016. The primary
outcomes were survival at hospital admission and discharge in OOH-CA patients
enrolled in randomized clinical trials (RCT) according to resuscitation with
amiodarone vs lidocaine vs placebo. If feasible, secondary analysis was performed
including in the analysis also patients with in-hospital CA and data from non
RCT. RESULTS: A total of seven findings were included in the metanalysis (three
RCTs, 4 non-RCTs). Amiodarone was as beneficial as lidocaine for survival at
hospital admission (primary analysis odds ratio-OR 0.86-1.23, p=0.40) and
discharge (primary analysis OR 0.87-1.30, p=0.56; secondary analysis OR 0.86
1.27, p=0.67). As compared with placebo, survival at hospital admission was
higher both for amiodarone (primary analysis OR 1.12-1.54, p<0.0001; secondary
analysis OR 1.07-1.45, p<0.005) and lidocaine (secondary analysis only OR 1.14
1.58, p=0.0005). With regards to hospital discharge there were no differences
between placebo and amiodarone (primary outcome OR 0.98-1.44, p=0.08; secondary
outcome OR 0.92-1.33, p=0.28) or lidocaine (secondary outcome only OR 0.97-1.45,
p=0.10). CONCLUSIONS: Amiodarone and lidocaine equally improve survival at
hospital admission as compared with placebo. However, neither amiodarone nor
lidocaine improve long-term outcome.
PMID- 27496263
TI - Are the literacy difficulties that characterize developmental dyslexia associated
with a failure to integrate letters and speech sounds?
AB - The 'automatic letter-sound integration hypothesis' (Blomert, ) proposes that
dyslexia results from a failure to fully integrate letters and speech sounds into
automated audio-visual objects. We tested this hypothesis in a sample of English
speaking children with dyslexic difficulties (N = 13) and samples of
chronological-age-matched (CA; N = 17) and reading-age-matched controls (RA; N =
17) aged 7-13 years. Each child took part in two priming experiments in which
speech sounds were preceded by congruent visual letters (congruent condition) or
Greek letters (baseline). In a behavioural experiment, responses to speech sounds
in the two conditions were compared using reaction times. These data revealed
faster reaction times in the congruent condition in all three groups. In a second
electrophysiological experiment, responses to speech sounds in the two conditions
were compared using event-related potentials (ERPs). These data revealed a
significant effect of congruency on (1) the P1 ERP over left frontal electrodes
in the CA group and over fronto-central electrodes in the dyslexic group and (2)
the P2 ERP in the dyslexic and RA control groups. These findings suggest that our
sample of English-speaking children with dyslexic difficulties demonstrate a
degree of letter-sound integration that is appropriate for their reading level,
which challenges the letter-sound integration hypothesis.
PMID- 27496264
TI - Coagulation Profile Dynamics in Pediatric Patients with Cushing Syndrome: A
Prospective, Observational Comparative Study.
AB - OBJECTIVE: To evaluate the association between Cushing syndrome and
hypercoagulability in children. STUDY DESIGN: A prospective, observational study
was performed of 54 patients with Cushing syndrome, 15.1 +/- 3.9 years, treated
at the National Institutes of Health Clinical Center. Coagulation profiles were
taken before and 6-12 months after surgery and compared with18 normocortisolemic
children, 13.7 +/- 3.6 years. RESULTS: At baseline, patients with Cushing
syndrome had greater levels of the procoagulant factor VIII (FVIII) vs controls
(145 IU/dL +/- 84 vs 99 +/- 47, P = .04); 6-12 months after surgery, FVIII levels
decreased to 111 +/- 47, P = .05. Patients with Cushing syndrome had greater
levels of the antifibrinolytic alpha2-antiplasmin, 96 +/- 17% vs 82 +/- 26%, P =
.015. After surgery, antifibrinolytic alpha2-antiplasmin levels decreased to 82
+/- 24%, P < .001. Anticoagulants were greater in patients with Cushing syndrome
vs controls at baseline, including protein C (138 +/- 41% vs 84 +/- 25%, P <
.001), protein S (94 +/- 19% vs 74 +/- 19%, P = .001), and antithrombin III (96
+/- 18% vs 77 +/- 13%, P < .0001). The 24-hour urinary free cortisol levels
correlated positively with FVIII levels, r = 0.43, P = .004. CONCLUSION: Children
with Cushing syndrome had elevated procoagulants, antifibrinolytics, and
anticoagulants at baseline compared with controls; normalization of coagulation
measures was seen after surgical cure. Despite the increase in anticoagulants,
hypercortisolemia is associated with a hypercoagulable state in children, as is
the case in adults. This finding has potential implications for prevention of
venous thromboembolism in children with Cushing syndrome. TRIAL REGISTRATION:
ClinicalTrials.gov:NCT00001595.
PMID- 27496265
TI - Benign Joint Hypermobility Minimally Impacts Autonomic Abnormalities in Pediatric
Subjects with Chronic Functional Pain Disorders.
AB - OBJECTIVE: To determine if children with benign joint hypermobility (BJH)
syndrome and chronic functional pain disorders have more autonomic dysfunction.
STUDY DESIGN: Retrospective chart review study of pediatric patients seen in the
pediatric neurogastroenterology and autonomic clinic who underwent autonomic
testing and had either a Beighton score of >=6 and met Brighton criteria for BJH
(with BJH) or a score of <=2 (no BJH). RESULTS: Twenty-one female subjects (10
without BJH) met inclusion criteria; 64% of BJH had diagnosis confirmed by
genetics consultation. We evaluated for postural tachycardia syndrome, syncope,
orthostatic intolerance, and orthostatic hypotension. None of these diagnoses, as
well as baseline heart rate, peak heart rate in first 10 minutes of head up tilt
(P = .35 and P = .61, respectively), and sudomotor index (suggestive of autonomic
neuropathy) (P = .58), showed differences between the groups. Age of onset of
symptoms was also similar (P = .61) (BJH vs without BJH: median [range]:15.6
years [12.9-17.5] vs 15.4 years [11.1-18.2]). There was no difference between
groups in complaints of migraine, chronic nausea, chronic fatigue,
lightheadedness, dizziness, fainting >3 times/lifetime, delayed onset of sleep,
irritable bowel syndrome, dyspepsia, abdominal migraine, functional abdominal
pain, constipation, or fibromyalgia. CONCLUSIONS: Children with chronic
functional pain disorders and BJH have autonomic testing findings and comorbid
features compared with a similar cohort of subjects without BJH, suggesting that
BJH is not the driver of the autonomic and comorbid disorders.
PMID- 27496266
TI - Kawasaki Disease and Exposure to Fine Particulate Air Pollution.
AB - OBJECTIVE: To analyze associations of short-term exposure to fine particulate
matter (diameter <= 2.5 um [PM2.5]), a measurable component of urban pollution,
with the event date of fever onset for patients with Kawasaki disease (KD)
residing in 7 metropolitan regions. STUDY DESIGN: A case-crossover study design
was used. Time trends, seasonality, month, and weekday were controlled for by
matching. We assembled PM2.5 exposure measurements from urban monitors and
imputed PM2.5 to provide day-to-day temporal variability and resolution for time
series indexes of exposures. Selected exposure windows (to 14 days) of PM2.5 were
examined. RESULTS: A total of 3009 KD events were included for which the subject
resided within a study metropolitan area and the event date occurred during years
with available PM2.5. The estimated ORs (with 95% CIs) of an event of KD
associated with a 10 ug/m(3) PM2.5 lagged moving average concentration of lagged
exposure period (ie, concurrent, preceding day[s]) revealed no evidence of a
consistent, statistically significant, positive association between elevated
PM2.5 exposure and increased risk of KD. Extended analysis with stratification by
city, sex, age, ethnic origin, incomplete or complete clinical manifestations,
the presence of coronary aneurysm, and intravenous immunoglobulin resistance did
not provide evidence of a consistent, statistically significant, positive
association between elevated exposure to PM2.5 and increased risk of KD for any
of the strata studied. CONCLUSIONS: This multicity study failed to establish a
risk of the event of KD with short-term fine particulate exposure. Our negative
findings add to the growing field of environmental epidemiology research of KD.
PMID- 27496267
TI - Geophagy Is Associated with Growth Faltering in Children in Rural Bangladesh.
AB - OBJECTIVE: To determine the relationship between geophagy (mouthing of dirt,
sand, clay, or mud) and growth faltering in young children. STUDY DESIGN: We
examined linear growth as height and weight standardized by age and sex, and
weight standardized by height, in a cohort of children aged 6-36 months in rural
Mirzapur, Bangladesh. We determined geophagy behavior at baseline through
caregiver report. Anthropometric measurements were assessed at baseline and at a
1-year follow-up. RESULTS: We found that among children not stunted at baseline,
those with caregiver-reported geophagy at baseline grew less over 1 year compared
with their peers, with a difference in the change of standardized height for age
and sex of -0.31 (95% CI, -0.61 to -0.01). CONCLUSION: These findings show that
caregiver-reported geophagy was associated with growth faltering in a pediatric
population in rural Bangladesh. Future studies are needed to learn more about
this exposure pathway and its relevance to child growth.
PMID- 27496268
TI - The Imperative Nature of Physical Exam in Identifying Pediatric Scaphoid
Fractures.
PMID- 27496269
TI - Cutaneous Nocardiosis: A Conspicuous Eyelid Eschar.
PMID- 27496270
TI - Utility of Body Mass Index in Identifying Excess Adiposity in Youth Across the
Obesity Spectrum.
AB - OBJECTIVES: To determine the proportion of youth within a given body mass index
(BMI) obesity category with excess adiposity using dual energy x-ray
absorptiometry (DXA). Furthermore, to examine whether mean differences in
cardiometabolic risk factors based upon various excess adiposity cutpoints were
present. STUDY DESIGN: DXA data from the National Health and Nutrition
Examination Survey 1999-2006 (n = 10 465; 8-20 years of age) were used for this
analysis. Obesity categories were defined using Centers for Disease Control and
prevention definitions for age and sex. Excess adiposity was defined using cohort
specific cutpoints at 75th, 85th, and 90th percentiles of DXA body fat (%) by age
and sex using quantile regression models. Additionally, we examined differences
in cardiometabolic risk factors among youth (BMI percentile >85th) above and
below various excess adiposity cutpoints. RESULTS: Nearly all youth with class 3
obesity (100% male, 100% female; 97% male, 99% female; and 95% male, 96% female;
using the 75th, 85th, and 90th DXA percentiles, respectively) and a high
proportion of those with class 2 obesity (98% male, 99% female; 92% male, 91%
female; and 76% male, 76% female) had excess adiposity. Significant discordance
was observed between BMI categorization and DXA-derived excess adiposity among
youth with class 1 obesity or overweight. Elevated cardiometabolic risk factors
were present in youth with excess adiposity, regardless of the cutpoint used.
CONCLUSIONS: BMI correctly identifies excess adiposity in most youth with class 2
and 3 obesity but a relatively high degree of discordance was observed in youth
with obesity and overweight. Cardiometabolic risk factors are increased in the
presence of excess adiposity, regardless of the cutpoint used.
PMID- 27496271
TI - mHealth Intervention to Improve Diabetes Risk Behaviors in India: A Prospective,
Parallel Group Cohort Study.
AB - BACKGROUND: In low/middle income countries like India, diabetes is prevalent and
health care access limited. Most adults have a mobile phone, creating potential
for mHealth interventions to improve public health. To examine the feasibility
and initial evidence of effectiveness of mDiabetes, a text messaging program to
improve diabetes risk behaviors, a global nonprofit organization (Arogya World)
implemented mDiabetes among one million Indian adults. OBJECTIVE: A prospective,
parallel cohort design was applied to examine whether mDiabetes improved fruit,
vegetable, and fat intakes and exercise. METHODS: Intervention participants were
randomly selected from the one million Nokia subscribers who elected to opt in to
mDiabetes. Control group participants were randomly selected from non-Nokia
mobile phone subscribers. mDiabetes participants received 56 text messages in
their choice of 12 languages over 6 months; control participants received no
contact. Messages were designed to motivate improvement in diabetes risk
behaviors and increase awareness about the causes and complications of diabetes.
Participant health behaviors (exercise and fruit, vegetable, and fat intake) were
assessed between 2012 and 2013 via telephone surveys by blinded assessors at
baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015.
RESULTS: 982 participants in the intervention group and 943 in the control group
consented to take the phone survey at baselne. At the end of the 6-month period,
611 (62.22%) in the intervention and 632 (67.02%) in the control group completed
the follow-up telephone survey. Participants receiving texts demonstrated greater
improvement in a health behavior composite score over 6 months, compared with
those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531.
Fewer intervention participants demonstrated health behavior decline compared
with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not
exercise were observed in those receiving messages, as compared with controls.
CONCLUSIONS: A text messaging intervention was feasible and showed initial
evidence of effectiveness in improving diabetes-related health behaviors,
demonstrating the potential to facilitate population-level behavior change in a
low/middle income country. TRIAL REGISTRATION: Australian New Zealand Clinical
Trials Registry (ACTRN): 12615000423516;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=367946&isReview=
rue (Archived by WebCite at http://www.webcitation.org/6j5ptaJgF).
PMID- 27496274
TI - [Pansclerotic morphea with a rapidly fatal outcome in an 11-year-old girl].
AB - BACKGROUND: Pansclerotic morphea is a poorly described but extremely debilitating
variant of localized scleroderma. We report a case with a rapidly fatal outcome
in an 11-year-old girl. PATIENTS AND METHODS: An 11-year-old girl with a 2-year
history of morphea presented at our institution in April 2012. The sclerosis had
started on her trunk and progressed rapidly to involve her entire skin. Initial
treatment with corticosteroids was ineffective and she presented extremely
painful ulcerations of the lower limbs. The outcome was rapidly fatal, in early
2014, due to cachexia and sepsis after two amputations and several failed
treatments including methotrexate. DISCUSSION: Pansclerotic morphea is
characterized by rapidly progressing sclerosis involving the entire skin, trophic
cutaneous ulcers, painful contraction and limited joint mobility. The prognosis
is poor since the disease has an incapacitating and potentially fatal outcome. No
reliably effective treatment has yet been established. CONCLUSION: Our case
highlights the clinical characteristics of this uncommon form of localized
scleroderma, the extremely severe prognosis, and the therapeutic challenge
involved.
PMID- 27496272
TI - Low dose ouabain stimulates NaK ATPase alpha1 subunit association with
angiotensin II type 1 receptor in renal proximal tubule cells.
AB - Our laboratory has recently demonstrated that low concentrations of ouabain
increase blood pressure in rats associated with stimulation of NaK ATPase
activity and activation of the Src signaling cascade in NHE1-dependent manner.
Proteomic analysis of human kidney proximal tubule cells (HKC11) suggested that
the Angiotensin II type 1 receptor (AT1R) as an ouabain-associating protein. We
hypothesize that ouabain-induced stimulation of NaK ATPase activity is mediated
through AT1R. To test this hypothesis, we examined the effect of ouabain on renal
cell angiotensin II production, the effect of AT1R inhibition on ouabain
stimulated NKA activity, and the effect of ouabain on NKA-AT1R association.
Ouabain increased plasma angiotensin II levels in rats treated with ouabain
(1MUg/kg body wt./day) for 9days and increased angiotensin II levels in cell
culture media after 24h treatment with ouabain in human (HKC11), mouse (MRPT),
and human adrenal cells. Ouabain 10pM stimulated NKA-mediated 86Rb uptake and
phosphorylation of EGFR, Src, and ERK1/2. These effects were prevented by the
AT1R receptor blocker candesartan. FRET and TIRF microscopy using Bodipy-labeled
ouabain and mCherry-NKA or mCherry-AT1R demonstrated association of ouabain with
AT1R and NKA. Further our FRET and TIRF studies demonstrated increased
association between AT1R and NKA upon treatment with low dose ouabain. We
conclude that ouabain stimulates NKA in renal proximal tubule cells through an
angiotensin/AT1R-dependent mechanism and that this pathway contributes to cardiac
glycoside associated hypertension.
PMID- 27496275
TI - Are state laws granting pharmacists authority to vaccinate associated with HPV
vaccination rates among adolescents?
AB - OBJECTIVES: We explored whether state laws allowing pharmacists to administer
human papillomavirus (HPV) vaccinations to adolescents are associated with a
higher likelihood of HPV vaccine uptake. METHODS: We examined provider-reported
HPV vaccination among 13-17year olds in the National Immunization Survey-Teen:
2008-2014 for girls (N=48,754) and 2010-2014 for boys (N=31,802). Outcome
variables were HPV vaccine initiation (?1 dose) and completion (?3 doses). The
explanatory variable of interest was a categorical variable for the type of
pharmacist authority regarding HPV vaccination for adolescents (<18years) in the
state: not permitted (reference), by prescription, by collaborative practice
protocol, or independent authority. We ran separate difference-in-difference
regression models by sex. RESULTS: During 2008-2014, 15 states passed laws
allowing pharmacists to administer HPV vaccine to adolescents. Pharmacist
authority laws were not statistically significantly associated with increased HPV
vaccine initiation or completion. CONCLUSIONS: As currently implemented, state
laws allowing pharmacists to administer HPV vaccine to adolescents were not
associated with uptake. Possible explanations that need further research include
restrictions on pharmacists' third-party billing ability and the lack of
promotion of pharmacy vaccination services to age-eligible adolescents.
PMID- 27496276
TI - High frequency ultrasound to assess skin thickness in healthy adults.
AB - BACKGROUND: Intradermal immunization is gaining increased attention due to
multiple factors: (1) intradermal (ID) vaccination has been shown to induce
improved immunogenicity compared to intramuscular (IM) vaccination; (2) ID
vaccination has been shown to have a dose-sparing potential over IM leading to a
reduced vaccine cost and an increased availability of vaccines worldwide.
However, the currently used Mantoux technique for ID injection is difficult to
standardize and requires training. The aim of the study was (1) to assess the
epidermal and dermal thickness at the proximal ventral and dorsal forearm (PVF &
PDF) and deltoid in adults aged 18-65years (2) to determine the maximum
penetration depth and needle characteristics for the development of a platform of
medical devices suited for intradermal injection, VAX-IDTM. MATERIALS AND
METHODS: Mean thickness of the PVF, PDF and deltoid were measured using high
frequency ultrasound of healthy adults aged 18-65years. Correlation with gender,
age and BMI was assessed using Mann-Whitney U Test, Spearman correlation and
Wilcoxon Signed Ranks Test, respectively. RESULTS: Results showed an overall mean
skin thickness of 1.19mm (0.65-1.55mm) at the PVF, 1.44mm (0.78-1.84mm) at the
PDF, and 2.12mm (1,16-3.19mm) at the deltoid. Thickness of PVF & PDF and deltoid
were significantly different for men vs women (pmean<0.001, <0.001, <0.001, and
pmin<0.001, 0.012, <0.001, respectively). A significant association was found for
age at the deltoid region (p<0.001). Skin thickness for PVF, PDF & deltoid was
significantly associated to BMI (p<0.001). CONCLUSION: Significant differences in
skin thickness were seen for the PVF, PDF and deltoid region for gender, and BMI.
Age only influenced the skin thickness at deltoid region. A needle length of
1.0mm is best option for intradermal injection at the dorsal forearm
(NCT02363465).
PMID- 27496277
TI - Usability evaluation of intradermal adapters (IDA).
AB - Intradermal adapter device technology minimizes the complexity of the Mantoux
technique, thereby providing predictable, reproducible intradermal (ID)
injections and removing the concerns regarding the ease and reliability of
Mantoux technique when using conventional needle and syringe. The technology
employs a simple device with geometry designed to gently deform the skin surface
and the subcutaneous tissue, providing the ideal angle and depth of needle
insertion for consistently successful intradermal injections. The results of this
development were presented at the First, Second and Third Skin Vaccination
Summits in 2011, 2013 and 2015 respectively [1,2,3]. The current publication
addresses the performance of intradermal adapters (IDA) evaluated in three
preclinical studies. The evaluations were based on the assessment of bleb
formation in a skin model, an accepted indicator of ID injection success. All
evaluated devices share the same proprietary dermal interface technology. Devices
instituting this design are easy to use, require minimal training, and employ
conventionally molded parts and cannula. These studies evaluated IDAs of initial
design integral with luer lock needles, IDAs for use with conventional syringes,
and intradermal adapters for use with auto disable syringes (ADID adapters). The
evaluated ID adapters were intended to consistently place the lancet of the
needle at a depth of 0.75mm from the skin's surface. This placement depth
addresses the variation in the skin thickness at immunization sites for the
majority of patients independent of many other variables. Most participants
preferred the intradermal adapter method over the traditional Mantoux and
identified a need for the adapter at their workplace. Evaluation of IDAs by
registered nurses indicated these devices increase success of bleb formation. The
use of IDA increased the success of forming blebs by about 30%. Nurses felt the
injections were much easier to perform, in particular by novices.
PMID- 27496278
TI - Proteome-wide antigen discovery of novel protective vaccine candidates against
Staphylococcus aureus infection.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly growing problem,
especially in hospitals where MRSA cause increased morbidity and mortality and a
significant rise in health expenditures. As many strains of MRSA are resistant to
other antimicrobials in addition to methicillin, there is an urgent need to
institute non-antimicrobial measures, such as vaccination, against the spread of
MRSA. With the aim of finding new protective antigens for vaccine development,
this study used a proteome-wide in silico antigen prediction platform to screen
the proteome of S. aureus strain MRSA252. Thirty-five different S. aureus
proteins were identified, recombinantly expressed, and tested for protection in a
lethal sepsis mouse model using S. aureus strain MRSA252 as the challenge
organism. We found that 13 of the 35 recombinant peptides yielded significant
protection and that 12 of these antigens were highly conserved across 70
completely sequenced S. aureus strains. Thus, this in silico platform was capable
of identifying novel candidates for inclusion in future vaccines against MRSA.
PMID- 27496279
TI - Viscoelasticity of Tendons Under Transverse Compression.
AB - Tendons are highly anisotropic and also viscoelastic. For understanding and
modeling their 3D deformation, information is needed on their viscoelastic
response under off-axis loading. A study was made, therefore, of creep and
recovery of bovine digital extensor tendons when subjected to transverse
compressive stress of up to ca. 100 kPa. Preconditioned tendons were compression
tested between glass plates at increasing creep loads. The creep response was
anomalous: the relative rate of creep reduced with the increasing stress. Over
each ca. 100 s creep period, the transverse creep deformation of each tendon
obeyed a power law dependence on time, with the power law exponent falling from
ca. 0.18 to an asymptote of ca. 0.058 with the increasing stress. A possible
explanation is stress-driven dehydration, as suggested previously for the similar
anomalous behavior of ligaments. Recovery after removal of each creep load was
also anomalous. Relative residual strain reduced with the increasing creep
stress, but this is explicable in terms of the reducing relative rate of creep.
When allowance was made for some adhesion occurring naturally between tendon and
the glass plates, the results for a given load were consistent with creep and
recovery being related through the Boltzmann superposition principle (BSP). The
tendon tissue acted as a pressure-sensitive adhesive (PSA) in contact with the
glass plates: explicable in terms of the low transverse shear modulus of the
tendons.
PMID- 27496280
TI - Long-term (5 years) cryopreserved spermatogonia have high capacity to generate
functional gametes via interspecies transplantation in salmonids.
AB - Although sperm cryopreservation is a powerful tool widely applicable in
biodiversity conservation and broodstock management, cryopreservation of teleost
eggs and embryos remains challenging. In the present study, we demonstrated that
spermatogonia of rainbow trout (Oncorhynchus mykiss) cryopreserved for 5 years
possessed the ability to differentiate into functional eggs or sperm in the
gonads of triploid recipient masu salmon (Oncorhynchus masou). After
cryopreservation for 5 years in liquid nitrogen, intraperitoneally transplanted
spermatogonia migrated toward, and incorporated into, the gonads of xenogeneic
recipients. The transplanted spermatogonia resumed spermatogenesis and oogenesis
in male and female recipients, respectively, and differentiated into sperm or
eggs within the gonads of male and female recipients at 2 years
posttransplantation. The differentiated sperm and eggs generated normal rainbow
trout representative of donor phenotypes. Thus, cryopreservation of spermatogonia
is a powerful and reliable method for long-term preservation of fish genetic
resources.
PMID- 27496281
TI - Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating
enzyme.
AB - Modifications of the bacterial ribosome regulate the function of the ribosome and
modulate its susceptibility to antibiotics. By modifying a highly conserved
adenosine A2503 in 23S rRNA, methylating enzyme Cfr confers resistance to a range
of ribosome-targeting antibiotics. The same adenosine is also methylated by RlmN,
an enzyme widely distributed among bacteria. While RlmN modifies C2, Cfr modifies
the C8 position of A2503. Shared nucleotide substrate and phylogenetic
relationship between RlmN and Cfr prompted us to investigate evolutionary origin
of antibiotic resistance in this enzyme family. Using directed evolution of RlmN
under antibiotic selection, we obtained RlmN variants that mediate low-level
resistance. Surprisingly, these variants confer resistance not through the Cfr
like C8 methylation, but via inhibition of the endogenous RlmN C2 methylation of
A2503. Detection of RlmN inactivating mutations in clinical resistance isolates
suggests that the mechanism used by the in vitro evolved variants is also
relevant in a clinical setting. Additionally, as indicated by a phylogenetic
analysis, it appears that Cfr did not diverge from the RlmN family but from
another distinct family of predicted radical SAM methylating enzymes whose
function remains unknown.
PMID- 27496282
TI - tRNA anticodon loop modifications ensure protein homeostasis and cell
morphogenesis in yeast.
AB - Using budding yeast, we investigated a negative interaction network among genes
for tRNA modifications previously implicated in anticodon-codon interaction: 5
methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U34: ELP3, URM1), pseudouridine
(Psi38/39: DEG1) and cyclic N6-threonyl-carbamoyl-adenosine (ct6A37: TCD1). In
line with functional cross talk between these modifications, we find that
combined removal of either ct6A37 or Psi38/39 and mcm5U34 or s2U34 results in
morphologically altered cells with synthetic growth defects. Phenotypic
suppression by tRNA overexpression suggests that these defects are caused by
malfunction of tRNALysUUU or tRNAGlnUUG, respectively. Indeed, mRNA translation
and synthesis of the Gln-rich prion Rnq1 are severely impaired in the absence of
Psi38/39 and mcm5U34 or s2U34, and this defect can be rescued by overexpression
of tRNAGlnUUG Surprisingly, we find that combined modification defects in the
anticodon loops of different tRNAs induce similar cell polarity- and nuclear
segregation defects that are accompanied by increased aggregation of cellular
proteins. Since conditional expression of an artificial aggregation-prone protein
triggered similar cytological aberrancies, protein aggregation is likely
responsible for loss of morphogenesis and cytokinesis control in mutants with
inappropriate tRNA anticodon loop modifications.
PMID- 27496284
TI - James Riddick Heron.
PMID- 27496283
TI - Efficiency of integron cassette insertion in correct orientation is ensured by
the interplay of the three unpaired features of attC recombination sites.
AB - The integron is a bacterial recombination system that allows acquisition,
stockpiling and expression of cassettes carrying protein-coding sequences, and is
responsible for the emergence and rise of multiresistance in Gram-negative
bacteria. The functionality of this system depends on the insertion of
promoterless cassettes in correct orientation, allowing their expression from the
promoter located upstream of the cassette array. Correct orientation is ensured
by strand selectivity of integron integrases for the bottom strand of cassette
recombination sites (attC), recombined in form of folded single-stranded
hairpins. Here, we investigated the basis of such strand selectivity by comparing
recombination of wild-type and mutated attC sites with different lengths,
sequences and structures. We show that all three unpaired structural features
that distinguish the bottom and top strands contribute to strand selectivity. The
localization of Extra-Helical Bases (EHBs) directly favors integrase binding to
the bottom strand. The Unpaired Central Spacer (UCS) and the Variable Terminal
Structure (VTS) influence strand selectivity indirectly, probably through the
stabilization of the bottom strand and the resulting synapse due to the
nucleotide skew between the two strands. These results underscore the importance
of the single-stranded nature of the attC site that allows such tight control
over integron cassette orientation.
PMID- 27496285
TI - Decreased extrusion of calcium phosphate cement versus high viscosity PMMA cement
into spongious bone marrow-an ex vivo and in vivo study in sheep vertebrae.
AB - BACKGROUND CONTEXT: Vertebroplasty or kyphoplasty of osteoporotic vertebral
fractures bears the risk of pulmonary cement embolism (3.5%-23%) caused by
leakage of commonly applied acrylic polymethylmethacrylate (PMMA) cement to
spongious bone marrow or outside of the vertebrae. Ultraviscous cement and
specific augmentation systems have been developed to reduce such adverse effects.
Rapidly setting, resorbable, physiological calcium phosphate cement (CPC) may
also represent a suitable alternative. PURPOSE: This study aimed to compare the
intravertebral extrusion of CPC and PMMA cement in an ex vivo and in vivo study
in sheep. STUDY DESIGN/SETTING: A prospective experimental animal study was
carried out. METHODS: Defects (diameter 5 mm; 15 mm depth) were created by a
ventrolateral percutaneous approach in lumbar vertebrae of female Merino sheep (2
4 years) either ex vivo (n=17) or in vivo (n=6), and injected with: (1) CPC (L3);
(2) CPC reinforced with 10% poly(l-lactide-co-glycolide) (PLGA) fibers (L4); or
(3) PMMA cement (L5; Kyphon HV-R). Controls were untouched (L1) or empty defects
(L2). The effects of the cement injections were assessed in vivo by blood gas
analysis and ex vivo by computed tomography (CT), micro-CT (voxel size: 67 um),
histology, and biomechanical testing. RESULTS: Following ex vivo injection, micro
CT documented significantly increased extrusion of PMMA cement in comparison to
CPC (+/- fibers) starting at a distance of 1 mm from the edge of the defect
(confirmed by histology); this was also demonstrated by micro-CT following in
vivo cement injection. In addition, blood gas analysis showed consistently
significantly lower values for the fraction of oxygenized hemoglobin/total
hemoglobin (FO2Hb) in the arterial blood until 25 minutes following injection of
the PMMA cement (p <= .05 vs. CPC; 7, 15 minutes). Biomechanical testing
following ex vivo injection showed significantly lower compressive strength and
Young modulus than untouched controls for the empty defect (40% and 34%
reduction, respectively) and all three cement-injected defects (21%-27% and 29%
32% reduction, respectively), without significant differences among the cements.
CONCLUSIONS: Because of comparable compressive strength, but significantly lower
cement extrusion into spongious bone marrow than PMMA cement, physiological CPC
(+/- PLGA fibers) may represent an attractive alternative to PMMA for
vertebroplasty or kyphoplasty of osteoporotic vertebral fractures to reduce the
frequency or severity of adverse effects.
PMID- 27496287
TI - Storytelling and Consumerism.
PMID- 27496286
TI - Quality of life outcomes following cervical decompression for coexisting
Parkinson's disease and cervical spondylotic myelopathy.
AB - BACKGROUND CONTEXT: Coexisting Parkinson's disease (PD) and cervical spondylotic
myelopathy (CSM) presents a diagnostic and therapeutic challenge due to
symptomatic similarities between the diseases. Whereas CSM patients are routinely
treated with surgery, PD patients face poorer outcomes following spine surgery.
No studies have investigated the quality of life (QOL) outcomes following
decompression in coexisting PD and CSM. PURPOSE: The purpose of the present study
was to characterize QOL outcomes for patients with coexisting PD and CSM
following cervical decompression. STUDY DESIGN/SETTING: This is a matched cohort
study at a single tertiary-care center. PATIENT SAMPLE: Patients with coexisting
PD and CSM undergoing cervical decompression between June 2009 and December 2014
were included. These patients were matched to controls with CSM alone by age,
gender, American Society of Anesthesiologists classification, Modified Japanese
Orthopaedic Association scores, and operative parameters. OUTCOME MEASURES: The
primary outcome measure was QOL outcomes assessed by change in the EuroQol 5
Dimensions (EQ-5D), Pain Disability Questionnaire (PDQ), and Patient Health
Questionnaire-9 (PHQ-9) at last follow-up (LFU). Change in QOL exceeding the
minimal clinically important difference (MCID) was secondary. METHODS: QOL data
were collected using the institutional prospectively collected database of
patient-reported health status measures. Simple and multivariable regressions
were used to assess the impact of PD upon change in QOL. RESULTS: Eleven PD
patients were matched to 44 controls. Control patients experienced QOL
improvement across all three measures, whereas PD patients only improved with
respect to PDQ(89.9-80.7, p=.03). Despite no significant differences in
preoperative QOL, PD patients experienced poorer QOL at LFU in EQ-5D (0.526 vs.
0.707, p=.01) and PDQ (80.7 vs. 51.4, p=.03), and less frequently achieved an EQ
5D MCID (18% vs. 57%, p=.04). However, no differences in the achievement of an
MCID in PDQ or PHQ-9 were observed between cohorts. Multivariable regression
identified PD as a significant independent predictor of poorer improvement in EQ
5D (beta=-0.09, p<.01) and failure to achieve an EQ-5D MCID (odds ratio: 0.08,
p<.01). CONCLUSIONS: This is the first study to characterize QOL outcomes
following cervical decompression for patients with coexisting PD and CSM.
Although myelopathy may have been less severe among PD patients, a significant
reduction in pain-related disability was observed following decompression.
However, PD predicted diminished improvement in overall QOL measured by the EQ
5D.
PMID- 27496288
TI - ACR Appropriateness Criteria Low Back Pain.
AB - Most patients presenting with uncomplicated acute low back pain (LBP) and/or
radiculopathy do not require imaging. Imaging is considered in those patients who
have had up to 6 weeks of medical management and physical therapy that resulted
in little or no improvement in their back pain. It is also considered for those
patients presenting with red flags raising suspicion for serious underlying
conditions, such as cauda equina syndrome, malignancy, fracture, and infection.
Many imaging modalities are available to clinicians and radiologists for
evaluating LBP. Application of these modalities depends largely on the working
diagnosis, the urgency of the clinical problem, and comorbidities of the patient.
When there is concern for fracture of the lumbar spine, multidetector CT is
recommended. Those deemed to be interventional candidates, with LBP lasting for >
6 weeks having completed conservative management with persistent radiculopathic
symptoms, may seek MRI. Patients with severe or progressive neurologic deficit on
presentation and red flags should be evaluated with MRI. The ACR Appropriateness
Criteria are evidence-based guidelines for specific clinical conditions that are
reviewed annually by a multidisciplinary expert panel. The guideline development
and revision include an extensive analysis of current medical literature from
peer-reviewed journals and the application of well-established methodologies (the
RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment,
Development, and Evaluation) to rate the appropriateness of imaging and treatment
procedures for specific clinical scenarios. In those instances in which evidence
is lacking or equivocal, expert opinion may supplement the available evidence to
recommend imaging or treatment.
PMID- 27496289
TI - Esophageal hypersensitivity in noncardiac chest pain.
AB - Noncardiac chest pain (NCCP) is an often-encountered clinical problem. Although
many patients suffer from persistent or recurrent chest pain, treatment remains a
challenge owing to its various possible etiologies. Gastroesophageal reflux
disease (GERD) is the most common cause of NCCP. In GERD-related NCCP, proton
pump inhibitor treatment appears to be effective. However, the pathophysiology
remains to be fully elucidated in NCCP patients without GERD. Treatment for non
GERD-related NCCP has been aimed at esophageal motility disorders and visceral
hypersensitivity. As there is growing evidence that esophageal visceral
hypersensitivity plays a role in NCCP, pain modulators have become the mainstay
of therapy in patients with non-GERD-related NCCP. However, there is an unmet
need for the treatment of esophageal hypersensitivity in NCCP due to modest
evidence for the benefit of pain modulators, including antidepressants, in non
GERD-related NCCP. Recent studies have demonstrated that esophageal mast cell
infiltration and impaired mucosal integrity are related to visceral
hypersensitivity in patients with NCCP. Thus, esophageal mast cell stabilization
and restoration of esophageal mucosal integrity could be considered potential
therapeutic targets in selected NCCP patients with hypersensitivity. However,
further observations are necessary to shed light on esophageal hypersensitivity
in NCCP.
PMID- 27496290
TI - Three-dimensional autologous cartilage framework fabrication assisted by new
additive manufactured ear-shaped templates for microtia reconstruction.
AB - BACKGROUND: During microtia reconstruction, the intraoperative design of the
cartilage framework is important for the appearance and symmetry of the bilateral
auricles. Templates (traditionally, the X-ray film template) are usually utilized
to complete the task, which can provide cues regarding size, cranioauricular
angle and positioning to the surgeons. With a combination of three-dimensional
(3D) scanning and additive manufacturing (AM) techniques, we utilized two
different ear-shaped templates (sheet moulding and 3D templates) during the
fabrication of 3D-customized autologous cartilage frameworks for auricle
reconstruction. METHODS: Forty unilateral microtia patients were included in the
study. All the patients underwent auricle reconstruction using the tissue
expanding technique assisted by the new AM templates. Images were processed using
computer-aided design software and exported to print two different AM ear-shaped
templates: sheet moulding and 3D. Both templates were assisted by the 3D
framework fabrication. The 3D images of each patient's head were captured
preoperatively using a 3D scanner. X-ray film templates were also made for the
patients. The lengths and widths of the contralateral auricles, X-ray film and
sheet moulding templates were measured in triplicate. The error of the template
and the contralateral auricle were used to compare the accuracy between the two
templates. RESULTS: Between January and May 2014, 40 unilateral microtia patients
aged 6-29 years were included in this study. All patients underwent auricle
reconstruction using autogenous costal cartilage. The sterilized AM templates
were used to assist in the framework fabrication. The operative time was
decreased by an average of 15 min compared with the method assisted by the X-ray
film template. Postoperative appearance evaluation (based on five indexes:
symmetry, length, width, cranioauricular angle and the substructure of the
reconstructed ear) was performed by both the doctors and the patients (or their
parents). Follow-up (ranging from 9 to 18 months) showed that all of the patients
obtained satisfactory results with life-like 3D configuration and symmetric
cranioauricular angle. The follow-up showed that no surgery-related complications
occurred. Comparing the accuracy of the X-ray film and sheet moulding templates,
the average errors of length were 1.8 mm +/- 1.44 mm and 0.39 mm +/- 0.35 mm,
respectively, and the average width errors were 1.32 mm +/- 0.88 mm and 0.3 mm +/
0.47 mm, respectively. The new sheet moulding template was more accurate than
the X-ray template. CONCLUSIONS: The new sheet-moulding template is much more
accurate than the traditional X-ray film template. Framework fabrication assisted
by accurate 3D and informative AM templates contributed to individualized
cartilage framework fabrication and satisfactory results.
PMID- 27496291
TI - A systematic review of the use of lasers for the treatment of hidradenitis
suppurativa.
AB - AIM: To conduct a systematic review of the effectiveness of various types of
lasers (and light based therapies) for the treatment of hidradenitis suppurativa
(HS) and to establish recommendations based on our findings. DATA SOURCES:
MEDLINE, Cochrane and PubMed databases. STUDY SELECTION: English language studies
describing the use of laser for the treatment of HS. DATA EXTRACTION: Multiple
reviewers performed independent extraction and identified 22 studies that met the
inclusion and exclusion criteria. DATA SYNTHESIS: Studies were categorised
according to grading recommendations based on evidence quality guidelines for
systematic reviews. Only 2 studies met criteria to be assigned the highest grade.
CONCLUSION: Nd:YAG laser has been shown to be effective for the treatment of HS,
as is intense pulsed light therapy (IPL) using the same principles of laser hair
removal. There is weak evidence to recommend the use of carbon dioxide, diode or
alexandrite lasers. The need for larger randomized controlled trials is
highlighted.
PMID- 27496292
TI - Absence of a conventional spindle mitotic checkpoint in the binucleated single
celled parasite Giardia intestinalis.
AB - The spindle assembly checkpoint (SAC) joins the machinery of chromosome-to
spindle microtubule attachment with that of the cell cycle to prevent
missegregation of chromosomes during mitosis. Although a functioning SAC has been
verified in a limited number of organisms, it is regarded as an evolutionarily
conserved safeguard mechanism. In this report, we focus on the existence of the
SAC in a single-celled parasitic eukaryote, Giardia intestinalis. Giardia belongs
to Excavata, a large and diverse supergroup of unicellular eukaryotes in which
SAC control has been nearly unexplored. We show that Giardia cells with absent or
defective mitotic spindles due to the inhibitory effects of microtubule poisons
do not arrest in mitosis; instead, they divide without any delay, enter the
subsequent cell cycle and even reduplicate DNA before dying. We identified a
limited repertoire of kinetochore and SAC components in the Giardia genome,
indicating that this parasite is ill equipped to halt mitosis before the onset of
anaphase via SAC control of chromosome-spindle microtubule attachment. Finally,
based on overexpression, we show that Giardia Mad2, a core SAC protein in other
eukaryotes, localizes along intracytoplasmic portions of caudal flagellar
axonemes, but never within nuclei, even in mitotic cells with blocked spindles,
where the SAC should be active. These findings are consistent with the absence of
a conventional SAC, known from yeast and metazoans, in the parasitic protist
Giardia.
PMID- 27496293
TI - Bismuth Interfacial Doping of Organic Small Molecules for High Performance n-type
Thermoelectric Materials.
AB - Development of chemically doped high performance n-type organic thermoelectric
(TE) materials is of vital importance for flexible power generating applications.
For the first time, bismuth (Bi) n-type chemical doping of organic semiconductors
is described, enabling high performance TE materials. The Bi interfacial doping
of thiophene-diketopyrrolopyrrole-based quinoidal (TDPPQ) molecules endows the
film with a balanced electrical conductivity of 3.3 S cm(-1) and a Seebeck
coefficient of 585 MUV K(-1) . The newly developed TE material possesses a
maximum power factor of 113 MUW m(-1) K(-2) , which is at the forefront for
organic small molecule-based n-type TE materials. These studies reveal that fine
tuning of the heavy metal doping of organic semiconductors opens up a new
strategy for exploring high performance organic TE materials.
PMID- 27496294
TI - Electrocardiographic Screening in National Collegiate Athletic Association
Athletes.
AB - The most effective protocol for cardiovascular screening of competitive athletes
remains highly controversial. This study was a prospective, multicenter trial of
cardiovascular screening at 35 National Collegiate Athletic Association
institutions. Screening included a standardized history and physical examination
(PE) as recommended by the American Heart Association and a 12-lead
electrocardiogram (ECG) at rest. Centralized electrocardiographic interpretation
was provided using the Seattle criteria. Athletes with screening abnormalities
underwent additional evaluation directed by the host institution medical team.
Primary outcomes included the proportion of total and false-positive screens; the
sensitivity, specificity, and positive predictive value of history, PE, and ECG;
and the prevalence of serious cardiovascular disorders associated with severe
morbidity or sudden cardiac death. From August 2012 to June 2014, 5,258 athletes
from 17 intercollegiate sports were screened: 55% men (mean age 20.1 years), 73%
Caucasian, 16% African-American, and 11% other/mixed race. At least 1 positive
cardiac symptom or family history response was reported by 1,750 athletes
(33.3%). PE was abnormal in 108 athletes (2.1%), and electrocardiographic
abnormalities were present in 192 athletes (3.7%). Thirteen athletes (0.25%) were
identified with serious cardiac conditions including hypertrophic cardiomyopathy
(1), large atrial septal defect with right ventricular dilation (1), and
ventricular pre-excitation (11). The false-positive rate for history was 33.3%,
PE 2.0%, and ECG 3.4%. The sensitivity/specificity/positive predictive value for
history was 15.4%/66.9%/0.1%, PE 7.7%/98.2%/0.9%, and ECG 100%/96.6%/6.8%. In
conclusion, electrocardiographic screening in National Collegiate Athletic
Association athletes has a low false-positive rate and provides superior accuracy
compared with a standardized history and PE to detect athletes with potentially
dangerous cardiovascular conditions.
PMID- 27496295
TI - Percutaneous Nephrolithotomy Increases the Risk of New-onset Hypertension: A
Nationwide 6-Year Follow-up Study.
AB - OBJECTIVE: To determine whether percutaneous nephrolithotomy or ureteroscopic
lithotripsy leads to the development of hypertension, using the Taiwan National
Health Insurance database. METHODS: Data were sourced from the Longitudinal
Health Insurance Database (LHID2000) of Taiwan, Republic of China, compiled by
the Taiwan National Health Insurance database from 1996 to 2010. Percutaneous
nephrolithotomy and ureteroscopic lithotripsy were studied as time-dependent
covariates in a Cox proportional hazard model to estimate the hazard ratio for
the effect of new-onset hypertension. RESULTS: A total of 2552 patients were
included, with 232 PNL percutaneous nephrolithotomy, 1160 ureteroscopic
lithotripsy patients, and 1160 comparison patients. There was a significant
difference between the incidence of new-onset hypertension between the
percutaneous nephrolithotomy and comparison groups (adjusted hazard ratio 1.48,
95% confidence interval 1.13-1.95, P = .005). The percutaneous nephrolithotomy
group also had a higher incidence of new-onset hypertension than the
ureteroscopic lithotripsy group (adjusted hazard ratio 1.39, 95% confidence
interval 1.06-1.83, P = .018). The incidence rate of new hypertension during the
follow-up period was 44.5 per 1000 person-years in the percutaneous
nephrolithotomy group, 33.0 per 1000 person-years in the ureteroscopic
lithotripsy group, and 30.2 per 1000 person-years in the comparison group.
CONCLUSION: An association exists between nephrolithiasis patients who were
treated with percutaneous nephrolithotomy and subsequent hypertension diagnosis.
Although the exact mechanisms for this phenomenon are not clear, patients who
undergo percutaneous nephrolithotomy may need close monitoring of blood pressure
during postoperative follow-up.
PMID- 27496296
TI - Predictors of Recurrence and Successful Treatment Following Obstetric Fistula
Surgery.
AB - OBJECTIVE: To determine factors contributing to recurrence and successful
treatment of obstetric fistula (OF). MATERIALS AND METHODS: Data were collected
from OF patients in Saint Luc Hospital Kisantu (DR of Congo) between 2007 and
2013. Patients underwent surgical treatment and were evaluated after a follow-up
period of 3 months. Successful treatment was defined as no or dry pads whereas
recurrence was defined as the persisting need for wearing incontinence pads
immediately after the surgery or after a period of dryness. Fistula
classification was done according to Waaldijk. Univariate and multivariate
analyses were performed using logistic regression, corrected for preoperative and
intraoperative OF characteristics. RESULTS: Median age of 166 OF patients was
29.11 +/- 9. 6 years (range 5-61). The majority of OF was type I (57.2%) followed
by type III (20.5 %). There were 20.5% who showed vaginal fibrosis during
surgical treatment. The most common location of fistula was pericervical (39.8%).
The global recurrence rate at 3 months was 28.3%, with type IIBb (100%) as most
the common recurring, followed by IIAb (66.67%) and IIAa (41.18%). There were
71.7%, 15.7%, 12%, and 0.6% patients who were considered completely cured,
partially cured (downstaged), persistent, and upstaged, respectively. OF patients
with fibrosis were 68% less likely (odds ratio 0.32, 95% confidence interval 0.14
0.73; P = .0065) to be dry in comparison to those without fibrosis. Patients with
urethral fistula were 73% less likely (odds ratio 0.27, 95% confidence interval
0.11-0.63; P = .0024) to be dry compared to other locations. CONCLUSION: This
study showed that fibrosis and urethral location are independent risk factors for
fistula recurrence or persistence following surgical fistula repair.
PMID- 27496297
TI - Commentary: Does Asymptomatic Bacteriuria Reduce the Risk of Recurrence of Non
muscle-invasive Bladder Tumors?
PMID- 27496298
TI - Detailed Cost Analysis of Robotic Sacrocolpopexy Compared to Transvaginal Mesh
Repair.
AB - OBJECTIVE: To evaluate the hospital-realized cost difference between transvaginal
mesh prolapse repair and robot-assisted sacrocolpopexy. METHODS: Consecutive
transvaginal mesh prolapse surgery and robot-assisted sacrocolpopexy cases from
January 2012 to December 2013 were evaluated. Patient clinical and operative data
were recorded. The total institutional costs (direct and indirect) for each
procedure were obtained and subcategorized by area. Independent sample t tests
and chi-squared analysis were performed. RESULTS: One hundred twenty women
underwent transvaginal mesh repair whereas 106 underwent robotic sacrocolpopexy.
Body mass index was similar between groups (28.1 vs 27.5) as was midurethral
sling placement (50% vs 59%). Robotic patients were younger (61 years vs 67
years., P < .001) and more likely to undergo concomitant hysterectomy (58.5% vs
26.7%). There were similar rates for additional compartment repairs. Amortized
costs for robotic purchase and maintenance were included with all depreciated
equipment and realized by all patients undergoing surgery. Overall mean robotic
operative time was longer with and without hysterectomy (279 minutes vs 174
minutes, P < .001 and 201 minutes vs 91 minutes, P < .001). Mean total costs were
higher with robotic technique ($9675 vs $6718, P < .001), primarily driven by
anesthesia ($1141 vs $675, P < .001), and operative ($6883 vs $4487, P < .001)
costs. No differences for total costs were seen in laboratory fees, recovery
room, or inpatient nursing. CONCLUSION: Transvaginal prolapse repair is less
costly than robotic sacrocolpopexy. Length of surgery and additional robotic
supplies drive the majority of increased operative costs. Costs attributed to
robot purchase and maintenance do not uniquely factor into the procedure costs.
PMID- 27496299
TI - Improving Outcomes of Bulbomembranous Urethroplasty for Radiation-induced
Urethral Strictures in Post-Urolume Era.
AB - OBJECTIVE: To evaluate contemporary outcomes of excision and primary anastomosis
(EPA) for the treatment of radiation-induced urethral strictures (RUS). PATIENTS
AND METHODS: A retrospective review of 72 patients undergoing EPA for RUS from
2007 to 2015 by a single surgeon was performed. We analyzed overall and long-term
success rates of EPA urethroplasty and compared patient cohorts from two groups,
2007-2012 vs 2013-2015 (post-Urolume). RESULTS: During the course of the study,
we noted a near doubling of patient volume from the earlier (6.2 patients/year)
to later (11.7 patients/year) cohorts. Among the 37 men treated from 2007 to
2012, we identified an EPA success rate of 70% compared with the improved 86%
success rate in the subsequent cohort of 35 men treated from 2013 to 2015 (P =
.07). Single dilation was successful in 50% of initial and 40% of subsequent
cohort patients in the treatment of recurrence. Initial and subsequent cohorts
varied only in regard to stricture length (mean 2.0 cm vs 3.0 cm in initial and
subsequent cohorts, P = .001) and number treated with Urolume stent (initial 5 vs
none in the later cohort, P = .03). Length of follow-up (median 50 [17-97] months
for the initial and 22 [6-34] months for the later cohort) was not associated
with recurrence. CONCLUSION: Increasing numbers of RUS patients are presenting
for urethral reconstruction in the post-Urolume era. With increasing experience,
we improved success rates of EPA urethroplasty to over 85% despite increased
stricture length.
PMID- 27496300
TI - Identifying Drivers of Episode Cost Variation With Radical Prostatectomy.
AB - OBJECTIVE: To describe total and component radical prostatectomy (RP) episode
costs across a diverse set of hospitals in Michigan, and examine drivers of
variation in such payments. METHODS: We identified Medicare and private payer
patients undergoing RP from 2012 to 2014 from the claims-based registry
maintained by the Michigan Value Collaborative, a statewide consortium that
provides hospitals with price-standardized and risk-adjusted 90-day episode costs
for common medical and surgical procedures. We divided hospitals into quartiles
based on mean total episode cost for RP. Total episode costs were further
classified into 4 payment categories: index hospitalization, professional
services, readmissions, and postacute care. Component payments were then compared
across high-cost and low-cost hospitals. RESULTS: We identified 3077 patients
undergoing RP in 42 hospitals. Mean 90-day total episode cost was $14,614,
ranging from $13,043 to $16,749 across quartiles (28.4% difference, P < .001).
Overall variation in total episode cost was divided nearly equally among
readmissions (29%), postacute care (29%), and professional payments (26%). We
noted significantly higher readmission ($1442 vs $288, P = .03) and postacute
care payments at high-cost hospitals ($1686 vs $522, P = .002). CONCLUSION:
Significant variation exists in 90-day total episode costs for RP, suggesting a
potential target for bundled payments and other care improvement efforts. Focused
efforts on reducing variation in readmissions and postacute care could improve
cost-efficiency.
PMID- 27496301
TI - The cost of local, multi-professional obstetric emergencies training.
AB - INTRODUCTION: We aim to outline the annual cost of setting up and running a
standard, local, multi-professional obstetric emergencies training course, PROMPT
(PRactical Obstetric Multi-Professional Training), at Southmead Hospital,
Bristol, UK - a unit caring for approximately 6500 births per year. MATERIAL AND
METHODS: A retrospective, micro-costing analysis was performed. Start-up costs
included purchasing training mannequins and teaching props, printing of training
materials and assembly of emergency boxes (real and training). The variable costs
included administration time, room hire, additional printing and the cost of
releasing all maternity staff in the unit, either as attendees or trainers.
Potential, extra start-up costs for maternity units without established training
were also included. RESULTS: The start-up costs were ?5574 and the variable costs
for 1 year were ?143 232. The total cost of establishing and running training at
Southmead for 1 year was ?148 806. Releasing staff as attendees or trainers
accounted for 89% of the total first year costs, and 92% of the variable costs.
The cost of running training in a maternity unit with around 6500 births per year
was approximately ?23 000 per 1000 births for the first year and around ?22 000
per 1000 births in subsequent years. CONCLUSIONS: The cost of local, multi
professional obstetric emergencies training is not cheap, with staff costs
potentially representing over 90% of the total expenditure. It is therefore vital
that organizations consider the clinical effectiveness of local training packages
before implementing them, to ensure the optimal allocation of finite healthcare
budgets.
PMID- 27496303
TI - Hodgkin lymphoma: Introduction.
PMID- 27496304
TI - Hodgkin lymphoma: Pathology and biology.
AB - The Hodgkin and Reed-Sternberg (HRS) tumor cells of classical Hodgkin lymphoma
(HL), as well as the lymphocyte predominant (LP) cells of nodular lymphocyte
predominant HL (NLPHL), are derived from mature B cells. However, HRS cells have
largely lost their B-cell phenotype and show a very unusual expression of many
markers of other hematopoietic cell lineages, which aids in the differential
diagnosis between classical HL (cHL) and NLPHL and distinguishes cHL from all
other hematopoietic malignancies. The bi- or multinucleated Reed-Sternberg cells
most likely derive from the mononuclear Hodgkin cells through a process of
incomplete cytokinesis. HRS cells show a deregulated activation of numerous
signaling pathways, which is partly mediated by cellular interactions in the
lymphoma microenvironment and partly by genetic lesions. In a fraction of cases,
Epstein-Barr virus contributes to the pathogenesis of cHL. Recurrent genetic
lesions in HRS cells identified so far often involve members of the nuclear
factor-kappaB (NF-kappaB) and JAK/STAT pathways and genes involved in major
histocompatibility complex expression. However, further lead transforming events
likely remain to be identified. We here discuss the current knowledge on HL
pathology and biology.
PMID- 27496305
TI - Clinical presentation and staging of Hodgkin lymphoma.
AB - In the present chapter the authors present a brief overview of the diagnostic
methods proposed over time for Hodgkin lymphoma (HL) spread detection, moving
from surgical procedures, through standard radiological and functional imaging
techniques to the present state of the art for HL staging. The main body of the
review will be dedicated to the recently published guidelines for lymphoma
staging (including HL) agreed by the experts during the 12th International
Congress for Malignant Lymphoma in Lugano. The recommendations of the panel on
how to integrate flurodeoxyglucose positron emission tomography (FDG-PET) scan in
the armamentarium of staging procedures will be presented and commented, with a
special emphasis on the utility of special procedures, such as bone marrow
trephine biopsy, which is deemed no longer needed in the PET era. While the HL
diagnosis is straightforward in most cases, sometimes HL is a subtle disease,
difficult to diagnose for the paucity of symptoms, the absence of physical
findings, or for concomitant immunologic disorders: a compete overview of the
common and rare patterns of HL clinical presentation will be also offered. The
future perspective of PET scan use will be based on a operator-independent,
quantitative readings of the scan thanks to a plethora of sophisticated dedicated
software, which are now available, able to quantify every voxel captured by the
tumor to display the metabolically active tumor volume. Moreover, new tracers are
now available able to track the new pathways of cellular metabolism beside
glycolysis such as amino acids or purine-analogues or specific oncoproteins; the
preliminary, promising results will be reported. Preliminary results from other
imaging techniques, such as diffusion-weighted magnetic resonance (DW-MRI) will
be also reported.
PMID- 27496302
TI - TRP channels in schistosomes.
AB - Praziquantel (PZQ) is effectively the only drug currently available for treatment
and control of schistosomiasis, a disease affecting hundreds of millions of
people worldwide. Many anthelmintics, likely including PZQ, target ion channels,
membrane protein complexes essential for normal functioning of the
neuromusculature and other tissues. Despite this fact, only a few classes of
parasitic helminth ion channels have been assessed for their pharmacological
properties or for their roles in parasite physiology. One such overlooked group
of ion channels is the transient receptor potential (TRP) channel superfamily.
TRP channels share a common core structure, but are widely diverse in their
activation mechanisms and ion selectivity. They are critical to transducing
sensory signals, responding to a wide range of external stimuli. They are also
involved in other functions, such as regulating intracellular calcium and
organellar ion homeostasis and trafficking. Here, we review current literature on
parasitic helminth TRP channels, focusing on those in schistosomes. We discuss
the likely roles of these channels in sensory and locomotor activity, including
the possible significance of a class of TRP channels (TRPV) that is absent in
schistosomes. We also focus on evidence indicating that at least one schistosome
TRP channel (SmTRPA) has atypical, TRPV1-like pharmacological sensitivities that
could potentially be exploited for future therapeutic targeting.
PMID- 27496306
TI - Prognostic factors in Hodgkin lymphoma.
AB - During the last decades, the prognosis of Hodgkin lymphoma (HL) has been improved
significantly with the introduction of effective chemotherapy and the
implementation of risk-adapted treatment approaches. Identification of reliable
risk factors is crucial to guide treatment over the course of disease. Both
clinical and biological factors have been implicated in the prognosis of HL and
are often used in prognostic scores to discriminate risk groups. To prevent under
or overtreatment, patients are usually assigned to one of the three widely
established risk groups for first-line treatment, based solely on clinical risk
factors. To further individualize therapeutic approaches, functional imaging with
positron emission tomography (PET) is becoming more widely implemented and
precisely investigated within clinical trials. Biological prognostic factors have
been widely evaluated but are still not a part of standard prognostication. This
review will discuss the currently established factors and risk models at first
diagnosis and in the setting of relapsed/refractory disease and also focus on
biological factors and PET, summarizing current standards and future
perspectives.
PMID- 27496307
TI - Treatment of early-stage Hodgkin lymphoma.
AB - Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This
is particularly true for patients with early-stage disease. Today, most patients
in this risk group are treated with a combination of chemotherapy followed by
small-field radiotherapy. More recent clinical trials such as the German Hodgkin
Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed
by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in
more than 90% of patients being cured. The current treatment for early
unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles
of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European
Organization for Research and Treatment of Cancer (EORTC) demonstrated that in
positron emission tomography (PET)-positive patients after two cycles of ABVD,
treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in
significantly improved outcomes. Other aspects including attempts to further
reduce intensity of treatment will be discussed.
PMID- 27496308
TI - Treatment of advanced-stage Hodgkin lymphoma.
AB - There is now good evidence that the escalated BEACOPP regimen (bleomycin,
etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)
is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the
widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but
the extra efficacy comes at the expense of both short- and long-term toxicity,
and there is debate as to whether overall survival is affected. Baseline
prognostic factors have proven of limited utility for determining which patients
require more intensive therapy and recent studies have sought to use interim
fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means
to guide the modulation of treatment, both upwards and downwards in intensity.
These suggest that if treatment starts with ABVD then patients remaining PET
positive after 2 months can be salvaged with escalated BEACOPP in around 65% of
cases, but those becoming PET-negative may still experience recurrences in 15%
20%, an event that is more common in those with more advanced disease at
presentation. There are early data to suggest that starting with escalated
BEACOPP may reduce the rate of recurrence after a negative interim PET to less
than 10%. This may be an attractive approach for those with very high-risk
features at presentation, but risks overtreating many patients if applied
nonselectively. New regimens incorporating antibody-drug conjugates may shift the
balance of efficacy and toxicity once again, and further studies are underway to
evaluate this.
PMID- 27496309
TI - Treatment of relapsed and refractory Hodgkin Lymphoma.
AB - Despite the high first-line cure rates in patients with Hodgkin Lymphoma (HL)
still 10%-20% of patients suffer from relapsed or refractory disease. High-dose
chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) is
standard of care for suitable patients with relapsed or refractory HL and allows
for cure in approximately 50%. Due to the poor prognosis of high-risk patients
even with HDCT and ASCT, consolidation strategies have been evaluated to improve
the cure rates. For patients with recurrence after HDCT and ASCT, treatment is
palliative in most cases. The anti-CD30 antibody-drug conjugate brentuximab
vedotin (BV) has been shown to induce high response rates in these patients;
however, durable responses were reported in a small percentage of patients only.
For carefully selected patients with multiple relapses, dose-reduced allogeneic
transplant (RICallo) is a potentially curative option. The role of RICallo will
have to be re-evaluated in the era of anti-programmed death-1 (PD1) antibodies.
PMID- 27496310
TI - Novel agents in the treatment of Hodgkin lymphoma: Biological basis and clinical
results.
AB - Hodgkin Lymphoma (HL) is a lymphoproliferative disorder of B cells that commonly
has a favorable prognosis when treated with either combination chemotherapy and
radiation therapy, or chemotherapy alone. However, the prognosis for patients who
relapse, or have evidence for refractory disease, is poor and new treatments are
needed for patients with progressive disease. HL has a unique tumor
microenvironment consisting of a predominance of inflammatory cells and a
minority of malignant Hodgkin and Reed-Sternberg (HRS) cells. This unique biology
provides an opportunity for novel therapy approaches that either specifically
target the malignant HRS cell or target the inflammatory tumor microenvironment.
New therapies including antibody drug conjugates targeting CD30, small molecule
inhibitors that inhibit critical cell signaling pathways, monoclonal antibodies
that block immune checkpoints, or agents that modulate the immune
microenvironment have all recently been tested in HL with significant clinical
activity. Multiple clinical trials are currently ongoing testing these agents in
the relapsed and refractory setting but also in earlier phases of therapy often
in combination with more standard treatment.
PMID- 27496311
TI - Nodular lymphocyte-predominant Hodgkin lymphoma.
AB - Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of
Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the
presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and
CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular
pattern. Despite frequent and often late or multiple relapses, the prognosis of
NLPHL is very favorable. There is an inherent risk of secondary aggressive non
Hodgkin lymphoma (NHL) and studies support that risk is highest in those with
splenic involvement at presentation. Given disease rarity, the optimal management
is unclear and opinions differ as to whether treatment paradigms should be
similar to or differ from those for classical Hodgkin lymphoma (CHL). This review
provides an overview of the existing literature describing pathological subtypes,
outcome and treatment approaches for NLPHL.
PMID- 27496313
TI - Hodgkin lymphoma: Late effects of treatment and guidelines for surveillance.
AB - Long-term survivors of Hodgkin lymphoma (HL) are at risk for a range of late
effects, with second malignant neoplasm and cardiovascular diseases being the
leading causes of death in these patients. The excess risks remain significantly
elevated decades after treatment, and are clearly associated with extent of
treatment exposures. Other late effects have also been identified, such as
pulmonary dysfunction, endocrinopathies, muscle atrophy, and persistent fatigue.
Systemic documentation of late effects and recognition of treatment- and patient
related risk factors are important, as they inform optimal surveillance and risk
reduction strategies, as well as guide therapeutic modifications in newly
diagnosed patients to minimize treatment-related complications. As HL therapy
evolves over time, with adoption of novel agents and contemporary treatment
techniques, late effect risks and follow-up recommendations need to be
continuously updated.
PMID- 27496312
TI - Hodgkin lymphoma in the elderly, pregnant, and HIV-infected.
AB - Hodgkin lymphoma (HL) presenting in patients with co-incidental advanced age,
pregnancy, or human immunodeficiency virus (HIV) infection is uniquely
challenging to manage. In this article we integrate recent evidence and clinical
expertise to present recommendations for diagnosis and therapeutic management.
Older patients with HL need to be carefully evaluated for comorbidies after which
judicious choice of chemotherapy should minimize functional compromise. A
pregnant patient with concurrent HL should be staged with minimal use of imaging
requiring ionizing radiation and treated in an individualized manner optimally
combining the strategies of treatment deferral when appropriate, use of single
agent vinblastine for symptomatic disease and reservation of multi-agent
chemotherapy for the small minority of patients with aggressive clinical
presentation. Treatment of HL coincident with HIV infection requires a
combination of highly active anti-retroviral agents (HAART), standard multi-agent
chemotherapy with meticulous attention to drug-drug interactions, and vigorous
supportive care to ensure the best chance of cure.
PMID- 27496314
TI - Similarity of fractionated versus single dose(s) of gemtuzumab ozogamicin as part
of the MIDAM salvage regimen in relapsed/refractory acute myeloid leukemia
patients.
PMID- 27496315
TI - Painful subcutaneous nodules in a patch of livedo reticularis.
PMID- 27496316
TI - [About the ubiquity of the alpha coefficient in the validation studies].
PMID- 27496317
TI - Clinical concentrations of morphine are cytotoxic on proliferating human
fibroblasts in vitro.
AB - BACKGROUND: Morphine and other opioids are routinely used systemically and as
wound infusions in the postoperative period. Their effect on wound and fracture
healing remains unclear. OBJECTIVE: The primary outcome was to assess the
potential cytotoxicity of clinically relevant concentrations of morphine on human
fibroblasts. DESIGN: Laboratory in-vitro study. SETTING: Institute of Physiology,
Zurich Center for Integrative Human Physiology, University of Zurich. MATERIALS:
Monolayers of human fibroblasts. INTERVENTION(S): Exposure of human fibroblast
monolayers to several concentrations of morphine, for different periods of time,
with and without an artificially induced inflammatory process. MAIN OUTCOME
MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS:
A concentration, time and exposure-dependent cytotoxic effect of morphine
mediated apoptosis was observed. Simulated inflammatory conditions seemed to
lessen toxic effects. CONCLUSION: Cytotoxic effects of morphine are exposure,
time and concentration dependent. Simulating aspects of inflammatory conditions
seems to increase resistance to morphine cytotoxicity especially in the presence
of higher concentration and longer exposure times.
PMID- 27496318
TI - Lung microbiome in human immunodeficiency virus infection.
AB - The lung microbiome plays a significant role in normal lung function and disease.
Because microbial colonization is likely influenced by immunodeficiency, one
would speculate that infection with human immunodeficiency virus (HIV) alters the
lung microbiome. Furthermore, how this alteration might impact pulmonary
complications now seen in HIV-infected patients on antiretroviral therapy (ART),
which has shifted from opportunistic infections to diseases associated with
chronic inflammation, is not known. There have been limited publications on the
lung microbiome in HIV infection, many of them emanating from the Lung HIV
Microbiome Project. Current evidence suggests that the lung microbiome in healthy
HIV-infected individuals with preserved CD4 counts is similar to uninfected
individuals. However, in individuals with more advanced disease, there is an
altered alveolar microbiome characterized by a loss of richness and evenness
(alpha diversity) within individuals. Furthermore, as a group the taxa making up
the HIV-infected and uninfected lung microbiome are different (differences in
beta diversity), and the HIV-infected population is more spread out (greater
dispersion) than the uninfected population. These differences decline with ART,
but even after effective therapy the alveolar microbiome in HIV-infected
individuals contains increased amounts of signature bacteria, some of which have
previously been associated with chronic lung inflammation. Furthermore, more
recent investigations into the lung virome in HIV infection suggest that
perturbations in lung viral communities also exist in HIV infection, and that
these too are associated with evidence of lung inflammation. Thus, it is likely
both microbiome and virome alterations in HIV infection contribute to lung
inflammation in these individuals, which has important implications on the
changing spectrum of pulmonary complications in patients living with HIV.
PMID- 27496320
TI - Priapism as a new symptom of anaphylaxis in a prepubescent child.
PMID- 27496319
TI - 1-Alpha, 25-dihydroxyvitamin D3 alters the pharmacokinetics of mycophenolic acid
in renal transplant recipients by regulating two extrahepatic UDP
glucuronosyltransferases 1A8 and 1A10.
AB - Mycophenolic acid (MPA) is an important immunosuppressant broadly used in renal
transplantation. However, the large inter-patient variability in mycophenolic
acid (MPA) pharmacokinetics (PK) limits its use. We hypothesize that extrahepatic
metabolism of MPA may have significant impact on MPA PK variability. Two
intestinal UDP-glucuronosyltransferases 1A8 and 1A10 plays critical role in MPA
metabolism. Both in silico and previous genome-wide analyses suggested that
vitamin D (VD) may regulate intestinal UGT1A expression. We validated the VD
response elements (VDREs) across the UGT1A locus with chromatin
immunoprecipitation (ChIP) and luciferase reporter assays. The impact of 1
alpha,25-dihydroxyvitamin D3 (D3) on UGT1A8 and UGT1A10 transcription and on MPA
glucuronidation was tested in human intestinal cell lines LS180, Caco-2 and HCT
116. The correlation between transcription levels of VD receptor (VDR) and the
two UGT genes were examined in human normal colorectal tissue samples (n = 73).
PK alterations of MPA following the parent drug, mycophenolate mofetil (MMF), and
D3 treatment was assessed among renal transplant recipients (n = 10). Our ChIP
assay validate three VDREs which were further demonstrated as transcriptional
enhancers with the luciferase assays. D3 treatment significantly increased
transcription of both UGT genes as well as MPA glucuronidation in cells. The VDR
mRNA level was highly correlated with that of both UGT1A8 and UGT1A10 in human
colorectal tissue. D3 treatment in patients led to about 40% reduction in both
AUC0-12 and Cmax while over 70% elevation of total clearance of MPA. Our study
suggested a significant regulatory role of VD on MPA metabolism and PK via
modulating extrahepatic UGT activity.
PMID- 27496321
TI - Interferon-Inducible Mx Promoter-Driven, Long-Term Transgene Expression System of
Interferon-beta for Cancer Gene Therapy.
AB - Gene therapy techniques aiming to induce the long-term interferon-beta (IFN-beta)
expression are desirable for inhibiting cancer growth. However, there has been no
success in this regard because IFN-beta significantly inhibits transgene
expression. This study used the IFN-inducible Mx promoter to promote IFN-beta
expression. The pMx-IFN-beta plasmid was constructed to achieve long-term IFN
beta expression. In cultured cells transfected with the Mx promoter-driven
reporter protein plasmid, IFN-beta induced concentration-dependent expression of
the reporter protein. After the hydrodynamic injection of pMx-IFN-beta into mice,
the serum concentration of IFN-beta was maintained at >=100 pg/mL for >1 month.
IFN-beta expression was significantly suppressed by the co-injection of small
interfering RNA targeting the interferon-alpha/beta receptor (IFNAR), suggesting
that IFN-beta binding to IFNAR increased IFN-beta expression. Moreover, the
hydrodynamic injection of pMx-IFN-beta significantly suppressed the growth of
colon26 tumors in mice. In contrast, a conventional promoter-driven plasmid was
less effective than pMx-IFN-beta in all the experiments. Taken together, these
results indicate that the interferon-inducible Mx promoter-driven expression
system effectively achieves long-term expression of IFN-beta and represents a
potential tool for cancer gene therapy.
PMID- 27496322
TI - Practical low-coverage genomewide sequencing of hundreds of individually barcoded
samples for population and evolutionary genomics in nonmodel species.
AB - Today most population genomic studies of nonmodel organisms either sequence a
subset of the genome deeply in each individual or sequence pools of unlabelled
individuals. With a step-by-step workflow, we illustrate how low-coverage whole
genome sequencing of hundreds of individually barcoded samples is now a practical
alternative strategy for obtaining genomewide data on a population scale. We used
a highly efficient protocol to generate high-quality libraries for ~6.5 USD from
each of 876 Atlantic silversides (a teleost fish with a genome size ~730 Mb) that
we sequenced to 1-4* genome coverage. In the absence of a reference genome, we
developed a bioinformatic pipeline for mapping the genomic reads to a de novo
assembled reference transcriptome. This provides an 'in silico' method for exome
capture that avoids the complexities and expenses of using wet chemistry for
target isolation. Using novel tools for analysis of low-coverage data, we
extracted population allele frequencies, individual genotype likelihoods and
polymorphism data for 2 504 335 SNPs across the exome for the 876 fish. To
illustrate the use of the resulting data, we present a preliminary analysis of
geographical patterns in the exome data and a comparison of complete
mitochondrial genome sequences for each individual (constructed from the low
coverage data) that show population colonization patterns along the US east
coast. With a total cost per sample of less than 50 USD (including sequencing)
and ability to prepare 96 libraries in only 5 h, our approach adds a viable new
option to the population genomics toolbox.
PMID- 27496323
TI - Mosquitoes boost body armor to resist insecticide attack.
PMID- 27496325
TI - Quantitative genetics provides predictive power for paleontological studies of
morphological evolution.
PMID- 27496324
TI - Natural search algorithms as a bridge between organisms, evolution, and ecology.
AB - The ability to navigate is a hallmark of living systems, from single cells to
higher animals. Searching for targets, such as food or mates in particular, is
one of the fundamental navigational tasks many organisms must execute to survive
and reproduce. Here, we argue that a recent surge of studies of the proximate
mechanisms that underlie search behavior offers a new opportunity to integrate
the biophysics and neuroscience of sensory systems with ecological and
evolutionary processes, closing a feedback loop that promises exciting new
avenues of scientific exploration at the frontier of systems biology.
PMID- 27496326
TI - Activated kinetics in a nonequilibrium thermal bath.
PMID- 27496327
TI - ORChestrating the human DNA replication program.
PMID- 27496328
TI - Eosinophils, galectins, and a reason to breathe.
PMID- 27496329
TI - Quantum spin dynamics with pairwise-tunable, long-range interactions.
AB - We present a platform for the simulation of quantum magnetism with full control
of interactions between pairs of spins at arbitrary distances in 1D and 2D
lattices. In our scheme, two internal atomic states represent a pseudospin for
atoms trapped within a photonic crystal waveguide (PCW). With the atomic
transition frequency aligned inside a band gap of the PCW, virtual photons
mediate coherent spin-spin interactions between lattice sites. To obtain full
control of interaction coefficients at arbitrary atom-atom separations, ground
state energy shifts are introduced as a function of distance across the PCW. In
conjunction with auxiliary pump fields, spin-exchange versus atom-atom separation
can be engineered with arbitrary magnitude and phase, and arranged to introduce
nontrivial Berry phases in the spin lattice, thus opening new avenues for
realizing topological spin models. We illustrate the broad applicability of our
scheme by explicit construction for several well-known spin models.
PMID- 27496330
TI - Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates
mammary morphogenesis.
AB - Branching morphogenesis in the mammary gland is achieved by the migration of
epithelial cells through a microenvironment consisting of stromal cells and
extracellular matrix (ECM). Here we show that galectin-1 (Gal-1), an endogenous
lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes,
induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D
organotypic cultures. Surprisingly, Gal-1's effects on mammary patterning were
independent of its glycan-binding ability and instead required localization
within the nuclei of mammary epithelia. Nuclear translocation of Gal-1, in turn,
was regulated by discrete cell-surface glycans restricted to the front of the
mammary end buds. Specifically, alpha2,6-sialylation of terminal LacNAc residues
in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear
translocation. Within mammary epithelia, Gal-1 localized within nuclear Gemini
bodies and drove epithelial invasiveness. Conversely, unsialylated LacNAc
glycans, enriched in the epithelial ducts, sequestered Gal-1 in the extracellular
environment, ultimately attenuating invasive potential. We also found that
malignant breast cells possess higher levels of nuclear Gal-1 and alpha2,6-SA and
lower levels of LacNAc than nonmalignant cells in culture and in vivo and that
nuclear localization of Gal-1 promotes a transformed phenotype. Our findings
suggest that differential glycosylation at the level of tissue microanatomy
regulates the nuclear function of Gal-1 in the context of mammary gland
morphogenesis and in cancer progression.
PMID- 27496331
TI - The Hitchhiking Parasite: Why Human Movement Matters to Malaria Transmission and
What We Can Do About It.
AB - The failure of the Global Malaria Eradication Program (GMEP) during the 1960s
highlighted the relevance of human movement to both re-introducing parasites in
elimination settings and spreading drug-resistant parasites widely. Today, given
the sophisticated surveillance of human movement patterns and key traveler
groups, it is hoped that interventions can be implemented to protect and treat
travelers, prevent onward transmission in low transmission settings, and
eliminate sources of transmission, including sources of drug-resistant parasites.
PMID- 27496332
TI - Comparative transcript profiling of alloplasmic male-sterile lines revealed
altered gene expression related to pollen development in rice (Oryza sativa L.).
AB - BACKGROUND: Cytoplasmic male sterility (CMS) is an ideal model for investigating
the mitochondrial-nuclear interaction and down-regulated genes in CMS lines which
might be the candidate genes for pollen development in rice. In this study, a set
of rice alloplasmic sporophytic CMS lines was obtained by successive backcrossing
of Meixiang B, with three different cytoplasmic types: D62A (D type), ZS97A (WA
type) and XQZ-A (DA type). RESULTS: Using microarray, the anther transcript
profiles of the three indica rice CMS lines revealed 622 differentially expressed
genes (DEGs) in each of the three CMS lines compared with the maintainer line
Meixiang B. GO and MapMan analysis indicated that these DEGs were mainly involved
in lipid metabolism and cell wall organization. Compared with the gene expression
of sporophytic and gametophytic CMS lines, 303 DEGs were identified and 56 of
them were down-regulated in all the CMS lines of rice. These down-regulated DEGs
in the CMS lines were found to be involved in tapetum or cell wall formation and
their suppressed expression might be related to male sterility. Weighted gene co
expression network analysis (WGCNA) revealed that two modules were significantly
associated with male sterility and many hub genes that were differentially
expressed in the CMS lines. CONCLUSION: A large set of putative genes involved in
anther development was identified in the present study. The results will give
some information for the nuclear gene regulation by different cytoplasmic
genotypes and provide a rich resource for further functional research on the
pollen development in rice.
PMID- 27496333
TI - Peromyscus burrowing: A model system for behavioral evolution.
AB - A major challenge to understanding the genetic basis of complex behavioral
evolution is the quantification of complex behaviors themselves. Deer mice of the
genus Peromyscus vary in their burrowing behavior, which leaves behind a physical
trace that is easily preserved and measured. Moreover, natural burrowing
behaviors are recapitulated in the lab, and there is a strong heritable
component. Here we discuss potential mechanisms driving variation in burrows with
an emphasis on two sister species: P. maniculatus, which digs a simple, short
burrow, and P. polionotus, which digs a long burrow with a complex architecture.
A forward-genetic cross between these two species identified several genomic
regions associated with burrow traits, suggesting this complex behavior has
evolved in a modular fashion. Because burrow differences are most likely due to
differences in behavioral circuits, Peromyscus burrowing offers an exciting
opportunity to link genetic variation between natural populations to evolutionary
changes in neural circuits.
PMID- 27496334
TI - Using cell deformation and motion to predict forces and collective behavior in
morphogenesis.
AB - In multi-cellular organisms, morphogenesis translates processes at the cellular
scale into tissue deformation at the scale of organs and organisms. To understand
how biochemical signaling regulates tissue form and function, we must understand
the mechanical forces that shape cells and tissues. Recent progress in developing
mechanical models for tissues has led to quantitative predictions for how cell
shape changes and polarized cell motility generate forces and collective behavior
on the tissue scale. In particular, much insight has been gained by thinking
about biological tissues as physical materials composed of cells. Here we review
these advances and discuss how they might help shape future experiments in
developmental biology.
PMID- 27496335
TI - Fast volumetric imaging of bound and pore water in cortical bone using three
dimensional ultrashort-TE (UTE) and inversion recovery UTE sequences.
AB - We report the three-dimensional ultrashort-TE (3D UTE) and adiabatic inversion
recovery UTE (IR-UTE) sequences employing a radial trajectory with conical view
ordering for bi-component T2 * analysis of bound water (T2 *(BW) ) and pore water
(T2 *(PW) ) in cortical bone. An interleaved dual-echo 3D UTE acquisition scheme
was developed for fast bi-component analysis of bound and pore water in cortical
bone. A 3D IR-UTE acquisition scheme employing multiple spokes per IR was
developed for bound water imaging. Two-dimensional UTE (2D UTE) and IR-UTE
sequences were employed for comparison. The sequences were applied to bovine bone
samples (n = 6) and volunteers (n = 6) using a 3-T scanner. Bi-component fitting
of 3D UTE images of bovine samples showed a mean T2 *(BW) of 0.26 +/- 0.04 ms and
T2 *(PW) of 4.16 +/- 0.35 ms, with fractions of 21.5 +/- 3.6% and 78.5 +/- 3.6%,
respectively. The 3D IR-UTE signal showed a single-component decay with a mean T2
*(BW) of 0.29 +/- 0.05 ms, suggesting selective imaging of bound water. Similar
results were achieved with the 2D UTE and IR-UTE sequences. Bi-component fitting
of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T2
*(BW) of 0.32 +/- 0.08 ms and T2 *(PW) of 5.78 +/- 1.24 ms, with fractions of
34.2 +/- 7.4% and 65.8 +/- 7.4%, respectively. Single-component fitting of 3D IR
UTE images showed a mean T2 *(BW) of 0.35 +/- 0.09 ms. The 3D UTE and 3D IR-UTE
techniques allow fast volumetric mapping of bound and pore water in cortical
bone. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27496336
TI - Efficacy and safety of sucroferric oxyhydroxide compared with sevelamer
hydrochloride in Japanese haemodialysis patients with hyperphosphataemia: A
randomized, open-label, multicentre, 12-week phase III study.
AB - AIM: We aimed to investigate the non-inferiority of PA21 (sucroferric
oxyhydroxide) to sevelamer hydrochloride (sevelamer) in terms of efficacy and
safety in Japanese haemodialysis patients with hyperphosphataemia. METHODS: In
this Phase III, open-label, multicentre study, 213 haemodialysis patients with
hyperphosphataemia were randomized to PA21 or sevelamer treatment for 12 weeks.
The primary outcome was adjusted serum phosphorus concentration at the end of
treatment; the non-inferiority of PA21 was confirmed if the upper limit of the
two-sided 95% confidence interval (CI) is <=0.32 mmol/L. Secondary outcomes were
corrected serum calcium and intact-parathyroid hormone concentrations. Adverse
events (AEs) and adverse drug reactions (ADRs) were evaluated. RESULTS: The
adjusted mean serum phosphorus concentration at the end of treatment confirmed
the non-inferiority of PA21 for lowering serum phosphorus compared with sevelamer
(1.62 vs 1.72 mmol/L; difference, -0.11 mmol/L; 95% CI, -0.20 to -0.02 mmol/L).
The mean daily tablet intake was 5.6 +/- 2.6 and 18.7 +/- 7.1 tablets in the PA21
and sevelamer groups, respectively. The incidences of AEs and ADRs were not
significantly different between the two groups. CONCLUSION: The non-inferiority
of PA21 to sevelamer was confirmed for the treatment of Japanese haemodialysis
patients with hyperphosphataemia. PA21 was effective, safe, and well tolerated,
while having a considerably lower pill burden than sevelamer.
PMID- 27496337
TI - High levels of stromal cell-derived factor-1alpha predict secondary cardiac
events in stable patients with a history of myocardial infarction.
AB - BACKGROUND: We recently showed that stromal cell-derived factor (SDF)-1alpha, a
pro-inflammatory mediator, is produced in infarcted myocardium and is associated
with left ventricular (LV) adverse remodeling and progressive dysfunction
following acute myocardial infarction (AMI). The current study examined whether
SDF-1alpha levels in the peripheral vein can provide prognostic information of
outcomes in stable patients with a history of MI. METHODS: Plasma levels of SDF
1alpha in the peripheral vein were measured by enzyme-linked immunosorbent assay
in 192 stable patients with a history of MI. All patients were followed
prospectively for a period of 90 months or until occurrence of one of the
following cardiac events: cardiac death, non-fatal myocardial infarction,
unstable angina requiring unplanned coronary revascularization, or worsening
heart failure requiring hospital admission. RESULTS: During the follow-up period
(77+/-26 months), 30 patients had cardiac events. Multivariate Cox analysis
revealed that high levels of SDF-1alpha (>=2162pg/mL; a cut-off value determined
by receiver-operating characteristic analysis) were a significant predictor of
cardiac events, independent of traditional risk factors (HR: 1.98; 95% CI: 1.38
2.85; p<0.001). The addition of high levels of SDF-1alpha to conventional risk
factors including brain natriuretic peptide improved net reclassification
improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.90,
p<0.0001; and IDI 0.05, p=0.002). CONCLUSIONS: High levels of SDF-1alpha
predicted secondary cardiac events in stable patients with a history of MI. SDF
1alpha levels may be a useful risk assessment tool in patients with a history of
MI.
PMID- 27496339
TI - Vitreous and subretinal fluid concentrations of orally administered dabigatran in
patients with rhegmatogenous retinal detachment.
AB - PURPOSE: One of the factors that was shown to contribute to the development of
proliferative vitreoretinopathy (PVR) is the coagulation factor thrombin.
Therefore, a specific oral thrombin inhibitor such as dabigatran might be a
possible therapeutic option. An oral drug has the advantage of patient-friendly
prolonged administration in contrast to drugs that can only be applied during
vitrectomy, on condition that the drug reaches the target site. We tested whether
dabigatran reaches the vitreous and subretinal fluid (SRF) after a single oral
dose of dabigatran. METHODS: Twenty-eight patients with a retinal detachment
received a single dose of 220 mg dabigatran etexilate 2-8 hr prior to surgery.
During surgery, we took a blood sample and a vitreous or subretinal fluid sample.
The concentration of dabigatran was measured using liquid chromatography-tandem
mass spectrometry (LC-MS/MS). RESULTS: The dabigatran concentration between 2 and
9 hr after administration was higher in SRF than in vitreous (max 8.5 and 3.8
ng/ml). Corresponding plasma concentrations ranged from 15 to 225 ng/ml. There
was a significant relationship between SRF levels and plasma levels (rs = 0.68,
p = 0.014); the levels in vitreous fluid showed no such relationship (rs = 0.20,
p = 0.48). In addition, we measured the vitreous concentration of a non-study
patient using 150 mg dabigatran twice daily. The concentration was approximately
10 times higher than after a single dosage (25.8 ng/ml). CONCLUSION: We
demonstrate that oral intake of dabigatran, a candidate drug to modulate PVR,
results in potentially relevant intraocular concentrations. We suggest that
repeated dosing may lead to higher concentrations, but this should be further
explored.
PMID- 27496338
TI - Neural correlates of naturalistic social cognition: brain-behavior relationships
in healthy adults.
AB - Being able to infer the thoughts, feelings and intentions of those around us is
indispensable in order to function in a social world. Despite growing interest in
social cognition and its neural underpinnings, the factors that contribute to
successful mental state attribution remain unclear. Current knowledge is limited
because the most widely used tasks suffer from two main constraints: (i) They
fail to capture individual variability due to ceiling effects and (ii) they use
highly simplistic, often artificial stimuli inapt to mirror real-world socio
cognitive demands. In the present study, we address these problems by employing
complex depictions of naturalistic social interactions that vary in both valence
(positive vs negative) and ambiguity (high vs low). Thirty-eight healthy
participants (20 female) made mental state judgments while brain responses were
obtained using functional magnetic resonance imaging (fMRI). Accuracy varied
based on valence and ambiguity conditions and women were more accurate than men
with highly ambiguous social stimuli. Activity of the orbitofrontal cortex
predicted performance in the high ambiguity condition. The results shed light on
subtle differences in mentalizing abilities and associated neural activity.
PMID- 27496340
TI - A transcriptional blueprint for a spiral-cleaving embryo.
AB - BACKGROUND: The spiral cleavage mode of early development is utilized in over one
third of all animal phyla and generates embryonic cells of different size,
position, and fate through a conserved set of stereotypic and invariant
asymmetric cell divisions. Despite the widespread use of spiral cleavage,
regulatory and molecular features for any spiral-cleaving embryo are largely
uncharted. To address this gap we use RNA-sequencing on the spiralian model
Platynereis dumerilii to capture and quantify the first complete genome-wide
transcriptional landscape of early spiral cleavage. RESULTS: RNA-sequencing
datasets from seven stages in early Platynereis development, from the zygote to
the protrochophore, are described here including the de novo assembly and
annotation of ~17,200 Platynereis genes. Depth and quality of the RNA-sequencing
datasets allow the identification of the temporal onset and level of
transcription for each annotated gene, even if the expression is restricted to a
single cell. Over 4000 transcripts are maternally contributed and cleared by the
end of the early spiral cleavage phase. Small early waves of zygotic expression
are followed by major waves of thousands of genes, demarcating the maternal to
zygotic transition shortly after the completion of spiral cleavages in this
annelid species. CONCLUSIONS: Our comprehensive stage-specific transcriptional
analysis of early embryonic stages in Platynereis elucidates the regulatory
genome during early spiral embryogenesis and defines the maternal to zygotic
transition in Platynereis embryos. This transcriptome assembly provides the first
systems-level view of the transcriptional and regulatory landscape for a spiral
cleaving embryo.
PMID- 27496341
TI - Long noncoding RNA HULC promotes colorectal carcinoma progression through
epigenetically repressing NKD2 expression.
AB - Recently, long noncoding RNAs (lncRNAs) have been emerged as crucial regulators
of human diseases and prognostic markers in numerous of cancers, including
colorectal carcinoma (CRC). Here, we identified an oncogenetic lncRNA HULC, which
may promote colorectal tumorigenesis. HULC has been found to be up-regulated and
acts as oncogene in gastric cancer and hepatocellular carcinoma, but its
expression pattern, biological function and underlying mechanism in CRC is still
undetermined. Here, we reported that HULC expression is also over-expressed in
CRC, and its increased level is associated with poor prognosis and shorter
survival. Knockdown of HULC impaired CRC cells proliferation, migration and
invasion, and facilitated cell apoptosis in vitro, and inhibited tumorigenicity
of CRC cells in vivo. Mechanistically, RNA immunoprecipitation (RIP) and RNA pull
down experiment demonstrated that HULC could simultaneously interact with EZH2 to
repress underlying targets NKD2 transcription. In addition, rescue experiments
determined that HULC oncogenic function is partly dependent on repressing NKD2.
Taken together, our findings expound how HULC over-expression endows an oncogenic
function in CRC.
PMID- 27496342
TI - Association of HLA-A, B, DRB1* and DQB1* alleles and haplotypes in south Indian
T2DM patients.
AB - The genes of Human Leukocyte Antigen (HLA) system are implicated in the
susceptibility of several diseases including Type 2 diabetes (T2DM). Therefore,
we aimed to investigate the association of HLA alleles with T2DM in south India.
A total of 344 patients (195 males; 149 females) and 309 controls (186 males; 123
females) were genotyped for HLA-DR/-DQ alleles. Based on predominant DR/DQ
haplotypes, 222 patients and 222 age/sex matched controls were HLA-A/-B
genotyped. HLA alleles were typed by PCR-SSP methods. Susceptible association was
observed for the alleles A*33 (OR=13.8), A*01 (OR=3.69), A*02 (OR=2.91), B*07
(OR=4.12), DRB1*11 (OR=2.23), DRB1*04 (OR=1.51), DRB1*03 (OR=1.90) and DQB1*02
(OR=1.49). Protective association was observed for the alleles A*11 (OR=0.59),
A*68 (OR=0.68), B*40 (OR=0.50), B*54 (OR=0.42), B*57 (OR=0.31), B*51 (OR=0.29)
and DRB1*10 (OR=0.45). Gender stratified analysis too confirmed many of these
associations. Predominant susceptible haplotypes were A*33-B*40 (OR=10.27), A*01
B*07 (OR=4.97), A*02-B*07 (OR=6.50), DRB1*03-DQB1*05 (OR=1.88), DRB1*03-DQB1*06
(OR=3.01), DRB1*04-DQB1*05 (2.63), A*01-B*07-DRB1*10 (OR=8.26) and A*11-B*35
DRB1*07 (OR=9.338). Haplotypes A*03-B*07 (OR=0.57; p<0.034) and DRB1*10-DQB1*05
(OR=0.57; p<0.033) were protectively associated. Further, a very strong
susceptible association was documented for four-locus haplotypes such as A*11
B*40-DRB1*15-DQB1*06 (n=15; OR=16.01; p<0.001); A*01-B*07-DRB1*10-DQB1*05 (n=8;
OR=8.26; p<0.043) and A*11-B*07-DRB1*07-DQB1*05 (n=8; OR=8.26; p<0.043). Thus, a
number of HLA alleles and haplotypes showed susceptible and protective
association(s) in T2DM patients from south India.
PMID- 27496343
TI - Apolipoprotein A5 fifteen years anniversary: Lessons from genetic epidemiology.
AB - Apolipoprotein A5 (APOA5) is a small protein, expressed predominantly in the
liver. In plasma, it is located on triglyceride rich lipoprotein particles
(chylomicrones and VLDL) and on HDL. Plasma concentration of apolipoprotein A5 is
very low, suggesting rather regulatory (activation of lipoprotein lipase, ...)
than structural function. APOA5 is an important determinant of plasma
triglyceride concentration; this effect has been confirmed both on animal models,
as well as on human studies. Minor alleles of three commonly analysed variants
within this gene (rs662799, rs3135506, rs2075291) are associated with higher
plasma TG values and increased risk of myocardial infarction, with some important
interethnic differences observed. Further roles of APOA5; determination of BMI,
diabetes and last but not least nutri- and pharmaco-genetic interactions are
suggested, but without the definitive conclusions.
PMID- 27496344
TI - Cough Suppressant and Fluoxetine in the Treatment of Pseudobulbar Affect: A Case
Report.
PMID- 27496345
TI - Statistics Commentary Series: Commentary #16-Regression Toward the Mean.
PMID- 27496346
TI - The Ten Cs of Good Clinical Care.
PMID- 27496349
TI - Fibronectin, the extracellular glue.
AB - Fibronectin is an extracellular matrix protein that is present during periods of
change within tissues. It is upregulated and necessary in a number of
developmental contexts, and it is also present during pathological progression of
tissues and during wound healing. Thus, it has been studied in a broad number of
contexts from basic science to pathology. One of the unique features of
fibronectin is its ability to specifically bind a large number of molecules
including other components of the extracellular matrix, signaling molecules, and
cell adhesion molecules. Cellular interactions with fibronectin lead to
bidirectional crosstalk that directs cell function and also leads to cell
dependent changes in the extracellular matrix. Interestingly, fibronectin exists
in a functional form composed of fibers that are nm to MUm in diameter that is
highly interwoven, and fibronectin molecules that constitute this material have a
labile molecular conformation that can be altered through binding of allosteric
partners and strain resulting from application of cell contractile forces. This
review focuses on summarizing the many binding partners for fibronectin such as
ECM proteins, growth factors, and synthetic binding partners with a particular
interest in binding partners whose adhesiveness is impacted by the molecular
conformation of the fibronectin fibers.
PMID- 27496348
TI - Dynamic changes in heparan sulfate during muscle differentiation and ageing
regulate myoblast cell fate and FGF2 signalling.
AB - Satellite cells (SCs) are skeletal muscle stem cells residing quiescent around
healthy muscle fibres. In response to injury or disease SCs activate, proliferate
and eventually differentiate and fuse to one another to form new muscle fibres,
or to existing damaged fibres to repair them. The sulfated polysaccharide heparan
sulfate (HS) is a highly variable biomolecule known to play key roles in the
regulation of cell fate decisions, though the changes that muscle HS undergoes
during SC differentiation are unknown. Here we show that the sulfation levels of
HS increase during SC differentiation; more specifically, we observe an increase
in 6-O and 2-O-sulfation in N-acetylated disaccharides. Interestingly, a specific
increase in 6-O sulfation is also observed in the heparanome of ageing muscle,
which we show leads to promotion of FGF2 signalling and satellite cell
proliferation, suggesting a role for the heparanome dynamics in age-associated
loss of quiescence. Addition of HS mimetics to differentiating SC cultures
results in differential effects: an oversulfated HS mimetic increases
differentiation and inhibits FGF2 signalling, a known major promoter of SC
proliferation and inhibitor of differentiation. In contrast, FGF2 signalling is
promoted by an N-acetylated HS mimetic, which inhibits differentiation and
promotes SC expansion. We conclude that the heparanome of SCs is dynamically
regulated during muscle differentiation and ageing, and that such changes might
account for some of the phenotypes and signalling events that are associated with
these processes.
PMID- 27496350
TI - Molecular pathology of the basement membrane zone in heritable blistering
diseases:: The paradigm of epidermolysis bullosa.
AB - Epidermolysis bullosa (EB), a phenotypically heterogeneous group of skin
fragility disorders, is characterized by blistering and erosions with
considerable morbidity and mortality. Mutations in as many as 18 distinct genes
expressed at the cutaneous basement membrane zone have been shown to be
associated with the blistering phenotype, attesting to the role of the
corresponding proteins in providing stable association of the epidermis to the
dermis through adhesion at the dermo-epidermal basement membrane zone. Thus,
different forms of EB have been highly instructive in providing information on
the physiological functions of these proteins as integral components of the
supramolecular adhesion complexes. In addition, precise information of the
underlying genes and distinct mutations in families with EB has been helpful in
subclassification of the disease with prognostic implications, as well as for
prenatal testing and preimplantation genetic diagnosis. Furthermore, knowledge of
the types of mutations is a prerequisite for application of allele-specific
treatment approaches that have been recently developed, including read-through of
premature termination codon mutations and chaperone-facilitated intracellular
transport of conformationally altered proteins to proper physiologic subcellular
location. Collectively, EB serves as a paradigm of heritable skin diseases in
which significant progress has been made in identifying the underlying genetic
bases and associated aberrant pathways leading from mutations to the phenotype,
thus allowing application of precision medicine for this, currently intractable
group of diseases.
PMID- 27496347
TI - Basement membranes and autoimmune diseases.
AB - Basement membrane components are targets of autoimmune attack in diverse diseases
that destroy kidneys, lungs, skin, mucous membranes, joints, and other organs in
man. Epitopes on collagen and laminin, in particular, are targeted by
autoantibodies and T cells in anti-glomerular basement membrane
glomerulonephritis, Goodpasture's disease, rheumatoid arthritis, post-lung
transplant bronchiolitis obliterans syndrome, and multiple autoimmune dermatoses.
This review examines major diseases linked to basement membrane autoreactivity,
with a focus on investigations in patients and animal models that advance our
understanding of disease pathogenesis. Autoimmunity to glomerular basement
membrane type IV is discussed in depth as a prototypic organ-specific autoimmune
disease yielding novel insights into the complexity of anti-basement membrane
immunity and the roles of genetic and environmental susceptibility.
PMID- 27496351
TI - Does grafting of the tuberosities improve the functional outcomes of proximal
humeral fractures treated with reverse shoulder arthroplasty?
AB - BACKGROUND: Functional outcomes of reverse total shoulder arthroplasty (rTSA) can
be improved by fixation of the tuberosities. This study compares clinical and
radiologic results of patients with comminuted proximal humeral fractures treated
with rTSA, with and without autologous grafting. METHODS: Thirty-three patients
with proximal humeral fractures were treated with rTSA and tuberosity fixation.
In 18 patients (group I; mean age, 75 years), tuberosity fixation was augmented
with autografting; in 15 patients (group II; mean age, 71 years), graft
augmentation was not used. The mean follow-up was 16.7 (range, 12-24) months in
group I and 16.8 (range, 12-25) months in group II. RESULTS: Radiologic
tuberosity union was achieved in 14 of 18 (77.8%) patients who underwent
autograft augmentation and in 6 of 15 (40.0%) patients treated without
autografting. The mean American Shoulder and Elbow Surgeons (ASES) score was 69.6
+/- 13.0 in group I and 51.0 +/- 20.0 in group II. The mean Disabilities of the
Arm, Shoulder, and Hand (DASH) score was 31.9 +/- 24.0 in group I and 58.2 +/-
24.6 in group II. A significant difference was detected between groups for ASES
and DASH scores. Among shoulder range of motion measures, only forward flexion
differed significantly between groups I and II (124 degrees +/- 23 degrees vs.
98 degrees +/- 30 degrees , respectively). External rotation muscle strength was
significantly higher in group I (3.36 +/- 1.46 kg) than in group II (2.39 +/-
2.00 kg). CONCLUSION: In the treatment of complex proximal humeral fractures in
elderly patients by rTSA, cancellous block autograft augmentation can increase
the rate of tuberosity union and improve functional outcomes.
PMID- 27496352
TI - Initial medical management of rotator cuff tears: a demographic analysis of
surgical and nonsurgical treatment in the United States Medicare population.
AB - BACKGROUND: Rotator cuff tears have a lifetime incidence between 25% and 40% in
the United States, but optimum treatment strategies and protocol have not yet
been widely accepted. This study evaluated the proportions of patients treated
with nonoperative and operative modalities and how this proportion has changed
during an 8-year period (2005-2012) among patients with Medicare. METHODS: Using
the PearlDiver patient record database, we identified Medicare patients having
been diagnosed with a rotator cuff tear. These patients were then stratified on
the basis of treatment with physical therapy, subacromial/glenohumeral injection,
or rotator cuff repair. We analyzed the data in regard to standard demographic
information, comorbidities, and the Charlson Comorbidity Index. RESULTS: During
the study period, 878,049 patients were identified and 397,116 patients had
rotator cuff repair. The proportion of patients treated initially with physical
therapy dropped from 30.0% in 2005 to 13.2% in 2012, and the
subacromial/glenohumeral injection proportion decreased from 6.00% to 4.19% (P <
.001). The proportion of patients who had rotator cuff repair increased from
33.8% to 40.4% from 2005 to 2012 (P < .001). Charlson Comorbidity Indexes were
significantly lower in operative patients compared with each nonoperative
treatment examined. DISCUSSION: This analysis demonstrates a significant decrease
in the initial trial of nonoperative treatment and an increase in the rate of
surgery. Patients undergoing rotator cuff repair had fewer comorbidities than
those undergoing nonoperative treatments. It also demonstrates that patients who
had a trial of injection had a higher incidence of eventual rotator cuff repair
compared with the patients with an initial trial of physical therapy.
PMID- 27496353
TI - Intermediate-term outcome of hemiarthroplasty for comminuted proximal humerus
fractures.
AB - BACKGROUND: The purpose of this study was to evaluate the outcome of
hemiarthroplasty for comminuted proximal humerus fractures and to verify the risk
factors for functional and radiologic outcomes. MATERIALS AND METHODS: We treated
29 comminuted proximal humerus fractures by hemiarthroplasty with a low-profile
prosthesis and a bone block graft, with an average follow-up period of 53.9 (24
119) months. The patients' mean age at surgery was 71.7 (52-85) years. We
evaluated visual analog scale (VAS) scores for pain and satisfaction, active
range of motion, modified University of California-Los Angeles (UCLA) score, and
shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score.
Radiographs were checked for stem position, loosening, and tuberosity union. The
statistical evaluation was conducted to compare 2 demographics. RESULTS: The mean
VAS score was 2.1 (0-5) for pain and 8.0 (4-10) for satisfaction. Mean active
forward flexion was 125 degrees (90 degrees -170 degrees ); external rotation,
42 degrees (25 degrees -70 degrees ); and internal rotation, at T11 (T7-L2). The
mean modified UCLA score was 20 (12-30), and the mean QuickDASH score was 25 (12
38). All stems were stable without any loosening. All tuberosities were united
except 2 tuberosity absorptions. DISCUSSION: Patients older than 70 years and
patients with chronic debilitating disease, >5-mm displacement of the prosthetic
head from the glenoid, and a critical shoulder angle of >38 degrees showed
significantly poorer clinical outcome. CONCLUSION: Low-profile hemiarthroplasty
with bone block graft had unique advantages for tuberosity union. During surgery,
good prosthetic positioning with respect to the anatomic axis of the glenoid and
critical shoulder angle (>38 degrees ) were essential. However, age (>70 years)
and systemic comorbidity showed poor clinical outcome. These factors should be
considered in standardizing the clinical results.
PMID- 27496354
TI - Complications associated with arthroscopic rotator cuff tear repair: definition
of a core event set by Delphi consensus process.
AB - BACKGROUND: The literature does not consistently report on complications
associated with arthroscopic rotator cuff repair (ARCR). Valid comparison of the
occurrence of complications between ARCR interventions requires standardization.
This project was implemented to define a core set of negative (untoward) events
associated with ARCR along with their terms and definitions, which should be
systematically documented and reported in routine care and clinical research.
MATERIALS AND METHODS: A Delphi consensus process was applied. An international
panel of experienced shoulder surgeons was nominated through professional
societies and personal contacts. On the basis of a systematic review of terms and
definitions, an organized list of relevant events associated with ARCR was
developed and reviewed by panel members. Between each survey, all comments and
suggestions were considered to revise the proposed core set, including local
event groups along with definitions, specifications, and timing of occurrence.
Consensus was defined as at least two-thirds agreement. RESULTS: Three successive
online surveys were implemented involving 84 surgeons. Consensus with over 86%
agreement was reached for a core list of local events including 3 intraoperative
event groups (device, osteochondral, and soft tissue) and 9 postoperative event
groups (device, osteochondral, pain, rotator cuff, surgical-site infection,
peripheral neurologic, vascular, superficial soft tissue, and deep soft tissue).
Experts agreed on a period for documentation of each event or group of events
ranging from 3 to 24 months after ARCR. CONCLUSION: A structured core set of
local events associated with ARCR has been developed by international consensus.
Further evaluation and validation in the context of clinical studies are
required.
PMID- 27496355
TI - Validated programmed cell death ligand 1 immunohistochemistry assays (E1L3N and
SP142) reveal similar immune cell staining patterns in melanoma when using the
same sensitive detection system.
AB - AIMS: Tumour cell and/or immune cell programmed cell death ligand 1 (PD-L1)
expression is considered as a potential biomarker for anti-PD1 and anti-PD-L1
immunotherapy. Currently, different PD-L1 assays are used. This study aims to
compare the staining patterns of two PD-L1 antibody clones in melanoma metastases
and correlate them with PD-L1 mRNA expression. METHODS AND RESULTS: The
immunohistochemistry assays were optimized and validated independently on a
Ventana Benchmark Ultra (Ventana Medical Systems Inc., Tucson, AZ, USA) (E1L3N)
and XT (SP142), using the same detection system. In total, 46 melanoma metastases
were stained with both validated immunohistochemistry assays. Stained slides were
digitized for qualitative and semi-quantitative evaluation; done by pathologist
and semi-automated software analysis. A subset of 21 melanoma metastases was
selected for quantification of the PD-L1 mRNA expression. Accuracy and precision
criteria were met for both assays. PD-L1 protein and mRNA expression showed
remarkably good Spearman's coefficients of 0.90 (E1L3N) and 0.87 (SP142). Despite
the remarkable correlation between both PD-L1 assays in expression patterns and
quantification values (rho > 0.90), E1L3N showed significantly more tumour cell
staining than SP142. CONCLUSIONS: E1L3N and SP142 IHC assays were optimized and
validated successfully and independently for sensitive and accurate PD-L1
detection. Concordance was best for immune cell scoring, while E1L3N tended to
detect more tumour cells. Determination of the clinically relevant cut-off values
for immune cell versus tumour cell detection requires further research.
PMID- 27496356
TI - Avoiding costly hospitalisation at end of life: findings from a specialist
palliative care pilot in residential care for older adults.
AB - OBJECTIVES: Specialist palliative care is not a standardised component of service
delivery in nursing home care in Australia. Specialist palliative care services
can increase rates of advance care planning, decrease hospital admissions and
improve symptom management in such facilities. New approaches are required to
support nursing home residents in avoiding unnecessary hospitalisation and
improving rates of dying in documented preferred place of death. This study
examined whether the addition of a proactive model of specialist palliative care
reduced resident transfer to the acute care setting, and achieved a reduction in
hospital deaths. METHODS: A quasi-experimental design was adopted, with
participants at 4 residential care facilities. The intervention involved a
palliative care nurse practitioner leading 'Palliative Care Needs Rounds' to
support clinical decision-making, education and training. Participants were
matched with historical decedents using propensity scores based on age, sex,
primary diagnosis, comorbidities and the Aged Care Funding Instrument rating.
Outcome measures included participants' hospitalisation in the past 3 months of
life and the location of death. RESULTS: The data demonstrate that the
intervention is associated with a substantial reduction in the length of hospital
stays and a lower incidence of death in the acute care setting. While rates of
hospitalisation were unchanged on average, length of admission was reduced by an
average of 3.22 days (p<0.01 and 95% CI -5.05 to -1.41), a 67% decrease in
admitted days. CONCLUSIONS: The findings have significant implications for
promoting quality outcomes through models of palliative care service delivery in
residential facilities.
PMID- 27496357
TI - Scientific Growth and Identity Development during a Postbaccalaureate Program:
Results from a Multisite Qualitative Study.
AB - This report builds upon our previous study, which described five patterns of why
college graduates join National Institutes of Health (NIH)-funded diversity
focused Postbaccalaureate Research Education Programs (PREP). A 2015 report from
the NIH showed that a high fraction of PREP participants matriculate into PhD and
MD/PhD programs. This current study reveals how participants change during PREP,
the program elements that facilitate change, and how identity as a graduate
student and future scientist develops. Data come from in-depth interviews done at
the beginning and end of PREP with 48 individuals from seven PREP programs.
Results reveal three domains of development: academics, research, and
presentation of oneself; each domain contains a developmental continuum. Key
attributes of PREP enabling development include opportunities to attend graduate
level classes and seminars; time to practice reading literature; extended lab
time with one's own project; high and explicit expectations from mentors; and
multiple opportunities to talk about science and improve communication skills.
PREP enabled participants to develop their identities as graduate students and to
anticipate being seen by others as highly prepared for PhD training. After PREP,
85% (n = 41) started the PhD or MD/PhD, making PREP an intervention approach with
great potential to broaden participation in biomedical PhD programs.
PMID- 27496358
TI - Preparing Postbaccalaureates for Entry and Success in Biomedical PhD Programs.
AB - Certain racial and ethnic groups, individuals with disabilities, and those from
low socioeconomic backgrounds remain underrepresented (UR) in the biomedical
sciences. This underrepresentation becomes more extreme at each higher education
stage. To support UR scholars during the critical transition from baccalaureate
to PhD, we established an intensive, 1-yr postbaccalaureate training program. We
hypothesized that this intervention would strengthen each participant's
competitiveness for leading PhD programs and build a foundation of skills and
self-efficacy important for success during and after graduate school. Scholar
critical analysis skills, lab technique knowledge, and Graduate Record
Examination scores all improved significantly during the program. Scholars
reported significant confidence growth in 21 of 24 categories related to success
in research careers. In 5 yr, 91% (41/45) of scholars transitioned directly into
PhD programs. Importantly, 40% (18/45) of participating postbaccalaureate
scholars had previously been declined acceptance into graduate school; however,
17/18 of these scholars directly entered competitive PhD programs following our
training program. Alumni reported they were "extremely well" prepared for
graduate school, and 95% (39/41) are currently making progress to graduation with
a PhD. In conclusion, we report a model for postbaccalaureate training that could
be replicated to increase participation and success among UR scholars in the
biomedical sciences.
PMID- 27496359
TI - Fine-Tuning Summer Research Programs to Promote Underrepresented Students'
Persistence in the STEM Pathway.
AB - Although the importance of undergraduate research experiences in preparing
students for graduate study and research careers is well documented, specific
examination of program components is needed to assess the impact of these
programs on underrepresented (UR) students. The Leadership Alliance, a consortium
of leading PhD-granting and minority-serving institutions (MSIs), has leveraged
its diverse partnership to place UR students from MSI and non-MSI institutions in
competitive research environments through its national Summer Research Early
Identification Program. Using longitudinal pre/post data collected from student
surveys, we applied social cognitive career theory as a conceptual framework to
examine how research engagement, skill development, and mentorship aspects of a
summer research program affect students' commitment to pursue research careers.
Self-reported knowledge of research skills, time engaged in research activity,
and students' understanding of and attitudes toward pursuing graduate study were
measured in relation to the classification of students' home undergraduate
institution, level of students' pre-existing research experience, and demographic
factors. Our results provide evidence of specific programmatic components that
are beneficial for UR students from varying academic and cultural backgrounds.
This study describes important aspects of summer research programs that will
contribute to students' ability to persist in science careers.
PMID- 27496360
TI - A "Scientific Diversity" Intervention to Reduce Gender Bias in a Sample of Life
Scientists.
AB - Mounting experimental evidence suggests that subtle gender biases favoring men
contribute to the underrepresentation of women in science, technology,
engineering, and mathematics (STEM), including many subfields of the life
sciences. However, there are relatively few evaluations of diversity
interventions designed to reduce gender biases within the STEM community. Because
gender biases distort the meritocratic evaluation and advancement of students,
interventions targeting instructors' biases are particularly needed. We evaluated
one such intervention, a workshop called "Scientific Diversity" that was
consistent with an established framework guiding the development of diversity
interventions designed to reduce biases and was administered to a sample of life
science instructors (N = 126) at several sessions of the National Academies
Summer Institute for Undergraduate Education held nationwide. Evidence emerged
indicating the efficacy of the "Scientific Diversity" workshop, such that
participants were more aware of gender bias, expressed less gender bias, and were
more willing to engage in actions to reduce gender bias 2 weeks after
participating in the intervention compared with 2 weeks before the intervention.
Implications for diversity interventions aimed at reducing gender bias and
broadening the participation of women in the life sciences are discussed.
PMID- 27496361
TI - Active Learning Outside the Classroom: Implementation and Outcomes of Peer-Led
Team-Learning Workshops in Introductory Biology.
AB - Study group meetings (SGMs) are voluntary-attendance peer-led team-learning
workshops that supplement introductory biology lectures at a selective liberal
arts college. While supporting all students' engagement with lecture material,
specific aims are to improve the success of underrepresented minority (URM)
students and those with weaker backgrounds in biology. Peer leaders with
experience in biology courses and training in science pedagogy facilitate work on
faculty-generated challenge problems. During the eight semesters assessed in this
study, URM students and those with less preparation attended SGMs with equal or
greater frequency than their counterparts. Most agreed that SGMs enhanced their
comprehension of biology and ability to articulate solutions. The historical
grade gap between URM and non-URM students narrowed slightly in Biology 2, but
not in other biology and science, technology, engineering, and mathematics
courses. Nonetheless, URM students taking introductory biology after program
implementation have graduated with biology majors or minors at the same rates as
non-URM students, and have enrolled in postcollege degree programs at equal or
greater rates. These results suggest that improved performance as measured by
science grade point average may not be necessary to improve the persistence of
students from underrepresented groups as life sciences majors.
PMID- 27496362
TI - Toward Inclusive STEM Classrooms: What Personal Role Do Faculty Play?
AB - Private and public policies are increasingly aimed at supporting efforts to
broaden participation of a diverse body of students in higher education.
Unfortunately, this increase in student diversity does not always occur alongside
changes in institutional culture. Unexamined biases in institutional culture can
prevent diverse students from thriving and persisting in science, technology,
engineering, and mathematics (STEM) fields. Given the daily personal interactions
that faculty have with students, we suggest that individual educators have the
opportunity, and responsibility, to improve the retention and persistence of
diverse students. However, in our experience, faculty professional development
programs often limit discussions of diversity to "comfortable" topics (such as
learning styles) and miss opportunities to explore deeper issues related to
faculty privilege, implicit bias, and cues for stereotype threat that we all
bring to the classroom. In this essay, we present a set of social science
concepts that we can extend to our STEM courses to inform our efforts at
inclusive excellence. We have recommended strategies for meaningful reflection
and professional development with respect to diversity and inclusion, and aim to
empower faculty to be change agents in their classrooms as a means to broadening
participation in STEM fields.
PMID- 27496363
TI - Precision in donor selection: Identifying ideal stem-cell donors through their T
cells.
AB - HLA-identical siblings have always been considered ideal donors for allogeneic
hematopoietic stem-cell transplantation (allo-HSCT) in the treatment of
hematologic cancers. Recent data suggest that we should rethink this paradigm. In
"High Graft CD8+ Cell Dose Predicts Improved Survival and Enables Better Donor
Selection in Allogeneic Stem-Cell Transplantation With Reduced-Intensity
Conditioning," we identified a group of stem-cell donors whose grafts contain an
optimal composition of T-cells, leading to a dramatic decrease in disease relapse
risk and an improvement in overall survival following allo-HSCT. To demonstrate
this, we analyzed the outcomes of 200 patients with hematologic malignancies who
underwent allo-HSCT after reduced-intensity conditioning (RIC). The analysis
focused on T-cell content of peripheral blood stem-cell grafts. We found that
higher graft CD8+ T-cell dose (CD8hi), a trait found only in grafts collected
from young donors, was associated with improved survival due to a reduction in
the risk for cancer relapse without a significant increase in graft-versus-host
disease (GVHD). Though not all young donors mobilized CD8hi grafts, we found that
a low CD4:CD8 ratio in the peripheral blood could identify these ideal donors
prior to transplant. The likelihood of finding CD8hi donors correlated inversely
with age, and elderly RIC transplant recipients had a low chance of receiving an
ideal graft from their similarly aged siblings. Here, we examine these findings
and their implications on choosing donors according to age and relatedness. We
also explore biological mechanisms that determine the CD4:CD8 ratio in healthy
donors.
PMID- 27496364
TI - Genetic and environmental influences on early literacy skills across school grade
contexts.
AB - Recent research suggests that the etiology of reading achievement can differ
across environmental contexts. In the US, schools are commonly assigned grades
(e.g. 'A', 'B') often interpreted to indicate school quality. This study explored
differences in the etiology of early literacy skills for students based on these
school grades. Participants included twins drawn from the Florida Twin Project on
Reading (n = 1313 pairs) aged 4 to 10 years during the 2006-07 school year. Early
literacy skills were assessed with DIBELS subtests: Oral Reading Fluency (ORF),
Nonsense Word Fluency (NWF), Initial Sound Fluency (ISF), Letter Naming Fluency
(LNF), and Phoneme Segmentation Fluency (PSF). School grade data were retrieved
from the Florida Department of Education. Multi-group analyses were conducted
separately for subsamples defined by 'A' or 'non-A' schools, controlling for
school-level socioeconomic status. Results indicated significant etiological
differences on pre-reading skills (ISF, LNF, and PSF), but not word-level reading
skills (ORF and NWF). There was a consistent trend of greater environmental
influences on pre-reading skills in non-A schools, arguably representing 'poorer'
environmental contexts than the A schools. Importantly, this is the case outside
of resources linked with school-level SES, indicating that something about the
direct environment on pre-reading skills in the non-A school context is more
variable than for A schools.
PMID- 27496365
TI - Reaction to the letter to the editor of Huang et al.
PMID- 27496367
TI - State anxiety modulates the return of fear.
AB - Current treatments for anxiety disorders are effective but limited by the high
frequency of clinical relapse. Processes underlying relapse are thought to be
experimentally modeled in fear conditioning experiments with return fear (ROF)
inductions. Thereby reinstatement-induced ROF might be considered a model to
study mechanisms underlying adversity-induced relapse. Previous studies have
reported differential ROF (i.e. specific for the danger stimulus) but also
generalized ROF (i.e. for safe and danger stimuli), but reasons for these
divergent findings are not clear yet. Hence, the response pattern (i.e.
differential or generalized) following reinstatement may be of importance for the
prediction of risk or resilience for ROF. The aim of this study was to
investigate state anxiety as a potential individual difference factor
contributing to differentiability or generalization of return of fear. Thirty-six
participants underwent instructed fear expression, extinction and ROF induction
through reinstatement while physiological (skin conductance response, fear
potentiated startle) and subjective measures of fear and US expectancy were
acquired. Our data show that, as expected, high state anxious individuals show
deficits in SCR discrimination between dangerous and safe cues after
reinstatement induced ROF (i.e. generalization) as compared to low state anxious
individuals. The ability to maintain discrimination under aversive circumstances
is negatively associated with pathological anxiety and predictive of resilient
responding while excessive generalization is a hallmark of anxiety disorders.
Therefore, we suggest that experimentally induced ROF might prove useful in
predicting relapse risk in clinical settings and might have implications for
possible interventions for relapse prevention.
PMID- 27496366
TI - Exploring Patients' Views Toward Giving Web-Based Feedback and Ratings to General
Practitioners in England: A Qualitative Descriptive Study.
AB - BACKGROUND: Patient feedback websites or doctor rating websites are increasingly
being used by patients to give feedback about their health care experiences.
There is little known about why patients in England may give Web-based feedback
and what may motivate or dissuade them from giving Web-based feedback. OBJECTIVE:
The aim of this study was to explore patients' views toward giving Web-based
feedback and ratings to general practitioners (GPs), within the context of other
feedback methods available in primary care in England, and in particular, paper
based feedback cards. METHODS: A descriptive exploratory qualitative approach
using face-to-face semistructured interviews was used in this study. Purposive
sampling was used to recruit 18 participants from different age groups in London
and Coventry. Interviews were transcribed verbatim and analyzed using applied
thematic analysis. RESULTS: Half of the participants in this study were not aware
of the opportunity to leave feedback for GPs, and there was limited awareness
about the methods available to leave feedback for a GP. The majority of
participants were not convinced that formal patient feedback was needed by GPs or
would be used by GPs for improvement, regardless of whether they gave it via a
website or on paper. Some participants said or suggested that they may leave
feedback on a website rather than on a paper-based feedback card for several
reasons: because of the ability and ease of giving it remotely; because it would
be shared with the public; and because it would be taken more seriously by GPs.
Others, however, suggested that they would not use a website to leave feedback
for the opposite reasons: because of accessibility issues; privacy and security
concerns; and because they felt feedback left on a website may be ignored.
CONCLUSIONS: Patient feedback and rating websites as they currently are will not
replace other mechanisms for patients in England to leave feedback for a GP.
Rather, they may motivate a small number of patients who have more altruistic
motives or wish to place collective pressure on a GP to give Web-based feedback.
If the National Health Service or GP practices want more patients to leave Web
based feedback, we suggest they first make patients aware that they can leave
anonymous feedback securely on a website for a GP. They can then convince them
that their feedback is needed and wanted by GPs for improvement, and that the
reviews they leave on the website will be of benefit to other patients to decide
which GP to see or which GP practice to join.
PMID- 27496368
TI - Premature Growth Plate Closure in a Ballet Dancer en Pointe.
AB - A 13-year-old ballet dancer who had been dancing en pointe (on the tips of the
toes) since 10 years presented to the clinic with a shortened right second toe.
She had no previous history of pain or trauma. She was diagnosed with premature
growth arrest of the second metatarsal head physes resulting in a shortened
metatarsal. This is the first reported case of premature growth arrest in a
ballet dancer as a result of dancing en pointe.
PMID- 27496369
TI - Two-thirds receive no bystander cardiopulmonary resuscitation: could head
rotation be the solution?
PMID- 27496371
TI - Gender identity and the politics of etiology.
PMID- 27496370
TI - Cognitive health and risk of ED revisit in underserved older adults.
AB - OBJECTIVE: The objective was to examine associations between cognitive health and
unplanned emergency department (ED) revisits 30, 60, and 90 days after the
initial visit. METHODS: Sociodemographic, clinical, and cognitive measures were
collected on 110 white and African American adults, 65 years and older, who
sought care in an inner-city ED. The information was collected via face-to-face
interviews and review of the electronic medical record. Returns to the study-site
ED 30, 60, and 90 days later were identified through a search of the electronic
medical record. RESULTS: The sample was mostly female (70.9%) and African
American (73.6%), with an average age of 75 years (SD = 7.4). About half (56.4%)
had 12 or more years of formal schooling. The overall cognitive score of 17.5 (SD
5.1) was 4.5 points less than standardized norms for persons 65 years and older.
Each 1-point increase in cognitive score was associated with 24% and 21%
decreased odds of 60-day (odds ratio [OR] = 0.76; 95% confidence interval [CI],
0.57-1.00) and 90-day revisit to the ED (OR = 0.79; 95% CI, 0.62-0.99),
respectively. Cognitive health and odds of 30-day revisit (OR = 0.96; 95% CI,
0.72-1.26) had a nonsignificant association. CONCLUSIONS: Our sample of older,
mostly female African Americans showed poorer cognitive health compared with
standardized norms. However, higher cognitive health scores were linked to lower
risk for unplanned ED revisit 60 and 90 days later. A clearer understanding of
biological and nonbiological pathways that connect cognitive health to revisit
risk in disadvantaged older populations might improve health outcomes, including
the avoidance of return trips to the ED.
PMID- 27496373
TI - Justinus Kerner and sausage poisoning: the birth of botulinum toxin.
PMID- 27496372
TI - La Moisissure et la Bacterie: Deconstructing the fable of the discovery of
penicillin by Ernest Duchesne.
AB - Ernest Duchesne (1874-1912) completed his thesis on microbial antagonism in 1897
in Lyon. His work lay unknown for fifty years, but on being brought to light led
to his being credited with having discovered penicillin prior to Alexander
Fleming. The claims surrounding Duchesne are examined here both from the strictly
microbiological perspective, and also for what they reveal about how the process
of discovery is frequently misconstrued. The combined weight of evidence
presented here militates strongly against the possibility that the species of
Penicillium that Duchesne worked with produced penicillin.
PMID- 27496374
TI - Targeting the gastrointestinal tract to treat type 2 diabetes.
AB - The rising global rates of type 2 diabetes and obesity present a significant
economic and social burden, underscoring the importance for effective and safe
therapeutic options. The success of glucagon-like-peptide-1 receptor agonists in
the treatment of type 2 diabetes, along with the potent glucose-lowering effects
of bariatric surgery, highlight the gastrointestinal tract as a potential target
for diabetes treatment. Furthermore, recent evidence suggests that the gut plays
a prominent role in the ability of metformin to lower glucose levels. As such,
the current review highlights some of the current and potential pathways in the
gut that could be targeted to improve glucose homeostasis, such as changes in
nutrient sensing, gut peptides, gut microbiota and bile acids. A better
understanding of these pathways will lay the groundwork for novel gut-targeted
antidiabetic therapies, some of which have already shown initial promise.
PMID- 27496375
TI - ALTERED PARAFOVEAL MICROVASCULATURE IN TREATMENT-NAIVE CHOROIDAL MELANOMA EYES
DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB - PURPOSE: To determine whether parafoveal microvascular changes have occurred in
choroidal melanoma eyes before radiotherapy. METHODS: A retrospective cohort
study included 30 consecutive patients with unilateral choroidal melanoma. The
microvascular structure was analyzed by optical coherence tomography angiography.
Fellow eyes served as control for affected eyes. RESULTS: Optical coherence
tomography angiography demonstrated no difference in superficial foveal avascular
zone (P = 0.316), but showed significant enlargement in deep foveal avascular
zone (P < 0.0001) in affected eyes as compared with fellow eyes. It also showed
significant decrease in superficial (P = 0.004) and deep (P = 0.0003) capillary
vascular density (CVD). In subgroup analyses, the presence of subretinal fluid
contributed to significant enlargement of deep foveal avascular zone (P < 0.0001)
as well as reduction in superficial (P = 0.0001) and deep (P = 0.001) CVD. By
linear regression, greater tumor diameter correlated with reduction in deep CVD
(y = -0.42x + 1.01, Pslope = 0.021); greater tumor thickness correlated with
reduction in both superficial (y = -0.67x + 0.24, Pslope = 0.039) and deep (y =
0.82x + 0.56, Pslope = 0.002) CVD. CONCLUSION: Optical coherence tomography
angiography documented significant enlargement of deep foveal avascular zone as
well as reduction in superficial and deep CVD in affected eyes. These findings
correlated with the presence of subretinal fluid and increasing tumor size,
suggesting that tumor-related factors contribute to parafoveal microvascular
ischemia.
PMID- 27496377
TI - Should we consider devolution of "head and neck" surgery from the specialties of
oral and maxillofacial surgery; ear, nose, and throat surgery; and plastic
surgery?
PMID- 27496378
TI - Reeconstruction of a mandibular defect after bisphosphonate-related osteonecrosis
of the jaw.
AB - We describe the reconstruction of a mandible damaged by bisphosphonate-related
osteonecrosis of the jaw (BRONJ) using the simple and safe combination of a
reconstruction plate and patching with a submandibular gland.
PMID- 27496379
TI - Mst1 participates in the atherosclerosis progression through macrophage autophagy
inhibition and macrophage apoptosis enhancement.
AB - Emerging evidence favors the notion that macrophage autophagy plays a prominent
role in the pathogenesis of vulnerable plaque, suggesting the therapeutic
potential of targeting autophagy in atherosclerosis. Here ApoE(-/-) mice were
crossed with Mst1 knockout or Mst1 Tg mice to generate ApoE(-/-):Mst1(-/-) and
ApoE(-/-):Mst1Tg mice. All animals were fed high-fat-diet for 4months to induce
arterial atherosclerosis. Murine macrophage RAW264.7 cells were subjected to ox
LDL (50MUg/mL) in an effort to examine the cellular mechanisms. A significant
increase in the levels of Mst1 and p-Mst1 was observed in the aorta of ApoE(-/-)
mice. Mst1 knockout significantly reduced atherosclerotic area, decreased lipid
core area and macrophage accumulation as compared with ApoE(-/-) mice. Along the
same line, Mst1 overexpression increased plaque area, lipid core and macrophage
accumulation as compared with ApoE(-/-) mice. Mst1 deficiency significantly
increased levels of Beclin1 and LC3II, while decreased that of p62 in aortic
atherosclerosis. Moreover, in vitro data indicated that Mst1 knockdown prompted
more typical autophagosomes upon ox-LDL challenge. Mst1 knockdown also enhanced
autophagic flux as evidenced by GFP-mRFP-LC3 staining, increased LC3-II
expression and decreased p62 expression in the presence of bafilomycin A1. Mst1
knockdown decreased, while Mst1 overexpression increased macrophage apoptosis
upon ox-LDL exposure. In conclusion, Mst1 deficiency diminishes atherosclerosis
and stabilizes atherosclerotic plaques in ApoE(-/-) mice. Mst1 may participate in
atherosclerosis progression through inhibition of macrophage autophagy and
promotion of macrophage apoptosis.
PMID- 27496381
TI - Chronic Diarrhea: Diagnosis and Management.
AB - Chronic diarrhea is a common problem affecting up to 5% of the population at a
given time. Patients vary in their definition of diarrhea, citing loose stool
consistency, increased frequency, urgency of bowel movements, or incontinence as
key symptoms. Physicians have used increased frequency of defecation or increased
stool weight as major criteria and distinguish acute diarrhea, often due to self
limited, acute infections, from chronic diarrhea, which has a broader
differential diagnosis, by duration of symptoms; 4 weeks is a frequently used
cutoff. Symptom clusters and settings can be used to assess the likelihood of
particular causes of diarrhea. Irritable bowel syndrome can be distinguished from
some other causes of chronic diarrhea by the presence of pain that peaks before
defecation, is relieved by defecation, and is associated with changes in stool
form or frequency (Rome criteria). Patients with chronic diarrhea usually need
some evaluation, but history and physical examination may be sufficient to direct
therapy in some. For example, diet, medications, and surgery or radiation therapy
can be important causes of chronic diarrhea that can be suspected on the basis of
history alone. Testing is indicated when alarm features are present, when there
is no obvious cause evident, or the differential diagnosis needs further
delineation. Testing of blood and stool, endoscopy, imaging studies, histology,
and physiological testing all have roles to play but are not all needed in every
patient. Categorizing patients after limited testing may allow more directed
testing and more rapid diagnosis. Empiric antidiarrheal therapy can be used to
mitigate symptoms in most patients for whom a specific treatment is not
available.
PMID- 27496380
TI - Inhibition of soluble epoxide hydrolase alleviated atherosclerosis by reducing
monocyte infiltration in Ldlr(-/-) mice.
AB - RATIONALE: Circulating monocytes play pivotal roles in chronic inflammatory
diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are
known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide
hydrolase (sEH). OBJECTIVE: We aimed to investigate the effect of sEH inhibition
in atherogenesis. METHODS AND RESULTS: Mice with low-density lipoprotein receptor
deficiency (Ldlr(-/-)) with or without sEH inhibitor, and Ldlr/sEH double
knockout (DK) mice were fed a Western-type diet (WTD) for 6weeks to induce
arteriosclerosis. Both sEH inhibition and gene depletion decreased the WTD
induced hyperlipidemia, plaque area and macrophage infiltration in mice arterial
wall. Ly6C(hi) infiltration of monocytes remained similar in blood, spleen and
bone marrow of DK mice, but was decreased in aortic lesions. To further assess
the role of sEH or EETs in monocyte/macrophage infiltration in atherogenesis, we
transplanted DK bone marrow into Ldlr(-/-) recipients, and then fed mice the WTD.
Aortic lesions and Ly6C(hi) monocyte infiltration were reduced in mice with
transplanted bone marrow of DK mice without diminishing the cholesterol level.
Furthermore, sEH inhibition or gene depletion increased the ratio of EETs/DHETs
and diminished the expression of P-selectin glycoprotein ligand 1 (PSGL-1) in
mice peripheral-blood mononuclear cells. Monocyte adhesion to P-selectin and to
tumor necrosis factor alpha-activated endothelial cells was also diminished by
sEH inhibition. CONCLUSION: sEH inhibition and gene depletion attenuated
atherosclerosis in mice by decreasing the infiltration of monocytes into the
artery wall. EET and PSGL-1 may play pivotal roles in monocyte/macrophage
infiltration and atherogenesis.
PMID- 27496382
TI - Consumer quality use of medicines: An important element in public health.
PMID- 27496383
TI - Transcriptomic/proteomic identification of allergens in the mite Tyrophagus
putrescentiae.
AB - While a number of allergens from house dust mites have been described, much
remains to be discovered about allergens from storage mites. Here, next
generation sequencing was combined with MS/MS shotgun proteomics to identify
proteins, especially potential allergens from Tyrophagus putrescentiae, commonly
found in stored food products, especially flour. cDNAs of suspected allergens
were cloned and expressed from bacterial cells, and recombinant allergens were
tested for binding to IgE in sera from T. putrescentiae-sensitive patients. These
analyses identified three previously uncharacterized allergens, Tyr p 28, Tyr p
35, and Tyr p 36, which have been officially assigned by the WHO/IUIS Allergen
Nomenclature Sub-committee. Recombinant proteins rTyr p 28, rTyr p 35, and rTyr p
36 bound with 47.1%, 82.4%, and 70.6% of T. putrescentiae-sensitive sera. We
provide here a new method to identify allergens by the combination of
transcriptomic and proteomic approaches.
PMID- 27496384
TI - Study of the adaptability of preformed orthodontic archwires to the average
dental arch form of a Moroccan population.
AB - INTRODUCTION: The aim of this study is to determine which commercially available
preformed archwires offer a good fit with the average dental arch form of our
sample. MATERIALS AND METHOD: We measured the dental arch parameters of sample 1
comprising 30 dental models and compared them with the dimensions of 25 archwires
(sample 2) offered for sale by orthodontic suppliers. RESULTS AND DISCUSSION: Of
the 25 archwires tested, 10 correspond perfectly to the average dental arch form
of our sample at canine and molar level (mean+/-1SD) and would be suitable for
cases where the treatment plan involves no expansion. In addition, 3 archwires
have a shape that is slightly wider than the average arch form in the sample and
could be used for cases in which the treatment plan includes no extractions but
simply a slight expansion.
PMID- 27496385
TI - [Not Available].
PMID- 27496386
TI - Orthopedic treatment of Class III malocclusions using skeletal anchorage: A
bibliographical review.
AB - AIM: To summarize scientific articles relating to orthopedic treatment using
skeletal anchorage for Class III malocclusions in 2016. MATERIALS AND METHODS:
Exhaustive bibliographical research on PubMed with the following keywords "bone
OR skeletal-anchored maxillary protraction". RESULTS: Twenty-one articles were
noted between March 2008 and August 2015. Eleven were original articles with
clinical series. Two reviews of the literature, two technical, two focus
articles, three clinical cases and one animal study were also published.
DISCUSSION: This is the first genuinely orthopedic technique for this indication,
and it may in the medium term avoid recourse to a surgical-orthodontic protocol.
However, its use is compromised by the ignorance of practitioners and operators,
patient refusal to accept general anesthesia and less-than-perfect materials.
PMID- 27496387
TI - [Not Available].
PMID- 27496388
TI - Enforcement of the Emergency Medical Treatment and Labor Act, 2005 to 2014.
AB - STUDY OBJECTIVE: We determine the incidence of and trends in enforcement of the
Emergency Medical Treatment and Labor Act (EMTALA) during the past decade.
METHODS: We obtained a comprehensive list of all EMTALA investigations conducted
between 2005 and 2014 directly from the Centers for Medicare & Medicaid Services
(CMS) through a Freedom of Information Act request. Characteristics of EMTALA
investigations and resulting citation for violations during the study period are
described. RESULTS: Between 2005 and 2014, there were 4,772 investigations, of
which 2,118 (44%) resulted in citations for EMTALA deficiencies at 1,498 (62%) of
2,417 hospitals investigated. Investigations were conducted at 43% of hospitals
with CMS provider agreements, and citations issued at 27%. On average, 9% of
hospitals were investigated and 4.3% were cited for EMTALA violation annually.
The proportion of hospitals subject to EMTALA investigation decreased from 10.8%
to 7.2%, and citations from 5.3% to 3.2%, between 2005 and 2014. There were 3.9
EMTALA investigations and 1.7 citations per million emergency department (ED)
visits during the study period. CONCLUSION: We report the first national
estimates of EMTALA enforcement activities in more than a decade. Although EMTALA
investigations and citations were common at the hospital level, they were rare at
the ED-visit level. CMS actively pursued EMTALA investigations and issued
citations throughout the study period, with half of hospitals subject to EMTALA
investigations and a quarter receiving a citation for EMTALA violation, although
there was a declining trend in enforcement. Further investigation is needed to
determine the effect of EMTALA on access to or quality of emergency care.
PMID- 27496389
TI - Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine
Kinase EGFR.
AB - Targeting acquired drug resistance represents the major challenge in the
treatment of EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we describe
the structure-based design, synthesis, and biological evaluation of a novel class
of covalent EGFR inhibitors that exhibit excellent inhibition of EGFR-mutant drug
resistant cells. Protein X-ray crystallography combined with detailed kinetic
studies led to a deeper understanding of the mode of inhibition of EGFR-T790M and
provided insight into the key principles for effective inhibition of the recently
discovered tertiary mutation at EGFR-C797S.
PMID- 27496391
TI - Charles Desmond Ross Pengelly.
PMID- 27496390
TI - Association Between Travel Distance and Choice of Treatment for Prostate Cancer:
Does Geography Reduce Patient Choice?
AB - OBJECTIVE: To determine whether the distance between a prostate cancer patient's
home and treatment facility was related to the choice of treatment received among
those opting for surgery or radiation. METHODS AND MATERIALS: We identified
222,804 patients diagnosed with National Comprehensive Cancer Network low-,
intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy
(surgery or radiation alone, with or without hormone therapy) using the National
Cancer Database. We used multivariable logistic regression to determine whether
the choice of radiation therapy vs radical prostatectomy varied by distance among
patients living in rural and urban areas. Analyses were adjusted for geographic
location within the United States, age, race, Charlson/Deyo comorbidity score,
year of diagnosis, income quartile, education quartile, Gleason score, prostate
specific antigen level, and T stage. RESULTS: Patients living in urban or rural
areas were less likely to receive radiation compared with surgery if they lived
farther from the treatment facility. Among urban patients living <=5 miles from
the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and
33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001
in all cases). Similarly, rural patients were less likely to receive radiation
the farther they lived from the treatment facility (<=25 miles: 62.3%; 25-50
miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These
trends were also present when each risk group was analyzed separately.
CONCLUSION: Patients with prostate cancer in both urban and rural settings were
less likely to receive radiation therapy rather than surgery the farther away
they lived from a treatment center. These findings raise the possibility that the
geographic availability of radiation treatment centers may be an important
determinant of whether patients are able to choose radiation rather than surgery
for localized prostate cancer.
PMID- 27496392
TI - Health professional advice, use of medications and smoking cessation: A
population-based prospective cohort study.
AB - INTRODUCTION: The mediating role of cessation medications in the association
between health professional advice and quitting behaviors is unclear. METHODS:
Data were from the Ontario Tobacco Survey longitudinal study, collected between
July 2005 and June 2011 in Ontario, Canada. The analytic sample included 3437
baseline smokers who were seen by health professionals during follow-up. Logistic
regression with generalized estimating equations and mediation analysis
techniques were used to examine the impact of advice and medications on quitting
outcomes (making a quit attempt, short-term quitting 1-6months and long-term
quitting>6months). RESULTS: Those who received advice to quit smoking were more
likely to use cessation medications than those who did not receive advice (21%
vs. 13%, P<0.001). Receiving advice was associated with making a quit attempt
(adjusted odds ratio (OR) 1.25, 95% confidence interval (CI) 1.10-1.41) and long
term quitting (adjusted OR 1.49, 95% CI 1.10-2.02), but not with short-term
quitting. Use of cessation medications was associated with making a quit attempt
(adjusted OR 11.83, 95% CI 9.93-14.08), short-term quitting (adjusted OR 3.69,
95% CI 2.90-4.68), and long-term quitting (adjusted OR 2.73, 95% CI 1.95-3.82).
Using prescription medications was associated with a higher likelihood of
quitting short-term (adjusted OR 2.43, 95% CI 2.59-3.74) and long-term (adjusted
OR 2.27, 95% CI 1.23-4.17) than using NRT. Use of cessation medications was a
significant mediator in the pathway from receiving advice to quitting.
CONCLUSION: Health professionals should advise smokers to quit and encourage them
to use cessation medications, especially prescription medications when trying to
quit.
PMID- 27496393
TI - Smoking cessation and receipt of cessation advice from health professionals among
older smokers in Taiwan.
AB - OBJECTIVES: To examine the prevalence and correlates of smoking cessation and
receiving professional cessation advice among older smokers in Taiwan. METHODS:
Cross-sectional data from the 2008-2010 and 2012 Taiwan Adult Smoking Behavior
Survey was used to form a sample of 4081 recent active smokers aged 50+,
comprising current smokers and former smokers who quit smoking within the past
12months. We examined three outcome variables: quit attempt in the past 12months,
successful cessation for at least 3months, and receipt of health professional
cessation advice. Multivariate logistic regressions were used to identify
significant correlates. RESULTS: During the study period, the annual quit attempt
rate was 41.4%, annual successful cessation rate was 4.7%, and prevalence of
receiving cession advice among smokers who visited health professionals within
the past 12months was 72.3%. After controlling for other covariates, quit
attempts were significantly higher in 2009 and positively associated with higher
education, poorer health status, smoke-free homes, and receipt of cessation
advice. Successful cessation was significantly higher in 2009, positively
associated with older age, higher income, and smoke-free homes, and negatively
associated with receiving cessation advice. Receipt of cessation advice was
significantly lower in 2010 and 2012, positively associated with male gender,
older age, and poorer health status, and negatively associated with higher
education. CONCLUSIONS: Our results suggest that targeting lower educated and
lower income subgroups, adopting effective strategies to increase voluntary smoke
free home rules, and improving professional cessation advice will have great
potential to further reduce smoking prevalence in older smokers.
PMID- 27496394
TI - Association of sugar-sweetened beverage intake frequency and asthma among U.S.
adults, 2013.
AB - OBJECTIVES: Sugar-sweetened beverage (SSB) intake among U.S. adults is associated
with obesity and type 2 diabetes. An association between SSB intake and asthma
has been shown among U.S. children and Australian adults, but scant published
information exists for U.S. adults. We examined associations between SSB intake
and current asthma among U.S. adults, and the role of obesity in this
association. METHODS: We analyzed 2013 Behavioral Risk Factor Surveillance System
data for 146,990 adults (>=18years) from 23 states and the District of Columbia.
We used multivariable logistic regression to estimate associations between
current asthma and frequency (none, <1 time/day, once/day, >=2 times/day) of SSB
intake (soda, fruit drink, sweet tea, and sports/energy drink). SSB intake was
measured using two questions. Covariates included age, sex, race/ethnicity,
education, and smoking. Obesity, based on self-reported height and weight, was
assessed as an effect modifier. RESULTS: Overall, 9.1% of adults reported current
asthma: 8.5% of adults who did not consume SSBs had current asthma vs 12.1% of
adults who consumed SSBs >=2 times/day. There was no difference in asthma
prevalence with SSB intake <1 time/day (8.7%) or once/day (8.7%). Among non-obese
adults, the odds of having current asthma were higher among those who consumed
SSBs >=2 times/day (aOR=1.66, 95%CI=1.39, 1.99) than non-SSB consumers. However,
SSB intake frequency was not associated with asthma among obese adults.
CONCLUSIONS: Frequent SSB consumption was associated with asthma among non-obese
adults. Research on asthma prevention should further consider the potential
adverse effects of high SSB intake among U.S. adults.
PMID- 27496396
TI - Giant right atrial appendage aneurysm: Diagnosis with cardiac magnetic resonance
imaging.
PMID- 27496397
TI - Corrigendum to "Cited rationale for variance in the use of primary
intraperitoneal chemotherapy following optimal cytoreduction for stage III
ovarian carcinoma at a high intraperitoneal chemotherapy utilization center"
[Gynecol. Oncol. 142 (2016) 13-18].
PMID- 27496395
TI - Unmet basic needs and health intervention effectiveness in low-income
populations.
AB - In the face of unmet basic needs, low SES adults are less likely to obtain needed
preventive health services. The study objective was to understand how these
hardships may cluster and how the effectiveness of different health-focused
interventions might vary across vulnerable population sub-groups with different
basic needs profiles. From June 2010-2012, a random sample of low-income adult
callers to Missouri 2-1-1 completed a cancer risk assessment and received up to 3
health referrals for needed services (mammography, pap testing, colonoscopy, HPV
vaccination, smoking cessation and smoke-free home policies). Participants
received either a verbal referral only (N=365), verbal referral+tailored print
reminder (N=372), or verbal referral+navigator (N=353). Participants reported
their unmet basic needs at baseline and contacts with health referrals at 1-month
post-intervention. We examined latent classes of unmet basic needs using SAS.
Logistic regression examined the association between latent classes and
contacting a health referral, by intervention condition. A 3 class solution best
fit the data. For participants with relatively more unmet needs (C2) and those
with money needs (C3), the navigator intervention was more effective than the
tailored or verbal referral only conditions in leading to health referrals
contacts. For participants with fewer unmet basic needs (C1), the tailored
intervention was as effective as the navigator intervention. The distribution and
nature of unmet basic needs in this sample of low-income adults was
heterogeneous, and those with the greatest needs benefitted most from a more
intensive navigator intervention in helping them seek needed preventive health
services.
PMID- 27496398
TI - Preface.
PMID- 27496399
TI - Evaluation of the Motivation to Consent to and to Refuse Organ Donation Among
Participants of Educational Meetings Concerning Organ Transplantation.
AB - BACKGROUND: Improvement of the consent rate for solid organ donation from
deceased donors is a key component of strategies applied in many countries aiming
to increase the availability of organs for transplantation. Attitudes toward
living and posthumous donation are favorable. Research shows that the outlook on
organ donation and the degree of the willingness to become an organ donor are
associated with a wide range of variables. The main objective of this study was
to identify factors that influence the willingness to donate organs and the
reasons for refusing consent. MATERIALS AND METHODS: The study included 191
participants (135 female and 56 male) aged 16 to 61 years (mean age 26.86 +/-
12.88). A cross-sectional study was conducted during educational meetings
concerning organ donation that was addressed to students, teachers, and nurses.
Survey tools included the Individual Questionnaire: Study of attitudes toward
transplantation, consisting of 26 closed questions (with the consent of the
Statistical Office in Krakow). RESULTS: In all, 97.4% of the respondents accepted
transplantation from living donors, and 95.8% accepted deceased donations. Of the
respondents, 78.5% agreed to posthumous life-saving organ donation. There was a
significant difference between the respondents' sex, age, social group, place of
living, and the reasons for their willingness to donate organs both posthumously
and during their lifetime, as well as reasons for refusal. CONCLUSIONS: Our
findings showed that the study group in general had favorable views on treatment
involving transplantation and declared willingness to make a posthumous organ
donation. These views vary depending on demographic variables. The education on
the subject of organ and tissue donation has a positive impact on donation and
transplantation rates.
PMID- 27496400
TI - Central Register of Objections for Deceased Donation in Poland 1996 to 2014: The
Country With an Opting-Out System.
AB - BACKGROUND: Organ, tissue, and cell procurement from deceased donors for
transplantation requires consent and authorization, documented donor's positive
acceptance, or lack of objection to donation expressed while alive (consent). It
also requires the fulfillment of other legal conditions required by law, such as
person's legal abilities to act in this field or to obtain approval for donation
(authorization). Consent to and authorization of donation from deceased donors
requires regulations at the national level. Poland developed an opting-out policy
with the Transplantation Act in 1996. The Central Register of Objections (CRO)
was introduced on November 1, 1996. The purpose of this article is a formal
analysis of all submitted objections and objection withdrawals managed by the CRO
since the introduction of the registry in 1996 until the end of 2014. MATERIALS
AND METHODS: All data collected by the CRO during 18 years of service was subject
to analysis. The objections and withdrawals of objections are summarized in the
tables, along with the age, sex, and place of residence of the registered
residents. RESULTS: By December 31, 2014, a total of 29,288 records were
registered, including 29,013 registered objections and 275 registered withdrawals
of objections; this means that 0.075% of the country's population expressed
objection to posthumous tissue and organ donation for transplantation. Legal
representatives submitted 4208 declarations (15.6% of all declarations). The
largest inflow of objections took place in 1997, the first full year of CRO
activity. CONCLUSION: CRO is an indispensable option in a country with opt-out
system as a part of organ donation authorization protocol. Number of registered
objections is extremely low, in practice, this leads to a situation where the
will of the deceased most often is obtained from his family.
PMID- 27496401
TI - Liver Donation and Transplantation in Poland: Numbers, Indicators, and Trends.
AB - We aim to provide a panorama of liver donation and transplantation in Poland,
where each year around 300 liver transplantations from deceased donors and 20
liver fragment transplantations from living donors are performed. This means
about 9 transplantations per population of 1 million. Each year, the number of
deceased donors reaches more than 500. In more than 50% of cases, livers are
used. The law allows liver procurement from living donors. Until the end of 2013,
liver fragments were recovered from 236 living donors and transplanted mainly to
pediatric recipients (n = 232). A living-donor registry was created to monitor
and assess the health condition of donors. The range of the national waiting list
and allocation is nationwide. It is managed with the use of the Web tool
www.rejestry.net. There are 2 modes of recipient referral: "urgent" and
"elective." Allocation is either patient oriented and center oriented. Disease
groups, which comprise the most frequent indications for transplantation in
adults, include the cirrhosis group (48%), in which the highest number of
procedures was performed for patients with hepatitis C virus (24%); alcohol
induced cirrhosis (14%); alcohol-induced hepatitis (8%), and hepatitis B virus
cirrhosis (7%). Among pediatric recipients, the most frequent indications were
congenital cholestatic diseases, which made up 38% of all transplantation
indications. The results of liver transplantations are collected in the national
transplant register. The 1-year graft and recipient survival with deceased donor
transplantation are 81% and 84% and with living donor transplantation 86% and
89%. The 5-year graft and recipient survival in deceased donor transplantation
are 69% and 73%, and in living donor transplantation are 80% and 83%.
PMID- 27496402
TI - Liver Transplant Registry in Poland: Web-Netted Quality Tool in Liver
Transplantation From Deceased and Living Donors.
AB - BACKGROUND: Poltransplant managed a national transplant registry with the use of
the Web tool www.rejestry.net. It collects information about all organ
transplantations in the country along with outcomes. This article presents a
formal analysis of data collected in the registry for the years 1998 to 2014.
MATERIALS AND METHODS: Results presented are actual, not extrapolated, numbers;
these were calculated only for the events for which the observation was complete,
meaning that a given term of follow-up had passed and the information on
recipient's and graft survivals were available. RESULTS: All liver transplant
procedures were registered from the years 1998 to 2014, with follow-up data
completeness of 89% to 99%. Detailed statistical descriptions of liver transplant
results were significantly better for transplants from living donors, in
comparison to deceased donors, for pediatric recipients. Results for pediatric
and adult recipients did not vary if the organ was from a deceased donor.
Elective and primary transplantations have significantly better results in
comparison to urgent and re-transplanted cases. Results depend on indications for
transplantation. Significantly better results were obtained in the case of
cholestatic diseases and cirrhosis other than hepatitis C virus. Significantly
worse results were obtained in acute liver failure, independently of etiology.
Results in the case of hepatitis C virus cirrhosis, metabolic diseases, and
neoplasms do not vary significantly. CONCLUSIONS: The strength of these findings
are based on the registry's reliability and completeness. The registry fulfills
its aims related to collecting records and monitoring graft function, and
recipient survival. The data are an important source of information, to be used
by transplantation institutions and referred to in the literature.
PMID- 27496403
TI - Knowledge About Legal Regulations Regarding Organ Transplantation Among High
School and University Students in Poland.
AB - BACKGROUND: It has been reported in many studies that although young people have
positive attitudes towards organ donation, their knowledge about transplantation
is insufficient. This study focused on knowledge about legal regulations
regarding organ transplantation in Poland. MATERIALS AND METHODS: A 59-item, self
designed questionnaire was administered to 1011 young persons from Central
Poland. Among the interviewees were 462 high school students, 184 students of the
faculty of medicine, and 365 students from other faculties. The survey was
divided into 4 parts: knowledge (basic information, maximum of 17 points;
statistics, maximum of 5 points and legal regulations - maximum of 6 points),
attitude, personal experience and general characteristics of the interviewees.
RESULTS: High school and university students received 1.45 +/- 1.24 and 1.54 +/-
1.1 (P = .26) out of a maximal score of 6 with respect to knowledge of legal
regulations. Medical students scored much higher (4.13 +/- 1.23). Only 20
respondents (including 19 medical students) answered correctly all 6 questions.
Those who were willing to donate their organs after death achieved better result
than those who did not want to donate (1.6 +/- 1.22 vs 1.34 +/- 1.1; P = .002).
Personal experiences did not influence knowledge about transplantation.
CONCLUSION: Knowledge about legal regulations regarding organ transplantation is
insufficient among young people. Structured, well-considered education programs
at various levels of school and academic education are needed to improve public
awareness and attitude.
PMID- 27496404
TI - Do Age and Religion Have an Impact on the Attitude to Organ Transplantation?
AB - BACKGROUND: Religious issues may be a significant reason for the lack of organs
for transplantation. Younger people have a more enthusiastic attitude toward
organ donation. The goal of the present study was to determine whether age and
religion affect people's attitudes to organ transplantation. METHODS: This trial
was a diagnostic poll study using an original survey questionnaire involving 1273
people living in Podlaskie Voivodeship. RESULTS: Treatment with the use of organs
from dead donors was approved by 88.3% of the respondents aged <=60 years and
70.5% of those aged >60 years; the highest number of those who opposed this
procedure occurred in the group aged >60 years (22.3%). Baptists approved of the
method more often than persons of other religions; Muslims disapproved of it more
often than others (25%). Approximately 96% of the participants, regardless of
religion, had a positive attitude toward organ transplantation, but only 81% aged
>60 years had a positive attitude toward organ donation; there were significantly
more Catholics in this group (P < .026). In the group aged >60 years, 63.8%
expressed their consent; 66.7% of them were Muslims and Baptists. Approximately
86% of persons aged <=60 years were willing to donate their own organs after
death. These people were significantly more often Catholic (P < .045).
CONCLUSIONS: Age and religion have a considerable influence on positive attitudes
toward transplantation. The majority of younger people, as well as Catholics,
approve of the removal of organs from living donors and from dead donors.
PMID- 27496405
TI - Opinions and Attitudes of University Students Concerning Organ Transplantation.
AB - INTRODUCTION: Organ donation and transplantology are receiving more and more
support and approval all over the world every year. However, there remains a
considerable and growing difference between the number of patients awaiting
transplantation and the number of donors. The aim of the work was to find out the
opinions and attitudes of university students concerning organ donation and
transplantology. MATERIAL AND METHODS: Our poll surveyed 405 students from 2
universities (Medical University of Bialystok [MU] and Bialystok University of
Technology [UT]). The research tool used in the study was an original survey
questionnaire. RESULTS: Treatment with the use of organs taken from living
persons was approved by 55.6% of the students, from dead donors, by 73.6%, and
1.2% of the participants did not approve of that way of treatment. Of the
students from the MU, 84% approved the removal of organs from close relatives
after their death; 79.5% of those from the UT approved. Of the UT students, 8%
were against the removal of organs from close relatives after their death; 4% of
MU students were against it. Of MU students 94.5%, would agree to have their own
organs removed after death; 85.3% of UT students would agree. Of MU students,
54.2% of students had informed their families about their will to have organs
removed; 29.4% of UT students had informed their families. A greater number of
medical students had a declaration of will (28.9% vs 13.2%; P < .001). The kind
of university had a significant (P = .002) influence on the students' attitudes
to transplantation. A positive attitude was displayed by 94.5% of MU students and
83.8% of UT students, whereas a negative one, by 2% of UT students and 0.5% of MU
students. CONCLUSIONS: Different degrees of knowledge and acceptance of organ
donation were manifested by university students. To a great extent, this depended
on the kind of university. MU students understood the topic and approved of the
treatment to a greater degree. A permanent educational campaign should be carried
out among young people, especially those studying at universities other than
medical.
PMID- 27496406
TI - Effect of the Second Warm Ischemia Time and Its Components on Early and Long-term
Kidney Graft Function.
AB - BACKGROUND: During kidney transplantation, the total time of organ ischemia
consists of first warm ischemia time (WIT1), cold ischemia time (CIT), and a
second WIT (WIT2). Rising graft temperature during WIT2, which comprises the
creation of vascular anastomoses, increases oxygen demand and tissue damage,
especially in the kidney tubular cells. The aim of this study was to analyze the
influence of WIT2 on early and long-term kidney graft function. METHODS: We
performed a retrospective analysis of 554 consecutive adult recipients, who
received their first kidney graft from a deceased donor between 2003 and 2013.
RESULTS: Mean WIT2 was 25.2 min. Donors' sex, age, presence of hypertension, body
mass index (BMI), and the cause of brain death showed no effect on WIT2. Weak
positive correlations were found between the duration of WIT2 and both
recipients' age (r = 0.11; P < .01) and BMI (r = 0.14; P < .01). Multivariate
regression analysis confirmed the independent influence of age (beta = 0.107 [95%
confidence interval, 0.017 to 0.197] per year; P = .02) but not BMI (P = .09).
WIT2 influenced early graft function and was significantly longer in patients
with primary graft nonfunction than in other recipients (35.3 vs 24.9 min; P <
.01). According to receiver-operating characteristic curve analysis, a WIT2 value
>26 min was predictive of primary graft nonfunction, with 64% specificity and 58%
sensitivity. No correlations were found between WIT2 and estimated glomerular
filtration rate in the long-term follow-up period. CONCLUSIONS: This study found
that WIT2 may significantly influence the early graft function. We also found
that the creation time of vascular anastomoses does not affect the long-term
kidney graft excretory function.
PMID- 27496407
TI - The Model of Postgraduate Studies for Transplant Coordinators in Poland: 500
Graduates in the Years 2007-2015.
AB - BACKGROUND: Since 2007, the Medical University of Warsaw has been organizing the
Transplant Coordinators Postgraduate Studies, which are funded by the National
Programme for the Development of Transplantation Medicine. The aim of the studies
is to recruit medical professionals for every hospital with the potential of
deceased donations. The goal of the present study was to formally evaluate the
previous 16 editions of Transplant Coordinators Postgraduate Studies by assessing
graduate profiles and analyzing the efficiency and sustainability of their
education. METHODS: Graduate profiles were determined by gathering
sociodemographic information contained in student records. Training efficiency
and sustainability were defined by assessing the actual performance of the
coordinators' functions in the hospital after taking the course. RESULTS: As of
May 2015, the number of Transplant Coordinators Postgraduate Studies graduates
totals 501. Approximately one half of the graduates (n = 248) had nursing
degrees; training was also finished by 199 physicians, and 54 individuals had
other medical education. The number of graduates per million population across
the whole country totals 13. A total of 226 of the graduates (45%) were employed
in the years 2007-2015 in hospitals as transplant coordinators; physicians (93
graduates), nurses (107 graduates) and other medical proffessionals (26
graduates). CONCLUSIONS: The academic formula of the Transplant Coordinators
Postgraduate Studies funded by public sources makes it possible to educate
practicing staff (physicians and nurses alike) for a nationwide system of donor
hospital transplant coordinators posted in >200 hospitals and maintained by a
national transplant organization.
PMID- 27496408
TI - Prostate-Specific Antigen: Nonspecific in Deceased Organ Donors.
AB - Currently, there is no clear position regarding the donation of organs from
donors with prostate carcinoma (CaP) in European countries, except Italy. The
lengthening of life expectancy increases the probability of prostate cancer among
potential organ donors. The concentration of prostate-specific antigen (PSA) >2
ng/mL at 60 years of age is related to the increasing possibility of identifying
an advanced form of CaP. In recent years in Poland, the recommendation has been
to determine tumor markers in potential donors. In the first year of the
recommendation, 10% of potential male cadaveric donors were disqualified in West
Pomerania, Poland, on the basis of elevated PSA levels (>10 ng/mL). To avoid
reduction of the actual donor pool, each potential male donor reported to the
center since January 2010 undergoes a routine histologic evaluation of the whole
prostate, regardless of the PSA level, before organ implantation. In the study
group (N = 52), histopathologic evaluation revealed 6 cases of CaP (12%). In CaP
positive group Gleason score range from 2+2 to 3+4. In CaP donors PSA level have
been noticed in range 1.79 ng/mL - 7.66 ng/mL. There was no correlation between
histologically confirmed CaP and the PSA level.
PMID- 27496409
TI - Prostate Cancer in Deceased Liver Donors.
AB - BACKGROUND: Prostate cancer is the second most common malignant tumor (13%) among
male subjects in Poland. The aim of this study was to assess the prevalence of
prostate cancer in a group of deceased liver donors. METHODS: A total of 784
liver procurement attempts from deceased donors were performed in the Department
of General, Transplant and Liver Surgery, Medical University of Warsaw, from
January 1, 2012, to April 1, 2015; 700 grafts were actually used in a liver
transplant. A retrospective analysis was performed based on these data. Among
male donors (n = 486 [62%]), there were 30 (6.2%) cases of a frozen biopsy of the
prostate performed before making the decision regarding liver graft utilization.
RESULTS: In the group of 30 donors who underwent prostate examination, 3 (10%)
were diagnosed as having prostate cancer of a moderate invasive stage. In 2 other
cases, fresh frozen section suggested prostate cancer; however, this fact was not
confirmed in routine section. liver transplantation was not performed in these
cases of suspicion of prostate cancer (5 of 30 [17%]) in the frozen biopsy
specimens. The difference between groups of donors with prostate cancer and
benign pathology of the prostate gland according to prostate-specific antigen
serum concentration (P = .578) or age (P = .730) was not statistically
significant. CONCLUSIONS: Increased prostate-specific antigen serum
concentrations without a diagnosis of prostate cancer in histopathologic
examinations should not be an independent contraindication for performing organ
transplantation. Nevertheless, for recipient safety, even when prostate cancer is
only suspected in the frozen biopsy sample, the procured organ should not be used
for transplantation.
PMID- 27496410
TI - System of Monitoring Potential Deceased Organ Donations in Over 200 Hospitals in
Poland Using a Web Tool: Implementation and Structure.
AB - BACKGROUND: In 2010 the formation of the Polish Hospitals Network of Organ
Donation Coordinators, originated by Poltransplant, began. One of the goals of
this project is to report all deaths in hospital ICUs in which a coordinator is
posted. The aim of this strategy is to monitor donation potential, following the
recruitment process of potential donors and indicating stages of that process
that may be improved to increase effective recruitment. Until the end of 2014 all
data were forwarded to Poltransplant as Excel files, but since January 1, 2015,
reporting and data collection have been are performed using web tool
www.koordynator.net. AIMS: The aim of the paper is to present the essentials in
functioning principles, structure, and usage of the www.koordynator.net system,
its technical construction, and to display good practices (know-how) tested by 1
country, for countries such as Poland, that contend with organ insufficiency.
METHODS: The application www.koordynator.net allows for remote addition of
individual records with information about deceased patients in hospital ICUs, the
forwarding of data about potential and actual organ donors, the generation of
complete reports about deceased patients in each hospital monthly, and the
introduction of historical data. SUMMARY: Introduction of a potential donation
monitoring system in 209 hospitals with transplant coordinators increases the
number of identified potential and effective actual donors due to self-assessment
analysis. Eventually, the www.koordynator.net reporting system allowed for
external evaluation by coordinators from other hospitals, regional coordinators,
and Poltransplant. The system is a modern tool that improves and increases the
quality system in the organ donation field (quality assurance program).
PMID- 27496411
TI - Effective Application of a Quality System in the Donation Process at Hospital
Level.
AB - This article describes the application of a quality system at the hospital level
at the Multidisciplinary Hospital in Warsaw-Miedzylesie in Poland. A quality
system of hospital procedures (in accordance with the ISO system 9001:2008)
regarding the donation process, from the identification of a possible donor to
the retrieval of organs, was applied there in 2014. Seven independent documents
about hospital procedures, were designed to cover the entire process of donation.
The number of donors identified increased after the application of the quality
system. The reason for this increase is, above all, the cooperation of the well
trained team of specialists who have been engaged in the process of donation for
many years, but formal procedures certainly organize the process and make it
easier.
PMID- 27496412
TI - Organ Donation From Elderly Deceased Donors and Transplantation to Elderly
Recipients in Poland: Numbers and Outcomes.
AB - The age of a donor and recipient is one medical criterion in the kidney
allocation system. The number of elderly donors and recipients is steadily
growing. The aim of the study was to retrospectively evaluate the 5-year results
of kidney transplantation from donors over 65 years of age to recipients over 60
years of age. In the years 1998 to 2010, 8526 potential deceased donation after
brain death organ donors and 8206 people (81%), who had been treated with
transplantation of kidneys were referred to the Poltransplant. The actual number
of deceased donors >65 years was 358 and <65 years was 7207. The actual 5-year
survival of a kidney transplant from donors >65 years was 59.2% (55.3% of
recipients >60 years and 60.7% of recipients <60 years of age; P < .0001) and
from donors <65 years was 75.1% (67.5% of recipients >60 years and 75.7% of
recipients <60 years; P < .0001). The actual 5-year survival of kidney recipients
from all donors >65 years was 75.6% (79.5% younger recipients vs 65.9% elderly
recipients; P < .0001). The 5-year survival of kidney recipients from all donors
<65 years was 88.1% (P < .0001); 89% younger recipients and 74.3% elderly
recipients (P < .0001). The above analysis of the material from the Polish
registry displayed significantly worse results of kidney transplantation from
donors >65 years, regardless of the age group of recipients.
PMID- 27496413
TI - Polish Guidelines on Diagnosing Brain Death in Adults vs the International
Perspective: Are We in Need of an Update?
AB - INTRODUCTION: The Polish definition of brain death originated from the original
Harvard criteria and has been revised several times. Practitioners worldwide are
required to regularly update their national guidelines on the definition of brain
death to fit the latest international research concerning this topic. AIMS: (1)
Compare current Polish guidelines on diagnosing brain death in adults with the
American, British, Australian, and New Zealand recommendations; and (2) evaluate
existing differences for the purposes of updating the Polish guidelines.
MATERIALS: Current guidelines on diagnosing brain death published by The American
Academy of Neurology (USA, 2010), the Academy of Medical Royal Colleges (United
Kingdom, 2008), the Australian and New Zealand Intensive Care Society (AU/NZ,
2013), and the Polish Ministry of Health (Poland, 2007). RESULTS: All guidelines
outline similar recommendations regarding the need for a suitable observation
period before clinical examination and for basic medical conditions and
exclusions to be evaluated before testing, the obligatory role of clinical
examination including brain stem reflexes and apnea testing, and the
nonobligatory role of ancillary tests. There is no consensus regarding: the
recommended time period of pretesting observation, the number, seniority, and
specialty of clinicians performing the testing, the role of additional exclusion
criteria, the repeatability of clinical tests, the methodology of apnea testing,
and recommended confirmatory tests. CONCLUSIONS: Current Polish guidelines on
diagnosing brain death in adults remain up-to-date in comparison to the
guidelines analyzed, though additional recommendations concerning apnea testing,
drug and toxin clearance, and medical exclusion criteria for potential brain dead
patients might be considered an important point of interest in the future.
PMID- 27496414
TI - Assessment of Donation Potential After Circulatory Death as the First Step in
Implementing and Running a Hospital Program of Organ Procurement.
AB - BACKGROUND: In Poland the potential for organ donation from donation after
circulatory death (DCD) donors is not known. This assessment will allow the
hospital to create a quality organ harvesting system from this group of donors.
AIMS: The aim of this study was to assess the DCD potential based on
retrospective analysis of hospital deaths at Hospital Infant Jesus in Warsaw.
METHODS: Documentation of 718 deceased patients from 2010 to 2014 was analyzed.
This population could be classified as potential DCD donors in IIb category. The
deceased's characteristics were analyzed while undergoing the qualification
process for DCD. The analysis was to confirm the presence or absence of factors
disqualifying kidneys from donation and transplantation. Data from particular
departments and from the entire hospital were analyzed. RESULTS: The total number
of deaths was 718. Excluding factors from the DCD donation process were found in
664 cases (92%), mainly age >60 and concomitant diseases. The rest of the
patients (n = 54.8%) did not have factors that would exclude DCD donation. Group
characteristics are given in detail. SUMMARY: The attempt to measure donation
potential was done at the Hospital of the Infant Jesus in Warsaw, a large,
multispecialty hospital with intensive organ donation and transplantation
programs. Results show a potential for DCD donation (54 potential donations over
the last 4years), which allows us to create a quality system and algorithms for
organ donation after circulation death.
PMID- 27496415
TI - A Cell Graft or a Drug? Legal and Practical Aspects of Somatic Cells Application
in Graft-Versus-Host Disease Experimental Treatment: The Polish Experience.
AB - INTRODUCTION: Allogeneic hematopoietic stem and progenitor cell (HSPC)
transplantation and organ transplantation are well-established treatments for
different conditions. Graft versus host disease (GvHD) is a major complication in
both methods. There has been a rapid increase in the application of
nonhematopoietic somatic cells, such as mesenchymal stem cells and regulatory T
cells in GvHD experimental therapy. According to current European Union (EU) law,
human cells intended for human application can be considered either as cell
grafts or as advanced therapy medicinal products (ATMPs). OBJECTIVE, MATERIALS
AND METHODS: The aim of the paper is an attempt to answer, based on GvHD
experimental treatment data as well as existing EU and Polish law, whether cells
cease to be cells (cell grafts) and becomes drugs (ATMPs); if yes, when; and what
are the consequences of such situation both for patients as well as for
physicians engaged in the treatment process in Poland. RESULTS AND DISCUSSION:
Data analysis confirmed the interest in the experimental GvHD cell therapy. In
the vast majority of analyzed cases the in vitro culture step in the cell
preparation protocols has been foreseen. Therefore, the answer to title question
was unambiguous-expanded cells are recognized in EU as ATMPs. In borderline
cases, a scientific recommendation by the Committee for Advanced Therapies (CAT)
of the European Medicines Agency (EMA) can play an important auxiliary role;
however, it is currently neither required by Polish law nor legally binding in
Poland.
PMID- 27496416
TI - National Transplants Registry in Poland: Early and Long-term Results of Organ
Transplantations in the Years 1998 to 2014.
AB - BACKGROUND: In 2006, the National Transplants Registry, administered by the
national transplant organization, was introduced in Poland for monitoring the
results of organ transplantations. Statistical analysis is published yearly in
Poltransplant Bulletin and publicly available on the website and reported to
European institutions. The Transplants Registry cooperates with another registers
functioning on-line, based on the web-net tool www.rejestry.net. We present the
formal analysis of data collected for the years 1998 to 2014. METHODS: Analysis
covered the total number of organ transplantations in every transplant center;
outcomes after 3 months and 1, 3, and 5 years; and if data were available after
10, 15, and 20 years from transplantation. Results presented are real, not
extrapolated. RESULTS: Some examples are as follows. The total number of deceased
kidney transplantations was 15,009; 1-year recipient survival was 95%, graft
survival was 88% (data completeness of 81%), 5-year recipient survival was 87%,
and graft survival was 74% (data completeness of 82%). The total number of
deceased liver transplantations was 3143; 1-year recipient survival was 84%,
graft survival was 81% (data completeness of 99%), 5-year recipient survival was
73%, and graft survival was 89% (data completeness of 99%). CONCLUSIONS: The
National Transplant Registry is an important tool for quality and safety systems
in the transplantation field on the national level. Nowadays, the Registry
efficiently and effectively fulfills its tasks related to collecting records of
all performed transplantations. Monitoring function for graft and recipient
survival is also satisfied. Collected numbers are an important and unique source
of information to be used by transplant institutions and referred to in the
literature.
PMID- 27496417
TI - Drug Susceptibility Assessment in Stenotrophomonas Maltophilia Strains Isolated
From the Blood of Organ Transplantation Recipients in a Warsaw Teaching Hospital
During 2011 to 2014.
AB - BACKGROUND: Blood infections with multidrug-resistant Gram-negative carbapenem
resistant bacilli are particularly dangerous and challenging to treat in organ
transplant recipients. Resistance to carbapenems may be acquired, for example, in
Enterobacteriaceae, Pseudomonas, or Acinetobacter spp. or innate, for example, in
Stenotrophomonas maltophilia. The purpose of this study was to analyze blood
infections caused by S maltophilia in organ transplant recipients and to compare
drug susceptibility of these bacteria and the same species isolated from the
blood of other inpatients. METHODS: A total of 26 S maltophilia strains isolated
from blood samples of 26 patients (including 14 liver or kidney transplant
recipients) hospitalized during 2011 to 2014 were evaluated in this study.
Antibiotic susceptibility was determined via E-test and disk diffusion methods.
RESULTS: Stenotrophomonas maltophilia strains isolated from blood exhibited
sensitivity to trimethoprim/sulfamethoxazole (100%), levofloxacin (96.2%),
ciprofloxacin (92.3%), ticarcillin/clavulanic acid (80.8%), and ceftazidime
(53.9%). CONCLUSIONS: Because appropriate antibiotic therapy in the case of S
maltophilia differs from the standard empirical therapy administered in the case
of most other Gram-negative bacilli, early identification of this pathogen is of
particular significance. The use of antibiotics to which this pathogen is
sensitive eliminates the infection and helps avoid graft loss.
PMID- 27496418
TI - Epidemiological and Drug-Resistance Types of Methicillin-Resistant Staphylococcus
Aureus Strains Isolated From Surgical and Transplantation Ward Patients During
2010 to 2011.
AB - BACKGROUND: The increasing prevalence of multi-drug-resistant methicillin
resistant Staphylococcus aureus (MRSA) is a substantial problem in hospitals
worldwide, especially in wards with immunocompromised patients undergoing organ
transplant. Epidemiological characteristics and antibiotic susceptibility
profiles of hospital-acquired (HA) MRSA strains isolated from
surgical/transplantation ward patients were studied. METHODS: We analyzed 26 HA
MRSA strains isolated from 22 patients hospitalized at 3 different surgical and
transplantation wards at a Warsaw clinical hospital during 2010 to 2011. Eleven
patients were MRSA-asymptomatic carriers. Strain relatedness was evaluated
through the use of multi-locus sequence typing (MLST), multi-locus variable
number tandem repeat analysis (MLVA), and random amplified polymorphic
DNA/arbitrarily primed PCR (RAPD) methods. Antibiotic susceptibility was assessed
the use of routine diagnostic methods. RESULTS: The evaluated strains belonged to
4 clonal complexes (CCs) and 4 sequence types (STs): CC30/ST36 (65.4%), CC8/ST8
(15.4%), CC5/ST1827 (11.5%), and CC1/ST1 (7.7%). Six MLVA types and 6 RAPD types
were isolated. A ciprofloxacin-, erythromycin-, and clindamycin-resistant
CC30/ST36 clone (MLVA type 1, RAPD type 1A) was isolated in all wards. The
isolated HA-MRSA strains were most often resistant to ciprofloxacin (100%),
erythromycin (96.2%), clindamycin (84.6%), and gentamycin (30.8%). CONCLUSIONS: A
ciprofloxacin-, erythromycin-, and clindamycin-resistant HA-MRSA ST36 CC30 clone,
which prevailed on transplantation wards in the years 2010 to 2011, is probably
one of the international epidemic clones named UK EMRSA-16 or USA200.
PMID- 27496419
TI - Clinical and Microbiological Evaluation of Removable Prosthetic Restorations in
Patients Treated With an Organ Transplant.
AB - BACKGROUND: Removable dentures improve function and aesthetics of masticatory
organ. Their proper scheme of use and hygiene procedures have an impact on
biofilm formation. Microorganisms in biofilm are often resistant to many
antibiotics and may pose a potential threat to patients treated with organ
transplant. The study provided for evaluation of dental prostheses hygiene
standards with reference to staphylococcal microflora in kidney transplant
recipients. METHODS: The study involved 62 patients with removable prostheses.
Thirty-seven subjects of this group had renal replacement therapy. The other 25
were volunteers with normal renal function. Medical and dental history was
collected. Denture hygiene was assessed and swab sampling for microbiological
testing were performed on the impression surface of the denture plate. RESULTS:
Denture hygiene standards and proper scheme of their use were significantly
better in patients of the control group. In both groups, significantly with
longer denture use, patient care to provide proper hygiene standards declines.
Staphylococcal strains were found in 92% patients of the study group and 84% of
the control group, 43% of which were multi-drug resistant strains. No relation
was found between patients overall health conditions as well as denture use
methods and composition of staphylococcal denture plaque. CONCLUSIONS: Overall
health conditions and denture use methods might not have an influence on
staphylococcal denture plaque composition. However, the studies conducted did not
answer the question of whether the above factors cause quantitative differences.
Multidrug-resistant staphylococcal strains inhabiting denture surface may pose a
threat to the health of kidney transplant recipients.
PMID- 27496420
TI - Evolution of Organ Transplantation in Poland 1966 to 2014: Dates and Numbers.
AB - BACKGROUND: Several events inspired us to collect data on organ transplantation
in Poland (2016: the 50th anniversary of the first transplantation and the 20th
anniversary of Polish Transplant Coordinating Center Poltransplant). The paper
aims at presenting comprehensive data on all organ transplants, beginning with
the first in 1966 (deceased kidney) until the end of 2014. METHODS: Source
documents were reports published in Poltransplant Bulletin, a website registry
managed by Poltransplant, reports by the Transplantation Council and by the
Transplantation Institute of Warsaw. A source data enabled us to establish a
preliminary report, presented for verification during the 12th Congress of the
Polish Transplantation Society. RESULTS: By the end of 2014, the total number of
organ transplants was 26,691. Kidney transplantation is the most common (total
number = 19,812). The number of living kidney transplants is low, about 50 per
year. The number of liver part transplants from living donors is relatively high,
20 to 30 annually. The program of deceased liver transplantation results in more
than 300 transplants yearly. The first heart transplantation was in 1985, but the
number of these procedures has been decreasing. No significant increase in the
number of lung transplantations was noted. CONCLUSIONS: The number of organ
transplantations from deceased donors places Poland in the middle among European
countries. The number of living donor kidney transplants is lower than in other
countries; therefore a living donor liver transplantation program belongs to
leading programs. Progress of lung transplantation has been slow. The development
is highlighted by vascularized composite tissue transplantations of the hands and
face. The strength of the report lies in its reliability and completeness.
Numbers are the unique source of information to be used and referred to in the
literature.
PMID- 27496421
TI - Dietary Intake of Vitamins in Different Options of Treatment in Chronic Kidney
Disease: Is There a Deficiency?
AB - BACKGROUND: The importance of diet in the management of kidney transplantation
(KT), as well as other treatment options of chronic kidney disease (CKD), is
generally acknowledged. However, data regarding vitamin intake are very limited.
Vitamins are essential in maintaining good nutritional status and preventing many
chronic complications. It is still not clear which treatment modality imposes the
highest risk of dietary vitamin deficiency and whether successful KT reverses
such a threat. METHODS: We performed this observational study to assess dietary
intake of vitamins in CKD patients: after successful KT, not yet dialyzed (ND),
treated with hemodialysis (HD), and with peritoneal dialysis (PD). A total of 202
patients were recruited (45 KT, 50 ND, 45 HD, and 62 PD). Vitamin intakes were
evaluated through the use of a 24-hour dietary recall and processed with the use
of a computerized database. Each record was evaluated by a skilled dietitian. In
general, vitamin intakes in all study groups were comparable, with KT and ND
groups manifesting lower risk of deficiency than HD and PD groups. RESULTS: The
content of fat-soluble vitamins in diet was insufficient, with remarkably high
prevalence of vitamin D deficiency. Mean intakes of water-soluble vitamins were
close to recommended, with the exception of folic acid, which was profoundly
deficient in all groups. CONCLUSIONS: CKD patients are at risk of inadequate
vitamin intake. Vitamin D and folic acid are universally deficient in diet. KT
patients have the most satisfactory content of vitamins in their diet, whereas HD
individuals are at highest risk of deficiency.
PMID- 27496422
TI - Assessment of the Hemostatic Parameters and Platelet Function on
Thromboelastometry and Impedance Aggregometry in Hemodialysis Patients Qualified
for Kidney Transplantation: Preliminary Report.
AB - BACKGROUND: Chronic kidney disease is one of the medical conditions that affect
hemostasis. Patients undergoing hemodialysis present both hemorrhagic and
prothrombotic tendencies. Platelet adhesion to the artificial surface of the
dialyzer's membrane, blood vessel endothelial wall disruption, and quantitative
and qualitative changes in clothing factors are thought to be causative agents of
the above-mentioned conditions. Thromboelastometry and impedance aggregometry
enable precise assessment of clot formation and platelet function abnormalities,
including changes related to chronic renal failure in patients undergoing renal
replacement therapy. METHODS: A prospective study with control group was
designed. The study group consisted of 17 adults with diagnosed chronic renal
failure undergoing hemodialysis. The control group consisted of 13 healthy
volunteers. EXTEM and FIBTEM tests in rotational thromboelastometry and TRAPtest
in impedance aggregometry analyzer were performed. RESULTS: EXTEM parameter test
results were comparable between analyzed groups, whereas FIBTEM test results were
significantly increased in the study group. Platelet aggregation as measured by
the TRAPtests was significantly decreased in patients undergoing hemodialysis.
CONCLUSIONS: In end-stage renal disease patients undergoing hemodialysis, whole
blood clot formation is not disturbed, even though platelet dysfunction occurs.
Increased fibrin clot formation reflected by FIBTEM results may compensate the
observed platelet disorders. The compilation of ROTEM and Multiplate may support
appropriate hemostatic control and decision-making during kidney transplantation.
PMID- 27496423
TI - Do Patients With End-Stage Chronic Renal Failure Treated With the Use of
Hemodialysis Have Healthy Skin? Evaluation of Skin Lesions and Basic Education
About Risk Factors for Skin Cancer in This Patient Population.
AB - BACKGROUND: Considering the increasing incidence of skin cancers in patients
after renal transplantation, evaluation of skin condition in dialysis patients,
from whom kidney transplant recipients are recruited, appears to be very
important. Particular importance is attached to the identification of such
dialysis patients in the population who require dermatologic care before
qualifying for transplantation. The objective of this study was to determine the
prevalence of skin diseases in the dialysis patient population. Education of the
patients regarding risk factors for skin cancer and the need for sun protection
was performed. METHODS: Full dermatologic examination, including dermatoscopy,
was performed on a group of 77 dialysis patients (38 women, 39 men) and a control
group of 77 healthy people (60 women, 17 men). RESULTS: Eight hemodialysis
patients had healthy skin compared with 33 people from the control group. In the
remaining hemodialysis patients, the following skin lesions were observed: 1)
inflammatory and allergic skin disorders in 17 patients; 2) bacterial, fungal,
and viral infections in 26 patients; 3) benign lesions in 39 patients; 4)
malignant skin lesions and precancerous conditions in 4 patients; and 5) other
skin changes in 63 patients. CONCLUSIONS: Skin lesions are common in the dialysis
patient population. Only 10% of the examined population had completely healthy
skin, compared with 43% of the control group. More than one-half of dialysis
patients required dermatologic care compared with one-third of healthy control
subjects.
PMID- 27496424
TI - Pathologies in Living Kidney Donors Diagnosed in the Long-Term Care System.
AB - Kidney donation should not lead to deterioration of the donor's health condition,
both during the perisurgical period and in the long term. Safety of a living
kidney donor becomes a prerequisite for his/her qualification. Detailed
diagnostic procedures are performed to exclude any abnormalities of his/her
health condition. Additionally, a long-term post-donation follow-up system for
kidney donors has been set up in Poland besides the restrictive qualification
system. Transplantation centers are obligated to provide a diagnostic procedures
for living organ donors as a part of the monitoring of their health condition and
to ensure them a medical follow-up for 10 years after the donation. A total of
141 cases of unilateral nephroureterectomy performed in 2003-2014 to obtain a
kidney for transplantation were considered. Medical files of post-donation
diagnostic or therapeutic methods and their outcomes were retrospectively
analyzed. The aim of the study was to assess the efficacy of monitoring of
donors' health condition within the framework of the long-term follow-up system
for kidney donors in the aspect of detection of the donation-independent
abnormalities.
PMID- 27496425
TI - Human Pooled Immunoglobulin as Treatment of Active Antibody-Mediated Rejection of
Transplanted Kidney.
AB - BACKGROUND: Antibody-mediated rejection (ABMR) has emerged as the leading cause
of renal graft loss. The optimal treatment protocol in ABMR remains unknown. This
study aimed to assess the efficacy of intravenous immunoglobulin (IVIG) for
treatment of ABMR in renal recipients. METHODS: Thirty-nine ABO-compatible cross
match-negative renal recipients with biopsy-proven ABMR composed the study group.
Pulses of methylprednisolone (MP) and appropriate enhancement of net state of
immunosuppression were applied in all individuals; 17/39 recipients were
administered IVIG (IVIG group); the remaining 22/39 patients, identified to be
nonadherent or unsatisfactorily immunosuppressed, were kept on the initial
treatment (MP group). Serum creatinine concentration was obtained at each of 10
intended visits, and glomerular filtration rate (GFR) was estimated with the use
of the standard Modification of Diet in Renal Disease (MDRD) formula. Generalized
linear mixed model was used for statistical analysis. RESULTS: Renal function
(modeled as linear slope of MDRD-based GFR change over time, separately for the
pre- and post-intervention periods) improved significantly in IVIG-treated
recipients. Pre-intervention slopes were -0.72 and -0.46 mL/min/mo for IVIG and
MP groups, respectively (P = NS), whereas post-intervention the slopes changed to
-0.03 and -0.47 mL/min/mo (IVIG and MP, respectively; P < .005). Within-group
changes of slopes at the time of intervention were 0.69 and -0.01 mL/min/mo in
IVIG (P < .01) and MP (P = NS) groups, respectively. The relative slope change
(pre- to post-intervention) was 0.7 mL/min/mo in favor of the IVIG group (P <
.033). None of the classic immunologic or nonimmunologic graft function
predictors influenced GFR during 12 months of follow-up. CONCLUSIONS: IVIG
improved graft function in renal recipients diagnosed with ABMR.
PMID- 27496426
TI - BICD1 and Chromosome 18 Polymorphisms Associated With Recipients' Telomere Length
Affect Kidney Allograft Function After Transplantation.
AB - BACKGROUND: Reports regarding recipient's nonmodifiable genetic factors affecting
telomerase activity and thus allograft function are lacking. Therefore the aim of
this study was to analyze the associations between recipients' rs2735940 hTERT,
rs2630578 BICD1, and rs7235755 chromosome 18 polymorphisms and kidney function
after transplantation. METHODS: The study enrolled 119 white Polish kidney
allograft recipients (64 men, 55 women; overall mean age, 47.3 +/- 14.0 y). To
identify genotypes of the studied polymorphisms, real-time polymerase chain
reaction was performed. RESULTS: There were statistically significant differences
in distribution of rs7235755 chromosome 18 polymorphism genotypes and alleles
between recipients with delayed graft function (DGF) and without DGF (P = .03).
The presence of A allele was significantly associated with higher risk of DGF
occurrence (AA + GA vs GG: OR, 3.25 [95% CI, 1.16-9.14]; P = .02; GA vs GG: OR,
4.00 [1.35-11.82]; P = .01). Analysis of the rs2630578 BICD1 gene polymorphism
genotypes revealed statistically significant differences in long-term creatinine
concentrations. The presence of C allele of this polymorphism was significantly
associated with higher creatinine concentrations 24, 36, and 18-48 months after
transplantation (GC + CC vs GG: P = .008, P = .008, and P = .01, respectively).
CONCLUSIONS: Recipients' polymorphisms of genes associated with telomere length,
BICD1 and chromosome 18, but not hTERT, affect kidney allograft early and long
term function after transplantation. There is an urgent need for explanation of
these observations in genome-wide association studies.
PMID- 27496428
TI - Enhanced Recovery After Kidney Transplantation Surgery.
AB - BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have gained
widespread recognition in general surgery, decreasing the length of hospital stay
while maintaining equivalent or lower morbidity and increased patient
satisfaction. The feasibility of the ERAS protocol has not been studied in kidney
transplantation. In this single-center retrospective case series, we describe the
outcomes of 45 consecutive deceased-donor kidney transplant recipients subjected
to a modified ERAS protocol, and we discuss the potential for future
developments. METHODS: Included in the analysis were 45 consecutive deceased
donor kidney transplant recipients from August 2014 to July 2015 in the John Paul
II Krakow Specialist Hospital, Krakow, Poland. All patients were subjected to a
modified ERAS protocol. The primary outcomes were length of hospital stay and
mortality and morbidity rates. A surrogate composite criterion for discharge was
ability to attend the transplant clinic weekly with no need for dialysis. The
secondary outcome was the rate of unplanned readmissions within the 1st 3 months
after transplantation. RESULTS: The median hospital stay was 10 days (range, 6
46). There were no deaths or acute coronary or thromboembolic events. Serious
complications requiring surgery occurred in 6.6% of recipients. Three-month graft
survival was 97.8%. The unplanned readmission rate was 8.9%. CONCLUSIONS: ERAS
protocol is feasible in deceased donor kidney transplantation and renders low
morbidity rates and reasonable readmission rate. Further reduction of the length
of the hospital stay can be expected with health care system financial policies.
PMID- 27496427
TI - Early and Long-Term Outcomes of Kidney Grafts Procured From Multiple-Organ Donors
and Kidney-Only Donors.
AB - BACKGROUND: The deceased-donor kidney pool consists of 2 different populations:
multiple-organ donors (MOD) and kidney donors alone (KDA). In MOD, more
complicated procedure and lowest priority for kidney procurement may affect graft
survival. On the other hand, poor donor status and higher comorbidity are more
frequent in KDA transplants. The aim of this study was to provide detailed
characteristics of the 2 groups of kidney donors (KDA vs MOD) in our center and
to analyze the potential influence of the donor type on the early and long-term
kidney graft function and recipient outcome. METHODS: We performed a
retrospective analysis of 729 first cadaveric kidney transplant recipients: 499
of them received the organ from MOD, 230 from KDA. RESULTS: The frequency of
delayed graft function (DGF) was higher in KDA than in MOD transplants (38.7 vs
25.1%; P < .001). Multivariate logistic regression analysis revealed that donor
age, KDA, and early acute rejection independently increased the risk of DGF
occurrence, whereas recipient age and cold ischemia time increased the risk of
primary graft nonfunction. Kidney excretory function was significantly worse in
KDA up to 10 years after transplantation. There were no differences in kidney
graft and patient survivals, frequency of proteinuria, acute rejection, and
cytomegalovirus episodes, and post-transplantation diabetes. CONCLUSIONS: (1) The
use of a kidney from KDA negatively affects early and late kidney graft function
compared with MOD. (2) The long-term kidney graft and patient survivals are not
affected by the type of organ procurement.
PMID- 27496430
TI - Influence of Body Mass on Kidney Graft Function in Patients After Kidney
Transplantation.
AB - BACKGROUND: Increasing evidence shows that body mass may play a role in
complications after kidney transplantation and influence graft and patient
survival. The aim of this study was to analyze the association between graft
function and both the body mass and adipokines (leptin, visfatin, adiponectin) in
kidney transplant recipients. METHODS: We studied 183 kidney transplant
recipients from the Department of Nephrology, Transplantology and Internal
Disease, Medical University of Gdansk. Anthropometry and body composition
examinations were performed using an electronic scale, hand grip dynamometer, and
BCM - Body Composition Monitor (Fresenius, Germany). Obesity, overweight, and
underweight were defined according to body mass index (BMI) classification. Blood
urea nitrogen, creatinine, blood morphology, lipidogram, albumin, and C-reactive
protein were measured. Estimated glomerular filtration rate (eGFR) was calculated
according to the Chronic Kidney Disease Epidemiology Collaboration formula.
Leptin, visfatin, and adiponectin were measured by ELISA methods. RESULTS:
Underweight was found in 16 (8.7%) KTR, overweight and obesity were observed in
68 (37.1%) and 26 (14.2%) patients, respectively. No relation between BMI and
eGFR in all groups was noted, but in the early period after transplantation a
correlation between BMI and creatinine and eGFR was observed. In all studied
patients (also patients in the early posttransplantation period), eGFR
significantly correlated with leptin and visfatin. Multiple regression analysis
confirmed an association between eGFR and leptin and visfatin in all studied
populations and between eGFR and BMI in the group examined shortly after
transplantation. CONCLUSIONS: Sarcopenic overweight and obesity prevail in KTR.
In the short-term but not long-term period after transplantation, worse graft
function was associated with high BMI. An association between graft function and
leptin and visfatin was noted.
PMID- 27496429
TI - Donation and Transplantation of Kidneys Harvested From Deceased Donors Over the
Age of 60 Years in the Upper Silesia Region.
AB - BACKGROUND: Population aging and shortage of organs for transplantation result in
increasing numbers of kidneys retrieved from elderly donors. The aim of this
study was to analyze donation of kidneys from donors after brain death (DBD) over
the age of 60 years (>=60), comorbidities that affect decisions on retrieval, and
early results of kidney transplantation. METHODS: Ninety-six potential DBD >=60
and 309 aged 40-59 years (40-59) reported in Upper Silesia, Poland, from 2004 to
2013 were enrolled in the study. RESULTS: DBD >60 presented a higher rate of
coexisting hypertension (53% vs 34%), limb ischemia (10% vs 1%), and past stroke
(6% vs 1%) compared with DBD 40-59 (P < .05), but no differences were observed in
serum creatinine concentration (85 vs 84 MUmol/L), coexisting coronary disease
(14% vs 6%), or diabetes (10% vs 4%). The decision of withdrawal from retrieval
was more frequent in DBD >=60 (16% vs 7%; P < .05). Twelve months after kidney
transplantation, serum creatinine concentration was higher in recipients of
kidneys from DBD >=60 compared with DBD 40-59 (169 vs 138 MUmol/L; P < .001). The
survivals of recipients (93% vs 95%) and kidney grafts (90% vs 93%) as well as
rates of proteinuria >1.0 g/24 h (6% vs 2%) did not differ between the groups.
CONCLUSIONS: A higher rate of comorbidities in potential kidney DBD >=60 results
in a lower retrieval rate in these donors. The function of kidneys harvested from
DBD >=60 12 months after transplantation is worse than those from DBD 40-59, but
still acceptable.
PMID- 27496431
TI - Renal Transplantation Using Kidneys Procured From Elderly Donors Older Than 70
Years.
AB - AIM: A major problem for the transplant society is a shortage of organs for
transplantation compared with the number of patients on the waiting list. This
study aimed to assess the results of the transplantation of kidneys procured from
older donors. PATIENTS AND METHODS: A total of 27 kidneys procured from donors
age 70 years or older were transplanted between January 1, 2010, and April 25,
2015. These represented only 4.1% of the 657 kidneys transplanted from deceased
donors during this period at the same center. RESULTS: Delayed graft function
(DGF) in the recipients of kidneys procured from donors age 70 or older occurred
in 46.1% of patients, whereas the recipients of kidneys from younger donors
showed DGF at a frequency of 32.7% (P = NS). The annual and 3-year survival rates
of kidneys in the study group were 85% and 80%, respectively, and in the control
group were 92.5% and 88.6%, respectively (P = NS). According to the Polish
National Organ Procurement Organization (Poltransplant), the annual survival rate
of a transplanted kidney in Poland stands at 89%, whereas the 3-year survival
rate is 82%. We detected no significant posttransplantation differences in the
serum creatinine concentration and in the estimated glomerular filtration rate
between the study and control groups. The donor age and donor creatinine were the
variables independently associated with DGF. CONCLUSIONS: The results of
transplantation of kidneys from elderly donors were comparable to those of
transplantation from younger donors. Kidneys harvested from elderly donors should
be used for a transplant after a preliminary assessment.
PMID- 27496432
TI - Impact of Obesity on Renal Graft Function-Analysis of Kidney Grafts From the Same
Donor.
AB - BACKGROUND: The epidemic of obesity has led to dilemmas facing all nephrologists
who care for patients with chronic kidney disease and who must make decisions
regarding whether or not the patient can undergo transplantation. The aim of the
study was to assess the outcome of transplantation among obese compared to
nonobese recipients. To minimize donor variability and bias, paired kidney
analysis was applied. MATERIALS AND METHODS: Patients with a body mass index >30
who received transplants in our unit between January 2000 and December 2010 were
selected. For the analysis, only obese transplant recipients (OTR) and their
kidney donor pairs with a body mass index <30 (nonobese transplant recipients
[NOTR]) were selected. A total of 37 pairs of patients were evaluated in terms of
the graft function, patient and graft survival, and number of complications.
RESULTS: Groups did not differ with respect to sex and comorbidities. OTR were
older than NOTR (53.1 vs 46.02 years old, P < .05). One-year patient and graft
survivals were similar (100% vs 97.29% and 100% vs 94.59% in OTR and NOTR,
respectively). There were no significant differences between OTR and NOTR with
respect to incidence of acute rejection (29.7% vs 18.9%), delayed graft function
(35.13% vs 29.72%), and mean serum creatinine and estimated glomerular filtration
rate (four-variable Modification of Diet in Renal Disease formula) assessed at
discharge and after 3, 6, and 12 months, respectively. OTR had a significantly
longer hospitalization time (25.56 vs 20.66 days; P < .05), and more often
experienced wound breakdown (32.43% vs 8.1%; P < .05) and new-onset diabetes
after transplantation (57.14% vs 6.25%; P < .05). CONCLUSIONS: Obesity did not
negatively influence patient and graft survival. Transplantation in obese
patients should not be postponed.
PMID- 27496433
TI - Outcomes in Renal Transplant Recipients With Lupus Nephritis-A Single-Center
Experience and Review of the Literature.
AB - BACKGROUND: Renal transplantation is the renal replacement therapy of choice in
patients with end-stage lupus nephritis (LN). The aim of this study was to
evaluate the early and late outcomes of renal transplantation in LN patients in a
single transplant center. PATIENTS AND METHODS: This study analyzed the clinical
data of patients who received a renal transplant (RTx) at Gdansk Transplantation
Centre between January 1999 and December 2014. RESULTS: There were 1296 RTx
performed between January 1999 and December 2014, including 21 RTx in 19 LN
patients (mean age 40 +/- 10 years, 89% female). During the follow-up period
(between 1 month and 10.5 years), 1 patient died of urosepsis and 1 of pneumonia.
Three RTx recipients with antiphospholipid syndrome lost 5 kidney allografts,
including 3 due to acute rejection (AR) during the first posttransplantation
month. Kidney allograft survival median was 64 months. Delayed graft function
(DGF) and AR were observed in 48% and 33% vs 31% and 21% of LN patients and other
RTx patients, respectively (P = .1 and P = .16 for DGF and AR, respectively). The
most common early posttransplantation complications were AR (31%) and perirenal
hematomas (29%), and late complications were urinary tract infections (75%).
Recurrence of LN in renal allograft was observed in 1 patient and was
successfully treated by increasing the basic immunosuppression. CONCLUSIONS:
Secondary antiphospholipid syndrome has a major influence on the outcomes of RTx
in LN patients. Recurrence of LN has no clinical significance.
PMID- 27496434
TI - Performance of the MDRD, CKD-EPI, and Cockcroft-Gault Formulas in Relation to
Nutritional Status in Stable Renal Transplant Recipients.
AB - BACKGROUND: Monitoring of the function of the implanted kidney in renal
transplant recipients (RTRs) is one of the superior elements of adequate
therapeutic actions. The aim of this study was to assess the conventional and
unconventional factors affecting the estimated glomerular filtration rate (eGFR)
with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault (C-G) formulas among
the RTRs. METHODS: The study included 144 RTRs (mean age 52 years). Clinical and
laboratory data were analyzed; eGFR was calculated with MDRD, CKD-EPI, and C-G
formulas. We compared the results with MDRD as a reference calculating the
percentage of reclassifications of chronic kidney disease (CKD) stages.
Nutritional status was assessed with a body composition analyzer, Tanita BC 418.
RESULTS: Multivariable linear regression analysis with MDRD and CKD-EPI formula
as a dependent variable retained the following independent predictors: hemoglobin
(Hb) (B = .365; P = .000), and red blood cell distribution width (RDW) (B =
.191; P = .024). Analysis of variance showed the existence of statistically
significant differences (all P for trend <.05) between the CKD-EPI, MDRD, and C-G
equations within the total scope of eGFR results (51.2 +/- 21.2 vs 47.5 +/- 18.7
vs 55.6 +/- 20.6, respectively) as well as in quartiles of eGFR. CONCLUSIONS: Our
data indicate that (1) with a value of eGFR >60 mL/min/1.73 m(2), the MDRD
formula shows values that are on average 11% lower than in the CKD-EPI and C-G
formulas; (2) with a value of eGFR <60 mL/min/1.73 m(2), the MDRD and CKD-EPI
formulas do not show statistically significant differences.
PMID- 27496435
TI - Living-Donor Versus Deceased-Donor Kidney Transplantation: Comparison of
Psychosocial Consequences for Recipients.
AB - INTRODUCTION: Health benefits of a living-donor kidney transplantation are
numerous and well known. There is, however, a dearth of knowledge on
postoperative quality of life among the living-donor (LD) compared to deceased
donor (DD) transplant recipients. MATERIALS AND METHODS: The study involved 89
patients after renal transplantation: 48 from LDs and 41 from DDs. Interview data
indirectly indicated the patients' health, whereas physiological parameters
directly pinpointed the patients' health and the graft function. All study
participants completed questionnaires to measure quality of life and the
specificity of emotional and cognitive functioning. RESULTS: LD kidney recipients
were younger than DD recipients (40 years vs. 49 years). LD and DD
transplantation patients were similar in health status assessed by indirect
methods (data from an interview) and direct methods (laboratory tests results).
They, however, differed in their psychosocial functioning. LD patients had a
greater sense of happiness (P < .01) and of self-efficacy (P = .07). Moreover,
these patients were more actively involved in their social lives (P < .02) and
were more satisfied with their social relationships (P = .07). LD recipients also
had a higher quality of life in terms of mental functioning (P < .01) and
satisfaction with their environments (P < .01). Additionally, there were
significant correlations between quality of life and the quality of cognitive and
emotional functioning in the group of LD recipients. The perceived impact of
health on physical and professional activity and daily routines was similar in LD
and DD groups. CONCLUSIONS: LD post-transplantation patients may derive greater
psychosocial benefits from this form of treatment. This effect is not dependent
on somatic parameters (comparable data from an interview and laboratory tests
results). This study suggests that patients should be assisted by a
multidisciplinary healthcare team, and receive continuous support from relatives
during the post-transplantation adaptation process. This facilitates the
patients' postoperative quality of life.
PMID- 27496436
TI - Prospective Assessment of Hepcidin in Relation to Delayed or Immediate Graft
Function in Patients Undergoing Kidney Transplantation.
AB - BACKGROUND: Hepcidin is a peptide hormone that regulates iron homeostasis.
Hepcidin may represent an early, predictive biomarker of acute kidney injury,
another model of ischemia-reperfusion injury. Urinary hepcidin-25 has been shown
to be elevated in patients who do not develop acute kidney injury. Creatinine is
an unreliable indicator during acute changes in kidney; therefore, the aim of the
study was to assess whether hepcidin could predict renal outcome in 31
consecutive patients undergoing kidney allograft transplantation. Serum hepcidin
was evaluated before and after 1, 3, 6, and 10 days after kidney transplantation,
using commercially available kits. Serum creatinine was assessed at the same
time. METHODS: We found a significant decrease in serum hepcidin, as early as
after 1 day after kidney transplantation. Before transplantation, serum hepcidin
was related to creatinine. In patients with delayed graft function, there was no
decrease in serum hepcidin. RESULTS: Our findings may have important implications
for the clinical treatment of patients undergoing kidney transplantation. The
"window of opportunity" is narrow in delayed graft function to distinguish
between acute rejection and calcineurin inhibitors nephrotoxicity, and time is
limited to introduce proper treatment after initiating insult. CONCLUSIONS:
Hepcidin must be investigated as a potential early marker for delayed graft
function, especially in the upcoming setting of early dialysis treatment or anti
rejection therapy and might contribute to early patient risk stratification.
PMID- 27496437
TI - HRV Influence During Renal Transplantation Procedure on Long-Term Mortality.
AB - BACKGROUND: The autonomic nervous system plays an important role in heart
function regulation. One of the most acknowledged methods for noninvasive
measurement of autonomic system activity is to determine heart rate variability
(HRV). Reduced HRV parameters-heart rate rigidity/stiffness-are an independent
prognostic factor of sudden cardiac death risk because of arrhythmia. Renal
transplantation is an important factor in HRV changes because of hemodynamic and
ion disturbances. The main purpose of this study was to determine the influence
of HRV disturbances during renal transplantation procedures on long-term
mortality in patients with chronic kidney disease. METHODS: A prospective
observation study was performed in the Department of Anesthesiology, Intensive
Care, and Acute Poisoning, Pomeranian Medical University, Szczecin, Poland. There
were 75 patients (mean age, 47 +/- 12 years; 42 men) treated with renal
transplantation between 2008 and 2010. Patients were monitored with
electrocardiographic tracing with the use of 7 electrodes in position type B. The
final stage of analysis was to determine the possible relationship between HRV
parameters during the perioperative period and the number of deaths within a 5
year follow-up. RESULTS: HRV parameters during the perioperative period of renal
transplantation and the number of deaths within a 5-year follow-up, measured by
use of the Holter method, did not differ among patients in the studied
population. CONCLUSIONS: HRV is a noninvasive and confirmed tool used for the
evaluation of autonomic function and mortality risk in patients with end-stage
renal disease. HRV parameters recorded in the perioperative period are not
optimal stratification tools for estimating the risk of cardiac deaths in
patients with end-stage renal disease.
PMID- 27496438
TI - Psychological Well-Being in Patients After Preemptive Kidney Transplantation.
AB - BACKGROUND: Preemptive kidney transplantation (PKT) is associated with improved
patient and graft survival as compared with transplantation in previously
dialyzed patients. Complications related to dialysis are avoided in preemptively
transplanted patients. Psychological functioning of those patients is still under
investigation. The aim of the study was to evaluate the acceptance of illness,
satisfaction of life, and anxiety in patients preemptively transplanted (PET) and
transplanted after dialysis (PTD). METHODS: The present study compares 23 pairs
of PET and PTD patients after kidney transplantation from the same donor. Each
patient completed a set of psychological questionnaires: Acceptance of Illness
Scale, Satisfaction With Life Scale, and State-Trait Anxiety Inventory. Pairs
were examined in the same moment, from 7 days to 5 years after transplantation.
The PET and PTD groups did not differ significantly in respect to sex, underlying
renal diseases, incidence of acute rejection, surgical complications, and graft
function. More PTD patients had delayed graft function (P < .05). RESULTS: The
statistical analysis revealed a significant lower acceptance of illness as well
as satisfaction with life in PET recipients (P < .05). The groups differed
significantly in the trait of anxiety but not in the state of anxiety.
CONCLUSIONS: Although the medical benefits of PKT are widely known, numerous
psychological problems may occur in patients who do not have difficulties of
dialysis and who after transplantation are faced with unexpected discomfort,
which influences psychological well-being. Further effort should focus on
providing psychological support during qualification to the transplantation and
in follow-up after surgery.
PMID- 27496439
TI - Lowering of Messenger Ribonucleic Acid Toll-Like Receptors 2-4,9 in Peripheral
Blood Mononuclear Cells in Kidney Allograft Recipients, Relationships With
Immunosuppressive Treatment, and Delayed Graft Function Occurrence.
AB - BACKGROUND: Both tacrolimus (Tac) and cyclosporine (CsA) inhibit control
peripheral blood mononuclear cells (PBMC) after stimulation of various Toll-like
receptors (TLR) at supra-pharmacological concentrations. Earlier studies
demonstrated that 24 hours after kidney transplantation (KT), the expression of
the TLR4 messenger RNA (mRNA) in PBMC from patients with subsequent delayed graft
function (DGF+) was lower than in patients without DGF (DGF-). An assessment was
made of the interaction of immunosuppression with TLR mRNA in PBMC and to verify
whether the reduced expression of TLR-2,3,4,9 mRNA in PBMC is permanent in DGF+.
METHODS: We investigated mRNA expression of TLR in non-stimulated PBMC. All
patients were transplanted more than 1 month before PBMC acquisition. Patients
were divided into groups with respect to positive or negative history of delayed
graft function (DGF+/-). RESULTS: The expression of TLR2, TLR3, and TLR9 in
patients was lower than that in the control group. We found an association of Tac
C0 with expression of TLR4 only and CsA dose per 1 kg body weight with TLR2 or up
to 6 months after KT with TLR9. Mofetil mycophenolate (MMF)contributed to the
change of TLR4 expression in the CsA group but not in the Tac group. TLR3 and
TLR9 were nearly equally sensitive to both Tac and CsA, with a decrease of
expression with respect to control. DGF+ was associated with variable degree of
reduction of TLR2, TLR3, TLR4, and TLR 9 expression. CONCLUSIONS: We showed the
importance of immunosuppression and delayed graft function as factors that modify
the overall expression of mRNA-TLR PBMC for a period of time after KT. Patients
with a history of DGF have chronically decreased expression of mRNA TLR2, TLR3,
TLR4, and TLR9. This fact is associated with poorer graft function. Measuring the
expression of the TLR in the upper range of therapeutic doses of calcineurin
inhibitors and MMF gives the opportunity to assess the strength, effectiveness,
and toxicity of immunosuppression.
PMID- 27496440
TI - Impact of Skin Cancer Awareness on Prophylactic Behavior Among Renal Transplant
Recipients.
AB - BACKGROUND: Renal transplant recipients (RTRs) have a risk for skin cancer. The
most important risk factor, and the only one that depends on patient behavior, is
the exposure to ultraviolet light. The aim of this study was to assess the level
of skin cancer awareness and its impact on preventative behavior among RTRs.
METHODS: Questionnaires were applied to assess the awareness of increased risk of
skin cancer and its influence on preventative behavior among RTRs. RESULTS: Of
the RTRs, 51.6% considered themselves as a group of patients with a high risk of
skin cancer. Only 11.5% (group A) were able to fully explain the whole reason of
the need for sun protection usage. A partial explanation was provided by 40.1% of
the patients (group B). The other 48.5% of the patients (group C) provided no
explanation. Among the patients, 53.9% of surveyed RTRs never applied any
sunscreen. Of RTRs, 22.5% claimed to always avoid direct exposure to sunlight.
Most of the patients admitted to having outdoor hobbies (81% of group A, 60.3% of
group B, 58% of group C). In addition, 36.2% of RTRs thought that they were more
attractive if they were tanned. CONCLUSIONS: The awareness of being in a group of
increased risk of skin cancer is still poor among RTRs. Skin cancer awareness
does not correlate with usage of different forms of sun prevention. There is a
great need for active education of Polish RTRs.
PMID- 27496441
TI - Should We Be Concerned About Asymptomatic Adnexal Masses in Female Kidney and
Liver Graft Recipients?
AB - BACKGROUND: Pathological changes of uterine adnexa are frequently encountered in
patients after solid-organ transplantation. The aim of the study was to evaluate
the incidence of malignancies among recipients operated with the diagnosis of
adnexal tumor with or without clinical symptoms. METHODS: We retrospectively
analyzed data from 146 solid-organ recipients who underwent surgery in the First
Department of Obstetrics and Gynecology, Medical University of Warsaw, in the
years 2000 to 2014. Among them, we identified 80 patients of mean age 40.9 +/-
11.1 years with suspected adnexal tumor. Data on symptoms reported by patients
were compared with the results of histopathological examination after surgical
treatment. RESULTS: Kidney recipients were 76.2% of the group studied (including
5 women after kidney and pancreas transplantation); the remaining 23.75% of
patients were liver recipients (including 1 kidney and liver). The majority of
patients (71.25%) reported no clinical symptoms. The remaining 28.75% of patients
had clinical complaints, with the most common symptom being abdominal pain (in
60% of patients). Analysis of the results of histopathological examination
revealed that in both groups, the most often encountered pathological findings
were serous cystadenoma (33.3% and 47% of patients, respectively), endometrial
cysts (24.6% and 21.7%, respectively), and functional cysts (22.8% and 17.3%,
respectively). None of the asymptomatic patients were diagnosed as malignant,
whereas 2 cases (both ovarian and fallopian tube cancer) were diagnosed among
women who reported clinical symptoms. CONCLUSIONS: Observations of patients after
organ transplantation indicate a recurring nature of adnexal changes, resulting
in qualification for surgical treatment. The survey results suggest that solid
organ recipients with pathology in the uterine adnexa, with non-suspicious
ultrasound image and not reporting clinical symptoms, could safely be subjected
to clinical observation providing strict supervision.
PMID- 27496442
TI - Tissue Doppler Imaging and Intima-Media Thickness as Noninvasive Methods of
Cardiovascular Risk Stratification in Patients After Kidney Transplantation.
AB - BACKGROUND: Cardiovascular complications, including coronary artery disease and
chronic heart failure, are the leading causes of death in patients with chronic
kidney disease. New echocardiographic techniques, such as tissue Doppler imaging
(TDI) with strain and strain rate, are noninvasive, easy-to-perform methods of
the estimation of left ventricular (LV) systolic and diastolic function. The aim
of the study was to analyze the utility of new noninvasive methods of
cardiovascular risk stratification in patients after kidney transplantation.
METHODS: We included 43 consecutive kidney transplant (KT) recipients, with 30
healthy subjects constituting the control group in the study. We evaluated LV
morphology and LV systolic and diastolic function by means of echocardiography
with TDI and intima-media thickness by ultrasonography of the carotid arteries.
RESULTS: LV mass index was significantly higher in transplanted patients, and
both mitral inflow E/A and Em/Am ratios from pulsed myocardial imaging were
significantly lower in the KT group as compared with the control group. The
systolic wave of TDI at the basal segments was much lower in KT patients than in
the control patients (P < .05). The mean value of strain rate was reduced in KT
recipients as compared with the control patients. IMT was significantly higher in
KT recipients. CONCLUSIONS: Echocardiography with TDI provided more accurate
information about systolic and diastolic LV function. KT recipients showed
significant alterations in LV longitudinal myocardial function parameters
estimated by strain and strain rate. Strain and strain rate are noninvasive
methods, easy to repeat, and valuable for detecting myocardial LV dysfunction in
asymptomatic KT recipients.
PMID- 27496443
TI - Tacrolimus Metabolite M-III May Have Nephrotoxic and Myelotoxic Effects and
Increase the Incidence of Infections in Kidney Transplant Recipients.
AB - BACKGROUND: Tacrolimus (Tac) is one of the most commonly used immunosuppressive
drugs after solid organ transplantation. Eight Tac metabolites have been
described, but their clinical importance remains unclear. The aim of this study
was quantification of the 2 major Tac metabolites, 13-O-demethyl (M-I) and 15-O
demethyl (M-III), in kidney transplant recipients and to link them with
parameters of kidney and liver function, peripheral blood cell counts, and
infection incidence. METHODS: In 81 kidney transplant recipients, concentrations
of Tac, M-I, and M-III were measured with the use of liquid chromatography
combined with tandem mass spectrometry (LC-MS-MS). RESULTS: There was a negative
correlation between M-III levels and estimated glomerular filtration rate (eGFR;
r = -0.244; P < .05). Also, a negative correlation between M-III concentrations
and red blood cell count (RBC) was found (r = -0.349; P < .05). Neither
concentrations of Tac nor of M-I correlated with eGFR or RBC. M-I, M-III, and Tac
were not related to alanine aminotransferase activity. Significantly higher Tac
and M-III concentrations in the group with all types of infections in comparison
with the group without infections were observed (6.95 +/- 2.09 ng/mL vs 5.73 +/-
2.43 ng/mL [P = .03] and 0.27 +/- 0.17 ng/mL vs 0.20 +/- 0.11 ng/mL [P = .04],
respectively). CONCLUSIONS: The results suggest that higher concentrations of M
III may have a nephrotoxic or myelotoxic effect and result in higher incidence of
infections. Further studies are needed to confirm if monitoring of M-III could
minimalize adverse effects such as nephrotoxicity or infections.
PMID- 27496444
TI - Cardiovascular Risk Factors and Markers of Atherosclerosis in Stable Kidney
Transplant Recipients.
AB - BACKGROUND: There is limited evidence regarding the risk factors influencing
vascular injury in kidney transplant recipients, except for accelerated
vasculopathy and endothelial dysfunction in the pre-transplantation period of end
stage renal failure. Therefore, we performed a cross-sectional study to evaluate
the role of traditional and novel or potential nontraditional risk factors in
vascular and endothelial dysfunction in a cohort of stable kidney transplant
recipients. METHODS: One hundred forty-two kidney transplant recipients at 8.4 +/
1.8 years after transplantation were enrolled into the study. Different markers
of vascular injury, such as carotid intima-media thickness (IMT), pulse wave
velocity (PWV), and peripheral arterial tonometry (PAT), were assessed.
Inflammatory markers, oxidative stress and endothelial function surrogate
markers, adhesion molecules, and parathormone and osteoprotegerin levels were
measured. RESULTS: Among traditional risk factors, only age, pre-transplantation
diabetes, left ventricular hypertrophy (LVH) and cardiovascular disease (CVD)
were related to increased IMT and PWV, whereas PAT values were significantly
decreased only in diabetics and patients with CVD and were similar in patients
with and without LVH. In multivariate regression analysis, IMT was explained by
age, previous CVD episodes, and higher high-sensitivity C-reactive protein
levels, and PWV by age and pre-transplantation diabetes. The regression analysis
failed to find any significant explanatory variables for PAT. CONCLUSIONS: 1. In
stable kidney transplant recipients, age, pre-transplantation diabetes, previous
cardiovascular episode, and systemic microinflammation were predictors of
vascular injury. 2. PAT is poorly associated with traditional CV risk factors and
does not correspond with levels of biochemical markers of endothelial dysfunction
in those patients.
PMID- 27496445
TI - Hydroxylated, Hydroxymethylated, Dihydroxylated, and Trihydroxylated Cyclosporine
Metabolites Can Be Nephrotoxic in Kidney Transplant Recipients.
AB - BACKGROUND: Cyclosporine (CsA) is an immunosuppressive agent whose use is
associated with adverse effects, including nephrotoxicity. There are reports
indicating that some CsA metabolites may contribute to these effects. This study
was aimed at evaluation of CsA metabolites and correlating them with kidney
function. METHODS: In 62 kidney transplant recipients (41.9% women; overall mean
age, 48.44 +/- 11.75 years), concentrations of CsA and 4 groups of metabolites
were assessed: hydroxylated (HCsA), hydroxymethylated (HMCsA), dihydroxylated
(DHCsA), and trihydroxylated (THCsA). The results were normalized with the use of
the metabolite-to-parent drug ratio, and results were linked with estimated
glomerular filtration rate (eGFR) at 3 months before (-3M), point zero (0M), and
after 3 (+3M) and 12 (+12M) months. RESULTS: Multivariate analysis demonstrated
the negative influence of eGFR -3M on HMCsA/CsA (beta = -0.266; P < .05) and the
negative influence of HCsA/CsA, HMCsA/CsA, DHCsA/CsA, and THCsA/CsA on eGFR +3M
(beta = -0.339, beta = 0.396, beta = -0.314, and beta = -0.321, respectively; P <
.005) and eGFR +12M (beta = -0.363, beta = -0.316, beta = -0.267, and beta =
0.312, respectively; P < .05). We did not detect such influence of CsA
concentrations on eGFR +3M and +12M. The THCsA/CsA receiver operating
characteristic cutoff value for prediction of improvement of kidney function at
+12M was 0.143. CONCLUSIONS: Our results suggest that impaired function of the
transplanted kidney affects the accumulation of HMCsA. It is possible that the
increased metabolite (HCsA, HMCsA, DHCsA, and THCsA) to cyclosporine ratio could
influence or could be a marker of cyclosporine nephrotoxicity. In this context,
the most promising marker seems to be THCsA/CsA ratio, but its real significance
requires further studies to determine.
PMID- 27496446
TI - Congenital Infections in Neonates of Women With Liver or Kidney Transplants.
AB - BACKGROUND: Immunosuppressive therapy is associated with an increased risk of
pregnancy complications and may have adverse effects for the newborn. The aim of
this study was to determine the frequency and the type of early congenital
infections and to assess typical markers of infections in neonates of liver and
kidney recipients. METHODS: A retrospective analysis of 71 neonates born to
either liver (39 cases) or kidney transplanted women (32 cases) was conducted.
The rate and the type of newborns' infections as well as laboratory and
bacteriologic markers of infections were analyzed. RESULTS: There was no
significant difference in the frequency of congenital infections between the LT
and KT groups (8 vs 7 cases; P = .879).). The rate of infections was not
significantly higher in both groups compared with the general population.
Infections were detected in 23.9%, 13.6%, and 26.6% of neonates born to mothers
using tacrolimus, cyclosporine, and azathioprine respectively. No significant
differences in white blood count or levels of neutrocytes and lymphocytes were
observed between the groups. No abnormalities in white blood smear, but 1 case of
leukopenia in the kidney transplant group, were detected. CONCLUSIONS: The rate
of congenital infections in neonates of allograft recipients is not significantly
higher than in the general population. Immunosuppressive regimens with
azathioprine seem to carry the greatest risk, it is a little lower in the
tacrolimus group, and cyclosporine-based regimens have the lowest risk of
congenital infections. Differences were not statistically significant. Prenatal
exposure to immunosuppressive agents seems not to be associated with any
hematologic disturbances in white blood count and white blood smear.
PMID- 27496447
TI - Association of MYH9 rs3752462 and rs5756168 Polymorphisms With Transplanted
Kidney Artery Stenosis.
AB - Allelic variants of the MYH9 gene, encoding myosin nonmuscle heavy chain type
IIA, have been shown to correlate with diminished glomerular filtration rates and
end-stage kidney disease in individuals of Caucasian ancestry. Myosin nonmuscle
heavy chain type IIA is expressed during development as well as in injured
vessels and kidney structures. We hypothesized that MYH9 risk variants may
correlate with kidney artery injury and dysfunctional healing, such as transplant
renal artery stenosis (TRAS). Our study aimed at evaluating the association of
MYH9 risk allelic variants (rs4821480, rs4821481, rs3752462, rs11089788,
rs136211, rs5756168, rs2032487, and rs2239784) with TRAS, defined as >50% renal
artery lumen reduction. Genotyping was performed with the use of custom Taqman
genotyping assays on DNA samples (n = 295) from white deceased-donor kidney
transplant recipients and genomic DNA from the corresponding donors. Statistical
analysis was performed with the use of Kaplan-Meier estimates, log-rank tests,
and proportional hazard Cox models. Recipients carrying TT in rs5756168
experienced diminished risk of TRAS (hazard ratio [HR], 0.31; P < .009), whereas
organs carrying CC in rs3752462 were exposed to excessive TRAS risk (HR, 2.54; P
< .047). In multivariate stepwise analysis TRAS was 10.9-fold increased in
kidneys originating from rs3752462 CC, whereas the risk was decreased 3.45-fold
(adjusted HR, 0.29) in recipients carrying rs5756168 TT (P < .007 and P < .033,
respectively). Intracranial bleeding or trauma compared with other mechanisms of
donor death diminished TRAS risk by 87% and 91%, respectively (P < .030 and P <
.017). Our study is the first to identify genetic predisposition to transplant
renal artery stenosis.
PMID- 27496448
TI - Gastrointestinal Pathologies in Patients After Successful Renal Transplantation-A
Pilot Study.
AB - BACKGROUND: The beneficial effect of kidney transplantation in patients requiring
continuous renal replacement therapy owing to chronic kidney disease is well
known and accepted. Kidney transplantation protects the patient from
complications that may develop during chronic dialysis. Unfortunately, there is
also evidence that kidney transplant patients are more prone to developing cancer
than healthy persons. The aim of this study was to evaluate the prevalence of
gastrointestinal pathologies in patients after kidney transplantation. METHODS:
Adult patients after kidney transplantation, who are under the care of the
Outpatient Department of Nephrology in Gdansk, received alarm symptom
questionnaires and referral for testing for the presence of fecal occult blood.
Then, in 45 selected patients (29 men and 16 women) endoscopic examination was
performed. Mean age was 57.6 +/- 10.1 (range, 35-83) years. RESULTS: Out of ~940
patients after kidney transplantation, resting under supervision of outpatient
department, 181 patients completed the questionnaire and 100 gave a stool sample
for testing: 32 results were positive. After analyzing the questionnaires and
stool results, 88 patients were qualified for further investigation. The
endoscopic examination had been performed so far in 45 patients and revealed
gastritis and/or duodenitis in 33 patients, diverticular colon disease in 18,
esophagitis in 8, colon polyps in 14, stomach polyps in 3, inflammatory bowel
disease in 7, and cancers in 3. CONCLUSIONS: The preliminary results indicate
that patients after kidney transplantation have significant risk of
gastrointestinal pathologies and require detailed diagnostic endoscopy.
PMID- 27496449
TI - Cardiovascular Risk Evaluated With the Use of Heartscore in Kidney Transplant
Recipients-Three Years of Follow-up.
AB - BACKGROUND: Cardiovascular (CV) complications are the major cause of death in
kidney transplant (KT) patients. METHODS: During a 3-year follow-up, 112 KT
recipients, from living (LD KTRs; n = 54), and deceased (DD KTRs; n = 58) donors,
were assessed for 10-year risk of fatal CV events with the use of the Heartscore
tool (www.heartscore.org). In post-KT months 6, 12, and 36, current and optimum
(target) CV risks (CVRs) were estimated. RESULTS: Current risk was lower in the
LD KTRs and remained stable. In DD KTRs, the risk was at the highest level in
months 6 and 12 of follow-up and decreased in month 36. Change in CVR, ie, the
difference between the current and target risk, was the highest in DD KTRs in
month 36 of follow-up (P = .014). In the increased-CVR group, recipients were
older (P < .01), primarily male (P = .08), and more frequently smokers (P < .01)
and had a higher systolic blood pressure (P < .05) despite taking more
hypotensive medicines (P < .01), and had higher total cholesterol (P < .01) and
low-density lipoprotein (P < .01) levels. In this group, body mass index (BMI)
was higher (P < .01) and metabolic syndrome was diagnosed significantly more
often (P < .01). The high-risk group (estimated CVR, >=5) was different also in
longer durations of pre-transplantation dialysis (P < .05) and higher rates of CV
episodes before transplantation (P < .05). In logistic regression, higher BMI and
lower estimated glomerular filtration rate (eGFR) were the parameters strongly
correlated with higher CVR. CONCLUSIONS: Mean CVR applicable to all kidney
transplant recipients was stable throughout the follow-up. Changes in the risk
affected mainly DD KTRs. In months 6 and 12, CVR was the highest in this group
and was substantially reduced in the 3rd year of follow-up, probably owing to
medical interventions. In the high-CVR group, impaired function of the
transplanted kidney was recorded. CVR scores in patients with renal conditions
and after kidney transplantation should additionally account for eGFR.
PMID- 27496450
TI - Successful Treatment of Urinary Tract Infection in Kidney Transplant Recipients
Caused by Multiresistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta
Lactamase (NDM-1) With Strains Genotyping.
AB - BACKGROUND: Klebsiella pneumoniae New Delhi metallo-beta-lactamase-1 (NDM-1)
strains have recently become a new threat in kidney transplant recipients due to
the strains' resistance to almost all antibiotics, including carbapenems.
METHODS: We present a case series of 3 patients with urinary tract infections
(UTIs) caused by multiresistant K pneumoniae NDM-1 strains who were treated with
the same protocol. Genotyping sequencing with pulsed-field gel electrophoresis
was performed in all cases. RESULTS: All patients were male and had undergone
kidney transplantation 4, 7, and 8 months, respectively, before the admission.
Combined antibiotic therapy consisting of imipenem/cilastatin in maximal doses,
gentamicin and/or colistin for 21 to 27 days, followed by oral fosfomycin, was
used in all cases. There were no further UTI episodes in 2 patients at the 12
month visit. Three months after initial treatment, the third patient presented
with leukocyturia with no clinical symptoms and a urine culture positive for K
pneumonia NDM-1 strain. Interestingly, the strain was susceptible to
trimethoprim/sulfamethoxazole despite resistance in previous urine culture
samples. The patient was successfully treated with trimethoprim/sulfamethoxazole
2 * 960 mg/d for 3 weeks followed by 480 mg/d and 3 doses of fosfomycin.
Genotyping sequencing revealed identical DNA restriction fragments in bacterial
strains from 2 patients. In the third case, although a difference in 2
restriction fragments was observed, the strain was considered related to the
others. CONCLUSIONS: In cases of UTI caused by K pneumoniae NDM-1 strains,
prolong combined treatment followed by oral fosfomycin prophylaxis can be
successful. Strain genotyping should be performed to optimize further treatment
protocols in such cases.
PMID- 27496451
TI - Urinary Tract Infections in Kidney Transplant Recipients Hospitalized at a
Transplantation and Nephrology Ward: 1-Year Follow-up.
AB - INTRODUCTION: The aim of this study was to investigate risk factors for urinary
tract infections (UTI), the causative organisms of UTI and also their management
and treatment. In addition, we evaluated the effects of UTI on renal graft
function. METHODS: This analysis included 107 kidney transplant recipients (64%
women) with a diagnosis of UTIs confirmed by positive results on urine culture.
Type of pathogens, sensitivity to drugs, risk factors for infection, incidence of
urosepsis, hospitalization period, treatment methods, and recurrence rates were
analyzed. Statistical analysis was performed by using Pearson's chi(2) test,
Yates' chi(2) test, the Student t test, Welch's t test, the Mann-Whitney U test,
Fisher's exact test, and the Shapiro-Wilk normality test. RESULTS: The most
common species isolated from urine samples included Escherichia coli (42%),
Klebsiella pneumoniae (15%), and Enterococcus faecalis (10%). The percentage of
multidrug-resistant strains was 31%, and urosepsis was diagnosed in 16% of
patients. Recurrences developed in 76% of infected patients. Bricker
ureterointestinal anastomosis was performed in 11% of patients. Risk factors for
severe infections included: pre-transplantation urinary tract surgery (P = .02),
double-J stent insertion (more common in men) during KTx (N = 34; 32%), (P =
.021), reoperations following transplantation (P = .36), elevated tacrolimus
levels at the time of infection (P = .024). Severe infections were diagnosed in
patients with lower eGFRs, were associated with a need for longer hospitalization
(P = .04) and escalation of antibacterial treatment. Carbapenems were used in 22
patients (20.5%). CONCLUSIONS: UTIs were more common in women, in patients with
impaired function of the kidney transplant, and in those with a history of
urinary tract interventions. Severe infections were associated with a risk of
urosepsis, longer hospitalization, and a need for escalation of antibiotic
treatment.
PMID- 27496452
TI - Comparison of Staphylococcal Flora in Denture Plaque and the Surface of the
Pharyngeal Mucous Membrane in Kidney Transplant Recipients.
AB - BACKGROUND: Biofilm occurring on removable prostheses is a reservoir of bacterial
flora, consisting of both physiological and pathogenic multidrug-resistant
microorganisms. Patients undergoing dialysis and organ transplantation are
particularly prone to bacterial infections, which can have its source in denture
plaque. This study was a comparison of the composition of staphylococcal flora
within the surface of the pharyngeal mucous membrane as well as denture plaque in
kidney transplant recipients. METHODS: The study included 44 subjects with
removable prostheses who reported for a kidney transplant procedure. Swab samples
were collected from prostheses and the pharyngeal wall. Isolated strains were
identified and investigated for drug resistance. RESULTS: A total of 72 strains
of Staphylococcus were isolated from the denture plaque and 53 from the pharynx.
In the pharynx, the following species prevailed: Staphylococcus epidermidis,
Staphylococcus warneri, and Staphylococcus aureus. The following species
prevailed in denture plaque: S epidermidis, S aureus, and Staphylococcus
haemolyticus. Among the pharyngeal strains, antibiotic resistance most commonly
referred to natural penicillin (77%), constitutive macrolide-lincosamide
streptogramin B resistance (28%), and tetracycline (26.4%). In case of denture
plaque, the highest percentage of strains demonstrated resistance to natural
penicillin (60%), fosfomycin (32%), and cefoxitin (25%). In 10 subjects (48%),
Staphylococcus-induced infections occurred in the first year after
transplantation, 5 of which had the same bacterial strain as cultured previously
from dentures. CONCLUSIONS: The denture biofilm and surface of the pharynx differ
in terms of bacterial composition and bacterial drug resistance profiles. Denture
plaque constitutes a considerable reservoir of staphylococcal flora, which can be
a potential source of infection in organ transplant recipients.
PMID- 27496453
TI - Cooperation in Treatment as an Indicator of Adaptation of Kidney Transplant
Patients to Chronic Therapy.
AB - BACKGROUND: Cooperation between patients and physicians in chronic treatment is
an important factor in the patients' adaptation to difficult circumstances. The
search is ongoing for factors important to the physician-patient relationship,
with the goal of identifying deficits and psychological resources of the patients
and medical soft skills of the physicians that can affect the quality of
cooperation. The aim of this study was to analyze the psychological mechanisms of
patient cooperation with physicians in the area of treatment after kidney
transplantation. METHODS: The study group consisted of 105 patients (62 male
patients and 43 female patients) aged 25 to 82 years (mean age, 50.91 years)
after kidney transplantation who remained in the follow-up protocol of the
Outpatient Transplant Clinic. A questionnaire was used to examine the
compatibility of ratings as expressed by the patients and their physicians in 10
areas of cooperation in treatment. The tests for a sense of self-efficacy
(General Self-Efficacy Scale), optimism (Life Orientation Test-Revised), and the
control of emotions (Courtauld Emotional Control Scale) in Juczynski's adaptation
were used in the study of psychological factors. RESULTS: Only 1 case reached
total congruity by the patients and their physicians in all 10 areas of
cooperation. In 3 areas, compliance was achieved in 70%, 72%, and 76%,
respectively; in 6 areas, 50% to 66%; and in 1 sphere, 37%. We found no
significant impact of psychological factors on patient compliance. A comparison
was made of 2 groups of patients (1 of which was characterized by a high
compatibility between the physician and patient assessments, and the second which
was characterized by the lack of conformity). Moreover, assessment of the
functioning of the transplanted kidneys was rated higher in those patients who
achieved a high compliance with the opinions of medical cooperation in the
treatment. CONCLUSIONS: The quality of cooperation measured by using compliance
assessments of the patients and physicians in health behaviors is satisfactory.
This finding translated into a favorable assessment of the functioning of the
transplanted kidney expressed by the patients. Qualitative information provides
guidance for targeted increasing collaboration.
PMID- 27496454
TI - Prognostic Value of Proinflammatory Markers in Patients After Kidney
Transplantation in Relation to the Presence of Diabetes.
AB - BACKGROUND: Patients who are receiving immunosuppressive treatment after kidney
transplantation are at greater risk of developing new-onset diabetes after
transplantation (NODAT). New biochemical markers that may contribute to a better
assessment of the prognosis of renal failure for patients diagnosed with diabetes
mellitus (DM) are needed. The aim of this study was to assess selected
proinflammatory markers in patients after kidney transplantation depending on the
prevalence of DM and to evaluate the predictive value of these cytokines.
METHODS: A total of 82 patients were divided into 3 groups after kidney
transplantation and were included in the analysis: group I, no DM; group II, DM
diagnosed before transplantation; and group III, NODAT. Selected marker levels
(platelet-derived growth factor, transforming growth factor beta1, tumor necrosis
factor receptor II [TNF-RII], and high-sensitivity interleukin-6 [IL-6 HS]) were
assessed by using enzyme-linked immunosorbent assays. For summary endpoint, a
return to dialysis treatment and/or death of the patient was adopted. RESULTS:
Patients with NODAT were characterized by higher levels of IL-6 HS and body mass
index. There were no statistically significant differences in the levels of other
assessed markers among the 3 analyzed groups. The summary endpoint was observed
in 16 cases (19.5%). Patients with summary endpoint during the observation time
at baseline had higher levels of TNF-RII (7180 vs 4632 pg/mL; P = .0002) and IL-6
HS (4.58 vs 2.72 pg/mL; P = .033). CONCLUSIONS: Levels of inflammatory markers in
patients after kidney transplantation did not differ between groups with and
without DM. In the study population, DM was not a significant risk factor for
graft loss or death. Patients who experienced these complications at baseline
were characterized by higher values of TNF-RII and IL-6 HS.
PMID- 27496455
TI - Association Between HLA Type and Skin Cancer in Kidney Transplant Recipients.
AB - BACKGROUND: Organ transplant recipients (OTRs) are more susceptible to various
diseases, among them cancers. Nonmelanoma skin cancers (NMSC) represent the most
common malignancies in OTRs in Europe. Due to the significantly higher morbidity,
aggressive and rapid progression, and poor prognosis of NMSC in the OTR
population, these patients require a special oncological approach. Intensive
attention should therefore be paid to factors predisposing OTRs to the
development of cancer. The aim of this study was to establish the role of genetic
factors in the pathogenesis of skin cancer in kidney transplant recipients
(KTRs). METHODS: This single-center study was performed in 39 KTRs with
posttransplant NMSC. The frequency of particular types of HLA Class I (HLA-A and
HLA-B) and Class II (HLA-DR) in each group were compared to establish the
association between the HLA type and risk of skin cancer after renal
transplantation. RESULTS: HLA-DR15 were more commonly detected in patients with
MNSC than in the control group of KTRs (P = .014) There was also a positive
correlation between HLA-B18 and skin squamous cell carcinoma. The antigen was
more often recorded in KTRs with squamous cell carcinoma than in KTRs without
NMSC (P = .03) and in the general population (P = .002). CONCLUSIONS: Patients
who are positive for HLA-BR15 and HLA-B18 should be under special dermatologic
surveillance due to the potentially high risk of skin cancer.
PMID- 27496456
TI - Nephropathy Evolving Within the First Two Posttransplant Months With No Typical
Cytopathic Lesions: Two Cases Presentation.
AB - BACKGROUND: We report 2 cases of polyomavirus-associated nephropathy (PyVAN)
emerging within the initial 8 posttransplant weeks. These cases were
characterized by intraepithelial BK virus replication without typical nuclear
inclusions in epithelial cells. METHODS AND RESULTS: A 70-year-old male recipient
of a cadaveric kidney transplant had experienced unsatisfying graft function
since the time of transplantation (Tx). One month after Tx, results of a graft
biopsy revealed mild tubulointerstitial inflammation. No intraepithelial nuclear
inclusions suggestive of viral infection were present at that time. The patient
received intravenous methylprednisolone, and the dosage of tacrolimus was
increased. Due to a further drop in the glomerular filtration rate, a subsequent
kidney biopsy was performed during posttransplant week 10, which revealed lesions
typical of PyVAN. Retrospectively performed SV40 staining revealed that
intragraft polyomavirus replication was already present on posttransplant day 30.
Basic immunosuppression reduction and ciprofloxacin administration were followed
by BK viremia elimination, stabilization of graft function, and resolution of
PyVAN. In another patient, a 62-year-old male recipient of a cadaveric renal
graft, BK viremia was monitored from the time of Tx. Two months after Tx, the
patient was found to have a BK viral load of 6 * 4 log(10)/mL. Results of the
graft biopsy revealed fully preserved tubular epithelium, but SV40 staining was
positive in some of these cells. After basic immunosuppression reduction and
introduction of ciprofloxacin, the BK viral load dropped to 1 * log(10)/mL with
graft function stabilization. CONCLUSIONS: PyVAN may emerge as early as 4 weeks
after Tx, with near-normal or acute rejection-like graft morphology. The early
monitoring of plasma BK viral load, as well as SV40 staining, avoids misdiagnosis
of this severe posttransplant complication.
PMID- 27496457
TI - Effects of Immunosuppressive Drugs on Serum Fatty Acids of Phospholipids Fraction
in Renal Transplant Recipients.
AB - BACKGROUND: Immunosuppressive medications often cause posttransplant
hyperlipidemia. The effects of cyclosporine (CsA) and tacrolimus (Tac) on lipid
profile is well-known; however, there are very few studies related to the effect
of these immunosuppressants on fatty acids (FA) of phosholipids fraction (PL) in
renal transplant recipients (RTR). We sought to analyze the FA profile in PL
fraction of RTR treated with Tac or CsA. METHODS: The study included 65 renal
transplant patients on CsA (n = 24, group I) or Tac (n = 41, group II), and 14
healthy controls. Individual serum FA concentrations were measured by gas
chromatography. Chemstation software was used to analyze the data. RESULTS: No
differences between studied groups and controls were noted for monounsaturated
FA, polyunsaturated n-3 FA (PUFA n-3), PUFA n-6, or the ratio of PUFA n-6 to PUFA
n-3. The following mean values of FA were significantly higher in the CsA-RTR and
Tac-RTR as compared with controls: total FA (P < .01 in both cases), saturated FA
(SFA; P < .02 in both cases), C12 (P < .003 in both cases), C18 (P < .003 in both
cases), and C18:2 (P < .01 for CsA RTR; P < .02 for Tac RTR). No differences
between the measurements in patients on CsA and in patients on Tac were noticed.
Significant correlation between SFA and eGFR was observed only in the CsA RTR
group (P < .05). A negative relationship between PUFA n-6 and the estimated
glomerular filtration rate was seen, but the correlation was not significant.
CONCLUSIONS: Immunosuppressive drugs may affect FA metabolism, but the FA profile
does not depend on the type of immunosuppressive drug administered.
PMID- 27496458
TI - Treatment of Persistent Hypercalcemia and Hyperparathyroidism With Cinacalcet
After Successful Kidney Transplantation.
AB - INTRODUCTION: Hypercalcemia caused by persistent hyperparathyroidism after
successful kidney transplantation (KT) is a common problem and may negatively
affect graft function, bone metabolism and the cardiovascular system. Cinacalcet
is a novel, available tool to control hypercalcemia after KT. The aim of the
study was to examine the efficacy of cinacalcet in lowering calcium in KT
recipients with persistent hypercalcemia owing to hyperparathyroidism. METHODS:
In this retrospective observational study, we analyzed 30 patients with
persistent hypercalcemia >10.8 mg/dL. All patients in the study were started on
cinacalcet at different points after KT, with the mean time of 43 +/- 37 months.
The initial dose of 30 mg/d was adapted progressively based on serum calcium
levels. RESULTS: During the observation period, graft function in all patients
was stable (estimated glomerular filtration rate [Chronic Kidney Disease
Epidemiology Collaboration formula] 64 +/- 25 mL/min/1.73 m(2)). The mean
baseline calcemia was 11.9 +/- 0.7 mg/dL, the intact parathyroid hormone value
was 490 +/- 228 pg/mL and phosphorus concentration was 2.2 +/- 0.5 mg/dL.
Treatment with cinacalcet resulted in a significant decrease in serum calcium
level (mean, 9.9 +/- 0.7 mg/dL; P < .001), a reduction in intact parathyroid
hormone level (308 +/- 199 pg/dL; P < .001), and an increase in phosphorus
concentration (mean, 2.8 +/- 0.6 mg/dL; P < .001). In 5 females, gastrointestinal
side effects were observed, requiring withdrawal of cinacalcet in 1 case.
CONCLUSIONS: Cinacalcet administered after KT seems to be an effective option for
the management of persistent hypercalcemia owing to hyperparathyroidism with
satisfactory tolerability and may be considered as a therapeutic alternative to
surgical parathyroidectomy or as a bridging therapy to parathyroidectomy.
PMID- 27496459
TI - Effect of Immunosuppressive Treatment on Carotid Atherosclerosis in Renal
Transplant Recipients.
AB - BACKGROUND: The aim of this study was to compare the effect of immunosuppressive
regimens using either mammalian target of rapamycin inhibitors (mTORi) or
calcineurin inhibitors (CNI) on the risk of atherosclerosis in renal transplant
patients. MATERIALS AND METHODS: The study involved a group of 24 recipients
treated with mTORi (mTORi group) and a group of 20 recipients treated with
immunosuppressive regimen based on CNI (CNI group). Laboratory and clinical
markers of cardiovascular risk in both groups were investigated. Carotid
atherosclerosis was evaluated by measurement of the intima media thickness (IMT)
of the common and internal carotid artery walls and detection of carotid plaques
by a high-resolution ultrasonography. The study was performed 3-24 years after
transplantation. RESULTS: The mTORi group showed higher level of total
cholesterol (242 vs 201 mg/dL; P < .004), low-density lipoprotein cholesterol
(140 vs 116 mg/dL; P < .05), and triglycerides (226 vs 168 mg/dL; P < .01).
Posttransplant diabetes developed in 34% of mTORi group compared with 25% in the
CNI group. The mean of IMT (left and right) of common and internal carotid
arteries was similar in both groups. Carotid plaques were detected in 46% of
patients from the mTORi group and 25% from CNI group (P < .02). The presence of
carotid plaques combined with an IMT of >0.9 mm were associated with male gender,
mTORi treatment (P = .03), and cardiovascular events. The incidence of coronary
heart disease was higher in mTORi group than in CNI group (53% vs 20%; P = .03).
CONCLUSIONS: There was not beneficial effect of immunosuppressive treatment with
mTORi on carotid atherosclerosis in renal transplant patients.
PMID- 27496460
TI - Influence of Double-J Catheters on Urinary Infections After Kidney
Transplantation.
AB - BACKGROUND: One of the most important problem in kidney transplantation is risk
of the urinary anastomosis stricture. In uncertain cases the use of a double-J
(or JJ) catheter is a standard solution. In case of urinary leak or fistula after
the reanastomosis operation, transuretheral JJ implantation is used. A number of
patients after JJ use present urinary infection. METHODS: Between 2012 and 2014,
283 kidney transplantations were performed in our center. In 77 cases (27.2%), a
JJ was used at the time of operation, in 10 other cases (3.5%) during
postoperative period. RESULTS: Urinary infection was observed in 95 patients
(33.6%), with Proteus, Klebsiella, Enterobacter, Escherichia, Enterococcus,
Pseudomonas, Morganella, and Staphylococcus cultures. In the group of patients
without JJ catheters, infections were found in 27.6% of cases and in group with
JJ, in 47.1% (46.8% in intraoperative use of catheters and 50% in postoperative
curse). CONCLUSIONS: The analysis shows that use of JJ catheters gives urinary
infections almost twice more frequent (47.1% vs 27.6%; P = .001) with no
difference if the implantation took place during or after the operation.
PMID- 27496461
TI - Does the Parathyroidectomy Endanger the Transplanted Kidney?
AB - BACKGROUND: Some investigators maintain that a parathyroidectomy (PTX) performed
for tertiary hyperparathyroidism may potentially cause graft malfunction or even
loss of the transplanted kidney after the operation. The goal of this study was
to determine if parathyroidectomy affects transplanted kidney function. METHODS:
The study group consisted of 48 renal graft recipients who underwent operation
due to tertiary hyperparathyroidism. Thirty-nine subtotal parathyroidectomies and
9 more selective, less than subtotal parathyroidectomies were performed. The
estimated glomerular filtration rate (eGFR) was calculated retrospectively on
days 2 to 3 and 4 to 5 and at 1, 3, 6, 12, 24, and 36 months after PTX; these
findings were compared with preoperative values. The cumulative graft survival
rate in the postoperative period was assessed. RESULTS: In the follow-up period,
4 of 48 patients returned to hemodialysis (after 1, 7, 22, and 57 months after
PTX). In the first case, the patient had stopped taking the immunosuppressive
drugs 1 month after PTX. Cumulative graft survival rate after PTX was 98.0% after
6 months, 96% after 12 months, and 93% after 2 and 3 years. The mean preoperative
eGFR was 52 +/- 17.15 mL/min/1.73 m(2), and the median was 48.28 mL/min/1.73
m(2). Overall and in the subtotal parathyroidectomy group, eGFR was significantly
lower (P < .001) only on days 2 to 3. There were no differences between
preoperative and postoperative eGFR values in the other follow-up periods. In the
more selective, less than subtotal parathyroidectomy group, the decrease in eGFR
values was nonsignificant compared with preoperative findings in the early
postoperative period as well as in all follow-up periods. CONCLUSIONS: In this
study, PTX did not significantly impair transplanted kidney function, but in the
early postoperative period, transient reductions in graft function did occur.
PMID- 27496463
TI - Prevalence of Left Ventricular Hypertrophy and Left Ventricular Dysfunction in
Older Renal Transplant Recipients.
AB - OBJECTIVE: Left ventricular hypertrophy (LVH) is a risk factor for premature
cardiovascular morbidity and mortality in chronic kidney disease. The aim of the
study was to determine echocardiographic evaluation morphology and function of
the left ventricle in older renal transplantation patients. MATERIAL AND METHODS:
We retrospectively analyzed clinical data of renal transplant recipients who
underwent routine echocardiography. We compared the data from 38 patients who
were older than 65 years with 49 patients who were a mean age of 47.8 +/- 12
years (control group). RESULTS: At the time of cardiac evaluation, most patients
were in stage 3 chronic kidney disease. In the older group of patients, the
incidence of obesity and diabetes were significantly higher than in the control
group. Also in the older patients, the serum level of albumin was lower (P <
.001), and brain natriuretic peptide was higher (P = .046). The incidence of
coronary heart disease, chronic heart failure, and atrial fibrillation were
higher in the older patients (P = .011). LVH was common in older as well as
younger patients (97.4% vs. 88.8%, P = .17). Left ventricle mass index ranged
from 90.4 g/m(2) to 235.5 g/m(2) among examined kidney transplantation patients.
In older patients, left ventricular mass index was 160.7 +/- 34.5 g/m(2) compared
to 141.8 +/- 29.8 g/m(2) in younger patients (P = .008). Reduced ejection
fraction was found only in 2 of 38 (5.3%) older patients. Diastolic dysfunction
of left ventricle was present in 34 of 38 (89.5%) patients >65 years old and in
24 of 49 (49.9%) younger patients (P < .001). CONCLUSIONS: LVH and left
ventricular dysfunction are more pronounced among older patients. Impaired renal
function, proteinuria, diabetes, and severity of hypertension are the most
important factors predisposing to LVH.
PMID- 27496462
TI - Treatment of the Lymphocele After Kidney Transplantation: A Single-center
Experience.
AB - BACKGROUND: Lymphocele is one of the most common complications after kidney
transplantation. It is usually asymptomatic, but can cause pressure on the kidney
transplant, ureter, bladder, and adjacent vessels with deterioration of graft
function, ipsilateral leg edema, and external iliac vein thrombosis. Peritoneal
fenestration is a well-established method for treatment. In this report, we
present the incidence of symptomatic lymphocele requiring treatment (LRT),
demographic and surgical factors that influenced lymphocele formation, its
clinical presentation, and 2 types of treatment: open and laparoscopic
intraperitoneal drainage in the experience of our center. MATERIAL AND METHODS:
We retrospectively analyzed all kidney transplantations performed between January
2007 and December 2014 in Gdansk Transplantation Center (n = 740) and selected
patients with LRT. LRT occurred in 59 cases (8%). All other patients transplanted
during the same time (n = 681) were treated as a control group in the univariate
and multivariate analysis of risk factors of the lymphocele formation. RESULTS:
Surgical intraperitoneal drainage was performed in an open method in 53 cases and
laparoscopically in 6 patients. We observed recurrence of lymphocele in 11 cases
(18.6%). Acute rejection episodes (ARE) and delayed graft function (DGF) were
more frequent in patients with LRT. ARE and age were independent risk factors for
LRT in multivariate analysis. The mean estimated glomerular filtration rate by
the Modification of Diet in Renal Disease method at 1 month after the
fenestration was higher than before the operation (51.7 and 43.6 mL/min,
respectively). CONCLUSIONS: Fenestration is a safe and effective method of
treatment of symptomatic lymphocele. ARE, DGF, and older age were associated with
a greater risk of LRT.
PMID- 27496464
TI - Psychological Predictors of Cooperation in the Chronic Treatment of Kidney
Transplantation Patients.
AB - INTRODUCTION: A patient who complies with doctor recommendations is an indicator
of proper cooperation in treatment. It is affected by environmental factors, soft
competences of the doctors, and properties of the human personality. We
investigated the psychological characteristics of patients that may facilitate
human contact and promote healthy behaviors. The aim of the study was to analyze
the importance of psychological factors for the occurrence of health-related
behaviors necessary for cooperation in treatment. MATERIAL AND METHODS: The study
was conducted in a group of 105 patients (62 males and 43 females) aged from 25
years to 82 years old (mean, 50.4 years) after kidney transplantation who
remained in follow-up at the Outpatient Transplant Clinic. We used two
questionnaires: one for the patients and one for their doctors, including an
assessment of healthy behaviors listed in 10 categories. The patients also
completed the tests exploring the sense of self-efficacy (generalized self
efficacy scale), optimism (life orientation test - revised) and the control of
emotions (Courtauld emotional control scale) in a Polish adaptation by Zygfryd
Juczynski. In the statistical analysis, the Spearman rank correlation coefficient
and the Kanonicza analysis were used, adopting the significance level of P < .05.
RESULTS: We found significant correlations between psychological factors and
behaviors of the patients. The patients controlling the expression of anxiety
often concentrated on cleanliness and hygiene (P = .013). The patients
controlling the expression of anger (P = .008) and anxiety (P = .049) were less
likely to perform self-observation, being of the opinion that the role of the
physicians was to evaluate the development of the disease and advances in
treatment. The patients with higher levels of optimism were perceived by the
physicians as better cooperating in conducting self-observation (P = .024) and
adherence to hygiene (P = .047); they were also less frequently struggling with
ophthalmic problems (P = .004). The relationship between the factors associated
with the disease and treatment (pressure, the efficiency of the transplanted
kidney, and duration of treatment) and psychological factors (optimism, emotional
control, and self-efficacy) has been confirmed. The emerged factors significantly
affected each other, which indicated the matching of the model (P = .08).
CONCLUSIONS: The analysis of the results shows that psychological and somatic
functioning of patients has a strong relationship with certain pro-health
behaviors that determine the collaboration in treatment. This can serve as a
basis for modifying the rules of managing the patients.
PMID- 27496465
TI - Clinical Utility of QuantiFERON-Cytomegalovirus Test in Management of Kidney
Transplant Recipients.
AB - Immune monitoring of cytomegalovirus (CMV) - specific T-cells responses has
become an additional tool in the CMV risk assessment of kidney transplant
recipients (KTRs). Some data demonstrated a potential use of QuantiFERON-CMV
assay (QF-CMV) in stratifying CMV risk before transplantation, at the end of
prophylaxis and during pre-emptive strategy. High risk for CMV disease was also
reported in KTRs with indeterminate QF-CMV results in which both mitogen and CMV
antigen responses were absent. Twenty-five KTRs in the first year after kidney
transplantation (KT), including 17 KTRs after CMV infection treatment (CMV-KTR),
were studied by QF-CMV assay. Positive QF assay (QF+) was present in 16 of 25
(64%) of KTRs, negative (QF-) in 5 of 25 (20%), and indeterminate (QF0) in 4 of
25 (16%). The QF0 patients, in comparison to the combined group of QF+ and QF-,
presented an increased incidence of CMV disease (4 of 4 [100%] vs. 7 of 21
[33.3%]; P < .05) and severe infectious complications such as sepsis, and
systemic mycosis (4 of 4 [100%] vs. 6 of 21 [29%]; P < .02). Of 17 CMV-KTRs, 11
of 17 (64.7%) were QF+, 2 of 17 (11.8%) were QF-, and 4 of 17 (23.5%) were QF0.
The incidence of CMV disease and severe infectious complications was not
different among these groups. CMV-KTRs with interferon-gamma <3.5 IU/mL vs. >3.5
IU/mL in mitogen tube, irrespective of QF-CMV status, showed an increased
incidence of CMV disease (8 of 9 [88.9%] vs. 3 of 8 [37.5%]; P < .05) and severe
infectious complications (8 of 9 [88.9%] vs. 2 of 8 [25%]; P < .02). In
conclusion, indeterminate result of QF-CMV or interferon-gamma <3.5 IU/mL in
mitogen tube seems to be related to impaired immunity. The QF-CMV assay appears
to be a useful tool in clinical practice, identifying the group of KTRs with
increased risk of infectious complications who may benefit from immunosuppression
reduction and maintenance of antiviral prophylaxis.
PMID- 27496466
TI - Associations of Selected Cytokines Levels in Organ Transplant Recipients Without
and With Malignant Skin Neoplasms.
AB - INTRODUCTION: Skin malignancies are the most prevalent neoplasms seen in organ
transplant recipients (OTRs). Immunosuppressive treatment has been attributed to
play a causative role in malignancy development. The aim of the study was to
assess cytokine concentrations involved in cytotoxic and regulatory responses in
patients after organ transplantation (Tx). We compared two OTR subgroups: those
with malignant skin tumors and those without any known changes developed after
Tx. MATERIALS AND METHODS: We enrolled 102 patients, 63: 3-360 (median: min-max)
months after Tx, aged 54.3 +/- 9.9 (mean +/- SD) years (38.2% females). Seventeen
patients were diagnosed with malignant skin neoplasms. The most frequent
treatment schemes were cyclosporine A - mycophenolate mofetil -
glucocorticosteroids (GS) (37.4%), mycophenolate mofetil-tacrolimus - GS (15.2%),
and azathioprine-cyclosporine A-GS (14.1%). A 5-mL sample of venous blood was
obtained from participants of two subgroups: those with malignant skin tumors and
those without any known changes. The blood was tested for interleukin 2 (IL-2),
interferon gamma, IL-10, and transforming growth factor beta concentrations
(Multicytokine Flex Set, ELISA). The Kruskal-Wallis test was used to compare
variables; P < .05 was considered valid. RESULTS: Age, gender distribution, and
time from transplantation did not differ across the two subgroups. We found
significantly lower blood concentrations of IL-2 and IL-10 in patients with post
transplantation skin cancers versus patients without any known skin changes (0
pgmL(-1) vs. 21.22 pgmL(-1), and 4.93 pgmL(-1) vs. 7.36 pgmL(-1), respectively).
The differences between interferon gamma and transforming growth factor beta
levels were insignificant across studied groups. CONCLUSIONS: Our findings
suggest that immunosuppressive response assessed by cytokine IL-2 and IL-10
levels may be used in the risk stratification for the development of skin cancer
in organ recipient patients.
PMID- 27496467
TI - Benign Cutaneous Disease Among Polish Renal Transplant Recipients.
AB - BACKGROUND: Organ transplant recipients are an at-risk group for skin cancers and
benign cutaneous diseases. Immunosuppression type, dosage, and treatment length
dictates the frequency of benign lesions. MATERIAL AND METHODS: Two hundred
twenty-three consecutive adult renal transplant recipients (RTRs) were enrolled
and screened for benign skin lesions. During examination, swabs, skin scrapings,
and nail clippings were collected from any suspected areas infection and any
cutaneous lesions marked for quality and quantity on a special questionnaire. The
aim was to examine the prevalence of benign cutaneous disease and risk factors.
RESULTS: Fungal infections were the most common infections found (60%), most
commonly in the oral cavity (40.8%). Viral warts occurred in 18.4%, being
significantly more common in those transplanted over 5 years (P = .002).
Hypertrichosis was the most common pilosebaceous disorder found (P <= .001).
Other iatrogenic cutaneous effects included purpura (50.2%), xerosis (41.2%), and
gingival hyperplasia (28.2%), the latter strongly associated with cyclosporine (P
= .0005). Seborrhoeic warts (23.8%) were most common in patients older than 50
years (P < .001). One-third of subjects had skin tags (31%). DISCUSSION: This is
the largest study of the prevalence and type of non-malignant cutaneous diseases
in Polish RTRs. We see increasing numbers of patients with long-term side effects
from immunosuppressive therapy, and treatment, gender, age, and time since
transplantation should be considered with new skin lesions in everyday practice
with RTRs. CONCLUSIONS: The study group had a high prevalence of benign cutaneous
diseases and these should not be overlooked as they can cause aesthetic problems
and reduced quality of life.
PMID- 27496468
TI - Past Cardiovascular Episodes Deteriorate Quality of Life of Patients With Type 1
Diabetes and End-stage Kidney Disease After Kidney or Simultaneous Pancreas and
Kidney Transplantation.
AB - BACKGROUND: The beneficial influence of kidney (KTx) or simultaneous pancreas and
kidney transplantation (SPK) on quality of life (QOL) in patients with end-stage
kidney disease caused by type 1 diabetes mellitus was confirmed in many studies.
The aim of this study was to identify factors that influence QOL of patients in
long-term follow-up after SPK or KTx. METHODS: Twenty-seven SPK and 26 KTx
patients with good function of transplanted organs at least 1 year after
transplantation were enrolled into the analysis. To estimate QOL of the
recipients the Kidney Disease and Quality of Life Short Form was applied.
RESULTS: Within the whole analyzed group, the necessity of exogenous insulin
administration correlated (P < .05) with symptom/problem list (gamma = -0.35),
effects of kidney disease (-0.38), cognitive function (-0.47), sleep (-0.42),
overall health (-0.47), physical functioning (-0.61), role-physical (-0.32), pain
(-0.50), general health (-0.32), emotional well-being (-0.31), role-emotional (
0.36), social function (-0.33), energy/fatigue (-0.44), and the SF-12 physical
composite (-0.44). History of cardiovascular episode correlated (P < .05) with
symptom/problem list (gamma = -0.59), effects of kidney disease (-0.46), burden
of kidney disease (-0.56), sleep (-0.54), social support (-0.51), physical
functioning (-0.55), role-physical (-0.70), pain (-0.60), general health (-0.57),
emotional well-being (-0.45), role-emotional (-0.95), social function (-0.58),
energy/fatigue (-0.59), SF-12 physical composite (-0.45), and SF-12 mental
composite (-0.83). CONCLUSIONS: Exogenous insulin administration and history of
cardiovascular episode are the most important factors influencing QOL in patients
after SPK or KTx, particularly worsening its physical components.
PMID- 27496469
TI - Surgical Complications Not Related to the Renal and Pancreatic Grafts After
Simultaneous Kidney and Pancreas Transplantation.
AB - BACKGROUND: Simultaneous pancreas and kidney transplantation (SPKTx) is the most
commonly performed multiorgan transplantation procedure worldwide. Transplanted
organs are the main source of complication; however, some postoperative
complications are not directly related to the pancreatic or renal grafts. The
goal of this study was to evaluate the prevalence, type, and severity of
postoperative complications not related to transplanted kidney or pancreas among
SPKTx recipients. METHODS: Complications unrelated to transplanted pancreas and
kidneys among 112 SPKTx recipients were analyzed. The cumulative freedom from
general surgical complications was assessed, and it was compared with cumulative
freedom from complications related to kidney and pancreatic grafts. Severity of
complications was classified according to a modified Clavien-Dindo scale.
RESULTS: The general surgery complication rate was 22.2%. Cumulative freedom from
general surgical complications at days 60 and 90 after transplantation was 0.89
and 0.87, respectively. Cumulative freedom from general surgical complications
was comparable with cumulative freedom from complications related to kidney
grafts but significantly higher than cumulative freedom from complications
related to pancreatic grafts (log-rank test, P < .001). The rates for grades of
severity II, IIIa, IIIb, and IVb were 19.4%, 9.7%, 64.5%, and 6.4%, respectively.
The most frequent cause of complications was intra-abdominal hematoma or abscess
(25.8%). CONCLUSIONS: The general surgical complication rate was comparable to
the rate of complications originating from the renal grafts but significantly
lower than the complication rate related to the transplanted pancreas. The
incidence of general surgical complications could be defined as moderate, and the
severity of this type of complication was low.
PMID- 27496470
TI - Usefulness of Modified Dindo-Clavien Scale to Evaluate the Correlation Between
the Severity of Surgical Complications and Complications Related to the Renal and
Pancreatic Grafts After Simultaneous Kidney and Pancreas Transplantation.
AB - OBJECTIVE: Simultaneous pancreas and kidney transplantation (spktx) is the
multiorgan transplantation. Thus various complications originated from
transplanted organs and the complications that are not directly related to
pancreatic or renal grafts could be developed at the same recipient. AIM: The aim
of this study is to explore whether there is a correlation between the severity
of complications originated from transplanted pancreas, transplanted kidney and
general surgical complication developed at the same spktx recipient. METHODS:
Complications which developed among 112 spktx recipients were divided into three
groups: related to the pancreatic graft (PTXc), to the renal graft (KTXc) and the
general surgical complication (GNc). Severity of postoperative complications
using modified Dindo-Clavien scale recipients was evaluated for each group. The
correlation of severity of coexisting complications from different complication
groups was analyzed. RESULTS: There were 22 recipients who developed the
coexistence of complication between different complication groups. Complication
originated from two and three complication groups developed 15 (68.2%) and 7
(31.8%) patients, respectively. There was not found correlation of the
complication severity between: KTXc and GNc group, GNc and PTXc group, KTXc and
PTXc group. The correlation (r = 0.84) of complication severity in recipients who
developed concurrently complication from transplanted kidney, transplanted
pancreas and general surgery complication was found. CONCLUSION: The modified
Dindo-Clavien scale is an useful methodology for the correlation description of
complication severity in complex multiorgan transplantation such is spktx,
especially when the complications originated from different, potentially
independent from the pathophysiological point of view, sources.
PMID- 27496471
TI - Long-Term Outcomes of Kidney and Simultaneous Pancreas-Kidney Transplantation in
Recipients With Type 1 Diabetes Mellitus: Silesian Experience.
AB - BACKGROUND: Kidney transplantation (KTx) markedly reduces mortality in patients
with end-stage kidney disease (ESKD) caused by type 1 diabetes mellitus (T1DM).
The outstanding issue is whether transplantation should be limited only to KTx,
with further insulinotherapy, or combined with pancreas transplantation in
patients with ESKD/T1DM. The goal of this study was to compare the results of
simultaneous pancreas-kidney transplantation (SPKTx) and deceased donor KTx and
to identify factors affecting patient and kidney graft survival in patients with
ESKD/T1DM. METHODS: Eighty-seven deceased donor KTx and 66 SPKTx operated on in
the Silesia region of Poland between 1998 and 2013 were included in the
retrospective analysis. RESULTS: During the mean 6.7 +/- 3.6 years of follow-up,
fewer cardiovascular episodes were observed in SPKTx recipients than in KTx
recipients (1.5% vs 12.6%; P < .05). Five-year patient survival (80.7% in SPKTx
vs 77.5% in KTx) and kidney graft survival (66.1% in SPKTx vs 70.4% in KTx) did
not differ between study groups. There were no differences in patient survival
(log-rank test, P = .99) or kidney graft survival (P = .99) based on Kaplan-Meier
curves. Multivariable Cox proportional hazard analysis failed to identify factors
explaining patient and kidney graft survival. Five-year pancreas graft survival
was 58.9%. SPKTx recipients had significantly higher estimated glomerular
filtration rates during the 7-year posttransplant period and less frequently
developed proteinuria (6.1% vs 23%; P < .01). CONCLUSIONS: Pancreas
transplantation reduced cardiovascular risk and prevented the development of
proteinuria but did not improve patient and kidney graft survival in recipients
with T1DM in the 7-year follow-up period.
PMID- 27496472
TI - Profile of Gut Microbiota Associated With the Presence of Hepatocellular Cancer
in Patients With Liver Cirrhosis.
AB - BACKGROUND: Changes within the gut microbiota contribute to the progression of
chronic liver diseases. According to the results of several studies performed in
animal models, gut dysbiosis plays an important role in hepatocarcinogenesis. The
aim of this study was to explore the characteristics of gut microbiota associated
with the presence of hepatocellular cancer (HCC) in patients with cirrhosis of
the liver undergoing liver transplantation. METHODS: A total of 15 patients with
HCC and 15 non-HCC patients matched according to etiology of cirrhosis and Model
for End-Stage Liver Disease (MELD) scores who underwent liver transplantations
between 2012 and 2014 were included. Analysis of their gut microbial profile was
based on prospectively collected stool samples from the pretransplant period.
RESULTS: Patients with and without HCC were similar with respect to age (P =
.506), sex (P = .700), hepatitis C virus (P > .999) and hepatitis B virus (P =
.715) infection status, alcoholic liver disease (P > .999), and MELD score (P =
.337). Notably, the presence of HCC was associated with significantly increased
fecal counts of Escherichia coli (P = .025). Prediction of HCC presence based on
E coli counts was associated with the area under the receiver-operating curve of
0.742 (95% confidence interval, 0.564-0.920), with the optimal cutoff on the
level of 17.728 (natural logarithm of colony-forming units per 1 g of feces).
Sensitivity and specificity rates for the established cutoff were 66.7% and
73.3%, respectively. CONCLUSIONS: The profile of gut microbiota associated with
the presence of HCC in cirrhotic patients is characterized by increased fecal
counts of E coli. Therefore, intestinal overgrowth of E coli may contribute to
the process of hepatocarcinogenesis.
PMID- 27496473
TI - Factors Affecting Breathing Capacity and Early Tracheal Extubation After Liver
Transplantation: Analysis of 506 Cases.
AB - BACKGROUND: Early extubation is a standard procedure after liver transplantation
(LT). METHODS: The preoperative and perioperative data of 506 adult patients
undergoing LT from July 2000 to March 2015 were analyzed. The goal of this study
was to determine preoperative and perioperative independent predictors of early
tracheal extubation. RESULTS: Of the 506 study patients, 73.7% were extubated
early after LT. Patients in this group exhibited better preoperative and
perioperative outcomes. However, according to multivariate logistic regression
analysis, only 3 parameters were independent predictors of early extubation:
initial hemoglobin concentration (odds ratio [OR], 1.187 [95% confidence interval
(CI), 1.033-1.364]), application of epidural anesthesia (OR, 2.762 [95% CI, 1.025
7.445), and units of perioperative packed red blood cells and fresh frozen plasma
transfused (OR, 0.919 [95% CI, 0.888-0.952]). CONCLUSIONS: Early extubation of
patients undergoing LT is a safe and widely used procedure. However, the decision
regarding this procedure should be made after thorough analysis of the patient's
current status, the course of operation, and the patient's preoperative
parameters. Based on our findings, we believe that the decision regarding early
extubation can be aided by taking into account the patient's initial hemoglobin
concentration, the number of packed red blood cells and fresh frozen plasma
transfused during surgery, and pain control by application of a thoracic epidural
catheter.
PMID- 27496474
TI - Assessment of the Quality of Life in Patients After Liver Transplantation as an
Important Part of Treatment Results.
AB - INTRODUCTION: Organ transplantation for many patients with end-stage liver
disease is a life-saving operation. Progressing at a time and usually
irreversible damage to the organ directly leads to many life-threatening
complications as well as to progressive deterioration in health and the quality
of life (QOL). On the other hand, the assessment of QOL after liver
transplantation, apart from the survival analysis, should take into account
general health perception, physical activity, a place in the family and in the
environment, as well as the patient's social and professional activity. MATERIAL
AND METHODS: The study group included 238 patients (128 women and 110 men) who
underwent transplantation in various transplantation centers in Warsaw due to
chronic and acute liver failure. To measure the QOL the author's questionnaire
was used, which was made especially for this study. RESULTS: There were no
significant correlations found between the subjective QOL of the examined
patients and socio-demographic and clinical variables, such as age, gender,
education, marital status, occupational status, and time from the organ
transplantation. However, a significant correlation was found between the
perceived QOL of patients and the following variables: physical activity, pain
and other symptoms, social and family life, sex life, and psycho-emotional state.
It was also proved that the problems with maintaining a normal body weight after
liver transplantation significantly affected the overall health of patients.
CONCLUSIONS: Liver transplantation in the vast majority of patients, despite
numerous complaints, facilitates functioning in various fields of life. On the
other hand, the indicated discomfort in the area of mental and emotional health
requires easier access to a psychologist. At the same time, there is a justified
requirement for education and nutritional counselling for patients after liver
transplantation because of the proven risk of occurrence of cardiovascular
disease.
PMID- 27496475
TI - Predictive Value of the Model for End-Stage Liver Disease Score Excluding
International Normalized Ratio One Year After Orthotopic Heart Transplantation.
AB - BACKGROUND: The Model for End-Stage Liver Disease (MELD) scoring system
incorporating a combination of hepatic and renal laboratory parameters does not
adequately reflect the degree of multi-organ dysfunction in patients with heart
failure, who need oral anticoagulation. In order to exclude the impact of oral
anticoagulation on the international normalized ratio (INR), we used the MELD
excluding INR (MELD-XI) score. The aims of the study were to calculate the
individual preoperative MELD-XI score and its ability to predict 1-year mortality
after heart transplantation and to identify other preoperative laboratory
prognostic parameters. METHODS: We retrospectively analysed data of 87
consecutive adults undergoing heart transplantation between 2011 and 2014.
Clinical data and laboratory parameters for the calculation of the MELD-XI score
were obtained at the time of admission for the heart transplantation. RESULTS:
The average age of the patients was 48.8 +/- 13.3 years and 68.9% of them were
male. During the observation period, the mortality rate was 18.4%. Multivariate
analysis of Cox proportional hazard confirmed that the pretransplantation MELD-XI
score (hazard ratio [HR] = 1.625 [1.286-2.053]; P < .001), sodium serum
concentration (HR = 0.824 [0.677-1.001]; P < .05) and highly sensitive C-reactive
protein (hs-CRP) serum concentration (HR = 1.045 [1.008-1.083]; P < .02) were
independent predictors of death during the first year after heart
transplantation. Area under the receiver operating characteristic (ROC) curve
(AUC) indicated a good discriminatory power of MELD-XI (AUC 0.997; P < .04) and
plasma sodium concentration (AUC 0.901; P < .01) in death prediction.
CONCLUSIONS: Our study confirms that the pretransplantation MELD-XI score, as
well as serum sodium and hsCRP concentrations, may be used to estimate
postoperative risk in heart transplant recipients during a 1-year follow-up.
PMID- 27496476
TI - Liver Transplantation for Incurable Alveolar Echinococcosis: An Analysis of
Patients Hospitalized in Department of Tropical and Parasitic Diseases in Gdynia.
AB - INTRODUCTION: Alveolar echinococcosis is a parasitic disease caused by the larval
stage of tapeworm Echinococcus multilocularis. It usually involves the liver, but
can spread to other organs. The treatment of choice is a surgical resection
supported by antiparasitic drugs. In the advanced stages of the disease a liver
transplantation is the only option. AIM: This article presents the problems
related to care of patients after liver transplantation for advanced alveolar
echinococcosis. MATERIAL: Sixty-seven patients with alveolar echinococcosis were
hospitalized in our clinic in the years 2000-2015. Liver transplantation has been
a therapeutic option for 9 patients. We retrospectively analyzed data of
qualification for the liver transplantation and the postoperative treatment.
RESULTS: Follow-up time after liver transplantation ranged from 7 months to 155
months (average, 6.4 years). One patient, with a history of advanced disease
(P4N1M0), died due to liver failure. One patient was lost to follow-up. After
liver transplantation all patients were receiving albendazole treatment. Two
patients did not follow the medical recommendations. In 1 patient, who decided to
stop therapy after 1 year, the relapse of alveolar echinococcosis in the left
lobe of the transplanted liver passing through the diaphragm to the pericardium
was detected. In another case we suspected a relapse of alveolar echinococcosis
in transplanted liver due to positive serological tests. CONCLUSION: The
prognosis of patient after liver transplantation for alveolar echinococcosis is
good. The main problem caused by immunosuppressive therapy is a recurrence of
disease in the transplanted liver.
PMID- 27496477
TI - Outcomes of Patients With Poorly Differentiated Hepatocellular Carcinoma After
Liver Transplantation.
AB - BACKGROUND: Liver transplantation (LT) outcomes for patients with poorly
differentiated (G3) hepatocellular carcinoma (HCC) are unsatisfactory. The aim of
this study was to evaluate outcomes in patients with poorly differentiated HCC
undergoing LT. PATIENTS AND METHODS: There were 192 HCC patients after LT in the
Department of General, Transplant and Liver Surgery, Medical University of
Warsaw, between January 2001 and April 2014. The study group comprised 24
patients with poorly differentiated tumors. RESULTS: Disease-free survival (DFS)
for all patients was 49.5% at 5 years. The 5-year DFS for patients who met the
Milan criteria (n = 9, 88.9%) was significantly better compared to those who did
not (n = 15, 28.0%, P = .025). Multivariable analysis revealed that only the
largest tumor diameter (P = .014) and alpha-fetoprotein (AFP) concentration (P =
.001) were independent risk factors for DFS. The optimal cut-off AFP and tumor
size that could distinguish patients with the highest risk were >=500 ng/mL and
>=3.5 cm, respectively. DFS for patients with AFP <500 ng/mL and tumor size <3.5
cm was 100% after 2.8 years, and for those with >=500 ng/mL or tumor size >=3.5
cm was 46.9% after 5 years. However, the DFS for patients with AFP >=500 ng/mL
and tumor size >=3.5 cm was only 12.5% after 4.7 years (P = .002). CONCLUSIONS:
Outcomes of patients with poorly differentiated HCC treated with LT can be
characterized with acceptable survival when applying criteria based on tumor size
<3.5 cm and AFP <500 ng/mL.
PMID- 27496478
TI - Prognostic Factors and Outcomes of Patients After Liver Retransplantation.
AB - BACKGROUND: Despite great progress and improvement in results of orthotopic liver
transplantation (OLTx), 10%-20% of patients still require retransplantation (re
OLTx). The aim of the study was to present long-term results of liver
retransplantation and to determine the factors influencing outcomes. PATIENTS AND
METHODS: From December 1994 to July 2014, a total of 1461 liver transplantations
were performed in the Department of General, Transplant and Liver Surgery of
Medical University of Warsaw. There were 92 retransplantations (6.3%), including
40 early re-OLTx (up to 30 days). The most common indication for re-OLTx were
vascular complications (41/92, 44.6%). Influence of clinical variables on short-
and long-term outcomes was analyzed. RESULTS: Postoperative mortality was 30.4%
(28/92). One-year, 3-year and 5-year survival for all patients was 59.8%, 56.5%
and 54.1%, respectively. The best results were achieved in patients undergoing
retransplantation due to chronic rejection and biliary complications, whose 5
year survival rates were 75.0% and 72.9% respectively. There was no difference in
long-term survival after early and late retransplantations (60.9% and 49.3%,
respectively; P = .158). Multivariable analysis revealed factors associated with
longer survival of patients, namely, higher preoperative hemoglobin concentration
(P = .001), increased blood transfusions (P = .048), and decreased fresh frozen
plasma transfusions (P = .004). CONCLUSIONS: Liver retransplantation is a method
providing satisfactory outcomes in selected patients. The perioperative period
has a major impact on patient outcome.
PMID- 27496479
TI - High Frequency of Arterial Hypertension in Patients After Liver Transplantation.
AB - BACKGROUND: Cardiovascular diseases are among the most frequent causes of patient
death after liver transplantation. The aim of this retrospective clinical study
was to estimate the prevalence of arterial hypertension among patients after
successful liver transplantation and the role of immunosuppressive drugs in the
pathogenesis of hypertension in these patients. PATIENTS AND METHODS: A total of
88 patients (age 47 .5 +/- 12.1 years; 33 women and 55 men) who had undergone
successful liver transplantation and completed 24 months follow-up were studied.
The results are presented as means with standard deviations. RESULTS: At 1, 12,
and 24 months after liver transplantation, the prevalences of hypertension were
44.3%, 54.5%, and 62.5%, respectively. Systolic and diastolic blood pressure in
these months were 124.1 +/- 14.8, 132.8 +/- 19.1, and 135.2 +/- 17.3 mm Hg and
83.3 +/- 12.0, 87.3 +/- 11.1, and 87.9 +/- 11.1 mm Hg, respectively. The
estimated glomerular filtration rates were 77.8 +/- 32.3, 80.3 +/- 30.8, and 78.8
+/- 29.1 mL/min/1.73 m(2), respectively. Arterial hypertension was significantly
more frequent in patients treated with cyclosporine A than in those treated with
tacrolimus (P = .004) or everolimus (P = .005). In patients treated with
tacrolimus, a positive correlation was found between tacrolimus blood
concentration and systolic blood pressure (R = 0.34; P = .01) and a negative
correlation was found between estimated glomerular filtration rate and systolic
blood pressure (R = -0.28; P = .02). CONCLUSIONS: Based on study findings, the
following conclusions were drawn: arterial hypertension occurs in more than 50%
of patients after liver transplantation (significantly higher frequency than in
the general population); calcineurin inhibitors may participate in the
pathogenesis of arterial hypertension in patients after successful liver
transplantation; and the clinical importance of these findings and the influence
on cardiovascular outcome of the liver transplant recipients need further
investigation.
PMID- 27496480
TI - Dynamic Elastography in Diagnostics of Liver Fibrosis in Patients After Liver
Transplantation Due to Cirrhosis in the Course of Hepatitis C.
AB - BACKGROUND: Assessment of the dynamics and degree of liver fibrosis in patients
after liver transplantation is a basic element in the process of determining
transplant survival prognosis. It allows planning and early initiation of
prophylaxis or treatment, which translates into increased chances of preventing
cirrhosis and of long-term optimal function of the graft. The aim of this study
was to compare the results of biopsy and dynamic elastography in diagnostics of
transplanted liver fibrosis, as well as determination of the stiffness cut-off
point for assessment of significant fibrosis. PATIENTS AND METHODS: The study
included 36 patients who had undergone liver transplantation due to cirrhosis in
the course of hepatitis C virus (HVC) infection. Fibrosis was assessed in
bioptates according to the METAVIR score (F0-F4). Elastography was performed
using FibroScan; receiver operating characteristic curve analysis was used to
identify the cut-off point for significant fibrosis (>=F2). RESULTS: The median
stiffness in kPa for the whole group F0-F4 was 6.3 (range 3.4-29.9); for >=F2 it
was 6.9 (3.4-29.9), whereas for F0-F1 it was 4.4 (3.5-8.0). It was demonstrated
that the value of 4.7 kPa in elastography is a statistically significant cut-off
point for differentiation between the groups F0-F1 and F2-F4 (sensitivity: 93%,
specificity: 57%, positive predictive value: 90%, negative predictive value:
66%), area under the receiver operating characteristic curve: 0.746 (95%
confidence interval: 0.53-0.95, P < .05). CONCLUSIONS: Elastography is a
promising tool for noninvasive assessment of significant liver fibrosis in
patients after transplantation due to cirrhosis in the course of hepatitis C; it
allows reduction in the number of biopsies performed.
PMID- 27496481
TI - Hypertension in Pregnant Renal and Liver Transplant Recipients.
AB - BACKGROUND: Pregnancies in transplant recipients involve risks for both grafts
and the fetus, and need to be carefully managed. Hypertension is the most
frequent complications in pregnant transplant recipients, especially in renal
transplant recipients. Strict control of blood pressure is essential for a
favorable obstetric outcome and long-term graft survival. The aim of the study
was to evaluate the influence of hypertension on obstetric outcome and graft
function in pregnant renal transplant recipients (RTR) or liver transplant
recipients (LTR) in comparison with healthy pregnant women. PATIENTS AND METHODS:
This retrospective analysis included 46 RTR and 55 LTR who delivered between the
years 2000 and 2014. The control group consisted of 187 nontransplant patients
aged 20-45 years who delivered between 2010 and 2013. The analyzed group was
divided into 2 subgroups: patients with hypertension and patients without
hypertension. Descriptive data analysis, Fisher Exact test, unpaired Student t
test, and analysis of the variance were performed. RESULTS: Hypertension
prevalence among the RTR, LTR, and control group was 73.5%, 34.5%, and 4.3%
respectively. In the RTR group, the mean gestational age at delivery inp patients
with hypertension vs without hypertension was 36 vs 34.5 weeks (P < .05); IUGR
was diagnosed in 20% vs 8.5% pregnant women (P > .05). In the TRL group, the mean
gestational age at delivery in group with hypertension vs without hypertension
was 37 vs 3.9 weeks (P < .05); IUGR was diagnosed in 10.5% vs 5% of pregnant
women (P > .05). Hypertension in RTR patients had a negative influence on graft
function (P > .05). CONCLUSION: Hypertension is common in organ recipients, and
is associated with adverse pregnancy outcomes and loss of graft function.
PMID- 27496483
TI - Predictors of Tricuspid Valve Anulus Dilation in a Heart Recipient Population.
AB - BACKGROUND: Tricuspid valve regurgitation in reported in >20% of heart
recipients. It severity has not only clinical impact, but it is also associated
with increased mortality. Risk factors for developing tricuspid valve dysfunction
include allograft rejection, donor/recipient pericardial cavity mismatch,
preoperative transpulmonary gradient and vascular resistance, biatrial
anastomosis technique, and biopsy-induced injury. Tricuspid valve annulus
distention is reported to causative factor for most common type of tricuspid
valve dysfunction after heart transplantation. The aim of the study was to
estimate possible early predictors for tricuspid valve regurgitation after
orthotopic heart transplantation performed with standard Lower-Shumway technique
on magnetic resonance imaging studies. METHODS: A total of 20 patients (18 men
and 2 women) with a mean age of 45 +/- 12 years were enrolled into the study.
Echocardiographic evaluation followed by magnetic resonance studies were
performed. The mean duration from time of transplantation was 34 +/- 12 months.
Magnetic resonance and echocardiographic imaging focused on tricuspid valve
annulus diameter and atrium dimensions. RESULTS: The was a progressive distension
of tricuspid valve annulus observed during the follow-up period. Mean tricuspid
valve diameter increased from 3.0 +/- 0.3 to 3.34 +/- 0.3 mm (P < .05). There was
a positive correlation observed between recipient native right atrium and overall
right atrium diameter and tricuspid valve diameter distension. CONCLUSIONS:
Overall right atrium diameter and native recipient right atrium diameter were
found to be a risk factor for tricuspid valve annulus distension.
PMID- 27496482
TI - Perioperative Risk Factors of Cardiac Allograft Vasculopathy in the Long-Term
Follow-up.
AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) still remains to be one of the
most important limiting factors for heart transplant recipients' long-term
survival. The aim of our study was to identify the perioperative risk factors
impacting the occurrence of CAV during the long-term follow-up. METHODS: We
retrospectively analysed the data from 198 consecutive adult patients, who
underwent heart transplantation between 2007 and 2012, in whom at least one
routine coronarography (CAG) was performed. CAV onset was defined as any lesion
seen at least at one routine CAG. RESULTS: The average follow-up was 63.6 +/-
14.7 months. The frequency of CAV in the analysed population was 36 (18.1%).
Multivariate stepwise logistic regression analysis confirmed that NT-proBNP
plasma concentration directly before heart transplant [logNT-proBNP OR = 16.455
(4.587-31.036), P < .0001], fibrinogen plasma concentration a month after heart
transplant [OR = 1.022 (1.009-1.035), P < .001] and occurrence of diabetes [OR =
12.355 (1.417-35.750), P < .001], were independent predictors of CAV. Area under
the ROC curves (AUC) indicated a well discriminatory power of plasma fibrinogen
[AUC 0.9278, P < .001] and plasma NTproBNP concentration [AUC 0.9514, P < .001]
in CAV prediction. The optimal cut-off value of fibrinogen was 509 mg/dL, and of
NT-proBNP was 10080 pg/mL. CONCLUSIONS: Our data show that NT-proBNP and
fibrinogen plasma concentrations as well as occurence of diabetes, both
preexisting and new onset after heart transplant can be used to identify patients
at risk of developing CAV.
PMID- 27496484
TI - BRCA1 Reflects Myocardial Adverse Remodeling in Idiopathic Dilated
Cardiomyopathy.
AB - BACKGROUND: The role of BRCA1 in chronic ischemic episodes seems to be pivotal
for adverse remodeling and development of ischemic cardiomyopathy, because of its
role in DNA repair and apoptosis. The aim of this study was to investigate the
role of BRCA-1 in idiopathic dilated cardiomyopathy (IDCM). MATERIAL AND METHODS:
The study group (IDCM) comprised myocardial samples from hearts explanted before
transplantation owing to IDCM in 10 males (age 44 +/- 5.3 years) without clinical
symptoms of ischemic heart disease. The control group consisted myocardial
fragments taken from 10 male heart valve and pulmonary artery donors with
diagnosed cerebral death (age 40 +/- 2.3 years). BRCA1 was detected
immunohistochemically with rabbit anti-BRCA1 polyclonal antibody. The intensity
of BRCA1 expression was semiquantitatively assessed for cardiocytes, small
vessels including capillaries, and interstitial cells. The significances between
groups were estimated using the Mann-Whitney U test. RESULTS: All IDCM cases were
positive and presented nonuniform BRCA1 expression: hypertrophied cardiocytes
showed very intense staining and typical cardiomyopathic cardiocytes were stained
weakly forming mosaic. Control cases showed weak-to-moderate uniform staining.
Intensity of staining was significantly higher in IDCM cardiocytes, whereas small
vessels and interstitial were stained similarly in both groups. CONCLUSIONS: IDCM
adverse remodeling results in more intense but nonuniform BRCA1 expression. This
phenomenon seems to reflect IDCM biology: lower BRCA1 expression in myocytes with
lower anti-apoptotic and DNA damage repair activity, with the opposite in
hypertrophied myofibers.
PMID- 27496485
TI - High-performance Liquid Chromatography Measured Metabolites of Endogenous
Catecholamines and Their Relations to Chronic Kidney Disease and High Blood
Pressure in Heart Transplant Recipients.
AB - BACKGROUND: Patients after solid organ transplantation, especially heart and
kidneys, are prone to be hypertensive. Recently chronic kidney disease and
renalase metabolism of endogenous catecholamines are thought to make major
contribution to the pathogenesis of hypertension. MATERIALS AND METHODS: We
analyzed 75 heart recipients (80% male, 20% female), medium age 54.9 years
(range, 25-75) at 0.5 to 22 years after heart transplantation (median, 10.74).
Diagnosis of hypertension was made on the basis of ambulatory blood pressure
monitoring. Complete blood count, urea, creatinine, estimated glomerular
filtration rate (eGFR), renalase in serum, and levels of metanefrine,
normetanefrine, and 3-metoxytyramine in 24-hour urine collection calculated with
a high-performance liquid chromatography were recorded. RESULTS: Urine endogenous
catecholamine metabolites were estimated according to creatinine clearance.
Normetanefrine was correlated with age (r = 0.27; P < .05), urea (r = 0.64; P <
.01), creatinine (r = 0.6; P < .01), eGFR (r = -0.51; P < .01), renalase (r =
0.5; P < .01), and diastolic blood pressure (r = 0.26; P < .05). Metanefrine was
correlated with urea (r = 0.43; P < .01), creatinine (0.32; P < .01), eGFR (r =
0.4; P < .01), renalase (r = 0.34; P < .05), height (r = -0.26; P < .05), weight
(r = -0.23; P < .05), and time after heart transplantation (r = 0.27; P < .05). 3
Metoxytyramine was correlated with urea (r = 0.43; P < .01), creatinine (r =
0.32; P < .01), and the eGFR (r = -0.24; P < .05). Creatinine was correlated with
age (r = 0.36; P < .01), diastolic blood pressure (r = 0.26; P < .05), time after
heart transplantation (r = 0.24; P < .05), and renalase (r = 0.69; P < .01).
Systolic blood pressure was correlated with proteinuria (r = 0.26; P < .05).
CONCLUSIONS: Chronic kidney disease and concomitant hypertension are the most
prevalent comorbidities in the population of heart transplant recipients. Urine
catecholamine metabolites were related to kidney function but not to blood
pressure level in the studied population.
PMID- 27496486
TI - Predictive Value of Hepatic and Renal Dysfunction Based on the Models for End
Stage Liver Disease in Patients With Heart Failure Evaluated for Heart
Transplant.
AB - BACKGROUND: The evaluation of prognosis and determination of a long-term
treatment strategy is an important element of management in patients with heart
failure (HF). METHODS: The aim of the study was to determine the prognostic value
of the Model for End-Stage Liver Disease (MELD) and its modifications, MELD and
serum sodium (MELD-Na) and MELD excluding the international normalized ratio
(MELD-XI), as well as other independent risk factors for death during a 4-year
follow-up. We analyzed retrospectively 143 patients with advanced HF, evaluated
for heart transplant between 2009 and 2011. Patients using warfarin were excluded
from the study. The long-term follow-up data were obtained during follow-up
visits and/or phone contact with the patients or their families. RESULTS: The age
of the patients was 54 (48-59) years and 88.1% of patients were male. Mortality
rate during the follow-up period was 49%. The MELD scores (hazard ratio [HR],
1.12; P < .001), as well as serum high-sensitivity C-reactive protein (hs-CRP;
HR, 1.01; P < .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; HR,
1.01; P < .05) levels, were independent risk factors for death. Receiver operator
characteristic analysis indicated that a MELD cutoff of 10 (area under the curve
[AUC], 0.756; P < .0001], MELD-XI cutoff of 13.0 (AUC, 0.720; P < .0001), MELD-Na
cutoff of 13.0 (AUC, 0.813; P < .0001), hs-CRP cutoff of 4.02 (AUC, 0.686; P <
.001), and NT-proBNP cutoff of 1055 (AUC, 0.722; P < .001) were the best
predictive values as predictors of death. CONCLUSIONS: MELD, MELD-Na, and MELD-XI
scores are prognostic factors for death during a 4-year follow-up. A high MELD
score is an independent prognostic factor for death. NT-proBNP and hs-CRP serum
concentrations are other independent factors influencing death.
PMID- 27496487
TI - Role of Personal Resources in Depression and Stress in Heart Transplant
Recipients.
AB - BACKGROUND: Heart transplantation is the primary option for heart failure
treatment and increases the survival rate and the quality of life for recipients.
However, this surgical intervention induces numerous psychological problems, such
as depression and anxiety. Protective factors and personal recourses are a
significant force behind healthy adjustment to life stresses. The aim of this
study was to assess the role of personal recourses in terms of depression and
stress in heart transplant recipients. METHODS: The study involved a sample of
131 post-heart transplant patients. Standardized instruments were used to measure
the key constructs: Beck Depression Inventory Short Form for prevalence of
depression, Perceived Stress Scale for prevalence distress, and Sense of
Coherence (SOC-29), Life Orientation Test, and General Self-Efficacy Scale for
measuring personal resources. RESULTS: We found that sense of coherence,
optimism, and self-efficacy proved to be significant predictors for the
prevalence of both depression and stress. CONCLUSIONS: These result suggest that
the assessment of coping strategies and sense of coherence in heart transplant
recipients requires exploration. Evaluating coping strategies and sense of
coherence before surgery seems significant and begins with developing skills in
this domain.
PMID- 27496488
TI - Lack of Impact of Presence of Positive C4d Staining in Capillaries in Myocardial
Biopsies on Long-term Survival of Heart Transplant Patients.
AB - BACKGROUND: The long-term survival of 209 consecutive patients (mean age, 46 +/-
15 years) from a single center with >=1 diagnostic myocardial biopsy after heart
transplantation was analyzed. METHODS: Patients were considered as C4d positive
if a capillary staining (immunohistochemistry in paraffin samples) was observed
in >=1 myocardial biopsy. Data were analyzed according to pathologic consensus of
antibody mediated rejection definition of C4d+ positivity: 2004 definition in
group A and the 2013 definition in group B and compared with their respective
controls, composed of patients who do not meet those criteria. Age, follow-up
time, and number of biopsies were comparable between patients with C4d+ and
controls in both groups. Follow-up was 100% complete with mean of observation
time 2143 days. RESULTS: During the follow-up period, 62 patients died (group A:
C4d+ 32% vs controls 29%; group B: C4d+ 36% vs controls 29% [P = NS]). There were
no differences in survival between patients with positive staining and without
C4d+ staining when Kaplan-Meier survival curves were compared. CONCLUSIONS: The
presence of C4d positive staining in myocardial capillaries of heart biopsies of
patients after heart transplantation, as an isolated finding, was not related to
worse long-term survival.
PMID- 27496489
TI - Comparison of Mechanical Circulatory Support by the Use of Pulsatile Left
Ventricular Assist Devices Polvad MEV and Continuous Flow Heart Ware and Heart
Mate II in a Single-Center Experience.
AB - BACKGROUND: Mechanical circulatory support is increasingly used in patients with
heart failure as a bridge to transplant or recovery. Results of use the Polish
POLVAD MEV pulsatile circulatory support system and its comparison with novel
devices never was done. We compared the course of patients with left ventricular
circulatory support (left ventricular assist device [LVAD]) supported by POLVAD
MEV or continuous flow devices Heart Mate II (HM II) and Heart Ware (HW) in
single-center cohort. METHODS: We retrospectively reviewed 44 patients who
underwent Polvad Mev (group P; n = 24 [21M/3F]) or HW or HM II (group C; n = 20
[20M/0F]) implantation between April 2007 and February 2014. Patients were in
INTERMACS 1 (6 in group P and 1 in group C) or 2. Preimplant demographics, and
perioperative and postoperative clinical outcomes were reviewed between groups.
We analyzed baseline signs of heart failure, comorbidities, complications, and
the 30- and 90-day results. RESULTS: Among the groups, age, gender, weight, and
cause of heart failure were comparable. Patients in group C suffered more
frequently from hypercholesterolemia preoperatively. Patients in group P had more
pulmonary complications (7 vs 0) after LVAD implantation and stay longer on
intensive care unit than patients in group C (17.61 +/- 16.96 vs 9.56 +/- 9.42; P
= .047). After exclusion, INTERMACS 1 patients it was not significant (14.8 +/-
10.8 vs 9.8 +/- 9.6 days; P = .065), the 30- and 90-day mortality was comparable.
CONCLUSIONS: Implantation of pulsatile POLVAD MEV and continuous flow devices as
LVAD support provides comparable results. A greater number of complications in
group P can cause increased mortality over a longer observation period.
PMID- 27496490
TI - Effects of Left Ventricular Assist Device Support on End-Organ Function in
Patients With Heart Failure: Comparison of Pulsatile- and Continuous-Flow Support
in a Single-Center Experience.
AB - BACKGROUND: Limited data exist about the effects of continuous-flow versus
pulsatile-flow left ventricular assist devices (LVADs) on end-organ function. We
hypothesized that a pulsatile Polvad MEV (PM) would result in outcomes similar to
those of similarly ill patients implanted with a continuous-flow LVAD (Heartware
[HW] or Heartmate II [HMII]). We aimed to compare renal, hepatic, and hematologic
functions in the 1st 30 days of support. METHODS: We retrospectively reviewed
patients with 24 PM (21 M, 3 F; group P) and 15 HW and 5 HMII (20 M, 0 F); group
C LVAD implantations from April 2007 to February 2014. Creatinine, bilirubin,
aspartate (AST) and alanine (ALT) transaminases, hematocrit, platelet count,
international normalized ratio (INR), and activated partial thromboplastin time
(APTT) parameters were analyzed before implantation and during 30 days of
support. Demographic parameters were similar. RESULTS: No significant differences
were found between the groups regarding baseline renal, hepatic, or hematologic
function. Baseline INR and APTT were significantly higher in group P. Levels of
creatinine were similar between groups. They increased from baseline to
postoperative day (POD) 1 and then decreased. Bilirubin levels were
insignificantly higher in group P. Transaminases were significantly higher in
group P (AST in PODs 3-6, ALT in PODs 3-7). INR values were significantly higher
at baseline and in POD 0. APTT values were insignificantly higher in group P.
CONCLUSIONS: The use of LVAD improved renal and hepatic function in our series.
Patients in group P had more decreased hepatic function and presented slower
regeneration.
PMID- 27496491
TI - Endocan Concentration and Chronic Inflammatory Process Among Heart Transplant
Recipients.
AB - BACKGROUND: Endocan is a novel soluble dermatan sulfate proteoglycan derived from
endothelium. It has the capacity of binding to different biologically active
molecules associated with cellular signaling, adhesion, and regulating
proliferation, differentiation, migration, and adhesion of different cell types
in health and pathology. Its elevated level is connected with endothelial
activation, neovascularization, and inflammation or carcinogenesis. METHODS: The
level of serum endocan among 131 heart transplant recipients on 3-drug
immunosuppression (calcineurin inhibitor, mycophenolate mofetil/mycophenolic
acid, steroid) in correlation with other markers of endothelial damage was
determined. In addition, 22 healthy volunteers were studied. In cross-sectional
study, markers were measured with the use of commercially available assays of
endothelial damage-endocan and von Willebrand factor (VWF)-inflammation-high
sensitivity C-reactive protein (hsCRP), interleukin (IL) 6-and kidney function
cystatin C. RESULTS: The endocan, VWF, IL-6, hsCRP, and cystatin C levels were
significantly higher in heart transplant recipients compared with healthy
volunteers. In our cohort, endocan level was correlated with renal function
(estimated glomerular filtration rate: r = -0.21; P < .05), creatinine (r = 0.21;
P < .05), erythrocyte count (r = -0.24; P < .01), hemoglobin (r = -0.33; P <
.01), N-terminal pro-B-type natriuretic peptide (r = 0.25; P < .01), cholesterol
(r = -0.22; P < .05), LDL (r = -0.21; P < .05), New York Heart Association
functional class (r = 0.21; P < .05), hsCRP (r = 0.32; P < .01), IL-6 (r = 0.31;
P < .01), and VWF (r = 0.27; P < .01). In multifactorial analysis, the predictors
of endocan levels were cholesterol level, cystatin C, and IL-6, predicting 54% of
variability. CONCLUSIONS: Endocan concentration among heart transplant recipients
is potentially connected with endothelial damage caused by subclinical
inflammation resulting from hyperlipidemia.
PMID- 27496492
TI - Right Ventricular Function in Patients With Left Ventricular Assist Device
Support by Pulsatile Polvad MEV and Continuous-Flow Pumps Heartware and Heartmate
II.
AB - BACKGROUND: Left ventricular assist device (LVAD) support is increasingly used in
patients with heart failure. The right ventricle (RV) plays a main role in LVAD
support. Little is known about the effects of pulsatile Polvad MEV devices or
continuouseconds flow pumps on RV function. We compared hemodynamic parameters of
RV in patients after implantation of Polvad MEV (PM) and Heartware (HW) or
Heartmate II (HMII) LVADs. METHODS: Forty-four patients were retrospectively
reviewed after implantation of PM (group P; n = 24 [21 M, 3 F]) or HW or HMII
(group C; n = 20 [20 M, 0 F]) LVADs from April 2007 to February 2014. Hemodynamic
data-mean pulmonary pressure (mPAP), central venous pressure (CVP), cardiac
output (CO), and cardiac index (CI)-were collected before surgery, after surgery,
and every 2 hours in the intensive care unit, with the time points numbered from
1 to 120. Right ventricular work (RVW) was calculated according to the equation:
RCW = CO * (mPAP - CVP) * 0.0144 (g.m). RESULTS: Baseline characteristic of the
patients were similar. mPAP values were similar between groups. CVP values were
higher in group P, significantly at time points 5 and 7-33. CO values were higher
in group C, significantly from point 3 and almost all the time to point 43. CI
reached significance at point 9, 12-14, 16-19, and 30-41. RCW was higher in group
P before implantation. Post-implantation RCW values were higher in group C,
significantly at time points 19, 20, 32-34, 51-53, and 55-57. CONCLUSIONS:
Continuous-flow pumps more effectively optimize RV function than pulsatile LVADs,
which can result in more effective prevention of RV failure or insuffiency in
that group.
PMID- 27496493
TI - National Hematopoietic Stem Cells Transplant Registry in Poland: Nationwide
Internet Reporting System and Results.
AB - History of hematopoietic stem cell transplantations in Poland begins in early
1980s; the 1st bone marrow allotransplantation was performed in 1983 in the
Central Clinical Hospital of the Military Medical Academy in Warsaw. Following
years brought the 1st autologous stem cell transplantations. Ten years later,
unrelated bone marrow transplantation was performed for the 1st time by the team
of the Hematology and Blood and Marrow Transplantation Unit in Katowice. Since
then, hematopoietic stem cell transplantation developed to be standard procedure
and one of the most important therapies applied in leukemia treatment. The number
of allotransplantations in Poland has grown significantly in the past 2 decades,
which generated new needs and problems. In 2005, based on a new Transplant Law, a
National Transplants Registry was created. Its main role is to collect data
(registration of procedures and follow-up data) related to every transplantation
case for stem cells and tissues as well as for organs. We present statistics
concerning stem cell transplantations performed in Poland, as collected in the
National Transplants Registry in the years 2006-2014. There are 18 centers
transplanting hematopoietic stem cells in Poland. The total number of
hematopoietic stem cell transplantations performed in 2006-2014 was 3,537, with
allotransplantations from relatives accounted for 1,491 and from unrelated donors
for 2,046. The main indication for allotransplantation in past years was acute
leukemia.
PMID- 27496494
TI - Rhinosinusitis in Acute Leukemia Patients Undergoing Allogeneic Stem Cell
Transplantation-A Single-Center Experience.
AB - BACKGROUND: Although rhinosinusitis constitutes a major clinical problem in
general population, data on rhinosinusitis in patients undergoing allogeneic
hematopoietic stem cell transplantation (alloHSCT) are scarce. Therefore, the aim
of the study was to assess the frequency of rhinosinusitis, the impact of
rhinosinusitis on post-alloHSCT outcome, and to analyze risk factors potentially
predisposing to rhinosinusitis. METHODS: Retrospective analysis of acute leukemia
patients undergoing alloHSCT. RESULTS: A total of 87 patients (49 male), with a
median age of 36 years (range, 18-58), transplanted from 1999 to 2010, were
enrolled; 61 patients suffered from acute myeloid leukemia (AML) and 26 of acute
lymphoblastic leukemia (ALL). Fifteen patients (17.2%) experienced rhinosinusitis
before transplantation, among whom 5 (33%) experienced rhinosinusitis after
alloHSCT; 22 patients (25.3%), 12 AML and 10 ALL, experienced rhinosinusitis
after alloHSCT. The median time to rhinosinusitis was 200 days (range, 1-2,044).
11 patients experienced rhinosinusitis during the 1st 100 days after
transplantation, 8 during the 1st 30 days. Post-alloHSCT rhinosinusitis did not
affect overall survival of transplant patients (P = .35). In univariate analysis
only total body irradiation as part of conditioning (odds ratio [OR], 2.78; 95%
CI, 1-7.77) and previous nasal packing (OR, 5.18; 95% CI, 1.22-23.43) were
associated with higher incidence of rhinosinusitis. In multivariate analysis,
none of the analyzed parameters was shown to have an impact on rhinosinusitis
development. CONCLUSIONS: Rhinosinusitis is a frequent medical condition in
patients undergoing alloHSCT. The overall survival of patients developing
rhinosinusitis after HSCT is similar to survival of patients who do not. No risk
factors for developing rhinosinusitis could be identified.
PMID- 27496496
TI - Banking of Hematopoietic Stem Cells: Influence of Storage Time on Their Quality
Parameters.
AB - BACKGROUND: Banking of hematopoietic stem cells (HSCs) is a rapidly growing part
of the transplant field. The essence of the banking process is to maintain the
optimal quality parameters throughout the storage period, allowing successful
transplantation. METHODS: Our laboratory research was carried out on 126 HSC
samples that were collected by means of leukapheresis from patients with
lymphoproliferative diseases. The samples were frozen in a controlled rate and
stored up to 76 months in containers in vapor phase of liquid nitrogen. The
evaluation was performed after thawing the probes. Viability of nuclear cells was
assessed after incubation in Trypan blue, CD34+ phenotype cells were determined
by means of cytometry with the use of 7-aminoactinomycin D (7-AAD), and an
analysis of the proliferative potential of granulocyte-monocyte precursors was
performed. For comparative statistical analysis, the material was divided into 3
groups according to storage time: A: <1 month (n = 45); B: 1-12 months (n = 50);
C: >12 months (n = 31). RESULTS: In the examined groups, similar median values
were observed of nuclear cell viability (A, 86%; B, 87%; and C, 83%) and CD34+
cells (95%, 94.5%, and 95.8%, respectively). A gradual, nonsignificant, reduction
in the median of granulocyte-monocyte precursors was found: 68 * 10(4)/kg of body
weight (kg bw), 48.5 * 10(4)/kg bw, and 47 * 10(4)/kg bw, respectively.
Statistical analysis with the use of the Kruskal-Wallis test showed a P value of
>.05 for all variables. CONCLUSIONS: There were no significant differences in the
viability of nuclear cells, CD34+ cells, and proliferative potential granulocyte
monocyte precursors between groups. Storage for up to 76 months does not change
the essential quality parameters, and HSCs could be qualified for distribution.
PMID- 27496495
TI - Azacitidine Use After Allogeneic Stem Cell Transplantation-Results From the
Polish Adult Leukemia Group.
AB - BACKGROUND: Relapse of primary hematologic disease constitutes an important
reason for failure of allogeneic hematopoietic stem cell transplantation
(alloHSCT). There are very few treatment modalities for this indications.
Therefore, there is a need for novel effective therapies and even more for the
prevention of relapse. There are scarce data that azacitidine can be used for
these purposes. METHODS: At the Polish Adult Leukemia Group, we retrospectively
analyzed the results of azacitidine treatment after alloHSCT. Relapsing patients,
patients with minimal residual disease/mixed chimerism, and patients in complete
remission with high risk of relapse were analyzed separately. There were 17
patients, 6 with myelodysplastic syndrome, 11 with acute myeloid leukemia, 8
male, and overall median age of 56 years (range, 15-78); 7 patients received
donor lymphocyte infusion (DLI). RESULTS: Patients treated because of relapse
received a median of 3 (range, 1-6) cycles of azacitidine, patients receiving
preemptive treatment received a median of 4 cycles (range, 2-6), and those on
maintenance received a median of 5 cycles (range, 3-5). Toxicity was
considerable, especially in relapse-neutropenia (67%), anemia (67%),
thrombocytopenia (100%), serious infections (78%)-and preemptive settings. Median
overall survival of patients treated for relapse reached 6.8 months (95%
confidence interval [CI], 0.7-infinity), with better survival observed in
patients with temporary disease control (7.7 vs 4.7 mo) and without previous
exposure to azacitidine (7.7 vs 3.4 mo). One-year overall survival reached 75%
(95% CI, 13%-96%) for preemptive and 50% (95% CI, 0%-91%) for maintenance
treatment. DLI did not aggravate graft-versus-host disease. CONCLUSIONS:
Effectiveness of azacitidine in relapsing patients is disappointing. Azacitidine
seems to be promising in preemptive and maintenance settings. Toxicity is
considerable. Further research is needed.
PMID- 27496497
TI - Liquid Storage of Hematopoietic Stem Cells Versus Proliferative Potential Colony
Forming Unit Granulocyte-Monocytes: Validation of Cell Processing.
AB - BACKGROUND: The material for transplantation must be of the highest quality. As
far as we know, short-term storage is one of the crucial points of stem cell
banking. According to the quality assurance system in a stem cell bank, each step
of cell processing must be validated. The aim of this study was to assess the
influence of short-term storage conditions into a clonogenic assay. METHODS:
Material was collected from mobilized peripheral blood by means of leukapheresis
from 15 patients. Samples were stored at 4 degrees C and 20 degrees C; samples
were evaluated on the day of leukapheresis and after 24 hours and after 48 hours
of storage. The number of colony-forming unit granulocyte-monocyte (CFU-GM)
precursors was analyzed with the use of in vitro culture. The material was
evaluated before freezing and after thawing. RESULTS: The average number of CFU
GM precursors in the material stored at 4 degrees C before freezing on the day of
collection was 84/10(5) nuclear cells (nc) and after 24 hours and 48 hours of
storage was, respectively, 62/10(5) nc (P = .011719) and 36/10(5) nc (P =
.02088). The average of the CFU-GM precursors in material stored at 20 degrees C
after 24 hours and 48 hours of storage amounted to 33/10(5) nc (P = .004439) and
2/10(5) nc (P = .00346), respectively. CONCLUSIONS: In our study, the number of
colonies of CFU-GM after 24 hours and 48 hours of storage, both at 4 degrees C
and 20 degrees C, was significantly reduced compared with the number of colonies
on the day of collection. Significantly greater numbers of CFU-GM precursors were
observed in the material stored before freezing at 4 degrees C in comparison with
the material stored at 20 degrees C.
PMID- 27496498
TI - Autologous Hematopoietic Stem Cell Transplantation for Adults With Acute Myeloid
Leukemia.
AB - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) remains the most
efficacious therapy in patients with acute leukemia. For older patients and those
lacking a related HLA-compatible donor, autologous transplantation (auto-HSCT) is
a valid alternative therapeutic option. METHODS: From 1997 until 2014 in the
Department of Hematooncology and Bone Marrow Transplantation, Medical University
of Lublin, Poland, 29 auto-HSCT were performed in patients with acute myeloid
leukemia (AML; 15 men and 14 women; median age, 52.2 years). The following FAB
types of AML were diagnosed: M0, 3; M1, 4; M2, 6; M4, 10; and M5, 6. Patients
with AML were classified into 3 cytogenetic prognostic groups: high risk, 9;
intermediate risk, 16; and low risk, 4. Twenty-five were in first complete
remission and 4 in second complete remission. The peripheral HSCs mobilized after
chemotherapy (mainly second course of consolidation) and granulocyte colony
stimulating factor were the source of the stem cells in all cases. The median
number of infused CD34+ cells was 3.58 * 10(6)/kg. The conditioning regimen was
busulfan and cyclophosphamide in all patients with AML. The intravenous form of
busulfan was applied in the last 15 patients. RESULTS: The median time for
absolute neutrophil count recovery >0.5 * 10(9)/L and for platelet count >20.0 *
10(9)/L was 12 and 16.5 days, respectively. Treatment-related mortality rate in
the whole group was 3.4% (1 patient with sepsis in the aplastic period). The
median follow-up time of survivors was 21.9 months (range, 11.7-142.4). The 3
year projected disease-free survival and overall survival rates were 60% and 68%,
respectively. CONCLUSIONS: Our data confirm that auto-HSCT is a valuable
therapeutic option for patients with AML, especially older patients and those
lacking related HLA-compatible donors.
PMID- 27496499
TI - Changes in Technique and Indications for Keratoplasty in Poland, 1989 to 2014: An
Analysis of Corneal Transplantations Performed at Saint Barbara Hospital, Trauma
Center, Sosnowiec, Poland.
AB - BACKGROUND: The purpose of this work was to study the evolving trends in
techniques and indications for corneal transplantation in Poland. METHODS: This
retrospective, descriptive analysis of corneal transplantations was performed at
the Ophthalmology Department of Saint Barbara Hospital, Trauma Center, Sosnowiec,
Poland, between 1988 and 2014. Structure of indications and surgery type rates
over 26 years were tabulated by means of 5-year intervals. RESULTS: Between 1989
and 2014, 1762 corneal transplantations were performed, including 1375 (78%)
cases of penetrating keratoplasty, 137 (8%) lamellar keratoplasty, 112 (6%) patch
grafts, and 138 (8%) keratolimbal allografts. The major indications and their
respective overall percentage were corneal leucoma (24%), pseudophakic/aphakic
bullous keratopathy (22%), Fuchs dystrophy (13%), keratoconus (13%), re-graft
(11%), keratitis (9%), and limbal stem cell deficiency (8%), with changes in
relative frequency of the leading indications over the following time intervals.
The number of corneal transplantations gradually increased during the years
reviewed. The rates of lamellar, keratolimbal, and patch grafts have grown
dynamically since 2010, reaching 20%, 17%, and 12%, respectively, of procedures
performed during 2010 to 2014. CONCLUSIONS: Over the past quarter of a century,
there has been evolution in corneal transplantation service, from the first
penetrating keratoplasty to the wide spectrum of procedures, including
femtosecond laser-assisted keratoplasty. Although, since 2010, the rates of
lamellar and keratolimbal allografts have grown rapidly, penetrating keratoplasty
has remained the leading technique.
PMID- 27496500
TI - Effect of Recombinant Human Prolactin Addition to Biolasol Solution on
Biochemical Indicators in Perfundates of Porcine Kidneys.
AB - BACKGROUND: The influence of recombinant human prolactin (rh-PRL) added to
Biolasol solution (concentration 1 MUg/L) on selected markers (pH, osmolarity,
Na(I) and K(I) concentration) and enzymatic activity (alanine aminotransferase
[ALT], aspartate aminotransferase [AST], and lactate dehydrogenase [LDH]) in
perfundates was investigated during flushing and preservation of the isolated
porcine kidneys. METHODS: The pH, osmolarity, concentration of K(I) and Na(I),
and enzymatic activity were determined in perfundates collected after the 5th and
30th minutes of perfusion, after 24 hours of organ preservation, and in the 5th
and 30th minutes of reperfusion. Kidneys had been flushed and stored in Biolasol
(control group) and in Biolasol with rh-PRL (experimental group). Obtained
results were compared with Biolasol solution. RESULTS: In the experimental group,
the decrease in pH value in the 5th minute of reperfusion was noted. There was an
increase in K(I) concentration, and Na(I) concentration decreased in the 5th and
30th minutes of reperfusion. ALT activity during perfusion and preservation
increased, whereas at the 5th and 30th minutes of reperfusion it decreased. AST
activity increased during perfusion and preservation and decreased in the 5th and
30th minutes of reperfusion. LDH activity was increased but decreased in the 5th
minute of reperfusion. CONCLUSIONS: Addition of 1 MUg/L rh-PRL to Biolasol
solution decreases pH and osmolarity values; influences Na(I) and K(I)
concentration; increases ALT, AST activity during perfusion and preservation of
organs; and decreases ALT, AST activity during reperfusion.
PMID- 27496501
TI - Caspase-3 Expression and ALT, AST, and GGT Activity After 24 Hours of Porcine
Liver Cold Storage, Depending on the Type of Transgenesis.
AB - BACKGROUND: Because of an insufficient number of human organs for
transplantation, xenotransplantation may become an effective alternative. We
aimed to analyze if the type of transgenesis has an influence on the hepatic
caspase-3 expression, the enzyme that executes apoptosis as well as ALT, AST, and
GGT activity after 24 hours of cold storage. METHODS: The experiment was carried
out on the 24 livers of Polish White Landrace pigs carrying human alpha1,2
fucosyltransferase and/or alpha-galactosidase (GAL) genes and livers without this
genetic modification (control). Livers were perfused, stored for 24 hours in
solution, and subsequently re-flushed. Hepatic concentration of the caspase-3
protein and its mRNA expression were measured just after the animal was killed as
well as after 30 minutes of perfusion and after 24 hours of cold storage followed
by 30 minutes of reperfusion. Caspase-3 mRNA level was detected with the RT-PCR
method. Protein concentration (capsase-3 active and inactive) was assessed with
the Western blotting technique. Kinetic methods were applied for the analysis of
the ALT, AST, and GGT activity. RESULTS: The highest increase of the ALT activity
after cold storage was observed in the group with GAL transgenesis, whereas the
GGT activity was highest in the unmodified livers. There was no difference in the
caspase-3 expression and AST activity after cold storage as compared with the
respective initial results (P = .57 and P = .97, respectively). CONCLUSIONS: It
appears that transgenesis does not aggravate ischemic injury of the liver.
PMID- 27496502
TI - Endothelial Nitric Oxide Synthase and Endothelin-1 Expression in the Early Post
Porcine Kidney Autotransplantation Period.
AB - BACKGROUND: The aim of this study was the assessment of endothelial nitric oxide
synthase (eNOS) and endothelin-1 (EDN-1) expression in porcine kidneys on the
14th and 30th days after the autotransplantation procedure. METHODS: The research
was conducted on 12 animals that underwent a left renal transplantation procedure
with further standardized rinsing and 24-hour storage in 4 degrees C;
subsequently, the kidneys were implanted in the right retroperitoneal space after
right-sided nephrectomy. Removed kidneys were examined (group 0). Six randomly
chosen animals (group 1) were under observation for 14 days and 6 others (group
2) for 30 days. RESULTS: After these observation periods, euthanasia was
performed on the animals and 4-g samples were collected from the renal cortex and
medulla. The Western blot technique was used to detect the eNOS and EDN-1
expression at the protein level. The obtained results are presented as absolute
values of integrated optical density. Stable graft function was observed in all
animals from the 2nd day after the procedure. eNOS in group 1 reached the mean
value of 1.064 and was statistically significantly lower than in group 2 (2.085)
or in the control group 0 (3.318). In the case of EDN-1 expression on 14th day
after transplantation, the medium level was reported (0.248), which was similar
to group 0 (0.216), whereas group 2 presented values 2 times higher (0.743).
CONCLUSIONS: A lowered eNOS level in the organ was observed on the 14th day after
autotransplantation of a pig kidney; further enzyme normalization is associated
with increased EDN-1 expression.
PMID- 27496503
TI - Determination of Concentrations of Azathioprine Metabolites 6-Thioguanine and 6
Methylmercaptopurine in Whole Blood With the Use of Liquid Chromatography
Combined With Mass Spectrometry.
AB - BACKGROUND: 6-Mercaptopurine (6-MP) and its prodrug azathioprine (AZA) are used
in many autoimmune diseases and after solid-organ transplantation. Their
properties are mediated by active metabolites, 6-thioguanine nucleotides (6-TGN),
and 6-methylmercaptopurine (6-MMP). The most common adverse effects are myelo-
and hepato-toxicity. The aim of the study was quantification of 6-TG and 6-MMP,
with the use of liquid chromatography combined with tandem mass spectrometry
(LC/MS/MS) in solid-organ transplant recipients. METHODS: In 33 patients, kidney
transplant recipient (n = 25) and liver transplant recipient (n = 8) intra
erythrocyte concentrations of 6-TG and 6-MMP were measured with the use of
LC/MS/MS. RESULTS: The mean concentration of 6-TG was 205.35 +/- 157.62 pmol/8 *
10(8) red blood cells (RBC); median concentration of 6-MMP was 1064.1 (35.78
11,552.9) pmol/8 * 10(8) RBC. There were no correlations between 6-TG levels and
peripheral blood parameters (white blood cell count, WBC; hemoglobin, Hb
concentration; PLT, blood platelet count) or alanine aminotransferase activity
(AlAT) activity. Relationships between 6-MMP concentrations and peripheral blood
parameters (WBC, Hb, PLT) or AlAT activity have not been found. Subgroups with
leukopenia, anemia, thrombocytopenia, and liver dysfunction did not differ in
concentrations of 6-TG or 6-MMP. We have observed a negative correlation between
daily azathioprine dose and WBC count (r = -0.37, P = .04). CONCLUSIONS:
Relationships between concentrations of azathioprine metabolites and
myelotoxicity or hepatotoxicity have not been confirmed. Further studies on
larger groups of patients would be helpful in a more accurate understanding of
the impact of azathioprine metabolites on parameters of bone marrow and liver
function.
PMID- 27496504
TI - Concentration of Tumor Necrosis Factor-alpha and Interleukin-1beta in Isolated
Porcine Liver Depending on Type of Transgenesis.
AB - BACKGROUND: Transgenic animals may serve as organ donors in human organ
transplantation. However, the number of the studies addressing all doubts related
to this issue is currently insufficient for the clinical application of this
approach. The aim of this study was to analyze the hepatic tumor necrosis factor
alpha (TNF-alpha) and interleukin-1beta (IL-1beta) synthesis during a 24-hour
cold preservation of the transgenic pig liver, depending on the type of
transgenesis. MATERIALS AND METHODS: The study was carried out on wild-type and
transgenic pig livers with transferred human alpha1,2-fucosyltransferase (FUT)
and/or alpha-galactosidase (GAL) gene (four groups; n = 6). Harvested livers were
perfused for 30 minutes and stored for 24 hours in Biolasol (Biochefa) solution
at 4 degrees C with a subsequent 30-minute reperfusion (reflush). TNF-alpha and
IL-1beta concentrations were analyzed with an enzyme-linked immunosorbent assay.
Perfusates were collected during the initial perfusion as well as after 24 hours
of preservation and during the reperfusion. Tissue samples were harvested just
after animal sacrifice, and after organ perfusion and reperfusion. RESULTS: A
decrease in TNF-alpha concentration in homogenates was noted after both perfusion
and reperfusion in all experimental groups. In contrast, there was a significant
decrease in IL-1beta concentration in the group with combined human FUT and GAL
transgenes. Concurrently, increases in TNF-alpha and IL-1beta concentrations were
observed in the reperfusion perfusates in all groups. CONCLUSION: This study
shows that IL-1beta is synthesized in the ischemic livers of the transgenic
animals with both human alpha1,2-fucosyltransferase and alpha-galactosidase
transgenes. Further analysis is required to determine the importance of this
observation.
PMID- 27496505
TI - Kaposi Sarcoma in the Genital Area in a Kidney Transplant Patient: A Case Report
and Literature Review.
AB - BACKGROUND: Kaposi sarcoma (KS) is a cancer with an incidence in patients after
transplantation (Tx) that is 500 times greater than that in the healthy
population. The risk of KS increases significantly during therapy, especially
when immunosuppressive therapy with cyclosporine A (CsA) is used. Most cases of
KS develop during the first 2 years after transplantation. After a KS diagnosis,
it is recommended to reduce the doses of immunosuppressive medications.
Conversion of immunosuppressive treatment into mammalian target of rapamycin (m
TOR) inhibitors is strongly suggested. PATIENTS AND METHODS: We present the case
of a 65-year-old man with end-stage renal disease (ESRD) of unknown etiology, who
had kidney transplantation in 2008. Immunosuppressive protocol was based on CsA,
mycophenolate mofetil (MMF) and prednisolone (PRE). In 2011, during the
dermatological consultation, on the penis glans a purple stain of uneven surface
was noted. Histology study revealed the presence of KS. The treatment was
modified. The patient was converted from CsA to everolimus. Before converting,
the creatinine concentration was 1.79 mg/dl and proteinuria less than 0.3 g/day.
RESULTS: The change in the scheme of immunosuppresion from CsA to everolimus was
performed to treat the Kaposi sarcoma. Gradually, within a year, the KS was
cured. However, the graft function deteriorated, and the graft was lost in one
years' time. CONCLUSION: We present the first documented case of KS in the
genital area of a kidney patient. The reduction in the strength of
immunosuppression, and the introduction of an m-TOR inhibitor, may have
contributed to the deterioration of kidney function, however it was substantial
in the treatment of KS.
PMID- 27496506
TI - Renal Tumor in Allogeneic Kidney Transplant Recipient.
AB - BACKGROUND: Malignancies will be a leading cause of mortality in renal transplant
recipients in the next 20 years. Renal cell cancer (RCC) is the most common
urologic cancer in kidney transplant recipients. The risk of RCC development in
kidney transplant recipients is 15-100 times higher than in the general
population. The purpose of the current retrospective study was to assess the
frequency of nephrectomies performed because of renal tumors in the native
kidneys in kidney transplant recipients in the Department of General and
Transplantation Surgery at the Medical University of Warsaw between 2010 and 2014
year; the identification of kidney recipients diagnosed with RCC; and
epidemiologic, clinical, and histopathological aspects associated with RCC.
PATIENTS AND METHODS: A total of 319 nephrectomies were performed in the
Department of General and Transplantation Surgery at the Medical University of
Warsaw between 2010 and 2014 year. Renal tumors were diagnosed in 25 renal
transplant recipients. RESULTS: Among malignant tumors, 13 cases of RCC and 1
case of post-transplant lymphoproliferative disorder (PTLD) were observed. There
was no significant difference between age and duration of pretransplantation
dialysis in patients with RCC and patients with benign tumors (P = .14 and P =
.91, respectively). Body mass index was significantly higher in patients with RCC
than in patients with benign tumors (P = .04). CONCLUSIONS: Renal cell cancer is
more common among male kidney recipients. There is a good Polish screening system
allowing detection of kidney cancer in native kidney. We recommend performing
periodic screening for kidney cancers to obtain an early diagnosis.
PMID- 27496507
TI - Delayed, Uncommon Recurrence of Hepatocellular Carcinoma After Liver
Transplantation: A Case Report.
AB - We report a case of a 27-year-old man diagnosed with the infection of HBV delta
in the 8th month of life. The treatment complied with evidence-based medical
guidelines, comprising neoadiuvant chemotherapy and surgery. Liver
transplantation from a deceased donor followed by chemotherapy was performed when
the patient was 16 years 9 months of age because of recurrent HCC tumor. The
patient qualified for immunosuppressive treatment (rapamycin, tacrolimus),
lamivudine, anti-HBs globulin intravascular infusion, and anti-HBV vaccination as
a prophylaxis against reinfection with HBV. In conclusion, this case demonstrates
the importance of a postoperative follow-up of patients with HCC, even years
after liver transplantation.
PMID- 27496508
TI - Renal Artery Denervation in Patient After Heart and Kidney Transplantation With
Refractory Hypertension.
AB - We describe the case of a 54-year-old patient after renal and heart
transplantation in whom uncontrolled hypertension was diagnosed. Despite combined
antihypertensive therapy, no significant therapeutic effect was achieved.
Clinical assessment of ambulatory blood pressure monitoring (ABPM) revealed the
ineffectiveness of a bisoprolol, nitrendypin, klonidyn, ramipryl, furosemide, and
doxasosine combination used at high doses. High blood pressure levels with their
effect on a hypertrophic transplanted heart (left ventricular mass 254 g) and
poor renal graft function (39 mL/kg/min) posed an extremely high risk of future
cardiovascular complications, and were the reason to perform a native renal
arteries denervation. The procedure was carried out through the right femoral
artery with the use of a 6F guiding catheter. During a 1-year observation,
significant decreases in ABPM systolic and diastolic blood pressures were
observed after the procedure (168/88 mm Hg vs 154/77 mm Hg, respectively).
Moreover a significant regression of left ventricular mass (215 g/m(2)) and
stable renal graft function were noted. The presented case shows that native
renal arteries denervation may be successful and safe in kidney and heart
transplant recipients. Moreover, during the 1-year follow-up, the reduction in
blood pressure was followed by a reduction in transplanted heart hypertrophy,
both leading to regression of cardiovascular risk for the patient.
PMID- 27496509
TI - Erratum.
PMID- 27496510
TI - Erratum.
PMID- 27496511
TI - Evaluation of Pastorex meningitis kit performance for the rapid identification of
Neisseria meningitidis serogroup C in Nigeria.
AB - BACKGROUND: Neisseria meningitidis serogroup C (NmC) has caused outbreaks in
Nigeria of increasing size in three consecutive years since 2013. Rapid
diagnostic tests (RDTs) for meningitis can facilitate quick identification of the
causative pathogen; Pastorex can detect N. meningitidis serogroups A, C (NmC),
Y/W135, N. meningitidis serogroup B/Escherichia coli K1, Haemophilus influenzae
type b (Hib), Streptococcus pneumoniae, and group B Streptococcus. There is no
published field evaluation of Pastorex in the identification of NmC. We report
our experience with Pastorex in detecting NmC in field conditions. METHODS:
During sequential outbreaks of NmC in Nigeria in 2013, 2014 and 2015,
cerebrospinal fluid (CSF) was collected from suspected cases of meningitis that
met the case definition. Pastorex latex agglutination rapid test was done in the
field and trans-isolate media were inoculated with CSF for culture and/or PCR,
which was used as the reference standard for 63 paired samples. RESULTS: The
sensitivity of Pastorex for NmC was 80.0% (95% CI 65.4-90.4%) and the specificity
was 94.4% (95% CI 72.7-99.9%). The positive likelihood ratio (LR) was 14.4 (95%
CI 2.1-97.3) and negative LR was 0.2 (95% CI 0.1-0.4). The positive and negative
predictive values (PPV and NPV) were 97.3% (95% CI 85.8-99.9) and 65.4% (95% CI
44.3-82.8), respectively, with a prevalence estimate of 71.4% (95% CI 58.6-82.1).
CONCLUSION: Pastorex showed good performance in detecting NmC under field
conditions. Prepositioning Pastorex at peripheral health facilities during non
epidemic periods is constrained by a short shelf-life of 1 month after the kit is
opened. There is need for development of RDTs that are cheaper and with less
challenging requirements for storage and usage.
PMID- 27496512
TI - The impact of a rural sanitation programme on safe disposal of child faeces: a
cluster randomised trial in Odisha, India.
AB - BACKGROUND: Unsafe disposal of child faeces is persistent and may lead to
considerable impact on the health of young children. Research is limited on the
impact of sanitation or hygiene interventions to improve child faeces disposal
practices. METHODS: In the context of a randomised controlled trial to assess the
health impact of a programme in Odisha, India, to promote rural sanitation under
the Government of India's Total Sanitation Campaign, we explored whether the
intervention affected the safe disposal of faeces of children under-5 years of
age. RESULTS: At baseline, 1.1% of households practised 'safe' disposal of child
faeces, either disposing it in a toilet or by burial. The intervention increased
safe disposal of child faeces to 10.4% in intervention households, compared to
3.1% in the control households (RR 3.34; 95% CI 1.99-5.59). This increase in safe
disposal is attributable to increases in latrine presence in the intervention
communities; the intervention did not change safe disposal practices above and
beyond the increase in latrine coverage. CONCLUSIONS: The very modest increase in
safe disposal, while statistically significant, is not likely to have
consequential health benefit. To achieve open defecation free communities,
sanitation interventions will need to develop behaviour change approaches to
explicitly target safe disposal behaviours.
PMID- 27496513
TI - Can we replace HIV sentinel surveillance platform with prevention of parent-to
child transmission (PPTCT) program data to assess HIV burden and trends in India?
AB - BACKGROUND: Estimates of HIV burden in India are based on HIV sentinel
surveillance (HSS), which has limitations such as insufficient sample size for
district level analysis and ethical concerns. We analysed prevention of parent-to
child transmission (PPTCT) program data, for its suitability for HIV surveillance
in India. METHODS: Correlation and differences in ante-natal clinic (ANC)
attendees' HIV prevalence from the last four rounds of HSS (2007-2012) and PPTCT
data for the corresponding years were analysed at national, state and district
levels. Sensitivity and region wise analysis were also done. RESULTS: The PPTCT
program covered a higher number of districts and ANC attendees than HSS.
Correlation of HIV prevalence from PPTCT data with HSS was high (0.99) at
national level, moderate (0.66-0.86) at state level, and low (0.43-0.62) at
district level. HIV prevalence levels from HSS were generally higher than those
from PPTCT data. As the coverage of PPTCT program and HSS improved, the
differences between HIV prevalence from these two data sources increased.
Sensitivity analysis showed significant differences in ANC attendees' HIV
prevalence from HSS and PPTCT, even among districts with high HIV test uptake
level in PPTCT program. CONCLUSIONS: PPTCT program data can be utilised for HIV
surveillance in India as it has better coverage and will avoid ethical issues and
expenditures related to HSS.
PMID- 27496514
TI - Evaluating the efficacy of a centrifugation-flotation method for extracting
Ascaris ova from soil.
AB - BACKGROUND: Soil transmitted helminths (STH) continue to be associated with high
burdens of disease, with an estimated 1.45 billion people infected with STH
globally. The promotion and construction of latrines is considered the first
barrier to prevent transmission of STH. The absence of a reliable method to
extract STH ova from soil makes it challenging to examine whether the use of
latrines may or may not have an effect on environmental contamination with ova.
The present study evaluated the recovery rate of a method developed to extract
STH ova from soil. METHODS: The adapted centrifugation and flotation technique
was applied to 15 soil types, which were seeded with Ascaris suum ova. Soil type,
soil moisture content, soil texture and organic matter content were assessed for
each soil sample. RESULTS: The average ova recovery rate was 28.2%, with the
recovery rate of the method decreasing with increasing soil moisture content,
particle size and organic matter content. The association between recovery rate
and organic matter content was statistically significant. CONCLUSIONS: The
present study identified a low recovery rate for an adapted centrifugation
flotation method, although this was similar to the recovery rate demonstrated by
other methods developed for soil. Soil organic matter content was significantly
associated with ova recovery rates.
PMID- 27496515
TI - Natural transovarial and transstadial transmission of Leishmania infantum by
naive Rhipicephalus sanguineus ticks blood feeding on an endemically infected dog
in Shiraz, south of Iran.
AB - BACKGROUND: The visceral leishmaniasis parasite, Leishmania infantum, is
naturally transmitted through the bites of phlebotomine sand flies. Alternative
routes of transmission are questioned. The main aim is to verify the passage of
L. infantum kDNA in ticks, Rhipicephalus sanguineus, blood feeding on a
parasitemic dog in Shiraz, south of Iran. METHODS: A total of 180 Leishmania-free
ticks collected from fields and bred on lab rodents, were divided into eight
groups and allowed to feed on a dog (Canis familiaris) for fixed periods of time.
These and all third generation stages of ticks were checked for L. infantum kDNA
using conventional PCR protocol. RESULTS: The infection rate was significantly
higher in female than male ticks (p=0.043). The rates were higher among nymphs
(25/60; 42%) than adult ticks (37/120; 30.8%). The kDNA of L. infantum was not
detected in ticks 24 h post-feeding. It was, however, positive among the second
to fourth groups of nymphs (4/10; 40%, 10/20; 50% and 11/20; 55%) and adult
(12/30; 40%, 14/30; 46.6% and 11/30; 36.6%) ticks. Eggs and unfed larvae
recovered from the third and fourth adult groups (2 weeks, 4 weeks) were 100% PCR
positive. The data revealed the passage of L. infantum kDNA in nymphs and adults
of brown dog tick following fixed time intervals post blood feeding on an
infected dog. CONCLUSIONS: The natural transovarial and transstadial passage of
kDNA through ticks was shown by PCR.
PMID- 27496516
TI - Characterization of enteropathogenic Escherichia coli of clinical origin from the
pediatric population in Pakistan.
AB - BACKGROUND: Enteropathogenic Escherichia coli (EPEC) is one of the leading causes
of watery diarrhea among children. METHODS: In this study EPEC isolates from the
pediatric population of Pakistan (2010-2012) were subjected to phylotyping,
antibiotic susceptibility, extended-spectrum beta-lactamase (ESBL) profiling and
evaluation of one representative strain from each panel of phylotypesin Galleria
mellonella, infection model. RESULTS: A total of 46/225 (20.4%) stool samples
were positive for EPEC. Isolates mainly belong to D phylogroup (18, 39%) followed
by nontypeable (10, 22%), B1 (9, 20%), B2 (8, 17%) and A (1, 2%). High resistance
was observed for ampicillin (42, 91%), erythromycin (41, 89%), cefaclor (37,
80%), trimethoprim/sulfamethoxazole (36, 78%), tetracycline (36, 78%). Among
nalidixic acid resistant isolates 13 (28%) showed presence of single nucleotide
polymorphism (SNP) in parC (C330-T330) whereas 1 (2%) isolate showed gyrB (A660
T660) SNP. Furthermore, 27 (59%) isolates were ESBL producers. Representative
isolates of phlyotypes A and B2 showed enhance killing of G. mellonella compared
to ones belonging to phylotypes B1 and D. CONCLUSIONS: Non-typeable EPEC strains
were frequently observed. ESBL production in ESBL producers was found to be
plasmid mediated. No significant association of antibiotic resistance profile
with specific phylogroup of EPEC was found, however G. mellonella infection model
differentiated representative phylotypes.
PMID- 27496517
TI - B1c genetic subtype of coxsackievirus A16 associated with hand, foot and mouth
disease in Andaman Islands, India.
AB - BACKGROUND: An outbreak of hand, foot and mouth disease (HFMD) occurred in the
Andaman Islands in 2013. Therefore, we aimed to identify the aetiological agent
and to explore its genetic characteristics. METHODS: Clinical specimens were
subjected to virus isolation, further confirmed by sequencing the partial VP1/2A
region of enterovirus, and analysed using MEGA 6 software with intra-serotype
reference sequences. RESULTS: Coxsackievirus A16 (CV A16) was found to be the
causative agent, closely grouped with B1c genetic clusters of CV A16. However, it
has significant genetic distance (K2P=0.059%) with B1c sub-clusters. CONCLUSION:
Extended research work should be carried out to better understand the emerging
nature of CV A16 associated with HFMD in these islands.GenBank accession numbers:
KU523376-KU523387.
PMID- 27496518
TI - Schistosomiasis and soil-transmitted helminth infections in schoolchildren in
north-eastern Democratic Republic of the Congo.
AB - BACKGROUND: There is a paucity of epidemiological data pertaining to
schistosomiasis and soil-transmitted helminth (STH) infections in the Democratic
Republic of the Congo (DRC). METHODS: A cross-sectional survey was carried out in
the north-eastern part of DRC enrolling 400 schoolchildren aged 9-14 years. Stool
and urine samples were subjected to standard diagnostic methods and examined
under a microscope for helminth eggs. RESULTS: Four out of five children were
infected with at least one helminth species. Schistosoma mansoni was the
predominant species (57.8%). Urine examinations were all negative for S.
haematobium. CONCLUSIONS: S. mansoni and STH infections are highly endemic in the
surveyed part of the DRC, calling for interventions in school-aged children.
PMID- 27496519
TI - Remimazolam: Pharmacologic Considerations and Clinical Role in Anesthesiology.
AB - Midazolam, fentanyl, and propofol are commonly used for sedation in modern
anesthesia practice. These agents possess characteristics that have afforded
various anesthetics to be delivered and produce relatively safe and effective
outcomes. However, each agent has certain drawbacks in clinical practice.
Remimazolam, a novel benzodiazepine created out of so-called soft drug
development, is an ultrashort-acting intravenous sedative-hypnotic currently
being investigated in clinical trials. In this review, we evaluate the recent
literature on the use of remimazolam in clinical practice as compared with
current sedative agents, and we describe its potential roles for use in sedation.
A literature search of the Medline database (2012-May 2016) was performed.
Additional references were identified from a review of literature citations,
manufacturer reports, and professional meeting abstracts. All premarket studies
involving remimazolam as the primary study drug were evaluated. Literature
describing the pharmacokinetics and pharmacodynamics of remimazolam, propofol,
and midazolam was also included. Phase I and II studies in the United States have
shown remimazolam to be a safe and effective option for procedural sedation.
Unlike midazolam and propofol, remimazolam undergoes organ-independent metabolism
to an inactive metabolite. Because remimazolam follows first-order
pharmacokinetics, prolonged infusions or higher doses are unlikely to result in
accumulation and extended effect, making it favorable for use as an intravenous
anesthetic and for sedation in the intensive care unit. It is expected that phase
III trials will further describe the niche that remimazolam may be able to occupy
in clinical practice. Postmarket cost-benefit analyses will need to be performed.
PMID- 27496521
TI - Hastened death in ALS: Damaged brains and bad decisions?
PMID- 27496520
TI - Cognitive impairment, behavioral impairment, depression, and wish to die in an
ALS cohort.
AB - OBJECTIVE: To evaluate relationships among cognitive, behavioral, and
psychiatric/psychosocial measures assessed in a multicenter cohort of patients
with amyotrophic lateral sclerosis (ALS). METHODS: Recently diagnosed patients
with definite or probable ALS diagnosis were administered 7 standardized
psychiatric/psychosocial measures, including the Patient Health Questionnaire for
diagnosis of depression and elicitation of wish to die. The Cognitive Behavioral
Screen was used to classify both cognitive and behavioral impairment (emotional
interpersonal function). An ALS version of the Frontal Behavioral Inventory and
Mini-Mental State Examination were also administered. RESULTS: Of 247 patients
included, 79 patients (32%) had neither cognitive nor behavioral impairment, 100
(40%) had cognitive impairment, 23 (9%) had behavioral impairment, and 45 (18%)
had comorbid cognitive and behavioral decline. Cognitive impairment, when
present, was in the mild range for 90% and severe for 10%. Thirty-one patients
(12%) had a major or minor depressive disorder (DSM-IV criteria). Cognitive
impairment was unrelated to all psychiatric/psychosocial measures. In contrast,
patients with behavioral impairment reported more depressive symptoms, greater
hopelessness, negative mood, and more negative feedback from spouse or caregiver.
A wish to die was unrelated to either cognitive or behavioral impairment.
CONCLUSIONS: While we found no association between cognitive impairment and
depression or any measure of distress, behavioral impairment was strongly
associated with depressive symptoms and diagnoses although seldom addressed by
clinicians. Thoughts about ending life were unrelated to either cognitive or
behavioral changes, a finding useful to consider in the context of policy debate
about physician-assisted death.
PMID- 27496522
TI - Oral NSAIDs versus other oral analgesic agents for acute soft tissue injury.
PMID- 27496523
TI - Photodynamic therapy-triggered bullous pemphigoid.
PMID- 27496524
TI - Characterization of clinically important dermatophytes in North of Iran using PCR
RFLP on ITS region.
AB - OBJECTIVE: Dermatophytosis is considered as one of the major public health
problems in the world. Accurate identification of the dermatophytes species is
important for recognition of the environment and animal sources of infection. In
this survey, 1500 clinical specimens taken from outpatients suspected of
dermatophytosis and they were examined by direct microscopy and culture.
MATERIALS AND METHODS: In total, three hundred and twelve dermatophytes were
isolates recovered in culture, they were identified using polymerase chain
reaction-restriction fragment length polymorphism (PCR-RFLP) method based on the
ribosomal DNA internal transcribed spacer (ITS) regions. RESULTS: Tinea pedis was
the most common clinical form (32.1%) followed by tinea cruris (24.4%), tinea
manuum (16.4%), tinea unguium (8.3%), tinea corporis (7.3%), tinea faciei (6.4%),
and tinea capitis (5.1%). Trichophyton interdigitale was the most frequent
isolate (38.2%), followed by Trichophyton rubrum (29.8%), Epidermophyton
floccosum (16.6%), Trichophyton tonsurans (14.8%) and Microsporum canis (0.6%).
The frequency of dermatophytosis was higher in males than in females and in the
age-group of 21-30 years. CONCLUSION: Our finding indicated that the incidence of
dermatophytosis caused by anthropophilic dermatophytes in Mazandaran province is
increasing. Also, this study provides valuable data for the prevention and
control of dermatophytosis in the southern coast of the Caspian Sea.
PMID- 27496525
TI - Fecal microbial transplantation in a pediatric case of recurrent Clostridium
difficile infection and specific antibody deficiency.
PMID- 27496526
TI - A comparison of autologous transplantation of retinal pigment epithelium (RPE)
monolayer sheet graft with RPE-Bruch's membrane complex graft in neovascular age
related macular degeneration.
AB - PURPOSE: To compare the outcome after choroidal neovascular (CNV) membrane
excision and retinal pigment epithelium (RPE) transplantation and make further
evaluation of two types of RPE grafts on the visual function in patients with
neovascular age-related macular degeneration (AMD), complicated by massive
subretinal haemorrhage. METHODS: We retrospectively reviewed 80 patients who
underwent CNV membrane excision with or without RPE transplantation. Two types of
RPE grafts were adopted, RPE-Bruch's membrane complex graft (subgroup 1) and RPE
monolayer sheet graft (subgroup 2). Outcome measures included pre- and
postoperative visual acuity score (VAS), clinical findings, complications and
recurrence rates. RESULTS: The mean VAS [Early Treatment of Diabetic Retinopathy
Study (ETDRS)] in the CNV membrane excision group was 11.06 +/- 18.28 at baseline
and 14.41 +/- 16.86 at follow-up (p = 0.12) in a mean follow-up period of 24.35
+/- 9.31 months. While in subgroup 1, VAS increased from 22.62 +/- 23.72 to 35.50
+/- 24.46 (p = 0.02) in a mean period of 20.63 +/- 6.25 months. The percentage of
visual acuity (VA) improvement (at least two or more lines changed) in subgroup 1
is 62.5%, which is significantly higher than that in CNV excision group (23.5%),
p = 0.02. In subgroup 2, VAS increased from 16.61 +/- 27.98 to 29.16 +/- 23.80 (p
= 0.02) in a mean period of 21.72 +/- 11.09 months. The percentage of VA
improvement in subgroup 2 is 58.0%, which is also significantly higher than that
in CNV excision group (23.5%), p = 0.02. Postoperative VA elevation was
comparable between the two subgroups (p = 0.05). Complications including retinal
detachment, proliferative vitreal retinopathy and CNV recurrence occurred in both
techniques. Central fixation stability was observed in eight eyes in subgroup 1
and five eyes in subgroup 2. CONCLUSIONS: The autologous RPE transplantation can
increase the vision of patients with haemorrhagic AMD. Two types of autologous
RPE grafts were both effective and comparable in restoring visual function and
central fixation stability.
PMID- 27496527
TI - Correlation of retinopathy with leukoaraiosis in patients with anterior
circulation infarcts.
AB - Although retinal and cerebral microvessels share similar embryological,
anatomical and physiological characteristics, the correlation between retinopathy
and leukoaraiosis (LA), a type of brain microvascular disease, is unclear. In the
present study, the sample included 213 patients admitted to the department of
neurology from January 2012 through October 2012. MRI and retinal photography
were performed within 48hours of hospitalization, and patient demographics,
comorbidities, preadmission medications and laboratory data were collected. MRI
images were used to divide the patients into LA and non-LA groups. Using
multivariate binary logistic regression, the effects of retinopathy on LA were
investigated. Of the 213 patients enrolled, 168 were included in this study (LA,
n=108; non-LA, n=60). Hypertension, coronary heart disease and carotid artery
plaque were more common in the LA group, and these patients showed higher blood
levels of C-reactive protein, homocysteine and triglycerides. The incidence of
retinopathy was significantly increased in the LA group compared with the non-LA
group, and there was a significant correlation between the severity of LA and
incidence of retinopathy. Retinopathy is an independent risk factor for LA and
can significantly increase the risk of LA when combined with age, coronary heart
disease, C-reactive protein, carotid artery plaque or systolic pressure. Taken
together, retinopathy is associated with LA in patients with anterior circulation
infarcts. Retinopathy is an independent risk factor for LA and an increase the
risk of LA, and thus facilitating the evaluation of LA.
PMID- 27496528
TI - Pineal region schwannoma arising from the trochlear nerve.
AB - Schwannomas arising from the trochlear nerve are very rare and to our knowledge,
less than 35 histologically documented cases have been reported in the
literature. There are no reports of a schwannoma in the pineal region. We report
a 24-year-old woman who underwent a para-occipital trans-tentorial approach and
gross total excision of a pineal region schwannoma arising from the trochlear
nerve. This is the first such reported case.
PMID- 27496529
TI - New frontiers in venous sinus stenting: Illustrative cases.
AB - Idiopathic intracranial hypertension (IIH) occurs rarely, with severe patients
recalcitrant to pharmacologic management often requiring cerebrospinal fluid
diversion. We report two patients with variant IIH successfully treated with
venous sinus stenting: 1) A 65-year-old man with severe vision loss, papilledema,
and cognitive decline treated with four telescoped stents across a long, severely
stenotic transverse-sigmoid system, and 2) a 58-year-old woman with headaches,
vision loss, and papilledema secondary to a jugular paraganglioma causing severe
jugular bulb stenosis that required contralateral venous sinus stenting. At 3
month and 1-month follow-up, respectively, ophthalmologic examinations showed
vision improvement. The first patient also had improved cognition, and the second
patient also had improved headaches.
PMID- 27496530
TI - Effectiveness of ovarian age as the background risk for aneuploidy screening in
an unselected pregnant population.
AB - The aim of this study was to assess the performance of first-trimester combined
screening when replacing the chronological maternal age by Anti-Mullerian hormone
(AMH) and antral follicle count (AFC)-derived ovarian ages, as the background
risk in trisomy risk estimation. A total of 639 pregnant women who completed
first-trimester combined screening together with AMH and AFC determination were
included. Trisomy risks were estimated based on three distinct 'maternal ages' as
a-priori risk (chronological age, AMH- and AFC-derived ovarian age). The
screening performance was assessed using three different approaches: received
operator curve; detection rate and false positive rates for a fixed 1/250
threshold; and detection rates for a fixed 3% false positive rate. A non
significant trend was shown for AMH-derived age for both an increased area under
the curve (0.986 versus 0.979) and an increased detection rate (from 83% to 100%)
for a 1/250 risk threshold. For a 3% false-positive rate, a non-significant trend
for increased detection with the use of both AMH- and AFC-derived ovarian ages
was observed (from 67% to 83%). These results indicate that, although ovarian
derived ages seem to potentially reflect a more precise background risk for fetal
trisomies, the improvement in screening performance is only residual.
PMID- 27496531
TI - Bullous striae distensae.
PMID- 27496532
TI - Metastatic potential to regional lymph nodes with Gleason score <=7, including
tertiary pattern 5, at radical prostatectomy.
AB - OBJECTIVES: To determine the risk of pelvic lymph node (LN) metastases at radical
prostatectomy (RP) for Gleason score (GS) <=7: 3 + 3 = 6 (grade group [GG]1); 3 +
4 = 7 (GG2); 3 + 4 = 7 (GG2) with tertiary pattern 5 (T5); 4 + 3 = 7 (GG3); 4 + 3
= 7 (GG3) with T5, using the 2014 modified Gleason grading system and the novel
GG system. MATERIALS AND METHODS: We searched our RP database to indentify cases
of GS <=7 prostate cancer with simultaneous pelvic LN dissection (PLND) in the
period between 2005 and 2014. Since 2005, we have graded all glomeruloid and
cribriform cancer as Gleason pattern 4 and have graded mucinous adenocarcinoma
based on the underlying architectural pattern, consistent with the 2014 modified
Gleason grading system. All RPs were embedded in entirety, including the PLND. A
total of 7 442 cases were identified, of which 73 had at least one positive LN
(+LN). RESULTS: The incidence rates for regional LN metastases at RP for 3 + 3 =
6 (GG1), 3 + 4 = 7 (GG2), 3 + 4 = 7 (GG2) with T5, 4 + 3 = 7 (GG3) and 4 + 3 = 7
(GG3) with T5 were 0, 0.6, 0.4, 4.3 and 6.3%, respectively. There was a
statistically significant difference in risk of +LNs at RP between the grade
groups, as defined by the novel GG system. There was no statistically significant
difference in risk of +LNs at RP for men with 3 + 4 (GG2) vs 3 + 4 (GG2) with T5
and for men with 4 + 3 (GG3) vs 4 + 3 (GG3) with T5. Non-pelvic LN involvement
was identified in 0.2% of all RP cases. Two patients with GS 3 + 4 = 7 with <5%
pattern 4 experienced LN metastases. CONCLUSION: This study supports our previous
finding that men with GS 6 (GG1) at RP have no risk of LN metastases. These
findings also support the 2014 revisions to the Gleason grading system where 3 +
3 with T4 (2005 modified grading system) is now considered 3 + 4 (GG2), with a
comment on percent pattern 4, because <5% pattern 4 increases the risk of LN
metastases. It also supports keeping 3 + 4 (GG2) with T5 (<5% pattern 5) and 4 +
3 (GG3) with T5 with their respective grade groups, with a notation of T5 because
the <5% higher grade component did not increase the risk of LN metastases within
a given GG. Our findings highlight that 3 + 4 (GG2) and 4 + 3 (GG3), even with a
5% higher grade component, are distinct groups with respect to LN metastases and
should not be combined under the umbrella designation of GS 7 as is often the
case in the literature with the Gleason grading system.
PMID- 27496533
TI - A One Health approach to antimicrobial resistance surveillance: is there a
business case for it?
AB - Antimicrobial resistance is a global problem of complex epidemiology, suited to a
broad, integrated One Health approach. Resistant organisms exist in humans,
animals, food and the environment, and the main driver of this resistance is
antimicrobial usage. A One Health conceptual framework for surveillance is
presented to include all of these aspects. Global and European (regional and
national) surveillance systems are described, highlighting shortcomings compared
with the framework. Policy decisions rely on economic and scientific evidence, so
the business case for a fully integrated system is presented. The costs of
integrated surveillance are offset by the costs of unchecked resistance and the
benefits arising from interventions and outcomes. Current estimates focus on
costs and benefits of human health outcomes. A One Health assessment includes
wider societal costs of lost labour, changes in health-seeking behaviour, impacts
on animal health and welfare, higher costs of animal-origin food production, and
reduced consumer confidence in safety and international trade of such food.
Benefits of surveillance may take years to realise and are dependent on effective
and accepted interventions. Benefits, including the less tangible, such as
improved synergies and efficiencies in service delivery and more timely and
accurate risk identification, should also be recognised. By including these less
tangible benefits to society, animal welfare, ecosystem health and resilience,
together with the savings and efficiencies through shared resources and social
capital-building, a stronger business case for a One Health approach to
surveillance can be made.
PMID- 27496534
TI - Experiences With the Providers Share Workshop Method: Abortion Worker Support and
Research in Tandem.
AB - Abortion providers work in an environment characterized by the stresses of the
helping professions as well as by the marginalization and devaluation that
accompany work in a stigmatized field. We created the Providers Share Workshop
(PSW), a five-session workshop carried out at seven abortion care sites around
the United States, to support workers and better understand the complexities of
working in abortion care. Qualitative analysis suggests that the experience of
participating in the workshop fosters connection, and that the group process
creates unique data about the abortion care team. Taken together, these results
show that PSW fulfills the dual role of a supportive group intervention-helping
create connections and foster resilience-and a research tool, producing rich,
multi-perspective narratives of the abortion provision team. This method provides
useful insight into supporting abortion care workers specifically, and may also
prove useful in the study and support of other stigmatized workers generally.
PMID- 27496536
TI - Synapse Dysfunction of Layer V Pyramidal Neurons Precedes Neurodegeneration in a
Mouse Model of TDP-43 Proteinopathies.
AB - TDP-43 is a major protein component of pathological neuronal inclusions that are
present in frontotemporal dementia and amyotrophic lateral sclerosis. We report
that TDP-43 plays an important role in dendritic spine formation in the cortex.
The density of spines on YFP+ pyramidal neurons in both the motor and
somatosensory cortex of Thy1-YFP mice, increased significantly from postnatal day
30 (P30), to peak at P60, before being pruned by P90. By comparison, dendritic
spine density was significantly reduced in the motor cortex of Thy1-YFP::TDP
43A315T transgenic mice prior to symptom onset (P60), and in the motor and
somatosensory cortex at symptom onset (P90). Morphological spine-type analysis
revealed that there was a significant impairment in the development of basal
mushroom spines in the motor cortex of Thy1-YFP::TDP-43A315T mice compared to
Thy1-YFP control. Furthermore, reductions in spine density corresponded to
mislocalisation of TDP-43 immunoreactivity and lowered efficacy of synaptic
transmission as determined by electrophysiology at P60. We conclude that mutated
TDP-43 has a significant pathological effect at the dendritic spine that is
associated with attenuated neural transmission.
PMID- 27496535
TI - Quantitative analyses of the hepatic proteome of methylmercury-exposed Atlantic
cod (Gadus morhua) suggest oxidative stress-mediated effects on cellular energy
metabolism.
AB - BACKGROUND: Methylmecury (MeHg) is a widely distributed environmental pollutant
with considerable risk to both human health and wildlife. To gain better insight
into the underlying mechanisms of MeHg-mediated toxicity, we have used label-free
quantitative mass spectrometry to analyze the liver proteome of Atlantic cod
(Gadus morhua) exposed in vivo to MeHg (0, 0.5, 2 mg/kg body weight) for 2 weeks.
RESULTS: Out of a toltal of 1143 proteins quantified, 125 proteins were
differentially regulated between MeHg-treated samples and controls. Using various
bioinformatics tools, we performed gene ontology, pathway and network enrichment
analysis, which indicated that proteins and pathways mainly related to energy
metabolism, antioxidant defense, cytoskeleton remodeling, and protein synthesis
were regulated in the hepatic proteome after MeHg exposure. Comparison with
previous gene expression data strengthened these results, and further supported
that MeHg predominantly affects many energy metabolism pathways, presumably
through its strong induction of oxidative stress. Some enzymes known to have
functionally important oxidation-sensitive cysteine residues in other animals are
among the differentially regulated proteins, suggesting their modulations by MeHg
induced oxidative stress. Integrated analysis of the proteomics dataset combined
with previous gene expression dataset showed a more pronounced effect of MeHg on
amino acid, glucose and fatty acid metabolic pathways, and suggested possible
interactions of the cellular energy metabolism and antioxidant defense pathways.
CONCLUSIONS: MeHg disrupts mainly redox homeostasis and energy generating
metabolic pathways in cod liver. The energy pathways appear to be modulated
through MeHg-induced oxidative stress, possibly mediated by oxidation sensitive
enzymes.
PMID- 27496537
TI - Evaluation of the New World Health Organization Case Definition of Severe Acute
Respiratory Infection for Influenza Surveillance During the Peak Weeks of Two
Influenza Seasons in Quebec, Canada.
AB - During the peak of the 2012-2013 and 2014-2015 influenza seasons in Quebec,
Canada, the sensitivity of the new World Health Organization (WHO) case
definition of severe acute respiratory infection (SARI) in <5-year-old children
was 65% for polymerase chain reaction-confirmed influenza and 79% for other
respiratory viruses (ORVs), whereas its specificity and positive predictive value
were approximately 2- and 4-fold lower for influenza than ORVs (25% vs 40% and
18% vs 76%, respectively). The use of the WHO SARI definition for influenza
surveillance in children should be interpreted with caution according to the
specific surveillance goals.
PMID- 27496539
TI - Does the degree of linguistic experience (native versus nonnative) modulate the
degree to which listeners can benefit from a delay between the onset of the
maskers and the onset of the target speech?
AB - Background noise has a greater adverse effect on word recognition when people are
listening in their second language (L2) as opposed to their first language (L1).
The present study investigates the extent to which linguistic experience affects
the ability of L2 listeners to benefit from a delay between the onset of a masker
and the onset of a word. In a previous study (Ben-David, Tse & Schneider, 2012),
word recognition thresholds for young L1s were found to improve with the increase
in the delay between the onset of a masker (either a stationary noise or a babble
of voices) and the onset of a word. The investigators interpreted this result as
reflecting the ability of L1 listeners to rapidly segregate the target words from
a masker. Given stream segregation depends, in part, on top-down knowledge-driven
processes, we might expect stream segregation to be more "sluggish" for L2
listeners than for L1 listeners, especially when the masker consists of a babble
of L2 voices. In the present study, we compared the ability of native English
speakers to those who had either recent or long-term immersion in English as L2,
to benefit from a delay between masker onset and word onset for English words.
Results show that thresholds were higher for the two L2s groups than for the L1s.
However, the rate at which word recognition improved with word-onset delay was
unaffected by linguistic status, both when words were presented in noise, and in
babble. Hence, for young listeners, stream segregation appears to be independent
of linguistic status, suggesting that bottom-up sensory mechanisms play a large
role in stream segregation in this paradigm. The implications of a failure of
older L1 listeners (in Ben-David et al.) to benefit from a word-onset delay when
the masker is a babble of voices are discussed.
PMID- 27496538
TI - Controlled exploration of the effects of conductive hearing loss on wideband
acoustic immittance in human cadaveric preparations.
AB - Current clinical practice cannot distinguish, with any degree of certainty, the
multiple pathologies that produce conductive hearing loss in patients with an
intact tympanic membrane and a well-aerated middle ear without exploratory
surgery. The lack of an effective non-surgical diagnostic procedure leads to
unnecessary surgery and limits the accuracy of information available during pre
surgical consultations with the patient. A non-invasive measurement to determine
the pathology responsible for a conductive hearing loss prior to surgery would be
of great value. This work investigates the utility of wideband acoustic
immittance (WAI), a non-invasive measure of middle-ear mobility, in the
differential diagnosis of pathologies responsible for conductive hearing loss. We
focus on determining whether power reflectance (PR), a derivative of WAI, is a
possible solution to this problem. PR is a measure of the fraction of sound power
reflected from the middle ear when a sound stimulus is presented to the ear
canal. PR and other metrics of middle-ear performance (such as ossicular motion
via laser Doppler vibrometry) were measured in well-controlled human temporal
bone preparations with simulated pathologies. We report measurements before and
after simulation of stapes fixation (n = 8), malleus fixation (n = 10), ossicular
disarticulation (n = 10), and superior canal dehiscence (n = 8). Our results are
consistent with the small set of previously published reflectance measurements
made in temporal bones and patients. In this present study, these temporal bone
experiments with different middle- and inner-ear pathologies were compared to the
initial normal state by analyzing both WAI and ossicular motion, demonstrating
that WAI can be a valuable tool in the diagnosis of conductive hearing loss.
PMID- 27496540
TI - In vitro proliferation and osteogenic differentiation of human dental pulp stem
cells in injectable thermo-sensitive chitosan/beta
glycerophosphate/hydroxyapatite hydrogel.
AB - Injectable thermo-sensitive hydrogels have a potential application in bone tissue
engineering for their sensitivities and minimal invasive properties. Human dental
pulp stem cells have been considered a promising tool for tissue reconstruction.
The objective of this study was to investigate the proliferation and osteogenic
differentiation of dental pulp stem cells in injectable thermo-sensitive
chitosan/beta-glycerophosphate/hydroxyapatite hydrogel in vitro. The chitosan
/beta-glycerophosphate hydrogel and chitosan/beta-glycerophosphate/hydroxyapatite
hydrogel were prepared using the sol-gel method. The injectability of chitosan
/beta-glycerophosphate hydrogel and chitosan/beta-glycerophosphate/hydroxyapatite
hydrogel was measured using a commercial disposable syringe. Scanning electron
microscopy was used to observe the inner structure of hydrogels. Then dental pulp
stem cells were seeded in chitosan /beta-glycerophosphate hydrogel and
chitosan/beta-glycerophosphate/hydroxyapatite hydrogel, respectively. The growth
of dental pulp stem cells was periodically observed under an inverted microscope.
The proliferation of dental pulp stem cells was detected by using an Alamar Blue
kit, while cell apoptosis was determined by using a Live/Dead
Viability/Cytotoxicity kit. The osteogenic differentiations of dental pulp stem
cells in chitosan /beta-glycerophosphate hydrogel and chitosan/beta
glycerophosphate/hydroxyapatite hydrogel were evaluated by alkaline phosphatase
activity assay and mRNA expression of osteogenesis gene for 21 days in osteogenic
medium. The results indicated that there was no significant difference between
chitosan /beta-glycerophosphate hydrogel and chitosan/beta
glycerophosphate/hydroxyapatite hydrogel in injectability. Cells within the
chitosan/beta-glycerophosphate/hydroxyapatite hydrogel displayed a typical
adherent cell morphology and rapid proliferation with high cellular viability
after 14 days of culture. Dental pulp stem cells seeded in chitosan/beta
glycerophosphate/hydroxyapatite hydrogels had a higher alkaline phosphatase
activity and better up-regulation of gene expression levels of Runx-2, Collagen
I, alkaline phosphatase and osteocalcin than in chitosan /beta-glycerophosphate
hydrogels after osteogenic differentiation. These results demonstrated that the
chitosan/beta-glycerophosphate/hydroxyapatite hydrogel had excellent cellular
compatibility and the superiority in promoting dental pulp stem cells osteogenic
differentiation in vitro, showing that the combination of dental pulp stem cells
and chitosan/beta-glycerophosphate/hydroxyapatite hydrogel has the potential to
be used for bone tissue engineering.
PMID- 27496541
TI - Infectious disease following travel to developed regions: a snapshot of
presentations to an Australian travel medicine clinic.
AB - Much of the travel medicine literature focuses on travel to 'developing' regions
by travellers from 'developed' regions; however literature about travel to
developed regions is scarce. This article examines presentations to a travel
medicine clinic over a 17-year period with illnesses resulting from travel to
developed regions. From a cohort of general presentations to the clinic of 1077
patients, 85 patients acquired infections due to travel to developed regions,
with a total of 99 infectious diagnoses made. This serves to highlight the risk
of infectious disease even among travel to only developed regions, and the
importance of travel advice in these situations.
PMID- 27496542
TI - Osmotic stress adaptation of Paracoccidioides lutzii, Pb01, monitored by
proteomics.
AB - The ability to respond to stressful conditions is essential for most living
organisms. In pathogenic organisms, this response is required for effective
transition from a saprophytic lifestyle to the establishment of pathogenic
interactions within a susceptible host. Hyperosmotic stress has been used as a
model to study signal transduction and seems to cause many cellular adaptations,
including the alteration of protein expression and cellular volume as well as
size regulation. In this work, we evaluated the proteomic profile of
Paracoccidioides lutzii Pb01 yeast cells during osmotic stress induced by
potassium chloride. We performed a high accuracy proteomic technique (NanoUPLC
MS(E)) to identify differentially expressed proteins during osmotic shock. The
data describe an osmoadaptative response of this fungus when subjected to this
treatment. Proteins involved in the synthesis of cell wall components were
modulated, which suggested cell wall remodeling. In addition, alterations in the
energy metabolism were observed. Furthermore, proteins involved in amino acid
metabolism and hydrogen peroxide detoxification were modulated during osmotic
stress. Our study suggests that P. lutzii Pb01. presents a vast osmoadaptative
response that is composed of different proteins that act together to minimize the
effects caused by osmotic stress.
PMID- 27496543
TI - Application of recombinant antigen 5 allergens from seven allergy-relevant
Hymenoptera species in diagnostics.
AB - BACKGROUND: Hymenoptera stings can cause severe anaphylaxis in untreated venom
allergic patients. A correct diagnosis regarding the relevant species for
immunotherapy is often hampered by clinically irrelevant cross-reactivity. In
vespid venom allergy, cross-reactivity between venoms of different species can be
a diagnostic challenge. To address immunological IgE cross-reactivity on
molecular level, seven recombinant antigens 5 of the most important Vespoidea
groups were assessed by different diagnostic setups. METHODS: The antigens 5 of
yellow jackets, hornets, European and American paper wasps, fire ants, white
faced hornets, and Polybia wasps were recombinantly produced in insect cells,
immunologically and structurally characterized, and their sIgE reactivity
assessed by ImmunoCAP, ELISA, cross-inhibition, and basophil activation test
(BAT) in patients with yellow jacket or Polistes venom allergy of two European
geographical areas. RESULTS: All recombinant allergens were correctly folded and
structural models and patient reactivity profiles suggested the presence of
conserved and unique B-cell epitopes. All antigens 5 showed extensive cross
reactivity in sIgE analyses, inhibition assays, and BAT. This cross-reactivity
was more pronounced in ImmunoCAP measurements with venom extracts than in sIgE
analyses with recombinant antigens 5. Dose-response curves with the allergens in
BAT allowed a differentiated individual dissection of relevant sensitization.
CONCLUSIONS: Due to extensive cross-reactivity in various diagnostic settings,
antigens 5 are inappropriate markers for differential sIgE diagnostics in vespid
venom allergy. However, the newly available antigens 5 from further vespid
species and the combination of recombinant allergen-based sIgE measurements with
BAT represents a practicable way to diagnose clinically relevant sensitization in
vespid venom allergy.
PMID- 27496544
TI - Cultural Disparities in the Use of Prescription and Nonprescription Medications
Among Midlife Women in Israel.
AB - The study aimed to examine differences in medication use among midlife women from
different cultural origins and to identify socio-demographic, health, and
lifestyle characteristics associated with prescribed and non-prescribed
medication use. Face-to-face interviews with women aged 45-64 years were
conducted during 2004-2006 within three population groups: long-term Jewish
residents (LTJR), immigrants from the former Soviet Union after 1989, and Arab
women. The survey instrument included current use of medications and way of
purchasing (with/without prescription). The level of prescribed and non
prescribed medication use was categorized as taking none, taking 1-2, and taking
3 or more medications. The rates of medication use were 59.5% for prescribed
medication and 47% for non-prescribed medications. Differences between the
minority groups and LTJR were observed mainly for cardiovascular, vitamins,
supplements, and hormonal medications. The analyses showed significantly lower
use of prescribed medications among immigrants and of non-prescribed medications
among Arab women after taking into account health and socioeconomic indicators.
Increased use of prescribed and non-prescribed medications was associated with
worse health status and older age. Education was associated with increased use of
non-prescribed medications. The disparities in pharmaceutical care may be linked
to barriers in access to health care and to cultural preferences among
minorities.
PMID- 27496545
TI - Experiencing Unmet Medical Needs or Delayed Care Because of Cost: Foreign-Born
Adults in the U.S. by Region of Birth.
AB - Healthy People 2020 in the United States highlights timely access to necessary
health care as a major factor that can reduce health-related disparities. This
study examined the prevalence of delaying/missing necessary health care because
of cost among foreign-born adults (26+ years old) in the United States by their
region of origin, after controlling for geographic clustering at the county and
state levels. METHODS: Using the pooled 2007-2011 National Health Interview
Survey and linked state/county-level data, this study analyzed data on 61,732
foreign-born adults from nine regions of birth. Three-level multilevel modeling
(state > county > individual) was conducted. The age-adjusted percentages of
foreign-born adults who delayed/missed necessary health care because of cost
varied by region of birth, ranging from 7.0% (Southeast Asia) and 11.9% (Europe)
to 15.5% (Mexico/Central America/Caribbean) and 16.7% (the Middle East). However,
after controlling for geographic clustering and other individual-level covariates
(e.g., insurance), adults from Mexico/Central America/Caribbean were less likely
to delay or not receive necessary care compared to their counterparts from all
other parts of the world except for those from Asian regions. This study implies
that disparities can be reduced if some known risk factors (e.g., insurance) are
improved among foreign-born adults.
PMID- 27496546
TI - Trajectory analyses of sickness absence among industrial and municipal employees.
AB - Background: Compared with the public sector, the private sector is more
susceptible to changes in the economic environment and associated threats of
downsizing, outsourcing and transfers of production. This might be assumed to be
associated with more restrictive sickness absence practices. Aims: To investigate
whether this difference is reflected in higher sickness absence rates in the
public sector and to explore the potential of trajectory analysis in researching
such absences. Methods: The sample consisted of industrial and municipal
employees. Latent groups of differential sickness absence during a 6-year study
period were searched with a two-response trajectory analysis that jointly
captured the spells and the days. Multinomial logistic regressions were used to
assess associations of the labour market sector with the set of trajectories
obtained. Results: There were 2207 industrial and 3477 municipal employees in the
study group. The analysis assigned the employees to three trajectory groups, the
'low-level', 'middle-range' and 'high-range' groups. The relative risk ratios for
the middle-range and the high-range trajectories of public sector employees were
not higher after controlling for age, gender and occupational. Conclusions: In
this study, the labour market sector was not a major independent determinant of
sickness absence practices. Trajectory analysis can be recommended as a way to
determine differential absence practices. The trajectory approach might help
occupational health services to identify more accurately the employees who need
support to maintain their work ability.
PMID- 27496547
TI - The effect of multimorbidity on sickness absence by specific diagnoses.
AB - Background: As the world's population ages, the prevalence of multiple chronic
and non-chronic health-related conditions is increasing. Research on
multimorbidity, the co-occurrence of two or more health-related conditions, has
mainly involved patient and older populations. Its effect in working populations,
presumably younger and healthier, is not well known but could conceivably affect
sickness absence (SA) and ability to return to work. Aims: To examine the effect
of multimorbidity on the incidence and duration of SA episodes by frequent
diagnostic groups. Methods: A prospective study (in 2006-2008) of workers in
Spain. Information on health-related conditions was gathered with a standardized
questionnaire and used to construct a sex-specific multidimensional
multimorbidity score (MDMS). In order to estimate the effect of MDMS on incidence
and duration of SA episodes due to cardiovascular diseases (CVD), musculoskeletal
disorders (MSD) and mental health disorders (MHD), we fitted Cox models adjusted
by age, occupational social class and number of prior SA episodes for both sexes.
Results: The study population was 372370. Men with high MDMS showed a trend
towards higher incidence risk for SA due to CVD and MSD [adjusted hazard ratio
(aHR) = 2.03; 95% confidence interval (CI) 1.48-2.78 and aHR = 1.20; 95% CI 1.01
1.43, respectively]. Women showed a similar trend for MSD, but MHD had the
strongest association (aHR = 4.78; 95% CI 1.97-11.62) for high MDMS. In both
sexes, the effect of MDMS was strongest among those without a prior SA. No
consistent associations with SA duration were observed. Conclusions:
Multimorbidity increased the risk of incident musculoskeletal, mental and
cardiovascular SA episodes but not their duration.
PMID- 27496548
TI - Two insulin-like peptides differentially regulate malaria parasite infection in
the mosquito through effects on intermediary metabolism.
AB - Insulin-like peptides (ILPs) play important roles in growth and metabolic
homeostasis, but have also emerged as key regulators of stress responses and
immunity in a variety of vertebrates and invertebrates. Furthermore, a growing
literature suggests that insulin signaling-dependent metabolic provisioning can
influence host responses to infection and affect infection outcomes. In line with
these studies, we previously showed that knockdown of either of two closely
related, infection-induced ILPs, ILP3 and ILP4, in the mosquito Anopheles
stephensi decreased infection with the human malaria parasite Plasmodium
falciparum through kinetically distinct effects on parasite death. However, the
precise mechanisms by which ILP3 and ILP4 control the response to infection
remained unknown. To address this knowledge gap, we used a complementary approach
of direct ILP supplementation into the blood meal to further define ILP-specific
effects on mosquito biology and parasite infection. Notably, we observed that
feeding resulted in differential effects of ILP3 and ILP4 on blood-feeding
behavior and P. falciparum development. These effects depended on ILP-specific
regulation of intermediary metabolism in the mosquito midgut, suggesting a major
contribution of ILP-dependent metabolic shifts to the regulation of infection
resistance and parasite transmission. Accordingly, our data implicate endogenous
ILP signaling in balancing intermediary metabolism for the host response to
infection, affirming this emerging tenet in host-pathogen interactions with novel
insights from a system of significant public health importance.
PMID- 27496549
TI - Two transgenic mouse models for beta-subunit components of succinate-CoA ligase
yielding pleiotropic metabolic alterations.
AB - Succinate-CoA ligase (SUCL) is a heterodimer enzyme composed of Suclg1 alpha
subunit and a substrate-specific Sucla2 or Suclg2 beta-subunit yielding ATP or
GTP, respectively. In humans, the deficiency of this enzyme leads to
encephalomyopathy with or without methylmalonyl aciduria, in addition to
resulting in mitochondrial DNA depletion. We generated mice lacking either one
Sucla2 or Suclg2 allele. Sucla2 heterozygote mice exhibited tissue- and age
dependent decreases in Sucla2 expression associated with decreases in ATP-forming
activity, but rebound increases in cardiac Suclg2 expression and GTP-forming
activity. Bioenergetic parameters including substrate-level phosphorylation (SLP)
were not different between wild-type and Sucla2 heterozygote mice unless a
submaximal pharmacological inhibition of SUCL was concomitantly present. mtDNA
contents were moderately decreased, but blood carnitine esters were significantly
elevated. Suclg2 heterozygote mice exhibited decreases in Suclg2 expression but
no rebound increases in Sucla2 expression or changes in bioenergetic parameters.
Surprisingly, deletion of one Suclg2 allele in Sucla2 heterozygote mice still led
to a rebound but protracted increase in Suclg2 expression, yielding double
heterozygote mice with no alterations in GTP-forming activity or SLP, but more
pronounced changes in mtDNA content and blood carnitine esters, and an increase
in succinate dehydrogenase activity. We conclude that a partial reduction in
Sucla2 elicits rebound increases in Suclg2 expression, which is sufficiently
dominant to overcome even a concomitant deletion of one Suclg2 allele,
pleiotropically affecting metabolic pathways associated with SUCL. These results
as well as the availability of the transgenic mouse colonies will be of value in
understanding SUCL deficiency.
PMID- 27496551
TI - Improved Prediction of Sudden Cardiac Death Risk: Staying Within the
Echocardiogram but Extending Beyond the Ejection Fraction.
PMID- 27496550
TI - Echocardiographic Predictors of Sudden Cardiac Death: The Atherosclerosis Risk in
Communities Study and Cardiovascular Health Study.
AB - BACKGROUND: This study assessed the echocardiographic predictors of sudden
cardiac death (SCD) within 2 population-based cohorts. METHODS AND RESULTS:
Echocardiograms were obtained on 2383 participants (1993-1995) from the ARIC
study (Atherosclerosis Risk in Communities; 100% black) and 5366 participants
(1987-1989 and 1994-1995) from the CHS (Cardiovascular Health Study). The main
outcome was physician-adjudicated SCD. We used Cox proportional-hazards models
with incident coronary heart disease and heart failure as time-dependent
covariates to assess the association between echocardiographic variables and SCD,
adjusting for Framingham risk score variables, coronary heart disease, and renal
function. Cohort-specific results were meta-analyzed. During a median follow-up
of 7.3 and 13.1 years, 44 ARIC study participants and 275 CHS participants had
SCD, respectively. In the meta-analyzed results, the adjusted hazard ratios (95%
confidence intervals) for predictors of SCD were 3.07 (2.29-4.11) for reduced
left ventricular ejection fraction; 1.85 (1.36-2.52) for mitral annular
calcification; 1.64 (1.07-2.51) for mitral E/A >1.5, and 1.52 (1.14-2.02) for
mitral E/A <0.7 (versus mitral E/A 0.7-1.5); 1.30 (1.15-1.48) per 1 SD increase
in left ventricular mass; and 1.15 (1.02-1.30) per 1 SD increase in left atrial
diameter. A receiver-operating characteristic model for prediction of SCD using
Framingham risk score variables had a C statistic of 0.61 for ARIC study and 0.67
for CHS; the full multivariable model including all echocardiographic variables
had a C statistic of 0.76 for ARIC study and 0.74 for CHS. CONCLUSIONS: In
addition to reduced left ventricular ejection fraction, we identified other
echocardiographic-derived variables predictive for SCD that provided incremental
value compared with clinical risk factors.
PMID- 27496552
TI - Cerebral blood flow in small vessel disease: A systematic review and meta
analysis.
AB - White matter hyperintensities are frequent on neuroimaging of older people and
are a key feature of cerebral small vessel disease. They are commonly attributed
to chronic hypoperfusion, although whether low cerebral blood flow is cause or
effect is unclear. We systematically reviewed studies that assessed cerebral
blood flow in small vessel disease patients, performed meta-analysis and
sensitivity analysis of potential confounders. Thirty-eight studies (n = 4006)
met the inclusion criteria, including four longitudinal and 34 cross-sectional
studies. Most cerebral blood flow data were from grey matter. Twenty-four cross
sectional studies (n = 1161) were meta-analysed, showing that cerebral blood flow
was lower in subjects with more white matter hyperintensity, globally and in most
grey and white matter regions (e.g. mean global cerebral blood flow: standardised
mean difference-0.71, 95% CI -1.12, -0.30). These cerebral blood flow differences
were attenuated by excluding studies in dementia or that lacked age-matching.
Four longitudinal studies (n = 1079) gave differing results, e.g., more baseline
white matter hyperintensity predated falling cerebral blood flow (3.9 years, n =
575); cerebral blood flow was low in regions that developed white matter
hyperintensity (1.5 years, n = 40). Cerebral blood flow is lower in subjects with
more white matter hyperintensity cross-sectionally, but evidence for falling
cerebral blood flow predating increasing white matter hyperintensity is
conflicting. Future studies should be longitudinal, obtain more white matter
data, use better age-correction and stratify by clinical diagnosis.
PMID- 27496554
TI - Greenebaum, Stanford Earn Comprehensive Status.
AB - The NCI has granted Comprehensive Cancer Center status to the University of
Maryland's Greenebaum Cancer Center in Baltimore and to the Stanford Cancer
Institute in Palo Alto, CA. They join 45 other cancer centers in achieving this
distinction. The honor recognizes the centers' leadership in cancer research,
education, and clinical care.
PMID- 27496553
TI - Carbogen-induced increases in tumor oxygenation depend on the vascular status of
the tumor: A multiparametric MRI study in two rat glioblastoma models.
AB - The alleviation of hypoxia in glioblastoma with carbogen to improve treatment has
met with limited success. Our hypothesis is that the eventual benefits of
carbogen depend on the capacity for vasodilation. We examined, with MRI, changes
in fractional cerebral blood volume, blood oxygen saturation, and blood
oxygenation level dependent signals in response to carbogen. The analyses were
performed in two xenograft models of glioma (U87 and U251) recognized to have
different vascular patterns. Carbogen increased fractional cerebral blood volume,
blood oxygen saturation, and blood oxygenation level dependent signals in
contralateral tissues. In the tumor core and peritumoral regions, changes were
dependent on the capacity to vasodilate rather than on resting fractional
cerebral blood volume. In the highly vascularised U87 tumor, carbogen induced a
greater increase in fractional cerebral blood volume and blood oxygen saturation
in comparison to the less vascularized U251 tumor. The blood oxygenation level
dependent signal revealed a delayed response in U251 tumors relative to the
contralateral tissue. Additionally, we highlight the considerable heterogeneity
of fractional cerebral blood volume, blood oxygen saturation, and blood
oxygenation level dependent within U251 tumor in which multiple compartments co
exist (tumor core, rim and peritumoral regions). Finally, our study underlines
the complexity of the flow/metabolism interactions in different models of
glioblastoma. These irregularities should be taken into account in order to
palliate intratumoral hypoxia in clinical trials.
PMID- 27496560
TI - Neuropsychiatric disorders in patients with neurocysticercosis.
AB - INTRODUCTION: The purpose of this study was to explore the presence of
neuropsychiatric disorders in patients with neurocysticercosis (NCC). METHOD:
Patients with untreated NCC (n = 45) and healthy controls (n = 45) underwent
psychiatric and neuropsychological assessments. RESULTS: The majority of patients
in the NCC group (64.4%) had at least 1 psychiatric diagnosis, compared with a
minority in the control group (31.1%). The frequency of neurocognitive disorders,
and particularly dementia (major neurocognitive disorder), was significantly
higher in the group of patients with NCC. DISCUSSION: This study confirms the
relationship between NCC and cognitive disorders.
PMID- 27496559
TI - Angiotensin type 2 receptor null mice express reduced levels of renal angiotensin
II type 2 receptor/angiotensin (1-7)/Mas receptor and exhibit greater high-fat
diet-induced kidney injury.
AB - INTRODUCTION: Renin-angiotensin system (RAS) components exert diverse
physiological functions and have been sub-grouped into deleterious angiotensin
converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin type 1 receptor
(AT1R) and protective ACE2/angiotensin (1-7) (Ang-(1-7))/Mas receptor (MasR)
axes. We have reported that chronic activation of angiotensin type 2 receptor
(AT2R) alters RAS components and provides protection against obesity-related
kidney injury. MATERIALS AND METHODS: We utilized AT2R knockout (AT2KO) mice in
this study and evaluated the renal expression of various RAS components and
examined the renal injury after placing these mice on high fat diet (HFD) for 16
weeks. RESULTS: The cortical ACE2 activity and MasR expression were significantly
decreased in AT2KO mice compared to wild type (WT) mice. LC/MS analysis revealed
an increase in renal Ang II levels and a decrease in Ang-(1-7) levels in AT2KO
mice. Cortical expression of ACE and AT1R was increased but renin activity
remained unchanged in AT2KO compared with WT mice. WT mice fed HFD exhibited
increased systolic blood pressure, higher indices of kidney injury, mesangial
matrix expansion score, and microalbuminuria, which were further increased in
AT2KO mice. CONCLUSION: This study suggests that deletion of AT2R decreases the
expression of the beneficial ACE2/Ang-(1-7)/MasR and increases the deleterious
ACE/Ang II/AT1R axis of the renal RAS in mice. Further, AT2KO mice are more
susceptible to HFD-induced renal injury.
PMID- 27496561
TI - Specific oral tolerance induction in childhood.
AB - Food allergy continues to be a significant public health concern for which there
are no approved treatments and management strategies primarily include allergen
avoidance and pharmacological measures for accidental exposures. Food allergy is
thought to result from either a failure to establish oral tolerance or the
breakdown of existing oral tolerance, and therefore, experimental preventative
and treatment strategies are now aimed at inducing specific oral tolerance. This
may occur in infancy prior to the development of food allergy through the optimal
timing of dietary exposure (primary oral tolerance induction) or as a treatment
for established food allergy through oral immunotherapy (secondary oral tolerance
induction). Trials examining the effectiveness of early dietary allergen exposure
to prevent food allergy have yielded promising results for peanut allergy but not
so for other allergens, although the results of several trials are yet to be
published. Although infant feeding guidelines no longer advise to avoid
allergenic foods and exposure to food allergens orally is an important step in
inducing food tolerance by the immune system, evidence regarding the optimal
timing, dose and form of these foods into the infant's diet is lacking. Likewise,
oral immunotherapy trials appear promising for inducing desensitization; however,
the long-term efficacy in achieving sustained desensitization and optimal
protocols to achieve this is unknown. More research is needed in this emerging
field.
PMID- 27496562
TI - Characterization of the response of taurine protons to PRESS at 9.4 T for
Resolving choline and Determining taurine T2.
AB - Point-resolved spectroscopy (PRESS), characterized by two TEs (TE1 and TE2 ), can
be employed to perform animal magnetic resonance spectroscopy (MRS) studies at
9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be
measured by MRS. In this work, the response of the J-coupled protons of Tau as a
function of PRESS TE1 and TE2 was characterized at 9.4 T to achieve two
objectives. The first was to determine two TE1 and TE2 combinations that could be
used to obtain T2 -corrected measures of Tau (3.42 ppm) that were minimally
influenced by J coupling. The second was to exploit the Tau J coupling to find a
timing combination that minimized the 3.25-ppm Tau signal to enable the Cho (3.22
ppm) resonance to be resolved from the overlapping Tau signal. The response of
Tau protons was investigated both numerically and experimentally. It was
numerically determined that the timings {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 ,
TE2 } = {80 ms, 70 ms} yielded similar 3.42-ppm Tau resonance areas (5%
difference), rendering them suitable for Tau T2 determination. {TE1 , TE2 } = {25
ms, 50 ms} was found to yield minimal 3.25-ppm Tau signal, reducing its
interference with Cho. The efficacy of the timings was demonstrated on phantom
solutions and in vivo in four Sprague Dawley rats. LCModel was employed to
analyse the in vivo spectra and Tau T2 values were estimated by fitting the Tau
peak areas obtained with {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms,
70 ms} to a monoexponentially decaying function. An average Tau T2 of 106 ms
(standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra
obtained with {TE1 , TE2 } = {25 ms, 50 ms} demonstrated negligible levels of Tau
signal, compared with that obtained with short TE.
PMID- 27496563
TI - Chronic perfluorooctanesulphonic acid (PFOS) exposure produces estrogenic effects
in zebrafish.
AB - Perfluorooctanesulphonic acid (PFOS) is a ubiquitous contaminant in the aquatic
environment and our earlier studies demonstrated that chronic PFOS exposures lead
to a female-biased sex ratio and decreased sperm quality in male zebrafish. The
underlying mechanism for these reproductive effects is unknown. In the present
study, 8 h post-fertilization (hpf) zebrafish were exposed to PFOS at 250 MUg/L
for 5 months, and the levels of sex hormones, expression of sex determination
related genes, and histological and ultrastructural changes of gonads were fully
characterized. During the sex differentiation period, we observed elevated
estradiol (E2) and decreased testosterone (T) levels in whole tissue homogenates
from PFOS exposed juveniles. In fully mature adult male fish, serum E2 levels
were slightly increased, however, the estrogen receptor alpha (esr1) was
significantly elevated in PFOS treated male gonads. Histological and electron
microscopic examinations revealed structural changes in the gonads of PFOS
exposed male and female adult zebrafish. In summary, chronic PFOS exposure
disrupts sex hormone level and related gene expression and impairs gonadal
development, which may contribute to the previously reported PFOS reproductive
toxicity.
PMID- 27496564
TI - More than 500 million Chinese urban residents (14% of the global urban
population) are imperiled by fine particulate hazard.
AB - China's urbanization and the subsequent public vulnerability to degenerated
environment is important to global public health. Among the environmental
problems, fine particulate (PM2.5) pollution has become a serious hazard in
rapidly urbanizing China. However, quantitative information remains inadequate.
We thus collected PM2.5 concentrations and population census records, to
illustrate the spatial patterns and changes in the PM2.5 hazard levels in China,
and to quantify public vulnerability to the hazard during 2000-2010, following
the air quality standards of World Health Organization. We found that 28% (2.72
million km2) of China's territory, including 78% of cities (154 cities) with a
population of >1 million, was exposed to PM2.5 hazard in 2010; a 15% increase
(1.47 million km2) from 2000 to 2010. The hazards potentially impacted the health
of 72% of the total population (942 million) in 2010, including 70% of the young
(206 million) and 76% of the old (71 million). This was a significant increase
from the 42% of total the population (279 million) exposed in 2000. Of the total
urban residents, 76% (501 million) were affected in 2010. Along with PM2.5
concentration increase, massive number of rural to urban migration also
contributed greatly to China's urban public health vulnerability.
PMID- 27496565
TI - Preparation and preliminary characterization of recombinant neurolysin for in
vivo studies.
AB - The goal of this study was to produce milligram quantities of pure, catalytically
active, endotoxin-free recombinant neurolysin (rNln) in standard laboratory
conditions for use as a research tool. To this end, we transformed E. coli cells
with a plasmid construct for polyhistidine-tagged rNln, selected a high
expressing clone and determined the optimal time-point for translation of rNln.
rNln was purified to homogeneity from the soluble pool of the cell lysate using
Ni-NTA affinity and size-exclusion chromatography, followed by removal of
endotoxins. Using this protocol ~3mg pure, catalytically active and nearly
endotoxin-free (~0.003EU/MUg protein) rNln was reproducibly obtained from 1l of
culture. Lack of cytotoxicity of rNln preparation was documented in cultured
mouse cells, whereas stability in whole mouse blood. Intraperitonealy
administered rNln in mice reached the systemic circulation in intact and
enzymatically active form with Tmax of 1h and T1/2 of ~30min. Administration of
rNln (2 and 10mg/kg) did not alter arterial blood pressure, heart rate, body
temperature and blood glucose levels in mice. These studies demonstrate that the
rNln preparation is suitable for cell culture and in vivo studies and can serve
as a research tool to investigate the (patho)physiological function of this
peptidase.
PMID- 27496566
TI - An omics approach to rational feed: Enhancing growth in CHO cultures with NMR
metabolomics and 2D-DIGE proteomics.
AB - Expression of recombinant proteins exerts stress on cell culture systems,
affecting the expression of endogenous proteins, and contributing to the
depletion of nutrients and accumulation of waste metabolites. In this work, 2D
DIGE proteomics was employed to analyze differential expression of proteins
following stable transfection of a Chinese Hamster Ovary (CHO) cell line to
constitutively express a heavy-chain monoclonal antibody. Thirty-four proteins of
significant differential expression were identified and cross-referenced with
cellular functions and metabolic pathways to identify points of cell stress.
Subsequently, 1D-(1)H NMR metabolomics experiments analyzed cultures to observe
nutrient depletion and waste metabolite accumulations to further examine these
cell stresses and pathways. From among fifty metabolites tracked in time-course,
eight were observed to be completely depleted from the production media,
including: glucose, glutamine, proline, serine, cystine, asparagine, choline, and
hypoxanthine, while twenty-three excreted metabolites were also observed to
accumulate. The differentially expressed proteins, as well as the nutrient
depletion and accumulation of these metabolites corresponded with upregulated
pathways and cell systems related to anaplerotic TCA-replenishment, NADH/NADPH
replenishment, tetrahydrofolate cycle C1 cofactor conversions, limitations to
lipid synthesis, and redox modulation. A nutrient cocktail was assembled to
improve the growth medium and alleviate these cell stresses to achieve a ~75%
improvement to peak cell densities.
PMID- 27496570
TI - [About a case of uterine per-partum rupture, 37months after resection of a
rectovaginal endometriosis nodule].
AB - Endometriosis is a common condition in women, whose main repercussions are
painful symptoms. In addition, it was shown that endometriosis was a major cause
of infertility and various obstetric complications could be related to this
pathology. Uterine rupture is a rare but serious complication whose incidence
tends to decrease with the screening of women at risk, however, its fetal,
maternal morbidity and mortality causes remains important. We were confronted
with a case of posterior uterine rupture in a patient of 36 years, primipare term
exceeded in immediate postpartum period. The patient's primary antecedent of
uterine surgery torus was responsible for infertility endometriosis. The outcome
was favorable for the mother, after a surgical treatment by laparotomy, and for
the child. In the literature, two cases have been reported of uterine rupture
after endometriosis surgery, which is why we found it interesting to report this
rare case. Given the increase in surgical management of this disease, it seems
relevant to ask whether, in the future, we should be more vigilant in monitoring
pregnancy for these women.
PMID- 27496568
TI - Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit
Hepatitis C Virus Infection.
AB - : Hepatitis C virus (HCV) is a significant global public health problem, causing
more than 350,000 deaths every year. Although the development of direct-acting
antivirals has improved the sustained virological response rate in HCV patients,
novel anti-HCV agents with higher efficacy as well as better tolerance and
cheaper production costs are still urgently needed. Cell-based therapy,
especially its unique and strong paracrine ability to transfer information to
other cells via extracellular vesicles such as exosomes, has become one of the
most popular therapeutic methods in recent years. In our study, exosomes secreted
from umbilical mesenchymal stem cells (uMSCs), which are widely used in
regenerative medicine, inhibited HCV infection in vitro, especially viral
replication, with low cell toxicity. Our analysis revealed that microRNAs
(miRNAs) from uMSC-derived exosomes (uMSC-Exo) had their unique expression
profiles, and these functional miRNAs, mainly represented by let-7f, miR-145, miR
199a, and miR-221 released from uMSC-Exo, largely contributed to the suppression
of HCV RNA replication. These four miRNAs possessed binding sites in HCV RNA as
demonstrated by the target prediction algorithm. In addition, uMSC-Exo therapy
showed synergistic effect when combined with U.S. Food and Drug Administration
approved interferon-alpha or telaprevir, enhancing their anti-HCV ability and
thus improving the clinical significance of these regenerative substances for
future application as optimal adjuvants of anti-HCV therapy. SIGNIFICANCE: This
work reported, for the first time, the identification of stem cell-derived
exosomes of antiviral activity. Umbilical mesenchymal stem cell-secreted exosomes
inhibited hepatitis C virus infection through transporting a mixture of microRNAs
complementing the viral genomes to the host cells. This finding provides insights
and prospects for physiologically secreted substances for antiviral therapy.
PMID- 27496571
TI - [Does the paper speed in fetal heart monitoring during labour influence the
variability in the interpretation by professionals?]
AB - OBJECTIVE: Assessing inter- and intra- observer agreement in the reading of fetal
heart rate (FHR) between two different paper speeds (1 and 2cm/min) using FIGO
classification. MATERIAL AND METHODS: Single-centre experimental study consisting
in reading 60minutes FHR tracings by six readers (3 midwives and 3 obstetricians)
during 1cm and 2cm/min sessions within a period of three weeks. The reading
guideline was based on FIGO classification. Inter- and intra-observer agreement
was assessed thanks to Kappa coefficient (K) and percentage of agreement (PA)
using the classification of FHR tracings drawn up by readers. RESULTS: Intra
observer agreement reached 60% between the two paper speeds, and PA ranged from
48 to 67%. Inter-observer agreement was poor to moderate (K=0.42 for 1cm/min
sessions and K=0.38 for 2cm/min sessions). Inter-observer agreement was
significantly higher for normal tracings (PA ranged from 55.2% for 2cm/min
sessions to 57.4% for 1cm/min sessions). The preterminal category had the lowest
concordance rates (PA=19% for 1cm/min sessions and 20, 7% for 2cm/min sessions).
CONCLUSION: This study did not highlight significant differences in intra- and
inter-observer variability between the two FHR paper speeds. The 1cm/min paper
speed, which is commonly used in France, is more economical and gives a better
bedside overview of FHR. Therefore, it should be recommended.
PMID- 27496572
TI - Microglial role in the development of chronic pain.
AB - PURPOSE OF REVIEW: The review aims to present the latest research into microglia
and their role in pain. RECENT FINDINGS: Microglia affect sex and age-dependent
differences in pain. The various microglial phenotypes make their involvement in
pain more complex but provide more potential as pain modulators. SUMMARY: Glial
cells, composed of microglia, astrocytes, and oligodendrocytes, outnumber neurons
in the central nervous system. The crosstalk between these cells and neurons is
now established as participating in the development of chronic pain. There has
been a great advance in the description of microglia reactivity from pro to anti
inflammatory phenotypes. The modulation of these phenotypes could be a potential
target for pain therapy. Recently, different microglial reactivity between man
and woman and between neonates and adults, in response to nerve injury were
described, which could explain some of the sex differences in pain sensitivity
and the absence of neuropathic pain development in neonates. Clinical trials
using microglia as a target have been carried out in various neurological
diseases and pain, with limited efficacy in the latter, but there are
nonetheless, indications that with some improvement in study strategies microglia
could be a future target for pain control.
PMID- 27496573
TI - A systematic review and meta-analysis of randomised controlled trials of
treatments for clozapine-induced obesity and metabolic syndrome.
AB - Metabolic complications are commonly found in people treated with clozapine.
Reviews on the management of this problem have generally drawn conclusions by
grouping different types of studies involving patients treated with various
different antipsychotics. We carried out a systematic review and meta-analysis of
pharmacological and non-pharmacological treatments for clozapine-induced obesity
or metabolic syndrome. Two researchers independently searched PubMed and Embase
for randomised controlled trials (RCTs) of treatments for clozapine-induced
obesity or metabolic syndrome. All other types of studies were excluded. We only
included RCTs where more than 50% of participants were taking clozapine. We
identified 15 RCTs. Effective pharmacological treatments for clozapine-induced
obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in
men only). Meta-analysis of three studies showed a robust effect of metformin in
reducing body mass index and waist circumference but no effects on blood glucose,
triglyceride levels, or HDL levels. In addition, there is limited evidence for
combined calorie restriction and exercise as a non-pharmacological alternative
for the treatment of clozapine-induced obesity, but only in an in-patient
setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil,
and atomoxetine have not shown to be beneficial, despite reports of efficacy in
other populations treated with different antipsychotics. We conclude that
randomised-controlled trial data support the use of metformin, aripiprazole, and
Orlistat (in men only) for treating clozapine-induced obesity. Calorie
restriction in combination with an exercise programme may be effective as a non
pharmacological alternative. Findings from trials in different populations should
not be extrapolated to people being treated with clozapine.
PMID- 27496574
TI - Anticipation: Beyond synthetic biology and cognitive robotics.
AB - The aim of this paper is to propose that current robotic technologies cannot have
intentional states any more than is feasible within the sensorimotor variant of
embodied cognition. It argues that anticipation is an emerging concept that can
provide a bridge between both the deepest philosophical theories about the nature
of life and cognition and the empirical biological and cognitive sciences steeped
in reductionist and Newtonian conceptions of causality. The paper advocates that
in order to move forward, cognitive robotics needs to embrace new platforms and a
conceptual framework that will enable it to pursue, in a meaningful way,
questions about autonomy and purposeful behaviour. We suggest that hybrid
systems, part robotic and part cultures of neurones, offer experimental platforms
where different dimensions of enactivism (sensorimotor, constitutive foundations
of biological autonomy, including anticipation), and their relative contributions
to cognition, can be investigated in an integrated way. A careful progression,
mindful to the deep philosophical concerns but also respecting empirical
evidence, will ultimately lead towards unifying theoretical and empirical
biological sciences and may offer advancement where reductionist sciences have
been so far faltering.
PMID- 27496575
TI - Cyst-like lesion in mandibular coronoid process: an unusual location.
PMID- 27496576
TI - Biologic and clinical aspects of integration of different bone substitutes in
oral surgery: a literature review.
AB - Many bone substitutes have been proposed for bone regeneration, and researchers
have focused on the interactions occurring between grafts and host tissue, as the
biologic response of host tissue is related to the origin of the biomaterial.
Bone substitutes used in oral and maxillofacial surgery could be categorized
according to their biologic origin and source as autologous bone graft when
obtained from the same individual receiving the graft; homologous bone graft, or
allograft, when harvested from an individual other than the one receiving the
graft; animal-derived heterologous bone graft, or xenograft, when derived from a
species other than human; and alloplastic graft, made of bone substitute of
synthetic origin. The aim of this review is to describe the most commonly used
bone substitutes, according to their origin, and to focus on the biologic events
that ultimately lead to the integration of a biomaterial with the host tissue.
PMID- 27496578
TI - Follow-up of oral cancer patients: three uneventful years may be enough.
AB - OBJECTIVE: To explore the possibility of shortening the length of follow-up from
5 to 3 years in patients who have undergone curative treatment of an oral
squamous cell carcinoma. STUDY DESIGN: The medical records of 225 patients who
had undergone initial curative treatment at the VU University Medical Center in
Amsterdam, the Netherlands, between 2004 and 2009 were analyzed. RESULTS: In 96
patients (42.7%) a secondary event occurred. Eighty-six percent of the secondary
events were detected within 3 years. In the fourth and fifth years, 14% of the
secondary events were found, consisting mainly of second primary tumors.
CONCLUSIONS: Most secondary events occurred within the first 3 years of follow
up. Therefore, the case can be made for an altered regimen of follow-up beyond 3
years based on certain risk factors unique to the patient as well as the
patient's ability to adequately report symptoms that may be associated with
recurrent disease.
PMID- 27496577
TI - Intramuscular botulinum toxin injection additional to arthrocentesis in the
management of temporomandibular joint pain.
AB - OBJECTIVE: The aim of this study was to compare the effect of intramuscular
injection of botulinum toxin (BTX-A) as an adjunct to arthrocentesis with the
effect of BTX-A injections alone in the treatment of temporomandibular joint
disorders (TMDs) with masticatory muscles tension. STUDY DESIGN: The clinical
study included 20 TMD patients divided into 2 groups. The influence of daily
activities on pain in the temporomandibular joint (TMJ) area was evaluated in
both groups using the rating scale by List and Helkimo. Range of maximal
interincisial opening (MIO) and joint pain as measured by the visual analogue
scale (VAS) were examined to determine the clinical efficiency of the procedures
before and after treatment. Group A consisted of 12 patients; they were treated
with arthrocentesis and BTX-A injections in the temporal and masseter muscles.
Group B consisted of 8 patients; they had only BTX-A injections in the same
muscles as mentioned. RESULTS: In group A, VAS decreased significantly (P =
.005), and MIO improved significantly (P < .005). CONCLUSIONS: Arthrocentesis
with BTX-A seems to affect the clinical outcomes with regard to MIO and VAS
compared with the results when BTX-A only was used. BTX-A in combination with
arthrocentesis improved the TMJ area symptoms.
PMID- 27496579
TI - Water soluble extracts from Actinidia arguta, PG102, attenuates house dust mite
induced murine atopic dermatitis by inhibiting the mTOR pathway with Treg
generation.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia arguta is widespread in northeastern
Asia, being found in Siberia, Korea, Japan, and northern China. These fruits have
been documented to regulate the uncontrolled heat of body resulting in various
allergic diseases in the Korean traditional medicine. PG102, a water-soluble
extract from an edible fruit, A. arguta, has been previously shown to control
various factors involved in allergic pathogenesis. AIM OF THE STUDY: In this
study, we investigated whether PG102 prevents chronic allergic reactions via the
generation of Tregs, which play a preventive role in the pathogenesis of allergic
disease. METHODS AND RESULTS: In dust mite extract-induced chronic atopic
dermatitis, orally administered PG102 inhibited symptoms of dermatitis, including
ear swelling and erythema, and decreased lymphocyte infiltration into the
inflamed region. Moreover, PG102 reduced inflammatory T cell responses and
increased the expression levels of Foxp3 and other Treg-related genes. PG102
treatment enhanced the induction of CD4+Foxp3+ Tregs from naive CD4+CD62L+ T
cells, probably via the inhibition of mTOR activation and the phosphorylation of
STAT5 rather than using the TGF-beta signaling pathway. CONCLUSION: PG102 may
have potential as an orally active immunosuppressor for preventing chronic
inflammatory diseases.
PMID- 27496580
TI - Chyawanprash: A review of therapeutic benefits as in authoritative texts and
documented clinical literature.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Chyawanprash (CP), a traditional immune booster
recipe, has a long history of ethnic origin, development, household preparation
and usage. There are even mythological stories about the origin of this recipe
including its nomenclature. In the last six decades, CP, because of
entrepreneurial actions of some research Vaidyas (traditional doctors) has grown
to industrial production and marketing in packed forms to a large number of
consumers/patients like any food or health care product. Currently, CP has
acquired a large accepted user base in India and in a few countries out-side
India. AIM OF THE STUDY: Authoritative texts, recognized by the Drugs and
Cosmetics Act of India, describe CP as an immunity enhancer and strength giver
meant for improving lung functions in diseases with compromised immunity. This
review focuses on published clinical efficacy and safety studies of CP for
correlation with health benefits as documented in the authoritative texts, and
also briefs on its recipes and processes. MATERIALS AND METHODS: Authoritative
texts were searched for recipes, processes, and other technical details of CP.
Labels of marketing CP products (Indian) were studied for the health claims.
Electronic search for studies of CP on efficacy and safety data were performed in
PubMed/MEDLINE and DHARA (Digital Helpline for Ayurveda Research Articles), and
Ayurvedic books were also searched for clinical studies. RESULTS: The documented
clinical studies from electronic databases and Ayurvedic books evidenced that
individuals who consume CP regularly for a definite period of time showed
improvement in overall health status and immunity. However, most of the clinical
studies in this review are of smaller sample size and short duration. Further,
limitation to access and review significant data on traditional products like CP
in electronic databases was noted. CONCLUSIONS: Randomized controlled trials of
high quality with larger sample size and longer follow-up are needed to have
significant evidence on the clinical use of CP as immunity booster. Additional
studies involving measurement of current biomarkers of immunity pre- and post
consumption of the product as well as benefits accruing with the use of CP as an
adjuvant are suggested.
PMID- 27496581
TI - Use of plants in oral health care by the population of Mahajanga, Madagascar.
AB - BACKGROUND: The use of medicinal plants to address oral health problems is not
well documented in Madagascar, yet the country is full of endemic flora. The aim
of this study was to collect information on the use of plants in the region of
Mahajanga, Madagascar, for the treatments of oral diseases mainly tooth decay.
METHODS: The ethnobotanical survey with respect to the use of plants for curing
dental problems was carried out in 2012. A cluster sampling at three levels was
applied when choosing the study sites. The target population was made up of heads
of household. The following data were collected from a semi-structured
questionnaire: name of plants, part used, mode of preparation, and
administration. The Informant Consensus Factor and Fidelity Level indexes were
calculated for each condition treated and used plants. The Results revealed that
93 per cent of the targeted population has used plants to calm dental pain,
whereas 44.2% have reported using plants due to financial problems. About 65
species of plants are commonly used for oral health care and 63 of them treated
caries. Cajanus cajan (L.) Millsp. was the most plant used. It was mostly used in
crushed form of 5 to 9 leaves which were prepared and placed directly on the
affected oral part or in the tooth cavity. In general, the treatment lasted about
5 days or minus. The ICF were 0.83 for caries and 0.81 for periodontal diseases.
CONCLUSION: This ethnobotanical survey will serve as database for further
phytochemical and pharmacological study of plants in order to identify their
active components and advise the population on the most effective administration.
PMID- 27496582
TI - Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and
prediabetes: A meta-analysis.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Fenugreek is a widely used herb for the treatment
of diabetes mellitus (DM) but the effects in randomized controlled trials (RCTs)
were controversial. Therefore, a meta-analysis was conducted to estimate the
overall effects of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and
prediabetes. MATERIALS AND METHODS: PubMed, EMBASE, web of science, Chinese
Biomedical Literature database (CBM), the Cochrane library, China Doctor
Dissertations Full-text Database (CDFD), Wan Fang medical database, China
Proceedings of Conference Full-text Database (CPCD), China national knowledge
internet (CNKI) and China Master's Theses Full-text Database (CMFD) were searched
to find the available literatures. RCTs with regard to the efficacy and safety of
fenugreek on prediabetes or DM were included. The data of fasting blood glucose
(FBG), postprandial 2h blood glucose (2hBG), glycosylated hemoglobin (HbA1c),
triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol
(LDL-c) and high density lipoprotein cholesterol (HDL-c) were extracted to
appraise the net change with fixed or randomized effect model. RESULTS: A total
of 10 articles (12 studies) were included in the analysis. Pooled results showed
fenugreek significantly decreased the levels of FBG (MD -0.84mmol/L; 95% CI -1.38
to -0.31; p=0.002), 2hBG (MD -1.30mmol/L; 95% CI -1.78 to -0.83; p<0.0001), HbA1c
(MD -1.16; 95% CI -1.23 to -1.09; p<0.00001) and TC (MD -0.30mmol/L; 95% CI-0.56
to -0.03; p=0.03). In spite of the reductive trends in the TG or LDL-c levels and
incremental trends of HDL-c, these results were not statistically significant or
need further verification for fenugreek in the treatment of DM and prediabetes.
Some studies were of low quality. No liver and kidney toxicity were found in all
included studies, and the main side effects were gastrointestinal discomfort.
CONCLUSIONS: The results suggest fenugreek has the hypoglycaemic and TC-lowering
efficacy; however, the effects on TG, LDL-c and HDL-c need further confirmations.
PMID- 27496583
TI - Ameliorative effect of two Ayurvedic herbs on experimentally induced arsenic
toxicity in calves.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Chronic arsenic poisoning due to contaminated
subsoil water is a threat to society in West Bengal, India and in Bangladesh. The
human being may also be affected by the exposed cattle from the affected area by
consuming milk, egg, meat and others. In Ayurveda, several herbs like Haridra
(turmeric), Shunthi (dried ginger root) and others are used for the management of
arsenic poisoning. AIM OF THE STUDY: The study was conducted to find out the
ameliorative effect of turmeric and ginger powder against experimentally induced
arsenic toxicity in calves. MATERIALS AND METHODS: Twenty four calves were
divided into four groups (group I, II, III and IV) having six animals in each
group. Animals of group I, II and III were orally administered with sodium
arsenite at 1mg/kg body weight for 90 days and in addition group II and group III
animals were treated orally with turmeric and ginger powder respectively at
10mg/kg body weight from 46th day onwards. Group IV animals were given food and
water without drug and served as control. Arsenic content was estimated in
faeces, hair, urine and plasma in every 15 days. Bio-chemical, haematological and
anti-oxidant parameters were also assessed. RESULTS: Turmeric and ginger powder
significantly (P<0.05) reduced the plasma and hair arsenic levels through
increased excretion via faeces and urine. Haemoglobin level, TEC and TLC were
decreased in groups I, II and III, however these were improved significantly
(P<0.05) from 75th day onwards in turmeric and ginger treated groups. Increased
activity of AST and ALT were significantly decreased (P<0.05) from 75th day
onwards in group II and III. Blood urea nitrogen and plasma creatinine were also
significantly decreased (P<0.05) in group II and III than group I from 60th day
onwards. The SOD and catalase activity were significantly (P<0.05) reduced in
groups I, II and III, but these were restored at the end of the experiment in
turmeric and ginger treated groups. CONCLUSION: The test drugs are found
significantly effective not only to eliminate arsenic from the body but also give
protection from possible damage caused by arsenic exposure, it may be concluded
from the present study that turmeric and ginger can be helpful in the therapy of
chronic arsenic toxicity in calves.
PMID- 27496584
TI - The Influence of Nurse Manager Leadership Style on Staff Nurse Work Engagement.
AB - BACKGROUND: Nursing literature supports the importance of an engaged nursing
workforce as a means to positively influence performance. Nurse manager
leadership style plays a critical role in engaging staff nurses. These
relationships have been minimally studied in nurse managers and staff nurses.
OBJECTIVE: The aim of this study is to evaluate the influence of nurse manager
leadership style factors on staff nurse work engagement. METHODS: Using a
descriptive correlational research design, 441 staff nurses working in 3 acute
care hospitals were surveyed. Survey instruments included the Utrecht Work
Engagement Scale and the Multifactorial Leadership Questionnaire 5X short form.
RESULTS: Transactional and transformational leadership styles in nurse managers
positively influenced staff nurse work engagement. Passive-avoidant leadership
style in nurse managers negatively influenced staff nurse work engagement.
CONCLUSIONS: Nurse managers who provide support and communication through
transformational and transactional leadership styles can have a positive impact
on staff nurse work engagement and ultimately improve organizational outcomes.
PMID- 27496585
TI - Ventricular extrasystoles and ventricular dysfunction: Too close for comfort?
PMID- 27496586
TI - Comparative study of the failure rates among 3 implantable defibrillator leads.
AB - BACKGROUND: After the introduction of the Biotronik Linox S/SD high-voltage lead,
several cases of early failure have been observed. OBJECTIVE: The purpose of this
article was to assess the performance of the Linox S/SD lead in comparison to 2
other contemporary leads. METHODS: We used the prospective Erasmus MC ICD
registry to identify all implanted Linox S/SD (n = 408), Durata (St. Jude
Medical, model 7122) (n = 340), and Endotak Reliance (Boston Scientific, models
0155, 0138, and 0158) (n = 343) leads. Lead failure was defined by low- or high
voltage impedance, failure to capture, sense or defibrillate, or the presence of
nonphysiological signals not due to external interference. RESULTS: During a
median follow-up of 5.1 years, 24 Linox (5.9%), 5 Endotak (1.5%), and 5 Durata
(1.5%) leads failed. At 5-year follow-up, the cumulative failure rate of Linox
leads (6.4%) was higher than that of Endotak (0.4%; P < .0001) and Durata (2.0%;
P = .003) leads. The incidence rate was higher in Linox leads (1.3 per 100
patient-years) than in Endotak and Durata leads (0.2 and 0.3 per 100 patient
years, respectively; P < .001). A log-log analysis of the cumulative hazard for
Linox leads functioning at 3-year follow-up revealed a stable failure rate of 3%
per year. The majority of failures consisted of noise (62.5%) and abnormal
impedance (33.3%). CONCLUSION: This study demonstrates a higher failure rate of
Linox S/SD high-voltage leads compared to contemporary leads. Although the
mechanism of lead failure is unclear, the majority presents with abnormal
electrical parameters. Comprehensive monitoring of Linox S/SD high-voltage leads
includes remote monitoring to facilitate early detection of lead failure.
PMID- 27496587
TI - Melody and rhythm in congenital heart disease.
PMID- 27496588
TI - Demethylation and re-methylation dynamics in transgenerational epigenetic
inheritance.
PMID- 27496589
TI - Intravenous Heroin Abuse and Acute Myocardial Infarction: Association or
Causality?
PMID- 27496590
TI - Children on the autism spectrum update their behaviour in response to a volatile
environment.
AB - Typical adults can track reward probabilities across trials to estimate the
volatility of the environment and use this information to modify their learning
rate (Behrens et al., 2007). In a stable environment, it is advantageous to take
account of outcomes over many trials, whereas in a volatile environment, recent
experience should be more strongly weighted than distant experience. Recent
predictive coding accounts of autism propose that autistic individuals will
demonstrate atypical updating of their behaviour in response to the statistics of
the reward environment. To rigorously test this hypothesis, we administered a
developmentally appropriate version of Behrens et al.'s (2007) task to 34
cognitively able children on the autism spectrum aged between 6 and 14 years, 32
age- and ability-matched typically developing children and 19 typical adults.
Participants were required to choose between a green and a blue pirate chest,
each associated with a randomly determined reward value between 0 and 100 points,
with a combined total of 100 points. On each trial, the reward was given for one
stimulus only. In the stable condition, the ratio of the blue or green response
being rewarded was fixed at 75:25. In the volatile condition, the ratio
alternated between 80:20 and 20:80 every 20 trials. We estimated the learning
rate for each participant by fitting a delta rule model and compared this rate
across conditions and groups. All groups increased their learning rate in the
volatile condition compared to the stable condition. Unexpectedly, there was no
effect of group and no interaction between group and condition. Thus, autistic
children used information about the statistics of the reward environment to guide
their decisions to a similar extent as typically developing children and adults.
These results help constrain predictive coding accounts of autism by
demonstrating that autism is not characterized by uniform differences in the
weighting of prediction error.
PMID- 27496591
TI - A single center experience of Zilver PTX for femoro-popliteal lesions.
AB - BACKGROUND: Clinical trial data show overall favorable outcomes of paclitaxel
eluting stents for treatment of femoro-popliteal (FP) occlusive disease. However,
external validity of trial results may be restricted to less complex FP lesions,
and limited data on outcomes of paclitaxel-eluting stents in real world practice
have been published. METHODS: This is a retrospective analysis of data of all
patients who received Zilver(r) PTX(r) for FP lesion from February 2013 to
October 2014 at our center. The primary endpoint was primary patency, defined as
peak systolic velocity ratio <2.0 by Doppler ultrasound, or angiographic diameter
stenosis <50%, or freedom from clinically driven target lesion revascularization.
RESULTS: Seventy-eight patients received Zilver(r) PTX(r) for FP lesions in the
pre-specified time period. Of them, 63 had follow-up data and were included in
this study. Mean patient age was 66.3+/-9.4years, and 57.1% of the patients were
men. Participants had a high prevalence of diabetes (49.2%), hypertension
(93.7%), hyperlipidemia (93.7%), previous coronary revascularization (52.4%), or
previous peripheral arterial disease (77.8%). Critical limb ischemia was present
in 25.4% of the patients, Trans-Atlantic Inter-Society Consensus (TASC) class C
or D in 76.2%, in-stent restenosis (ISR) in 36.5%, and total occlusion in 69.8%.
Mean lesion length was 218.9+/-128.3mm, mean number of stents was 2.02+/-1.0, and
total stent length was 189.0+/-128.5mm. Mean follow-up was 270.4+/-190.3days.
Primary patency rate at 1year was 66.7% by Kaplan-Meier survival curve. When
compared with patients with primary patency at follow up, those with an adverse
outcome had higher prevalence of TASC II class C or D lesions (100% vs. 68.8%,
p=0.013), and were more likely to have ISR (66.7% vs. 27.1%, p=0.012), longer
lesion (291.3+/-138.7 vs. 195.7+/-117.1, p=0.011), and incomplete coverage of the
lesion (full coverage of lesions: 40% vs. 77.1%, p=0.011). CONCLUSION: Post
marketing use of Zilver(r) PTX(r) for the treatment of FP lesions is associated
with lower patency rates compared with clinical trial data. This may be related
to the high prevalence of TASC II class C or D lesions and ISR in real world
practice. Future studies should be more representative of contemporary clinical
practice.
PMID- 27496592
TI - Prevalence of Mycobacterium tuberculosis Beijing genotype and its association
with drug resistance in North India.
AB - The global presence and rapid dissemination of Beijing genotype of Mycobacterium
tuberculosis, makes it an important issue of public health. Its presence and
association with multi-drug resistance has been shown in many settings. In
present study we tried to find its prevalence and association with drug
resistance in North India. One hundred and twenty four M. tuberculosis isolates
were analyzed with spoligotyping, further drug susceptibility testing was done by
1% proportional method. Out of these, 11 (8.9%) M. tuberculosis isolates were
identified as Beijing and 113 (91.1%) as non-Beijing genotypes. While looking at
their drug susceptibility patterns, 6 (54.5%) & 22 (19.5%) were found to be multi
drug resistant (MDR) among Beijing and non-Beijing isolates respectively. Our
study concluded that the Beijing strains were not so common in north India and
these strains do not fully associate with MDR.
PMID- 27496593
TI - Prioritizing the mHealth Design Space: A Mixed-Methods Analysis of Smokers'
Perspectives.
AB - BACKGROUND: Smoking remains the leading cause of preventable disease and death in
the United States. Therefore, researchers are constantly exploring new ways to
promote smoking cessation. Mobile health (mHealth) technologies could be
effective cessation tools. Despite the availability of commercial quit-smoking
apps, little research to date has examined smokers' preferred treatment
intervention components (ie, design features). Honoring these preferences is
important for designing programs that are appealing to smokers and may be more
likely to be adopted and used. OBJECTIVE: The aim of this study was to understand
smokers' preferred design features of mHealth quit-smoking tools. METHODS: We
used a mixed-methods approach consisting of focus groups and written surveys to
understand the design preferences of adult smokers who were interested in
quitting smoking (N=40). Focus groups were stratified by age to allow differing
perspectives to emerge between older (>40 years) and younger (<40 years)
participants. Focus group discussion included a "blue-sky" brainstorming exercise
followed by participant reactions to contrasting design options for communicating
with smokers, providing social support, and incentivizing program use.
Participants rated the importance of preselected design features on an exit
survey. Qualitative analyses examined emergent discussion themes and quantitative
analyses compared feature ratings to determine which were perceived as most
important. RESULTS: Participants preferred a highly personalized and adaptive
mHealth experience. Their ideal mHealth quit-smoking tool would allow
personalized tracking of their progress, adaptively tailored feedback, and real
time peer support to help manage smoking cravings. Based on qualitative analysis
of focus group discussion, participants preferred pull messages (ie, delivered
upon request) over push messages (ie, sent automatically) and preferred
interaction with other smokers through closed social networks. Preferences for
entertaining games or other rewarding incentives to encourage program use
differed by age group. Based on quantitative analysis of surveys, participants
rated the importance of select design features significantly differently
(P<.001). Design features rated as most important included personalized content,
the ability to track one's progress, and features designed to help manage
nicotine withdrawal and medication side effects. Design features rated least
important were quit-smoking videos and posting on social media. Communicating
with stop-smoking experts was rated more important than communicating with family
and friends about quitting (P=.03). Perceived importance of various design
features varied by age, experience with technology, and frequency of smoking.
CONCLUSIONS: Future mHealth cessation aids should be designed with an
understanding of smokers' needs and preferences for these tools. Doing so does
not guarantee treatment effectiveness, but balancing user preferences with best
practice treatment considerations could enhance program adoption and improve
treatment outcomes. Grounded in the perspectives of smokers, we identify several
design considerations, which should be prioritized when designing future mHealth
cessation tools and which warrant additional empirical validation.
PMID- 27496594
TI - Towards the development of a sustainable soya bean-based feedstock for
aquaculture.
AB - Soya bean (Glycine max (L.) Merr.) is sought after for both its oil and protein
components. Genetic approaches to add value to either component are ongoing
efforts in soya bean breeding and molecular biology programmes. The former is the
primary vegetable oil consumed in the world. Hence, its primary usage is in
direct human consumption. As a means to increase its utility in feed
applications, thereby expanding the market of soya bean coproducts, we
investigated the simultaneous displacement of marine ingredients in aquafeeds
with soya bean-based protein and a high Omega-3 fatty acid soya bean oil,
enriched with alpha-linolenic and stearidonic acids, in both steelhead trout
(Oncorhynchus mykiss) and Kampachi (Seriola rivoliana). Communicated herein are
aquafeed formulations with major reduction in marine ingredients that translates
to more total Omega-3 fatty acids in harvested flesh. Building off of these
findings, subsequent efforts were directed towards a genetic strategy that would
translate to a prototype design of an optimal identity-preserved soya bean-based
feedstock for aquaculture, whereby a multigene stack approach for the targeted
synthesis of two value-added output traits, eicosapentaenoic acid and the
ketocarotenoid, astaxanthin, were introduced into the crop. To this end, the
systematic introduction of seven transgenic cassettes into soya bean, and the
molecular and phenotypic evaluation of the derived novel events are described.
PMID- 27496595
TI - Antihistamine updosing reduces disease activity in patients with difficult-to
treat cholinergic urticaria.
PMID- 27496596
TI - Half-life of IgE in serum and skin: Consequences for anti-IgE therapy in patients
with allergic disease.
AB - We present results from clinical studies on plasma infusion done in the late
1970s in patients with hypogammaglobulinemia in which we documented the short
half-life of both total and allergen-specific IgE in serum. The development of
specific allergic sensitization in the skin of those patients followed by the
gradual decrease in sensitization over 50 days was also documented. The data are
included here along with a discussion of the existing literature about the half
life of IgE in both the circulation and skin. This rostrum reinterprets the
earlier clinical studies in light of new insights and mechanisms that could
explain the rapid removal of IgE from the circulation. These mechanisms have
clinical implications that relate to the increasing use of anti-IgE mAbs for the
treatment of allergic disease.
PMID- 27496597
TI - Psychological dependence on antidepressants in patients with panic disorder: a
cross-sectional study.
AB - No study has investigated psychological dependence on antidepressants in patients
with panic disorder, which was addressed in this study. This study was carried
out in four psychiatric clinics in Tokyo, Japan. Individuals were eligible if
they were outpatients aged 18 years or older and fulfilled the diagnostic
criteria for panic disorder (ICD-10). Assessments included the Japanese Versions
of the Severity of Dependence Scale (SDS), the Self-Report Version of Panic
Disorder Severity Scale (PDSS-SR), and the Quick Inventory of Depressive
Symptomatology-Self Report. Eighty-four individuals were included; of these, 30
patients (35.7%) showed psychological dependence on antidepressants (i.e. a total
score of >=5 in the SDS). A multiple regression analysis showed that PDSS scores
and illness duration were correlated positively with SDS total scores. A binary
regression model showed that absence of remission (i.e. a total score of >=5 in
the PDSS) and longer duration of illness increased the risk of dependence on
antidepressants. Approximately one-third of the patients with panic disorder,
receiving antidepressants, fulfilled the criteria for psychological dependence on
these drugs. The results underscore the need for close monitoring, especially for
those who present severe symptomatology or have a chronic course of the illness.
PMID- 27496598
TI - What's New in Shock, Military Supplement September 2016.
PMID- 27496599
TI - The National Trauma Research Repository: Ushering in a New ERA of trauma research
(Commentary).
AB - Despite being the leading cause of death in the United States for individuals 46
years and younger and the primary cause of death among military service members,
trauma care research has been underfunded for the last 50 years. Sustained
federal funding for a coordinated national trauma clinical research program is
required to advance the science of caring for the injured. The Department of
Defense is committed to funding studies with military relevance; therefore, it
cannot fund pediatric or geriatric trauma clinical trials. Currently, trauma
clinical trials are often performed within a single site or a small group of
trauma hospitals, and research data are not available for secondary analysis or
sharing across studies. Data-sharing platforms encourage transfer of research
data and knowledge between civilian and military researchers, reduce redundancy,
and maximize limited research funding. In collaboration with the Department of
Defense, trauma researchers formed the Coalition for National Trauma Research
(CNTR) in 2014 to advance trauma research in a coordinated effort. CNTR's member
organizations are the American Association for the Surgery of Trauma (AAST), the
American College of Surgeons Committee on Trauma (ACS COT), the Eastern
Association for the Surgery of Trauma (EAST), the Western Trauma Association
(WTA), and the National Trauma Institute (NTI). CNTR advocates for sustained
federal funding for a multidisciplinary national trauma research program to be
conducted through a large clinical trials network and a national trauma research
repository. The initial advocacy and research activities underway to accomplish
these goals are presented.
PMID- 27496600
TI - Adult, previously untreated patients remain a significant therapeutic challenge.
PMID- 27496601
TI - Varicella with rapidly progressive hepatitis presenting with multiple hepatic
nodules in a child with acute leukemia.
AB - Abdominal pain may precede the characteristic varicella skin lesions in
immunocompromised patients with visceral varicella. The absence of skin lesions
may delay timely diagnosis and treatment of varicella for those patients.
Furthermore, abdominal imaging findings to provide information to diagnose
visceral varicella have rarely been reported. Varicella was diagnosed in a 5-year
old boy with acute lymphoblastic leukemia complaining of fever and abdominal pain
followed by papulovesicular skin lesions. Later, the patient was found to have
rapidly progressive acute hepatitis, and abdominal computed tomography showed
multiple hypodense hepatic nodules. The patient was treated with intravenous
acyclovir, intravenous immunoglobulin, and empirical antibiotic and antifungal
therapy. However, his fever and abdominal pain persisted, and a laparoscopic
liver biopsy was performed to differentiate other causes of the persisting
symptoms. Eventually, the patient was diagnosed with visceral varicella based on
histopathologic findings. In conclusion, visceral varicella should be considered
in immunocompromised patients with abdominal pain and multiple hypodense hepatic
nodules on abdominal imaging studies. However, bacteria, fungi, and tuberculosis
can produce similar imaging findings; therefore, a biopsy may be necessary in
patients not responding to antiviral therapy.
PMID- 27496602
TI - Risk factors and microbiology of wound infections following cesarean delivery:
Experience of a single institution.
AB - AIMS: To determine the prevalence of wound infection following cesarean delivery,
risk factors, common bacterial pathogens and their antibiotic sensitivity.
MATERIAL-METHOD: The study population consisted of 5787 cesarean deliveries. All
of the patients received 2 g doses of cephazolin perioperatively for antibiotic
prophylaxis. Patients with wound infection who had two doses of 1 g cephazolin
postoperatively and who were continued on oral preparations of 500 mg of
cephuroxime twice daily for 5 days after hospital discharge were included in
Group A. Patients with wound infection whose postoperative antibiotics and
antibiotics after discharge were omitted were included in Group B. Patient
related variables, gestational age, co-morbidities, cesarean section indications,
neonatal intensive care requirements were assessed. Risk factors were evaluated
according to the type of the procedure (elective or emergent) and administered
antibiotic protocol. RESULTS: The incidence of wound infection following cesarean
section was 0,37% in elective operations and 5,4% in emergency cases. On the
other hand, wound infection rate was found to be 1,35% in antibiotic receiving
group (Group A) and 1,12% in the group not receiving antibiotics (Group B).
CONCLUSION: Increased rate of wound infections were remarkable in emergency cases
and postoperative antibiotics did not have a major impact in reducing the rate of
wound infection following cesarean section.
PMID- 27496603
TI - Structure and properties of native and unfolded lysing enzyme from T. harzianum:
Chemical and pH denaturation.
AB - The effect of chemical denaturants and pH on the change of the conformation of
the protein Lysing Enzyme from Trichoderma Harzianum has been investigated by
dynamic light scattering (DLS) and turbidimetry. Chemical denaturants are
frequently used to describe the mechanisms of folding and transition states. We
have analyzed the pH effect on the properties and particle size of the protein.
The compaction factor CI has shown that the protein is weakly disordered. The
molecular dynamics simulations confirm, at neutral pH, that the protein has a low
net charge and high hydrophobicity.
PMID- 27496604
TI - Anomalous diffusion of poly(ethylene oxide) in agarose gels.
AB - We report on the effect of probe size and diffusion time of poly(ethylene) oxide
in agarose gels. Time-dependence of the diffusion coefficient, reflecting
anomalous diffusion, was observed for poly(ethylene) oxide chains with
hydrodynamic radii exceeding about 20nm at an agarose concentration of 2%. The
main conclusion is that the pore distribution includes pores that are only
several nm across, in agreement with scattering reports in the literature.
Interpretation of the diffusion coefficient dependence on the probe size based on
a model of entangled rigid rods yielded a rod length of 72nm.
PMID- 27496605
TI - Enzymatically-gellable galactosylated chitosan: Hydrogel characteristics and
hepatic cell behavior.
AB - The influence of contents of galactose and phenolic hydroxyl (Ph) groups
incorporated into chitosan was investigated on characteristics of the chitosan
derivatives and the resultant gels as well as HepG2 cell attachment and growth
behaviors. Introduction of galactose groups increased the solubility of the
chitosan derivatives. The gelation time decreased with increasing content of Ph
groups in the chitosan derivatives. The increase of galactose groups incorporated
at a fixed content of Ph groups improved mechanical properties of the resultant
gels. In vitro degradation rate of the resultant gels decreased by increasing Ph
groups and decreasing galactose groups incorporated into the chitosan
derivatives. The HepG2 cells formed dense spheroid cell clusters when the
galactose groups were absent or incorporated at high level into chitosan
(13.8mol%). However, the cells exhibited spreading morphology with spheroid
formation on the gels containing 1.1 and 5.2mol% galactose groups. The albumin
secretion level on a cellular basis also increased considerably when the
galactose groups increased to 13.8mol%. The results demonstrated the potential of
the chitosan derivative hydrogels for liver tissue engineering applications.
PMID- 27496607
TI - Localised semicrystalline phases of MaSp1 proteins show high sensitivity to
overshearing in beta-sheet nanocrystals.
AB - We consider the effects of beta-sheet over-shearing on the development of semi
crystallinity in clusters of MaSp1 spider dragline silk proteins. Using molecular
dynamics methods, we find that the extent of crystalline matter in the localised
region of an over-sheared nanocrystal can in fact increase through over-shearing
beta-sheets. This is due to both; the influence of beta-sheets on surrounding
amorphous matter and the influence of amorphous matter in destabilising beta
sheets at their interfaces. In both cases the result is the development of
increased molecular order. Beyond a critical distance of over-shearing,
crystallinity decreases due to a decrease in the stability of both over-sheared
beta-sheets and amorphous matter. Crystallinity of a system as a function of
overshearing of beta-sheets follows a Gaussian form. Larger stacks of
overshearing beta-sheets are energetically more stable than smaller stacks and
are consequently able to develop the highest levels of crystallinity within the
model systems. The elastic moduli computed herein indicate that the most
crystalline oversheared systems are heightened in stiffness through overshearing,
though there is concurrently a decrease in extensibility.
PMID- 27496606
TI - Enhancement of cordyceps polysaccharide production via biosynthetic pathway
analysis in Hirsutella sinensis.
AB - The addition of various sulfates for enhanced cordyceps polysaccharide (CP)
production in submerged cultivation of H. sinensis was investigated, and
manganese sulfate was found the most effective. 2mM of manganese sulfate on 0day
(d) was investigated as the optimal adding condition, and the CP production
reached optimum with 5.33%, increasing by 93.3% compared with the control.
Furthermore, the consumption of three main precursors of CP was studied over
cultivation under two conditions. Intracellular mannose content decreased by
43.1% throughout 6days cultivation, which corresponded to CP accumulation rate
sharply increased from 0 d to 6 d, and mannose was considered as the most
preferred precursor for generating CP. Subsequently, mannose biosynthetic pathway
was constructed and verified for the first time in H. sinensis, which constituted
the important part of CP biosynthesis, and transcriptional levels of the
biosynthetic genes were studied. Transcriptional level of gene cpsA was
significantly up-regulated 5.35-fold and it was a key gene involved both in
mannose and CP biosynthesis. This study demonstrated that manganese sulfate
addition is an efficient and simple way to improve CP production. Transcriptional
analysis based on biosynthetic pathway was helpful to find key genes and better
understand CP biosynthesis.
PMID- 27496608
TI - Alterations of testis-specific promoter methylation in cell-free seminal
deoxyribonucleic acid of idiopathic nonobstructive azoospermic men with different
testicular phenotypes.
AB - OBJECTIVE: To explore the feasibility of quantification of testicular DNA
methylation from cell-free seminal DNA (cfsDNA), and analyze promoter methylation
alterations in men with idiopathic nonobstructive azoospermia (NOA). DESIGN:
Comparison between testicular DNA and paired cfsDNA, and among NOA patients with
different testicular phenotypes. SETTING: Academic research institute and
andrology practice. PATIENT(S): Eighty-eight idiopathic NOA patients with
different testicular phenotypes and 24 normozoospermic men. INTERVENTION(S):
Testicular biopsies and semen analysis. MAIN OUTCOME MEASURE(S): Five testis
specific methylated promoters were selected. Promoter methylation was quantified
using MethyLight in testicular DNA and paired cfsDNA, and the mRNA level was
determined by real-time quantitative polymerase chain reaction. RESULT(S):
Correlations of methylation of the selected five promoters between testicular DNA
and paired cfsDNA were observed; and promoter methylation was negatively related
to the messenger RNA level in testis. The cfsDNA methylation of these promoters
showed different dynamic changes among the subtypes of NOA and normozoospermia.
Among them, CCNA1 and DMRT1 promoter methylation in the hypospermatogenesis group
was higher than in other groups and showed diagnostic potential for the patient
with hypospermatogenesis. CONCLUSION(S): Cell-free seminal DNA could be a novel,
noninvasive biomarker for the detection of testicular epigenetic aberrations.
Epigenetic information in cfsDNA related to spermatogenesis may serve to predict
successful testicular sperm retrieval in NOA patients.
PMID- 27496609
TI - 'False-friend' images on optical coherence tomography angiography: early
choroidal neovascularization or artefact?
PMID- 27496610
TI - Cross-hairs: a scatterplot for meta-analysis in R.
AB - We describe a meta-analytic scatterplot that indicates precision of points for
two variables paired within studies; this is equivalent in form to a 'cross
hairs' plot used to portray specificity and sensitivity in diagnostic testing. At
the user's discretion, the plot also displays boxplots for each of the X and Y
variable distributions, means for each of the variables, and the correlation
between the two. The cross-hairs may be suppressed for dense point clouds. The
program is written in R, so it can be modified by the user and can serve as a
companion to existing meta-analysis programs. Some of the program's novel uses
are described and illustrated with (1) independent effect sizes, (2) dependent
effect sizes, and (3) shrunken estimates. Copyright (c) 2016 John Wiley & Sons,
Ltd.
PMID- 27496611
TI - Re-emergence of syphilis in the biological era.
PMID- 27496612
TI - Interaction of a Novel Chaperone PhLP2A With the Heat Shock Protein Hsp90.
AB - PhLP2 is a small cytosolic protein that belongs to the highly conserved phosducin
like family of proteins. In amniote genomes there are two PhLP2 homologs, PhLP2A
and PhLP2B. It has been shown that mammalian PhLP2A modulates the CCT/TRiC
chaperonin activity during folding of cytoskeletal proteins. In order to better
understand the function of PhLP2A in cellular protein quality control system, in
the present study we have searched for its protein targets. Applying
immunoprecipitation followed by mass spectrometry analysis we have identified
Hsp90 as a partner of PhLP2A. With pull down experiments, we have confirmed this
interaction in protein lysate and using purified proteins we have shown that
PhLP2A interacts directly with Hsp90. Furthermore, the proximity ligation assay
(PLA) performed on mIMCD-3 cells has shown that PhLP2A forms complexes with Hsp90
which are mainly localized in the cytoplasm of these cells. Further analysis has
indicated that the level of PhLP2A increases after heat shock or radicicol
treatment, similarly as the level of Hsp90, and that expression of PhLP2A after
heat shock is regulated at the transcriptional level. Moreover, using recombinant
luciferase we have shown that PhLP2A stabilizes this enzyme in a folding
competent state and prevents its denaturation and aggregation. In addition,
overexpression of PhLP2A in HEK-293 cells leads to increased heat stress
resistance. Altogether, our results have shown that PhLP2A interacts with Hsp90
and exhibits molecular chaperone activity toward denatured proteins. J. Cell.
Biochem. 118: 420-429, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27496613
TI - ABA-dependent inhibition of the ubiquitin proteasome system during germination at
high temperature in Arabidopsis.
AB - During germination, endogenous and environmental factors trigger changes in the
transcriptome, translatome and proteome to break dormancy. In Arabidopsis
thaliana, the ubiquitin proteasome system (UPS) degrades proteins that promote
dormancy to allow germination. While research on the UPS has focused on the
identification of proteasomal substrates, little information is known about the
regulation of its activity. Here we characterized the activity of the UPS during
dormancy release and maintenance by monitoring protein ubiquitination and
degradation of two proteasomal substrates: Suc-LLVY-AMC, a well characterized
synthetic substrate, and FUSCA3 (FUS3), a dormancy-promoting transcription factor
degraded by the 26S proteasome. Our data indicate that proteasome activity and
protein ubiquitination increase during imbibition at optimal temperature (21
degrees C), and are required for seed germination. However, abscisic acid (ABA)
and supraoptimal temperature (32 degrees C) inhibit germination by dampening both
protein ubiquitination and proteasome activity. Inhibition of UPS function by
high temperature is reduced by the ABA biosynthesis inhibitor, fluridone, and in
ABA biosynthetic mutants, suggesting that it is ABA dependent. Accordingly,
inhibition of FUS3 degradation at 32 degrees C is also dependent on ABA. Native
gels show that inhibition of proteasome activity is caused by interference with
the 26S/30S ratio as well as free 19S and 20S levels, impacting the proteasome
degradation cycle. Transfer experiments show that ABA-mediated inhibition of
proteasome activity at 21 degrees C is restricted to the first 2 days of
germination, a time window corresponding to seed sensitivity to environmental and
ABA-mediated growth inhibition. Our data show that ABA and high temperature
inhibit germination under unfavourable growth conditions by repressing the UPS.
PMID- 27496615
TI - An effective strategy to diagnose HIV infection: findings from a national audit
of HIV partner notification outcomes in sexual health and infectious disease
clinics in the UK.
AB - OBJECTIVES: Partner notification (PN) is a key public health intervention in the
control of STIs. Data regarding its clinical effectiveness in the context of HIV
are lacking. We sought to audit HIV PN outcomes across the UK. METHODS: All UK
sexual health and HIV services were invited to participate. Clinical audit
consisted of retrospective case-note review for up to 40 individuals diagnosed
with HIV per site during 2011 (index cases) and a review of PN outcomes for up to
five contacts elicited by PN per index case. RESULTS: 169/221 (76%) clinical
services participated (93% sexual health/HIV services, 7% infectious diseases/HIV
units). Most (97%) delivered PN for HIV. Data were received regarding 2964 index
cases (67% male; 50% heterosexual, 52% white). PN was attempted for 88% of index
cases, and outcomes for 3211 contacts were audited (from an estimated total of
6400): 519 (16%) were found not to be at risk of undiagnosed HIV infection, 1399
(44%) were informed of their risk and had an HIV test, 310 (10%) were informed of
the risk but not known to have tested and 983 (30%) were not informed of their
risk of HIV infection. Of 1399 contacts tested through PN, 293 (21%) were newly
diagnosed with HIV infection. Regular partners were most likely to test positive
(p<0.001). CONCLUSIONS: HIV PN is a highly effective diagnostic strategy. Non
completion of PN thus represents a missed opportunity to diagnose HIV in at-risk
populations. Vigorous efforts should be made to pursue PN to identify people
living with, and at risk of, HIV infection.
PMID- 27496616
TI - Transareolar pulmonary bullectomy for primary spontaneous pneumothorax.
AB - BACKGROUND: Conventional 3-port video-assisted thoracoscopic surgery is the
classic approach for the diagnosis and treatment of primary spontaneous
pneumothorax. Transareolar pulmonary bullectomy rarely has been attempted. This
study aimed to evaluate the feasibility and safety of this novel minimally
invasive technique in managing primary spontaneous pneumothorax. METHODS: From
January 2013 to December 2014, a total of 112 male patients with primary
spontaneous pneumothorax underwent transareolar pulmonary bullectomy by use of a
5-mm thoracoscope. RESULTS: All procedures were performed successfully, with a
mean operating time of 26.5 minutes. The mean length of transareolar incision for
the main operation was 2.0 +/- 0.2 cm, the mean length of incision for the camera
port was 0.6 +/- 0.1 cm, and the mean postoperative cosmetic score was 3.0 +/-
0.8. All patients regained consciousness rapidly after surgery. One hundred seven
patients (95.5%) were discharged on postoperative day 2 or 3, with the remainder
discharged on postoperative day 4 or 5. Postoperative complications were minor.
At 6 months postoperatively, there was no obvious surgical scar on the chest
wall, and no patient complained of postoperative pain. No recurrent symptoms were
observed. One-year follow-up revealed an excellent cosmetic result and degree of
satisfaction. CONCLUSIONS: Transareolar pulmonary bullectomy is a safe and
effective therapeutic procedure for primary spontaneous pneumothorax caused by
pulmonary bullae. The incision is hidden in the areola with excellent cosmetic
effects. This novel procedure shows promise as a treatment of primary spontaneous
pneumothorax.
PMID- 27496614
TI - Design and cellular studies of a carbon nanotube-based delivery system for a
hybrid platinum-acridine anticancer agent.
AB - A three-component drug-delivery system has been developed consisting of multi
walled carbon nanotubes (MWCNTs) coated with a non-classical platinum
chemotherapeutic agent ([PtCl(NH3)2(L)]Cl (P3A1; L=N-(2-(acridin-9-ylamino)ethyl)
N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N
[amino(polyethylene glycol)-5000] (DSPE-mPEG). The optimized P3A1-MWCNTs are
colloidally stable in physiological solution and deliver more P3A1 into breast
cancer cells than treatment with the free drug. Furthermore, P3A1-MWCNTs are
cytotoxic to several cell models of breast cancer and induce S-phase cell cycle
arrest and non-apoptotic cell death in breast cancer cells. By contrast, free
P3A1 induces apoptosis and allows progression to G2/M phase. Photothermal
activation of P3A1-MWCNTs to generate mild hyperthermia potentiates their
cytotoxicity. These findings suggest that delivery of P3A1 to cancer cells using
MWCNTs as a drug carrier may be beneficial for combination cancer chemotherapy
and photothermal therapy.
PMID- 27496618
TI - The left atrial appendage: Won't get fooled again.
PMID- 27496617
TI - Off-pump versus on-pump coronary artery bypass surgery in patients with actively
treated diabetes and multivessel coronary disease.
AB - OBJECTIVES: We conducted a single-center analysis on short-term outcomes and long
term survival in actively treated diabetic patients undergoing off-pump coronary
artery bypass versus on-pump coronary artery bypass surgery. METHODS: The final
population consisted of 2450 patients with actively treated diabetes (mean age,
66 +/- 9 years; female/male 545/1905, 22%). Of those, 1493 subjects were orally
treated and 1011 subjects were taking insulin. Off-pump coronary artery bypass
and on-pump coronary artery bypass were performed in 1253 and 1197 patients,
respectively. Propensity score matching was used to compare the 2 matched groups.
RESULTS: When compared with on-pump coronary artery bypass, off-pump coronary
artery bypass was associated with a significant risk reduction for postoperative
cerebrovascular accident (odds ratio, 0.49; 95% confidence interval [CI], 0.25
0.99; P = .04), need for postoperative intra-aortic balloon pump (odds ratio,
0.48; 95% CI, 0.30-0.77; P = .002), and reexploration for bleeding (odds ratio,
0.55; 95% CI, 0.33-0.94; P = .02). Off-pump coronary artery bypass did not
significantly affect early (hazard ratio [HR], 1.32; 95% CI, 0.73-2.40; P = .36)
and late (HR, 1.08; 95% CI, 0.92-1.28; P = .32) mortality. However, off-pump
coronary artery bypass with incomplete revascularization was associated with
reduced survival when compared with off-pump coronary artery bypass with complete
revascularization (HR, 1.82; 95% CI, 1.34-2.46; P = .0002) and on-pump coronary
artery bypass with complete revascularization (HR, 1.83; 95% CI, 1.36-2.47; P <
.0001). CONCLUSIONS: Off-pump coronary artery bypass is a safe and feasible
option for diabetic patients with multivessel disease, reduces the incidence of
early complications including postoperative cerebrovascular events, and provides
excellent long-term survival similar to on-pump coronary artery bypass surgery in
case of complete revascularization.
PMID- 27496619
TI - Functionalization of Hydrogenated Graphene: Transition-Metal-Catalyzed Cross
Coupling Reactions of Allylic C-H Bonds.
AB - The chemical functionalization of hydrogenated graphene can modify its physical
properties and lead to better processability. Herein, we describe the chemical
functionalization of hydrogenated graphene through a dehydrogenative cross
coupling reaction between an allylic C-H bond and the alpha-C-H bond of
tetrahydrothiophen-3-one using Cu(OTf)2 as the catalyst and DDQ as the oxidant.
The chemical functionalization was confirmed by X-ray photoelectron spectroscopy
and Fourier transform infrared spectroscopy and visualized by scanning electron
microscopy. The functionalized hydrogenated graphene material demonstrated
improved dispersion stability in water, bringing new quality to the elusive
hydrogenated graphene (graphane) materials. Hydrogenated graphene provides broad
possibilities for chemical modifications owing to its reactivity.
PMID- 27496620
TI - Bayesian spatial analysis of the surgical incidence rate of human cystic
echinococcosis in north-eastern Iran.
AB - BACKGROUND: Cystic echinococcosis (CE) is a zoonotic disease that presents a
public health challenge and a socioeconomic burden on developing areas in the
Middle East. This study used spatial methods to assess the distribution of
surgically managed CE cases in an endemic region of north-eastern Iran. METHODS:
For the years 2001-2007, a case series of all 446 patients that were surgically
treated for CE in a referral hospital in north-eastern Iran was evaluated.
Patients seen at the referral hospital represent 35 counties in three provinces
(Razavi Khorasan, North Khorasan, and South Khorasan). A Besag, York and Mollie
(BYM) spatial model was used to produce smoothed standardized incidence ratios
(SIRs) for surgically managed cases of CE for the 35 counties represented in this
study. RESULTS: Out of 446 surgically managed patients, 54% were male. County
level crude incidence rates ranged from 0 to 3.27 cases per 100,000 population.
The highest smoothed SIR (3.46) was for Sarakhs County in the province of Razavi
Khorasan, while the lowest smoothed SIR (0.05) was for Birjand County, located in
the province of South Khorasan. CONCLUSION: SIRs for CE were highest for the
province of Razavi Khorasan, which has large ranching and agricultural
industries. Additional studies are needed to better evaluate the role of climate,
land cover, and livestock rearing on local Echinococcus granulosus transmission
in Iran.
PMID- 27496621
TI - Detection of wild animals as carriers of Leptospira by PCR in the Pantanal biome,
Brazil.
AB - Leptospiral infection is widespread in wildlife. In this context, wild ecosystems
in tropical countries hold a vast biodiversity, including several species that
may act as potential reservoirs of leptospires. The Pantanal biome presents
highly favorable environmental conditions for the occurrence of leptospirosis,
such as high temperatures, constant flooding, and high biodiversity. The purpose
of this study was to detect wild animals as carriers of Leptospira sp. using
direct methods (PCR and culture) in the Pantanal biome, Brazil. A total of 35
animals were studied, namely Cerdocyon thous, Nasua nasua, Ozotoceros
bezoarticus, and Sus scrofa species. Blood for serology (MAT) and urine for
bacteriological culturing and PCR was sampled. The most prevalent serogroups were
Javanica and Djasiman. Additionally, 40.6% of these animals presented PCR
positive reactions. Seroreactivity associated with the high frequency of
leptospiral carriers among the different studied species suggests a high level of
exposure of the studied animals to pathogenic Leptospira strains. Our results are
still limited and the actual role of the studied animals in the epidemiology of
leptospirosis in the Pantanal region remains to be elucidated.
PMID- 27496622
TI - Cutaneous leishmaniasis prevalence and morbidity based on environmental factors
in Ilam, Iran: Spatial analysis and land use regression models.
AB - The aim of this study was to investigate the impact of the environmental factors
on cutaneous leishmaniasis (CL) prevalence and morbidity in Ilam province,
western Iran, as a known endemic area for this disease. Accurate locations of
3237 CL patients diagnosed from 2013 to 2015, their demographic information, and
data of 17 potentially predictive environmental variables (PPEVs) were prepared
to be used in Geographic Information System (GIS) and Land-Use Regression (LUR)
analysis. The prevalence, risk, and predictive risk maps were provided using
Inverse Distance Weighting (IDW) model in GIS software. Regression analysis was
used to determine how environmental variables affect on CL prevalence. All maps
and regression models were developed based on the annual and three-year average
of the CL prevalence. The results showed that there was statistically significant
relationship (P value<=0.05) between CL prevalence and 11 (64%) PPEVs which were
elevation, population, rainfall, temperature, urban land use, poorland, dry
farming, inceptisol and aridisol soils, and forest and irrigated lands. The
highest probability of the CL prevalence was predicted in the west of the study
area and frontier with Iraq. An inverse relationship was found between CL
prevalence and environmental factors, including elevation, covering soil,
rainfall, agricultural irrigation, and elevation while this relation was positive
for temperature, urban land use, and population density. Environmental factors
were found to be an important predictive variables for CL prevalence and should
be considered in management strategies for CL control.
PMID- 27496623
TI - Radiation dermatitis: an overview.
AB - Radiation therapy has been a commonly employed modality for a variety of
ailments, including cancer. Patients undergoing radiation often experience acute
and/or chronic skin changes that can be detrimental to their quality of life.
Many topical agents and specialized wound dressings are being used for the
prevention and management of radiation-induced skin changes. However, no single
therapeutic option has been found to be consistently effective.
PMID- 27496624
TI - The effects of gliclazide, methylcobalamin, and gliclazide+methylcobalamin
combination therapy on diabetic peripheral neuropathy in rats.
AB - AIMS: This study investigated the efficacies of gliclazide (GLZ), methylcobalamin
(MCA), and GLZ+MCA combination therapy on DPN by evaluating the treatment-related
changes in peripheral nerve function, the polyol pathway, and oxidative stress in
the sciatic nerve of streptozotocin-induced diabetic rats. MATERIALS AND METHODS:
The rat model of streptozotocin-induced diabetes was orally given GLZ
(25mg/kg/day), MCA (175MUg/kg/day), and GLZ+MCA (25mg/kg/day+175MUg/kg/day)
combination therapy for 8weeks, in order to observe its effects on the motor
nerve conduction velocity (MNCV), on the activities of Na(+), K(+)-ATPase, aldose
reductase(AR), AR mRNA expression, on the polyol contents, antioxidative enzyme
activities and peroxidation products in the sciatic never tissue. KEY FINDINGS:
Most of the indicators of DPN, such as delayed MNCV, altered/damaged nerve
structure, inhibited Na(+),K(+)-ATPase activity, enhanced AR activity and AR mRNA
expression, increased polyol contents, altered Cu,Zn-superoxide dismutase,
catalase, and glutathione-peroxidase activities, and elevated malondialdehyde
level in the sciatic nerves of the diabetic rats, were significantly ameliorated
by treatment with either GLZ or MCA. Moreover, the combination of GLZ and MCA was
found to enhance the curative effect on DPN in parts of above-mentioned
parameters as compared to monotherapy. SIGNIFICANCE: Monotherapy with GLZ or MCA,
and especially the combined application of GLZ and MCA, could be efficient
therapeutic strategies for combating experimental DPN in diabetic rats.
PMID- 27496625
TI - Are community level prescription opioid overdoses associated with child harm? A
spatial analysis of California zip codes, 2001-2011.
AB - BACKGROUND: Non-medical prescription opioid use is increasing globally within
high-income countries, particularly the United States. However, little is known
about whether it is associated with negative outcomes for children. In this
study, we use prescription opioid overdose as a proxy measure for non-medical
prescription opioid use and ask the following: Do California communities with
greater rates of non-medical prescription opioid use also have higher rates of
child maltreatment and unintentional child injury? METHODS: We used longitudinal
population data to examine ecological associations between hospital discharges
involving overdose of prescription opioids and those for child maltreatment or
child injury in California zip codes between 2001 and 2011 (n=18,517 zip-code
year units) using Bayesian space-time misalignment models. RESULTS: The
percentage of hospital discharges involving prescription opioid overdose was
positively associated with the number of hospital discharges for child
maltreatment (relative rate=1.089, 95% credible interval (1.004, 1.165)) and
child injury (relative rate=1.055, 95% credible interval (1.012, 1.096)) over the
ten-year period, controlling for other substance use and environmental factors.
CONCLUSIONS: Increases in community level prescription opioid overdoses between
2001 and 2011 are associated with a 2.06% increase in child maltreatment
discharges and a 1.27% increase in discharges for child injury. Communities with
higher rates of non-medical prescription opioid use may experience greater levels
of child harms.
PMID- 27496626
TI - Systemic-Pulmonary Shunt Facilitates the Growth of the Pulmonary Valve Annulus in
Patients With Tetralogy of Fallot.
AB - BACKGROUND: Transannular patching (TAP) frequently accompanies primary repairs
(PRs) in symptomatic neonates with tetralogy of Fallot (TOF). If a systemic
pulmonary shunt (SPS) facilitates the growth of the pulmonary valve annulus
(PVA), patients with a marginally small PVA could benefit from a staged repair in
terms of lowering the risk of TAP. METHODS: Among 216 infants with TOF who
underwent surgical intervention between January 2004 and December 2013, 29
infants underwent SPS with a subsequent repair (SPS group), whereas 187 infants
received a PR (PR group). Median age and the Z-score of the PVA (PVA [Z]) at SPS
were 32 days and -3.5, respectively. There was one late death and one follow-up
loss after SPS, and preservation of the PVA was achieved on repair in 16 patients
(16 of 29; 55%). RESULTS: Multiple regression analysis showed that performance of
SPS was the only indicator of the increase in the PVA (Z) in the entire cohort (n
= 216). On mixed linear regression, the PVA (Z) increased significantly after the
placement of an SPS (-3.6 + 0.2*duration in months, p = 0.001), whereas the
prerepair changes in the PVA (Z) were not statistically significant in the PR
group (p = 0.7), with a significant intergroup difference (p < 0.001). Receiver
operating characteristic curve analysis showed that placement of TAP is expected
when the preshunt PVA (Z) is smaller than -4.2 (area under the curve: 0.82; 95%
confidence interval: 0.62 to 1.00; sensitivity, 100%; specificity, 73%).
CONCLUSIONS: SPS facilitates outgrowth of the PVA over somatic growth in patients
with TOF. However, preservation of the PVA may not be achieved on staged repair
if the initial PVA is too small.
PMID- 27496627
TI - Minimally Invasive Peratrial Device Closure of Perimembranous Ventricular Septal
Defect Through a Right Infraaxillary Route: Clinical Experience and Preliminary
Results.
AB - BACKGROUND: Both percutaneous and perventricular device closures of
perimembranous ventricular septal defects (PmVSD) present certain drawbacks. We
report our experiences with a new, minimally invasive surgery using a peratrial
device closure of PmVSD through a right infraaxillary route. METHODS: Between
January 2014 and October 2015, 145 patients (71 male, 74 female) with PmVSD, aged
0.5 to 9.7 years (mean 2.8 +/- 2.2) and weighing between 6.1 kg and 43 kg (mean
14.0 +/- 6.6 kg) were included in this study. In patients with left lateral
position, a 2- to 3-cm incision was made along the right midaxillary line. The
thoracic cavity was entered through the fourth intercostal space. With the help
of transesophageal echocardiography guidance, a specially designed hollow probe
was inserted into the right atrium. The probe was passed through the tricuspid
valve into the right ventricle. The tip of the probe was adjusted to point to or
cross the defect. A flexible guidewire was inserted into the left ventricle
through the channel of the probe to establish a delivery pathway. Then, the
device was deployed to close the defect. RESULTS: A total of 142 cases (97.9%)
were successfully occluded, whereas 3 cases failed and were converted to
cardiopulmonary bypass operation through the original incision. The device size
ranged from 4.0 to 10.0 mm (mean 5.1 +/- 1.4 mm), and all devices were
concentric. Follow-up in all patients ranged from 1.0 to 22.8 months (mean 9.9 +/
5.6) and revealed no evident valve regurgitation, no complete atrioventricular
block, and no device dislocation. CONCLUSIONS: This new minimally invasive
technique of peratrial device closure through a right infraaxillary route under
transesophageal echocardiography guidance was shown to be a safe, effective,
feasible, and cosmetically superior treatment for PmVSD.
PMID- 27496628
TI - Impact of Operative and Postoperative Factors on Neurodevelopmental Outcomes
After Cardiac Operations.
AB - BACKGROUND: Neurodevelopmental disability is common after operations for
congenital heart defects. We previously showed that patient and preoperative
factors, center, and calendar year of birth explained less than 30% of the
variance for the Psychomotor Development Index (PDI) and the Mental Development
Index (MDI) of the Bayley Scales of Infant Development-Second Edition. Here we
investigate how much additional variance in PDI and MDI is contributed by
operative variables and postoperative events. METHODS: We analyzed
neurodevelopmental outcomes after operations with cardiopulmonary bypass at age 9
months or younger between 1996 and 2009. We used linear regression to investigate
the effect of operative factors (age, weight, and cardiopulmonary bypass
variables) and postoperative events on neurodevelopmental outcomes, adjusting for
center, type of congenital heart defect, year of birth, and preoperative factors.
RESULTS: We analyzed 1,770 children from 22 institutions with neurodevelopmental
testing at age 13.3 months (range, 6 to 30 months). Among operative factors,
longer total support time was associated with lower PDI and MDI (p < 0.05). When
postoperative events were added, use of either extracorporeal membrane
oxygenation or ventricular assist device support, and longer postoperative length
of stay were associated with lower PDI and MDI (p < 0.05). Longer total support
time was not a significant predictor in these models. After adjusting for
patient, preoperative, intraoperative, and postoperative factors, measured
intraoperative and postoperative factors accounted for 5% of the variances in PDI
and MDI. CONCLUSIONS: Operative factors may be less important than innate patient
and preoperative factors and postoperative events in predicting early
neurodevelopmental outcomes after cardiac operations in infants.
Neurodevelopmental outcomes improved over calendar time when adjusted for patient
and medical variables.
PMID- 27496629
TI - Resting End-Tidal Carbon Dioxide Predicts Respiratory Complications in Patients
Undergoing Thoracic Surgical Procedures.
AB - BACKGROUND: Ventilatory efficiency (Ve/Vco2 slope [minute ventilation to carbon
dioxide output slope]) has been shown to predict morbidity and mortality in lung
resection candidates. Patients with increased Ve/Vco2 during exercise also
exhibit an increased Ve/Vco2 ratio and a decreased end-tidal CO2 at rest. This
study hypothesized that ventilatory values at rest predict respiratory
complications and death in patients undergoing thoracic surgical procedures.
METHODS: Inclusion criteria for this retrospective, multicenter study were
thoracotomy and cardiopulmonary exercise testing as part of routine preoperative
assessment. Respiratory complications were assessed from the medical records
(from the hospital stay or from the first 30 postoperative days). For
comparisons, Student's t test or the Mann-Whitney U test was used. Logistic
regression and receiver operating characteristic analyses were performed for
evaluation of measurements associated with respiratory complications. Data are
summarized as mean +/- SD; p <0.05 is considered significant. RESULTS: Seventy
six subjects were studied. Postoperatively, respiratory complications developed
in 56 (74%) patients. Patients with postoperative respiratory complications had
significantly lower resting tidal volume (0.8 +/- 0.3 vs 0.9 +/- 0.3L; p = 0.03),
lower rest end-tidal CO2 (28.1 +/- 4.3vs 31.5 +/- 4.2 mm Hg; p < 0.01), higher
resting Ve/Vco2 ratio (45.1 +/- 7.1 vs 41.0 +/- 6.4; p = 0.02), and higher
Ve/Vco2 slope (34.9 +/- 6.4 vs 31.2 +/- 4.3; p = 0.01). Logistic regression (age
and sex adjusted) showed resting end-tidal CO2 to be the best predictor of
respiratory complications (odds ratio: 1.21; 95% confidence interval: 1.06 to
1.39; area under the curve: 0.77; p = 0.01). CONCLUSIONS: Resting end-tidal CO2
may identify patients at increased risk for postoperative respiratory
complications of thoracic surgical procedures.
PMID- 27496630
TI - Outcomes Using a Conservative Versus Liberal Red Blood Cell Transfusion Strategy
in Infants Requiring Cardiac Operation.
AB - BACKGROUND: The optimal hemoglobin for infants after cardiac operation is
unknown. Red blood cells (RBCs) are commonly transfused to maintain high
hemoglobin concentrations in the absence of a clinical indication. We
hypothesized that infants can be managed with a postoperative conservative RBC
transfusion strategy, resulting in lower daily hemoglobin concentrations, without
evidence of impaired oxygen delivery (ie, lactate, arteriovenous oxygen
difference [avO2diff]), or adverse clinical outcomes. METHODS: Infants weighing
10 kg or less undergoing biventricular repair or palliative (nonseptated)
operation were randomly assigned to either a postoperative conservative or
liberal transfusion strategy. Conservative group strategy was RBC transfusion for
a hemoglobin less than 7.0 g/dL for biventricular repairs or less than 9.0 g/dL
for palliative procedures plus a clinical indication. Liberal group strategy was
RBC transfusion for hemoglobin less than 9.5 g/dL for biventricular repairs or
less than 12 g/dL for palliative procedures regardless of clinical indication.
RESULTS: After the operation of 162 infants (82 conservative [53 biventricular,
29 palliative], 80 liberal [52 biventricular, 28 palliative]), including 12
Norwood procedures (6 conservative, 6 liberal), daily hemoglobin concentrations
were significantly lower within the conservative group than the liberal group by
postoperative day 1 and remained lower for more than 10 days. The percentage of
patients requiring a RBC transfusion, number of transfusions, and volume of
transfusions were all significantly lower within the conservative group. Despite
lower hemoglobin concentrations within the conservative group, lactate, avO2diff,
and clinical outcomes were similar. CONCLUSIONS: Infants undergoing cardiac
operation can be managed with a conservative RBC transfusion strategy. Clinical
indications should help guide the decision for RBC transfusion even in this
uniquely vulnerable population. Larger multicenter trials are needed to confirm
these results, and focus on the highest risk patients would be of great interest.
PMID- 27496631
TI - Early and Midterm Clinical and Hemodynamic Outcomes of Transcatheter Valve-in
Valve Implantation: Results From a Multicenter Experience.
AB - BACKGROUND: Transcatheter valve-in-valve (VIV) implantation is an alternative
option in inoperable or high-risk patients with prosthetic valve dysfunction. Aim
of this retrospective multicenter study was to evaluate early and midterm
clinical and hemodynamic outcomes of patients undergoing aortic (VIV-A) and
mitral VIV (VIV-M). METHODS: We analyzed data of 66 procedures performed in 65
patients who underwent VIV procedures in the VIV-A and VIV-M position at 5
Italian institutions from January 2008 to May 2015. VIV-A and VIV-M were 44 (68%)
and 22 (32%), respectively; 1 patient underwent combined mitroaortic VIV. Study
devices were both balloon-expandable and self-expandable. Outcomes were defined
according to the updated Valve Academic Research Consortium definitions. RESULTS:
Overall all-cause 30-day mortality was 6% (4 patients), and it was 4.5% and 9% in
VIV-A and VIV-M, respectively (2 patients in each group). Mean follow-up was 14
+/- 14 months. Kaplan-Meier survival of the entire cohort at 1, 2, 3, and 4 years
was 84.4% +/- 4.9%, 80.5% +/- 6%, 74.3 +/- 8.1%, and 62% +/- 13.2%, respectively.
Age (hazard ratio: 1.1; 95% confidence interval: 1.0 to 1.3; p = 0.035) and
diabetes (hazard ratio: 7.2, 95% confidence interval: 2.1 to 23.7; p = 0.001)
were identified as independent predictors of mortality. Degenerated surgical
aortic prostheses with an internal diameter (ID) less than 20 mm had
significantly higher gradients if compared to prostheses with ID 21 to 23 mm and
greater than 23 mm. After VIV-A, a severe stenosis (mean gradient greater than 35
mm Hg) was detected in 3 (6.8%) cases, all with ID less than 20 mm. CONCLUSIONS:
VIV provides good early and midterm results in high-risk or inoperable patients
with mitral or aortic bioprosthesis dysfunction. Age and diabetes are
independently associated with mortality. Size of bioprosthesis ID has a
significant impact on postoperative gradients.
PMID- 27496632
TI - Red eye after strabismus surgery: community-acquired MRSA periocular infection.
PMID- 27496633
TI - Growth inhibition in a brain metastasis model by antibody delivery using focused
ultrasound-mediated blood-brain barrier disruption.
AB - HER2-targeting antibodies (i.e. trastuzumab and pertuzumab) prolong survival in
HER2-positive breast cancer patients with extracranial metastases. However, the
response of brain metastases to these drugs is poor, and it is hypothesized that
the blood-brain barrier (BBB) limits drug delivery to the brain. We investigated
whether we could improve the response by temporary disruption of the BBB using
focused ultrasound in combination with microbubbles. To study this, we inoculated
30 nude rats with HER2-positive cells derived from a brain metastasis of a breast
cancer patient (MDA-MB-361). The animals were divided into three groups: a
control-group that received no treatment; an antibody-only group that received
six weekly treatments of trastuzumab and pertuzumab; and an ultrasound+antibody
group that received trastuzumab and pertuzumab in combination with six weekly
sessions of BBB disruption using focused ultrasound. In two animals, the
leakiness of the tumors before disruption was evaluated using contrast-enhanced
T1-weighted magnetic resonance imaging and found that the tumors were not leaky.
The same technique was used to evaluate the effectiveness of BBB disruption,
which was successful in all sessions. The tumor in the control animals grew
exponentially with a growth constant of 0.042+/-0.011mm(3)/day. None of the
antibody-only animals responded to the treatment and the growth constant was
0.033+/-0.009mm(3)/day during the treatment period. Four of the ten animals in
the ultrasound+antibody-group showed a response to the treatment with an average
growth constant of 0.010+/-0.007mm(3)/day, compared to a growth constant 0.043+/
0.013mm(3)/day for the six non-responders. After the treatment period, the tumors
in all groups grew at similar rates. As the tumors were not leaky before BBB
disruption and there were no responders in the antibody-only group, these results
show that at least in some cases disruption of the BBB is necessary for a
response to the antibodies in these brain metastases. Interestingly, only some of
the rats responded to the treatment. We did not observe a difference in tumor
volume at the start of the treatment, nor in HER2 expression or in contrast
enhancement on MRI between the responders and non-responders to explain this.
Better understanding of why certain animals respond is needed and will help in
translating this technique to the clinic. In conclusion, we demonstrate that BBB
disruption using focused ultrasound in combination with antibody therapy can
inhibit growth of breast cancer brain metastasis.
PMID- 27496634
TI - Repeated fractional intradermal dosing of an inactivated polio vaccine by a
single hollow microneedle leads to superior immune responses.
AB - The purpose of this study was to investigate the effect of various repeated
fractional intradermal dosing schedules of inactivated polio vaccine serotype 1
(IPV1) on IPV1-specific IgG responses in rats. By utilizing an applicator that
allowed for precisely controlled intradermal microinjections by using a single
hollow microneedle, rats were immunized intradermally with 5 D-antigen units (DU)
of IPV1 at 150MUm skin depth. This dose was administered as a bolus, or in a
repeated fractional dosing schedule: 4 doses of 1.25 DU (1/4th of total dose)
were administered on four consecutive days or every other day; 8 doses of 0.625
DU (1/8th of total dose) were administered on eight consecutive days; or 4
exponentially increasing doses (0.04, 0.16, 0.8 and 4 DU), either with or without
an exponentially increasing CpG oligodeoxynucleotide 1826 (CpG) dose, were
administered on four consecutive days. All of these fractional dosing schedules
resulted in up to ca. 10-fold higher IPV1-specific IgG responses than intradermal
and intramuscular bolus dosing. IPV1 combined with adjuvant CpG in exponential
dosing did not significantly increase the IPV1-specific IgG responses further,
which demonstrated that maximal responses were achieved by fractional dosing. In
conclusion, repeated fractional intradermal IPV1 dosing leads to superior IPV1
specific IgG responses without the use of adjuvants. These results indicate that
a controlled release delivery system for intradermal IPV1 delivery can potentiate
IPV1-specific IgG responses.
PMID- 27496635
TI - Nematode parasite diversity in birds: the role of host ecology, life history and
migration.
AB - Previous studies have found that migratory birds generally have a more diverse
array of pathogens such as parasites, as well as higher intensities of infection.
However, it is not clear whether this is driven by the metabolic and
physiological demands of migration, differential selection on host life-history
traits or basic ecological differences between migratory and non-migratory
species. Parasitic helminths can cause significant pathology in their hosts, and
many are trophically transmitted such that host diet and habitat use play key
roles in the acquisition of infections. Given the concurrent changes in avian
habitats and migratory behaviour, it is critical to understand the degree to
which host ecology influences their parasite communities. We examined nematode
parasite diversity in 153 species of Anseriformes (water birds) and
Accipitriformes (predatory birds) in relation to their migratory behaviour, diet,
habitat use, geographic distribution and life history using previously published
data. Overall, migrators, host species with wide geographic distributions and
those utilizing multiple aquatic habitats had greater nematode richness (number
of species), and birds with large clutches harboured more diverse nematode fauna
with respect to number of superfamilies. Separate analyses for each host order
found similar results related to distribution, habitat use and migration;
however, herbivorous water birds played host to a less diverse nematode community
compared to those that consume some animals. Birds using multiple aquatic
habitats have a more diverse nematode fauna relative to primarily terrestrial
species, likely because there is greater opportunity for contact with parasite
infectious stages and/or consumption of infected hosts. As such, omnivorous and
carnivorous birds using aquatic habitats may be more affected by environmental
changes that alter their diet and range. Even though there were no overall
differences in their ecology and life history compared with non-migrators,
migratory bird species still harboured a more diverse array of nematodes,
suggesting that this behaviour places unique demands on these hosts and warrants
further study.
PMID- 27496636
TI - Disruption of host-seeking behaviour by the salmon louse, Lepeophtheirus
salmonis, using botanically derived repellents.
AB - The potential for developing botanically derived natural products as novel feed
through repellents for disrupting settlement of the salmon louse, Lepeophtheirus
salmonis (Caligidae) upon farmed Atlantic salmon, Salmo salar, was investigated
using an established laboratory vertical Y-tube behavioural bioassay for
assessing copepodid behaviour. Responses to artificial sea water conditioned with
the odour of salmon, or to the known salmon-derived kairomone component, alpha
isophorone, in admixture with selected botanical materials previously known to
interfere with invertebrate arthropod host location were recorded. Materials
included oils extracted from garlic, Allium sativum (Amaryllidaceae), rosemary,
Rosmarinus officinalis (Lamiaceae), lavender, Lavandula angustifolia (Lamiaceae),
and bog myrtle, Myrica gale (Myricaceae), and individual components (diallyl
sulphide and diallyl disulphide from garlic; allyl, propyl, butyl, 4-pentenyl and
2-phenylethyl isothiocyanate from plants in the Brassica genus). Removal of
attraction to salmon-conditioned water (SCW) or alpha-isophorone was observed
when listed materials were presented at extremely low parts per trillion (ppt),
that is picograms per litre or 10-12 level. Significant masking of attraction to
SCW was observed at a level of 10 ppt for diallyl disulphide and diallyl
sulphide, and allyl isothiocyanate and butyl isothiocyanate. The potential of
very low concentrations of masking compounds to disrupt Le. salmonis copepodid
settlement on a host fish has been demonstrated in vitro.
PMID- 27496637
TI - Direct Transcatheter Heart Valve Implantation Versus Implantation With Balloon
Predilatation: Insights From the Brazilian Transcatheter Aortic Valve Replacement
Registry.
AB - BACKGROUND: Direct transcatheter aortic valve replacement (TAVR) is regarded as
having potential advantages over TAVR with balloon aortic valve predilatation
(BAVP) in reducing procedural complications, but there are few data to support
this approach. METHODS AND RESULTS: Patients included in the Brazilian TAVR
registry with CoreValve and Sapien-XT prosthesis were compared according to the
implantation technique, with or without BAVP. Clinical and echocardiographic data
were analyzed in overall population and after propensity score matching. A total
of 761 consecutive patients (BAVP=372; direct-TAVR=389) were included. Direct
TAVR was possible in 99% of patients, whereas device success was similar between
groups (BAVP=81.2% versus direct-TAVR=78.1%; P=0.3). No differences in clinical
outcomes at 30 days and 1 year were observed, including all-cause mortality (7.6%
versus 10%; P=0.25 and 18.1% versus 24.5%; P=0.07, respectively) and stroke (2.8%
versus 3.8%; P=0.85 and 5.5% versus 6.8%; P=0.56, respectively). Nonetheless,
TAVR with BAVP was associated with a higher rate of new onset persistent left
bundle branch block with the CoreValve (47.7% versus 35.1%; P=0.01 at 1 year).
Mean gradient and incidence of moderate/severe aortic regurgitation were similar
in both groups at 1 year (11% versus 13.3%; P=0.57 and 9.8+/-5.5 versus 8.7+/
4.3; P=0.09, respectively). After propensity score matching analysis, all-cause
mortality and stroke remained similar. By multivariable analysis, BAVP and the
use of CoreValve were independent predictors of new onset persistent left bundle
branch block. CONCLUSIONS: The 2 TAVR strategies, with or without BAVP, provided
similar clinical and echocardiographic outcomes over a midterm follow-up although
BAVP was associated with a higher rate of new onset persistent left bundle branch
block, particularly in patients receiving a CoreValve.
PMID- 27496638
TI - Fungal Obstruction of Transcatheter Aortic Valve Replacement Valve.
PMID- 27496639
TI - Allogeneic stem cell transplantation for sickle cell disease.
AB - PURPOSE OF REVIEW: As the safety and availability of allogeneic hematopoietic
stem cell transplantation (HSCT) have improved, this procedure is becoming a
viable option for nonmalignant conditions such as sickle cell disease (SCD).
There are very few treatment options available for SCD, and even with optimal
care SCD patients still suffer from a myriad of comorbidities to multiple organ
systems and have a decreased life span. In this review, we will summarize results
from trials of HSCT for children or adults with SCD using a variety of graft
sources as well as conditioning and graft-versus-host disease prophylaxis
regimens, and discuss the unique challenges that arise in these patients. RECENT
FINDINGS: AlloHSCT for SCD has been performed on small numbers of patients at
multiple centers around the world using several different transplant platforms,
and early outcomes are encouraging. Overall survival is excellent, although graft
failure remains a challenge. SUMMARY: As alloHSCT becomes safer and more widely
available, the procedure should be considered for patients with severe disease
phenotypes in whom the potential benefits of transplantation outweigh the
complications from the disease. AlloHSCT has been shown to reverse or at least
halt the progression of end-organ damage secondary to SCD. More research is
needed to understand the mechanisms underlying graft failure in SCD recipients,
as well as to understand the biopsychosocial underpinnings of persistent pain in
the posttransplant period to maximize the benefit from the transplant procedure.
PMID- 27496640
TI - [Parental perception of their involvement in the care of their children in French
neonatal units].
AB - BACKGROUND: The experience of becoming the parent of a sick or premature newborn
can be particularly distressing for parents. They often encounter challenges to
the development of their parenting roles. Perception of the hospital stay has
never been analyzed on a large scale. OBJECTIVE: To analyze parents' perception
of their involvement in the care of their newborn. METHODS: An internet-based
survey started in France in February 2014 on the basis of a validated
questionnaire composed of 222 neonatal care-related items. A quantitative and
qualitative analysis was performed on the items dealing with parents' involvement
until August 2014. RESULTS: The survey was completed by 1500 parents, 98 % of
whom were mothers. The infants had a mean GA of 32 weeks and a mean birth weight
of 1600g. Parents rated their first care of their infant with mixed emotions
(joy, stress, etc.). Parents were willing to practice new skills through guided
participation, even for more complex care. Skin-to-skin care was only proposed
after 7 days for 20 % of the parents; 10 % of the parents did not feel secure
during this practice. The need for privacy and professional guidance was
essential for meaningful skin-to-skin contact. DISCUSSION: Parents' perception of
participating actively in their infant's care was positive and they felt guided
by the nursing team. Most of them would have been more active with guidance. Skin
to-skin care was appreciated and desired, but could become stressful if the
conditions were not optimal.
PMID- 27496641
TI - Exendin-4 inhibits growth and augments apoptosis of ovarian cancer cells.
AB - Glucagon-like peptide (GLP)-1 promotes proliferation and survival in beta-cell;
however, whether GLP-1 receptor agonists promote growth of human ovarian cancer
cells remain unknown. We aimed to explore the effects of GLP-1 agents on ovarian
cancer cells. GLP-1 receptor expression in human ovarian cancer tissues was
detected by immunohistochemical analysis. The effects of exendin-4, a GLP-1R
agonist, were investigated on proliferation, migration and invasion, apoptosis in
vitro and tumor formation in nude mice of ovarian cancer cells. Our study
demonstrated that GLP-1R expressed in both human ovarian cancer tissues and cell
lines. Exendin-4 inhibited growth, migration and invasion and enhanced apoptosis
of ovarian cancer cells through inhibition of the PI3K/Akt pathway. And exendin-4
attenuated tumor formation by ovarian cancer cells in vivo. Our study suggests
that GLP-1R agonists do not promote the growth of ovarian cancer and may even
have anticancer effect on selected diabetic patients with ovarian cancer.
PMID- 27496642
TI - Naringin protects against HIV-1 protease inhibitors-induced pancreatic beta-cell
dysfunction and apoptosis.
AB - INTRODUCTION: The protective effects of grapefruit-derived naringin against HIV-1
Protease Inhibitors (PIs)-associated oxidative damage to pancreatic beta-cells
and apoptosis were investigated in RIN-5F cells in culture. METHODS: Cells in
culture medium were challenged with 11-25 mM glucose with or without nelfinavir
(1-10 MUM), saquinavir (1-10 MUM) and atazanavir (5-20 MUM), respectively for 24
h to determine insulin secretion. The cells were further treated with nelfinavir
(10 MUM), saquinavir (10 MUM), atazanavir (20 MUM) with and without naringin or
glibenclamide (10 MUM) for 24 h to determine insulin secretion, lipid
peroxidation, Superoxide Dismutase (SOD) activity, glutathione (GSH) levels, ATP
production and caspase-3 and-9 activities, respectively. RESULTS: Glucose
dependent insulin secretion was significantly reduced by PIs in a concentration
dependent manner. Treatment with either naringin or glibenclamide significantly
reduced lipid peroxidation, Superoxide Dismutase (SOD) activities and also
increased glutathione (GSH) and ATP levels in the cells that were treated with
PIs. Furthermore, naringin or glibenclamide significantly reduced caspase-3 and
caspase-9 activities in cells that were treated with PIs. CONCLUSIONS: PIs impair
beta-cell functions by increasing oxidative stress and apoptosis. Treatment with
naringin protected RIN-5F cells from PI-induced oxidative damage and apoptosis.
Our results therefore suggest that nutritional supplements with naringin could
prevent pancreatic beta-cell dysfunction and the attendant metabolic
complications caused by PIs in patients on antiretroviral therapy.
PMID- 27496643
TI - Crosstalk between C/EBP homologous protein (CHOP) and glucocorticoid receptor in
lung cancer.
AB - Loss of homeostasis triggers the endoplasmic reticulum (ER) stress response and
activates the unfolded protein response (UPR) resulting in the induction of the
CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). Glucocorticoids
(GCs), via the glucocorticoid receptor (GR), regulate numerous physiological
processes in an effort to maintain homeostasis. Previous studies demonstrated
that glucocorticoids suppress ER stress by enhancing correct folding of secreted
proteins and degradation of misfolded proteins. Here, we describe a novel
crosstalk between ER-stress and the glucocorticoid receptor signaling. We showed
that treatment of wild type mice with Tunicamycin (inducer of ER-stress)
increased GR protein levels in the lungs. Treatment of A549 cells (human lung
cancer cells) with ER stress inducers modulated the Dexamethasone-induced
subcellular localization of GR and the phosphorylated forms of GR (pGRSer211 and
pGRSer203) with concomitant changes in the expression of primary GR-target genes.
We demonstrated a significant protein-protein interaction between GR and CHOP,
(GR-CHOP heterocomplex formation) under ER stress conditions. The functional
consequences of ER stress- GR signaling crosstalk were assessed and demonstrated
that long time exposure (24-48 h) of A549 cells to dexamethasone (10(-6) M)
reversed the Tunicamycin-induced cell death, a phenomenon associated with
parallel increases in GR protein content, increases in cell survival parameters
and decreases in cell apoptosis-related parameters. Our study provides evidence
that there is a cross talk between ER-stress and GR signaling, this being
associated with mutual functional antagonism between CHOP and GR-mediated
pathways in lung cells with important implications in lung cell function.
PMID- 27496645
TI - Aged rats show dominant modulation of lower frequency hippocampal theta rhythm
during running.
AB - Aging causes considerable decline in both physiological and mental functions,
particularly cognitive function. The hippocampal theta rhythm (4-12Hz) is related
to both cognition and locomotion. Aging-related findings of the frequency and
amplitude of hippocampal theta oscillations are inconsistent and occasionally
contradictory. This inconsistency may be due to the effects of the sleep/wake
state and different frequency subbands being overlooked. We assumed that aged
rats have lower responses of the hippocampal theta rhythm during running, which
is mainly due to the dominant modulation of theta frequency subbands related to
cognition. By simultaneously recording electroencephalography, physical activity
(PA), and the heart rate (HR), this experiment explored the theta oscillations
before, during, and after treadmill running at a constant speed in 8-week-old
(adult) and 60-week-old (middle-aged) rats. Compared with adult rats, the middle
aged rats exhibited lower theta activity in all frequency ranges before running.
Running increased the theta frequency (Frq, 4-12Hz), total activity of the whole
theta band (total power, TP), activity of the middle theta frequency (MT, 6.5
9.5Hz), and PA in both age groups. However, the middle-aged rats still showed
fewer changes in these parameters during the whole running process. After the
waking baseline values were substracted, middle-aged rats showed significantly
fewer differences in DeltaFrq, DeltaTP, and DeltaMT but significantly more
differences in low-frequency theta activity (4.0-6.5Hz) and HR than the adult
rats did. Therefore, the decreasing activity and response of the whole theta band
in the middle-aged rats resulted in dominant modulation of the middle to lower
frequency (4.0-9.5Hz) theta rhythm. The different alterations in the theta rhythm
during treadmill running in the two groups may reflect that learning decline with
age.
PMID- 27496644
TI - Paranasal sinus osteomas: Diagnosis and treatment.
AB - INTRODUCTION: Osteoma is the most common benign tumor of the nose and paranasal
sinuses. It is a slow-growing bony tumor, often asymptomatic, occurring mainly in
frontal and ethmoid sinuses. Theories regarding the origin of osteomas are still
discussed. The aims of the study were to describe diagnosis circumstances in our
series and to set out our respective indications for open and endoscopic
approaches in the treatment of nasosinusal osteomas. PATIENTS AND METHODS: A
retrospective study was conducted on the files of all the patients treated for a
paranasal sinus osteoma in our department between 1990 and 2013. Diagnosis
circumstances and kind of treatment were collected and analyzed. RESULTS: The
files of 45 patients (mean age: 49.2; sex-ratio: 1.19) could be collected. The
most common symptom was headache found in all patients. The most common location
was the frontal sinus (30 cases). Thirty-nine open procedures were performed.
Four osteomas were removed under endoscopic assistance. In one case, a combined
approach has been used. Overall complication rate was 11.1%. Symptoms improved in
all patients. Two recurrences were observed. DISCUSSION: Surgical indications in
paranasal sinus osteomas are theorically well codified. However, approaches
remain controversial. In our experience, the preferred approach was the open one.
Endoscopic techniques, when indicated, are more challenging and need
sophisticated instrumentation and a long learning curve.
PMID- 27496646
TI - Now We Know: Assessing Sexual Assault Criminal Justice Case Processing in an
Urban Community Using the Sexual Assault Nurse Practitioner Evaluation Toolkit.
AB - Campbell and colleagues developed an evaluation Toolkit for use by sexual assault
nurse examiners (SANEs) to assess criminal case outcomes in adult sexual assault
cases seen by SANE programs (Campbell, Townsend, Shaw, Karim, & Markowitz, 2014;
Campbell, Bybee, et al., 2014). The Toolkit provides step-by-step directions and
an easy-to-use statistical program. This study describes implementation of the
Toolkit in Salt Lake County, the first site outside the pilot sites to utilize
the program. The Toolkit revealed that, in Salt Lake County from 2003 to 2011,
only 6% of adult sexual assault cases were successfully prosecuted. These
findings prompted multiple community discussions, media attention, and a call to
action to improve the investigation and prosecution of adult sexual assault
cases. The primary purpose of this case report is to encourage other SANE teams
and communities to use the Toolkit by sharing the successful experience of Salt
Lake County in implementing the Toolkit.Video Abstract available for additional
insights from Dr. Valentine (see Supplemental Digital Content 1,
http://links.lww.com/JFN/A19).
PMID- 27496647
TI - Humor: Power Conveying Social Structures Inside Forensic Mental Health Nursing.
AB - According to research literature, humor inside the staff-patient interaction
seems to be significant in the area of forensic mental healthcare. However,
existing literature on the subject is limited. Therefore, the aim of this study
was to explore the characteristics of the use humor by forensic mental health
staff members in interactions with forensic mental health inpatients. The study
included 32 forensic mental health staff members, used 307 hours of participant
observations, 48 informal interviews, and seven formal semistructured interviews.
Outcomes identify four themes concerning the conveyance of power to, from, and
between forensic mental health staff and patients as they interact: (a) "the
informal use: the human-to-human approach," characterized by an informal use of
humor and without any reference to mental health issues; (b) the "formal use of
humor: the staff-patient approach," characterized as formal with a view on the
patient as mentally ill, unable to understand humor, and with the aim of using
humor to prevent conflicts or negative behavior; (c) "protest against requested
care: the human-patient approach," characterized by the use of humor as a protest
against requested care; and the use of (d) "inadequacy humor: the staff-human
approach," characterized by the use of inadequacy-humor referring to, for
example, patients' physical features. Recommendations and clinical implications
are discussed.
PMID- 27496648
TI - Illustrations of Unexpected Infant Sleep Deaths.
AB - Case illustrations from central Indiana provide the narrative for infant
suffocations because of unsafe sleep environments. Accidental strangulation or
suffocation in bed is caused by co-bedding, blankets and pillows in cribs, or
wedging and entrapment. Knowledge of the evidence-based risks associated with
case data may assist further in the prevention of unexpected infant sleep deaths
and may better inform best practice for death scene investigation including
forensic nurses.
PMID- 27496649
TI - The Histologic Classifications of Lung Adenocarcinomas Are Discriminable by
Unique Lineage Backgrounds.
AB - OBJECTIVES: Lung adenocarcinomas are a heterogeneous set of diseases with
distinct genetic and histologic characteristics. Besides the discovery of
oncogenic mutations and introduction of the histologic classifications (2011
International Association for the Study of Lung Cancer/American Thoracic
Society/European Respiratory Society and 2015 WHO), increasing evidence has
linked this intertumor heterogeneity to the lung lineage-specific pathways and
lineage genes. Therefore, in this study, we assessed the gene expression of
identified lung lineage genes to study their role in distinguishing lung
adenocarcinoma diversities. METHODS: A total of 278 surgically resected lung
adenocarcinomas were included. Each case was evaluated for genetic mutations and
histologic classification. Lineage genes associated with respiratory tract
differentiation (NK2 homeobox 1 gene [NKX2-1], GATA protein binding 6 gene
[GATA6], foxhead box J1 gene [FOXJ1], and SAM pointed domain containing ETS
transcription factor gene [SPDEF]) and stem/basal-like status (inhibitor of DNA
binding 2, HLH protein gene [ID2], POU class 5 homeobox 1 gene [POU5F1], SRY-box
2 gene [SOX2], and v-myc avian myelocytomatosis viral oncogene homolog gene
[MYC]) were selected. mRNA expression of these genes in each tumor sample was
assessed by quantitative real-time polymerase chain reaction and normalized to
paired normal lung tissue. RESULTS: Distinct lineage gene expressions were found
on the basis of genetic and histologic diversities. Expression of NKX2-1, GATA6,
FOXJ1, and POU5F1 exhibited a significant linear relationship across histologic
subgroups that was independent of genetic mutation status. Expression levels of
NKX2-1 and POU5F1 were also associated with EGFR mutation status, independent of
histologic subtypes. Further analysis revealed that the overexpression of SPDEF
defined longer relapse-free survivals, especially in stage I disease.
CONCLUSIONS: For the first time, we showed the unique lineage backgrounds of
different histologic subtypes and oncogenic mutations. Assessing this added
parameter might be beneficial in discriminating intertumor heterogeneity,
advancing target exploration, developing theranostic/prognostic biomarkers, and
designing clinical trials.
PMID- 27496651
TI - Anatomical Segmentectomy and Wedge Resections Are Associated with Comparable
Outcomes for Patients with Small cT1N0 Non-Small Cell Lung Cancer.
AB - OBJECTIVES: Sublobar resection is advocated for patients with NSCLC and
compromised cardiopulmonary reserve, and for selected patients with early stage
disease. Anatomic segmentectomy (AS) has traditionally been considered superior
to wedge resection (WR), but well-balanced comparative studies are lacking. We
hypothesize that WR and AS are associated with comparable oncologic outcomes for
patients with cT1N0 NSCLC. METHODS: A retrospective review of a prospective
database was performed (2000-2014) for cT1N0 patients, excluding patients with
multiple primary tumors, carcinoid tumors, adenocarcinoma in situ, and minimally
invasive adenocarcinoma. Demographic, clinical, and pathological data were
reviewed. Overall survival (OS) and disease-free survival (DFS) were estimated
using the Kaplan-Meier method and differences compared using log-rank test.
Multivariable analysis (MVA) of factors affecting DFS was performed by Cox
regression analysis. For further comparison of the effect of resection type on
survival, propensity score matching (i.e., by age, sex, Charlson comorbidity
index, percent forced expiratory volume in 1 second (FEV1%), clinical tumor size,
and tumor maximum standardized uptake value) was performed to obtain balanced
cohorts of patients undergoing WR and AS (n = 76 per group). RESULTS: Two hundred
eighty-nine patients met our selection criteria, including WR in 160 and AS in
129. Poor performance status and limited cardiopulmonary reserve were the primary
indications for sublobar resection in 76% of WR patients and in 62% of AS
patients (p = 0.011). Thirteen patients (4.5%) had pN1/2 disease. Patients
undergoing AS were more likely to have nodal sampling/dissection [123 (95%)
versus 112 (70%); p < 0.001], more stations sampled (3 versus 2; p < 0.001), and
more total nodes resected (7 versus 4; p = 0.001). However, there was no
difference between patients undergoing WR versus AS in local recurrence [15
versus 14; p = 0.68] or 5-year DFS (51% versus 53%; p = 0.7; median follow-up 34
months). Univariate analysis showed no effect of extent of resection on DFS
[hazard ratio 1.07 (95% confidence interval 0.74-1.56); p = 0.696]. MVA showed
that only tumor maximum standardized uptake value was associated with worse DFS
[hazard ratio 1.07 (95% confidence interval 1.01-1.13); p = 0.016]. In the
propensity-matched analysis of balanced subgroups, there was also no difference
(p = 0.950) in 3- or 5-year DFS in cT1N0 patients undergoing WR (65% and 49%) or
AS (68% and 49%). CONCLUSIONS: Our data show that WR and AS are comparable
oncologic procedures for carefully staged cT1N0 NSCLC patients. Although AS is
associated with a more thorough lymph node dissection, this did not translate to
a survival benefit in this patient population with a low rate of nodal
metastases.
PMID- 27496650
TI - Relationship between Overall Survival and Response or Progression-Free Survival
in Advanced Non-Small Cell Lung Cancer Patients Treated with Anti-PD-1/PD-L1
Antibodies.
AB - INTRODUCTION: Alternative predictive end points for overall survival (OS), such
as tumor response and progression-free survival (PFS), are useful in the early
detection of drug efficacy; however, they have not been fully investigated in
patients with advanced NSCLC treated with anti-programmed death protein 1 (PD
1)/programmed death ligand 1 (PD-L1) antibodies. METHODS: In a systematic review
of the reported prospective clinical trials, data for response rate, median PFS,
and median OS were extracted from 12 arms in 10 reported clinical trials using
anti-PD-1/PD-L1 antibody, and their correlation was investigated. In a
retrospective analysis at our institution, OS was compared according to tumor
response on 5- to 9-week computed tomography scans and status of being
progression-free at 8, 16, and 24 weeks by landmark analysis in 71 patients with
advanced NSCLC treated with anti-PD-1/PD-L1 antibodies between 2013 and 2015.
RESULTS: In a systematic review, moderate correlations between median OS and
median PFS (p = 0.120, r = 0.473) and between median OS and response rate (p =
0.141, r = 0.452) were identified using the Spearman correlation coefficient,
although these correlations were not statistically significant. In a
retrospective analysis of patients treated at our institution, disease control
(partial response [PR]/stable disease versus progressive disease/not evaluable),
and progression-free status at 8, 16, and 24 weeks significantly predicted OS
(Cox proportional hazards model, PR/stable disease versus progressive disease/not
evaluable, p = 0.0104, HR = 3.041; 8-week progression-free yes versus no, p =
0.0183, HR = 2.684; 16-week progression-free yes versus no, p = 0.0036, HR =
4.009; and 24-week progression-free yes versus no, p = 0.0002, HR = 12.726).
CONCLUSIONS: Both disease control (PR plus stable disease status) and landmark
progression-free survival were correlated with OS, with the longer interval
landmark PFS being the best predictor of survival in patients with NSCLC treated
with anti-PD-1/PD-L1 antibodies.
PMID- 27496653
TI - Comment on "Further improvement on delay-range-dependent robust absolute
stability for Lur'e uncertain systems with interval time-varying delays" by P.
Liu [ISA Trans. 58(2015)58-66].
AB - In a recent paper (ISA Transactions (2015)58: 58-66), an integral inequality has
been proposed to reduce the conservativeness of stability conditions for Lur'e
uncertain systems. We point out that there exist some errors in Theorems 1-8, and
the correct theorems are presented. Finally, the allowable maximum admissible
upper bound (MAUB) listed in Tables 1-5 have been recalculated by using the
correct results.
PMID- 27496652
TI - LincRNA-p21 Impacts Prognosis in Resected Non-Small Cell Lung Cancer Patients
through Angiogenesis Regulation.
AB - INTRODUCTION: Long intergenic noncoding RNA-p21 (lincRNA-p21) is a long noncoding
RNA transcriptionally activated by tumor protein p53 (TP53) and hypoxia inducible
factor 1 alpha subunit (HIF1A). It is involved in the regulation of TP53
dependent apoptosis and the Warburg effect. We have investigated the role of
lincRNA-p21 in NSCLC. METHODS: LincRNA-p21 expression was assessed in tumor and
normal tissue from 128 patients with NSCLC and correlated with time to relapse
and cancer-specific survival (CSS). H23, H1299, and HCC-44 cell lines were
cultured in hypoxic conditions after silencing of lincRNA-p21. The TaqMan human
angiogenesis array was used to explore angiogenesis-related gene expression.
Levels of the protein vascular endothelial growth factor A were measured by
enzyme-linked immunosorbent assay in the cell supernatants. Angiogenic capability
was measured by human umbilical vein endothelial cell tube formation assay.
Microvascular density in tumor samples was analyzed by immunohistochemistry.
RESULTS: LincRNA-p21 was down-regulated in tumor tissue, but no association was
observed with TP53 mutational status. High lincRNA-p21 levels were associated
with poor CSS in all patients (p = 0.032). When patients were classified
according to histological subtypes, the impact of lincRNA-p21 was confined to
patients with adenocarcinoma in both time to relapse (p = 0.006) and CSS (p <
0.001). To explain the poor outcome of patients with high lincRNA-p21 expression,
we studied the role of lincRNA-p21 in angiogenesis in vitro and observed a global
downregulation in the expression of angiogenesis-related genes when lincRNA-p21
was inhibited. Moreover, supernatants from lincRNA-p21-inhibited cells were
significantly less angiogenic and had lower levels of secreted vascular
endothelial growth factor A than controls did. Finally, tumor samples with high
lincRNA-p21 levels had higher microvascular density. CONCLUSIONS: Our findings
suggest that lincRNA-p21 affects outcome in patients with NSCLC adenocarcinoma
through the regulation of angiogenesis.
PMID- 27496654
TI - Activation of delta-opioid receptor contributes to the antinociceptive effect of
oxycodone in mice.
AB - Oxycodone has been used clinically for over 90 years. While it is known that it
exhibits low affinity for the multiple opioid receptors, whether its
pharmacological activities are due to oxycodone activation of the opioid receptor
type or due to its active metabolite (oxymorphone) that exhibits high affinity
for the mu-opioid receptors remains unresolved. Ross and Smith (1997) reported
the antinociceptive effects of oxycodone (171nmol, i.c.v.) are induced by
putative kappa-opioid receptors in SD rat while others have reported oxycodone
activities are due to activation of mu- and/or delta-opioid receptors. In this
study, using male mu-opioid receptor knock-out (MOR-KO) mice, we examined whether
delta-opioid receptor was involved in oxycodone antinociception. Systemic
subcutaneous (s.c.) administration of oxycodone (above 40mg/kg) could induce a
small but significant antinociceptive effect in MOR-KO mice by the tail flick
test. Delta-opioid receptor antagonist (naltrindole, 10mg/kg or 20mg/kg, i.p.)
could block this effect. When oxycodone was injected directly into the brain of
MOR-KO mice by intracerebroventricular (i.c.v.) route, oxycodone at doses of
50nmol or higher could induce similar level of antinociceptive responses to those
observed in wild type mice at the same doses by i.c.v. Delta-opioid receptor
antagonists (naltrindole at 10nmol or ICI 154,129 at 20MUg) completely blocked
the supraspinal antinociceptive effect of oxycodone in MOR-KO mice. Such
oxycodone antinociceptive responses were probably not due to its active
metabolites oxymorphone because (a) the relative low level of oxymorphone was
found in the brain after systemically or centrally oxycodone injection using
LC/MS/MS analysis; (b) oxymorphone at a dose that mimics the level detected in
the mice brain did not show any significant antinocieption effect; (c) oxycodone
exhibits equal potency as oxymorphone albeit being a partial agonist in
regulating [Ca(2+)]I transients in a clonal cell line expressing high level of mu
opioid receptor. These data suggest that oxycodone by itself can activate both
the mu- and delta-opioid receptors and that delta-opioid receptors may contribute
to the central antinociceptive effect of oxycodone in mice.
PMID- 27496655
TI - "To Reverse or Not To Reverse?": The Answer Is Clear!
PMID- 27496656
TI - Nondepolarizing Neuromuscular Blocking Agents, Reversal, and Risk of
Postoperative Pneumonia.
AB - BACKGROUND: Residual postoperative paralysis from nondepolarizing neuromuscular
blocking agents (NMBAs) is a known problem. This paralysis has been associated
with impaired respiratory function, but the clinical significance remains
unclear. The aims of this analysis were two-fold: (1) to investigate if
intermediate-acting NMBA use during surgery is associated with postoperative
pneumonia and (2) to investigate if nonreversal of NMBAs is associated with
postoperative pneumonia. METHODS: Surgical cases (n = 13,100) from the Vanderbilt
University Medical Center National Surgical Quality Improvement Program database
who received general anesthesia were included. The authors compared 1,455
surgical cases who received an intermediate-acting nondepolarizing NMBA to 1,455
propensity score-matched cases who did not and 1,320 surgical cases who received
an NMBA and reversal with neostigmine to 1,320 propensity score-matched cases who
did not receive reversal. Postoperative pneumonia incidence rate ratios (IRRs)
and bootstrapped 95% CIs were calculated. RESULTS: Patients receiving an NMBA had
a higher absolute incidence rate of postoperative pneumonia (9.00 vs. 5.22 per
10,000 person-days at risk), and the IRR was statistically significant (1.79; 95%
bootstrapped CI, 1.08 to 3.07). Among surgical cases who received an NMBA, cases
who were not reversed were 2.26 times as likely to develop pneumonia after
surgery compared to cases who received reversal with neostigmine (IRR, 2.26; 95%
bootstrapped CI, 1.65 to 3.03). CONCLUSIONS: Intraoperative use of intermediate
nondepolarizing NMBAs is associated with developing pneumonia after surgery.
Among patients who receive these agents, nonreversal is associated with an
increased risk of postoperative pneumonia.
PMID- 27496657
TI - Resting-state Network-specific Breakdown of Functional Connectivity during
Ketamine Alteration of Consciousness in Volunteers.
AB - BACKGROUND: Consciousness-altering anesthetic agents disturb connectivity between
brain regions composing the resting-state consciousness networks (RSNs). The
default mode network (DMn), executive control network, salience network (SALn),
auditory network, sensorimotor network (SMn), and visual network sustain
mentation. Ketamine modifies consciousness differently from other agents,
producing psychedelic dreaming and no apparent interaction with the environment.
The authors used functional magnetic resonance imaging to explore ketamine
induced changes in RSNs connectivity. METHODS: Fourteen healthy volunteers
received stepwise intravenous infusions of ketamine up to loss of responsiveness.
Because of agitation, data from six subjects were excluded from analysis. RSNs
connectivity was compared between absence of ketamine (wake state [W1]), light
ketamine sedation, and ketamine-induced unresponsiveness (deep sedation [S2]).
RESULTS: Increasing the depth of ketamine sedation from W1 to S2 altered DMn and
SALn connectivity and suppressed the anticorrelated activity between DMn and
other brain regions. During S2, DMn connectivity, particularly between the medial
prefrontal cortex and the remaining network (effect size beta [95% CI]: W1 = 0.20
[0.18 to 0.22]; S2 = 0.07 [0.04 to 0.09]), and DMn anticorrelated activity (e.g.,
right sensory cortex: W1 = -0.07 [-0.09 to -0.04]; S2 = 0.04 [0.01 to 0.06]) were
broken down. SALn connectivity was nonuniformly suppressed (e.g., left parietal
operculum: W1 = 0.08 [0.06 to 0.09]; S2 = 0.05 [0.02 to 0.07]). Executive control
networks, auditory network, SMn, and visual network were minimally affected.
CONCLUSIONS: Ketamine induces specific changes in connectivity within and between
RSNs. Breakdown of frontoparietal DMn connectivity and DMn anticorrelation and
sensory and SMn connectivity preservation are common to ketamine and propofol
induced alterations of consciousness.
PMID- 27496659
TI - Corrigendum to 'Physical properties and depth of cure of a new short fiber
reinforced composite' [Dent Mater 29 (8) (2013) 835-841].
PMID- 27496658
TI - Intergenerational associations in numerical approximation and mathematical
abilities.
AB - Although growing evidence suggests a link between children's math skills and
their ability to estimate numerical quantities using the approximate number
system (ANS), little is known about the sources underlying individual differences
in ANS acuity and their relation with specific mathematical skills. To examine
the role of intergenerational transmission of these abilities from parents to
children, the current study assessed the ANS acuities and math abilities of 54
children (5-8 years old) and their parents, as well as parents' expectations
about children's math skills. Children's ANS acuity positively correlated with
their parents' ANS acuity, and children's math abilities were predicted by unique
combinations of parents' ANS acuity and math ability depending on the specific
math skill in question. These findings provide the first evidence of
intergenerational transmission of an unlearned, non-verbal numerical competence
and are an important step toward understanding the multifaceted parental
influences on children's math abilities.
PMID- 27496660
TI - Periprosthetic fracture in the elderly with anatomic modular cementless
hemiarthroplasty.
AB - BACKGROUND: The use of an anatomic cementless stem in hemiarthroplasties for
femoral intracapsular proximal fracture has been debated, notably because of bone
weakness and/or morphological defects related to osteoporosis. We therefore
conducted a retrospective study in subjects over 75 years of age who had received
an anatomic stem partially coated with hydroxyapatite. The objectives were to
determine: 1) the incidence of periprosthetic fractures (PPFs) and, 2) the
influence of anatomic factors, including the Cortical Bone Ratio (CBR) (the
relation between the endosteal and external diameter of the femoral diaphysis
10cm below the lesser trochanter). HYPOTHESIS: The risk of PPF with an anatomic
cementless implant is greater than with cemented stems. MATERIAL AND METHODS: We
retrospectively analyzed 233 patients followed up for 5 years after their
surgery. The stem used was an anatomic stem with a modular neck partially coated
with hydroxyapatite. The risk factors examined were age, gender, history of
osteoporotic fractures, diverse causes of secondary osteoporosis, and proximal
bone stock according to various referenced radiological indices such as the CBR.
RESULTS: Twenty patients (15%) were lost to follow-up, 74 had died (32%) but did
not undergo revision for PPF, 15 of the 139 survivors at the last follow-up
(10.8%) had had a PPF, five (3.6%; four females, one male) were early fractures
(<=2 months after implantation), ten (7.2%; two females, eight males) were late
fractures (>2 months). Male gender was protective for PPF occurrence (RR=0.129;
95%CI (0.04-0.39); P=0.0003), whereas secondary factors of osteoporosis
(RR=2.035; 95%CI (1.11-3.72); P=0.0211), and CBR>0.49 (RR=227.42; 95%CI (1.072
48,226.76); P=0.0471) were found as risk factors of PPF. DISCUSSION: The PPF rate
was greater than that related to cemented stems, requiring that morphological and
clinical factors of bone weakness (collected with the patient history and related
to osteoporosis) be taken into account. A CBR>0.49 requires caution on the use of
this type of stem. LEVEL OF EVIDENCE: Level 4. Retrospective study.
PMID- 27496661
TI - Predictors of 30-day mortality following hip/pelvis fractures.
AB - INTRODUCTION: With the cost of healthcare in the United States reaching $2.9
trillion in 2013 and expected to increase with a growing geriatric population,
the Center for Medicare and Medicaid Services (CMS) and Hospital Quality Alliance
(HQA) began publicly reporting 30-day mortality rates so that hospitals and
physicians may begin to confront clinical problems and promote high-quality and
patient-centered care. Though the 30-day mortality is considered a highly
effective tool in measuring hospital performance, little data actually exists
that explores the rate and risk factors for trauma-related hip and pelvis
fractures. Therefore, in this study, we sought to explore the risk factors
associated with 30-day mortality in trauma-related hip and pelvic fractures.
MATERIALS AND METHODS: Utilizing the American College of Surgeons National
Surgical Quality Improvement Program (ACS-NSQIP) database, 341,062 patients
undergoing orthopaedic procedures from 2005 to 2013 were identified through a
Current Procedural Terminology (CPT) code search. A second CPT code search
identified 24,805 patients who sustained a hip/pelvis fracture. Patient
demographics, preoperative comorbidities, operative characteristics and
postoperative complications were collected and compared using Chi-squared test,
Wilcoxon-Mann-Whitney test and multivariate logistic regression analysis.
RESULTS: Preoperative and postoperative risk factors for 30-day mortality
following a hip/pelvis fracture were found: ASA classification, ascites,
disseminated cancer, dyspnea, functional status, history of congestive heart
failure (CHF), history of chronic obstructive pulmonary disease (COPD), a recent
blood transfusion, and the postoperative complications: pneumonia, myocardial
infarction, stroke, and septic shock. DISCUSSION: Several preoperative patient
risk factors and postoperative complications greatly increased the odds for
patient mortality following 30-days after initial surgery. Orthopaedic surgeons
can utilize these predictive risk factors to better improve patient care. LEVEL
OF EVIDENCE: Retrospective study. Level IV.
PMID- 27496662
TI - A comparison of double Endobutton and triple Endobutton techniques for acute
acromioclavicular joint dislocation.
AB - PURPOSE OF THE STUDY: The purpose of this study was to evaluate the results of
patients treated with either double Endobutton device or triple Endobutton device
for acute acromioclavicular joint dislocations. PATIENTS AND METHODS: Eighty
patients were randomized to operative stabilization either by double Endobutton
device (group A, 40) or by triple Endobutton device (group B, 40). Preoperative
variables included the patients' age, sex, the affected side, cause of injury,
Rockwood classification and time from injury to surgery. Peri-operative variables
were incision length, blood loss, the operative time and the radiation time,
length of hospitalization and hospital costs. Postoperative variables were
complications, the Constant and VAS scores and the ability to return to previous
work. The coracoclavicular (CC) distance of the affected shoulder was assessed on
a standard radiograph and compared with the contralateral normal one. RESULTS:
The average follow-up time of group A was 26.5+/-7.3months and group B was 24.2+/
6.6months. The overall complication rate was similar in both groups (26/40 vs.
24/40, P=0.644). There were no significant differences in the mean incision
length, blood loss, the operative and radiation time, length of hospitalization,
the Constant and VAS scores, and the ability to return to previous work between
the two groups. However, the patients of group B had more hospital costs
(3802.5+/-258.5 vs. 2433.6+/-182.5 USD, P=0.000). The radiological assessment
revealed no significant difference in the CC distance between the two groups
(P=0.625). DISCUSSIONS: Triple Endobutton technique did not show significant
clinical advantages over double Endobutton technique. LEVEL OF EVIDENCE: Level II
prospective randomized study.
PMID- 27496663
TI - Fifty years of research and development of cosmeceuticals: a contemporary review.
AB - Facial rejuvenation can be categorized into skincare and facial contouring.
Research and development of cosmeceuticals is aimed at addressing the major signs
of photoaging: wrinkles, dyschromia, and sallowness. Assessment of photoaging
comes in clinical and photographic forms; a photonumeric scale developed by
Griffiths et al. has been assured of its validity and reliability for the
assessment of severity of photoaging in qualitative studies. Treatment of
photoaging comes in two categories: preventive and reversal of signs; whilst
sunfactors are the most efficient and essential in preventing photodamage,
research and development of cosmeceuticals for facial rejuvenation has been
robust, thanks to several landmark studies in the last fifty years, funded by
some of the forerunners in contemporary cosmetic industry. Stem cell research
remains the current forerunner in research concerning cosmeceuticals.
Nevertheless, high-quality, randomized control trials remain scarce within the
contemporary literature, and more research and trials without funding by the
industry are required to give rise to impartial comparisons between various
cosmeceutical products. The "perfect cream" for facial rejuvenation remains
elusive.
PMID- 27496665
TI - Comparison of Motor-Evoked Potentials Versus Somatosensory-Evoked Potentials as
Early Indicators of Neural Compromise in Rat Model of Spinal Cord Compression.
AB - STUDY DESIGN: Randomized controlled study comparing the efficacy of
intraoperative somatosensory-evoked potentials (SSEPs) versus transcranial motor
evoked potentials (TcMEPs) as early indicators of neural compromise and
predictors of postoperative function in a rat model of spinal cord compression.
OBJECTIVE: To compare the relative efficacy of SSEPs and TcMEPs to detect spinal
cord compromise and predict postoperative functional deficit after spinal cord
compression. SUMMARY OF BACKGROUND DATA: There is controversy regarding the
efficacy of SSEPs versus TcMEPs to detect intraoperative spinal cord compromise
and predict functional outcomes. Previous trials provide some guidance as to the
role of each modality in spinal cord monitoring but randomized controlled trials,
which are not feasible in humans, are lacking. METHODS: Twenty-four adult male
Wistar rats were evenly divided into three experimental groups and one control
group. The experimental groups were determined according to the length of time
that 100% TcMEP signal loss was maintained: 0, 5, or 15 minutes. All animals had
standardized preoperative functional testing. Spinal cord compromise was
initiated utilizing a validated protocol, which involved compression via a
balloon catheter introduced into the thoracic sublaminar space. Both SSEPs and
TcMEPs were recorded during cord compression for each experimental group.
Functional behavioral testing using two validated methods (tilt and modified
Tarlov) was repeated 24 hours after termination of spinal cord compression. Post
hoc, animals were redistributed into two functional subgroups, noncompromised and
compromised, for statistical analysis. RESULTS: TcMEPs consistently detected
spinal cord compromise either in advance of or at the same time as SSEPs;
however, the delay in SSEP response was not significant for cases when
compromised postoperative function resulted. Both SSEP and TcMEP amplitude
recovery correlated well with postoperative functional scores. CONCLUSION: TcMEPs
are more sensitive to spinal cord compromise than SSEPs, but the recovery
profiles of both SSEP and TcMEP amplitudes are good predictors of postoperative
function. LEVEL OF EVIDENCE: 2.
PMID- 27496664
TI - Life Expectancy After Cervical En Bloc Laminoplasty: Analysis of Data Following
More Than 20 Years.
AB - STUDY DESIGN: Case series. OBJECTIVE: To clarify the following questions How long
after cervical laminoplasty did the patients die? What were the causes of the
death? Was the severity of the neurological dysfunction related to early death?
SUMMARY OF BACKGROUND DATA: Life expectancy in patients with cervical myelopathy
is unclear. Cervical laminoplasty was performed in 216 patients between 1981 and
1994. It was possible to follow 148 patients for more than 20 years. We used the
data of the 68 survivors and the 80 patients had already died. METHODS: As for
the patients who died by the final follow-up, the survival rate was analyzed by a
Kaplan-Meier plot; the results were compared between the patients with cervical
spondylosis (CS) and the patients with ossification of the posterior longitudinal
ligament (OPLL). The causes of the death were assessed. The neurological
evaluation was graded using the score devised by the Japanese Orthopaedic
Association (JOA). The pre- and postoperative scores were compared between the
patients in the died group (D group) and the surviving patients group (S group).
RESULTS: The mean period from surgery to death was 13.4 +/- 7.4 years. There was
no difference in the survival rate between patients with CS and patients with
OPLL. The most frequent cause of death was malignant tumor followed by ischemic
heart disease. Preoperative JOA score in the D group was lower than that in the S
group. There was no statistical difference in postoperative JOA score between the
two groups. CONCLUSION: The patients who underwent cervical laminoplasty caused
by compression myelopathy due to CS and OPLL had a long life expectancy,
averaging more than 13 years. Life expectancy did not differ between patients
with CS and patients with OPLL. Neurological deficit did not directly affect the
life expectancy. LEVEL OF EVIDENCE: 4.
PMID- 27496666
TI - Adults With Idiopathic Scoliosis Diagnosed at Youth Experience Similar Physical
Activity and Fracture Rate as Controls.
AB - STUDY DESIGN: Cross-sectional. OBJECTIVE: To describe physical activity level and
fracture rates in adults with idiopathic scoliosis, diagnosed before maturity,
and to compare with a control group. SUMMARY OF BACKGROUND DATA: A previous study
found a lower level of sporting activities in adults treated for idiopathic
scoliosis compared with controls. Other studies have shown a lower bone mass in
adults with idiopathic scoliosis compared with controls. METHODS: One thousand
two hundred seventy-eight adults (aged 18-71 yr) with idiopathic scoliosis and
214 controls (aged 18-70 yr) were included and answered the International
Physical Activity Questionnaire - Short Form (IPAQ-SF) and questions about
previous fractures. The three scoliosis treatment groups (untreated n = 360,
brace n = 460, and surgically treated n = 458) were compared. Furthermore, a
comparison based on onset (juvenile n = 169 or adolescent n = 976) was performed.
Achieved weekly moderate activity level and metabolic equivalent task (MET)
minutes/week were assessed for patients and controls. Statistical comparisons
were made with analysis of covariance with adjustments for age, body mass index,
and sex. RESULTS: The proportion achieving weekly moderate activity level was 962
out of 1278 for individuals with idiopathic scoliosis (75%) and 157 out of 214
(73%) for controls (P = 0.40). The scoliosis patients reported 2016 MET
minutes/week (median value) and the controls 2456 (P = 0.06). Fracture rates did
not differ (P = 0.72). Fewer surgically treated individuals achieved moderate
activity level (P = 0.046) compared with the untreated and the previously braced
individuals. No difference was seen regarding MET-minutes/week (P = 0.86). No
differences were seen between individuals with a juvenile onset compared with
individuals with an adolescent onset (all P >= 0.05). CONCLUSION: Adults with
idiopathic scoliosis have similar physical activity level and do not sustain more
fractures compared with controls. Adults with surgically treated idiopathic
scoliosis have slightly lower physical activity level than previously braced and
untreated patients. Onset of idiopathic scoliosis does not affect physical
activity level. LEVEL OF EVIDENCE: 2.
PMID- 27496667
TI - Hospital-Acquired Conditions in Adult Spinal Deformity Surgery: Predictors for
Hospital-Acquired Conditions and Other 30-Day Postoperative Outcomes.
AB - STUDY DESIGN: A retrospective study of prospectively collected data. OBJECTIVE:
The aim of this study was to identify risk factors in developing hospital
acquired conditions (HACs) and association of HACs with other 30-day
complications in the adult spinal deformity (ASD) population. SUMMARY OF
BACKGROUND DATA: HACs are subject to a nonpayment policy by the Center for
Medicare and Medicaid Services and provide an incentive for medical institutions
to improve patient safety. HACs in the ASD population may further exacerbate the
already high rates of postoperative morbidity and mortality. METHODS: The 2010 to
2014 ACS-NSQIP database was queried using Current Procedural Terminology (CPT)
codes for adults who had fusion for spinal deformity. Patients were divided into
two cohorts on the basis of the development of an HAC, as defined as a case of
surgical site infection, urinary tract infection, or venous thromboembolism.
Univariate and multivariate logistic regression analyses were employed to
determine predictors for HACs and association of HACs with other 30-day
postoperative outcomes. RESULTS: Five thousand eight hundred nineteen patients
met the inclusion criteria for the study of whom 313 (5.4%) had an HAC.
Multivariate logistic regression analysis revealed that age 61 to 70 versus <=50
years [odds ratio (OR) = 1.58, 1.10-2.27, P = 0.013], 71 to 80 versus <=50 years
(OR = 1.94, 1.31-2.87, P = 0.001), and >80 versus <=50 years (OR = 2.30, 1.21
4.37, P = 0.011), dependent/partially dependent versus independent functional
status (OR = 1.74, 1.13-2.68, P = 0.011), combined versus anterior surgical
approach (OR = 2.46, 1.43-4.24, P = 0.001), and posterior versus anterior
surgical approach (OR = 1.64, 1.19-2.25, P = 0.002), osteotomies (OR = 1.61, 1.22
2.13, P = 0.001), steroid use (OR = 2.19, 1.39-3.45, P = 0.001), obesity (OR =
1.38, 1.09-1.74, P = 0.007), and operation time >=4 hours (OR = 2.42, 1.82-3.21,
P < 0.001) were predictive factors in developing an HAC. CONCLUSION: Several
modifiable and nonmodifiable factors (age, functional status, surgical approach,
utilization of osteotomies, steroid use, obesity, and operation time >=4 hours)
were associated with developing an HAC. HACs were also risk factors for other
postoperative complications. LEVEL OF EVIDENCE: 3.
PMID- 27496668
TI - Transpars Microscopic Approach for the Treatment of Purely Foraminal Herniated
Lumbar Disc: A Clinical, Radiological, Two-center Study.
AB - STUDY DESIGN: This is a prospective two-center study. OBJECTIVE: The aim of this
study was to assess the safety and efficacy of treating patients with lumbar
foraminal disc herniations via a microscopic transpars approach, with a clinical
and radiological follow-up evaluation. SUMMARY OF BACKGROUND DATA: Purely
foraminal lumbar disc herniations comprise about 5% of all lumbar herniated
intervertebral discs. Operative management can be technically difficult, and the
optimum surgical treatment remains controversial. METHODS: From January 2012 to
January 2015, 47 patients were prospectively recruited. Patients were followed-up
as outpatients at 1 week after discharge, then at 1, 6, and 12 months.A clinical
multiparametric evaluation of patients including numeric rating scale (NRS),
drugs intake, Macnab criteria, and working days lost was used.Postoperative
dynamic x-rays (flexion, extension) were performed in all cases 12 months after
surgery. RESULTS: No surgery-related complications occurred.Among the 35 patients
who were not retired at the time of the study, 29 patients returned to work and
to normal daily activities within 60 days after surgery.Pain evaluation at
discharge showed a significant improvement of NRS score, from 8.93 to 1.45 at 12
months. Root palsy significantly improved in all cases already at 1-month follow
up. Drugs intake analysis showed that at 6-month follow-up, no patients used
steroids, or opioids, 17 patients used non-steroidal anti-inflammatory drugs when
needed, and 29 patients (61.7%) used no drugs for pain relief. No significant
variations occurred at 12-month-follow-up.At 12-month follow-up, excellent or
good outcome (following Macnab criteria) was achieved in 36 (76.6%) and 8 (17%)
patients, respectively.There were no cases of spinal instability at 12-month
radiological evaluation.No recurrence occurred at follow-up. CONCLUSION:
Transpars microscopic approach is effective and safe for the treatment of FLDH,
but larger studies are needed. LEVEL OF EVIDENCE: 3.
PMID- 27496669
TI - Risks of inhibitors from recombinant factor VIII: a quarter of a century to reach
the conclusion.
PMID- 27496670
TI - Identification of a novel homozygous mutation Arg459Pro in SYNJ1 gene of an
Indian family with autosomal recessive juvenile Parkinsonism.
AB - BACKGROUND: A novel homozygous missense mutation (c.773G > A, p.Arg258Gln) in
Synaptojanin 1 (SYNJ1, 21q22.2) has recently been reported in two Italian and one
Iranian consanguineous families with autosomal recessive juvenile Parkinsonism
(ARJP). Contribution of this synaptic gene related to Parkinsonism phenotypes in
other populations still remains unidentified. METHODS: An ARJP family with two
affected siblings characterized by frequent tremor with bradykinesia and rigidity
was recruited in this study. Both siblings showed intense dyskinesia and dystonia
on administration of Syndopa. The family was analyzed for both mutations and exon
dosage variations in PARKIN, PINK1 and DJ1. Further, whole exome sequencing was
performed in two affected and one unaffected sibling in the family. RESULTS: We
identified a novel homozygous mutation (c.1376C > G, p.Arg459Pro) in SYNJ1
segregating in this family. This p.Arg459Pro mutation was not observed in 285
additional Parkinson disease (PD) samples (32 familial, 81 early onset and 172
late onset) screened by PCR-Sanger-sequencing. It was also absent in dbSNP, 1000
Genomes, ExAC, NHLBI-ESP database and in >250 ethnically matched exomes available
in our laboratory. The arginine residue is highly conserved across species and
predicted to be damaging by several in silico tools. As with the previous
mutation p.Arg258Gln, p.Arg459Pro is also present in Sac 1 domain of SYNJ1
wherein p.Arg258Gln mutation has already been described to impair the phosphatase
activity. CONCLUSIONS: We report another novel mutation in SYNJ1 of an Indian
consanguineous ARJP family. Finding an additional mutation in this gene further
supports the involvement of SYNJ1 in PD pathogenesis across different
ethnicities.
PMID- 27496671
TI - Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex
correlation or causality in stimulation-mediated effects?
AB - Transcranial current stimulation approaches include neurophysiologically distinct
non-invasive brain stimulation techniques widely applied in basic, translational
and clinical research: transcranial direct current stimulation (tDCS),
oscillating transcranial direct current stimulation (otDCS), transcranial
alternating current stimulation (tACS) and transcranial random noise stimulation
(tRNS). Prefrontal tDCS seems to be an especially promising tool for clinical
practice. In order to effectively modulate relevant neural circuits, systematic
research on prefrontal tDCS is needed that uses neuroimaging and neurophysiology
measures to specifically target and adjust this method to physiological
requirements. This review therefore analyses the various neuroimaging methods
used in combination with prefrontal tDCS in healthy and psychiatric populations.
First, we provide a systematic overview on applications, computational models and
studies combining neuroimaging or neurophysiological measures with tDCS. Second,
we categorise these studies in terms of their experimental designs and show that
many studies do not vary the experimental conditions to the extent required to
demonstrate specific relations between tDCS and its behavioural or
neurophysiological effects. Finally, to support best-practice tDCS research we
provide a methodological framework for orientation among experimental designs.
PMID- 27496673
TI - Reply.
PMID- 27496675
TI - A case of deep dissecting hematoma: different managements resulting in similar
outcomes.
PMID- 27496674
TI - Reply.
PMID- 27496676
TI - Effect of the In Vitro Boundary Conditions on the Surface Strain Experienced by
the Vertebral Body in the Elastic Regime.
AB - The vertebral strength and strain can be assessed in vitro by both using isolated
vertebrae and sets of three adjacent vertebrae (the central one is loaded through
the disks). Our goal was to elucidate if testing single-vertebra-specimens in the
elastic regime provides different surface strains to three-vertebrae-segments.
Twelve three-vertebrae sets were extracted from thoracolumbar human spines. To
measure the principal strains, the central vertebra of each segment was prepared
with eight strain-gauges. The sets were tested mechanically, allowing comparison
of the surface strains between the two boundary conditions: first when the same
vertebra was loaded through the disks (three-vertebrae-segment) and then with the
endplates embedded in cement (single-vertebra). They were all subjected to four
nondestructive tests (compression, traction, torsion clockwise, and
counterclockwise). The magnitude of principal strains differed significantly
between the two boundary conditions. For axial loading, the largest principal
strains (along vertebral axis) were significantly higher when the same vertebra
was tested isolated compared to the three-vertebrae-segment. Conversely,
circumferential strains decreased significantly in the single vertebrae compared
to the three-vertebrae-segment, with some variations exceeding 100% of the strain
magnitude, including changes from tension to compression. For torsion, the
differences between boundary conditions were smaller. This study shows that, in
the elastic regime, when the vertebra is loaded through a cement pot, the surface
strains differ from when it is loaded through the disks. Therefore, when single
vertebrae are tested, surface strain should be taken with caution.
PMID- 27496677
TI - Anti-Inflammatory and Anti-Oxidant Effects of p-Chloro-phenyl-selenoesterol on
TNBS-Induced Inflammatory Bowel Disease in Mice.
AB - This study aims to investigate the protective effect of p-chloro-phenyl
selenoesterol [PCS; 0,2 mg/kg; 10 ml/kg i.g.) in colitis induced by 2,4,6
trinitrobenzene sulfonic acid [TNBS; 2 mg/100 ul 50% ethanol; intrarectally) in
mice. Several parameters including weight, length, histological analyses
determination, thiobarbituric acid reactive species, reactive species levels,
superoxide dismutase, catalase, and myeloperoxidase (MPO) activity of colon were
evaluated. The serum levels of tumor necrosis factor alpha [TNF-alpha) and
interleukin 6 [IL-6) were also assessed. Treatment with PCS reduced the clinical
and histopathologic severity of TNBS-induced colitis, characterized by colon
length reduction and increased colon weight and microscopic intestinal
inflammation. The therapeutic effects of PCS in this model were associated with
significant decrease in proinflammatory cytokines TNF-alpha and IL-6 and decrease
in MPO activity. Furthermore, combined with improvements in inflammatory
parameters, treatment with the PCS was able to decrease oxidative stress and to
prevent the decrease in antioxidant defenses in animals with TNBS-induced
colitis. This finding suggests that PCS can improve experimental colitis in mice
and it could be a potential therapeutic agent for the treatment of patients with
IBD. J. Cell. Biochem. 118: 709-717, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27496672
TI - Behavioral, emotional and neurobiological determinants of coronary heart disease
risk in women.
AB - Women have more of the stress-related behavioral profile that has been linked to
cardiovascular disease than men. For example, women double the rates of stress
related mental disorders such as depression and posttraumatic stress disorder
(PTSD) than men, and have higher rates of exposure to adversity early in life.
This profile may increase women's long-term risk of cardiometabolic conditions
linked to stress, especially coronary heart disease (CHD). In addition to having
a higher prevalence of psychosocial stressors, women may be more vulnerable to
the adverse effects of these stressors on CHD, perhaps through altered
neurobiological physiology. Emerging data suggest that young women are
disproportionally susceptible to the adverse effects of stress on the risk of
cardiovascular disease, both in terms of initiating the disease as well as
worsening the prognosis in women who have already exhibited symptoms of the
disease. Women's potential vulnerability to psychosocial stress could also help
explain their higher propensity toward abnormal coronary vasomotion and
microvascular disease compared with men.
PMID- 27496678
TI - Pharmacokinetics of Cefepime in Patients with Cancer and Febrile Neutropenia in
the Setting of Hematologic Malignancies or Hematopoeitic Cell Transplantation.
AB - STUDY OBJECTIVE: To evaluate the steady-state pharmacokinetic parameters of
standard cefepime dosing regimens in a hematologic malignancy and hematopoietic
cell transplant patient population with febrile neutropenia. DESIGN: Open-label,
single-center, prospective pharmacokinetic study. SETTING: National Cancer
Institute-designated cancer center. PATIENTS: Nine adults with hematologic
malignancies or hematopoietic cell transplants who had febrile neutropenia and
were admitted to a hematology-oncology service between January and July 2014.
INTERVENTION: Patients received empirical cefepime 2 g every 8 hours,
administered as a 30-minute intravenous infusion, for febrile neutropenia.
MEASUREMENTS AND MAIN RESULTS: Steady-state cefepime serum concentrations were
measured after at least 2 days of continuous therapy. Venous blood samples were
intensively sampled between 0 and 8 hours after the start of the 30-minute
infusion at steady state. Seven of the nine patients had a hematologic malignancy
diagnosis of acute leukemia, lymphoma, or myeloma, and two patients had a germ
cell tumor diagnosis. Noncompartmental analysis revealed mean +/- SD parameters
as follows at steady state: area under the plasma concentration-time curve from 0
8 hours 222.9 +/- 72.9 mg hour/L, maximum concentration 120.9 +/- 21.8 mg/L,
clearance 9.7 +/- 3.7 L/hour, apparent volume of distribution 19.2 +/- 4.65 L,
and elimination half-life 1.4 +/- 0.3 hours. A one-compartment pharmacokinetic
model identified a mean +/- SD volume of distribution of 20.9 +/- 1.3 L and an
elimination rate constant of 0.39 +/- 0.03 hour(-1) . The mean estimated
percentage of time that drug concentration remains above the pathogen minimum
inhibitory concentration (fT>MIC) in serum was 55%, 77%, and 99% at MICs of 16,
8, and 4 mg/L, respectively. CONCLUSION: Patients with hematologic malignancies
or hematopoietic cell transplants who had febrile neutropenia demonstrated
homogeneous calculated cefepime volumes and clearances. The population parameters
presented in this study may aid in the calculation of patient-specific fT>MIC for
similar patients.
PMID- 27496679
TI - Thalidomide and POEMS syndrome: a cautious step forward.
PMID- 27496681
TI - Shoulder Arthroscopy in Adults 60 or Older: Risk Factors That Correlate With
Postoperative Complications in the First 30 Days.
AB - PURPOSE: To investigate the 30-day postoperative adverse event (AE) rates of
adults 60 years or older after shoulder arthroscopy and identify risk factors for
complications in this patient population. METHODS: Patients aged 60 or more who
underwent shoulder arthroscopy were identified in the American College of
Surgeons National Surgery Quality Improvement Program database from 2006 to 2013
using 12 Current Procedural Terminology codes related to shoulder arthroscopy.
Complications were categorized as severe AEs, minor AEs, and infectious AEs for
separate analyses. Pearson's chi2 tests were used to identify associations
between patient characteristics and AE occurrence and binary logistic regression
for multivariate analysis of independent risk factors. RESULTS: In total, 7,867
patients were included for analysis. Overall, 1.6% (n = 127) of the older adults
experienced at least one AE with 1.1% (n = 90) severe AEs, 0.6% (n = 46) minor
AEs, and 0.4% (n = 28) infectious complications. Multivariate analysis revealed
that age 80 years or older (odds ratio [OR] = 2.2, 95% confidence interval [CI] =
1.2-2.7, P = .01), body mass index greater than 35 (OR = 1.8, 95% CI = 1.1-2.7, P
= .01), functionally dependent status (OR = 2.9, 95% CI = 1.3-6.8, P = .01),
American Society of Anesthesiologists class greater than 2 (OR = 1.5, 95% CI =
1.0-2.2, P = .04), congestive heart failure (OR = 6.1, 95% CI = 1.8-21.2, P =
.03), disseminated cancer (OR = 7.9, 95% CI = 1.4-43.9, P = .02), and existence
of an open wound at the time of surgery (OR = 4.0, 95% CI = 1.1-14.6, P = .03)
were independently associated with the occurrence of an AE. Nineteen of the
patients included in the study required readmission to the hospital within the 30
day period for an overall readmission rate of 0.2%. CONCLUSIONS: Patients 60
years or older who underwent shoulder arthroscopy for a variety of indications
have a low overall 30-day postoperative complication rate of 1.6%. Although low,
this is a higher rate than previously reported for the overall shoulder
arthroscopy population. Independent patient characteristics associated with
increased risk of AE occurrence included age 80 years or older, body mass index
greater than 35, functional dependent status, American Society of
Anesthesiologists score of 3 or 4, congestive heart failure, disseminated cancer,
and existence of an open wound. LEVEL OF EVIDENCE: Level III, retrospective
comparative study.
PMID- 27496680
TI - Safety and efficacy of thalidomide in patients with POEMS syndrome: a
multicentre, randomised, double-blind, placebo-controlled trial.
AB - BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin
changes (POEMS) syndrome is a rare cause of demyelinating neuropathy, with multi
organ involvement characterised by plasma cell dyscrasia and VEGF overproduction.
No treatments have been established for patients with POEMS syndrome who are not
eligible for stem-cell transplantation. Thalidomide suppresses VEGF and plasma
cell proliferation. We aimed to assess the safety and efficacy of thalidomide for
the treatment of POEMS syndrome. METHODS: We did a randomised, double-blind,
placebo-controlled, phase 2/3 trial at 12 hospitals in Japan. Adults (age >=20
years) with POEMS syndrome who were ineligible for autotransplantation were
randomly assigned (1:1) by a minimisation method to treatment with oral
dexamethasone (12 mg/m(2) per day on the first 4 days of every 28-day cycle) plus
either oral thalidomide (200 mg daily) or placebo for six cycles. All study
personnel and patients were masked to treatment allocation. The primary endpoint
was the reduction rate of serum VEGF concentrations at 24 weeks. Analysis was by
intention to treat. This study is registered with the UMIN Clinical Trials
Registry, UMIN000004179. FINDINGS: Between Nov 11, 2010, and July 3, 2014, we
randomly assigned 25 patients to receive either thalidomide (n=13) or placebo
(n=12); one patient in the placebo group was excluded from analyses because of a
protocol violation. The adjusted mean VEGF concentration reduction rate at 24
weeks was 0.39 (SD 0.34) in the thalidomide group compared with -0.02 (0.54) in
the placebo group (adjusted mean difference 0.41, 95% CI 0.02-0.80; p=0.04). Mild
sinus bradycardia was more frequent in the thalidomide group than in the placebo
group (seven [54%] vs zero; p=0.006). Five patients had serious adverse events:
three in the thalidomide group (transient cardiac arrest, heart failure, and
dehydration) and two in the placebo group (ileus and fever). No deaths occurred
during the randomised study. In the 48-week open-label study period (n=22), newly
developed adverse events were sinus bradycardia (n=4), constipation (n=5), and
mild sensory neuropathy (n=5). Two patients died in the open-label study; both
patients were initially in the placebo group, and the cause of death was
progression of the disease. INTERPRETATION: Thalidomide reduces serum VEGF
concentrations and represents a new treatment for patients with POEMS syndrome
who are not eligible for stem-cell transplantation. Thalidomide treatment poses a
risk of bradycardia; however, the benefits are likely to exceed the risk.
FUNDING: Japanese Ministry of Health, Labour, and Welfare, and Fujimoto
Pharmaceuticals.
PMID- 27496682
TI - The composition of surface wax on trichomes of Arabidopsis thaliana differs from
wax on other epidermal cells.
AB - To protect plants against biotic and abiotic stress, the waxy cuticle must coat
all epidermis cells. Here, two independent approaches addressed whether cell-type
specific differences exist between wax compositions on trichomes and other
epidermal cells of Arabidopsis thaliana, possibly with different protection
roles. First, the total waxes from a mutant lacking trichomes (gl1) were compared
to waxes from wild type and a trichome-rich mutant (cpc tcl1 etc1 etc3). In the
stem wax, compounds with aliphatic chains longer than 31 carbons (derived from
C32 precursors) increased in relative abundance in cpc tcl1 etc1 etc3 over gl1.
Similarly, the leaf wax from the trichome-rich mutant contained higher amounts of
C32+ compounds as compared to gl1. Second, leaf trichomes were isolated, and
their waxes were analyzed. The wax mixtures of the trichome-rich mutant and the
wild type were similar, comprising alkanes and alkenes as well as branched and
unbranched primary alcohols. The direct analyses of trichome waxes confirmed that
they contained relatively high concentrations of C32+ compounds, compared with
the pavement cell wax inferred from analysis of gl1 leaves. Finally, the cell
type-specific wax compositions were put into perspective with expression patterns
of wax biosynthesis genes in trichomes and pavement cells. Analyses of published
transcriptome data (Marks et al., ) revealed that core enzymes involved in
elongation of wax precursors to various carbon chain lengths are expressed
differentially between epidermis cell types. By combining the chemical and gene
expression data, we identified promising gene candidates involved in the
formation of C32+ aliphatic chains.
PMID- 27496683
TI - Antifouling booster biocides in coastal waters of Panama: First appraisal in one
of the busiest shipping zones.
AB - A baseline study for antifouling booster biocides in coastal waters of Panama is
presented. Solid Phase Extraction (SPE) was used for extraction and Liquid
Chromatography tandem Mass Spectrometry (LC-MS/MS) was applied for the
quantification of irgarol 1051, diuron, (2-thiocyanomethylthio)benzothiazole
(TCMTB), 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) and dichlofluanid.
TCMTB, DCOIT and dichlofluanid were not detected in any seawater sample, while
irgarol 1051 and diuron were found in four out of thirteen areas (<0.3 to 5.0ngL
1 and <2.7 to 70ngL-1, respectively). Although the hotspots were identified in
areas influenced by marinas and in one of the ports, diuron and irgarol 1051
levels were all lower than the threshold levels set by the Environmental Quality
Standard of United Kingdom. However, this is only a snapshot of the status of
costal water contamination by antifouling booster biocides and a more
comprehensive assessment is needed to assess risks associated to long term
exposure.
PMID- 27496684
TI - Influence of geographic setting on thermal discharge from coastal power plants.
AB - Characteristics of thermal discharge from three coastal power plants were studied
in China. The three plants, Zhuhai Power Plant, Chaozhou Power Plant and Huilai
Power Plant, are located in estuary, bay and open sea, respectively. The water
temperatures and ocean currents surrounding the outlet of the three power plants
were monitored. The results show that the temperature rise became smaller as the
spread of thermal discharge moved toward the open sea, which confirms the results
of previous studies. The results also indicated that the influence range of
thermal discharge from a coastal power plant is determined by geographic setting.
The temperature rise range of the Chaozhou Plant, which is located in a bay, was
the largest, followed by that of the Zhuhai Plant located in an estuary, and the
temperature rise range of the Huilai Plant located in an open sea was the
smallest.
PMID- 27496685
TI - Spatial and temporal analysis of the risks posed by polychlorinated biphenyl and
metal contaminants in dab (Limanda limanda) collected from waters around England
and Wales.
AB - The metals cadmium, mercury and lead, and the ICES7 CB levels were analysed in
the common dab Limanda limanda to investigate whether concentrations of these
determinants are at levels above established OSPAR assessment criteria around
England and Wales. The results indicate that CB118 is above the OSPAR derived EAC
at 22 out of 29 sampled stations, with 15 showing significant reductions. Cadmium
is increasing significantly at six stations with two sites in the North Sea
breaching corresponding OSPAR EAC. Mean results for all other PCBs and metals
stayed below the EAC thresholds, with Hg concentrations even falling below BAC
levels at South Eddystone located in the western English Channel. This study
shows that PCBs banned over 20years ago are still found at concentrations in fish
liver tissues which may pose a health risk to both the individual fish and their
predators.
PMID- 27496686
TI - The Physician Payments Sunshine Act: a smokescreen if no action!
PMID- 27496688
TI - Reply.
PMID- 27496687
TI - The Management of Myelomeningocele Study: obstetrical outcomes and risk factors
for obstetrical complications following prenatal surgery.
AB - BACKGROUND: The Management of Myelomeningocele Study was a multicenter randomized
trial to compare prenatal and standard postnatal closure of myelomeningocele. The
trial was stopped early at recommendation of the data and safety monitoring
committee and outcome data for 158 of the 183 randomized women published.
OBJECTIVE: In this report, pregnancy outcomes for the complete trial cohort are
presented. We also sought to analyze risk factors for adverse pregnancy outcome
among those women who underwent prenatal myelomeningocele repair. STUDY DESIGN:
Pregnancy outcomes were compared between the 2 surgery groups. For women who
underwent prenatal surgery, antecedent demographic, surgical, and pregnancy
complication risk factors were evaluated for the following outcomes: premature
spontaneous membrane rupture <=34 weeks 0 days (preterm premature rupture of
membranes), spontaneous membrane rupture at any gestational age, preterm delivery
at <=34 weeks 0 days, nonintact hysterotomy (minimal uterine wall tissue between
fetal membranes and uterine serosa, or partial or complete dehiscence at
delivery), and chorioamniotic membrane separation. Risk factors were evaluated
using chi2 and Wilcoxon tests and multivariable logistic regression. RESULTS: A
total of 183 women were randomized: 91 to prenatal and 92 to postnatal surgery
groups. Analysis of the complete cohort confirmed initial findings: that prenatal
surgery was associated with an increased risk for membrane separation,
oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor, and
earlier gestational age at birth. In multivariable logistic regression of the
prenatal surgery group adjusting for clinical center, earlier gestational age at
surgery and chorioamniotic membrane separation were associated with increased
risk of spontaneous membrane rupture (odds ratio, 1.49; 95% confidence interval,
1.01-2.22; and odds ratio, 2.96, 95% confidence interval, 1.05-8.35,
respectively). Oligohydramnios was associated with an increased risk of
subsequent preterm delivery (odds ratio, 9.21; 95% confidence interval, 2.19
38.78). Nulliparity was a risk factor for nonintact hysterotomy (odds ratio,
3.68; 95% confidence interval, 1.35-10.05). CONCLUSION: Despite the confirmed
benefits of prenatal surgery, considerable maternal and fetal risk exists
compared with postnatal repair. Early gestational age at surgery and development
of chorioamniotic membrane separation are risk factors for ruptured membranes.
Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk
factor for nonintact hysterotomy at delivery.
PMID- 27496689
TI - Quality of life outcomes associated with treatment of human immunodeficiency
virus (HIV) facial lipoatrophy.
AB - Facial lipoatrophy (FLA), characterized by a decrease in facial volume, has a
high prevalence in patients with human immunodeficiency virus (HIV) infection
treated with long-term highly active antiretroviral therapy (HAART). The social
stigmatization that results from such changes in facial appearance has led some
HIV patients to discontinue HAART. The use of fillers is one method of restoring
facial volume. A critical outcome of treatment concerns the patient's quality of
life (QoL). Although many studies have assessed patient satisfaction, as well as
the social and psychological outcomes associated with the correction of HIV FLA,
fewer studies have assessed QoL. We reviewed treatment options for HIV FLA with a
specific focus on QoL outcomes. Our analysis revealed that the following
treatments were associated with improvements in QoL: poly-l-lactic acid; calcium
hydroxylapatite; hyaluronic acid; polyacrylamide gel; polyalkylamide gel;
polymethylmethacrylate; silicone oil; and autologous fat transfer. The treatment
of HIV FLA with these agents appears to improve QoL as assessed by various QoL
instruments. Additional studies are required to identify a unifying QoL
instrument to effectively assess longitudinal QoL outcomes and to compare
treatment modalities.
PMID- 27496690
TI - BPTU, an allosteric antagonist of P2Y1 receptor, blocks nerve mediated inhibitory
neuromuscular responses in the gastrointestinal tract of rodents.
AB - P2Y1 receptors mediate nerve mediated purinergic inhibitory junction potentials
(IJP) and relaxations in the gastrointestinal (GI) tract in a wide range of
species including rodents and humans. A new P2Y1 antagonist, with a non
nucleotide structure, BPTU, has recently been described using X-ray
crystallography as the first allosteric G-protein-coupled receptor antagonist
located entirely outside of the helical bundle. In this study, we tested its
effect on purinergic responses in the gastrointestinal tract of rodents using
electrophysiological and myographic techniques. BPTU concentration dependently
inhibited purinergic inhibitory junction potentials and inhibition of spontaneous
motility induced by electrical field stimulation in the colon of rats (EC50 = 0.3
MUM) and mice (EC50 = 0.06 MUM). Mechanical inhibitory responses were also
concentration-dependently blocked in the stomach of both species. Compared to
MRS2500, BPTU displays a lower potency. In the rat colon nicotine induced
relaxation was also blocked by BPTU. BPTU also blocked the cessation of
spontaneous contractility elicited by ADPbetaS and the P2Y1 agonist MRS2365. We
conclude that BPTU is a novel antagonist with different structural and functional
properties than nucleotidic antagonists that is able to block the P2Y1 receptor
located at the neuromuscular junction of the GI tract.
PMID- 27496691
TI - GLP-1 and estrogen conjugate acts in the supramammillary nucleus to reduce food
reward and body weight.
AB - The obesity epidemic continues unabated and currently available pharmacological
treatments are not sufficiently effective. Combining gut/brain peptide, GLP-1,
with estrogen into a conjugate may represent a novel, safe and potent, strategy
to treat diabesity. Here we demonstrate that the central administration of GLP-1
estrogen conjugate reduced food reward, food intake, and body weight in rats. In
order to determine the brain location of the interaction of GLP-1 with estrogen,
we avail of single-photon emission computed tomography imaging of regional
cerebral blood flow and pinpoint a brain site unexplored for its role in feeding
and reward, the supramammillary nucleus (SUM) as a potential target of the
conjugated GLP-1-estrogen. We confirm that conjugated GLP-1 and estrogen directly
target the SUM with site-specific microinjections. Additional microinjections of
GLP-1-estrogen into classic energy balance controlling nuclei, the lateral
hypothalamus (LH) and the nucleus of the solitary tract (NTS) revealed that the
metabolic benefits resulting from GLP-1-estrogen injections are mediated through
the LH and to some extent by the NTS. In contrast, no additional benefit of the
conjugate was noted on food reward when the compound was microinjected into the
LH or the NTS, identifying the SUM as the only neural substrate identified here
to underlie the reward reducing benefits of GLP-1 and estrogen conjugate.
Collectively we discover a surprising neural substrate underlying food intake and
reward effects of GLP-1 and estrogen and uncover a new brain area capable of
regulating energy balance and reward.
PMID- 27496693
TI - Thirtieth Anniversary Issue of Clinical Rehabilitation: an introductory
editorial.
PMID- 27496692
TI - Oestrus synchronisation and superovulation alter the production and biochemical
constituents of ovine cervicovaginal mucus.
AB - Controlled breeding programmes utilising exogenous hormones are common in the
Australian sheep industry, however the effects of such programmes on
cervicovaginal mucus properties are lacking. As such, the aim of this study was
to investigate cervicovaginal (CV) mucus from naturally cycling (NAT),
progesterone synchronised (P4), prostaglandin synchronised (PGF2alpha), and
superovulated (SOV) Merino ewes. Experiment 1; volume, colour, spinnbarkeit,
chemical profile and protein concentration of mucus (NAT, P4, PGF2alpha and SOV;
n=5 ewes/treatment) during the follicular (5 d) and luteal phases (8 d) was
investigated. Experiment 2; in vivo mucus pH and in vitro mucus penetration by
frozen-thawed spermatozoa (NAT, P4 and SOV; n=11 ewes/treatment) was investigated
over oestrus (2 d) and the mid-luteal phase (pH only, 2 d). Oestrus mucus was
more abundant, clearer in colour and less proteinaceous than luteal phase mucus
(p<0.05). SOV increased mucus production and protein concentration (p<0.05) while
PGF2alpha reduced mucus volume (p<0.05). Mucus pH (oestrus 6.2-6.5), chemical
profile and mucus penetration by sperm were unchanged (p>0.05). Results indicate
that exogenous hormones used for controlled breeding affect cervicovaginal mucus
production, but few other tested characteristics. Further research is required to
explain fertility differences between synchronised and naturally cycling animals
following cervical AI.
PMID- 27496694
TI - Having an impact, making a difference: the Editor's review of the first 30 years.
AB - OBJECTIVES: To review publications in Clinical Rehabilitation over the last 30
years, discerning the original goals and whether they were met, and describing
major trends over the 30 years. METHODS: Personal review, backed up by data from
'most read' articles and 'most cited' articles, from yearly lists of all
controlled trials published in the journal and other sources. RESULTS: The
original goals included making rehabilitation better understood both within and
outside the speciality, and more scientific. The first goal is probably not
achieved, but the scientific standard of publication is much higher and it
routinely recommends the use of guidelines appropriate to the publication. The
journal has established a pre-eminent position in publishing randomized
controlled trials, systematic reviews and articles on goal-setting. It has
developed a series describing rehabilitation interventions. It aims to increase
consideration of the theoretical basis of rehabilitation practices. We would like
to think its impact has increased - but we cannot prove that! CONCLUSION: The
journal has established some credentials as being a source of clinically relevant
evidence and guidance across the whole field of rehabilitation and across most
disabling conditions.
PMID- 27496695
TI - How have research questions and methods used in clinical trials published in
Clinical Rehabilitation changed over the last 30 years?
AB - Research in rehabilitation has grown from a rare phenomenon to a mature science
and clinical trials are now common. The purpose of this study is to estimate the
extent to which questions posed and methods applied in clinical trials published
in Clinical Rehabilitation have evolved over three decades with respect to
accepted standards of scientific rigour. Studies were identified by journal,
database, and hand searching for the years 1986 to 2016.A total of 390 articles
whose titles suggested a clinical trial of an intervention, with or without
randomization to form groups, were reviewed. Questions often still focused on
methods to be used (57%) rather than what knowledge was to be gained. Less than
half (43%) of the studies delineated between primary and secondary outcomes;
multiple outcomes were common; and sample sizes were relatively small (mean 83,
range 5 to 3312). Blinding of assessors was common (72%); blinding of study
subjects was rare (19%). In less than one-third of studies was intention-to-treat
analysis done correctly; power was reported in 43%. There is evidence of
publication bias as 83% of studies reported either a between-group or a within
group effect. Over time, there was an increase in the use of parameter estimation
rather than hypothesis testing and there was evidence that methodological rigour
improved.Rehabilitation trialists are answering important questions about their
interventions. Outcomes need to be more patient-centred and a measurement
framework needs to be explicit. More advanced statistical methods are needed as
interventions are complex. Suggestions for moving forward over the next decades
are given.
PMID- 27496696
TI - Promoting physical activity in low back pain patients: six months follow-up of a
randomised controlled trial comparing a multicomponent intervention with a low
intensity intervention.
AB - OBJECTIVE: To assess a comprehensive multicomponent intervention against a low
intensity intervention for promoting physical activity in chronic low back pain
patients. DESIGN: Randomised controlled trial. SETTING: Inpatient rehabilitation
and aftercare. SUBJECTS: A total of 412 patients with chronic low back pain.
INTERVENTIONS: A multicomponent intervention (Movement Coaching) comprising of
small group intervention (twice during inpatient rehabilitation), tailored
telephone aftercare (twice after rehabilitation) and internet-based aftercare
(web 2.0 platform) versus a low level intensity intervention (two general
presentations on physical activity, download of the presentations). MAIN
MEASURES: Physical activity was measured using a questionnaire. Primary outcome
was total physical activity; secondary outcomes were setting specific physical
activity (transport, workplace, leisure time) and pain. Comparative group
differences were evaluated six months after inpatient rehabilitation. RESULTS: At
six months follow-up, 92 participants in Movement Coaching (46 %) and 100
participants in the control group (47 %) completed the postal follow-up
questionnaire. No significant differences between the two groups could be shown
in total physical activity (P = 0.30). In addition to this, workplace (P = 0.53),
transport (P = 0.68) and leisure time physical activity (P = 0.21) and pain (P =
0.43) did not differ significantly between the two groups. In both groups,
physical activity decreased during the six months follow-up. CONCLUSIONS: The
multicomponent intervention was no more effective than the low intensity
intervention in promoting physical activity at six months follow-up. The decrease
in physical activity in both groups is an unexpected outcome of the study and
indicates the need for further research.
PMID- 27496697
TI - The development and validation of a novel outcome measure to quantify mobility in
the dysvascular lower extremity amputee: the amputee single item mobility
measure.
AB - OBJECTIVE: This study describes the development and psychometric evaluation of a
novel patient-reported single-item mobility measure. DESIGN: Prospective cohort
study. SETTING: Four Veteran's Administration Medical Centers. SUBJECTS:
Individuals undergoing their first major unilateral lower extremity amputation;
198 met inclusion criteria; of these, 113 (57%) enrolled. INTERVENTIONS: None.
MAIN MEASURES: The Amputee Single Item Mobility Measure, a single item measure
with scores ranging from 0 to 6, was developed by an expert panel, and
concurrently administered with the Locomotor Capabilities Index-5 (LCI-5) and
other outcome measures at six weeks, four months, and 12 months post-amputation.
Criterion and construct validity, responsiveness, and floor/ceiling effects were
evaluated. Responsiveness was assessed using the standardized response mean.
RESULTS: The overall mean 12-month Amputee Single Item Mobility Measure score was
3.39 +/-1.4. Scores for transmetatarsal, transtibial, and transfemoral amputees
were 4.2 (+/-1.3), 3.2 (+/-1.5), and 2.9 (+/-1.1), respectively. Amputee Single
Item Mobility Measure scores demonstrated "large" and statistically significant
correlations with the LCI-5 scores at six weeks (r = 0.72), four months (r =
0.81), and 12 months (r = 0.86). At four months and 12 months, the correlation
between Amputee Single Item Mobility Measure scores and hours of prosthetic use
were r = 0.69 and r = 0.66, respectively, and between Amputee Single Item
Mobility Measure scores and Trinity Amputation and Prosthesis Experience Scales
functional restriction scores were r = 0.45 and r = 0.67, respectively. Amputee
Single Item Mobility Measure scores increased significantly from six weeks to 12
months post-amputation. Minimal floor/ceiling effects were demonstrated.
CONCLUSIONS: In the unilateral dysvascular amputee, the Amputee Single Item
Mobility Measure has strong criterion and construct validity, excellent
responsiveness, and does not exhibit floor/ceiling effects.
PMID- 27496698
TI - Determinants of pain and functioning in knee osteoarthritis: a one-year
prospective study.
AB - OBJECTIVE: To identify predictors of pain and disability in knee osteoarthritis.
DESIGN: A one-year prospective analysis of determinants of pain and functioning
in knee osteoarthritis. STUDY SETTING: Primary care providers in a medium-sized
city. PATIENTS: A total of 111 patients aged from 35 to 75 with clinical symptoms
and radiographic grading (Kellgren-Lawrence 2-4) of knee osteoarthritis who
participated in a randomized controlled trial. MAIN MEASURES: The outcome
measures were self-reported pain and function, which were recorded at 0, 3 and 12
months. Disease-specific pain and functioning were assessed using the pain and
function subscales of the Western Ontario and McMaster Universities (WOMAC)
Osteoarthritis Index. Generic physical and mental functioning were assessed using
the RAND-36 subscales for function, and physical and mental component summary
scores. Possible baseline predictors for these outcomes were 1) demographic,
socioeconomic and disease-related variables, and 2) psychological measures of
resources, distress, fear of movement and catastrophizing. RESULTS: Multivariate
linear mixed model analyses revealed that normal mood at baseline measured with
the Beck Anxiety Inventory predicted significantly better results in all measures
of pain (WOMAC P=0.02) and function (WOMAC P=0.002, RAND-36 P=0.002) during the
one-year follow-up. Psychological resource factors (pain self-efficacy P=0.012,
satisfaction with life P=0.002) predicted better function (RAND-36). Pain
catastrophizing predicted higher WOMAC pain levels (P=0.013), whereas fear of
movement (kinesiophobia) predicted poorer functioning (WOMAC P=0.046, RAND-36
P=0.024). CONCLUSIONS: Multiple psychological factors in people with knee
osteoarthritis pain are associated with the development of disability and longer
term worse pain.
PMID- 27496699
TI - A prospective observational study of outcomes from rehabilitation of elderly
patients with moderate to severe cognitive impairment.
AB - OBJECTIVES: To evaluate rehabilitation outcomes in patients with moderate to
severe cognitive impairment. DESIGN: Prospective observational cohort study.
SETTING: Rehabilitation unit for older people. SUBJECTS: A total of 116 patients
(70F) mean age (SD) 86.3 (6.4). Group 1: 89 patients with moderate cognitive
impairment (Mini-Mental State Examination 11-20); and Group 2: 27 patients with
severe cognitive impairment (Mini-Mental State Examination 0-10). INTERVENTION: A
personalised rehabilitation plan. MAIN MEASURES: Barthel Activity of Daily Living
score on admission and discharge, length of stay and discharge destination.
RESULTS: Of 116 patients, 64 (55.2%) showed an improvement in Barthel score. Mini
Mental State Examination was significantly higher in those who improved, 15.4 (SD
3.7) vs.13.2 (SD 5.1): p = 0.01. The mean Barthel score improved in both groups;
Group 1 - 14.7 (SD 19.1) vs. Group 2 - 9.3 (SD 16.3): p = 0.17. Of 84 home
admissions in Group 1, more patients returning home showed improvements of at
least 5 points in the Barthel score compared with nursing/residential home
discharges (32/37 - 86.5% vs. 10/28 - 35.7%: p = 0.0001). In Group 2 of 17 home
admissions, 6/6 (100%) home discharges showed improvement compared with 3/7
(42.8%) discharges to nursing/residential home (p = 0.07). In Group 1, a
discharge home was associated with significantly greater improvement in number of
Barthel items than a nursing/residential home discharge (3.27 (SD 2.07) vs. 1.86
(SD 2.32): p = 0.007). A similar non-significant pattern was noted for severe
cognitive impairment patients (3.5 (3.06) vs. 1.14 (1.06); p = 0.1). CONCLUSION:
Patients with moderate to severe cognitive impairment demonstrated significant
improvements in Barthel score and Barthel items showing that such patients can
and do improve with rehabilitation.
PMID- 27496700
TI - Short-term effects of goal-setting focusing on the life goal concept on
subjective well-being and treatment engagement in subacute inpatients: a quasi
randomized controlled trial.
AB - OBJECTIVE: To investigate the short-term effects of the life goal concept on
subjective well-being and treatment engagement, and to determine the sample size
required for a larger trial. DESIGN: A quasi-randomized controlled trial that was
not blinded. SETTING: A subacute rehabilitation ward. SUBJECTS: A total of 66
patients were randomized to a goal-setting intervention group with the life goal
concept (Life Goal), a standard rehabilitation group with no goal-setting
intervention (Control 1), or a goal-setting intervention group without the life
goal concept (Control 2). INTERVENTIONS: The goal-setting intervention in the
Life Goal and Control 2 was Goal Attainment Scaling. The Life Goal patients were
assessed in terms of their life goals, and the hierarchy of goals was explained.
The intervention duration was four weeks. MAIN MEASURES: Patients were assessed
pre- and post-intervention. The outcome measures were the Hospital Anxiety and
Depression Scale, 12-item General Health Questionnaire, Pittsburgh Rehabilitation
Participation Scale, and Functional Independence Measure. RESULTS: Of the 296
potential participants, 66 were enrolled; Life Goal (n = 22), Control 1 (n = 22)
and Control 2 (n = 22). Anxiety was significantly lower in the Life Goal (4.1 +/
3.0) than in Control 1 (6.7 +/-3.4), but treatment engagement was significantly
higher in the Life Goal (5.3 +/-0.4) compared with both the Control 1 (4.8 +/
0.6) and Control 2 (4.9 +/-0.5). CONCLUSIONS: The life goal concept had a short
term effect on treatment engagement. A sample of 31 patients per group would be
required for a fully powered clinical trial.
PMID- 27496701
TI - What are the barriers and facilitators to goal-setting during rehabilitation for
stroke and other acquired brain injuries? A systematic review and meta-synthesis.
AB - OBJECTIVE: To identify the barriers and facilitators to goal-setting during
rehabilitation for stroke and other acquired brain injuries. DATA SOURCES: AMED,
Proquest, CINAHL and MEDLINE. REVIEW METHODS: Two reviewers independently
screened, extracted data and assessed study quality using the Mixed Methods
Appraisal Tool and undertook thematic content analysis for papers examining the
barriers and facilitators to goal-setting during stroke/neurological
rehabilitation (any design). Last searches were completed in May 2016. RESULTS:
Nine qualitative papers were selected, involving 202 participants in total: 88
patients, 89 health care professionals and 25 relatives of participating
patients. Main barriers were: Differences in staff and patients perspectives of
goal-setting; patient-related barriers; staff-related barriers, and
organisational level barriers. Main facilitators were: individually tailored goal
setting processes, strategies to promote communication and understanding, and
strategies to avoid disappointment and unrealistic goals. In addition, patients'
and staff's knowledge, experience, skill, and engagement with goal-setting could
be either a barrier (if these aspects were absent) or a facilitator (if they were
present). CONCLUSION: The main barriers and facilitators to goal-setting during
stroke rehabilitation have been identified. They suggest that current methods of
goal-setting during inpatient/early stage stroke or neurological rehabilitation
are not fit for purpose.
PMID- 27496702
TI - Drug eluting antimicrobial vascular catheters: Progress and promise.
AB - Vascular catheters are critical tools in modern healthcare yet present
substantial risks of serious bloodstream infections that exact significant health
and economic burdens. Drug-eluting antimicrobial vascular catheters have become
important tools in preventing catheter-related bloodstream infections and their
importance is expected to increase as significant initiatives are expanded to
eliminate and make the occurrence of these infections unacceptable. Here we
review clinically significant and emerging drug-eluting antimicrobial catheters
within the categories of antibiotic, antiseptic, novel bioactive agents and
energy-enhanced drug eluting antimicrobial catheters. Important representatives
of each category are reviewed from the standpoints of mechanisms of action,
physical-chemical properties, safety, in vitro and clinical effectiveness.
PMID- 27496703
TI - Anti-thrombotic technologies for medical devices.
AB - Thrombosis associated with medical devices may lead to dramatic increases in
morbidity, mortality and increased health care costs. Innovative strategies are
being developed to reduce this complication and provide a safe biocompatible
interface between device and blood. This article aims to describe the biological
phenomena underlying device-associated thrombosis, and surveys the literature
describing current and developing technologies designed to overcome this
challenge. To reduce thrombosis, biomaterials with varying topographical
properties and incorporating anti-thrombogenic substances on their surface have
demonstrated potential. Overall, there is extensive literature describing
technical solutions to reduce thrombosis associated with medical devices, but
clinical results are required to demonstrate significant long-term benefits.
PMID- 27496705
TI - Oral absorption of peptides and nanoparticles across the human intestine:
Opportunities, limitations and studies in human tissues.
AB - In this contribution, we review the molecular and physiological barriers to oral
delivery of peptides and nanoparticles. We discuss the opportunities and
predictivity of various in vitro systems with special emphasis on human intestine
in Ussing chambers. First, the molecular constraints to peptide absorption are
discussed. Then the physiological barriers to peptide delivery are examined.
These include the gastric and intestinal environment, the mucus barrier, tight
junctions between epithelial cells, the enterocytes of the intestinal epithelium,
and the subepithelial tissue. Recent data from human proteome studies are used to
provide information about the protein expression profiles of the different
physiological barriers to peptide and nanoparticle absorption. Strategies that
have been employed to increase peptide absorption across each of the barriers are
discussed. Special consideration is given to attempts at utilizing endogenous
transcytotic pathways. To reliably translate in vitro data on peptide or
nanoparticle permeability to the in vivo situation in a human subject, the in
vitro experimental system needs to realistically capture the central aspects of
the mentioned barriers. Therefore, characteristics of common in vitro cell
culture systems are discussed and compared to those of human intestinal tissues.
Attempts to use the cell and tissue models for in vitro-in vivo extrapolation are
reviewed.
PMID- 27496706
TI - Device thrombosis and pre-clinical blood flow models for assessing
antithrombogenic efficacy of drug-device combinations.
AB - Thrombosis associated with blood-contacting devices is a complex process
involving several component interactions that have eluded precise definition.
Extensive investigations of individual biological modules such as protein
adsorption, coagulation cascade activation and platelet
activation/adhesion/aggregation have provided an initial foundation for
developing biomaterials for blood-contacting devices, but a material that is
intrinsically non-thrombogenic is yet to be developed. The well-recognized
association between fluid dynamics parameters such as shear stress, vortices,
stagnation and thrombotic processes such as platelet aggregation and coagulation
aggravate thrombosis on most device geometries that elicit these flow
disturbances. Thus, antithrombotic drugs that were developed to treat thrombosis
associated with vascular diseases such as atherosclerosis have also been adapted
to mitigate the risk of device thrombosis. However, balancing the risk of
bleeding with the antithrombotic efficacy of these drugs continues to be a
challenge, and surface modification of devices with these drug molecules to
mitigate device thrombosis locally has been explored. Pre-clinical blood flow
models to test the effectiveness of these drug-device combinations have also
evolved and several in-vitro, ex-vivo, and in-vivo test configurations are
available with their attendant merits and limitations. Despite considerable
efforts toward iterative design and testing of blood contacting devices and
antithrombogenic surface modifications, device thrombosis remains an unsolved
problem.
PMID- 27496708
TI - Androgen and Estrogen Receptors in Breast Cancer Coregulate Human UDP
Glucuronosyltransferases 2B15 and 2B17.
AB - Glucuronidation is an enzymatic process that terminally inactivates steroid
hormones, including estrogens and androgens, thereby influencing carcinogenesis
in hormone-dependent cancers. While estrogens drive breast carcinogenesis via the
estrogen receptor alpha (ERalpha), androgens play a critical role as prohormones
for estrogen biosynthesis and ligands for the androgen receptor (AR). In this
study, the expression and regulation of two androgen-inactivating enzymes, the
UDP-glucuronosyltransferases UGT2B15 and UGT2B17, was assessed in breast cancer.
In large clinical cohorts, high UGT2B15 and UGT2B17 levels positively influenced
disease-specific survival in distinct molecular subgroups. Expression of these
genes was highest in cases positive for ERalpha. In cell line models, ERalpha,
AR, and the transcription factor FOXA1 cooperated to increase transcription via
tandem binding events at their proximal promoters. ERalpha activity was dependent
on FOXA1, facilitated by AR activation, and potently stimulated by estradiol as
well as estrogenic metabolites of 5alpha-dihydrotestosterone. AR activity was
mediated via binding to an estrogen receptor half-site 3' to the FOXA1 and
ERalpha-binding sites. Although AR and FOXA1 bound the UGT promoters in AR
positive/ERalpha-negative breast cancer cell lines, androgen treatment did not
influence basal transcription levels. Ex vivo culture of human breast tissue and
ERalpha+ tumors provided evidence for upregulation of UGT2B15 and UGT2B17 by
estrogen or androgen treatment. ERalpha binding was evident at the promoters of
these genes in a small cohort of primary tumors and distant metastases.
Collectively, these data provide insight into sex steroid receptor-mediated
regulation of androgen-inactivating enzymes in ERalpha+ breast cancer, which may
have subtype-specific consequences for disease progression and outcomes. Cancer
Res; 76(19); 5881-93. (c)2016 AACR.
PMID- 27496707
TI - Cancer-Associated Fibroblasts in Pancreatic Cancer Are Reprogrammed by Tumor
Induced Alterations in Genomic DNA Methylation.
AB - Stromal fibrosis is a prominent histologic characteristic of pancreatic ductal
adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor
microenvironment (TME) to support tumor growth is largely unknown. Here we show
that PDAC cells can induce DNA methylation in cancer-associated fibroblasts
(CAF). Upon direct contact with PDAC cells, DNA methylation of SOCS1 and other
genes is induced in mesenchymal stem cells or in CAF that lack SOCS1 methylation
at baseline. Silencing or decitabine treatment to block the DNA methylation
enzyme DNMT1 inhibited methylation of SOCS1. In contrast, SOCS1 gene methylation
and downregulation in CAF activated STAT3 and induced insulin-like growth factor
1 expression to support PDAC cell growth. Moreover, CAF facilitated methylation
dependent growth of PDAC tumor xenografts in mice. The ability of patient-derived
CAF with SOCS1 methylation to promote PDAC growth was more robust than CAF
without SOCS1 methylation. Overall, our results reveal how PDAC cells can
reprogram CAF to modify tumor-stromal interactions in the TME, which promote
malignant growth and progression. Cancer Res; 76(18); 5395-404. (c)2016 AACR.
PMID- 27496709
TI - Accumulation of MDSC and Th17 Cells in Patients with Metastatic Colorectal Cancer
Predicts the Efficacy of a FOLFOX-Bevacizumab Drug Treatment Regimen.
AB - Host immunity controls the development of colorectal cancer, and chemotherapy
used to treat colorectal cancer is likely to recruit the host immune system at
some level. Athough preclinical studies have argued that colorectal cancer drugs,
such as 5-fluorouracil (5-FU) and oxaliplatin, exert such effects, their
combination as employed in the oncology clinic has not been evaluated. Here, we
report the results of prospective immunomonitoring of 25 metastatic colorectal
cancer (mCRC) patients treated with a first-line combination regimen of 5-FU,
oxaliplatin, and bevacizumab (FOLFOX-bevacizumab), as compared with 20 healthy
volunteers. Before this therapy was initiated, T regulatory cells (Treg), Th17,
and granulocytic myeloid-derived suppressor cells (gMDSC) were increased
significantly in mCRC, but only a high level of gMDSC was associated with a poor
prognosis. Chemotherapy modulated the Treg/Th17 balance by decreasing Treg and
increasing Th17 cell frequency by 15 days after the start of treatment. Increased
Th17 frequency was associated with a poor prognosis. FOLFOX-bevacizumab treatment
elicited a decrease in gMDSC in 15 of 25 patients and was associated with a
better survival outcome. Notably, the gMDSCs that expressed high levels of PD-L1,
CD39, and CD73 exerted a robust immunosuppressive activity, relative to other
myeloid cells present in blood, which could be reversed by blocking the CD39/CD73
and PD-1/PD-L1 axes. Our work underscores the critical prognostic impact of early
modifications in Th17 and gMDSC frequency in mCRC. Furthermore, it provides a
clinical rationale to combine FOLFOX-bevacizumab chemotherapy with inhibitors of
ATP ectonucleotidases and/or anti-PD-1/PD-L1 antibodies to more effectively treat
this disease. Cancer Res; 76(18); 5241-52. (c)2016 AACR.
PMID- 27496704
TI - Beyond conventional antibiotics - New directions for combination products to
combat biofilm.
AB - Medical device related infections are a significant and growing source of
morbidity and mortality. Biofilm formation is a common feature of medical device
infections that is not effectively prevented or treated by systemic antibiotics.
Antimicrobial medical device combination products provide a pathway for local
delivery of antimicrobial therapeutics with the ability to achieve high local
concentrations while minimizing systemic side effects. In this review, we present
considerations for the design of local antimicrobial delivery systems, which can
be facilitated by modeling local pharmacokinetics in the context of the target
device application. In addition to the need for local delivery, a critical
barrier to progress in the field is the need to incorporate agents effective
against biofilm. This article aims to review key properties of antimicrobial
peptides that make them well suited to meet the demands of the next generation of
antimicrobial medical devices, including broad spectrum activity, rapid and
biocidal mechanisms of action, and efficacy against biofilm.
PMID- 27496710
TI - Nestin Mediates Hedgehog Pathway Tumorigenesis.
AB - The intermediate filament protein Nestin serves as a biomarker for stem cells and
has been used to identify subsets of cancer stem-like cells. However, the
mechanistic contributions of Nestin to cancer pathogenesis are not understood.
Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3
to mediate the development of medulloblastomas of the hedgehog subtype. In a
mouse model system, Nestin levels increased progressively during medulloblastoma
formation, resulting in enhanced tumor growth. Conversely, loss of Nestin
dramatically inhibited proliferation and promoted differentiation. Mechanistic
investigations revealed that the tumor-promoting effects of Nestin were mediated
by binding to Gli3, a zinc finger transcription factor that negatively regulates
hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its
subsequent proteolytic processing, thereby abrogating its ability to negatively
regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog
pathway-driven cancers and uncover in Gli3 a therapeutic target to treat these
malignancies. Cancer Res; 76(18); 5573-83. (c)2016 AACR.
PMID- 27496712
TI - PAK4 Phosphorylates p53 at Serine 215 to Promote Liver Cancer Metastasis.
AB - PAK4 kinase contributes to signaling pathways controlling cancer cell
transformation, invasion, and survival, but its clinicopathological impact has
begun to emerge only recently. Here we report that PAK4 overexpression in
hepatocellular carcinoma (HCC) conveys aggressive metastatic properties. A novel
nuclear splice isoform of PAK4 lacking exon 2 sequences was isolated as part of
our studies. By stably overexpressing or silencing PAK4 in HCC cells, we showed
that it was critical for their migration. Mechanistic investigations in this
setting revealed that PAK4 directly phosphorylated p53 at S215, which not only
attenuated transcriptional transactivation activity but also inhibited p53
mediated suppression of HCC cell invasion. Taken together, our results showed how
PAK4 overexpression in HCC promotes metastatic invasion by regulating p53
phosphorylation. Cancer Res; 76(19); 5732-42. (c)2016 AACR.
PMID- 27496711
TI - Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse
Analysis.
AB - Traditional approaches to evaluating antitumor agents using human tumor xenograft
models have generally used cohorts of 8 to 10 mice against a limited panel of
tumor models. An alternative approach is to use fewer animals per tumor line,
allowing a greater number of models that capture greater molecular/genetic
heterogeneity of the cancer type. We retrospectively analyzed 67 agents evaluated
by the Pediatric Preclinical Testing Program to determine whether a single mouse,
chosen randomly from each group of a study, predicted the median response for
groups of mice using 83 xenograft models. The individual tumor response from a
randomly chosen mouse was compared with the group median response using
established response criteria. A total of 2,134 comparisons were made. The single
tumor response accurately predicted the group median response in 1,604
comparisons (75.16%). The mean tumor response correct prediction rate for 1,000
single mouse random samples was 78.09%. Models had a range for correct prediction
(60%-87.5%). Allowing for misprediction of +/- one response category, the overall
mean correct single mouse prediction rate was 95.28%, and predicted overall
objective response rates for group data in 66 of 67 drug studies. For molecularly
targeted agents, occasional exceptional responder models were identified and the
activity of that agent confirmed in additional models with the same genotype.
Assuming that large treatment effects are targeted, this alternate experimental
design has similar predictive value as traditional approaches, allowing for far
greater numbers of models to be used that more fully encompass the heterogeneity
of disease types. Cancer Res; 76(19); 5798-809. (c)2016 AACR.
PMID- 27496713
TI - Zika virus infection: epidemiology, clinical manifestations and diagnosis.
AB - PURPOSE OF REVIEW: Zika virus (ZIKV) is an arbovirus previously believed to cause
only a mild and self-limiting illness. Recently, it has emerged as a new public
health threat that caused a large outbreak in French Polynesia in 2013-2014 and
since 2015 an explosive outbreak in Brazil, with an increase in severe congenital
malformations (microcephaly) and neurological complications, mainly Guillain
Barre syndrome (GBS). Since then, it has spread through the Americas. On 1
February 2016, the WHO declared the ZIKV epidemic in Brazil a Public Health
Emergency of International Concern. We reviewed the epidemiology of ZIKV
infection, clinical presentations and diagnosis. We highlighted the clinical
features and nonvector borne transmission of the virus. RECENT FINDINGS:
Association between ZIKV infection and severe foetal outcomes, including
microcephaly and other birth defects; increased rate of GBS and other
neurological complications due to the ongoing ZIKV outbreak; increased evidence
to date of ZIKV being the only arbovirus linked to sexual transmission; the
challenge of ZIKV diagnosis; and the need for a specific point-of care test in
epidemic scenarios. SUMMARY: The findings illustrate the emergence of a viral
disease with the identification of new associated disorders, new modes of
transmission, including maternal-foetal and sexual transmission.
PMID- 27496714
TI - Perinatal BPA exposure alters body weight and composition in a dose specific and
sex specific manner: The addition of peripubertal exposure exacerbates adverse
effects in female mice.
AB - Body weight (BW) and body composition were examined in CD-1 mice exposed
perinatally or perinatally and peripubertally to 0, 0.25, 2.5, 25, or 250MUg
BPA/kg BW/day. Our goal was to identify the BPA dose (s) and the exposure
window(s) that increased BW and adiposity, and to assess potential sex
differences in this response. Both perinatal exposure alone and perinatal plus
peripubertal exposure to environmentally relevant levels of BPA resulted in
lasting effects on body weight and body composition. The effects were dose
specific and sex specific and were influenced by the precise window of BPA
exposure. The addition of peripubertal BPA exposure following the initial
perinatal exposure exacerbated adverse effects in the females but appeared to
reduce differences in body weight and body composition between control and BPA
exposed males. Some effects of BPA on body weight and body composition showed a
non-linear dose response.
PMID- 27496715
TI - Early-life exposures to persistent organic pollutants in relation to overweight
in preschool children.
AB - Current knowledge on obesogenic effects of persistent organic pollutants (POPs)
is equivocal. We therefore evaluated the associations between early-life POP
exposures and body mass index (BMI) in 444 Faroese children born in 2007-2009.
POPs were measured in maternal 2-week postpartum serum and child age-5 serum.
Linear regression and generalised linear models assessed the associations with
continuous and dichotomous BMI z-scores, respectively, at ages 18 months and/or 5
years. Maternal serum concentrations of HCB, PFOS and PFOA were associated with
increased BMI z-scores and/or overweight risk (i.e. BMI z-score>=85th WHO
percentile). No clear association was found for maternal serum-PCBs, p,p'-DDE,
PFHxS, PFNA and PFDA. In cross-sectional analyses, we observed a pattern of
inverse associations between child serum-POPs and BMI z-scores at age 5, perhaps
due to reverse causation that requires attention in future prospective analyses.
Findings in this recent cohort support a role of maternal exposure to endocrine
disruptors in the childhood obesity epidemic.
PMID- 27496717
TI - Randomized, Prospective Comparison of Bioabsorbable and Steel Screw Fixation of
Lisfranc Injuries.
AB - OBJECTIVE: This study's objective is to compare outcomes of bioabsorbable versus
steel screws for treating Lisfranc injuries. DESIGN: This research was conducted
in a prospective and randomized manner between September 2008 and December 2013.
SETTING: This study was performed in the outpatient setting at a tertiary-level
care center in a single surgeon's practice. PATIENTS/PARTICIPANTS: Forty patients
with acute Lisfranc injuries, amenable to open reduction and screw fixation,
enrolled and presented for final follow-up. INTERVENTION: Through randomization,
20 and 20 patients received bioabsorbable versus steel screws, respectively.
OUTCOME MEASUREMENTS: Function and pain were graded using the Foot and Ankle
Ability Measures (FAAM) and a visual analog scale of pain. Radiographs were
assessed for joint stability and degeneration. RESULTS: For those with steel
screws, the mean FAAM score increased from 24.9 to 89.6 of 100 and pain score
decreased from 6.5 to 1.9 of 10 by latest follow-up. For those with absorbable
screws, the mean FAAM score increased from 32.5 to 91.2 and pain score decreased
from 4.7 to 1.3 by latest follow-up. These differences in final mean function (P
= 0.4) and pain (P = 0.25) between the study groups were not statistically
significant. Final radiographs showed no Lisfranc instability in any study
patients, but rather midfoot arthritis in 4 and 2 patients with steel versus
bioabsorbable screws, respectively. None of the patients who received steel
screws had hardware-related problems, but 1 patient who received absorbable
fixation developed an inflammatory reaction at a nonresorbed screw head at 2
years after surgery. CONCLUSIONS: Bioabsorbable screws provide short-term results
that are comparable and not significantly different from steel screws for
treating unstable Lisfranc injuries. Both methods are predictable in improving
function and pain, but using absorbable screws eliminates the need for hardware
removal after such trauma. LEVEL OF EVIDENCE: Therapeutic Level I. See
Instructions for Authors for a complete description of levels of evidence.
PMID- 27496716
TI - Longitudinal effects of developmental bisphenol A and variable diet exposures on
epigenetic drift in mice.
AB - Environmental factors, including exogenous exposures and nutritional status, can
affect DNA methylation across the epigenome, but effects of exposures on age
dependent epigenetic drift remain unclear. Here, we tested the hypothesis that
early-life exposure to bisphenol A (BPA) and/or variable diet results in altered
epigenetic drift, as measured longitudinally via target loci methylation in
paired mouse tail tissue (3 wks/10 mos old). Methylation was quantified at two
repetitive elements (LINE-1, IAP), two imprinted genes (Igf2, H19), and one non
imprinted gene (Esr1) in isogenic mice developmentally exposed to Control,
Control+BPA (50MUg/kg diet), Mediterranean, Western, Mediterranean+BPA, or
Western+BPA diets. Across age, methylation levels significantly (p<0.050)
decreased at LINE-1, IAP, and H19, and increased at Esr1. Igf2 demonstrated
Western-specific changes in early-life methylation (p=0.027), and IAP showed
marginal negative modification of drift in Western (p=0.058) and Western+BPA
(p=0.051). Thus, DNA methylation drifts across age, and developmental nutritional
exposures can alter age-related methylation patterns.
PMID- 27496719
TI - Factors associated with receiving anti-osteoporosis treatment among older persons
with minimal trauma hip fracture presenting to an acute orthogeriatric service.
AB - BACKGROUND/AIM: The aim of this study was to investigate factors that were
associated with receiving anti-osteoporosis treatment (AOT) among patients with
minimal trauma hip fracture admitted to an Australian tertiary trauma centre
under the Acute Orthogeriatric Service (AOS) over a 6 month period. DESIGN:
Observational study using prospectively collected data. METHODS: Demographic and
clinical characteristics of 211 patients were extracted from the local hip
fracture registry and electronic medical records. The outcome measure was receipt
of AOT before separation from the AOS. Binary logistic regression was used to
identify factors independently associated with treatment. RESULTS: 91 (45%)
patients received AOT, including 51 (25.2%) treatment-naive patients. Factors
significantly associated with receiving treatment included higher serum vitamin D
level (OR 1.44, 95% CI 1.23-1.70, p<0.001) and trochanteric vs. cervical fracture
(OR 2.67, 95% CI 1.30-5.49, p=0.007). Living in a residential aged care facility
(RACF) prior to the index fracture (OR 0.2, 95% CI 0.08-0.54, p=0.001) and higher
American Society of Anaesthesiologists (ASA) physical status score (OR 0.5, 95%
CI 0.25-0.98, p=0.04) significantly lowered the likelihood of treatment. Age,
gender, cognitive impairment, premorbid walking ability, previous fragility
fracture and renal impairment did not correlate with treatment. CONCLUSION: A
significant proportion (55%) of hip fracture patients did not receive AOT in
hospital. The probability of receiving treatment appears to be significantly
associated with serum vitamin D level, fracture type, place of residence and
comorbidity burden.
PMID- 27496718
TI - Hypothesis testing clarifies the systematics of the main Central American Chagas
disease vector, Triatoma dimidiata (Latreille, 1811), across its geographic
range.
AB - The widespread and diverse Triatoma dimidiata is the kissing bug species most
important for Chagas disease transmission in Central America and a secondary
vector in Mexico and northern South America. Its diversity may contribute to
different Chagas disease prevalence in different localities and has led to
conflicting systematic hypotheses describing various populations as subspecies or
cryptic species. To resolve these conflicting hypotheses, we sequenced a nuclear
(internal transcribed spacer 2, ITS-2) and mitochondrial gene (cytochrome b) from
an extensive sampling of T. dimidiata across its geographic range. We evaluated
the congruence of ITS-2 and cyt b phylogenies and tested the support for the
previously proposed subspecies (inferred from ITS-2) by: (1) overlaying the ITS-2
subspecies assignments on a cyt b tree and, (2) assessing the statistical support
for a cyt b topology constrained by the subspecies hypothesis. Unconstrained
phylogenies inferred from ITS-2 and cyt b are congruent and reveal three clades
including two putative cryptic species in addition to T. dimidiata sensu stricto.
Neither the cyt b phylogeny nor hypothesis testing support the proposed
subspecies inferred from ITS-2. Additionally, the two cryptic species are
supported by phylogenies inferred from mitochondrially-encoded genes cytochrome c
oxidase I and NADH dehydrogenase 4. In summary, our results reveal two cryptic
species. Phylogenetic relationships indicate T. dimidiata sensu stricto is not
subdivided into monophyletic clades consistent with subspecies. Based on
increased support by hypothesis testing, we propose an updated systematic
hypothesis for T. dimidiata based on extensive taxon sampling and analysis of
both mitochondrial and nuclear genes.
PMID- 27496720
TI - Which patients risk segmental kyphosis after short segment thoracolumbar fracture
fixation with intermediate screws?
AB - INTRODUCTION: The use of intermediate screws in fractured vertebrae has been
proposed to decrease the number of fused levels in thoracolumbar fractures and to
enable short fixations. The aim of this study was to evaluate the results of this
technique and to establish predictive factors involved in loss of segmental
kyphosis correction (LKC). METHODS: Forty-three patients who underwent short
segment spinal fixation with intermediate screws for a thoracolumbar spine
fracture in a two-year time period were enrolled in the study. Patients had AO
type A3, A4 and B2 thoracolumbar fractures. Radiological parameters included
segmental kyphosis (SK), vertebral wedge angle (VWA) and loss of anterior and
posterior vertebral body height. Patients were evaluated up to one-year follow
up. The correlation between LKC and potential risk factors, such as smoking
habit, sex, age, neurological status and BMI was evaluated. RESULTS: Mean
preoperative SK was 16.5 degrees +/-6.5 degrees , and it decreased to 3.4 degrees
+/-3.5 degrees postoperatively (P<0.01). At the one-year follow-up mean SK
dropped to 5.5 degrees +/-3.9 degrees (P<0.01). Mean preoperative VWA was 20.0
degrees +/-8.1 degrees , and significantly improved to 6.3 degrees +/-3.1 degrees
after surgery (P<0.01). There was a mean LKC of 1.8 degrees +/-2.1 degrees at
one year. LKC mildly correlated with body mass index (BMI, r: +0.31), and obese
patients (BMI>30) had an increased risk of LKC at the one-year follow-up (P=0.03;
odds ratio [OR]=3.2). DISCUSSION: Analysis of the radiological data at one-year
follow-up showed that all the evaluated parameters were associated with a mild
loss of correction, with no impact on the clinical outcomes or implant failure.
These findings confirm the trends reported in the literature. The correlation
between LKC and clinical features, such as BMI, age, sex, smoking habit and
preoperative neurological status was investigated. Interestingly, a positive
correlation was observed between BMI and LKC, and obese patients with BMI>30 had
an increased risk of LKC at one-year follow-up (OR 3.2); to our knowledge this
finding has never before been reported. CONCLUSION: Short-segment fixation with
intermediate screws is a viable technique with positive clinical and radiological
outcomes at one-year follow-up. However, surgeons should be aware that in obese
patients (BMI>30) this technique is associated with an increased risk of LKC.
LEVEL OF EVIDENCE: 3.
PMID- 27496721
TI - The role of sarcopenia with and without fracture.
AB - INTRODUCTION: Bone and muscle tissues are in a close relationship. They are
linked from a biological and functional point of view and both are related to an
increased fracture risk in the elderly. The aging process is involved in the loss
of functionality of both bones and muscles. In particular, aging-induced decline
in muscle size and quality accompanies catabolic alterations in bone tissue;
furthermore, age-related changes in bone alter its response to muscle-derived
stimulation. The increased fracture risk in individuals with sarcopenia and
osteoporosis is due to the decline of muscle mass and strength, the decrease in
bone mineral density (BMD) and limited mobility. In this study, we investigated
the role of sarcopenia and the main age-related bone diseases, osteoporosis (OP)
and osteoarthritis (OA). METHODS: Muscular performance status was evaluated using
the Physical Activity Scale for the Elderly (PASE) test in 27 female patients
with OP who underwent total hip arthroplasty for hip fracture, and in 27 age
matched female patients with OA who underwent total hip arthroplasty. Dual-energy
X-ray absorptiometry (DEXA) was performed and the T-score values were used to
discriminate between OP and OA patients. Body Mass Index (BMI) was calculated. As
part of a multiparametric model of evaluation, biopsies of vastus lateralis
muscle were analysed by immunohistochemical reaction to find a correlation with
the above mentioned functional index. RESULTS: The PASE test showed that the OP
patients had a low or moderate level of physical activity before fracture
occurred, whereas the OA patients had more intensive pre-fracture physical
performances. Histological analysis showed that osteoporosis is characterised by
a preferential type II fibre atrophy; in particular, data correlation showed that
lower PASE test scores were related to lower diameter of type II fibres. No
correlation was found between bone mineral density (BMD) and PASE test results.
DISCUSSION AND CONCLUSION: Osteoporosis is closely related to sarcopenia before
and after fracture. Bone remodelling is influenced by muscle morphological and
functional impairment and sarcopenia is considered one of the major factors for
functional limitation and motor dependency in elderly osteoporotic individuals.
Therefore, physical activity should be strongly recommended for OP patients at
diagnosis.
PMID- 27496722
TI - Cambridge Polytrauma Pathway: Are we making appropriately guided decisions?
AB - Addenbrooke's Hospital, the Major Trauma Centre for the East of England Trauma
Network, received 1070 major trauma patients between 1st January and 31st
December 2014. In order to improve care, an audit was performed of 59 patients
meeting our own selection criteria for orthopaedic polytrauma between 1st January
2013 and 31st December 2013. The Cambridge Polytrauma Pathway was devised through
NCEPOD guidelines, literature review, internal and external discussion. It
facilitates provision of best practice Early Appropriate Care, encompassing -
multidisciplinary consultant decisions around the patient in our Neurological and
Trauma Critical Care Unit, early full body trauma CT scans, serial measurements
of lactate and fibrinogen levels, and out-of-hours orthopaedic theatre reserved
for life-and-limb threatening injuries. Re-audit was conducted of 15 patients
meeting selection criteria, admitted between 1st October 2014 and 31st March
2015. Significant improvements in recording of lactate and fibrinogen were
demonstrated, both on admission (lactate - p<0.000, fibrinogen - p=0.015), and
preoperatively (lactate - p=0.003, fibrinogen - p=0.030). Time to trauma CT was
unchanged (p=0.536) with a median time to CT of 0.53h at re-audit (IQR 0.48
0.75). The number of patients receiving definitive orthopaedic intervention out
of-hours reduced from 8 to zero (p=0.195). The approach of facilitating
management decisions to be made at early daytime MDT meetings has been adopted.
It is anticipated that this pathway will improve outcomes in orthopaedic
polytrauma patients and it is recommended that either the GOS-E, or the EQ-5D
scoring systems be introduced to assess this.
PMID- 27496723
TI - Hertel 7 fracture of the humeral head. Can two different fixation systems
(Diphos/PHP) lead to different outcomes? A retrospective study.
AB - OBJECTIVE: To compare clinical outcomes and complication rates in the medium-to
long-term follow-up of Hertel 7 humeral head fractures treated with two different
locking plates. MATERIALS AND METHODS: A total of 52 patients with type 7 humeral
head fracture (in accordance with Hertel classification) were enrolled
retrospectively: 24 patients [4 male, 20 female; mean age (standard deviation
[SD]): 68.9 (5.8) years] were treated with Diphos H plate (Group A) and 28
patients [6 male, 22 female; mean age (SD): 61.0 (7.5) years] with Proximal
Humeral Plate (PHP; Group B). The mean follow-up periods were 25.6 and 18.9
months, respectively. Functional outcomes were assessed using the Constant score
and Disabilities of the Arm, Shoulder and Hand (DASH) score; X-ray evaluation was
also performed and complications were recorded. RESULTS: The mean Constant score
in the Diphos and PHP groups at follow-up were 75.6 (SD 13.4) and 78.9 (SD 12.8),
respectively (p>0.05). The DASH score was similar in both groups (Diphos: 18.6,
range 0-51.5; PHP: 16.8, range 0-47.8) (p>0.05). In our series, 9.6% of patients
had complications; these included a case of aseptic non-union and a case of
avascular necrosis of the humeral head in each group, and a secondary screw
perforation in a patient treated with Diphos. CONCLUSIONS: In patients with
Hertel 7 proximal humeral fractures, Diphos and PHP lead to similar satisfactory
functional outcomes and are associated with low complication rates; this confirms
that both are useful implants for the treatment of this pattern of fracture.
PMID- 27496724
TI - A feasibility study of pelvic morphology for curved implants.
AB - OBJECTIVES: We hypothesize that inserting a curved intramedullary internal
fixation device which follows curved osseous fixation paths (OFPs) would be more
versatile and mechanically stronger than straight screws for fixation of pelvic
ring and acetabular injuries. This study characterizes the dimensions of curved
OFPs of the pelvic ring and acetabulum and suggests design parameters for such a
curved device. METHODS: CT scans of intact pelves of 50 female and 50 male
subjects were studied using MIM MaestroTM and SolidworksTM to determine the
constriction points (smallest cross sections) and the tightest radii of curvature
(RoC) in the anterior column, posterior column, iliosacral and pubic symphysis
OFPs. RESULTS: The constriction point diameters for the superior pubic ramus and
supra-acetabular areas were 13+/-3mm and 12+/-3mm, respectively. The anterior
column RoC was greater than 65mm in all cases. The minimum observed RoC for the
path from one ilium, across the SI joint, the sacrum and to the other ilium was
71mm, with 99% of the cases having a RoC of at least 80mm, in both the inlet and
outlet views. CONCLUSION: This study shows that if a flexible implant which could
be stiffened once in place was available, it would enable the use of larger and
longer fixation taking advantage of the pelvis's curved intracortical spaces.
Even for dysmorphic pelves, accessible tunnels support a long, strong, curved
fixation device.
PMID- 27496725
TI - Lumboiliac fixation in lumbosacral dislocation and associated injuries of the
pelvis and lumbosacral junction: a long-term radiological and clinical follow-up.
AB - INTRODUCTION: The goal of the study was to evaluate both clinical and
radiological outcome of a consecutive series of 11 patients submitted to
lumboiliac fixation after lumbopelvic disjunction or associated injuries of the
pelvis and lumbosacral tract in mid- and long-term follow-up. MATERIAL AND
METHODS: The following were evaluated from clinical charts: damage control
preoperative procedures, surgery, and pre-, intra- and post-operative
complications; imaging was also evaluated from the preoperative assessment to the
final follow-up (4 to 13.2 years; average 7.2 years). RESULTS: One patient died a
few days after surgery; therefore, long-term follow-up was possible in 10
patients. One of the 10 patients could be evaluated only radiologically because
he was non-compliant due to severe mental illness. There were four early
complications: one patient had a massive pulmonary embolism, which was fatal; one
had wound dehiscence; one developed pulmonary infection and one had caecal
fistula, which was repaired by the general surgeon. Late complications were as
follows: three patients required hardware removal or substitution because of deep
infection (after 1year), system breakage (after 9 years) and screws loosening
(after 7 years). Clinical evaluation was available in nine patients and was
assessed using Oswestry forms and a Visual Analogue Scale (VAS). All patients
were able to walk at least 1 kilometre without external support, two patients
were using pain medication regularly and three patients were classified with
severe disability at final follow-up. Degenerative changes in the joints close to
the fused area were observed in two patients more than 10 years after the
operation, but the correlation with surgery is questionable. DISCUSSION:
Lumbopelvic disjunctions generally follow high-energy trauma often involving
internal thoracic and abdominal organs; therefore, a well-trained team approach
is mandatory to preserve patient life and to provide adequate treatment of
skeletal injuries. Mechanical complications may occur several years after
surgery, thus a long-term follow-up is mandatory. CONCLUSIONS: Lumbopelvic
fixation is an effective surgical technique for treatment of spinopelvic
disjunction. The patient numbers in this series, and in the literature in
general, are low; therefore, a multicentre study is advisable to give evidence
and statistical importance to our findings.
PMID- 27496726
TI - Expression, purification and characterization of Esx-1 secretion-associated
protein EspL from Mycobacterium tuberculosis.
AB - The Esx-1 cluster encodes a special secretion system that is important for
granuloma formation and virulence when Mycobacterium tuberculosis infects the
host. As one of the 'core' genes in the cluster, Rv3880c gene codes an Esx-1
secretion-associated protein EspL from Mycobacterium tuberculosis (MtEspL). It
has been reported that EspL had a strong influence on the secretion of other two
virulence factors, EsxA and EspE. However, so far little is known about the
tertiary structure and specific function of MtEspL due to the difficulty in
preparing the high-quality protein. In this study, we tried several fusion tags
and various expression conditions to recombinantly express MtEspL. Through a four
step purification procedure, ultimately, we successfully prepared the full-length
MtEspL in Escherichia coli BL21 (DE3) with a purity of 98%. The yields of the
purified MtEspL protein were 14 mg/L in Luria Bertani medium and 5.6 mg/L in M9
minimal medium, respectively. Biophysical experiments showed that MtEspL existed
in a dimeric form. Moreover, the (1)H-(15)N HSQC spectrum recorded on MtEspL
illustrates a favorable dispersion of the resonance peaks, indicating that the
symmetric dimeric MtEspL adopted a well-folded structure and might be feasible to
determine its solution structure by NMR spectroscopy. Moreover, we identified a
strong DNA-binding ability of MtEspL with fluorescence quenching experiments. Our
work lays the basis for further structural determination and functional
exploration of MtEspL.
PMID- 27496727
TI - Engineering, expression and purification of a chimeric fibrin-specific
streptokinase.
AB - Streptokinase is a valuable fibrinolytic agent used to cope with myocardial
infarction and brain stroke. Despite its high efficiency in dissolving blood
clots, streptokinase (SK) has no specificity in binding fibrin, causing some
problems such as internal bleedings following its administration. To make
streptokinase fibrin specific and limit the fibrinolytic process to the clot
location, we engineered a chimeric streptokinase by fusing the fibrin binding
Kringle 2 domain of tissue plasminogen activator (TPA) to the streptokinase N
terminal end. The chimeric SK construct (KSK) with inserted Kringle 2 domain was
cloned into pET28a expression vector. The expression of recombinant protein was
carried out in Escherichia coli origami (DE3) and confirmed by SDS-PAGE and
Western blotting analyses. We used the chromogenic substrate S-2251 method to
assess the specific activities of the chimeric and control wild-type proteins.
Then, the two proteins were added in amounts with equal activity to fibrin clots
of identical size. Finally, the supernatant above the fibrin clots was collected
and subjected to the chromogenic assay to analyze the specificity of the chimeric
protein. The specific activities of the chimeric and wild-type proteins were
found to be 0.06 U/mg and 0.07 U/mg, respectively. Because of the binding of the
chimeric protein to fibrin, the mean specific activity was significantly lower in
the KSK supernatant (0.01) compared with the control (approximately 0.06) (p <
0.05). Our in vitro results indicate that the chimeric streptokinase protein has
strong fibrin-specific activity compared to the wild-type protein. However,
further in vivo studies are needed to evaluate its potential fibrinolytic
effects.
PMID- 27496728
TI - Cloning, expression and characterization of potential immunogenic recombinant
hemagglutinin-neuraminidase protein of Porcine rubulavirus.
AB - Blue eye disease caused by Porcine rubulavirus (PorPV) is an endemic viral
infection of swine causing neurological and respiratory disease in piglets, and
reproductive failure in sows and boars. The hemagglutinin-neuraminidase (HN)
glycoprotein of PorPV is the most abundant component in the viral envelope and
the main target of the immune response in infected animals. In this study, we
expressed the HN-PorPV-recombinant (rHN-PorPV) protein in an Escherichia coli
system and analyzed the immune responses in mice. The HN gene was cloned from the
reference strain PorPV-La Piedad Michoacan Virus (GenBank accession number
BK005918), into the pDual expression vector. The expressed protein was identified
at a molecular weight of 61.7 kDa. Three-dimensional modeling showed that the
main conformational and functional domains of the rHN-PorPV protein were
preserved. The antigenicity of the expressed protein was confirmed by Western
blot with a monoclonal antibody recognizing the HN, and by testing against serum
samples from pigs experimentally infected with PorPV. The immunogenicity of the
rHN-PorPV protein was tested by inoculation of BALB/c mice with AbISCO-100((r))
as adjuvant. Analysis of the humoral immune responses in mice showed an increased
level of specific antibodies 14 days after the first immunization, compared to
the control group (P < 0.0005). The results show the ability of the rHN-PorPV
protein to induce an antibody response in mice. Due to its immunogenic potential,
the rHN-PorPV protein will be further evaluated in pig trials for its suitability
for prevention and control of blue eye disease.
PMID- 27496729
TI - Bioenergetic Insufficiencies Due to Metabolic Alterations Regulated by the
Inhibitory Receptor PD-1 Are an Early Driver of CD8(+) T Cell Exhaustion.
AB - Dynamic reprogramming of metabolism is essential for T cell effector function and
memory formation. However, the regulation of metabolism in exhausted CD8(+) T
(Tex) cells is poorly understood. We found that during the first week of chronic
lymphocytic choriomeningitis virus (LCMV) infection, before severe dysfunction
develops, virus-specific CD8(+) T cells were already unable to match the
bioenergetics of effector T cells generated during acute infection. Suppression
of T cell bioenergetics involved restricted glucose uptake and use, despite
persisting mechanistic target of rapamycin (mTOR) signaling and upregulation of
many anabolic pathways. PD-1 regulated early glycolytic and mitochondrial
alterations and repressed transcriptional coactivator PGC-1alpha. Improving
bioenergetics by overexpression of PGC-1alpha enhanced function in developing Tex
cells. Therapeutic reinvigoration by anti-PD-L1 reprogrammed metabolism in a
subset of Tex cells. These data highlight a key metabolic control event early in
exhaustion and suggest that manipulating glycolytic and mitochondrial metabolism
might enhance checkpoint blockade outcomes.
PMID- 27496730
TI - Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education
Programmed by Cell-Intrinsic MHC Class I.
AB - The effector potential of NK cells is counterbalanced by their sensitivity to
inhibition by "self" MHC class I molecules in a process called "education." In
humans, interactions between inhibitory killer immunoglobulin-like receptors
(KIR) and human MHC (HLA) mediate NK cell education. In HLA-B(*)27:05(+)
transgenic mice and in patients undergoing HLA-mismatched hematopoietic cell
transplantation (HCT), NK cells derived from human CD34(+) stem cells were
educated by HLA from both donor hematopoietic cells and host stromal cells.
Furthermore, mature human KIR3DL1(+) NK cells gained reactivity after adoptive
transfer to HLA-B(*)27:05(+) mice or bone marrow chimeric mice where HLA
B(*)27:05 was restricted to either the hematopoietic or stromal compartment.
Silencing of HLA in primary NK cells diminished NK cell reactivity, while
acquisition of HLA from neighboring cells increased NK cell reactivity.
Altogether, these findings reveal roles for cell-extrinsic HLA in driving NK cell
reactivity upward, and cell-intrinsic HLA in maintaining NK cell education.
PMID- 27496731
TI - The AIM2-like Receptors Are Dispensable for the Interferon Response to
Intracellular DNA.
AB - Detection of intracellular DNA triggers activation of the STING-dependent
interferon-stimulatory DNA (ISD) pathway, which is essential for antiviral
responses. Multiple DNA sensors have been proposed to activate this pathway,
including AIM2-like receptors (ALRs). Whether the ALRs are essential for
activation of this pathway remains unknown. To rigorously explore the function of
ALRs, we generated mice lacking all 13 ALR genes. We found that ALRs are
dispensable for the type I interferon (IFN) response to transfected DNA ligands,
DNA virus infection, and lentivirus infection. We also found that ALRs do not
contribute to autoimmune disease in the Trex1(-/-) mouse model of Aicardi
Goutieres Syndrome. Finally, CRISPR-mediated disruption of the human AIM2-like
receptor IFI16 in primary fibroblasts revealed that IFI16 is not essential for
the IFN response to human cytomegalovirus infection. Our findings indicate that
ALRs are dispensable for the ISD response and suggest that alternative functions
for these receptors should be explored.
PMID- 27496732
TI - The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive
Intratumoral T Cell Metabolic Insufficiency and Dysfunction.
AB - Although tumor-specific T cells recognize cancer cells, they are often rendered
dysfunctional due to an immunosuppressive microenvironment. Here we showed that T
cells demonstrated persistent loss of mitochondrial function and mass when
infiltrating murine and human tumors, an effect specific to the tumor
microenvironment and not merely caused by activation. Tumor-infiltrating T cells
showed a progressive loss of PPAR-gamma coactivator 1alpha (PGC1alpha), which
programs mitochondrial biogenesis, induced by chronic Akt signaling in tumor
specific T cells. Reprogramming tumor-specific T cells through enforced
expression of PGC1alpha resulted in superior intratumoral metabolic and effector
function. Our data support a model in which signals in the tumor microenvironment
repress T cell oxidative metabolism, resulting in effector cells with metabolic
needs that cannot be met. Our studies also suggest that modulation or
reprogramming of the altered metabolism of tumor-infiltrating T cells might
represent a potential strategy to reinvigorate dysfunctional T cells for cancer
treatment.
PMID- 27496733
TI - ARC Syndrome-Linked Vps33B Protein Is Required for Inflammatory Endosomal
Maturation and Signal Termination.
AB - Toll-like receptors (TLRs) and other pattern-recognition receptors (PRRs) sense
microbial ligands and initiate signaling to induce inflammatory responses.
Although the quality of inflammatory responses is influenced by internalization
of TLRs, the role of endosomal maturation in clearing receptors and terminating
inflammatory responses is not well understood. Here, we report that Drosophila
and mammalian Vps33B proteins play critical roles in the maturation of phagosomes
and endosomes following microbial recognition. Vps33B was necessary for clearance
of endosomes containing internalized PRRs, failure of which resulted in enhanced
signaling and expression of inflammatory mediators. Lack of Vps33B had no effect
on trafficking of endosomes containing non-microbial cargo. These findings
indicate that Vps33B function is critical for determining the fate of signaling
endosomes formed following PRR activation. Exaggerated inflammatory responses
dictated by persistence of receptors in aberrant endosomal compartments could
therefore contribute to symptoms of ARC syndrome, a disease linked to loss of
Vps33B.
PMID- 27496735
TI - Use of microextraction by packed sorbent directly coupled to an electron
ionization single quadrupole mass spectrometer as an alternative for non
separative determinations.
AB - Sometimes it is not necessary to separate the individual compounds of a sample to
resolve an analytical problem, it is enough to obtain a signal profile of the
sample formed by all the components integrating it. Within this strategy,
electronic noses based on the direct coupling of a headspace sampler with a mass
spectrometer (HS-MS) have been proposed. Nevertheless, this coupling is not
suitable for the analysis of non-volatile compounds. In order to propose an
alternative to HS-MS determinations for non-volatile compounds, here we present
the first 'proof of concept' use of the direct coupling of microextraction by
packed sorbents (MEPS) to a mass spectrometer device using an electron ionization
(EI) and a single quadrupole as ionization source and analyzer, respectively. As
target compounds, a set of analytes with different physic-chemical properties
were evaluated (2-ethyl-1-hexanol, styrene, 2-heptanone, among others). The use
of MEPS extraction present many advantages, such as it is fast, simple, easy to
automate and requires small volumes of sample and organic solvents. Moreover,
MEPS cartridges are re-usable as samples can be extracted more than 100 times
using the same syringe. In order to introduce into the system all the elution
volume from the MEPS extraction, a programmable temperature vaporizer (PTV) is
proposed as the injector device. Results obtained with the proposed methodology
(MEPS-PTV/MS) were compared with the ones obtained based on the separative
scheme, i.e. using gas chromatography separation (MEPS-PTV-GC/MS), and both
methods provided similar results. Limits of detection were found to be between
3.26 and 146.6MUgL-1 in the non-separative scheme and between 0.02 and 1.72MUgL-1
when the separative methodology was used. Repeatability and reproducibility were
evaluated with values below 17% in all cases.
PMID- 27496736
TI - Intratumoral FoxP3 expression is associated with angiogenesis and prognosis in
malignant canine mammary tumors.
AB - The activity of regulatory T cells (Tregs) is closely associated with the
expression of FoxP3 transcription factor. FoxP3 regulatory T cells (FoxP3Treg)
have immunosuppressive properties and can work for prevention of harmful
autoimmune responses, however can also interfere with beneficial anti-tumor
immunity. In human breast cancer these cells play a crucial role in tumor
progression. In canine mammary tumors (CMT) this topic is not well-documented.
This study included 80 malignant CMT and studied, by immunohistochemistry, the
intratumoral FoxP3 expression together with microvessel density (MVD), vascular
endothelial growth factor (VEGF) and several clinicopathological characteristics.
Abundant FoxP3Treg cells were associated with tumor necrosis (p=0.001), high
mitotic grade (p<0.001), more marked nuclear polymorphism (p=0.001), poor
differentiation of tumors (p<0.001), high histological grade of malignancy (HGM)
(p<0.001), presence of neoplastic intravascular emboli (p<0.001) and presence of
lymph node metastasis (p<0.001). Intratumoral FoxP3 was correlated with MVD
(r=0.827; p<0.001) and associated with VEGF (p=0.001). Additionally tumors with
abundant FoxP3Treg cells were associated with shorter overall survival (OS) time
in univariate and multivariate analysis (p<0.001 Kaplan-Meier curves and 7.97
hazard ratio, p<0.001 Cox proportional hazard model). Results suggest that Treg
cells play a role in CMT progression and may contribute to increased angiogenesis
and aggression in these tumors. The association of intratumoral FoxP3 expression
with shorter OS in multivariate analysis suggests the usefulness of Treg cells as
an independent prognostic marker.
PMID- 27496734
TI - Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin
Resistance.
AB - Innate lymphoid cells (ILCs) function to protect epithelial barriers against
pathogens and maintain tissue homeostasis in both barrier and non-barrier
tissues. Here, utilizing Eomes reporter mice, we identify a subset of adipose
group 1 ILC (ILC1) and demonstrate a role for these cells in metabolic disease.
Adipose ILC1s were dependent on the transcription factors Nfil3 and T-bet but
phenotypically and functionally distinct from adipose mature natural killer (NK)
and immature NK cells. Analysis of parabiotic mice revealed that adipose ILC1s
maintained long-term tissue residency. Diet-induced obesity drove early
production of interleukin (IL)-12 in adipose tissue depots and led to the
selective proliferation and accumulation of adipose-resident ILC1s in a manner
dependent on the IL-12 receptor and STAT4. ILC1-derived interferon-gamma was
necessary and sufficient to drive proinflammatory macrophage polarization to
promote obesity-associated insulin resistance. Thus, adipose-resident ILC1s
contribute to obesity-related pathology in response to dysregulated local
proinflammatory cytokine production.
PMID- 27496737
TI - Feeding a high dosage of zinc oxide affects suppressor of cytokine gene
expression in Salmonella Typhimurium infected piglets.
AB - Suppressor of cytokine signaling (SOCS) proteins play an important role in the
regulation of the immune response by inhibiting cytokines. Here we investigated
the effects of zinc oxide fed at three different dosages (LZN=57ppm, MZN=167ppm,
HZN=2425ppm) to weaned piglets that were or were not orally infected with
Salmonella enterica serovar Typhimurium DT 104. We detected higher expression of
SOCS3 six days after weaning for all analyzed piglets, regardless of the
infection or the zinc feeding, suggesting a stress induced immune response.
Whereas, SOCS1 showed only higher transcript amounts in S. Typhimurium infected
piglets, especially the LZN group. This might indicate an infection regulating
effect of zinc oxide in the infection model. After 42days of infection, the
expression of SOCS2, SOCS4, and SOCS7 was increased only in animals fed the
highest concentrations of zinc oxide, while non-infected piglets at the age of
56days showed no regulation for these genes. The up-regulation of SOCS genes in
the mesenteric lymph nodes of piglets fed a diet with a very high concentration
of zinc over 6 weeks suggests that such treatments may impair the immune
response.
PMID- 27496738
TI - Comparative analysis of the immunologic response induced by the Sterne 34F2 live
spore Bacillus anthracis vaccine in a ruminant model.
AB - The Sterne 34F2 live spore vaccine (SLSV) developed in 1937 is the most widely
used veterinary vaccine against anthrax. However, literature on the
immunogenicity of this vaccine in a target ruminant host is scarce. In this
study, we evaluated the humoral response to the Bacillus anthracis protective
antigen (rPA), a recombinant bacillus collagen-like protein of anthracis (rBclA),
formaldehyde inactivated spores (FIS) prepared from strain 34F2 and a vegetative
antigen formulation prepared from a capsule and toxin deficient strain (CDC 1014)
in Boer goats. The toxin neutralizing ability of induced antibodies was evaluated
using an in vitro toxin neutralization assay. The protection afforded by the
vaccine was also assessed in vaccinates. Anti-rPA, anti-FIS and lethal toxin
neutralizing titres were superior after booster vaccinations, compared to single
vaccinations. Qualitative analysis of humoral responses to rPA, rBclA and FIS
antigens revealed a preponderance of anti-FIS IgG titres following either single
or double vaccinations with the SLSV. Antibodies against FIS and rPA both
increased by 350 and 300-fold following revaccinations respectively. There was no
response to rBclA following vaccinations with the SLSV. Toxin neutralizing titres
increased by 80-fold after single vaccination and 700-fold following a double
vaccination. Lethal challenge studies in naive goats indicated a minimum
infective dose of 36 B. anthracis spores. Single and double vaccination with the
SLSV protected 4/5 and 3/3 of goats challenged with>800 spores respectively. An
early booster vaccination following the first immunization is suggested in order
to achieve a robust immunity. Results from this study indicate that this crucial
second vaccination can be administered as early as 3 months after the initial
vaccination.
PMID- 27496739
TI - The effect of hypothermia on influx of leukocytes in the digital lamellae of
horses with oligofructose-induced laminitis.
AB - Sepsis-related laminitis (SRL) is a common complication in the septic/endotoxemic
critically-ill equine patient, in which lamellar injury and failure commonly lead
to crippling distal displacement of the distal phalanx. Similar to organ injury
in human sepsis, lamellar injury in SRL has been associated with inflammatory
events, including the influx of leukocytes into the lamellar tissue and markedly
increased expression of a wide array of inflammatory mediators at the onset of
Obel grade 1 (OG1) laminitis. The only treatment reported both clinically and
experimentally to protect the lamellae in SRL, local hypothermia ("cryotherapy"),
has been demonstrated to effectively inhibit lamellar expression of multiple
inflammatory mediators when initiated at the time of administration of a
carbohydrate overload in experimental models of SRL. However, the effect of
hypothermia on leukocyte influx into affected tissue has not been assessed. We
hypothesized that cryotherapy inhibits leukocyte emigration into the digital
lamellae in SRL. Immunohistochemical staining using leukocyte markers MAC387
(marker of neutrophils, activated monocytes) and CD163 (monocyte/macrophage
specific marker) was performed on archived lamellar tissue samples from an
experimental model of SRL in which one forelimb was maintained at ambient
temperature (AMB) and one forelimb was immersed in ice water (ICE) immediately
following enteral oligofructose administration (10g/kg, n=14 horses). Lamellae
were harvested at 24h post-oligofructose administration (DEV, n=7) or at the
onset of OG1 laminitis (OG1, n=7). Both MAC387-positive and CD163-positive cells
were counted by a single blinded investigator on images [n=10 (40* fields/digit
for MAC387 and 20x fields/digit for CD163)] obtained using Aperio microscopy
imaging analysis software. Data were assessed for normality and analyzed with a
paired t-test and one-way ANOVA with significance set at p<0.05. MAC387-positive
cells were present in low numbers in the lamellar tissue and were decreased in
the hypothermic limbs (vs. AMB limbs, p<0.05) in the OG1 group; no change in
CD163-positive cell numbers was noted across the conditions of the model. This
study demonstrated that hypothermia of the distal limbs instituted early in the
disease process in the horse at risk of SRL significantly attenuates the increase
of MAC387-positive leukocytes in the digital lamellae, but has minimal effect on
increases in lamellar concentrations of the major leukocyte cell type present in
that tissue, CD163-positive mononuclear cells.
PMID- 27496740
TI - Effects of rearing environment on the gut antimicrobial responses of two broiler
chicken lines.
AB - To reduce the risk of enteric disease in poultry, knowledge of how bird gut
innate defences mature with age while also responding to different rearing
environments is necessary. In this study the gut innate responses of two
phylogenetically distinct lines of poultry raised from hatch to 35days, in
conditions mimicing high hygiene (HH) and low hygiene (LH) rearing environments,
were compared. Analyses focussed on the proximal gut antimicrobial activities and
the duodenal and caecal AvBD1, 4 and 10 defensin profiles. Variability in
microbial killing was observed between individual birds in each of the two lines
at all ages, but samples from day 0 birds (hatch) of both lines exhibited marked
killing properties, Line X: 19+/-11% (SEM) and Line Y: 8.5+/-12% (SEM). By day 7
a relaxation in killing was observed with bacterial survival increased from 3
(Line Y (LY)) to 11 (Line X (LX)) fold in birds reared in the HH environment. A
less marked response was observed in the LH environment and delayed until day 14.
At day 35 the gut antimicrobial properties of the two lines were comparable. The
AvBD 1, 4 and 10 data relating to the duodenal and caecal tissues of day 0, 7 and
35 birds LX and LY birds revealed gene expression trends specific to each line
and to the different rearing environments although the data were confounded by
inter-individual variability. In summary elevated AvBD1 duodenal expression was
detected in day 0 and day 7 LX, but not LY birds, maintained in LH environments;
Line X and Y duodenal AvBD4 profiles were detected in day 7 birds reared in both
environments although duodenal AvBD10 expression was less sensitive to bird age
and rearing background. Caecal AvBD1 expression was particularly evident in newly
hatched birds. These data suggest that proximal gut antimicrobial activity is
related to the bird rearing environments although the roles of the AvBDs in such
activities require further investigation.
PMID- 27496741
TI - Generation and characterization of RAG2 knockout pigs as animal model for severe
combined immunodeficiency.
AB - Pigs with severe combined immunodeficiency (SCID) are versatile animal models for
human medical research because of their biological similarities to humans,
suitable body size, and longevity for practical research. SCID pigs with defined
mutation(s) can be an invaluable tool for research on porcine immunity. In this
study, we produced RAG2-knockout pigs via somatic cell nuclear transfer and
analyzed their phenotype. The V(D)J recombination processes were confirmed as
being inactivated. They consistently lacked mature T and B cells but had
substantial numbers of cells considered to be T- or B-cell progenitors as well as
NK cells. They also lacked thymic medulla and lymphoid aggregations in the
spleen, mesenteric lymph nodes, and ileal Peyer's patches. We showed more severe
immunological defects in the RAG2 and IL2RG double-knockout pig through this
study. Thus, SCID pigs could be promising animal models not only for
translational medical research but also for immunological studies of pigs
themselves.
PMID- 27496742
TI - Immune response induced by conjunctival immunization with polymeric antigen
BLSOmp31 using a thermoresponsive and mucoadhesive in situ gel as vaccine
delivery system for prevention of ovine brucellosis.
AB - Control of ovine brucellosis with subcellular vaccines can solve some drawbacks
associated with the use of Brucella melitensis Rev.1. Previous studies have
demonstrated that the polymeric antigen BLSOmp31 administered by parenteral route
was immunogenic and conferred significant protection against B. ovis in rams.
Immunization with BLSOmp31 by conjunctival route could be efficient for the
induction of mucosal and systemic immune responses. In this work, we evaluated
the conjunctival immunization using a thermoresponsive and mucoadhesive in situ
gel composed of Poloxamer 407 (P407) and chitosan (Ch) as vaccine delivery system
for BLSOmp31 in rams. Serum samples, saliva, lacrimal, preputial and nasal
secretions were analyzed to measure specific IgG and IgA antibodies. Cellular
immune response was evaluated in vivo and in vitro. Immunization with BLSOmp31
P407-Ch induced high IgG antibody levels in serum and preputial secretions which
remained at similar levels until the end of the experiment. Levels of IgG in
saliva, lacrimal and nasal secretions were also higher compared to unvaccinated
control group but decreased more rapidly. IgA antibodies were only detected in
nasal and preputial secretions. BLSOmp31-P407-Ch stimulated a significant
cellular immune response in vivo and in vitro. The induction of systemic and
local immune responses indicates a promising potential of P407-Ch for the
delivery of BLSOmp31 by conjunctival route.
PMID- 27496743
TI - Characterization and use of new monoclonal antibodies to CD11c, CD14, and CD163
to analyze the phenotypic complexity of ruminant monocyte subsets.
AB - The sequencing of the bovine genome and development of mass spectrometry, in
conjunction with flow cytometry (FC), have afforded an opportunity to complete
the characterization of the specificity of monoclonal antibodies (mAbs), only
partially characterized during previous international workshops focused on
antibody development for livestock (1991, Leukocyte Antigens in Cattle, Sheep,
and Goats; 1993, Leukocyte Antigens of Cattle and Sheep; 1996, Third Workshop on
Ruminant Leukocyte Antigens). The objective of this study was to complete the
characterization of twelve mAbs incompletely characterized during the workshops
that reacted with molecules predominantly expressed on bovine monocytes and use
them to provide further information on the phenotypic complexity of monocyte
subsets in ruminants. Analysis revealed that the mAbs could be grouped into three
clusters that recognize three different molecules: CD11c, CD14, and CD163.
Following characterization, comparison of the patterns of expression of CD14 and
CD163 with expression of CD16, CD172a, and CD209 revealed the mononuclear cell
population is comprised of multiple subsets with differential expression of these
molecules. Further analysis revealed the epitopes recognized by mAbs to CD14 and
CD163 are conserved on orthologues in sheep and goats. In contrast to CD14 that
is also expressed on sheep and goat granulocytes, CD163 is a definitive marker
for their monocytes.
PMID- 27496744
TI - Capsular polysaccharide from Mycoplasma mycoides subsp. mycoides shows potential
for protection against contagious bovine pleuropneumonia.
AB - Contagious Bovine Pleuropneumonia (CBPP) is a severe respiratory disease caused
by Mycoplasma mycoides subsp. mycoides (Mmm) which is widespread in Africa. The
capsule polysaccharide (CPS) of Mmm is one of the few identified virulence
determinants. In a previous study, immunization of mice against CPS generated
antibodies, but they were not able to prevent multiplication of Mmm in this model
animal. However, mice cannot be considered as a suitable animal model, as Mmm
does not induce pathology in this species. Our aim was to induce antibody
responses to CPS in cattle, and challenge them when they had specific CPS
antibody titres similar or higher than those from cattle vaccinated with the live
vaccine. The CPS was linked to the carrier protein ovalbumin via a carbodiimide
mediated condensation with 1-ethyl-3(3-imethylaminopropyl) carbodiimide (EDC).
Ten animals were immunized twice and challenged three weeks after the booster
inoculation, and compared to a group of challenged non-immunized cattle. When
administered subcutaneously to adult cattle, the vaccine elicited CPS-specific
antibody responses with the same or a higher titre than animals vaccinated with
the live vaccine. Pathology in the group of immunized animals was significantly
reduced (57%) after challenge with Mmm strain Afade compared to the non-immunized
group, a figure in the range of the protection provided by the live vaccine.
PMID- 27496745
TI - Natural autoantibodies in Bos taurus calves during the first twelve weeks of
life.
AB - Natural autoantibodies (NAAb) have a role in maintaining physiological
homeostasis and prevention of infections, and have been found in mammalian
species tested so far. Albeit NAAb levels rise with age, little is known about
the origin, function, regulation and initiation of NAAb in young animals. The
present study addressed the presence of IgM and IgG NAAb binding glutamate
dehydrogenase (GD), carbonic anhydrase (CA), myosin (MYO) and transferrin (TRANS)
from before drinking colostrum until the first 12 weeks of life in plasma of
female calves. In addition, NAAb to these four self-antigens were also measured
in colostrum and in plasma of their mothers during three weeks before calving.
Titers of NAAb binding GD, CA, MYO and TRANS were detected in plasma of cows
before calving, in colostrum, and in plasma of calves before and after drinking
of colostrum. Levels of NAAb in colostrum were positively related with levels of
NAAb in plasma of cows. Before colostrum intake, levels of NAAb in plasma of
calves were not related with levels of NAAb in plasma of their mother but were
influenced by parity of their mother. After colostrum intake, levels of NAAb in
plasma of calves in the first week of life were positively related with levels of
NAAb in colostrum. Low NAAb levels in colostrum were related with low NAAb in
plasma of calves in the first week of life, but after two weeks of life the
relation between colostrum and plasma of calves was absent. In conclusion, NAAb
are already present in the unborn calf, and levels of neonatal NAAb during the
early weeks of life are affected by levels of maternal NAAb obtained via
colostrum.
PMID- 27496746
TI - Production a monoclonal antibody specific to granulocytes of swimming crab
(Portunus trituberculatus) and its cross reactivity with other crustaceans.
AB - In this study, a monoclonal antibody (mAb) 3F4 specific to granulocytes of
swimming crab, Portunus trituberculatus, was obtained by immunizing mice with
whole haemocytes. mAb 3F4 showed strong immunofluorescent reaction with
granulocytes, but no reaction with hyalinocytes. The positive cell percentage of
granulocytes was 86.3% detected by Flow cytometry (FCM). A special antigen with
molecular weight of about 26kDa was further recognized by mAb 3F4 in haemocytes
of P. trituberculatus. mAb 3F4 also showed strong cross-reactivity with
haemocytes of Eriocheir sinensis and Petalomera japonica, but no reaction with
other crustaceans tested. In E. sinensis, the positive cell percentage was 73.4%
for granulocytes and 59.8% for hyalinocytes; while in P. japonica, the positive
cell percentage was 81.2% for granulocytes and 7.1% for hyalinocytes. There was
also a special antigen with molecular weight of about 31kDa identified by mAb 3F4
in haemocytes of E.sinensis, but no corresponding protein band in P. japonica
haemocytes. These results demonstrated that mAb 3F4 can be used as a marker for
granulocytes of crabs.
PMID- 27496747
TI - Effects of injectable trace minerals on humoral and cell-mediated immune
responses to Bovine viral diarrhea virus, Bovine herpes virus 1 and Bovine
respiratory syncytial virus following administration of a modified-live virus
vaccine in dairy calves.
AB - Our objective was to evaluate the effect of an injectable trace mineral (ITM)
supplement containing zinc, manganese, selenium, and copper on the humoral and
cell mediated immune (CMI) responses to vaccine antigens in dairy calves
receiving a modified-live viral (MLV) vaccine containing BVDV, BHV1, PI3V and
BRSV. A total of 30 dairy calves (3.5 months of age) were administered a priming
dose of the MLV vaccine containing BHV1, BVDV1 & 2, BRSV, PI3V, and an attenuated
live Mannheimia-Pasteurella bacterin subcutaneously (SQ). Calves were randomly
assigned to 1 of 2 groups: (1) administration of ITM SQ (ITM, n=15) or (2)
injection of sterile saline SQ (Control; n=15). Three weeks later, calves
received a booster of the same vaccine combination SQ, and a second
administration of ITM, or sterile saline, according to the treatment group. Blood
samples were collected on days 0, 7, 14, 21, 28, 42, 56, and 90 post-vaccination
for determination of antibody titer, viral recall antigen-induced IFN-gamma
production, and viral antigen-induced proliferation by peripheral blood
mononuclear cells (PBMC). Administration of ITM concurrently with MLV vaccination
resulted in higher antibody titers to BVDV1 on day 28 after priming vaccination
compared to the control group (P=0.03). Calves treated with ITM showed an earlier
enhancement in PBMC proliferation to BVDV1 following vaccination compared to the
control group. Proliferation of PBMC after BVDV stimulation tended to be higher
on day 14 after priming vaccination in calves treated with ITM than in the
control group (P=0.08). Calves that received ITM showed higher PBMC proliferation
to BRSV stimulation on day 7 after priming vaccination compared to the control
group (P=0.01). Moreover, calves in the ITM group also had an enhanced production
IFN-gamma by PBMC after stimulation with BRSV on day 21 after priming vaccination
compared to day 0 (P<0.01). In conclusion, administration of ITM concurrently
with MLV vaccination in dairy calves resulted in increased antibody titer to
BVDV1, and greater PBMC proliferation to BVDV1 and BRSV recall stimulation
compared to the control group, suggesting that ITM might represent a promising
tool to enhance the humoral and CMI responses to MLV vaccines in cattle.
PMID- 27496748
TI - Nasal delivery of chitosan-coated poly(lactide-co-glycolide)-encapsulated
honeybee (Apis mellifera) venom promotes Th 1-specific systemic and local
intestinal immune responses in weaned pigs.
AB - Nasal delivery is a convenient and acceptable route for drug administration, and
has been shown to elicit a much more potent local and systemic response compared
with other drug delivery routes. We previously demonstrated that rectal
administration of poly(lactide-co-glycolide)-encapsulated honeybee venom (P-HBV)
could enhance systemic Th 1-specific immune responses. We therefore synthesized
chitosan-coated P-HBV (CP-HBV) and then evaluated the immune-boosting efficacy of
nasally administered CP-HBV on systemic and local intestinal immunity compared
with non-chitosan-coated P-HBV. The nasally delivered CP-HBV effectively enhanced
Th 1-specific responses, eliciting a significant increase in the CD3(+)CD4(+)CD8(
) Th cell population, lymphocyte proliferation capacity, and expression of Th 1
cytokines (IFN-gamma, IL-12, and IL-2) in peripheral blood mononuclear cells.
Furthermore, these immune-boosting effects persisted up to 21days post CP-HBV
administration. Nasal administration of CP-HBV also led to an increase of not
only the CD4(+) Th 1 and IFN-gamma secreting CD4(+) Th 1 cell population but also
Th 1-specific cytokines and transcription factors, including IL-12, IFN-gamma,
STAT4, and T-bet, in isolated mononuclear cells from the spleen and ileum.
PMID- 27496749
TI - Cluster of ulceroglandular tularemia cases in Slovenia.
AB - In Slovenia, a small Central European country, where tularemia cases are very
rare and mostly sporadic, six cases of ulceroglandular tularemia were recognised
in 2012-2013 in patients residing in or visiting a small geographical area of
<6km2. Epidemiological data indicated transmission by a tick bite in at least 3/6
patients.
PMID- 27496750
TI - Breath-print analysis by e-nose may refine risk stratification for adverse
outcomes in cirrhotic patients.
AB - BACKGROUND & AIMS: The spectrum of volatile organic compounds in the exhaled
breath (breath-print, BP) has been shown to characterize patients with cirrhosis
and with worse hepatic function. However, the association of different BPs with
clinically relevant outcomes has not been described yet. Hence, we aimed to
evaluate the association between BPs, mortality and hospitalization in cirrhotic
patients and to compare it with that of the "classical" prognostic indices (Child
Pugh Classification [CPC] and MELD). METHODS: Eighty-nine cirrhotic patients (M/F
59/30, mean age 64.8 +/- 11.3, CPC A/B/C 37/33/19) were recruited and followed up
for a median time of 23 months. Clinical and biochemical data were collected.
Breath collection and analysis were obtained through Pneumopipe(r) and BIONOTE e
nose respectively. RESULTS: Four different BP clusters (A, B, C, D) were
identified. BP clusters A and D were associated with a significantly increased
risk of mortality (HR 2.9, 95% confidence intervals [CI] 1.5-5.6) and
hospitalization (HR 2.6, 95% CI 1.4-4.6), even in multiple adjusted models
including CPC and MELD score (adjusted [a]HR 2.8, 95% CI 1.1-7.0 for mortality
and aHR 2.2, 95% CI 1.1-4.2 for hospitalization). CPC C maintained the strongest
association with both mortality (aHR 17.6, 95% CI 1.8-174.0) and hospitalization
(aHR 12.4, 95% CI 2.0-75.8). CONCLUSIONS: This pilot study demonstrates that BP
clusters are associated with significant clinical endpoints (mortality and
hospitalization) even independently from "classical" prognostic indices. Even
though further studies are warranted on this topic, our findings suggest that the
e-nose may become an adjunctive aid to stratify the risk of adverse outcomes in
cirrhotic patients.
PMID- 27496751
TI - Targeting factor VIII expression to platelets for hemophilia A gene therapy does
not induce an apparent thrombotic risk in mice.
AB - : Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in
hemophilia A. This study aims to evaluate if platelet-FVIII expression would
increase the risk for thrombosis. Targeting FVIII expression to platelets does
not induce or elevate thrombosis risk. Platelets expressing FVIII are neither
hyper-activated nor hyper-responsive. SUMMARY: Background Targeting factor (F)
VIII expression to platelets is a promising gene therapy approach for hemophilia
A, and is successful even in the presence of inhibitors. It is well known that
platelets play important roles not only in hemostasis, but also in thrombosis and
inflammation. Objective To evaluate whether platelet-FVIII expression might
increase thrombotic risk and thereby compromise the safety of this approach.
Methods In this study, platelet-FVIII-expressing transgenic mice were examined
either in steady-state conditions or under prothrombotic conditions induced by
inflammation or the FV Leiden mutation. Native whole blood thrombin generation
assay, rotational thromboelastometry analysis and ferric chloride-induced vessel
injury were used to evaluate the hemostatic properties. Various parameters
associated with thrombosis risk, including D-dimer, thrombin-antithrombin
complexes, fibrinogen, tissue fibrin deposition, platelet activation status and
activatability, and platelet-leukocyte aggregates, were assessed. Results We
generated a new line of transgenic mice that expressed 30-fold higher levels of
platelet-expressed FVIII than are therapeutically required to restore hemostasis
in hemophilic mice. Under both steady-state conditions and prothrombotic
conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden
mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to
be thrombogenic. Furthermore, FVIII-expressing platelets were neither
hyperactivated nor hyperactivatable upon agonist activation. Conclusion We
conclude that, in mice, more than 30-fold higher levels of platelet-expressed
FVIII than are required for therapeutic efficacy in hemophilia A are not
associated with a thrombotic predilection.
PMID- 27496753
TI - Glycogen Storage Disease Because of a PRKAG2 Mutation Causing Severe
Biventricular Hypertrophy and High-Grade Atrio-Ventricular Block.
PMID- 27496754
TI - Comprehensive Hemodynamic Assessment in a Single Echocardiography Still Frame.
PMID- 27496752
TI - Role of interleukin-18 in the pathophysiology of allergic diseases.
AB - Interleukin (IL)-18 is an IL-1 family cytokine expressed by macrophages,
dendritic cells, epithelial cells, and keratinocytes and is implicated in various
aspects of both the innate and adaptive immune systems. IL-18 signals similar to
IL-1beta intracellularly to activate gene transcription. Since its discovery, IL
18 has been demonstrated to play a key role in pathogen defense from helminths
and some bacteria. Recently however, evidence has accumulated that IL-18
expression is increased in many presentations of allergic disease. A pathologic
role for IL-18 includes stimulating mast cell and basophil degranulation,
recruiting granulocytes to sites of inflammation, increasing cytotoxic activity
of natural killer (NK) and NK-T cells, inducing Immunoglobulin (Ig)E production
and isotype switching, and affecting a broad range of T cells to promote a type
II helper T cell (Th2) response. Evidence and importance of these effects are
presented, including novel results from our lab implicating IL-18 in the direct
expansion of mast cells, basophils, and other myeloid-lineage cells from bone
marrow precursors. The development of urticaria, asthma, dermatitis, rhinitis,
and eosinophilic disorders all have demonstrated correlations to increased IL-18
levels either in the tissue or systemically. IL-18 represents a novel site of
immune regulation in not only allergic conditions, but also autoimmune diseases
and other instances of aberrant immune functioning. Diagrammatic summarized
abstract for readers convinance is presented in Fig. 1.
PMID- 27496755
TI - Metabolism and functional effects of plant-derived omega-3 fatty acids in humans.
AB - Alpha-linolenic acid (ALA) is an essential fatty acid and the substrate for the
synthesis of longer-chain, more unsaturated omega-3 fatty acids, eicosapentaenoic
acid (EPA), docosapentaenoic acid and docosahexaenoic acid (DHA). EPA and DHA are
associated with human health benefits. The primary source of EPA and DHA is
seafood. There is a need for sustainable sources of biologically active omega-3
fatty acids. Certain plants contain high concentrations of ALA and stearidonic
acid (SDA). Here we review the literature on the metabolism of ALA and SDA in
humans, the impact of increased ALA and SDA consumption on concentrations of EPA
and DHA in blood and cell lipid pools, and the extent to which ALA and SDA might
have health benefits. Although it is generally considered that humans have
limited capacity for conversion of ALA to EPA and DHA, sex differences in
conversion to DHA have been identified. If conversion of ALA to EPA and DHA is
limited, then ALA may have a smaller health benefit than EPA and DHA. SDA is more
readily converted to EPA and appears to offer better potential for health
improvement than ALA. However, conversion of both ALA and SDA to DHA is limited
in most humans.
PMID- 27496756
TI - Editorial Comment.
PMID- 27496758
TI - Chitosan conjugation enables intracellular bacteria susceptible to aminoglycoside
antibiotic.
AB - Most chronic infections are difficult to eradicate because bacteria capable of
surviving in host-infected cells may be protected from the killing actions of
antibiotics, leading to therapy failures and disease relapses. Here we
demonstrated that covalent-coupling chitosan to streptomycin significantly
improved intracellular bactericidal capacity towards multiple organisms within
phagocytic or nonphagocytic cells. Structure-activity relationship investigations
indicated that antibiotic contents, molecular size and positive charges of the
conjugate were the key to retain this intracellular bactericidal activity.
Mechanistic insight demonstrated the conjugate was capable to target and
eliminate endocytic or endosomal escaped bacteria through facilitating the direct
contact between the antibiotic and intracellular organism. In vivo acute
infection models indicated that compared to equal dose of the antibiotic,
chitosan-streptomycin (C-S) conjugate and especially the human serum album
binding chitosan-streptomycin conjugate (HCS) complex formed by human serum album
and C-S conjugate greatly decreased the bacteria burden in the spleen and liver
in both wild type and immuno-suppressive mice. Furthermore, the HCS complex
remarkably reduced mortality of infected TLR2 deficient mice, mimicking immune
compromised persons who were more susceptible to bacterial infections. These
findings might open up a new avenue to combat intracellular bacterial infection
by aminoglycosides antibiotics at a lower effective dose.
PMID- 27496757
TI - Estimating glycosaminoglycan-protein interaction affinity: water dominates the
specific antithrombin-heparin interaction.
AB - Glycosaminoglycan (GAG)-protein interactions modulate many important biological
processes. Structure-function studies on GAGs may reveal probes and drugs, but
their structural complexity and highly acidic nature confound such work.
Productivity will increase if we are able to identify tight-binding
oligosaccharides in silico. An extension of the CHARMM force field is presented
to enable modeling of polysaccharides containing sulfamate functionality, and is
used to develop a reliable alchemical free-energy perturbation protocol that
estimates changes in affinity for the prototypical heparin-antithrombin system to
within 2.3 kcal/mol using modest simulation times. Inclusion of water is crucial
during simulation as solvation energy was equal in magnitude to the sum of all
other thermodynamic factors. In summary, we have identified and optimized a
reliable method for estimation of GAG-protein binding affinity, and shown that
solvation is a crucial component in GAG-protein interactions.
PMID- 27496759
TI - Rational design of a thermostable glycoside hydrolase from family 3 introduces
beta-glycosynthase activity.
AB - The thermostable beta-glucosidase from Thermotoga neapolitana, TnBgl3B, is a
monomeric three-domain representative from glycoside hydrolase family 3. By using
chemical reactivation with exogenous nucleophiles in previous studies with
TnBg13B, the catalytic nucleophile (D242) and corresponding acid/base residue
(E458) were determined. Identifying these residues led to the attempt of
converting TnBgl3B into a beta-glucosynthase, where three nucleophilic variants
were created (TnBgl3B_D242G, TnBgl3B_D242A, TnBgl3B_D242S) and all of them failed
to exhibit glucosynthase activity. A deeper analysis of the TnBgl3B active site
led to the generation of three additional variants, each of which received a
single-point mutation. Two of these variants were altered at the -1 subsite
(Y210F, W243F) and the third received a substitution near the binding site's
aglycone region (N248R). Kinetic evaluation of these three variants revealed that
W243F substitution reduced hydrolytic turnover while maintaining KM This key
W243F mutation was then introduced into the original nucleophile variants and the
resulting double mutants were successfully converted into beta-glucosynthases
that were assayed using two separate biosynthetic methods. The first reaction
used an alpha-glucosyl fluoride donor with a 4-nitrophenyl-beta-d-glucopyranoside
(4NPGlc) acceptor, and the second used 4NPGlc as both the donor and acceptor in
the presence of the exogenous nucleophile formate. The primary specificity
observed was a beta-1,3-linked disaccharide product, while a secondary beta-1,4
linked disaccharide product was observed with increased incubation times.
Additional analysis revealed that substituting quercetin-3-glycoside for the
second reaction's acceptor molecule resulted in the successful production of
quercetin-3,4'-diglycosides with yields up to 40%.
PMID- 27496761
TI - Oligosaccharides from the 3-linked 2-sulfated alpha-L-fucan and alpha-L-galactan
show similar conformations but different dynamics.
AB - Here we have performed an nuclear magnetic resonance-based study on the ring and
chain conformations as well as dynamics of oligosaccharides generated by acid
hydrolysis on two structurally related glycans, a 3-linked 2-sulfated alpha-L
galactan and a 3-linked 2-sulfated alpha-L-fucan. Results derived from scalar
couplings have confirmed the 1C4 chair configuration to both alpha-L-fucose and
alpha-L-galactose, and a similar solution 3D structure for the oligosaccharide
chains of both sulfated glycans as seen on the basis of NOE patterns.
Measurements of spin-relaxation rates have suggested, however, a slight
difference dynamical property to these glycans. The fucose-based oligosaccharides
showed an enhanced dynamical property if compared to the galactose-based
oligosaccharides of same anomericity, sugar configuration, glycosidic bond and
sulfation type. This distinction solely on the dynamical aspect has been driven
therefore by the different sugar composition of the two studied sulfated glycans.
PMID- 27496760
TI - Cryptococcus neoformans UGT1 encodes a UDP-Galactose/UDP-GalNAc transporter.
AB - Cryptococcus neoformans, an opportunistic fungal pathogen, produces a glycan
capsule to evade the immune system during infection. This definitive virulence
factor is composed mainly of complex polysaccharides, which are made in the
secretory pathway by reactions that utilize activated nucleotide sugar
precursors. Although the pathways that synthesize these precursors are known, the
identity and the regulation of the nucleotide sugar transporters (NSTs)
responsible for importing them into luminal organelles remain elusive. The UDP
galactose transporter, Ugt1, was initially identified by homology to known UGTs
and glycan composition analysis of ugt1Delta mutants. However, sequence is an
unreliable predictor of NST substrate specificity, cells may express multiple
NSTs with overlapping specificities, and NSTs may transport multiple substrates.
Determining NST activity thus requires biochemical demonstration of function. We
showed that Ugt1 transports both UDP-galactose and UDP-N-acetylgalactosamine in
vitro. Deletion of UGT1 resulted in growth and mating defects along with altered
capsule and cellular morphology. The mutant was also phagocytosed more readily by
macrophages than wild-type cells and cleared more quickly in vivo and in vitro,
suggesting a mechanism for the lack of virulence observed in mouse models of
infection.
PMID- 27496762
TI - Saturation transfer difference nuclear magnetic resonance titrations reveal
complex multistep-binding of l-fucose to norovirus particles.
AB - Recently, combined nuclear magnetic resonance (NMR), native mass spectrometry
(MS) and X-ray crystallographic studies have demonstrated that binding of histo
blood group antigens (HBGAs) to norovirus capsid protein (P-dimers) is a
cooperative process involving four binding pockets. Here, we show that binding to
norovirus virus-like particles (VLPs) is even more complex. We performed
saturation transfer difference (STD) NMR titration experiments with two
representative genotypes of norovirus VLPs using l-fucose as a minimal HBGA.
Compared to titrations with P-dimers, the corresponding binding isotherms reflect
at least six distinct binding events.
PMID- 27496763
TI - Chemical Glycobiology.
PMID- 27496764
TI - The structural investigation of glycosaminoglycan binding to CXCL12 displays
distinct interaction sites.
AB - The stromal cell-derived factor 1alpha (CXCL12) belongs to the CXC chemokine
family and plays an important role in tissue regeneration and the recruitment of
stem cells. Here, a stable chemotactic gradient is essential that is formed by
the interaction of CXCL12 with the extracellular matrix. Binding properties of
CXCL12 to naturally occurring glycosaminoglycans (GAGs) as well as to the
artificial highly sulfated hyaluronic acid (HA) are investigated by using a
combination of NMR spectroscopy, molecular modeling and molecular dynamics
simulations. Our results demonstrate a preferred protein binding for the sulfated
GAGs heparin (HE) and highly sulfated HA. Furthermore, we could demonstrate that
the orientation of the sulfate is crucial for binding. All sulfated GAGs interact
with the CXCL12 GAG-binding motif (K24-H25-L26-K27-R41-K43-R47), where K27 and
R41 represent the anchor points. Furthermore, differences could be observed in
the second interaction interface of CXCL12: both HE and highly sulfated HA
interfere with the receptor-binding motif, while chondroitin sulfate binds
different amino acids in close proximity to this motif. CXCL12 does not interact
with HA, which was directly demonstrated by NMR spectroscopy and molecular
modeling and explained by the lack of sulfate groups of the HA molecule.
PMID- 27496766
TI - Effects of domain composition on catalytic activity of human UDP
glucose:glycoprotein glucosyltransferases.
AB - Uridine diphosphate (UDP)-glucose:glycoprotein glucosyltransferase (UGGT) 1 is a
soluble protein residing in the endoplasmic reticulum (ER) and partially in ER
Golgi intermediate compartment. Characteristically, it is able to recognize
incompletely folded proteins and re-glucosylate their high-mannose-type glycans.
By virtue of this, UGGT1 acts as a folding sensor in the glycoprotein quality
control system in the ER. On the other hand, human UGGT2 (HUGT2) has been
believed to be an inactive homolog of human UGGT1 (HUGT1), whereas our recent
study discovered its activity as UGGT. Although the activity of HUGT2 is
significantly lower than HUGT1, C-terminal catalytic region, accounting for
approximately 20% of the full-length enzyme, shares high amino acid sequence
identity (>85%). In this study, we aimed to clarify the contribution of the
noncatalytic domains by comparing activities of truncated forms of recombinant
HUGT1/HUGT2 and HUGT1/HUGT2 chimeras with full-length enzymes. Our results
obtained by using synthetic substrate indicate that the C-terminal catalytic
regions of HUGTs are functional as UGGT. While the activity of HUGT1, but not
that of HUGT2, was enhanced by the presence of N-terminal domains, activities of
catalytic domains are similar between two homologs.
PMID- 27496765
TI - LARGE2-dependent glycosylation confers laminin-binding ability on proteoglycans.
AB - Both LARGE1 (formerly LARGE) and its paralog LARGE2 are bifunctional
glycosyltransferases with xylosy- and glucuronyltransferase activities, and are
capable of synthesizing polymers composed of a repeating disaccharide [
3Xylalpha1,3GlcAbeta1-]. Post-translational modification of the O-mannosyl glycan
of alpha-dystroglycan (alpha-DG) with the polysaccharide is essential for it to
act as a receptor for ligands in the extracellular matrix (ECM), and both LARGE
paralogs contribute to the modification in vivo. LARGE1 and LARGE2 have different
tissue distribution profiles and enzymatic properties; however, the functional
difference of the homologs remains to be determined, and alpha-DG is the only
known substrate for the modification by LARGE1 or LARGE2. Here we show that
LARGE2 can modify proteoglycans (PGs) with the laminin-binding glycan. We found
that overexpression of LARGE2, but not LARGE1, mediates the functional
modification on the surface of DG-/-, Pomt1-/- and Fktn-/- embryonic stem cells.
We identified a heparan sulfate-PG glypican-4 as a substrate for the LARGE2
dependent modification by affinity purification and subsequent mass spectrometric
analysis. Furthermore, we showed that LARGE2 could modify several additional PGs
with the laminin-binding glycan, most likely within the glycosaminoglycan (GAG)
protein linkage region. Our results indicate that LARGE2 can modify PGs with the
GAG-like polysaccharide composed of xylose and glucuronic acid to confer laminin
binding. Thus, LARGE2 may play a differential role in stabilizing the basement
membrane and modifying its functions by augmenting the interactions between
laminin globular domain-containing ECM proteins and PGs.
PMID- 27496767
TI - Computational analysis of interactions in structurally available protein
glycosaminoglycan complexes.
AB - Glycosaminoglycans represent a class of linear anionic periodic polysaccharides,
which play a key role in a variety of biological processes in the extracellular
matrix via interactions with their protein targets. Computationally,
glycosaminoglycans are very challenging due to their high flexibility,
periodicity and electrostatics-driven nature of the interactions with their
protein counterparts. In this work, we carry out a detailed computational
characterization of the interactions in protein-glycosaminoglycan complexes from
the Protein Data Bank (PDB), which are split into two subsets accounting for
their intrinsic nature: non-enzymatic-protein-glycosaminoglycan and enzyme
glycosaminoglycan complexes. We apply molecular dynamics to analyze the
differences in these two subsets in terms of flexibility, retainment of the
native interactions in the simulations, free energy components of binding and
contributions of protein residue types to glycosaminoglycan binding. Furthermore,
we systematically demonstrate that protein electrostatic potential calculations,
previously found to be successful for glycosaminoglycan binding sites prediction
for individual systems, are in general very useful for proposing protein surface
regions as putative glycosaminoglycan binding sites, which can be further used
for local docking calculations with these particular polysaccharides. Finally,
the performance of six different docking programs (Autodock 3, Autodock Vina,
MOE, eHiTS, FlexX and Glide), some of which proved to perform well for particular
protein-glycosaminoglycan complexes in previous work, is evaluated on the
complete protein-glycosaminoglycan data set from the PDB. This work contributes
to widen our knowledge of protein-glycosaminoglycan molecular recognition and
could be useful to steer a choice of the strategies to be applied in theoretical
studies of these systems.
PMID- 27496768
TI - Development of N- and O-linked oligosaccharide engineered Saccharomyces
cerevisiae strain.
AB - Yeast cells have been engineered for the production of glycoproteins as
biopharmaceuticals with humanized N-linked oligosaccharides. The suppression of
yeast-specific O-mannosylation is important to reduce immune response and to
improve heterologous protein productivity in the production of
biopharmaceuticals. However, so far, there are few reports of the engineering of
both N-linked and O-linked oligosaccharides in yeast cells. In the present study,
we describe the generation of a Saccharomyces cerevisiae strain capable of
producing a glycoprotein with humanized Man5GlcNAc2 N-linked oligosaccharides, an
intermediate of mammalian hybrid- and complex-type oligosaccharides, while
suppressing O-mannosylation. First, a yeast strain that produces a glycoprotein
with Man5GlcNAc2 was isolated by introducing msdS encoding alpha-1,2-mannosidase
into a strain synthesizing Man8GlcNAc2 N-linked oligosaccharides. Next, to
suppress O-mannosylation, an O-mannosyltransferase-deficient strain was generated
by disrupting PMT1 and PMT2 Although the relative amount of O-linked
oligosaccharides in the disruptant was reduced to approximately 40% of that in
wild type cells, this strain exhibited growth defects and decreased protein
productivity. To overcome the growth defects, we applied a mutagenesis technique
that is based on the disparity theory of evolution. Finally, to improve protein
productivity of the growth-recovered strain, vacuolar proteases PEP4 and PRB1
were further disrupted. Thus, by combining genetic engineering and disparity
mutagenesis, we generated an Saccharomyces cerevisiae strain whose N- and O
linked oligosaccharide synthetic pathways were engineered to effectively produce
the heterologous protein.
PMID- 27496769
TI - Increase in cannabis use may indirectly affect the health status of a freshwater
species.
AB - Cannabis is the most used illicit drug worldwide and in some countries a new
regulatory policy makes it legal under some restrictions. This situation could
lead to a substantial increase in environmental levels of the cannabis active
principle (Delta-9-tetrahydrocannabinol [Delta-9-THC]) and its main metabolite,
11-nor-9-carboxy-Delta9 -tetrahydrocannabinol (THC-COOH). Although previous
studies have highlighted the toxicity of Delta-9-THC, the adverse effects of THC
COOH on aquatic organisms is completely unknown, even though such effects could
be more significant because the environmental concentrations of THC-COOH are
higher than those of the parent compound. The present study aimed to assess
oxidative and genetic damage to the zebra mussel (Dreissena polymorpha) because
of 14-d exposures to 3 THC-COOH concentrations, mimicking a current environmental
situation (100 ng/L), as well as exposure to 2 possible worst-case scenarios (500
ng/L and 1000 ng/L), because of the potential increase in THC-COOH in surface
waters. Variations in the activity of catalase (CAT), superoxide dismutase (SOD),
glutathione peroxidase (GPx), and glutathione S-transferase (GST) were measured,
as well as levels of lipid peroxidation and protein carbonyl content. Genetic
injuries were investigated by single-cell gel electrophoresis assay, DNA
diffusion assay, and the micronucleus test. A significant imbalance in
antioxidant defense enzymes was noted in response to the 3 tested concentrations,
whereas oxidative damage was noted only at the higher one. Moreover, an increase
in DNA fragmentation in zebra mussel hemocytes, but no fixed genetic damage, was
found. Although the results showed that THC-COOH toxicity was lower than that of
Delta-9-THC, the increase in cannabis use might increase its levels in
freshwaters, enhancing its hazard to bivalves and likely to the whole aquatic
community. Environ Toxicol Chem 2017;36:472-479. (c) 2016 SETAC.
PMID- 27496770
TI - High-dose rate brachytherapy as monotherapy in prostate cancer: A systematic
review of its safety and efficacy.
AB - CONTEXT: High-dose rate brachytherapy (HDR-BT) is an increasingly popular
treatment for patients with localised prostate cancer (PC). OBJECTIVE: To assess
the safety and efficacy of HDR-BT as monotherapy in PC. ACQUISITION OF EVIDENCE:
A systematic literature review was conducted through searches on MEDLINE
(PubMed), Cochrane Library, CDR, ClinicalTrials and EuroScan. We assessed safety
and efficacy indicators. SUMMARY OF THE EVIDENCE: We selected 2 reviews and 12
uncontrolled studies, included in these 2 reviews. In terms of efficacy, local
control in 6 studies was 97-100%. The biochemical progression-free survival
varied as follows: 85-100% for low risk and 79-92% for high risk. Survival free
of metastases was >95% at 8 years, except in one study where the survival rate
was 87% at 5 years. The overall survival was >=95% in 8 studies. In terms of
safety, most of the studies recorded acute and long-term genitourinary and
gastrointestinal complications, especially grade >=2. Only 3 studies found grade
4 complications. All studies, except for one without complications, observed
genitourinary complications that were more frequent and severe than the
gastrointestinal complications. Two studies assessed the quality of life and
showed an initial reduction in various domains and subsequent partial or total
recovery, except in the sexual domain. CONCLUSIONS: HDR-BT is effective as
monotherapy, especially in cases of low to intermediate risk. There is
insufficient information on high-risk patients. The short to medium-term toxicity
was acceptable. Further research needs to be funded to provide more information
on the long-term safety and efficacy of this treatment.
PMID- 27496771
TI - Adipocyte accumulation in corpus cavernosum: First clinical evidence and
pathophysiological implications in erectile dysfunction.
AB - OBJECTIVES: Animal models have shown that erectile dysfunction is associated with
adipocyte accumulation under tunica albuginea, which could be involved in venous
leakage and loss of penile rigidity. In the current sudy, we compared the
histology of the penile sub-albuginean region of drug-refractory erectile
dysfunction patients undergoing penile prosthesis implantation with potent
patients with Peyronie's disease undergoing curvature correction procedures.
MATERIALS AND METHODS: Seventeen refractory erectile dysfunction patients and
fourteen potent patients with Peyronie's disease were recruited. Sub-albuginean
tissue samples were taken in each surgery. An expert uropathologist analysed each
section. A bivariate analysis was performed. Multivariate logistic regression was
used to calculate adjusted odds ratios; P value<.05 was considered significant.
RESULTS: Eleven patients (11/17) in the case group presented cavernous fat cell
accumulation, while only one patient (1/14) in the control group presented this
finding (P<.05). Adjusted odds ratio for erectile dysfunction was 40.72; 95% CI
2.28-727.29 (P=.012). CONCLUSIONS: Different studies have shown that androgen
disruption could be involved in penile structural changes, leading to trabecular
smooth muscle apoptosis and trans or de-differentiation into adipocytes. This is
the first prospective study in humans to report an association between erectile
dysfunction and sub-albuginean adipocyte accumulation. Venous leakage secondary
to this phenomenon could be a factor in the pathophysiology of erectile
dysfunction, especially in patients that do not respond to medical therapy.
PMID- 27496772
TI - Is the adjustable TVA mesh effective for the long-term treatment of female stress
incontinence?
AB - OBJECTIVES: To assess the long-term safety and efficacy of the adjustable TVA
mesh in treating stress urinary incontinence. MATERIAL AND METHODS:
Pseudoexperimental study, before and after, conducted in a university urology
department. Eighty-two patients were invited to participate from January 2002 to
March 2005. Thirty-two patients agreed to participate and were implanted an
adjustable TVA mesh. The preoperative study included a medical history review,
physical examination with full bladder, flowmetry, residue study, complete
urodynamic study and the self-administered questionnaires I-QoL and ICIQ-SF. In
the postoperative assessment, the PGI-I questionnaire was added, but a complete
urodynamic study was not performed. RESULTS: Twenty-nine (90.6%) and 28 (87.5%)
patients were continent in the stress test at 1 and 10 years, respectively.
Twenty (62.5%) and 16 (50%) patients had no urine escape at 1 and 10 years,
respectively. Twenty-eight (87.5%) and 25 (78%) patients were satisfied 1 and 10
years after the surgery, respectively. Twenty-eight (87.5%) and 21 (62.5%)
patients had a good quality of life at 1 year and at 10 years, respectively.
There were no significant complications at the end of the study period.
CONCLUSIONS: Treatment of stress urinary incontinence with the TVA mesh presented
a high degree of objective healing and satisfaction at 10 years, with no severe
adverse effects. The study showed that satisfaction does not always mean total
continence but rather it reflects the improvement of symptoms and consequent
quality of life.
PMID- 27496773
TI - Carbon Catabolite Repression and Impranil Polyurethane Degradation in Pseudomonas
protegens Strain Pf-5.
AB - : Polyester polyurethane (PU) coatings are widely used to help protect underlying
structural surfaces but are susceptible to biological degradation. PUs are
susceptible to degradation by Pseudomonas species, due in part to the degradative
activity of secreted hydrolytic enzymes. Microorganisms often respond to
environmental cues by secreting enzymes or secondary metabolites to benefit their
survival. This study investigated the impact of exposing several Pseudomonas
strains to select carbon sources on the degradation of the colloidal polyester
polyurethane Impranil DLN (Impranil). The prototypic Pseudomonas protegens strain
Pf-5 exhibited Impranil-degrading activities when grown in sodium citrate but not
in glucose-containing medium. Glucose also inhibited the induction of Impranil
degrading activity by citrate-fed Pf-5 in a dose-dependent manner. Biochemical
and mutational analyses identified two extracellular lipases present in the Pf-5
culture supernatant (PueA and PueB) that were involved in degradation of
Impranil. Deletion of the pueA gene reduced Impranil-clearing activities, while
pueB deletion exhibited little effect. Removal of both genes was necessary to
stop degradation of the polyurethane. Bioinformatic analysis showed that putative
Cbr/Hfq/Crc-mediated regulatory elements were present in the intergenic sequences
upstream of both pueA and pueB genes. Our results confirmed that both PueA and
PueB extracellular enzymes act in concert to degrade Impranil. Furthermore, our
data showed that carbon sources in the growth medium directly affected the levels
of Impranil-degrading activity but that carbon source effects varied among
Pseudomonas strains. This study uncovered an intricate and complicated regulation
of P. protegens PU degradation activity controlled by carbon catabolite
repression. IMPORTANCE: Polyurethane (PU) coatings are commonly used to protect
metals from corrosion. Microbiologically induced PU degradation might pose a
substantial problem for the integrity of these coatings. Microorganisms from
diverse genera, including pseudomonads, possess the ability to degrade PUs via
various means. This work identified two extracellular lipases, PueA and PueB,
secreted by P. protegens strain Pf-5, to be responsible for the degradation of a
colloidal polyester PU, Impranil. This study also revealed that the expression of
the degradative activity by strain Pf-5 is controlled by glucose carbon
catabolite repression. Furthermore, this study showed that the Impranil-degrading
activity of many other Pseudomonas strains could be influenced by different
carbon sources. This work shed light on the carbon source regulation of PU
degradation activity among pseudomonads and identified the polyurethane lipases
in P. protegens.
PMID- 27496774
TI - Multivalent Chromosomal Expression of the Clostridium botulinum Serotype A
Neurotoxin Heavy-Chain Antigen and the Bacillus anthracis Protective Antigen in
Lactobacillus acidophilus.
AB - : Clostridium botulinum and Bacillus anthracis produce potent toxins that cause
severe disease in humans. New and improved vaccines are needed for both of these
pathogens. For mucosal vaccine delivery using lactic acid bacteria, chromosomal
expression of antigens is preferred over plasmid-based expression systems, as
chromosomal expression circumvents plasmid instability and the need for
antibiotic pressure. In this study, we constructed three strains of Lactobacillus
acidophilus NCFM expressing from the chromosome (i) the nontoxic host receptor
binding domain of the heavy chain of Clostridium botulinum serotype A neurotoxin
(BoNT/A-Hc), (ii) the anthrax protective antigen (PA), and (iii) both the BoNT/A
Hc and the PA. The BoNT/A-Hc vaccine cassette was engineered to contain the
signal peptide from the S-layer protein A from L. acidophilus and a dendritic
cell-targeting peptide. A chromosomal region downstream of lba0889 carrying a
highly expressed enolase gene was selected for insertion of the vaccine
cassettes. Western blot analysis confirmed the heterologous expression of the two
antigens from plasmid and chromosome locations. Stability assays demonstrated
loss of the vaccine cassettes from expression plasmids without antibiotic
maintenance. RNA sequencing showed high expression of each antigen and that
insertion of the vaccine cassettes had little to no effect on the transcription
of other genes in the chromosome. This study demonstrated that chromosomal
integrative recombinant strains are promising vaccine delivery vehicles when
targeted into high-expression chromosomal regions. Levels of expression match
high-copy-number plasmids and eliminate the requirement for antibiotic selective
maintenance of recombinant plasmids. IMPORTANCE: Clostridium botulinum and
Bacillus anthracis produce potent neurotoxins that pose a biochemical warfare
concern; therefore, effective vaccines against these bacteria are required.
Chromosomal expression of antigens is preferred over plasmid-based expression
systems since expressing antigens from a chromosomal location confers an
advantage to the vaccine strains by eliminating the antibiotic maintenance
required for plasmids and negates issues with plasmid instability that would
result in loss of the antigen. Lactic acid bacteria, including Lactobacillus
acidophilus, have shown potential for mucosal vaccine delivery, as L. acidophilus
is bile and acid tolerant, allowing transit through the gastrointestinal tract
where cells interact with host epithelial and immune cells, including dendritic
cells. In this study, we successfully expressed C. botulinum and B. anthracis
antigens in the probiotic L. acidophilus strain NCFM. Both antigens were highly
expressed individually or in tandem from the chromosome of L. acidophilus.
PMID- 27496775
TI - Extending CRISPR-Cas9 Technology from Genome Editing to Transcriptional
Engineering in the Genus Clostridium.
AB - : The discovery and exploitation of the prokaryotic adaptive immunity system
based on clustered regularly interspaced short palindromic repeats (CRISPRs) and
CRISPR-associated (Cas) proteins have revolutionized genetic engineering. CRISPR
Cas tools have enabled extensive genome editing as well as efficient modulation
of the transcriptional program in a multitude of organisms. Progress in the
development of genetic engineering tools for the genus Clostridium has lagged
behind that of many other prokaryotes, presenting the CRISPR-Cas technology an
opportunity to resolve a long-existing issue. Here, we applied the Streptococcus
pyogenes type II CRISPR-Cas9 (SpCRISPR-Cas9) system for genome editing in
Clostridium acetobutylicum DSM792. We further explored the utility of the
SpCRISPR-Cas9 machinery for gene-specific transcriptional repression. For proof
of-concept demonstration, a plasmid-encoded fluorescent protein gene was used for
transcriptional repression in C. acetobutylicum Subsequently, we targeted the
carbon catabolite repression (CCR) system of C. acetobutylicum through
transcriptional repression of the hprK gene encoding HPr kinase/phosphorylase,
leading to the coutilization of glucose and xylose, which are two abundant carbon
sources from lignocellulosic feedstocks. Similar approaches based on SpCRISPR
Cas9 for genome editing and transcriptional repression were also demonstrated in
Clostridium pasteurianum ATCC 6013. As such, this work lays a foundation for the
derivation of clostridial strains for industrial purposes. IMPORTANCE: After
recognizing the industrial potential of Clostridium for decades, methods for the
genetic manipulation of these anaerobic bacteria are still underdeveloped. This
study reports the implementation of CRISPR-Cas technology for genome editing and
transcriptional regulation in Clostridium acetobutylicum, which is arguably the
most common industrial clostridial strain. The developed genetic tools enable
simpler, more reliable, and more extensive derivation of C. acetobutylicum mutant
strains for industrial purposes. Similar approaches were also demonstrated in
Clostridium pasteurianum, another clostridial strain that is capable of utilizing
glycerol as the carbon source for butanol fermentation, and therefore can be
arguably applied in other clostridial strains.
PMID- 27496776
TI - Epidemiological Investigation of Legionella pneumophila Serogroup 2 to 14
Isolates from Water Samples by Amplified Fragment Length Polymorphism and
Sequence-Based Typing and Detection of Virulence Traits.
AB - : The aim of this study is to explore the dispersion, clonality, and virulence of
Legionella pneumophila serogroups 2 to 14 in the Greek environment. Eighty L.
pneumophila serogroup 2 to 14 strains isolated from water distribution systems of
hotels, hospitals, athletic venues, and ferries in Greece were tested by
monoclonal antibodies (MAbs) for serogroup discrimination and molecularly by
amplified fragment length polymorphism (AFLP) for genetic diversity. Fifty-six of
80 strains were also typed by the sequence-based typing (SBT) method. Alphall
strains were further analyzed for detection of two pathogenicity loci: Legionella
vir homologue (lvh) and repeats in structural toxin (rtxA). Thirty-seven strains
(46.2%) belonged to serogroup 6, 26 strains (32.5%) to serogroup 3, and 7 (8.8%)
to other serogroups (4, 5, 8, and 10). Ten strains (12.5%) were nontypeable (NT)
into the known serogroups. Thirty-nine different AFLP types were found among the
80 L. pneumophila serogroup 2 to 14 strains, and 24 different SBT types were
found among the 56 strains tested. Among the 80 strains, the lvh locus was
present in 75 (93.8%), the rtxA locus was found in 76 (95%), and both loci were
found in 73 (91.3%) strains. This study showed that there is genetic variability
of L. pneumophila serogroups 2 to 14 in the Greek environment as well as a high
percentage of the pathogenicity loci. Iotantroducing an effective diagnostic test
for L. pneumophila serogroups 2 to 14 in urine and promoting the examination of
respiratory specimens from patients hospitalized for pneumonia in Greek hospitals
are essential. IMPORTANCE: In this study, the dispersion, clonality, and
virulence of environmental isolates of Legionella pneumophila serogroups 2 to 14
(Lp2-14) in Greece were investigated. Genetic variability of Lp2-14 in the Greek
environment was identified together with the presence of the pathogenicity loci
in a high percentage of the isolates. Despite the high prevalence of Lp2-14 in
the Greek environment, no clinical cases were reported, which may be due to
underdiagnosis of the disease. Almost all the legionellosis cases are diagnosed
in Greece by using the urine antigen test, which is specific for Lp1. There is an
urgent need to improve the clinical diagnosis of legionellosis by introducing an
effective diagnostic test for Lp2-14 in urine and by promoting the PCR
examination of respiratory specimens from patients with compatible clinical
symptoms.
PMID- 27496777
TI - Evidence for the Existence of Autotrophic Nitrate-Reducing Fe(II)-Oxidizing
Bacteria in Marine Coastal Sediment.
AB - : Nitrate-reducing Fe(II)-oxidizing microorganisms were described for the first
time ca. 20 years ago. Most pure cultures of nitrate-reducing Fe(II) oxidizers
can oxidize Fe(II) only under mixotrophic conditions, i.e., when an organic
cosubstrate is provided. A small number of nitrate-reducing Fe(II)-oxidizing
cultures have been proposed to grow autotrophically, but unambiguous evidence for
autotrophy has not always been provided. Thus, it is still unclear whether or to
what extent Fe(II) oxidation coupled to nitrate reduction is an enzymatically
catalyzed and energy-yielding autotrophic process or whether Fe(II) is
abiotically oxidized by nitrite from heterotrophic nitrate reduction. The aim of
the present study was to find evidence for the existence of autotrophic nitrate
reducing Fe(II) oxidizers in coastal marine sediments. Microcosm incubations
showed that with increasing incubation times, the stoichiometric ratio of reduced
nitrate/oxidized Fe(II) [NO3-reduced/Fe(II)oxidized] decreased, indicating a
decreasing contribution of heterotrophic denitrification and/or an increasing
contribution of autotrophic nitrate-reducing Fe(II) oxidation over time. After
incubations of sediment slurries for >10 weeks, nitrate-reducing activity ceased,
although nitrate was still present. This suggests that heterotrophic nitrate
reduction had ceased due to the depletion of readily available organic carbon.
However, after the addition of Fe(II) to these batch incubation mixtures, the
nitrate-reducing activity resumed, and Fe(II) was oxidized, indicating the
activity of autotrophic nitrate-reducing Fe(II) oxidizers. The concurrent
reduction of 14C-labeled bicarbonate concentrations unambiguously proved that
autotrophic C fixation occurred during Fe(II) oxidation and nitrate reduction.
Our results clearly demonstrated that autotrophic nitrate-reducing Fe(II)
oxidizing bacteria were present in the investigated coastal marine sediments.
IMPORTANCE: Twenty years after the discovery of nitrate-reducing Fe(II)
oxidizers, it is still controversially discussed whether autotrophic nitrate
reducing Fe(II)-oxidizing microorganisms exist and to what extent Fe(II)
oxidation in this reduction/oxidation process is enzymatically catalyzed or which
role abiotic side reactions of Fe(II) with reactive N species play. Most pure
cultures of nitrate-reducing Fe(II) oxidizers are mixotrophic; i.e., they need an
organic cosubstrate to maintain their activity over several cultural transfers.
For the few existing autotrophic isolates and enrichment cultures, either the
mechanism of nitrate-reducing Fe(II) oxidation is not known or evidence for their
autotrophic lifestyle is controversial. In the present study, we provide evidence
for the existence of autotrophic nitrate-reducing Fe(II) oxidizers in coastal
marine sediments. The evidence is based on stoichiometries of nitrate reduction
and Fe(II) oxidation determined in microcosm incubations and the incorporation of
carbon from CO2 under conditions that favor the activity of nitrate-reducing
Fe(II) oxidizers.
PMID- 27496778
TI - Community-Based Culturally Preferred Physical Activity Intervention Targeting
Populations at High Risk for Type 2 Diabetes: Results and Implications.
AB - OBJECTIVES: In Canada, an ageing population, obesity rates and high risk among
certain ethnocultural populations are driving diabetes prevalence. Given the
burden associated with type 2 diabetes and its link to modifiable risk factors,
this study aimed to implement culturally preferred physical activities at the
community level, targeting individuals at high risk for type 2 diabetes. Glycated
hemoglobin (A1C) levels were used to detect potential improvements in glycemic
control. METHODS: Participants were screened for diabetes risk using a
questionnaire and capillary point-of-care A1C blood testing. Participants were
offered community-based physical activity classes 2 to 3 times per week for 6
months. A subset of participants (n=84) provided additional measurements.
RESULTS: In total, 718 subjects were reached during recruitment. Substantial
participant dropout took place, and 487 participants were exposed to the
intervention. Among those who participated in the physical activity and provided
follow up, mean A1C levels were reduced by 0.17 (p=0.002) after 3 months (n=84)
and by 0.06 (p=0.35; n=49) after 6 months. The homeostatic model assessment (HOMA
beta) showed a significant improvement of 23.6% after 3 months (n=20; p=0.03) and
45.2% after 6 months (n=12; p=0.02). Resting systolic blood pressure and
diastolic blood pressure plus combined hand-grip strength improved after 6 months
(n=12). CONCLUSIONS: Implementation of this community-based, culturally preferred
physical activity program presented several challenges and was associated with
significant participant dropout. After considering participant dropout, the
relatively small group who participated and provided follow-up measures showed
improvements various physiologic measures. Despite efforts to enhance
accessibility, it appears that several barriers to physical activity
participation remain and need to be explored to enhance the success of future
programs.
PMID- 27496780
TI - CNR 3/16, Societies' Communications.
PMID- 27496779
TI - Chronic Osteomyelitis and Atrial Fibrillation: Revisiting the Link Between
Inflammation Burden and Arrhythmia.
PMID- 27496781
TI - Reply to Lagana et al.'s comment on "Risk of developing major depression and
anxiety disorders among women with endometriosis: A longitudinal follow-up
study".
PMID- 27496782
TI - Prevalence of food allergy in infants and pre-schoolers in Brazil.
AB - BACKGROUND: Food allergy is an increasing problem in public health, especially in
childhood. Its incidence has increased in the last decade. Despite this,
estimates of the actual incidence and prevalence are uncertain. The aim of this
study was to estimate the prevalence of food allergy in infants and pre
schoolers. METHODS: The parents of 3897 children completed questionnaires on the
occurrence of any reaction to food. Children with parentally reported reactions
were selected for further examination including a clinical interview, physical
examination, allergic tests, and if necessary, oral food challenge to conclude
the diagnosis of FA. RESULTS: The estimated prevalence of allergy in children
aged 4-59 months was 0.61%, being, 1.9% in infants and 0.4% in pre-schoolers.
Among the 604 patients physicians evaluated with parent-reported FA, 24 (4%) had
a confirmed diagnosis of food allergy, and 580 (96%) were excluded in the
remaining. Of these, approximately half (51/52.6%) of 97 infants and (128/48%) of
487 pre-schoolers already performed the diet exclusion suspected food for a
period of time. CONCLUSION: This study shows that high overall prevalence of
parental belief of current food allergy however the same was not observed in the
in physician-diagnosed food allergy. The prevalence of food allergy was lower
than that observed in the literature. This study alerts health professionals to
the risk entailed by overestimation of cases of food allergy and unnecessary
dietary exclusion, which may result in impairment in growth and development of
children, especially in their first years of life.
PMID- 27496783
TI - Impact of rhinitis on lung function in children and adolescents without asthma.
AB - BACKGROUND: Subclinical spirometric abnormalities may be detected in patients
with rhinitis without asthma, proportional to the severity established by ARIA
(Allergic Rhinitis and Its Impact on Asthma) guidelines. New criteria of rhinitis
classification were recently validated according to the ARIA modified (m-ARIA),
which allow the discrimination between moderate to severe grades. The impact of
rhinitis on lung function according to frequency and severity is unknown.
OBJECTIVES: To investigate subclinical spirometric impairment in children and
adolescents with allergic and non-allergic rhinitis without overt symptoms of
asthma, according to the frequency and severity criteria of rhinitis classified
by m-ARIA. METHODS: An observational cross-sectional study, including children
and adolescents aged 5-18 years with allergic and non-allergic rhinitis without
asthma. We analysed the functional abnormalities and bronchodilator response with
spirometry in relation to the grade of rhinitis established by m-ARIA using an
adjusted logistic model. A value of p<0.05 was considered statistically
significant. RESULTS: We studied 189 patients; 22.2% showed spirometric
abnormalities. Patients with persistent rhinitis had greater impairment of lung
function compared to intermittent grade (p=0.026). Lung functional impairment was
more frequent in severe and moderate rhinitis than mild grade (p=0.005) and was
independent of the atopic status to both frequency (p=0.157) and severity
(p=0.538). There was no difference in bronchodilator reversibility between groups
(p>0.05). CONCLUSIONS: Impaired lung function was associated with persistence and
severity of rhinitis and there was no significant difference between patients
with moderate and severe rhinitis. The spirometric abnormality was demonstrated
in patients with allergic and non-allergic rhinitis.
PMID- 27496784
TI - Corneal Astigmatism and Aberrations After Combined Femtosecond-Assisted
Phacoemulsification and Arcuate Keratotomy: Two-Year Results.
AB - PURPOSE: To investigate the stability of corneal astigmatism and higher-order
aberrations after combined femtosecond-assisted phacoemulsification and arcuate
keratotomy. DESIGN: Retrospective, interventional case series. METHODS: Surgery
was performed using a VICTUS (Bausch & Lomb Inc, Dornach, Germany) platform. A
single, 450-MUm deep, arcuate keratotomy was paired at the 8-mm zone with the
main phacoemulsification incision in the opposite meridian. The keratotomy
incisions were not opened. Corneal astigmatism and higher-order aberration
measurements obtained preoperatively and at 2 months and 2 years postoperatively
were analyzed. RESULTS: Fifty eyes of 50 patients (mean age 66.2 +/- 10.5 years)
were included. The mean preoperative corneal astigmatism was 1.35 +/- 0.48
diopters (D). This was reduced to 0.67 +/- 0.54 D at 2 months and 0.74 +/- 0.53 D
at 2 years postoperatively (P < .001). There was no statistically significant
difference between postoperative corneal astigmatism over 2 years (P = .392).
Both magnitude of error and absolute angle of error were comparable between the 2
postoperative time points (P > .283). At postoperative 2 months and 2 years, 72%
and 70% of eyes were within 15 degrees of preoperative meridian of astigmatism,
respectively. All wavefront measurements increased significantly at 2 months and
2 years (P < .007), except spherical aberration (P > .150). There was no
significant difference in higher-order aberrations between 2 months and 2 years
postoperatively (P > .486). CONCLUSIONS: Our study showed the stability of
femtosecond-assisted arcuate keratotomy. Further studies using other platforms
and nomograms are needed to corroborate the findings of this study.
PMID- 27496785
TI - Choriocapillaris Flow Features Follow a Power Law Distribution: Implications for
Characterization and Mechanisms of Disease Progression.
AB - PURPOSE: To investigate flow characteristics of the choriocapillaris using
optical coherence tomography angiography. DESIGN: Retrospective observational
case series. METHODS: Visualization of flow in individual choriocapillary vessels
is below the current resolution limit of optical coherence tomography angiography
instruments, but areas of absent flow signal, called flow voids, are resolvable.
The central macula was imaged with the Optovue RTVue XR Avanti using a 10-MUm
slab thickness in 104 eyes of 80 patients who ranged in age from 24 to 99 years
of age. Automatic local thresholding of the resultant raw data with the
Phansalkar method was analyzed with generalized estimating equations. RESULTS:
The distribution of flow voids vs size of the voids was highly skewed. The data
showed a linear log-log plot and goodness-of-fit methods showed the data followed
a power law distribution over the relevant range. A slope intercept relationship
was also evaluated for the log transform and significant predictors for variables
included age, hypertension, pseudodrusen, and the presence of late age-related
macular degeneration (AMD) in the fellow eye. CONCLUSIONS: The pattern of flow
voids forms a scale invariant pattern in the choriocapillaris starting at a size
much smaller than a choroidal lobule. Age and hypertension affect the
choriocapillaris, a flat layer of capillaries that may serve as an observable
surrogate for the neural or systemic microvasculature. Significant alterations
detectable in the flow pattern in eyes with pseudodrusen and in eyes with late
AMD in the fellow eye offer diagnostic possibilities and impact theories of
disease pathogenesis.
PMID- 27496786
TI - Assessing the temporal aspects of attention and its correlates in aging and
chronic stroke patients.
AB - Temporal dynamics of attention have been in the spotlight of research since the
earliest days of cognitive psychology. Typically, researchers describe two
different aspects of the temporal fluctuations of attention: one is in intervals
of milliseconds (phasic alertness), and the other over minutes or even hours
(tonic alertness or sustained attention). In order to evaluate individual
capacities for sustained attention and phasic alertness, most studies rely on
variations of the Continuous Performance Task (CPT). Indices of sustained
attention and phasic alertness are typically based on reaction times to targets;
phasic alertness is related to the change in reaction times following a cue, and
sustained attention is related to variability of reaction times during the task.
In the following study, we attempted to establish a new approach for studying
sustained attention and phasic alertness, not reliant solely on reaction time
measures. We developed a new variation of the CPT with conjunctive feature
targets and forward and backward masking to induce a higher variability in
accuracy. This allowed us to assess an individual's ability to maintain the same
level of sensitivity to targets (d-prime) across a ten minute period on the task
as an index for sustained attention. We also assessed reaction times as a
function of previous trial type, and suggest previous trial RT benefit might be a
marker for an individual's phasic alertness. We demonstrated the use of this task
with healthy aging controls and stroke survivors. As a demonstration of external
validity of the novel paradigm, we present a correlation between how individual
performance drops over time and individual reports of distractibility in everyday
life on the Cognitive Failures Questionnaire. In addition, we found significant
differences between the patient and control groups in our proposed marker of
phasic alertness. We discuss the implications of our study for current assessment
tools, as well as general differences in phasic alertness between clinical and
neurologically unimpaired groups.
PMID- 27496787
TI - Explicit and implicit approach vs. avoidance tendencies towards high vs. low
calorie food cues in patients with anorexia nervosa and healthy controls.
AB - Patients with anorexia nervosa (AN) have a strong ability to limit food intake.
Thus, dysfunctional approach vs. avoidance behaviors towards food are evident in
AN. We applied an approach-avoidance task (AAT), in which n = 41 AN patients and
n = 42 controls either approached ("pull") or avoided ("push") high (HC) vs. low
calorie (LC) food pictures based solely on the presented picture format
(landscape vs. portrait). We tested the hypothesis that -in opposition to
controls displaying an approach bias towards HC food cues- AN patients would show
an avoidance bias (measured as different response times) towards HC food.
Explicit ratings of food cues were also performed. We found a significant
interaction "group" x "direction" (p = 0.03). rm-ANOVAs performed for each of the
two groups separately showed a main effect for "direction" of motion in controls
(p = 0.02), but not in AN patients (p = 0.40). The two groups did not differ in
their reaction times (RTs) with regard to "push" (p = 0.27). However, RTs with
regard to "pull" were significantly different between the groups (p = 0.04).
Controls show a clear approach bias, expressed by significantly faster RTs for
"pull" compared to "push", independent of "calorie" content of the food stimuli.
This approach bias is absent in the group of AN patients. This is indicative of a
global loss of incentive value of food in AN. Implicit trainings as add-on to
psychotherapy in AN patients are asked for.
PMID- 27496788
TI - Effects on satiation, satiety and food intake of wholegrain and refined grain
pasta.
AB - Wholegrains have received much attention in recent years due to their role in
prevention of obesity and its comorbidities. Many studies about energy regulation
are focused on the effect between meals (satiety), but the effect within meal
(satiation) for wholegrain foods has not been extensively studied. The objective
was to investigate the effect of WG pasta (WGP) compared to refined grain pasta
(RGP), on ad libitum energy intake (EI) within and at the subsequent meal as well
as appetite. Two different ad libitum lunch meals (study A) and two different iso
caloric lunch meals (study B) were administered in sixteen overweight/obese
subjects in a crossover design. The test meals consisted of RGP and WGP served
with tomato sauce. Study A: the ad libitum lunch meal was consumed then EI
registered. Study B: the iso-caloric lunch meal was served, then subjective
appetite sensation and breath hydrogen excretion were assessed for 240 min
followed by an ad libitum meal where EI was calculated. Overall, WGP did not
significantly differ in the effect on ad libitum EI within meal (p = 0.23) in
study A. In study B, WGP resulted in an increased sensation of satiety (p <
0.001) and lower ratings of hunger (p < 0.001) without increased in breath
hydrogen excretion (p = 0.11). Again, no overall effect on EI at the subsequent
meal was seen (p = 0.12). In conclusion, WGP increased satiety, diminished hunger
without modifying energy intake at the subsequent meals.
PMID- 27496790
TI - Annual meeting of Scottish Urology Society, 2015: Date: 26-27 February 2015,
Ayrshire.
PMID- 27496789
TI - Death Certification: 800 years of practice; time to modernise teaching?
AB - A short, personal perspective on the state of death certification teaching in the
UK from two foundation doctors, with a focus on the importance of certifying
death and the potential educational methods available to improve teaching on the
topic.
PMID- 27496791
TI - Association of serum chemerin concentrations with the presence of atrial
fibrillation.
AB - Objective Chemerin, a newly discovered adipokine, is correlated with
hypertension, diabetes and coronary heart disease. The aim of this study is to
investigate the association of serum chemerin concentrations with the presence of
atrial fibrillation. Methods Serum chemerin concentrations were determined in 256
patients with atrial fibrillation and 146 healthy subjects. Atrial fibrillation
patients were then divided into paroxysmal, persistent and permanent atrial
fibrillation. Results Serum chemerin concentrations were significantly higher in
atrial fibrillation patients compared with healthy controls. In subgroup studies,
patients with permanent atrial fibrillation had higher serum chemerin
concentrations than those with persistent and paroxysmal atrial fibrillation.
Furthermore, significant higher serum chemerin concentrations were observed in
persistent atrial fibrillation patients compared with paroxysmal atrial
fibrillation subjects. Serum chemerin concentrations were associated with the
presence of atrial fibrillation after logistic regression analysis. Pearson
correlation analysis revealed a positive relation of serum chemerin
concentrations with body mass index, systolic blood pressure, diastolic blood
pressure, triglycerides, low-density lipoprotein cholesterol, blood urea
nitrogen, creatinine, C-reactive protein and left atrial diameter. Conclusion
Serum chemerin concentrations are associated with the presence of atrial
fibrillation and atrial remodelling.
PMID- 27496792
TI - Haemoglobin variants may cause significant differences in haemoglobin A1c as
measured by high-performance liquid chromatography and enzymatic methods in
diabetic patients: a cross-sectional study.
AB - Background We aimed to determine whether the discrepancy between haemoglobin A1c
values determined by high-performance liquid chromatography and enzymatic
haemoglobin A1c measurements in diabetic patients was clinically relevant.
Methods We randomly recruited 1421 outpatients undergoing diabetic treatment and
follow-up who underwent at least three haemoglobin A1c measurements between April
2014 and March 2015 at our clinic. In 6369 samples, haemoglobin A1c was
simultaneously measured by HA-8160 and MetaboLead (enzymatic assay), and the
values were compared. Results haemoglobin A1c measurements by high-performance
liquid chromatography and enzymatic assay were strongly correlated (correlation
coefficient: 0.9828, linear approximation curve y = 0.9986x - 0.2507). Mean
haemoglobin A1c (6.8 +/- 1.0%) measured by high-performance liquid chromatography
was significantly higher than that measured by enzymatic assay (6.5 +/- 1.0%, P <
0.0001). During the sample processing, four (0.3%) subjects presented
consistently lower haemoglobin A1c values (<0.7%) by high-performance liquid
chromatography than those from enzymatic assay. Of these, three had Hb Toranomon
[beta112 (G14) Cys->Trp]. The fourth had Hb Ube-2 [alpha68 (E17) Asn->Asp]. One
other subject presented consistently higher haemoglobin A1c values (>1%) by high
performance liquid chromatography than those from enzymatic assay and was
diagnosed with a -77 (T > C) mutation in the delta-globin gene. These unrelated
asymptomatic subjects had normal erythrocyte profiles, without anaemia.
Conclusions We showed that haemoglobin A1c values measured by high-performance
liquid chromatography were significantly higher than those measured by enzymatic
assay in diabetic subjects. However, when an oversized deviation (>0.7%) between
glycaemic control status and haemoglobin A1c is apparent, clinicians should check
the methods used to measure haemoglobin A1c and consider the possible presence of
a haemoglobin variant.
PMID- 27496793
TI - Annexin A2 and its downstream IL-6 and HB-EGF as secretory biomarkers in the
differential diagnosis of Her-2 negative breast cancer.
AB - Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF
shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle
has a major role in cancer cell proliferation, migration and metastasis. The
objective of the study is to demonstrate annexinA2-mediated autocrine regulation
via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods
Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample
of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16).
Simultaneously, tissue expression was analysed by immunohistochemistry. The
membrane deposition of these secretory ligands and their autocrine regulation was
demonstrated using triple-negative breast cancer cell line model. Results
Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6
expression is seen in both Her-2 negative and positive breast cancer cells. RNA
interference studies and upregulation of annexinA2 proved that annexinA2 is the
upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted
in Her-2 negative breast cancer (359.28 +/- 63.73 ng/mL) compared with normal
(286.10 +/- 70.04 ng/mL, P < 0.01) and Her-2 positive cases (217.75 +/- 60.59
ng/mL, P < 0.0001). In Her-2 negative cases, the HB-EGF concentrations (179.16 +/
118.81 pg/mL) were highly significant compared with normal (14.92 +/- 17.33
pg/mL, P < 0.001). IL-6 concentrations were increased significantly in both the
breast cancer phenotypes as compared with normal ( P < 0.001). Conclusion The
specific expression pattern of annexinA2 and HB-EGF in triple-negative breast
cancer tissues, increased secretion compared with normal cells, and their major
role in the regulation of EGFR downstream signalling makes these molecules as a
potential tissue and serum biomarker and an excellent therapeutic target in Her-2
negative breast cancer.
PMID- 27496794
TI - Post-standardization of routine creatinine assays: are they suitable for clinical
applications.
AB - Introduction Reliable serum creatinine measurements are of vital importance for
the correct classification of chronic kidney disease and early identification of
kidney injury. The National Kidney Disease Education Programme working group and
other groups have defined clinically acceptable analytical limits for creatinine
methods. The aim of this study was to re-evaluate the performance of routine
creatinine methods in the light of these defined limits so as to assess their
suitability for clinical practice. Method In collaboration with the Dutch
External Quality Assurance scheme, six frozen commutable samples, with a
creatinine concentration ranging from 80 to 239 MUmol/L and traceable to isotope
dilution mass spectrometry, were circulated to 91 laboratories in four European
countries for creatinine measurement and estimated glomerular filtration rate
calculation. Two out of the six samples were spiked with glucose to give high and
low final concentrations of glucose. Results Results from 89 laboratories were
analysed for bias, imprecision (%CV) for each creatinine assay and total error
for estimated glomerular filtration rate. The participating laboratories used
analytical instruments from four manufacturers; Abbott, Beckman, Roche and
Siemens. All enzymatic methods in this study complied with the National Kidney
Disease Education Programme working group recommended limits of bias of 5% above
a creatinine concentration of 100 MUmol/L. They also did not show any evidence
of interference from glucose. In addition, they also showed compliance with the
clinically recommended %CV of <=4% across the analytical range. In contrast, the
Jaffe methods showed variable performance with regard to the interference of
glucose and unsatisfactory bias and precision. Conclusion Jaffe-based creatinine
methods still exhibit considerable analytical variability in terms of bias,
imprecision and lack of specificity, and this variability brings into question
their clinical utility. We believe that clinical laboratories and manufacturers
should work together to phase out the use of relatively non-specific Jaffe
methods and replace them with more specific methods that are enzyme based.
PMID- 27496795
TI - Bone turnover marker reference intervals in young females.
AB - Background The use of bone turnover markers in clinical practice and research in
younger people is limited by the lack of normative data and understanding of
common causes of variation in bone turnover marker values in this demographic. To
appropriately interpret bone turnover markers, robust reference intervals
specific to age, development and sex are necessary. This study aimed to determine
reference intervals of bone turnover markers in females aged 16-25 years
participating in the Safe-D study. Methods Participants were recruited through
social networking site Facebook and were asked to complete an extensive, online
questionnaire and attend a site visit. Participants were tested for serum carboxy
terminal cross-linking telopeptide of type 1 collagen and total procollagen type
1 N-propeptide using the Roche Elecsys automated analyser. Reference intervals
were determined using the 2.5th to 97.5th percentiles of normalized bone turnover
marker values. Results Of 406 participants, 149 were excluded due to medical
conditions or medication use (except hormonal contraception) which may affect
bone metabolism. In the remaining 257 participants, the reference interval was
230-1000 ng/L for serum carboxy-terminal cross-linking telopeptide of type 1
collagen and 27-131 ug/L for procollagen type 1 N-propeptide. Both marker
concentrations were inversely correlated with age and oral contraceptive pill
use. Therefore, intervals specific to these variables were calculated.
Conclusions We defined robust reference intervals for cross-linking telopeptide
of type 1 collagen and procollagen type 1 N-propeptide in young females grouped
by age and contraceptive pill use. We examined bone turnover markers'
relationship with several lifestyle, clinical and demographic factors. Our
normative intervals should aid interpretation of bone turnover markers in young
females particularly in those aged 16 to 19 years where reference intervals are
currently provisional.
PMID- 27496796
TI - Diabetic macular oedema.
AB - Diabetic macular oedema, characterised by exudative fluid accumulation in the
macula, is the most common form of sight-threatening retinopathy in people with
diabetes. It affects one in 15 people with diabetes resulting in more than 20
million cases worldwide. Few epidemiological studies have been done to
specifically investigate risk factors for diabetic macular oedema, although poor
glycaemic and blood pressure control are associated with the presence and
development of the disorder. The pathophysiological processes begin with chronic
hyperglycaemia, and interplay between vascular endothelial growth factor (VEGF)
and inflammatory mediators. Non-invasive imaging using optical coherence
tomography has allowed clinicians to detect mild levels of diabetic macular
oedema in order to monitor progress and guide treatment. Although focal or grid
laser photocoagulation was the traditional mode of treatment, intraocular
pharmacotherapy with anti-VEGF agents is now the standard of care. However, these
therapies are expensive and resource intensive. Emerging therapeutic strategies
include improving efficacy and duration of VEGF suppression, targeting
alternative pathways such as inflammation, the kallikrein-kinin system, the
angiopoietin-Tie2 system, and neurodegeneration, and using subthreshold and
targeted laser therapy. Ongoing research should lead to improvements in
screening, diagnosis, and management of diabetic macular oedema.
PMID- 27496797
TI - Comparison of Nasal Potential Difference and Intestinal Current Measurements as
Surrogate Markers for CFTR Function.
AB - OBJECTIVES: Nasal potential difference (NPD) measurement is part of the
diagnostic criteria for cystic fibrosis (CF) and now used routinely as an
endpoint in clinical trials of correcting the basic defect in CF. Intestinal
current measurement (ICM), measured ex vivo on a rectal biopsy, has been used to
study cystic fibrosis transmembrane conductance regulator (CFTR) function but has
not been compared to NPD in the same subject in adults and children. The aim of
the study is to evaluate the potential usefulness of ICM as a marker of CFTR
function for treatment studies compared NPD in patients with CF and in healthy
control subjects. METHODS: ICM and NPD were performed on healthy controls and
patients with CF. The healthy adults were individuals undergoing routine
screening colonoscopy at the Beth Israel Deaconess Medical Center. The healthy
children were undergoing colonoscopy for suspicion of inflammation in Hadassah
Hebrew University Medical Center. The CF adults were recruited from Boston
Children's Hospital CF Center and CF Center Worcester Mass, the children with CF
from Hadassah CF Center. RESULTS: ICM measurements in healthy control subjects (n
= 16) demonstrated a mean (+/-SE) carbachol response of 16.0 (2.2) MUA/cm,
histamine response of 13.2 (2.1) MUA/cm and a forskolin response of 6.3 (2.0)
MUA/cm. Basal NPD of -15.9 (1.9) and response to Cl free + isoproterenol of -13.8
(2.0). These responses were inverted in CF subjects (n = 12) for ICM parameters
with carbachol response of -3.0 (0.5) MUA/cm, histamine -1.0 (0.8) MUA/cm and a
forskolin response of 0.5 (0.3) and also for NPD parameters; basal NPD of -42.2
(4.3) and response to Cl free + isoproterenol of 4.3 (0.7). Pearson correlation
test showed the comparability of ICM and NPD in assessing CFTR function.
CONCLUSIONS: ICM is equivalent to NPD in the ability to distinguish patients with
CF from controls and could be used as surrogate markers of CFTR activity in
treatment protocols.
PMID- 27496798
TI - Prevalence and Significance of Autoantibodies in Children With Acute Liver
Failure.
AB - OBJECTIVES: The purpose of the present study is to estimate autoantibody (auto
AB) frequency, clinical characteristics, and 21-day outcome of participants in
the Pediatric Acute Liver Failure Study Group (PALFSG) by antinuclear antibody,
smooth muscle antibody, and liver-kidney microsomal (LKM) antibody status.
METHODS: Auto-ABs were determined at local and/or central laboratories. Subjects
were assigned to autoimmune hepatitis (AIH), indeterminate, and other diagnoses
groups. RESULTS: Between 1999 and 2010, 986 subjects were enrolled in the PALFSG.
At least 1 auto-AB result was available for 722 (73.2%). At least 1 auto-AB was
positive for 202 (28.0%). Diagnoses for auto-AB+ subjects were AIH (63),
indeterminate (75), and other (64). Auto-ABs were more common in Wilson disease
(12/32, 37.5%) compared with other known diagnoses (52/253, 20.6%, P = 0.03).
LKM+ subjects were younger (median 2.4 vs 9.1 years, P < 0.001) and more likely
to undergo liver transplantation (53.3% vs 31.4% P = 0.02) than other auto
AB+/LKM- subjects. Steroid treatment of subjects who were auto-AB+ was not
significantly associated with survival and the subgroup with known diagnoses
other than AIH had a higher risk of death. CONCLUSIONS: Auto-ABs are common in
children with acute liver failure, occurring in 28%. Auto-AB+ subjects have
similar outcomes to auto-AB negative subjects. LKM+ children are younger and more
likely to undergo liver transplantation compared with other auto-AB+ subjects.
Although auto-AB may indicate a treatable condition, positivity does not
eliminate the need for a complete diagnostic evaluation because auto-ABs are
present in other conditions. The significance of auto-AB in pediatric acute liver
failure remains uncertain, but LKM+ appears to identify a unique population of
children who merit further study.
PMID- 27496799
TI - Factors Associated With Bleeding Secondary to Rupture of Esophageal Varices in
Children and Adolescents With Cirrhosis.
AB - OBJECTIVE: Bleeding of esophageal varices is the main cause of morbidity and
mortality in children with portal hypertension. It is important to understand the
factors related with a bleeding episode to evaluate more effective primary
prophylaxis. The present study aims to describe the endoscopic and laboratory
findings associated with upper gastrointestinal bleeding (UGIB) secondary to
esophageal varices. METHOD: A cross-sectional study with 103 children and
adolescents with cirrhosis, divided into a group that had experienced an episode
of upper UGIB (35 patients) and a group without a history of UGIB (68 patients),
was carried out. The esophageal and gastric varices were classified, and the
portal hypertensive gastropathy, laboratory findings, and Child-Pugh
classification were measured. RESULTS: Factors observed in univariate analysis to
be associated with UGIB were the presence of esophageal varices of medium caliber
or larger, portal hypertensive gastropathy, presence of red spots on esophageal
varices, Child-Pugh class B or C, and hypoalbuminemia (P < 0.05). After
multivariate logistic regression analysis, the significant factors were the
presence of red spots on esophageal varices and the presence of gastric varices.
When separated the autoimmune hepatitis, nonbiliary atresia patients (all
patients except the patients with biliary atresia), and biliary atresia groups
the findings in the univariate analysis were the presence of esophageal varices
of medium or larger caliber, presence of red spots on varices, and presence of
gastric varices in the autoimmune hepatitis patients and nonbiliary atresia
patients and presence of red spots on esophageal varices, presence of gastric
varices, and Child-Pugh classification B or C in biliary atresia group (P <
0.05). After multivariate logistic regression analysis, no statistical
significance was found for any factor analyzed in any groups. CONCLUSIONS: The
presence of gastric varices and red spots on esophageal varices were related to
episodes of UGIB secondary to rupture of esophageal varices. When these findings
are observed, indications for endoscopic primary prophylaxis should be evaluated.
More studies are, however, necessary to better understand this problem.
PMID- 27496800
TI - There Is No Iron in Human Milk.
PMID- 27496802
TI - An examination of femicides in Peru between 2009 and 2014.
PMID- 27496801
TI - The role of adaptive bone formation in the etiology of stress fracture.
AB - Stress fractures are common injuries with load-bearing activities. Stress
fractures have been reported in the scientific literature for over a century;
however, the etiology continues to be investigated with important distinctions
made between the contributions of the tissue-level processes of bone remodeling
and modeling. In response to novel repetitive loading, increased bone remodeling
may serve to replace fatigue-damaged bone while at the same time creating
temporary porosity. Much attention has been given to the role of remodeling in
the etiology of stress fracture; however, the role of bone modeling has received
less attention. Modest increases in modeling, via bone formation on the
periosteal surface of long bones in response to mechanical loading, greatly
increases the fatigue resistance of bone. Thus, enhancing this adaptive bone
formation is a promising target for stress fracture prevention, and a focus on
adaptive bone formation may reveal novel risk factors for stress fracture.
PMID- 27496803
TI - Theoretical modeling of multiprotein complexes by iSPOT: Integration of small
angle X-ray scattering, hydroxyl radical footprinting, and computational docking.
AB - Structural determination of protein-protein complexes such as multidomain nuclear
receptors has been challenging for high-resolution structural techniques. Here,
we present a combined use of multiple biophysical methods, termed iSPOT, an
integration of shape information from small-angle X-ray scattering (SAXS),
protection factors probed by hydroxyl radical footprinting, and a large series of
computationally docked conformations from rigid-body or molecular dynamics (MD)
simulations. Specifically tested on two model systems, the power of iSPOT is
demonstrated to accurately predict the structures of a large protein-protein
complex (TGFbeta-FKBP12) and a multidomain nuclear receptor homodimer (HNF
4alpha), based on the structures of individual components of the complexes.
Although neither SAXS nor footprinting alone can yield an unambiguous picture for
each complex, the combination of both, seamlessly integrated in iSPOT, narrows
down the best-fit structures that are about 3.2A and 4.2A in RMSD from their
corresponding crystal structures, respectively. Furthermore, this proof-of
principle study based on the data synthetically derived from available crystal
structures shows that the iSPOT-using either rigid-body or MD-based flexible
docking-is capable of overcoming the shortcomings of standalone computational
methods, especially for HNF-4alpha. By taking advantage of the integration of
SAXS-based shape information and footprinting-based protection/accessibility as
well as computational docking, this iSPOT platform is set to be a powerful
approach towards accurate integrated modeling of many challenging multiprotein
complexes.
PMID- 27496806
TI - Pancreatic tail schwannoma.
PMID- 27496807
TI - [Multidisciplinary units in tertiary referral hospitals to improve management of
Wilson disease].
PMID- 27496805
TI - Peroxisome proliferator-activated receptor alpha-dependent renoprotection of
murine kidney by irbesartan.
AB - Activation of renal peroxisome proliferator-activated receptor alpha (PPARalpha)
is renoprotective, but there is no safe PPARalpha activator for patients with
chronic kidney disease (CKD). Studies have reported that irbesartan (Irbe), an
angiotensin II receptor blocker (ARB) widely prescribed for CKD, activates
hepatic PPARalpha. However, Irbe's renal PPARalpha-activating effects and the
role of PPARalpha signalling in the renoprotective effects of Irbe are unknown.
Herein, these aspects were investigated in healthy kidneys of wild-type (WT) and
Ppara-null (KO) mice and in the murine protein-overload nephropathy (PON) model
respectively. The results were compared with those of losartan (Los), another ARB
that does not activate PPARalpha. PPARalpha and its target gene expression were
significantly increased only in the kidneys of Irbe-treated WT mice and not in KO
or Los-treated mice, suggesting that the renal PPARalpha-activating effect was
Irbe-specific. Irbe-treated-PON-WT mice exhibited decreased urine protein
excretion, tubular injury, oxidative stress (OS), and pro-inflammatory and
apoptosis-stimulating responses, and they exhibited maintenance of fatty acid
metabolism. Furthermore, the expression of PPARalpha and that of its target mRNAs
encoding proteins involved in OS, pro-inflammatory responses, apoptosis and fatty
acid metabolism was maintained upon Irbe treatment. These renoprotective effects
of Irbe were reversed by the PPARalpha antagonist MK886 and were not detected in
Irbe-treated-PON-KO mice. These results suggest that Irbe activates renal
PPARalpha and that the resultant increased PPARalpha signalling mediates its
renoprotective effects.
PMID- 27496804
TI - miR-200b induces cell cycle arrest and represses cell growth in esophageal
squamous cell carcinoma.
AB - miR-200b is a pleiotropically acting microRNA in cancer progression, representing
an attractive therapeutic target. We previously identified miR-200b as an
invasiveness repressor in esophageal squamous cell carcinoma (ESCC), whereas
further understanding is warranted to establish it as a therapeutic target. Here,
we show that miR-200b mitigates ESCC cell growth by inducing G2-phase cell cycle
arrest and apoptosis. The expression/activation of multiple key cell cycle
regulators such as CDK1, CDK2, CDK4 and Cyclin B, and the Wnt/beta-Catenin
signaling are modulated by miR-200b. We identified CDK2 and PAF (PCNA-associated
factor), two important tumor-promoting factors, as direct miR-200b targets in
ESCC. Correlating with the frequent loss of miR-200b in ESCC, both CDK2 and PAF
levels are significantly increased in ESCC tumors compared to case-matched normal
tissues (n = 119, both P < 0.0001), and correlate with markedly reduced survival
(P = 0.007 and P = 0.041, respectively). Furthermore, CDK2 and PAF are also
associated with poor prognosis in certain subtypes of breast cancer (n = 1802)
and gastric cancer (n = 233). Although CDK2 could not significantly mediate the
biological function of miR-200b, PAF siRNA knockdown phenocopied while restored
expression of PAF abrogated the biological effects of miR-200b on ESCC cells.
Moreover, PAF was revealed to mediate the inhibitory effects of miR-200b on
Wnt/beta-Catenin signaling. Collectively, the pleiotropic effects of miR-200b in
ESCC highlight its potential for therapeutic intervention in this aggressive
disease.
PMID- 27496808
TI - Ileocolic intussusception of ileal lipoma as a cause of lower gastrointestinal
bleeding.
PMID- 27496810
TI - Measurement in Family Nursing: Established Instruments and New Directions.
PMID- 27496809
TI - Acute hepatitis due to hepatitis E virus after raw meat consumption.
PMID- 27496811
TI - Development and Psychometric Testing of the Iceland-Family Illness Beliefs
Questionnaire.
AB - Illness beliefs affect how individuals and families deal with illness. A valid
and reliable instrument has not yet been developed to measure "illness beliefs"
in family nursing research and clinical practice. This article describes the
purpose, reliability, validity, and the potential clinical and research
applications of a new instrument, the Iceland-Family Illness Beliefs
Questionnaire (ICE-FIBQ). The ICE-FIBQ is a short, self-report measure of an
individual's beliefs about illness. Drawing from an advanced nursing practice
model called the Illness Beliefs Model, the instrument was developed to measure
illness beliefs about (a) cause of illness, that is, etiology; (b) control of
illness on family and control of family on illness; (c) effect of illness on the
individual and family; (d) illness suffering; and (e) support received from
health care professionals during illness. The instrument was tested on 139 family
caregivers of adolescents/youth with an illness or a disorder. Exploratory factor
analysis reduced the original questionnaire from eight to seven items with a one
factor solution (Cronbach's alpha = .780). Confirmatory factor analysis supported
the one-factor solution (Cronbach's alpha = .789). Further research is needed to
determine concurrent validity with other illness belief/illness perception scales
and if the instrument is sensitive to capture change in illness beliefs following
family nursing intervention.
PMID- 27496813
TI - Reply to the Letter to the Editor entitled "Acute heart failure from
noncompaction requiring emergency heart transplantation".
PMID- 27496814
TI - Acute heart failure from noncompaction requiring emergency heart transplantation.
PMID- 27496815
TI - JRSM in a Brexit world.
PMID- 27496816
TI - Early 18th century evidence synthesis.
PMID- 27496817
TI - A statistical note on Karl Pearson's 1904 meta-analysis.
PMID- 27496818
TI - A statistical note on the analysis of the 1948 MRC streptomycin trial.
PMID- 27496822
TI - Serum proatrial natriuretic peptide does not increase with higher systolic blood
pressure in obese men.
AB - OBJECTIVE: Obese persons have low circulating natriuretic peptide (NP)
concentrations. It has been proposed that this 'natriuretic handicap' could play
a role in obesity-related hypertension. The normal physiological response of the
NP system to an increase in blood pressure (BP) is an increase in NP secretion
with concomitant higher circulating NP concentrations. In this study, we
investigated whether higher BP would also be related to higher circulating NP
concentrations in obese men; furthermore, we verified that BP had affected the
hearts of our study participants, by determining left ventricular mass (LVM).
METHODS: We examined 103 obese healthy medication-free men. We measured 24-hour
ambulatory BP (ABP). LVM was calculated using the Cornell voltage-duration
product method. Fasting serum concentrations of midregional proatrial NP (MR
proANP), a surrogate for active ANP, were measured. Linear regression analysis
was used to calculate age-adjusted standardised regression coefficients (beta).
RESULTS: LVM and BP increased across systolic ABP quartiles (mean LVM+/-SD:
1599.1+/-387.2 mm ms in first vs 2188.5+/-551.3 mm ms in fourth quartile,
p<0.001; mean systolic ABP+/-SD: 114.5+/-4.2 mm Hg in first vs 149.0+/-7.7 mm Hg
in fourth quartile, p<0.001). Systolic ABP was robustly associated with LVM
(beta=0.48, p<0.001). Despite evidence of BP-related increases in LVM, serum MR
proANP was negatively associated with systolic ABP (beta=-0.32, p=0.004) and with
diastolic ABP (beta=-0.45, p<0.001). CONCLUSIONS: Contrary to known physiological
BP responses, MR-proANP was negatively associated with ABP in our study. This
suggests that a low amount of circulating NPs could play a role in the early
stage of obesity-related hypertension.
PMID- 27496823
TI - It is not just comfort: waterproof casting increases physical functioning in
children with minimally angulated distal radius fractures.
AB - : Waterproof casting has been reported to increase patient comfort and
satisfaction, and decrease skin irritation. There are no available data on the
influence of waterproof casting materials on physical function in pediatric
patients. Our aim was to determine whether the use of waterproof casting would
result in faster recovery of physical function while maintaining similar clinical
outcomes as those obtained with nonwaterproof materials. Twenty-six children with
nonangulated or minimally angulated distal radius fractures were assigned
randomly to initially receive a short-arm cast made of one of two optional
materials: a hybrid mesh material with a waterproof lining or fiberglass with a
nonwaterproof skin protector. Two weeks later, the initial cast was removed and
replaced with a short-arm cast made of the alternative option. We compared the
rate of fracture displacement, physical function, pain, skin changes, itchiness,
and patient satisfaction. No evidence of displacement was found in either group.
The mean Activities Scale for Kids - Performance (ASK-P) (physical function)
score was 10% higher during the period of time when a waterproof cast was used
(P=0.04). When a waterproof cast was used during the first 2 weeks of treatment,
the mean total ASK-P scores were 23% higher than that when a nonwaterproof one
was used during the same period of time (P=0.003). Patients who received a
waterproof cast as the initial treatment reported lower functional scores overall
and in almost every domain of the ASK-P once they were in a nonwaterproof one;
similarly, those who received a nonwaterproof cast as the initial treatment
reported higher functional scores overall and in every domain of the ASK-P once
they were in a waterproof cast. Compared with a nonwaterproof cast, the use of
waterproof casting resulted in comparable levels of pain, itchiness, skin
irritability, and overall patient satisfaction. The results of this randomized,
cross-over trial suggest that the use of waterproof casting material for the
treatment of nondisplaced or minimally displaced distal radius fractures in
children can result in a faster recovery of physical function, while providing
comparable stability, pain, itchiness, skin irritability, and overall patient
satisfaction. LEVEL OF EVIDENCE: II.
PMID- 27496824
TI - Alemtuzumab in paediatric kidney transplantation, five years' experience at the
Pablo Tobon Uribe Hospital in Medellin, Colombia.
PMID- 27496825
TI - Immediate ICU Care for Patients Following Aortic Arch Surgery.
AB - Patients undergoing aortic arch surgery are at high risk for stroke, delirium,
low cardiac output, respiratory failure, renal failure, and coagulopathy. A
significantly higher mortality is seen in patients experiencing any of these
complications when compared with those without complications. As surgical,
perfusion, and anesthetic techniques improve, the incidence of major
complications have decreased. A recent paradigm shift in cardiac surgery has
focused on rapid postoperative recovery, and a similar change has affected the
care of patients after arch surgery. Nevertheless, a small subset of patients
experience significant morbidity and mortality after aortic arch surgery, and
rapid identification of any organ dysfunction and appropriate supportive care is
critical in these patients. In this article, the current state of postoperative
care of the patient after open aortic arch surgery will be reviewed.
PMID- 27496826
TI - Understanding How Overweight and Obese Emerging Adults Make Lifestyle Choices.
AB - : To better understand health-related decision making among overweight and obese
emerging adults. DESIGN AND METHODS: A cross-sectional design was used in the
parent study involving overweight and obese emerging adults, ages 18-29 years.
The goal of the parent study was to screen participants' diabetes risk and
identify characteristics of emerging adults with prediabetes (N=107). A sub
sample of respondents (n=34) from the parent study were invited to participate in
focus group interviews depending on whether they had prediabetes (three groups)
or they did not have prediabetes (four groups). Each focus group interview lasted
90-120 minutes following a semi-structured interview guide. Conventional content
analysis was used in the data analysis. Because of the similarities between
participants with and without prediabetes, the findings were synthesized and
reported in the aggregate. Moreover, during the analysis, the authors decided
that rational choice theory provided a useful organizing structure for presenting
the data. RESULTS: Emerging adults' behavioral decisions were rational reactions
to their personal competence, perception of health, environment, and availability
of resources to handle problems. Calculation of trade-offs and estimations of
resource availability were often used when making decisions. CONCLUSIONS:
Emerging adults choose unhealthy behaviors due to inaccurate information and
insufficient competence to practice healthy lifestyles rather than because of
laziness or being irrational. PRACTICE IMPLICATIONS: Behavioral interventions for
emerging adults need to help them develop skills to enhance health literacy and
problem solving, thereby enhancing their awareness of available resources and
decreasing the perceived cost of making healthy choices.
PMID- 27496827
TI - Statins in the Management of Pediatric Dyslipidemia.
AB - Hypercholesterolemia is a major concern in the USA, with studies identifying
children as young as 2years old with early-stage atherosclerosis. Genetics play a
major role in the dyslipidemia of children, but other factors, such as diet and
lack of physical activity, confound the problem. Familial hypercholesterolemia
(FH) is a genetic condition that causes lifelong elevations in low-density
lipoprotein cholesterol (LDL-C). The heterozygous form of the disease affects
around 1 in 200 people, and the homozygous form of the disease affects around 1
in 160,000-300,000 people. Early identification and appropriate management of
patients with FH are essential to reduce cardiovascular disease morbidity and
mortality. Consequently, US dyslipidemia guidelines recommend routine screening
of all children aged 9-11years, and that LDL-C levels should be <110mg/dL in
children and adolescents. The primary management strategy in all children with
dyslipidemia is diet and lifestyle; a healthy diet (including fruits, vegetables,
fish, and whole grains) and increased physical activity should be encouraged.
Most patients with FH will also require pharmacotherapy to reduce LDL-C levels to
<=130mg/dL. Statins are recommended as first-line therapy due to their proven
efficacy in reducing LDL-C and improving other lipid parameters in children. They
have also been shown to have a positive effect on atherosclerosis. Safety is of
particular concern with children; however, studies have so far shown that the
side-effect profile of statins in children is similar to that in adults. Despite
improvements in disease management, FH remains underdiagnosed and undertreated,
highlighting the need for greater awareness and understanding.
PMID- 27496829
TI - "Pain Is What the Patient Says It Is": Nurse-Patient Communication, Information
Seeking, and Pain Management.
AB - Nurse-patient conversations about pain management are complex. Given recent
increases in prescription pain pill abuse, such interactions merit scholarly
attention. In-depth interviews with 21 nurses were conducted to explicitly
explore nurses' information seeking about pain. The participants in this study
gathered pain information from patients through a variety of means and reported
facing challenges and dilemmas when communicating with patients about pain
management and medicinal preferences. These results have important implications
for nurses, patient outcomes, and the broader health-care system and imply that
continued educational and intervention efforts are essential in this complicated
communicative context.
PMID- 27496828
TI - "Good Passengers and Not Good Passengers:" Adolescent Drivers' Perceptions About
Inattention and Peer Passengers.
AB - PURPOSE: The purpose of this qualitative focus group elicitation research study
was to explore teen driver perceptions of peer passengers and driver inattention.
DESIGN & METHODS: We utilized focus groups for data collection and content
analysis to analyze the data, both of which were guided by the theory of planned
behavior. We conducted 7 focus groups with 30 teens, ages 16-18, licensed for
<=1year to examine attitudes, perceived behavioral control, and norms related to
driving inattention and peer passengers. RESULTS: The sample was 50% male, mean
age 17.39 (SD 0.52) with mean length of licensure 173.7days (SD 109.2). Three
themes emerged: 1) "Good and not good" passengers; 2) Passengers and technology
as harmful and helpful; and 3) The driver is in charge. CONCLUSIONS: While
passengers can be a source of distraction, our participants also identified
passenger behaviors that reduced risk, such as assistance with technology and
guidance for directions. PRACTICAL IMPLICATIONS: An understanding of teens'
perceptions of peer passengers can contribute to the development of effective
interventions targeting teen driver inattention. Nurses are well-positioned to
contribute to these teen crash prevention efforts.
PMID- 27496830
TI - As Zika cases mount, patients seek advice from healthcare teams.
PMID- 27496833
TI - Correction.
PMID- 27496831
TI - New OSHA document reviews hazardous-drug safety for employees.
PMID- 27496834
TI - Medicare delays mandate on claims for unused part of drug doses.
PMID- 27496836
TI - Formalized mentorship program for newly hired pharmacists.
PMID- 27496837
TI - Factors influencing pursuit of postgraduate year 2 pharmacy residency training.
PMID- 27496838
TI - Lessons learned from summer introductory pharmacy practice experiences at an
academic medical center.
PMID- 27496839
TI - Models for student organizations in multicampus schools of pharmacy.
PMID- 27496840
TI - Pharmacy: Profession of hope.
PMID- 27496842
TI - Inaugural Address of the Incoming President: Pharmacy's true north.
PMID- 27496841
TI - Identifying and optimizing communication in patients with hearing loss.
PMID- 27496843
TI - 2016 Report of the President and Chair of the Board.
PMID- 27496844
TI - 2016 Report of the Chief Executive Officer.
PMID- 27496847
TI - ASHP Award of Excellence.
PMID- 27496846
TI - Of philosophers and pharmacists.
PMID- 27496851
TI - ASHP policy on the acceptance of advertising.
PMID- 27496852
TI - Impact of a store-and-forward teledermatology intervention versus usual care on
delay before beginning treatment: A pragmatic cluster-randomized trial in
ambulatory care.
AB - Introduction In France, 66% of patients forego getting specialized care by
dermatologists because of difficulty obtaining appointments. Store-and-forward
teledermatology could improve how promptly treatment begins by reducing the delay
in obtaining a specialist's opinion. In this study, we compared the delay before
care between general practitioners (GPs) using a store-and-forward
teledermatology intervention and GPs addressing their patients with a standard
referral letter. Methods We performed an open-label, pragmatic cluster-randomized
controlled trial with two parallel arms. GP clinics in Paris (France) were
randomly assigned to use either teledermatology referral (use of electronics to
send clinical images taken using a mobile phone) or conventional referral (using
standard letters) to care for patients for whom a dermatologist's advice was
needed for the diagnosis or treatment of skin lesions. Dermatologists integrated
responses to teledermatology requests in their usual schedule. Patients were
followed up for three months. Primary outcome was the delay, in days, between the
GP's consultation and a reply by the specialist allowing treatment to begin.
Analyses were adjusted for clustering of GPs and identities of dermatologists.
Results Between February and June 2014, 103 patients were included in the study
(53 patients of 20 GPs in the intervention group). The median delay between the
initial GP's consultation and the reply allowing for treatment to begin was four
days in the intervention group and 40 days in the control group (adjusted hazard
ratio = 2.55; p < 0.011). Discussion We showed that a simple store-and-forward
teledermatology intervention significantly reduced the delay before beginning
care (ClinicalTrials.gov identifier: NCT02122432).
PMID- 27496854
TI - Crosstalk between E2f1 and c-Myc mediates hepato-protective effect of royal jelly
on taxol-induced damages.
AB - Previous histopathological studies have shown the hepatotoxicity of paclitaxel
(TXL). However, there is little known about the molecular pathway(s) of TXL
induced hepatotoxicity. Therefore, this study aimed to uncover the role of two
transcription factors in the TXL-induced hepatotoxicity. Moreover, the hepato
protective effect of royal jelly (RJ) on TXL-induced toxicity was investigated.
Wistar rats were divided into control and test groups. The test groups along with
TXL received various doses of RJ (0, 50, 100 and 150 mg/kg, body weight).
Biochemical hepatic functional assays, histopathological studies and hepatic
superoxide dismutase level were determined. Additionally, the expression of E2f1
and cellular-myelocytomatosis (c-Myc) at messenger RNA (mRNA) level in the liver
was evaluated. The hepatic functional biomarkers showed a significant ( p < 0.05)
elevation in the TXL-received animals, while RJ administration for 28 days
resulted in a remarkable reduction in TXL-elevated alkaline phosphatase, alanine
transaminase and lactate dehydrogenase levels. The TXL-treated animals showed a
significant ( p < 0.05) up-regulation of E2f1 and down-regulation of c-Myc at
mRNA level, respectively. RJ lowered the expression of E2f1 while enhanced the
expression of c-Myc in a dose-dependent manner. Our data suggest the hepato
protective effects of RJ on TXL-induced toxicity, which may attribute to a clear
crosstalk between E2f1 and c-Myc as two regulators of liver growth.
PMID- 27496853
TI - Maternal feed restriction during pregnancy in Wistar rats: Evaluation of
offspring using classical and immunoteratology protocols.
AB - Studies have revealed that impairment of the pregnant body weight reduces the
fetal body weight and causes minor changes in skeletal development. The aim of
the present study was to assess the effects of maternal feed restriction during
pregnancy in offspring immune system development. Pregnant Wistar rats were
distributed into 5 groups: 1 control in which dams received food ad libitum and 4
experimental groups in which dams were fed restricted amounts of rodent ration
(16, 12, 9, or 6 g/rat/day) from the 6th to 17th gestation day. Teratogenicity
was assessed using classical teratological evaluation and developmental
immunotoxicology protocols. Maternal body weight gain, fetus weight, and placenta
weight were reduced for feed-restricted females from the groups fed 12, 9, and 6
g/rat/day ( p < 0.05). No pup mortality was observed immediately after cesarean
sections among the groups, and no visceral or skeletal malformations were
detected. An immunoteratological study revealed an increase in the relative
weight of the thymus and an increase in the phorbol myristate-acetate solution
induced hydrogen peroxide release by inflammatory cells in 21-day-old pups.
Alterations in the delayed-type hypersensitivity response and the humoral immune
response against sheep red blood cells were observed in pups from feed-restricted
mothers. Feed restriction in Wistar rats during organogenesis did not promote
structural malformations but resulted in offspring with lower birth weights and
promoted significant changes in the immune responses of the rat pups.
PMID- 27496855
TI - Comparison of Dabigatran and Warfarin in Patients With Atrial Fibrillation and
Valvular Heart Disease: The RE-LY Trial (Randomized Evaluation of Long-Term
Anticoagulant Therapy).
AB - BACKGROUND: The RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant
Therapy) compared dabigatran 150 and 110 mg twice daily with warfarin in 18 113
patients with atrial fibrillation. Those with prosthetic heart valves,
significant mitral stenosis, and valvular heart disease (VHD) requiring
intervention were excluded. Others with VHD were included. METHODS: This is a
post hoc analysis of the RE-LY trial. RESULTS: There were 3950 patients with any
VHD: 3101 had mitral regurgitation, 1179 with tricuspid regurgitation, 817 had
aortic regurgitation, 471 with aortic stenosis, and 193 with mild mitral
stenosis. At baseline, patients with any VHD had more heart failure, coronary
disease, renal impairment, and persistent atrial fibrillation. Patients with any
VHD had higher rates of major bleeds (hazard ratio [HR], 1.32; 95% confidence
interval [CI], 1.16-1.5) but similar stroke or systemic embolism event rates (HR,
1.09; 95% CI, 0.88-1.33). For patients receiving dabigatran 110 mg, major bleed
rates were lower than for patients taking warfarin (HR, 0.73; 95% CI, 0.56-0.95
with VHD; HR, 0.84; 95% CI, 0.71-0.99 without VHD), and major bleed rates for
dabigatran 150 mg were similar to those for warfarin in patients with VHD (HR,
0.82; 95% CI, 0.64-1.06) or without VHD (HR, 0.98; 95% CI, 0.83-1.15). For
dabigatran 150 mg, stroke/systemic embolic event rates were lower compared with
warfarin in those with VHD (HR, 0.59; 95% CI, 0.37-0.93) and those without VHD
(HR, 0.67; 95% CI, 0.52-0.86), and stroke/systemic embolic event rates were
similar for warfarin and dabigatran 110 mg regardless of the presence of VHD (HR,
0.97; 95% CI, 0.65-1.45; and HR, 0.88; 95% CI, 0.70-1.10). Intracranial bleeds
and death rates for dabigatran 150 and 110 mg were lower compared with warfarin
independently of the presence of VHD. CONCLUSIONS: The presence of any VHD did
not influence the comparison of dabigatran with warfarin. CLINICAL TRIAL
REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
PMID- 27496856
TI - Long-Term Outcomes of the Ross Procedure Versus Mechanical Aortic Valve
Replacement: Propensity-Matched Cohort Study.
AB - BACKGROUND: The ideal aortic valve substitute in young and middle-aged adults
remains unknown. We sought to compare the long-term outcomes of patients
undergoing the Ross procedure and those receiving a mechanical aortic valve
replacement (AVR). METHODS: From 1990 to 2014, 258 patients underwent a Ross
procedure and 1444 had a mechanical AVR at a single institution. Patients were
matched into 208 pairs through the use of a propensity score. Mean age was 37.2+/
10.2 years, and 63% were male. Mean follow-up was 14.2+/-6.5 years. RESULTS:
Overall survival was equivalent (Ross versus AVR: hazard ratio, 0.91, 95%
confidence interval, 0.38-2.16; P=0.83), although freedom from cardiac- and valve
related mortality was improved in the Ross group (Ross versus AVR: hazard ratio,
0.22; 95% confidence interval, 0.034-0.86; P=0.03). Freedom from reintervention
was equivalent after both procedures (Ross versus AVR: hazard ratio, 1.86; 95%
confidence interval, 0.76-4.94; P=0.18). Long-term freedom from stroke or major
bleeding was superior after the Ross procedure (Ross versus AVR: hazard ratio,
0.09; 95% confidence interval, 0.02-0.31; P<0.001). CONCLUSIONS: Long-term
survival and freedom from reintervention were comparable between the Ross
procedure and mechanical AVR. However, the Ross procedure was associated with
improved freedom from cardiac- and valve-related mortality and a significant
reduction in the incidence of stroke and major bleeding. In specialized centers,
the Ross procedure represents an excellent option and should be considered for
young and middle-aged adults undergoing AVR.
PMID- 27496858
TI - Ross Procedure for Aortic Valve Replacement in Young Adults: Preferred Procedure
or "Double, Double Toil and Trouble"?
PMID- 27496860
TI - Healthy and wellbeing activities' promotion using a Big Data approach.
AB - The aging population and economic crisis specially in developed countries have as
a consequence the reduction in funds dedicated to health care; it is then
desirable to optimize the costs of public and private healthcare systems,
reducing the affluence of chronic and dependent people to care centers; promoting
healthy lifestyle and activities can allow people to avoid chronic diseases as
for example hypertension. In this article, we describe a system for promoting an
active and healthy lifestyle for people and to recommend with guidelines and
valuable information about their habits. The proposed system is being developed
around the Big Data paradigm using bio-signal sensors and machine-learning
algorithms for recommendations.
PMID- 27496859
TI - Implementation of Birth-Cohort Testing for Hepatitis C Virus.
AB - Hepatitis C virus infection affects approximately 2.2 to 3.2 million Americans.
In 2012, the Centers for Disease Control and Prevention recommended a one-time
antibody test of all persons belonging to the 1945-1965 birth cohort. Efforts to
implement this recommendation in clinical settings are in their infancy; this
case study report therefore seeks to share the experiences of three sites that
implemented interventions to increase birth-cohort testing through participation
in the Birth-cohort Evaluation to Advance Screening and Testing for Hepatitis C.
At each site, project managers completed standardized questionnaires about their
implementation experiences, and a qualitative analysis was conducted of the
responses. The testing interventions used in-person recruitment, mail
recruitment, and an electronic health record prompt. Sites reported that early
efforts to obtain stakeholder buy-in were critical to effectively implement and
sustain interventions and that the intervention required additional staffing
resources beyond those being used for risk-based testing. In each case,
administrative barriers were more extensive than anticipated. For the electronic
health record-based intervention, technological support was critical in achieving
study goals. Despite these barriers, interventions in all sites were successful
in increasing rates of testing and case identification, although future studies
will need to evaluate the relative costs and benefits of each intervention.
PMID- 27496861
TI - Effect of technology on aging perception.
AB - Technology can assist older adults to maintain an active lifestyle. To better
understand the effect that technology has on aging perception, we conducted two
studies. In the first study, through supraliminal priming, we analyzed the
effects of aging- and technology-related stimuli on age estimation. In the second
study, we conducted a technological intervention with a group of elders who used
four interactive devices and analyzed effects on perceived aging. Results showed
that technology-related stimuli did not affect estimated age. From the second
study, we generated a sociotechnical model that explains the processes connecting
technology use with successful aging. We concluded that the use of technology
affects aging perception, although it depends on whether the elder people have a
proactive attitude toward their aging process a priori.
PMID- 27496857
TI - Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an
Inflammatory Monocyte Response in Humans.
AB - BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a prevalent, independent
cardiovascular risk factor, but the underlying mechanisms responsible for its
pathogenicity are poorly defined. Because Lp(a) is the prominent carrier of
proinflammatory oxidized phospholipids (OxPLs), part of its atherothrombosis
might be mediated through this pathway. METHODS: In vivo imaging techniques
including magnetic resonance imaging, (18)F-fluorodeoxyglucose uptake positron
emission tomography/computed tomography and single-photon emission computed
tomography/computed tomography were used to measure subsequently atherosclerotic
burden, arterial wall inflammation, and monocyte trafficking to the arterial
wall. Ex vivo analysis of monocytes was performed with fluorescence-activated
cell sorter analysis, inflammatory stimulation assays, and transendothelial
migration assays. In vitro studies of the pathophysiology of Lp(a) on monocytes
were performed with an in vitro model for trained immunity. RESULTS: We show that
subjects with elevated Lp(a) (108 mg/dL [50-195 mg/dL]; n=30) have increased
arterial inflammation and enhanced peripheral blood mononuclear cells trafficking
to the arterial wall compared with subjects with normal Lp(a) (7 mg/dL [2-28
mg/dL]; n=30). In addition, monocytes isolated from subjects with elevated Lp(a)
remain in a long-lasting primed state, as evidenced by an increased capacity to
transmigrate and produce proinflammatory cytokines on stimulation (n=15). In
vitro studies show that Lp(a) contains OxPL and augments the proinflammatory
response in monocytes derived from healthy control subjects (n=6). This effect
was markedly attenuated by inactivating OxPL on Lp(a) or removing OxPL on
apolipoprotein(a). CONCLUSIONS: These findings demonstrate that Lp(a) induces
monocyte trafficking to the arterial wall and mediates proinflammatory responses
through its OxPL content. These findings provide a novel mechanism by which Lp(a)
mediates cardiovascular disease. CLINICAL TRIAL REGISTRATION: URL:
http://www.trialregister.nl. Unique identifier: NTR5006 (VIPER Study).
PMID- 27496862
TI - Detecting hospital-acquired infections: A document classification approach using
support vector machines and gradient tree boosting.
AB - Hospital-acquired infections pose a significant risk to patient health, while
their surveillance is an additional workload for hospital staff. Our overall aim
is to build a surveillance system that reliably detects all patient records that
potentially include hospital-acquired infections. This is to reduce the burden of
having the hospital staff manually check patient records. This study focuses on
the application of text classification using support vector machines and gradient
tree boosting to the problem. Support vector machines and gradient tree boosting
have never been applied to the problem of detecting hospital-acquired infections
in Swedish patient records, and according to our experiments, they lead to
encouraging results. The best result is yielded by gradient tree boosting, at
93.7 percent recall, 79.7 percent precision and 85.7 percent F1 score when using
stemming. We can show that simple preprocessing techniques and parameter tuning
can lead to high recall (which we aim for in screening patient records) with
appropriate precision for this task.
PMID- 27496863
TI - A prediction model of blood pressure for telemedicine.
AB - This paper presents a new study based on a machine learning technique,
specifically an artificial neural network, for predicting systolic blood pressure
through the correlation of variables (age, BMI, exercise level, alcohol
consumption level, smoking status, stress level, and salt intake level). The
study was carried out using a database containing a variety of variables/factors.
Each database of raw data was split into two parts: one part for training the
neural network and the remaining part for testing the performance of the network.
Two neural network algorithms, back-propagation and radial basis function, were
used to construct and validate the prediction system. According to the
experiment, the accuracy of our predictions of systolic blood pressure values
exceeded 90%. Our experimental results show that artificial neural networks are
suitable for modeling and predicting systolic blood pressure. This new method of
predicting systolic blood pressure helps to give an early warning to adults, who
may not get regular blood pressure measurements that their blood pressure might
be at an unhealthy level. Also, because an isolated measurement of blood pressure
is not always very accurate due to daily fluctuations, our predictor can provide
the predicted value as another figure for medical staff to refer to.
PMID- 27496864
TI - Esquirol's change of view towards Pinel's mania without delusion.
AB - We recount how Jean-Etienne Dominique Esquirol (1772-1840) gradually changed his
position towards what Philipe Pinel (1745-1826) referred to as mania without
delusion. Between 1805 and 1838, Esquirol moved from outright rejection,
questioning the very idea of insane persons committing motiveless acts of
violence without delusion, to relative acceptance. He eventually incorporated the
clinical characteristics of mania without delusion in his description of
homicidal monomania, dividing them between reasoning monomania and instinctive
monomania. We examine this change by detailing each of Esquirol's points of
disagreement, which decreased sharply between the completion of his thesis in
1805 and the publication of his chapter on homicidal monomania in 1838.
PMID- 27496865
TI - Progression of EGFR-Mutant Lung Adenocarcinoma is Driven By Alveolar Macrophages.
AB - PURPOSE: Lung adenocarcinomas with mutations in the EGFR have unprecedented
initial responses to targeted therapy against the EGFR. Over time, however, these
tumors invariably develop resistance to these drugs. We set out to investigate
alternative treatment approaches for these tumors. EXPERIMENTAL DESIGN: To
investigate the immunologic underpinnings of EGFR-mutant lung adenocarcinoma, we
utilized a bitransgenic mouse model in which a mutant human EGFR gene is
selectively expressed in the lungs. RESULTS: EGFR oncogene-dependent progression
and remission of lung adenocarcinoma was respectively dependent upon the
expansion and contraction of alveolar macrophages, and the mechanism underlying
macrophage expansion was local proliferation. In tumor-bearing mice, alveolar
macrophages downregulated surface expression of MHC-II and costimulatory
molecules; increased production of CXCL1, CXCL2, IL1 receptor antagonist; and
increased phagocytosis. Depletion of alveolar macrophages in tumor-bearing mice
resulted in reduction of tumor burden, indicating a critical role for these cells
in the development of EGFR-mutant adenocarcinoma. Treatment of mice with EGFR
targeting clinical drugs (erlotinib and cetuximab) resulted in a significant
decrease in alveolar macrophages in these mice. An activated alveolar macrophage
mRNA signature was dominant in human EGFR-mutant lung adenocarcinomas, and the
presence of this alveolar macrophage activation signature was associated with
unfavorable survival among patients undergoing resection for EGFR-mutant lung
adenocarcinoma. CONCLUSIONS: Because of the inevitability of failure of targeted
therapy in EGFR-mutant non-small cell lung cancer (NSCLC), these data suggest
that therapeutic strategies targeting alveolar macrophages in EGFR-mutant NSCLC
have the potential to mitigate progression and survival in this disease. Clin
Cancer Res; 23(3); 778-88. (c)2016 AACR.
PMID- 27496867
TI - Missed Opportunities for HIV Diagnosis.
AB - It has been previously shown that patients may present for multiple health issues
in the years preceding their initial HIV diagnosis. This retrospective cohort
study analyzed the data of patients with a new HIV diagnosis, at Ochsner Health
System between January 1, 2011, and December 31, 2012. The primary end point was
missed opportunities, the number of healthcare visits these patients made in the
2 years prior to being diagnosed with HIV. The 125 patients in the study cohort
had 649 healthcare visits during which an HIV test was not performed. These
missed opportunities are the key to capturing the undiagnosed and unaware HIV
positive individual. Primary care is an ideal setting to conduct HIV testing for
those who have access to regular health care. However, nontraditional providers
should also be encouraged to conduct HIV testing regardless of their ability to
provide treatment because evidence shows that knowledge of the diagnosis may
change behavior.
PMID- 27496866
TI - CD137 Stimulation Enhances Cetuximab-Induced Natural Killer: Dendritic Cell
Priming of Antitumor T-Cell Immunity in Patients with Head and Neck Cancer.
AB - PURPOSE: Cetuximab, an EGFR-specific antibody (mAb), modestly improves clinical
outcome in patients with head and neck cancer (HNC). Cetuximab mediates natural
killer (NK) cell:dendritic cell (DC) cross-talk by cross-linking FcgammaRIIIa,
which is important for inducing antitumor cellular immunity. Cetuximab-activated
NK cells upregulate the costimulatory receptor CD137 (4-1BB), which, when
triggered by agonistic mAb urelumab, might enhance NK-cell functions, to promote
T-cell-based immunity. EXPERIMENTAL DESIGN: CD137 expression on tumor
infiltrating lymphocytes was evaluated in a prospective cetuximab neoadjuvant
trial, and CD137 stimulation was evaluated in a phase Ib trial, in combining
agonistic urelumab with cetuximab. Flow cytometry and cytokine release assays
using NK cells and DC were used in vitro, testing the addition of urelumab to
cetuximab-activated NK, DC, and cross presentation to T cells. RESULTS: CD137
agonist mAb urelumab enhanced cetuximab-activated NK-cell survival, DC
maturation, and tumor antigen cross-presentation. Urelumab boosted DC maturation
markers, CD86 and HLA DR, and antigen-processing machinery (APM) components
TAP1/2, leading to increased tumor antigen cross-presentation. In neoadjuvant
cetuximab-treated patients with HNC, upregulation of CD137 by intratumoral,
cetuximab-activated NK cells correlated with FcgammaRIIIa V/F polymorphism and
predicted clinical response. Moreover, immune biomarker modulation was observed
in an open label, phase Ib clinical trial, of patients with HNC treated with
cetuximab plus urelumab. CONCLUSIONS: These results suggest a beneficial effect
of combination immunotherapy using cetuximab and CD137 agonist in HNC. Clin
Cancer Res; 23(3); 707-16. (c)2016 AACR.
PMID- 27496868
TI - Inositol 1,4,5-trisphosphate-mediated sarcoplasmic reticulum-mitochondrial
crosstalk influences adenosine triphosphate production via mitochondrial Ca2+
uptake through the mitochondrial ryanodine receptor in cardiac myocytes.
AB - AIMS: Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac
myocytes are typically associated with the development of cardiac hypertrophy,
arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3
receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to
determine whether IP3-induced Ca(2+ )release affects mitochondrial function and
determine the underlying mechanisms. METHODS AND RESULTS: We compared the effects
of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation
achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation,
respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP)
generation. Both ET-1 and isoproterenol induced an increase in mitochondrial
Ca(2+ )(Ca(2 +) m) but only ET-1 led to an increase in ATP concentration. ET-1
induced effects were prevented by cell treatment with the IP3 antagonist 2
aminoethoxydiphenyl borate and absent in myocytes from transgenic mice expressing
an IP3 chelating protein (IP3 sponge). Furthermore, ET-1-induced mitochondrial
Ca(2+) uptake was insensitive to the mitochondrial Ca(2+ )uniporter inhibitor
Ru360, however was attenuated by RyRs type 1 inhibitor dantrolene. Using real
time polymerase chain reaction, we detected the presence of all three isoforms of
IP3Rs and RyRs in murine ventricular myocytes with a dominant presence of type 2
isoform for both receptors. CONCLUSIONS: Stimulation of IP3Rs with ET-1 induces
Ca(2+ )release from the SR which is tunnelled to mitochondria via mitochondrial
RyR leading to stimulation of mitochondrial ATP production.
PMID- 27496870
TI - Comparative DNA methylation and gene expression analysis identifies novel genes
for structural congenital heart diseases.
AB - AIMS: For the majority of congenital heart diseases (CHDs), the full complexity
of the causative molecular network, which is driven by genetic, epigenetic, and
environmental factors, is yet to be elucidated. Epigenetic alterations are
suggested to play a pivotal role in modulating the phenotypic expression of CHDs
and their clinical course during life. Candidate approaches implied that DNA
methylation might have a developmental role in CHD and contributes to the long
term progress of non-structural cardiac diseases. The aim of the present study is
to define the postnatal epigenome of two common cardiac malformations,
representing epigenetic memory, and adaption to hemodynamic alterations, which
are jointly relevant for the disease course. METHODS AND RESULTS: We present the
first analysis of genome-wide DNA methylation data obtained from myocardial
biopsies of Tetralogy of Fallot (TOF) and ventricular septal defect patients. We
defined stringent sets of differentially methylated regions between patients and
controls, which are significantly enriched for genomic features like promoters,
exons, and cardiac enhancers. For TOF, we linked DNA methylation with genome-wide
expression data and found a significant overlap for hypermethylated promoters and
down-regulated genes, and vice versa. We validated and replicated the methylation
of selected CpGs and performed functional assays. We identified a hypermethylated
novel developmental CpG island in the promoter of SCO2 and demonstrate its
functional impact. Moreover, we discovered methylation changes co-localized with
novel, differential splicing events among sarcomeric genes as well as
transcription factor binding sites. Finally, we demonstrated the interaction of
differentially methylated and expressed genes in TOF with mutated CHD genes in a
molecular network. CONCLUSION: By interrogating DNA methylation and gene
expression data, we identify two novel mechanism contributing to the phenotypic
expression of CHDs: aberrant methylation of promoter CpG islands and methylation
alterations leading to differential splicing.
PMID- 27496869
TI - Biology of proprotein convertase subtilisin kexin 9: beyond low-density
lipoprotein cholesterol lowering.
AB - Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low
density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function
mutations in PCSK9 gene are associated with hypocholesterolaemia and protection
against cardiovascular disease, identifying PCSK9 inhibition as a valid
therapeutic approach to manage hypercholesterolaemia and related diseases.
Although PCSK9 is expressed mainly in the liver, it is present also in other
tissues and organs with specific functions, raising the question of whether a
pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated
cardiovascular diseases might be helpful or deleterious in non-hepatic tissues.
For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the
brain, where it was proposed to play a role in development, neurocognitive
process, and neuronal apoptosis. A link between PCSK9 and immunity was also
proposed as both sepsis and viral infections are differentially affected in the
presence or absence of PCSK9. Despite the increasing number of observations, the
debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and
as very effective drugs that inhibit PCSK9 have become available to the
clinician, a better understanding of the biological roles of PCSK9 is warranted.
PMID- 27496872
TI - Endothelial Jag1-RBPJ signalling promotes inflammatory leucocyte recruitment and
atherosclerosis.
AB - Aim: To determine the role of NOTCH during the arterial injury response and the
subsequent chronic arterial-wall inflammation underlying atherosclerosis. Methods
and results: We have generated a mouse model of endothelial-specific (Cdh5
driven) depletion of the Notch effector recombination signal binding protein for
immunoglobulin kappa J region (RBPJ) [(ApoE-/-); homozygous RBPJk conditional
mice (RBPJflox/flox); Cadherin 5-CreERT, tamoxifen inducible driver mice (Cdh5
CreERT)]. Endothelial-specific deletion of RBPJ or systemic deletion of Notch1 in
athero-susceptible ApoE-/- mice fed a high-cholesterol diet for 6 weeks resulted
in reduced atherosclerosis in the aortic arch and sinus. Intravital microscopy
revealed decreased leucocyte rolling on the endothelium of ApoE-/-;
RBPJflox/flox; Cdh5-CreERT mice, correlating with a lowered content of leucocytes
and macrophages in the vascular wall. Transcriptome analysis revealed down
regulation of proinflammatory and endothelial activation pathways in
atherosclerotic tissue of RBPJ-mutant mice. During normal Notch activation,
Jagged1 signalling up-regulation in endothelial cells promotes nuclear
translocation of the Notch1 intracellular domain (N1ICD) and its physical
interaction with nuclear factor kappa-light-chain-enhancer of activated B cells
(NF-kappaB). This N1ICD-NF-kappaB interaction is required for reciprocal
transactivation of target genes, including vascular cell adhesion molecule-1.
Conclusions: Notch signalling pathway inactivation decreases leucocyte rolling,
thereby preventing endothelial dysfunction and vascular inflammation. Attenuation
of Notch signalling might provide a treatment strategy for atherosclerosis.
PMID- 27496871
TI - C-type natriuretic peptide and natriuretic peptide receptor B signalling inhibits
cardiac sympathetic neurotransmission and autonomic function.
AB - AIMS: B-type natriuretic peptide (BNP)-natriuretic peptide receptor A (NPR-A)
receptor signalling inhibits cardiac sympathetic neurotransmission, although C
type natriuretic peptide (CNP) is the predominant neuropeptide of the nervous
system with expression in the heart and vasculature. We hypothesized that CNP
acts similarly to BNP, and that transgenic rats (TGRs) with neuron-specific
overexpression of a dominant negative NPR-B receptor would develop heightened
sympathetic drive. METHODS AND RESULTS: Mean arterial pressure and heart rate
(HR) were significantly (P < 0.05) elevated in freely moving TGRs (n = 9)
compared with Sprague Dawley (SD) controls (n = 10). TGR had impaired left
ventricular systolic function and spectral analysis of HR variability suggested a
shift towards sympathoexcitation. Immunohistochemistry demonstrated co-staining
of NPR-B with tyrosine hydroxylase in stellate ganglia neurons. In SD rats, CNP
(250 nM, n = 8) significantly reduced the tachycardia during right stellate
ganglion stimulation (1-7 Hz) in vitro whereas the response to bath-applied
norepinephrine (NE, 1 MUM, n = 6) remained intact. CNP (250 nM, n = 8)
significantly reduced the release of 3H-NE in isolated atria and this was
prevented by the NPR-B antagonist P19 (250 nM, n = 6). The neuronal Ca2+ current
(n = 6) and intracellular Ca2+ transient (n = 9, using fura-2AM) were also
reduced by CNP in isolated stellate neurons. Treatment of the TGR (n = 9) with
the sympatholytic clonidine (125 ug/kg per day) significantly reduced mean
arterial pressure and HR to levels observed in the SD (n = 9). CONCLUSION: C-type
natriuretic peptide reduces cardiac sympathetic neurotransmission via a reduction
in neuronal calcium signalling and NE release through the NPR-B receptor.
Situations impairing CNP-NPR-B signalling lead to hypertension, tachycardia, and
impaired left ventricular systolic function secondary to sympatho-excitation.
PMID- 27496873
TI - A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes
dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling
mechanism.
AB - AIM: Mutations in the RS-domain of RNA-binding motif protein 20 (RBM20) have
recently been identified to segregate with aggressive forms of familial dilated
cardiomyopathy (DCM). Loss of RBM20 in rats results in missplicing of the
sarcomeric gene titin (TTN). The functional and physiological consequences of
RBM20 mutations outside the mutational hotspot of RBM20 have not been explored to
date. In this study, we investigated the pathomechanism of DCM caused by a novel
RBM20 mutation in human cardiomyocytes. METHODS AND RESULTS: We identified a
family with DCM carrying a mutation (RBM20(E913K/+)) in a glutamate-rich region
of RBM20. Western blot analysis of endogenous RBM20 protein revealed strongly
reduced protein levels in the heart of an RBM20(E913K/+ )carrier. RNA deep
sequencing demonstrated massive inclusion of exons coding for the spring region
of titin in the RBM20(E913K/+ )carrier. Titin isoform analysis revealed a
dramatic shift from the less compliant N2B towards the highly compliant N2BA
isoforms in RBM20(E913K/+ )heart. Moreover, an increased sarcomere resting-length
was observed in single cardiomyocytes and isometric force measurements revealed
an attenuated Frank-Starling mechanism (FSM), which was rescued by protein kinase
A treatment. CONCLUSION: A mutation outside the mutational hotspot of RBM20
results in haploinsufficiency of RBM20. This leads to disturbed alternative
splicing of TTN, resulting in a dramatic shift to highly compliant titin isoforms
and an impaired FSM. These effects may contribute to the early onset, and
malignant course of DCM caused by RBM20 mutations. Altogether, our results
demonstrate that heterozygous loss of RBM20 suffices to profoundly impair myocyte
biomechanics by its disturbance of TTN splicing.
PMID- 27496874
TI - Expression of sirtuins 1, 6, tumor necrosis factor, and interferon-gamma in
psoriatic patients.
AB - Sirtuins (SIRT) have been regarded as culprits in the pathogenesis of various
diseases. Their exact role has not been explained. This study aimed to assess the
expression of SIRT1, SIRT6, tumor necrosis factor (TNF)-alpha, and interferon
(IFN)-gamma in psoriatic patients. Thirty psoriatic patients and 22 controls were
enrolled. Clinical examination and Psoriasis Area and Severity Index (PASI) were
obtained. Two skin biopsies (lesional, peri-lesional) and one from controls were
obtained. Tissue levels of SIRT1, SIRT6, TNF-alpha, and IFN-gamma were measured
using ELISA. SIRT1 was significantly lower in lesional skin with gradual increase
in perilesional followed by control skin (P <0.001). SIRT6, TNF-alpha, and IFN
gamma were significantly higher in lesional than perilesional and control skin (P
<0.001). Significant positive correlations were found between SIRT1 and TNF
alpha, IFN-gamma and between SIRT6 and TNF-alpha in peri-lesional skin. SIRT1 and
SIRT6 are potentially involved in the pathogenesis of psoriasis. Modulating their
action could offer a novel therapy for such disease.
PMID- 27496876
TI - Hyperpolarization-activated cyclic nucleotide-gated channels in peripheral
diaphragmatic lymphatics.
AB - Diaphragmatic lymphatic function is mainly sustained by pressure changes in the
tissue and serosal cavities during cardiorespiratory cycles. The most peripheral
diaphragmatic lymphatics are equipped with muscle cells (LMCs), which exhibit
spontaneous contraction, whose molecular machinery is still undetermined.
Hypothesizing that spontaneous contraction might involve hyperpolarization
activated cyclic nucleotide-gated (HCN) channels in lymphatic LMCs, diaphragmatic
specimens, including spontaneously contracting lymphatics, were excised from 33
anesthetized rats, moved to a perfusion chamber containing HEPES-Tyrode's
solution, and treated with HCN channels inhibitors cesium chloride (CsCl),
ivabradine, and ZD-7288. Compared with control, exposure to 10 mM CsCl reduced (
65%, n = 13, P < 0.01) the contraction frequency (FL) and increased end-diastolic
diameter (DL-d, +7.3%, P < 0.01) without changes in end-systolic diameter (DL-s).
Ivabradine (300 MUM) abolished contraction and increased DL-d (-14%, n = 10, P <
0.01) or caused an incomplete inhibition of FL (n = 3, P < 0.01), leaving DL-d
and DL-s unaltered. ZD-7288 (200 MUM) completely (n = 12, P < 0.01) abolished FL,
while DL-d decreased to 90.9 +/- 2.7% of control. HCN gene expression and
immunostaining confirmed the presence of HCN1-4 channel isoforms, likely arranged
in different configurations, in LMCs. Hence, all together, data suggest that HCN
channels might play an important role in affecting contraction frequency of LMCs.
PMID- 27496875
TI - Cardiac-deleterious role of galectin-3 in chronic angiotensin II-induced
hypertension.
AB - Galectin-3 (Gal-3), a member of the beta-galactoside lectin family, has an
important role in immune regulation. In hypertensive rats and heart failure
patients, Gal-3 is considered a marker for an unfavorable prognosis.
Nevertheless, the role and mechanism of Gal-3 action in hypertension-induced
target organ damage are unknown. We hypothesized that, in angiotensin II (ANG II)
induced hypertension, genetic deletion of Gal-3 prevents left ventricular (LV)
adverse remodeling and LV dysfunction by reducing the innate immune responses and
myocardial fibrosis. To induce hypertension, male C57BL/6J and Gal-3 knockout
(KO) mice were infused with ANG II (3 MUg.min-1.kg-1 sc) for 8 wk. We assessed:
1) systolic blood pressure by plethysmography, 2) LV function and remodeling by
echocardiography, 3) myocardial fibrosis by histology, 4) cardiac CD68+
macrophage infiltration by histology, 5) ICAM-1 and VCAM-1 expression by Western
blotting, 6) plasma cytokines, including interleukin-6 (IL-6), by enzyme-linked
immunosorbent assay, and 7) regulatory T (Treg) cells by flow cytometry as
detected by their combined expression of CD4, CD25, and FOXP3. Systolic blood
pressure and cardiac hypertrophy increased similarly in both mouse strains when
infused with ANG II. However, hypertensive C57BL/6J mice suffered impaired
ejection and shortening fractions. In these mice, the extent of myocardial
fibrosis and macrophage infiltration was greater in histological sections, and
cardiac ICAM-1, as well as plasma IL-6, expression was higher as assessed by
Western blotting. However, all these parameters were blunted in Gal-3 KO mice.
Hypertensive Gal-3 KO mice also had a higher number of splenic Treg lymphocytes.
In conclusion, in ANG II-induced hypertension, genetic deletion of Gal-3
prevented LV dysfunction without affecting blood pressure or LV hypertrophy. This
study indicates that the ANG II effects are, in part, mediated or triggered by
Gal-3 together with the related intercellular signaling (ICAM-1 and IL-6),
leading to cardiac inflammation and fibrosis.
PMID- 27496877
TI - Adaptation of the cerebrocortical circulation to carotid artery occlusion
involves blood flow redistribution between cortical regions and is independent of
eNOS.
AB - Cerebral circulation is secured by feed-forward and feed-back control pathways to
maintain and eventually reestablish the optimal oxygen and nutrient supply of
neurons in case of disturbances of the cardiovascular system. Using the high
temporal and spatial resolution of laser-speckle imaging we aimed to analyze the
pattern of cerebrocortical blood flow (CoBF) changes after unilateral (left)
carotid artery occlusion (CAO) in anesthetized mice to evaluate the contribution
of macrovascular (circle of Willis) vs. pial collateral vessels as well as that
of endothelial nitric oxide synthase (eNOS) to the cerebrovascular adaptation to
CAO. In wild-type mice CoBF reduction in the left temporal cortex started
immediately after CAO, reaching its maximum (-26%) at 5-10 s. Thereafter, CoBF
recovered close to the preocclusion level within 30 s indicating the activation
of feed-back pathway(s). Interestingly, the frontoparietal cerebrocortical
regions also showed CoBF reduction in the left (-17-19%) but not in the right
hemisphere, although these brain areas receive their blood supply from the common
azygos anterior cerebral artery in mice. In eNOS-deficient animals the acute CoBF
reduction after CAO was unaltered, and the recovery was even accelerated compared
with controls. These results indicate that 1) the Willis circle alone is not
sufficient to provide an immediate compensation for the loss of one carotid
artery, 2) pial collaterals attenuate the ischemia of the temporal cortex
ipsilateral to CAO at the expense of the blood supply of the frontoparietal
region, and 3) eNOS, surprisingly, does not play an important role in this CoBF
redistribution.
PMID- 27496878
TI - Blood capillary rarefaction and lymphatic capillary neoangiogenesis are key
contributors to renal allograft fibrosis in an ACE inhibition rat model.
AB - Chronic allograft fibrosis is the major cause of graft loss in kidney
transplantation. Progression can only be reduced by inhibition of the renin
angiotensin system (RAS). We tested the hypothesis that the protection provided
by angiotensin-converting enzyme (ACE) inhibition also decreases capillary
rarefaction, lymphangiogenesis, and podocyte injury in allograft fibrosis. Fisher
kidneys were transplanted into bilaterally nephrectomized Lewis rats treated with
enalapril (60 mg/kg per day) (ACE inhibitor, ACEi) or vehicle. Proteinuria, blood
urea nitrogen, and plasma creatinine were regularly assessed, and grafts were
harvested for morphological and immunohistological analysis at various times up
to 32 wk. In the vehicle group, many new lymphatic capillaries and severe and
diffuse mononuclear infiltration of allografts were observed already 1 wk after
transplantation. Lymphangiogenesis increased until week 4, by which time
inflammatory infiltration became focal. Lymphatic capillaries were often located
at sites of inflammation. Progressive interstitial fibrosis, glomerulosclerosis,
capillary rarefaction, and proteinuria appeared later, at weeks 4-12 The number
of lymphatic capillary cross sections strongly correlated with the interstitial
fibrosis score. Podoplanin immunostaining, a marker of healthy podocytes,
disappeared from inflamed or sclerotic glomerular areas. ACEi protected from
lymphangiogenesis and associated inflammation, preserved glomerular podoplanin
protein expression, and reduced glomerulosclerosis, proteinuria,
tubulointerstitial fibrosis, and blood capillary rarefaction at 32 wk. In
conclusion, ACEi considerably decreased and/or delayed both glomerulosclerosis
and tubulointerstitial injury. Prevention of glomerular podoplanin loss and
proteinuria could be attributed to the known intraglomerular pressure-lowering
effects of ACEi. Reduction of lymphangiogenesis could contribute to amelioration
of tubulointerstitial fibrosis and inflammatory infiltration after ACEi.
PMID- 27496879
TI - Endoplasmic reticulum stress increases brain MAPK signaling, inflammation and
renin-angiotensin system activity and sympathetic nerve activity in heart
failure.
AB - We previously reported that endoplasmic reticulum (ER) stress is induced in the
subfornical organ (SFO) and the hypothalamic paraventricular nucleus (PVN) of
heart failure (HF) rats and is reduced by inhibition of mitogen-activated protein
kinase (MAPK) signaling. The present study further examined the relationship
between brain MAPK signaling, ER stress, and sympathetic excitation in HF. Sham
operated (Sham) and HF rats received a 4-wk intracerebroventricular (ICV)
infusion of vehicle (Veh) or the ER stress inhibitor tauroursodeoxycholic acid
(TUDCA, 10 MUg/day). Lower mRNA levels of the ER stress biomarkers GRP78, ATF6,
ATF4, and XBP-1s in the SFO and PVN of TUDCA-treated HF rats validated the
efficacy of the TUDCA dose. The elevated levels of phosphorylated p44/42 and p38
MAPK in SFO and PVN of Veh-treated HF rats, compared with Sham rats, were
significantly reduced in TUDCA-treated HF rats as shown by Western blot and
immunofluorescent staining. Plasma norepinephrine levels were higher in Veh
treated HF rats, compared with Veh-treated Sham rats, and were significantly
lower in the TUDCA-treated HF rats. TUDCA-treated HF rats also had lower mRNA
levels for angiotensin converting enzyme, angiotensin II type 1 receptor, tumor
necrosis factor-alpha, interleukin-1beta, cyclooxygenase-2, and NF-kappaB p65,
and a higher mRNA level of IkappaB-alpha, in the SFO and PVN than Veh-treated HF
rats. These data suggest that ER stress contributes to the augmented sympathetic
activity in HF by inducing MAPK signaling, thereby promoting inflammation and
renin-angiotensin system activity in key cardiovascular regulatory regions of the
brain.
PMID- 27496880
TI - Comprehensive metabolic modeling of multiple 13C-isotopomer data sets to study
metabolism in perfused working hearts.
AB - In many forms of cardiomyopathy, alterations in energy substrate metabolism play
a key role in disease pathogenesis. Stable isotope tracing in rodent heart
perfusion systems can be used to determine cardiac metabolic fluxes, namely those
relative fluxes that contribute to pyruvate, the acetyl-CoA pool, and pyruvate
anaplerosis, which are critical to cardiac homeostasis. Methods have previously
been developed to interrogate these relative fluxes using isotopomer enrichments
of measured metabolites and algebraic equations to determine a predefined
metabolic flux model. However, this approach is exquisitely sensitive to
measurement error, thus precluding accurate relative flux parameter
determination. In this study, we applied a novel mathematical approach to
determine relative cardiac metabolic fluxes using 13C-metabolic flux analysis
(13C-MFA) aided by multiple tracer experiments and integrated data analysis.
Using 13C-MFA, we validated a metabolic network model to explain myocardial
energy substrate metabolism. Four different 13C-labeled substrates were queried
(i.e., glucose, lactate, pyruvate, and oleate) based on a previously published
study. We integrated the analysis of the complete set of isotopomer data gathered
from these mouse heart perfusion experiments into a single comprehensive network
model that delineates substrate contributions to both pyruvate and acetyl-CoA
pools at a greater resolution than that offered by traditional methods using
algebraic equations. To our knowledge, this is the first rigorous application of
13C-MFA to interrogate data from multiple tracer experiments in the perfused
heart. We anticipate that this approach can be used widely to study energy
substrate metabolism in this and other similar biological systems.
PMID- 27496881
TI - Ivabradine and metoprolol differentially affect cardiac glucose metabolism
despite similar heart rate reduction in a mouse model of dyslipidemia.
AB - While heart rate reduction (HRR) is a target for the management of patients with
heart disease, contradictory results were reported using ivabradine, which
selectively inhibits the pacemaker If current, vs. beta-blockers like metoprolol.
This study aimed at testing whether similar HRR with ivabradine vs. metoprolol
differentially modulates cardiac energy substrate metabolism, a factor
determinant for cardiac function, in a mouse model of dyslipidemia (hApoB+/+;LDLR
/-). Following a longitudinal study design, we used 3- and 6-mo-old mice,
untreated or treated for 3 mo with ivabradine or metoprolol. Cardiac function was
evaluated in vivo and ex vivo in working hearts perfused with 13C-labeled
substrates to assess substrate fluxes through energy metabolic pathways. Compared
with 3-mo-old, 6-mo-old dyslipidemic mice had similar cardiac hemodynamics in
vivo but impaired (P < 0.001) contractile function (aortic flow: -45%; cardiac
output: -34%; stroke volume: -35%) and glycolysis (-24%) ex vivo. Despite
inducing a similar 10% HRR, ivabradine-treated hearts displayed significantly
higher stroke volume values and glycolysis vs. their metoprolol-treated
counterparts ex vivo, values for the ivabradine group being often not
significantly different from 3-mo-old mice. Further analyses highlighted
additional significant cardiac alterations with disease progression, namely in
the total tissue level of proteins modified by O-linked N-acetylglucosamine (O
GlcNAc), whose formation is governed by glucose metabolism via the hexosamine
biosynthetic pathway, which showed a similar pattern with ivabradine vs.
metoprolol treatment. Collectively, our results emphasize the implication of
alterations in cardiac glucose metabolism and signaling linked to disease
progression in our mouse model. Despite similar HRR, ivabradine, but not
metoprolol, preserved cardiac function and glucose metabolism during disease
progression.
PMID- 27496888
TI - Imagine a world without borders: an immunologist's thoughts on Brexit.
PMID- 27496882
TI - CXCL16 regulates renal injury and fibrosis in experimental renal artery stenosis.
AB - Recent studies have shown that inflammation plays a critical role in the
initiation and progression of hypertensive kidney disease, including renal artery
stenosis. However, the signaling mechanisms underlying the induction of
inflammation are poorly understood. We found that CXCL16 was induced in the
kidney in a murine model of renal artery stenosis. To determine whether CXCL16 is
involved in renal injury and fibrosis, wild-type and CXCL16 knockout mice were
subjected to renal artery stenosis induced by placing a cuff on the left renal
artery. Wild-type and CXCL16 knockout mice had comparable blood pressure at
baseline. Renal artery stenosis caused an increase in blood pressure that was
similar between wild-type and CXCL16 knockout mice. CXCL16 knockout mice were
protected from RAS-induced renal injury and fibrosis. CXCL16 deficiency
suppressed bone marrow-derived fibroblast accumulation and myofibroblast
formation in the stenotic kidneys, which was associated with less expression of
extracellular matrix proteins. Furthermore, CXCL16 deficiency inhibited
infiltration of F4/80(+) macrophages and CD3(+) T cells in the stenotic kidneys
compared with those of wild-type mice. Taken together, our results indicate that
CXCL16 plays a pivotal role in the pathogenesis of renal artery stenosis-induced
renal injury and fibrosis through regulation of bone marrow-derived fibroblast
accumulation and macrophage and T-cell infiltration.
PMID- 27496890
TI - Laboratory Animals Limited at FELASA Congress, 13-16 June 2016 Brussels, Belgium.
PMID- 27496891
TI - The FELASA Award 2016 - A major award for laboratory animal science within
Europe.
PMID- 27496889
TI - A novel long intergenic noncoding RNA indispensable for the cleavage of mouse two
cell embryos.
AB - Endogenous retroviruses (ERVs) are transcriptionally active in cleavage stage
embryos, yet their functions are unknown. ERV sequences are present in the
majority of long intergenic noncoding RNAs (lincRNAs) in mouse and humans,
playing key roles in many cellular processes and diseases. Here, we identify
LincGET as a nuclear lincRNA that is GLN-, MERVL-, and ERVK-associated and
essential for mouse embryonic development beyond the two-cell stage. LincGET is
expressed in late two- to four-cell mouse embryos. Its depletion leads to
developmental arrest at the late G2 phase of the two-cell stage and to MAPK
signaling pathway inhibition. LincGET forms an RNA-protein complex with hnRNP U,
FUBP1, and ILF2, promoting the cis-regulatory activity of long terminal repeats
(LTRs) in GLN, MERVL, and ERVK (GLKLTRs), and inhibiting RNA alternative
splicing, partially by downregulating hnRNP U, FUBP1, and ILF2 protein levels.
Hnrnpu or Ilf2 mRNA injection at the pronuclear stage also decreases the
preimplantation developmental rate, and Fubp1 mRNA injection at the pronuclear
stage causes a block at the two-cell stage. Thus, as the first functional ERV
associated lincRNA, LincGET provides clues for ERV functions in cleavage stage
embryonic development.
PMID- 27496893
TI - Simposio ORBEA.
PMID- 27496892
TI - SECAL en el Congreso de FELASA (Bruselas).
PMID- 27496895
TI - Identification of genes differentially regulated by vitamin D deficiency that
alter lung pathophysiology and inflammation in allergic airways disease.
AB - Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may
enhance the inflammatory response, and we have previously shown that airway
remodeling and airway hyperresponsiveness is increased in vitamin D-deficient
mice. In this study, we hypothesize that vitamin D deficiency would exacerbate
house dust mite (HDM)-induced inflammation and alterations in lung structure and
function. A BALB/c mouse model of vitamin D deficiency was established by dietary
manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass,
mucus cell metaplasia, lung and airway inflammation, and cytokines in
bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in
mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation
and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance,
and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes
into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against
the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine
genes that were differentially regulated by vitamin D deficiency in the lungs of
HDM-treated mice. Immunohistochemical staining confirmed that protein expression
of midline 1 (MID1) and adrenomedullin was differentially regulated such that
they promoted inflammation, while hypoxia-inducible lipid droplet-associated,
which is associated with ASM remodeling, was downregulated. Protein expression
studies in human bronchial epithelial cells also showed that addition of vitamin
D decreased MID1 expression. Differential regulation of these genes by vitamin D
deficiency could determine lung inflammation and pathophysiology and suggest that
the effect of vitamin D deficiency on HDM-induced allergic airways disease is
complex.
PMID- 27496894
TI - Cadmium attenuates the macrophage response to LPS through inhibition of the NF
kappaB pathway.
AB - Chronic obstructive pulmonary disease (COPD) in the U.S. is primarily caused by
cigarette smoking. COPD patients are highly susceptible to respiratory infections
in part due to alveolar macrophage dysfunction despite a substantial increase in
macrophages in the lung. Cadmium (Cd) is a toxic metal that is concentrated
within tobacco and accumulates in the lung of smokers. We hypothesized that Cd
uptake into macrophages alters immune function thereby impairing the macrophage
response to invading pathogens. Our hypothesis was tested by comparing primary
human monocytes and macrophages, primary mouse bronchoalveolar lavage myeloid
cells, and related cell lines. Strikingly, Cd exposure followed by LPS
stimulation resulted in a dose-dependent, significant decrease in nuclear p65
activity in macrophages that was not observed in monocytes. This corresponded
with Cd-mediated inhibition of IKKbeta and an impaired ability to transcribe and
release cytokines in response to LPS challenge in vivo. These findings provide
novel evidence that Cd has the capacity to disrupt macrophage immune function
compared with monocytes. Importantly, Cd results in immune dysfunction in
macrophages through inhibition of the NF-kappaB signaling pathway. Based on these
findings, we provide new evidence that Cd contributes to immune dysfunction in
the lung of COPD subjects and may increase susceptibility to infection.
PMID- 27496896
TI - Staphylococcus aureus alpha-toxin-mediated cation entry depolarizes membrane
potential and activates p38 MAP kinase in airway epithelial cells.
AB - Membrane potential (Vm)-, Na(+)-, or Ca(2+)-sensitive fluorescent dyes were used
to analyze changes in Vm or intracellular ion concentrations in airway epithelial
cells treated with Staphylococcus aureus alpha-toxin (Hla), a major virulence
factor of pathogenic strains of these bacteria. Gramicidin, a channel-forming
peptide causing membrane permeability to monovalent cations, a mutated form of
Hla, rHla-H35L, which forms oligomers in the plasma membranes of eukaryotic cells
but fails to form functional transmembrane pores, or the cyclodextrin-derivative
IB201, a blocker of the Hla pore, were used to investigate the permeability of
the pore. Na(+) as well as Ca(2+) ions were able to pass the Hla pore and
accumulated in the cytosol. The pore-mediated influx of calcium ions was blocked
by IB201. Treatment of cells with recombinant Hla resulted in plasma membrane
depolarization as well as in increases in the phosphorylation levels of paxillin
(signaling pathway mediating disruption of the actin cytoskeleton) and p38 MAP
kinase (signaling pathway resulting in defensive actions). p38 MAP kinase
phosphorylation, but not paxillin phosphorylation, was elicited by treatment of
cells with gramicidin. Although treatment of cells with rHla-H35L resulted in the
formation of membrane-associated heptamers, none of these cellular effects were
observed in our experiments. This indicates that formation of functional Hla
transmembrane pores is required to induce the cell physiological changes mediated
by alpha-toxin. Specifically, the changes in ion equilibria and plasma membrane
potential are important activators of p38 MAP kinase, a signal transduction
module involved in host cell defense.
PMID- 27496897
TI - CCSP G38A polymorphism environment interactions regulate CCSP levels
differentially in COPD.
AB - Impaired airway homeostasis in chronic obstructive pulmonary disease (COPD) could
be partly related to club cell secretory protein (CCSP) deficiency. We
hypothesize that CCSP G38A polymorphism is involved and aim to examine the
influence of the CCSP G38A polymorphism on CCSP transcription levels and its
regulatory mechanisms. CCSP genotype and CCSP levels in serum and sputum were
assessed in 66 subjects with stable COPD included in a 1-yr observational study.
Forty-nine of them had an exacerbation. In an in vitro study, the impact on the
CCSP promoter of 38G wild-type or 38A variant was assessed. BEAS-2B cells were
transfected by either the 38G or 38A construct, in the presence/absence of
cigarette smoke extract (CSE) or lipopolysaccharides (LPS). Cotransfections with
modulating transcription factors, p53 and Nkx2.1, identified by in silico
analysis by using ConSite and TFSEARCH were conducted. A allele carrier COPD
patients had lower serum and sputum CCSP levels, especially among active smokers,
and a decreased body mass index, airflow obstruction, dyspnea, and exercise
capacity (BODE) score. In vitro, baseline CCSP transcription levels were similar
between the wild and variant constructs. CSE decreased more profoundly the CCSP
transcription level of 38A transfected cells. The opposite effect was observed
with p53 cotransfection. LPS stimulation induced CCSP repression in 38A promoter
transfected cells. Cotransfection with Nkx2.1 significantly activated the CCSP
promoters irrespective of the polymorphism. Circulating CCSP levels are
associated with smoking and the CCSP G38A polymorphism. CSE, LPS, and the Nkx2.1
and p53 transcription factors modulated the CCSP promoter efficiency. The 38A
polymorphism exaggerated the CCSP repression in response to p53 and CSE.
PMID- 27496898
TI - In vitro and in vivo evidence for an inflammatory role of the calcium channel
TRPV4 in lung epithelium: Potential involvement in cystic fibrosis.
AB - Cystic fibrosis (CF) is an inherited disease associated with chronic severe lung
inflammation, leading to premature death. To develop innovative anti-inflammatory
treatments, we need to characterize new cellular and molecular components
contributing to the mechanisms of lung inflammation. Here, we focused on the
potential role of "transient receptor potential vanilloid-4" (TRPV4), a
nonselective calcium channel. We used both in vitro and in vivo approaches to
demonstrate that TRPV4 expressed in airway epithelial cells triggers the
secretion of major proinflammatory mediators such as chemokines and biologically
active lipids, as well as a neutrophil recruitment in lung tissues. We
characterized the contribution of cytosolic phospholipase A2, MAPKs, and NF
kappaB in TRPV4-dependent signaling. We also showed that 5,6-, 8,9-, 11,12-, and
14,15-epoxyeicosatrienoic acids, i.e., four natural lipid-based TRPV4 agonists,
are present in expectorations of CF patients. Also, TRPV4-induced calcium
mobilization and inflammatory responses were enhanced in cystic fibrosis
transmembrane conductance regulator-deficient cellular and animal models,
suggesting that TRPV4 is a promising target for the development of new anti
inflammatory treatments for diseases such as CF.
PMID- 27496899
TI - The transition to clinical expert: enhanced decision making for children aged
less than 5 years attending the paediatric ED with acute respiratory conditions.
AB - BACKGROUND: Rates of unplanned paediatric admissions are persistently high. Many
admissions are short-stay events, lasting less than 48 hours. OBJECTIVE: This
qualitative research explores factors that influence clinical decision making in
the paediatric ED (PED) for children under 5 attending with acute respiratory
conditions, focusing on how management decisions adapt with increasing
experience. METHOD: Semi-structured interviews were conducted with 15 PED
clinicians (doctors, emergency nurse practitioners and registered nurses) with
varying levels of experience in paediatric emergency medicine (PEM), emergency
medicine or paediatrics. Audio-recorded interviews were transcribed and analysed
thematically. RESULTS: There were clear differences in decision-making approaches
between experienced clinicians and junior staff. The latter were more risk
adverse, relying heavily on guidelines, set admission criteria, clinical theory
and second opinions. This was particularly true for doctors. 'Informal' learning
was apparent in accounts from less-experienced doctors and nurses, whereby tacit
knowledge and risk management played an increasing role in the development of
clinical intuition that permitted rapid assessment and treatment of young
patients. CONCLUSIONS: The emergence of intuition entwined with approaches to
risk management and the role of these skills in clinical decision making, carry
implications for the development of training programmes for clinicians working in
PEM. Enhanced training for such groups to permit development of the supplementary
skills described in this study could have the ability to improve care delivery
and even reduce paediatric admissions.
PMID- 27496900
TI - Entheseal involvement in systemic lupus erythematosus: are we missing something?
AB - Background Musculoskeletal involvement is extremely common in patients with
systemic lupus erythematosus (SLE). Continuing the research initiated in patients
with inflammatory arthritis, recent studies have shown the potential role of
musculoskeletal ultrasound (MSUS) in the evaluation of clinical and subclinical
lupus synovitis. The inflammatory process in SLE is traditionally considered to
be localized at synovial tissue areas while enthesis is not included among the
possible targets of the disease. Patients and methods Entheses included in the
Glasgow Ultrasound Enthesitis Scoring System were scanned in a cohort of 20 SLE
patients serving as disease controls in an MSUS study aimed at assessing
enthesitis in patients with psoriatic arthritis. We describe in detail four cases
with unexpected and unequivocal expressions of MSUS enthesitis according to the
OMERACT definition. Three out of four patients had no predisposing factors for
enthesopathy. Case no. 2 was treated with a variable-dose prednisone regimen.
Results In the four cases MSUS examination revealed relevant grey-scale and power
Doppler abnormalities at the entheseal level, most commonly at the distal
insertion of the patellar tendon. Signs of clinical enthesitis were detected in
only one patient. Conclusions This case series shows for the first time the
presence of clearly evident MSUS findings indicative of enthesitis in four out of
20 SLE patients (20%), raising the hypothesis that enthesis could be a missing
target in the clinical evaluation of SLE patients. Our case series justifies
further investigations for a better evaluation of the prevalence, characteristics
and clinical relevance of entheseal involvement in SLE.
PMID- 27496901
TI - Relationship between health-related quality of life, disease activity and disease
damage in a prospective international multicenter cohort of childhood onset
systemic lupus erythematosus patients.
AB - Previously, we described associations between health-related quality of life
(HRQOL) and disease-related factors among childhood onset systemic lupus
erythematosus (cSLE) patients. Here we determined the relationship between HRQOL,
disease activity and damage in a large prospective international cohort of cSLE.
We compared HRQOL, disease activity and disease damage across different
continents and examined the relationship between children's and parents'
assessments of HRQOL. Patients with cSLE and their parents completed HRQOL
measures at enrollment and >=4 follow-up visits. Physicians assessed disease
activity and damage. The multinational cohort ( n = 467) had relatively low
disease activity and damage. Patient and parent HRQOL scores were significantly
correlated. Asian and European patients had the highest HRQOL, while South and
North American patients had lower HRQOL scores. Renal, CNS, skin and
musculoskeletal systems exhibited the highest levels of damage. North and South
American and Asian patients were more likely to have disease damage and activity
scores above median values, compared with Europeans. Asians were more likely to
use cyclophosphamide/rituximab. Female gender, high disease activity and damage,
non-White ethnicity, and use of cyclophosphamide and/rituximab were related to
lower HRQOL. HRQOL domain scores continue to emphasize that SLE has widespread
impact on all aspects of children's and parents' lives.
PMID- 27496902
TI - Response to letter regarding article 'Comparison of myelin water fraction values
in periventricular white matter lesions between multiple sclerosis and
neuromyelitis optica spectrum disorder'.
PMID- 27496903
TI - Comparison of myelin water fraction values in periventricular white matter
lesions between MS and NMOSD.
PMID- 27496904
TI - Biomechanical Evaluation of Glenoid Version and Dislocation Direction on the
Influence of Anterior Shoulder Instability and Development of Hill-Sachs Lesions.
AB - BACKGROUND: Abnormal glenoid version is a risk factor for shoulder instability.
However, the degree to which the variance in version (both anteversion and
retroversion) affects one's predisposition for instability is not well
understood. PURPOSE: To determine the influence of glenoid version on anterior
shoulder joint stability and to determine if the direction of the humeral head
dislocation is a stimulus for the development of Hill-Sachs lesions. STUDY
DESIGN: Controlled laboratory study. METHODS: Ten human cadaveric shoulders (mean
age, 59.4 +/- 4.3 years) were tested using a custom shoulder dislocation device
placed in a position of apprehension (90 degrees of abduction with 90 degrees
of external rotation). Glenoid version was adjusted in 5 degrees increments for
a total of 6 version angles tested: +10 degrees , +5 degrees , 0 degrees , -5
degrees , -10 degrees , and -15 degrees (anteversion angles are positive, and
retroversion angles are negative). Two humeral dislocation directions were
tested. The first direction was true anterior through the anterior-posterior
glenoid axis. The second dislocation direction was 35 degrees inferior from the
anterior-posterior glenoid axis based on the deforming force role of the
pectoralis major. The force and energy to dislocate were recorded. RESULTS:
Changes in glenoid version manifested a linear effect on the dislocation force.
The energy to dislocate increased as a second-order polynomial as a function of
increasing glenoid retroversion. Glenoid version of +10 degrees anteversion and
15 degrees retroversion was highly unstable, resulting in spontaneous
dislocation in one-quarter (10/40) and one-half (25/40) of the specimens
anteriorly and posteriorly, respectively, in the absence of an applied
dislocation force. The greater tuberosity was observed to engage with the
anterior glenoid rim, consistent with Hill-Sachs lesions, 40% more frequently
when the dislocation direction was true anterior compared with 35 degrees
inferior from the anterior-posterior glenoid axis. The engagement of the greater
tuberosity caused an increase in the energy required to dislocate. CONCLUSION:
Glenoid version has a direct effect on the force required for a dislocation. An
anterior-inferior dislocation direction requires less energy for a dislocation
and results in a lower risk of the development of a Hill-Sachs lesion than a
direct anterior dislocation direction. CLINICAL RELEVANCE: Consideration should
be given to glenoid version when choosing a surgical treatment option for
anterior shoulder instability.
PMID- 27496905
TI - Diagnosis of Engaging Bipolar Bone Defects in the Shoulder Using 2-Dimensional
Computed Tomography: A Cadaveric Study.
AB - BACKGROUND: Anatomic studies have demonstrated that bipolar glenoid and humeral
bone loss have a cumulative effect on shoulder instability and that these defects
may engage in functional positions depending on their size and location,
potentially resulting in failure of stabilization procedures. Determining which
lesions pose a risk for engagement remains challenging, with arthroscopic
assessments and a 3-dimensional computed tomography (CT)-based glenoid track
method being accepted approaches at this time. PURPOSE: The purpose was to
investigate the interaction of humeral and glenoid bone defects on shoulder
engagement in a cadaveric model. Two alternative approaches to predicting
engagement were evaluated: (1) CT of the shoulder in abduction and external
rotation (ABER) and (2) measurement of the glenoid lesion width and measurement
of a novel parameter, the intact anterior articular angle (IAAA), on conventional
2-dimensional multiplane reformats. STUDY DESIGN: Controlled laboratory study.
METHODS: Hill-Sachs and glenoid defects of varying sizes were created in 12
cadaveric upper limbs, producing 45 bipolar defect combinations. The defect
characteristics were assessed using CT with the shoulder in a neutral position.
ABER CT was performed with the shoulder positioned in 60 degrees of glenohumeral
abduction (corresponding to 90 degrees of abduction relative to the trunk) and
90 degrees of external rotation. The IAAA was measured as the cartilage arc
angle anterior to the Hill-Sachs defect on the axial slice bisecting the humeral
head. The performance of the ABER CT and IAAA approaches to predicting engagement
were compared with the glenoid track method. RESULTS: Of the 45 defect
combinations, 24 (53%) were classified as engaging using the glenoid track
method. ABER CT predicted engagement accurately in 43 of 45 (96%), with a
sensitivity and specificity of 92% and 100%, respectively. A logistic model based
on the glenoid defect width and IAAA provided a prediction accuracy of 87%, with
a sensitivity and specificity of 92% and 81%, respectively. CONCLUSION/CLINICAL
RELEVANCE: Bipolar lesions at risk for engagement can be identified accurately
using an ABER CT scan or by performing 2-dimensional measurements of the glenoid
defect width and IAAA on conventional CT multiplane reformats. This information
will be useful for surgical planning in the setting of bipolar bone defects
before shoulder stabilization.
PMID- 27496906
TI - Osteochondral Allograft Transplantation in Patients With Osteochondritis
Dissecans of the Knee.
AB - BACKGROUND: Osteochondritis dissecans (OCD) of the knee can be difficult to
treat. Cartilage restoration techniques are often indicated when the lesion or
fragment cannot be salvaged and the patient remains symptomatic. Fresh
osteochondral allograft (OCA) transplantation can restore both bone and cartilage
defects characteristic of OCD. HYPOTHESIS: We hypothesized that osteochondral
allografting is a successful method for treating OCD of the knee. STUDY DESIGN:
Case series; Level of evidence, 4. METHODS: This study comprised 135 patients
(149 knees) who underwent OCA for OCD of the knee (type III or IV) between 1997
and 2013 and had a minimum follow-up of 2 years. The median age was 21 years
(range, 12-55 years) and 75.8% of the patients were male. The mean allograft size
was 7.3 cm2 (range, 2.2-25 cm2). Evaluation included the following: frequency and
type of reoperations; modified Merle d'Aubigne and Postel (18-point) scale;
International Knee Documentation Committee (IKDC) pain, function, and total
scores; and Knee Society function (KS-F) and knee (KS-K) scores. Clinical failure
was defined as revision OCA or conversion to arthroplasty. Graft survivorship was
determined. RESULTS: The median follow-up time was 6.3 years (range, 1.9-16.8
years) and 62% of participants had more than 5-year follow-up. Thirty-four of 149
knees (23%) had reoperations, of which 12 (8%) were classified as allograft
failures (7 OCA revisions, 3 unicompartmental knee arthroplasties, and 2 total
knee arthroplasties). OCA survivorship was 95% at 5 years and 93% at 10 years. Of
the 137 knees whose grafts were still in situ at the latest follow-up, the mean
modified Merle d'Aubigne and Postel (18-point) score was 16.8; IKDC pain,
function, and total scores were 2.1, 8.1, and 82.3; and KS-F and KS-K scores were
95.7 and 94.3, respectively. The majority of patients (95%) reported being
satisfied with the outcome of their procedure. CONCLUSION: OCA transplantation
was an effective treatment for OCD of the knee, with a low rate of graft failure,
significant improvement in pain and function scores, and high patient
satisfaction.
PMID- 27496907
TI - Survivorship and Patient-Reported Outcomes After Comprehensive Arthroscopic
Management of Glenohumeral Osteoarthritis: Minimum 5-Year Follow-up.
AB - BACKGROUND: There are little data on midterm outcomes after the arthroscopic
management of glenohumeral osteoarthritis (GHOA) in young active patients.
PURPOSE: To report outcomes and survivorship for the comprehensive arthroscopic
management (CAM) procedure for the treatment of GHOA at a minimum of 5 years
postoperatively. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The
CAM procedure was performed on a consecutive series of 46 patients (49 shoulders)
with advanced GHOA who met criteria for shoulder arthroplasty but instead opted
for a joint-preserving, arthroscopic surgical option. The procedure included
glenohumeral chondroplasty, capsular release, synovectomy, humeral osteoplasty,
axillary nerve neurolysis, subacromial decompression, loose body removal,
microfracture, and biceps tenodesis. Outcome measures included the American
Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE),
Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), Short Form-12 (SF
12) Physical Component Summary (PCS), visual analog scale for pain, and
satisfaction scores. Kaplan-Meier survivorship analysis was performed with
failure defined as progression to total shoulder arthroplasty (TSA). RESULTS:
Forty-six consecutive patients (49 shoulders) who underwent a CAM procedure at a
minimum of 5 years from surgery were included. Two patients were excluded for
refusing to participate before study initiation. The mean age at surgery was 52
years (range, 27-68 years) in 15 women and 29 men. All patients were recreational
athletes with 7 former collegiate or professional athletes. Twelve shoulders
(26%) progressed to TSA at a mean of 2.6 years (range, 0.5-8.2 years). For
survivorship analysis, the status of the shoulder (preservation of the native
joint or progression to TSA) at a minimum of 5 years was known for 45 of 47 (96%)
shoulders. Survivorship was 95.6% at 1 year, 86.7% at 3 years, and 76.9% at 5
years. For surviving shoulders, minimum 5-year subjective outcome data were
available for 28 of 32 (87.5%) shoulders at a mean of 5.7 years (range, 5-8
years). The mean (+/-SD) ASES score was 84.5 +/- 17, the mean SANE score was 82
+/- 18, the mean QuickDASH score was 15 +/- 13, the mean SF-12 PCS score was 51.0
+/- 9.1, and median patient satisfaction was 9 of a possible 10 points.
CONCLUSION: This study demonstrates significant improvements in midterm clinical
outcomes and high patient satisfaction after the arthroscopic CAM procedure for
GHOA, with a 76.9% survivorship rate at a minimum of 5 years postoperatively. For
patients looking for an alternative to TSA, the CAM procedure can provide
reasonable outcomes and should be considered an effective procedure in
appropriately selected, young active patients. Further studies are warranted to
evaluate long-term outcomes and durability after this procedure.
PMID- 27496908
TI - The Effect of Limited Perioperative Nonsteroidal Anti-inflammatory Drugs on
Patients Undergoing Anterior Cruciate Ligament Reconstruction.
AB - BACKGROUND: The administration of nonsteroidal anti-inflammatory drugs (NSAIDs)
to patients undergoing anterior cruciate ligament reconstruction (ACLR) is
controversial because it may impair tissue healing and clinical outcomes.
PURPOSE: To assess the effect of NSAID administration on patients undergoing
ACLR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included
patients were aged >15 years and were registered in the Norwegian Knee Ligament
Registry from 2008 until 2013 after the primary ACLR. Patients with insufficient
data regarding administration of NSAIDs and those with associated knee ligament
injuries requiring surgical treatment were excluded from this study. Graft
survival was estimated using Kaplan-Meier survival curves, and hazard ratios
(HRs) for revision were evaluated using Cox regression analysis. Logistic
regression analysis was used to calculate the odds ratio (OR) for a Knee Injury
and Osteoarthritis Outcome Score (KOOS)-quality of life (QOL) subscale score <44
at 2-year follow-up. RESULTS: A total of 7822 patients were included in the
analysis for graft survival and assessment for risk of revision. Of these, 4144
patients were administered NSAIDs postoperatively. The mean duration of follow-up
was 2.8 years (range, 0-5.9 years). Administration of NSAIDs did not influence
graft survival (P = .568). Adjusted Cox regression analyses demonstrated the same
finding regarding risk of revision (HR, 1.0; 95% CI, 0.8-1.3). ACLR using a bone
patellar tendon-bone autograft showed a reduced risk of revision (HR, 0.3; 95%
CI, 0.1-0.8) among patients administered NSAIDs. In subgroup analyses of 3144
patients, administration of NSAIDs demonstrated a beneficial effect on the risk
of a KOOS-QOL score <44 at 2-year follow-up (OR, 0.8; 95% CI, 0.6-0.9).
CONCLUSION: Administration of NSAIDs to patients after ACLR does not have a
negative effect on graft survival, risk of revision, or risk of a KOOS-QOL score
<44 at 2-year follow-up. We emphasize using caution when administering NSAIDs by
keeping the duration and dosage of NSAIDs as short and low as possible to ensure
sufficient pain relief while limiting unwanted exposure to any known and unknown
adverse effects of these drugs.
PMID- 27496909
TI - Modified Brostrom Procedure for Chronic Lateral Ankle Instability in Patients
With Generalized Joint Laxity.
AB - BACKGROUND: Generalized joint laxity (GJL) has been considered a risk factor for
late failure of ligament reconstruction in the knee; however, it is not known
whether GJL is the cause of recurrent instability after the modified Brostrom
procedure for chronic lateral ankle instability. PURPOSE: To compare the clinical
results of the modified Brostrom procedure for chronic lateral ankle instability
in patients with or without GJL. STUDY DESIGN: Cohort study; Level of evidence,
3. METHODS: A total of 100 patients (100 ankles) who underwent the modified
Brostrom procedure were divided into 2 groups, with or without GJL, according to
the Beighton criteria. Age and body mass index were matched between the 2 groups.
The mean follow-up duration was 43.3 months in the laxity group (44 ankles;
Beighton score >=5) and 42.9 months in the nonlaxity group (56 ankles). RESULTS:
The mean preoperative Karlsson and American Orthopaedic Foot and Ankle Society
(AOFAS) scores were a respective 53.2 and 60.9 in the laxity group and 53.9 and
62.6 in the nonlaxity group, and these scores improved to 87.4 and 89.5,
respectively, in the laxity group and to 94.1 and 94.8, respectively, in the
nonlaxity group at final follow-up. The mean preoperative talar tilt angle and
anterior talar translation were a respective 12.5 degrees and 8.8 mm in the
laxity group and 10.8 degrees and 8.5 mm in the nonlaxity group, and these
values improved to 7.3 degrees and 6.0 mm, respectively, in the laxity group and
to 5.2 degrees and 5.0 mm, respectively, in the nonlaxity group at final follow
up. Failure rates were 11.4% (5 patients) in the laxity group and 1.8% (1
patient) in the nonlaxity group. Significant differences were found between the 2
groups in terms of the Karlsson score, AOFAS score, talar tilt angle, anterior
talar translation, and failure rate at final follow-up (P < .05). CONCLUSION:
Patients with GJL showed inferior outcomes and a higher failure rate compared
with patients without GJL. Therefore, GJL appears to be a risk factor associated
with recurrent instability after the modified Brostrom procedure.
PMID- 27496910
TI - Comparison of Lateral Closing-Wedge Versus Medial Opening-Wedge High Tibial
Osteotomy on Knee Joint Alignment and Kinematics in the ACL-Deficient Knee.
AB - BACKGROUND: Lateral closing-wedge (LCW) and medial opening-wedge (MOW) high
tibial osteotomies (HTOs) correct varus knee alignment and stabilize the anterior
cruciate ligament (ACL)-deficient knee. Tibiofemoral and patellofemoral alignment
and kinematics after HTO are not well quantified. PURPOSE: To compare the effect
of LCW and MOW HTO on tibiofemoral and patellofemoral alignment in the ACL
deficient knee. STUDY DESIGN: Controlled laboratory study. METHODS: Anterior
drawer, Lachman, and pivot-shift tests were performed on cadaveric specimens (N =
16), and anterior tibial translation and tibial rotation were measured for the
native and ACL-sectioned knee. The right and left knee of each cadaveric specimen
underwent an LCW and MOW HTO, respectively, and stability testing was repeated.
All cadavers underwent pre- and postosteotomy computerized tomography with 3
dimensional computer modeling to determine the effect of HTO on posterior tibial
slope, as well as tibial and patellofemoral axial plane alignment (tibial axial
rotation and patellar axial tilt). RESULTS: Correction to neutral coronal
alignment was obtained with both osteotomy techniques; however, larger posterior
tibial slope neutralization was achieved with LCW compared with MOW (mean +/- SD,
11 degrees +/- 3.8 degrees vs 5 degrees +/- 5 degrees ). LCW demonstrated a
greater decrease in anterior tibial translation (P < .05) during Lachman testing,
with translation values approximating those of the native knee, especially for
the lateral compartment. A similar decrease in anterior tibial translation with
LCW was not found during anterior drawer testing. Anterior tibial translation did
not improve for either the Lachman or the anterior drawer test after MOW.
Osteotomy type did not affect tibial rotation with pivot shift. Relative to MOW,
LCW resulted in greater tibial axial rotation and patellar axial tilt (7.7
degrees +/- 4 degrees and 5.6 degrees +/- 3.9 degrees [LCW], 2.8 degrees +/-
2.3 degrees and 2.4 degrees +/- 0.9 degrees [MOW], respectively; P < .05).
CONCLUSION/CLINICAL RELEVANCE: LCW shows more reproducible posterior tibial slope
neutralization and decreased anterior tibial translation in ACL deficiency
compared with MOW; however, LCW is associated with increased external tibial
axial rotation and lateral patellar tilt, which may adversely affect the
patellofemoral joint. More work is needed to understand the clinical and
functional outcome of these biomechanical findings in the ACL-deficient knee.
PMID- 27496911
TI - Recent developments in the detection and management of acute kidney injury.
AB - Acute kidney injury (AKI) is a common condition in children admitted to hospital
and existing serum and urine biomarkers are insensitive. There have been
significant developments in stratifying the risk of AKI in children and also in
the identification of new AKI biomarkers. Risk stratification coupled with a
panel of AKI biomarkers will improve future detection of AKI, however, paediatric
validation studies in mixed patient cohorts are required. The principles of
effective management rely on treating the underlying cause and preventing
secondary AKI by the appropriate use of fluids and medication. Further
therapeutic innovation will depend on improving our understanding of the basic
mechanisms underlying AKI in children.
PMID- 27496912
TI - Simultaneous detection and estimation of trait associations with genomic
phenotypes.
AB - Genomic phenotypes, such as DNA methylation and chromatin accessibility, can be
used to characterize the transcriptional and regulatory activity of DNA within a
cell. Recent technological advances have made it possible to measure such
phenotypes very densely. This density often results in spatial structure, in the
sense that measurements at nearby sites are very similar. In this article, we
consider the task of comparing genomic phenotypes across experimental conditions,
cell types, or disease subgroups. We propose a new method, Joint Adaptive
Differential Estimation (JADE), which leverages the spatial structure inherent to
genomic phenotypes. JADE simultaneously estimates smooth underlying group average
genomic phenotype profiles and detects regions in which the average profile
differs between groups. We evaluate JADE's performance in several biologically
plausible simulation settings. We also consider an application to the detection
of regions with differential methylation between mature skeletal muscle cells,
myotubes, and myoblasts.
PMID- 27496914
TI - Large-diameter total hip arthroplasty modular heads require greater assembly
forces for initial stability.
AB - OBJECTIVES: Modular junctions are ubiquitous in contemporary hip arthroplasty.
The head-trunnion junction is implicated in the failure of large diameter metal
on-metal (MoM) hips which are the currently the topic of one the largest legal
actions in the history of orthopaedics (estimated costs are stated to exceed $4
billion). Several factors are known to influence the strength of these press-fit
modular connections. However, the influence of different head sizes has not
previously been investigated. The aim of the study was to establish whether the
choice of head size influences the initial strength of the trunnion-head
connection. MATERIALS AND METHODS: Ti-6Al-4V trunnions (n = 60) and two different
sizes of cobalt-chromium (Co-Cr) heads (28 mm and 36 mm; 30 of each size) were
used in the study. Three different levels of assembly force were considered: 4
kN; 5 kN; and 6 kN (n = 10 each). The strength of the press-fit connection was
subsequently evaluated by measuring the pull-off force required to break the
connection. The statistical differences in pull-off force were examined using a
Kruskal-Wallis test and two-sample Mann-Whitney U test. Finite element and
analytical models were developed to understand the reasons for the experimentally
observed differences. RESULTS: 36 mm diameter heads had significantly lower pull
off forces than 28 mm heads when impacted at 4 kN and 5 kN (p < 0.001; p <
0.001), but not at 6 kN (p = 0.21). Mean pull-off forces at 4 kN and 5 kN
impaction forces were approximately 20% larger for 28 mm heads compared with 36
mm heads. Finite element and analytical models demonstrate that the differences
in pull-off strength can be explained by differences in structural rigidity and
the resulting interface pressures. CONCLUSION: This is the first study to show
that 36 mm Co-Cr heads have up to 20% lower pull-off connection strength compared
with 28 mm heads for equivalent assembly forces. This effect is likely to play a
role in the high failure rates of large diameter MoM hips.Cite this article: A.
R. MacLeod, N. P. T. Sullivan, M. R. Whitehouse, H. S. Gill. Large-diameter total
hip arthroplasty modular heads require greater assembly forces for initial
stability. Bone Joint Res 2016;5:338-346. DOI: 10.1302/2046-3758.58.BJR-2016
0044.R1.
PMID- 27496913
TI - Incisional negative pressure wound therapy dressings (iNPWTd) in routine primary
hip and knee arthroplasties: A randomised controlled trial.
AB - OBJECTIVES: Wound complications are reported in up to 10% hip and knee
arthroplasties and there is a proven association between wound complications and
deep prosthetic infections. In this randomised controlled trial (RCT) we explore
the potential benefits of a portable, single use, incisional negative pressure
wound therapy dressing (iNPWTd) on wound exudate, length of stay (LOS), wound
complications, dressing changes and cost-effectiveness following total hip and
knee arthroplasties. METHODS: A total of 220 patients undergoing elective primary
total hip and knee arthroplasties were recruited into in a non-blinded RCT. For
the final analysis there were 102 patients in the study group and 107 in the
control group. RESULTS: An improvement was seen in the study (iNPWTd) group
compared to control in all areas. Peak post-surgical wound exudate was
significantly reduced (p = 0.007). Overall LOS reduction (0.9 days, 95%
confidence interval (CI) -0.2 to 2.5) was not significant (p = 0.07) but there
was a significant reduction in patients with extreme values of LOS in the iNPWTd
group (Moses test, p = 0.003). There was a significantly reduced number of
dressing changes (mean difference 1.7, 95% CI 0.8 to 2.5, p = 0.002), and a trend
to a significant four-fold reduction in reported post-operative surgical wound
complications (8.4% control; 2.0% iNPWTd, p = 0.06). CONCLUSIONS: Based on the
results of this RCT incisional negative pressure wound therapy dressings have a
beneficial role in patients undergoing primary hip and knee arthroplasty to
achieve predictable length of stay, especially to eliminate excessive hospital
stay, and minimise wound complications.Cite this article: S. L. Karlakki, A. K.
Hamad, C. Whittall, N. M. Graham, R. D. Banerjee, J. H. Kuiper. Incisional
negative pressure wound therapy dressings (iNPWTd) in routine primary hip and
knee arthroplasties: A randomised controlled trial. Bone Joint Res 2016;5:328
337. DOI: 10.1302/2046-3758.58.BJR-2016-0022.R1.
PMID- 27496915
TI - Prevalence and associated factors of elder mistreatment: a cross sectional study
from urban Nepal.
AB - BACKGROUND: mistreatment of elderly people is internationally recognised as a
serious public health issue. This study aimed at estimating the prevalence and
risk factors associated with mistreatment in urban Nepal. METHODS: this was a
descriptive cross-sectional study of 212 elderly people residing in Butwal sub
metropolitan city, an urban area in Nepal; the study was conducted between March
and October 2015. Two-stage cluster design with simple random sampling was
adopted for the study. Information was collected using an interviewer
administered semi-structured questionnaire of older people. Logistic regression
analysis was used to identify factors associated with elder mistreatment.
RESULTS: this study found a prevalence of 49.1% for mistreatment of the elderly
population. Prevalence rates of caregiver neglect, financial, psychological or
physical mistreatment and other types (including sexual assault) were 47.2%,
11.8%, 10.8%, 1.42% and 3.3%, respectively. Being a dalit (untouchable backward
class in the traditional Hindu caste system), unemployed, widowed, divorced or
separated, problems concentrating and smoking were independent factors associated
with mistreatment. Smoking was found to be consistently associated with the three
most common mistreatment types. CONCLUSIONS: mistreatment of older people is
common in urban Nepal, with neglect, financial and psychological abuse most
common. Along with standard risk factors, specific ethnic issues (membership of
dalit community) are associated with increased risk.
PMID- 27496916
TI - Diurnal and seasonal patterns in presentations with hip fracture-data from the
national hip fracture database.
AB - PURPOSE: we set out to examine diurnal and seasonal variation in hip fracture
presentations to question their origin and to consider their implications for the
organisation of health services for older people. METHODS: we used the National
Hip Fracture Database to identify the time of presentation and surgery for 64,102
patients; all those older than 60 years who sustained this injury in England,
Wales and Northern Ireland during 2014. RESULTS: we found marked diurnal
variation in rates of presentation, increasing sharply after 0800 hours and
decreasing only after 1800 hours. Among people who sustained their hip fracture
in hospital (n = 2,761) or in a care home (n = 12,141), there were peaks in
presentations around 0900 and 1800 hours. Time of presentation had a very marked
effect on whether surgery was delayed by more than 24 hours but less against the
national guidelines of surgery within 36 hours or by the next day. There were
15.6% more presentations during December compared to all other months (9.5%
versus 8.2%, P < 0.001), a pattern also found among people living in care homes
(9.1% versus 8.3%, P < 0.001). CONCLUSIONS: we have identified morning and
evening peaks of presentation for inpatients and care home residents and a
December increase in overall hip fracture numbers. These patterns warrant further
investigation if those organising health services are to prevent this injury, and
to provide appropriate beds and prompt operations for the people who sustain it.
PMID- 27496917
TI - New horizons: urgent care for older people with frailty.
AB - Urgent care for older people is a major public health issue and attracts much
policy attention. Despite many efforts to curb demand, many older people with
frailty and urgent care needs to access acute hospital services. The predominant
model of care delivered in acute hospitals tends to be medically focussed, yet
the evidence-based approaches that appear to be effective invoke a holistic model
of care, delivered by interdisciplinary teams embedding geriatric competencies
into their service. This article reviews the role for holistic care-termed
Comprehensive Geriatric Assessment in the research literature-and how it can be
used as an organising framework to guide future iterations of acute services to
be better able to meet the multifaceted needs of older people.
PMID- 27496921
TI - Effects of WiiActive exercises on fear of falling and functional outcomes in
community-dwelling older adults: a randomised control trial.
AB - BACKGROUND: the study compares the effects of a Nintendo Wii exercise programme
and a standard Gym-based exercise intervention on fear of falling, knee strength,
physical function and falls rate in older adults. METHODS: eighty community
dwelling adults aged 60 years and above with short physical performance battery
score of 5-9 points and modified falls efficacy scale (MFES) score of <=9 points
participated in the parallel-group randomised trial. Each intervention arm
involved an hour of intervention per week, totalling 12 sessions over 12 weeks.
Besides 1-year fall incidence, the participants were evaluated on MFES, knee
extensor strength (KES), timed-up-and-go test, gait speed, 6-minute walk test and
narrow corridor walk test at weeks 13 and 24. RESULTS: at week 13, between
interventions, the effect of MFES changes did not reach statistical significance
(difference = -0.07 point, 95% CI -0.56 to 0.42, P = 0.78); at week 24, the Wii
group showed statistically significant effects over the Gym group (difference =
0.8 point, 95% CI 0.27 to 1.29, P < 0.01). For KES, the two groups did not differ
statistically at week 13 (difference = -2.0%, 95% CI -5.6 to -1.7, P = 0.29); at
week 24, the Gym group had greater strength gains than the Wii group (difference
= -5.1%, 95% CI -8.7 to -1.5, P < 0.01). No between-group differences were
observed for other outcome measures. CONCLUSION: on completion of a 12-week
Nintendo Wii exercise programme, there was no significant benefit seen on fear of
falling when compared to a standard Gym-based exercise intervention; however,
post-intervention there was an apparent reduction in fear of falling in the group
allocated to Wii training, despite knee strength apparently improving more in
those allocated to the Gym. It is possible that long-term gains after using the
Wii might be due to a carry-over effect. TRIAL REGISTRATION: Australian New
Zealand Clinical Trials Registry, ACTRN12610000576022.
PMID- 27496922
TI - Association of socioeconomic status and cognitive functioning change among
elderly Chinese people.
AB - BACKGROUND AND OBJECTIVE: the inverse association between high socioeconomic
status and impaired cognitive functioning in old age has been widely studied.
However, it is still inconclusive whether higher socioeconomic status slows the
rate of cognitive decline over ageing, especially in non-Western populations. We
examined this association using a large population-based longitudinal survey of
older Chinese persons. METHODS: the sample came from the Chinese Longitudinal
Healthy Longevity Survey (CLHLS) (from the years 2002 to 2011, N = 15,798 at
baseline, aged 65-105). The Mini-Mental State Examination (MMSE) based on face-to
face interviews was used to assess cognitive functioning. Socioeconomic status
was assessed using educational attainment and household income per capita. Latent
growth curve and selection model considering the attrition during the follow-up
were utilised to assess the effect of socioeconomic status on the rate of change
in cognitive functioning. RESULTS: at baseline, younger elderly people, urban
residents and elderly people living alone had better cognitive performance in
both genders. Educational attainment was positively associated with cognitive
functioning at baseline but did not have a significant effect on the rate of
change in cognitive functioning. Higher incomes were associated with better
cognitive functioning at baseline, but this difference diminished during the
follow-up. CONCLUSION: higher socioeconomic status was associated with better
cognitive performance at baseline but could not protect against the rate of
decline in cognitive functioning measured by MMSE in this longitudinal study for
elderly Chinese people.
PMID- 27496923
TI - Blood pressure and all-cause mortality: a prospective study of nursing home
residents.
AB - AIM: to explore the natural course of blood pressure development and its relation
to mortality in a nursing home cohort. METHODS: a cohort of 406 nursing home
residents in south east Sweden was followed prospectively for 30 months.
Participants were divided into four groups based on systolic blood pressure (SBP)
at baseline. Data were analysed using a Cox regression model with all-cause
mortality as the outcome measurement; paired Student t-tests were used to
evaluate blood pressure development over time. RESULTS: during follow-up, 174
(43%) people died. Participants with SBP < 120 mmHg had a hazard ratio for
mortality of 1.56 (95% confidence interval, 1.08-2.27) compared with those with
SBP 120-139 mmHg, adjusted for age and sex. Risk of malnutrition or present
malnutrition was most common in participants with SBP < 120 mmHg; risk of
malnutrition or present malnutrition estimated using the Mini Nutritional
Assessment was found in 78 (71%). The levels of SBP decreased over time
independent of changes in anti-hypertensive medication. CONCLUSIONS: in this
cohort of nursing home residents, low SBP was associated with increased all-cause
mortality. SBP decreased over time; this was not associated with altered anti
hypertensive treatment. The clinical implication from this study is that there is
a need for systematic drug reviews in elderly persons in nursing homes, paying
special attention to those with low SBP.
PMID- 27496924
TI - Age- and sex-related differences in use of guideline-recommended care and
mortality among patients with incident heart failure in Denmark.
AB - BACKGROUND: data are sparse on age- and sex-related differences in use of
guideline-recommended care and subsequent mortality among patients with heart
failure (HF). METHODS: we identified 24,308 incident patients with a verified
primary diagnosis of HF recorded during 2003-2010 in the Danish Heart Failure
Registry. The registry monitors guideline-recommended processes of care:
echocardiography, New York Heart Association Classification, treatment with
angiotensin converting enzyme inhibitors/angiotensin II receptor blockers,
betablockers, physical training and patient education. RESULTS: older age was
associated with lower use of recommended processes of care. Relative risk (RR)
for receiving processes of care varied for men >80 years from 0.52 to 0.91
compared with men <=65 years. Corresponding RRs among women >80 years varied from
0.55 to 0.89 compared with women <=65 years. Older age was as expected associated
with higher 1 year mortality (32.6% among men >80 years versus 5.4% among men
<=65 years and 33.8% among women >80 years versus 6.6% among women <=65 years).
The corresponding hazard ratios (HRs) were 4.54 (95% CI 3.93-5.25) and 4.08 (95%
CI 3.51-4.75) for the oldest versus youngest men and women, after adjustment for
patient characteristics. Adjustment for differences in care lowered HRs among the
oldest age groups (adjusted HR 3.87 for men and 3.48 for women, respectively).
The findings were also confirmed when stratifying the patients according to left
ventricular ejection fraction <=40% and >40%. CONCLUSION: older patients with HF
were less likely to receive guideline-recommended processes of care, irrespective
of sex. Lower level of care may contribute to an excess mortality observed among
the older patients.
PMID- 27496925
TI - Calibrating EASY-Care independence scale to improve accuracy.
AB - BACKGROUND: there is currently limited support for the reliability and validity
of the EASY-Care independence scale, with little work carried out in low- or
middle-income countries. Therefore, we assessed the internal construct validity
and hierarchical and classical scaling properties among frail dependent older
people in the community. OBJECTIVE: we assessed the internal construct validity
and hierarchical and classical scaling properties among frail dependent older
people in the community. METHODS: three primary care physicians administered EASY
Care comprehensive geriatric assessment for 150 frail and/or dependent older
people in the primary care setting. A Mokken model was applied to investigate
hierarchical scaling properties of EASY-Care independence scale, and internal
consistency (Cronbach's alpha) of the scale was also examined. RESULTS: we found
that EASY-Care independence scale is highly internally consistent and is a strong
hierarchical scale, hence providing strong evidence for unidimensionality.
However, two items in the scale (unable to use telephone and manage finances) had
much lower item Loevinger H coefficients than others. Exclusion of these two
items improved the overall internal consistency of the scale. CONCLUSIONS: the
strong performance of the EASY-Care independence scale among community-dwelling
frail older people is encouraging. This study confirms that EASY-Care
independence scale is highly internally consistent and a strong hierarchical
scale.
PMID- 27496926
TI - Corrigendum: Corrigendum to 'Tenacious goal pursuit and flexible goal adjustment
in older people over 5 years: a latent profile transition analysis'.
PMID- 27496927
TI - Older people's experiences and perspectives of elder abuse: what next?
PMID- 27496928
TI - Smallest worthwhile effect of exercise programs to prevent falls among older
people: estimates from benefit-harm trade-off and discrete choice methods.
AB - BACKGROUND: the smallest worthwhile effect (SWE) of an intervention is the
smallest treatment effect that justifies the costs, risks and inconveniences
associated with that health intervention. OBJECTIVE: to estimate the SWE of
exercise programs designed to prevent falls among older people and to compare
estimates derived by two methodological approaches. STUDY DESIGN AND SETTING:
discrete choice experiment (n = 220) and benefit-harm trade-off (subsample n =
66) methods were used. PARTICIPANTS: community-dwelling older people who reported
a past fall or a mobility limitation answered online or face-to-face
questionnaires. RESULTS: a substantial proportion of participants (82% in the
discrete choice experiment and 50% in the benefit-harm trade-off study) did not
consider that participation in the proposed exercise programs would be
worthwhile, even if it reduced their risk of falling to 0%. Among remaining
participants, the average SWE of participation in an exercise program was an
absolute reduction in the risk of falling of 35% (standard deviation [SD] = 13)
in the discrete choice experiment and 16% (SD = 11) in the benefit-harm trade-off
study. CONCLUSIONS: many participants did not consider the hypothetical falls'
risk reduction of the proposed exercise programs to be worth the associated costs
and inconveniences. Greater community awareness of the fall prevention effects of
exercise for older people is required.
PMID- 27496929
TI - Centenarian athletes: Examples of ultimate human performance?
AB - BACKGROUND: some centenarians are engaged in regular physical activity and
sometimes in sporting events. OBJECTIVE: we aimed to identify world records of
centenarian athletes in several sports and determine which represented the best
performance when compared to all-age world records, all disciplines taken
together. METHODS: all of the best performances achieved by centenarians were
identified and compared in three disciplines: athletics, swimming and cycling.
The performances were considered as an average of the respective speeds, except
for jumping and throwing events for which the maximum distances performed were
considered. Within each discipline, the decline in performance of centenarian
athletes was expressed as a percentage of the world record for that discipline.
In total, 60 performances of centenarian athletes were found. These performances
belong to 19 individuals: 10 in athletics, 8 in swimming and 1 in cycling.
RESULTS: the centenarian world record performed by Robert Marchand in one hour
track cycling appears to be the best performance (-50.6% compared with the all
age world record in this discipline) achieved by a centenarian. CONCLUSIONS:
although the physiological characteristics of Robert Marchand are certainly
exceptional, his remarkable performance could also be due to the lower age
related decline for cycling performances compared with running and swimming. Our
observations offer new perspectives on how the human body can resist the
deleterious effects of ageing.
PMID- 27496930
TI - STOPP/START version 2-development of software applications: easier said than
done?
AB - Explicit criteria, such as the STOPP/START criteria, are increasingly used both
in clinical practice and in research to identify potentially inappropriate
prescribing in older people. In an article on the STOPP/START criteria version 2,
O'Mahony et al have pointed out the advantages of developing computerised
criteria. Both clinical decision support systems to support healthcare
professionals and software applications to automatically detect inappropriate
prescribing in research studies can be developed. In the process of developing
such tools, difficulties may occur. In the context of a research study, we have
developed an algorithm to automatically apply STOPP/START criteria version 2 to
our research database. We comment in this paper on different kinds of
difficulties encountered and make suggestions that could be taken into account
when developing the next version of the criteria.
PMID- 27496931
TI - C-reactive protein level partially mediates the relationship between moderate
alcohol use and frailty: the Health and Retirement Study.
AB - BACKGROUND: frailty is an indicator of late-life decline marked by higher rates
of disability and healthcare utilisation. Research has linked health benefits
with moderate alcohol use, including frailty risk reduction. Past work suggests
inflammation, measured by C-reactive protein (CRP), as one candidate mechanism
for this effect. OBJECTIVE: this study aims to elucidate a possible mechanism -
CRP modulation - by which moderate alcohol consumption may protect against
frailty. METHODS: a cross-sectional study using data from the 2008 wave of the
Health and Retirement Study (HRS) conducted by the University of Michigan. The
HRS is a cohort study on health, retirement and aging on adults aged 50 and older
living in the USA. A final sample of 3,229 stroke-free participants, over the age
of 65 years and with complete data, was identified from the 2008 wave. Alcohol
use was measured via self-report. Frailty was measured using the Paulson
Lichtenberg Frailty Index. CRP was collected through the HRS protocol. RESULTS:
results from structural equation modelling support the hypothesised model that
moderate alcohol use is associated with less frailty and lower CRP levels.
Furthermore, the indirect relationship from moderate alcohol use to frailty
through CRP was statistically significant. CONCLUSIONS: overall findings suggest
that inflammation measured by CRP is one mechanism by which moderate alcohol use
may confer protective effects for frailty. These findings inform future research
relating alcohol use and frailty, and suggest inflammation as a possible
mechanism in the relationship between moderate alcohol use and other beneficial
health outcomes.
PMID- 27496932
TI - Digit Symbol Substitution test and future clinical and subclinical disorders of
cognition, mobility and mood in older adults.
AB - OBJECTIVE: to examine whether psychomotor speed predicts individual and combined
disorders in cognition, mobility and mood and if white matter hyperintensities
explain these associations. DESIGN AND SETTING: longitudinal; Cardiovascular
Health Study. SUBJECTS: 5,888 participants (57.6% women, 15.7% black, 75.1 (5.5),
mean years (SD)). METHODS: psychomotor speed (Digit Symbol Substitution Test
(DSST)) and small vessel disease (white matter hyperintensities (WMH)) were
measured in 1992-94. Global cognition (Modified Mini-Mental State (3MS)
examination), mobility (gait speed (GS)) and mood (Center for Epidemiologic
Studies Depression (CES-D) scale) were measured annually over 5 years and
classified as clinical, subclinical or no disorders based on established values
(3MS: 80 and 85 points; GS: 0.6 and 1.0 m/s; CES-D: 10 and 5 points). Analyses
were adjusted for demographics, baseline status, education, diabetes,
hypertension, ankle-arm index. RESULTS: among those with no disorder in
cognition, mobility and mood (N = 619) in 1992-94, being in the lowest DSST
quartile compared to the highest was associated with nearly twice the odds of
developing 1+ clinical or subclinical disorders (N = 413) during follow-up.
Associations were stronger for incident clinical disorders in cognition (OR:
8.44, p < 0.01) or mobility (OR: 9.09, p < 0.05) than for mood (OR: 1.88, p <
0.10). Results were similar after adjustment for WMH. CONCLUSIONS: slower
psychomotor speed may serve as a biomarker of risk of clinical disorders of
cognition, mobility and mood. While in part attributable to vascular brain
disease, other potentially modifiable contributors may be present. Further
studying the causes of psychomotor slowing with ageing might provide novel
insights into age-related brain disorders.
PMID- 27496933
TI - The accuracy of anatomical landmarks for locating the carotid sinus.
AB - BACKGROUND: carotid sinus massage (CSM) is a valuable clinical test for carotid
sinus syndrome (CSS) and relies on accurately locating the carotid sinus (CS).
OBJECTIVE: in this study, we sought to examine the accuracy of using anatomical
landmarks for locating the CS. METHODS: consecutive patients (n = 20) were
recruited prospectively. Two clinicians, trained in CSM, were asked to locate the
CS using anatomical landmarks. A point on the skin overlying the CS was then
marked by a vascular technician using ultrasound. Accuracy of techniques was
compared using intra-class correlation coefficients and Bland-Altman statistics.
RESULTS: anatomical landmarks underestimated the CS location by 1.5 +/- 1.3 cm.
Error extremes ranged from 4 cm below to 2 cm above CS using anatomical
landmarks. A moderate correlation between ultrasound and anatomical landmarks was
found, r = 0.371 (P = 0.031). CONCLUSION: this is the first study to characterise
the accuracy of standard anatomical landmarks used in CSM. Results suggest that
the point of maximal pulsation has the lowest associated error. Future work
should examine CSM yield across this and a range of other methodological factors.
PMID- 27496934
TI - A longitudinal comparative study of falls in persons with knee arthroplasty and
persons with or at high risk for knee osteoarthritis.
AB - OBJECTIVES: we determined the yearly prevalence of single and multiple falls in
persons with or at risk of knee osteoarthritis (OA) and persons undergoing knee
arthroplasty over an 8-year period. We also compared annual fall rates among
persons with and without knee arthroplasty to determine if fall rates are
associated with knee arthroplasty. METHODS: we studied 4,200 persons from the
Osteoarthritis Imitative (OAI), a National Institutes of Health funded
prospective study of persons 45-79 years and conducted from 2004 to 2012. All
either had knee OA or were at risk of developing knee OA but did not have knee
arthroplasty. The surgical group comprised 413 persons who underwent knee
arthroplasty. Key fall risk factors were assessed at yearly study visits.
Graphical depictions illustrated single and multiple fall trajectories.
Multinomial regression adjusted for potential confounders compared fall rates for
those with and without knee arthroplasty. RESULTS: fall rate trajectories for the
two samples were generally flat and fall rates were similar. For the arthroplasty
sample, fall rates did not increase in the immediate perioperative period
relative to earlier and later periods. No differences in fall rates were found
among the arthroplasty and non-arthroplasty samples after adjustment for
potential confounding (P > 0.05). CONCLUSIONS: fall rates were generally stable
and similar over an 8-year period among persons with and without knee
arthroplasty. Clinicians should not assume that persons undergoing knee
arthroplasty are at greater risk for falls either before or after surgery as
compared to persons with or at risk for knee OA.
PMID- 27496935
TI - The effect of aquatic exercise on physical functioning in the older adult: a
systematic review with meta-analysis.
AB - BACKGROUND: ageing and sedentary behaviour cause negative changes in the
neuromuscular systems of healthy older adults resulting in a decrease in physical
functioning. Exercising in water (aquatic exercise, AE) has been shown to be
effective at improving physical functioning in this population; however, no
systematic review with meta-analysis has been published. PURPOSE: to investigate
the effect of AE on physical functioning in healthy older adults compared to
control or land-based exercise (LE) through a systematic review with meta
analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, Cinahl,
PEDro, SPORTDiscus, Web of Science, Cochrane Library, published before 31st
December 2015. STUDY SELECTION: in total, 28 studies met the inclusion criteria
and were included in the systematic review; 24 studies with 1,456 subjects (89%
female) and with mean age 66.4 years were included in the meta-analysis. DATA
EXTRACTION: data were extracted and checked for accuracy by three independent
reviewers. DATA SYNTHESIS: size of treatment effect was measured using the
standardised mean difference with 95% confidence intervals (CIs). RESULTS:
compared to control interventions, AE had a moderate positive effect on physical
functioning 0.70 [95% CI 0.48 to 0.92]. Compared to LE, AE had a small positive
effect on physical functioning 0.39 [0.12 to 0.66]. LIMITATIONS: there is a high
risk of bias and low methodological quality in the studies particularly when
comparing AE to LE with possible over estimation of the benefit of AE.
CONCLUSIONS: AE may improve physical functioning in healthy older people and is
at least as effective as LE.
PMID- 27496936
TI - Thromboprophylaxis in atrial fibrillation and association with cognitive decline:
systematic review.
AB - OBJECTIVE: atrial fibrillation (AF) is associated with dementia. If AF-related
cognitive decline is driven by cerebral embolic events, thromboprophylaxis may
impact on this. This systematic review assessed the association between cognitive
impairment and AF thromboprophylaxis. METHODS: two independent reviewers searched
CINAHL, EMBASE, MEDLINE, PsycINFO, Web of Science Core Collection and Cochrane
Library from inception until 12 November 2014. Eligible studies compared AF
thromboprophylaxis to control with an outcome measure of cognition or dementia.
Where data allowed, meta-analyses describing between-group differences in
cognitive test scores or rates of incident dementia were performed. RESULTS:
nineteen studies were eligible. For two prospective studies (one randomised
controlled trial, RCT) comparing anticoagulation against antiplatelet therapy,
change in Mini-Mental Score Examination (MMSE) score from baseline to last follow
up (maximal duration: 5.9 years) suggested a difference favouring anticoagulation
(mean difference: 0.90, 95% CI: 0.29-1.51), in keeping with a trend seen in the
single RCT (mean difference MMSE: 0.80, 95% CI: -0.07 to 1.67). Pooled odds ratio
(OR) suggested no association with incident dementia, comparing anticoagulant to
antiplatelet therapy (two studies, OR: 1.23, 95% CI: 0.80-1.91) or no treatment
(three studies, OR: 0.89, 95% CI: 0.47-1.69). CONCLUSION: our analyses show no
definitive evidence of cognitive benefit or harm from anticoagulation. We
demonstrated a potential benefit of anticoagulation in comparison to antiplatelet
over time. Larger scale studies with longer follow-up are needed to determine the
true cognitive impact of AF thromboprophylaxis.
PMID- 27496937
TI - Older people remain on blood pressure agents despite being hypotensive resulting
in increased mortality and hospital admission.
AB - BACKGROUND: the use of antihypertensive medication in older people in order to
prevent cardiovascular events is well established. The use of such agents has
been encouraged by incentive schemes in the United Kingdom including the Quality
and Outcomes Framework. In addition, many guidelines recommend good blood
pressure (BP) control in the elderly. However, in older people antihypertensives
can cause adverse effects related to hypotension. AIM: the aim of this study was
to assess the prevalence of low BP and impact on outcomes, particularly in the
presence of antihypertensive treatment, in a primary care population of older
people. DESIGN: a retrospective observational cohort study in people over the age
of 70 years registered with primary care providers in Kent. RESULTS: a total of
11,167 patients over 70 years old were analysed, 6,373 female (57%). Systolic
blood pressure (SBP) was below 120 mmHg in 1,297 people (844 on
antihypertensives), below 110 mmHg in 474 (313 on antihypertensives) and below
100 mmHg in 128 (89 on antihypertensives). Hypotension was independently
associated with mortality, acute kidney injury and hospital admission.
CONCLUSIONS: the results demonstrate that low SBP is associated with adverse
events, it is possible that the pursuit of BP control at a population level may
lead to over-treatment in certain groups of patients. This may result in an
increased incidence of adverse events particularly in older people.
PMID- 27496938
TI - Prevalence and risk factors for falls in older men and women: The English
Longitudinal Study of Ageing.
AB - BACKGROUND: falls are a major cause of disability and death in older people.
Women are more likely to fall than men, but little is known about whether risk
factors for falls differ between the sexes. We used data from the English
Longitudinal Study of Ageing to investigate the prevalence of falls by sex and to
examine cross-sectionally sex-specific associations between a range of potential
risk factors and likelihood of falling. METHODS: participants were 4,301 men and
women aged 60 and over who had taken part in the 2012-13 survey of the English
Longitudinal Study of Ageing. They provided information about sociodemographic,
lifestyle and behavioural and medical factors, had their physical and cognitive
function assessed and responded to a question about whether they had fallen down
in the last two years. RESULTS: in multivariable logistic regression models,
severe pain and diagnosis of at least one chronic disease were independently
associated with falls in both sexes. Sex-specific risk factors were incontinence
(odds ratio (OR), 1.48; 95% CI, 1.19, 1.85) and frailty (OR 1.69, 95% CI 1.06,
2.69) in women, and older age (OR 1.02, 95% CI 1.04, 1.07), high levels of
depressive symptoms (OR 1.33, 95% CI 1.05, 1.68), and being unable to perform a
standing balance test (OR 3.32, 95% CI 2.09, 5.29) in men. CONCLUSION: although
we found some homogeneity between the sexes in the risk factors that were
associated with falls, the existence of several sex-specific risk factors
suggests that gender should be taken into account in designing fall-prevention
strategies.
PMID- 27496939
TI - New opioid analgesic use and the risk of injurious single-vehicle crashes in
drivers aged 50-80 years: A population-based matched case-control study.
AB - BACKGROUND: the increasing trend in opioid analgesic use among older drivers has
raised concerns about their risk of being involved in car crashes. AIM: to
investigate if older drivers who started using opioid analgesics have a higher
probability of being involved in injurious crashes. METHODS: population-based
matched case-control study. Data from population registers were merged using a
personal identity number. Cases were drivers aged 50-80 years responsible for a
single vehicle crash between 01.07.05 and 31.12.09 that led to at least one
injured passenger (n = 4,445). Four controls were randomly matched to each case
by sex, birth month/year, and residence area from persons holding a valid driving
license who did not crash during the study period. New use was defined as at
least one dispensation within 1-30 days prior to the crash, but none within the
previous 31-180 days; frequent use when >=3 dispensations were given within 0-180
days, with at least one within 31-180 days. Individuals using 1-2 non-opioid
analgesic medications were used as reference category. Conditional logistic
regression was used to estimate odds ratios (OR; 95% CI) adjusting for
benzodiazepine use, co-morbidity, civil status and occupation. RESULTS: adjusted
odds for new use were two-fold that of drivers using 1-2 non-opioid analgesics
medications (2.0; 1.6-2.5). For frequent use, adjusted odds were also increased
regardless of number of dispensations (3-4 = 1.7; 1.3-2.1, 5-6 = 1.6; 1.2-2.3,
and >=7 = 1.7; 1.3-2.1). CONCLUSION: new, but also frequent opioid analgesic use,
resulted in an increased probability of single vehicle crashes. While more
epidemiologic evidence is needed, patients could be advised to refrain from
driving when using opioid analgesics.
PMID- 27496940
TI - Missed diagnosis of pulmonary embolism with age-adjusted d-dimer cut-off value.
AB - Pulmonary embolism (PE) is a potentially severe diagnosis with high short-term
mortality. Recently, age-adjusted cut-off values (age * 10 MUg/l) of D-dimer were
introduced to improve the diagnostic workup in older patients. In clinical
practice, PE is considered 'ruled out' in patients with a non-high clinical
probability and a normal D-dimer. However, all diagnostic tests have a small
false-negative rate. This small probability of misdiagnosis might be easily
overlooked by clinicians when using simplified dichotomized flow charts. This
case illustrates a normal D-dimer (age-adjusted) but with a PE. We recommend
clinicians using the D-dimer test-either conventional or age-adjusted in a rule
out strategy to be aware of the-albeit small probability of a false-negative
result.
PMID- 27496941
TI - Melatonin, hypnotics and their association with fracture: a matched cohort study.
AB - OBJECTIVES: although melatonin prescribing in England has been increasing in
recent years, there have been no large scale studies on the safety of melatonin
compared to other medical treatments for insomnia. The primary aim of this study
was to examine the association between exposure to melatonin, hypnotic
benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone) and
fracture risk. DESIGN: retrospective cohort study. SETTING: 309 general practices
contributing to The Health Improvement Network (THIN) between 2008 and 2013.
PARTICIPANTS: 1,377 patients aged 45 years and older prescribed melatonin; 880
patients prescribed hypnotic benzodiazepines; 1,148 patients prescribed Z-drugs
and 2,752 unexposed controls matched by age, gender and practice. MAIN OUTCOME:
fracture following prescription of study drugs ascertained from practice records.
RESULTS: the unadjusted hazard ratios for fracture during the follow-up period
were 1.90 (95% CI 1.41-2.57) for melatonin, 1.70 (95% CI 1.18-2.46) for hypnotic
benzodiazepines and 2.03 (95% CI 1.45-2.84) for Z-drugs. After adjustment for 26
covariates, the hazard ratios were 1.44 (95% CI 1.01-2.04) for melatonin, 1.26
(95% CI 0.82-1.92) for hypnotic benzodiazepines and 1.52 (95% CI 1.04-2.23) for Z
drugs. Only patients with three or more melatonin prescriptions had elevated
risk. The mean time to fracture was 1.04 years and there was no significant
difference in mean time to fracture between the cohorts. CONCLUSIONS: in this
large cohort of patients attending UK primary care, prescriptions for melatonin
and Z-drugs were associated with a significantly increased risk of fracture. With
the use of melatonin increasing steadily overtime, this study adds to the
literature on the safety profile of this drug.
PMID- 27496942
TI - Social engagement and depressive symptoms: do baseline depression status and type
of social activities make a difference?
AB - OBJECTIVES: our purpose is to examine whether the association between social
engagement and depressive symptoms differs by initial level of depressive
symptoms and by the types of social engagement in which older adults engage.
DESIGN: persons aged 60 years and older in 2006 (n = 4,098) were drawn from Wave
1 of the Korean Longitudinal Study of Ageing and followed through Wave 3 (2010).
Growth curve analyses were conducted to identify the association between
engagement in multiple types of social activities and 4-year change in depressive
symptoms. Depression trajectories are examined separately by baseline depression
status. RESULTS: attending religious services was related to an increase in
depressive symptoms and participating in social gatherings with friends and
neighbours was related to a decrease in depressive symptoms, but only among
persons with CES-D 10 scale score below 10 at baseline. CONCLUSIONS: our findings
suggest that the positive effects of participating in social gatherings with
friends and family are manifest among older adults who have good mental health to
begin with. Our findings also suggest that the association between social
engagement and mental health varies by type of engagement and initial depression
level.
PMID- 27496944
TI - Nomogram to predict live birth rate after fertility-sparing surgery for
borderline ovarian tumours.
AB - STUDY QUESTION: Can a nomogram be used to predict the individual probability of
live birth (LB) in women with borderline ovarian tumours (BOTs) receiving primary
fertility-sparing surgery? SUMMARY ANSWER: A nomogram built according to the
woman's age, histological subtype (serous versus mucinous), type of ovarian
surgical treatment and FIGO stage can accurately predict the probability of LB in
women with BOT. WHAT IS KNOWN ALREADY: Current prediction models determine the
probability of pregnancy after medically assisted reproduction (MAR) and form the
basis of patient counselling to guide the decision as to whether to consider in
vitro fertilization but do not take into account prediction of the LB rate. STUDY
DESIGN, SIZE, DURATION: This was a retrospective multi-centre study including 187
women with fertility-sparing surgery for BOT diagnosed between January 1980 and
December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: A multivariate logistic
regression analysis of selected factors and a nomogram to predict the subsequent
LB rate was constructed. A bootstrapping technique was used for internal
validation. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-one women had LB (27.3%).
Taking into account multiple pregnancies, the overall LB rate was 40.1% (75/187).
Federation International of Gynaecology and Obstetric (FIGO) stage, age at
diagnosis, histological subtype and surgery type were included in the nomogram.
The predictive model had an AUC of 0.742 (95% CI, 0.644-0.825) and 0.72 (95% CI,
0.621-0.805) before and after the 200 repetitions of bootstrap sample
corrections, respectively, and showed a good calibration. LIMITATIONS, REASONS
FOR CAUTION: The retrospective nature of the study cannot exclude all biases. Our
nomogram is based on simple criteria, but did not take into account the
evaluation of ovarian reserve. It demonstrates a fair relevance, but requires
external validation before routine use. WIDER IMPLICATIONS OF THE FINDINGS:
Clinicians are increasingly interested in such tools to support the patient in
making an informed decision about treatment options. This nomogram contributes to
the decision-making by defining simple risk factors of poor LB probability that
can help identify good candidates for MAR. STUDY FUNDING/COMPETING INTERESTS: No
external funding was used for this study. There are no conflicts of interest to
declare. TRIAL REGISTRATION NUMBER: N/A.
PMID- 27496943
TI - Assisted reproductive technology in Europe, 2012: results generated from European
registers by ESHRE.
AB - STUDY QUESTION: The 16th European IVF-monitoring (EIM) report presents the data
of the treatments involving assisted reproductive technology (ART) and
intrauterine insemination (IUI) initiated in Europe during 2012: are there any
changes compared with previous years? SUMMARY ANSWER: Despite some fluctuations
in the number of countries reporting data, the overall number of ART cycles has
continued to increase year by year, the pregnancy rates (PRs) in 2012 remained
stable compared with those reported in 2011, and the number of transfers with
multiple embryos (3+) and the multiple delivery rates were lower than ever
before. WHAT IS KNOWN ALREADY: Since 1997, ART data in Europe have been collected
and re-ported in 15 manuscripts, published in Human Reproduction. STUDY DESIGN,
SIZE, DURATION: Retrospective data collection of European ART data by the EIM
Consortium for the European Society of Human Reproduction and Embryology (ESHRE).
Data for cycles between 1 January and 31 December 2012 were collected from
National Registers, when existing, or on a voluntary basis by personal
information. PARTICIPANTS/MATERIALS, SETTING, METHODS: From 34 countries (+1
compared with 2011), 1111 clinics reported 640 144 treatment cycles including 139
978 of IVF, 312 600 of ICSI, 139 558 of frozen embryo replacement (FER), 33 605
of egg donation (ED), 421 of in vitro maturation, 8433 of preimplantation genetic
diagnosis/preimplantation genetic screening and 5549 of frozen oocyte
replacements (FOR). European data on intrauterine insemination using
husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1126
IUI labs in 24 countries. A total of 175 028 IUI-H and 43 497 IUI-D cycles were
included. MAIN RESULTS AND THE ROLE OF CHANCE: In 18 countries where all clinics
reported to their ART register, a total of 369 081 ART cycles were performed in a
population of around 295 million inhabitants, corresponding to 1252 cycles per
million inhabitants (range 325-2732 cycles per million inhabitants). For all IVF
cycles, the clinical PRs per aspiration and per transfer were stable with 29.4
(29.1% in 2011) and 33.8% (33.2% in 2011), respectively. For ICSI, the
corresponding rates also were stable with 27.8 (27.9% in 2011) and 32.3% (31.8%
in 2011). In FER cycles, the PR per thawing/warming increased to 23.1% (21.3% in
2011). In ED cycles, the PR per fresh transfer increased to 48.4% (45.8% in 2011)
and to 35.9% (33.6% in 2011) per thawed transfer, while it was 45.1% for
transfers after FOR. The delivery rate after IUI remained stable, at 8.5% (8.3%
in 2011) after IUI-H and 12.0% (12.2% in 2011) after IUI-D. In IVF and ICSI
cycles, 1, 2, 3 and 4+ embryos were transferred in 30.2, 55.4, 13.3 and 1.1% of
the cycles, respectively. The proportions of singleton, twin and triplet
deliveries after IVF and ICSI (added together) were 82.1, 17.3 and 0.6%,
respectively, resulting in a total multiple delivery rate of 17.9% compared with
19.2% in 2011 and 20.6% in 2010. In FER cycles, the multiple delivery rate was
12.5% (12.2% twins and 0.3% triplets). Twin and triplet delivery rates associated
with IUI cycles were 9.0%/0.4% and 7.2%/0.5%, following treatment with husband
and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION: The method of
reporting varies among countries, and registers from a number of countries have
been unable to provide some of the relevant data such as initiated cycles and
deliveries. As long as data are incomplete and generated through different
methods of collection, results should be interpreted with caution. WIDER
IMPLICATIONS OF THE FINDINGS: The 16th ESHRE report on ART shows a continuing
expansion of the number of treatment cycles in Europe, with more than 640 000
cycles reported in 2012 with an increasing contribution to birthrate in many
countries. However, the need to improve and standardize the national registries,
and to establish validation methodologies remains manifest. STUDY
FUNDING/COMPETING INTERESTS: The study has no external funding; all costs are
covered by ESHRE. There are no competing interests.
PMID- 27496945
TI - The association of low ovarian reserve with cardiovascular disease risk: a cross
sectional population-based study.
AB - STUDY QUESTION: Is there a relationship between serum anti-Mullerian hormone
(AMH) level and cardiovascular disease (CVD) risk in premenopausal women? SUMMARY
ANSWER: There are indications that premenopausal women with very low ovarian
reserve may have an unfavorable CVD risk profile. WHAT IS KNOWN ALREADY: Age at
menopause is frequently linked to CVD occurrence. AMH is produced by ovarian
antral follicles and provides a measure of remaining ovarian reserve Literature
on whether AMH is related to CVD risk is still scarce and heterogeneous. STUDY
DESIGN, SIZE, DURATION: Cross-sectional study in 2338 women (age range of 20-57
years) from the general population, participating in the Doetinchem Cohort Study
between 1993 and 1997. PARTICIPANTS/MATERIALS, SETTING, METHODS: CVD risk was
compared between 2338 premenopausal women in different AMH level-categories, with
adjustment for confounders. CVD risk was assessed through levels of systolic and
diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol
and glucose, in addition to a summed score of CVD risk factors. Among other
factors, analyses were corrected for smoking, oral contraceptive use and BMI.
MAIN RESULTS AND THE ROLE OF CHANCE: The relationship of serum AMH levels with
CVD risk factor outcomes was nonlinear. Women with AMH levels <0.16 ug/l had 0.11
(95% confidence intervals (CIs) 0.01; 0.21) more metabolic risk factors compared
with women with AMH levels >=0.16 ug/l. There was no association of individual
risk factor levels with AMH levels, besides a tendency towards lower total
cholesterol levels of 0.11 mmol/l (95% CI -0.23; 0.01) in women with AMH levels
<0.002 ug/l compared with women with AMH levels >=0.16 ug/l. Although not
statistically significant, these effect sizes were larger in women below 40 years
of age. LIMITATIONS, REASONS FOR CAUTION: Causality and temporality of the
studied association cannot be addressed here. Moreover, the clinical and
statistical significance of the results of this exploratory study should be
interpreted with caution due to the absence of adjustment for multiple
statistical testing. WIDER IMPLICATIONS OF THE FINDINGS: This population-based
study supports previous findings that premenopausal women with very low AMH
levels may have an increased CVD risk. It lays the groundwork for future research
to focus on this group of women. Longitudinal studies with more sensitive AMH
assays may furthermore help better understand the implications of these results.
STUDY FUNDING/COMPETING INTEREST: No financial support was received for this
research or manuscript. The Doetinchem Cohort Study is conducted and funded by
the Dutch National Institute for Public Health and the Environment F.J.M.B. has
received fees and grant support from Merck Serono, Gedeon Richter, Ferring BV and
Roche. TRIAL REGISTRATION NUMBER: N/A.
PMID- 27496946
TI - Vitamin D deficiency and low ionized calcium are linked with semen quality and
sex steroid levels in infertile men.
AB - STUDY QUESTION: Are low vitamin D levels linked with semen quality and sex
steroids in infertile men? SUMMARY ANSWER: Infertile men with vitamin D
deficiency had lower sperm motility, total numbers of motile sperm, Inhibin B,
sex-hormone-binding-globulin (SHBG) and testosterone/estradiol ratio, but higher
levels of free sex steroids, than infertile men with normal vitamin D levels.
WHAT IS KNOWN ALREADY: Low vitamin D levels have been associated with decreased
sperm motility in healthy men, but a relationship between vitamin D and calcium
with semen quality and especially sex steroids has not been sufficiently
described in infertile men. STUDY DESIGN, SIZE, DURATION: This study comprises
baseline characteristics of 1427 infertile men screened from 2011 to 2014 for
inclusion in a randomized clinical trial, the Copenhagen-Bone-Gonadal Study.
PARTICIPANTS/MATERIALS, SETTING, METHODS: In total 1427 infertile men,
consecutively referred to our tertiary andrological centre for fertility workup,
underwent a physical examination and had semen quality assessed based on two
samples and blood analysed for serum testosterone, SHBG, estradiol, inhibin B,
luteinizing hormone, follicle-stimulating hormone (FSH), 25-hydroxyvitamin D (25
OHD), ionized calcium (Ca(2+)) and karyotype. There were 179 men excluded due to
serious comorbidities or anabolic steroid usage, leaving 1248 patients for
analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Men with 25-OHD >75 nmol/l had
higher sperm motility and 66 and 111% higher total numbers of motile spermatozoa
after 45 and 262 min, respectively, than men with 25-OHD <25 nmol/l (all P <
0.05). SHBG levels and testosterone/estradiol ratios were 15 and 14% lower,
respectively, while free testosterone and estradiol ratios were 6 and 13% higher,
respectively, in men with 25-OHD <25 nmol/l (all P < 0.05). Men with lower Ca(2+)
levels had higher progressive sperm motility and inhibin B/FSH ratio but lower
testosterone/estradiol ratio (all P < 0.05). LIMITATIONS, REASONS FOR CAUTION:
All outcomes presented are predefined end-points but inferral of causality is
compromised by the descriptive study design. It remains to be shown whether the
links between vitamin D, calcium, semen quality and sex steroids in infertile men
are causal. WIDER IMPLICATIONS OF THE FINDINGS: The associations between vitamin
D deficiency and low calcium with semen quality and sex steroids support the
existence of a cross-link between regulators of calcium homeostasis and gonadal
function in infertile men. STUDY FUNDING/COMPETING INTERESTS: This study was
supported by the Danish Agency for Science, Technology and Innovation, Horslev
Fonden, Danish Cancer Society and Novo Nordisk Foundation. There are no conflicts
of interest. TRIAL REGISTRATION NUMBER: NCT01304927. DATE OF TRIAL REGISTRATION:
25 February 2011. DATE OF ENROLMENT OF FIRST PATIENT: 8 March 2011.
PMID- 27496947
TI - Maternal first trimester serum levels of free-beta human chorionic gonadotrophin
and male genital anomalies.
AB - STUDY QUESTION: Are maternal first trimester levels of serum free-beta hCG
associated with the development of hypospadias or undescended testis (UDT) in
boys? SUMMARY ANSWER: Overall, first trimester maternal levels of serum free-beta
hCG are not associated with hypospadias or UDT. However, elevated levels were
found in severe phenotypes (proximal hypospadias and bilateral UDT) suggesting an
altered pathway of hormonal release in early pregnancy. WHAT IS KNOWN ALREADY:
Human chorionic gonadotrophin peaks in first trimester of pregnancy stimulating
fetal testosterone production, which is key to normal male genital development.
Endocrine-disrupting insults early in pregnancy have been associated with
increased risk of common genital anomalies in males such as hypospadias and UDT.
One plausible etiological pathway is altered release of hCG. STUDY DESIGN, SIZE,
DURATION: We conducted a record-linkage study of two separate populations of
women attending first trimester aneuploidy screening in two Australian states,
New South Wales (NSW) and Western Australia (WA), in 2006-2009 and 2001-2003,
respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: Included were women who
gave birth to a singleton live born male infant. There were 12 099 boys from NSW
and 10 518 from WA included, of whom 90 and 77 had hypospadias; and 107 and 109
UDT, respectively. Serum levels of free-beta hCG were ascertained from laboratory
databases and combined with relevant birth outcomes and congenital anomalies via
record linkage of laboratory, birth, congenital anomalies and hospital data.
Median and quartile levels of gestational age specific free-beta hCG multiple of
the median (MoM) were compared between affected and unaffected boys. Logistic
regression was used to evaluate the association between levels of free-beta hCG
MoM and hypospadias or UDT, stratified by suspected placental dysfunction and co
existing anomalies. Where relevant, pooled analysis was conducted. MAIN RESULTS
AND THE ROLE OF CHANCE: There was no difference in median hCG levels amongst
women with an infant with hypospadias (NSW = 0.88 MoM, P = 0.83; WA = 0.84 MoM, P
= 0.76) or UDT (NSW = 0.89 MoM, P = 0.54; WA = 0.95 MoM, P = 0.95), compared with
women with an unaffected boy (NSW = 0.92 MoM; WA = 0.88 MoM). Low (<25th centile)
or high (>75th centile) hCG levels were not associated with hypospadias or UDT,
nor when stratifying by suspected placental dysfunction and co-existing
anomalies. However, there was a tendency towards high levels for severe types,
although confidence intervals were wide. When combining NSW and WA results, high
hCG MoM levels (>75th centile) were associated with increased risk of proximal
hypospadias (odds ratio (OR) 4.34; 95% CI: 1.08-17.4) and bilateral UDT (OR 2.86;
95% CI: 1.02-8.03). LIMITATIONS, REASONS FOR CAUTION: There were only small
numbers of proximal hypospadias and bilateral UDT in both cohorts and although we
conducted pooled analyses, results reported on these should be interpreted with
caution. Gestational age by ultrasound may have been inaccurately estimated in
small and large for gestational age fetuses affecting hCG MoM calculation in
those pregnancies. Despite the reliability of our datasets in identifying adverse
pregnancy outcomes, we did not have pathology information to confirm tissue
lesions in the placenta and therefore our composite outcome should be considered
as a proxy for placental dysfunction. WIDER IMPLICATIONS OF THE FINDINGS: This is
one of the largest population-based studies examining the association between
maternal first trimester serum levels of free-beta hCG and genital anomalies
hypospadias and UDT; and the first to compare specific phenotypes by severity.
Overall, our findings does not support the hypothesis that alteration in maternal
hCG levels is associated with the development of male genital anomalies; however,
high hCG free-beta levels found in severe types suggest different underlying
etiology involving higher production and secretion of hCG. These findings require
further exploration and replication. STUDY FUNDING/COMPETING INTERESTS: This work
was funded by the National Health and Medical Research Council (NHMRC) grant
APP1047263. N.N. is supported by a NHMRC Career Development Fellowship
APP1067066. C.B. was supported by a NHMRC Principal Research Fellowship #634341.
The funding agencies had no role in the design, analysis, interpretation or
reporting of the findings. There are no competing interests. TRIAL REGISTRATION
NUMBER: Not applicable.
PMID- 27496948
TI - Novel Mechanisms for Heme-dependent Degradation of ALAS1 Protein as a Component
of Negative Feedback Regulation of Heme Biosynthesis.
AB - In eukaryotic cells, heme production is tightly controlled by heme itself through
negative feedback-mediated regulation of nonspecific 5-aminolevulinate synthase
(ALAS1), which is a rate-limiting enzyme for heme biosynthesis. However, the
mechanism driving the heme-dependent degradation of the ALAS1 protein in
mitochondria is largely unknown. In the current study, we provide evidence that
the mitochondrial ATP-dependent protease ClpXP, which is a heteromultimer of CLPX
and CLPP, is involved in the heme-dependent degradation of ALAS1 in mitochondria.
We found that ALAS1 forms a complex with ClpXP in a heme-dependent manner and
that siRNA-mediated suppression of either CLPX or CLPP expression induced ALAS1
accumulation in the HepG2 human hepatic cell line. We also found that a specific
heme-binding motif on ALAS1, located at the N-terminal end of the mature protein,
is required for the heme-dependent formation of this protein complex. Moreover,
hemin-mediated oxidative modification of ALAS1 resulted in the recruitment of
LONP1, another ATP-dependent protease in the mitochondrial matrix, into the ALAS1
protein complex. Notably, the heme-binding site in the N-terminal region of the
mature ALAS1 protein is also necessary for the heme-dependent oxidation of ALAS1.
These results suggest that ALAS1 undergoes a conformational change following the
association of heme to the heme-binding motif on this protein. This change in the
structure of ALAS1 may enhance the formation of complexes between ALAS1 and ATP
dependent proteases in the mitochondria, thereby accelerating the degradation of
ALAS1 protein to maintain appropriate intracellular heme levels.
PMID- 27496949
TI - A Targeted Mutation Identified through pKa Measurements Indicates a
Postrecruitment Role for Fis1 in Yeast Mitochondrial Fission.
AB - The tail-anchored protein Fis1 is implicated as a passive tether in yeast
mitochondrial fission. We probed the functional role of Fis1 Glu-78, whose
elevated side chain pKa suggests participation in protein interactions. Fis1
binds partners Mdv1 or Dnm1 tightly, but mutation E78A weakens Fis1 interaction
with Mdv1, alters mitochondrial morphology, and abolishes fission in a growth
assay. In fis1Delta rescue experiments, Fis1-E78A causes a novel localization
pattern in which Dnm1 uniformly coats the mitochondria. By contrast, Fis1-E78A at
lower expression levels recruits Dnm1 into mitochondrial punctate structures but
fails to support normal fission. Thus, Fis1 makes multiple interactions that
support Dnm1 puncta formation and may be essential after this step, supporting a
revised model for assembly of the mitochondrial fission machinery. The insights
gained by mutating a residue with a perturbed pKa suggest that side chain pKa
values inferred from routine NMR sample pH optimization could provide useful
leads for functional investigations.
PMID- 27496952
TI - The limbus of the fossa ovalis: an unusual location for incessant focal atrial
tachycardia in children.
PMID- 27496950
TI - Instability of the Human Cytochrome P450 Reductase A287P Variant Is the Major
Contributor to Its Antley-Bixler Syndrome-like Phenotype.
AB - Human NADPH-cytochrome P450 oxidoreductase (POR) gene mutations are associated
with severe skeletal deformities and disordered steroidogenesis. The human POR
mutation A287P presents with disordered sexual development and skeletal
malformations. Difficult recombinant expression and purification of this POR
mutant suggested that the protein was less stable than WT. The activities of
cytochrome P450 17A1, 19A1, and 21A2, critical in steroidogenesis, were similar
using our purified, full-length, unmodified A287P or WT POR, as were those of
several xenobiotic-metabolizing cytochromes P450, indicating that the A287P
protein is functionally competent in vitro, despite its functionally deficient
phenotypic behavior in vivo Differential scanning calorimetry and limited
trypsinolysis studies revealed a relatively unstable A287P compared with WT
protein, leading to the hypothesis that the syndrome observed in vivo results
from altered POR protein stability. The crystal structures of the soluble domains
of WT and A287P reveal only subtle differences between them, but these
differences are consistent with the differential scanning calorimetry results as
well as the differential susceptibility of A287P and WT observed with
trypsinolysis. The relative in vivo stabilities of WT and A287P proteins were
also examined in an osteoblast cell line by treatment with cycloheximide, a
protein synthesis inhibitor, showing that the level of A287P protein post
inhibition is lower than WT and suggesting that A287P may be degraded at a higher
rate. Current studies demonstrate that, unlike previously described mutations,
A287P causes POR deficiency disorder due to conformational instability leading to
proteolytic susceptibility in vivo, rather than through an inherent flavin
binding defect.
PMID- 27496951
TI - Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis
elegans and Mammalian Adipocytes.
AB - Protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent protein kinase composed
of catalytic and regulatory subunits and involved in various physiological
phenomena, including lipid metabolism. Here we demonstrated that the
stoichiometric balance between catalytic and regulatory subunits is crucial for
maintaining basal PKA activity and lipid homeostasis. To uncover the potential
roles of each PKA subunit, Caenorhabditis elegans was used to investigate the
effects of PKA subunit deficiency. In worms, suppression of PKA via RNAi resulted
in severe phenotypes, including shortened life span, decreased egg laying,
reduced locomotion, and altered lipid distribution. Similarly, in mammalian
adipocytes, suppression of PKA regulatory subunits RIalpha and RIIbeta via siRNAs
potently stimulated PKA activity, leading to potentiated lipolysis without
increasing cAMP levels. Nevertheless, insulin exerted anti-lipolytic effects and
restored lipid droplet integrity by antagonizing PKA action. Together, these data
implicate the importance of subunit stoichiometry as another regulatory mechanism
of PKA activity and lipid metabolism.
PMID- 27496953
TI - Assessing cardiac autonomic function via heart rate variability analysis requires
monitoring respiration.
PMID- 27496954
TI - Assessing cardiac autonomic function via heart rate variability analysis requires
monitoring respiration: reply.
PMID- 27496955
TI - Access to and clinical use of cardiac implantable electronic devices and
interventional electrophysiological procedures in the European Society of
Cardiology Countries: 2016 Report from the European Heart Rhythm Association.
AB - AIMS: The aim of this analysis was to provide comprehensive information on the
access to and use of cardiac implantable electronic device (CIED) and catheter
ablation therapy in the European Society of Cardiology (ESC) area. METHODS AND
RESULTS: The European Heart Rhythm Association (EHRA) has been collecting
descriptive and quantitative data on invasive arrhythmia therapies since 2008.
This year 50 of the 56 ESC member countries provided data for the EHRA White
Book. Up-to-date information on procedure rates for the last 5 years together
with information on demographics, economy, vital statistics, local healthcare
systems, and training activities is presented for each country and the 5
geographical ESC regions. Our analysis indicated that considerable heterogeneity
in the access to arrhythmia therapies still exists across the ESC area. In 2015,
the CIED implantation rates per million population were highest in the Western
followed by the Southern and Northern European countries. The catheter ablation
activity was largest in the Western followed by the Northern and Southern areas.
Overall, the procedure rates were 3-10 times higher in the European than in the
non-European ESC countries. Economic resources were not the only driver for
utilization of arrhythmia therapies as in some Eastern European countries with
relative low gross domestic product the procedure rates exceeded the average
values. CONCLUSION: These data will help the healthcare professionals and
stakeholders to identify and to understand in more depth the trends, disparities,
and gaps in cardiac arrhythmia care and thereby promote harmonization of cardiac
arrhythmias therapies in the ESC area.
PMID- 27496956
TI - Opioid analgesics and chronic non-cancer pain: a prescription for research in
primary care.
PMID- 27496957
TI - Regulatory Function of Hexokinase 2 in Glucose Signaling in Saccharomyces
cerevisiae.
PMID- 27496958
TI - The Nuclear Hexokinase 2 Acts as a Glucose Sensor in Saccharomyces cerevisiae.
PMID- 27496959
TI - PKD1 protein is involved in reactive oxygen species-mediated mitochondrial
depolarization in cooperation with protein kinase Cdelta (PKCdelta).
PMID- 27496960
TI - Cross-talk between insulin and Wnt signaling in preadipocytes. ROLE OF Wnt CO
RECEPTOR LDL RECEPTOR-RELATED PROTEIN-5 (LRP5).
PMID- 27496961
TI - Celastrol, a triterpene, enhances TRAIL-induced apoptosis through the down
regulation of cell survival proteins and up-regulation of death receptors.
PMID- 27496962
TI - Crotepoxide chemosensitizes tumor cells through inhibition of expression of
proliferation, invasion, and angiogenic proteins linked to proinflammatory
pathway.
PMID- 27496963
TI - gamma-Tocotrienol but not gamma-tocopherol blocks STAT3 cell signaling pathway
through induction of protein-tyrosine phosphatase SHP-1 and sensitizes tumor
cells to chemotherapeutic agents.
PMID- 27496964
TI - Gossypol induces death receptor-5 through activation of ROS-ERK-CHOP pathway and
sensitizes colon cancer cells to TRAIL.
PMID- 27496965
TI - Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis
through p53-independent up-regulation of death receptors. EVIDENCE FOR THE ROLE
OF REACTIVE OXYGEN SPECIES AND JNK.
PMID- 27496966
TI - Nimbolide sensitizes human colon cancer cells to TRAIL through reactive oxygen
species- and ERK-dependent up-regulation of death receptors, p53, and Bax.
PMID- 27496967
TI - 3-Formylchromone interacts with cysteine 38 in p65 protein and with cysteine 179
in IkappaBalpha kinase, leading to down-regulation of nuclear factor-kappaB (NF
kappaB)-regulated gene products and sensitization of tumor cells.
PMID- 27496968
TI - Acute leukaemia and myelodysplastic syndromes with chromosomal rearrangement
involving 11q23 locus, but not MLL gene.
AB - AIMS: Chromosome 11q23 translocations, resulting in MLL (KMT2A) rearrangement,
have been well characterised in acute myeloid leukaemia (AML) and acute
lymphoblastic leukaemia (ALL). However, little is known of haematopoietic
neoplasms associated with 11q23 translocation but without MLL rearrangement
(11q23+/MLL-). The aim of this study is to characterise such cases with
11q23+/MLL-. METHODS AND RESULTS: We retrospectively searched our database for
cases with haematopoietic malignancies with 11q23+/MLL-. We identified nine
patients, two with AML, two with B-lymphoblastic leukaemia (B-ALL); two with T
lymphoblastic leukaemia (T-ALL), two with myelodysplastic syndrome (MDS) and one
with chronic myelomonocytic leukaemia (CMML). The translocations included
t(X;11)(p11.2;q23), t(2;11)(p21;q23), t(6;11)(q27;q23), t(8;9;11)(q13;q13;q23),
t(11;11)(p15;q23), t(11;14)(q23;q24) and t(11;15)(q23;q14). Five of six patients
with acute leukaemia had received chemotherapy and detection of 11q23
translocation occurred at time of disease relapse. Both patients with MDS and the
patient with CMML had 11q23 translocation detected at time of initial diagnosis,
all three patients progressed to AML after >1 year on hypomethylating agent
therapy. All patients received risk-adapted therapies, including stem cell
transplant in five patients. At the last follow-up, eight patients died with a
median overall survival of 14 months. CONCLUSIONS: 11q23+/MLL- occurs rarely,
involving different partner chromosomes and showing clinical and pathological
features and disease subtypes different from those cases with MLL rearrangement.
11q23+/MLL- appears to be associated with clonal evolution/disease progression in
acute leukaemia, a high risk for AML progression in MDS/CMML and a high incidence
of disease relapse.
PMID- 27496969
TI - DNA hypermethylation analysis in sputum of asymptomatic subjects at risk for lung
cancer participating in the NELSON trial: argument for maximum screening interval
of 2 years.
AB - AIMS: Lung cancer is the major contributor to cancer mortality due to
metastasised disease at time of presentation. The current study investigated DNA
hypermethylation of biomarkers RASSF1A, APC, cytoglobin, 3OST2, FAM19A4, PHACTR3
and PRDM14 in sputum of asymptomatic high-risk individuals from the NELSON lung
cancer low-dose spiral CT screening trial to detect lung cancer at preclinical
stage. METHODS: Subjects were selected with (i) lung cancer in follow-up (cases;
n=65), (ii) minor cytological aberrations (controls; n=120) and (iii) a random
selection of subjects without cytological aberrations (controls; n=99). Median
follow-up time for controls was 80 months. Cut-off values were based on high
specificity to assess diagnostic value of the biomarkers. RESULTS: RASSF1A may
denote presence of invasive cancer because of its high specificity (93% (95% CI
89% to 96%); sensitivity 17% (95% CI 4% to 31%), with best performance in a
screening interval of 2 years. The panel of RASSF1A, 3OST2 and PRDM14 detected
28% (95% CI 11% to 44%) of lung cancer cases within 2 years, with specificity of
90% (95% CI 86% to 94%). Sputum cytology did not detect any lung cancers.
CONCLUSIONS: In a lung cancer screening setting with maximum screening interval
of 2 years, DNA hypermethylation analysis in sputum may play a role in the
detection of preclinical disease, but complementary diagnostic markers are needed
to improve sensitivity.
PMID- 27496970
TI - Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in
Offspring Thymus.
AB - Using multiple murine foster-nursing protocols, thereby eliminating placental
transfer and allowing a distinction between dam- and pup-derived cells, we show
that foster nursing by an immunized dam results in development of CD8(+) T cells
in nonimmunized foster pups that are specific for Ags against which the foster
dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have
dubbed this process "maternal educational immunity" to distinguish it from
passive cellular immunity. Of the variety of maternal immune cells present in
milk, only T cells were detected in pup tissues. Maternal T cells, a substantial
percentage of which were CD4(+)MHC class II(+), accumulated in the pup thymus and
spleen during the nursing period. Further analysis of maternal cells in the pup
thymus showed that a proportion was positive for maternal immunogen-specific MHC
class II tetramers. To determine the outcome of Ag presentation in the thymus,
the maternal or foster pup origin of immunogen-responding CD8(+) cells in foster
pup spleens was assessed. Whereas ~10% were maternally derived in the first few
weeks after weaning, all immunogen-responding CD8(+) T cells were pup derived by
12 wk of age. Pup-derived immunogen-responsive CD8(+) cells persisted until at
least 1 y of age. Passive cellular immunity is well accepted and has been
demonstrated in the human population. In this study, we show an arguably more
important role for transferred immune cells: the direction of offspring T cell
development. Harnessing maternal educational immunity through prepregnancy
immunization programs has potential for improvement of infant immunity.
PMID- 27496972
TI - Zebrafish IRF1, IRF3, and IRF7 Differentially Regulate IFNPhi1 and IFNPhi3
Expression through Assembly of Homo- or Heteroprotein Complexes.
AB - In mammals, IFN regulatory factor (IRF)1, IRF3, and IRF7 are three critical
transcription factors that are pivotal for cooperative regulation of the type I
IFN response. In this study, we explored the relative contribution of zebrafish
(Danio rerio) IRF1 (DrIRF1), IRF3 (DrIRF3), and IRF7 (DrIRF7) (DrIRF1/3/7) to
zebrafish IFNPhi1 (DrIFNPhi1) and IFNPhi3 (DrIFNPhi3) (DrIFNPhi1/3) activation.
Following spring viremia of carp virus infection, DrIFNPhi1/3 and DrIRF1/3/7
transcripts are significantly induced in zebrafish tissues, which correlates with
the replication of spring viremia of carp virus. DrIRF1/3/7 selectively bind to
the IRF-binding element/IFN-stimulated regulatory element sites of DrIFNPhi1/3
promoters, with the exception that DrIRF3 has no preference for two IRF-binding
element/IFN-stimulated regulatory element motifs within the DrIFNPhi3 promoter.
Consistently, DrIRF3 alone activates DrIFNPhi1, but not DrIFNPhi3; DrIRF7
predominantly stimulates DrIFNPhi3; and DrIRF1 has similar potential to DrIFNPhi1
and DrIFNPhi3. Strikingly, DrIRF3 facilitates the binding of DrIRF1 and DrIRF7 to
both zebrafish IFN promoters, and so does DrIRF7 for the binding of DrIRF1,
particularly to the DrIFNPhi3 promoter. These binding properties correlate with
differential responses of DrIFNPhi1 and DrIFNPhi3 to the combinatory stimulation
of DrIRF1/3/7, depending on their relative amounts. Similar to the dual roles of
human IRF3 in regulating IRF7-activated IFNalpha genes, DrIRF3 exerts dual
effects on DrIRF1-mediated DrIFNPhi3 gene expression: an inhibitory effect at
lower concentrations and a synergistic effect at higher concentrations. These
data provide evidence that fish and mammals have evolved a similar IRF-dependent
regulatory mechanism fine-tuning IFN gene activation.
PMID- 27496971
TI - The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To
Promote Th9 Cell Development.
AB - The IL-9-secreting Th9 subset of CD4 Th cells develop in response to an
environment containing IL-4 and TGF-beta, promoting allergic disease,
autoimmunity, and resistance to pathogens. We previously identified a requirement
for the ETS family transcription factor PU.1 in Th9 development. In this report,
we demonstrate that the ETS transcription factor ETS variant 5 (ETV5) promotes IL
9 production in Th9 cells by binding and recruiting histone acetyltransferases to
the Il9 locus at sites distinct from PU.1. In cells that are deficient in both
PU.1 and ETV5 there is lower IL-9 production than in cells lacking either factor
alone. In vivo loss of PU.1 and ETV5 in T cells results in distinct effects on
allergic inflammation in the lung, suggesting that these factors function in
parallel. Together, these data define a role for ETV5 in Th9 development and
extend the paradigm of related transcription factors having complementary
functions during differentiation.
PMID- 27496973
TI - T Cell Fates Zipped Up: How the Bach2 Basic Leucine Zipper Transcriptional
Repressor Directs T Cell Differentiation and Function.
AB - Recent data illustrate a key role for the transcriptional regulator bric-a-brac,
tramtrack, and broad complex and cap'n'collar homology (Bach)2 in orchestrating T
cell differentiation and function. Although Bach2 has a well-described role in B
cell differentiation, emerging data show that Bach2 is a prototypical member of a
novel class of transcription factors that regulates transcriptional activity in T
cells at super-enhancers, or regions of high transcriptional activity.
Accumulating data demonstrate specific roles for Bach2 in favoring regulatory T
cell generation, restraining effector T cell differentiation, and potentiating
memory T cell development. Evidence suggests that Bach2 regulates various facets
of T cell function by repressing other key transcriptional regulators such as B
lymphocyte-induced maturation protein 1. In this review, we examine our present
understanding of the role of Bach2 in T cell function and highlight the growing
evidence that this transcriptional repressor functions as a key regulator
involved in maintenance of T cell quiescence, T cell subset differentiation, and
memory T cell generation.
PMID- 27496975
TI - Critique of World Health Organization Recommendation of a Dengue Vaccine.
PMID- 27496974
TI - Chikungunya Virus: In Vitro Response to Combination Therapy With Ribavirin and
Interferon Alfa 2a.
AB - INTRODUCTION: We evaluated the antiviral activities of ribavirin (RBV) and
interferon (IFN) alfa as monotherapy and combination therapy against chikungunya
virus (CHIKV). METHODS: Vero cells were infected with CHIKV in the presence of
RBV and/or IFN alfa, and viral production was quantified by plaque assay. A
mathematical model was fit to the data to identify drug interactions for effect.
We ran simulations using the best-fit model parameters to predict the antiviral
activity associated with clinically relevant regimens of RBV and IFN alfa as
combination therapy. The model predictions were validated using the hollow fiber
infection model (HFIM) system. RESULTS: RBV and IFN alfa were effective against
CHIKV as monotherapy at supraphysiological concentrations. However, RBV and IFN
alfa were highly synergistic for antiviral effect when administered as
combination therapy. Simulations with our mathematical model predicted that a
standard clinical regimen of RBV plus IFN alfa would inhibit CHIKV burden by 2.5
log10 following 24 hours of treatment. In the HFIM system, RBV plus IFN alfa at
clinical exposures resulted in a 2.1-log10 decrease in the CHIKV burden following
24 hours of therapy. These findings validate the prediction made by the
mathematical model. CONCLUSIONS: These studies illustrate the promise of RBV plus
IFN alfa as a potential therapeutic strategy for the treatment of CHIKV
infections.
PMID- 27496976
TI - Infection-Induced Vascular Permeability Aids Mycobacterial Growth.
AB - Pathogenic mycobacteria trigger formation of organized granulomas. As granulomas
mature, they induce angiogenesis and vascular permeability. Here, in a striking
parallel to tumor pro-angiogenic signaling, we identify angiopoietin-2 (ANG-2)
induction as an important component of vascular dysfunction during mycobacterial
infection. Mycobacterial infection in humans and zebrafish results in robust
induction of ANG-2 expression from macrophages and stromal cells. Using a small
molecule inhibitor closely related to one currently in clinical trials, we link
ANG-2/TIE2 signaling to vascular permeability during mycobacterial infection.
Targeting granuloma-induced vascular permeability via vascular endothelial
protein tyrosine phosphatase inhibition limits mycobacterial growth, suggesting a
new strategy for host-directed therapies against tuberculosis.
PMID- 27496977
TI - Population Perspectives and World Health Organization Recommendations for CYD-TDV
Dengue Vaccine.
PMID- 27496979
TI - Dietary fiber and the short-chain fatty acid acetate promote resolution of
neutrophilic inflammation in a model of gout in mice.
AB - : Gout is a disease characterized by the deposition of monosodium urate (MSU)
crystals in the joints. Continuous gout episodes may lead to unresolved
inflammatory responses and tissue damage. We investigated the effects of a high
fiber diet and acetate, a short-chain fatty acid (SCFA) resulting from the
metabolism of fiber by gut microbiota, on the inflammatory response in an
experimental model of gout in mice. Injection of MSU crystals into the knee joint
of mice induced neutrophil influx and inflammatory hypernociception. The onset of
inflammatory response induced by MSU crystals was not altered in animals given a
high-fiber diet, but the high-fiber diet induced faster resolution of the
inflammatory response. Similar results were obtained in animals given the SCFA
acetate. Acetate was effective, even when given after injection of MSU crystals
at the peak of the inflammatory response and induced caspase-dependent apoptosis
of neutrophils that accounted for the resolution of inflammation. Resolution of
neutrophilic inflammation was associated with decreased NF-kappaB activity and
enhanced production of anti-inflammatory mediators, including IL-10, TGF-beta,
and annexin A1. Acetate treatment or intake of a high-fiber diet enhanced
efferocytosis, an effect also observed in vitro with neutrophils treated with
acetate. In conclusion, a high-fiber diet or one of its metabolic products,
acetate, controls the inflammatory response to MSU crystals by favoring the
resolution of the inflammatory response. Our studies suggest that what we eat
plays a determinant role in our capacity to fine tune the inflammatory response.
INTRODUCTION:
PMID- 27496980
TI - The case for better case reports....
PMID- 27496978
TI - Efficacy of Vesicular Stomatitis Virus-Ebola Virus Postexposure Treatment in
Rhesus Macaques Infected With Ebola Virus Makona.
AB - The Ebola virus (EBOV) epidemic in West Africa increased the focus on vaccine
development against this hemorrhagic fever-causing pathogen, and as a consequence
human clinical trials for a few selected platforms were accelerated. One of these
vaccines is vesicular stomatitis virus (VSV)-EBOV, also known as rVSV-ZEBOV, a
fast-acting vaccine against EBOV and so far the only vaccine with reported
efficacy against EBOV infections in humans in phase III clinical trials. In this
study, we analyzed the potential of VSV-EBOV for postexposure treatment of rhesus
macaques infected with EBOV-Makona. We treated groups of animals with 1 dose of
VSV-EBOV either in a single injection at 1 or 24 hours after EBOV exposure or
with 2 injections, half the dose at each time point; 1 control group received the
same dose of the VSV-based Marburg virus vaccine at both time points; another
group remained untreated. Although all untreated animals succumbed to EBOV
infection, 33%-67% of the animals in each treatment group survived the infection,
including the group treated with the VSV-based Marburg virus vaccine. This result
suggests that protection from postexposure vaccination may be antigen unspecific
and due rather to an early activation of the innate immune system. In conclusion,
VSV-EBOV remains a potent and fast-acting prophylactic vaccine but demonstrates
only limited efficacy in postexposure treatment.
PMID- 27496981
TI - Thirty years of hand therapy: The 2014 practice analysis.
AB - STUDY DESIGN: Quantitative and descriptive study. INTRODUCTION: In 2014, the Hand
Therapy Certification Commission (HTCC), in consultation with Professional
Examination Service, performed a practice analysis study of hand therapy, the
fifth in a series of similar studies performed by HTCC over a 30-year period.
PURPOSE: The purpose of the study was to gather data on current hand therapy
practice to ensure the content of the Certified Hand Therapist (CHT) examination
and credentialing program requirements match current practice. METHODS: Subject
matter experts from the United States and Canada, representing a broad range of
experiences and perspectives, developed an updated delineation of the domains,
tasks, knowledge, and techniques and tools used in hand therapy practice.
Practicing hand therapists from the United States, Canada, Australia, and 13
other countries reviewed the delineation in a large-scale online survey. RESULTS:
The survey overwhelmingly validated the updated profile. Additionally, the survey
explored trends in hand therapy practice and compared findings with previous
studies. The results were analyzed and compared with findings from previous
studies. CONCLUSION: This analysis led to the revision of the test specifications
for the HTCC; the affirmation of the definition of hand therapy; the refinement
of the scope of hand therapy practice; and guidance for HTCC policy decisions.
LEVEL OF EVIDENCE: Not applicable.
PMID- 27496982
TI - A scoping review of applications and outcomes of traction orthoses and constructs
for the management of intra-articular fractures and fracture dislocations in the
hand.
AB - INTRODUCTION: Intra-articular hand fractures can have devastating consequences
for movement and function. The unique nature of the injury and diverse management
strategies are a challenge for conducting trials. PURPOSE OF THE STUDY: To
conduct a scoping review of traction constructs for the management of intra
articular hand fractures. METHODS: We conducted a systematic search of the
literature, extracting data on the scope and nature of the evidence for traction
constructs. RESULTS: Our search yielded 87 articles addressing 3 traction
constructs: (1) static traction (n = 17), (2) dynamic external fixation (n = 53),
and (3) dynamic orthoses (n = 17). Active range of motion of the target joint was
the most frequently reported outcome. Study designs included 36 cohorts, 21 case
series, and 9 case studies: 24% contained only technical information.
CONCLUSIONS: The current literature addressing traction constructs consists
primarily of small and low-quality studies. Evidence synthesis could improve the
estimation of range of motion outcomes but would not be able to identify the best
treatment. Consensus on classification of fracture patterns, routine use of
outcome measures, and randomized trials are needed to compare different traction
constructs and inform evidence-based care. STUDY DESIGN: Scoping review. LEVEL OF
EVIDENCE: N/A.
PMID- 27496984
TI - Adherence behavior in an acute pediatric hand trauma population: A pilot study of
parental report of adherence levels and influencing factors.
AB - INTRODUCTION: Descriptive and cross-sectional study. PURPOSE OF THE STUDY: The
hand is a common site of injury in children; however, little is known regarding
adherence to hand trauma management in this population. PURPOSE: This pilot study
aimed to describe adherence to plaster slab immobilization, advice regarding
return to sport, appointment attendance, and the factors influencing
nonadherence. METHOD: Forty-seven parents of children with hand trauma completed
an online questionnaire reporting their child's adherence to the initial medical
management. RESULTS: Parents reported that 34% (16 of 47) of children were
adherent to all aspects of management. Nonadherence with plaster slab
immobilization was reported by 38% (18 of 47), and 45% (21 of 47) reported
nonadherence with advice regarding return to sport. Hygiene, discomfort, and
restriction were the most common reasons for plaster removal. Belief that sport
would not cause harm and social factors influenced return to sport against
medical advice. CONCLUSION: Nonadherence behavior is commonly reported in
children with acute hand trauma. LEVEL OF EVIDENCE: 4.
PMID- 27496983
TI - Reproducibility: Reliability and agreement of short version of Western Ontario
Rotator Cuff Index (Short-WORC) in patients with rotator cuff disorders.
AB - INTRODUCTION: Recently, a shorter version of Western Ontario Rotator Cuff Index
(Short-WORC) was proposed as a subset of 7 items from the original 21-item WORC.
However, the reproducibility of the Short-WORC has not been established. PURPOSE
OF THE STUDY: To determine reproducibility (reliability and agreement) of the
Short-WORC among patients with rotator cuff disorders (RCDs). METHODS: Patients
(n = 153) diagnosed with RCD completed the WORC at baseline and at 3 months post
operatively (n = 146). The Short-WORC was extracted from the full version of
WORC. From this retrospective cohort, 43 patients were retested within 5 weeks,
if they remained stable. Cronbach's alpha (alpha) and intra class correlation
coefficients (ICC2,1) were used to assess internal consistency and test-retest
reliability respectively. Standard error measurement (SEM), minimal detectable
change (MDC90) and Bland Altman (BA) plots were used to assess agreement.
RESULTS: No floor and ceiling effects were reported for either the Short-WORC or
WORC. Cronbach's alpha were 0.84 and 0.90 at baseline and 0.89 and 0.95 at 3
month of follow up for Short-WORC and WORC respectively. The ICC2,1 were 0.89 and
0.91 for the Short-WORC and WORC respectively. The agreement parameters for the
Short-WORC were: SEMagreement = 8.8, MDC90individual = 20.3, MDC90group = 5.1. We
found substantial agreement between the two versions of WORC on BA plots with
minimal (mean difference (d) <1) systematic differences between them. The limits
of agreement (LOA) between two versions of WORC were similar across sessions and
fell within range of -11.7 to 13.2 points at test and -14.7 to 14.7 points at
retest. CONCLUSION: Short-WORC and WORC demonstrates strong reproducibility and
can be used for group and individual comparison of health-related quality of life
(HRQoL) among patients with RCD. Wider LOA may be expected when using the Short
WORC for individual patient assessment. Reproducibility data is essential, but
should be supplemented by validation of actual Short-WORC with samples
representing the spectrum of RCD. LEVEL OF EVIDENCE: N/A.
PMID- 27496985
TI - The effectiveness of orthoses in the conservative management of thumb CMC joint
osteoarthritis: An analysis of functional pinch strength.
AB - STUDY DESIGN: The study was a retrospective cohort analysis for a 19-month period
from May 2013 to December 2014. INTRODUCTION: Although the use of orthoses has
long been a staple of conservative treatment measures for individuals with
osteoarthritis of the thumb carpometacarpal (CMC) joint, there remains little
evidence exploring its effectiveness in improving functional outcomes for this
client population. PURPOSE OF THE STUDY: The purpose of this study was to assess
the effectiveness of 3 frequently used orthoses in improving the functional pinch
strength of adults with a diagnosis of thumb CMC joint osteoarthritis. METHODS: A
retrospective cohort analysis was conducted to determine whether pinch strength
improved after orthotic fabrication, and fitting in patients referred to a hand
therapy clinic. RESULTS: Patients who received a Colditz design orthosis had a
mean increase of 2.64 lb with regard to functional pinch strength after orthotic
fabrication and fitting. Patients who received a Comfort Cool orthosis (North
Coast Medical, Morgan Hill, CA) had a mean increase of 2.47 lb, whereas patients
who received a Thumb Spica orthosis had a mean increase of 3.25 lb. There was no
evidence of any statistically significant difference in the average improvements
in pinch strength between the Colditz design orthosis and the Comfort Cool
orthosis. CONCLUSIONS: Results from this study demonstrate that orthosis wear
consistently increases the functional pinch strength of individuals with thumb
CMC joint osteoarthritis. Large-scale multisite research studies comparing
various orthotic designs are necessary to help therapists determine best practice
interventions for the conservative management of thumb CMC joint osteoarthritis.
LEVEL OF EVIDENCE: 2(c).
PMID- 27496986
TI - Coaching of patients with an isolated minimally displaced fracture of the radial
head immediately increases range of motion.
AB - STUDY DESIGN: Prospective cohort. INTRODUCTION: Elbow stiffness is the most
common adverse event after isolated radial head fractures. PURPOSE OF THE STUDY:
To assess the effect of coaching on elbow motion during the same office visit in
patients with such fractures. METHODS: We enrolled 49 adult patients with
minimally displaced radial head fractures, within 14 days of injury. After
diagnosis, we measured demographics, catastrophic thinking, health anxiety,
symptoms of depression, upper extremity-specific symptoms and disability, pain,
and elbow and wrist motion. The patient was taught to apply an effective stretch
in spite of the pain to limit stiffness, and elbow motion was measured again.
RESULTS: With the exception of radial deviation and pronation, motion measures
improved slightly but significantly on average immediately after coaching. Elbow
flexion improved from 79% (110 degrees +/- 22 degrees ) of the uninjured side to
88% (122 degrees +/- 18 degrees ) after coaching (P < .001); elbow extension
improved from 71% (29 degrees +/- 14 degrees ) to 78% (22 degrees +/- 15
degrees ) (P = .0012). DISCUSSION: Instruction that stretching exercises are
healthy even when painful resulted in immediate improvements in motion.
Prospective studies comparing different strategies for coaching patients
regarding painful stretches might help clarify the optimal approach. LEVEL OF
EVIDENCE: Therapeutic level 4.
PMID- 27496987
TI - Clinical Relevance Commentary in Response to: Coaching of patients with and
isolated minimally displaced fracture of the radial head immediately increases
range of motion.
PMID- 27496988
TI - Case Report: The casting motion to mobilize stiffness technique for
rehabilitation after a crush and degloving injury of the hand.
AB - STUDY DESIGN: Case report. INTRODUCTION: This case report describes the use of
the casting motion to mobilize stiffness (CMMS) technique in the management of a
crush and degloving injury of the hand. The patient was unable to attend multiple
hand therapy sessions due to geographic constraints. The CMMS technique involved
the application of a nonremovable plaster of paris cast that selectively
immobilizes proximal joints in an ideal position while constraining distal joints
to direct desired motion over a long period. This uses active motion only.
Traditional hand therapy techniques or modalities are not used. This treatment
approach was beneficial to the patient as a minimum of 2 appointments per month
were needed to regain functional hand use. PURPOSE OF THE STUDY: To document the
use of the CMMS technique as an effective treatment approach in the management of
a crush and degloving injury of the hand. METHODS: The CMMS technique was applied
to the patient's left (nondominant) hand 8 weeks after injury. The technique's
aim was to improve the 30 degrees flexion deformity of the left wrist and
flexion contractures of the index, middle, and ring fingers with a total active
motion of 0 degrees . Orthotic devices and traditional therapy were applied once
joint stiffness was resolved, and a normal pattern of motion was reinstated.
RESULTS: At 6 months, substantial improvement was noted in wrist as well as
metacarpophalangeal and interphalangeal joints. Total active motion exceeded 170
degrees in all fingers excellent functional outcome resulted as measured with
the upper limb functional index short form-10. The upper limb functional index
increased from 0% to 55% of preinjury status (or capacity) over the 18 months of
therapy. DISCUSSION: Brief immobilization through casting causes certain
functional losses, but these are temporary and reversible. CONCLUSION: Finger
stiffness, edema, and tissue fibrosis were successfully managed with the CMMS
technique without the need for attendance at multiple hand therapy sessions.
LEVEL OF EVIDENCE: Level V.
PMID- 27496989
TI - An alternative fabrication method of the dart thrower's motion orthosis (also
known as the dart orthosis).
AB - To allow safe early wrist motion after wrist injury, this author has modified an
earlier version of a dart thrower's motion orthotic device using material that is
currently available on the market and an inexpensive paper fastener as the rivet.
- KristinValdes, OTD, OT, CHT, Practice Forum Editor.
PMID- 27496990
TI - The challenge of the mallet orthosis: A simple solution.
AB - This author provides instruction regarding an alternative, simple, and custom
made orthotic device to manage the mallet finger that may stay in place more
securely while also allowing for proximal interphalangeal joint flexion during
the healing of the terminal tendon. - KristinValdes, OTD, OT, CHT, Practice Forum
Editor, Journal of Hand Therapy.
PMID- 27496991
TI - Mallet finger injuries-A new method to maintain distal interphalangeal joint
extension.
AB - Ensuring that distal interphalangeal joint extension is maintained is an
important but challenging part of the treatment process. These authors describe a
simple approach to ensuring distal interphalangeal joint extension for these
patients. - VictoriaPriganc, PhD, OTR, CHT, CLT, Practice Forum Editor.
PMID- 27496992
TI - Online coupling of high-resolution chromatography with extreme UV photon
activation tandem mass spectrometry: Application to the structural investigation
of complex glycans by dissociative photoionization.
AB - The activation of ions by extreme-energy photons (XUV) produced by a synchrotron
radiation beamline is a powerful method for characterizing complex glycans using
tandem mass spectrometry (MS). As previously described, this activation method
leads to rich fragmentation spectra with many structurally valuable cross-ring
cleavages while maintaining labile modifications on the glycan structures.
However, until now, the tandem MS event was too long to be compatible with liquid
chromatography elution times. In this work, the duty cycle of the activation and
detection of fragments was shortened, and the background signal on the spectra
was drastically reduced. Both improvements allowed, for the first time, the
successful coupling of a UHPLC system to XUV-activated tandem MS. The approach
was used to characterize a complex mixture of oligo-porphyrans, which are a class
of highly sulfated oligosaccharides, in a fully automated way. Due to an enhanced
dynamic range and an increased sensitivity, some hypothetical structures of low
abundance have been unequivocally confirmed in this study and others have been
revised. Some previously undescribed species of oligo-porphyrans that exhibit
lateral branching have been fully resolved. This work contributes to the scarce
knowledge of the structure of porphyrans in red algae and pushes the current
capacities of XUV-activation tandem MS by demonstrating the possibility of a
direct coupling with UHPLC. This study will considerably broaden the
applicability and practicality of this method in many fields of analytical
biology.
PMID- 27496993
TI - Advances in the determination of hindered amine light stabilizers - A review.
AB - Within this paper we discuss analytical strategies for the characterization and
quantitation of hindered amine light stabilizers (HALS) an important sub-group of
polymer additives. For the determination of monomeric HALS a range of mature and
reliable techniques exists, allowing their determination in polymer extracts. If
qualitative or semi-quantitative information suffices, certain techniques are
capable of sampling directly from the polymer surface with limited or no sample
preparation. Different strategies for the determination of complex oligomeric
HALS in extracts from polymer samples are discussed. Here, approaches providing
only a sum parameter including all HALS oligomers have been distinguished from
more sophisticated technologies allowing the determination of single oligomers,
their degradation and by-products. Particularly, the latter issue is facing
increased interest as it provides important information for polymers aging
studies. A tabulated overview provides comprehensive information on different
analytical techniques suitable for HALS determination.
PMID- 27496994
TI - Recent applications of capillary electromigration methods to separation and
analysis of proteins.
AB - This review article describes the significant recent developments in analysis of
proteins by capillary electromigration (CE) methods (zone electrophoresis,
isotachophoresis, isoelectric focusing, affinity electrophoresis, electrokinetic
chromatography and electrochromatography) during the period 2011-2015.
Improvements in sample preparation, preconcentration, suppression of adsorption
and control of electroosmotic flow, separations by particular CE methods, and the
detection schemes used in the analysis of proteins are discussed. Innovative
applications of the above CE methods for quality control of protein
biopharmaceuticals, protein determination in complex biomatrices, peptide mapping
of proteins, and determination of physicochemical parameters of proteins are
presented.
PMID- 27496995
TI - A new and consistent parameter for measuring the quality of multivariate
analytical methods: Generalized analytical sensitivity.
AB - Generalized analytical sensitivity (gamma) is proposed as a new figure of merit,
which can be estimated from a multivariate calibration data set. It can be
confidently applied to compare different calibration methodologies, and helps to
solve literature inconsistencies on the relationship between classical
sensitivity and prediction error. In contrast to the classical plain sensitivity,
gamma incorporates the noise properties in its definition, and its inverse is
well correlated with root mean square errors of prediction in the presence of
general noise structures. The proposal is supported by studying simulated and
experimental first-order multivariate calibration systems with various models,
namely multiple linear regression, principal component regression (PCR) and
maximum likelihood PCR (MLPCR). The simulations included instrumental noise of
different types: independently and identically distributed (iid), correlated
(pink) and proportional noise, while the experimental data carried noise which is
clearly non-iid.
PMID- 27496996
TI - Regression models based on new local strategies for near infrared spectroscopic
data.
AB - In this work, a comparative study of two novel algorithms to perform sample
selection in local regression based on Partial Least Squares Regression (PLS) is
presented. These methodologies were applied for Near Infrared Spectroscopy (NIRS)
quantification of five major constituents in corn seeds and are compared and
contrasted with global PLS calibrations. Validation results show a significant
improvement in the prediction quality when local models implemented by the
proposed algorithms are applied to large data bases.
PMID- 27496997
TI - Electrodeposition of tantalum on carbon black in non-aqueous solution and its
electrocatalytic properties.
AB - In this work, we synthesized tantalum (Ta) nanoclusters on carbon black (Ta/CB)
via simple electrodeposition in non-aqueous solvent, acetonitrile (ACN) at
ambient temperature. Transmission electron microscopy (TEM) images showed that
the electrodeposited Ta nanoclusters consisted of tiny Ta nanoparticles. X-ray
photoelectron spectroscopy (XPS) result represented that the outermost Ta formed
the native oxide on Ta/CB due to its ambient exposure to air. Electrochemical
catalytic properties of prepared Ta/CB on glassy carbon electrode (Ta/CB/GC) were
investigated toward reductions of oxygen and hydrogen peroxide, and oxidations of
ascorbic acid and dopamine. For oxygen reduction reaction (ORR) in acid, Ta/CB/GC
represented a decent electrocatalytic performance which was better or comparable
to bare Pt. The operational stability in acidic condition was maintained up to
500 repetitive potential cycles presumably due to the protective native Ta oxide
layer. Ta/CB/GC also showed high amperometric sensitivity (4.5 (+/-0.16) mA mM(
1) cm(-2), n = 5) for reduction of hydrogen peroxide in 0.1 M phosphate buffer
solution (PBS, pH 7.4). In addition, Ta/CB/GC was demonstrated for the
possibility of simultaneous detection of ascorbic acid and dopamine using
differential pulse voltammetry (DPV).
PMID- 27496998
TI - A novel nonenzymatic biosensor for evaluation of oxidative stress based on
nanocomposites of graphene blended with CuI.
AB - A high-sensitive nonenzymatic hydrogen peroxide (H2O2) biosensor based on cuprous
iodide and graphene (CuI/Gr) composites has been explored for the detection of
H2O2 released by living cells and monitoring the oxidative stress of cells under
excellular stimulation. The biosensor properties were evaluated by cyclic
voltammetry (CV), electrochemical impedance spectroscopy (EIS), amperometric i-t
curve, and the redox-competition mode of scanning electrochemical microscopy
(SECM). Our observations demonstrate that the CuI/Gr nanocomposites modified
glassy carbon electrode (GCE) exhibits excellent catalytic activity for H2O2 with
relatively low detection limit and a wide linear range from 0.5 MUM to 3 mM.
Moreover, the redox-competition mode of SECM imaging study further illustrates
the improved electrochemical catalytic capability for H2O2 reduction with CuI/Gr
nanocomposites deposited on graphite electrode. Hence, the as-prepared
nonenzymatic H2O2 biosensor could be used to detect H2O2 release from different
kinds of living cells under stimulation while eliminating the interference of
ascorbic acid.
PMID- 27496999
TI - Sensitive electrochemical assaying of DNA methyltransferase activity based on
mimic-hybridization chain reaction amplified strategy.
AB - A mimic-hybridization chain reaction (mimic-HCR) amplified strategy was proposed
for sensitive electrochemically detection of DNA methylation and
methyltransferase (MTase) activity In the presence of methylated DNA, DNA-gold
nanoparticles (DNA-AuNPs) were captured on the electrode by sandwich-type
assembly. It then triggered mimic-HCR of two hairpin probes to produce many long
double-helix chains for numerous hexaammineruthenium (III) chloride
([Ru(NH3)6](3+), RuHex) inserting. As a result, the signal for electrochemically
detection of DNA MTase activity could be amplified. If DNA was non-methylated,
however, the sandwich-type assembly would not form because the short double
stranded DNAs (dsDNA) on the Au electrode could be cleaved and digested by
restriction endonuclease HpaII (HapII) and exonuclease III (Exo III), resulting
in the signal decrement. Based on this, an electrochemical approach for detection
of M.SssI MTase activity with high sensitivity was developed. The linear range
for M.SssI MTase activity was from 0.05 U mL(-1) to 10 U mL(-1), with a detection
limit down to 0.03 U mL(-1). Moreover, this detecting strategy held great promise
as an easy-to-use and highly sensitive method for other MTase activity and
inhibition detection by exchanging the corresponding DNA sequence.
PMID- 27497000
TI - A novel reagentless glutamate microband biosensor for real-time cell toxicity
monitoring.
AB - A reagentless glutamate biosensor was applied to the determination of glutamate
released from liver hepatocellular carcinoma cells (HepG2) in response to toxic
challenge from various concentrations of paracetamol. A screen printed carbon
electrode (SPCE) containing the electrocatalyst Meldola's Blue (MB-SPCE) served
as the electron mediator for the oxidation of NADH. A mixture of the enzyme
glutamate dehydrogenase (GLDH), cofactor nicotinamide adenine dinucleotide
(NAD(+)) and the biopolymer chitosan (CHIT) were drop-coated onto the surface of
the transducer (MB-SPCE) in a simple one step fabrication process. The
reagentless biosensor was used with amperometry in stirred solution at an applied
potential of +0.1 V (vs. Ag/AgCl). All experiments were carried out at the
following conditions: pH 7, temperature 37 degrees C, atmosphere 5% CO2. The
linear range of the device was found to be 25-125 MUM in phosphate buffer (75 mM,
containing 0.05 M NaCl) and 25-150 MUM in cell culture medium. The limits of
detection (LOD) were found to be 1.2 MUM and 4.2 MUM based on three times signal
to noise, using PBS and culture medium respectively. The sensitivity was
calculated to be 106 nA MUM(-1) cm(-2) and 210 nA MUM(-1) cm(-2) in PBS and cell
medium respectively. The response time was ~60 s in an agitated solution. HepG2
cells were exposed to various concentrations of paracetamol (1 mM, 5 mM and 10
mM) in order to investigate the drug-induced release of glutamate into the
culture medium in real time. Two toxicity studies were investigated using
different methods of exposure and analysis. The first method consisted of a
single measurement of the glutamate concentration, using the method of standard
addition, after 24 h incubation. The concentrations of glutamate were found to be
52 MUM, 93 MUM and 177 MUM, released on exposure to 1 mM, 5 mM and 10 mM
paracetamol respectively. The second method involved the continuous monitoring of
glutamate released from HepG2 cells upon exposure to paracetamol over 8 h. The
concentrations of glutamate released in the presence of 1 mM, 5 mM and 10 mM
paracetamol, increased in proportion to the drug concentration, ie: 16 MUM, 28
MUM and 62 MUM respectively. This result demonstrates the feasibility of using
this approach to monitor early metabolic changes after exposure to a model toxic
compound.
PMID- 27497001
TI - Enzymatic biosensor of horseradish peroxidase immobilized on Au-Pt nanotube/Au
graphene for the simultaneous determination of antioxidants.
AB - A new electrochemical method has been proposed for the simultaneous determination
of butylated hydroxyanisole (BHA) and propyl gallate (PG) in food matrices based
on enzymatic biosensors. Spiny Au-Pt nanotubes (SAP NTs) was first synthesized
and demonstrated to exhibit intrinsic peroxidase and catalase-like activity. The
structure of SAP NTs provides large surface area and favorable medium for
electron transfer, on which HRP were immobilized and acted as enzymatic biosensor
for the simultaneous detection of BHA and PG. The results revealed that BHA and
PG both have well-defined oxidation waves with peak potentials of 624 and 655 mV,
respectively. Under the optimal conditions, the method behaved satisfactory
analytical performance towards BHA and PG with a wide linear range of 0.3-50 mg
L(-1) and 0.1-100 mg L(-1), as well as a detection limit of 0.046 mg L(-1) and
0.024 mg L(-1) (3sigma/slope), respectively. Besides, the proposed method
exhibits good sensitivity, stability and reproducibility, providing an
alternative to fabricate electrode and construct sensitive biosensors.
PMID- 27497002
TI - C18-attached membrane funnel-based spray ionization mass spectrometry for
quantification of anti-diabetic drug from human plasma.
AB - In this work, sorbent-attached membrane funnel-based spray ionization mass
spectrometry was explored for quantitative analysis of anti-diabetic drugs spiked
in human plasma. C18-attached membrane funnel was fabricated for in situ
extraction and clean-up to alleviate matrix suppression effect in the ionization
process. Repaglinide was used as a target analyte of anti-diabetic drugs. Under
optimal working conditions, good linearity (R(2) > 0.99) was obtained in the
concentration range of 1-100 ng mL(-1). The method detection limit of target
drugs spiked in the human plasma was around 0.30 ng mL(-1). Through the
application of an isotope-labeled internal standard, the signal fluctuation
caused by residual background matrices was largely alleviated and the precision
of measurement (RSD) was below 15%. The recovery of repaglinide for 5, 25, and
100 ng mL(-1) of spiked human plasma matrixes ranged from 87% to 112%. The
developed method was successfully applied to determine repaglinide in plasma
volunteers who orally received a dose of drug association. Our results
demonstrated that membrane funnel-based spray is a simple and sensitive method
for rapid screening analysis of complex biological samples.
PMID- 27497003
TI - Development of the HS-SPME-GC-MS/MS method for analysis of chemical warfare agent
and their degradation products in environmental samples.
AB - After World War II approximately 50,000 tons of chemical weapons were dumped in
the Baltic Sea by the Soviet Union under the provisions of the Potsdam Conference
on Disarmament. These dumped chemical warfare agents still possess a major threat
to the marine environment and to human life. Therefore, continue monitoring of
these munitions is essential. In this work, we present the application of new
solid phase microextraction fibers in analysis of chemical warfare agents and
their degradation products. It can be concluded that the best fiber for analysis
of sulfur mustard and its degradation products is butyl acrylate (BA), whereas
for analysis of organoarsenic compounds and chloroacetophenone, the best fiber is
a co-polymer of methyl acrylate and methyl methacrylate (MA/MMA). In order to
achieve the lowest LOD and LOQ the samples should be divided into two subsamples.
One of them should be analyzed using a BA fiber, and the second one using a
MA/MMA fiber. When the fast analysis is required, the microextraction should be
performed by use of a butyl acrylate fiber because the extraction efficiency of
organoarsenic compounds for this fiber is acceptable. Next, we have elaborated of
the HS-SPME-GC-MS/MS method for analysis of CWA degradation products in
environmental samples using laboratory obtained fibers The analytical method for
analysis of organosulfur and organoarsenic compounds was optimized and validated.
The LOD's for all target chemicals were between 0.03 and 0.65 ppb. Then, the
analytical method developed by us, was used for the analysis of sediment and pore
water samples from the Baltic Sea. During these studies, 80 samples were
analyzed. It was found that 25 sediments and 5 pore water samples contained CWA
degradation products such as 1,4-dithiane, 1,4-oxathiane or triphenylarsine, the
latter being a component of arsine oil. The obtained data is evidence that the
CWAs present in the Baltic Sea have leaked into the general marine environment.
PMID- 27497004
TI - Calibration of the complex matrix effects on the sampling of polycyclic aromatic
hydrocarbons in milk samples using solid phase microextraction.
AB - Solid phase microextraction (SPME), a simple, fast and promising sampling
technique, has been widely used for complex sample analysis. However, complex
matrices could modify the absorption property of coatings as well as the uptake
kinetics of analytes, eventually biasing the quantification results. In the
current study, we demonstrated the feasibility of a developed calibration method
for the analysis of polycyclic aromatic hydrocarbons (PAHs) in complex milk
samples. Effects of the complex matrices on the SPME sampling process and the
sampling conditions were investigated. Results showed that short exposure time
(pre-equilibrium SPME, PE-SPME) could increase the lifetime of coatings, and the
complex matrices in milk samples could significantly influence the sampling
kinetics of SPME. In addition, the optimized sampling time, temperature and
dilution factor for PAHs were 10 min, 85 degrees C and 20, respectively. The
obtained LODs and LOQs of all the PAHs were 0.1-0.8 ng/mL and 1.4-4.7 ng/mL,
respectively. Furthermore, the accuracy of the proposed PE-SPME method for milk
sampling was validated by the recoveries of the studied compounds in two
concentration levels, which ranged from 75% to 110% for all the compounds.
Finally, the proposed method was applied to the screening of PAHs in milk
samples.
PMID- 27497005
TI - Evaluation of in vivo solid phase microextraction for minimally invasive analysis
of nonvolatile phytochemicals in Amazonian plants.
AB - INTRODUCTION: Although solid phase microextraction (SPME) has been used
extensively for fingerprinting volatile compounds emitted by plants, there are
very few such reports for direct insertion SPME. In this research, direct contact
of SPME probes with the interstitial fluid of plants was investigated as a method
for phytochemical analysis. OBJECTIVE: Medicinal plants from the Amazon have been
the source of numerous drugs used in western medicine. However, a large number of
species used in traditional medicine have not been characterized chemically,
partly due to the difficulty of field work. In this project, the phytochemical
composition of plants from several genera was fingerprinted by combining
convenient field sampling by solid phase microextraction (SPME) with laboratory
analysis by LC-MS. The new method was compared with classical sampling followed
by liquid extraction (LE). METHODOLOGY: SPME probes were prepared by coating
stainless steel wires with a mixture of polyacrylonitrile and either RP-amide or
HS-F5 silica particles. Sampling was performed by inserting the microextraction
probes into various tissues of living plants in their natural environment. After
in vivo extraction, the probes were sealed under vacuum and refrigerated until
analyzed. The probes were desorbed in mobile phase and analyzed on a Waters
Acquity UPLC with triple quadrupole mass spectrometer in positive ion mode.
RESULTS: Twenty Amazonian plant species were sampled and unique metabolomic
fingerprints were obtained. In addition, quantitative analysis was performed for
previously identified compounds in three species. Comparison of the fingerprints
obtained by in vivo SPME with those obtained by LE showed that 27% of the
chromatographic features were unique to SPME, 57% were unique to LE, and 16% were
common to both methods. CONCLUSION: In vivo SPME caused minimal damage to the
plants, was much faster than traditional liquid extraction, and provided unique
fingerprints for all investigated plants. SPME revealed unique chromatographic
features, undetected by traditional extraction, although it produced only half as
many peaks as ethanol extraction.
PMID- 27497006
TI - Effective methylation of phosphonic acids related to chemical warfare agents
mediated by trimethyloxonium tetrafluoroborate for their qualitative detection
and identification by gas chromatography-mass spectrometry.
AB - The effective methylation of phosphonic acids related to chemical warfare agents
(CWAs) employing trimethyloxonium tetrafluoroborate (TMO.BF4) for their
qualitative detection and identification by gas chromatography-mass spectrometry
(GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be
conveniently carried out at ambient temperature, thus providing a safer
alternative to the universally employed diazomethane-based methylation protocols.
Optimization of the methylation parameters led us to conclude that methylene
chloride was the ideal solvent to carry out the derivatization, and that even
though methylated products can be observed surfacing after only 1 h, additional
time was not found to be detrimental but beneficial to the process particularly
when dealing with analytes at low concentrations (~10 MUg mL(-1)). Due to its
insolubility in methylene chloride, TMO.BF4 conveniently settles to the bottom
during the reaction and does not produce additional interfering by-products that
may further complicate the GC-MS analysis. The method was demonstrated to
successfully methylate a variety of Schedule 2 phosphonic acids, including their
half esters, resulting in derivatives that were readily detected and identified
using the instrument's spectral library. Most importantly, the method was shown
to simultaneously methylate a mixture of the organophosphorus-based nerve agent
hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl
methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 MUg mL(-1)
concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O3)
featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW)
Proficiency Test. In addition, the protocol was found to effectively methylate
N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid
that are products arising from the oxidative degradation of the V-series agents
VR and VX respectively. The work described herein represents the first report on
the use of TMO.BF4 as a viable, stable and safe agent for the methylation of
phosphonic acids and their half esters and within the context of an OPCW
Proficiency Test sample analysis.
PMID- 27497007
TI - Quantitative analysis of wild-type and V600E mutant BRAF proteins in colorectal
carcinoma using immunoenrichment and targeted mass spectrometry.
AB - The BRAF V600E mutation is one of the most common mutations implicated in the
development of several types of cancer including colorectal cancer (CRC), where
it is associated with aggressive disease phenotypes and poor outcomes. The status
of the BRAF V600E mutation is frequently determined by direct DNA sequencing.
However, no previous study has sought to quantify the BRAF V600E protein in
cancer specimens. Here, we evaluated immunoenrichment coupled with two MS-based
quantitative techniques, namely multiple reaction monitoring (MRM) and single ion
monitoring conjugated accurate inclusion mass screening (SIM-AIMS), to detect and
precisely quantify wild-type (WT) and V600E mutant BRAF proteins in DNA sequence
confirmed CRC tissue specimens. WT and V600E BRAF proteins were
immunoprecipitated from a CRC cell line (HT-29), and their representative
peptides ((592)IGDFGLATVK(601) and (592)IGDFGLATEK(601), respectively) were
confirmed by LC-MS/MS analysis and then quantified by MRM or SIM-AIMS with spiked
stable isotope-labeled peptide standards. Both assays worked well for measuring
WT BRAF from different amounts of HT-29 cell lysates, but the MRM assay was more
sensitive than SIM-AIMS assay for quantifying lower levels of V600E BRAF. In
protein extracts (2 mg) from 11 CRC tissue specimens, the MRM assay could measure
WT BRAF in all 11 cases (0.32-1.66 ng) and the V600E BRAF in two cases (0.1-0.13
ng; mutant-to-WT ratio, 0.16-0.17). The SIM-AIMS assay could also detect WT and
V600E BRAF in CRC specimens, but the measured levels of both targets were lower
than those determined by MRM assay. Collectively, this study provides an
effective method to precisely quantify WT and V600E BRAF proteins in complex
biological samples using immunoenrichment-coupled targeted MS. Since the V600E
BRAF protein has emerged as an important therapeutic target for cancer, the
developed assay should facilitate future BRAF-related basic and clinical studies.
PMID- 27497008
TI - An integrated electrophoretic mobility control device with split design for
signal improvement in liquid chromatography-electrospray ionization mass
spectrometry analysis of aminoglycosides using a heptafluorobutyric acid
containing mobile phase.
AB - Electrophoretic mobility control (EMC) was used to alleviate the adverse effect
of the ion-pairing agent heptafluorobutyric acid (HFBA) in the liquid
chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis of
aminoglycosides. Aminoglycosides separated by LC were directed to a connecting
column before their detection via ESI. Applying an electric field across the
connecting column caused the positively charged aminoglycosides to migrate toward
the mass spectrometer whereas the HFBA anions remained in the junction reservoir,
thus alleviating the ion suppression caused by HFBA. To accommodate the flow rate
of a narrow-bore column, minimize the effect of electrophoretic mobility on
separation, and facilitate the operation, an integrated EMC device with a split
design was fabricated. With the proposed EMC device, the signals of
aminoglycosides were enhanced by a factor of 5-85 without affecting the
separation efficiency or elution order. For the analysis of aminoglycosides in
bovine milk, the proposed approach demonstrates a sensitivity that is at least 10
times below the maximum residue limits set by most countries.
PMID- 27497009
TI - Analysis of a series of chlorogenic acid isomers using differential ion mobility
and tandem mass spectrometry.
AB - Chlorogenic acids are among the most abundant phenolics found in the human diet.
Of these, the mono-caffeoylquinic acids are the predominant phenolics found in
fruits, such as apples and pears, and products derived from them. In this
research, a comprehensive study of the electrospray ionization (ESI) tandem mass
spectrometric (MS/MS) dissociation behavior of the three most common mono
caffeoylquinic acids, namely 5-O-caffeoylquinic acid (5-CQA), 3-O-caffeoylquinic
acid (3-CQA) and 4-O-caffeoylquinic acid (4-CQA), were determined using both
positive and negative ionization. All proposed structures of the observed product
ions were confirmed with second-generation MS(3) experiments. Similarities and
differences between the dissociation pathways in the positive and negative ion
modes are discussed, confirming the proposed structures and the established MS/MS
fingerprints. MS/MS dissociation was primarily driven via the cleavage of the
ester bond linking the quinic acid moiety to the caffeic acid moiety within
tested molecules. Despite being structural isomers with the same m/z values and
dissociation behaviors, the MS/MS data in the negative ion mode was able to
differentiate the three isomers based on ion intensity for the major product
ions, observed at m/z 191, 179 and 173. This differentiation was consistent among
various MS instruments. In addition, ESI coupled with high-field asymmetric
waveform ion mobility spectrometry-mass spectrometry (ESI-FAIMS-MS) was employed
for the separation of these compounds for the first time. By combining MS/MS data
and differential ion mobility, a method for the separation and identification of
mono-caffeoylquinic in apple/pear juice samples was developed with a run time of
less than 1 min. It is envisaged that this methodology could be used to identify
pure juices based on their chlorogenic acid profile (i.e., metabolomics), and
could also be used to detect juice-to-juice adulteration (e.g., apple juice
addition to pear juice).
PMID- 27497010
TI - Distinguishing normal cells from cancer cells via lysosome-targetable pH
biomarkers with benzo[a]phenoxazine skeleton.
AB - In this paper, the design of a lysosome-targetable pH probe that has a
fluorescent OFF (pH = 4) to ON (pH = 5-6) response is described to identify
lysosomes in normal cells. The mechanism of photoinduced electron transfer with a
fluorophore-based reaction (FBR-PET) was proposed. Benzo[a]phenoxazines with
electro-donating aryl groups were selected, its (2,5-dimethoxyphenyl)imino-, (2
hydroxyphenyl)imino- and (2-hydroxy-5-methoxyphenyl)- imino-derivatives (probes
1a-c) were prepared and their optical responses towards pH were evaluated; their
fluorescence pH titration experiments gave regularly changes with the increasing
electro-donating abilities at the linked aryl groups, the (2-hydroxy-5
methoxyphenyl)iminobenzo[a]phenoxazine (probe 1c) exhibited a nearly OFF-ON
response at 580-800 nm. All probes were reversible, and they showed excellent
selectivity toward the proton over other competitive species. Fluorescence
confocal images were performed with HeLa, KB cancer cells and V79 normal cells,
probes 1a-c are all lysosome-targetable pH probes, and benzo[a]phenoxazine with
(2-hydroxy-5-methoxyphenyl)imino-group (probe 1c) has potential applications in
selective differentiation of normal cells from cancer cells.
PMID- 27497011
TI - Reusable split-aptamer-based biosensor for rapid detection of cocaine in serum by
using an all-fiber evanescent wave optical biosensing platform.
AB - A rapid, facile, and sensitive assay of cocaine in biological fluids is important
to prevent illegal abuse of drugs. A two-step structure-switching aptasensor has
been developed for cocaine detection based on evanescent wave optical biosensing
platform. In the proposed biosensing platform, two tailored aptamer probes were
used to construct the molecular structure switching. In the existence of cocaine,
two fragments of cocaine aptamer formed a three-way junction quickly, and the
fluorophore group of one fragment was effectively quenched by the quencher group
of the other one. The tail of the three-way junction hybridized with the cDNA
sequences immobilized on the optical fiber biosensor. Fluorescence was excited by
evanescent wave, and the fluorescence signal was proportional to cocaine
concentration. Cocaine was detected in 450 s (300 s for incubation and 150 s for
detection and regeneration) with a limit of detection (LOD) of 165.2 nM. The
proposed aptasensor was evaluated in human serum samples, and it exhibited good
recovery, precision, and accuracy without complicated sample pretreatments.
PMID- 27497012
TI - A TPA-caged precursor of (imino)coumarin for "turn-on" fluorogenic detection of
Cu(.).
AB - We strategize to utilize the precursors of (imino)coumarin fluorophores to
deliver novel reactive Cu(+) probes, where tris[(2-pyridyl)-methyl] amine (TPA)
works as a reactive receptor towards Cu(+). To verify this strategy, CP1, a
representative probe and relevant sensing behaviors towards Cu(+) are presented
here. CP1 features good solubility and fast response for monitoring labile copper
in aqueous solution and live cells. The sensing mechanism of CP1 is determined by
HPLC titration and mass spectrometric analysis. The probe CP1 exhibits a 60-fold
fluorescence enhancement and a detection limitation of 10.8 nM upon the detection
of Cu(+). CP1 is further applied for imaging labile copper in live cells. This
work provides a starting point for future development of Cu(+) probes, based on
in situ formation of (imino)coumarin scaffolds, as well as their further
investigations of copper signaling and biological events.
PMID- 27497013
TI - Plasmonic-based colorimetric and spectroscopic discrimination of acetic and
butyric acids produced by different types of Escherichia coli through the
different assembly structures formation of gold nanoparticles.
AB - We present a plasmonic-based strategy for the colourimetric and spectroscopic
differentiation of various organic acids produced by bacteria. The strategy is
based on our discovery that particular concentrations of dl-lactic, acetic, and
butyric acids induce different assembly structures, colours, and optical spectra
of gold nanoparticles. We selected wild-type (K-12 W3110) and genetically
engineered (JHL61) Escherichia coli (E. coli) that are known to primarily produce
acetic and butyric acid, respectively. Different assembly structures and optical
properties of gold nanoparticles were observed when different organic acids,
obtained after the removal of acid-producing bacteria, were mixed with gold
nanoparticles. Moreover, at moderate cell concentrations of K-12 W3110 E. coli,
which produce sufficient amounts of acetic acid to induce the assembly of gold
nanoparticles, a direct estimate of the number of bacteria was possible based on
time-course colour change observations of gold nanoparticle aqueous suspensions.
The plasmonic-based colourimetric and spectroscopic methods described here may
enable onsite testing for the identification of organic acids produced by
bacteria and the estimation of bacterial numbers, which have applications in
health and environmental sciences.
PMID- 27497014
TI - Integrating Palliative Care into Primary Care.
AB - Improved quality of life, care consistent with patient goals of care, and
decreased health care spending are benefits of palliative care. Palliative care
is appropriate for anyone with a serious illness. Advances in technology and
pharmaceuticals have resulted in increasing numbers of seriously ill individuals,
many with a high symptom burden. The numbers of individuals who could benefit
from palliative care far outweighs the number of palliative care specialists. To
integrate palliative care into primary care it is essential that resources are
available to improve generalist palliative care skills, identify appropriate
patients and refer complex patients to specialist palliative care providers.
PMID- 27497015
TI - Animal-Assisted Therapy in Pediatric Palliative Care.
AB - Animal-assisted therapy is an emerging complementary strategy with an increasing
presence in the literature. Limited studies have been conducted with children,
particularly those with life-threatening and life-limiting conditions. Although
outcomes show promise in decreasing suffering of children receiving palliative
care services, more work is needed to validate evidence to support implementation
of animal-assisted therapy with this vulnerable population.
PMID- 27497017
TI - Pain Management in the Individual with Serious Illness and Comorbid Substance Use
Disorder.
AB - Pain is a common occurrence in individuals with serious illnesses. Effective pain
management can be complicated when the individual has a comorbid substance use
disorder. Comprehensive pain assessment includes opioid risk screening to provide
safe and effective pain management. An appropriate, safe treatment plan includes
the use of "universal precautions" commonly used in managing chronic pain.
PMID- 27497018
TI - A Review of Palliative Sedation.
AB - Palliative sedation has become a standard practice to treat refractory symptoms
at end-of-life. Dyspnea and delirium are the two most commonly treated symptoms.
The medications used in palliative sedation are usually benzodiazepines,
barbiturates, antipsychotics, and/or anesthetics. Some ethical considerations
remain, especially surrounding the use of palliative sedation in psychological
distress and existential suffering.
PMID- 27497016
TI - Pain Assessment in Noncommunicative Adult Palliative Care Patients.
AB - Palliative care patients who have pain are often unable to self-report their
pain, placing them at increased risk for underrecognized and undertreated pain.
Use of appropriate pain assessment tools significantly enhances the likelihood of
effective pain management and improved pain-related outcomes. This paper reviews
selected tools and provides palliative care clinicians with a practical approach
to selecting a pain assessment tool for noncommunicative adult patients.
PMID- 27497019
TI - Family Care During End-of-Life Vigils.
AB - An end-of-life vigil is the act of being with another toward death. A family
vigil at end-of-life occurs when significant others gather by the bedside of
dying individuals in the weeks, days, or hours prior to the death event. It is
not unusual for nurses to be present, bear witness, and share in this human
experience. This article reviews seminal and current research regarding the
meaning and structure of the lived experience of vigil keeping for a dying family
member, and translates research to inform nurses regarding family care during the
transition at end-of-life.
PMID- 27497020
TI - Rituals at End-of-Life.
AB - Understanding the significance of rituals at the end-of-life enables health care
professionals to offer meaningful and compassionate interventions that enhance
quality of life and support those dying and those who grieve. Rituals contribute
to the strength, capacity, and health of providers who cope with death events.
Rituals help the living create continuing bonds with those dying, help with
coping skills, and allow healthy growth through opportunities for naming,
honoring, and memorializing. The display of respect and a nonjudgmental attitude
create a space for support, trust, sharing of emotion, empowerment, and quality
of care during end-of-life events.
PMID- 27497021
TI - Seeing the Light: End-of-Life Experiences-Visions, Energy Surges, and Other Death
Bed Phenomena.
AB - Spiritual care is an integral part of multidimensional palliative care and a
major domain of care identified in definitions and guidelines. Death bed
phenomena include visions, dreams, hallucinations, and premortem energy surges,
which can be deeply spiritual experiences. Death bed occurrences are often a
source of consolation. However, they have been underrecognized. The last hours of
life are sacred; as holistic, multidimensional practitioners, nurses should
remain open to experiences not easily explained within a traditional medical
model. As the most consistent caregivers, nurses assess, recognize, and validate
such experiences to assist patients in finding meaning, comfort, and a peaceful
end-of-life.
PMID- 27497022
TI - Providing Palliative Care to LGBTQ Patients.
AB - Nurses should be familiar with and equipped to address the challenges that arise
when caring for lesbian, gay, bisexual, transgender, or queer-identified (LGBTQ)
patients. LGBTQ individuals have increased rates of certain physical diseases and
are at greater risk of suffering from stress-sensitive mental health issues.
Negative social attitudes, widespread discrimination and stigma, physical and
psychological victimization, and less social support with aging contribute to the
complexity of care for these individuals. Open communication, welcoming and
accepting attitudes and environments, and sensitivity to unique multidimensional
issues improve care to LGBTQ patients with serious advanced illness. Nursing can
reach this vulnerable minority and positively impact the quality of care.
PMID- 27497023
TI - Palliative Wound Care for Malignant Fungating Wounds: Holistic Considerations at
End-of-Life.
AB - Timely, holistic interventions aimed at easing the despair of patients with
advanced cancer and malignant fungating wounds (MFWs) must incorporate patient
and family goals of care in all aspects of decision-making. People with MFWs
suffer from a devastating and often crippling symptom burden including
disfigurement, pain, pruritus, malodor, exudates, and bleeding. These symptoms
may lead to psychosocial and/or spiritual distress, isolation, and diminished
quality of life. The complexity of caring for hospice patients with MFWs requires
a pragmatic and holistic interdisciplinary approach guided by specialist-level
palliative wound care. This article introduces a framework to assist clinicians
in the assessment and management of terminally ill patients with MFWs.
PMID- 27497024
TI - The Difference Between Palliative Care and End of Life Care: More than Semantics.
PMID- 27497025
TI - Palliative and End-of-Life Care: Compassion, Care, Commitment, Communication,
Communion.
PMID- 27497026
TI - Revisiting IL-6 antagonism in multiple myeloma.
AB - IL-6, a cytokine with broad functions in inflammation and immunity, has been
extensively studied for its role on normal antibody-producing plasma cells. In
addition, IL-6 is recognized as a proliferative factor for multiple myeloma (MM),
a malignant plasma cell tumor developing in the bone marrow. Blocking IL-6
signaling was thus developed into a therapeutic approach for MM already early
after its discovery, in 1991. Unfortunately, the first clinical trials did not
demonstrate a clear benefit, but despite this apparent failure hopes on IL-6
antagonism are still high and trials ongoing. The cellular source of IL-6 has
long been a matter of debate. IL-6 was first recognized as an autocrine factor
produced by the malignant plasma cells themselves, but later reports clearly
showed that IL-6 was a paracrine factor, produced by the microenvironment, mostly
by cells from the myeloid lineage. Recently, we have confirmed that IL-6
originates from myeloid lineage cells, mainly from myeloid precursors. We have
also demonstrated that IL-6 amplifies the pool of myeloid cells producing a
second key factor for MM, a proliferation inducing ligand (APRIL). These findings
form a new rationale for IL-6 inhibition in MM and for new ways to use IL-6
blocking in the clinics.
PMID- 27497027
TI - Zevalin((r)) (ibritumomab tiuxetan): After more than a decade of treatment
experience, what have we learned?
AB - Non-Hodgkin's lymphoma (NHL) comprises a clinically and biologically
heterogeneous group of lymphoproliferative disorders originating in B
lymphocytes, T lymphocytes, or natural killer (NK) cells. The disease course may
range from indolent to aggressive. Zevalin((r)) (ibritumomab tiuxetan) is a
radioactive drug product, which is the combination of a beta-emitting isotope,
(90)Y, linked to the anti-CD20 monoclonal antibody (mAb), rituximab. It has
demonstrated therapeutic efficacy with durable responses and allows delivery of
ionizing radiation directly to the tumor site, while minimizing toxicity to
normal tissue. Ibritumomab tiuxetan is indicated for treatment of patients with
relapsed or refractory low-grade, follicular NHL, including patients who are
refractory to rituximab, and as consolidation therapy in previously untreated
follicular NHL in patients who achieve a partial or complete response to first
line chemotherapy. Despite the efficacy and acceptable safety profile of
ibritumomab tiuxetan, utilization has not been broadly adopted in practice due to
a number of factors. This manuscript will review the literature available for
ibritumomab tiuxetan, including several new trials that are currently being
studied, and discuss the rationale for use of ibritumomab tiuxetan in NHL.
PMID- 27497028
TI - Oxaliplatin-based chemotherapy combined with traditional medicines for
neutropenia in colorectal cancer: A meta-analysis of the contributions of
specific plants.
AB - This review assessed the effects on chemotherapy induced neutropenia (CIN) of
combining oxaliplatin regimens with traditional plant-based medicines (TMs) in
the management of colorectal cancer (CRC). 32 RCTs (2224 participants) were
included. Meta-analysis showed reduced incidence of grade 3/4 CIN (RR 0.45[0.31,
0.65], I(2)=0%). No studies reported serious adverse events or reduction in
tumour response rates associated with concurrent use of oxaliplatin and TM. Due
to small sample sizes and risk of bias, these results should be interpreted with
caution. Analyses of sub-groups of studies that used similar TM interventions
assessed the relative contributions of individual plant-based ingredients to the
results. Astragalus, Codonopsis, Atractylodes, Poria and Coix, in various
combinations were consistently associated with reduced CIN incidence when
administered orally. Experimental studies of these plants have reported reduced
myelosuppression and/or enhanced immune response. Further studies of these plants
may lead to the development of interventions to supplement conventional CIN
treatment.
PMID- 27497029
TI - The Experiences of Professionals Regarding Involvement of Parents in Neonatal
Pain Management.
AB - OBJECTIVE: To explore the experiences of health care professionals related to
parent involvement during painful procedures carried out on their infants and to
describe contextual facilitators and barriers that influence parent involvement
during evidence-based, nonpharmacologic pain relief. DESIGN: Qualitative study
with focus group interviews. SETTING: Two Level III NICUs and one Level II NICU
in the German-speaking part of Switzerland. PARTICIPANTS: Convenience sample of
17 NICU nurses and six neonatologists. METHODS: Three interprofessional focus
group interviews were conducted. Data were analyzed by thematic analysis.
RESULTS: Contextual factors among professionals, such as know-how and
communication skills regarding neonatal pain management; reflective and
collaborative practice; and an attitude of partnership with parents and
organizational resources, such as time and staffing, promoted a working
atmosphere in which it was possible to talk about neonatal pain with parents.
Within this context, parents could be successfully involved in their infant's
pain management. In contrast, lack of the aforementioned contextual factors,
including an attitude of paternalism toward parents, resulted in a working
atmosphere in which professionals "kept silent about pain" and hindered parent
involvement during painful procedures. CONCLUSION: The work culture and
organizational features of a NICU facilitate or hinder parent involvement in
neonatal pain management. Facilitators and barriers should be identified from the
individual, team, and system perspectives. Facilitation of parent-centered pain
management in infants should be promoted by the organization.
PMID- 27497030
TI - Effect of Parent Presence During Multidisciplinary Rounds on NICU-Related
Parental Stress.
AB - OBJECTIVE: To evaluate the effect of parent presence during multidisciplinary
rounds on NICU-related parental stress. DESIGN: Quasi-experimental study.
SETTING: University-affiliated, 24-bed NICU located within a children's hospital
that admits infants from birth to 6 months of age. PARTICIPANTS: One hundred
thirty-two parents of infants admitted to the NICU for the first time. METHODS:
All parents completed the Parent Stressor Scale: NICU (PSS:NICU) on Study Days 0
and 3. In addition to usual family communication practices, parents in the
experimental group were offered the opportunity to participate in
multidisciplinary rounds on their infants. RESULTS: A total of 132 parents
completed the study; the first 46 parents were enrolled in the control group, and
the subsequent 86 parents in the experimental group. Overall PSS:NICU scores
decreased significantly in the experimental group between Study Days 0 and 3
(mean +/- standard error [SE] = -0.24 +/- 0.07, p < .001), but the change was not
significantly different between the control and experimental groups (mean +/- SE
= -0.12 +/- 0.10, p = .25). The PSS:NICU Parental Role Alteration subscale
decreased by the largest margin in the experimental group (mean +/- SE = -0.42 +/
0.09, p < .0001), but the change was not significantly different between groups
(mean +/- SE = -0.26 +/- 0.14, p = .06). Overall PSS:NICU stress scores were
higher in mothers than fathers (mothers, mean +/- SE = 3.4 +/- 0.81; fathers,
mean +/- SE = 2.7 +/- 0.67; p < .001). CONCLUSION: Providing parents with the
opportunity to participate in multidisciplinary rounds did not affect NICU
related parental stress. Mothers reported higher levels of stress than fathers.
PMID- 27497031
TI - Impact of WRF model PBL schemes on air quality simulations over Catalonia, Spain.
AB - Here we analyze the impact of four planetary boundary-layer (PBL) parametrization
schemes from the Weather Research and Forecasting (WRF) numerical weather
prediction model on simulations of meteorological variables and predicted
pollutant concentrations from an air quality forecast system (AQFS). The current
setup of the Spanish operational AQFS, CALIOPE, is composed of the WRF-ARW V3.5.1
meteorological model tied to the Yonsei University (YSU) PBL scheme, HERMES v2
emissions model, CMAQ V5.0.2 chemical transport model, and dust outputs from BSC
DREAM8bv2. We test the performance of the YSU scheme against the Assymetric
Convective Model Version 2 (ACM2), Mellor-Yamada-Janjic (MYJ), and Bougeault
Lacarrere (BouLac) schemes. The one-day diagnostic case study is selected to
represent the most frequent synoptic condition in the northeast Iberian Peninsula
during spring 2015; regional recirculations. It is shown that the ACM2 PBL scheme
performs well with daytime PBL height, as validated against estimates retrieved
using a micro-pulse lidar system (mean bias=-0.11km). In turn, the BouLac scheme
showed WRF-simulated air and dew point temperature closer to METAR surface
meteorological observations. Results are more ambiguous when simulated pollutant
concentrations from CMAQ are validated against network urban, suburban, and rural
background stations. The ACM2 scheme showed the lowest mean bias (-0.96MUgm-3)
with respect to surface ozone at urban stations, while the YSU scheme performed
best with simulated nitrogen dioxide (-6.48MUgm-3). The poorest results were with
simulated particulate matter, with similar results found with all schemes tested.
PMID- 27497032
TI - The association between ambient temperature and out-of-hospital cardiac arrest in
Guangzhou, China.
AB - Out-of-hospital cardiac arrest (OHCA) is becoming a considerable public health
burden worldwide. The seasonal variation of OHCA has been observed, but the
potential effects of ambient temperature on OHCA were rarely investigated. We,
therefore, aimed to evaluate the association between ambient temperature and OHCA
in Guangzhou, China. We collected daily emergency ambulance dispatches for OHCA
from the Guangzhou Emergency Center from January 1, 2008 to December 31, 2012. We
analyzed the associations using the time-series method. We applied the
generalized linear model combined with the distributed lag non-linear model to
estimate the potentially non-linear and lagged effects of temperature on OHCA.
Time trends, day of the week, and air pollutants were controlled as covariates.
We identified a total of 4369 cases of OHCD. The associations between daily mean
temperature and OHCA were generally J-shaped. Both low and high temperatures
could increase the risk of OHCA. The effects were strongest on the concurrent day
(lag 0) and lasted for 6 or 7days. The cumulative risks of extreme cold (1st
percentile of temperature) and extreme heat (99th percentile of temperature) over
lags 0-21days were 3.75 (95% confidence interval [CI]: 1.63, 8.63) and 2.45
(95%CI: 1.15, 5.33), respectively, compared with the referent temperature (28
degrees C).This study suggested that both cold and hot temperatures could
significantly increase the risk of OHCA in Guangzhou, China. Our results might
have important public health implications for the prevention of OHCA.
PMID- 27497033
TI - Litter and nutrient flows in tropical upland forest flooded by a hydropower plant
in the Amazonian basin.
AB - Extensive areas in the Brazilian Amazon have been flooded for the construction of
hydroelectric dams. However, the water regime of these areas affects the dynamics
of igarapes (streams) in adjacent terra firme (upland forests). When the
reservoirs are filled, the water levels of streams rise above the normal levels
and upland bank forests are flooded. We investigated how this flooding affects
the litterfall and nutrient input in the upland forests upstream of a
hydroelectric dam reservoir in the Central Amazonia. When the reservoir was
filled, the forests were flooded and produced more than twice the litter
(8.80Mg.ha-1yr-1), with three times more leaves (6.36Mg.ha-1yr-1) than when they
were not flooded (4.20 and 1.92Mg.ha-1yr-1, respectively). During flooding, the
decomposition rate was four times lower in flooded forests (0.328g.g-1yr-1) than
in control forests (1.460g.g-1yr-1). Despite this, the flooding did not favor
litter or nutrient accumulation. Therefore, dam construction changes the organic
matter and nutrient cycling in upland Amazon rainforests. This may influence the
important role that they play in organic matter dynamics and could have
consequences for the regional carbon balance and, ultimately, global climate.
PMID- 27497034
TI - Sequestration and bioavailability of perfluoroalkyl acids (PFAAs) in soils:
Implications for their underestimated risk.
AB - Different from typical hydrophobic organic contaminants (HOCs), perfluoroalkyl
acids (PFAAs) are more soluble in water and less partitioned to soil than the
HOCs. It remains unclear whether and to what extent PFAAs could be sequestrated
in soil. In this study, sequential extraction of PFAAs in soil and
bioaccumulation of PFAAs in earthworm were carried out to understand the
sequestration and bioavailability of PFAAs in soils with different soil organic
matter (SOM) and aged for different time periods (7 and 47d). Sequestration
occurred in different degrees depending on the amount and compositions of SOM in
soil, structural properties of PFAAs and aging time. Surprisingly, in one peat
soil with high fraction of organic carbon (foc, 59%), the PFAAs were completely
sequestrated in the soil. Aging might lead to further sequestration of PFAAs in
soil with relatively lower foc. As a consequence of sequestration, the
bioavailability of PFAAs in peat soils was reduced 3-10 times compared to that in
the plain farmland soil. However, the sequestrated PFAAs were still
bioaccumulative in earthworms to some extent. The results indicated that the risk
of PFAAs in field soil with high content of SOM could be underestimated if only
free PFAAs using mild solvent extraction were monitored.
PMID- 27497035
TI - Determination of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in
Brazilian cow milk.
AB - The determination of polychlorinated dibenzo-p-dioxins (PCDDs) and
polychlorinated dibenzofurans (PCDFs) in raw cow milks have never been reported
in Brazil. Since the consumption of food of animal origin, including milk and
dairy products, is the major source of human exposure to these compounds, this
study aimed to establish the levels and profile of seven PCDDs and ten PCDFs in
raw cow milk samples collected in eight Brazilian states which among the major
milk producer states. Raw milk samples were collected in 34 different dairy
cattle farms during the summer of 2013. All PCDD/Fs congeners were found at least
in some of the 34 samples studied. The octa-chlorinated congeners (OCDD and OCDF)
were ubiquitous and also present in high concentrations. The mean values of WHO
TEQ1998;2005 were respectively 1.66 and 1.36pgTEQg-1 fat and samples taken in Sao
Paulo showed the highest WHO-TEQ values (2.46 TEQ1998g-1 fat and 2.10pgTEQ2005g-1
fat). Although all samples showed some contamination level, all values were below
the limit established by European Union for total PCDD/Fs in cow milk (3pgWHO
TEQ1998g-1 fat). Principal Component Analysis (PCA) showed that OCDD and OCDF
were responsible for 73% and 20% of the total data variance, respectively and
they presented an independent behavior, probably as a result of distinct origins.
The use of TEQ as weights in the PCA, revealed the importance of the penta-chloro
congeners and it was possible to identify sample distribution patterns probably
associated with the main PeCDD and PeCDF. The importance of local sources to
PCDD/Fs concentrations is still to be evaluated and determined.
PMID- 27497036
TI - The sooner the better: innate immunity as a path toward the HIV cure.
AB - To combat the diverse pathogens that infect humans, the immune system has evolved
complex and diverse transcriptional signatures, which drive differential cellular
and humoral responses. These signatures are induced by immune receptor sensing of
pathogens and by cytokines produced at the earliest onset of infection. The
specific nature of immune activation is as critical to pathogen clearance as the
induction of an adaptive immune response. This is particularly true for HIV,
which has developed numerous immune evasion mechanisms. In this review, we will
highlight recent findings that show the differential role for early innate immune
responses in promoting infection versus clearance and demonstrate the need for
continued research on these pathways for development of effective HIV treatments.
PMID- 27497038
TI - Small bowel obstruction secondary to paravesical hernia.
AB - BACKGROUND: Bowel obstruction in the setting of the unscarred abdomen can be due
to a wide variety of causes. Internal hernias are a rare cause of bowel
obstruction with paravesical hernia being exceedingly rare. Paravesical hernia
should form part of the differential diagnosis in the patient presenting with
bowel obstruction. Prompt management and reduction of the incarcerated bowel are
essential. This will prevent further complications especially related to bowel
ischemia. CASE SUMMARY: The patient presented with a classical history of small
bowel obstruction. Abdominal X-ray revealed distended loops of small bowel and
absence of air in the rectum. An exploratory laparotomy revealed a paravesical
internal hernia. A loop of terminal ileum had incarcerated and was the cause of
the bowel obstruction. The defect was repaired after reducing the bowel and the
patient made an uneventful recovery. CONCLUSION: Internal paravesical hernia
although extremely rare should form part of the differential diagnosis in the
patient presenting with small bowel obstruction especially in the previously
unscarred abdomen. If the obstruction is complete then prompt exploration via
laparotomy or laparoscopy is required. Delays in definitive management may result
in marginally viable bowel becoming ischemic and requiring bowel resection.
PMID- 27497037
TI - Detection of bowel inflammation with fused DWI/T2 images versus contrast-enhanced
images in pediatric MR enterography with histopathologic correlation.
AB - PURPOSE: To evaluate the fused, colorized diffusion weighted imaging (DWI) and
anatomic T2 images compared to routine contrast-enhanced T1 images at pediatric
magnetic resonance enterography (MRE). METHODS: Fused, colorized DWI/T2 images
were created from patients with magnetic resonance enterography (MRE) and
colonoscopy/biopsy. Radiologists noted inflammation in five bowel segments
(terminal ileum-rectosigmoid colon) on postcontrast images and DWI/T2 images.
Test characteristics and agreement were calculated. RESULTS: For 20 patients,
sensitivity/specificity/positive predictive value (PPV)/negative predictive value
(NPV) were 0.53/0.90/0.77/0.76 for DWI/T2 and 0.45/0.90/0.72/0.73 for
postcontrast images. Intraobserver agreement was ?=0.45-0.73. Interobserver
agreement was ?=0.53 for DWI/T2 and ?=0.63 for postcontrast images. CONCLUSION:
DWI/T2 images are similar in sensitivity/specificity to contrast-enhanced images
and with moderate intra/interobserver reliability.
PMID- 27497039
TI - Left subclavian-carotid bypass in a 38-year old female with brain ischemic
symptoms secondary to Takayasu's arteritis: A case report.
AB - INTRODUCTION: Takayasu's arteritis (TA) is a rare form of vasculitis that affects
the aorta, its branches and pulmonary arteries. TA is primarily treated by
pharmacologic therapy; however revascularization procedures may be required to
treat organ ischemia. Evidence-based consensus regarding the indications for
surgical or endovascular therapy for patients with supra-aortic vessels lesions
remains unclear. PRESENTATION OF CASE: We herein present a female patient with
known TA since 2000, who experienced progressive and frequent episodes of
amaurosis fugax in the left eye for 4 months. Computed tomography angiography
(CTA) revealed focal stenotic segments in the right common carotid artery (CCA)
and internal carotid artery (ICA) and near occlusion of the proximal left CCA. We
opted to treat the left side first with open revascularization, and a subclavian
carotid bypass was performed using a 6 millimeters (mm) externally supported
ePTFE graft. Patient recovered well from the surgery, her neurological exam was
normal and she was discharged home in stable condition in postoperative day
three. At three months she remains symptoms-free and her bypass is patent.
DISCUSSION/CONCLUSION: This case illustrates the clinical presentation of TA
affecting both carotid arteries; open revascularization via carotid subclavian
bypass grafting was successfully performed with minimal morbidity, complete
resolution of symptoms and improvement of the patient's quality of life.
Revascularization procedures when indicated should be performed while the disease
is inactive and close surveillance is mandatory.
PMID- 27497040
TI - Emergency total proctocolectomy in an uninsured patient with Familial Adenomatous
Polyposis Syndrome and acute lower gastrointestinal hemorrhage in a community
hospital: A case report.
AB - INTRODUCTION: Rectal bleeding is the most common symptom of Familial Adenomatous
Polyposis (FAP). This case investigates the efficacy of emergency surgery for FAP
with total proctocolectomy end ileostomy for recurrent lower gastrointestinal
(GI) hemorrhage in an uninsured patient in a 266-bed community hospital. The
optimal treatment for FAP with acute lower GI hemorrhage and hemodynamic
compromise unresponsive to conservative management is unclear. PRESENTATION OF
CASE: A 41-year-old uninsured African American man with no past medical or family
history presented to the emergency department with hematochezia lasting three
days. A clinical diagnosis of FAP made on colonoscopy with biopsies revealed
villous and tubulovillous adenomas without dysplasia. After blood products
resuscitation, an emergency total proctocolectomy with end ileostomy was
performed. A staged ileal J pouch to anal anastomosis and creation of protective
loop ileostomy was performed months later after securing state funding. A final
loop ileostomy reversal occurred six weeks later. His self reported quality of
life is improved. DISCUSSION: Lower GI hemorrhage from FAP unresponsive to blood
products may require emergency total proctocolectomy and end ileostomy with a
staged ileal J pouch to anal anastomosis, which can be done in a community acute
care hospital for an uninsured patient. CONCLUSION: A total proctocolectomy is
feasible in the emergency setting in an uninsured patient with lower GI bleeding
and FAP. A staged ileal J pouch-anal anastomosis is easier to justify to the
hospital compared to a staged completion colectomy with proctectomy. It is
essential to monitor the ileo-anal anastomosis with anoscopy.
PMID- 27497041
TI - Uncommon presentation of orbital schwanomma: A case report.
AB - INTRODUCTION: Schwannomas are well-differentiated solitary benign tumors that
originate from the schwann cells of the nerve sheath, constitute 1-8% of all head
and neck tumors and 1-4% of the orbital tumors. SUMMARY OF THE CLINICAL CASE: A
57-year-old female patient visited our department, because she has a blindness of
the right eye associated with an irreducible exophthalmia classified grade III, 4
years ago. Radiological exploration showed a mass in the orbital cone in relation
to a probable optic nerve schwannoma confirmed by biopsy. The affected eye was
exenterated because of delayed diagnosis. DISCUSSION AND CONCLUSION: In this
review we discuss the pertinent clinical findings of this rare lesion and review
the literature relative to optic nerve and solitary orbital schwannomas and
insist that aggressive surgery with total mass removal should be warned by early
diagnosis.
PMID- 27497042
TI - Intraoperative ICG fluorescence contrast imaging of the main artery watershed
area in colorectal cancer surgery: Report of a case.
AB - INTRODUCTION: Visualization of the main artery watershed area may be useful for
determining the area that should be resected in colorectal cancer surgery.
Resection of the main artery watershed area may result in complete resection of
lymph nodes along the main artery and area of potential ischemia. PRESENTATION OF
CASE: A man in his 60s with a chief complaint of hematochezia visited our
hospital, was diagnosed with colorectal cancer and underwent surgery. A case that
underwent colorectal resection with intraoperative indocyanine green (ICG)
fluorescence angiography from the resection-side of the superior rectal artery
(SRA) in order to confirm the watershed area is reported. Observation was
performed using a PINPOINT((r)) bright-field, color, near-infrared fluorescence
camera, and the watershed area of the SRA fluoresced 33s after the intra-arterial
injection of ICG. After observation resection and anastomosis was performed. The
patient's postoperative course was good. DISCUSSION: The method is simple and can
be performed within a short time, and it enables visual evaluation of the blood
flow in the intestinal tract before anastomosis. CONCLUSION: This method can be
expected to provide useful information for complete resection of lymph nodes
along the main artery and area of potential ischemia.
PMID- 27497043
TI - The use of endo-vascular balloon tamponade technique for the removal of a
misplaced nephrostomy tube in the inferior vena cava: A case report.
AB - INTRODUCTION: Inadvertent placement of a nephrostomy tube into the inferior vena
cava (IVC) is an extremely rare complication with few reported cases in the
literature. CASE PRESENTATION: We present a lady with obstructive uropathy in a
solitary kidney in whom an attempt by the community radiologist to place a
nephrostomy tube was complicated by wrong insertion into the IVC. This report
illustrates how a safe non- surgical removal of this tube using an intravenous
balloon tamponade technique was successfully applied. DISCUSSION: Intravenous
placement of nephrostomy catheters into the inferior vena cava is extremely rare
complication. A few case reports have been published in the literature. The
majority of these cases were removed in the operating room under general
anesthesia. Using Intravenous balloon tamponade technique for removal has not
been previously reported. CONCLUSION: Intravenous balloon tamponade technique is
effective and is a good minimally invasive alternative to surgical removal of
misplaced nephrostomy tube from IVC.
PMID- 27497045
TI - Postponed pregnancies and risks of very advanced maternal age.
AB - QUESTIONS UNDER STUDY: To evaluate pregnancy outcome in pregnant women aged >=45
years, termed very advanced maternal age (VAMA). METHODS: We retrospectively
compared the outcome of pregnancies in VAMA patients with controls aged 30 years
at time of delivery. Subgroups of singleton and multiple pregnancies were also
analysed. Incidences of maternal and fetal adverse outcomes were measured.
Statistical significance was set at p <0.05. Odds ratios (ORs) were adjusted
where necessary. RESULTS: One hundred and twenty-seven VAMA pregnancies and 2066
control pregnancies of women aged 30 years were analysed. VAMA pregnancies had a
higher rate of maternal complications such as gestational hypertension (3.9% vs
0.6%; OR 6.5), preeclampsia (14.2% vs 3.0%; OR 5.4, adjusted OR 4.4) and
gestational diabetes (12.6% vs 3.6%; OR 3.8). Likewise, increased need for blood
transfusion (3.2% vs 0.7%; OR 4.8, adjusted OR 4.4) and prolonged hospitalisation
>7 days (37.8% vs 15.1%; OR 3.42) was found. Infant complications such as
prematurity (44.9% vs 16.2%; OR 4.2) and low birthweight <5th percentile (11.0%
vs 5.6%; OR 2.1) were also increased. CONCLUSION: Pregnant women of very advanced
maternal age (>=45 years) have significantly increased maternal and fetal risks.
Women postponing pregnancy or planning a pregnancy in very advanced age should be
informed about these risks, in particular before artificial reproductive
technologies are applied or "social freezing".
PMID- 27497044
TI - Influence of sympathetic activity in the control of peripheral microvascular tone
in preterm infants.
AB - BACKGROUND: Microvascular dysregulation following preterm birth is associated
with increased illness severity and hypotension, particularly in males.
Sympathetic nervous vascular regulation is evident in females. We hypothesized
that sympathetic dysfunction in male preterm infants may contribute to a failure
of peripheral microvascular vasoconstriction. METHODS: Microvascular blood flow
of infants 24-43 wk gestational age was assessed at 6, 24, and 72 h of age by
laser Doppler. Blood flow Fourier transformed frequency distribution spectra (low
frequency/high frequency ratio) were used to assess the influence of sympathetic
tone on microvascular regulation. Total sympathetic output was assessed as
urinary normetanephrine. RESULTS: Microvascular sympathetic activity at 24 h
postnatal age decreased in early preterm males, but not females. Peripheral
sympathetic activity increased with advancing postnatal age in females, but
decreased in males. In early preterm infants, total normetanephrine outputs
increase significantly with postnatal age, in both sexes. CONCLUSION: Sympathetic
activation following preterm birth is sexually dimorphic, with preterm males
having reduced sympathetic tone and reduced upregulation of sympathetic tone
following birth. There is evidence of a disconnect between central sympathetic
activity and local peripheral microcirculatory sympathetic drive. This may relate
to autonomic nervous immaturity and highlights the need to understand how preterm
birth may affect autonomic function.
PMID- 27497046
TI - Effects of stocking density on antioxidant status, metabolism and immune response
in juvenile turbot (Scophthalmus maximus).
AB - This study was designed to evaluate the physiological and immune responses of
juvenile turbot to stocking density. Turbot (average weight 185.4g) were reared
for 120days in a land based recirculating aquaculture system (RAS) under three
stocking densities: low density (LD, ~9.3-26.1kg/m2, initial to final density),
medium density (MD, ~13.6-38.2kg/m2) and high density (HD, ~19.1-52.3kg/m2). Fish
were sampled at days 0, 40, 80 and 120 to obtain growth parameters and liver
tissues. No significant difference was detected in growth, biochemical parameters
and gene expression among the three densities until at the final sampling (day
120). At the end of this trial, fish reared in HD group showed lower specific
growth rate (SGR) and mean weight than those reared in LD and MD groups.
Similarly, oxidative stress and metabolism analyses represented that antioxidants
(superoxide dismutase (SOD), catalase (CAT), glutathione (GSH)) and metabolic
enzymes (glycerol-3-phosphate dehydrogenase (G3PDH) and glucose-6-phosphate
dehydrogenase (G6PDH)) clearly reduced in the liver of turbot reared in HD group.
The gene expression data showed that glutathione S-transferase (GST), cytochrome
P450 1A (CYP1A), heat shock protein 70 (HSP 70) and metallothionein (MT) mRNA
levels were significantly up-regulated, and lysozyme (LYS) and hepcidin (HAMP)
mRNA levels were significantly down-regulated in HD group on day 120. Overall,
our results indicate that overly high stocking density might block the activities
of metabolic and antioxidant enzymes, and cause physiological stress and
immunosuppression in turbot.
PMID- 27497047
TI - Aquaporins and plant transpiration.
AB - Although transpiration and aquaporins have long been identified as two key
components influencing plant water status, it is only recently that their
relations have been investigated in detail. The present review first examines the
various facets of aquaporin function in stomatal guard cells and shows that it
involves transport of water but also of other molecules such as carbon dioxide
and hydrogen peroxide. At the whole plant level, changes in tissue hydraulics
mediated by root and shoot aquaporins can indirectly impact plant transpiration.
Recent studies also point to a feedback effect of transpiration on aquaporin
function. These mechanisms may contribute to the difference between isohydric and
anisohydric stomatal regulation of leaf water status. The contribution of
aquaporins to transpiration control goes far beyond the issue of water transport
during stomatal movements and involves emerging cellular and long-distance
signalling mechanisms which ultimately act on plant growth.
PMID- 27497048
TI - Allosteric communication pipelines in G-protein-coupled receptors.
AB - The binding of ligands to G-protein-coupled receptors (GPCRs) in the
extracellular region transmits the signal to the intracellular region to initiate
coupling to effector proteins. The mechanism of this allosteric communication
remains largely unexplored. Knowledge of the residues involved in the pipeline of
the allosteric communication from the extracellular to the intracellular region
will provide means to (a) design ligands with bias in potency towards one
signaling pathway over others, and (b) design allosteric modulators that show
subtype selectivity in GPCRs. In this review we describe the current state of the
computational methods that provide insights into the allosteric communication in
GPCRs and elucidate how this information can be used to design allosteric
modulators.
PMID- 27497049
TI - Validation of the laryngopharyngeal reflux color and texture recognition compared
to pH-probe monitoring.
AB - OBJECTIVE/HYPOTHESIS: The objective of this study was to determine the validity
of our laryngopharyngeal reflux (LPR) diagnostic system from our previous study
(Witt et al.) against the results of a standard pH probe monitoring. We
hypothesized that subjects with abnormal pH probe results demonstrate color and
texture abnormalities that would be classified as LPR according to artificial
neural network (ANN) analysis. STUDY DESIGN: Retrospective analysis. METHODS:
Eighty-two subjects, including 18 pH-positive, 11 pH-negative, and 53 control
subjects were tested for LPR through multichannel intraluminal impedance 24-hour
pH (MII-24pH) monitoring. Laryngoscopic images of all subjects were obtained. The
hue and texture values of seven areas of interest, including true vocal folds,
false vocal folds, arytenoids, and interarytenoid, were quantified using a hue
calculation and two-dimensional Gabor filtering. These served as inputs for the
ANN. This was used to classify images through pattern recognition, and a receiver
operating characteristic (ROC) analysis was performed to determine the
effectiveness of the diagnosis. RESULTS: Classification accuracy for the combined
hue and texture was 87.40%, with an area under the ROC curve of 0.910.
CONCLUSION: Although a previous study conducted classification based on RFS, this
study suggests that color and texture analysis may be used to classify images
based on the results of pH probing, a more objective approach for diagnosis.
Additional studies should include more subjects to produce an even more accurate
reading, and will use the color/texture analysis tool to test and confirm this
application in a clinical setting. LEVEL OF EVIDENCE: 3B. Laryngoscope, 127:665
670, 2017.
PMID- 27497050
TI - Ocean acidification has little effect on developmental thermal windows of
echinoderms from Antarctica to the tropics.
AB - As the ocean warms, thermal tolerance of developmental stages may be a key driver
of changes in the geographical distributions and abundance of marine
invertebrates. Additional stressors such as ocean acidification may influence
developmental thermal windows and are therefore important considerations for
predicting distributions of species under climate change scenarios. The effects
of reduced seawater pH on the thermal windows of fertilization, embryology and
larval morphology were examined using five echinoderm species: two polar
(Sterechinus neumayeri and Odontaster validus), two temperate (Fellaster
zelandiae and Patiriella regularis) and one tropical (Arachnoides placenta).
Responses were examined across 12-13 temperatures ranging from -1.1 degrees C to
5.7 degrees C (S. neumayeri), -0.5 degrees C to 10.7 degrees C (O. validus),
5.8 degrees C to 27 degrees C (F. zelandiae), 6.0 degrees C to 27.1 degrees C
(P. regularis) and 13.9 degrees C to 34.8 degrees C (A. placenta) under present
day and near-future (2100+) ocean acidification conditions (-0.3 pH units) and
for three important early developmental stages 1) fertilization, 2) embryo
(prehatching) and 3) larval development. Thermal windows for fertilization were
broad and were not influenced by a pH decrease. Embryological development was
less thermotolerant. For O. validus, P. regularis and A. placenta, low pH reduced
normal development, albeit with no effect on thermal windows. Larval development
in all five species was affected by both temperature and pH; however, thermal
tolerance was not reduced by pH. Results of this study suggest that in terms of
fertilization and development, temperature will remain as the most important
factor influencing species' latitudinal distributions as the ocean continues to
warm and decrease in pH, and that there is little evidence of a synergistic
effect of temperature and ocean acidification on the thermal control of species
ranges.
PMID- 27497051
TI - Cell division of Streptococcus pneumoniae: think positive!
AB - Bacterial cell division is achieved by a dynamic protein complex called the
divisome. The accurate placement of the divisome, and more specifically that of
the tubulin-like protein FtsZ which forms the contractile Z-ring at mid-cell, is
finely regulated by different mechanisms tailored to each bacterial class. To
give rise to two viable daughter cells with the same genetic heritage and cell
shape, Streptococcus pneumoniae uses an original system that relies on the
membrane protein MapZ. This system is required for identifying the division site
as well as positioning the Z-ring at mid-cell. In addition, MapZ undergoes
phosphorylation by the serine/threonine kinase StkP and controls the constriction
of the Z-ring. Here, we discuss recent advances and concepts of the MapZ system.
PMID- 27497052
TI - The motility of Entamoeba histolytica: finding ways to understand intestinal
amoebiasis.
AB - The pathogenic amoeba Entamoeba histolytica is able to migrate within various
compartments of the human body. The present article reviews progress in
understanding the mechanisms of cell motility in E. histolytica during human
intestinal invasion and, in particular, how the three-dimensional characteristics
of the environment regulate the parasite's behaviour. The amoeboid mode of
migration that applies to E. histolytica's displacements on two-dimensional
surfaces is also expected to apply to the three-dimensional environment in the
human intestine although several unknown, distinct modalities may be involved.
Recent advances in the field of tissue engineering have provided clues on how the
construction of a human colon model could help us to understand the host's
intestinal physiology and its changes following amoebic infection.
PMID- 27497054
TI - Do German drivers use their smartphones safely?-Not really!
AB - Research in the laboratory as well as in naturalistic driving studies has shown
that texting while driving seems to be the most dangerous driver distraction.
However, there is still some discussion about the extent to which drivers adapt
their behavior to the traffic situation. Accordingly, they might use their phones
only in easy driving situations but refrain from doing so when driving becomes
more demanding. For Germany, no reliable data on these topics could be found
although overall smartphone use has also increased exponentially in this country.
As observational studies have proven to be an effective means to gather these
data, such a study was done observing 11,837 drivers in three big German cities
(Braunschweig, Hannover, Berlin) during daytime. An alarmingly high rate of
texting while driving was found (4.5%) as compared to other international
studies. This was even more frequent than the use of handheld (2.2%) and hands
free (1.7%) phones combined. Thus, there seems to be a special problem in Germany
with texting which should be further examined as this activity is highly
distracting. Finally, there was some indication that drivers adapt their
secondary task activities to the requirements of the driving task (e.g. somewhat
less texting when moving than when stationary at a red traffic light). However,
these adaptations were not very strong. Thus, drivers seem to underestimate the
dangers due to distraction. This could be a starting point for countermeasures
which increase this awareness of danger.
PMID- 27497053
TI - Biogenesis of the Gram-positive bacterial cell envelope.
AB - The Gram-positive cell envelope serves as a molecular platform for surface
display of capsular polysaccharides, wall teichoic acids (WTAs), lipoteichoic
acids (LTAs), lipoproteins, surface proteins and pili. WTAs, LTAs, and sortase
assembled pili are a few features that make the Gram-positive cell envelope
distinct from the Gram-negative counterpart. Interestingly, a set of LytR-CpsA
Psr family proteins, found in all Gram-positives but limited to a minority of
Gram-negative organisms, plays divergent functions, while decorating the cell
envelope with glycans. Furthermore, a phylum of Gram-positive bacteria, the
actinobacteria, appear to employ oxidative protein folding as the major folding
mechanism, typically occurring in an oxidizing environment of the Gram-negative
periplasm. These distinctive features will be highlighted, along with recent
findings in the cell envelope biogenesis.
PMID- 27497055
TI - Identifying cognitive distraction using steering wheel reversal rates.
AB - The influence of driver distraction on driving performance is not yet well
understood, but it can have detrimental effects on road safety. In this study, we
examined the effects of visual and non-visual distractions during driving, using
a high-fidelity driving simulator. The visual task was presented either at an
offset angle on an in-vehicle screen, or on the back of a moving lead vehicle.
Similar to results from previous studies in this area, non-visual (cognitive)
distraction resulted in improved lane keeping performance and increased gaze
concentration towards the centre of the road, compared to baseline driving, and
further examination of the steering control metrics indicated an increase in
steering wheel reversal rates, steering wheel acceleration, and steering entropy.
We show, for the first time, that when the visual task is presented centrally,
drivers' lane deviation reduces (similar to non-visual distraction), whilst
measures of steering control, overall, indicated more steering activity, compared
to baseline. When using a visual task that required the diversion of gaze to an
in-vehicle display, but without a manual element, lane keeping performance was
similar to baseline driving. Steering wheel reversal rates were found to
adequately tease apart the effects of non-visual distraction (increase of 0.5
degrees reversals) and visual distraction with offset gaze direction (increase
of 2.5 degrees reversals). These findings are discussed in terms of steering
control during different types of in-vehicle distraction, and the possible role
of manual interference by distracting secondary tasks.
PMID- 27497056
TI - In situ injection of phenylboronic acid based low molecular weight gels for
efficient chemotherapy.
AB - Injectable low molecular weight gels (LMWGs) based on the derivatives of
phenylboronic acid were prepared and used as substrates for efficient in situ
chemotherapy. The gelators as well as LMWGs were characterized by (1)H NMR, UV
vis, FTIR, MS and SEM. Anticancer drug doxorubicin hydrochloride (DOX) was
encapsulated in the gels. The rheological properties and rapid recovery
capability of both blank and drug-loaded gels were tested. The LMWGs were non
toxic to both 3T3 fibroblasts and 4T1 breast cancer cells. The gels were formed
rapidly after injected in vivo. The in vivo anticancer activities of DOX-loaded
LMWGs were investigated in breast cancer bearing mice. The intratumoral injection
of DOX loaded LMWGs with dose of 30 mg/kg revealed that the gels could coat
around the tumor tissues to release DOX sustainingly and maintain effective DOX
concentration for chemotherapy. The systemic toxicity of DOX was reduced
significantly with the in situ administration of LMWGs formulations. The
injectable LMWGs exhibited excellent therapeutic efficacy and low side effects in
local chemotherapy.
PMID- 27497057
TI - Nanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing
gastric cancer stem cell therapy.
AB - The cancer stem cell (CSC) hypothesis postulates that cancer cells overexpressing
CD44 are marked as CSCs that cause tumorigenesis and recurrence. This hypothesis
suggests that CD44 is a potential therapeutic target that can interfere with CSCs
qualities. MicroRNA-34a (miR-34a) is a promising candidate for CD44 repression
based cancer therapy as it has been reported to inhibit proliferation,
metastasis, and survival of CD44-positive CSCs. Here, we used nanovesicles
containing PLI/miR complexes (NVs/miR) to systemically deliver miR-34a and induce
miR-34a-triggered CD44 suppression in orthotopically and subcutaneously implanted
tumors in nude mice. Poly(l-lysine-graft-imidazole) (PLI) condenses miRs and is
functionally modified to deliver miRs to the site of action by buffering effect
of imidazole residues under endosomal pH. Indeed, NVs/miR consisting of PEGylated
lipids enveloping PLI/miR complexes greatly reduced inevitable toxicity of
polycations by compensating their surface charge and markedly improved their in
vivo stability and accumulation to tumor tissue compared to PLI/miR polyplexes.
Our NVs-mediated miR-34a delivery system specifically increased endogenous target
miR levels, thereby attenuating proliferation and migration of gastric cancer
cells by repressing the expression of CD44 with decreased levels of Bcl-2, Oct
3/4 and Nanog genes. Our strategy led to a greater therapeutic outcome than PLI
based delivery with highly selective tumor cell death and significantly delayed
tumor growth in CD44-positive tumor-bearing mouse models, thus providing a
fundamental therapeutic window for CSCs.
PMID- 27497058
TI - Valve interstitial cell tensional homeostasis directs calcification and
extracellular matrix remodeling processes via RhoA signaling.
AB - AIMS: Valve interstitial cells are active and aggressive players in aortic valve
calcification, but their dynamic mediation of mechanically-induced calcific
remodeling is not well understood. The goal of this study was to elucidate the
feedback loop between valve interstitial cell and calcification mechanics using a
novel three-dimensional culture system that allows investigation of the active
interplay between cells, disease, and the mechanical valve environment. METHODS &
RESULTS: We designed and characterized a novel bioreactor system for quantifying
aortic valve interstitial cell contractility in 3-D hydrogels in control and
osteogenic conditions over 14 days. Interstitial cells demonstrated a marked
ability to exert contractile force on their environment and to align collagen
fibers with the direction of tension. Osteogenic environment disrupted
interstitial cell contractility and led to disorganization of the collagen
matrix, concurrent with increased alphaSMA, TGF-beta, Runx2 and calcific nodule
formation. Interestingly, RhoA was also increased in osteogenic condition,
pointing to an aberrant hyperactivation of valve interstitial cells mechanical
activity in disease. This was confirmed by inhibition of RhoA experiments.
Inhibition of RhoA concurrent with osteogenic treatment reduced pro-osteogenic
signaling and calcific nodule formation. Time-course correlation analysis
indicated a significant correlation between interstitial cell remodeling of
collagen fibers and calcification events. CONCLUSIONS: Interstitial cell
contractility mediates internal stress state and organization of the aortic valve
extracellular matrix. Osteogenesis disrupts interstitial cell mechanical
phenotype and drives disorganization, nodule formation, and pro-calcific
signaling via a RhoA-dependent mechanism.
PMID- 27497059
TI - Miltefosine-loaded lipid nanoparticles: Improving miltefosine stability and
reducing its hemolytic potential toward erythtocytes and its cytotoxic effect on
macrophages.
AB - The toxic effects of miltefosine on the epithelial cells of the gastrointestinal
tract and its hemolytic action on erythrocytes have limited its use as an
antileishmanial agent. As part of our search for new strategies to overcome the
side effects of miltefosine during the treatment of leishmaniasis, we have
developed stable miltefosine-loaded lipid nanoparticles in an attempt to reduce
the toxic effects of the drug. We have evaluated lipid nanoparticles containing
varying amounts of miltefosine and cholesterol, prepared by sonication, in terms
of their physicochemical properties, preliminary stability, hemolytic potential
toward erythrocytes, and cytotoxicity to macrophages and to promastigote and
amastigote forms of Leishmania (L.) chagasi. Miltefosine loading into lipid
nanoparticles was 100% for low drug concentrations (7.0 to 20.0mg/mL). Particle
size decreased from 143nm (control) to between 43 and 69nm. From fluorescence
studies, it was observed that the presence of miltefosine and cholesterol (below
103MUM) promoted ordering effects in the phospholipid region of the
nanoparticles. The formulation containing 15mg/mL miltefosine was stable for at
least six months at 4 degrees C and in simulated gastrointestinal fluids, and did
not promote epithelial gastrointestinal irritability in Balb/C mice. When loaded
into lipid nanoparticles, the hemolytic potential of miltefosine and its
cytotoxicity to macrophages diminished, while its antiparasitic activity remained
unaltered. The results suggested that miltefosine-loaded lipid nanoparticles may
be promising for the treatment of leishmaniasis and might be suitable for oral
and parenteral use.
PMID- 27497060
TI - Macroscopic amyloid fiber formation by staphylococcal biofilm associated SuhB
protein.
AB - Staphylococcus aureus is a commensal and opportunistic pathogen that causes
lethal infections. Biofilm forming ability of S. aureus enhances its virulence
since biofilm provides the bacteria protective shield against antibiotics and
host immunity. Polysaccharide independent biofilm formation by several virulent
S. aureus strains have been identified recently, where protein components
substitute polysaccharide intercellular adhesin (PIA) involved in bacterial cell
attachment. The suhB gene has been reported to be essential in staphylococcal PIA
independent biofilm formation. Overexpression of staphylococcal SuhB (SasuhB) in
E. coli produces extracellular macroscopic fibers made of recombinant SaSuhB
protein. The amyloidic nature of the fiber is evaluated by high resolution
electron microscopy, X-ray fiber diffraction and amyloid specific dyes, such as
Congo red and thioflavin-T binding assay. The fibers appear to be sticky in
nature and bind a large number of bacterial cells. The results suggest the
possible role of SaSuhB-fibers as a structural component as well as an adhesin in
biofilm matrix.
PMID- 27497061
TI - Quantum dynamics of a hole migration through DNA: A single strand DNA model.
AB - A model predicting the behavior of a hole acting on the DNA strand was
investigated. The hole-DNA interaction on the basis of a quantum-classical, non
linear DNA single strand model was described. The fact that a DNA molecule is
formed by a furanose ring as its sugar, phosphate group and bases was taken into
consideration. Based on the model, results were obtained for the probability of a
hole location on the DNA base sequences, such as GTTGGG, GATGTGGG, GTTGTTGGG as
well as on the sugar-phosphate groups mated with them.
PMID- 27497062
TI - Habituation of self-reported anxiety and cortical hyper-vigilance during image
based exposure to spiders.
AB - BACKGROUND AND OBJECTIVES: The aim of the study was to examine habituation of
subjective anxiety and electrophysiological correlates of cortical hyper
vigilance during exposure to spider images among high (n = 12) and low (n = 11)
spider fear groups. METHODS: Participants viewed a six-stage hierarchy of spider
images. The images used at stage 1 and stage 6 were the same. Subjective anxiety
was rated at four intervals during each three-minute exposure stage (0, 60, 120,
and 180 s) and event-related potentials (ERPs) were averaged across these epochs
(0-60, 60-120, 120-180). RESULTS: High spider fearfuls demonstrated greater
habituation of self-reported anxiety within and between exposure stages compared
to low fearfuls. Consistent with attentional hyper-vigilance, the high-fear group
also demonstrated greater P1 amplitude in response to spider images. In both
groups, habituation of P1 amplitude was found at later relative to earlier
stages, but increased at stage six when the stage 1 image was re-presented,
despite low subjective anxiety. LIMITATIONS: While the passive viewing paradigm
mirrored image-based exposure, it was not possible to determine whether
participants engaged in avoidance strategies. In addition, further research is
needed to assess the relevance of habituation and reinstatement of P1 amplitude
to therapeutic outcome. CONCLUSIONS: Habituation of subjective anxiety during
image-based exposure is not necessarily accompanied by a reduction in measures of
cortical hyper-vigilance. The reinstatement of the P1 response may indicate
either re-activation of previous associations, less avoidance, or a more
generalised dishabituation mechanism.
PMID- 27497063
TI - Bone turnover markers and bone mineral density in healthy mother-daughter pairs
from South India.
AB - : Bone turnover markers (BTMs) provide important insights into the dynamics of
bone remodelling and are subjected to preanalytical and ethnic variations in
addition to influence of genetic and environmental factors. AIM/OBJECTIVES: To
derive ethnicity specific reference range for BTMs and to study their correlation
with Bone Mineral Density (BMD) in a cohort of healthy postmenopausal women and
their premenopausal daughters and to look at the impact of maternal bone mineral
status on daughters bone health. MATERIAL AND METHODS: This community based cross
sectional study included 300 subjects (150 mother-daughter pairs). Demographic
details were collected. Fasting blood and a second void morning urine samples
were obtained for measurement of BTMs (sCTX, sPTNP1, sOC and urine DPD
respectively) and bone mineral parameters. BMD was measured by DXA scan. RESULTS:
Osteoporosis was seen in 44.7% of the postmenopausal women. Ethnicity specific
reference ranges of BTMs were derived for the study population. Significant
inverse correlation was found between all BTMs (except urine DPD) and BMD(P <
0.05). Daughters of mothers with osteoporosis at spine and femoral neck had lower
BMD, compared to daughters of mothers without osteoporosis(P = 0.03 & 0.05).
CONCLUSION: Apart from deriving the ethnicity specific reference range for BTMs
and finding a significant inverse correlation between BTM and BMD, this study
found significantly lower BMD in daughters of mothers with osteoporosis at spine
and femoral neck implicating the probable interplay of genetic, epigenetic and
similar environmental factors.
PMID- 27497064
TI - A potential contribution of the less negatively charged cell wall to the high
aluminum tolerance of Rhodotorula taiwanensis RS1.
AB - Rhodotorula taiwanensis RS1 (Rt) is a high-aluminum (Al)-tolerant yeast that can
survive Al at concentrations up to 200 mM. In this study, we compared Rt with an
Al-sensitive congeneric strain, R. mucilaginosa AKU 4812 (Rm) and Al sensitive
mutant 1 (alsm1) of Rt, to explore the Al tolerance mechanisms of Rt. The growth
of Rm was completely inhibited by 1 mM Al, but that of Rt was not inhibited until
Al concentration was more than 70 mM. The growth of alsm1 was inhibited much more
by 70 mM and 100 mM Al than that of Rt. Compared with Rm cells, Rt cells
accumulated less Al in the cell wall and cytoplasm. A time-course analysis showed
that Al was absorbed by Rm cells much more rapidly than by Rt cells when exposed
to the same Al concentration. Meanwhile, the Al content of alsm1 was higher than
that of Rt. Although the cell wall of Rt was thicker than that of alsm1 and Rm
under control and 0.1 mM Al, that of Rt was thinner than that of alsm1 under 70
mM Al despite that their cell walls were thickened. The alcian blue adsorption
was lower and cell wall zeta-potential was higher in Rt and alsm1 than in Rm,
indicating a less negative charge of cell wall of Rt and alsm1 than that of Rm.
Taken together, the less negatively charged cell wall of Rt may restrict the
adsorption of cationic Al in cells, potentially contributing to its high Al
tolerance. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27497065
TI - Impaired cerebral blood flow networks in temporal lobe epilepsy with hippocampal
sclerosis: A graph theoretical approach.
AB - Graph theory is an emerging method to investigate brain networks. Altered
cerebral blood flow (CBF) has frequently been reported in temporal lobe epilepsy
(TLE), but graph theoretical findings of CBF are poorly understood. Here, we
explored graph theoretical networks of CBF in TLE using arterial spin labeling
imaging. We recruited patients with TLE and unilateral hippocampal sclerosis (HS)
(19 patients with left TLE, and 21 with right TLE) and 20 gender- and age-matched
healthy control subjects. We obtained all participants' CBF maps using pseudo
continuous arterial spin labeling and analyzed them using the Graph Analysis
Toolbox (GAT) software program. As a result, compared to the controls, the
patients with left TLE showed a significantly low clustering coefficient
(p=0.024), local efficiency (p=0.001), global efficiency (p=0.010), and high
transitivity (p=0.015), whereas the patients with right TLE showed significantly
high assortativity (p=0.046) and transitivity (p=0.011). The group with right TLE
also had high characteristic path length values (p=0.085), low global efficiency
(p=0.078), and low resilience to targeted attack (p=0.101) at a trend level.
Lower normalized clustering coefficient (p=0.081) in the left TLE and higher
normalized characteristic path length (p=0.089) in the right TLE were found also
at a trend level. Both the patients with left and right TLE showed significantly
decreased clustering in similar areas, i.e., the cingulate gyri, precuneus, and
occipital lobe. Our findings revealed differing left-right network metrics in
which an inefficient CBF network in left TLE and vulnerability to irritation in
right TLE are suggested. The left-right common finding of regional decreased
clustering might reflect impaired default-mode networks in TLE.
PMID- 27497066
TI - In vivo and in vitro disease modeling with CRISPR/Cas9.
AB - In the past few years, extensive progress has been made in the development of
genome-editing technology. Among several genome-editing tools, the clustered
regularly interspaced short palindrome repeat-associated Cas9 nuclease
(CRISPR/Cas9) system is particularly widely used owing to the ease of sequence
specific nuclease construction and the highly efficient introduction of
mutations. The CRISPR/Cas9 system was originally constructed to induce small
insertion and deletion mutations, but various methods have been developed to
introduce point mutations, deletions, insertions, chromosomal translocations and
so on. These methods should be useful for the reconstruction of disease-causing
mutations in cultured cell lines and living organisms to elucidate disease
pathogenesis and for disease prevention, treatment and drug discovery. This
review summarizes the current technical aspects of the CRISPR/Cas9 system for
disease modeling in cultured cells and living organisms, mainly mice.
PMID- 27497067
TI - Supervised learning events: direct observation of procedural skills pilot.
AB - BACKGROUND: Workplace-based assessment (WBA) is the assessment of specialist
competence based on what a trainee doctor actually does in the workplace. Between
January 2014 and January 2015, all UK occupational medicine (OM) trainees were
invited to test a suite of direct observation of procedural skills (DOPS) tools
designed in a supervised learning event (SLE) format. The Faculty of Occupational
Medicine (FOM) Workplace-Based Assessment Advisory Group (WBAAG) studied feedback
on the new format. AIMS: To assess the utility of the redesigned tools, including
their acceptability, feasibility, usability and key aspects of their reliability
and validity. METHODS: The face and content validity of the new forms were
assessed by a comprehension trial (CT), inter-rater reliability by a video
scoring exercise and usability and acceptability by an electronic survey of
trainees and trainers. RESULTS: The CT of trainees and trainers indicated that
the face and content validity of the revised tools were acceptable. Inter-rater
reliability video assessments indicated there was consistency of grading among
trainers. Sixty-eight per cent of trainees and 95% of trainers agreed that the
redesigned tools were an improvement on the current WBA DOPS tools and 83% of
trainees indicated the new tools encouraged them to reflect on their performance.
CONCLUSIONS: The results from this pilot study provided evidence to support a
request to the General Medical Council (GMC) for the new SLE-DOPS forms to be
used for WBA in OM. These changes were accepted by the GMC in January 2016 for
implementation in April 2016.
PMID- 27497068
TI - Effect of Clinical Pharmacist Intervention on Hemoglobin A1C Reduction in Veteran
Patients With Type 2 Diabetes in a Rural Setting.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM), if left uncontrolled, is associated
with significant morbidity and mortality. Patients in rural areas may not have
access to adequate resources to successfully treat diabetes. Clinical pharmacists
may be utilized to bridge this gap. OBJECTIVE: To evaluate the impact of a
clinical pharmacist on glycemic control in veterans with T2DM enrolled in a
rural, outpatient clinic. METHODS: Retrospective chart review was performed on
veterans with T2DM referred to the pharmacist-managed therapeutic monitoring
clinic at a community-based outpatient clinic located in rural Jackson, TN.
Patients served as their own controls. Patients with hemoglobin A1C (A1C) >=8%
were included. The primary outcome was A1C change from baseline in patients
managed by the clinical pharmacist. Secondary end points included blood pressure,
cholesterol, and weight. RESULTS: Of 111 veterans identified as having a A1C >=8%
in the pharmacist-managed clinic, 86 met inclusion criteria. At baseline, mean +/
SD A1C was 10.5% +/- 2.0% (range = 8.7%-16.2%). By the end of the intervention
period, mean A1C had decreased by 2.8 percentage points to 7.7% +/- 1.4% (P <
0.001). At the end of the intervention, 34% (n = 29) had a A1C of <7%, 40% (n =
34) between 7% and 7.9%, and only 6% (n = 5) >10% (P < 0.001). Improvements in
diastolic blood pressure (P = 0.001), total cholesterol (P = 0.001), and
triglyceride levels (P = 0.036) were also statistically significant when baseline
and intervention period values were compared. CONCLUSION: Pharmacist
interventions at a rural, outpatient clinic had a statistically significant
impact on A1C reduction in veterans with T2DM.
PMID- 27497069
TI - Ramsay Hunt syndrome.
PMID- 27497071
TI - Pediatric salivary gland carcinomas: Diagnostic and therapeutic management.
AB - OBJECTIVES/HYPOTHESIS: To analyze clinical presentations, treatment modalities,
and evolution of pediatric cases of salivary gland carcinomas to standardize care
for these rare diseases. STUDY DESIGN: Multicentric, retrospective study.
METHODS: We included in this retrospective study all children and adolescents
(aged <=18 years) treated from 1992 to 2012 in six pediatric centers in Paris,
France. Pathological tumor specimens of these cases were reviewed. RESULTS: Forty
three children were included (sex ratio male/female = 19/24, median age = 13
years). The parotid gland was the most common (37 cases) location for tumors.
Histological subtypes were mucoepidermoid carcinomas (n = 20), acinic cell
carcinomas (n = 14), and other (n = 9). Initial fine-needle aspiration was
performed in 15 cases (33%), and was concordant to final diagnosis in three cases
(20%). Primary surgery was performed in 42 patients, leading to a complete
microscopic resection in 80%. Associated lymph node dissection was performed in
28 patients (homolateral: 27, bilateral: 1) and showed lymph node metastases in
only two patients. One patient had distant metastases. Adjuvant irradiation was
delivered to 11 patients (median: 60 Gy; range: 50-65) and chemotherapy in five
cases. After a median follow-up of 5 years, six tumors relapsed, but no deaths
occurred. CONCLUSIONS: Childhood salivary gland carcinomas have a good prognosis
despite possible recurrences. Treatment is mainly based on surgery, with
simultaneous node dissection in cases of clinical or radiologic node enlargement.
Radiation therapy seems to be restricted to inoperable high-grade tumors or after
recurrence. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:140-147, 2017.
PMID- 27497072
TI - Large scale deep learning for computer aided detection of mammographic lesions.
AB - Recent advances in machine learning yielded new techniques to train deep neural
networks, which resulted in highly successful applications in many pattern
recognition tasks such as object detection and speech recognition. In this paper
we provide a head-to-head comparison between a state-of-the art in mammography
CAD system, relying on a manually designed feature set and a Convolutional Neural
Network (CNN), aiming for a system that can ultimately read mammograms
independently. Both systems are trained on a large data set of around 45,000
images and results show the CNN outperforms the traditional CAD system at low
sensitivity and performs comparable at high sensitivity. We subsequently
investigate to what extent features such as location and patient information and
commonly used manual features can still complement the network and see
improvements at high specificity over the CNN especially with location and
context features, which contain information not available to the CNN.
Additionally, a reader study was performed, where the network was compared to
certified screening radiologists on a patch level and we found no significant
difference between the network and the readers.
PMID- 27497070
TI - Association of genetic polymorphisms with survival of pancreatic ductal
adenocarcinoma patients.
AB - Germline genetic variability might contribute, at least partially, to the
survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently
performed genome-wide association studies (GWAS) on PDAC overall survival (OS)
suggested (P < 10(-5)) the association between 30 genomic regions and PDAC OS.
With the aim to highlight the true associations within these regions, we analyzed
44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722
PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We
observed statistically significant associations for five of the selected regions.
One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio
(HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes
for the minor allele] and one in the last intron of the RUNX2 gene on chromosome
6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are
of particular relevance. These loci do not coincide with those that showed the
strongest associations in the previous GWAS. In silico analysis strongly
suggested a possible mechanistic link between these two SNPs and pancreatic
cancer survival. Functional studies are warranted to confirm the link between
these genes (or other genes mapping in those regions) and PDAC prognosis in order
to understand whether these variants may have the potential to impact treatment
decisions and design of clinical trials.
PMID- 27497073
TI - RGD(Arg-Gly-Asp) internalized docetaxel-loaded pH sensitive liposomes:
Preparation, characterization and antitumor efficacy in vivo and in vitro.
AB - The goal of this research was to formulate dual-targeting liposomes (RGD/DTX-PSL)
that can selectively release loaded contents in a low pH level environment and to
actively target to the tumor using liposomes that had surface arginine-glycine
aspartic (RGD) tripeptides. We investigated whether RGD/DTX-PSL could serve as an
effective tumor-targeted nanoparticle that is capable of suppressing tumor
growth. The results suggest that DTX is released from liposomes faster at pH 5.0
than pH 7.4, demonstrating their pH sensitivity. RGD/DTX-PSL has a longer blood
circulation than Duopafei((r)) in rats. The RGD/DTX-PSL formulation displayed
stronger antiproliferative effects than DTX alone and the strongest inhibition of
tumor growth of the formulations tested, thus expanding therapeutic window of
DTX. In conclusion, we established a novel, promising and easy-to-handle liposome
formulation that has a considerable antitumor activity in vitro and in vivo. This
study provides important prerequisite for the clinical application of dual
targeting liposomes in delivering therapies.
PMID- 27497074
TI - Comparative analysis of new peptide conjugates of antitubercular drug candidates
Model membrane and in vitro studies.
AB - Novel peptide conjugates of two antitubercular drug candidates were synthesised
and characterised using new tuftsin peptide derivative (OT14) as carrier moiety.
As antitubercular drug candidates two pyridopyrimidine derivatives, TB803 (2
allylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) and TB820 (4-oxo-2
(pyrrolidin-1-yl)-pyrido[1,2-a]pyrimidin-3-carbaldehyde) inhibiting vital enzyme
of Mycobacterium tuberculosis were applied. Membrane affinity of the compounds
TB803 and TB820 and their peptide conjugates was evaluated using experimental
lipid mono- and bilayer models. Penetration ability was assessed tensiometrically
from Langmuir monolayer study and applying quartz crystal microbalance for the
supported lipid bilayer (SLB) system. Minimal inhibitory concentration (MIC)
values remained in a similar micromolar range for both of the conjugates while
their cellular uptake rate was improved significantly compared to the drug
candidates. A correlation was found between membrane affinity properties and
results of in vitro biological investigations. Analysis of physical/structural
properties of SLB in contact with bioactive components and visualization of the
structural change by atomic-force microscopy (AFM) provided information on the
type and route of molecular interaction of drug construction with lipid layers.
The possible role of electrostatic interactions between lipid layer and drug
candidates was tested in Langmuir-balance experiments using negatively charged
lipid mixture (DPPC+DPPG). Especially the peptide conjugates presented increased
membrane affinity due to cationic character of the peptide sequence selected for
the conjugate formation. That is supposed to be one reason for the enhanced
cellular uptake observed in vitro on MonoMac6 cell line. The conjugation of
antitubercular agents to a peptidic carrier is a promising approach to enhance
membrane affinity, cellular uptake rate and in vitro selectivity.
PMID- 27497075
TI - Tuning self-assembled morphology of the Abeta(16-22) peptide by substitution of
phenylalanine residues.
AB - The effects of the two phenylalanine (Phe) residues in the blocked Abeta(16-22)
peptide on its self-assembly have been investigated by replacing both of them
with two cyclohexylalanines (Chas) or two phenylglycines (Phgs). TEM and SANS
studies revealed that the flat and wide nanoribbons of Abeta(16-22) were
transformed into thin nanotubes when replaced with Chas, and thinner and twisted
nanofibrils when replaced with Phgs. The red-shifting degree of characteristic CD
peaks suggested an increased twisting in the self-assembly of the derivative
peptides, especially in the case of Ac-KLV(Phg)(Phg)AE-NH2. Furthermore,
molecular dynamics (MD) simulations also indicated the increasing trend in
twisting when Chas or Phgs were substituted for Phes. These results demonstrated
that the hydrophobic interactions and spatial conformation between Cha residues
were sufficient to cause lateral association of beta-sheets to twisted/helical
nanoribbons, which finally developed into nanotubes, while for Phg residue, the
loss of the rotational freedom of the aromatic ring induced much stronger steric
hindrance for the lateral stacking of Ac-KLV(Phg)(Phg)AE-NH2 beta-sheets,
eventually leading to the nanofibril formation. This study thus demonstrates that
both the aromatic structure and the steric conformation of Phe residues are
crucial in Abeta(16-22) self-assembly, especially in the significant lateral
association of beta-sheets.
PMID- 27497076
TI - RGD-TPGS decorated theranostic liposomes for brain targeted delivery.
AB - The aim of this work was to formulate RGD-TPGS decorated theranostic liposomes,
which contain both docetaxel (DTX) and quantum dots (QDs) for brain cancer
imaging and therapy. RGD conjugated TPGS (RGD-TPGS) was synthesized and
conjugation was confirmed by Fourier transform infrared (FTIR) spectroscopy and
electrospray ionisation (ESI) mass spectroscopy (ESI-MS). The theranostic
liposomes were prepared by the solvent injection method and characterized for
their particle size, polydispersity, zeta-potential, surface morphology, drug
encapsulation efficiency, and in-vitro release study. Biocompatibility and safety
of theranostic liposomes were studied by reactive oxygen species (ROS) generation
study and histopathology of brain. In-vivo study was performed for determination
of brain theranostic effects in comparison with marketed formulation (DocelTM)
and free QDs. The particle sizes of the non-targeted and targeted theranostic
liposomes were found in between 100 and 200nm. About 70% of drug encapsulation
efficiency was achieved with liposomes. The drug release from RGD-TPGS decorated
liposomes was sustained for more than 72h with 80% of drug release. The in-vivo
results demonstrated that RGD-TPGS decorated theranostic liposomes were 6.47- and
6.98-fold more effective than DocelTM after 2h and 4h treatments, respectively.
Further, RGD-TPGS decorated theranostic liposomes has reduced ROS generation
effectively, and did not show any signs of brain damage or edema in brain
histopathology. The results of this study have indicated that RGD-TPGS decorated
theranostic liposomes are promising carrier for brain theranostics.
PMID- 27497077
TI - A microwave resonator integrated on a polymer microfluidic chip.
AB - We describe a novel stacked split-ring type microwave (MW) resonator that is
integrated into a 10mm by 10mm sized microfluidic chip. A straightforward and
scalable batch fabrication process renders the chip suitable for single-use
applications. The resonator volume can be conveniently loaded with liquid sample
via microfluidic channels patterned into the mid layer of the chip. The proposed
MW resonator offers an alternative solution for compact in-field measurements,
such as low-field magnetic resonance (MR) experiments requiring convenient sample
exchange. A microstrip line was used to inductively couple MWs into the
resonator. We characterised the proposed resonator topology by electromagnetic
(EM) field simulations, a field perturbation method, as well as by return loss
measurements. Electron paramagnetic resonance (EPR) spectra at X-band frequencies
were recorded, revealing an electron-spin sensitivity of 3.7.10(11)spins.Hz(
1/2)G(-1) for a single EPR transition. Preliminary time-resolved EPR experiments
on light-induced triplet states in pentacene were performed to estimate the MW
conversion efficiency of the resonator.
PMID- 27497078
TI - Interactive effects of herbicide and enhanced UV-B on growth, oxidative damage
and the ascorbate-glutathione cycle in two Azolla species.
AB - A field experiment was conducted to investigate the impact of alone and combined
exposures of herbicide pretilachlor (5, 10 and 20MUgml(-1)) and enhanced UV-B
radiation (UV-B1; ambient +2.2kJm(-2) day(-1) and UV-B2; ambient +4.4kJm(-2) day(
1)) on growth, oxidative stress and the ascorbate-glutathione (AsA-GSH) cycle in
two agronomically important Azolla spp. viz., Azolla microphylla and Azolla
pinnata. Decreased relative growth rate (RGR) in both the species under tested
stress could be linked to enhanced oxidative stress, thus higher H2O2
accumulation was observed, that in turn might have caused severe damage to lipids
and proteins, thereby decreasing membrane stability. The effects were exacerbated
when spp. were exposed to combined treatments of enhanced UV-B and pretilachlor.
Detoxification of H2O2 is regulated by enzymes/metabolites of AsA-GSH cycle such
as ascorbate peroxidase (APX) and glutathione reductase (GR) activity that were
found to be stimulated. While, dehydroascorabte reductase (DHAR) activity, and
the amount of metabolites: ascorbate (AsA), glutathione (GSH) and ratios of
reduced/oxidized AsA (AsA/DHA) and GSH (GSH/GSSG), showed significant reduction
with increasing doses of both the stressors, either applied alone or in
combination. Glutathione-S-transferase (GST), an enzyme involved in scavenging of
xenobiotics, was found to be stimulated under the tested stress. This study
suggests that decline in DHAR activity and in AsA/DHA ratio might have led to
enhanced H2O2 accumulation, thus decreased RGR was noticed under tested stress in
both the species and the effect was more pronounced in A. pinnata. Owing to
better performance of AsA-GSH cycle in A. microphylla, this study substantiates
the view that A. microphylla is more tolerant than A. pinnata.
PMID- 27497079
TI - Selenate mitigates arsenite toxicity in rice (Oryza sativa L.) by reducing
arsenic uptake and ameliorates amino acid content and thiol metabolism.
AB - Arsenic (As) is a toxic element with the potential to cause health effects in
humans. Besides rice is a source of both amino acids (AAs) and mineral nutrients,
it is undesired source of As for billions of people consuming rice as the staple
food. Selenium (Se) is an essential metalloid, which can regulate As toxicity by
strengthening antioxidant potential. The present study was designed to
investigate As(III) stress mitigating effect of Se(VI) in rice. The level of As,
thiolic ligands and AAs was analyzed in rice seedlings after exposure to
As(III)/Se(VI) alone and As(III)+Se(VI) treatments. Selenate supplementation
(As(III) 25MUM+Se(VI) 25MUM) decreased total As accumulation in both root and
shoot (179 & 144%) as compared to As(III) alone treatment. The As(III)+Se(VI)
treatment also induced the levels of non-protein thiols (NPTs), glutathione (GSH)
and phytochelatins (PCs) as compared to As(III) alone treatment and also
modulated the activity of enzymes of thiol metabolism. The content of amino acids
(AAs) was significantly altered with Se(VI) supplementation. Importantly,
essential amino acids (EAAs) were enhanced in As(III)+Se(VI) treatment as
compared to As(III) alone treatment. In contrast, stress related non-essential
amino acids (NEAAs) like GABA, Glu, Gly, Pro and Cys showed enhanced levels in
As(III) alone treatment. In conclusion, rice supplemented with Se(VI) tolerated
As toxicity with reduced As accumulation and increased the nutrition quality by
increasing EAAs.
PMID- 27497080
TI - Transcriptional response of mysid crustacean, Americamysis bahia, is affected by
subchronic exposure to nonylphenol.
AB - Nonylphenol (NP) has been classified as an endocrine-disrupting chemical. In this
study, we conducted mysid DNA microarray analysis with which has 2240 oligo DNA
probes to observe differential gene expressions in mysid crustacean (Americamysis
bahia) exposed to 1, 3, 10 and 30 MUg/l of NP for 14 days. As a result, we found
31, 27, 39 and 68 genes were differentially expressed in the respective
concentrations. Among these genes, the expressions of five particular genes were
regulated in a similar manner at all concentrations of the NP exposure. So, we
focused on one gene encoding cuticle protein, and another encoding cuticular
protein analogous to peritrophins 1-H precursor. These genes were down-regulated
by NP exposure in a dose-dependent manner, and it suggested that they were
related in a reduction of the number of molting in mysids. Thus, they might
become useful molecular biomarker candidates to evaluate molting inhibition in
mysids.
PMID- 27497081
TI - Elimination of oral candidiasis may increase stimulated whole salivary flow rate.
AB - OBJECTIVES: Candida infections are frequently encountered fungal infections in
the oral mucosa. This study aimed to evaluate the effect of eliminating Candida
spp. on stimulated whole salivary flow rate (SWS) in patients with oral
candidiasis. SUBJECTS AND METHODS: This study involved 66 patients with oral
candidiasis. Fifty-two consecutive patients, successfully treated by antifungal
therapy, were available to examine the effect of elimination of oral Candida spp.
on SWS (success group); the 14 patients who tested positive for Candida after
therapy were retrospectively included (control group). SWS were used to measure
saliva production. Moreover, tongue pain and xerostomia were evaluated using
visual analog score (VAS). RESULTS: By eliminating oral Candida spp., SWS
significantly increased in the success group after antifungal therapy [SWS: mean
value 0.89+/-0.51ml/min (median 0.82ml/min: 0.15-2.14) to mean value 1.16+/
0.58ml/min (median 1.05ml/min: 0.2-2.93), P<0.001]. Furthermore, VAS scores for
subjective tongue pain and xerostomia were significantly decreased compared with
those before therapy in the success group [xerostomia: mean value 52.5+/-28.8
(median 53: 9-100) to 24.2+/-1.6 (median 17: 0-70), tongue pain: mean value
52.6+/-27.2 (median 56: 1-93) to 15.3+/-18.0 (median 9: 0-62). P<0.001]. There
was no significant difference in SWS, subjective tongue pain, or xerostomia in
the control group after antifungal therapy. [SWS: mean value 1.08+/-0.83ml/min
(median 0.69ml/min: 0.2-2.7) to 0.98+/-0.59ml/min (median 0.8ml/min: 0.45-2.5),
P=0.65], [xerostomia: mean value 62.8+/-5.3 (median 62: 28-70) to 64.0+/-8.8
(median 64: 56-73), P=0.58, tongue pain: mean value 64.3+/-18.6 (median 67: 31
87) to 58.4+/-20.0 (median 8: 20-78), respectively; P=0.24] CONCLUSION: Our study
demonstrated that SWS may increase by eliminating oral Candida spp. in patients
with oral candidiasis.
PMID- 27497083
TI - Mapping distance-decay of cardiorespiratory disease risk related to neighborhood
environments.
AB - Neighborhood characteristics affect an individual's quality of life. Although
several studies have examined the relationship between neighborhood environments
and human health, we are unaware of studies that have examined the distance-decay
of this effect and then presented the risk results spatially. Our study is unique
in that is explores the health effects in a less developed country compared to
most studies that have focused on developed countries. The objective of our study
is to quantify the distance-decay cardiorespiratory diseases risk related to 28
neighborhood aspects in the Federal District, Brazil and present this information
spatially through risk maps of the region. Toward this end, we used a quantile
regression model to estimate risk and GIS modeling techniques to create risk
maps. Our analysis produced the following findings: i) a 2500 m increase in
highway length was associated with a 46% increase in cardiorespiratory diseases;
ii) 46,000 light vehicles in circulation (considering a buffer of <=500 m from
residences) was associated with 6 hospital admissions (95% CI: 2.6, 14.6) per
cardiorespiratory diseases; iii) 74,000 m2 of commercial areas (buffer <=1700 m)
was associated with 12 hospital admissions (95% CI: 2.2, 20.8); iv) 1km2 increase
in green areas intra urban was associated with less two hospital admissions, and;
vi) those who live <=500 m from the nearest point of wildfire are more likely to
have cardiorespiratory diseases that those living >500 m. Our findings suggest
that the approach used in this study can be an option to improve the public
health policies.
PMID- 27497082
TI - Bisphenol A exposure and symptoms of anxiety and depression among inner city
children at 10-12 years of age.
AB - BACKGROUND: Experimental and epidemiological studies suggest that gestational
exposure to Bisphenol A (BPA), an ubiquitous endocrine disrupting chemical, may
lead to neurobehavioral problems in childhood; however, not all results have been
consistent. We previously reported a positive association between prenatal BPA
exposure and symptoms of anxiety/depression reported by the mother at child age 7
9 years in boys, but not girls. OBJECTIVES: Here, in the same birth cohort, we
investigated the association of prenatal BPA exposure with symptoms of depression
and anxiety self-reported by the 10-12 year olds, hypothesizing that we would
observe sex-specific differences in anxiety and depressive symptoms. METHODS:
African-American and Dominican women living in Northern Manhattan and their
children were followed from mother's pregnancy through children's age 10-12
years. BPA was quantified in maternal urine collected during the third trimester
of pregnancy and in child urine collected at ages 3 and 5 years. Children were
evaluated using the Revised Children's Manifest Anxiety Scale (RCMAS) and
Children's Depression Rating Scale (CDRS). We compared the children in the
highest tertile of BPA concentration to those in the lower two tertiles.
Associations between behavior and prenatal (maternal) BPA concentration or
postnatal (child) BPA concentration were assessed in regression models stratified
by sex. RESULTS: Significant positive associations between prenatal BPA and
symptoms of depression and anxiety were observed among boys. Postnatal BPA
exposure was not significantly associated with outcomes. There was substantial co
occurrence of anxiety and depressive symptoms in this sample. CONCLUSION: These
results provide evidence that prenatal BPA exposure is associated with more
symptoms of anxiety and depression in boys but not in girls at age 10-12 years.
PMID- 27497084
TI - Enhancing fatty acid production in Escherichia coli by Vitreoscilla hemoglobin
overexpression.
AB - Our recent 13 C-metabolic flux analysis (13 C-MFA) study indicates that energy
metabolism becomes a rate-limiting factor for fatty acid overproduction in E.
coli strains (after "Push-Pull-Block" based genetic modifications). To resolve
this bottleneck, Vitreoscilla hemoglobin (VHb, a membrane protein facilitating O2
transport) was introduced into a fatty-acid-producing strain to promote oxygen
supply and energy metabolism. The resulting strain, FAV50, achieved 70% percent
higher fatty acid titer than the parent strain in micro-aerobic shake tube
cultures. In high cell-density bioreactor fermentations, FAV50 achieved free
fatty acids at a titer of 7.02 g/L (51% of the theoretical yield). In addition to
"Push-Pull-Block-Power" strategies, our experiments and flux balance analysis
also revealed the fatty acid over-producing strain is sensitive to metabolic
burden and oxygen influx, and thus a careful evaluation of the cost-benefit
tradeoff with the guidance of fluxome analysis will be fundamental for the
rational design of synthetic biology strains. Biotechnol. Bioeng. 2017;114: 463
467. (c) 2016 Wiley Periodicals, Inc.
PMID- 27497085
TI - Distinct resting-state perfusion patterns underlie psychomotor retardation in
unipolar vs. bipolar depression.
AB - OBJECTIVE: Psychomotor abnormalities characterize both unipolar (UP) depression
and bipolar (BP) depression. We aimed to assess their neurobiological correlates
in terms of motor activity (AL) and resting-state cerebral blood flow (rCBF) and
investigate their association in BP, UP, and healthy controls (HC). METHOD: We
enrolled 42 depressed patients (22 BP, 20 UP) and 19 HC matched for age, gender,
education, income. AL and rCBF were objectively assessed with the use of wrist
actigraphy and arterial spin labeling. Group differences and the association of
AL and rCBF were computed. RESULTS: Activity level was significantly reduced in
patients, but no difference was found between BP and UP. Increased perfusion was
found in BP compared with UP and HC, in multiple brain areas. We found positive
correlations of rCBF and AL in BP and UP, in different parts of the insula and
frontal regions. Only BP showed a cluster in the left precentral gyrus. In HC,
only inverse correlations of AL and rCBF were found. CONCLUSION: The differences
in rCBF and in the localization of the clusters of positive AL/rCBF correlations
between BP and UP suggest that different neural impairments may underlie motor
symptoms in the two disorders, but finally converge in phenotypically similar
manifestations.
PMID- 27497086
TI - Improve biogas production from low-organic-content sludge through high-solids
anaerobic co-digestion with food waste.
AB - Anaerobic co-digestion of sewage sludge and food waste was tested at two
different total solid (TS) concentrations. In the low-solids group with TS 4.8%,
the biogas production increased linearly as the ratio of food waste in substrate
increased from 0 to 100%, but no synergetic effect was found between the two
substrates. Moreover, the additive food waste resulted in the accumulation of
volatile fatty acids and decelerated biogas production. Thus, the blend ratio of
food waste should be lower than 50%. While in the high-solids group with TS 14%,
the weak alkaline environment with pH 7.5-8.5 avoided excessive acidification but
high concentration of free ammonia was a potential risk. However, good synergetic
effect was found between the two substrates because the added food waste improved
mass transfer in sludge cake. Thus, 50% was recommended as the optimum ratio of
food waste in substrate because of the best synergetic effect.
PMID- 27497087
TI - Symbiotic hollow fiber membrane photobioreactor for microalgal growth and
bacterial wastewater treatment.
AB - A hollow fiber membrane photobioreactor (HFMP) for microalgal growth and
bacterial wastewater treatment was developed. C. vulgaris culture was circulated
through one side of the HFMP and P. putida culture was circulated through the
other. A symbiotic relationship was demonstrated as reflected by the photo
autotrophic growth of C. vulgaris using CO2 provided by P. putida and
biodegradation of 500mg/L glucose by P. putida utilizing photosynthetic O2
produced by C. vulgaris. Performance of the HFMP was significantly enhanced when
the microalgal culture was circulated through the lumen side of the HFMP: the
average percentage of glucose degraded per 8-h cycle was as high as 98% and
microalgal biomass productivity was increased by 69% compared to the reversed
orientation. Enhanced glucose biodegradation was achieved in an HFMP packed with
more fibers indicating the easy scalability of the HFMP for increased wastewater
treatment efficiency.
PMID- 27497088
TI - Role of biochar amendment in mitigation of nitrogen loss and greenhouse gas
emission during sewage sludge composting.
AB - The objective of the present study was to mitigate the greenhouse gas (GHG)
emissions during composting of dewatered fresh sewage sludge (DFSS) employing
biochar combined with zeolite (B+Z) and low dosage of lime (B+L). The 12% biochar
was mixed at a 10%, 15% and 30% of zeolite and 1% lime, while without any
additives was used as control. The results indicated that the combine use of B+Z
was significantly increased the enzymatic activities and reduced the ammonia loss
58.03-65.17% as compare to B+L amended treatment, while CH4 92.85-95.34% and N2O
95.14-97.28% decreased than control. The B+L1% amendment significantly increased
the organic matter degradation but the reduction was lower than B+Z and that
could reduce the CH4 and N2O emission by 55.17-63.08% and 62.24-65.53% as compare
to control, respectively. Overall our results demonstrated that 12%B+Z10%
addition into DFSS can be potentially used to improve the DFSS composting by
mitigation of GHG emission and nitrogen loss.
PMID- 27497089
TI - Hydro-liquefaction of microcrystalline cellulose, xylan and industrial lignin in
different supercritical solvents.
AB - The influences of solvent on hydro-liquefaction of cellulose, xylan, and lignin
were investigated using micro-autoclave. The maximum conversion and bio-oil yield
obtained from cellulose and xylan liquefaction were achieved in methanol, whereas
similar liquefaction characteristics of lignin were observed in methanol and
ethanol. The molecular simulation of interactions between solvents and
subcomponents indicated that methanol and ethanol were highly miscible with raw
materials. GC-MS and FT-ICR MS characterization revealed that the chemical
compositions of liquid products highly depended on the utilized feedstocks.
Esters, ketones, and aldehydes were mainly produced from cellulose and xylan
conversion, whereas aromatic compounds were primarily derived from lignin
conversion. EA results showed that methanol favored the hydrogenation and
deoxygenation, resulting in the heating value increased. It could be concluded
that the oil quality was highly improved in supercritical methanol.
PMID- 27497090
TI - A pivotal role of the jasmonic acid signal pathway in mediating radiation-induced
bystander effects in Arabidopsis thaliana.
AB - Although radiation-induced bystander effects (RIBE) in Arabidopsis thaliana have
been well demonstrated in vivo, little is known about their underlying
mechanisms, particularly with regard to the participating signaling molecules and
signaling pathways. In higher plants, jasmonic acid (JA) and its bioactive
derivatives are well accepted as systemic signal transducers that are produced in
response to various environmental stresses. It is therefore speculated that the
JA signal pathway might play a potential role in mediating radiation-induced
bystander signaling of root-to-shoot. In the present study, pretreatment of
seedlings with Salicylhydroxamic acid, an inhibitor of lipoxigenase (LOX) in JA
biosynthesis, significantly suppressed RIBE-mediated expression of the AtRAD54
gene. After root irradiation, the aerial parts of A. thaliana mutants deficient
in JA biosynthesis (aos) and signaling cascades (jar1-1) showed suppressed
induction of the AtRAD54 and AtRAD51 genes and TSI and 180-bp repeats, which have
been extensively used as endpoints of bystander genetic and epigenetic effects in
plants. These results suggest an involvement of the JA signal pathway in the RIBE
of plants. Using the root micro-grafting technique, the JA signal pathway was
shown to participate in both the generation of bystander signals in irradiated
root cells and radiation responses in the bystander aerial parts of plants. The
over-accumulation of endogenous JA in mutant fatty acid oxygenation up-regulated
2 (fou2), in which mutation of the Two Pore Channel 1 (TPC1) gene up-regulates
expression of the LOX and allene oxide synthase (AOS) genes, inhibited RIBE
mediated expression of the AtRAD54 gene, but up-regulated expression of the
AtKU70 and AtLIG4 genes in the non-homologous end joining (NHEJ) pathway.
Considering that NHEJ is employed by plants with increased DNA damage, the switch
from HR to NHEJ suggests that over-accumulation of endogenous JA might enhance
the radiosensitivity of plants in terms of RIBE.
PMID- 27497091
TI - Emerging roles of calcium-activated K channels and TRPV4 channels in lung oedema
and pulmonary circulatory collapse.
AB - It has been suggested that the transient receptor potential cation (TRP) channel
subfamily V (vanilloid) type 4 (TRPV4) and intermediate conductance calcium
activated potassium (KCa3.1) channels contribute to endothelium-dependent
vasodilation. Here, we summarize very recent evidence for a synergistic interplay
of TRPV4 and KCa3.1 channels in lung disease. Among the endothelial Ca2+
permeable TRPs, TRPV4 is best characterized and produces arterial dilation by
stimulating Ca2+ -dependent nitric oxide synthesis and endothelium-dependent
hyperpolarization. Besides these roles, some TRP channels control
endothelial/epithelial barrier functions and vascular integrity, while KCa3.1
channels provide the driving force required for Cl- and water transport in some
cells and most secretory epithelia. The three conditions, increased pulmonary
venous pressure caused by left heart disease, high inflation pressure and
chemically induced lung injury, may lead to activation of TRPV4 channels followed
by Ca2+ influx leading to activation of KCa3.1 channels in endothelial cells
ultimately leading to acute lung injury. We find that a deficiency in KCa3.1
channels protects against TRPV4-induced pulmonary arterial relaxation, fluid
extravasation, haemorrhage, pulmonary circulatory collapse and cardiac arrest in
vivo. These data identify KCa3.1 channels as crucial molecular components in
downstream TRPV4 signal transduction and as a potential target for the prevention
of undesired fluid extravasation, vasodilatation and pulmonary circulatory
collapse.
PMID- 27497092
TI - Effects of carvedilol on ventricular remodeling and the expression of beta3
adrenergic receptor in a diabetic rat model subjected myocardial infarction.
AB - BACKGROUND: This study was to assess effects of carvedilol on ventricular
remodeling and expression of beta3-adrenergic receptor (beta3-AR) and Gi protein
in a rat model of diabetes subjected to myocardial infarction (MI). METHODS: Rat
model of type II diabetes was established by injection of streptozotion. MI was
then induced by ligating the left anterior descending coronary artery. Rats were
then randomly divided into two groups treated with either placebo (PL) or
carvedilol (CA - 10mg.kg(-1).d(-)(1)). Additional controls consisted of sham
operated rats with diabetes (DS) and rats fed a normal diet subjected to
myocardial infarction (NM). Echocardiographic and hemodynamic studies were
performed to assess the structural and functional changes. beta3-AR and Gi mRNA
in the myocardium distal from the infarction region were measured, and beta3-AR
and Gi protein were measured with western blot. RESULTS: There were no
significant differences in MI size among the three MI groups. In the PL group,
LVEDd, LVWI, E/A and CVF were significantly increased, while LVEF and PW%
significantly decreased as compared with the DS and NM groups. Compared with the
DS group, the expression of beta3-AR and Gi mRNA and protein in the PL group was
significantly increased, however, in the CA group, beta3-AR and Gi mRNA and
protein were decreased. CONCLUSIONS: The expression of beta3-AR and Gi mRNA and
protein was increased in diabetic rats subjected to MI as compared with rats
subject to either condition alone. Carvedilol treatment prevented many of these
deleterious effects.
PMID- 27497093
TI - Prevalence of coronary macro- and micro-vascular dysfunctions after drug-eluting
stent implantation without in-stent restenosis.
AB - BACKGROUND: The aim was to examine the prevalence and characteristics of
epicardial vasomotor abnormality (EVA) and coronary microvascular dysfunction
(CMD) including endothelium-dependent (EDCMD) or -independent (EICMD) in patients
following a second-generation drug-eluting stent (second DES) implantation
without in-stent restenosis. METHODS AND RESULTS: In 105 patients who underwent
second DES implantation in the left anterior descending coronary artery (74 men;
mean age, 67.9+/-9.6years), and in 105 suspected angina patients without stenting
(65 men; mean age 66.4+/-9.1years), we evaluated EVA using the acetylcholine
provocation test, EDCMD and EICMD by measuring the coronary flow reserve and the
relationship between myocardial ischemia (intracoronary lactate production
between aorta and coronary sinus and ST-T changes) or recurrent angina and
vascular function. There was no difference in the incidence of EVA between DES
and control (49.5% versus 55.2%; P=0.41). Given that the prevalence of CMD was
higher in DES than in control (59.0% versus 29.5%; P<0.001), CMD may be
associated with stent placement. Of the CMD patients, EDCMD alone, EICMD alone,
and both CMDs were found in 40.3%, 22.6%, and 37.1%, respectively. Myocardial
ischemia was detected in 42.4% of patients, and recurrent angina was more common
in the presence of both EDCMD and EICMD in patients with EVA or CMD compared to
patients with normal vascular function (EVA, 42.9% versus 7.7%, P=0.015: CMD,
39.1% versus 7.7%, P=0.007). CONCLUSIONS: Myocardial ischemia and recurrent
angina may be caused by the presence of both EDCMD and EICMD after a second DES
implantation without ISR.
PMID- 27497094
TI - Serum sodium concentration, blood urea nitrogen, and outcomes in patients
hospitalized for acute decompensated heart failure.
AB - BACKGROUND: This study investigated the association of a low serum sodium and
elevated blood urea nitrogen (BUN) with outcomes in acute decompensated heart
failure (HF) patients. METHODS: Of the 4842 patients enrolled in the Acute
Decompensated Heart Failure Syndromes (ATTEND) registry, 4438 patients discharged
after hospitalization for acute decompensated HF were investigated to assess the
association of a low serum sodium and/or elevated BUN at discharge with all-cause
mortality. The patients were divided into four groups based on serum sodium (>136
or <=136mEq/l) and BUN (<25 or >=25mg/dl) at discharge. The median follow-up
period after discharge was 517 (381-776) days. RESULTS: According to multivariate
analysis, a low serum sodium (<=136mEq/l) or an elevated BUN (>=25mg/dl) was
significantly associated with a higher risk of all-cause death compared with
patients who had neither (hazard ratio [HR], 1.53; 95% confidence interval [CI],
1.22 to 1.94; P<0.001 and HR, 1.44; 95% CI, 1.19 to 1.73; P<0.001, respectively).
Patients with both low serum sodium and elevated BUN had a higher risk of all
cause death relative to patients with neither (HR, 2.64; 95% CI, 2.17 to 3.20;
P<0.001) and also relative to patients with either low serum sodium alone or
elevated BUN alone (HR, 1.72; 95% CI, 1.36 to 2.18; P<0.001 and HR, 1.84; 95% CI,
1.53 to 2.21; P<0.001, respectively). CONCLUSION: These findings demonstrated
that a low serum sodium and an elevated BUN may be additive risk factors for
postdischarge mortality in acute decompensated HF patients.
PMID- 27497095
TI - Impact of catheter tip-tissue contact on three-dimensional left atrial
geometries: Relationship between the external structures and anatomic distortion
of 3D fast anatomical mapping and high contact force guided images.
AB - BACKGROUND: A high catheter tip-tissue contact force (CF) with the myocardium may
cause 3-dimensional (3D) map distortion, however, the influence of external
structures surrounding the left atrium (LA) on that distortion remains unknown.
This study characterized the impact of high CF mapping on the local LA geometry
distortion. METHODS: Thirty AF patients underwent 3D-ultrasound merged with CT
images (3D-Merge-CT). The LA area in contact with external structures was
identified by enhanced CT. Fast-electroanatomical-mapping (FAM) geometries were
created by two methods, point-by-point mapping with high (>10g) CFs (high-CF
guided-FAM), followed by that with multielectrode-mapping catheters (conventional
FAM). The resulting geometries were compared with the 3D-Merge-CT images.
RESULTS: Three representative anatomical contact areas (ascending aorta-vs.
anterior wall, descending aorta-vs.-left pulmonary vein [PV], and vertebrae-vs.
posterior wall) were identified. The PV antrum distorted distance on the 3D-Merge
CT was significantly longer for high-CF guided-FAMs than conventional-FAMs (1.7[0
3.6] vs. 0[0-1.8]mm, P<0.0001). In high-CF maps, the distorted distance
significantly differed between regions with and without contact areas in both the
PV antrum (0[0-0.17] vs. 1.7[0-3.9]mm, P=0.0201) and LA body region (0[0-1.5] vs.
1.7[0.7-2.2]mm, P<0.005). The catheter tip-tissue CF did not correlate with the
distorted distance (r=0.08, P=0.46), and a multivariate analysis revealed that
the absence of anatomical contact areas was strongly associated with significant
local distortion, independent of the CF. CONCLUSIONS: High-CF guided mapping
yields greater 3D-image anatomical distortion than conventional-FAM methods. That
distortion was attenuated by regions with anatomical contact areas, suggesting
that regional anatomic distortion is involved in the existence of external
structures surrounding the LA.
PMID- 27497096
TI - Assessment of coronary flow reserve using a combination of planar first-pass
angiography and myocardial SPECT: Comparison with myocardial (15)O-water PET.
AB - Coronary flow reserve (CFR), defined as the ratio of maximum coronary flow
increase from baseline resting blood flow, is one of the most sensitive
parameters to detect early signs of coronary arteriosclerosis at the
microvascular level. Myocardial perfusion PET is a well-established technology
for CFR measurement, however, availability is still limited. The aim of this
study is to introduce and validate myocardial flow reserve measurement by
myocardial perfusion SPECT. METHODS: Myocardial perfusion SPECT at rest and ATP
stress (0.16mg/Kg/min) was performed in 10 patients with known coronary artery
disease. Immediately after the injection of Tc-99m sestamibi (MIBI), left
ventricular (LV) dynamic planar angiographic data were obtained for 90s. Coronary
flow reserve index as measured by MIBI SPECT (CFRMIBI) was calculated as follows:
CFRMIBI=CmsSbmb/CmbSbms, where subscripts b, s, Cm, and Sbm indicate baseline,
during stress, myocardial counts with MIBI SPECT, and integral of LV counts with
first pass angiography, respectively. Additionally, standard stress/rest (15)O
water PET to estimate CFR was performed in all patients as standard of reference.
RESULTS: CFRMIBI increased in conjunction with CFR, but underestimated blood flow
at high flow rates. The relationship between CFRMIBI (Y) and CFRPET (X) was well
fitted as follows: Y=1.40x(1-exp(1.79/x)) (r=0.84). CONCLUSIONS: The index of
CFRMIBI reflects the CFR by (15)O-water PET but underestimates flow at high
flows, maybe as a reflection of pharmacokinetic limitations of MIBI.
PMID- 27497097
TI - Exercise training bradycardia is largely explained by reduced intrinsic heart
rate.
AB - INTRODUCTION: Resting heart rate (RHR) declines with exercise training. Possible
mechanisms include: 1) increased parasympathetic tone, 2) decreased
responsiveness to beta-adrenergic stimulation, 3) decreased intrinsic heart rate
or 4) combination of these factors. OBJECTIVE: To determine whether an increase
in resting parasympathetic tone or decrease in response to beta-adrenergic
stimulation contributes to the decrease in RHR with training. METHODS: 51
screened healthy subjects aged 18-32 (n=20, mean age 26, 11 female) or 65-80
(n=31, mean age 69, 16 female) were tested before and after 6months of supervised
exercise training. Heart rate response to parasympathetic withdrawal was assessed
using atropine and beta-adrenergic responsiveness during parasympathetic
withdrawal using isoproterenol. RESULTS: Training increased VO2 max by 17%
(28.7+/-7.7 to 33.6+/-9.20ml/kg/min, P<0.001). RHR decreased from 62.8+/-6.6 to
57.6+/-7.2 beats per minute (P<0.0001). The increase in heart rate in response to
parasympathetic withdrawal was unchanged after training (+37.3+/-12.8 pre vs.
+36.4+/-12.2 beats per min post, P=0.41). There was no change in the heart rate
response to isoproterenol after parasympathetic blockade with training (+31.9+/
10.9 pre vs. +31.0+/-12.0 post beats per min, P=0.56). The findings were similar
in all four subgroups. CONCLUSIONS: We did not find evidence that an increase in
parasympathetic tone or a decrease in responsiveness to beta-adrenergic activity
accounts for the reduction in resting heart rate with exercise training. We
suggest that a decline in heart rate with training is most likely due to decrease
in the intrinsic heart rate.
PMID- 27497098
TI - Preclinical evaluation of a novel polyphosphazene surface modified stent.
AB - BACKGROUND: Treatment options for patients with coronary artery disease at high
risk for bleeding complications are limited. The aim of the current preclinical
study was to evaluate neointimal coverage, endothelial recovery, inflammation and
thrombogenicity in a novel thin-strut (71MUm thickness) Cobalt Chromium (CoCr)
stent modified with a nano-thin Polyzene(r)-F (PzF) surface coating. METHODS AND
RESULTS: Twenty-eight single PzF nano-coated stents and 20 bare metal control
stents (BMS) were implanted in the coronary arteries of 24 pigs, with scheduled 5
(n=5), 28- (n=13), and 90-day (n=6) follow-up in addition to overlapping
configuration (n=6 each), examined at 28-days. Histomorphometric analysis showed
significantly lower neointimal thickness in PzF nano-coated stents than BMS
controls at both 28- and 90-days (p=0.023 and 0.005) and reduced inflammation
(p=0.06 and 0.13). Endothelial coverage over luminal surfaces at all time points
was similar between nano-coated stents and BMS controls. We conducted
supplementary in-vitro experiments using human monocytes and an ex-vivo swine
carotid-jugular arterio-venous shunt model to better understand the healing
properties afforded by the PzF nano-coating. Overall, the PzF-nano-coating showed
reduced monocyte adhesion and thrombus formation compared to the un-coated
controls. CONCLUSIONS: Stents modified with a nano-thin PzF-coating implanted in
healthy swine indicate favorable vascular healing properties shown by reduced
neointimal hyperplasia and inflammation, along with resistance to thrombus
formation in an ex-vivo shunt model over unmodified stents.
PMID- 27497099
TI - Usefulness of the d-ROMs test for prediction of cardiovascular events.
AB - BACKGROUND: d-ROMs test developed to determine the degree of individual oxidative
stress may predict cardiovascular events. METHODS AND RESULTS: 265 patients (204
men, 61 women; age, 65+/-13years) who had been treated for cardiovascular disease
were divided evenly by quartile of baseline d-ROMs levels, and were followed up.
During the observation periods of 2.66+/-1.47years, there were 14 (5%) deaths, 8
(3%) cardiovascular deaths, 13 (5%) major adverse cardiovascular events (MACEs),
and 51 (19%) all cardiovascular events including heart failure, cardiovascular
surgery, and revascularization. Log-rank tests demonstrated that the patients in
the 4th quartile (d-ROMs?395.00U.CARR) had a higher incidence rate of
cardiovascular death than those in the 2nd quartile (d-ROMs 286.00-335.00,
p=0.022). In multivariate Cox regression analysis, even after adjustment for age,
sex, coronary risk factors, C-reactive protein, and renal function, high d-ROMs
was a risk factor for all-cause death [adjusted HR of 4th vs. 1st quartile,
10.791 (95% confidence interval 1.032-112.805), p=0.047], and all cardiovascular
events [HR of 4th vs. 1st quartile, 2.651 (95% confidence interval 1.138-6.177),
p=0.024]. CONCLUSIONS: Our results suggest that d-ROMs is a useful oxidative
stress marker to assess prognosis and risk of further cardiovascular events.
PMID- 27497100
TI - Increased risk of coronary artery calcification progression in subjects with high
baseline Lp(a) levels: The Kangbuk Samsung Health Study.
AB - BACKGROUND: Results from previous studies support the association of
lipoprotein(a) [Lp(a)] levels and coronary artery disease risk. In this study, we
analyzed the association between baseline Lp(a) levels and future progression of
coronary artery calcification (CAC) in apparently healthy Korean adults. METHODS:
A total of 2611 participants (mean age: 41years, 92% mend) who underwent a
routine health check-up in 2010 and 2014 were enrolled. Coronary artery calcium
score (CACS) were measured by multi-detector computed tomography. Baseline Lp(a)
was measured by high-sensitivity immunoturbidimetric assay. Progression of CAC
was defined as a change in CACS >0 over four years. RESULTS: Bivariate
correlation analyses with baseline Lp(a) and other metabolic parameters revealed
age, total cholesterol, HDL-C, LDL-C and CACS to have a significant positive
correlation, while body weight, fasting glucose level, blood pressure and
triglyceride level were negatively correlated with baseline Lp(a) level. After
four years of follow-up, 635 subjects (24.3%) had CAC progression. The
participants who had CAC progression were older, composed of more men, more
obese, and had higher fasting glucose levels and worse baseline lipid profiles
compared to those who did not have CAC progression. The mean serum Lp(a) level
was significantly higher in subjects who had CAC progression compared to those
who did not (32.5 vs. 28.9mg/dL, p<0.01). When the risk for CAC progression
according to baseline Lp(a) was calculated, those with Lp(a) level>=50mg/dL had
an odds ratio of 1.333 (95% CI 1.027-1.730) for CAC progression compared to those
with Lp(a)<50mg/dL after adjusting for confounding factors. CONCLUSIONS: In this
study, the subjects who had higher Lp(a) were at significantly higher risk for
CAC progression after four years of follow-up, suggesting the role of high Lp(a)
in CAC progression.
PMID- 27497101
TI - Pharmaceutical services as a tool to improve outcomes in patients with
cardiovascular diseases.
AB - Despite the presence of effective and safe pharmacotherapy, and availability of
multidimensional non-pharmacological treatment, the overall rate of major adverse
cardiovascular outcomes remains still unsatisfactory. The clinical pharmacy
activities and pharmaceutical care available in the community pharmacy settings
have a significant impact on outcomes in cardiovascular patients, e.g. adherence,
the level of blood pressure, total cholesterol or patients' health literacy.
Pharmaceutical care in patients diagnosed with cardiovascular diseases remains
beneficial both to the patients and the entire health care system. However, the
prediction of results of pharmacists' interventions is particularly difficult and
random. Many factors contribute to outcomes of community pharmacy services, e.g.
time spent with the patients or quality of communication between patients and
healthcare professionals. The most important issue in delivering effective
pharmaceutical care is to develop an evidence-based model. Globally, the
development of interprofessional collaboration between physicians and
pharmacists, and preparing more sophisticated pharmacoeconomics analyses in the
scope of pharmaceutical care are the next step in the improvement of advanced
pharmaceutical services. Further research, particularly based on real data on
this highly interesting topic is needed and recommended.
PMID- 27497102
TI - Age-dependent impact of new ESC-Guideline recommended door-to-balloon times on
mid-term survival in acute ST-elevation myocardial infarction patients undergoing
primary percutaneous coronary intervention.
AB - BACKGROUND: To investigate the age-dependent impact of the superfast door-to
balloon (D2B) times of <=60min as recommended by the new ESC Guideline for
patients with ST elevation myocardial infarction (STEMI) undergoing primary
percutaneous coronary intervention (PPCI) on mid-term survival rates based on a
single center registry dataset. PATIENTS AND METHODS: This study enrolled
consecutive STEMI patients who underwent PPCI from Jan 1, 2009 through Sep 30,
2013. We compared demographics, clinical characteristics and the D2B-survival
relationships between patients aged >=65 and <65. RESULTS: The younger group
comprised 242 patients (68%) aged <65 and the elder group consisted of 115
patients (32%) aged >=65. In patients aged <65, the mortality rate decreased
linearly with D2B time shortening (>90min vs. 61-90min vs. <=60min=14.9% vs.
13.3% vs. 1.2%, P=0.001). Contrarily, shortening of D2B time was not associated
with reduced mortality rate in patients aged >=65 (>90min vs. 61-90min vs.
<=60min=23.5% vs. 19% vs. 18.9%, P=0.99). In younger patients but not the
elderly, a D2B time of <60min has sufficient power to predict mortality with a
sensitivity of 0.83, specificity of 0.74, and Youden index of 0.57. CONCLUSIONS:
Our results show that the new ESC Guideline recommendation of D2B time <=60min is
associated with better survival rates in younger STEMI patients undergoing PPCI.
Our findings stress the importance of guideline adherence to minimize reperfusion
delay to improve survival in these patients.
PMID- 27497103
TI - Biventricular unloading in patients with refractory cardiogenic shock.
AB - BACKGROUND: Cardiogenic shock remains a clinical challenge with high mortality
rate. Mechanical circulatory support (MCS) devices have become an integral
component of the therapeutic armamentarium expanding the treatment options for
refractory cardiogenic shock (RCS). METHODS: We included all consecutive patients
with biventricular unloading with Impella-2.5 and VA-ECMO admitted for RCS
between October 2013 and March 2015. Outcome data included survival to discharge,
bridging to VAD and 28-day mortality. RESULTS: A total of 17 patients were
included. Mean age was 63.3+/-10.5 and 15 (88%) patients were male. RCS resulted
from acute myocardial infarction in 14 (82%), acute myocarditis in 1 (6%) dilated
cardiomyopathy in 2 (12%) patients. Mean SAPS II and SOFA score on admission was
74.7+/-16.86 and 11.16+/-1.79, respectively. Vasopressor doses and lactate levels
were significantly decreased within 72h on biventricular support (p=0.025 for
norepinephrine and p=0.005 for lactate). Nine (53%) patients died while on
support. Of the remaining 8 patients, 5 (29%) patients were weaned successfully
and discharged in cardiac rehabilitation and 3 (18%) patients were successfully
bridged to VAD. All 5 patients who were discharged to rehabilitation survived at
day 28 after discharge, while 1 of 3 VAD patients died after VAD implantation,
corresponding to an overall 28-day survival rate of 41%. CONCLUSIONS:
Biventricular support with Impella-2.5 and VA-ECMO in patients with RCS is
feasible and led to significant hemodynamic improvement and reduction of lactate
levels. Despite high severity scores, ICU- and 28-day mortality rates were better
than predicted.
PMID- 27497104
TI - What is/are the trigger(s) of takotsubo syndrome in cancer patients receiving
chemotherapy?
PMID- 27497105
TI - Successful treatment of 2 complex cases of international traveller's pulmonary
embolism using conventional therapy and novel oral anticoagulant.
PMID- 27497106
TI - Reversal of cardiac remodeling after treatment of IgG4 related cholangitis.
PMID- 27497107
TI - The prevention of statins against AKI and mortality following cardiac surgery: A
meta-analysis.
AB - OBJECTIVE: It is universally acknowledged that acute kidney injury (AKI) often
comes following cardiac surgery with severe morbidity and mortality. The impact
of statins on the incidence of AKI and mortality after cardiac surgery are
controversial, therefore, it is urgent to explore the source of heterogeneity via
the subgroup analysis. METHODS: We searched PubMed, ISI and Elsevier to May 31st
2016 for studies which investigated the effects of statins relevant to this
theme. Statistical analysis was using RevMan5.2 and Stata12.0. The outcomes were
the occurrence of AKI and the mortality after cardiac surgery. For the first
time, we discussed the source of heterogeneity on the basis of the characters of
patients in the following subgroup analysis. RESULTS: A total of 17 studies with
18,684 statins and 24,033 non-statin users were included. The meta-analysis
suggested that statins not only reduced the occurrence of AKI [Odds Ratio (OR)
0.72, 95% Confidence Interval (CI) 0.55-0.94)] in the subjects without high risk
factors, also decreased the mortality of the patients suffering AKI (OR 0.40, 95%
CI 0.22-0.72). CONCLUSION: Patients undergoing cardiac surgery might benefit from
statins by reducing the occurrence of AKI and the mortality of the patients
suffering AKI.
PMID- 27497108
TI - The time difference between clinical improvement and exercise tolerance increase
following pulmonary thromboendarterectomy.
PMID- 27497109
TI - Relation of body mass index (BMI) to the prevalence of hypertension in children:
A 3years' school-based prospective study in Suzhou, China.
AB - BACKGROUND: The prevalence of hypertension has been increasing in children and
adolescents in China, which is considered to be accompanied with the epidemic of
childhood overweight and obesity, but limited prospective studies have
investigated the effect of body mass index (BMI) change on blood pressure among
children, especially in China. METHODS: This school-based prospective study
compared the blood pressure and prevalence of hypertension in students with
different patterns of change in BMI between two periods (childhood and
adolescence). 5465 children were followed-up since 2011(childhood) in Suzhou,
China and had weight, height and blood pressure measured in 2011(childhood) and
2014(adolescence). RESULTS: Those who changed from being overweight in childhood
to having normal BMI in adolescence had similar mean blood pressures to those who
had a normal BMI at both two periods. In contrast, those who were overweight at
both two periods or who had a normal BMI in childhood and were overweight in
adolescence had higher blood pressure in adolescence than those who had a normal
BMI at both two periods. Compared with students who had a normal BMI at both
periods, those with combination of abnormal BMI in childhood and adolescence have
higher ORs of hypertension (4.83 in boys, 3.44 in girls and 3.73 in total).
CONCLUSION: These results suggest that obesity is a key determinant of blood
pressure during childhood, and weight reduction may have important beneficial
effects on blood pressure.
PMID- 27497111
TI - Association between mortality and incidence rates of coronary heart disease and
stroke: The Japan Public Health Center-based prospective (JPHC) study.
AB - BACKGROUND: It is essential to have information on incidence rates to estimate
the burden of cardiovascular diseases (CVD); however, it is not clear whether
mortality measurements are eligible for incidence estimations. METHODS: We
performed eight cohort studies from 1990 to 2010 in Japan, which consisted of
total 94,657 residents aged 40-59years who were followed-up for a median of
18.5years. Incidence and mortality rates for coronary heart disease (CHD) and
stroke events were ascertained. Sex-specified incidence rates were regressed to
the mortality rates, adjusting for differences in community and age group.
Further, incidence-to-mortality rate ratios were estimated using the Poisson
regression with random intercepts. RESULTS: CHD or stroke mortality rates were
highly associated with incidence rates in communities. Incidence-to-mortality
rate ratios were 2.06 (95% confidence interval, 1.56-2.73) in men and 1.41 (1.01
1.95) in women for CHD; and 3.99 (3.32-4.80) in men and 4.44 (3.73-5.29) in women
for stroke. There were no significant geographical variations in the ratio among
the 8 areas. CONCLUSIONS: We determined that it is possible to estimate CHD and
stroke occurrences in the population from their mortality rates reported in vital
statistics. Accordingly, we should pay attention to the communities in which
mortality rates due to CHD or stroke reported in vital statistics are higher, and
promote CVD prevention positively.
PMID- 27497110
TI - Long-term clinical outcome of titanium-nitride-oxide-coated stents versus
everolimus-eluting stents in acute coronary syndrome: Final report of the BASE
ACS trial.
AB - BACKGROUND: The BASE ACS randomized trial demonstrated non-inferiority of
titanium-nitride-oxide-coated bioactive stents (BAS), compared with everolimus
eluting stents (EES), for the primary endpoint of major adverse cardiac events
(MACE) in patients presenting with acute coronary syndrome (ACS) at 12-month
follow-up. We report the final long-term clinical outcome of the trial. METHODS:
We randomly assigned 827 patients with ACS to receive either BAS (417) or EES
(410). The primary endpoint was MACE: a composite of cardiac death, non-fatal
myocardial infarction (MI) or ischemia-driven target lesion revascularization
(TLR) at 12-month follow-up. Analysis was performed by intention to treat. Follow
up was planned at 12months, and yearly thereafter through 7years. RESULTS: Mean
follow-up duration was 4.2+/-1.9years (median 5.0years). At 5-year follow-up, BAS
was non-inferior to EES for the primary endpoint of MACE (14.4% versus 17.8%,
respectively; hazard ratio for BAS versus EES, 0.82; 95% confidence interval,
0.58-1.16; p=0.26 for superiority; p<0.001 for non-inferiority). The rate of non
fatal MI was lower in the BAS group (5.9% versus 9.7%, respectively, p=0.028).
The rates of cardiac death and ischemia-driven TLR were comparable (2.8% versus
3.8%, and 8.3% versus 9.9%; p=0.76 and p=0.58, respectively). CONCLUSIONS: In the
current final report of the randomized BASE ACS trial in patients with ACS, BAS
implantation was associated with a rate of cumulative MACE at long-term follow-up
that was statistically non-inferior to EES.
PMID- 27497112
TI - Usefulness of the catheter extension in combination with the fractional flow
reserve in coronary grafts.
PMID- 27497113
TI - Doping control container for urine stabilization: a pilot study.
AB - Urine collection containers used in the doping control collection procedure do
not provide a protective environment for urine, against degradation by
microorganisms and proteolytic enzymes. An in-house chemical stabilization
mixture was developed to tackle urine degradation problems encountered in human
sport samples, in cases of microbial contamination or proteolytic activity. The
mixture consists of antimicrobial substances and protease inhibitors for the
simultaneous inactivation of a wide range of proteolytic enzymes. It has already
been tested in lab-scale, as part of World Anti-Doping Agency's (WADA) funded
research project, in terms of efficiency against microbial and proteolytic
activity. The present work, funded also by WADA, is a follow-up study on the
improvement of chemical stabilization mixture composition, application mode and
limitation of interferences, using pilot urine collection containers, spray
coated in their internal surface with the chemical stabilization mixture. Urine
in plastic stabilized collection containers have been gone through various
incubation cycles to test for stabilization efficiency and analytical matrix
interferences by three WADA accredited Laboratories (Athens, Ghent, and Rome).
The spray-coated chemical stabilization mixture was tested against microorganism
elimination and steroid glucuronide degradation, as well as enzymatic breakdown
of proteins, such as intact hCG, recombinant erythropoietin and small peptides
(GHRPs, ipamorelin), induced by proteolytic enzymes. Potential analytical
interferences, observed in the presence of spray-coated chemical stabilization
mixture, were recorded using routine screening procedures. The results of the
current study support the application of the spray-coated plastic urine
container, in the doping control collection procedure. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27497114
TI - Investigating genomic and phenotypic parallelism between piscivorous and
planktivorous lake trout (Salvelinus namaycush) ecotypes by means of RADseq and
morphometrics analyses.
AB - Repeated adaptive ecological diversification has commonly been reported in fish
and has often been associated with trophic niche diversity. The main goal of this
study was to investigate the extent of parallelism in the genomic and phenotypic
divergence between piscivorous and planktivorous lake trout ecotypes from
Laurentian Shield lakes, Canada. This was achieved by documenting the extent of
morphological differentiation using geometric morphometrics and linear
measurements as well as the pattern of genomic divergence by means of RADseq
genotyping (3925 filtered SNPs) in 12 lakes. Our results indicate that the two
ecotypes evolved distinct body shape and several linear measurements in parallel.
Neutral genetic differentiation was pronounced between all isolated populations
(Mean FST = 0.433), indicating no or very limited migration and pronounced
genetic drift. Significant genetic differentiation also suggested partial
reproductive isolation between ecotypes in the two lakes where they are found in
sympatry. Combining different outlier detection methods, we identified 48 SNPs
putatively under divergent selection between ecotypes, among which 10 could be
annotated and related to functions such as developmental processes and ionic
regulation. Finally, our results indicate that parallel morphological divergence
is accompanied by both parallel and nonparallel genomic divergence, which is
associated with the use of different trophic niches between ecotypes. The results
are also discussed in the context of management and conservation of this highly
exploited species throughout northern North America.
PMID- 27497115
TI - Removal and Burial of Weed Seeds by Ants (Hymenoptera: Formicidae) From the Soil
Surface of a Cropped Area in Western Australia.
AB - Although granivorous ants are known to collect weed seeds from cropping areas in
Australia, the fate of these seeds has not been adequately investigated. Seeds of
annual ryegrass (Lolium rigidum Gaud.) and wild radish (Raphanus raphanistrum L.)
were placed around the nests of five native ant species (Iridomyrmex greensladei
Shattuck, Rhytidoponera metallica Smith, Melophorus turneri Forel, Monomorium
rothsteini Forel, and Pheidole hartmeyeri Forel) and tracked continuously over a
24-h period. Removal rates and seed preference of the ant species were evaluated.
Ant nests were then excavated to determine the placement of seeds that were taken
into each nest. Seed preference, seed removal efficiencies, activity, and seed
storage all varied between the ant species. Annual ryegrass seed was collected by
three species of ants and was removed from the soil surface more efficiently than
wild radish seed. Most ant species stored seed below ground at a depth that is
inhibitory to emergence, thereby potentially removing that portion of seed from
the seed bank, but some seed was placed at germinable depths. Pheidole hartmeyeri
was identified as a likely biological control agent for annual ryegrass seeds and
wild radish, while Me. turneri and Mo. rothsteini have potential as biocontrol
agents for annual ryegrass, but further research is needed.
PMID- 27497116
TI - Supercooling Points of Murgantia histrionica (Hemiptera: Pentatomidae) and Field
Mortality in the Mid-Atlantic United States Following Lethal Low Temperatures.
AB - The harlequin bug, Murgantia histrionica (Hahn), is a serious pest of
brassicaceous vegetables in southern North America. While this insect is limited
in its northern range of North America, presumably by severe cold winter
temperatures, specific information on its cold hardiness remains unknown. We
determined the supercooling points (SCPs) for Maryland and Virginia adult
populations and found no significant difference among these populations. SCPs
were similar for adults ([Formula: see text] = -10.35 degrees C; [Formula: see
text] 2.54) and early and late instar ([Formula: see text] = -11.00 degrees C;
[Formula: see text] 4.92) and between adult males and females. However, SCPs for
first instars ([Formula: see text] = -21.56 degrees C; [Formula: see text]1.47)
and eggs ([Formula: see text] = -23.24 degrees C; [Formula: see text]1.00) were
significantly lower. We also evaluated field survival of overwintering harlequin
bug adults during extreme cold episodes of January 2014 and January 2015, which
produced widespread air temperatures lower than -15 degrees C and subfreezing
soil temperatures in the Mid-Atlantic Region. After the 48-h episode in 2014, bug
mortality in exposed field sites averaged 88%, compared to <5% mortality of bugs
sheltered in an unheated greenhouse (recorded minimum temperature 4.4 degrees
C). After the 2015 episode, ~80% of adults that were established in the field the
previous November and then sheltered in an unheated garage during the episode,
died, in contrast to 96% mortality in exposed field sites. Our results provide
new information on M. histrionica overwintering biology, and thermal limitations
to its distribution, which leads to improved predictive capabilities to forecast
pest severity.
PMID- 27497117
TI - Prevalence and Amounts of Salmonella Found on Raw California Inshell Pistachios.
AB - After harvest, pistachios are hulled with mechanical abrasion and then separated
in a float tank containing water; the nuts that float (~15%; floaters) and those
that sink (~85%; sinkers) are dried and stored separately. To determine the
prevalence of Salmonella in pistachios, a total of 3,966 samples (1,032 floaters
and 2,934 sinkers) were collected within 4 months of the 2010, 2011, and 2012
harvests from storage silos (12 samples from each silo, in most cases) and were
stored at 4 degrees C; 100-g subsamples were enriched for the presence of
Salmonella. Twenty-one of the floater samples and 11 of the sinker samples were
positive for Salmonella: 2.0% prevalence (95% confidence interval [CI], 1.3 to
3.1%) and 0.37% prevalence (95% CI, 0.21 to 0.67%), respectively, for a weighted
average prevalence of 0.61%. Levels of Salmonella were determined for positive
samples using a most-probable-number (MPN) method with multiple 50-g, three 5.6
g, and three 0.56-g subsamples. Geometric mean levels of Salmonella in floaters
and sinkers were 0.66 MPN/100 g (0.14 to 5.3 MPN/100 g) and 0.18 MPN/100 g (0.10
to 0.62 MPN/100 g), respectively. Seven different serovars were identified among
the isolates, with nine pulsed-field gel electrophoresis fingerprints; as many as
four serovars were isolated from some samples. Salmonella serovars Montevideo
(44%), Enteritidis (19%), Senftenberg (16%), Worthington (12%), and Liverpool
(9.4%) were most commonly isolated from the initial 100-g samples. The prevalence
and levels of Salmonella in pistachios are within those observed for other tree
nuts, but the limited number of serovars isolated suggests a narrow and
persistent contamination source.
PMID- 27497118
TI - Effect of Hydrogen Peroxide in Combination with Minimal Thermal Treatment for
Reducing Bacterial Populations on Cantaloupe Rind Surfaces and Transfer to Fresh
Cut Pieces.
AB - Surface structure and biochemical characteristics of bacteria and produce play a
major role in how and where bacteria attach, complicating decontamination
treatments. Whole cantaloupe rind surfaces were inoculated with Salmonella,
Escherichia coli O157:H7, and Listeria monocytogenes at 10(7) CFU/ml. Average
population size of Salmonella, Escherichia coli O157:H7, and L. monocytogenes
recovered after surface inoculation was 4.8 +/- 0.12, 5.1 +/- 0.14, and 3.6 +/-
0.13 log CFU/cm(2), respectively. Inoculated melons were stored at 5 and 22
degrees C for 7 days before washing treatment interventions. Intervention
treatments used were (i) water (H2O) at 22 degrees C, (ii) H2O at 80 degrees C,
(iii) 3% hydrogen peroxide (H2O2) at 22 degrees C, and (iv) a combination of 3%
H2O2 and H2O at 80 degrees C for 300 s. The strength of pathogen attachment (SR
value) at days 0, 3, and 7 of storage was determined, and then the efficacy of
the intervention treatments to detach, kill, and reduce transfer of bacteria to
fresh-cut pieces during fresh-cut preparation was investigated. Populations of E.
coli O157:H7 attached to the rind surface at significantly higher levels (P <
0.05) than Salmonella and L. monocytogenes, but Salmonella exhibited the
strongest attachment (SR value) at all days tested. Washing with 3% H2O2 alone
led to significant reduction (P < 0.05) of bacteria and caused some changes in
bacterial cell morphology. A combination treatment with H2O and 3% H2O2 at 8
degrees C led to an average 4-log reduction of bacterial pathogens, and no
bacterial pathogens were detected in fresh-cut pieces prepared from this
combination treatment, including enriched fresh-cut samples. The results of this
study indicate that the microbial safety of fresh-cut pieces from treated
cantaloupes was improved at day 6 of storage at 5 degrees C and day 3 of storage
at 10 degrees C.
PMID- 27497119
TI - Spatial and Temporal Distribution of Escherichia coli on Beef Trimmings Obtained
from a Beef Packing Plant.
AB - The objective of this study was to determine the immediate source of Escherichia
coli on beef trimmings produced at a large packing plant by analyzing the E. coli
on trimmings at various locations of a combo bin filled on the same day and of
bins filled on different days. Ten 2,000-lb (907-kg) combo bins (B1 through B10)
of trimmings were obtained from a large plant on 6 days over a period of 5 weeks.
Thin slices of beef with a total area of approximately 100 cm(2) were excised
from five locations (four corners and the center) at each of four levels of the
bins: the top surface and 30, 60, and 90 cm below the top. The samples were
enriched for E. coli in modified tryptone soya broth supplemented with 20
mg/liter novobiocin. The positive enrichment cultures, as determined by PCR, were
plated on E. coli/coliform count plates for recovery of E. coli. Selected E. coli
isolates were genotyped using multiple-locus variable-number tandem repeat
analysis (MLVA). Of the 200 enrichment cultures, 43 were positive by PCR for E.
coli, and 32 of these cultures yielded E. coli isolates. Two bins did not yield
any positive enrichment cultures, and three PCR-positive bins did not yield any
E. coli isolates. MLVA of 165 E. coli isolates (30, 62, 56, 5, and 12 from B6
through B10, respectively) revealed nine distinct genotypes. MLVA types 263 and
89 were most prevalent overall and on individual days, accounting for 49.1 and
37.6% of the total isolates, respectively. These two genotypes were also found at
multiple locations within a bin. All nine genotypes belonged to the phylogenetic
group A0 of E. coli, suggesting an animal origin. The finding that the trimmings
carried very few E. coli indicates an overall effective control over
contamination of beef with E. coli at this processing plant. The lack of strain
diversity of the E. coli on trimmings suggests that most E. coli isolates may
have come from common sources, most likely equipment used in the fabrication
process.
PMID- 27497120
TI - Prevalence and Characterization of Salmonella enterica and Salmonella
Bacteriophages Recovered from Beef Cattle Feedlots in South Texas.
AB - Asymptomatic Salmonella carriage in beef cattle is a food safety concern, and the
beef feedlot environment may function as a reservoir of this pathogen. The goal
of this study was to identify and isolate Salmonella and Salmonella
bacteriophages from beef cattle feedlot environments in order to better
understand the microbial ecology of Salmonella and identify phages that might be
useful as anti-Salmonella beef safety interventions. Three feedlots in south
Texas were visited, and 27 distinct samples from each source were collected from
dropped feces, feed from feed bunks, drinking water from troughs, and soil in
cattle pens (n = 108 samples). Preenrichment, selective enrichment, and
selective/differential isolation of Salmonella were performed on each sample. A
representative subset of presumptive Salmonella isolates was prepared for
biochemical identification and serotyping. Samples were pooled by feedlot and
sample type to create 36 samples and enriched to recover phages. Recovered phages
were tested for host range against two panels of Salmonella hosts. Salmonella
bacteria were identified in 20 (18.5%) of 108 samples by biochemical and/or
serological testing. The serovars recovered included Salmonella enterica serovars
Anatum, Muenchen, Altona, Kralingen, Kentucky, and Montevideo; Salmonella Anatum
was the most frequently recovered serotype. Phage-positive samples were
distributed evenly over the three feedlots, suggesting that phage prevalence is
not strongly correlated with the presence of culturable Salmonella. Phages were
found more frequently in soil and feces than in feed and water samples. The
recovery of bacteriophages in the Salmonella-free feedlot suggests that phages
might play a role in suppressing the Salmonella population in a feedlot
environment.
PMID- 27497121
TI - Contamination Revealed by Indicator Microorganism Levels during Veal Processing.
AB - During site visits of veal processors, the U.S. Department of Agriculture, Food
Safety Inspection Service (FSIS) has reported processing deficiencies that likely
contribute to increased levels of veal contamination. Here, we report the results
of measuring aerobic plate count bacteria (APC), Enterobacteriaceae, coliforms
(CF), and Escherichia coli during eight sample collections at five veal
processors to assess contamination during the harvest of bob veal and formula-fed
veal before (n = 5 plants) and after (n = 3 plants) changes to interventions and
processing practices. Hides of veal calves at each plant had mean log CFU/100
cm(2) APC, Enterobacteriaceae, CF, and E. coli of 6.02 to 8.07, 2.95 to 5.24,
3.28 to 5.83, and 3.08 to 5.59, respectively. Preintervention carcasses had mean
log CFU/100 cm(2) APC, Enterobacteriaceae, CF, and E. coli of 3.08 to 5.22, 1.16
to 3.47, 0.21 to 3.06, and -0.07 to 3.10, respectively, before and 2.72 to 4.50,
0.99 to 2.76, 0.69 to 2.26, and 0.33 to 2.12, respectively, after changes were
made to improve sanitary dressing procedures. Final veal carcasses had mean log
CFU/100 cm(2) APC, Enterobacteriaceae, CF, and E. coli of 0.36 to 2.84, -0.21 to
1.59, -0.23 to 1.59, and -0.38 to 1.45 before and 0.44 to 2.64, -0.16 to 1.33,
0.42 to 1.20, and 0.48 to 1.09 after changes were made to improve carcass
directed interventions. Whereas the improved dressing procedures resulted in
improved carcass cleanliness, the changes to carcass-directed interventions were
less successful, and veal processors are urged to use techniques that ensure
uniform and consistent delivery of antimicrobials to carcasses. Analysis of
results comparing bob veal to formula-fed veal found bob veal hides,
preintervention carcasses, and final carcasses to have increased (P < 0.05) APC,
Enterobacteriaceae, CF, and E. coli (with the exception of hide
Enterobacteriaceae; P > 0.05) relative to formula fed veal. When both veal
categories were harvested at the same plant on the same day, similar results were
observed. Since identification by FSIS, the control of contamination during veal
processing has started to improve, but challenges still persist.
PMID- 27497122
TI - Isolation and Characterization of Antimicrobial-Resistant Nontyphoidal Salmonella
enterica Serovars from Imported Food Products.
AB - The objective of this study was to determine antimicrobial resistance and
elucidate the resistance mechanism in nontyphoidal Salmonella enterica serovars
isolated from food products imported into the United States from 2011 to 2013.
Food products contaminated with antimicrobial-resistant nontyphoidal S. enterica
were mainly imported from Taiwan, Indonesia, Vietnam, and China. PCR, DNA
sequencing, and plasmid analyses were used to characterize antimicrobial
resistance determinants. Twentythree of 110 S. enterica isolates were resistant
to various antimicrobial classes, including beta-lactam, aminoglycoside,
phenicol, glycopeptide, sulfonamide, trimethoprim, and/or fluoroquinolone
antimicrobial agents. Twelve of the isolates were multidrug resistant strains.
Antimicrobial resistance determinants blaTEM-1, blaCTX-M-9, blaOXA-1, tetA, tetB,
tetD, dfrA1, dfrV, dhfrI, dhfrXII, drf17, aadA1, aadA2, aadA5, orfC, qnrS, and
mutations of gyrA and parC were detected in one or more antimicrobial-resistant
nontyphoidal S. enterica strains. Plasmid profiles revealed that 12 of the 23
antimicrobial-resistant strains harbored plasmids with incompatibility groups
IncFIB, IncHI1, IncI1, IncN, IncW, and IncX. Epidemiologic and antimicrobial
resistance monitoring data combined with molecular characterization of
antimicrobial resistance determinants in Salmonella strains isolated from
imported food products may provide information that can be used to establish or
implement food safety programs to improve public health.
PMID- 27497123
TI - Disinfectant and Antimicrobial Susceptibility Profiles of the Big Six Non-O157
Shiga Toxin-Producing Escherichia coli Strains from Food Animals and Humans.
AB - The disinfectant and antimicrobial susceptibility profiles of 138 non-O157 Shiga
toxin-producing Escherichia coli strains (STECs) from food animals and humans
were determined. Antimicrobial resistance (AMR) was moderate (39.1% of strains)
in response to 15 antimicrobial agents. Animal strains had a lower AMR prevalence
(35.6%) than did human strains (43.9%) but a higher prevalence of the resistance
profile GEN-KAN-TET. A decreasing prevalence of AMR was found among animal
strains from serogroups O45 > O145 > O121 > O111 > O26 > O103 and among human
strains from serogroups O145 > O103 > O26 > O111 > O121 > O45. One animal strain
from serogroups O121 and O145 and one human strain from serogroup O26 had
extensive drug resistance. A high prevalence of AMR in animal O45 and O121
strains and no resistance or a low prevalence of resistance in human strains from
these serogroups suggests a source other than food animals for human exposure to
these strains. Among the 24 disinfectants evaluated, all strains were susceptible
to triclosan. Animal strains had a higher prevalence of resistance to
chlorhexidine than did human strains. Both animal and human strains had a similar
low prevalence of low-level benzalkonium chloride resistance, and animal and
human strains had similar susceptibility profiles for most other disinfectants.
Benzyldimethylammonium chlorides and C10AC were the primary active components in
disinfectants DC&R and P-128, respectively, against non-O157 STECs. A
disinfectant FS512 MIC >= 8 MUg/ml was more prevalent among animal O121 strains
(61.5%) than among human O121 strains (25%), which may also suggest a source of
human exposure to STEC O121 other than food animals. Bacterial inhibition was not
dependent solely on pH but was correlated with the presence of dissociated
organic acid species and some undissociated acids.
PMID- 27497124
TI - Virulence and Antibiotic and Heavy Metal Resistance of Vibrio parahaemolyticus
Isolated from Crustaceans and Shellfish in Shanghai, China.
AB - Vibrio parahaemolyticus can cause serious human seafoodborne gastroenteritis and
even death. In this study, we isolated and characterized 208 V. parahaemolyticus
strains from 10 species of commonly consumed crustaceans and shellfish available
in fish markets in Shanghai, People's Republic of China, in 2014. Most of these
aquatic species had not been detected previously. The results revealed an
extremely low occurrence of pathogenic V. parahaemolyticus carrying the toxin
gene trh (1.9%). However, a high level of resistance to the antibiotics
ampicillin (94.2%), rifampin (93.3%), and streptomycin (77.9%) was found.
Approximately 74.5% of the isolates had multidrug-resistant phenotypes. Tolerance
to the heavy metals Cu(2+), Pb(2+), and Cd(2+) was detected in the majority of
antibiotic resistant isolates. The resistance patterns differed depending on the
tested samples. The crustaceans Penaeus monodon and Marsupenaeus japonicus
harbored more antibiotic-resistant bacteria, whereas the isolates from the
crustacean Litopenaeus vannamei and the shellfish Busycon canaliculatus had high
tolerance to eight heavy metals tested. In contrast to the wide distribution of
multidrug resistance and tolerance to heavy metals, lower percentages of plasmid
DNA (22.6%) and SXT/R391-like integrative and conjugative elements (4.8%) were
detected in the isolates, suggesting that V. parahaemolyticus in these aquatic
species may have adopted some other molecular mechanisms that mediated the high
prevalence of resistance determinants. The results of this study support the need
for food safety risk assessment of aquatic products.
PMID- 27497125
TI - Enzymatic Digestion for Improved Bacteria Separation from Leafy Green Vegetables.
AB - An effective and rapid method for the separation of bacteria from food matrix
remains a bottleneck for rapid bacteria detection for food safety. Bacteria can
strongly attach to a food surface or internalize within the matrix, making their
isolation extremely difficult. Traditional methods of separating bacteria from
food routinely involve stomaching, blending, and shaking. However, these methods
may not be efficient at removing all the bacteria from complex matrices. Here, we
investigate the benefits of using enzyme digestion followed by immunomagnetic
separation to isolate Salmonella from spinach and lettuce. Enzymatic digestion
using pectinase and cellulase was able to break down the structure of the leafy
green vegetables, resulting in the detachment and release of Salmonella from the
leaves. Immunomagnetic separation of Salmonella from the liquefied sample allowed
an additional separation step to achieve a more pure sample without leaf debris
that may benefit additional downstream applications. We have investigated the
optimal combination of pectinase and cellulase for the digestion of spinach and
lettuce to improve sample detection yields. The concentrations of enzymes used to
digest the leaves were confirmed to have no significant effect on the viability
of the inoculated Salmonella. Results reported that the recovery of the
Salmonella from the produce after enzyme digestion of the leaves was
significantly higher (P < 0.05) than traditional sample preparation methods to
separate bacteria (stomaching and manually shaking). The results demonstrate the
potential for use of enzyme digestion prior to separation can improve the
efficiency of bacteria separation and increase the likelihood of detecting
pathogens in the final detection assay.
PMID- 27497126
TI - Enterotoxin Gene Profile and Molecular Characterization of Staphylococcus aureus
Isolates from Bovine Bulk Milk and Milk Products of Tigray Region, Northern
Ethiopia.
AB - Staphylococcal food poisoning (SFP) is an important foodborne disease worldwide,
and milk and milk products are commonly associated with SFP outbreaks. The
objectives of this study were to investigate the distribution of staphylococcal
enterotoxin (se) genes in Staphylococcus aureus from raw cow's milk and milk
products and to assess their genetic background with the spa typing method. Of
the 549 samples (297 bulk milk and 162 milk product samples) collected from
Tigray region, Northern Ethiopia, 160 (29.1%) were positive for S. aureus, of
which 82 (51%) were found to harbor se genes by a modified multiplex PCR. Nine se
genes were identified: sea (n = 12), seb (n = 3), sec (n = 3), sed(n = 4), seg (n
= 49), seh (n = 2), sei (n = 40), sej (n = 1), and tsst-1 (n = 24). The classical
type of genes accounted for 27%. Of the 82 enterotoxigenic isolates, 41.5 and
12.4% harbored two or more se genes, respectively. The highest gene association
was observed between sei and seg, whereas sea and seb were always found together
with the new types of se genes. Altogether, 18 genotypes of toxin genes were
identified, and 33% of the samples contained > 5 log CFU ml(-1) S. aureus. spa
typing identified 22 spa types and three novel spa sequences, which showed the
high genetic diversity of the isolates. No apparent relationship was observed
between spa type and se genes. Of the 25 spa types, 13 (52%) were from raw milk,
3 (12%) from milk products, and 9 (36%) from both types of sample. Types t314
(20.7%,n = 17), t458 (18.3%, n = 15), and t6218 (9.8%, n= 8) were the most common
spa types identified and were widely distributed in three of the eight studied
localities. This is the first study from the Tigray region to report the high
distribution of enterotoxigenic S. aureus with a diversified genetic background
from dairy food. The study may provide valuable data for microbial food safety
risk assessment, molecular epidemiology, and phylogenetic studies of S. aureus in
Ethiopia.
PMID- 27497127
TI - Inhibition of Listeria monocytogenes by Buffered Dry Vinegar in Reduced-Sodium
Ready-to-Eat Uncured Turkey Stored at 4 degrees C.
AB - A reduced-sodium ready-to-eat (RTE) uncured turkey was manufactured with buffered
dry vinegar treatments to validate the inhibition of Listeria monocytogenes and
spoilage microflora and to determine the effects on sensory and quality
attributes. Samples were stored at 4 degrees C for 12 weeks, and the study was
independently replicated three times. Two different five-strain inocula of L.
monocytogenes obtained from different sources were used for evaluating the
efficacy of the buffered dry vinegar treatments. The results showed that 0.6 and
0.8% buffered dry vinegar with a sodium base (BDV-SB) and buffered dry vinegar
with a potassium base (BDV-PB) at 0.7 and 0.9% controlled L. monocytogenes for 12
weeks. The untreated control product containing no buffered dry vinegar showed >1
log increase in L. monocytogenes populations counts at the end of 2 weeks.
Statistical analysis confirmed that the dry vinegar treatments inhibited (P >
0.05) the growth of L. monocytogenes compared with the untreated control. No
significant differences (P > 0.05) were seen in the inhibition of L.
monocytogenes between the two different five-strain inocula. Instrumental color
results showed no significant differences between the treatments. Purge loss
results showed no significant differences between the dry vinegar treatments, but
significant differences were seen between the untreated control and dry vinegar
treatments at a few testing intervals. The overall results indicated that the dry
vinegar ingredients (6.66 to 8.83 mM acetic acid in the finished product) were
effective in inhibiting L. monocytogenes obtained from multiple sources in
reduced-sodium RTE uncured turkey stored at 4 degrees C without adversely
impacting the quality attributes.
PMID- 27497128
TI - Antibacterial, Antibiofilm Effect of Burdock (Arctium lappa L.) Leaf Fraction and
Its Efficiency in Meat Preservation.
AB - First, the antibacterial, antibiofilm effect and chemical composition of burdock
(Arctium lappa L.) leaf fractions were studied. Then, the efficiency of burdock
leaf fractions in pork preservation was evaluated. The results showed that
burdock leaf fraction significantly inhibited the growth and biofilm development
of Escherichia coli and Salmonella Typhimurium. MICs of burdock leaf fractions on
E. coli and Salmonella Typhimurium were both 2 mg/ml. At a concentration of 2.0
mg/ml, the inhibition rates of the fraction on growth and development of E. coli
and Salmonella Typhimurium biofilms were 78.7 and 69.9%, respectively. During
storage, the log CFU per gram of meat samples treated with burdock leaf fractions
decreased 2.15, compared with the samples without treatment. The shelf life of
pork treated with burdock leaf fractions was extended 6 days compared with the
pork without treatment, and the sensory property was obviously improved. Compared
with the control group, burdock leaf fraction treatment significantly decreased
the total volatile basic nitrogen value and pH of the meat samples. Chemical
composition analysis showed that the burdock leaf fraction consisted of
chlorogenic acid, caffeic acid, p-coumaric acid, rutin, cynarin, crocin,
luteolin, arctiin, and quercetin. As a vegetable with an abundant source, burdock
leaf is safe, affordable, and efficient in meat preservation, indicating that
burdock leaf fraction is a promising natural preservative for pork.
PMID- 27497129
TI - Postharvest Control of Botrytis cinerea and Monilinia fructigena in Apples by
Gamma Irradiation Combined with Fumigation.
AB - To extend the shelf life of apples in South Korea, we evaluated the effect of
gamma irradiation alone or gamma irradiation combined with fumigation on the
control of postharvest decay caused by Botrytis cinerea and Monilinia fructigena.
An irradiation dose of 1.0 kGy caused the maximal inhibition of B. cinerea and M.
fructigena spore germination. The gamma irradiation dose required to reduce the
spore germination by 90% was 0.76 and 0.78 kGy for B. cinerea and M. fructigena,
respectively. Inhibition of conidial germination of both fungal pathogens
occurred at a greater level at the doses of 0.2 to 1.0 kGy compared with the
nontreated control; 0.2 kGy caused 90.5 and 73.9% inhibition of B. cinerea and M.
fructigena, respectively. Treatment in vitro with the ecofriendly fumigant
ethanedinitrile had a greater effect compared with the nontreated control. The in
vitro antifungal effects of the gamma irradiation and fumigation treatments
allowed us to further study the effects of the combined treatments.
Interestingly, when irradiation was combined with fumigation, the percentage of
disease inhibition increased more at lower (<0.4 kGy) than at higher doses of
irradiation, suggesting that the combined treatments reduced the necessary
irradiation dose in phytosanitary irradiation processing under storage
conditions.
PMID- 27497130
TI - Characterization of Shiga Toxin-Producing Escherichia coli O157 Isolates from
Bovine Carcasses.
AB - The main purpose of this study was to determine the prevalence of Escherichia
coli O157 on bovine carcasses before and after chilling at a large slaughterhouse
located in the city of Barcelona, Spain, to assess the effectiveness of dry
chilling on reducing E. coli O157 contamination of carcasses. In addition, the
study characterized the E. coli O157 strains isolated in terms of virulence
factors, antibiotic susceptibility, and their genetic diversity. Individual
bovine carcasses were sampled before (n = 300) and after (n = 300) chilling over
an 8-month period. Positive samples for E. coli O157 were subjected to virulence
screening by PCR (stx1, stx2, and eaeA genes and the fliCH7 gene), antimicrobial
susceptibility testing, and molecular typing by pulsed-field gel electrophoresis.
A total of 9.7% (29 of 300) of the nonrefrigerated carcasses examined and 2.3% (7
of 300) of the refrigerated carcasses were positive for E. coli O157. All the
isolates were serotype O157:H7, 92% (33 of 36) carried the stx1, stx2, and eaeA
genes, and 8% (3 of 36) carried the stx2 and eaeA genes. Antimicrobial
susceptibility testing showed a high degree of resistance: 29 strains (81%) were
resistant to at least 1 antimicrobial of the 12 antimicrobials tested; 69% (25 of
36) were resistant to 4 or more antimicrobials. Molecular typing by pulsed-field
gel electrophoresis found a high diversity of genetic types, implying little
cross-contamination in the slaughterhouse. This study confirms that E. coli
O157:H7 is present on the carcasses slaughtered in Spain, although its prevalence
is reduced by the dry chilling process used. The recovered isolates showed
potential pathogenesis and a high degree of multidrug resistance, confirming the
importance of bovine meat monitoring.
PMID- 27497131
TI - Prevalence of Antibiotic-Resistant Fecal Escherichia coli Isolates from Penned
Broiler and Scavenging Local Chickens in Arusha, Tanzania.
AB - We compared the prevalence of antibiotic-resistant Escherichia coli isolates from
household-level producers of broiler (commercial source breeds) and local
chickens in the Arusha District of Tanzania. Households were composed of a single
dwelling or residence with independent, penned broiler flocks. Free-range,
scavenging chickens were mixed breed and loosely associated with individual
households. A total of 1,800 E. coli isolates (1,200 from broiler and 600 from
scavenging local chickens) from 75 chickens were tested for their susceptibility
against 11 antibiotics by using breakpoint assays. Isolates from broiler chickens
harbored a higher prevalence of antibiotic-resistant E. coli relative to
scavenging local chickens, including sulfamethoxazole (80.3 versus 34%), followed
by trimethoprim (69.3 versus 27.7%), tetracycline (56.8 versus 20%), streptomycin
(52.7 versus 24.7%), amoxicillin (49.6 versus 17%), ampicillin (49.1 versus
16.8%), ciprofloxacin (21.9 versus 1.7%), and chloramphenicol (1.5 versus 1.2%).
Except for resistance to chloramphenicol, scavenging local chickens harbored
fewer resistant E. coli isolates (P < 0.05). Broiler chickens harbored more
isolates that were resistant to >=7 antibiotics (P < 0.05). The higher prevalence
of antibiotic-resistant E. coli from broiler chickens correlated with the
reported therapeutic and prophylactic use of antibiotics in this poultry
population. We suggest that improved biosecurity measures and increased
vaccination efforts would reduce reliance on antibiotics by these households.
PMID- 27497132
TI - Strain Diversity of Pseudomonas fluorescens Group with Potential Blue Pigment
Phenotype Isolated from Dairy Products.
AB - The blue discoloration in Mozzarella cheese comes from bacterial spoilage due to
contamination with Pseudomonas. Fourteen Pseudomonas fluorescens strains from
international collections and 55 new isolates of dominant bacterial populations
from spoiled fresh cheese samples were examined to assess genotypic and
phenotypic strain diversity. Isolates were identified by 16S rRNA gene sequencing
and tested for the production of the blue pigment at various temperatures on
Mascarpone agar and in Mozzarella preserving fluid (the salty water in which the
cheese is conserved, which becomes enriched by cheese minerals and peptides
during storage). Pulsed-field gel electrophoresis analysis after treatment with
the endonuclease SpeI separated the isolates into 42 genotypes at a similarity
level of 80%. Based on the pulsotype clustering, 12 representative strains
producing the blue discoloration were chosen for the multilocus sequence typing
targeting the gyrB, glnS, ileS, nuoD, recA, rpoB, and rpoD genes. Four new
sequence typing profiles were discovered, and the concatenated sequences of the
investigated loci grouped the tested strains into the so-called ''blue branch''
of the P. fluorescens phylogenetic tree, confirming the linkage between pigment
production and a specific genomic cluster. Growth temperature affected pigment
production; the blue discoloration appeared at 4 and 14 degrees C but not at 30
degrees C. Similarly, the carbon source influenced the phenomenon; the blue
phenotype was generated in the presence of glucose but not in the presence of
galactose, sodium succinate, sodium citrate, or sodium lactate.
PMID- 27497133
TI - Recipe Modification Improves Food Safety Practices during Cooking of Poultry.
AB - Many consumers do not practice proper food safety behaviors when preparing food
in the home. Several approaches have been taken to improve food safety behaviors
among consumers, but there still is a deficit in actual practice of these
behaviors. The objective of this study was to assess whether the introduction of
food safety instructions in recipes for chicken breasts and ground turkey patties
would improve consumers' food safety behaviors during preparation. In total, 155
consumers in two locations (Manhattan, KS, and Nashville, TN) were asked to
prepare a baked chicken breast and a ground turkey patty following recipes that
either did or did not contain food safety instructions. They were observed to
track hand washing and thermometer use. Participants who received recipes with
food safety instructions (n = 73) demonstrated significantly improved food safety
preparation behaviors compared with those who did not have food safety
instructions in the recipe (n = 82). In addition, the majority of consumers
stated that they thought the recipes with instructions were easy to use and that
they would be likely to use similar recipes at home. This study demonstrates that
recipes could be a good source of food safety information for consumers and that
they have the potential to improve behaviors to reduce foodborne illness.
PMID- 27497134
TI - Internalization of Listeria monocytogenes in Whole Avocado.
AB - In recent years, tree fruits have emerged as a new concern for Listeria
monocytogenes contamination. The objective of the current study was to evaluate
the potential internalization of L. monocytogenes from the surface of avocados
into the edible portions of the fruit during certain postharvest practices
simulated in a laboratory setting. One set of intact avocados was spot inoculated
with L. monocytogenes on the stem scar, and the second set was hydrocooled in
water contaminated with L. monocytogenes. Under these experimental conditions, L.
monocytogenes internalized into the avocado pulp through the stem or stem scar
after both spot inoculation and hydrocooling. In avocados spot inoculated with
50, 130, 500, and 1,300 CFU per fruit, bacteria were detected in the edible
portion adjacent to the stem scar within 15 days postinoculation during storage
at 4 degrees C. In avocados hydrocooled in water containing L. monocytogenes at
10(6) and 10(8) CFU/ml, bacteria reached the bottom end of the fruit, and the
populations in the edible portion adjacent to the stem scar reached up to 5.90 to
7.19 log CFU/g within 10 to 15 days during storage at 4 degrees C. Dye mixed with
inoculum was useful for guiding subsequent sampling, but dye penetration patterns
were not always consistent with bacterial penetration.
PMID- 27497135
TI - Prevalence of Multidrug-Resistant Bacteria on Fresh Vegetables Collected from
Farmers' Markets in Connecticut.
AB - This study determined the prevalence of multidrug-resistant (MDR) Acinetobacter
baumannii on fresh vegetables collected from farmers' markets in Connecticut. One
hundred samples each of fresh carrots, potatoes, and lettuce were sampled and
streaked on selective media, namely Leeds Acinetobacter and MDR Acinetobacter
agars. All morphologically different colonies from MDR Acinetobacter agar were
identified by using Gram staining, biochemical tests, and PCR. In addition,
susceptibility of the isolates to 10 antibiotics commonly used in humans, namely
imipenem, ceftriaxone, cefepime, minocycline, erythromycin, colistin-sulfate,
streptomycin, neomycin, doxycycline, and rifampin was determined by using an
antibiotic disk diffusion assay. The results revealed that only two samples of
potato and one sample of lettuce yielded A. baumannii. In addition, all carrot
samples were found to be negative for the organism. However, several other
opportunistic, MDR human pathogens, such as Burkholderia cepacia (1% potatoes, 5%
carrots, and none in lettuce), Stenotrophomonas maltophilia (6% potatoes, 2%
lettuce, and none in carrots), and Pseudomonas luteola (9% potatoes, 3% carrots,
and none in lettuce) were recovered from the vegetables. Antibiotic
susceptibility screening of the isolates revealed high resistance rates for the
following: ceftriaxone (6 of 6), colistin-sulfate (5 of 6), erythromycin (5 of
6), and streptomycin (4 of 6) in B. cepacia; colistin-sulfate (11 of 11) and
imipenem (10 of 11) in P. luteola; colistin-sulfate (8 of 8), ceftriaxone (8 of
8), cefepime (7 of 8), erythromycin (5 of 8), and imipenem (4 of 8) in S.
maltophilia; and imipenem (3 of 3), ceftriaxone (3 of 3), erythromycin (3 of 3),
and streptomycin (3 of 3) in A. baumannii. The results revealed the presence of
MDR bacteria, including human pathogens on fresh produce, thereby highlighting
the potential health risk in consumers, especially those with a compromised
immune system.
PMID- 27497136
TI - Nontuberculous Mycobacteria on Ready-to-Eat, Raw and Frozen Fruits and
Vegetables.
AB - The consumption of fruits and vegetables is increasing worldwide because of the
positive impact of these foods on human health. Ready-to-eat, raw whole, and
frozen fruits and vegetables were purchased from markets and examined for the
presence of nontuberculous mycobacteria (NTM) using culture, real-time PCR
(qPCR), and sequencing. Using qPCR, Mycobacterium sp. at 10(0) to 10(4) ge/g
(genome equivalents per gram) was found in almost all of the 178 samples; members
of the M. avium complex were found only sporadically. Culture and sequencing
revealed the presence of 22 viable NTM isolates in 17 samples. In addition to NTM
commonly found in the environment, several rarely described isolates of viable
NTM were recovered. The presence of Mycobacterium shigaense, which has been
previously isolated only from human patients, was found in lettuce, the first
time that this species has been found in an environmental sample. Mycobacterium
parmense, Mycobacterium palustre, and Mycobacterium llatzerense, which have been
previously isolated from human patients and occasionally from soil and water,
were recovered from leafy green vegetables. Strawberries and cut salad mixes
contained Mycobacterium algericum, Mycobacterium fallax, and Mycobacterium
minnesotense. NTM are primarily nonpathogenic. However, consumption of fruits or
vegetables contaminated with NTM could represent a health risk for
immunocompromised people, children, and the elderly.
PMID- 27497137
TI - Histology as a Valid Tool To Differentiate Fresh from Frozen-Thawed Marinated
Fish.
AB - European Commission Regulation (EU) 1276/2011 requires that fishery products
intended for raw consumption be frozen at -20 degrees C for not less than 24 h or
at -35 degrees C for at least 15 h in order to kill viable parasites other than
trematodes. But because marinating processes are not always effective in
destroying nematode larvae, raw marinated fish preparations should be frozen
before consumption. This study evaluated the performance of a standardized
histological method to distinguish between fresh and frozen-thawed raw marinated
fish. Sixty anchovy (Engraulis encrasicolus) fillets were sampled: 30 were
marinated at +4 degrees C for 24 h, and 30 were frozen at -20 degrees C for 24 h
before being marinated for 24 h. All 60 samples were fixed in formalin, processed
for paraffin embedding, cut, and stained with hematoxylin and eosin. The slide
preparations were examined microscopically by three independent histopathologists
and classified as frozen-thawed or negative according to standard operating
procedure criteria in use at our laboratory. Performance evaluation of the method
showed 100% sensitivity (95% confidence interval [CI], 88.4 to 100%) and 100%
specificity (95% CI, 88.4 to 100%), and the interrater agreement (Cohen's kappa)
was 1 (95% CI, 0.85 to 1). Histology proved a valid and reliable tool to
distinguish fresh from frozen-thawed marinated fish. It can be applied to deliver
safe raw fishery products to consumers in order to minimize the risk of
anisakidosis.
PMID- 27497138
TI - A composite indicator to measure universal health care coverage in India: way
forward for post-2015 health system performance monitoring framework.
AB - BACKGROUND: There is limited work done on developing methods for measurement of
universal health coverage. We undertook a study to develop a methodology and
demonstrate the practical application of empirically measuring the extent of
universal health coverage at district level. Additionally, we also develop a
composite indicator to measure UHC. METHODS: A cross-sectional survey was
undertaken among 51 656 households across 21 districts of Haryana state in India.
Using the WHO framework for UHC, we identified indicators of service coverage,
financial risk protection, equity and quality based on the Government of India
and the Haryana Government's proposed UHC benefit package. Geometric mean
approach was used to compute a composite UHC index (CUHCI). Various statistical
approaches to aggregate input indicators with or without weighting, along with
various incremental combinations of input indicators were tested in a
comprehensive sensitivity analysis. FINDINGS: The population coverage for
preventive and curative services is presented. Adjusting for inequality, the
coverage for all the indicators were less than the unadjusted coverage by 0.1
6.7% in absolute term and 0.1-27% in relative term. There was low unmet need for
curative care. However, about 11% outpatient consultations were from unqualified
providers. About 30% households incurred catastrophic health expenditures, which
rose to 38% among the poorest 20% population. Summary index (CUHCI) for UHC
varied from 12% in Mewat district to 71% in Kurukshetra district. The inequality
unadjusted coverage for UHC correlates highly with adjusted coverage. CONCLUSION:
Our paper is an attempt to develop a methodology to measure UHC. However, careful
inclusion of others indicators of service coverage is recommended for a
comprehensive measurement which captures the spirit of universality. Further,
more work needs to be done to incorporate quality in the measurement framework.
PMID- 27497139
TI - Incidence and determinants of hysterectomy in a low-income setting in Gujarat,
India.
AB - Hysterectomy is a leading reason for use of health insurance amongst low-income
women in India, but there are limited population-level data available to inform
policy. This paper reports on the findings of a mixed-methods study to estimate
incidence and identify predictors of hysterectomy in a low-income setting in
Gujarat, India. The estimated incidence of hysterectomy, 20.7/1000 woman- years
(95% CI: 14.0, 30.8), was considerably higher than reported from other countries,
at a relatively low mean age of 36 years. There was strong evidence that among
women of reproductive age, those with lower income and at least two children
underwent hysterectomy at higher rates. Nearly two-thirds of women undergoing
hysterectomy utilized private hospitals, while the remainder used government or
other non-profit facilities. Qualitative research suggested that weak sexual and
reproductive health services, a widespread perception that the post-reproductive
uterus is dispensable and lack of knowledge of side effects have resulted in the
normalization of hysterectomy. Hysterectomy appears to be promoted as a first or
second-line treatment for menstrual and gynaecological disorders that are
actually amenable to less invasive procedures. Most women sought at least two
medical opinions prior to hysterectomy, but both public and private providers
lacked equipment, skills and motivation to offer alternatives. Profit and
training benefits also appeared to play a role in some providers' behaviour.
Although women with insecure employment underwent the procedure knowing the
financial and physical implications of undergoing a major surgery, the future
health and work security afforded by hysterectomy appeared to them to outweigh
risks. Findings suggest that sterilization may be associated with an increased
risk of hysterectomy, potentially through biological or attitudinal links. Health
policy interventions require improved access to sexual and reproductive health
services and health education, along with surveillance and medical audits to
promote high-quality choices for women through the life cycle.
PMID- 27497140
TI - Sub-national health care financing reforms in Indonesia.
AB - Indonesia has seen an emergence of local health care financing schemes over the
last decade, implemented and operated by district governments. Often motivated by
the local political context and characterized by a large degree of heterogeneity
in scope and design, the common objective of the district schemes is to address
the coverage gaps for the informal sector left by national social health
insurance programs. This paper investigates the effect of these local health care
financing schemes on access to health care and financial protection. Using data
from a unique survey among District Health Offices, combined with data from the
annual National Socioeconomic Surveys, the study is based on a fixed effects
analysis for a panel of 262 districts over the period 2004-10, exploiting
variation in local health financing reforms across districts in terms of type of
reform and timing of implementation. Although the schemes had a modest impact on
average, they do seem to have provided some contribution to closing the coverage
gap, by increasing outpatient utilization for households in the middle quintiles
that tend to fall just outside the target population of the national subsidized
programs. However, there seems to be little effect on hospitalization or
financial protection, indicating the limitations of local health care financing
policies. In addition, we see effect heterogeneity across districts due to
differences in design features.
PMID- 27497141
TI - Prospective validation and adaptation of the HOSPITAL score to predict high risk
of unplanned readmission of medical patients.
AB - PRINCIPLES: The HOSPITAL score is a simple prediction model that accurately
identifies patients at high risk of readmission and showed good performance in an
international multicentre retrospective study. We aimed to demonstrate
prospectively its accuracy to predict 30-day unplanned readmission and death.
METHODS: We prospectively screened all consecutive patients aged >=50 years
admitted to the department of general internal medicine of a large community
hospital in Switzerland. We excluded patients who refused to give consent, who
died during hospitalisation, or who were transferred to another acute care,
rehabilitation or palliative care facility. The primary outcome was the first
unplanned readmission or death within 30 days after discharge. Some of the
predictors of the original score (discharge from an oncology service and length
of stay) were adapted according to the setting for practical reasons, before the
start of patient inclusion. We also assessed a simplified version of the score,
without the variable "any procedure performed during hospitalisation". The
performance of the score was evaluated according to its overall accuracy (Brier
score), its discriminatory power (C-statistic), and its calibration (Hosmer
Lemeshow goodness-of-fit test). RESULTS: Among the 346 included patients, 40
(11.6%) had a 30-day unplanned readmission or death. The HOSPITAL score showed
very good accuracy (Brier score 0.10), good discriminatory power (C-statistic
0.70, 95% confidence interval [CI] 0.62-0.79), and an excellent calibration (p =
0.77). Patients were classified into three risk categories for the primary
outcome: low (59%), intermediate (20.8%) and high risk (20.2%). The estimated
risks of unplanned readmission/death for each category were 8.2%, 11.3% and
21.6%, respectively. The simplified score showed the same performance, with a
Brier score of 0.10, a C-statistic of 0.70 (95% CI 0.61-0.79), and a goodness-of
fit statistic of 0.40. CONCLUSIONS: The HOSPITAL score prospectively identified
patients at high risk of 30-day unplanned readmission or death with good
performance in medical patients in Switzerland. Its simplicity and good
performance make it an easy-to-use tool to target patients who might most benefit
from intensive transitional care interventions.
PMID- 27497142
TI - Proposed cut-off value of the intrahepatic lipid content for metabolically normal
persons assessed by proton magnetic resonance spectroscopy in a Japanese
population.
AB - AIMS: To determine the threshold intrahepatic lipid (IHL) content separating
metabolically normal from abnormal in a Japanese population based on proton
magnetic resonance spectroscopy ((1)H-MRS). METHODS: A total of 305 Japanese
subjects aged 20-69years were investigated. The subjects underwent general
examination, blood tests, and (1)H-MRS of the liver after an overnight fast. They
completed a questionnaire about daily drinking habits and their daily alcohol
intake was calculated. RESULTS: The median IHL content was 4.7% in men and 1.7%
in women, and it increased along with the number of features of metabolic
syndrome (MetS). The optimum IHL cut-off value for separating normal subjects
from those with at least one feature of MetS was 6.5% in men (AUC of ROC: 0.727,
95%-CI: 0.649-0.804) and 1.8% in women (0.765, 0.685-0.844). Alcohol intake was
not correlated with the IHL content according to multiple logistic regression
analysis. CONCLUSION: This study demonstrated a close association of IHL with
features of MetS and identified IHL content cut-off values for metabolic
normality in Japanese subjects.
PMID- 27497143
TI - Detecting intrinsic muscle weakness of the hallux as an addition to early-stage
screening of the feet in patients with diabetes.
AB - AIMS: Present-day screening of the diabetic foot involves the Semmes Weinstein
Monofilament Test for evaluating loss of sensibility, while testing for intrinsic
muscle weakness is not implied. Just as with the early detection of sensibility
loss, early detection of intrinsic muscle weakness might have important
implications for the prevention of both ulceration and deformity in patients with
diabetes. The purpose of this study is to investigate the prevalence of patients
with diabetes presenting intrinsic muscle weakness of the hallux, but with a
normal sensibility of the sole of the foot. METHODS: A cross-sectional study
design was applied. Intrinsic muscle function of the hallux was measured with the
Paper Grip Test, while sensibility of the sole of the foot was measured with the
Semmes Weinstein Monofilament Test 5.07/10-g. RESULTS: In a period of three
months a total of 266 patients with diabetes (mean age 60, 134 females (50%), 177
type 2 diabetes mellitus (67%)) met the inclusion criteria and were examined for
both intrinsic muscle weakness of the hallux and sensibility of the soles of the
feet. The results showed that intrinsic muscle weakness was present more frequent
in patients with impaired sensibility (P=0.001), also 20% of the population had
intrinsic muscle weakness in the presence of normal sensibility. Multivariate
regression analysis showed that only age is associated with patients with
diabetes presenting normal sensibility but impaired intrinsic muscle function
(P=0.017). CONCLUSIONS: The Paper Grip Test could have added value to current
physical examination of the feet in patients with diabetes.
PMID- 27497144
TI - The local geographic distribution of diabetic complications in New York City:
Associated population characteristics and differences by type of complication.
AB - AIMS: To identify population characteristics associated with local variation in
the prevalence of diabetic complications and compare the geographic distribution
of different types of complications in New York City. METHODS: Using an all-payer
database of emergency visits, we identified the proportion of unique adults with
diabetes who also had cardiac, neurologic, renal and lower extremity
complications. We performed multivariable regression to identify associations of
demographic and socioeconomic factors, and diabetes-specific emergency department
use with the prevalence of diabetic complications by Census tract. We also used
geospatial analysis to compare local hotspots of diabetic complications. RESULTS:
We identified 4.6million unique New York City adults, of which 10.5% had
diabetes. Adjusting for demographic and socioeconomic factors, diabetes-specific
emergency department use was associated with severe microvascular renal and lower
extremity complications (p-values<0.001), but not with severe macrovascular
cardiac or neurologic complications (p-values of 0.39 and 0.29). Our hotspot
analysis demonstrated significant geographic heterogeneity in the prevalence of
diabetic complications depending on the type of complication. Notably, the
geographic distribution of hotspots of myocardial infarction were inversely
correlated with hotspots of end-stage renal disease and lower extremity
amputations (coefficients: -0.28 and -0.28). CONCLUSIONS: We found differences in
the local geographic distribution of diabetic complications, which highlight the
contrasting risk factors for developing macrovascular versus microvascular
diabetic complications. Based on our analysis, we also found that high diabetes
specific emergency department use was correlated with poor diabetic outcomes.
Emergency department utilization data can help identify the location of specific
populations with poor glycemic control.
PMID- 27497145
TI - Cultural issues and other factors that affect self-management of Type 2 Diabetes
Mellitus (T2D) by Chinese immigrants in Australia.
AB - AIMS: To investigate the influence of cultural and other factors on diabetes self
management behaviors among Australian Chinese immigrants with T2D. METHODS: A
cross-sectional survey was conducted between June and October 2015. The
questionnaire comprised several validated scales examining aspects of self
management practice including medication adherence, acculturation and
demographics. Participants were recruited from the community and Diabetes Center
of the Royal Prince Alfred Hospital (RPAH), Sydney, Australia. RESULTS: Of the
139 participants, a majority were female, from mainland China, with high school
level education and a mean age of 64 (SD+/-12) years. Participants were found to
have poor self-management practices generally but moderate medication adherence.
13.7% of participants reported incorporating TCM into their diabetes treatment
and 24% reported a cultural shame surrounding a diabetes diagnosis. Higher levels
of acculturation predicted better medication adherence, whereas stronger beliefs
in TCM predicted poorer medication adherence. Gender, education level and
duration of diabetes were also predictors of diabetes self-management behaviors.
CONCLUSIONS: This study provided insight into cultural influences on diabetes
self-management and medication taking among Chinese immigrants in Australia.
Health care providers should take these into account in delivering culturally
sensitive care and advice to achieve better health outcomes.
PMID- 27497146
TI - Expression and correlation of sex hormone-binding globulin and insulin signal
transduction and glucose transporter proteins in gestational diabetes mellitus
placental tissue.
AB - OBJECTIVE: The aim of the present study was to investigate the probable
pathogenesis of gestational diabetes mellitus (GDM) by analyzing the correlation
between sex hormone-binding globulin (SHBG) secreted by the placenta during
pregnancy and insulin signaling components and glucose transporter proteins
(GLUTs) in the placental tissue. DESIGN AND METHODS: Placental tissue was
collected from full-term and non-obese [body mass index <25kg/m(2)] pregnant
women; 10 diagnosed with GDM and 10 with normal pregnancy. We used real-time
polymerase chain reaction (PCR), immunohistochemistry and western blotting to
detect expression of protein and mRNA of SHBG and insulin signaling components
and GLUTs in placental tissue. RESULTS: In the placental tissue of non-obese
women, there was a decrease in expression of SHBG protein and mRNA, with a
concurrent decrease in expression of GLUT-4 protein and mRNA in women with GDM
compared with normal controls. There was a decrease in GLUT-3 and insulin
receptor substrate (IRS)-1 protein expression and lower IRS-2 mRNA expression was
also observed in GDM placental tissue. Linear correlation analyses showed a
positive correlation between SHBG and IRS-2 mRNA (P=0.038, R(2)=0.2178,
y=0.249x+1.4208); positive correlation between SHBG and phosphatidylinositol 3
kinase (PI3K) p85alpha mRNA (P=0.035, R(2)=0.224, y=0.3506x+0.7433); positive
correlation between SHBG and GLUT-4 mRNA (P=0.000, R(2)=0.5174,
y=1.3822+1.7811x); positive correlation between IRS-2 and GLUT-4 mRNA (P=0.002,
R(2)=0.4064, y=-0.8272+2.9592x); negative correlation between IRS-1 and PI3K
p85alpha mRNA (P=0.005, R(2)=0.366, y=2.4492-0.1929x); negative correlation
between IRS-1 and GLUT-3 mRNA (P=0.027, R(2)=0.243, y=0.9254-0.0714x); and
positive correlation between IRS-2 and GLUT-1 mRNA (P=0.004, R(2)=0.3794,
y=0.0225+0.6298x). CONCLUSION: The results confirm that defective receptors for
insulin signal transduction and GLUT proteins are present in GDM placental
tissue. Decreasing expression of SHBG may participate in regulation of insulin
signaling, leading to a concomitant decrease in expression of relevant insulin
signaling components in placental tissue, implying insulin resistance and
eventual development of GDM.
PMID- 27497147
TI - Nutrition and Diabetes.
PMID- 27497148
TI - Excess Omega-6 Polyunsaturated Fatty Acid Intake Is Associated with Negative
Cardiovascular, Intestinal and Metabolic Outcomes in Mice.
PMID- 27497149
TI - Sickeningly Sweet: Does Sugar Cause Chronic Disease? No.
PMID- 27497150
TI - Review of Dietary Practices of the 21st Century: Facts and Fallacies.
AB - The prevalence of chronic metabolic diseases, such as diabetes, cardiovascular
diseases and cancer, is increasing around the world. Nutritional interventions
can reduce the prevalence and provide effective treatment, even when weight loss
is not dramatic. The 2013 Canadian Diabetes Association Clinical Practice
Guidelines concluded that certain dietary patterns and popular weight-loss diets
had sufficient evidence to suggest their use by individuals with diabetes, but
many other diet patterns and diets exist. Our specific objectives were to review
the nutritional quality of various dietary patterns and diets, with emphasis on
the evidence that they are efficacious for weight loss, glycemic control and
cardiovascular risk factors.
PMID- 27497151
TI - The Role of Pulses in the Dietary Management of Diabetes.
AB - Pulses are highly nutritious foods that are included as part of Canada's Food
Guide to promote healthful eating, and they have established health benefits that
can contribute to the dietary management of diabetes. A review of studies that
have examined the effects of pulse consumption on health outcomes, integral to
the management of diabetes, provides credible evidence for improvements in
glycemic control, reduction of blood lipids and regulation of body weight.
Results from acute feeding trials suggest that postprandial blood glucose
response is significantly attenuated by a single pulse serving of between three
quarters and 1 cup. At lower doses, pulses attenuate postprandial blood glucose
response more than similar amounts of starchy foods. Long-term pulse consumption
of 5 cups per week appears to result consistently in improvements in glycemic
control. There is high-quality evidence that supports a role for pulse
consumption in the reduction of risk for cardiovascular disease; this provides a
sound rationale for the regular incorporation of pulses at about two-thirds of a
cup daily in the management of hyperlipidemia in persons with type 2 diabetes.
Pulse consumption can contribute to improving satiety, reducing food intake and
regulating body weight, which can reduce obesity risk and, in turn, improve
diabetes management. Collectively, available evidence provides very good support
for a role of regular pulse consumption in the prevention and management of
diabetes.
PMID- 27497152
TI - Polymorphism of the phosphoserine phosphatase gene in Streptococcus thermophilus
and its potential use for typing and monitoring of population diversity.
AB - The phosphoserine phosphatase gene (serB) of Streptococcus thermophilus is the
most polymorphic gene among those used in Multilocus Sequence Typing schemes for
this species and has been used for both genotyping of isolates and for evaluation
of population diversity. However, the information on the potential of this gene
as a marker for diversity in S. thermophilus species is still fragmentary. In
this study, we evaluated serB nucleotide polymorphism and its potential impact on
protein structure using data from traditional sequencing. In addition we
evaluated the ability of serB targeted high-throughput sequencing in studying the
diversity of S. thermophilus populations in cheese and starter cultures. Data
based on traditional cultivation based techniques and sequencing provided
evidence that the distribution of serB alleles varies significantly in some
environments (commercial starter cultures, traditional starter cultures, cheese).
Mutations had relatively little impact on predicted protein structure and were
not found in domains that are predicted to be important for its functionality.
Cultivation independent, serB targeted high-throughput sequencing provided
evidence for significantly different alleles distribution in different cheese
types and detected fluctuations in alleles abundance in a mixed strain starter
reproduced by backslopping. Notwithstanding some shortcomings of this method that
are discussed here, the cultivation independent approach appears to be more
sensitive than cultivation based approaches based on isolation and traditional
sequencing.
PMID- 27497154
TI - The relationship between 63days of 24-h urinary free cortisol and hair cortisol
levels in 10 healthy individuals.
AB - BACKGROUND: Interest in measuring cortisol in scalp hair is increasing because of
its assumed ability to provide a historical timeline of previous systemic levels
of cortisol. Yet, it remains uncertain how well hair cortisol represents the
total systemic secretion of cortisol over time. METHODS: Ten healthy individuals
collected 24-h urine samples for 63 consecutive days and provided a hair sample
at the end of the study period. 24-h urinary creatinine levels in every urine
sample were determined to assess completeness of the samples. Cortisol levels in
24-h urine samples and in hair were measured with liquid chromatography tandem
mass spectrometry. The correlations between urinary cortisol and hair cortisol
were calculated using Kendall's tau. RESULTS: We found a nonsignificant moderate
correlation between average urinary cortisol secretion and average hair cortisol
concentration rt=0.422, p=0.089. CONCLUSIONS: Hair cortisol concentration
correlates low to moderately with 24-h urinary cortisol concentration over a
period of 63days.
PMID- 27497153
TI - Corticotropin-releasing hormone receptor 1 (CRH-R1) polymorphisms are associated
with irritable bowel syndrome and acoustic startle response.
AB - BACKGROUND: Corticotropin-releasing hormone receptor 1 (CRH-R1) in the amygdala
and the stria terminalis plays an important role in the activation of central
stress circuits. Genetic factors may contribute to the hyperresponsiveness of
these circuits in irritable bowel syndrome (IBS). AIMS: To determine if CRH-R1
SNPs are associated with: (1) a diagnosis of IBS, (2) gastrointestinal (GI)
symptoms, and (3) acoustic startle response (ASR) to threat, which is mediated by
the amygdala via CRH. METHODS: Three CRH-R1 SNPS (rs110402, rs242924, and
rs7209436) were genotyped using salivary DNA from IBS and healthy control
subjects (HCs). Eye blink ASR was obtained during safe (no shock), anticipation
(abdominal shock may soon occur) and threat (abdominal shock likely) conditions
in a subset of subjects. Associations between each SNP with IBS status, clinical
traits and ASR were measured. RESULTS: 235 IBS patients (mean age 37.5 yrs, 74%
F) and 264 HCs (mean age 32.1 yrs, 70% F) were studied. Of these, 57 IBS and 41
HCs underwent the ASR protocol. The presence of IBS was associated with the major
allele for all three CRH-R1 SNPs (p=0.009-0.025). Within IBS, the major allele
for all three SNPs (p=0.017-0.065) was associated with GI symptom anxiety scores.
Within subjects with at least one copy of the major allele for the CRH-R1 SNPs,
IBS had significantly lower ASR compared to HCs during threat conditions (p=0.001
0.002). Within IBS, CRH-R1 SNPs were associated with a graded increase in ASR to
threat (p=0.007-0.008). CONCLUSION: These findings support that CRH-R1
contributes to the dysregulated stress responsiveness in IBS.
PMID- 27497155
TI - Progranulin is increased in human and murine lipodystrophy.
AB - AIMS: Lipodystrophies (LD) are genetic or acquired disorders sharing the symptom
of partial or complete adipose tissue deficiency and a dysregulation of
adipokines including leptin and adiponectin. Progranulin, an adipokine with
proinflammatory and insulin resistance-inducing characteristics, has not been
investigated in LD so far. METHODS: Circulating progranulin was determined in LD
patients (N=37) and in age-, gender-, and body mass index-matched healthy control
subjects (N=37). Additionally, we investigated progranulin expression in an LD
mouse model as compared to wild-type mice. Moreover, we elucidated circulating
progranulin before and during metreleptin supplementation in 10 patients with LD.
RESULTS: Median [interquartile range] circulating progranulin was increased in
patients with LD (82.9 [25.9] MUg/l) as compared to controls (73.6 [22.8] MUg/l)
(p=0.005). C-reactive protein (CRP) remained an independent and positive
predictor of progranulin in multivariate analysis. Progranulin mRNA was
significantly upregulated in all adipose tissue depots, i.e. visceral,
subcutaneous, and brown adipose tissue, and in muscle of LD animals versus wild
type mice. Progranulin levels did not significantly change during metreleptin
supplementation. CONCLUSIONS: Progranulin serum concentration is increased in
patients with LD, and shows an independent and positive correlation with CRP.
Different adipose tissue depots and muscle might be potential origins of elevated
progranulin.
PMID- 27497156
TI - Liquid chromatography-tandem mass spectrometric analysis of ten estrogen
metabolites at sub-picogram levels in breast cancer women.
AB - The measurement of estrogens at sub-picogram levels is essential for research on
breast cancer and postmenopausal plasma. Heretofore, these concentration levels
have rarely been achieved. However, it is possible through derivatization but
still represent problems for monitoring catechol estrogens and 16alpha
hydroxyestrone (16alpha-OH-E1). Estrogens possess poor ionization efficiency in
MS/MS, which results in insufficient sensitivity for analyzing samples at trace
concentrations. The method presented here was used to extract ten estrogen
metabolites (EMs) with a derivatization step involving a new adduct. The
electrospray ionization (ESI) MS/MS sensitivity for the EMs was enhanced by
derivatization with 3-bromomethyl-propyphenazone (BMP). The lower limits of
quantification (LLOQ) of the EMs were 12-100 femtogram on-column, equivalent to
0.3-3.6pg/mL plasma, and the limits of detection (LOD) were 0.1-0.8pg/mL plasma.
The percentage coefficient of variation (CV%) at the LLOQ was <20 for all
investigated EMs. Ionization suppression was minimized by reacting the excess
reagent, BMP, with methanol. The method was successfully applied for the
determination of ten EMs in the plasma of fifty healthy postmenopausal and fifty
ductal breast cancer women aged 47-65 years old. 16alpha-OH-E1 and three catechol
estrogen metabolites, 4-OH-E1, 2-OH-E2 and 4-OH-E2, were successfully measured in
the plasma of healthy and breast cancer women. The methyl-propyphenazone-EM
derivatives exhibited better sensitivity in ESI-MS (7.5-fold) compared to the
commonly used dansylation procedure.
PMID- 27497157
TI - Simultaneous determination of eugenol, isoeugenol and methyleugenol in fish
fillet using gas chromatography coupled to tandem mass spectrometry.
AB - Gas chromatography (GC) coupled with triple quadrupole tandem mass spectrometry
(MS/MS) operated in electron ionization mode (EI) has been shown to have
advantages in the trace analysis of chemical compounds. Employing the instrument,
a method has been built to simultaneously determine eugenol, isoeugenol' and
methyleugenol, which have been widely used as fish anesthetic, in the fish
fillet. Procedure for the sample preparation was achieved by using hexane
extraction followed by phenyl solid phase extraction (SPE) cleanup, which was
free of such steps as rotary evaporation and nitrogen blowing by taking the
volatility of eugenol and its isomers into consideration. The method was
validated by conducting recovery studies on fortified fish fillet samples at four
concentrations. The linearity in the range of 5-500MUg.L(-1) was forced through
the origin giving a coefficient of determination (r(2)) greater than 0.9982.
Limits of detection (LODs) for eugenol, isoeugenol' and methyleugenol were 0.4,
1.2' and 0.2MUg.kg(-1), respectively. The limits of quantification (LOQs) were
1.2, 4' and 0.7MUg.kg(-1) for eugenol, isoeugenol' and methyleugenol,
respectively. The recoveries for eugenol and its isomers ranged from 76.4 to
99.9% with relative standard deviations (RSD) in a range from 2.18 to 15.5%. This
method is quick, simple and suitable for determining the residues of eugenol,
isoeugenol and methyleugenol simultaneously in batch samples of fish fillet.
PMID- 27497158
TI - Micro RNA-19a suppresses IL-10 in peripheral B cells from patients with
atherosclerosis.
AB - BACKGROUND AND AIMS: The interleukin (IL)-10-production B cells play an important
role in the pathogenesis of atherosclerosis (Asro) with unknown mechanism. Micro
RNA (miR)-17-92 cluster has strong immune regulatory activities. This study tests
a hypothesis that miR-17-92 cluster suppresses IL-10 expression in B cells of
Asro patients. METHODS: Patients with Asro were recruited into this study.
Peripheral blood samples were collected from the patients. B cells were isolated
from the blood samples and analyzed to elucidate the role of miR-17-92 in the
regulation of IL-10 expression. RESULTS: Peripheral B cells from patients with
Asro show lower levels of IL-10 than that from healthy subjects. The IL-10
expression in the B cells is negatively correlated with the expression of miR-19a
in the B cells. The serum levels of tumor necrosis factor (TNF)-alpha, interferon
(IFN)-gamma and interleukin (IL)-4 in Asro patients were higher than healthy
subjects. Exposure to TNF-alpha or IFN-gamma or IL-4 suppressed IL-10 expression
in B cells via increasing the expression of miR-19a in B cells, which could be
abolished by Inhibition of miR-19a. CONCLUSIONS: TNF-alpha or IFN-gamma or IL-4
suppresses IL-10 in B cells via up regulating miR-19a expression.
PMID- 27497159
TI - Anti cytokine therapy in chronic inflammatory arthritis.
AB - This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA),
Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores
the similarities and differences in the clinical features, as well as treatments
and cytokines involved in the development and propagation of the disease.
Particular attention is paid to TNFalpha inhibitors IL-1ra, IL-6 and JAK kinase
Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17.
PMID- 27497160
TI - Continuum Electrostatics Approaches to Calculating pKas and Ems in Proteins.
AB - Proteins change their charge state through protonation and redox reactions as
well as through binding charged ligands. The free energy of these reactions is
dominated by solvation and electrostatic energies and modulated by protein
conformational relaxation in response to the ionization state changes. Although
computational methods for calculating these interactions can provide very
powerful tools for predicting protein charge states, they include several
critical approximations of which users should be aware. This chapter discusses
the strengths, weaknesses, and approximations of popular computational methods
for predicting charge states and understanding the underlying electrostatic
interactions. The goal of this chapter is to inform users about applications and
potential caveats of these methods as well as outline directions for future
theoretical and computational research.
PMID- 27497161
TI - Path Sampling Methods for Enzymatic Quantum Particle Transfer Reactions.
AB - The mechanisms of enzymatic reactions are studied via a host of computational
techniques. While previous methods have been used successfully, many fail to
incorporate the full dynamical properties of enzymatic systems. This can lead to
misleading results in cases where enzyme motion plays a significant role in the
reaction coordinate, which is especially relevant in particle transfer reactions
where nuclear tunneling may occur. In this chapter, we outline previous methods,
as well as discuss newly developed dynamical methods to interrogate mechanisms of
enzymatic particle transfer reactions. These new methods allow for the
calculation of free energy barriers and kinetic isotope effects (KIEs) with the
incorporation of quantum effects through centroid molecular dynamics (CMD) and
the full complement of enzyme dynamics through transition path sampling (TPS).
Recent work, summarized in this chapter, applied the method for calculation of
free energy barriers to reaction in lactate dehydrogenase (LDH) and yeast alcohol
dehydrogenase (YADH). We found that tunneling plays an insignificant role in YADH
but plays a more significant role in LDH, though not dominant over classical
transfer. Additionally, we summarize the application of a TPS algorithm for the
calculation of reaction rates in tandem with CMD to calculate the primary H/D KIE
of YADH from first principles. We found that the computationally obtained KIE is
within the margin of error of experimentally determined KIEs and corresponds to
the KIE of particle transfer in the enzyme. These methods provide new ways to
investigate enzyme mechanism with the inclusion of protein and quantum dynamics.
PMID- 27497162
TI - Accurate Calculation of Electric Fields Inside Enzymes.
AB - The specific electric field generated by a protease at its active site is
considered as an important source of the catalytic power. Accurate calculation of
electric field at the active site of an enzyme has both fundamental and practical
importance. Measuring site-specific changes of electric field at internal sites
of proteins due to, eg, mutation, has been realized by using molecular probes
with CO or CN groups in the context of vibrational Stark effect. However,
theoretical prediction of change in electric field inside a protein based on a
conventional force field, such as AMBER or OPLS, is often inadequate. For such
calculation, quantum chemical approach or quantum-based polarizable or polarized
force field is highly preferable. Compared with the result from conventional
force field, significant improvement is found in predicting experimentally
measured mutation-induced electric field change using quantum-based methods,
indicating that quantum effect such as polarization plays an important role in
accurate description of electric field inside proteins. In comparison, the best
theoretical prediction comes from fully quantum mechanical calculation in which
both polarization and inter-residue charge transfer effects are included for
accurate prediction of electrostatics in proteins.
PMID- 27497163
TI - Molecular Dynamics Studies of Proton Transport in Hydrogenase and Hydrogenase
Mimics.
AB - There is extensive interest in hydrogenases based on their ability to rapidly and
efficiently interconvert H2 with protons and electrons, and their (typically)
superior function relative to molecular mimics. Understanding the function of
enzymes is one approach to implementing design features to make better catalysts
and is an approach we have implemented in our work. In this review, we will
discuss our efforts to develop design principles from enzymes, with specific
focus on proton transport. We will also present computational studies of the
mimics we have investigated with similar methodologies. We will discuss the
mechanisms used by small scaffolds on molecular mimics which in many cases are
surprisingly similar to those used by nature, while in other cases, computational
analysis allowed us to reveal an unexpected role. Computational methods provide
one of the best ways, and in some cases, the only way, to gain insight into the
mechanistic details of enzymes. In this review, we illustrate the general
computational strategy we used to study the proton pathway of [FeFe]-hydrogenase,
and the similar strategy to investigate small molecules. We present the main
results we obtained and how our computational work stimulated or worked in
concert with experimental investigations. We also focus on estimation of errors
and convergence of properties in the simulations. These studies demonstrate the
powerful results that can be obtained by the close pairing of experimental and
theoretical approaches.
PMID- 27497164
TI - Modeling Mercury in Proteins.
AB - Mercury (Hg) is a naturally occurring element that is released into the biosphere
both by natural processes and anthropogenic activities. Although its reduced,
elemental form Hg(0) is relatively nontoxic, other forms such as Hg(2+) and, in
particular, its methylated form, methylmercury, are toxic, with deleterious
effects on both ecosystems and humans. Microorganisms play important roles in the
transformation of mercury in the environment. Inorganic Hg(2+) can be methylated
by certain bacteria and archaea to form methylmercury. Conversely, bacteria also
demethylate methylmercury and reduce Hg(2+) to relatively inert Hg(0).
Transformations and toxicity occur as a result of mercury interacting with
various proteins. Clearly, then, understanding the toxic effects of mercury and
its cycling in the environment requires characterization of these interactions.
Computational approaches are ideally suited to studies of mercury in proteins
because they can provide a detailed molecular picture and circumvent issues
associated with toxicity. Here, we describe computational methods for
investigating and characterizing how mercury binds to proteins, how inter- and
intraprotein transfer of mercury is orchestrated in biological systems, and how
chemical reactions in proteins transform the metal. We describe quantum chemical
analyses of aqueous Hg(II), which reveal critical factors that determine ligand
binding propensities. We then provide a perspective on how we used chemical
reasoning to discover how microorganisms methylate mercury. We also highlight our
combined computational and experimental studies of the proteins and enzymes of
the mer operon, a suite of genes that confer mercury resistance in many bacteria.
Lastly, we place work on mercury in proteins in the context of what is needed for
a comprehensive multiscale model of environmental mercury cycling.
PMID- 27497165
TI - Steered Molecular Dynamics Methods Applied to Enzyme Mechanism and Energetics.
AB - One of the main goals of chemistry is to understand the underlying principles of
chemical reactions, in terms of both its reaction mechanism and the
thermodynamics that govern it. Using hybrid quantum mechanics/molecular mechanics
(QM/MM)-based methods in combination with a biased sampling scheme, it is
possible to simulate chemical reactions occurring inside complex environments
such as an enzyme, or aqueous solution, and determining the corresponding free
energy profile, which provides direct comparison with experimental determined
kinetic and equilibrium parameters. Among the most promising biasing schemes is
the multiple steered molecular dynamics method, which in combination with
Jarzynski's Relationship (JR) allows obtaining the equilibrium free energy
profile, from a finite set of nonequilibrium reactive trajectories by
exponentially averaging the individual work profiles. However, obtaining
statistically converged and accurate profiles is far from easy and may result in
increased computational cost if the selected steering speed and number of
trajectories are inappropriately chosen. In this small review, using the
extensively studied chorismate to prephenate conversion reaction, we first
present a systematic study of how key parameters such as pulling speed, number of
trajectories, and reaction progress are related to the resulting work
distributions and in turn the accuracy of the free energy obtained with JR.
Second, and in the context of QM/MM strategies, we introduce the Hybrid
Differential Relaxation Algorithm, and show how it allows obtaining more accurate
free energy profiles using faster pulling speeds and smaller number of
trajectories and thus smaller computational cost.
PMID- 27497166
TI - New Algorithms for Global Optimization and Reaction Path Determination.
AB - We present new schemes to improve the convergence of an important global
optimization problem and to determine reaction pathways (RPs) between identified
minima. Those methods have been implemented into the CAST program (Conformational
Analysis and Search Tool). The first part of this chapter shows how to improve
convergence of the Monte Carlo with minimization (MCM, also known as Basin
Hopping) method when applied to optimize water clusters or aqueous solvation
shells using a simple model. Since the random movement on the potential energy
surface (PES) is an integral part of MCM, we propose to employ a hydrogen bonding
based algorithm for its improvement. We show comparisons of the results obtained
for random dihedral and for the proposed random, rigid-body water molecule
movement, giving evidence that a specific adaption of the distortion process
greatly improves the convergence of the method. The second part is about the
determination of RPs in clusters between conformational arrangements and for
reactions. Besides standard approaches like the nudged elastic band method, we
want to focus on a new algorithm developed especially for global reaction path
search called Pathopt. We started with argon clusters, a typical benchmark
system, which possess a flat PES, then stepwise increase the magnitude and
directionality of interactions. Therefore, we calculated pathways for a water
cluster and characterize them by frequency calculations. Within our calculations,
we were able to show that beneath local pathways also additional pathways can be
found which possess additional features.
PMID- 27497167
TI - Simulation Studies of Protein and Small Molecule Interactions and Reaction.
AB - Computational studies of protein and small molecule (protein-ligand/enzyme
substrate) interactions become more and more important in biological science and
drug discovery. Computer modeling can provide molecular details of the processes
such as conformational change, binding, and transportation of small
molecules/proteins, which are not easily to be captured in experiments. In this
chapter, we discussed simulation studies of both protein and small molecules from
three aspects: conformation sampling, transportations of small molecules in
enzymes, and enzymatic reactions involving small molecules. Both methodology
developments and examples of simulation studies in this field were presented.
PMID- 27497168
TI - How to Run FAST Simulations.
AB - Molecular dynamics (MD) simulations are a powerful tool for understanding
enzymes' structures and functions with full atomistic detail. These physics-based
simulations model the dynamics of a protein in solution and store snapshots of
its atomic coordinates at discrete time intervals. Analysis of the snapshots from
these trajectories provides thermodynamic and kinetic properties such as
conformational free energies, binding free energies, and transition times.
Unfortunately, simulating biologically relevant timescales with brute force MD
simulations requires enormous computing resources. In this chapter we detail a
goal-oriented sampling algorithm, called fluctuation amplification of specific
traits, that quickly generates pertinent thermodynamic and kinetic information by
using an iterative series of short MD simulations to explore the vast depths of
conformational space.
PMID- 27497169
TI - Bridging Enzymatic Structure Function via Mechanics: A Coarse-Grain Approach.
AB - Flexibility is a central aspect of protein function, and ligand binding in
enzymes involves a wide range of structural changes, ranging from large-scale
domain movements to small loop or side-chain rearrangements. In order to
understand how the mechanical properties of enzymes, and the mechanical
variations that are induced by ligand binding, relate to enzymatic activity, we
carried out coarse-grain Brownian dynamics simulations on a set of enzymes whose
structures in the unbound and ligand-bound forms are available in the Protein
Data Bank. Our results show that enzymes are remarkably heterogeneous objects
from a mechanical point of view and that the local rigidity of individual
residues is tightly connected to their part in the protein's overall structure
and function. The systematic comparison of the rigidity of enzymes in their
unbound and bound forms highlights the fact that small conformational changes can
induce large mechanical effects, leading to either more or less flexibility
depending on the enzyme's architecture and the location of its ligand-biding
site. These mechanical variations target a limited number of specific residues
that occupy key locations for enzymatic activity, and our approach thus offers a
mean to detect perturbation-sensitive sites in enzymes, where the addition or
removal of a few interactions will lead to important changes in the proteins
internal dynamics.
PMID- 27497170
TI - A Networks Approach to Modeling Enzymatic Reactions.
AB - Modeling enzymatic reactions is a demanding task due to the complexity of the
system, the many degrees of freedom involved and the complex, chemical, and
conformational transitions associated with the reaction. Consequently, enzymatic
reactions are not determined by precisely one reaction pathway. Hence, it is
beneficial to obtain a comprehensive picture of possible reaction paths and
competing mechanisms. By combining individually generated intermediate states and
chemical transition steps a network of such pathways can be constructed.
Transition networks are a discretized representation of a potential energy
landscape consisting of a multitude of reaction pathways connecting the end
states of the reaction. The graph structure of the network allows an easy
identification of the energetically most favorable pathways as well as a number
of alternative routes.
PMID- 27497171
TI - Conformational Sub-states and Populations in Enzyme Catalysis.
AB - Enzyme function involves substrate and cofactor binding, precise positioning of
reactants in the active site, chemical turnover, and release of products. In
addition to formation of crucial structural interactions between enzyme and
substrate(s), coordinated motions within the enzyme-substrate complex allow
reaction to proceed at a much faster rate, compared to the reaction in solution
and in the absence of enzyme. An increasing number of enzyme systems show the
presence of conserved protein motions that are important for function. A wide
variety of motions are naturally sampled (over femtosecond to millisecond time
scales) as the enzyme complex moves along the energetic landscape, driven by
temperature and dynamical events from the surrounding environment. Areas of low
energy along the landscape form conformational sub-states, which show higher
conformational populations than surrounding areas. A small number of these
protein conformational sub-states contain functionally important structural and
dynamical features, which assist the enzyme mechanism along the catalytic cycle.
Identification and characterization of these higher-energy (also called excited)
sub-states and the associated populations are challenging, as these sub-states
are very short-lived and therefore rarely populated. Specialized techniques based
on computer simulations, theoretical modeling, and nuclear magnetic resonance
have been developed for quantitative characterization of these sub-states and
populations. This chapter discusses these techniques and provides examples of
their applications to enzyme systems.
PMID- 27497172
TI - Computation of Rate Constants for Diffusion of Small Ligands to and from Buried
Protein Active Sites.
AB - The diffusion of ligands to actives sites of proteins is essential to enzyme
catalysis and many cellular signaling processes. In this contribution we review
our recently developed methodology for calculation of rate constants for
diffusion and binding of small molecules to buried protein active sites. The
diffusive dynamics of the ligand obtained from molecular dynamics simulation is
coarse grained and described by a Markov state model. Diffusion and binding rate
constants are then obtained either from the reactive flux formalism or by fitting
the time-dependent population of the Markov state model to a phenomenological
rate law. The method is illustrated by applications to diffusion of substrate and
inhibitors in [NiFe] hydrogenase, CO-dehydrogenase, and myoglobin. We also
discuss a recently developed sensitivity analysis that allows one to identify hot
spots in proteins, where mutations are expected to have the strongest effects on
ligand diffusion rates.
PMID- 27497173
TI - Calculation of Enzyme Fluctuograms from All-Atom Molecular Dynamics Simulation.
AB - In this work, a computational framework is presented to compute the time
evolution of force constants for a coarse grained (CG) elastic network model
along an all-atom molecular dynamics trajectory of a protein system. Obtained via
matching distance fluctuations, these force constants represent strengths of
mechanical coupling between CG beads. Variation of coupling strengths with time
is hence termed the fluctuogram of protein dynamics. In addition to the schematic
procedure and implementation considerations, several ways of combining force
constants and data analysis are presented to illustrate the potential application
of protein fluctuograms. The unique angle provided by the fluctuogram expands the
scope of atomistic simulations and is expected to impact upon fundamental
understanding of protein dynamics as well as protein engineering technologies.
PMID- 27497174
TI - Constructing Kinetic Network Models to Elucidate Mechanisms of Functional
Conformational Changes of Enzymes and Their Recognition with Ligands.
AB - Enzymes are biological macromolecules that catalyze complex reactions in life. In
order to perform their functions effectively and efficiently, enzymes undergo
conformational changes between different functional states. Therefore,
elucidating the dynamics between these states is essential to understand the
molecular mechanisms of enzymes. Although experimental methods such as X-ray
crystallography and cryoelectron microscopy can produce high-resolution
structures, the detailed conformational dynamics of many enzymes still remain
obscure. While molecular dynamics (MD) simulations are able to complement the
experiments by providing structure-based dynamics at atomic resolution, it is
usually difficult for them to reach the biologically relevant timescales
(hundreds of microseconds or longer). Kinetic network models (KNMs), in
particular Markov state models (MSMs), hold great promise to overcome this
challenge because they can bridge the timescale gap between MD simulations and
experimental observations. In this chapter, we review the procedure of
constructing KNMs to elucidate the molecular mechanisms of enzymes. First, we
will give a general introduction of MSMs, including the methods to construct and
validate MSMs. Second, we will present the applications of KNMs to study two
important enzymes: the human Argonaute protein and the RNA polymerase II. We
conclude by discussing the future perspectives regarding the potential of KNMs to
investigate the dynamics of enzymes' functional conformational changes.
PMID- 27497175
TI - Microscopic Characterization of Membrane Transporter Function by In Silico
Modeling and Simulation.
AB - Membrane transporters mediate one of the most fundamental processes in biology.
They are the main gatekeepers controlling active traffic of materials in a highly
selective and regulated manner between different cellular compartments demarcated
by biological membranes. At the heart of the mechanism of membrane transporters
lie protein conformational changes of diverse forms and magnitudes, which closely
mediate critical aspects of the transport process, most importantly the
coordinated motions of remotely located gating elements and their tight coupling
to chemical processes such as binding, unbinding and translocation of transported
substrate and cotransported ions, ATP binding and hydrolysis, and other molecular
events fueling uphill transport of the cargo. An increasing number of functional
studies have established the active participation of lipids and other components
of biological membranes in the function of transporters and other membrane
proteins, often acting as major signaling and regulating elements. Understanding
the mechanistic details of these molecular processes require methods that offer
high spatial and temporal resolutions. Computational modeling and simulations
technologies empowered by advanced sampling and free energy calculations have
reached a sufficiently mature state to become an indispensable component of
mechanistic studies of membrane transporters in their natural environment of the
membrane. In this article, we provide an overview of a number of major
computational protocols and techniques commonly used in membrane transporter
modeling and simulation studies. The article also includes practical hints on
effective use of these methods, critical perspectives on their strengths and weak
points, and examples of their successful applications to membrane transporters,
selected from the research performed in our own laboratory.
PMID- 27497177
TI - Preface.
PMID- 27497176
TI - Detecting Allosteric Networks Using Molecular Dynamics Simulation.
AB - Allosteric networks allow enzymes to transmit information and regulate their
catalytic activities over vast distances. In principle, molecular dynamics (MD)
simulations can be used to reveal the mechanisms that underlie this phenomenon;
in practice, it can be difficult to discern allosteric signals from MD
trajectories. Here, we describe how MD simulations can be analyzed to reveal
correlated motions and allosteric networks, and provide an example of their use
on the coagulation enzyme thrombin. Methods are discussed for calculating residue
pair correlations from atomic fluctuations and mutual information, which can be
combined with contact information to identify allosteric networks and to
dynamically cluster a system into highly correlated communities. In the case of
thrombin, these methods show that binding of the antagonist hirugen significantly
alters the enzyme's correlation landscape through a series of pathways between
Exosite I and the catalytic core. Results suggest that hirugen binding curtails
dynamic diversity and enforces stricter venues of influence, thus reducing the
accessibility of thrombin to other molecules.
PMID- 27497178
TI - Editorial Comment.
PMID- 27497179
TI - Editorial Comment.
PMID- 27497180
TI - Editorial Comment.
PMID- 27497181
TI - Comparison between the indocyanine green fluorescence and blue dye methods for
sentinel lymph node biopsy using novel fluorescence image-guided resection
equipment in different types of hospitals.
AB - Sentinel lymph node biopsy (SLNB) has become a standard of care to detect
axillary lymph metastasis in early-stage breast cancer patients with clinically
negative axillary lymph nodes. Current SLNB detection modalities comprising a
blue dye, a radioactive tracer, or a combination of both have advantages as well
as disadvantages. Thus, near-infrared fluorescence imaging using indocyanine
green (ICG) has recently been regarded as a novel method that has generated
interest for SLNB around the world. However, the lack of appropriate fluorescence
imaging systems has hindered further research and wide application of this
method. Therefore, we developed novel fluorescence image-guided resection
equipment (FIRE) to detect sentinel lymph nodes (SLNs). Moreover, to compare the
ICG fluorescence imaging method with the blue dye method and to explore the
universal feasibility of the former, a different type of hospital study was
conducted. Ninety-nine eligible patients participated in the study at 3 different
types of hospitals. After subcutaneous ICG allergy testing, all the patients were
subcutaneously injected with methylene blue and ICG into the subareolar area.
Consequently, 276 SLNs (range 1-7) were identified in 98 subjects (detection
rate: 99%) by using the ICG fluorescence imaging method. In contrast, the blue
dye method only identified 202 SLNs (range 1-7) in 91 subjects (detection rate:
91.92%). Besides, the results of the fluorescence imaging method were similar in
the 3 hospitals. Our findings indicate the universal feasibility of the ICG
fluorescence imaging method for SLNB using the fluorescence image-guided
resection equipment in early breast cancer detection.
PMID- 27497182
TI - Suppression of human alloreactive T cells by linear tetrapyrroles; relevance for
transplantation.
AB - The main limitation to successful transplantation is the antigraft response
developed by the recipient immune system, and the adverse side effects of
immunosuppressive agents which are associated with significant toxicity and
counter indications such as infection and cancer. Furthermore, immunosuppressants
do little to prevent ischemia-reperfusion injury during the transplantation
procedure itself hence there is a growing need to develop novel immunosuppressive
drugs specifically aimed at prolonging graft survival. Linear tetrapyrroles
derived from the breakdown of mammalian heme have been shown in numerous studies
to play a protective role in allograft transplantation and ischemia-reperfusion
injury; however, commercial sources of these products have not been approved for
use in humans. Plants and algae produce equivalent linear tetrapyrroles called
bilins that serve as chromophores in light-sensing. One such marine-derived
tetrapyrrole, phycocyanobilin (PCB), shows significant structural similarity to
mammalian biliverdin (BV) and may prove to be a safer alternative for use in the
clinic if it can exert direct effects on human immune cells. Using a mixed
lymphocyte reaction, we quantified the allogeneic responses of recipient cells to
donor cells and found that PCB, like BV, effectively suppressed proliferation and
proinflammatory cytokine production. In addition, we found that BV and PCB can
directly downregulate the proinflammatory responses of both innate dendritic
cells and adaptive T cells. We therefore propose that PCB may be an effective
therapeutic drug in the clinical setting of transplantation and may also have
wider applications in regulating inappropriate inflammation.
PMID- 27497183
TI - Detection of Felis catus gammaherpesvirus 1 (FcaGHV1) in peripheral blood B- and
T-lymphocytes in asymptomatic, naturally-infected domestic cats.
AB - The domestic cat is natural host to both feline immunodeficiency virus and Felis
catus gammaherpesvirus 1 (FcaGHV1). Comparative data suggest that these agents
might act as synergistic copathogens in feline AIDS-related lymphoma. To identify
leucocyte subsets harbouring gammaherpesvirus DNA, whole blood from 5 healthy,
FcaGHV1-infected cats was labelled with monoclonal antibodies to feline CD21,
CD4, CD8 and CD14 for 4-way fluorescence-activated cell sorting. FcaGHV1gB qPCR
was performed on DNA extracted from purified fractions and whole blood
longitudinally. FcaGHV1 DNA was detected in CD21+, CD4+, CD8+, but not CD14+
cells. Variation in whole blood load, up to 19,788 copies/10(6)cells, was
detected in individual cats over time. FcaGHV1 DNA was undetectable in one cat on
one occasion highlighting that qPCR of whole blood from a single time point will
not detect all cases of FcaGHV1 infection. Further investigation of the role of
FcaGHV1 in feline lymphoid malignancies is warranted.
PMID- 27497184
TI - African horse sickness virus infects BSR cells through macropinocytosis.
AB - Cellular pathways involved in cell entry by African horse sickness virus (AHSV),
a member of the Orbivirus genus within the Reoviridae family, have not yet been
determined. Here, we show that acidic pH is required for productive infection of
BSR cells by AHSV-4, suggesting that the virus is likely internalized by an
endocytic pathway. We subsequently analyzed the major endocytic routes using
specific inhibitors and determined the consequences for AHSV-4 entry into BSR
cells. The results indicated that virus entry is dynamin dependent, but clathrin-
and lipid raft/caveolae-mediated endocytic pathways were not used by AHSV-4 to
enter and infect BSR cells. Instead, binding of AHSV-4 to BSR cells stimulated
uptake of a macropinocytosis-specific cargo and inhibition of Na(+)/H(+)
exchangers, actin polymerization and cellular GTPases and kinases involved in
macropinocytosis significantly inhibited AHSV-4 infection. Altogether, the data
suggest that AHSV-4 infects BSR cells by utilizing macropinocytosis as the
primary entry pathway.
PMID- 27497186
TI - HC-Pro viral suppressor from tobacco vein banding mosaic virus interferes with
DNA methylation and activates the salicylic acid pathway.
AB - Salicylic acid (SA) is an important signalling molecule that is synthesized by
plants and induces the expression of resistance genes. The SA pathway is
typically activated by DNA viruses as well as RNA viruses. Here, we demonstrated
that heper-component protease (HC-Pro) encoded by tobacco vein banding mosaic
virus (TVBMV) decreases in DNA methylation at the promoters of the regulators
ACD6 and NPR1 in the SA pathway. We found that the overexpression of HC-Pro
increases the expression of components in the SA pathway in plants. The results
revealed that HC-Pro interferes in DNA methylation and activates the SA pathway
in the HC-Pro transgenic plants and TVBMV-infected plants. We further found that
the accumulation of siRNAs derived from the promoter repeats of ACD6 and NPR1 is
greatly reduced in the HC-Pro plants. Our results suggested that HC-Pro-mediated
interference with DNA methylation is likely caused by a reduction in accumulation
of siRNAs.
PMID- 27497185
TI - The HCMV US28 vGPCR induces potent Galphaq/PLC-beta signaling in monocytes
leading to increased adhesion to endothelial cells.
AB - US28 transcripts have been detected in primary monocytes and in THP-1 monocytes
infected with HCMV but US28 protein expression has not yet been demonstrated in
these cell types. Moreover, the mechanism(s) by which US28 signals and
contributes to viral pathogenesis in monocytes remains unclear. Here, we show
that US28 protein is robustly expressed in HCMV infected THP-1 monocytes and that
US28 can trigger Galphaq dependent signaling in THP-1 cells infected with HCMV
and in THP-1 cells stably expressing US28. US28 signaling in these cells is
dependent on G-protein coupling, but independent of chemokine binding.
Importantly, we demonstrate that this US28 signaling is functionally important as
it stimulates the adhesion of monocytes to an endothelial monolayer. Our studies,
which demonstrate that US28-driven Galphaq signaling has profound effects on
monocyte biology, suggest that US28 driven phenotypic changes in HCMV infected
monocytes may play important roles in HCMV dissemination and/or pathogenesis.
PMID- 27497187
TI - Identification of adult knee primary bone tumour symptom presentation: A
qualitative study.
AB - OBJECTIVES: The aim of this study was to identify the symptom presentation of
adult knee primary bone tumours from onset to Consultant diagnosis, from combined
patient and healthcare professional perspectives. MATERIALS AND METHODS: A
qualitative study using in-depth semi-structured interviews recruited a purposive
sample of adult patients with a knee primary bone tumour (n = 8) and healthcare
professionals with expertise in orthopaedic oncology (n = 6). Following informed
consent, recorded interviews explored participants' experiences of symptom
presentation. A grounded theory approach was utilised to analyse transcribed
data, producing themes. Methods to increase rigour and trustworthiness were
employed. Recruitment continued until data saturation was achieved. RESULTS: Four
key themes were established: 1] Symptoms started with intermittent pain which
became more severe and more constant, 2] Pain was mechanical in nature but became
more difficult to ease; 3] The pain story was unusual with a protracted symptom
duration and failure to improve with conservative treatment; 4] Non-painful
symptoms included swelling, and systemic signs were uncommon. More similarities
between healthcare professionals' and patients' perceptions were found at
Consultant diagnosis compared to onset. CONCLUSION: New insights of symptom
presentation, particularly in the early stages have been provided which are not
reflected in current guidelines. Although starting similarly to routine
musculoskeletal presentations, a number of distinctive features may enable
earlier diagnosis.
PMID- 27497188
TI - Effects of dry needling to the symptomatic versus control shoulder in patients
with unilateral subacromial pain syndrome.
AB - BACKGROUND: Initial reports suggest that treating myofascial trigger points in
the infraspinatus with dry needling may be effective in treating patients with
shoulder pain. However, to date, high quality clinical trials and thorough
knowledge of the physiologic mechanisms involved is lacking. OBJECTIVES: To
examine the effect of dry needling to the infraspinatus muscle on muscle
function, nociceptive sensitivity, and shoulder range of motion (ROM) in the
symptomatic and asymptomatic shoulders of individuals with unilateral subacromial
pain syndrome. DESIGN: Within-subjects controlled trial. METHODS: Fifty-seven
volunteers with unilateral subacromial pain syndrome underwent one session of dry
needling to bilateral infraspinatus muscles. Outcome assessments, including
ultrasonic measures of infraspinatus muscle thickness, pressure algometry,
shoulder internal rotation and horizontal adduction ROM, and questionnaires
regarding pain and related disability were taken at baseline, immediately after
dry needling, and 3-4 days later. RESULTS: Participants experienced statistically
significant and clinically relevant changes in all self-report measures. Pressure
pain threshold and ROM significantly increased 3-4 days, but not immediately
after dry needling only in the symptomatic shoulder [Pressure pain threshold: 5.1
(2.2, 8.0) N/cm2, internal rotation ROM: 9.6 (5.0, 14.1) degrees, horizontal
adduction ROM: 5.9 (2.5, 9.4) degrees]. No significant changes occurred in
resting or contracted infraspinatus muscle thickness in either shoulder.
CONCLUSIONS: This study found changes in shoulder ROM and pain sensitivity, but
not in muscle function, after dry needling to the infraspinatus muscle in
participants with unilateral subacromial pain syndrome. These changes generally
occurred 3-4 days after dry needling and only in the symptomatic shoulders.
PMID- 27497189
TI - Evidences of abundant hemocyanin variants in shrimp Litopenaeus vannamei.
AB - Hemocyanin (HMC) is a multifunctional immune molecule present in mollusks and
arthropods and functions as an important antigen non-specific immune protein. Our
previous evidences demonstrated that Litopenaeus vannamei HMC might display
extensive molecular diversities. In this study, bioinformatics analysis showed
dozens of variant sequences of the HMC subunit with higher molecular weight from
L. vannamei (LvHMC). Three variant fragments, named as LvHMCV1-3, which shared 85
99% nucleotide identity with that of the classical form of LvHMC (AJ250830.1),
were cloned and characterized. Spatial expression profiles showed that LvHMCV1-3
had different tissue-specific distribution, which were affected by stimulation
with six pathogenic bacteria, including Escherichia coli K12, Vibrio
parahaemolyticus, Vibrio alginolyticus, Vibrio fluvialis, Streptococcus pyogenes
and Staphylococcus aureus, with each variant fragment showing a specific stress
pattern to different bacterial pathogens. Full length cDNA of LvHMCV3 was further
cloned and characterized. The deduced amino acid sequence shared 92% identity
with that of LvHMC, possessed a conserved structure characteristic of the HMC
family and could be clustered into one branch along with other arthropod HMC in a
phylogenetic tree. In addition, the recombinant protein of LvHMCV3 (rLvHMCV3)
showed obvious agglutination activities against three aquaculture pathogenic
bacteria including E. coli K12, V. parahaemolyticus and S.aureus at
concentrations ranging from 31.25-62.5g/mL. It also showed obvious antibacterial
activity against V. parahaemolyticus at concentrations 0.02-0.5mg/mL, and
possessed the best inhibitive effects compared with those of rLvHMCV4 and rLvHMC.
Co-injection of V. parahaemolyticus and rLvHMCV3 in L. vannamei showed
significant decrease of the mortality rate at 24-72h after injection. Therefore,
these studies suggested that L. vannamei had abundant HMC variants, which
possessed obvious resistance to pathogenic infection and might specifically
target on different pathogens in shrimp.
PMID- 27497190
TI - Exceptionally long CDR3H of bovine scFv antigenized with BoHV-1 B-epitope
generates specific immune response against the targeted epitope.
AB - We discovered that some bovine antibodies are amongst the largest known to exist
due to the presence of an exceptionally long CDR3H (>=49 amino acids) with
multiple cysteines that provide a unique knob and stalk structure to the antigen
binding site. The large CDR3H size, unlike mouse and human, provides a suitable
platform for antigenization with large configurational B-epitopes. Here we report
the identification of a B-epitope on the gC envelope protein of bovine herpes
virus type-1 (BoHV-1) recognized by a bovine IgG1 antibody. The identified 156
amino acid long gC fragment (gC156) was expressed as a recombinant protein.
Subsequently, a functional scFv fragment with a 61 amino-acid long CDR3H
(scFv1H12) was expressed such that gC156 was grafted into the CDR3H, replacing
the "knob" region (gC156scFv1H12 or Ag-scFv). Importantly, the Ag-scFv could be
recognized by a neutralizing antibody fragment (scFv3-18L), which suggests that
the engraftment of gC156 into the CDR3H of 1H12 maintained the native
conformation of the BoHV-1 B-epitope. A 3D model of gC156 was generated using
fold-recognition approaches and this was grafted onto the CDR3H stalk of the 1H12
Fab crystal structure to predict the 3D structure of the Ag-scFv. The grafted
antigen in Ag-scFv is predicted to have a compact conformation with the ability
to protrude into the solvent. Upon immunization of bovine calves, the antigenized
scFv (gC156scFv1H12) induced a higher antibody response as compared to free
recombinant gC156. These observations suggest that antigenization of bovine scFv
with an exceptionally long CDR3H provides a novel approach to developing the next
generation of vaccines against infectious agents that require induction of
protective humoral immunity.
PMID- 27497191
TI - Evaluation of dried blood spot samples for hepatitis C virus detection and
quantification.
AB - BACKGROUND: Dried blood spots (DBS) could be an excellent alternative for HCV
diagnosis, since it is less invasive and can be stored and transported without
refrigeration. OBJECTIVES: The aim of this study was to optimize quantitative and
qualitative methods for HCV detection in DBS. STUDY DESIGN: DBS and serum samples
were collected from 99 subjects (59 anti-HCV/HCV RNA positive and 40 seronegative
samples). Seven extraction methods and different PCR parameters were evaluated in
DBS samples in the quantitative RT-PCR (qRT-PCR) developed to amplify the 5'
noncoding region of HCV. A qualitative PCR for amplification of NS5B region of
HCV was also valued and the nested-PCR sequenced. RESULTS: The qRT-PCR showed
good correlation to commercial assay for HCV viral measurement in serum. To
quantify HCV RNA in DBS, it was necessary to increase reverse transcriptase and
cDNA concentration. HCV RNA quantification in DBS demonstrated sensitivity of
65.9%, 100% of specificity and kappa statistic of 0.65. The median viral load of
DBS samples was 5.38 log10 copies/ml (minimum value=1.76 and maximum value=10.48
log10 copies/ml). HCV RNA was detected in NS5B regions and nucleotide sequences
obtained in 43 serum and 11 DBS samples. The presence of the same subtype was
observed in paired serum and DBS samples. CONCLUSIONS: In this study, it was
possible to demonstrate that, despite the low sensitivity, the optimized protocol
was able to determine the viral load, as well as, the infecting HCV genotype,
validating the usefulness of DBS for viral load determination and molecular
epidemiology studies of HCV.
PMID- 27497192
TI - Task-shifting - A practical strategy to improve the global access to treatment
for chronic hepatitis C.
PMID- 27497193
TI - Circulating midkine in children with Henoch-Schonlein purpura: Clinical
implications.
AB - BACKGROUND: Midkine (MK) is a heparin-binding growth factor, which behaves like a
cytokine, involved in various cellular processes such as cellular proliferation,
differentiation, survival, adhesion, and migration. Studies provided evidence for
a role of MK in acute and chronic inflammatory processes. The association between
midkine and Henoch-Schonlein purpura (HSP) has not yet been explored. The aim of
our study was to investigate the potential role of midkine in children with HSP.
METHODS: A total of 152 cases consisting of 92 children with HSP and 60 age- and
sex-matched healthy control children were enrolled in this prospective study.
Circulating midkine, IL-2, IL-4, IL-6, IL-10, TNF, IFN-gamma, and IL-17A was
measured in all of the 92 patients and 60 healthy controls. Midkine diagnostic
value was evaluated by receiver operating characteristic (ROC) analysis. RESULTS:
Renal involvement occurred in 36 of the 92 patients. Circulating midkine level
was elevated in children with HSPN than those of patients without renal
involvement and of the controls (326.58 (266.58-459.25) pg/ml versus 280.72
(233.67-384.36) pg/ml and 217.3 (198.98-243.65) pg/ml, respectively; P<0.05).
Midkine positively correlated with IL-4, IL-6, IL17A, IgA and IgE. The threshold
MK concentration of HSPN was 295.58pg/ml, with the sensitivity and specificity of
80.6% and 88.3%, respectively. The area under the receiver operating
characteristic (ROC) curve (AUCROC) of MK was 0.902. CONCLUSIONS: MK seems to be
involved in the development of HSP. Measurement of serum levels of MK is helpful
in confirming the diagnosis of HSP and predicting HSPN.
PMID- 27497194
TI - Inhibition of curcumin on myeloid-derived suppressor cells is requisite for
controlling lung cancer.
AB - Lung cancer remains the leading cause of cancer mortality. Myeloid-derived
suppressor cells (MDSCs) are potent immune-suppressive cells and present in most
cancer patients. Recently, several studies have shown that curcumin inhibits the
expansion of MDSCs in some cancers. However, it is not clear how curcumin
modulates the suppressive function of MDSCs, and whether curcumin achieves anti
tumor effects via regulating the expansion of MDSCs in lung cancer. Here, our
results showed that curcumin significantly inhibited tumor growth in a Lewis lung
carcinoma (LLC) isogenic tumor model. Curcumin reduced the accumulation of MDSCs
in spleen and tumor tissue in LLC isogenic model. And curcumin promoted the
maturation and differentiation of MDSCs in tumor tissue. Notably, curcumin
inhibited the expression level of immune suppressive factors of MDSCs, arginase-1
(Arg-1) and ROS, in purified MDSCs from tumor tissue in vivo. Expectedly,
curcumin also inhibited the immunosuppressive function of isolated MDSCs from
tumor tissue and spleen of tumor bearing mice in vitro. Moreover, curcumin
decreased the level of IL-6 in the tumor tissue and serum from LLC-bearing mice.
Taken together, curcumin indeed possesses anti-cancer effect and inhibits the
accumulation and function of MDSCs. And curcumin reduces the level of IL-6 in
tumor-bearing mice to impair the expansion and function of MDSCs. These results
suggest that inhibition of MDSCs in tumor is requisite for controlling lung
cancer.
PMID- 27497195
TI - Trifunctional molecular beacon-mediated quadratic amplification for highly
sensitive and rapid detection of mercury(II) ion with tunable dynamic range.
AB - Analyses of target with low abundance or concentration varying over many orders
of magnitude are severe challenges faced by numerous assay methods due to their
modest sensitivity and limited dynamic range. Here, we introduce a homogeneous
and rapid quadratic polynomial amplification strategy through rational design of
a trifunctional molecular beacon, which serves as not only a reporter molecule
but also a bridge to couple two stage amplification modules without adding any
reaction components or process other than basic linear amplification. As a test
bed for our studies, we took mercury(II) ion as an example and obtained a high
sensitivity with detection limit down to 200 pM within 30min. In order to create
a tunable dynamic range, homotropic allostery is employed to modulate the target
specific binding. When the number of metal binding site varies from 1 to 3,
signal response is programmed accordingly with useful dynamic range spanning 50,
25 and 10 folds, respectively. Furthermore, the applicability of the proposed
method in river water and biological samples are successfully verified with good
recovery and reproducibility, indicating considerable potential for its
practicality in complex real samples.
PMID- 27497196
TI - Highly sensitive electrochemiluminescent immunosensor based on gold nanoparticles
functionalized zinc oxide nanorod and poly(amidoamine)-graphene for detecting
brombuterol.
AB - beta-adrenergic agonists (beta-agonists) recognized as a growth promoter will
reflect the health of human. Sensitive detection of beta-agonists in foodstuff is
valuable for the health of animals and human. A novel ultrasensitive competition
type electrochemiluminescent (ECL) immunosensor was developed for detecting
brombuterol (Brom) based on CdTe Quantum dot (QDs) and polyamidoamine dendrimer
(PAMAM, G2) modified graphene oxide (GO) (CdTe QDs-PAMAM-GO composite) as
bioprobe for the first time. The surface of glassy carbon electrode (GCE) was
coated with AuNPs-ZnO NRs composite film as the platform, which facilitated the
electronic transmission rate to enhance the ECL intensity and provide enough
active sites for capturing antibody. The resulting ECL immunosensor enabled the
real samples detection of Brom with a lower detection limit of 0.3pgmL(-1)
(S/N=3) and a wider linear range from 0.001 to 500ngmL(-1). The proposed
immunosensor coupled with the excellent advantages of CdTe QDs-PAMAM-GO and AuNPs
ZnO NRs composite displayed high sensitivity and long-term stability, and
provided an approach for determining other important biomarkers.
PMID- 27497197
TI - Electrochemical DNA probe for Hg(2+) detection based on a triple-helix DNA and
Multistage Signal Amplification Strategy.
AB - In this work, an ultrasensitive electrochemical sensor was developed for
detection of Hg(2+). Gold nanoparticles decorated bovine serum albumin reduction
of graphene oxide (AuNP-BSA-rGO) were used as subsurface material for the
immobilization of triple-helix DNA. The triple-helix DNA containing a thiol
labelled single-stranded DNA (sDNA) and a thymine-rich DNA (T-rich DNA), which
could be unwinded in the present of Hg(2+) to form more stable thymine-Hg(2+)
thymine (T-Hg(2+)-T) complex. T-Hg(2+)-T complex was then removed and the sDNA
was left on the electrode. At this time, gold nanoparticle carrying thiol
labelled cytosine-rich complementary DNA (cDNA-AuNP) could bind with the free
sDNA. Meanwhile, the other free cDNA on AuNP could bind with each other in the
present of Ag(+) to form the stable cytosine-Ag(+)-cytosine (C-Ag(+)-C) complex
and circle amplification. Plenty of C-Ag(+)-C could form silver nanoclusters by
electrochemical reduction and the striping signal of Ag could be measured for
purpose of the final electrochemical detection of Hg(2+). This sensor could
detect Hg(2+) over a wide concentration range from 0.1 to 130nM with a detection
limit of 0.03nM.
PMID- 27497198
TI - Fluorescent molecularly imprinted nanogels for the detection of anticancer drugs
in human plasma.
AB - Several fluorescent molecularly imprinted nanogels for the detection of the
anticancer drug sunitinib were synthesized and characterized. A selection of
functional monomers based on different aminoacids and coumarin allowed isolation
of polymers with very good rebinding properties and sensitivities. The direct
detection of sunitinib in human plasma was successfully demonstrated by
fluorescence quenching of the coumarin-based nanogels. The plasma sample simply
diluted in DMSO allowed the recovery of various amounts of sunitib, as determined
by an averaged calibration curve. The LOD was 400nM, with within-run variability
<9%, day to day variability <5%, and good accuracy in the recovery of sunitinib
from spiked samples.
PMID- 27497199
TI - Dual-responsive immunosensor that combines colorimetric recognition and
electrochemical response for ultrasensitive detection of cancer biomarkers.
AB - We developed a nanoroughened, biotin-doped polypyrrole immunosensor for the
detection of tumor markers through dual-signal (electrochemical and colorimetric)
channels, electrochemical and colorimetric, that demonstrates remarkable
analytical performance. A rapid, one-step electric field-mediated method was
employed to fabricate the immunosensor with nanoscale roughness by simply
modulating the applied electrical potential. We demonstrated the successful
detection of three tumor markers (CA125, CEA, and PSA) via the double enzymatic
signal amplifications in the presence of a target antigen, ultimately leading to
desired diagnostic accuracy and reliability. The addition of multiple horseradish
peroxidase (HRP)- and antibody-labeled nanoparticles greatly amplified the signal
and simplified the measurement of cancer biomarker proteins by sequentially
magnifying electrochemical and colorimetric signals in a single platform. The two
parallel assays performed using the proposed immunosensor have yielded highly
consistent and reproducible results. Additionally, for the analysis of plasma
samples in a clinical setting, the values obtained with our immunosensor were
validated by correlating the results with those of a standard radioimmunoassay
(RIA), which obtained very similar clinically valid responses.
PMID- 27497200
TI - Experimental, computational and chemometrics studies of BSA-vitamin B6
interaction by UV-Vis, FT-IR, fluorescence spectroscopy, molecular dynamics
simulation and hard-soft modeling methods.
AB - The interaction of pyridoxine (Vitamin B6) with bovine serum albumin (BSA) is
investigated under pseudo-physiological conditions by UV-Vis, fluorescence and
FTIR spectroscopy. The intrinsic fluorescence of BSA was quenched by VB6, which
was rationalized in terms of the static quenching mechanism. According to
fluorescence quenching calculations, the bimolecular quenching constant (kq),
dynamic quenching (KSV) and static quenching (KLB) at 310K were obtained. The
efficiency of energy transfer and the distance between the donor (BSA) and the
acceptor (VB6) were calculated by Foster's non-radiative energy transfer theory
and were equal to 41.1% and 2.11nm. The collected UV-Vis and fluorescence spectra
were combined into a row-and column-wise augmented matrix and resolved by
multivariate curve resolution-alternating least squares (MCR-ALS). MCR-ALS helped
to estimate the stoichiometry of interactions, concentration profiles and pure
spectra for three species (BSA, VB6 and VB6-BSA complex) existed in the
interaction procedure. Based on the MCR-ALS results, using mass balance
equations, a model was developed and binding constant of complex was calculated
using non-linear least squares curve fitting. FT-IR spectra showed that the
conformation of proteins was altered in presence of VB6. Finally, the combined
docking and molecular dynamics (MD) simulations were used to estimate the binding
affinity of VB6 to BSA. Five-nanosecond MD simulations were performed on bovine
serum albumin (BSA) to study the conformational features of its ligand binding
site. From MD results, eleven BSA snapshots were extracted, at every 0.5ns, to
explore the binding affinity (GOLD score) of VB6 using a docking procedure. MD
simulations indicated that there is a considerable flexibility in the structure
of protein that affected ligand recognition. Structural analyses and docking
simulations indicated that VB6 binds to site I and GOLD score values depend on
the conformations of both BSA and ligand. Molecular modeling results showed that
VB6-BSA complex formed not only on the basis of electrostatic forces, but also on
the basis of pi-pi staking and hydrogen bond. There was an excellent agreement
between the experimental and computational results. The results presented in this
paper, will offer a reference for detailed and systematic studies on the
biological effects and action mechanism of small molecules with proteins.
PMID- 27497201
TI - Anatomy and Disorders of the Oral Cavity of Ornamental Fish.
AB - Ornamental fish represent the largest and most diverse group of exotic animals
kept as pets. The specific oral anatomy of each family or selected species has
evolved to suit the natural environment, feeding behaviors, food or prey type,
and location of the food/prey in the water column. The anatomy can change over
the life of the animal, from fry to adult. The oral cavity of fish is susceptible
to many problems including infectious and parasitic diseases, trauma, and
neoplasia. Diagnosis may involve wet mount preparations of exfoliative cytology
from the lesion, histopathology, and bacterial or fungal culture.
PMID- 27497202
TI - Anatomy and Disorders of the Oral Cavity of Reptiles and Amphibians.
AB - A wide variety of disorders may be seen affecting the reptile and amphibian oral
cavity. Owners can easily miss problems until they are at an advanced stage
because of the difficulty of examining the oral cavity at home. Because many
problems are secondary to an inappropriate environment or diet and may be related
to systemic disease, a full history and clinical examination is always required.
Treatment of oral disorders also requires a holistic approach including
correction of any predisposing factors in order for long-term successful
resolution of the problem.
PMID- 27497203
TI - Anatomy and Disorders of the Beak and Oral Cavity of Birds.
AB - Cranial kinesis of the avian beak is complex; particularly in birds with
prokinetic beak movement, such as psittacine birds. A number of diseases can
result in damage to the bony and soft tissue structures of the beak and can lead
to secondary pathology, such as beak deviation, abnormal rhamphothecal growth and
wear, and opportunistic infections. A solid understanding of species-specific
anatomic variations is essential before attempting rhamphothecal restoration or
surgical repair. Many diseases of the oral cavity can appear similar on initial
clinical evaluation and therefore warrant appropriate diagnostic testing.
PMID- 27497204
TI - Anatomy, Physiology and Non-dental Disorders of the Mouth of Pet Rabbits.
AB - The first part of this review focuses on the anatomy and physiology of the rabbit
mouth. Practical understanding is critical to comprehend the dynamic pathologic
changes of dental disease, which is one of the most common presenting problems in
rabbits. The major theories of the etiopathogenesis of dental disease are
presented. The second part focuses on non-dental oral disorders, which encompass
only a small incidence of stomatognathic diseases when compared with dental
disease. These diseases are primarily composed of infections (treponematosis,
oral papillomatosis), neoplasia (frequently involving calcified tissue
proliferation), and congenital abnormalities (mandibular prognathism, absent peg
teeth, supernumerary peg teeth).
PMID- 27497205
TI - Diagnostic Imaging of Dental Disease in Pet Rabbits and Rodents.
AB - Diagnostic imaging techniques are of paramount importance for dentistry and oral
disorders of rabbits, rodents, and other exotic companion mammals. Aside from
standard radiography, stomatoscopy is a complementary tool allowing a thorough
and detailed inspection of the oral cavity. Computed tomography (CT) generates
multiple 2-dimensional views and 3-dimensional reconstructions providing superior
diagnostic accuracy also useful for prognosis and treatment of advanced dental
disease and its related complications. MRI is a diagnostic imaging technique
additional to CT used primarily to enhance soft tissues, including complex
odontogenic abscesses.
PMID- 27497206
TI - Intraoral Treatment of Dental Disease in Pet Rabbits.
AB - The intraoral treatment of dental disease in pet rabbits follows a complete
clinical examination, intraoral inspection under general anesthesia, and
diagnostic imaging. It also implies thorough knowledge of dental disease in this
species. The most common intraoral procedures are extraction of incisor teeth,
coronal reduction, and extraction of cheek teeth. These dental procedures require
specific instruments and equipment. They should be performed in conjunction with
supportive and medical treatment followed by appropriate nutrition.
PMID- 27497207
TI - Surgical Treatment of Facial Abscesses and Facial Surgery in Pet Rabbits.
AB - Odontogenic facial abscesses associated with periapical infections and
osteomyelitis of the jaw represent an important part of the acquired and
progressive dental disease syndrome in pet rabbits. Complications such as
retromasseteric and retrobulbar abscesses, extensive osteomyelitis of the
mandible, and empyemas of the skull are possible sequelae. Standard and advanced
diagnostic imaging should be pursued to make a detailed and proper diagnosis, and
plan the most effective surgical treatment. This article reviews the surgical
anatomy, the pathophysiology, and the classification of abscesses and empyemas of
the mandible, the maxilla, and the skull. It also discusses surgical techniques
for facial abscesses.
PMID- 27497208
TI - Anatomy and Disorders of the Oral Cavity of Guinea Pigs.
AB - Acquired dental disease represents the most common oral disorder of guinea pigs.
Most patients are presented with nonspecific clinical signs and symptoms, such as
weight loss, reduced food intake, difficulty chewing and/or swallowing. The
physical examination must be followed by standard radiography and/or computed
tomography, and thorough inspection under general anesthesia. Several
complications may follow, including periodontal disease, subluxation of the
temporomandibular joint, periapical infection, and abscessation. The dental
treatment is aimed to restore the proper length and shape of both the incisor and
cheek teeth, associated with medical and supportive treatment. Abscesses should
be surgically addressed by complete excision.
PMID- 27497209
TI - Anatomy and Disorders of the Oral Cavity of Chinchillas and Degus.
AB - Dental disease is among the most common causes for chinchillas and degus to
present to veterinarians. Most animals with dental disease present with weight
loss, reduced food intake/anorexia, and drooling. Degus commonly present with
dyspnea. Dental disease has been primarily referred to as elongation and
malocclusion of the cheek teeth. Periodontal disease, caries, and tooth
resorption are common diseases in chinchillas, but are missed frequently during
routine intraoral examination, even performed under general anesthesia. A
diagnostic evaluation, including endoscopy-guided intraoral examination and
diagnostic imaging of the skull, is necessary to detect oral disorders and to
perform the appropriate therapy.
PMID- 27497210
TI - Anatomy and Disorders of the Oral Cavity of Rat-like and Squirrel-like Rodents.
AB - The order Rodentia comprises more than 2000 species divided into 3 groups based
on anatomic and functional differences of the masseter muscle. Myomorph and
sciuromorph species have elodont incisors and anelodont cheek teeth, unlike
hystrichomorph species which have full anelodont dentition. Diseases of incisors
and cheek teeth of rat-like and squirrel-like rodents result in a wide variety of
symptoms and clinical signs. Appropriate diagnostic testing and imaging
techniques are required to obtain a definitive diagnosis, formulate a prognosis,
and develop a treatment plan. A thorough review of elodontoma, odontoma, and
pseudo-odontoma is provided, including treatment of pseudo-odontomas in prairie
dogs.
PMID- 27497211
TI - Anatomy and Disorders of the Oral Cavity of Ferrets and Other Exotic Companion
Carnivores.
AB - Exotic companion carnivores such as ferrets, skunks, fennec foxes, coatimundis,
raccoons, and kinkajous presented in clinical practice share similar dental
anatomy, function, and diseases. The domestic ferret serves as the representative
species for this group with its anatomy, diseases, and conditions described in
detail. Dog and cat guidelines for veterinary and home care seem to be relevant
and applicable, including dental endodontic procedures. Annual or biannual dental
examinations and prophylaxis are recommended. The most common dental and oral
problems are tooth wear, plaque and calculus, teeth fractures, gingivitis and
periodontitis, tooth loss, abscesses, oral ulceration, tonsillitis, and
neoplasia.
PMID- 27497212
TI - Anatomy and Disorders of the Oral Cavity of Miscellaneous Exotic Companion
Mammals.
AB - Unusual mammalian species such as the hedgehog, sugar glider, and miniature pig
are encountered with increasing frequency in exotic companion medicine. Disease
of the oral cavity can occur in any species; although occasionally encountered in
exotic mammalian species, it is rarely described in the literature. Anatomy and
dentition vary significantly; diagnosis and treatment are often extrapolated from
that known in other species. The best-documented disease of the oral cavity in
this group of species is oral neoplasia in the hedgehog.
PMID- 27497213
TI - New Perspectives on Dentistry and Oral Disorders of Exotic Companion Animals.
PMID- 27497214
TI - Prognostic value of imbalanced interhemispheric functional coordination in early
therapeutic efficacy in major depressive disorder.
AB - This study aims to explore the early response of antidepressant therapy by
measuring the voxel-mirrored homotopic connectivity (VMHC) in major depressive
disorder (MDD). Eighty-two MDD patients [n=42 treatment-responsive depression
(RD) and n=40 non-responding depression (NRD)] and n=50 normal controls (NC)
underwent clinical measures and a magnetic resonance imaging scan, and the VMHC
values were calculated. Receiver operating characteristic (ROC) curve analysis
was applied to determine the capability of altered VMHC to distinguish NRD. The
NRD showed significantly decreased VMHC in bilateral precuneus (PCU) and inferior
temporal gyrus (ITG), and increased VMHC in middle frontal gyrus (MFG) and
caudate nucleus as compared to RD. When compared with NC, the NRD exhibited
reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral
gyrus. Moreover, VHMC in medial frontal gyrus, postcentral gyrus and precentral
gyrus were significantly decreased in RD. Correlation analysis showed that
reduced VMHC in PCU was negatively correlated with the baseline HAMD score of the
NRD group. The ROC curve indicated that the combined changes of the three
regional VMHC (PCU, ITG and MFG) could effectively identify NRD. The current
study suggests that interhemispheric asynchrony may represents a novel neural
trait underlying the prediction of early therapeutic outcome in MDD.
PMID- 27497215
TI - Abnormal interhemispheric resting state functional connectivity of the insula in
heroin users under methadone maintenance treatment.
AB - Abnormal interhemispheric functional connectivity is attracting more and more
attention in the field of substance use. This study aimed to examine 1) the
differences in interhemispheric functional connections of the insula with the
contralateral insula and other brain regions between heroin users under methadone
maintenance treatment (MMT) and healthy controls, and 2) the association between
heroin users' interhemispheric insular functional connectivity using resting
functional magnetic resonance imaging (fMRI) and the results of urine heroin
analysis. Sixty male right-handed persons, including 30 with heroin dependence
under MMT and 30 healthy controls, were recruited to this study. Resting fMRI
experiments and urine heroin analysis were performed. Compared with the controls,
the heroin users had a significantly lower interhemispheric insular functional
connectivity. They also exhibited lower functional connectivity between insula
and contralateral inferior orbital frontal lobe. After controlling for age,
educational level and methadone dosage, less deviation of the interhemispheric
insula functional connectivity was significantly associated with a lower risk of
a positive urine heroin analysis result. Our findings demonstrated that the
heroin users under MMT had abnormal long-range and interhemispheric resting
functional connections. Those with a less dysfunctional interhemispheric insula
functional connectivity had a lower risk of a positive urine heroin test.
PMID- 27497217
TI - Hidden Depths in the Hippocampal Circuitry.
AB - Danielson et al. (2016) use calcium imaging in mice performing a treadmill task
to reveal differences in space-coding dynamics between deep and superficial
sublayers of hippocampal CA1, suggesting how the hippocampus might encode both
stable and dynamic information simultaneously.
PMID- 27497216
TI - Regulation of Plexin: A Ring of Structural Twists and Turns.
AB - The regulation of the guidance receptor plexin is incompletely understood. In
this issue, Kong et al. (2016) present crystal structures of the full-length
extracellular region of class A plexins, revealing its dual role in both
autoinhibition and activation.
PMID- 27497218
TI - Disrupting the Grid Cells' Need for Speed.
AB - Hinman et al. demonstrate the presence of two speed signals in the rodent medial
entorhinal cortex that are differentially affected by muscimol inactivation of
medial septum. The results reveal important constraints on several computational
models of grid cell firing.
PMID- 27497219
TI - A Nimble Working Memory.
AB - In this issue of Neuron, Sprague et al. (2016) report fMRI evidence that a
degraded working memory representation can be restored by a later cue. The
findings raise new questions about the neural mechanisms that underlie such
dynamic representational shifts.
PMID- 27497220
TI - Clinical Concepts Emerging from fMRI Functional Connectomics.
AB - Recent advances in connectomics have led to a synthesis of perspectives regarding
the brain's functional organization that reconciles classical concepts of
localized specialization with an appreciation for properties that emerge from
interactions across distributed functional networks. This provides a more
comprehensive framework for understanding neural mechanisms of normal cognition
and disease. Although fMRI has not become a routine clinical tool, research has
already had important influences on clinical concepts guiding diagnosis and
patient management. Here we review illustrative examples. Studies demonstrating
the network plasticity possible in adults and the global consequences of even
focal brain injuries or disease both have had substantial impact on modern
concepts of disease evolution and expression. Applications of functional
connectomics in studies of clinical populations are challenging traditional
disease classifications and helping to clarify biological relationships between
clinical syndromes (and thus also ways of extending indications for, or "re
purposing," current treatments). Large datasets from prospective, longitudinal
studies promise to enable the discovery and validation of functional connectomic
biomarkers with the potential to identify people at high risk of disease before
clinical onset, at a time when treatments may be most effective. Studies of pain
and consciousness have catalyzed reconsiderations of approaches to clinical
management, but also have stimulated debate about the clinical meaningfulness of
differences in internal perceptual or cognitive states inferred from functional
connectomics or other physiological correlates. By way of a closing summary, we
offer a personal view of immediate challenges and potential opportunities for
clinically relevant applications of fMRI-based functional connectomics.
PMID- 27497221
TI - Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust.
AB - The emerging field of bioelectronic medicine seeks methods for deciphering and
modulating electrophysiological activity in the body to attain therapeutic
effects at target organs. Current approaches to interfacing with peripheral
nerves and muscles rely heavily on wires, creating problems for chronic use,
while emerging wireless approaches lack the size scalability necessary to
interrogate small-diameter nerves. Furthermore, conventional electrode-based
technologies lack the capability to record from nerves with high spatial
resolution or to record independently from many discrete sites within a nerve
bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic
backscatter system for powering and communicating with implanted bioelectronics.
We show that ultrasound is effective at delivering power to mm-scale devices in
tissue; likewise, passive, battery-less communication using backscatter enables
high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG)
signals from anesthetized rats. These results highlight the potential for an
ultrasound-based neural interface system for advancing future bioelectronics
based therapies.
PMID- 27497222
TI - Defining preBotzinger Complex Rhythm- and Pattern-Generating Neural Microcircuits
In Vivo.
AB - Normal breathing in rodents requires activity of glutamatergic Dbx1-derived
(Dbx1(+)) preBotzinger Complex (preBotC) neurons expressing somatostatin (SST).
We combined in vivo optogenetic and pharmacological perturbations to elucidate
the functional roles of these neurons in breathing. In transgenic adult mice
expressing channelrhodopsin (ChR2) in Dbx1(+) neurons, photoresponsive preBotC
neurons had preinspiratory or inspiratory firing patterns associated with
excitatory effects on burst timing and pattern. In transgenic adult mice
expressing ChR2 in SST(+) neurons, photoresponsive preBotC neurons had
inspiratory or postinspiratory firing patterns associated with excitatory
responses on pattern or inhibitory responses that were largely eliminated by
blocking synaptic inhibition within preBotC or by local viral infection limiting
ChR2 expression to preBotC SST(+) neurons. We conclude that: (1) preinspiratory
preBotC Dbx1(+) neurons are rhythmogenic, (2) inspiratory preBotC Dbx1(+) and
SST(+) neurons primarily act to pattern respiratory motor output, and (3) SST(+)
neuron-mediated pathways and postsynaptic inhibition within preBotC modulate
breathing pattern.
PMID- 27497223
TI - Projection-Specific Dynamic Regulation of Inhibition in Amygdala Micro-Circuits.
AB - Cannabinoid receptor type 1 (CB1R)-expressing CCK interneurons are key regulators
of cortical circuits. Here we report that retrograde endocannabinoid signaling
and CB1R-mediated regulation of inhibitory synaptic transmission onto basal
amygdala principal neurons strongly depend on principal neuron projection target.
Projection-specific asymmetries in the regulation of local inhibitory micro
circuits may contribute to the selective activation of distinct amygdala output
pathways during behavioral changes.
PMID- 27497225
TI - Dopamine Does Double Duty in Motivating Cognitive Effort.
PMID- 27497224
TI - Restoring Latent Visual Working Memory Representations in Human Cortex.
AB - Working memory (WM) enables the storage and manipulation of limited amounts of
information over short periods. Prominent models posit that increasing the number
of remembered items decreases the spiking activity dedicated to each item via
mutual inhibition, which irreparably degrades the fidelity of each item's
representation. We tested these models by determining if degraded memory
representations could be recovered following a post-cue indicating which of
several items in spatial WM would be recalled. Using an fMRI-based image
reconstruction technique, we identified impaired behavioral performance and
degraded mnemonic representations with elevated memory load. However, in several
cortical regions, degraded mnemonic representations recovered substantially
following a post-cue, and this recovery tracked behavioral performance. These
results challenge pure spike-based models of WM and suggest that remembered items
are additionally encoded within latent or hidden neural codes that can help
reinvigorate active WM representations.
PMID- 27497226
TI - Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root
Ganglion Neurons with Proprioceptive Function.
PMID- 27497227
TI - Pilot study on arsenic removal from groundwater using a small-scale reverse
osmosis system-Towards sustainable drinking water production.
AB - Arsenic contamination of groundwater is posing a serious challenge to drinking
water supplies on a global scale. In India and Bangladesh, arsenic has caused the
most serious public health issue in the world for nearly two decades. The aim of
this work was to study an arsenic removal system based on reverse osmosis at
pilot scale treating two different water sources from two different locations in
the State of Bihar, India. For this purpose two villages, Bind Toli and Ramnagar
in the Patna District were selected, both located very close to the river Ganga.
The trials were conducted with aerated and non-aerated groundwater. It is the
first time that the arsenic removal efficiency for aerated and non-aerated
groundwater by reverse osmosis technology in combination with an energy-saving
recovery system have been studied. As the principle of reverse osmosis requires a
relatively high pressure, its energy demand is naturally high. By using an energy
recovery system, this demand can be lowered, leading to an energy demand per
liter permeate of 3-4Wh/L only. Due to high iron levels in the groundwater and as
a consequence the precipitation of ferric (hydr)oxides, it was necessary to
develop a granular media filter for the trials under aeration in order to protect
the membrane from clogging. Two different materials, first locally available
sand, and second commercially available anthracite were tested in the granular
media filter. For the trials with aerated groundwater, total arsenic removal
efficiency at both locations was around 99% and the arsenic concentration in
permeate was in compliance with the WHO and National Indian Standard of 10MUg/L.
However, trials under anoxic conditions with non-aerated groundwater could not
comply with this standard. Additionally a possible safe discharge of the reverse
osmosis concentrate into an abandoned well was studied. It was observed that re
injection of reject water underground may offer a safe disposal option. However,
long-term hydrogeological studies need to be conducted for confirmation.
PMID- 27497228
TI - Comparative performance evaluation of multi-metal resistant fungal strains for
simultaneous removal of multiple hazardous metals.
AB - In the present study, five fungal strains viz., Aspergillus terreus AML02,
Paecilomyces fumosoroseus 4099, Beauveria bassiana 4580, Aspergillus terreus PD
17, Aspergillus fumigatus PD-18, were screened for simultaneous multimetal
removal. Highest metal tolerance index for each individual metal viz., Cd, Cr,
Cu, Ni, Pb and Zn (500mg/L) was recorded for A. fumigatus for the metals (Cd,
0.72; Cu, 0.72; Pb, 1.02; Zn, 0.94) followed by B. bassiana for the metals (Cd,
0.56; Cu, 0.14; Ni, 0.29; Zn, 0.85). Next, the strains were exposed to multiple
metal mixture (Cd, Cr, Cu, Ni, Pb and Zn) of various concentrations (6, 12, 18,
30mg/L). Compared to other strains, B. bassiana and A. fumigatus had higher cube
root growth (k) constants indicating their better adaptability to multi metal
stress. After 72h, multimetal accumulation potential of B. bassiana (26.94+/
0.07mg/L) and A. fumigatus (27.59+/-0.09mg/L) were higher than the other strains
at initial multimetal concentration of 30mg/L. However, considering the post
treatment concentrations of individual metals in multimetal mixture (at all the
tested concentrations), A. fumigatus demonstrated exceptional performance and
could bring down the concentrations of Cd, Cu, Ni, Pb and Zn below the threshold
level for irrigation prescribed by Food and Agriculture Organization (FAO).
PMID- 27497230
TI - Structural regulation of self-assembled iron oxide/polymer microbubbles towards
performance-tunable magnetic resonance/ultrasonic dual imaging agents.
AB - Fe3O4/polymer hybrid microcapsules were prepared via a template-free route which
is based on polyamine-salt aggregates (PSAs) self-assembly approach. The
measurements of transmission electron microscopy (TEM) indicated that the
diameter and shell thickness of the microcapsules could be tuned by varying the
experimental conditions, such as the concentration of reactants and evolution
time employed during the PSA assembly. The results of vibrating sample
magnetometer (VSM) demonstrated that the magnetic nanoparticles content of the
synthesized microcapsules was tunable and all samples exhibited superparamagnetic
behavior. After filling appropriate perfluorocarbon into the inner cavities of
the microcapsules, the biomedical applications of the resultant microbubbles,
including ultrasonic imaging (USI) and magnetic resonance imaging (MRI), were
studied in vitro. It showed that the synthesized magnetic microbubbles possessed
both strong ultrasound contrast enhancement capability and high relaxation rate.
The excellent acoustic and magnetic properties of these self-assembled
microbubbles ensure that the Fe3O4/polymer hybrid microbubbles have great
potential as MRI/USI dual-modality contrast agents.
PMID- 27497229
TI - Amelioration of premature aging in mtDNA mutator mouse by exercise: the interplay
of oxidative stress, PGC-1alpha, p53, and DNA damage. A hypothesis.
AB - The mtDNA mutator mouse lacks the proofreading capacity of the sole mtDNA
polymerase, leading to accumulation of somatic mtDNA mutations, and a profound
premature aging phenotype including elevated oxidative stress and apoptosis, and
reduced mitochondrial function. We have previously reported that endurance
exercise alleviates the aging phenotype in the mutator mice, reduces oxidative
stress, and enhances mitochondrial biogenesis. Here we summarize our findings,
with the emphasis on the central role of p53 in these adaptations. We demonstrate
that mtDNA in sedentary and exercised PolG mice carry similar amounts of
mutations in muscle, but in addition to that sedentary mice have more non
mutational damage, which is mitigated by exercise. It follows therefore that the
profound alleviation of the mtDNA mutator phenotype in muscle by exercise may not
require a reduction in mtDNA mutational load, but rather a decrease of mtDNA
damage and/or oxidative stress. We further hypothesize that the observed
'alleviation without a reduction of mutational load' implies that the oxidative
stress in PolG muscle is maintained, at least in part, by the 'malicious cycle',
a hypothetical positive feedback potentially driven by the 'transcriptional
mutagenesis', that is the conversion of chemically modified nucleotides into
mutant RNA bases by the mitochondrial RNA polymerase.
PMID- 27497231
TI - Gold nanoparticles-decorated silver-bipyridine nanobelts for the construction of
mediatorless hydrogen peroxide biosensor.
AB - Au nanoparticles modified with 4-mercaptopyridine and 6-mercapto-1-hexanol were
used as coordination agents to prepare a novel hybrid nanomaterial with Ag:4,4'
bipyridine nanobelts. This nanohybrid was employed to modify glassy carbon
electrodes and to construct a horseradish peroxidase-based mediatorless
amperometric biosensor for H2O2. The electrode, poised at -100mV, exhibited a
rapid response within 4s and a linear calibration range from 90pM to 6.5nM H2O2.
The biosensor showed a high sensitivity of 283A/Mcm(2) and a very low detection
limit of 45pM at a signal-to-noise ratio of 3. The enzyme biosensor showed high
stability when stored at 4 degrees C under dry conditions, retaining over 96% and
78% of its initial activity after 15 and 30days of storage at 4 degrees C,
respectively.
PMID- 27497232
TI - Nanocrystallinity effects on osteoblast and osteoclast response to silicon
substituted hydroxyapatite.
AB - HYPOTHESIS: Silicon substituted hydroxyapatites (SiHA) are highly crystalline
bioceramics treated at high temperatures (about 1200 degrees C) which have been
approved for clinical use with spinal, orthopedic, periodontal, oral and
craniomaxillofacial applications. The preparation of SiHA with lower temperature
methods (about 700 degrees C) provides nanocrystalline SiHA (nano-SiHA) with
enhanced bioreactivity due to higher surface area and smaller crystal size. The
aim of this study has been to know the nanocrystallinity effects on the response
of both osteoblasts and osteoclasts (the two main cell types involved in bone
remodelling) to silicon substituted hydroxyapatite. EXPERIMENTS: Saos-2
osteoblasts and osteoclast-like cells (differentiated from RAW-264.7 macrophages)
have been cultured on the surface of nano-SiHA and SiHA disks and different cell
parameters have been evaluated: cell adhesion, proliferation, viability,
intracellular content of reactive oxygen species, cell cycle phases, apoptosis,
cell morphology, osteoclast-like cell differentiation and resorptive activity.
FINDINGS: This comparative in vitro study evidences that nanocrystallinity of
SiHA affects the cell/biomaterial interface inducing bone cell apoptosis by loss
of cell anchorage (anoikis), delaying osteoclast-like cell differentiation and
decreasing the resorptive activity of this cell type. These results suggest the
potential use of nano-SiHA biomaterial for preventing bone resorption in
treatment of osteoporotic bone.
PMID- 27497233
TI - Biomimetic membrane-conjugated graphene nanoarchitecture for light-manipulating
combined cancer treatment in vitro.
AB - We report that through facile lipid self-assembly, biomimetic membrane-conjugated
mesoporous silica-coated graphene oxide is constructed as targeting nanocarrier
toward efficient combination of photothermal therapy and chemotherapy.
Impressively, the simple surface modification with folate-contained lipid bilayer
allows the graphene-based nanoarchitecture above to be selectively internalized
by tumor cells overexpressing relevant receptors. Compared to pure drug, 7-fold
doxorubicin is delivered into tumor cells by the nanoarchitecture. After cellular
internalization, upon near infrared light illumination, graphene oxide in the
nanoarchitecture can convert light energy into heat to kill cancer cells
partially. Simultaneously, hyperthermia will drive rapid release of doxorubicin
from the nanoarchitecture above to further cause the death of more cancer cells.
Thus, integrated cancer treatment with higher efficacy is achieved in vitro
compared to that of individual therapy.
PMID- 27497234
TI - Evolution of camel CYP2E1 and its associated power of binding toxic industrial
chemicals and drugs.
AB - Camels are raised in harsh desert environment for hundreds of years ago. By
modernization of live and the growing industrial revolution in camels rearing
areas, camels are exposed to considerable amount of chemicals, industrial waste,
environmental pollutions and drugs. Furthermore, camels have unique gene
evolution of some genes to withstand living in harsh environments. In this work,
the camel cytochrome P450 2E1 (CYP2E1) is compromised to detect its evolution
rate and its power to bind with various chemicals, protoxins, procarcinogens,
industrial toxins and drugs. In comparison with human CYP2E1, camel CYP2E1 more
efficiently binds to small toxins as aniline, benzene, catechol, amides,
butadiene, toluene and acrylamide. Larger compounds were more preferentially
bound to the human CYP2E1 in comparison with camel CYP2E1. The binding of
inhalant anesthetics was almost similar in both camel and human CYP2E1 coinciding
with similar anesthetic effect as well as toxicity profiles. Furthermore,
evolutionary analysis indicated the high evolution rate of camel CYP2E1 in
comparison with human, farm and companion animals. The evolution rate of camel
CYP2E1 was among the highest evolution rate in a subset of 57 different
organisms. These results indicate rapid evolution and potent toxin binding power
of camel CYP2E1.
PMID- 27497235
TI - Regulatory T cells: balancing protection versus pathology.
AB - Foxp3+ regulatory T cells (Tregs) maintain immune tolerance, prevent autoimmunity
and modulate immune responses during infection and cancer. Recent studies have
revealed considerable heterogeneity and plasticity within the Treg compartment,
depending on the immunological context, which may result in Tregs losing their
suppressive function in inflammatory environments. We review how dysfunctional
Tregs contribute to disease pathogenesis in inflammatory conditions and how
inappropriate regulatory responses may hamper protective immunity in the context
of infection and cancer. We also discuss how Tregs might be targeted
therapeutically to re-establish a proper balance between regulatory and effector
responses in autoimmunity, infections, and cancer.
PMID- 27497237
TI - Hepatotoxicity of illegal home-made alcohols.
AB - OBJECTIVE AND AIM: Alcohol-related hepatotoxicity is not only caused by excessive
alcohol consumption but also caused and even accelerated by hepatotoxic
ingredients other than ethanol. Concentrations of hepatotoxic substances might be
significantly high, particularly in illegally produced home-made alcohols. In
this study we aim to analyze the hepatotoxic effects of a home-made alcohol
traditionally called "bogma raki" in Turkey. MATERIALS AND METHOD: Fifty Wistar
albino male rats were used. Five groups were randomly formed with ten animals in
each. Besides laboratory diets, groups were fed as follows: Group 1 (control
group) distilled water; Group 2 bogma raki with distilled water (%44 (v/v), 9.2
ml/kg/day); Group 3 bogma raki with distilled water (%44 (v/v), 9.2
ml/kg/day)+walnut (10 g/kg/day); Group 4 whisky with distilled water (%40 (v/v),
9.2 ml/kg/day); Group 5 distilled water + walnut (10 g/kg/day), for 28 days. The
toxicological analysis of The spirits were analyzed using Hewlett-Packard (Palo
Alto, CA) GC/MS system with HP 6890 gas chromatograph, an HP 5972 mass selective
detector (MSD) and an HP 6890 automatic liquid sampler GC/MS; the pressure of the
carrier gas helium was 6.0 bar and the split value with a ratio of 1:100. The
injection unit temperature set to 250 degrees C and MS quadrupole temperature
set to 280 degrees C. The MS quadrupole detector ionization energy set to 70 eV.
The initial column temperature was 60 degrees C (for 4 min) programmed by 6
degrees C/min to final temperature 160 degrees C and kept for 8 min at 160
degrees C. Utilized whisky and bogma raki samples were analyzed for the amounts
of trans-anethole, ethanol, methanol, 1-propanolol, butanol, 2-butanol, 2-methyl
1-propanolol (isobutanol) and 3-methylbutanol (isoamyl alcohol).
Histopathological changes in liver tissues were graded as follows; normal = 0
(<10%), mild = 1 (10%-40%), moderate = 2 (40%-70%), severe = 3 (above 70%).
RESULTS: Chemical composition of illegally produced raki sample (%v/v) was as
follows: trans-anethole %1.93, ethanol %95.70, 2-methyl-1-propanolol (isobutanol)
%0.19, asetic acid %0.25, 3-methylbutanol (isoamyl alcohol) %0.77, and others
%1.16. Chemical composition of commercial whisky sample (%v/v) was as follows:
ethanol %97.72, 2-methyl-1-propanolol (isobutanol) %0.57, asetic acid %0.23, 3
methylbutanol (isoamyl alcohol) %1.28, and others %0.2. No traces of trans
anethole were detected in whisky. Normal liver morphology was recorded in control
and walnut groups. However, bogma raki caused significant congestion and
inflammatory cell infiltration compared to control and walnut group. On the other
hand, whisky administration caused mild degeneration including inflammation in a
limited area. CONCLUSION: Obtained findings suggest that trans-anethole
containing alcoholic beverages are more hepatotoxic compared to commercial
alcoholic beverages.
PMID- 27497238
TI - Environmental contexts of combined alcohol and energy drink use: Associations
with intoxication in licensed venues.
AB - BACKGROUND: Environmental factors inside licensed venues have been found to
influence the intoxication levels and consumption practices of patrons. The
consumption of alcohol mixed with energy drinks (AmED) occurs primarily at or
prior to attending licensed venues, however there is a lack of in situ research
investigating AmED use in these contexts. Given that AmED use has been linked
with increased alcohol consumption, intoxication, illicit substance use, and risk
taking behaviours, this paper explores the environmental correlates and levels of
intoxication associated with AmED use in licensed venues. METHODS: Structured
observations were undertaken in five Australian cities on Friday and Saturday
nights. Covert teams spent 4-5h in venues and recorded hourly observations on
patron, venue, and staff characteristics, alcohol, illicit drug and AmED
consumption patterns and intoxication levels. RESULTS: 898 hourly observations
were recorded across 68 venues. All but one venue served energy drinks, and
patron AmED use was observed during 34.9% of hourly records. AmED use was more
prevalent after 12am and in nightclub venues compared to bars and pubs, and was
positively associated with high intoxication levels, illicit drug use, and
younger crowds. After controlling for environmental factors (i.e. venue crowding,
service practices, venue characteristics, patron demographics and behaviour) AmED
use did not predict high intoxication at a venue level in multivariable models.
CONCLUSION: AmED consumption is ubiquitous in the licensed venues of Australian
night-time entertainment districts, particularly busy nightclub venues where
intoxication and risky consumption are heightened. However, AmED use was not
associated with high patron intoxication when environmental factors were
considered.
PMID- 27497236
TI - Two anti-angiogenic TKI-PET tracers, [(11)C]axitinib and [(11)C]nintedanib:
Radiosynthesis, in vivo metabolism and initial biodistribution studies in
rodents.
AB - INTRODUCTION: Tyrosine kinase inhibitors (TKIs) are very attractive targeted
drugs, although a large portion of patients remains unresponsive. PET imaging
with EGFR targeting TKIs ([(11)C]erlotinib and [(18)F]afatinib) showed promise in
identifying treatment sensitive tumors. The aim of this study was to synthesize
two anti-angiogenic TKI tracers, [(11)C]axitinib and [(11)C]nintedanib, and to
evaluate their potential for PET. METHODS: Following successful tracer synthesis,
biodistribution studies in VU-SCC-OE and FaDu xenograft bearing mice were
performed. Furthermore, tracer stability studies in mice were performed employing
(radio-)HPLC and LC-MS/MS techniques. For [(11)C]nintedanib an LC-MS/MS method
was developed to detect the primary carboxylic acid metabolite, resulting from
methylester cleavage, in plasma and tumors, because this metabolite is postulated
to be important for nintedanib efficacy. LC-MS/MS was also explored to assess the
metabolic fate of [(11)C]axitinib in vivo, since axitinib has an isomerizable
double bond. RESULTS: [(11)C]axitinib and [(11)C]nintedanib were successfully
synthesized with 10.5+/-2.6% and 25.6+/-3.3% radiochemical yield (corrected for
decay), respectively. Biodistribution studies only demonstrated tumor uptake of
[(11)C]nintedanib in FaDu xenografts of 1.66+/-0.02% ID/g at 60min p.i. In vivo
stability analysis of [(11)C]axitinib at 45min p.i. revealed the formation of
predominantly non-polar metabolites (36.6+/-6.8% vs 47.1+/-8.4% of parent tracer
and 16.3+/-2.1% of polar metabolites), while for [(11)C]nintedanib mostly polar
metabolites were found (70.9+/-4.1 vs 26.7+/-3.9% of parent tracer and only 2.4+/
1.6 of a non-polar metabolites). No isomerization of [(11)C]axtinib was observed
in vivo; however, a sulfoxide metabolite could be detected using LC-MS/MS. For
[(11)C]nintedanib, LC-MS/MS revealed formation of the reported primary carboxylic
acid metabolite when in vitro plasma incubations were performed, with large
differences in plasmas from different species. In vivo metabolite analysis,
however, did not demonstrate the presence of the carboxylic acid in plasma or
tumor tissue. CONCLUSIONS: Reliable syntheses of [(11)C]axitinib and
[(11)C]nintedanib were successfully developed. Tumor uptake was observed for
[(11)C]nintedanib, albeit modest. The metabolic profiles of the tracers suggest
that rapid metabolism is partly responsible for the modest tumor targeting
observed.
PMID- 27497239
TI - Disulfide stress in carbon monoxide poisoning.
AB - OBJECTIVES: Carbon monoxide (CO) remains the most common cause of lethal
poisoning around the world. The purpose of this study was to investigate the
homeostasis between thiol-disulfide couples and to evaluate oxidative status
comprehensively in acute CO poisoning, using new parameters along with other well
known oxidant-antioxidant molecules. DESIGN AND METHODS: This case study
consisted of 43 subjects who were diagnosed with carbon monoxide poisoning and 35
healthy individuals who were used as controls. Thiol-disulfide paired tests were
examined in both groups using the method developed recently. RESULTS: Patients
with CO poisoning had significantly higher levels of serum disulfide than the
control patients (20.7+/-5.03 versus 16.43+/-3.97, p=0.001). Native thiol and
total thiol levels were lower in the CO patient group than in the control group
(p<0.001, for each variable). The disulfide/native thiol ratios and
disulfide/total thiol ratios were significantly higher, while native thiol/total
thiol ratios were significantly lower, in patients with acute CO poisoning than
in the healthy controls (p<0.001, for all ratios). The disulfide/native ratios
were negatively correlated with both total antioxidant response and paraoxonase
and arylesterase values and were positively correlated with total oxidant status
and ceruloplasmin values (p<0.05, for all correlations). CONCLUSIONS: Excessive
disulfide levels and their related ratios were found in CO poisoning patients. In
particular, the disulfide/native thiol ratio was identified as an indicator for
overall oxidative status. Among CO poisoning patients, the thiol-disulfide
balance was found to be impaired. Therefore, the disruption of thiol-disulfide
homeostasis might be involved in CO toxicity.
PMID- 27497240
TI - Identification and molecular characterisation of Lausanne Institutional Biobank
participants with familial hypercholesterolaemia - a proof-of-concept study.
AB - AIMS: We aimed to identify familial hypercholesterolaemia mutation carriers among
participants to the Lausanne Institutional Biobank (BIL). Our experimental
workflow was designed as a proof-of-concept demonstration of the resources and
services provided by our integrated institutional clinical research support
platform. METHODS: Familial hypercholesterolaemia was used as a model of a
relatively common yet often underdiagnosed and inadequately treated Mendelian
disease. Clinical and laboratory information was extracted from electronic
hospital records. Patients were selected using elevated plasma cholesterol levels
(total cholesterol >=7.5 mM or low-density lipoprotein cholesterol >=5 mM),
premature coronary artery disease status and age (18-60 yr) as main inclusion
criteria. LDLR, APOB and PCSK9 were analysed by high-throughput DNA sequencing.
The most relevant mutations were confirmed by Sanger sequencing. RESULTS: Of 23
737 patients contacted by the BIL, 17 760 individuals consented to participate
and 13 094 wished to be recontacted if there were findings requiring clinical
action. Plasma cholesterol records were available for 5111 participants, of whom
94 were selected for genetic screening. Twenty-five of the tested patients
presented with premature coronary artery disease while 69 had no such diagnosis.
Seven heterozygous carriers of eight rare coding missense variants were
identified. Three mutations were pathogenic (APOB p.R3527Q) or likely pathogenic
(LDLR p.C27W, LDLR p.P526S) for hypercholesterolaemia, while the others were
either benign or of unknown significance. One patient was a double heterozygote
for variants APOB p.R3527Q and LDLR p.P526S. CONCLUSION: This work illustrates
how clinical and translational research can benefit from a dedicated platform
integrating both a hospital-based biobank and a data support team.
PMID- 27497241
TI - Origin of year-long bean (Phaseolus dumosus Macfady, Fabaceae) from reticulated
hybridization events between multiple Phaseolus species.
AB - BACKGROUND AND AIMS: Improved understanding of the secondary gene pools of crops
is essential for advancing genetic gain in breeding programmes. Common bean,
Phaseolus vulgaris, is a staple crop with several wild relatives in its secondary
gene pool. The year-long bean, P. dumosus, an important crop in Guatemala, is
considered particularly closely related to P. vulgaris and a potential source of
novel variation. However, the genetic diversity and relationship to other
Phaseolus species of P. dumosus remain unclear. METHODS: We conducted the first
comprehensive investigation of P. dumosus genetic diversity using both nuclear
and chloroplast genome markers. Our nuclear marker set included over 700 markers
present within the Phaseolus DArT (Diversity Arrays Technology) array, which we
applied to P. dumosus and other relatives of P. vulgaris (including every
secondary gene pool species: P. acutifolius, P. albescens, P. coccineus and P.
costaricensis). KEY RESULTS: Phaseolus dumosus arose from hybridization of P.
vulgaris and P. coccineus, followed by at least two later hybridizations with
sympatric congener populations. Existing P. dumosus collections have low genetic
diversity. CONCLUSIONS: The under-utilized crop P. dumosus has a complex hybrid
origin. Further sampling in the region in which it arose may uncover additional
germplasm for introgressing favourable traits into crops within the P. vulgaris
gene pool.
PMID- 27497242
TI - CN-Wheat, a functional-structural model of carbon and nitrogen metabolism in
wheat culms after anthesis. I. Model description.
AB - BACKGROUND AND AIMS: Improving crops requires better linking of traits and
metabolic processes to whole plant performance. In this paper, we present CN
Wheat, a comprehensive and mechanistic model of carbon (C) and nitrogen (N)
metabolism within wheat culms after anthesis. METHODS: The culm is described by
modules that represent the roots, photosynthetic organs and grains. Each of them
includes structural, storage and mobile materials. Fluxes of C and N among
modules occur through a common pool and through transpiration flow. Metabolite
variations are represented by differential equations that depend on the
physiological processes occurring in each module. A challenging aspect of CN
Wheat lies in the regulation of these processes by metabolite concentrations and
the environment perceived by organs. KEY RESULTS: CN-Wheat simulates the
distribution of C and N into wheat culms in relation to photosynthesis, N uptake,
metabolite turnover, root exudation and tissue death. Regulation of physiological
activities by local concentrations of metabolites appears to be a valuable
feature for understanding how the behaviour of the whole plant can emerge from
local rules. CONCLUSIONS: The originality of CN-Wheat is that it proposes an
integrated view of plant functioning based on a mechanistic approach. The
formalization of each process can be further refined in the future as knowledge
progresses. This approach is expected to strengthen our capacity to understand
plant responses to their environment and investigate plant traits adapted to
changes in agronomical practices or environmental conditions. A companion paper
will evaluate the model.
PMID- 27497243
TI - CN-Wheat, a functional-structural model of carbon and nitrogen metabolism in
wheat culms after anthesis. II. Model evaluation.
AB - BACKGROUND AND AIMS: Simulating resource allocation in crops requires an
integrated view of plant functioning and the formalization of interactions
between carbon (C) and nitrogen (N) metabolisms. This study evaluates the
functional-structural model CN-Wheat developed for winter wheat after anthesis.
METHODS: In CN-Wheat the acquisition and allocation of resources between
photosynthetic organs, roots and grains are emergent properties of sink and
source activities and transfers of mobile metabolites. CN-Wheat was calibrated
for field plants under three N fertilizations at anthesis. Model parameters were
taken from the literature or calibrated on the experimental data. KEY RESULTS:
The model was able to predict the temporal variations and the distribution of
resources in the culm. Thus, CN-Wheat accurately predicted the post-anthesis
kinetics of dry masses and N content of photosynthetic organs and grains in
response to N fertilization. In our simulations, when soil nitrates were non
limiting, N in grains was ultimately determined by availability of C for root
activity. Dry matter accumulation in grains was mostly affected by photosynthetic
organ lifespan, which was regulated by protein turnover and C-regulated root
activity. CONCLUSIONS: The present study illustrates that the hypotheses
implemented in the model were able to predict realistic dynamics and spatial
patterns of C and N. CN-Wheat provided insights into the interplay of C and N
metabolism and how the depletion of mobile metabolites due to grain filling
ultimately results in the cessation of resource capture. This enabled us to
identify processes that limit grain mass and protein content and are potential
targets for plant breeding.
PMID- 27497244
TI - Foreword.
PMID- 27497247
TI - Does IQ = IQ? Comparability of Intelligence Test Scores in Typically Developing
Children.
AB - Numerous intelligence tests are available to psychological diagnosticians to
assess children's intelligence, but whether they yield comparable test results
has been little studied. We examined test scores of 206 typically developing
children aged 6 to 11 years on five German intelligence tests (Reynolds
Intellectual Assessment Scales; Snijders Oomen Nonverbal Intelligence Test;
Intelligence and Development Scales; Wechsler Intelligence Scale for Children,
4th edition; Culture Fair Intelligence Test Scale 2), which were individually
administered. On a sample level, the test scores showed strong correlation and
little or no mean difference. These results indicate that the tests measure a
similar underlying construct, which is interpreted as general intelligence. On an
individual level, however, test scores significantly differed across tests for
12% to 38% of the children. Differences did not depend on which test was used but
rather on unexplained error. Implications for the application of intelligence
assessment in psychological practice are discussed.
PMID- 27497248
TI - RUNX3-mediated up-regulation of miR-29b suppresses the proliferation and
migration of gastric cancer cells by targeting KDM2A.
AB - RUNX3 is a transcriptional factor that has been shown to regulate protein-coding
gene expression at the transcriptional level. However, the regulation of RUNX3 on
miRNAs is not fully understood. In this study, we used miRNA microarray to
identify the miRNAs that are regulated by RUNX3 and found that miR-29b showed the
most up-regulation in RUNX3 over-expressed cells compared with the control cells.
We used qRT-PCR to confirm the miRNA microarray results in several gastric cancer
cells and found that RUNX3 could bind to the miR-29b promoter directly and
cooperate with Smad3 to increase the promoter activity of miR-29b. In the
clinical setting, both RUNX3 and miR-29b are down-regulated significantly in
human gastric cancer tissues. A positive correlation between miR-29b and RUNX3
was found in the gastric cancer tissues. Additionally, we found that miR-29b
suppressed the proliferation and metastasis of gastric cancer cells by directly
targeting KDM2A. The miR-29b/KDM2A axis was involved in the RUNX3-mediated
inhibition of gastric cancer cell proliferation and metastasis. Taken together,
our results suggested that RUNX3-mediated up-regulation of miR-29b inhibited the
proliferation and migration of gastric cancer cells by targeting KDM2A,
representing a novel molecular mechanism for the tumor suppression action of
RUNX3.
PMID- 27497249
TI - Anxiety sensitivity and hazardous drinking among persons living with HIV/AIDS: An
examination of the role of emotion dysregulation.
AB - Hazardous drinking is prevalent among persons living with HIV/AIDS (PLWHA).
Anxiety sensitivity is a vulnerability factor that is highly associated with
hazardous drinking among seronegatives, but has yet to be tested in PLWHA.
Additionally, there is a need to examine potential mechanisms underlying
associations of anxiety sensitivity and hazardous drinking. Emotion dysregulation
is one potential construct that may explain the association between anxiety
sensitivity and hazardous drinking. The current study examined emotion
dysregulation as a potential explanatory variable between anxiety sensitivity and
four, clinically significant alcohol-related outcomes among PLWHA: hazardous
drinking, symptoms of alcohol dependence, number of days consuming alcohol within
the past month, and degree of past heavy episodic drinking. The sample included
126 PLWHA (Mage=48.3; SD=7.5; 65.9% male). Results indicated significant indirect
effects of anxiety sensitivity via emotion dysregulation in all models. Indirect
effects (kappa(2)) were of medium effect size. Alternative models were run
reversing the predictor with mediator and, separately, reversing the mediator
with the proposed outcome(s); alternative models yielded non-significant indirect
effects in all but one case. Together, the current results indicate that anxiety
sensitivity is associated emotion dysregulation, which, in turn, is associated
with hazardous drinking outcomes. Overall, these findings may provide initial
empirical evidence that emotion dysregulation may be a clinical intervention
target for hazardous drinking.
PMID- 27497250
TI - Biological therapies in lupus.
PMID- 27497252
TI - T-cell-directed therapies in systemic lupus erythematosus.
AB - Drug development for the treatment of systemic lupus erythematosus (SLE) has
largely focused on B-cell therapies. A greater understanding of the
immunopathogenesis of SLE coupled with advanced bioengineering has allowed for
clinical trials centered on other targets for SLE therapy. The authors discuss
the benefits and shortcomings of focusing on T-cell-directed therapies in SLE and
lupus nephritis clinical trials.
PMID- 27497253
TI - Targeted B cell therapies in the treatment of adult and pediatric systemic lupus
erythematosus.
AB - Belimumab (Benlysta) is a fully-humanized monoclonal antibody that inhibits B
lymphocyte stimulator (also known as B cell activating factor) and was approved
by the U.S. Federal Drug Administration and European Medicines Evaluation Agency
for treatment in adults with autoantibody-positive systemic lupus erythematosus
(SLE). Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody targeting
B lymphocytes. This review discusses the key findings of the phase III trials in
adults with SLE and of real-world use of belimumab and rituximab in the care of
both adult and pediatric SLE patients. It highlights the safety profile of
belimumab and rituximab and gives insight into the consideration of these
therapies for specific SLE disease states. It concludes with a discussion of the
current clinical trials investigating B cell therapies in specific SLE disease
states and a look to the future, with ongoing clinical trials.
PMID- 27497251
TI - Why targeted therapies are necessary for systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) continues to have important morbidity and
accelerated mortality despite therapeutic advances. Targeted therapies offer the
possibility of improved efficacy with fewer side effects. Current management
strategies rely heavily on nonspecific immunosuppressive agents. Prednisone, in
particular, is responsible for a considerable burden of later organ damage. There
are a multitude of diverse mechanisms of disease activity, immunogenic
abnormalities and clinical manifestations to take into consideration in SLE. Many
targeted agents with robust mechanistic preclinical data and promising early
phase studies have ultimately been disappointing in phase III, randomized,
controlled studies. Recent efforts have focused on B-cell therapies, in
particular given the success of belimumab in clinical trials, with limited
success. We remain optimistic regarding other specific therapies being evaluated,
including interferon-alpha blockade. It is likely that in SLE, given the
heterogeneity of the population involved, precision medicine is needed, rather
than expecting that any single biologic will be universally effective.
PMID- 27497254
TI - Interferon-targeted therapy in systemic lupus erythematosus: Is this an
alternative to targeting B and T cells?
AB - Clinical trials of investigational agents in systemic lupus erythematosus (SLE)
have focused on targeting dysregulated B and T cells; however, recent
translational research findings of the importance of the dysregulation of the
innate immune system in SLE have led to clinical trials that target interferon.
Three biologics that target type I interferons have been tested for their
efficacy and safety in active SLE patients; these phase II trials have tested the
hypothesis that down-regulation of interferon-regulated gene expression (the
interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti
interferon-alpha monoclonal antibody, was studied in patients who had
discontinued immunosuppressants. This study failed to show efficacy as assessed
by both two outcome assessments; however, in low interferon signature patients,
response was higher and corticosteroid usage was less in rontalizumab-treated
patients. Sifalimumab, another anti-interferon-alpha monoclonal antibody, was
studied in patients who remained on standard of care therapy. This study showed
significantly better efficacy in patients treated with two sifalimumab dosages;
significant differences were seen in the high interferon signature group. In a
similar design and in a similar population as the sifalimumab study, anifrolumab,
a monoclonal antibody that binds to a type I interferon receptor, was studied in
patients who remained on standard of care therapy. In this study, one dosage
group demonstrated efficacy and statistically significant effects were achieved
in both tested dosage groups with secondary end points. Oral corticosteroid
reduction to <=7.5 mg daily was achieved in one of the tested dosage groups and
organ-specific outcomes were significantly improved in that same group. For all
studies, no significant differences in serious adverse effects were seen;
although, herpes zoster infections were increased in sifalimumab- and anifrolumab
treated patients and influenza rates were increased in anifrolumab-treated
patients. Anifrolumab is currently in pivotal phase III studies. Data appear to
support the concept that targeting type I interferon in SLE patients associates
with clinical efficacy and safety. Further data are forthcoming from ongoing
phase III clinical trials of anifrolumab. Other drug development efforts should
be considered that target plasmacytoid dendritic cells and toll like receptors
given the effects these components have on interferon production.
PMID- 27497255
TI - Rethinking biologics in lupus nephritis.
AB - Lupus nephritis (LN) is a chronic and devastating complication of systemic lupus
erythematosus. Despite advances in our understanding of LN and the availability
of effective therapies, LN remains a difficult clinical problem, and progression
to end stage renal disease remains a significant challenge. Though the advent of
biologics has revolutionized the treatment of many rheumatological conditions,
and several clinical trials of biologics have been conducted in LN, the promise
of biologics remains unfulfilled. The experience gained from these initial
clinical trials can help tailor approaches in future clinical trials, and the
lessons learned can be applied to find a cure for this condition.
PMID- 27497246
TI - The intestinal microbiome and surgical disease.
PMID- 27497256
TI - Patient-reported outcomes in lupus clinical trials with biologics.
AB - Therapeutic advances in systemic lupus erythematosus (SLE) are greatly needed.
Despite advances in our knowledge of pathogenesis of the disease and targets,
treatment remains a significant challenge. Finding effective and relatively safe
medications remains one of the top priorities. SLE significantly impairs quality
of life (QoL), and patient-reported outcomes (PROs) measure a unique aspect of
the disease not captured by disease activity. Inclusion of PRO measurements is
encouraged in SLE clinical trials, as they allow capturing benefits of a proposed
intervention in language patients can relate to and in areas deemed pertinent and
important to and by patients. Availability of patient-reported and patient
centric clinical trials data may facilitate patients in informed and shared
decision making, and allow for comparative cost-effectiveness evaluation for
future resource allocation and reimbursements. Herein we review clinical trials
with biologic therapies wherein PRO tools were included in the study design.
PMID- 27497258
TI - Improved strategies for designing lupus trials with targeted therapies: learning
from 65 years of experience.
AB - The development of new agents to manage lupus erythematosus has lagged behind
other autoimmune rheumatic diseases. This is in large part because lupus is a
heterogeneous disorder affecting nine principal domains (organ systems) that are
difficult to measure and quantify and can be at variance with each other. Over
the last two decades, a variety of guidelines, definitions, candidate surrogate
or biomarkers, metrics and composite indices have been presented as benchmarks
that can be utilized to assess lupus in clinical trials. Despite this, over 20
agents have failed to achieve their primary outcome measure, some of which are
generally believed to be clinically effective. This article presents constructive
suggestions and improved strategies in trial design that will hopefully lead to
the introduction of new agents for the disease.
PMID- 27497257
TI - A critical review of clinical trials in systemic lupus erythematosus.
AB - One challenge in caring for patients with systemic lupus erythematosus (SLE) is a
paucity of approved therapeutics for treatment of the diverse disease
manifestations. In the last 60 years, only one drug, belimumab, has been approved
for SLE treatment. Critical evaluation of investigator initiated and pharma
sponsored randomized controlled trials (RCTs) highlights barriers to successful
drug development in SLE, including disease heterogeneity, inadequate trial size
or duration, insufficient dose finding before initiation of large trials,
handling of background medications, and choice of primary endpoint. Herein we
examine lessons learned from landmark SLE RCTs and subsequent advances in trial
design, as well as discuss efforts to address limitations in current SLE outcome
measures that will improve detection of true therapeutic responses in future
RCTs.
PMID- 27497259
TI - Drug repositioning in SLE: crowd-sourcing, literature-mining and Big Data
analysis.
AB - Lupus patients are in need of modern drugs to treat specific manifestations of
their disease effectively and safely. In the past half century, only one new
treatment has been approved by the US Food and Drug Administration (FDA) for
systemic lupus erythematosus (SLE). In 2014-2015, the FDA approved 71 new drugs,
only one of which targeted a rheumatic disease and none of which was approved for
use in SLE. Repositioning/repurposing drugs approved for other diseases using
multiple approaches is one possible means to find new treatment options for lupus
patients. "Big Data" analysis approaches this challenge from an unbiased
standpoint whereas literature mining and crowd sourcing for candidates assessed
by the CoLTs (Combined Lupus Treatment Scoring) system provide a hypothesis-based
approach to rank potential therapeutic candidates for possible clinical
application. Both approaches mitigate risk since the candidates assessed have
largely been extensively tested in clinical trials for other indications. The
usefulness of a multi-pronged approach to drug repositioning in lupus is
highlighted by orthogonal confirmation of hypothesis-based drug repositioning
predictions by "Big Data" analysis of differentially expressed genes from lupus
patient samples. The goal is to identify novel therapies that have the potential
to affect disease processes specifically. Involvement of SLE patients and the
scientists that study this disease in thinking about new drugs that may be
effective in lupus though crowd-sourcing sites such as LRxL-STAT
(www.linkedin.com/in/lrxlstat) is important in stimulating the momentum needed to
test these novel drug targets for efficacy in lupus rapidly in small, proof-of
concept trials conducted by LuCIN, the Lupus Clinical Investigators Network
(www.linkedin.com/in/lucinstat).
PMID- 27497260
TI - Patient and general public preferences for health states: A call to reconsider
current guidelines.
AB - In economic evaluations of health care interventions, benefits are often
expressed in terms of Quality-Adjusted Life-Years (QALYs). The QALY comprises
length and quality of life into one measure which allows cross-disease
comparability. The quality adjustment of the QALY is based on preferences for
health states. An important normative choice is the question whose preferences
for states of health we wish to capture. The answer to this question is directly
related to the normative question regarding the appropriate maximand in health
care decisions. Currently, preferences are commonly derived from the general
public, rather than from actual patients. This choice, which can have large
consequences on final outcomes of economic evaluations, has always been a topic
of debate. This paper clarifies and furthers the discussion regarding the
appropriate source of preferences for health state valuations, acknowledges the
plurality of different perspectives, and argues that health economic guidelines
could require analysis of benefit in terms of QALYs based on both patient and
general public preferences.
PMID- 27497261
TI - Partial hessian fitting for determining force constant parameters in molecular
mechanics.
AB - We present a new protocol for deriving force constant parameters that are used in
molecular mechanics (MM) force fields to describe the bond-stretching, angle
bending, and dihedral terms. A 3 * 3 partial matrix is chosen from the MM Hessian
matrix in Cartesian coordinates according to a simple rule and made as close as
possible to the corresponding partial Hessian matrix computed using quantum
mechanics (QM). This partial Hessian fitting (PHF) is done analytically and thus
rapidly in a least-squares sense, yielding force constant parameters as the
output. We herein apply this approach to derive force constant parameters for the
AMBER-type energy expression. Test calculations on several different molecules
show good performance of the PHF parameter sets in terms of how well they can
reproduce QM-calculated frequencies. When soft bonds are involved in the target
molecule as in the case of secondary building units of metal-organic frameworks,
the MM-optimized geometry sometimes deviates significantly from the QM-optimized
one. We show that this problem is rectified effectively by use of a simple
procedure called Katachi that modifies the equilibrium bond distances and angles
in bond-stretching and angle-bending terms. (c) 2016 Wiley Periodicals, Inc.
PMID- 27497262
TI - TAK1 adaptor proteins, TAB2 and TAB3, link the signalosome to B-cell receptor
induced IKK activation.
AB - Transforming growth factor-beta-activated kinase (TAK)1-binding proteins (TAB)
activate nuclear factor-kappaB by linking TAK1 to signaling molecules. We
investigated the mechanisms underlying B-cell receptor (BCR) signaling in TAB2-
and TAB3-deficient and TAB3 domain deletion mutant DT40 B cell lines. Loss of
TAB2 and TAB3 abolished BCR-induced inhibitor of kappaB kinase (IKK) activation
and TAK1 binding to caspase recruitment domain membrane-associated guanylate
kinase protein (CARMA)1. Deletion of TAB3, coupling of ubiquitin conjugation to
ER degradation, coiled-coil, and zinc finger domains blocked IKK activation and
association with CARMA1. Thus, TAB2 and TAB3 connect signaling molecules that
activate IKK in BCR signaling.
PMID- 27497263
TI - Quality of life in stabilized patients with schizophrenia is mainly associated
with resilience and self-esteem.
AB - OBJECTIVE: Improving quality of life (QoL) is an important objective in the
treatment of schizophrenia. The aim of the current study was to examine to what
extent resilience, self-esteem, hopelessness, and psychopathology are correlated
with QoL. METHOD: We recruited 52 out-patients diagnosed with schizophrenia
according to DSM-IV criteria and 77 healthy control subjects from the general
community. In patients, psychopathology was quantified by the Positive and
Negative Syndrome Scale. The following scales were used in both patients and
control subjects: the Berliner Lebensqualitatsprofil, the Resilience Scale, the
Rosenberg Self-Esteem Scale, and the Beck Hopelessness Scale to assess QoL,
resilience, self-esteem, and hopelessness respectively. RESULTS: Patients with
schizophrenia presented with significantly less QoL, resilience, self-esteem, and
hope compared to healthy control subjects. In patients, QoL correlated moderately
with resilience, self-esteem, and hopelessness and weakly with symptoms. With
respect to the latter, particularly depression and positive symptoms were
negatively correlated with QoL. CONCLUSION: Our results highlight the complex
nature of QoL in patients suffering from schizophrenia. They underscore that
significant efforts are necessary to enhance resilience and self-esteem and to
diminish hopelessness as well as affective and positive symptoms in patients with
schizophrenia.
PMID- 27497265
TI - Risk of sensorineural hearing loss with macrolide antibiotics: A nested case
control study.
AB - OBJECTIVES: To determine the association between a diagnosis of sensorineural
hearing loss (SNHL) and the prescription of a macrolide antibiotic. STUDY DESIGN:
Retrospective nested case-control study. METHODS: From the LifeLink (IMS,
Danbury, CT) health claims database, we randomly selected a cohort of subjects 15
to 60 years old from 2006 to 2014. Cases were identified as patients diagnosed
with SNHL, each matched by age and calendar time to 10 controls selected from the
same cohort. All macrolide prescriptions (erythromycin, azithromycin,
clarithromycin, and telithromycin) were identified, and statistical comparison of
usage was compared between cases and controls. Amoxicillin and fluoroquinolone
antibiotics were used as positive controls to further investigate confounding by
infection. Albuterol was used as a negative control because this is a drug class
not expected to be associated with SNHL or with a confounding condition
potentially causing SNHL. RESULTS: From a cohort of 6,110,723 subjects, we
identified 5,989 cases of SNHL and 59,890 corresponding controls. The rate ratio
for one prescription of a macrolide was 1.36 (95% confidence inteval [CI]: 1.24
1.49) and for multiple prescriptions was 1.66 (95% CI: 1.42-1.94). Similar rate
ratios were observed with multiple prescriptions of amoxicillin and
fluoroquinolones. CONCLUSION: A significant association between SNHL and
macrolide use was likely due to confounding by indication for antibiotic
treatment because the risk was also observed with fluoroquinolones and
amoxicillin, antibiotics with no known ototoxic potential. Therefore, there does
not appear to be an increased risk of SNHL in patients treated with macrolide
antibiotics. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:229-232, 2017.
PMID- 27497264
TI - Identification of a combined biomarker for malignant transformation in oral
submucous fibrosis.
AB - BACKGROUND: Oral submucous fibrosis (OSF) is a chronic progressive disease of the
oral cavity that is considered a common potentially malignant disorder in South
Asia. Areca nut chewing is the main etiological factor, but its carcinogenic
mechanism has yet to be proven. The purpose of this study was to identify the
useful biomarkers in predicting high-risk patients with OSF. METHODS: Thirty-six
cases of OSF and six cases of normal oral mucosa (NOM) were used for this study.
Immunohistochemical staining was performed for Ki67, cyclin D1, p16, p53, beta
catenin, c-Jun, c-Met, and insulin-like growth factor II mRNA-binding protein 3
(IMP3). The expression patterns of NOM served as guidelines for the scoring
system. RESULTS: The expression of Ki67, cyclin D1, c-Met, IMP3, and beta-catenin
showed a significant difference between OSF and NOM samples. The combined
biomarkers of Ki67 and p16 showed significantly different expression between the
transformation and non-transformation groups. With discriminant analysis, we
proposed a noble formula and cutoff value for predicting high-risk patients with
OSF. CONCLUSION: The notable biomarkers in our present study were Ki67 and p16
showing significantly different expression levels between the transformation and
non-transformation groups. With the identification of high-risk patients with
OSF, we can expect to develop more intensive treatment modalities, leading to the
reduction in cancer transformation rate from OSF.
PMID- 27497266
TI - Effect of polishing instruments and polishing regimens on surface topography and
phase transformation of monolithic zirconia: An evaluation with XPS and XRD
analysis.
AB - PURPOSE: Polishing procedures might alter monolithic zirconia (MZ) surface
resulting in phase changes that can be deleterious for clinical performance and
antagonist tooth wear. This study investigated the topographical features and
phase transformation in MZ after polishing with different regimens simulating the
clinical workflow. MATERIALS AND METHODS: MZ specimens (Katana Zirconia HT,
Kuraray-Noritake) (12*12*1.8 mm(3)) were grinded and polished using one of the
five systems assessed: BG: Silicone carbide polishers (Brownie, Greenie, Super
Greenie); CG: Diamond impregnated ceramic polisher kit (Ceragloss); EV:
Synthetically bonded grinder interspersed with diamond (EVE Kit); SL: Urethane
coated paper with aluminium oxide grits (Soflex Finishing and Polishing System
Kit) and DB: Diamond bur (8 um). Polished specimens were initially roughened with
220 um diamond burs (Grinding Bur-GB) (10 s, 160.000160,000 rpm) and considered
for baseline measurements. Polishing regimens were performed for 10 s using a
slow-speed hand piece under water-cooling except for SL, in a custom made device
(750 g; 5000 and 75,000 rpm). Surface roughnesses, phase changes (XRD) were
assessed, surface characterization was performed (SEM, EDS). RESULTS: The highest
roughness was obtained with the EV system (1.11 um) compared to those of other
systems (0.13-0.4 um) (ptheta and minor peak at 34.94 degrees 2theta. While GB,
CG, EV, SL and DB exhibited a peak shift to the left, BG demonstrated a right
peak shift on the 2theta scale. Monoclinic phase change was not noted in any of
the groups. CONCLUSION: All polishing methods, except BG, exhibited a peak shift
towards the lower angles of the 2-theta scale. Since the peak shifts were in the
order of fractions of an angle they are attributed to stress formation rather
than a phase change in the material. Thus, all polishing systems tested may not
be detrimental for the phase transformation of MZ. EV system resulted in the
highest roughness and none of the polishing regimens restored the polishability
to the baseline level.
PMID- 27497267
TI - Laryngeal ultrasound and pediatric vocal fold nodules.
AB - OBJECTIVES/HYPOTHESIS: The term vocal fold nodules refers to bilateral thickening
of the membranous folds with minimal impairment of the vibratory properties of
the mucosa. Nodules are thought to be related to repetitive mechanical stress,
associated with voice use patterns. Diagnosis is typically made in the office via
either rigid or flexible laryngeal stroboscopy. Depending on the individual
child, obtaining an optimal view of the larynx can be difficult if not
impossible. Recent advances in high-frequency ultrasonography allows for
transcervical examination of laryngeal structures. The goal of this project was
to determine if laryngeal ultrasound (LUS) can be used to identify vocal fold
nodules in dysphonic children. STUDY DESIGN: Prospective case-control study in
which the patient acted as his or her own control. METHODS: Forty-six pediatric
patients were recruited for participation in this study; the mean age was 4.8
years. Twenty-three did not have any vocal fold lesions and 23 had a diagnosis of
vocal fold nodules on laryngeal stroboscopy. Recorded LUSs were reviewed by two
pediatric radiologists who were blinded to the nodule status. RESULTS: There was
substantial inter-rater agreement (kappa = 0.70, 95% confidence interval [CI]:
0.50-0.89) between the two radiologists regarding the presence of nodules. There
was also substantial agreement (kappa = 0.87, 95% CI: 0.72-1) between LUS and
laryngeal stroboscopy. Sensitivity of LUS was 100% (95% CI: 85%-100%) and
specificity was 87% (95% CI: 66%-97%). CONCLUSIONS: LUS can be used to identify
vocal fold nodules in children with substantial agreement with laryngeal
stroboscopy. LEVEL OF EVIDENCE: 3b Laryngoscope, 127:676-678, 2017.
PMID- 27497268
TI - Integrated molecular and bioprocess engineering for bacterially produced
immunogenic modular virus-like particle vaccine displaying 18 kDa rotavirus
antigen.
AB - A high global burden of rotavirus disease and the unresolved challenges with the
marketed rotavirus vaccines, particularly in the developing world, have ignited
efforts to develop virus-like particle (VLP) vaccines for rotavirus. While
rotavirus-like particles comprising multiple viral proteins can be difficult to
process, modular VLPs presenting rotavirus antigenic modules are promising
alternatives in reducing process complexity and cost. In this study, integrated
molecular and bioprocess engineering approaches were used to simplify the
production of modular murine polyomavirus capsomeres and VLPs presenting a
rotavirus 18 kDa VP8* antigen. A single construct was generated for dual
expression of non-tagged murine polyomavirus capsid protein VP1 and modular VP1
inserted with VP8*, for co-expression in Escherichia coli. Co-expressed proteins
assembled into pentameric capsomeres in E. coli. A selective salting-out
precipitation and a polishing size exclusion chromatography step allowed the
recovery of stable modular capsomeres from cell lysates at high purity, and
modular capsomeres were successfully translated into modular VLPs when assembled
in vitro. Immunogenicity study in mice showed that modular capsomeres and VLPs
induced high levels of VP8*-specific antibodies. Our results demonstrate that a
multipronged synthetic biology approach combining molecular and bioprocess
engineering enabled simple and low-cost production of highly immunogenic modular
capsomeres and VLPs presenting conformational VP8* antigenic modules. This
strategy potentially provides a cost-effective production route for modular
capsomere and VLP vaccines against rotavirus, highly suitable to manufacturing
economics for the developing world. Biotechnol. Bioeng. 2017;114: 397-406. (c)
2016 Wiley Periodicals, Inc.
PMID- 27497269
TI - Population modeling for pesticide risk assessment of threatened species-A case
study of a terrestrial plant, Boltonia decurrens.
AB - Although population models are recognized as necessary tools in the ecological
risk assessment of pesticides, particularly for species listed under the
Endangered Species Act, their application in this context is currently limited to
very few cases. The authors developed a detailed, individual-based population
model for a threatened plant species, the decurrent false aster (Boltonia
decurrens), for application in pesticide risk assessment. Floods and competition
with other plant species are known factors that drive the species' population
dynamics and were included in the model approach. The authors use the model to
compare the population-level effects of 5 toxicity surrogates applied to B.
decurrens under varying environmental conditions. The model results suggest that
the environmental conditions under which herbicide applications occur may have a
higher impact on populations than organism-level sensitivities to an herbicide
within a realistic range. Indirect effects may be as important as the direct
effects of herbicide applications by shifting competition strength if competing
species have different sensitivities to the herbicide. The model approach
provides a case study for population-level risk assessments of listed species.
Population-level effects of herbicides can be assessed in a realistic and species
specific context, and uncertainties can be addressed explicitly. The authors
discuss how their approach can inform the future development and application of
modeling for population-level risk assessments of listed species, and ecological
risk assessment in general. Environ Toxicol Chem 2017;36:480-491. (c) 2016 SETAC.
PMID- 27497270
TI - Does adaptive radiation of a host lineage promote ecological diversity of its
bacterial communities? A test using gut microbiota of Anolis lizards.
AB - Adaptive radiations provide unique opportunities to test whether and how recent
ecological and evolutionary diversification of host species structures the
composition of entire bacterial communities. We used 16S rRNA gene sequencing of
faecal samples to test for differences in the gut microbiota of six species of
Puerto Rican Anolis lizards characterized by the evolution of distinct
'ecomorphs' related to differences in habitat use. We found substantial variation
in the composition of the microbiota within each species and ecomorph (trunk
crown, trunk-ground, grass-bush), but no differences in bacterial alpha diversity
among species or ecomorphs. Beta diversity analyses revealed subtle but
significant differences in bacterial composition related to host phylogeny and
species, but these differences were not consistently associated with Anolis
ecomorph. Comparison of a trunk-ground species from this clade (A. cristatellus)
with a distantly related member of the same ecomorph class (A. sagrei) where the
two species have been introduced and are now sympatric in Florida revealed
pronounced differences in the alpha diversity and beta diversity of their
microbiota despite their ecological similarity. Comparisons of these populations
with allopatric conspecifics also revealed geographic differences in bacterial
alpha diversity and beta diversity within each species. Finally, we observed high
intraindividual variation over time and strong effects of a simplified laboratory
diet on the microbiota of A. sagrei. Collectively, our results indicate that
bacterial communities are only weakly shaped by the diversification of their
lizard hosts due to the strikingly high levels of bacterial diversity and
variation observed within Anolis species.
PMID- 27497271
TI - Avoiding long-term muscle damage upon ischaemia-reperfusion.
PMID- 27497273
TI - Fit for Purpose, Psychometric Assessment of the Eating Attitudes Test-26 in an
Irish Adolescent Sample.
AB - The present study examined the psychometric properties of the Eating Attitudes
Test-26 (EAT-26) in a sample of Irish adolescents (N=2444). Consistent with
previous research, in adolescents, confirmatory factor analysis (CFA) failed to
replicate the original three-factor structure of the EAT-26. Goodness-of-fit
indices provided support for a recently published six-factor EAT-18 model. As the
EAT-26 is typically used as a unitary measure by clinicians, a second-order
factor model was investigated, which supported a general concept of eating
problems. Convergent validity of the EAT-18 was assessed using the Eating
Disorder Inventory-3 (EDI-3). Using the 90th percentile, a cut-off score of 13
was identified on the EAT-18 that discriminated between those indicative and non
indicative of disordered eating attitudes and behaviors. Findings suggest that
the revised factor structures may be more suitable for the general adolescent
population than the original three-factor EAT-26. Clinical implications of the
EAT-18 and future research recommendations are addressed.
PMID- 27497274
TI - Validation of the Behaviour Rating Inventory of Executive Function - Adult
Version (BRIEF-A) in the obese with and without binge eating disorder.
AB - Obesity and binge eating disorder (BED) are both associated with deficiencies in
executive function. The Behaviour Rating Inventory of Executive Function - Adult
Version (BRIEF-A) is a self-report measure that assesses executive function. This
study aimed to examine the psychometric properties of the BRIEF-A in an obese
population, with and without BED, and to explore the differences on the BRIEF-A
in the obese, with and without BED, compared to normative sample. 98 obese
participants (70 BED) completed the BRIEF-A, DASS-21 and several performance
based measures of executive function. 30 participants completed a repeat
assessment two months later. There was evidence of good internal consistency and
test-retest reliability, however evidence for construct and convergent validity
was mixed. Additionally, it was found that obese individuals report significantly
more executive function difficulties on the BRIEF-A than the normative sample.
Further, obese with BED report more executive function difficulties than those
without. This study shows some evidence of sound psychometric properties of the
BRIEF-A in an obese sample, however more research is required to understand the
nature of executive function being measured.
PMID- 27497272
TI - Integrating metabolomics and transcriptomics data to discover a biocatalyst that
can generate the amine precursors for alkamide biosynthesis.
AB - The Echinacea genus is exemplary of over 30 plant families that produce a set of
bioactive amides, called alkamides. The Echinacea alkamides may be assembled from
two distinct moieties, a branched-chain amine that is acylated with a novel
polyunsaturated fatty acid. In this study we identified the potential
enzymological source of the amine moiety as a pyridoxal phosphate-dependent
decarboxylating enzyme that uses branched-chain amino acids as substrate. This
identification was based on a correlative analysis of the transcriptomes and
metabolomes of 36 different E. purpurea tissues and organs, which expressed
distinct alkamide profiles. Although no correlation was found between the
accumulation patterns of the alkamides and their putative metabolic precursors
(i.e., fatty acids and branched-chain amino acids), isotope labeling analyses
supported the transformation of valine and isoleucine to isobutylamine and 2
methylbutylamine as reactions of alkamide biosynthesis. Sequence homology
identified the pyridoxal phosphate-dependent decarboxylase-like proteins in the
translated proteome of E. purpurea. These sequences were prioritized for direct
characterization by correlating their transcript levels with alkamide
accumulation patterns in different organs and tissues, and this multi-pronged
approach led to the identification and characterization of a branched-chain amino
acid decarboxylase, which would appear to be responsible for generating the amine
moieties of naturally occurring alkamides.
PMID- 27497275
TI - Multidisciplinary interventions in the management of atopic dermatitis.
AB - Atopic dermatitis (AD) is the most common pediatric skin disease. AD has a
significant effect on patient and family quality of life caused by intense
pruritus, sleep disruption, dietary and nutritional concerns, and psychological
stress associated with the disease and its management. Multidisciplinary
approaches to AD care have been developed in appreciation of the complex
interplay among biological, psychological, behavioral, and dietary factors that
affect disease control and the wide range of knowledge, skills, and support that
patients and families require to effectively manage and cope with this condition.
Common components of multidisciplinary treatment approaches include medical
evaluation and management by an AD specialist, education and nursing care,
psychological and behavioral support, and nutritional assessment and guidance.
Models of care include both clinical programs and structured educational groups
provided as adjuncts to standard clinical care. Available evidence suggests
beneficial effects of multidisciplinary interventions in improving disease
severity and quality of life, particularly for patients with moderate-to-severe
disease. Additional research is needed to identify the best candidates for the
various multidisciplinary approaches and evaluate the cost-effectiveness of these
programs.
PMID- 27497276
TI - Cellular and molecular immunologic mechanisms in patients with atopic dermatitis.
AB - Atopic dermatitis (AD) is a complex skin disease frequently associated with other
diseases of the atopic diathesis. Recent evidence supports the concept that AD
can also recognize other comorbidities, such as chronic inflammatory bowel or
cardiovascular diseases. These comorbidities might result from chronic cutaneous
inflammation or from a common, yet-to-be-defined immunologic background leading
to immune deviations. The activation of immune cells and their migration to the
skin play an essential role in the pathogenesis of AD. In patients with AD, an
underlying immune deviation might result in higher susceptibility of the skin to
environmental factors. There is a high unmet medical need to define immunologic
endotypes of AD because it has significant implications on upcoming
stratification of the phenotype of AD and the resulting targeted therapies in the
development of precision medicine. This review article emphasizes studies on
environmental factors affecting AD development and novel biological agents used
in the treatment of AD. Best evidence of the clinical efficacy of novel
immunologic approaches using biological agents in patients with AD is available
for the anti-IL-4 receptor alpha-chain antibody dupilumab, but a number of
studies are currently ongoing with other specific antagonists to immune system
players. These targeted molecules can be expressed on or drive the cellular
players infiltrating the skin (eg, T lymphocytes, dendritic cells, or
eosinophils). Such approaches can have immunomodulatory and thereby beneficial
clinical effects on the overall skin condition, as well as on the underlying
immune deviation that might play a role in comorbidities. An effect of these
immunologic treatments on pruritus and the disturbed microbiome in patients with
AD has other potential consequences for treatment.
PMID- 27497277
TI - Multifactorial skin barrier deficiency and atopic dermatitis: Essential topics to
prevent the atopic march.
AB - Atopic dermatitis (AD) is the most common inflammatory skin disease in the
industrialized world and has multiple causes. Over the past decade, data from
both experimental models and patients have highlighted the primary pathogenic
role of skin barrier deficiency in patients with AD. Increased access of
environmental agents into the skin results in chronic inflammation and
contributes to the systemic "atopic (allergic) march." In addition, persistent
skin inflammation further attenuates skin barrier function, resulting in a
positive feedback loop between the skin epithelium and the immune system that
drives pathology. Understanding the mechanisms of skin barrier maintenance is
essential for improving management of AD and limiting downstream atopic
manifestations. In this article we review the latest developments in our
understanding of the pathomechanisms of skin barrier deficiency, with a
particular focus on the formation of the stratum corneum, the outermost layer of
the skin, which contributes significantly to skin barrier function.
PMID- 27497278
TI - Advances in asthma 2015: Across the lifespan.
AB - In 2015, progress in understanding asthma ranged from insights to asthma
inception, exacerbations, and severity to advancements that will improve disease
management throughout the lifespan. 2015's insights to asthma inception included
how the intestinal microbiome affects asthma expression with the identification
of specific gastrointestinal bacterial taxa in early infancy associated with less
asthma risk, possibly by promoting regulatory immune development at a critical
early age. The relevance of epigenetic mechanisms in regulating asthma-related
gene expression was strengthened. Predicting and preventing exacerbations
throughout life might help to reduce progressive lung function decrease and
disease severity in adulthood. Although allergy has long been linked to asthma
exacerbations, a mechanism through which IgE impairs rhinovirus immunity and
underlies asthma exacerbations was demonstrated and improved by anti-IgE therapy
(omalizumab). Other key molecular pathways underlying asthma exacerbations, such
as cadherin-related family member 3 (CDHR3) and orosomucoid like 3 (ORMDL3), were
elucidated. New anti-IL-5 therapeutics, mepolizumab and reslizumab, were US Food
and Drug Administration approved for the treatment of patients with severe
eosinophilic asthma. In a clinical trial the novel therapeutic inhaled GATA3 mRNA
specific DNAzyme attenuated early- and late-phase allergic responses to inhaled
allergen. These current findings are significant steps toward addressing unmet
needs in asthma prevention, severity modification, disparities, and lifespan
outcomes.
PMID- 27497279
TI - Assessing the effect of engineered nanomaterials on the environment and human
health.
PMID- 27497280
TI - Asthma and the Olympics.
PMID- 27497282
TI - Dendritic cell targeting with C-type lectins for improvement of allergen
immunotherapy.
PMID- 27497283
TI - A touchscreen based global motion perception task for mice.
AB - Global motion perception is a function of higher, or extrastriate, visual system
circuitry. These circuits can be engaged in visually driven navigation, a
behavior at which mice are adept. However, the properties of global motion
perception in mice are unclear. Therefore, we developed a touchscreen-based, two
alternative forced choice (2AFC) task to explore global motion detection in mice
using random dot kinematograms (RDK). Performance data was used to compute
coherence thresholds for global motion perception. The touchscreen-based task
allowed for parallel training and testing with multiple chambers and minimal
experimenter intervention with mice performing hundreds of trials per session.
Parameters of the random dot kinematograms, including dot size, lifetime, and
speed, were tested. Mice learned to discriminate kinematograms whose median
motion direction differed by 90 degrees in 7-24days after a 10-14day pre-training
period. The average coherence threshold (measured at 70% correct) in mice for
this task was 22+/-5%, with a dot diameter of 3.88mm and speed of 58.2mm/s. Our
results confirm the ability of mice to perform global motion discriminations, and
the touchscreen assay provides a flexible, automated, and relatively high
throughput method with which to probe complex visual function in mice.
PMID- 27497284
TI - The Cytokine CXCL12 Promotes Basket Interneuron Inhibitory Synapses in the Medial
Prefrontal Cortex.
AB - Prenatally, the cytokine CXCL12 regulates cortical interneuron migration, whereas
its postnatal functions are poorly understood. Here, we report that CXCL12 is
expressed postnatally in layer V pyramidal neurons and localizes on their cell
bodies in the medial prefrontal cortex (mPFC), while its receptors CXCR4/CXCR7
localize to the axon terminals of parvalbumin (PV) interneurons. Conditionally
eliminating CXCL12 in neonatal layer V pyramidal neurons led to decreased axon
targeting and reduced inhibitory perisomatic synapses from PV+ basket
interneurons onto layer V pyramidal neurons. Consequently, the mPFC of Cxcl12
conditional mutants displayed attenuated inhibitory postsynaptic currents onto
layer V pyramidal neurons. Thus, postnatal CXCL12 signaling promotes a specific
interneuron circuit that inhibits mPFC activity.
PMID- 27497285
TI - Componential Network for the Recognition of Tool-Associated Actions: Evidence
from Voxel-based Lesion-Symptom Mapping in Acute Stroke Patients.
AB - The study aimed to elucidate areas involved in recognizing tool-associated
actions, and to characterize the relationship between recognition and active
performance of tool use.We performed voxel-based lesion-symptom mapping in a
prospective cohort of 98 acute left-hemisphere ischemic stroke patients (68 male,
age mean +/- standard deviation, 65 +/- 13 years; examination 4.4 +/- 2 days post
stroke). In a video-based test, patients distinguished correct tool-related
actions from actions with spatio-temporal (incorrect grip, kinematics, or tool
orientation) or conceptual errors (incorrect tool-recipient matching, e.g.,
spreading jam on toast with a paintbrush). Moreover, spatio-temporal and
conceptual errors were determined during actual tool use.Deficient spatio
temporal error discrimination followed lesions within a dorsal network in which
the inferior parietal lobule (IPL) and the lateral temporal cortex (sLTC) were
specifically relevant for assessing functional hand postures and kinematics,
respectively. Conversely, impaired recognition of conceptual errors resulted from
damage to ventral stream regions including anterior temporal lobe. Furthermore,
LTC and IPL lesions impacted differently on action recognition and active tool
use, respectively.In summary, recognition of tool-associated actions relies on a
componential network. Our study particularly highlights the dissociable roles of
LTC and IPL for the recognition of action kinematics and functional hand
postures, respectively.
PMID- 27497286
TI - Rice putative methyltransferase gene OsTSD2 is required for root development
involving pectin modification.
AB - Pectin synthesis and modification are vital for plant development, although the
underlying mechanisms are still not well understood. Here, we report the
functional characterization of the OsTSD2 gene, which encodes a putative
methyltransferase in rice. All three independent T-DNA insertion lines of OsTSD2
displayed dwarf phenotypes and serial alterations in different zones of the root.
These alterations included abnormal cellular adhesion and schizogenous aerenchyma
formation in the meristematic zone, inhibited root elongation in the elongation
zone, and higher lateral root density in the mature zone. Immunofluorescence
(with LM19) and Ruthenium Red staining of the roots showed that unesterified
homogalacturonan (HG) was increased in Ostsd2 mutants. Biochemical analysis of
cell wall pectin polysaccharides revealed that both the monosaccharide
composition and the uronic acid content were decreased in Ostsd2 mutants.
Increased endogenous ABA content and opposite roles performed by ABA and IAA in
regulating cellular adhesion in the Ostsd2 mutants suggested that OsTSD2 is
required for root development in rice through a pathway involving pectin
synthesis/modification. A hypothesis to explain the relationship among OsTSD2,
pectin methylesterification, and root development is proposed, based on pectin's
function in regional cell extension/division in a zone-dependent manner.
PMID- 27497287
TI - ABA is required for the accumulation of APX1 and MBF1c during a combination of
water deficit and heat stress.
AB - Abscisic acid (ABA) plays a key role in plant acclimation to abiotic stress.
Although recent studies suggested that ABA could also be important for plant
acclimation to a combination of abiotic stresses, its role in this response is
currently unknown. Here we studied the response of mutants impaired in ABA
signalling (abi1-1) and biosynthesis (aba1-1) to a combination of water deficit
and heat stress. Both mutants displayed reduced growth, biomass, and survival
when subjected to stress combination. Focusing on abi1-1, we found that although
its stomata had an impaired response to water deficit, remaining significantly
more open than wild type, its stomatal aperture was surprisingly reduced when
subjected to the stress combination. Stomatal closure during stress combination
in abi1-1 was accompanied by higher levels of H2O2 in leaves, suggesting that
H2O2 might play a role in this response. In contrast to the almost wild-type
stomatal closure phenotype of abi1-1 during stress combination, the accumulation
of ascorbate peroxidase 1 and multiprotein bridging factor 1c proteins, required
for acclimation to a combination of water deficit and heat stress, was
significantly reduced in abi1-1 Our findings reveal a key function for ABA in
regulating the accumulation of essential proteins during a combination of water
deficit and heat stress.
PMID- 27497288
TI - Investigation of fluorescence methods for rapid detection of municipal wastewater
impact on drinking water sources.
AB - Fluorescence spectroscopy as a means to detect low levels of treated wastewater
impact on two source waters was investigated using effluents from five wastewater
facilities. To identify how best to interpret the fluorescence excitation
emission matrices (EEMs) for detecting the presence of wastewater, several
feature selection and classification methods were compared. An expert supervised
regional integration approach was used based on previously identified features
which distinguish biologically processed organic matter including protein-like
fluorescence and the ratio of protein to humic-like fluorescence. Use of
nicotinamide adenine dinucleotide-like (NADH) fluorescence was found to result in
higher linear correlations for low levels of wastewater presence. Parallel
factors analysis (PARAFAC) was also applied to contrast an unsupervised multiway
approach to identify underlying fluorescing components. A humic-like component
attributed to reduced semiquinone-like structures was found to best correlate
with wastewater presence. These fluorescent features were used to classify, by
volume, low (0.1-0.5%), medium (1-2%), and high (5-15%) levels by applying
support vector machines (SVMs) and logistic regression. The ability of SVMs to
utilize high-dimensional input data without prior feature selection was
demonstrated through their performance when considering full unprocessed EEMs
(66.7% accuracy). The observed high classification accuracies are encouraging
when considering implementation of fluorescence spectroscopy as a water quality
monitoring tool. Furthermore, the use of SVMs for classification of fluorescence
data presents itself as a promising novel approach by directly utilizing the high
dimensional EEMs.
PMID- 27497289
TI - A combined spectroscopic and TDDFT study of natural dyes extracted from fruit
peels of Citrus reticulata and Musa acuminata for dye-sensitized solar cells.
AB - This study reports the novel spectroscopic investigations and enhanced the
electron transfers of Citrus reticulata and Musa acuminata fruit peels as the
photosensitizers for the dye-sensitized solar cells. The calculated TD-DFT
UB3LYP/6-31+G(d,p)-IEFPCM(UAKS), experiment spectra of ultra-violet-visible
spectroscopy, and Fourier transform infrared spectroscopy studies indicate the
main flavonoid (hesperidin and gallocatechin) structures of the dye extracts. The
optimized flavonoid structures are calculated using Density functional theory
(DFT) at 6-31+G(d,p) level. The rutinosyl group of the hesperidin pigment (Citrus
reticulata) will be further investigated compared to the gallocatechin (Musa
acuminata) pigment. The acidity of the dye extract is treated by adding 2% acetic
acid. The energy levels of the HOMO-LUMO dyes are measured by a combined Tauc
plot and cyclic voltammetry contrasted with the DFT data. The electrochemical
impedance spectroscopy will be performed to model the dye electron transfer. As
for the rutinosyl group presence and the acidic treatment, the acidified Citrus
reticulata cell under continuous light exposure of 100mW.cm-2 yields a short
circuit current density (Jsc) of 3.23mA/cm2, a photovoltage (Voc) of 0.48V, and a
fill factor of 0.45 corresponding to an energy conversion efficiency (eta) of
0.71% because the shifting down HOMO-LUMO edges and the broadening dye's
absorbance evaluated by a combined spectroscopic and TD-DFT method. The result
also leads to the longest diffusion length of 32.2MUm, the fastest electron
transit of 0.22ms, and the longest electron lifetime of 4.29ms.
PMID- 27497290
TI - Exploring the determinants of sanitation success in Sub-Saharan Africa.
AB - Sub-Saharan Africa (SSA) missed the Millennium Development Goal (MDG) sanitation
target by a wide margin. However, there are a few African countries which made
remarkable progress towards achieving the sanitation target. While the general
factors that influence sanitation success are widely known, some of the few
studies that have investigated the SSA sanitation situation have arrived at
different conclusions regarding the determinants of sanitation success. The
objectives of this paper were to establish the key determinants of sanitation
success in SSA countries and to classify the SSA countries based on factors
associated with sanitation success. This was achieved by analysing data drawn
from 46 SSA countries. An objective methodological approach, using regression and
cluster analyses to reveal the underlying sanitation success factors, has been
adopted. A total of 11 economic and socio-political independent variables were
tested against the dependent variable; proportion of the 2015 population that has
gained access to sanitation since 2000. Regression results showed consistent and
robust association between sanitation success and education for the national,
rural and socio-political samples (p values 0.018-0.038). These results suggest
that the level of education contributed to sanitation success in SSA during the
MDG period. For the urban sample, a negative association was demonstrated between
sanitation success and access to improved water sources (p = 0.034). This implies
that countries which made huge sanitation gains had low coverage of improved
water sources. The results from cluster analysis showed that countries which
achieved great sanitation success were characterized by the highest education
levels, incomes, population densities, political stability and high proportions
of urban population. The knowledge of the key determinants of sanitation success
could help in the formulation and design of appropriate policies and
interventions to improve sustainable sanitation access in the post-2015
development agenda.
PMID- 27497291
TI - Characteristics of psychiatric hospitalizations with multiple mechanical
restraint episodes versus hospitalization with a single mechanical restraint
episode.
AB - We investigated the characteristics of multiple episodes of mechanical restraint
versus a single episode in a psychiatric ward of a public general hospital. The
following characteristics were associated with multiple restraints: young age,
length of hospital stay, not being readmitted within 30 days from previous
discharge, and admission in the previous year before the implementation of an
intervention program to reduce mechanical restraint. The study suggests that both
organizational factors and patients' disturbed behaviour are associated with the
risk of being mechanically restrained several times.
PMID- 27497292
TI - An investigation of habit learning in Anorexia Nervosa.
AB - Anorexia Nervosa (AN) is a disorder characterised by compulsive behaviour, such
as self-starvation and excessive exercise, which develop in the pursuit of weight
loss. Recent theory suggests that once established, compulsive weight-loss
behaviours in AN may become habitual. In two parallel studies, we measured
whether individuals with AN showed a bias toward habits using two outcome
devaluation tasks. In Study 1, 23 women with AN (restrictive and binge/purge
subtypes), and 18 healthy controls (HC) completed the slips-of-action paradigm,
designed to assess reward-based habits. In Study 2, 13 women with restrictive AN,
14 women recovered from restrictive AN, and 17 female HC participants completed
the slips-of-action paradigm, and an avoidance paradigm, designed to assess
aversive habits. AN participants showed no deficit relative to HCs in the ability
to use feedback to respond correctly to stimuli. Following devaluation of
outcomes, all groups in both studies were equally able to withhold inappropriate
responses, suggesting no deficit in the balance between goal-directed and
habitual control of behaviour in these tasks in AN. These results suggest that
individuals with AN do not show a generalised tendency to rely on habits in two
outcome-devaluation tasks. Future research is needed to investigate the potential
role of disorder-specific habits in the maintenance of behaviour in AN.
PMID- 27497293
TI - Impact of psychotic symptoms on cognitive functioning in child and adolescent
psychiatric inpatients with severe mood disorders.
AB - Despite established differences in cognitive functioning of adults with mood
disorder-related psychosis and those with non-affective psychotic disorders,
there is limited evidence of the impact of psychotic symptoms on the cognitive
functioning of children and adolescents with mood disorders. This study
investigates IQ, working memory, and processing speed scores in 80 child and
adolescent inpatients discharged from an intermediate care state psychiatric
hospital, using a retrospective chart review. Associations between diagnosis
based on DSM-IV criteria (7 with Major Depression- MDD; 43 with Bipolar Disorders
BD, and 30 with Mood Disorders Not Otherwise Specified-NOS), presence of current
psychotic features, and cognitive functioning (WISC-IV IQ, Coding, Symbol Search,
and Digit Span) were investigated using Multivariate Analyses of Variance. No
differences were found in cognitive functioning between patients with MDD and BD,
or between those with severe Mood Disorders (MDD or BD) and those with NOS, when
controlling for age, gender, and presence of psychotic features. However,
patients with severe mood disorders and psychotic features showed lower IQs and
greater working memory deficits than those without psychotic features or NOS.
Results are discussed in terms of treatment planning for children and adolescents
at risk for developing psychotic symptoms and severe mood disorders.
PMID- 27497295
TI - Erratum to 'Melatonin improves methamphetamine-induced blood brain barrier
impairment through NADPH oxidase-2 in primary rat brain microvascular endothelium
cells' [Br. Ecol. Soc. 1646 (2016) 393-401].
PMID- 27497294
TI - Newly diagnosed panic disorder and the risk of erectile dysfunction: A population
based cohort study in Taiwan.
AB - Previous studies indicated that panic disorder is correlated with erectile
dysfunction (ED). The primary aim of this study was to explore the incidence rate
of ED among panic disorder patients in an Asian country. The secondary aim was to
compare the risk of ED in panic disorder patients that were treated with
different kinds of antidepressants, and to explore the possible mechanism between
these two disorders. We identified 1393 male patients with newly diagnosed panic
disorder from the Taiwan's National Health Insurance Database. Four matched
controls per case were selected for the study group by propensity score. After
adjusting for age, obesity and comorbidities, the panic disorder patients had a
higher hazard ratio of ED diagnosis than the controls, especially among the
untreated panic disorder patients. This retrospective dynamic cohort study
supports the link between ED and prior panic disorder in a large sample of panic
disorder patients. This study points out the need of early antidepressant
treatment for panic disorder to prevent further ED.
PMID- 27497296
TI - Oncolytic herpes simplex virus interactions with the host immune system.
AB - Oncolytic viruses (OVs), like oncolytic herpes simplex virus (oHSV), are
genetically engineered to selectively replicate in and kill cancer cells, while
sparing normal cells. Initial OV infection, cell death, and subsequent OV
propagation within the tumor microenvironment leads to a cascade of host
responses (innate and adaptive), reflective of natural anti-viral immune
responses. These host-virus interactions are critical to the balance between OV
activities, anti-viral immune responses limiting OV, and induction of anti-tumor
immunity. The host response against oHSV is complex, multifaceted, and modulated
by the tumor microenvironment and immunosuppression. As a successful pathogen,
HSV has multiple mechanisms to evade such host responses. In this review, we will
discuss these mechanisms and HSV evasion, and how they impact oHSV therapy.
PMID- 27497297
TI - The plant-specific CDKB1-CYCB1 complex mediates homologous recombination repair
in Arabidopsis.
AB - Upon DNA damage, cyclin-dependent kinases (CDKs) are typically inhibited to block
cell division. In many organisms, however, it has been found that CDK activity is
required for DNA repair, especially for homology-dependent repair (HR), resulting
in the conundrum how mitotic arrest and repair can be reconciled. Here, we show
that Arabidopsis thaliana solves this dilemma by a division of labor strategy. We
identify the plant-specific B1-type CDKs (CDKB1s) and the class of B1-type
cyclins (CYCB1s) as major regulators of HR in plants. We find that RADIATION
SENSITIVE 51 (RAD51), a core mediator of HR, is a substrate of CDKB1-CYCB1
complexes. Conversely, mutants in CDKB1 and CYCB1 fail to recruit RAD51 to
damaged DNA CYCB1;1 is specifically activated after DNA damage and we show that
this activation is directly controlled by SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1),
a transcription factor that acts similarly to p53 in animals. Thus, while the
major mitotic cell-cycle activity is blocked after DNA damage, CDKB1-CYCB1
complexes are specifically activated to mediate HR.
PMID- 27497298
TI - Loss of FBXO7 (PARK15) results in reduced proteasome activity and models a
parkinsonism-like phenotype in mice.
AB - Mutations in the FBXO7 (PARK15) gene have been implicated in a juvenile form of
parkinsonism termed parkinsonian pyramidal syndrome (PPS), characterized by
Parkinsonian symptoms and pyramidal tract signs. FBXO7 (F-box protein only 7) is
a subunit of the SCF (SKP1/cullin-1/F-box protein) E3 ubiquitin ligase complex,
but its relevance and function in neurons remain to be elucidated. Here, we
report that the E3 ligase FBXO7-SCF binds to and ubiquitinates the proteasomal
subunit PSMA2. In addition, we show that FBXO7 is a proteasome-associated protein
involved in proteasome assembly. In FBXO7 knockout mice, we find reduced
proteasome activity and early-onset motor deficits together with premature death.
In addition, we demonstrate that NEX (neuronal helix-loop-helix protein-1)-Cre
induced deletion of the FBXO7 gene in forebrain neurons or the loss of FBXO7 in
tyrosine hydroxylase (TH)-positive neurons results in motor defects, reminiscent
of the phenotype in PARK15 patients. Taken together, our study establishes a
vital role for FBXO7 in neurons, which is required for proper motor control and
accentuates the importance of FBXO7 in proteasome function.
PMID- 27497300
TI - Transcriptome discovery in non-model wild fish species for the development of
quantitative transcript abundance assays.
AB - Environmental studies increasingly identify the presence of both contaminants of
emerging concern (CECs) and legacy contaminants in aquatic environments; however,
the biological effects of these compounds on resident fishes remain largely
unknown. High throughput methodologies were employed to establish partial
transcriptomes for three wild-caught, non-model fish species; smallmouth bass
(Micropterus dolomieu), white sucker (Catostomus commersonii) and brown bullhead
(Ameiurus nebulosus). Sequences from these transcriptome databases were utilized
in the development of a custom nCounter CodeSet that allowed for direct
multiplexed measurement of 50 transcript abundance endpoints in liver tissue.
Sequence information was also utilized in the development of quantitative real
time PCR (qPCR) primers. Cross-species hybridization allowed the smallmouth bass
nCounter CodeSet to be used for quantitative transcript abundance analysis of an
additional non-model species, largemouth bass (Micropterus salmoides). We
validated the nCounter analysis data system with qPCR for a subset of genes and
confirmed concordant results. Changes in transcript abundance biomarkers between
sexes and seasons were evaluated to provide baseline data on transcript
modulation for each species of interest.
PMID- 27497299
TI - NSUN3 and ABH1 modify the wobble position of mt-tRNAMet to expand codon
recognition in mitochondrial translation.
AB - Mitochondrial gene expression uses a non-universal genetic code in mammals.
Besides reading the conventional AUG codon, mitochondrial (mt-)tRNAMet mediates
incorporation of methionine on AUA and AUU codons during translation initiation
and on AUA codons during elongation. We show that the RNA methyltransferase NSUN3
localises to mitochondria and interacts with mt-tRNAMet to methylate cytosine 34
(C34) at the wobble position. NSUN3 specifically recognises the anticodon stem
loop (ASL) of the tRNA, explaining why a mutation that compromises ASL
basepairing leads to disease. We further identify ALKBH1/ABH1 as the dioxygenase
responsible for oxidising m5C34 of mt-tRNAMet to generate an f5C34 modification.
In vitro codon recognition studies with mitochondrial translation factors reveal
preferential utilisation of m5C34 mt-tRNAMet in initiation. Depletion of either
NSUN3 or ABH1 strongly affects mitochondrial translation in human cells, implying
that modifications generated by both enzymes are necessary for mt-tRNAMet
function. Together, our data reveal how modifications in mt-tRNAMet are generated
by the sequential action of NSUN3 and ABH1, allowing the single mitochondrial
tRNAMet to recognise the different codons encoding methionine.
PMID- 27497301
TI - Phosphorylation of phosphoenolpyruvate carboxykinase (PEPCK) and
phosphoenolpyruvate carboxylase (PEPC) in the flesh of fruits.
AB - This study determined whether phosphoenolpyruvate carboxykinase (PEPCK) and
phosphoenolpyruvate carboxylase (PEPC) are phosphorylated in the flesh of a range
of fruits. This was done by incubating fruit flesh with 32P[P] (where 32P[P] =
32PO43-), then PEPCK and PEPC were immunoprecipitated from extracts using
specific antisera. The incorporation of 32P[P] into these enzymes was then
determined by autoradiography of SDS-PAGE gels. Both enzymes were subject to
phosphorylation in vivo in the flesh of grape, tomato, cherry and plum. PEPCK was
also subject to phosphorylation in vivo in developing grape seeds. Proteolytic
cleavage of PEPCK showed that it was phosphorylated at a site(s) located on its N
terminal extension. Potentially phosphorylation of these enzymes could contribute
to the coordinate regulation of their activities in the flesh of fruits and in
developing seeds.
PMID- 27497302
TI - Cold stress affects H+-ATPase and phospholipase D activity in Arabidopsis.
AB - Low temperature is an environmental stress that greatly influences plant
performance and distribution. Plants exposed to cold stress exhibit modifications
of plasma membrane physical properties that can affect their functionality. Here
it is reported the effect of low temperature exposure of Arabidopsis plants on
the activity of phospholipase D and H+-ATPase, the master enzyme located at the
plasma membrane. The H+-ATPase activity was differently affected, depending on
the length of cold stress imposed. In particular, an exposure to 4 degrees C for
6 h determined the strong inhibition of the H+-ATPase activity, that correlates
with a reduced association with the regulatory 14-3-3 proteins. A longer exposure
first caused the full recovery of the enzymatic activity followed by a
significant activation, in accordance with both the increased association with 14
3-3 proteins and induction of H+-ATPase gene transcription. Different time
lengths of cold stress treatment were also shown to strongly stimulate the
phospholipase D activity and affect the phosphatidic acid levels of the plasma
membranes. Our results suggest a functional correlation between the activity of
phospholipase D and H+-ATPase mediated by phosphatidic acid release during the
cold stress response.
PMID- 27497303
TI - Effects of dietary 2,2', 4,4'-tetrabromodiphenyl ether (BDE-47) exposure in
growing medaka fish (Oryzias latipes).
AB - In this research work, we addressed the effects of a diet fortified with BDE-47
(0, 10, 100, 1000ng/g) dosed to 4-7 day-old post-hatch medaka fish for 40 days,
followed by an 80-day depuration period. BDE-47 accumulation and overall growth
were evaluated throughout the dosing period, and its elimination was quantified
over the following 60 days. The histological condition of the thyroid gland,
liver and gonads from the 1000ng BDE-47-treated fish were assessed 5 and 70days
after exposures finished. The phenotypic males to females ratio was also
quantified 70days after treatments finished. Sixty days after the BDE-47
exposures, reproductive capacity (i.e. fecundity, fertility and hatchability) was
evaluated in mating groups for a 20-day period. BDE-47 exposure via food from
larval through juvenile life stages of medaka fish resulted in steady
accumulation with time dose-dependently. This accumulation tendency rapidly
decreased after dosing ended. The growth rates showed a significant increase only
at the highest concentration 70days after exposures finished. The histological
survey did not reveal BDE-47-related alterations in the condition of the
potential target organs. However, a morphometrical approach suggested BDE-47
related differences in the thickness of the epithelium that lines thyroid
follicles. The reproduction studies showed comparable values for the fecundity,
fertility and hatching rates. Dietary BDE-47 dosed for 40days to growing medaka
fish did not alter the phenotypic sex ratios at maturity. The dietary approach
used herein could not provide conclusive evidence of effects on medaka
development and thriving despite the fact that BDE-47 underwent rapid
accumulation in whole fish during the 40-day treatment.
PMID- 27497305
TI - Analytical characteristics and application of novel chitosan coated magnetic
nanoparticles as an efficient drug delivery system for ciprofloxacin. Enhanced
drug release kinetics by low-frequency ultrasounds.
AB - A pH-responsive drug carrier based on chitosan coated iron oxide nanoparticles
(CS-Fe3O4) for prolonged antibiotic release in a controlled manner is reported.
As an antibiotic drug model, ciprofloxacin was loaded onto the nanocarrier via H
bonding interactions. The nanoparticles were characterized using scanning
electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy,
photon correlation spectroscopy and Fourier transform infrared spectroscopy. The
particle size of CS-Fe3O4 nanoparticles were found to lie in the range of 30
80nm. The analytical characteristics of the designed system were thoroughly
investigated. The in vitro drug loading at pH 4.8 and release kinetics at pH 7.4
studies revealed that the drug delivery system can take 99% of ciprofloxacin load
and quantitatively release the drug over a sustained period of 5 days. The
release kinetics study indicated that the system follows a zero order kinetics
via a diffusion-controlled mechanism. These results indicated that CS-Fe3O4
nanoparticles have the potential for use as controlled antibiotic delivery
systems through oral administration by avoiding the drug release in the highly
acidic gastric fluid region of the stomach. Furthermore, the ability of low
frequency ultrasound in fast release of the encapsulated drug in less than 60min
from the CS-Fe3O4 nanoparticles in a controlled manner was confirmed.
PMID- 27497304
TI - Gene expression in Catla catla (Hamilton) subjected to acute and protracted doses
of gamma radiation.
AB - Studies on transcriptional modulation after gamma radiation exposure in fish are
limited. Cell cycle perturbations and expression of apoptotic genes were
investigated in the fish, Catla catla after acute and protracted exposures to
gamma radiation over a 90day period. Significant changes in gene expression were
observed between day 1 and 90 post-exposure. Gamma radiation induced a
significant down-regulation of target genes gadd45alpha, cdk1 and bcl-2 from day
1 to day 3 after protracted exposure, whereas it persists till day 6 upon acute
exposure. From day 12 onwards, Gadd45alpha, cdk1 and bcl-2 genes were up
regulated following protracted exposure, indicating DNA repair, cell-cycle arrest
and apoptosis. There exists a linear correlation between these genes (gadd45alpha
- r=0.85, p=0.0073; cdk1 - r=0.86, p=0.0053; bcl-2 - r=0.89, p=0.0026) at
protracted exposures. This is the first report on the dual role of bcl-2 gene in
fish exposed to acute and protracted radiation and correlation among the
aforementioned genes that work in concert to promote 'repair' and 'death'
circuitries in fish blood cells.
PMID- 27497306
TI - A study of the influence on diabetes of free and conjugated bisphenol A
concentrations in urine: Development of a simple microextraction procedure using
gas chromatography-mass spectrometry.
AB - The association between bisphenol A (BPA) exposure and adult health status is
examined by measuring the urinary BPA concentration using a miniaturized
technique based on dispersive liquid-liquid microextraction (DLLME) in
combination with gas chromatography-mass spectrometry (GC-MS). Both the free
bioactive and the glucuronide conjugated forms of BPA were measured, the
glucuronide form usually being predominant. The main analogs of BPA, including
bisphenol Z (BPZ), bisphenol F (BPF) and biphenol (BP) were also determined.
Several parameters affecting enzymatic hydrolysis, derivatization by in-situ
acetylation and the DLLME stages were carefully optimized by means of
multivariate designs. DLLME parameters were 2mL urine, 1mL acetone and 100MUL
chloroform, and hydrolysis was performed using beta-glucuronidase and sulfatase
at pH 5. No matrix effect was observed and quantification was carried out by
aqueous calibration with a surrogate standard. Detection limits were in the range
0.01-0.04ngmL(-1). The intraday and interday precisions were lower than 11% in
terms of relative standard deviation. Satisfactory values for all compounds were
obtained in recovery studies (92-117%) at two concentration levels. Other
bisphenols (BPF, BPZ and BP) were not detected in the urine samples, while BPA
was the only bisphenol detected in the free form (creatinine adjusted) at
concentration levels ranging from the detection limit to 15.9ngg(-1), and total
BPA was detected at concentrations ranging from 0.46 to 24.5ngg(-1) levels. A
comparison of the BPA content for both groups of patients revealed that slightly
higher mean values were obtained for both free BPA and total BPA for diabetic
patients, than for non-diabetic patients. However, a statistical comparison of
the contents of BPA revealed that there were no significant differences. The
procedure was validated using a certified reference material.
PMID- 27497307
TI - Isolation and chatacterization of homoisoflavonoids from Dracaena cochinchinensis
and their osteogenic activities in mouse mesenchymal stem cells.
AB - Two new homoisoflavonoids, dracaeconolide A (1) and dracaeconolide B (2),
together with ten known compounds, namely (3R)-7,4'-dihydroxy-8
methoxyhomoisoflavane (3), (3R)-7-hydroxy-3-(4-hydroxybenzyl)chromane (4), (3R)
7,4'-dihydroxy-5-methoxy-homoisoflavane (5), (3R)-6,4'-dihydroxy-8
methoxyhomoisoflavan (6), 7,4'-dihydroxy-8-methylflavan (7), (2R)-7,4'-dihydroxy
5-methoxy-8-methylflavan (8), 5,4'-dihydroxy-7-methoxy-6-methylflavane (9), 7,4'
dihydroxy-3'-methoxyflavan (10), 7,4'-dihydroxyflavan (11), 4,4'-dihydroxy-2,6
dimethoxydihydrochlcone (12), were isolated from the red resin of Dracaena
cochinchinensis (dragon's blood, DB). All the compounds were then evaluated for
their effects on mouse bone marrow-derived mesenchymal stem cells (MSCs)
proliferation using CCK8 assay and their abilities in promoting MSCs
differentiating into osteoblast through the assay of alkaline phosphatase (ALP)
activity in vitro. Compounds 2, 3, 4, 7, 9, and 11, at a concentration of 10MUM
with no cytotoxicity, significantly promoted MSC osteogenic differentiation by
increasing the levels of ALP activity to percents of 159.6+/-5.9, 167.6+/-10.9,
162.0+/-1.4, 151.3+/-4.0, 171.0+/-8.2, and 169.9+/-7.3 in relative to the
control, respectively. The results of ALP staining were in accordance to that of
ALP activity.
PMID- 27497308
TI - End-of-life management of corrosive drywall.
AB - Recently, gypsum drywall products imported to the United States (US) were found
to cause metal corrosion and tarnishing in some homes, often necessitating that
this drywall be discarded. Research assessed the potential implications of
recycling and landfilling corrosive/imported drywall. Samples of corrosive
drywall were collected from homes in Florida, US and these characteristics were
assessed relative to domestically-produced drywall purchased from retail outlets.
The total and synthetic precipitation leaching procedure (SPLP) leachable heavy
metal concentrations were measured and compared to risk-based regulatory
thresholds to assess the possible land application risk. In a majority of
samples, concentrations were below levels of regulatory concern. The mean
concentration of several elements exceeded the thresholds in a few samples for
the direct exposure assessment (As) and the groundwater leaching assessment (Al,
B, Hg, Mn, Sr and V); but the results did not suggest that corrosive drywall
would present a greater risk than domestic drywall. To assess landfilling
concerns, the potential for sulfur gases emissions upon disposal was evaluated.
Experiments indicated that corrosive drywall would not pose a greater risk of
long-term H2S emissions compared to domestic drywall.
PMID- 27497309
TI - Synthesis of a water-soluble thiourea-formaldehyde (WTF) resin and its
application to immobilize the heavy metal in MSWI fly ash.
AB - Because of the high concentrations of heavy metals, municipal solid waste
incineration (MSWI) fly ash is classified as a hazardous waste, which need to be
treated to avoid damaging the environment. A novel water-soluble thiourea
formaldehyde (WTF) resin was synthesized by two step reactions
(hydroxymethylation reaction and condensation reaction) in the laboratory.
Synthetic conditions, removal of free formaldehyde in the resin and the ability
of immobilization heavy metals in the MSWI fly ash were studied. The possible
molecular structure of the resin was also discussed by elemental analysis and
FTIR spectra. Experimental results showed that the synthesis conditions of WTF
resin were the formaldehyde/thiourea (T/F) mole ratio of 2.5:1,
hydroxymethylation at pH 7.0-8.0 and 60 degrees C for 30min, and condensation of
at pH 4.5-5.0 and 80 degrees C. In addition, the end point of condensation
reaction was measured by turbidity point method. The result of elemental analysis
and FTIR spectra indicated that thiourea functional group in the WTF resin
chelated the heavy metal ions. Melamine can efficiently reduce the free
formaldehyde content in the resin from 8.5% to 2%. The leaching test showed that
the immobilization rates of Cr, Pb and Cd were 96.5%, 92.0% and 85.8%,
respectively. Leaching concentrations of Cr, Pb and Cd in the treated fly ash
were decreased to 0.08 mg/L, 2.44 mg/L and 0.23 mg/L, respectively. The MSWI fly
ash treated by WTF resin has no harm to the environment.
PMID- 27497310
TI - Pseudomonas-related populations associated with reverse osmosis in drinking water
treatment.
AB - Reverse osmosis membrane filtration technology (RO) is used to treat drinking
water. After RO treatment, bacterial growth is still observed in water. However,
it is not clear whether those microorganisms belong to species that can pose a
health risk, such as Pseudomonas spp. The goal of this study is to characterize
the bacterial isolates from a medium that is selective for Pseudomonas and
Aeromonas which were present in the water fraction before and after the RO. To
this end, isolates were recovered over two years and were identified by matrix
assisted laser desorption/ionization-time of flight mass spectrometry. They were
then biochemically phenotyped and the population similarity indexes were
calculated. The isolates were analysed for their capacity to form biofilms in
vitro and antimicrobial susceptibility. There were significant differences
between the microbial populations in water before and after RO. Furthermore, the
structures of the populations analysed at the same sampling point were similar in
different sampling campaigns. Some of the isolates had the capacity to form a
biofilm and showed resistance to different antibiotics. A successful level
filtration via RO and subsequent recolonization of the membrane with different
species from those in the feed water was found. Pseudomonas aeruginosa was not
recovered from among the isolates. This study increases the knowledge on the
microorganisms present in water after RO treatment, with focus in one of the
genus causing problems in RO systems associated with human health risk,
Pseudomonas.
PMID- 27497311
TI - Selective coal mine overburden treatment with topsoil and compost to optimise
pasture or native vegetation establishment.
AB - Overburden at a coal mine in the Hunter Valley, New South Wales, was stored in a
flat-topped artificial mound with 14-degree side slopes. Topsoil was scarce,
dispersive and readily eroded. A split-plot factorial experiment applied an
enhanced municipal solid waste compost at 0, 60 or 100 t ha(-1) to untreated
overburden or to overburden covered with 0.1 m of topsoil. Two seeding
treatments, of trees and shrubs or of pasture species, were applied to two 0.5-ha
replicates of each surface treatment. Substrate physical and chemical properties
and vegetation attributes were assessed 2.5 years later. Compost application to
both topsoil and overburden significantly increased total N, P, Cu and Zn,
soluble K, Ca and Mg, and significantly reduced soluble Na and pH. Mean tree
density, size and total canopy cover were significantly greater with compost
applied at 60 t ha(-1) to overburden than with all other treatments, especially
those on topsoil where tree growth was inhibited by undesired species. Compost
application to overburden and topsoil at 100 t ha(-1) significantly increased
biomass of desired pasture species and significantly reduced undesired species
cover compared with unamended topsoil and the extent of bare ground compared with
unamended overburden. Successful development of woody species on overburden and
pastures on both overburden and topsoil treated with compost provides
opportunities for new combinations of landscape design, surface preparation and
plant species introductions to increase the stability of final landforms, the
effectiveness of resource use, and the delivery of commercial and biodiversity
benefits from mine site rehabilitation.
PMID- 27497313
TI - Corrigendum to "Clinical and biochemical indicators of homeostasis model
assessment estimated insulin resistance in postmenopausal women" [J Chin Med
Assoc 74 (2011) 442-447].
PMID- 27497312
TI - A critical review on textile wastewater treatments: Possible approaches.
AB - Waste water is a major environmental impediment for the growth of the textile
industry besides the other minor issues like solid waste and resource waste
management. Textile industry uses many kinds of synthetic dyes and discharge
large amounts of highly colored wastewater as the uptake of these dyes by fabrics
is very poor. This highly colored textile wastewater severely affects
photosynthetic function in plant. It also has an impact on aquatic life due to
low light penetration and oxygen consumption. It may also be lethal to certain
forms of marine life due to the occurrence of component metals and chlorine
present in the synthetic dyes. So, this textile wastewater must be treated before
their discharge. In this article, different treatment methods to treat the
textile wastewater have been presented along with cost per unit volume of treated
water. Treatment methods discussed in this paper involve oxidation methods
(cavitation, photocatalytic oxidation, ozone, H2O2, fentons process), physical
methods (adsorption and filtration), biological methods (fungi, algae, bacteria,
microbial fuel cell). This review article will also recommend the possible
remedial measures to treat different types of effluent generated from each
textile operation.
PMID- 27497315
TI - Did Viruses Evolve As a Distinct Supergroup from Common Ancestors of Cells?
AB - The evolutionary origins of viruses according to marker gene phylogenies, as well
as their relationships to the ancestors of host cells remains unclear. In a
recent article Nasir and Caetano-Anolles reported that their genome-scale
phylogenetic analyses based on genomic composition of protein structural-domains
identify an ancient origin of the "viral supergroup" (Nasir et al. 2015. A
phylogenomic data-driven exploration of viral origins and evolution. Sci Adv.
1(8):e1500527.). It suggests that viruses and host cells evolved independently
from a universal common ancestor. Examination of their data and phylogenetic
methods indicates that systematic errors likely affected the results. Reanalysis
of the data with additional tests shows that small-genome attraction artifacts
distort their phylogenomic analyses, particularly the location of the root of the
phylogenetic tree of life that is central to their conclusions. These new results
indicate that their suggestion of a distinct ancestry of the viral supergroup is
not well supported by the evidence.
PMID- 27497314
TI - Variation in the oxytocin receptor gene (OXTR) is associated with differences in
moral judgment.
AB - Moral judgments are produced through the coordinated interaction of multiple
neural systems, each of which relies on a characteristic set of
neurotransmitters. Genes that produce or regulate these neurotransmitters may
have distinctive influences on moral judgment. Two studies examined potential
genetic influences on moral judgment using dilemmas that reliably elicit
competing automatic and controlled responses, generated by dissociable neural
systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate
genes and identified a nominal association between a polymorphism (rs237889) of
the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian
moral judgment (that is, judgments favoring individual rights vs the greater
good). An association was likewise observed for rs1042615 of the arginine
vasopressin receptor gene (AVPR1A). Study 2 (N = 322) aimed to replicate these
findings using the aforementioned dilemmas as well as a new set of structurally
similar medical dilemmas. Study 2 failed to replicate the association with
AVPR1A, but replicated the OXTR finding using both the original and new dilemmas.
Together, these findings suggest that moral judgment is influenced by variation
in the oxytocin receptor gene and, more generally, that single genetic
polymorphisms can have a detectable effect on complex decision processes.
PMID- 27497316
TI - The Molecular Chaperone DnaK Is a Source of Mutational Robustness.
AB - Molecular chaperones, also known as heat-shock proteins, refold misfolded
proteins and help other proteins reach their native conformation. Thanks to these
abilities, some chaperones, such as the Hsp90 protein or the chaperonin GroEL,
can buffer the deleterious phenotypic effects of mutations that alter protein
structure and function. Hsp70 chaperones use a chaperoning mechanism different
from that of Hsp90 and GroEL, and it is not known whether they can also buffer
mutations. Here, we show that they can. To this end, we performed a mutation
accumulation experiment in Escherichia coli, followed by whole-genome
resequencing. Overexpression of the Hsp70 chaperone DnaK helps cells cope with
mutational load and completely avoid the extinctions we observe in lineages
evolving without chaperone overproduction. Additionally, our sequence data show
that DnaK overexpression increases mutational robustness, the tolerance of its
clients to nonsynonymous nucleotide substitutions. We also show that this
elevated mutational buffering translates into differences in evolutionary rates
on intermediate and long evolutionary time scales. Specifically, we studied the
evolutionary rates of DnaK clients using the genomes of E. coli, Salmonella
enterica, and 83 other gamma-proteobacteria. We find that clients that interact
strongly with DnaK evolve faster than weakly interacting clients. Our results
imply that all three major chaperone classes can buffer mutations and affect
protein evolution. They illustrate how an individual protein like a chaperone can
have a disproportionate effect on the evolution of a proteome.
PMID- 27497317
TI - Centromeres of the Yeast Komagataella phaffii (Pichia pastoris) Have a Simple
Inverted-Repeat Structure.
AB - Centromere organization has evolved dramatically in one clade of fungi, the
Saccharomycotina. These yeasts have lost the ability to make normal eukaryotic
heterochromatin with histone H3K9 methylation, which is a major component of
pericentromeric regions in other eukaryotes. Following this loss, several
different types of centromere emerged, including two types of sequence-defined
("point") centromeres, and the epigenetically defined "small regional"
centromeres of Candida albicans Here we report that centromeres of the
methylotrophic yeast Komagataella phaffii (formerly called Pichia pastoris) are
structurally defined. Each of its four centromeres consists of a 2-kb inverted
repeat (IR) flanking a 1-kb central core (mid) region. The four centromeres are
unrelated in sequence. CenH3 (Cse4) binds strongly to the cores, with a
decreasing gradient along the IRs. This mode of organization resembles
Schizosaccharomyces pombe centromeres but is much more compact and lacks the
extensive flanking heterochromatic otr repeats. Different isolates of K. phaffii
show polymorphism for the orientation of the mid regions, due to recombination in
the IRs. CEN4 is located within a 138-kb region that changes orientation during
mating-type switching, but switching does not induce recombination of centromeric
IRs. Our results demonstrate that evolutionary transitions in centromere
organization have occurred in multiple yeast clades.
PMID- 27497318
TI - Evolved Populations of Shigella flexneri Phage Sf6 Acquire Large Deletions,
Altered Genomic Architecture, and Faster Life Cycles.
AB - Genomic architecture is the framework within which genes and regulatory elements
evolve and where specific constructs may constrain or potentiate particular
adaptations. One such construct is evident in phages that use a headful packaging
strategy that results in progeny phage heads packaged with DNA until full rather
than encapsidating a simple unit-length genome. Here, we investigate the
evolution of the headful packaging phage Sf6 in response to barriers that impede
efficient phage adsorption to the host cell. Ten replicate populations evolved
faster Sf6 life cycles by parallel mutations found in a phage lysis gene and/or
by large, 1.2- to 4.0-kb deletions that remove a mobile genetic IS911 element
present in the ancestral phage genome. The fastest life cycles were found in
phages that acquired both mutations. No mutations were found in genes encoding
phage structural proteins, which were a priori expected from the experimental
design that imposed a challenge for phage adsorption by using a Shigella flexneri
host lacking receptors preferred by Sf6. We used DNA sequencing, molecular
approaches, and physiological experiments on 82 clonal isolates taken from all 10
populations to reveal the genetic basis of the faster Sf6 life cycle. The
majority of our isolates acquired deletions in the phage genome. Our results
suggest that deletions are adaptive and can influence the duration of the phage
life cycle while acting in conjunction with other lysis time-determining point
mutations.
PMID- 27497319
TI - Trends in Medicalization of Children with Amplified Musculoskeletal Pain
Syndrome.
AB - Objective: The objective of this survey was to describe trends over time in
medicalization of children with Amplified Musculoskeletal Pain Syndrome (AMPS).
Design: A retrospective evaluation was conducted using self-reported data from
patients presenting to the pain clinic between January 1, 2008 and December 31,
2014, who were diagnosed with AMPS. Setting and Subjects: This was a medical
record review of 899 subjects ages 3-20 presenting with Amplified Musculoskeletal
Pain Syndrome. Subjects were included if they presented to a single tertiary
specialized clinic and obtained a diagnosis of AMPS between January 1, 2008 and
December 31, 2014. Methods: Information collected from subjects' medical records
included: past medications, current outpatient medications, procedures, aids,
therapies, studies, professionals seen, hospitalizations, and surgeries. Trends
in medicalization were analyzed by year of initial visit. Results: Medication
use, procedures, studies, therapies, professionals seen, hospitalizations, and
surgeries in children with AMPS all increased significantly by year ( P <
0.001). The degree of physical dysfunction, pain, and the use of aids did not
significantly increase. Conclusions: Children with amplified musculoskeletal pain
syndrome are becoming increasingly medicalized. Increased medicalization
introduces risk of iatrogenic injury and burdens families with unnecessary
medical costs. The significant increase in medicalization of children with AMPS
is not related to an increase in patient reported pain, which is evidenced by the
lack of significant increase in patients' pain score, pain duration, or
functional disability at the time of their initial evaluation.
PMID- 27497321
TI - Characterization of Macrophage/Microglial Activation and Effect of
Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain.
AB - Objective: Neuropathic pain is common and debilitating with limited effective
treatments. Macrophage/microglial activation along ascending somatosensory
pathways following peripheral nerve injury facilitates neuropathic pain. However,
polarization of macrophages/microglia in neuropathic pain is not well understood.
Photobiomodulation treatment has been used to decrease neuropathic pain, has anti
inflammatory effects in spinal injury and wound healing models, and modulates
microglial polarization in vitro. Our aim was to characterize
macrophage/microglia response after peripheral nerve injury and modulate the
response with photobiomodulation. Methods: Adult male Sprague-Dawley rats were
randomly assigned to sham (N = 13), spared nerve injury (N = 13), or injury +
photobiomodulation treatment groups (N = 7). Mechanical hypersensitivity was
assessed with electronic von Frey. Photobiomodulation (980 nm) was applied to
affected hind paw (output power 1 W, 20 s, 41cm above skin, power density 43.25
mW/cm 2 , dose 20 J), dorsal root ganglia (output power 4.5W, 19s, in skin
contact, power density 43.25 mW/cm 2 , dose 85.5 J), and spinal cord regions
(output power 1.5 W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose
28.5 J) every other day from day 7-30 post-operatively. Immunohistochemistry
characterized macrophage/microglial activation. Results: Injured groups
demonstrated mechanical hypersensitivity 1-30 days post-operatively.
Photobiomodulation-treated animals began to recover after two treatments; at day
26, mechanical sensitivity reached baseline. Peripheral nerve injury caused
region-specific macrophages/microglia activation along spinothalamic and dorsal
column medial lemniscus pathways. A pro-inflammatory microglial marker was
expressed in the spinal cord of injured rats compared to photobiomodulation
treated and sham group. Photobiomodulation-treated dorsal root ganglion
macrophages expressed anti-inflammatory markers. Conclusion: Photobiomodulation
effectively reduced mechanical hypersensitivity, potentially through modulating
macrophage/microglial activation to an anti-inflammatory phenotype.
PMID- 27497322
TI - Pain Increases the Risk of Developing Frailty in Older Adults with
Osteoarthritis.
AB - Objective: While osteoarthritis (OA)-related pain increases the risk of physical
inactivity, disability, and falls, less is known about whether pain increases the
risk of frailty. We investigated if people with OA reporting pain are more likely
to develop frailty than people with OA without pain. Design: Population-based
prospective cohort study with a follow-up of 4.4 years. Setting: Community.
Subjects: The subjects were 1,775 older men and women with osteoarthritis,
enrolled in the Progetto Veneto Anziani. Methods: Pain was ascertained according
to medical records, symptoms/signs, and use of analgesics. Participants were
considered frail if they met three out of five criteria of Fried's Index.
Results: Cross-sectional analysis at baseline demonstrated that after adjusting
for potential confounders (age, gender, anthropometric and demographic data,
comorbidities), people with OA and pain (n = 568) were significantly more likely
to have frailty compared with those with OA without pain (n = 1,207; hand OA, OR
= 1.86, 95% CI = 1.65-2.09; hip OA, OR = 1.62, 95% CI = 1.44-1.83; knee OA, OR =
1.42, 95% CI = 1.26-1.60; all p < 0.0001). Prospective analysis of 1,152
nonfrail subjects at baseline demonstrated that 19.9% developed incident frailty.
A fully-adjusted logistic regression analysis demonstrated that lower limb OA
related pain was associated with an increased risk of developing frailty compared
with people with OA and no pain. Conclusions: Pain related to OA might be an
important factor influencing the relationship between OA and the development of
frailty.
PMID- 27497320
TI - HIV Distal Neuropathic Pain Is Associated with Smaller Ventral Posterior
Cingulate Cortex.
AB - Objective: . Despite modern antiretroviral therapy, HIV-associated neuropathy is
one of the most prevalent, disabling and treatment-resistant complications of HIV
disease. The presence and intensity of distal neuropathic pain is not fully
explained by the degree of peripheral nerve damage. A better understanding of
brain structure in HIV distal neuropathic pain may help explain why some patients
with HIV neuropathy report pain while the majority does not. Previously, we
reported that more intense distal neuropathic pain was associated with smaller
total cerebral cortical gray matter volumes. The objective of this study was to
determine which parts of the cortex are smaller. Methods: . HIV positive
individuals with and without distal neuropathic pain enrolled in the multisite (N
= 233) CNS HIV Antiretroviral Treatment Effects (CHARTER) study underwent
structural brain magnetic resonance imaging. Voxel-based morphometry was used to
investigate regional brain volumes in these structural brain images. Results: .
Left ventral posterior cingulate cortex was smaller for HIV positive individuals
with versus without distal neuropathic pain (peak P = 0.017; peak t = 5.15; MNI
coordinates x = -6, y = -54, z = 20). Regional brain volumes within cortical gray
matter structures typically associated with pain processing were also smaller for
HIV positive individuals having higher intensity ratings of distal neuropathic
pain. Conclusions: . The posterior cingulate is thought to be involved in
inhibiting the perception of painful stimuli. Mechanistically a smaller posterior
cingulate cortex structure may be related to reduced anti-nociception
contributing to increased distal neuropathic pain.
PMID- 27497324
TI - High-Molecular-Weight Paired Helical Filaments from Alzheimer Brain Induces
Seeding of Wild-Type Mouse Tau into an Argyrophilic 4R Tau Pathology in Vivo.
AB - In Alzheimer disease, the development of tau pathology follows neuroanatomically
connected pathways, suggesting that abnormal tau species might recruit normal tau
by passage from cell to cell. Herein, we analyzed the effect of stereotaxic brain
injection of human Alzheimer high-molecular-weight paired helical filaments
(PHFs) in the dentate gyrus of wild-type and mutant tau THY-Tau22 mice. After 3
months of incubation, wild-type and THY-Tau22 mice developed an atrophy of the
dentate gyrus and a tau pathology characterized by Gallyas and tau-positive grain
like inclusions into granule cells that extended in the hippocampal hilus and
eventually away into the alveus, and the fimbria. Gallyas-positive neuropil
threads and oligodendroglial coiled bodies were also observed. These tau
inclusions were composed only of mouse tau, and were immunoreactive with
antibodies to 4R tau, phosphotau, misfolded tau, ubiquitin, and p62. Although
local hyperphosphorylation of tau was increased in the dentate gyrus in THY-Tau22
mice, the development of neurofibrillary tangles made of mutant human tau was not
accelerated in the hippocampus, indicating that wild-type human PHFs were
inefficient in seeding tau aggregates made of G272V/P301S mutant human tau. Our
results indicate thus that injection of human wild-type Alzheimer PHF seeded
aggregation of wild-type murine tau into an argyrophilic 4R tau pathology, and
constitutes an interesting model independent of expression of a mutant tau
protein.
PMID- 27497325
TI - Genotyping of the c.1423C>T (p.P475S) polymorphism in the ADAMTS13 gene by APLP
and HRM assays: Northeastern Asian origin of the mutant.
AB - ADAMTS13 is a von Willebrand factor-cleaving protease. The mutant types of
p.P475S (c.1423C>T) polymorphism in ADAMTS13 have a reduced activity in
comparison with the wild type. In the present study, we investigated the
frequency of the C-to-T substitution in 2584 genomic DNA samples from 25 Asian,
European, and African populations using APLP (amplified product length
polymorphism) and/or HRM (high-resolution melting) assays. Allele T
(ADAMTS13(*)T) was detected only in Asian populations and its frequency was
observed to decrease gradually from north to south in 24 East Asian populations.
Almost all ADAMTS13(*)T were associated with ABO(*)O. These results suggested
that ADAMTS13(*)T had occurred on a chromosome with ABO(*)O in a northern part of
East Asia. This SNP is useful as an ancestry-informative marker, and the present
genotyping techniques are applicable to the investigation of an association
between this SNP and aortic dissection (Kobayashi et al., 2012).
PMID- 27497323
TI - IL-6 Contributes to Corneal Nerve Degeneration after Herpes Simplex Virus Type I
Infection.
AB - Herpes simplex virus type 1 (HSV-1) is a leading cause of neurotrophic keratitis
characterized by decreased corneal sensation because of damage to the corneal
sensory fibers. We and others have reported regression of corneal nerves during
acute HSV-1 infection. To determine whether denervation is caused directly by the
virus or indirectly by the elicited immune response, mice were infected with HSV
1 and topically treated with dexamethasone (DEX) or control eye drops. Corneal
sensitivity was measured using a Cochet-Bonnet esthesiometer and nerve network
structure via immunohistochemistry. Corneas were assessed for viral content by
plaque assay, leukocyte influx by flow cytometry, and content of chemokines and
inflammatory cytokines by suspension array. DEX significantly preserved corneal
nerve structure and sensitivity on infection. DEX reduced myeloid and T-cell
populations in the cornea and did not affect viral contents at 4 and 8 days post
infection. The elevated protein contents of chemokines and inflammatory cytokines
on infection were greatly suppressed by DEX. Subconjunctival delivery of
neutralizing antibody against IL-6 to infected mice resulted in partial
preservation of corneal nerve structure and sensitivity. Our study supports a
role for the immune response, but not local virus replication in the development
of HSV-1-induced neurotrophic keratitis. IL-6 is one of the factors produced by
the elicited inflammatory response to HSV-1 infection contributing to nerve
regression.
PMID- 27497326
TI - Forensic age prediction for dead or living samples by use of methylation
sensitive high resolution melting.
AB - Age prediction with epigenetic information is now edging closer to practical use
in forensic community. Many age-related CpG (AR-CpG) sites have proven useful in
predicting age in pyrosequencing or DNA chip analyses. In this study, a wide
range methylation status in the ELOVL2 and FHL2 promoter regions were detected
with methylation-sensitive high resolution melting (MS-HRM) in a labor-, time-,
and cost-effective manner. Non-linear-distributions of methylation status and
chronological age were newly fitted to the logistic curve. Notably, these
distributions were revealed to be similar in 22 living blood samples and 52 dead
blood samples. Therefore, the difference of methylation status between living and
dead samples suggested to be ignorable by MS-HRM. Additionally, the information
from ELOVL2 and FHL2 were integrated into a logistic curve fitting model to
develop a final predictive model through the multivariate linear regression of
logit-linked methylation rates and chronological age with adjusted R(2)=0.83.
Mean absolute deviation (MAD) was 7.44 for 74 training set and 7.71 for 30
additional independent test set, indicating that the final predicting model is
accurate. This suggests that our MS-HRM-based method has great potential in
predicting actual forensic age.
PMID- 27497327
TI - An autopsy case of zinc chloride poisoning.
AB - Ingestion of large amounts of zinc chloride causes corrosive gastroenteritis with
vomiting, abdominal pain, and diarrhea. Some individuals experience shock after
ingesting large amounts of zinc chloride, resulting in fatality. Here, we present
the results of an administrative autopsy performed on a 70-year-old man who
ingested zinc chloride solution and died. After drinking the solution, he
developed vomiting, abdominal pain, and diarrhea, and called for an ambulance.
Except for tachycardia, his vital signs were stable at presentation. However, he
developed hypotension and severe metabolic acidosis and died. The patient's blood
zinc concentration on arrival was high at 3030MUg/dL. Liver cirrhosis with cloudy
yellow ascites was observed, however, there were no clear findings of
gastrointestinal perforation. The gastric mucosa was gray-brown, with sclerosis
present in all gastric wall layers. Zinc staining was strongly positive in all
layers. There was almost no postmortem degeneration of the gastric mucosal
epithelium, and hypercontracture of the smooth muscle layer was observed.
Measurement of the zinc concentration in the organs revealed the highest
concentration in the gastric mucosa, followed by the pancreas and spleen.
Clinically, corrosive gastroenteritis was the cause of death. However, although
autopsy revealed solidification in the esophagus and gastric mucosa, there were
no findings in the small or large intestine. Therefore, metabolic acidosis
resulting from organ damage was the direct cause of death.
PMID- 27497328
TI - TPH1 A218 allele is associated with suicidal behavior in Turkish population.
AB - BACKGROUND: Serotonergic dysfunction is implicated in depression, psychiatric
disorders and suicidal behaviors. The first and rate-limiting step in the
synthesis of serotonin is catalyzed by tryptophan hydroxylase (TPH) which is
encoded by TPH1 and THP2 genes. Genetic association studies have revealed
contradictory results about the effect of the TPH1 A218C (rs1800532) polymorphism
on suicidal behavior in different populations. MATERIAL AND METHOD: In this
study, we investigated A218C polymorphism in 109 suicide attempters and 98
healthy controls. Socio-demographic characteristics of participants were obtained
through questionnaire. DNA was extracted from peripheral blood and genotyping was
performed by Real Time PCR. Fisher's exact test was used to evaluate the
significance of the difference among the independent variables. Hardy-Weinberg
equilibrium was tested using Pearson's goodness-of-fit chi-squared test. RESULTS:
The frequency of A allele was significantly higher in suicide attempters than
controls (46.33% vs. 35.71%, p=0.0357). However, there were no differences in
genotype frequencies of this locus between participants having attempted suicide
and controls (p>0.05). Among males, frequencies of CC genotype and C allele were
found to be significantly higher in controls (p=0.0125, p=0.0298). With regard to
the female subjects and female controls, no significant association was detected
between suicidal behavior and genotype/allele frequencies (p>0.05). CONCLUSION:
Our results provide evidence that A allele of TPH1 A218C polymorphism may be
associated with suicidal behavior in Turkish population.
PMID- 27497329
TI - Acute restraint stress provokes sudden cardiac death in normotensive rats and
enhances susceptibility to arrhythmogenic effects of adrenaline in spontaneously
hypertensive rats.
AB - BACKGROUND: A high incidence of cardiovascular events and sudden cardiac death
(SCD) has been reported following unexpected acute psychosocial stress. The
possible pathways by which acute restraint stress (ARS), a kind of acute
psychosocial stress, leads to SCD were determined. METHODS: Using 16-week-old
male normotensive Wistar Kyoto rats (WKY, n=24) as controls and spontaneously
hypertensive rats (SHR, n=24) as the hypertensive subjects with left ventricular
hypertrophy (LVH), we assessed ARS-related incidence of SCD, cardiac and
myocardial autonomic nervous system dysfunction, gap junction connexin-43 (Cx43)
channel remodeling, and ventricular repolarization abnormality, based on
electrocardiography, an adrenaline test, heart rate variability (HRV), and
reverse transcriptase polymerase chain reaction analyses. Rats with ARS were
introduced into restrainers that allowed head, limb, and tail movement. RESULTS:
In normotensive hearts without LVH, ARS induced a higher incidence of SCD
attributed to lethal bradycardia, increased cardiac and myocardial sympathetic
activation, and gap junction Cx43 channel remodeling, as evidenced by the
increases in the ratio of low-frequency and high-frequency powers in HRV, the
ratio of myocardial neuropeptide Y (NPY) and acetylcholinesterase (AChE) mRNA
expressions, and the up-regulation of LV Cx43 mRNA expression; in hypertensive
hearts with LVH, ARS enhanced susceptibility to the malignant arrhythmogenic
effects of the adrenaline test (a kind of sympathetic stimuli) accompanied by
abnormal ventricular repolarization, as evidenced by increased incidence of
ventricular tachycardia and/or ventricular fibrillation during the adrenaline
test and prolonged QTc immediately after ARS. CONCLUSIONS: ARS may trigger
cardiac and myocardial sympathetic predominance, and then induce gap junction
Cx43 channel remodeling, finally leading to lethal bradycardia in normotensive
WKY. ARS-induced abnormal ventricular repolarization may be responsible for ARS
enhanced susceptibility to sympathetic stimulation in SHR with LVH. Expressions
of myocardial NPY, AChE, and Cx43 genes, HRV, QTc and LVH measures showed
diagnostic and prognostic potential for predicting ARS-induced SCD.
PMID- 27497330
TI - Y-STR markers from Ladakh in the Himalayas.
AB - A total of 223 samples from the general population of Ladakh in Northwestern
India were amplified at 17 Y-STR loci using the AmpFlSTR(r) YfilerTM system. The
DNA profiles generated were employed to generate allelic frequencies, gene
diversity, haplotype diversity and discrimination capacity values as well as
number of different haplotypes, fraction of unique haplotypes and Rst pair wise
genetic distances. Multidimensional Scaling (MDS) and Correspondence Analysis
(CA) were performed with the Rst values and allelic frequencies, respectively.
The 17-loci discrimination capacity of Ladakh was found to be 0.8093. Eleven out
of the 16 loci have diversity values greater than 0.6, and 13 loci possess values
greater than 0.5. Ladakh exhibits no significant genetic difference to seven of
the 15 reference forensic databases after Bonferroni correction, three of which
are located in South Central Asian and four are from the Himalayan region. Rst
genetic distance values before and after Bonferroni corrections illustrate the
capacity of the Yfiler system to discriminate among Himalayan populations. The
intermediate position of the Ladakh population in the MDS and CA plots likely
reflects genetic flow and admixture with neighboring populations. In addition,
the longitudinal partition of populations in the MDS and CA plots likely reflect
human dispersals such as the silk road migrations.
PMID- 27497331
TI - Sudden death due to rupture of the right internal carotid artery in
neurofibromatosis type 1: A case report.
AB - Vascular involvement is a well-recognized manifestation of neurofibromatosis type
1 (NF1) which has the potential to be fatal when disrupted. We here present a
case of sudden death due to the fatal arterial rupture resulted from infiltration
of the neurofibromas. A 42-year-old man who suffered from NF1 presented a 1-h
history of sudden onset of pain in his right cervical region. His condition
worsened and became unconscious on his way to the emergency room. Despite
resuscitation efforts, he died 30min later without regaining consciousness.
Autopsy examination showed that a neurofibroma located around the right internal
carotid artery, confirmed immunohistochemically with S-100, vimentin and CD34.
Furthermore, proliferation of spindle cells positive for S-100 was seen in the
wall of right internal carotid artery, which was disrupted and resulted in a
hemorrhage. These findings suggest that the artery was disrupted by neurofibromas
in the vascular wall, which led to fragility of the vessel. On the basis of these
findings, we concluded that the cause of death was asphyxia resulting from airway
obstruction compressed by the hematoma due to the arterial rupture. As the
locality of the neurofibroma and hemorrhage were closed to the carotid
baroreflex, we considered another possible mechanism of his sudden death, which
could be cardiac inhibition induced by vagal stimulation. We hope this case will
increase recognition of NF-1 vasculopathy when encountering any sudden death in
NF1 patients.
PMID- 27497332
TI - An autopsy case of acetyl fentanyl intoxication caused by insufflation of
'designer drugs'.
AB - We present a fatal case of intoxication due to insufflation of acetyl fentanyl.
His blood concentration of acetyl fentanyl was 270ng/mL, and the manner of death
was classified as an accident. This is the first report of an autopsy case of
acetyl fentanyl delivered by insufflation, rather than intravenous
administration. He had been snoring loudly for at least 12h prior to death, and
transport to a hospital during this time and treatment with naloxone may have
saved his life. In this sense, it can be said that his death was preventable.
This case reemphasizes the risk of death associated with drug overdose and the
narrow range of acetyl fentanyl between the effective dose (ED50) and lethal dose
(LD50). The case should also raise awareness among medical professionals of the
effectiveness of naloxone and the need to establish a comprehensive system for
toxicological analysis while keeping the possibility of use of 'designer drugs'
in mind.
PMID- 27497333
TI - Assessment of sex in a modern Turkish population using cranial anthropometric
parameters.
AB - The utilization of radiological imaging methods in anthropometric studies is
being expanded by the application of modern imaging methods, leading to a
decrease in costs, a decrease in the time required for analysis and the ability
to create three-dimensional images. This retrospective study investigated 400
patients within the 18-45-years age group (mean age: 30.7+/-11.2years) using
cranial computed tomography images. We measured 14 anthropometric parameters
(basion-bregma height, basion-prosthion length, maximum cranial length and
cranial base lengths, maximum cranial breadth, bizygomatic diameter, upper facial
breadth, bimastoid diameter, orbital breadth, orbital length, biorbital breadth,
interorbital breadth, foramen magnum breadth and foramen magnum length) of
cranial measurements. The intra- and inter-observer repeatability and consistency
were good. From the results of logistic regression analysis using morphometric
measurements, the most conspicuous measurements in terms of dimorphism were
maximum cranial length, bizygomatic diameter, basion-bregma height, and cranial
base length. The most dimorphic structure was the bizygomatic diameter with an
accuracy rate of 83% in females and 77% in males. In this study, 87.5% of females
and 87.0% of males were classified accurately by this model including four
parameters with a sensitivity of 91.5% and specificity of 85.0%. In conclusion,
CT cranial morphometric analysis may be reliable for the assessment of sex in the
Turkish population and is recommended for comparison of data of modern
populations with those of former populations. Additionally, cranial morphometric
data that we obtained from modern Turkish population may reveal population
specific data, which may help current criminal investigations and identification
of disaster victims.
PMID- 27497334
TI - Population genetic study for 24 STR loci and Y indel (GlobalFilerTM PCR
Amplification kit and PowerPlex(r) Fusion system) in 1000 Korean individuals.
AB - Allele frequencies for 23 autosomal short tandem repeat loci (D3S1358, vWA,
D16S539, CSF1PO, TPOX, D8S1179, D21S11, D18S51, TH01, FGA, D5S818, D13S317,
D7S820, D2S441, D19S433, D22S1045, D10S1248, D1S1656, D12S391, D2S1338, SE33,
Penta D, Penta E), 1 Y-chromosome short tandem repeat locus (DYS391) and Y indel
were obtained from 1000 unrelated individuals of the Korean population.
PMID- 27497335
TI - Estimation of stature and sex from scapular measurements by three-dimensional
volume-rendering technique using in Chinese.
AB - In order to develop population - specific discriminant function equations and
stature prediction equations for predicting sex and stature from measurements of
the scapula in a contemporary Chinese, 414 individual 3D CT images were collected
from participants undergoing routine examination. Sex differences for the
variables were tested by Student's t-test. Fisher's method has been followed for
discriminant analysis. Regression analysis was applied to match the six linear
parameters against stature. The stepwise analysis of all measurements yielded a
sex classification accuracy rate of 86.7% and a sex bias of 3.1%. All the
classification accuracy rates of the univariate discriminant function analyses
are of more than 80%. For stature estimation, the accuracy of stature prediction
ranged from 5.252 to 7.210cm for male, from 4.630 to 6.484cm for female,
respectively. This paper provides indications that the scapula is an important
bone for sex diagnosis and it could be effectively used as alternatives in
forensic cases. Furthermore, the equations presented for stature estimation in
this study should be used as alternatives in forensic cases when long bones were
unavailable for stature estimation.
PMID- 27497336
TI - Medicolegal aspects of PMA-related deaths.
AB - Unlike amphetamine, amphetamine-like substances accessible on the drug market are
less expensive and more easily available; they also produce hallucinogenic
effects expected by the users. Such properties render them more attractive as
compared to amphetamine. On the other hand, the knowledge of the toxicity of
these compounds is very limited, what in consequence generates problems that
create ever-expanding research areas, including analytical, clinical and
medicolegal issues, thus leading to development of systemic databases. An example
here is paramethoxyamphetamine (PMA), which appeared on the drug market in recent
years as a result of creative inventiveness of producers of psychoactive
substances, who aimed at PMA replacing the popular ecstasy (MDMA) as a less
expensive and more available product. It is more potent than MDMA, but has a
slower onset of action, which encourages users to take more. The problem is
illustrated in the present paper by three fatal cases involving PMA, which were
comprehensively investigated taking into consideration case histories,
pathological and toxicological findings obtained with the use of LC-MS-MS method.
In blood samples taken from all the three victims, very high concentrations of
PMA were found (in the range of 10-27mg/L) and thus the cause of deaths was
determined as overdoses of PMA with the underlying mechanism of acute
cardiorespiratory failure.
PMID- 27497337
TI - A rare case of steering wheel injury causing coronal-plane pancreatic
lacerations.
AB - The incidence of pancreatic injury after blunt abdominal trauma is extremely low.
A timely and accurate diagnosis is important, as a delay could be life
threatening. In this case, a 70-year-old driver crashed a car into a concrete
wall at low speed. He was transported to the emergency hospital but died about
9.5h later with the cause of death unknown. An autopsy revealed that his pancreas
was lacerated in the coronal plane and there was mesenteric contusion. Cause of
death was determined to be blood loss resulting from pancreatic and mesenteric
contusion. The mechanism of the injury was considered to be a very rare
"degloving," caused by the impact from the steering wheel. It is therefore
important to keep in mind possible pancreatic damage when examining blunt trauma
to the abdomen, especially in traffic accident cases.
PMID- 27497338
TI - Analysis of 12 X-chromosomal markers in the population of central Croatia.
AB - Investigator(r) Argus X-12 Kit is a commercially available set that allows
simultaneous PCR amplification of 12 X-STR markers belonging to four linkage
groups (LG). To assess the forensic efficiency of these markers for the
population of central Croatia and consequent applicability in routine forensic
casework, DNA from 200 blood samples of unrelated donors (100 female and 100
male) was amplified by Investigator(r) Argus X-12 Kit and analyzed by capillary
electrophoresis. Statistical computations based on allele and haplotype
frequencies for LG1 - LG4 were performed using Arlequin 3.5 software and on-line
tool available at ChrX-STR.org. In female samples, all X-STR markers were in
Hardy-Weinberg equilibrium (HWE). The most informative marker for central Croatia
population was DXS10135 with polymorphism information content (PIC) 0.9296. The
least polymorphic locus was DXS8378 (PIC=0.6363). Power of discrimination (PD)
varied from 0.6968 to 0.9336 in male and from 0.8476 to 0.9916 in female samples.
Combined PD exceeded 0.999999999 in both men and women. In male samples, linkage
disequilibrium (LD) test revealed significant association (P=0.0000) of one
marker pair in LG4 and two marker pairs in LG3. Portion of observed haplotypes in
the number of possible haplotypes varied from 2.86% to 7.47% across all LGs. LG1
was the most informative with haplotype diversity (H) 0.9972. High PD of all
analyzed markers exhibited for central Croatia population confirms suitability of
Investigator(r) Argus X-12 for forensic pertinence. Moreover, results of this
study will be included in establishing a national reference X-STR database based
on 12 X-STR loci, which is necessary for the correct interpretation of the
forensic casework results.
PMID- 27497339
TI - Development of a preparation method to produce a single sample that can be
applied to both LC-MS/MS and GC-MS for the screening of postmortem specimens.
AB - Simple and efficient extraction methods have been developed for the screening of
a wide array of drugs in postmortem autopsy specimens. Acidic and basic compounds
were targeted with two extraction methods that can be applied to both GC-MS and
LC-MS/MS instrumentation. The extractions were achieved by utilizing lipid
removal and solid-phase extraction cartridges while carefully monitoring the pH
of the samples to ensure the adequate removal of interfering substances like
lipids and amino acid derivatives. These methods were applied to actual autopsy
cases, with 94 and 124 compounds detected by GC-MS and LC-MS/MS, respectively.
The developed methods could easily be incorporated into a forensic laboratory's
daily routine for screening many different compounds from postmortem samples.
PMID- 27497340
TI - Effect of granulocyte colony-stimulating factor priming combined with low-dose
cytarabine and homoharringtonine in higher risk myelodysplastic syndrome
patients.
AB - As sensitization of leukemia cells with granulocyte colony-stimulating factor (G
CSF) can enhance the cytotoxicity of chemotherapy in myeloid malignancies, a
pilot study was conducted in order to evaluate the effect of G-CSF priming
combined with low-dose chemotherapy in patients with higher risk myelodysplastic
syndrome (MDS). The regimen, G-HA, consisted of cytarabine (Ara-C) 7.5mg/m(2)/12h
by subcutaneous injection, days 1-14, homoharringtonine (HHT) 1.5mg/m(2)/day by
intravenous continuous infusion, days 1-14, and G-CSF 150mg/m(2)/day by
subcutaneous injection, days 0-14. 56 patients were enrolled, 34 patients (61%,
95% confidence interval: 51.44-70.56%) achieved complete remission (CR). Median
duration of neutropenia was 7days (ranging from 2 to 16days). Grade 1-2
nonhematologic toxicities were documented, including nausea and vomiting (5%),
liver function abnormality (5%), and heart function abnormality (2%). No central
nervous system toxicity was found. Mortality within the first 4 weeks was 4%. The
G-HA regimen is effective in remission induction for higher risk MDS patients and
well tolerated due to the acceptable toxicity in maintenance therapy in the
patients who cannot undergo Hematopoietic cell transplantation (HCT).
PMID- 27497341
TI - Influence of functional polymorphisms in DNA repair genes of myelodysplastic
syndrome.
AB - Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem
cell (HSC) malignances characterized by peripheral cytopenias and predisposition
to acute myeloid leukemia transformation. Several studies show that the MDS
pathogenesis is a complex and heterogeneous process that involves multiple steps
through a sequence of genetic lesions in the DNA which lead to functional changes
in the cell and the emergence and subsequent evolution of pre-malignant clone.
Double strand breaks (DSB) lesions are the most severe type of DNA damage in
HSCs, which, if not properly repaired, might contribute to the development of
chromosomal abnormalities, which in turn may lead to leukemia development. We
assessed the mRNA expression levels of ATM, BRCA1, BRCA2, RAD51, XRCC5, XRCC6 and
LIG4 genes in bone marrow samples of 47 MDS patients in order to evaluate the
association with functional polymorphisms rs228593, rs4793191, rs9567623,
rs1801320, rs3835, rs2267437 and rs1805388, respectively, and try to detect
clinical associations. We found that the rs228593, rs2267437 and rs1805388
functional polymorphisms probably alter the level of expression of the ATM, XRCC6
and LIG4 genes, respectively, being important in the maintenance of genomic
instability in MDS.
PMID- 27497342
TI - How are the kids holding up? A systematic review and meta-analysis on the
psychosocial impact of maternal breast cancer on children.
AB - BACKGROUND: Having a mother diagnosed with breast cancer can be a distressing
time for a child. This review examines the impact maternal breast cancer has on
the psychosocial functioning of children and what factors possibly moderate this
relationship. METHODS: Using PRISMA guidelines, five electronic databases were
systematically searched for published studies examining maternal breast cancer
and the psychosocial functioning of children. RESULTS: A total of 15 studies
contributed to the analysis. Results from a random effects meta-analysis show
that children experience marginally elevated internalizing problems (standardized
mean difference=.14, 95% CI .00, .28), significantly fewer total problem
behaviors (standardized mean difference=-.13, 95% CI -.23, -.03), and no changes
in externalizing problems (standardized mean difference=-.07, 95% CI -.19, .05)
relative to comparison groups. Consistent with this, the narrative review
suggests the children may experience elevated depression, anxiety and mental
distress yet show more social competence and little aggressive or disruptive
behavior. Significant moderating variables included informant type (i.e., self
ratings vs mother's ratings vs other's ratings) and comparison group used (i.e.,
controls vs normative data). There is also evidence that illness severity and
maternal mental health may impact the results. CONCLUSIONS: The results suggest
that children may be at risk for internalizing-type problems, especially when
their mother experiences depression and has serious medical complications.
Research using larger and more diverse samples is needed to fully understand how
maternal breast cancer impacts children.
PMID- 27497343
TI - Challenging the dogma of colorectal peritoneal metastases as an untreatable
condition: Results of a population-based study.
AB - PURPOSE: To determine the impact of the implementation of novel systemic regimens
and locoregional treatment modalities on survival at population level in
colorectal cancer (CRC) patients presenting with peritoneal metastases (PMs).
METHODS: All consecutive CRC patients with synchronous PM (<3 months) between
1995 and 2014 were extracted from the Eindhoven area of the Netherlands Cancer
Registry. Trends in treatment and overall survival were assessed in four time
periods. Multivariable regression analysis was used to analyse the impact of
systemic and locoregional treatment modalities on survival. RESULTS: A total of
37,036 patients were diagnosed with primary CRC between 1995 and 2014.
Synchronous PM was diagnosed in 1,661 patients, of whom 55% had also metastases
at other sites (n = 917) and 77% received anticancer therapy (n = 1,273).
Treatment with systemic therapy increased from 23% in 1995-1999 to 56% in 2010
2014 (p < 0.0001). Cytoreductive surgery with hyperthermic intraperitoneal
chemotherapy (CRS-HIPEC) was applied since 2005 and increased from 10% in 2005
2009 to 23% in 2010-2014. Surgery for lymphatic or haematogenous metastases
increased from 2% to 10% in these periods. Median overall survival of the
complete cohort improved from 6.0 months in 1995-2000 to 12.5 months in 2010-2014
(p < 0.0001), with a doubling of survival for both PM alone and PM with other
involved sites. The influence of year of diagnosis on survival (hazard ratio,
2010-2014 versus 1995-1999; 0.5, 95% confidence interval: 0.43-0.62; p < 0.0001)
disappeared after including systemic therapy and locoregional treatment
modalities in subsequent multivariable models. CONCLUSION: CRC patients
presenting with PM are increasingly offered a multidisciplinary treatment
approach, resulting in an increased overall survival for the entire cohort.
PMID- 27497344
TI - MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term
ophthalmic effects.
AB - BACKGROUND: Mitogen-activated protein kinase kinase (MEK) inhibitors have aroused
considerable interest in oncology. Activity has been demonstrated in various
types of cancer, especially melanoma. MEK inhibitors induce a transient
retinopathy, considered to be a class effect. At present, only sparse data are
available on retinal effects with long-term MEK inhibition. PATIENTS AND METHODS:
In this prospective, observational study, patients with advanced melanoma
participating in different phase 1/2 or phase 3 clinical trials were treated with
the MEK inhibitor binimetinib, with a v-Raf murine sarcoma viral oncogene homolog
B (BRAF) inhibitor, or with combination therapy. They underwent regular
ophthalmological examinations including determination of visual function,
biomicroscopy, dilated fundoscopy and optical coherence tomography (OCT) for a
period of up to 2 years. Retinopathy was diagnosed on defined OCT criteria.
RESULTS: Sixty-two patients were investigated between 1st October 2011 and 31st
July 2015: 13 were treated with the MEK inhibitor binimetinib alone, 10 with a
selective BRAF inhibitor, and 39 with combination therapy. In 92% of patients on
monotherapy and 100% of those on combination treatment, binimetinib caused dose
related lesions with serous neuroretinal detachments and oedema, strongly
dependent on the time after medication. With continued treatment, retinal volume
and thickness decreased to levels below baseline, without any apparent functional
deficits or changes in structural integrity. CONCLUSIONS: Binimetinib induces a
specific retinopathy with daily fluctuations depending on the time interval after
medication. The retinopathy partially recovers, but can still be detected many
months later. Retinal thinning, possible first signs of retinal atrophy have been
observed after long-term treatment, but, so far, without functional relevance.
PMID- 27497345
TI - Tumour-free margins in vulvar squamous cell carcinoma: Does distance really
matter?
AB - BACKGROUND: There is no consensus on the width of tumour-free margins after
surgery for vulvar squamous cell carcinoma (VSCC). Most current guidelines
recommend tumour-free margins of >=8 mm. The aim of this study was to investigate
whether a margin of <8 mm is associated with an increased risk of local
recurrence in VSCC. METHODS: A meta-analysis of the available literature and a
cohort study of 148 VSCC patients seen at a referral centre from 2000 to 2012 was
performed. The primary end-point of the cohort study was a histologically
confirmed ipsilateral local recurrence within 2 years after primary treatment in
relation to the margin distance. RESULTS: Based on 10 studies, the meta-analysis
showed that a tumour-free margin of <8 mm is associated with a higher risk of
local recurrence compared to a tumour-free margin of >=8 mm (pooled risk ratio,
1.99 [95% confidence interval {CI}: 1.13-3.51], p = 0.02). In the cohort study,
we found no clear difference in the risk of local recurrence in the <8 versus >=8
mm group; however, 40% of the patients in the <8 mm group received additional
treatment. Tumour-positive margin was the only independent risk factor for local
recurrence in the multivariable analysis (hazard ratio, 0.21 [95% CI: 0.08
0.55]). CONCLUSIONS: This work provides important data to question the commonly
used 8-mm margin as a prognosticator for local recurrence. More research is
needed to address the question of whether additional treatment improves the
prognosis in patients with a tumour-free margin of <8 mm.
PMID- 27497346
TI - Assessment of trauma quality improvement activities at public hospitals in
Thailand.
AB - BACKGROUND: Given the current exceptional burden of injury in Thailand, the
proven efficacy of quality improvement programs, and the current scarcity of
national-level information on trauma quality improvement program (TQIP)
implementation in Thailand, we aimed to examine the use of TQIPs and barriers to
TQIP adoption in Thai public trauma centers. METHODS: We distributed a survey to
110 public hospitals which are designated to provide trauma care in Thailand. The
survey assessed the presence or absence of the four core elements of the World
Health Organization (WHO) recommended TQIPs (morbidity and mortality (M&M)
conferences, preventable death panels, trauma registries, and audit filters), and
provider perception of barriers and priorities in TQIP implementation. RESULTS:
Responses were received from 80 (72%) respondents. Seventy-two (90%) reported
having a trauma registry and seventy (88%) respondents reported use of audit
filters. Seventy (88%) respondents reported conducting regular M&M conferences,
and 45 (56%) respondents reported the presence of preventable death panels.
Thirty-eight (48%) respondents reported presence of all four elements of WHO
TQIPs. The most commonly reported barriers to implementing TQIPs were lack of
interest (55; 68%) and lack of time (39; 48%)to implement TQIPs. Audit filters
were reported by only 25 (31%) of respondents and optimization of audit filters
was the most frequently identified next-step in further development of TQIP.
CONCLUSIONS: Just under half of responding Thai public trauma centers reported
implementation of all four elements of the WHO recommended TQIPs. Priority
strategies to facilitate TQIP maturation in Thailand should address staff
motivation, provision of staff time for TQIP development, and optimization of
audit filter use to monitor quality of care.
PMID- 27497347
TI - Extracellular polymeric substances facilitate the biosorption of phenanthrene on
cyanobacteria Microcystis aeruginosa.
AB - Phytoplankton-derived extracellular polymeric substances (EPS) are of vital
importance for the biogeochemical cycles of hydrophobic organic pollutants in
lake ecosystems. In this study, roles of loosely-bound EPS (LB-EPS) and tightly
bound EPS (TB-EPS) in biosorption of phenanthrene (PHE) on a typical
cyanobacteria Microcystis aeruginosa were investigated. The results showed that
the biosorption of PHE on M. aeruginosa cell varied lasted 24 h, while the
binding of PHE to LB-EPS and TB-EPS reached equilibrium within less than 2 h. The
equilibrium biosorption capacities of M. aeruginosa cell, LB-EPS and TB-EPS were
6.78, 12.31, and 9.47 MUg mg(-1), respectively, indicating that the binding of
PHE to EPS was a considerable process involved in biosorption. Fluorescence
quenching titration revealed that increasing temperature induced more binding
sites in EPS for PHE and the binding process was driven by electrostatic force
and hydrophobic interactions. Interestingly, dynamic and static quenching
processes occurred simultaneously for the binding of PHE to protein-like
substances in EPS, whereas the binding of PHE to humic-like substances belonged
to static quenching. The relatively higher contents of proteins in LB-EPS
produced a stronger binding capacity of PHE. Overall, the interactions between
hydrophobic organic pollutants and cyanobacterial EPS are favorable to the
bioaccumulation of hydrophobic organic pollutants in cyanobacteria and facilitate
the regulatory function of cyanobacterial biomass as a biological pump.
PMID- 27497348
TI - A key parameter on the adsorption of diluted aniline solutions with activated
carbons: The surface oxygen content.
AB - A total of 11 different commercial activated carbons (AC) with well characterized
textural properties and oxygen surface content were tested as adsorbents for the
removal of aniline as a target water pollutant. The maximum adsorption capacity
of aniline for the studied AC was from 138.9 to 257.9 mg g(-1) at 296.15 K and it
was observed to be strongly related to the textural properties of the AC, mainly
with the BET surface area and the micropore volume. It was not observed any
influence of the oxygen surface content of the AC on the maximum adsorption
capacity. However, it was found that at low aniline aqueous concentration, the
presence of oxygen surface groups plays a dominant role during the adsorption. A
high concentration of oxygen surface groups, mainly carboxylic and phenolic
groups, decreases the aniline adsorption regardless of the surface area of the
AC.
PMID- 27497349
TI - Modeling of experimental data on trace elements and organic compounds content in
industrial waste dumps.
AB - The main objective of the study presented was to investigate the differences
between 20 mine waste dumps located in the Silesian Region of Poland and Czech
Republic, in terms of trace elements and polycyclic aromatic hydrocarbons
contents. The Principal Component Analysis and Hierarchical Clustering Analysis
were applied in exploration of the studied data. Since the data set was affected
by outlying objects, the employment of a relevant analysis strategy was
necessary. The final PCA model was constructed with the use of the Expectation
Maximization iterative approach preceded by a correct identification of outliers.
The analysis of the experimental data indicated that three mine waste dumps
located in Poland were characterized by the highest concentrations of
dibenzo(g,h,i)anthracene and benzo(g,h,i)perylene, and six objects located in
Czech Republic and three objects in Poland were distinguished by high
concentrations of chrysene and indeno (1.2.3-cd) pyrene. Three of studied mine
waste dumps, one located in Czech Republic and two in Poland, were characterized
by low concentrations of Cr, Ni, V, naphthalene, acenaphthene, fluorene,
phenanthrene, anthracene, fluoranthen, benzo(a)anthracene, chrysene, benzo (b)
fluoranthene, benzo (k) fluoranthene, benzo(a)pyrene, dibenzo(g,h,i)anthracene,
benzo(g,h,i)perylene and indeno (1.2.3-cd) pyrene in comparison with the
remaining ones. The analysis contributes to the assessment and prognosis of
ecological and health risks related to the emission of trace elements and organic
compounds (PAHs) from the waste dumps examined. No previous research of similar
scope and aims has been reported for the area concerned.
PMID- 27497350
TI - Concentrations and patterns of polychlorinated naphthalenes in urban air in
Beijing, China.
AB - Air samples were collected, using a high-volume air sampler, at an urban site in
Beijing from April 2014 to March 2015. The polychlorinated naphthalene (PCN)
concentration in the atmosphere in each season was determined. The total PCN
(total target tri- to octachloronaphthalene congeners) concentrations were 1.99
19.0 pg/m(3), and the mean was 7.20 pg/m(3). The PCN concentrations were higher
in fall than summer, indicating that the concentrations varied significantly over
time. The trichloronaphthalene homolog was the predominant PCN homolog in all
four seasons. The PCN toxic equivalent (TEQ) concentrations were 0.42-6.89
fg/m(3), and the mean was 1.74 fg/m(3). The CN-66/67 and CN-73 congeners were the
predominant contributors to the TEQ concentrations. The mean seasonal TEQ
concentration decreased in the order fall (3.18 fg/m(3)) > winter (1.41 fg/m(3))
> summer (1.11 fg/m(3)) > spring (1.03 fg/m(3)). The TEQ concentrations and the
PCN concentrations did not follow the same seasonal trends, but the highest TEQ
and PCN concentrations were both found in fall. Correlation analysis, ratio
analysis, and principal component analysis were used to investigate the sources
of PCNs to the Beijing atmosphere. The results suggested that combustion
processes may be the main sources of PCNs to the Beijing atmosphere.
PMID- 27497351
TI - Experimental study of clay-hydrocarbon interactions relevant to the
biodegradation of the Deepwater Horizon oil from the Gulf of Mexico.
AB - Adding clay to marine oil pollution represents a promising approach to enhance
bacterial hydrocarbon degradation in nutrient poor waters. In this study, three
types of regionally available clays (Ca-bentonite, Fuller's Earth and kaolin)
were tested to stimulate the biodegradation of source and weathered oil collected
from the Deepwater Horizon spill. The weathered oil showed little biodegradation
prior to experimentation and was extensively degraded by bacteria in the
laboratory in a similar way as the alkane-rich source oil. For both oils, the
addition of natural clay-flakes showed minor enhancement of oil biodegradation
compared to the non-clay bearing control, but the clay-oil films did limit
evaporation. Only alkanes of a molecular weight (MW) > 420 showed significant
reduction by enhanced biodegradation following natural clay treatment. In
contrast, all fertilized clay flakes showed major bacterial degradation of the
oil, with a 6-10 times reduction in alkane content, and an up to 8 fold increase
in the rate of O2 consumption. Compared to the control, such treatment showed
particular reduction of longer chained alkanes (MW > 226). The application of
natural and fertilized clay flakes also showed selective reduction of PAHs,
mainly in the MW range of 200-300, but without significant change in the toxicity
indices measured. These results imply that a large variety of clays may be used
to boost oil biodegradation by aiding attachment of fertilizing nutrients to the
oil.
PMID- 27497352
TI - Too little too late for young women with STEMI.
PMID- 27497353
TI - The modern approach to endovascular carotid revascularisation.
PMID- 27497354
TI - Longer pre-hospital delays and higher mortality in women with STEMI: the e-MUST
Registry.
AB - AIMS: The mortality rate in patients with STEMI is higher in women than in men.
This higher mortality rate is partly accounted for by certain known
characteristics inherent in the female population (age, diabetes). Using data
from the e-MUST registry on STEMI patients in the Greater Paris area, we assessed
the differences between men and women treated with reperfusion strategies.
METHODS AND RESULTS: Patients presenting within 24 hours of pain onset between
2006 and 2010 were included in the study. The male and female subpopulations were
compared according to their baseline characteristics, their management delays and
their early outcomes. Five thousand eight hundred and forty males (78.9%) and
1,557 females (21.1%) were included in the study. In-hospital mortality was
significantly higher in women than in men, 143 (9.4%) vs. 254 (4.4%), p<0.0001,
with a longer time to treatment initiation, symptoms to call (2.7+/-3.6 vs. 2.2+/
3.4 hours, p<0.0001), symptoms to first medical contact (FMC) (3.1+/-3.7 vs.
2.6+/-3.4 hours, p<0.0001), and call to FMC (25.6+/-23.5 vs. 23.6+/-18.3 min,
p=0.02). After adjustment for clinical factors, severity criteria, myocardial
infarction (MI) location and delays, mortality remained higher in women than in
men with an odds ratio of 1.40 [1.06-1.84], p=0.017. CONCLUSIONS: We demonstrated
longer pre-hospital delays and higher in-hospital mortality in women. The
increase in the time to treatment alone does not completely explain the
persistent increase in mortality. Further studies, public awareness programmes
and physician education are necessary to reduce delays and improve the prognosis
of STEMI in women.
PMID- 27497355
TI - Two-year clinical outcomes of Absorb bioresorbable vascular scaffold implantation
in complex coronary artery disease patients stratified by SYNTAX score and ABSORB
II study enrolment criteria.
AB - AIMS: This study presents the two-year clinical outcomes of the Amsterdam ABSORB
registry stratified by lesion and patient characteristics complexity (SYNTAX
score and ABSORB II study enrolment criteria). METHODS AND RESULTS: Patients
treated with BVS were included in this prospective registry and stratified
according to the ABSORB II trial inclusion and exclusion criteria and the SYNTAX
score. The registry comprises 135 patients (59+/-11 years, 73% male, 18%
diabetic) with 159 lesions. Median follow-up duration was 774 days (742-829).
Median SYNTAX score was 11.5 (Q1-Q3: 6-17.5). Two-year event rates were cardiac
death 0.7%, MI 5.3%, TVR 13.6%, TLR 11.4%, definite ST 3.0% and TVF 14.4%,
respectively. Stratified analyses showed a significantly higher revascularisation
rate in patients not meeting ABSORB II criteria (TVR: 2.3% vs. 19.2%, p=0.010,
and TLR: 2.3% vs. 15.8%, p=0.025) and patients with SYNTAX score >=11.5 (TVR:
4.8% vs. 21.8%, p=0.006, and TLR: 3.2% vs. 17.4%, p=0.007). CONCLUSIONS: The use
of Absorb BVS in patients meeting the ABSORB II trial inclusion criteria or those
with low SYNTAX scores is associated with acceptable clinical outcomes at two
year follow-up. Patients with more complex characteristics have significantly
higher revascularisation rates.
PMID- 27497356
TI - Absorb vs. DESolve: an optical coherence tomography comparison of acute
mechanical performances.
AB - AIMS: The aim of the study was to compare retrospectively the acute mechanical
performance of the Absorb vs. DESolve scaffolds in terms of appropriate
deployment with OCT. METHODS AND RESULTS: Final post-deployment OCT pullbacks of
consecutive patients treated with either Absorb or DESolve were reviewed. The
following parameters were calculated and compared: mean and minimal lumen area
(MLA), residual in-scaffold area stenosis (RAS), incomplete strut apposition
(ISA), tissue prolapse area, eccentricity index, asymmetry index, strut fracture
and edge dissection. A total of 72 patients were included. The Absorb group
consisted of 35 patients treated with 63 Absorb scaffolds and was compared to a
well-matched group of 37 patients treated with 50 DESolve scaffolds. Baseline
characteristics did not differ significantly between the two groups. Procedural
characteristics were different with respect to maximal balloon inflation pressure
(Absorb vs. DESolve: 21.5+/-0.4 atm vs. 16.8+/-3.8 atm, p<0.01) and mean NC
balloon diameter used for post-dilatation (Absorb vs. DESolve 3.3+/-0.4 mm vs.
3.5+/-0.4 mm, p<0.01). OCT analysis showed similar MLA (Absorb vs. DESolve: 5.8+/
1.9 mm2 vs. 6.1+/-2.6 mm2, p=0.43) and mean luminal area (Absorb vs. DESolve:
7.1+/-2.2 mm2 vs. 7.2+/-1.9 mm2, p=0.77). The mean eccentricity index was 0.85+/
0.05 with Absorb and 0.80+/-0.05 with DESolve, p<0.01. There was no difference in
the incidence of overall ISA. A smaller prolapse area was found with Absorb
(Absorb vs. DESolve 1.0+/-1.1 mm2 vs. 3.6+/-6.2 mm2, p<0.01). CONCLUSIONS: The
two scaffolds showed similar MLA while there was a trend towards a lower RAS and
a larger maximum and minimum scaffold diameter with DESolve. The DESolve scaffold
was more eccentric as compared to the Absorb. These results might be related to
the DESolve's unique expansion properties or they may reflect baseline and
procedural differences which cannot be excluded in a retrospective study.
Randomised studies are needed to address this aspect.
PMID- 27497357
TI - Evaluation of vascular healing of polymer-free sirolimus-eluting stents in native
coronary artery stenosis: a serial follow-up at three and six months with optical
coherence tomography imaging.
AB - AIMS: Our aim was to assess vascular response after polymer-free sirolimus
eluting stent (SES) implantation by using an optical coherence tomography (OCT)
derived vascular healing score (HS), quantifying the deficiency of healing.
METHODS AND RESULTS: In a prospective, multicentre, single-arm, open-label study,
OCT examinations were performed at three months in 45 patients (47 lesions). Per
protocol, 24 lesions which had not reached adequate vascular healing according to
study criteria were scheduled for OCT examination at six months. The HS was
calculated at two time points. Serial OCT imaging demonstrated that the
proportion of covered stent struts increased from a median of 87.1% at three
months to 98.6% at six months (p<0.001). The neointimal thickness increased from
a median of 82.8 um to 112.2 um (p<0.001), whereas the median percentages of
malapposed struts were 0.2% and 0.0% at the two respective time points.
Neointimal volume obstruction increased from 6.3% to 12.8%, and the HS decreased
from a median of 28.1 at three months to 2.4 at six months. CONCLUSIONS: In
patients who had inadequate vascular healing three months after polymer-free SES
implantation, serial OCT showed almost complete vascular healing at six months.
PMID- 27497358
TI - Evaluation of myocardial blood flow and coronary flow reserve after implantation
of a bioresorbable vascular scaffold versus metal drug-eluting stent: an interim
one-month analysis of the VANISH trial.
AB - AIMS: A randomised clinical trial of bioresorbable vascular scaffold (BVS) vs.
metal drug-eluting stent (DES) was initiated, using positron emission tomography
(PET) perfusion imaging to assess the effects of both treatments on (hyperaemic)
myocardial blood flow (MBF) and coronary flow reserve (CFR) over a three-year
period (VANISH trial). In the present study, early, i.e., after one month, MBF
and CFR are reported. METHODS AND RESULTS: Sixty patients (45 men [75%], 55+/-7
years) with a documented single-vessel type A or B1 lesion were included in this
single-blind randomised clinical trial. Patients were randomised to implantation
of a BVS or DES in a one-to-one fashion. Approximately one month after
percutaneous coronary intervention, patients underwent [15O]H2O PET to assess
(hyperaemic) MBF, cold pressor test MBF, and CFR. One patient refused PET
perfusion at one-month follow-up (in the DES arm). MBF of the treated myocardial
territory during rest, CPT, and hyperaemia were not different in BVS-treated
patients as compared to DES-treated patients (1.02+/-0.28 vs. 0.96+/-0.24 mL.min
1.g-1, p=0.38, 1.20+/-0.38 vs. 1.08+/-0.23 mL.min-1.g-1, p=0.16, and 3.04+/-0.80
vs. 3.33+/-0.77 mL.min-1.g-1, p=0.16, respectively). CFR of the treated
myocardial territory was significantly lower in the BVS-treated patients (3.09+/
0.94 vs. 3.57+/-0.85, p<0.05). CONCLUSIONS: No differences in PET-derived
absolute myocardial perfusion were observed between BVS-treated patients as
compared to DES-treated patients at one-month follow-up. CFR was attenuated in
BVS-treated patients, although still within the normal range.
PMID- 27497359
TI - Angiographic complexity of coronary artery disease according to SYNTAX score and
clinical outcomes after revascularisation with newer-generation drug-eluting
stents: a substudy of the BIOSCIENCE trial.
AB - AIMS: We sought to assess the performance of drug-eluting stents combining an
ultrathin cobalt-chromium platform with a biodegradable polymer across categories
of increasing SYNTAX score (SS). METHODS AND RESULTS: Patients included in the
BIOSCIENCE trial and randomly allocated to treatment with biodegradable polymer
sirolimus-eluting stents (BP-SES) or durable polymer everolimus-eluting stents
(DP-EES) were categorised according to SS tertiles (low <8, medium 8-15, high
>15). The primary endpoint, target lesion failure (TLF), was defined as a
composite of cardiac death, target vessel myocardial infarction and clinically
indicated target lesion revascularisation. The patient-oriented endpoint (POCE)
included death, myocardial infarction, or any repeat revascularisation. The SS
was available in 2,041 out of 2,119 patients (96.3%). At two-year follow-up,
patients with an SS >15 experienced higher rates of both TLF and POCE as compared
to patients with medium and low SS (14.5% vs. 8.1% and vs. 5.9%, p<0.001; 22.7%
vs. 14.9% and vs. 12.4%; p<0.001), respectively. Comparable rates of the
composite endpoints were documented for both stent types in each category of SS.
CONCLUSIONS: Increasing lesion complexity as assessed by SS was associated with
higher rates of TLF and POCE in a contemporary PCI population with minimal
exclusion criteria. BP-SES and DP-EES showed comparable performance across the
entire spectrum of CAD severity.
PMID- 27497360
TI - Early coverage of drug-eluting stents analysed by optical coherence tomography:
evidence of the impact of stent apposition and strut characteristics on the
neointimal healing process.
AB - AIMS: Previous studies have associated issues such as incomplete stent apposition
with delayed healing and adverse events (stent thrombosis). The aim of this study
was to evaluate the impact of strut apposition and stent type on the progression
of stent strut coverage. METHODS AND RESULTS: We evaluated in vivo in porcine
models the follow-up response and coverage characteristics of well-apposed and
malapposed segments of drug-eluting stents (DES) (CYPHER, PROMUS Element and
Orsiro) and the Absorb bioresorbable vascular scaffold (BVS) by optical coherence
tomography (OCT) sequentially, at baseline, and at one week and four weeks of
follow-up. Supporting results were provided by histological analysis performed at
four-week follow-up and computer simulation describing the shear characteristics
around apposed and non-apposed struts. A total of 325 cross-sections containing
3,166 struts were analysed. The extent of malapposition decreased over time as a
result of neointimal healing (from 7.1% at baseline to 0% at four weeks; p=0.03).
At one week, 13.6% of struts in well-apposed segments were still uncovered versus
19.2% of struts in malapposed cross-sections and 77.8% of NASB struts (p<0.01).
At four-week follow-up, 3.1% of struts were uncovered in well-apposed cross
sections vs. 1.6% in malapposed cross-sections and 35.7% of NASB struts (p<0.01).
A comparison of the apposed segments revealed that the thin-strut Orsiro had only
1.3% of uncovered struts at one week while PROMUS Element, CYPHER and BVS had
6.6%, 48.4% and 16.2% of struts still uncovered, respectively. CONCLUSIONS: This
study shows that early coverage is influenced by stent apposition as well as
platform strut characteristics (stent type). At four weeks, NASB struts remained
a focus of delayed endothelialisation.
PMID- 27497361
TI - Direct implantation of rapamycin-eluting stents with bioresorbable drug carrier
technology utilising the Svelte coronary stent-on-a-wire: the DIRECT II study.
AB - AIMS: Our aim was to demonstrate the safety and efficacy of the Svelte sirolimus
eluting coronary stent-on-a-wire Integrated Delivery System (IDS) with
bioresorbable drug coating compared to the Resolute Integrity zotarolimus-eluting
stent with durable polymer in patients with de novo coronary artery lesions.
METHODS AND RESULTS: Direct stenting, particularly in conjunction with
transradial intervention (TRI), has been associated with reduced bleeding
complications, procedure time, radiation exposure and contrast administration
compared to conventional stenting with wiring and predilatation. The low-profile
Svelte IDS is designed to facilitate TRI and direct stenting, reducing the number
of procedural steps, time and cost associated with coronary stenting. DIRECT II
was a prospective, multicentre trial which enrolled 159 patients to establish non
inferiority of the Svelte IDS versus Resolute Integrity using a 2:1
randomisation. The primary endpoint was angiographic in-stent late lumen loss
(LLL) at six months. Target vessel failure (TVF), as well as secondary clinical
endpoints, will be assessed annually up to five years. At six months, in-stent
LLL was 0.09+/-0.31 mm in the Svelte IDS group compared to 0.13+/-0.27 mm in the
Resolute Integrity group (p<0.001 for non-inferiority). TVF at one year was
similar across the Svelte IDS and Resolute Integrity groups (6.5% vs. 9.8%,
respectively). CONCLUSIONS: DIRECT II demonstrated the non-inferiority of the
Svelte IDS to Resolute Integrity with respect to in-stent LLL at six months.
Clinical outcomes at one year were comparable between the two groups.
PMID- 27497362
TI - Long-term clinical outcomes after percutaneous coronary intervention versus
coronary artery bypass grafting for acute coronary syndrome from the DELTA
registry: a multicentre registry evaluating percutaneous coronary intervention
versus coronary artery bypass grafting for left main treatment.
AB - AIMS: Our aim was to compare, in a large unprotected left main coronary artery
(ULMCA) all-comer registry, the long-term clinical outcome after percutaneous
coronary intervention (PCI) with first-generation drug-eluting stents (DES)
versus coronary artery bypass grafting (CABG) in patients with acute coronary
syndrome (ACS). METHODS AND RESULTS: Of a total of 2,775 patients enrolled in the
Drug Eluting Stents for Left Main Coronary Artery Disease (DELTA) multicentre
registry, 379 (13.7%) patients with ACS treated with PCI (n=272) or CABG (n=107)
were analysed. Baseline demographics were considerably different in the two
groups before propensity matching. No significant differences emerged for the
composite endpoint of all-cause death, myocardial infarction (MI), and
cerebrovascular accident (HR 1.11, 95% CI: 0.63-1.94; p=0.727), all-cause death
(HR 1.26, 95% CI: 0.68-2.32; p=0.462), the composite endpoint of all-cause death
and MI (HR 1.02, 95% CI: 0.56-1.84; p=0.956), and major adverse cardiac and
cerebrovascular events (HR 0.82, 95% CI: 0.50-1.36; p=0.821). However, a higher
incidence of target vessel revascularisation (HR 4.67, 95% CI: 1.33-16.47;
p=0.008) was observed in the PCI compared with the CABG group, which was
confirmed in the propensity score-matched analysis. CONCLUSIONS: In the DELTA all
comer, multinational registry, PCI for ACS in ULMCA is associated with comparable
clinical outcomes to those observed with CABG at long-term follow-up, despite the
use of first-generation DES.
PMID- 27497363
TI - Rotational atherectomy of undilatable coronary stents: stentablation, a clinical
perspective and recommendation.
AB - AIMS: Our aim was to examine procedural viability and midterm outcomes following
the use of rotational atherectomy (RA) on malapposed, crippled, otherwise non
salvageable metallic stents (i.e., stentablation [SA]), and convey important
procedural pointers for practitioners encountering such situations. METHODS AND
RESULTS: Data on twelve SA subjects were analysed. The primary endpoint was
procedural success: effective ablation of the malapposed stent and successful
implantation of a new device. Major adverse cardiac events (MACE) and all-cause
death at six months following the index procedure were examined as a secondary
endpoint. All twelve patients underwent successful SA and novel stent
implantation, with sufficient salvage of coronary anatomy (residual stenosis
<30%). At six-month follow-up, however, MACE amounted to 50% and all-cause
mortality to 25% in the inspected subjects. CONCLUSIONS: We found that, although
feasible as an acute salvage option, SA distinctively increases post-procedural
midterm MACE and mortality rates. This places emphasis on the importance of
avoiding eventual SA situations, underlining the importance of ample lesion
preparation prior to stent implantation.
PMID- 27497364
TI - The clinical impact of vascular complications as defined by VARC-1 vs. VARC-2 in
patients following transcatheter aortic valve implantation.
AB - AIMS: The Valve Academic Research Consortium (VARC) recommendations were devised
to standardise clinical endpoint definitions which best reflect the safety and
efficacy of transcatheter aortic valve implantation (TAVI). The categorisation of
vascular complications (VC) is greatly affected by the definition, but the impact
of its change is unclear. We sought to compare VC between VARC-1 and VARC-2
definitions as a predictor for survival. METHODS AND RESULTS: A series of 376
patients undergoing TAVI by the transfemoral or transapical approach was studied.
We defined VC according to VARC-1 and VARC-2, and compared the mortality one year
after the procedure. Kaplan-Meier curves showed numerically lower survival rates
at one year by major VC with both definitions, but only VARC-2 had statistical
significance: 79.3% vs. 60.7% with VARC-2 (p=0.014), and 78.9% vs. 70.5% with
VARC-1 (p=0.20). Cox regression multivariable models showed major VC with VARC-2
definition to be an independent predictor of mortality (hazard ratio of 3.0, 95%
confidence interval: 1.4-6.6, p=0.006), but not when it was substituted by the
VARC-1 definition (p=0.15). CONCLUSIONS: The VARC-2 definition of VC offers
better predictive value of survival than the VARC-1 definition, supporting its
efficacy as a standard definition.
PMID- 27497365
TI - Early European experience with the Venus P-valve(r): filling the gap in
percutaneous pulmonary valve implantation.
AB - AIMS: Our aim was to report the first five cases of percutaneous implantation of
the Venus P-valve(r) in Europe. METHODS AND RESULTS: We successfully implanted
Venus P-valves in five consecutive cases in patients whose anatomy was thought to
be unfavourable for currently available percutaneous valve prostheses and who had
relative contraindications to surgical valve replacement. The procedures were
performed at Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
The primary diagnosis was variable with variable pulmonary artery morphology. The
median age was 14 years (range 12-62 yrs). There was no mortality and no major
morbidity, with satisfactory haemodynamic and angiographic outcomes in all
patients. Post-procedural follow-up (median follow-up 8.5 months, range three to
15 months) with echocardiography and magnetic resonance imaging showed no
restenosis or regurgitation with significant improvement in the right ventricular
end-diastolic volumes. CONCLUSIONS: Preliminary results show that the Venus P
valve can be safely and efficaciously used in dilated right ventricular outflow
tracts of varying morphology. Rigorous trials will be required to evaluate this
valve before more widespread use.
PMID- 27497366
TI - Transcatheter closure of atrial septal defects without fluoroscopy: a well
established procedure for alternative use in children.
AB - AIMS: The feasibility of transcatheter closure of atrial septal defects (ASD)
without fluoroscopy has been proven. However, the technique has not been accepted
for routine use. We report our experience with trans-catheter closure of ASD
without fluoroscopy and introduce a well-established technique for alternative
use in children. METHODS AND RESULTS: From November 2013 to May 2015, a total of
114 children with isolated secundum ASD (diameter 6 mm to 24 mm, median 13.8 mm)
underwent attempted transcatheter device closure under the guidance of
transoesophageal echocardiography without fluoroscopy. Using a modified delivery
system and procedure technique, ASD were successfully closed in 110 patients
(96.5%, 52 males, 58 females, aged from three to 14 years, median 5.4 years,
weight 12 to 46 kg, median 23.5 kg). Procedure time ranged from eight to 42
minutes (median 18 min). Three patients underwent percardiac device closure after
failed procedures. In the early stage of our study, before delivery system and
technique modification, one patient was converted to open heart surgery due to
rupture of the left appendage. No intervention-related complications were
detected during a median follow-up of nine months. CONCLUSIONS: Using a modified
delivery system and a re-established procedure, we showed that transcatheter
closure of ASD without fluoroscopy is a safe technique for alternative use in
children.
PMID- 27497367
TI - Carotid artery stenting with a new-generation double-mesh stent in three high
volume Italian centres: clinical results of a multidisciplinary approach.
AB - AIMS: Carotid artery stenting (CAS) is still associated with higher
periprocedural cerebrovascular events (CEs) compared to vascular surgery. The
Roadsaver carotid artery stent is a double layer micromesh stent which reduces
plaque prolapse and embolisation by improving plaque coverage. Its clinical
impact on neurological outcome was unknown. The aim of this study was therefore
to report the clinical results of a large real-world population from three
different centres receiving a Roadsaver stent to treat carotid artery disease.
METHODS AND RESULTS: One hundred and fifty (150) patients (age 74+/-8 yrs, 75%
male, symptomatic 29%) treated with CAS using the Roadsaver carotid stent in
three high-volume Italian centres were included in the study. Intraprocedural
optical coherence tomography (OCT) evaluation was performed in 26 patients, with
an off-line analysis by a dedicated core laboratory. All patients underwent
duplex ultrasound and neurological evaluation at 24 hours and at 30 days. CAS was
technically successful in all cases (stent diameter: 8.6+/-0.8 mm, stent length:
25.0+/-4.5 mm). No in-hospital or 30-day CEs were observed. OCT evaluation
detected a low rate of plaque prolapse (two patients, 7.7%). Duplex ultrasound
showed stent and external carotid artery patency in all cases both before
discharge and at 30-day follow-up. CONCLUSIONS: The Roadsaver stent is a safe and
promising technology for CAS, with a low percentage of plaque prolapse and good
short-term clinical outcome. Larger studies with longer follow-up are necessary
to confirm this favourable clinical outcome.
PMID- 27497369
TI - Meta-analysis: don't do what I did.
PMID- 27497368
TI - Invasive aortic pulse wave velocity as a marker for arterial stiffness predicts
outcome of renal sympathetic denervation.
AB - AIMS: A recurrent finding of trials on renal sympathetic denervation is a certain
percentage of non-responders. The aim of this study was to examine the influence
of arterial stiffness to predict response. METHODS AND RESULTS: Eighty-eight
patients were included in the study. Arterial stiffness was measured by invasive
pulse wave velocity. Antihypertensive medication had to be unchanged during
follow-up. Ambulatory blood pressure measurement (ABPM) was used to record blood
pressure before and six months after denervation. Fifty-eight patients without
changes in medication were included in the final analysis. Responders (n=37;
blood pressure reduction -12.8+/-6.4 mmHg) had a significantly lower pulse wave
velocity (14.4+/-4.4 m/s versus 17.7+/-4.5 m/s; p=0.009) compared to non
responders (n=21; blood pressure reduction +3.0+/-4.5 mmHg; p<0.001 for
comparison with responders). In multivariate analysis, invasive pulse wave
velocity was the only significant predictor of blood pressure reduction after
denervation (odds ratio 1.15, 95% confidence interval [CI] 1.014-1.327; p=0.03).
Patients with increased stiffness were older (p=0.001), had a higher prevalence
of diabetes (p=0.008), more often had isolated systolic hypertension (p=0.007),
and had a higher invasive pulse pressure (p<0.001). CONCLUSIONS: Patients with
lower pulse wave velocity showed a significantly better response to denervation.
These findings emphasise that pulse wave velocity might be used as a selection
criterion for renal denervation.
PMID- 27497370
TI - Effects of low-level laser therapy on autogenous bone graft stabilized with a new
heterologous fibrin sealant.
AB - Autogenous bone grafts are used to repair bone defects, and the stabilization is
needed for bone regeneration. Laser photobiomodulation is a modality of treatment
in clinical practice for tissue regeneration, and it has therapeutic effects as
an anti-inflammatory, analgesic and modulating cellular activity. The aim of the
present study was to evaluate the effects of low-level laser therapy (LLLT) on an
autogenous bone graft integration process stabilized with a new heterologous
fibrin sealant. Forty rats were divided into two groups: Autogenous Fibrin Graft
(AFG, n=20), in which a 5mm dome osteotomy was conducted in the right parietal
bone and the graft was adhered to the left side using fibrin sealant; and
Autogenous Fibrin Graft Laser (AFGL, n=20), which was subjected to the same
procedures as AFG with the addition of LLLT. The treatment was performed
immediately following surgery and then three times a week until euthanasia, using
an 830nm laser (30mW, 6J/cm(2), 0.116cm(2), 258.6mW/cm(2), 2.9J). Five animals
from each group were euthanized at 10, 20, 30 and 40days postoperative, and the
samples were submitted to histomorphological and histomorphometric analysis.
Partial bone regeneration occurred, with new bone tissue integrating the graft to
the recipient bed and small areas of connective tissue. Comparative analysis of
the groups at the same intervals revealed minor interfaces in group AFGL, with
statistically significant differences (p<0.05) at all of the analyzed intervals
(10days p=0.0087, 20days p=0.0012, 30days p<0.0001, 40days p=0.0142). In
conclusion, low-level laser therapy stimulated bone regeneration and accelerated
the process of integration of autogenous bone grafts.
PMID- 27497371
TI - Network dynamics in dyslexia: Review and implications for remediation.
AB - Extant neurobiological theories of dyslexia appear fractional in focusing on
isolated brain regions, mechanisms, and functional pathways. A synthesis of
current research shows support for an Interactive Specialization (IS) model of
dyslexia involving the dysfunctional orchestration of a widely-distributed,
attentionally-controlled, hierarchical, and interhemispheric circuit of
intercommunicating neuronal networks. This circuitry is comprised principally of
the frontostriatal-parietal cognitive control system of networks, the posterior
corpus callosum, and the left arcuate fasciculus. During development, the
coalescence of these functionally specialized regions, acting together, may be
essential to preventing the core phonemic and phonological processing deficits
defining the dyslexic phenotype. Research demonstrating an association of each
with processing phonology presents the foundational outline for a comprehensive,
integrative theory of dyslexia and suggests the importance of inclusive remedial
efforts aimed at promoting interactions among all three networking territories.
PMID- 27497372
TI - Aiding the diagnosis of AD/HD in childhood: Using actigraphy and a continuous
performance test to objectively quantify symptoms.
AB - The current gold standard for the diagnosis of AD/HD is based on subjective
reports from teachers, parents, and clinicians. These measures can be problematic
as they are open to rater biases and also fail to account for the developmental
nature of symptoms. The current study examined the diagnostic accuracy of two
objective measures, a computer-based Continuous Performance Task and actigraphy
(e.g. motion tracking device) in differentiating children with AD/HD (N=70) from
healthy controls (N=70). It was predicted that task-unrelated movement (measured
via actigraphy) during a CPT and CPT performance would have high classification
accuracy in differentiating children with AD/HD from healthy controls, and that
the inclusion of age would increase this accuracy. Results indicated that total
energy expenditure from the task-unrelated wrist and ankle movement during the
CPT was higher in children with AD/HD than controls, and that CPT performance was
poorer in AD/HD than controls. Discriminant function analyses revealed that the
CPT Full-Scale Response Control Quotient and wrist and ankle energy expenditure
provided optimal classification accuracy - correctly classifying 86% of cases,
with sensitivity of 81.4% and specificity of 91.4%. The prediction that
classification accuracy would increase with the inclusion of age was not
supported by the data. When taken in conjunction with other clinical assessments,
these findings suggest that actigraphy during a CPT and CPT performance may
increase the probability of a correct AD/HD diagnosis.
PMID- 27497373
TI - Mental health and positive change among Japanese mothers of children with
intellectual disabilities: Roles of sense of coherence and social capital.
AB - We investigated predictors of mental health and positive change among mothers of
children with intellectual disabilities in Japan based on the concept of the
Double ABCX model. We used variables of having a child with autism spectrum
disorder (ASD) and dissatisfaction with systems as stressors, availability of
social support and social capital (SC) as existing resources, sense of coherence
(SOC) as appraisal of the stressor, and mental health and positive change as
adaptation. A self-administered questionnaire was distributed to 10 intellectual
disability-oriented special needs schools in Tokyo, and obtained 613 responses
from mothers of children under age 20 attending these schools. The results showed
that our Double ABCX model explained 46.0% of the variance in mothers' mental
health and 38.9% of the variance in positive change. The most powerful predictor
of this model was SOC, and SC may be directly and indirectly related to maternal
mental health and positive change through mothers' SOC. Increasing opportunity
for interaction between neighbors and family of children with disabilities may be
one effective way to enhance SOC through SC. Since maternal SOC, SC, mental
health, and positive change were significantly correlated with each other,
synergy among these elements could be expected.
PMID- 27497374
TI - Performance Equivalence and Validation of the Soleris Automated System for
Quantitative Microbial Content Testing Using Pure Suspension Cultures.
AB - Using United States Pharmacopeia-National Formulary (USP-NF) general method
<1223> guidance, the Soleris((r)) automated system and reagents (Nonfermenting
Total Viable Count for bacteria and Direct Yeast and Mold for yeast and mold)
were validated, using a performance equivalence approach, as an alternative to
plate counting for total microbial content analysis using five representative
microbes: Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa,
Candida albicans, and Aspergillus brasiliensis. Detection times (DTs) in the
alternative automated system were linearly correlated to CFU/sample (R(2) = 0.94
0.97) with >=70% accuracy per USP General Chapter <1223> guidance. The LOD and
LOQ of the automated system were statistically similar to the traditional plate
count method. This system was significantly more precise than plate counting (RSD
1.2-2.9% for DT, 7.8-40.6% for plate counts), was statistically comparable to
plate counting with respect to variations in analyst, vial lots, and instruments,
and was robust when variations in the operating detection thresholds (dTs; +/-2
units) were used. The automated system produced accurate results, was more
precise and less labor-intensive, and met or exceeded criteria for a valid
alternative quantitative method, consistent with USP-NF general method <1223>
guidance.
PMID- 27497375
TI - Dual-energy computed tomographic imaging of pulmonary hypertension.
AB - Dual-energy computed tomography (DECT) angiography of the chest provides a
combined morphological and functional analysis of the lung, usually obtained in a
single acquisition without extra radiation or injection of extra intravenous
iodine contrast. The parenchymal iodine maps generated by DECT are well
correlated with scintigraphy, and are becoming an essential tool for evaluating
patients with pulmonary vascular diseases. With a single DECT acquisition,
complete imaging of pulmonary hypertension is now available, displaying vascular
anatomy, parenchymal morphology and functional assessment. Triangular pulmonary
perfusion defects in chronic thromboembolic pulmonary hypertension may be clearly
analysed even in the presence of distal arterial occlusion. Perfusion
heterogeneities seen in patients with pulmonary arterial hypertension reflect
mosaic perfusion and may be helpful for the diagnosis, severity assessment and
prognosis of the disease. Vascular or parenchymal abnormalities can also be
analysed with perfusion defects to determine their aetiology. Pulmonary arterial
hypertension due to congenital heart disease can be assessed with a single DECT,
even in the neonatal population. Furthermore, new applications are emerging with
ventilation imaging or myocardial perfusion imaging obtained by DECT and should
be considered. In conclusion, DECT of the thorax enables the simultaneous and
noninvasive assessment of vascular anatomy, parenchymal morphology and functional
pulmonary imaging in various groups of PH.
PMID- 27497377
TI - Indian survey on practice patterns of lacrimal and eyelid disorders (iSUPPLE)
report 1: Congenital nasolacrimal duct obstruction.
AB - BACKGROUND: To assess the preferred practice patterns in the management of
congenital nasolacrimal duct obstruction (CNLDO) among oculoplastic surgeons in
India. The survey was aimed at obtaining data on the timing of intervention,
procedure of choice, and the use of adjunctive techniques such as silicone
intubation and nasal endoscopy. METHODS: An anonymized survey that included
questions on the management of lacrimal disorders was sent in April 2015 to
members of the Oculoplastic Association of India (OPAI), through an e-mail
communication. The results were tabulated and analyzed. RESULTS: A large
proportion (84%) of respondents indicated that they advise lacrimal sac
compression up to 1 year of age. Fourteen percent (12/87) indicated 2 years as
their upper age limit for advising sac compression. One year is the preferred
minimum age for advising primary nasolacrimal duct (NLD) probing by majority
(45%) of respondents and the upper age limit being 5 years for 62% of
respondents. Based on experience, younger surgeons (<10 years experience) when
compared to more experienced surgeons are more likely to offer a trial of primary
probing in children between 8 and 12 years age (29% versus 8%). Nasal endoscope
is used by 50% (44/88) respondents during primary NLD probing. Nearly a third of
the respondents (29/88) use intubation in all cases of NLD probing. Eighty one
percent (71/88) of the surgeons would rather repeat NLD probing with adjunctive
procedures over dacryocystorhinostomy (17%). Balloon Dacryoplasty is rarely used
for CNLDO amongst our respondents. CONCLUSIONS: This study highlights the
variation in practice pattern in the management of CNLDO across India. While
there are certain trends that are global phenomena, such as the shift towards the
use of a nasal endoscope; use of silicone intubation in repeated procedures and
time of performing primary NLD probing; issues like the use of balloon
dacryoplasty showed lesser degree of agreement.
PMID- 27497376
TI - Pediatric malignant salivary gland tumors: 60 year follow up.
AB - OBJECTIVE: To evaluate the presentation, treatments and outcomes in pediatric
patients with salivary gland malignancies. STUDY DESIGN: Retrospective chart
review (1950-2012), Prospective phone interview. METHODS: Patients <=18 years old
with a salivary gland malignancy treated at our institution were identified.
Patients were also contacted by phone for a follow up survey. RESULTS: Fifty-six
patients were identified. Tumor origin was 88% parotid (n = 49), 5% (n = 3)
submandibular and 7% (n = 4) minor salivary glands. Time from onset of symptoms
to diagnosis was over one year (mean = 14.4 years). Fifteen out of 52 patients
with major gland malignancy had a locoregional recurrence and local recurrences
were almost all after initial enucleation. Two of these patients died of disease
(overall disease specific survival = 96%). Three out of 4 patients with minor
gland malignancy had a local recurrence and two patients with high grade
pathology developed metastases and died of their disease (overall survival =
50%). On long term follow up survey in 13 patients (25%), 100% reported normal
facial movement and 54% described symptoms of Frey's syndrome, which is higher
than other reported series in children. Recurrence was noted up to 45 years after
initial treatment. CONCLUSIONS: The majority of malignant pediatric salivary
gland tumors are low grade and have excellent survival, especially if found at an
early stage. Minor salivary gland malignancies, particularly high grade, have a
worse prognosis. Long term mild Frey's syndrome can be expected in approximately
half of patients. We advocate a need for long term follow up and increased
awareness among providers to diagnose these patients earlier.
PMID- 27497378
TI - Management of posterior ankyloglossia and upper lip ties in a tertiary
otolaryngology outpatient clinic.
AB - OBJECTIVES: Recent studies have shown an association between ankyloglossia
(tongue tie) and upper-lip ties to breastfeeding difficulties. Treatment is
commonly multidisciplinary involving lactation consultants and surgical
management with tongue tie and upper lip tie release. There is currently limited
data looking at posterior ankyloglossia and upper lip ties. METHODS: Consecutive
patients seen at an ENT outpatient clinic for ankyloglossia and upper-lip ties
from May 2014-August 2015 were assessed for an outpatient frenotomy.
Breastfeeding outcomes were assessed following the procedure. RESULTS: 43 babies
were seen and 34 patients had a procedure carried out. Babies ranged from 2 to 20
weeks old with the median age being 6.6 weeks. The most common presenting
complaint was latching issues (85%) with mothers' painful nipples being the
second (65%). 21 patients (62%) had a tongue tie release, 10 (29%) had both a
tongue tie and upper lip tie divided, whereas 3 (9%) had an upper-lip tie alone
divided. 29 (85%) of the patients who had a procedure carried out had an
immediate improvement in breastfeeding, while 28 (82%) had a continued
improvement at 2 weeks follow up. CONCLUSIONS: Frenotomy for posterior
ankyloglossia and upper lip ties is a simple procedure that can be carried out in
an outpatient setting with apparent immediate benefit. Otolaryngologists are
likely to have an increasing role to play in the evaluation and management of
ankyloglossia and upper lip ties in babies with breastfeeding difficulties.
PMID- 27497379
TI - Individual-level effects of antibiotics on colonizing otitis pathogens in the
nasopharynx.
AB - BACKGROUND: Although there is evidence of an association between antibiotic
consumption and resistant bacteria on a population level, the relationship on an
individual level has been less well studied, particularly in terms of
nasopharyngeal colonization. We have therefore analysed this association, using
data from a closely followed cohort of children taking part in a vaccination
trial. METHODS: 109 children with early onset of acute otitis media (AOM) were
randomised to heptavalent pneumococcal conjugate vaccine (PCV7) or no
vaccination. They were followed for three years with scheduled appointments as
well as sick visits. Nasopharyngeal cultures were obtained at all visits.
Antibiotic treatments were recorded, as were risk factors for AOM, including
siblings, short breast-feeding and parental smoking. Data were entered into a Cox
regression model, and the findings of Streptococcus pneumoniae and Haemophilus
influenzae with reduced susceptibility to the penicillin group were related to
the number of previous courses of antibiotics. RESULTS: There was evidence of an
association between the amount of previously consumed betalactams and
colonization with beta-lactamasenegative ampicillin-resistant (BLNAR) H.
influenzae (RR 1.21; 95% CI 1.03-1.43; p = 0.03), and also with the most commonly
prescribed drug; amoxicillin (RR 1.39; 95% CI 1.09-1.76; p = 0.01). There was no
evidence for an association between antibiotic consumption and betalactamase
producing H. influenzae or S. pneumoniae with reduced susceptibility to
penicillin. Furthermore, there was no evidence of an association between
resistant bacteria and AOM risk factors or PCV7. CONCLUSION: In this subgroup of
children, most of whom were given several courses of antibiotics in early
childhood, there was evidence of an association between betalactam/amoxicillin
consumption and nasopharyngeal colonization with BLNAR strains, bacteria that
have increased in prevalence during the last 10-15 years, and that are
notoriously difficult to treat with oral antibiotics.
PMID- 27497380
TI - Radiologically-guided balloon sialoplasty for treatment of salivary duct
stricture: A novel technique in young children.
AB - OBJECTIVES: To describe our experience using radiologically-guided balloon
sialoplasty to successfully treat sialadenitis in two children as a single
modality intervention. METHODS: A retrospective case series. RESULTS: Both
children were successfully treated using balloon sialoplasty with complete and
lasting resolution of their symptoms. CONCLUSION: Paediatric sialadenitis
secondary to salivary strictures are traditionally managed surgically. We believe
that this is the first article to describe this intervention in such a series of
children and that balloon sialoplasty is a safe technique and can be repeated as
necessary, which should be considered as a management option in such paediatric
cases.
PMID- 27497381
TI - Follow-up care after grommet insertion in children: Review article.
AB - BACKGROUND: Grommet insertion is a common procedure in children. A lengthy
otolaryngology follow-up can have an adverse impact on clinic waiting times, new
patient appointment availability, and pecuniary disadvantage for the hospital.
OBJECTIVE OF REVIEW: To consolidate research and opinion concerning follow-up
care following grommet insertion in a pediatric population. SEARCH STRATEGY: The
literature between January 1990 and September 2015 was searched on MEDLINE
(Ovid), Google Scholar, PubMed and Web of Science databases. RESULTS: Guidelines
and consensus of opinion from the United States advocate that an initial post
operative review should take place within 4 weeks, and subsequent appointments
every 6 months until grommet extrusion. Recent audit reports from the United
Kingdom have shown that some groups arrange their first post-operative review at
3 months, and subsequent appointments vary considerably from no further follow-up
to up to 24 months. Up to 75% of follow-up appointments were scheduled despite
normal audiometry and clinical findings after grommet insertion, suggesting a
large cohort of patients may undergo unnecessary specialist clinic reviews.
General practioners (GP), audiologists or specialist nurses are potential
alternative providers of regular reviews to ensure normal hearing thresholds and
an adequate tympanic membrane healing course. CONCLUSION: Follow-up schedules are
largely driven by consensus of opinion. A significant number of follow-up
appointments in otolaryngology clinic appear to be redundant. Recently attention
has been drawn to earlier discharge from otolaryngology clinic with subsequent
follow-up in less resource and cost intensive clinics coordinated by GPs,
audiologist or nurses, which may help alleviate some outpatient workload on acute
hospital trusts.
PMID- 27497382
TI - Preliminary results of video Head Impulse Testing (vHIT) in children with
cochlear implants.
AB - OBJECTIVE: To evaluate the lateral semicircular canal high frequency vestibulo
oculomotor reflex (LSC HF VOR) in children with cochlear implant. METHODS: 16
children (10 females and 6 males, age range = 5-17 years) receiving a unilateral
(n = 12) or a bilateral (n = 4) cochlear implant were included and compared to a
control group of 20 age-matched normal-hearing (NH) children. Both implanted and
NH children received a vestibular function test battery, including a Vestibulo
Ocular Reflex (VOR) gain assessment by means of a video-Head Impulse Test (vHIT),
which represented the main outcome measure. In implanted subjects, vHIT was
measured on both sides in the "CI-ON" and "CI-OFF" conditions. RESULTS: Overall,
no significant LSC HF VOR gain difference was found between CI users and NH
peers. In the unilaterally implanted group, the LSC HF VOR gain measured in the
"CI-ON" condition was significantly higher than in the "CI-OFF" condition, both
in the implanted and in the non-implanted ear. In the bilaterally implanted group
there was no such a difference between the two conditions, on either side.
CONCLUSION: This is the first study investigating the LSC HF VOR gain in children
with unilateral and bilateral CI. The study demonstrates that the LSC HF VOR of
bilaterally implanted children is comparable to normal hearing children.
PMID- 27497383
TI - Speech outcomes in children with 22q11.2 deletion syndrome following surgery for
velopharyngeal insufficiency.
AB - OBJECTIVE: The purpose of this study was to identify prognostic factors
associated with improved speech outcomes following surgical correction for
velopharyngeal insufficiency (VPI) in pediatric patients with 22q11.2 deletion
syndrome (22q11DS). METHODS: Eighteen patients were identified via retrospective
chart review of patients with 22q11DS between 2005 and 2014. Patient
characteristics, medical histories, associated comorbidities, surgical
procedures, and pre- and postoperative perceptual hypernasality (subjectively
rated 1-5 with 5 being the most severe) were gathered for each patient. RESULTS:
12 patients (67%) experienced improvement in hypernasality following corrective
surgery for VPI. Higher severity of hypernasality preoperatively was found to be
indicative of a lower chance of improvement with VPI surgery. Of 8 patients with
a preoperative hypernasality score of 5, 3 (38%) showed improvement in
hypernasality postoperatively, while 9 out of 10 (90%) of patients with a
preoperative hypernasality score less than 5 showed postoperative improvement.
Females were also found to have worse speech outcomes compared to males.
CONCLUSION: 22q11DS patients presenting with severely hypernasal speech
preoperatively are less likely to show improvement in hypernasality following
corrective surgery for VPI. Those patients with moderate hypernasality are most
likely to benefit from surgery.
PMID- 27497384
TI - Pediatric head and neck injuries due to golf cart trauma.
AB - INTRODUCTION: Golf carts are increasingly used off the golf course and are often
viewed as innocuous modes of transportation. However, research has shown they can
cause significant injuries, particularly to children. OBJECTIVES: Analyze golf
cart related head and neck injuries in children and adults from a national
database. METHODS: The National Electronic Injury Surveillance System (NEISS) was
queried for golf cart injuries. The NEISS tracks consumer product related
injuries from a sampling of approximately 100 emergency departments across the
United States. Age, general diagnosis (concussion, fracture, laceration), body
part injured, disposition (hospitalized, discharged), location injury occurred,
and mechanism of injury were analyzed. RESULTS: Over an 11-year period, a total
of 3433 total patients were identified. There were 1471 children (16 years old or
younger), which compromised 42.9% of the cohort. Children were injured at home or
on the road 44.7% of the time compared to only 16.6% of adults (p < 0.003).
Children injured their head or neck 42.6% of the time compared to 28.6% of adults
(p < 0.0001). Adults who were hit by a car while riding a golf cart or were
ejected from the golf cart 44.6% of the time compared to 61.7% of children (p <
0.0001). There were 3.9% of children with a face, head, or neck fracture compared
to only 2.4% of adults (p = 0.01). CONCLUSION: Children are more vulnerable to
golf cart related injuries, specifically to the head and neck.
PMID- 27497385
TI - Quality improvement utilizing in-situ simulation for a dual-hospital pediatric
code response team.
AB - OBJECTIVE: Given the rarity of in-hospital pediatric emergency events,
identification of gaps and inefficiencies in the code response can be difficult.
In-situ, simulation-based medical education programs can identify unrecognized
systems-based challenges. We hypothesized that developing an in-situ, simulation
based pediatric emergency response program would identify latent inefficiencies
in a complex, dual-hospital pediatric code response system and allow rapid
intervention testing to improve performance before implementation at an
institutional level. METHODS: Pediatric leadership from two hospitals with a
shared pediatric code response team employed the Institute for Healthcare
Improvement's (IHI) Breakthrough Model for Collaborative Improvement to design a
program consisting of Plan-Do-Study-Act cycles occurring in a simulated
environment. The objectives of the program were to 1) identify inefficiencies in
our pediatric code response; 2) correlate to current workflow; 3) employ an
iterative process to test quality improvement interventions in a safe
environment; and 4) measure performance before actual implementation at the
institutional level. RESULTS: Twelve dual-hospital, in-situ, simulated, pediatric
emergencies occurred over one year. The initial simulated event allowed
identification of inefficiencies including delayed provider response, delayed
initiation of cardiopulmonary resuscitation (CPR), and delayed vascular access.
These gaps were linked to process issues including unreliable code pager
activation, slow elevator response, and lack of responder familiarity with layout
and contents of code cart. From first to last simulation with multiple simulated
process improvements, code response time for secondary providers coming from the
second hospital decreased from 29 to 7 min, time to CPR initiation decreased from
90 to 15 s, and vascular access obtainment decreased from 15 to 3 min. Some of
these simulated process improvements were adopted into the institutional response
while others continue to be trended over time for evidence that observed changes
represent a true new state of control. CONCLUSIONS: Utilizing the IHI's
Breakthrough Model, we developed a simulation-based program to 1) successfully
identify gaps and inefficiencies in a complex, dual-hospital, pediatric code
response system and 2) provide an environment in which to safely test quality
improvement interventions before institutional dissemination.
PMID- 27497387
TI - The effect of Nigella sativa oil on prevention of myringosclerosis in a Guinea
pig model.
AB - OBJECTIVES: In this study, our aim was to identify the possible effects of
Nigella sativa L. (NS) [blackcumin] seed oil on the prevention of experimentally
induced myringosclerosis (MS). MATERIALS AND METHODS: Fourteen Guinea pigs were
used and they were divided into three groups. Tympanic membranes (TM) of all
animals were perforated and then group I was treated with saline soaked gel foams
as a control group, group II was treated with 0.5 ml NS oil soaked gel foams at
0, 24 and 48 h and group III was treated with 5 ml NS oil orally at 0, 24, 48, 72
and 120 h. After 15 days, all animals were euthanized. Tympanic membranes were
evaluated macroscopically and histopathologically. RESULTS: Groups I showed
extensive myringosclerosis in contrast to those of Groups II and III which had
significantly less changes (p < 0.05). The fibrosis and inflammation in the
lamina propria of the tympanic membranes of Groups I was found to be
significantly more pronounced (p < 0.05). The tympanic membranes were found to be
significantly thinner in Groups II and III when compared with Groups I (p <
0.05). CONCLUSIONS: The results of this study suggested that topical or oral
administration of NS oil supressed the inflammation and fibroblastic activity in
the lamina propria of the myringotomized TMs of the Guinea pigs. For providing
further evidence to use plant extracts as antioxidant and antiinflammatory
therapy after myringotomy or ventilation tube insertion, further clinical studies
with larger population will be essential.
PMID- 27497386
TI - An objective assessment of halitosis in children with adenoid vegetation during
pre- and post-operative period.
AB - OBJECTIVES: Although most specialists in otorhinolaryngology and pediatrics find
halitosis to be a common problem in children with adenoid hypertrophy, there are
no objective data on this topic in the literature. Whether adenoid hypertrophy is
a risk factor for halitosis or whether halitosis is a sign of adenoid hypertrophy
remains unclear. Thus, the aim of this study was to investigate whether children
diagnosed with adenoid hypertrophy have a higher probability of halitosis than do
children in the normal population and whether adenoidectomy can decrease oral
malodor. METHODS: Forty children with adenoid hypertrophy and 40 healthy subjects
aged 5-15 years were included in the study. The children with adenoid hypertrophy
underwent adenoidectomy operations and were followed for 3 months. We measured
volatile sulfur compounds (VSCs), hydrogen sulfide (H2S), methyl mercaptan
(CH3SH), and dimethyl sulfide (CH3)2S using an objective method, a portable gas
chromatograph (OralChroma; AbiMedical, Osaka, Japan). RESULTS: The mean CH3SH and
(CH3)2S levels were significantly different (p < 0.05) between the adenoid
hypertrophy group and the controls. The H2S, CH3SH, and (CH3)2S levels in the
third postoperative month were significantly lower (p < 0.05) than those in the
preoperative period, and there was no significant difference postoperatively
between the patients with adenoid hypertrophy and controls. There was a positive
correlation between age and VSC levels, and CH3SH levels were significantly
higher in patients with ventilation tube insertion, rather than just
adenoidectomy. CONCLUSIONS: There was a statistically significant association
between halitosis and adenoid hypertrophy, and a significant improvement in
halitosis was obtained following adenoidectomy. The present study provides an
association between halitosis and adenoid hypertrophy. If there is no other oral
pathology causing halitosis, halitosis can be a sign of adenoid hypertrophy in
children.
PMID- 27497388
TI - A study of cell proliferation using immunohistological staining: A case report of
congenital granular cell epulis.
AB - An unusual case of a 1-day-old Chinese female neonate with a solid tumor mass in
the maxillary anterior ridge of the edentulous jaw is reported. Based on the
clinical and histopathological features, the diagnosis was of obstructive
congenital granular cell epulis (CGCE) which is an uncommon benign tumor that
preferentially develops in female infants. Immunohistochemical analysis of the
lesion was performed and the rate of cell proliferation was determined by
immunostaining with Ki-67 and PCNA, which showed labeling indexes of 11.1% and
33.3%, respectively. No recurrence was observed in the follow-up.
PMID- 27497389
TI - Management of unilateral hearing loss.
AB - OBJECTIVE: A representative sample of literature regarding unilateral hearing
loss (UHL) was reviewed to provide evidence of the effects of UHL and the
intervention options available for children with UHL. Considerations during the
assessment and management of children with UHL are illustrated using case
illustrations. METHOD: Research articles published from 2013 to 2015 were
searched in the PubMed database using the keywords "unilateral hearing loss".
Articles from 1950 to 2013 were included from a previous literature review on
minimal hearing loss [1]. A retrospective review of charts of 14 children with
UHL was also conducted. RESULTS: The evidence indicates that children with UHL
are more likely to have structural anomalies of the inner ear; may face
challenges in six different domains, and have six intervention options available.
Evidence also indicates that although some children appear to exhibit no delays
or difficulties, others have significant challenges, some of which continue into
adulthood. CONCLUSIONS: Children with UHL have to be treated on a case-by-case
basis. Parent education regarding UHL, its effects, and all available management
options is critical so they can make informed decisions. Close monitoring and
good communication between professionals in different domains is crucial in order
to minimize the potential negative effects of UHL.
PMID- 27497390
TI - Morphological changes in the round window membrane associated with Haemophilus
influenzae-induced acute otitis media in the chinchilla.
AB - OBJECTIVE: The round window membrane (RWM) encloses the round window, the opening
into the scala tympani (ST) from the middle ear. During the course of acute
otitis media (AOM), structural changes of the RWM can occur that potentially
affect sound transmission into and out of the cochlea. The relationship between
such structural changes and conductive hearing loss during AOM has remained
unclear. The focus of the current study was to compare the thickness distribution
across the RWM surface between normal ears and those with AOM in the chinchilla.
We assessed the occurrence of AOM-associated histological changes in this
membrane compared to uninfected control animals after AOM of two relatively short
durations. MATERIAL AND METHODS: AOM was induced by transbullar injection of the
nontypeable Haemophilus influenzae strain 86-028NP into two groups of adult
chinchillas (n = 3 each). Bullae were obtained from the two infected groups, at 4
days or 8 days post challenge. Structures and thickness of these RWMs were
compared between the two infected treatment groups and to RWMs from uninfected
control animals (n = 3) at seven different RWM locations. RESULTS: RWM thickness
in infected chinchillas increased significantly at locations along the central
line on the 4th day post bacterial challenge compared to values found for
uninfected control animals. Lymphocyte infiltration and edema were the primary
contributors to these thickness increases. No significant further increases in
RWM thickness were observed when RWMs from chinchillas ears infected for 4 and 8
days were compared. Thickness and structural changes at the RWM lateral and
medial areas were less visually obvious and not statistically significant among
the three treatment groups. These latter RWM regions clearly were less affected
during AOM than the central areas. CONCLUSIONS: This histological study
establishes that H. influenzae-induced AOM causes significant acute changes in
chinchilla RWM structure that are characterized by region-specific increases in
thickness. Our new morphological findings comparing normal and diseased
chinchilla RWMs identify yet another biomechanical mechanism by which nontypeable
H. influenzae may contribute to hearing loss in AOM.
PMID- 27497391
TI - Should obtaining a preoperative audiogram before tympanostomy tube placement be
used as a quality metric? A survey of pediatric otolaryngologists.
AB - INTRODUCTION: Obtaining a preoperative audiogram prior to tympanostomy tube
placement is recommended by the American Academy of Otolaryngology-Head and Neck
Surgery clinical practice guideline (CPG): Tympanostomy tubes in Children, and
this process measure is also used as a quality metric by payers. However, whether
audiograms should be mandated in cases of tube placement for both chronic otitis
media with effusion (COME) and recurrent acute otitis media (RAOM) is
controversial. The objective of this study is to determine reports of practice
patterns of pediatric otolaryngologists regarding obtaining audiograms before and
after tympanostomy tube placement and opinions regarding utility of CPGs and use
of this process measure as a quality metric. METHODS: A 16-question cross
sectional survey of American Society of Pediatric Otolaryngology (ASPO) members
was conducted. Per ASPO policy, no repeated requests or other enhanced response
techniques were permitted. Independent t-tests for proportions were used to
compare responses. RESULTS: 127 pediatric otolaryngologists completed the survey
(response rate 26.9%). Nearly 70% of respondents reported being in practice for
>10 years. 74% of respondents reported obtaining preoperative audiograms "always"
or "most of the time" for COME, vs. 56.7% for RAOM (p < 0.0001). 76% agreed that
obtaining a preoperative audiogram was representative of high quality for COME,
vs. 52% for RAOM (p < 0.0001). 12% of respondents "completely agreed" that
compliance with all aspects of CPGs represented high quality, while 68.8%
responded that they somewhat agreed. CONCLUSION: There is no consensus among
pediatric otolaryngologists regarding the necessity of a preoperative audiogram
in tympanostomy tube placement, especially for RAOM. Further evidence
demonstrating the benefit of preoperative audiogram obtainment should be
developed prior to inclusion as a guideline recommendation and as a quality
metric.
PMID- 27497392
TI - Paroxysmal vertigo with nystagmus in children.
AB - INTRODUCTION: A pathological nystagmus is an objective sign that a patient feels
vertigo. However, there have been few opportunities to observe and record
pathological nystagmus during a paroxysmal vertigo attack. Furthermore, it can be
difficult to obtain cooperation in pediatric patients. We present two cases of
paroxysmal vertigo in children in whom we successfully recorded and analyzed
their pathological nystagmus during a vertigo attack. METHODS: Of a total sample
of 4349 patients seen at our hospital for dizziness in the last decade, a
retrospective analysis revealed that 68 were children (<15 years old; 1.6%). Of
these 68 children, we successfully identified pathological nystagmus during
paroxysmal vertigo in only two (2.9%). RESULTS: Case 1 was a 4-year-old girl. She
felt vertigo the strongest when her left ear was down in the supine position. We
observed and recorded her nystagmus during a vertigo attack with her mother's
permission. Her positional nystagmus in the supine position was horizontal
persistent apogeotropic nystagmus. Rightward nystagmus in the left-ear-down
supine position was stronger than leftward nystagmus in the right-ear-down supine
position. Therefore, the diagnosis was right lateral canal type of benign
paroxysmal positional vertigo, of which the pathophysiology was cupulolithiasis.
The other patient was an 11-year-old boy. He had a family history of migraines.
His vertigo attacks occurred after onset of a severe migraine and lasted between
2 and 48 h. During an attack that we observed, he showed nystagmus, which was
direction-fixed right torsional and rightward in darkness. His mother had noticed
that his eyes moved abnormally and that his left eye did not shift to the left
side when he looked leftward. He was old enough to clearly express his own
symptoms. Other neurological examinations were normal. The diagnosis was
vestibular migraine. CONCLUSIONS: We analyzed a pathological nystagmus during
paroxysmal vertigo in two children. We conclude that children can be diagnosed
with a combination of careful history taking and accurate examinations of a
pathological nystagmus.
PMID- 27497393
TI - Factors contributing to hearing impairment in patients with cleft lip/palate in
Malaysia: A prospective study of 346 ears.
AB - OBJECTIVE: To determine the factors contributing towards hearing impairment in
patients with cleft lip/palate. METHOD: A prospective analysis was conducted on
173 patients (346 ears) with cleft lip and palate (CL/P) who presented to the
combined cleft clinic at University Malaya Medical Centre (UMMC) over 12 months.
The patients' hearing status was determined using otoacoustic emission (OAE),
pure tone audiometry (PTA) and auditory brainstem response (ABR). These results
were analysed against several parameters, which included age, gender, race, types
of cleft pathology, impact and timing of repair surgery. RESULTS: The patients'
age ranged from 1-26 years old. They comprised 30% with unilateral cleft lip and
palate (UCLP), 28% with bilateral cleft lip and palate (BCLP), 28% with isolated
cleft palate (ICP) and 14% with isolated cleft lip (ICL). Majority of the
patients (68.2%) had normal otoscopic findings. Out of the 346 ears, 241 ears
(70%) ears had passed the hearing tests. There was no significant relationship
between patients' gender and ethnicity with their hearing status. The types of
cleft pathology significantly influenced the outcome of PTA and ABR screening
results (p < 0.001). There was no significant difference between the repaired and
unrepaired cleft groups and the outcome of hearing tests. However, hearing
improvement occurred when palatal repair was performed at the age of <1year old
(OR = 2.37, CI 1.2 = 4.6, p = 0.01). CONCLUSION: Majority of the cleft patients
had normal hearing (70%). Hearing threshold varied significantly between the
different types of cleft pathology. Surgery conferred no significant impact on
the hearing outcome unless surgery was performed at the age of <1 year old.
PMID- 27497394
TI - Do race/ethnicity or socioeconomic status affect why we place ear tubes in
children?
AB - INTRODUCTION: Despite recent concerns about potential overuse of tympanostomy
tube (TT) placement to treat otitis media in children, utilization of this common
procedure in the U.S. has been shown to be relatively less common among minority
children. It is not known if the indications for TT differ by child
race/ethnicity and/or socioeconomic status (SES). Our objective is to analyze the
association of patient- and neighborhood-level demographics and SES with clinical
indications for TT. METHODS: We conducted a retrospective chart review of
children who underwent TT at single urban academic tertiary pediatric care center
in a 6-month period (8/2013-3/2014). Children with congenital anomalies or
syndromic diagnoses were excluded (50/137 children, 36.5%). Children were grouped
by primary TT indication, recurrent acute otitis media (RAOM) or chronic otitis
media with effusion (OME). Group characteristics were compared using t-tests and
chi-square analyses, and logistic regression was performed to assess the
association between demographics and TT indication. RESULTS: 87 children were
included in this analysis (mean age = 2.8 years, 1-6 years). The most common
indication for TT was RAOM (53%), and these children had a mean of 6 AOM
episodes/year. Indications for TT varied significantly by the patient's
neighborhood SES (median neighborhood income $70,969.09-RAOM vs $58, 844.95-OME,
p-value = 0.009). Those undergoing TT for RAOM were less likely to live in a high
poverty neighborhood (OR = 0.36,p-value = 0.02), whereas children who underwent
TT for OME were more likely to live in a high-poverty neighborhood. There was no
significant difference in indication by race/ethnicity or insurance type.
CONCLUSIONS: In this population, TT indications differed by SES. Among children
receiving tubes, those from high poverty areas were more likely than those from
low poverty neighborhoods to receive tubes for the indication of OME as opposed
to RAOM. This finding suggests that concerns for appropriate use of TT in the
setting of RAOM may be specific to a more affluent population. Future prospective
patient-centered research will evaluate cultural and economic influences for
families pursuing TT placement, as well as factors considered by physicians who
make surgical recommendations.
PMID- 27497396
TI - The feasibility of pediatric TORS for lingual thyroglossal duct cyst.
AB - A six-year-old boy who presented with symptoms of obstructive sleep apnea was
found to have a midline tongue mass suspicious for lingual thyroglossal duct cyst
(TGDC). Surgery was scheduled after workup confirmed the presence of functional,
orthotopic thyroid tissue. The surgical robot was used to excise the mass
endoscopically without removing any hyoid. He was extubated at the conclusion of
the case. The child tolerated a soft diet and was discharged after an uneventful
overnight stay in the ICU. Pathology confirmed TGDC. There have been no reported
issues in eleven months of follow-up. Our report adds to the scarce literature on
performing such a surgery in a child and demonstrates that with the correct
circumstances, prompt extubation, discharge, and prolonged remission are
possible.
PMID- 27497395
TI - Association of microRNA 146 with middle ear hyperplasia in pediatric otitis
media.
AB - OBJECTIVE: Toll-like receptor signaling activated by bacterial otitis media
pathogens in the middle ear has been shown to play a key role in OM
susceptibility, pathogenesis and recovery. Recent studies implicate microRNA 146
(miR-146) in regulation of inflammation via negative feedback of toll-like
receptor signaling (TLR) in a wide variety of tissues, however its involvement in
otitis media is unknown. METHODS: Human middle ear epithelial cells were
stimulated with proinflammatory cytokines, interleukin 1 beta or tumor necrosis
factor alpha, for two to twenty-four hours. Middle ear biopsies were collected
from children with otitis media with effusion (n = 20), recurrent otitis media (n
= 9), and control subjects undergoing cochlear implantation (n = 10). miR-146a,
miR-146b expression was assayed by quantitative PCR (qPCR). Expression of miR-146
targets involved in TLR signaling, IRAK1 and TRAF6, was assayed by qPCR in middle
ear biopsies. Middle ear biopsies were cryosectioned and epithelial thickness
measured by a certified pathologist. RESULTS: Proinflammatory cytokines induced
expression of miR-146 in middle ear epithelial cells in vitro. Middle ear miR
146a and miR-146b expression was elevated in otitis media patients relative to
control subjects and correlated with middle ear epithelial thickness. A trend
towards inverse correlation was observed between miR-146 and TRAF6 expression in
the clinical population. CONCLUSIONS: This report is the first to assess miRNA
expression in a clinical population with OM. Findings herein suggest miR-146 may
play a role in OM.
PMID- 27497397
TI - Development and validation of a short version of the Spanish pediatric voice
handicap index (P-VHI-10).
AB - OBJECTIVES: A child's voice is used both as a tool for communication and as a
form of emotional expression. Thus, voice disorders suffered by children have
negative effects on their quality of life, which can be assessed using the
"Pediatric Voice Handicap Index" (P-VHI). This questionnaire is completed by the
parents of dysphonic patients and it has been validated in different languages:
Italian, Korean, Arabic, and Spanish. More recently, the "Children Voice Handicap
Index-10" test (C-VHI-10) was developed and validated, an Italian version reduced
into 10 items that is answered by children themselves. The objective of this
study was to develop and validate a short Spanish version of the P-VHI (P-VHI-10)
and to assess whether it is comparable to the Italian C-VHI-10. MATERIALS AND
METHODS: We conducted a cross-sectional study on 27 patients between 6-15 years
of age. We developed an abbreviated version of the P-VHI that consisted of 10
statements to be answered by parents of children with dysphonia (P-VHI-10). These
statements were based on the 10 items with the highest score in the validated
Spanish version of the P-VHI. In addition, the validated Italian version of C-VHI
10 was translated into Spanish and this translation was reviewed and modified by
three specialists, resulting in an adapted version to be answered by parents (C*
VHI-10). The parents and children included in the study of this index were the
same patients as those included in the study to validate the Spanish P-VHI.
RESULTS: There were no significant differences in the results obtained with the
extended version of the P-VHI (17.4) and with the P-VHI-10 (18.7: Pearson
coefficient = 0.602, p < 0.36). A paired student's t-test identified significant
differences (p < 0.0001) when comparing the P-VHI-10 and C*-VHI-10, both of which
were answered by parents, with average scores of 18.7 and 9.48, respectively.
Both these reduced versions have good internal consistency, with a satisfactory
Cronbach's alpha coefficient (alpha = 0.75 to P-VHI-10 and alpha = 0.73 in C*-VHI
10). No statistically significant differences were found when the average total
score between the C-VHI-10 and C*-VHI-10 were compared, with a Pearson's
correlation coefficient of 0.559 (p < 0.9). CONCLUSION: The short version of the
P-VHI10 questionnaire is a clinically valid tool that has good internal
consistency.
PMID- 27497398
TI - Chinese children with nonsyndromic cleft lip/palate: Factors associated with
hearing disorder.
AB - OBJECTIVES: This study examined the auditory status of Chinese children with
nonsyndromic cleft lip/palate (NSCL/P), investigated factors associated with
peripheral hearing loss and compared results with earlier studies in western
countries. METHODS: Case history profiles and audiological data from 148 Chinese
children with NSCL/P, aged between 6 and 15 years, who attended the Cleft Lip and
Palate Clinic Center in a major Chinese urban hospital from July 2012 to
September 2013 were acquired. The audiological status of the participants was
reviewed, based on the results of their pure tone audiometry, tympanometry and
acoustic reflex thresholds assessments. Factors including age, gender, cleft
type, residential locality and school achievement were examined in relation to
auditory status. RESULTS: Findings revealed that 17% of the Chinese children with
NSCL/P had hearing impairment at the time of assessment. Unilateral hearing loss
was noted in 12% of children and in 5% of cases bilateral hearing loss was noted.
In the majority of cases the hearing loss was slight and conductive in nature.
Age, gender, residential locality and school achievement were found to have no
relationship with severity of hearing loss. Children with cleft lip showed a
lower degree of hearing impairment than children with cleft palate or cleft lip
and palate. CONCLUSION: Similar to studies for western children, Chinese children
with CL/P associated with no known syndrome are at risk of peripheral hearing
loss, generally of conductive type. However, the prevalence of peripheral hearing
loss appears to be less than in western children with NSCL/P. Ethnic/racial
factors may be a major contributing factor accounting for the discrepancies
between the current results and western studies.
PMID- 27497399
TI - Chiari malformations: An important cause of pediatric aspiration.
AB - Chronic aspiration poses a major health risk to the pediatric population. We
describe four cases in which work up for chronic aspiration with a brain MRI
revealed a Chiari I malformation, a poorly described etiology of pediatric
aspiration. All patients had at least one non-specific neurologic symptom but had
swallow studies more characteristic of an anatomic than a neurologic etiology.
Patients were referred to neurosurgery and underwent posterior fossa
decompression with symptom improvement. A high index of suspicion for Chiari
malformation should be maintained when the standard work up for aspiration is non
diagnostic, particularly when non-specific neurologic symptoms are present.
PMID- 27497400
TI - To anticoagulate? Controversy in the management of thrombotic complications of
head & neck infections.
AB - OBJECTIVE: To review the thrombotic complications of head and neck infections,
including Lemierre's syndrome, and their management. METHODS: A retrospective
review of pediatric patients presenting to McMaster Children's Hospital from 2009
to 2013 was undertaken. The literature was reviewed for evidence regarding the
use of anticoagulation therapy in this population. RESULTS: Eleven cases (6
males, 5 females) were identified. The median age was 10.9 (range 14 months-17
years). The most frequent head and neck infection causing a thrombotic
complication was mastoiditis (n = 6). All had thrombi identified on imaging, with
the most common location being the sigmoid sinus (n = 6) followed by the internal
jugular vein (n = 5). All 11 patients were anti-coagulated with low molecular
weight heparin (LMWH) within a median of 2 days of diagnosis (average duration
105.8 days). Ten patients (90.9%) had thrombus improvement or resolution within a
median of 3.4 months (range 1.0-13.9). Adverse sequelae from the thrombi were MCA
infarct (n = 1), septic pulmonary emboli (n = 4), cranial nerve palsies (n = 3)
and Horner's syndrome (n = 2). There were no adverse effects from anti
coagulation therapy. Review of the literature revealed anticoagulant use in 63.7%
of pediatric cases reported since 2002. CONCLUSION: Anticoagulation remains
controversial in the management of thrombotic complications from head and neck
infections. Based on this case series, certain recommendations can be made
regarding the benefits of anticoagulation, which appear to outweigh the risks.
Further research is required to establish evidence for consensus in the
antithrombotic management of thrombotic sequelae of head and neck infections.
PMID- 27497401
TI - Evaluation on health-related quality of life in deaf children with cochlear
implant in China.
AB - OBJECTIVE: Previous studies have shown that deaf children benefit considerably
from cochlear implants. These improvements are found in areas such as speech
perception, speech production, and audiology-verbal performance. Despite the
increasing prevalence of cochlear implants in China, few studies have reported on
health-related quality of life in children with cochlear implants. The main
objective of this study was to explore health-related quality of life on children
with cochlear implants in South-west China. STUDY DESIGN: A retrospective
observational study of 213 CI users in Southwest China between 2010 and 2013.
METHODS: Participants were 213 individuals with bilateral severe-to-profound
hearing loss who wore unilateral cochlear implants. The Nijmegen Cochlear Implant
Questionnaire and Health Utility Index Mark III were used pre-implantation and 1
year post-implantation. Additionally, 1-year postoperative scores for Mandarin
speech perception were compared with preoperative scores. RESULTS: Health-related
quality of life improved post-operation with scores on the Nijmegen Cochlear
Implant Questionnaire improving significantly in all subdomains, and the Health
Utility Index 3 showing a significant improvement in the utility score and the
subdomains of ''hearing," ''speech," and "emotion". Additionally, a significant
improvement in speech recognition scores was found. No significant correlation
was found between increased in quality of life and speech perception scores.
CONCLUSION: Health-related quality of life and speech recognition in prelingual
deaf children significantly improved post-operation. The lack of correlation
between quality of life and speech perception suggests that when evaluating
performance post-implantation in prelingual deaf children and adolescents,
measures of both speech perception and quality of life should be used.
PMID- 27497402
TI - Botulinum toxin injections for chronic sialorrhoea in children are effective
regardless of the degree of neurological dysfunction: A single tertiary
institution experience.
AB - OBJECTIVE: To determine the effectiveness of submandibular salivary gland
Botulinum Toxin Type-A (BTX-A) injection in the treatment of drooling in children
with varying degrees of neurological dysfunction. METHODS: A retrospective review
of pre- and post-procedure drooling frequency and severity scores of patients
receiving BTX-A between January 2008 and January 2013. Stratification to
different subgroups of neurological impairment was performed according to Gross
Motor Function Classification System (GMFCS) score. Drooling severity was
assessed using Thomas-Stonell and Greenberg symptom questionnaires administered
at time of initial consultation and 3 months after treatment. RESULTS: 48 sets of
BTX-A injections in 26 patients with an average age of 9.45 years (range 7 months
18 years) were included in the study. Marked improvement in drooling was seen in
60.4% of patients, a marginal or brief improvement was seen in 20.8% and there
was no improvement in 18.8%. No adverse events were reported following any of the
BTX-A injections. BTX-A was safe and effective in the eight patients with pre
existing swallowing dysfunction. Subsequent drooling surgery was performed in 15
(57.7%) of the cohort, all 15 patients responded to BTX-A injections. In patients
with Cerebral Palsy, there was no correlation between the severity of the
neurological dysfunction as measured by the Gross Motor Function Classification
System (GMFCS) score and the response to BTX-A treatment. CONCLUSIONS: Injection
of BTX-A to the submandibular glands of children with neurological disorders is a
safe procedure and results in a reduction in drooling in the majority of
patients. Children with severe neurological dysfunction respond to BTX-A
injections as effectively as their less impaired peers and the degree of response
does not appear to be associated with the severity of neurological disability.
BTX-A injection is a good initial procedure when drooling surgery is being
considered.
PMID- 27497403
TI - Role of group 3 innate lymphoid cells during experimental otitis media in a rat
model.
AB - The objective of this study was to evaluate the role of group 3 innate lymphoid
cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a
rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM),
the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the
tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by
immunohistochemical staining. Immunohistochemical staining of specific cell
surface markers was also assessed to confirm the origin of the cells expressing
IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced
animal model of OM. OM was induced by inoculation of non-typeable Haemophilus
influenzae into the ME cavity of the rats. The rats were divided into four
experimental groups: three infected groups and one control group. Infected groups
were subdivided into sets of 5 rats, one for each of the three time points (1, 4
and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in
infected rats and control rats, infected or control ME mucosa sections were
analyzed by immunohistochemistry with specific antibodies directed against IL-17
and IL-22. Immunohistochemical staining for CD3, RORgammat, and NKp46 were also
conducted on the samples to confirm the origin of cells expressing IL-17 and IL
22. IL-17 and IL-22 serum concentrations were significantly increased in the
infected rats compared to control rats. Immunohistochemical staining revealed
increased IL-17 and IL-22 expressions in all infected ME mucosae from the first
day after inoculation. In addition, the results of tissue staining for the
specific surface markers were negative for CD3 and NKp46, but were highly
positive for RORgammat. IL-17 and IL-22 revealed their association with the
bacterially induced proliferative and hyperplastic responses of ME mucosa, which
are characteristic features in pathogenesis of OM. Surface marker examination
showed that the source cells for IL-17 and IL-22 seemed to be lymphoid tissue
inducer (LTi) cells. The results suggest that LTi cells release IL-17 and IL-22,
and play a significant role in both the early phase of OM induction and recovery
from it.
PMID- 27497404
TI - Lactoferrin gene polymorphisms in Italian patients with recurrent tonsillitis.
AB - INTRODUCTION: Recurrent tonsillitis is an oral pathology characterized by
inflammation of tonsils. The disease susceptibility depends upon environmental
and host factors, specifically the innate immune response, the first line of host
defence could play an important role. Among innate immunity members, lactoferrin,
known for its antimicrobial properties, was previously correlated with the risk
of oral pathology as periodontitis and dental caries. METHODS: 89 Italian
children presenting recurrent tonsillitis and 95 healthy children were genotyped
for two LTF non-synonymous polymorphisms, called Thr29Ala and Arg47Lys, in order
to investigate their potential role in recurrent tonsillitis susceptibility.
RESULTS: no different allele, genotype and haplotype frequency distributions were
detected comparing patients and controls. CONCLUSION: data from the current study
indicate that LTF polymorphisms might not be involved in recurrent tonsillitis
development in our Italian population. However, since the importance of
lactoferrin in oral immunity has been previously assessed, further studies should
be necessary to unravel the potential role of LTF genetic variants in oral
cavity.
PMID- 27497405
TI - Prevention of biofilm formation by polyquaternary polymer.
AB - OBJECTIVE: Biofilm formation has been linked to device-associated infections in
otolaryngology. This study was conducted to determine if a microbicidal
polyquaternary polymer, poly diallyl-dimethylammonium chloride (pDADMAC) could
prevent biofilm development by pathogens that commonly cause implant infections,
Staphylococcus aureus and Pseudomonas aeruginosa. METHODS AND MATERIALS: This
study was prospective and controlled in vitro microbiological study. Polyurethane
tubes (20 per treatment) with and without a polyquaternary polymer coating were
briefly exposed to plasma or saline, then to S. aureus or P. aeruginosa.
Polyurethane tubes were incubated in growth media. After 4 days, antibiotics were
added to kill planktonic bacteria. S. aureus or P. aeruginosa bacterial counts
and scanning electron microscopy (SEM) were performed. RESULTS: S. aureus biofilm
counts were reduced by 8 logs on tubes with polyquaternary polymer coating
compared to the control tubes, either with plasma (3.67E+01 +/- 7.30E+01 vs
1.08E+09 +/- 4.81E+08; P < 0.0001) or without plasma (3.70E+00 +/- 1.10E+01 vs
6.50E+08 +/- 2.79E+08; P < 0.0001). P. aeruginosa biofilm formation was also
reduced on tubes with polyquaternary polymer, either with plasma (2.90E+07 +/-
1.71E+07 vs 9.16E+08 +/- 4.43E+08; P < 0.0001) or without plasma (2.50E+07 +/-
9.54E+06 vs 3.35E+08 +/- 2.18E+08; P < 0.001), but the reduction was only 1 log.
On control tubes, plasma promoted S. aureus (1.08E+09 +/- 4.81E+08 vs 6.05E+08 +/
2.79E+08; P < 0.0001) and P. aeruginosa (9.16E+08 +/- 4.43E+08 vs 3.35E+08 +/-
2.18E+08; P < 0.0001) bacterial counts but not on the tubes coated with
polyquaternary polymer. CONCLUSIONS: Incorporation of the microbicidal
polyquaternary polymer, pDADMAC, into polyurethane dramatically inhibits S.
aureus biofilm formation. Further research is warranted to evaluate the efficacy
and safety of this technology in otolaryngologic implants.
PMID- 27497406
TI - Informed consent for tonsillectomy: Do parents comprehend the information we
provide?
AB - OBJECTIVE: Informed consent is an important part of the surgical process. Based
on our clinical experience, we hypothesized that parents providing consent for
their children's tonsillectomy do not comprehend all the information that is
given to them by the operating surgeon at the time of a conventional consent
process. MATERIALS AND METHODS: Parents whose children were scheduled for
tonsillectomy with or without adenoidectomy and/or tympanostomy tubes insertion
were enrolled. Within one hour after the consent process, they were asked to
complete a questionnaire designed to collect demographic data and to evaluate how
much of the information that was given to them was actually understood. RESULTS:
Ninety-seven parents were enrolled between October 2011 and March 2013. The
average percentage of correct answers (score) for the 16 multiple-choice
questions was 76.3%. The average scores were 84.8% for the native Hebrew-speaking
parents and 71.9% for the parents whose first language was other than Hebrew (p <
0.01). The average scores were 83.3% for the parents who are healthcare system
workers and 74.4% for those parents whose profession is not related to medicine
(p < 0.05). Fifty parents (51.5%) responded incorrectly to at least one of two
questions that we defined as essential: "What would you do if your child starts
to bleed from the mouth" and "What kind of food is recommended for your child
during the first week after the surgery". CONCLUSION: The current conventional
method of obtaining informed consent for tonsillectomy is inadequate, as
reflected by the low level of parental comprehension of essential information.
Further studies which will evaluate methods for improving the consent process are
highly warranted.
PMID- 27497407
TI - Quality of life improvement after pressure equalization tube placement in Down
syndrome: A prospective study.
AB - OBJECTIVE: To evaluate quality-of-life changes after bilateral pressure
equalization tube placement with or without adenoidectomy for the treatment of
chronic otitis media with effusion or recurrent acute otitis media in a pediatric
Down syndrome population compared to controls. STUDY DESIGN: Prospective case
control observational study. METHODS: The OM Outcome Survey (OMO-22) was
administered to both patients with Down syndrome and controls before bilateral
tube placement with or without adenoidectomy and at an average of 6-7 months
postoperatively. Thirty-one patients with Down syndrome and 34 controls were
recruited. Both pre-operative and post-operative between-group and within-group
score comparisons were conducted for the Physical, Hearing/Balance, Speech,
Emotional, and Social domains of the OMO-22. RESULTS: Both groups experienced
improvement of mean symptom scores post-operatively. Patients with Down syndrome
reported significant post-operative improvement in mean Physical and Hearing
domain item scores while control patients reported significant improvement in
Physical, Hearing, and Emotional domain item scores. All four symptom scores in
the Speech domain, both pre-operatively and post-operatively, were significantly
worse for Down syndrome patients compared to controls (p <= 0.008). CONCLUSIONS:
Surgical placement of pressure equalizing tubes results in significant quality of
life improvements in patients with Down syndrome and controls. Problems related
to speech and balance are reported at a higher rate and persist despite
intervention in the Down syndrome population. It is possible that longer follow
up periods and/or more sensitive tools are required to measure speech
improvements in the Down syndrome population after pressure equalizing tube
placement +/- adenoidectomy.
PMID- 27497408
TI - The impact of submandibular duct relocation on drooling and the well-being of
children with neurodevelopmental disabilities.
AB - OBJECTIVE: The aim of this study was to evaluate the impact of a reduction in
drooling after bilateral submandibular duct relocation (SMDR) with sublingual
gland excision on daily life and care, as well as social and emotional
consequences in children and adolescents with neurodevelopmental disabilities.
METHODS: This prospective cohort study included 72 children and adolescents (46
males, 26 females) with moderate to severe drooling, and their caregivers. Mean
age at the time of surgery was 15 years 2 months (SD 4y 3mo). Fifty-two children
were diagnosed with cerebral palsy and 20 had other non-progressive developmental
disabilities. A caregiver questionnaire to document the impact of drooling on
daily care and economic consequences, social interaction and emotional
development and self-esteem was administered before, and 8 and 32 weeks after
surgery. RESULTS: Following bilateral SMDR the mean Visual Analogue Scale (VAS, 0
100) scores demonstrated a significant (p < 0.001) reduction in the severity of
drooling from 81 at baseline to 28 and 36 after 8 and 32 weeks, respectively.
This was accompanied by a decrease in the amount of daily care required and
reduced economic consequences. In addition, an increase in social contact with
other children and adults was reported by caregivers after surgery. CONCLUSION:
Bilateral SMDR with sublingual gland excision provides a significant positive
reduction in daily care of children suffering from drooling. Caregivers also
report positive changes in their child's social interaction and sense of self
esteem.
PMID- 27497409
TI - Etiology and long-term functional swallow outcomes in pediatric unilateral vocal
fold immobility.
AB - OBJECTIVE: Unilateral vocal fold immobility (UVFI) results in deficits in
phonatory, respiratory, and swallow function of the pediatric patient. Little is
known about long-term functional swallow outcomes. METHODS: Medical records of
children diagnosed with UVFI between 2005 and 2014 at a tertiary children's
hospital were retrospectively reviewed. Etiology, laryngoscopy findings, and
swallow status at diagnosis and follow-up were recorded. Swallow outcomes were
compared by etiology using Fisher's exact test. McNemar's test was used to
identify correlations between return of mobility and swallow recovery. Rates of
pneumonia were compared with initial swallow evaluation results using a two
tailed t-test. RESULTS: Eighty-eight patients with UVFI were identified and 73
patients (47% female, mean age 14.4 months, standard deviation (SD) 26.7 months)
had complete medical records. Mean follow up time was 52.7 months (SD 36.8
months). Etiologies included cardiothoracic surgery (68.5%), idiopathic (12.3%),
prolonged intubation (11.0%), central nervous system (CNS) abnormality (5.5%),
and non-cardiac iatrogenic injury to the recurrent laryngeal nerve (2.7%). Forty
seven patients underwent a follow up laryngoscopy, and recovery of vocal fold
(VF) mobility was documented in 42.6% (20/47). At diagnosis, 31.5% fed orally,
compared with 79.5% at follow-up. Direct correlation between recovery of VF
mobility and swallow recovery was not demonstrated. Cardiac etiologies
demonstrated higher rates of swallow recovery than CNS abnormalities (p =
0.0393). Twenty-five children aspirated on initial modified barium swallow (MBS)
and 10 children developed pneumonias at some point during the follow up period.
There was no significant difference in rates of pneumonia in patients with and
without aspiration on MBS. CONCLUSION: Recovery of swallow in children with UVFI
does not directly parallel return of VF mobility. Long-term swallow outcome is
favorable in this population. Initial MBS does not indicate ultimate swallow
outcome.
PMID- 27497410
TI - Postoperative tonsillectomy bleeding complications in children: A comparison of
three surgical techniques.
AB - OBJECTIVE & HYPOTHESIS: Stated in the Null form: There will be no difference in
primary or secondary hemorrhage rate in children undergoing tonsillectomy or
adenotonsillectomy across three surgical techniques: PEAK Plasmablade, electric
monopolar cautery, coblation. STUDY DESIGN: Retrospective chart analysis.
SETTING: Academic Medical Center: Children's Hospital. SUBJECTS & METHODS:
Electronic chart data were collected from patient's age 2-18 years who underwent
tonsillectomy, with or without adenoidectomy, at a tertiary pediatric hospital
between June 2011 to May 2013 by electric monopolar cautery, coblation, or PEAK
PlasmaBlade. Treatment outcomes following each of these surgical approaches,
relative to rate of post-operative primary and secondary bleeding, hospital
admission, and emergency department visits were compared. RESULTS: A total of
1780 patients that had tonsillectomy or adenotonsillectomy were evaluated. There
was a significant difference in bleed rate by age with older patients having more
bleeding post-procedure than their younger counterparts. There was also a
difference in bleeding frequency by diagnosis. Patients with a diagnosis of OSA
were less likely to experience a postoperative bleed than children with either
recurrent tonsillitis or both. Significance was evident between post-op
hemorrhage rate and instrumentation (chi(2) = 11.17, df = 2, p = 0.004). The
majority of bleeds occurred with coblation (58.9%), while PEAK had only 17.8% and
cautery 23%. CONCLUSION: The null hypothesis was rejected. That is, PEAK
PlasmaBlade was safe and effective, with statistically less postoperative
bleeding and ED visits, especially when compared to coblation techniques.
Coblation patients had the highest rates of postoperative bleeding.
PMID- 27497411
TI - Corrigendum to "Identifying predictive factors for long-term complications
following button battery impactions: A case series and literature review" [Int.
J. Pediatr. Otorhinolaryngol. (2016) 198-202].
PMID- 27497412
TI - Presentation and management of nasal foreign bodies at a tertiary children's
hospital in an American metro area.
AB - OBJECTIVES: To examine rates of otolaryngology intervention in children
presenting to our emergency department with nasal foreign bodies, factors
associated with otolaryngology involvement, rates of complications, and details
on nasal button battery exposure. METHODS: All patients presenting with a nasal
foreign body to Children's Hospital Colorado from 2007 to 2012 were identified.
Factors leading to referral to otolaryngology and operative intervention were
examined, as well as complications. RESULTS: 102 patients were included. 36 (35%)
patients were referred to the otolaryngology clinic, of which 58.9% required
operating room intervention. 66 (64.7%) children had their nasal foreign bodies
removed in the emergency room, however 30 (45%) of these were removed by an
otolaryngology resident or attending physician. Overall, 64.7% of nasal foreign
bodies required removal by otolaryngology. Of the 15 objects removed in the
operating room, six were button batteries. No septal perforations occurred as a
result of nasal button battery exposure. Multivariable logistic regression showed
two significant predictors of OR removal: age and disc shaped objects.
CONCLUSION: While emergency department providers are comfortable attempting
removal of nasal foreign bodies, there was a high rate of otolaryngology
intervention. Based on this data, there is a need to educate emergency room
providers on nasal anatomy and techniques for nasal foreign body removal.
PMID- 27497413
TI - Profile of pediatric traditional uvulectomy in North-West Nigeria: The need for
caution and education.
AB - OBJECTIVES: The study assessed the prevalence of complications associated with
traditional uvulectomy and identified factors associated with favorable outcome
after management in a pediatric population in North-Western Nigeria. STUDY DESIGN
AND SETTING: This cross-sectional descriptive study was carried out at the
accident and emergency section as well as at the otolaryngology out-patient
clinic of the Federal Medical Centre, Birnin-Kebbi, Nigeria. METHODS: Patients
with traditional uvulectomy complications were recruited on consecutive basis and
sample size was dependent on the patients seen over the study period. This was
done over a 6 month study period (January 2014-June 2014). RESULTS: A total of
forty one participants, all within the paediatric age group (<15 years)
participated in this study. The age of the participants ranged from 2 to 13 years
while the mean age was 6.17 years +/- 2.47. The <=5 year age group constituted
about 44% of the children studied. Gender distribution noted a slight male
preponderance (Male: Female ratio = 1.05: 1). A total of 58.8% of the
participants were fully immunized, while the Haemoglobin concentration status
(packed cell volume) at hospital presentation of <10 g/dl (<30%) occurred in
34.1% of the participants of the study. The duration of hospital stay in
pediatric patients with post-traditional uvulectomy complications was
significantly associated with the maternal immunization status (p = 0.007). Also,
subjects with completed maternal immunization status had about 0.1 times odds (CI
= 0.19-0.64) likelihood to have a prolonged hospital stay when compared with
subjects whose mothers were partially immunized or not immunized at all.
CONCLUSION/SIGNIFICANCE: In conclusion, this study found that favorable outcome
post-traditional uvulectomy is related to early presentation and maternal
immunization status, but adversely affected by anemia. Traditional uvulectomy
remains a cultural practice that should be discouraged using both advocacy and
legislative measures.
PMID- 27497414
TI - The effects of spinal anesthesia on auditory function in pediatric patients.
AB - OBJECTIVES: Persistent or transient hearing loss (HL) is a less-recognized
complication of spinal anesthesia (SA) in the pediatric population, although it
has been previously reported in adults. The primary aim of this study was to
investigate the effects of SA on auditory function in the pediatric population.
METHODS: After gaining institutional approval and parental consent, 30 American
Society of Anesthesiologists physical status I-II children between 4 and 15 years
undergoing lower extremity orthopedic surgery were enrolled in this prospective
study. Spinal blocks were performed in the midline with a 25G Quincke needle
using 0.5% hyperbaric bupivacaine. Transient evoked otoacoustic emission (TEOAE)
and distortion product otoacoustic emission (DPOAE) tests were administered
before surgery and one-day postoperative. Children with detected HL were retested
on postoperative day seven. Preoperative and postoperative results were compared.
A Wilcoxin Signed-Ranks test (with Bonferroni correction) was used for
statistical analyses. RESULTS: There was no statistically significant HL in the
postoperative period compared to the preoperative period. In 29 of 30 patients,
no difference was detected at any frequency tested. In one patient, TEOAE and
DPOAE tests were found to be decreased on postoperative day one. In this patient,
control tests were found to be improved on postoperative day seven. CONCLUSIONS:
Administration of SA may results in a low probability of transient hearing loss
with no clinical significance in children 4-15 years of age.
PMID- 27497415
TI - Hearing loss in Down Syndrome revisited - 15 years later.
AB - OBJECTIVE: In 2001, the senior authors published a study investigating hearing
loss in young children (ages 11 months to 3.8 years) with Down Syndrome (DS). We
re-visit this same study population to review current audiologic status, the
incidence of pressure equalization tube (PET) placement(s), and rate of tympanic
membrane (TM) perforations. We aim to better understand the natural history of
ear disease and hearing loss in DS and assess potential complications. METHODS:
This retrospective chart review included 57 children with DS who previously
completed in 2006, a 5 year, longitudinal study investigating otolaryngologic
problems in DS. Updated audiologic data was available for 54. Audiograms, age of
ear specific testing, PET placement(s), and tympanic membrane(TM) descriptions
were reviewed. RESULTS: Ages ranged from 14 to 18 years (mean 16.34 years). PET
placement occurred in 88.8%, with mean of 3.5 procedures. 30% of PET's were
placed after age 6. Ear specific testing was obtained in 92.5% (mean age 4.54
years). Normal hearing was present in 44% (right ear) and 38% (left ear).
"Functional" hearing levels, defined as normal or mild hearing loss and speech
reception threshold <= 30 dB, occurred in 83.3%. Sensorineural/mixed hearing loss
was present in 11% (right ear) and 9% (left ear). TM perforations rate was 17%.
No cholesteatomas were found. CONCLUSION: Chronic otitis media and indications
for PET's persist as children with DS age. Although functional hearing occurred
in 83.3%, there was an overall decrease in hearing levels as the children aged.
Tympanic membrane perforations occurred in 17%. Continued surveillance of
otologic and audiologic status in patients with Down syndrome is recommended.
PMID- 27497416
TI - Pediatric sudden sensorineural hearing loss: Etiology, diagnosis and treatment in
20 children.
AB - OBJECTIVES: 1. To report our experience in children with sudden-onset
sensorineural hearing loss (SSNHL). 2. To describe the etiology and management of
children with SSNHL. METHODS: Retrospective review of 20 children with SSNHL,
from 2000 to 2013 at a tertiary pediatric facility. Patients had the following
inclusion criteria: history of normal hearing, hearing loss occurring in less
than 3 days, and audiogram documentation. RESULTS: The average age of patients
presenting with SSNHL is 11 years 3 months (22months-18years). Only 6 (30%)
children presented prior to 2 weeks. Tinnitus (55%) was the most common
associated symptoms followed by otalgia (25%), and vertigo (20%). Eight patients
had bilateral hearing loss, 6 only right and 6 only left. Hearing loss severity
ranged from profound (45%) being most common to mild. Etiology was unknown (30%),
viral (25%), anatomic abnormality (25%), Meniere's disease (5%), autoimmune (5%),
perilymphatic fistula (5%), and suppurative labyrinthitis (5%). Eight patients
had initial treatment with oral steroids of which 50% had improvement on
audiograms. Two patients underwent intratympanic injections, both showed
improvement. Of the 12 patients with no treatment, only 1 had improved hearing.
CONCLUSIONS: The true incidence of pediatric SSNHL is not well established in our
literature. Unique aspects of pediatric SSNHL are delayed presentation and higher
percent of anatomic findings. In our study 70% presented more than 2 weeks after
experiencing symptoms. Anatomic abnormalities are in 40% of patients. Hearing
improvement occurred in 50% of children treated with oral steroids. Intratympanic
steroid treatment is another option but may have practical limitation in the
pediatric population.
PMID- 27497417
TI - Extended cricotracheal resection with posterior costochondral grafting for
complex pediatric subglottic stenosis.
AB - BACKGROUND AND OBJECTIVE: Severe laryngotracheal stenosis in childhood poses a
complex surgical challenge for specialists in airway surgery. Patients with
severe subglottic stenosis with vocal cord involvement are particularly difficult
to manage successfully. The goal of this work was to review our experience with
extended CTR in a cohort of young children with severe SGS and determine which
clinical parameters would be associated with surgical success. METHODS:
Retrospective analysis of the outcome of consecutive patients with severe glottic
subglottic stenosis submitted to an extended double-stage CTR between 2004 and
2014 at a large tertiary referral center. RESULTS: Twenty-five patients met
inclusion criteria, with a mean age of 58.7 months at the time of repair. Overall
decannulation rate was 80% (20/25), with a median time to deannulation of 120
days. Seven patients developed post-operative sequelae (4 arytenoid dislocations,
2 re-stenosis, and 1 anterior commissure adhesion). Patients with these sequelae
had lower overall specific decannulation (42.8%) compared to those without any
sequelae (94.4%) (Chi-square, p = 0.0123) with a longer time to decannulate
(logrank, p = 0.0004). Notably, patients presenting with these sequelae on
average had undergone a longer duration of post-operative stenting (27.14 days)
compared to those presenting without any sequelae (14.8 days) (p = 0.0282).
CONCLUSIONS: Extended CTR is an effective method for resolving a majority of
severe glottic-subglottic stenosis cases in children. Duration of post-operative
stenting may adversely impact overall outcome in these patients.
PMID- 27497418
TI - Hospital clinical trial: Homeopathy (Agraphis nutans 5CH, Thuya occidentalis 5CH,
Kalium muriaticum 9CH and Arsenicum iodatum 9CH) as adjuvant, in children with
otitis media with effusion.
AB - BACKGROUND: Otitis media with effusion (OME) is the most common cause of
paediatric hearing loss. No single treatment has proved its effectiveness. There
is a lack of evidence-based medicine studies in the area of homeopathy. METHOD: A
prospective randomized, double blinded interventional placebo control study was
conducted. Patients, from 2 months to 12 years, with OME diagnosed by pneumatic
otoscopy (PNO) and tympanometry, were randomized into two groups. Both groups
received aerosol therapy (mucolytics and corticosteroids). In addition, the
experimental group (EG) received homeopathy (Agraphis nutans 5CH, Thuya
Occidentalis 5CH, Kalium muriaticum 9CH and Arsenicum iodatum), and the placebo
group (PG) placebo, both of them for 3 months. Patients were evaluated by PNO
examination and tympanometry at baseline, at 45 and 90 days. RESULTS: 97 patients
were enrolled. In the EG, 61.9% of individuals were cured (PNO went from negative
in the 1st visit to positive in the 3rd visit) compared with 56.8% of patients
treated with placebo. 4.8% of patients in the EG suffered a recurrence (positive
PNO in the 2nd visit changed to negative in the 3rd visit) while 11.4% did in the
PG. No significant difference was found. Adverse events were distributed
similarly, except in the case of upper respiratory tract infections, which were
less frequent in EG (3 vs. 13, p: 0.009). CONCLUSION: The homeopathic scheme used
as adjuvant treatment cannot be claimed to be an effective treatment in children
with OME. TRIAL REGISTRATION: EUDRACT number: 2011-006086-17, PROTOCOL code:
55005646.
PMID- 27497419
TI - Tonsillectomies and respiratory complications in children: A look at pre-op
polysomnography risk factors and post-op admissions.
AB - OBJECTIVE: To identify predictors of post-operative respiratory complications in
children undergoing tonsillectomy. METHODS: Consecutive case series with chart
review of children who underwent polysomnography (PSG) and subsequent
tonsillectomy with or without adenoidectomy for obstructive sleep apnea (OSA).
Patients with craniofacial anomalies or significant cardiopulmonary comorbidities
were excluded. Rates of post-surgical respiratory complication were reviewed and
compared to patient specific factors and PSG findings to identify possible risk
factors. RESULTS: Eighty-six patients (mean age 5.3 +/- 2.2 years) were included.
There was a statistically significant (p = 0.03) relationship between an AHI >=40
(AHI40) and post-operative respiratory complications. AHI40 also had the greatest
magnitude of association with postoperative respiratory complications (OR =
5.313). An AHI >=25 (AHI25) was marginally significant (p = 0.067). No
significant difference in outcome occurrence was found when analyzing rates of
complication in patients with BMI above and below 18 (p = 0.20) or oxygen (O2)
nadir above and below 80% (p = 0.09). The AHI ranged from 0 to 112.2, and no
postoperative respiratory complications were identified in children with an AHI
less than 10. CONCLUSIONS: Our results indicate an association between an AHI
>=40 and respiratory complications following an adenotonsillectomy, but we were
not able to observe any significant difference at a cutoff of 25. An association
between BMI or O2 nadir and postoperative respiratory complication was not able
to be identified. Our results support the importance of AHI as a predictor of
postoperative respiratory complications in children undergoing tonsillectomy for
OSA.
PMID- 27497420
TI - The assessment of the Newborn Hearing Screening Program in the Region of Murcia
from 2004 to 2012.
AB - OBJECTIVES: Newborn (NB) auditory deficit has a prevalence of 1-2% in the world.
Since the 1990s different screening programs have been put into practice. The
Newborn Hearing Screening Program has been in operation since 2002 in our
hospital (HCUVA) in Murcia (Spain) and two years later it was introduced into the
whole of the Autonomous Community of the Region of Murcia as part of universal
healthcare. The objective of this study was to analyze and assess its results.
METHOD: The newborn (NB) population is divided into two groups: not-at-risk NBs
and at-risk NBs. In the first case we carry out acoustic otoemissions (AOEs) 48 h
after birth and depending on the result the child is either discharged or, in
negative cases, the infant undergoes a series of tests in a period of 30-45 days
to confirm or rule out the existence of hearing anomalies. In the at-risk group
we combine AOEs with brain trunk potentials (BERA) following the stages in a
decision tree diagram similar to the ones for not-at-risk children in order to
provide a clinical diagnosis in the first three months of life. RESULTS: The
screening performance was assessed for the 156,122 children studied, of which
151,258 belonged to the group of not-at-risk children; and 4864 to the group at
risk of hypoacusia. As a result of the screening only 410 (0.26%) were sent to
consultation, 213 in the not-at-risk group (0.14%) and 197 (24.7%) in the at-risk
group. A total of 7452 false positives were identified (4.7%), 6951 (4.5%) in the
not-at-risk group; and 501 (10.3%) in the group with risk factors; and there were
53 false negatives (0.03%). Sensitivity in the screening program was 88.5%, with
a specificity of 95%. CONCLUSIONS: The Region of Murcia has a Newborn Hearing
Screening Program with tests that provide a high level of sensitivity and
specificity in accordance with the findings of the literature. Our results
endorse the program and the patients were treated in a way that met the objective
of providing a correct diagnosis and the appropriate therapeutic action.
PMID- 27497421
TI - The association of residential mold exposure and adenotonsillar hypertrophy in
children living in damp environments.
AB - BACKGROUND: There are many consequences of mold exposure related to respiratory
system health of children This retrospective cohort study aims to find the
association between adenoid hypertrophy and mold exposure in children living in
damp environments. METHODS: Children with history of recurrent respiratory tract
infections were enrolled in the study between June 2012 and June 2013 and were
followed up for adenoid hypertrophy from June 2013 to June 2016. One hundred and
forty two children were residents of moldy houses and 242 were living in normal
houses. Skin prick test results for 60 common allergens, vitamin D levels, IgE
levels, age, presence of comorbidities such as urticaria, atopic dermatitis,
allergic conjunctivitis, allergic rhinitis, asthma, frequency of upper
respiratory tract infections and lower respiratory tract infections, were
evaluated in both groups. RESULTS: A total of 384 children (mean age +/- standard
deviation = 53.37 +/- 36 months; 198 males and 186 females) were included. The
children were classified into 2 groups (1)Children living normal houses (n = 242)
(2); Children living in damp houses (n = 142) according to mold exposure.
Children with adenoid hypertrophy (p < 0,001) and higher IgE levels (p < 0,001)
were more common in mold exposed group. Lower respiratory tract infections were
more common in children with mold exposure (p < 0,05). Bivariate correlation
analysis showed no significant association between IgE levels and adenoid
hypertrophy. Multiple linear regression analysis was performed to evaluate IgE
levels, vitamin D levels, and presence of adenoid as independent variables; age
as dependent variable among two groups and was found statistically significant (p
< 0,001). Dermatophagoid sensitive group living in damp houses had a significant
increase in adenoid hypertrophy (p = 0,01). Housedustmite sensitive children with
recurrent lower respiratory tract infection and upper respiratory tract infection
were mainly residents of damp houses (p < 0,001). Allergic comorbidities were
significantly more in damp environment group (p < 0,001), but there was no
significant increase in any of the subgroups. CONCLUSIONS: Children with mold
exposure had significantly increased adenoid hypertrophy regardless of their
atopic nature, however, they may have become more sensitized due to other
environmental triggers and genetic factors. In damp environments, sensitization
to dermatophagoids, was significantly increased in children with adenoid
hypertrophy. During the period of infancy, when children were mostly vitamin D
supplemented, they were not sensitized and had normal adenoids. As children with
recurrent respiratory tract infections grow, they tend to have lower vitamin D
levels, become more atopic and tend to have adenoid hypertrophy.
PMID- 27497422
TI - Contrasting patterns of genetic variation in core and peripheral populations of
highly outcrossing and wind pollinated forest tree species.
AB - Gene flow tends to have a homogenising effect on a species' background genetic
variation over large geographical areas. However, it is usually unknown to what
extent the genetic structure of populations is influenced by gene exchange
between core and peripheral populations that may represent stands of different
evolutionary and demographic history. In this study, we looked at the patterns of
population differentiation in Scots pine-a highly outcrossing and wind pollinated
conifer species that forms large ecosystems of great ecological and economic
importance in Europe and Asia. A set of 13 polymorphic nuclear microsatellite
loci was analysed to infer the genetic relationships among 24 populations (676
individuals) from Europe and Asia Minor. The study included specimens from the
primary continuous range and from isolated, marginal stands that are considered
to be autochthonous populations representative of the species' putative refugial
areas. Despite their presumably different histories, a similar level of genetic
variation and no evidence of a population bottleneck was found across the
populations. Differentiation among populations was relatively low (average FST =
0.035); however, the population structure was not homogenous, which was clearly
evident from the allelic frequency spectra and Bayesian assignment analysis.
Significant differentiation over short geographical distances was observed
between isolated populations within the Iberian and Anatolian Peninsulas (Asia
Minor), which contrasted with the absence of genetic differentiation observed
between distant populations e.g., between central and northern Europe. The
analysed populations were assigned to several groups that corresponded to the
geographical regions of their occurrence. These results will be useful in
genetics studies in Scots pine that aim to link nucleotide and phenotypic
variation across the species distribution range and for development of
sustainable breeding and management programs.
PMID- 27497423
TI - Adjuvant endocrine therapy in women with oestrogen-receptor-positive breast
cancer: how should the skeletal and vascular side effects be assessed and
managed?
AB - Adjuvant endocrine therapy provides oncological benefits in women with early
oestrogen-receptor-positive breast cancer, but has adverse effects consequent to
induced oestradiol deficiency. Bone loss is accelerated, predisposing to
increased fracture risk. Metabolic effects include changes in lipid metabolism
and body composition although effects on cardiovascular risk are still unclear.
Women commencing endocrine therapy should be proactively counselled about and
monitored for these and other therapy-related complications including arthralgia
and vasomotor symptoms. We provide strategies for prevention and management of
these adverse effects, based, where available, on randomized controlled trial
evidence specific to breast cancer survivors receiving endocrine treatment.
PMID- 27497424
TI - SIRT1 as a therapeutic target for Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most prevalent cause of dementia in the aging
population worldwide. SIRT1 deacetylation of histones and transcription factors
impinge on multiple neuronal and non-neuronal targets, and modulates stress
response, energy metabolism and cellular senescence/death pathways. Collectively,
SIRT1 activity could potentially affect multiple aspects of hippocampal and
cortical neuron function and survival, thus modifying disease onset and
progression. In this review, the known and potential mechanisms of action of
SIRT1 with regard to AD, and its potential as a therapeutic target, are
discussed.
PMID- 27497425
TI - Pharmacokinetics of ceftriaxone in patients undergoing continuous renal
replacement therapy.
AB - BACKGROUND: The duration of time for which the serum levels exceed the minimum
inhibitory concentration (MIC) is an important pharmacokinetics
(PK)/pharmacodynamics (PD) parameter correlating with efficacy for the
antibiotic, ceftriaxone (CTRX). However, no reports exist regarding the PK or PD
in patients undergoing continuous renal replacement therapy (CRRT). The purpose
of this study was to examine the PK and safety of CTRX in patients undergoing
CRRT in order to establish safer and more effective regimens. METHODS: CTRX (1 g
once a day) was intravenously administered four or more times to nine patients
undergoing CRRT. Blood was collected after administration to measure CTRX
concentrations in serum and the filtration fraction of CRRT by high-performance
liquid chromatography. In addition to calculating PK parameters from serum CTRX,
we (a) estimated by simulation CTRX concentrations when the dose interval was
extended to once every 2 or 3 days, (b) calculated CTRX clearance via CRRT from
CTRX concentrations in the filtration fraction, and (c) assessed the safety of
CTRX use. RESULTS: Total body clearance and the half-life of CTRX were 7.46
mL/min (mean) and 26.5 h, respectively, in patients undergoing CRRT. CTRX was
found in the filtration fraction, and the estimated clearance by CRRT was about
70% of total body clearance. Simulations revealed that even when the dose
interval is increased to 2 or 3 days, CTRX would retain its efficacy.
CONCLUSIONS: Our findings suggest that, depending on the condition of patients
undergoing CRRT, CTRX could be used safely against pathogens with a CTRX MIC <=2
ug/mL, even when extending the dose interval.
PMID- 27497426
TI - Emerging technologies for protease engineering: New tools to clear out disease.
AB - Proteases regulate many biological processes through their ability to activate or
inactive their target substrates. Because proteases catalytically turnover
proteins and peptides, they present unique opportunities for use in
biotechnological and therapeutic applications. However, many proteases are
capable of cleaving multiple physiological substrates. Therefore their activity,
expression, and localization are tightly controlled to prevent unwanted
proteolysis. Currently, the use of protease therapeutics has been limited to a
handful of proteases with narrow substrate specificities, which naturally limits
their toxicity. Wider application of proteases is contingent upon the development
of methods for engineering protease selectivity, activity, and stability. Recent
advances in the development of high-throughput, bacterial and yeast-based methods
for protease redesign have yielded protease variants with novel specificities,
reduced toxicity, and increased resistance to inhibitors. Here, we highlight new
tools for protease engineering, including methods suitable for the redesign of
human secreted proteases, and future opportunities to exploit the catalytic
activity of proteases for therapeutic benefit. Biotechnol. Bioeng. 2017;114: 33
38. (c) 2016 Wiley Periodicals, Inc.
PMID- 27497427
TI - Chromatin programming by developmentally regulated transcription factors: lessons
from the study of haematopoietic stem cell specification and differentiation.
AB - Although the body plan of individuals is encoded in their genomes, each cell type
expresses a different gene expression programme and therefore has access to only
a subset of this information. Alterations to gene expression programmes are the
underlying basis for the differentiation of multiple cell types and are driven by
tissue-specific transcription factors (TFs) that interact with the epigenetic
regulatory machinery to programme the chromatin landscape into transcriptionally
active and inactive states. The haematopoietic system has long served as a
paradigm for studying the molecular principles that regulate gene expression in
development. In this review article, we summarize the current knowledge on the
mechanism of action of TFs regulating haematopoietic stem cell specification and
differentiation, and place this information into the context of general
principles governing development.
PMID- 27497428
TI - Efficacy of antibiotic prophylaxis prior to tympanoplasty for contaminated
cholesteatoma.
AB - OBJECTIVES: To evaluate the efficacy of combined antistaphylococcal and
antipseudomonal preoperative antibiotics for preventing surgical site infections
following tympanoplasty and mastoidectomy with contaminated cholesteatoma. STUDY
DESIGN: Retrospective chart review. METHODS: Medical records of patients who
underwent tympanoplasty +/- mastoidectomy for cholesteatoma were reviewed. Only
cases considered to have contaminated or dirty surgical fields were included. The
primary outcome measure was occurrence of postoperative surgical site infections,
perichondritis, pinna abscess, periotic cellulitis, or periotic abscess requiring
systemic antibiotic therapy or surgical intervention. RESULTS: The charts of 326
patients who underwent tympanoplasty +/- mastoidectomy were reviewed. Of those,
195 met inclusion criteria. Preoperative antibiotics included clindamycin and
ceftazidime or gentamicin. Patients treated with no perioperative antibiotics had
a surgical site infection rate of 11%, and those treated with perioperative
antibiotics had a rate of 1% (P = 0.02). CONCLUSION: Administration of
preoperative antibiotics to cover staphylococcal and pseudomonal species may
prevent surgical site infections with tympanoplasty +/- mastoidectomy for
contaminated cholesteatoma. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2363-2366,
2016.
PMID- 27497429
TI - Freezing behaviours in wintering Cornus florida flower bud tissues revisited
using MRI.
AB - How plant tissues control their water behaviours (phase and movement) under
subfreezing temperatures through adaptative strategies (freezing behaviours) is
important for their survival. However, the fine details of freezing behaviours in
complex organs and their regulation mechanisms are poorly understood, and non
invasive visualization/analysis is required. The localization/density of unfrozen
water in wintering Cornus florida flower buds at subfreezing temperatures was
visualized with high-resolution magnetic resonance imaging (MRI). This allowed
tissue-specific freezing behaviours to be determined. MRI images revealed that
individual anthers and ovules remained stably supercooled to -14 to -21 degrees
C or lower. The signal from other floral tissues decreased during cooling to -7
degrees C, which likely indicates their extracellular freezing. Microscopic
observation and differential thermal analyses revealed that the abrupt breakdown
of supercooled individual ovules and anthers resulted in their all-or-nothing
type of injuries. The distribution of ice nucleation activity in flower buds
determined using a test tube-based assay corroborated which tissues primarily
froze. MRI is a powerful tool for non-invasively visualizing unfrozen tissues.
Freezing events and/or dehydration events can be located by digital comparison of
MRI images acquired at different temperatures. Only anthers and ovules
preferentially remaining unfrozen are a novel freezing behaviour in flower buds.
Physicochemical and biological mechanisms/implications are discussed.
PMID- 27497430
TI - Process performance and product quality in an integrated continuous antibody
production process.
AB - Continuous manufacturing is currently being seriously considered in the
biopharmaceutical industry as the possible new paradigm for producing therapeutic
proteins, due to production cost and product quality related benefits. In this
study, a monoclonal antibody producing CHO cell line was cultured in perfusion
mode and connected to a continuous affinity capture step. The reliable and stable
integration of the two systems was enabled by suitable control loops, regulating
the continuous volumetric flow and adapting the operating conditions of the
capture process. For the latter, an at-line HPLC measurement of the harvest
concentration subsequent to the bioreactor was combined with a mechanistic model
of the capture chromatographic unit. Thereby, optimal buffer consumption and
productivity throughout the process was realized while always maintaining a yield
above the target value of 99%. Stable operation was achieved at three consecutive
viable cell density set points (20, 60, and 40 * 106 cells/mL), together with
consistent product quality in terms of aggregates, fragments, charge isoforms,
and N-linked glycosylation. In addition, different values for these product
quality attributes such as N-linked glycosylation, charge variants, and aggregate
content were measured at the different steady states. As expected, the amount of
released DNA and HCP was significantly reduced by the capture step for all
considered upstream operating conditions. This study is exemplary for the
potential of enhancing product quality control and modulation by integrated
continuous manufacturing. Biotechnol. Bioeng. 2017;114: 298-307. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27497432
TI - Tumour muscle crosstalk more as regulation of muscle wasting - role of exercise.
PMID- 27497431
TI - Genetic rescue in a severely inbred wolf population.
AB - Natural populations are becoming increasingly fragmented which is expected to
affect their viability due to inbreeding depression, reduced genetic diversity
and increased sensitivity to demographic and environmental stochasticity. In
small and highly inbred populations, the introduction of only a few immigrants
may increase vital rates significantly. However, very few studies have quantified
the long-term success of immigrants and inbred individuals in natural
populations. Following an episode of natural immigration to the isolated,
severely inbred Scandinavian wolf (Canis lupus) population, we demonstrate
significantly higher pairing and breeding success for offspring to immigrants
compared to offspring from native, inbred pairs. We argue that inbreeding
depression is the underlying mechanism for the profound difference in breeding
success. Highly inbred wolves may have lower survival during natal dispersal as
well as competitive disadvantage to find a partner. Our study is one of the first
to quantify and compare the reproductive success of first-generation offspring
from migrants vs. native, inbred individuals in a natural population. Indeed, our
data demonstrate the profound impact single immigrants can have in small, inbred
populations, and represent one of very few documented cases of genetic rescue in
a population of large carnivores.
PMID- 27497433
TI - Temperature Influences Chorda Tympani Nerve Responses to Sweet, Salty, Sour,
Umami, and Bitter Stimuli in Mice.
AB - Temperature profoundly affects the perceived intensity of taste, yet we know
little of the extent of temperature's effect on taste in the peripheral nervous
system. Accordingly, we investigated the influence of temperature from 23
degrees C to 43 degrees C in 4 degrees C intervals on the integrated responses
of the chorda tympani (CT) nerve to a large series of chemical stimuli
representing sweet, salty, sour, bitter, and umami tastes in C57BL/J6 mice. We
also measured neural responses to NaCl, Na-gluconate, Na-acetate, Na-sulfate, and
MSG with and without 5 uM benzamil, an epithelial sodium channel (ENaC)
antagonist, to assess the influence of temperature on ENaC-dependent and ENaC
independent response components. Our results showed that for most stimuli (0.5M
sucrose, glucose, fructose, and maltose; 0.02M saccharin and sucralose; 0.5M
NaCl, Na-gluconate, Na-acetate, Na-sulfate, KCl, K-gluconate, K-acetate, and K
sulfate; 0.05M citric acid, acetic acid, and HCl; 0.1M MSG and 0.05M quinine
hydrochloride: QHCl), CT response magnitudes were maximal between 35 degrees C
and 39 degrees C and progressively smaller at cooler or warmer temperatures. In
contrast, the weakest responses to NH4Cl, (NH4)2SO4, and K-sulfate were at the
lowest temperature, with response magnitude increasing monotonically with
increasing temperature, while the largest responses to acetic acid were at the
lowest temperature, with response magnitude decreasing with increasing
temperature. The response to sweet and umami stimuli across temperatures were
similar reflecting the involvement of TRPM5 activity, in contrast to bitter
stimuli, which were weakly affected by temperature. Temperature-modulated
responses to salts and acids most likely operate through mechanisms independent
of ENaC and TRPM5.
PMID- 27497434
TI - beta-Endorphin enhances the phospholipase activity of the dandruff causing fungi
Malassezia globosa and Malassezia restricta.
AB - beta-Endorphin is known to stimulate phospholipase production by Malassezia
pachydermatis during canine dermatoses. The role of beta-endorphin in Malassezia
infection in humans is not well studied. The present study compares the influence
of beta-endorphin on Malassezia globosa and Malassezia restricta isolated from
patients with seborrhoeic dermatitis/dandruff (SD/D) and healthy controls.
Malassezia isolates (five each of the two species from patients and healthy
controls) were grown on modified Dixon's agar with or without 100 nmol/L beta
endorphin. Phospholipase activity was quantified based on its ability to
hydrolyze L-alpha-phosphatidylcholine dimyristoyl (phospholipid substrate). Free
fatty acid was measured by a colorimetry method. In isolates from patients, the
phospholipase activity significantly increased after exposure to beta-endorphin
(M. globosa, P = .04; M. restricta, P = .001), which did not occur in isolates
from healthy controls. Moreover, after beta-endorphin exposure the patient
isolates had significantly higher (P = .0004) phospholipase activity compared to
the healthy control isolates. The results suggest that isolates of M. globosa and
M. restricta from patients may differ from those of healthy humans.
PMID- 27497436
TI - Effects of time and temperature on 48 routine chemistry, haematology and
coagulation analytes in whole blood samples.
AB - Background Phlebotomy for the purpose of blood analysis is often performed at
remote locations, and samples are usually temporarily stored before transport to
a central laboratory for analysis. The circumstances during storage and shipment
may not meet the necessary requirements. If analysed anyway, false results may be
generated. We therefore examined the influence of precentrifugation time and
temperature of the most frequently requested tests in whole blood. Methods
Healthy volunteers donated blood in which 48 analytes were tested. Routine
chemistry was performed in lithium heparin tubes, haematology in
ethylenediaminetetraacetic acid tubes, coagulation in citrate tubes and glucose
in sodium fluoride tubes. One tube was measured directly. The others were kept at
different temperatures (4, 8, 20 or 30C) and stored for 4, 6, 8 or 24 h before
analysis. Additionally, some analytes were examined at 12, 16, 24 and 28C. The
mean percentage deviation was compared with different decision levels, including
the total allowable error. Results When using the total allowable error as an
acceptable limit, most of the investigated analytes remained stable. However,
bicarbonate is unstable at almost all tested time-points and temperatures.
Calcium, lactate dehydrogenase, potassium and sodium are particularly affected at
low temperatures, while phosphate is mainly affected at and above room
temperature after 8 h. Conclusion We established the influence of time and
temperature on a broad range of analytes, which may be applied to set the limits
in transportation and storage of whole blood samples.
PMID- 27497435
TI - Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis.
AB - Mitochondria are essential organelles that adapt to stress and environmental
changes. Among the nutrient signals that affect mitochondrial form and function
is iron, whose depletion initiates a rapid and reversible decrease in
mitochondrial biogenesis through unclear means. Here we demonstrate that, unlike
the canonical iron-induced alterations to transcript stability, loss of iron
dampens the transcription of genes encoding mitochondrial proteins with no change
to transcript half-life. Using mass spectrometry, we demonstrate that these
transcriptional changes are accompanied by dynamic alterations to histone
acetylation and methylation levels that are largely reversible upon
readministration of iron. Moreover, histone deacetylase inhibition abrogates the
decreased histone acetylation observed upon iron deprivation and restores normal
transcript levels at genes encoding mitochondrial proteins. Collectively, we
demonstrate that deprivation of an essential nutrient induces transcriptional
repression of organellar biogenesis involving epigenetic alterations.
PMID- 27497437
TI - Non-fatal injuries treated outside a hospital in Hunan, China: results from a
household interview survey.
AB - Background: Injury morbidity data are collected through hospital-based
surveillance in many countries. We assessed the extent of non-fatal injures
treated outside a hospital. Methods: Data from the first provincial health
household interview survey of Hunan, China, conducted in 2013, were used. Injury
events were identified and included as medically significant when any of the
following circumstances occurred in the prior 14 days: (i) receiving medical
treatment from a doctor at a hospital following an injury; (ii) receiving medical
treatment by self or others outside a hospital following an injury (e.g. taking
medications, or receiving massage or hot compress); and/or (iii) being off work
or school, or in bed for more than 1 day, following an injury. The 2-week
prevalence of non-fatal injuries and 95% confidence intervals were calculated. We
calculated the proportion of injury events treated outside a hospital and the
reasons for not visiting a hospital for injury events occurring during the
previous 2 weeks. Results: We captured 56 injury events during the previous 2
weeks. The weighted injury prevalence was 4.9 per 1000 persons during the last 2
weeks (95% confidence interval: 2.9-6.9 per 1000 persons). Of the 56 events, 14
(weighted proportion 41.2%) were treated outside a hospital. Primary explanations
for skipping hospital visits included perceiving injuries were too minor and
economic limitations to travel to hospitals or seek treatment. Conclusion:
Results imply the burden of non-fatal injury may be underestimated by hospital
based surveillance systems such as that used in China.
PMID- 27497438
TI - The prevalence and impact of risk factors for ethnic differences in loneliness.
AB - BACKGROUND: Previous studies have demonstrated that loneliness is more frequently
present in citizens of ethnic minority groups than in natives. The current study
investigates whether ethnic differences in emotional and social loneliness
between Moroccan, Turkish, Surinamese and Dutch adults living in the Netherlands
are due to ethnic differences in the presence and/or impact of an array of
possible risk factors, such as partnership, health and socioeconomic status.
METHODS: The data were collected in 2012 as a part of a general health
questionnaire of the Public Health Services in the four major cities of the
Netherlands, containing 20.047 Dutch, 1.043 Moroccan, 1.197 Turkish and 1.900
Surinamese respondents. RESULTS: Structural equation models showed that ethnic
differences in emotional and social loneliness can be ascribed to ethnic
differences in the prevalence and impact of several risk factors. Main findings
were that all three ethnic minority groups reported feeling less healthy and more
discriminated against than the Dutch group, which was related to increased
loneliness. Perceived financial difficulties and people in the neighbourhood not
getting along had more impact on feelings of loneliness for the Turkish group
than loneliness for the other ethnic groups. Furthermore, members of the Turkish
group were found more at risk to feel anxious or depressed, which was in turn
related to increased loneliness. CONCLUSIONS: Policy makers are encouraged to
develop multifaceted prevention strategies concerning those risk factors that are
most changeable, thereby focusing per risk factor on those ethnic groups for
which it is an important contribution to loneliness.
PMID- 27497439
TI - genipe: an automated genome-wide imputation pipeline with automatic reporting and
statistical tools.
AB - : Genotype imputation is now commonly performed following genome-wide genotyping
experiments. Imputation increases the density of analyzed genotypes in the
dataset, enabling fine-mapping across the genome. However, the process of
imputation using the most recent publicly available reference datasets can
require considerable computation power and the management of hundreds of large
intermediate files. We have developed genipe, a complete genome-wide imputation
pipeline which includes automatic reporting, imputed data indexing and
management, and a suite of statistical tests for imputed data commonly used in
genetic epidemiology (Sequence Kernel Association Test, Cox proportional hazards
for survival analysis, and linear mixed models for repeated measurements in
longitudinal studies). AVAILABILITY AND IMPLEMENTATION: The genipe package is an
open source Python software and is freely available for non-commercial use (CC BY
NC 4.0) at https://github.com/pgxcentre/genipe Documentation and tutorials are
available at http://pgxcentre.github.io/genipe CONTACT: louis
philippe.lemieux.perreault@statgen.org or marie
pierre.dube@statgen.orgSupplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 27497440
TI - scphaser: haplotype inference using single-cell RNA-seq data.
AB - Determination of haplotypes is important for modelling the phenotypic
consequences of genetic variation in diploid organisms, including cis-regulatory
control and compound heterozygosity. We realized that single-cell RNA-seq (scRNA
seq) data are well suited for phasing genetic variants, since both
transcriptional bursts and technical bottlenecks cause pronounced allelic
fluctuations in individual single cells. Here we present scphaser, an R package
that phases alleles at heterozygous variants to reconstruct haplotypes within
transcribed regions of the genome using scRNA-seq data. The devised method
efficiently and accurately reconstructed the known haplotype for >=93% of
phasable genes in both human and mouse. It also enables phasing of rare and de
novo variants and variants far apart within genes, which is hard to attain with
population-based computational inference. AVAILABILITY AND IMPLEMENTATION:
scphaser is implemented as an R package. Tutorial and code are available at
https://github.com/edsgard/scphaser CONTACT: rickard.sandberg@ki.se SUPPLEMENTARY
INFORMATION: Supplementary data are available at Bioinformatics online.
PMID- 27497441
TI - Metrics for rapid quality control in RNA structure probing experiments.
AB - MOTIVATION: The diverse functionalities of RNA can be attributed to its capacity
to form complex and varied structures. The recent proliferation of new structure
probing techniques coupled with high-throughput sequencing has helped RNA studies
expand in both scope and depth. Despite differences in techniques, most
experiments face similar challenges in reproducibility due to the stochastic
nature of chemical probing and sequencing. As these protocols expand to
transcriptome-wide studies, quality control becomes a more daunting task. General
and efficient methodologies are needed to quantify variability and quality in the
wide range of current and emerging structure probing experiments. RESULTS: We
develop metrics to rapidly and quantitatively evaluate data quality from
structure probing experiments, demonstrating their efficacy on both small
synthetic libraries and transcriptome-wide datasets. We use a signal-to-noise
ratio concept to evaluate replicate agreement, which has the capacity to identify
high-quality data. We also consider and compare two methods to assess variability
inherent in probing experiments, which we then utilize to evaluate the coverage
adjustments needed to meet desired quality. The developed metrics and tools will
be useful in summarizing large-scale datasets and will help standardize quality
control in the field. AVAILABILITY AND IMPLEMENTATION: The data and methods used
in this article are freely available at:
http://bme.ucdavis.edu/aviranlab/SPEQC_software CONTACT:
saviran@ucdavis.eduSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27497442
TI - A novel copy number variants kernel association test with application to autism
spectrum disorders studies.
AB - MOTIVATION: Copy number variants (CNVs) have been implicated in a variety of
neurodevelopmental disorders, including autism spectrum disorders, intellectual
disability and schizophrenia. Recent advances in high-throughput genomic
technologies have enabled rapid discovery of many genetic variants including
CNVs. As a result, there is increasing interest in studying the role of CNVs in
the etiology of many complex diseases. Despite the availability of an
unprecedented wealth of CNV data, methods for testing association between CNVs
and disease-related traits are still under-developed due to the low prevalence
and complicated multi-scale features of CNVs. RESULTS: We propose a novel CNV
kernel association test (CKAT) in this paper. To address the low prevalence, CNVs
are first grouped into CNV regions (CNVR). Then, taking into account the multi
scale features of CNVs, we first design a single-CNV kernel which summarizes the
similarity between two CNVs, and next aggregate the single-CNV kernel to a CNVR
kernel which summarizes the similarity between two CNVRs. Finally, association
between CNVR and disease-related traits is assessed by comparing the kernel-based
similarity with the similarity in the trait using a score test for variance
components in a random effect model. We illustrate the proposed CKAT using
simulations and show that CKAT is more powerful than existing methods, while
always being able to control the type I error. We also apply CKAT to a real
dataset examining the association between CNV and autism spectrum disorders,
which demonstrates the potential usefulness of the proposed method. AVAILABILITY
AND IMPLEMENTATION: A R package to implement the proposed CKAT method is
available at http://works.bepress.com/debashis_ghosh/ CONTACTS: xzhan@fhcrc.org
or debashis.ghosh@ucdenver.eduSupplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 27497443
TI - WebSTAR3D: a web server for RNA 3D structural alignment.
AB - : The WebSTAR3D web server is a user-friendly online interface for the alignment
of RNA 3D structures. The website takes as input two files, each of which can be
in either PDB or mmCIF format, containing the desired structures to align, via a
PDB code or user upload. In return, the user is presented with a visualization of
the aligned structures in Jmol or JSmol, along with the corresponding sequence
alignment, and the option to download the nucleotide mapping of the structures
and a PDB file containing the aligned, superimposed structures. AVAILABILITY AND
IMPLEMENTATION: The WebSTAR3D is available at http://rna.ucf.edu/WebSTAR3D
CONTACT: shzhang@cs.ucf.edu.
PMID- 27497444
TI - Rule-based modeling with Virtual Cell.
AB - Rule-based modeling is invaluable when the number of possible species and
reactions in a model become too large to allow convenient manual specification.
The popular rule-based software tools BioNetGen and NFSim provide powerful
modeling and simulation capabilities at the cost of learning a complex scripting
language which is used to specify these models. Here, we introduce a modeling
tool that combines new graphical rule-based model specification with existing
simulation engines in a seamless way within the familiar Virtual Cell (VCell)
modeling environment. A mathematical model can be built integrating explicit
reaction networks with reaction rules. In addition to offering a large choice of
ODE and stochastic solvers, a model can be simulated using a network free
approach through the NFSim simulation engine. AVAILABILITY AND IMPLEMENTATION:
Available as VCell (versions 6.0 and later) at the Virtual Cell web site
(http://vcell.org/). The application installs and runs on all major platforms and
does not require registration for use on the user's computer. Tutorials are
available at the Virtual Cell website and Help is provided within the software.
Source code is available at Sourceforge. CONTACT: vcell_support@uchc.edu
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
online.
PMID- 27497445
TI - Synergistic Activation of RD29A Via Integration of Salinity Stress and Abscisic
Acid in Arabidopsis thaliana.
AB - Plants perceive information from the surroundings and elicit appropriate
molecular responses. How plants dynamically respond to combinations of external
inputs is yet to be revealed, despite the detailed current knowledge of
intracellular signaling pathways. We measured dynamics of Response-to-Dehydration
29A (RD29A) expression induced by single or combined NaCl and ABA treatments in
Arabidopsis thaliana. RD29A expression in response to a combination of NaCl and
ABA leads to unique dynamic behavior that cannot be explained by the sum of
responses to individual NaCl and ABA. To explore the potential mechanisms
responsible for the observed synergistic response, we developed a mathematical
model of the DREB2 and AREB pathways based on existing knowledge, where NaCl and
ABA act as the cognate inputs, respectively, and examined various system
structures with cross-input modulation, where non-cognate input affects
expression of the genes involved in adjacent signaling pathways. The results from
the analysis of system structures, combined with the insights from microarray
expression profiles and model-guided experiments, predicted that synergistic
activation of RD29A originates from enhancement of DREB2 activity by ABA. Our
analysis of RD29A expression profiles demonstrates that a simple mathematical
model can be used to extract information from temporal dynamics induced by
combinatorial stimuli and produce experimentally testable hypotheses.
PMID- 27497446
TI - NDH-Mediated Cyclic Electron Flow Around Photosystem I is Crucial for C4
Photosynthesis.
AB - C4 photosynthesis exhibits efficient CO2 assimilation in ambient air by
concentrating CO2 around ribulose 1,5-bisphosphate carboxylase/oxygenase
(Rubisco) through a metabolic pathway called the C4 cycle. It has been suggested
that cyclic electron flow (CEF) around PSI mediated by chloroplast NADH
dehydrogenase-like complex (NDH), an alternative pathway of photosynthetic
electron transport (PET), plays a crucial role in C4 photosynthesis, although the
contribution of NDH-mediated CEF is small in C3 photosynthesis. Here, we
generated NDH-suppressed transformants of a C4 plant, Flaveria bidentis, and
showed that the NDH-suppressed plants grow poorly, especially under low-light
conditions. CO2 assimilation rates were consistently decreased in the NDH
suppressed plants under low and medium light intensities. Measurements of non
photochemical quenching (NPQ) of Chl fluorescence, the oxidation state of the
reaction center of PSI (P700) and the electrochromic shift (ECS) of pigment
absorbance indicated that proton translocation across the thylakoid membrane is
impaired in the NDH-suppressed plants. Since proton translocation across the
thylakoid membrane induces ATP production, these results suggest that NDH
mediated CEF plays a role in the supply of ATP which is required for C4
photosynthesis. Such a role is more crucial when the light that is available for
photosynthesis is limited and the energy production by PET becomes rate
determining for C4 photosynthesis. Our results demonstrate that the physiological
contribution of NDH-mediated CEF is greater in C4 photosynthesis than in C3
photosynthesis, suggesting that the mechanism of PET in C4 photosynthesis has
changed from that in C3 photosynthesis accompanying the changes in the mechanism
of CO2 assimilation.
PMID- 27497447
TI - The Arabidopsis Iron-Sulfur Protein GRXS17 is a Target of the Ubiquitin E3
Ligases RGLG3 and RGLG4.
AB - The stability of signaling proteins in eukaryotes is often controlled by post
translational modifiers. For polyubiquitination, specificity is assured by E3
ubiquitin ligases. Although plant genomes encode hundreds of E3 ligases, only few
targets are known, even in the model Arabidopsis thaliana. Here, we identified
the monothiol glutaredoxin GRXS17 as a substrate of the Arabidopsis E3 ubiquitin
ligases RING DOMAIN LIGASE 3 (RGLG3) and RGLG4 using a substrate trapping
approach involving tandem affinity purification of RING-dead versions.
Simultaneously, we used a ubiquitin-conjugating enzym (UBC) panel screen to
pinpoint UBC30 as a cognate E2 UBC capable of interacting with RGLG3 and RGLG4
and mediating auto-ubiquitination of RGLG3 and ubiquitination of GRXS17 in vitro.
Accordingly, GRXS17 is ubiquitinated and degraded in an RGLG3- and RGLG4
dependent manner in planta. The truncated hemoglobin GLB3 also interacted with
RGLG3 and RGLG4 but appeared to obstruct RGLG3 ubiquitination activity rather
than being its substrate. Our results suggest that the RGLG family is intimately
linked to the essential element iron.
PMID- 27497448
TI - "It Can't Happen Soon Enough." The Role of Readiness in Residential Moves by
Older Parents.
AB - My father moved from his home of 92 years to a care community in a distant
location. This is the story of his move, from the perspective of a gerontologist
and soon-to-be young-old daughter. I describe the events that prompted my
father's decision to make the move, how I chose the care community, the
transition arrangements, and the outcomes. I discuss key factors that contributed
to the successful transition, all with a focus on readiness. Other factors
included drawing on my knowledge as a gerontologist, using informal networks to
identify a care community, visiting the care community repeatedly, and
communicating openly and often with family. I briefly describe my father's
quality of life after the move. I examine my experiences in the context of
relevant research in gerontology, recommend how gerontologists can manage
transitions to care communities for their aging parents, and offer suggestions
for research.
PMID- 27497449
TI - Interconnections Between My Research and Experience as a Caregiver: Impacts on
Empirical and Personal Perspectives.
AB - Shortly after I received my first R01 grant to study the health effects of
caregiving, my sister and I became caregivers to our father. For the next 13
years, we helped him with activities of daily living (ADLs), accompanied him to
doctors' appointments, arranged for home health care, and finally for home
hospice. At first, I was able to connect our assistance with ADLs, frustration
with coordinating his care, and our psychological stress with my epidemiologic
studies. My familiarity with the language of caregiving and long-term care helped
us to navigate the medical and home care systems, and to be advocates for my
father. However, as my father's health declined, I felt an increasing disconnect
between my research and my experience: communicating with physicians and other
care providers, responding to crises and conversations with my sister about
placing our father in a nursing home were greater sources of stress than my
father's dementia. These discrepancies made me realize that I could help
caregivers more by helping them to negotiate these challenges than through
performing quantitative research. So I enrolled in a counseling psychology
program. My manuscript will chronicle the ways that caregiving changed me; how my
professional work did and did not help me as a caregiver; how the developmental
and family theories that I am learning in my psychology classes have expanded my
understanding of stressors facing adult child caregivers, and how this entire
experience ties into generativity and Third Chapter careers that build on midlife
experiences.
PMID- 27497450
TI - The Insiders as Outsiders: Professionals Caring for an Aging Parent.
AB - As professionals in geriatric medicine and social work, we are caregivers for our
widowed mother of 90 years, a woman with neurocognitive disorder and multiple
medical conditions. She has had repeated, problematic encounters with the health
care system over the past 4 years. Caring successfully for an aging parent
requires a comprehensive understanding of her unique medical, psychological, and
functional status; need for social support; and overall goals of care. Poor
communication between and among clinical teams-and with patients and families-is
ubiquitous. The patient and family are not consistently listened to, or
integrated, into the clinical team. We recount our experiences of one
hospitalization and how we addressed the recurring obstacles we faced. Our
training and experience gave us a firm understanding of the hazards of
hospitalizing an elderly person and the need to be present, engaged, attentive,
active, and vigilant. We caught and corrected major mistakes: failure to follow
up abnormal test results, multiple medication errors, undertreatment of pain,
poor fall prevention, and inappropriate assessment and placement for
rehabilitation. In a dysfunctional health care system, the family is, and must
be, the ultimate fail-safe mechanism. We identify potentially effective solutions
for the problems we encountered: adoption of dementia-sensitive and patient- and
family-centered care, improved communication, better management of information
(including better systems for monitoring lab results and for dispensing and
reconciling medications), expediting care, changing reimbursement and regulation,
and improving discharge planning and placement.
PMID- 27497451
TI - Synchronizing the patient-centered model and health behavior change.
PMID- 27497452
TI - Caring for LGBTQ patients: Methods for improving physician cultural competence.
AB - This article summarizes the components of a curriculum used to teach family
medicine residents and faculty about LGBTQ patients' needs in a family medicine
residency program in the Pacific Northwest region of the United States. This
curriculum was developed to provide primary care physicians and physicians-in
training with skills to provide better health care for LGBTQ-identified patients.
The curriculum covers topics that range from implicit and explicit bias and
appropriate terminology to techniques for crafting patient-centered treatment
plans. Additionally, focus is placed on improving the understanding of specific
and unique barriers to competent health care encountered by LGBTQ patients.
Through facilitated discussion, learners explore the health disparities that
disproportionately affect LGBTQ individuals and develop skills that will improve
their ability to care for LGBTQ patients. The goal of the curriculum is to teach
family medicine faculty and physicians in training how to more effectively
communicate with and treat LGBTQ patients in a safe, non-judgmental, and
welcoming primary care environment.
PMID- 27497453
TI - Patient perceptions of weight loss: Implications for patients, providers, and
trainees.
AB - OBJECTIVES: The prevalence of overweight and obese individuals in the United
States is growing, and primary health care represents a setting in which
providers may address weight with their patients. However, many providers and
medical trainees feel ill-prepared to address the full scope of complexities
associated with weight loss. This study sought to investigate patients'
perceptions of the barriers and facilitators they encountered in their weight
loss journeys. The results of the mixed-methods study will be used to inform a
better understanding among providers and medical students of how to address
weight loss with their patients. This study was approved by the institutional
review board of Medical College of Wisconsin. METHODS: Participants were selected
from patient panels at a Family Medicine Residency Program. Participants who
enrolled in the study completed a survey that collected attitudes and behaviors
about weight loss and demographics. The patients also participated in a 60- to 90
min guided interview. Interviews were transcribed verbatim and analyzed using
open-coding techniques and principles of grounded theory. RESULTS: To date, five
participants completed the study. All were female with a mean age of 52 years.
Two primary themes emerged from a grounded theory model. The first theme centered
on individual's knowledge, attitudes, and behaviors to lost weight. The second
theme emphasized that societal relationships serve as both a barrier and a
facilitator to weight loss. CONCLUSION: The overarching conclusion of this study
is that individuals often have the knowledge to make positive health behaviors
changes, but multiple factors may prohibit this from occurring. When a supportive
environment exists, healthy behavior changes are more attainable. Physicians, mid
level providers, and medical trainees and even medical systems can provide
appropriate support to join the patient on their weight loss journey.
PMID- 27497454
TI - Comprehensive care of pain: Developing systems and tools to improve patient care
and resident education.
AB - Chronic non-cancer pain is a common condition associated with tremendous risk for
morbidity and mortality. In many settings, the management of chronic non-cancer
pain by primary care providers, although customary, can be difficult due to
inadequate training and conflicts between patient expectations and best
practices. Resident physicians, faculty, and staff of this family medicine
residency program developed a comprehensive chronic pain management program to
address these issues while improving patient outcomes. The program was aligned
with evidence-based chronic non-cancer pain management strategies yet tailored to
the needs of the providers and patients and the strengths of the clinic. In the
end, the societal demand for improved chronic non-cancer pain management resulted
in a massive curricular and clinical practice overhaul for this residency
program.
PMID- 27497455
TI - The elephant in the room: Dialogues about race within cross-cultural supervisory
relationships.
AB - OBJECTIVES: For centuries, the concept of race, a uniquely pervasive social
construct, has often complicated dialogue and interactions between groups of
people. This study assessed perceptions and attitudes of faculty and trainees
with varied racial backgrounds within graduate medical and psychology programs.
Self-reported responses addressed potential barriers and facilitating factors
required for meaningful conversations about race. METHODS: A brief 18-question
survey was developed and administered electronically to three professional and
academic Listservs within a large metropolitan city in northeast United States.
Quantitative and qualitative analysis were conducted using SPSS Statistical
Software and Text analyzer. RESULTS: Results revealed that among participants (N
= 57) a majority experienced cross-racial supervision, and more than half
indicated engaging in conversations about race within supervision. Respondents
endorsed lack of comfort and lack of opportunity/time as significant barriers to
discussing race within supervision. When race-related dialogues occurred, a
majority of supervisees and supervisors found it beneficial. Most Supervisors of
Color(a) actively initiated these conversations in supervision, while White
supervisees endorsed the least benefit from these conversations. Contrary to our
expectations, few respondents endorsed limited training as a barrier. DISCUSSION:
The current study revealed cross-racial dialogues about race may be occurring
frequently in supervisory relationships. Supervisees of Color reported benefiting
from these dialogues, in contrast to their White counterparts, who endorsed the
least benefit. Lack of comfort in supervisory relationships appears to be a
significant barrier to having these conversations. Therefore, it is important for
supervisors to create supervisory relationships emphasizing safety and comfort.
Directions for future research are discussed.
PMID- 27497456
TI - Innovative patient-centered skills training addressing challenging issues in
cancer communications: Using patient's stories that teach.
AB - This workshop demonstrated the utility of a patient-centered web-based/digital
Breaking Bad News communication training module designed to educate learners of
various levels and disciplines. This training module is designed for independent,
self-directed learning as well as group instruction. These interactive
educational interventions are based upon video-recorded patient stories.
Curriculum development was the result of an interdisciplinary, collaborative
effort involving faculty from the East Tennessee State University (ETSU) Graduate
Storytelling Program and the departments of Family and Internal Medicine at the
James H. Quillen College of Medicine. The specific goals of the BBN training
module are to assist learners in: (1) understanding a five-step patient-centered
model that is based upon needs, preferences, and expectations of patients with
cancer and (2) individualizing communication that is consistent with patient
preferences in discussing emotions, informational detail, prognosis and timeline,
and whether or not to discuss end-of-life issues. The pedagogical approach to the
training module is to cycle through Emotional Engagement, Data, Modeled
Practices, Adaptation Opportunities, and Feedback. The communication skills
addressed are rooted in concepts found within the Reaching Common Ground
communication training. A randomized control study investigating the
effectiveness of the Breaking Bad News module found that medical students as well
as resident physicians improved their communication skills as measured by an
Objective Structured Clinical Examination. Four other similarly designed modules
were also created: Living Through Treatment, Transitions: From Curable to
Treatable/From Treatable to End-of-Life, Spirituality, and Family.
PMID- 27497457
TI - Integrating motivational interviewing and narrative therapy to teach behavior
change to family medicine resident physicians.
AB - INTRODUCTION: Motivational interviewing is a useful skill to address the common
problem of patient ambivalence regarding behavior change by uncovering and
strengthening a person's own motivation and commitment to change. The Family
Medicine Milestones underline the need for clear teaching and monitoring of
skills in communication and behavior change in Family Medicine postgraduate
training settings. METHODS: This article reports the integration of a
motivational interviewing curriculum into an existing longitudinal narrative
therapy-based curriculum on patient-centered communication. OUTCOMES: Observed
structured clinical examination for six participants indicate that intern
physicians are able to demonstrate moderate motivational interviewing skill after
a brief 2-h workshop. Participant self-evaluations for 16 participants suggest a
brief 2-h curriculum was helpful at increasing importance of learning
motivational interviewing by participants, and that participants desire further
training opportunities. CONCLUSION: A brief motivational interviewing curriculum
can be integrated into existing communication training in a Family Medicine
residency training program.
PMID- 27497458
TI - Improving patient-centered communication while using an electronic health record:
Report from a curriculum evaluation.
AB - INTRODUCTION: Researchers and clinicians are concerned about the impact of
electronic health record use and patient-centered communication. Training about
patient-centered clinical communication skills with the electronic health record
may help clinicians adapt and remain patient-centered. METHODS: We developed an
interactive workshop eliciting challenges and opportunities of working with the
electronic health record in clinical practice, introduction of specific patient
centered behaviors and mindful practice techniques, and video demonstrating
contrasts in common behavior and "better practices." One hundred thirty-nine
resident physicians and faculty supervisors in five residency training programs
at the University of Rochester Medical Center participated in the workshops.
Participants were asked to complete an 11-item survey of behaviors related to
their use of the electronic health record prior to training and after attending
training. We used paired t-tests to assess changes in self-reported behavior from
pre-intervention to post-intervention. RESULTS: We trained 139 clinicians in the
workshops; 110 participants completed the baseline assessment and 39 completed
both the baseline and post-intervention assessment. Data from post-curriculum
respondents found a statistically significant increase in "I told the patient
when turning my attention from the patient to the computer," from 60% of the time
prior to the training to 70% of the time after. DISCUSSION: Data from our program
evaluation demonstrated improvement in one communication behavior. Sample size
limited the detection of other changes; further research should investigate
effective training techniques for patient-centered communication while using the
electronic health record.
PMID- 27497459
TI - Inosine enhances recovery of grasp following cortical injury to the primary motor
cortex of the rhesus monkey.
AB - BACKGROUND: Inosine, a naturally occurring purine nucleoside, has been shown to
stimulate axonal growth in cell culture and promote corticospinal tract axons to
sprout collateral branches after stroke, spinal cord injury and TBI in rodent
models. OBJECTIVE: To explore the effects of inosine on the recovery of motor
function following cortical injury in the rhesus monkey. METHODS: After being
trained on a test of fine motor function of the hand, monkeys received a lesion
limited to the area of the hand representation in primary motor cortex. Beginning
24 hours after this injury and continuing daily thereafter, monkeys received
orally administered inosine (500 mg) or placebo. Retesting of motor function
began on the 14th day after injury and continued for 12 weeks. RESULTS: During
the first 14 days after surgery, there was evidence of significant recovery
within the inosine-treated group on measures of fine motor function of the hand,
measures of hand strength and digit flexion. While there was no effect of
treatment on the time to retrieve a reward, the treated monkeys returned to
asymptotic levels of grasp performance significantly faster than the untreated
monkeys. Additionally, the treated monkeys evidenced a greater degree of recovery
in terms of maturity of grasp pattern. CONCLUSION: These findings demonstrate
that inosine can enhance recovery of function following cortical injury in
monkeys.
PMID- 27497460
TI - Variability of hemodynamic parameters using the common viscosity assumption in a
computational fluid dynamics analysis of intracranial aneurysms.
AB - BACKGROUND: In most simulations of intracranial aneurysm hemodynamics, blood is
assumed to be a Newtonian fluid. However, it is a non-Newtonian fluid, and its
viscosity profile differs among individuals. Therefore, the common viscosity
assumption may not be valid for all patients. OBJECTIVE: This study aims to test
the suitability of the common viscosity assumption. METHODS: Blood viscosity
datasets were obtained from two healthy volunteers. Three simulations were
performed for three different-sized aneurysms, two using measured value-based non
Newtonian models and one using a Newtonian model. The parameters proposed to
predict an aneurysmal rupture obtained using the non-Newtonian models were
compared with those obtained using the Newtonian model. RESULTS: The largest
difference (25%) in the normalized wall shear stress (NWSS) was observed in the
smallest aneurysm. Comparing the difference ratio to the NWSS with the Newtonian
model between the two Non-Newtonian models, the difference of the ratio was
17.3%. CONCLUSIONS: Irrespective of the aneurysmal size, computational fluid
dynamics simulations with either the common Newtonian or non-Newtonian viscosity
assumption could lead to values different from those of the patient-specific
viscosity model for hemodynamic parameters such as NWSS.
PMID- 27497461
TI - A novel classification of screw placement accuracy in the cervical spine.
AB - BACKGROUND: Goal of this study is to present an easily reproducible and reliable
measurement to evaluate accuracy of screw placement in cervical spine. METHODS:
Accuracy of cervical screw position was assessed in 52 patients treated with 163
screws. Each patient receiving pedicle, transarticular C1/2, lateral mass, or
laminar screws and postoperative CT scan was included. Placement position was
categorized in 5 grades: Grade 1 is ideal with pedicle wall perforation < 1 mm,
grade 2 < 2 mm, grade 3 < 3 mm, and grade 4 < 4 mm. Grade 5 > 4 mm and/or
obstruction of transverse foramen by more than half a screw diameter. Intraclass
correlation coefficient (ICC) values were assessed for inter- and intraobserver
reliability. RESULTS: The mode of individual evaluations was calculated to assign
a single value to each screw. This yielded 89 grade 1 (54.6%), 48 grade 2
(29.4%), 14 grade 3 (8.6%), 3 grade 4 (1.8%), and 9 grade 5 (5.5%) screws.
Intraobserver reliability ICC was 0.966 and 0.959 for measurements. Interobserver
reliability ICC was 0.938. CONCLUSION: This study introduces a reliable
classification of cervical spine instrumentation with various screw types. This
should enable the use of a uniform and reproducible, and thus comparable
classification for screw position in cervical spine.
PMID- 27497462
TI - The QuickLine IL-6 lateral flow immunoassay improves the rapid intraoperative
diagnosis of suspected periprosthetic joint infections.
AB - BACKGROUND: When deciding upon the best treatment strategy in revision
arthroplasty, it is absolutely crucial to use the best possible preoperative
detection whether a periprosthetic joint infection (PJI) is present or not. New
molecular markers investigated in serum samples and synovial fluid can help to
improve the preoperative diagnosis. In 2001, a novel IL-6 lateral flow
immunoassay testing device was introduced which has never been tested in synovial
fluid so far. OBJECTIVE: For our study we investigated whether the test can be
used safely, feasibly and time effectively with synovial fluid gathered from
potentially infected THAs or TKAs and whether the already published cutoff for IL
6 in synovial fluid predicting a PJI can be reproduced using the QuickLine IL-6
immunoassay. METHODS: After ethic approval and within the scope of a prospective
controlled trial we investigated 26 patients (m = 9, 34.6%; f= 17, 65.4%) with n
= 13 (50%) potentially infected total hip arthroplasties (THAs) and n = 13 (50%)
suspected PJIs of total knee arthroplasties (TKAs). Sterile aspirated synovial
fluid was examined for total leukocyte count and cell differentiation by a blood
count analyzer in body fluid mode as well as for IL-6 (Immulite, Siemens Medical
Solutions Diagnostics GmbH, Eschborn, Germany). Another part of the joint
aspirate was tested using the QuickLine IL-6 Test by Milenia Biotec (Milenia
Biotec, Giebetaen, Germany). RESULTS: The mean concentration of IL-6 as
determined from our reference laboratory testing (Siemens Immulight) for aseptic
cases was 1,219 pg/mL (SD 1,369 pg/mL, min 134 pg/mL-max 4,214 pg/mL). The mean
IL-6 concentration measured via the IL-6 QuickLine for aseptic cases was 410
pg/mL (SD 371 pg/mL, min 100 pg/mL-max 1562 pg/mL). The test showed no false
negative or false positive results in the cases tested. In six patients, PJI was
considered proven. The QuickLine Test indicated IL 6 concentrations > 10,000
pg/mL in these cases without further quantification above this maximum detection
threshold. Results from the QuickLine Test and the laboratory tests were matched
and a non-linear best fit curve (log-log-curve) was applied. The subsequent
Spearman correlation showed a correlation coefficient of r = 0.92 (95% CI 0.81
0.97) which corresponds to a two-tailed p-value of < 0.0001, respectively. As a
primary finding we were able to show that the Milenia QuickLine IL-6 Test can be
used safely, feasibly and time effectively with synovial fluid gathered
intraoperatively from potentially infected THAs or TKAs. The test as provided
worked well in 84.6% of the samples tested and failed only due to very viscous
synovial fluid. As a secondary result we found that the previously published cut
off for IL-6 in synovial fluid predicting a PJI with a sensitivity of 46.88% and
a specificity of 97.62% can be reproduced using the QuickLine IL-6 immunoassay.
CONCLUSION: Taking the limitations of the low sample size as a given this
relatively simple point of care (POC) assay showed promising results in our pilot
trial and may help diagnosing PJI. It may help physicians and surgeons to choose
the best and least invasive treatment strategy for patients presenting with
painful arthroplasty.
PMID- 27497463
TI - Potential impact of oxygenators with venous air trap on air embolism in veno
arterial Extracorporeal Life Support.
AB - BACKGROUND: Air embolism is a potentially fatal but underrecognized complication
in Extracorporeal Life Support (ECLS). Oxygenators containing venous air traps
have been developed to minimize the risk of air embolism in daily care.
OBJECTIVE: We reproduced air embolism as occurring via a central venous catheter
in an experimental setting to test the potential of oxygenators with and without
venous bubble trap (VBT) to withhold air. METHODS: An in vitro ECLS circuit was
created and a central venous catheter with a 3-way stopcock and a perforated male
luer cap was inserted into the inflow line. Three different oxygenators with and
without VBT and their capability to withhold air were examined. After 60 seconds
of stable ECLS flow, the stopcock was opened towards the atmosphere for 3
minutes. Afterwards, air accumulation within the oxygenator was determined.
RESULTS: Comparison of the total air entrapment showed a significant superiority
of the oxygenators with VBT (p < 0.001). All oxygenators were able to partly
withhold macro air boli, however, the capacity of oxygenators with VBT was
higher. Passing through the oxygenator resulted in a reduction of microbubbles in
all cases. CONCLUSIONS: Macro air emboli can be substantially reduced by usage of
oxygenators that contain a VBT, whereas the capability to withhold microbubbles
to a vast extent seems to depend on the intrinsic oxygenator's membrane.
PMID- 27497464
TI - Rapid cross platform healthcare gaming design and implementation: The cost
effective methodology.
AB - There have been massive advances in E-Health and M-Health technology, with recent
interest in the utility of games for healthcare and the promotion of well-being
and recovery as well as patient empowerment. There has been various review
demonstrating the clinical effectiveness and efficacy of games for healthcare. It
is the aim of this technical note to illustrate how appropriate gaming engines
could be used by non-expert clinicians to program games that could run across
various platforms, as well as games that could integrate well with existing
mechanical sensors. This would address the limitations with regards to the
evidence base of games, as well as the limitations in the deployment of games to
various participants. More importantly, games designed are also more likely to be
cost-effective and lower in cost. The ability of integration with existing
mechanical sensors would value-add existing games and enable recovery and
remediation in various domains of health. This would further expand the potential
of games as an adjunctive treatment for patients, or at least, to maintain the
gains that they have made in their recovery process.
PMID- 27497465
TI - Erratum.
PMID- 27497466
TI - Unintentional injury after traumatic brain injury: Issues, assessment, and
reducing risk.
PMID- 27497467
TI - Using the public health model to address unintentional injuries and TBI: A
perspective from the Centers for Disease Control and Prevention (CDC).
AB - Traumatic brain injury (TBI) can have long term effects on mental and physical
health, and can disrupt vocational, educational, and social functioning. TBIs can
range from mild to severe and their effects can last many years after the initial
injury. CDC seeks to reduce the burden of TBI from unintentional injuries through
a focus on primary prevention, improved recognition and management, and
intervening to improve health outcomes after TBI. CDC uses a 4-stage public
health model to guide TBI prevention, moving from 1) surveillance of TBI, 2)
identification of risk and protective factors for TBI, 3) development and testing
of evidence-based interventions, to 4) bringing effective intervention to scale
through widespread adoption. CDC's unintentional injury prevention activities
focus on the prevention of sports-related concussions, motor vehicle crashes, and
older adult falls. For concussion prevention, CDC developed Heads Up - an
awareness initiative focusing on ways to prevent a concussion in sports, and
identifying how to recognize and manage potential concussions. In motor vehicle
injury prevention, CDC has developed a tool (MV PICCS) to calculate the expected
number of injuries prevented and lives saved using various evidence-based motor
vehicle crash prevention strategies. To help prevent TBI related to older adult
falls, CDC has developed STEADI, an initiative to help primary care providers
identify their patients' falls risk and provide effective interventions. In the
future, CDC is focused on advancing our understanding of the public health burden
of TBI through improved surveillance in order to produce more comprehensive
estimates of the public health burden of TBI.
PMID- 27497468
TI - Risk of hospitalization due to motor vehicle crashes among Iraq and Afghanistan
War Veterans diagnosed with traumatic brain injury.
AB - BACKGROUND: Traumatic brain injury (TBI) was deemed the 'signature injury' of the
Iraq and Afghanistan Wars (OEF/OIF/OND). Civilians with severe TBI have increased
risks of motor vehicle crashes (MVCs). Little is known about MVC risk among
Veterans with TBI, many of whom incurred TBIs that were mild in severity.
OBJECTIVE: To examine associations between TBI and MVC-related hospitalizations
among OEF/OIF/OND Veterans who use Veterans Health Administration (VA)
healthcare. METHODS: Using national VA data, we identified 277,330 Veterans who
enrolled in VA within one year of deployment. MVC, TBI, and other diagnoses were
identified using ICD-9-CM codes. We estimated risk of subsequent MVC
hospitalization for those with, versus without, TBI using time-to-event analyses.
Time-varying Cox proportional hazards models were used to compute hazard ratios
(HR) and 95% confidence intervals (CI) while controlling for potential
confounders, including psychiatric diagnoses. RESULTS: There were 28,551 Veterans
diagnosed with TBI; 130 were subsequently hospitalized for MVC. In adjusted
models, those with TBI were four times more likely to be hospitalized for MVC
than those without (HR = 4.2; CI = 3.3-5.3). CONCLUSION: Veterans with TBI had
substantially greater risk of MVC-related hospitalizations. These Veterans may
benefit from enhanced driving safety interventions to reduce risk.
PMID- 27497469
TI - Unintentional injuries after TBI: Potential risk factors, impacts, and
prevention.
AB - BACKGROUND: The top three causes of fatal unintentional injuries are falls, motor
vehicle crashes, and being struck against or struck by objects or persons. These
etiologies also happen to be the leading causes of TBI, a serious public health
problem, in the US. Reduced cognitive functioning, poor decision making,
increased risk taking, disinhibition, diminished safety skills and substance use,
place individuals with TBI at an increased risk for subsequent unintentional
injuries. The caregiving, psychological, social and financial burden of initial
injuries is enormous. Unintentional injuries post-TBI add to that burden
significantly. Many unintentional injuries can be prevented with simple education
and environment and lifestyle changes. Injury prevention requires collaboration
among many. OBJECTIVE: This literature review will share information regarding
potential triggers or causes of unintentional injuries after TBI to identify
potential issues. The many impacts of these injuries will be reviewed. Best
practices in prevention will be presented. CONCLUSION: Ultimately, education,
discussion, and awareness across multiple stakeholders can aid in preventing
unintentional injuries after TBI.
PMID- 27497470
TI - The Safety Assessment Measure for persons with traumatic brain injury: Item pool
development and content validity.
AB - BACKGROUND: Persons with moderate to severe TBI are at increased risk for
unintentional injury or harm in the home and community; however, there is
currently no standard measure of safety risk they face now and in the future.
OBJECTIVE: To develop comprehensive and content valid scales and item pools for
assessing safety and risk for persons with moderate to severe traumatic brain
injuries. METHOD: Qualitative psychometric methods for developing scales and
items were used including literature review, item development and revision, focus
groups with interdisciplinary rehabilitation staff (n = 26) for rating content
validity, and cognitive interviewing of TBI family members (n = 9) for assuring
item clarity. RESULTS: The Safety Assessment Measure is comprised of 6 primary
scales - Cognitive Capacity, Visuomotor Capacity, Wheelchair Use, Risk
Perception, Self-Regulation, and Compliance Failures with Safety Recommendations
in which family caregivers or clinicians rate the risk for unintentional injury
or harm in adults who have sustained moderate or severe TBI. The scale item pools
encompass a broad spectrum of everyday activities that pose risk in the home and
community and were rated as having excellent levels of content validity.
CONCLUSIONS: The Safety Assessment Measure scales and items cover a broad range
of instrumental activities of daily living that can increase the risk of
unintentional injuries or harm. Empirical evidence suggests that the Safety
Assessment Measure items have excellent content validity. Future research should
use modern psychometric methods to examine each scale unidimensionality, model
fit, and precision.
PMID- 27497472
TI - Differential transcriptional regulation by alternatively designed mechanisms: A
mathematical modeling approach.
AB - Cells maintain cellular homeostasis employing different regulatory mechanisms to
respond external stimuli. We study two groups of signal-dependent transcriptional
regulatory mechanisms. In the first group, we assume that repressor and activator
proteins compete for binding to the same regulatory site on DNA (competitive
mechanisms). In the second group, they can bind to different regulatory regions
in a noncompetitive fashion (noncompetitive mechanisms). For both competitive and
noncompetitive mechanisms, we studied the gene expression dynamics by increasing
the repressor or decreasing the activator abundance (inhibition mechanisms), or
by decreasing the repressor or increasing the activator abundance (activation
mechanisms). We employed delay differential equation models. Our simulation
results show that the competitive and noncompetitive inhibition mechanisms
exhibit comparable repression effectiveness. However, response time is fastest in
the noncompetitive inhibition mechanism due to increased repressor abundance, and
slowest in the competitive inhibition mechanism by increased repressor level. The
competitive and noncompetitive inhibition mechanisms through decreased activator
abundance show comparable and moderate response times, while the competitive and
noncompetitive activation mechanisms by increased activator protein level display
more effective and faster response. Our study exemplifies the importance of
mathematical modeling and computer simulation in the analysis of gene expression
dynamics.
PMID- 27497471
TI - Return to work after work-related traumatic brain injury.
AB - BACKGROUND: Work-related traumatic brain injury (wrTBI) comprises up to 24% of
TBIs, yet relatively little is known about it even though wrTBI incurs high costs
to employers, insurers, and injured. OBJECTIVES: To compare demographic,
clinical, and occupation-related factors following mild-to-moderate TBI of those
who successfully returned to work (RTW) versus those who did not, and to
determine perceived facilitators of and barriers to RTW. METHODS: Retrospective
cohort study from a consecutive sample of persons with TBI seen in an outpatient
assessment clinic. Surveys were mailed to eligible potential participants.
Consenting participants were interviewed by telephone or returned a completed
survey via mail. RESULTS: Fifty of 116 eligible individuals participated in the
study. Half of the participants returned to work. Participants in this group were
significantly younger and had more years of education than the no-RTW group. The
most common factors perceived to assist the RTW group were support of family and
friends (92%) and of treatment providers (80%), and employers who provided
accommodations (76%). Difficulty thinking and concentrating (94%) and fatigue
(94%) were the most common barriers to RTW. CONCLUSIONS: This study highlights
the importance of support from family, friends and employers as RTW facilitators.
These factors merit further investigation in TBI rehabilitation studies.
PMID- 27497473
TI - Cholesteryl Ester Transfer Protein Intimately Involved in Dyslipidemia-Related
Susceptibility to Cognitive Deficits in Type 2 Diabetic Patients.
AB - BACKGROUND: Cholesteryl ester transfer protein (CETP) is involved in diabetic
dyslipidemia. OBJECTIVE: We aim to test the hypothesis that CETP might be of
importance in mediating dyslipidemia-related susceptibility to cognitive deficits
in diabetic patients. METHODS: We recruited 190 type 2 diabetic patients and
divided them into two groups according to the Montreal Cognitive Assessment
(MoCA) score. The association between CETP and cognitive decline was analyzed
with logistic regression and stratification. RESULTS: There were 110 diabetic
patients with mild cognition impairment (MCI) and 80 healthy cognition subjects
as controls. Dyslipidemia is more common among diabetic patients with MCI; they
had a significant increase of serum CETP concentrations, which was negatively
correlated with MoCA (r = -0.638; p < 0.001). Negative correlations were also
found between the serum CETP concentration with the Auditory Verbal Learning Test
(r = -0.266; p = 0.008), indicating memory deficit. Logistic regression analysis
revealed that CETP concentration was an independent factor of diabetic MCI (p <
0.001). Further stratification study showed that high serum levels of CETP was an
independent risk factor of MCI in diabetic patients with a low density
lipoproteins level >=2.59 mmol/L, or high density lipoproteins level <=1.0 mmol/L
for men and <=1.3 mmol/L for women, or TG level >=1.7 mmol/L, after adjusting for
age, sex, education, and glucose control (all ps < 0.05). CONCLUSIONS: CETP was
intimately involved in dyslipidemia-related susceptibility to cognitive decline,
especially memory function in type 2 diabetic patients.
PMID- 27497474
TI - Cognitive Stimulation for People with Dementia in Long-Term Care Facilities:
Baseline Cognitive Level Predicts Cognitive Gains, Moderated by Depression.
AB - BACKGROUND: Increasing evidence demonstrates the efficacy of cognitive
stimulation (CS) in individuals with dementia. However, conducting studies in
nursing homes engenders specific challenges that have limited the data gathered
on this topic so far. OBJECTIVE: The aim of this randomized controlled trial was
to investigate the effects of CS on cognition, quality of life (QoL), behavioral
symptoms, and activities of daily life in persons with dementia living in nursing
homes. We further aimed to identify predictors of the intervention's benefits.
METHODS: Seventy-one persons with mild to moderate dementia were randomly
allocated to the experimental group (EG; n = 36) that visited a CS program twice
weekly for eight weeks or to the control group (CG; n = 35) that was receiving
usual care. Neuropsychological tests were conducted before and after the
intervention period and at six-week follow-up. RESULTS: There were no significant
interaction effects Time*Group for the outcome measures. However, regression
analysis revealed that a low cognitive baseline level predicted cognitive
improvements. Furthermore, a low baseline level of QoL predicted a QoL benefit.
For both findings, depression was a significant moderator, meaning that persons
with fewer depressive symptoms had a higher probability of showing improvements.
CONCLUSION: This study provides data on profiles of patients who are most likely
to profit from CS intervention in nursing-home settings and demonstrates that
treatment of depression is of the utmost relevance for a positive outcome of CS.
Living conditions will have to be considered more thoroughly in future research.
PMID- 27497475
TI - Late-Life Depressive Symptoms and Lifetime History of Major Depression: Cognitive
Deficits are Largely Due to Incipient Dementia rather than Depression.
AB - BACKGROUND: Late-life depression is frequently accompanied by cognitive
impairments. OBJECTIVE: Whether these impairments indicate a prodromal state of
dementia, or are a symptomatic expression of depression per se is not well
studied. METHODS: In a cohort of very old initially non-demented primary care
patients (n = 2,709, mean age = 81.1 y), cognitive performance was compared
between groups of participants with or without elevated depressive symptoms and
with or without subsequent dementia using ANCOVA (adjusted for age, sex, and
education). Logistic regression analyses were computed to predict subsequent
dementia over up to six years of follow-up. The same analytical approach was
performed for lifetime major depression. RESULTS: Participants with elevated
depressive symptoms without subsequent dementia showed only small to medium
cognitive deficits. In contrast, participants with depressive symptoms with
subsequent dementia showed medium to very large cognitive deficits. In adjusted
logistic regression models, learning and memory deficits predicted the risk for
subsequent dementia in participants with depressive symptoms. Participants with a
lifetime history of major depression without subsequent dementia showed no
cognitive deficits. However, in adjusted logistic regression models, learning and
orientation deficits predicted the risk for subsequent dementia also in
participants with lifetime major depression. CONCLUSION: Marked cognitive
impairments in old age depression should not be dismissed as "depressive
pseudodementia", but require clinical attention as a possible sign of incipient
dementia. Non-depressed elderly with a lifetime history of major depression, who
remained free of dementia during follow-up, had largely normal cognitive
performance.
PMID- 27497476
TI - FOXP2 Expression in Frontotemporal Lobar Degeneration-Tau.
AB - FOXP2 is altered in a variety of language disorders. We found reduced mRNA and
protein expression of FOXP2 in frontal cortex area 8 in Pick's disease, and
frontotemporal lobar degeneration-tau linked to P301L mutation presenting with
language impairment in comparison with age-matched controls and cases with
parkinsonian variant progressive supranuclear palsy. Foxp2 mRNA and protein are
also reduced with disease progression in the somatosensory cortex in transgenic
mice bearing the P301S mutation in MAPT when compared with wild-type littermates.
Our findings support the presence of FOXP2 expression abnormalities in sporadic
and familial frontotemporal degeneration tauopathies.
PMID- 27497477
TI - Breakdown of the Cerebrovasculature and Blood-Brain Barrier: A Mechanistic Link
Between Diabetes Mellitus and Alzheimer's Disease.
AB - Alzheimer's disease (AD) and diabetes mellitus (DM) are among the most pervasive
and devastating disorders that afflict people throughout the world. Although
typically associated with older demographics, recent epidemiologic studies have
reported parallel trends in decreasing age of onset and increasing incidence of
these conditions. Promising research continues to implicate the
cerebrovasculature and blood-brain barrier (BBB) as playing key roles in AD
pathoetiology. Similarly, complications accompanying DM, such as diabetic
nephropathy/retinopathy, cardiovascular disease, and stroke, have been rooted in
vascular compromise. Not surprisingly, DM is now considered a major risk factor
for AD. The purpose of this review is to highlight investigations into the role
of the cerebrovasculature in the development and progression of AD. We give
particular attention to studies on humans and a variety of animal model systems
that have demonstrated a link between BBB dysfunction and pathological changes in
the brain consistent with aging and AD. Together, these studies suggest that the
vascular complications associated with chronic, poorly managed DM can lead to
subclinical BBB breakdown that precedes and drives the pathological changes
progressing to symptomatic AD, providing a common mechanistic thread connecting
these two disorders. Furthermore, this emphasizes the need to focus on the
vasculature as a potential therapeutic target with the intent of limiting BBB
breakdown involved in disease initiation and progression. In conclusion, AD may
be more than just an associated comorbidity of DM, and instead another
manifestation of the underlying vascular pathology that is common to both.
PMID- 27497478
TI - Astrocytic GluN2A and GluN2B Oppose the Synaptotoxic Effects of Amyloid-beta1-40
in Hippocampal Cells.
AB - Early-stage Alzheimer's disease (AD) is characterized by synaptic dysfunction, a
phenomenon in which soluble oligomers of amyloid-beta (Abeta) and N-methyl-D
aspartate receptor (NMDAR) are implicated. Here, we demonstrated that astrocytes
express NMDARs and therefore have the potential to modulate the synaptotoxic
actions of Abeta. We found that specific pharmacological antagonism of two of the
major NMDAR subunits, GluN2A and GluN2B, exacerbates Abeta-induced
synaptotoxicity suggesting, for the first time, that astrocytic GluN2A and GluN2B
mediate synaptoprotection. From the perspective of the pathogenic mechanisms of
Alzheimer's disease, in which Abeta and NMDAR play significant roles, these
observations are striking since neuronal GluN2A and GluN2B are well known
modulators of neurodegeneration. We did initial studies to understand the basis
for the differential effects of astrocytic and neuronal GluN2A and GluN2B in the
promotion of synapse survival, and identified a neurotrophin produced by
astrocytes, nerve growth factor beta (beta-NGF), as a likely mediator of the
synaptoprotective effects of astrocytic GluN2A and GluN2B activation. The results
presented suggest that astrocytes may be suitable druggable targets for the
prevention and/or delay of the synaptic loss that occurs during early stages of
AD.
PMID- 27497479
TI - Adenosine Type A2A Receptor in Peripheral Cell from Patients with Alzheimer's
Disease, Vascular Dementia, and Idiopathic Normal Pressure Hydrocephalus: A
New/Old Potential Target.
AB - As the European population gets older, the incidence of neurological disorders
increases with significant impact on social costs. Despite differences in disease
etiology, several brain disorders in the elderly (e.g., Alzheimer's disease,
vascular dementia, normal pressure hydrocephalus) share dementia as a common
clinical feature. The current treatment for the majority of these diseases is
merely symptomatic and does not modify the course of the illness. Symptoms of
normal pressure hydrocephalus are the only ones that can be modified if they are
recognized in time and treated appropriately. Therefore, an important clinical
strategy may be disclosed by pathogenic pathways that can be modified and to find
drugs that can slow down or even arrest disease progression. Possibly a way to
answer this question could be by re-examining all the molecules which have so far
succeeded in improving many aspects of cognitive deterioration in some
neurodegenerative conditions, that were not considered because of controversial
opinions. The main purpose of this summary is to further substantiate the
hypothesis that the pathway of adenosine type A2A receptor could be used as a
potential target to develop new/old therapeutic strategies.
PMID- 27497480
TI - Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation
and Improves Memory Function in Adult Mice.
AB - Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could
trigger cognitive dysfunction and increase the risk of dementia including
Alzheimer's disease (AD). The present study was undertaken in order to examine
whether B vitamins (B6, B12, folate, and choline) could exert protective effects
on hypoxia-induced memory deficit and AD related molecular events in mice. Adult
male Kunming mice were assigned to five groups: normoxic control, hypoxic model
(HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin
B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were
exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber
mimicking 5500 meters of high altitude. Spatial and passive memories were
assessed by radial arm and step-through passive test, respectively. Levels of tau
and glycogen synthase kinase (GSK)-3beta phosphorylation were detected by western
blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling
assay. Mice in the HH group exhibited significant spatial working and passive
memory impairment, increased tau phosphorylation at Thr181, Ser262,
Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels
compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK
3beta were significantly decreased in brain after hypoxic treatment.
Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate
the hypoxia-induced memory deficits, observably decreased Hcy concentrations in
serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related
sites through upregulating inhibitory Ser9-phosphorylated GSK-3beta. Our finding
give further insight into combined neuroprotective effects of vitamin B6, B12,
folate, and choline on brain against hypoxia.
PMID- 27497481
TI - Tau in Late-Life Depression: A Systematic Review and Meta-Analysis.
AB - A lifetime history of major depressive disorder (MDD) increases the risk of
developing Alzheimer's disease, of which neurofibrillary tangles due to abnormal
tau proteins are a hallmark. We systematically reviewed the literature on tau in
MDD and identified 49 relevant articles spanning a number of modalities,
including cerebrospinal fluid (CSF) analysis, positron emission tomography, and
clinicopathological correlation. We compared CSF total and phosphorylated tau
proteins in MDD and controls using a meta-analytic approach. We found no
difference in total or phosphorylated tau in MDD. We also found no difference in
a comparison of a subgroup excluding studies with significant age differences.
Positron emission tomography studies lacked specificity. Clinicopathological
studies failed to associate neurofibrillary tangles with MDD. The available data
on tau in MDD is limited. The involvement of tau in a subset of MDD cannot be
ruled out and requires prospective exploration.
PMID- 27497482
TI - Yokukansan in the Treatment of Behavioral and Psychological Symptoms of Dementia:
An Updated Meta-Analysis of Randomized Controlled Trials.
AB - BACKGROUND: Previous clinical studies found that yokukansan has a therapeutic
effect on behavioral and psychological symptoms of dementia (BPSD) in dementia
patients. OBJECTIVE: To perform an updated meta-analysis of randomized controlled
trials (RCTs) testing yokukansan for patients with BPSD. METHODS: Primary
efficacy and safety endpoints were BPSD total scores and all-cause
discontinuation, respectively. Secondary outcomes were BPSD subscales, cognitive
function scores [Mini-mental state examination (MMSE)], activities of daily
living (ADL) scores, discontinuation due to adverse events (AEs), and incidences
of AEs. RESULTS: Five RCTs with 381 patients with BPSD were included. Compared
with controls [placebo+usual care (UC)], yokukansan significantly decreased BPSD
total scores [standardized mean difference (SMD) = -0.32, 95% confidence interval
(CI) = -0.53 to -0.11, p = 0.003, I2 = 0%, N = 5 studies, n = 361]. Yokukansan
was more efficacious in reducing BPSD subscale scores (delusions: SMD = -0.51,
95% CI = -0.98 to -0.04, hallucinations: SMD = -0.54, 95% CI = -0.96 to -0.12,
agitation/aggression: SMD = -0.37, 95% CI = -0.60 to -0.15) than placebo+UC.
However, yokukansan was not superior to placebo+UC for BPSD total as well as any
subscales scores only in Alzheimer's disease patients. Compared with UC,
yokukansan treatment improved ADL scores (SMD = -0.32, 95% CI = -0.62 to -0.01).
MMSE scores did not differ between the yokukansan and placebo+UC treatment
groups. No significant differences were found in all-cause discontinuation,
discontinuation due to AEs, and incidences of AEs between yokukansan and
placebo+UC treatments. CONCLUSIONS: Our results suggest that yokukansan is
beneficial for the treatment of patients with BPSD and is well-tolerated; it was
not beneficial for BPSD total and any subscale scores only in Alzheimer's disease
patients.
PMID- 27497483
TI - Cerebral Arterial Occlusion Did Not Promote the Prevalence of Cerebral Amyloid
Angiopathy.
AB - BACKGROUND: An impairment of amyloid-beta (Abeta) clearance has been suggested in
Alzheimer's disease. Perivascular drainage along cerebrovascular vessels is
considered an important amyloid clearance pathway. OBJECTIVE: This study examined
the effect of reduced arterial pulsation that could cause an impairment in
cerebral amyloid drainage on the prevalence of cortical microbleeds (CMBs), a
surrogate marker for cerebral amyloid angiopathy (CAA). METHODS: Patients who
lost depiction of either side of the carotid artery or the middle cerebral artery
on magnetic resonance angiography were studied. Those who showed acute cerebral
infarction or a previous cortical cerebral infarction were excluded. The number
of CMBs was counted on the occluded and non-occluded sides of the brain in each
subject. The number of subjects who showed more CMBs on the occluded side of the
brain was compared with the number of subjects who showed more CMBs on the non
occluded side of the brain. RESULTS: Twenty-eight patients were studied. The
extent of lacunar infarction and white matter lesions was not different,
irrespective of the occluded vessels or the distribution of CMBs. The prevalence
of CMBs was not different between the occluded and non-occluded sides of the
brain. CONCLUSION: In this cross-sectional study, reduction of arterial pulsation
was not associated with a higher prevalence of CAA. Therefore, reduced arterial
pulsation alone may not be enough to promote CAA.
PMID- 27497484
TI - Herpes and Alzheimer's Disease: Subversion in the Central Nervous System and How
It Might Be Halted.
AB - The last 8 or so years have seen a large increase in the number of studies
supporting the concept of a major role for herpes simplex virus type 1 (HSV1) in
Alzheimer's disease (AD). The main advances have been made through studies in
humans and in mice, investigating the likelihood of reactivation of the latent
virus in brain. Others have aimed to explain the mechanisms in cells whereby the
increase in amyloid-beta (Abeta) production on HSV1 infection of cells and mouse
brains occurs, and the reason that infected cells make this increase. The
possibility that other herpesviruses are involved in the development of AD has
been explored, and human herpesvirus type 6, Epstein-Barr virus, and
cytomegalovirus, in particular, have been implicated. Epidemiological studies
have further supported the role specifically of HSV1 and its reactivation in the
disease. Antiviral studies have continued, comparing those acting by different
mechanisms, such as restricting viral replication, or blocking viral entry into
cells, to treat HSV1-infected cell cultures, and then examining the extent to
which the virus-induced increases in Abeta and AD-like tau are reduced. All the
studies support the usage of antiviral treatment to slow or halt the progression
of AD.
PMID- 27497486
TI - Is Axonal Degeneration a Key Early Event in Parkinson's Disease?
AB - Recent research suggests that in Parkinson's disease the long, thin and
unmyelinated axons of dopaminergic neurons degenerate early in the disease
process. We organized a workshop entitled 'Axonal Pathology in Parkinson's
disease', on March 23rd, 2016, in Cleveland, Ohio with the goals of summarizing
the state-of-the-art and defining key gaps in knowledge. A group of eight
research leaders discussed new developments in clinical pathology, functional
imaging, animal models, and mechanisms of degeneration including
neuroinflammation, autophagy and axonal transport deficits. While the workshop
focused on PD, comparisons were made to other neurological conditions where
axonal degeneration is well recognized.
PMID- 27497487
TI - Brain networks under attack: robustness properties and the impact of lesions.
AB - A growing number of studies approach the brain as a complex network, the so
called 'connectome'. Adopting this framework, we examine what types or extent of
damage the brain can withstand-referred to as network 'robustness'-and
conversely, which kind of distortions can be expected after brain lesions. To
this end, we review computational lesion studies and empirical studies
investigating network alterations in brain tumour, stroke and traumatic brain
injury patients. Common to these three types of focal injury is that there is no
unequivocal relationship between the anatomical lesion site and its topological
characteristics within the brain network. Furthermore, large-scale network
effects of these focal lesions are compared to those of a widely studied
multifocal neurodegenerative disorder, Alzheimer's disease, in which central
parts of the connectome are preferentially affected. Results indicate that human
brain networks are remarkably resilient to different types of lesions, compared
to other types of complex networks such as random or scale-free networks.
However, lesion effects have been found to depend critically on the topological
position of the lesion. In particular, damage to network hub regions-and
especially those connecting different subnetworks-was found to cause the largest
disturbances in network organization. Regardless of lesion location, evidence
from empirical and computational lesion studies shows that lesions cause
significant alterations in global network topology. The direction of these
changes though remains to be elucidated. Encouragingly, both empirical and
modelling studies have indicated that after focal damage, the connectome carries
the potential to recover at least to some extent, with normalization of graph
metrics being related to improved behavioural and cognitive functioning. To
conclude, we highlight possible clinical implications of these findings, point
out several methodological limitations that pertain to the study of brain
diseases adopting a network approach, and provide suggestions for future
research.
PMID- 27497489
TI - Reply: Glial mitochondropathy in infantile neuroaxonal dystrophy:
pathophysiological and therapeutic implications.
PMID- 27497488
TI - Healthy brain connectivity predicts atrophy progression in non-fluent variant of
primary progressive aphasia.
AB - Neurodegeneration has been hypothesized to follow predetermined large-scale
networks through the trans-synaptic spread of toxic proteins from a syndrome
specific epicentre. To date, no longitudinal neuroimaging study has tested this
hypothesis in vivo in frontotemporal dementia spectrum disorders. The aim of this
study was to demonstrate that longitudinal progression of atrophy in non
fluent/agrammatic variant primary progressive aphasia spreads over time from a
syndrome-specific epicentre to additional regions, based on their connectivity to
the epicentre in healthy control subjects. The syndrome-specific epicentre of the
non-fluent/agrammatic variant of primary progressive aphasia was derived in a
group of 10 mildly affected patients (clinical dementia rating equal to 0) using
voxel-based morphometry. From this region, the inferior frontal gyrus (pars
opercularis), we derived functional and structural connectivity maps in healthy
controls (n = 30) using functional magnetic resonance imaging at rest and
diffusion-weighted imaging tractography. Graph theory analysis was applied to
derive functional network features. Atrophy progression was calculated using
voxel-based morphometry longitudinal analysis on 34 non-fluent/agrammatic
patients. Correlation analyses were performed to compare volume changes in
patients with connectivity measures of the healthy functional and structural
speech/language network. The default mode network was used as a control network.
From the epicentre, the healthy functional connectivity network included the left
supplementary motor area and the prefrontal, inferior parietal and temporal
regions, which were connected through the aslant, superior longitudinal and
arcuate fasciculi. Longitudinal grey and white matter changes were found in the
left language-related regions and in the right inferior frontal gyrus. Functional
connectivity strength in the healthy speech/language network, but not in the
default network, correlated with longitudinal grey matter changes in the non
fluent/agrammatic variant of primary progressive aphasia. Graph theoretical
analysis of the speech/language network showed that regions with shorter
functional paths to the epicentre exhibited greater longitudinal atrophy. The
network contained three modules, including a left inferior frontal
gyrus/supplementary motor area, which was most strongly connected with the
epicentre. The aslant tract was the white matter pathway connecting these two
regions and showed the most significant correlation between fractional anisotropy
and white matter longitudinal atrophy changes. This study showed that the pattern
of longitudinal atrophy progression in the non-fluent/agrammatic variant of
primary progressive aphasia relates to the strength of connectivity in pre
determined functional and structural large-scale speech production networks.
These findings support the hypothesis that the spread of neurodegeneration occurs
by following specific anatomical and functional neuronal network architectures.
PMID- 27497490
TI - Glial mitochondropathy in infantile neuroaxonal dystrophy: pathophysiological and
therapeutic implications.
PMID- 27497492
TI - Centre of epileptogenic tubers generate and propagate seizures in tuberous
sclerosis.
AB - SEE DUCHOWNY DOI101093/AWW216 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE:
Multiple seizure foci, seizure propagation and epileptic spasms complicate
presurgical seizure localization in tuberous sclerosis. Furthermore, controversy
exists about the contribution of tubers, perituberal cortex and the underlying
genetic abnormality to epileptogenesis. We aimed to determine the epileptogenic
substrate in tuberous sclerosis by studying spatio-temporal patterns of seizure
onset and propagation on intracranial EEG recordings in which multiple depth and
surface electrodes sampled multiple tubers and perituberal cortex. Ten
intracranial EEG recordings (seven extraoperative, three intraoperative) from 10
children with tuberous sclerosis were analysed. Notable thickening and signal
abnormality in the centre of many tubers on magnetic resonance imaging led to
tuber centres being recorded with depth electrodes. Spatially-meaningful bipolar
montages were reformatted incorporating channels recording only from the tuber
centre, tuber rim and perituberal cortex. Interictal epileptiform discharges and
ictal rhythms were analysed visually for location, field, morphology, frequency,
latency and temporal dispersion. Fifteen electroclinically distinct seizures were
recorded in the 10 patients. Seizure onset was recorded in tubers in all 15
electroclinically distinct seizures; in 9/10 electroclinically distinct seizures
recorded with optimal spatial sampling, seizure onset was recorded in the tuber
centre, with or without involvement of the tuber rim but not perituberal cortex.
Quantitative electroencephalography analysis by pairwise cross-correlation
confirmed that the tuber centre led the tuber rim and perituberal cortex during
interictal, preictal and ictal spike trains. Seizure propagation was observed in
10/15 electroclinically distinct seizures, being tuber-to-tuber in all. Seven of
the 17 tubers showing seizure propagation activated an independent ictal rhythm,
morphologically distinct from that seen in seizure onset region (intra-ictal
activation). Of the total 48 tubers sampled, 16 exhibited seizure onset, 17 were
involved in seizure propagation and 40 exhibited interictal epileptiform
discharges, 33 independent and seven propagated. Seizure onsets were recorded in
16/33 tubers with independent interictal epileptiform discharges, but 0/7 tubers
with only propagated epileptiform discharges or 0/8 tubers with no epileptiform
discharges (P = 0.003). Seizure onsets were recorded from 4/7 tubers with and
0/10 tubers without intra-ictal activation (P = 0.015). Thus, focal seizures and
interictal epileptiform discharges in tuberous sclerosis arise in the centre of
epileptogenic tubers and propagate to the tuber rim, perituberal cortex and other
epileptogenic tubers. Rhythmic interictal epileptiform discharges and intra-ictal
activation of propagated ictal rhythms are potential biomarkers of epileptogenic
tubers. Interictal and ictal EEG features of epileptogenic tubers have
similarities to focal cortical dysplasia type II, consistent with the reported
imaging, histological and molecular similarities.
PMID- 27497491
TI - Delayed seizures after intracerebral haemorrhage.
AB - Late seizures after intracerebral haemorrhage occur after the initial acute
haemorrhagic insult subsides, and represent one of its most feared long-term
sequelae. Both susceptibility to late seizures and their functional impact remain
poorly characterized. We sought to: (i) compare patients with new-onset late
seizures (i.e. delayed seizures), with those who experienced a recurrent late
seizure following an immediately post-haemorrhagic seizure; and (ii) investigate
the effect of late seizures on long-term functional performance after
intracerebral haemorrhage. We performed prospective longitudinal follow-up of
consecutive intracerebral haemorrhage survivors presenting to a single tertiary
care centre. We tested for association with seizures the following neuroimaging
and genetic markers of cerebral small vessel disease: APOE variants
epsilon2/epsilon4, computer tomography-defined white matter disease, magnetic
resonance imaging-defined white matter hyperintensities volume and cerebral
microbleeds. Cognitive performance was measured using the Modified Telephone
Interview for Cognitive Status, and functional performance using structured
questionnaires obtained every 6 months. We performed time-to-event analysis using
separate Cox models for risk to develop delayed and recurrent seizures, as well
as for functional decline risk (mortality, incident dementia, and loss of
functional independence) after intracerebral haemorrhage. A total of 872
survivors of intracerebral haemorrhage were enrolled and followed for a median of
3.9 years. Early seizure developed in 86 patients, 42 of whom went on to
experience recurrent seizures. Admission Glasgow Coma Scale, increasing haematoma
volume and cortical involvement were associated with recurrent seizure risk (all
P < 0.01). Recurrent seizures were not associated with long-term functional
outcome (P = 0.67). Delayed seizures occurred in 37 patients, corresponding to an
estimated incidence of 0.8% per year (95% confidence interval 0.5-1.2%). Factors
associated with delayed seizures included cortical involvement on index
haemorrhage (hazard ratio 1.63, P = 0.036), pre-haemorrhage dementia (hazard
ratio 1.36, P = 0.044), history of multiple prior lobar haemorrhages (hazard
ratio 2.50, P = 0.038), exclusively lobar microbleeds (hazard ratio 2.22, P =
0.008) and presence of >= 1 APOE epsilon4 copies (hazard ratio 1.95, P = 0.020).
Delayed seizures were associated with worse long-term functional outcome (hazard
ratio 1.83, P = 0.005), but the association was removed by adjusting for
neuroimaging and genetic markers of cerebral small vessel disease. Delayed
seizures after intracerebral haemorrhage are associated with different risk
factors, when compared to recurrent seizures. They are also associated with worse
functional outcome, but this finding appears to be related to underlying small
vessel disease. Further investigations into the connections between small vessel
disease and delayed seizures are warranted.
PMID- 27497493
TI - Nuclear trafficking in amyotrophic lateral sclerosis and frontotemporal lobar
degeneration.
AB - Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are two ends
of a phenotypic spectrum of disabling, relentlessly progressive and ultimately
fatal diseases. A key characteristic of both conditions is the presence of TDP-43
(encoded by TARDBP) or FUS immunoreactive cytoplasmic inclusions in neuronal and
glial cells. This cytoplasmic mislocalization of otherwise predominantly nuclear
RNA binding proteins implies a perturbation of the nucleocytoplasmic shuttling as
a possible event in the pathogenesis. Compromised nucleocytoplasmic shuttling has
recently also been associated with a hexanucleotide repeat expansion mutation in
C9orf72, which is the most common genetic cause of amyotrophic lateral sclerosis
and frontotemporal lobar degeneration, and leads to accumulation of cytoplasmic
TDP-43 inclusions. Mutation in C9orf72 may disrupt nucleocytoplasmic shuttling on
the level of C9ORF72 protein, the transcribed hexanucleotide repeat RNA, and/or
dipeptide repeat proteins translated form the hexanucleotide repeat RNA. These
defects of nucleocytoplasmic shuttling may therefore, constitute the common
ground of the underlying disease mechanisms in different molecular subtypes of
amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
PMID- 27497494
TI - Morphological and neuroanatomical study of the mammary gland in the immature and
mature European beaver (Castor fiber).
AB - This study investigated general morphology and immunohistochemical properties of
nerve fibres supplying the mammary gland (MG) in the European beaver. The
microscopic analysis of the beaver mammary gland revealed the presence of
morphological structures which are characteristic for mammals. There were no
distinct differences in the morphological features of the mammary gland between
the juvenile and non-pregnant mature beaver. The nerve fibres were visualized
using antibodies against protein gene product 9.5 (PGP) and biologically active
substances including beta-hydroxylase tyrosine (DbetaH), neuropeptide Y (NPY),
calcitonine gene-related peptide (CGRP) and substance P (SP). The study has
revealed that the MG in the juvenile and mature beaver is richly supplied with
PGP-immunoreactive (PGP-IR) nerve fibres. The most abundant innervation was
observed in the nipple and less numerous nerve terminals supplied the glandular
tissue. Double-labelling immunohistochemistry disclosed that the majority of PGP
IR nerve fibres associated with blood vessels and smooth muscle cells in both the
nipple and glandular tissue were also DbetaH-IR. However, these nerve terminals
were less numerous in the glandular tissue than in the nipple. Most of the DbetaH
IR axons associated with arteries and smooth muscle cells in the entire gland
also stained for NPY. Small number of DbetaH/NPY-IR fibres supplied veins. CGRP
IR fibres were more abundant than those expressing SP. No distinct differences in
the distribution and immunohistochemical characteristic of nerve fibres were
observed between the juvenile and adult animals. The distribution and
immunohistochemical properties of nerve fibres supplying the gland in the beaver
remind those previously described in other mammalian species.
PMID- 27497496
TI - Letter to the Editor: Surgical versus conservative management of congenital
pulmonary airway malformation in children: A systematic review and meta-analysis"
by Kapralik et al J Pediatr Surg 51 (2016) 508-512.
PMID- 27497495
TI - Outcomes of arterial vascular extremity trauma in pediatric patients.
AB - BACKGROUND: Vascular trauma in children, although rare, carries significant risk
for repair. Here we report outcomes from a single trauma center for children with
extremity vascular trauma, proximal to the digits. METHODS: Retrospective chart
review of patients less than age 18years with an acute, non-iatrogenic traumatic
arterial vascular injury of the upper and/or lower extremity between January 2008
and December 2013. Abstracted patient demographics, injury characteristics,
surgical management, and disposition were summarized and compared with
nonparametric methods. RESULTS: 23 children comprised the study cohort: median
age of 8years (IQR: 4.6-12), 61% (n=14) males, 100% survival. Penetrating
injuries were the predominate mechanism (n=17, 74%). The median time to
presentation was 154min (IQR: 65-330). Acute operations for revascularization
included a primary repair (n=15, 65%) or reversed vein graft (n=7, 30%).
Fasciotomies were done for 3 (13%) patients. Three amputations were done for
failed revascularization. Upper extremity vascular injury (n=15, 65%) was more
common. The rate of associated extremity fracture was similar between upper (21%)
and lower (33%) extremities (p=0.643). Eight (35%) patients required additional
surgery most commonly for debridement, washouts and dressing changes. Three
patients' hospital stays were complicated by infection. Impaired function was the
most common short- and long-term complication (60%, 75%). CONCLUSION: Pediatric
vascular injuries are commonly associated with penetrating injuries and male
gender and occurred more frequently in the upper extremities. Overall patency
rates after repair were 87%. Fasciotomies were done in 13% of patients, and the
overall surgical amputation rate was 13%. There was no mortality in this cohort;
however, multiple operations are commonly required, including the return to OR
for washouts, debridements and dressing changes. The most common short- and long
term complication was impaired function. Overall good results are achievable in
pediatric vascular trauma treated with revascularization.
PMID- 27497497
TI - The lost art of the splenorrhaphy.
AB - BACKGROUND: In the case of the hemodynamically unstable child, splenorrhaphy is
preferred to splenectomy to avert postsplenectomy sepsis. However, successful
splenorrhaphy requires familiarity with the procedure. We sought to determine how
many splenectomies or splenorrhaphies for trauma the average pediatric surgeon
can be expected to perform during their career. METHODS: The Pediatric Health
Information System (PHIS) Database was queried for patients <=18years coded with
an International Classification of Diseases 9th Edition diagnosis code of a
splenic injury from 2004 to 2013. Age, gender, grade of splenic injury, and
operations performed were extracted. Numbers of pediatric surgeons per hospital
were obtained. RESULTS: 9567 children were identified. 2.1% underwent a
splenectomy and 0.8% underwent a splenorrhaphy. The average surgeon performed 0.6
(SD=0.6) splenectomies and 0.2 (SD=0.4) splenorrhaphies for trauma. If these
rates remain constant over time, the average surgeon would perform 1.8 (SD =1.7)
splenectomies and 0.6 (SD =1.1) splenorrhaphies for trauma over a 30-year
surgical career. CONCLUSION: Nonoperative management is associated with a host of
benefits, but has resulted in a decrease in the experience level of the pediatric
surgeons expected to perform an emergency splenectomy or splenorrhaphy when the
unusual occasion arises.
PMID- 27497498
TI - [Are cancer outpatients ready for e-medicine?]
AB - INTRODUCTION: E-health offers new opportunities for improving cancer outpatients'
monitoring. The aim of this study was to assess the level and the use of
electronic communication tools owned by cancer outpatients currently undergoing
antitumoral treatment. METHODS: This observational study consecutively recruited
patients undergoing treatment at two day hospital oncology units from 1st to 31
October 2015. Each patient completed one standardised, anonymous questionnaire.
RESULTS: Overall, 386 questionnaires were analysed, of which 244 and 142 patients
were from each hospital. Of these patients, 73% had access to the Internet either
directly or through a third party. More than 90% of the patients owned a mobile
phone, and half of them had a smartphone with Internet access. An increasing age
and the socioeconomic class level were significantly associated with the use of
the Internet and of a smartphone. Half of the patients had accessed websites
dedicated to health topics and a quarter had used mobile applications on health
topics. One-third of those patients found these electronic tools helpful. After
adjustment, an increasing age was significantly associated with a decreased use
of such tools. The majority (87%) of the patients enjoyed receiving text message
reminders from their hospital about their consultation schedule. CONCLUSION:
Three in four cancer outpatients under treatment have access to the Internet and
half use websites dedicated to health topics, with an impact of the age and the
socioeconomic class level. Developing e-communication tools between caregivers
and patients might be considered to improve their home monitoring.
PMID- 27497499
TI - Bandwidth and sample rate requirements for wearable head impact sensors.
AB - Wearable inertial sensors measure human head impact kinematics important to the
on-going development and validation of head injury criteria. However, sensor
specifications have not been scientifically justified in the context of the
anticipated field impact dynamics. The objective of our study is to determine the
minimum bandwidth and sample rate required to capture the impact frequency
response relevant to injury. We used high-bandwidth head impact data as ground
truth measurements, and investigated the attenuation of various injury criteria
at lower bandwidths. Given a 10% attenuation threshold, we determined the minimum
bandwidths required to study injury criteria based on skull kinematics and brain
deformation in three different model systems: helmeted cadaver (no neck),
unhelmeted cadaver (no neck), and helmeted dummy impacts (with neck). We found
that higher bandwidths are required for unhelmeted impacts in general and for
studying strain rate injury criteria. Minimum gyroscope bandwidths of 300Hz in
helmeted sports and 500Hz in unhelmeted sports are necessary to study strain rate
based injury criteria. A minimum accelerometer bandwidth of 500Hz in unhelmeted
sports is necessary to study most injury criteria. Current devices typically
sample at 1000Hz, with gyroscope bandwidths below 200Hz, which are not always
sufficient according to these requirements. With hard contact test conditions,
the identified requirements may be higher than most soft contacts on the field,
but should be satisfied to capture the worst contact, and often higher risk,
scenarios relative to the specific sport or activity. Our findings will help
establish standard guidelines for sensor choice and design in traumatic brain
injury research.
PMID- 27497500
TI - Cost-effective (gaming) motion and balance devices for functional assessment:
Need or hype?
AB - In the last decade, technological advances in the gaming industry have allowed
the marketing of hardware for motion and balance control that is based on
technological concepts similar to scientific and clinical equipment. Such
hardware is attractive to researchers and clinicians for specific applications.
However, some questions concerning their scientific value and the range of future
potential applications have yet to be answered. This article attempts to present
an objective analysis about the pros and cons of using such hardware for
scientific and clinical purposes and calls for a constructive discussion based on
scientific facts and practical clinical requests that are emerging from
application fields.
PMID- 27497501
TI - Modeling female and male rib geometry with logarithmic spirals.
AB - In this study we present a novel six-parameter shape model of the human rib
centroidal path using logarithmic spirals. It provides a reduction in parameter
space from previous models of overall rib shape, while simultaneously reducing
fitting error by 34% and increasing curvature continuity. Furthermore, the model
directly utilizes geometric properties such as rib end-to-end span, aspect ratio,
rib "skewness", and inner angle with the spine in its parameterization, making
the effects of each parameter on overall shape intuitive and easy to visualize.
The model was tested against 2197 rib geometries extracted from CT scans from a
population of 100 adult females and males of uniformly distributed ages between
20 and 70. Significant size and shape differences between genders were
identified, and shape model utility is demonstrated by the production of
statistically average male and female rib shapes for all rib levels. Simulated
mechanical loading of the resulting model rib shapes showed that the stiffness of
statistically average male and female ribs matched well with the average rib
stiffness from each separate population. This in-plane rib shape model can be
used to characterize variation in human rib geometry seen throughout the
population, including investigation of the overall changes in shape and resultant
mechanical properties that ribs undergo during aging or disease progression.
PMID- 27497502
TI - Flow characteristics around proximal and distal stenoses in a series of tandem
stenosed vessels.
AB - The flow characteristics around the proximal and distal stenoses in tandem vessel
models are experimentally investigated with varying flow rates (Q=0.25, 0.5,
1.0L/min), interspacing distances (L=3, 6, 10 of diameter D) and severities
(S=50%, 75% reduction in diameter). When the interspacing L is larger than 10 D,
no fluid-dynamic interaction is observed. The flow between the proximal and
distal stenoses becomes stabilized (turbulence intensity of <3%) as the
interspacing distance decreases. When the severity S is 75%, the transition from
laminar to turbulent flow occurs at a flow rate higher than 0.5L/min, although
the interspacing distance L is 3 D. Formation of recirculation flow is restricted
by the presence of distal stenosis as the interspacing distance decreases. In
this case, the flow between the stenoses is focused on the central region. The
center-line velocity at the neck of the distal stenosis is approximately 10-15%
higher than that of the proximal stenosis with equal severity of S=50%. When the
inlet flow is center-focused, the lengths of the recirculation and the jet core
behind the distal stenosis increase with decrease in interspacing distance L.
When the inlet flow is turbulent, the transition from laminar to turbulent flow
occurs early as the interspacing distance L is reduced. When the upstream
proximal stenosis exhibits increased severity, the pressure drop is measured to
be 20% compared with that when the severity of the downstream distal stenosis is
increased at the flow rate of Q=1.0L/min.
PMID- 27497503
TI - Nephroureteral Obstructions: The Use of Stents and Ureteral Bypass Systems for
Renal Decompression.
AB - Canine and feline nephroureteral obstruction is a complex disease process that
can be challenging to treat. Although the availability of various imaging
modalities allows for a straightforward diagnosis to be made in most cases, the
decision-making process for when a case should be taken to surgery and the
optimal treatment modality that should be used for renal decompression remains
controversial. In the following discussion, an overview of the perioperative
management of cases with nephroureterolithiasis and nephroureteral obstruction is
reviewed, with particular focus on the use of renal decompressive procedures,
such as ureteral stenting and subcutaneous ureteral bypass system placement.
PMID- 27497504
TI - Statin Intolerance: A Literature Review and Management Strategies.
AB - Statin intolerance is a commonly encountered clinical problem for which useful
management strategies exist. Although many patients report statin-related muscle
symptoms, studies indicate that the majority of these patients can tolerate a
statin upon re-challenge. Alternative statin dosing strategies are an effective
way to modify and reintroduce statin therapy for patients reporting adverse
symptoms. Correction of vitamin D deficiency and hypothyroidism may improve
statin tolerability in some patients. CoQ10 supplementation has been found to be
of no benefit for statin-related muscle symptoms in most recent clinical trials.
PCSK9 inhibitors are a new therapeutic option that if confirmed as safe and
effective by outcomes trials may be of substantial benefit to select patients at
high ASCVD risk who are unable to achieve adequate low-density lipoprotein
cholesterol (LDL-C) lowering on maximally tolerated statin therapy. Other
available medications to lower LDL-C in statin intolerant patients include
ezetimibe, bile acid sequestrants, niacin, and fibrates.
PMID- 27497505
TI - Metabolic Syndrome: An Evolving Clinical Construct.
AB - Metabolic syndrome (MetS), a clustering of metabolic risk factors, identifies
individuals at increased risk of diabetes and cardiovascular disease (CVD).
Measurement of waist circumference, high-density lipoprotein-cholesterol,
triglycerides, blood pressure and fasting blood glucose are easily obtained in
the clinic. At any level of low-density lipoprotein-cholesterol, presence of MetS
increases the risk of adverse CVD outcomes including bothatherosclerotic CVD and
atrial fibrillation. The MetS construct should focus the clinician on
recommending behavioral lifestyle modification as this improves all of its
components. The challenge, however, has been the lack of a standardized approach
to achieve effective and sustained lifestyle modification in clinical practice.
We briefly review various approaches useful to the clinician in counseling such
patients. These include group lifestyle programs and emerging mobile technology.
Technology alone may not be sufficient, but as an adjunct has the promise to
improve low rates of behavioral change currently seen with traditional programs.
PMID- 27497506
TI - The re-emergence of lipoprotein(a) in a broader clinical arena.
AB - Lipoprotein(a) [Lp(a)] is a genetic, independent and likely causal risk factor
for cardiovascular disease (CVD) and calcific aortic valve stenosis (CAVS). Lp(a)
levels are primarily genetically determined and tend to fluctuate only mildly
around a pre-determined level. In primary care settings, one Lp(a) measurement
can reclassify up to 40% of patients in intermediate risk score categories. In
secondary care settings, recent data from the JUPITER and AIM-HIGH trials
demonstrate that elevated Lp(a) remains part of the "residual risk" despite
achievement of low-density lipoprotein cholesterol levels <70 mg/dL. Recent
reports suggest that statins can increase Lp(a) levels, potentially further
contributing to this residual risk. Current therapies to lower Lp(a) are limited
to niacin, mipomersen and proprotein convertase subtilisin kexin-type 9
inhibitors, but these drugs are limited by weak efficacy and not specifically
approved for Lp(a) lowering. Emerging therapies to lower Lp(a) may shed new light
into the potential clinical benefit of lowering Lp(a) in CVD and CAVS.
PMID- 27497507
TI - Cholesterol Guidelines: More Similar Than Different.
AB - A clinician has a large number of guidelines to follow. Searching the words
"cardiovascular" and "guideline" on the website, www.guideline.gov yielded 502
cardiovascular guidelines, 40 alone in 2015. 1 [National Guideline Clearinghouse:
Agency for Healthcare Research and 19 Quality (n.d.)] Similarly, searching the
words "cholesterol" and "guideline" yielded 107 results, 6 alone in 2015. This
information overload can decrease providers' self-efficacy in using guidelines,
particularly if they have inconsistent messages. Moreover, a busy provider can
easily be lost if the emphasis is on highlighting differences rather than
similarities on the same topic. There are several guidelines for management of
blood cholesterol and lipids. Despite being more similar than different, their
similarities have not received as much attention as the differences between them.
Unfortunately, there are still major gaps in current clinical practice even
across these common themes. In this review, we will provide a brief overview of
various cholesterol/lipid guidelines followed by a discussion of the differences
but more importantly, similarities between them.
PMID- 27497508
TI - Preliminary Experience with Transdermal Oxybutynin Patches for Hyperhidrosis.
AB - BACKGROUND AND OBJECTIVE: Hyperhidrosis is very common and has a considerable
impact on patients' quality of life. While oral oxybutynin is associated with
good response rates, adverse effects are common and frequently cause patients to
stop treatment. Following the recent launch of oxybutynin in a transdermal patch
formulation in Spain, we undertook a preliminary study to assess treatment
response and adverse effects in patients with hyperhidrosis. MATERIAL AND
METHODS: This prospective study of 25 patients treated twice weekly with
transdermal oxybutynin patches over 10 weeks assessed treatment response on 2
subjective scales: the Hyperhidrosis Disease Severity Scale (HDSS) and a visual
analog scale (VAS) for sweating. RESULTS: Sixty percent of patients showed an
improvement in HDSS scores. VAS scores improved in all cases, and 68% of patients
achieved a reduction of 3 points or more. Just 2 patients (8%) experienced
treatment-related adverse effects (irritant dermatitis at the patch application
site in both cases). CONCLUSIONS: Although our results are based on a small
sample, they suggest that transdermal oxybutynin could be a useful option for the
treatment of hyperhidrosis and that it has an excellent safety and tolerability
profile.
PMID- 27497509
TI - Kidney Disease and Psoriasis. A New Comorbidity?
AB - Psoriasis is a chronic inflammatory disease that has been associated with
cardiovascular and metabolic comorbidities, particularly in young patients and
patients with more severe forms of the disease. Recent studies have also linked
psoriasis to kidney disease, and this would seem only logical, as the kidney is
both a target of classic cardiovascular risk factors and susceptible to the toxic
effects of some of the traditional drugs used to control psoriasis. In this
article, we would like to draw readers' attention to this recently described
comorbidity and stress the importance of early detection, as once chronic kidney
disease develops, it cannot be reversed. When evaluating patients with psoriasis,
particularly when they are candidates for systemic therapy, we believe it is
important to order laboratory tests including glomerular filtration rate and a
simple urine test to screen for albuminuria (albumin/creatinine ratio).
PMID- 27497510
TI - Complement C3a Mobilizes Dental Pulp Stem Cells and Specifically Guides Pulp
Fibroblast Recruitment.
AB - INTRODUCTION: Complement activation is considered a major mechanism in innate
immunity. Although it is mainly involved in initiating inflammation, recent data
reported its involvement in other processes such as tissue regeneration. In the
dental pulp, complement C5a fragment has been shown to be involved in the
recruitment of dental pulp stem cells (DPSCs). This study sought to investigate
the possible role of C3a, another complement fragment, in the early steps of
dentin-pulp regeneration. METHODS: Expression of C3a receptor (C3aR) was
investigated by immunofluorescence and reverse transcriptase polymerase chain
reaction on cultured pulp fibroblasts, STRO-1-sorted DPSCs, as well as on human
tooth sections in vivo. The effect of C3a on proliferation of both DPSCs and pulp
fibroblasts was investigated by MTT assay. Cell migration under a C3a gradient
was investigated by using microfluidic chemotaxis chambers. RESULTS: C3aR was
expressed in vivo as well as in cultured pulp fibroblasts co-expressing
fibroblast surface protein and in DPSCs co-expressing STRO-1. Addition of
recombinant C3a induced a significant proliferation of both cell types. When
subjected to a C3a gradient, DPSCs were mobilized but not specifically recruited,
whereas pulp fibroblasts were specifically recruited following a C3a gradient.
CONCLUSIONS: These results provide the first demonstration of C3aR expression in
the dental pulp and demonstrate that C3a is involved in increasing DPSCs and
fibroblast proliferation, in mobilizing DPSCs, and in specifically guiding
fibroblast recruitment. This provides an additional link to the tight correlation
between inflammation and tissue regeneration.
PMID- 27497511
TI - 1-year In Vitro Evaluation of Tooth Discoloration Induced by 2 Calcium Silicate
based Cements.
AB - INTRODUCTION: The purpose of this study was to compare tooth discoloration that
occurs in teeth filled with ProRoot MTA (DENTSPLY Tulsa Dental Specialties,
Tulsa, OK) or Biodentine (Septodont, Saint Maur des Fosses, France) over the
course of 1 year. METHODS: Twenty-eight intact premolars were resected 2 mm
apical to the cementoenamel junction and the pulp tissues extirpated via the
cervical cut. After the preparation of occlusal access to the pulp chamber,
specimens were assigned into 4 groups according to a stratified randomization
sampling process: group 1, negative control (dry sterile cotton pellet); group 2,
positive control (blood-moistened cotton pellet); group 3, ProRoot WMTA (DENTSPLY
Tulsa Dental Specialties); and group 4, Biodentine. The experimental materials
were condensed into the crowns and the access sealed with glass ionomer
restorative cement. Color was assessed at baseline (before placement of the
materials), immediately after material filling, after 6 weeks of storage, and
after 1 year using the Commission International de I'Eclairage L*a*b* system.
Change in color, DeltaE, was compared among groups and over time using analysis
of variance. RESULTS: The 4 groups showed a significant decrease in L* values
over time. Differences between Biodentine and WMTA were detected after 1 year,
with the greater variation associated with WMTA (P = .001). The 4 groups
presented a significant increase in DeltaE from baseline to 1 year. All groups
revealed perceptible color changes (DeltaE > 2.3) between immediately after
material filling and after 6 weeks and after 6 weeks and 1 year. After 1 year, no
differences could be detected between Biodentine and WMTA. CONCLUSIONS: Delayed
tooth discoloration was detected for the 2 materials at the 1-year evaluation,
but it was more evident for ProRoot MTA than Biodentine. Luminance was the most
affected parameter, with a higher decrease for ProRoot MTA.
PMID- 27497513
TI - Molecular imaging of the tumor microenvironment.
AB - The tumor microenvironment plays a critical role in tumor initiation,
progression, metastasis, and resistance to therapy. It is different from normal
tissue in the extracellular matrix, vascular and lymphatic networks, as well as
physiologic conditions. Molecular imaging of the tumor microenvironment provides
a better understanding of its function in cancer biology, and thus allowing for
the design of new diagnostics and therapeutics for early cancer diagnosis and
treatment. The clinical translation of cancer molecular imaging is often hampered
by the high cost of commercialization of targeted imaging agents as well as the
limited clinical applications and small market size of some of the agents.
Because many different cancer types share similar tumor microenvironment
features, the ability to target these biomarkers has the potential to provide
clinically translatable molecular imaging technologies for a spectrum of cancers
and broad clinical applications. There has been significant progress in targeting
the tumor microenvironment for cancer molecular imaging. In this review, we
summarize the principles and strategies of recent advances made in molecular
imaging of the tumor microenvironment, using various imaging modalities for early
detection and diagnosis of cancer.
PMID- 27497512
TI - Lipases from the genus Rhizopus: Characteristics, expression, protein engineering
and application.
AB - Lipases are versatile catalysts that hydrolyze ester bonds of water-insoluble
glycerides or carry out reversible reactions at the water/lipid interface. The
remarkable characteristics of lipases from the genus Rhizopus are their high sn
1,3-positional specificity, enantioselectivity and activity in nonaqueous media,
which make them one of the most desirable enzymes for many applications,
including lipid modification and biodiesel and chiral organic compound synthesis.
sn-1,3-Position-specific Rhizopus lipases are particularly useful for the
production of structured triacylglycerols. Significant progress has been made
regarding lipases from the genus Rhizopus, including gene sequencing, elucidation
of the protein structure and catalytic function, heterologous expression and
redesigning Rhizopus lipases for valuable properties, which is receiving
increasing academic and industrial attention. In this review, we present a
comprehensive overview of Rhizopus lipases, focusing on (a) the characteristics
of Rhizopus lipases, (b) Rhizopus lipase genes and structural features, (c)
strategies for heterologous expression of Rhizopus lipase genes in yeast system,
(d) progress in protein engineering for the improvement of the properties of
Rhizopus lipases, and (e) development of biotechnological applications.
PMID- 27497514
TI - A Mobile Phone HIV Medication Adherence Intervention: Acceptability and
Feasibility Study.
AB - We present the findings of a qualitative pilot study designed to describe the
experience of HIV medication adherence using a mobile phone application. Nine
semi-structured focus group discussions were conducted over a 3-month period at
an AIDS Services Organization in Central Texas. The data were analyzed following
the principles of thematic analysis. During analysis, four themes were
identified, and relations between these themes were delineated to reflect the
experiences of the 23 participants. The mobile phone application, Care4TodayTM
Mobile Health Manager, was the intervention tool. Collection of focus group
discussion outcomes over a 3-month period with baseline versus end-of-study data
determined the feasibility and acceptability of this medication adherence
intervention. The findings suggest that when individuals are offered the
necessary resources, such as a mobile phone medication reminder application, they
may have greater success in performing the behavior.
PMID- 27497515
TI - Resuscitation following opioid overdose: Old ideas and new threats.
PMID- 27497516
TI - Higher concentrations of branched-chain amino acids in breast milk of obese
mothers.
AB - OBJECTIVE: Nutrition during fetal life and early childhood is thought to play a
crucial role in the risk for developing metabolic syndrome and cardiovascular
diseases in the future adult and branched-chain amino acids (BCAA) intake may
play a role in the development of obesity. The aim of this study was to compare
the breast milk amino acid profiles of obese and normal weight (control) breast
feeding mothers. METHODS: Fifty obese and 50 control breast-feeding mothers were
enrolled. Age and parity were similar in both groups. Breast milk samples were
collected at the end of the first month of lactation. Free amino acid (FAA)
concentrations in breast milk were determined by ultra-performance liquid
chromatography tandem mass spectrometry. Comparisons between groups were
performed using a two-tailed paired t test. RESULTS: We analyzed 45 breast milk
samples from each group. Body mass index was 34.3 +/- 3.9 kg/m(2) in the obese
group and 21.6 +/- 1.4 kg/m(2) in the control group (P < 10(-4)). BCAA
concentrations were higher in breast milk of obese mothers (95.5 +/- 38.2 MUM
versus 79.8 +/- 30.9 MUM; P = 0.037), as was tyrosine concentration (13.8 +/- 7.1
MUM versus 10.6 +/- 5.2 MUM; P = 0.016). CONCLUSION: The mature breast milk of
obese mothers contained 20% more BCAA and 30% more tyrosine than breast milk of
control mothers. Whether altered breast milk FAA profile affects metabolic risk
in the breast-fed child remains to be explored.
PMID- 27497517
TI - Dietary guanidinoacetic acid increases brain creatine levels in healthy men.
AB - OBJECTIVE: Guanidinoacetic acid (GAA) is an experimental dietary additive that
might act as a creatine source in tissues with high-energy requirements. In this
case study, we evaluated brain levels of creatine in white matter, gray matter,
cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men
and monitored the prevalence and severity of side effects of the intervention.
METHODS: Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA
for the first 4 wk of the intervention; afterward GAA dosage was titrated <=60
mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain
magnetic resonance spectroscopy, clinical chemistry studies, and open-ended
questionnaire for side-effect prevalence and severity. RESULTS: Brain creatine
levels increased in similar fashion in cerebellum, and white and gray matter
after GAA supplementation, with an initial increase of 10.7% reported after 4 wk,
and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P < 0.05).
Thalamus creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased
nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N
acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P < 0.05).
No participants reported any neurologic adverse event (e.g., seizures, tingling,
convulsions) during the intervention. CONCLUSIONS: Supplemental GAA led to a
region-dependent increase of the creatine pool in the human brain. This might be
relevant for restoring cellular bioenergetics in disorders characterized by low
brain creatine and functional enzymatic machinery for creatine synthesis,
including neurodegenerative diseases, brain tumors, or cerebrovascular disease.
PMID- 27497518
TI - Mortality prediction of a body shape index versus traditional anthropometric
measures in an Iranian population: Tehran Lipid and Glucose Study.
AB - OBJECTIVES: A body shape index (ABSI) based on waist circumference (WC) adjusted
for height and weight has been shown to be a risk factor for premature mortality.
The aim of this study was to demonstrate that ABSI predicts mortality hazard
better than other anthropometric measures in an Iranian population. METHODS: The
study population included 9242 Iranian participants in Tehran, aged >=30 y,
followed for a median 10 y. The risk for mortality was estimated by incorporating
ABSI, body mass index (BMI), WC, waist-to-hip ratio (WHpR), and waist-to-height
ratio (WHtR), one at a time, into multivariate models as well as in terms of the
effect size, calibration, discrimination, and added predictive ability. RESULTS:
We documented 487 deaths with the annual incidence rate of mortality per 1000
persons being 3.9 for women and 8.2 for men. ABSI was associated with all-cause
mortality in a curvilinear fashion. ABSI was more strongly associated with all
cause mortality than were BMI, WC, and WHtR. Among women, however, WHpR was
observed to be a stronger predictor of all-cause mortality than ABSI. Among both
men and women, ABSI improved the risk classification based on other
anthropometric measures, the only exception being WHpR. None of the
anthropometric measures studied could add any value to the predictive ability of
the Framingham's general cardiovascular disease algorithm. CONCLUSION: ABSI was
the strongest predictor of all-cause mortality among the anthropometric
measurements, except WHpR in women. When ABSI was added to the Framingham general
cardiovascular disease algorithm, it failed to improve the predictive ability.
PMID- 27497520
TI - Is it time for a HIPAA for physicians?
AB - Practices, hospitals, and healthcare systems are increasingly able to collect
data about individual physician clinical performance. There is a strong
temptation to use the data to make decisions about physicians' quality of care
without first taking the time to establish a system that ensures valid
conclusions. In addition, physicians are not informed that their data are being
used, and thus do not have an opportunity to correct any inaccuracies. A HIPAA
equivalent law or regulation for physicians would help patients and physicians
more accurately address these and other issues related to complex healthcare
data. FERPA provides a useful framework for these concerns.
PMID- 27497519
TI - Fatty acid status and antioxidant defense system in mothers and their newborns
after salmon intake during late pregnancy.
AB - OBJECTIVE: The aim of the present study was to assess the maternal and newborn
status of erythrocyte fatty acids and the antioxidant defense system after the
intake of two portions of salmon per week during late pregnancy. METHODS:
Pregnant women (N = 123) were randomly assigned to continue their habitual diet,
which was low in oily fish (control group, n = 61) or to consume two 150-g salmon
portions per week (salmon group, n = 62) beginning at 20 wk of gestation and
lasting until delivery. Fatty acids, selenium, and glutathione concentrations and
antioxidant defense enzyme activities were measured in maternal erythrocytes at
20, 34, and 38 wk of pregnancy, and in cord erythrocytes collected at birth.
Plasma concentrations of antioxidant molecules were measured. RESULTS: Compared
with the control group, consuming salmon had little effect on erythrocyte fatty
acids in either mothers or newborns. Components of the antioxidant defense system
did not differ between groups. Glutathione peroxidase activity and the
concentrations of tocopherols, retinol, and coenzyme Q10 were significantly lower
in cord blood compared with maternal blood at week 38 in both groups. CONCLUSION:
Maternal and newborn erythrocyte fatty acids are not strongly affected by the
intake of two portions of salmon per week during the second half of pregnancy,
although erythrocyte docosahexaenoic acid might be increased in newborns.
Maternal and newborn antioxidant defense systems are not impaired by intake of
salmon from 20 wk gestation.
PMID- 27497521
TI - Radiologist-Centered Decision Support Applications.
PMID- 27497522
TI - The 2016 ACR Commission on Human Resources Workforce Survey.
AB - PURPOSE: The ACR Commission on Human Resources conducts an annual electronic
survey to better understand the present workforce scenario for radiologists.
METHODS: The Practice of Radiology Environment Database was used to identify
group leads, who were asked to complete an electronic survey developed by the
Commission on Human Resources. The survey asked group leads to report the number
of radiologists they currently employ or supervise, the number hired in 2015, and
the numbers they plan to hire in 2016 and 2019. Leaders were asked to report the
subspecialty area used as the main reason for hiring each physician, as well the
ages and genders of their current workforce. RESULTS: Thirty-two percent of group
leaders, corresponding to 13,074 radiologists or 39% of all practicing
radiologists, responded to this survey. The percentage of practicing radiologists
who are male is 78.6%, compared with 21.4% who are female. Six percent of
radiologists are older than 65 years, and 22% are between the ages of 56 and 65
years. Nineteen percent of radiologists older than 65 years retired in 2015.
Fifteen percent of all radiologists work part-time. Among the part-time
radiologists, 9% are male and 30% are female. General radiologists now make up
only 13.3% of the radiologist workforce. In 2015, 45% of new hires moved from
existing jobs; 55% were first-time hires. In 2016, it is projected that between
1,713 and 2,223 new jobs will be available, a 16.2% increase from hiring in 2015.
CONCLUSIONS: Job opportunities for radiologists have continued to increase since
2013.
PMID- 27497523
TI - The renin angiotensin system, oxidative stress and mitochondrial function in
obesity and insulin resistance.
AB - Obesity is a complex disease characterized by excessive expansion of adipose
tissue and is an important risk factor for chronic diseases such as
cardiovascular disorders, hypertension and type 2 diabetes. Moreover, obesity is
a major contributor to inflammation and oxidative stress, all of which are key
underlying causes for diabetes and insulin resistance. Specifically, adipose
tissue secretes bioactives molecules such as inflammatory hormone angiotensin II,
generated in the Renin Angiotensin System (RAS) from its precursor
angiotensinogen. Accumulated evidence suggests that RAS may serve as a strong
link between obesity and insulin resistance. Dysregulation of RAS also occurs in
several other tissues including those involved in regulation of glucose and whole
body homeostasis as well as insulin sensitivity such as muscle, liver and
pancreas and heart. Here we review the scientific evidence for these interactions
and potential roles for oxidative stress, inflammation and mitochondrial
dysfunction in these target tissues which may mediate effects of RAS in metabolic
diseases. This article is part of a Special Issue entitled: Oxidative Stress and
Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of
Diseases - edited by P. Hemachandra Reddy.
PMID- 27497524
TI - The Role of the Kidney in Disorders of Volume: Core Curriculum 2016.
PMID- 27497525
TI - von Willebrand Factor, ADAMTS13 Activity, and Decline in Kidney Function: A
Population-Based Cohort Study.
AB - BACKGROUND: Altered levels of von Willebrand factor (vWF) and ADAMTS13 can
promote thrombosis and disturb blood flow in kidney microcirculations. We
investigated the association of serum vWF:ADAMTS13 ratio in relation to decline
in kidney function. STUDY DESIGN: Prospective cohort study. SETTING &
PARTICIPANTS: 2,479 individuals (mean age, 65.1+/-5.9 [SD] years; 43% men) from
the population-based Rotterdam Study. PREDICTORS: vWF, ADAMTS13, and vWF:ADAMTS13
ratio. OUTCOMES & MEASUREMENTS: Annual decline in estimated glomerular filtration
rate (eGFR), halving of eGFR, and new-onset eGFR<60mL/min/1.73m2 were assessed.
RESULTS: During a median follow-up of 11 (range, 7.81-13.57) years, 500 cases of
new-onset eGFR<60mL/min/1.73m2 occurred. The population had a mean eGFR decline
of 0.96+/-0.92mL/min/1.73m2 per year. Higher vWF:ADAMTS13 ratio was associated
with steeper annual decline in eGFR (difference, -0.06 [95% CI, -0.09 to -0.02]
mL/min/1.73m2 per year) and higher risk for new-onset eGFR<60mL/min/1.73m2 (OR,
1.13; 95% CI, 1.01-1.27). Likewise, higher vWF:ADAMTS13 ratio was associated with
higher risk for halving of eGFR (OR, 1.40; 95% CI, 1.02-1.93). After adjustment
for cardiovascular risk factors and blood group, effect estimates remained the
same. LIMITATIONS: No data available for albuminuria. Participants were
classified based on a single measurement of vWF and ADAMTS13. CONCLUSIONS: In
this population-based study, we showed that higher vWF:ADAMTS13 ratio is
associated with decline in kidney function, suggesting a role of elevated
prothrombotic factors in the development and progression of kidney disease.
PMID- 27497526
TI - Update on Nephrolithiasis: Core Curriculum 2016.
PMID- 27497528
TI - Combined treatment with chondroitinase ABC and treadmill rehabilitation for
chronic severe spinal cord injury in adult rats.
AB - There are more than 50 times the number of chronic-phase spinal cord injury (SCI)
patients than there are acute patients, and over half of all SCI patients are
severely disabled. However, research focusing on chronic severe contusional SCI
remains very rare. Here, we evaluated whether chondroitinase ABC (C-ABC), a
degradative enzyme directed against chondroitin sulfate proteoglycans (CSPGs),
and treadmill rehabilitation could exert synergistic therapeutic actions against
chronic severe contusional SCI. First, we induced severe contusional SCI in adult
rats, and administered C-ABC intrathecally at 6 weeks post-injury for a period of
one week. Next, we performed treadmill rehabilitation from weeks 6 to 14 after
SCI, for a total period of eight weeks. The initiation of treadmill
rehabilitation triggered slight recovery between weeks 6 and 9, whereas C-ABC
administration stimulated a third phase of recovery between weeks 12 and 14.
Histologically, the C-ABC-treated rats showed an increase in the transverse
residual tissue area and the extent of neuronal fiber regeneration at a site
caudal to the lesion epicenter, and regrowth of putatively regenerating
serotonergic fibers was significantly increased at the epicenter. We suggest
that, when combined with intensive rehabilitation, C-ABC may play a beneficial
role, even in severe and chronic SCI.
PMID- 27497529
TI - Leoligin, the major lignan from Edelweiss, inhibits 3-hydroxy-3-methyl-glutaryl
CoA reductase and reduces cholesterol levels in ApoE-/- mice.
AB - The health benefit through the control of lipid levels in hyperlipidaemic
individuals is evident from a large number of studies. The pharmacological
options to achieve this goal shall be as specific and personalized as the reasons
for and co-factors of hyperlipidaemia. It was the goal of this study to reveal
the impact of leoligin on cholesterol levels and to define its mechanism of
action. Oral application of leoligin in ApoE-/- mice led to significantly reduced
total serum cholesterol levels and a reduction in postprandial blood glucose peak
levels. In the absence of biochemical signs of toxicity, leoligin treatment
resulted in reduced weight gain in mice. The effects of leoligin on serum
cholesterol levels may be due to a direct inhibition of 3-hydroxy-3-methyl
glutaryl-CoA reductase (HMGCR) by a unique, non-statin-like binding mode.
Postprandial serum glucose peaks may be reduced by a mild peroxisome proliferator
activated receptor-gamma (PPAR-gamma) agonistic activity of leoligin. No effect
on atherosclerotic plaque size was observed. As a non-toxic, cholesterol-, peak
glucose-, and weight gain-lowering compound, leoligin continues to fulfil
characteristics of a potential agent for the treatment of cardiovascular disease
(CVD). The counterregulatory overexpression of hepatic HMGCR in leoligin treated
animals possibly explains the missing permanent anti-atherosclerotic effect.
PMID- 27497530
TI - Nanosilver conductive ink: A case study for evaluating the potential risk of
nanotechnology under hypothetical use scenarios.
AB - Engineered nanomaterials (ENMs) are being incorporated into a variety of consumer
products due to unique properties that offer a variety of advantages over bulk
materials. Understanding of the nano-specific risk associated with nano-enabled
technologies, however, continues to lag behind research and development,
registration with regulators, and commercialization. One example of a nano
enabled technology is nanosilver ink, which can be used in commercial ink-jet
printers for the development of low-cost printable electronics. This
investigation utilizes a tiered EHS framework to evaluate the potential nano
specific release, exposure and hazard associated with typical use of both
nanosilver ink and printed circuits. The framework guides determination of the
potential for ENM release from both forms of the technology in simulated use
scenarios, including spilling of the ink, aqueous release (washing) from the
circuits and UV light exposure. The as-supplied ink merits nano-specific
consideration based on the presence of nanoparticles and their persistence in
environmentally-relevant media. The material released from the printed circuits
upon aqueous exposure was characterized by a number of analysis techniques,
including ultracentrifugation and single particle ICP-MS, and the results suggest
that a vast majority of the material was ionic in nature and nano-specific
regulatory scrutiny may be less relevant.
PMID- 27497527
TI - Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized
Outcomes in Nephrology-Hemodialysis (SONG-HD) Consensus Workshop.
AB - Evidence-informed decision making in clinical care and policy in nephrology is
undermined by trials that selectively report a large number of heterogeneous
outcomes, many of which are not patient centered. The Standardized Outcomes in
Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus
workshop on November 7, 2015, to discuss the identification and implementation of
a potential core outcome set for all trials in hemodialysis. The purpose of this
article is to report qualitative analyses of the workshop discussions, describing
the key aspects to consider when establishing core outcomes in trials involving
patients on hemodialysis therapy. Key stakeholders including 8
patients/caregivers and 47 health professionals (nephrologists, policymakers,
industry, and researchers) attended the workshop. Attendees suggested that
identifying core outcomes required equitable stakeholder engagement to ensure
relevance across patient populations, flexibility to consider evolving priorities
over time, deconstruction of language and meaning for conceptual consistency and
clarity, understanding of potential overlap and associations between outcomes,
and an assessment of applicability to the range of interventions in hemodialysis.
For implementation, they proposed that core outcomes must have simple,
inexpensive, and validated outcome measures that could be used in clinical care
(quality indicators) and trials (including pragmatic trials) and endorsement by
regulatory agencies. Integrating these recommendations may foster acceptance and
optimize the uptake and translation of core outcomes in hemodialysis, leading to
more informative research, for better treatment and improved patient outcomes.
PMID- 27497532
TI - Communication: Physical origins of ionization potential shifts in mixed
carboxylic acids and water complexes.
AB - The ionization potential (IP) of the aromatic alpha hydroxy carboxylic acid, 9
hydroxy-9-fluorene carboxylic acid (9HFCA), is shifted by complexation with
hydrogen bonding ligands such as water and formic acid. Generalized Kohn-Sham
energy decomposition analysis decomposes the intermolecular binding energies into
a frozen energy term, polarization, correlation, and/or dispersion energy terms,
as well as terms of geometric relaxation and zero point energy. We observe that
in each dimer the attractive polarization always increases upon ionization,
enhancing binding in the cation and shifting the IP toward the red. For 9HFCA
H2O, a substantial decrease of the repulsive frozen energy in cation further
shifts the IP toward red. For 9HFCA-HCOOH, the increase of the frozen energy
actually occurs in the cation and shifts the IP toward blue. Consistent with the
experimental measurements, our analysis provides new, non-intuitive perspectives
on multiple hydrogen bonds interactions in carboxylic acids and water complexes.
PMID- 27497531
TI - Identifying Inherited and Acquired Genetic Factors Involved in Poor Stem Cell
Mobilization and Donor-Derived Malignancy.
AB - Analysis of the clinical characteristics of hematopoietic stem cell transplant
(HSCT) donors has proven beneficial for identifying cases of heritable
hematopoietic disorders. This study examines poor peripheral blood hematopoietic
stem cell mobilization after granulocyte colony-stimulating factor administration
among 328 donors as a potential marker for suspected familial predisposition to
myeloid malignancies. Here, we present data comparing the clinical
characteristics of poor-mobilizing versus nonpoor-mobilizing donors and the
results of panel-based sequencing of hematopoietic genes in poor-mobilizing
donors. From this analysis, we identified a novel case of a donor-derived
myelodysplastic syndrome in an HSCT recipient that is consistent with clonal
evolution of TET2-mutated clonal hematopoiesis of indeterminate potential (CHIP)
within the donor. This study demonstrates the potential risk of using
hematopoietic stem cells from a donor with CHIP and raises the question of
whether there should be increased screening measures to identify such donors.
PMID- 27497533
TI - Accelerated path integral methods for atomistic simulations at ultra-low
temperatures.
AB - Path integral methods provide a rigorous and systematically convergent framework
to include the quantum mechanical nature of atomic nuclei in the evaluation of
the equilibrium properties of molecules, liquids, or solids at finite
temperature. Such nuclear quantum effects are often significant for light nuclei
already at room temperature, but become crucial at cryogenic temperatures such as
those provided by superfluid helium as a solvent. Unfortunately, the cost of
converged path integral simulations increases significantly upon lowering the
temperature so that the computational burden of simulating matter at the typical
superfluid helium temperatures becomes prohibitive. Here we investigate how
accelerated path integral techniques based on colored noise generalized Langevin
equations, in particular the so-called path integral generalized Langevin
equation thermostat (PIGLET) variant, perform in this extreme quantum regime
using as an example the quasi-rigid methane molecule and its highly fluxional
protonated cousin, CH5 (+). We show that the PIGLET technique gives a speedup of
two orders of magnitude in the evaluation of structural observables and quantum
kinetic energy at ultralow temperatures. Moreover, we computed the spatial spread
of the quantum nuclei in CH4 to illustrate the limits of using such colored noise
thermostats close to the many body quantum ground state.
PMID- 27497534
TI - A many-body states picture of electronic friction: The case of multiple orbitals
and multiple electronic states.
AB - We present a very general form of electronic friction as present when a molecule
with multiple orbitals hybridizes with a metal electrode. To develop this picture
of friction, we embed the quantum-classical Liouville equation (QCLE) within a
classical master equation (CME). Thus, this article extends our previous work
analyzing the case of one electronic level, as we may now treat the case of
multiple levels and many electronic molecular states. We show that, in the
adiabatic limit, where electron transitions are much faster than nuclear motion,
the QCLE-CME reduces to a Fokker-Planck equation, such that nuclei feel an
average force as well as friction and a random force-as caused by their
interaction with the metallic electrons. Finally, we show numerically and
analytically that our frictional results agree with other published results
calculated using non-equilibrium Green's functions. Numerical recipes for solving
this QCLE-CME will be provided in a subsequent paper.
PMID- 27497535
TI - Ultra-fast computation of electronic spectra for large systems by tight-binding
based simplified Tamm-Dancoff approximation (sTDA-xTB).
AB - The computational bottleneck of the extremely fast simplified Tamm-Dancoff
approximated (sTDA) time-dependent density functional theory procedure [S.
Grimme, J. Chem. Phys. 138, 244104 (2013)] for the computation of electronic
spectra for large systems is the determination of the ground state Kohn-Sham
orbitals and eigenvalues. This limits such treatments to single structures with a
few hundred atoms and hence, e.g., sampling along molecular dynamics trajectories
for flexible systems or the calculation of chromophore aggregates is often not
possible. The aim of this work is to solve this problem by a specifically
designed semi-empirical tight binding (TB) procedure similar to the well
established self-consistent-charge density functional TB scheme. The new special
purpose method provides orbitals and orbital energies of hybrid density
functional character for a subsequent and basically unmodified sTDA procedure.
Compared to many previous semi-empirical excited state methods, an advantage of
the ansatz is that a general eigenvalue problem in a non-orthogonal, extended
atomic orbital basis is solved and therefore correct occupied/virtual orbital
energy splittings as well as Rydberg levels are obtained. A key idea for the
success of the new model is that the determination of atomic charges (describing
an effective electron-electron interaction) and the one-particle spectrum is
decoupled and treated by two differently parametrized Hamiltonians/basis sets.
The three-diagonalization-step composite procedure can routinely compute broad
range electronic spectra (0-8 eV) within minutes of computation time for systems
composed of 500-1000 atoms with an accuracy typical of standard time-dependent
density functional theory (0.3-0.5 eV average error). An easily extendable
parametrization based on coupled-cluster and density functional computed
reference data for the elements H-Zn including transition metals is described.
The accuracy of the method termed sTDA-xTB is first benchmarked for vertical
excitation energies of open- and closed-shell systems in comparison to other semi
empirical methods and applied to exemplary problems in electronic spectroscopy.
As side products of the development, a robust and efficient valence electron TB
method for the accurate determination of atomic charges as well as a more
accurate calculation scheme of dipole rotatory strengths within the Tamm-Dancoff
approximation is proposed.
PMID- 27497536
TI - Comparison of fully internally and strongly contracted multireference
configuration interaction procedures.
AB - Multireference (MR) methods occupy an important class of approaches in quantum
chemistry. In many instances, for example, in studying complex magnetic
properties of transition metal complexes, they are actually the only physically
satisfactory choice. In traditional MR approaches, single and double excitations
are performed with respect to all reference configurations (or configuration
state functions, CSFs), which leads to an explosive increase of computational
cost for larger reference spaces. This can be avoided by the internal contraction
scheme proposed by Meyer and Siegbahn, which effectively reduces the number of
wavefunction parameters to their single-reference counterpart. The "fully
internally contracted" scheme (FIC) is well known from the popular CASPT2
approach. An even shorter expansion of the wavefunction is possible with the
"strong contraction" (SC) scheme proposed by Angeli and Malrieu in their NEVPT2
approach. Promising multireference configuration interaction formulations (MRCI)
employing internal contraction and strong contraction have been reported by
several authors. In this work, we report on the implementation of the FIC-MRCI
and SC-MRCI methodologies, using a computer assisted implementation strategy. The
methods are benchmarked against the traditional uncontracted MRCI approach for
ground and excited states of small molecules (N2, O2, CO, CO(+), OH, CH, and CN).
For ground states, the comparison includes the "partially internally contracted"
MRCI based on the Celani-Werner ansatz (PC-MRCI). For the three contraction
schemes, the average errors range from 2% to 6% of the uncontracted MRCI
correlation energies. Excitation energies are reproduced with ~0.2 eV accuracy.
In most cases, the agreement is better than 0.2 eV, even in cases with very large
differential correlation contributions as exemplified for the d-d and ligand-to
metal charge transfer transitions of a Cu[NH3]4 (2+) model complex. The benchmark
is supplemented with the investigation of typical potential energy surfaces
(i.e., N2, HF, LiF, BeH2, ethane C-C bond stretching, and the ethylene double
bond torsion). Our results indicate that the SC-scheme, which is successful in
the context of second- and third-order perturbation theory, does not offer
computational advantages and at the same time leads to much larger errors than
the PC and FIC schemes. We discuss the advantages and disadvantages of the PC and
FIC schemes, which are of comparable accuracy and, for the systems tested, also
of comparable efficiency.
PMID- 27497537
TI - Size consistent formulations of the perturb-then-diagonalize Moller-Plesset
perturbation theory correction to non-orthogonal configuration interaction.
AB - In this paper we introduce two size consistent forms of the non-orthogonal
configuration interaction with second-order Moller-Plesset perturbation theory
method, NOCI-MP2. We show that the original NOCI-MP2 formulation [S. R. Yost, T.
Kowalczyk, and T. VanVoorh, J. Chem. Phys. 193, 174104 (2013)], which is a
perturb-then-diagonalize multi-reference method, is not size consistent. We also
show that this causes significant errors in large systems like the linear acenes.
By contrast, the size consistent versions of the method give satisfactory results
for singlet and triplet excited states when compared to other multi-reference
methods that include dynamic correlation. For NOCI-MP2 however, the number of
required determinants to yield similar levels of accuracy is significantly
smaller. These results show the promise of the NOCI-MP2 method, though work still
needs to be done in creating a more consistent black-box approach to computing
the determinants that comprise the many-electron NOCI basis.
PMID- 27497538
TI - A robust and accurate formulation of molecular and colloidal electrostatics.
AB - This paper presents a re-formulation of the boundary integral method for the
Debye-Huckel model of molecular and colloidal electrostatics that removes the
mathematical singularities that have to date been accepted as an intrinsic part
of the conventional boundary integral equation method. The essence of the present
boundary regularized integral equation formulation consists of subtracting a
known solution from the conventional boundary integral method in such a way as to
cancel out the singularities associated with the Green's function. This approach
better reflects the non-singular physical behavior of the systems on boundaries
with the benefits of the following: (i) the surface integrals can be evaluated
accurately using quadrature without any need to devise special numerical
integration procedures, (ii) being able to use quadratic or spline function
surface elements to represent the surface more accurately and the variation of
the functions within each element is represented to a consistent level of
precision by appropriate interpolation functions, (iii) being able to calculate
electric fields, even at boundaries, accurately and directly from the potential
without having to solve hypersingular integral equations and this imparts high
precision in calculating the Maxwell stress tensor and consequently,
intermolecular or colloidal forces, (iv) a reliable way to handle geometric
configurations in which different parts of the boundary can be very close
together without being affected by numerical instabilities, therefore potentials,
fields, and forces between surfaces can be found accurately at surface
separations down to near contact, and (v) having the simplicity of a formulation
that does not require complex algorithms to handle singularities will result in
significant savings in coding effort and in the reduction of opportunities for
coding errors. These advantages are illustrated using examples drawn from
molecular and colloidal electrostatics.
PMID- 27497539
TI - Development of DPD coarse-grained models: From bulk to interfacial properties.
AB - A new Bayesian method was recently introduced for developing coarse-grain (CG)
force fields for molecular dynamics. The CG models designed for dissipative
particle dynamics (DPD) are optimized based on trajectory matching. Here we
extend this method to improve transferability across thermodynamic conditions. We
demonstrate the capability of the method by developing a CG model of n-pentane
from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG
DPD model to the calculation of the surface tension of the liquid-vapor interface
over a large range of temperatures. The coexisting densities, vapor pressures,
and surface tensions calculated with different CG and atomistic models are
compared to experiments. Depending on the database used for the development of
the potentials, it is possible to build a CG model which performs very well in
the reproduction of the surface tension on the orthobaric curve.
PMID- 27497540
TI - Mixed quantum-classical simulations of the vibrational relaxation of photolyzed
carbon monoxide in a hemoprotein.
AB - We present mixed quantum-classical simulations on relaxation and dephasing of
vibrationally excited carbon monoxide within a protein environment. The
methodology is based on a vibrational surface hopping approach treating the
vibrational states of CO quantum mechanically, while all remaining degrees of
freedom are described by means of classical molecular dynamics. The CO
vibrational states form the "surfaces" for the classical trajectories of protein
and solvent atoms. In return, environmentally induced non-adiabatic couplings
between these states cause transitions describing the vibrational relaxation from
first principles. The molecular dynamics simulation yields a detailed atomistic
picture of the energy relaxation pathways, taking the molecular structure and
dynamics of the protein and its solvent fully into account. Using the ultrafast
photolysis of CO in the hemoprotein FixL as an example, we study the relaxation
of vibrationally excited CO and evaluate the role of each of the FixL residues
forming the heme pocket.
PMID- 27497541
TI - Global and local curvature in density functional theory.
AB - Piecewise linearity of the energy with respect to fractional electron removal or
addition is a requirement of an electronic structure method that necessitates the
presence of a derivative discontinuity at integer electron occupation. Semi-local
exchange-correlation (xc) approximations within density functional theory (DFT)
fail to reproduce this behavior, giving rise to deviations from linearity with a
convex global curvature that is evidence of many-electron, self-interaction error
and electron delocalization. Popular functional tuning strategies focus on
reproducing piecewise linearity, especially to improve predictions of optical
properties. In a divergent approach, Hubbard U-augmented DFT (i.e., DFT+U) treats
self-interaction errors by reducing the local curvature of the energy with
respect to electron removal or addition from one localized subshell to the
surrounding system. Although it has been suggested that DFT+U should
simultaneously alleviate global and local curvature in the atomic limit, no
detailed study on real systems has been carried out to probe the validity of this
statement. In this work, we show when DFT+U should minimize deviations from
linearity and demonstrate that a "+U" correction will never worsen the deviation
from linearity of the underlying xc approximation. However, we explain varying
degrees of efficiency of the approach over 27 octahedral transition metal
complexes with respect to transition metal (Sc-Cu) and ligand strength (CO, NH3,
and H2O) and investigate select pathological cases where the delocalization error
is invisible to DFT+U within an atomic projection framework. Finally, we
demonstrate that the global and local curvatures represent different quantities
that show opposing behavior with increasing ligand field strength, and we
identify where these two may still coincide.
PMID- 27497542
TI - The adiabatic limit of the exact factorization of the electron-nuclear wave
function.
AB - We propose a procedure to analyze the relation between the exact factorization of
the electron-nuclear wave function and the Born-Oppenheimer approximation. We
define the adiabatic limit as the limit of infinite nuclear mass. To this end, we
introduce a unit system that singles out the dependence on the electron-nuclear
mass ratio of each term appearing in the equations of the exact factorization. We
observe how non-adiabatic effects induced by the coupling to the nuclear motion
affect electronic properties and we analyze the leading term, connecting it to
the classical nuclear momentum. Its dependence on the mass ratio is tested
numerically on a model of proton-coupled electron transfer in different non
adiabatic regimes.
PMID- 27497543
TI - Correlation consistent basis sets for lanthanides: The atoms La-Lu.
AB - Using the 3rd-order Douglas-Kroll-Hess (DKH3) Hamiltonian, all-electron
correlation consistent basis sets of double-, triple-, and quadruple-zeta quality
have been developed for the lanthanide elements La through Lu. Basis sets
designed for the recovery of valence correlation (defined here as 4f5s5p5d6s), cc
pVnZ-DK3, and outer-core correlation (valence + 4s4p4d), cc-pwCVnZ-DK3, are
reported (n = D, T, and Q). Systematic convergence of both Hartree-Fock and
correlation energies towards their respective complete basis set (CBS) limits are
observed. Benchmark calculations of the first three ionization potentials (IPs)
of La through Lu are reported at the DKH3 coupled cluster singles and doubles
with perturbative triples, CCSD(T), level of theory, including effects of
correlation down through the 4s electrons. Spin-orbit coupling is treated at the
2-component HF level. After extrapolation to the CBS limit, the average errors
with respect to experiment were just 0.52, 1.14, and 4.24 kcal/mol for the 1st,
2nd, and 3rd IPs, respectively, compared to the average experimental
uncertainties of 0.03, 1.78, and 2.65 kcal/mol, respectively. The new basis sets
are also used in CCSD(T) benchmark calculations of the equilibrium geometries,
atomization energies, and heats of formation for Gd2, GdF, and GdF3. Except for
the equilibrium geometry and harmonic frequency of GdF, which are accurately
known from experiment, all other calculated quantities represent significant
improvements compared to the existing experimental quantities. With estimated
uncertainties of about +/-3 kcal/mol, the 0 K atomization energies (298 K heats
of formation) are calculated to be (all in kcal/mol): 33.2 (160.1) for Gd2, 151.7
(-36.6) for GdF, and 447.1 (-295.2) for GdF3.
PMID- 27497544
TI - Locality of correlation in density functional theory.
AB - The Hohenberg-Kohn density functional was long ago shown to reduce to the Thomas
Fermi (TF) approximation in the non-relativistic semiclassical (or large-Z) limit
for all matter, i.e., the kinetic energy becomes local. Exchange also becomes
local in this limit. Numerical data on the correlation energy of atoms support
the conjecture that this is also true for correlation, but much less relevant to
atoms. We illustrate how expansions around a large particle number are equivalent
to local density approximations and their strong relevance to density functional
approximations. Analyzing highly accurate atomic correlation energies, we show
that EC -> -AC ZlnZ + BCZ as Z -> infinity, where Z is the atomic number, AC is
known, and we estimate BC to be about 37 mhartree. The local density
approximation yields AC exactly, but a very incorrect value for BC, showing that
the local approximation is less relevant for the correlation alone. This limit is
a benchmark for the non-empirical construction of density functional
approximations. We conjecture that, beyond atoms, the leading correction to the
local density approximation in the large-Z limit generally takes this form, but
with BC a functional of the TF density for the system. The implications for the
construction of approximate density functionals are discussed.
PMID- 27497545
TI - How wet should be the reaction coordinate for ligand unbinding?
AB - We use a recently proposed method called Spectral Gap Optimization of Order
Parameters (SGOOP) [P. Tiwary and B. J. Berne, Proc. Natl. Acad. Sci. U. S. A.
113, 2839 (2016)], to determine an optimal 1-dimensional reaction coordinate (RC)
for the unbinding of a bucky-ball from a pocket in explicit water. This RC is
estimated as a linear combination of the multiple available order parameters that
collectively can be used to distinguish the various stable states relevant for
unbinding. We pay special attention to determining and quantifying the degree to
which water molecules should be included in the RC. Using SGOOP with under
sampled biased simulations, we predict that water plays a distinct role in the
reaction coordinate for unbinding in the case when the ligand is sterically
constrained to move along an axis of symmetry. This prediction is validated
through extensive calculations of the unbinding times through metadynamics and by
comparison through detailed balance with unbiased molecular dynamics estimate of
the binding time. However when the steric constraint is removed, we find that the
role of water in the reaction coordinate diminishes. Here instead SGOOP
identifies a good one-dimensional RC involving various motional degrees of
freedom.
PMID- 27497547
TI - LCAO-based theoretical study of PbTiO3 crystal to search for parity and time
reversal violating interaction in solids.
AB - An experiment towards the search for the interaction of the Schiff moment (S) of
the (207)Pb nuclei with electrons in PbTiO3 crystal which violates the time
reversal (T) and space parity (P) symmetries was proposed by Mukhamedjanov and
Sushkov [Phys. Rev. A 72, 034501 (2005)]. The interpretation of the experiment in
terms of the Schiff moment requires knowledge of an electronic density gradient
parameter (usually designated as X) on the Pb nucleus in the crystal, which is
determined by the electronic structure of the crystal. Here we propose a
theoretical approach to calculate the properties in solids which are directly
sensitive to the changes of valence electron densities in atomic cores but not in
the valence spatial regions (Mossbauer parameters, hyperfine structure (HFS)
constants, parameters of T,P-odd Hamiltonians, etc. [L. V. Skripnikov and A. V.
Titov, Phys. Rev. A 91, 042504 (2015)]). It involves constructing the crystalline
orbitals via the linear combination of atomic orbitals and employs a two-step
concept of calculating such properties that was earlier proposed by us for the
case of heavy-atom molecules. The application of the method to the PbTiO3 crystal
results in the energy shift, Deltaepsilon=0.82*10(6)S((207)Pb)eaB (3)eV, due to
the T,P-odd interactions. The value is compared to the corresponding parameter in
diatomic molecules (TlF, RaO, PbO), which have been proposed and used in the past
decades in the search for the nuclear Schiff moment. We also present the
calculation of the electric field gradient at the Pb nucleus in PbTiO3 for the
comparison with other solid-state electronic structure approaches.
PMID- 27497546
TI - Stochastic level-set variational implicit-solvent approach to solute-solvent
interfacial fluctuations.
AB - Recent years have seen the initial success of a variational implicit-solvent
model (VISM), implemented with a robust level-set method, in capturing
efficiently different hydration states and providing quantitatively good
estimation of solvation free energies of biomolecules. The level-set minimization
of the VISM solvation free-energy functional of all possible solute-solvent
interfaces or dielectric boundaries predicts an equilibrium biomolecular
conformation that is often close to an initial guess. In this work, we develop a
theory in the form of Langevin geometrical flow to incorporate solute-solvent
interfacial fluctuations into the VISM. Such fluctuations are crucial to
biomolecular conformational changes and binding process. We also develop a
stochastic level-set method to numerically implement such a theory. We describe
the interfacial fluctuation through the "normal velocity" that is the solute
solvent interfacial force, derive the corresponding stochastic level-set equation
in the sense of Stratonovich so that the surface representation is independent of
the choice of implicit function, and develop numerical techniques for solving
such an equation and processing the numerical data. We apply our computational
method to study the dewetting transition in the system of two hydrophobic plates
and a hydrophobic cavity of a synthetic host molecule cucurbit[7]uril. Numerical
simulations demonstrate that our approach can describe an underlying system
jumping out of a local minimum of the free-energy functional and can capture
dewetting transitions of hydrophobic systems. In the case of two hydrophobic
plates, we find that the wavelength of interfacial fluctuations has a strong
influence to the dewetting transition. In addition, we find that the estimated
energy barrier of the dewetting transition scales quadratically with the inter
plate distance, agreeing well with existing studies of molecular dynamics
simulations. Our work is a first step toward the inclusion of fluctuations into
the VISM and understanding the impact of interfacial fluctuations on biomolecular
solvation with an implicit-solvent approach.
PMID- 27497548
TI - Rovibrational states of Wigner molecules in spherically symmetric confining
potentials.
AB - The strong-localization limit of three-dimensional Wigner molecules, in which
repulsively interacting particles are confined by a weak spherically symmetric
potential, is investigated. An explicit prescription for computation of
rovibrational wavefunctions and energies that are asymptotically exact at this
limit is presented. The prescription is valid for systems with arbitrary
angularly-independent interparticle and confining potentials, including those
involving Coulombic and screened (i.e., Yukawa/Debye) interactions. The necessary
derivations are greatly simplified by explicit constructions of the Eckart frame
and the parity-adapted primitive wavefunctions. The performance of the new
formalism is illustrated with the three- and four-electron harmonium atoms at
their strong-correlation limits. In particular, the involvement of vibrational
modes with the E symmetry is readily pinpointed as the origin of the "anomalous"
weak-confinement behavior of the (1)S+ state of the four-electron species that is
absent in its (1)D+ companion of the strong-confinement regime.
PMID- 27497549
TI - Assessment of multireference approaches to explicitly correlated full
configuration interaction quantum Monte Carlo.
AB - The Full Configuration Interaction Quantum Monte Carlo (FCIQMC) method has proved
able to provide near-exact solutions to the electronic Schrodinger equation
within a finite orbital basis set, without relying on an expansion about a
reference state. However, a drawback to the approach is that being based on an
expansion of Slater determinants, the FCIQMC method suffers from a basis set
incompleteness error that decays very slowly with the size of the employed single
particle basis. The FCIQMC results obtained in a small basis set can be improved
significantly with explicitly correlated techniques. Here, we present a study
that assesses and compares two contrasting "universal" explicitly correlated
approaches that fit into the FCIQMC framework: the [2]R12 method of Kong and
Valeev [J. Chem. Phys. 135, 214105 (2011)] and the explicitly correlated
canonical transcorrelation approach of Yanai and Shiozaki [J. Chem. Phys. 136,
084107 (2012)]. The former is an a posteriori internally contracted perturbative
approach, while the latter transforms the Hamiltonian prior to the FCIQMC
simulation. These comparisons are made across the 55 molecules of the G1 standard
set. We found that both methods consistently reduce the basis set incompleteness,
for accurate atomization energies in small basis sets, reducing the error from 28
mEh to 3-4 mEh. While many of the conclusions hold in general for any combination
of multireference approaches with these methodologies, we also consider FCIQMC
specific advantages of each approach.
PMID- 27497550
TI - Accurate reaction-diffusion operator splitting on tetrahedral meshes for parallel
stochastic molecular simulations.
AB - Spatial stochastic molecular simulations in biology are limited by the intense
computation required to track molecules in space either in a discrete time or
discrete space framework, which has led to the development of parallel methods
that can take advantage of the power of modern supercomputers in recent years. We
systematically test suggested components of stochastic reaction-diffusion
operator splitting in the literature and discuss their effects on accuracy. We
introduce an operator splitting implementation for irregular meshes that enhances
accuracy with minimal performance cost. We test a range of models in small-scale
MPI simulations from simple diffusion models to realistic biological models and
find that multi-dimensional geometry partitioning is an important consideration
for optimum performance. We demonstrate performance gains of 1-3 orders of
magnitude in the parallel implementation, with peak performance strongly
dependent on model specification.
PMID- 27497551
TI - Measuring a hidden coordinate: Rate-exchange kinetics from 3D correlation
functions.
AB - Nonexponential kinetics imply the existence of at least one slow variable other
than the observable, that is, the system has a "hidden" coordinate. We develop a
simple, but general, model that allows multidimensional correlation functions to
be calculated for these systems. Homogeneous and heterogeneous mechanisms are
both included, and slow exchange of the rates is allowed. This model shows that
2D and 3D correlation functions of the observable measure the distribution and
kinetics of the hidden coordinate controlling the rate exchange. Both the mean
exchange time and the shape of the exchange relaxation are measurable. However,
complications arise because higher correlation functions are sums of multiple
"pathways," each of which measures different dynamics. Only one 3D pathway
involves exchange dynamics. Care must be used to extract exchange dynamics
without contamination from other processes.
PMID- 27497552
TI - DMRG-CASPT2 study of the longitudinal static second hyperpolarizability of all
trans polyenes.
AB - We have implemented internally contracted complete active space second order
perturbation theory (CASPT2) with the density matrix renormalization group (DMRG)
as active space solver [Y. Kurashige and T. Yanai, J. Chem. Phys. 135, 094104
(2011)]. Internally contracted CASPT2 requires to contract the generalized Fock
matrix with the 4-particle reduced density matrix (4-RDM) of the reference
wavefunction. The required 4-RDM elements can be obtained from 3-particle reduced
density matrices (3-RDM) of different wavefunctions, formed by symmetry
conserving single-particle excitations op top of the reference wavefunction. In
our spin-adapted DMRG code chemps2 https://github.com/sebwouters/chemps2, we
decompose these excited wavefunctions as spin-adapted matrix product states and
calculate their 3-RDM in order to obtain the required contraction of the
generalized Fock matrix with the 4-RDM of the reference wavefunction. In this
work, we study the longitudinal static second hyperpolarizability of all-trans
polyenes C2nH2n+2 [n = 4-12] in the cc-pVDZ basis set. DMRG-SCF and DMRG-CASPT2
yield substantially lower values and scaling with system size compared to RHF and
MP2, respectively.
PMID- 27497553
TI - Insights into the spurious long-range nature of local r-dependent non-local
exchange-correlation kernels.
AB - A systematic route to go beyond the exact exchange plus random phase
approximation (RPA) is to include a physical exchange-correlation kernel in the
adiabatic-connection fluctuation-dissipation theorem. In the previous study [D.
Lu, J. Chem. Phys. 140, 18A520 (2014)], we found that non-local kernels with a
screening length depending on the local Wigner-Seitz radius, rs(r), suffer an
error associated with a spurious long-range repulsion in van der Waals bounded
systems, which deteriorates the binding energy curve as compared to RPA. We
analyze the source of the error and propose to replace rs(r) by a global, average
rs in the kernel. Exemplary studies with the Corradini, del Sole, Onida, and
Palummo kernel show that while this change does not affect the already
outstanding performance in crystalline solids, using an average rs significantly
reduces the spurious long-range tail in the exchange-correlation kernel in van
der Waals bounded systems. When this method is combined with further corrections
using local dielectric response theory, the binding energy of the Kr dimer is
improved three times as compared to RPA.
PMID- 27497554
TI - Dynamic NMR under nonstationary conditions: Theoretical model, numerical
calculation, and potential of application.
AB - An expression has been derived for the time dependence of the NMR line shape for
systems with multi-site chemical exchange in the absence of spin-spin coupling,
in a zero saturation limit. The dynamics of variation of the NMR line shape with
time is considered in detail for the case of two-site chemical exchange.
Mathematical programs have been designed for numerical simulation of the NMR
spectra of chemical exchange systems. The analytical expressions obtained are
useful for NMR line shape simulations for systems with photoinduced chemical
exchange.
PMID- 27497555
TI - Fragmentation pathways of tungsten hexacarbonyl clusters upon electron
ionization.
AB - Electron ionization of neat tungsten hexacarbonyl (W(CO)6) clusters has been
investigated in a crossed electron-molecular beam experiment coupled with a mass
spectrometer system. The molecule is used for nanofabrication processes through
electron beam induced deposition and ion beam induced deposition techniques.
Positive ion mass spectra of W(CO)6 clusters formed by electron ionization at 70
eV contain the ion series of the type W(CO)n (+) (0 <= n <= 6) and W2(CO)n (+) (0
<= n <= 12). In addition, a series of peaks are observed and have been assigned
to WC(CO)n (+) (0 <= n <= 3) and W2C(CO)n (+) (0 <= n <= 10). A distinct change
of relative fragment ion intensity can be observed for clusters compared to the
single molecule. The characteristic fragmentation pattern obtained in the mass
spectra can be explained by a sequential decay of the ionized organometallic,
which is also supported by the study of the clusters when embedded in helium
nanodroplets. In addition, appearance energies for the dissociative ionization
channels for singly charged ions have been estimated from experimental ion
efficiency curves.
PMID- 27497556
TI - High-resolution photoelectron imaging spectroscopy of cryogenically cooled Fe4O(
) and Fe5O(.).
AB - We report high-resolution photodetachment spectra of the cryogenically cooled
iron monoxide clusters Fe4O(-) and Fe5O(-) obtained with slow photoelectron
velocity-map imaging (cryo-SEVI). Well-resolved vibrational progressions are
observed in both sets of spectra, and transitions to low-lying excited states of
both species are seen. In order to identify the structural isomers, electronic
states, and vibrational modes that contribute to the cryo-SEVI spectra of these
clusters, experimental results are compared with density functional theory
calculations and Franck-Condon simulations. The main bands observed in the SEVI
spectra are assigned to the (15)A2<-(16)B2 photodetachment transition of Fe4O(-)
and the (17)A'<-(18)A" photodetachment transition of Fe5O(-). We report electron
affinities of 1.6980(3) eV for Fe4O and 1.8616(3) eV for Fe5O, although there is
some uncertainty as to whether the (15)A2 state is the true ground state of Fe4O.
The iron atoms have a distorted tetrahedral geometry in Fe4O(0/-) and a distorted
trigonal-bipyramidal arrangement in Fe5O(0/-). For both neutral and anionic
species, the oxygen atom preferably binds in a MU2-oxo configuration along the
cluster edge. This finding is in contrast to prior predictions that Fe5O(0/-)
exhibits a MU3 face-bound structure.
PMID- 27497557
TI - Dynamical tunneling versus fast diffusion for a non-convex Hamiltonian.
AB - This paper attempts to resolve the issue of the nature of the 0.01-0.1 cm(-1)
peak splittings observed in high-resolution IR spectra of polyatomic molecules.
One hypothesis is that these splittings are caused by dynamical tunneling, a
quantum-mechanical phenomenon whereby energy flows between two disconnected
regions of phase-space across dynamical barriers. However, a competing classical
mechanism for energy flow is Arnol'd diffusion, which connects different regions
of phase-space by a resonance network known as the Arnol'd web. The speed of
diffusion is bounded by the Nekhoroshev theorem, which guarantees stability on
exponentially long time scales if the Hamiltonian is steep. Here we consider a
non-convex Hamiltonian that contains the characteristics of a molecular
Hamiltonian, but does not satisfy the Nekhoroshev theorem. The diffusion along
the Arnol'd web is expected to be fast for a non-convex Hamiltonian. While fast
diffusion is an unlikely competitor for longtime energy flow in molecules, we
show how dynamical tunneling dominates compared to fast diffusion in the nearly
integrable regime for a non-convex Hamiltonian, as well as present a new kind of
dynamical tunneling.
PMID- 27497558
TI - The polar 2e/12c bond in phenalenyl-azaphenalenyl hetero-dimers: Stronger
stacking interaction and fascinating interlayer charge transfer.
AB - An increasing number of chemists have focused on the two-electron/multicenter
bond (2e/mc) that was first introduced to interpret the bonding mechanism of
radical dimers. Herein, we report the polar two-electron/twelve center (2e/12c)
bonding character in a series of phenalenyl-azaphenalenyl radical hetero-dimers.
Interestingly, the bonding energy of weaker polar hetero-dimer (P-TAP) is
dominated by the overlap of the two different singly occupied molecular orbital
of radicals, while that of stronger polar hetero-dimer (P-HAP) is dominated by
the electrostatic attraction. Results show that the difference between the
electronegativity of the monomers plays a prominent role in the essential
attribution of the polar 2e/12c bond. Correspondingly, a stronger stacking
interaction in the hetero-dimer could be effectively achieved by increasing the
difference of nitrogen atoms number between the monomers. It is worthy of note
that an interesting interlayer charge transfer character is induced in the polar
hetero-dimers, which is dependent on the difference between the electronegativity
of the monomers. It is our expectation that the new knowledge about the bonding
nature of radical hetero-dimers might provide important information for designing
radical based functional materials with various applications.
PMID- 27497559
TI - Aging kinetics of levoglucosan orientational glass as a rate dispersion process
and consequences for the heterogeneous dynamics view.
AB - Aging kinetics of a glass is currently modeled in terms of slowing of its alpha
relaxation dynamics, whose features are interpreted in terms of dynamic
heterogeneity, i.e., formation and decay of spatially and temporally distinct nm
size regions. To test the merits of this view, we studied the calorimetric
effects of aging an orientational glass of levoglucosan crystal in which such
regions would not form in the same way as they form in liquids, and persist in
structural glasses, because there is no liquid-like molecular diffusion in the
crystal. By measuring the heat capacity, Cp, we determined the change in the
enthalpy, H, and the entropy, S, during two aging-protocols: (a) keeping the
samples isothermally at temperature, Ta, and measuring the changes after
different aging times, ta, and (b) keeping the samples at different Tas and
measuring the changes after the same ta. A model-free analysis of the data shows
that as ta is increased (procedure (a)), H and S decrease according to a
dispersive rate kinetics, and as Ta is increased (procedure (b)), H and S first
increase, reach a local maximum at a certain Ta, and then decrease. Even though
there is no translational diffusion to produce (liquid-like) free volume, and no
translational-rotational decoupling, the aging features are indistinguishable
from those of structural glasses. We also find that the Kohlrausch parameter,
originally fitted to the glass-aging data, decreases with decrease in Ta, which
is incompatible with the current use of the aging data for estimating the alpha
relaxation time. We argue that the vibrational state of a glass is naturally
incompatible with its configurational state, and both change on aging until they
are compatible, in the equilibrium liquid. So, dipolar fluctuations seen as the
alpha-relaxation would not be the same motions that cause aging. We suggest that
aging kinetics is intrinsically dispersive with its own characteristic rate
constant and it does not yield the alpha-relaxation rate. In this view,
thermodynamic and other properties define the fictive temperature; the real or
imaginary components of a dynamic property do not define it. While particles'
overall motions may still play a crucial role in (structural) glass physics, we
conclude that translational diffusion alone is not a requirement for structure
stabilization on aging of a kinetically frozen state.
PMID- 27497560
TI - Dynamic measurements and simulations of airborne picolitre-droplet coalescence in
holographic optical tweezers.
AB - We report studies of the coalescence of pairs of picolitre aerosol droplets
manipulated with holographic optical tweezers, probing the shape relaxation
dynamics following coalescence by simultaneously monitoring the intensity of
elastic backscattered light (EBL) from the trapping laser beam (time resolution
on the order of 100 ns) while recording high frame rate camera images (time
resolution <10 MUs). The goals of this work are to: resolve the dynamics of
droplet coalescence in holographic optical traps; assign the origin of key
features in the time-dependent EBL intensity; and validate the use of the EBL
alone to precisely determine droplet surface tension and viscosity. For low
viscosity droplets, two sequential processes are evident: binary coalescence
first results from the overlap of the optical traps on the time scale of
microseconds followed by the recapture of the composite droplet in an optical
trap on the time scale of milliseconds. As droplet viscosity increases, the
relaxation in droplet shape eventually occurs on the same time scale as
recapture, resulting in a convoluted evolution of the EBL intensity that inhibits
quantitative determination of the relaxation time scale. Droplet coalescence was
simulated using a computational framework to validate both experimental
approaches. The results indicate that time-dependent monitoring of droplet shape
from the EBL intensity allows for robust determination of properties such as
surface tension and viscosity. Finally, the potential of high frame rate imaging
to examine the coalescence of dissimilar viscosity droplets is discussed.
PMID- 27497561
TI - A theoretical study of the relaxation of a phenyl group chemisorbed to an RDX
freestanding thin film.
AB - Energy relaxation from an excited phenyl group chemisorbed to the surface of a
crystalline thin film of alpha-1,3,5-trinitro-1,3,5-triazacyclohexane (alpha-RDX)
at 298 K and 1 atm is simulated using molecular dynamics. Two schemes are used to
excite the phenyl group. In the first scheme, the excitation energy is added
instantaneously as kinetic energy by rescaling momenta of the 11 atoms in the
phenyl group. In the second scheme, the phenyl group is equilibrated at a higher
temperature in the presence of static RDX geometries representative of the 298 K
thin film. An analytical model based on ballistic phonon transport that requires
only the harmonic part of the total Hamiltonian and includes no adjustable
parameters is shown to predict, essentially quantitatively, the short-time
dynamics of the kinetic energy relaxation (~200 fs). The dynamics of the phenyl
group for times longer than about 6 ps follows exponential decay and agrees
qualitatively with the dynamics described by a master equation. Long-time heat
propagation within the bulk of the crystal film is consistent with the heat
equation.
PMID- 27497562
TI - Complete equation of state for shocked liquid nitrogen: Analytical developments.
AB - The thermodynamic response of liquid nitrogen has been studied extensively, in
part, due to the long-standing interest in the high pressure and high temperature
dissociation of shocked molecular nitrogen. Previous equation of state (EOS)
developments regarding shocked liquid nitrogen have focused mainly on the use of
intermolecular pair potentials in atomistic calculations. Here, we present EOS
developments for liquid nitrogen, incorporating analytical models, for use in
continuum calculations of the shock compression response. The analytical models,
together with available Hugoniot data, were used to extrapolate a low pressure
reference EOS for molecular nitrogen [R. Span et al., J. Phys. Chem. Ref. Data
29, 1361 (2000)] to high pressures and high temperatures. Using the EOS presented
here, the calculated pressures and temperatures for single shock, double shock,
and multiple shock compression of liquid nitrogen provide a good match to the
measured results over a broad range of P-T space. These calculations provide the
first comparison of EOS developments with recently measured P-T states under
multiple shock compression. The present EOS developments are general and are
expected to be useful for other liquids that have low pressure reference EOS
information available.
PMID- 27497563
TI - A comprehensive scenario of the thermodynamic anomalies of water using the
TIP4P/2005 model.
AB - The striking behavior of water has deserved it to be referred to as an
"anomalous" liquid. The water anomalies are greatly amplified in metastable
(supercooled and/or stretched) regions. This makes difficult a complete
experimental description since, beyond certain limits, the metastable phase
necessarily transforms into the stable one. Theoretical interpretation of the
water anomalies could then be based on simulation results of well validated water
models. But the analysis of the simulations has not yet reached a consensus. In
particular, one of the most popular theoretical scenarios-involving the existence
of a liquid-liquid critical point (LLCP)-is disputed by several authors. In this
work, we propose to use a number of exact thermodynamic relations which may shed
light on this issue. Interestingly, these relations may be tested in a region of
the phase diagram which is outside the LLCP thus avoiding the problems associated
to the coexistence region. The central property connected to other water
anomalies is the locus of temperatures at which the density along isobars attain
a maximum (TMD line) or a minimum (TmD). We have performed computer simulations
to evaluate the TMD and TmD for a successful water model, namely, TIP4P/2005. We
have also evaluated the vapor-liquid (VL) spinodal in the region of large
negative pressures. The shape of these curves and their connection to the extrema
of some response functions, in particular the isothermal compressibility and heat
capacity at constant pressure, provides very useful information which may help to
elucidate the validity of the theoretical proposals. In this way, we are able to
present for the first time a comprehensive scenario of the thermodynamic water
anomalies for TIP4P/2005 and their relation to the vapor-liquid spinodal. The
overall picture shows a remarkable similarity with the corresponding one for the
ST2 water model, for which the existence of a LLCP has been demonstrated in
recent years. It also provides a hint as to where the long-sought for extrema in
response functions might become accessible to experiments.
PMID- 27497564
TI - Anomalous properties and the liquid-liquid phase transition in gallium.
AB - A group of materials including water and silicon exhibit many anomalous
behaviors, e.g., density anomaly and diffusivity anomaly (increase upon
compression). These materials are hypothesized to have a liquid-liquid phase
transition (LLPT) and the critical fluctuation in the vicinity of the liquid
liquid critical point is considered as the origin of different anomalies. Liquid
gallium was also reported to have a LLPT, yet whether it shows similar water-like
anomalies is not yet studied. Using molecular dynamics simulations on a modified
embedded-atom model, we study the thermodynamic, dynamic, and structural
properties of liquid gallium as well as its LLPT. We find that, similar to water
like materials predicted to have the LLPT, gallium also shows different anomalous
behaviors (e.g., density anomaly, diffusivity anomaly, and structural anomaly).
We also find that its thermodynamic and structural response functions are
continuous and show maxima in the supercritical region, the loci of which
asymptotically approach to the other and merge to the Widom line. These phenomena
are consistent with the supercritical phenomenon in a category of materials with
a liquid-liquid critical point, which could be common features in most materials
with a LLPT.
PMID- 27497565
TI - Emergence of linear elasticity from the atomistic description of matter.
AB - We investigate the emergence of the continuum elastic limit from the atomistic
description of matter at zero temperature considering how locally defined elastic
quantities depend on the coarse graining length scale. Results obtained
numerically investigating different model systems are rationalized in a unifying
picture according to which the continuum elastic limit emerges through a process
determined by two system properties, the degree of disorder, and a length scale
associated to the transverse low-frequency vibrational modes. The degree of
disorder controls the emergence of long-range local shear stress and shear strain
correlations, while the length scale influences the amplitude of the fluctuations
of the local elastic constants close to the jamming transition.
PMID- 27497566
TI - A dissolution-precipitation mechanism is at the origin of concrete creep in moist
environments.
AB - Long-term creep (i.e., deformation under sustained load) is a significant
material response that needs to be accounted for in concrete structural design.
However, the nature and origin of concrete creep remain poorly understood and
controversial. Here, we propose that concrete creep at relative humidity >= 50%,
but fixed moisture content (i.e., basic creep), arises from a dissolution
precipitation mechanism, active at nanoscale grain contacts, as has been
extensively observed in a geological context, e.g., when rocks are exposed to
sustained loads, in liquid-bearing environments. Based on micro-indentation and
vertical scanning interferometry data and molecular dynamics simulations carried
out on calcium-silicate-hydrate (C-S-H), the major binding phase in concrete, of
different compositions, we show that creep rates are correlated with dissolution
rates-an observation which suggests a dissolution-precipitation mechanism as
being at the origin of concrete creep. C-S-H compositions featuring high
resistance to dissolution, and, hence, creep are identified. Analyses of the
atomic networks of such C-S-H compositions using topological constraint theory
indicate that these compositions present limited relaxation modes on account of
their optimally connected (i.e., constrained) atomic networks.
PMID- 27497567
TI - Pseudogap and anharmonic phonon behavior in Ba8Ga16Ge30: An NMR study.
AB - We have performed (69)Ga, (71)Ga, and (137)Ba NMR on Ba8Ga16Ge30, a clathrate
semiconductor which has been of considerable interest due to its large figure of
merit for thermoelectric applications. In measurements from 4 K to 450 K, we used
measurements on the two Ga nuclei to separate the magnetic and electric
quadrupole hyperfine contributions and thereby gain information about the
metallic and phonon behavior. The results show the presence of a pseudogap in the
Ga electronic states within the conduction band, superposed upon a large Ba
contribution to the conduction band. Meanwhile the phonon contributions to the Ga
relaxation rates are large and increase more rapidly with temperature than
typical semiconductors. These results provide evidence for enhanced anharmonicity
of the propagative phonon modes over a wide range, providing experimental
evidence for enhanced phonon-phonon scattering as a mechanism for the reduced
thermal conductivity.
PMID- 27497568
TI - Left-right correlation in coupled F-center defects.
AB - This work explores how left-right correlation, a textbook problem in electronic
structure theory, manifests in a textbook example of electrons trapped in crystal
defects. I show that adjacent F-center defects in lithium fluoride display
symptoms of "strong" left-right correlation, symptoms similar to those seen in
stretched H2. Simulations of UV/visible absorption spectra qualitatively fail to
reproduce experiment unless left-right correlation is taken into account. This is
of interest to both the electronic structure theory and crystal-defect
communities. Theorists have a new well-behaved system to test their methods.
Crystal-defect groups are cautioned that the approximations that successfully
model single F-centers may fail for adjacent F-centers.
PMID- 27497569
TI - Buckling failure of square ice-nanotube arrays constrained in graphene
nanocapillaries.
AB - Graphene confinement provides a new physical and mechanical environment with
ultrahigh van der Waals pressure, resulting in new quasi-two-dimensional phases
of few-layer ice. Polymorphic transition can occur in bilayer constrained
water/ice system. Here, we perform a comprehensive study of the phase transition
of AA-stacked bilayer water constrained within a graphene nanocapillary. The
compression-limit and superheating-limit (phase) diagrams are obtained, based on
the extensive molecular-dynamics simulations at numerous thermodynamic states.
Liquid-to-solid, solid-to-solid, and solid-to-liquid-to-solid phase transitions
are observed in the compression and superheating of bilayer water. Interestingly,
there is a temperature threshold (~275 K) in the compression-limit diagram, which
indicates that the first-order and continuous-like phase transitions of bilayer
water depend on the temperature. Two obviously different physical processes,
compression and superheating, display similar structural evolution; that is,
square ice-nanotube arrays (BL-VHDI) will bend first and then transform into
bilayer triangular AA stacking ice (BL-AAI). The superheating limit of BL-VHDI
exhibits local maxima, while that of BL-AAI increases monotonically. More
importantly, from a mechanics point of view, we propose a novel mechanism of the
transformation from BL-VHDI to BL-AAI, both for the compression and superheating
limits. This structural transformation can be regarded as the "buckling failure"
of the square-ice-nanotube columns, which is dominated by the lateral pressure.
PMID- 27497570
TI - Vibrational spectroscopic evidence for (NO)3 formation on Cu(111).
AB - The formation of (NO)3 on Cu(111) was recently reported based on scanning
tunneling microscopy observations [A. Shiotari et al., J. Chem. Phys. 141, 134705
(2014)]. We herein report studies into this system using electron energy loss
spectroscopy and verify the above findings through vibrational analysis. For the
surface covered with mixed isotopes of N(16)O and N(18)O, we observed four peaks
corresponding to N-O stretching vibrations, which were ascribed to the four
isotopic combinations of the trimer. Dynamic coupling within the trimer was
evaluated from model calculations of the coupled oscillators. Furthermore, we
observed hindered rotation and translation modes in the dipole scattering regime,
suggesting that the molecular axis is tilted from the surface normal. These
results provide spectroscopic support for the formation of (NO)3 on Cu(111).
PMID- 27497572
TI - Role of density modulation in the spatially resolved dynamics of strongly
confined liquids.
AB - Confinement by walls usually produces a strong modulation in the density of dense
liquids near the walls. Using molecular dynamics simulations, we examine the
effects of the density modulation on the spatially resolved dynamics of a liquid
confined between two parallel walls, using a resolution of a fraction of the
interparticle distance in the liquid. The local dynamics is quantified by the
relaxation time associated with the temporal autocorrelation function of the
local density. We find that this local relaxation time varies in phase with the
density modulation. The amplitude of the spatial modulation of the relaxation
time can be quite large, depending on the characteristics of the wall and
thermodynamic parameters of the liquid. To disentangle the effects of confinement
and density modulation on the spatially resolved dynamics, we compare the
dynamics of a confined liquid with that of an unconfined one in which a similar
density modulation is induced by an external potential. We find several
differences indicating that density modulation alone cannot account for all the
features seen in the spatially resolved dynamics of confined liquids. We also
examine how the dynamics near a wall depends on the separation between the two
walls and show that the features seen in our simulations persist in the limit of
large wall separation.
PMID- 27497573
TI - Enhancement factor statistics of surface enhanced Raman scattering in multiscale
heterostructures of nanoparticles.
AB - Suitable metal nanostructures may induce surface-enhanced Raman scattering (SERS)
enhancement factors (EFs) large-enough to reach single-molecule sensitivity.
However, the gap hot-spot EF probability density function (PDF) has the character
of a long-tail distribution, which dramatically mines the reproducibility of SERS
experiments. Herein, we carry out electrodynamic calculations based on a 3D
finite element method of two plasmonic nanostructures, combined with Monte Carlo
simulations of the EF statistics under different external conditions. We compare
the PDF produced by a homodimer of nanoparticles with that provided by a self
similar trimer. We show that the PDF is sensitive to the spatial distribution of
near-field enhancement specifically supported by the nanostructure geometry.
Breaking the symmetry of the plasmonic system is responsible for inducing
particular modulations of the PDF tail resembling a multiple Poisson
distribution. We also study the influence that molecular diffusion towards the
hottest hot-spot, or selective hot-spot targeting, might have on the EF PDF. Our
results quantitatively assess the possibility of designing the response of a SERS
substrate so as to contain the intrinsic EF PDF variance and significantly
improving, in principle, the reproducibility of SERS experiments.
PMID- 27497571
TI - Dependence of SERS enhancement on the chemical composition and structure of Ag/Au
hybrid nanoparticles.
AB - Noble metal nanoparticles (NPs) such as silver (Ag) and gold (Au) have unique
plasmonic properties that give rise to surface enhanced Raman scattering (SERS).
Generally, Ag NPs have much stronger plasmonic properties and, hence, provide
stronger SERS signals than Au NPs. However, Ag NPs lack the chemical stability
and biocompatibility of comparable Au NPs and typically exhibit the most intense
plasmonic resonance at wavelengths much shorter than the optimal spectral region
for many biomedical applications. To overcome these issues, various experimental
efforts have been devoted to the synthesis of Ag/Au hybrid NPs for the purpose of
SERS detections. However, a complete understanding on how the SERS enhancement
depends on the chemical composition and structure of these nanoparticles has not
been achieved. In this study, Mie theory and the discrete dipole approximation
have been used to calculate the plasmonic spectra and near-field electromagnetic
enhancements of Ag/Au hybrid NPs. In particular, we discuss how the
electromagnetic enhancement depends on the mole fraction of Au in Ag/Au alloy NPs
and how one may use extinction spectra to distinguish between Ag/Au alloyed NPs
and Ag-Au core-shell NPs. We also show that for incident laser wavelengths
between ~410 nm and 520 nm, Ag/Au alloyed NPs provide better electromagnetic
enhancement than pure Ag, pure Au, or Ag-Au core-shell structured NPs. Finally,
we show that silica-core Ag/Au alloy shelled NPs provide even better performance
than pure Ag/Au alloy or pure solid Ag and pure solid Au NPs. The theoretical
results presented will be beneficial to the experimental efforts in optimizing
the design of Ag/Au hybrid NPs for SERS-based detection methods.
PMID- 27497575
TI - On the determination of the crystal-vapor surface free energy, and why a Gaussian
expression can be accurate for a system far from Gaussian.
AB - The crystal-vapor surface free energy gamma is an important physical parameter
governing physical processes, such as wetting and adhesion. We explore exact and
approximate routes to calculate gamma based on cleaving an intact crystal into
non-interacting sub-systems with crystal-vapor interfaces. We do this by turning
off the interactions, DeltaV, between the sub-systems. Using the soft-core scheme
for turning off DeltaV, we find that the free energy varies smoothly with the
coupling parameter lambda, and a single thermodynamic integration yields the
exact gamma. We generate another exact method, and a cumulant expansion for gamma
by expressing the surface free energy in terms of an average of e(-betaDeltaV) in
the intact crystal. The second cumulant, or Gaussian approximation for gamma is
surprisingly accurate in most situations, even though we find that the underlying
probability distribution for DeltaV is clearly not Gaussian. We account for this
fact by developing a non-Gaussian theory for gamma and find that the difference
between the non-Gaussian and Gaussian expressions for gamma consist of terms that
are negligible in many situations. Exact and approximate methods are applied to
the (111) surface of a Lennard-Jones crystal and are also tested for more complex
molecular solids, the surface of octane and nonadecane. Alkane surfaces were
chosen for study because their crystal-vapor surface free energy has been of
particular interest for understanding surface freezing in these systems.
PMID- 27497574
TI - Vibrational energy transfer near a dissociative adsorption transition state:
State-to-state study of HCl collisions at Au(111).
AB - In this work we seek to examine the nature of collisional energy transfer between
HCl and Au(111) for nonreactive scattering events that sample geometries near the
transition state for dissociative adsorption by varying both the vibrational and
translational energy of the incident HCl molecules in the range near the
dissociation barrier. Specifically, we report absolute vibrational excitation
probabilities for HCl(v = 0 -> 1) and HCl(v = 1 -> 2) scattering from clean
Au(111) as a function of surface temperature and incidence translational energy.
The HCl(v = 2 -> 3) channel could not be observed-presumably due to the onset of
dissociation. The excitation probabilities can be decomposed into adiabatic and
nonadiabatic contributions. We find that both contributions strongly increase
with incidence vibrational state by a factor of 24 and 9, respectively. This
suggests that V-T as well as V-EHP coupling can be enhanced near the transition
state for dissociative adsorption at a metal surface. We also show that
previously reported HCl(v = 0 -> 1) excitation probabilities [Q. Ran et al.,
Phys. Rev. Lett. 98, 237601 (2007)]-50 times smaller than those reported here
were influenced by erroneous assignment of spectroscopic lines used in the data
analysis.
PMID- 27497576
TI - Designing convex repulsive pair potentials that favor assembly of kagome and snub
square lattices.
AB - Building on a recently introduced inverse strategy, isotropic and convex
repulsive pair potentials were designed that favor assembly of particles into
kagome and equilateral snub square lattices. The former interactions were
obtained by a numerical solution of a variational problem that maximizes the
range of density for which the ground state of the potential is the kagome
lattice. Similar optimizations targeting the snub square lattice were also
carried out, employing a constraint that required a minimum chemical potential
advantage of the target over select competing structures. This constraint helped
to discover isotropic interactions that meaningfully favored the snub square
lattice as the ground state structure despite the asymmetric spatial distribution
of particles in its coordination shells and the presence of tightly competing
structures. Consistent with earlier published results [W. Pineros et al., J.
Chem. Phys. 144, 084502 (2016)], enforcement of greater chemical potential
advantages for the target lattice in the interaction optimization led to
assemblies with enhanced thermal stability.
PMID- 27497577
TI - Stabilizing the hexagonal close packed structure of hard spheres with polymers:
Phase diagram, structure, and dynamics.
AB - We study the phase behaviour of a binary mixture of colloidal hard spheres and
freely jointed chains of beads using Monte Carlo simulations. Recently
Panagiotopoulos and co-workers predicted [Nat. Commun. 5, 4472 (2014)] that the
hexagonal close packed (HCP) structure of hard spheres can be stabilized in such
a mixture due to the interplay between polymer and the void structure in the
crystal phase. Their predictions were based on estimates of the free-energy
penalty for adding a single hard polymer chain in the HCP and the competing face
centered cubic (FCC) phase. Here we calculate the phase diagram using free-energy
calculations of the full binary mixture and find a broad fluid-solid coexistence
region and a metastable gas-liquid coexistence region. For the colloid-monomer
size ratio considered in this work, we find that the HCP phase is only stable in
a small window at relatively high polymer reservoir packing fractions, where the
coexisting HCP phase is nearly close packed. Additionally we investigate the
structure and dynamic behaviour of these mixtures.
PMID- 27497578
TI - Effect of five-membered ring and heteroatom substitution on charge transport
properties of perylene discotic derivatives: A theoretical approach.
AB - Density functional theory calculations were carried out to investigate the
evolvement of charge transport properties of a set of new discotic systems as a
function of ring and heteroatom (B, Si, S, and Se) substitution on the basic
structure of perylene. The replacement of six-membered rings by five-membered
rings in the reference compound has shown a prominent effect on the electron
reorganization energy that decreases ~0.2 eV from perylene to the new carbon five
membered ring derivative. Heteroatom substitution with boron also revealed to
lower the LUMO energy level and increase the electron affinity, therefore
lowering the electron injection barrier compared to perylene. Since the rate of
the charge transfer between two molecules in columnar discotic systems is
strongly dependent on the orientation of the stacked cores, the total energy and
transfer integral of a dimer as a disc is rotated with respect to the other along
the stacking axis have been predicted. Aimed at obtaining a more realistic
approach to the bulk structure, the molecular geometry of clusters made up of
five discs was fully optimized, and charge transfer rate and mobilities were
estimated for charge transport along a one dimensional pathway. Heteroatom
substitution with selenium yields electron transfer integral values ~0.3 eV with
a relative disc orientation of 25 degrees , which is the preferred angle
according to the dimer energy profile. All the results indicate that the
tetraselenium-substituted derivative, not synthetized so far, could be a
promising candidate among those studied in this work for the fabrication of n
type semiconductors based on columnar discotic liquid crystals materials.
PMID- 27497579
TI - Comment on "Replica-exchange-with-tunneling for fast exploration of protein
landscapes" [J. Chem. Phys. 143, 224102 (2015)].
AB - In "Replica-exchange-with-tunneling for fast exploration of protein landscapes"
[F. Yasar et al., J. Chem. Phys. 143, 224102 (2015)], a novel sampling algorithm
called "Replica Exchange with Tunneling" was proposed. However, due to its
violation of the detailed balance, the algorithm fails to sample from the correct
canonical ensemble.
PMID- 27497580
TI - Response to "Comment on 'Replica-exchange-with-tunneling for fast exploration of
protein landscapes"' [J. Chem. Phys. 145, 057101 (2016)].
PMID- 27497581
TI - Erratum: "Van der Waals supercritical fluid: Exact formulas for special lines"
[J. Chem. Phys. 135, 084503 (2011)].
PMID- 27497582
TI - Publisher's Note: "Permeation of the three aromatic dipeptides through lipid
bilayers: Experimental and computational study" [J. Chem. Phys. 144, 245103
(2016)].
PMID- 27497583
TI - Erratum: "Ionic strength independence of charge distributions in solvation of
biomolecules" [J. Chem. Phys. 141, 22D503 (2014)].
PMID- 27497584
TI - Cytogenetics of the Thorny Catfish Trachydoras paraguayensis (Eigenmann & Ward,
1907), (Siluriformes, Doradidae): Evidence of Pericentric Inversions and
Chromosomal Fusion.
AB - The karyotype and chromosomal characteristics of Trachydorasparaguayensis, a
representative of the South American catfish family Doradidae, were analyzed by
conventional (Giemsa staining, silver staining, C-banding) and molecular (FISH
with rDNA and telomeric probes) cytogenetic techniques. The diploid chromosome
number was 2n = 56, with 36 metacentric, 16 submetacentric, and 4 subtelocentric
chromosomes in both sexes; however, a remarkable heteromorphism in pair 22
(submetacentric and metacentric elements) was detected in 6 individuals. Compared
to other representatives of Doradidae which mostly have 58 chromosomes, the
karyotype of T. paraguayensis suggests a reduction in 2n due to chromosomal
fusion, as could be deduced from the presence of an interstitial telomere
sequence in the submetacentric pair 19. Pale heterochromatic blocks were present
in the terminal regions of some chromosomes, very similar to other species of
Doradidae. The interstitial position of the NORs observed in the karyotype of T.
paraguayensis differs from those reported for most Doradidae species, indicating
that it is a derived character. FISH with 5S rDNA revealed 2 interstitial
fluorescent signals in the submetacentric pair 22, and the polymorphism of these
sites likely resulted from a pericentric inversion.
PMID- 27497585
TI - Pollutant formation in the pyrolysis and combustion of Automotive Shredder
Residue.
AB - The present work has been carried out to verify the feasibility of thermal
valorization of an automobile shredder residue (ASR). With this aim, the thermal
decomposition of this waste has been studied in a laboratory scale reactor,
analyzing the pollutants emitted under different operating conditions. The
emission factors of carbon oxides, light hydrocarbons, PAHs, PCPhs, PCBzs, PBPhs,
PCDD/Fs, dioxin-like PCBs and PBDD/Fs were determined at two temperatures, 600
and 850 degrees C, and under different oxygen ratios ranging from 0 (pure
pyrolysis) to 1.5 (over-stoichiometric oxidation). After analyzing all these
compounds, we conclude that thermal valorization of ASR is a clean way to treat
this waste.
PMID- 27497586
TI - A novel approach in calculating site-specific aftercare completion criteria for
landfills in The Netherlands: Policy developments.
AB - As part of a more circular economy, current attention on waste is shifting from
landfilling towards the prevention, re-use and recycling of waste materials.
Although the need for landfills is decreasing, there are many landfills around
the world that are still operational or at the point of starting the aftercare
period. With traditional aftercare management, these landfills require perpetual
aftercare at considerable cost due to monitoring and regular maintenance of
liners. In an attempt to lower these aftercare costs, and to prevent that future
generations become responsible for finding a sustainable solution of present day
waste, the Dutch government takes action to explore the possibilities of
sustainable landfill management. A project was started to investigate whether the
use of source-oriented treatment techniques (so-called active treatment) of
landfills can result in a sustainable emission reduction to soil and groundwater.
During the next decade, sustainable landfill management is tested at three
selected pilot landfills in the Netherlands. To enable this pilot testing and to
determine its success after the experimental treatment period, a new methodology
and conceptual framework was developed. The aim of this paper is to describe the
development of the new methodology, and in particular the policy decisions,
needed to determine whether the pilot experiments will be successful. The pilot
projects are considered successful when the concentrations in the leachate of the
pilot landfills have sufficiently been reduced and for longer periods of time and
comply with the derived site-specific Environmental Protection Criteria (EPC). In
that case, aftercare can be reduced, and it can be determined whether sustainable
landfill management is economically feasible for further implementation.
PMID- 27497587
TI - Consecutive anaerobic-aerobic treatment of the organic fraction of municipal
solid waste and lignocellulosic materials in laboratory-scale landfill
bioreactors.
AB - The scope of this study is to evaluate the use of laboratory-scale landfill
bioreactors, operated consecutively under anaerobic and aerobic conditions, for
the combined treatment of the organic fraction of municipal solid waste (OFMSW)
with two different co-substrates of lignocellulosic nature, namely green waste
(GW) and dried olive pomace (DOP). According to the results such a system would
represent a promising option for eventual larger scale applications. Similar
variation patterns among bioreactors indicate a relatively defined sequence of
processes. Initially operating the systems under anaerobic conditions would allow
energetic exploitation of the substrates, while the implementation of a leachate
treatment system ultimately aiming at nutrient recovery, especially during the
anaerobic phase, could be a profitable option for the whole system, due to the
high organic load that characterizes this effluent. In order to improve the
overall effectiveness of such a system, measures towards enhancing methane
contents of produced biogas, such as substrate pretreatment, should be
investigated. Moreover, the subsequent aerobic phase should have the goal of
stabilizing the residual materials and finally obtain an end material eventually
suitable for other purposes.
PMID- 27497588
TI - Understanding biofilm formation in intravascular device-related infections.
PMID- 27497589
TI - The ten wishes and hopes of the deputy editors of Intensive Care Medicine.
PMID- 27497590
TI - Relative importance of local habitat complexity and regional factors for
assemblages of oribatid mites (Acari: Oribatida) in Sphagnum peat bogs.
AB - We investigated communities of oribatid mites in five peat bogs in the north-west
of the East European plain. We aimed to determine the extent to which geographic
factors (latitude, separation distance), local environment (Sphagnum moss
species, ground water level, biogeochemistry) and local habitat complexity
(diversity of vascular plants and bryophytes in the surrounding plant community)
influence diversity and community composition of Oribatida. There was a
significant north-to-south increase in Oribatida abundance. In the variance
partitioning, spatial factors explained 33.1 % of variability in abundance across
samples; none of the environmental factors were significant. Across all bogs,
Oribatida species richness and community composition were similar in Sphagnum
rubellum and Sphagnum magellanicum, but significantly different and less diverse
in Sphagnum cuspidatum. Sphagnum microhabitat explained 52.2 % of variability in
Oribatida species richness, whereas spatial variables explained only 8.7 %. There
was no distance decay in community similarity between bogs with increased
geographical distance. The environmental variables explained 34.9 % of the
variance in community structure, with vascular plants diversity, bryophytes
diversity, and ground water level all contributing significantly; spatial
variables explained 15.1 % of the total variance. Overall, only 50 % of the
Oribatida community variance was explained by the spatial structure and
environmental variables. We discuss relative importance of spatial and local
environmental factors, and make general inferences about the formation of fauna
in Sphagnum bogs.
PMID- 27497591
TI - Field application of menthol for Japanese honey bees, Apis cerana japonica
(Hymenoptera: Apidae), to control tracheal mites, Acarapis woodi (Acari:
Tarsonemidae).
AB - The first record of tracheal mites, Acarapis woodi, in Japan was made in 2010.
These mites have since caused serious damage to the colonies of Japanese honey
bees, Apis cerana japonica. In the present study, to control the mites on
Japanese honey bees with l-menthol, an agent used for European honey bees, Apis
mellifera, we investigated (1) the seasonality of menthol efficacy, (2) the
overwintering mortality of menthol-treated colonies, and (3) the menthol residue
in honey under field conditions in cooperation with private beekeepers of
Japanese honey bees. Seasonal menthol efficacy was tested by applying 30 g of l
menthol for 1 month in different seasons. Mite prevalence was measured by
dissecting the honey bee thorax. Overwintering mortality was monitored during
winter after checking the mite prevalence in autumn, and was compared with that
of untreated colonies reported in our previous study. The residual level of
menthol in honey was measured by GC-MS. The results showed that the menthol
treated colonies had a smaller rate of increase in mite prevalence than the
untreated colonies. The effects of menthol were highest in March and April. The
winter mortality was depressed by menthol treatment. Honey samples extracted from
the menthol-treated colonies included 0.4 ppm of menthol residue on average. Our
findings suggest that menthol treatment is effective for controlling the tracheal
mites on Japanese honey bees.
PMID- 27497592
TI - Biological and life table parameters of Typhlodromus laurentii and Iphiseius
degenerans (Acari, Phytoseiidae) fed on Panonychus citri and pollen of Oxalis pes
caprae under laboratory conditions.
AB - Typhlodromus laurentii and Iphiseius degenerans are two generalist phytoseiid
mites, broadly spread in the Mediterranean area, especially in citrus orchards.
In the present work we report results on various biological and life table
parameters of the two phytoseiids, fed on pollen of Oxalis pes-caprae and various
stages of the tetranychid Panonychus citri. Iphiseius degenerans had the shortest
post embryonic development (6.53 days), the highest oviposition rate (1.83
eggs/female/day) and the shortest mean time between eggs laid (0.55 day) on
Oxalis pollen, whereas the two food types did not influence these parameters in
T. laurentii. However, Oxalis pollen showed a positive effect on the survivorship
of the latter phytoseiid, with a median life time (LT50) of 44.51 days, which was
two times longer than that registered on prey with the same phytoseiid, and on
both food types with I. degenerans. This latter species had a better performance
on the pollen (rm = 0.243, lambda = 1.275, Ro = 22.88, DT = 2.85) than on prey
(rm = 0.182, lambda = 1.199, Ro = 17.43, DT = 3.81). On the other hand, the
pollen influenced the net reproductive rate (25.43 females/female) of T.
laurentii positively but showed the same effect as the prey on the other
demographic parameters. Our results improve knowledge on the feeding behaviour of
the above mentioned phytoseiids on two food sources that could represent the main
possibility to maintain a consistent population of these predators during winter.
Moreover, both phytoseiids were shown to be good biocontrol candidates of P.
citri populations.
PMID- 27497593
TI - Differential deviant probability effects on two hierarchical levels of the
auditory novelty system.
AB - Deviance detection is a key functional property of the auditory system that
allows pre-attentive discrimination of incoming stimuli not conforming to a rule
extracted from the ongoing constant stimulation, thereby proving that
regularities in the auditory scene have been encoded in the auditory system.
Using simple-feature stimulus deviations, regularity encoding and deviance
detection have been reported in brain responses at multiple latencies of the
human Auditory Evoked Potential (AEP), such as the Mismatch Negativity (MMN;
peaking at 100-250ms from stimulus onset) and Middle-Latency Responses (MLR;
peaking at 12-50ms). More complex levels of regularity violations, however, are
only indexed by AEPs generated at higher stages of the auditory system,
suggesting a hierarchical organization in the encoding of auditory regularities.
The aim of the current study is to further characterize the auditory hierarchy of
novelty responses, by assessing the sensitivity of MLR components to deviant
probability manipulations. MMNs and MLRs were recorded in 24 healthy
participants, using an oddball location paradigm with three different deviant
probabilities (5%, 10% and 20%), and a reversed-standard (91.5%). We analyzed
differences in the MLRs elicited to each of the deviant stimuli and the reversed
standard, as well as within deviant stimuli. Our results confirmed deviance
detection at the level of both MLRs and MMN, but significant differences for
deviant probabilities were found only for the MMN. These results suggest a
functional dissociation between regularity encoding, already present at early
stages of auditory processing, and the encoding of the probability with which
this regularity is disrupted, which is only processed at higher stages of the
auditory hierarchy.
PMID- 27497594
TI - Advanced metal artifact reduction MRI of metal-on-metal hip resurfacing
arthroplasty implants: compressed sensing acceleration enables the time-neutral
use of SEMAC.
AB - OBJECTIVE: Compressed sensing (CS) acceleration has been theorized for slice
encoding for metal artifact correction (SEMAC), but has not been shown to be
feasible. Therefore, we tested the hypothesis that CS-SEMAC is feasible for MRI
of metal-on-metal hip resurfacing implants. MATERIALS AND METHODS: Following
prospective institutional review board approval, 22 subjects with metal-on-metal
hip resurfacing implants underwent 1.5 T MRI. We compared CS-SEMAC prototype,
high-bandwidth TSE, and SEMAC sequences with acquisition times of 4-5, 4-5 and 10
12 min, respectively. Outcome measures included bone-implant interfaces, image
quality, periprosthetic structures, artifact size, and signal- and contrast-to
noise ratios (SNR and CNR). Using Friedman, repeated measures analysis of
variances, and Cohen's weighted kappa tests, Bonferroni-corrected p-values of
0.005 and less were considered statistically significant. RESULTS: There was no
statistical difference of outcomes measures of SEMAC and CS-SEMAC images.
Visibility of implant-bone interfaces and pseudocapsule as well as fat
suppression and metal reduction were "adequate" to "good" on CS-SEMAC and "non
diagnostic" to "adequate" on high-BW TSE (p < 0.001, respectively). SEMAC and CS
SEMAC showed mild blur and ripple artifacts. The metal artifact size was 63 %
larger for high-BW TSE as compared to SEMAC and CS-SEMAC (p < 0.0001,
respectively). CNRs were sufficiently high and statistically similar, with the
exception of CNR of fluid and muscle and CNR of fluid and tendon, which were
higher on intermediate-weighted high-BW TSE (p < 0.005, respectively).
CONCLUSION: Compressed sensing acceleration enables the time-neutral use of SEMAC
for MRI of metal-on-metal hip resurfacing implants when compared to high-BW TSE
and image quality similar to conventional SEMAC.
PMID- 27497595
TI - Performance of self-collected penile-meatal swabs compared to clinician-collected
urethral swabs for the detection of Chlamydia trachomatis, Neisseria gonorrhoeae,
Trichomonas vaginalis, and Mycoplasma genitalium by nucleic acid amplification
assays.
AB - Men were enrolled in a study to assess the performance and acceptability of self
collected penile meatal swabs as compared to clinician-collected urethral swabs
for sexually transmitted infections (STIs). We expected penile-meatal swabs to
perform favorably to urethral swabs for Chlamydia trachomatis (CT), Neisseria
gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG)
detection by nucleic acid amplification assays (NAATs). Of 203 swab pairs tested;
for CT, penile-meatal swab sensitivity was 96.8% and specificity was 98.8%. NG
sensitivity and specificity were 100% and 98.9%, respectively. For TV,
sensitivity was 85.0% and specificity was 96.7%. For MG sensitivity and
specificity were 79.3% and 99.4%, respectively. No significant statistical
differences between sample type accuracy (CT: P=0.625; NG: P=0.248; TV: P=0.344;
and MG: P=0.070) existed. Most men, 90.1%, reported self-collection of penile
meatal swabs as "Very Easy" or "Easy". Self-collected penile-meatal swabs
appeared acceptable for NAAT STI detection and an acceptable collection method by
men.
PMID- 27497596
TI - Exploring Olfactory Function and Its Relation with Behavioral and Cognitive
Impairment in Amyotrophic Lateral Sclerosis Patients: A Cross-Sectional Study.
AB - BACKGROUND: Behavioral and cognitive impairment are common in amyotrophic lateral
sclerosis (ALS) and represent a continuum with frontotemporal dementia (FTD).
Olfactory dysfunction has been described in a subset of ALS patients and might be
associated with frontotemporal and insular cortex dysfunction. OBJECTIVE: To
evaluate olfaction dysfunction in ALS patients and its relationship with either
cognition or behavioral impairment. METHODS: 28 consecutive ALS patients
underwent an extensive cognitive and behavioral battery and were classified as
patients with normal cognition (ALS-N, n = 11) or with part of the ALS-FTD
spectrum (n = 17), including either cognitive or behavioral impairment or
dementia. Odor verbal and visual identification and discrimination were
investigated in patients and age-matched controls using a test adapted from the
Sniffin' Sticks. RESULTS: Olfactory function was significantly different between
ALS-FTD spectrum patients and controls (p < 0.001) and inversely correlated with
behavioral and cognitive performance. The 10-point cutoff distinguished ALS-N
from ALS-FTD spectrum patients with a sensitivity and specificity of 71 and 100%,
respectively. CONCLUSIONS: Hyposmia is common in a subset of ALS patients and
strongly associated with behavioral and cognitive impairment. Olfactory testing
may represent an early screening tool in order to identify ALS subjects with
cognitive/behavioral dysfunction. Further studies in larger series are mandatory
in order to better investigate clinical and pathological aspects in this group of
patients.
PMID- 27497598
TI - Regulation of mitochondrial metabolism during hibernation by reversible
suppression of electron transport system enzymes.
AB - Small hibernators cycle between periods of torpor, with body temperature (T b)
approximately 5 degrees C, and interbout euthermia (IBE), where T b is
approximately 37 degrees C. During entrance into a torpor bout liver
mitochondrial respiration is rapidly suppressed by 70 % relative to IBE. We
compared activities of electron transport system (ETS) complexes in intact liver
mitochondria isolated from 13-lined ground squirrels (Ictidomys tridecemlineatus)
sampled during torpor and IBE to investigate potential sites of this reversible
metabolic suppression. Flux through complexes I-IV and II-IV was suppressed by 40
and 60 %, respectively, in torpor, while flux through complexes III-IV and IV did
not differ between torpor and IBE. We also measured maximal enzyme activity of
ETS enzymes in homogenized isolated mitochondria and whole liver tissue. In
isolated mitochondria, activities of complexes I and II were significantly lower
in torpor relative to IBE, but complexes III, IV, and V did not differ. In liver
tissue, only activity of complex II was suppressed during torpor relative to IBE.
Despite the significant differences in both ETS flux and maximal activity, the
protein content of complexes I and II did not differ between torpor and IBE.
These results suggest that the rapid, reversible suppression of mitochondrial
metabolism is due to regulatory changes, perhaps by post-translational
modification during entrance into a torpor bout, and not changes in ETS protein
content.
PMID- 27497597
TI - The Value of a Novel Panel of Cervical Cancer Biomarkers for Triage of HPV
Positive Patients and for Detecting Disease Progression.
AB - In the era of primary vaccination against HPV and at the beginning of the low
prevalence of cervical lesions, introduction of screening methods that can
distinguish between low- and high-grade lesions is necessary in order to maintain
the positive predictive value of screening. This case-control study included 562
women who attended cervical screening or were referred for colposcopy and 140
disease free controls, confirmed by histology and/or cytology. The cases were
stratified by age. Using routine exfoliated liquid based cytological samples RT
PCR measurements of biomarker genes, high-risk HPV testing and liquid based
cytology were performed and used to evaluate different testing protocols
including sets of genes/tests with different test cut-offs for the diagnostic
panels. Three new panels of cellular biomarkers for improved triage of hrHPV
positive women (diagnostic panel) and for prognostic assessment of CIN lesions
were proposed. The diagnostic panel (PIK3AP1, TP63 and DSG3) has the potential to
distinguish cytologically normal hrHPV+ women from hrHPV+ women with CIN2+. The
prognostic gene panels (KRT78, MUC5AC, BPIFB1 and CXCL13, TP63, DSG3) have the
ability to differentiate hrHPV+ CIN1 and carcinoma cases. The diagnostic triage
panel showed good likelihood ratios for all age groups. The panel showed age
unrelated performance and even better diagnostic value under age 30, a unique
feature among the established cervical triage tests. The prognostic gene-panels
demonstrated good discriminatory power and oncogenic, anti-oncogenic grouping of
genes. The study highlights the potential for the gene expression panels to be
used for diagnostic triage and lesion prognostics in cervical cancer screening.
PMID- 27497599
TI - Keeping an Eye on Noisy Movements: On Different Approaches to Perceptual-Motor
Skill Research and Training.
AB - Contemporary theorizing on the complementary nature of perception and action in
expert performance has led to different emphases in the study of movement
coordination and gaze behavior. On the one hand, coordination research has
examined the role of variability in movement control, evidencing that variability
facilitates individualized adaptations during both learning and performance. On
the other hand, and at odds with this principle, the majority of gaze behavior
studies have tended to average data over participants and trials, proposing the
importance of universal 'optimal' gaze patterns in a given task, for all
performers, irrespective of stage of learning. In this article, we discuss new
lines of inquiry with the aim of reconciling these two distinct approaches. We
consider the role of inter- and intra-individual variability in gaze behaviors
and suggest directions for future research.
PMID- 27497600
TI - Explosive Training and Heavy Weight Training are Effective for Improving Running
Economy in Endurance Athletes: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Several strategies have been used to improve running economy (RE).
Defined as the oxygen uptake required at a given submaximal running velocity, it
has been considered a key aerobic parameter related to endurance running
performance. In this context, concurrent strength and endurance training has been
considered an effective method, although conclusions on the optimal concurrent
training cannot yet be drawn. OBJECTIVE: To evaluate the effect of concurrent
training on RE in endurance running athletes and identify the effects of subject
characteristics and concurrent training variables on the magnitude of RE
improvement. METHODS: We conducted a computerized search of the PubMed and Web of
Science databases, and references of original studies were searched for further
relevant studies. The analysis comprised 20 effects in 16 relevant studies
published up to August 2015. The outcomes were calculated as the difference in
percentage change between control and experimental groups (% change) and data
were presented as mean +/- 95 % confidence limit. Meta-analyses were performed
using a random-effects model and, in addition, simple and multiple meta
regression analyses were used to identify effects of age, training status, number
of sessions per week, training duration, type of strength training, and
neuromuscular performance on % change in RE. RESULTS: The concurrent training
program had a small beneficial effect on RE (% change = -3.93 +/- 1.19 %; p <
0.001). In addition, explosive (% change = -4.83 +/- 1.53; p < 0.001) and heavy
weight (% change = -3.65 +/- 2.74; p = 0.009) training programs produced similar
improvements in RE, while isometric training (% change = -2.20 +/- 4.37; p =
0.324) in selected studies did not induce a significant effect. The multiple
linear meta-regression analysis showed that all the differences between % changes
could be explained by including the above-mentioned characteristics of subjects
and weight training program elements. This model showed that the magnitude of the
% change in RE was larger for longer training duration (beta = -0.83 +/- 0.72, p
= 0.02). CONCLUSION: Explosive training and heavy weight training are effective
concurrent training methods aiming to improve RE within a few weeks. However,
long-term training programs seem to be necessary when the largest possible
improvement in RE is desired.
PMID- 27497602
TI - Examining the Washington State Breastfeeding-Friendly Policy Development Process
Using the Advocacy Coalition Framework.
AB - Objectives Breastfeeding promotion is increasingly recognized as a key public
health strategy. Policies can promote breastfeeding by creating supportive
environments and addressing challenges. In 2014, the Washington State legislature
considered bills to create a voluntary recognition system for breastfeeding
friendly hospitals, clinics, worksites and childcare settings. These
Breastfeeding-Friendly Washington (BFW) bills (SB 6298 and HB 2329) did not pass.
Methods The purpose of this case study was to analyze the policy development
process for the BFW bills using the Advocacy Coalition Framework. Data were
collected through semi-structured interviews with key stakeholders in the state
policy process, and document review. We used thematic analysis to identify
deductive and inductive themes. Results Though all policy actors indicated
general support for breastfeeding, two main coalitions (proponents and opponents)
diverged in their support of the BFW bills as policy solutions to address
barriers to breastfeeding. We conducted 29 interviews with mainly bill
proponents, and 54 documents confirmed data about bill opponents. Proponents
supported the bills given increasingly strong evidence of breastfeeding's
benefits and that public policy could address environmental challenges to
breastfeeding. Opponents saw the bills as government overreach into the private
matter of choosing to breastfeed. Opposition to the bills came late in the
session, and proponents felt opponents' messaging misconstrued the intent of the
legislation. Conclusions for Practice Key learnings for developing breastfeeding
friendly state policies include analyzing differences between proponents' and
opponents' beliefs, framing advocacy messages beyond individuals and health,
expanding the coalition outside of traditional health entities, and anticipating
the opposition.
PMID- 27497601
TI - Mechanism of antineoplastic activity of lonidamine.
AB - Lonidamine (LND) was initially introduced as an antispermatogenic agent. It was
later found to have anticancer activity sensitizing tumors to chemo-, radio-, and
photodynamic-therapy and hyperthermia. Although the mechanism of action remained
unclear, LND treatment has been known to target metabolic pathways in cancer
cells. It has been reported to alter the bioenergetics of tumor cells by
inhibiting glycolysis and mitochondrial respiration, while indirect evidence
suggested that it also inhibited l-lactic acid efflux from cells mediated by
members of the proton-linked monocarboxylate transporter (MCT) family and also
pyruvate uptake into the mitochondria by the mitochondrial pyruvate carrier
(MPC). Recent studies have demonstrated that LND potently inhibits MPC activity
in isolated rat liver mitochondria (Ki 2.5MUM) and cooperatively inhibits l
lactate transport by MCT1, MCT2 and MCT4 expressed in Xenopus laevis oocytes with
K0.5 and Hill coefficient values of 36-40MUM and 1.65-1.85, respectively. In rat
heart mitochondria LND inhibited the MPC with similar potency and uncoupled
oxidation of pyruvate was inhibited more effectively (IC50~7MUM) than other
substrates including glutamate (IC50~20MUM). LND inhibits the succinate
ubiquinone reductase activity of respiratory Complex II without fully blocking
succinate dehydrogenase activity. LND also induces cellular reactive oxygen
species through Complex II and has been reported to promote cell death by
suppression of the pentose phosphate pathway, which resulted in inhibition of
NADPH and glutathione generation. We conclude that MPC inhibition is the most
sensitive anti-tumour target for LND, with additional inhibitory effects on MCT
mediated l-lactic acid efflux, Complex II and glutamine/glutamate oxidation.
PMID- 27497603
TI - Changing Practice Patterns and Long-term Outcomes of Endothelial Versus
Penetrating Keratoplasty: A Prospective Dutch Registry Study.
AB - PURPOSE: To compare graft survival, best-corrected visual acuity (BCVA),
endothelial cell density (ECD), and refraction following penetrating keratoplasty
(PK) vs endothelial keratoplasty (EK) for Fuchs endothelial dystrophy (FED) and
pseudophakic bullous keratopathy (PBK). DESIGN: Nonrandomized treatment
comparison with national registry data. METHODS: All consecutive patients
undergoing first keratoplasty for FED and PBK between 1998 and 2014 were
analyzed, with a maximum follow-up of 5 years (mean +/- SD follow-up 39 +/- 20
months, range 0-60 months). Graft survival was analyzed using Kaplan-Meier
survival curves and Cox regression analysis. BCVA, ECD, and refractive error were
compared using linear mixed models. Main outcome measures were graft survival,
BCVA, refraction, and ECD. RESULTS: A total of 5115 keratoplasties (PK = 2390; EK
= 2725) were identified. Two-year graft survival following EK was lower compared
with PK (94.5% vs 96.3%, HR = 1.56, P = .001). Five-year survival was comparable
for EK and PK (93.4% vs 89.7%, HR = 0.89, P = .261). EK graft survival improved
significantly over time while remaining stable for PK. One-year BCVA was better
following EK vs PK (0.34 vs 0.47 logMAR, P < .001). Astigmatism was lower 1 year
after EK vs PK (-1.69 vs -3.52 D, P < .001). One-year ECD was lower after EK vs
PK (1472 vs 1859 cells/mm2, P < .001). At 3 years, ECD did not differ between EK
and PK. CONCLUSIONS: Long-term graft survival after EK and PK is high and
comparable despite lower short-term survival for EK. EK graft survival improved
over time, suggesting a learning curve. EK results in better BCVA, lower
astigmatism, and similar long-term ECD compared with PK for FED and PBK.
PMID- 27497604
TI - Diagnostic performance of a new endoscopic scraper for malignant biliary
strictures: a multicenter prospective study.
AB - BACKGROUND AND AIMS: The efficacy of ERCP for histologic diagnosis of malignant
biliary strictures is disappointingly low. The aim of this study was to
investigate the diagnostic performance of a newly developed endoscopic device
with scraping loops in combination with conventional biopsy forceps. METHODS: We
performed a multicenter single-arm prospective study. Between February 2013 and
December 2014, 123 patients with suspected malignant biliary strictures were
enrolled in the study. The new device and conventional biopsy forceps were
applied for histologic diagnosis by ERCP. The primary outcome was to evaluate
cancer detectability by biopsy forceps, the new device, and their combined use.
RESULTS: Of the 123 patients, 119 were diagnosed with a malignant stricture.
Sufficient samples were collected in 83.7% (103/123), 93.5% (115/123), and 95.9%
(118/123) of patients using biopsy forceps, the new device, and their
combination, respectively. Cancer detectability of forceps biopsy, the new
device, and their combination were 51.3% (61/119), 64.7% (77/119), and 74.8%
(89/119), respectively. The new device had a significantly higher sample yield
and cancer detectability than biopsy forceps (P < .01 and P = .018, respectively,
McNemar test). Complementary use of the new device with biopsy forceps
demonstrated a significantly additive effect in both sample yield and cancer
detection (P < .01 each, McNemar test). The new device detected 48.3% (28/58) of
cancers that were not diagnosed as malignant by biopsy forceps. CONCLUSIONS: The
new endoscopic scraper demonstrated a large sample yield and high cancer
detectability. It could be a first-line tissue-sampling device for biliary
strictures. (University Hospital Medical Information Network Clinical Trial
Registry [UMIN-CTR] (http://www.umin.ac.jp/ctr/index.htm) registration number:
UMIN000009895.).
PMID- 27497605
TI - Reliability and interexaminer agreement for induced tropia test: is normal always
normal?
AB - The purpose of this study was to evaluate the reliability of the fixation
preference testing with 10 and 20 diopter prisms (Delta) in children without
strabismus in order to extrapolate its utility to preverbal children and to
determine interexaminer agreement. Fourty children (24 girls, 16 boys) aged
between 5 and 16 years with normal ophthalmological examination except refractive
errors were included in the study. The visual acuity, refractive errors, and
orthoptic findings were recorded. The base-down prism fixation test was performed
by two experienced examiners with 10Delta and 20Delta. The presence of corrective
movement was recorded as positive result separately for each eye. Best-corrected
visual acuity was 1.0 bilaterally for all patients. All patients had binocular
single vision and stereopsis. First examiner noted bilateral fixation movement in
65 % patients with 10Delta and in 57.5 % with 20Delta, second examiner in 50 %
with 10Delta, and in 37.5 % with 20Delta. Interexaminer agreement was 42.5 % for
10Delta and 54.5 % for 20Delta (p < 0.01). Both examiners observed the fixation
movement to be less frequent in older children. The fixation movement can be
absent or seen asymmetrically even in children with equal visual acuity and
binocular vision. The rate of fixation movement seemed to be reduced with age
possibly due to increased concentration and cooperation of the child. In
addition, there was a remarkable interexaminer variability in both tests. It
should be borne in mind that the findings of prism-guided fixation preference
tests may be misleading in preverbal children.
PMID- 27497607
TI - High-level phylogeny of the Coleoptera inferred with mitochondrial genome
sequences.
AB - The Coleoptera (beetles) exhibits tremendous morphological, ecological, and
behavioral diversity. To better understand the phylogenetics and evolution of
beetles, we sequenced three complete mitogenomes from two families (Cleridae and
Meloidae), which share conserved mitogenomic features with other completely
sequenced beetles. We assessed the influence of six datasets and three inference
methods on topology and nodal support within the Coleoptera. We found that both
Bayesian inference and maximum likelihood with homogeneous-site models were
greatly affected by nucleotide compositional heterogeneity, while the
heterogeneous-site mixture model in PhyloBayes could provide better phylogenetic
signals for the Coleoptera. The amino acid dataset generated more reliable tree
topology at the higher taxonomic levels (i.e. suborders and series), where the
inclusion of rRNA genes and the third positions of protein-coding genes improved
phylogenetic inference at the superfamily level, especially under a heterogeneous
site model. We recovered the suborder relationships as
(Archostemata+Adephaga)+(Myxophaga+Polyphaga). The series relationships within
Polyphaga were recovered as
(Scirtiformia+(Elateriformia+((Bostrichiformia+Scarabaeiformia+Staphyliniformia)+
ucujiformia))). All superfamilies within Cucujiformia were recovered as
monophyletic. We obtained a cucujiform phylogeny of
(Cleroidea+(Coccinelloidea+((Lymexyloidea+Tenebrionoidea)+(Cucujoidea+(Chrysomelo
dea+Curculionoidea))))). This study showed that although tree topologies were
sensitive to data types and inference methods, mitogenomic data could provide
useful information for resolving the Coleoptera phylogeny at various taxonomic
levels by using suitable datasets and heterogeneous-site models.
PMID- 27497606
TI - Ethanol-induced changes in poly (ADP ribose) polymerase and neuronal
developmental gene expression.
AB - Prenatal alcohol exposure has profound effects on neuronal growth and
development. Poly-ADP Ribose Polymerase (PARP) enzymes are perhaps unique in the
field of epigenetics in that they directly participate in histone modifications,
transcription factor modifications, DNA methylation/demethylation and are highly
inducible by ethanol. It was our hypothesis that ethanol would induce PARP
enzymatic activity leading to alterations in neurodevelopmental gene expression.
Mouse E18 cortical neurons were treated with ethanol, PARP inhibitors, and
nuclear hormone receptor transcription factor PPARgamma agonists and antagonists.
Subsequently, we measured PARP activity and changes in Bdnf, OKSM (Oct4, Klf4,
Sox2, c-Myc), DNA methylating/demethylating factors, and Ppargamma mRNA
expression, promoter 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC),
and PPARgamma promoter binding. We found that ethanol reduced Bdnf4, 9a, and Klf4
mRNA expression, and increased c-Myc expression. These changes were reversed with
a PARP inhibitor. In agreement with its role in DNA demethylation PARP inhibition
increased 5MC levels at the c-Myc promoter. In addition, we found that inhibition
of PARP enzymatic activity increased PPARgamma promoter binding, and this
corresponded to increased Bdnf and Klf4 mRNA expression. Our results suggest that
PARP participates in DNA demethylation and reduces PPARgamma promoter binding.
The current study underscores the importance of PARP in ethanol-induced changes
to neurodevelopmental gene expression.
PMID- 27497608
TI - Acupuncture for treating hot flashes in breast cancer patients: an updated meta
analysis.
AB - PURPOSE: The aim of this study was to evaluate the effectiveness of acupuncture
for treatment of hot flash in women with breast cancer. METHODS: The aspects
considered in this study included searching for 12 data bases until April 2015
and consulting reference lists of reviews and related articles. Additional
features studied comprised all articles on human patients with breast cancer
treated with needle acupuncture with or without electrical stimulation for the
treatment of hot flashes. The methodological quality was assessed using the
modified Jadad score. RESULT: The searches identified 12 relevant articles for
inclusion. The meta-analysis without any subgroup or moderator failed to show
favorable effects of acupuncture on reducing the frequency of hot flashes after
intervention (n = 680, SMD = - 0.478, 95 % CI -0.397 to 0.241, P = 0.632) but
exhibited marked heterogeneity of the results (Q value = 83.200, P = 0.000, I^2 =
83.17, tau^2 = 0.310). CONCLUSION: The meta-analysis used had contradictory
results and yielded no convincing evidence to suggest that acupuncture was an
effective treatment of hot flash in patients with breast cancer. Multi-central
studies including large sample size are required to investigate the efficiency of
acupuncture for treating hot flash in patients with breast cancer.
PMID- 27497609
TI - Palmitate-Induced MMP-9 Expression in the Human Monocytic Cells is Mediated
through the TLR4-MyD88 Dependent Mechanism.
AB - BACKGROUND/AIMS: Obese individuals are known to have increased Matrix
metalloproteinase (MMP)-9 plasma levels and MMP-9 is reported to play an
important role in obesity-associated adipose tissue inflammation. Since in
obesity, the levels of circulatory saturated free fatty acid (FFA) palmitate
(palimitic acid) are increased and modulate the expression of inflammatory
mediators, the role of palmitate in the regulation of MMP-9 remains unclear.
METHODS: Human monocytic cell line THP-1 and primary monocytes were stimulated
with palmitate and TNF-alpha (positive control). MMP-9 expression was assessed
with real time RT-PCR and ELISA. Signaling pathways were studied by using THP-1
XBlueTM cells, THP-1-XBlueTM-defMyD cells, anti-TLR4 mAb and TLR4 siRNA.
Phosphorylation of NF-kB and c-Jun was analyzed by Western blotting. RESULTS:
Here, we provide the evidence that palmitate induces MMP-9 expression at both
mRNA (THP-1: 6.8 +/- 1.2 Fold; P = 0.01; Primary monocytes: 5.9 +/- 0.7 Fold; P =
0.0003) and protein (THP1: 1116 +/-14 pg/ml; P<0.001; Primary monocytes: 1426 +/-
13.8; P = 0.0005) levels in human monocytic cells. Palmitate-induced MMP-9
secretion was markedly suppressed by neutralizing anti-TLR-4 antibody (P < 0.05).
Furthermore, genetic silencing of TLR4 by siRNA also significantly abrogated the
palmitate-induced up-regulation of MMP-9. Additionally, MyD88-/- THP-1 cells did
not express MMP-9 in response to palmitate treatment. Increased NF-kappaB/AP-1
activity (P<0.05) was also observed in palmitate-treated THP-1 cells. CONCLUSION:
Altogether, these results show that palmitate induces TLR4-dependent activation
of MMP-9 gene expression, which requires the recruitment of MyD88 leading to
activation of NF-kB/AP-1 transcription factors. Thus, our findings suggest that
the palmitate-induced MMP-9 secretion might be an underlying mechanism of its
increased levels in obesity and related metabolic inflammation.
PMID- 27497610
TI - Reasons for exclusion from intravenous thrombolysis in stroke patients admitted
to the Stroke Unit.
AB - Intravenous (IV) thrombolysis is the treatment in ischemic stroke, but only the
minority of patients receive this medication. The primary objective of this study
was to explore the reasons associated with the decision not to offer IV
thrombolysis to stroke patients admitted to the Stroke Unit (SU). We conducted a
retrospective analysis based on data collected from 876 consecutive stroke
patients admitted to the SU <12 h of symptoms onset, treated or not with IV
thrombolysis at the discretion of the treating neurologist. Of the 876 patients,
449 were thrombolysed and 427 non-thrombolysed. Stroke onset >4.5 h (p = 0.001)
and unknown time of onset (or stroke present on awakening) (p = 0.004) were
reasons listed in the current SPC of Actilyse reasons for exclusion even they
occurred singly, whereas mild deficit (or rapidly improving symptoms) (p <
0.001), extra-cranial conditions with increased risk of bleeding (p = 0.004), and
history of SNC diseases (p = 0.001) only when they occurred in combination.
Severe pre-stroke disability (p = 0.003) was extra-SPC reason for exclusion even
when it occurred singly, whereas early CT hypodensity (p < 0.001) only when it
occurred in combination. After stratification for intra-SPC reasons for
exclusion, early CT hypodensity was associated with decision not offer IV
thrombolysis in patients with mild deficit (p < 0.001), age >80 years (p <
0.001), stroke onset >4.5 h (p = 0.005), and unknown time of onset (p = 0.037),
while severe pre-stroke disability (p = 0.025) and admission under non-stroke
specialist neurologist assessment (p = 0.018) in patients with age >80 years.
There are often unjustified reasons for exclusion from IV thrombolysis in SU.
PMID- 27497612
TI - Formulation of paracetamol-containing pastilles with in situ coating technology.
AB - The focus of this research was to apply the in situ coating technology for
producing paracetamol- (PCT-) containing pastilles for paediatric use from a
eutectic of two sugar alcohols (sorbitol, xylitol) in one step. This type of melt
technology is more cost-efficient and simpler than other conventional tableting
technologies, whereby the formation of the pastilles and their coating occur upon
the same fabrication step. We managed to produce pastilles having a softer core
and a harder, resistant shell in one cooling step. Adding polyethylene glycol
(PEG) 2000 or 6000 to the PCT-containing eutectic, the dissolution rate of PCT
could be considerably increased, especially when using PEG 2000, reaching equal
dissolution characteristics both under mouth- and gastric-specific conditions.
Distributions of the components within the pastilles have been determined by X
ray scattering and Raman spectroscopy. Physico-chemical parameters of the xylitol
sorbitol eutectic and their changes upon adding PCT and PEGs have been
determined, and it has been revealed that xylitol and sorbitol form a new entity
with a distinguished crystal structure. The significant changes in viscosity were
explained and the interaction in the eutectic mixture was investigated using
Fourier transform infrared spectroscopy (FT-IR). The uniformity of the physical
parameters of the pastilles (including size, weight and drug content) also
demonstrates the feasibility of using the cost-efficient and simple one-step
eutectic-cooling technology for manufacturing pastilles.
PMID- 27497611
TI - Retinal sensitivity after selective retina therapy (SRT) on patients with central
serous chorioretinopathy.
AB - PURPOSE: To assess retinal sensitivity after selective retina therapy (SRT) in
patients with central serous chorioretinopathy (CSCR). METHODS: Seventeen eyes of
17 patients with CSCR lasting longer than 3 months were treated with SRT
(wavelength 527 nm Nd: YLF laser, 50-150 MUJ/pulse, spot diameter 200 MUm).
Measurement of best-corrected visual acuity (BCVA), optical coherence tomography,
fluorescence angiography, and microperimetry (MAIATM) were conducted before, and
1 and 3 months after treatment. Microperimetry was performed in the central 10
degrees of the macula, and at the test spots applied near the vascular arcade
for energy titration. In addition to the treatment effect, all test irradiation
spots were thoroughly analyzed with regard to their sensitivity changes. RESULTS:
The mean logMAR BCVA had improved from 0.06 to 0.02 after 1 month (p = 0.11) and
to 0.03 after 3 months (p = 0.003). Eleven out of 17 eyes (64.7%) showed complete
resolution of subretinal fluid after 3 months. Retinal sensitivity in the central
10 degrees increased after 1 month (median: 25.9 dB) and 3 months (26.6 dB) as
compared with that before treatment (23.0 dB) (p < 0.001). Analysis of the test
spots revealed a slight decrease in retinal sensitivity after 1 month (DeltadB =
0.5 +/- 2.1, p = 0.006), while there was no significant difference from baseline
after 3 months (DeltadB = -0.3 +/- 2.2, p = 0.09). No correlation was found
between laser energy and the change in focal retinal sensitivity. CONCLUSIONS:
Results suggest that SRT is a safe and effective treatment for persistent CSCR
and does not leave permanent scotoma regardless of irradiation energy in the
therapeutic range.
PMID- 27497613
TI - Conversion of sustained release omeprazole loaded buccal films into fast
dissolving strips using supercritical carbon dioxide (scCO2) processing, for
potential paediatric drug delivery.
AB - This study involves the development of thin oral solvent cast films for the
potential delivery of the proton pump inhibitor, omeprazole (OME) via the buccal
mucosa for paediatric patients. OME containing films were prepared from ethanolic
gels (1% w/w) of metolose (MET) with polyethylene glycol (PEG 400) (0.5% w/w) as
plasticiser, and L-arginine (l-arg) (0.2% w/w) as a stabilizer and dried in an
oven at 40 degrees C. The blank and drug loaded films were divided into two
groups, one group was subjected to supercritical carbon dioxide (scCO2) treatment
and the other group untreated. The untreated and scCO2 treated films were then
characterised using differential scanning calorimetry, thermogravimetric
analysis, scanning electron microscopy, X-ray diffraction, Fourier transform
infrared spectroscopy, hydration (swelling), mucoadhesion and in vitro drug
dissolution studies. Treatment of the solvent cast films with scCO2 caused
significant changes to the functional and physical properties of the MET films.
The original drug loaded MET films showed a sustained release of OME (1h),
whereas scCO2 treatment of the formulations resulted in fast dissolving films
with >90% drug release within 15min.
PMID- 27497614
TI - Dosing errors in preterm neonates due to flow rate variability in multi-infusion
syringe pump setups: An in vitro spectrophotometry study.
AB - BACKGROUND: Drug administration on the neonatal intensive care unit is often
associated with adverse events. This may be due to dosing errors caused by multi
infusion setups. We aim to investigate these dosing errors. MATERIAL AND METHODS:
N=3 experiment using a medication schedule, multi-infusion setup (three pumps)
and disposables as applied on the NICU. In-line and real-time absorption
spectrophotometry was used with dyes as substitutes for pharmaceuticals. Three
flow rate changes lasting 1h were initiated. Subsequently, the possible dosing
errors were estimated in the parallel pumps. In addition, startup durations, the
times the flow rates required to reach steady state after significant dosing
errors, as well as the total dosing error were measured. RESULTS: Contribution of
the start-up delays to the cumulative dosing errors was the largest. However,
initiated flow rate changes resulted in significant dosing errors in the parallel
pumps as well. The total dosing error was not significant. The significant peak
errors were between 48.2% and -32.5% at flow rate increase and decrease,
respectively. Startup delays of up to 42.6min were measured. CONCLUSIONS:
Applying multi-infusion while following a neonatal medication schedule may
temporarily result in dosing errors, which can be relevant for fast-acting
medications. Awareness may mitigate the risks.
PMID- 27497615
TI - Antibiotic resistance and virulence genes in coliform water isolates.
AB - Widespread fecal pollution of surface water may present a major health risk and a
significant pathway for dissemination of antibiotic resistance bacteria. The
River Rhine is one of the longest and most important rivers in Europe and an
important raw water source for drinking water production. A total of 100 coliform
isolates obtained from River Rhine (Germany) were examined for their
susceptibility to seven antimicrobial agents. Resistances against amoxicillin,
trimethoprim/sulfamethoxazole and tetracycline were detected in 48%, 11% and 9%
of isolates respectively. The antibiotic resistance could be traced back to the
resistance genes blaTEM, blaSHV, ampC, sul1, sul2, dfrA1, tet(A) and tet(B).
Whereby, the ampC gene represents a special case, because its presence is not
inevitably linked to a phenotypic antibiotic resistance. Multiple antibiotics
resistance was often accompanied by the occurrence of class 1 or 2 integrons. E.
coli isolates belonging to phylogenetic groups A and B1 (commensal) were more
predominant (57%) compared to B2 and D groups (43%) which are known to carry
virulent genes. Additionally, six E. coli virulence genes were also detected.
However, the prevalence of virulence genes in the E. coli isolates was low (not
exceeding 4.3% per gene) and no diarrheagenic E. coli pathotypes were detected.
This study demonstrates that surface water is an important reservoir of ARGs for
a number of antibiotic classes such as sulfonamide, trimethoprim, beta-lactam
antibiotics and tetracycline. The occurrence of antibiotic resistance in coliform
bacteria isolated from River Rhine provides evidence for the need to develop
management strategies to limit the spread of antibiotic resistant bacteria in
aquatic environment.
PMID- 27497616
TI - Modeling protein-DNA binding via high-throughput in vitro technologies.
AB - Protein-DNA binding plays a central role in gene regulation and by that in all
processes in the living cell. Novel experimental and computational approaches
facilitate better understanding of protein-DNA binding preferences via high
throughput measurement of protein binding to a large number of DNA sequences and
inference of binding models from them. Here we review the state of the art in
measuring protein-DNA binding in vitro, emphasizing the advantages and
limitations of different technologies. In addition, we describe models for
representing protein-DNA binding preferences and key computational approaches to
learn those from high-throughput data. Using large experimental data sets, we
test the performance of different models based on different measuring techniques.
We conclude with pertinent open problems.
PMID- 27497617
TI - Overexpression of microRNA-155 suppresses chemokine expression induced by
Interleukin-13 in BEAS-2B human bronchial epithelial cells.
AB - BACKGROUND: MicroRNAs are non-coding small RNAs that regulate expression of
target genes by binding to 3' untranslated regions. In this study, we used
bronchial epithelial cells to investigate in vitro the role of the microRNA miR
155 in the expression of chemokines associated with airway inflammation. miR-155
has previously been reported to regulate allergic inflammation. METHODS: BEAS-2B
bronchial epithelial cells were cultured and transfected with mimic or inhibitor
oligonucleotides to overexpress or downregulate miR-155, as confirmed by real
time PCR. Cells were then stimulated with tumor necrosis factor-alpha,
interleukin-13 (IL-13), and a double stranded RNA that binds Toll-like receptor
3. Expression and secretion of the chemokines CCL5, CCL11, CCL26, CXCL8, and
CXCL10 were then quantified by real-time PCR and ELISA, respectively.
Phosphorylation of signal transducer and activator of transcription 6 (STAT6), a
target of the IL-13 receptor, was analyzed by ELISA. RESULTS: miR-155
overexpression significantly suppressed IL-13-induced secretion of CCL11 and
CCL26. These effects were specific, and were not observed for other chemokines,
nor in cells with downregulated miR-155. miR-155 overexpression also suppressed
CCL11 and CCL26 mRNA, but did not affect expression of the IL-13 receptor or
phosphorylation of STAT6. CONCLUSIONS: miR-155 specifically inhibits IL-13
induced expression of eosinophilic chemokines CCL11 and CCL26 in bronchial
epithelial cells, even though the 3'-untranslated region of these genes do not
contain a consensus binding site for miR-155.
PMID- 27497618
TI - Serum TARC levels are strongly correlated with blood eosinophil count in patients
with drug eruptions.
AB - BACKGROUND: This study aims to evaluate the relationship between serum thymus and
activation-regulated chemokine (TARC) levels with various clinicopathological
conditions in patients with drug eruptions. The value of TARC in diagnosing drug
induced hypersensitivity syndrome (DIHS) was also examined. METHODS: Study
participants included 84 patients who presented with generalized eruptions
suspected to be drug-related, including DIHS, Stevens-Johnson syndrome
(SJS)/toxic epidermal necrolysis (TEN), maculopapular exanthema (MPE), erythema
multiforme (EM), erythroderma, and toxicoderma. The correlation coefficients
between serum TARC levels and clinical parameters in peripheral blood samples
were calculated. RESULTS: Serum TARC levels in patients with DIHS were higher
than those found in patients with SJS/TEN, MPE, EM, and toxicoderma. TARC levels
had 100% sensitivity and 92.3% specificity in diagnosing DIHS, with a threshold
value of 13,900 pg/mL. Serum TARC levels positively correlated with age, white
blood cell (WBC) count, neutrophil count, eosinophil count, monocyte count,
atypical lymphocyte (Aty-ly) count, serum blood urea nitrogen (BUN) levels, and
creatinine (Cr) levels. It negatively correlated with serum total protein (TP),
albumin (Alb), and estimated glomerular filtration rate (eGFR). Among these
clinical parameters, blood eosinophil counts were most strongly correlated with
serum TARC levels, with a correlation coefficient of 0.53. CONCLUSIONS: Serum
TARC levels are well correlated with blood eosinophil counts in patients with
generalized drug eruptions, indicating that Th2-type immune reactions underlie
TARC production. Serum TARC measurements also have potent diagnostic value for
DIHS, with high sensitivity and specificity.
PMID- 27497619
TI - Perinatal Palliative Care.
PMID- 27497620
TI - The Ep152R ORF of African swine fever virus strain Georgia encodes for an
essential gene that interacts with host protein BAG6.
AB - African swine fever virus (ASFV) is the etiological agent of a contagious and
often lethal disease of domestic pigs that has significant economic consequences
for the swine industry. The viral genome encodes for more than 150 genes, and
only a select few of these genes have been studied in some detail. Here we report
the characterization of open reading frame Ep152R that has a predicted complement
control module/SCR domain. This domain is found in Vaccinia virus proteins that
are involved in blocking the immune response during viral infection. A
recombinant ASFV harboring a HA tagged version of the Ep152R protein was
developed (ASFV-G-Ep152R-HA) and used to demonstrate that Ep152R is an early
virus protein. Attempts to construct recombinant viruses having a deleted Ep152R
gene were consistently unsuccessful indicating that Ep152R is an essential gene.
Interestingly, analysis of host-protein interactions for Ep152R using a yeast two
hybrid screen, identified BAG6, a protein previously identified as being required
for ASFV replication. Furthermore, fluorescent microscopy analysis confirms that
Ep152R-BAG6 interaction actually occurs in cells infected with ASFV.
PMID- 27497621
TI - Immunogenicity and protective efficacy of recombinant fusion proteins containing
spike protein of infectious bronchitis virus and hemagglutinin of H3N2 influenza
virus in chickens.
AB - Infectious bronchitis (IB) is an acute and highly contagious viral respiratory
disease of chickens and vaccination is the main method for disease control. The
S1 protein, which contains several virus neutralization epitopes, is considered
to be a target site of vaccine development. However, although protective immune
responses could be induced by recombinant S1 protein, the protection rate in
chickens was still low (<50%). Here, we generated fused S1 proteins with HA2
protein (rS1-HA2) or transmembrane domain and cytoplasmic tail (rS1-H3(TM)) from
hemagglutinin of H3N2 influenza virus. After immunization, animals vaccinated
with fusion proteins rS1-HA2 and rS1-H3(TM) demonstrated stronger robust humoral
and cellular immune responses than that of rS1 and inactivated M41 vaccine. The
protection rates of groups immunized with rS1-HA2 (87%) were significantly higher
than the groups inoculated with rS1 (47%) and inactivated M41 vaccine (53%). And
chickens injected with rS1-H3(TM) had similar level of protection (73%) comparing
to chickens vaccinated with rS1 (47%) (P=0.07). Our data suggest that S1 protein
fused to the HA2 or TM proteins from hemagglutinin of H3N2 influenza virus may
provide a new strategy for high efficacy recombinant vaccine development against
IBV.
PMID- 27497622
TI - A collaborative study of an alternative in vitro potency assay for the Japanese
encephalitis vaccine.
AB - The use of inactivated Japanese encephalitis (JE) vaccines has been ongoing in
East Asia for 40 years. A mouse immunogenicity assay followed by a Plaque
Reduction Neutralization (PRN) Test (PRNTest) is currently recommended for each
lot release of the vaccine by many national authorities. We developed an
alternative in vitro ELISA to determine the E antigen content of the Japanese
encephalitis virus to observe the 3Rs strategy. A collaborative study for
replacing the in vivo potency assay for the Japanese encephalitis vaccine with
the in vitro ELISA assay was confirmed comparability between these two methods.
The study demonstrated that an in vitro assay could perform faster and was more
convenient than the established in vivo PRNTest. Moreover, this assay had better
precision and reproducibility compared with the conventional in vivo assay.
Additionally, the content of antigen determined using the in vitro ELISA
correlated well with the potency of the in vivo assay. Furthermore, this method
allowed discrimination between individual lots. Thus, we propose a progressive
switch from the in vivo assay to the in vitro ELISA for JE vaccine quality
control.
PMID- 27497623
TI - Association of Universal Bilirubin Screening With Socioeconomic Disparities in
Newborn Follow-up.
AB - OBJECTIVE: To determine whether implementation of universal bilirubin screening
in Ontario, Canada is associated with improved rates of recommended follow-up
care across socioeconomic status (SES). METHODS: We conducted a retrospective
population-based cohort study of all babies born at >=35 weeks' gestation and
discharged to home within 72 hours from 97 hospitals between April, 2003 and
February, 2011. We used linked administrative health data sets to measure
recommended follow-up care (physician visit within 1 day of discharge for babies
discharged <=24 hours after birth, or physician visit within 2 days for babies
discharged 24-72 hours after birth). We used maternal postal code and the
Canadian Deprivation Index to determine material deprivation quintile. We modeled
the relationship between universal bilirubin screening and outcomes using
generalized estimating equations to account for clustering according to hospital,
underlying temporal trends, and important covariates. RESULTS: Universal
bilirubin screening was associated with a modest increase in recommended follow
up from 29.9% to 35.0% (n = 711,242; adjusted relative risk: 1.11; P = .047).
Disparity in recommended follow-up increased after screening implementation, with
40% of the crude increase attributable to the highest SES quintile and none to
the lowest SES quintile. CONCLUSIONS: Universal bilirubin screening has had only
a modest effect in ensuring timely follow-up for Ontario newborn babies, which
represents an ongoing weakness in efforts to prevent severe hyperbilirubinemia.
The observed increase in SES disparity in access to recommended follow-up
suggests that universal programs that fail to address root causes of disparities
might lead to overall improvements in population outcomes but increased inequity.
PMID- 27497624
TI - Pediatric Neurosurgical Outcomes Following a Neurosurgery Health System
Intervention at Mulago National Referral Hospital in Uganda.
AB - OBJECTIVE: Pediatric neurosurgical cases have been identified as an important
target for impacting health disparities in Uganda, with over 50% of the
population being less than 15 years of age. The objective of the present study
was to evaluate the effects of the Duke-Mulago collaboration on pediatric
neurosurgical outcomes in Mulago National Referral Hospital. METHODS: We
performed retrospective analysis of all pediatric neurosurgical cases who
presented at Mulago National Referral Hospital in Kampala, Uganda, to examine
overall, preprogram (2005-2007), and postprogram (2008-2013) outcomes. We
analyzed mortality, presurgical infections, postsurgical infections, length of
stay, types of procedures, and significant predictors of mortality. Data on
neurosurgical cases was collected from surgical logbooks, patient charts, and
Mulago National Referral Hospital's yearly death registry. RESULTS: Of 820
pediatric neurosurgical cases, outcome data were complete for 374 children. Among
children who died within 30 days of a surgical procedure, the largest group was
less than a year old (45%). Postinitiation of the Duke-Mulago collaboration, we
identified an overall increase in procedures, with the greatest increase in cases
with complex diagnoses. Although children ages 6-18 years of age were 6.66 times
more likely to die than their younger counterparts preprogram, age was no longer
a predictive variable postprogram. When comparing pre- and postprogram outcomes,
mortality among pediatric patients within 30 days after a neurosurgical procedure
increased from 4.3% to 10.0%, mortality after 30 days increased slightly from
4.9% to 5.0%, presurgical infections decreased by 4.6%, and postsurgery
infections decreased slightly by 0.7%. CONCLUSIONS: Our data show the provision
of more complex neurological procedures does not necessitate improved outcomes.
Rather, combining these higher-level procedures with essential pre- and
postoperative care and continued efforts in health system strengthening for
pediatric neurosurgical care throughout Uganda will help to address and decrease
the burden throughout the country.
PMID- 27497625
TI - Rapid simulated gastric fluid digestion of in-seed/grain proteins expressed in
genetically engineered crops.
AB - The speed of simulated gastric digestion of proteins expressed in genetically
engineered (GE) crops is commonly used to inform the allergenicity risk
assessment. However, persistence of purified proteins in simulated gastric fluid
(SGF) is poorly correlated with the allergenic status of proteins. It has been
proposed that the plant or food matrix may affect the digestion of proteins and
should be considered in interpreting digestion results. Here the SGF digestion of
several GE proteins both as purified preparations and in soybean, corn, and
cotton seed/grain extracts (in-matrix) are compared. Cry1F, Cry1Ac,
phosphinothricin acetyltransferase (PAT), aryloxyalkanoate dioxygenase-1 (AAD-1),
aryloxyalkanoate dioxygenase-12 (AAD-12), and double mutant 5-enol
pyruvylshikimate-3-phosphate synthase (2mEPSPS) were all found to rapidly digest
both as purified protein preparations and in seed/grain extracts from GE crops
expressing these proteins. Based on these results, purified protein from
microbial sources is a suitable surrogate for proteins in-matrix when conducting
SGF digestion studies.
PMID- 27497626
TI - Long-term successional dynamics of microbial association networks in anaerobic
digestion processes.
AB - It is of great interest to elucidate underlying mechanisms to maintain stability
of anaerobic digestion, an important process in waste treatment. By operating
triplicate anaerobic digesters continuously for two years, we found that
microbial community composition shifted over time despite stable process
performance. Using an association network analysis to evaluate microbial
interactions, we detected a clear successional pattern, which exhibited
increasing modularity but decreasing connectivity among microbial populations.
Phylogenetic diversity was the most important factor associated with network
topology, showing positive correlations with modularity but negative correlations
with network complexity, suggesting induced niche differentiation over time.
Positive, but not negative, correlation strength was significantly related (p <
0.05) to phylogeny. Furthermore, among populations exhibiting consistent positive
correlations across networks, close phylogenetic linkages were evident (e.g.
Clostridiales organisms). Clostridiales organisms were also identified as
keystone populations in the networks (i.e., they had large effects on other
species), suggestive of an important role in maintaining process stability. We
conclude that microbial interaction dynamics of anaerobic digesters evolves over
time during stable process performance.
PMID- 27497627
TI - Comparative analysis of the photocatalytic reduction of drinking water oxoanions
using titanium dioxide.
AB - Regulated oxidized pollutants in drinking water can have significant health
effects, resulting in the need for ancillary treatment processes. Oxoanions
(e.g., nitrate) are one important class of oxidized inorganic ions. Ion exchange
and reverse osmosis are often used treatment processes for oxoanions, but these
separation processes leave behind a concentrated waste product that still
requires treatment or disposal. Photocatalysis has emerged as a sustainable
treatment technology capable of catalytically reducing oxoanions directly to
innocuous byproducts. Compared with the large volume of knowledge available for
photocatalytic oxidation, very little knowledge exists regarding photocatalytic
reduction of oxoanion pollutants. This study investigates the reduction of
various oxoanions of concern in drinking water (nitrate, nitrite, bromate,
perchlorate, chlorate, chlorite, chromate) using a commercial titanium dioxide
photocatalyst and a polychromatic light source. Results showed that oxoanions
were readily reduced under acidic conditions in the presence of formate, which
served as a hole scavenger, with the first-order rate decreasing as follows:
bromate > nitrite > chlorate > nitrate > dichromate > perchlorate, corresponding
to rate constants of 0.33, 0.080, 0.052, 0.0074, 0.0041, and 0 cm2/photons *
1018, respectively. Only bromate and nitrite were reduced at neutral pH, with
substantially lower rate constants of 0.034 and 0.0021 cm2/photons * 1018,
respectively. No direct relationship between oxoanion physicochemical properties,
including electronegativity of central atom, internal bond strength, and
polarizability was discovered. However, observations presented herein suggest the
presence of kinetic barriers unique to each oxoanion and provides a framework for
investigating photocatalytic reduction mechanisms of oxoanions in order to design
better photocatalysts and optimize treatment.
PMID- 27497629
TI - Head and neck lymphatic malformation and treatment: Clinical study of 23 cases.
AB - OBJECTIVES: Head and neck lymphatic malformation is a rare benign tumor, mainly
affecting children under 1 year of age. Total resection is often difficult, and
recurrence is frequent. Functional and esthetic sequelae are a major issue.
MATERIALS AND METHODS: A single-center retrospective study recruited patients
with head and neck lymphatic malformation managed surgically, with or without
associated sclerosis by alcohol, bleomycin or aetoxisclerol, between January 1,
2004 and December 31, 2013. Local control, recurrence and complications rates
were analyzed, as were swallowing disorder, tracheostomy and impaired phonation.
RESULTS: Twenty-three patients, with a mean age of 15.80 years, were included.
Location was suprahyoid in 17 cases (73.91%) and infrahyoid in 6 (26.09%). There
were 11 macrocysts (47.82%), 2 microcysts (8.70%) and 10 mixed lesions (43.48%).
Three patients showed spontaneous resolution; 12 patients (52.17%) underwent a
single surgical procedure, 2 (8.7%) multiple procedures, 2 (8.7%) 1 surgical
procedure and 1 sclerosis, 2 (8.7%) 1 surgical procedure and multiple scleroses,
and 2 (8.7%) multiple procedures and multiple scleroses. The local control rate
was 69.56%. There were 8 recurrences (34.78%), all in suprahyoid microcystic or
mixed lesions. There were 2 complications (8.7%): 1 severe upper cervical edema
following sclerosis of the floor of the mouth, and 1 postsurgical palsy of the
marginal mandibular branch of the facial nerve. In 1 case (4.35%), a nasogastric
tube was required for 6 days, without tracheostomy. CONCLUSION: Recurrence was
frequent, with non-negligible functional and esthetic impact, especially in case
of suprahyoid and microcystic lesion.
PMID- 27497628
TI - Prognosis of Good syndrome: mortality and morbidity of thymoma associated
immunodeficiency in perspective.
AB - Good syndrome (GS) or thymoma-associated immunodeficiency, is a rare condition
that has only been studied in retrospective case series. General consensus was
that GS has a worse prognosis than other humoral immunodeficiencies. In this
study, physicians of GS patients completed two questionnaires with a two year
interval with data on 47 patients, 499 patient years in total. Results on
epidemiology, disease characteristics, and outcome are presented. Mean age at
diagnosis was 60years and median follow-up from onset of symptoms was 9years.
There was a high frequency of respiratory tract infections due to encapsulated
bacteria. Median survival was 14years. Survival was reduced compared to age
matched population controls (5-year survival: 82% versus 95%, p=0.008). In this
cohort survival was not associated with gender (HR 0.9, 95% CI 0.3-3.0),
autoimmune diseases (HR 2.9, 95% CI 0.8-10.1) or immunosuppressive use (HR 0.3,
95% CI: 0.1-1.2).
PMID- 27497630
TI - Genetic characterization of Shiga toxin-producing Escherichia coli (STEC) and
atypical enteropathogenic Escherichia coli (EPEC) isolates from goat's milk and
goat farm environment.
AB - The aim of this study was to characterize a collection of 44 Shiga toxin
producing (STEC) and enteropathogenic Escherichia coli (EPEC) isolated from goat
milk and goat farm environment. Of the 19 STEC isolates, five (26.3%) carried the
stx1 gene, four (21.1%) the stx2 gene and 10 (52.6%) presented both stx genes.
Six (31.6%) STEC strains were eae-positive and belonged to serotypes related to
severe human disease (O157:H7 and O5:HNM). Another seven STEC strains were of
serotype O146:H21 and three of serotype O166:H28, also linked to human disease.
The STEC strains isolated from goat milk were of serotypes potentially pathogenic
for humans. All the 25 EPEC isolates were considered atypical (aEPEC) and one
aEPEC strain was of serotype O26:H11, a serotype frequently isolated in children
with diarrhea. Multilocus sequence typing (MLST) was carried out with seven
housekeeping genes and 23 sequence types (ST) were detected, 14 of them newly
described. Twelve STs grouped STEC isolates and 11 STs grouped EPEC isolates.
Genetic typing by pulsed field gel electrophoresis (PFGE) resulted in 38 patterns
which grouped in 10 clusters. Well-defined groups were also observed for strains
of pathogenic serotypes. In conclusion, strains of STEC and aEPEC belonging to
serotypes related to severe human disease have been detected in goat milk and the
goat farm environment. Ruminants are an important reservoir of STEC strains and
the role of these animals as carriers of other pathogenic types of E. coli seems
to be an emerging concern.
PMID- 27497631
TI - Co-administration of succinylated gelatine with a (99m)Tc-bombesin analogue,
effects on pharmacokinetics and tumor uptake.
AB - The bombesin analogue, [(99m)Tc-GGC]-(Ornithine)3-BN(2-14), (99m)Tc-BN-O,
targeting gastrin releasing peptide receptors (GRPrs) on the surface of tumors,
was pre-clinically investigated as potential imaging agent for single photon
emission computed tomography (SPECT). In addition, the improvement of its
pharmacokinetic profile (PK) was investigated through the co-administration of a
succinylated gelatin plasma expander (Gelofusine), aiming to reduce its kidney
accumulation and enhance its tumor-to-normal tissue contrast ratios.
Biodistribution data were collected from normal mice and rats, and PC-3 tumor
bearing mice, in reference to its PK, metabolism and tumor uptake. Imaging data
were also collected from PC-3 tumor bearing mice. Biodistribution and imaging
experiments showed that (99m)Tc-BN-O was able to efficiently localize the tumor
(5.23 and 7.00% ID/g at 30 and 60min post injection, respectively), while at the
same time it was rapidly cleared from the circulation through the kidneys. HPLC
analysis of kidney samples, collected at 60min p.i. from normal mice and rats,
showed that the majority of radioactivity detected was due to intact peptide i.e.
56% for mice and 73% for rats. Co-administration of (99m)Tc-BN-O with Gelo
resulted in the reduction of kidney uptake in both animal models. The integrated
area under the curve (AUC30-60 min) from the concentration-time plots of kidneys
was decreased in both mice and rats by 25 and 50%, respectively. In PC-3 tumor
bearing mice, an increase of tumor uptake (AUCtumor increased by 69%) was also
observed with Gelo. An improvement in tumor-to-blood and tumor-to-normal tissue
ratios was noted in all cases with the exception of the pancreas, which normally
expresses GRPr. The results of this preclinical study may also be extended to
other similar peptides, which are utilized in prostate cancer imaging and present
similar PK profile.
PMID- 27497634
TI - Protection from diclofenac-induced liver injury by Yulangsan polysaccharide in a
mouse model.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Millettia pulchra Kurz var-laxior (Dunn) Z. Wei,
a wild-growing plant of the family Fabaceae is known to possess multifarious
medicinal properties. Yulangsan polysaccharide (YLSPS) is a chief ingredient of
its root, which has been used in Chinese traditional medicine with a long history
for remedy of acute or chronic hepatitis and jaundice. AIM OF THE STUDY: To
investigate the ability of the YLSPS to protect against diclofenac-induced
hepatotoxicity in mice. MATERIALS AND METHODS: Mice were orally treated with
YLSPS daily 1h after the injection of diclofenac for 2 weeks. Dimethyl diphenyl
bicarboxylate was used as a reference drug. RESULTS: YLSPS effectively reduced
the elevated levels of serum alanine aminotransferase, aspartate
aminotransferase, and alkaline phosphatase and enhanced the reduction of
superoxide dismutase, catalase, and glutathione peroxidase activities in the
liver. Moreover, the content of malondialdehyde was reduced by treatment with
YLSPS, and histological findings also confirmed the anti-hepatotoxic activity. In
addition, YLSPS significantly inhibited proinflammatory mediators, such as tumor
necrosis factor-alpha and interleukin 1 beta. YLSPS also enhanced mitochondrial
antioxidants and inhibited cell death by preventing the down-regulation of Bcl-2
and the up-regulation and release of Bax along with caspase 9 and 3 activity;
thus, these findings confirm the involvement of mitochondria in diclofenac
induced apoptosis. CONCLUSION: The results indicate that protective effects of
YLSPS against diclofenac-induced acute hepatic injury may rely on its effect on
reducing oxidative stress, suppressing inflammatory responses, and improving drug
metabolizing enzyme activity in the liver.
PMID- 27497632
TI - Paradoxical effects of Auger electron-emitting (111)In-DTPA-NLS-CSL360
radioimmunoconjugates on hCD45(+) cells in the bone marrow and spleen of leukemia
engrafted NOD/SCID or NRG mice.
AB - INTRODUCTION: (111)In-DTPA-NLS-CSL360 radioimmunoconjugates (RIC) recognize the
overexpression of the interleukin-3 receptor alpha-subchain (CD123) relative to
the beta-subchain (CD131) on leukemia stem cells (LSC). Our aim was to study
Auger electron radioimmunotherapy (RIT) of acute myeloid leukemia (AML) with
(111)In-DTPA-NLS-CSL360 in non-obese diabetic severe combined immunodeficiency
(NOD/SCID) mice or NOD-Rag1(null)IL2rgamma(null) (NRG) mice engrafted with
CD123(+) human AML-5 cells. METHODS: The toxicity of three doses of (111)In-DTPA
NLS-CSL360 (3.3-4.8MBq; 11-15MUg each) injected i.v. every two weeks was studied
in non-engrafted NOD/SCID or NRG mice pre-treated with 200cGy of gamma-radiation
required for AML engraftment. Engraftment efficiency of (1-5)*10(6) cells AML-5
cells inoculated i.v. into NOD/SCID or NRG mice was assessed by flow cytometric
analysis for human CD45(+) (hCD45(+)) cells in the bone marrow (BM) and spleen.
AML-5 engrafted mice were treated with two or three doses (3.7MBq; 10MUg each)
every two weeks of (111)In-DTPA-NLS-CSL360, non-specific (111)In-DTPA-NLS-hIgG,
unlabeled CSL360 (10MUg) or normal saline. The percentage of hCD45(+) cells in
the BM and spleen were measured at one week after completion of treatment.
RESULTS: (111)In-DTPA-NLS-CSL360 in combination with 200cGy of gamma-radiation
caused an initial transient decrease in body weight in NOD/SCID but not in NRG
mice. There were no hematological, liver or kidney toxicities. The spleen
exhibited 13-fold lower engraftment efficiency than the BM in NOD/SCID mice
inoculated with 1*10(6) cells but both organs were highly (>85%) engrafted in NRG
mice. Unexpectedly, (111)In-DTPA-NLS-CSL360 or non-specific (111)In-DTPA-NLS-hIgG
caused a paradoxical 1.5-fold increase (P<0.0001) in the proportion of hCD45(+)
cells in the BM of NOD/SCID mice compared to normal saline treated mice. (111)In
DTPA-NLS-CSL360 reduced hCD45(+) cells in the spleen by 3.0-fold compared to
(111)In-DTPA-NLS-hIgG (P=0.0015) but the proportion of hCD45(+) cells was not
significantly different than in normal saline treated mice. Unlabeled CSL360
decreased the percentage of hCD45(+) cells in the BM (P=0.004) or spleen
(P=0.007) in NOD/SCID mice by 1.6-fold and 2.5-fold, respectively. (111)In-DTPA
NLS-CSL360 or unlabeled CSL360 did not decrease the proportion of hCD45(+) cells
in the BM or spleen of NRG mice, due to a much higher leukemic burden.
CONCLUSION: (111)In-DTPA-NLS-CSL360 and (111)In-DTPA-NLS-hIgG caused a
paradoxical increase in the proportion of hCD45(+) cells in the BM of NOD/SCID
mice. This may be due to a priming effect on the BM niche that promotes expansion
of engrafted hCD45(+) cells, analogous to gamma-radiation required for AML
engraftment. There appears to be a competition between this effect and the
cytotoxic effects of the Auger electrons on leukemia cells. The effectiveness of
(111)In-DTPA-NLS-CSL360 on reducing hCD45(+) cells in the BM or spleen of
NOD/SCID and NRG mice was dependent on the leukemic burden. ADVANCES IN KNOWLEDGE
AND IMPLICATIONS FOR PATIENT CARE: This study demonstrates for the first time a
paradoxical radiation priming effect of RIT on enhancing the hCD45(+) cell
population in the BM and spleen of NOD/SCID or NRG mice. Our results have
important implications for preclinical evaluation of radioimmunotherapies for
patients with AML.
PMID- 27497633
TI - Neuroprotective effects of melatonin as evidenced by abrogation of oxaliplatin
induced behavioral alterations, mitochondrial dysfunction and neurotoxicity in
rat brain.
AB - Neurotoxicity is a burdensome consequence of platinum-based chemotherapy that
neutralizes the administration of effective dosage and often prompts treatment
withdrawal. Oxaliplatin (Oxa), a third-era platinum analogue that is active
against both early-organize and progressed colorectal growth, produces critical
neurotoxicity. It has been reported that the Melatonin (Mel) is a pineal hormone
its metabolites display important antioxidant properties in nervous system. There
is dearth of literature involving the role of mitochondria and cytosolic
compartments mediated Oxa-induced neurotoxicity and its underlying mechanisms are
still debatable. Rats were pre-treated with Mel (10mg/kg b.wt., i.p.) and treated
with Oxa (4mg/kg b.wt. i.p.) for 5 consecutive days. For neurobehavioral
performances, decreased locomotor activity and muscular strength were observed in
rats. Treatment with Mel in Oxa treated rats could protect the Oxa induced
alterations in motor activity and muscular strength. For painful neuropathy,
thermal hyperalgesia/nociceptive tests were evaluated. In addition, pre-treatment
of Mel could block or alter the inactivation of Bcl-2, caspase 3 apoptotic
protein and alterations Cytochrome c (Cyt c) release in an Oxa rich environment.
Pre-treatment of Mel have shown an alteration in hyperalgesia behaviour in Oxa
treated rats. Oxidative stress biomarkers, levels of non-enzymatic antioxidants
and mitochondrial complexes were evaluated against neurotoxicity induced by Oxa.
Mel pre-treatment replenished the mitochondrial lipid peroxidation levels and
protein carbonyl content induced by Oxa. Mel also modulated altered non
enzymatic, enzymatic antioxidants and complex enzymes of mitochondria. Futures
studies are also required to identify other molecular markers involved in
neurotoxicity induced by Oxa and possible action of Mel in its modulation.
PMID- 27497635
TI - The effects of Chuanxiong on the pharmacokinetics of warfarin in rats after
biliary drainage.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong Rhizoma (rhizomes of Ligusticum
chuanxiong Hort), known as Chuanxiong in Chinese, has been used for treating
cardiovascular diseases for centuries. Chuanxiong is a classical activating blood
circulation herb in the treatment of thromboembolism heart diseases. Warfarin
often combines with herbal prescriptions containing Chuanxiong in China. AIM OF
THE STUDY: The herb-drug interaction involving enterohepatic circulation process
remains unclear. This study aimed to elucidate the effects of Chuanxiong Rhizoma
on the pharmacokinetics of warfarin in rats after biliary drainage. MATERIALS AND
METHODS: Thirty-two rats were randomly divided into four groups: WN (healthy rats
after the gastric-administration of 0.5mg/kg warfarin sodium), WO (a rat model of
biliary drainage after the gastric-administration of 0.5mg/kg warfarin sodium),
WCN (healthy rats after the gastric-administration of 0.5mg/kg warfarin sodium
and 10g/kg Chuanxiong decoction), and WCO (a rat model of biliary drainage after
the gastric-administration of 0.5mg/kg warfarin sodium and 10g/kg Chuanxiong
decoction). The levels of warfarin and internal standard were quantified by LC
MS/MS. Comparisons between groups were performed according to the main
pharmacokinetic parameters calculated by the DAS 2.1.1 software. RESULTS: The
established LC-MS/MS method was specific, precise and rapid. The pharmacokinetic
parameters showed a significant difference between the WN and WO groups. There
were significant differences in the area under the curve (AUC0-t), peak
concentration (Cmax), total plasma clearance (CLz/F) and mean residence time
(MRT0-t) between the WCO and WCN groups; the AUC0-t of warfarin in the WCN group
was 2.42 times than that of the WN group (p<0.01); the WCO group displayed a
decreased to 61.6% in the Cmax compared the WO group (p<0.01). CONCLUSION:
Biliary drainage significantly influenced the disposition of warfarin, and
Chuanxiong significantly affected the warfarin disposition in rat plasma.
PMID- 27497636
TI - Protective effects of the roots of Angelica sinensis on strenuous exercise
induced sports anemia in rats.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sports anemia is a persistent and severe problem
in athletes owing to strenuous exercise-induced oxidative stress and hepcidin
upregulation. The roots of Angelica sinensis (AS), a familiar traditional Chinese
medicine, has been used for replenishing blood since antiquity. AIM OF THE STUDY:
To evaluate the effects of ethanolic AS extract in a 4-week study on sports
anemia in female Wistar rats. MATERIALS AND METHODS: To induce anemia, a
strenuous exercise protocol consisting of running and swimming was employed with
increasing intensity. Animals were randomly assigned to the following groups:
control group; strenuous exercise group; and strenuous exercise and AS extract
treated group (300mgkg-1d-1). After 4 weeks, rats underwent exhaustive swimming
and forelimb grip strength test. The blood biochemical markers and hepatic
antioxidant activities were determined. Hepatic interleukin-6 and muscle glycogen
were observed through immunohistochemical and Periodic acid-Schiff staining,
respectively. RESULTS: AS extract (consisting of ferulic acid, Z-ligustilide, and
n-butylidenephthalide) treatment improved forelimb grip strength and rescued
exercise-induced anemia by significantly elevating the red blood cell counts and
hemoglobin concentrations as well as hematocrit levels (p<0.05). AS modulated the
iron metabolism through decreasing serum hepcidin-25 concentrations by 33.0%
(p<0.05) and increasing serum iron levels by 34.3% (p<0.01). The hepatic injury
marker serum alanine aminotransferase concentrations were also reduced, followed
by increased antioxidant enzyme catalase expression in the liver (p<0.05).
Furthermore, substantial attenuation of hepatic interleukin-6 expression and
preservation of muscle glycogen content suggested the additional roles of AS
acting on sports anemia and physical performance. CONCLUSION: Our findings
evidenced a novel and promising therapeutic approach for AS treatment for
rescuing the anemic condition induced following 4 weeks of strenuous exercise.
PMID- 27497637
TI - Antitussive activity of the Schisandra chinensis fruit polysaccharide (SCFP-1) in
guinea pigs models.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill. (S.
chinensis), locally known as "Wuweizi", has been used in the treatment of chronic
cough as prescription medications of Traditional Chinese Medicine for thousands
of years. However, the components of antitussive activity of S. chinensis and the
mechanism are poorly understood. AIM OF THE STUDY: This study aims to investigate
the antitussive activity of polysaccharides extracted from S. chinensis.
MATERIALS AND METHODS: S. chinensis fruit polysaccharide-1 (SCFP-1) was extracted
by 95% ethanol and distilled water successively, and then the water extraction
was isolated with chromatographic columns. The preliminary characterization of
SCFP-1 was analyzed by gel permeation chromatography (GPC), gas chromatography
mass spectrometry (GC-MS) and some other recognized chemical methods. Antitussive
potential of SCFP-1 was estimated at dose of 250, 500, and 1000mg/kg respectively
by peroral administration in a guinea pigs model with cough hypersensitivity
induced by cigarette smoke (Chronic cough model) or acute cough guinea model
induced by citric acid (Acute cough model). Also, the time-dependent antitussive
effect of SCFP-1 were evaluated with acute cough model, and compared with
codeine. RESULTS: The molecular of SCFP-1 was 3.18*104Da, mainly being composed
of glucose and arabinose (66.5% and 29.4%, respectively). Peroral administration
of SCFP-1 at 250, 500, and 1000mg/kg showed remarkable suppressive effects
respectively on cough in both of chronic cough model and acute cough model.
Meanwhile, inflammatory cell in BALF and some typical characteristics of
nonspecific airway inflammation in animals exposed to CS was significantly
attenuated after pretreatment with SCFP-1. The cough suppression of SCFP-1 (500
mg/kg) stablly lasted during the whole 5 h of time-dependent experiment, while no
positive effect was observed after 300 min of oral administration of codeine.
CONCLUSIONS: SCFP-1 is one of the antitussive components of S. chinensis.
PMID- 27497638
TI - The total alkaloid fraction of bulbs of Fritillaria cirrhosa displays anti
inflammatory activity and attenuates acute lung injury.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Bulb of Fritillaria cirrhosa D.Don (BFC) has been
wildly used in China for a long time for folk medicine since its significant
therapeutic effects on respiratory diseases, such as cough, expectoration,
pneumonia and bronchial inflammation, which are related to respiratory
inflammatory response. However, there is a lack of investigation on the in vivo
anti-inflammatory properties of BFC. AIM OF THE STUDY: The aim of this study was
to evaluate the in vivo anti-inflammatory activity of the purified total alkaloid
fraction of BFC (TAF) by using different animal models of inflammation to provide
scientific evidence for its traditional use. MATERIALS AND METHODS: The total
alkaloid fraction from BFC was prepared by using H-103 resin column. Anti
inflammatory effect of TAF was evaluated by models of acetic acid-induced
capillary permeability accentuation, carrageenan-induced rat paw edema, cotton
pellet-induced granuloma formation and LPS-induced acute lung injury (ALI). The
level of cytokines (TNF, IL-6, IL-4 and IL-10) was measured by ELISA.
Histopathological analyses were performed by using hematoxylin and eosin
staining. RESULTS: TAF can inhibit acetic acid-induced capillary permeability
accentuation, carrageenan-induced paw edema, cotton pellet-induced granuloma
formation, suppress inflammatory cells recruitment and cytokine production in the
bronchoalveolar lavage fluid from LPS-induced ALI mice, and attenuate
pathological changes in the lung tissues of ALI mice. CONCLUSION: This study
provides scientific evidence for bulb of F. cirrhosa to treat respiratory
inflammation.
PMID- 27497639
TI - Identification of UQCRB as an oxymatrine recognizing protein using a T7 phage
display screen.
AB - ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Radix Sophorae
Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic
hepatitis B (CHB), and has the ability to clear heat and dampness from the body.
Oxymatrine is one of the major bioactive compounds extracted from Sophora
flavescens Aiton and constitutes more than 90% of the oxymatrine injection
commonly used for CHB treatment in clinics in China. AIM OF THE STUDY: We aim to
analyze the protein binding target of oxymatrine in treating CHB by screening a
T7 phage display cDNA library of human CHB and examine the biochemistry of
protein-ligand binding between oxymatrine and its ligands. MATERIALS AND METHODS:
A T7 phage cDNA library of human CHB was biopanned by affinity selection using
oxymatrine as bait. The interaction of oxymatrine with its candidate binding
protein was investigated by affinity assay, molecular docking, Isothermal
Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR). RESULTS: A
library of potential oxymatrine binding peptides was generated. Ubiquinol
cytochrome c reductase binding protein (UQCRB) was one of the candidate binding
proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the
oxymatrine group were significantly higher than that in the control group, biotin
group, and matrine group (p<0.05 or p<0.01). Three-dimensional structure modeling
of the UQCRB with oxymatrine showed that their binding interfaces matched and
oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino
acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and Glu91. The binding
affinity constant (Kb) from SPR was 4.2mM. The Kb from ITC experiment was 3.9mM
and stoichiometry was fixed as 1, which fit very well with the result of SPR. The
binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as
hydrogen bonds and polar interactions as the heat released was about 157kcal/mol
and DeltaG was less than zero. CONCLUSIONS: In this study, using the T7 phage
display system, we have identified UQCRB as a direct binding protein of
oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine
with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that
UQCRB is a potential target of oxymatrine in treating CHB. These results provide
new understanding into the mechanism of oxymatrine and insights into the strategy
on the treatment of CHB.
PMID- 27497640
TI - The effects of Qi Teng Xiao Zhuo granules, traditional Chinese medicine, on the
expression of genes in chronic glomerulonephritis rats.
AB - BACKGROUND AND AIM: Chronic glomerulonephritis (CGN) is a primary glomerular
disease that is related to immune-mediated inflammatory diseases. Qi Teng Xiao
Zhuo granules have been proposed as a prescription of traditional Chinese
medicine for treatment of CGN, but the comprehensive molecular mechanism
underlying this therapeutic effect is not clear to date. The aim of this study
was to evaluate and analyze the possible roles and molecular mechanisms of Qi
Teng Xiao Zhuo granule-mediated treatment of CGN induced by adriamycin in rats.
METHODS: For gene expression analysis, four samples of glomerular tissue from
rats in the Qi Teng Xiao Zhuo granule group and four samples each from the
adriamycin treated and control groups were hybridized with Agilent Rat 4*44K
whole genome microarrays. KEGG and Gene Ontology (GO) analyses and LIMMA, String
and Cytoscape software were used to analyze the functional microarray data and
screen differentially expressed genes. Hub genes were identified using Pathway
Studio software. Real-time PCR was performed to verify the selected genes.
RESULTS: Microarray gene expression analysis showed that Pnoc, Cacfd1, Fos,
Igll1, Lcn2, and Syk were among the most downregulated genes in the Qi Teng Xiao
Zhuo granule group compared with the adriamycin treated group, whereas Cyp2c7,
Hsd3b6, Acsm5, and Ugt2b15 were significantly upregulated. Functional analysis
demonstrated that metabolism of xenobiotics by cytochrome P450, the B cell
receptor signaling pathway, and cytokine-cytokine receptor interaction pathways
were significantly downregulated in the Qi Teng Xiao Zhuo granule group and that
GO terms related to positive regulation of immune response, immune response
activating signal transduction, cell differentiation, cell cycle, proliferation,
and adhesion were significantly affected. Fos and Syk were considered to be
potential hub genes. CONCLUSIONS: In the adriamycin-induced CGN rat model,
comprehensive molecular mechanisms were involved with complex gene expression
alterations containing many altered pathways and GO terms. However, how Qi Teng
Xiao Zhuo granules regulate these events warrants further investigation.
PMID- 27497641
TI - A plasma modified cellulose-chitosan porous membrane allows efficient DNA binding
and provides antibacterial properties: A step towards developing a new DNA
collecting card.
AB - In forensic DNA analyses, biological specimens are collected and stored for
subsequent recovery and analysis of DNA. A cost-effective and efficient DNA
recovery approach is therefore a need. This study aims to produce a plasma
modified cellulose-chitosan membrane (pCE-CS) that efficiently binds and retains
DNA as a potential DNA collecting card. The pCE-CS membrane was produced by a
phase separation of ionic liquid dissolving CE and CS in water with subsequent
surface-modification by a two-step exposure of argon plasma and nitrogen gas.
Through plasma modification, the pCE-CS membrane demonstrated better DNA
retention after a washing process and higher rate of DNA recovery as compared
with the original CE-CS membrane and the commercial FTA card. In addition, the
pCE-CS membrane exhibited anti-bacterial properties against both Escherichia coli
and Staphylococcus aureus. The results of this work suggest a potential function
of the pCE-CS membrane as a DNA collecting card with a high recovery rate of
captured DNA.
PMID- 27497642
TI - The origin of unknown source DNA from touched objects.
AB - The presence of DNA in a criminal investigation often requires scrutiny in
relation to how it came to be where it was found. There is a paucity of data with
respect to the extent to which one can assume that the last person handling an
object, which has previously been touched by others, will contribute to the DNA
profile generated from it. There are limited data in detailing the extent to
which any foreign DNA is picked-up from a previously touched object and
transferred to subsequently touched objects. This study focuses on DNA transfer
and persistence on a knife handle after multiple handlings with the knife by
different individuals soon after each other, as well as handprints left on flat
DNA-free surfaces immediately after touching a knife handle with a known history
of prior handling. The profiles of later handlers of a knife are more prominent
than earlier handlers; however, the last handler is not always the major
contributor to the profile. Proportional contributions to the profiles retrieved
from knife handles vary depending on the individuals touching the knife handle.
They can also vary when knife handles have been handled in the same manner by the
same individuals in the same sequence on different occasions. Hands readily
pickup DNA left on objects by others and transfer it to subsequently touched
objects. The quantity of foreign DNA picked up by a hand and deposited on
subsequently touched objects diminishes as more DNA-free objects are handled soon
after each other. Caution is advised when considering how DNA from different
individuals may have been transferred to the object from which it was collected.
PMID- 27497643
TI - Massively parallel sequencing of 10 autosomal STRs in Chinese using the ion
torrent personal genome machine (PGM).
AB - Massively parallel sequencing (MPS) technology is gaining interest in the
forensic community. The capabilities of high throughput and simultaneously
analyses of many markers enable MPS as an attractive method for human forensics.
Recent studies have demonstrated the successful application of the MPS system to
short tandem repeat (STR) typing. However, not only DNA sequence variations in
the repeat regions of STR but also in flanking regions are required to facilitate
profiles sharing with capillary electrophoresis (CE)-based typing method. In this
study, we constructed a multiplex PCR system for the MPS analysis of 10 autosomal
STR loci (D13S317, D16S539, D19S433, D2S441, D3S1358, D5S818, D6S1043, D7S820,
TH01, TPOX) by designing amplicons in the size range of 168-273 base pairs.
Sequencing results from 165 Chinese unrelated individuals demonstrated 11
variations in the flanking regions between amplification primer binding sites and
core repeat motifs. In addition, three loci, D13S317, D5S818, and D7S820,
displayed variants adjacent to the core repeats and caused discordances between
sequence-based and length-based typing results. Four loci (D3S1358, D2S441,
D19S433 and D7S820) demonstrated an increased allele number using MPS-based
typing. This study demonstrated that STR typing by MPS could provide more genetic
information from both repeat and flanking regions of STR loci, thus improving the
diversity and discrimination power of the system in forensic detection.
PMID- 27497644
TI - Genetic mapping of 15 human X chromosomal forensic short tandem repeat (STR) loci
by means of multi-core parallelization.
AB - Typing of X chromosomal short tandem repeat (X STR) markers has become a standard
element of human forensic genetic analysis. Joint consideration of many X STR
markers at a time increases their discriminatory power but, owing to physical
linkage, requires inter-marker recombination rates to be accurately known. We
estimated the recombination rates between 15 well established X STR markers using
genotype data from 158 families (1041 individuals) and following a previously
proposed likelihood-based approach that allows for single-step mutations. To meet
the computational requirements of this family-based type of analysis, we modified
a previous implementation so as to allow multi-core parallelization on a high
performance computing system. While we obtained recombination rate estimates
larger than zero for all but one pair of adjacent markers within the four
previously proposed linkage groups, none of the three X STR pairs defining the
junctions of these groups yielded a recombination rate estimate of 0.50.
Corroborating previous studies, our results therefore argue against a simple
model of independent X chromosomal linkage groups. Moreover, the refined
recombination fraction estimates obtained in our study will facilitate the
appropriate joint consideration of all 15 investigated markers in forensic
analysis.
PMID- 27497645
TI - Improving empirical evidence on differentiating closely related men with RM Y
STRs: A comprehensive pedigree study from Pakistan.
AB - Y-chromosomal short tandem repeat (Y-STR) markers are commonly used in forensic
genetics. Male-specific haplotypes provided by commercial Y-STR kits allow
discriminating between many - but not all - unrelated men, while they mostly fail
to separate related ones. Aiming to improve male relative and paternal lineage
differentiation, a set of 13 rapidly-mutating (RM) Y-STRs was previously
identified and introduced to forensic Y-chromosome analysis. Recently, their
value was highlighted by separating 99% of over 12,200 unrelated men from 111
global populations, as well as 29% of over 2500 male relative pairs, the vast
majority were father-sons. Here, we provide improved empirical evidence on
differentiating closely related men with RM Y-STRs, most notably beyond father
sons, where previous data were limited. After careful quality control including
genetic relationship testing, we used 572 Pakistani men belonging to 99 2-4
generation pedigrees covering 1568 pairs of men related by 1-6 meioses. Of those,
45% were differentiated by one or more of the 13 RM Y-STR markers. In contrast,
only 14.7% of a subset of 1484 pairs from 94 pedigrees were separated by the
commercial AmpFlSTR Y-filer kit. Combining previously published and new data, an
overall differentiation rate of 35.3% was revealed for the RM Y-STR set based on
4096 pairs of men related by 1-20 meioses, compared to 9.6% with Y-filer based on
3645 pairs. Using father-son pair data from the present and previous studies, we
provide updated RM Y-STR mutation rates. Locus-specific mutation rates ranged
from 2.0*10-3 (7.0*10-4-4.3*10-3) to 6.9*10-2 (6.1*10-2-7.9*10-2) based on 2741
3143 meioses, with an average rate across all 13 RM Y-STR markers of 1.8*10-2
(1.7*10-2-1.9*10-2) based on 800 mutations from 44,922 meioses. The high
haplotype diversity (h=0.9996) we observed among the unrelated men (N=105)
underlines the value of this RM Y-STR set to differentiate paternal lineages even
from endogamous populations such as from Pakistan.
PMID- 27497646
TI - The neuromotor effects of transverse friction massage.
AB - BACKGROUND: Transverse friction massage (TFM), as an often used technique by
therapists, is known for its effect in reducing the pain and loosing the scar
tissues. Nevertheless, its effects on neuromotor driving mechanism including the
electromechanical delay (EMD), force transmission and excitation-contraction (EC)
coupling which could be used as markers of stiffness changes, has not been
computed using ultrafast ultrasound (US) when combined with external sensors.
AIM: Hence, the aim of this study was to find out produced neuromotor changes
associated to stiffness when TFM was applied over Quadriceps femoris (QF) tendon
in healthy subjcets. METHODS: Fourteen healthy males and fifteen age-gender
matched controls were recruited. Surface EMG (sEMG), ultrafast US and Force
sensors were synchronized and signals were analyzed to depict the time delays
corresponding to EC coupling, force transmission, EMD, torque and rate of force
development (RFD). RESULTS: TFM has been found to increase the time corresponding
to EC coupling and EMD, whilst, reducing the time belonging to force transmission
during the voluntary muscle contractions. CONCLUSIONS: A detection of the
increased time of EC coupling from muscle itself would suggest that TFM applied
over the tendon shows an influence on changing the neuro-motor driving mechanism
possibly via afferent pathways and therefore decreasing the active muscle
stiffness. On the other hand, detection of decreased time belonging to force
transmission during voluntary contraction would suggest that TFM increases the
stiffness of tendon, caused by faster force transmission along non-contractile
elements. Torque and RFD have not been influenced by TFM.
PMID- 27497647
TI - Factors Associated With Timing of Return to Intercourse After Obstetric Anal
Sphincter Injuries.
AB - INTRODUCTION: The impact of obstetric perineal trauma on timing of return to
intercourse is unclear, although sexual desire is clearly decreased in these
women. In addition, studies examining timing of return to intercourse are cross
sectional and therefore cannot delineate potential reasons that patients might
delay return to intercourse. AIM: To identify factors associated with delayed
return to intercourse after obstetric anal sphincter injuries. METHODS: This was
a planned secondary analysis of a prospective cohort study of women sustaining
obstetric anal sphincter injuries during delivery of a full-term singleton
infant. Patients completed the Fecal Incontinence Severity Index at every
postpartum visit (1, 2, 6, and 12 weeks) and the Pelvic Organ
Prolapse/Incontinence Sexual Questionnaire-12 once resuming vaginal intercourse.
Intercourse was considered "delayed" if patients did not resume intercourse by
the 12-week visit. This cutoff was chosen because it was subsequent to the 6-week
visit, when patients were instructed to return to normal pelvic activity.
Continuous variables were compared using the Student t-test (parametric) or Mann
Whitney U-test (non-parametric). The chi(2) test was used for categorical
variables. Statistical significance was assigned with a P value less than .05.
MAIN OUTCOME MEASURES: Primary outcome measurements were differences in pelvic
floor symptoms on validated surveys between the "delayed" and "not-delayed"
groups at the first postpartum visit and at the time the subjects returned to
intercourse. We used the Patient Health Questionnaire-9 for depression, the
Urinary Distress Inventory-6 and Incontinence Impact Questionnaire-7 for urinary
symptoms, the visual analog scale for pain, the Fecal Incontinence Severity Index
for bowel symptoms, and the Pelvic Organ Prolapse/Incontinence Sexual
Questionnaire-12 at the return to intercourse visit only. RESULTS: One hundred
ninety-nine women were included in this analysis. Most were Caucasian (77%) and
primiparous (86%). One hundred nineteen women (60%) did not resume vaginal
intercourse until after the 12-week visit and were deemed "delayed." Patients who
delayed intercourse scored higher on the Fecal Incontinence Severity Index (more
anal incontinence) than those who resumed intercourse before 12 weeks (15.4 +/-
12.3 vs 12.0 +/- 12.8, P = .02). The delayed group also had worse sexual
function, shown as lower Pelvic Organ Prolapse/Incontinence Sexual Questionnaire
12 scores (35.4 +/- 5.9 vs 38.4 +/- 4.1, P <= .001) and persistently higher Fecal
Incontinence Severity Index scores (4.1 +/- 7.3 vs 1.6 +/- 4.4, P = .001), at the
first visit after returning to intercourse. CONCLUSION: Patients with obstetric
anal sphincter injuries who do not resume intercourse by 12 weeks postpartum
report more severe anal incontinence symptoms and worse sexual function after
return to coitus.
PMID- 27497648
TI - Simultaneous quantification of tenofovir, emtricitabine, rilpivirine,
elvitegravir and dolutegravir in mouse biological matrices by LC-MS/MS and its
application to a pharmacokinetic study.
AB - Combination antiretroviral (cARV) treatment is more common in human
immunodeficiency virus (HIV) infection. In many instances, treatment regimen
includes two or more combination of drugs from six different classes. Some of the
antiretroviral combination medications are under study at preclinical and
clinical stages. A precise method is required to quantify the drug concentration
in biological matrices to study pharmacokinetic behavior and tissue distribution
profile in animals and/or humans. We have developed and validated a sensitive and
precise liquid chromatography-tandem mass spectrometry method for simultaneous
quantification of selected antiretroviral drugs, tenofovir (TNF), emtricitabine
(FTC), rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) in mouse
biological matrices. This method involves a solid phase extraction, simple
isocratic chromatographic separation using Restek Pinnacle DB BiPh column
(50mm*2.1mm, 5MUm) and mass spectrometric detection by an API 3200 Q Trap
instrument. The total run time for each sample was 6min. The method was validated
in the concentration range of 5-2000ng/mL for FTC, RPV, DTG, EVG and 10-4000ng/mL
for TNF respectively with correlation coefficients (r(2)) higher than 0.9976. The
results of intra and inter-run assay precision and accuracy were within
acceptance limits for all the five analytes. This method was used to support the
study of pharmacokinetics and tissue distribution profile of nanoformulated
antiretroviral drugs in mice.
PMID- 27497649
TI - An integrated approach for profiling oxidative metabolites and glutathione
adducts using liquid chromatography coupled with ultraviolet detection and triple
quadrupole-linear ion trap mass spectrometry.
AB - The use of liquid chromatography (LC) coupled with triple quadrupole linear ion
trap (Qtrap) mass spectrometry (MS) for both quantitative and qualitative
analysis in drug metabolism and pharmacokinetic studies is of great interest.
Here, a new Qtrap-based analytical methodology for simultaneous detection,
structural characterization and semi-quantitation of in vitro oxidative
metabolites and glutathione trapped reactive metabolites was reported. In the
current study, combined multiple ion monitoring and multiple reaction monitoring
were served as surveying scans to trigger product ion spectral acquisition of
oxidative metabolites and glutathione adduct, respectively. Then, detection of
metabolites and recovery of their MS/MS spectra were accomplished using multiple
data mining approaches. Additionally, on-line ultraviolet (UV) detection was
employed to determine relative concentrations of major metabolites. Analyses of
metabolites of clozapine and nomifensine in rat liver microsomes not only
revealed multiple oxidative metabolites and glutathione adducts, but also
identified their major oxidative metabolism and bioactivation pathways. The
results demonstrated that the LC/UV/MS method enabled Qtrap to perform the
comprehensive profiling of oxidative metabolites and glutathione adducts in
vitro.
PMID- 27497650
TI - (1)H-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti
inflammatory drug-induced adverse effects in rats.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs), which are globally prescribed,
exhibit mainly anti-inflammatory and analgesic effects but also can cause adverse
effects including gastrointestinal erosions, ulceration, bleeding, and
perforation. The purpose of this study was to investigate surrogate biomarkers
associated with the gastrointestinal (GI) damage caused by NSAID treatment using
pattern recognition analysis of (1)H-nuclear magnetic resonance ((1)H NMR)
spectra of rat urine. Urine was collected for 5h after oral administration of the
following NSAIDs at low or high doses: acetylsalicylic acid (10 or 200mgkg(-1)),
diclofenac (0.5 or 15mgkg(-1)), piroxicam (1 or 10mgkg(-1)), indomethacin (1 or
25mgkg(-1)), or ibuprofen (10, or 150mgkg(-1)) as nonselective COX inhibitors and
celecoxib (10 or 100mgkg(-1)) as a COX-2 selective inhibitor. The urine was
analyzed using 500MHz (1)H NMR for spectral binning and targeted profiling and
the level of gastric damage was examined. The nonselective COX inhibitors caused
severe gastric damage while no lesions were observed in the celecoxib-treated
rats. The (1)H NMR urine spectra were divided into spectral bins (0.04ppm) for
global profiling, and a total of 44 endogenous metabolites were assigned for
targeted profiling. Multivariate data analyses were performed to recognize the
spectral pattern of endogenous metabolites related to NSAIDs using partial least
square-discrimination analysis (PLS-DA). The (1)H NMR spectra clustered
differently according to gastric damage score in global profiling. In targeted
profiling, the endogenous metabolites of citrate, allantoin, 2-oxoglutarate,
acetate, benzoate, glycine, and trimethylamine N-oxide were selected as putative
biomarkers for gastric damage caused by NSAIDs. These putative biomarkers might
be useful for predicting the risk of adverse effects caused by NSAIDs in the
early stage of drug development process.
PMID- 27497651
TI - Development and validation of a bioanalytical method for five antidepressants in
human milk by LC-MS.
AB - The use of medications during lactation is a common practice; however,
pharmacological treatments impose serious doubts to both professionals and
nursing mothers regarding the safety of drugs used during this period. Most of
drugs are excreted in breast milk and there is great variability in the amount of
analytes that can be received by the infant. Dilemmas about breastfeeding arise
most commonly in relation to postpartum depression. Depression is a major
clinical problem during the postpartum period and the vulnerability to onset or
recurrence of depressive symptoms increases the possibility of psychotropic drug
use during lactation. Selective inhibitors of serotonin reuptake are commonly
prescribed for the treatment of depressive disorders, including fluoxetine,
sertraline, citalopram, and paroxetine. A validated bioanalytical method using
liquid chromatography coupled to mass spectrometry was developed and validated
for determination of antidepressants in human milk following protein precipation.
The bioanalytical method was successfully applied to assess milk samples from
nursing mothers. From found concentrations, infant absolute (4.36
12.26MUg/kg/day) and relative dose (0.60-2.90%,) were estimated and low values
were obtained indicating safe use during laction. However, other factors such as
complemantary feeding and hepatic or renal disorders in the infant should be
considered.
PMID- 27497652
TI - Identification, synthesis, isolation and characterization of formulation related
impurity of Gabapentin.
AB - An unknown impurity was observed during stability studies of Gabapentin capsules.
This impurity has been identified, synthesized, isolated and characterized using
modern analytical tool. The novel impurity was confirmed as adduct of Gabapentin
and lactose; an excipient used in formulation. The elucidated impurity was
further confirmed by its synthesis, which was formed due to Maillard reaction and
Amadori rearrangement.
PMID- 27497653
TI - Bioactivity evaluation-based ultra high-performance liquid chromatography coupled
with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry
and novel distinction of multi-subchemome compatibility recognition strategy with
Astragali Radix-Fructus Corni herb-pair as a case study.
AB - The approach to investigate traditional Chinese medicine (TCM) is still in its
infancy and has been facing enormous challenge. In this paper, a generally
applicable strategy was developed for investigation on TCM systematically with an
introduced interesting idea about a novel research system which called
subchemome. A representative herb-pair, Astragali Radix-Fructus Corni, was
successfully employed to expound this novel strategy. Firstly, subchemomes were
prepared individually by applying the suitable column chromatography, each of
them was detected by UV spectrophotometer or HPLC-DAD detector. The components in
each part were then identified based on the mass spectrometric fragmentation
patterns and tandem mass spectrometric data by using UHPLC-Q-TOF-MS. Using renal
mesangial cell (RMC) viability assay as the evaluation of the pharmacological
activity of each group, we developed the new mini herbal formulae aimed at
diabetic nephropathy and identified fifteen marker components between the group
of new mini herbal formulae and other groups from the angle of the constituent,
and then explored the effects of new mini herbal formulae from another angle of
the molecular mechanism. Overall, the presently developed strategy should be
beneficial and widely used in the investigation on TCM from a new perspective.
PMID- 27497654
TI - UHPLC-MS/MS method with protein precipitation extraction for the simultaneous
quantification of ten antihypertensive drugs in human plasma from resistant
hypertensive patients.
AB - Today the management of resistant hypertension is a critical health problem: the
main difficulty on this field is the discrimination of cases of poor therapeutic
adherence from cases of real resistance. This gives rise to the need of high
throughput and reliable quantification methods for the Therapeutic Drug
Monitoring (TDM) of antihypertensive drugs. The aim of this work was the
development and validation of a UHPLC-Tandem mass spectrometry assay for this
application and its use in plasma from patients with resistant hypertension. The
novelty of this method resides in the ability to simultaneously quantify a wide
panel of antihypertensive drugs: amlodipine, atenolol, clonidine, chlortalidone,
doxazosin, hydrochlorothiazide, nifedipine, olmesartan, ramipril and telmisartan.
Moreover, this method stands out for its simplicity and cheapness, resulting
feasible for clinical routine. Both standards and quality controls were prepared
in human plasma. After the addition of internal standard, each sample underwent
protein precipitation with acetonitrile and was then dried. Extracts were
resuspended in water:acetonitrile 90:10 (0.05% formic acid) and then injected
into the chromatographic system. Chromatographic separation was performed on an
Acquity((r)) UPLC HSS T3 1.8MUm 2.1*150mm column, with a gradient of water and
acetonitrile, both added with 0.05% formic acid. Accuracy, intra-day and inter
day precision fitted FDA guidelines for all analytes, while matrix effects and
recoveries resulted stable between samples for each analyte. Finally, we tested
this method by monitoring plasma concentrations in 22 hypertensive patients with
good results. This simple analytical method could represent a useful tool for the
management of antihypertensive therapy.
PMID- 27497655
TI - Analytical comparison of a US generic enoxaparin with the originator product: The
focus on comparative assessment of antithrombin-binding components.
AB - Enoxaparin sodium, a low-molecular-weight heparin (LMWH) prepared from porcine
intestinal heparin, is widely used for the prevention and treatment of venous
thromboembolism. The antithrombotic activity of heparin is mediated mainly
through its activation of antithrombin (AT) and subsequent inhibition of
coagulation factors. Heparin is a complex heteropolymer and the sulfation pattern
of its alternating uronic acid and glucosamine sugar units is a major factor
influencing its biological activity. The manufacturing process itself is
associated with the introduction of exogenous microheterogeneities that may
further affect its biological efficacy. This is important since enoxaparin is
prepared by depolymerizing the heparin with the aim of optimizing its biological
activity and safety. Changes during its manufacture could thus affect its
biological activity and safety. The current study was performed to assess
potential differences between the originator enoxaparin and a new generic
enoxaparin commercialized by Teva. Heparinase digestion, AT affinity
chromatography, gel permeation chromatography, anion exchange chromatography, and
nuclear magnetic resonance methodologies were used. The results indicated
differences in oligosaccharides related to the cleavage selectivity around the
heparin AT-binding sequences of the Teva Enoxaparin Sodium Injection, USP and the
originator Sanofi enoxaparin. These differences influence the strength of the AT
binding affinity of the individual oligosaccharides, their ability to activate AT
and, therefore, the inhibitory potency on the proteases of the coagulation
cascade. This study, together with other published analytical reports, describes
specific compositional differences between generics and originator LWMHs.
However, it is yet to be established whether such variations might have any
clinical relevance.
PMID- 27497656
TI - Molecular characterization of a clinical Haemophilus parainfluenzae isolate with
cefotaxime resistance and decreased susceptibility to fluoroquinolones.
AB - We report an H. parainfluenzae clinical isolate resistant to cefotaxime and with
decreased susceptibility to ciprofloxacin recovered from a patient with cystic
fibrosis. The isolate had elevated MICs of ampicillin (256mg/L), amoxicillin
clavulanate (8mg/L), cefuroxime (8mg/L) and cefotaxime (4mg/L), and showed a beta
lactamase-producing amoxicillin-clavulanic acid-resistant (BLPACR) phenotype. A
blaTEM-1 plus five amino acid substitutions in the PBP3 were found: Ser385Thr,
Val511Ala, Ile519Val, Asn526Lys and Asp551Leu. MIC of ciprofloxacin was 0.5mg/L,
and substitutions in gyrA (Ser84Tyr) and parC (Ser84Phe) genes were detected.
PMID- 27497657
TI - Identification of a dominant Chlamydia trachomatis strain in patients attending
sexual transmitted infection clinic and female sex workers in Tunisia using a
high resolution typing method.
AB - BACKGROUND: The distribution of Chlamydia trachomatis genotypes in Tunisia was
previously studied using the reverse hybridization method. In this study, we used
multilocus sequence typing (MLST) to describe Chlamydia trachomatis genetic
diversity among heterosexual populations in Tunisia. The obtained sequence types
(STs) were compared with those from a heterosexual population from Amsterdam, the
Netherlands. METHODS: Clinical Tunisian patients and female sex workers provided
107 Chlamydia trachomatis positive samples that were used for MLST. Samples from
256 heterosexuals visiting the Amsterdam STI clinic were included as a reference
group. Six highly variable genetic regions including the ompA gene were amplified
and sequenced. The ST numbers were derived from a Chlamydia typing database
(http://mlstdb.uu.se) and used to draw minimum spanning trees. RESULTS: ompA
sequencing detected 7 genotypes among the Tunisian populations of which genotype
E was the most prevalent (66.3%). This genotype E resolved into 23 different STs
and among these the ST3 was predominant (53.5%). MLST displayed 43 STs, of which
28 (65%) were new in the database. Minimum spanning tree analysis of all Tunisian
samples identified 4 clusters of which one formed a clonal cluster with samples
presenting the most prevalent ST3. When comparing samples from the Tunisian and
Dutch populations in one minimum spanning tree, there was little overlap between
the Chlamydia trachomatis samples. CONCLUSION: The CT-hrMLST scheme allowed us to
identify that the Tunisian distribution was dominated by one genotype E (ST3)
strain which is also highly prevalent in many other countries worldwide.
PMID- 27497658
TI - Obesity and novel cardiovascular markers in a population without diabetes and
cardiovascular disease in China.
AB - OBJECTIVE: To investigate associations of novel cardiovascular markers with
obesity in a general population. METHODS: A total of 9361 individuals without
diabetes or cardiovascular disease were studied between 2009 and 2012 in China.
High-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic
peptide (NT-proBNP), brachial-ankle pulse wave velocity (baPWV), pulse pressure,
and central systolic blood pressure (cSBP) were assessed according to body mass
index (BMI) levels and different BMI/metabolic syndrome (MetS) combinations.
RESULTS: 'Levels of hs-cTnT, baPWV, pulse pressure, and cSBP increased across BMI
levels. Obesity was positively associated with these markers in multivariate
models (P<0.05 for all). When stratified by MetS, these associations remained
significant in the non-MetS group, and compared with normal weight participants,
the obese participants had 1.87 (95% confidence interval: 1.48, 2.36), 1.27
(1.02, 1.57), 1.89 (1.39, 2.57), and 2.71 (2.11, 3.47) fold risks for having
elevated hs-cTnT, baPWV, pulse pressure, and cSBP, respectively, and had 1.61
(1.26, 2.05), 1.75 (1.27, 2.42), 2.45 (1.46, 4.11), and 3.14 (2.13, 4.62) fold
risks for having 1, 2, 3, and 4 elevated cardiovascular markers, respectively;
while no relationship was observed between obesity and these novel markers in the
MetS group, after multivariate adjustment. These results were unchanged when
using a waist-hip ratio, body fat per cent, and visceral adiposity index to
redefine obesity. CONCLUSIONS: Obesity was positively associated with novel
cardiovascular markers (except NT-proBNP) in participants without MetS rather
than in participants with MetS. Obese participants without MetS also had higher
odds of having more number of elevated cardiovascular markers.
PMID- 27497659
TI - Reclaiming the streets for people: Insights from Ciclovias Recreativas in Latin
America.
AB - The Ciclovias comprise worldwide programs in which streets are closed to motor
vehicles and open to individuals for leisure activities. Currently, 93% of the
regular programs are in Latin American countries (LAC). The aims of this study
were to describe the characteristics of regular Ciclovias in 7 LAC and to analyze
the factors that influence the sustainability and scaling-up of five case
studies. We conducted a survey of 67 Ciclovias in 2014-2015. In addition, we
conducted semi-structured interviews with current and former program coordinators
and reviewed policy documents from Ciclovias in 5 LAC. The greatest expansion of
Ciclovias has occurred since 2000. The number of participants per event ranged
from 40 to 1,500,000 (mean 41,399+/-193,330; median 1600), and the length ranged
from 1 to 113.6km (mean 9.1+/-16.4; median 3). Ciclovia routes connect low-middle
and high income neighborhoods (89.3%), and include the participation of minority
populations (61.2%). The main complementary activity offered was physical
activity (PA) classes (94.0%), and 80.0% of the programs included strategies to
promote biking. All five case studies met definitions for sustainability and
scaling-up. All programs shared some level of government support, alliances,
community appropriation, champions, compatibility with the mission of the host
organization, organizational capacity, flexibility, perceived benefits, and
funding stability. However, they differed in operational conditions, political
favorability, sources of funding, and number of alliances. The Ciclovias of LAC
showed heterogeneity within their design and sustainability factors. Both their
heterogeneity and flexibility to adjust to changes make them promising examples
of socially inclusive programs to promote PA.
PMID- 27497660
TI - The influence of prescription opioid use duration and dose on development of
treatment resistant depression.
AB - Long-term prescription opioid use is associated both with new-onset and
recurrence of depression. Whether chronic opioid use interferes with depression
management has not been reported, therefore we determined whether patients'
longer duration of opioid use and higher opioid dose are associated with new
onset treatment resistant depression (TRD) after controlling for confounding from
pain and other variables. Data was obtained from Veteran Health Administration
(VHA) de-identified patient medical records. We used a retrospective cohort
design from 2000-2012. Eligible subjects (n=6169) were 18-80years of age, free of
cancer and HIV, diagnosed with depression and opioid-free for the 24-month
interval prior to the observation period. Duration of a new prescription for
opioid analgesic was categorized as 1-30days, 31-90days and >90days. Morphine
equivalent dose (MED) during follow-up categorized as <=50mg versus >50mg per
day. Pain and other sources of confounding were controlled by propensity scores
and inverse probability of treatment weighting. Cox proportional hazard models
were computed to estimate the association between duration and dose of opioid and
onset of TRD. After controlling for confounding by weighting data, opioid use for
31-90days and for >90days, compared to 1-30days, was significantly associated
with new onset TRD (HR=1.25; 95% CI: 1.09-1.45 and HR=1.52; 95% CI: 1.32-1.74,
respectively). MED was not associated with new onset TRD. The risk of developing
TRD increased as time spent on opioid analgesics increased. Long-term opioid
treatment of chronic pain may interfere with treatment of depression.
PMID- 27497661
TI - Development and application of a general plasmid reference material for GMO
screening.
AB - The use of analytical controls is essential when performing GMO detection through
screening tests. Additionally, the presence of taxon-specific sequences is
analyzed mostly for quality control during GMO detection. In this study, 11
commonly used genetic elements involving three promoters (P-35S, P-FMV35S and P
NOS), four marker genes (Bar, NPTII, HPT and Pmi), and four terminators (T-NOS, T
35S, T-g7 and T-e9), together with the reference gene fragments from six major
crops of maize, soybean, rapeseed, rice, cotton and wheat, were co-integrated
into the same single plasmid to construct a general reference plasmid pBI121
Screening. The suitability test of pBI121-Screening plasmid as reference material
indicated that the non-target sequence on the pBI121-Screening plasmid did not
affect the PCR amplification efficiencies of screening methods and taxon-specific
methods. The sensitivity of screening and taxon-specific assays ranged from 5 to
10 copies of pBI121-Screening plasmid, meeting the sensitivity requirement of GMO
detection. The construction of pBI121-Screening solves the lack of a general
positive control for screening tests, thereby reducing the workload and cost of
preparing a plurality of the positive control.
PMID- 27497662
TI - Increased cryosurvival of osteosarcoma cells using an amphipathic pH-responsive
polymer for trehalose uptake.
AB - Amphipathic pH-responsive polymers have shown to increase the permeability of
cell membranes to trehalose hence improving the cryopreservation of mammalian
cells. However, the trafficking of both the polymer and trehalose across the cell
membrane has not yet been thoroughly analysed. The objective of this study was to
investigate the effect on cryopreservation of the trafficking of the disaccharide
trehalose along PP-50, an amphipathic polymer, through an osteosarcoma cell line
(SAOS-2). Confocal microscopy analysis confirmed the presence of intracellular
labelled trehalose only when incubated in the presence of PP-50. Further analysis
confirmed that both trehalose and PP-50 localised in the cytoplasm, accumulated
mainly in the perinuclear area. Quantitative analysis of the colocalisation
between trehalose and PP-50 showed Pearson and Manders coefficients of 0.862 +/-
0.008 and 0.766 +/- 0.033, respectively, suggesting a high degree of
intracellular colocalisation between these molecules. Cryopreserved cells pre
incubated with trehalose and PP-50 showed increased cryosurvival when compared
with cells pre-incubated in the absence of the polymer. PP-50 showed to be
directly involved in the uptake of trehalose, a critical characteristic towards
use in cryopreservation and biomedical applications.
PMID- 27497663
TI - Vitrification at Day3 stage appears not to affect the methylation status of
H19/IGF2 differentially methylated region of in vitro produced human blastocysts.
AB - One of the most widely used assisted reproductive technology (ART) is
vitrification. The aim of this study is to evaluate DNA methylation of H19/IGF2
differentially methylation region (DMR) in in vitro produced human blastocysts
derived from non-vitrified and vitrified day3 embryos. Day3 embryos derived from
ICSI cycles from fertile couples referring for family balancing program were
either biopsied or vitrified/warmed and subsequently biopsied. Following biopsy,
embryos were cultured to day 5. Day5 blastocysts with desired sex were
transferred or vitrified for future use. Blastocysts with un-desired sex were
donated for research. The assessment of the embryos was performed in two non
vitrified and vitrified groups. Methylation level of H19/IGF2 DMR was analysed by
bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this
region. Results showed that the overall methylated CpGs percentages of this
region in the vitrified and non-vitrified groups were 35.3% +/- 3.6 and 38.27 +/-
4.1%, respectively. The difference between the two groups was not significant.
Vitrification of day3 embryo appears to have no adverse effect on DNA methylation
status of H19/IGF2 DMR of embryos cultured in vitro to blastocyst stage. These
data may have implications for performing frozen embryo cycles transfer instead
of fresh embryo transfer cycles, owing to the naturally synchronized uterus and
subsequently improved endometrial receptivity in frozen embryo transfer instead
of imbalanced hormonal milieu in fresh embryo transfer cycles.
PMID- 27497664
TI - Kisspeptin2 stimulates the HPG axis in immature Nile tilapia (Oreochromis
niloticus).
AB - It has been suggested that kisspeptin influences reproduction and onset of
puberty in fishes. Unlike mammals, which produce only one kisspeptin (Kiss1),
some teleosts have two, Kiss1 and Kiss2, both thought to be involved in the
stimulation of gonadotropin (GTH) secretion. In Nile tilapia (Oreochromis
niloticus), however, only Kiss2 has been identified so far. The effect of Kiss2
on GTH release varies significantly depending on species and reproductive stage.
Furthermore, its physiological function in this species is not clearly defined.
In this study, kiss2 gene expression profiles were examined using quantitative
real-time PCR (qRT-PCR) in the brain, pituitary, and gonads of Nile tilapia at
different reproductive stages (male: immature, pre-spermiation, post-spermiation;
female: immature, pre-spawning, post-spawning). The kiss2 mRNA expression
profiles of the brain, pituitary, and gonads of both sexes shared a similar
pattern their expression was significantly higher at the immature stage than at
the mature or post-spawning stages, implying it is involved in early gonadal
maturation in this species. To investigate the effect of kisspeptin on the
hypothalamus-pituitary-gonad (HPG) axis in vivo, synthetic kisspeptin2
(FNYNPLSLRF) was injected into immature male and female tilapia intraperitoneally
(i.p.) at a dose of 200pmol/g body weight. The results showed that synthetic
Kiss2 administration increased the expression of GnRH I, fshbeta and lhbeta mRNA
in the brain and increased 17beta-estradiol (E2) and 11-ketotestosterone (11-KT)
levels in the plasma. These results suggest that Kiss2 stimulates the expression
of GnRH and GTH genes in immature Nile tilapia.
PMID- 27497665
TI - DNA methylation in a sea lamprey vasotocin receptor gene promoter correlates with
tissue- and life-stage-specific mRNA expression.
AB - The jawless vertebrate sea lamprey (Petromyzon marinus) genome has a different
structure from both invertebrates and jawed vertebrates featuring high guanine
cytosine (GC) content. This raises the question of whether DNA methylation of
cytosine-guanine (CpG) dinucleotides could function to regulate lamprey gene
transcription. We previously characterized a lamprey arginine vasotocin (AVT)
receptor gene (Pm807) possessing characteristics of both arginine vasopressin
(AVP) V1A and oxytocin (OXT) receptor genes of jawed vertebrates. Lamprey Pm807
mRNA is highly expressed in adult heart and larval liver but not expressed in
adult liver. Using high-resolution melt (HRM) PCR on bisulfite-converted DNA, we
pinpointed a region with tissue-specific differences in DNA melt characteristics,
indicating differences in methylation level. Sequencing revealed a pattern of
methylation at specific CpGs at consistently higher levels in adult heart and
larval liver than adult liver. These CpGs are associated with putative
transcription factor binding sequences organized similarly to functional OXTR
promoters in mammals, suggesting functional similarity in lamprey gene
transcription regulation.
PMID- 27497667
TI - The curious case of cyberchondria: A longitudinal study on the reciprocal
relationship between health anxiety and online health information seeking.
AB - The current study is the first to longitudinally investigate the reciprocal
relationship between online health information seeking and health anxiety, i.e.,
cyberchondria. Expectations were that health anxious individuals who go online to
find health information, experience an increase in health anxiety, which in turn
will reinforce online seeking. A 4-wave longitudinal survey study among 5322
respondents aged 16-93 was conducted. Our results showed that individuals who are
more health anxious than others, search online for health information more.
Moreover, the results provided initial evidence for the expected reciprocal
relationship between health anxiety and online health information seeking in
respondents with non-clinical levels of health anxiety at the start of the study.
However, this reciprocal relationship could not be found in a subsample of
clinically health anxious individuals. Although for these individuals online
health information seeking did not seem to exacerbate health anxiety levels, it
might still serve as a maintaining factor of clinical health anxiety.
PMID- 27497666
TI - Different expression patterns of renal Na+/K+-ATPase alpha-isoform-like proteins
between tilapia and milkfish following salinity challenges.
AB - Euryhaline teleosts can survive in a broad range of salinity via alteration of
the molecular mechanisms in certain osmoregulatory organs, including in the gill
and kidney. Among these mechanisms, Na+/K+-ATPase (NKA) plays a crucial role in
triggering ion-transporting systems. The switch of NKA isoforms in euryhaline
fish gills substantially contributes to salinity adaptation. However, there is
little information about switches in the kidneys of euryhaline teleosts.
Therefore, the responses of the renal NKA alpha-isoform protein switch to
salinity challenge in euryhaline tilapia (Oreochromis mossambicus) and milkfish
(Chanos chanos) with different salinity preferences were examined and compared in
this study. Immunohistochemical staining in tilapia kidneys revealed the
localization of NKA in renal tubules rather than in the glomeruli, similar to our
previous findings in milkfish kidneys. Protein abundance in the renal NKA pan
alpha-subunit-like, alpha1-, and alpha3-isoform-like proteins in seawater
acclimated tilapia was significantly higher than in the freshwater group, whereas
the alpha2-isoform-like protein exhibited the opposite pattern of expression. In
the milkfish, higher protein abundance in the renal NKA pan alpha-subunit-like
and alpha1-isoform-like proteins was found in freshwater-acclimated fish, whereas
no difference was found in the protein abundance of alpha2- and alpha3-isoform
like proteins between groups. These findings suggested that switches for renal
NKA alpha-isoforms, especially the alpha1-isoform, were involved in renal
osmoregulatory mechanisms of euryhaline teleosts. Moreover, differences in
regulatory responses of the renal NKA alpha-subunit to salinity acclimation
between tilapia and milkfish revealed that divergent mechanisms for maintaining
osmotic balance might be employed by euryhaline teleosts with different salinity
preferences.
PMID- 27497668
TI - Effects of oxidative stress on hyperglycaemia-induced brain malformations in a
diabetes mouse model.
AB - Pregestational diabetes mellitus (PGDM) enhances the risk of fetal
neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced
neurodevelopmental defects is not fully understood. In this study, several
typical neurodevelopmental defects were identified in the streptozotocin-induced
diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1
labelled neuronal differentiation was suppressed and glial fibrillary acidic
protein-labelled glial cell lineage differentiation was slightly promoted in
pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose
did not change the U87 cell viability, but glial cell line-derived neurotrophic
factor expression was altered with varying glucose concentrations. Mouse maternal
hyperglycaemia significantly increased Tunel(+) apoptosis but did not
dramatically affect PCNA(+) cell proliferation in the process. To determine the
cause of increased apoptosis, we determined the SOD activity, the expression of
Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found
that all of them significantly increased in PGDM fetal brains compared with
controls. However, Nrf2 expression in U87 cells was not significantly changed by
different glucose concentrations. In mouse telencephalon, we observed the co
localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2
in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose
concentrations. Taken together, the data suggest that Nrf2-modulated antioxidant
stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental
defects.
PMID- 27497670
TI - Sulforaphane Prevents Neuronal Apoptosis and Memory Impairment in Diabetic Rats.
AB - BACKGROUND/AIMS: To explore the effects of sulforaphane (SFN) on neuronal
apoptosis in hippocampus and memory impairment in diabetic rats. METHODS: Thirty
male rats were randomly divided into normal control, diabetic model and SFN
treatment groups (N = 10 in each group). Streptozotocin (STZ) was applied to
establish diabetic model. Water Morris maze task was applied to test learning and
memory. Tunel assaying was used to detect apoptosis in hippocampus. The
expressions of Caspase-3 and myeloid cell leukemia 1(MCL-1) were detected by
western blotting. Neurotrophic factor levels and AKT/GSK3beta pathway were also
detected. RESULTS: Compared with normal control, learning and memory were
apparently impaired, with up-regulation of Caspase-3 and down-regulation of MCL-1
in diabetic rats. Apoptotic neurons were also found in CA1 region after diabetic
modeling. By contrast, SFN treatment prevented the memory impairment, decreased
the apoptosis of hippocampal neurons. SFN also attenuated the abnormal expression
of Caspase-3 and MCL-1 in diabetic model. Mechanically, SFN treatment reversed
diabetic modeling-induced decrease of p-Akt, p-GSK3beta, NGF and BDNF
expressions. CONCLUSION: SFN could prevent the memory impairment and apoptosis of
hippocampal neurons in diabetic rat. The possible mechanism was related to the
regulation of neurotropic factors and Akt/GSK3beta pathway.
PMID- 27497669
TI - LEFTY2 Controls Migration of Human Endometrial Cancer Cells via Focal Adhesion
Kinase Activity (FAK) and miRNA-200a.
AB - BACKGROUND: LEFTY2, a suppressor of cell proliferation, tumor growth, regulator
of stemness and embryonic differentiation, is a negative regulator of cancer cell
reprogramming. Malignant transformation may lead to migration requiring loss of
adhesion and gain of migratory activity. Signaling involved in the orchestration
of migration, proliferation and spreading of cells include focal adhesion kinase
(FAK) and adhesion molecule E-cadherin. AIMS: The present study explored whether
LEFTY2 influences the proliferation marker MKi67, FAK activity, E-cadherin
abundance and migration of Ishikawa human endometrial carcinoma cells. Moreover,
the study explored the involvement of microRNA-200a (miR-200a), which is known to
regulate cellular adhesion by targeting E-Cadherin. METHODS: FAK activity was
estimated from FAK phosphorylation quantified by Western blotting, migration
utilizing a wound healing assay, miR-200a and MKi67 expression levels utilizing
qRT-PCR, cell proliferation and apoptosis using BrdU and Annexin V staining,
respectively, and E-Cadherin (E-Cad) abundance, using confocal microscopy.
RESULTS: LEFTY2 (25 ng/ml, 48 hours) treatment was followed by decrease of MKi67
expression, FAK activity and migration. LEFTY2 upregulated miRNA-200a and E-Cad
protein level in Ishikawa cells. The effect of LEFTY2 on migration was mimicked
by FAK inhibitor PF 573228 (50 uM). Addition of LEFTY2 in the presence of PF
573228 did not result in a further significant decline of migration. CONCLUSION:
In conclusion, LEFTY2 down-regulates MKi67 expression and FAK activity, up
regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of
endometrial cell proliferation and migration.
PMID- 27497671
TI - N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs
after Perinatal Asphyxia.
AB - BACKGROUND: Perinatal asphyxia and ensuing reoxygenation change the antioxidant
capacity of cells and organs. OBJECTIVES: To analyze the neuroprotective effect
of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia
reoxygenation with an emphasis on proinflammatory cytokines and the transcription
factor NF-kappaB in the prefrontal cortex of neonatal pigs. METHODS: Twenty-nine
newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One
sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8%
oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure
fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5
h after hypoxia. Samples of prefrontal cortex and plasma were analyzed. RESULTS:
Cortex: there was no significant difference in mRNA expression between the
intervention groups regarding IL-1beta, IL6, TNFalpha, MMP2, MMP9 or IL18. Pigs
exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a
significantly lower protein concentration of IL-1beta than pigs treated with
saline (placebo controls), i.e. 8.8 +/- 3.9 versus 16.8 +/- 10.5 pg/mg protein (p
= 0.02). The activation of the transcription factor NF-kappaB (measured as the
fold-change of phosphorylated p65Ser 536), was reduced in the NACA-pigs when
compared to the placebo controls (5.2 +/- 4.3 vs. 16.0 +/- 13.5; p = 0.02). No
difference between the intervention groups regarding brain histopathology or in
the levels of 8-oxoguanine measured in the prefrontal cortex were observed.
Plasma: the NACA-pigs had a stronger reduction of TNFalpha in the first 30 min
following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24
(14-32)% (p = 0.01). CONCLUSION: The reduced levels of the pivotal inflammatory
markers IL-1beta and TNFalpha and the transcription factor NF-kappaB may indicate
that NACA has possible neuroprotective effects after perinatal asphyxia.
PMID- 27497672
TI - Pulmonary Function in Patients with End-Stage Renal Disease: Effects of
Hemodialysis and Fluid Overload.
AB - BACKGROUND Respiratory system disorders are one of the most prevalent
complications in end-stage renal disease patients on hemodialysis. However, the
pathogenesis of impaired pulmonary functions has not been completely elucidated
in these patients. We designed a study to investigate acute effects of
hemodialysis treatment on spirometry parameters, focusing on the relationship
between pulmonary function and fluid status in hemodialysis patients. MATERIAL
AND METHODS We enrolled 54 hemodialysis patients in this study. Multifrequency
bioimpedance analysis (BIA) was used to assess fluid status before and 30 min
after the midweek of hemodialysis (HD). Overhydration (OH)/extracellular water
(ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined
as OH/ECW >=7%. Spirometry was performed before and after hemodialysis. RESULTS
Forced vital capacity (FVC), FVC%, and forced expiratory volume in the first
second (FEV1) levels were significantly increased after hemodialysis. FVC, FVC%,
FEV1, FEV1%, mean forced expiratory flow between 25% and 75% of the FVC (FEF25
75), FEF25-75%, peak expiratory flow rate (PEFR), and PEFR% were significantly
lower in patients with fluid overload than in those without. OH/ECW ratio was
negatively correlated with FVC, FVC%, FEV1, FEV1%, FEF25-75, FEF25-75%, PEFR, and
PEFR%. Stepwise multiple regression analysis revealed that male sex and increased
ultrafiltration volume were independently associated with higher FVC, whereas
increased age and OH/ECW ratio were independently associated with lower FVC.
CONCLUSIONS Fluid overload is closely associated with restrictive and obstructive
respiratory abnormalities in HD patients. In addition, hemodialysis has a
beneficial effect on pulmonary function tests, which may be due to reduction of
volume overload.
PMID- 27497674
TI - Variability in source sediment contributions by applying different statistic test
for a Pyrenean catchment.
AB - Information on sediment contribution and transport dynamics from the contributing
catchments is needed to develop management plans to tackle environmental problems
related with effects of fine sediment as reservoir siltation. In this respect,
the fingerprinting technique is an indirect technique known to be valuable and
effective for sediment source identification in river catchments. Large
variability in sediment delivery was found in previous studies in the Barasona
catchment (1509 km2, Central Spanish Pyrenees). Simulation results with SWAT and
fingerprinting approaches identified badlands and agricultural uses as the main
contributors to sediment supply in the reservoir. In this study the <63 MUm
sediment fraction from the surface reservoir sediments (2 cm) are investigated
following the fingerprinting procedure to assess how the use of different
statistical procedures affects the amounts of source contributions. Three optimum
composite fingerprints were selected to discriminate between source contributions
based in land uses/land covers from the same dataset by the application of (1)
discriminant function analysis; and its combination (as second step) with (2)
Kruskal-Wallis H-test and (3) principal components analysis. Source contribution
results were different between assessed options with the greatest differences
observed for option using #3, including the two step process: principal
components analysis and discriminant function analysis. The characteristics of
the solutions by the applied mixing model and the conceptual understanding of the
catchment showed that the most reliable solution was achieved using #2, the two
step process of Kruskal-Wallis H-test and discriminant function analysis. The
assessment showed the importance of the statistical procedure used to define the
optimum composite fingerprint for sediment fingerprinting applications.
PMID- 27497673
TI - Geographic Discordance Between Patient Residence and Incident Location in
Emergency Medical Services Responses.
AB - STUDY OBJECTIVE: The location of a patient's residence is often used for
emergency medical services (EMS) system planning. Our objective is to evaluate
the association between patient residence and emergency incident zip codes for
911 calls. METHODS: We used data from the 2013 National Emergency Medical
Services Information System (NEMSIS) Public-Release Research Dataset. We studied
all 911 calls with a valid complaint by dispatch, identifying zip codes for both
the residence and incident locations (n=12,376,784). The primary outcomes were
geographic and distance discordances between patient residence and incident zip
codes. We used a multivariate logistic regression model to determine geographic
discordance between residence and incident zip codes by dispatch complaint, age,
and sex. We also measured distances between locations with geospatial processing.
RESULTS: The overall proportion of geographic discordance for all 911 calls was
27.7% (95% confidence interval [CI] 27.7% to 27.8%) and the median distance
discordance was 11.5 miles (95% CI 11.5 to 11.5 miles). Lower geographic
discordance rates were found among patients aged 65 to 79 years (20.2%; 95% CI
20.1% to 20.2%) and 80 years and older (14.5%; 95% CI 14.5% to 14.6%). Motor
vehicle crashes (63.5%; 95% CI 63.5% to 63.6%), industrial accidents (59.3%; 95%
CI 58.0% to 60.6%), and mass casualty incidents (50.6%; 95% CI 49.6% to 51.5%)
were more likely to occur outside a patient's residence zip code. Median network
distance between home and incident zip centroid codes ranged from 8.6 to 23.5
miles. CONCLUSION: In NEMSIS, there was geographic discordance between patient
residence zip code and call location zip code in slightly more than one quarter
of EMS responses records. The geographic discordance rates between residence and
incident zip codes were associated with dispatch complaints and age. Although a
patient's residence might be a valid proxy for incident location for elderly
patients, this relationship holds less true for other age groups and among
different complaints. Our findings have important implications for EMS system
planning, resource allocation, and injury surveillance.
PMID- 27497675
TI - Early decision framework for integrating sustainable risk management for complex
remediation sites: Drivers, barriers, and performance metrics.
AB - As the environmental remediation industry matures, remaining sites often have
significant underlying technical challenges and financial constraints. More often
than not, significant remediation efforts at these "complex" sites have not
achieved stringent, promulgated cleanup goals. Decisions then have to be made
about whether and how to commit additional resources towards achieving those
goals, which are often not achievable nor required to protect receptors. Guidance
on cleanup approaches focused on evaluating and managing site-specific conditions
and risks, rather than uniformly meeting contaminant cleanup criteria in all
media, is available to aid in this decision. Although these risk-based cleanup
approaches, such as alternative endpoints and adaptive management strategies,
have been developed, they are under-utilized due to environmental, socio
economic, and risk perception barriers. Also, these approaches are usually
implemented late in the project life cycle after unsuccessful remedial attempts
to achieve stringent cleanup criteria. In this article, we address these barriers
by developing an early decision framework to identify if site characteristics
support sustainable risk management, and develop performance metrics and tools to
evaluate and implement successful risk-based cleanup approaches. In addition, we
address uncertainty and risk perception challenges by aligning risk-based cleanup
approaches with the concepts of risk management and sustainable remediation. This
approach was developed in the context of lessons learned from implementing
remediation at complex sites, but as a framework can, and should, be applied to
all sites undergoing remediation.
PMID- 27497676
TI - A 3D Toolbox to Enhance Physiological Relevance of Human Tissue Models.
AB - We discuss the current challenges and future prospects of flow-based organoid
models and 3D self-assembling scaffolds. The existing paradigm of 3D culture
suffers from a lack of control over organoid size and shape; can be an obstacle
for cell harvesting and extended cellular and molecular analysis; and does not
provide access to the function of exocrine glands. Moreover, existing organ-on
chip models are mostly composed of 2D extracellular matrix (ECM)-coated
elastomeric membranes that do not mimic real organ architectures. A new
comprehensive 3D toolbox for cell biology has emerged to address some of these
issues. Advances in microfabrication and cell-culturing approaches enable the
engineering of sophisticated models that mimic organ 3D architectures and
physiological conditions, while supporting flow-based drug screening and
secretomics-based diagnosis.
PMID- 27497677
TI - The role of anxiety sensitivity in the relation between anxious arousal and
cannabis and alcohol use problems among low-income inner city racial/ethnic
minorities.
AB - The current study explored anxiety sensitivity as a factor accounting for the
association between anxious arousal and problems related to use of cannabis and
alcohol among a health disparity sample (low income minorities). Specifically,
participants were 130 low-income racial/ethnic minorities who reported daily
cannabis use (Mage=37.7 SD=10.0; 28.5% female). There were significant indirect
associations of anxious arousal via anxiety sensitivity in relation to: cannabis
use problems, cannabis withdrawal symptoms, use of cannabis to cope, as well as
hazardous drinking, alcohol use problems, and alcohol consumption. These data
indicate anxiety sensitivity is a possible mechanism underlying the relation
between anxious arousal and substance use problems among low-income racial/ethnic
minorities. Future work could evaluate the efficacy of cannabis and alcohol use
treatments incorporating anxiety sensitivity reduction techniques to facilitate
amelioration of anxiety and substance use and offset mental health inequalities
for this population.
PMID- 27497678
TI - Prevalence of autism spectrum disorders in a semiurban community in south India.
PMID- 27497680
TI - Associations of blood heavy metal levels with intraocular pressure.
AB - PURPOSE: Whether or which blood heavy metal levels (BHMLs) influence elevating
intraocular pressure (IOP) are unknown. We examined the relationship among blood
lead, mercury, and cadmium levels, blood pressure (BP), and IOP and assessed
whether BP mediates these BHMLs-IOP associations. METHODS: We analyzed data on
8371 adult (>=20 years) from the Korea National Health and Nutrition Examination
Survey from 2008 to 2012. Mediation analysis was used to examine the contribution
of BP to the BHMLs-IOP relationship. RESULTS: IOP and three BHMLs were
significantly associated with systolic and diastolic BP. But IOP was associated
with only blood lead and mercury levels. BP significantly mediated lead-IOP and
mercury-IOP associations: BP accounted for 20.5% and 14.2% of the association
with IOP. Blood lead and mercury levels were significantly associated with IOP.
CONCLUSIONS: BP significantly mediates the effects of those blood lead and
mercury levels on IOP outcome. Prospective studies are needed to further examine
the causal pathway from BHMLs to IOP elevation.
PMID- 27497679
TI - Early life growth, socioeconomic status, and mammographic breast density in an
urban US birth cohort.
AB - PURPOSE: Rapid infant and childhood growth has been associated with chronic
disease later in life, including breast cancer. Early life socioeconomic status
(SES) influences childhood growth, but few studies have prospective measures from
birth to consider the effects of early life growth and SES on breast cancer risk.
METHODS: We used prospectively measured early life SES and growth (percentile
weight change in height and weight between each pair of consecutive time points
at birth, 4 months, 1 and 7 years). We performed linear regression models to
obtain standardized estimates of the association between 1 standard deviation
increase in early life SES and growth and adult mammographic density (MD), a
strong risk factor for breast cancer, in a diverse birth cohort (n = 151; 37%
white, 38% black, 25% Puerto Rican; average age at mammogram = 42.4). RESULTS: In
models adjusted for race/ethnicity, prenatal factors, birthweight, infant and
childhood growth, and adult body mass index, percentile weight change from 1 year
to 7 years was inversely associated with percent MD (standardized coefficient
(Stdbeta) = -0.28, 95% CI: -0.55 to -0.01), and higher early life SES was
positively associated with percent MD (Stdbeta = 0.24, 95% CI: 0.04-0.43).
Similar associations were observed for dense area, but those estimates were not
statistically significant. CONCLUSIONS: These results suggest opposite and
independent effects of early life SES and growth on MD.
PMID- 27497681
TI - Potential Role of Aminoprocalcitonin in the Pathogenesis of Alzheimer Disease.
AB - Increasing evidence suggests that inflammatory responses cause brain atrophy and
play a prominent and early role in the progression of Alzheimer disease. Recent
findings show that the neuroendocrine peptide aminoprocalcitonin (NPCT) plays a
critical role in the development of systemic inflammatory response; however, the
presence, possible function, regulation, and mechanisms by which NPCT may be
involved in Alzheimer disease neuropathology remain unknown. We explored the
expression of NPCT and its interaction with amyloid-beta (Abeta), and
proinflammatory and neurogenic effects. By using brain samples of Alzheimer
disease patients and APP/PS1 transgenic mice, we evaluated the potential role of
NPCT on Abeta-related pathology. We found that NPCT is expressed in hippocampal
and cortical neurons and Abeta-induced up-regulation of NPCT expression.
Peripherally administered antibodies against NPCT decreased microglial
activation, decreased circulating levels of proinflammatory cytokines, and
prevented Abeta-induced neurotoxicity in experimental models of Alzheimer
disease. Remarkably, anti-NPTC therapy resulted in a significant improvement in
the behavioral status of APP/PS1 mice. Our results indicate a central role of
NPCT in Alzheimer disease pathogenesis and suggest NPCT as a potential biomarker
and therapeutic target.
PMID- 27497682
TI - The Wellness Theorem: A Test of the Hypothesis.
PMID- 27497683
TI - Reactions to Rituximab in an Outpatient Infusion Center: A 5-Year Review.
AB - BACKGROUND: Reactions to rituximab occur frequently, with up to 77% of patients
developing a reaction during initial exposure. The safety of rechallenging
patients after a reaction is not clear and standard guidelines are lacking.
OBJECTIVE: To better understand clinical decision making surrounding rituximab
reactions and subsequent rechallenge. METHODS: We performed a 5-year
retrospective review of all rituximab reactions at a large academic outpatient
infusion center. Patients' demographic characteristics, clinical symptoms, and
management of reactions were reviewed. Reaction severity was classified using
standard criteria. RESULTS: Between June 2006 and January 2011, 67 patients (mean
age, 58 +/- 13 years, 54% men) with at least 1 rituximab reaction were
identified. Most reactions occurred during the first exposure to rituximab (63%).
Most reactions (n = 59 [88%]) were grade 1 or 2. Fifty-one patients (n = 51
[88%]) were rechallenged with rituximab on the same day as the initial reaction.
Most patients with a grade 1 reaction tolerated rechallenge. Conversely, all 4
patients with a grade 3 reaction had a reaction during rechallenge. The outcome
of same-day rechallenge after an initial grade 2 reaction was varied; most
patients (26 of 31 [84%]) tolerated same-day challenge, but 5 patients had a
reaction (all grade 1-2 severity). CONCLUSIONS: Consistent with previous data,
our observations suggest that patients who experience grade 1 reactions to
rituximab can be safely rechallenged the same day. A grade 3 or 4 reaction should
prompt referral to an allergy specialist for risk assessment before additional
rituximab administration. Further research is needed to understand the optimal
management of patients with grade 2 reactions.
PMID- 27497684
TI - Serum levels of copeptin are associated with type 2 diabetes and diabetic
complications in Chinese population.
AB - PURPOSE: The aim of this study was to investigate copeptin levels in serum, and
assess their associations with type 2 diabetes (T2DM) and diabetic complications.
METHODS: In this post hoc analysis, serum levels of copeptin were tested in 306
patients with T2DM. Clinical information including diabetic retinopathy (DR) and
diabetic nephropathy (DN) were collected. The relation of serum copeptin with DR
and DN were investigated with the use of logistic regression models according to
equal quartiles of the distributions of serum copeptin. RESULTS: We found that
serum copeptin levels were significantly higher in diabetes as compared to normal
controls [9.4(IQR, 7.4-12.5) pmol/L vs. 4.1(IQR, 2.5-6.2) pmol/L; P<0.0001]. In
multivariate analysis, there was an increased risk of T2DM associated with
copeptin levels (OR 1.312, 95% CI: 1.204-1.403; P<0.0001) after adjusting for
possible confounders. After adjustment for possible confounders, serum copeptin
levels were positively associated with the DR (odds ratio [OR], 1.117; 95%
confidence interval [CI], 1.072-1.241; P<0.001) and DN (OR, 1.259; 95% CI, 1.198
1.323; P<0.001). Compared with the first quartile of serum copeptin levels, the
ORs for DR and DN were as follows: second quartile, 1.19 (95% CI, 0.94-1.51,
P=0.12) and 1.37 (95% CI, 0.78-2.37, P=0.28); third quartile, 1.61 (95% CI, 1.18
2.43, P=0.005) and 2.12 (95% CI, 1.32-3.27, P=0.003); fourth quartile, 2.83 (95%
CI, 2.04-4.93; P<0.001) and 3.48 (95% CI, 1.77-7.03; P<0.001), respectively.
CONCLUSIONS: Using a post-hoc analysis our data show that elevated serum levels
of copeptin are associated with type 2 diabetes and diabetic complications in
Chinese population, suggesting a potential role of the AVP system (copeptin) in
the pathophysiology of diabetes.
PMID- 27497686
TI - Trivalent chromium alleviates oleic acid induced steatosis in SMMC-7721 cells by
decreasing fatty acid uptake and triglyceride synthesis.
AB - Trivalent chromium [Cr(III)] has been shown as an essential trace element for
human health. Previous studies depict that Cr(III) plays important roles in
maintaining normal glucose and lipid metabolism, whereas its effect on the
hepatic lipid metabolism is still unknown. In the present study, we investigated
the effects and underlying mechanisms of Cr on hepatic steatosis induced by oleic
acid (OA) in human hepatoma SMMC-7721 cells. Hepatic steatosis model was co
administered with Cr. Indexes of lipid accumulation were determined and
associated genes expression were analyzed. The data showed that OA could induce
lipid accumulation and triglyceride (TG) content in SMMC-7721 cells, and
significantly increase the expression of cluster of differentiation 36 (CD36) and
diacylglycerol acyltransferase 2 (DGAT2). This steatosis effect of OA was
ameliorated by Cr. The TG accumulation and up-regulation of CD36 and DGAT2 genes
followed steatosis induction were inhibited by Cr. After the treatment of Cr,
excessive intracellular OA content was also attenuated. Furthermore, Cr still
performed inhibitory effect of DGAT2 expression at the presence of DGAT2 agonist
or inhibitor, which indicated that the inhibitory effect of Cr on lipogenesis is
associated with the downregulation of DGAT2 expression. These findings
demonstrate that Cr alleviates hepatic steatosis via suppressing CD36 expression
to prevent fatty acid uptake, as well as suppressing DGAT2 expression to inhibit
TG synthesis. It suggests that CD36 and DGAT2 might become the novel drug targets
for their properties in hepatic steatosis. Most importantly, Cr may be a
potential anti-steatosis candidate to offer protective effects against liver
damage.
PMID- 27497685
TI - Diabetes and increased lipid peroxidation are associated with systemic
inflammation even in well-controlled patients.
AB - BACKGROUND: The effect of the interaction between type 2 diabetes and
dyslipidemia on inflammation and lipid peroxidation (LPO) has not been assessed.
AIM: To investigate whether diabetes coupled with dyslipidemia alters oxidative
metabolism leading to increased LPO products and inflammatory status. METHODS:
100 patients were divided into four groups based upon diabetic and dyslipidemic
status: poorly controlled diabetes with dyslipidemia (DM-PC/D), well-controlled
diabetes with dyslipidemia (DM-WC/D), normoglycemic individuals with dyslipidemia
(NG/D), and normoglycemic individuals without dyslipidemia (NG/ND). Plasma was
evaluated for an LPO product (MDA), antioxidant levels and inflammatory
cytokines. RESULTS: Diabetics presented significantly higher levels of LPO
(p<0.05) and the DM-PC/D had higher levels of proinflammatory cytokines and MDA
in the plasma in comparison with normoglycemics (p<0.05). Interestingly IL1-beta,
IL-6, and TNF-alpha in DM-WC/D were not statistically different from those in DM
PC/D. Normoglycemic individuals with dyslipidemia presented significantly
increased levels of IL-6 and TNF-alpha when compared to normoglycemic without
dyslipidemia (p<0.05). MDA levels were also positively correlated with the
presence of DM complications (r=0.42, p<0.01). CONCLUSIONS: These findings show
that dyslipidemia is associated with an increased inflammatory status, even in
well-controlled diabetics and in normoglycemics. Our results suggest that lipid
metabolism and peroxidation are important for the development of inflammation,
which is elevated in several complications associated with diabetes.
PMID- 27497687
TI - New gold carbene complexes as candidate anticancer agents.
AB - Three structurally related gold(I) carbene complexes with bulky hydrophobic
ligands i.e. 1-3 were investigated in solution for further consideration as
candidate anticancer agents. Cytotoxic assays were subsequently conducted on bone
marrow-derived preosteoclast cell line of human origin (FLG 29.1) and human colon
cancer cells (HCT-116). A far greater cytotoxic activity was measured for
compound 1 against HCT-116 cells compared to 2 and 3; conversely, all compounds
were highly and similarly active against FLG 29.1 cells. Results obtained for the
reaction of complexes 1 and 2 with RNase A documented the occurrence of a weak
interaction with this model protein and the formation of a tiny amount of the
corresponding adduct. Moreover, a certain reactivity of the complex 2 was also
detected toward GSH. The general implications of the obtained results are
discussed.
PMID- 27497689
TI - An Extended Loop of the Pup Ligase, PafA, Mediates Interaction with Protein
Targets.
AB - Pupylation, the bacterial equivalent of ubiquitylation, involves the conjugation
of a prokaryotic ubiquitin-like protein (Pup) to protein targets. In contrast to
the ubiquitin system, where many ubiquitin ligases exist, a single bacterial
ligase, PafA, catalyzes the conjugation of Pup to a wide array of protein
targets. As mediators of target recognition by PafA have not been identified, it
would appear that PafA alone determines pupylation target selection. Previous
studies indicated that broad specificity and promiscuity are indeed inherent PafA
characteristics that probably dictate which proteins are selected for degradation
by the Pup-proteasome system. Nonetheless, despite the canonical role played by
PafA in the Pup-proteasome system, the molecular mechanism that dictates target
binding by PafA remains uncharacterized since the discovery of this enzyme about
a decade ago. In this study, we report the identification of PafA residues
involved in the binding of protein targets. Initially, docking analysis predicted
the residues on PafA with high potential for target binding. Mutational and
biochemical approaches subsequently confirmed these predictions and identified a
series of additional residues located on an extended loop at the edge of the PafA
active site. Mutating residues in this loop rendered PafA defective in the
pupylation of a wide variety of protein targets but not in its catalytic
mechanism, suggesting an important role for this extended loop in the binding of
protein targets. As such, these findings pave the way toward an understanding of
the molecular determinants that dictate the broad substrate specificity of PafA.
PMID- 27497688
TI - Dimerization Controls Marburg Virus VP24-dependent Modulation of Host
Antioxidative Stress Responses.
AB - Marburg virus (MARV), a member of the Filoviridae family that also includes Ebola
virus (EBOV), causes lethal hemorrhagic fever with case fatality rates that have
exceeded 50% in some outbreaks. Within an infected cell, there are numerous host
viral interactions that contribute to the outcome of infection. Recent studies
identified MARV protein 24 (mVP24) as a modulator of the host antioxidative
responses, but the molecular mechanism remains unclear. Using a combination of
biochemical and mass spectrometry studies, we show that mVP24 is a dimer in
solution that directly binds to the Kelch domain of Kelch-like ECH-associated
protein 1 (Keap1) to regulate nuclear factor (erythroid-derived 2)-like 2 (Nrf2).
This interaction between Keap1 and mVP24 occurs through the Kelch interaction
loop (K-Loop) of mVP24 leading to upregulation of antioxidant response element
transcription, which is distinct from other Kelch binders that regulate Nrf2
activity. N-terminal truncations disrupt mVP24 dimerization, allowing monomeric
mVP24 to bind Kelch with higher affinity and stimulate higher antioxidative
stress response element (ARE) reporter activity. Mass spectrometry-based mapping
of the interface revealed overlapping binding sites on Kelch for mVP24 and the
Nrf2 proteins. Substitution of conserved cysteines, C209 and C210, to alanine in
the mVP24 K-Loop abrogates Kelch binding and ARE activation. Our studies identify
a shift in the monomer-dimer equilibrium of MARV VP24, driven by its interaction
with Keap1 Kelch domain, as a critical determinant that modulates host responses
to pathogenic Marburg viral infections.
PMID- 27497690
TI - Substrates and physiological functions of secretase rhomboid proteases.
AB - Rhomboids are conserved intramembrane serine proteases with widespread functions.
They were the earliest discovered members of the wider rhomboid-like superfamily
of proteases and pseudoproteases. The secretase class of rhomboid proteases,
distributed through the secretory pathway, are the most numerous in eukaryotes,
but our knowledge of them is limited. Here we aim to summarise all that has been
published on secretase rhomboids in a concise encyclopaedia of the enzymes, their
substrates, and their biological roles. We also discuss emerging themes of how
these important enzymes are regulated.
PMID- 27497691
TI - Predicting the 5-Year Risk of Biochemical Relapse After Postprostatectomy
Radiation Therapy in >=PT2, pN0 Patients With a Comprehensive Tumor Control
Probability Model.
AB - PURPOSE: To fit the individual biochemical recurrence-free survival (bRFS) data
from patients treated with postprostatectomy radiation therapy (RT) with a
comprehensive tumor control probability (TCP) model. METHODS AND MATERIALS:
Considering pre-RT prostate-specific antigen (PSA) as a surrogate of the number
of clonogens, bRFS may be expressed as a function of dose-per-fraction-dependent
radiosensitivity (alphaeff), the number of clonogens for pre-RT PSA = 1 ng/mL
(C), and the fraction of patients who relapse because of clonogens outside the
treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA
and Gleason score (GS). Data from 894 node-negative, >=pT2, pN0 hormone-naive
patients treated with adjuvant (n=331) or salvage (n=563) intent were available:
5-year bRFS data were fitted grouping patients according to GS (<7:392, =7:383,
>7:119). RESULTS: The median follow-up time, pre-RT PSA, and dose were 72 months,
0.25 ng/mL, and 66.6 Gy (range 59.4-77.4 Gy), respectively. The best-fit values
were 0.23 to 0.26 Gy(-1) and 10(7) for alphaeff and C for the model considering a
linear dependence between K and PSA. Calibration plots showed good agreement
between expected and observed incidences (slope: 0.90-0.93) and moderately high
discriminative power (area under the curve [AUC]: 0.68-0.69). Cross-validation
showed satisfactory results (average AUCs in the training/validation groups: 0.66
0.70). The resulting dose-effect curves strongly depend on pre-RT PSA and GS.
bRFS rapidly decreases with PSA: the maximum obtainable bRFS (defined as 95% of
the maximum) declined by about 2.7% and 4.5% for each increment of 0.1 ng/mL for
GS <7 and >=7, respectively. CONCLUSIONS: Individual data were fitted by a TCP
model, and the resulting best-fit parameters were radiobiologically consistent.
The model suggests that relapses frequently result from clonogens outside the
irradiated volume, supporting the choice of lymph-node irradiation, systemic
therapy, or both for specific subgroups (GS <7: PSA >0.8-1.0 ng/mL; GS >=7: PSA
>0.3 ng/mL). Early RT should be preferred over delayed RT; the detrimental effect
of PSA increase can never be fully compensated by increasing the dose, especially
for patients with GS >=7.
PMID- 27497692
TI - Y-family DNA polymerase-independent gap-filling translesion synthesis across
aristolochic acid-derived adenine adducts in mouse cells.
AB - Translesion DNA synthesis (TLS) operates when replicative polymerases are blocked
by DNA lesions. To investigate the mechanism of mammalian TLS, we employed a
plasmid bearing a single 7-(deoxyadenosine-N6-yl)-aristolactam I (dA-AL-I)
adduct, which is generated by the human carcinogen, aristolochic acid I, and
genetically engineered mouse embryonic fibroblasts. This lesion induces A to T
transversions at a high frequency. The simultaneous knockouts of the Polh, Poli
and Polk genes did not influence the TLS efficiency or the coding property of dA
AL-I, indicating that an unknown DNA polymerase(s) can efficiently catalyze the
insertion of a nucleotide opposite the adduct and subsequent extension.
Similarly, knockout of the Rev1 gene did not significantly affect TLS. However,
knockout of the Rev3l gene, coding for the catalytic subunit of polzeta,
drastically suppressed TLS and abolished dA-AL-I to T transversions. The results
support the idea that Rev1 is not essential for the cellular TLS functions of
polzeta in mammalian cells. Furthermore, the frequency of dA-AL-I to T
transversion was affected by a sequence context, suggesting that TLS, at least in
part, contributes to the formation of mutational hot and cold spots observed in
aristolochic acid-induced cancers.
PMID- 27497694
TI - Standardization of administered activities in paediatric nuclear medicine: the
EANM perspective.
PMID- 27497693
TI - Anatomic validation of the lateral malleolus as a cutaneous marker for the distal
insertion of the calcaneofibular ligament.
AB - PURPOSE: An anatomic study was performed to confirm whether the lateral malleolus
could serve as a simple and reproducible anatomic reference for the distal
insertion of the calcaneofibular ligament (CFL). METHODS: Dissection was
performed after placement of a Kirschner wire to simulate the calcaneal tunnel
for the distal insertion of the CFL. The skin was penetrated 1 cm distal and
posterior to the tip of the lateral malleolus. The main information recorded was
the distance from the Kirschner wire to the centre of the distal insertion of the
CFL. Other elements were noted (characteristics of the CFL, distance between the
distal insertion of the CFL-peroneal tubercle, nerve or tendon injuries).
RESULTS: Thirty ankles were dissected. The mean distance from the Kirschner wire
to the centre of the distal insertion of the CFL was 2.4 +/- 1.8 mm. Only one
case of peroneal injury was noted. The sural nerve was usually located a mean 1.8
+/- 1.1 mm from the Kirschner wire. The posterior tibial vascular pedicle was a
mean 27.8 +/- 3.5 mm from the point of exit of the Kirschner wire. CONCLUSION:
Using the lateral malleolus as the cutaneous reference for the distal insertion
of the CFL seems to be more reliable than the pure arthroscopic technique. This
study describes a percutaneous technique to obtain a calcaneal tunnel for distal
insertion of the CFL. The sural nerve is at the greatest risk of injury with this
technique and requires careful subcutaneous incision to prevent injury. This new
percutaneous technique is less invasive than a purely arthroscopic technique and
more accurately identifies the location of the tunnel. It can be used to do
calcaneal tunnel in clinical practice during anatomic ligament reconstruction for
chronic ankle instability.
PMID- 27497695
TI - Orthorexia nervosa by proxy?
PMID- 27497697
TI - Cross-cultural validation of the ICOAP and physical function short forms of the
HOOS and KOOS in a multi-country study of patients with hip and knee
osteoarthritis.
AB - OBJECTIVE: To evaluate the internal consistency and construct validity of the
Physical Function short-forms for the Hip and Knee Injury Osteoarthritis Outcome
Scores (HOOS-PS/KOOS-PS) and the Intermittent and Constant Osteoarthritis Pain
(ICOAP) in a nine country study of patients consulting for total hip or knee
replacement (THR or TKR). METHODS: Patients completed HOOS-PS or KOOS-PS, ICOAP
and Western Ontario and McMaster Universities' Osteoarthritis Index (WOMAC) pain
and physical function subscales at their consultation visit. Internal consistency
was calculated using Cronbach's alpha. The association of HOOS-PS/KOOS-PS and
ICOAP with WOMAC pain and function subscales was calculated with Spearman
correlation coefficients with 95% confidence intervals. RESULTS: HOOS-PS/KOOS-PS
and ICOAP demonstrated high internal consistency across countries (alpha 0.75
0.96 (hip) and 0.76-0.95 (knee)). Both HOOS-PS and KOOS-PS demonstrated high
correlations (0.76-0.90 and 0.75-0.91, respectively) with WOMAC function in all
countries. ICOAP exhibited moderate to high correlations with WOMAC pain and
function subscales (0.53-0.84 (hip) and 0.43-0.84 (knee)). CONCLUSION: The
psychometric properties of the HOOS-PS/KOOS-PS, and ICOAP were maintained across
all countries.
PMID- 27497698
TI - Simulation as an ethical imperative and epistemic responsibility for the
implementation of medical guidelines in health care.
AB - Guidelines orient best practices in medicine, yet, in health care, many real
world constraints limit their optimal realization. Since guideline implementation
problems are not systematically anticipated, they will be discovered only post
facto, in a learning curve period, while the already implemented guideline is
tweaked, debugged and adapted. This learning process comes with costs to human
health and quality of life. Despite such predictable hazard, the study and
modeling of medical guideline implementation is still seldom pursued. In this
article we argue that to systematically identify, predict and prevent medical
guideline implementation errors is both an epistemic responsibility and an
ethical imperative in health care, in order to properly provide beneficence,
minimize or avoid harm, show respect for persons, and administer justice.
Furthermore, we suggest that implementation knowledge is best achieved
technically by providing simulation modeling studies to anticipate the
realization of medical guidelines, in multiple contexts, with system and scenario
analysis, in its alignment with the emerging field of implementation science and
in recognition of learning health systems. It follows from both claims that it is
an ethical imperative and an epistemic responsibility to simulate medical
guidelines in context to minimize (avoidable) harm in health care, before
guideline implementation.
PMID- 27497696
TI - Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and
oxidants.
AB - The Kelch-like ECH associated protein 1 (Keap1) is a component of a Cullin3-based
Cullin-RING E3 ubiquitin ligase (CRL) multisubunit protein complex. Within the
CRL, homodimeric Keap1 functions as the Cullin3 adaptor, and importantly, it is
also the critical component of the E3 ligase that performs the substrate
recognition. The best-characterized substrate of Keap1 is transcription factor NF
E2 p45-related factor 2 (Nrf2), which orchestrates an elaborate transcriptional
program in response to environmental challenges caused by oxidants, electrophiles
and pro-inflammatory agents, allowing adaptation and survival under stress
conditions. Keap1 is equipped with reactive cysteine residues that act as sensors
for endogenously produced and exogenously encountered small molecules (termed
inducers), which have a characteristic chemical signature, reactivity with
sulfhydryl groups. Inducers modify the cysteine sensors of Keap1 and impair its
ability to target Nrf2 for ubiquitination and degradation. Consequently, Nrf2
accumulates, enters the nucleus and drives the transcription of its target genes,
which encode a large network of cytoprotective proteins. Here we summarize the
early studies leading to the prediction of the existence of Keap1, followed by
the discovery of Keap1 as the main negative regulator of Nrf2. We then describe
the available structural information on Keap1, its assembly with Cullin3, and its
interaction with Nrf2. We also discuss the multiple cysteine sensors of Keap1
that allow for detection of a wide range of endogenous and environmental
inducers, and provide fine-tuning and tight control of the Keap1/Nrf2 stress
sensing response.
PMID- 27497699
TI - Overexpression of tropomyosin receptor kinase A improves the survival and Schwann
like cell differentiation of bone marrow stromal cells in nerve grafts for
bridging rat sciatic nerve defects.
AB - BACKGROUND AIMS: Bone marrow stromal cells (BMSCs) can differentiate into Schwann
like cells in vivo and effectively promote nerve regeneration and functional
recovery as the seed cells for peripheral nerve repair. However, the survival
rate and neural differentiation rate of the transplanted BMSCs are very low,
which would limit their efficacy. METHODS: In this work, rat BMSCs were infected
by recombinant lentiviruses to construct tropomyosin receptor kinase A (TrkA)
overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then used in
transplantation for rat sciatic nerve defects. RESULTS: We showed that lentivirus
mediated overexpression of TrkA in BMSCs can promote cell survival and protect
against serum-starve-induced apoptosis in vitro. At 8 weeks after
transplantation, the Schwann-like differentiated ratio of the existing implanted
cells had reached 74.8 +/- 1.6% in TrkA-overexpressing BMSCs-laden nerve grafts,
while 40.7 +/- 2.3% and 42.3 +/- 1.5% in vector and control BMSCs-laden nerve
grafts, but only 8.2 +/- 1.8% in TrkA-shRNA-expressing BMSCs-laden nerve grafts.
The cell apoptosis ratio of the existing implanted cells in TrkA-overexpressing
BMSCs-laden nerve grafts was 16.5 +/- 1.2%, while 33.9 +/- 1.9% and 42.6 +/- 2.9%
in vector and control BMSCs-laden nerve grafts, but 87.2 +/- 2.5% in TrkA-shRNA
expressing BMSCs-laden nerve grafts. CONCLUSIONS: These results demonstrate that
TrkA overexpression can improve the survival and Schwann-like cell
differentiation of BMSCs and prevent cell death in nerve grafts, which may have
potential implication in advancing cell transplantation for peripheral nerve
repair.
PMID- 27497700
TI - A robust, good manufacturing practice-compliant, clinical-scale procedure to
generate regulatory T cells from patients with amyotrophic lateral sclerosis for
adoptive cell therapy.
AB - Regulatory T cells (Tregs) play a fundamental role in the maintenance of self
tolerance and immune homeostasis. Defects in Treg function and/or frequencies
have been reported in multiple disease models. Amyotrophic lateral sclerosis
(ALS) is a progressive neurodegenerative disorder affecting upper and lower motor
neurons. Compelling evidence supports a neuroprotective role for Tregs in this
disease. Indeed, rapid progression in ALS patients is associated with decreased
FoxP3 expression and Treg frequencies. Thus, we propose that strategies to
restore Treg number and function may slow disease progression in ALS. In this
study, we developed a robust, Good Manufacturing Practice (GMP)-compliant
procedure to enrich and expand Tregs from ALS patients. Tregs isolated from these
patients were phenotypically similar to those from healthy individuals but were
impaired in their ability to suppress T-cell effector function. In vitro
expansion of Tregs for 4 weeks in the presence of GMP-grade anti-CD3/CD28 beads,
interleukin (IL)-2 and rapamcyin resulted in a 25- to 200-fold increase in their
number and restored their immunoregulatory activity. Collectively, our data
facilitate and support the implementation of clinical trials of adoptive therapy
with ex vivo expanded and highly suppressive Tregs in patients with ALS.
PMID- 27497701
TI - Expanded and armed natural killer cells for cancer treatment.
AB - The capacity of natural killer (NK) cells to recognize and kill transformed cells
suggests that their infusion could be used to treat cancer. It is difficult to
obtain large numbers of NK cells ex vivo by exposure to cytokines alone but the
addition of stimulatory cells to the cultures can induce NK cell proliferation
and long-term expansion. Some of these methods have been validated for clinical
grade application and support clinical trials testing feasibility and safety of
NK cell administration. Early data indicate that ex vivo expansion of NK cells
from healthy donors or from patients with cancer is robust, allowing multiple
infusions from a single apheresis. NK cells can transiently expand in vivo after
infusion. Allogeneic NK cells are not direct effectors of graft-versus-host
disease but this may occur if donor NK cells are infused after allogeneic
hematopoietic stem cell transplant, which may activate T cell alloreactivity. NK
cells can be directed with antibodies, or engineered using either transient
modification by electroporation of mRNA or prolonged gene expression by viral
transduction. Thus, expanded NK cells can be armed with activating receptors that
enhance their natural anti-tumor capacity or with chimeric antigen receptors that
can redirect them towards specific tumor targets. They can also be induced to
express cytokines that promote their autonomous growth, further supporting their
in vivo expansion. With the implementation of these approaches, expanded and
armed NK cells should ultimately become a powerful component of immunotherapy of
cancer.
PMID- 27497703
TI - Epilepsy comorbidities: Is clonazepam a friend or a foe?
PMID- 27497702
TI - Proposed caudal appendage classification system; spinal cord tethering associated
with sacrococcygeal eversion.
AB - INTRODUCTION: The most commonly used classification system for caudal appendages
(aka human tails) dates from the 1980s and classifies appendages (tails) as
either true tails or pseudotails. Advances in neuroimaging since the 1980s,
however, as well as an ever-increasing number of reported cases, have made this
system outdated. Sacrococcygeal eversion is a condition in which the distal
sacral and coccygeal vertebrae are curved in a retroverted rather than anteverted
direction. It can give rise to one type of caudal appendage. Sacrococcygeal
eversion has never been associated with spinal cord tethering in any previously
published reports. METHODS: We reviewed all cases of caudal appendage encountered
by pediatric neurosurgeons at Children's Hospital Colorado since 2000 in which
the appendage would be classified as a true tail by the most commonly used system
mentioned above. We also reviewed cases of sacrococcygeal eversion encountered
since 2000 by the same group of pediatric neurosurgeons. We searched the hospital
electronic medical record system for additional appendages using the terms
"caudal appendage" and "persistent human tail." RESULTS: We found 9 "true" tails
(as classified by the most commonly used system). All 9 were associated with
tethering or possible tethering of the spinal cord and 6 were associated with a
low-lying conus medullaris. There were 8 cases of sacrococcygeal eversion,
including 2 associated with Apert or Pfeiffer syndrome and fibroblast growth
factor receptor 2 (FGFR2) mutations; these have previously been reported. There
was a single case of sacrococcygeal eversion associated with Goldenhar or Turner
syndrome; the former was associated with a potentially tethering lesion. Four
cases of sacrococcygeal eversion not associated with any known syndrome were also
found; two of these were associated with tethering or potentially tethering
lesions. CONCLUSIONS: Most so-called true tails are likely cutaneous markers for
spinal dysraphism and spinal cord tethering and are not remnants of the embryonic
human tail. Sacrococcygeal eversion can be associated with spinal cord tethering.
Based on our cases, and on review of the literature, we devised a five-category
classification system for caudal appendages: (1) soft-tissue caudal appendages,
(2) bony caudal appendages, (3) bony caudal prominences, (4) true tails, and (5)
"other" caudal appendages.
PMID- 27497704
TI - Storage and transportation of Prochilodus lineatus (Characiformes) sperm prior to
cryopreservation.
AB - In this study we compared post-thaw quality of P. lineatus sperm frozen shortly
after collection, with sperm frozen after dilution and transportation, and up to
6h from collection. From each sperm sample (n=10 males) five aliquots were taken.
One aliquot was diluted in the freezing medium (1 sperm:8 glucose:1 methyl
glycol) and frozen ~20min after collection in the field (control), while the
other four aliquots were transported to the laboratory where freezing took place
3 or 6h after collection. From the transported aliquots, two were diluted 1:4 in
glucose solution before transportation (diluted samples), while the other two
were kept undiluted until freezing (undiluted samples). Thus the five treatments
were: control, undiluted-3h, diluted-3h, undiluted-6h and diluted-6h. Post-thaw
sperm was evaluated for membrane integrity, motility rate and velocities
(curvilinear=VCL; average path=VAP; straight line=VSL). Post-thaw membrane
integrity did not differ among the five treatments (48-60% intact sperm). Sperm
motility rate was similar (P>0.05) between control (64%) and undiluted samples
(60-62%) and higher (P<0.05) than that in diluted samples (35-45%), regardless
the time after collection when freezing took place. Velocities were higher in
control and in undiluted-3h samples (VCL of 254-265MUm/s, VAP of 219-244MUm/s and
VSL of 134-147MUm/s) than in diluted samples or samples frozen 6h after
collection. P. lineatus sperm can be transported/shipped to the laboratory
without decreasing its suitability for cryopreservation. Sperm should be kept
undiluted during storage and be frozen within 3h.
PMID- 27497705
TI - Peptidergic signaling in the crab Cancer borealis: Tapping the power of
transcriptomics for neuropeptidome expansion.
AB - The crab Cancer borealis has long been used as a model for understanding neural
control of rhythmic behavior. One significant discovery made through its use is
that even numerically simple neural circuits are capable of producing an
essentially infinite array of distinct motor outputs via the actions of locally
released and circulating neuromodulators, the largest class being peptides. While
much work has focused on elucidating the peptidome of C. borealis, no
investigation has used in silico transcriptome mining for peptide discovery in
this species, a strategy proven highly effective for identifying neuropeptides in
other crustaceans. Here, we mined a C. borealis neural transcriptome for putative
peptide-encoding transcripts, and predicted 200 distinct mature neuropeptides
from the proteins deduced from these sequences. The identified peptides include
isoforms of allatostatin A, allatostatin B, allatostatin C, CCHamide, crustacean
cardioactive peptide, crustacean hyperglycemic hormone, diuretic hormone 31
(DH31), diuretic hormone 44 (DH44), FMRFamide-like peptide, GSEFLamide,
HIGSLYRamide, insulin-like peptide (ILP), intocin, leucokinin, neuroparsin,
pigment dispersing hormone, pyrokinin, red pigment concentrating hormone, short
neuropeptide F and SIFamide. While some of the predicted peptides were known
previously from C. borealis, most (159) are new discoveries for the species,
e.g., the isoforms of CCHamide, DH31, DH44, GSEFLamide, ILP, intocin and
neuroparsin, which are the first members of these peptide families identified
from C. borealis. Collectively, the peptides predicted here approximately double
the peptidome known for C. borealis, and in so doing provide an expanded platform
from which to launch new investigations of peptidergic neuromodulation in this
species.
PMID- 27497706
TI - Mitochondria and the insect steroid hormone receptor (EcR): A complex
relationship.
AB - The actions of the insect steroid molting hormones, ecdysteroids, on the genome
of target cells has been well studied, but little is known of their extranuclear
actions. We previously showed in Rhodnius prolixus that much of the ecdysteroid
receptor (EcR) resides in the cytoplasm of various cell types and undergoes
shuttling between nucleus and cytoplasm with circadian periodicity, possibly
using microtubules as tracks for translocation to the nucleus. Here we report
that cytoplasmic EcR appears to be also involved in extranuclear actions of
ecdysteroids by association with the mitochondria. Western blots of subcellular
fractions of brain lysates revealed that EcR is localized in the mitochondrial
fraction, indicating an intimate association of EcR with mitochondria. Confocal
laser microscopy and immunohistochemistry using anti-EcR revealed abundant co
localization of EcR with mitochondria in brain neurons and their axons,
especially intense in the subplasmalemmal region, raising the possibility of EcR
involvement in mitochondrial functions in subplasmalemmal microdomains. When
mitochondria are dispersed by disruption of microtubules with colchicine, EcR
remains associated with mitochondria showing strong receptor association with
mitochondria. Treatment in vitro with ecdysteroids of brains of developmentally
arrested R. prolixus (containing neither ecdysteroids nor EcR) induces EcR and
abundant co-localization with mitochondria in neurons, concurrently with a sharp
increase of the mitochondrial protein COX 1, suggesting involvement of EcR in
mitochondrial function. These findings align EcR with various vertebrate steroid
receptors, where actions of steroid receptors on mitochondria are widely known
and suggest that steroid receptors across distant phyla share similar functional
attributes.
PMID- 27497707
TI - Gender and gonadal maturity stage identification of captive Chinese sturgeon,
Acipenser sinensis, using ultrasound imagery and sex steroids.
AB - Long lifespan and late maturation make it difficult to establish gamete maturity
and breeding age of captive endangered Chinese sturgeon, Acipenser sinensis. This
greatly handicaps timely breeding and future conservation stocking efforts. We
used ultrasound imagery and sex steroids to determine the gender and gonadal
maturity stage of captive Chinese sturgeon (age, 10-17years old). The
echogenicity of the reproductive organs and the respective morphology of the
gonads were described and two quantitative parameters po (proportion of the ovary
to the entire reproductive organs) and d (thickness of the reproductive organs)
were measured to characterize sex and maturity stage of Chinese sturgeon. Females
were accordingly placed fish into several categories: FII (FII-, FII, FII+), FIII
(FIII, FIII+) and FIV (FIV, FIV+) and FVI and males as MII, MIII, MIV, MV and
MVI. The accuracy of gender and maturity stage determination provided by
ultrasonographic methods was 72.7% for FII- ovary (n=11) and 76.2% for MII testis
(n=42). Accuracy of sex and maturity determination using only serum sex steroid
of testosterone (T) and estradiol-17beta (E2) was low (58-73%, depending on
maturity stage). However, when the two methods were used together, accuracy
increased sharply, especially for immature (II stage) females. In summary, of 151
Chinese sturgeon, whose sex and maturity stage were independently confirmed,
88.1% (n=133), 62.9% (n=95), and 96.7% (n=146) were successfully sexed and staged
using ultrasound, sex steroids, or both methods, respectively. The results
provide reliable non-invasive techniques for determining sex and gonadal
maturation of captive Chinese sturgeon. These methods can track individual gonad
characteristics over multi-year reproductive cycles, which will assist captive
broodstock management, artificial reproduction, and future conservation stocking.
PMID- 27497708
TI - G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve
transection, but does not improve nerve regeneration.
AB - Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug
candidate for improving the outcome after peripheral nerve injuries. We raised
the question if exogenous G-CSF can improve nerve regeneration following a
clinically relevant model - nerve transection and repair - in healthy and
diabetic rats. In short-term experiments, distance of axonal regeneration and
extent of injury-induced Schwann cell death was quantified by staining for
neurofilaments and cleaved caspase 3, respectively, seven days after repair.
There was no difference in axonal outgrowth between G-CSF-treated and non-treated
rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were
examined. However, G-CSF treatment caused a significant 13% decrease of cleaved
caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a
trend in diabetic rats. In the distal nerve segments of healthy rats a similar
trend was observed. In long-term experiments of healthy rats, regeneration
outcome was evaluated at 90days after repair by presence of neurofilaments, wet
weight of gastrocnemius muscle, and perception of touch (von Frey monofilament
testing weekly). The presence of neurofilaments distal to the suture line was
similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over
contralateral gastrocnemius muscles, and perception of touch at any time point,
were likewise not affected by G-CSF treatment. In addition, the inflammatory
response in short- and long-term experiments was studied by analyzing ED1
stainable macrophages in healthy rats, but in neither case was any attenuation
seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation
in Schwann cells in the short-term, but does not detectably affect the
inflammatory response, nor improve early or late axonal outgrowth or functional
recovery.
PMID- 27497709
TI - Group III mGluR8 negatively modulates TRPA1.
AB - Several lines of evidence indicate group III metabotropic glutamate receptors
(mGluRs) have systemic anti-hyperalgesic effects. We hypothesized this could
occur through modulation of TRP channels on nociceptors. This study used a
multifaceted approach to examine the interaction between group III mGluRs
(mGluR8) and transient receptor potential ankyrin 1 (TRPA1) on cutaneous
nociceptors in rats. Ca2+ imaging studies demonstrated co-localization and
functional coupling of TRPA1 and mGluR8, since 1MUM (S)-3,4
dicarboxyphenylglycine (DCPG) (mGluR8 agonist) significantly reduced Ca2+
mobilization produced by 30MUM mustard oil (MO), a TRPA1 agonist. Behavioral
studies demonstrated that 10mM MO produced mechanical hypersensitivity when
topically applied to the hind paw, significantly decreasing paw withdrawal
threshold (PWT) from 15g to 6g. However, administration of 30MUM DCPG prior to
10mM MO reversed this hypersensitivity such that PWT was not significantly
different from baseline. At the single-fiber level, compared to vehicle, 30MUM MO
significantly increased nociceptor activity and decreased mechanical threshold.
However, 30MUM DCPG reversed both of these MO-induced effects. Furthermore, DCPG
significantly reduced the number of MO-induced mechanically sensitive fibers.
Inhibition of protein kinase A (PKA) using Rp-cyclic 3',5'-hydrogen
phosphorothioate adenosine triethylammonium salt (RpCAMPS) (PKA inhibitor, 1 and
10MUM) significantly reduced MO-induced Ca2+ mobilization. Taken together, these
results show that group III mGluRs negatively modulate TRPA1 activity on
cutaneous nociceptors. Furthermore, it is likely that this modulation occurs
intracellularly at the level of the cAMP/PKA pathway. This study demonstrates
that group III agonists may be effective in the treatment of mechanical
hypersensitivity which can develop as a result of inflammation, nerve injury,
chemotherapy and other disease states.
PMID- 27497711
TI - Computational Cardiology - A New Discipline of Translational Research.
PMID- 27497710
TI - Successful lysis in massive pulmonary embolism with thrombus entrapped in PFO.
PMID- 27497712
TI - Post-marketing safety evaluation of the intravenous anti-influenza neuraminidase
inhibitor peramivir: A drug-use investigation in patients with high risk factors.
AB - Peramivir, the only injectable anti-influenza neuraminidase inhibitor medically
available in Japan at present, is considered first-line treatment in patients
with high risk factors for influenza exacerbation. We conducted a drug-use
investigation of peramivir in inpatients with high risk factors (old age,
pregnancy, and underlying disease such as chronic respiratory disease) from
January 2010 to March 2013. Data of 772 patients from 124 facilities across Japan
were collected; peramivir's safety in 770 patients and effectiveness in 688
patients were examined. In total, 412 adverse events were observed in 219
patients (28.4%). Of these, 155 events were adverse drug reactions (ADRs)
observed in 98 patients (12.7%). Major ADRs (>=2%) were increased aspartate
aminotransferase (5.1%), increased alanine aminotransferase (3.8%) and decreased
white blood cell count (2.5%). Fourteen serious ADRs were observed in 12 patients
(1.6%). All serious ADRs were resolved or improved except for two events for
which outcomes were unknown. Multivariate analyses revealed that ADR incidences
were significantly associated with these four backgrounds of patients: medical
history, no influenza vaccination, renal impairment and other infection(s). With
regard to its effectiveness, the median time to alleviation of both influenza
symptoms and fever was 3 days, including the first day of administration, which
was the same as in other previous surveillance studies. This surveillance study
indicated the safety of peramivir in the treatment of influenza inpatients with
high risk factors under routine clinical settings.
PMID- 27497713
TI - Development of a seminar on medical professionalism accompanying the dissection
course.
AB - INTRODUCTION: Medical professionalism is an increasingly important issue in
medical education. The dissection course represents a profound experience for
undergraduate medical students, which may be suitable to address competencies
such as self-reflection and professional behavior. MATERIAL AND METHODS: Based on
a needs assessment, a seminar on medical professionalism was developed to
parallel the dissection course. The conceptual framework for the teaching
intervention is experiential learning. Specific learning goals and an interview
guideline were formulated. After a pilot run, peer-teaching was introduced.
RESULTS: Over three terms (winter 2012/13, 2013/14, 2014/15), an average of 129
students voluntarily participated in the seminar, corresponding to 40% of the
student cohort. The evaluation (n=38) shows a majority of students agreeing that
the seminar offers support with this extraordinary situation in general and also
that the seminar helps them to become first impressions on how to cope with death
and dying in their later professional life as a doctor, and, that it also
provides them the means to reflect upon their own coping mechanisms. CONCLUSION:
Although not yet implemented as an obligatory course, the seminar is appreciated
and positively evaluated. Medical professionalism is an implicit aspect of the
dissection course. To emphasize its importance, a teaching intervention to
explicitly discuss this topic is advisable.
PMID- 27497714
TI - Chondral ossification centers next to dental primordia in the human mandible: A
study of the prenatal development ranging between 68 to 270mm CRL.
AB - The human mandible is said to arise from desmal ossification, which, however, is
not true for the entire body of the mandible: Meckel's cartilage itself is prone
to ossification, at least its anterior part in the canine and incisor region.
Also, within the coronoid and in the condylar processes there are cartilaginous
cores, which eventually undergo ossification. Furthermore, there are a number of
additional single cartilaginous islets arising in fetuses of 95mm CRL and more.
They are located predominantly within the bone at the buccal sides of the brims
of the dental compartments, mostly in the gussets between the dental primordia.
They become wedge-shaped or elongated with a diameter of around 150-500MUm and
were also found in older stages up to 225mm CRL, which was the oldest specimen
used in this study. This report is intended to visualize these single
cartilaginous islets histologically and in 3-D reconstructions in stereoscopic
images. Although some singular cartilaginous tissue within the mandible may be
remains of the decaying Meckel's cartilage, our 3-D reconstructions clearly show
that the aforementioned cartilaginous islets are independent thereof, as can be
derived from their separate locations within the mandibular bone. The reasons
that lead to these cartilaginous formations have remained unknown so far.
PMID- 27497715
TI - Newer Therapies for Amyloid Cardiomyopathy.
AB - The heart and the kidneys are the most commonly involved organs in systemic
amyloidosis. Cardiac involvement is associated with an increased morbidity,
treatment intolerance, and poorer overall survival. The most common types of
amyloidosis that are associated with cardiac involvement include light chain (AL)
amyloidosis and transthyretin (TTR) amyloidosis (both mutant and wild type). The
traditional first-line treatment for AL amyloidosis includes alkylator-based
chemotherapy or high-dose melphalan followed by autologous stem cell
transplantation (ASCT). Novel agents, including proteasome inhibitors,
immunomodulators, and monoclonal antibodies, have shown promising activity in
both frontline and relapsed settings. Orthotopic heart transplantation (OHT)
followed by ASCT has led to superior outcomes compared to OHT alone. Orthotopic
liver transplantation (OLT) is the first-line treatment for TTR amyloidosis.
However, progression of cardiac amyloidosis after OLT is often noted due to
deposition of wild TTR. Combined OLT and OHT also has a role in treatment and
leads to superior outcomes in carefully selected candidates. Pharmacologic
agents, including diflunisal, tafamidis, small interfering ribonucleic acid, and
doxycycline, have shown promising activity in stabilizing TTR from misfolding
into fibrils and are being actively investigated. Best supportive care and
management of heart failure symptoms with diuretics are a mainstay of treatment
in all cardiac amyloidosis subtypes. Robust data on the benefit of angiotensin
converting enzyme inhibitors, angiotensin receptor blockers, or beta blockers in
amyloid cardiomyopathy is lacking.
PMID- 27497716
TI - A randomized and blinded comparison of qPCR and NGS-based detection of aneuploidy
in a cell line mixture model of blastocyst biopsy mosaicism.
AB - PURPOSE: A subset of preimplantation stage embryos may possess mosaicism of
chromosomal constitution, representing a possible limitation to the clinical
predictive value of comprehensive chromosome screening (CCS) from a single
biopsy. However, contemporary methods of CCS may be capable of predicting
mosaicism in the blastocyst by detecting intermediate levels of aneuploidy within
a trophectoderm biopsy. This study evaluates the sensitivity and specificity of
aneuploidy detection by two CCS platforms using a cell line mixture model of a
mosaic trophectoderm biopsy. METHODS: Four cell lines with known karyotypes were
obtained and mixed together at specific ratios of six total cells (0:6, 1:5, 2:4,
3:3, 4:2, 5:1, and 6:0). A female euploid and a male trisomy 18 cell line were
used for one set, and a male trisomy 13 and a male trisomy 15 cell line were used
for another. Replicates of each mixture were prepared, randomized, and blinded
for analysis by one of two CCS platforms (quantitative polymerase chain reaction
(qPCR) or VeriSeq next-generation sequencing (NGS)). Sensitivity and specificity
of aneuploidy detection at each level of mosaicism was determined and compared
between platforms. RESULTS: With the default settings for each platform, the
sensitivity of qPCR and NGS were not statistically different, and 100 %
specificity was observed (no false positives) at all levels of mosaicism.
However, the use of previously published custom criteria for NGS increased
sensitivity but also significantly decreased specificity (33 % false-positive
prediction of aneuploidy). CONCLUSIONS: By demonstrating increased false-positive
diagnoses when reducing the stringency of predicting an abnormality, these data
illustrate the importance of preclinical evaluation of new testing paradigms
before clinical implementation.
PMID- 27497717
TI - Towards physics of neural processes and behavior.
AB - Behavior of biological systems is based on basic physical laws, common across
inanimate and living systems, and currently unknown physical laws that are
specific for living systems. Living systems are able to unite basic laws of
physics into chains and clusters leading to new stable and pervasive relations
among variables (new physical laws) involving new parameters and to modify these
parameters in a purposeful way. Examples of such laws are presented starting from
the tonic stretch reflex. Further, the idea of control with referent coordinates
is formulated and merged with the idea of hierarchical control and the principle
of abundance. The notion of controlled stability of behaviors is linked to the
idea of structured variability, which is a common feature across living systems
and actions. The explanatory and predictive power of this approach is illustrated
with respect to the control of both intentional and unintentional movements, the
phenomena of equifinality and its violations, preparation to quick actions,
development of motor skills, changes with aging and neurological disorders, and
perception.
PMID- 27497719
TI - Special Issue on the Adolescent Brain.
PMID- 27497718
TI - The organizing actions of adolescent gonadal steroid hormones on brain and
behavioral development.
AB - Adolescence is a developmental period characterized by dramatic changes in
cognition, risk-taking and social behavior. Although gonadal steroid hormones are
well-known mediators of these behaviors in adulthood, the role gonadal steroid
hormones play in shaping the adolescent brain and behavioral development has only
come to light in recent years. Here we discuss the sex-specific impact of gonadal
steroid hormones on the developing adolescent brain. Indeed, the effects of
gonadal steroid hormones during adolescence on brain structure and behavioral
outcomes differs markedly between the sexes. Research findings suggest that
adolescence, like the perinatal period, is a sensitive period for the sex
specific effects of gonadal steroid hormones on brain and behavioral development.
Furthermore, evidence from studies on male sexual behavior suggests that
adolescence is part of a protracted postnatal sensitive period that begins
perinatally and ends following adolescence. As such, the perinatal and
peripubertal periods of brain and behavioral organization likely do not represent
two discrete sensitive periods, but instead are the consequence of normative
developmental timing of gonadal hormone secretions in males and females.
PMID- 27497720
TI - Influence of chronic endurance exercise training on conduit artery retrograde and
oscillatory shear in older adults.
AB - PURPOSE: With aging, there tends to be an increase in retrograde and oscillatory
shear in peripheral conduit arteries of humans. Whether the increase in shear
rate is due to the aging process or an effect of a less active lifestyle that
often accompanies aging is unknown. Therefore, we examined whether chronic
endurance exercise training attenuates conduit artery retrograde and oscillatory
shear in older adults. METHODS: Brachial and common femoral artery mean blood
velocities and diameter were determined via Doppler ultrasound under resting
conditions, and shear rate was calculated in 13 young (24 +/- 2 years), 17 older
untrained (66 +/- 3 years), and 16 older endurance exercise-trained adults (66 +/
7 years). RESULTS: Brachial artery retrograde (-9.1 +/- 6.4 vs. -12.6 +/- 9.4 s(
1); P = 0.35) and oscillatory (0.14 +/- 0.08 vs. 0.14 +/- 0.08 arbitrary units; P
= 0.99) shear were similar between the older trained and untrained groups,
whereas brachial artery retrograde and oscillatory shear were greater in older
untrained compared to young adults (-5.0 +/- 3.4, 0.08 +/- 0.05 s(-1) arbitrary
units, P = 0.017 and 0.048, respectively). There was no difference between the
young and older trained brachial retrograde (P = 0.29) and oscillatory (P = 0.07)
shear. Common femoral artery retrograde (-6.3 +/- 2.9 s(-1)) and oscillatory
(0.21 +/- 0.08 arbitrary units) shear were reduced in older trained compared to
the older untrained group (-10.4 +/- 4.1 and 0.30 +/- 0.09 s(-1) arbitrary units,
both P = 0.005 and 0.006, respectively), yet similar to young adults (-7.1 +/-
3.5 and 0.19 +/- 0.06 s(-1) arbitrary units, P = 0.81 and 0.87, respectively).
CONCLUSION: Our results suggest that chronic endurance exercise training in older
adults ameliorates retrograde and oscillatory shear rate patterns, particularly
in the common femoral artery.
PMID- 27497721
TI - Preparation of core-shell magnetic molecular imprinted polymer with binary
monomer for the fast and selective extraction of bisphenol A from milk.
AB - In the current study, a new strategy for the extraction of bisphenol A (BPA) from
milk has been employed by using surface-imprinted core-shell magnetic beads,
prepared by the reversible addition-fragmentation chain transfer (RAFT)
polymerization. In order to obtain highly selective recognition cavities, an
enhanced imprinting method based on binary functional monomers, e.g. 4
vinylpyridine (4-VP) and beta-cyclodextrin (beta-CD), was chosen for BPA
imprinting. The morphological and magnetic properties of the Fe3O4-MIP beads were
characterized by Transmission Electron Microscopy (TEM), Fourier Transform
Infrared (FT-IR) Spectroscopy, Thermogravimetric Analysis (TGA), and Vibrating
Sample Magnetometer (VSM). The characterization results suggested that MIP was
synthesized evenly on Fe3O4-SiO2 surface. The adsorption experiments revealed
that Fe3O4-MIPs showed better extraction capacity and selectivity toward BPA and
its analogues than the non-imprinted polymers (NIPs). The saturation capacity of
Fe3O4-MIP was 17.98mg/g. In milk samples, the present method displayed a lower
the detection thresholds, down to 3.7MUg/L. The recoveries of BPA in milk samples
for three concentrations were found to be within 99.21%, 98.07% and 97.23%,
respectively to three concentrations: 1.0MUmol/L, 10.0mol/L, 100.0MUmol/L. Thus,
the MIPs can be used for remove BPA in milk samples.
PMID- 27497722
TI - Enantioselective determination of citrulline and ornithine in the urine of d
amino acid oxidase deficient mice using a two-dimensional high-performance liquid
chromatographic system.
AB - Two-dimensional high-performance liquid chromatographic (2D-HPLC) and 2D-HPLC
mass spectrometric (2D-HPLC-MS) systems have been designed and developed for the
determination of the citrulline (Cit) and ornithine (Orn) enantiomers. Several d
amino acids have already been identified as novel physiologically active
molecules and biomarkers, and the enantioselective evaluation of the amounts,
distributions and metabolisms of non-proteinogenic amino acids gain as well
increasing interest. In the present study, highly selective analytical methods
were developed using a capillary monolithic ODS column (0.53mm i.d. x 1000mm) for
the reversed-phase separation of the target analytes from the matrix compounds in
the first dimension, and a narrowbore-Pirkle type enantioselective column,
KSAACSP-105S (1.5mm i.d. x 250mm), was used for the enantiomer separation in the
second dimension. The amino acids were analyzed after pre-column derivatization
with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) and detected by the
fluorescence detector and MS. The systems were applied to the urine of d-amino
acid oxidase (DAO) deficient B6DAO- mice and control C57BL mice to evaluate the
presence and metabolism of the Cit and Orn enantiomers in mammals. As a result,
all of the 4 target enantiomers (d-Cit, l-Cit, d-Orn, l-Orn) were found in the
urine of both strains. The %D value of Cit (d-Cit/Cit*100) increased about 3-fold
in the urine of the DAO deficient mice and that of Orn also tended to increase
with the DAO deficiency. These results were definitely confirmed by a 2D-HPLC-MS
detection system. Further investigations about the biological significance of
these d-isomers are currently ongoing.
PMID- 27497723
TI - Comparison of the homogeneity of mRNAs encoding SFRP5, FZD4, and Fosl1 in post
injury intervals: Subcellular localization of markers may influence wound age
estimation.
AB - The inter-group heterogeneity and intra-group homogeneity of relative expression
are very necessary when the mRNA were used to determine wound age accurately in
forensic medicine. The aim of this study was to assess the intra-group
homogeneity of SFRP5, FZD4 and Fosl1 mRNAs in post-injury intervals. The
corresponding proteins show different subcellular locations. A total of 78
Sprague-Dawley rats were divided into control and contusion groups. At 4, 8, 12,
16, 20, 24, 28, 32, 36, 40, 44, or 48 h (n = 6 per group) after contusion (under
anesthesia by chloral hydrate intraperitoneally), the rats were sacrificed using
a lethal dose of pentobarbital, and samples of the injured muscles were
collected. The raw Ct values of SFRP5, FZD4, and Fosl1 mRNAs were obtained using
real-time PCR. After normalized to RPL13 mRNA levels, the coefficient of
variation (CV) and the relative average deviation (d%) of each normalized Ct, and
their relative expression levels, were calculated in each post-injury interval.
Two methods were applied to compare the homogeneity of the three genes. First,
each gene was given a score based on its CV value in each post-injury interval.
Then, the sum of the 13 scores was calculated; a low sum indicated high
homogeneity. Second, the 13 calculated CVs or d%s were used as raw data, which
was described as the mean +/- SD. Based on this mean +/- SD, a CV of the CVs and
a d% of the d%s were calculated to represent the variation; a low value indicated
high homogeneity. The sum of the variability of FZD4 mRNA was lower than those of
the SFRP5 and Fosl1 mRNAs, consistent with the results that the FZD4 mRNA had the
lowest mean, the smallest CV of all CVs, and the smallest d% of all d%s, among
the three genes. In conclusion, these data indicated that mRNA encoding
membranous FZD4 was likely to be more homogeneous than those encoding SFRP5 and
Fosl1 within post-injury intervals.
PMID- 27497724
TI - The Care Programme Approach, sexual violence and clinical practice in mental
health.
AB - INTRODUCTION: Research in Sexual Assault Referral Centres has shown that 40% of
those attending are known to mental health services. The question we posed in
this study was to what extent do mental health services know about this group?
This was a pertinent question to ask as in 2008 the Department of Health (DH)
amended the Care Programme Approach (CPA) to include a question on sexual
abuse/violence as part of the overall assessment. AIMS: To assess the extent to
which Mental health Trusts were implementing DH guidance on the CPA in relation
to assessment of sexual violence and abuse. METHOD: 1. Freedom of Information
(FOI) requests were sent to all Mental Health Trusts. 2. The Information base at
the Health and Social Care Information Centre (HSCIC) was interrogated as Trusts
can make returns on this CPA question, however it is not mandatory. RESULTS: 1.
The FOI requests revealed that: only 66% of staff were trained to 'ask the
question' (range 35-100%) and only five out of 53 Trusts audited whether the
question was asked. 2. The HSCIC data revealed that in 2014/15 there were 335,727
people in the CPA in England and there was a record in only 17% of cases of the
question being asked. Over half (57%) of the 69 providers who did not submit any
information on the indicator in 2014/15 as well as, for those 30 providers who
did submit information, the data field was only 41% complete. CONCLUSIONS: The
impetus for 'asking the question' first established in 2008 with the
establishment of eight pilot training programmes, has been lost. It is clear that
Trusts are not training adequate number of staff nor are they returning useable
data to HSCIC. If 40% of people attending SARCs are known to mental health
services we suspect that few staff in mental health trusts known much about such
a referral. Research shows convincingly that sexual violence and abuse plays a
clear role in the aetiology of mental health disorders. A history of such
violence/abuse should be always established (or otherwise).
PMID- 27497725
TI - The accuracy of body mass prediction for elderly specimens: Implications for
paleoanthropology and legal medicine.
AB - Different practices in paleoanthropology and legal medicine raise questions
concerning the robustness of body mass (BM) prediction. Integrating personal
identification from body mass estimation with skeleton is not a classic approach
in legal medicine. The originality of our study is the use of an elderly sample
in order to push prediction methods to their limits and to discuss about
implications in paleoanthropology and legal medicine. The aim is to observe the
accuracy of BM prediction in relation to the body mass index (BMI, index of
classification) using five femoral head (FH) methods and one shaft (FSH) method.
The sample is composed of 41 dry femurs obtained from dissection where age (c. 82
years) and gender are known, and weight (c. 59.5 kg) and height are measured upon
admission to the body leg service. We show that the estimation of the mean BM of
the elderly sample is not significantly different to the real mean BM when the
appropriate formula is used for the femoral head diameter. In fact, the best
prediction is obtained with the McHenry formula (1992), which was based on a
sample with an equivalent average mass to that of our sample. In comparison,
external shaft diameters, which are known to be more influenced by mechanical
stimuli than femoral head diameters, yield less satisfactory results with the
McHenry formula (1992) for shaft diameters. Based on all the methods used and the
distinctive selected sample, overestimation (always observed with the different
femoral head methods) can be restricted to 1.1%. The observed overestimation with
the shaft method can be restricted to 7%. However, the estimation of individual
BM is much less reliable. The BMI has a strong impact on the accuracy of
individual BM prediction, and is unquestionably more reliable for individuals
with normal BMI (9.6% vs 16.7% for the best prediction error). In this case, the
FH method is also the better predictive method but not if we integrate the total
sample (i.e., the FSH method is better with more varied BMI). Finally, the
estimation of the mean BM of a sample can be used with more confidence compared
to the estimation of individual BM. The former is very useful in an evolutionary
perspective whereas the latter should be used in keeping with the information
gathered on the studied specimen in order to reduce prediction errors. Finally,
the BM estimation can be a parameter to consider for personal identification.
PMID- 27497726
TI - Consideration of interaction between nanoparticles and food components for the
safety assessment of nanoparticles following oral exposure: A review.
AB - Nanoparticles (NPs) are increasingly used in food, and the toxicity of NPs
following oral exposure should be carefully assessed to ensure the safety.
Indeed, a number of studies have shown that oral exposure to NPs, especially
solid NPs, may induce toxicological responses both in vivo and in vitro. However,
most of the toxicological studies only used NPs for oral exposure, and the
potential interaction between NPs and food components in real life was ignored.
In this review, we summarized the relevant studies and suggested that the
interaction between NPs and food components may exist by that 1) NPs directly
affect nutrients absorption through disruption of microvilli or alteration in
expression of nutrient transporter genes; 2) food components directly affect NP
absorption through physico-chemical modification; 3) the presence of food
components affect oxidative stress induced by NPs. All of these interactions may
eventually enhance or reduce the toxicological responses induced by NPs following
oral exposure. Studies only using NPs for oral exposure may therefore lead to
misinterpretation and underestimation/overestimation of toxicity of NPs, and it
is necessary to assess the synergistic effects of NPs in a complex system when
considering the safety of NPs used in food.
PMID- 27497727
TI - The immune responses in juvenile rockfish, Sebastes schlegelii for the stress by
the exposure to the dietary lead (II).
AB - The aim of this study was to evaluate the lead toxic effects on the stress
parameters and immune responses of Sebastes schlegelii. Juvenile rockfish, S.
schlegelii (mean length 14.2+/-1.9cm, and mean weight 57.3+/-5.2g) were exposed
for 4 weeks with the different levels of dietary lead (Pb(2+)) at 0, 30, 60, 120
and 240mg/L. The plasma cortisol and heat shock protein 70 was evaluated as
stress indicators. The plasma cortisol of S. schlegelii was significantly
increased in response to the dietary lead exposure over 60mg/kg at 2 weeks. After
4 weeks, the significant increase in the plasma cortisol was observed at 30 and
60mg/kg, but the level was decreased over 120mg/kg. The heat shock protein 70 of
S. schlegelii was also notably elevated over 60mg/kg for 4 weeks. In the immune
response, the immunoglobulin M of S. schlegelii was considerably increased over
120mg/kg for 4 weeks. A significant increase was observed in lysozyme activity.
The plasma lysozyme activity of S. schlegelii was elevated over 120mg/kg after 2
weeks and 60mg/kg after 4 weeks, and kidney lysozyme activity was also increased
at 240mg/kg after 2 weeks and over 120mg/kg after 4 weeks. The results indicate
that dietary Pb exposure can cause a significant stress and immune stimulation of
S. schlegelii.
PMID- 27497728
TI - Zidovudine and isoniazid induced liver toxicity and oxidative stress: Evaluation
of mitigating properties of silibinin.
AB - HIV/AIDS patients are more prone for opportunistic TB infections and they are
administered the combined regimen of anti-retroviral drug zidovudine (AZT) and
isoniazid (INH) for therapy. However, AZT+INH treatment has been documented to
induce injury and remedial measures to prevent this adversity are not clearly
defined. Silibinin (SBN) is a natural hepatoprotective principle isolated from
medicinal plant Silybum marianum and is currently used for therapy of various
liver diseases. This study investigate the hepatotoxic potentials of AZT alone,
INH alone and AZT+INH treatments and the mitigating potentials of SBN against
these drugs induced toxic insults of liver in rats. Separate groups of rats (n=6
in each group) were administered AZT alone (50mg/kg b.w.), INH alone (25mg/kg,
b.w.), AZT+INH (50mg/kg, b.w. and 25mg/kg, b.w.), SBN alone (100mg/kg, b.w.) and
SBN+AZT+INH daily for sub-chronic period of 45days orally. The control rats
received saline/propylene glycol. INH alone and AZT+INH-induced parenchymal cell
injury and cholestasis of liver was evidenced by highly significant increase in
the activities of marker enzymes (aspartate and alanine transaminase, alkaline
phosphatase, argino succinic acid lyase), bilirubin, protein, oxidative stress
parameters (lipid peroxidation, superoxide dismutase, catalase, reduced
glutathione, vitamins C and E) and membrane bound ATPases were evaluated in
serum/liver tissue homogenates. Histopathological studies show ballooning
degradation, inflammatory lesions, lipid deposition and hydropic changes in the
liver tissue. All the above biochemical and pathological changes induced by
AZT+INH treatments were mitigated in rats receiving SBN simultaneously with these
hepatotoxins, indicating its hepatoprotective and antioxidant potentials against
AZT+INH-induced hepatotoxicity. The moderate hepatoprotective and oxidant
potentials of SBN could be due to its low bioavailability and this deficiency
could be prevented by supplementation of phosphatidylcholines and studies are
warranted on these lines to improve the therapeutic efficiency of SBN.
PMID- 27497729
TI - beta-eudesmol, a sesquiterpene from Teucrium ramosissimum, inhibits superoxide
production, proliferation, adhesion and migration of human tumor cell.
AB - Reactive oxygen species are well-known mediators of various biological responses.
Recently, new homologues of the catalytic subunit of NADPH oxidase have been
discovered in non phagocytic cells. These new homologues (Nox1-Nox5) produce low
levels of superoxides compared to the phagocytic homologue Nox2/gp91phox. In this
study we examined the effect of beta-eudesmol, a sesquiterpenoid alcohol isolated
from Teucrium ramosissimum leaves, on proliferation, superoxide anion production,
adhesion and migration of human lung (A549) and colon (HT29 and Caco-2) cancer
cell lines. Proliferation of tumor cells was inhibited by beta-eudesmol. It also
significantly inhibited superoxide production in A549 cells. Furthermore, beta
eudesmol inhibited adhesion and migration of A549 and HT29 cell. These results
demonstrate that beta-eudesmol may be a novel anticancer agent for the treatment
of lung and colon cancer by different ways: by inhibition of superoxide
production or by blocking proliferation, adhesion and migration.
PMID- 27497730
TI - A metabolic profiling analysis of the nephrotoxicity of acyclovir in rats using
ultra performance liquid chromatography/mass spectrometry.
AB - Acyclovir (ACV) exposure is a common cause of acute kidney injury (AKI). The
toxicity mechanism of ACV has always been a matter of debate. The present study
investigated into the time-effect relationship and dose-effect relationship of
ACV-induced nephrotoxicity in rats using metabonomics. Twenty-four rats were
randomly divided into four groups: a 0.9% NaCl solution group, and 100, 300, and
600mg/kg ACV-treated groups; the ACV or vehicle solution was administered with a
single intravenous injection. Urine was collected at different time periods (12h
before administration, and 0-6h, 7-12h, and 13-24h after administration). Routine
urinalysis was conducted by a urine automatic analyzer. Renal markers, including
urine urea nitrogen, urine creatinine, and urinary N-acetyl-beta-d
glucosaminidase (NAG) activity, were determined using established protocols.
Urinary metabolites were evaluated using ultra performance liquid
chromatography/mass spectrometry (UPLC/MS). In the ACV-treated rats, increased
levels of protein (PRO), occult blood (BLD), white blood cell (WBC), and NAG
activity in urine were observed, while the urine creatinine and urea nitrogen
levels showed a decrease compared with the control. Moreover, urine metabolites
significantly changed after the treatment with ACV, and all the effects induced
by ACV were dose-time dependent. Finally, 4 metabolites (guanine, 4
guanidinobutyric acid, creatinine, and urea) were identified, which can be used
for further research on the mechanism of ACV-induced nephrotoxicity.
PMID- 27497732
TI - Composite graft aortic root reconstruction: Reproducible, durable, and
uncomplicated.
PMID- 27497731
TI - Historical perspectives of The American Association for Thoracic Surgery: Richard
A. Jonas.
PMID- 27497733
TI - Functional induction of P-glycoprotein efflux pump by phenyl benzenesulfonamides:
Synthesis and biological evaluation of T0901317 analogs.
AB - N-(2,2,2-Trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1
(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317, 6) is a potent
activator of pregnane-X-receptor (PXR), which is a nuclear receptor controlling P
gp expression. Herein, we aimed to investigate P-gp induction activity of
T0901317 and establish its structure-activity relationship. T0901317 along with a
series of N-triazolyl-methylene-linked benzenesulfonamides were synthesized and
screened for P-gp induction activity using a rhodamine-123 based efflux assay in
the P-gp overexpressing human adenocarcinoma LS-180 cells, wherein several
compounds showed potent P-gp induction activity at 5 MUM. Treatment with benzene
sulphonamides led to the decrease in intracellular accumulation of a fluorescent
P-gp substrate rhodamine-123 up to 48% (control 100%). In the western-blot
studies, T0901317 (6) and its triazole linked analog 26e at 5 MUM displayed
induction of P-gp expression in LS180 cells. These compounds were non-toxic in LS
180 and human neuroblastoma SH-SY5Y cells (IC50 > 50 MUM). The compound 26e
showed significant P-gp induction even at 0.3 MUM, indicating an excellent
therapeutic window. These results clearly indicate promise of this class of
compounds as potential agents to enhance amyloid-beta clearance in Alzheimers
patients.
PMID- 27497734
TI - Attention, reward, and inhibition: symptomatic features of ADHD and issues for
offenders in the criminal justice system.
AB - Although the relationship between criminal activity and ADHD has been heavily
studied, this paper reviews a largely neglected area of academic discourse: how
symptoms of ADHD that often contribute to offending behavior may also potentially
create further problems for offenders with ADHD after they come into contact with
the criminal justice system and pilot their way through the legal process. The
main symptoms of ADHD that are primarily connected to criminal offending are
examined and contextualized with respect to diagnosed offenders' experiences with
the justice system. Symptoms of ADHD, specifically reward deficiency, behavioral
inhibition, and attention deficits, may affect whether individuals will be
successful in their experiences in court, with probation, and during
incarceration. This is especially true for individuals whose ADHD diagnoses are
unknown to the criminal justice system or have never been formally diagnosed.
Actors in the criminal justice need to be aware of the symptomatic features and
behavioral patterns of offenders with ADHD in order to recognize and identify
these offenders, and correspondingly, to refer them to mental health services.
Recognizing that at least some of an offender's behavior may be related to
symptoms of ADHD will help the criminal justice system better provide
recommendations regarding sentencing, probation, and treatment provisions, as
well as better ensure that offenders with ADHD have a more successful and just
experience in their interactions with the criminal justice system.
PMID- 27497735
TI - Effects of insulin therapy on porosity, non-enzymatic glycation and mechanical
competence in the bone of rats with type 2 diabetes mellitus.
AB - Type 2 diabetes mellitus increases skeletal fragility; however, the contributing
mechanisms and optimal treatment strategies remain unclear. We studied the
effects of diabetes and insulin therapy on non-enzymatic glycation (NEG),
cortical porosity (Ct.Po) and biomechanics of the bone tissue in Zucker Diabetic
Fatty (ZDF) rats. Eleven-week old ZDF diabetic and non-diabetic rats were given
insulin to achieve glycaemic control or vehicle seven days per week over twelve
weeks (insulin dose adapted individually 0.5 international units (IU) at week 1
to 13.0IU at week 12). The right femora were excised, micro-CT scanned, and
tested in 3-point bending to measure biomechanics. NEG of the midshaft was
determined from bulk fluorescence. Diabetes led to increased NEG (+50.1%,
p=0.001) and Ct.Po (+22.9%, p=0.004), as well as to reduced mechanical competence
(max. stress: -14.2%, p=0.041, toughness: -29.7%, p=0.016) in the bone tissue.
NEG and Ct.Po both correlated positively to serum glucose (NEG: R(2)=0.41,
p<0.001, Ct.Po: R(2)=0.34, p=0.003) and HbA1c (NEG: R(2)=0.42, p<0.001, Ct.Po:
R(2)=0.28, p=0.008) levels, while NEG correlated negatively with bone
biomechanics (elastic modulus: R(2)=0.21, p=0.023, yield stress: R(2)=0.17,
p=0.047). Twelve weeks of insulin therapy had no significant effect on NEG or
Ct.Po, and was unable to improve the mechanical competence of the bone tissue. A
reduction of mechanical competence was observed in the bone tissue of the
diabetic rats, which was explained in part by increased collagen NEG. Twelve
weeks of insulin therapy did not alter NEG, Ct.Po or bone biomechanics. However,
significant correlations between NEG and serum glucose and HbA1c were observed,
both of which were reduced with insulin therapy. This suggests that a longer
duration of insulin therapy may be required to reduce the NEG of the bone
collagen and restore the mechanical competence of diabetic bone.
PMID- 27497736
TI - Sclerostin, cardiovascular disease and mortality: a systematic review and meta
analysis.
AB - BACKGROUND AND AIM: Chronic kidney disease mineral and bone disorder (CKD-MBD) is
associated with increased morbidity and mortality. Several cross-sectional
studies investigated the association of serum sclerostin levels with mortality
and vascular calcification. We aimed to investigate the effect of sclerostin on
cardiovascular events (CVE), all-cause/cardiovascular mortality and vascular
calcification in patients with CKD through systematic review and meta-analysis.
The primary outcome was the association between sclerostin level and development
of fatal and nonfatal CVE and all-cause mortality. MATERIALS AND METHODS: A
literature search was performed using electronic databases Medline Ovid/Medline,
PubMed/Medline, EMBASE and ISI Web of Science. Extracted hazard ratios from the
included study protocols were pooled separately using the random-effects model
(DerSimonian Laird). The equivalent z test was performed for each pooled HR, and
if p < 0.05 it was considered statistically significant. RESULTS: In our final
analysis, we included nine observational prospective studies involving 1788
patients (minimum 91 and maximum 673 patients). For the all-cause mortality,
three studies with 503 patients showed that sclerostin levels were not
significantly associated with all-cause mortality risk (HR = 1.01, 95 % CI 0.99
1.03, p = 0.16; heterogeneity chi 2 = 12.24, I 2 = 84 %, p = 0.002). For
cardiovascular mortality, two studies with 412 patients showed that sclerostin
levels were not significantly associated with cardiovascular mortality risk (HR =
1.03, 95 % CI 0.99-1.07, p = 0.17; heterogeneity chi 2 = 10.74, I 2 = 91 %, p =
0.001). CONCLUSION: Although the studies are mostly small in size, heterogeneous
and have conflicting results, we have demonstrated that serum sclerostin levels
were not associated with all-cause and cardiovascular mortality.
PMID- 27497737
TI - The effect of hemodialysis on balance measurements and risk of fall.
AB - BACKGROUND: Patients with end-stage renal disease (ESRD) have increased risk of
falls and fall-related complications. Other than aging and factors related to
chronic kidney disease, treatment of hemodialysis may also contribute to this
increased risk. The aim of this study was to demonstrate the impairment of
balance after a session of hemodialysis with a quantitative assessment and reveal
an increased fall risk that would possibly be related to treatment of
hemodialysis for patients on maintenance hemodialysis. METHODS: Fifty-six
patients with ESRD on chronic hemodialysis program and 53 healthy individuals
were involved in this study. Fall Index percentages were calculated, and fall
risk categories were determined for all patients and healthy controls using
Tetrax posturography device (Sunlight Medical Ltd Israel). The patient group was
evaluated twice for balance, before and after a routine session of hemodialysis.
RESULTS: Fall Index scores of healthy controls were lower than that of ESRD
patients (p = 0.001). In the patient group, we found the mean Fall Index to be
significantly higher at the post-dialysis assessment compared to the pre-dialysis
assessment (p = 0.003). The number of patients with high risk of falling also
increased at the post-dialysis assessment yet the difference did not reach
significance. Fall Index was correlated with the increase in age only at the pre
dialysis balance measurement (p = 0.038). Patients with better dialysis adequacy
had significantly lower Fall Index scores than the others at the pre-dialysis
balance measurement (p = 0.004). The difference was not significant at the post
dialysis measurement. CONCLUSIONS: In the current study, we evaluated the balance
of ESRD patients before and after a routine session of hemodialysis treatment.
This is the first study to investigate the effect of hemodialysis on balance,
using an electronic posturographic balance system. We found the Fall Index score
to be significantly higher after hemodialysis, indicating a negative effect of
hemodialysis on postural stability. As expected, our data showed an increased
Fall Index score correlated with the increase in age both in ESRD patients and in
healthy controls. However, the correlation with age was not observed for the
patient group at the post-dialysis balance measurement. We might conceive that
young patients with ESRD are also prone to fall risk after a session of
hemodialysis. Methods that provide quantitative assessment for fall risk could be
rather beneficial for high-risk populations such as patients on maintenance
hemodialysis.
PMID- 27497739
TI - Short-day signals are crucial for the induction of anthocyanin biosynthesis in
Begonia semperflorens under low temperature condition.
AB - The leaves of Begonia semperflorens accumulate anthocyanins and turn red in
autumn in sub-temperate areas. This induction of anthocyanin biosynthesis in
autumn has been attributed to the effects of low temperature, but the effects of
different light regimes on this process are still being debated. In the present
work, short days were found to be necessary for anthocyanin biosynthesis at low
temperature. Under the same low-temperature conditions, Begonia seedlings grown
under the short-day condition accumulated more carbohydrates and abscisic acid
(ABA), which both induce anthocyanin biosynthesis. However, fewer carbohydrates
and more gibberellin (GA) accumulated under the long-day conditions to maintain
growth, which blocked anthocyanin biosynthesis and resulted in a lack of
increases in the activities of dihydroflavonol 4-reductase (DFR) and flavonoid-3
O-glucosyl transferase (UFGT). Consequently, carbon flux, which was altered due
to the blockade of anthocyanin synthesis, was channelled into the production of
quercetin and phenolic acids but not lignin.
PMID- 27497738
TI - Assortative mating can impede or facilitate fixation of underdominant alleles.
AB - Underdominant mutations have fixed between divergent species, yet classical
models suggest that rare underdominant alleles are purged quickly except in small
or subdivided populations. We predict that underdominant alleles that also
influence mate choice, such as those affecting coloration patterns visible to
mates and predators alike, can fix more readily. We analyze a mechanistic model
of positive assortative mating in which individuals have n chances to sample
compatible mates. This one-parameter model naturally spans random mating (n=1)
and complete assortment (n->infinity), yet it produces sexual selection whose
strength depends non-monotonically on n. This sexual selection interacts with
viability selection to either inhibit or facilitate fixation. As mating
opportunities increase, underdominant alleles fix as frequently as neutral
mutations, even though sexual selection and underdominance independently each
suppress rare alleles. This mechanism allows underdominant alleles to fix in
large populations and illustrates how life history can affect evolutionary
change.
PMID- 27497740
TI - Salt stress induces differential regulation of the phenylpropanoid pathway in
Olea europaea cultivars Frantoio (salt-tolerant) and Leccino (salt-sensitive).
AB - Olive tree (Olea europaea L.) is an important crop in the Mediterranean Basin
where drought and salinity are two of the main factors affecting plant
productivity. Despite several studies have reported different responses of
various olive tree cultivars to salt stress, the mechanisms that convey tolerance
and sensitivity remain largely unknown. To investigate this issue, potted olive
plants of Leccino (salt-sensitive) and Frantoio (salt-tolerant) cultivars were
grown in a phytotron chamber and treated with 0, 60 and 120mM NaCl. After forty
days of treatment, growth analysis was performed and the concentration of sodium
in root, stem and leaves was measured by atomic absorption spectroscopy. Phenolic
compounds were extracted using methanol, hydrolyzed with butanol-HCl, and
quercetin and kaempferol quantified via high performance liquid-chromatography
electrospray-mass spectrometry (HPLC-ESI-MS) and HPLC-q-Time of Flight-MS
analyses. In addition, the transcripts levels of five key genes of the
phenylpropanoid pathway were measured by quantitative Real-Time PCR. The results
of this study corroborate the previous observations, which showed that Frantoio
and Leccino differ in allocating sodium in root and leaves. This study also
revealed that phenolic compounds remain stable or are strongly depleted under
long-time treatment with sodium in Leccino, despite a strong up-regulation of key
genes of the phenylpropanoid pathway was observed. Frantoio instead, showed a
less intense up-regulation of the phenylpropanoid genes but overall higher
content of phenolic compounds. These data suggest that Frantoio copes with the
toxicity imposed by elevated sodium not only with mechanisms of Na+ exclusion,
but also promptly allocating effective and adequate antioxidant compounds to more
sensitive organs.
PMID- 27497741
TI - Overexpression of CHMP7 from rapeseed and Arabidopsis causes dwarfism and
premature senescence in Arabidopsis.
AB - Endosomal sorting complexes required for transport (ESCRT) are well known in
mammalians and yeast and plays an essential role in the formation of multi
vesicular bodies. Accumulating evidence has shown that ESCRT proteins contribute
to proper plant development. CHMP7 (charged multi-vesicular body protein 7) is an
ESCRT-III-related protein and functions in the endosomal sorting pathway in
humans. However, its function in plants has not been explored in detail. In this
study, we isolate the putative homolog of CHMP7 from rapeseed, BnCHMP7, which
contains eight exons and encodes a protein consisting of 423 amino acid residues.
Compared with the wild-type, overexpression of BnCHMP7 in Arabidopsis disturbs
plant growth and decreases seed yield. Moreover, the transgenic plants also
display early leaf senescence and hypersensitivity to dark treatment due to
defects in autophagic degradation. Further study showed that BnCHMP7 is highly
expressed in leaves and that YFP-BnCHMP7 is predominantly localized in endosome.
Compared with human CHMP7, we found that BnCHMP7 not only interacts with ESCRT
III subunits SNF7.2 (CHMP4B), but also with VPS2.2 and CHMP1B. As expected,
microarray analysis revealed that the expression of ESCRT transport genes is
significantly affected. Additionally, the expression of some genes that are
involved in senescence, protein synthesis and protein degradation is also altered
in BnCHMP7-overexpressing plants. Taken together, BnCHMP7 encodes an endosome
localized protein, which causes dwarfism and leaf senescence as an ESCRT-III
related component.
PMID- 27497742
TI - Agrobacterium rhizogenes rolB gene affects photosynthesis and chlorophyll content
in transgenic tomato (Solanum lycopersicum L.) plants.
AB - Insertion of Agrobacterium rhizogenes rolB gene into plant genome affects plant
development, hormone balance and defence. However, beside the current research,
the overall transcriptional response and gene expression of rolB as a modulator
in plant is unknown. Transformed rolB tomato plant (Solanum lycopersicum L.)
cultivar Tondino has been used to investigate the differential expression
profile. Tomato is a well-known model organism both at the genetic and molecular
level, and one of the most important commercial food crops in the world. Through
the construction and characterization of a cDNA subtracted library, we have
investigated the differential gene expression between transgenic clones of rolB
and control tomato and have evaluated genes specifically transcribed in
transgenic rolB plants. Among the selected genes, five genes encoding for
chlorophyll a/b binding protein, carbonic anhydrase, cytochrome b6/f complex Fe-S
subunit, potassium efflux antiporter 3, and chloroplast small heat-shock protein,
all involved in chloroplast function, were identified. Measurement of
photosynthesis efficiency by the level of three different photosynthetic
parameters (Fv/Fm, rETR, NPQ) showed rolB significant increase in non
photochemical quenching and a, b chlorophyll content. Our results point to
highlight the role of rolB on plant fitness by improving photosynthesis.
PMID- 27497743
TI - Pulmonary Rehabilitation as a Mechanism to Reduce Hospitalizations for Acute
Exacerbations of COPD: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Acute exacerbation of COPD (AECOPD) has a significant impact on
health-care use, including physician visits and hospitalizations. Previous
studies and reviews have shown that pulmonary rehabilitation (PR) has many
benefits, but the effect on hospitalizations for AECOPD is inconclusive. METHODS:
A literature search was carried out to find studies that might help determine,
using a meta-analysis, the impact of PR on AECOPD, defined as unscheduled or
emergency hospitalizations and ED visits. Cohort studies and randomized
controlled trials (RCTs) reporting hospitalizations for AECOPD as an outcome were
included. Meta-analyses compared hospitalization rates between eligible PR
recipients and nonrecipients before and after rehabilitation. RESULTS: Eighteen
studies were included in the meta-analysis. Results from 10 RCTs showed that the
control groups had a higher overall rate of hospitalization than did the PR
groups (control groups: 0.97 hospitalizations/patient-year; 95% CI, 0.67-1.40; PR
groups: 0.62 hospitalizations/patient-year; 95% CI, 0.33-1.16). Five studies
compared admission numbers in the 12 months before and after rehabilitation,
finding a significantly higher admission rate before compared with after (before:
1.24 hospitalizations/patient-year; 95% CI, 0.66-2.34; after: 0.47
hospitalizations/patient-year; 95% CI, 0.28-0.79). The pooled result of three
cohort studies found that the reference group had a lower admission rate compared
with the PR group (0.18 hospitalizations/patient-year; 95% CI, 0.11-0.32 for
reference group vs 0.28 hospitalizations/patient-year; 95% CI, 0.25-0.32 for the
PR group). CONCLUSIONS: Although results from RCTs suggested that PR reduces
subsequent admissions, pooled results from the cohort studies did not, likely
reflecting the heterogeneous nature of individuals included in observational
research and the varying standard of PR programs.
PMID- 27497744
TI - A new concept and finite-element study on dental bond strength tests.
AB - OBJECTIVE: Numerous bond strength tests have been performed on dental adhesion
experiments. Yet, the validity of these bond strength tests is controversial due
to the name (e.g., "shear" or "tensile") may not reflect to the true and complete
stress situation, i.e., assumed uniform shear or uniaxial tensile conditions.
Thus, the aim of this study was to simulate and compare the stress distribution
of and between shear bond strength (SBS), tensile bond strength (TBS), mold
enclosed shear bond strength (ME-SBS) and de novo lever-induced mold-enclosed
shear bond strength (LIME-SBS) tests. METHODS: 3-Dimensional finite element
method (FEM) was used on the dental resin-bonded surfaces (i.e., titanium alloy,
dentine and porcelain) interphased with adhesive layer (thickness 5MUm) to
simulate the mechanical tests. For ME-SBS, both polycarbonate and stainless steel
molds were used. For LIME-SBS, stainless steel levers and molds with lengths of
3mm, 6mm, 12mm, 15mm and 18mm were used. The applied loads on these models were
50N, 100N and 200N. RESULTS: De novo LIME-SBS test was the most optimal
configuration to evaluate "shear" bond strength of adhesive in regards to
providing significantly high and uniform shear stress as well as eliminating
tensile stress at the interface. The conventional SBS test created very high
tensile stress at the load area, whereas the TBS created optimal tensile stress
but shear stress indeed co-exist. The ME-SBS test could also eliminate some of
the tensile stress. Similar stress distributions pattern appeared on the Ti
adhesive models, the dentine-adhesive models and porcelain-adhesive models.
SIGNIFICANCE: None of the bond strength tests could give purely "shear" or
"tensile" bond strength, but LIME-SBS seems to be the best model to evaluate the
bond strength under true "shear" mode.
PMID- 27497745
TI - Mineralogenic characteristics of osteogenic lineage-committed human dental pulp
stem cells following their exposure to a discoloration-free calcium
aluminosilicate cement.
AB - OBJECTIVES: An experimental discoloration-free calcium aluminosilicate cement has
been developed with the intention of maximizing the beneficial attributes of
tricalcium silicate cements and calcium aluminate cements. The present study
examined the effects of this experimental cement (Quick-Set2) on the
mineralogenic characteristics of osteogenic lineage-committed human dental pulp
stem cells (hDPSCs), by comparing the cellular responses with a commercially
available tricalcium silicate cement (white mineral trioxide aggregate
(ProRoot((r)) MTA); WMTA). METHODS: The osteogenic potential of hDPSCs exposed to
the cements was examined using qRT-PCR for osteogenic gene expressions, Western
blot for osteogenic-related protein expressions, alkaline phosphatase enzyme
activity, Alizarin red S staining, Fourier transform infrared spectroscopy and
transmission electron microscopy of extracellular calcium deposits. RESULTS:
Results of the six assays indicated that osteogenic differentiation of hDPSCs was
significantly enhanced after exposure to the tricalcium silicate cement or the
experimental calcium aluminosilicate cement, with the former demonstrating better
mineralogenic stimulation capacity. SIGNIFICANCE: The better osteogenic
stimulating effect of the tricalcium silicate cement on hDPSCs may be due to its
relatively higher silicate content, or higher OH(-) and Ca(2+) release. Further
investigations with the use of in vivo animal models are required to validate the
potential augmenting osteogenic effects of the experimental discoloration-free
calcium aluminosilicate cement.
PMID- 27497746
TI - The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human
microvillus inclusion disease.
AB - Microvillus inclusion disease (MVID) is a life-threatening enteropathy
characterised by malabsorption and incapacitating fluid loss due to chronic
diarrhoea. Histological analysis has revealed that enterocytes in MVID patients
exhibit reduction of microvilli, presence of microvillus inclusion bodies and
intestinal villus atrophy, whereas genetic linkage analysis has identified
mutations in myosin Vb gene as the main cause of MVID. In order to understand the
cellular basis of MVID and the associated formation of inclusion bodies, an
animal model that develops ex utero and is tractable genetically as well as by
microscopy would be highly useful. Here we report that the intestine of the
zebrafish goosepimples (gsp)/myosin Vb (myoVb) mutant shows severe reduction in
intestinal folds - structures similar to mammalian villi. The loss of folds is
further correlated with changes in the shape of enterocytes. In striking
similarity with MVID patients, zebrafish gsp/myoVb mutant larvae exhibit
microvillus atrophy, microvillus inclusions and accumulation of secretory
material in enterocytes. We propose that the zebrafish gsp/myoVb mutant is a
valuable model to study the pathophysiology of MVID. Furthermore, owing to the
advantages of zebrafish in screening libraries of small molecules, the gsp mutant
will be an ideal tool to identify compounds having therapeutic value against
MVID.
PMID- 27497747
TI - A framework for optimal whole-sample histological quantification of neurite
orientation dispersion in the human spinal cord.
AB - BACKGROUND: The complexity of fibre distributions in tissues is an important
microstructural feature, now measurable in vivo by magnetic resonance imaging
(MRI) through orientation dispersion (OD) indices. OD metrics have gained
popularity for the characterisation of neurite morphology, but they still lack
systematic validation. This paper demonstrates a framework for whole-sample
histological quantification of OD in spinal cord specimens, potentially useful
for validating MRI-derived OD estimates. NEW METHOD: Our methodological framework
is based on (i) sagittal sectioning; (ii) Palmgren's silver staining; (iii)
structure tensor (ST) analysis; (iv) directional statistics. Novel elements are
the data-driven optimisation of the spatial scale of ST analysis, and a new
multivariate, weighted directional statistical approach for anisotropy-informed
quantification of OD. RESULTS: Palmgren's silver staining of sagittal spinal cord
sections provides robust visualisation of neuronal elements, enabling OD
quantification. The choice of spatial scale of ST analysis influences OD values,
and weighted directional statistics provide OD maps with high contrast-to-noise.
Segmentation of neurites prior to OD quantification is recommended. COMPARISON
WITH EXISTING METHODS: Our framework can potentially provide OD even in
demyelinating diseases, where myelin-based histology is not suitable. As compared
to conventional univariate approaches, our multivariate weighted directional
statistics improve the contrast-to-noise of OD maps and more accurately describe
the distribution of ST metrics. CONCLUSIONS: Our framework enables practical
whole-specimen characterisation of OD in the spinal cord. We recommend tuning the
scale of ST analysis for optimal OD quantification, as well as neurite
segmentation and weighted directional statistics, of which examples are provided
herein.
PMID- 27497748
TI - Identification of small molecules that improve ATP synthesis defects conferred by
Leber's hereditary optic neuropathy mutations.
AB - Inherited mitochondrial complex I mutations cause blinding Leber's hereditary
optic neuropathy (LHON), for which no curative therapy exists. A specific
biochemical consequence of LHON mutations in the presence of trace rotenone was
observed: deficient complex I-dependent ATP synthesis (CIDAS) and mitochondrial
O2 consumption, proportional to the clinical severity of the three primary LHON
mutations. We optimized a high-throughput assay of CIDAS to screen 1600 drugs to
2, papaverine and zolpidem, which protected CIDAS in LHON cells concentration
dependently. TSPO and cAMP were investigated as protective mechanisms, but a
conclusive mechanism remains to be elucidated; next steps include testing in
animal models.
PMID- 27497750
TI - Thermodynamics of complex coacervation.
AB - Isothermal titration calorimetry has routinely been used to understand the
thermodynamic characteristics of complexation and coacervation. Most commonly,
built-in models that assume independent binding sites have been employed in these
studies. However, the non-covalent nature of interactions and steric effects
accompanying macromolecules require (i) usage of new models such as overlapping
binding sites and Satake-Yang's two-state binding models and (ii) reformed
interpretations of the data as two-stage structuring. Fitting data with these
models, forces driving the interaction of polyelectrolytes with oppositely
charged polyelectrolytes, surfactants, and proteins have been identified as
electrostatics and/or counterion release with possible contributions from
hydrogen bonding and hydrophobic interactions. Additionally, for surfactant
polyelectrolyte coacervation, ITC signals indicated separate regions for
formation of polymer-induced micelles and free micelles. Regardless of the type
of the coacervation system, thermodynamics of coacervation is affected by the
following parameters: pH and ionic strength of the medium, charge density,
molecular weight of the polyelectrolyte, concentration, and mixing order of
macroions. Lastly, we present a brief comparison between ITC on one hand and
surface plasmon resonance or capillary electrophoresis on the other regarding
their application in coacervation.
PMID- 27497749
TI - Children's white blood cell counts in relation to developmental exposures to
methylmercury and persistent organic pollutants.
AB - BACKGROUND: To explore possible markers of developmental immunotoxicity, we
prospectively examined 56 children to determine associations between exposures to
methylmercury and persistent organic pollutants since birth and the comprehensive
differential counts of white blood cells (WBC) at age 5 years. MATERIALS AND
METHODS: Extended differential count included: neutrophils, eosinophils,
basophils, lymphocytes (includingT cells, NK cells, and B cells), and monocytes.
Organochlorine compounds (OCs) including polychlorinated biphenyls (PCBs) and
pesticides, five perfluoroalkyl substances (PFASs), and total mercury (Hg) were
measured in maternal (n=56) and children's blood at 18 months (n=42) and 5 years
(n=54). We constructed latent functions for exposures at three different ages
using factor analyses and applied structural equation models adjusted for
covariates. RESULTS: Prenatal mercury exposure was associated with depleted total
WBC, especially for lymphocytes, where a one standard deviation (SD) increase in
the exposure was associated with a decrease by 23% SD (95% CI: -43, -4) in the
cell count. Prenatal exposure to OCs was marginally associated with decreases in
neutrophil counts. In contrast, the 5-year PFASs concentrations were associated
with higher basophil counts (B=46% SD, 95% CI: 13, 79). Significantly reduced
subpopulations of lymphocytes such as B cells, CD4-positive T helper cells and
CD4 positive recent thymic emigrants may suggest cellular immunity effects and
dysregulation of T-cell mediated immunity. CONCLUSION: Developmental exposure to
environmental immunotoxicants appears to have different impacts on WBC counts in
childhood.
PMID- 27497751
TI - A novel LAMP2 mutation associated with severe cardiac hypertrophy and
microvascular remodeling in a female with Danon disease: a case report and
literature review.
AB - BACKGROUND: Danon disease (DD) is a rare disorder characterized by
cardiomyopathy, intellectual disability, and proximal myopathy. It is caused by
mutations in the LAMP2 gene on X chromosome. Female patients most often present
with late-onset cardiomyopathy and slow disease progression, but early-onset
cases with unfavorable prognosis have been reported. CASE REPORT: We describe the
clinical, pathological, and molecular features of a novel LAMP2 c.453delT
mutation in a female patient with severe hypertrophic cardiomyopathy, Wolff
Parkinson White (WPW) syndrome and rapid progression to heart failure, requiring
heart transplant. Immunohistochemical analysis of LAMP2 in the explanted heart
revealed a mosaic pattern of distribution, with discrete clusters of either
stained or unstained cardiac myocytes, the latter being more frequent in the
septum. These findings paralleled X chromosome inactivation within the
myocardium. Interestingly, multiple foci of microscarring were found on histology
in the Left Ventricle (LV) free wall and septum, in a close spatial relationship
with remodeling and severe stenosis of intramural coronary arterioles.
CONCLUSIONS: Our findings suggest that several features may contribute to the
early and severe cardiac phenotype in female DD patients. The type of mutation
may account for the early disease onset, while both the inhomogeneous
distribution of LAMP2 loss and the presence of microvascular remodeling may be
determinant in the rapid progression to heart failure.
PMID- 27497752
TI - Lumbar artery branches coursing vertically over the intervertebral discs of the
lower lumbar spine: an anatomic study.
AB - PURPOSE: Bleeding from the lumbar artery is a potential complication during the
transpsoas approach to the lower lumbar intervertebral discs. In this anatomic
study, the morphological relationships between the branches of the lumbar artery
and the lower intervertebral disc were investigated to assess the risk of injury
to the branches of the lumbar segmental arteries. METHODS: We studied 88 sites
(86 lumbar arteries) at the third and fourth lumbar vertebrae bilaterally in 22
formalin-fixed cadavers. The branches of the lumbar artery coursing along the
lateral sides of the lower intervertebral disc [muscular branch, anastomotic
branch, and branch supplying the spinal nerve and plexus (BSNP)] and the
iliolumbar artery running upward over the L4-5 disc were identified. Branches
crossing the intervertebral discs vertically were evaluated. RESULTS: Muscular
branches with a lumen structure longer than 2 cm coursed vertically over the
middle third of the intervertebral disc in 3 of 88 sites (3.4 %). Anastomotic
branches ran downward in 13 of 88 (14.8 %), and iliolumbar arteries ran upward on
the posterior third of the lateral sides of the disc in 2 of 88 (2.3 %). BSNPs
ran downward through the posterior third of the disc at 18 of 88 sites (20.5 %).
Overall, the arterial branches coursed vertically over the posterior third of the
lateral sides of the intervertebral discs in approximately 30 % of subjects.
CONCLUSIONS: Lumbar artery branches coursed vertically over the middle third and
the posterior third of the lateral sides of the intervertebral discs in
approximately 3 and 30 % of subjects, respectively.
PMID- 27497753
TI - Measurement of kyphosis and vertebral body height loss in traumatic spine
fractures: an international study.
AB - PURPOSE: To investigate whether wide variations are seen in the measurement
techniques preferred by spine surgeons around the world to assess traumatic
fracture kyphosis and vertebral body height loss (VBHL). METHODS: An online
survey was conducted at two time points among an international community of spine
trauma experts from all world regions. The first survey (TL-survey) focused on
the thoracic, thoracolumbar and lumbar spine, the second survey (C-survey) on the
subaxial cervical spine. Participants were asked to indicate which measurement
technique(s) they used for measuring kyphosis and VBHL. Descriptive statistics,
frequency analysis and the Fisher exact test were used to analyze the responses.
RESULTS: Of the 279 invited experts, 107 (38.4 %) participated in the TL-survey,
and 108 (38.7 %) in the C-survey. The Cobb angle was the most frequently used for
all spine regions to assess kyphosis (55.6-75.7 %), followed by the wedge angle
and adjacent endplates method. Concerning VBHL, the majority of the experts used
the vertebral body compression ratio in all spine regions (51.4-54.6 %). The most
frequently used combination for kyphosis was the Cobb and wedge angles.
Considerable differences were observed between the world regions, while fewer
differences were seen between surgeons with different degrees of experience.
CONCLUSIONS: This study identified worldwide variations in measurement techniques
preferred by treating spine surgeons to assess fracture kyphosis and VBHL in
spine trauma patients. These results establish the importance of standardizing
assessment parameters in spine trauma care, and can be taken into account to
further investigate these radiographic parameters.
PMID- 27497754
TI - Synthesis and characterization of chitosan/curcumin blends based polyurethanes.
AB - In this work, new hexamethylene diisocyanate (HMDI) and hyroxylterminated
polybutadiene (HTPB) based polyurethanes (PUs) were prepared following step
growth polymerization by the introduction of varying mole ratio of chitosan (CH)
and curcumin (CUR). Structural study of blends through infrared spectroscopy
confirmed the incorporation of CH and CUR into the backbone of the PU. The
scanning electron microscopic (SEM) study confirmed the well dispersion of
incorporated chitosan/curcumin and homogeneity of surface of synthesized samples.
Thermogravimetric analysis (TGA) of PU blends indicated a better thermal
stability with 0.25M:0.75M of chitosan to curcumin. Mechanical properties such as
modulus and tensile strength of PU blends were found to be better with higher
contents of chitosan and curcumin. The same extender composition (1mol BDO,
075mol chitosan and 0.25mol curcumin) based PU showed higher substantial of
antimicrobial activity as compared to the all other PUs. On the whole, this work
is actually a step towards the generation of novel biocompatible materials
preferably useful for biomedical applications.
PMID- 27497755
TI - Reliability of 3D gait data across multiple laboratories.
AB - The aim of this study was to analyze the repeatability of gait analysis studies
performed across multiple trials, sessions, and laboratories. Ten healthy
participants (6 male/4 female, mean age of 30, mean BMI of 24kg/m(2)) were
assessed in 3 sessions conducted at each of the three Centers of Excellence for
Amputee Care within the Department of Defense. For each test session, kinematic
and kinetic parameters were collected during five walking trials for each limb.
One independent examiner at each site placed markers on the subjects.
Biomechanical data were collected at two walking speeds: self-selected and Froude
speed. Variability of the gait data was attributed to inter-trial, inter-session,
and inter-lab errors for each subject. These error sources were averaged across
all ten subjects to obtain a pooled error estimate. The kinematic errors were
fairly consistent at the two walking speeds tested. Median inter-lab kinematic
errors were <5.0 degrees (median 2.3 degrees ) for all joint angle measurements.
However, the kinetic error differed significantly between walking speeds. The
median inter-lab kinetic error for the self-selected speed was 0.112Nm/kg (ICR
0.091-0.184) with a maximum of 0.226Nm/kg. The errors were greatly reduced when
the subjects walked at their Froude speed. The median inter-lab error was
0.048Nm/kg (ICR 0.025-0.078, maximum 0.086). These data demonstrate that it is
possible to get reliable data across multiple gait laboratories, particularly
when gait speed is standardized across testing sessions. A key similarity between
sites was the use of identical anatomical segment definitions for the respective
gait models.
PMID- 27497756
TI - Reliability and minimum detectable change of the gait profile score for post
stroke patients.
AB - The objectives of this work were (i) to determine Gait Profile Score (GPS) for
hemiparetic stroke patients, (ii) to evaluate its reliability within and between
sessions, and (iii) to establish its minimal detectable change (MDC). Seventeen
hemiparetic patients (mean age 54.9+/-10.5years; 9 men and 8 women; 6 hemiparetic
on the left side and 11 on the right side; mean time after stroke 6.1+/
3.5months) participated in 2 gait assessment sessions within an interval of 2-7
days. Intra-session reliability was obtained from the intraclass correlation
coefficient (ICC) between the three strides of each session. Inter-session
reliability was estimated by the ICC from the averages of that three strides. GPS
value of non paretic lower limb (NPLL) (13.9+/-2.4 degrees ) was greater than
that of paretic lower limb (PLL) (12.0+/-2.8 degrees ) and overall GPS (GPS_O)
was 13.7+/-2.5 degrees . The Gait Variable Scores (GVS), GPS and GPS_O exhibited
intra-session ICC values between 0.70 and 0.99, suggesting high intra-day
stability. Most of GVS exhibited excellent inter-session reliability (ICC between
0.81 and 0.93). Only hip rotation, hip abduction of PLL exhibited moderate
reliability with ICC/MDC values of 0.57/10.0 degrees and 0.71/3.1 degrees ,
respectively. ICC/MDC values of GPS were 0.92/2.3 degrees and 0.93/1.9 degrees
for PLL and NPLL, respectively. GPS_O exhibited excellent test-retest reliability
(ICC=0.95) and MDC of 1.7 degrees . Given its reliability, the GPS has proven to
be a suitable tool for therapeutic assessment of hemiparetic patients after
stroke.
PMID- 27497757
TI - Precision medicine in acute myeloid leukemia: Hope, hype or both?
AB - Precision medicine is interchangeably used with personalized medicine, genomic
medicine and individualized medicine. Collectively, these terms refer to at least
5 distinct concepts in the context of AML. 1st, using molecular or omics data
(e.g. genomics, epigenomics, transcriptomics, proteomics) to delineate or define
subtypes of AML. 2nd, using these data to select the best therapy for someone
with an AML subtype, such as a person with a FLT3-mutation. 3rd, using these data
to monitor therapy-response such as measurable residual disease [MRD]-testing.
4th, using results of MRD-testing to select from amongst therapy-options such as
additional chemotherapy or a haematopoietic cell transplant. And 5th, using these
data to identify persons with hereditary forms of AML with potential therapy and
surveillance implications. Here, we review these 5 conceptions and delineate
where precision medicine is likely to afford greatest hope and where instead our
rhetoric may constitute hype.
PMID- 27497758
TI - Yeast cells immobilized in spherical gellan particles cross-linked with magnesium
acetate.
AB - In this paper we report on the production of microbioreactors using ionically
cross-linked gellan containing immobilized yeast cells with potential application
in glucose fermentation. Cross-linking was achieved through a novel extrusion
process in capillary by ionotropic gelation under the action of magnesium
acetate. Compared to commonly used methods, this provides a host of practical
advantages. The particles were physico-chemically and morphologically
characterized as their mechanical stability, behavior in aqueous media, and bio
catalytic activity are influenced by the amount of cross-linker used. This
demonstrated their ability to be reused in a large number of fermentation cycles
without losing their bio-catalytic activity. Our results are wholly comparable
with the behavior of free yeast. We show that fermentation cycles can succeed
either immediately or at variable intervals, ensuring high yields of glucose
transformation, comparable-if not superior-to results currently obtained using
free yeast.
PMID- 27497759
TI - Development of fluorescence expression tools to study host-mycoplasma
interactions and validation in two distant mycoplasma clades.
AB - Fluorescence expression tools for stable and innocuous whole mycoplasma cell
labelling have been developed. A Tn4001-derivative mini-transposon affording
unmarked, stable mutagenesis in mycoplasmas was modified to allow the
constitutive, high-level expression of mCherry, mKO2 and mNeonGreen. These tools
were used to introduce the respective fluorescent proteins as chromosomal tags in
the phylogenetically distant species Mycoplasma mycoides subsp. mycoides and
Mycoplasma bovis. The production, selection and characterisation of fluorescent
clones were straightforward and resulted in the unprecedented observation of red
and green fluorescent mycoplasma colonies in the two species, with no apparent
cytotoxicity. Equivalent fluorescence expression levels were quantified by flow
cytometry in both species, suggesting that these tools can be broadly applied in
mycoplasmas. A macrophage infection assay was performed to assess the usefulness
of mNeonGreen-expressing strains for monitoring mycoplasma infections, and
notably cell invasion. The presence of fluorescent mycoplasmas inside live
phagocytic cells was detected and quantified by flow cytometry and corroborated
by confocal microscopy, which allowed the identification of individual
mycoplasmas in the cytoplasm of infected cells. The fluorescence expression tools
developed in this study are suitable for host-pathogen interaction studies and
offer innumerable perspectives for the functional analysis of mycoplasmas both in
vitro and in vivo.
PMID- 27497760
TI - Identification and characterization of polydimethylsiloxane-binding peptides
(PDMS-tag) for oriented immobilization of functional protein on a PDMS surface.
AB - In this study we focused on identifying and characterizing polydimethylsiloxane
binding peptides (PDMS-tags) that show a strong binding affinity towards a PDMS
surface. Three kinds of E. coli host proteins (ELN, OMC and TPA) that were
preferentially adsorbed onto a PDMS surface were identified from the E. coli cell
lysate via 2-D electrophoresis and MALDI TOF MS. Digestion of these PDMS-binding
proteins by 3 types of proteases (trypsin, chymotrypsin and V8 protease) resulted
in the production of a wide variety of peptide fragments with different amino
acid biases. Nine types of peptide fragments showing binding affinities to a PDMS
surface were identified, and they were genetically fused at the C-terminal region
of glutathione S-transferase (GST). The adsorption kinetics of peptide-fused GSTs
to a PDMS surface were evaluated using a quartz crystal microbalance (QCM) sensor
equipped with a sensor chip coated with a PDMS thin film. Consequently, all GSTs
fused with the peptides adsorbed at a level higher than that of wild-type GST. In
particular, the adsorption levels of GSTs fused with ELN-V81, TPA-V81, and OMC
V81 peptides were 8- to 10-fold higher than that of the wild-type GST. These
results indicated that the selected peptides possessed a strong binding affinity
towards a PDMS surface even in cases where they were introduced to the C-terminal
region of a model protein. The remaining activities of GSTs with PDMS-binding
peptides were also greater than that of the wild-type GST. Almost a third (30%)
of enzymatic activity was maintained by genetic fusion of the peptide ELN-V81,
compared with only 1.5% of wild-type GST in the adsorption state. Thus, the PDMS
binding peptides (PDMS-tags) identified in this study will be considerably useful
for the site-specific immobilization of functional proteins to a PDMS surface,
which will be a powerful tool in the fabrication of protein-based micro-reactors
and biosearation chips.
PMID- 27497761
TI - Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through
an Inverse Relationship Between Androgen Receptor Activity and Immune Response.
AB - BACKGROUND: Novel therapies for men with castration-resistant prostate cancer
(CRPC) are needed, particularly for cancers not driven by androgen receptor (AR)
activation. OBJECTIVES: To identify molecular subgroups of PC bone metastases of
relevance for therapy. DESIGN, SETTING, AND PARTICIPANTS: Fresh-frozen bone
metastasis samples from men with CRPC (n=40), treatment-naive PC (n=8), or other
malignancies (n=12) were characterized using whole-genome expression profiling,
multivariate principal component analysis (PCA), and functional enrichment
analysis. Expression profiles were verified by reverse transcription-polymerase
chain reaction (RT-PCR) in an extended set of bone metastases (n=77) and compared
to levels in malignant and adjacent benign prostate tissue from patients with
localized disease (n=12). Selected proteins were evaluated using
immunohistochemistry. A cohort of PC patients (n=284) diagnosed at transurethral
resection with long follow-up was used for prognostic evaluation. RESULTS AND
LIMITATIONS: The majority of CRPC bone metastases (80%) was defined as AR-driven
based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1,
HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were
non-AR-driven. Functional enrichment analysis indicated high metabolic activity
and low immune responses in AR-driven metastases. Accordingly, infiltration of
CD3+ and CD68+ cells was lower in AR-driven than in non-AR-driven metastases, and
tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear
AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A,
TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant
prostate tissue and bone metastases of other origins. In primary PC, low HLA
class I ABC immunoreactivity was associated with high Gleason score, bone
metastasis, and short cancer-specific survival. Limitations include the limited
number of patients studied and the single metastasis sample studied per patient.
CONCLUSIONS: Most CRPC bone metastases show high AR and metabolic activities and
low immune responses. A subgroup instead shows low AR and metabolic activities,
but high immune responses. Targeted therapy for these groups should be explored.
PATIENT SUMMARY: We studied heterogeneities at a molecular level in bone
metastasis samples obtained from men with castration-resistant prostate cancer.
We found differences of possible importance for therapy selection in individual
patients.
PMID- 27497763
TI - Re: Efficacy of High-Intensity Local Treatment for Metastatic Urothelial
Carcinoma of the Bladder: A Propensity Score-Weighted Analysis from the National
Cancer Data Base.
PMID- 27497762
TI - Impact of Enzalutamide Compared with Bicalutamide on Quality of Life in Men with
Metastatic Castration-resistant Prostate Cancer: Additional Analyses from the
TERRAIN Randomised Clinical Trial.
AB - BACKGROUND: Improving health-related quality of life (HRQoL) is an important goal
in metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To examine
the impact of enzalutamide versus bicalutamide on HRQoL in mCRPC. DESIGN,
SETTING, AND PARTICIPANTS: TERRAIN is a multinational, phase 2, randomised,
double-blind study in asymptomatic/mildly symptomatic men with mCRPC
(ClinicalTrials.gov, NCT01288911). Patients were randomised (1:1) via an
interactive voice and web response system to enzalutamide 160mg/d (n=184) or
bicalutamide 50mg/d (n=191), with androgen deprivation therapy. OUTCOME
MEASUREMENTS AND STATISTICAL ANALYSIS: HRQoL was assessed using Functional
Assessment of Cancer Therapy-Prostate (FACT-P), European Quality of Life 5-Domain
Scale (EQ-5D), and Brief Pain Inventory, Short-form questionnaires every 12 wk.
Primary and secondary analyses utilised mixed models for repeated measures and
pattern mixture models, respectively. RESULTS AND LIMITATIONS: At 61 wk, 84 (46%)
enzalutamide and 39 (20%) bicalutamide patients in the study were assessed. At 61
wk, changes from baseline favoured enzalutamide versus bicalutamide on three FACT
P domains in mixed models for repeated measures analyses and seven in pattern
mixture models analyses. There were no differences in changes for EQ-5D
index/visual analogue scale scores. Risk of first deterioration was lower with
enzalutamide for FACT-P total (hazard ratio: 0.64, 95% confidence interval: 0.46
0.89, p=0.007), FACT-G total (hazard ratio: 0.70, 95% confidence interval: 0.50
0.98, p=0.04), PCS pain (hazard ratio: 0.74, 95% confidence interval: 0.54-1.00,
p=0.048), and EQ-5D index (hazard ratio: 0.66, 95% confidence interval: 0.47
0.93, p=0.02) scores versus bicalutamide. Brief Pain Inventory, Short-form scores
increased in both groups. There was no difference in time-to-pain progression.
Study limitations include the exploratory nature of the HRQoL analyses, lack of
multiple comparisons corrections, and unknown effects of anxiety/depression on
HRQoL. CONCLUSIONS: In patients with asymptomatic/mildly symptomatic mCRPC,
enzalutamide provides HRQoL benefit versus bicalutamide. PATIENT SUMMARY:
Enzalutamide treatment was associated with better health-related quality of life
in several domains versus bicalutamide in asymptomatic/mildly symptomatic
metastatic castration-resistant prostate cancer. This likely relates to
previously reported lower rates of symptomatic disease progression.
PMID- 27497765
TI - Evaluation of mutagenic, recombinogenic and carcinogenic potential of (+)-usnic
acid in somatic cells of Drosophila melanogaster.
AB - The main of this study was to evaluate the mutagenic and carcinogenic potential
of (+) - usnic acid (UA), using Somatic Mutation and Recombination Test (SMART)
and the test for detecting epithelial tumor clones (wts) in Drosophila
melanogaster. Larvae from 72 +/- 4 h from Drosophila were fed with UA (5.0, 10.0
or 20.0 mM); urethane (10.0 mM) (positive control); and solvent (Milli-Q water,
1% Tween-80 and 3% ethanol) (negative control). ST cross produced increase in
total mutant spots in the individuals treated with 5.0, 10.0 or 20.0 mM of UA. HB
cross produced spot frequencies in the concentration of 5.0 mM that were higher
than the frequency for the same concentration in the ST cross. In the highest
concentrations the result was negative, which means that the difference observed
can be attributed, in part, to the high levels of P450, suggesting that
increasing the metabolic capacity maximized the toxic effect of these doses. In
the evaluation of carcinogenesis using the wts test, the results obtained for the
same concentrations of UA show a positive result for the presence of tumors when
compared to the negative control. We conclude that UA has recombinogenic,
mutagenic and carcinogenic effects on somatic cells in D. melanogaster.
PMID- 27497764
TI - Prioritization of pesticides based on daily dietary exposure potential as
determined from the SHEDS model.
AB - A major pathway for exposure to many pesticides is through diet. The objectives
were to rank pesticides by comparing their calculated daily dietary exposure as
determined by EPA's Stochastic Human Exposure and Dose Simulation (SHEDS) to
single pesticides for different age groups to acceptable daily intakes (ADI),
characterize pesticide trends in exposures over different time periods, and
determine commodities contributing to pesticide exposures. SHEDS was applied,
using Pesticide Data Program (PDP) (1991-2011) and pesticide usage data on crops
from USDA combined with NHANES dietary consumption data, to generate exposure
estimates by age group. ADI data collected from EPA, WHO, and other sources were
used to rank pesticides based on relativeness of the dietary exposure potential
to ADI by age groups. Sensitivity analysis provided trends in pesticide
exposures. Within SHEDS, commodities contributing the majority of pesticides with
greatest exposure potential were determined. The results indicated that the
highest ranking pesticides were methamidophos and diazinon which exceeded 100% of
the ADI. Sensitivity analysis indicated that exposure to methamidophos, diazinon,
malathion, ethion and formetanate hydrochloride had a marked decrease from 1991
1999 to 2000-2011. Contributions analysis indicated that apples, mushroom,
carrots, and lettuce contributed to diazinon exposure. Beans and pepper
contributed to methamidophos exposure.
PMID- 27497766
TI - Patulin and ochratoxin A co-occurrence and their bioaccessibility in processed
cereal-based foods: A contribution for Portuguese children risk assessment.
AB - Patulin (PAT) and ochratoxin A (OTA) are well known enteropathogenic mycotoxins
that are present in several foodstuffs. Processed cereal-based foods are among
the first solid foods eaten by children, a particularly vulnerable population
group. There is a lack of knowledge related to the co-occurrence of PAT and OTA
in food intended for children consumption and their potential interactions during
the digestion process. The present study aims to evaluate, for the first time,
the co-occurrence of PAT and OTA in processed cereal-based foods for children
consumption, the bioaccessibility of these two mycotoxins, and the contribution
of the bioaccessibility data for human health risk assessment. PAT and OTA
incidence were 75% and 50%, respectively. These mycotoxins co-occurred in 40% of
analysed samples. Bioaccessibility assays revealed mean values of 52% and 56% for
PAT, alone and combined with OTA; and 100% and 106% for OTA, alone and combined
with PAT. Considering the human health risk assessment, and taking into account
the co-occurrence and the bioaccessibility results, this study indicates a
tolerable exposure to these mycotoxins representing a low risk for Portuguese
children. The present work reinforces the importance of a holistic approach for
risk assessment which gathers data from occurrence, exposure and
bioaccessibility.
PMID- 27497767
TI - Reducing Opioid Misuse: Evaluation of a Medicaid Controlled Substance Lock-In
Program.
AB - : Opioid misuse, abuse, and overdose are a rapidly growing public health
epidemic. Medicaid Lock-In Programs (MLIPs) are designed to prevent
overutilization of controlled substances by Medicaid patients. However, despite
widespread use, there is little information on their effect. Using North Carolina
(NC) Medicaid claims data from October 2008 through June 2013, we examined
changes in Medicaid-reimbursed opioid prescriptions by patients enrolled in NC's
MLIP. We used mixed effects models to examine the effect of MLIP enrollment on
monthly opioid claims, number of pharmacies, total days' supply, total units (ie,
pills), and total Medicaid payments for opioids. In our sample of 6,148 MLIP
patients, the odds of having any opioid claim in a given month was 84% lower
during MLIP enrollment relative to the period before enrollment (odds ratio =
.16). MLIP enrollment also corresponded with a reduction in monthly number of
opioid prescriptions by 1.13, monthly number of pharmacies by .61, and monthly
Medicaid expenditures by $22.78. Although MLIPs may constitute a successful
component of comprehensive efforts to reduce the potential overutilization of
opioids, care should be taken to ensure that programs such as MLIPs do not
constrain patients' legitimate needs for analgesic medications. PERSPECTIVE:
Enrollment in NC's MLIP reduced the likelihood that patients would present a
claim for an opioid prescription, and the number of opioid prescriptions patients
secured each month. MLIPs may constitute a successful strategy for reducing the
misuse, abuse, and diversion of prescription opioids. However, further research
is needed to examine the program's potential unintended consequences.
PMID- 27497769
TI - Child and Family Antecedents of Pain During the Transition to Adolescence: A
Longitudinal Population-Based Study.
AB - : Pediatric persistent pain is associated with poorer physical and psychosocial
functioning in children, as well as immediate and long-term societal costs. Onset
typically occurs in early adolescence, suggesting that late childhood is a key
window for identifying potential intervention targets before pain symptoms become
entrenched. This study used population-based data from the Longitudinal Study of
Australian Children (n = 3,812) and adopted a biopsychosocial and ecological
systems approach to investigate child, family, and sociodemographic factors
associated with pain problems in children transitioning to adolescence. The
prevalence of at least weekly parent-reported pain in the study sample was
approximately 5% at 10 to 11 years of age, and pain continued at 12 to 13 years
of age for 40% of these children. Key factors at 10 to 11 years that uniquely
predicted parent-reported pain problems at 12 to 13 years were frequency of
previous pain (1-3 times weekly: odds ratio [OR] = 7.49; 95% confidence interval
[CI], 4.3-13.0; 4-7 times weekly: OR = 17.8; 95% CI, 8.7-36.5) and sleep
difficulties (OR = 1.86; 95% CI, 1.16-2.97). This study highlights the importance
of early intervention for persistent pain in childhood, because pain complaints
in late childhood tend to persist into early adolescence. PERSPECTIVE: This
article used a biopsychosocial and ecological systems approach to understanding
predictors of pain problems during the transition to adolescence within a
nationally representative community-based cohort. Sleep difficulties at 10 to 11
years uniquely predicted pain at ages 12 to 13 years, suggesting that early
intervention using sleep interventions may be a promising direction for future
research.
PMID- 27497768
TI - Involvement of Opioid Receptors and alpha2-Adrenoceptors in Inhibitory Pain
Modulation Processes: A Double-Blind Placebo-Controlled Crossover Study.
AB - : In healthy humans, high-frequency electrical stimulation (HFS) of the forearm
not only evokes local signs of central sensitization but also triggers broader
ipsilateral inhibitory influences on pain akin to a lateralized form of
conditioned pain modulation. Paradoxically, some of these inhibitory influences
are augmented by alpha2-adrenoceptor blockade. To determine whether opioid
peptides mediate inhibitory effects after HFS, the opioid receptor antagonist
naltrexone was coadministered orally with the alpha2-adrenoceptor antagonist
yohimbine in 16 healthy women in a double-blind placebo-controlled crossover
study. In each session, mechanical sensitivity in the forearms and forehead was
assessed before and after HFS. In addition, pain ratings to electrical
stimulation of HFS-treated or control sites in the forearm were assessed during
and after painful stimulation of each temple. Unlike yohimbine alone, the
naltrexone with yohimbine combination blocked analgesia evoked by HFS in the
ipsilateral forehead to blunt pressure, and opposed the ipsilateral inhibitory
effect of pain in the temple on electrically-evoked pain at the HFS-treated site
in the forearm. These findings imply involvement of opioid peptides in an
ipsilateral analgesic response that complements the more generalized form of
conditioned pain modulation. Opioid mediation of this ipsilateral analgesic
response appears to override opposing alpha2-adrenoceptor effects. PERSPECTIVE:
HFS not only evokes local signs of central sensitization but also triggers a
broader ipsilateral antinociceptive mechanism mediated by opioid receptors.
Dysfunction of this lateralized pain modulation process might contribute to
painful unilateral disorders such as migraine or complex regional pain syndrome.
PMID- 27497770
TI - SCN1A Mutation or Cross Talk? The Connection Between the Heart and Brain.
PMID- 27497771
TI - Suicide Attempts in Ilam Province, Western Iran, 2010-2014: A Time Trend Study.
AB - BACKGROUND: Suicide has become an increasingly widespread form of morbidity in
the developing countries. There has been an increasing trend in morbidity and
mortality due to suicide in Iran over the past few decades. This study surveyed
attempts and completed suicide over a 5-year period. METHODS: Through a cross
sectional study, overall identified suicides by systematic registration suicide
data (SRSD) in Ilam Province, western Iran from 21 March 2010 to 11 December 2014
were enrolled. Multiple logistic regression analysis was used for measuring the
association between the risk factors of interest and suicide. The statistical
software package was Stata 11.2. RESULTS: A Suicide attempts have slightly
increased in Ilam during 2010-2014, during which, 6,818 attempted suicides
occurred of which 546 were completed. The odds of completed suicide was higher
among older age groups than younger ones so that the crude OR estimates of
completed suicide among people aged 50 to 59 yr against people aged <20 yr was
(OR=6.99; 95% CI: 3.02, 11.07). The crude and adjusted odds ratio (OR) estimates
of completed suicide in males against females were (OR=3.22; 95% CI: 2.58, 3.93)
and (OR=3.66; 95% CI: 3.03, 4.11), respectively. Significant excess risk also
appeared with academic against illiterate attempters (OR=2.31; 95% CI: 1.35,
3.95). Results showed no increasing trend in the suicide method. Some methods
such as self-immolation had decreasing trend over time, although it was not
statistically significant (P=0.089). CONCLUSIONS: We observed the variety of
suicide risk factors that calls for more diversity in preventative programs.
Distribution of suicide methods is diverse across the period of the study.
PMID- 27497772
TI - Helicobacter Pylori Infection in Children with Type 1 Diabetes Mellitus: A Case
Control Study.
AB - BACKGROUND: Helicobacter pylori infection is one of the most common chronic
bacterial infections. There is challenge on the real rate of prevalence of H.
pylori in diabetic patients. This study was done to assess the prevalence of H.
pylori infection in children suffering from type 1 insulin-dependent diabetes
mellitus. METHODS: In this case-control study, 80 diabetic patients (as the
target group) refer to the Endocrinology Clinic of Tabriz Educational and
Treatment Center, Tabriz northwestern Iran and 80 non-diabetic patients (as the
control group) from the group of children referring to the GI Clinic of the same
center were enrolled in 2012 and 2013. Then H. pylori infection was assessed in
two groups using measuring antibody (IgG) and stool antigen (HpSA). RESULTS: H.
pylori infection tests were positive in 48 (60%) diabetic patients and in 32
(40%) in non-diabetic patients (P=0.030). There was a meaningful correlation
between the frequency of H. pylori and the longer the duration of diabetes
(P<0.001). No correlation was seen between H. pylori infection and other factors
such as age of the patients (P=0.840), HbA1C level (P=0.312), age at which
diabetes was diagnosed (P=0.800), average daily dosage of insulin (P=0.232), and
presence of GI symptoms (P=0.430). CONCLUSIONS: Type 1 diabetic children
especially cases with the longer duration of diabetes, are at risk acquiring H.
pylori infection. Therefore, screening of H. pylori infection is helpful on the
follow up of these patients.
PMID- 27497773
TI - Predictors of Adherence to Type2 Diabetes Medication.
AB - BACKGROUND: Despite the effectiveness of drug therapy in diabetes management high
rates of poor adherence persist. The purpose of this study was to determine the
factors influencing the medication adherence and dietary regiment in type2
diabetic patients. METHODS: This cross sectional study was conducted on 300 type2
diabetic patients referred to General Internal Medicine Clinic, Yazd Shohdaye
Kargar Hospital,Yazd City, central Iran between September and December 2013. Each
consented participant was interviewed by a trained study member using a
questionnaire in three sections: Socio-demographic questions, self-reported
Morisky medication adherence scale and Disease and medication beliefs Patient's
questionnaire. Multivariable logistic regression model was developed to identify
independent predictors of poor adherence. P<0.05 was considered statistically
significant. RESULTS: Patients had diabetes for an average of 8.87 (SD: 6.0) yr
with a mean age of 58.22 (SD: 10.27) yr. Totally, 101(33.7%) of the patients
reported poor adherence with their diabetes medication. In multivariate analyses,
good familial support (OR=0.11; 0.03, 0.37), and tendency to consume sweets
(OR=1.21; 1.05, 1.39), belief about medication (OR=0.02; 0.018, 0.07) and
tendency to consume vegetables (OR=0.75; 0.65, 0.88) were considered as
predictive factors for poor adherence. CONCLUSIONS: Familial support, belief
about medication, tendency to consume sweets and vegetables are logical goals for
educational interventions to modify diabetes self-management.
PMID- 27497774
TI - Analysis of the Factors Affecting the Interval between Blood Donations Using Log
Normal Hazard Model with Gamma Correlated Frailties.
AB - BACKGROUND: Time to donating blood plays a major role in a regular donor to
becoming continues one. The aim of this study was to determine the effective
factors on the interval between the blood donations. METHODS: In a longitudinal
study in 2008, 864 samples of first-time donors in Shahrekord Blood Transfusion
Center, capital city of Chaharmahal and Bakhtiari Province, Iran were selected
by a systematic sampling and were followed up for five years. Among these
samples, a subset of 424 donors who had at least two successful blood donations
were chosen for this study and the time intervals between their donations were
measured as response variable. Sex, body weight, age, marital status, education,
stay and job were recorded as independent variables. Data analysis was performed
based on log-normal hazard model with gamma correlated frailty. In this model,
the frailties are sum of two independent components assumed a gamma distribution.
The analysis was done via Bayesian approach using Markov Chain Monte Carlo
algorithm by OpenBUGS. Convergence was checked via Gelman-Rubin criteria using
BOA program in R. RESULTS: Age, job and education were significant on chance to
donate blood (P<0.05). The chances of blood donation for the higher-aged donors,
clericals, workers, free job, students and educated donors were higher and in
return, time intervals between their blood donations were shorter. CONCLUSIONS:
Due to the significance effect of some variables in the log-normal correlated
frailty model, it is necessary to plan educational and cultural program to
encourage the people with longer inter-donation intervals to donate more
frequently.
PMID- 27497775
TI - Restrictive Pattern of Pulmonary Symptoms among Photocopy and Printing Workers: A
Retrospective Cohort Study.
AB - BACKGROUND: According to the growth of photocopier usage in workplaces, the
potential risk of occupational exposure to the airborne chemicals has been raised
up. Hence, monitoring the photocopy worker's respiratory functions seems to be
necessary. We aimed to evaluate the respiratory health on photocopy and printing
workers so that a reliable description can be made about their occupational
hygiene. METHODS: This study was performed in Shiraz, southwest Iran in 2014 and
a group of 150 photocopy and printing workers were surveyed as exposed group in
addition to a group of 114 office staff as unexposed group. The respiratory
standard questionnaire was used to evaluate the prevalence of respiratory
symptoms among the selected staff. Pulmonary function indexes including VC, FVC,
FEV1 and the FEV1/FVC ratio were calculated. Finally, t-test, Chi Square and
multiple logistic regressions were conducted. RESULTS: VC, FVC and FEV1 in
photocopy and printing workers were lower than the unexposed group of which these
differences for FVC and FEV1 were statistically significant (P<0.05). Moreover,
the prevalence of all respiratory symptoms, except the shortness of breath, in
exposed group was more than the unexposed group and the prevalence of coughing
and wheezing was statistically significant (P<0.05). There was a significant
difference in respiratory symptoms (cough and wheezing) between two groups after
controlling for confounding variables, OR: 2.61 (95% CI: 1.21, 5.62) and 2.92
(95% CI: 1.25, 6.84), respectively. CONCLUSIONS: The prevalence of excess
respiratory symptoms along with pattern of pulmonary restrictive sings in
photocopy and printing workers revealed that the workplace conditions can result
in occupational respiratory diseases.
PMID- 27497776
TI - Integrating the Ergonomics Techniques with Multi Criteria Decision Making as a
New Approach for Risk Management: An Assessment of Repetitive Tasks -Entropy Case
Study.
AB - BACKGROUND: Nowadays, the health work decision makers need to analyze a huge
amount of data and consider many conflicting evaluation criteria and sub
criteria. Therefore, an ergonomic evaluation in the work environment in order to
the control occupational disorders is considered as the Multi Criteria Decision
Making (MCDM) problem. In this study, the ergonomic risks factors, which may
influence health, were evaluated in a manufacturing company in 2014. Then entropy
method was applied to prioritize the different risk factors. METHODS: This study
was done with a descriptive-analytical approach and 13 tasks were included from
total number of employees who were working in the seven halls of an ark opal
manufacturing (240). Required information was gathered by the demographic
questionnaire and Assessment of Repetitive Tasks (ART) method for repetitive task
assessment. In addition, entropy was used to prioritize the risk factors based on
the ergonomic control needs. RESULTS: The total exposure score based on the ART
method calculated was equal to 30.07 +/-12.43. Data analysis illustrated that 179
cases (74.6% of tasks) were in the high level of risk area and 13.8% were in the
medium level of risk. ART- entropy results revealed that based on the weighted
factors, higher value belongs to grip factor and the lowest value was related to
neck and hand posture and duration. CONCLUSIONS: Based on the limited financial
resources, it seems that MCDM in many challenging situations such as control
procedures and priority approaches could be used successfully. Other MCDM methods
for evaluating and prioritizing the ergonomic problems are recommended.
PMID- 27497777
TI - Validating the Heat Stress Indices for Using In Heavy Work Activities in Hot and
Dry Climates.
AB - BACKGROUND: Necessity of evaluating heat stress in the workplace, require
validation of indices and selection optimal index. The present study aimed to
assess the precision and validity of some heat stress indices and select the
optimum index for using in heavy work activities in hot and dry climates.
METHODS: It carried out on 184 workers from 40 brick kilns workshops in the city
of Qom, central Iran (as representative hot and dry climates). After reviewing
the working process and evaluation the activity of workers and the type of work,
environmental and physiological parameters according to standards recommended by
International Organization for Standardization (ISO) including ISO 7243 and ISO
9886 were measured and indices were calculated. RESULTS: Workers engaged in
indoor kiln experienced the highest values of natural wet temperature, dry
temperature, globe temperature and relative humidity among studied sections
(P<0.05). Indoor workplaces had the higher levels of all environmental parameters
than outdoors (P=0.0001), except for air velocity. The wet-bulb globe temperature
(WBGT) and heat stress index (HSI) indices had the highest correlation with other
physiological parameters among the other heat stress indices. Relationship
between WBGT index and carotid artery temperature (r=0.49), skin temperature
(r=0.319), and oral temperature (r=0.203) was statistically significant
(P=0.006). CONCLUSIONS: Since WBGT index, as the most applicable index for
evaluating heat stress in workplaces is approved by ISO, and due to the positive
features of WBGT such as ease of measurement and calculation, and with respect to
some limitation in application of HSI; WBGT can be introduced as the most valid
empirical index of heat stress in the brick workshops.
PMID- 27497778
TI - Comment on: "Estimating Economic Burden of Cancer Deaths Attributable to Smoking
in Iran in 2012".
PMID- 27497779
TI - No effect of anti-inflammatory medication on postprandial and postexercise muscle
protein synthesis in elderly men with slightly elevated systemic inflammation.
AB - BACKGROUND: Based on circulating C-reactive protein (CRP) levels, some
individuals develop slightly increased inflammation as they age. In elderly
inflamed rats, the muscle response to protein feeding is impaired, whereas it can
be maintained by treatment with non-steroidal anti-inflammatory drugs (NSAIDs).
It is unknown whether this applies to elderly humans with increased inflammation.
Thus, the muscle response to whey protein bolus ingestion with and without acute
resistance exercise was compared between healthy elderly individuals and elderly
individuals with slightly increased inflammation+/-NSAID treatment. METHODS:
Twenty-four elderly men (>60years) were recruited. Of those, 14 displayed a
slightly increased systemic inflammation (CRP>2mg/l) and were randomly assigned
to NSAID (Ibuprofen 1800mg/day) or placebo treatment for 1week. The remaining 10
elderly individuals served as healthy controls (CRP<1mg/l). The muscle protein
synthetic response was measured as the fractional synthetic rate (FSR) and p70S6K
phosphorylation-to-total protein ratio. RESULTS: The basal myofibrillar FSR and
the myofibrillar FSR responses to whey protein bolus ingestion with and without
acute resistance exercise were maintained in inflamed elderly compared to healthy
controls (p>0.05) and so was p70S6K phosphorylation. Moreover, NSAID treatment
did not significantly improve the myofibrillar and connective tissue FSR
responses or reduce the plasma CRP level in inflamed, elderly individuals
(p>0.05). CONCLUSION: A slight increase in systemic inflammation does not affect
the basal myofibrillar FSR or the myofibrillar FSR responses, which suggests that
elderly individuals with slightly increased inflammation can benefit from protein
ingestion and resistance exercise to stimulate muscle protein anabolism.
Moreover, the NSAID treatment did not significantly affect the myofibrillar or
connective tissue FSR responses to protein ingestion and acute resistance
exercise.
PMID- 27497781
TI - Multidisciplinary production of interactive environments to support occupational
therapies.
AB - This work focuses on proposing a multidisciplinary production of interactive
environments as a technological support for rehabilitation of people with
physical disabilities attending occupational therapy. Nowadays, some technologies
and methods are used to develop software in order to assist the people who suffer
some kind of physical disability but the physical therapies aren't limited to
only one technique of rehabilitation. Current work promotes establish a
multidisciplinary team such as therapists and technologists, they can collaborate
for the production of interactive environments according the evolution of every
patient's rehabilitation. The performance of current proposal is presented
throughout a related work and a case study with several usability evaluations.
PMID- 27497780
TI - A pilot study of a heuristic algorithm for novel template identification from VA
electronic medical record text.
AB - RATIONALE: Templates in text notes pose challenges for automated information
extraction algorithms. We propose a method that identifies novel templates in
plain text medical notes. The identification can then be used to either include
or exclude templates when processing notes for information extraction. METHODS:
The two-module method is based on the framework of information foraging and
addresses the hypothesis that documents containing templates and the templates
within those documents can be identified by common features. The first module
takes documents from the corpus and groups those with common templates. This is
accomplished through a binned word count hierarchical clustering algorithm. The
second module extracts the templates. It uses the groupings and performs a
longest common subsequence (LCS) algorithm to obtain the constituent parts of the
templates. The method was developed and tested on a random document corpus of 750
notes derived from a large database of US Department of Veterans Affairs (VA)
electronic medical notes. RESULTS: The grouping module, using hierarchical
clustering, identified 23 groups with 3 documents or more, consisting of 120
documents from the 750 documents in our test corpus. Of these, 18 groups had at
least one common template that was present in all documents in the group for a
positive predictive value of 78%. The LCS extraction module performed with 100%
positive predictive value, 94% sensitivity, and 83% negative predictive value.
The human review determined that in 4 groups the template covered the entire
document, with the remaining 14 groups containing a common section template.
Among documents with templates, the number of templates per document ranged from
1 to 14. The mean and median number of templates per group was 5.9 and 5,
respectively. DISCUSSION: The grouping method was successful in finding like
documents containing templates. Of the groups of documents containing templates,
the LCS module was successful in deciphering text belonging to the template and
text that was extraneous. Major obstacles to improved performance included
documents composed of multiple templates, templates that included other templates
embedded within them, and variants of templates. We demonstrate proof of concept
of the grouping and extraction method of identifying templates in electronic
medical records in this pilot study and propose methods to improve performance
and scaling up.
PMID- 27497782
TI - MicroRNA-328, a Potential Anti-Fibrotic Target in Cardiac Interstitial Fibrosis.
AB - BACKGROUND/AIMS: Deregulated myocardial fibrosis is associated with a wide
spectrum of cardiac conditions, being considered one of the major causes for
heart disease. Our study was designed to investigate the role of microRNA-328
(miR-328) in regulating cardiac fibrosis. METHODS: We induced cardiac fibrosis
following MI by occlusion of the left coronary artery in C57BL/6 mice. Real-time
PCR was employed to evaluate the level of miR-328. Masson's Trichrome stain was
used to evaluate the development of fibrosis. Luciferase activity assay was
performed to confirm the miRNA's binding site in the TGFbetaRIII gene. Western
blot analysis was used to examine TGFbetaRIII, p-smad2/3 and TGF-beta1 at protein
level. RESULTS: In this study, we found that miR-328 was significantly
upregulated in the border zone of infarcted myocardium of wild type (WT) mice;
TGFbetaRIII was downregulated whereas TGF-beta1 was upregulated along with
increased cardiac fibrosis. And miR-328 stimulated TGF-beta1 signaling and
promoted collagen production in cultured fibroblasts. We further found that the
pro-fibrotic effect of miR-328 was mediated by targeting TGFbetaRIII.
Additionally, cardiac fibrosis was significantly reduced in infarcted heart when
treated with miR-328 antisense. CONCLUSIONS: These data suggest that miR-328 is a
potent pro-fibrotic miRNA and an important determinant of cardiac fibrosis in
diseased heart.
PMID- 27497783
TI - Evaluation of the toxic potential of coffee wastewater on seeds, roots and
meristematic cells of Lactuca sativa L.
AB - Coffee wastewater (CWW) is an effluent produced through wet processing of coffee
containing high concentration of organic matter, nutrients, salts and also
agrochemicals. It is released directly into the argillaceous soil or into
decantation tanks for later disposal into soils, by fertigation, subsurface
infiltration or superficial draining. However, this practice is not followed by
the monitoring the toxicity potential of this effluent. In this sense, the
present work aimed to evaluate the phytotoxic, cytogenotoxic and mutagenic
potential of CWW on seed germination, root elongation and cell cycle alterations
in the plant model Lactuca sativa L. The effluent (CWW) collected was diluted in
distilled water into six concentrations solutions (1.25%, 1.66%, 2.5%, 5.0%, 10%,
20%). A solution of raw CWW (100%) was also applied. Distilled water was used as
negative control), and the DNA alkylating agent, metilmetano sulfonate (4*10(
4)M) as positive control. Physico-chemical parameters of the CWW was accessed and
it was found that the effluent contained total phenols and inorganic matter in
amounts within the limits established by the National Environment Council
(CONAMA). Nevertheless, the biologicals assays performed demonstrated the
phytotoxicity and cytogenotoxicty of CWW. Seed germination was totally inhibited
after exposure of raw CWW. In addition, a decrease in seed germination speed as
well as in root growth dose-dependently manner was noticed. Moreover, nuclear and
chromosomal alterations were observed in the cell cycle, mostly arising from
aneugenic action.
PMID- 27497784
TI - Assessing the bioremediation potential of algal species indigenous to oil sands
process-affected waters on mixtures of oil sands acid extractable organics.
AB - Surface mining extraction of bitumen from oil sand in Alberta, Canada results in
the accumulation of oil sands process-affected water (OSPW). In attempts to
maximize water recycling, and because its constituents are recognized as being
toxic, OSPW is retained in settling basins. Consequently, research efforts are
currently focused on developing remediation strategies capable of detoxifying
OSPW to allow for eventual release. One potential bioremediation strategy
proposes to utilize phytoplankton native to the Alberta oil sand region to
sequester, break down, or modify the complex oil sands acid extractable organic
(AEO) mixtures in OSPW. Preliminary attempts to quantify changes in total oil
sands AEO concentration in test solutions by ESI-MS following a 14-day algal
remediation period revealed the presence of unknown organic acids in control
samples, likely released by the phytoplankton strains and often of the same
atomic mass range as the oil sands AEO under investigation. To address the
presence of these "biogenic" organic acids in test samples, ESI-MS in MRM mode
was utilized to identify oil sands AEO "marker ions" that were a) present within
the tested oil sands AEO extract and b) unique to the oil sands AEO extract only
(e.g. atomic masses different from biogenic organic acids). Using this approach,
one of the 21 tested algal strains, Stichococcus sp. 1, proved capable of
significantly reducing the AEO marker ion concentration at test concentrations of
10, 30, and 100mgL(-1). This result, along with the accelerated growth rate and
recalcitrance of this algal strain with exposure to oil sands AEO, suggests the
strong potential for the use of the isolated Stichococcus sp. 1 as a candidate
for bioremediation strategies.
PMID- 27497785
TI - Identification of interacting proteins with aryl hydrocarbon receptor in scallop
Chlamys farreri by yeast two hybrid screening.
AB - The aryl hydrocarbon receptor (AhR) belongs to the basic-helix-loop helix (bHLH)
Per-Arnt-Sim (PAS) family of transcription factors. AhR has been known primarily
for its role in the regulation of several drug and xenobiotic metabolizing
enzymes, as well as the mediation of the toxicity of certain xenobiotics,
including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Although the AhR is well
studied as a mediator of the toxicity of certain xenobiotics in marine bivalves,
the normal physiological function remains unknown. In order to explore the
function of the AhR, the bait protein expression plasmid pGBKT7-CfAhR and the
cDNA library of gill from Chlamys farreri were constructed. By yeast two hybrid
system, after multiple screening with the high screening rate medium, rotary
verification, sequencing and bioinformatics analysis, the interactions of the
CfAhR with receptor for activated protein kinase C 1 (RACK1), thyroid peroxidase
like protein (TPO), Toll-like receptor 4(TLR 4), androglobin-like, store-operated
Ca(2+) entry (SocE), ADP/ATP carrier protein, cytochrome b, thioesterase, actin,
ferritin subunit 1, poly-ubiquitin, short-chain collagen C4-like and one
hypothetical protein in gill cells were identified. This study suggests that the
CfAhR played fundamental roles in immune system homeostasis, oxidative stress
response, and in grow and development of C. farreri. The elucidation of these
protein interactions is of much importance both in understanding the normal
physiological function of AhR, and as potential targets for further research on
protein function in AhR interactions.
PMID- 27497786
TI - Pharmacist-based health coaching: A new model of pharmacist-patient care.
AB - This paper describes a provider-patient communication process, which although not
new to health care in general, is new to the pharmacy profession. Health coaching
is a technique that empowers patients to make lasting health behavior changes
that improve overall well-being. It provides patients with health care
implementation options that better suit their lifestyle and abilities. Health
coaching programs have the potential to foster better health outcomes, especially
with patients who are chronically ill or represent an at risk population for
medication non-adherence (e.g. elderly, patients on psychotropic medications).
Other health professions (e.g. nursing and medicine) have had success with the
implementation of health coaching models. For example, nurse coaching is
recognized by the American Nurse Association and recent statistics show 3.1
million nurses in the U.S.A are also trained in nurse coaching. The pharmacy
profession has yet to tap the patient-related benefits of health coaching. This
commentary will discuss (i) The theoretical foundations of health coaching (ii)
Distinctions between health coaching, motivational interviewing and traditional
medication therapy counseling (iii) Training necessary for health coaching; and
(iv) How pharmacists can use health coaching in practice.
PMID- 27497787
TI - Triggering of Suicidal Erythrocyte Death by Psammaplin A.
AB - BACKGROUND/AIMS: Psammaplin A, a natural product isolated from marine sponges,
triggers apoptosis of tumor cells and is thus considered for the treatment of
malignancy. In analogy to apoptosis of nucleated tumor cells, erythrocytes may
enter eryptosis, a suicidal death characterized by cell shrinkage and cell
membrane scrambling with phosphatidylserine translocation to the erythrocyte
surface. Cellular mechanisms stimulating eryptosis include increase of cytosolic
Ca2+ activity ([Ca2+]i), oxidative stress and ceramide. The present study
explored, whether Psammaplin A induces eryptosis and to possibly shed some light
on the underlying mechanisms. METHODS: Phosphatidylserine exposing erythrocytes
were identified utilizing annexin-V-binding, cell volume was estimated from
forward scatter, [Ca2+]i determined utilizing Fluo3-fluorescence, the abundance
of reactive oxygen species (ROS) quantified with DCFDA dependent fluorescence,
and ceramide abundance at the erythrocyte surface detected with specific
antibodies. RESULTS: A 48 hours exposure of human erythrocytes to Psammaplin A (2
8 ug/ml) significantly decreased forward scatter and significantly increased the
percentage of annexin-V-binding cells. Psammaplin A significantly increased Fluo3
fluorescence, the effect of Psammaplin A on annexin-V-binding and forward scatter
was, however, not significantly blunted by removal of extracellular Ca2+.
Psammaplin A significantly increased DCFDA fluorescence and ceramide abundance.
CONCLUSIONS: Psammaplin A triggers cell shrinkage and phospholipid scrambling of
the erythrocyte cell membrane, an effect paralleled by increase of [Ca2+]i,
induction of oxidative stress and enhanced appearance of ceramide.
PMID- 27497788
TI - Variable reporting of functional outcomes and return to play in superior labrum
anterior and posterior tear.
AB - BACKGROUND: Outcomes assessments after superior labrum anterior and posterior
(SLAP) tear/repair are highly varied, making it difficult to draw comparisons
across the literature. This study examined the inconsistency in outcomes
reporting in the SLAP tear literature. We hypothesize that there is significant
variability in outcomes reporting and that although most studies may report
return to play, time to return reporting will be highly variable. METHODS: The
PubMed, Medline, Scopus, and Embase databases were systematically reviewed for
studies from January 2000 to December 2014 reporting outcomes after SLAP
tear/repair. Two reviewers assessed each study, and those meeting inclusion
criteria were examined for pertinent data. Outcomes included objective (range of
motion, strength, clinical examinations, and imaging) and subjective (patient
reported outcomes, satisfaction, activities of daily living, and return to play)
measures. RESULTS: Of the 56 included studies, 43% documented range of motion,
14% reported strength, and 16% noted postoperative imaging. There was significant
variation in use of patient-reported outcomes measures, with the 3 most commonly
noted measures reported in 20% to 55% of studies. Return to play was noted in 75%
of studies, and 23% reported time to return, with greater rates in elite
athletes. Eleven studies (20%) did not report follow-up or noted data with <12
months of follow-up. CONCLUSIONS: The SLAP literature is characterized by
substantial variability in outcomes reporting, with time to return to play noted
in few studies. Efforts to standardize outcomes reporting would facilitate
comparisons across the literature and improve our understanding of the prognosis
of this injury.
PMID- 27497789
TI - Prevalence of asymptomatic rotator cuff tear and their related factors in the
Korean population.
AB - BACKGROUND: No information is available about asymptomatic rotator cuff tears
(RCTs) in the Korean population. This study evaluated the prevalence of rotator
cuff tears without symptoms and their related risk factors. MATERIALS AND
METHODS: The study included 486 volunteers (70.4% female; mean age, 53.1; range,
20-82 years) without any shoulder symptom complaints. Background data, medical
history, clinical self-assessment, and physical examination were recorded. An
ultrasonographic examination was conducted to identify rotator cuff pathology,
but only full-thickness RCTs (FTRCTs) were included for the statistical analysis.
RESULTS: FTRCTs were found in 23 subjects (4.7%) but only in those aged >=49
years. Subjects aged 50-59, 60-69, and >=70 years of age had FTRCT prevalence
rates of 3.5%, 13.3%, and 11.1%, respectively. The prevalence of FTRCTs was
higher in subjects with diabetes (P = .042) and a smoking history (P= .002), but
no differences were noted for the presence of thyroid disease (P = .051). Almost
half of those who had FTRCTs had some pain and limited daily activity that was
not bothersome. After excluding these subjects from the analysis, the prevalence
of asymptomatic FTRCTs decreased to 2.3%. CONCLUSIONS: The prevalence of
asymptomatic FTRCTs was lower than expected. Half of asymptomatic FTRCTs were not
actually symptom free after the clinical and physical assessments. The risk
factors for a FTRCT were age, diabetes, and smoking.
PMID- 27497790
TI - Single cell genomics reveals activation signatures of endogenous SCAR's networks
in aneuploid human embryos and clinically intractable malignant tumors.
AB - Somatic mutations and chromosome instability are hallmarks of genomic aberrations
in cancer cells. Aneuploidies represent common manifestations of chromosome
instability, which is frequently observed in human embryos and malignant solid
tumors. Activation of human endogenous retroviruses (HERV)-derived loci is
documented in preimplantation human embryos, hESC, and multiple types of human
malignancies. It remains unknown whether the HERV activation may highlight a
common molecular pathway contributing to the frequent occurrence of chromosome
instability in the early stages of human embryonic development and the emergence
of genomic aberrations in cancer. Single cell RNA sequencing analysis of human
preimplantation embryos reveals activation of specific LTR7/HERVH loci during the
transition from the oocytes to zygotes and identifies HERVH network signatures
associated with the aneuploidy in human embryos. The correlation patterns'
analysis links transcriptome signatures of the HERVH network activation of the in
vivo matured human oocytes with gene expression profiles of clinical samples of
prostate tumors supporting the existence of a cancer progression pathway from
putative precursor lesions (prostatic intraepithelial neoplasia) to localized and
metastatic prostate cancers. Tracking signatures of HERVH networks' activation in
tumor samples from cancer patients with known long-term therapy outcomes enabled
patients' stratification into sub-groups with markedly distinct likelihoods of
therapy failure and death from cancer. Genome-wide analyses of human-specific
genetic elements of stem cell-associated retroviruses (SCARs)-regulated networks
in 12,093 clinical tumor samples across 29 cancer types revealed pan-cancer
genomic signatures of clinically-lethal therapy resistant disease defined by the
presence of somatic non-silent mutations (SNMs), gene-level copy number changes,
and transcripts and proteins' expression of SCARs-regulated host genes. More than
73% of all cancer deaths occurred in patients whose tumors harbor the SNMs'
signatures. Linear regression analysis of the cancer intractability in the United
States population demonstrated that organ-specific cancer death rates are
directly correlated with the percentages of patients whose tumors harbor the
SNMs' signatures. Present analyses suggest that awakening of SCARs-regulated
stemness networks in differentiated cells is associated with development of
diverse spectrum of genomic aberrations in multiple types of clinically lethal
malignant tumors contributing to emergence of therapy-resistant cancer
phenotypes.
PMID- 27497791
TI - Male Urethral Stricture: American Urological Association Guideline.
AB - PURPOSE: The purpose of this Guideline is to provide a clinical framework for the
diagnosis and treatment of male urethral stricture. MATERIALS AND METHODS: A
systematic review of the literature using the Pubmed, Embase, and Cochrane
databases (search dates 1/1/1990 to 12/1/2015) was conducted to identify peer
reviewed publications relevant to the diagnosis and treatment of urethral
stricture. The review yielded an evidence base of 250 articles after application
of inclusion/exclusion criteria. These publications were used to create the
Guideline statements. Evidence-based statements of Strong, Moderate, or
Conditional Recommendation were developed based on benefits and risks/burdens to
patients. Additional guidance is provided as Clinical Principles and Expert
Opinion when insufficient evidence existed. RESULTS: The Panel identified the
most common scenarios seen in clinical practice related to the treatment of
urethral strictures. Guideline statements were developed to aid the clinician in
optimal evaluation, treatment, and follow-up of patients presenting with urethral
strictures. CONCLUSIONS: Successful treatment of male urethral stricture requires
selection of the appropriate endoscopic or surgical procedure based on anatomic
location, length of stricture, and prior interventions. Routine use of imaging to
assess stricture characteristics will be required to apply evidence based
recommendations, which must be applied with consideration of patient preferences
and personal goals. As scientific knowledge relevant to urethral stricture
evolves and improves, the strategies presented here will be amended to remain
consistent with the highest standards of clinical care.
PMID- 27497792
TI - Standardized Reporting of Microscopic Renal Tumor Margins: Introduction of the
Renal Tumor Capsule Invasion Scoring System.
AB - PURPOSE: Renal tumor enucleation allows for maximal parenchymal preservation.
Identifying pseudocapsule integrity is critically important in nephron sparing
surgery by enucleation. Tumor invasion into and through the capsule may have
clinical implications, although it is not routinely commented on in standard
pathological reporting. We describe a system to standardize the varying degrees
of pseudocapsule invasion and identify predictors of invasion. MATERIALS AND
METHODS: We performed a multicenter retrospective review between 2002 and 2014 at
Indiana University Hospital and Loyola University Medical Center. A total of 327
tumors were evaluated following removal via radical nephrectomy, standard margin
partial nephrectomy or enucleation partial nephrectomy. Pathologists scored
tumors using our i-Cap (invasion of pseudocapsule) scoring system. Multivariate
analysis was done to determine predictors of higher score tumors. RESULTS: Tumor
characteristics were similar among surgical resection groups. Enucleated tumors
tended to have thinner pseudocapsule rims but not higher i-Cap scores. Rates of
complete capsular invasion, scored as i-Cap 3, were similar among the surgical
techniques, comprising 22% of the overall cohort. Papillary histology along with
increasing tumor grade was predictive of an i-Cap 3 score. CONCLUSIONS: A capsule
invasion scoring system is useful to classify renal cell carcinoma pseudocapsule
integrity. i-Cap scores appear to be independent of surgical technique. Complete
capsular invasion is most common in papillary and high grade tumors. Further work
is warranted regarding the relevance of capsular invasion depth as it relates to
the oncologic outcome for local recurrence and disease specific survival.
PMID- 27497793
TI - Patient and clinician perspectives on the outpatient after-visit summary: a
qualitative study to inform improvements in visit summary design.
AB - Objective: We explored patients' and clinicians' perspectives on electronic
health record (EHR)-generated outpatient after-visit summaries (AVSs) to inform
efforts to maximize the document's utility. Materials and Methods: This
qualitative study involved focus groups and semistructured interviews with
patients ( n = 39) and clinicians ( n = 56) in adult primary care practices
serving socioeconomically diverse communities in New York City; Long Island, New
York; and Chicago, Illinois. Focus group and interview transcripts were coded and
analyzed following standard qualitative methods. Results: Core themes included
the use and purpose of the AVS, content modification and prioritization,
formatting improvements, customization, privacy and accuracy concerns, and
clinician workflow concerns. While most patients valued the document as a visit
summary, others considered it a general summary of their health and health care
issues, useful for sharing with family or clinicians even if they had access to
their health records via web portals. Patients expressed a preference for the
order of content items, and many wanted the reasons for medications and referrals
stated. Additionally, some patients were confused by multiple medication lists
indicating started, stopped, and modified medications, and a single "current"
medication list was preferred by both patients and doctors. Concerns were raised
about the risk of violating patient privacy and challenges to clinician workflow.
Discussion: The AVS is valued by patients and clinicians. Both groups have
identified numerous ways it can be improved, but also several obstacles to
improvement and effective use. Conclusion: EHR vendors should work with
stakeholder groups to improve the AVS to ensure that this important communication
device achieves its patient-centered potential.
PMID- 27497794
TI - Context-sensitive decision support (infobuttons) in electronic health records: a
systematic review.
AB - Objective: Infobuttons appear as small icons adjacent to electronic health record
(EHR) data (e.g., medications, diagnoses, or test results) that, when clicked,
access online knowledge resources tailored to the patient, care setting, or task.
Infobuttons are required for "Meaningful Use" certification of US EHRs. We sought
to evaluate infobuttons' impact on clinical practice and identify features
associated with improved outcomes. Methods: We conducted a systematic review,
searching MEDLINE, EMBASE, and other databases from inception to July 6, 2015. We
included and cataloged all original research in any language describing
implementation of infobuttons or other context-sensitive links. Studies
evaluating clinical implementations with outcomes of usage or impact were
reviewed in greater detail. Reviewers worked in duplicate to select articles,
evaluate quality, and abstract information. Results: Of 599 potential articles,
77 described infobutton implementation. The 17 studies meriting detailed review,
including 3 randomized trials, yielded the following findings. Infobutton usage
frequency ranged from 0.3 to 7.4 uses per month per potential user. Usage
appeared to be influenced by EHR task. Five studies found that infobuttons are
used less often than non-context-sensitive links (proportionate usage 0.20-0.34).
In 3 studies, users answered their clinical question in > 69% of infobutton
sessions. Seven studies evaluated alternative approaches to infobutton design and
implementation. No studies isolated the impact of infobuttons on objectively
measured patient outcomes. Conclusions: Weak evidence suggests that infobuttons
can help providers answer clinical questions. Research on optimal infobutton
design and implementation, and on the impact on patient outcomes and provider
behaviors, is needed.
PMID- 27497795
TI - Inviting patients and care partners to read doctors' notes: OpenNotes and shared
access to electronic medical records.
AB - We examined the acceptability and effects of delivering doctors' visit notes
electronically (via OpenNotes) to patients and care partners with authorized
access to patients' electronic medical records. Adult patients and care partners
at Geisinger Health System were surveyed at baseline and after 12 months of
exposure to OpenNotes. Reporting on care partner access to OpenNotes, patients
and care partners stated that they had better agreement about patient treatment
plans and more productive discussions about their care. At follow-up, patients
were more confident in their ability to manage their health, felt better prepared
for office visits, and reported understanding their care better than at baseline.
Care partners were more likely to access and use patient portal functionality and
reported improved communication with patients' providers at follow-up. Our
findings suggest that offering patients and care partners access to doctors'
notes is acceptable and improves communication and patients' confidence in
managing their care.
PMID- 27497796
TI - Opening government health data to the public: benefits, challenges, and lessons
learned from early innovators.
AB - Objective: Government agencies are rapidly developing web portals to proactively
publish "open" data that are searchable, available in nonproprietary formats, and
with unlimited use and distribution rights. In this dynamic environment, we aimed
to understand the experiences of 2 early leaders in open health data, the US
Department of Health and Human Services and the New York State Department of
Health. Materials and Methods: Semistructured interviews with 40 practitioners
and policymakers elicited value propositions, capabilities required for
successful open data programs, and strategies for improving impact and
sustainability. Transcripts were analyzed using a grounded theory approach to
identify common perspectives and divergent viewpoints. Results: Respondents were
optimistic about the value of open data, reporting numerous opportunities to
advance the triple aim of lower costs, improved health care quality, and better
population health. Benefits to agencies include enhanced data quality and more
efficient operations. External benefits include improved health literacy, data
driven changes in health care delivery, consumer engagement, and community
empowerment. Key challenges are resources, cultural resistance, navigating legal
and regulatory issues, and data quality. Discussion: The open data movement will
likely continue, but success requires sustained leadership, resources,
organizational cultural change, promotion of data use, and governance.
Jurisdictions that are initiating open data programs can incorporate these
lessons from early innovators. Conclusions: The open data movement has a bright
future but unknown long-term impact. To maintain momentum, important directions
for the field include reconsidering legal guidance on protecting health data in
the open data era and quantifying the return on investment.
PMID- 27497797
TI - eHealth patient-provider communication in the United States: interest,
inequalities, and predictors.
AB - Objective: Health-related Internet use and eHealth technologies, including online
patient-provider communication (PPC), are continually being integrated into
health care environments. This study aimed to describe sociodemographic and
health- and Internet-related correlates that influence adult patients' interest
in and electronic exchange of medical information with health care providers in
the United States. Methods: Nationally representative cross-sectional data from
the 2014 Health Information National Trends Survey ( N = 3677) were analyzed.
Descriptive statistics and multivariable regression analyses were performed to
examine associations between patient-level characteristics and online PPC
behavior and interests. Results: Most respondents were Internet users (82.8%),
and 61.5% of information seekers designated the Internet as their first source
for health information. Younger respondents (<50 years), Hispanics, those from
higher-income households, and those perceiving access to personal health
information as important were more likely to be interested in online PPC. Despite
varying levels of patient interest, 68.5% had no online PPC in the last year.
However, Internet users (odds ratio, OR = 2.87, 95% CI, 1.35-6.08), college
graduates (OR = 2.92, 95% CI, 1.42-5.99), and those with frequent provider visits
(OR = 1.94, 95% CI, 1.02-3.71) had a higher likelihood of online PPC via email or
fax, while Hispanics and those from higher-income households were 2-3 times more
likely to communicate via text messaging or phone/mobile apps. Conclusion:
Patients' interest in and display of online PPC-related behaviors vary by age,
race/ethnicity, education, income, Internet access/behaviors, and information
type. These findings can inform efforts aimed at improving the use and adoption
of eHealth technologies, which may contribute to a reduction in communication
inequalities and health care disparities.
PMID- 27497798
TI - Biomedical informatics advancing the national health agenda: the AMIA 2015 year
in-review in clinical and consumer informatics.
AB - The field of biomedical informatics experienced a productive 2015 in terms of
research. In order to highlight the accomplishments of that research, elicit
trends, and identify shortcomings at a macro level, a 19-person team conducted an
extensive review of the literature in clinical and consumer informatics. The
result of this process included a year-in-review presentation at the American
Medical Informatics Association Annual Symposium and a written report (see
supplemental data). Key findings are detailed in the report and summarized here.
This article organizes the clinical and consumer health informatics research from
2015 under 3 themes: the electronic health record (EHR), the learning health
system (LHS), and consumer engagement. Key findings include the following: (1)
There are significant advances in establishing policies for EHR feature
implementation, but increased interoperability is necessary for these to gain
traction. (2) Decision support systems improve practice behaviors, but evidence
of their impact on clinical outcomes is still lacking. (3) Progress in natural
language processing (NLP) suggests that we are approaching but have not yet
achieved truly interactive NLP systems. (4) Prediction models are becoming more
robust but remain hampered by the lack of interoperable clinical data records.
(5) Consumers can and will use mobile applications for improved engagement, yet
EHR integration remains elusive.
PMID- 27497799
TI - Comparison of heuristic and cognitive walkthrough usability evaluation methods
for evaluating health information systems.
AB - Objective: There are several user-based and expert-based usability evaluation
methods that may perform differently according to the context in which they are
used. The objective of this study was to compare 2 expert-based methods,
heuristic evaluation (HE) and cognitive walkthrough (CW), for evaluating
usability of health care information systems. Materials and methods: Five
evaluators independently evaluated a medical office management system using HE
and CW. We compared the 2 methods in terms of the number of identified usability
problems, their severity, and the coverage of each method. Results: In total, 156
problems were identified using the 2 methods. HE identified a significantly
higher number of problems related to the "satisfaction" attribute ( P = .002).
The number of problems identified using CW concerning the "learnability"
attribute was significantly higher than those identified using HE ( P = .005).
There was no significant difference between the number of problems identified by
HE, based on different usability attributes ( P = .232). Results of CW showed a
significant difference between the number of problems related to usability
attributes ( P < .0001). The average severity of problems identified using CW
was significantly higher than that of HE ( P < .0001). Conclusion: This study
showed that HE and CW do not differ significantly in terms of the number of
usability problems identified, but they differ based on the severity of problems
and the coverage of some usability attributes. The results suggest that CW would
be the preferred method for evaluating systems intended for novice users and HE
for users who have experience with similar systems. However, more studies are
needed to support this finding.
PMID- 27497801
TI - Surgical Treatment of Displaced Midshaft Clavicle Fractures: Precontoured Plates
Versus Noncontoured Plates.
AB - PURPOSE: To compare the outcomes and complications of open reduction and internal
fixation using precontoured versus noncontoured plates for the treatment of
midshaft clavicle fractures. METHODS: Open reduction and internal fixation using
was performed on 130 patients with a midshaft clavicle fracture. Precontoured
plates were used in 69 cases (group A) and noncontoured plates in 61 cases (group
B). RESULTS: The average follow-up in both groups was approximately 21 months.
There was a significant difference between the 2 groups in mean surgery duration
and blood loss, although Disabilities of the Arm, Shoulder, and Hand and Constant
Murley Shoulder scores at final follow-up were similar. Plate removal was
required in 44.9% (31 of 69) of the precontoured group and 65.6% (40 of 61) of
the noncontoured group. The indication was prominence of the hardware in 27.5%
(19 of 69) of the precontoured group and 54.1% (33 of 61) of the noncontoured. In
both groups, body mass index was lower in patients requiring implant removal
because of hardware prominence. A higher proportion of females in both groups
required implant removal. CONCLUSIONS: Precontoured plates are associated with a
lower rate of hardware removal. Body mass index and gender may be factors that
influence the rate of hardware removal. TYPE OF STUDY/LEVEL OF EVIDENCE:
Therapeutic IV.
PMID- 27497800
TI - Evaluating electronic health record data sources and algorithmic approaches to
identify hypertensive individuals.
AB - OBJECTIVE: Phenotyping algorithms applied to electronic health record (EHR) data
enable investigators to identify large cohorts for clinical and genomic research.
Algorithm development is often iterative, depends on fallible investigator
intuition, and is time- and labor-intensive. We developed and evaluated 4 types
of phenotyping algorithms and categories of EHR information to identify
hypertensive individuals and controls and provide a portable module for
implementation at other sites. MATERIALS AND METHODS: We reviewed the EHRs of 631
individuals followed at Vanderbilt for hypertension status. We developed features
and phenotyping algorithms of increasing complexity. Input categories included
International Classification of Diseases, Ninth Revision (ICD9) codes,
medications, vital signs, narrative-text search results, and Unified Medical
Language System (UMLS) concepts extracted using natural language processing
(NLP). We developed a module and tested portability by replicating 10 of the best
performing algorithms at the Marshfield Clinic. RESULTS: Random forests using
billing codes, medications, vitals, and concepts had the best performance with a
median area under the receiver operator characteristic curve (AUC) of 0.976.
Normalized sums of all 4 categories also performed well (0.959 AUC). The best non
NLP algorithm combined normalized ICD9 codes, medications, and blood pressure
readings with a median AUC of 0.948. Blood pressure cutoffs or ICD9 code counts
alone had AUCs of 0.854 and 0.908, respectively. Marshfield Clinic results were
similar. CONCLUSION: This work shows that billing codes or blood pressure
readings alone yield good hypertension classification performance. However, even
simple combinations of input categories improve performance. The most complex
algorithms classified hypertension with excellent recall and precision.
PMID- 27497802
TI - Estimating Scaphoid Lengths Using Anatomical Measurements in the Wrist.
AB - PURPOSE: In reconstructive surgery of scaphoid nonunions with humpback deformity,
some surgeons recommend restoration of the normal scaphoid length whereas others
overexpand the normal length to ensure carpal realignment and prevent late
collapse. To be able to define overexpansion and investigate which levels of
overexpansion yield optimal clinical results, a precise method for estimating the
original scaphoid length is required. The purpose of this anatomic study was to
investigate the precision of estimating normal scaphoid lengths based on intact
adjacent bone dimensions, compared with using the contralateral scaphoid length.
METHODS: From bilateral computed tomographic scans of 28 healthy wrist pairs, 3
dimensional virtual bone models were created. The left and right scaphoid lengths
were determined at the central axis. The capitate length at the central axis and
the distal radius width served to derive an ipsilateral scaphoid length estimate.
Estimation precision for individual cases was based on the 95% range (+/-1.96 *
SD) of the observed differences between the actual and estimated lengths.
RESULTS: On average, the capitate length was 10% smaller than the scaphoid
length; the radius width was 9% larger. Consequently, we averaged the capitate
length and radius width for ipsilateral estimations. The average difference
between the scaphoid length and the latter ipsilateral estimate was 0.1 mm. The
average contralateral scaphoid length difference was also 0.1 mm. Estimation
precisions, however, were +/-2.2 and +/-1.4 mm, respectively. CONCLUSIONS:
Scaphoid length estimation based on the contralateral scaphoid is more precise
than the estimating scaphoid length using the ipsilateral radius and capitate.
CLINICAL RELEVANCE: Scaphoid overexpansion can be ensured if the restored length
is at least 1.4 mm longer than the contralateral length. This may be valuable
information when establishing a target length for reconstruction and
investigating the consequences of scaphoid overexpansion on clinical function,
such as range of motion, which are currently unknown.
PMID- 27497803
TI - The use of deformable image registration to integrate diagnostic MRI into the
radiotherapy planning pathway for head and neck cancer.
AB - BACKGROUND AND PURPOSE: To assess the accuracy of gross tumour volume (GTV)
delineation for head and neck squamous cell carcinoma (HNSCC) using a diagnostic
position MRI (MRI-D) deformably registered to the planning CT (pCT), by
comparison with a dedicated planning position MRI (MRI-RT). MATERIAL AND METHODS:
Fourteen patients with HNSCC underwent a T1-weighted MRI-D and MRI-RT. A
reference GTV was defined as that delineated on MRI-RT rigidly registered to pCT.
GTVs were delineated on: MRI-D and then registered to pCT by deformable image
registration over the whole image (DIR-whole); MRI-D and then registered to pCT
with rigid registration over a region of interest defined as GTV+3cm (Rigid-ROI);
and on the pCT alone. These were compared using positional metrics to the
reference. RESULTS: GTVs delineated on MRI-D followed by DIR-whole were
significantly more accurate than those delineated on CT alone. The mean Dice
Similarity Coefficient was 0.6 and 0.72 for pCT and DIR-whole respectively. Use
of MRI-D with Rigid-ROI provided no advantage over CT-only delineation.
CONCLUSIONS: Contouring on MRI-RT rigidly registered to pCT should be considered
as the gold standard for HNSCC. In radiotherapy centres lacking a dedicated MRI
RT, the use of an MRI-D with DIR-whole offers a significant advantage for the
accuracy of GTV delineation over contouring on pCT alone.
PMID- 27497804
TI - Comparison of investigator-delineated gross tumour volumes and quality assurance
in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial.
AB - BACKGROUND AND PURPOSE: We performed a retrospective central review of tumour
outlines in patients undergoing radiotherapy in the SCALOP trial. MATERIALS AND
METHODS: The planning CT scans were reviewed retrospectively by a central review
team, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was compared
to the trials team-defined gold standard (gsGTV and gsPTV) using the Jaccard
Conformity Index (JCI) and Geographical Miss Index (GMI). The prognostic value of
JCI and GMI was also assessed. The RT plans were also reviewed against protocol
defined constraints. RESULTS: 60 patients with diagnostic-quality planning scans
were included. The median whole volume JCI for GTV was 0.64 (IQR: 0.43-0.82), and
the median GMI was 0.11 (IQR: 0.05-0.22). For PTVs, the median JCI and GMI were
0.80 (IQR: 0.71-0.88) and 0.04 (IQR: 0.02-0.12) respectively. Tumour was
completely missed in 1 patient, and?50% of the tumour was missed in 3. Patients
with JCI for GTV?0.7 had 7.12 (95% CIs: 1.83-27.67, p=0.005) higher odds of
progressing by 9months in multivariate analysis. Major deviations in RT planning
were noted in 4.5% of cases. CONCLUSIONS: Radiotherapy workshops and real-time
central review of contours are required in RT trials of pancreatic cancer.
PMID- 27497805
TI - Spatial and non-spatial aspects of visual attention: Interactive cognitive
mechanisms and neural underpinnings.
PMID- 27497806
TI - Cost-effectiveness of radial vs. femoral approach in primary percutaneous
coronary intervention in STEMI - Randomized, control trial.
AB - INTRODUCTION AND OBJECTIVES: Primary percutaneous coronary intervention
infarction became the preferred method of treatment for myocardial ST segment
elevation. Improved safety was reported in transradial access (radial) compared
to transfemoral access (femoral). The aim of this study was to compare the cost
between the two access points in ST segment elevation myocardial infarction.
METHODS: This is a subanalysis of the OCEAN RACE trial in which 103 myocardial
infarction patients were randomized to either the radial (n=52) or femoral (n=51)
groups. The clinical safety and efficacy were recorded during the hospital stay.
The procedural metrics were meticulously logged, and costs were evaluated using
the micro-cost method. The indirect costs were estimated using the human capital
approach. RESULTS: Clinical success was numerically higher in the radial group
(90.4 vs. 80.4%, p=0.123). There were no differences in major adverse cardiac
events (9.6% vs. 11.8%, p=0.48) and death (2.0% vs. 6.0%, p=0.31). The average in
hospital cost per patient was 2,740 +/- 1,092 EUR. The cost of therapeutic
success was lower in the radial group at 3,060 EUR vs. 3,374 EUR. The indirect
costs related to absence at work were 138 EUR per patient, which were lower in
the radial group compared to the femoral group. CONCLUSIONS: The total in
hospital costs were similar between the study groups. The indirect costs were
lower in the radial group. Introduction of radial access as the default approach
in all centers may significantly reduce the overall financial burden from a
social perspective.
PMID- 27497807
TI - Cytokine response of human THP-1 macrophages to Trichomonas tenax.
AB - Trichomonas tenax is a protozoan that inhabits the oral cavity of humans, most
often those with poor oral hygiene. Although T. tenax is widely considered a
commensal, recent studies have suggested a pathogenic role for the protozoan in
persons with periodontitis. Here we investigated the capacity of T. tenax to
induce pro-inflammatory cytokine secretion in human macrophages, with the idea
that elicitation of inflammation may be one mechanism by which T. tenax
contributes to oral pathology. Human THP-1 cells differentiated to the macrophage
phenotype (dTHP-1) were incubated with live or sonicated T. tenax at
trophozoite:dTHP-1 ratios of 1:5, 1:10, and 1:20. Culture media removed from the
wells after 4, 8, and 16 h of stimulation were assayed by ELISA for tumor
necrosis factor alpha, interleukin-1 beta, interleukin-8, and the
immunoregulatory cytokine interleukin-10. Live T. tenax trophozoites failed to
induce production of any of the cytokines tested, regardless of trophozoite:dTHP
1 cell ratio or length of co-incubation. T. tenax lysates stimulated interleukin
8 synthesis, but only after 16 h of incubation at the 1:5 trophozoite:dTHP-1 cell
ratio. These results suggest that pro-inflammatory cytokine synthesis by human
macrophages in direct response to T. tenax contributes little to oral pathology.
PMID- 27497808
TI - Plasmin Enzyme-Assisted Vitrectomy in Pediatric Patients with Vitreoretinal
Diseases.
AB - PURPOSE: To evaluate the efficacy and safety of using plasmin-assisted vitrectomy
in pediatric patients with vitreoretinal diseases. METHODS: We prospectively
recruited children aged 16 years or younger who presented with
vitreoretinopathies and underwent plasmin-assisted vitrectomy between 2012 and
2013. The main outcome measure was the induction of posterior vitreous detachment
(PVD) using a suction power of 200 mm Hg or less during surgery. RESULTS: Eleven
eyes of 11 patients (mean age: 3.7 years; average follow-up duration: 14.1
months) were included. Of these 11 patients, there were 3 (27%) cases of stage 5
retinopathy of prematurity, 2 (18%) cases of persistent fetal vasculature, 2
(18%) cases of rhegmatogenous retinal detachment, 2 (18%) cases of idiopathic
epiretinal membrane, 1 (9%) case of traumatic macular pucker, and 1 (9%) case of
traumatic vitreous hemorrhage (9%). PVD was achieved in all cases (100%) during
surgery using low suction after plasmin treatment (mean: 150 +/- 39 mm Hg; range:
100-200). Overall, anatomical success was achieved in 8 eyes (73%). Visual acuity
improved in all 5 (100%) patients for whom vision could be measured at 6 months
after the operation. Cataracts were found in 4 eyes (36%), and a rise in
transient intraocular pressure was observed in 1 eye (9%). CONCLUSIONS: Plasmin
assisted vitrectomy offers an effective and less traumatic intervention for a
variety of pediatric vitreoretinal diseases.
PMID- 27497809
TI - MDA7 combined with targeted attenuated Salmonella vector SL7207/pBud-VP3
inhibited growth of gastric cancer cells.
AB - BACKGROUND/AIM: To investigate the therapeutic effect of MDA7 combined with
apoptin targeted attenuated Salmonella typhimurium vector SL7207/pBud-VP3 on
gastric cancer cells. MATERIALS AND METHODS: MDA7 was inserted into pBud-VP3
using molecular cloning technology to obtain the eukaryotic expression plasmid
pBud-VP3-MDA7 and it was transformed into attenuated Salmonella typhimurium
SL7207 by high voltage electroporation to obtain SL7207/pBud-VP3-MDA7. Mice
bearing a sarcoma of gastric cancer cells were treated with SL7207/pBud-VP3-MDA7
and the growth-suppressing effect was assessed by measurement of tumor volume.
Western blot was used to identify the MDA7 expression products. IL-6, INF-gamma,
TNF-alpha and caspase-3, VEGF in tumor tissue were detected by RT-PCR and
immunohistochemistry. RESULTS: SL7207/pBud-VP3-MDA7 was successfully constructed
and expression of the protein MDA7 was identified in tumor tissue. SL7207/pBud
VP3-MDA7 significantly caused tumor inhibition and regression (p<0.05). The level
of expression of cytokines IL-6, INF-gamma, TNF-alpha in tumor tissue was
significantly higher than in the other groups (p<0.05). The expression of caspase
3 was up-regulated and VEGF was down-regulated (p<0.05). CONCLUSION: This study
shows that SL7207/pBud-VP3-MDA7 has inhibitory effect on the growth of gastric
cancer cells. The mechanism involved is related to the promotion of tumor
apoptosis, immunity regulation and inhibition of tumor blood vessels.
PMID- 27497810
TI - N-methyl-d-aspartate receptor autoimmunity affects cognitive performance in
herpes simplex encephalitis.
AB - OBJECTIVES: To investigate the prevalence and temporal development of N-methyl-d
aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive
performance in patients with herpes simplex encephalitis (HSE). METHODS: This
prospective observational study enrolled a total of 49 HSE patients within a
randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum
samples were drawn in the initial stage of disease, after 2 to 3 weeks and after
3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids
encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests,
including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS),
Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National
Institutes of Health (NIH) stroke scale, was performed during 24 months' follow
up. RESULTS: Anti-NMDAR IgG was detected in 12 of 49 participants. None were
antibody positive in the initial stage of disease. In ten of 12 positive cases,
specific antibodies were detectable only after 3 months. Notably, the development
of NMDAR autoantibodies was associated with significantly impaired recovery of
neurocognitive performance. After 24 months' follow-up, the median increase in
MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative
participants (p=0.018). CONCLUSIONS: Anti-NMDAR autoimmunity is a common
complication to HSE that develops within 3 months after onset of disease. The
association to impaired neurocognitive recovery could have therapeutical
implications, as central nervous system autoimmunity is potentially responsive to
immunotherapy.
PMID- 27497811
TI - Pros and cons of circumcision: an evidence-based overview.
AB - Based on three large randomized controlled trials (RCTs) conducted in Africa, it
can clearly be stated that circumcision lowers the risk of infection with the
human immunodeficiency virus (HIV) and some sexually transmitted infections
(STIs) among males in settings of high HIV and STI endemicity. Similar effects on
STI risk may exist for females, although this may result from an indirect effect
of decreasing risk of infection among male partners. It is unknown whether
circumcision prevents HIV acquisition in men who have sex with men (MSM),
although there might be a protective effect for men who engage mainly in
insertive anal intercourse. When the effects of adult circumcision on sexual
function and satisfaction of men are examined, high-quality evidence strongly
supports lack of harm. Whether circumcision alters sexual satisfaction of female
partners is not known as fewer and smaller studies reported conflicting results.
Circumcision rarely causes serious complications if practiced by trained
practitioners, in a sterile setting, and with a proper follow-up. These
conclusions are limited by the lack of high-quality data from areas outside of
Africa. RCTs have not been conducted to assess the effects of circumcising
infants or MSM. Circumcision has well-proven benefits for people residing in
areas with high prevalence of STIs, including HIV, and is not unethical for those
who choose to be circumcised or have their children circumcised on religious,
social, or cultural grounds. For many others, a definite pro or con
recommendation, based on a risk-benefit ratio, cannot be made.
PMID- 27497812
TI - Closing the evidence gap in infectious disease: point-of-care randomization and
informed consent.
AB - The informed consent document is intended to provide basic rights to patients but
often fails to do so. Patients' autonomy may be diminished by virtue of their
illness; evidence shows that even patients who appear to be ideal candidates for
understanding and granting informed consent rarely are, particularly those with
acute infections. We argue that for low-risk trials whose purpose is to evaluate
nonexperimental therapies or other measures towards which the medical community
is in a state of equipoise, ethics committees should play a more active role in a
more standardized fashion. Patients in the clinic are continually subject to
spontaneous 'pseudo-randomizations' based on local dogma and the anecdotal
experience of their physicians. Stronger ethics oversight would allow point-of
care trials to structure these spontaneous randomizations, using widely available
informatics tools, in combination with opt-out informed consent where deemed
appropriate.
PMID- 27497813
TI - The modulatory effect of nitric oxide in pro- and anti-convulsive effects of
vasopressin in PTZ-induced seizures threshold in mice.
AB - Vasopressin neuropeptides play an important role in the several cognitive,
social, and neuroendocrine functions. Also, several studies report the
involvement of nitrergic system in the vasopressin functions in central nervous
system. This study investigates the effect of Arginine-Vasopressin (AVP) in
pentylenetetrazol (PTZ)-induced seizures threshold and the probable role of
nitric oxide (NO). AVP is administered intraperitoneally (0.01-20MUg/kg, i.p.)
30min before induction of seizures. Administration of AVP (0.1MUg/kg)
significantly lowered the PTZ-induced seizures threshold. But, administration of
AVP (10 and 20MUg/kg) increased the seizures threshold, significantly.
Pretreatment of SR 49059 (V1a receptor antagonist, 2mg/kg, i.p.) just reversed
the pro-convulsant effect of AVP. Meanwhile, SSR 149415 (V1b receptor antagonist,
10mg/kg, i.p.) pretreatment reversed both pro-and anti-convulsant effects of AVP.
The nitric oxide precursor, L-arginine (60mg/kg, i.p.) increased pro-convulsant
effect of AVP, but did not change anticonvulsant activity. The nitric oxide
synthase (NOS) inhibitor L-NAME (10mg/kg, i.p.) reversed both pro- and anti
convulsant effect of AVP. Selective inducible NOS inhibitor, aminoguanidine
(100mg/kg, i.p.) just reversed the anti-convulsant effects of AVP. The results of
the present study showed nitric oxide system may contribute to the biphasic
effects of AVP on PTZ-induced seizures. V1a receptor may modulate only the
proconvulsive effect. While, V1b receptors can mediate both the pro- and anti
convulsive effect of AVP.
PMID- 27497814
TI - How does vagal nerve stimulation (VNS) change EEG brain functional connectivity?
AB - An effect of vagal nerve stimulation (VNS) on cortical synchronization has been
postulated but remains to be verified. In this study we investigated the impact
of VNS on functional connectivity (Fc) using direct intracerebral recordings
(stereotactic EEG, SEEG). Five patients with epilepsy who underwent SEEG
recordings during ongoing VNS therapy were investigated. Interdependencies
between twenty-six selected bipolar SEEG channels were estimated by nonlinear
regression analysis during ON and OF periods of stimulation. In comparison with
OFF periods, the ON periods disclosed higher values for four patients (P1, P3,
P4, P5) and lower values for one patient (P2). From thresholded graphs, we
observed increased connections between several brain regions in P1 and P5 and
decreased connections in P2. Finally, the only decreased Fc occurring during VNS
corresponded to the responder patient, suggesting that therapeutic impact might
be related to this mechanism.
PMID- 27497817
TI - Correction to Lancet Diabetes Endocrinol 2016; 4: 647.
PMID- 27497815
TI - Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history,
and treatment.
AB - : Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic RAS
mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal
dysplasia. Records from 56 individuals were reviewed and demonstrated fractures,
scoliosis, and non-congenital hypophosphatemia that in some cases were resolved.
Phosphate and calcitriol, but not skin lesion removal, were effective at
controlling hypophosphatemia. No skeletal malignancies were found. PURPOSE: CSHS
is a disorder defined by the association of epidermal and/or melanocytic nevi, a
mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date,
somatic RAS mutations have been identified in all patients whose affected tissue
has undergone DNA sequencing. However, the clinical spectrum and treatment are
poorly defined in CSHS. The purpose of this study is to determine the spectrum of
the phenotype, natural history of the disease, and response to treatment of
hypophosphatemia. METHODS: Five CSHS subjects underwent prospective data
collection at clinical research centers. A review of the literature identified 45
reports that included a total of 51 additional patients, in whom the findings
were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and
skeletal disorders, abnormalities in other tissues, and response to treatment of
hypophosphatemia were analyzed. RESULTS: Fractures, limb deformities, and
scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth.
Histology revealed severe osteomalacia but no other abnormalities. Skeletal
dysplasia was reported in all anatomical compartments, though less frequently in
the spine; there was no clear correlation between the location of nevi and the
skeletal lesions. Phosphate and calcitriol supplementation was the most effective
therapy for rickets. Convincing data that nevi removal improved blood phosphate
levels was lacking. An age-dependent improvement in mineral abnormalities was
observed. A spectrum of extra-osseous/extra-cutaneous manifestations that
included both benign and malignant neoplasms was present in many subjects, though
osteosarcoma remains unreported. CONCLUSION: An understanding of the spectrum,
natural history, and efficacy of treatment of hypophosphatemia in CSHS may
improve the care of these patients.
PMID- 27497816
TI - Inhibition of HIF-1alpha enhances anti-tumor effects of dendritic cell-based
vaccination in a mouse model of breast cancer.
AB - Considerable evidence shows that the tumor microenvironment is an active
participant in preventing immunosurveillance and limiting the efficacy of
anticancer therapies. Hypoxia is a prominent characteristic of the solid tumor
microenvironment. The transcription factor hypoxia-inducible factor-1alpha (HIF
1alpha) is an important mediator of hypoxic response of tumor cells that
modulates the expression of specific genes involved in tumor immunosuppression.
Using a 4T1 breast cancer model, we show that in vivo administration of PX-478,
an inhibitor of oxygen-sensitive HIF-1alpha, led to reduced expression of Foxp3
and VEGF transcript and/or protein, molecules that are directly controlled by HIF
1. When combined with dendritic cell (DC)-based vaccination, HIF-1alpha
inhibition resulted in an augmented cytotoxic T lymphocyte effector function,
improved proliferation status of T cells, increased production of inflammatory
cytokine IFN-gamma, as well as reduced regulatory function of T cells in
association with slower tumor growth. Taken together, our findings indicate that
the use of HIF-1alpha inhibition provides an immune adjuvant activity, thereby
improves the efficacy of tumor antigen-based DC vaccine.
PMID- 27497818
TI - Nucleotide variation of sFRP5 gene is not associated with obesity in children and
adolescents.
AB - Because sFRP5 was shown to be an important extracellular modulator of the Wnt
pathway, regulating adipogenesis, we wanted to investigate the role of sFRP5
variants in human, monogenic obesity by performing mutation analysis. We screened
the complete sFRP5 coding region in 622 obese children and adolescents and 503
lean control individuals by high-resolution melting curve analysis and direct
sequencing. We found a total of 15 sequence variants in sFRP5, 10 of which
resulted in a non-synonymous amino acid change. Five of these variants were, to
our knowledge, not previously reported. For one of the variants (c.-3G>A), we
identified a trend towards association between the variant frequency and the
obese phenotype. We argue that, when looking at conservation and location inside
known protein domains, several of the identified variants (D103N, A113V, K212N
and H317L), may affect sFRP5 protein function. In addition, we found c.-3G>A,
residing in the Kozak sequence, with a lower frequency in cases compared to
controls. However, functional studies investigating the effect of sFRP5 variants
on protein function are necessary to determine the true role of sFRP5 genetic
variation in human, monogenic obesity.
PMID- 27497819
TI - Minocycline ameliorates D-galactose-induced memory deficits and loss of
Arc/Arg3.1 expression.
AB - Dysfunction of learning and memory is widely found in many neurological diseases.
Understanding how to preserve the normal function of learning and memory will be
extremely beneficial for the treatment of these diseases. However, the possible
protective effect of minocycline in memory impairment is unknown. We used the
well-established D-galactose rat amnesia model and two behavioral tasks, the
Morris water maze and the step-down task, for memory evaluation. Western blot and
PCR were used to examine the protein and mRNA levels of Arc/Arg3.1. We report
that minocycline supplementation ameliorates both the spatial and fear memory
deficits caused by D-galactose. We also found that Arc/Arg3.1, c-fos, and brain
derived neurotrophic factor levels are decreased in the D-galactose animal model,
and that minocycline reverses the protein and mRNA levels of Arc in the
hippocampus, suggesting the potential role of Arc/Arg3.1 in minocycline's
neuroprotective mechanism. Our study strongly suggests that minocycline can be
used as a novel treatment for memory impairment in neurological diseases.
PMID- 27497820
TI - Gel based in vitro 3D model exploring the osteocytic potentiality of human CD34+
stem cells.
AB - Osteocytic potentiality of human CD34+ stem cells explored in the present study
by generating in vitro agarose gel 3D model to understand the bone ossification
process. The G-CSF and IL-3 mobilized human CD34+ stem cells isolated
apheretically from donor peripheral blood and purity of the cells was assessed by
FACS and immunocytochemical (ICC) studies. The CD34+ stem cells were cultured in
gel based 3D model with osteogenic stimulating medium for 21 days. The transition
stages from undifferentiated to differentiated osteocytes through osteoblasts
were studied with expression markers Differentiated cells at Day 7 showed
positive reactivity with monoclonal anti-Runx2, an early osteoblastic marker.
qPCR expression analysis showed early and mature osteoblastic markers like RUNX2,
Osterix, RANKL, along with osteocyte markers SPARC, Sclerostin. While poor
expression of OSCAR genes was observed apart from conspicuous expression of
alkaline phosphatase. The expression of sclerostin and SPARC suggests that these
differentiated cells are behaving like true osteocytes, sclerostin expression
causes transformation of osteoblast into osteocytes and negligible expression of
OSCAR, RANK, NFATc and cathepsin K genes explains there are no osteoclasts in the
differentiated culture. These cells showed positive reaction with Alizarin red
stain indicating expression of calcium bound bone morphogenic proteins like
osteonectin. All these results clearly confirm the human CD34+ stem cells possess
unique osteogenic differentiation potential and can be used in the early
regeneration of injured bone.
PMID- 27497821
TI - Accidents with biologic material in health services among persons with no
presumed risk.
AB - This study identified persons without presumed risk (PWPR) involved in accidents
with blood and body fluids in 2 health care facilities between 1989 and 2012 in a
state in Central Brazil. There were 181 accidents that occurred with PWPR,
predominantly among women. Accidents with blood and body fluids involved needle
and blood, some performed by untrained personnel. Most prematurely terminated
clinical and laboratory monitoring. Accidents with blood and body fluids occur
under similar circumstances to health care workers.
PMID- 27497822
TI - Joinpoint regression analysis of pertussis crude incidence rates, Illinois, 1990
2014.
AB - Pertussis incidence has increased in recent years; we obtained incidence data
from 1990-2014 from the Illinois Department of Public Health Web site. We
analyzed the crude incidence rates using Joinpoint regression software. Four
joinpoints were observed (2001, 2004, 2007, and 2012). Disease modeling can be
used for disease control and planning by extrapolating the trend in the incidence
data and applying to annual population estimates.
PMID- 27497823
TI - Profiling the fecal carriage of beta-lactamase genes in long-term care facility
residents: A longitudinal study.
AB - BACKGROUND: The fecal carriage of beta-lactamase (BL)-producing bacteria may play
a major role in the spread of these organisms in long-term care facilities
(LTCFs). The aims of this study were (1) to describe the gene profiles of fecal
BL in 3 LCTFs in Taiwan and (2) to analyze the fecal carriage burden of BL genes
between the residents (patient group) and staff (staff group) of LTCFs. METHODS:
Thirty fecal samples were collected during June 2013 and July 2015: 20 were
obtained from 10 residents both during hospitalization (T1) and 1 month after
discharge (T2), and 10 were obtained from 10 staff members. RESULTS: In total,
80%, 70%, and 50% of the samples in the patient group at T1, staff group at T2,
and patient group at T2, respectively, contained >2 BL genes. In the patient
group, the predominant genes belonged to extended-spectrum BL genes (90%-100%)
and AmpC BL genes (90%-100%). Furthermore, carbapenemase genes were approximately
20% during T1 and T2. The relative levels of SHV-type BLs were significantly
higher (P < .05) in the patient group at T2 compared with the staff group.
CONCLUSIONS: In this study, we found a high carriage of fecal BLs among LTCF
residents and staff. The monitoring of fecal BL carriage in LTCFs is needed for
infection control measures and antibiotic choice for health care-associated
infections.
PMID- 27497824
TI - Simethicone residue remains inside gastrointestinal endoscopes despite
reprocessing.
AB - BACKGROUND: During a study designed to assess endoscope reprocessing
effectiveness, a borescope was used to examine lumens and ports. Cloudy, white,
viscous fluid was observed inside fully reprocessed gastroscopes and
colonoscopes. This fluid resembled simethicone, which is commonly administered to
reduce foam and bubbles that impede visualization during gastrointestinal
endoscopy. This article describes methods used to determine whether the observed
fluid contained simethicone. METHODS: Photographs of residual fluid were taken
using a borescope. Sterile cotton-tipped swabs were used to collect samples of
fluid observed in 3 endoscope ports. Samples were evaluated using Fourier
transform infrared spectroscopy (FTIR)-attenuated total reflection analysis.
RESULTS: Residual fluid was observed inside 19 of 20 endoscopes. Fluid
photographed in 8 endoscopes resembled simethicone solutions. FTIR analysis
confirmed the presence of simethicone in 2 endoscopes. CONCLUSIONS: Fluid
containing simethicone remained inside endoscopes despite reprocessing.
Simethicone is an inert, hydrophobic substance that may reduce reprocessing
effectiveness. Simethicone solutions commonly contain sugars and thickeners,
which may contribute to microbial growth and biofilm development. Studies are
needed to assess the prevalence of residual moisture and simethicone in
endoscopes and determine the impact on reprocessing effectiveness. We recommend
minimizing the use of simethicone pending further research into its safety.
PMID- 27497825
TI - How Do Intensity and Duration of Rehabilitation Services Affect Outcomes From
Severe Traumatic Brain Injury? A Natural Experiment Comparing Health Care
Delivery Systems in 2 Developed Nations.
AB - OBJECTIVE: To determine the effects of inpatient and outpatient treatment
intensity on functional and emotional well-being outcomes at 1 year after severe
traumatic brain injury (TBI). DESIGN: Prospective, quasiexperimental study
comparing outcomes in a U.S. TBI treatment center with those in a Denmark (DK)
center providing significantly greater intensity and duration of rehabilitation.
SETTING: Inpatient and outpatient TBI rehabilitation. PARTICIPANTS: Persons with
severe TBI (N=274). INTERVENTIONS: Inpatient rehabilitation interventions were
counted daily by discipline. Outpatient treatments were estimated per discipline
using a structured interview administered to patients, caregivers, or both, at 12
months. MAIN OUTCOME MEASURES: FIM, Glasgow Outcome Scale-Extended, Disability
Rating Scale, Participation Assessment with Recombined Tools-Objective, Perceived
Quality of Life, Medical Outcomes Study 12-Item Short-Form Health Survey, Brief
Symptom Inventory-18-item version. RESULTS: Despite identical inclusion criteria,
patient severity on admission was greater at the DK site. After adjustment for
patient/injury characteristics, there were no site differences in either
functional or emotional outcome at 12 months. Significantly more inpatient plus
outpatient treatment was administered to DK patients than to those in the U.S.
For functional but not emotional treatments, more severely impaired patients
received higher doses. One-year outcomes were predicted by admission severity,
age, employment, and other baseline characteristics. CONCLUSIONS: Contrary to
expectation, DK patients who received significantly more rehabilitation services
during the year after severe TBI did not differ in outcome from their less
intensively treated U.S. counterparts, after adjusting for initial severity. The
negative association of functional treatment dose with extent of early disability
suggests that dose was driven by unmeasured factors reflecting need for services.
Improved measures of injury-related factors driving treatment allocation are
needed to model the independent effects of treatment on outcomes.
PMID- 27497826
TI - Reliability, Validity, and Ability to Identify Fall Status of the Balance
Evaluation Systems Test, Mini-Balance Evaluation Systems Test, and Brief-Balance
Evaluation Systems Test in Older People Living in the Community.
AB - OBJECTIVES: To assess the reliability, validity, and ability to identify fall
status of the Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Brief
BESTest, compared with the Berg Balance Scale (BBS), in older people living in
the community. DESIGN: Cross-sectional. SETTING: Community centers. PARTICIPANTS:
Older adults (N=122; mean age +/- SD, 76+/-9y). INTERVENTIONS: Not applicable.
MAIN OUTCOME MEASURES: Participants reported on falls history in the preceding
year and completed the Activities-Specific Balance Confidence (ABC) Scale. The
BBS, BESTest, and the Five Times Sit-To-Stand Test were administered. Interrater
(2 physiotherapists) and test-retest relative (48-72h) and absolute reliabilities
were explored with the intraclass correlation coefficient (ICC) equation (2,1)
and the Bland and Altman method. Minimal detectable changes at the 95% confidence
level (MDC95) were established. Validity was assessed by correlating the balance
tests with each other and with the ABC Scale (Spearman correlation coefficients
rho). Receiver operating characteristics assessed the ability of each balance
test to differentiate between people with and without a history of falls.
RESULTS: All balance tests presented good to excellent interrater (ICC=.71-.93)
and test-retest (ICC=.50-.82) relative reliability, with no evidence of bias.
MDC95 values were 4.6, 9, 3.8, and 4.1 points for the BBS, BESTest, Mini-BESTest,
and Brief-BESTest, respectively. All tests were significantly correlated with
each other (rho=.83-.96) and with the ABC Scale (rho=.46-.61). Acceptable ability
to identify fall status (areas under the curve, .71-.78) was found for all tests.
Cutoff points were 48.5, 82, 19.5, and 12.5 points for the BBS, BESTest, Mini
BESTest, and Brief-BESTest, respectively. CONCLUSIONS: All balance tests are
reliable, valid, and able to identify fall status in older people living in the
community. Therefore, the choice of which test to use will depend on the level of
balance impairment, purpose, and time availability.
PMID- 27497827
TI - Comparing American Gastroenterological Association Pancreatic Cyst Management
Guidelines with Fukuoka Consensus Guidelines as Predictors of Advanced Neoplasia
in Patients with Suspected Pancreatic Cystic Neoplasms.
AB - BACKGROUND: In 2015, the American Gastroenterological Association (AGA) published
guidelines to provide recommendations for management of suspected pancreatic
cystic neoplasms (PCNs). The aim of this study was to compare efficacy of these
with the Fukuoka consensus guidelines in predicting advanced neoplasia (AN) in
patients with suspected PCNs. STUDY DESIGN: We performed a retrospective study of
239 patients who underwent surgical resection for suspected mucinous PCN at a
tertiary care center from 2000 to 2014. Surgical pathology was the gold standard.
The AGA and Fukuoka criteria were applied, and their performance in predicting
AN, defined as invasive cancer or high-grade dysplasia (HGD), was assessed.
RESULTS: Advanced neoplasia was found in 71 of 239 (29.7%) patients (28 invasive
cancer, 43 HGD). The Fukuoka "high-risk" (FG-HR) and AGA "high-risk" (AGA-HR)
criteria identified patients with AN with sensitivities of 28.2% and 35.2%,
specificities of 95.8% and 94.0%, positive predictive values of 74.1% and 71.4%,
and negative predictive values of 75.9% and 77.5%, respectively. Overall, there
was no significant difference between the guidelines for prediction of AN. There
were 7 and 6 cases with invasive cancer, and 23 and 24 cases with HGD missed by
the FG-HR and AGA-HR guidelines, respectively. CONCLUSIONS: In a retrospective
analysis, the AGA guidelines are not superior to the Fukuoka guidelines in
identifying AN in suspected PCNs. Both sets of guidelines have fair PPV for
detection of AN, which would lead to avoidable resections in patients without AN.
Additionally, the high-risk features of both guidelines do not accurately
identify all patients with AN.
PMID- 27497828
TI - The geographic distribution and complex evolutionary history of the NX-2
trichothecene chemotype from Fusarium graminearum.
AB - Fusarium graminearum and 21 related species comprising the F. sambucinum species
complex lineage 1 (FSAMSC-1) are the most important Fusarium Head Blight
pathogens of cereal crops world-wide. FSAMSC-1 species typically produce type B
trichothecenes. However, some F. graminearum strains were recently found to
produce a novel type A trichothecene (NX-2) resulting from functional variation
in the trichothecene biosynthetic enzyme Tri1. We used a PCR-RFLP assay targeting
the TRI1 gene to identify the NX-2 allele among a global collection of 2515 F.
graminearum. NX-2 isolates were only found in southern Canada and the northern
U.S., where they were observed at low frequency (1.8%), but over a broader
geographic range and set of cereal hosts than previously recognized. Phylogenetic
analyses of TRI1 and adjacent genes produced gene trees that were incongruent
with the history of species divergence within FSAMSC-1, indicating trans-species
evolution of ancestral polymorphism. In addition, placement of NX-2 strains in
the TRI1 gene tree was influenced by the accumulation of nonsynonymous
substitutions associated with the evolution of the NX-2 chemotype, and a
significant (P<0.001) change in selection pressure was observed along the NX-2
branch (omega=1.16) in comparison to other branches (omega=0.17) in the TRI1
phylogeny. Parameter estimates were consistent with positive selection for
specific amino-acid changes during the evolution of NX-2, but direct tests of
positive selection were not significant. Phylogenetic analyses of fourfold
degenerate sites and intron sequences in TRI1 indicated the NX-2 chemotype had a
single evolutionary origin and evolved recently from a type B ancestor. Our
results indicate the NX-2 chemotype may be indigenous, and possibly endemic, to
southern Canada and the northern U.S. In addition, we demonstrate that the
evolution of TRI1 within FSAMSC-1 has been complex, with evidence of trans
species evolution and chemotype-specific shifts in selective constraint.
PMID- 27497829
TI - Trastuzumab Emtansine in HER2+ Recurrent Metastatic Non-Small-Cell Lung Cancer:
Study Protocol.
AB - The treatment outcome has been unsatisfactory for patients with non-small-cell
lung cancer (NSCLC) refractory to standard first-line chemotherapy. Trastuzumab
emtansine (T-DM1), an anti-HER2 antibody conjugated with a vinca alkaloid, has
been approved for clinical use in HER2+ breast cancer in many countries.
Approximately 5% of NSCLC tumors possess HER2 alterations, and T-DM1 has shown
excellent antitumor effects against HER2+ lung cancer cell lines in preclinical
models. Therefore, we hypothesized that T-DM1 could significantly inhibit the
growth of HER2+ lung cancers. We have launched a nonrandomized phase II trial of
T-DM1 monotherapy for patients with HER2+ lung cancers. The major eligibility
criteria are as follows: age >= 20 years, pathologically diagnosed NSCLC with
documented HER2 positivity (immunohistochemistry 3+, both immunohistochemistry 2+
and fluorescence in situ hybridization positive, or exon 20 insertion mutation),
and previous chemotherapy. Thirty patients will receive T-DM1 3.6 mg/kg every 3
weeks. The primary endpoint is the overall response rate. This trial will provide
information on whether T-DM1 monotherapy is effective against HER2+ lung cancer.
PMID- 27497830
TI - Efficient azo dye decolorization in a continuous stirred tank reactor (CSTR) with
built-in bioelectrochemical system.
AB - A continuous stirred tank reactor with built-in bioelectrochemical system (CSTR
BES) was developed for azo dye Alizarin Yellow R (AYR) containing wastewater
treatment. The decolorization efficiency (DE) of the CSTR-BES was 97.04+/-0.06%
for 7h with sludge concentration of 3000mg/L and initial AYR concentration of
100mg/L, which was superior to that of the sole CSTR mode (open circuit: 54.87+/
4.34%) and the sole BES mode (without sludge addition: 91.37+/-0.44%). The
effects of sludge concentration and sodium acetate (NaAc) concentration on azo
dye decolorization were investigated. The highest DE of CSTR-BES for 4h was
87.66+/-2.93% with sludge concentration of 12,000mg/L, NaAc concentration of
2000mg/L and initial AYR concentration of 100mg/L. The results in this study
indicated that CSTR-BES could be a practical strategy for upgrading conventional
anaerobic facilities against refractory wastewater treatment.
PMID- 27497831
TI - Differences between colon and rectal cancer in complications, short-term survival
and recurrences.
AB - PURPOSE: Many apparent differences exist in aetiology, genetics, anatomy and
treatment response between colon cancer (CC) and rectal cancer (RC). This study
examines the differences in patient characteristics, prevalence of complications
and their effect on short-term survival, long-term survival and the rate of
recurrence between RC and CC. METHODS: For all stage II-III CC and RC patients
who underwent resection with curative intent (2006-2008) in five hospitals in the
Netherlands, occurrence of complications, crude survival, relative survival and
recurrence rates were compared. RESULTS: A total of 767 CC and 272 RC patients
underwent resection. Significant differences were found for age, gender,
emergency surgery, T-stage and grade. CC patients experienced fewer complications
compared to RC (p = 0.019), but CC patients had worse short-term mortality rates
(1.5 versus 6.7 % for 30-day mortality, p = 0.001 and 5.2 versus 9.5 % for 90-day
mortality, p = 0.032). The adjusted HR (overall survival) for CC patients with
complications was 1.57 (1.23-2.01; p < 0.001) as compared to patients without
complications; for RC, the HR was 1.79 (1.12-2.87; p = 0.015). Relative survival
analyses showed high excess mortality in the first months after surgery and a
sustained, prolonged negative effect on both CC and RC. Complications were
associated with a higher recurrence rate for both CC and RC; adjusted analyses
showed a trend towards a significant association. CONCLUSION: Large differences
exist in patient characteristics and clinical outcomes between CC and RC. CC
patients have a significantly higher short-term mortality compared to RC patients
due to a more severe effect of complications.
PMID- 27497833
TI - Increased aquaporin 1 and 5 membrane expression in the lens epithelium of
cataract patients.
AB - In this work we have analyzed the expression levels of the main aquaporins (AQPs)
expressed in human lens epithelial cells (HLECs) using 112 samples from patients
treated with cataract surgery and 36 samples from individuals treated with
refractive surgery, with transparent lenses as controls. Aquaporin-1 (AQP1) is
the main AQP, representing 64.1% of total AQPs in HLECs, with aquaporin-5 (AQP5)
representing 35.9% in controls. A similar proportion of each AQP in cataract was
found. Although no differences were found at the mRNA level compared to controls,
a significant 1.65-fold increase (p=0.001) in AQP1protein expression was observed
in HLECs from cataract patients, with the highest differences being found for
nuclear cataracts (2.1-fold increase; p<0.001). A similar trend was found for
AQP5 (1.47-fold increase), although the difference was not significant (p=0.161).
Moreover we have shown increased membrane AQP5 protein expression in HLECs of
patients with cataracts. No association of AQP1 or AQP5 expression levels with
age or sex was observed in either group. Our results suggest regulation of AQP1
and AQP5 at the post-translational level and support previous observations on the
implication of AQP1 and 5 in maintenance of lens transparency in animal models.
Our results likely reflect a compensatory response of the crystalline lens to
delay cataract formation by increasing the water removal rate.
PMID- 27497832
TI - O-GlcNAcylation and neurodegeneration.
AB - O-GlcNAcylation is a dynamic form of protein glycosylation which involves the
addition of beta-d-N-acetylglucosamine (GlcNAc) via an O-linkage to serine or
threonine residues of nuclear, cytoplasmic, mitochondrial and transmembrane
proteins. The two enzymes responsible for O-GlcNAc cycling are O-GlcNAc
transferase (OGT) and O-GlcNAcase (OGA); their expression and activities in brain
are age dependent. More than 1000 O-GlcNAc protein targets have been identified
which play critical roles in many cellular processes. In mammalian brain, O
GlcNAc modification of Tau decreases its phosphorylation and toxicity, suggesting
a neuroprotective role of pharmacological elevation of brain O-GlcNAc for
Alzheimer's disease treatment. Other observations suggest that elevating O-GlcNAc
levels may decrease protein clearance or induce apoptosis. This review highlights
some of the key findings regarding O-GlcNAcylation in models of neurodegenerative
diseases.
PMID- 27497835
TI - The postpartum triathlete.
AB - The postpartum period in a woman's life is filled with numerous changes,
including physical changes, changes in sleep habits, and learning how to best
care for a newborn. A common goal among postpartum women is to either begin or
resume an active lifestyle, which often includes physical activity such as
running, biking and swimming. The postpartum athlete may discover barriers that
prevent her from returning to or beginning an exercise routine. These obstacles
include muscle weakness, fatigue, depression and physical changes that require
exercise modification. The physical therapist is well-suited to properly assess,
treat and manage the care of the postpartum athlete. Postpartum athletes wishing
to begin or resume training for triathlons require special consideration, as the
triathlete must balance training to compete in three different sports. The
purpose of the paper is to identify the unique physical and physiological changes
that occur to the female during the postpartum period. In addition, injuries that
are more commonly seen during the postpartum period will be discussed.
Recommendations for beginning or resuming an exercise program will be reviewed.
Lastly, sport-specific training for the postpartum triathlete, including
challenges presented with each triathlon component, will be discussed.
PMID- 27497834
TI - Alterations in taste perception as a result of hyperbaric oxygen therapy.
AB - The present study evaluates the effect of hyperbaric oxygen therapy on taste
sensitivity, hedonic perception of taste, and food preferences. The studied
groups included 197 people in total (79 in the study group; 118 in the control
group). All patients from the study group were treated with hyperbaric oxygen
therapy due to chronic non-healing wounds. The control group consisted of healthy
people, who did not receive hyperbaric oxygen therapy. The taste intensity,
recognition thresholds, and hedonic perception were examined using gustatory
tests. The aqueous solutions of sucrose for sweet, sodium chloride for salty,
citric acid for sour, quinine hydrochloride for bitter, and monosodium glutamate
for umami taste were used. The participants fulfilled the questionnaire to
examine pleasure derived from eating certain types of dishes. Gustatory tests and
analyses of the pleasure derived from eating in the study group were carried out
before the first exposure to hyperbaric oxygen and then at the end of therapy,
after at least 25 sessions of treatment. In the control group, examination of
perception of taste sensations was conducted only once. The results of comparing
patients with non-healing wounds with healthy people are characterized by reduced
taste sensitivity. After participation in hyperbaric oxygen therapy, the
improvement in perception of taste sensations and changes in hedonic evaluation
have occurred among patients with non-healing wounds. In terms of food
preference, a decreased desire for eating sweet desserts, chocolate, and crisps
was observed in those patients who received hyperbaric oxygen therapy.
PMID- 27497836
TI - Progesterone attenuates impulsive action in a Go/No-Go task for sucrose pellets
in female and male rats.
AB - Impulsivity, or a tendency to act without anticipation of future consequences, is
associated with drug abuse. Impulsivity is typically separated into two main
measures, impulsive action and impulsive choice. Given the association of
impulsivity and drug abuse, treatments that reduce impulsivity have been proposed
as an effective method for countering drug addiction. Progesterone has emerged as
a promising treatment, as it is associated with decreased addiction-related
behaviors and impulsive action. The goal of the present study was to determine
the effects of progesterone (PRO) on impulsive action for food: a Go/No-Go task.
Female and male rats responded for sucrose pellets during a Go component when
lever pressing was reinforced on a variable-interval 30-s schedule. During the
alternate No-Go component, withholding a lever press was reinforced on a
differential reinforcement of other (DRO) behavior 30-s schedule, where a lever
press reset the DRO timer. Impulsive action was operationally defined as the
inability to withhold a response during the No-Go component (i.e. the number of
DRO resets). Once Go/No-Go behavior was stable, responding between rats treated
with PRO (0.5mg/kg) or vehicle was examined. Progesterone significantly decreased
the total number of DRO resets in both males and females, but it did not affect
VI responding for sucrose pellets. This suggests that PRO decreases motor
impulsivity for sucrose pellets without affecting motivation for food. Thus, PRO
may reduce motor impulsivity, a behavior underlying drug addiction.
PMID- 27497837
TI - Eculizumab epitope on complement C5: Progress towards a better understanding of
the mechanism of action.
AB - Eculizumab is an anti-complement C5 monoclonal antibody which has greatly
improved the prognosis and outcomes of nocturnal paroxysmal hemoglobinuria and
atypical hemolytic and uremic syndromes. It is also known to be very species
specific for human C5, despite an important degree of conservation of the
targeted macroglobulin domain, MG7, with that of other primates. However, the
published eculizumab linear epitope does not explain this species specificity.
Sequence analysis, in silico docking and reverse phase protein array were
implemented to fully characterize the eculizumab epitope on human complement C5.
Several residues potentially involved in the species specificity were identified
outside the known epitope by sequence analysis. In silico docking confirmed the
implication of a beta-hairpin located between residues 913 and 922, outside the
known epitope, in the binding of eculizumab to C5. This beta-hairpin spreads from
S913 to I922 and contains a tryptophan residue on position 917 which is unique to
humans. The contribution of both this peptide and the already known one epitope,
which spreads between residues C883 and S891, was validated by reverse phase
protein assay, clearly demonstrating the discontinuous nature of the epitope. Two
residues in particular, Arg885 and Trp917, were defined as major participants in
the interaction of C5 and eculizumab. Their important role was confirmed by the
recent publication of a crystal structure of eculizumab Fab bound to C5. The beta
hairpin not only explains the fine species specificity of eculizumab but is also
an important site at the C5/C5 convertase interface, revealing how eculizumab
acts as a competitor of C5 convertases.
PMID- 27497838
TI - Antenatal group consultations: Facilitating patient-patient education.
AB - OBJECTIVE: This article investigates the perspectives of pregnant women attending
antenatal group consultations to gain their understandings of whether and how
peer learning is facilitated in this setting. METHODS: We conducted semi
structured individual interviews with 16 women who had participated in group
consultations at Aarhus University Hospital, Denmark, and analysed the data using
qualitative content analysis. Our research design also included observations and
patient guest book data. RESULTS: Women who were pregnant for the first time
greatly appreciated the experiential knowledge of multiparous women in the group.
Group consultations provided new learning opportunities, as individuals'
questions prompted learning within the groups, as well as questions and answers.
There was more time for reflection in group consultations than in dyadic
communication. Midwives played a key role in facilitating peer learning. Some
topics were not deemed appropriate for discussion. CONCLUSION: Antenatal group
consultations can support learning, as individuals participate positively both in
their own knowledge acquisition and that of others. We call such peer learning
patient-patient education. PRACTICE IMPLICATIONS: Our study indicates the
strengths of group consultations for learning from the perspective of the group
members. It highlights how learning may be facilitated in group consultations,
and thus has broad practical relevance.
PMID- 27497839
TI - Mollusc models I. The snail Ilyanassa.
AB - Ilyanassa obsoleta has been a model system for experimental embryology for over a
century. Here we highlight new insight into early cell lineage specification in
Ilyanassa. As in all molluscs and other spiralians, stereotyped cleavage patterns
establish a homunculus of regional founder cells. Ongoing studies are beginning
to dissect mechanisms of asymmetric cell division that specify these cells'
fates. This is only part of the story: overlaid on intrinsic cell identities is a
graded 'organizer' signal, and emerging evidence suggests wider roles for short
range intercellular signaling. Modern methods, combined with the intrinsic
experimental advantages of Ilyanassa, offer attractive opportunities for studying
basic developmental cell biology as well as its evolution over a wide range of
phylogenetic scales.
PMID- 27497840
TI - Patient adherence and treatment outcome with exposure and response prevention for
OCD: Which components of adherence matter and who becomes well?
AB - Exposure and response prevention (EX/RP) is an evidence-based treatment for
obsessive-compulsive disorder (OCD), yet not all patients achieve wellness with
EX/RP. The degree to which patients adhere to EX/RP procedures outside of
sessions has been found to predict therapy outcomes, including who achieves post
treatment wellness. We sought to investigate which components of treatment
adherence most relate to outcome and to develop adherence benchmarks to identify
who does and does not become well to provide clinicians with prognostic tools.
Adherence data came from 37 adult patients with DSM-IV OCD who received 17
sessions of EX/RP as part of a randomized controlled trial of augmentation
strategies for incomplete response to serotonin reuptake inhibitors (SRIs).
Therapists rated between-session patient adherence at each exposure session by
quantifying: 1) the quantity of homework exposures attempted; 2) the quality of
attempted exposures; and 3) the degree of success with response prevention. Each
adherence item significantly correlated with post-treatment OCD severity. Success
with response prevention proved particularly strongly linked to therapy outcome.
Time course analysis of this item accurately identified, relatively early in
treatment, who would achieve post-treatment wellness. These data provide an
efficient method for differentiating between those patients who will and will not
achieve wellness after EX/RP augmentation of SRIs. Limitations and clinical
implications of the current findings are discussed.
PMID- 27497841
TI - Low-frequency deep brain stimulation for movement disorders.
AB - INTRODUCTION: Traditionally, deep brain stimulation (DBS) for movement disorders
(MDs) is provided using stimulation frequencies equal to or above 100 Hz.
However, recent evidence suggests that relatively low-frequency stimulation (LFS)
below 100 Hz is an option to treat some patients with MDs. OBJECTIVES: We aimed
to review the clinical and pathophysiological evidence supporting the use of
stimulation frequencies below 100 Hz in different MDs. RESULTS: Stimulation of
the subthalamic nucleus at 60 Hz has provided benefit in gait and other axial
symptoms such as swallowing and speech. Stimulation of the pedunculopontine
nucleus between 20 and 45 Hz can provide benefit in freezing of gait, cognition,
and sleep quality in select patients with Parkinson's disease. Stimulation of the
globus pallidus internus below 100 Hz in patients with dystonia has provided
benefit at the beginning of the therapy, although progressively higher
stimulation frequencies seem to be necessary to maintain the clinical benefit.
Relative LFS can lower energy requirements and reduce battery usage-a useful
feature, particularly in patients treated with high current energy. CONCLUSIONS:
DBS at frequencies below 100 Hz is a therapeutic option in select cases of
Parkinson's disease with freezing of gait and other axial symptoms, and in select
patients with dystonia and other hyperkinetic movements, particularly those
requiring an energy-saving strategy.
PMID- 27497842
TI - Exploration of physical and chemical cues on retinal cell fate.
AB - Identification of the key components in the physical and chemical milieu
directing donor cells into a desired phenotype is a requirement in the
investigation of bioscaffolds for the advancement of cell-based therapies for
retinal neurodegeneration. We explore the effect of electrospun poly-epsilon
caprolactone (PCL) fiber scaffold topography and functionalization and culture
medium, on the behavior of mouse retinal cells. Dissociated mouse retinal post
natal cells were seeded on random or aligned oriented fibers, with or without
laminin coating and cultured with either basic or neurotrophins enriched medium
for 7days. Addition of laminin in combination with neurotrophins clearly promoted
cell- morphology, fate, and neurite extension. Nanotopography per se
significantly affected cell morphology, with mainly bipolar profiles on aligned
fibers and more multipolar profiles on random fibers. Laminin induced a
remarkable 90 degrees switch of neurite orientation. Herewith, we demonstrate
that the chemical cue is stronger than the physical cue for the orientation of
retinal neurites and describe the requirement of both neurotrophins and
extracellular matrix proteins for extended neurite outgrowth and formation of
complex retinal neuronal networks. Therefore, tailor-made PCL fiber mats, which
can be physically and chemically modified, indeed influence cell behavior and
hence motivate further retinal restorative studies using this system.
PMID- 27497843
TI - Multimodal correlative investigation of the interplaying micro-architecture,
chemical composition and mechanical properties of human cortical bone tissue
reveals predominant role of fibrillar organization in determining microelastic
tissue properties.
AB - The mechanical competence of bone is crucially determined by its material
composition and structural design. To investigate the interaction of the complex
hierarchical architecture, the chemical composition and the resulting elastic
properties of healthy femoral bone at the level of single bone lamellae and
entire structural units, we combined polarized Raman spectroscopy (PRS), scanning
acoustic microscopy (SAM) and synchrotron X-ray phase contrast nano tomography
(SR-nanoCT). In line with earlier studies, mutual correlation analysis strongly
suggested that the characteristic elastic modulations of bone lamellae within
single units are the result of the twisting fibrillar orientation, rather than
compositional variations, modulations of the mineral particle maturity, or mass
density deviations. Furthermore, we show that predominant fibril orientations in
entire tissue units can be rapidly assessed from Raman parameter maps. Coexisting
twisted and oscillating fibril patterns were observed in all investigated tissue
domains. Ultimately, our findings demonstrate in particular the potential of
combined PRS and SAM measurements in providing multi-scalar analysis of
correlated fundamental tissue properties. In future studies, the presented
approach can be applied for non-destructive investigation of small pathologic
samples from bone biopsies and a broad range of biological materials and tissues.
STATEMENT OF SIGNIFICANCE: Bone is a complex structured composite material
consisting of collagen fibrils and mineral particles. Various studies have shown
that not only composition, maturation, and packing of its components, but also
their structural arrangement determine the mechanical performance of the tissue.
However, prominent methodologies are usually not able to concurrently describe
these factors on the micron scale and complementary tissue characterization
remains challenging. In this study we combine X-ray nanoCT, polarized Raman
imaging and scanning acoustic microscopy and propose a protocol for fast and easy
assessment of predominant fibril orientations in bone. Based on our site-matched
analysis of cortical bone, we conclude that the elastic modulations of bone
lamellae are mainly determined by the fibril arrangement.
PMID- 27497844
TI - Gelling kinetics and in situ mineralization of alginate hydrogels: A correlative
spatiotemporal characterization toolbox.
AB - Due to their large water content and structural similarities to the extracellular
matrix, hydrogels are an attractive class of material in the tissue engineering
field. Polymers capable of ionotropic gelation are of special interest due to
their ability to form gels at mild conditions. In this study we have developed an
experimental toolbox to measure the gelling kinetics of alginate upon
crosslinking with calcium ions. A reaction-diffusion model for gelation has been
used to describe the diffusion of calcium within the hydrogel and was shown to
match experimental observations well. In particular, a single set of parameters
was able to predict gelation kinetics over a wide range of gelling ion
concentrations. The developed model was used to predict the gelling time for a
number of geometries, including microspheres typically used for cell
encapsulation. We also demonstrate that this toolbox can be used to
spatiotemporally investigate the formation and evolution of mineral within the
hydrogel network via correlative Raman microspectroscopy, confocal laser scanning
microscopy and electron microscopy. STATEMENT OF SIGNIFICANCE: Hydrogels show
great promise in cell-based tissue engineering, however new fabrication and
modification methods are needed to realize the full potential of hydrogel based
materials. The inclusion of an inorganic phase is one such approach and is known
to affect both cell-material interactions and mechanical properties. This article
describes the development of a correlative experimental approach where gel
formation and mineralization has been investigated with spatial and temporal
resolution by applying Raman microspectroscopy, optical and electron microscopy
and a reaction-diffusion modeling scheme. Modeling allows us to predict gelling
kinetics for other geometries and sizes than those investigated experimentally.
Our experimental system enables non-destructive study of composite hydrogel
systems relevant for, but not limited to, applications within bone tissue
engineering.
PMID- 27497845
TI - Biocompatibility and degradation of LAE442-based magnesium alloys after
implantation of up to 3.5years in a rabbit model.
AB - Magnesium as basic implant material has long been the center of orthopedic
research. Latest progress is achieved with a European certification and clinical
use of a magnesium based compression screw. However, long term studies with
implantation duration that exceed one year considerably do not exist. The present
examinations analyzed the degradation progress from nine months to 3.5year after
implantation of cylindrical pins into the medullary cavity of New Zealand White
rabbits. Evaluation included clinical assessment, in vivo MU-computed tomography,
analysis of the implants by three-point-bending and examination of the adjacent
tissue by means of histology and of inner organs by mass- and optical emission
spectrometry using inductively coupled plasma. Clinical acceptance was without
objections in all animals. Immoderate reaction of the surrounding bone could be
found in neither of the applied techniques. While in vivo MU-computed tomography
showed a very slow degradation rate up to 72weeks, three-point-bending revealed a
percentage loss of F(max) of 41.1% for implants after 9months implantation and
88.47% for the implant after 3.5years implantation. Although the total amounts of
RE detected in the inner organs were very low, the organs of rabbits with LAE442
cylinders showed 10-20-fold increased concentrations of the alloying elements
lanthanum, cerium, neodymium and praseodymium compared to animals without any
implanted material. STATEMENT OF SIGNIFICANCE: This is the first animal study
investigating the degradation process of a magnesium alloy in vivo for up to
3.5years. Currently available data from different other in vivo studies cover
only implantation durations up to one year. Therefore, the analysis of these long
time effects in the present study is highly significant and of great interest.
Comprehensive outcome achieved by different techniques was assessed. The
degradation process was slow and homogenous. Maximum applied force (F(max))
reduced by 41.1% for implants after 9months and by 88.47% for the implant after
3.5years implantation. Total amounts of RE detected in the inner organs were very
low; the organs of rabbits with LAE442 cylinders showed 10-20-fold increased
concentrations.
PMID- 27497846
TI - The Use of Anagrelide in Myeloproliferative Neoplasms, with Focus on Essential
Thrombocythemia.
AB - Anagrelide (ANA) is a drug with specific platelet-lowering activity, used
primarily in ET, registered as a second-line drug in essential thrombocythemia
(ET) in Europe and in some countries as first-line therapy, in USA licensed by
FDA for thrombocythemia in myeloproliferative neoplasms (MPN). The platelet
lowering efficacy is similar to that of hydroxycarbamide (HC), around 70 %
complete response and 90 % partial response. Side effects are common, especially
headache and tachycardia, but usually subside or disappear within a few weeks.
Around 20 % of patients stop ANA therapy due to side effects or insufficient
response. Studies of treatment patterns in Europe show that ANA is preferentially
given to younger patients, probably because of the concern for a possible
leukemogenic effect of the common first-line drug, HC. Only two randomized
studies have compared the efficacy of ANA and HC in preventing thrombosis and
haemorrhage, the larger of them showing a slightly better efficacy of HC, the
other showing non-inferiority of ANA to HC. A recent observational 5-year study
of 3600 patients shows a low and basically similar efficacy of ANA and other
cytoreductive therapies in ET. ANA does not appear to inhibit fibrosis
development, and probably due to its anticoagulation properties, the combination
of ASA and ANA produces an increased rate of haemorrhage. Combination of ANA with
HC or interferon (IFN) is feasible and effective in patients with insufficient
platelet response to mono-therapy.
PMID- 27497847
TI - Outcomes of pre-emptive and rescue use of percutaneous left ventricular assist
device in patients with structural heart disease undergoing catheter ablation of
ventricular tachycardia.
AB - PURPOSE: Patient selection and timing of percutaneous left ventricular assist
device (pLVAD) insertion for maximal benefit during ventricular tachycardia (VT)
ablation is not well defined. We aimed to assess the outcomes of pre-emptive and
rescue use of pLVAD during VT ablation in patients with ischemic and non-ischemic
cardiomyopathy. METHODS: Between January 2009 and October 2011, 93 patients
underwent VT ablation. Three groups were compared: (1) Rescue group (n = 12)
patients who required emergent pLVAD insertion due to hemodynamic collapse during
VT ablation, (2) Pre-emptive group (n = 24)-patients who had pre-ablation pLVAD
insertion, and (3) Non-pLVAD group (n = 57)-patients who did not undergo pLVAD
insertion. Procedural outcomes including 30-day mortality were compared. RESULTS:
Thirty-day mortality was higher in the Rescue group compared to the Pre-emptive
group (58 vs. 4 %, p = 0.003) and non-pLVAD (58 vs. 3 %, p = 0.001) group. There
was no significant difference in 30-day mortality or long-term freedom of VT
between the pre-emptive and non-pLVAD groups. CONCLUSIONS: Despite rescue pLVAD
insertion, hemodynamic collapse during VT ablation is associated with a
persistently high 30-day mortality. Further studies are warranted to predict
hemodynamic collapse and to refine the role of pLVAD in this setting.
PMID- 27497848
TI - Functional coupling of TRPV4 channels and BK channels in regulating spontaneous
contractions of the guinea pig urinary bladder.
AB - We investigated the role of TRPV4 channels (TRPV4) in regulating the
contractility of detrusor smooth muscle (DSM) and muscularis mucosae (MM) of the
urinary bladder. Distribution of TRPV4 in DSM and MM of guinea-pig bladders was
examined by fluorescence immunohistochemistry. Changes in the contractility of
DSM and MM bundles were measured using isometric tension recording. Intracellular
Ca(2+) dynamics were visualized by Cal-520 fluorescent Ca(2+) imaging, while
membrane potential changes were recorded using intracellular microelectrode
technique. DSM and MM expressed TRPV4 immunoreactivity. GSK1016790A (GSK, 1 nM),
a TRPV4 agonist, evoked a sustained contraction in both DSM and MM associated
with a cessation of spontaneous phasic contractions in a manner sensitive to HC
067047 (10 MUM), a TRPV4 antagonist. Iberiotoxin (100 nM) and paxilline (1 MUM),
large conductance Ca(2+)-activated K(+) (BK) channel blockers restored the
spontaneous contractions in GSK. The sustained contractions in DSM and MM were
reduced by nifedipine (10 MUM), a blocker of L-type voltage-dependent Ca(2+)
channels (LVDCCs) by about 40 % and by nominally Ca(2+)-free solution by some 90
%. GSK (1 nM) abolished spontaneous Ca(2+) transients, increased basal Ca(2+)
levels and also prevented spontaneous action potential discharge associated with
DSM membrane hyperpolarization. In conclusion, Ca(2+) influx through TRPV4
appears to activate BK channels to suppress spontaneous contractions and thus a
functional coupling of TRPV4 with BK channels may act as a self-limiting
mechanism for bladder contractility during its storage phase. Despite the
membrane hyperpolarization in GSK, Ca(2+) entry mainly through TRPV4 develops the
tonic contraction.
PMID- 27497849
TI - Highway increases concentrations of toxic metals in giant panda habitat.
AB - The Qinling panda subspecies (Ailuropoda melanoleuca qinlingensis) is highly
endangered with fewer than 350 individuals inhabiting the Qinling Mountains.
Previous studies have indicated that giant pandas are exposed to heavy metals,
and a possible source is vehicle emission. The concentrations of Cu, Zn, Mn, Pb,
Cr, Ni, Cd, Hg, and As in soil samples collected from sites along a major highway
bisecting the panda's habitat were analyzed to investigate whether the highway
was an important source of metal contamination. There were 11 sites along a 30-km
stretch of the 108th National Highway, and at each site, soil samples were taken
at four distances from the highway (0, 50, 100, and 300 m) and at three soil
depths (0, 5, 10 cm). Concentrations of all metals except As exceeded background
levels, and concentrations of Cu, Zn, Mn, Pb, and Cd decreased significantly with
increasing distance from the highway. Geo-accumulation index indicated that
topsoil next to the highway was moderately contaminated with Pb and Zn, whereas
topsoil up to 300 m away from the highway was extremely contaminated with Cd. The
potential ecological risk index demonstrated that this area was in a high degree
of ecological hazards, which were also due to serious Cd contamination. And, the
hazard quotient indicated that Cd, Pb, and Mn especially Cd could pose the health
risk to giant pandas. Multivariate analyses demonstrated that the highway was the
main source of Cd, Pb, and Zn and also put some influence on Mn. The study has
confirmed that traffic does contaminate roadside soils and poses a potential
threat to the health of pandas. This should not be ignored when the conservation
and management of pandas is considered.
PMID- 27497850
TI - Polycyclic aromatic hydrocarbons and trace metals in mosque's carpet dust of
Riyadh, Saudi Arabia, and their health risk implications.
AB - The main objectives of this work were to identify and determine the
concentrations of polycyclic aromatic hydrocarbons (PAHs) and trace metals in
carpet dust samples from various mosques of the city of Riyadh and to assess the
health risks associated with the exposure to these pollutants. Therefore, 31
samples of mosque's carpet dust from Riyadh were collected. The results showed
that 14 PAHs were present in the dust samples with concentrations ranged from 90
to 22,146 ng g-1 (mean = 4096 +/- 4277 ng g-1) where low molecular weight
compounds were dominant. The presence of PAHs were in the order of naphthalene >
chrysene and benzo(b)fluoranthene > benzo(a)pyrene > acenaphthene and
benzo(k)fluoranthene > pyrene and the absence of indeno(1,2,3-cd)pyrene and
dibenz(a,h)anthracene. The diagnostic ratio coupled with principle component
analysis (PCA) revealed mix sources of petrogenic from traffic, stack emission,
and pyrogenic inputs from essence and perfumed wood burning. Trace metals were
significant in the dust samples, and their concentrations decrease in the order
of Zn, Mn, Cu, Cr, Pb, Ni, and V where Zn being the highest (94.4 +/- 91.5 MUg g
1) and indium was the lowest (1.9 +/- 9.3 MUg g-1). The trace metals were major
in southern and central parts of Riyadh and followed the order of central Riyadh
> southern Riyadh > western Riyadh > eastern Riyadh > northern Riyadh. Estimated
risk based on the total PAHs was found to be 4.30 * 10-11 for adult and 1.56 * 10
11 for children. Elemental non-cancer risk for adults ranged from 7.9 * 10-4 for
Co to 7.58 * 10-1 for Li and for children ranged from 3.70 * 10-3 for Co to 3.54
for Li. Policy implication and mitigations of PAHs in Riyadh and Saudi Arabia
were highlighted.
PMID- 27497851
TI - The effects of air pollution on human mortality: does gender difference matter in
African countries?
AB - The relationship between environmental factors and human health has long been a
concern among academic researchers. We use two indicators of environmental
pollution, namely particulate matter (PM10) and carbon dioxide (CO2) to examine
the effects of poor air quality on human mortality. This study explores an issue
that has largely been ignored, particularly in the African literature, where the
effect of air pollution on human mortality could be influenced by gender
specification. We analyse a panel data from 35 African countries and our result
suggests that the elevated levels of PM10 and CO2 have a significant effect on
the increasing mortality rates in infants, under-five children and adults.
Although the effect of poor air quality on adults is found to differ between
genders, such difference is not statistically significant. We conclude that the
air pollution effects, on average, are similar between genders in the African
countries.
PMID- 27497852
TI - Geochemical indicators of the origins and evolution of methane in groundwater:
Gippsland Basin, Australia.
AB - Recent expansion of shale and coal seam gas production worldwide has increased
the need for geochemical studies in aquifers near gas deposits, to determine
processes impacting groundwater quality and better understand the origins and
behavior of dissolved hydrocarbons. We determined dissolved methane
concentrations (n = 36) and delta13C and delta2H values (n = 31) in methane and
groundwater from the 46,000-km2 Gippsland Basin in southeast Australia. The basin
contains important water supply aquifers and is a potential target for future
unconventional gas development. Dissolved methane concentrations ranged from
0.0035 to 30 mg/L (median = 8.3 mg/L) and were significantly higher in the deep
Lower Tertiary Aquifer (median = 19 mg/L) than the shallower Upper Tertiary
Aquifer (median = 3.45 mg/L). Groundwater delta13CDIC values ranged from -26.4 to
-0.4 0/00 and were generally higher in groundwater with high methane
concentrations (mean delta13CDIC = -9.5 0/00 for samples with >3 mg/L CH4 vs.
16.2 0/00 in all others), which is consistent with bacterial methanogenesis.
Methane had delta13CCH4 values of -97.5 to -31.8 0/00 and delta2HCH4 values of
391 to -204 0/00 that were also consistent with bacterial methane, excluding one
site with delta13CCH4 values of -31.8 to -37.9 0/00, where methane may have been
thermogenic. Methane from different regions and aquifers had distinctive stable
isotope values, indicating differences in the substrate and/or methanogenesis
mechanism. Methane in the Upper Tertiary Aquifer in Central Gippsland had lower
delta13CCH4 (-83.7 to -97.5 0/00) and delta2HCH4 (-236 to -391 0/00) values than
in the deeper Lower Tertiary Aquifer (delta13CCH4 = -45.8 to -66.2 0/00 and
delta2HCH4 = -204 to -311 0/00). The particularly low delta13CCH4 values in the
former group may indicate methanogenesis at least partly through carbonate
reduction. In deeper groundwater, isotopic values were more consistent with
acetate fermentation. Not all methane at a given depth and location is
interpreted as being necessarily produced in situ. We propose that high dissolved
sulphate concentrations in combination with high methane concentrations can
indicate gas resulting from contamination and/or rapid migration as opposed to in
situ bacterial production or long-term migration. Isotopes of methane and
dissolved inorganic carbon (DIC) serve as further lines of evidence to
distinguish methane sources. The study demonstrates the value of isotopic
characterisation of groundwater including dissolved gases in basins containing
hydrocarbons.
PMID- 27497853
TI - Evaluating the effect of age and area of residence in the metal and metalloid
contents in human hair and urban topsoils.
AB - Monitoring the levels of trace elements in hair can allow estimating the effects
of the geographical location and also can provide a notion of the metal body
burden. However, the use of human hair is controversial due to the different
confounding factors that could affect the presence of trace elements in hair. As
a result, a comprehensive monitoring study was performed in Alcala de Henares,
one of the major cities in the Madrid region, Spain. Trace elements have been
monitored in urban topsoils and in human hair of two well-defined and healthy
groups of population: children (6-9 years) and adolescents (13-16 years). The
city was divided into four areas or zones with different characteristics to
assess the possible effect of area of residence and age in the presence of Al,
As, Be, Cd, Cr, Cu, Hg, Mn, Pb, Sn, Ti, Tl and Zn in soils and hair. There is no
current hypothesis that explains the possible effect of the area of monitoring in
the distribution of Be, Cr, Ni, Sn and Ti found in these urban soils, maybe
because urban soils receive high disturbance, and there are many factors
involved. The presence of most of the trace elements monitored was significantly
higher in the hair of the children population, except for Sn and Zn. This could
be attributed mainly to dietary habits. Other factors influencing metal content
in hair such as environmental factors would have had a minimal effect in the
population groups here studied. Finally, none of the levels of trace elements
studied in hair were significantly correlated with levels measured in the
topsoils of public parks in Alcala de Henares, with the exception of Pb in
adolescent participants.
PMID- 27497854
TI - Photocatalytic ozonation of pesticides in a fixed bed flow through UVA-LED
photoreactor.
AB - In this study, a fixed bed flow through UVA-LED photoreactor was used to compare
the efficiency of ozone, photocatalysis and photocatalysis-ozone degradation, and
mineralization of two pure pesticides, 2,4-dichlorophenoxyacetic acid (2,4-D) and
2-methyl-4-chlorophenoxyacetic acid (MCPA), and a commercial one, Killex(r). For
the degradation of the parent compounds, ozone-based processes were more
effective. While for mineralization, photocatalytic processes were more
effective. Photocatalytic ozonation was the most efficient process for both the
degradation and mineralization of the parent compounds. The degradation rates and
mineralization by photocatalytic ozonation were higher than the summation of the
corresponding rates by ozonation and photocatalysis, indicating a symbiotic
relationship.Overall, the photocatalytic ozonation process with the fixed bed
TiO2 reduces the time needed for the degradation and mineralization of the
pesticides, reduces the costs of powder catalyst separation and overcomes the
reduced efficiency of immobilized catalysts, which makes the process quite
attractive for practical applications.
PMID- 27497855
TI - Fat type in phytosterol products influence their cholesterol-lowering potential:
A systematic review and meta-analysis of RCTs.
AB - The most common form of phytosterol (PS) fortified foods are fat spreads and
dairy products. The predominant fats used are soybean/sunflower (SS) or
rapeseed/canola (RC) oils and animal fat (D) in dairy products. This review aimed
to investigate whether the carrier fat is a determinant of the
hypocholesterolaemic effects of PS fortified foods. Databases were searched using
relevant keywords and published RCTs from 1990 investigating the effects of
dietary PS intervention (>=1.5g per day) on total cholesterol and LDL-C were
included. After methodological quality assessment and data extraction, a total of
32 RCTs (RC, n=15; SS, n=9; D, n=8) were included. As expected, all fat groups
significantly reduced TC and LDL-C (p<0.01). When compared across different
carrier fats, RC as the main carrier fat, reduced LDL-C significantly more than
the SS spreads (p=0.01). Therefore, a combination of monounsaturated fatty acid
rich spread with adequate amounts of omega-3 fatty acids (as evident in RC
spreads) may be the superior carrier fat for the delivery of PS for optimal blood
cholesterol-lowering. The findings of this research provide useful evidence for
optimising the hypocholesterolaemic effects of PS and support further
investigation into the possible mechanisms behind these findings.
PMID- 27497856
TI - Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo
Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA)
Disease-Oriented Group.
AB - Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions
linked by a common histopathologic finding of endothelial damage resulting in
microvascular thromboses and potentially serious complications. The typical
clinical presentation is microangiopathic hemolytic anemia accompanied by
thrombocytopenia with varying degrees of organ ischemia. The differential
diagnoses are generally broad, while the workup is frequently complex and can be
confusing. This statement represents the joint recommendations from a
multidisciplinary team of Mayo Clinic physicians specializing in the management
of TMA. It comprises a series of evidence- and consensus-based clinical pathways
developed to allow a uniform approach to the spectrum of care including when to
suspect TMA, what differential diagnoses to consider, which diagnostic tests to
order, and how to provide initial empiric therapy, as well as some guidance on
subsequent management.
PMID- 27497857
TI - Racial Disparities in Inhospital Outcomes for Hepatocellular Carcinoma in the
United States.
AB - OBJECTIVE: To study racial disparities in therapeutic interventions and
hospitalization outcomes for hepatocellular cancer (HCC) in the United States.
PATIENTS AND METHODS: Using the 2011 Nationwide Inpatient Sample (comprising
hospitalizations between January 1 and December 31, 2011), we identified patients
with HCC-related admissions using previously validated International
Classification of Diseases, Ninth Revision, Clinical Modification codes. Among
these, we also identified those that were procedure-related (associated with
liver transplantation, hepatic resection, radiofrequency ablation, or
transarterial chemoembolization). Multivariate regression was performed to
identify the contribution of race to therapeutic interventions and outcomes.
RESULTS: A total of 22,933 HCC-related hospitalizations were included, of which
10,285 were procedure related (45%). Blacks had a smaller proportion (35%) of
procedure-related HCC hospitalizations than did whites (46%) (odds ratio [OR],
0.65; 95% CI, 0.49-0.86). Specifically, blacks had lower odds of liver
transplantation (OR, 0.43; 95% CI, 0.26-0.71), hepatic resection (OR, 0.57; 95%
CI, 0.33-0.98), and ablation (OR, 0.46; 95% CI, 0.29-0.74) (P=.002) than did
whites. Overall, 10.9% of HCC-related admissions resulted in death in blacks as
compared with 6.4% in whites (OR, 1.58; 95% CI, 1.12-2.24). CONCLUSION: Among
patients admitted for HCC-related hospitalizations, blacks were less likely to
receive liver transplantation, hepatic resection, and ablation than whites and
had higher inhospital mortality. Identifying racial disparities in health care is
a necessary first step to appropriately address and eliminate them.
PMID- 27497858
TI - Measuring physicians' trust: A scoping review with implications for public
policy.
AB - Increasingly, physicians are expected to work in productive, trusting
relationships with other health system stakeholders to improve patient and system
outcomes. A better understanding of physicians' trust is greatly needed. This
study assesses the state of the literature on physicians' trust in patients,
other health care providers, institutions, and data systems or technology, and
identifies key themes, dimensions of trust considered, quantitative measures
used, and opportunities for further development via a scoping review. Peer
reviewed, English-language research articles were identified for inclusion in
this study based on systematic searches of the Ovid/Medline, Pubmed, Proquest,
Scopus, Elsevier, and Web of Science databases. Search terms included "trust"
along with "physician," "doctor," "primary care provider," "family practitioner,"
"family practice," "generalist," "general practitioner," "general practice,"
"internist," "internal medicine," or "health professional," and plausible
variants. Among the relevant articles identified (n = 446), the vast majority
focused on patient trust in physicians (81.2%). Among articles examining
physicians' trust, rigorous investigations of trust are rare, narrowly focused,
and imprecise in their discussion of trust. Robust investigations of the effects
of trust or distrust-as opposed to trust's determinants-and studies using
validated quantitative trust measures are particularly rare. Studies typically
measured trust using the language of confidence, effective communication, or
cooperation, rarely or never capturing other important dimensions of trust, such
as fidelity, the trustee's reputation, social capital, vulnerability, and
acceptance. Research employing new, validated measures of physicians' trust,
especially trust in institutions, may be highly informative to health system
leaders and policymakers seeking to hone and enhance tools for improving the
effectiveness and efficiency of the health care system.
PMID- 27497859
TI - "Whether something cool is good enough": The role of evidence, sales
representatives and nurses' expertise in hospital purchasing decisions.
AB - The emphasis on "value" within healthcare institutions has achieved unprecedented
priority, particularly around the purchase of medical products and equipment.
Health systems and institutions are implementing formal decision-making processes
involving clinicians and supply chain professionals to rationalize purchasing and
promote cost-effective investment. One particular form of this process is the
"Value Analysis" process. Drawing from fieldwork (100 h), interviews (n = 51) and
focus groups (n = 4) conducted from January 2012 to October 2014 at 4 acute care
hospitals in the western United States, I analyze the ways that committee members
constructed and evaluated a case for a product's value. Participants (n = 72)
were a purposive sample including nurses, administrators, supply chain and
industry professionals. Interpretive phenomenology served as the analytic
approach to generating iterative themes. While trying to be evidence-based, Value
Analysis committees lacked data related to a product's price or efficacy and
relied heavily on local knowledge and expertise. Sales representatives were an
integral part of the process, creating interest in the product and providing
product information. As vehicles for cost-savings and quality improvement,
purchasing committees need unique support that emphasizes local contexts and
expertise, while maintaining rigor and minimizing bias. Drawing from
participants' experiences, and principles of health technology assessment and
economic evaluation, a guiding framework is proposed to support this decision
making.
PMID- 27497860
TI - Truth and lies: Disclosure and the power of diagnosis.
AB - The moment at which a diagnosis is delivered to a patient, particularly when it
is serious, is an important social moment. It not only dictates the clinical
pathway, it also rewrites the patient narrative, shifts their identity, predicts
potential outcomes, and foregrounds mortality. It may provide a sense of relief,
or one of despair. Over time, and across cultures, there have been many different
approaches used to palliate the potential impact of the diagnostic utterance on
the patient. France, as one example, provides an interesting case study. Until
the turn of the century, cancer diagnoses were often concealed from patients.
However, recent legislation now requires full diagnostic disclosure according to
prescribed protocols. Using Zerubavel's social patterning methodology, and
transcultural historical methods, I seek to understand beliefs about the
potential impact of the diagnostic moment by identifying common features across
cultural and historical social contexts. I examine writings of French
oncologists, and physicians in related fields, from the pre- and post-legislation
era who discuss if and how a cancer diagnosis should be disclosed to the patient.
While the approach to diagnostic disclosure has changed significantly, medical
representations of diagnostic power have not. The diagnostic utterance is still
cast by medical professionals as a terrifying and life-disrupting moment.
PMID- 27497861
TI - Syrian crisis: aid delivery becoming increasingly difficult.
PMID- 27497862
TI - Human neural stem cells in patients with chronic ischaemic stroke (PISCES): a
phase 1, first-in-man study.
AB - BACKGROUND: CTX0E03 is an immortalised human neural stem-cell line from which a
drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent
improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after
middle cerebral artery occlusion stroke prompted investigation of the safety and
tolerability of this treatment in stroke patients. METHODS: We did an open-label,
single-site, dose-escalation study. Men aged 60 years or older with stable
disability (National Institutes of Health Stroke Scale [NIHSS] score >=6 and
modified Rankin Scale score 2-4) 6-60 months after ischaemic stroke were
implanted with single doses of 2 million, 5 million, 10 million, or 20 million
cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging
data were collected over 2 years. The primary endpoint was safety (adverse events
and neurological change). This trial is registered with ClinicalTrials.gov,
number NCT01151124. FINDINGS: 13 men were recruited between September, 2010, and
January, 2013, of whom 11 (mean age 69 years, range 60-82) received CTX-DP.
Median NIHSS score before implantation was 7 (IQR 6-8) and the mean time from
stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven
had right-hemisphere infarcts. No immunological or cell-related adverse events
were seen. Other adverse events were related to the procedure or comorbidities.
Hyperintensity around the injection tracts on T2-weighted fluid-attenuation
inversion recovery MRI was seen in five patients. At 2 years, improvement in
NIHSS score ranged from 0 to 5 (median 2) points. INTERPRETATION: Single
intracerebral doses of CTX-DP up to 20 million cells induced no adverse events
and were associated with improved neurological function. Our observations support
further investigation of CTX-DP in stroke patients. FUNDING: ReNeuron Limited.
PMID- 27497863
TI - Age of PISCES: stem-cell clinical trials in stroke.
PMID- 27497864
TI - Photoluminescence properties and thermal stability of blue-emitting Ba5
xCl(PO4)3:xEu2+ (0.004<=x<=0.016) phosphors.
AB - A series of blue-emitting Ba5-xCl(PO4)3:xEu2+ (0.004<=x<=0.016) phosphors were
synthesized by conventional high-temperature solid state reaction. The structure
and photoluminescence (PL) properties of the phosphors were investigated. The as
prepared phosphors exhibit broad excitation band ranging from 250 to 420nm, and
strong asymmetric blue emission band peaking at 436nm. The optimum concentration
of Eu2+ in the Ba5Cl(PO4)3:Eu2+ phosphor is x=0.01, and the concentration
quenching mechanism is verified to be the combined actions of dipole-dipole
interaction and radiation re-absorption mechanism. The thermal stability of
Ba5Cl(PO4)3:Eu2+ was evaluated by temperature-dependent PL spectra. Compared with
that of commercial BaMgAl10O17:Eu2+ (BAM) phosphor, the Ba5-xCl(PO4)3:xEu2+
phosphors exhibit similarly excellent thermal quenching property. In addition,
the CIE chromaticity coordinates of Ba5-xCl(PO4)3:xEu2+ (0.004<=x<=0.016) were
calculated to evaluate the color quality. All the results indicate that
Ba5Cl(PO4)3:Eu2+ is a promising candidate phosphor for near-ultraviolet (n-UV)
pumped LED.
PMID- 27497865
TI - A theoretical study on monoatomic BN nanochains and nanorings.
AB - Boron nitride (BN) nanochains were successfully synthesized recently. In this
work, we investigate the electronic, energetic, and structural properties of BN
nanochains and nanorings by means of density functional theory calculations. Our
calculations support the experimental findings and offer additional physical
insights into these new nanostructured materials. We show that BN nanochains are
biracial compounds that tend to be closed and form a ring. They have single and
double bonds alternately throughout the chain. The boron atoms are not saturated
and are strong Lewis acids. Increase in the length of the chain tends to result
in the conversion from a semiconductor to a semimetal material. The ring
structures are stabler than the corresponding chains, and unlike the chains these
structures are predicted to be insulators. The binding energy of the chains and
rings increases with an increase in their size. Rings with odd or even numbers of
BN units show different electronic properties.
PMID- 27497866
TI - The association between oral health literacy and missed dental appointments.
AB - BACKGROUND: In this study, the author identified associations among demographic
characteristics, dental risk factors, health-seeking behaviors, oral health
literacy level, and failure to keep dental appointments. METHODS: The author
conducted an unmatched 1:2 case-control study at a university-based dental clinic
from February through April 2015. The author used the Comprehensive Measure of
Oral Health Knowledge questionnaire to record the oral health literacy of the
respondents. The author obtained additional information about the various
covariates using a questionnaire and checking the patients' electronic medical
records. The author used a multivariate logistic regression analysis to test the
associations between missed appointments and other risk factors in addition to
oral health literacy. RESULTS: Data from 150 (50 case patients and 100 control
patients) respondents were included in the analysis. The case and control
patients were comparable in terms of sociodemographic characteristics and dental
risk factors. The Comprehensive Measure of Oral Health Knowledge score was used
to categorize the sample into low (<= 18) and high (> 18) oral health literacy
groups. Low oral health literacy was associated with a 2-fold increase in the
risk of having missed appointments (adjusted odds ratio, 2.38; 95% confidence
interval, 1.05-5.40). Age was also independently associated with missed
appointments (adjusted odds ratio, 1.03; 95% confidence interval, 1.01-1.06).
CONCLUSIONS: After adjusting for the various demographic and dental risk factors,
poor oral health literacy was found to be independently associated with missed
dental appointments. Insights into the role of oral health literacy and clinic
attendance could play an important role in addressing the problem of missed
dental appointments. PRACTICAL IMPLICATIONS: Considering the effects of missed
appointments on treatment outcomes, predictors of patient compliance behaviors
may be useful in circumventing cancellations and no shows.
PMID- 27497867
TI - The "de-aging" of the dentist workforce.
PMID- 27497868
TI - Multiplex method for initial complex testing of antibodies to blood transmitted
diseases agents.
AB - Initial screening of donors and population at high risk of infection with blood
transmitted diseases involves a number of analyses using monospesific diagnostic
systems, and therefore is expensive labor- and time-consuming process. The goal
of this work is to construct a multiplex test enabling to carry out rapid initial
complex testing at a low price. The paper describes a kit making it possible to
detect simultaneously antibodies to six agents of the most significant blood
transmitted diseases: HIV virus, hepatitis B and C viruses, cytomegalovirus, T.
pallidum and T. gondii in blood products. The kit comprises multiplex dot
immunoassay based on plane protein arrays (immune chips) using colloidal gold
conjugates and silver development. It provides an opportunity to carry out
complex analysis within 70min at room temperature, and there is no need of well
qualified personnel. We compared laboratory findings of the kit with monospecific
kits for ELISA produced by two Russian commercial companies. Dot-assay results
correlate well with data obtained using commercial kits for ELISA. Furthermore,
multiplex analysis is quicker and cheaper in comparison with ELISA and can be
carried out in non-laboratory conditions. The kit for multiplex dot-immunoassay
of antibodies to blood transmitted agents can significantly simplify initial
complex testing.
PMID- 27497869
TI - Cytotoxic constituents of Alocasia macrorrhiza.
AB - An indole alkaloid, 2-(5-hydroxy-1H-indol-3-yl)-2-oxo-acetic acid (1) isolated
for the first time from nature, in addition to the nine known compounds 5-hydroxy
1H-indole-3-carboxylic acid methyl ester (2), alocasin B (3), hyrtiosin B (4),
alpha-monopalmitin (5), 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2(R)
hydroctadecanoyl) amido]-4,8-octadecadiene-1,3-diol (6), 3-epi-betulinic acid
(7), 3-epi-ursolic acid (8), beta-sitosterol (9) and beta-sitosterol 3-O-beta-D
glucoside (10) were isolated from the rhizomes of Alocasia macrorrhiza (Araceae).
Their structures were elucidated by 1D and 2D NMR spectroscopic data. Of these
compounds, 6 exhibited the strongest cytotoxicity against the four tested human
cancer cell lines (IC50 of about 10 uM against Hep-2 larynx cancer cells).
PMID- 27497870
TI - Semiparametric Regression Estimation for Recurrent Event Data with Errors in
Covariates under Informative Censoring.
AB - Recurrent event data arise frequently in many longitudinal follow-up studies.
Hence, evaluating covariate effects on the rates of occurrence of such events is
commonly of interest. Examples include repeated hospitalizations, recurrent
infections of HIV, and tumor recurrences. In this article, we consider
semiparametric regression methods for the occurrence rate function of recurrent
events when the covariates may be measured with errors. In contrast to the
existing works, in our case the conventional assumption of independent censoring
is violated since the recurrent event process is interrupted by some correlated
events, which is called informative drop-out. Further, some covariates may be
measured with errors. To accommodate for both informative censoring and
measurement error, the occurrence of recurrent events is modelled through an
unspecified frailty distribution and accompanied with a classical measurement
error model. We propose two corrected approaches based on different ideas, and we
show that they are numerically identical when estimating the regression
parameters. The asymptotic properties of the proposed estimators are established,
and the finite sample performance is examined via simulations. The proposed
methods are applied to the Nutritional Prevention of Cancer trial for assessing
the effect of the plasma selenium treatment on the recurrence of squamous cell
carcinoma.
PMID- 27497871
TI - Cloning and comparative analysis the proximal promoter activities of arginase and
agmatinase genes in Apostichopus japonicus.
AB - Our previous work demonstrated that Apostichopus japonicus arginase and
agmatinase from l-arginine metabolism synergistically compete with NOS under
pathogens challenge. Here we conducted a study to further investigate the
mechanism in the regulation of arginase and agmatinase genes in l-arginine
metabolism using EPC cell system. Luciferase analysis and progressive 5' deletion
analysis suggested that Ajagmatinase promoter was a very robust promoter for its
transcription, and the core region of Ajarginase promoter was located within -277
bp to -157 bp. Besides, their promoter activities were significantly activated by
LPS and l-arginine challenge both in a time- and dose-dependent manners in EPC
cells. When different truncated reporter vector and expression vector co
transfection experiment revealed transcription factor NF-kappaB/Rel and STAT5
could significantly inhibited Ajarginase promoter activity, but not Ajagmatinase.
Our findings were provided novel insights into the transcriptional regulation of
Ajarginase and Ajagmatinase, and selectively change their expressions might
prevent pathogens infection.
PMID- 27497872
TI - Antibody repertoire development in fetal and neonatal piglets. XXIV. Hypothesis:
The ileal Peyer patches (IPP) are the major source of primary, undiversified IgA
antibodies in newborn piglets.
AB - The ileal Peyers patches (IPP) of newborn germfree (GF) piglets were isolated
into blind loops and the piglets colonized with a defined probiotic microflora.
After 5 weeks, IgA levels in the intestinal lavage (IL) of loop piglets remained
at GF levels and IgM comprised ~70% while in controls, IgA levels were elevated 5
fold and comprised ~70% of total Igs. Loop piglets also had reduced serum IgA
levels suggesting the source of serum IgA had been interrupted. The isotype
profile for loop contents was intermediate between that in the IL of GF and
probiotic controls. Surprisingly, colonization alone did not result in repertoire
diversification in the IPP. Rather, colonization promoted pronounced
proliferation of fully switched IgA(+)IgM(-) B cells in the IPP that supply
early, non-diversified "natural" SIgA antibodies to the gut lumen and a primary
IgA response in serum.
PMID- 27497873
TI - Mycobacterium tuberculosis strains exhibit differential and strain-specific
molecular signatures in pulmonary epithelial cells.
AB - Although pulmonary epithelial cells are integral to innate and adaptive immune
responses during Mycobacterium tuberculosis infection, global transcriptomic
changes in these cells remain largely unknown. Changes in gene expression induced
in pulmonary epithelial cells infected with M. tuberculosis F15/LAM4/KZN, F11,
F28, Beijing and Unique genotypes were investigated by RNA sequencing (RNA-Seq).
The Illumina HiSeq 2000 platform generated 50 bp reads that were mapped to the
human genome (Hg19) using Tophat (2.0.10). Differential gene expression induced
by the different strains in infected relative to the uninfected cells was
quantified and compared using Cufflinks (2.1.0) and MeV (4.0.9), respectively.
Gene expression varied among the strains with the total number of genes as
follows: F15/LAM4/KZN (1187), Beijing (1252), F11 (1639), F28 (870), Unique (886)
and H37Rv (1179). A subset of 292 genes was commonly induced by all strains,
where 52 genes were down-regulated while 240 genes were up-regulated.
Differentially expressed genes were compared among the strains and the number of
induced strain-specific gene signatures were as follows: F15/LAM4/KZN (138),
Beijing (52), F11 (255), F28 (55), Unique (186) and H37Rv (125). Strain-specific
molecular gene signatures associated with functional pathways were observed only
for the Unique and H37Rv strains while certain biological functions may be
associated with other strain signatures. This study demonstrated that strains of
M. tuberculosis induce differential gene expression and strain-specific molecular
signatures in pulmonary epithelial cells. Specific signatures induced by clinical
strains of M. tuberculosis can be further explored for novel host-associated
biomarkers and adjunctive immunotherapies.
PMID- 27497874
TI - Shrimp with knockdown of LvSOCS2, a negative feedback loop regulator of JAK/STAT
pathway in Litopenaeus vannamei, exhibit enhanced resistance against WSSV.
AB - JAK/STAT pathway is one of cytokine signaling pathways and mediates diversity
immune responses to protect host from viral infection. In this study, LvSOCS2, a
member of suppressor of cytokine signaling (SOCS) families, has been cloned and
identified from Litopenaeus vannamei. The full length of LvSOCS2 is 1601 bp,
including an 1194 bp open reading frame (ORF) coding for a putative protein of
397 amino acids with a calculated molecular weight of ~42.3 kDa. LvSOCS2
expression was most abundant in gills and could respond to the challenge of LPS,
Vibrio parahaemolyticus, Staphhylococcus aureus, Poly (I: C) and white spot
syndrome virus (WSSV). There are several STAT binding motifs presented in the
proximal promoter region of LvSOCS2 and its expression was induced by LvJAK or
LvSTAT protein in a dose dependent manner, suggesting LvSOCS2 could be the
transcriptional target gene of JAK/STAT pathway. Moreover, the transcription of
DmVir-1, a read out of the activation of JAK/STAT pathway in Drosophila, was
promoted by LvJAK but inhibited by LvSOCS2, indicating that LvSOCS2 could be a
negative regulator in this pathway and thus can form a negative feedback loop.
Our previous study indicated that shrimp JAK/STAT pathway played a positive role
against WSSV. In this study, RNAi-mediated knockdown of LvSOCS2 shrimps showed
lower susceptibility to WSSV infection and caused lessened virus loads, which
further demonstrated that the JAK/STAT pathway could function as an anti-viral
immunity in shrimp.
PMID- 27497875
TI - Health and epidemiological approaches of Trypanosoma evansi and equine infectious
anemia virus in naturally infected horses at southern Pantanal.
AB - Equine infectious anemia virus (EIAV) and Trypanossoma evansi are endemic in
Brazilian Pantanal Biome, an important area for livestock production. In this
sense, we evaluated the epidemiological single and co-infection effects of T.
evansi and EIAV in naturally infected horses in the southern Pantanal wetland by
serological tests and hematological assays. Both higher seroprevalence and heath
poor condition of the sampled animals were associated with differences in horse
management between farms. We found that the negative animals for both infectious
agents (NN) represented the major group in F1 (37%), and the smallest group in F2
(19%). Furthermore, we recorded higher EIAV seroprevalence (56%) in F2, compared
to F1 (38%). We observed that T. evansi infection was mostly related to young
horses, as seen by their higher seroprevalence, ranging from 70.7% in the
beginning of the rainy season to 81% in the end of flood period, in comparison
with the values of 42% and 68%, respectively, in working animals. on the other
hand, working animals showed a higher seroprevalence for EIAV (48%) in both
seasons than young horses. We observed that the management of working horses
could be a risk factor of EIAV infection. On the other hand, as T. evansi is
maintained in the study region by many species of wild mammals, the mechanical
transmission through blood-sucking vectors ensures the infection to horses since
early. Our results showed that single or co-infection by EIAV and T. evansi
caused different degree of anemia in the infected animals. Moreover, the health
of horses in Brazilian Pantanal is also influenced by differences in horse
management and environmental circumstances.
PMID- 27497876
TI - Comment on "Management of postprandial glucose: Recommended targets and treatment
with biphasic insulin".
PMID- 27497877
TI - Oral health-related quality of life improves in employees with disabilities
following a workplace dental intervention.
AB - This pilot study evaluated a dental intervention for employees with disabilities
by measuring changes in self-rated oral health, dental behaviours and oral health
related quality of life (OHRQol). Consenting employees with disabilities
(>=18years) at two worksites in South Australia underwent dental examinations at
baseline, three and six months. Referrals were arranged as needed to public
dental clinics. At one and two months a dental hygienist provided group oral
health education to the employees. Employees' demographics, self-rated oral
health, dental behaviours and OHRQol were collected via face-to-face interviews.
Of the 39 referred employees, 28 (72%) of them completed the recommended
treatment. Self-rated oral health improved and there were significant reductions
in the prevalence of oral health impact on quality of life (percentage of
employees reporting 1+ items fairly/very often) from 27% to 11% (McNemar's test,
p<0.05); the extent of impact (mean number of items reported fairly/very often)
from 1.3 to 0.6 and the severity of impact (mean of summed OHIP item scores) from
3.6 to 1.8 (paired t-tests, p<0.01). As this pilot study indicates that enabling
urgent referral for treatment and regular oral health education can improve
OHRQol and self-rated oral health among employees with disabilities, a larger
study with a control group should be undertaken.
PMID- 27497878
TI - A Smart pH-responsive Nano-Carrier as a Drug Delivery System: A hybrid system
comprised of mesoporous nanosilica MCM-41 (as a nano-container) & a pH-sensitive
polymer (as smart reversible gatekeepers): Preparation, characterization and in
vitro release studies of an anti-cancer drug.
AB - A smart pH-responsive drug nano-carrier for controlled release of anti-cancer
therapeutics was developed through a facile route. The nano-carrier consisted of
two main parts: first, the nano-container part (that mesoporous silica
nanoparticles (MCM-41) were selected for this aim); and second, pH-sensitive
gatekeepers (that a pH-sensitive polymer, Poly4-vinylpyridine, played this role).
In the first step, MCM-41 was synthesized via template assisted sol-gel process.
In the second step, polymerizable functional groups were attached onto pore
entrances rather than inside walls. In the third step, polymeric gatekeepers were
introduced onto pore entrances via precipitation polymerization of functionalized
MCM-41 with monomers. Different methods and analysis, such as Fourier Transform
Infrared Spectroscopy (FT-IR), X-ray Powder Diffraction (XRD), Thermo-Gravimetric
Analysis (TGA), Energy-Dispersive X-ray Spectroscopy (EDX), Zeta Potentials,
Dynamic Light Scattering (DLS), Field Emission Scanning Electron Microscope (FE
SEM) and Transmission Electron Microscopy (TEM) were employed to approve the
successful attachment of gatekeepers. Furthermore, the release studies of
methotroxate (MTX), an anti-cancer drug, were performed in different media (pH4,
5.8 and 7.4) at 37+/-1 degrees C. The release profiles and curves show that the
release rates are completely pH-dependent and it proceeds with a decrease in pH.
It is concluded that in the higher pH the gatekeepers are in their close state,
but they switch to the open state as a consequence of repulsive forces between
positively charged polymer chains appear in acidic media. The results suggest
that this smart nano-carrier can be considered as an appropriate candidate to
deliver therapeutics to cancerous tissues.
PMID- 27497879
TI - In vivo tissue sampling using solid-phase microextraction for non-lethal exposome
wide association study of CYP1A1 induction in Catostomus commersonii.
AB - Fish are widely used for monitoring aquatic ecosystem health and water
contamination by organic toxicants from natural and anthropogenic sources.
However, most of these studies only focused on the measurement of specific
toxicants and did not examine the impact of chemical mixtures. In this study, we
examined whether the tissue exposome captured in vivo with solid-phase
microextraction (SPME) without lethal sampling and analyzed by liquid
chromatography-high resolution mass spectrometry can detect differences between
Catostomus commersonii exhibiting a significant induction of CYP1A1, through
case/control comparisons, controlling for false discovery rates. We observed the
presence of environmental toxicants in induced case fish known as potential
inducers of CYP1A1. We also found significant changes in the levels of anti
oxidants, short-lived oxysterols and other lipids associated with CYP1A1
induction, possibly due to oxidative stress, lipid peroxidation and free fatty
acids mobilization to maintain homeostatic state. In vivo SPME opens the way to
perform repeated sampling on the same animal over the time and explore the
individual internal exposome trajectory for better characterization of the links
between toxicant load and health effects, at the individual scale.
PMID- 27497881
TI - Nitric oxide and Kir6.1 potassium channel mediate isoquercitrin-induced
endothelium-dependent and independent vasodilation in the mesenteric arterial bed
of rats.
AB - The vascular effect of flavonoid isoquercitrin was investigated in the perfused
mesenteric vascular bed of rats. In preparations with functional endothelium
isoquercitrin (100, 300 and 1000nmol) dose-dependently reduced the perfusion
pressure by 13+/-2.2, 33+/-3.9, and 58+/-3.7mm Hg, respectively. Endothelium
removal or inhibition of the nitric oxide synthase enzymes by l-NAME did not
change the effects of 100 and 300 nmol isoquercitrin, but reduced by 30-40% the
vasodilation induced by 1000 nmol isoquercitrin. Perfusion with nutritive
solution containing 40mM KCl abolished the vasodilatory effect of all
isoquercitrin doses. Treatment with glibenclamide, a Kir6.1 (ATP-sensitive)
potassium channel blocker, inhibited vasodilation induced by 100 and 300 nmol
isoquercitrin, but only partially reduced the effect of 1000 nmol isoquercitrin.
The non-selective KCa (calcium-activated) potassium channel blocker
tetraethylammonium, but not the selective KCa1.1 channel blocker iberiotoxin,
reduced by around 60% vasodilation induced by all isoquercitrin doses. In
addition, association of tetraethylammonium and glibenclamide, or l-NAME and
glibenclamide, fully inhibited isoquercitrin-induced vasodilation. Our study
shows that isoquercitrin induces vasodilation in resistance arteries, an effect
mediated by K(+) channel opening and endothelial nitric oxide production.
PMID- 27497880
TI - Balloon assisted retraction of a migrated CoreValve Evolut R bioprosthesis during
cardiac arrest.
AB - We describe a case of balloon assisted retraction of a migrated CoreValve Evolut
R bioprosthesis during trans-femoral TAVI.
PMID- 27497882
TI - Neuroprotective effects of Kaempferide-7-O-(4"-O-acetylrhamnosyl)-3-O-rutinoside
on cerebral ischemia-reperfusion injury in rats.
AB - In the present study, we aim to evaluate the potential neuroprotective effect and
the underlying mechanism of Kaempferide-7-O-(4"-O-acetylrhamnosyl)-3-O-rutinoside
(A-F-B) against cerebral I/R injury. Adult male rats were pretreated with A-F-B
by intragastric administration once a day for 3 days. One hour after the third
day administration, animals were subjected to 2h of transient middle cerebral
artery occlusion (MCAO) followed by 24h of reperfusion. Neurological deficit,
infarct volume, histopathological changes, oxidative stress-related biochemical
parameters, neuronal apoptosis, apoptosis-related proteins and the expression of
pro-inflammator cytokines genes were measured. A-F-B significantly decreased
neurological and histological deficits, reduced the infarct volume, and decreased
neuroapoptosis. Meanwhile, A-F-B inhibited the expression of Bax, cleaved caspase
3, cleaved caspase-9, and promoted Bcl-2 expression. In addition, the expression
of pro-inflammator cytokines, including phospho-NF-kBp65, interleukin-1beta,
interleukin-6, tumor necrosis factor-alpha, intercellular adhesion molecule-1,
cyclooxygenase-2 and inducible nitric oxide synthase, were also suppressed by A-F
B pretreatment. Furthermore, pretreatment with A-F-B could significantly increase
the activities of superoxide dismutase, glutathione peroxidase, but decrease the
content of malondiadehyde in blood serum. These results suggest that A-F-B has
the neuroprotective effect in ischemic stroke by suppressing neuroinflammation,
reactive oxygen species and neuroapoptosis.
PMID- 27497883
TI - New EGFR inhibitor, 453, prevents renal fibrosis in angiotensin II-stimulated
mice.
AB - Chronic activation of renin-angiotensin system (RAS) greatly contributes to renal
fibrosis through the over expression of angiotensin (Ang) II, ultimately leading
to chronic kidney disease (CKD). As the main peptide in the RAS, Ang II is a key
regulator of nephrotic inflammation, fibrogenic destruction and hypertensive
nephropathy. Controlled by growth factors such as TGF-beta, Ang II is thought to
be affected by other such growth factors including epidermal growth factor (EGF)
due to its ability to stimulate growth, regulate angiogenesis, and desensitize
cells from apoptotic stimuli. Here we show that epidermal growth factor receptor
(EGFR) plays a key role in Ang II induced renal fibrosis and its inhibition for
the use as an effective treatment of CKD. 453, an AG1478 analog, was used to
block the EGF-EGFR interaction in vivo in 4-week old mice treated with Ang II and
453. Along with the inhibition of EGFR and its downstream signaling pathways (AKT
and ERK), 453 also prevented the activation of fibrotic (collagen, CFGF, TGF
beta), inflammatory (COX2, IL-6, IL-1beta, TNF-alpha), apoptosis and oxidative
stress pathways. These findings suggest the use of 453 as a novel EGFR-inhibitor
for therapeutic use in CKD kidney dysfunction.
PMID- 27497884
TI - Silencing of hypoxia inducible factor-1alpha gene attenuated angiotensin II
induced abdominal aortic aneurysm in apolipoprotein E-deficient mice.
AB - BACKGROUND AND AIMS: We aimed to determine the effect of HIF-1alpha, the main
regulatory subunit of the hypoxia inducible factor 1 (HIF-1), on the development
of the abdominal aortic aneurysm (AAA). METHODS: AAA was induced in ApoE(-/-)
mice by angiotensinII (AngII) infusion. In vivo silencing of HIF-1alpha was
achieved by transfection of lentivirus expressing HIF-1alpha shRNA. RESULTS: Time
course analysis of the AngII infusion model revealed that HIF-1alpha was
persistently upregulated during a 28-day period of AAA development. Silencing of
the HIF-1alpha gene reduced the aneurysm size (2.84 +/- 1.96 mm vs. 1.41 +/- 0.85
mm respectively at day 28, p = 0.0002). Silencing of HIF-1alpha also alleviated
infiltration of macrophages (38.8 +/- 14.7 vs. 11.4 +/- 4.4 macrophages/0.1
mm(2), p = 0.0006) and neovascularity (5.56 +/- 2.14 vs. 1.27 +/- 1.05
microvessels/0.1 mm(2), p = 0.0008) in the AngII infusion model, at day 28. The
activity of MMP-2 and MMP-9 was also decreased by knockdown of HIF-1alpha. The
early increased expression of pro-inflammatory factors, angiogenic factors, and
MMPs during AAA induction was alleviated by HIF-1alpha silencing. CONCLUSIONS:
Activation of HIF-1 signaling pathway participates in the Ang II-induced AAA
formation in mice.
PMID- 27497886
TI - A systematic review of preoperative predictors for postoperative clinical
outcomes following lumbar discectomy.
AB - BACKGROUND CONTEXT: Sciatica is often caused by a herniated lumbar intervertebral
disc. When conservative treatment fails, a lumbar discectomy can be performed.
Surgical treatment via lumbar discectomy is not always successful and may depend
on a variety of preoperative factors. It remains unclear which, if any,
preoperative factors can predict postsurgical clinical outcomes. PURPOSE: This
review aimed to determine preoperative predictors that are associated with
postsurgical clinical outcomes in patients undergoing lumbar discectomy. STUDY
DESIGN: This is a systematic review. METHODS: This systematic review of the
scientific literature followed the Preferred Reporting Items for Systematic
Review and Meta-Analysis guidelines. MEDLINE and PubMed were systematically
searched through June 2014. Results were screened for relevance independently,
and full-text studies were assessed for eligibility. Reporting quality was
assessed using a modified Newcastle-Ottawa Scale. Quality of evidence was
assessed using a modified version of Sackett's Criteria of Evidence Support. No
financial support was provided for this study. No potential conflict of interest
associated biases were present from any of the authors. RESULTS: The search
strategy yielded 1,147 studies, of which a total of 40 high-quality studies were
included. There were 17 positive predictors, 20 negative predictors, 43 non
significant predictors, and 15 conflicting predictors determined. Preoperative
predictors associated with positive postoperative outcomes included more severe
leg pain, better mental health status, shorter duration of symptoms, and younger
age. Preoperative predictors associated with negative postoperative outcomes
included intact annulus fibrosus, longer duration of sick leave, worker's
compensation, and greater severity of baseline symptoms. Several preoperative
factors including motor deficit, side and level of herniation, presence of type 1
Modic changes and degeneration, age, and gender had non-significant associations
with postoperative clinical outcomes. CONCLUSIONS: It may be possible for certain
preoperative factors to be targeted for clinical evaluation by spine surgeons to
assess the suitability of patients for lumbar discectomy surgery, the hope being
to thereby improve postoperative clinical outcomes. Prospective cohort studies
are required to increase the level of evidence with regard to significant
predictive factors.
PMID- 27497885
TI - Different end-points to assess effects in systemic lupus erythematosus patients
exposed to pesticide mixtures.
AB - Systemic Lupus Erythematosus (SLE) is an autoimmune disease with high female
predominance in reproductive years. It is characterized by a pronounced
inflammation and production of a variety of autoantibodies. SLE pathogenesis is
influenced by genes, hormones and environmental agents. The aim of this study was
assess the possible effect of environmental pesticide mixtures in SLE patients.
Oxidative DNA damage was measured using the comet assay modified by enzyme Endo
III for detection of oxidized bases (Endo Sites), and oxidative stress by the
measurement of the activity of catalase (CAT), superoxide dismutase (SOD) and
lipid peroxidation (TBARS). Eighty-nine patients with diagnosis of SLE were
included, 46% of them came from areas highly sprayed with pesticides and were
compared with patients from urban areas with the same clinical and socio
demographic characteristics (p>=0.155). In order to identify factors that could
predict DNA damage and oxidative stress, a binary logistic regression model with
independent variables was developed: place of residence (p=0.007) have 75% of
positive predictive value while smoking habit (p=0.186) have a 56% negative
predictive value. The Odd Ratio (OR) obtained indicate that lupus patients living
in rural areas presented 3.52 times more oxidative DNA damage compared to those
living in the city. The prospects of applying biomarkers to assess exposure and
biological effects, such as DNA damage and oxidative stress in autoimmune
diseases, allow improving the characterization of individual risk.
PMID- 27497887
TI - Insurance status and reportable quality metrics in the cervical spine fusion
population.
AB - BACKGROUND CONTEXT: The incidence of adverse care quality events among patients
undergoing cervical fusion surgery is unknown using the definition of care
quality employed by the Centers for Medicare and Medicaid Services (CMS). The
effect of insurance status on the incidence of these adverse quality events is
also unknown. PURPOSE: This study determined the incidence of hospital-acquired
conditions (HAC) and patient safety indicators (PSI) in patients with cervical
spine fusion and analyzed the association between primary payer status and these
adverse events. STUDY DESIGN: This is a retrospective cohort design. PATIENT
SAMPLE: All patients in the Nationwide Inpatient Sample (NIS) aged 18 and older
who underwent cervical spine fusion from 1998 to 2011 were included. OUTCOME
MEASURES: Incidence of HAC and PSI from 1998 to 2011 served as outcome variables.
METHODS: We queried the NIS for all hospitalizations that included a cervical
fusion during the inpatient episode from 1998 to 2011. All comparisons were made
between privately insured patients and Medicaid or self-pay patients because
Medicare enrollment is confounded with age. Incidence of nontraumatic HAC and PSI
was determined using publicly available lists of International Classification of
Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. We
built logistic regression models to determine the effect of primary payer status
on PSI and nontraumatic HAC. RESULTS: We identified 419,424 hospitalizations with
cervical fusion performed during an inpatient episode. The estimated national
incidences of nontraumatic HAC and PSI were 0.35% and 1.6%, respectively. After
adjusting for patient demographics and hospital characteristics, Medicaid or self
pay patients had significantly greater odds of experiencing one or more HAC (odds
ratio [OR] 1.51 95% conflict of interest [CI] 1.23-1.84) or PSI (OR 1.52 95% CI
1.37-1.70) than the privately insured cohort. CONCLUSIONS: Among patients
undergoing inpatient cervical fusion, primary payer status predicts PSI and HAC
(both indicators of adverse health-care quality used to determine hospital
reimbursement by CMS). As the US health-care system transitions to a value-based
payment model, the cause of these disparities must be studied to improve the
quality of care delivered to vulnerable patient populations.
PMID- 27497888
TI - The fatty degeneration of lumbar paraspinal muscles on computed tomography scan
according to age and disc level.
AB - BACKGROUND CONTEXT: Spinal degeneration can occur not only in the bone and disc
but also in muscles. Fatty infiltration (FI) and decreased volume have been
described as characteristic changes that occur in muscle degeneration. Many
studies about the lumbar paraspinal muscles have been conducted on patients with
spine problems. However, the natural changes of age-dependent degeneration in the
paraspinal muscles have not been studied properly. PURPOSE: The purpose of this
study is to investigate age- and level-dependent changes of the lumbar paraspinal
muscles in the population without lumbar spinal symptoms. STUDY DESIGN: This
study is a retrospective case-control study. PATIENT SAMPLE: A total of 887
patients who underwent computed tomography scan for abdomen and pelvis (APCT)
between January 2013 and December 2013 were enrolled. After excluding 237
patients with medical history of spine surgery, low back pain, myopathy, muscular
dystrophy, infectious disease, vertebral fracture, and deformity, 650 patients
were finally subjected to this study. OUTCOME MEASURE: The patients were divided
into three age groups: young (20-39 years old), middle (40-59 years old), and old
(60-89 years old). The degree of FI was checked twice for multifidus muscle (MF),
erector spinae muscle (ES), and psoas muscle (PS) at each disc level from L1 to
S1 on APCT by two investigators. The FI was measured as the Hounsfield unit, a
mean density (MD) on CT. METHODS: The age differences were compared with the data
of the young group, and the level differences were compared with the data of the
L1-L2 level. Student t test and intraclass correlation coefficient were checked
for statistical analysis. RESULTS: The gender ratio was not significantly
different among the groups. Comparing with the young group, the MD of MF
significantly decreased at L5-S1 in the middle group (p<.05), and at L3-L4-L5-S1
in the old group (p<.05). The MD of ES was significantly decreased at all levels
in the old group (p<.05) but not significant in the middle group. Comparing with
the L1-L2 level, the MD of MF significantly decreased at L5-S1 in the middle
group (p<.05) and at L4-L5-S1 in the old group (p<.05). The MD of ES was
significantly decreased at L5-S1 in the young and middle groups (p<.05) and at L4
L5-S1 in the old group (p<.01) compared with those at L1-L2. According to the age
and level-dependent changes of MD in the MF and ES, there was a tendency of
progressive increase of FI in the muscles with age, which seemed to start from L5
S1 and spread to the upper levels. The age-dependent fatty degeneration appeared
wider in the ES than the MF. The level-dependent FI of the ES showed a similar
pattern with the MF, but the change of the ES seemed to start earlier in age than
the MF at the L5-S1. There was no significant MD change in the PS according to
age and level. Intraobserver and interobserver reliabilities were both high
across all of the muscles (0.86-0.94 and 0.83-0.92). CONCLUSIONS: As a result,
the degree of intramuscular fat infiltration seems to be affected by age, disc
level, and muscle type. It seems to be more prominent in the extensor muscles,
extending from lower to upper levels.
PMID- 27497889
TI - Frequent neuromonitoring loss during the completion of vertebral column
resections in severe spinal deformity surgery.
AB - BACKGROUND CONTEXT: Intraoperative monitoring (IOM) is an essential method for
preventing postoperative spinal deficits during posterior vertebral column
resection (VCR) surgery for treatment of severe spine deformities, but the IOM
features directing at VCR procedures are rarely reported and need to be further
clarified. PURPOSE: To evaluate an important surgical point that will lead to the
IOM loss frequently, and then remind the surgeons to pay close attention to
impending monitoring changes during posterior VCR surgery. STUDY DESIGN/SETTING:
Retrospective study. PATIENT SAMPLE: A total of 77 patients with severe spine
deformities who underwent posterior VCR and deformity correction surgeries from
January 2012 to May 2015 are retrospectively analyzed in our spine center.
OUTCOME MEASURES: IOM (motor-evoked potentials [MEP] and somatosensory-evoked
potentials) was used for intraoperative spinal function assessment. METHODS:
Patients were divided into 2 groups according to their preoperative spinal
function, including 27 patients with preoperative spinal deficits and 50 patients
with spinal normal. And the IOM data during surgery, especially among VCR
procedures, were mainly analyzed in the present study. RESULTS: With the VCR
procedure almost complete, most patients showed varying degrees of IOM loss that
included 37 cases showing obvious IOM degenerations and 21 cases showing
significant IOM loss with alerts immediately. Moreover, the patients with
preoperative spinal deficits have more significant decreasing percentage in MEP
amplitude (81% vs. 68%, p<.05) than those patients without. CONCLUSIONS: With the
VCR procedure almost complete, surgeons must pay closely attention to the IOM
signals and should be ready to take corresponding surgical measures to deal with
the impeding monitoring loss.
PMID- 27497890
TI - Effectiveness of physiotherapy for seniors with recurrent headaches associated
with neck pain and dysfunction: a randomized controlled trial.
AB - BACKGROUND CONTEXT: A previous study demonstrated that in seniors, the presence
of cervical musculoskeletal impairment was not specific to cervicogenic headache
but was present in various recurrent headache types. Physiotherapy treatment is
indicated in those seniors diagnosed with cervicogenic headache but could also be
adjunct treatment for those with cervical musculoskeletal signs who are suspected
of having transitional headaches. PURPOSE: This study aimed to determine the
effectiveness of a physiotherapy program for seniors with recurrent headaches
associated with neck pain and cervical musculoskeletal dysfunction, irrespective
of the headache classification. STUDY DESIGN: This is a prospective, stratified,
randomized controlled trial with blinded outcome assessment. PATIENT SAMPLE:
Sixty-five participants with recurrent headache, aged 50-75 years, were randomly
assigned to either a physiotherapy (n=33) or a usual care group (n=32). OUTCOME
MEASURES: The primary outcome was headache frequency. Secondary outcomes were
headache intensity and duration, neck pain and disability, cervical range of
motion, quality of life, participant satisfaction, and medication intake.
METHODS: Participants in the physiotherapy group received 14 treatment sessions.
Participants in the usual care group continued with their usual care. Outcome
measures were recorded at baseline, 11 weeks, 6 months, and 9 months. This study
was funded by a government research fund of $6,850. No conflict of interest is
declared. RESULTS: There was no loss to follow-up for the primary outcome
measure. Compared with usual care, participants receiving physiotherapy reported
significant reductions in headache frequency immediately after treatment (mean
difference -1.6 days, 95% confidence interval [CI] -2.5 to -0.6), at 6-month
follow-up (-1.7 days, 95% CI -2.6 to -0.8), and at 9-month follow-up (-2.4 days,
95% CI -3.2 to -1.5), and significant improvements in all secondary outcomes
immediately posttreatment and at 6- and 9-month follow-ups, (p<.05 for all). No
adverse events were reported. CONCLUSIONS: Physiotherapy treatment provided
benefits over usual care for seniors with recurrent headache associated with neck
pain and dysfunction.
PMID- 27497891
TI - Are Modic changes associated with intervertebral disc cytokine profiles?
AB - BACKGROUND CONTEXT: Degenerative changes including Modic changes (MCs) are
commonly observed in patients with chronic low back pain. Although intervertebral
disc (IVD) cytokine expression has been shown to be associated with low back
pain, the cytokine profile for degenerative IVD with and without MC has not been
compared. PURPOSE: This study aimed to evaluate the potential association between
IVD cytokine expression and MCs. STUDY DESIGN: A laboratory study was carried
out. METHODS: The IVD tissue samples from 10 patients with type II MCs and10
patients without MCs who underwent an anterior lumbar interbody and fusion for
significant low back pain were collected. The expression levels of 42 cytokines
were determined using a RayBio Human Cytokine Antibody Array 3 (RayBiotech Inc,
Norcross, GA, USA) and the results were verified with enzyme-linked immunosorbent
assay (ELISA). RESULTS: The cytokine array demonstrated a statistically
significant increase in the expression of granulocyte-macrophage colony
stimulating factor (GM-CSF) (p=.001) and epithelial-derived neutrophil-activating
peptide 78 (ENA-78) (p=.04), and a trend toward an increase in interleukin-1beta
(IL-1beta) (p=.12) and tumor necrosis factor-alpha (TNF-alpha) (p=.22) in IVDs
associated with type II MCs. These results were validated with ELISA which
demonstrated a 3.85-fold increase in the GM-CSF level between IVDs with type II
MCs compared with those without MCs (p=.03). Similarly there was a significant
increase in the level of both ENA-78 (3.68-fold, p=.02) and IL-1beta (2.11-fold,
p=.01) in IVDs with type II MCs. Lastly, there was a trend (p=.07) toward an
increase in TNF-alpha in IVDs with type II MCs (4.4-fold). CONCLUSION:
Intervertebral discs with type II MCs demonstrate a significant increase in IL
1beta, GM-CSF, and ENA-78, and there is a trend toward an increase in TNF-alpha.
These results further strengthen the association between MCs and low back pain.
PMID- 27497892
TI - Pathogenesis of Photobacterium damselae subspecies infections in sea bass and sea
bream.
AB - Photobacterium damselae is a Gram negative bacterium causes photobacteriosis, a
worldwide septicemic disease in aquaculture including sea bass (Dicentrarchus
labrax) and sea bream (Sparus aurata). The pathogenicity of bacterial subspecies
and the disease pathological changes in natural and experimental infections have
thus far yielded inconsistency of effective preventive measures. This study aimed
to represent a comprehensive analysis of the potential pathogenic capacities of
the two subspecies of P. damselae in cultured sea bass and sea bream in the
Northwestern region of Egypt. Diseased 321 sea bass and 257 sea bream, in
addition to 99 healthy sea bass fingerlings were sampled from three farms located
along the Mediterranean Sea. P. damselae subspecies were isolated from diseased
fish and characterized using bacteriological, molecular, and antimicrobial
susceptibility methods. Healthy fish were challenged by a virulent P. damselae
subsp. piscicida, monitored for disease signs and mortality, and the
histopathological abnormalities and hematological disorders were carried out.
Clinical signs and gross lesions in naturally infected sea bass and sea bream
showed great similarities with absence of a subspecies-specific characteristic
sign or lesion. The two subspecies were recovered through the entire year from
individual fish sample, suggests a coexistence of two subspecies endemic
infection. In diseased sea bass, 38.32% and 16.20% were positive for P. damselae
subsp. piscicida and subsp. damselae, respectively. However in diseased sea
bream, 44.47% and 26.46% were positive for P. damselae subsp. piscicida and
subsp. damselae, respectively. High mortalities and devastating clinicopathologic
abnormalities represented by sever clinical signs, hematological disorders and
histological abnormalities strengthen the pathogenicity of P. damselae subspecies
in the two fish species and therefore, a vaccination strategy against both
subspecies should be taken into account.
PMID- 27497893
TI - Molecular characterization of genotype XIIIb Newcastle disease virus from central
India during 2006-2012: Evidence of its panzootic potential.
AB - Newcastle disease virus (NDV) is the causative agent of Newcastle disease (ND) in
many avian species. ND is a serious problem in developing countries, causing huge
loss in the poultry industry. Although there are reports of continuous outbreaks
of ND leading to serious losses to the poultry farming, very less is known about
the genetic characteristics of its strains circulating in different parts of
India. In the present study, we have five isolates of NDV reported from different
outbreaks in Central India between the years 2006-2012. Deduced amino acid
sequence of the F protein cleavage site and phylogenetic analysis of all the five
isolates showed circulation of NDV genotype XIIIb. All the isolates showed a
unique virulent cleavage site 112RRQKR?F117. The close genetic similarity of all
the isolates suggested circulation of the virulent NDV strains of the same
ancestor in and around central India. Continuous isolation of genotype XIIIb NDV
strains within the country suggests its panzootic potential. The study will be
useful to understand the circulating strains of NDV and plan a vaccination
strategy for poultry in India.
PMID- 27497894
TI - Antimicrobial and enhancement of the antibiotic activity by phenolic compounds:
Gallic acid, caffeic acid and pyrogallol.
AB - The indiscriminate use of antimicrobial drugs has increased the spectrum of
exposure of these organisms. In our studies, these phenolic compounds were
evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial,
antifungal and modulatory of antibiotic activities of these compounds were
assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to
bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was
made by comparisons of the MIC and MFC of the compounds alone and combined with
drugs against bacteria and fungi respectively, using a sub-inhibitory
concentration of 128 MUg/mL of substances (MIC/8). All substances not
demonstrated clinically relevant antibacterial activity with a MIC above >=1024
MUg/mL. As a result, we observed that the caffeic acid presented a potentiating
antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a
synergistic effect with two of the antibiotics tested, but only against
Staphylococcus aureus. In general, caffeic acid was the substance that presented
with the greatest number of antibiotics and with the greatest number of bacteria.
In relation to the antifungal activity of all the compounds, the verified results
were >=1024 MUg/mL, not demonstrating significant activity. Regarding
potentiation of the effect of fluconazole, was observed synergistic effect only
when assayed against Candida tropicalis, with all substances. Therefore, as can
be seen, the compounds presented as substances that can be promising potentiating
agents of antimicrobial drugs, even though they do not have direct antibacterial
and antifungal action.
PMID- 27497895
TI - Performance of Holstein calves fed whole milk with or without kefir.
AB - A growing body of evidence suggests health-promoting effects of kefir consumption
on different nonruminant species, leading to the speculation that kefir may act
as a probiotic and benefit calf performance and health. Our objectives were to
determine effects of feeding kefir on performance and health of calves in the
first 70d of life. Thirty 3-d-old female Holstein calves (body weight=38.2+/
3.1kg) were blocked by initial body weight and assigned randomly to 1 of 3
treatments (1 calf per pen; 10 pens per treatment). Kefir was added to whole milk
(vol/vol) at 0:1 (control; KF0), 1:3 (KF1), or 1:1 (KF2) and fed twice per day
(0800 and 1600h) from d3 through 45 and then once per day until weaning, which
occurred on d50. Pre- and postweaning intake of starter, daily body weight gain,
and gain-to-feed ratio exhibited no difference among treatments. Adding kefir to
whole milk fed directly to calves had no effect on concentration of blood
metabolites collected on d20, 40, and 70. Body length on d50 (weaning) and 70 was
greater in kefir-fed calves. Kefir intake improved fecal scores and reduced days
with diarrhea during the first 2wk of life. Apparent digestibility of organic
matter, ether extract, crude protein, and neutral detergent fiber remained
unaffected by treatment. Overall, it appears that directly feeding kefir to
calves during the preweaning period did not improve the performance of calves
under the conditions of the current study; however, its consumption marginally
improved body length and fecal consistency in the first weeks of life, which is
an important concern in intensive calf-rearing systems. Feeding kefir to neonatal
calves may be a viable approach to improve the health of calves in commercial
calf-rearing operations, although to validate its health-promoting effects
additional research is needed to investigate its effects under different calf
rearing conditions.
PMID- 27497896
TI - Characterization of a heat-resistant extracellular protease from Pseudomonas
fluorescens 07A shows that low temperature treatments are more effective in
deactivating its proteolytic activity.
AB - This work discusses the biological and biochemical characterization of an
extracellular protease produced by Pseudomonas fluorescens. The enzyme has a
molecular weight of 49.486 kDa and hydrolyzes gelatin, casein, and azocasein, but
not BSA. Its maximum activity is found at 37 degrees C and pH 7.5, but it
retained almost 70% activity at pH 10.0. It was shown to be a metalloprotease
inhibited by Cu(2+), Ni(2+), Zn(2+), Hg(2+), Fe(2+), and Mg(2+), but induced by
Mn(2+). After incubation at 100 degrees C for 5min, the enzyme presented over 40%
activity, but only 14 to 30% when submitted to milder heat treatments. This
behavior may cause significant problems under conditions commonly used for the
processing and storage of milk and dairy products, particularly UHT milk. A
specific peptide sequenced by mass spectrometer analysis allowed the
identification of gene that encodes this extracellular protease in the genome of
Pseudomonas fluorescens 07A strain. The enzyme has 477 AA and highly conserved
Ca(2+)- and Zn(2+)-binding domains, indicating that Ca(2+), the main ion in milk,
is also a cofactor. This work contributes to the understanding of the biochemical
aspects of enzyme activity and associates them with its sequence and structure.
These findings are essential for the full understanding and control of these
enzymes and the technological problems they cause in the dairy industry.
PMID- 27497897
TI - Short communication: Mid-infrared spectroscopy prediction of fine milk
composition and technological properties in Italian Simmental.
AB - The objective of this study was to evaluate the ability of mid-infrared
predictions of fine milk composition and technological traits to serve as a tool
for large-scale phenotyping of the Italian Simmental population. Calibration
equations accurately predicted the fatty acid profile of the milk, but we
obtained moderate or poor accuracy for detailed protein composition, coagulation
properties, curd yield and composition, lactoferrin, and concentration of major
minerals. To evaluate the role of infrared predictions as indicator traits of
fine milk composition in indirect selective breeding programs, the genetic
parameters of the traits predicted using mid-infrared spectra need to be
estimated.
PMID- 27497898
TI - Short communication: Associations between blood fatty acids, beta
hydroxybutyrate, and alpha-tocopherol in the periparturient period in dairy cows:
An observational study.
AB - The objective of the present study was to examine the relationships between blood
concentrations of fatty acids, beta-hydroxybutyrate (BHB), and alpha-tocopherol
during the periparturient period in dairy cows. Blood samples were collected from
131 cows belonging to 4 different commercial dairy farms in southeastern Europe
(Greece and Italy). We determined blood concentrations of fatty acids, BHB, and
alpha-tocopherol at dry-off, at calving, and 30d postpartum. Results indicated
that fatty acid concentrations were low at dry-off, reached maximum value at
calving, and then declined at 30d postpartum. In fact, fatty acid concentrations
at 30d postpartum were 50% lower than at calving. In contrast, BHB concentrations
were low at dry-off, increased by 27% at calving, and continued to increase by
another 20% at 30d postpartum. Overall, we found a weak correlation between fatty
acids and BHB throughout the periparturient period. Concentrations of alpha
tocopherol were lowest at calving, and we detected no differences in alpha
tocopherol concentrations at dry-off or 30d postpartum. Negative correlations
between fatty acids and alpha-tocopherol were highly significant at 30d
postpartum and approached the level of significance at dry-off. However, both
correlations became nonsignificant following the adjustment of alpha-tocopherol
with cholesterol, indicating that the correlations were a reflection of changes
in lipid transport. We found significant negative correlations (strong at dry-off
and weak at 30d postpartum) between BHB and alpha-tocopherol after adjustment
with cholesterol. The physiological basis for the negative correlations between
BHB and alpha-tocopherol, especially that at dry-off, is not known and should not
be taken to imply a cause-effect relationship. However, it opens the door to
investigating the effects of vitamin E on liver function in dairy cows.
PMID- 27497899
TI - Effects of air exposure, temperature and additives on fermentation
characteristics, yeast count, aerobic stability and volatile organic compounds in
corn silage.
AB - Ensiling conditions strongly influence fermentation characteristics, yeast count,
and aerobic stability. Numerous volatile organic compounds including esters are
produced, which may negatively affect feed intake and animal performance and air
quality. In addition to a farm survey, 3 laboratory experiments were carried out
to study the effects of air (by delayed sealing or by air infiltration during
anaerobic storage), temperature (20 and 35 degrees C), and various types of
additives [blends of either sodium benzoate and sodium propionate (SBSP) or of
sodium benzoate and potassium sorbate (SBPS); buffered mixture of formic and
propionic acids (FAPA); homofermentative inoculant (LAB)]. After additive
treatment, chopped whole corn plants were packed into 1.5-L glass jars and stored
for several months. For treatments with air infiltration, glass jars with holes
in the lid and body were used. The farm survey in 2009 revealed large variation
in lactate, acetate, ethanol, n-propanol, and 1,2-propanediol concentrations.
Whereas ethyl esters were detected in all silages, the mean ethyl lactate
concentrations were higher than those for ethyl acetate (474 vs. 38mg/kg of dry
matter). In the ensiling experiments, few unequivocal effects of the tested
factors on the analyzed parameters were observed due to many interactions.
Delayed ensiling without additives decreased lactic acid production but, in one
trial, increased acetic acid and had no effect on ethanol. The effect of delayed
sealing on yeast counts and aerobic stability differed widely among experiments.
Air infiltration during fermentation tested in one trial did not alter lactic
acid production, but resulted in more acetic acid in delayed and more ethanol
than in promptly sealed untreated silages. Greater ethanol production was
associated with increased yeast numbers. Storage at high temperature resulted in
lower lactic acid and n-propanol, and a trend toward reduced ethanol production
was observed. The additive FAPA consistently caused increased ethanol and reduced
n-propanol levels with no effect on yeast counts and aerobic stability. When the
additives SBSP and SBPS decreased n-propanol and ethanol, reduced yeast counts
were also found. Ethyl ester formation was strongly correlated with those of
ethanol and to a lesser degree with those of the respective acid.
PMID- 27497900
TI - Relative frequency of 4 major strain types of Mycobacterium avium ssp.
paratuberculosis in Canadian dairy herds using a novel single nucleotide
polymorphism-based polymerase chain reaction.
AB - Johne's disease is a worldwide concern, as it causes huge economic losses. The
etiological agent, Mycobacterium avium ssp. paratuberculosis (MAP), has limited
genetic diversity, impeding efforts to understand transmission and distribution
of strain types. Whole-genome sequencing was previously performed on a
representative set of MAP isolates from Canadian dairy herds and 9 divergent
clades were identified. Four clades were of particular interest, as they were
either MAP types rarely reported in North America, or they represented a
substantial proportion of isolates recovered from dairy farms in Canada. One
clade included type I/III isolates, whereas the remaining clades included type II
isolates. Variant sites in the MAP genome are often separated by thousands of
base pairs, limiting use of single nucleotide polymorphism (SNP)-based genotyping
on a single genomic region. Therefore, a SNP-PCR assay was developed to
facilitate interrogation of 5 SNP in 2 distant regions of the genome, linking
them together in a single PCR reaction for subsequent Sanger sequencing. This
high-throughput assay enabled discrimination of 602 MAP isolates from 264 herds
(from all 10 provinces). More than 1 isolate was cultured from 133 herds, 14 of
which included multiple subtypes. A previously identified dominant type included
87% of isolates, whereas the Bison type was more widespread than previously
reported. The latter type and isolates from a second clade of interest were
overrepresented in Quebec and Saskatchewan, respectively. In conclusion, the
distribution and relative frequency of MAP subtypes within Canadian dairy herds
were assessed using a novel SNP-based typing assay. These findings will
contribute to understanding the clinical relevance and transmission dynamics of
MAP in this population and elsewhere.
PMID- 27497901
TI - Stochastic dynamic simulation modeling including multitrait genetics to estimate
genetic, technical, and financial consequences of dairy farm reproduction and
selection strategies.
AB - The objective of this study was to develop a daily stochastic dynamic dairy
simulation model that included multitrait genetics and to evaluate the effects of
reduced genetic models and various reproduction and selection strategies on the
genetic, technical, and financial performance of a dairy herd. The 12 correlated
genetic traits included in the 2014 lifetime net merit (NM$) index were modeled
for each animal. For each animal, a true breeding value (TBV) for each trait was
calculated as the average of the sire's and dam's TBV, plus a fraction of the
inbreeding and Mendelian sampling variability. Similarly, an environmental
component for each trait was calculated and was partitioned into a permanent and
a daily (temporary) effect. The combined TBV and environmental effects were
converted into the phenotypic performance of each animal. Hence, genetics and
phenotypic performances were associated. Estimated breeding values (EBV) were
also simulated. Genetic trends for each trait for the service sire were based on
expected trends in US Holsteins. Surplus heifers were culled based on various
ranking criteria to maintain a herd size of 1,000 milking cows. In the first 8
scenarios, culling of surplus heifers was either random or based on the EBV of
NM$. Four different genetic models, depending on the presence or absence of
genetic trends or genetic and environmental correlations, or both, were evaluated
to measure the effect of excluding multitrait genetics on animal performance. In
the last 5 scenarios, the full genetic model was used and culling of surplus
heifers was either random or based on the EBV of NM$ or the EBV of milk. Sexed
semen use and reliability of the EBV were also varied. Each scenario was
simulated for 15yr into the future. Results showed that genetic models without
all 12 genetic trends and genetic and environmental correlations provided biased
estimates of the genetic, technical, and financial performance of the dairy herd.
Average TBV of NM$ of all cows in the herd was $263 greater in yr 15 in a
scenario that combined sexed semen use in heifers and culling of surplus heifers
with the lowest EBV of NM$, compared with a scenario that used only conventional
semen and surplus heifers were culled randomly. The average TBV of daughter
pregnancy rate of all cows in the herd was 1.25 percentage points greater in yr
15 in a scenario that combined using sexed semen in heifers as well as culling of
surplus heifers ranked by EBV of NM$, compared with a scenario using conventional
semen only as well as culling surplus heifers ranked by EBV of milk. In
conclusion, the multitrait genetics model resulted in improved estimates of
genetic, technical, and financial effects and appears useful to evaluate
consequences of various reproduction and selection strategies within a dairy
farm.
PMID- 27497902
TI - Effect of milk replacer program on calf performance and digestion of nutrients in
dairy calves to 4 months of age.
AB - Calves fed >0.7kg of dry matter from milk replacer (MR) typically have greater
growth preweaning but lower growth postweaning. This is partially explained by
lower digestibility of starter due to less development of the rumen at and after
weaning; however, it is unclear when digestibility matures postweaning to levels
typical of mature ruminants. Thus, we fed Holstein calves (initially 2 to 3d of
age) 3 MR programs (MOD=0.66kg daily for 39d, and then 0.33kg daily for 3d, n=15
calves; HIMOD=0.88kg daily for 5d, then 1.1kg daily for 23d, then 0.66kg daily
for 18d, and then 0.33kg daily for 3d, n=16 calves; HI=0.88kg daily for 5d, then
1.1kg daily for 37d, and then 0.56kg daily for 7d, n=15 calves). The MR consisted
of 28% crude protein and 20% fat and was reconstituted to 14% solids and fed at
0630 and 1400 h daily. A 39% starch textured starter (19% crude protein) was fed
free-choice for the first 56d of a nursery trial with calves in individual pens.
From 56 to 112d, calves were grouped by MR program into pens of 3 to 4 calves and
offered a starter with the same ingredient composition blended with 5% chopped
grass hay for ad libitum consumption. Digestion was estimated at 11 and 16wk.
Measurements in the first and second 56d were analyzed separately in a completely
randomized design using repeated measurements when applicable. Preplanned
contrasts of MOD versus HIMOD and MOD versus HI were used to separate means. Milk
replacer dry matter intake was 26.6, 42.4, and 48.7kg in calves fed MOD, HIMOD,
and HI, respectively. Starter intake was less for calves fed HIMOD and HI versus
MOD from 3 to 8wk. Efficiency of metabolizable energy and protein used for body
weight gain did not differ among programs. During the second 56d, body weight
gain and hip width changes were greater for calves fed MOD than HI. Total 112-d
body weight gain and total hip width changes were 101.4, 101.3, and 101.7kg, and
9.0, 9.1, and 8.7cm for MOD, HIMOD, and HI, respectively. Digestibility of all
nutrients except starch were greater at 16 versus 11wk of age. Digestibility of
dry matter, organic matter, neutral detergent fiber, and acid detergent fiber
were less for HI versus MOD at 11wk of age explaining much of the why postweaning
body weight gain advantages were lost postweaning in calves fed the HI program.
Feeding more than 0.66kg of dry matter intake from a MR during the preweaning
phase did not increase total body weight or hip width gain from 0 to 4mo of age.
PMID- 27497903
TI - The effect of conjugated linoleic acid supplements on oxidative and antioxidative
status of dairy cows.
AB - Dairy cows develop frequently negative energy balance around parturition and in
early lactation, resulting in excessive mobilization of body fat and subsequently
in increased risk of ketosis and other diseases. Dietary conjugated linoleic acid
(CLA) supplements are used in dairy cows mainly for their depressing effect on
milk fat content, but are also proposed to have antioxidative properties. As
negative energy balance is associated with oxidative stress, which is also
assumed to contribute to disease development, the present study was conducted to
examine effects of CLA on oxidative and antioxidative status of lactating dairy
cows. German Holstein cows (primiparous n=13, multiparous n=32) were divided into
3 dietary treatment groups receiving 100g/d of control fat supplement, containing
87% stearic acid (CON; n=14), 50g/d of control fat supplement and 50g/d of CLA
supplement (CLA 50; n=15), or 100g/d of CLA supplement (CLA 100; n=16). The CLA
supplement was lipid-encapsulated and contained 12% of trans-10,cis-12 CLA and
cis-9,trans-11 CLA each. Supplementation took place between d1 and 182
postpartum; d 182 until 252 postpartum served as a depletion period. Blood was
sampled at d -21, 1, 21, 70, 105, 140, 182, 224, and 252 relative to calving. The
antioxidative status was determined using the ferric-reducing ability of plasma,
alpha-tocopherol, alpha-tocopherol-to-cholesterol mass ratio, and retinol. For
determination of oxidative status concentrations of hydroperoxides,
thiobarbituric acid-reactive substances (TBARS), N'-formylkynurenine, and
bityrosine were measured. Mixed models of fixed and random effects with repeated
measures were used to evaluate period 1 (d -21 to 140) and 2 (d182-252)
separately. Cows showed increased oxidative stress and lipid peroxidation during
the periparturient period in terms of increased serum concentrations of
hydroperoxides and TBARS, which decreased throughout lactation. During period 1,
the supplemented cows had lower TBARS concentrations, which was not detectable in
period 2. The other determined parameters were not affected by CLA
supplementation. The obtained results show that dietary CLA supplementation in
the chosen dosage, formulation, and application period had a marginal
antioxidative effect in terms of lipid peroxidation in lactating dairy cows.
PMID- 27497904
TI - Temporal dominance of sensations sensory profile and drivers of liking of
artisanal Minas cheese produced in the region of Serra da Canastra, Brazil.
AB - The Serra da Canastra region, located in southwestern Minas Gerais, Brazil, is
recognized worldwide for its tradition of producing artisanal cheeses. However,
as production is done by hand, great variability exists in the characteristics of
artisanal Minas cheese. Thus, it is important to characterize the sensory profile
of these products and verify the quality attributes that lead to their
acceptance. Therefore, this study aimed to characterize the dynamic sensorial
profile of artisanal Minas cheese produced in the Serra da Canastra region
through temporal dominance of sensations and sensory acceptance tests and verify
the attributes that lead to product quality. We observed that the texture and
flavor profile varied among the evaluated artisanal Minas cheeses from Serra da
Canastra, some cheeses being more characterized by creamy and soft or hard and
firm sensations, whereas others had high dominance rates for crumbly texture. In
relation to flavor, salty and bitter tastes were dominant in most cheeses, some
also being characterized by a sour taste, and others by buttery and rancid
attributes, which indicates a lack of product standardization. However, all
samples obtained scores between 6 (liked slightly) and 7 (liked moderately),
indicating good acceptability in relation to the texture and flavor of the
evaluated cheeses. Moreover, it is possible to infer that creamy and soft or hard
and firm are positive attributes for cheese texture, and bitter, buttery, salty,
and acid taste drive cheese acceptance. This study provides important information
for product standardization, quality improvement, and process origin indications,
besides providing quality attributes that meet consumer desires.
PMID- 27497905
TI - Isolation of RNA from milk somatic cells as an alternative to biopsies of mammary
tissue for nutrigenomic studies in dairy ewes.
AB - Nutrigenomic studies of mammary lipogenesis in ruminants often rely on the use of
mammary tissue (MT) collected either by biopsy or at slaughter. However,
isolating RNA from milk would be a useful and cost-effective technique that may
avoid distress to the animal and facilitate the collection of samples in time
series experiments. This assay was therefore conducted to test the hypothesis
that RNA extracted from milk somatic cells (MSC) in dairy sheep would be a
feasible alternative to the performance of MT biopsies for nutrigenomic analyses.
To meet this objective, 8 lactating Assaf ewes were divided in 2 groups and
offered a total mixed ration without supplementation (control) or supplemented
with 2.4% dry matter of fish oil, which was known not only to elicit milk fat
depression but also to downregulate the expression of some candidate genes
involved in mammary lipogenesis. Total RNA was extracted from MSC and biopsied MT
to examine whether the potential changes in the abundance of transcripts was
similarly detected with both RNA sources. Milk fatty acid profile was also
analyzed by gas chromatography, and variations in mRNA abundance were determined
by reverse transcription quantitative PCR. Values of RNA integrity number were
always >=7.7. The expected and designed decrease of milk fat concentration with
fish oil (-29%), was associated with a lower transcript abundance of genes coding
for enzymes involved in fatty acid activation (ACSS1), de novo synthesis (ACACA
and FASN), uptake from plasma lipids (LPL), and esterification of fatty acids to
glycerol (LPIN1), as well as of a transcription factor that may regulate their
expression (INSIG1). Stable mRNA levels were showed in other candidate genes,
such as FABP3, GPAT4, or SCD. Changes due to the dietary treatment were similarly
detected with both RNA sources (MSC and MT biopsies), which supports the initial
hypothesis and would validate the use of milk as an alternative RNA source for
nutrigenomic analyses in dairy sheep.
PMID- 27497906
TI - Effects of pregrazing herbage mass in late spring on enteric methane emissions,
dry matter intake, and milk production of dairy cows.
AB - Few studies have examined the effects of fresh forage quality on enteric methane
(CH4) emissions of dairy cows under grazing conditions. The aim of the current
study was to evaluate the effects of 2 contrasting forage qualities induced by
different pregrazing herbage masses in late spring on enteric CH4 emissions and
milk production of grazing dairy cows. The experiment was conducted as a
crossover design with 24 lactating Holstein Friesian dairy cows randomly assigned
to 1 of 2 treatments in 2 experimental periods. Each period had a duration of 3wk
(2wk for diet adaptation and 1wk for measurements), and the interval between them
was 2wk. Treatments consisted of 2 target pregrazing herbage masses [2,200 and
5,000kg of dry matter (DM)/ha above 3cm], generated by different regrowth
periods, corresponding to low (LHM) and high (HHM) herbage mass treatments,
respectively. Daily herbage allowance (Lolium perenne) for both treatments was
20kg of DM per cow measured above 3cm. Enteric CH4 emissions were individually
determined during the last week of each period using the sulfur hexafluoride
tracer technique. Daily herbage intakes by individual cows during the CH4
measurement weeks were estimated using the n-alkanes technique. During the CH4
measurement weeks, milk yield and body mass were determined twice daily, whereas
milk composition was determined once in the week. The LHM pasture had a higher
crude protein concentration, lower neutral detergent fiber and acid detergent
fiber concentrations, and higher in vitro digestibility, with a lower proportion
of ryegrass pseudostems, than the HHM pasture. Cows offered the LHM pasture had
greater herbage (+13%) and total DM (+12%) intakes, increased milk (+13%) and
energy-corrected milk (+11%) yields, and tendencies toward higher milk protein
(+4.5%) and higher milk urea nitrogen (+15%) concentrations than their
counterparts offered the HHM pasture. No differences were found between
treatments in total daily CH4 production. However, the LHM treatment reduced
enteric CH4 emissions per unit of milk yield (-11%) and enteric CH4 energy as a
percentage of ingested gross energy (-9%) and tended to reduce CH4 per unit of
dry matter intake (-8.2%) and energy-corrected milk yield (-10%) compared with
the HHM treatment. The results from this study suggest that a grazing management
that favors better quality pasture, as was the case of the LHM pasture in late
spring compared with the HHM pasture, increases milk production of grazing dairy
cows and reduces enteric CH4 emissions per unit of milk produced, constituting a
viable CH4 mitigation strategy.
PMID- 27497907
TI - Development of a real-time PCR assay for direct detection and quantification of
Bacillus sporothermodurans in ultra-high temperature milk.
AB - In our study, a new and highly sensitive real-time PCR Taqman assay was developed
for the direct and specific detection of Bacillus sporothermodurans in UHT milk.
The target region was selected based on the 16S rRNA gene profiles of 11 B.
sporothermodurans from GenBank. A standard curve was created using a reference
strain of B. sporothermodurans, DSM 10599. A low limit of detection for B.
sporothermodurans in UHT milk (10 cfu/mL) was obtained. Furthermore, a total of
110 UHT milk samples from several supermarkets were directly assessed to detect
and quantify B. sporothermodurans using the real-time PCR Taqman developed. The
B. sporothermodurans counts obtained were highly correlated with the microbial
plate counts in the UHT milk samples. This is the first time that B.
sporothermodurans has been quantified directly from UHT milk. This technique
could be applicable as a routine tool for preventing the growth of these bacteria
by allowing for the rapid screening of raw milk samples in dairy plants. As
expected, the probability of bacterial growth in UHT milk packages increased with
the B. sporothermodurans counts in the raw milk.
PMID- 27497908
TI - Severe aortic arch calcification predicts mortality in patients undergoing
peritoneal dialysis.
AB - BACKGROUND/PURPOSE: Vascular calcification can predict cardiovascular (CV)
morbidity and mortality in patients with end-stage renal disease. We evaluated
the prevalence, association factors, and outcomes of chest X-ray-detected aortic
arch calcification (AoAC) in patients undergoing peritoneal dialysis (PD).
METHODS: We included 190 patients undergoing PD (mean age, 52.6 +/- 14.3 years)
for whom chest radiographs were available. AoAC revealed by chest X-ray was
graded from 0 to 3 according to an AoAC score (AoACS). Multiple regression
analyses were used to determine the factors associated with AoACS. After
adjusting for age, sex, PD duration, diabetes mellitus, mean blood pressure, and
history of CV disease, the association between AoAC grading and mortality were
assessed using the Kaplan-Meier curve and Cox proportional hazard model. RESULTS:
Age (p < 0.001), PD duration (p = 0.004), history of CV disease (p < 0.001), and
renal Kt/V (p = 0.031) were associated with AoACS. After a mean follow-up of 55.1
+/- 32.1 months, patients with Grade 2 (p = 0.011) or Grade 3 (p < 0.001) AoAC
had higher all-cause mortality than patients with Grade 0 AoAC. In addition,
patients with Grades 2 and 3 AoAC had higher CV-related mortality than those with
Grades 0 and 1 AoAC (p = 0.013). Grade 2 [hazard ratio (HR) = 2.736; 95%
confidence interval (CI), 1.038-7.211; p = 0.042] and Grade 3 AoAC (HR = 3.289;
95% CI, 1.156-9.359; p = 0.026) remained associated with all-cause mortality
after adjustment. Similarly, Grades 2 and 3 AoAC (HR = 36.05; 95% CI, 3.494-372;
p = 0.026) significantly correlated with CV mortality after adjustment.
CONCLUSION: In patients undergoing PD, CXR-detected severe AoAC was an
independent risk factor for all-cause and CV mortalities.
PMID- 27497909
TI - Mitochondrial H2O2 signaling is controlled by the concerted action of
peroxiredoxin III and sulfiredoxin: Linking mitochondrial function to circadian
rhythm.
AB - Mitochondria produce hydrogen peroxide (H2O2) during energy metabolism in most
mammalian cells as well as during the oxidation of cholesterol associated with
the synthesis of steroid hormones in steroidogenic cells. Some of the H2O2
produced in mitochondria is released into the cytosol, where it serves as a key
regulator of various signaling pathways. Given that mitochondria are equipped
with several H2O2-eliminating enzymes, however, it had not been clear how
mitochondrial H2O2 can escape destruction by these enzymes for such release.
Peroxiredoxin III (PrxIII) is the most abundant and efficient H2O2-eliminating
enzyme in mitochondria of most cell types. We found that PrxIII undergoes
reversible inactivation through hyperoxidation of its catalytic cysteine residue
to cysteine sulfinic acid, and that release of mitochondrial H2O2 likely occurs
as a result of such PrxIII inactivation. The hyperoxidized form of PrxIII (PrxIII
SO2H) is reduced and reactivated by sulfiredoxin (Srx). We also found that the
amounts of PrxIII-SO2H and Srx undergo antiphasic circadian oscillation in
mitochondria of the adrenal gland, heart, and brown adipose tissue of mice
maintained under normal conditions. Cytosolic Srx was found to be imported into
mitochondria via a mechanism that requires formation of a disulfide-linked
complex with heat shock protein 90, which is likely promoted by H2O2 released
from mitochondria. The imported Srx was found to be degraded by Lon protease in a
manner dependent on PrxIII hyperoxidation state. The coordinated import and
degradation of Srx underlie Srx oscillation and consequent PrxIII-SO2H
oscillation in mitochondria. The rhythmic change in the amount of PrxIII-SO2H
suggests that mitochondrial release of H2O2 is also likely a circadian event that
conveys temporal information on steroidogenesis in the adrenal gland and on
energy metabolism in heart and brown adipose tissue to cytosolic signaling
pathways.
PMID- 27497910
TI - The kinetics of angiotensin-I metabolism in human carotid atheroma: An emerging
role for angiotensin (1-7).
AB - AIM: Local levels of angiotensin peptides depend on their rates of production and
degradation, which induce proatherogenic or atheroprotective effects. Here, we
reveal the kinetics of Angiotensin-I metabolism in paired early and advanced
atherosclerotic lesions. METHODS: Lesions were spiked with labeled Ang-I* and
supernatants withdrawn after 0, 10, 20, 40 and 80min. The concentration of
produced Ang-II*, Ang-III*, Ang-IV* and Ang-(1-7)* peptides were measured using
multiple reaction monitoring mass spectrometry coupled to ultra-performance
liquid chromatography, normalized to tissue weight and initial [Ang-I*]. RESULTS:
Ang-(1-7)* was the major angiotensin peptide produced, showing increased levels
in both tissue types, with 2-3 fold lower levels in advanced compared to early
lesions. In contrast, Ang-II* was 2-3 fold higher in advanced compared to early
lesions, showing a decrease between 0 and 40min then an increase at 80min in both
tissue types. The levels of Ang-IV were stable in both tissue types across all
time points. Finally, Ang-III was non-detectable in both lesions across all time
points. CONCLUSION: Our results suggest that progression of atherosclerosis
depends on the increased levels of Ang-II along with the decreased levels of Ang
(1-7), which supports the use of Ang-(1-7) along with Angiotensin type-1 receptor
(AT1R) blockers.
PMID- 27497911
TI - Plasma MicroRNA-126-5p is Associated with the Complexity and Severity of Coronary
Artery Disease in Patients with Stable Angina Pectoris.
AB - BACKGROUND: Coronary artery disease (CAD) is a major problem worldwide. As an
endothelium-enriched microRNA (miRNA), miR-126 has been reported to serve as a
potential biomarker of acute myocardial infarction. However, the relationship
between miR-126 and the severity of CAD remains unknown. This study was designed
to test whether circulating miR-126 levels are associated with the severity of
CAD. METHODS: The present study enrolled 40 patients who had risk factors for CAD
without angiographically significant CAD, and 110 patients presenting with stable
angina pectoris, who were validated left main coronary artery disease (LMCA)
and/or multi-vessel disease by coronary angiography. The expression levels of
plasma miR-126-5p from all enrolled subjects were estimated by quantitative real
time polymerase chain reaction (qRT-PCR). Then, the relationships between plasma
miR-126-5p levels, number of diseased vessels and the corresponding Synergy
between PCI with Taxus and Cardiac surgery (SYNTAX) score were analyzed. RESULTS:
The expression of circulating miR-126-5p was affected by some CAD risk factors
including aging, dyslipidemia and DM. Furthermore, plasma miR-126-5p levels were
significantly down-regulated in CAD patients with multi-vessel disease, higher
SYNTAX score, rather than isolated LMCA and low SYNTAX score. CONCLUSION:
Circulating miR-126-5p has emerged as a potential biomarker for complexity and
severity of CAD in patients with stable angina pectoris.
PMID- 27497912
TI - Pulmonary involvement in systemic sclerosis.
AB - Systemic sclerosis (SSc) is a multi-systemic autoimmune disease that mainly
affects the skin, lungs, gastrointestinal tract, heart and kidneys. Pulmonary
disease in patients with SSc is strongly associated with mortality. The
mechanisms involved into its pathophysiology include the activation of autoimmune
cells and hyperplasia of fibroblasts with an increased capacity to produce
collagen and diminished collagen breakdown. Although pulmonary biopsy is the gold
standard for the diagnosis of interstitial lung disease in SSc, the most commonly
used method is high-resolution computed tomography due to its high sensitivity
and specificity. Herein, a comprehensive review on the pulmonary involvement in
SSc is presented highlighting the radiologic-pathologic correlations.
PMID- 27497913
TI - Parkinson's disease: Autoimmunity and neuroinflammation.
AB - Parkinson's disease is a neurodegenerative disease that causes the death of
dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency
in the basal ganglia leads to a movement disorder that is characterized by
classical parkinsonian motor symptoms. Parkinson's disease is recognized as the
most common neurodegenerative disorder after Alzheimer's disease. PD
ethiopathogenesis remains to be elucidated and has been connected to genetic,
environmental and immunologic conditions. The past decade has provided evidence
for a significant role of the immune system in PD pathogenesis, either through
inflammation or an autoimmune response. Several autoantibodies directed at
antigens associated with PD pathogenesis have been identified in PD patients.
This immune activation may be the cause of, rather than a response to, the
observed neuronal loss. Parkinsonian motor symptoms include bradykinesia,
muscular rigidity and resting tremor. The non-motor features include olfactory
dysfunction, cognitive impairment, psychiatric symptoms and autonomic
dysfunction. Microscopically, the specific degeneration of dopaminergic neurons
in the substantia nigra and the presence of Lewy bodies, which are brain deposits
containing a substantial amount of alpha-synuclein, have been recognized. The
progression of Parkinson's disease is characterized by a worsening of motor
features; however, as the disease progresses, there is an emergence of
complications related to long-term symptomatic treatment. The available therapies
for Parkinson's disease only treat the symptoms of the disease. A major goal of
Parkinson's disease research is the development of disease-modifying drugs that
slow or stop the neurodegenerative process. Drugs that enhance the intracerebral
dopamine concentrations or stimulate dopamine receptors remain the mainstay
treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to
attenuate PD neurodegeneration have become an attractive option and warrant
further investigation.
PMID- 27497914
TI - The importance of glial cells in the homeostasis of the retinal microenvironment
and their pivotal role in the course of diabetic retinopathy.
AB - Diabetic retinopathy (DR) is a remarkable microvascular complication of diabetes
and it has been considered the leading cause of legal blindness in working-age
adults in the world. Several overlapping and interrelated molecular pathways are
involved in the development of this disease. DR is staged into different levels
of severity, from the nonproliferative to the advanced proliferative form. Over
the years the progression of DR evolves through a series of changes involving
distinct types of specialized cells: neural, vascular and glial. Prior to the
clinically observable vascular complications, hyperglycemia and inflammation
affect retinal glial cells which undergo a wide range of structural and
functional alterations. In this review, we provide an overview of the status of
macroglia and microglia in the course of DR, trying to briefly take into account
the complex biochemical mechanisms that affect the intimate relationship among
neuroretina, vessels and glial cells.
PMID- 27497915
TI - What is herd immunity, and how does it relate to pediatric vaccination uptake? US
parent perspectives.
AB - In light of current concern over pediatric immunization rates, 53 US parents with
at least one child kindergarten age or younger were surveyed and interviewed
regarding vaccine decision making. Data were collected in 2014 in San Diego,
California. Herd immunity was not a salient issue: only six (11.3%) referenced
the term or concept spontaneously; others had to be prompted. Parents familiar
with herd immunity (70%) variously saw it as not just unnecessary but unproven,
illogical, unrealistic, and unreliable. For instance, parents questioned its
attainability because many adults do not immunize themselves. Some understood the
concept negatively, as an instance of "herd mentality." Further, having knowledge
of herd immunity that public health experts would deem 'correct' did not lead to
full vaccination. Implications of findings for understanding how the public makes
use of scientific information, the potential role of public health messaging
regarding altruism and 'free-riding,' and assumptions that vaccine-cautious
parents would willfully take advantage of herd immunity are explored in relation
to parent role expectations and American individualism.
PMID- 27497916
TI - From clinical sample to complete genome: Comparing methods for the extraction of
HIV-1 RNA for high-throughput deep sequencing.
AB - The BEEHIVE (Bridging the Evolution and Epidemiology of HIV in Europe) project
aims to analyse nearly-complete viral genomes from >3000 HIV-1 infected Europeans
using high-throughput deep sequencing techniques to investigate the virus genetic
contribution to virulence. Following the development of a computational pipeline,
including a new de novo assembler for RNA virus genomes, to generate larger
contiguous sequences (contigs) from the abundance of short sequence reads that
characterise the data, another area that determines genome sequencing success is
the quality and quantity of the input RNA. A pilot experiment with 125 patient
plasma samples was performed to investigate the optimal method for isolation of
HIV-1 viral RNA for long amplicon genome sequencing. Manual isolation with the
QIAamp Viral RNA Mini Kit (Qiagen) was superior over robotically extracted RNA
using either the QIAcube robotic system, the mSample Preparation Systems RNA kit
with automated extraction by the m2000sp system (Abbott Molecular), or the MagNA
Pure 96 System in combination with the MagNA Pure 96 Instrument (Roche
Diagnostics). We scored amplification of a set of four HIV-1 amplicons of ~1.9,
3.6, 3.0 and 3.5kb, and subsequent recovery of near-complete viral genomes.
Subsequently, 616 BEEHIVE patient samples were analysed to determine factors that
influence successful amplification of the genome in four overlapping amplicons
using the QIAamp Viral RNA Kit for viral RNA isolation. Both low plasma viral
load and high sample age (stored before 1999) negatively influenced the
amplification of viral amplicons >3kb. A plasma viral load of >100,000 copies/ml
resulted in successful amplification of all four amplicons for 86% of the
samples, this value dropped to only 46% for samples with viral loads of <20,000
copies/ml.
PMID- 27497917
TI - Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic
Skin.
AB - BACKGROUND: Psoriatic lesions may resolve with hypo- or hyperpigmentation. The
involvement of melanocytes in this dichotomous clinical outcome is not fully
investigated. OBJECTIVES: Qualitative and quantitative assessment of melanocytes
in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy
controls (n = 10). METHODS: Skin biopsies were labelled immunohistochemically
(APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45,
Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF).
The labelled melanocytes were evaluated by an independent investigator with a
digital image analyser. RESULTS: Lesional melanocytes, in contrast to those in
non-lesional and healthy skin, exhibited features of activation in the form of
dilatation, prominent and long dendrites and intense labelling. The number of
melanocytes was significantly increased in psoriatic lesions in comparison with
non-lesional psoriatic and healthy skin as shown by counts of cells labelled with
the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase
(1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant
difference (1.2-fold increase; p > 0.05). Likewise, no significant difference
between non-lesional psoriatic and healthy skin control was found (p > 0.05).
Furthermore, no positively labelled dermal cells were detected, apart from few
only detected with Melan A. CONCLUSIONS: Epidermal melanocyte activity and
numbers are increased in the epidermal compartment of psoriatic lesions providing
an explanation for postinflammatory hyperpigmentation.
PMID- 27497918
TI - Length of the memory retention period depends on the extent of protein synthesis
in the terrestrial slug Limax.
AB - The terrestrial slug Limax can form an odor-aversion memory by the single
simultaneous presentation of a food odor and an aversive stimulus. We have
previously demonstrated that the long-term retention of this memory was impaired
by a high-dose injection of a protein synthesis inhibitor 30min prior to the
conditioning. However, the onset of amnesia was delayed if the dose of the
inhibitor was reduced or a less potent protein synthesis inhibitor was used. We
thus speculated that the persistence of memory depends on the amount of newly
synthesized protein following learning. In the present study, we further
elaborated on this idea by injecting a high dose of anisomycin at different
timings before or after conditioning, and tested the memory retention at 1, 2, 3,
7, or 14days after the conditioning. We found that the injection of anisomycin 6h
before, or 1h after the conditioning had no effect on memory retention for 7days,
and an injection at 30min before and just following the conditioning impaired the
memory retention at 3days. Interestingly, the injection at 3h before and 30min
after the conditioning did not impair the retention at 3days but did impair
retention at 7days. Taking into account the time course of protein synthesis
inhibition in the brain, our results further support the idea that the memory
retention period is dependent on the amount of protein synthesized following
memory acquisition.
PMID- 27497919
TI - Salvianolic acid B improves the disruption of high glucose-mediated brain
microvascular endothelial cells via the ROS/HIF-1alpha/VEGF and miR-200b/VEGF
signaling pathways.
AB - The study investigated the roles and mechanisms of Salvianolic acid B (Sal B) on
permeability of rat brain microvascular endothelial cells (RBMECs) exposed to
high glucose. The results demonstrated that Sal B greatly up-regulated the
expression of tight junction (TJ) proteins and decreased the permeability of
RBMECs compared with the control group. And the increase of reactive oxidative
species (ROS) production, the upregulation of hypoxia-inducible factor-1 alpha
(HIF-1alpha) and vascular endothelial growth factor (VEGF) protein induced by
high glucose were antagonized by Sal B. In addition, a great decrease of microRNA
200b (miR-200b) was observed in the RBMECs under high-glucose condition, which
was significantly increased by Sal B pretreatment. And overexpression of miR-200b
markedly attenuated the RBMECs permeability and inhibited the expression of VEGF
protein by targeting with 3'-UTR of its mRNA. This led to the conclusion that Sal
B-mediated improvement of blood-brain barrier dysfunction induced by high-glucose
is related to the ROS/HIF-1alpha/VEGF and miR-200b/VEGF signaling pathways.
PMID- 27497920
TI - Acute single dose of ketamine relieves mechanical allodynia and consequent
depression-like behaviors in a rat model.
AB - Both chronic pain and depression are debilitating diseases, which often coexist
in clinic. However, current analgesics and antidepressants exhibit limited
efficacy for this comorbidity. The present study aimed to investigate the effect
of ketamine on the comorbidity of inflammatory pain and consequent depression
like behaviors in a rat model established by intraplantar administration of
complete Freunds adjuvant (CFA). The mechanical withdrawal threshold, thermal
withdrawal latency, open field test, forced swimming test, and sucrose preference
test were evaluated after the CFA injection and ketamine treatment. The
hippocampus was harvested to determine the levels of interleukin (IL)-6, IL
1beta, indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), 5-hydroxytryptamine
(5-HT), and tryptophan (TRP). The inflammatory pain-induced depression-like
behaviors presented on 7days and lasted to at least 14days after the CFA
injection. Single dose of ketamine at 20mg/kg relieved both the mechanical
allodynia and the associated depression-like behaviors as demonstrated by the
attenuated mechanical withdrawal threshold, reduced immobility time in the forced
swim test, and increased sucrose preference after ketamine treatment. The total
distance had no significant change after the CFA injection or ketamine treatment
in the open field test. Simultaneously, ketamine reduced the levels of IL-6, IL
1beta, IDO, and KYN/TRP ratio and increased the 5-HT/TRP ratio in the
hippocampus. In conclusion, acute single dose of ketamine can rapidly attenuate
mechanical allodynia and consequent depression-like behaviors and down-regulate
hippocampal proinflammatory responses and IDO/KYN signal pathway in rats.
PMID- 27497921
TI - Is there a generalized sweetness sensitivity for an individual? A psychophysical
investigation of inter-individual differences in detectability and
discriminability for sucrose and fructose.
AB - Despite the historical interest in the taste of sweetness, a seemingly
fundamental question has not been properly addressed. That is, whether an
individual's sensitivity can be generalized across different sugars. An answer to
this question has a close relevance to illuminating the sensory physiology of the
gustatory system, as well as to practical research of sucrose substitution. A
cross-disciplinary review highlights two weak links with the psychophysical
methods that have been employed in the literature. The present paper describes an
empirical investigation of inter-individual differences in detectability and
discriminability for two types of common sugars - sucrose and fructose, using
psychometric functions (PF) and a controlled sensory discrimination test. The
study found six of the 12 judges had significantly different thresholds for
sucrose and fructose (p<0.05), with no consistent pattern in the direction of
differences. This observation challenges the conventional belief that people hold
the same perception of relative difference in sweetness across substances. For
seven judges, the individually-fitted PFs exhibited different shapes for the
tested sugars, implying the detection processing might be substance-specific.
Also, inter-individual differences were observed in the controlled discrimination
task for sucrose and fructose at a supra-threshold level. These findings are
discussed in relation to their theoretical, practical and methodological values.
While this study uses sucrose and fructose as exemplars, the findings may provide
important insights into sweetness perception in general.
PMID- 27497922
TI - Voluntary running decreases nonexercise activity in lean and diet-induced obese
mice.
AB - PURPOSE: Determine whether voluntary wheel running triggers compensatory changes
in nonexercise activity in lean and high-fat diet fed mice. METHODS: C57Bl/6 mice
received a control (C) or a high-fat diet (H) and half of them had free access to
a running wheel 5days/week (CE and HE, respectively) for 10weeks. Energy intake,
nonexercise activity (global activity, distance covered and average speed of
displacement in the home cage) and energy expenditure (EE) were evaluated at
weeks 5 and 10 during the 2days without the wheels. RESULTS: High-fat diet
increased weight gain in H (110%) and HE (60%) groups compared to C and CE
groups, respectively, with no effect of exercise. Wheel running increased energy
intake (26% CE, 11% HE in week 5; 7% CE, 45% HE in week 10) and decreased
distance covered (26% for both CE and HE in week 5; 35% CE and 13% HE in week 10)
and average speed (35% CE and 13% HE in week 5; 45% CE and 18% HE in week 10)
compared to the respective nonexercised groups. In week 10 there was an
interaction between diet and exercise for global activity, which was reduced
nearly 18% in CE, H, and HE groups compared to C. Access to a running wheel
increased EE in week 5 (11% CE and 16% HE) but not in week 10, which is
consistent with the period of highest running (number of turns: weeks 1-5 nearly
100%>weeks 6-10 for CE and HE groups). EE was reduced in H (19%) and HE (12%)
groups compared to C and CE, in week 10. CONCLUSION: Voluntary running causes a
compensatory decrease in nonexercise activity and an increase in energy intake,
both contributing to the lack of effect of exercise on body mass.
PMID- 27497923
TI - Small field correction factors for the IBA Razor.
AB - The IBA Razor diode supersedes the IBA SFD and is intended for use in small
fields. However, its behaviour in small fields has not yet been quantified. In
this work, we examine the response of the Razor diode against the air core
scintillation dosimeter (FOD) and Gafchromic film in photon beams from three
Varian linac beams. Fields between 4mm and 30mm in width were measured, both with
and without a flattening filter and at two energies. The Razor exhibited an over
response of up to 4.5% for MLC collimated fields and 7.1% for stereotactic cone
collimated fields. The presence of the flattening filter altered the over
response by up to 1.5%. The small field correction factors are tabulated and
agree with the mathematical relation of Liu et al. (2014). Four samples of the
Razor were used, two having received a significant prior dose. The correction
factors for the four samples differed and may depend on their dose history.
PMID- 27497924
TI - Hyperphosphorylated tau in patients with refractory epilepsy correlates with
cognitive decline: a study of temporal lobe resections.
AB - SEE BERNASCONI DOI101093/AWW202 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE:
Temporal lobe epilepsy, the most prevalent form of chronic focal epilepsy, is
associated with a high prevalence of cognitive impairment but the responsible
underlying pathological mechanisms are unknown. Tau, the microtubule-associated
protein, is a hallmark of several neurodegenerative diseases including
Alzheimer's disease and chronic traumatic encephalopathy. We hypothesized that
hyperphosphorylated tau pathology is associated with cognitive decline in
temporal lobe epilepsy and explored this through clinico-pathological study. We
first performed pathological examination on tissue from 33 patients who had
undergone temporal lobe resection between ages 50 and 65 years to treat drug
refractory temporal lobe epilepsy. We identified hyperphosphorylated tau protein
using AT8 immunohistochemistry and compared this distribution to Braak patterns
of Alzheimer's disease and patterns of chronic traumatic encephalopathy. We
quantified tau pathology using a modified tau score created specifically for
analysis of temporal lobectomy tissue and the Braak staging, which was limited
without extra-temporal brain areas available. Next, we correlated tau pathology
with pre- and postoperative cognitive test scores and clinical risk factors
including age at time of surgery, duration of epilepsy, history of secondary
generalized seizures, history of head injury, handedness and side of surgery.
Thirty-one of 33 cases (94%) showed hyperphosphorylated tau pathology in the form
of neuropil threads and neurofibrillary tangles and pre-tangles. Braak stage
analysis showed 12% of our epilepsy cohort had a Braak staging III-IV compared to
an age-matched non-epilepsy control group from the literature (8%). We identified
a mixture of tau pathology patterns characteristic of Alzheimer's disease and
chronic traumatic encephalopathy. We also found unusual patterns of subpial tau
deposition, sparing of the hippocampus and co-localization with mossy fibre
sprouting, a feature of temporal lobe epilepsy. We demonstrated that the more
extensive the tau pathology, the greater the decline in verbal learning (Spearman
correlation, r = -0.63), recall (r = -0.44) and graded naming test scores (r =
0.50) over 1-year post-temporal lobe resection (P < 0.05). This relationship with
tau burden was also present when examining decline in verbal learning from 3
months to 1 year post-resection (r = -0.54). We found an association between
modified tau score and history of secondary generalized seizures (likelihood
ratio chi(2), P < 0.05) however there was no clear relationship between tau
pathology and other clinical risk factors assessed. Our findings suggest an
epilepsy-related tauopathy in temporal lobe epilepsy, which contributes to
accelerated cognitive decline and has diagnostic and treatment implications.
PMID- 27497925
TI - Spatiotemporal regulation of enhancers during cardiogenesis.
AB - With the advance in chromatin immunoprecipitation followed by high-throughput
sequencing, there has been a dramatic increase in our understanding of distal
enhancer function. In the developing heart, the identification and
characterisation of such enhancers have deepened our knowledge of the mechanisms
of transcriptional regulation that drives cardiac differentiation. With next
generation sequencing techniques becoming widely accessible, the quantity of data
describing the genome-wide distribution of cardiac-specific transcription factor
and chromatin modifiers has rapidly increased and it is now becoming clear that
the usage of enhancers is highly dynamic and complex, both during the development
and in the adult. The identification of those enhancers has revealed new insights
into the transcriptional mechanisms of how tissue-specific gene expression
patterns are established, maintained, and change dynamically during development
and upon physiological stress.
PMID- 27497927
TI - Long-term work participation among cystic fibrosis patients undergoing lung
transplantation.
AB - BACKGROUND: Patients with cystic fibrosis (CF) experience obstacles to
employment, regardless of whether they have undergone lung transplantation (LTx).
We investigated socioeconomic and clinical factors predicting long-term
employment outcomes in CF patients receiving LTx. METHODS: Data from the United
Network for Organ Sharing registry were used to identify CF patients 18-59years
old who received LTx between 2000 and 2010 and survived greater than 5years. Long
term employment status was determined by center-reported follow-up data on
patients working for income, collected at the 5th transplant anniversary. After
multiple imputation to complete missing data on covariates, multivariable
logistic regression was used to identify associations between characteristics at
or after LTx and long-term work participation. RESULTS: There were 745 patients
who met inclusion criteria and contributed employment data within 365days of
their 5th LTx anniversary. In this cohort, 48% (358/745) were working for income
5years after LTx. Younger age, male gender, better pulmonary function attained
post-transplant, pre-transplant work participation, and private health insurance
(compared to government Medicaid or Medicare insurance) at the time of transplant
predicted greater odds of post-transplant employment. CONCLUSIONS: Lack of work
experience and reliance on government health insurance at the time of transplant
predict lower long-term work participation among LTx recipients with CF. By
contrast, long-term employment outcomes were not negatively affected by
comorbidities at or after transplantation in this cohort. Despite resolving some
physiological obstacles to employment in patients with CF, LTx may introduce new
socioeconomic barriers to employment.
PMID- 27497928
TI - Magnetically Controlled Growing Rod in Early-Onset Scoliosis: A Minimum of 2-Year
Follow-Up.
AB - PURPOSE: The magnetically controlled growing rod technique decreases
complications, costs, and loss of functionality by avoiding successive surgical
corrections every 6 months in patients with early-onset scoliosis. However, only
a few studies have presented clinical experience with the magnetically controlled
growing rod. In this study we aimed to present our single-center experience in
patients with early-onset scoliosis who underwent the magnetically controlled
growing rod technique and follow-up for at least 2 years. MATERIALS AND METHODS:
We made an observational study by evaluating patients with early-onset scoliosis
who underwent the magnetically controlled growing rod technique between February
2012 and December 2013. Demographic and clinical data were obtained from the
patients charts. We included patients who were followed up for at least 2 years.
Radiological data were obtained from plain anterior-posterior and lateral
scoliosis X-rays. RESULTS: Eight patients with early-onset scoliosis who
underwent surgery using the magnetic system were treated with dual rods. None of
the spines were fused to the sacrum. We observed no intra- and/or postsurgical
complications. The average number of external rod lengthenings was 7.6. The
average amount of lengthening was 30.6 mm on the right side and 27.8 mm on the
left side by the time of last clinical follow-up. The average coronal and
sagittal Cobb values at the final clinical evaluation were 10.5 degrees
(thoracic coronal), 13.75 degrees (lumbar coronal), 6.25 degrees (lumbosacral
coronal), 24.5 degrees (thoracic sagittal), and 40 degrees (lumbar sagittal),
respectively. CONCLUSIONS: The magnetically controlled growing rod is beneficial
in early-onset scoliosis, since it enables spinal growth and decreases additional
surgeries, complications, and costs. Even though we had a small sample size, our
follow-up period was enough to declare long-term outcomes of our patients.
Multicenter and large sample-sized studies are needed to make more conclusive
statements regarding this promising scoliosis treatment approach.
PMID- 27497929
TI - Erratum to: Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients
with Mixed Hyperlipidemia.
PMID- 27497926
TI - Metazoan evolution of the armadillo repeat superfamily.
AB - The superfamily of armadillo repeat proteins is a fascinating archetype of
modular-binding proteins involved in various fundamental cellular processes,
including cell-cell adhesion, cytoskeletal organization, nuclear import, and
molecular signaling. Despite their diverse functions, they all share tandem
armadillo (ARM) repeats, which stack together to form a conserved three
dimensional structure. This superhelical armadillo structure enables them to
interact with distinct partners by wrapping around them. Despite the important
functional roles of this superfamily, a comprehensive analysis of the
composition, classification, and phylogeny of this protein superfamily has not
been reported. Furthermore, relatively little is known about a subset of ARM
proteins, and some of the current annotations of armadillo repeats are incomplete
or incorrect, often due to high similarity with HEAT repeats. We identified the
entire armadillo repeat superfamily repertoire in the human genome, annotated
each armadillo repeat, and performed an extensive evolutionary analysis of the
armadillo repeat proteins in both metazoan and premetazoan species. Phylogenetic
analyses of the superfamily classified them into several discrete branches with
members showing significant sequence homology, and often also related functions.
Interestingly, the phylogenetic structure of the superfamily revealed that about
30 % of the members predate metazoans and represent an ancient subset, which is
gradually evolving to acquire complex and highly diverse functions.
PMID- 27497930
TI - Pharmacological Agents Targeting Myocardial Metabolism for the Management of
Chronic Stable Angina : an Update.
AB - Despite continuous advances in myocardial revascularization procedures and
intracoronary devices, patients with ischemic heart disease (IHD) still
experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable
angina (CSA) is a common disease with a large burden on healthcare costs.
Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia
related to the presence of stable coronary artery plaque causing myocardial
demand/supply mismatch when myocardial oxygen consumption increases. Accordingly,
revascularization procedures are performed with the aim to remove the flow
limiting stenosis, whereas traditional medical therapy (hemodynamic agents) aims
at reducing myocardial oxygen demands. However, although effective, none of these
treatment strategies or their combination is either able to confer symptomatic
relief in all patients, nor to reduce mortality. Failure to significantly improve
QoL and prognosis may be attributed at least in part to this "restrictive"
understanding of IHD. Despite for many years myocardial metabolic derangement has
been overlooked, recently it has gained increased attention with the development
of new pharmacological agents (metabolic modulators) able to influence myocardial
substrate selection and utilization thus improving cardiac efficiency. Shifting
cardiac metabolism from free fatty acids (FA) towards glucose is a promising
approach for the treatment of patients with stable angina, independently of the
underling disease (macrovascular and/or microvascular disease). In this sense
cardiac metabolic modulators open the way to a "revolutionary" understanding of
ischemic heart disease and its common clinical manifestations, where myocardial
ischemia is no longer considered as the mere oxygen and metabolites demand/supply
unbalance, but as an energetic disorder. Keeping in mind such an alternative
approach to the disease, development of new pharmacological agents directed
toward multiple metabolic targets is mandatory.
PMID- 27497931
TI - A liquid crystal-based sensor for the simple and sensitive detection of cellulase
and cysteine.
AB - A liquid crystal (LC)-based sensor, which is capable of monitoring enzymatic
activity at the aqueous/LC interface and detecting cellulase and cysteine (Cys),
was herein reported. When functionalized with a surfactant, dodecyl beta-d
glucopyranoside, the 4-cyano-4'-pentylbiphenyl (5CB) displays a dark-to-bright
transition in the optical appearance for cellulase. We attribute this change to
the orientational transition of LCs, as a result of enzymatic hydrolysis between
cellulase and surfactant. Furthermore, by adding cellulase and Cu(2+), our
surfactant-LCs system performs an interesting ability to detect Cys, even though
Cys could not interact with surfactant or LC directly. Alternatively, through the
strong binding between Cys and Cu(2+), cellulase was able to hydrolyze surfactant
in the presence of Cu(2+), leading to the transition of LCs from dark to bright.
The detection limit of the LC sensor was around 1*10(-5)mg/mL and 82.5MUM for
cellulase and Cys, respectively. The LC-based sensor may contribute to the
development of low-cost, expedient, and label-free detection for cellulase and
Cys and the design strategy may also provide a novel way for detecting multiple
analytes.
PMID- 27497932
TI - Fluorescence labels may significantly affect the protein adsorption on
hydrophilic nanomaterials.
AB - Fluorescently labelled proteins are often used to study processes in vitro, e.g.
the binding of proteins to cell surfaces or the adsorption of plasma proteins on
drug nanocarriers. However, the fact that the fluorescent labelling may affect
the protein properties is frequently neglected. On the example of a simple model
system, we reiterate the importance of this issue by showing that even a single
label may perturb interactions between hydrophilic starch-based nanocapsules and
serum albumin and thus prevent binding.
PMID- 27497933
TI - Efficiency of emulsifier-free emulsions and emulsions containing rapeseed
lecithin as delivery systems for vectorization and release of coenzyme Q10:
physico-chemical properties and in vitro evaluation.
AB - To improve the encapsulation and release of coenzyme Q10 (CoQ10), emulsifier-free
emulsions were developed with a new emulsification process using high-frequency
ultrasound (HFU) at 1.7MHz. Nano-emulsions containing CoQ10 were prepared with or
without rapeseed lecithin as an emulsifier. The emulsions prepared with HFU were
compared with an emulsion of CoQ10 containing emulsifier prepared with the same
emulsification technique as well as with emulsions prepared with low-frequency
ultrasound coupled with high-pressure homogenization (LFU+HPH). The physico
chemical properties of the emulsions were determined by average droplet size
measurement with nano-droplet tracking analysis, droplet surface charge with zeta
potential measurement, surface tension and rheological behaviour. Emulsions made
by LFU+HPH with an emulsifier showed lower droplet sizes due to cavitation
generated by the HFU process. Surface tension results showed that there was no
significant difference between emulsions containing lecithin emulsifier
regardless of the preparation process or the inclusion of CoQ10. In vitro
biocompatibility tests were performed on human mesenchymal stem cells in order to
show the cytotoxicity of various formulations and the efficiency of CoQ10-loaded
emulsions. In vitro tests proved that the vectors were not toxic. Furthermore,
CoQ10 facilitated a high rate of cell proliferation and metabolic activity
especially when in an emulsifier-free formulation.
PMID- 27497934
TI - Cholecystokinin-33, but not cholecystokinin-8 shows gastrointestinal site
specificity in regulating feeding behaviors in male rats.
AB - Two separate experiments were performed to localize the gastrointestinal sites of
action regulating meal size (MS), intermeal interval (IMI) length and satiety
ratio (SR, IMI/MS) by cholecystokinin (CCK) 8 and 33. Experiment 1: CCK-8 (0,
0.05, 0.15, 0.25nmol/kg) was infused in the celiac artery (CA, supplies stomach
and upper duodenum) or the cranial mesenteric artery (CMA, supplies small and
part of the large intestine) prior to the onset of the dark cycle in free
feeding, male Sprague Dawley rats and MS (normal rat chow), IMI and SR were
recorded. Experiment 2: CCK-33 (0, 0.05, 0.15, 0.25nmol/kg) were infused in the
CA or the CMA, under the same experimental conditions above, and MS, IMI and SR
were recorded. Experiment 1 found that CCK-8 reduces MS, prolongs the IMI and
increases the SR at sites supplied by both arteries. Experiment 2 found that CCK
33 reduces MS and increases the SR at sites supplied by the CMA. We conclude that
in male rats the feeding behaviors evoked by CCK-33, but not CCK-8, are regulated
at specific gastrointestinal sites of action.
PMID- 27497936
TI - Post-operative medical and surgical complications after primary total joint
arthroplasty in solid organ transplant recipients: a case series.
AB - PURPOSE: In a series of solid organ transplant (SOT) recipients who underwent a
subsequent primary total joint arthroplasty (TJA) procedure, this study aimed to
determine: (1) 90-day morbidity and mortality after primary total knee or hip
arthroplasty (TKA and THA), (2) overall post-operative infection rates, and (3)
how complication and infection rates compared across primary TJA procedure and
type of transplant organ. METHODS: The University of Michigan Health System
database was retrospectively searched using current procedural terminology codes
for any primary TKA or THA performed at the institution in years 2000-2012 in a
patient who previously received a successful SOT at any hospital. RESULTS: The
search yielded 44 arthroplasties performed in 29 SOT recipients (average age 54.8
years, average follow-up about 30 months for both groups). No deaths were
reported, but 13/27 (48.1%) THA patients and 2/6 (33.3%) TKA patients experienced
a total of 29 complications within 90 days of surgery. One patient (3.7%) [1/27
patients, 1/37 joints] underwent revision hip arthroplasty to correct limb
length. One THA patient and two TKA patients developed infection requiring
revision surgery (3.7% and 33%, respectively). Type of transplant did not affect
complication rates (P=0.65), and infection was more common after TKA (P=0.01).
CONCLUSIONS: A series of SOT recipients demonstrated increased rates of infection
and other complications following TJA. Surgical and medical teams should work
closely to optimize this population for TJA surgery and minimize peri-operative
complications. LEVEL OF EVIDENCE & STUDY DESIGN: Level IV, Prognostic Case
Series.
PMID- 27497937
TI - Challenges in epilepsy-associated tumors.
PMID- 27497935
TI - Effort-related motivational effects of the pro-inflammatory cytokine interleukin
6: pharmacological and neurochemical characterization.
AB - RATIONALE: Motivational dysfunctions such as anergia, fatigue, and reduced effort
expenditure are common in patients with depression and other disorders. Pro
inflammatory cytokines are implicated in depression, and cytokine administration
induces motivational deficits in humans. OBJECTIVES: These studies focused on the
effects of the cytokine interleukin-6 (IL-6) on effort-related decision-making.
METHODS: Rats were assessed using the concurrent fixed ratio 5-lever
pressing/chow feeding choice procedure, which measures the tendency of rats to
work for a preferred food (high carbohydrate pellets) in the presence of a
concurrently available but less preferred substitute (lab chow). RESULTS: IL-6
(2.0-8.0 MUg/kg IP) shifted choice behavior, significantly decreasing lever
pressing and increasing chow intake. Further experiments showed that the
adenosine A2A antagonist MSX-3 and the stimulant methylphenidate attenuated the
effort-related impairments produced by IL-6, increasing lever pressing and
decreasing chow intake in IL-6 treated rats. The same doses of IL-6 did not alter
food intake or preference in parallel free-feeding choice studies, demonstrating
that these low doses were not altering preference for the high carbohydrate
pellets or generally suppressing appetite. Also, IL-6 did not affect body
temperature. Microdialysis studies showed that 8.0 MUg/kg IL-6 significantly
decreased extracellular dopamine in nucleus accumbens core. CONCLUSIONS: In
summary, IL-6 reduces the tendency to work for food, even at low doses that do
not produce fever or loss of appetite. Dopaminergic mechanisms may be involved in
these effort-related effects. This research has implications for the involvement
of cytokines in motivational dysfunctions such as anergia and fatigue.
PMID- 27497938
TI - Pathological rupture of the normal spleen: Review with the literature.
AB - INTRODUCTION: Atraumatic spontaneous rupture of the spleen is an uncommon but
fatal condition that may coexist with other disease. Our case was presented with
obvious CT findings of a spontaneous rupture of the spleen. PRESENTATION OF THE
CASE: A 75-year-old woman admitted to the emergency service with abdominal pain.
Although there was no evident splenomegaly in the abdominal CT examination, the
patient was diagnosed with diffuse large B-cell lymphoma, and densities in
harmony with the free air were detected in the spleen and the abdomen.
DISCUSSION: It is clear that a healthy spleen does not rupture without marked
trauma; hence, a doctor must carefully investigate the underlying pathology.
Splenomegaly, the infiltration of the spleen and the capsule and consequently a
splenic infarct and hemorrhage were set forth as the causes of the rupture of the
spleen in lymphomas. However, our case had no splenomegaly or splenic involvement
of lymphoma in the pathological examination. Even in the absence of splenomegaly,
rupture may develop for such reasons as inflammation and embolism. Splenic
infarcts are also in the developmental mechanism. CONCLUSION: Although atraumatic
rupture of the spleen is not prevalent, it is a case which must be considered in
an acute abdominal pain as it has highly fatal outcomes without CT exam.
PMID- 27497939
TI - Effectiveness of a barbed suture in the repair of bile duct injury during
laparoscopic cholecystectomy: Report of two cases.
AB - INTRODUCTION: Bile duct injury during laparoscopic cholecystectomy occurs in rare
cases. We report two cases using barbed suture for repair in bile duct injury
during laparoscopic cholecystectomies. PRESENTATION OF CASES: The first patient
was a 73-year-old woman who underwent elective laparoscopic cholecystectomy for
cholecystolithiasis. When the gallbladder was dissected from the bed, bile
spillage was observed and an injured small bile duct was detected. The bile duct
could not be managed using a titanium clip. The second patient was an 83-year-old
woman who underwent emergent laparoscopic cholecystectomy for gallbladder
torsion. After the gallbladder was dissected from the bed, bile spillage was
observed. In both cases, a running suture, of absorbable monofilament 3-0 barbed
suture, was used to laparoscopically repair the injuries. DISCUSSION:
Laparoscopic repair of a bile duct injury is technically challenging, especially
in the gallbladder bed where suturing is very difficult because of the tangential
approach and the risk of additional liver laceration. Barbed sutures have the
benefit of being knotless, thus, performing a running suture is not difficult,
even in laparoscopic procedures. Further, absorbable and monofilament threads are
generally better suited for biliary surgery, compared with non-absorbable and
braided sutures, because of the potential association of the other types of
materials with bile duct stone and stricture formation. CONCLUSION: We believe
that the V-LocTM device is an effective and appropriate option for bile duct
injuries that occur during laparoscopic cholecystectomies, particularly around
the gallbladder bed, and it is especially useful for surgeons unfamiliar with
intracorporeal knot tying.
PMID- 27497940
TI - The challenges of managing and following-up a case of short bowel in eastern
europe.
AB - INTRODUCTION: This article reflects on the plight of patients with short bowel
syndrome (SBS) in developing countries. SBS is life threatening, rare, complex
and often not considered a priority by healthcare planners in the developing
countries because of the high cost of treatment. Data was collected and analyzed
from 3 different hospitals in two different countries (Romania and Austria) from
November 2013 to February 2016 CASE PRESENTATION: The patient had an emergency
surgery for volvulus as a result of an extensive ischemic necrosis, with just
80cm of the bowel left and no ileocecal valve after enterectomy. Despite
intensive care and surgeries for anastomotic joint ischemic necrosis and
intestinal adhesion with just 70cm of the intestine left after primary
anastomosis, the patient remained in a catabolic state (metabolic acidosis,
severe malabsorption and loss of nutrients, water and electrolytes through
diarrhea) and was transferred overseas where two more surgeries (intestinal
stomas) and good intensive care helped to achieve enteral autonomy at the optimal
time. DISCUSSION: This immune-deficient patient was exposed to various types of
bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa). Two years after surgery
an acute enterocolitis with salmonella infection and resultant intestinal failure
treated in patient's country of origin failed to achieve enteral nutrition
warranting a second overseas transfer. CONCLUSION: The lack of sufficient mucosal
surface followed by long time intestinal adaptation process is crucial in
determining bowel functional capacity. Long time hospital stay and cost was
reduced through a parental home healthcare management training scheme.
PMID- 27497941
TI - Bowel obstruction and perforation due to a large gallstone. A case report.
AB - INTRODUCTION: Gallstone bowel obstruction is a rare form of mechanical ileus
usually presenting in elderly patients, and is associated with chronic or acute
cholecystitis episodes. CASE PRESENTATION: We present the case of an 80year old
female with abdominal pain, inability to defecate and recurrent episodes of
diarrhea for the past 8 months. CT examination uncovered a cholecystoduodenal
fistula along with gas in the gall bladder and the presence of a >=2cm gallstone
inside the small bowel lumen causing obstruction. Patient was admitted to the
operating room, where a 3.2cm gallstone was located in the terminal ileus. A
rupture was found in the antimesenteric part of a discolored small bowel segment,
approximately 60cm from the ileocaecal valve, through which the gallstone was
recovered. The bowel regained its peristalsis, and the rupture was debrided and
sutured. Patient was discharged uneventfully on the 6th postoperative day.
DISCUSSION: Gallstone ileus is caused due to the impaction of a gallstone inside
the bowel lumen. It usually passes through a fistula connecting the gallstone
with the gastrointestinal tract. It can present with nonspecific or acute
abdominal symptoms. CT usually confirms the diagnosis, while there are a number
of treatment options; conservative, minimal invasive and surgical. Our patient
was successfully relieved of the obstruction through recovery of the gallstone
using open surgery, with no repair of the fistula. CONCLUSSION: Although rare,
gallstones must be suspected as a possible cause of bowel obstruction, especially
in elderly patients reporting biliary symptoms.
PMID- 27497942
TI - Difficult diagnosis of hemoperitoneum in a patient with a pelvic mass of large
size.
AB - INTRODUCTION: Intraperitoneal hemorrhage caused by a uterine myoma is rare
(Tajima et al., 2015). PRESENTATION OF CASE: A 47-year-old woman was admitted to
the emergency room for worsening abdominal pain. Ultrasound revealed fluid filled
almost the entire abdominal cavity as well as the presence of a mass of about
20cm near the uterus. It was not easy to understand the nature of the fluid by
ultrasound. It appeared to be ascites with a tumoral pelvic neoformation. On TC
there was extravasation of contrast material, but the bleeding site was not
identifiable. An emergency operation was performed. Bleeding was from a
subserosalmyoma on the anterior wall of the uterus; myoma measured approximately
20cm in maximum diameter. Pathological assessment of the resected specimen
revealed bleeding from ruptured tortuous veins on a serosal-type uterine myoma.
DISCUSSION: Spontaneous rupture of a vein or an artery overlying a myoma has been
documented in English literature on the subject, although it is extremely rare
(Tajima et al., 2015). CONCLUSION: The differential diagnosis between ascites and
hemoperitoneum is sometimes not easy. Ultrasound is a helpful instrument in
expert hands to make a diagnosis of hemoperitoneum. The aid of other diagnostic
methods as TC help the clinician to arrive at the correct diagnosis quickly.
PMID- 27497943
TI - Mesenchymal stem cells enhance alpha-synuclein clearance via M2 microglia
polarization in experimental and human parkinsonian disorder.
AB - Microglia in the brain show distinctive phenotypes that serve different
functions. In particular, M2-polarized microglia are anti-inflammatory and
phagocytic cells that serve a restorative function. In this study, we
investigated whether mesenchymal stem cells (MSCs) enhance the phagocytic
clearance of alpha-synuclein via M2 microglia polarization, and thereby exert
neuroprotective effects in alpha-synuclein-enriched experimental models and
patients with multiple system atrophy (MSA). Treatment of BV2 cells with alpha
synuclein induced an inflammatory phenotype, whereas co-culture of alpha
synuclein-treated BV2 cells with MSCs induced an anti-inflammatory M2 phenotype,
with decreased alpha-synuclein levels and increased lysosomal activity, leading
to greater viability of neuronal cells co-cultured with BV2 cells. Using IL-4
receptor siRNA in BV2 cells and IL-4 siRNA in MSCs, we found that M2 microglia
polarization was induced by IL-4 secreted from MSCs. In alpha-synuclein
inoculated mice, MSC treatment induced M2 microglia polarization decreased alpha
synuclein levels, and had a prosurvival effect on neurons. Using IL-4 and IL-4
receptor knockout mice, we further confirmed that IL-4 secreted from MSCs induced
phagocytic clearance of alpha-synuclein through M2 microglia polarization. Next,
we found that the cerebrospinal fluid (CSF) from MSC-transplanted MSA patients
induced microglia M2 polarization and had a prosurvival effect via enhanced
clearance of alpha-synuclein in alpha-synuclein-treated BV2 cells. Finally, a
serial CSF study demonstrated that changes in oligomeric alpha-synuclein from
baseline to 1-year follow-up were greater in the CSF of MSC-transplanted MSA
patients than in placebo-transplanted MSA patients. These findings indicate that
MSCs exert a neuroprotective effect via the clearance of extracellular alpha
synuclein by controlling microglia M2 polarization, suggesting that MSCs could be
used as a disease-modifying therapy for patients with alpha-synucleinopathies.
PMID- 27497944
TI - Fully quantitative description of hybrid TiO2 nanoparticles by means of solid
state (31)P NMR.
AB - For the first time, an absolute quantification of hybrid materials obtained from
the reaction of phenylphosphonic acid (PPA) with TiO2 nanoparticles under
different reaction conditions is reported. Next to the amount of PPA involved in
grafting to the TiO2 nanoparticles, also the PPA included in
titaniumphenylphosphonate crystallites is described quantitatively. The
quantitative analysis is based on solid state (31)P MAS NMR and is further
applied to evaluate the stability of the resulting hybrid materials towards
hydrolysis and organic solvent exposure.
PMID- 27497946
TI - Sports hernia repair with adductor tenotomy.
AB - PURPOSE: Sports hernias, or athletic pubalgia, is common in athletes, and
primarily involves injury to the fascia, muscles, and tendons of the inguinal
region near their insertion onto the pubic bone. However, management varies
widely, and rectus and adductor tenotomies have not been adequately described.
The purpose of this manuscript is to demonstrate a suture repair and a rectus and
adductor longus tenotomy technique for sports hernias. METHODS: After magnetic
resonance-imaging confirmation of sports hernias with rectus and adductor
tendonitis, 22 patients underwent a suture herniorrhaphy with adductor tenotomy.
The procedure is performed through a 4-cm incision, and a fascial release of the
rectus abdominis and adductor tenotomy is performed to relieve the opposing
vector forces on the pubic bone. RESULTS: All 22 patients returned to their
respective sports and regained their ability to perform at a high level,
including professional status. No further surgery was required. CONCLUSION: In
athletes with MRI confirmation of rectus and adductor longus injuries, tenotomies
along with a herniorraphy may improve outcomes. A suture repair to reinforce the
inguinal floor prevents mesh-related complications, especially in young athletes.
PMID- 27497947
TI - A rare case of intervertebral internal hernia.
PMID- 27497948
TI - Principles of ipsilateral and contralateral cortico-cortical connectivity in the
mouse.
AB - Structural connectivity among cortical areas provides the substrate for
information exchange in the cerebral cortex and is characterized by systematic
patterns of presence or absence of connections. What principles govern this
cortical wiring diagram? Here, we investigate the relation of physical distance
and cytoarchitecture with the connectional architecture of the mouse cortex.
Moreover, we examine the relation between patterns of ipsilateral and
contralateral connections. Our analysis reveals a mirrored and attenuated
organization of contralateral connections when compared with ipsilateral
connections. Both physical distance and cytoarchitectonic similarity of cortical
areas are related to the presence or absence of connections. Notably, our
analysis demonstrates that the combination of these factors relates better to
cortico-cortical connectivity than each factor in isolation and that the two
factors relate differently to ipsilateral and contralateral connectivity.
Physical distance is more tightly related to the presence or absence of
ipsilateral connections, but its relevance greatly diminishes for contralateral
connections, while the contribution of cytoarchitectonic similarity remains
relatively stable. Our results, together with similar findings in the cat and
macaque cortex, suggest that a common set of principles underlies the macroscale
wiring of the mammalian cerebral cortex.
PMID- 27497949
TI - Elevated plasma heparin-binding protein is associated with early death after
resuscitation from cardiac arrest.
AB - BACKGROUND: An intense systemic inflammatory response is observed following
reperfusion after cardiac arrest. Heparin-binding protein (HBP) is a granule
protein released by neutrophils that intervenes in endothelial permeability
regulation. In the present study, we investigated plasma levels of HBP in a large
population of patients resuscitated from out-of-hospital cardiac arrest. We
hypothesized that high circulating levels of HBP are associated with severity of
post-cardiac arrest syndrome and poor outcome. METHODS: Plasma was obtained from
278 patients enrolled in a prospective multicenter observational study in 21
intensive care units (ICU) in Finland. HBP was assayed at ICU admission and 48 h
later. Multiple organ dysfunction syndrome (MODS) was defined as the 24 h
Sequential Organ Failure Assessment (SOFA) score >= 12. ICU death and 12-month
Cerebral Performance Category (CPC) were evaluated. Multiple linear and logistic
regression tests and receiver operating characteristic curves with area under the
curve (AUC) were performed. RESULTS: Eighty-two percent of patients (229 of 278)
survived to ICU discharge and 48 % (133 of 276) to 1 year with a favorable
neurological outcome (CPC 1 or 2). At ICU admission, median plasma levels of HBP
were markedly elevated, 15.4 [9.6-31.3] ng/mL, and persisted high 48 h later,
14.8 [9.8-31.1] ng/mL. Admission levels of HBP were higher in patients who had
higher 24 h SOFA and cardiovascular SOFA score (p < 0.0001) and in those who
developed MODS compared to those who did not (29.3 [13.7-60.1] ng/mL vs. 13.6
[9.1-26.2] ng/mL, p < 0.0001; AUC = 0.70 +/- 0.04, p = 0.0001). Admission levels
of HBP were also higher in patients who died in ICU (31.0 [17.7-78.2] ng/mL)
compared to those who survived (13.5 [9.1-25.5] ng/mL, p < 0.0001) and in those
with an unfavorable 12-month neurological outcome compared to those with a
favorable one (18.9 [11.3-44.3] ng/mL vs. 12.8 [8.6-30.4] ng/mL, p < 0.0001).
Admission levels of HBP predicted early ICU death with an AUC of 0.74 +/- 0.04 (p
< 0.0001) and were independently associated with ICU death (OR [95 %CI] 1.607
[1.076-2.399], p = 0.020), but not with unfavorable 12-month neurological outcome
(OR [95 %CI] 1.154 [0.834-1.596], p = 0.387). CONCLUSIONS: Elevated plasma levels
of HBP at ICU admission were independently associated with early death in ICU.
PMID- 27497950
TI - Predictors of hospital readmission 1 year after ischemic stroke.
AB - Predictors of short-term readmission after ischemic stroke have been previously
identified, but few studies analyzed predictors of long-term readmission, namely
early imaging findings and treatment with intravenous thrombolysis (IVT). To
characterize predictors of hospital readmission during the first year after
hospitalization for ischemic stroke. The study consists of a retrospective cohort
of consecutive ischemic stroke patients admitted in a Portuguese university
hospital during 2013, who survived index hospitalization. We collected clinical
and imaging information using the electronical clinical record. Information
concerning 1-year unplanned hospital readmissions was assessed using the
Portuguese electronic Health Data Platform. Descriptive and univariate analyses,
Kaplan-Meier survival curve and multivariate survival analysis with Cox
regression model were used. We included 480 patients, 50.6 % women, median age 79
years (interquartile range = 68-85). One-year hospital readmissions occurred in
165 patients [34.4 %, 95 % confidence interval (95 % CI) 30.2-38.7]. The main
causes for readmission were infectious diseases (43.8 %), ischemic stroke or
transient ischemic attack recurrence (13.2 %) and cardiac diseases (6.4 %). In
hospital mortality associated with readmission was 23.0 %. The independent
predictors of 1-year hospital readmission after ischemic stroke were admission
mini-National Institute of Health Stoke Scale [hazards ratio (HR) 1.05, 95 % CI
1.02-1.08, p = 0.002], and mild or absent early signs of ischemia on admission
computed tomography (CT) (HR 0.54, 95 % CI 0.32-0.91, p = 0.021) and IVT (HR
0.11, 95 % CI 0.01-0.80, p = 0.029). Hospital readmission during the first year
after ischemic stroke occurs in 1/3 of patients and is associated with high in
hospital mortality. Clinical stroke severity, early signs of ischemia on
admission CT, and treatment with IVT are independent predictors of 1-year
hospital readmission.
PMID- 27497945
TI - Mitochondrial Ca2+ and regulation of the permeability transition pore.
AB - The mitochondrial permeability transition pore was originally described in the
1970's as a Ca2+ activated pore and has since been attributed to the pathogenesis
of many diseases. Here we evaluate how each of the current models of the pore
complex fit to what is known about how Ca2+ regulates the pore, and any insight
that provides into the molecular identity of the pore complex. We also discuss
the central role of Ca2+ in modulating the pore's open probability by directly
regulating processes, such as ATP/ADP balance through the tricarboxylic acid
cycle, electron transport chain, and mitochondrial membrane potential. We review
how Ca2+ influences second messengers such as reactive oxygen/nitrogen species
production and polyphosphate formation. We discuss the evidence for how Ca2+
regulates post-translational modification of cyclophilin D including
phosphorylation by glycogen synthase kinase 3 beta, deacetylation by sirtuins,
and oxidation/ nitrosylation of key residues. Lastly we introduce a novel view
into how Ca2+ activated proteolysis through calpains in the mitochondria may be a
driver of sustained pore opening during pathologies such as ischemia reperfusion
injury.
PMID- 27497951
TI - Zika, dengue, and chikungunya co-infection in a pregnant woman from Colombia.
AB - The clinical findings of a pregnant woman from Colombia with a triple co
infection caused by dengue, chikungunya, and Zika viruses are described. Weekly
obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains
under follow-up and management according to the standard guidelines for the
management of Zika virus-infected pregnant women.
PMID- 27497952
TI - Colistin resistance - is this pushing us over the edge into the abyss of pan
resistance?
PMID- 27497953
TI - Down-Regulation of MicroRNA-137 Improves High Glucose-Induced Oxidative Stress
Injury in Human Umbilical Vein Endothelial Cells by Up-Regulation of AMPKalpha1.
AB - BACKGROUND/AIMS: To investigate the effects of miR-137 on high glucose (HG)
induced vascular injury, and to establish the mechanism underlying these effects.
METHODS: Human umbilical vein endothelial cells (HUVECs) were transfected with
miR-137 inhibitor or mimic, and then treated with normal or high glucose. Cell
viability and apoptosis were detected by using the Cell Counting Kit-8 (CCK-8)
assay and flow cytometry, respectively. Reactive oxygen species (ROS),
malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by
fluorescent probe (DCFH-DA), thiobarbituric acid reaction, and the nitroblue
tetrazolium assay, respectively. The mRNA and protein expressions of AMPKalpha1
were determined by qRT-PCR and Western blotting. RESULTS: Down-regulation of miR
137 dramatically reverted HG-induced decreases in cell viability and SOD levels
and increases in apoptosis, ROS and MDA levels. Moreover, bioinformatics analysis
predicted that the AMPKalpha1 was a potential target gene of miR-137. Luciferase
reporter assay demonstrated that miR-137 could directly target AMPKalpha1.
AMPKalpha1 overexpression had the similar effect as miR-137 inhibition. Down
regulation of AMPKalpha1 in HUVECs transfected with miR-137 inhibitor partially
reversed the protective effect of miR-137 inhibition on HG-induced oxidative
stress in HUVECs. CONCLUSION: Down-regulation of miR-137 ameliorates HG-induced
injury in HUVECs by overexpression of AMPKalpha1, leading to increasing cellular
reductive reactions and decreasing oxidative stress. These results provide
further evidence for protective effect of miR-137 inhibition on HG-induced
vascular injury.
PMID- 27497954
TI - State of inequality in diphtheria-tetanus-pertussis immunisation coverage in low
income and middle-income countries: a multicountry study of household health
surveys.
AB - BACKGROUND: Immunisation programmes have made substantial contributions to
lowering the burden of disease in children, but there is a growing need to ensure
that programmes are equity-oriented. We aimed to provide a detailed update about
the state of between-country inequality and within-country economic-related
inequality in the delivery of three doses of the combined diphtheria, tetanus
toxoid, and pertussis-containing vaccine (DTP3), with a special focus on
inequalities in high-priority countries. METHODS: We used data from the latest
available Demographic and Health Surveys and Multiple Indicator Cluster Surveys
done in 51 low-income and middle-income countries. Data for DTP3 coverage were
disaggregated by wealth quintile, and inequality was calculated as difference and
ratio measures based on coverage in richest (quintile 5) and poorest (quintile 1)
household wealth quintiles. Excess change was calculated for 21 countries with
data available at two timepoints spanning a 10 year period. Further analyses were
done for six high-priority countries-ie, those with low national immunisation
coverage and/or high absolute numbers of unvaccinated children. Significance was
determined using 95% CIs. FINDINGS: National DTP3 immunisation coverage across
the 51 study countries ranged from 32% in Central African Republic to 98% in
Jordan. Within countries, the gap in DTP3 immunisation coverage suggested pro
rich inequality, with a difference of 20 percentage points or more between
quintiles 1 and 5 for 20 of 51 countries. In Nigeria, Pakistan, Laos, Cameroon,
and Central African Republic, the difference between quintiles 1 and 5 exceeded
40 percentage points. In 15 of 21 study countries, an increase over time in
national coverage of DTP3 immunisation was realised alongside faster improvements
in the poorest quintile than the richest. For example, in Burkina Faso, Cambodia,
Gabon, Mali, and Nepal, the absolute increase in coverage was at least 2.0
percentage points per year, with faster improvement in the poorest quintile.
Substantial economic-related inequality in DTP3 immunisation coverage was
reported in five high-priority study countries (DR Congo, Ethiopia, Indonesia,
Nigeria, and Pakistan), but not Uganda. INTERPRETATION: Overall, within-country
inequalities in DTP3 immunisation persist, but seem to have narrowed over the
past 10 years. Monitoring economic-related inequalities in immunisation coverage
is warranted to reveal where gaps exist and inform appropriate approaches to
reach disadvantaged populations. FUNDING: None.
PMID- 27497955
TI - Trends in immunisation inequity: evidence, rights, and planning.
PMID- 27497957
TI - Hanging Maneuver for Stomach Traction in Laparoscopic Distal Pancreatic
Resections: An Original Technique Applied in 218 Patients.
AB - BACKGROUND: Stomach traction done to expose the pancreas is still a problem in
laparoscopic left pancreatic resections. We developed a simple hanging maneuver
to retract the stomach rapidly and effectively. METHODS: After dividing the
gastrocolic ligament, the stomach was encircled with a tape, turned along its
horizontal axis and pulled with an epigastric trocar, which was later removed.
This technique was used in all patients who underwent laparoscopic left
pancreatic resections including 165 distal pancreatectomies (DP), 35 central
pancreatectomies (CP) and 18 enucleations (En). Demographics, surgical and
postoperative outcome data were recorded. RESULTS: There were no mortalities. The
mean operative time for DP, CP and En were 174, 191 and 104 min, respectively.
The transfusion (0-4%) and conversion (0-3%) rates were low for all procedures.
Morbidity was mainly represented by pancreatic fistula and grades (B + C) for DP,
CP and En were observed in 26, 22 and 17%, respectively. No complication related
to hanging of the stomach, like gastric perforation, was observed. Re
intervention and the mean hospital stay for DP, CP and En were observed in 5, 11
and 0% and were 16, 22 and 12, respectively. The readmission rate was low (0-9%).
CONCLUSIONS: Hanging maneuver of the stomach is a simple procedure to rapidly,
safely and effectively retract the stomach during left laparoscopic pancreatic
resections.
PMID- 27497959
TI - Postnatal Mother-to-Infant Attachment in Subclinically Depressed Mothers: Dyads
at Risk?
AB - BACKGROUND: Dyadic interactions between children and depressed mothers have been
characterized as less synchronous and with lower maternal sensitivity, fostering
an inharmonious, insecure attachment relationship between mother and child. Thus,
these children may experience enhanced early life stress and are at higher risk
of disturbed socioemotional development. Recently, this association has also been
found in women with mild depressive symptoms. However, potential confounding
effects of mother's history of own rearing experiences or infant temperament on
the link between depressive symptoms and postnatal mother-to-infant attachment
have not yet been investigated. METHODS: Differences in mother-to-infant
attachment (e.g. quality of attachment, absence of hostility, and pleasure in
interaction) between mothers with and without symptoms of depression 6-8 months
postpartum were analyzed in a low-risk community sample (n = 38, 19 per group).
Depressive symptomatology was measured with the Beck Depression Inventory (BDI
II) and the Edinburgh Postnatal Depression Scale (EPDS). Depressed mothers
indicated mild-to-moderate depressive symptomatology (mean BDI-II 11.26 +/- 3.86)
but did not fulfill criteria for a major depressive episode and, thus, were
referred to as 'subclinically' depressed. Potential confounders, namely maternal
history of own rearing experiences and infant temperament, were explored by
multivariate AN(C)OVA. RESULTS: Primiparous mothers with subclinical depression
differed significantly from healthy control mothers, i.e. showed poorer mother-to
infant attachment and higher infant-related hostility 6-8 months postpartum. As
expected, infant temperament and mother's history of own rearing experiences were
both associated with mother-to-infant attachment but did not explain the negative
effects of subclinical depression on the mother-infant relationship. CONCLUSIONS:
Given the high prevalence of maternal depression, the current findings give
reason for increased concern for the developing mother-child relationship.
Therefore, early interventions are needed that focus on the mother-child dyad and
target not only clinically but also subclinically depressed mothers.
PMID- 27497958
TI - Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and
lysosomal function.
AB - : Cumulative evidence suggests the importance of organelle homeostasis in
regulating metabolic functions in response to various cellular stresses.
Particularly, the dynamism and health of the mitochondria-peroxisome network
through fission and fusion are essential for cellular function; dysfunctional
dynamism underlies the pathogenesis of several degenerative diseases including
Parkinson's disease. Here, we investigated the role of Fis1 in cartilage
homeostasis and its relevance to osteoarthritis (OA). We found that Fis1 is
significantly suppressed in human OA chondrocytes compared to that in normal
chondrocytes. Fis1 depletion through siRNA induced peroxisomal dysfunction.
Moreover, Fis1 suppression altered miRNA profiles, especially those implicated in
lysosomal regulation. Lysosomal destruction using LAMP-1-specific targeted
nanorods or lysosomal dysfunction through chloroquine treatment resulted in
enhanced chondrocyte apoptosis and/or suppression of autophagy. Accordingly,
lysosomal activity and autophagy were severely decreased in OA chondrocytes
despite abundant LAMP-1-positive organelles. Moreover, Fis1 morpholino-injected
zebrafish embryos displayed lysosome accumulation, mitochondrial dysfunction, and
peroxisome reduction. Collectively, these data suggest interconnected links among
Fis1-modulated miRNA, lysosomes, and autophagy, which contributes to chondrocyte
survival/apoptosis. This study represents the first functional study of Fis1 with
its pathological relevance to OA. Our data suggest a new target for controlling
cartilage-degenerative diseases, such as OA. KEY MESSAGE: Fis1 suppression in OA
chondrocytes induces accumulation and inhibition of lysosomes. Fis1 suppression
alters miRNAs, especially those implicated in lysosomal regulation. Lysosomal
destruction results in chondrocyte apoptosis and suppression of autophagy. Fis1
depletion in zebrafish causes lysosome accumulation, mitochondrial dysfunction,
and peroxisome reduction. This is the first functional study of Fis1 and its
pathological relevance to OA.
PMID- 27497960
TI - Sorption kinetics of zinc and nickel on modified chitosan.
AB - This study was conducted to evaluate the effect of equilibration time on
adsorption of zinc [Zn(II)] and nickel [Ni(II)] on pure and modified chitosan
beads. The initial adsorption of Zn(II) was high on molybdenum (Mo)-impregnated
chitosan beads (MoCB) during the initial 60 min. However, after 240 min, Zn(II)
adsorption occurred more on single super phosphate chitosan beads (SSPCB),
followed by monocalcium phosphate chitosan beads (MCPCB), untreated pure chitosan
beads (UCB), and MoCB. Similarly, Ni(II) adsorption was greatest on MoCB during
the initial 60 min. At the conclusion of the experiment (at 240 min), the
greatest adsorption was occurred on MCPCB, followed by MoCB, UCB, and SSPCB.
Chemical sorption and intra-particle diffusion were probably the dominant
processes responsible for Zn(II) and Ni(II) sorption onto chitosan beads. The
results demonstrated that modified chitosan beads were effective in adsorbing Zn
and Ni and hence, could be used for the removal of these toxic metals from soil.
PMID- 27497961
TI - Polycyclic aromatic hydrocarbons in three commercially available fish species
from the Bonny and Cross River estuaries in the Niger Delta, Nigeria.
AB - The concentrations and compositional patterns of the USEPA 16 polycyclic aromatic
hydrocarbons were investigated in three commercially available fish species,
Chrysichthys nigrodigitatus, Cynoglossus senegalensis and Polydactylus
quadratifilis, from the Bonny and Cross River systems in the eastern Niger Delta
of Nigeria. The objective of the study was to provide useful information on the
levels and sources of polycyclic aromatic hydrocarbons (PAHs) and the associated
risks with their consumption. The 16 PAHs in the fish samples were extracted by
ultrasonication with hexane/dichloromethane, and the concentrations of PAHs in
the extracts were quantified by gas chromatography-mass spectrometry. The
measured concentrations of the ?16 PAHs in Chrysichthys nigrodigitatus,
Polydactylus quadratifilis and Cynoglossus senegalensis ranged from 106 to 491,
from 43.1 to 1734 and from 96.4 to 937 MUg kg(-1) in the Bonny River system and
from 20.0 to 975, from 24.7 to 506 and from 24.9 to 387 MUg kg(-1) in the Cross
River system, respectively. The compositional patterns of the PAHs showed that
the three- and four-ringed PAHs were the major contributors to the PAH burden in
these fish species. The diagnostic ratios indicate that the PAHs in these fish
samples originated mainly from combustion processes. The health risk assessment,
as determined from the benzo[a]pyrene potency equivalent factor, margin of
exposure and incremental lifetime cancer risk, indicates that PAHs in the
majority of these fish species can induce potential carcinogenic effects.
PMID- 27497962
TI - Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart
and a Possible Molecular Mechanism.
AB - BACKGROUND/AIMS: Extensive research has explored the role of aldosterone in
insulin resistance. Recent evidence suggests that the mineralocorticoid receptor
(MR) mediates aldosterone-induced dysregulation of cytokines, and most of this
research has focused on adjustments in fat tissue and adipocytes. However, the
direct effect of MR blockade on insulin resistance in cardiomyocytes remains
largely unknown. In the present study, we investigated whether MR blockade
improves insulin-sensitizing factors in insulin-resistant rats and attenuates the
dysregulation of the aldosterone-related transport of adiponectin and glucose in
cardiomyocytes and examined the underlying mechanisms. METHODS: The effects of
aldosterone, MR inhibitors (e.g., eplerenone), a peroxisome proliferator
activated receptor (PPAR) alpha agonist, and a p38 mitogen-activated protein
kinase (MAPK) inhibitor on adiponectin and glucose transport were studied at the
mRNA and protein levels in vitro and in vivo. RESULTS: Our data revealed that
aldosterone reduced the expression of adiponectin and inhibited the transport of
glucose in cardiomyocytes and that MR blockade reversed these affects. In vivo,
MR blockade improved insulin-sensitive parameters and increased adiponectin
expression in the myocardia of high-fat diet rats. Furthermore, aldosterone
promoted p38MAPK expression but negatively affected PPARalpha expression, and the
downregulation of adiponectin by aldosterone was reversed by MR blockade, a
PPARalpha agonist, and a p38 MAPK inhibitor. CONCLUSION: The above results
suggested that aldosterone promoted insulin resistance in the heart and that this
effect could be partly reversed by MR blockade through signal transduction in the
P38 MAPK pathway and PPARalpha.
PMID- 27497963
TI - Digital camera and smartphone as detectors in paper-based chemiluminometric
genotyping of single nucleotide polymorphisms.
AB - Chemi(bio)luminometric assays have contributed greatly to various areas of
nucleic acid analysis due to their simplicity and detectability. In this work, we
present the development of chemiluminometric genotyping methods in which (a)
detection is performed by using either a conventional digital camera (at ambient
temperature) or a smartphone and (b) a lateral flow assay configuration is
employed for even higher simplicity and suitability for point of care or field
testing. The genotyping of the C677T single nucleotide polymorphism (SNP) of
methylenetetrahydropholate reductase (MTHFR) gene is chosen as a model. The
interrogated DNA sequence is amplified by polymerase chain reaction (PCR)
followed by a primer extension reaction. The reaction products are captured
through hybridization on the sensing areas (spots) of the strip. Streptavidin
horseradish peroxidase conjugate is used as a reporter along with a
chemiluminogenic substrate. Detection of the emerging chemiluminescence from the
sensing areas of the strip is achieved by digital camera or smartphone. For this
purpose, we constructed a 3D-printed smartphone attachment that houses
inexpensive lenses and converts the smartphone into a portable chemiluminescence
imager. The device enables spatial discrimination of the two alleles of a SNP in
a single shot by imaging of the strip, thus avoiding the need of dual labeling.
The method was applied successfully to genotyping of real clinical samples.
Graphical abstract Paper-based genotyping assays using digital camera and
smartphone as detectors.
PMID- 27497964
TI - Molecularly imprinted polymer nanoparticles-based electrochemical sensor for
determination of diazinon pesticide in well water and apple fruit samples.
AB - In this research, an electrochemical sensor based on molecularly imprinted
polymer (MIP) nanoparticles for selective and sensitive determination of diazinon
(DZN) pesticides was developed. The nanoparticles of diazinon imprinted polymer
were synthesized by suspension polymerization and then used for modification of
carbon paste electrode (CPE) composition in order to prepare the sensor. Cyclic
voltammetry (CV) and square wave voltammetry (SWV) methods were applied for
electrochemical measurements. The obtained results showed that the carbon paste
electrode modified by MIP nanoparticles (nano-MIP-CP) has much higher adsorption
ability for diazinon than the CPE based non-imprinted polymer nanoparticles (nano
NIP-CP). Under optimized extraction and analysis conditions, the proposed sensor
exhibited excellent sensitivity (95.08 MUA L MUmol(-1)) for diazinon with two
linear ranges of 2.5 * 10(-9) to 1.0 * 10(-7) mol L(-1) (R (2) = 0.9971) and 1.0
* 10(-7) to 2.0 * 10(-6) mol L(-1) (R (2) = 0.9832) and also a detection limit of
7.9 * 10(-10) mol.L(-1). The sensor was successfully applied for determination of
diaznon in well water and apple fruit samples with recovery values in the range
of 92.53-100.86 %. Graphical abstract Procedure for preparation of
electrochemical sensor based on MIP nanoparticles for determination of diazinon.
PMID- 27497965
TI - Contaminant screening of wastewater with HPLC-IM-qTOF-MS and LC+LC-IM-qTOF-MS
using a CCS database.
AB - Non-target analysis has become an important tool in the field of water analysis
since a broad variety of pollutants from different sources are released to the
water cycle. For identification of compounds in such complex samples, liquid
chromatography coupled to high resolution mass spectrometry are often used. The
introduction of ion mobility spectrometry provides an additional separation
dimension and allows determining collision cross sections (CCS) of the analytes
as a further physicochemical constant supporting the identification. A CCS
database with more than 500 standard substances including drug-like compounds and
pesticides was used for CCS data base search in this work. A non-target analysis
of a wastewater sample was initially performed with high performance liquid
chromatography (HPLC) coupled to an ion mobility-quadrupole-time of flight mass
spectrometer (IM-qTOF-MS). A database search including exact mass (+/-5 ppm) and
CCS (+/-1 %) delivered 22 different compounds. Furthermore, the same sample was
analyzed with a two-dimensional LC method, called LC+LC, developed in our group
for the coupling to IM-qTOF-MS. This four dimensional separation platform
revealed 53 different compounds, identified over exact mass and CCS, in the
examined wastewater sample. It is demonstrated that the CCS database can also
help to distinguish between isobaric structures exemplified for cyclophosphamide
and ifosfamide. Graphical Abstract Scheme of sample analysis and database
screening.
PMID- 27497966
TI - Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat
cancer.
AB - The detection of cancer biomarkers freely circulating in blood offers new
opportunities for cancer early diagnosis, patient follow-up, and therapy efficacy
assessment based on liquid biopsy. In particular, circulating cell-free nucleic
acids released from tumor cells have recently attracted great attention also
because they become detectable in blood before the appearance of other
circulating biomarkers, such as circulating tumor cells. The detection of
circulating nucleic acids poses several technical challenges that arise from
their low concentration and relatively small size. Here, possibilities offered by
innovative biosensing approaches for the detection of circulating DNA in
peripheral blood and blood-derived products such as plasma and serum blood are
discussed. Different transduction principles are used to detect circulating DNAs
and great advantages are derived from the combined use of nanostructured
materials.
PMID- 27497967
TI - Quantitative aspects of microchip isotachophoresis for high precision
determination of main components in pharmaceuticals.
AB - Although microchip electrophoresis (MCE) is intended to provide reliable
quantitative data, so far there is only limited attention paid to these important
aspects. This study gives a general overview of key aspects to be followed to
reach high-precise determination using isotachophoresis (ITP) on the microchip
with conductivity detection. From the application point of view, the procedure
for the determination of acetate, a main component in the pharmaceutical
preparation buserelin acetate, was developed. Our results document that run-to
run fluctuations in the sample injection volume limit the reproducibility of
quantitation based on the external calibration. The use of a suitable internal
standard (succinate in this study) improved the repeatability of the precision of
acetate determination from six to eight times. The robustness of the procedure
was studied in terms of impact of fluctuations in various experimental parameters
(driving current, concentration of the leading ions, pH of the leading
electrolyte and buffer impurities) on the precision of the ITP determination. The
use of computer simulation programs provided means to assess the ITP experiments
using well-defined theoretical models. A long-term validity of the calibration
curves on two microchips and two MCE equipments was verified. This favors ITP
over other microchip electrophoresis techniques, when chip-to-chip or equipment
to-equipment transfer of the analytical method is required. The recovery values
in the range of 98-101 % indicate very accurate determination of acetate in
buserelin acetate, which is used in the treatment of hormone-dependent tumors.
This study showed that microchip ITP is suitable for reliable determination of
main components in pharmaceutical preparations.
PMID- 27497968
TI - Comparison of methods for wavelength combination selection from multi-wavelength
fluorescence spectra for on-line monitoring of yeast cultivations.
AB - The on-line monitoring with two-dimensional (2D) fluorescence spectroscopy of
Saccharomyces cerevisiae batch cultivations was applied to monitor glucose,
ethanol, and biomass concentrations. The measurement of one spectrum by the 2D
fluorescence spectrometer has 120 fluorescence intensity values of excitation and
emission wavelength combinations (WLCs); scattered light is not considered here.
To identify which WLCs of the multi-wavelength fluorescence spectra carry
important and relevant information regarding the analyte concentrations, three
different methods were compared: a method based on loadings, variable importance
in projection, and ant colony optimization. The five selected WLCs for a
particular analyte from each method were evaluated by multiple linear regression
models to find the most significant variable subsets for predicting the sample
concentrations. The most significant WLCs relevant to the three sample properties
contained seven different excitation and emission wavelengths, which can combine
with each other to have 38 possible wavelength combinations in the fluorescence
measurement. Partial least squares (PLS) models were calibrated with the 38
possible variables and the off-line data for the prediction of glucose, ethanol,
and biomass concentrations. The best prediction from the PLS models had the
percentage of root mean square error of prediction (pRMSEP) in the range of 3.1
6.3 %, which was similar to pRMSEPs of the PLS models with the full variables.
Based on these results, it is promising to build up a specific inexpensive
fluorescence sensor for the yeast cultivation process using light-emitting diodes
and photodiodes. Graphical abstract Flow chart of the selection of important and
relevant WLCs by the three methods to predict glucose, ethanol, and biomass
concentrations.
PMID- 27497969
TI - Nano selenium as antioxidant agent in a multilayer food packaging material.
AB - Selenium nanoparticles (SeNPs) were incorporated in a flexible multilayer plastic
material using a water-base adhesive as vehicle for SeNPs. The antioxidant
performance of the original solutions containing spherical SeNPs of 50-60 nm
diameter, the adhesive containing these SeNPs, and the final multilayer plastic
material to be used as food packaging were quantitatively measured. The radical
scavenging capacity due to SeNPs was quantified by a free radical assay developed
in the laboratory and by the diphenyl-1-picrylhydrazyl (DPPH) method. DPPH was
not efficient to measure the scavenging capacity in the multilayer when the free
radical scavenger is not in the surface in contact with it. Several multilayer
laminated structures composed by [PET (20 m)-adhesive-LDPE (with variable
thickness from 35 to 90 MUm)] were prepared and measured, demonstrating for the
first time that free radicals derived from oxygen (OH., O2., and O2H) cross the
PE layer and arrive at the adhesive. SeNPs remain as such after manufacture and
the final laminate is stable after 3 months of storage. The antioxidant
multilayer is a non-migrating efficient free radical scavenger, able to protect
the packaged product versus oxidation and extending the shelf life without being
in direct contact with the product. Migration tests of both Se and SeNPs to
simulants and hazelnuts demonstrated the non-migrating performance of this new
active packaging. Graphical abstract ?.
PMID- 27497970
TI - "Micromegaly": an update on the prevalence of acromegaly with apparently normal
GH secretion in the modern era.
AB - PURPOSE: Approximately 25 % of cases of clinically active acromegaly cases
treated in our academic center between 1996 and 2000, were diagnosed in patients
who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH
levels. The current study served to update the data for patients with acromegaly
referred to our facility, after increasing awareness of this "normal" GH
subpopulation throughout the medical community. METHODS: A retrospective chart
review was conducted on 157 patients with acromegaly who underwent resection of a
confirmed somatotroph pituitary adenoma at the University of Michigan Health
System between the dates of 1 Jan 2001 to 23 Sept 2015. RESULTS: Overall
prevalence of acromegalic patients with "normal" GH levels, defined as GH <4.7
ng/mL, was 31 %. Over time, the percentage of patients with "normal" GH at
diagnosis did not decline: 26 % from 2001 to 2005, 19 % from 2006 to 2010, and 47
% from 2011 to 2015. Mean pituitary tumor size was 1.8 +/- 0.1 cm for the group
with elevated GH, and 1.2 +/- 0.1 cm for the group with "normal" GH (p < 0.001).
Percent microadenomas was higher in a group with "normal" GH as compared to those
with elevated GH (48 vs. 12 %, p < 0.001), and tumors >2 cm in the maximal
diameter were encountered more frequently in the group with elevated GH (43 vs.
14 %, p < 0.001). CONCLUSIONS: Our data show that a substantial percentage of
patients with clinical acromegaly have "normal" GH, and therefore strengthens the
growing body of evidence which supports the leading role of IGF-1 levels in
diagnostic evaluation. At the present time, questions about the natural course of
"micromegaly" and treatment benefits compared to the subpopulation with elevated
GH levels remain unanswered, but research continues to build on our understanding
of the heterogeneous population of individuals.
PMID- 27497971
TI - Rituximab to treat gemcitabine-induced hemolytic-uremic syndrome (HUS) in
pancreatic adenocarcinoma: a case series and literature review.
AB - PURPOSE: Hemolytic-uremic syndrome (HUS) is a rare side effect of gemcitabine,
which is reported as having a high morbidity and mortality despite interventions
with standard HUS therapies including plasmapheresis. The purpose of this report
was to describe the successful treatment of gemcitabine-induced HUS (G-HUS) with
rituximab. It also aims to summarize the literature regarding the morbidity and
mortality of G-HUS in pancreatic adenocarcinoma depending on the treatment given,
ultimately providing some guidance for beneficial therapies. METHODS: This is a
retrospective report of three patients with pancreatic adenocarcinoma who
developed G-HUS and were treated with a combination of therapies including
rituximab. RESULTS: All three patients received a combination of therapies to
treat their HUS. One patient appeared to have some benefit with plasmapheresis.
Resolution occurred following one course of rituximab for all three patients.
This resolution has been long lasting with a minimum of eighteen month's follow
up. Similarly, in our literature review a variety of therapies were utilized, but
immune therapies appear to reverse HUS if other therapies are failing.
CONCLUSION: Rituximab can be an effective therapy for reversal of hemolysis and
stabilization of renal function in G-HUS when other therapies fail.
PMID- 27497972
TI - Introducing extra NADPH consumption ability significantly increases the
photosynthetic efficiency and biomass production of cyanobacteria.
AB - Increasing photosynthetic efficiency is crucial to increasing biomass production
to meet the growing demands for food and energy. Previous theoretical arithmetic
analysis suggests that the light reactions and dark reactions are imperfectly
coupled due to shortage of ATP supply, or accumulation of NADPH. Here we
hypothesized that solely increasing NADPH consumption might improve the coupling
of light reactions and dark reactions, thereby increasing the photosynthetic
efficiency and biomass production. To test this hypothesis, an NADPH consumption
pathway was constructed in cyanobacterium Synechocystis sp. PCC 6803. The
resulting extra NADPH-consuming mutant grew much faster and achieved a higher
biomass concentration. Analyses of photosynthesis characteristics showed the
activities of photosystem II and photosystem I and the light saturation point of
the NADPH-consuming mutant all significantly increased. Thus, we demonstrated
that introducing extra NADPH consumption ability is a promising strategy to
increase photosynthetic efficiency and to enable utilization of high-intensity
lights.
PMID- 27497973
TI - Mutation of a regulator Ask10p improves xylose isomerase activity through up
regulation of molecular chaperones in Saccharomyces cerevisiae.
AB - Economically feasible bioconversion of lignocelluloses into fuels and chemicals
is dependent on efficient utilization of all available sugars in lignocellulosic
biomass, including hextose and pentose. Previously, we constructed a xylose
fermenting strain of Saccharomyces cerevisiae through metabolic engineering and
enhanced its xylose utilization capability through evolutionary engineering.
However, the key mechanism of improved xylose utilization and xylose isomerase
activity was not identified. In this study, we applied the concept of inverse
metabolic engineering to identify the factors involved in improving xylose
utilization. Genomic sequencing of the evolved strain with fast xylose
utilization capability was performed, and mutations possibly affecting xylose
utilization were screened. Further genetic analysis of these mutant genes
revealed that mutations in ASK10 (both the site-directed mutation ASK10M475R as
well as ASK10 deletion), a stress response regulator-encoding gene, improved
growth on xylose and enhanced xylose isomerase activity. We found that mutation
of Ask10p did not increase xylose isomerase activity through interacting with the
xylose isomerase protein or through directly regulating the xylA gene
transcription. Although ASK10 deletion increased the copy number of the plasmid
and improved the transcription of xylA, the site-direct mutation ASK10M475R did
not change the plasmid copy number. Interestingly, we found that both the site
directed mutation ASK10M475R and ASK10 deletion up-regulated the transcription of
molecular chaperone-encoding genes HSP26, SSA1 and HSP104, thereby facilitating
the protein folding of xylose isomerase and enhancing xylose isomerase activity.
This study revealed the important mechanism of chaperones in xylose isomerase
activity regulation, and it provides valuable insights for efficient xylose
metabolic strain development.
PMID- 27497974
TI - Quantification of Gait Abnormalities in Healthy-Looking Multiple Sclerosis
Patients (with Expanded Disability Status Scale 0-1.5).
AB - BACKGROUND: Gait impairment is a common symptom in multiple sclerosis (MS)
patients, but there is a lack of evidence about gait performance in the group of
MS patients with no apparent disability. The aim of our study was to evaluate
gait characteristics in MS patients with no apparent impairment of walking and
with an Expanded Disability Status Scale (EDSS 0-1.5), and to determine whether
any abnormalities are detectable by common clinical tests. METHODS: This was an
observational study of 64 MS patients with an EDSS 0-1.5 and 47 age- and sex
matched healthy controls. We measured their performance in the timed 25-foot walk
test (T25FWT) and the 2-minute walk test (2MWT). The spatiotemporal parameters of
gait were measured using a GAITRite instrument. RESULTS: MS patients with no
apparent disability (EDSS 0-1.5) performed worse in T25FWT and 2MWT than normal
controls. During the self-selected walking speed test on GAITRite, MS patients
had a prolonged double support phase, and during the fast walking speed test,
they had lower cadence and decreased step length.
PMID- 27497975
TI - Thoracic Surgery in Chronic Granulomatous Disease: a 25-Year Single-Institution
Experience.
AB - INTRODUCTION: Chronic granulomatous disease (CGD) is a genetic disorder in which
phagocyte dysfunction leads to recurrent infection. Persistent pulmonary
infections sometimes require thoracic surgical intervention. We reviewed our 25
year experience to identify outcomes and prognostic factors associated with
thoracic surgery in these patients. METHODS: A retrospective single-institution
review of all patients with CGD from 1990 through 2015 was performed. Univariate
analysis identified prognostic variables to include in a Cox model. Overall
survival was estimated by the Kaplan-Meier method. RESULTS: We identified 258
patients who had 2221 admissions (both scheduled and emergent). During the period
examined, 51 thoracic operations were performed in 13.6 % (35/258) of patients
and 2.3 % (35/2221) of overall admissions. Patients undergoing surgery did not
have statistically significant differences in disease genotype compared to those
that did not require surgery. Pathogens were identified from 67 % (34/51) of
specimens. Complications occurred in 27 % (14/51), including 10 % (5/51) with
wound and 12 % (6/51) with pulmonary infections. Mortality at 30 and 90 days was
0 and 6 % (3/51), respectively. Overall survival probabilities were 75 and 62 %
at 5- and 10-year follow-up (median potential follow-up: 16.5 years),
respectively. Undergoing thoracic surgery was associated with an increased hazard
ratio for death of 3.71 (p < 0.0001). Both chest wall resection and EBL > 500 mL
were negative prognostic factors (p < 0.05). CONCLUSIONS: A minority of CGD
patients required thoracic surgery for infections refractory to antibiotic or
antifungal therapy. Patients who had these operations had significant morbidity
and relatively poor long-term survival, particularly in the cases of chest wall
resection or significant blood loss.
PMID- 27497976
TI - Ultrasound appearance of the normal Lisfranc ligament.
AB - This study aims to prospectively evaluate the ultrasound appearance of the normal
Lisfranc's ligament in 50 patients (100 ft) with no prior or current ligament
injury. Fifty normal asymptomatic patients between the ages of 18 and 80 years
were assessed. Three key features were recorded: ultrasound appearance,
thickness, and length of the Lisfranc's ligament. Patients excluded from this
study included pediatric patients and those with history of injury or symptoms
related to the foot. The mean right- and left-sided ligament (RT) thickness were
0.096 (0.021) and 0.104 (0.023), respectively. The mean right- and left-sided
ligament RT length was 0.54 (0.11) and 0.57 (0.11), respectively. The appearance
of the ligament was similar in all patients with a central thin band of
hypoechogenicity lined by hyperechoic lines on either side. Understanding the
normal appearance, thickness, and length of the Lisfranc's ligament in a large
sample is imperative to diagnose abnormal appearances of this ligament including
sprains and tears by ultrasound. Ultrasound, with its easy accessibility, can be
used in the emergency department to rapidly exclude injury of the ligament.
Increased understanding and awareness of the Lisfranc's ligament on ultrasound
can allow for more accurate diagnosis and treatment.
PMID- 27497977
TI - Using Positive Deviance to reduce medication errors in a tertiary care hospital.
AB - BACKGROUND: The number of medication errors occurring in healthcare is large and
many are preventable. To analyze medication errors and evaluate whether Positive
Deviance is effective in reducing them. METHODS: The study was divided into three
phases: (2011- Phase I, control period; 2012 - Phase II, manager intervention,
and 2013 - Phase III, frontline healthcare worker intervention). In Phases II and
III, the Positive Deviance method (PD) was used to mitigate medication errors
classified as "C" and higher according to the National Coordinating Council for
Medication Error Reporting and Prevention (NCC MERP). The errors reported were
compared across the three study phases, as well as by the location of the
hospital unit, shift, cause, consequence, and the professional associated with
the error. RESULTS: A total of 4013 reported medication errors were analyzed. The
largest number of errors occurred at the time the medications were administered,
accounting for 35.5 % of errors in Phase I; 43.1 % in Phase II, and 55.6 % in
Phase III. Nursing staff was most commonly associated with errors; 46.4 % of
errors in Phase I, 48.5 % in Phase II, and 58.7 % in Phase III. With each
intervention, a decrease was observed in the reported error rate of 0.12 (CI 95
%, 0.18 to 0.07). CONCLUSION: Positive Deviance proved to be effective, primarily
when healthcare professionals who were involved in errors participated, as was
observed in Phase III of this study.
PMID- 27497978
TI - Atypical case of central-variant posterior reversible encephalopathy syndrome.
PMID- 27497979
TI - Rapid Quantification of Low-Viscosity Acetyl-Triacylglycerols Using Electrospray
Ionization Mass Spectrometry.
AB - Acetyl-triacylglycerols (acetyl-TAG) possess an sn-3 acetate group, which confers
useful chemical and physical properties to these unusual triacylglycerols (TAG).
Current methods for quantification of acetyl-TAG are time consuming and do not
provide any information on the molecular species profile. Electrospray ionization
mass spectrometry (ESI-MS)-based methods can overcome these drawbacks. However,
the ESI-MS signal intensity for TAG depends on the aliphatic chain length and
unsaturation index of the molecule. Therefore response factors for different
molecular species need to be determined before any quantification. The effects of
the chain length and the number of double-bonds of the sn-1/2 acyl groups on the
signal intensity for the neutral loss of short chain length sn-3 groups were
quantified using a series of synthesized sn-3 specific structured TAG. The signal
intensity for the neutral loss of the sn-3 acyl group was found to negatively
correlated with the aliphatic chain length and unsaturation index of the sn-1/2
acyl groups. The signal intensity of the neutral loss of the sn-3 acyl group was
also negatively correlated with the size of that chain. Further, the position of
the group undergoing neutral loss was also important, with the signal from an sn
2 acyl group much lower than that from one located at sn-3. Response factors
obtained from these analyses were used to develop a method for the absolute
quantification of acetyl-TAG. The increased sensitivity of this ESI-MS-based
approach allowed successful quantification of acetyl-TAG in various biological
settings, including the products of in vitro enzyme activity assays.
PMID- 27497980
TI - Bioconversion of waste office paper to hydrogen using pretreated rumen fluid
inoculum.
AB - In this study, a microbial consortium from an acid-treated rumen fluid was used
to improve the yields of H2 production from paper residues in batch reactors. The
anaerobic batch reactors, which contained paper and cellulose, were operated
under three conditions: (1) 0.5 g paper/L, (2) 2 g paper/L, and (3) 4 g paper/L.
Cellulase was added to promote the hydrolysis of paper to soluble sugars. The H2
yields were 5.51, 4.65, and 3.96 mmol H2/g COD, respectively, with substrate
degradation ranging from 56 to 65.4 %. Butyric acid was the primary soluble
metabolite in the three reactors, but pronounced solventogenesis was detected in
the reactors incubated with increased paper concentrations (2.0 and 4.0 g/L). A
substantial prevalence of Clostridium acetobutylicum (99 % similarity) was
observed in the acid-treated rumen fluid, which has been recognized as an
efficient H2-producing strain in addition to ethanol and n-butanol which were
also detected in the reactors.
PMID- 27497981
TI - Bioconversion of piceid to resveratrol by selected probiotic cell extracts.
AB - Resveratrol exerts several pharmacological activities, including anti-cancer,
anti-inflammatory, cardioprotective, or antioxidant effects. However, due to its
occurrence in plants more in glycosidic form as piceid, the bioavailability and
bioactivity are limited. The enzymatic potential of probiotics for the
transformation of piceid to resveratrol was elucidated. Cell extract from
Bifidobacteria (B.) infantis, B. bifidum, Lactobacillus (L.) casei, L. plantarum,
and L. acidophilus was evaluated for their effect in this bioconversion using
high-performance liquid chromatography (HPLC) as analytical tool. Cell extract of
B. infantis showed the highest effect on the deglycosylation of piceid to
resveratrol, already after 30 min. Cell extracts of all other tested strains
showed a significant biotransformation with no further metabolization of
resveratrol. The conversion of piceid to resveratrol is of importance to increase
bioavailability and bioactivity as shown for anti-inflammation in this study.
Cell extracts from probiotics, especially from B. infantis, may be added to
piceid containing products, for achieving higher biological effects caused by the
bioactivity of resveratrol or by health promoting of the probiotics. These
findings open a new perspective of novel combination of cell extracts from
probiotics and piceid, in health-promoting pharmaceutical and food products.
PMID- 27497982
TI - Synthesis and evaluation of Cy5.5-Rit tracer for specific near-infrared
fluorescence imaging of sentinel lymph node.
AB - Sentinel lymph nodes biopsy (SLNB) is a critically important technique to
determine the metastatic status of primary breast cancer. Here we reported the
new use of a conjugate, Cy5.5-Rituximab (Cy5.5-Rit), which is specific toward the
CD20 receptor, as an imaging agent for non-invasive near-infrared fluorescence
(NIRF) imaging of sentinel lymph nodes (SLN). The conjugate, Cy5.5-Rit, was
synthesized with the ratio of dye to Rituximab close to 1.0. Both gel
electrophoresis and mass spectrometry analysis confirmed the molecular integrity
of Cy5.5-Rit. For in vivo NIRF imaging, the conjugate stayed in SLN as long as
9days post injection. The in vivo imaging results of SLN targeting were also
confirmed by in vitro HE stain. In addition, the direct fluorescence signal of
dissected lymph node demonstrated that Cy5.5-Rit binds to the surface of lymph
node cells. All of these results showed that the conjugate Cy5.5-Rit has
potential for non-invasive optical imaging of SLN.
PMID- 27497983
TI - Newly synthesized bis-benzimidazole compound 8 induces apoptosis, autophagy and
reactive oxygen species generation in HeLa cells.
AB - Compound 8 (C8) is a newly synthesized bis-benzimidazole derivative and exerts
significant anti-tumor activity in vitro. Previous studies demonstrated that C8
induced apoptosis and autophagy in human promyelocytic leukemia HL60 cells.
However, cytotoxicity study on human peripheral blood mononuclear cells (hPBMC)
showed that C8 exhibited less toxicity in normal cells. In this study, the
molecular mechanism of C8 on human cervical carcinoma HeLa cells was
investigated. The results showed that C8 inhibited the growth of HeLa cells and
triggered both apoptotic and autophagic cell death. Subsequent experiment also
indicated that reactive oxygen species (ROS) generation was induced in C8-treated
HeLa cells. Since ROS scavenger decreased the ratio of apoptotic and autophagic
cells, ROS generation contributed to C8-induced apoptosis and autophagy.
Furthermore, inhibitors of apoptosis and autophagy also reduced ROS generation,
respectively. Autophagy inhibition increased cell growth compared to C8-treated
group and attenuated apoptotic cell death, indicating that C8-induced autophagy
promoted apoptosis for cell death. However, the percentage of autophagic cells
was enhanced when limiting apoptosis process. Taken together, C8 induced ROS
mediated apoptosis and autophagy in HeLa cells, autophagy promoted apoptosis but
the former was antagonized by the latter. The data also gave us a new perspective
on the anti-tumor effect of C8.
PMID- 27497984
TI - Allelic diversity of S-RNase alleles in diploid potato species.
AB - KEY MESSAGE: The S-ribonuclease sequences of 16 S-alleles derived from diploid
types of Solanum are presented. A phylogenetic analysis and partial phenotypic
analysis support the conclusion that these are functional S-alleles. S
Ribonucleases (S-RNases) control the pistil specificity of the self
incompatibility (SI) response in the genus Solanum and several other members of
the Solanaceae. The nucleotide sequences of S-RNases corresponding to a large
number of S-alleles or S-haplotypes have been characterised. However,
surprisingly, few S-RNase sequences are available for potato species. The
identification of new S-alleles in diploid potato species is desirable as these
stocks are important sources of traits such as biotic and abiotic resistance. S
RNase sequences are reported here from three distinct diploid types of potato:
cultivated Solanum tuberosum Group Phureja, S. tuberosum Group Stenotomum, and
the wild species Solanum okadae. Partial S-RNase sequences were obtained from
pistil RNA by RT-PCR or 3'RACE (Rapid Amplification of cDNA Ends) using a
degenerate primer. Full-length sequences were obtained for two alleles by 5'RACE.
Database searches with these sequences identified 16 S-RNases in total, all of
which are novel. The sequence analysis revealed all the expected features of
functional S-RNases. Phylogenetic analysis with selected published S-RNase and S
like-RNase sequences from the Solanaceae revealed extensive trans-generic
evolution of the S-RNases and a clear distinction from S-like-RNases. Pollination
tests were used to confirm the self-incompatibility status and cross
compatibility relationships of the S. okadae accessions. All the S. okadae
accessions were found to be self-incompatible as expected with crosses amongst
them exhibiting both cross-compatibility and semi-compatibility consistent with
the S-genotypes determined from the S-RNase sequence data. The progeny analysis
of four semi-compatible crosses examined by allele-specific PCR provided further
confirmation that these are functional S-RNases.
PMID- 27497985
TI - Berberine attenuates oxidative stress and hepatocytes apoptosis via protecting
mitochondria in blunt snout bream Megalobrama amblycephala fed high-fat diets.
AB - High-fat diets may have favorable effects on growth and cost, but high-fat diets
often induce excessive fat deposition, resulting in liver damage. This study
aimed to identify the hepatoprotective of a Chinese herb (berberine) for blunt
snout bream (Megalobrama amblycephala). Fish were fed with a normal diet (LFD, 5
% fat), high-fat diet (HFD, 15 % fat) or berberine-supplemented diets (BSD, 15 %
fat with berberine 50 or 100 mg/kg level) for 8 weeks. After the feeding,
histology, oxidative status and mitochondrial function of liver were assessed.
The results showed that HFD caused fat accumulation, oxidative stress and
apoptosis in hepatocytes of fish. Hepatocytes in HFD group appeared to be
hypertrophied, with larger liver cells diameter than these of LFD group.
Berberine-supplemented diets could attenuate oxidative stress and hepatocytes
apoptosis. HFD induced the decreasing mitochondrial complexes activities and bulk
density and surface area density. Berberine improved function of mitochondrial
respiratory chain via increasing the complex activities. Moreover, the
histological results showed that berberine has the potential to repair
mitochondrial ultrastructural damage and elevate the density in cells. In
conclusion, our study demonstrated that berberine has attenuated liver damage
induced by the high fat mainly via the protection for mitochondria.
PMID- 27497986
TI - A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the
Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities.
AB - BACKGROUND/AIMS: Ovarian cancer is the most lethal gynecologic malignancy, and
there is an unmet clinical need to develop new therapies. Although showing
promising anticancer activity, Niclosamide may not be used as a monotherapy. We
seek to investigate whether inhibiting IGF signaling potentiates Niclosamide's
anticancer efficacy in human ovarian cancer cells. METHODS: Cell proliferation
and migration are assessed. Cell cycle progression and apoptosis are analyzed by
flow cytometry. Inhibition of IGF signaling is accomplished by adenovirus
mediated expression of siRNAs targeting IGF-1R. Cancer-associated pathways are
assessed using pathway-specific reporters. Subcutaneous xenograft model is used
to determine anticancer activity. RESULTS: We find that Niclosamide is highly
effective on inhibiting cell proliferation, cell migration, and cell cycle
progression, and inducing apoptosis in human ovarian cancer cells, possibly by
targeting multiple signaling pathways involved in ELK1/SRF, AP-1, MYC/MAX and
NFkB. Silencing IGF-1R exert a similar but weaker effect than that of
Niclosamide's. However, silencing IGF-1R significantly sensitizes ovarian cancer
cells to Niclosamide-induced anti-proliferative and anticancer activities both in
vitro and in vivo. CONCLUSION: Niclosamide as a repurposed anticancer agent may
be more efficacious when combined with agents that target other signaling
pathways such as IGF signaling in the treatment of human cancers including
ovarian cancer.
PMID- 27497987
TI - Effects of RNAs on chromatin accessibility and gene expression suggest RNA
mediated activation.
AB - The study of the interaction between RNA and DNA sequences in activating genes
has important significance for understanding the mechanisms of RNA-mediated
activation. Here, we used in vitro chromatin reconstitution approach to observe
whether RNAs increase DNase I digestion, plasmid transfection to observe whether
RNAs promote gene expression, and bioinformatics analysis to predict the binding
ability of RNAs to centromere DNA (constitutive heterochromatin). Synthetic RNAs
(23nt) that were complementary to mouse albumin gene and total liver RNA
increased DNase I digestion sensitivity of mouse albumin gene, suggesting that
RNAs can increase chromatin accessibility. Transcribed sense-antisense tandem Alu
elements activated an enhanced green fluorescent protein reporter gene after
stable transfection. Bioinformatics analysis showed that the binding strength of
RNA population to centromere DNAs is significantly lower than that of their
flanking sequences, which suggests that the centromere is not easily affected by
RNAs produced from other transcribed regions and may be the reason why
centromeres consist of constitutive heterochromatin. The results in this paper
illustrate that RNAs complementary to DNA sequences play roles in activating
genes. Since RNA is mainly produced from the cell's own DNA, the work presented
in this paper suggests that RNAs transcribed from DNA create feedback that
activates DNA transcription.
PMID- 27497988
TI - Thioredoxin-interacting protein regulates lipid metabolism via Akt/mTOR pathway
in diabetic kidney disease.
AB - Abnormal lipid metabolism contributes to the renal lipid accumulation, which is
associated with diabetic kidney disease, but its precise mechanism remains
unclear. The growing evidence demonstrates that thioredoxin-interacting protein
is involved in regulating cellular glucose and lipid metabolism. Here, we
investigated the effects of thioredoxin-interacting protein on lipid accumulation
in diabetic kidney disease. In contrast to the diabetic wild-type mice, the
physical and biochemical parameters were improved in the diabetic thioredoxin
interacting protein knockout mice. The increased renal lipid accumulation,
expression of acetyl-CoA carboxylase, fatty acid synthase and sterol regulatory
element binding protein-1, and phosphorylated Akt and mTOR associated with
diabetes in wild-type mice was attenuated in diabetic thioredoxin-interacting
protein knockout mice. Furthermore, thioredoxin-interacting protein knockout
significantly increased the expression of peroxisome proliferator-activated
receptor-alpha, acyl-coenzyme A oxidase 1 and carnitine palmitoyltransferaser 1
in diabetic kidneys. In vitro experiments, using HK-2 cells, revealed that
knockdown of thioredoxin-interacting protein inhibited high glucose-mediated
lipid accumulation, expression of acetyl-CoA carboxylase, fatty acid synthase and
sterol regulatory element binding protein-1, as well as activation of Akt and
mTOR. Moreover, knockdown of thioredoxin-interacting protein reversed high
glucose-induced reduction of peroxisome proliferator-activated receptor-alpha,
acyl-coenzyme A oxidase 1 and carnitine palmitoyltransferaser 1 expression in HK
2 cells. Importantly, blockade of Akt/mTOR signaling pathway with LY294002, a
specific PI3K inhibitor, replicated these effects of thioredoxin-interacting
protein silencing. Taken together, these data suggest that thioredoxin
interacting protein deficiency alleviates diabetic renal lipid accumulation
through regulation of Akt/mTOR pathway, thioredoxin-interacting protein may be a
potential therapeutic target for diabetic kidney disease.
PMID- 27497989
TI - Cell-specific paracrine actions of IL-6 family cytokines from bone, marrow and
muscle that control bone formation and resorption.
AB - Bone renews itself and changes shape throughout life to account for the changing
needs of the body; this requires co-ordinated activities of bone resorbing cells
(osteoclasts), bone forming cells (osteoblasts) and bone's internal cellular
network (osteocytes). This review focuses on paracrine signaling by the IL-6
family of cytokines between bone cells, bone marrow, and skeletal muscle in
normal physiology and in pathological states where their levels may be locally or
systemically elevated. These functions include the support of osteoclast
formation by osteoblast lineage cells in response to interleukin 6 (IL-6),
interleukin 11 (IL-11), oncostatin M (OSM) and cardiotrophin 1 (CT-1). In
addition it will discuss how bone-resorbing osteoclasts promote osteoblast
activity by secreting CT-1, which acts as a "coupling factor" on osteocytes,
osteoblasts, and their precursors to promote bone formation. OSM, produced by
osteoblast lineage cells and macrophages, stimulates bone formation via
osteocytes. IL-6 family cytokines also mediate actions of other bone formation
stimuli like parathyroid hormone (PTH) and mechanical loading. CT-1, OSM and LIF
suppress marrow adipogenesis by shifting commitment of pluripotent precursors
towards osteoblast differentiation. Ciliary neurotrophic factor (CNTF) is
released as a myokine from skeletal muscle and suppresses osteoblast
differentiation and bone formation on the periosteum (outer bone surface in
apposition to muscle). Finally, IL-6 acts directly on marrow-derived osteoclasts
to stimulate release of "osteotransmitters" that act through the cortical
osteocyte network to stimulate bone formation on the periosteum. Each will be
discussed as illustrations of how the extended family of IL-6 cytokines acts
within the skeleton in physiology and may be altered in pathological conditions
or by targeted therapies.
PMID- 27497990
TI - Polymorphisms of dopamine receptor genes and risk of visual hallucinations in
Parkinson's patients.
AB - BACKGROUND: Visual hallucinations (VHs) are frequent non-motor complication of
Parkinson's disease (PD), associated to a negative prognosis. Previous studies
showed an association between dopamine receptor (DR) gene (DR) variants and
psychosis in Alzheimer's disease, addictions, schizophrenia, and bipolar
disorder. However, there are only a few studies on DR variants and VHs in PD,
which did not provide conclusive results. OBJECTIVES: The present study aimed to
determine whether genetic differences of DR are associated with visual
hallucinations (VHs) in a cohort of Parkinson's disease (PD) patients. METHODS: A
case-control study of 84 PD subjects, 42 with and 42 without VHs,that were
matched for age, gender, disease duration, and dopaminergic medication was
conducted. Polymerase chain reaction for SNPs in both D1-like (DRD1A-48G [rs4532]
and C62T [rs686], DRD5T798C [rs6283]) and D2-like DR (DRD2G2137A [rs1800497] and
C957T [rs6277], DRD3G25A [rs6280] and G712C [rs1800828], DRD4C616G [rs747302] and
nR VNTR 48bp) analyzed genomic DNA. RESULTS: Patients carrying allele T at
DRD1C62T had an increased risk of VHs, expressed as OR (95 % CI, p value), of
10.7 (2.9-40, p = 0.0001). Moreover, patients with DRD1-48 GG and 62TT genotype
displayed shorter time to VHs, whereas a longer time to VHs was found in subjects
carrying the DRD4 CG alleles. CONCLUSIONS: PD patients with VHs display higher
frequency of DR SNPs associated with increased D1-like activity and decreased D2
like activity. Our data are in line with associations reported in other
neurodegenerative and psychiatric conditions. Results likely provide valuable
information for personalizing pharmacological therapy in PD patients.
PMID- 27497991
TI - Cost-utility analysis of 1-year treatment with adalimumab/standard care and
standard care alone for ulcerative colitis in Poland.
AB - PURPOSE: Until recently, surgery was the only remaining choice for moderate to
severe chronic ulcerative colitis patients who failed standard treatment or when
it was not tolerated. Anti-TNFalpha treatment is a new, non-invasive option for
the management of ulcerative colitis. The objective of this study was to assess
the cost-effectiveness of induction and maintenance treatment up to 1 year of
ulcerative colitis with adalimumab/standard care and standard care alone in
Poland. METHODS: A Markov model was used to estimate the expected costs and
effects of adalimumab/standard care and a standard care alone. For each treatment
option, the costs and quality adjusted life years were calculated to estimate the
incremental cost-utility ratio. The analysis was performed from the perspective
of the Polish public payer and society over a 30-year time horizon. Different
direct and indirect costs and utility values were assigned to the various model
health states. RESULTS: The treatment of ulcerative colitis patients with
adalimumab/standard care up to 1 year instead of a standard care alone resulted
in 0.14 additional years of life with full health (QALYs). The incremental cost
utility ratio of adalimumab/standard care compared to the standard care alone is
estimated to be 76,120 ?/QALY gained from NHF perspective and 71,457 ?/QALY
gained from social perspective. CONCLUSIONS: The biologic treatment of ulcerative
colitis patients with adalimumab/standard care is more effective but also more
costly compared with standard care alone.
PMID- 27497992
TI - In vitro promoter recognition by the catalytic subunit of plant phage-type RNA
polymerases.
AB - KEY MESSAGE: We identified sequence motifs, which enhance or reduce the ability
of the Arabidopsis phage-type RNA polymerases RPOTm (mitochondrial RNAP), RPOTp
(plastidial RNAP), and RPOTmp (active in both organelles) to recognize their
promoters in vitro with help of a 'specificity loop'. The importance of this data
for the evolution and function of the organellar RNA polymerases is discussed.
The single-subunit RNA polymerase (RNAP) of bacteriophage T7 is able to perform
all steps of transcription without additional transcription factors.
Dicotyledonous plants possess three phage-type RNAPs, RPOTm-the mitochondrial
RNAP, RPOTp-the plastidial RNAP, and RPOTmp-an RNAP active in both organelles.
RPOTm and RPOTp, like the T7 polymerase, are able to recognize promoters, while
RPOTmp displays no significant promoter specificity in vitro. To find out which
promoter motifs are crucial for recognition by the polymerases we performed in
vitro transcription assays with recombinant Arabidopsis RPOTm and RPOTp enzymes.
By comparing different truncated and mutagenized promoter constructs, we observed
the same minimal promoter sequence supposed to be needed in vivo for
transcription initiation. Moreover, we identified elements of core and flanking
sequences, which are of critical importance for promoter recognition and activity
in vitro. We further intended to reveal why RPOTmp does not efficiently recognize
promoters in vitro and if promoter recognition is based on a structurally defined
specificity loop of the plant enzymes as described for the yeast and T7 RNAPs.
Interestingly, the exchange of only three amino acids within the putative
specificity loop of RPOTmp enabled the enzyme for specific promoter transcription
in vitro. Thus, also in plant phage-type RNAPs the specificity loop is engaged in
promoter recognition. The results are discussed with respect to their relevance
for transcription in organello and to the evolution of RPOT enzymes including the
divergence of their functions.
PMID- 27497993
TI - Participation of protein kinases in cytotoxic and proapoptotic effects of
ethylene glycol ethers and their metabolites in SH-SY5Y cells.
AB - Ethylene glycol ethers (EGEs) are compounds widely used in many branches of
industry. Their toxicological profile in the peripheral tissues is relatively
well described, but little is known about their action on the central nervous
system (CNS). In this study, we evaluated the effect of 2-ethoxyethanol (EE), 2
butoxyethanol (BE), 2-phenoxyethanol (PHE) and their metabolites on necrotic
(estimated by cell viability and lactate dehydrogenase release) and apoptotic
(caspase-3 activity and mitochondrial membrane potential) processes and reactive
oxygen species' (ROS) production in human neuroblastoma (SH-SY5Y) cells. We have
shown that, similar to the peripheral tissues, EGE metabolites in most of the
performed assays revealed greater potential to damage than the parent compounds
in the CNS cells. Subsequently, we investigated the participation of some
selected protein kinases in the degenerative activity of PHE and its main
metabolite, phenoxyacetic acid (PHA). It has been found that a GSK3beta inhibitor
weakened the damaging effects of PHE and PHA in each of the performed assays.
Furthermore, the kinases, p38-MAPK, JNK-MAPK and PKC, had a significant role in
the cytotoxic and proapoptotic effects of PHA. These results indicate that the
neurotoxic effect of EGEs may stem from their impact on many intracellular signal
transduction pathways.
PMID- 27497994
TI - In vitro toxicity of cationic micelles and liposomes in cultured human hepatocyte
(HepG2) and lung epithelial (A549) cell lines.
AB - The aim of this study was to compare the effects of cationic micelle and liposome
drug delivery systems on liver and lung cells in a toxicological in vitro
screening model, with observations on cytotoxicity and genotoxicity. A screening
battery was established for assessment of a broad range of parameters related to
adverse effects. Clear concentration response effects were observed related to
impairment of mitochondrial function, membrane integrity and oxidative stress
markers, but no effect was observed on genotoxicity. The adverse effects were
highest for the liposomes. The High Content Screening seems optimal for initial
screening of adverse effects, and combined with standard cytotoxicity
measurements initial screening can be performed for predictive toxicological
screening.
PMID- 27497995
TI - The Metabolic Syndrome and the Phenotype of Frailty: A Causal Link?
PMID- 27497996
TI - Multi-methodological investigation of the variability of the microstructure of
HPMC hard capsules.
AB - The objective of this study was to analyze differences in the subtle
microstructure of three different grades of HMPC hard capsule shells using
mechanical, spectroscopic, microscopic and tomographic approaches. Dynamic
mechanical analysis (DMA), thermogravimetric analysis (TGA), vibrational
spectroscopic, X-Ray scattering techniques as well as environmental scanning
electron microscopy (ESEM) and optical coherence tomography (OCT) were used. Two
HPMC capsules manufactured via chemical gelling, one capsule shell manufactured
via thermal gelling and one thermally gelled transparent capsule were included.
Characteristic micro-structural alterations (associated manufacturing processes)
such as mechanical and physical properties relevant to capsule performance and
processability were thoroughly elucidated with the integration of data obtained
from multi-methodological investigations. The physico-chemical and physico
mechanical data obtained from a gamut of techniques implied that thermally gelled
HPMC hard capsule shells could offer an advantage in terms of machinability
during capsule filling, owing to their superior micro- and macroscopic structure
as well as specifically the mechanical stability under dry or humid conditions.
PMID- 27497997
TI - A systematic evaluation of mechanisms, material effects, and protein-dependent
differences on friction-related protein particle formation in formulation and
filling steps.
AB - Particle formation by physical degradation during the compounding step of
biopharmaceuticals is a common concern and found in vessels with bottom mounted
stirrers. It was potentially linked to sliding bearings, however, the exact
mechanism was still unclear. In this study, custom designed small scale bearings
in combination with an IgG1 antibody as model protein were used for
investigations of the degradation mechanism inside a bearing. Thereby, abrasion
of adsorbed proteins by contact sliding was identified as prevailing protein
degradation mechanism and was quantified by an increase in turbidity and by
monomer loss. As the protein degradation was highly dependent on combinations of
the material of the bearing and the buffer solution, a test system was introduced
which allowed to study these effects. Results from the test system using IgG1 and
recombinant human growth hormone confirmed a protective effect of Polysorbate 80
by a reduction of protein adsorption, which was strongest in combination with a
highly hydrophobic sliding material (PTFE). Finally, a comparison of degradation
products from various stresses by ATR-FTIR revealed a high similarity between
friction-related degradation products. Therefore, abrasion of adsorbed proteins
is very likely the prevailing physical degradation mechanism in processing steps
where contact sliding occurs.
PMID- 27497998
TI - Powder dispersion mechanisms within a dry powder inhaler using microscale
particle image velocimetry.
AB - The goal of this work was to evaluate the ability of Particle Image Velocimetry
(PIV) to visually assess dry powder dispersion within an inhaler. Herein, the
study reports particle movement characterization of entrained low-micron
particles within an inhaler to further scheme of potential mechanisms. Carrier
based DPI formulations were prepared and placed in a transparent model
Rotahaler(r) chamber for the aerosolization experiments. Then using the PIV, a
high-speed camera, the dried powder dispersion was directly observed and analyzed
for all, neat, binary and ternary systems. Powder dispersion mechanisms proposed
include drag force, impact with obstacle and particle-particle collision; these
different mechanisms depended on the powder flow properties. A revised ratio of
aerodynamic response time (tauA) to the mean time between collisions (tauC) was
found to be 6.8 indicating that particle collisions were of strong influence to
particle dispersion. With image analysis techniques, visualization of particle
flow pattern and collision regions was possible; suggesting that the various
mechanisms proposed did govern the powder dispersion.
PMID- 27497999
TI - A systematic review of community-based parenting interventions for adolescents
with challenging behaviours.
AB - Parenting skills training is an established means of treating challenging
behaviours among young children, but there has been limited research on its
efficacy when used to treat challenging adolescent behaviour. The aim of this
systematic review was to evaluate the efficacy and effectiveness of community
based parenting interventions designed for families with adolescents, as judged
in terms of increased knowledge and skills among parents, improvements in
adolescent behaviour, and program feasibility within community settings. Results
indicated that intervention group parents typically made greater gains than did
control group parents on measures of good parenting, with positive flow-on
effects to some aspects of challenging adolescent behaviours. Limited evidence
suggests that group and individual intervention formats may be equally effective
and that there is no advantage to the participation of the target adolescent in
the intervention.
PMID- 27498000
TI - Brief report: Overgeneral autobiographical memory in adolescent major depressive
disorder.
AB - The current study examined whether overgeneral autobiographical memory (OGM) bias
serves as a state-like marker of major depressive disorder (MDD) in adolescence
or whether it would also be observed in currently nondepressed adolescents with a
history of MDD. We examined differences in OGM to positive and negative cue words
between adolescents (aged 11-18 years) with current MDD (n = 15), remitted MDD (n
= 25), and no history of any depressive disorder (n = 25). Youth and their
parents were administered a structured diagnostic interview and adolescents
completed the autobiographical memory test. Compared to never depressed
adolescents, adolescents with current or remitted MDD recalled less specific
memories in response to positive and negative cue words. The difference between
the two MDD groups was small and nonsignificant. These findings suggest that OGM
is not simply a state-like marker in currently depressed adolescents, but is also
evident in adolescents with remitted MDD, indicating that it may represent a
trait-like vulnerability that increases risk for relapse.
PMID- 27498001
TI - Interparental conflict and adolescents' self-representations: The role of
emotional insecurity.
AB - Adolescents' signs of emotional insecurity in the context of interparental
conflict (IC) - emotional reactivity, internal representations (i.e.,
constructive/destructive; spillover) and behavioral responses (i.e., withdrawal;
inhibition; involvement) - were examined as mediators in the relation between IC
and adolescents' self-representations. Self-reported measures were filled out by
221 Portuguese adolescents (59.3% girls; Mage = 12.91), attending public
elementary and secondary schools. IC predicted less favorable self
representations. Adolescents' emotional reactivity and withdrawal mediated the
relation between IC and emotional and physical appearance self-representations,
while conflict spillover representations and constructive family representations
mediated associations between IC and instrumental self-representations. This
study emphasizes the importance of interparental conflict and adolescent
emotional insecurity in the construction of their self-representations, having
important theoretical and practical implications. It highlights the value of
analyzing the specific role of several emotional insecurity dimensions, and
informs practitioners' work aimed at promoting constructive conflict and adaptive
emotional regulation skills.
PMID- 27498002
TI - ATF7 ablation prevents diet-induced obesity and insulin resistance.
AB - The activating transcription factor (ATF)2 family of transcription factors
regulates a variety of metabolic processes, including adipogenesis and adaptive
thermogenesis. ATF7 is a member of the ATF2 family, and mediates epigenetic
changes induced by environmental stresses, such as social isolation and pathogen
infection. However, the metabolic role of ATF7 remains unknown. The aim of the
present study is to examine the role of ATF7 in metabolism using ATF7-dificeint
mice. Atf7(-/-) mice exhibited lower body weight and resisted diet-induced
obesity. Serum triglycerides, resistin, and adipose tissue mass were all
significantly lower in ATF7-deficient mice. Fasting glucose levels and glucose
tolerance were unaltered, but systemic insulin sensitivity was increased, by
ablation of ATF7. Indirect calorimetry revealed that oxygen consumption by Atf7(
/-) mice was comparable to that of wild-type littermates on a standard chow diet,
but increased energy expenditure was observed in Atf7(-/-) mice on a high-fat
diet. Hence, ATF7 ablation may impair the development and function of adipose
tissue and result in elevated energy expenditure in response to high-fat-feeding
obesity and insulin resistance, indicating that ATF7 is a potential therapeutic
target for diet-induced obesity and insulin resistance.
PMID- 27498003
TI - MiR-509-3-5p causes aberrant mitosis and anti-proliferative effect by suppression
of PLK1 in human lung cancer A549 cells.
AB - MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression
and play roles in DNA damage response (DDR). PLK1 is identified as a modulator of
DNA damage checkpoint. Although down-regulation of PLK1 by certain microRNAs has
been reported, little is known about the interplay between PLK1 and miR-509-3-5p
in DDR. Here we have demonstrated that miR-509-3-5p repressed PLK1 expression by
targeting PLK1 3'-UTR, thereby causing mitotic aberration and growth arrest of
human lung cancer A549 cells. Repression of PLK1 by miR-509-3-5p was further
evidenced by over-expression of miR-509-3-5p in A549, HepG2 and HCT116p53(-/-)
cancer cells, in which PLK1 protein was suppressed. Consistently, miR-509-3-5p
was stimulated, while PLK1 protein was down-regulated in A549 cells exposed to
CIS and ADR, suggesting that suppression of PLK1 by miR-509-3-5p is a component
of CIS/ADR-induced DDR pathway. Flow cytometry and immunofluorescence labeling
showed that over-expression of miR-509-3-5p in A549 induced G2/M arrest and
aberrant mitosis characterized by abnormal bipolar mitotic spindles, condensed
chromosomes, lagging DNA and chromosome bridges. In addition, over-expression of
miR-509-3-5p markedly blocked A549 cell proliferation and sensitized the cells to
CIS and ADR treatment. Taken together, miR-509-3-5p is a feasible suppressor for
cancer by targeting PLK1. Our data may provide aid in potential design of
combined chemotherapy and in our better understanding of the roles of microRNAs
in response to DNA damage.
PMID- 27498004
TI - Ulinastatin attenuates pulmonary endothelial glycocalyx damage and inhibits
endothelial heparanase activity in LPS-induced ARDS.
AB - Acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory
failure characterized by major pathologic mechanisms of increased microvascular
permeability and inflammation. The glycocalyx lines on the endothelial surface,
which determines the vascular permeability, and heparanase play pivotal roles in
the degradation of heparan sulfate (HS). HS is the major component of the
glycocalyx. The aim of this study is to examine the effects of Ulinastatin (UTI)
on vascular permeability and pulmonary endothelial glycocalyx dysfunction induced
by lipopolysaccharide (LPS). In our study, C57BL/6 mice and human umbilical vein
endothelial cells were stimulated with LPS to induce injury models. After 6 h of
LPS stimulation, pulmonary pathological changes, pulmonary edema, and vascular
permeability were notably attenuated by UTI. UTI inhibited LPS-induced
endothelial glycocalyx destruction and significantly decreased the production of
HS as determined by ELISA and immunofluorescence. UTI also reduced the active
form of heparanase (50 kDa) expression and heparanase activity. Moreover,
lysosome pH was investigated because heparanase (65 kDa) can be reduced easily in
its active form at 50 kDa in a low pH environment within lysosome. Results showed
that UTI could inhibit LPS-induced pH elevation in lysosome. In conclusion, UTI
protects pulmonary endothelial glycocalyx integrity and inhibits heparanase
activity during LPS-induced ARDS.
PMID- 27498005
TI - Cartilage oligomeric matrix protein prevents vascular aging and vascular smooth
muscle cells senescence.
AB - Aging-related vascular dysfunction contributes to cardiovascular morbidity and
mortality. Cartilage oligomeric matrix protein (COMP), a vascular extracellular
matrix protein, has been described as a negative regulatory factor for the
vascular aging-related processes including atherosclerosis and vascular
calcification. However, whether COMP is implicated in the process of vascular
aging remains unclear. Here, we identified a novel function of COMP in preventing
vascular aging and vascular smooth muscle cells (VSMCs) senescence. Firstly,
vascular COMP expression was decreased in three different senescence-accelerated
mouse models and was also declining with age. COMP(-/-) mice displayed elevated
senescence-associated markers expression, including p53, p21 and p16, in the
aortas compared with their wild type (WT) littermates. In accordance, COMP
deficiency induced aging-related vascular dysfunction as evidenced by the
significantly reduced phenylephrine-induced contraction and increased vascular
stiffness as evaluated by pulse wave velocity. The aortic wall of COMP(-/-) mice
was susceptible to senescence by displaying senescence-associated beta
galactosidase (SA beta-gal) activity induced by periadventitial application of
CaCl2 to the abdominal aorta. In vitro, COMP knockdown by small interfering (si)
RNA led to the elevation of p53, p21 and p16 as well as SA beta-gal activity in
VSMCs after H2O2 stimulation. VSMCs isolated from COMP(-/-) mice showed elevated
senescence-associated markers expression and supplement of COMP adenovirus to
COMP-deficient VSMCs greatly rescued cellular senescence. Taken together, these
findings revealed the essential role of COMP in retarding the development of
vascular aging and VSMC senescence.
PMID- 27498006
TI - Osterix plays a critical role in BMP4-induced promoter activity of connexin43.
AB - Osterix is an essential transcription factor for osteogenesis and is expressed in
osteoblasts. Although Osterix has been shown to be induced by bone morphogenetic
protein 4, the molecular mechanism underlying Osterix function during osteoblast
differentiation remains unclear. Connexin43 (Cx43) is the most abundant gap
junction protein in bone cells and plays a critical role in osteoblast
differentiation. However, little is known about the functional interactions
between Osterix and the Cx43 promoter. In the present study, we investigated the
relationship between Osterix and Cx43 in HEK293 and C2C12 cells. Cx43 expression
was significantly repressed by the addition of shRNA against Osterix, whereas
overexpression of Osterix resulted in enhanced Cx43 expression. Furthermore,
Osterix directly occupied the promoter region of Cx43 and subsequently increased
Cx43 promoter activity in a dose-dependent manner. In addition, phosphorylation
of the Ser76 and Ser80 residues in Osterix were found to be critical for its
activity on the Cx43 promoter. Our results suggest that Osterix plays an
important role in increasing bone morphogenetic protein 4-induced Cx43 activity.
PMID- 27498007
TI - Concomitant beige adipocyte differentiation upon induction of mesenchymal stem
cells into brown adipocytes.
AB - The accumulation of fat, which results in obesity, is related to many metabolic
disorders. Besides white and brown adipose tissue, beige adipose tissue has
recently been recognized as a new type of accumulated fat. Mesenchymal stem cells
(MSCs) have been shown to differentiate into brown adipocytes. Through analyzing
levels of mRNA and protein markers associated with beige adipocyte, we found
concomitant beige adipocyte differentiation upon induction of MSCs into brown
adipocytes in a defined medium containing triiodothyronine, insulin,
dexamethasone, and indomethacin. Moreover, we found that protein kinase A (PKA)
modulators regulated MSC differentiation into brown or beige adipocytes.
Activation of PKA by isobutylmethylxanthine or forskolin increased brown
adipocyte differentiation and reduced beige adipocyte differentiation, while
inactivation of PKA by KT-5720 or SC-3010 or the knockdown of PKA downstream cAMP
response element-binding protein (CREB) decreased brown adipocyte differentiation
and increased beige adipocyte differentiation. We also showed that increased
brown adipocyte differentiation was accompanied by an increase in mitochondrial
mass. In conclusion, we propose a model of beige/brown co-differentiation in MSCs
and develop a method for controlling this differentiation via PKA modulation.
PMID- 27498008
TI - The memory gene KIBRA is a bidirectional regulator of synaptic and structural
plasticity in the adult brain.
AB - Memory formation is associated with activity-dependent changes in synaptic
plasticity. The mechanisms underlying these processes are complex and involve
multiple components. Recent work has implicated the protein KIBRA in human
memory, but its molecular functions in memory processes remain not fully
understood. Here, we show that a selective overexpression of KIBRA in neurons
increases hippocampal long-term potentiation (LTP) but prevents the induction of
long-term depression (LTD), and impairs spatial long-term memory in adult mice.
KIBRA overexpression increases the constitutive recycling of AMPA receptors
containing GluA1 (GluA1-AMPARs), and favors their activity-dependent surface
expression. It also results in dramatic dendritic rearrangements in pyramidal
neurons both in vitro and in vivo. KIBRA knockdown in contrast, abolishes LTP,
decreases GluA1-AMPARs recycling and reduces dendritic arborization. These
results establish KIBRA as a novel bidirectional regulator of synaptic and
structural plasticity in hippocampal neurons, and of long-term memory, highly
relevant to cognitive processes and their pathologies.
PMID- 27498009
TI - Laparoendoscopic single-site cholecystectomy and common bile duct exploration
using conventional instruments.
AB - BACKGROUND: Optimization of quality of life is an important goal in the advanced
surgery. Herein we share our fifteen cases to demonstrate the feasibility of
scarless laparoendoscopic single-site common bile duct (CBD) exploration using
conventional instruments in the management of CBD stones. METHODS: Fifteen
patients (4 male) underwent transumbilical laparoendoscopic single-site
cholecystectomy and CBD exploration: the patients were diagnosed with CBD stones.
The endoscopic nasobiliary drainage (ENBD), endoscopic retrograde biliary
drainage (ERBD) or J-type tube was introduced into the CBD preoperatively or
intraoperatively. A 2-cm periumbilical incision was made for the placement of
three trocars. Conventional rigid laparoscopic instruments were solely used
throughout the procedure, and operative techniques were carried out in the same
fashion as for conventional T-tube-free laparoscopic cholecystectomy and CBD
exploration. RESULTS: The procedures were completed uneventfully in the mean
duration of 125.7 min. Three patients occurred pigtail J-tube displacement and
all three were later excreted safely in stool. CONCLUSIONS: Laparoendoscopic
single-site cholecystectomy and CBD exploration appears to be a technically
feasible alternative to standard laparoscopic procedure, and can be performed
using conventional laparoscopic instruments. Laparoscopic primary closure with
preoperative ENBD and ERBD tubes and with intraoperative J-tubes is safe and
feasible.
PMID- 27498010
TI - Nitrous oxide emissions in a membrane bioreactor treating saline wastewater
contaminated by hydrocarbons.
AB - The joint effect of wastewater salinity and hydrocarbons on nitrous oxide
emission was investigated. The membrane bioreactor pilot plant was operated with
two phases: i. biomass acclimation by increasing salinity from 10gNaClL(-1) to
20gNaClL(-1) (Phase I); ii. hydrocarbons dosing at 20mgL(-1) with a constant salt
concentration of 20gNaClL(-1) (Phase II). The Phase I revealed a relationship
between nitrous oxide emissions and salinity. During the end of the Phase I, the
activity of nitrifiers started to recover, indicating a partial acclimatization.
During the Phase II, the hydrocarbon shock induced a temporary inhibition of the
biomass with the suppression of nitrous oxide emissions. The results revealed
that the oxic tank was the major source of nitrous oxide emission, likely due to
the gas stripping by aeration. The joint effect of salinity and hydrocarbons was
found to be crucial for the production of nitrous oxide.
PMID- 27498011
TI - Towards high through-put biological treatment of municipal wastewater and
enhanced phosphorus recovery using a hybrid microfiltration-forward osmosis
membrane bioreactor with hydraulic retention time in sub-hour level.
AB - This work uncovers an important feature of the forward osmosis membrane
bioreactor (FOMBR) process: the decoupling of contaminants retention time (CRT)
and hydraulic retention time (HRT). Based on this concept, the capability of the
hybrid microfiltration-forward osmosis membrane bioreactor (MF-FOMBR) in
achieving high through-put treatment of municipal wastewater with enhanced
phosphorus recovery was explored. High removal of TOC and NH4(+)-N (90% and 99%,
respectively) was achieved with HRTs down to 47min, with the treatment capacity
increased by an order of magnitude. Reduced HRT did not affect phosphorus removal
and recovery. As a result, the phosphorus recovery capacity was also increased by
the same order. Reduced HRT resulted in increased system loading rates and thus
elevated concentrations of mixed liquor suspended solids and increased membrane
fouling. 454-pyrosequecing suggested the thriving of Bacteroidetes and
Proteobacteria (especially Sphingobacteriales Flavobacteriales and Thiothrix
members), as well as the community succession and dynamics of ammonium oxidizing
and nitrite oxidizing bacteria.
PMID- 27498012
TI - A novel approach of integrated bioprocessing of cane molasses for production of
prebiotic and functional bioproducts.
AB - In this work, the sugar industry by-product cane molasses was investigated as
feedstock for acceptor reactions by dextransucrase from Leuconostoc mesenteroides
MTCC 10508, leading to the biosynthesis of oligosaccharides. The starch industry
corn fiber residue was used as a source for acceptor molecules, maltose, in the
reaction. Production of approximately 124g oligosaccharides (DP3-DP6) per kg of
fresh molasses was achieved. Further, cane molasses based medium was demonstrated
as a sole carbon source for L. mesenteroides growth and dextransucrase
production. d-Fructose released by dextransucrase activity as processing by
product was transformed into the functional monosaccharide with zero caloric
value, d-psicose, by inducing its epimerization. Quantitative analysis
approximated 37g d-psicose per kg of fresh molasses. Thus, the study established
a novel approach of integrated bioprocessing of cane molasses into prebiotic and
functional food additives.
PMID- 27498013
TI - Bioethanol production by recycled Scheffersomyces stipitis in sequential batch
fermentations with high cell density using xylose and glucose mixture.
AB - Here, it is shown three-step investigative procedures aiming to improve pentose
rich fermentations performance, involving a simple system for elevated mass
production by Scheffersomyces stipitis (I), cellular recycle batch fermentations
(CRBFs) at high cell density using two temperature strategies (fixed at 30
degrees C; decreasing from 30 to 26 degrees C) (II), and a short-term adaptation
action seeking to acclimatize the microorganism in xylose rich-media (III).
Cellular propagation provided 0.52gdrycellweightgRS(-1), resulting in an
expressive value of 45.9gdrycellweightL(-1). The yeast robustness in CRBF was
proven by effective ethanol production, reaching high xylose consumption (81%)
and EtOH productivity (1.53gL(-1)h(-1)). Regarding the short-term adaptation, S.
stipitis strengthened its robustness, as shown by a 6-fold increase in xylose
reductase (XR) activity. The short fermentation time (20h for each batch) and the
fermentation kinetics for ethanol production from xylose are quite promising.
PMID- 27498014
TI - Valorization of food waste into hydroxymethylfurfural: Dual role of metal ions in
successive conversion steps.
AB - This study aimed to transform food waste into a value-added chemical,
hydroxymethylfurfural (HMF), and unravel the tangled effects induced by the metal
catalysts on each single step of the successive conversion pathway. The results
showed that using cooked rice and bread crust as surrogates of starch-rich food
waste, yields of 8.1-9.5% HMF and 44.2-64.8% glucose were achieved over SnCl4
catalyst. Protons released from metal hydrolysis and acidic by-products rendered
Bronsted acidity to catalyze fructose dehydration and hydrolysis of glycosidic
bond. Lewis acid site of metals could facilitate both fructose dehydration and
glucose isomerization via promoting the rate-limiting internal hydride shift,
with the catalytic activity determined by its electronegativity, electron
configuration, and charge density. Lewis acid site of a higher valence also
enhanced hydrolysis of polysaccharide. However, the metals also catalyzed
undesirable polymerization possibly by polarizing the carbonyl groups of sugars
and derivatives, which should be minimized by process optimization.
PMID- 27498016
TI - Learning in data-limited multimodal scenarios: Scandent decision forests and tree
based features.
AB - Incomplete and inconsistent datasets often pose difficulties in multimodal
studies. We introduce the concept of scandent decision trees to tackle these
difficulties. Scandent trees are decision trees that optimally mimic the
partitioning of the data determined by another decision tree, and crucially, use
only a subset of the feature set. We show how scandent trees can be used to
enhance the performance of decision forests trained on a small number of
multimodal samples when we have access to larger datasets with vastly incomplete
feature sets. Additionally, we introduce the concept of tree-based feature
transforms in the decision forest paradigm. When combined with scandent trees,
the tree-based feature transforms enable us to train a classifier on a rich
multimodal dataset, and use it to classify samples with only a subset of features
of the training data. Using this methodology, we build a model trained on MRI and
PET images of the ADNI dataset, and then test it on cases with only MRI data. We
show that this is significantly more effective in staging of cognitive
impairments compared to a similar decision forest model trained and tested on MRI
only, or one that uses other kinds of feature transform applied to the MRI data.
PMID- 27498015
TI - Increasing the impact of medical image computing using community-based open
access hackathons: The NA-MIC and 3D Slicer experience.
AB - The National Alliance for Medical Image Computing (NA-MIC) was launched in 2004
with the goal of investigating and developing an open source software
infrastructure for the extraction of information and knowledge from medical
images using computational methods. Several leading research and engineering
groups participated in this effort that was funded by the US National Institutes
of Health through a variety of infrastructure grants. This effort transformed 3D
Slicer from an internal, Boston-based, academic research software application
into a professionally maintained, robust, open source platform with an
international leadership and developer and user communities. Critical
improvements to the widely used underlying open source libraries and tools-VTK,
ITK, CMake, CDash, DCMTK-were an additional consequence of this effort. This
project has contributed to close to a thousand peer-reviewed publications and a
growing portfolio of US and international funded efforts expanding the use of
these tools in new medical computing applications every year. In this editorial,
we discuss what we believe are gaps in the way medical image computing is pursued
today; how a well-executed research platform can enable discovery, innovation and
reproducible science ("Open Science"); and how our quest to build such a software
platform has evolved into a productive and rewarding social engineering exercise
in building an open-access community with a shared vision.
PMID- 27498017
TI - Centre characteristics determine ambulatory care and referrals in patients with
spondyloarthritis.
AB - OBJECTIVE: To describe the variability in rheumatology visits and referrals to
other medical specialties of patients with spondyloarthritis (SpA) and to explore
factors that may influence such variability. METHODS: Nation-wide cross-sectional
study performed in 2009-2010. Randomly selected records of patients with a
diagnosis of SpA and at least one visit to a rheumatology unit within the
previous 2 years were audited. The rates of rheumatology visits and of referrals
to other medical specialties were estimated-total and between centres-in the
study period. Multilevel regression was used to analyse factors associated with
variability and to adjust for clinical and patient characteristics. RESULTS: 1168
patients' records (45 centres) were reviewed, mainly ankylosing spondylitis (55.2
%) and psoriatic arthritis (22.2 %). The patients had incurred in 5908 visits to
rheumatology clinics (rate 254 per 100 patient-years), 4307 visits to other
medical specialties (19.6 % were referrals from rheumatology), and 775 visits to
specialised nurse clinics. An adjusted variability in frequenting rheumatology
clinics of 15.7 % between centres was observed. This was partially explained by
the number of faculties and trainees. The adjusted intercentre variability for
referrals to other specialties was 12.3 %, and it was associated with urban
settings, number of procedures, and existence of SpA dedicated clinics; the
probability of a patient with SpA of being referred to other specialist may
increase up to 25 % depending on the treating centre. CONCLUSION: Frequenting
rheumatology clinics and referrals to other specialists significantly varies
between centres, after adjustment by patient characteristics.
PMID- 27498018
TI - On the electrophoretic mobility of succinoglycan modelled as a spherical
polyelectrolyte: From Hermans-Fujita theory to charge regulation in multi
component electrolytes.
AB - Literature interpretations of the electrophoretic mobility of spherical
polyelectrolytes are revisited using the capillary-electrophoresis data of Duval
et al. (2006) for the extracellular polysaccharide succinoglycan as an example.
Subtle changes in the polyelectrolyte mobility have recently been attributed to
new electrokinetic theories that feature multi-component electrolytes, charge
regulation, and the so-called polarization and relaxation phenomena. However,
these calculations exhibit several unusual trends that have yet to be explained,
and so the conclusions drawn from them are controversial. Here, independent
computations strengthen conclusions drawn from the original model of Duval et
al., i.e., the discrepancies between experiments and all the presently available
electrokinetic theories reflect changes in the conformation of succinoglycan
arising from changes in the electrolyte pH and ionic strength.
PMID- 27498020
TI - Engineering biodegradable micelles of polyethylenimine-based amphiphilic block
copolymers for efficient DNA and siRNA delivery.
AB - Polycationic micelles have shown advantageous properties as nucleic acid delivery
vectors both in vitro and in vivo. In contrast to polycationic micelles reported
so far, we designed particles integrating a sufficient nucleic acid condensation
capability by polycationic polyethylenimine (PEI) segments as well as only a mild
cytotoxic behavior. The micelles composed of a hydrophobic oligoester core with
glycolide units resulting in fast degradation after cellular internalization in
combination with PEG moieties acting as shielding agents. By grafting branched
25kDa polyethylenimine (PEI25) and poly(ethylene glycol) (PEG) on poly[(epsilon
caprolactone)-co-glycolide] (CG), amphiphilic PEI-CG-PEI and PEG-CG block
copolymers were used to form a series of micelles via self-assembly of PEI-CG-PEI
or co-assembly of both copolymers for DNA and siRNA delivery. This modular system
enabled a systematic investigation of different parameters and their synergetic
effects as different functions were introduced. The polyplex formation and serum
stability, cytotoxicity, and transfection activity could be tailored by changing
the CG chain length in PEI-based copolymer, incorporating PEG-CG, and varying the
N/P ratio. All micelle-based polyplex compositions showed high DNA transfection
activity according to reporter gene-expression and an exceptionally high
knockdown in siRNA delivery experiments. Remarkably, the GFP expression of >99%
cells was successfully knocked down by micelle-mediated siRNA interference,
resulting in a decrease of two orders of magnitude in fluorescence intensity.
Incorporation of PEG-CG in the micelles reduced the PEI-related cytotoxicity, and
markedly enhanced the serum stability of both DNA and siRNA polyplexes. Compared
with homo-PEI25, these micelles showed several advantages including the lower
toxicity, higher siRNA transfection efficiency and higher polyplex stability in
the presence of serum. This study therefore provides an effective approach to
tune the structure, property and function of polycationic micelles for efficient
DNA and siRNA delivery, which could contribute to the design and development of
novel non-viral transfection vectors with superb functionality.
PMID- 27498019
TI - Synthesis, characterization and evaluation of in vitro toxicity in hepatocytes of
linear polyesters with varied aromatic and aliphatic co-monomers.
AB - Polyesters are extensively used in drug delivery because of their controllable
biodegradation properties and perceived favorable cytocompatibility. However, new
ester-based materials are continually being sought which can be produced from
readily accessible monomers, which can be tuned for drug encapsulation and which
retain good cellular compatibilities. In this study, 5 polyesters of similar
molar mass were synthesized by reacting 1,10-decanediol with different ratios of
succinic acid/phenylsuccinic acid and the effect of the phenyl side-chain group
addition on polymer properties relevant to drug delivery was investigated. A
polymer with a 70/30 ratio of succinic acid and phenylsuccinic acid was selected
based on its ability to encapsulate a model dye in nanoparticle (NP)
formulations, and was found to be slowly degradable in phosphate buffered saline
(PBS) but more rapidly degraded in the presence of a lipase. The compatibility of
NP formulations of this polymer either with or without a Pluronic F68 stabilizing
coating was assessed in vitro using the C3A hepatocyte cell line. Cell viability
was assessed, at NP concentrations ranging from 4.68-300MUgmL-1 24h post
exposure, using the Alamar Blue, CDFA and Neutral Red assays. C3A cells
internalized both coated and uncoated polyester NPs to a similar extent, with
uptake observed to increase over time (10-1440min). Although cell viability was
>80% at the concentrations tested, in all assays, it was found that a Pluronic
F68 coated poly (decanediol-phenylsuccinate-co-succinate) stimulated significant
DNA damage driven by an oxidant mechanism, whereas the non-coated polyester
analogue and the Pluronic F68 alone had no effect. The results obtained suggest
that new polyesters can be synthesized with desirable properties from the
materials perspective but formulation with additional excipients requires careful
evaluation for drug delivery applications.
PMID- 27498021
TI - CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential.
AB - The CRISPR-Cas9 gene editing system has taken the biomedical science field by
storm, initiating rumors about future Nobel Prizes and heating up a fierce patent
war, but also making significant scientific impact. The Clustered Regularly
Interspaced Short Palindromic Repeats (CRISPR), together with CRISPR-associated
proteins (Cas) are a part of the prokaryotic adaptive immune system and have
successfully been repurposed for genome editing in mammalian cells. The CRISPR
Cas9 system has been used to correct genetic mutations and for replacing entire
genes, opening up a world of possibilities for the treatment of genetic diseases.
In addition, recently some new CRISPR-Cas systems have been discovered with
interesting mechanistic variations. Despite these promising developments, many
challenges have to be overcome before the system can be applied therapeutically
in human patients and enabling delivery technology is one of the key challenges.
Furthermore, the relatively high off-target effect of the system in its current
form prevents it from being safely applied directly in the human body. In this
review, the transformation of the CRISPR-Cas gene editing systems into a
therapeutic modality will be discussed and the currently most realistic in vivo
applications will be highlighted.
PMID- 27498022
TI - Development of an automated mid-scale parallel protein purification system for
antibody purification and affinity chromatography.
AB - Protein purification is often a bottleneck during protein generation for large
molecule drug discovery. Therapeutic antibody campaigns typically require the
purification of hundreds of monoclonal antibodies (mAbs) during the hybridoma
process and lead optimization. With the increase in high-throughput cloning,
faster DNA sequencing, and the use of parallel protein expression systems, a need
for high-throughput purification approaches has evolved, particularly in the
midsize range between 20 ml and 100 ml. To address this we modified a four
channel Gilson solid phase extraction system (referred to as MG-SPE) with
switching valves and sample holding loops to be able to perform standard affinity
purification using commercially available columns and micro-titer format deep
well blocks. By running 4 samples in parallel, the MG-SPE has the capacity to
purify up to 24 samples of greater than 50 ml each using a single-step affinity
purification protocol or a two-step protocol consisting of affinity
chromatography followed by desalting/buffer exchange overnight (~12 h run time).
Our evaluation of affinity purification using mAbs and Fc-fusion proteins from
mammalian cell supernatants demonstrates that the MG-SPE compared favorably with
industry standard systems for both protein quality and yield. Overall the system
is simple to operate and fills a void in purification processes where a simple,
efficient, automated system is needed for affinity purification of midsize
research samples.
PMID- 27498023
TI - Axitinib Versus Sorafenib in First-Line Metastatic Renal Cell Carcinoma: Overall
Survival From a Randomized Phase III Trial.
AB - BACKGROUND: In a randomized phase III trial in treatment-naive patients with
metastatic renal cell carcinoma (RCC), axitinib versus sorafenib yielded
numerically longer progression-free survival (median, 10.1 vs. 6.5 months; hazard
ratio [HR], 0.77; 1-sided P = .038) and significantly higher objective response
rate (32% vs. 15%; 1-sided P = .0006). In this article, we report overall
survival (OS) and updated safety results. PATIENTS AND METHODS: Previously
untreated patients with metastatic RCC (n = 288), stratified according to Eastern
Cooperative Oncology Group performance status (ECOG PS; 0 vs. 1), were randomized
2:1 to receive axitinib 5 mg twice per day (b.i.d.; n = 192) or sorafenib 400 mg
b.i.d. (n = 96). RESULTS: Median OS (95% confidence interval [CI]) was 21.7
months (18.0-31.7) with axitinib versus 23.3 months (18.1-33.2) with sorafenib
(stratified HR, 0.995; 95% CI, 0.731-1.356; 1-sided P = .4883). Among patients
with ECOG PS of 0, median OS was numerically longer with axitinib than with
sorafenib (41.2 vs. 31.9 months; HR, 0.811, 1-sided P = .1748), whereas among
patients with ECOG PS 1, median OS was shorter with axitinib than with sorafenib
(14.2 vs. 19.8 months; HR, 1.203; 1-sided; P = .7973). Incidence and severity of
common adverse events were consistent with previous reports. CONCLUSION: OS was
similar between axitinib and sorafenib in treatment-naive patients with
metastatic RCC, and no new safety signals emerged.
PMID- 27498025
TI - Neoblasts and the evolution of whole-body regeneration.
AB - The molecular mechanisms underlying whole-body regeneration are best understood
in the planarian flatworm Schmidtea mediterranea, where a heterogeneous
population of somatic stem cells called neoblasts provides new tissue for
regeneration of essentially any missing body part. Studies on Schmidtea have
provided a detailed description of neoblasts and their role in regeneration, but
comparatively little is known about the evolutionary history of these cells and
their underlying developmental programs. Acoels, an understudied group of aquatic
worms that are also capable of extensive whole-body regeneration, have arisen as
an attractive group to study the evolution of regenerative processes due to their
phylogenetically distant position relative to flatworms. Here, we review the
phylogenetic distribution of neoblast cells and compare their anatomical
locations, transcriptional profiles, and roles during regeneration in flatworms
and acoels to understand the evolution of whole-body regeneration. While the
general role of neoblasts appears conserved in species separated by 550 million
years of evolution, the extrinsic inputs they receive during regeneration can
vary, making the distinction between homology and convergence of mechanism
unclear. A more detailed understanding of the precise mechanisms behind whole
body regeneration in diverse phyla is necessary to understand the evolutionary
history of this powerful process.
PMID- 27498026
TI - Editorial commentary: The continuing evolution of primary PCI and clinical
guidelines.
PMID- 27498024
TI - Myocardial plasticity: cardiac development, regeneration and disease.
AB - The adult mammalian heart is unable to recover from myocardial cell loss due to
cardiac ischemia and infarction because terminally differentiated cardiomyocytes
proliferate at a low rate. However, cardiomyocytes in other vertebrate animal
models such as zebrafish, axolotls, newts and mammalian mouse neonates are
capable of de-differentiating in order to promote cardiomyocyte proliferation and
subsequent cardiac regeneration after injury. Although de-differentiation may
occur in adult mammalian cardiomyocytes, it is typically associated with diseased
hearts and pathologic remodeling rather than repair and regeneration. Here, we
review recent studies of cardiac development, regeneration and disease that
highlight how changes in myocardial identity (plasticity) is regulated and
impacts adaptive and maladaptive cardiac responses.
PMID- 27498027
TI - Isolation, structural analysis, and expression characteristics of the maize
nuclear factor Y gene families.
AB - NUCLEAR FACTOR-Y (NF-Y) has been shown to play an important role in growth,
development, and response to environmental stress. A NF-Y complex, which consists
of three subunits, NF-YA, NF-YB, and, NF-YC, binds to CCAAT sequences in a
promoter to control the expression of target genes. Although NF-Y proteins have
been reported in Arabidopsis and rice, a comprehensive and systematic analysis of
ZmNF-Y genes has not yet been performed. To examine the functions of ZmNF-Y genes
in this family, we isolated and characterized 50 ZmNF-Y (14 ZmNF-YA, 18 ZmNF-YB,
and 18 ZmNF-YC) genes in an analysis of the maize genome. The 50 ZmNF-Y genes
were distributed on all 10 maize chromosomes, and 12 paralogs were identified.
Multiple alignments showed that maize ZmNF-Y family proteins had conserved
regions and relatively variable N-terminal or C-terminal domains. The comparative
syntenic map illustrated 40 paralogous NF-Y gene pairs among the 10 maize
chromosomes. Microarray data showed that the ZmNF-Y genes had tissue-specific
expression patterns in various maize developmental stages and in response to
biotic and abiotic stresses. The results suggested that ZmNF-YB2, 4, 8, 10, 13,
and 16 and ZmNF-YC6, 8, and 15 were induced, while ZmNF-YA1, 3, 4, 6, 7, 10, 12,
and 13, ZmNF-YB15, and ZmNF-YC3 and 9 were suppressed by drought stress. ZmNF
YA3, ZmNF-YA8 and ZmNF-YA12 were upregulated after infection by the three
pathogens, while ZmNF-YA1 and ZmNF-YB2 were suppressed. These results indicate
that the ZmNF-Ys may have significant roles in the response to abiotic and biotic
stresses.
PMID- 27498028
TI - Protein kinase C-delta inhibitor, Rottlerin inhibits growth and survival of
mycobacteria exclusively through Shikimate kinase.
AB - The molecular bases of disease provide exceptional prospect to translate research
findings into new drugs. Nevertheless, to develop new and novel chemical entities
takes huge amount of time and efforts, mainly due to the stringent processes.
Therefore, drug repurposing is one of such strategies which is being used in
recent times to identify new pharmacophores. The essential first step in
discovery of the specific inhibitor with low toxicity is the identification and
elucidation of pathways exclusive to target pathogen. One such target is the
shikimate pathway, which is essential for algae, higher plants, bacteria and
fungi. Since, this enzyme system is absent in higher eukaryotes and in mammals,
the enzymes involved in the pathway provide an attractive target for the
development of potentially selective and non toxic antimicrobial agents. Since,
so far there is no specific inhibitor which is able to restrain mycobacterial
shikimate pathway; we expanded the use of a known kinase inhibitor; Rottlerin, in
order to predict the prototype in discovering the specific molecules against this
enzyme. For the first time we have shown that Rottlerin inhibits extracellular
mycobacteria by affecting Shikimate Kinase (SK) and this effect is further
enhanced during the intracellular infection due to the added effect of PKC- delta
down-regulation. The molecular docking of Rottlerin with both the mycobacterial
SKs, corroborated the inhibition data, and revealed that the effects of SK, in
slow and in fast grower mycobacteria are due to the changes in affinity of
binding with the drug.
PMID- 27498029
TI - Calotropin from Asclepias curasavica induces cell cycle arrest and apoptosis in
cisplatin-resistant lung cancer cells.
AB - Calotropin (M11), an active compound isolated from Asclepias curasavica L., was
found to exert strong inhibitory and pro-apoptotic activity specifically against
cisplatin-induced resistant non-small cell lung cancer (NSCLC) cells (A549/CDDP).
Molecular mechanism study revealed that M11 induced cell cycle arrest at the G2/M
phase through down-regulating cyclins, CDK1, CDK2 and up-regulating p53 and p21.
Furthermore, M11 accelerated apoptosis through the mitochondrial apoptotic
pathway which was accompanied by increase Bax/Bcl-2 ratio, decrease in
mitochondrial membrane potential, increase in reactive oxygen species production,
activations of caspases 3 and 9 as well as cleavage of poly ADP-ribose polymerase
(PARP). The activation and phosphorylation of JNK was also found to be involved
in M11-induced apoptosis, and SP610025 (specific JNK inhibitor) partially
prevented apoptosis induced by M11. In contrast, all of the effects that M11
induce cell cycle arrest and apoptosis in A549/CDDP cells were not significant in
A549 cells. Drugs with higher sensitivity against resistant tumor cells than the
parent cells are rather rare. Results of this study supported the potential
application of M11 on the non-small lung cancer (NSCLC) with cisplatin
resistance.
PMID- 27498030
TI - Crystal structure of the Epithiospecifier Protein, ESP from Arabidopsis thaliana
provides insights into its product specificity.
AB - Specifier proteins are important components of the glucosinolate-myrosinase
system, which mediate plant defense against herbivory and pathogen attacks. Upon
tissue disruption, glucosinolates are hydrolyzed to instable aglucones by
myrosinases, and then aglucones will rearrange to form defensive isothiocyanates.
Specifier proteins can redirect this reaction to form other products, such as
simple nitriles, epithionitriles and organic thiocyanates instead of
isothiocyanates based on the side chain structure of glucosinolate and the type
of the specifier proteins. Nevertheless, the molecular mechanism underlying the
different product spectrums of various specifier proteins was not fully
understood. Here in this study, we solved the crystal structure of the
Epithiospecifier Protein, ESP from Arabidopsis thaliana (AtESP) at 2.3 A
resolution. Structural comparisons with the previously solved structure of
thiocyanate forming protein, TFP from Thlaspi arvense (TaTFP) reveal that AtESP
shows a dimerization pattern different from TaTFP. Moreover, AtESP harbors a
slightly larger active site pocket than TaTFP and several residues around the
active site are different between the two proteins, which might account for the
different product spectrums of the two proteins. Together, our structural study
provides important insights into the molecular mechanisms of specifier proteins
and shed light on the basis of their different product spectrums.
PMID- 27498031
TI - Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe
hypoxia in 3T3-L1 cells.
AB - In-vitro investigation of the effects of hypoxia is limited by physical laws of
gas diffusion and cellular O2 consumption, making prolonged exposures to stable
O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects
of mild and severe hypoxia on triglyceride accumulation, lipid droplet size
distribution, spontaneous lipolysis and gene expression of adipocyte-specific
markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2
using a gas-permeable cultureware. Triglyceride accumulation, expression of genes
characteristic for advanced adipocyte differentiation and involvement of key
lipogenesis enzymes were assessed after exposures. Lipogenesis increased by 375%
under mild hypoxia, but dropped by 43% in severe hypoxia. Mild, but not severe,
hypoxia increased formation of large lipid droplets 6.4 fold and strongly induced
gene expression of adipocyte-specific markers. Spontaneous lipolysis increased by
488% in mild, but only by 135% in severe hypoxia. Inhibition of ATP-dependent
citrate lyase suppressed hypoxia-induced lipogenesis by 81% and 85%. Activation
of HIF inhibited lipogenesis by 59%. Mild, but not severe, hypoxia stimulates
lipolysis and promotes adipocyte differentiation, probably through excess of
acetyl-CoA originating from tricarboxylic acid cycle independently of HIF
activation.
PMID- 27498032
TI - Let-7a inhibits tumor cell growth and metastasis by directly targeting RTKN in
human colon cancer.
AB - Colorectal cancer (CRC) is the third most common cancer worldwide, with high
morbidity. MicroRNAs (miRNAs) are endogenous small RNAs that play important roles
in regulating multiple biological and pathologic processes. The differential
expression of miRNAs in CRC was first reported in 2003. Accumulated evidence
indicates that lethal-7a (let-7a, miRNA) generally functions as a tumor
suppressor in several human cancers. However, the role of let-7a in human colon
cancer remains unclear. The aim of this study was to investigate the biological
functions of let-7a and its potential role in colon cancer. We first discovered
that let-7a level was significantly decreased in colon cancer tissues and cell
lines (HT-29, HCT-116, LoVo, SW480, and SW620). To explore the effects of let-7a
on colon cancer, let-7a over-expressed HCT-116 and SW620 cells were constructed.
Further studies demonstrated that over-expressed let-7a could remarkably inhibit
HCT-116 and SW620 cell growth and metastasis by directly down-regulating Rhotekin
(RTKN). When RTKN was reintroduced into let-7a mimic transfected HCT-116 or SW620
cells, the inhibition effects of let-7a on colon cancer cell growth and
metastasis were markedly reversed. In conclusion, our research shows that let-7a
can inhibit tumor cell growth and metastasis by directly targeting RTKN in human
colon cancer.
PMID- 27498033
TI - Dehydroascorbic acid-induced endoplasmic reticulum stress and leptin resistance
in neuronal cells.
AB - Due to its anti-obesity effects, an adipocyte-derived hormone, leptin, has become
important for the treatment of obesity. However, most obese subjects are in a
state of leptin resistance, and endoplasmic reticulum (ER) stress is suggested to
be involved in the pathophysiology of leptin resistance. Dehydroascorbic acid
(DHAA), an oxidized form of vitamin C, was found to be increased in diabetes. In
the present study, we investigated the possible effects of DHAA on the activation
of ER stress and leptin resistance. A human neuroblastoma cell line, stably
transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb), was treated with DHAA.
We found that DHAA upregulated ER stress-related genes such as GRP78, CHOP, and
spliced XBP1. Moreover, leptin-induced STAT3 phosphorylation was hindered by
DHAA. These results suggested that increases in the levels of DHAA might be
harmful to neurons, contributing to defective leptin-responsive signaling.
PMID- 27498034
TI - [Traumatic hand injuries in children].
AB - Hand injuries in children are frequent in pediatric emergencies. Epidemiology of
hand injuries in children depends on age and social context. The management of
these injuries requires experienced pediatrics in order to obtain a functional
hand to preserve the potential growth and to reduce the risk of cosmetic
sequelae. We will describe the specificities of hand trauma in children and their
therapeutic principles.
PMID- 27498035
TI - A new Western blot assay for the detection of porcine cytomegalovirus (PCMV).
AB - Porcine cytomegalovirus (PCMV) may be harmful for human recipients if
xenotransplantation using pig cell, tissue or organ will be performed
transmitting the virus from donor pigs to human recipients. PCMV is widespread in
pigs and closely related to human pathogenic herpesviruses, however there are no
data concerning infection of humans. In contrast, recently it had been shown that
transplantation of organs from pigs infected with PCMV into non-human primate
recipients resulted in a significant reduction of the survival time compared with
the transplantation of organs from uninfected pigs. To prevent transmission of
PCMV in future pig to human xenotransplantations, sensitive and specific
detection methods should be used. Here a new Western blot assay using recombinant
proteins corresponding to two domains of the glycoprotein gB of PCMV is
described. With this assay, the presence of PCMV-specific antibodies in different
pig breeds was analysed. Antibodies were detected in a high percentage of
animals, in one breed up to 85%.
PMID- 27498036
TI - An avian influenza H5N1 virus vaccine candidate based on the extracellular domain
produced in yeast system as subviral particles protects chickens from lethal
challenge.
AB - Highly pathogenic avian influenza is an on-going problem in poultry and a
potential human pandemic threat. Pandemics occur suddenly and vaccine production
must be fast and effective to be of value in controlling the spread of the virus.
In this study we evaluated the potential of a recombinant protein from the
extracellular domain of an H5 hemagglutinin protein produced in a yeast
expression system to act as an effective vaccine. Protein production was
efficient, with up to 200 mg purified from 1 L of culture medium. We showed that
the deletion of the multibasic cleavage site from the protein improves
oligomerization and, consequentially, its immunogenicity. We also showed that
immunization with this deleted protein protected chickens from challenge with a
highly pathogenic avian influenza H5N1 virus. Our results suggest that this
recombinant protein produced in yeast may be an effective vaccine against H5N1
virus in poultry.
PMID- 27498039
TI - Your misery is no longer my pleasure: Reduced schadenfreude in Huntington's
disease families.
AB - Schadenfreude - pleasure at others' misfortunes - has been systematically related
to ventral striatum activity. This brain region is affected early in individuals
with manifest and pre-manifest Huntington's disease (HD). However, the experience
of schadenfreude has not yet been investigated in HD. In this study, 21 manifest
HD patients, 19 first-degree asymptomatic relatives, and 23 healthy controls
performed an experimental task designed to trigger schadenfreude, envy (another
social emotion acting as an affective control condition), and control situations.
Both HD patients and first-degree relatives experienced lower schadenfreude in
response to others' misfortunes, with no group differences in ratings of envy and
control conditions. These results offer unprecedented evidence of a highly
specific impairment in reward processing, extending previous reports in manifest
and pre-manifest HD individuals. Moreover, these findings suggest that early
striatal impairments may be related to reduced feelings of schadenfreude. In sum,
our work contributes to the understanding of emotional impairments in early
stages of HD, while shedding light on their neural correlates.
PMID- 27498037
TI - Animal models of resistance exercise and their application to neuroscience
research.
AB - BACKGROUND: Numerous studies have demonstrated that participation in regular
resistance exercise (e.g., strength training) is associated with improvements in
mental health, memory, and cognition. However, less is known about the
neurobiological mechanisms mediating these effects. The goal of this mini-review
is to describe and evaluate the available animal models of resistance exercise
that may prove useful for examining CNS activity. NEW METHOD: Various models have
been developed to examine resistance exercise in laboratory animals. COMPARISON
WITH EXISTING METHODS: Resistance exercise models vary in how the resistance
manipulation is applied, either through direct stimulation of the muscle (e.g.,
in situ models) or through behavior maintained by operant contingencies (e.g.,
whole organism models). Each model presents distinct advantages and disadvantages
for examining central nervous system (CNS) activity, and consideration of these
attributes is essential for the future investigation of underlying
neurobiological substrates. RESULTS: Potential neurobiological mechanisms
mediating the effects of resistance exercise on pain, anxiety, memory, and drug
use have been efficiently and effectively investigated using resistance exercise
models that minimize stress and maximize the relative contribution of resistance
over aerobic factors. CONCLUSIONS: Whole organism resistance exercise models that
(1) limit the use of potentially stressful stimuli and (2) minimize the
contribution of aerobic factors will be critical for examining resistance
exercise and CNS function.
PMID- 27498038
TI - Hydrocarbon stapled B chain analogues of relaxin-3 retain biological activity.
AB - Relaxin-3 or insulin-like peptide 7 (INSL7) is the most recently discovered
relaxin/insulin-like family peptide. Mature relaxin-3 consists of an A chain and
a B chain held by disulphide bonds. According to structure activity relationship
studies, the relaxin-3 B chain is more important in binding and activating the
receptor. RXFP3 (also known as Relaxin-3 receptor 1, GPCR 135, somatostatin- and
angiotensin- like peptide receptor or SALPR) was identified as the cognate
receptor for relaxin-3 by expression profiles and binding studies. Recent studies
imply roles of this system in mediating stress and anxiety, feeding, metabolism
and cognition. Stapling of peptides is a technique used to develop peptide drugs
for otherwise undruggable targets. The main advantages of stapling include,
increased activity due to reduced proteolysis, increased affinity to receptors
and increased cell permeability. Stable agonists and antagonists of RXFP3 are
crucial for understanding the physiological significance of this system. So far,
agonists and antagonists of RXFP3 are peptides. In this study, for the first
time, we have introduced stapling of the relaxin-3 B chain at 14th and 18th
positions (14s18) and 18th and 22nd position (18s22). These stapled peptides
showed greater helicity than the unstapled relaxin-3 B chain in circular
dichroism analysis. Both stapled peptides bound RXFP3 and activated RXFP3 as
observed in an inhibition of forskolin-induced cAMP assay and a ERK1/2 activation
assay, although with different potencies. Therefore, we conclude that stapling of
the relaxin3 B chain does not compromise its ability to activate RXFP3 and is a
promising method for developing stable peptide agonists and antagonists of RXFP3
to aid relaxin-3/RXFP3 research.
PMID- 27498040
TI - Am I seeing myself, my friend or a stranger? The role of personal familiarity in
visual distinction of body identities in the human brain.
AB - Several brain regions appear to play a role in representing different body
identities. The specific contribution of each of these regions is still unclear,
however. Here we investigated which brain areas enable the visual distinction
between self and other bodies of different familiarity, and between familiar and
unfamiliar other individuals, and moreover, where identity-specific information
on the three individuals was encoded. Participants were confronted with
standardized headless human body stimuli either showing the participant's own, a
personally familiar or an unfamiliar other body, while performing a luminance
discrimination task. Employing multivariate pattern analysis, we were able to
identify areas that allowed for the distinction of self from personal familiar
other bodies within the medial prefrontal cortex (mPFC) and posterior cingulate
cortex/precuneus. Successful distinction of self from unfamiliar others was
possible in the left middle frontal gyrus, the right inferior frontal gyrus, the
left pre-supplementary motor area and the right putamen. Personally familiar
others could be distinguished from unfamiliar others in the right temporoparietal
junction (TPJ). An analysis of identity-specific information revealed a spatial
gradient ranging from inferior posterior to superior anterior portions of the
mPFC that was associated with encoding identity-related information for self via
familiar to unfamiliar other bodies, respectively. Furthermore, several midline
and frontal regions encoded information on more than one identity. The TPJ's role
in deviance detection was underlined, as only identity-specific information on
unfamiliar others was encoded here. Together, our findings suggest substantial
spatial overlap in neural correlates of self and other body representation and
thus, support the hypothesis of a socially-related representation of the self.
PMID- 27498041
TI - Different FDG-PET metabolic patterns at single-subject level in the behavioral
variant of fronto-temporal dementia.
AB - BACKGROUND: The diagnosis of probable behavioral variant of fronto-temporal
dementia (bvFTD) according to current criteria requires the imaging evidence of
frontal and/or anterior temporal atrophy or hypoperfusion/hypometabolism.
Different variants of this pattern of brain involvement may, however, be found in
individual cases, supporting the presence of heterogeneous phenotypes. OBJECTIVE:
We examined in a case-by-case approach the FDG-PET metabolic patterns of patients
fulfilling clinical criteria for probable bvFTD, assessing the presence and
frequency of specific FDG-PET features. MATERIALS AND METHODS: Fifty two FDG-PET
scans of probable bvFTD patients were retrospectively analyzed together with
clinical and neuropsychological data. Neuroimaging experts rated the FDG-PET
hypometabolism maps obtained at the single-subject level with optimized voxel
based Statistical Parametric Mapping (SPM). The functional metabolic
heterogeneity was further tested by hierarchical cluster analysis and principal
component analysis (PCA). RESULTS: Both the SPM maps and cluster analysis
identified two major variants of cerebral hypometabolism, namely the "frontal"
and the "temporo-limbic", which were correlated with different cognitive
profiles. Executive and language deficits were the cognitive hallmark in the
"frontal" subgroup, while poor encoding and recall on long-term memory tasks was
typical of the "temporo-limbic" subgroup. DISCUSSION: SPM single-subject analysis
indicates distinct patterns of brain dysfunction in bvFTD, coupled with specific
clinical features, suggesting different profiles of neurodegenerative
vulnerability. These findings have important implications for the early diagnosis
of bvFTD and for the application of the recent international consensus criteria.
PMID- 27498042
TI - Distribution of type VI collagen in association with osteoblast lineages in the
groove of Ranvier during rat postnatal development.
AB - In the groove of Ranvier (GOR), osteoblast lineages form bone bark, which
develops into endosteal cortical bone. This ossification process is thought to be
regulated by the microenvironment in the GOR. Type VI collagen (Col VI), an
extracellular matrix (ECM) protein found in the periosteum/perichondrium,
mediates osteoblast differentiation via the cell-surface receptor neural/glial
antigen 2 (NG2) chondroitin sulfate proteoglycan. In order to clarify the
function of Col VI during osteoblast differentiation in the GOR, in the present
study, we examined the distribution of Col VI and osteoblast lineages expressing
NG2 in the rat tibia proximal end during postnatal growing periods by
immunohistochemistry. Our data revealed that Col VI accumulated in the ECM of the
GOR middle layer and that Col VI accumulation was reduced and disappeared in the
inner and middle lower regions. Runt-related transcription factor 2
immunoreactive pre-osteoblasts expressed NG2 in Col VI-immunopositive areas.
However, Osterix-immunoreactive mature osteoblasts were only found in the Col VI
immunonegative area. These findings indicate that Col VI provided a
characteristic microenvironment in the GOR and that NG2-Col VI interactions may
regulate the differentiation of osteoblast lineages prior to terminal maturation.
PMID- 27498043
TI - The importance of surfactant proteins-New aspects on macrophage phagocytosis.
AB - Surfactant and its components have multiple functions. The so called collectins
are surfactant proteins which opsonize bacteria and improve pulmonary host
defense via the phagocytosis and clearance of microorganisms and particles. In
this special issue of the Annals of Anatomy a new surfactant protein, Surfactant
Associated 3, is highlighted. As outlined in this mini review Surfactant
Associated 3 is regarded as an enhancer of phagocytosis. In addition, the role
played by SP-A is updated and open research questions raised.
PMID- 27498044
TI - The Effect of Waiting Times for Postoperative Radiotherapy on Outcomes for Women
Receiving Partial Mastectomy for Breast Cancer: a Systematic Review and Meta
Analysis.
AB - AIMS: To determine the effect of delay in postoperative radiotherapy on local
recurrence and overall survival in women receiving partial mastectomy for breast
cancer. MATERIALS AND METHODS: This was a systematic review and meta-analysis of
published literature. Relevant reports were identified from MEDLINE, EMBASE and
the Cochrane Register of Controlled Trials in all languages from 1975 to April
2015, in addition to the abstracts from the annual meetings of major radiotherapy
conferences from 2000 to 2011. Reference lists were hand searched to find
additional relevant reports and OvidSP's 'Find Citing' function was used to find
studies citing papers identified in the primary search. Studies were included if
they met the following criteria: (i) all patients received partial mastectomy and
radiotherapy, (ii) a delay from surgery to radiotherapy was reported and (iii)
one or more of local control/failure and/or survival were reported. Observational
studies and randomised controlled trials were included. Studies including
patients with in situ disease were excluded. Studies were classified as high
quality if they adequately controlled for factors known to be associated with the
outcomes of interest. Study quality was independently assessed by three authors.
Initial disagreements about three studies were resolved by consensus. Only high
quality studies were included in the primary analysis. Delay was modelled as a
continuous variable and the relative risk of local recurrence and the relative
risk of death are reported per month of delay. The study results were combined
using a fixed-effects model. RESULTS: Thirty-four relevant publications including
79 616 patients were identified in the systematic review. Ten high-quality
publications reported on local recurrence (13 291 patients) and four high-quality
studies reported on overall survival (2207 patients). The relative risk of local
recurrence per month of delay was 1.08 (95% confidence interval 1.02-1.14). The
relative risk of death per month of delay was 0.99 (95% confidence interval 0.94
1.05). CONCLUSIONS: Delays in post-lumpectomy radiotherapy are associated with a
significant increase in the risk of local recurrence. We recommend that waiting
times for radiotherapy should be kept as short as reasonably achievable.
PMID- 27498045
TI - Withanolides from leaves of cultivated Acnistus arborescens.
AB - Seven withanolides, including four previously unknown, were isolated from the
acetone and ethanol extracts of cultivated specimens of Acnistus arborescens.
These four compounds were identified as rel-(18R,22R)-5beta,6beta:18beta,20
diepoxy-3beta,18alpha-dimethoxy-4beta-hydroxy-1-oxowith-24-enolide, rel-(20R,22R)
5beta,6beta-epoxy-4beta,16alpha,20-trihydroxy-1-oxowitha-2,24dienolide, rel
(20R,22R)-16alpha-acetoxy-6alpha-chloro-4beta,5beta,20-trihydroxy-1-oxowitha-2,24
dienolide and rel-(20R,22R)-16alpha-acetoxy-20-hydroxy-1-oxowitha-2,5,24
trienolide. Their structures were elucidated by interpretation of spectroscopic
data (1D and 2D NMR), HRESIMS experiments and comparison with published data for
similar compounds. Cytotoxicity of the isolated compounds was evaluated against a
panel of four tumor cell lines (HL-60, HCT-116, SF-268 and PANC-1). Withanolide D
was the most active, with an IC50 value in the range of 0.3-1.7 MUM, rel
(18R,22R)-5beta,6beta:18beta,20-diepoxy-3beta,18alpha-dimethoxy-4beta-hydroxy-1
oxowith-24-enolide and rel-(20R,22R)-5beta,6beta-epoxy-4beta,16alpha,20
trihydroxy-1-oxowitha-2,24dienolide were moderately active, while all the others
were non-cytotoxic.
PMID- 27498046
TI - Absolute configurations of phytotoxic inuloxins B and C based on experimental and
computational analysis of chiroptical properties.
AB - The absolute configuration of phytotoxins inuloxins B and C, produced by Inula
viscosa, and with potential herbicidal activity for the management of parasitic
plants, has been determined by Time-dependent density functional theory
computational prediction of electronic circular dichroism and optical rotatory
dispersion spectra. The inuloxin B has been converted to its 5-O-acetyl
derivative, which due to its more constrained conformational features facilitated
the computational analysis of its chiroptical properties. The analysis based on
experimental and computed data led to assignment of absolute configuration to
naturally occurring (+)-inuloxin B and (-)-inuloxin C as (7R,8R,10S,11S) and
(5S,7S,8S,10S), respectively.
PMID- 27498047
TI - RACK1 overexpression associates with pancreatic ductal adenocarcinoma growth and
poor prognosis.
AB - OBJECTIVES: The receptor for activated protein kinase C (RACK1) is a scaffold
protein involved in multiple intracellular signal pathways. Previous studies have
shown that RACK1 is associated with the progression of multiple cancer types,
including hepatocellular carcinoma and gastric cancer. However, the role of RACK1
in human pancreatic ductal adenocarcinoma (PDAC) remains unclear. METHODS: In
this study, the expression of RACK1 was evaluated by Western blot analysis in 8
paired fresh PDAC tissues and immunohistochemistry on 179 paraffin-embedded
slices. Then, we used Fisher exact test to analyze the correlation between RACK1
expression and clinicopathological characteristics. Starvation and re-feeding
assay was used to assess cell cycle. Western blot, CCK8, flow cytometry assays,
and colony formation analyses demonstrated that RACK1 played an essential role in
PDAC development. Annexin-V/PI apoptotic assay and western blot showed that RACK1
was involved in regulating the apoptosis of PDAC cells. RESULTS: RACK1 was highly
expressed in PDAC tissues and cell lines and was significantly associated with
multiple clinicopathological factors. Univariate and multivariate analyses showed
that high RACK1 expression was identified to be an independent prognostic factor
for PDAC patients' survival. In vitro, serum starvation-refeeding experiment
suggested that RACK1 was upregulated in proliferating PDAC cells, together with
the percentage of cells at the S phase, and was correlated with the expression of
Cyclin D1. Moreover, Overexpression of RACK1 facilitated the proliferation and
cell cycle progression of PDAC cells, while downregulation of RACK1 induced
growth impairment, G1/S cell cycle arrest and apoptosis in PDAC cells. Silencing
RACK1 decreased bcl-2 expression, increased cleaved caspase3 expression level and
induced the apoptosis of PDAC cells. CONCLUSIONS: Our results suggest that RACK1
could play an important role in the tumorigenesis of PDAC and serve as a
potential therapeutical target in PDAC treatment.
PMID- 27498048
TI - The genomic profile of pancreatic adenocarcinoma and its relationship to
metastatic disease.
PMID- 27498049
TI - Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling
Gradient.
AB - By using the sensitivity of single-molecule fluorescent in situ hybridization, we
have precisely quantified the levels and defined the temporal and spatial
distribution of Hedgehog signaling activity during embryonic skin development and
discovered that there is a Hedgehog signaling gradient along the proximal-distal
axis of developing hair follicles. To explore the contribution of Hedgehog
receptors Ptch1 and Ptch2 in establishing the epidermal signaling gradient, we
quantitated the level of pathway activity generated in Ptch1- and Ptch1;Ptch2
deficient skin and defined the contribution of each receptor to regulation of the
levels of Hedgehog signaling identified in wild-type skin. Moreover, we show that
both the cellular phenotype and level of pathway activity featured in Ptch1;Ptch2
deficient cells faithfully recapitulates the Peak level of endogenous Hedgehog
signaling detected at the base of developing follicles, where the concentration
of endogenous Shh is predicted to be highest. Taken together, these data show
that both Ptch1 and Ptch2 play a crucial role in sensing the concentration of
Hedgehog ligand and regulating the appropriate dose-dependent response.
PMID- 27498050
TI - A Co-Drug of Butyric Acid Derived from Fermentation Metabolites of the Human Skin
Microbiome Stimulates Adipogenic Differentiation of Adipose-Derived Stem Cells:
Implications in Tissue Augmentation.
AB - We show that Staphylococcus epidermidis, a commensal bacterium in the human skin
microbiome, produces short-chain fatty acids by glycerol fermentation that can
induce adipogenesis. Although the antimicrobial and anti-inflammatory activities
of short-chain fatty acids have been previously well characterized, little is
known about the contribution of short-chain fatty acids to the adipogenic
differentiation of adipose-derived stem cells (ADSCs). We show that ADSCs
differentiated into adipocytes and accumulated lipids in the cytoplasm when
cultured with butyric acid, a principal short-chain fatty acid in the
fermentation metabolites of S. epidermidis. Additionally, a co-drug, butyric acid
2-(2-butyryloxyethoxy) ethyl ester (BA-DEG-BA), released active butyric acid when
it was intradermally injected into mouse ears and induced ADSC differentiation,
characterized by an increased expression of cytoplasmic lipids and perilipin A.
The BA-DEG-BA-induced adipogenic differentiation was mediated via peroxisome
proliferator-activated receptor gamma. Furthermore, intradermal injection of
ADSCs along with BA-DEG-BA into mouse ears markedly enhanced the adipogenic
differentiation of ADSCs, leading to dermal augmentation. Our study introduces BA
DEG-BA as an enhancer of ADSC adipogenesis and suggests an integral interaction
between the human skin microbiome and ADSCs.
PMID- 27498051
TI - [Not Available].
PMID- 27498052
TI - Esthetic management of anterior dental anomalies: A clinical case.
AB - Many types of dental abnormality can be observed in the anterior sectors, where
they can cause genuine esthetic problems for our patients. While conventional
prosthetic treatments offer the best solutions in terms of esthetic result and
durability, they involve the sacrifice of significant quantities of mineralized
dental material and cannot be undertaken before the periodontal tissues are
mature. Other less invasive alternatives should be envisaged as transitional, or
sometimes even permanent, solutions for the management of these anomalies in
children and adolescents. This article discusses these options and presents a
clinical case where composite resin veneers and microabrasion of the enamel were
used to treat dental agenesis and enamel dysplasia.
PMID- 27498053
TI - The neurotrophin receptor p75 mediates gp120-induced loss of synaptic spines in
aging mice.
AB - Human immunodeficiency virus 1 and its envelope protein gp120 reduce
synaptodendritic complexity. However, the mechanisms contributing to this
pathological feature are still not understood. The proneurotrophin brain-derived
neurotrophic factor promotes synaptic simplification through the activation of
the p75 neurotrophin receptor (p75NTR). Here, we have used gp120 transgenic
(gp120tg) mice to investigate whether p75NTR has a role in gp120-mediated
neurotoxicity. Old (~10 months) gp120tg mice exhibited an increase in
proneurotrophin brain-derived neurotrophic factor levels in the hippocampus as
well as a decrease in the number of dendritic spines when compared to age-matched
wild type. These effects were not observed in 3- or 6-month-old mice. To test if
the reduction in spine density and morphology is caused by the activation of
p75NTR, we crossed gp120tg mice with p75NTR null mice. We found that deletion of
only 1 copy of the p75NTR gene in gp120tg mice is sufficient to normalize the
number of hippocampal spines, strongly suggesting that the neurotoxic effect of
gp120 is mediated by p75NTR. These data indicate that p75NTR antagonists could
provide an adjunct therapy against synaptic simplification caused by human
immunodeficiency virus 1.
PMID- 27498054
TI - Preservation of cell-survival mechanisms by the presenilin-1 K239N mutation may
cause its milder clinical phenotype.
AB - Presenilin 1 (PSEN1) mutations are the main cause of monogenic Alzheimer's
disease. We studied the functional effects of the mutation K239N, which shows
incomplete penetrance at the age of 65 years and compared it with the more
aggressive mutation E120G. We engineered stable cell lines expressing human PSEN1
wild type or with K239N or E120G mutations. Both mutations induced dysfunction of
gamma-secretase in the processing of amyloid-beta protein precursor, leading to
an increase in the amyloid beta42/amyloid beta40 ratio. Analysis of homeostatic
mechanisms showed that K239N induced lower basal and hydrogen peroxide induced
intracellular levels of reactive oxygen species than E120G. Similarly, K239N
induced lower vulnerability to apoptosis by hydrogen peroxide injury than E120G.
Accordingly, the proapoptotic signaling pathways c-Jun NH2-terminal kinase and
p38 mitogen-activated protein kinase maintained PSEN1-mediated negative
regulation in K239N but not in E120G-bearing cells. Furthermore, the activation
of the prosurvival signaling pathways mitogen-activated protein
kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/Akt
was lower in E120G-bearing cells. Therefore, preservation of mechanisms
regulating cell responses independent of amyloid-beta protein precursor
processing may account for the milder phenotype induced by the PSEN1 K239N
mutation.
PMID- 27498055
TI - Impact of the high-frequency cutoff of bandpass filtering on ECG quality and
clinical interpretation: A comparison between 40Hz and 150Hz cutoff in a surgical
preoperative adult outpatient population.
AB - BACKGROUND: In 1990 the American Heart Association (AHA) established a standard
0.05 to 150Hz bandwidth for the routine recording of 12-lead electrocardiograms
(ECGs). However, subsequent studies have indicated a very high prevalence of
deviations from the recommended cutoffs. OBJECTIVE: This prospective
observational study investigates the impact of 40Hz compared to 150Hz high
frequency cutoffs on ECG quality and clinical interpretation in a single-center
surgical outpatient population. METHODS: 1582 consecutive adult patients
underwent two standard 12-lead ECG tracings using different high-frequency
cutoffs (40Hz and 150Hz). Two blinded cardiologists randomly reviewed and
interpreted the recordings according to pre-defined parameters (PR and ST
segment, Q and T wave abnormalities). An arbitrary score, ranging from 1 to 3,
was established to evaluate the perceived quality of the recordings and the non
interpretable ECGs were noted. The tracings were then matched to compare
interpretations between 40 and 150Hz filters. RESULTS: A 40Hz high-frequency
cutoff resulted in an increased rate of optimal quality ECGs compared to the
150Hz cutoff (93.4% vs 54.6%; p<0.001) and a lower rate of non-interpretable
traces (0.25% vs 4.80%; p<0.001). Analyzing the morphologic parameters, no
significant differences between the filter settings were found, except for a
higher incidence of the J-point elevation in the 40Hz high-frequency cutoff
(p=0.007) and a higher incidence of left ventricular hypertrophy in the 150Hz
high-frequency cutoff (7.4% vs 5.4%, p<0.001). The latter was noted only in ECGs
with borderline QRS amplitudes (between 3.3 and 3.7mV; p<0.001). CONCLUSION:
Despite current recommendations, the large deviation from standard high-frequency
cutoff in clinical practice does not seem to significantly affect ECG clinical
interpretation and a 40Hz high-frequency cutoff of the band-pass filtering may be
acceptable in a low risk population, allowing for a better quality of tracings.
PMID- 27498056
TI - Endovascular treatment of atherosclerotic popliteal artery disease based on
dynamic angiography findings.
AB - OBJECTIVE: To evaluate efficacy, safety, and midterm patency of endovascular
treatment of obstructive popliteal artery (PA) disease. METHODS: A retrospective
evaluation of patients with atherosclerotic PA disease who underwent percutaneous
transluminal balloon angioplasty and provisional stent, based on both
conventional and dynamic angiographies, was conducted from June 2011 to June
2014. Forty-three patients were included in the study, and most patients had
limited surgical revascularization options. Demographic characteristics,
angiographic findings, interventional data, complications, vessel patency, limb
salvage rates, and survival rates were analyzed. RESULTS: The median lesion
length was 5 cm with 72.1% having total occlusions. The second popliteal segment
(P2) was involved most frequently (60.5%, n = 26). Critical limb ischemia was
present in 69.8%. The technical success rate was 92.9% (42/43 limbs), with 29
cases requiring adjunctive nitinol stents after balloon angioplasty (47.6% based
on conventional angiography, 21.4% based on dynamic angiography, and 4.8%
additional stents based on dynamic angiography). Complications included
thromboembolism (2.3%), perforation (2.3%), pseudoaneurysm (2.3%), and myocardial
infarction (2.3%). Stent fracture was present in three cases (7.1%) during the
mean follow-up period of 18.3 months. The baseline ankle-brachial index
significantly improved after the intervention, from 0.49 +/- 0.11 to 0.92 +/-
0.14 (P < .01). The Rutherford-Becker class decreased from 3.95 +/- 0.76 to 1.76
+/- 0.95 (P < .01) at 12 months. The 1-year primary, primary-assisted, and
secondary patency rates were 75.2% +/- 6.8%, 82.4% +/- 6.0%, and 89.9% +/- 4.8%,
respectively. The limb salvage and amputation-free survival rates at 12 months
were 91.6% and 87.0%, respectively. CONCLUSIONS: Balloon angioplasty with a
provisional stent based on dynamic angiography is a feasible, safe, and effective
therapy for patients with obstructive PA disease. Although the occurrence of
stent fracture is still inevitable, patients with critical limb ischemia who have
limited surgical options may get more benefits from the endovascular treatment of
PA obstructive diseases.
PMID- 27498057
TI - Classifying nonsuicidal overdoses: Nonsuicidal self-injury, suicide attempts, or
neither?
AB - Self-injurious behaviors (SIBs) are leading causes of death and injury.
Unfortunately, disagreement regarding whether and how to classify suicidal and
nonsuicidal SIBs has contributed to their misclassification, likely hindering
clinical care and impeding scientific progress. The present study utilized a data
driven approach to facilitate classification and measurement of three forms of
SIBs, with a particular focus on one with scant clinical and scientific
attention: nonsuicidal overdoses (i.e. intentional overdoses where the person
states that they had no intention of dying from the overdose). Results from this
study demonstrated that nonsuicidal overdoses were similar to suicide attempts in
terms of age of onset, and similar to nonsuicidal self-injury (NSSI) in terms of
suicidal thoughts and desire to die when engaging in these behaviors. Nonsuicidal
overdoses were unique from NSSI and suicide attempts in terms of the reported
likelihood of dying from the behavior. The present study highlighted that current
definitions for nonsuicidal behaviors (including requirements that the person has
zero intent to die) may not accurately represent people's intent when engaging in
these behaviors. Additionally, the present study highlighted that empirical
analysis of SIBs can provide important insights for classification of SIBs.
PMID- 27498058
TI - Retrieval and classification of food images.
AB - Automatic food understanding from images is an interesting challenge with
applications in different domains. In particular, food intake monitoring is
becoming more and more important because of the key role that it plays in health
and market economies. In this paper, we address the study of food image
processing from the perspective of Computer Vision. As first contribution we
present a survey of the studies in the context of food image processing from the
early attempts to the current state-of-the-art methods. Since retrieval and
classification engines able to work on food images are required to build
automatic systems for diet monitoring (e.g., to be embedded in wearable cameras),
we focus our attention on the aspect of the representation of the food images
because it plays a fundamental role in the understanding engines. The food
retrieval and classification is a challenging task since the food presents high
variableness and an intrinsic deformability. To properly study the peculiarities
of different image representations we propose the UNICT-FD1200 dataset. It was
composed of 4754 food images of 1200 distinct dishes acquired during real meals.
Each food plate is acquired multiple times and the overall dataset presents both
geometric and photometric variabilities. The images of the dataset have been
manually labeled considering 8 categories: Appetizer, Main Course, Second Course,
Single Course, Side Dish, Dessert, Breakfast, Fruit. We have performed tests
employing different representations of the state-of-the-art to assess the related
performances on the UNICT-FD1200 dataset. Finally, we propose a new
representation based on the perceptual concept of Anti-Textons which is able to
encode spatial information between Textons outperforming other representations in
the context of food retrieval and Classification.
PMID- 27498059
TI - Sclerostin expression in skeletal sarcomas.
AB - Sclerostin (SOST) is an extracellular Wnt signaling antagonist which negatively
regulates bone mass. Despite this, the expression and function of SOST in
skeletal tumors remain poorly described. Here, we first describe the
immunohistochemical staining pattern of SOST across benign and malignant skeletal
tumors with bone or cartilage matrix (n=68 primary tumors). Next, relative SOST
expression was compared to markers of Wnt signaling activity and osteogenic
differentiation across human osteosarcoma (OS) cell lines (n=7 cell lines
examined). Results showed immunohistochemical detection of SOST in most bone
forming tumors (90.2%; 46/51) and all cartilage-forming tumors (100%; 17/17).
Among OSs, variable intensity and distribution of SOST expression were observed,
which highly correlated with the presence and degree of neoplastic bone. Patchy
SOST expression was observed in cartilage-forming tumors, which did not
distinguish between benign and malignant tumors or correlate with regional
morphologic characteristics. Finally, SOST expression varied widely between OS
cell lines, with more than 97-fold variation. Among OS cell lines, SOST
expression positively correlated with the marker of osteogenic differentiation
alkaline phosphatase and did not correlate well with markers of Wnt/beta-catenin
signaling activity. In summary, SOST is frequently expressed in skeletal bone-
and cartilage-forming tumors. The strong spatial correlation with bone formation
and the in vitro expression patterns are in line with the known functions of SOST
in nonneoplastic bone, as a feedback inhibitor on osteogenic differentiation.
With anti-SOST as a potential therapy for osteoporosis in the near future, its
basic biologic and phenotypic consequences in skeletal tumors should not be
overlooked.
PMID- 27498060
TI - Overexpression of DIXDC1 correlates with enhanced cell growth and poor prognosis
in human pancreatic ductal adenocarcinoma.
AB - Disheveled-axin (DIX) domain containing 1 (DIXDC1), a protein containing a coiled
coil domain and a DIX domain, is involved in the progression of multiple cancers.
However, the role of DIXDC1 in human pancreatic ductal adenocarcinoma (PDAC)
remains unclear. In this study, we investigated the role and prognostic value of
DIXDC1 in the development of human PDAC. Western blot analysis revealed that
DIXDC1 was highly expressed in PDAC tissues and cell lines. Immunohistochemistry
on 165 paraffin-embedded sections showed that high expression of DIXDC1 was
significantly correlated with tumor size (P = .002), histological differentiation
(P = .001), tumor node metastasis (TNM) stage (P = .001), and the proliferation
marker Ki-67 (P = .000). Importantly, Kaplan-Meier analysis revealed that high
expression of DIXDC1 was obviously correlated with worsened overall survival (P <
.001). In vitro, using serum starvation-refeeding experiments, our results
suggested that DIXDC1 was up-regulated in proliferating PDAC cells, together with
the percentage of cells at the S phase, and was correlated with the expression of
cyclin D1. In addition, depletion of DIXDC1 decreased PCNA and cyclin D1 levels.
Accordingly, CCK-8, colony formation, and flow cytometry analyses revealed that
knocking down DIXDC1 induced growth impairment and G1/S cell cycle arrest in PDAC
cells, while overexpression of DIXDC1 led to accelerated cell proliferation and
cell cycle progression. On the basis of these results, we propose that DIXDC1
could play an important role in the tumorigenesis of PDAC and serve as a
potential therapeutical target to prevent PDAC progression.
PMID- 27498061
TI - Characterization of the leiomyomatous variant of myofibroblastoma: a rare subset
distinct from other smooth muscle tumors of the breast.
AB - Mammary myofibroblastoma is a benign spindle cell tumor that can show variable
morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a
family of CD34-positive tumors with similar morphology that show a deletion of
13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates
distinct smooth muscle differentiation. We aimed to characterize 4 cases of the
leiomyomatous variant of myofibroblastoma arising in the breast by
clinicopathological, immunohistochemical, and molecular means. All 4 examples
arose in women aged 41 to 62 years (median, 46.5 years). Tumors ranged in size
from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were
characterized by bundles of smooth muscle cells with elongated cigar-shaped
nuclei and eosinophilic cytoplasm. All 4 tumors showed diffuse positive staining
with desmin, caldesmon, smooth muscle actin, estrogen receptor, and Bcl-2. CD34
staining was diffusely positive in 2 cases, was weak and patchy in 1 case, and
was negative in 1 case. Two (50%) of 4 tumors showed deletion of RB1 by
fluorescence in situ hybridization. Loss of Rb staining was seen in 1 tumor with
RB1 deletion by fluorescence in situ hybridization, whereas intact Rb staining
was observed in 1 nondeleted case studied. In conclusion, this rare variant of
myofibroblastoma is a distinct subgroup of tumors among an already uncommon
category of (smooth muscle) breast tumors. Some reported examples of "parenchymal
leiomyoma" may represent the leiomyomatous variant of myofibroblastoma.
PMID- 27498062
TI - Renal oncocytoma with vascular invasion: a series of 22 cases.
AB - Renal oncocytomas are benign neoplasms that are often excised, as clinically they
cannot be distinguished with certainty from renal cell carcinoma. One of the
least common findings in oncocytomas is vascular invasion, and their behavior is
not well characterized with only reports of isolated examples and smaller case
series. Whether vascular invasion is acceptable for the diagnosis of oncocytoma
still remains controversial, even amongst genitourinary pathologists with
expertise in renal tumor pathology. Of 1474 cases of renal oncocytoma identified
at 3 large medical centers, 22 (1.5%) had vascular invasion. Patients included 12
men and 10 women with an average age at diagnosis of 67.5 years (range, 48-91
years). Thirteen cases showed large vessel invasion, and the remainder involved
medium or small vessels. Tumor was grossly visible in the renal vein in 2 cases.
Clinical data were available on 16 of the 22 cases with an average follow-up time
of 29.9 months (range, 7.5-94.5 months). Of the cases with clinical follow-up,
all but one individual was alive. All living individuals were free of recurrence
or metastatic disease at the time of last follow-up. Our cohort showed no
metastasis or recurrence and overall survival of 94.7% at 2.5 years following
diagnosis, supporting the finding that vascular invasion does not alter the
favorable prognosis of oncocytoma. The presence of vascular invasion should not
lead to any uncertainty about the diagnosis in an otherwise typical oncocytoma.
PMID- 27498063
TI - Collagen type III alpha1 as a useful diagnostic immunohistochemical marker for
fibroepithelial lesions of the breast.
AB - Phyllodes tumors (PTs) of the breast constitute an uncommon group of
fibroepithelial neoplasms that are classified into benign, borderline, and
malignant categories based on a constellation of histologic characteristics
including cytologic atypia, mitotic count, degree of stromal cellularity, stromal
overgrowth, and microscopic margins. Accurately and reproducibly differentiating
these tumors is a long-standing diagnostic challenge. In addition, the
distinction between benign PT from cellular fibroadenoma (FA) is especially
difficult because of overlapping microscopic features. We have previously shown
differential expression of various collagens, including collagen type III alpha1
(Col3A) in breast carcinomas. In this study, we evaluated clinicopathological
characteristics of 95 cases of fibroepithelial lesions including 56 PTs and 39
FAs (25 cellular FA, 14 typical FA) and correlated them with the
immunohistochemical staining pattern for Col3A. We found that stromal Col3A
expression was significantly increased in PTs when compared with FAs (P < .0001).
Among the PT groups, there was significantly increased expression from benign
tumors through borderline to malignant tumors. High Col3A expression was
associated with PT type, irregular margin status, and high mitotic activity. A
distinct periductal cuffing pattern of Col3A staining was unique to PTs and
absent in FAs. These findings suggest that Col3A can be a potential adjunct
marker for both differentiating FA from PT and assessing malignant potential in
PTs.
PMID- 27498064
TI - Defining a new aggressiveness classification and using NFATc1 localization as a
prognostic factor in cherubism.
AB - Cherubism is a rare genetic disease characterized by bilateral giant cell
reparative granuloma of the jaws consisting of a fibrotic stroma with giant
multinucleated cells (GMCs) and osteoclastic features. Cherubism severity is
highly variable, and recurrence after surgery is the most important risk.
Currently, there are no prognostic indicators. The aims of this study were to
evaluate the osteoclastogenesis phenotype by histologic examination of nuclear
factor of activated T cells 1 (NFATc1) localization and tartrate-resistant acid
phosphatase (TRAP) activity and to correlate the results to disease
aggressiveness to define prognostic indicators. Based on cherubism evolution 1
year after surgery, 3 classes of cherubism aggressiveness were identified: mild
(group A), moderate (group B), and severe (group C). Histologically, in grade A
and B cherubism lesions, GMCs were negative for both TRAP activity and NFATc1
nuclear localization. In contrast, in grade C cherubism lesions, GMCs were all
positive for TRAP activity and NFATc1 nuclear localization and displayed
osteoclast-like features. Other histopathologic findings were not different among
the 3 groups. Our results establish that TRAP activity and NFTAc1 nuclear
localization are associated with aggressive cherubism and therefore could be
added to routine pathologic examination to aid in prognosis and management of the
disease. The finding of NFATc1 nuclear localization in aggressive tumors supports
the addition of anticalcineurin treatment to the therapeutic arsenal for
cherubism.
PMID- 27498065
TI - Influence of the sickness benefit reform on sickness absence.
AB - OBJECTIVES: To analyse short-term changes in sick-leave use after the
implementation of sick-pay cut policy in Estonia on July 1, 2009. METHODS: The
study is based on all sick-leave episodes of 20-64-year-old employees registered
by the Estonian Health Insurance Fund in 2008 and 2011, which covers 227,981
persons in 2008 and 152,102 persons in 2011. Population- and absentee-level
sickness absence measures were used to describe sickness absence. Multiple
logistic regression analysis was performed to explore associations between sick
pay cut and sickness absence measures. RESULTS: The main impact of the reform was
that the total number of sick-leave episodes and sick-listed persons decreased by
one third. The number of sick leave episodes lasting 4-20days decreased by half
whereas the change in shorter and longer episodes was negligible. Chances of
recurrent sick-leave lowered significantly. The mean duration of sick-leave
episodes lengthened in a positive correlation with age. CONCLUSION: At the
population level sickness absence decreased after the sick-pay cut, which was one
of the goals of the reform. The sickness absence of absentees with long-lasting
illnesses did not change, but people with shorter illnesses adapted their
sickness absence behaviour. It indicates that health outcomes of people whose
absence has decreased due to policy changes need to be followed.
PMID- 27498067
TI - Computing disease incidence, prevalence and comorbidity from electronic medical
records.
AB - Electronic medical records (EMR) represent a convenient source of coded medical
data, but disease patterns found in EMRs may be biased when compared to surveys
based on sampling. In this communication we draw attention to complications that
arise when using EMR data to calculate disease prevalence, incidence, age of
onset, and disease comorbidity. We review known solutions to these problems and
identify challenges for future work.
PMID- 27498066
TI - Let's get Physiqual - An intuitive and generic method to combine sensor
technology with ecological momentary assessments.
AB - The emergence of wearables and smartwatches is making sensors a ubiquitous
technology to measure daily rhythms in physiological measures, such as movement
and heart rate. An integration of sensor data from wearables and self-report
questionnaire data about cognition, behaviors, and emotions can provide new
insights into the interaction of mental and physiological processes in daily
life. Hitherto no method existed that enables an easy-to-use integration of
sensor and self-report data. To fill this gap, we present 'Physiqual', a platform
for researchers that gathers and integrates data from commercially available
sensors and service providers into one unified format for use in Ecological
Momentary Assessments (EMA) or Experience Sampling Methods (ESM), and Quantified
Self (QS). Physiqual currently supports sensor data provided by two well-known
service providers and therewith a wide range of smartwatches and wearables. To
demonstrate the features of Physiqual, we conducted a case study in which we
assessed two subjects by means of data from an EMA study combined with sensor
data as aggregated and exported by Physiqual. To the best of our knowledge, the
Physiqual platform is the first platform that allows researchers to conveniently
aggregate and integrate physiological sensor data with EMA studies.
PMID- 27498068
TI - Boosting backpropagation algorithm by stimulus-sampling: Application in computer
aided medical diagnosis.
AB - Neural networks (NNs), in general, and multi-layer perceptron (MLP), in
particular, represent one of the most efficient classifiers among the machine
learning (ML) algorithms. Inspired by the stimulus-sampling paradigm, it is
plausible to assume that the association of stimuli with the neurons in the
output layer of a MLP can increase its performance. The stimulus-sampling process
is assumed memoryless (Markovian), in the sense that the choice of a particular
stimulus at a certain step, conditioned by the whole prior evolution of the
learning process, depends only on the network's answer at the previous step. This
paper proposes a novel learning technique, by enhancing the standard
backpropagation algorithm performance with the aid of a stimulus-sampling
procedure applied to the output neurons. The network uses the observable behavior
that varies throughout the training process by stimulating the correct answers
through corresponding rewards/penalties assigned to the output neurons. The
proposed model has been applied in computer-aided medical diagnosis using five
real-life breast cancer, colon cancer, diabetes, thyroid, and fetal heartbeat
databases. The statistical comparison to well-established ML algorithms proved
beyond doubt its efficiency and robustness.
PMID- 27498069
TI - A vision based proposal for classification of normal and abnormal gait using RGB
camera.
AB - Human gait is mainly related to the foot and leg movements but, obviously, the
entire motor system of the human body is involved. We hypothesise that movement
parameters such as dynamic balance, movement harmony of each body element (arms,
head, thorax...) could enable us to finely characterise gait singularities to
pinpoint potential diseases or abnormalities in advance. Since this paper deals
with the preliminary problem pertaining to the classification of normal and
abnormal gait, our study will revolve around the lower part of the body. Our
proposal presents a functional specification of gait in which only observational
kinematic aspects are discussed. The resultant specification will confidently be
open enough to be applied to a variety of gait analysis problems encountered in
areas connected to rehabilitation, sports, children's motor skills, and so on. To
carry out our functional specification, we develop an extraction system through
which we analyse image sequences to identify gait features. Our prototype not
only readily lets us determine the dynamic parameters (heel strike, toe off,
stride length and time) and some skeleton joints but also satisfactorily supplies
us with a proper distinction between normal and abnormal gait. We have performed
experiments on a dataset of 30 samples.
PMID- 27498070
TI - Optical discrimination of benign and malignant oral tissue using Z-scan
technique.
AB - A new optical method to discriminate benign and malignant oral tissue is
reported. Twenty four tissue biopsy of patients tumor have been prepared in
standard method without coloring process. The CW He-Ne laser beam interrogated
the samples in optical setup. Linear absorption of tissues in laser wavelength
measured and nonlinear behavior of tissue biopsies has been investigated by Z
scan setup. We used some simple optical instruments to focus on microsize region
of biolayer to investigate less number of cells and to take repeatable test.
Results show that the malignant samples have more attenuation than benign
samples. Furthermore nonlinear refractive index (n2) of malignant biolayers has
positive sign and n2 of benign biopsies has negative sign with the 10-8(cm2/W)
order of magnitude. So this optical method may be used to discriminate malignant
from benign tissues.
PMID- 27498071
TI - Expression of the K+/Cl- cotransporter, KCC2, in cerebellar Purkinje cells is
regulated by group-I metabotropic glutamate receptors.
AB - The neuronal K+/Cl- symporter, KCC2, shapes synaptic responses mediated by Cl-
permeant GABAA receptors. Moving from the evidence that excitatory
neurotransmission drives changes in KCC2 expression in cerebellar neurons, we
studied the regulation of KCC2 expression by group-I metabotropic glutamate
(mGlu) receptors in the cerebellum of adult mice. Mice lacking mGlu5 receptors
showed a large reduction in cerebellar KCC2 protein levels and a loss of KCC2
immunoreactivity in Purkinje cells. Similar changes were seen in mice treated
with the mGlu5 receptor antagonist, MPEP, whereas treatment with the mGlu5
receptor positive allosteric modulator (PAM), VU0360172, increased KCC2
expression. In contrast, pharmacological inhibition of mGlu1 receptors with
JNJ16259685 enhanced cerebellar KCC2 protein levels and KCC2 immunoreactivity in
Purkinje cells, whereas treatment with the mGlu1 receptor PAM, RO0711401, reduced
KCC2 expression. To examine whether the reduction in KCC2 expression caused by
the absence or the inhibition of mGlu5 receptors could affect GABAergic
transmission, we performed electrophysiological and behavioral studies. Recording
of extracellular action potentials in Purkinje cells showed that the inhibitory
effect of the GABAA receptor agonist, muscimol, was lost in cerebellar slices
prepared from mGlu5-/- mice or from mice treated systemically with MPEP, in line
with the reduction in KCC2 expression. Similarly, motor impairment caused by the
GABAA receptor PAM, diazepam, was attenuated in mice pre-treated with MPEP. These
findings disclose a novel function of mGlu5 receptors in the cerebellum and
suggest that mGlu5 receptor ligands might influence GABAergic transmission in the
cerebellum and affect motor responses to GABA-mimetic drugs. This article is part
of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.
PMID- 27498072
TI - Impact of baseline body mass index status on glucose lowering and weight change
during sitagliptin treatment for type 2 diabetics.
AB - AIMS: This study was designed to evaluate the efficacy of sitagliptin in
Taiwanese diabetic subjects with different baseline BMI status. METHODS: This was
a single-center, hospital-based, retrospective chart review in subjects (n=1874)
with type 2 diabetes who received sitagliptin. Subjects were classified into
subgroups depending upon their baseline BMI by Taiwan national weight
classification: normal (BMI<24kg/m(2)) (n=504), overweight (BMI: 24-27kg/m(2))
(n=615), and obese (BMI?27kg/m(2)) (n=755). Changes in HbA1c and weight were
evaluated over a 12month treatment period. RESULTS: For all three groups, the
HbA1c levels declined over the first three months by about 8%, and subsequently
plateaued for the next nine months. Obese subjects were slower in reducing HbA1c
compared with normal and overweight subjects (P<0.05), but at nine months the
reduction was similar across groups. Mean body weight increased over the first
nine months of sitagliptin therapy in subjects with normal BMI (57.12-58.30kg),
but there was no change in mean body weight in the overweight group. After three
months the obese groups had significantly greater loss in body weight compared
with the normal group. CONCLUSIONS: Baseline BMI status may influence the
reduction of HbA1c levels within the first six months of sitagliptin therapy and
affect weight change after three months. Being obese was associated with an
initial lag in HbA1c reduction and greater weight loss compared with normal and
overweight subjects.
PMID- 27498073
TI - Effects of delay and probability combinations on discounting in humans.
AB - To determine discount rates, researchers typically adjust the amount of an
immediate or certain option relative to a delayed or uncertain option. Because
this adjusting amount method can be relatively time consuming, researchers have
developed more efficient procedures. One such procedure is a 5-trial adjusting
delay procedure, which measures the delay at which an amount of money loses half
of its value (e.g., $1000 is valued at $500 with a 10-year delay to its receipt).
Experiment 1 (n=212) used 5-trial adjusting delay or probability tasks to measure
delay discounting of losses, probabilistic gains, and probabilistic losses.
Experiment 2 (n=98) assessed combined probabilistic and delayed alternatives. In
both experiments, we compared results from 5-trial adjusting delay or probability
tasks to traditional adjusting amount procedures. Results suggest both procedures
produced similar rates of probability and delay discounting in six out of seven
comparisons. A magnitude effect consistent with previous research was observed
for probabilistic gains and losses, but not for delayed losses. Results also
suggest that delay and probability interact to determine the value of money. Five
trial methods may allow researchers to assess discounting more efficiently as
well as study more complex choice scenarios.
PMID- 27498075
TI - Sofosbuvir plus daclatasvir with or without ribavirin for chronic hepatitis C
infection: Impact of drug concentration on viral load decay.
AB - BACKGROUND: Sofosbuvir (SOF) plus daclatasvir (DCV) with or without ribavirin is
one of the currently recommended treatment option for chronic hepatitis C. AIMS:
Our objectives were to identify factors associated with SOF/DCV plasma
concentrations [C] variations and to evaluate their impact on viral kinetics.
METHODS: 130 consecutive HCV patients initiating SOF/DCV therapy with or without
ribavirin were enrolled. Clinical, biological, virological and pharmacological
data were collected at baseline, at week 4, 8, 12, and 24 of therapy and 12 weeks
after the end of therapy. RESULTS: Mean age was 57 years, 68% of patients were
males, 69% were infected by HCV genotype 1 and cirrhosis was observed in 76% of
patients. Multivariate analysis showed that higher SOF [C] and DCV [C] during
treatment were associated with eGFR impairment and absence of cirrhosis. We found
a significant correlation between the magnitude of HCV viral load decrease from
day 0 to week 4 and a higher SOF [C] at week 4 (p=0.032) and a higher DCV [C] at
week 8 (p=0.013). CONCLUSIONS: Pharmacological monitoring showed significant
associations between elevated SOF or DCV [C] and absence of cirrhosis, decreased
eGFR and viral load decrease during the first month of treatment.
PMID- 27498074
TI - Missed treatment in an Italian HBV infected patients cohort: HBV RER.
AB - BACKGROUND AND AIMS: Very little is known about the access to treatment for
Chronic Hepatitis B in the real clinical practice and the characteristics of the
patients who do not receive antiviral therapy. METHODS: HBV-RER is an
observational multicenter network that collected data of patients with HBV
infection during a 3 years observational period (2009-2012). RESULTS: Among 2527
HBsAg positive patients, 1099 were never treated (NT); only 280 were included in
the analysis due to different exclusion causes A minority was HBeAg-positive. The
median age was 42. At liver biopsy most patients had Metavir score of F0-F1.
Univariate analysis between 280 NT patients and the 290 naive to treatment showed
that NT patients were mostly female (P=0.002), not Italian (P=0.044), younger
(P<0.001). Metavir score was lower in NT (P0.002), such as the Fib4 score
(P<0.001). HBV DNA level was significantly higher in NT. At multivariate
analysis, independent variables associated with no-treatment were younger age,
female gender, Metavir score F0-F1, Fib4 lower than 1.6 and lower blood level of
HBV-DNA. CONCLUSIONS: There is a large number of patients eligible to treatment
who do not receive it. A younger age and a less severe disease seem to be
associated to deferral of treatment.
PMID- 27498076
TI - Inhibition of late sodium current attenuates ionic arrhythmia mechanism in
ventricular myocytes expressing LaminA-N195K mutation.
AB - BACKGROUND: Lamin A and C are nuclear filament proteins encoded by the LMNA gene.
Mutations in the LMNA gene cause many congenital diseases known as laminopathies,
including Emery-Dreifuss muscular dystrophy, Hutchinson-Gilford progeria
syndrome, and familial dilated cardiomyopathy (DCM) with conduction disease. A
missense mutation (N195K) in the A-type lamins results in familial DCM and sudden
arrhythmic death. OBJECTIVE: The purpose of this study was to investigate the ion
current mechanism of arrhythmia and DCM caused by the LaminA-N195K variant.
METHODS: A homozygous mouse line expressing the Lmna-N195K mutation
(LmnaN195K/N195K) that exhibited arrhythmia, DCM, and sudden death was used.
Using whole cell patch-clamp technique, we measured action potential duration
(APD), Na+ currents (INa) in ventricular myocytes isolated from LmnaN195K/N195K,
and wild-type mice. RESULTS: Both peak and late INa were significantly (P <.05)
increased in LmnaN195K/N195K ventricular myocytes. Similarly, LmnaN195K/N195K
ventricular myocytes exhibited significant (P <.005) prolongation of APD (time to
50% [APD50] and 90% [APD90] repolarization) and triggered activity. Acute
application of ranolazine inhibited late INa, shortened APD, and abolished
triggered activity in LmnaN195K/N195K ventricular myocytes. CONCLUSION:
Inhibition of late INa may be an effective therapy in preventing arrhythmia in
patients with LmnaN195K mutation-related DCM.
PMID- 27498077
TI - Risk stratification in Brugada syndrome: Where is the finish line?
PMID- 27498078
TI - The search for links between atrial fibrillation pathogenesis and ablation
outcomes.
PMID- 27498079
TI - Synchronous ventricular pacing with direct capture of the atrioventricular
conduction system: Functional anatomy, terminology, and challenges.
AB - Right ventricular apical pacing is associated with an increased incidence of
heart failure, atrial fibrillation, and overall mortality. As a result, pacing
the ventricles in a manner that closely mimics normal AV conduction with an
intact His-Purkinje system has been explored. Recently, the sustainable benefits
of selective His-bundle stimulation have been demonstrated and proposed as the
preferred method of ventricular stimulation for appropriate patients. Ideally,
conduction system pacing should be selective without myocardial capture, overcome
distal bundle branch block when present, and not compromise tricuspid valve
function. Contemporary literature on conduction system pacing is confusing
largely because of inconsistent terminology and, at times, anatomically
inaccurate terms used interchangeably for nonsynonymous anatomic sites. In this
review, we discuss the functional anatomy of AV conduction access with specific
emphasis on terminology, relationship to the membranous septum, tricuspid valve
tissue, and proximity to atrial or ventricular myocardium. The potential benefits
of each specific site as well as associated unique difficulties with those sites
are described.
PMID- 27498080
TI - Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2
trial.
AB - BACKGROUND: A subset of patients with metastatic renal-cell carcinoma show
indolent growth of metastases. Because of the toxicity and non-curative nature of
systemic therapy, some of these patients could benefit from initial active
surveillance. We aimed to characterise the time to initiation of systemic therapy
in patients with metastatic renal-cell carcinoma under active surveillance.
METHODS: In this prospective phase 2 trial, we enrolled patients with treatment
naive, asymptomatic, metastatic renal-cell carcinoma from five hospitals in the
USA, Spain, and the UK. Patients were radiographically assessed at baseline,
every 3 months for year 1, every 4 months for year 2, then every 6 months
thereafter. Patients continued on observation until initiation of systemic
therapy for metastatic renal-cell carcinoma; a decision that was made at the
discretion of the treating physician and patient. The primary endpoint of the
study was time to initiation of systemic therapy in the per-protocol population.
The follow-up of patients is ongoing. FINDINGS: Between Aug 21, 2008, and June 7,
2013, we enrolled 52 patients. Median follow-up of patients in the study was 38.1
months (IQR 29.4-48.9). In the 48 patients included in analysis, median time on
surveillance from registration on study until initiation of systemic therapy was
14.9 months (95% CI 10.6-25.0). Multivariate analysis showed that higher numbers
of International Metastatic Database Consortium (IMDC) adverse risk factors
(p=0.0403) and higher numbers of metastatic disease sites (p=0.0414) were
associated with a shorter surveillance period. 22 (46%) patients died during the
study period, all from metastatic renal-cell carcinoma. INTERPRETATION: A subset
of patients with metastatic renal-cell carcinoma can safely undergo surveillance
before starting systemic therapy. Additional investigation is required to further
define the benefits and risks of this approach. FUNDING: None.
PMID- 27498081
TI - Delayed systemic treatment in metastatic renal-cell carcinoma.
PMID- 27498082
TI - Tools for opening new chapters in the book of Treponema pallidum evolutionary
history.
AB - Treponema pallidum infections causing yaws disease and venereal syphilis are
globally widespread in human populations, infecting hundreds of thousands and
millions annually respectively; endemic syphilis is much less common, and pinta
has not been observed in decades. We discuss controversy surrounding the origin,
evolution and history of these pathogens in light of available molecular and
anthropological evidence. These bacteria (or close relatives) seem to affect many
wild African nonhuman primate (NHP) species, though to date only a single NHP
Treponema pallidum genome has been published, hindering detection of spillover
events and our understanding of potential wildlife reservoirs. Similarly, only
ten genomes of Treponema pallidum infecting humans have been published, impeding
a full understanding of their diversity and evolutionary history. Research
efforts have been hampered by the difficulty of culturing and propagating
Treponema pallidum. Here we highlight avenues of research recently opened by the
coupling of hybridization capture and next-generation sequencing. We present data
generated with such an approach suggesting that asymptomatic bones from NHP
occasionally contain enough treponemal DNA to recover large fractions of their
genomes. We expect that these methods, which naturally can be applied to modern
biopsy samples and ancient human bones, will soon considerably improve our
understanding of these enigmatic pathogens and lay rest to old yet unresolved
controversies.
PMID- 27498083
TI - Event-related potentials and cognition in Parkinson's disease: An integrative
review.
AB - Cognitive impairment is a common non-motor symptom of Parkinson's disease (PD),
but the nature of cognitive changes varies considerably between individuals.
According to the dual-syndrome hypothesis, one cluster of patients is
characterized by deficits in executive function that may be related to fronto
striatal dysfunction. Other patients primarily show non-frontal cognitive
impairments that progress rapidly to PD dementia (PDD). We provide a
comprehensive review of event-related potential (ERP) studies to identify ERP
measures substantiating the heterogeneity of cognitive impairment in PD. Our
review revealed evidence for P3b and mismatch-negativity alterations in PDD, but
not in non-demented PD, indicating that alterations of these ERPs constitute
electrophysiological markers for PDD. In contrast, ERP correlates of executive
functions, such as NoGo-P3, N2, and error(-related) negativity (Ne/ERN), appear
to be attenuated in non-demented PD patients in a dopamine-dependent manner.
Hence, ERP measures confirm and yield distinct electrophysiological markers for
the heterogeneity of cognitive impairment in PD. We discuss limitations and open
questions of the ERP approach and provide directions and predictions for future
ERP research.
PMID- 27498085
TI - Effects of combining ozone and hydrogren peroxide on tooth bleaching: A clinical
study.
AB - OBJECTIVES: The purpose of this study was to evaluate the efficiency of bleaching
after combining ozone and 38% H2O2 in comparison to the sole use of 38% H2O2.
METHODS: Consecutive 26 participants (13 males and 13 females) were recruited
into this study. They were randomly allocated into 2 groups (n=13 for each
group). In group 1 (test group); the participants' upper anterior teeth were
treated with 38% H2O2 for 20min then the teeth were exposed to ozone for 60s
(healOzone((r)) X4, KaVo Dental, Biberach, Germany). In group 2 (controls); the
upper anterior teeth were treated with 20min of 38% H2O2 only. The shade of teeth
was evaluated by recording the L* a* b* values and Vita Classic shades at study
baseline and after bleaching in both groups. The statistically significant
changes were set at P<=0.05. RESULTS: Tooth sensitivity and teeth shades were
comparable between groups at study baseline (p>0.05). Controls reported more
tooth sensitivity following bleaching (p<0.001). Teeth achieved better Vita
shades, higher L* values (lighter shades), and lower a* and b* values (lighter
shades) after bleaching in both groups (P<=0.05). However, teeth bleached with
H2O2 and ozone achieved better Vita shades, higher L* values and lower a* values
(lighter shades) than those bleached with H2O2 alone (p<0.001). Changes in b*
values were not significantly different between groups. CONCLUSIONS: Bleaching
with 38% H2O2 for 20min followed by 60s of ozone application would result in
teeth with lighter shades than bleaching with 38% H2O2 alone.
PMID- 27498084
TI - Sex differences in brain and behavior in adolescence: Findings from the
Philadelphia Neurodevelopmental Cohort.
AB - Sex differences in brain and behavior were investigated across the lifespan.
Parameters include neurobehavioral measures linkable to neuroanatomic and
neurophysiologic indicators of brain structure and function. Sexual
differentiation of behavior has been related to organizational factors during
sensitive periods of development, with adolescence and puberty gaining increased
attention. Adolescence is a critical developmental period where transition to
adulthood is impacted by multiple factors that can enhance vulnerability to brain
dysfunction. Here we highlight sex differences in neurobehavioral measures in
adolescence that are linked to brain function. We summarize neuroimaging studies
examining brain structure, connectivity and perfusion, underscoring the
relationship to sex differences in behavioral measures and commenting on hormonal
findings. We focus on relevant data from the Philadelphia Neurodevelopmental
Cohort (PNC), a community-based sample of nearly 10,000 clinically and
neurocognitively phenotyped youths age 8-21 of whom 1600 have received multimodal
neuroimaging. These data indicate early and pervasive sexual differentiation in
neurocognitive measures that is linkable to brain parameters. We conclude by
describing possible clinical implications.
PMID- 27498086
TI - Structural biology of glucan phosphatases from humans to plants.
AB - Glucan phosphatases are functionally conserved at the enzymatic level,
dephosphorylating glycogen in animals and starch in plants. The human glucan
phosphatase laforin is the founding member of the family and it is comprised of a
carbohydrate binding module (CBM) domain followed by a dual specificity
phosphatase (DSP) domain. Plants encode two glucan phosphatases: Starch EXcess4
(SEX4) and Like Sex Four2 (LSF2). SEX4 contains a DSP domain followed by a CBM
domain, while LSF2 contains a DSP domain and lacks a CBM. This review
demonstrates how glucan phosphatase function is conserved and highlights how each
family member employs a unique mechanism to bind and dephosphorylate glucan
substrates.
PMID- 27498087
TI - The endothelial E3 ligase HECW2 promotes endothelial cell junctions by increasing
AMOTL1 protein stability via K63-linked ubiquitination.
AB - Cell-to-cell junctions are critical for the formation of endothelial barriers,
and its disorganization is required for sprouting angiogenesis. Members of the
angiomotin (AMOT) family have emerged as key regulators in the control of
endothelial cell (EC) junction stability and permeability. However, the
underlying mechanism by which the AMOT family is regulated in ECs remains
unclear. Here we report that HECW2, a novel EC ubiquitin E3 ligase, plays a
critical role in stabilizing endothelial cell-to-cell junctions by regulating
AMOT-like 1 (AMOTL1) stability. HECW2 physically interacts with AMOTL1 and
enhances its stability via lysine 63-linked ubiquitination. HECW2 depletion in
human ECs decreases AMOTL1 stability, loosening the cell-to-cell junctions and
altering subcellular localization of yes-associated protein (YAP) from cytoplasm
into the nucleus. Knockdown of HECW2 also results in increased angiogenic
sprouting, and this effect is blocked by depletion of ANG-2, a potential target
of YAP. These results demonstrate that HECW2 is a novel regulator of angiogenesis
and provide new insights into the mechanisms coordinating junction stability and
angiogenic activation in ECs.
PMID- 27498088
TI - Nonstatins and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors:
Role in Non-Familial Hypercholesterolemia.
AB - After maximizing statin and lifestyle adherence, some patients may benefit from
additional low-density lipoprotein cholesterol (LDL-C) lowering. The potential
for net benefit from added therapy can inform nonstatin decision-making.
Considering patient risk and the LDL-C level on statin, the additional potential
cardiovascular disease (CVD) risk reduction benefit from further lowering LDL-C
depends on the magnitude of LDL-C lowering from the nonstatin. Ezetimibe is the
only nonstatin shown to reduce atherosclerotic CVD events added to a statin,
albeit modestly, since it modestly reduces LDL-C by about 20%. Proprotein
Convertase Subtilisin-Like/Kexin Type 9 mononclonal antibodies lower LDL-Cby 45
65%, but definitive CVD outcomes and safety trials are pending. Niacin and
fenofibrate do not clearly reduce CVD events in statin-treated patients, and may
increase adverse events. Bile acid sequestrants have not been evaluated in CVD
outcome trials in statin-treated patients, and have an excess of adverse effects.
Cost also plays a role in access to nonstatin therapy. These considerations may
inform shared decision-making.
PMID- 27498089
TI - A discriminative feature selection approach for shape analysis: Application to
fetal brain cortical folding.
AB - The development of post-processing reconstruction techniques has opened new
possibilities for the study of in-utero fetal brain MRI data. Recent cortical
surface analysis have led to the computation of quantitative maps characterizing
brain folding of the developing brain. In this paper, we describe a novel feature
selection-based approach that is used to extract the most discriminative and
sparse set of features of a given dataset. The proposed method is used to
sparsely characterize cortical folding patterns of an in-utero fetal MR dataset,
labeled with heterogeneous gestational age ranging from 26 weeks to 34 weeks. The
proposed algorithm is validated on a synthetic dataset with both linear and non
linear dynamics, supporting its ability to capture deformation patterns across
the dataset within only a few features. Results on the fetal brain dataset show
that the temporal process of cortical folding related to brain maturation can be
characterized by a very small set of points, located in anatomical regions
changing across time. Quantitative measurements of growth against time are
extracted from the set selected features to compare multiple brain regions (e.g.
lobes and hemispheres) during the considered period of gestation.
PMID- 27498090
TI - A novel thiol-affinity micropipette tip method using zinc(II)-cyclen-attached
agarose beads for enrichment of cysteine-containing molecules.
AB - Cysteine-containing biomolecules are attractive targets in the study of thiol
biology. Here we introduce a novel method for the selective enrichment of thiol
containing molecules using a thiol-capture zinc(II) complex of 1,4,7,10
tetraazacyclododecane (Zn(2+)-cyclen). Recognition of N-acetylcysteine amide by
Zn(2+)-cyclen has been studied by potentiometric pH titration, revealing
formation of a 1:1 thiolate-bound Zn(2+)-cyclen complex with a large thiolate
affinity constant of 10(6.2)M(-1) at 25 degrees C and I=0.10M (NaCl). The Zn(2+)
bound thiolate anion is unexpectedly stable in aqueous solution at pH 7.8 under
atmospheric conditions for a few days. These findings have contributed to the
development of a convenient method for separation of thiol compounds by using a
micropipette tip. A 200MUL micropipette tip containing 10MUL of hydrophilic cross
linked agarose beads attached to Zn(2+)-cyclen moieties was prepared. All steps
for thiol-affinity separation (binding, washing, and eluting) are conducted using
aqueous buffers at room temperature. The entire separation protocol requires less
than 15min per sample. We demonstrate practical example separations of cysteine
containing molecules. This micropipette tip method would be used preferentially
as an alternative to existing tools for reliable enrichment of thiol-containing
molecules.
PMID- 27498091
TI - Maternal Emotional Availability and Its Association with Maternal
Psychopathology, Attachment Style Insecurity and Theory of Mind.
AB - BACKGROUND/AIMS: High maternal emotional availability (EA) positively affects
various domains of child development. However, the question of which factors
promote or hinder maternal EA has not been investigated systematically. The
present study investigated several maternal characteristics, namely maternal
psychopathology, maternal attachment style insecurity, and theory of mind (ToM)
as possible factors that influence maternal EA. METHODS: The sample was comprised
of 56 mothers and their preschool-aged children. Half of the mothers were
diagnosed with postpartum depression and or anxiety disorders according to DSM
IV, and the other half were healthy controls. RESULTS: The results showed that
both low maternal attachment style insecurity and high ToM skills significantly
predicted maternal EA sensitivity, independently from maternal postpartum and
concurrent psychopathology and education. Moreover, maternal attachment style
insecurity fully mediated the link between maternal postpartum psychopathology
and sensitivity. CONCLUSION: The findings suggest that maternal attachment style
security can buffer negative effects of maternal psychopathology on maternal
sensitivity in the mother-child interaction.
PMID- 27498092
TI - Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in
Unstable Carotid Atherosclerotic Plaques.
AB - OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes
associated with carotid plaque instability and their protein products at a local
and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid
endarterectomy (CEA) were classified as stable or unstable using clinical,
histological, ultrasound, and transcranial Doppler criteria, and compared using
whole genome microarray chips. Initial results of differentially expressed genes
were validated by quantitative reverse transcriptase polymerase chain reaction in
an independent group of 96 patients undergoing CEA. The protein product of genes
significantly differentially expressed between patients with stable and unstable
plaques were analysed by plaque immunohistochemistry and serum protein
quantification by enzyme-linked immunosorbent assay on a further independent
cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was
significantly upregulated in plaques from patients with clinically unstable
disease (p < .001). Cathepsin G expression was upregulated in histologically
unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher
in patients with clinically unstable plaques (p = .02). Immunohistochemical
staining for CCL19 demonstrated positive staining in histologically and
clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell
lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS:
CCL19 is significantly overexpressed in patients with unstable carotid
atherosclerotic plaques and may be a possible novel biomarker for identifying
high-risk patients in whom more urgent intervention may be indicated.
PMID- 27498093
TI - [Simple strategy to promote well-being in cancer patients: Nurse-patient dialogue
during the administration of chemotherapy].
PMID- 27498095
TI - Rosiglitazone influences adipose tissue distribution without deleterious impact
on heart rate variability in coronary heart disease patients with type 2
diabetes.
AB - INTRODUCTION: Obesity is associated with decreased heart rate variability (HRV).
Rosiglitazone, a PPARgamma agonist, is generally associated with increases in
body mass. PURPOSE: To assess whether the gain in body mass and adiposity
expected from rosiglitazone treatment has an influence on HRV in patients with
type 2 diabetes and coronary artery disease. METHODS: One hundred and twenty-five
patients with type 2 diabetes and coronary artery disease aged between 40 and 75
years were studied. Anthropometric measurements: (1) body mass index (BMI), (2)
waist circumference (WC), (3) abdominal computed tomography (CT) scan, and HRV
(using a 24 h Holter) were measured at baseline and after 12 months of treatment.
Patients were randomized to rosiglitazone or placebo regimen. RESULTS: In the
rosiglitazone vs. placebo group, there were significant increases in body mass
[3.5 (2.6;4.4); mean (95 % CI) vs. 0.2 (-0.4;0.8)] kg), BMI [1.3 (1.0;1.6) vs.
0.1 (-0.1;0.3) kg/m2], WC [2.1 (0.9;3.3) vs. 0.4 (-0.4;1.2) cm, all p <= 0.001]
and subcutaneous adipose tissue [253 (187;319) vs. 6 (-24;36) cm3, p <= 0.001]
without statistically significant changes in visceral adipose tissue [-22 (
91;47) vs. 57 (43;71) cm3, p = 0.546], respectively. There was no change in HRV
in either group after 12 months. There were no correlations between changes in
HRV variables and fat distribution. CONCLUSION: Our results suggest that changes
in adiposity indices observed after 12 months of rosiglitazone therapy have no
deleterious influence on HRV in patients with type 2 diabetes and coronary artery
disease.
PMID- 27498097
TI - Further research needed for severe and chronic depression in specialist mental
health services.
PMID- 27498096
TI - Superficial siderosis associated with peripheral autonomic failure and
tetraventricular hydrocephalus: a case report.
AB - We describe the case of a man whose initial clinical presentation included
sensorineural hearing loss and orthostatic hypotension. The patient was diagnosed
with superficial siderosis associated with peripheral autonomic failure and
tetraventricular hydrocephalus.
PMID- 27498094
TI - Exchange of Sex for Drugs or Money in Adolescents and Young Adults: An
Examination of Sociodemographic Factors, HIV-Related Risk, and Community Context.
AB - The goal of this research was to examine associations among sociodemographic
factors, HIV risk, and community context (e.g., economic insecurity, job
training, housing instability, crime victimization, and perceived community
norms) in adolescents and young adults who ever exchanged sex for drugs or money.
Anonymous survey data were collected using ACASIs at community venues where
adolescents and young adults congregate in resource-challenged, STI prevalent,
urban, US neighborhoods. Conventional descriptive statistics, Fisher's exact
tests, and generalized estimating equations approaches were used to examine
associations. Participants (1818, 95.5 % of those screened eligible) were, on
average, aged 21.0 years; 42.2 % were males, and 4.6 % were transgender. Almost
one-third (32.1 %) identified as gay or lesbian, 18.1 % identified as bisexual;
66.2 % were Black and 21.0 % were Hispanic; 1.3 % was 'living on the street'. A
sizeable proportion reported HIV-related risk: 16.3 % exchanged sex, 12.6 % had
sex with someone they knew to be HIV-infected, 7.8 % had sex with someone who
injected drugs, and 1.3 % injected drugs. Multivariate comparisons identified a
number of variables (e.g., being male or transgender, homelessness, sex with a
partner who has HIV, STI history, unemployment, job training access, housing
instability, crime victimization, perceived community norms) that were
significantly associated with exchange of sex (p < 0.05). This research
contributes to the knowledge-base regarding exchange of sex among adolescents and
young adults, particularly as it relates to community context. Longitudinal
studies to describe the trajectory of social, health, and physical risks and
consequences are needed for development of effective evidence-based prevention
strategies.
PMID- 27498098
TI - Efficacy and cost-effectiveness of a specialist depression service versus usual
specialist mental health care to manage persistent depression: a randomised
controlled trial.
AB - BACKGROUND: Persistent moderate or severe unipolar depression is common and
expensive to treat. Clinical guidelines recommend combined pharmacotherapy and
psychotherapy. Such treatments can take up to 1 year to show an effect, but no
trials of suitable duration have been done. We investigated the efficacy and cost
effectiveness of outpatient-based, specialist depression services (SDS) versus
treatment as usual (TAU) on depression symptoms and function. METHODS: We did a
multicentre, single-blind, patient-level, parallel, randomised controlled trial
(RCT), as part of the National Institute for Health Research (NIHR) Collaboration
for Leadership in Applied Health Research and Care (CLAHRC) study, in three
mental health outpatient settings in England. Eligible participants were in
secondary care, were older than 18 years, had unipolar depression (with a current
major depressive episode, a 17-item Hamilton Depression Rating Scale [HDRS17]
score of >=16, and a Global Assessment of Function [GAF] score of <=60), and had
not responded to 6 months or more of treatment for depression. Randomisation was
stratified by site with allocation conveyed to a trial administrator, with
research assessors masked to outcome. Patients were randomised (1:1) using a
computer-generated pseudo-random code with random permuted blocks of varying
sizes of two, four, or six to either SDS (collaborative care approach between
psychiatrists and cognitive behavioural therapists for 12 months, followed by
graduated transfer of care up to 15 months) or to the TAU group. Intention-to
treat primary outcome measures were changes in HDRS17 and GAF scores between
baseline and 6, 12, and 18 months' follow-up. We will separately publish follow
up outcomes for months 24 and 36. Clinical efficacy and cost-effectiveness were
examined from health and social care persp ectives at 18 months, as recommended
by the National Institute for Health and Care Excellence. This trial is
registered at ClinicalTrials.gov (NCT01047124) and the ISRCTN registry
(ISRCTN10963342); the trial has ended. FINDINGS: 307 patients were assessed for
eligibility between Dec 21, 2009, and Oct 31, 2012. 94 patients were assigned to
TAU and 93 patients to SDS, and were included in intention-to-treat analyses. The
changes from baseline to 6 months in HDRS17 and GAF scores did not significantly
differ between treatment groups (mean change difference in HDRS17 score -1.01
[95% CI -3.30 to 1.28], p=0.385; and in GAF score 1.33 [-2.92 to 5.57], p=0.538).
Primary outcome data were available for 134 (72%) patients at 12 months. We noted
no differences at 12 months' follow-up between SDS and TAU for mean HDRS17 score
(14.8 [SD 7.9] in the SDS group vs 17.2 [7.3] in the TAU group, p=0.056) or GAF
score (60.4 [11.7] vs 55.8 [12.7], p=0.064), and the changes from baseline to 12
months in HDRS17 and GAF scores did not significantly differ between treatment
groups (mean change difference in HDRS17 score -2.45 [95% CI -5.04 to 0.14],
p=0.064; and in GAF score 4.12 [-0.11 to 8.35], p=0.056). The mean change in
HDRS17 score from baseline to 18 months was significantly improved in the SDS
group compared with the TAU group (13.6 [SD 8.8] in the SDS group vs 16.1 [6.6]
in the TAU group; mean change difference -2.96 [95% CI -5.33 to -0.59], p=0.015),
but the GAF scores showed no significant differences between the groups (61.2 [SD
13.0] vs 57.7 [11.9]; mean change difference 3.82 [-9.3 to 8.57], p=0.113). We
reported no deaths, but one (1%) patient was admitted to hospital for myocardial
infarction, and three episodes of self-harm were reported in three (2%) patients
(two receiving TAU, one receiving SDS care). The incremental cost-effectiveness
ratio of SDS versus TAU was L43 603 per quality-adjusted life-year.
INTERPRETATION: Compared with usual specialist mental health secondary care, SDS
might improve depression symptoms for patients with persistent moderate to severe
depression, but functional outcomes and economic benefits are equivocal. FUNDING:
National Institute for Health Research Collaboration for Leadership in Applied
Health Research and Care, UK Medical Research Council, Nottinghamshire Healthcare
NHS Foundation Trust, Derbyshire Healthcare NHS Foundation Trust, Cambridgeshire
and Peterborough NHS Foundation Trust, University of Nottingham.
PMID- 27498100
TI - Pharmacokinetics, Pharmacodynamics and Population Pharmacokinetic/Pharmacodynamic
Modelling of Bilastine, a Second-Generation Antihistamine, in Healthy Japanese
Subjects.
AB - BACKGROUND AND OBJECTIVES: Bilastine is a novel second-generation antihistamine
for the symptomatic treatment of allergic rhinitis and urticaria. The objective
of this study was to evaluate the pharmacokinetics, pharmacodynamics, and
tolerability of bilastine following single and multiple oral doses in healthy
Japanese subjects. The pharmacokinetic and pharmacodynamic profiles were compared
with those reported in Caucasian subjects. METHODS: In a single-blind,
randomized, placebo-controlled, parallel-group, single- and multiple-ascending
dose study, bilastine tablets were administered at single doses of 10, 20, and 50
mg (Part I), and once daily for 14 days at 20 and 50 mg (Part II). RESULTS: After
single oral doses, maximum plasma concentrations (C max) were reached at 1.0-1.5
h postdose. Plasma exposure [C max and area under the plasma concentration-time
curve (AUC)] increased dose-proportionally at single doses of 10-50 mg. In
repeated-dose administration, no remarkable differences were observed between Day
1 and Day 14 for C max or AUC. For inhibitory effects on wheal and flare
response, bilastine 20 and 50 mg showed significant inhibition from 1.5 h after
administration as compared with placebo, and the significant effect persisted for
24 h after administration. The rates of adverse events (AEs) were comparable
between bilastine and placebo in both Part I and Part II. In addition, no dose-
or administration period-dependent tendency of increase in rate of AEs or
worsening of severity was observed. CONCLUSION: Bilastine exhibits similar single
and multiple-dose pharmacokinetic and pharmacodynamic characteristics in healthy
Japanese subjects compared with those observed in Caucasian subjects in previous
studies.
PMID- 27498099
TI - How do different delivery schedules of tailored web-based physical activity
advice for breast cancer survivors influence intervention use and efficacy?
AB - PURPOSE: The purpose of the study is to investigate the impact of differing
delivery schedules of computer-tailored physical activity modules on engagement
and physical activity behaviour change in a web-based intervention targeting
breast cancer survivors. METHODS: Insufficiently active breast cancer survivors
(n = 492) were randomly assigned to receive one of the following intervention
schedules over 12 weeks: a three-module intervention delivered monthly, a three
module intervention delivered weekly or a single module intervention. Engagement
with the website (number of logins, time on site, modules viewed, action plans
completed) was measured using tracking software. Other outcomes (website
acceptability, physical activity behaviour) were assessed using online surveys.
Physical activity outcomes were analysed using regression models for both study
completers and when applying intention-to-treat (using multiple imputation).
RESULTS: Completers allocated to the monthly module group rated the intervention
higher (b = 2.2 95 % CI = 0.02-4.53) on acceptability and had higher levels of
resistance-training (IRR = 1.88, 95 % CI = 1.16-3.04) than those in the single
module group. When accounting for missing data, these differences were no longer
significant. The completion of at least two action plans was higher among those
allocated to the monthly module group compared to those in the weekly module
group (53 vs 40 %, p = 0.02); though the completion of at least two modules was
higher in the weekly module group compared to the monthly module group (60 vs 46
%; p = 0.01). There were no other significant between group differences observed.
CONCLUSION: This study provides preliminary evidence that web-based computer
tailored interventions can be used to increase physical activity among breast
cancer survivors. Further, there were some outcome differences based on how the
tailored modules were delivered, with the most favourable outcomes observed in
the monthly delivery group. IMPLICATIONS FOR CANCER SURVIVORS: This study will be
useful for informing the design of future web-based interventions targeting
breast cancer survivors.
PMID- 27498102
TI - Computed tomography value and tunnel enlargement of round and rounded rectangular
femoral bone tunnel for anterior cruciate ligament reconstruction.
AB - INTRODUCTION: We developed a novel technique for anatomical single-bundle
anterior cruciate ligament (ACL) reconstruction: creation of a rounded
rectangular femoral bone tunnel. The purpose of this study was to compare the
computed tomography (CT) value and tunnel enlargement ratio of the femoral bone
tunnel with those of round tunnel ACL reconstruction. MATERIALS AND METHODS: We
included 39 knees that underwent round tunnel ACL reconstruction and 42 that
underwent rounded rectangular ACL reconstruction. To evaluate the CT value, we
compared the CT images approximately 1 week after surgery. Making a parallel
slice toward the opening of bone tunnels to a depth of 3 mm, we evaluated the CT
value of eight directions in the bone tunnel wall. To evaluate tunnel
enlargement, we compared CT images approximately 1 week after surgery with images
taken 3 months after surgery. Using a parallel slice toward the opening of the
bone tunnel, we measured the bone tunnel area and calculated the tunnel
enlargement ratio. The level of significance was P < 0.05, and the t test was
used for statistical analyses. RESULTS: The CT value was significantly increased
for the rounded rectangular tunnel in comparison with the round tunnel in almost
all directions (P < 0.05). The rounded rectangular tunnel area enlargement ratio
was significantly lower (round, 110 +/- 38 %; rounded rectangular, 73 +/- 37 %; P
= 0.001). CONCLUSION: The rounded rectangular tunnel could have a compression
effect on the cancellous bone and reduce enlargement of the bone tunnel.
PMID- 27498101
TI - ICU Management of the Potential Organ Donor: State of the Art.
AB - End-organ failure is associated with high mortality and morbidity, in addition to
increased health care costs. Organ transplantation is the only definitive
treatment that can improve survival and quality of life in such patients;
however, due to the persistent mismatch between organ supply and demand, waiting
lists continue to grow across the world. Careful intensive care management of the
potential organ donor with goal-directed therapy has the potential to optimize
organ function and improve donation yield.
PMID- 27498103
TI - Biomechanical comparison between the modified rolling-hitch and the modified
finger-trap suture techniques.
AB - PURPOSE: The purpose of this study was to characterize the biomechanical effect
of two grasping suture techniques used during ligament reconstruction: the
modified rolling-hitch (MRH) and the modified finger-trap (MFT). METHODS: Flexor
profundus tendons were harvested from fresh pig hind-leg trotters. Each specimen
was mounted on an electro-mechanic universal testing machine (Instron 3367). In
half of all tendons (15 specimens), the suture was passed around the tendon
following the MRH knot (Group 1). In the remaining half of all tendons (15
specimens), the suture was passed over a distance of 30 mm according to the MFT
suture technique (Group 2). As per standard intra-operative technique, a 1 cm
residual tendon stub was left free from suture in all samples. All specimens were
preconditioned to a load of 50 N for 10 min, followed by three cycles loading
between 50 and 120 N. At this point, each sample was cyclically tensioned between
35 and 240 N, at 1 Hz for 200 cycles. Load-to-failure test was then carried out
at a rate of 200 mm/min. RESULTS: Rupture of the suture material at the knot was
the mode of failure in all specimens during the loaded to failure test.
Significant difference was found between Group 1 vs Group 2 for the elongation
between the 0th cycle and 10th cycle, the elongation between the 10th cycle and
200th cycle, the mean stiffness at the 10th cycle, and the mean stiffness at the
190th cycle. No significant differences were noted between Group 1 and Group 2
concerning the ultimate load-to-failure. CONCLUSION: This study showed that both
suture methods appear to be biomechanically effective in a porcine tendon model.
However, the single-knot grasping technique (MRH) provided superior biomechanical
properties compared with the MFT technique.
PMID- 27498104
TI - Decreased QOL and muscle strength are persistent 1 year after intramedullary
nailing of a tibial shaft fracture: a prospective 1-year follow-up cohort study.
AB - INTRODUCTION: To evaluate the development in patient-reported quality of life
(QOL) and muscle strength in the period from surgery to 12 months postoperatively
after intramedullary nailing of a tibial shaft fracture. MATERIALS AND METHODS:
The design was a prospective, follow-up cohort study. QOL was measured with the
questionnaire Eq5D-5L and compared to norm data from a reference population.
Recordings of pain and contralateral muscle strength (isometric maximal voluntary
contraction (MVC) for knee flexion and extension were collected at 6 weeks, 3, 6,
and 12 months postoperatively. Ipsilateral MVCs were recorded at 6 and 12 months.
RESULTS: Forty-nine patients were included. The mean age at the time of fracture
was 43.1 years (18-79 years). Twelve months postoperatively, the mean Eq5D-5L
index was 0.792 (95 % CI 0.747-0.837). Throughout the 12 months postoperatively,
patients reported worse QOL compared to the reference population. Six and 12
months after surgery patients demonstrated decreased muscle strength in the
injured leg compared to the non-injured leg for knee extension and flexion (P <
0.001). Twelve months postoperatively, increasing relative difference in muscle
strength during knee extension show a fair correlation to worse QOL (R = 0.541, P
< 0.001). CONCLUSIONS: Throughout the 12 months postoperatively, patients
reported worse QOL compared to the reference population. Muscle strength in the
non-injured leg improved over time and was higher after 6 and 12 months compared
with the injured leg.
PMID- 27498105
TI - Three-dimensional analysis of the shoulder motion in patients with massive
irreparable cuff tears after latissimus dorsi tendon transfer (LDT).
AB - INTRODUCTION: Latissimus dorsi tendon transfer (LDT) is a recent method for
surgical treatment of massive, irreparable posterosuperior cuff tears (MIPCT). So
far, there are no studies on the quantitative motion analysis of the shoulder and
latissimus dorsi (LD) muscle activation after LDT. The changes in shoulder
movements after LDT can be objectively assessed by the 3-D motion analysis. These
changes may not be due to an increased activity of the LD muscle as external
rotator. MATERIALS AND METHODS: The shoulder kinematics of nine patients with
MIPCT were recorded through a 3-D motion analysis system, before LTD (T0), and
after 3 (T1) and 6 (T2) months post-LDT. Maximal shoulder flexion-extension,
abduction-adduction, and horizontal abduction-adduction, and the internal and
external circumduction of the shoulder joint were measured during upright
standing posture. Surface EMG activity of the LD muscle was recorded during both
internal rotation (IR) and external rotation (ER) tasks in three different
postures. RESULTS: A significant increase of shoulder movements was observed at
T2 compared with T0 for almost all motor tasks. A significant effect of LDT was
also found on LD-IR/ER ratio in posture 1 at T2 compared with T0 and T1. No
significant effects were found for the LD-IR/ER ratio in the other postures.
CONCLUSIONS: Our study indicates that LDT is effective in shoulder motion
recovery. Such improvement is not associated with a change in function of the LD
muscle, which may be induced by a depression of the humeral head into the glenoid
cavity instead.
PMID- 27498106
TI - Return to prelesional Tegner level after anatomic anterior cruciate ligament
reconstruction.
AB - INTRODUCTION: Injury and surgery of the anterior cruciate ligament (ACL) are very
frequent within the sports environment. The purpose of the present study is to
assess the level at which a group of athletes were able to return to play (RTP)
after ACL reconstruction, and most importantly, the time for RTP. MATERIALS AND
METHODS: A prospective study with patients who presented an ACL injury and
underwent ligament reconstruction surgery; a bone-tendon-bone reconstruction and
a minimum follow-up of 24 months. The rates of RTP as well as correlations with
IKDC and KT-1000 were collected. RESULTS: 42 patients were included (mean age
31.7 years old). Mean Tegner level was 6.7. 9.5 % of patients returned to sports
6 months after surgery, 52.3 % at 1 year, and 73.8 % at 2 years after ACL
reconstruction. 11 patients did not achieve their preoperative Tegner level after
2 years of follow-up. Levels of KT-1000 of the operated side were normal, and
IKDC levels reached 90 % of total. CONCLUSIONS: Fear to a new injury,
psychological factors, personality, type of life, and sports level previous to
the injury are factors that influence when it comes to RTP after an ACL surgery.
Level of evidence Level II descriptive analysis.
PMID- 27498107
TI - A simple approach for the preoperative assessment of sacral morphology for
percutaneous SI screw fixation.
AB - BACKGROUND: Percutaneous sacroiliac screw fixation under fluoroscopic control is
an effective method for posterior pelvic ring stabilization. However, sacral
dysmorphism has a high risk of L5 nerve injury. This study describes a simple
method for the preoperative assessment of the sacral morphology using CT scans
with widely available tools. MATERIALS AND METHODS: CT scans of 1000 patients
were analyzed. True inlet, outlet, and lateral views of the sacrum were obtained
using a two-dimensional reconstruction tool to align the sacrum in a reproducible
manner. Corridor morphology in the inlet view was measured to calculate different
morphological types: (1) Ascending type, (2) Horizontal type, and (3) Descending
type. In a second step, the corridor was analyzed for the presence of an anterior
indentation of the sacrum between the SI joint and the midsagittal plane with
proximity to the nerve root L5, which, therefore, may be harmed during screw
misplacement. RESULTS: A notch was found in the majority of cases with relative
frequencies ranging from 69 % (upper quartile of S1) to 95 % (upper quartile of
S2). Descending types were, by far, the most frequent corridor type with one
exception: In the upper quartile of S1, the ascending type was the most frequent
corridor (71 %). Horizontal types were less frequent with a relative incidence
between 2 and 14 %. DISCUSSION: This study should increase the awareness for
sacral dysmorphism, emphasize the importance of a preoperative assessment of the
osseous corridor, and provide a simple method for the preoperative assessment
with widely available tools.
PMID- 27498108
TI - Preservation of bursal-sided tendon in partial-thickness articular-sided rotator
cuff tears: a novel arthroscopic transtendon anatomic repair technique.
AB - INTRODUCTION: The purpose of this study was to introduce a novel arthroscopic
transtendon anatomic repair technique that spares the intact bursal-sided tendon
in articular-sided partial-thickness rotator cuff tears (PTRCT) and to present
shoulder functional outcomes in patients with symptomatic articular-sided PCRCT
that involves more than 50 % of its thickness after arthroscopic repair using a
novel technique. MATERIALS AND METHODS: Eighteen patients with symptomatic
articular-sided PCRCT involving more than 50 % of the tendon's thickness
underwent arthroscopic repair using a devised technique. The devised technique
restores only the torn articular portion of the rotator cuff at the anatomical
footprint using a suture anchor, and preserves the integrity of the corresponding
bursal-sided tendon by tying knots at the most lateral bursal side on the
subacromial space. Clinical and functional outcome using ASES and Constant scores
were evaluated. The structural integrity of the rotator cuff was evaluated by MRI
at 6 months postoperatively. RESULTS: Pain relief and shoulder functional
outcomes were encouraging during the recovery phase after operation. ASES
(preoperative 54.0 +/- 10.3 to postoperative 92.6 +/- 8.0), Constant score (61.2
+/- 8.5-88.0 +/- 5.3), VAS for pain (4.9 +/- 2.6-0.6 +/- 0.7) improved
significantly after arthroscopic transtendon anatomic repair (p < 0.001). No
patients had rotator cuff retears on 6-month MRI. No complications related to
surgical procedures had occurred. CONCLUSION: The devised technique of
arthroscopic transtendon repair provided satisfactory functional outcomes without
postoperative discomforts. This technique minimizes over-tightening of the
articular layer and reduces tension mismatches between the articular and bursal
layers, which are considered as important factors for improvement of
postoperative shoulder motion.
PMID- 27498110
TI - Lupus nephritis biomarkers.
AB - Lupus nephritis (LN), a potentially destructive outcome of SLE, is a real
challenge in the management of SLE because of the difficulty in diagnosing its
subclinical onset and identifying relapses before serious complications set in.
Conventional clinical parameters such as proteinuria, GFR, urine sediments, anti
dsDNA and complement levels are not sensitive or specific enough for detecting
ongoing disease activity in lupus kidneys and early relapse of nephritis. There
has long been a need for biomarkers of disease activity in LN. Such markers
ideally should be capable of predicting early sub-clinical flares and could be
used to gauge response to therapy, thus obviating the need for serial renal
biopsies with their possible hazardous complications. Since urine can be readily
obtained, it lends itself as an obvious biological substrate. In this review, the
use of urine and serum as sources of lupus nephritis biomarkers is described, and
the results of biomarker discovery studies using candidate and proteomic
approaches are summarized.
PMID- 27498109
TI - Changes of regulatory T cells, transforming growth factor-beta and interleukin-10
in patients with type 1 diabetes mellitus: A systematic review and meta-analysis.
AB - Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and
transforming growth factor-beta (TGF-beta) have implicated in the development of
type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear.
Hereby we performed a systematic review and meta-analysis to characterize the
changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls
from 40 case-control studies were eventually included in the pooling analysis.
Compared with the controls, T1DM patients had decreased frequency of
CD4(+)CD25(+)Treg (p=0.0003), CD4(+)CD25(+)Foxp3(+)Treg (p=0.020), and the level
of TGF-beta (p=0.030). Decrease in IL-10 (p=0.14) was not significant. All the
changes remained significant when the studies with low NOS scores and publication
bias were excluded. In conclusion, peripheral Treg and serum TGF-beta are reduced
in type 1 diabetes mellitus whereas changes in serum IL-10 are not significant.
PMID- 27498111
TI - A dedicated vascular access clinic for children on haemodialysis: Two years'
experience.
AB - BACKGROUND: Arteriovenous fistula (AVF) formation for long-term haemodialysis in
children is a niche discipline with little data for guidance. We developed a
dedicated Vascular Access Clinic that is run jointly by a transplant surgeon,
paediatric nephrologist, dialysis nurse and a clinical vascular scientist
specialised in vascular sonography for the assessment and surveillance of AVFs.
We report the experience and 2-year outcomes of this clinic. METHODS: Twelve new
AVFs were formed and 11 existing AVFs were followed up for 2 years. All children
were assessed by clinical and ultrasound examination. RESULTS: During the study
period 12 brachiocephalic, nine basilic vein transpositions and two radiocephalic
AVFs were followed up. The median age (interquartile range) and weight of those
children undergoing new AVF creation were 9.4 (interquartile 3-17) years and 26.9
(14-67) kg, respectively. Pre-operative ultrasound vascular mapping showed
maximum median vein and artery diameters of 3.0 (2-5) and 2.7 (2.0-5.3) mm,
respectively. Maturation scans 6 weeks after AVF formation showed a median flow
of 1277 (432-2880) ml/min. Primary maturation rate was 83 % (10/12). Assisted
maturation was 100 %, with two patients requiring a single angioplasty. For the
11 children with an existing AVF the maximum median vein diameter was 14.0 (8.0
26.0) mm, and the median flow rate was 1781 (800-2971) ml/min at a median of 153
weeks after AVF formation. Twenty-two AVFs were used successfully for dialysis, a
median kt/V of 1.97 (1.8-2.9), and urea reduction ratio of 80.7 % (79.3-86 %) was
observed. One child was transplanted before the AVF was used. CONCLUSIONS: A
multidisciplinary vascular clinic incorporating ultrasound assessment is key to
maintaining young children on chronic haemodialysis via an AVF.
PMID- 27498113
TI - The anatomical limits and oncological benefit of lymphadenectomy in muscle
invasive bladder cancer.
AB - BACKGROUND: Lymphadenectomy is part of standard treatment for muscle invasive
bladder cancer. The objective of this review is to provide an up-to-date review
on the available scientific evidence in this field. ACQUISITION OF EVIDENCE: We
conducted a literature review in PubMed of relevant articles up to the present
(2016). We found a systematic review published in 2014 that included the
comparative studies published up to that year, and we updated the review with new
relevant publications since that date. SYNTHESIS OF THE EVIDENCE: The number of
lymph nodes is not the best indicator for determining the quality of the
lymphadenectomy given that the number can vary depending on numerous factors that
depend not only on the surgeon but also on the patient and on the pathologist.
The definition of standard anatomical territories and a meticulous extraction of
the lymph nodes in these territories are more reproducible than the numbers of
nodes removed. The optimal extension of lymphadenectomy is a topic of debate. The
evidence published to date indicates that any extension of lymphadenectomy is
better than not performing it, although it appears that limited lymphadenectomy
is insufficient for the oncological control of the disease and that superextended
lymphadenectomy provides no oncological benefit versus extended lymphadenectomy.
CONCLUSIONS: Despite a certain amount of controversy in terms of the optimal
extension of lymphadenectomy, performing lymphadenectomy in all cases appears to
be recommendable according to the available evidence. Extended lymphadenectomy
provides greater oncological benefit than more limited dissections, while more
extensive lymphadenectomies are not recommended.
PMID- 27498112
TI - A prospective cohort study of depression course, functional disability, and NEET
status in help-seeking young adults.
AB - PURPOSE: To examine the associations between depression course, functional
disability, and Not in Education or Training (NEET) status in a clinical sample
of young adults with mental health problems. METHODS: Young adults aged 15-25
years seeking help from four primary mental health services were invited to
participate in a prospective cohort study evaluating the course of psychiatric
disorders in youth. Demographic and clinical characteristics, including
depressive symptomatology and functioning, were evaluated through clinical
interview and self-report at baseline and 12 month follow-up. RESULTS: A total of
448 young adults participated (70 % female; M: 20.05 years, SD = 2.85). A
significant interaction effect for time and depression course was found, such
that those who became depressed reported an increase in functional disability and
those whose depression remitted reported a significant reduction in functional
disability. Developing depression was not a significant predictor of becoming
NEET and vice versa: remitted depression did not make a person more likely to
reengage in employment or education. CONCLUSIONS: This is the first study to
examine the course of depression, functional disability, and NEET rates among
help-seeking young adults. This study confirms the importance of symptom
reduction for improved functioning; however, functional disability remained
greater than that seen in young people in the community and there was no
association between a change in depression and a change in NEET status. These
results argue that services need to address functional outcomes and reengagement
with education and employment in addition to symptom reduction.
PMID- 27498114
TI - Sublethal Concentration of Beta-Cypermethrin Influences Fecundity and Mating
Behavior of Carposina sasakii (Lepidoptera: Carposinidae) Adults.
AB - The purpose of this study was to evaluate the sublethal effects of the beta
cypermethrin on calling behavior and fecundity of a major fruit-boring pest of
apple, Carposina sasakii Matsumura. The mating rate, fertility (total number of
eggs laid per female), and adult longevity of adults were remarkably decreased as
compared with that in control when the adults were exposed to 10% lethal
concentrations (LC10) of beta-cypermethrin (LC10? * LC10?), and the age-specific
survival rate (lx) was also negatively affected by sublethal beta-cypermethrin
especially for the LC10?* LC10? mating combination. However, the age-specific
fecundity (mx) was stimulated particularly in the combination of CK?* LC10?.
Furthermore, the oviposition period was prolonged and the number of eggs was
significantly increased for combinations of CK?* LC10? and LC10?* CK?. In the
mating experiments, males in control or LC10-beta-cypermethrin treatments
preferred to mate with females in control. It might be because of lower calling
rate of female survivors treated with sublethal beta-cypermethrin. Our data
indicate that treatment of beta-cypermethrin had a sublethal effect on the
development and production of C. sasakii, and their mating behavior changes in
surviving adults that may contribute to assortative mating.
PMID- 27498115
TI - Effects of Field History on Corn Root Injury and Adult Abundance of Northern and
Western Corn Rootworm (Coleoptera: Chrysomelidae).
AB - Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera:
Chrysomelidae), and northern corn rootworm, Diabrotica barberi Smith & Lawrence,
are major pests of corn (Zea mays L.). Corn producing Bacillus thuringiensis (Bt)
toxins are widely used to manage Diabrotica spp.; however, Bt resistance by D. v.
virgifera has led to high levels of feeding injury in the field. We tested
whether field history affected root injury and abundance of adult Diabrotica spp.
In 2013 and 2014, four types of cornfields were sampled: 1) recently rotated
fields, 2) continuous cornfields, 3) fields with a history of injury to Bt corn
(past problem fields), and 4) fields with greater than one node of injury to Bt
corn at the time of sampling (current problem fields). Data were collected on
field history, root injury, and the abundance of adult Diabrotica spp. from each
field. Root injury and the abundance of D. v. virgifera were significantly
greater in current problem fields compared to the other field types, while D.
barberi were significantly more abundant in recently rotated fields. Root injury
and the abundance of D. v. virgifera did not differ among recently rotated
fields, continuous cornfields, and past problem fields. Analysis of field history
showed that recently rotated fields were characterized by significantly less Bt
corn, soil-applied insecticides, and years planted to corn continuously. These
results suggest that greater cropping practice diversity can reduce management
inputs for Diabrotica spp.; however, its effects on resistance evolution remain
undetermined.
PMID- 27498116
TI - The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively
damaged proteins by the proteasome.
AB - One hallmark of aging is the accumulation of protein aggregates, promoted by the
unfolding of oxidized proteins. Unraveling the mechanism by which oxidized
proteins are degraded may provide a basis to delay the early onset of features,
such as protein aggregate formation, that contribute to the aging phenotype. In
order to prevent aggregation of oxidized proteins, cells recur to the 20S
proteasome, an efficient turnover proteolysis complex. It has previously been
shown that upon oxidative stress the 26S proteasome, another form, dissociates
into the 20S form. A critical player implicated in its dissociation is the Heat
Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and,
therefore, an increased capability to degrade oxidized proteins. The aim of this
study was to test whether or not Hsp70 is involved in cooperating with the 20S
proteasome for a selective degradation of oxidatively damaged proteins. Our
results demonstrate that Hsp70 expression is induced in HT22 cells as a result of
mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of
oxidized proteins and directly promotes their degradation by the 20S proteasome.
In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not
changed in recovery after oxidative stress and Hsc70 has no influence on the
removal of oxidatively damaged proteins. We were able to demonstrate in HT22
cells, in brain homogenates from 129/SV mice and in vitro, that there is an
increased interaction of Hsp70 with oxidized proteins, but also with the 20S
proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized
proteins with the 20S proteasome. Thus, our data clearly implicate an involvement
of Hsp70 oxidatively damaged protein degradation by the 20S proteasome.
PMID- 27498118
TI - Differentiating the Causes of Spontaneous Rib Fracture After Breast Cancer.
AB - Spontaneous rib fracture after treatment for primary breast cancer is not
uncommon. Although metastatic disease accounts for about 30% of spontaneous rib
fractures and should constitute the first line of diagnostic investigation, other
possible contributors include primary osteoporosis or secondary osteoporosis
resulting from cancer treatments. Chemotherapy-induced menopause, aromatase
inhibitors, radiation therapy, and long-term bisphosphonate use can all
contribute to bone fragility, including spontaneous rib fractures in the latter
3. Drawing on recent breast cancer practice guidelines as well as population
based studies of fracture risk for women with a history of breast cancer and
systematic reviews, this Perspective will provide an update on recent
developments in understanding how to differentiate the possible reasons for non
traumatic rib fracture in women treated for breast cancer. In addition to
describing the various possible causes of spontaneous rib fracture, the
recommended medical and imaging procedures for differentiating among the
potential causes will be presented.
PMID- 27498117
TI - Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS
production and ameliorates pulmonary arterial hypertension.
AB - Excessive levels of reactive oxygen species (ROS) and increased expression of
NADPH oxidases (Nox) have been proposed to contribute to pulmonary artery
hypertension (PAH) and other cardiovascular diseases (CVD). Nox enzymes are major
sources of ROS but the mechanisms regulating changes in Nox expression in disease
states remain poorly understood. Epigenetics encompasses a number of mechanisms
that cells employ to regulate the ability to read and transcribe DNA. Histone
acetylation is a prominent example of an epigenetic mechanism regulating the
expression of numerous genes by altering chromatin accessibility. The goal of
this study was to determine whether inhibition of histone deacetylases (HDAC)
affects the expression of Nox isoforms and reduces pulmonary hypertension. In
immune cells, we found that multiple HDAC inhibitors robustly decreased Nox2 mRNA
and protein expression in a dose-dependent manner concomitant with reduced
superoxide production. This effect was not restricted to Nox2 as expression of
Nox1, Nox4 and Nox5 was also reduced by HDAC inhibition. Surprisingly, Nox
promoter-luciferase activity was unchanged in the presence of HDAC inhibitors. In
macrophages and lung fibroblasts, ChIP experiments revealed that HDAC inhibitors
block the binding of RNA polymerase II and the histone acetyltransferase p300 to
the Nox2, Nox4 and Nox5 promoter regions and decrease histones activation marks
(H3K4me3 and H3K9ac) at these promoter sites. We further show that the ability of
CRISPR-ON to drive transcription of Nox1, Nox2, Nox4 and Nox5 genes is blocked by
HDAC inhibitors. In a monocrotaline (MCT) rat model of PAH, multiple HDAC
isoforms are upregulated in isolated pulmonary arteries, and HDAC inhibitors
attenuate Nox expression in isolated pulmonary arteries and reduce indices of
PAH. In conclusion, HDAC inhibitors potently suppress Nox gene expression both in
vitro and in vivo via epigenetically regulating chromatin accessibility.
PMID- 27498119
TI - Factors Associated With Disease Recurrence in Breast Cancer Patients With
Negative Sentinel Lymph Node Biopsy.
AB - INTRODUCTION: The objective of our study was to assess recurrence after negative
sentinel lymph node biopsy (SLNB) and to determine the risk factors related to
local and distant recurrence in this group of patients. MATERIALS AND METHODS: We
conducted a prospective observational study from 2006 to 2011. It included 607
patients with early-stage breast cancer and negative SLNB with a 5-year follow-up
period. RESULTS: The disease-free survival rate was 98.5% and 96.5% at 2 and 5
years, respectively. Multivariate analysis identified the following prognostic
factors for disease recurrence: tumor necrosis (hazard ratio [HR], 4.89; 95%
confidence interval [CI], 1.61-14.89; P = .005), lymphovascular invasion (HR,
3.46; 95% CI, 1.14-10.55; P = .029), T2 tumor size (HR, 4.35; 95% CI, 1.40-13.52;
P = .011), and moderate to severe lymphoplasmacytic stromal infiltration (HR,
3.06; 95% CI, 1.18-7.96; P = .022). CONCLUSION: Recurrence in patients with
negative SLNB was satisfactorily low. Nevertheless, determining the prognostic
factors related to a greater recurrence rate could help identify high-risk
patients and influence systemic adjuvant therapy.
PMID- 27498120
TI - Rapamycin reverses age-related increases in mitochondrial ROS production at
complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA,
and lipofuscin level, and increases autophagy, in the liver of middle-aged mice.
AB - Rapamycin consistently increases longevity in mice although the mechanism of
action of this drug is unknown. In the present investigation we studied the
effect of rapamycin on mitochondrial oxidative stress at the same dose that is
known to increase longevity in mice (14mgofrapamycin/kg of diet). Middle aged
mice (16months old) showed significant age-related increases in mitochondrial ROS
production at complex I, accumulation of mtDNA fragments inside nuclear DNA,
mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young
animals (4months old) in the liver. After 7weeks of dietary treatment all those
increases were totally or partially (lipofuscin) abolished by rapamycin, middle
aged rapamycin-treated animals showing similar levels in those parameters to
young animals. The decrease in mitochondrial ROS production was due to
qualitative instead of quantitative changes in complex I. The decrease in
mitochondrial protein lipoxidation was not due to decreases in the amount of
highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of
RAPTOR (of mTOR complex) and increased the amounts of the PGC1-alpha and ATG13
proteins. The results are consistent with the possibility that rapamycin
increases longevity in mice at least in part by lowering mitochondrial ROS
production and increasing autophagy, decreasing the derived final forms of damage
accumulated with age which are responsible for increased longevity. The decrease
in lipofuscin accumulation induced by rapamycin adds to previous information
suggesting that the increase in longevity induced by this drug can be due to a
decrease in the rate of aging.
PMID- 27498121
TI - Protective Role of Liriodendrin in Sepsis-Induced Acute Lung Injury.
AB - In current study, we investigated the role of liriodendrin, a constituent
isolated from Sargentodoxa cuneata (Oliv.) Rehd. Et Wils (Sargentodoxaceae), in
cecal ligation and puncture (CLP)-induced acute lung inflammatory response and
injury (ALI). The inflammatory mediator levels in bronchoalveolar lavage fluid
(BALF) were determined by enzyme-linked immunosorbent assay (ELISA). Pathologic
changes in lung tissues were evaluated via pathological section with hematoxylin
and eosin (H&E) staining. To investigate the mechanism whereby liriodendrin
regulates lung inflammation, the phosphorylation of the NF-kB (p65) and
expression of vascular endothelial growth factor (VEGF) were determined by
western blot assay. We show that liriodendrin treatment significantly improved
the survival rate of mice with CLP-induced sepsis. Pulmonary histopathologic
changes, alveolar hemorrhage, and neutrophil infiltration were markedly decreased
by liriodendrin. In addition, liriodendrin decreased the production of the
proinflammatory mediators including (TNF-alpha, IL-1beta, MCP-1, and IL-6) in
lung tissues. Vascular permeability and lung myeloperoxidase (MPO) accumulation
in the liriodendrin-treated mice were substantially reduced. Moreover,
liriodendrin treatment significantly suppressed the expression of VEGF and
activation of NF-kB in the lung. We further show that liriodendrin significantly
reduced the production of proinflammatory mediators and downregulated NF-kB
signaling in LPS-stimulated RAW 264.7 macrophage cells. Moreover, liriodendrin
prevented the generation of reactive oxygen species (ROS) by upregulating the
expression of SIRT1 in RAW 264.7 cells. These findings provide a novel
theoretical basis for the possible application of liriodendrin in clinic.
PMID- 27498122
TI - Echocardiography does not predict mortality in hemodynamically stable elderly
patients with acute pulmonary embolism.
AB - BACKGROUND: The evidence on the prognostic value of transthoracic
echocardiography (TTE) in elderly, hemodynamically stable patients with Pulmonary
Embolism (PE) is limited. OBJECTIVES: To evaluate the prevalence of common
echocardiographic signs of right ventricular (RV) dysfunction and their
prognostic impact in hemodynamically stable patients aged >=65years with acute PE
in a prospective multicenter cohort. METHODS: TTE was performed by cardiologists.
We defined RV dysfunction as a RV/left ventricular ratio >0.9 or RV hypokinesis
(primary definition) or the presence of >=1 or >=2 of 6 predefined
echocardiographic signs (secondary definitions). Outcomes were overall mortality
and mortality/non-fatal recurrent venous thromboembolism (VTE) at 30days,
adjusting for the Pulmonary Embolism Severity Index risk score and highly
sensitive troponin T values. RESULTS: Of 400 patients, 36% had RV dysfunction
based on our primary definition, and 81% (>=1 sign) and 53% (>=2 signs) based on
our secondary definitions, respectively. Using our primary definition, there was
no association between RV dysfunction and mortality (adjusted HR 0.90, 95% CI
0.31-2.58) and mortality/non-fatal VTE (adjusted HR 1.09, 95% CI 0.40-2.98).
Similarly, there was no statistically significant association between the
presence of >=1 or >=2 echocardiographic signs (secondary definitions) and
clinical outcomes. CONCLUSION: The prevalence of echocardiographic RV dysfunction
varied widely depending upon the definition used. There was no association
between RV dysfunction and clinical outcomes. Thus, TTE may not be suitable as a
stand-alone risk assessment tool in elderly patients with acute PE. CLINICAL
TRIAL REGISTRATION: http://clinicaltrials.gov. Identifier: NCT00973596.
PMID- 27498123
TI - Pharmacological properties of microneurotrophin drugs developed for treatment of
amyotrophic lateral sclerosis.
AB - Microneurotrophins (MNT's) are small molecule derivatives of
dehydroepiandrosterone (DHEA) and do not have significant interactions with sex
steroid receptors. MNT's retain high-affinity binding to protein tyrosine kinase
(Trk) receptors and can mimic many pleiotropic actions of neurotrophin (NT)
proteins on neurons. MNT's offer therapeutic potential for diseases such as
amyotrophic lateral sclerosis (ALS) where motor neurons (MN) degenerate. MNT's
cross artificial membranes mimicking the blood-brain barrier, are not major
substrates for ABC (ATP-binding cassette) transporters and are metabolized
rapidly by mouse but more slowly by human hepatocytes. A lead MNT (BNN27) and its
mono-oxidation metabolites enter mouse brain rapidly. RNA-sequencing measured
gene expression profiles of human H9eSC-(embryonic stem cell)-derived or CTL
(control) subject iPSC-(induced pluripotential stem cell)-derived MN's exposed to
NT proteins or MNT molecules. Expression ratios (relative to DMSO
(dimethylsulfoxide) vehicle) were calculated, and the resulting top 500 gene
lists were analyzed for Gene Ontology (GO) grouping using DAVID (Database for
Annotation, Visualization and Integrated Discovery). The MNT's BNN20, BNN23, and
BNN27 showed overlap of GO terms with NGF (nerve growth factor) and BDNF (brain
derived neurotrophic factor) in the H9eSC-derived MN's. In the iPSC-derived MN's
two (BNN20, BNN27) showed overlap of GO terms with NGF or BDNF. Each NT protein
had GO terms that did not overlap with any MNT in the MN cell lines.
PMID- 27498124
TI - A Pharmacokinetic and Pharmacodynamic Study of Maraviroc as Acute Graft-versus
Host Disease Prophylaxis in Pediatric Allogeneic Stem Cell Transplant Recipients
with Nonmalignant Diagnoses.
AB - Maraviroc is an allosteric small molecule antagonist of chemokine receptor type 5
(CCR5) and has been used in adult allogeneic hematopoietic stem cell transplant
(HSCT) recipients to prevent acute graft-versus-host disease (GVHD) of the
gastrointestinal (GI) tract and liver. The goal of this study was to establish
feasibility and pharmacokinetic and pharmacodynamic profiles of maraviroc in
pediatric HSCT recipients. Children ages 2 to 12 years were enrolled and
maraviroc was added to standard GVHD prophylaxis, which included a calcineurin
inhibitor and either steroids or mycophenolate mofetil. Maraviroc was started on
day -3 and administered at a dose of approximately 300 mg/m(2) orally twice daily
until day +30 after stem cell infusion. On days 0 and day +10, samples for
pharmacokinetic analysis were collected before the dose and 1, 2, 4, 6, 8, and 12
hours after maraviroc administration. Additional trough concentrations were
collected on days +7, 14, and 21. Patients were followed until day +100 for acute
GVHD. Functional blockade of CCR5 was assessed in a pharmacodynamic assay by flow
cytometry. Thirteen patients, median age of 4 years (range, 2 to 11 years), were
prospectively enrolled. Underlying diagnoses included a primary immune deficiency
(n = 6), hemoglobinopathy (n = 4), metabolic disorder (n = 1), and bone marrow
failure syndrome (n = 2). Patients received either a myeloablative preparative
regimen (n = 7) or a reduced-intensity conditioning regimen (n = 6). Cyclosporine
and methylprednisolone (n = 7) was the predominant GVHD prophylactic regimen,
followed by tacrolimus and mycophenolate mofetil (n = 4) and tacrolimus and
steroids (n = 2). Two formulations of maraviroc (150-mg tablets and 20-mg/mL
solution) were used on study. Mean (+/- SD) area under the concentration-time
curve from 0 to 12 hours was 4805 +/- 3265 hour * ng/mL on day 0 and 5917 +/-
4048 hour * ng/mL on day +10. Four patients developed grade 1 or 2 acute skin
GVHD before day +100 and were successfully treated. Two patients developed grade
3 acute GI GVHD on days +23 and +24 after HSCT and both had discontinued
maraviroc before development of GI GVHD. No adverse effects attributable to
maraviroc were observed and administration by enteral tubes was well tolerated by
children and accepted by parents. All evaluable patients demonstrated functional
CCR5 blockade on day 0. Administration of maraviroc is feasible in most pediatric
HSCT recipients with good safety and tolerability profile.
PMID- 27498125
TI - Characterization of a novel cell wall binding domain-containing Staphylococcus
aureus endolysin LysSA97.
AB - Endolysin from Staphylococcus aureus phage SA97 (LysSA97) was cloned and
investigated. LysSA97 specifically lyse the staphylococcal strains and
effectively disrupted staphylococcal biofilms. Bioinformatic analysis of LysSA97
revealed a novel putative cell wall binding domain (CBD) as well as two
enzymatically active domains (EADs) containing cysteine, histidine-dependent
amidohydrolases/peptidases (CHAP, PF05257) and N-acetylmuramoyl-L-alanine amidase
(Amidase-3, PF01520) domains. Comparison of 98 endolysin genes of S. aureus
phages deposited in GenBank showed that they can be classified into six groups
based on their domain composition. Interestingly, approximately 80.61 % of the
staphylococcal endolysins have a src-homology 3 (SH3, PF08460) domain as CBD, but
the remaining 19.39 %, including LysSA97, has a putative C-terminal CBD with no
homology to the known CBD. The fusion protein containing green fluorescent
protein and the putative CBD of LysSA97 showed a specific binding spectrum
against staphylococcal cells comparable to SH3 domain (PF08460), suggesting that
the C-terminal domain of LysSA97 is a novel CBD of staphylococcal endolysins.
PMID- 27498126
TI - High prevalence of DUOX2 gene mutations among children with congenital
hypothyroidism in central China.
AB - Congenial hypothyroidism (CH) is the most common congenital endocrine disease and
is treatable when recognized early enough. We investigated the genetic variants
in 12 children diagnosed with CH by newborn screening in Huangshi area central
China. Twelve genes commonly involved in CH development were studied. Genomic DNA
from peripheral blood was used to amplify all exons of the selected genes, and
the constructed sequencing libraries were subjected to next generation high
throughput DNA sequencing (NGS). Analysis of the sequencing results identified
rare genetic variants in 11 of the 12 patients (91.7%), and two novel rare
variants were found in DUOX2 gene and two in TPO gene. Mutations in DUOX2 gene
were identified in 10 patients (83.3%), and all these patients were found to
carry bi-allelic, tri-allelic mutations or compound mutations with other genes.
Recurrent DUOX2 mutations include K530X, R683L, R1110Q, and L1343F. Truncating,
splicing, and proven deleterious DUOX2 missense mutations were detected in 50% of
the patients. Mutations in TG gene were identified in four patients, and
mutations in TPO, THSR, SLC26A4 genes were identified, one in each patient,
respectively. The high prevalence of DUOX2 mutations in this cohort of children
with CH appears striking and surprising. The clinical implications were
discussed.
PMID- 27498127
TI - Societal cost of subcutaneous and intravenous trastuzumab for HER2-positive
breast cancer - An observational study prospectively recording resource
utilization in a Swedish healthcare setting.
AB - INTRODUCTION: Trastuzumab is part of the standard treatment for HER2-positive
breast cancer. The aim of this study was to estimate the societal value of
trastuzumab administered through subcutaneous (SC) injection compared to
intravenous (IV) infusion. METHODS: Female patients with HER2-positive breast
cancer receiving SC or IV trastuzumab were consecutively enrolled from five
Swedish oncology clinics from 2013 to 2015. Data on time and resource utilization
was collected prospectively using patient and nurse questionnaires. Societal
costs were calculated by multiplying the resource use by its corresponding unit
price, including direct medical costs (pharmaceuticals, materials, nurse time,
etc.), direct non-medical costs (transportation) and indirect costs (production
loss, lost leisure time). Costs were reported separately for patients receiving
trastuzumab for the first time and non-first time ("subsequent treatment").
RESULTS: In total, 101 IV and 94 SC patients were included in the study. The
societal costs were lower with SC administration. For subsequent treatments the
cost difference was ?117 (IV ?2099; SC ?1983), partly explained by a higher time
consumption both for nurses (14 min) and patients (23 min) with IV
administration. Four IV and 16 SC patients received trastuzumab for the first
time and were analysed separately, resulting in a difference in societal costs of
?897 per treatment. A majority of patients preferred SC to IV administration.
CONCLUSION: SC administration resulted in both less direct medical costs and
indirect costs, and was consequently less costly than IV administration from a
societal perspective in a Swedish setting.
PMID- 27498128
TI - IHC4 score plus clinical treatment score predicts locoregional recurrence in
early breast cancer.
AB - PURPOSE: Immunohistochemical 4 (IHC4) score plus Clinical Treatment Score (CTS)
is an inexpensive tool predicting risk of distant recurrence in women with early
breast cancer (EBC). IHC4 score is based on ER, PR, HER2 and Ki67 index. This
study explores the role of the combined score (IHC4 + CTS) in predicting risk of
locoregional recurrence (LRR) in women with EBC who had breast conservation
surgery (BCS) without adjuvant radiotherapy (study group). The secondary
objective was to evaluate the clinicopathological differences between our study
group and women who had adjuvant radiation following BCS (control group). METHODS
AND MATERIALS: Patients were selected from the local database over a 13-year
period. IHC testing was done where results were missing. Combined scores were
calculated using the appropriate formulae. RESULTS: Patients in the study group
(81 patients) had favorable clinicopathological features compared to the control
group (1406 patients). The Cox regression indicated a statistically significant
association between the combined score and the risk of LRR (p = 0.03). The
incidence of LRR was zero, 20% and 33.3% in the low, intermediate and high risk
groups respectively (p = 0.007). Margin status was the only variable not included
in the combined score. The Cox regression analysis demonstrated that the combined
score (p = 0.02) and the ordinal measure of margins (p = 0.03) were significant
independent predictors of LRR. CONCLUSION: This is the first study of its kind.
The IHC4 score + CTS can be used to identify low risk women who can potentially
avoid adjuvant radiotherapy.
PMID- 27498130
TI - Rheological Flow Behavior of Structural Polysaccharides from Edible Tender
Cladodes of Wild, Semidomesticated and Cultivated 'Nopal' (Opuntia) of Mexican
Highlands.
AB - The aim of this study was to quantify the content of polysaccharides of edible
tender cladodes (nopalitos) of three species of Opuntia and to evaluate the
rheological flow behavior of isolated polysaccharides. A completely randomized
experimental design was used to characterize a wild (O. streptacantha), a
semidomesticated (O. megacantha) and a domesticated (O. ficus-indica) species.
Mucilage content was higher (4.93 to 12.43 g 100 g-1 dry matter), tightly bound
hemicelluloses were lower (3.32 to 1.81 g 100 g-1 dry matter) and pectins and
loosely bound hemicelluloses were not different in wild than in domesticated
species. Aqueous solution/suspensions of mucilage, pectins, hemicellulose and
cellulose of all species showed non-Newtonian behavior under simple shear flow.
The flow behavior of the structural polysaccharides was well described by the
Ostwald de-Waele model. Pectins and mucilages exhibited the highest consistency
indexes (K values ranged from 0.075 to 0.177 Pasn) with a moderated shear
thinning behavior (n values ranged from 0.53 to 0.67). Cellulose dispersions
exhibited the most shear-thinning behavior (n values ranged from 0.17 to 0.41)
and hemicelluloses showed a tendency to Newtonian flow (n values ranged from 0.82
to 0.97). The rheological flow properties of these polysaccharides may be useful
to improve the textural and sensory qualities of some foods and pharmaceutical
materials. Moreover, they can emerge as functional ingredients mainly due to the
nutraceutical properties that have been attributed to nopalitos.
PMID- 27498129
TI - Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non
anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive
breast cancer: The TRAIN-2 study.
AB - BACKGROUND: The addition of pertuzumab to neoadjuvant trastuzumab-based
chemotherapy improves pathologic complete response rates in HER2-positive breast
cancer. However, increased toxicity has been reported with the addition of
pertuzumab, and this may differ between various chemotherapy backbone regimens.
We evaluated toxicities of pertuzumab when added to either FEC-T (5-fluorouracil,
epirubicin, cyclophosphamide, trastuzumab) or weekly paclitaxel, trastuzumab,
carboplatin (PTC). METHODS: The TRAIN-2 study is a neoadjuvant randomized
controlled trial in stage II and III HER2-positive breast cancer (NCT01996267).
Patients are randomly assigned to receive either three cycles of FEC-T plus
pertuzumab or three cycles of PTC plus pertuzumab, followed by six cycles of PTC
plus pertuzumab in both arms. Toxicities are described per treatment arm
according to the Common Toxicity Criteria for Adverse Events version 4.03.
RESULTS: This analysis includes 110 patients balanced over both treatment arms.
Neutropenia was the most common hematologic toxicity, with grade 3-4 occurring in
53% in the FEC-T-arm and in 51% in the PTC-arm. Febrile neutropenia occurred in
9% in the FEC-T arm and did not occur in the PTC-arm. Secondary G-CSF prophylaxis
was used in 35-40% of patients. Asymptomatic ejection fraction decrease grade 2
was observed in 24% in the FEC-T-arm and 11% in the PTC-arm. The most common
grade 3-4 non-hematologic toxicity was diarrhea (5% in the FEC-T-arm and 18% in
the PTC-arm). CONCLUSIONS: Pertuzumab in combination with FEC-T mostly causes
neutropenia, and when added to PTC mostly causes diarrhea. Significant cardiac
toxicity is rare with both regimens, and toxicity is overall well manageable.
PMID- 27498131
TI - Editorial overview: Biotic interactions: Communicative interactions of plants:
plant biology in the age of information.
PMID- 27498132
TI - Computed tomography imaging to quantify the area of the endocardial subvalvular
apparatus in hypertrophic cardiomyopathy - Relationship to outflow tract
obstruction and symptoms.
AB - BACKGROUND: Abnormalities of the endocardial subvalvular apparatus (SVA), which
includes the papillary muscles directly attached to the mitral leaflet and left
ventricular apical-basal muscle bundles, are occasionally identified in
hypertrophic cardiomyopathy (HCM). Their associations with left ventricular
outflow tract (LVOT) obstruction are unknown. METHODS: We retrospectively
reviewed cardiac computed tomography image data sets of 107 consecutive patients
with HCM [56 obstructive (HOCM) and 51 non-obstructive (HNOCM)] as well as 53
controls. We evaluated anomalies of the SVA, measured the cross-sectional area of
the SVA at the level of the LVOT, and subsequently assessed its correlation with
the LVOT pressure gradient with and without medication. RESULTS: The area of the
SVA was greater in HOCM than in HNOCM patients and in the control group (2.5 +/-
1.3 cm(2), 1.4 +/- 0.8 cm(2), and 0.9 +/- 0.6 cm(2), respectively; p < 0.0001).
Anomalies in the SVA were more often observed in the HOCM group than in the HNOCM
patients and controls (abnormal papillary muscles, 14%, 8%, and 0%, respectively;
P = 0.010; LV apical-basal muscle bundles, 73%, 65%, and 45%, respectively; P =
0.0094). Among HOCM patients, logistic regression analysis demonstrated that an
SVA area of 2.2 cm(2) was an independent risk factor of residual severe LVOT
obstruction (>=50 mmHg) after medication (odds ratio, 10.1; 95% confidence
interval, 2.05-49.80). CONCLUSION: An increased area of the endocardial
subvalvular apparatus could be an independent risk factor for clinically relevant
LVOT obstruction refractory to medication.
PMID- 27498133
TI - Reply to "Establishing the independence and clinical importance of non-alcoholic
fatty liver disease as a risk factor for cardiovascular disease".
PMID- 27498134
TI - Establishing the independence and clinical importance of non-alcoholic fatty
liver disease as a risk factor for cardiovascular disease.
PMID- 27498135
TI - Tracking cognitive processing stages with MEG: A spatio-temporal model of
associative recognition in the brain.
AB - In this study, we investigated the cognitive processing stages underlying
associative recognition using MEG. Over the last four decades, a model of
associative recognition has been developed in the ACT-R cognitive architecture.
This model was first exclusively based on behavior, but was later evaluated and
improved based on fMRI and EEG data. Unfortunately, the limited spatial
resolution of EEG and the limited temporal resolution of fMRI have made it
difficult to fully understand the spatiotemporal dynamics of associative
recognition. We therefore conducted an associative recognition experiment with
MEG, which combines excellent temporal resolution with reasonable spatial
resolution. To analyze the data, we applied non-parametric cluster analyses and a
multivariate classifier. This resulted in a detailed spatio-temporal model of
associative recognition. After the visual encoding of the stimuli in occipital
regions, three separable memory processes took place: a familiarity process
(temporal cortex), a recollection process (temporal cortex and supramarginal
gyrus), and a representational process (dorsolateral prefrontal cortex). A late
decision process (superior parietal cortex) then acted upon the recollected
information represented in the prefrontal cortex, culminating in a late response
process (motor cortex). We conclude that existing theories of associative
recognition, including the ACT-R model, should be adapted to include these
processes.
PMID- 27498136
TI - Effects of bisphenol A on male and couple reproductive health: a review.
AB - Bisphenol A (BPA) is a ubiquitous environmental toxicant with endocrine
disrupting properties and is suspected to affect human reproduction. The
objective of this review was to summarize the potential effects of male exposure
to BPA on markers of testicular function and couple reproductive outcomes. Five
epidemiologic studies on BPA and reproductive hormones all found significant
associations with at least one reproductive hormone; however, no consistent
relationships were observed across studies. Six epidemiologic studies evaluated
the relation between BPA and semen parameters, and although the majority reported
negative associations with various parameters, there were few consistent trends
across studies. Finally, three epidemiologic studies examined BPA and couple
reproductive outcomes, and only one found an association. Overall, the evidence
supporting an association between BPA exposure and adverse male reproductive
health outcomes in humans remains limited and inconclusive. Reasons for the
discrepancies in results could include, but are not limited to, differences in
study populations (e.g., fertile vs. subfertile men), BPA urinary concentrations
(occupationally vs. nonoccupationally exposed), misclassification of BPA exposure
(e.g., using one urine sample to characterize exposure vs. multiple samples),
sample sizes, study design (e.g., cross-sectional vs. prospective), and residual
confounding (e.g., due to diet and lifestyle factors). It is also possible that
some of the statistically significant findings were due to chance alone. Clearly,
further studies are needed to further clarify the role of this ubiquitous
endocrine-disrupting chemical on male reproductive health.
PMID- 27498137
TI - delta-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of
cardiac parasympathetic control and plasticity.
AB - BACKGROUND: Intermittent hypoxia training (IHT) produces robust myocardial
protection against ischemia-reperfusion induced infarction and arrhythmias.
Blockade of this cardioprotection by antagonism of either beta1-adrenergic or
delta-opioid receptors (delta-OR) suggests autonomic and/or opioidergic
adaptations. PURPOSE: To test the hypothesis that IHT shifts cardiac autonomic
balance toward greater cholinergic and opioidergic influence. METHODS: Mongrel
dogs completed 20d IHT, non-hypoxic sham training, or IHT with the delta-OR
antagonist naltrindole (200MUg/kgsc). The vagolytic effect of the delta-OR
agonist met-enkephalin-arg-phe delivered by sinoatrial microdialysis was
evaluated following IHT. Sinoatrial, atrial and left ventricular biopsies were
analyzed for changes in delta-OR, the neurotrophic monosialoganglioside, GM-1,
and cholinergic and adrenergic markers. RESULTS: IHT enhanced vagal bradycardia
vs. sham dogs (P<0.05), and blunted the delta2-OR mediated vagolytic effect of
met-enkephalin-arg-phe. The GM-1 labeled fibers overlapped strongly with
cholinergic markers, and IHT increased the intensity of both signals (P<0.05).
IHT increased low and high intensity vesicular acetylcholine transporter labeling
of sinoatrial nodal fibers (P<0.05) suggesting an increase in parasympathetic
arborization. IHT reduced select delta-OR labeled fibers in both the atria and
sinoatrial node (P<0.05) consistent with moderation of the vagolytic delta2-OR
signaling described above. Furthermore, blockade of delta-OR signaling with
naltrindole during IHT increased the protein content of delta-OR (atria and
ventricle) and vesicular acetylcholine transporter (atria) vs. sham and untreated
IHT groups. IHT also reduced the sympathetic marker, tyrosine hydroxylase in
ventricle (P<0.05). SUMMARY: IHT shifts cardiac autonomic balance in favor of
parasympathetic control via adaptations in opioidergic, ganglioside, and
adrenergic systems.
PMID- 27498138
TI - Genetic variants in RNA-induced silencing complex genes and prostate cancer.
AB - PURPOSE: The purpose of this study is to evaluate the potential association
between genetic variants in genes encoding the components of RNA-induced
silencing complex and prostate cancer (PCa) risk. Genetic variants chosen for
this study are rs3742330 in DICER1, rs4961280 in AGO2, rs784567 in TARBP2, rs7813
in GEMIN4 and rs197414 in GEMIN3. METHODS: The study involved 355 PCa patients,
360 patients with benign prostatic hyperplasia and 318 healthy controls. For
individuals diagnosed with PCa, clinicopathological characteristics including
serum prostate-specific antigen level at diagnosis, Gleason score (GS) and
clinical stage were determined. Genotyping was performed using high-resolution
melting analysis, PCR-RFLP, TaqMan SNP Genotyping Assay and real-time PCR-based
genotyping assay using specific probes. Allelic and genotypic associations were
evaluated by unconditional linear and logistic regression methods. RESULTS: The
study provided no evidence of association between the analyzed genetic variants
and PCa risk. Nevertheless, allele A of rs784567 was found to confer the reduced
risk of higher serum PSA level at diagnosis (P = 0.046; Difference = -66.64, 95 %
CI -131.93 to 1.35, for log-additive model). Furthermore, rs4961280, as well as
rs3742330, were shown to be associated with GS. These variants, together with
rs7813, were found to be associated with the lower clinical stage of PCa. Also,
rs3742330 minor allele G was found to be associated with lower PCa aggressiveness
(P = 0.036; OR 0.14, 95 % CI 0.023-1.22, for recessive model). CONCLUSIONS:
According to our data, rs3742330, rs4961280 and rs7813 qualify for potentially
protective genetic variants against PCa progression. These variants were not
shown to be associated with PCa risk.
PMID- 27498139
TI - Partial nephrectomy versus ablative therapy for the treatment of renal tumors in
an imperative setting.
AB - PURPOSE: To compare partial nephrectomy (PN) and percutaneous ablative therapy
(AT) for renal tumor in imperative indication of nephron-sparing technique (NST).
MATERIALS AND METHODS: Between 2000 and 2015, 284 consecutive patients with a
kidney tumor in an imperative indication of NST were retrospectively included in
a multicenter study. PN [open (n = 146), laparoscopic (n = 9), or robotic
approach (n = 17)] and AT [radiofrequency ablation (n = 104) or cryoablation (n =
8)] were performed for solitary kidney (n = 146), bilateral tumor (n = 78), or
chronic kidney disease (CKD) (n = 60). RESULTS: Patients in the PN group had
larger tumors and a higher RENAL score. There were no differences between the two
groups with respect to age, reasons for imperative indication, and preoperative
eGFR. Patients in the AT group had a higher ASA and CCI. PN had worse outcomes
than AT in terms of transfusion rate, length of stay, and complication rate.
Local radiological recurrence-free survival was better for PN, but metastatic
recurrence was similar. Percentage of eGFR decrease was similar in the two
groups. Temporary or permanent dialysis was not significantly different. On
multivariate analysis, PN and AT had a similar eGFR change when adjusted for
tumor complexity, reason of imperative indication and CCI. CONCLUSION: In
imperative indication of nephron-sparing treatment for a kidney tumor, either PN
or AT can be proposed. PN offers the ability to manage larger and more complex
tumors while providing a better local control and a similar renal function loss.
PMID- 27498140
TI - Cancer in Europe: Death sentence or life sentence?
AB - With so many adults and children receiving successful treatment for their cancer,
survivorship is now a 'new' and critical issue. It is increasingly recognised
that the growing numbers of survivors face new challenges in their bid to return
to 'normal' life. What is not yet so widely recognised is the need for a broad
response to help them cope-with stigmatisation, misunderstanding, lifelong issues
of confidence and social adaptation, and even access to employment and to
financial services. As a further stage in its programme of attention to this
aspect of cancer, the European Organisation for Research and Treatment of Cancer
(EORTC) brought survivors, researchers, carers, authorities and policymakers
together at a meeting in Brussels in March/April 2016, to learn at first hand
about the posttreatment experience of cancer survivors. The meeting demonstrated
that while research is well advanced in many of the medical consequences of
survivorship, understanding is still lacking of many non-clinical, personal and
administrative issues. The meeting raised the discussion of survivorship research
beyond the individual to a population-based approach, exploring the related
socioeconomic issues. Its exploration of initiatives across Europe countries
provoked new thinking on the need for effective collaboration, with a new focus
on non-clinical issues, including effective dialogue with financial service
providers and employers, improvements in collecting, exchanging and accessing
data, and above all, ways of translating research outcomes into action. This will
require wider recognition that, as Francoise Meunier, Director Special Projects,
EORTC, said, 'It is time for a new mind set'.
PMID- 27498141
TI - GNAQ and GNA11 mutations occur in 9.5% of mucosal melanoma and are associated
with poor prognosis.
AB - BACKGROUND: Mucosal melanoma (MM) is a rare subtype of melanoma in Caucasians
with extremely poor prognosis, and therapy strategy has not been clearly
established for MM. We aimed to investigate the genetic aberrations possibly
applicable in targeted therapy of MM. We examined the somatic mutations of GNAQ
and GNA11 (GNAQ/11, encoding the guanine nucleotide-binding alpha subunits) in MM
and evaluated their correlation to clinicopathologic features of MM. METHODS:
This study collected samples from primary lesions of 284 MM patients. Tissue
samples were analysed for mutations in exons 4 and 5 of GNAQ/11 in genomic DNA by
polymerase chain reaction amplification and Sanger sequencing. Correlations of
GNAQ/11 mutations to clinicopathologic features and prognosis of MM were
evaluated. RESULTS: The overall mutation frequency of GNAQ/11 in MM was 9.5% (27
in 284), with a frequency of 4.6% and 4.9% for GNAQ and GNA11 mutations,
respectively. The mutations in exon 5 of GNAQ/11 occurred exclusively in codon
209. GNAQ(Q209L) was the most prevalent variation (92.3% of missense GNAQ
mutations). GNAQ/11 mutations were not significantly associated with age, gender,
ulceration, and primary anatomic site. The median overall survival for MM
patients with GNAQ mutations (16.0 versus 26.0 months, P = 0.031) or GNA11
mutations (15.0 versus 26.0 months, P = 0.039) were significantly shorter than
those for patients with wild-type GNAQ and GNA11, respectively. CONCLUSIONS: Our
study suggests that GNAQ and GNA11 mutations occur frequently in MM and may be a
prognostic factor for MM. Our data implicate that GNAQ/11 may be potential
targets for targeted therapy of MM.
PMID- 27498142
TI - Oral pirfenidone protects against fibrosis by inhibiting fibroblast proliferation
and TGF-beta signaling in a murine colitis model.
AB - Inflammatory bowel disease (IBD), particularly Crohn's disease, frequently causes
intestinal fibrosis that ultimately leads to formation of strictures requiring
bowel resection. Currently there is no effective antifibrotic therapy available
for this disease. Pirfenidone is a small compound that has a broad spectrum of
antifibrogenic effect and has been used for the treatment of fibrotic diseases in
various organs. The present study aimed to investigate the antifibrogenic effect
of pirfenidone in a dextran sulfate sodium (DSS)-induced murine colitis model.
C57BL/6 mice were used and animals were randomly divided into groups receiving
pirfenidone or vehicle by oral or transanal routes. Inflammation- and fibrosis
related indexes including body weight, colon length, disease activity,
histological change, mRNA expression of pro-inflammatory and pro-fibrogenic
cytokines were assessed. Furthermore, we performed in vitro analysis using CCD18
Co fibroblasts to evaluate cell proliferation, transdifferentiation, and
viability after the cells were cultured with pirfenidone. It was found that oral
administration of pirfenidone reduced deposition of collagen in colitis
associated fibrosis, and significantly suppressed the mRNA expression of col1a2,
col3a1, and TGF-beta. Moreover, pirfenidone inhibited the activation of TGF-beta
related smad and MAPK pathways both in vitro and in vivo. Clinical and
histological evaluation demonstrated that pirfenidone had no anti-inflammatory
effect. The antifibrogenic effect was reduced when pirfenidone was administered
in a delayed manner and was unobserved if given locally. Pirfenidone suppressed
fibroblast proliferation and transdifferentiation without observed toxicity.
Altogether, our results suggested that oral pirfenidone protects against fibrosis
of DSS-induced colitis through inhibiting the proliferation of colonic
fibroblasts and TGF-beta signaling pathways.
PMID- 27498143
TI - Metabolism and gas exchange patterns in Rhodnius prolixus.
AB - Insect's metabolic rate and patterns of gas-exchange varies according to
different factors such as: species, activity, mass, and temperature among others.
One particular striking pattern of gas-exchange in insects is discontinuous gas
exchange cycles, for which many different hypotheses regarding their evolution
have been stated. This article does not pretend to be an extensive review on the
subject, rather to focus on the work performed on the haematophagous bug Rhodnius
prolixus, a model organism used from the mid XX century until present days, with
the great influence of Wigglesworth and his students/collaborator's work. I have
no doubt that the renovated field of insect gas-exchange has a bright future and
will advance at large gaits thank to the help of this model organism, R.
prolixus, whose entire genome has recently being unraveled.
PMID- 27498144
TI - Sclerotised spines in the female bursa associated with male's spermatophore
production in cantharidin-producing false blister beetles.
AB - Cantharidin is a defence chemical synthesised in only two beetle families
Meloidae and Oedemeridae. In Meloidae, cantharidin is used as a defence chemical
in eggs. However, in Oedemeridae the function of cantharidin remains unclear.
Based on morphological comparison of female internal reproductive organs in 39
species of Oedemeridae, we found that some species have sclerotised spines in the
bursa copulatrix (bursal spines), while others have no such spines. Molecular
phylogenetic trees inferred from mitochondrial 16S and nuclear 28S rRNA gene
sequences suggested multiple evolutionary origins of bursal spines from an
ancestor without spines. In the species which lacked spines, males transferred
small amounts of ejaculates to females; however, in species with spines, males
transferred large spermatophores. Deposited spermatophores gradually disappeared
in the bursa, probably owing to absorption. To compare the amounts of cantharidin
in eggs laid by species with and without bursal spines, we constructed a new
bioassay system using the small beetle Mecynotarsus tenuipes from the family
Anthicidae. M. tenuipes individuals were attracted to droplets of
cantharidin/acetone solution, and the level of attraction increased with
cantharidin concentration. This bioassay demonstrated that the eggs of Nacerdes
caudata and N. katoi, both of which species have conspicuous bursal spines,
contain more cantharidin than the eggs of N. waterhousei, which lacks spines. In
the former species, males transfer large spermatophores to the female, and
spermatophores are eventually broken down and digested within the female's spiny
bursa. Thus, females with bursal spines may be able to provide more cantharidin
to their eggs.
PMID- 27498145
TI - Early effects of Abeta1-42 oligomers injection in mice: Involvement of
PI3K/Akt/GSK3 and MAPK/ERK1/2 pathways.
AB - Neuronal and synaptic loss are the best pathological correlates for memory
decline in Alzheimer's disease (AD). Soluble beta-amyloid oligomers (AbetaO) are
considered to putatively play a crucial role in the early synapse loss and
cognitive impairment observed in AD. Evidence suggests that oxidative stress and
apoptosis are involved in the mechanism of Abeta-induced neurotoxicity and AD
pathogenesis. This study aimed to explore the molecular mechanisms that
contribute to the early memory deficits induced by intracerebroventricular
injection of AbetaO in mice. Ten days after a single AbetaO injection memory
impairments were observed, as measured by Morris water maze and novel object
recognition tests. Cognitive decline was associated with increased oxidative
stress, caspase-9 activation, and decreased hippocampal synaptophysin
immunoreactivity. Furthermore, GSH levels were significantly higher in AbetaO
injected mice than in sham mice, showing that a protective mechanism might
develop due to oxidative stress. Additionally, AbetaO-induced toxicity was
aligned with an increment of the activation of Akt and ERK1/2, and reduced
activity of GSK3. These findings suggest that AbetaO injection triggers a cascade
of events that mimic the key neuropathological hallmarks of AD. Abeta acute
injection helps to better understand how this peptide impairs specific signaling
pathways leading to synaptic and memory dysfunctions. Thus, this model is a valid
tool for investigating AD and may suggest a new way to develop neuroprotective
therapies at such early stages of the disease.
PMID- 27498146
TI - GC-MS-based metabolomic study on the antidepressant-like effects of diterpene
ginkgolides in mouse hippocampus.
AB - Ginkgo biloba extract (GBE), including EGb-761, have been suggested to have
antidepressant activity based on previous behavioral and biochemical analyses.
However, because GBE contain many constituents, the mechanisms underlying this
suggested antidepressant activity are unclear. Here, we investigated the
antidepressant-like effects of diterpene ginkgolides (DG), an important class of
constituents in GBE, and studied their effects in the mouse hippocampus using a
GC-MS-based metabolomics approach. Mice were randomly divided into five groups
and injected daily until testing with 0.9% NaCl solution, one of three doses of
DG (4.06, 12.18, and 36.54mg/kg), or venlafaxine. Sucrose preference (SPT) and
tail suspension (TST) tests were then performed to evaluate depressive-like
behaviors in mice. DG (12.18 and 36.54mg/kg) and venlafaxine (VLX) administration
significantly increased hedonic behavior in mice in the SPT. DG (12.18mg/kg)
treatment also shortened immobility time in the TST, suggestive of antidepressant
like effects. Significant differences in the metabolic profile in the DG
(12.18mg/kg) compared with the control or VLX group indicative of an
antidepressant-like effect were observed using multivariate analysis. Eighteen
differential hippocampal metabolites were identified that discriminated the DG
(12.18mg/kg) and control groups. These biochemical changes involved
neurotransmitter metabolism, oxidative stress, glutathione metabolism, lipid
metabolism, energy metabolism, and kynurenic acid, providing clues to the
therapeutic mechanisms of DG. Thus, this study showed that DG has antidepressant
like activities in mice and shed light on the biological mechanisms underlying
the effects of diterpene ginkgolides on behavior, providing an important drug
candidate for the treatment of depression.
PMID- 27498147
TI - Telencephalic neural activation following passive avoidance learning in a
terrestrial toad.
AB - The present study explores passive avoidance learning and its neural basis in
toads (Rhinella arenarum). In Experiment 1, two groups of toads learned to move
from a lighted compartment into a dark compartment. After responding, animals in
the experimental condition were exposed to an 800-mM strongly hypertonic NaCl
solution that leads to weight loss. Control animals received exposure to a 300-mM
slightly hypertonic NaCl solution that leads to neither weight gain nor loss.
After 10 daily acquisition trials, animals in the experimental group showed
significantly longer latency to enter the dark compartment. Additionally, 10
daily trials in which both groups received the 300-mM NaCl solution after
responding eliminated this group effect. Thus, experimental animals showed
gradual acquisition and extinction of a passive avoidance respond. Experiment 2
replicated the gradual acquisition effect, but, after the last trial, animals
were sacrificed and neural activation was assessed in five brain regions using
AgNOR staining for nucleoli-an index of brain activity. Higher activation in the
experimental animals, relative to controls, was observed in the amygdala and
striatum. Group differences in two other regions, lateral pallium and septum,
were borderline, but nonsignificant, whereas group differences in the medial
pallium were nonsignificant. These preliminary results suggest that a striatal
amygdala activation could be a key component of the brain circuit controlling
passive avoidance learning in amphibians. The results are discussed in relation
to the results of analogous experiments with other vertebrates.
PMID- 27498148
TI - Effects of environmental enrichment on anxiety-like behavior, sociability,
sensory gating, and spatial learning in male and female C57BL/6J mice.
AB - The influence of housing on cognition and emotional regulation in mice presents a
problem for the study of genetic and environmental risk factors for
neuropsychiatric disorders: standard laboratory housing may result in low levels
of cognitive function or altered levels of anxiety that leave little room for
assessment of deleterious effects of experimental manipulations. The use of
enriched environment (EE) may allow for the measurement of a wider range of
performance in cognitive domains. Cognitive and behavioral effects of EE in male
mice have not been widely reproduced, perhaps due to variability in the
application of enrichment protocols, and the effects of EE in female mice have
not been widely studied. We have developed an EE protocol using common laboratory
equipment that, without a running wheel for exercise, results in significant
cognitive and behavioral effects relative to standard laboratory housing
conditions. We compared male and female wild-type C57BL/6J mice reared from
weaning age in an EE to those reared in a standard environment (SE), using common
measures of anxiety-like behavior, sensory gating, sociability, and spatial
learning and memory. Sex was a significant factor in relevant elevated plus maze
(EPM) measures, and bordered on significance in a social interaction (SI) assay.
Effects of EE on anxiety-like behavior and sociability were indicative of a
general increase in exploratory activity. In male and female mice, EE resulted in
reduced prepulse inhibition (PPI) of the acoustic startle response, and enhanced
spatial learning and use of spatially precise strategies in a Morris water maze
task.
PMID- 27498149
TI - A Raf kinase inhibitor demonstrates antiviral activities both in vitro and in
vivo against different genotypes of virulent Newcastle disease virus.
AB - Newcastle disease (ND) is still one of the major plagues of birds worldwide.
Combat actions are limited to vaccines, highlighting the urgent need for new and
amply available antiviral drugs. Previous results have shown that Newcastle
disease virus (NDV) downregulates the intracellular Raf kinase inhibitor protein
(RKIP) expression for efficient replication, suggesting that this molecular may
be a suitable target for antiviral intervention. In the present work, we
investigated whether or not the Raf kinase inhibitor V (RKIV), which functions in
the same way as RKIP by targeting the intracellular Raf kinase, is able to
suppress the propagation of enzootic virulent NDV in vitro and in vivo. In vitro
antiviral activity of RKIV was assessed by cell-based assay, and in vivo activity
was determined in the chicken model. Our results clearly showed that RKIV
treatment protected the cells from NDV-induced CPE with the effective
concentrations on nM level, and inhibited virus replication in the lungs of
infected chickens in a dose-dependent manner and protected chickens from the
lethal infection by NDV. Thus, we conclude that the Raf kinase inhibitor compound
RKIV, by inhibiting the host cellular target Raf kinase, might be very promising
as a new class of antivirals against the enzootic virulent NDV infection.
PMID- 27498150
TI - Are nestin-positive mesenchymal stromal cells a better source of cells for CNS
repair?
AB - In recent years there has been a great deal of research within the stem cell
field which has led to the definition and classification of a range of stem cells
from a plethora of tissues and organs. Stem cells, by classification, are
considered to be pluri- or multipotent and have both self-renewal and multi
differentiation capabilities. Presently there is a great deal of interest in stem
cells isolated from both embryonic and adult tissues in the hope they hold the
therapeutic key to restoring or treating damaged cells in a number of central
nervous system (CNS) disorders. In this review we will discuss the role of
mesenchymal stromal cells (MSCs) isolated from human olfactory mucosa, with
particular emphasis on their potential role as a candidate for transplant
mediated repair in the CNS. Since nestin expression defines the entire population
of olfactory mucosal derived MSCs, we will compare these cells to a population of
neural crest derived nestin positive population of bone marrow-MSCs.
PMID- 27498151
TI - Long telomeres and cancer risk among 95 568 individuals from the general
population.
AB - BACKGROUND: Results regarding telomere length and cancer risk are conflicting. We
tested the hypothesis that long telomeres are associated with increased risk of
any cancer and specific cancer types in genetic and observational analyses.
METHODS: Individuals (N = 95 568) from the Copenhagen City Heart Study and the
Copenhagen General Population Study had the telomere length-associated genotypes
rs7726159 (TERT), rs1317082 (TERC), and rs2487999 (OBFC1) determined, and 65 176
had telomere length measured. A total of 10 895 individuals had had a cancer
diagnosis. Endpoints were any cancer and 25 specific cancer types. We conducted
Cox regression analyses and logistic regression analyses. The three genotypes
were combined as an allele sum. RESULTS: Telomere length increased 67 base-pairs
[95% confidence interval (CI) 61-74] per allele. In logistic regression models,
the per-allele odds ratio (OR) for cancer was 1.05 (95% CI 1.03-1.07) for the
allele sum, 1.05 (1.02-1.09) for rs7726159, 1.05 (1.02-1.08) for rs1317082 and
1.07 (1.02-1.12) for rs2487999. In contrast, the hazard ratio for any cancer was
1.01 (1.00-1.01) per 200-base-pair increase in telomere length in multivariable
adjusted observational analysis. In genetic analyses according to specific cancer
types, the per-allele odds ratio was 1.19 (1.12-1.27) for melanoma and 1.14 (1.06
1.22) for lung cancer. CONCLUSIONS: Genetic determinants of long telomeres are
associated with increased cancer risk, particularly melanoma and lung cancer.
This genetic predisposition to enhanced telomere maintenance may represent a
survival advantage for pre-cancerous cells, allowing for multiple cell divisions
leading to cancer development.
PMID- 27498152
TI - Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin
cohort.
AB - BACKGROUND: Current epigenetic studies on aging are dominated by the cross
sectional design that correlates subjects' ages or age groups with their measured
epigenetic profiles. Such studies have been more aimed at age prediction or
building up the epigenetic clock of age rather than focusing on the dynamic
patterns in epigenetic changes during the aging process. METHODS: We performed an
epigenome-wide association study of intra-individual longitudinal changes in DNA
methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood
samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake
73-82 years). Biological pathway analysis and survival analysis were also
conducted on CpGs showing longitudinal change in their DNA-methylation levels.
Classical twin models were fitted to each CpG site to estimate the genetic and
environmental effects on DNA-methylation. RESULTS: Our analysis identified 2284
CpG sites whose DNA-methylation levels changed longitudinally over the follow-up.
Twin modelling revealed that the longitudinal change for 90% of these CpG sites
was explained solely by individual unique environmental factors and only for 10%
of these sites was it influenced by familial factors (genetic or shared
environment). Over 60% of the identified CpG sites were replicated (same
direction and replication P < 0.05) in an independent cross-sectional sample of
300 twins aged from 30 to 74 years. The replication rate went up to 91% for the
top 53 CpGs with P < 1 * 10-07. Pathway analysis of genes linked to these CpGs
identified biologically meaningful gene-sets involved in cellular-signalling
events and in transmission across chemical synapses, which are important
molecular underpinnings of aging-related degenerative disorders. CONCLUSION: Our
epigenome-wide association studies on a cohort of old twins followed up for 10
years identified highly replicable epigenetic biomarkers predominantly implicated
in signalling pathways of degenerative disorders and survival in the elderly.
PMID- 27498153
TI - Verbal memory and search speed in early midlife are associated with mortality
over 25 years' follow-up, independently of health status and early life factors:
a British birth cohort study.
AB - BACKGROUND: Cognitive capabilities in childhood and in late life are inversely
associated with mortality rates. However, it is unclear if adult cognition, at a
time still relatively free from comorbidity, is associated with subsequent
mortality, and whether this explains the associations of early life factors with
adult mortality. METHODS: We used data from the MRC National Survey of Health and
Development, a birth cohort study prospectively assessing 5362 participants born
in 1946. The present analysis includes participants followed up from age 43 and
undergoing cognitive assessment (verbal memory and search speed). Mortality
outcomes were notified through linkage with a national register. Cox regression
was used to estimate mortality hazards in relation to cognitive performance at
age 43, adjusting for early life factors, socioeconomic position and health
status. RESULTS: Data were available on 3192 individuals. Univariable analyses
indicated that adult verbal memory and search speed, parental factors, childhood
cognition and educational attainment were associated with mortality. However,
multivariable models showed that the mortality associations with earlier life
factors were explained by adult cognitive capability. A standard deviation
increase in verbal memory and search speed scores was associated with lower
mortality rates [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.77
0.97, P = 0.02; HR = 0.88, 95% CI 0.78-1.00, P = 0.05, respectively), after
adjustment for adult health. CONCLUSIONS: Cognitive capability in early midlife
was inversely associated with mortality rates over 25 years and accounted for the
associations of family background, childhood cognitive ability and educational
attainment with mortality. These findings, in a nationally representative cohort
with long-term follow-up, suggest that building cognitive reserve may improve
later life health and survival chances.
PMID- 27498154
TI - Psychotic experiences in the context of depression: The cumulative role of
victimization.
AB - Previous studies have reported an association between depression and psychotic
experiences, but little is known about what drives this co-occurrence. This study
tests the hypothesis that exposure to trauma and bullying may strengthen the
relation between depression and psychotic experiences. A total of 799 college
students completed self-report questionnaires on psychotic experiences,
depression, bullying, and sexual trauma. Hierarchical linear regression analyses
were conducted to test the direct relationship between depression and psychotic
experiences, as well as interactions. Approximately 20% of respondents reported a
history of being bullied, and 7% reported exposure to childhood sexual trauma.
There was a significant direct relationship between depression and psychotic
experiences. The association between depression and psychotic experiences was
significantly stronger among respondents who were victims of both bullying and
sexual violence compared to those who experienced either exposure alone, or who
were not exposed to either form of victimization. These findings suggest that
cumulative exposure to trauma and victimization may contribute to the co
occurrence of depression and psychotic experiences. History of victimization
should be assessed among individuals with depressive symptoms to improve
treatment plans and outcomes.
PMID- 27498155
TI - Pure Delta9-tetrahydrocannabivarin and a Cannabis sativa extract with high
content in Delta9-tetrahydrocannabivarin inhibit nitrite production in murine
peritoneal macrophages.
AB - Historical and scientific evidence suggests that Cannabis use has
immunomodulatory and anti-inflammatory effects. We have here investigated the
effect of the non-psychotropic phytocannabinoid Delta9-tetrahydrocannabivarin
(THCV) and of a Cannabis sativa extract with high (64.8%) content in THCV (THCV
BDS) on nitric oxide (NO) production, and on cannabinoid and transient receptor
potential (TRP) channel expression in lipopolysaccharide (LPS)-stimulated murine
peritoneal macrophages. THCV-BDS and THCV exhibited similar affinity in
radioligand binding assays for CB1 and CB2 receptors, and inhibited, via CB2 but
not CB1 cannabinoid receptors, nitrite production evoked by LPS in peritoneal
macrophages. THCV down-regulated the over-expression of inducible nitric oxide
synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin 1beta (IL-1beta)
proteins induced by LPS. Furthermore, THCV counteracted LPS-induced up-regulation
of CB1 receptors, without affecting the changes in CB2, TRPV2 or TRPV4 mRNA
expression caused by LPS. Other TRP channels, namely, TRPA1, TRPV1, TRPV3 and
TRPM8 were poorly expressed or undetectable in both unstimulated and LPS
challenged macrophages. It is concluded that THCV - via CB2 receptor activation -
inhibits nitrite production in macrophages. The effect of this phytocannabinoid
was associated with a down-regulation of CB1, but not CB2 or TRP channel mRNA
expression.
PMID- 27498156
TI - Timing and crosstalk of glucocorticoid signaling with cytokines,
neurotransmitters and growth factors.
AB - Glucocorticoid actions are tailored to the organs and cells responding thanks to
complex integration with ongoing signaling mediated by cytokines, hormones,
neurotransmitters, and growth factors. Disruption of: (1) the amount of signaling
molecules available locally; (2) the timing with other signaling pathways; (3)
the post-translational modifications on glucocorticoid receptors; and (4) the
receptors-interacting proteins within cellular organelles and functional
compartments, can modify the sensitivity and efficacy of glucocorticoid responses
with implications in physiology, diseases and treatments. Tissue sensitivity to
glucocorticoids is sustained by multiple systems that do not operate in
isolation. We take the example of the interplay between the glucocorticoid and
brain-derived neurotrophic factor signaling pathways to deconstruct context
dependent glucocorticoid responses that play key roles in physiology, diseases
and therapies.
PMID- 27498157
TI - Integrins in glioblastoma: Still an attractive target?
AB - Integrin-mediated signaling pathways have been found to promote the invasiveness
and survival of glioma cells by modifying the brain microenvironment to support
the formation of the tumoral niche. A variety of cells in the niche express
integrin receptors, including tumor-associated macrophages, fibroblasts,
endothelial cells and pericytes. In particular, RGD-binding integrins have been
demonstrated to have an important role in the epithelial-mesenchymal transition
process, considered the first step in the infiltration of tissue by cancer cells
and molecular markers of which have been found in glioma cells. In simultaneous
research, Small Molecule Integrin Antagonists (SMIA) yielded initially promising
results in in vitro and in vivo studies, leading to clinical trials to test their
safety and efficacy in combination with other anticancer drugs in the treatment
of several tumor types. The initially high expectations, especially because of
their antiangiogenic activity, which appeared to be a winning strategy against
GBM, were not confirmed and this cast serious doubts on the real benefits to be
gained from the use of SMIA for the treatment of cancer in humans. In this
review, we provide an overview of recent findings concerning the functional roles
of integrins, especially RGD-binding integrins, in the processes related to
glioma cells survival and brain tissue infiltration. These findings disclose a
new scenario in which recently developed SMIA might become useful tools to hinder
glioblastoma cell dissemination.
PMID- 27498158
TI - Pharmacogenetic predictors of toxicity to platinum based chemotherapy in non
small cell lung cancer patients.
AB - Platinum-based chemotherapy is the standard treatment for NSCLC patients with
EGFR wild-type, and as alternative to failure to EGFR inhibitors. However, this
treatment is aggressive and most patients experience grade 3-4 toxicities. ERCC1,
ERCC2, ERCC5, XRCC1, MDM2, ABCB1, MTHFR, MTR, SLC19A1, IL6 and IL16 gene
polymorphisms may contribute to individual variation in toxicity to chemotherapy.
The aim of this study was to evaluate the effect of these polymorphisms on
platinum-based chemotherapy in NSCLC patients. A prospective cohorts study was
conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR Real
Time with Taqman((r)) probes and sequencing. Patients with ERCC1 C118T-T allele
(p=0.00345; RR=26.05; CI95%=4.33, 515.77) and ERCC2 rs50872-CC genotype
(p=0.00291; RR=4.06; CI95%=1.66, 10.65) had higher risk of general toxicity for
platinum-based chemotherapy. ERCC2 Asp312Asn G-alelle, ABCB1 C1236T-TT and the
IL1B rs12621220-CT/TT genotypes conferred a higher risk to present multiple
adverse events. The subtype toxicity analysis also revealed that ERCC2 rs50872-CC
genotype (p=0.01562; OR=3.23; CI95%=1.29, 8.82) and IL16 rs7170924-T allele
(p=0.01007; OR=3.19; CI95%=1.35, 7.97) were associated with grade 3-4
hematological toxicity. We did not found the influence of ERCC1 C8092A, ERCC2
Lys751Gln, ERCC2 Asp312Asn, ERCC5 Asp1104His, XRCC1 Arg194Trp, MDM2 rs1690924,
ABCB1 C3435T, ABCB1 Ala893Ser/Thr, MTHFR A1298C, MTHFR C677T, IL1B rs1143623,
IL1B rs16944, and IL1B rs1143627 on platinum-based chemotherapy toxicity. In
conclusion, ERCC1 C118T, ERCC2 rs50872, ERCC2 Asp312Asn, ABCB1 C1236T, IL1B
rs12621220 and IL16 rs7170924 polymorphisms may substantially act as prognostic
factors in NSCLC patients treated with platinum-based chemotherapy.
PMID- 27498159
TI - Factors associated with self-rated health status in Southwestern Iran: a
population-based study.
AB - OBJECTIVE: This study aimed to reveal the relationship between self-rated health
(SRH) and objective health status in the general population in the Southwest of
Iran. STUDY DESIGN: A cross-sectional study. METHODS: Data were collected by face
to-face interview with 3554 residents, aged >=18 years, who were selected by
multistage sampling procedure. Collected data included sociodemographic, SRH
status, and medical conditions; chronic diseases and mental symptoms. SRH was
indicated by a single question in five scales of very good, good, fair, poor and
very poor. An ordinal logistic regression analysis was used. Independent
variables were organized into four blocks: block 1, age, gender, marital status,
education level, employment status, size of household and monthly household
income; block 2, chronic or long-term illness (coronary heart disease,
hypertension and diabetes mellitus); block 3, psychological disorders (anxiety,
impatience and sleep disorders); and block 4 (visual, skin, hearing and oral
disorders). RESULTS: SRH status in most subjects reported to be positive,
indicating 47.3% as very good, 30.8% good, 16.2% fair, 3.3% bad and 2.4% very
bad. In studied subjects, poorer SRH was significantly related to older age (odds
ratio [OR], 1.01), low-education level (OR, 1.09), single status (OR, 1.25),
monthly household income (OR, 1.21), more chronic or long-term illness (OR,
1.61), greater psychological health disorders (OR, 1.69), more dermatologic
disorders (OR, 1.30), and hearing problems (OR, 1.47). CONCLUSION: Results of
this study revealed that subjects with worse SRH were older with low-education
level, lower household monthly income, more chronic illness, greater
psychological health disorders, and more visual, skin, hearing and oral
disorders. So, SRH, as indicated globally, can be used as a population screening
tool to identify subjects who are most in need of public health services.
PMID- 27498160
TI - Reply.
PMID- 27498161
TI - A nonlinear control scheme based on dynamic evolution path theory for improved
dynamic performance of boost PFC converter working on nonlinear features.
AB - This paper is concerned to performance improvement of boost PFC converter under
large random load fluctuation, ensuring unity power factor (UPF) at source end
and regulated voltage at load side. To obtain such performance, a nonlinear
controller based on dynamic evolution path theory is designed and its robustness
is examined under both heavy and light loading condition. In this paper, %THD and
zero-cross-over dead-zone of input current is significantly reduced. Also, very
less response time of input current and output voltage to that of load and
reference variation is remarked. A simulation model of proposed system is
designed and it is realized using dSPACE 1104 signal processor for a 390VDC, 500W
prototype. The relevant experimental and simulation waveforms are presented.
PMID- 27498162
TI - Finite-time synchronization for second-order nonlinear multi-agent system via
pinning exponent sliding mode control.
AB - In this paper we investigate the finite-time synchronization for second-order
multi-agent system via pinning exponent sliding mode control. Firstly, for the
nonlinear multi-agent system, differential mean value theorem is employed to
transfer the nonlinear system into linear system, then, by pinning only one node
in the system with novel exponent sliding mode control, we can achieve
synchronization in finite time. Secondly, considering the 3-DOF helicopter system
with nonlinear dynamics and disturbances, the novel exponent sliding mode control
protocol is applied to only one node to achieve the synchronization. Finally, the
simulation results show the effectiveness and the advantages of the proposed
method.
PMID- 27498163
TI - C-di-GMP Synthesis: Structural Aspects of Evolution, Catalysis and Regulation.
AB - Cellular levels of the second messenger cyclic di-guanosine monophosphate (c-di
GMP) are determined by the antagonistic activities of diguanylate cyclases and
specific phosphodiesterases. In a given bacterial organism, there are often
multiple variants of the two enzymes, which are tightly regulated by a variety of
external and internal cues due to the presence of specialized sensory or
regulatory domains. Dependent on the second messenger level, specific c-di-GMP
receptors then control fundamental cellular processes, such as bacterial life
style, biofilm formation, and cell cycle control. Here, I review the large body
of data on structure-function relationships in diguanylate cyclases. Although the
catalytic GGDEF domain is related to the respective domain of adenylate cyclases,
the catalyzed intermolecular condensation reaction of two GTP molecules requires
the formation of a competent GGDEF dimer with the two substrate molecules
juxtaposed. This prerequisite appears to constitute the basis for GGDEF
regulation with signal-induced changes within the homotypic dimer of the input
domain (PAS, GAF, HAMP, etc.), which are structurally coupled with the
arrangement of the GGDEF domains via a rigid coiled-coil linker. Alternatively,
phosphorylation of a Rec input domain can drive GGDEF dimerization. Both
mechanisms allow modular combination of input and output function that appears
advantageous for evolution and rationalizes the striking similarities in domain
architecture found in diguanylate cyclases and histidine kinases.
PMID- 27498164
TI - Contribution of Bistability and Noise to Cell Fate Transitions Determined by
Feedback Opening.
AB - Alternative cell fates represent a form of non-genetic diversity, which can
promote adaptation and functional specialization. It is difficult to predict the
rate of the transition between two cell fates due to the strong effect of noise
on feedback loops and missing parameters. We opened synthetic positive feedback
loops experimentally to obtain open-loop functions. These functions allowed us to
identify a deterministic model of bistability by bypassing noise and the
requirement to resolve individual processes in the loop. Combining the open-loop
function with kinetic measurements and reintroducing the measured noise, we were
able to predict the transition rates for the feedback systems without parameter
tuning. Noise in gene expression was the key determinant of the transition rates
inside the bistable range. Transitions between two cell fates were also observed
outside of the bistable range, evidenced by bimodality and hysteresis. In this
case, a slow transient process was the rate-limiting step in the transitions.
Thus, feedback opening is an effective approach to identify the determinants of
cell fate transitions and to predict their rates.
PMID- 27498165
TI - Compact Structure Patterns in Proteins.
AB - Globular proteins typically fold into tightly packed arrays of regular secondary
structures. We developed a model to approximate the compact parallel and
antiparallel arrangement of alpha-helices and beta-strands, enumerated all
possible topologies formed by up to five secondary structural elements (SSEs),
searched for their occurrence in spatial structures of proteins, and documented
their frequencies of occurrence in the PDB. The enumeration model grows larger
super-secondary structure patterns (SSPs) by combining pairs of smaller patterns,
a process that approximates a potential path of protein fold evolution. The most
prevalent SSPs are typically present in superfolds such as the Rossmann-like
fold, the ferredoxin-like fold, and the Greek key motif, whereas the less
frequent SSPs often possess uncommon structure features such as split beta
sheets, left-handed connections, and crossing loops. This complete SSP
enumeration model, for the first time, allows us to investigate which
theoretically possible SSPs are not observed in available protein structures. All
SSPs with up to four SSEs occurred in proteins. However, among the SSPs with five
SSEs, approximately 20% (218) are absent from existing folds. Of these unobserved
SSPs, 80% contain two or more uncommon structure features. To facilitate future
efforts in protein structure classification, engineering, and design, we provide
the resulting patterns and their frequency of occurrence in proteins at:
http://prodata.swmed.edu/ssps/.
PMID- 27498166
TI - Traction force dynamics predict gap formation in activated endothelium.
AB - In many pathological conditions the endothelium becomes activated and
dysfunctional, resulting in hyperpermeability and plasma leakage. No specific
therapies are available yet to control endothelial barrier function, which is
regulated by inter-endothelial junctions and the generation of acto-myosin-based
contractile forces in the context of cell-cell and cell-matrix interactions.
However, the spatiotemporal distribution and stimulus-induced reorganization of
these integral forces remain largely unknown. Traction force microscopy of human
endothelial monolayers was used to visualize contractile forces in resting cells
and during thrombin-induced hyperpermeability. Simultaneously, information about
endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F
actin) were captured. This revealed a heterogeneous distribution of traction
forces, with nuclear areas showing lower and cell-cell junctions higher traction
forces than the whole-monolayer average. Moreover, junctional forces were
asymmetrically distributed among neighboring cells. Force vector orientation
analysis showed a good correlation with the alignment of F-actin and revealed
contractile forces in newly formed filopodia and lamellipodia-like protrusions
within the monolayer. Finally, unstable areas, showing high force fluctuations
within the monolayer were prone to form inter-endothelial gaps upon stimulation
with thrombin. To conclude, contractile traction forces are heterogeneously
distributed within endothelial monolayers and force instability, rather than
force magnitude, predicts the stimulus-induced formation of intercellular gaps.
PMID- 27498167
TI - Primary Health Care: Potential Home for Family-Focused Preventive Interventions.
AB - Family-focused prevention programs have been shown to effectively reduce a range
of negative behavioral health outcomes but have had limited reach. Three key
barriers must be overcome to expand the reach of family-focused prevention
programs and thereby achieve a significant public health impact. These barriers
are (1) current social norms and perceptions of parenting programs; (2) concerns
about the expertise and legitimacy of sponsoring organizations to offer parenting
advice; and (3) a paucity of stable, sustainable funding mechanisms. Primary
healthcare settings are well positioned to overcome these barriers. Recent
changes within health care make primary care settings an increasingly favorable
home for family-focused prevention and suggest possibilities for sustainable
funding of family-focused prevention programs. This paper discusses the existing
advantages of primary care settings and lays out a plan to move toward realizing
the potential public health impact of family-focused prevention through
widespread implementation in primary healthcare settings.
PMID- 27498168
TI - Mycoextraction of radiolabeled cesium and strontium by Pleurotus eryngii mycelia
in the presence of alumina nanoparticles: Sorption and accumulation studies.
AB - Widespread use of products based on nanomaterials results in the release of
nanoparticles into the environment. Nanoparticles can be taken up by organisms,
but they can also coexist with other substances such as radionuclides, thus
affecting their uptake or toxicity. In contrast, the sorption capacity of
nanoparticles is exploited in water purification. The aim of the study was to
investigate: (i) bioaccumulation of cesium and strontium by Pleurotus eryngii
mycelia in the presence of alumina nanoparticles (Al2O3 NPs); and (ii) sorption
of radionuclides on the surface of nanoparticles. For the experiments, living and
dried mycelia were used to permit distinguishing between active uptake and
passive sorption of the NPs by P. eryngii. The results are discussed from the
perspective of the use of P. eryngii in the mycoextraction of radionuclides. The
sorption capacity of Al2O3 NPs and the accumulation by P. eryngii mycelia differ
for the applied radioisotopes. The efficiency of Cs and Sr sorption by alumina
nanoparticles is 20% and 40%, respectively. Mycelia of P. eryngii have the
ability to accumulate 30% of both radioisotopes from the medium. More than 60% of
strontium can be removed accumulated from water by P. eryngii mycelia in
coexistence with Al2O3 NPs, while the efficiency of cesium removal accumulation
is negligible. It was found that alumina nanoparticles do not enhance uptake of
radionuclides by P. eryngii mycelia; mycoextraction of radionuclides by mycelia
and sorption by Al2O3 NPs are concurrent processes. There was no difference
between live or dried mycelia uptake.
PMID- 27498170
TI - Carcinogenesis explained within the context of a theory of organisms.
AB - For a century, the somatic mutation theory (SMT) has been the prevalent theory to
explain carcinogenesis. According to the SMT, cancer is a cellular problem, and
thus, the level of organization where it should be studied is the cellular level.
Additionally, the SMT proposes that cancer is a problem of the control of cell
proliferation and assumes that proliferative quiescence is the default state of
cells in metazoa. In 1999, a competing theory, the tissue organization field
theory (TOFT), was proposed. In contraposition to the SMT, the TOFT posits that
cancer is a tissue-based disease whereby carcinogens (directly) and mutations in
the germ-line (indirectly) alter the normal interactions between the diverse
components of an organ, such as the stroma and its adjacent epithelium. The TOFT
explicitly acknowledges that the default state of all cells is proliferation with
variation and motility. When taking into consideration the principle of
organization, we posit that carcinogenesis can be explained as a relational
problem whereby release of the constraints created by cell interactions and the
physical forces generated by cellular agency lead cells within a tissue to regain
their default state of proliferation with variation and motility. Within this
perspective, what matters both in morphogenesis and carcinogenesis is not only
molecules, but also biophysical forces generated by cells and tissues. Herein, we
describe how the principles for a theory of organisms apply to the TOFT and thus
to the study of carcinogenesis.
PMID- 27498171
TI - Diversity in S-layers.
AB - Surface layers, referred simply as S-layers, are the two-dimensional crystalline
arrays of protein or glycoprotein subunits on cell surface. They are one of the
most common outermost envelope components observed in prokaryotic organisms
(Archaea and Bacteria). Over the past decades, S-layers have become an issue of
increasing interest due to their ubiquitousness, special features and functions.
Substantial work in this field provides evidences of an enormous diversity in S
layers. This paper reviews and illustrates the diversity from several different
aspects, involving the S-layer-carrying strains, the structure of S-layers, the S
layer proteins and genes, as well as the functions of S-layers.
PMID- 27498169
TI - Eukaryotic resectosomes: A single-molecule perspective.
AB - DNA double-strand breaks (DSBs) disrupt the physical and genetic continuity of
the genome. If unrepaired, DSBs can lead to cellular dysfunction and malignant
transformation. Homologous recombination (HR) is a universally conserved DSB
repair mechanism that employs the information in a sister chromatid to catalyze
error-free DSB repair. To initiate HR, cells assemble the resectosome: a multi
protein complex composed of helicases, nucleases, and regulatory proteins. The
resectosome nucleolytically degrades (resects) the free DNA ends for downstream
homologous recombination. Several decades of intense research have identified the
core resectosome components in eukaryotes, archaea, and bacteria. More recently,
these proteins have been characterized via single-molecule approaches. Here, we
focus on recent single-molecule studies that have begun to unravel how nucleases,
helicases, processivity factors, and other regulatory proteins dictate the extent
and efficiency of DNA resection in eukaryotic cells. We conclude with a
discussion of outstanding questions that can be addressed via single-molecule
approaches.
PMID- 27498172
TI - Measuring frailty in Dutch community-dwelling older people: Reference values of
the Tilburg Frailty Indicator (TFI).
AB - OBJECTIVES: The objectives of this study were to provide reference values of the
Tilburg Frailty Indicator (TFI) for community-dwelling older people by age, sex,
marital status, ethnicity, education, income, and residence, and examine the
effects of these seven socio-demographic variables on frailty. METHODS: 47,768
individuals aged 65 years and older living in the Netherlands completed a health
questionnaire (58.5% response rate), including the TFI. The TFI is a self-report
questionnaire for measuring frailty, developed from an integral approach of
frailty, including physical, psychological, and social domains. RESULTS:
Reference values were provided for men and women separately, as a function of
age. We found associations of all socio-demographic variables with frailty, also
after controlling for the effects of age. These associations held for both sexes
and for big cities as wells as more rural areas. For instance, the effect of age
was large for total and physical frailty, women were more frail than men, and
some very large average frailty differences between the ethnic groups were found,
with autochthon people having the lowest frailty score. CONCLUSIONS: In
conclusion, this study offers reference values of the TFI by socio-demographic
characteristics and explains frailty using these characteristics. This
information will support researchers, policymakers and health care professionals
in interpreting scores of the TFI, which may guide their efforts to reduce
frailty and its adverse outcomes.
PMID- 27498173
TI - Effects of Coaching and Repeated Trials on Maximum Phonational Frequency Range in
Children.
AB - PURPOSE: Maximum phonational frequency range (MPFR) is the frequency range from
the lowest to the highest pitch that an individual can produce. This study
investigated the effects of coaching and repeated trials on MPFR in a group of
school-age children. METHODS: Thirty girls aged 6-11 years were randomly assigned
into two groups: coaching and non-coaching. All of the participants produced the
lowest and the highest phonational frequency for 10 times each. The participants
in the coaching group were prompted by the clinician with verbal encouragement
and a visual cue (hand-sweeping) to produce their maximum performance. The
participants in the non-coaching group were simply asked to repeat the task 10
times. RESULTS: The clinician's coaching helped the participants in the coaching
group reach their MPFR in fewer trials. The MPFRs elicited in 10 trials were
significantly greater than those elicited in fewer trials. CONCLUSIONS: These
findings suggested that coaching and repeated trials could facilitate the
elicitation of MPFR more efficiently.
PMID- 27498174
TI - Prevalence of Voice Disorders in Iranian Primary School Students.
AB - OBJECTIVES: The voice is the sound produced by vibration of our vocal cords and
has an important role in verbal communication. A child's voice disorder may
significantly impair his or her ability to be heard and understood. The purpose
of this study was to determine the prevalence of voice disorders in primary
school students. METHODS AND MATERIALS: In this descriptive-analytical study, a
total of 501 fourth through fifth grade primary school students (boys = 51.6%,
girls = 48.4%) with the age range of 10-12 years were selected from nine public
school systems in Tehran that were assessed in October 2013 through March 2014.
Presence of a voice disorder characterized by hoarseness was identified by a dual
approach including investigator screening and parent identification. We used the
grade of overall dysphonia, roughness, breathiness, asthenia, and strain scale
for perceptual evaluation of voice. All children were assessed with video
laryngoscopy examination by an otorhinolaryngologist. The recordings were made
during spontaneous speech, counting numbers, sustained utterance of the (/a/)
vowel, reading a standard passage in Farsi, and the ratio of /s/ and /z/.
Statistical analysis was done via chi-square test and t test. RESULTS: Results
indicated that the prevalence of voice disorders in primary school students is
53.2%. The results indicated significant differences between gender and subjects
with lesions (P = 0.00000), gender and vocal disorders (P = 0.04), and s/z ratio
and type of lesion (P = 0.0002). CONCLUSION: Phonotrauma seems to play an
important role in child dysphonia, with nodules as main diagnosis.
PMID- 27498175
TI - Dental Morbidities, Smoking, Oral Hygiene, and Inflammatory Bowel Diseases.
PMID- 27498176
TI - Fecal Immunochemical Test Detects Sessile Serrated Adenomas and Polyps With a Low
Level of Sensitivity.
AB - BACKGROUND & AIMS: The serrated pathway is a distinct pathway of colorectal
carcinogenesis that has been implicated in development of a substantial
proportion of interval colorectal cancers. The fecal immunochemical test (FIT)
detects early neoplasms with a higher level of sensitivity than the guaiac test.
We investigated the sensitivity of the FIT in detection of sessile serrated
adenomas/polyps (SSA/Ps). METHODS: We performed a prospective study of 6198
asymptomatic subjects (mean age, 59.0 +/- 7.0 years) who received concurrent
screening colonoscopies and FITs at the Health Management Center of National
Taiwan University Hospital from August 2010 through November 2014. The
sensitivity of FIT for conventional adenoma, advanced adenoma, and SSA/P at
different cutoffs was calculated, and results were compared by using multivariate
analysis adjusted for potential confounders. RESULTS: Prevalence values of SSA/P,
adenoma, and advanced adenoma were 1.4%, 20.2%, and 5.5%, respectively. At
cutoffs of 10, 15, and 20 MUg hemoglobin/g feces, the FIT detected all SSA/Ps
with 12.3%, 6.2%, and 6.2% sensitivity, large SSA/Ps with 18.4%, 10.5%, and 10.5%
sensitivity, and advanced adenomas with 32.4%, 24.5%, and 20.9% sensitivity,
respectively. Multivariate analysis revealed that positive results from the FIT
did not differ significantly between individuals with SSA/P and those with non
advanced adenoma or those with negative findings from colonoscopy. Patients with
large SSA/Ps were less likely to have positive results from the FIT than patients
with advanced adenoma, with odds ratios of 0.44 (95% confidence interval [CI],
0.18-1.05), 0.30 (95% CI, 0.10-0.90), and 0.37 (95% CI, 0.12-1.12) at cutoffs of
10, 15, and 20 MUg hemoglobin/g feces, respectively, after adjusting for lesion
size, even with synchronous conventional adenoma. CONCLUSIONS: In a prospective
study of 6198 subjects receiving the FIT and colonoscopy, we found that the FIT
detected SSA/Ps with significantly lower levels of sensitivity than conventional
adenoma. Further studies are needed to determine the effects of these findings on
the effectiveness of FIT-based colorectal cancer screening program.
PMID- 27498177
TI - Inkjet printed periodical micropatterns made of inert alumina ceramics induce
contact guidance and stimulate osteogenic differentiation of mesenchymal stromal
cells.
AB - Bioinert high performance ceramics exhibit detrimental features for implant
components with direct bone contact because of their low osseointegrating
capability. We hypothesized that periodical microstructures made of inert alumina
ceramics can influence the osteogenic differentiation of human mesenchymal
stromal cells (hMSC). In this study, we manufactured pillared arrays made of
alumina ceramics with periodicities as low as 100MUm and pillar heights of 40MUm
employing direct inkjet printing (DIP) technique. The response of hMSC to the
microstructured surfaces was monitored by measuring cell morphology, viability
and formation of focal adhesion complexes. Osteogenic differentiation of hMSCs
was investigated by alkaline phosphatase activity, mineralization assays and
expression analysis of respective markers. We demonstrated that MSCs react to the
pillars with contact guidance. Subsequently, cells grow onto and form connections
between the microstructures, and at the same time are directly attached to the
pillars as shown by focal adhesion stainings. Cells build up tissue-like
constructs with heights up to the micropillars resulting in increased cell
viability and osteogenic differentiating properties. We conclude that periodical
micropatterns on the micrometer scale made of inert alumina ceramics can mediate
focal adhesion dependent cell adhesion and stimulate osteogenic differentiation
of hMSCs.
PMID- 27498179
TI - Pathogen-associated porin turns IL-10 competent B-1a cells toward proinflammatory
cytokine response.
AB - Shigellosis is a major problem in the developing countries causing mortality and
morbidity particularly among the children. Shigella spp. harbours the epithelial
cells of the human colon to infect the host and spread the disease. We analyzed
the response of B-1a cells, the major component of the mucosal immune system to
porin of Shigella dysenteriae type 1. We show that porin while proliferating B-1a
cells, deplete Siglec-G, the inhibitory molecule present on B-1a cells.
Adjuvanticity of porin has been shown to govern innate signaling for promoting
host adaptive immune response. Up-regulation of CD69 and CD40 denotes activation
of the cells parallel to abrogation of Siglec-G. As a result of cell activation,
porin stimulated the inflammatory cytokines of CD5+ B-1a cells, otherwise rich in
IL-10. The work shows B-1a cell responses promote the immunopotentiating activity
of porin.
PMID- 27498178
TI - Combinatorial extracellular matrix microenvironments promote survival and
phenotype of human induced pluripotent stem cell-derived endothelial cells in
hypoxia.
AB - Recent developments in cell therapy using human induced pluripotent stem cell
derived endothelial cells (iPSC-ECs) hold great promise for treating ischemic
cardiovascular tissues. However, poor post-transplantation viability largely
limits the potential of stem cell therapy. Although the extracellular matrix
(ECM) has become increasingly recognized as an important cell survival factor,
conventional approaches primarily rely on single ECMs for in vivo co-delivery
with cells, even though the endothelial basement membrane is comprised of a
milieu of different ECMs. To address this limitation, we developed a
combinatorial ECM microarray platform to simultaneously interrogate hundreds of
micro-scale multi-component chemical compositions of ECMs on iPSC-EC response.
After seeding iPSC-ECs onto ECM microarrays, we performed high-throughput
analysis of the effects of combinatorial ECMs on iPSC-EC survival, endothelial
phenotype, and nitric oxide production under conditions of hypoxia (1% O2) and
reduced nutrients (1% fetal bovine serum), as is present in ischemic injury
sites. Using automated image acquisition and analysis, we identified
combinatorial ECMs such as collagen IV+gelatin+heparan sulfate+laminin and
collagen IV+fibronectin+gelatin+heparan sulfate+laminin that significantly
improved cell survival, nitric oxide production, and CD31 phenotypic expression,
in comparison to single-component ECMs. These results were further validated in
conventional cell culture platforms and within three-dimensional scaffolds.
Furthermore, this approach revealed complex ECM interactions and non-intuitive
cell behavior that otherwise could not be easily determined using conventional
cell culture platforms. Together these data suggested that iPSC-EC delivery
within optimal combinatorial ECMs may improve their survival and function under
the condition of hypoxia with reduced nutrients. STATEMENT OF SIGNIFICANCE: Human
endothelial cells (ECs) derived from induced pluripotent stem cells (iPSC-ECs)
are promising for treating diseases associated with reduced nutrient and oxygen
supply like heart failure. However, diminished iPSC-EC survival after
implantation into diseased environments limits their therapeutic potential. Since
native ECs interact with numerous extracellular matrix (ECM) proteins for
functional maintenance, we hypothesized that combinatorial ECMs may improve cell
survival and function under conditions of reduced oxygen and nutrients. We
developed a high-throughput system for simultaneous screening of iPSC-ECs
cultured on multi-component ECM combinations under the condition of hypoxia and
reduced serum. Using automated image acquisition and analytical algorithms, we
identified combinatorial ECMs that significantly improved cell survival and
function, in comparison to single ECMs. Furthermore, this approach revealed
complex ECM interactions and non-intuitive cell behavior that otherwise could not
be easily determined.
PMID- 27498180
TI - Stress and binge drinking: A toxic combination for the teenage brain.
AB - Young adult university students frequently binge on alcohol and have high stress
levels. Based on findings in rodents, we predicted that heavy current alcohol use
and elevated stress and depression scores would be associated with deficits on
high interference memory tasks, while early onset, prolonged binge patterns would
lead to broader cognitive deficits on tests of associative encoding and executive
functions. We developed the Concentration Memory Task, a novel computerized
version of the Concentration card game with a high degree of interference. We
found that young adults with elevated stress, depression, and alcohol consumption
scores were impaired in the Concentration Memory Task. We also analyzed data from
a previous study, and found that higher alcohol consumption scores were
associated with impaired performance on another high interference memory task,
based on Kirwan and Stark's Mnemonic Similarity Test. On the other hand,
adolescent onset of binge drinking predicted poorer performance on broader range
of memory tests, including a more systematic test of spatial recognition memory,
and an associative learning task. Our results are broadly consistent with
findings in rodents that acute alcohol and stress exposure suppress neurogenesis
in the adult hippocampus, which in turn impairs performance in high interference
memory tasks, while adolescent onset binge drinking causes more extensive brain
damage and cognitive deficits.
PMID- 27498182
TI - How to manage central nervous system MRI with a cardiac implantable electronic
device?
PMID- 27498181
TI - Nonagonal cadherins: A new protein family found within the Stramenopiles.
AB - Cadherins, a group of molecules typically associated with planar cell polarity
and Wnt signalling, have been little reported outside of the animal kingdom.
Here, we identify a new family of cadherins in the Stramenopiles, termed
Nonagonal after their 9 transmembrane passes, which contrast to the one or seven
passes found in other known cadherin families. Manual curation and experimental
validation reveal two subclasses of nonagonal cadherins, depending on the number
of uninterrupted extracellular cadherin (EC) modules presented. Firstly, shorter
mono-exonic, unimodular, protein models, with 3 to 12 EC domains occur as
duplicate paralogs in the saprotrophic Labyrinthulomycetes Aurantiochytrium
limanicum and Schizochytrium aggregatum, the gastrointestinal Blastocystis
hominis (Blastocystae) and as a single copy gene in the autotrophic Pelagophyte
Aureococcus anophagefferens. Larger, single copy, multi-exonal, tri-modular
protein models, with up to 72 EC domain in total, are found in the Oomycete
genera Albugo, Phytophthora, Pythium and Eurychasma. No homolog was found in the
closely related autotrophic Phaeophyceae (brown algae) or Bacillariophyceae
(diatoms), nor in several genera of plant and animal pathogenic oomycetes
(Aphanomyces, Saprolegnia and Hyaloperonospora). This potential absence was
further investigated by synteny analysis of the genome regions flanking the
cadherin gene models, which are found to be highly variable. Novel to this new
cadherin family is the presence of intercalated laminin and putative carbohydrate
binding in tri-modular oomycete cadherins and at the N-terminus of
thraustochytrid proteins. As we were unable to detect any homologs of proteins
involved in signalling pathways where other cadherin families are involved, we
present a conceptual hypothesis on the function of nonagonal cadherin based
around the presence of putative carbohydrate binding domains.
PMID- 27498183
TI - Characterization of efficient plant-growth-promoting bacteria isolated from Sulla
coronaria resistant to cadmium and to other heavy metals.
AB - The inoculation of plants with plant-growth-promoting rhizobacteria has become a
priority in the phytoremediation of heavy-metal-contaminated soils. A total of 82
bacteria were isolated from Sulla coronaria root nodules cultivated on four soil
samples differently contaminated by heavy metals. The phenotypic characterization
of these isolates demonstrated an increased tolerance to cadmium reaching 4.1mM,
and to other metals, including Zn, Cu and Ni. Polymerase Chain
Reaction/Restriction Fragment Length Polymorphism (PCR/RFLP) analysis showed a
large diversity represented by genera related to Agrobacterium sp., R.
leguminosarum, Sinorhizobium sp., Pseudomonas sp., and Rhizobium sp. Their
symbiotic effectiveness was evaluated by nodulation tests. Taking into
consideration efficiency and cadmium tolerance, four isolates were chosen; their
16SrRNA gene sequence showed that they belonged to Pseudomonas sp. and the
Rhizobium sullae. The selected consortium of soil bacteria had the ability to
produce plant-growth-promoting substances such as indole acetic acid and
siderophore. The intracellular Cd accumulation was enhanced by increasing the
time of incubation of the four soil bacteria cultivated in a medium supplemented
with 0.1mM Cd. The existence of a cadmium-resistant gene was confirmed by PCR.
These results suggested that Sulla coronaria in symbiosis with the consortium of
plant-growth-promoting rhizobacteria (PGPR) could be useful in the
phytoremediation of cadmium-contaminated soils.
PMID- 27498184
TI - Tensions and conflicts in 'choice': Womens' experiences of freebirthing in the
UK.
AB - BACKGROUND: the concept of choice is a central tenet of modern maternity care.
However, in reality women's choice of birth is constrained by a paucity of
resources and dominant medical and risk adverse discourses. In this paper we add
to this debate through highlighting the tensions and conflicts that women faced
when enacting a freebirthing choice. METHODS: secondary analysis of data
collected to explore why women choose to freebirth in the UK was undertaken. Ten
women were recruited from diverse areas of the UK via invitations on freebirthing
websites. Women provided a narrative and/or participated in an in-depth
interview. A thematic analysis approach was used. FINDINGS: we present three key
themes. First 'violation of rights' highlights the conflicts women faced from
maternity care systems who were unaware of women's legal rights to freebirth,
conflating this choice with issues of child protection. 'Tactical planning'
describes some of the strategies women used in their attempts to achieve the
birth they desired and to circumnavigate any interference or reprisals. The third
theme, 'unfit to be a mother' describes distressing accounts of women who were
reported to social services. CONCLUSION AND IMPLICATIONS FOR PRACTICE: women who
choose to freebirth face opposition and conflict from maternity providers, and
often negative and distressing repercussions through statutory referrals. These
insights raise important implications for raising awareness among health
professionals about women's legal rights. They also emphasise a need to develop
guidelines and care pathways that accurately and sensitively support the midwives
professional scope of practice and women's choices for birth.
PMID- 27498185
TI - Education, employment and practice: Midwifery graduates in Papua New Guinea.
AB - BACKGROUND: Papua New Guinea has a very high maternal mortality rate
(773/100,000), low rates of supervised births and a critical shortage of skilled
midwives. A midwifery education initiative commenced in 2012, funded by the
Australian Government and led by the National Department of Health. One specific
objective of the initiative was to improve the standard of clinical teaching and
practice in four schools of midwifery. There were 394 midwives educated over the
4 year period (2012-2015) representing half of all midwives in Papua New Guinea.
A study was undertaken to describe the educational programme, employment,
practices and experiences of graduates who studied midwifery in 2012 and 2013 as
part of the initiative. OBJECTIVE: the aim of this paper is to explore the
education, employment and practice of newly graduated midwives in Papua New
Guinea. DESIGN: a mixed methods descriptive study design was used. Surveys and
focus groups were used to gather data. Ethical approval was granted by the
relevant Human Research Ethics Committees. SETTING AND PARTICIPANTS: all
midwifery graduates in 2012 and 2013 from the four midwifery schools in Papua New
Guinea were included in the study and almost 80% were contacted. FINDINGS: nearly
90% of graduates were working as midwives, with an additional 3% working as
midwifery or nursing educators. This study discovered that graduates exhibited
increased skills acquisition and confidence, leadership in maternal and newborn
care services and a marked improvement in the provision of respectful care to
women. The graduates faced challenges to implement evidence based care with
barriers including the lack of appropriate resources and differences of opinion
with senior staff. CONCLUSIONS: factors affecting the quality of midwifery
education will need to be addressed if Papua New Guinea is to continue to improve
the status of maternal and newborn health. Specifically, the length of the
midwifery education, the quality of clinical practice and the exposure to rural
and remote area practice need addressing in many contexts like Papua New Guinea.
PMID- 27498186
TI - How optimal caseload midwifery can modify predictors for preterm birth in young
women: Integrated findings from a mixed methods study.
AB - OBJECTIVE: to identify possible mechanisms by which caseload midwifery reduces
preterm birth for young childbearing women. DESIGN: a mixed methods
triangulation, convergence design was used to answer the research question 'How
does the way maternity care is provided affect the health and well-being of young
women and their babies?' The project generated quantitative and qualitative
findings which were collected and analysed concurrently then separately analysed
and published. The research design enabled integration of the quantitative and
qualitative findings for further interpretation through a critical pragmatic
lens. SETTING: a tertiary maternity hospital in Australia providing care to
approximately 500 pregnant young women (aged 21 years or less) each year. Three
distinct models of care were offered: caseload midwifery, young women's clinic,
and standard 'fragmented' care. PARTICIPANTS: a cohort study included data from
1971 young women and babies during 2008-2012. An ethnographic study included
analysis of focus group interviews with four caseload midwives in the young
women's midwifery group practice; as well as ten pregnant and postnatal young
women receiving caseload midwifery care. FINDINGS: integrated analysis of the
quantitative and qualitative findings suggested particular features in the model
of care which facilitated young women turning up for antenatal care (at an
earlier gestation and more frequently) and buying in to the process (disclosing
risks, engaging in self-care activities and accepting referrals for assistance).
We conceptualised that Optimal Caseload Midwifery promotes Synergistic Health
Engagement between midwife and the young woman. KEY CONCLUSIONS: optimal Caseload
Midwifery (which includes midwives with specific personal attributes and
philosophical commitments, along with appropriate institutional infrastructure
and support) facilitates midwives and young clients to develop trusting
relationships and engage in maternity care. Health engagement can modify
predictors for preterm birth that are common amongst pregnant adolescents by
promoting earlier maternity booking, sufficient antenatal care, greater emotional
resilience, ideal gestational weight gain, less smoking/drug use, and fewer
untreated genito-urinary infections. IMPLICATIONS FOR PRACTICE: the institutional
infrastructure and managerial support for caseload midwifery should value and
prioritise the philosophical commitments and personal attributes required to
optimise the model. Furthermore the location of visits, between appointment
access to primary midwife, and back-up system should be organised to optimise the
midwife-woman relationship in order to promote the young woman's engagement with
maternity care.
PMID- 27498187
TI - Poly(phosphorhydrazone) dendrimers: yin and yang of monocyte activation for human
NK cell amplification applied to immunotherapy against multiple myeloma.
AB - Human natural killer (NK) cells play a key role in anti-cancer and anti-viral
immunity, but their selective amplification in vitro is extremely tedious to
achieve and remains one of the most challenging problems to solve for efficient
NK cell-based immuno-therapeutic treatments against malignant diseases. Here we
report that, when added to ex vivo culture of peripheral blood mononuclear cells
from healthy volunteers or from cancer patients with multiple myeloma, poly
(phosphorhydrazone) dendrimers capped with amino-bis(methylene phosphonate) end
groups enable the efficient proliferation of NK cells with anti-cancer
cytotoxicity in vivo. We also show that the amplification of the NK population
relies on the preliminary activation of monocytes in the framework of a multistep
cross-talk between monocytes and NK cells before the proliferation thereof. Thus
poly(phosphorhydrazone) dendrimers represent a novel class of extremely promising
drugs to develop NK-cell based anti-cancer therapies.
PMID- 27498189
TI - Recent advances in the structural biology of the 26S proteasome.
AB - There is growing appreciation for the fundamental role of structural dynamics in
the function of macromolecules. In particular, the 26S proteasome, responsible
for selective protein degradation in an ATP dependent manner, exhibits dynamic
conformational changes that enable substrate processing. Recent cryo-electron
microscopy (cryo-EM) work has revealed the conformational dynamics of the 26S
proteasome and established the function of the different conformational states.
Technological advances such as direct electron detectors and image processing
algorithms allowed resolving the structure of the proteasome at atomic
resolution. Here we will review those studies and discuss their contribution to
our understanding of proteasome function.
PMID- 27498188
TI - Common Molecular Pathways in Amyotrophic Lateral Sclerosis and Frontotemporal
Dementia.
AB - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age
related neurodegenerative diseases in which predominantly motor neurons and
cerebral cortex neurons, respectively, are affected. Several novel ALS and FTD
disease genes have been recently discovered, pointing toward a few overarching
pathways in ALS/FTD pathogenesis. Nevertheless, a precise picture of how various
cellular processes cause neuronal death, or how different routes leading to ALS
and FTD are functionally connected is just emerging. Moreover, how the most
recent milestone findings in the ALS/FTD field might lead to improved diagnosis
and treatment is actively being explored. We highlight some of the most exciting
recent topics in the field, which could potentially facilitate the identification
of further links between the pathogenic ALS/FTD pathways related to autophagy,
vesicle trafficking, and RNA metabolism.
PMID- 27498190
TI - Phosphatidylinositol-3-phosphate regulates response of cells to proteotoxic
stress.
AB - Human Nedd4 ubiquitin ligase, or its variants, inhibit yeast cell growth by
disturbing the actin cytoskeleton organization and dynamics, and lead to an
increase in levels of ubiquitinated proteins. In a screen for multicopy
suppressors which rescue growth of yeast cells producing Nedd4 ligase with an
inactive WW4 domain (Nedd4w4), we identified a fragment of ATG2 gene encoding
part of the Atg2 core autophagy protein. Expression of the Atg2-C1 fragment (aa
1074-1447) improved growth, actin cytoskeleton organization, but did not
significantly change the levels of ubiquitinated proteins in these cells. The GFP
Atg2-C1 protein in Nedd4w4-producing cells primarily localized to a single
defined structure adjacent to the vacuole, surrounded by an actin filament ring,
containing Hsp42 and Hsp104 chaperones. This localization was not affected in
several atg deletion mutants, suggesting that it might be distinct from the
phagophore assembly site (PAS). However, deletion of ATG18 encoding a
phosphatidylinositol-3-phosphate (PI3P)-binding protein affected the morphology
of the GFP-Atg2-C1 structure while deletion of ATG14 encoding a subunit of PI3
kinase suppressed toxicity of Nedd4w4 independently of GFP-Atg2-C1. Further
analysis of the Atg2-C1 revealed that it contains an APT1 domain of previously
uncharacterized function. Most importantly, we showed that this domain is able to
bind phosphatidylinositol phosphates, especially PI3P, which is abundant in the
PAS and endosomes. Together our results suggest that human Nedd4 ubiquitinates
proteins in yeast and causes proteotoxic stress and, with some Atg proteins,
leads to formation of a perivacuolar structure, which may be involved in
sequestration, aggregation or degradation of proteins.
PMID- 27498191
TI - SOX9 regulates expression of the male fertility gene Ets variant factor 5 (ETV5)
during mammalian sex development.
AB - In humans, dysregulation of the sex determining gene SRY-box 9 (SOX9) leads to
disorders of sex development (DSD). In mice, knock-out of Sox9 prior to sex
determination leads to XY sex reversal, while Sox9 inactivation after sex
determination leads to spermatogenesis defects. SOX9 specifies the
differentiation and function of Sertoli cells from somatic cell precursors, which
then orchestrate the development and maintenance of other testicular cell types,
largely through unknown mechanisms. Here, we describe a novel testicular target
gene of SOX9, Ets variant factor 5 (ETV5), a transcription factor responsible for
maintaining the spermatogonial stem cell niche. Etv5 was highly expressed in wild
type XY but not XX mouse fetal gonads, with ETV5 protein localized in the Sertoli
cells, interstitial cells and germ cells of the testis. In XY Sox9 knock-out
gonads, Etv5 expression was strongly down-regulated. Similarly, knock-down of
SOX9 in the human Sertoli-like cell line NT2/D1 caused a decrease in ETV5 gene
expression. Transcriptomic analysis of NT2/D1 cells over-expressing SOX9 showed
that ETV5 expression was increased in response to SOX9. Moreover, chromatin
immunoprecipitation of these cells, as well as of embryonic mouse gonads, showed
direct binding of SOX9 to ETV5 regulatory regions. We demonstrate that SOX9 was
able to activate ETV5 expression via a conserved SOX site in the 5' regulatory
region, mutation of which led to loss of activation. In conclusion, we present a
novel target gene of SOX9 in the testis, and suggest that SOX9 regulation of ETV5
contributes to the control of male fertility.
PMID- 27498192
TI - Single and repeated exposures to the volatile anesthetic isoflurane do not impair
operant performance in aged rats.
AB - Postoperative Cognitive Dysfunction (POCD) is a complication that can occur in
the elderly after anesthesia and surgery and is characterized by impairments in
information processing, memory, and executive function. Currently, it is unclear
whether POCD is due to the effects of surgery, anesthesia, or perhaps some
interaction between these or other perioperative variables. Studies in rodents
suggest that the development of POCD may be related directly to anesthesia
induced neuroactivity. Volatile anesthetics have been shown to increase cellular
inflammation and apoptosis within the hippocampus of aged rodents, while
producing corresponding impairments in hippocampal-dependent brain functions.
However, it is unclear whether volatile anesthetics can affect additional aspects
of cognition that do not primarily depend upon the hippocampus. The purpose of
this study was to use established operant tests to examine the effects of
isoflurane on aspects of behavioral inhibition, learning, and motivation in aged
rats. Twenty-one adult Sprague-Dawley rats (11 male, 10 female) were trained to
perform fixed consecutive number (FCN), incremental repeated acquisition (IRA),
and progressive ratio (PR) tasks for a minimum of 15 months prior to receiving
anesthesia. At 23 months of age, rats were exposed to 1.3% isoflurane or medical
grade air for 2h. Initial results revealed that a 2h exposure to isoflurane had
no effect on IRA, FCN, or PR performance. Thus, rats received 3 additional
exposures to 1.3% isoflurane or medical grade air: 2, 4 and 6h exposures with 2
weeks elapsing before exposure two, 3 weeks elapsing between exposures two and
three, and 2 weeks elapsing between exposures three and four. These additional
exposures had no observable effects on performance of any operant task. These
results suggest that single and repeated exposures to isoflurane do not impair
the performance of aged rats in tasks designed to measure behavioral inhibition,
learning, and motivation. This lack of significant effect suggests that the
impairments associated with isoflurane exposure may not generalize to all aspects
of cognition, but may be selective to tasks that primarily measure spatial memory
processes.
PMID- 27498193
TI - Characterization of Roseomonas and Nocardioides spp. for arsenic transformation.
AB - The metalloid arsenic predominantly exists in the arsenite [As(III)] and arsenate
[As(V)]. These two forms are respectively oxidized and reduced by microbial redox
processes. This study was designed to bioprospect arsenic tolerating bacteria
from Lonar lake and to characterize their arsenic redoxing ability. Screening of
sixty-nine bacterial species isolated from Lonar lake led to identification of
three arsenic-oxidizing and seven arsenic-reducing species. Arsenite oxidizing
isolate Roseomonas sp. L-159a being closely related to Roseomonas cervicalis ATCC
49957 oxidized 2mM As(III) in 60h. Gene expression of large and small subunits of
arsenite oxidase respectively showed 15- and 17-fold higher expression. Another
isolate Nocardioides sp. L-37a formed a clade with Nocardioides ghangwensis
JC2055, exhibited normal growth with different carbon sources and pH ranges. It
reduced 2mM As(V) in 36h and showed constitutive expression of arsenate reductase
which increased over 4-fold upon As(V) exposure. Genetic markers related to
arsenic transformation were identified and characterized from the two isolates.
Moderate resistance against the arsenicals was exhibited by the two isolates in
the range of 1-5mM for As(III) and 1-200mM for As(V). Altogether we provide
multiple evidences to indicate that Roseomonas sp. and Nocardioides sp. exhibited
arsenic transformation ability.
PMID- 27498194
TI - Malignant Myoepithelioma of the Breast Clinically and Histologically Masquerading
as Angiosarcoma: Cytological Findings and Review of the Literature.
AB - BACKGROUND: Malignant myoepithelioma of the breast is an exceptionally rare,
aggressive tumor with a diverse morphology, the cytological features of which
have only occasionally been described. CASE REPORT: Our case comprises a 74-year
old woman who was admitted to our hospital with an erythematous, inflammatory
like mass of her left breast with nipple ulceration, and clinically fixed to the
chest wall. The woman underwent fine-needle aspiration and biopsy. The aspirates
consisted mainly of loose aggregates of large, highly pleomorphic, polygonal
epithelioid cells as well as aggregates of spindle cells with prominent, easily
detectable mitoses and single, multinucleated pleomorphic giant cells. The
cytological diagnosis was consistent with high-grade malignancy. Histologically,
the lesion consisted broadly of eosinophilic epithelioid cells with globoid
cytoplasm in a reticulated, angiomatoid pattern and of spindle (sarcomatoid)
cells in a storiform pattern, highly suspicious of angiosarcoma. A final
diagnosis of malignant myoepithelioma was made. CONCLUSION: We present the
cytological findings in comparison with the unusual histological features of a
malignant myoepithelioma of the breast. A high degree of suspicion with a keen
eye for morphological details coupled with relevant immunohistochemistry will aid
in arriving at the correct diagnosis.
PMID- 27498195
TI - Lipocalin-2 as a therapeutic target for brain injury: An astrocentric
perspective.
AB - Lipocalin-2 (LCN2) is a member of the secreted lipocalin protein family. LCN2 is
also a representative gliocalin that is primarily released by glial cells, as
well as acts upon them. Astrocytes are one of the major cellular sources of LCN2
under brain injury conditions. Astrocytes secrete LCN2 to promote
neuroinflammation. Studies using Lcn2 knockout animals and cultured neural cells
suggest an important role of LCN2 in regulating the development of hemorrhagic
and ischemic stroke as well as other brain injuries. The clinical relevance of
LCN2 is supported by studies on patients with stroke. Mechanistic studies have
revealed that LCN2 is a molecular switch for determining the phenotypic fate of
astrocytes under inflammatory conditions. LCN2 gene expression is regulated at
the multiple levels; mostly at the transcription level, post-transcription level
by microRNAs, and protein level by minor post-translational modification. Recent
advances in LCN2 research strongly indicate that astrocytic LCN2 is a promising
drug target for the injured brain. Future research should focus on its
translational aspects, such as developing small-molecule inhibitors or
neutralizing antibodies to target LCN2 for the treatment of brain injury.
However, spatiotemporally complex roles of LCN2, which are either beneficial or
deleterious, should be considered when targeting LCN2. The potential use of LCN2
as a biomarker for the diagnosis and prognosis of various brain disorders is also
discussed.
PMID- 27498196
TI - Ciprofloxacin provokes SOS-dependent changes in respiration and membrane
potential and causes alterations in the redox status of Escherichia coli.
AB - An in-depth understanding of the physiological response of bacteria to antibiotic
induced stress is needed for development of new approaches to combatting
microbial infections. Fluoroquinolone ciprofloxacin causes phase alterations in
Escherichia coli respiration and membrane potential that strongly depend on its
concentration. Concentrations lower than the optimal bactericidal concentration
(OBC) do not inhibit respiration during the first phase. A dose higher than the
OBC provokes immediate SOS-independent inhibition of respiration and growth that
can contribute to a decreased SOS response and lowered susceptibility to high
concentrations of ciprofloxacin. Cells retain their metabolic activity, membrane
potential and accelerated K+ uptake and produce low levels of superoxide and H2O2
during the first phase. The time before initiation of the second phase is
inversely correlated with the ciprofloxacin concentration. The second phase is
SOS-dependent and characterized by respiratory inhibition, membrane
depolarization, K+ and glutathione leakage and cessation of glucose consumption
and may be considered as cell death. atpA, gshA and kefBkefC knockouts, which
perturb fluxes of protons and K+, can modify the degree and duration of
respiratory inhibition and potassium retention. Loss of K+ efflux channels KefB
and KefC enhances the susceptibility of E. coli to ciprofloxacin.
PMID- 27498197
TI - Incidence, Risk Factors and a Novel Prevention Technique for Inguinal Hernia
after Robot-Assisted Radical Prostatectomy.
AB - INTRODUCTION: To evaluate the incidence and risk factors for postoperative
inguinal hernia (IH) after robot-assisted radical prostatectomy (RARP) and to
assess whether a newly developed prevention technique reduces the incidence of IH
after RARP. METHODS: We included 161 consecutive patients (322 groins) who
underwent RARP between September 2011 and October 2013. The prevention technique
was as follows: (1) sufficient incision of peritoneum around the internal
inguinal ring; (2) separation of spermatic vessels; (3) dissection of vas
deferens. RESULTS: Postoperative IH occurred in 14 cases (19.4%) occurring in the
observation group compared to 2 cases (2.2%) in the prevention group. Patent
processus vaginalis (PPV) was the only risk factor. Time-to-event analysis
demonstrated a significant decrease in IH incidence in the IH prevention group (p
= 0.005). CONCLUSION: Our data reveal a higher incidence of IH after RARP, with
the existence of PPV as the only identified risk factor. Our simple IH-prevention
technique, which does not involve the use of artificial materials, appears safe
and effective.
PMID- 27498198
TI - HIV Testing Among Internet-Using MSM in the United States: Systematic Review.
AB - Regular HIV testing enables early identification and treatment of HIV among at
risk men who have sex with men (MSM). Characterizing HIV testing needs for
Internet-using MSM informs development of Internet-facilitated testing
interventions. In this systematic review we analyze HIV testing patterns among
Internet-using MSM in the United States who report, through participation in an
online study or survey, their HIV status as negative or unknown and identify
demographic or behavioral risk factors associated with testing. We systematically
searched multiple electronic databases for relevant English-language articles
published between January 1, 2005 and December 16, 2014. Using meta-analysis, we
summarized the proportion of Internet-using MSM who had ever tested for HIV and
the proportion who tested in the 12 months preceding participation in the online
study or survey. We also identified factors predictive of these outcomes using
meta-regression and narrative synthesis. Thirty-two studies that enrolled 83,186
MSM met our inclusion criteria. Among the studies reporting data for each
outcome, 85 % (95 % CI 82-87 %) of participants had ever tested, and 58 % (95 %
CI 53-63 %) had tested in the year preceding enrollment in the study, among those
for whom those data were reported. Age over 30 years, at least a college
education, use of drugs, and self-identification as being homosexual or gay were
associated with ever having tested for HIV. A large majority of Internet-using
MSM indicated they had been tested for HIV at some point in the past. A smaller
proportion-but still a majority-reported they had been tested within the year
preceding study or survey participation. MSM who self-identify as heterosexual or
bisexual, are younger, or who use drugs (including non-injection drugs) may be
less likely to have ever tested for HIV. The overall findings of our systematic
review are encouraging; however, a subpopulation of MSM may benefit from targeted
outreach. These findings indicate unmet needs for HIV testing among Internet
using MSM and identify subpopulations that might benefit from targeted outreach,
such as provision of HIV self-testing kits.
PMID- 27498199
TI - Opicapone: A Review in Parkinson's Disease.
AB - Oral opicapone (Ongentys((r))), a potent, third-generation, long-acting,
peripheral catechol-O-methyltransferase (COMT) inhibitor, is approved as
adjunctive treatment to levodopa (L-Dopa)/dopa-decarboxylase inhibitor (DDCI)
therapy in adults with Parkinson's disease (PD) and end-of-dose motor
fluctuations who cannot be stabilized on those combinations. In 14- to 15-week,
double-blind, multinational trials and in 1-year, open-label extension studies in
this patient population, opicapone was an effective and generally well tolerated
adjunctive therapy to L-Dopa plus a DDCI and other PD therapy. During the double
blind phase, adjunctive opicapone 50 mg once daily provided significantly greater
improvements in motor fluctuations than placebo, with these improvements
noninferior to those with entacapone. These beneficial improvements in motor
fluctuations with opicapone were maintained in patients who continued adjunctive
opicapone during the extension studies, with patients who switched from placebo
or entacapone to opicapone experiencing significant improvements in motor
fluctuations during this year. No new unexpected safety concerns were identified
after ~1.4 years' treatment with opicapone, with no serious cases of
hepatotoxicity reported in clinical trials. With its convenient once-daily
regimen, oral opicapone is an emerging COMT inhibitor option for use as
adjunctive therapy to L-Dopa/DDCI therapy in adults with PD and end-of dose motor
fluctuations who cannot be stabilized on those combinations.
PMID- 27498200
TI - Regulation and the Mechanism of Estrogen on Cav1.2 Gene in Rat-Cultured Cortical
Astrocytes.
AB - L-type calcium channel (LTCC) gene Cav1.2 is believed to play an important role
in the alteration of Ca(2+) homeostasis in brain astrocytes. Increasing evidence
shows that alteration of intracellular Ca(2+) concentration is related to the
effect of 17beta-estradiol (E2) in a variety of neurophysiological and
neuropathological conditions. In this study, we measured immunoreactivity of
Cav1.2 protein expression in rat primary cortical astrocytes by using Western
blots. We demonstrated that E2 upregulated Cav1.2 expression in a dose- and time
dependent manner and the effect of E2 on Cav1.2 expression were blocked by an
estrogen receptor (ER) antagonist, ICI-182,780. The ER subtype-selective ERalpha
agonists propylpyrazole triole (PPT) and ERbeta agonist diarylpropionitrile (DPN)
both increase the expression of Cav1.2 in a dose-dependent manner. Also, the PPT
most closely mimicked the upregulation of Cav1.2 protein expression by E2.
Similar experiments of 10 nM E2-treated ERalpha- or ERbeta-knockdown astrocytes
have also shown that the E2 regulation of Cav1.2 protein expression is mediated
through an ERalpha-dependent pathway. Furthermore, we established that E2 did not
change the level of Cav1.2 mRNA. The induction of E2-mediated Cav1.2 expression
was inhibited by cycloheximide (CHX) but not by actinomycin D (Act-D), suggesting
that E2 regulation of Cav1.2 expression occurred at a posttranscriptional level.
We also found that E2 may increase Cav1.2 levels by decreasing its ubiquitination
and degradation rate. These findings provide new information about the effect of
E2 on Cav1.2 in astrocytes, particularly necessary for the treatment of
neurological disease.
PMID- 27498202
TI - Management of locoregional recurrence in cutaneous squamous cell carcinoma of the
head and neck.
AB - Cutaneous squamous cell carcinomas often affect elderly patients. Follow-up
monitoring is difficult in these patients due to their multi-morbidity and
reduced compliance. Tumour recurrence is consequently diagnosed in advanced
tumour stages. Surgical therapy with curative intention often requires extended
resections. The study at hand should determine whether surgical concepts are
warranted in this collective. Sixty-seven patients who underwent surgical
procedure due to recurrent disease of cutaneous head and neck squamous cell
carcinoma were included. The cohort was divided in patients with/without adjuvant
therapeutic regimens. Data were assessed retrospectively. Complete tumour
resection was achieved in 85 % of our patients. Patients with adjuvant treatment
demonstrated a favorable 5-year-recurrence-free interval (78 vs 30 %) and overall
survival (79 vs 46 %). Complete surgical resection of advanced recurrent head and
neck cutaneous squamous cell carcinomas is possible and yields favorable results
in terms of survival, especially if combined with adjuvant treatment.
PMID- 27498201
TI - The Neurobiology and Age-Related Prevalence of the epsilon4 Allele of
Apolipoprotein E in Alzheimer's Disease Cohorts.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised
by amyloid beta (Abeta) plaques and tau neurofibrillary tangles in the brain.
Human apolipoprotein E (ApoE) is a lipid transport protein coded by the
polymorphic APOE gene, with three major alleles: epsilon2, epsilon3 and epsilon4.
After age, the epsilon4 allele is the greatest risk factor for developing
sporadic AD, conferring an increased risk of 3-4 and 8-12 times for one or two
copies of the allele, respectively. This risk is reported to vary by demographic
factors including sex, ethnicity and geography. In order to understand the risk
of ApoE epsilon4 in relation to age, the primary risk factor for developing AD,
we need to understand how the prevalence of APOE genotypes changes with age.
Here, we present the first data on age-related prevalence of APOE epsilon4 in AD
in three AD cohorts in Australia and the USA. There is a significant association
between age and epsilon4 prevalence, particularly for epsilon4 homozygotes, such
that as age increases the prevalence of epsilon4 decreases. Further studies on a
random, population-based sample of the population are needed to provide more
generalizable data, particularly in the >90-year-old age group.
PMID- 27498204
TI - Toward a theory of organisms: Three founding principles in search of a useful
integration.
AB - Organisms, be they uni- or multi-cellular, are agents capable of creating their
own norms; they are continuously harmonizing their ability to create novelty and
stability, that is, they combine plasticity with robustness. Here we articulate
the three principles for a theory of organisms, namely: the default state of
proliferation with variation and motility, the principle of variation and the
principle of organization. These principles profoundly change both biological
observables and their determination with respect to the theoretical framework of
physical theories. This radical change opens up the possibility of anchoring
mathematical modeling in biologically proper principles.
PMID- 27498203
TI - Pretreatment factors associated with functional oral intake and feeding tube use
at 1 and 6 months post-radiotherapy (+/- chemotherapy) for head and neck cancer.
AB - A proportion of patients with head and neck cancer (HNC) experience significant
swallowing difficulty during and post-radiotherapy/chemoradiotherapy (RT/CRT).
Identifying patients during the pretreatment period who are anticipated to have
compromised oral intake would allow for early and accurate patient education, and
prioritisation of their management. Ascertaining a clear set of pretreatment
predictors from the literature is challenging due to heterogeneity in study
designs and patient cohorts, with minimal prospective data available (especially
at 1-month post-treatment). The objectives of this study were to investigate
which pretreatment factors predicted compromised oral intake and feeding tube use
at 1 and 6 months post-RT/CRT. Prospective data were collected on 80 consecutive
HNC patients receiving RT/CRT from 2011 to 2014. The primary outcome was to
identify predictors of a modified diet at 1 and 6 months post-RT/CRT. Secondary
outcomes were to identify predictors of feeding tube use at these time intervals,
and <6 vs. >6 week duration of feeding tube use. Multivariate analysis revealed
bilateral neck radiotherapy treatment was a strong predictor of modified diets at
1 month (p < 0.001), and T-stages T3/T4 a predictor of modified diets at 6 months
(p = 0.03). Patients treated with concurrent CRT (p = 0.02) and bilateral neck
treatment (p = 0.02) predicted feeding tube use at 1 month, and concurrent CRT
predicted feeding tube use for >6 weeks (p = 0.04). Therefore, patients receiving
bilateral neck treatment and/or CRT are at greatest risk of requiring modified
diets and feeding tube use early post-treatment, and should be prioritised for
intervention and ongoing support.
PMID- 27498205
TI - Applying Data Mining Techniques to Improve Breast Cancer Diagnosis.
AB - In the field of breast cancer research, and more than ever, new computer aided
diagnosis based systems have been developed aiming to reduce diagnostic tests
false-positives. Within this work, we present a data mining based approach which
might support oncologists in the process of breast cancer classification and
diagnosis. The present study aims to compare two breast cancer datasets and find
the best methods in predicting benign/malignant lesions, breast density
classification, and even for finding identification (mass / microcalcification
distinction). To carry out these tasks, two matrices of texture features
extraction were implemented using Matlab, and classified using data mining
algorithms, on WEKA. Results revealed good percentages of accuracy for each
class: 89.3 to 64.7 % - benign/malignant; 75.8 to 78.3 % - dense/fatty tissue;
71.0 to 83.1 % - finding identification. Among the different tests classifiers,
Naive Bayes was the best to identify masses texture, and Random Forests was the
first or second best classifier for the majority of tested groups.
PMID- 27498206
TI - Plasmapheresis for the treatment of kidney diseases.
AB - The purpose of this review is to examine the evidence supporting the application
of plasma exchange in renal disease. Our review focuses on the following 6 most
common renal indications for plasma exchange based on 2014 registry data from the
Canadian Apheresis Group: (i) thrombotic thrombocytopenic purpura (TTP)/hemolytic
uremic syndrome; (ii) renal transplantation, (iii) anti-neutrophil cytoplasm
antibodies-associated vasculitis, (iv) cryoglobulinemia, (v) focal segmental
glomerulosclerosis, and (vi) Goodpasture syndrome. The rarity of these diseases
and their rapid, often fatal course mean that randomized controlled studies of
plasma exchange are rarely conducted. Although evidence from an adequately
powered randomized controlled trial supports the use of plasma exchange to treat
thrombotic thrombocytopenic purpura, the use of plasma exchange to treat other
renal diseases is only supported by observational and mechanistic studies. Larger
well-designed trials are needed to clarify the potential role of plasma exchange
in renal disease. Growing international collaboration will improve the quality of
future studies in this area.
PMID- 27498207
TI - Neural Correlates of the Antinociceptive Effects of Stimulating the Anterior
Pretectal Nucleus in Rats.
AB - : Stimulation-evoked antinociception (SEA) from the anterior pretectal nucleus
(APtN) activates mechanisms that descend to the spinal cord through the
dorsolateral funiculus, but the encephalic route followed by the descending
pathways from the APtN is not completely known. This study evaluated the changes
in the SEA from the APtN in the Wistar rat tail-flick test after lidocaine
induced neural block or N-methyl-d-aspartate-induced neurotoxic lesion of the
deep mesencephalic nucleus (DpMe), tegmental pedunculopontine nucleus (PPTg), or
lateral paragigantocellular nucleus (LPGi). The SEA from the APtN was less
intense after neural block of the contralateral DpMe or PPTg or the ipsilateral
LPGi, but was not changed by the neural block of the ipsilateral DpMe or PPTg or
the contralateral LPGi. Antinociception did not occur when APtN stimulation was
carried out 5 minutes after lidocaine or 6 days after N-methyl-d-aspartate
injections into the contralateral DpMe and the ipsilateral LPGi, or into the
contralateral PPTg and the ipsilateral LPGi. We conclude that the SEA from the
APtN activates 2 descending pain inhibitory pathways, one relaying in the
ipsilateral LPGi and another relaying sequentially in the contralateral DpMe and
PPTg. PERSPECTIVE: The antinociceptive effect of the APtN stimulation involves 2
descending pathways: one relaying in the ipsilateral LPGi and another descending
contralaterally via relays in the DpMe and PPTg.
PMID- 27498208
TI - The potential implication of SCN1A and CYP3A5 genetic variants on antiepileptic
drug resistance among Egyptian epileptic children.
AB - PURPOSE: Despite the advances in the pharmacological treatment of epilepsy,
pharmacoresistance still remains challenging. Understanding of the
pharmacogenetic causes is critical to predict drug response hence providing a
basis for personalized medications. Genetic alteration in activity of drug target
and drug metabolizing proteins could explain the development of pharmacoresistant
epilepsy. So the aim of this study was to explore whether SCN1A c.3184 A/G
(rs2298771) and CYP3A5*3 (rs776746) polymorphisms could serve as genetic based
biomarkers to predict pharmacoresistance among Egyptian epileptic children.
METHODS: Genotyping of SCN1A c.3184 A/G and CYP3A5*3 polymorphisms using the
polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
method was performed in 65 healthy control subjects and 130 patients with
epilepsy, of whom 50 were drug resistant and 80 were drug responsive. RESULTS:
There was a significant higher frequency of the AG genotype (p=0.001) and G
allele (p=0.006) of SCN1A polymorphism in epileptic patients than in controls.
Also their frequency was significantly higher in drug resistant patients in
comparison with drug responders (p=0.005 and 0.054 respectively). No significant
association between CYP3A5*3 polymorphism and drug-resistance was found.
CONCLUSIONS: Overall, results confirmed the claimed role of SCN1A c.3184 A/G
polymorphism in epilepsy and moreover in development of pharmacoresistance among
Egyptian epileptic children. CYP3A5*3 variants have no contributing effect on
pharmacoresistance among Egyptian epileptic children.
PMID- 27498209
TI - Physical Therapy in the Treatment of Central Pain Mechanisms for Female Sexual
Pain.
AB - INTRODUCTION: The complexity of female sexual pain requires an interdisciplinary
approach. Physical therapists trained in pelvic health conditions are well
positioned to be active members of an interdisciplinary team addressing the
assessment and treatment of female sexual pain. Changes within physical therapy
practice in the last ten years have resulted in significant utilization of pelvic
floor muscle relaxation and manual therapy techniques to address a variety of
pelvic pain conditions, including female sexual pain. However, sexual pain is a
complex issue giving credence to the necessity of addressing all of the drivers
of the pain experience- biological, psychological and social. AIM: This review
aims to reconcile current pain science with a plan for integrating a
biopsychosocial approach into the evaluation and subsequent treatment for female
sexual pain for physical therapists. METHODS: A literature review of the
important components of skilled physical therapy interventions is presented
including the physical examination, pain biology education, cognitive behavioral
influences in treatment design, motivational interviewing as an adjunct to
empathetic practice, and the integration of non-threatening movement and
mindfulness into treatment. MAIN OUTCOME MEASURE: A single case study is used to
demonstrate the biopsychosocial framework utilized in this approach. RESULTS:
Appropriate measures for assessing psychosocial factors are readily available and
inform a reasoned approach for physical therapy design that addresses both
peripheral and central pain mechanisms. Decades of research support the
integration of a biopsychosocial approach in the treatment of complex pain,
including female sexual pain. CONCLUSION: It is reasonable for physical
therapists to utilize evidence based strategies such as CBT, pain biology
education, Mindfulness Based Stress Reduction (MBSR), yoga and imagery based
exercises to address the biopsychosocial components of female sexual pain.
PMID- 27498210
TI - The impact of outpatient systemic anti-cancer treatment on patient costs and work
practices.
AB - BACKGROUND: There is extensive focus on the rising costs of healthcare. However,
for patients undergoing cancer treatment, there are additional personal costs,
which are poorly characterised. AIM: To qualify indirect costs during anti-cancer
therapy in a designated Irish cancer centre. METHODS: An anonymous questionnaire
collected demographic data, current work practice, and personal expenditure on
regular and non-regular indirect costs during treatment. Differences between
groups of interest were compared using the Mann-Whitney U test. RESULTS: In
total, there were 151 responders of median age 58 years; 60 % were female and 74
% were not working. Breast cancer (29 %) was the most frequent diagnosis.
Indirect costs totalled a median of ?1138 (range ?21.60-?7089.84) per patient,
with median monthly outgoings of ?354. The greatest median monthly costs were
hair accessories (?400), transportation (?65), and complementary therapies (?55).
The majority (74 %) of patients used a car and median monthly fuel expenditure
was ?31 (range ?1.44-?463.32). Women spent more money during treatment (?1617)
than men (?974, p = 0.00128). In addition, median monthly expenditure was greater
for those less than 50 years old (?1621 vs ?1105; p = 0.04236), those who lived
greater than 25 km away (?2015 vs ?1078; p = 0.00008) and those without a medical
card (?2023 vs ?961; p = 0.00024). CONCLUSION: This study highlights the need for
greater awareness of indirect expenditures associated with systemic anti-cancer
therapy in Ireland.
PMID- 27498211
TI - A systematic review of serious video games used for vaccination.
AB - INTRODUCTION: Vaccination is an effective and proven method of preventing
infectious diseases. However, uptake has not been optimal with available vaccines
partly due to vaccination hesitancy. Various public health approaches have
adressed vaccination hesitancy. Serious video games involving vaccination may
represent an innovative public health approach. The aim of this study was to
identify, describe, and review existing serious video games on vaccination.
METHOD: A systematic review was performed. Various databases were used to find
data on vaccination-related serious video games published from January 1st 2000
to May 15th 2015. Data including featured medical and vaccination content,
publication characteristics and games classification were collected for each
identified serious game. RESULTS: Sixteen serious video games involved in
vaccination were identified. All games were developed in high-income countries
between 2003 and 2014. The majority of games were available online and were
sponsored by educational/health institutions. All games were free of charge to
users. Edugame was the most prevalent serious game subcategory. Twelve games were
infectious disease-specific and the majority concerned influenza. The main
objective of the games was disease control with a collective perspective.
Utilization data was available for two games. Two games were formally evaluated.
DISCUSSION: The use of serious video games for vaccination is an innovative tool
for public health. Evaluation of vaccination related serious video games should
be encouraged to demonstrate their efficacy and utility.
PMID- 27498212
TI - A decade of adaptation: Regulatory contributions of the World Health Organization
to the Global Action Plan for Influenza Vaccines (2006-2016).
AB - The Global Action Plan (GAP) for Influenza Vaccines is a decade-long initiative
that brings together a diverse range of stakeholders to work towards reducing
anticipated global shortage of influenza vaccines and ensuring more equitable
access to vaccines during the next influenza pandemic. Since its inception in
2006, significant progress has been made towards all the main objectives of GAP,
namely: (1) an increase in seasonal vaccine use, (2) an increase in vaccine
production, and (3) progress in research and development of more effective
vaccines. The Technology Transfer Initiative (TTI), conceived and managed by WHO
under the GAP, contributed to increasing regional influenza vaccine production
capacity. This was achieved by facilitating technology transfer in 14 low- and
middle-income countries, through grants to manufacturers to establish or
strengthen influenza vaccine production capacity and support to their national
regulatory authorities. Five of the countries subsequently licensed locally
produced influenza vaccines; two pandemic and three seasonal vaccines received
WHO prequalification. The success of GAP can be largely attributed to the
regulatory support provided by WHO to both manufacturers and regulators. This
support had two components: (1) direct regulatory support to GAP/TTI, and (2)
support to GAP-related WHO programmes, such as the Pandemic Influenza Vaccine
Deployment Initiative in 2010 and the Pandemic Influenza Preparedness Framework
since 2013, especially in non-vaccine-producing countries. Temporary adaptation
of the assessment process for influenza vaccines in the WHO Vaccine
Prequalification Programme to the A(H1N1) pandemic situation in 2009 was
instrumental to the success of the WHO Pandemic Influenza Vaccine Deployment
Initiative in its attempt to meet the demand for pandemic vaccines in countries
that received donated vaccines.
PMID- 27498213
TI - Enhancement of fibroblast activation protein alpha-based vaccines and adenovirus
boost immunity by cyclophosphamide through inhibiting IL-10 expression in 4T1
tumor bearing mice.
AB - Fibroblast activation protein alpha (FAPalpha) is expressed in cancer-associated
fibroblasts (CAFs) of more than 90% of malignant epithelia carcinomas. CAFs are
the main type of cells in the tumor microenvironment which offer nutrition and
protection to the tumor and regulate immunosuppression. To eliminate CAFs, a
vaccine targeting FAPalpha may be used with a heterologous prime-boost strategy
to enhance the FAPalpha-specific cellular immunity. Here, a FAP vaccine using a
recombinant adenovirus (rAd) vector was constructed as well as a DNA vaccine
reported in our previous work. Although the DNA prime-rAd boost strategy enhanced
FAPalpha-specific immune responses, improvement of anti-tumor immunity effects
was not observed. Examination of immunosuppressive factors revealed that high
expression of the IL-10 cytokine was considered the main cause of the failure of
the prime-boost strategy. However, heterologous vaccination in combination with a
low-dose of cyclophosphamide (CY), which was reported to reduce IL-10 production
and promote a shift from immunosuppression to immunopotentiation, resulted in
enhanced effects in terms of numbers of effector T cells and tumor growth
inhibition rates, compared to the CY alone or DNA alone group. Tumor growth was
inhibited markedly when the prime-boost strategy was combined with CY in both the
prophylactic and therapeutic settings and the survival time of 4T1 tumor bearing
mice was also prolonged significantly. With the reduction of IL-10, enhancement
of the anti-tumor effect by the prime-boost strategy was observed. These results
suggest that FAPalpha-targeted rAd boosting in combination with CY is an
attractive approach to overcoming immunosuppression in cancer vaccines.
PMID- 27498214
TI - Lubricin/proteoglycan 4 increases in both experimental and naturally occurring
equine osteoarthritis.
AB - OBJECTIVE: The goals of this study were (1) to quantify proteoglycan 4 (PRG4)
gene expression; (2) to assess lubricin immunostaining; and (3) to measure
synovial fluid lubricin concentrations in clinical and experimental models of
equine carpal osteoarthritis (OA). DESIGN: Lubricin synovial fluid concentrations
and cartilage and synovial membrane PRG4 expression were analyzed in research
horses undergoing experimental OA induction (n = 8) and in equine clinical
patients with carpal OA (n = 58). Lubricin concentrations were measured using a
custom sandwich enzyme-linked immunosorbent assay, and PRG4 expression was
quantified using qRT-PCR. Lubricin immunostaining was assessed in synovial
membrane and osteochondral sections in the experimental model. RESULTS: Lubricin
concentrations increased in synovial fluid following induction of OA, peaking at
21 days post-operatively in OA joints vs sham-operated controls (331 +/- 69
MUg/mL vs 110 +/- 19 MUg/mL, P = 0.001). Lubricin concentrations also increased
in horses with naturally occurring OA as compared to control joints (152 +/- 32
MUg/mL vs 68 +/- 4 MUg/mL, P = 0.003). Synovial membrane PRG4 expression
increased nearly 2-fold in naturally occurring OA (P = 0.003), whereas cartilage
PRG4 expression decreased 2.5-fold (P = 0.025). Lubricin immunostaining was more
pronounced in synovial membrane from OA joints as compared to controls, with
intense lubricin localization to sites of cartilage damage. CONCLUSIONS: Although
PRG4 gene expression decreases in OA cartilage, synovial membrane PRG4
expression, synovial fluid lubricin concentrations and lubricin immunostaining
all increase in an equine OA model. Lubricin may be elevated to protect joints
from post-traumatic OA.
PMID- 27498215
TI - Adiponectin, TNF-alpha and inflammatory cytokines and risk of type 2 diabetes: A
systematic review and meta-analysis.
AB - AIMS: There has been growing evidence that adiponectin, tumor necrosis factor
alpha (TNF-alpha) and inflammatory cytokines involved in insulin resistance and
may be attractive candidates for assessing risk of the incident type 2 diabetes
(T2DM). A systematic review and meta-analysis of prospective studies was
conducted to assess the associations of levels of serum adiponectin, TNF-alpha
and inflammatory markers (Interleukin-1 beta (IL-1beta), Interleukin-6 (IL-6),
Interleukin-18 (IL-18), C-reactive protein (CRP)) with risk of T2DM.
MATERIALS/METHODS: We searched PubMed, ISI Web of Knowledge, EMBASE, and Cochrane
Library databases up until February 1, 2016 for eligible studies which were
matched to search subjects. Either fixed-effects or random-effects models were
used to estimate the summary risk incorporated between study variations. RESULTS:
19 studies comprising a total of 39,136 participants and 7924 cases were included
in the meta-analysis. Our findings showed that an obvious association of elevated
CRP levels with T2DM risk (relative risk [RR] 1.48 [95% CI 1.26-1.71]), with the
absence of publication bias. For IL-6, the meta-analysis involved 16 cohorts with
a total of 24,929 participants and 4751 cases. Using data from all trials, a
strong positive correlation (1.32 [1.14, 1.51]) was observed between basal plasma
IL-6 and T2DM, whereas relatively lower relation between TNF-alpha (1.16 [0.87,
1.45]), IL-18 (1.45 [1.16, 1.73]), IL-1beta (0.87, [0.59, 1.15]) and
independently increased risk to occurrence of T2DM. Conversely, we also found
that the level of adiponectin decreased significantly in patients with T2DM.
Sensitivity analyses further supported the associations. CONCLUSIONS: This meta
analysis indicates that T2DM risk as whole was strongly associated with elevated
levels of inflammatory cytokines (IL-1beta, IL-6, IL-18, CRP), TNF-alpha and low
levels of adiponectin. Despite an overall detectable association in the meta
analysis, considerable heterogeneity existed between studies. Further work is
needed, it seems clear that a complex interplay of inflammation and the
development of DM. Moreover, these biomarkers are predictors of T2DM subjects and
should take more attention to measure levels of these as well as to target
therapy/interventions.
PMID- 27498216
TI - Cryopreservation of human spermatozoa with minimal non-permeable cryoprotectant.
AB - Cryopreservation of human spermatozoa is a commonly used technique in assisted
reproduction, however freezing low concentrations of sperm while maintaining
adequate post-thaw motility remains a challenge. In an effort to optimize post
thaw motility yields, low volumes of human sperm were frozen in polyimide-coated
fused silica micro-capillaries using 0.065 M, 0.125 M, 0.25 M, or 0.5 M trehalose
as the only cryoprotectant. Micro-capillaries were either initially incubated in
liquid nitrogen vapor before plunging into liquid nitrogen, or directly plunged
into liquid nitrogen. Post thaw sperm counts and motility were estimated.
Spermatozoa that were initially incubated in liquid nitrogen vapor had greater
post thaw motility than those plunged immediately into liquid nitrogen
independent of trehalose concentration. The protective effect of 0.125 M d
glucose, 3-O-methyl-d-glucopyranose, trehalose, sucrose, raffinose, or stachyose
were evaluated individually. Trehalose and sucrose were the most effective
cryoprotectants, recovering 69.0% and 68.9% of initial sperm motility,
respectively.
PMID- 27498217
TI - Awareness of allergic enterocolitis among primary-care paediatricians: A web
based pilot survey.
AB - BACKGROUND: Allergic enterocolitis, also known as food protein-induced
enterocolitis syndrome (FPIES), is an increasingly reported and potentially
severe non-IgE mediated food allergy of the first years of life, which is often
misdiagnosed due to its non-specific presenting symptoms and lack of diagnostic
guidelines. OBJECTIVE: We sought to determine the knowledge of clinical,
diagnostic and therapeutic features of FPIES among Italian primary-care
paediatricians. METHODS: A 16-question anonymous web-based survey was sent via
email to randomly selected primary care paediatricians working in the north of
Italy. RESULTS: There were 194 completed surveys (48.5% response rate). Among
respondents, 12.4% declared full understanding of FPIES, 49% limited knowledge,
31.4% had simply heard about FPIES and 7.2% had never heard about it. When
presented with clinical anecdotes, 54.1% recognised acute FPIES and 12.9%
recognised all chronic FPIES, whereas 10.3% misdiagnosed FPIES as allergic
proctocolitis or infantile colic. To diagnose FPIES 55.7% declared to need
negative skin prick test or specific-IgE to the trigger food, whereas 56.7%
considered necessary a confirmatory oral challenge. Epinephrine was considered
the mainstay in treating acute FPIES by 25.8% of respondents. Only 59.8% referred
out to an allergist for the long-term reintroduction of the culprit food.
Overall, 20.1% reported to care children with FPIES in their practice, with cow's
milk formula and fish being the most common triggers; the diagnosis was self-made
by the participant in 38.5% of these cases and by an allergist in 48.7%.
CONCLUSION: There is a need for promoting awareness of FPIES to minimise delay in
diagnosis and unnecessary diagnostic and therapeutic interventions.
PMID- 27498218
TI - The use of structural modelling to infer structure and function in biocontrol
agents.
AB - Homology modelling can provide important insights into the structures of proteins
when a related protein structure has already been solved. However, for many
proteins, including a number of invertebrate-active toxins and accessory
proteins, no such templates exist. In these cases, techniques of ab initio,
template-independent modelling can be employed to generate models that may give
insight into structure and function. In this overview, examples of both the
problems and the potential benefits of ab initio techniques are illustrated.
Consistent modelling results may indicate useful approximations to actual protein
structures and can thus allow the generation of hypotheses regarding activity
that can be tested experimentally.
PMID- 27498219
TI - Viruses of commercialized insect pollinators.
AB - Managed insect pollinators are indispensable in modern agriculture. They are used
worldwide not only in the open field but also in greenhouses to enhance fruit
set, seed production, and crop yield. Managed honey bee (Apis mellifera, Apis
cerana) colonies provide the majority of commercial pollination although other
members of the superfamily Apoidea are also exploited and commercialized as
managed pollinators. In the recent past, it became more and more evident that
viral diseases play a key role in devastating honey bee colony losses and it was
also recognized that many viruses originally thought to be honey bee specific can
also be detected in other pollinating insects. However, while research on viruses
infecting honey bees started more than 50years ago and the knowledge on these
viruses is growing ever since, little is known on virus diseases of other
pollinating bee species. Recent virus surveys suggested that many of the viruses
thought to be honey bee specific are actually circulating in the pollinator
community and that pollinator management and commercialization of pollinators
provide ample opportunity for viral diseases to spread. However, the direction of
disease transmission is not always clear and the impact of these viral diseases
on the different hosts remains elusive in many cases. With our review we want to
provide an up-to-date overview on the viruses detected in different
commercialized pollinators in order to encourage research in the field of
pollinator virology that goes beyond molecular detection of viruses. A deeper
understanding of this field of virology is urgently needed to be able to evaluate
the impact of viruses on pollinator health and the role of different pollinators
in spreading viral diseases and to be able to decide on appropriate measures to
prevent virus-driven pollinator decline.
PMID- 27498220
TI - Heat exposure on farmers in northeast Ghana.
AB - Environmental health hazards faced by farmers, such as exposure to extreme heat
stress, are a growing concern due to global climate change, particularly in
tropical developing countries. In such environments, farmers are considered to be
a population at risk of environmental heat exposure. The situation is exacerbated
due to their farming methods that involve the use of primitive equipment and hard
manual labour conducted in full sunshine under hot and humid conditions. However,
there is inadequate information about the extent of heat exposure to such
farmers, both at the household and farm levels. This paper presents results from
a study assessing environmental heat exposure on rural smallholder farmers in
Bawku East, Northern Ghana. From January to December 2013, Lascar USB temperature
and humidity sensors and a calibrated Questemp heat stress monitor were deployed
to farms and homes of rural farmers at Pusiga in Bawku East to capture farmers'
exposure to heat stress in both their living and working environments as they
executed regular farming routines. The Lascar sensors have the capability to
frequently, accurately and securely measure temperature and humidity over long
periods. The Questemp heat stress monitor was placed in the same vicinity and
showed strong correlations to Lascar sensors in terms of derived values of wet
bulb globe temperature (WBGT). The WBGT in the working environment of farmers
peaked at 33.0 to 38.1 degrees C during the middle of the day in the rainy
season from March to October and dropped to 14.0-23.7 degrees C in the early
morning during this season. A maximum hourly WBGT of 28.9-37.5 degrees C (March
October) was recorded in the living environment of farmers, demonstrating little
relief from heat exposure during the day. With these levels of heat stress,
exposed farmers conducting physically demanding outdoor work risk suffering
serious health consequences. The sustainability of manual farming practices is
also under threat by such high levels of heat exposure.
PMID- 27498221
TI - Audio-visual speech perception in infants and toddlers with Down syndrome,
fragile X syndrome, and Williams syndrome.
AB - Typically-developing (TD) infants can construct unified cross-modal percepts,
such as a speaking face, by integrating auditory-visual (AV) information. This
skill is a key building block upon which higher-level skills, such as word
learning, are built. Because word learning is seriously delayed in most children
with neurodevelopmental disorders, we assessed the hypothesis that this delay
partly results from a deficit in integrating AV speech cues. AV speech
integration has rarely been investigated in neurodevelopmental disorders, and
never previously in infants. We probed for the McGurk effect, which occurs when
the auditory component of one sound (/ba/) is paired with the visual component of
another sound (/ga/), leading to the perception of an illusory third sound (/da/
or /tha/). We measured AV integration in 95 infants/toddlers with Down, fragile
X, or Williams syndrome, whom we matched on Chronological and Mental Age to 25 TD
infants. We also assessed a more basic AV perceptual ability: sensitivity to
matching vs. mismatching AV speech stimuli. Infants with Williams syndrome failed
to demonstrate a McGurk effect, indicating poor AV speech integration. Moreover,
while the TD children discriminated between matching and mismatching AV stimuli,
none of the other groups did, hinting at a basic deficit or delay in AV speech
processing, which is likely to constrain subsequent language development.
PMID- 27498222
TI - Dietary galactooligosaccharide elicits positive effects on non-specific immune
parameters and growth performance in Caspian white fish (Rutilus frisii kutum)
fry.
AB - An eight-weeks feeding trial was conducted to investigate the effects of
galactooligosaccharide (GOS), on the skin and serum non-specific immune
parameters and growth performance of Caspian white fish (Rutilus frisii kutum)
fry. Fish (2.07 +/- 0.08 g) were fed different levels of GOS (0%, 1%, 2% and 3%).
No significant (P > 0.05) difference was observed in mucus protease activity, but
inclusion of 1% GOS significantly (P < 0.05) elevated total immunoglobulin (Ig)
level and lysozyme activity. Evaluation of serum non-specific immune parameters
revealed significant (P < 0.05) increase in serum total Ig and lysozyme activity
of fish fed 1% or 2% GOS compared those of fish fed control diet. Furthermore,
the serum alternative haemolytic complement activity (ACH50) was significantly (P
< 0.05) elevated in all prebiotic groups regardless of inclusion levels.
Administration of GOS in diet significantly (P < 0.05) improved growth
performance and feed utilisation. The results of the present study revealed that
GOS administration is beneficial by improving immune response and growth
performance of Caspian white fish.
PMID- 27498223
TI - Tobacco exposure and maternal psychopathology: Impact on toddler problem
behavior.
AB - Prenatal exposure to tobacco has consistently predicted later problem behavior
for children. However, little is known about developmental mechanisms underlying
this association. We examined a conceptual model for the association between
prenatal tobacco exposure and child problem behavior in toddlerhood via indirect
paths through fetal growth, maternal depression, and maternal aggressive
disposition in early infancy and via maternal warmth and sensitivity and infant
negative affect in later infancy. The sample consisted of 258 mother-child dyads
recruited during pregnancy and assessed periodically at 2, 9, and 16months of
child age. Pathways via maternal depression and infant negative affect to toddler
problem behavior were significant. Further, combined tobacco and marijuana
exposure during pregnancy and reduced fetal growth also demonstrated important
associations with infant negative affect and subsequent problem behavior. These
results highlight the importance of considering the role of maternal negative
affect and poor fetal growth as risk factors in the context of prenatal exposure.
PMID- 27498224
TI - First Things First: Vital Protein Marks by N-Terminal Acetyltransferases.
AB - N-terminal (Nt) acetylation is known to be a highly abundant co-translational
protein modification, but the recent discovery of Golgi- and chloroplast-resident
N-terminal acetyltransferases (NATs) revealed that it can also be added post
translationally. Nt-acetylation may act as a degradation signal in a novel branch
of the N-end rule pathway, whose functions include the regulation of human blood
pressure. Nt-acetylation also modulates protein interactions, targeting, and
folding. In plants, Nt-acetylation plays a role in the control of resistance to
drought and in regulation of immune responses. Mutations of specific human NATs
that decrease their activity can cause either the lethal Ogden syndrome or severe
intellectual disability and cardiovascular defects. In sum, recent advances
highlight Nt-acetylation as a key factor in many biological pathways.
PMID- 27498227
TI - A rare case of dorsal-cervical spine myeloid sarcoma detected on 18F-FDG PET/CT
scan.
PMID- 27498225
TI - Circadian Oscillators: Around the Transcription-Translation Feedback Loop and on
to Output.
AB - From cyanobacteria to mammals, organisms have evolved timing mechanisms to adapt
to environmental changes in order to optimize survival and improve fitness. To
anticipate these regular daily cycles, many organisms manifest ~24h cell
autonomous oscillations that are sustained by transcription-translation-based or
post-transcriptional negative-feedback loops that control a wide range of
biological processes. With an eye to identifying emerging common themes among
cyanobacterial, fungal, and animal clocks, some major recent developments in the
understanding of the mechanisms that regulate these oscillators and their output
are discussed. These include roles for antisense transcription, intrinsically
disordered proteins, codon bias in clock genes, and a more focused discussion of
post-transcriptional and translational regulation as a part of both the
oscillator and output.
PMID- 27498226
TI - Segmental outflow of aqueous humor in mouse and human.
AB - The main and only modifiable risk factor in glaucoma, the group of usually late
onset progressive and irreversible blinding optic neuropathies, is elevated
intraocular pressure (IOP). The increase in IOP is due to impeded aqueous humor
(AH) outflow through the conventional pathway. The aberrant increased resistance
at the trabecular meshwork (TM), the filter-like region in the anterior eye
chamber is the major contributory factor in causing the impeded outflow. In
normal as well as in glaucoma eyes the regions of the TM are divided into areas
of high and low flow. The collector channels and distal outflow regions are now
increasingly being recognized as potential players in contributing to impede AH
outflow. Structural and molecular make-up contributing to the segmental blockage
to outflow is likely to provide greater insight. Establishing segmental blockage
to outflow in model systems of glaucoma such as the mouse in parallel to human
eyes will expand our repertoire of tools for investigation. Further study into
this area of interest has the potential to ultimately lead to the development of
new therapeutics focused on lowering IOP by targeting the various components of
segmental blockage of outflow in the TM and in the distal outflow region.
PMID- 27498228
TI - Evaluation of a new extraction protocol for yeast identification by mass
spectrometry.
AB - In this paper, we evaluate a rapid and safe pretreatment procedure using glass
beads for MALDI-TOF yeast identification in a routine clinical laboratory
avoiding the use of formic acid. We created a new yeast database library using
1186 yeasts, including 11 references strains. The database was tested using 2131
clinical isolates allowing accurate species-level identification in 98.9%
(2107/2131) of cases with a score over 1.9 and in 99% (2123/2131) of the strains
at the genus level. The new protocol is a rapid, reliable and safe procedure for
the accurate identification of pathogenic Candida strains and requires minimal
handling.
PMID- 27498229
TI - In vivo near-infrared fluorescence imaging of Leishmania amazonensis expressing
infrared fluorescence protein (iRFP) for real-time monitoring of cutaneous
leishmaniasis in mice.
AB - The use of Leishmania amazonensis-infected BALB/c mice is an important model for
the study of experimental cutaneous leishmaniasis. Here we report the development
of a non-invasive method to directly evaluate and measure parasite burden during
the course of the infection, based on the near-infrared fluorescence detection of
a recombinant L. amazonensis strain. So, we generated a L. amazonensis strain
that stably expresses the near-infrared protein (iRFP) gene and compared the
maintenance of its vitro and in vivo characteristics, such as fitness,
pathogenicity and fluorescence emission. After that, we followed the disease
development, as well as the parasite burden in BALB/c mice footpads infected with
L. amazonensis-iRFP, by using an in vivo near-infrared fluorescence scanner. In
vitro results showed a linear correlation between the fluorescence emission and
the number of parasites. The in vivo study showed that the use of iRFP
transfected L. amazonensis enables the monitoring of parasite burden by measuring
fluorescence signals. Therefore, this technique can be confidently used to
directly monitor parasitic load and infection overtime and could be an excellent
tool for in vitro and in vivo screening of anti-leishmanial drugs and vaccine
efficiency. This is the first report of the use of the near-infrared fluorescence
imaging technique for monitoring in vivo cutaneous leishmaniasis.
PMID- 27498230
TI - Characterization of a single-chain variable fragment specific to Cronobacter spp.
from hybridoma based on outer membrane protein A.
AB - Monoclonal antibody and polyclonal antibody specific to Cronobacter spp. had been
reported in previous studies. However, the preparation of single-chain variable
fragment (scFv) was faster and convenient. Hence, the aim of this study was to
construct a scFv using outer membrane protein A (OmpA) of C. sakazakii as
antigen. The protein sequences of OmpA of Cronobacter spp. were analyzed first.
The results showed protein OmpA with length of 347 amino acids was conserved in
Cronobacter genus (94.83%-100% of protein identity) and was greater than that
observed for the other genera tested (8.28-91.64% of protein identity). Then,
purified protein OmpA expressed in E. coli was used to prepare hybridoma and to
construct scFv further. The scFv was named scFvH81 and analyzed by
bioinformatics. The model of scFvH81 built by homologous modeling had a good
quality (residues in disallowed regions: 3%) and showed that scFvH81 had a
standard pocket-like site. Purified scFvH81 was prepared by denaturation and
renaturation of inclusion body and it showed a good specificity and its affinity
of Ka=2.39*10(6)M(-1). Therefore, it could be used in the detection and the
pathogenesis study of Cronobacter spp.
PMID- 27498231
TI - Hybridization accompanying FRET event in labeled natural nucleoside-unnatural
nucleoside containing chimeric DNA duplexes.
AB - Forster resonance energy transfer (FRET) is a highly efficient strategy in
illuminating the structures, structural changes and dynamics of DNA, proteins and
other biomolecules and thus is being widely utilized in studying such phenomena,
in designing molecular/biomolecular probes for monitoring the hybridization event
of two single stranded DNA to form duplex, in gene detection and in many other
sensory applications in chemistry, biology and material sciences. Moreover, FRET
can give information about the positional status of chromophores within the
associated biomolecules with much more accuracy than other methods can yield.
Toward this end, we want to report here the ability of fluorescent unnatural
nucleoside, triazolylphenanthrene ((TPhen)BDo) to show FRET interaction upon
hybridization with fluorescently labeled natural nucleosides, (Per)U or (OxoPy)U
or (Per)U, forming two stable chimeric DNA duplexes. The pairing selectivity and
the thermal duplex stability of the chimeric duplexes are higher than any of the
duplexes with natural nucleoside formed. The hybridization results in a Forster
resonance energy transfer (FRET) from donor triazolylphenanthrene of (TPhen)BDo
to acceptor oxopyrene of (OxoPy)U and/or to perylene chromophore of (Per)U,
respectively, in two chimeric DNA duplexes. Therefore, we have established the
FRET process in two chimeric DNA duplexes wherein a fluorescently labeled natural
nucleoside ((OxoPy)U or (Per)U) paired against an unnatural nucleoside
((TPhen)BDo) without sacrificing the duplex stability and B-DNA conformation. The
hybridization accompanying FRET event in these classes of interacting
fluorophores is new. Moreover, there is no report of such designed system of
chimeric DNA duplex. Our observed phenomenon and the design can potentially be
exploited in designing more of such efficient FRET pairs for useful application
in the detection and analysis of biomolecular interactions and in material
science application.
PMID- 27498232
TI - A new dual-collimation batch reactor for determination of ultraviolet
inactivation rate constants for microorganisms in aqueous suspensions.
AB - We developed, characterized, and tested a new dual-collimation aqueous UV reactor
to improve the accuracy and consistency of aqueous k-value determinations. This
new system is unique because it collimates UV energy from a single lamp in two
opposite directions. The design provides two distinct advantages over traditional
single-collimation systems: 1) real-time UV dose (fluence) determination; and 2)
simple actinometric determination of a reactor factor that relates measured
irradiance levels to actual irradiance levels experienced by the microbial
suspension. This reactor factor replaces three of the four typical correction
factors required for single-collimation reactors. Using this dual-collimation
reactor, Bacillus subtilis spores demonstrated inactivation following the classic
multi-hit model with k=0.1471cm(2)/mJ (with 95% confidence bounds of 0.1426 to
0.1516).
PMID- 27498233
TI - A comparative study on the nanoparticles for improved drug delivery systems.
AB - Nanoparticles have attracted considerable recent interest for diverse biomedical
applications because of the unique properties of the nanomaterials. It is already
known that one of the major advances in the relative application of nanoparticles
is the recognition of the steric stabilization which can increase the particle
stability in the biological environment and provide the opportunities of the
application of nanoparticles in the development of drug delivery systems (DDSs)
for achieving drug targeting and controlled drug release. To facilitate their use
in such applications, the appropriate design of surface ligands on these
nanoparticles is necessary. In view of these, functionalized nanoparticles
through surface modification can be utilized to specifically interact with the
target molecules on the cell membrane or intracellular ones. This review briefly
presents self-assembled nanoparticles with molecules of therapeutic significance
with two strategies. The first strategy attempts to improve the placement of the
drugs using conjugating the appropriate ligands or adding targeting moieties to
the DDS. The second strategy utilizes trigger-controlled drug-release, which
restricts drug release at the targeted site to kill cancer cells by externally
controlled mechanisms. Among external stimulations, conveniently light has
attracted much interest because it, as an orthogonal external stimulus, gives
spatiotemporal control of payload release.
PMID- 27498235
TI - Complete recovery of myocardial inflammation imaged by T2 mapping.
PMID- 27498234
TI - Peromyscus as a model system for human hepatitis C: An opportunity to advance our
understanding of a complex host parasite system.
AB - Worldwide, there are 185 million people infected with hepatitis C virus and
approximately 350,000 people die each year from hepatitis C associated liver
diseases. Human hepatitis C research has been hampered by the lack of an
appropriate in vivo model system. Most of the in vivo research has been conducted
on chimpanzees, which is complicated by ethical concerns, small sample sizes,
high costs, and genetic heterogeneity. The house mouse system has led to greater
understanding of a wide variety of human pathogens, but it is unreasonable to
expect Mus musculus to be a good model system for every human pathogen.
Alternative animal models can be developed in these cases. Ferrets (influenza),
cotton rats (human respiratory virus), and woodchucks (hepatitis B) are all
alternative models that have led to a greater understanding of human pathogens.
Rodent models are tractable, genetically amenable and inbred and outbred strains
can provide homogeneity in results. Recently, a rodent homolog of hepatitis C was
discovered and isolated from the liver of a Peromyscus maniculatus. This
represents the first small mammal (mouse) model system for human hepatitis C and
it offers great potential to contribute to our understanding and ultimately aid
in our efforts to combat this serious public health concern. Peromyscus are
available commercially and can be used to inform questions about the origin,
transmission, persistence, pathology, and rational treatment of hepatitis C.
Here, we provide a disease ecologist's overview of this new virus and some
suggestions for useful future experiments.
PMID- 27498236
TI - Transpulmonary resection of an interventricular septal fibroma in an adult
patient.
PMID- 27498237
TI - Preeclampsia: a fascinating syndrome due not only to oxidative stress.
PMID- 27498239
TI - Pharmacokinetics and biodistribution of squalene-containing emulsion adjuvant
following intramuscular injection of H5N1 influenza vaccine in mice.
AB - Squalene is a component of oil-in-water emulsion adjuvants developed for
potential use in some influenza vaccines. The biodistribution of the squalene
containing emulsion adjuvant (AddaVaxTM) alone and as part of complete H5N1
vaccine was quantified in mechanistically and toxicologically relevant target
tissues up to 336 h (14 days) following injection into quadriceps muscle. At 1 h,
about 55% of the intramuscularly injected dose of squalene was detected in the
local quadriceps muscles and this decreased to 26% at 48 h. Twenty-four hours
after the injection, approximately 5%, 1%, and 0.6% of the injected dose was
detected in inguinal fat, draining lymph nodes, and sciatic nerve, respectively.
The peak concentration for kidney, brain, spinal cord, bone marrow, and spleen
was each less than 1% of the injected dose, and H5N1 antigen did not
significantly alter the biodistribution of squalene to these tissues. The area
under-blood-concentration curve (AUC) and peak blood concentration (Cmax) of
squalene were slightly higher (20-25%) in the presence of H5N1 antigen. A
population pharmacokinetic model-based statistical analysis identified body
weight and H5N1 antigen as covariates influencing the clearance of squalene. The
results contribute to the body of knowledge informing benefit-risk analyses of
squalene-containing emulsion vaccine adjuvants.
PMID- 27498238
TI - The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine
induced epileptic disorders in Wistar rats.
AB - Evidence shows that inflammatory and immune processes within the brain might
account for the pathophysiology of epilepsy. Therefore, developing new
antiepileptic drugs that can modulate seizures through mechanisms other than
traditional drugs is required for the treatment of refractory epilepsy. This
study aims to determine the relationship between brain inflammation and epilepsy,
to examine the contribution of some biochemical parameters involved in brain
inflammation, and to address the effect of pharmacological interventions using
some anti-inflammatory and immunomodulatory drugs in an experimental epilepsy
model. Adult male rats were divided into seven groups of 20. G1 was the normal,
non-treated control. G2 was the epileptic, non-treated group. G3-G7 were treated
with celecoxib, methotrexate, azathioprine, dexamethasone, and valproate,
respectively, for a period of three weeks. Induction of status epilepticus (SE)
by Li-pilocarpine was performed on groups G2-G7. EEG tracing was conducted, and
inflammatory mediators (brain and serum IL-1beta, IL 6, PGE2, HSP70, TGF-beta2,
and IFNgamma) were measured. The induction of SE increased the amplitude and
frequency of EEG tracing and inflammatory mediators more than in the normal
control group. Treatments of epileptic rats reduced the frequency and amplitude
of EEG tracing and significantly decreased the levels of inflammatory mediators
in some treated rats compared to G2. These findings demonstrate that some anti
inflammatory and immunomodulatory drugs can lower the frequency and amplitude of
seizures and reduce some inflammatory mediators in epilepsy treatments,
strengthening the possibility that targeting these immunological and inflammatory
pathways may represent another effective therapeutic approach to preventing
epileptic seizures.
PMID- 27498240
TI - Vessel traffic safety in busy waterways: A case study of accidents in western
shenzhen port.
AB - Throughout the world, busy waterways near large ports witness heavy vessel
traffic in recent decades. The waterways are characterized by high risk in terms
of loss of life, property, and pollution to environment. To facilitate maritime
safety management with satisfactory efficiency and efficacy, the authors propose
a framework of safety indexes to evaluate the risk level in busy waterways
according to the accident severity, fatality rate and special indicators of
maritime transportation. The safety indexes consist of Safety Evaluation Index
(SEI) and Safety Warning Index (SWI), and are derived from the proposed risk
criteria of Chinese vessel traffic. As a case study, data on vessel traffic
accidents reported in the Western Shenzhen Port, South China from 1995 to 2015
are analyzed. The actual risk level of this area during the period is calculated
under the framework. The implementation of the safety indexes indicate that the
risk criteria and safety indexes are practicable and effective for the vessel
traffic management. The methodology based on long-term accident data can
significantly support the risk analysis in the macroscopic perspective for busy
ports and waterways, such that SWI can act as threshold to trigger actions, while
SEI can act as an indicator to measure safety status.
PMID- 27498241
TI - Adult-onset stereotypical motor behaviors.
AB - Stereotypies have been defined as non-goal-directed movement patterns repeated
continuously for a period of time in the same form and on multiple occasions, and
which are typically distractible. Stereotypical motor behaviors are a common
clinical feature of a variety of neurological conditions that affect cortical and
subcortical functions, including autism, tardive dyskinesia, excessive
dopaminergic treatment of Parkinson's disease and frontotemporal dementia. The
main differential diagnosis of stereotypies includes tic disorders, motor
mannerisms, compulsion and habit. The pathophysiology of stereotypies may involve
the corticostriatal pathways, especially the orbitofrontal and anterior
cingulated cortices. Because antipsychotics have long been used to manage
stereotypical behaviours in mental retardation, stereotypies that present in
isolation tend not to warrant pharmacological intervention, as the benefit-to
risk ratio is not great enough.
PMID- 27498242
TI - Corrective limb osteotomy using patient specific 3D-printed guides: A technical
note.
AB - We describe the step-by-step process of a corrective osteotomy using 3D printed
patient specific guides. Before surgery, bilateral computed tomography (CT) scans
are made to plan correction in the affected limb. The digital pre-planning
defines the location of the K-wires, drill holes, and the osteotomy site(s).
Subsequently, a 3D printed patient specific guide is applied, which indicates the
exact position of these drill holes and the osteotomies. This increases the
accuracy of the surgery by means of patient specific fit of the guide. During
surgery an incision is made and the guide is applied on the bone, which allows
the surgeon to perform a very precise osteotomy. Next, the bone is reduced either
directly using the plate and marked drill holes, or indirectly using a second
reduction guide. In the latter case, the previously drilled K-wires are used to
adequately position the reduction guide. Fixation of the bone fragments using
plating osteosynthesis finalizes the process. Although this technique has its
specific limitations, it might serve as a powerful tool in the treatment of
malunion of both articular and nonarticular fractures of the limb.
PMID- 27498243
TI - Manipulation under anesthesia for post traumatic stiff knee-pearls, pitfalls and
risk factors for failure.
AB - BACKGROUND: Stiffness is common following fractures around knee. Manipulation
under anesthesia (MUA) is the initial noninvasive procedure usually performed for
such patients. Though MUA has been extensively evaluated for knee arthroplasty,
there is paucity of literature regarding its benefits in trauma cases. The
purpose of this study was to define the role of manipulation in post traumatic
stiff knees. METHODS: Hospital inpatient and outpatient records from January 2010
to June 2014 were retrospectively reviewed to identify patients undergoing MUA at
our institution. Patients with more than one year follow up and adequate data
were included. Clinical and radiographic parameters were analyzed to assess
outcomes, complications, effect of timing on flexion gain as well as identify
risk factors associated with failure. RESULTS: Out of 45 patients undergoing
manipulation, 41 patients with 48 knees (34 unilateral and 7 bilateral) met
inclusion criteria. Thirty six manipulations were successful while 3 were
abandoned due to tight tissues and 9 developed complications.Successful MUA
resulted in immediate gain of 62.36 degrees of flexion which decreased to 49.86
degrees at 1year. There was statistically significant loss of flexion of 12.5
degrees over a year (p value 0.0013). Arc of motion improved from 48.5 degrees
to 106.1 degrees at 1year (p value <0.0001). Significant improvement was also
seen in extension and fixed flexion deformity (p value <0.0001). No significant
difference could be detected between early (<3 months) and late (>3 months)
groups with respect to outcomes (p value 0.883)or complications (p value 0.3193).
Failed group had significantly lower pre MUA flexion and pre MUA range of motion
(p value 0.003). Univariate analysis showed that extensor mechanism ruptures
during injury (p value <0.0001) and knees with Flexion <40 degrees (p value
0.0022) or ROM<30 degrees (p value 0.0002) were significantly associated with
failures. CONCLUSION: MUA is a suitable non invasive treatment option for post
traumatic stiffness. There is no effect of timing on outcome and late
manipulation also results in good outcome. Extensor mechanism rupture and pre
manipulation ROM<30 degrees or flexion <40 degrees are associated with failure
and such cases should be considered for alternative options for better outcome.
PMID- 27498244
TI - Increasing the reach: Involving local Muslim religious teachers in a behavioral
intervention to eliminate urogenital schistosomiasis in Zanzibar.
AB - In Zanzibar, United Republic of Tanzania, Madrassa schools are influential
institutions, where children and adults can learn about the interpretation of the
Koran. We aimed to explore the involvement of Madrassa teachers for behavior
change interventions in a randomized operational research trial designed to
investigate the impact of multiple approaches to eliminate urogenital
schistosomiasis transmission from Zanzibar. Madrassa teachers performing in the
30 communities of the behavior change study arm were trained in new interactive
and participatory teaching methods by the local behavioral team and provided with
schistosomiasis-teaching tools for teaching about transmission and prevention in
their Madrassa. In July 2014, in a qualitative research study, we conducted 25
semi-structured interviews with Madrassa teachers to find out how they perceived
their involvement in interventions against schistosomiasis. In 2014, 5926 among
the 8497 registered Madrassa students in 30 communities on Unguja and Pemba
islands received health education and participated in interactive behavior change
exercises about schistosomiasis. Madrassa teachers reported that they valued
their inclusion in the study and the opportunity to educate their students about
schistosomiasis transmission, prevention, and treatment. They also perceived
personal and community benefits as a result of their training and strongly
supported the inclusion of additional Madrassa teachers in future intervention
activities. Madrassa teachers are influential in the Zanzibari society, and hence
are important change agents within our community-level behavioral intervention.
They might constitute an untapped resource that can help to expand and increase
acceptance of and participation in schistosomiasis and other neglected tropical
disease control activities in African Muslim communities.
PMID- 27498245
TI - A single low dose of valproic acid in late prenatal life alters postnatal
behavior and glutamic acid decarboxylase levels in the mouse.
AB - RATIONALE: Rodents exposed to valproic acid (VPA) in prenatal life exhibit post
natal characteristics analogous to autism spectrum disorder (ASD). Many previous
studies used relatively high doses of VPA during early pregnancy, potentially
confounding interpretation because the offspring are the 'survivors' of a toxic
insult. Low dose or late gestation exposure has not been widely studied.
OBJECTIVES: We examined the behavioral sequelae of late gestation exposure to low
dose VPA in the mouse. We also examined postnatal levels of glutamic acid
decarboxylase (GAD65 and GAD67) as markers for GABA neurons, because GABA
pathology and subsequent excitatory/inhibitory imbalance is strongly implicated
in ASD. METHODS: Pregnant C57BL/6N mice received a single subcutaneous injection
of 100 or 200mg/kg on gestation day 17. The control group received a saline
injection on the same day. The offspring were tested in a battery of behavioral
tests in adolescence and adulthood. Six brain regions were harvested and GAD65
and GAD67 were measured by western blotting. RESULTS: Compared to saline-exposed
controls, adult mice exposed to prenatal VPA had impaired novel object
exploration and fear conditioning anomalies. GAD67 was decreased in midbrain,
olfactory bulb, prefrontal cortex and increased in cerebellum, hippocampus and
striatum; GAD65 was decreased in all 6 regions. CONCLUSIONS: Our results suggest
that a low dose of VPA in late pregnancy has persistent effects on brain
development, and in particular the GABA system, which may be relevant to ASD.
Further attention to the impact of gestation time and dose of exposure in VPA
induced ASD models is encouraged.
PMID- 27498246
TI - Brain structure alterations and cognitive impairment following repetitive mild
head impact: An in vivo MRI and behavioral study in rat.
AB - Mild traumatic brain injury (mTBI) or concussion is a common health issue.
Several people repeatedly experience head impact milder than that causing
concussion. The present study aimed to confirm the effects of such repeated
impact on the brain structure and cognitive abilities. Rat models were
established by closed skull weight-drop injury. The animals were anesthetized,
subjected to single (s)-sham, s-mTBI, repetitive (r)-sham, and r-mTBI, and
recovery times were recorded. MRI, including T2-weighted and diffusion tensor
imaging (DTI), as well as, neurological severity scores (mNSS) were assessed for
the dynamics of the brain structure and neurological function. Morris water maze
(MWM) was used to evaluate the cognitive function. The histological examination
of r-mTBI rats revealed the basis of structural changes in the brain. There was
no significant difference in the recovery time, MRI, mNSS, and MWM between the s
sham and the s-mTBI groups. Compared with r-sham, r-mTBI induced significant
differences in the following aspects. The recovery time was prolonged and beam
balance test (BBT) in mNSS increased from day 5. MWM performances were worse even
after the BBT was recovered. The volumes of the cortex (CT), hippocampus (HP),
and lateral ventricle had changed from day 5, which reached a maximum at day 14.
Abnormal DTI parameters were observed in CT, corpus callosum, and HP.
Histological analyses showed that both in CT and HP, neuron counts reduced at the
end of the experiment. Altogether, these findings indicate that non-symptomatic
head injury may result in brain atrophy and cognitive impairment when occurred
repeatedly.
PMID- 27498247
TI - Galanin subtype 1 and subtype 2 receptors mediate opposite anxiety-like effects
in the rat dorsal raphe nucleus.
AB - About 40% of the dorsal raphe nucleus (DRN) neurons co-express serotonin (5-HT)
and galanin. Serotonergic pathways from the DRN to the amygdala facilitate
learned anxiety, while those from the DRN to the dorsal periaqueductal grey
matter (DPAG) impair innate anxiety. Previously, we showed that galanin infusion
in the DRN of rats induces anxiolytic effect by impairing inhibitory avoidance
without changing escape behaviour in the elevated T-maze (ETM). Here, we
evaluated: (1) which galanin receptors would be involved in the anxiolytic effect
of galanin in the DRN of rats tested in the ETM; (2) the effects of galanin intra
DRN on panic-like behaviours evoked by electrical stimulation of the DPAG. The
activation of DRN GAL1 receptors by M617 (1.0 and 3.0nmol) facilitated inhibitory
avoidance, whereas the activation of GAL2 receptors by AR-M1896 (3.0nmol)
impaired the inhibitory avoidance in the ETM, suggesting an anxiogenic and an
anxiolytic-like effect respectively. Both agonists did not change escape
behaviour in the ETM or locomotor activity in the open field. The anxiolytic
effect of AR-M1896 was attenuated by the prior administration of WAY100635
(0.18nmol), a 5-HT1A antagonist. Galanin (0.3nmol) administered in the DRN
increased discreetly flight behaviours induced by electrical stimulation of the
DPAG, suggesting a panicolytic effect. Together, our results showed that galanin
mediates opposite anxiety responses in the DRN by activation of GAL1 and GAL2
receptors. The anxiolytic effect induced by activation of Gal2 receptors may
depend on serotonergic tone. Finally, the role of galanin in panic related
behaviours remains uncertain.
PMID- 27498248
TI - Reply to letter by Dyverfeldt and Ebbers regarding the article "Estimation of
turbulent kinetic energy using 4D phase-contrast MRI: Effect of scan parameters
and target vessel size".
PMID- 27498249
TI - Surgical Treatment of Tumors Involving Kidneys With Fusion Anomalies: A
Contemporary Series.
AB - OBJECTIVE: To report a contemporary series of surgically treated patients with
tumors involving kidneys with fusion anomalies. MATERIALS AND METHODS: We
retrospectively reviewed the medical records of all 10 patients treated at a
single tertiary care institution for tumors involving kidneys with fusion
anomalies between the years 2000 and 2015. One patient, diagnosed with lymphoma,
did not undergo surgical treatment and was therefore excluded. Data regarding
patient, tumor, and treatment characteristics were collected and described.
RESULTS: The study cohort included 7 male and 2 female patients, at a median age
of 52 years. Seven patients underwent open partial nephrectomy.
Nephroureterectomy was performed on 2 patients; 1 open and 1 laparoscopic. All
patients had localized disease at diagnosis. Tumor histologies were renal cell
carcinoma in 5 patients, renal oncocytoma in 1 patient, urothelial carcinoma in 2
patients, and a well-differentiated liposarcoma involving the kidney in 1
patient. Accessory blood vessels were identified in 8 of 9 patients. Median
estimated blood loss was 300 mL (interquartile range: 150-1000). Four patients
had postoperative complications, including 3 major (Clavien grade >= 3) and 3
minor (Clavien grade <= 2) complications. During a median follow-up of 19.2
months (interquartile range: 3-34.8), 1 patient with urothelial carcinoma
developed a bladder recurrence. None of the patients developed new-onset chronic
kidney disease during the early postoperative period. CONCLUSION: Localized renal
cortical tumors in kidneys with fusion anomalies may be treated with partial
nephrectomy; however, complication rates are relatively high. Preoperative
imaging of the blood vessels is necessary, as most patients have an accessory
blood supply.
PMID- 27498251
TI - Macromorphoscopic trait expression in a cranial sample from Medellin, Colombia.
AB - Adjusting existing methods of human identification developed by forensic
anthropologists in the United States for use with populations not included in the
original development of an analytical method requires data collection using
contemporary osteological collections from those populations, and an assessment
of the within-group variation present. The primary purpose of this research is to
document cranial macromorphoscopic trait variation using methods previously
developed in the United States in a sample of 244 individuals from Antioquia,
Medellin, Colombia. All individuals are of known age, sex, and birth region. The
complex population and demographic history of Colombia makes ancestry assessment
particularly difficult in that country. To that end, we explore inter-regional
variation throughout Antioquia using birthplace to determine whether forensic
anthropologists can provide finer levels of detail beyond identifying an unknown
set of human remains as 'Colombian' or, more generally, Hispanic. State and local
levels of identification resulting from the varied population histories of each
state within Antioquia permit finer resolution, but only to a degree of
certainty. Artificial neural networks (aNN) correctly classified only 18.6% of a
validation sample, following modest classification accuracies of test/tuning
(11.6%) and training (82.8%) samples to original birthplace. As with most neural
networks, overfitting is an issue with these analyses. To remedy this overfitting
and to document the applicability of aNNs to the assessment of ancestry in
Colombia, we pooled the sample of Colombian data and compared that to modern
American samples. In those analyses, the best aNN model correctly classified
48.4% (validation) of the sample. Given these results, finer levels of analysis
in Colombia are not yet possible using only macromorphoscopic trait data.
PMID- 27498250
TI - A comparison of different human papillomavirus tests in PreservCyt versus
SurePath in a referral population-PREDICTORS 4.
AB - BACKGROUND: Two transport media, PreservCyt and SurePath, are widely used for
cervical cytology screening. There are concerns that they may perform differently
for HPV testing. OBJECTIVES: A comparison of the performance of six different HPV
tests in SurePath and PreservCyt in a referral population using two samples from
each woman. The primary goal was to compare the performance of each test in the
two media. Comparisons between assays and viral load comparisons between media
were secondary aims. STUDY DESIGN: Two cervical samples were collected in random
order at the same visit in women with abnormal cytology. One sample was placed in
20ml of PreservCyt and the other in 10ml of SurePath. Aliquots were taken for 4
DNA based tests: digene HC2 High-Risk HPV DNA Test, Abbott Realtime, BD Onclarity
and Genera PapType, an RNA based test-: Hologic Aptima and a protein test:
OncoHealth. RESULTS: 630 sample pairs were included in the analyses. For all
tests except the protein test sensitivities were in excess of 90% for CIN2+ and
95% for CIN3+ for both media and with no significant differences except for a
lower sensitivity for CIN2+ of Aptima in SurePath (93% vs 98%, P=0.005).
Specificity for 4 weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of
4,963 patients, 3.3%, 1.6%, and 2.9% of patients stayed 1 to 2 weeks, 2 to 4
weeks, and>4 weeks in the ICU, respectively. In-hospital mortality was 11.1%,
26.6%, and 31.0% for patients with 1 to 2 weeks, 2 to 4 weeks, and>4 weeks ICU
stay, respectively. Patients with ICU stays between 1 and 2 weeks had 6 months, 1
year, and 2 year survival rates of 84.4%, 80.0%, and 75.3% after discharge,
respectively. Patients with ICU stay between 2 and 4 weeks had similar 6 months,
1 year, and 2 year survival rates of 84.7%, 79.9%, and 74.1%, respectively. In
contrast, patients with>4 week ICU stays had significantly lower postdischarge
survival rates of 63.3%, 56.4%, and 41.1% at 6 months, 1 year, and 2 years,
respectively. Postoperative stroke conferred the greatest risk of death within 1
year after discharge (odds ratio 7.6, p = 0.0140). CONCLUSIONS: In-hospital
mortality rates post-cardiac surgery correlate with length of ICU stay but appear
to plateau after 4 weeks. However, a>4 week ICU length of stay confers a worse
long-term outcome post-hospital discharge, especially in patients with
postoperative stroke.
PMID- 27498268
TI - Use of McGrath MAC Videolaryngoscope to Assist Transesophageal Echocardiography
Probe Insertion in Intubated Patients.
AB - OBJECTIVES: Transesophageal echocardiography (TEE) probe insertion with the
conventional blind insertion technique may be difficult in anesthetized and
intubated patients. The use of a videolaryngoscope may facilitate the insertion
of the TEE probe. The aim of this study was to compare the conventional technique
with the use of the McGrath MAC videolaryngoscope for TEE probe insertion in
terms of success rate, duration of insertion, and complications in patients
undergoing cardiovascular surgery. DESIGN: A prospective, randomized study.
SETTING: Training and research hospital. PARTICIPANTS: Eighty-six adult patients
undergoing cardiovascular surgery were included. INTERVENTIONS: Eighty-six adult
patients were randomized into 2 groups: conventional group (n = 43) and McGrath
videolaryngoscope group (n = 43). Success rates, duration of insertion,
complications, and hemodynamic changes during insertion were recorded.
MEASUREMENTS AND MAIN RESULTS: The success rate of TEE probe insertion at the
first attempt was higher in the McGrath videolaryngoscope group (90.5%) than in
the conventional group (43.9%) (p = 0.012). The mean duration for successful
insertion of the TEE probe at the first attempt was longer in the McGrath
videolaryngoscope group (24 s v 11 s) (p = 0.016). The total time for successful
insertion of the TEE probe was similar in both groups. Pharyngeal injuries were
observed more frequently in the conventional group (17.1% v 2.4%) (p = 0.037).
The rate of blood presence on the probe tip in the conventional group was higher
than in the McGrath group (21.9% v 4.8%). There were no statistical differences
between the 2 groups in systolic blood pressure, mean arterial pressure,
diastolic blood pressure, and heart rate before and after TEE insertion.
CONCLUSIONS: The use of the McGrath MAC videolaryngoscope for TEE insertion in
cardiovascular surgery patients increases the success rate and reduces pharyngeal
injuries compared to the conventional technique. The use of the McGrath MAC
videolaryngoscope for TEE insertion causes similar hemodynamic changes as in the
conventional blind insertion technique.
PMID- 27498269
TI - Etiologies of Dysphonia.
PMID- 27498270
TI - Air in the Left Heart: A Perilous Situation in the Presence of a Left Ventricular
Assist Device.
PMID- 27498271
TI - Degradation of aniline by heterogeneous Fenton's reaction using a Ni-Fe oxalate
complex catalyst.
AB - A Ni-Fe oxalate complex catalyst was synthesized and characterized by means of
Brunauer-Emmet-Teller (BET) method, scanning electron microscope (SEM) and X-ray
photo-electron spectroscopy (XPS). The catalyst showed good catalytic activity
for aniline degradation by heterogeneous Fenton's reaction, in which the
synergetic index was 9.3. The effects of reaction temperature, catalyst dosage,
hydrogen peroxide concentration and initial pH were investigated. Under the
optimum conditions (T = 293 K, catalyst dosage = 0.2 g/L, H2O2 concentration = 4
mmol/L and initial pH = 5.4), 100% aniline could be removed within 35 min, and
approximately 88% deamination efficiency was achieved in 60 min. The aniline
degradation process followed the pseudo-first-order kinetic (k = 0.177 min(-1))
with activation energy (Ea) of 49.4 kJ mol(-1). Aniline could be removed in a
broad initial pH (3-8) due to the excellent pH-tolerance property of the
catalyst. The detected ammonium ion indicated that deamination occurred during
aniline degradation. It was proposed that deamination synchronized with aniline
removal, and aniline was attacked by free radicals to generate benzoquinonimine
and phenol. This system is promising for the removal of aniline from water.
PMID- 27498272
TI - Activating social strategies: Face-to-face interaction in technology-mediated
citizen science.
AB - The use of crowds in research activities by public and private organizations is
growing under different forms. Citizen science is a popular means of engaging the
general public in research activities led by professional scientists. By
involving a large number of amateur scientists, citizen science enables
distributed data collection and analysis on a scale that would be otherwise
difficult and costly to achieve. While advancements in information technology in
the past few decades have fostered the growth of citizen science through online
participation, several projects continue to fail due to limited participation.
Such web-based projects may isolate the citizen scientists from the researchers.
By adopting the perspective of social strategy, we investigate within a measure
manipulate-measure experiment if motivations to participate in a citizen science
project can be positively influenced by a face-to-face interaction with the
scientists leading the project. Such an interaction provides the participants
with the possibility of asking questions on the spot and obtaining a detailed
explanation of the citizen science project, its scientific merit, and
environmental relevance. Social and cultural factors that moderate the effect
brought about by face-to-face interactions on the motivations are also dissected
and analyzed. Our findings provide an exploratory insight into a means for
motivating crowds to participate in online environmental monitoring projects,
also offering possible selection criteria of target audience.
PMID- 27498273
TI - Rice bodies in the wrist joint.
PMID- 27498274
TI - High serum uric acid is associated to poorly controlled blood pressure and higher
arterial stiffness in hypertensive subjects.
AB - INTRODUCTION: Serum uric acid (SUA) has been associated to incident hypertension
and increased risk of cardiovascular diseases. MATERIALS AND METHODS: Among the
2191 subjects enrolled during the last population survey of the Brisighella Heart
Study, we identified 146 new cases of arterial hypertension and 394 treated but
uncontrolled hypertensive patients with different levels of SUA. Their
hemodynamic characteristics have been compared with those of age- and sex-matched
normotensive (N. 324) and controlled hypertensive (N. 470) subjects. Then, by
logistic regression analysis, we evaluated which factors were associated with a
worse BP control under pharmacological treatment. RESULTS: SUA levels were
significantly higher in untreated hypertensive and uncontrolled hypertensive
patients when compared to normotensives and controlled hypertensive patients.
Pulse wave velocity (PWV) was significantly higher (p<0.001) in undiagnosed and
uncontrolled hypertensive patients, while controlled hypertensive patients had
PWV values comparable to normotensive controls. A similar trend has been observed
for the augmentation index (AI). A worse BP control was associated with SUA
levels (OR 1277, 95% CI 1134-1600 per mg/dL), AI (OR 1066, 95%CI 1041-1092 per
unit), and PWV (OR 1201, 95% CI 1089-1423, per m/s), but not with age, body mass
index, nor estimated glomerular filtration rate. CONCLUSION: Based on our data,
SUA seems to be associated with an inadequate BP control in subjects treated with
antihypertensive drugs, and subjects with both uncontrolled BP and relatively
high SUA levels have also an increased arterial stiffness that (per se) could be
a cause of worse BP control under treatment.
PMID- 27498275
TI - In-depth analysis of protein inference algorithms using multiple search engines
and well-defined metrics.
AB - : In mass spectrometry-based shotgun proteomics, protein identifications are
usually the desired result. However, most of the analytical methods are based on
the identification of reliable peptides and not the direct identification of
intact proteins. Thus, assembling peptides identified from tandem mass spectra
into a list of proteins, referred to as protein inference, is a critical step in
proteomics research. Currently, different protein inference algorithms and tools
are available for the proteomics community. Here, we evaluated five software
tools for protein inference (PIA, ProteinProphet, Fido, ProteinLP, MSBayesPro)
using three popular database search engines: Mascot, X!Tandem, and MS-GF+. All
the algorithms were evaluated using a highly customizable KNIME workflow using
four different public datasets with varying complexities (different sample
preparation, species and analytical instruments). We defined a set of quality
control metrics to evaluate the performance of each combination of search
engines, protein inference algorithm, and parameters on each dataset. We show
that the results for complex samples vary not only regarding the actual numbers
of reported protein groups but also concerning the actual composition of groups.
Furthermore, the robustness of reported proteins when using databases of
differing complexities is strongly dependant on the applied inference algorithm.
Finally, merging the identifications of multiple search engines does not
necessarily increase the number of reported proteins, but does increase the
number of peptides per protein and thus can generally be recommended.
SIGNIFICANCE: Protein inference is one of the major challenges in MS-based
proteomics nowadays. Currently, there are a vast number of protein inference
algorithms and implementations available for the proteomics community. Protein
assembly impacts in the final results of the research, the quantitation values
and the final claims in the research manuscript. Even though protein inference is
a crucial step in proteomics data analysis, a comprehensive evaluation of the
many different inference methods has never been performed. Previously Journal of
proteomics has published multiple studies about other benchmark of bioinformatics
algorithms (PMID: 26585461; PMID: 22728601) in proteomics studies making clear
the importance of those studies for the proteomics community and the journal
audience. This manuscript presents a new bioinformatics solution based on the
KNIME/OpenMS platform that aims at providing a fair comparison of protein
inference algorithms (https://github.com/KNIME-OMICS). Six different algorithms -
ProteinProphet, MSBayesPro, ProteinLP, Fido and PIA- were evaluated using the
highly customizable workflow on four public datasets with varying complexities.
Five popular database search engines Mascot, X!Tandem, MS-GF+ and combinations
thereof were evaluated for every protein inference tool. In total >186 proteins
lists were analyzed and carefully compare using three metrics for quality
assessments of the protein inference results: 1) the numbers of reported
proteins, 2) peptides per protein, and the 3) number of uniquely reported
proteins per inference method, to address the quality of each inference method.
We also examined how many proteins were reported by choosing each combination of
search engines, protein inference algorithms and parameters on each dataset. The
results show that using 1) PIA or Fido seems to be a good choice when studying
the results of the analyzed workflow, regarding not only the reported proteins
and the high-quality identifications, but also the required runtime. 2) Merging
the identifications of multiple search engines gives almost always more confident
results and increases the number of peptides per protein group. 3) The usage of
databases containing not only the canonical, but also known isoforms of proteins
has a small impact on the number of reported proteins. The detection of specific
isoforms could, concerning the question behind the study, compensate for slightly
shorter reports using the parsimonious reports. 4) The current workflow can be
easily extended to support new algorithms and search engine combinations.
PMID- 27498276
TI - Systematic analysis of the lysine acetylome of the pathogenic bacterium
Spiroplasma eriocheiris reveals acetylated proteins related to metabolism and
helical structure.
AB - Post-translational modifications such as acetylation are an essential regulatory
mechanism of protein function. Spiroplasma eriocheiris, with no cell wall and a
helical structure, is a novel pathogen of freshwater crustacean. There is no
other evidence of acylation (such as succinylation and propionylation) except
acetylation genes in S. eriocheiris concise genome. So the acetylation may play
an important role in S. eriocheiris. Here, we conducted the first lysine
acetylome in S. eriocheiris. We identified 2567 lysine acetylation sites in 555
proteins, which account for 44.69% of the total proteins in this bacterium. To
date, this is the highest ratio of acetylated proteins that have been identified
in bacteria. Fifteen types of acetylated peptide sequence motifs were revealed
from the acetylome. Forty-five lysine-acetylated proteins showed homology with
acetylated proteins previously identified from Escherichia coli, Vibrio
parahemolyticus and Mycobacterium tuberculosis. Notably, most proteins in
glycolysis and all proteins in the arginine deiminase system were acetylated.
Meanwhile, the cell skeleton proteins (Fibril and Mrebs) were all acetylated the
observed acetylation also played an important role in cell skeleton formation.
The results imply previously unreported hidden layers of post-translational
regulation in lysine acetylation that define the functional state of Spiroplasma.
BIOLOGICAL SIGNIFICANCE: This is the first time to analyze PTM of Spiroplasma.
This is the highest ratio of acetylated proteins that have been identified in
bacteria. S. eriocheiris lysine acetylome reveals acetylated proteins related to
metabolism and helical structure. These data provide an important resource to
elucidate the role of acetylation in Spiroplasma cellular physiology.
PMID- 27498278
TI - Reply to the Editor- Implantation of permanent devices in patients with Takotsubo
syndrome.
PMID- 27498279
TI - Color Doppler ultrasound assessment of morphology and types of fistulous tracts
in hidradenitis suppurativa (HS).
AB - BACKGROUND: Fistulous tracts in hidradenitis suppurativa (HS) are key signs of
severity and their clinical evaluation alone may be limited for assessing their
presence and morphology. There is also a need to determine the factors that allow
reversibility of the anatomic changes in HS. OBJECTIVE: We sought to categorize
fistulous tracts in HS. METHODS: A retrospective study of color Doppler
ultrasound images of cases with positive clinical and sonographic criteria of HS
with fistulous tracts was performed. The sonographic staging of HS, location, and
anatomic characteristics of the tracts were registered and graded. Statistical
analysis for correlating variables was performed using bivariate and multivariate
studies. RESULTS: In all, 52 patients presenting 96 fistulous tracts met the
criteria. Morphology was defined and a sonographic classification into 3 types of
fistulae was developed. Type 3 concentrated 71% of the cases presenting
communicating tracts, and type 2, 29%. Types 2 and 3 represented 63% of patients
with multiple fistulous tracts. Fistulous tracts types 2 and 3 were significantly
correlated with age 35 years or older and groin location. LIMITATIONS: Ultrasound
cannot detect lesions less than 0.1 mm. CONCLUSION: Fistulous tracts in HS can be
categorized using ultrasound, which may support earlier and more precise
management.
PMID- 27498277
TI - Validation of electromechanical wave imaging in a canine model during pacing and
sinus rhythm.
AB - BACKGROUND: Accurate determination of regional areas of arrhythmic triggers is of
key interest to diagnose arrhythmias and optimize their treatment.
Electromechanical wave imaging (EWI) is an ultrasound technique that can image
the transient deformation in the myocardium after electrical activation and
therefore has the potential to detect and characterize location of triggers of
arrhythmias. OBJECTIVES: The objectives of this study were to investigate the
relationship between the electromechanical and the electrical activation of the
left ventricular (LV) endocardial surface during epicardial and endocardial
pacing and during sinus rhythm as well as to map the distribution of
electromechanical delays. METHODS: In this study, 6 canines were investigated.
Two external electrodes were sutured onto the epicardial surface of the LV. A 64
electrode basket catheter was inserted through the apex of the LV. Ultrasound
channel data were acquired at 2000 frames/s during epicardial and endocardial
pacing and during sinus rhythm. Electromechanical and electrical activation maps
were synchronously obtained from the ultrasound data and the basket catheter,
respectively. RESULTS: The mean correlation coefficient between electromechanical
and electrical activation was 0.81 for epicardial anterior pacing, 0.79 for
epicardial lateral pacing, 0.69 for endocardial pacing, and 0.56 for sinus
rhythm. CONCLUSION: The electromechanical activation sequence determined by EWI
follows the electrical activation sequence and more specifically in the case of
pacing. This finding is of key interest in the role that EWI can play in the
detection of the anatomical source of arrhythmias and the planning of pacing
therapies such as cardiovascular resynchronization therapy.
PMID- 27498280
TI - New Automatic Tools to Identify Responders to Cardiac Resynchronization Therapy.
AB - BACKGROUND: New echocardiographic parameters (apical rocking [AR], septal flash
[SF]) are intended to detect patterns specific to responders to cardiac
resynchronization therapy (CRT). The patterns are visually recognized and
qualitatively described, requiring experience and training. Speckle-tracking
echocardiography can reflect SF and AR by using newly developed, dedicated
parameters, such as start systolic index (SSI) and peak longitudinal displacement
(PLD). The aim of this study was to investigate whether SSI and PLD can identify
potential CRT responders. METHODS: In 125 patients, echocardiograms from before
and 9 +/- 3 months after CRT were retrospectively analyzed with dedicated EchoPAC
prerelease software. From speckle-tracking baseline images, color-coded bull's
eye displays of SSI and PLD were generated. Cutoff values for both parameters
were derived from 25 randomly selected patients and applied to the remaining 100
patients to identify CRT response, defined as a decrease in end-systolic volume
of >=15% during follow-up. The performance of SSI and PLD was compared with the
visual assessment of AR and SF by expert and novice readers. RESULTS: Expert
readers detected 77 patients with AR, identifying CRT responders with sensitivity
and specificity of 85 +/- 2% and 82 +/- 2%, respectively. Novice readers reached
74 +/- 7% sensitivity and 55 +/- 11% specificity, while the sensitivity and
specificity of the quantitative analysis were 72 +/- 3% and 84 +/- 4% for SSI and
80 +/- 1% and 75 +/- 2% for PLD, respectively. CONCLUSIONS: New speckle-tracking
based quantitative assessment of mechanical dyssynchrony by SSI and PLD performs
comparably in identifying CRT responders as visual analysis by expert readers and
performs significantly better than novice readers.
PMID- 27498281
TI - Double-targeted polymersomes and liposomes for multiple barrier crossing.
AB - In order to treat metastasis in the brain, drug delivery systems must overcome
multiple physical barriers between the point of administration and the target,
such as the Blood-brain barrier, that hinder their free access across them.
Multiple targeting approaches arise as a promising alternative to this barrier
and target certain tissues inside the brain at a time. Herein, two surface
modification methods are presented to obtain dual-targeted vesicle-like carriers
functionalized with an MCF-7-specific phage protein and a BBB-specific peptide,
providing the system the ability to cross a BBB model, target breast cancer cells
and deliver its payload. The aim of this study was to compare new designed
polymersomes with liposomes, a well-established delivery vehicle, in terms of
drug loading, targeting, release and tumor cell killing. The bilayer structure of
both systems allowed the conjugation with different ligands both by insertion and
covalent binding. Different behaviour was observed in release, uptake and tumor
cell killing corresponding to differences in membrane permeability of both
vehicles and type of targeting and ligands' combination. Preliminary results
showed that both formulations were able to cross the BBB monolayer without
harming it, showing cytotoxic activity in the abluminal compartment.
PMID- 27498283
TI - Editorial introduction: The effects of somatic disease and environmental insults
on the stress response.
PMID- 27498282
TI - Niosomal approach to brain delivery: Development, characterization and in vitro
toxicological studies.
AB - The majority of active agents do not readily permeate into brain due to the
presence of the blood-brain barrier and blood-cerebrospinal fluid barrier.
Currently, the most innovative and promising non-invasive strategy in brain
delivery is the design and preparation of nanocarriers, which can move through
the brain endothelium. Niosomes can perform brain delivery, in fact polysorbates,
can act as an anchor for apolipoprotein E from blood plasma. The particles mimic
LDL and interact with the LDL receptor leading to the endothelial cells uptake.
The efficacy of niosomes for anticancer therapeutic applications was correlated
to their physicochemical and drug delivery properties. Dimensions and zeta
potential were characterized using dynamic light scattering and asymmetric flow
field fractionation system. Lipid bilayer was characterized measuring the
fluidity, polarity and microviscosity by fluorescent probe spectra evaluation.
Morphology and homogeneity were characterized using atomic force microscopy.
Physicochemical stability and serum stability (45% v/v fetal bovine and human
serum) were evaluated as a function of time using dynamic light scattering. U87
MG human glioblastoma cells were used to evaluate vesicle cytotoxicity and
internalisation efficiency. From the obtained data, the systems appear useful to
perform a prolonged (modified) release of biological active substances to the
central nervous system.
PMID- 27498284
TI - Lactobacillus and lower genital tract infection.
PMID- 27498285
TI - [Acne in Cameroon: Quality of life and psychiatric comorbidities].
AB - BACKGROUND AND AIMS: The impact of acne upon quality of life (QOL) among affected
patients had not previously been investigated in Cameroon. The present study
therefore sought to assess the QOL of patients with acne and related psychiatric
comorbidities in this country. PATIENTS AND METHODS: This was a cross-sectional
study conducted in three hospitals in Yaounde, Cameroon. We included patients
diagnosed with acne after a consultation with a dermatologist, and who consented
to participate in the study. The ECLA scale was used for the clinical evaluation
of acne and the CADI score was used to assess QOL. PHQ-9 and GAD-7 questionnaires
were used for the respective screening of depression and anxiety. RESULTS: We
enrolled 181 patients aged between 13 and 56years. According to the ECLA table,
the acne global severity score ranged from 3 to 26 points. Impairment was
observed in all patients' QOL, which ranged from 1 to 15 points. We noted 11
cases of depression (6.1%) and 14 cases of anxiety (7.7%). There was a positive
and significant correlation between the severity of acne and impairment of
patients' QOL (r=0.46; P<0.001). Likewise, the severity of acne and of depression
and anxiety scores were positively and significantly correlated with one other:
r=0.347 (P<0.001) and r=0.291 (P<0.001), respectively. CONCLUSION: Acne
negatively impacts the QOL of patients presenting acne in Cameroon and is
associated with depression and anxiety, which must therefore be taken into
account when treating these patients.
PMID- 27498286
TI - Response to commentary re 'A critical appraisal of continence in bladder
exstrophy: Long-term outcomes of the complete primary repair'.
PMID- 27498287
TI - Response to Pembrolizumab in a Patient with Relapsing Thymoma.
PMID- 27498288
TI - Slowing the Titanic: China's Epic Struggle with Tobacco.
AB - China is home to a third of the world's smokers and, correspondingly, to a third
of the world's cases of lung cancer. Beginning in the mid-1990s, a generation or
so later than in many Western countries, the Chinese government commenced
measures to control tobacco, limiting advertising, banning smoking in many public
venues, and increasing taxation. At the time of this review, there are signs that
these policies are having some effect, but hundreds of millions of Chinese
continue to smoke and rates of diagnosis of lung cancer continue to rise. There
is much work to be done and much premature death to be suffered before the
epidemic is slowed to the levels reached in Australia or the United States. This
article aims to provide, particularly for practicing lung cancer clinicians, a
description of patterns of smoking in China, the lung cancer epidemic there, and
the stimuli for and barriers to tobacco control imposed by the highly complex and
unique regulatory setting of the Chinese tobacco industry. A particular challenge
in developing this description has come from the variability of studies published
about a huge nation that has enormous diversity in wealth, education,
urbanization, and tradition. The studies vary because the data vary. Much
information on lung cancer and smoking rates in China comes, for example, from
studies of cohorts that may number in the millions yet represent only a small
percentage of the population and sometimes only a tiny geographic area of such a
vast nation. National registry data on lung cancer in China do not yet cover even
a fifth of the national population. Even so, we argue that several major trends
can be identified: (1) more than 50% of men smoke regularly; (2) there are more
than 300 million smokers in China; (3) almost half a million new cases of lung
cancer are diagnosed in China each year; (4) secondhand smoking is a significant
problem in China (as elsewhere), accounting for a high proportion of lung cancer
cases among women, most of whom do not smoke; (5) corrected for age and sex, lung
cancer rates in the Chinese population are as least as high as in Western
countries and arguably higher; and (6) a shift over time from squamous cell
carcinoma (SCC) to adenocarcinoma is occurring in parallel with that noted in
Western populations. Looking to the future, measures to control tobacco in China
are strengthening but remain relatively weak. The reinforcement of control is
hampered by the circumstance that the tobacco industry remains a powerful state
owned monopoly that participates, through its membership of key government
bodies, in the processes that oversee the implementation of tobacco control. The
conflict between the government's dual responsibilities for both the production
and distribution of tobacco and for the implementation of tobacco control carries
inherent contradictions and bias. How long the Chinese government chooses to live
with these contradictions will determine how quickly the smoking of tobacco will
be reduced and how soon the burden of disease that tobacco inflicts on
individuals and society as a whole will be eased.
PMID- 27498289
TI - Overexpression of beta-Catenin and Cyclin D1 is Associated with Poor Overall
Survival in Patients with Stage IA-IIA Squamous Cell Lung Cancer Irrespective of
Adjuvant Chemotherapy.
AB - INTRODUCTION: This study was aimed at understanding the effect of beta-catenin
and cyclin D1 on overall survival in patients with early-stage NSCLC and at
evaluating if the prognostic effect can be modified by adjuvant chemotherapy.
METHODS: We retrospectively analyzed the expression of beta-catenin and cyclin D1
using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 576
patients with early-stage NSCLC. RESULTS: The median duration of follow-up was
5.1 years. Overexpression of beta-catenin and cyclin D1 was found in 56% and 50%
of 576 cases, respectively. Overexpression of beta-catenin and cyclin D1 was
significantly associated with poor overall survival (p = 0.003 and p = 0.0009,
respectively; log rank test) in squamous cell carcinomas, not in adenocarcinomas.
The prognostic significance of each protein in the squamous cell carcinomas was
limited to stages IA, IB, and IIA. In addition, simultaneous overexpression of
beta-catenin and cyclin D1 in the squamous cell carcinomas synergistically
increased hazard ratios (HRs) 15.79 (95% confidence interval [CI] = 1.09-51.23; p
=0.04) for stage IA, 10.30 (95% CI = 2.29-46.41; p = 0.002) for stage 1B, and
3.55 (95% CI = 1.22-10.36; p = 0.02) times for stage 2A compared to those without
overexpression of the two proteins, after adjusting for confounding factors. In
addition, the effect was not dependent on adjuvant chemotherapy. CONCLUSIONS: The
present study suggests that simultaneous overexpression of beta-catenin and
cyclin D1 may be associated with poor overall survival irrespective of platinum
based adjuvant chemotherapy in stage IA-IIA squamous cell carcinoma of the lung.
PMID- 27498290
TI - Assessing cortisol from hair samples in a large observational cohort: The
Whitehall II study.
AB - Hair cortisol concentrations (HCC) have been suggested to reflect long-term
integrated cortisol levels, but most evidence of associations with co-variates is
from small samples of healthy volunteers. The objective of this study was to
describe the collection of hair samples in a large cohort study and report
associations of demographic and health measures with HCC. We examined HCC
measured from the 3cm hair segment near the scalp in 3507 participants (aged 59
83y) from The Whitehall II occupational cohort study of British civil servants.
Hair samples were analysed using a column switching LC-APCI-MS/MS assay. Findings
from mutually adjusted linear regression analyses revealed lower HCC in
participants who reported use of hair dye [% difference (95%CI); -12.5 (-22.0,
1.9), p value=0.022] and evidence suggestive of differences by length of sample
storage and seasonal variation. With regard to demographic variables, HCC was
lower in women compared to men [-17.0 (-24.8, -8.4), p value <0.001] and higher
in Black compared to other ethnic groups. Prevalent diabetes, use of systemic
corticosteroids and cardiovascular medication were independently associated with
higher HCC. With regard to health, depressive symptoms were associated with
higher HCC [20.0 (8.1, 33.3), p value=0.001] following adjustment for physical
disease and medication. We conclude that hair steroid analysis presents
significant opportunities for assessing cortisol in large scale cohorts.
Demographic factors, sample storage, season of collection and hair
characteristics should be considered in future analyses. Health status, both
mental and physical, is linked to HCC.
PMID- 27498291
TI - Impaired brain metabolism and neurocognitive function in childhood leukemia
survivors despite complete hormone supplementation in adulthood.
AB - Cranial radiotherapy is a known risk factor for neurocognitive impairment in
survivors of childhood acute lymphoblastic leukemia (ALL). Understanding the
nature of cognitive dysfunction during adulthood in ALL survivors is important as
it has an impact on major life situations. Thirty-eight (21 women) ALL survivors
were investigated 34 years after diagnosis. Median-age was 38 (27-46) years. All
were treated with a CRT dose of 24Gy and 11 years (3-13) of complete hormone
supplementation. Comparisons were made to 29 matched controls. Assessments of
magnetic resonance spectroscopy (white and grey matter metabolic alterations),
brain volume and neuropsychological tests were performed. ALL survivors
demonstrate a generally lower performance in neuropsychological tests. ALL
survivors scored lower than controls in vocabulary (p<0.001), memory (p<0.001),
learning capacity (p<0.001), spatial ability (p<0.001), executive functions and
attention (p<0.001) 34 years after ALL treatment. Compared to controls ALL
survivors had reduced white matter (WM) (492 vs 536cm3, p<0.001) and grey matter
(GM) volumes (525 vs 555cm3, p=0.001). ALL survivors had lower levels of WM N
acetyl aspartate/creatin (NAA/Cr) (1.48 vs 1.63, p=0.004), WM NAA+NAAG (N
acetylaspartylglutamate)/Cr (1.61 vs 1.85, p<0.001) and lower levels of GM NAA/Cr
(1.18 vs 1.30, p=0.001) and GM NAA+NAAG/Cr (1.28 vs 1.34, p=0.01) compared to
controls. ALL survivors had higher levels in WM MI (Myoinositol)/NAA (0.65 vs
0.56, p=0.01) concentrations compared to controls. There was a significantly
negative correlation of years since ALL diagnosis to WM NAA+NAAG/Cr (r=-0.4,
p=0.04) in ALL survivors. The present study shows impaired brain metabolism
detected by MRS, reduced brain volumes and neurocognitive impairment in childhood
ALL survivors treated with cranial radiotherapy and chemotherapy, despite
complete hormone substitution. We also report an impairment of metabolites
correlated to time since treatment and a progressive impairment in sustained
attention, suggesting an accelerated aging in the irradiated brain. Following
these survivors many decades, or throughout life, after treatment with cranial
radiotherapy and chemotherapy is highly warranted for a broader understanding of
long-term outcome in this patient group.
PMID- 27498294
TI - Rewards boost sustained attention through higher effort: A value-based decision
making approach.
AB - Maintaining sustained attention over time is an effortful process limited by
finite cognitive resources. Recent theories describe the role of motivation in
the allocation of such resources as a decision process: the costs of effortful
performance are weighed against its gains. We examined this hypothesis by
combining methods from attention research and decision neuroscience. Participants
first performed a sustained attention task at different levels of reward. They
then performed a reward-discounting task, measuring the subjective costs of
performance. Results demonstrated that higher rewards led to improved performance
(Exp 1-3), and enhanced attentional effort (i.e. pupil diameter; Exp 2 & 3).
Moreover, discounting curves constructed from the choice task indicated that
subjects devalued rewards that came at the cost of staying vigilant for a longer
duration (Exp 1 & 2). Motivation can thus boost sustained attention through
increased effort, while sustained performance is regarded as a cost against which
rewards are discounted.
PMID- 27498295
TI - Anthocyanins protect from complex I inhibition and APPswe mutation through
modulation of the mitochondrial fission/fusion pathways.
AB - Anthocyanins are a distinguished class of flavonoids with powerful free radical
scavenging activity that have been suggested as chemotherapeutic agents for the
prevention of Alzheimer disease (AD). In this study, we examined the ability of
nutraceutical Medox rich in purified cyanidin 3-O-glucoside (C3G), 3-O-b
glucosides and delphinidin 3-O-glucoside (D3G) to counteract mitochondrial
deficiency induced by complex I inhibition and/or amyloid-beta peptide (Abeta)
induced toxicity. SH-SY5Y neuroblastoma cells were stably transfected with APP
Swedish K670N/M671L double mutation (APPswe) or with the empty vector and treated
with rotenone. We report that Medox treatment improves the metabolic activity and
maintains cell integrity in both cell lines. At the mitochondrial level, APPswe
and rotenone induced mitochondrial fragmentation, an effect that was counteracted
by Medox through the modulation of fission and fusion proteins, resulting in a
reshaped mitochondrial network. Although Medox was unable to fully neutralise the
effects of rotenone on ATP levels and mitochondrial membrane potential, it was
able to prevent rotenone-induced cytotoxicity. Our findings suggest that Medox
anthocyanins, on top of their antioxidant capacity, ameliorate mitochondrial
dysfunction generated by Abeta overproduction or by chemical inhibition of
mitochondrial complex I via stabilization of the fusion/fission processes.
Modulation of the mitochondrial network has been suggested as a novel therapeutic
approach in diseases involving mitochondrial dysfunction and oxidative stress.
Hence, increasing the understanding of how anthocyanins influence mitochondrial
dynamics in a neurodegenerative context, could be of future therapeutic value.
PMID- 27498296
TI - Commentary: Connections across life stages and disease risk: commentary on a
study early in the life course of life course epidemiology.
PMID- 27498293
TI - A nationwide survey of common viral infections in childhood among patients with
primary immunodeficiency diseases.
AB - OBJECTIVES: Patients with primary immunodeficiency diseases (PID) are highly
susceptible to various microorganisms. However, no population-based studies have
been performed among common viral pathogens, such as respiratory syncytial virus
(RSV), rotavirus (RV), varicella-zoster virus (VZV) and influenza virus (IV). The
objective of this study was to reveal the clinical burden of these four
infections among PID patients in Japan. METHODS: We conducted a nationwide survey
by sending questionnaires to 898 hospitals with pediatric departments throughout
Japan. RESULTS: Nine hundred ten PID patients from 621 hospitals were registered
(response rate: 69.2%). Fifty-four of the patients were hospitalized due to these
viral infections. The durations of hospitalization due to RSV and RV infections
differed significantly in the PID patients with and without cellular
immunodeficiency (12.0 vs 6.5 days, p = 0.041; and 14.0 vs 6.0 days, p = 0.031,
respectively). There was no significant difference in the duration of
hospitalization in PID patients with and without cellular immunodeficiency who
were hospitalized with IV infections (7.3 vs 6.1 days, p = 0.53). CONCLUSIONS:
Special attention should be paid to PID patients with compromised cellular
immunity who present with RSV and RV infection due to their high risk for severe
disease.
PMID- 27498292
TI - Known unknowns of cardiolipin signaling: The best is yet to come.
AB - Since its discovery 75years ago, a wealth of knowledge has accumulated on the
role of cardiolipin, the hallmark phospholipid of mitochondria, in bioenergetics
and particularly on the structural organization of the inner mitochondrial
membrane. A surge of interest in this anionic doubly-charged tetra-acylated lipid
found in both prokaryotes and mitochondria has emerged based on its newly
discovered signaling functions. Cardiolipin displays organ, tissue, cellular and
transmembrane distribution asymmetries. A collapse of the membrane asymmetry
represents a pro-mitophageal mechanism whereby externalized cardiolipin acts as
an "eat-me" signal. Oxidation of cardiolipin's polyunsaturated acyl chains -
catalyzed by cardiolipin complexes with cytochrome c. - is a pro-apoptotic
signal. The messaging functions of myriads of cardiolipin species and their
oxidation products are now being recognized as important intracellular and
extracellular signals for innate and adaptive immune systems. This newly
developing field of research exploring cardiolipin signaling is the main subject
of this review. This article is part of a Special Issue entitled: Lipids of
Mitochondria edited by Guenther Daum.
PMID- 27498297
TI - Relationship of childhood weight status to morbidity in adults.
AB - A cohort of white males who had attended elementary schools in Hagerstown, Md.,
between 1923 and 1928, and whose height-weight records for those years were
available, was examined during 1961-63. A study of their childhood relative
weight at ages 9-13, and of their adult relative weight 35-40 years later, was
made in relation to selected physiological variables and diagnosed
morbidity.Essential findings were as follows: Childhood relative weight at ages 9
13 had no significant relationship to adult levels of fasting blood sugar, serum
cholesterol, beta-lipoprotein, or blood pressure, or to cardiovascular renal
disease.Childhood relative weight at ages 9-13 was significantly related to
hypertensive vascular disease. The below average weight group experienced a
higher prevalence than observed in either average or moderately overweight
childhood groups.Approximately 30 percent of the below average weight children
became average weight adults and 21 percent became overweight adults. Of the
average weight children, approximately 40 percent became overweight adults.
Overweight children tended to remain overweight as adults.Adult relative weight
of the same cohort, viewed 35-40 years later, was significantly associated with
fasting blood sugar, beta-lipoprotein, and systolic and diastolic blood pressure.
Elevated levels of each of these variables occurred with greater frequency in the
overweight child.Adult relative weight was significantly associated with
hypertensive vascular disease and cardiovascular renal disease; the higher
prevalence occurred in the overweight adults.The highest risk for hypertensive
vascular and cardiovascular renal disease was associated with the persons who
acquired their overweight status as adults. The higher prevalence of these
diseases among the overweight adults was largely attributable to the adults who
moved from a below average childhood weight category to an overweight adult
group. The moderately or markedly overweight adults who was similarly classified
as a child did not appear to be at greater risk than the average weight adult who
had been an average weight child.
PMID- 27498298
TI - Commentary: Disentangling the contributions of childhood and adult weight to
cardiovascular disease risk.
PMID- 27498299
TI - Gluten Intolerance and Neurodevelopmental Disorders: Is Nitric Oxide the Common
Biomarker Linking These Conditions?
AB - Cruchet et al. attempt to tease out the myths and facts surrounding the growing
popularity of certain dietary approaches in the management of neurodevelopmental
disorders, like attention-deficit hyperactivity disorder (ADHD) and autism
spectrum disorders (ASDs). The authors identify a particular exclusionary-type
approach that seeks to eliminate dietary gluten. Although the relationship
between celiac disease (CD) and ADHD/ASD is not well established, a repeated
clinical feature noted in CD is the elevated levels of nitric oxide in serum and
urine. Elevated oxidative stress has also been observed in neurodevelopmental
conditions, and the author of this correspondence has been the first to propose
that chronic, environmental exposure to the air pollutant, nitrous oxide may
contribute to these oxidative stress profiles through neural cholinergic
perturbation. Therefore, the purpose of this correspondence is to highlight this
biochemical connection between these conditions so as to identify the clinical
populations who may realize the greatest benefit of these dietary approaches,
while minimizing any potential risk of nutrient deficiencies.
PMID- 27498300
TI - Impact of obesity on surgical outcomes of laparoscopic distal pancreatectomy: A
Norwegian single-center study.
AB - BACKGROUND: Obesity is known as a risk factor for intra- and postoperative
complications in pancreatic operation. However, the operative outcomes in obese
patients undergoing laparoscopic distal pancreatectomy remain unclear. METHODS: A
total number of 423 patients underwent laparoscopic distal pancreatectomy at Oslo
University Hospital-Rikshospitalet from April 1997 to December 2015. Patients
were categorized into 3 groups based on the body mass index: normal weight (18.5
24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (>=30 kg/m2). After excluding
underweight patients, 402 patients were enrolled in this study. RESULTS: Obese
patients had significantly longer operative time and increased blood loss
compared with overweight and normal weight patients (190 [61-480] minutes vs 158
[56-520] minutes vs 153 [29-374] minutes, P = .009 and 200 [0-2,800] mL vs 50 [0
6250] mL vs 90 [0-2,000] mL, P = .01, respectively). A multiple linear regression
analysis identified obesity as predictive of prolonged operative time and
increased blood loss during laparoscopic distal pancreatectomy. The rates of
clinically relevant pancreatic fistula and severe complications (>=grade III by
Accordion classification) were comparable in the 3 groups (P = .23 and P = .37,
respectively). A multivariate logistic regression model did not demonstrate an
association between obesity and postoperative morbidity (P = .09). The duration
of hospital stay was comparable in the 3 groups (P = .13). CONCLUSION: In spite
of longer operative time and greater blood loss, laparoscopic distal
pancreatectomy in obese patients is associated with satisfactory postoperative
outcomes, similar to those in normal weight and overweight patients. Hence,
laparoscopic distal pancreatectomy should be equally considered both in obese and
nonobese patients.
PMID- 27498301
TI - Short- and long-term impact of reoperation for complications after major
hepatectomy for hepatocellular carcinoma.
AB - BACKGROUND: The impact of reoperation for complications after major liver
resection for hepatocellular carcinoma was evaluated. METHODS: In this
retrospective study covering 25 years, patients with reoperation for
complications after major liver resection for hepatocellular carcinoma were
compared with patients without reoperation in terms of demographics, tumor
characteristics, operative details, postoperative results, oncologic outcomes,
and survival. Reasons for reoperation were also investigated. RESULTS: Forty-nine
out of 1,092 patients underwent reoperation within a median of 0.2 days (range, 0
6.9 days) after hepatectomy. Patients with and without reoperation had similar
baseline characteristics and liver function. Nonetheless, patients with
reoperation had a higher indocyanine green retention rate at 15 minutes (12.55%
vs 10.5%, P = .015), more operative blood loss (1.4 L vs 1 L, P = .012), a higher
blood transfusion rate (44.9% vs 29.2%, P = .029), longer hospital stay (21 days
vs 11 days, P < .001), a higher hospital mortality (38.8% vs 3.0%, P < .001), and
a higher 90-day mortality (38.8% vs 4.7%, P < .001). Hemorrhage was the most
common cause for reoperation (26/49, 53.1%), mainly resulting from coagulopathic
bleeding from raw areas (12/26, 46.2%) and bleeding from diaphragmatic veins
(6/26, 23.1%). However, reoperation did not affect 5-year overall survival (50.2%
vs 48.3%, P = .468). CONCLUSION: Postoperative hemorrhage was associated with a
high mortality, signifying the importance of meticulous hemostasis and careful
perioperative management. Oncologic outcomes, however, were not affected by
reoperation.
PMID- 27498302
TI - Metabolic syndrome in liver transplantation: A preoperative and postoperative
concern.
AB - BACKGROUND: Metabolic syndrome is increasing among patients undergoing liver
transplantation. Nonalcoholic steatohepatitis is a manifestation of metabolic
syndrome and is an increasingly common cause of end-stage liver disease
necessitating orthotopic liver transplantation. We sought to determine the effect
of preoperative risk factors on the development of post-transplant metabolic
syndrome, complications, readmissions, and mortality. METHODS: We conducted a
review of 114 orthotopic liver transplantations at our institution from May 2012
to April 2014. RESULTS: Patients with (n = 19) and without (n = 95) metabolic
syndrome were similar with regard to age, race, and model for end-stage liver
disease at time of transplant. Donor and operative factors also were similar
between the groups. Preoperative diabetes was found to be associated with an
increased rate of readmission (odds ratio 3.45, P = .03). While preoperative
metabolic syndrome itself was not a significant predictor of worse outcomes,
postoperative metabolic syndrome was associated with significantly greater
readmissions in the first year. Major predictors of new onset metabolic syndrome
after orthotopic liver transplantation included preoperative diabetes and obesity
(odds ratio 8.54 and odds ratio 5.49, P < .01 each). CONCLUSION: Efforts to
decrease the incidence of postoperative metabolic syndrome after orthotopic liver
transplantation may decrease readmissions and improve outcomes, along with
decreasing resource utilization.
PMID- 27498303
TI - Sex, strain, and estrous cycle influences on alcohol drinking in rats.
AB - Although women appear to be more vulnerable to alcohol-induced pathophysiology
than men, the neurobiological basis for sex differences is largely unknown,
partially because most studies on alcohol drinking are conducted in male subjects
only. The present study examined sex differences in alcohol consumption in two
rat strains, Long Evans and Wistar, using multiple behavioral paradigms. The
effects of the estrous cycle on alcohol consumption were monitored throughout the
study. The results indicated that females drank more alcohol than males when
given either continuous or intermittent access to alcohol (vs. water) in their
home cages (voluntary drinking). Under operant conditions, no sex or strain
differences were found in drinking prior to development of alcohol dependence.
However, upon dependence induction by chronic, intermittent alcohol vapor
exposure, Wistar rats of both sexes substantially escalated their alcohol intake
compared with their nondependent drinking levels, whereas Long Evans rats only
exhibited a moderate escalation of drinking. Under these conditions, the estrous
cycle had no effect on alcohol drinking in any strain and drinking model. Thus,
strain, sex, and drinking conditions interact to modulate nondependent and
dependent alcohol drinking. The present results emphasize the importance of
including sex and strain as biological variables in exploring individual
differences in alcohol drinking and dependence.
PMID- 27498304
TI - 6-Aryl-4-amino-pyrimido[4,5-b]indole 2'-deoxyribonucleoside triphosphates (benzo
fused 7-deaza-dATP analogues): Synthesis, fluorescent properties, enzymatic
incorporation into DNA and DNA-protein binding study.
AB - Four 6-substituted 4-amino-pyrimido[4,5-b]indole 2'-deoxyribonucleoside
triphosphates (dA(BX)TPs) were prepared by glycosylation of 4,6
dichloropyrimidoindole followed by ammonolysis, cross-coupling and
triphosphorylation. They were found to be moderate to good substrates for DNA
polymerases in primer extension. They also exerted fluorescence with emission
maxima 335-378nm. When incorporated to oligonucleotide probes, they did not show
significant mismatch discrimination but the 6-benzofuryl 4-amino-pyrimido[4,5
b]indole nucleotide displayed a useful sensitivity to protein binding in
experiment with SSB protein.
PMID- 27498306
TI - Serum granzyme-B, insulin resistance, metabolic syndrome and cardiovascular risk:
statistical validity for risk assessment.
PMID- 27498307
TI - Fast method for simultaneous quantification of tamoxifen and metabolites in dried
blood spots using an entry level LC-MS/MS system.
AB - The purpose of this study was to develop and validate a new liquid chromatography
tandem mass spectrometric (LC-MSMS) assay for the simultaneous quantification of
tamoxifen (TAM) and its main therapeutically active metabolites, N
desmethyltamoxifen (NDT), 4-hydroxytamoxifen (4HT) and endoxifen (END) in dried
blood spots. Ultrasound assisted methanolic extraction was used for TAM and
metabolites extraction from dried blood spot. After evaporation and methanol
reconstitution, the extract was injected into a LC-MSMS system. Reversed phase
chromatography was performed on a C18 grafted column in gradient mode. TAM,
metabolites, and internal standard (diazepam-d5; IS) were identified in positive
electrospray ionization mode using m/z transition of 372.5>72.1 (TAM);
374.23>58.10 (END); 358.27>58.10 (NDT); 388.23>44.80 (4HT) and 290.00>198.00
(IS). Total analytical run time was 6.5min. Assay was linear from 1 to 500ng/mL
for all substances and presented intra and inter-assay precision and accuracy
<15%. TAM, NDT, 4HT and END limits of quantification and detection were of 1 and
0.5ng/mL; 1 and 3ng/mL; 1.7 and 3ng/mL; 0.6 and 2ng/mL, respectively. Recovery
ranged from 83.8 to 96.3% with matrix effect ranged from 4.3 to 29.8% for TAM and
its metabolites. Hematocrit value <=40% appeared to negatively influence accuracy
of the method. In conclusion, the method described here is somewhat accessible,
relatively fast, sensitive and selective with no interference. This assay might
be used to investigate the level of TAM and its metabolites in DBS for
therapeutic drug monitoring purposes.
PMID- 27498305
TI - Polypharmacy and potentially inappropriate medication use in geriatric oncology.
AB - Polypharmacy is a highly prevalent problem in older persons, and is challenging
to assess and improve due to variations in definitions of the problem and the
heterogeneous methods of medication review and reduction. The purpose of this
review is to summarize evidence regarding the prevalence and impact of
polypharmacy in geriatric oncology patients and to provide recommendations for
assessment and management. Polypharmacy has somewhat variably been incorporated
into geriatric assessment studies in geriatric oncology, and polypharmacy has not
been consistently evaluated as a predictor of negative outcomes in patients with
cancer. Once screened, interventions for polypharmacy are even more uncertain.
There is a great need to create standardized interventions to improve
polypharmacy in geriatrics, and particularly in geriatric oncology. The process
of deprescribing is aimed at reducing medications for which real or potential
harm outweighs benefit, and there are numerous methods to determine which
medications are candidates for deprescribing. However, deprescribing approaches
have not been evaluated in older patients with cancer. Ultimately, methods to
identify polypharmacy will need to be clearly defined and validated, and
interventions to improve medication use will need to be based on clearly defined
and standardized methods.
PMID- 27498308
TI - Fabrication and characterization of conductive poly (3,4-ethylenedioxythiophene)
doped with hyaluronic acid/poly (l-lactic acid) composite film for biomedical
application.
AB - Poly 3,4-ethylenedioxythiophene (PEDOT), a polythiophene derivative, has been
proved to be modified by chemical process as biocompatible conductive polymer for
biomedical applications. In this study, novel hyaluronic acid (HA)-doped PEDOT
nanoparticles were synthesized by the method of chemical oxidative
polymerization, then conductive PEDOT-HA/poly(l-lactic acid) (PLLA) composite
films were prepared. The physicochemical characteristics and biocompatibility of
films were further investigated. FTIR, Raman and EDX analysis demonstrated that
HA was successfully doped into PEDOT particles. Cyclic voltammograms indicated
PEDOT-HA particles had favorable electrochemical stability. PEDOT-HA/PLLA films
showed lower surface contact angle and faster degradation degree compared with
PLLA films. Moreover, the cytotoxicity test of PEDOT-HA/PLLA films showed that
neuron-like pheochromocytoma (PC12) cells adhered and spread well on the surface
of PEDOT-HA/PLLA films and cell viability denoted by MTT assay had a significant
increase. PEDOT-HA/PLLA films modified with laminin (LN) also exhibited an
efficiently elongated cell morphology observed by fluorescent microscope and
metallographic microscope. Furthermore, PEDOT-HA/PLLA films were subjected to
different current intensity to elucidate the effect of electrical stimulation
(ES) on neurite outgrowth of PC12 cells. ES (0.5 mA, 2 h) significantly promoted
neurite outgrowth with an average value length of 122 +/- 5 MUm and enhanced the
mRNA expression of growth-associated protein (GAP43) and synaptophysin (SYP) in
PC12 cells when compared with other ES groups. These results suggest that PEDOT
HA/PLLA film combined with ES are conducive to cell growth and neurite outgrowth,
indicating the conductive PEDOT-HA/PLLA film may be an attractive candidate with
ES for enhancing nerve regeneration in nerve tissue engineering.
PMID- 27498310
TI - Growth in salpingectomy rates in the United States since 2000.
PMID- 27498311
TI - Strategies and steps fostering the success of medication management services in
community pharmacies.
AB - OBJECTIVES: To identify and describe the steps and strategies that community
pharmacies with established medication management services have used to integrate
medication management services into their practice settings. DESIGN: Qualitative
case study with semistructured interviews and focus groups. SETTING: Community
pharmacy organizations in Minnesota. PARTICIPANTS: Pharmacists and pharmacy
leadership from 4 different pharmacy organizations including independent, chain,
and health system pharmacies. INTERVENTION: Not applicable. MAIN OUTCOME
MEASURES: Qualitative case study analysis of community pharmacy management and
pharmacists' perceptions of the factors that led to the establishment and
sustainability of their medication management programs. RESULTS: Focus groups and
interviews were undertaken with 25 pharmacists and pharmacy leaders from 4
distinct community pharmacy organizations from April to June 2015. Five themes
emerged, representing specific implementation and continuation stages of
medication management services in community practice: Deciding to Act, Setting
the Stage, Executing the Service, Sticking to It, and Continuing to Grow.
CONCLUSION: This study sheds light on key stages that have commonly occurred
across community pharmacies that are delivering medication management services.
The results of this work may serve as a road map for other community pharmacies
looking to integrate medication management services into their own practice
settings.
PMID- 27498312
TI - Establishing a clinical pharmacy technician at a United States Army military
treatment facility.
AB - OBJECTIVES: To describe the creation of a clinical pharmacy technician position
within the U.S. Army and to identify the personal skills and characteristics
required to meet the demands of this role. SETTING: An outpatient military
treatment facility located in Maryland. PRACTICE DESCRIPTION: The clinical
pharmacy technician position was designed to support clinical pharmacy services
within a patient-centered medical home. PRACTICE INNOVATION: Funding and a
position description were established to hire a clinical pharmacy technician.
Expected duties included administrative (45%), patient education (30%), and
dispensing (25%). Local policy, in accordance with federal law and U.S. Army
regulations, was developed to define the expanded technician responsibility to
deliver patient medication education. RESULTS: In the initial 3 months, the
clinical pharmacy technician spent 24 hours per week on clinical activities,
affording an additional 10-15 hours per week for clinical pharmacists to provide
patient care. Completed consults increased from 41% to 56%, and patient
pharmacist encounters increased from 240 to 290 per month. The technician, acting
as a clinical pharmacist extender, also completed an average of 90 patient
encounters independently each month. As a result of these improvements, the
decision was made to hire a second technician. Currently, the technicians spend
28-40 hours per week on clinical activities, offsetting an average of 26 hours
per week for the clinical pharmacists. CONCLUSION: A patient-centered medical
home clinical pharmacy technician can reduce the administrative workload for
clinical pharmacists, improve their efficiency, and enhance the use of clinical
pharmacy services. Several characteristics, particularly medication knowledge,
make pharmacy technicians particularly suited for this role. The results from the
implementation of a clinical pharmacy technician at this military treatment
facility resulted in an Army-wide expansion of the position and suggested
applicability in other practice sites, particularly in federal pharmacies.
PMID- 27498309
TI - Evaluation of the urinary microbiota of women with uncomplicated stress urinary
incontinence.
AB - BACKGROUND: Female urinary microbiota are associated with urgency urinary
incontinence and response to medication. The urinary microbiota of women with
stress urinary incontinence has not been described. OBJECTIVE: We sought to study
the cross-sectional relationships between urinary microbiota features and
demographic and clinical characteristics of women undergoing stress urinary
incontinence surgery. STUDY DESIGN: Preoperative urine specimens were collected
from women without urinary tract infection and were available from 197 women (174
voided, 23 catheterized) enrolled in a multicenter prospective randomized trial,
the Value of Urodynamic Evaluation study. Demographic and clinical variables were
obtained including stress and urgency urinary incontinence symptoms, menopausal
status, and hormone use. The bacterial composition of the urine was qualitatively
assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic
relatedness and microbial alpha diversity were compared to demographics and
symptoms using generalized estimating equation models. RESULTS: The majority of
197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was
significantly associated with higher body mass index (P = .02); increased
Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04);
and hormonal status (P < .001). No associations were detected with stress urinary
incontinence symptoms. Increased diversity was also associated with a concomitant
lower frequency of Lactobacillus in hormone-negative women. CONCLUSION: Women
undergoing stress urinary incontinence surgery have detectable urinary
microbiota. This cross-sectional analysis revealed that increased diversity of
the microbiota was associated with urgency urinary incontinence symptoms,
hormonal status, and body mass index. In contrast, the female urinary microbiota
were not associated with stress urinary incontinence symptoms.
PMID- 27498313
TI - High lipid accumulation in Yarrowia lipolytica cultivated under double limitation
of nitrogen and magnesium.
AB - Yarrowia lipolytica cultivated under double nitrogen and magnesium limitation,
but not under single nitrogen or single magnesium limitation, produced 12.2g/l
biomass containing 47.5% lipids, which corresponds to a lipid production 5.8g/l.
These yields are the higher described in the literature for wild strains of Y.
lipolytica. Transcription of ACL1 and ACL2, encoding for ATP-citrate lyase
(ATP:CL) was observed even under non-oleaginous conditions but high activity of
ATP:CL was only detected under oleaginous conditions induced by low or zero
activity of NAD(+) dependent isocitrate dehydrogenase. The low activity of malic
enzyme (ME), a NADPH donor in typical oleaginous microorganisms, indicated that
ME may not be implicated in lipid biosynthesis in this yeast, and NADPH may be
provided by the pentose phosphate pathway (PPP). These findings underline the
essential role of magnesium in lipogenesis, which is currently quite unexplored.
The presence of organic nitrogen in low concentrations during lipogenesis was
also required, and this peculiarity was probably related with the PPP
functioning, being the NADPH donor of lipogenic machinery in Y. lipolytica.
PMID- 27498314
TI - In vitro models of medulloblastoma: Choosing the right tool for the job.
AB - The recently-defined four molecular subgroups of medulloblastoma have required
updating of our understanding of in vitro models to include molecular
classification and risk stratification features from clinical practice. This
review seeks to build a more comprehensive picture of the in vitro systems
available for modelling medulloblastoma. The subtype classification and molecular
characterisation for over 40 medulloblastoma cell-lines has been compiled, making
it possible to identify the strengths and weaknesses in current model systems.
Less than half (18/44) of established medulloblastoma cell-lines have been
subgrouped. The majority of the subgrouped cell-lines (11/18) are Group 3 with
MYC-amplification. SHH cell-lines are the next most common (4/18), half of which
exhibit TP53 mutation. WNT and Group 4 subgroups, accounting for 50% of patients,
remain underrepresented with 1 and 2 cell-lines respectively. In vitro modelling
relies not only on incorporating appropriate tumour cells, but also on using
systems with the relevant tissue architecture and phenotype as well as normal
tissues. Novel ways of improving the clinical relevance of in vitro models are
reviewed, focusing on 3D cell culture, extracellular matrix, co-cultures with
normal cells and organotypic slices. This paper champions the establishment of a
collaborative online-database and linked cell-bank to catalyse preclinical
medulloblastoma research.
PMID- 27498315
TI - Modulation of heterologous expression from PBAD promoter in Escherichia coli
production strains.
AB - Promoter PBAD is frequently used for heterologous gene expression due to several
advantages, such as moderately high expression levels, induction by an
inexpensive and non-toxic monosaccharide L-arabinose and tight regulation of
transcription, which is particularly important for expression of toxic proteins.
A drawback of this promoter is all-or-none induction that occurs at subsaturating
inducer concentrations. Although the overall expression level of the cell culture
seems to correlate with increasing arabinose concentrations, the population is a
mixture of induced and uninduced cells and with increasing arabinose
concentrations, only the fraction of induced cells increases. This phenomenon is
caused by autocatalytic gene expression - the expression of the arabinose
transporter AraE is induced by the transported molecule. In this work the
promoter PE, controlling the expression of araE, was exchanged for the stronger
PBAD promoter in two Escherichia coli strains commonly used for heterologous
protein production. This modification should increase a basal number of arabinose
transporters in the cell wall and reduce the threshold concentration required for
induction and thus reduce heterogeneity of cell population. Heterogeneity and
level of expression in individual cells were analysed by flow cytometry using gfp
as a reporter gene. In the strain BL21ai, the promoter exchange increased the
number of induced cells at subsaturating arabinose concentrations as well as a
yield of protein at saturating inducer concentration. In contrast, the
modification did not improve these characteristics in RV308ai. In both strains it
was possible to modulate the expression level in induced cells 3-6-fold even at
subsaturating arabinose concentrations.
PMID- 27498316
TI - A superstructure-based electrochemical assay for signal-amplified detection of
DNA methyltransferase activity.
AB - DNA methyltransferase (MTase) activity is highly correlated with the occurrence
and development of cancer. This work reports a superstructure-based
electrochemical assay for signal-amplified detection of DNA MTase activity using
M.SssI as an example. First, low-density coverage of DNA duplexes on the surface
of the gold electrode was achieved by immobilized mercaptohexanol, followed by
immobilization of DNA duplexes. The duplex can be cleaved by BstUI endonuclease
in the absence of DNA superstructures. However, the cleavage is blocked after the
DNA is methylated by M.SssI. The DNA superstructures are formed with the addition
of helper DNA. By using an electroactive complex, RuHex, which can bind to DNA
double strands, the activity of M.SssI can be quantitatively detected by
differential pulse voltammetry. Due to the high site-specific cleavage by BstUI
and signal amplification by the DNA superstructure, the biosensor can achieve
ultrasensitive detection of DNA MTase activity down to 0.025U/mL. The method can
be used for evaluation and screening of the inhibitors of MTase, and thus has
potential in the discovery of methylation-related anticancer drugs.
PMID- 27498317
TI - Electrochemical detection of Nanog in cell extracts via target-induced resolution
of an electrode-bound DNA pseudoknot.
AB - Nanog is among the most important indicators of cell pluripotency and self-renew,
so detection of Nanog is critical for tumor assessment and monitoring of clinical
prognosis. In this work, a novel method for Nanog detection is proposed by using
electrochemical technique based on target-induced conformational change of an
electrode-bound DNA pseudoknot. In the absence of Nanog, the rigid structure of
the pseudoknot will minimize the connection between the redox tag and the
electrode, thus reducing the obtained faradaic current. Nevertheless, the Nanog
binding may liberate the flexible single-stranded element that transforms the DNA
pesudokont into DNA hairpin structure due to steric hindrance effect, thus making
the electrochemical tag close to the electrode surface. Consequently, electron
transfer can be enhanced and very well electrochemical response can be observed.
By using the proposed method, Nanog can be determined in a linear range from 2nM
to 25nM with a detection limit of 163 pM. Furthermore, the proposed method can be
directly used to assay Nanog not only in purified samples but also in complex
media (cell extracts), which shows potential applications in Nanog functional
studies as well as clinical diagnosis in the future.
PMID- 27498318
TI - Fluorescent imaging of Au(3+) in living cells with two new high selective Au(3+)
probes.
AB - Two new acetylenic compounds were designed and synthesized as the probes to
realize the detection and recognition of Au(3+). The latent fluorophores was
rearranged into the fluorescent coumarin derivatives with strong fluorescence by
a gold ion-mediated hydroarylation reaction. In the meanwhile, the generated
fluorescent substances were also isolated and characterized. The probes
identified Au(3+) ions highly selectively over other biologically relevant metal
ions, and detection concentration of Au(3+) was as low as 0.1uM or less.
Fluorescent imaging of Au(3+) in living cells was also successfully demonstrated.
PMID- 27498319
TI - Hotspots engineering by grafting Au@Ag core-shell nanoparticles on the Au film
over slightly etched nanoparticles substrate for on-site paraquat sensing.
AB - Paraquat (PQ) pollutions are ultra-toxic to human beings and hard to be
decomposed in the environment, thus requiring an on-site detection strategy.
Herein, we developed a robust and rapid PQ sensing strategy based on the surface
enhanced Raman scattering (SERS) technique. A hybrid SERS substrate was prepared
by grafting the Au@Ag core-shell nanoparticles (NPs) on the Au film over slightly
etched nanoparticles (Au FOSEN). Hotspots were engineered at the junctions as
indicated by the finite difference time domain calculation. SERS performance of
the hybrid substrate was explored using p-ATP as the Raman probe. The hybrid
substrate gives higher enhancement factor comparing to either the Au FOSEN
substrate or the Au@Ag core-shell NPs, and exhibits excellent reproducibility,
homogeneity and stability. The proposed SERS substrates were prepared in batches
for the practical PQ sensing. The total analysis time for a single sample,
including the pre-treatment and measurement, was less than 5min with a PQ
detection limit of 10nM. Peak intensities of the SERS signal were plotted as a
function of the PQ concentrations to calibrate the sensitivity by fitting the
Hill's equation. The plotted calibration curve showed a good log-log linearity
with the coefficient of determination of 0.98. The selectivity of the sensing
proposal was based on the "finger print" Raman spectra of the analyte. The
proposed substrate exhibited good recovery when it applied to real water samples,
including lab tap water, bottled water, and commercially obtained apple juice and
grape juice. This SERS-based PQ detection method is simple, rapid, sensitive and
selective, which shows great potential in pesticide residue and additives abuse
monitoring.
PMID- 27498320
TI - Superhydrophilic cotton thread with temperature-dependent pattern for sensitive
nucleic acid detection.
AB - Cotton thread is promising in fabricating biosensors for diagnostic application
due to its excellent characteristics. However, the enrichment of the capture
molecules on a narrow zone of the cotton thread based biosensor is a big
challenge because of its superhydrophilicity. Here, we report a simple, low-cost
and accurate cotton thread based nucleic acid biosensor with temperature
dependent pattern. Liquid wax is used to fabricate temperature-dependent pattern
to restrict the test zone in a narrow area. This biosensor enables visual and
quantitative detection of target DNA by accumulation of gold nanoparticles (GNPs)
on the test zone with a detection limits of 0.75nM. In addition, the cotton
thread based biosensor needs less sample than previous reported lateral flow
strip and the sample solution wicks faster at the cotton thread which can lead to
a shorter detection time. This simple, low-cost and fast detection method holds
great potential to improve healthcare services in the developing regions.
PMID- 27498322
TI - Binding induced colocalization activated hybridization chain reaction on the
surface of magnetic nanobead for sensitive detection of adenosine.
AB - Herein, a sensitive and enzyme-free assay for adenosine detection has been
developed on the basis of binding induced colocalization activated hybridization
chain reaction (HCR) strategy on the surface of magnetic nanobead. First, the
recognition probe was fabricated and divided into two parts: the Apt-1 that
composed a part of adenosine aptamer and toehold domain, and the Apt-2 that
consisted of another part of adenosine aptamer and branch migration domain. The
Apt-1 was immobilized on a streptavidin-magnetic nanobead (streptavidin-MNBs)
that played the roles of enrichment and separation. Then the recognition event of
adenosine could bring the two parts of aptamer together and induce the
colocalization of toehold domain and branch migration domain, which could serve
as an integrated initiator to trigger the HCR, producing a long nicked double
stranded polymer. Finally, the intercalating dye SYBR Green I was inserted into
the polymer, generating an enhanced fluorescence signal. In this strategy, the
initiator was divided into two parts and could be suppressed effectively in the
absence of adenosine. Utilizing the separated function, the spontaneous
hybridization of H1 and H2 could be avoided, and a low background could be
acquired. Moreover, through the double amplification of HCR and multimolecules
binding of SYBR Green I, highly sensitive and enzyme-free detection were
achieved. The detection limit for adenosine detection was 2.0*10(-7)mol/L, which
was comparable or superior to the previous aptasensors. Importantly, adenosine
analysis in human urines has been performed, and this strategy could
significantly distinguish the adenosine content in normal human urines and cancer
patient urines, suggesting that this proposed assay will become a reliable and
sensitive adenosine detection method in early clinical diagnosis and medical
research.
PMID- 27498321
TI - Hemin on graphene nanosheets functionalized with flower-like MnO2 and hollow AuPd
for the electrochemical sensing lead ion based on the specific DNAzyme.
AB - Herein, integrated with DNAzyme highly specific to metal ions, hemin@reduced
graphene oxide (hemin@rGO) functionalized with flower-like MnO2 and hollow AuPd
(hAuPd-fMnO2-hemin@rGO) was used as electroactive probe and electrocatalyst to
construct a universal platform for metal ion detection (lead ion Pb(2+) as the
model). The proposed strategy with generality was mainly based on two aspects.
Firstly, the designed probe not only showed high stability and excellent
peroxidase-like activity originating from hemin, fMnO2 and hAuPd, but also
possessed intrinsic redox performance from hemin, which resulted in the promotion
of electron transfer and the enhancement of the response signal readout.
Secondly, due to the introduction of Pb(2+), Pb(2+)-dependent DNAzyme bound in
the electrode surface could be specifically identified and cleaved by Pb(2+), and
the remained fragment (its supplementary sequence is a single-strand DNA S3)
captured the nanocomposites S3-hAuPd-fMnO2-hemin@rGO by the hybridization
reaction. Therefore, combined the cooperative catalysis of fMnO2, hAuPd and hemin
to H2O2 reduction with highly specific interaction of Pb(2+)-dependent DNAzyme,
the proposed Pb(2+) biosensor showed significant improvement of electrochemical
analytical performance, which was involved in wide dynamic response in the range
of 0.1pM-200nM, low detection limit of 0.034pM, high sensitivity and high
specificity. This could facilitate the universal strategy to be a promising
method for detection of other metal ions, only changing the corresponding DNAzyme
specific to them.
PMID- 27498323
TI - Paper-based fluorescent sensor for rapid naked-eye detection of
acetylcholinesterase activity and organophosphorus pesticides with high
sensitivity and selectivity.
AB - Various strategies have been proposed for the sensing of acetylcholinesterase
(AChE) activity and organophosphorus pesticides (OPs). However, the practical
application of most methods is restricted by their intrinsic drawbacks such as
complexity, long analysis time, and high cost. Thus, it is highly desirable to
develop simple, fast and sensitive approaches for AChE activity and OPs
detection. Herein, we reported a simple paper-based fluorescent sensor (PFS)
based on the aggregation induced emission (AIE) effect of tetraphenylethylene
(TPE) and the addition reaction capability of maleimide, which has been used as a
powerful tool for rapid naked-eye detection of AChE activity and OPs. The
introduction of TPE provides the probe with unique fluorescence property in solid
state and is of great importance for improving the sensitivity of PFS. The
hydrolysis product of acetylthiocholine catalyzed by AChE induced the maleimide
ring destruction and activated the fluorescence performance of TPE. Given that
AChE activity can be specifically inhibited by OPs, the as-proposed PFS can also
be utilized for sensitive detection of OPs. Meanwhile, the variation of
fluorescence signal can be readily detected by naked eyes, and low detection
limits of 2.5mUmL(-1) and 0.5ngmL(-1) for AChE activity and OPs are obtained,
respectively. Moreover, it has been successfully applied for AChE activity and
OPs detection in diluted human serum samples, showing its great potential to be
applied in real samples. Thus, this strategy possesses considerable advantages of
simplicity, rapid detection, portability, cost efficiency and visualization.
PMID- 27498324
TI - Terbium ion-coordinated carbon dots for fluorescent aptasensing of adenosine 5'
triphosphate with unmodified gold nanoparticles.
AB - This work reports on a novel time-resolved fluorescent aptasensing platform for
the quantitative monitoring of adenosine 5'-triphosphate (ATP) by interaction of
dispersive/agglomerate gold nanoparticles (AuNPs) with terbium ion-coordinated
carbon dots (Tb-CDs). To construct such a fluorescent nanoprobe, Tb-CDs with high
efficient fluorescent intensity are first synthesized by the microwave method
with terbium ions (Tb(3+)). The aptasensing system consists of ATP aptamer, AuNP
and Tb-CD. The dispersive/agglomerate gold nanoparticles are acquired through the
reaction of the aptamer with target ATP. Upon target ATP introduction, the
aptamers bind with the analytes to form new aptamer-ATP complexes and coat on the
surface of AuNPs to inhibit their aggregation in the high salt solution. In this
case, the fluorescent signal of Tb-CDs is quenched by the dispersive AuNPs on the
basis of the fluorescence resonance energy transfer (FRET). At the absence of
target analyte, gold nanoparticles tend to aggregate in the high salt state even
if the aptamers are present. Thus, the added Tb-CDs maintain their intrinsic
fluorescent intensity. Experimental results indicated that the aptasensing system
exhibited good fluorescent responses toward ATP in the dynamic range from 40nM to
4.0MUM with a detection limit of 8.5nM at 3sblank criterion. The repeatability
and intermediate precision is less than 9.5% at three concentrations including
0.04, 0.4 and 2.0MUM ATP. The selectivity was acceptable toward guanosine 5'
triphosphate, uridine 5'-triphosphate and cytidine 5'-triphosphate. The
methodology was applied to evaluate the blank human serum spiked with target ATP,
and the recoveries (at 3 concentration levels) ranged between 97.0% and 103.7%.
Importantly, this detection scheme is rapid, simple, cost-effective, and does not
require extensive sample preparation or separation.
PMID- 27498325
TI - Target-catalyzed autonomous assembly of dendrimer-like DNA nanostructures for
enzyme-free and signal amplified colorimetric nucleic acids detection.
AB - Self-assembly of DNA nanostructures is of great importance in nanomedicine,
nanotechnology and biosensing. Herein, a novel target-catalyzed autonomous
assembly pathway for the formation of dendrimer-like DNA nanostructures that only
employing target DNA and three hairpin DNA probes was proposed. We use the sticky
ended Y shape DNA (Y-DNA) as the assembly monomer and it was synthesized by the
catalyzed hairpin assembly (CHA) instead of the DNA strand annealing method. The
formed Y-DNA was equipped with three ssDNA sticky ends and two of them were
predesigned to be complementary to the third one, then the dendrimer-like DNA
nanostructures can be obtained via an autonomous assembly among these sticky
ended Y-DNAs. The resulting nanostructure has been successfully applied to
develop an enzyme-free and signal amplified gold nanoparticle (AuNP)-based
colorimetric nucleic acids assay.
PMID- 27498326
TI - DNA-based hybridization chain reaction and biotin-streptavidin signal
amplification for sensitive detection of Escherichia coli O157:H7 through ELISA.
AB - This study reported on a novel sandwich enzyme linked immunosorbent assay (ELISA)
for the sensitive determination of Escherichia coli O157:H7 (E. coli O157:H7) by
using DNA-based hybridization chain reaction (HCR) and biotin-streptavidin signal
amplification. The anti-E. coli O157:H7 polyclonal antibody (pAb) was immobilized
in the ELISA wells. The anti-E. coli O157:H7 monoclonal antibody (mAb) and
initiator strand (DNA1) were labeled on gold nanoparticle (AuNP) to form a mAb
AuNP-DNA1 complex. In the presence of the target E. coli O157:H7, the sandwiched
immunocomplex, which is pAb-E. coli O157:H7-mAb-AuNP-DNA1, could be formed. Two
types of biotinylated hairpin were subsequently added in the ELISA well. A nicked
double-stranded DNA (dsDNA) that contained abundant biotins was formed after HCR.
Detection was performed after adding horseradish peroxidase-streptavidin and
substrate/chromogen solution. Under optimal conditions, E. coli O157:H7 could be
detected in the range of 5*10(2) CFU/mL to 1*10(7) CFU/mL; the limit of detection
was 1.08*10(2) CFU/mL in pure culture. The LOD of the novel ELISA was 185 times
lower than that of traditional ELISA. The proposed method is considerably
specific and can be applied in the detection of whole milk samples inoculated
with E. coli O157:H7. The coefficient of variation of in pure culture and in
whole milk was 0.99-5.88% and 0.76-5.38%, respectively. This method offers a
promising application in the detection of low concentrations of food-borne
pathogens.
PMID- 27498327
TI - One-step multiplexed detection of foodborne pathogens: Combining a quantum dot
mediated reverse assaying strategy and magnetic separation.
AB - A rapid and multiplexed immunosensor was developed based on a quantum dot (QD)
reverse assaying strategy (RAS) and immuno-magnetic beads (IMBs) for one-step and
simultaneous detection of Escherichia coli O157: H7 and Salmonella. In a
conventional QD-based immunosensor, the fluorescence signal of the "IMBs-target
QD" immunoconjugate is directly used as the assaying readout. However, the
fluorescence signal is affected by IMBs due to light scattering and the "IMBs
target-QD" immunoconjugate needs multiple washing and re-suspension steps. To
address these problems, we use the surplus QD-antibody conjugate as signal
readout in the RAS, which prevents interference from the IMBs, increases the
fluorescence signal, and avoids complex operations. Compared with conventional QD
based immunosensor, the sensitivity of QD-RSA immunosensor for detection of
Escherichia coli O157: H7 has been improved fifty-fold, and whole analysis
procedure can be finished within 1h. Therefore, this RSA strategy is promising
for improving the performance of QD-based immunosensors and could greatly broaden
their applications.
PMID- 27498328
TI - Easy and rapid multi-pass detection of antigen and antibody with micro-lens
sensors.
AB - We introduce a micro-lens imaging method that can perform easy and rapid multi
pass detection of antigen/antibody (Ag/Ab) without the requirement of any
labeling, expensive enzymes, pre-immobilization/modification, and post-washing.
Our method detects Ag or Ab presenting in solutions in a quantitative or
qualitative manner by using micro-lens as the sensor to monitor the refractive
index variation of the solutions during the primary stage of Ag-Ab reaction. The
detection can be taken rapidly and finished in two minutes, while requires very
low sample volume (several micron liters) and its detection limit can be as low
as ~pg/mL. The method is also able to provide kinetic and thermodynamic
parameters of Ag-Ab reactions. The detections of ten Ag-Ab systems and two kinds
of clinical samples demonstrated that our method is of high sensitivity,
accuracy, reliability and permitting on-site analysis.
PMID- 27498329
TI - Ultrasensitive, colorimetric detection of microRNAs based on isothermal
exponential amplification reaction-assisted gold nanoparticle amplification.
AB - MicroRNAs (miRNAs) play important roles in a wide range of biological processes,
and their aberrant expressions are linked to a large number of human diseases and
disorders. In this work, we developed a colorimetric method for rapid,
ultrasensitive miRNA detection via isothermal exponential amplification reaction
(EXPAR)-assisted gold nanoparticle (AuNP) amplification. The sensing probe
designed with a tandem phosphorothioate modification in the backbone of the
polyadenines at the 5' terminus was employed to directly assemble onto the
surface of AuNP with high adsorption affinity. The recognition domain at the 3'
terminus of the sensing probe hybridizes with target miRNAs to trigger EXPAR with
exponential signal amplification. With the amplification reaction with the action
of DNA polymerase, the sensing probe gradually detaches from the AuNP, resulting
in the aggregation of bare AuNPs in the high-salt reaction environment due to
lack of DNA protection. The presence of AuNP aggregation is conveniently measured
by UV-vis spectroscopy. Our proposed method could provide a linear detection
range from 50fM to 10nM with a detection limit of ~46fM within 60min, and also
discriminate a single-nucleotide difference between homologous miRNAs.
PMID- 27498330
TI - A cascade amplification approach for visualization of telomerase activity in
living cells.
AB - An intracellular cascade amplification strategy for ultrasensitive "off-on"
imaging of telomerase activity in living cells was designed. The method was based
on fabrication of a dual function module-encapsulated liposome nanoprobe, which
consisted of a telomerase-targeting responder-transmitter DNA complex (HPT)
module and a catalyzed hairpin assembly (CHA) signal amplification module. Upon
transfected into living cells, the released HPT could be specifically recognized
and extended by telomerase, leading to the release of the transmitter DNA. The
transmitter could act as the initiator and catalyzer of CHA amplification,
resulting in the lightening up of the reporter complex. The telomerase activity
could be monitored in situ by the fluorescence signal without the need for
obtaining cell extracts. Because of the recycling use of the transmitter,
multiplied enhancement of signal outputs from one extension event was achieved.
The proposed strategy could be employed for in situ monitoring of the change of
intracellular telomerase activity in response to drugs to detect drug efficacy.
Thus the method has great potential in the study of the molecular mechanisms of
telomerase-related life processes.
PMID- 27498331
TI - Dual-cyclical nucleic acid strand-displacement polymerization based signal
amplification system for highly sensitive determination of p53 gene.
AB - In the present study, we proposed a novel dual-cyclical nucleic acid strand
displacement polymerization (dual-CNDP) based signal amplification system for
highly sensitive determination of tumor suppressor genes. The system primarily
consisted of a signaling hairpin probe (SHP), a label-free hairpin probe (LHP)
and an initiating primer (IP). The presence of target DNA was able to induce one
CNDP through continuous process of ligation, polymerization and nicking, leading
to extensively accumulation of two nicked triggers (NT1 and NT2). Intriguingly,
the NT1 could directly hybridize SHP, while the NT2 could act as the target
analog to induce another CNDP. The resulting dual-CNDP contributed the striking
signal amplification, and only a very weak blank noise existed since the ligation
template of target was not involved. In this case, the target could be detected
in a wide linear range (5 orders of magnitude), and a low detection limit (78 fM)
was obtained, which is superior to most of the existing fluorescent methods.
Moreover, the dual-CNDP sensing system provided a high selectivity towards target
DNA against mismatched target and was successfully applied to analysis of target
gene extracted from cancer cells or in human serum-contained samples, indicating
its great potential for practical applications.
PMID- 27498332
TI - Dual-component gene detection for H7N9 virus - The combination of optical
trapping and bead-based fluorescence assay.
AB - We present a strategy of dual-component gene detection for avian influenza A
virus H7N9 by combining optical trapping and bead-based fluorescence bioassays. A
low-cost 473nm continuous DPSS laser, polystyrene (PS) beads with two different
sizes (3um and 5um in diameter) and streptavidin-modified 605nm quantum dots (SA
QDs) were exploited in this platform. The beads were employed to enrich the
targets using the classic sandwich mode and tagged with the SA-QDs, then the QDs
tagged beads floating in the suspension were directly trapped and excited by the
optical tweezers to give strong and stable fluorescence signal, which was applied
to quantify the targets. The distinctive size information from the image of the
trapped beads enabled the sorting of the different targets. The results show that
tiny laser power 40MUW is applicable for both trapping and fluorescence
excitation of the beads. Moreover, the limits of detection for hemagglutinin7
(H7) gene and neuraminidase 9 (N9) gene are 1.0-2.0pM with good selectivity for
the complex sample, which is two orders of magnitude lower than that of the
conventional method. More importantly, this strategy was successfully used to
identify the subtype of the avian influenza A virus by simultaneous detection of
H7 and N9 gene sequences. The high sensitivity, good selectivity, typing ability
and the low cost of the laser make this strategy a promising method for life
sciences and clinical applications.
PMID- 27498333
TI - Anterior decompression with fusion versus posterior decompression with fusion for
massive cervical ossification of the posterior longitudinal ligament with a >=50%
canal occupying ratio: a multicenter retrospective study.
AB - BACKGROUND CONTEXT: Previous studies have shown that compared with laminoplasty,
anterior decompression with fusion (ADF) is superior for postoperative neurologic
improvement in patients with massive cervical ossification of the posterior
longitudinal ligament (OPLL) with a >=50% canal occupying ratio. However, it is
unknown which method, ADF or posterior decompression with fusion (PDF), is more
effective for the treatment of massive OPLL. PURPOSE: This study aimed to
investigate the surgical outcomes of ADF and PDF for the treatment of massive
OPLL. STUDY DESIGN: A multicenter retrospective case-control study was carried
out. PATIENT SAMPLE: A total of 61 OPLL patients with a >=50% canal occupying
ratio were included in this study. The mean age of the patients was 60.9 years
(49 males and 12 females); 39 patients (31 males and 8 females, average age 61.1
years) underwent ADF, and 22 patients underwent PDF (18 males and 4 females,
average age 60.6 years). OUTCOME MEASURES: The data collected from both groups
included age, gender, neurologic symptoms evaluated based on the Japanese
Orthopedic Association score, neck pain assessed using the visual analogue scale,
and radiographic parameters, including cervical lordosis and the OPLL canal
occupying ratio. METHODS: Clinical and radiological outcomes were compared
between the ADF and PDF groups with a minimum of 2 years follow-up. RESULTS:
There were no significant differences in the postoperative neurologic recovery
rate between the two groups. However, in patients with kyphotic alignment (C2-C7
angle <0 degrees), the recovery rate was higher in the ADF group. Postoperative
cervical pain was greater in the PDF group. The improvement in cervical alignment
at C2-C7 was greater in the ADF group. The operating time was longer in the ADF
group, whereas the intraoperative blood loss was greater in the PDF group.
Approach-related complications were more frequently observed in the ADF group
than in the PDF group. CONCLUSIONS: The present study demonstrated that the
postoperative recovery rate was similar in the ADF and PDF group. In patients
with massive OPLL with kyphotic alignment, neurologic recovery rate in the ADF
was superior to that in the PDF (in situ fusion). Additionally, postoperative
neck pain was less severe in the ADF group. However, the occurrence of
perioperative complications was more common in the ADF group.
PMID- 27498334
TI - Comparison of fusion rate and clinical results between CaO-SiO2-P2O5-B2O3
bioactive glass ceramics spacer with titanium cages in posterior lumbar interbody
fusion.
AB - BACKGROUND CONTEXT: The CaO-SiO2-P2O5-B2O3 glass ceramics spacer generates
chemical bonding to adjacent bones with high mechanical stability to produce a
union with the end plate, and ultimately stability. PURPOSE: The authors aimed to
compare the clinical efficacy and safety of CaO-SiO2-P2O5-B2O3 glass ceramics
with a titanium cage that is widely used for posterior lumbar interbody fusion
(PLIF) surgery in the clinical field. STUDY DESIGN/SETTING: This is a
prospective, stratified randomized, multicenter, single-blinded, comparator
controlled non-inferiority trial. PATIENT SAMPLE: The present study was conducted
in four hospitals and enrolled a total of 86 patients between 30 and 80 years of
age who required one-level PLIF due to severe spinal stenosis, spondylolisthesis,
or huge disc herniation. OUTCOME MEASURES: The Oswestry Disability Index (ODI),
Short Form-36 Health Survey (SF-36), and pain visual analog scale (VAS) were
assessed before surgery and at 3, 6, and 12 months after surgery. The spinal
fusion rate was assessed at 6 and 12 months after surgery. METHODS: The spinal
fusion rate and the area of fusion, subsidence of each CaO-SiO2-P2O5-B2O3 glass
ceramics and titanium cage, and the extent of osteolysis were evaluated using a
dynamic plain radiography and a three-dimensional computed tomography at 12
months after surgery. The present study was supported by BioAlpha, and some
authors (JHL, C-KL, and B-SC) have stock ownership (<10,000 US dollars). RESULTS:
From the plain radiography results, the 6-month fusion rates for the bioactive
glass ceramics group and the titanium group were 89.7% and 91.4%, respectively.
In addition, the 12-month fusion rates based on CT scan were 89.7% and 91.2%,
respectively, showing no significant difference. However, the bone fusion area
directly attached to the end plate of either bioactive glass ceramics or the
titanium cage was significantly higher in the bioactive glass ceramics group than
in the titanium group. The ODI, SF-36, back pain, and lower limb pain in both
groups significantly improved after surgery, with no significant differences
between the groups. No significant differences between the two groups were
observed in the extent of subsidence and osteolysis. CONCLUSIONS: In lumbar
posterior interbody fusion surgery, CaO-SiO2-P2O5-B2O3 glass ceramics spacer
showed a similar fusion rates and clinical outcomes compared with titanium cage.
PMID- 27498335
TI - Increased sensitivity in the interaction of the dopaminergic/adenosinergic system
at the level of the adenylate cyclase activity in the striatum of the "weaver"
mouse.
AB - The specific antagonistic interaction between dopamine D1 and adenosine A1
receptors (D1/A1), as well as between dopamine D2 and adenosine A2a receptors
(D2/A2a) exist not only at the receptor/receptor level, but also at the level of
the secondary messengers. In this study, we examined the possible changes in
these interactions at the level of cAMP formation in membrane preparation from
"weaver" mouse striatum (a genetic model of Parkinson disease), by using specific
agonists of these receptors. We also examined in the striatum of the "weaver"
mouse the interaction between D1 and D2 dopamine receptors. Our results showed
that in the striatum of "weaver" mice: a) the cAMP synthesis induced by D1
receptor activation (SKF 38393), was significantly reduced compared to control
mice, while A1 receptor activation (L-PIA) leaded to a more intense inhibition of
the D1-induced cAMP-formation compared to the controls, b) the cAMP synthesis
which was induced by A2a receptor activation (CGS 21680), was significantly
increased compared to the control mice. The specific D2 receptor agonist
Quinpirole, added in low concentrations, caused a significant reduction of the
A2a-induced cAMP formation, which was not observed in the control mouse.
Furthermore, the D1 receptor induced cAMP synthesis was significantly higher in
control compared to "weaver" striatum, which was more efficiently downregulated
by D2 receptor agonist Quinpirole. These results suggest that the sensitivity to
D1 and A2a receptor agonists is altered and that the interaction between D1/A1
and D2/A2a receptors is enhanced in the striatum of the "weaver" mutation, while
an uncoupling between D1 and D2 receptors was observed. Since the adenylate
cyclase basal activity did not differ between "weaver" and control striatum, the
above-mentioned changes seem to be due to alterations in the function of the
adenosine/dopamine receptors and their coupling to the G-proteins.
PMID- 27498336
TI - Activation of CRHR1 receptors regulates social and depressive-like behaviors and
expression of BDNF and TrkB in mesocorticolimbic regions following global
cerebral ischemia.
AB - Increased HPA axis activation and CRH release characterize the brain's response
to global cerebral ischemia. Recently, CRH via activation of CRH type 1 receptors
(CRHR1) has been shown to regulate Brain Derived Neurotrophic Factor (BDNF)
secretion and emotional behavior. The current study investigates the impact of
CRHR1 blockade on BDNF/TrkB signaling expression in the mesolimbic circuitry, and
social and depressive-like behavior following global ischemia. Adult male Wistar
rats were injected with Antalarmin (2MUg/MUl) or a vehicle 30min prior to 10min
global cerebral ischemia (4VO model) or sham occlusion. The Three Chamber Social
Approach Test (SIT) assessed sociability and preference for social novelty, and
the novelty suppressed feeding test (NSFT), forced swim test (FST), and sucrose
preference test characterized anxiety and depression. Corticosterone levels and
organ (thymus, seminal and adrenal glands) weights were determined as additional
physiological indices of stress. Immunohistochemistry, Western blot and Rt-PCR
were used to assess BDNF and TrkB receptor levels in subregions of the medial
prefrontal cortex (mPFC), nucleus accumbens (NAc) and ventral tegmental area
(VTA) 30days post-ischemia. Our findings indicate reduced BDNF and TrkB protein
and mRNA expression in the mPFC post-ischemia, while heightened levels were found
in the NAc. Ischemia increased immobility in the FST and reduced sucrose
preference and led to reduced latency to feed in the NSFT and heightened
sociability and social novelty preference in the SIT. Antalarmin treatment
normalized post-ischemic biochemical/behavioral changes. Our findings support
lasting effects of CRHR1 activation on brain plasticity markers, likely playing a
role in emotional impairments following cardio- or cerebro-vascular accidents.
PMID- 27498337
TI - Fast dynamic electron paramagnetic resonance (EPR) oxygen imaging using low-rank
tensors.
AB - Hypoxic tumors are resistant to radiotherapy, motivating the development of tools
to image local oxygen concentrations. It is generally believed that stable or
chronic hypoxia is the source of resistance, but more recent work suggests a role
for transient hypoxia. Conventional EPR imaging (EPRI) is capable of imaging
tissue pO2in vivo, with high pO2 resolution and 1mm spatial resolution but low
imaging speed (10min temporal resolution for T1-based pO2 mapping), which makes
it difficult to investigate the oxygen changes, e.g., transient hypoxia. Here we
describe a new imaging method which accelerates dynamic EPR oxygen imaging,
allowing 3D imaging at 2 frames per minute, fast enough to image transient
hypoxia at the "speed limit" of observed pO2 change. The method centers on a low
rank tensor model that decouples the tradeoff between imaging speed, spatial
coverage/resolution, and number of inversion times (pO2 accuracy). We present a
specialized sparse sampling strategy and image reconstruction algorithm for use
with this model. The quality and utility of the method is demonstrated in
simulations and in vivo experiments in tumor bearing mice.
PMID- 27498338
TI - Cantilever detected ferromagnetic resonance in thin Fe50Ni50, Co2FeAl0.5Si0.5 and
Sr2FeMoO6 films using a double modulation technique.
AB - In this work we introduce a new method, which employs commercial piezo
cantilevers, for a ferromagnetic resonance (FMR) detection from thin, nm-size,
films. Our setup has an option to rotate the sample in the magnetic field and it
operates up to the high microwave frequencies of 160GHz. Using our cantilever
based FMR spectrometer we have investigated a set of samples, namely quasi-bulk
and 84nm film Co2FeAl0.5Si0.5 samples, 16nm Fe50Ni50 film and 150nm Sr2FeMoO6
film. Low frequency and room temperature test of our setup using 84nm
Co2FeAl0.5Si0.5 film yielded a result identical to a standard X-Band
spectrometer, namely a single line with quite small linewidth. Our measurements
at low temperatures and high frequencies revealed a quite strong FMR response
detected in all samples. The FMR spectra share common features, such as the
emergence of the second line with an opposite angular dependence, and a drastic
increase of the linewidths with increasing microwave frequency. We believe that
these findings are results of the complicated dynamics of the magnetization at
low temperatures and high frequencies, which we were able to probe using our
cantilever based FMR setup.
PMID- 27498339
TI - Toxicological properties of fenugreek (Trigonella foenum graecum).
AB - Fenugreek (Trigonella foenum graecum), used as traditional medicine and natural
additive food, has been shown to exert significant antiatherogenic, antidiabetic,
antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and
anti-inflammatory effects in several human and animal models. Besides, several
medicinal pharmaceutical and nutraceutical properties, fenugreek have toxic
effects as well. The aim of this review is discuss the cumulative evidence, which
suggests that consumption of fenugreek induced some serious toxicological side
effects. In this review, many teratogenic effects of fenugreek, from congenital
malformations to death, were reported in human, rodent, rabbit, and chick.
Moreover, results obtained in rats, mice and rabbits show a testicular toxicity
and anti-fertility effects in male associated with oxidative stress and DNA
damage, as well as anti-fertility, antiimplantation and abortifacient activity in
females related to saponin compound of fenugreek which suggest that fenugreek is
not recommended for use during pregnancy. Indeed, the consumption of fenugreek
should be avoided for persons having peanut and chickpeas allergy because of
possible cross-reactivity as well as chronic asthma. Accumulating evidence
suggest also that fenugreek may have neurodevelopmental, neurobehavioral and
neuropathological side effects. It is suggested that future studies would be
conducted to identify molecular and cellular mechanisms underlying the fenugreek
toxicological properties.
PMID- 27498340
TI - Human Papillomavirus Awareness in Haiti: Preparing for a National HPV Vaccination
Program.
AB - STUDY OBJECTIVE: Cervical cancer morbidity and mortality are pressing public
health issues that affect women in Haiti. To inform efforts to develop a human
papillomavirus (HPV) vaccination program in Haiti, we sought to understand HPV
awareness and willingness to get HPV vaccination in Haiti. DESIGN, SETTING, AND
PARTICIPANTS: We interviewed a convenience sample of 475 women and men in 2
clinical settings in Port-au-Prince and Leogane, Haiti between April and July
2014. INTERVENTIONS AND MAIN OUTCOME MEASURES: HPV awareness and willingness to
get HPV vaccine for daughters. RESULTS: Few participants (27%, 130/475) had heard
of HPV. Awareness of HPV was higher among respondents with a previous sexually
transmitted infection compared with those without a previous sexually transmitted
infection (odds ratio, 2.38; 95% confidence interval, 1.10-5.13). Adults who had
heard of genital warts were also more likely to be aware of HPV compared with
those who had not (odds ratio, 4.37; 95% confidence interval, 2.59-7.38). Only
10% (24/250) of parents had previously heard of HPV vaccine; however, after
researchers explained the purpose of the vaccine, nearly all (96%, 240/250) said
they would be willing to get HPV vaccine for their daughters if it were
available. CONCLUSION: Despite low awareness of HPV in Haiti, interest in HPV
vaccination was nearly universal in our study of health care-seeking adults. This
high acceptability suggests that HPV vaccination programs instituted in Haiti
would be well received.
PMID- 27498341
TI - Over 100-year sedimentary record of polycyclic aromatic hydrocarbons (PAHs) and
organochlorine compounds (OCs) in the continental shelf of the East China Sea.
AB - Historical records of polycyclic aromatic hydrocarbons (PAHs), organochlorine
pesticides (OCPs) and polychlorinated biphenyls (PCBs) were analyzed in two dated
sediment cores (DH05 and DH11) collected from the continental shelf of the East
China Sea (ECS) to investigate the influence of anthropogenic activities on
marine sediment over the past century. The concentrations and fluxes of 15 PAHs
were in the range of 28.6-96.5 ng g-1 and 7.6-35.2 ng cm-2 yr-1 in DH05 (1920s
2009), 18.8-76.4 ng g-1 and 13.9-30.9 ng cm-2 yr-1 in DH11 (1860s-2009). The
sedimentary records of PAHs in the two cores generally reflected the economic
development and energy consumption change in China. Identification of sources
suggested that PAHs in ECS were predominantly from petrogenic origin and various
combustion sources. A change of source from low- and moderate-temperature
combustion to high-temperature combustion process was observed. Although a
production ban of technical HCH and DDT was imposed in China in 1983, their
sedimentary fluxes display increasing trends or strong rebounds from 1980s to
1990s as recorded in the core profiles. High proportions of DDD + DDE and gamma
HCH suggested those OCPs mainly derived from early residuals. Temporal trends of
PCBs presented relative high levels from 1970s to 1980s and high proportions of
PCB congeners with 3-6 chlorines atoms indicated industrial sources.
PMID- 27498342
TI - Use of soybean meal and papain to partially replace animal protein for culturing
three marine fish species: Fish growth and water quality.
AB - The main aim of this study was to investigate the feasibility of using soybean
meal added with papain to replace half of the fishmeal used in the moist pellets
(49% fishmeal and 45% trash fish) developed by the Hong Kong Agriculture,
Fisheries and Conservation Department (AFCD) for culturing marine fish. Gold
lined seabream (Rhabdosargus sarba), brown spotted grouper (Epinephelus bleekeri)
and pompano (Trachinotus blochii) were farmed at one of the research stations
(Kat-O) of AFCD, for a period of 340 days. Results indicated that diets
containing papain resulted in better fish growth (reflected by relative weight
gain and feed conversion ratio) than diets without papain. In general, wet weight
gain of fish depends on the amount of papain added in diet rather than the diet
composition. Soybean used in conjunction with papain also contributed to a more
effective growth than fish fed with the moist pellets alone. A laboratory
experiment (using tanks) was conducted to study the effects of the diets on
concentrations of ammonia, nitrite and nitrate in the tank water. Results showed
that concentrations of ammonia and nitrate were significantly lower (p < 0.05)
when the fish were fed with papain-supplemented (with or without soybean meal)
diets. It is envisaged that by using plant protein incorporated with enzymes
could promote better growth of marine fish and lower the adverse impact of trash
fish and fishmeal on water quality of the mariculture zones.
PMID- 27498343
TI - TSLP Down-Regulates S100A7 and beta-Defensin 2 Via the JAK2/STAT3-Dependent
Mechanism.
AB - Elevated T-helper type 2 cytokines in atopic skin, such as IL-4 and IL-13, were
thought to be responsible for an impaired expression of antimicrobial proteins,
which may contribute to the increased susceptibility to skin infections in
patients with atopic dermatitis. In this study, the relationship between thymic
stromal lymphopoietin and antimicrobial proteins and the involved molecular
pathway was defined in normal human epidermal keratinocytes and human skin
equivalent model. Stimulation of normal human epidermal keratinocytes with thymic
stromal lymphopoietin decreased both mRNA and levels of S100A7 and human beta
defensin 2 in a dose-dependent manner, and the regulation was JAK2/STAT3
dependent. Thymic stromal lymphopoietin decreased the antimicrobial protein
expression, even in the presence of IL-17, which is their strong inducer. STAT3
directly regulated the S100A7 and human beta-defensin 2 promoters in normal human
epidermal keratinocytes. Immunohistochemically, lesional atopic skin stained more
intensely with phospho-STAT3 compared with healthy control. Our results show that
up-regulated thymic stromal lymphopoietin may contribute to the deficiency of
antimicrobial proteins in atopic dermatitis, including S100A7 and human beta
defensin 2, by a JAK2/STAT3-dependent mechanism and that STAT3/Sin3a might
directly control the transcriptional activity of the antimicrobial protein
promoters in normal human epidermal keratinocytes. Taken together, a key role of
the JAK2/STAT3/Sin3a signaling pathway in thymic stromal lymphopoietin-mediated
immune response in normal human epidermal keratinocytes might give us clues to
understanding the pathological signal transductions in atopic dermatitis.
PMID- 27498344
TI - A Bifunctional Approach of Immunostimulation and uPAR Inhibition Shows Potent
Antitumor Activity in Melanoma.
AB - Significant advancements of mutation-based targeted therapy and immune checkpoint
blockade have been achieved in melanoma. Nevertheless, acquired resistance and
nonresponders to therapy require different strategies. An innovative approach is
presented here that is based on the combination of innate immune system
activation and simultaneous targeting of the oncogene urokinase-type plasminogen
activator receptor (uPAR). We generated two triphosphate-conjugated siRNAs
targeting uPAR (ppp-uPAR) by in vitro transcription. Specific uPAR knockdown and
simultaneous activation of the retinoic acid-inducible gene 1 (RIG-I) was shown
in different human melanoma cells, fibroblasts, and melanocytes. The compounds
induced massive apoptosis in melanoma cells, whereas fibroblasts and melanocytes
were less sensitive. The effects were less pronounced when the IFN receptor was
blocked. Treatment with ppp-uPAR led to accumulation of p53 and induction of RIG
I-dependent proapoptotic signaling. The apoptotic effects induced by ppp-uPAR
were maintained in melanoma cell lines that had acquired double resistance to B
RAF and MEK/extracellular signal-regulated kinase inhibition. Systemic
intraperitoneal application of ppp-uPAR in nude mice significantly reduced growth
of human melanoma xenografts and elicited a systemic innate immune response with
increased serum cytokine levels. Our data suggest that ppp-uPAR represents a
therapeutically attractive compound that may help overcome the strong therapy
resistance of melanoma.
PMID- 27498345
TI - Targeted Exon Skipping Restores Type VII Collagen Expression and Anchoring Fibril
Formation in an In Vivo RDEB Model.
AB - Dystrophic epidermolysis bullosa is a group of orphan genetic skin diseases
dominantly or recessively inherited, caused by mutations in COL7A1 encoding type
VII collagen, which forms anchoring fibrils. Individuals with recessive
dystrophic epidermolysis bullosa develop severe skin and mucosal blistering after
mild trauma. The exon skipping strategy consists of modulating splicing of a pre
mRNA to induce skipping of a mutated exon. We have targeted COL7A1 exons 73 and
80, which carry recurrent mutations and whose excision preserves the open reading
frame. We first showed the dispensability of these exons for type VII collagen
function in vivo. We then showed that transfection of primary recessive
dystrophic epidermolysis bullosa keratinocytes and fibroblasts carrying null
mutations in exon 73 and/or 80, with 2'-O-methyl antisense oligoribonucleotides,
led to efficient ex vivo skipping of these exons (50-95%) and resulted in a
significant level (up to 36%) of type VII collagen re-expression. Finally, one or
two subcutaneous injections of antisense oligoribonucleotides at doses ranging
from 400 MUg up to 1 mg restored type VII collagen expression and anchoring
fibril formation in vivo in a xenograft model of recessive dystrophic
epidermolysis bullosa skin equivalent. This work provides a proof of principle
for the treatment of patients with recessive dystrophic epidermolysis bullosa by
exon skipping using subcutaneous administration of antisense
oligoribonucleotides.
PMID- 27498346
TI - Adenosine A2A and A2B Receptors Differentially Modulate Keratinocyte
Proliferation: Possible Deregulation in Psoriatic Epidermis.
AB - Adenosine is a potent regulator of inflammation and immunity, but the role of
adenosine receptors in keratinocytes remains controversial. We determined that in
addition to A2B receptors, human epidermal keratinocytes also express A2A
receptors, although to a lower extent. Through the use of selective adenosine
receptor agonists and antagonists, we showed that physiological concentrations of
adenosine activate A2B receptors in normal human keratinocytes, inducing cell
cycle arrest through the increase of intracellular calcium but not through cAMP
signaling. In contrast, the selective activation of A2A receptors by CGS-21680
induces keratinocyte proliferation via p38-mitogen-activated protein kinase
activation. Adenosine and selective A2A and A2B agonists presented anti
inflammatory profiles independent of adenosine receptors but mediated by membrane
phosphatase activation. Finally, keratinocyte exposure to diverse inflammatory
cytokines altered adenosine receptor expression by reducing A2B and increasing
A2A, a pattern also observed in psoriatic epidermis. Because increased epidermal
turnover and inflammatory response are characteristics of psoriatic disease,
further studies are needed to assess the role and consequences of the altered
adenosine receptor expression in lesional and nonlesional psoriatic
keratinocytes.
PMID- 27498347
TI - From mobility to crosstalk. A model of intracellular miRNAs motion may explain
the RNAs interaction mechanism on the basis of target subcellular localization.
AB - MicroRNAs (miRNAs), 22 nucleotides long molecules with the function to reduce
gene expression by inhibiting mRNA translation through partial complementary to
one or more messenger RNA (mRNA) molecules. A single miRNA can reduce the
expression levels of hundreds of genes and one mRNA can be a target for many
miRNAs. Despite the study models used so far, miRNAs and mRNAs cannot be seen as
acting in an isolated manner or even "in pairs". They most likely exert their
complex actions through numerous overlapping interrelations. One of the models
depicting interdependence of intracytoplasmic RNAs is the crosstalk model. It is
based on a competition between several target mRNAs which are regulated by the
same miRNA. In this paper, we will discuss the mobility mechanism of miRNAs,
recently suggested by data from "single particle tracking" experiments. These
data suggests that miRNA intracellular mobility may be of "intermittent active
transport"(IAT) type. IAT is a mobility model composed by alternation of active
transport (AT) and Brownian motion (BM). Based on a mathematical model, we
concluded that, AT phase may explain the efficiency in reaching far targets and
the BM phase may explain the competition. Furthermore, we suggest that the
interaction between miRNAs and their targets depends on the concentration of the
molecules, the affinity between the molecules and also on the intracellular
localization of the molecules. Hence, the probability that a miRNA interacts with
its target depends also on the distance to the target and the macromolecular
crowding. Taken together, our data proposes an intracytoplasmic mobility
mechanism for miRNA and shows that this model can partially explain the RNA
crosstalk.
PMID- 27498348
TI - Preparation of a standardised faecal slurry for ex-vivo microbiota studies which
reduces inter-individual donor bias.
AB - BACKGROUND: In-vitro gut fermentation systems provide suitable models for
studying gut microbiota composition and functionality. However, such methods
depend on the availability of donors and the assumption of reproducibility
between microbial communities before experimental treatments commence. The aim of
this study was to develop a frozen standardised inoculum (FSI) which minimizes
inter-individual variation and to determine its stability over time using culture
dependent and culture-independent techniques. RESULTS: A method for the
preparation difference of a FSI is described which involves pooling the faecal
samples, centrifugation and pelleting of the cell biomass and finally
homogenising the cell pellets with phosphate buffer and glycerol. Using this
approach, no significant difference in total anaerobe cell viability was observed
between the fresh standardised inoculum (before freezing) and the 12days post
freezing FSI. Moreover, Quantitative PCR revealed no significant alterations in
the estimated bacterial numbers in the FSI preparations for any of the phyla.
MiSeq sequencing revealed minute differences in the relative abundance at phylum,
family and genus levels between the FSI preparations. Differences in the
microbiota denoted as significant were limited between preparations in the
majority of cases to changes in percentage relative abundance of +/-0.5%. The
independently prepared FSIs revealed a high degree of reproducibility in terms of
microbial composition between the three preparations. CONCLUSIONS: This study
provides a method to produce a standardised human faecal inoculum suitable for
freezing. Based on culture-dependent and independent analysis, the method ensures
a degree of reproducibility between preparations by lessening the effect of inter
individual variation among the donors, thereby making the system more suitable
for the accurate interpretation of the effects of experimental treatments.
PMID- 27498350
TI - Why should rheumatologists care about fibroblasts?: Answering questions about
tissue tropism and disease persistence.
PMID- 27498349
TI - Bead-beating artefacts in the Bacteroidetes to Firmicutes ratio of the human
stool metagenome.
AB - We evaluated bead-beating cell-lysis in analysing the human stool metagenome,
since this is a key step. We observed that two different bead-beating instruments
from the same producer gave a three-fold difference in the Bacteroidetes to
Firmicutes ratio. This illustrates that bead-beating can have a major impact on
downstream metagenome analyses.
PMID- 27498351
TI - Drug-induced hyperuricaemia and gout.
AB - Hyperuricaemia is a common clinical condition that can be defined as a serum uric
acid level >6.8 mg/dl (404 umol/l). Gout, a recognized complication of
hyperuricaemia, is the most common inflammatory arthritis in adults. Drug-induced
hyperuricaemia and gout present an emergent and increasingly prevalent problem in
clinical practice. Diuretics are one of the most important causes of secondary
hyperuricaemia. Drugs raise serum uric acid level by an increase of uric acid
reabsorption and/or decrease in uric acid secretion. Several drugs may also
increase uric acid production. In this review, drugs leading to hyperuricaemia
are summarized with regard to their mechanism of action and clinical
significance. Increased awareness of drugs that can induce hyperuricaemia and
gout, and monitoring and prevention are key elements for reducing the morbidity
related to drug-induced hyperuricaemia and gout.
PMID- 27498352
TI - Developing anti-inflammatory therapeutics for patients with osteoarthritis.
AB - OA is the most common joint disorder in the world, but there are no approved
therapeutics to prevent disease progression. Historically, OA has been considered
a wear-and-tear joint disease, and efforts to identify and develop disease
modifying therapeutics have predominantly focused on direct inhibition of
cartilage degeneration. However, there is now increasing evidence that
inflammation is a key mediator of OA joint pathology, and also that the link
between obesity and OA is not solely due to excessive load-bearing, suggesting
therefore that targeting inflammation in OA could be a rewarding therapeutic
strategy. In this review we therefore re-evaluate historical clinical trial data
on anti-inflammatory therapeutics in OA patients, highlight some of the more
promising emerging therapeutic targets and discuss the implications for future
clinical trial design.
PMID- 27498353
TI - Chronic hepatitis E in a patient treated with rituximab and mycophenolate mofetil
for Sjogren's syndrome.
PMID- 27498354
TI - Periostitis in secondary syphilis with prozone phenomenon.
PMID- 27498355
TI - Safety and patient response as indicated by biomarker changes to binding
immunoglobulin protein in the phase I/IIA RAGULA clinical trial in rheumatoid
arthritis.
AB - OBJECTIVES: Binding immunoglobulin protein (BiP) is a human endoplasmic reticulum
resident stress protein. In pre-clinical studies it has anti-inflammatory
properties due to the induction of regulatory cells. This randomized placebo
controlled, dose ascending double blind phase I/IIA trial of BiP in patients with
active RA, who had failed accepted therapies, had the primary objective of
safety. Potential efficacy was measured by DAS28-ESR and changes in biomarkers.
METHODS: Twenty-four patients with active RA who had failed one or more DMARDs
were sequentially assigned to three groups each of eight patients randomly
allocated to receive placebo (two patients) or BiP (six patients), 1, 5 or 15 mg.
Patients received a single i.v. infusion over 1 h and were observed as inpatients
overnight. A 12-week follow-up for clinical, rheumatological and laboratory
assessments for safety, efficacy (DAS28-ESR) and biomarker analysis was
performed. RESULTS: No infusion reactions or serious adverse drug reactions were
noted. Adverse events were evenly distributed between placebo and BiP groups with
no BiP-related toxicities. Haematological, renal and metabolic parameters showed
no drug-related toxicities. Remission was only achieved by patients in the 5 and
15 mg groups, and not patients who received placebo or 1 mg BiP. Good DAS28-ESR
responses were achieved in all treatment groups. The BiP responding patients
showed significantly lower serum concentrations of CRP, 2 weeks post-infusion
compared with pre-infusion levels, and of VEGF and IL-8 from the placebo group.
CONCLUSION: BiP (?15 mg) is safe in patients with active RA. Some patients had
clinical and biological improvements in RA activity. BiP merits further study.
TRIAL REGISTRATION: ISRCTN registry, http://isrctn.com, ISRCTN22288225 and
EudraCT, https://eudract.ema.europa.eu, 2011-005831-19.
PMID- 27498356
TI - Dysfunction of endothelial progenitor cells is associated with the type I IFN
pathway in patients with polymyositis and dermatomyositis.
AB - OBJECTIVE: Alterations in phenotype and function of endothelial progenitor cells
(EPCs) have been associated with poor vascular outcomes and impaired vascular
repair in various conditions. Our hypothesis was that patients with PM and DM
have dysregulation of EPCs driven by type I IFN and IL-18 similar to other
autoimmune diseases. METHODS: Quantification of circulating EPCs was performed by
flow cytometry in patients with PM/DM and matched healthy controls. The ability
of EPCs to differentiate into mature endothelial cells was investigated by light
and fluorescence microscopy quantification in the presence or absence of PM/DM or
control serum, neutralizing antibodies to type I IFN receptor or IL-18. Serum
type I IFN activity was quantified by induction of type I IFN-inducible genes in
HeLa cells. Circulating IL-18 concentrations were assessed by ELISA. RESULTS:
Circulating EPCs were significantly lower in PM/DM patients compared with
controls. PM/DM EPCs displayed a decreased capacity to differentiate into mature
endothelial cells and PM/DM serum significantly inhibited differentiation of
control EPCs. This effect was reversed in the majority of samples with
neutralizing antibodies to IL-18 or to type I IFN receptor or by a combination of
these antibodies. Patients with associated impairments in EPC function had higher
type I IFN serum activity. CONCLUSION: PM/DM is associated with dysregulation of
EPC phenotype and function that may be attributed, at least in part, to aberrant
IL-18 and type I IFN pathways. The implication of these vasculopathic findings
for disease prognosis and complications remains to be determined.
PMID- 27498357
TI - T follicular helper cells, interleukin-21 and systemic lupus erythematosus.
AB - SLE is a chronic systemic autoimmune disease characterized by a breakdown of
tolerance to nuclear antigens and generation of high-affinity pathogenic
autoantibodies. These autoantibodies form, with autoantigens, immune complexes
that are involved in organ and tissue damages. Understanding how the production
of these pathogenic autoantibodies arises is of prime importance. T follicular
helper cells (Tfh) and IL-21 have emerged as central players in this process.
This article reviews the pathogenic role of Tfh cells and IL-21 in SLE.
PMID- 27498358
TI - Toluene downregulates filaggrin expression via the extracellular signal-regulated
kinase and signal transducer and activator of transcription-dependent pathways.
PMID- 27498359
TI - Common peptide epitopes induce cross-reactivity in hypersensitivity pneumonitis
serodiagnosis.
PMID- 27498360
TI - Granting Order-Writing Privileges to Registered Dietitian Nutritionists Can
Decrease Costs in Acute Care Hospitals.
PMID- 27498361
TI - Anti-endotoxin and anti-inflammatory effects of Chinese herbal medicinal alkaloid
ingredients in vivo.
AB - The aim of the research was to investigate the anti-endotoxin and anti
inflammatory effects of sinomenine, fangchinoline, stachydrine, chuanxionggzine,
oxymartrine, and evodiamine alkaloids commonly found in Chinese herbal medicines.
In an endotoxin (LPS) control group, each mouse was challenged with 1 mg LPS/kg
by intraperitoneal (IP) injection. In high-, middle- and low-dose alkaloid
groups, mice were initially challenged with 1 mg LPS/kg by IP injection and, 3 h
later, dosed intramuscularly (IM) with one of the six alkaloids at one of three
levels (1, 5, or 10 mg/kg body weight). In the drug control group, mice were
dosed IM with 10 mg/kg body weight of a given alkaloid; mice in a naive control
group were administered the same volume of normal saline. The results revealed
the six alkaloids could reduce the incidence/severity of LPS- induced toxicities,
e.g., body temperature elevation, weight loss, systemic inflammation, multiple
organ dysfunction. Taken together, the data suggested to us that these alkaloids
might effectively regulate inflammatory responses and have a potential to be used
in anti-endotoxin therapies.
PMID- 27498362
TI - In vivo efficacy of single phage versus phage cocktail in resolving burn wound
infection in BALB/c mice.
AB - Klebsiella pneumoniae is one of the most predominant pathogens associated with
burn wound infections, causing considerable morbidity and mortality. The
indiscriminate usage of antibiotics has led to the development of resistant
strains, which have contributed towards the inefficacy of antibiotics. Phage
therapy is a promising alternative to hinder the progression of pathogenic
bacteria. However, phage bacterial resistance is already well known but the use
of phage cocktails can overcome this drawback. The aim of the study was to
evaluate the therapeutic efficacy of monophage (Kpn1, Kpn2, Kpn3, Kpn4 and Kpn5)
in comparison to phage cocktail in resolving the course of burn wound infection
in mice. Although, animals receiving monophage therapy exhibited efficacy in
resolving the course of infection but phage cocktail was highly effective in
arresting the entire infection process (bacterial load, wound contraction, skin
myeloperoxidase activity, collagen formation and histopathological analysis). In
comparison to untreated control mice, a significant reduction in bacterial load
to 4.32, 4.64, 4.42, 4.11 and 4.27 log CFU/ml in Kpn1, Kpn2, Kpn3 Kpn4 and Kpn5
treated animals was obtained respectively was on peak day (3rd day). However, the
group receiving phage cocktail (group 7) showed maximum reduction in bacterial
load in the skin tissue. The bacterial load was significantly reduced to 3.01 log
CFU/ml on peak day. This accounts for a significant reduction of 6 log cycles (p
< 0.01) as compared to that of untreated control animals where a peak of 8.81 log
CFU/ml was seen followed by steady decrease thereafter. Thus, phage cocktail gave
maximum protection against burn wound infection by K. pneumoniae B5055. Compared
to any single phage, phage cocktail significantly checked the emergence of
resistant mutants. Hence this approach can serve as an effective strategy in
treating Klebsiella mediated burn wound infections in individuals who do not
respond to conventional antibiotic therapy.
PMID- 27498363
TI - Toxic effects of nano-ZnO on marine microalgae Skeletonema costatum: Attention to
the accumulation of intracellular Zn.
AB - To explore toxic mechanisms of nano-ZnO on marine microalgae, algal growth
inhibition test was carried out, and total Zn in the cell and total dissolved Zn
in f/2 medium were determined. It was found that nano-ZnO was more toxic than
bulk-ZnO on marine microalgae Skeletonema costatum. No matter under nano-ZnO or
bulk-ZnO treatment, accumulation of intracellular Zn had a good linear
correlation with growth inhibition ratio (IR). The total Zn content in the cell
of microalgae was the dominant toxic mechanism of ZnO. Intracellular total Zn
could be an indispensable parameter to indicate the toxic effects of nano-ZnO.
Higher intracellular total Zn under nano-ZnO treatment than bulk-ZnO resulted in
more toxicity of nano-ZnO on microalgae. Compared with Zn(2+) released by nano
ZnO into medium, lipid peroxidation (MDA level) injury, aggregation of nano-ZnO
and transmembrane process of nano-ZnO also contributed to toxicity of nano-ZnO on
Skeletonema costatum. The accumulation of intracellular Zn provides a new insight
into toxic mechanisms of nano-ZnO.
PMID- 27498364
TI - Dynamic modeling of copper bioaccumulation by Mytilus edulis in the presence of
humic acid aggregates.
AB - Copper (Cu) complexation by humic acids (HA) is expected to decrease Cu
bioavailability for aquatic organisms as predicted by metal bioavailability
models, such as the biotic ligand model (BLM). This has been confirmed for non
feeding organisms such as marine invertebrate embryos or microalgae, but for
filter-feeding organisms such as the mussel Mytilus edulis, Cu bioaccumulation
was higher in the presence of HA, suggesting that part of the Cu-HA complexes
were available for uptake. This study shows the dynamic modeling of Cu
accumulation kinetics in the gills and rest of the soft-body of M. edulis in the
absence and presence of HA. Assuming that truly dissolved Cu is taken in the body
via the gills following BLM premises, and including uptake of Cu-HA aggregates
via the gut into the rest compartment, this two-compartmental model could
successfully explain the observed bioaccumulation data. This modeling approach
gives strong evidence to the hypothesis that Cu-HA aggregates can be ingested by
mussels leading to Cu absorption in the digestive system.
PMID- 27498366
TI - Validating Use of Technology for Cognitive Test Assessment.
PMID- 27498365
TI - Revaccination with Live Attenuated Vaccines Confer Additional Beneficial
Nonspecific Effects on Overall Survival: A Review.
AB - BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV)
and smallpox reduce mortality more than explained by target-disease prevention.
The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in
presence of maternal antibodies. We therefore hypothesised that revaccination in
presence of prior immunity enhances beneficial NSEs. METHODS: Literature search
for studies of revaccination and mortality. FINDINGS: In two randomised trials
(RCTs), two doses versus one dose of MV reduced all-cause mortality by 63% (95%
CI: 23-83%) from 9 to 18months of age. In a quasi-experimental study two doses
before and after 9months compared with one dose of MV after 9months of age
reduced mortality by 59% (25-81%). BCG-revaccination significantly enhanced BCG's
effect against overall child mortality in two RCTs. In a natural experiment study
of OPV campaigns over a 13-year-period in Guinea-Bissau, each additional dose of
OPV was associated with a 13% (4-21%) reduction in mortality rate. The beneficial
NSEs of smallpox vaccination for survival increased significantly with the number
of smallpox vaccination scars. INTERPRETATION: Revaccination with live vaccines
led to substantial reductions in overall mortality. These findings challenge
current understanding of vaccines and may explain the beneficial effects of
campaigns with live vaccines.
PMID- 27498367
TI - Potent ameliorating effect of Hypoxia-inducible factor 1alpha (HIF-1alpha)
antagonist YC-1 on combined allergic rhinitis and asthma syndrome (CARAS) in
Rats.
AB - Recent studies have implicated that Hypoxia-inducible factor 1alpha (HIF-1alpha)
plays an integral role in the pathogenesis of allergic rhinitis and asthma. In
the present study, we showed that HIF-1alpha antagonist YC-1, 3-(5-hydroxymethyl
2-furyl)-1-benzylindazole, elicited a potent allergy-ameliorating effect in a rat
model of ovalbumin (OVA)-sensitized combined allergic rhinitis and asthma
syndrome (CARAS). We revealed that YC-1 administration markedly impaired the
total number and percentage of eosinophil in bronchoalveolar lavage fluid (BAL
Fluid) of the rats, suggesting that YC-1 might attenuate lung and nasal mucosal
inflammation in OVA-sensitized rats. Moreover, histological examination found
that OVA-induced pathological alterations were evidently attenuated following YC
1 administration. In addition, immunohistochemistrial analysis indicated that YC
1 treatment decreased the expression of HIF-1alpha in rat lungs and nasal mucosa.
Notably, Nuclear factor kappa B (NF-kappaB) p65 and Peroxisome proliferator
activated receptor alpha (PPARalpha), two important regulators of inflammatory
responses, were also significantly down-regulated following YC-1 administration.
Real-time PCR analysis confirmed that YC-1 impaired the expression of HIF-1alpha,
NF-kappaB and PPARalpha in CARAS model. These findings together indicated that YC
1 exerted remarkable anti-allergic effects through the modulation of inflammatory
pathways, implying that YC-1 may potentially serve as a novel anti-CARAS medicine
in clinical patients.
PMID- 27498368
TI - Characterization of a selective inverse agonist for estrogen related receptor
alpha as a potential agent for breast cancer.
AB - The estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor that
plays a primary role in the regulation of cellular energy homeostasis and
osteogenesis. It is reported that ERRalpha is widely expressed in a range of
tissues and accumulating evidence has supported that the high expression of
ERRalpha correlates with poor prognosis of various human malignancies, including
breast, endometrium, colon, prostate and ovary cancers. Herein is described the
discovery of a novel selective inverse agonist (HSP1604) of ERRalpha, but not of
ERRbeta and ERRgamma, as determined using transient transfection luciferase
reporter assay and a time-resolved fluorescence resonance energy transfer (TR
FRET) co-activator assay. HSP1604 potently inhibits ERRalpha transcriptional
activity with IC50=1.47+/-0.17MUM in cell-based luciferase reporter assay and
also decreases the protein level of ERRalpha and the mRNA levels of its
downstream target genes such as pyruvate dehydrogenase kinase 4 (PDK4), pS2 and
osteopontin. HSP1604 has also suppressed the proliferation of different human
cancer cell lines and the migration of breast cancer cells with high expression
of ERRalpha. Representative in vivo results show that HSP1604 suppresses the
growth of human breast cancer xenograft in nude mice as doses at 30mg/kg or
100mg/kg administered every other day during 28-day period. HSP1604 thus has the
potential both as a new agent to inhibit the growth of tumors and as a chemical
probe of ERRalpha biology.
PMID- 27498369
TI - Neural correlates of envy: Regional homogeneity of resting-state brain activity
predicts dispositional envy.
AB - Envy differs from common negative emotions across cultures. Although previous
studies have explored the neural basis of episodic envy via functional magnetic
resonance imaging (fMRI), little is known about the neural processes associated
with dispositional envy. In the present study, we used regional homogeneity
(ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions
involved in individual differences in dispositional envy, as measured by the
Dispositional Envy Scale (DES). Results showed that ReHo in the inferior/middle
frontal gyrus (IFG/MFG) and dorsomedial prefrontal cortex (DMPFC) positively
predicted dispositional envy. Moreover, of all the personality traits measured by
the Revised NEO Personality Inventory (NEO-PI-R), only neuroticism was
significantly associated with dispositional envy. Furthermore, neuroticism
mediated the underlying association between the ReHo of the IFG/MFG and
dispositional envy. Hence, to the best of our knowledge, this study provides the
first evidence that spontaneous brain activity in multiple regions related to
self-evaluation, social perception, and social emotion contributes to
dispositional envy. In addition, our findings reveal that neuroticism may play an
important role in the cognitive processing of dispositional envy.
PMID- 27498370
TI - A study of the electro-haemodynamic coupling using simultaneously acquired
intracranial EEG and fMRI data in humans.
AB - In current fMRI studies designed to map BOLD changes related to interictal
epileptiform discharges (IED), which are recorded on simultaneous EEG, the
information contained in the morphology and field extent of the EEG events is
exclusively used for their classification. Usually, a BOLD predictor based on IED
onset times alone is constructed, effectively treating all events as identical.
We used intracranial EEG (icEEG)-fMRI data simultaneously recorded in humans to
investigate the effect of including any of the features: amplitude, width
(duration), slope of the rising phase, energy (area under the curve), or spatial
field extent (number of contacts over which the sharp wave was observed) of the
fast wave of the IED (the sharp wave), into the BOLD model, to better understand
the neurophysiological origin of sharp wave-related BOLD changes, in the
immediate vicinity of the recording contacts. Among the features considered, the
width was the only one found to explain a significant amount of additional
variance, suggesting that the amplitude of the BOLD signal depends more on the
duration of the underlying field potential (reflected in the sharp wave width)
than on the degree of neuronal activity synchrony (reflected in the sharp wave
amplitude), and, consequently, that including inter-event variations of the sharp
wave width in the BOLD signal model may increase the sensitivity of forthcoming
EEG-fMRI studies of epileptic activity.
PMID- 27498371
TI - Integrating cross-frequency and within band functional networks in resting-state
MEG: A multi-layer network approach.
AB - Neuronal oscillations exist across a broad frequency spectrum, and are thought to
provide a mechanism of interaction between spatially separated brain regions.
Since ongoing mental activity necessitates the simultaneous formation of multiple
networks, it seems likely that the brain employs interactions within multiple
frequency bands, as well as cross-frequency coupling, to support such networks.
Here, we propose a multi-layer network framework that elucidates this pan
spectral picture of network interactions. Our network consists of multiple layers
(frequency-band specific networks) that influence each other via inter-layer
(cross-frequency) coupling. Applying this model to MEG resting-state data and
using envelope correlations as connectivity metric, we demonstrate strong
dependency between within layer structure and inter-layer coupling, indicating
that networks obtained in different frequency bands do not act as independent
entities. More specifically, our results suggest that frequency band specific
networks are characterised by a common structure seen across all layers,
superimposed by layer specific connectivity, and inter-layer coupling is most
strongly associated with this common mode. Finally, using a biophysical model, we
demonstrate that there are two regimes of multi-layer network behaviour; one in
which different layers are independent and a second in which they operate highly
dependent. Results suggest that the healthy human brain operates at the
transition point between these regimes, allowing for integration and segregation
between layers. Overall, our observations show that a complete picture of global
brain network connectivity requires integration of connectivity patterns across
the full frequency spectrum.
PMID- 27498372
TI - Temporal control of Dickeya dadantii main virulence gene expression by growth
phase-dependent alteration of regulatory nucleoprotein complexes.
AB - In bacteria, important genes are often controlled at the transcriptional level by
several factors, forming a complex and intertwined web of interactions. Yet,
transcriptional regulators are often studied separately and little information is
available concerning their interactions. In this work, we dissect the regulation
of the major virulence gene pelD in D. dadantii by taking into account the
effects of individual binding sites for regulatory proteins FIS and CRP, and the
impact of a newly discovered divergent promoter div. Using a combination of
biochemistry and genetics approaches we provide an unprecedented level of detail
on the multifactorial regulation of bacterial transcription. We show that the
growth phase dependent regulation of pelD is under the control of changing
composition of higher-order nucleoprotein complexes between FIS, CRP, div and
pelD during the growth cycle that allow sequential expression of div and pelD in
the early and late exponential growth phases, respectively. This work highlights
the importance of "orphan" promoters in gene regulation and that the individual
binding sites for a regulator can serve several purposes and have different
effects on transcription, adding a new level of complexity to bacterial
transcriptional regulation.
PMID- 27498373
TI - Renoprotection by remote ischemic conditioning during elective coronary
revascularization: A systematic review and meta-analysis of randomized controlled
trials.
AB - BACKGROUND: Remote ischemic conditioning (RIC) has been recognized an emerging
non-invasive approach for preventing acute kidney injury (AKI) in patients
undergoing either elective coronary artery bypass graft (CABG) surgery or
percutaneous coronary intervention (PCI). On the other hand, accumulating
evidence has indicated the involving role of pre-CABG contrast usage for coronary
angiography in post-surgery AKI risk. Along with the shortening time delay of
CABG after coronary angiography, and the prevalent hybrid coronary
revascularization (HCR), the AKI prevention by RIC has faced challenges following
coronary revascuralization. METHODS: Randomized controlled trials (RCTs) were
searched from Pubmed, EMBase, and Cochrane library (until May 2016). The primary
outcome was postoperative AKI. The second outcomes were included the requirement
for renal replacement therapy (RRT), and in-hospital or 30-day mortality.
RESULTS: Twenty eligible RCTs (CABG, 3357 patients; PCI, 1501 patients) were
selected. RIC significantly halved the incidence of AKI following PCI when
compared with controls [n=1501; odds ratio (OR)=0.51; 95% CI, 0.32 to 0.82;
P=0.006; I(2)=29.6%]. However, RIC did not affect the incidence of AKI following
CABG (n=1850; OR=0.94; 95% CI, 0.73 to 1.19; P=0.586; I(2)=12.4%). The
requirement for RRT and in-hospital mortality was not affected by RIC in CABG
(n=2049, OR=1.04, P=0.87; n=1920, OR=0.89, P=0.7; respectively). CONCLUSIONS: Our
meta-analysis suggests that RIC for preventing AKI following CABG has faced with
challenges in terms of AKI, the requirement for RRT, and mortality. However, RIC
shows a renoprotective benefit for PCI. Hence, our findings may infer the
preserved renal effects of RIC in CABG with preconditioning before the coronary
angiography, or in HCR.
PMID- 27498375
TI - Telephone vs. Web-based prescreening predicts early but not overall physician
response to a mailed survey.
PMID- 27498374
TI - Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic
effects on the heart and other organs: An expert panel position paper.
AB - Levosimendan is a positive inotrope with vasodilating properties (inodilator)
indicated for decompensated heart failure (HF) patients with low cardiac output.
Accumulated evidence supports several pleiotropic effects of levosimendan beyond
inotropy, the heart and decompensated HF. Those effects are not readily explained
by cardiac function enhancement and seem to be related to additional properties
of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones.
Mechanistic and proof-of-concept studies are still required to clarify the
underlying mechanisms involved, while properly designed clinical trials are
warranted to translate preclinical or early-phase clinical data into more robust
clinical evidence. The present position paper, derived by a panel of 35 experts
in the field of cardiology, cardiac anesthesiology, intensive care medicine,
cardiac physiology, and cardiovascular pharmacology from 22 European countries,
compiles the existing evidence on the pleiotropic effects of levosimendan,
identifies potential novel areas of clinical application and defines the
corresponding gaps in evidence and the required research efforts to address those
gaps.
PMID- 27498376
TI - A systematic review of discontinued trials suggested that most reasons for
recruitment failure were preventable.
AB - OBJECTIVE: To collect and classify reported reasons for recruitment failure in
discontinued randomized controlled trials (RCTs) and to assess reporting quality.
METHODS: We systematically searched MEDLINE and EMBASE (2010-2014) and a previous
cohort of RCTs for published RCTs reporting trial discontinuation due to poor
recruitment. Teams of two investigators selected eligible RCTs working
independently and extracted information using standardized forms. We used an
iterative approach to classify reasons for poor recruitment. RESULTS: We included
172 RCTs discontinued due to poor recruitment (including 26 conference abstracts
and 63 industry-funded RCTs). Of those, 131 (76%) reported one or more reasons
for discontinuation due to poor recruitment. We identified 28 different reasons
for recruitment failure; most frequently mentioned were overestimation of
prevalence of eligible participants and prejudiced views of recruiters and
participants on trial interventions. Few RCTs reported relevant details about the
recruitment process such as how eligible participants were identified, the number
of patients assessed for eligibility, and who actually recruited participants.
CONCLUSION: Our classification could serve as a checklist to assist investigators
in the planning of RCTs. Most reasons for recruitment failure seem preventable
with a pilot study that applies the planned informed consent procedure.
PMID- 27498377
TI - Series: Clinical Epidemiology in South Africa. Paper 3: Logic models help make
sense of complexity in systematic reviews and health technology assessments.
AB - OBJECTIVE: To describe the development and application of logic model templates
for systematic reviews and health technology assessments (HTAs) of complex
interventions. STUDY DESIGN AND SETTING: This study demonstrates the development
of a method to conceptualize complexity and make underlying assumptions
transparent. Examples from systematic reviews with specific relevance to Sub
Saharan Africa (SSA) and other low- and middle-income countries (LMICs)
illustrate its usefulness. RESULTS: Two distinct templates are presented: the
system-based logic model, describing the system in which the interaction between
participants, intervention, and context takes place; and the process-orientated
logic model, which displays the processes and causal pathways that lead from the
intervention to multiple outcomes. CONCLUSION: Logic models can help authors of
systematic reviews and HTAs to explicitly address and make sense of complexity,
adding value by achieving a better understanding of the interactions between the
intervention, its implementation, and its multiple outcomes among a given
population and context. They thus have the potential to help build systematic
review capacity-in SSA and other LMICs-at an individual level, by equipping
authors with a tool that facilitates the review process; and at a system-level,
by improving communication between producers and potential users of research
evidence.
PMID- 27498379
TI - Body dysmorphic disorder in different settings: A systematic review and estimated
weighted prevalence.
AB - Our aim was to systematically review the prevalence of body dysmorphic disorder
(BDD) in a variety of settings. Weighted prevalence estimate and 95% confidence
intervals in each study were calculated. The weighted prevalence of BDD in adults
in the community was estimated to be 1.9%; in adolescents 2.2%; in student
populations 3.3%; in adult psychiatric inpatients 7.4%; in adolescent psychiatric
inpatients 7.4%; in adult psychiatric outpatients 5.8%; in general cosmetic
surgery 13.2%; in rhinoplasty surgery 20.1%; in orthognathic surgery 11.2%; in
orthodontics/cosmetic dentistry settings 5.2%; in dermatology outpatients 11.3%;
in cosmetic dermatology outpatients 9.2%; and in acne dermatology clinics 11.1%.
Women outnumbered men in the majority of settings but not in cosmetic or
dermatological settings. BDD is common in some psychiatric and cosmetic settings
but is poorly identified.
PMID- 27498378
TI - Propensity score model overfitting led to inflated variance of estimated odds
ratios.
AB - OBJECTIVE: Simulation studies suggest that the ratio of the number of events to
the number of estimated parameters in a logistic regression model should be not
less than 10 or 20 to 1 to achieve reliable effect estimates. Applications of
propensity score approaches for confounding control in practice, however, do
often not consider these recommendations. STUDY DESIGN AND SETTING: We conducted
extensive Monte Carlo and plasmode simulation studies to investigate the impact
of propensity score model overfitting on the performance in estimating
conditional and marginal odds ratios using different established propensity score
inference approaches. We assessed estimate accuracy and precision as well as
associated type I error and type II error rates in testing the null hypothesis of
no exposure effect. RESULTS: For all inference approaches considered, our
simulation study revealed considerably inflated standard errors of effect
estimates when using overfitted propensity score models. Overfitting did not
considerably affect type I error rates for most inference approaches. However,
because of residual confounding, estimation performance and type I error
probabilities were unsatisfactory when using propensity score quintile
adjustment. CONCLUSION: Overfitting of propensity score models should be avoided
to obtain reliable estimates of treatment or exposure effects in individual
studies.
PMID- 27498380
TI - Nitrogen loss factors of nitrogen trace gas emissions and leaching from excreta
patches in grassland ecosystems: A summary of available data.
AB - Patches of excreta voided by grazing animals are nitrogen (N) transformation
hotspots in grassland ecosystems and an important source of N trace gas emissions
and leaching. Previous studies have focused on individual N losses from excreta,
but no quantitative analysis has been performed on all the N losses via N trace
gas emissions and leaching. To better understand the fate of N in excreta
patches, we summarized 418, 15, 65, 22, 54, 11, and 81 measurements of nitrous
oxide (N2O), nitric oxide (NO), ammonia (NH3), and ammonium (NH4+) leaching,
nitrate (NO3-) leaching, dissolved organic nitrogen (DON) leaching, and
aboveground plant N uptake, respectively. The results based on field studies
indicated that the average fractions of N lost via N2O were 0.28%, 0.76%, 0.08%,
and 0.35% for cattle dung, cattle urine, sheep dung, and sheep urine,
respectively. Only 0.01-0.12% of excreta N was lost via NO, whereas 1.69-12.7%, 0
4.58%, 16.4-24.6%, and 1.43-5.91% were lost by NH3 and NH4+, NO3-, and DON
leaching, respectively. Aboveground plant parts assimilated 10.4-31.4% of the
excreta N. The N lost via N2O from urine patches decreased as NH3 losses
increased, and greater NO3- leaching occurred with lower plant N uptake. The
combined N2O emission factors for dung and urine from cattle and sheep were 0.59%
and 0.26%, respectively. Each N loss factor was much higher in urine patches than
in dung patches, irrespective of animal type. This study provides general
estimates of N losses and plant N uptake from excreta patches on grazed grassland
based on currently available field data. More field studies are needed in the
future with longer measurement periods from a wide range of climate zones to
refine these N loss factors.
PMID- 27498381
TI - Life-history strategies constrain invertebrate community tolerance to multiple
stressors: A case study in the Ebro basin.
AB - CONTEXT: Multiple stressors constitute a serious threat to aquatic ecosystems,
particularly in the Mediterranean region where water scarcity is likely to
interact with other anthropogenic stressors. Biological traits potentially allow
the unravelling of the effects of multiple stressors. However, thus far, trait
based approaches have failed to fully deliver on their promise and still lack
strong predictive power when multiple stressors are present. GOAL: We aimed to
quantify specific community tolerances against six anthropogenic stressors and
investigate the responses of the underlying macroinvertebrate biological traits
and their combinations. METHODS: We built and calibrated boosted regression tree
models to predict community tolerances using multiple biological traits with a
priori hypotheses regarding their individual responses to specific stressors. We
analysed the combinations of traits underlying community tolerance and the effect
of trait association on this tolerance. RESULTS: Our results validated the
following three hypotheses: (i) the community tolerance models efficiently and
robustly related trait combinations to stressor intensities and, to a lesser
extent, to stressors related to the presence of dams and insecticides; (ii) the
effects of traits on community tolerance not only depended on trait identity but
also on the trait associations emerging at the community level from the co
occurrence of different traits in species; and (iii) the community tolerances and
the underlying trait combinations were specific to the different stressors.
CONCLUSION: This study takes a further step towards predictive tools in community
ecology that consider combinations and associations of traits as the basis of
stressor tolerance. Additionally, the community tolerance concept has potential
application to help stream managers in the decision process regarding management
options.
PMID- 27498382
TI - Impact of sediment particle size on biotransformation of 17beta-estradiol and
17beta-trenbolone.
AB - Soil/sediment particle size has been reported to influence the sorption and
bioavailability of steroid hormones in the environment. However, the impact of
particle size on biotransformation has not been well elucidated. The present
study investigated the dissipation of 17beta-estradiol and 17beta-trenbolone and
the formation and degradation of the subsequent transformation products in
different size fractions of a sandy and a silt loam sediment. The results showed
that the decay of 17beta-estradiol and 17beta-trenbolone associated with fine
particles followed a biphasic pattern with more rapid decay in the initial phase
followed by a second phase with slower decay of the residues compared to their
decay rates in the sand fraction. Estrone and trendione were detected as a
primary biotransformation product for 17beta-estradiol and 17beta-trenbolone,
respectively. The parent-to-product conversion ratios and the degradation rates
of estrone and trendione varied among different size fractions, but no consistent
correlation was observed between decay rates and sediment particle size. Estrone
and trendione decayed in the whole sediments at rates not statistically different
from those associated with the fine fractions. These results indicate that fine
particles may play an important role in influencing the persistence of and the
potential risk posed by steroid hormones in the aquatic systems.
PMID- 27498383
TI - Heart transplantation after donor circulatory death in patients bridged to
transplant with implantable left ventricular assist devices.
PMID- 27498385
TI - Distribution of 45S rDNA in Modern Rose Cultivars (Rosa hybrida), Rosa rugosa,
and Their Interspecific Hybrids Revealed by Fluorescence in situ Hybridization.
AB - To elucidate the evolutionary dynamics of the location and number of rDNA loci in
the process of polyploidization in the genus Rosa, we examined 45S rDNA sites in
the chromosomes of 6 modern rose cultivars (R. hybrida), 5 R. rugosa cultivars,
and 20 hybrid progenies by fluorescence in situ hybridization. Variation in the
number of rDNA sites in parents and their interspecific hybrids was detected. As
expected, 4 rDNA sites were observed in the genomes of 4 modern rose cultivars,
while 3 hybridization sites were observed in the 2 others. Two expected rDNA
sites were found in 2 R. rugosa cultivars, while in the other 3 R. rugosa
cultivars 4 sites were present. Among the 20 R. hybrida * R. rugosa offspring, 13
carried the expected number of rDNA sites, and 1 had 6 hybridization sites, which
exceeded the expected number by far. The other 6 offspring had either 2 or 3
hybridization sites, which was less than expected. Differences in the number of
rDNA loci were observed in interspecific offspring, indicating that rDNA loci
exhibit instability after distant hybridization events. Abnormal chromosome
pairing may be the main factor explaining the variation in rDNA sites during
polyploidization.
PMID- 27498384
TI - Cholesterol efflux capacity of high-density lipoprotein correlates with survival
and allograft vasculopathy in cardiac transplant recipients.
AB - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of mortality
after cardiac transplantation. High-density lipoprotein (HDL) cholesterol efflux
capacity (CEC) is inversely associated with coronary artery disease. In 2
independent studies, we tested the hypothesis that reduced CEC is associated with
mortality and disease progression in CAV. METHODS: We tested the relationship
between CEC and survival in a cohort of patients with CAV (n = 35). To determine
whether reduced CEC is associated with CAV progression, we utilized samples from
the Clinical Trials in Organ Transplantation 05 (CTOT05) study to determine the
association between CEC and CAV progression and status at 1 year (n = 81), as
assessed by average change in maximal intimal thickness (MIT) on intravascular
ultrasound. RESULTS: Multivariable Cox proportional hazard models demonstrated
that higher levels of CEC were associated with improved survival (hazard ratio
0.26, 95% confidence interval 0.11 to 0.63) per standard deviation CEC, p =
0.002). Patients who developed CAV had reduced CEC at baseline and 1-year post
transplant. We observed a significant association between pre-transplant CEC and
the average change in MIT, particularly among patients who developed CAV at 1
year (beta = -0.59, p = 0.02, R2 = 0.35). CONCLUSION: Reduced CEC is associated
with disease progression and mortality in CAV patients. These findings suggest
the hypothesis that interventions to increase CEC may be useful in cardiac
transplant patients for prevention or treatment of CAV.
PMID- 27498386
TI - A 10-Gene Yin Yang Expression Ratio Signature for Stage IA and IB Non-Small Cell
Lung Cancer.
AB - INTRODUCTION: Lung cancer is the leading killer cancer worldwide. There is an
urgent need for easy-to-use and robust clinical gene signatures for improved
prognosis and treatment prediction. METHODS: We used a gene expression signature
termed the Yin and Yang mean ratio (YMR), which is based on two groups of genes
with opposing function, to determine lung cancer prognosis. The YMR signature
represents the relative state of an individual tumor on a gene expression
spectrum ranging from malignancy to the normal healthy lung. The genes in the YMR
signature have therefore been determined independently of survival time, which is
different from previous regression models. We then leveraged the cross-platform
utility of the YMR signature to optimize the signature into a smaller set of
genes that validated the robustness of the signature in many independent lung
cancer expression data sets. RESULTS: Four Yin and six Yang genes were optimized
using 741 NSCLC cases from diverse platforms, including microarray and RNA
sequencing. The 10-gene signature demonstrated significant differences in
survival in eight individual independent data sets and a larger combined 1346
patient data set. When multivariate analysis taking into account other common
predictors of survival was used, the 5-year recurrence-free rate of YMR (p = 6.4
* 10-6, HR =1.71 [1.36-2.16]) was secondary only to stage. The YMR signature
significantly separated high- and low-risk patients with stage IA or 1B
adenocarcinoma and squamous cell carcinomas of all stages. The YMR signature can
also predict the benefit of adjuvant chemotherapy in high-risk patients with
stage I NSCLC. CONCLUSIONS: The YMR signature has great potential for guiding
clinical management for NSCLC, particularly early-stage disease. The signature
appears more reproducible than older signatures and functions using a variety of
common gene expression platforms.
PMID- 27498387
TI - Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell
Lung Cancer-A Multicenter Retrospective Study.
AB - INTRODUCTION: Alectinib and crizotinib have been approved for the therapy of
NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement. The effect
of alectinib or crizotinib on overall survival (OS) in patients with ALK
rearranged NSCLC remains unknown. METHODS: A multicenter retrospective study was
conducted to compare OS between patients receiving alectinib and crizotinib and
between patients treated with alectinib and those treated sequentially with
crizotinib and then alectinib after crizotinib failure. The time to treatment
failure (TTF), progression-free survival (PFS), and OS were compared. RESULTS:
Sixty-one patients with ALK-rearranged NSCLC were enrolled. Forty-six patients
were treated with anaplastic lymphoma kinase (ALK) inhibitors (31 with
crizotinib, 28 with alectinib, and 13 with both ALK inhibitors). The response
rate was 66.7% for the crizotinib-treated group and 80.8% for the alectinib
treated group. Among all patients, TTF and PFS were significantly prolonged in
the alectinib-treated group compared with in the crizotinib-treated group.
Subgroup analyses revealed significantly prolonged TTF for alectinib compared
with crizotinib therapy in the ALK inhibitor-naive population. OS was
significantly longer in the alectinib-treated group than in the crizotinib
treated group. The TTF and OS of patients treated sequentially with crizotinib
and then with alectinib after crizotinib failure tended to be longer than those
of patients treated with alectinib alone. CONCLUSIONS: Therapy with alectinib
alone was significantly superior to therapy with crizotinib alone in terms of
TTF, PFS, and OS, and sequential therapy with crizotinib and alectinib after
crizotinib failure tended to provide a better OS benefit than did therapy with
alectinib alone in patients with ALK-positive NSCLC. However, large-scale
prospective studies are needed to confirm these observations.
PMID- 27498388
TI - Population differentiation and genetic diversity of Trichophyton rubrum as
revealed by highly discriminatory microsatellites.
AB - Little is known regarding the population information of Trichophyton rubrum due
to a lack of strains with clear sampling information and molecular markers with
high discriminatory power. In the present study, we developed a set of
microsatellite markers that have a cumulative discriminatory power was 0.993.
Using these microsatellites loci, 243 strains T. rubrum that had clear sampling
information were analysed. Three genetic diversity indices (Shannon's Information
Index, Nei's unbiased gene diversity and allelic richness) were shown to be
related to the human population size of the sampling city rather than mean annual
temperature or humidity. Population structure analyses revealed that T. rubrum
can be separated into two clusters. AMOVA results indicated that genetic
variation was more significant between these two clusters than among geographical
populations. Our work is the first to reveal population information of T. rubrum
using highly discriminatory molecular markers, and suggest that T. rubrum
populations in cities with larger population size might have better adaptability
due to higher genetic diversity under selective pressures (such as antifungal
agents).
PMID- 27498389
TI - The Fate of Revision Total Knee Arthroplasty With Preoperative Abnormalities in
Either Sedimentation Rate or C-Reactive Protein.
AB - BACKGROUND: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are
important markers in the evaluation and treatment of painful total knee
arthroplasty (TKA). Elevation of both markers usually occurs with infected TKAs
while a normal ESR and CRP usually point to aseptic causes for failure. The
purpose of this study is to compare (1) rate of revision, (2) infection, and (3)
reason for reoperation in a group of patients undergoing revision TKA with a
single abnormality in either ESR or CRP in an otherwise negative conventional
infection work-up compared to patients with normal preoperative ESR and CRP.
METHODS: We retrospectively reviewed 791 consecutive revision TKAs performed at
our institution between years 2004 and 2011. Following exclusion for infection,
periprosthetic fracture, prior revision TKA, positive cultures, incomplete
records, and patients with less than 24-month follow-up, a total of 228 aseptic
revisions (89 knees with 1 abnormal serologic marker) were available for final
analysis. No patients met the current established criteria for infection. All
knees underwent revision TKA using antibiotic-impregnated cement. The 2 groups
were compared in terms of overall survivorship, infection rate, and rate and
causes of subsequent aseptic revision. RESULTS: The average follow-up was 60
months (24-110). There were no significant differences between the 2 groups in
terms of age, sex, American Society of Anesthesiologists class, and Charlson
comorbidity index. A preoperative abnormality of either ESR or CRP significantly
increased the risk for reoperation for all reasons (odds ratio [OR], 3.2; P =
.0028), infection (OR, 4.0; P = .034), and revision for aseptic loosening (OR,
3.69; P = .044). There were no differences in reoperations for any other reason.
The average time to revision in the study group was 28.3 months compared to 40.0
months in the control group (P = .213). CONCLUSION: A single abnormality in
either the ESR or CRP increased the likelihood of both infection and reoperation
following revision TKA. Conventional methods and criteria for infection detection
may not be sufficiently sensitive or specific in these cases. Further work-up
with additional modalities may help increase the confidence of aseptic failure
before revision TKA.
PMID- 27498390
TI - Blood-Sparing Efficacy of Oral Tranexamic Acid in Primary Total Hip Arthroplasty.
AB - BACKGROUND: Tranexamic acid (TXA) has been shown to be effective in reducing
blood loss, hemoglobin drop, and blood transfusion in primary total hip
arthroplasty. Most studies used intravenous form or topical form. This study was
to assess the blood-sparing efficacy and safety of oral TXA in total hip
arthroplasty. METHODS: Patients with primary total hip arthroplasty from 2012 to
2015 were recruited. Trial group with 1 gm of oral TXA 2 hours preoperatively,
and 6 hours and 12 hours postoperatively was compared with the control group
without drug. Outcome measures were intraoperative blood loss, drain output,
observed total blood loss, actual total blood loss, hidden blood loss, hemoglobin
drop, blood transfusion requirement, thromboembolic complications,
cerebrovascular or cardiovascular complications, and mortality. RESULTS: After
exclusion, 108 patients were included-54 in trial group and 54 in control group.
There was no significant difference in the baseline characteristics. The trial
group had significantly higher postoperative hemoglobin (10.3 vs 9.4 g/dL), lower
hemoglobin drop (3.0 vs 4.1 g/dL), lower hidden blood loss (149 vs 354 mL), and
lower actual total blood loss (847 vs 1096 mL). There was no significant
difference in thromboembolic complications or mortality. There was also no
periprosthetic infection or drug allergy. CONCLUSION: Oral TXA is effective in
blood sparing in terms of reduction in hemoglobin drop, hidden blood loss, and
actual total blood loss. It is safe and is an alternative to the intravenous or
topical form.
PMID- 27498391
TI - Identifying potential markers in Breast Cancer subtypes using plasma label-free
proteomics.
AB - : Breast Cancer (BC) is the most common neoplasia among women and has a high
mortality rate worldwide. Over the past several decades, increasing molecular
knowledge of BC has resulted in its stratification into 4 major molecular
subtypes according to hormonal receptor expression. Unfortunately, although the
data accumulated thus far has improved BC prognosis and treatment, there have
been few achievements in its diagnosis. In this study, we applied a Label-free
Nano-LC/MSMS approach to reveal systemic molecular features and possible plasma
markers for BC patients. Compared to healthy control plasma donors, we identified
191, 166, 182, and 186 differentially expressed proteins in the Luminal, Lumina
HER2, HER2, and TN subtypes. In silico analysis demonstrated an overall
downregulation of cellular basal machinery and, more importantly, brought new
focus to the known pathways and signaling molecules in BC that are related to
immune system alterations. Moreover, using western blot analysis, we verified
high levels of BCAS3, IRX1, IRX4 and IRX5 in BC plasma samples, thus highlighting
the potential use of plasma proteomics in investigations into cancer biomarkers.
SIGNIFICANCE: The results of this study provide new insight into Breast Cancer
(BC). We determined the plasma proteomic profile of BC subtypes. Furthermore, we
report that the signaling pathways correlating with late processes in BC already
exhibit plasma alterations in less aggressive subtypes. Additionally, we
validated the high levels of particular proteins in patient samples, which
suggests the use of these proteins as potential disease markers.
PMID- 27498392
TI - An early dysregulation of FAK and MEK/ERK signaling pathways precedes the beta
amyloid deposition in the olfactory bulb of APP/PS1 mouse model of Alzheimer's
disease.
AB - Olfactory dysfunction is an early event of Alzheimer's disease (AD). However, the
mechanisms associated to AD neurodegeneration in olfactory areas are unknown.
Here we used double-transgenic amyloid precursor protein/presenilin 1
(APPswe/PS1dE9) mice and label-free quantitative proteomics to analyze early
pathological effects on the olfactory bulb (OB) during AD progression. Prior to
beta-amyloid plaque formation, 9 modulated proteins were detected on 3-month-old
APP/PS1 mice while 16 differential expressed proteins were detected at 6months,
when beta-amyloid plaques appear, indicating a moderate imbalance in cytoskeletal
rearrangement, and synaptic plasticity in APP/PS1 OBs. Moreover, beta-amyloid
induced an inactivation of focal adhesion kinase (FAK) together with a transient
activation of MEK1/2, leading to inactivation of ERK1/2 in 6-months APP/PS1 OBs.
In contrast, the analysis of human OBs revealed a late activation of FAK in
advanced AD stages, whereas ERK1/2 activation was enhanced across AD staging
respect to controls. This survival potential was accompanied by the inhibition of
the proapototic factor BAD in the OB across AD phenotypes. Our data contribute to
a better understanding of the early molecular mechanisms that are modulated in AD
neurodegeneration, highlighting significant differences in the regulation of
survival pathways between APP/PS1 mice and sporadic human AD. SIGNIFICANCE: Loss
of smell is involved in early stages of Alzheimer's disease (AD), usually
preceding classic disease symptoms. However, the mechanisms governing this
dysfunction are still poorly understood, losing its potential as a useful tool
for clinical diagnosis. Our study characterizes potential AD-associated molecular
changes in APP/PS1 mice olfactory bulb (OB) using MS-quantitative proteomics,
revealing early cytoskeletal disruption and synaptic plasticity impairment.
Moreover, an opposite pattern was found when comparing the activation status of
specific survival pathways between APP/PS1 OBs and OBs derived from sAD subjects
with different neuropathological grading. Our data reflect, in part, the
progressive effect of APP overproduction and Abeta accumulation on the OB
proteome during AD progression.
PMID- 27498393
TI - Quantitative proteomics revealed novel proteins associated with molecular
subtypes of breast cancer.
AB - The early diagnosis and successful treatment of breast cancer (BC) is still a
challenging task due to the diverse origin and functional heterogeneity of cancer
cells. The heterogeneity of BC may likely to explained by molecular BC subtypes,
comprises Luminal-A (LA), Luminal-B (LB), Triple-negative (TN) and HER2-positive
(HP), which are governed by a variety of cancer associated pathways. To identify
protein signatures in different BC subtypes, we performed isobaric tag for
absolute and relative quantitation (iTRAQ) of enriched blood plasma samples of BC
subtypes (N=32) and healthy subjects (N=8). After analyses of data, 58 proteins
were found to be modulated in BC subtypes from healthy subjects (p<0.05) and
among these; Fibronectin (FN1), Alpha-2-macroglobulin (A2M), and Complement
component-4-binding protein-alpha (C4BPA) and Complement factor-B (CFB) were
selected for validation in BC subtypes and healthy subjects in the independent
set of blood plasma (N=100) and tissue samples (N=25). Statistical analysis
showed the significant modulation of FN1 and C4BPA in LB, and A2M in TN patients
in both plasma as well as tissues comparatively control (p<0.05). Further, FN1
and C4BPA in LB subtype revealed a good diagnostic accuracy in plasma level
validation. The receiver operating characteristic (ROC) curve and regression
analysis demonstrated that these proteins with associated criterion of expression
could act as discriminating signatures among BC subtypes with diagnostic and
prognostic relevance. SIGNIFICANCE: The heterogeneity of breast cancer (BC) has
gained many challenges for successful management of BC, thus, the delineating
proteomic alterations BC subtypes may provide great clinical values in
diagnostic, prognostic and therapeutics of BC. The findings from the present
quantitative proteomic study have deciphered the altered proteomic patterns and
their possible molecular interactions in each BC subtype. The study showed a
strong association of FN1, A2M, C4BPA and CFB in molecular subtypes of BC, in
which, C4BPA and A2M demonstrated a potent signature in blood plasma and tissue
samples of LB and TN subtypes in BC patients, respectively. The findings also
revealed the altered level expressions of these selected proteins could classify
BC subtypes through plasma and tissue based expression analysis in patients and
control samples. Hence, these proteins could have clinical importance for the
diagnosis and prognosis purposes among molecular BC subtypes.
PMID- 27498394
TI - Ethical considerations in the de-adoption of ineffective or harmful aspects of
healthcare.
AB - De-adoption refers to the discontinuance of a medical practice or health service
found to be ineffective or harmful following a previous period of adoption. As
growing healthcare budgets threaten to cripple the societies that fund them,
facilitating de-adoption may be integral to sustainable healthcare systems that
provide high-quality care. This article explores ethical issues pertinent to de
adoption including the underpinnings of beneficence, non-maleficence, justice,
and autonomy.
PMID- 27498395
TI - One-step nucleic acid amplification (OSNA) for the detection of sentinel lymph
node metastasis in endometrial cancer.
AB - OBJECTIVE: To evaluate the efficacy of one-step nucleic acid amplification (OSNA)
for the diagnosis of sentinel lymph node (SLN) metastasis compared with
histopathological examination in patients with endometrial carcinoma. METHODS: A
total of 94 SLNs from 34 patients with endometrial carcinoma were enrolled. The
central 1-mm portion of each node was subjected to semi-serial sectioning, sliced
at 200-MUm intervals and examined by hematoxylin and eosin and cytokeratin 19
(CK19) immunohistochemical staining, and the remaining tissue was analysed by
OSNA using CK19 mRNA. The accuracy of the OSNA assay was evaluated based on
histopathological diagnosis. RESULTS: Histologically, 89 SLNs were determined to
be metastasis negative, and the remaining five SLNs were metastasis positive.
Using the breast cancer cutoff value for detecting lymph node metastasis (OSNA
criteria for breast cancer, >250copies/MUl) the sensitivity of the OSNA assay was
100%; specificity was 87.6%; diagnostic accuracy was 88.3%. Discordant results
were recorded for 11 of 94 SLNs. In all 11 cases, a positive result was given by
the OSNA assay but not by histopathological examination. In two SLNs from the
same patient, histopathological examination revealed the presence of benign
epithelial inclusions that were CK19 positive; both SLNs yielded a positive
result in the OSNA assay (true-false positive). All remaining nine histologically
negative/OSNA-positive SLNs were classified as micrometastasis (+) by the OSNA
assay. CONCLUSION: The OSNA assay shows high sensitivity and specificity, which
suggests its utility as a novel tool for the molecular detection of SLN
metastasis in patients with endometrial carcinoma.
PMID- 27498396
TI - Knowledge equals health; why all healthcare professionals should know about
familial hypercholesterolemia.
PMID- 27498397
TI - Impact of statin therapy on plasma adiponectin concentrations: A systematic
review and meta-analysis of 43 randomized controlled trial arms.
AB - BACKGROUND AND AIMS: The effect of statin therapy on plasma adiponectin levels
has not been conclusively studied. Therefore, we aimed to evaluate this effect
through a systematic review and meta-analysis of available randomized controlled
trials (RCTs). METHODS: Quantitative data synthesis was performed using a random
effects model with weighted mean difference (WMD) and 95% confidence interval
(CI) as summary statistics. RESULTS: In 30 studies (43 study arms) with 2953
participants, a significant increase in plasma adiponectin levels was observed
after statin therapy (WMD: 0.57 MUg/mL, 95% CI: 0.18, 0.95, p = 0.004). In
subgroup analysis, atorvastatin, simvastatin, rosuvastatin, pravastatin and
pitavastatin were found to change plasma adiponectin concentrations by 0.70
MUg/mL (95% CI: -0.26, 1.65), 0.50 MUg/mL (95% CI: -0.44, 1.45), -0.70 MUg/mL
(95% CI: -1.08, -0.33), 0.62 MUg/mL (95% CI: -0.12, 1.35), and 0.51 MUg/mL (95%
CI: 0.30, 0.72), respectively. With respect to duration of treatment, there was a
significant increase in the subset of trials lasting >=12 weeks (WMD: 0.88
MUg/mL, 95% CI: 0.19, 1.57, p = 0.012) but not in the subset of <12 weeks of
duration (WMD: 0.18 MUg/mL, 95% CI: -0.23, 0.58, p = 0.390). Random-effects meta
regression suggested a significant association between statin-induced elevation
of plasma adiponectin and changes in plasma low density lipoprotein cholesterol
levels (slope: 0.04; 95% CI: 0.01, 0.06; p = 0.002). CONCLUSIONS: The meta
analysis showed a significant increase in plasma adiponectin levels following
statin therapy. Although statins are known to increase the risk for new onset
diabetes mellitus, our data might suggest that the mechanism for this is unlikely
to be due to a reduction in adiponectin expression.
PMID- 27498398
TI - The relationship between the dietary inflammatory index and risk of total
cardiovascular disease, ischemic heart disease and cerebrovascular disease:
Findings from an Australian population-based prospective cohort study of women.
AB - BACKGROUND AND AIMS: Recently, a pro-inflammatory diet based on a dietary
inflammatory index (DII) has been related to higher CVD risk in general
population, but this has not been investigated among women. METHODS: We
investigated the relationship between DII and risk of total CVD and CVD subgroups
(myocardial infarction, ischemic heart disease, stroke and cerebrovascular
disease) in a prospective cohort of 6972 Australian women aged 50-55 years at
baseline in 2001. We used clinical and procedure information from inpatient
hospital separation registries, information on use of health care services, and
from the causes-of-death registry to ascertain CVD outcomes during 11-year follow
up. The association between baseline DII score and cardiovascular endpoints was
analysed through cox-regression, with correction for demographic and
cardiovascular risk factors. RESULTS: We identified 335 incident cases of CVD and
191 cases of ischaemic heart disease (including 69 myocardial infarctions) and 59
cases of cerebrovascular disease (including 40 cases of stroke). A statistically
significant higher risk of myocardial infarction was observed in analyses using
DII scores as a continuous variable with a hazard ratio of 1.46 (95% confidence
interval 1.12-1.89), but this was attenuated by further adjustment for other
known cardiovascular risk factors. No association was found for total CVD,
ischaemic heart diseases, or cerebrovascular disease. CONCLUSIONS: There was no
statistically significant association between the dietary inflammatory index and
risk of total cardiovascular disease, ischemic heart disease, myocardial
infarction, cerebrovascular disease or stroke in this population of mid-aged
Australian women. Associations were not different for postmenopausal women.
PMID- 27498399
TI - Vestibular-dependent inter-stimulus interval effects on sound evoked potentials
of central origin.
AB - Todd et al. (2014ab) have recently demonstrated the presence of vestibular
dependent contributions to auditory evoked potentials (AEPs) when passing through
the vestibular threshold as determined by vestibular evoked myogenic potentials
(VEMPs), including a particular deflection labeled as an N42/P52 prior to the
long-latency AEPs N1 and P2. In this paper we report the results of an experiment
to determine the effect of inter-stimulus interval (ISI) and regularity on
potentials recorded above and below VEMP threshold. Five healthy, right-handed
subjects were recruited and evoked potentials were recorded to binaurally
presented sound stimulation, above and below vestibular threshold, at seven
stimulus rates with ISIs of 212, 300, 424, 600, 848, 1200 and 1696 ms. The inner
five intervals, i.e. 300, 424, 600, 848, 1200 ms, were presented twice in both
regular and irregular conditions. ANOVA on the global field power (GFP) were
conducted for each of four waves, N42, P52, N1 and P2 with factors of intensity,
ISI and regularity. Both N42 and P52 waves showed significant ANOVA effects of
intensity but no other main effects or interactions. In contrast both N1 and P2
showed additional effects of ISI, as well as intensity, and evidence of non
linear interactions between ISI and intensity. A source analysis was carried out
consistent with prior work suggesting that when above vestibular threshold, in
addition to bilateral superior temporal cortex, ocular, cerebellar and cingulate
sources are recruited. Further statistical analysis of the source currents
indicated that the origin of the interactions with intensity may be the ISI
sensitivity of the vestibular-dependent sources. This in turn may reflect a
specific vestibular preference for stimulus rates associated with locomotion,
i.e. rates close to 2 Hz, or ISIs close to 500 ms, where saccular afferents show
increased gain and the corresponding reflexes are most sensitive.
PMID- 27498401
TI - Points of agreement and difference: A rejoinder to Fischer et al.
PMID- 27498400
TI - Frequency discrimination in the common marmoset (Callithrix jacchus).
AB - The common marmoset (Callithrix jacchus) is a highly vocal New World primate
species that has emerged in recent years as a promising model system for studies
of auditory and vocal processing. Our recent studies have examined perceptual
mechanisms related to the pitch of harmonic complex tones in this species.
However, no previous psychoacoustic work has measured marmosets' frequency
discrimination abilities for pure tones across a broad frequency range. Here we
systematically examined frequency difference limens (FDLs), which measure the
minimum discriminable frequency difference between two pure tones, in marmosets
across most of their hearing range. Results show that marmosets' FDLs are
comparable to other New World primates, with lowest values in the frequency range
of ~3.5-14 kHz. This region of lowest FDLs corresponds with the region of lowest
hearing thresholds in this species measured in our previous study and also with
the greatest concentration of spectral energy in the major types of marmoset
vocalizations. These data suggest that frequency discrimination in the common
marmoset may have evolved to match the hearing sensitivity and spectral
characteristics of this species' vocalizations.
PMID- 27498402
TI - Effect of temperature and water activity on growth and aflatoxin production by
Aspergillus flavus and Aspergillus parasiticus on cured meat model systems.
AB - Dry-cured hams may be colonised by aflatoxin-producing Aspergillus flavus and
Aspergillus parasiticus during the ripening process. The objective of this study
was to evaluate the interaction between non-ionic water stress and temperatures
may have on lag phases prior to growth, growth rates and aflatoxin production by
two strains of each A. parasiticus and A. flavus on meat matrices over a period
of 12days. Results showed that A. flavus CBS 573.65 had shorter lag phases than
A. parasiticus CECT 2688, however the growth rates were quite similar. For both
species, no growth occurred at 10 degrees C and all aw tested and optimum growth
happened at 25 degrees C and 0.95 aw. Similar aflatoxin B1 production profiles
between both species were found, however A. flavus produced much higher
concentration of such toxin than A. parasiticus. Both species produced aflatoxins
when the temperature and the aw were >=15 degrees C and >=0.90.
PMID- 27498404
TI - Expanding the view of breast cancer metabolism: Promising molecular targets and
therapeutic opportunities.
AB - The changes in breast cancer cells that contribute to tumor evolution,
heterogeneity, metastasis and ultimately drug resistance are shaped by numerous
genetic changes including alterations in cellular metabolism. These include
intermediary metabolic pathways such as glycolysis, the citric acid cycle
oxidative phosphorylation, amino acid synthesis and lipid metabolism. However,
cancer cells also exhibit key alterations in other metabolic pathways involved in
drug metabolism such as cytochrome P450 enzymes, sulfotransferase and steroid
sulfatases that are involved in the synthesis of estrogens and themselves serve
as drug targets. In this review we bring together these two sides of metabolism,
discuss the evidence underpinning their role in breast cancer development and
bring to light promising therapeutic targets and up and coming pharmacologic
agents.
PMID- 27498405
TI - The vascular adventitia: An endogenous, omnipresent source of stem cells in the
body.
AB - Until a decade ago it was believed that the wall of adult blood vessels
exclusively contains terminally differentiated cell types. A paradigm shift was
unavoidable since studies from different groups convincingly showed the presence
of vascular wall-resident stem and progenitor cells (VW-SCs) which were
identified to particularly reside in the sub-endothelial space and the so-called
adventitial "vasculogenic zone". Data published during the last decade uncloaked
the fact that VW-SCs have the capacity to differentiate into both vascular and
non-vascular cell types. Up to date, little is known about the full capacity of
VW-SCs, the exact composition of their endogenous niche and the mechanisms that
govern their self-renewal, activation and differentiation. The aim of this review
is to provide an overview about the current knowledge on VW-SCs and to highlight
the impact of this endogenous niche on health and disease. In addition, we will
discuss strategies how these adult stem cells could be manipulated in order to
activate and expand them, ideally within their niche at sites of tissue damage
and subsequently differentiate them into a desired cell type, e.g. an endothelial
cell, a macrophage or a muscle cell. This would pave the way towards new
pharmacological strategies for endogenous tissue repair and regeneration.
PMID- 27498406
TI - Training motor responses to food: A novel treatment for obesity targeting
implicit processes.
AB - The present review first summarizes results from prospective brain imaging
studies focused on identifying neural vulnerability factors that predict
excessive weight gain. Next, findings from cognitive psychology experiments
evaluating various interventions involving food response inhibition training or
food response facilitation training are reviewed that appear to target these
neural vulnerability factors and that have produced encouraging weight loss
effects. Findings from both of these reviewed research fields suggest that
interventions that reduce reward and attention region responses to high calorie
food cues and increase inhibitory region responses to high calorie food cues
could prove useful in the treatment of obesity. Based on this review, a new
conceptual model is presented to describe how different cognitive training
procedures may contribute to modifying eating behavior and important directions
for future research are offered. It is concluded that there is a need for
evaluating the effectiveness of more intensive food response training
interventions and testing whether adding such training to extant weight loss
interventions increases their efficacy.
PMID- 27498407
TI - Expanding specificity of class I restricted CD8+ T cells for viral epitopes
following multiple inoculations of swine with a human adenovirus vectored foot
and-mouth disease virus (FMDV) vaccine.
AB - The immune response to the highly acute foot-and-mouth disease virus (FMDV) is
routinely reported as a measure of serum antibody. However, a critical effector
function of immune responses combating viral infection of mammals is the
cytotoxic T lymphocyte (CTL) response mediated by virus specific CD8 expressing T
cells. This immune mechanism arrests viral spread by killing virus infected cells
before new, mature virus can develop. We have previously shown that infection of
swine by FMDV results in a measurable CTL response and have correlated CTL
killing of virus-infected cells with specific class I major histocompatibility
complex (MHC) tetramer staining. We also showed that a modified replication
defective human adenovirus 5 vector expressing the FMDV structural proteins (Ad5
FMDV-T vaccine) targets the induction of a CD8+ CTL response with a minimal
humoral response. In this report, we show that the specificity of the CD8+ T cell
response to Ad5-FMDV-T varies between cohorts of genetically identical animals.
Further, we demonstrate epitope specificity of CD8+ T cells expands following
multiple immunizations with this vaccine.
PMID- 27498408
TI - Characterization and functional studies of fowl adenovirus 9 dUTPase.
AB - Deoxyuridine 5'-triphosphate pyrophosphatase (dUTPase), a ubiquitous enzyme that
catalyzes the hydrolysis of dUTP to dUMP and found in many viruses, has yet to be
identified in fowl adenovirus 9 (FAdV-9). By a multiple alignment of dUTPase
amino acid sequences, FAdV-9 ORF1 contained the five conserved motifs that define
the protein family, and encoded a functional dUTPase. Moreover, transcription and
protein expression patterns were characterized, indicating that dUTPase was
transcribed from 2h post-infection (h.p.i.) and translated from 6h.p.i., and both
continued to the late phase of virus infection. An HA-tagged dUTPase recombinant
virus was generated, and dUTPase was found to be localized in both the cytoplasm
and nucleus in chicken hepatoma cells (CH-SAH). A dUTPase knockout virus was
generated and compared with the wild-type virus, showing that dUTPase upregulated
the expression of type I interferons, but was not required for viral DNA or virus
replication in CH-SAH cells.
PMID- 27498411
TI - Fusion of sparse representation and dictionary matching for identification of
humans in uncontrolled environment.
AB - Biomechanics based human identification is a major area of research. Biomechanics
based approaches depend on accurately recognizing humans using body movements,
the accuracy of these approaches is enhanced by incorporating the knee-hip angle
to angle relationships. Current biomechanics based models are developed by
considering the biomechanics of human walking and running. In biomechanics the
joint angle characteristics, also known as gait features play a vital role in
identification of humans. In general, identification of humans can be broadly
classified into two approaches: biomechanics based approach, also known as Gait
Recognition and biometric based Composite Sketch Matching. Gait recognition is a
biomechanics based approach which uses gait traits for person authentication, it
discriminates people by the way they walk. Gait recognition uses shape and motion
information of a person and identifies the individual; this information is
generally acquired from an image sequence. The efficiency of gait recognition is
mainly affected by covariates such as observation view, walking speed, clothing,
and belongings. Biometric based approach for human identification is usually done
by composite sketch matching. Composite sketches are sketches generated using a
computer. This obviates the need of using a skilled sketch artist; these sketches
can be easily drawn by eyewitness using face design system software in a very
short time period. This doesn't require any prior specialized software training
but identifying humans using only composite sketches is still a challenging task
owing to the fact that human faces are not always clearly visible from a
distance. Hence drawing a composite sketch at all times is not feasible. The key
contribution of this paper is a fusion system developed by combining biomechanics
based gait recognition and biometric based composite sketch matching for
identifying humans in crowded scenes. First various existing biomechanics based
approaches for gait recognitionare developed. Then a novel biomechanics based
gait recognition is developed using Sparse Representation to generate what we
term as "score 1." Further another novel technique for composite sketch matching
is developed using Dictionary Matching to generate what we term as "score 2."
Finally, score level fusion using Dempster Shafer and Proportional Conflict
Distribution Rule Number 5 is performed. The proposed fusion approach is
validated using a database containing biomechanics based gait sequences and
biometric based composite sketches. From our analysis we find that a fusion of
gait recognition and composite sketch matching provides excellent results for
real-time human identification.
PMID- 27498409
TI - The absence of p53 during Human Cytomegalovirus infection leads to decreased UL53
expression, disrupting UL50 localization to the inner nuclear membrane, and
thereby inhibiting capsid nuclear egress.
AB - Our electron microscopy study (Kuan et al., 2016) found HCMV nuclear capsid
egress was significantly reduced in p53 knockout cells (p53KOs), correlating with
inhibited formation of infoldings of the inner nuclear membrane (IINMs).
Molecular examination of these phenomena has found p53KOs expressed UL97 and
phosphorylated lamins, however the lamina failed to remodel. The nuclear egress
complex (NEC) protein UL50 was expressed in almost all cells. UL50 re-localized
to the inner nuclear membrane (INM) in ~90% of wt cells, but only ~35% of p53KOs.
UL53 expression was significantly reduced in p53KOs, and cells lacking UL50
nuclear staining, expressed no UL53. Re-introduction of p53 into p53KOs largely
recovered UL53 positivity and UL50 nuclear re-localization. Nuclear rim located
UL50/53 puncta, which co-localized with the major capsid protein, were largely
absent in p53KOs. We believe these puncta were IINMs. In the absence of p53, UL53
expression was inhibited, disrupting formation of the NEC/IINMs, and reducing
functional virion secretion.
PMID- 27498410
TI - Human Cytomegalovirus nuclear egress and secondary envelopment are negatively
affected in the absence of cellular p53.
AB - Human Cytomegalovirus (HCMV) infection is compromised in cells lacking p53, a
transcription factor that mediates cellular stress responses. In this study we
have investigated compromised functional virion production in cells with p53
knocked out (p53KOs). Infectious center assays found most p53KOs released
functional virions. Analysis of electron micrographs revealed modestly decreased
capsid production in infected p53KOs compared to wt. Substantially fewer p53KOs
displayed HCMV-induced infoldings of the inner nuclear membrane (IINMs). In
p53KOs, fewer capsids were found in IINMs and in the cytoplasm. The deficit in
virus-induced membrane remodeling within the nucleus of p53KOs was mirrored in
the cytoplasm, with a disproportionately smaller number of capsids re-enveloped.
Reintroduction of p53 substantially recovered these deficits. Overall, the
absence of p53 contributed to inhibition of the formation and function of IINMs
and re-envelopment of the reduced number of capsids able to reach the cytoplasm.
PMID- 27498412
TI - Micro- and macro-metastasis in the axillary lymph node: A review.
AB - Pathologists typically examine the sentinel lymph nodes excised from patients
with invasive breast cancer more thoroughly than they have historically those
from axillary lymph node clearance specimens. This, it is thought, increases the
chances of detecting small metastatic foci (i.e. macrometastases (>2 mm),
micrometastases (0.2-2 mm), or isolated tumour cell clusters (<0.2 mm or <200
cancer cells in one section)). However, the clinical significance of these small
metastatic deposits remains unclear. Although an increasing nodal burden is known
to proportionally decrease patient survival, the American College of Surgeons
Oncology Group (ACOSOG) Z0011 trial has, at the least, raised questions as to how
best to manage nodal metastasis in early invasive breast cancer. These issues,
and a brief overview of the biology of metastatic spread are presented in this
review.
PMID- 27498413
TI - Physical stability of R-(+)-Limonene emulsions stabilized by Ulva fasciata algae
polysaccharide.
AB - The physical stability of R-(+)-Limonene emulsions stabilized by Ulva fasciata
polysaccharide (UFP) was investigated in this study. Emulsion physical stability
was evaluated under different polysaccharide concentrations (1%-5%, wt/wt) and pH
values (3.0-11.0). The stability of R-(+)-Limonene emulsions was demonstrated by
droplet size distribution, rheological properties, zeta potential and visual
phase separation. R-(+)-Limonene emulsions displayed monomodal droplet size
distributions, high absolute values of zeta potential and good storage stability
when 3% (wt/wt) UFP was used. The rheological properties and stability of R-(+)
Limonene emulsions appeared to be dependent on polysaccharide concentration. The
emulsion stability was impacted by pH. Higher zeta potential (-52.6mV) and
smaller mean droplet diameter (2.45MUm) were achieved in neutral liquid
environment (pH 7.0). Extreme acidity caused the flocculation of emulsions, which
was manifested as phase separation, while emulsions were quite stable in an
alkaline environment. Through comparing the stabilities of emulsions stabilized
by different emulsifiers (i.e. UFP, GA and Gelatin), the result suggested that
UFP was the best emulsifying agent among them.
PMID- 27498414
TI - Polysaccharides from Pleurotus ostreatus alleviate cognitive impairment in a rat
model of Alzheimer's disease.
AB - This study was conducted to evaluate the effects of polysaccharides extracted
from Pleurotus ostreatus (POP) on d-galactose and AlCl3-induced cognitive
impairments. A behavioral test suggested that POP significantly decreased escape
latency and increased crossing parameters of platform quadrant in a Morris water
maze test. Furthermore, POP decreased error numbers and increased passive
avoidance latency in a step-down test. Biochemical examinations revealed that POP
significantly elevated superoxide dismutase, glutathione peroxidase, and catalase
activities; and reduced malondialdehyde levels and acetylcholinesterase activity.
Moreover, POP could decrease amyloid beta peptide formation and tau
phosphorylation by elevating the expression of protein phosphatase 2A as well as
by reducing the expression of amyloid precursor protein (APP), beta-site APP
clearing enzyme1, and glycogen synthase kinase 3beta. These findings provide
scientific evidence to support the exploitation of POP as a safe and effective
drug to prevent and treat Alzheimer's disease.
PMID- 27498415
TI - S-layer proteins from Lactobacillus sp. inhibit bacterial infection by blockage
of DC-SIGN cell receptor.
AB - Many species of Lactobacillus sp. possess Surface(s) layer proteins in their
envelope. Among other important characteristics S-layer from Lactobacillus
acidophilus binds to the cellular receptor DC-SIGN (Dendritic Cell-Specific
Intercellular adhesion molecule-3-Grabbing Non-integrin; CD209), which is
involved in adhesion and infection of several families of bacteria. In this
report we investigate the activity of new S-layer proteins from the Lactobacillus
family (Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus helveticus
and Lactobacillus kefiri) over the infection of representative microorganisms
important to human health. After the treatment of DC-SIGN expressing cells with
these proteins, we were able to diminish bacterial infection by up to 79% in both
gram negative and mycobacterial models. We discovered that pre-treatment of the
bacteria with S-layers from Lactobacillus acidophilus and Lactobacillus brevis
reduced bacteria viability but also prevent infection by the pathogenic bacteria.
We also proved the importance of the glycosylation of the S-layer from
Lactobacillus kefiri in the binding to the receptor and thus inhibition of
infection. This novel characteristic of the S-layers proteins may contribute to
the already reported pathogen exclusion activity for these Lactobacillus
probiotic strains; and might be also considered as a novel enzymatic
antimicrobial agents to inhibit bacterial infection and entry to host cells.
PMID- 27498416
TI - Novel nanocomposites with selective antibacterial action and low cytotoxic effect
on eukaryotic cells.
AB - In the present study we synthesized lignin-tetra ethoxysilane (TEOS)
nanocomposite and characterized it using UV-spectroscopy, Fourier Transform Infra
red spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Field Emission
Scanning Electron Microscopy (FE-SEM) and Scanning Electron Microscopy (SEM). XRD
spectra and SEM micrographs confirmed a relatively high degree of crystallinity
(peaks located at lower angle, 2theta=12 degrees and 2theta=22.0 degrees ) and
porous nature of nanocomposite. The lignin-TEOS nanocomposites depicted
antibacterial activity against the test microorganisms (Pseudomonas aerugenosa
MTCC 741, Escherichia coli MTCC 739, Bacillus subtilis MTCC 441 and
Staphylococcus aureus MTCC 96) whereas at the same concentration did not show any
significant cytotoxicity against various tissue-specific cancer cell lines such
as breast cancer: MCF-7, MDA-MB-231, MDA-MB-468, BT-549; lung cancer: A-549;
prostate cancer: PC-3, Du-145; as well as primary control cells-Human hepatic
stellate cells (HHSteCs). The present study suggests the plausible translational
role of these nanocomposites as an antimicrobial agent for wound dressings due to
its potent antimicrobial activity with low toxicity to non-target eukaryotic
cells. Nevertheless, these nanocomposites may also be used as packaging materials
due to their antimicrobial activity.
PMID- 27498417
TI - Adsorption and intercalation of low and medium molar mass chitosans on/in the
sodium montmorillonite.
AB - Chitosan-montmorillonite composites can provide hydrophobicity and amino groups
to enhance the performances of montmorillonite in wastewater treatment. In this
paper, low molar mass chitosan (LC) and medium molar mass chitosan (MC) were
selected to intercalate a sodium montmorillonite (Mt). The adsorption isotherm of
LC and MC on the Mt and the pH dependency were measured. Thermo X-ray diffraction
(XRD) and Fourier transform infrared spectroscopy (FTIR) were used to
characterize the chitosan-Mt composites. Results showed that with hydrochloric
acid as the solvent of chitosans, increasing pH from 3 to 5.5 enhanced the
adsorption of both LC and MC on the Mt, and when the equilibrium concentration of
chitosans approached 300mg/L at pH 5.5, the amount of adsorbed chitosan reached
the highest level of 0.203mg/mg for LC and 0.190mg/mg for MC, respectively. When
the Mt was saturated with the chitosan, the amino groups on the chitosan were
bonded with the Mt through electrostatic interaction and there was monolayer of
the chitosan in the interlayer space of Mt, which were confirmed by FTIR spectra
and XRD patterns, respectively.
PMID- 27498418
TI - Fgf23 and parathyroid hormone signaling interact in kidney and bone.
AB - Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, suppressing renal
phosphate reabsorption and vitamin D hormone synthesis in proximal tubules, and
stimulating calcium reabsorption in distal tubules of the kidney. Here, we
analyzed the long term sequelae of deficient Fgf23 signaling on bone and mineral
metabolism in 9-month-old mice lacking both Fgf23 or Klotho and a functioning
vitamin D receptor (VDR). To prevent hypocalcemia in VDR deficient mice, all mice
were kept on a rescue diet enriched with calcium, phosphate, and lactose. VDR
mutants were normocalcemic and normophosphatemic, and had normal tibial bone
mineral density. Relative to VDR mutants, Fgf23/VDR and Klotho/VDR compound
mutants were characterized by hypocalcemia, hyperphosphatemia, and very high
serum parathyroid hormone (PTH). Despite ~10-fold higher serum PTH levels in
compound mutants, urinary excretion of phosphate and calcium as well as
osteoclast numbers in bone remained unchanged relative to VDR mutants. The
increase in plasma cAMP after hPTH(1-34) injection was similar in all genotypes.
However, a 5-day infusion of hPTH(1-34) via osmotic minipumps resulted in reduced
phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in bone
and kidney of Fgf23/VDR and Klotho/VDR compound mutants, relative to VDR and WT
controls. Similarly, the PTH-mediated ERK1/2 phosphorylation was reduced in
primary osteoblasts isolated from Fgf23 and Klotho deficient mice, but was
restored by concomitant treatment with recombinant FGF23. Collectively, our data
indicate that the phosphaturic, calcium-conserving, and bone resorption
stimulating actions of PTH are blunted by Fgf23 or Klotho deficiency. Hence,
FGF23 may be an important modulator of PTH signaling in bone and kidney.
PMID- 27498420
TI - Hypothalamus and thermogenesis: Heating the BAT, browning the WAT.
AB - Brown adipose tissue (BAT) has been also considered as the main thermogenic organ
responsible of maintenance body temperature through heat production. However, a
new type of thermogenic fat has been characterized during the last years, the
beige or brite fat, that is developed from white adipose tissue (WAT) in response
to different stimuli by a process known as browning. The activities of brown and
beige adipocytes ameliorate metabolic disease, including obesity in mice and
correlate with leanness in humans. Many genes and pathways that regulate brown
and beige adipocyte biology have now been identified, providing a variety of
promising therapeutic targets for metabolic disease. The hypothalamus is the main
central place orchestrating the outflow signals that drive the sympathetic nerve
activity to BAT and WAT, controlling heat production and energy homeostasis.
Recent data have revealed new hypothalamic molecular mechanisms, such as
hypothalamic AMP-activated protein kinase (AMPK), that control both thermogenesis
and browning. This review provides an overview of the factors influencing BAT and
WAT thermogenesis, with special focus on the integration of peripheral
information on hypothalamic circuits controlling thermoregulation.
PMID- 27498419
TI - Celecoxib treatment of fibrous dysplasia (FD) in a human FD cell line and FD-like
lesions in mice with protein kinase A (PKA) defects.
AB - Osteochondromyxomas (OMX) in the context of Carney complex (CNC) and fibrous
dysplasia (FD)-like lesions (FDLL) in mice, as well as isolated myxomas in humans
may be caused by inactivation of PRKAR1A, the gene coding for the type 1a
regulatory subunit (R1alpha) of cAMP-dependent protein kinase (PKA). OMXs and
FDLL in mice lacking Prkar1a grow from abnormal proliferation of adult bone
stromal cells (aBSCs). Prkar1a and Prkaca (coding for Calpha) haploinsufficiency
leads to COX2 activation and prostaglandin E2 (PGE2) production that, in turn,
activates proliferation of aBSCs. Celecoxib is a cyclooxygenase-2 (COX2)
inhibitor. We hypothesized that COX-2 inhibition may have an effect in FD and
FDLL. In vitro treatment of a human cell line prepared from a FD patient with
Celecoxib resulted in decreased PGE2 and cell proliferation. Treatment of mice
haploinsufficient for R1alpha and Calpha with 1500 mg/kg Celecoxib led to
decreased PGE2 and proliferation and increased apoptosis, with a corresponding
gene expression profile, resulting in dramatic reduction of tumor growth.
Furthermore, the treatment improved the organization of cortical bone that was
adjacent to the tumor. We conclude that, in vitro and in vivo, Celecoxib had an
inhibitory effect on FD cell proliferation and in mouse FDLL structure,
respectively. We speculate that COX-2 inhibitors offer an attractive alternative
to current treatments for benign tumors such as OMX and FD that, apart from tumor
suppression, may mechanically stabilize affected bones.
PMID- 27498421
TI - Increased prevalence of human cutaneous leishmaniasis in Israel and the
Palestinian Authority caused by the recent emergence of a population of
genetically similar strains of Leishmania tropica.
AB - Twelve unlinked microsatellite markers were used to determine the microsatellite
profiles of 50 newly and 46 previously typed strains of L. tropica from various
Israeli and Palestinian foci. Their microsatellite profiles were compared to
those of 99 previously typed strains of L. tropica from 15 countries. Israeli and
Palestinian strains of L. tropica fell into three different groups, one of which
contained 75 of the 96 Israeli and Palestinian strains. This population separated
from all the others at the first hierarchical level by Bayesian statistics and
formed a distinct monophyletic group on applying genetic distance and allele
frequency analyses. The second cluster contained ten Israeli strains from a
specific focus north of the Sea of Galilee, which were previously shown to differ
from all other strains of L. tropica in their serological, biochemical and
molecular biological parameters. This cluster was closely related to clusters
comprising strains of L. tropica from Africa. Four Israeli and five Palestinian
strains fell into different genetic entities mostly related to strains from Asian
foci of CL. Importation during numerous migrations of humans and, perhaps,
infected reservoir animals in the past and, now, through modern travel is the
most likely explanation for the existence of so many locally encountered genetic
variants of L. tropica in the Israeli-Palestinian region. Geographical and
ecological variation may play a role in expanding the genetic heterogeneity once
given importations had become established in different foci. Currently, one
population is expanding in the area comprising almost all of the Palestinian and
Israeli strains of L. tropica isolated since 1996 and investigated in this study,
which differ clearly from all other strains of whatsoever origin. This population
seems to result from the re-emergence of a previously existing genotype owing to
environmental changes and human activities.
PMID- 27498422
TI - Prediction of cyclic delamination lives of plasma-sprayed hydroxyapatite coating
on Ti-6Al-4V substrates with considering wear and dissolutions.
AB - This study aims at developing the prediction model of cyclic delamination lives
of plasma-sprayed HAp coating on Ti-6Al-4V substrate by considering wear by
interface contacts and dissolution effect by Simulated Body Fluid (SBF).
Delamination of HAp coating can lead to loosening of implants stem and final
failure in vivo. In the fracture mechanism of interfaces between HAp coating with
Ti substrates, only adhesive strength (interracial tensile strength) or fatigue
behavior by longitudinal cracking have been observed. Cyclic delamination
mechanism by considering various loading modes and corrosion effect has not been
revealed yet. The interface delamination rates by cyclic loading were much higher
than those by static loading tests. The result clearly demonstrated that the
interface demalination behaviors are dominated not by maximum stress, but by
stress range. Surface profile measurement and SEM observation also demonstrated
damages by interface contact or third body wear at delamination tips of HAp
coating only in the cases of compressions. The mechanisms of acceleration on the
delaminations are third-body wear or wedge effect by worn particles which
increased mean stress level during cyclic loading. Cyclic loading tests under SBF
also revealed that cyclic delamination lives were shortened probably due to
crevice corrosion at interfaces. Dissolutions at the tips of delaminations were
observed by SEM images under tensile loading condition in SBF. Linearly adding
the effects of wear and dissolutions into Paris law could successfully predict
the delamination lives of HAp coating for various loading ratios in SBF.
PMID- 27498423
TI - Giant panda's tooth enamel: Structure, mechanical behavior and toughening
mechanisms under indentation.
AB - The giant panda's teeth possess remarkable load-bearing capacity and damage
resistance for masticating bamboos. In this study, the hierarchical structure and
mechanical behavior of the giant panda's tooth enamel were investigated under
indentation. The effects of loading orientation and location on mechanical
properties of the enamel were clarified and the evolution of damage in the enamel
under increasing load evaluated. The nature of the damage, both at and beneath
the indentation surfaces, and the underlying toughening mechanisms were explored.
Indentation cracks invariably were seen to propagate along the internal
interfaces, specifically the sheaths between enamel rods, and multiple extrinsic
toughening mechanisms, e.g., crack deflection/twisting and uncracked-ligament
bridging, were active to shield the tips of cracks from the applied stress. The
giant panda's tooth enamel is analogous to human enamel in its mechanical
properties, yet it has superior hardness and Young's modulus but inferior
toughness as compared to the bamboo that pandas primarily feed on, highlighting
the critical roles of the integration of underlying tissues in the entire tooth
and the highly hydrated state of bamboo foods. Our objective is that this study
can aid the understanding of the structure-mechanical property relations in the
tooth enamel of mammals and further provide some insight on the food habits of
the giant pandas.
PMID- 27498424
TI - Characterization and investigation of the deformation behavior of porous
magnesium scaffolds with entangled architectured pore channels.
AB - We report a kind of porous magnesium with entangled architectured pore structure
for potential applications in biomedical implant. The pore size, spatial
structure and Young's modulus of the as-prepared porous Mg are suitable for bone
tissue engineering applications. Particularly, with regard to the load-bearing
conditions, a new analytical model is employed to investigate its structure and
mechanical response under compressive stress based on Gibson-Ashby model. It is
found that there are three types of stress-strain behaviors in the large range of
porosity from 20% to 80%. When the porosity is larger than an upper critical
value, the porous magnesium exhibits densifying behavior with buckling
deformation mechanism. When the porosity is smaller than a lower critical value,
the porous magnesium exhibits shearing behavior with cracking along the maximum
shear stress. Between the two critical porosities, both the buckling deformation
and shearing behavior coexist. The upper critical porosity is experimentally
determined to be 60% for 270MUm pore size and 62% for 400MUm pore size, while the
lower critical porosity is 40% for 270MUm pore size and 42% for 400MUm pore size.
A new analytical model could be used to accurately predict the mechanical
response of the porous magnesium. No matter the calculated critical porosity or
yielding stress in a large range of porosity by using the new model are well
consistent with the experimental values. All these results could help to provide
valuable data for developing the present porous magnesium for potential bio
applications.
PMID- 27498425
TI - PLA-grafting of collagen chains leading to a biomaterial with mechanical
performances useful in tendon regeneration.
AB - With the aim to obtain a scaffold with improved mechanical properties with
respect to collagen for tendon augmentation and regeneration, a novel collagen
based material was prepared via heterogeneous phase derivatization of type I
collagen sponges using polylactic acid. Compared to the untreated collagen, the
functionalized sponge (Coll-PLA) was characterized by higher tensile properties
and lower swelling capability; the degradation rate of Coll-PLA, in the presence
of collagenase, was lower than that of the untreated collagen sponge. These
results are related to an increased hydrophobic character of the collagen matrix
due to the presence of PLA chains. In vitro tests, performed with human primary
fibroblasts, showed that cell adhesion and proliferation rate on Coll-PLA were
comparable to those obtained with the non-functionalized collagen. These findings
suggest that the new biomaterial could be suitable as scaffold in tendon
augmentation and regeneration.
PMID- 27498426
TI - Rheological, mechanical and degradable properties of injectable chitosan/silk
fibroin/hydroxyapatite/glycerophosphate hydrogels.
AB - Silk fibroin (SF) and hydroxyapatite (HA) were incorporated into
chitosan/glycerophosphate (GP) system to prepare new types of hydrogels. The
formulated chitosan/SF/GP and chitosan/SF/HA/GP solutions were found to be
injectable at room temperature, and able to form into hydrogels at near
physiological temperature and pH. Rheological measurements showed that elastic
modulus of certain chitosan/SF/GP and chitosan/SF/HA/GP gels could reach around
1.8 and 15kPa, respectively, and was much higher than their respective viscous
modulus. Compressive measurements revealed that some chitosan/SF/GP and
chitosan/SF/HA/GP gels had 8 and 20-fold modulus and strength higher than the
chitosan/GP gel, respectively, confirming that compressive properties of these
gels were greatly improved. Results obtained from in vivo degradation
demonstrated that degradation endurance of the optimized chitosan/SF/GP and
chitosan/SF/HA/GP gels was significantly enhanced as compared to the chitosan/GP
gel, and the degradation rate of the gels could be regulated by the SF component
alone or by the combination of SF and HA components.
PMID- 27498427
TI - Fracture characteristics of PEEK at various stress triaxialities.
AB - Polyether-ether-ketone (PEEK) is an alternative to metal alloys in orthopaedic
applications. It gives significant advantages including excellent mechanical
properties and non-toxicity. In this work, a set of specimens with different
notched radii were selected to examine the effect of triaxial state of stress on
the fracture behavior of PEEK. Fractographic analysis via scanning electron
microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) further
elucidated the fracture micromechanisms. Distinct fracture patterns were
identified under different stress triaxialities. In addition, the microstructural
inclusion properties in PEEK specimen such as inclusion size and chemical
composition were analysed and determined. Finite element simulations were carried
out to evaluate the correlation of observed fracture characteristics with
different stress triaxialities.
PMID- 27498428
TI - [Not Available].
PMID- 27498429
TI - Update on vaccine-derived polioviruses worldwide, January 2015-May 2016.
PMID- 27498430
TI - Environmental isolation of circulating vaccine-derived poliovirus after
interruption of wild poliovirus transmission, Nigeria, 2016.
PMID- 27498431
TI - Response.
PMID- 27498432
TI - Those were the days....
PMID- 27498433
TI - Letter to the editor.
PMID- 27498434
TI - Leadership and change will bring us resilience.
PMID- 27498435
TI - Introduction of revalidation for nurses and midwives a major success.
PMID- 27498436
TI - So, you think you would like to publish?
PMID- 27498437
TI - A pathway to clinician-led culture change in the operating theatre.
PMID- 27498438
TI - Surgical safety checklists briefings: Perceived efficacy and team member
involvement.
AB - Researchers have shown inconsistencies in compliance, outcomes and attitudes of
surgical team members related to surgical safety checklist briefings. The purpose
of this study was to examine surgical circulator and scrub practitioners'
perceptions of safety checklist briefings and team member involvement, and to
identify potential improvements in the process based on those perceptions. An
anonymous survey was conducted with members of the Association of periOperative
Registered Nurses (AORN) and the Association of Surgical Technologists (AST).
Questions focused on perceptions of checklist briefing efficacy and team member
involvement in safety practices. From the 346 usable responses, a third
respondent group of self-identified perioperative leaders emerged. Significant
results were obtained related to leaders' perceptions, post-procedure briefings
and various perceptions of team member involvement. Study results indicate that
variances in safety practices continue as perceived by surgical team members thus
presenting opportunities for further examination and improvement of processes in
reducing surgical errors.
PMID- 27498439
TI - One step closer to safer surgery--The National Safety Standards for Invasive
Procedures (NatSIPPs).
PMID- 27498441
TI - Consenting patients with femoral neck fractures--how well are we involving the
patient's relatives?
AB - The consent process is a vital part of the in-patient journey for patients
admitted with a fractured neck of femur. However, an aspect that is frequently
over-looked is the involvement of a patient's next of kin. We organised a pilot
study in our institution to see what steps we could take to make improvements in
the way that next of kin involvement was managed, in line with widespread
national guidelines.
PMID- 27498440
TI - Nursing postoperative visit as a quality indicator for surgical patient care.
AB - The postoperative visit as a quality indicator for surgical patient care, demands
some consideration from perioperative nurses. We evaluated the nursing
perioperative interventions on postoperative visits, and adjusted them to the
needs of the patients with postoperative pain. Our study indicated that 73% of
patients visited didn't have postoperative pain whereas 27% had pain. The pain is
aggravated when the patient is mobilised, one of the most common signs and
symptoms being gastrointestinal changes. Pharmacological and non-pharmacological
measures were used in pain management. The results showed that the percentage of
patients with postoperative visits needs to be improved. We aim to have high
quality perioperative nursing interventions which raise levels of patient
satisfaction.
PMID- 27498442
TI - Leucocyte count indicates carotid plaque instability in stroke patients.
AB - BACKGROUND/AIM: Increasing evidence points to the inflammatory character of
atherosclerosis and several parameters of inflammation have been proposed as
cerebrovascular risk markers. The objective of the research was to examine the
connection of serum inflammatory parameters and ultrasound (US) characteristics
of the structure and size of carotid plaque. We assumed that the number of
leukocytes (Le) was an indicator of carotid plaque instability and an increased
risk of stroke. METHODS: Serum inflammatory parameters: erythrocyte sedimentation
rate in the first (ESR I) and second hour (ESR II), the number of Le, high
sensitivity C-reactive protein (hsCRP) and fibrinogen were measured by standard
methods. All the subjects (n = 75) were divided into 3 groups (symptomatic,
asymptomatic and control). US evaluation of extracranial carotid arteries was
performed in a duplex system. Plaques were classified into categories according
to stenosis percentage (>= 50%, < 50%) and pursuant to echomorphological
characteristics (Gray-Weale classification). In the subjects with stroke an
ischemic lesion was confirmed by computed tomography. RESULTS: The average values
of biochemical parameters in the symptomatic group were: ESR I 29.57 +/- 29.87
cm, ESR II 51.60 +/- 36.87 cm, the number of Le 10.10 +/- 3.20 x 109 U/L, hsCRP
8.15 +/- 5.50 mg/L and fibrinogen 4.03 +/- 0.70 g/L. The average values of all
testing biochemical parameters in symptomatic patients were significantly higher
than in the asymptomatic ones and the control group: for ESR I (p < 0.05) and ESR
II (p < 0.05); for the number of Le (p < 0.001); for hsCRP (p < 0.001) and
fibrinogen (p < 0.001). Category I of echomorphological characteristics in the
symptomatic group was present in 66.7% of the cases and it was significantly
higher than in the asymptomatic (40.0%; p < 0.05) and the control group (20.0%; p
< 0.01). Univariate logistic regression analysis confirmed that all testing
biochemical parameters are indicators of stroke risk. Multivariate logistic
regression analysis confirmed a statistically significant correlation of the
number of Le and stroke risk, while the increase in the value by a unit of
measurement was associated with the growth of risk by 3.22 times (from 1.67 to
6.22). CONCLUSION: The number of Le is associated with the phenomenon of carotid
plaque instability and may be a useful additional marker of increased risk for
developing acute cerebral infarction.
PMID- 27498443
TI - Comparison of cefixime and amoxicillin plus metronidazole in the treatment of
chronic periodontitis.
AB - BACKGROUND/AIM: Despite significant advances in current medicine and improvement
of overall health education, chronic periodontitis is still a widespread disease.
Losing teeth is the most serious complication of this particular illness. The aim
of this study was to examine patients with chronic periodontitis in order to
evaluate the efficacy of non-surgical therapy and combination of amoxicillin and
metronidazole compared with cefixime, which has not been so far used for the
treatment of this disease. METHODS: Adult patients with chronic periodontitis (n
= 90) underwent non-surgical periodontal treatment (zero-day) and then randomly
divided into three groups. The group I served as a control, the group II was
additionally treated with the combination of amoxicillin and metronidazole (for 7
days), while the group III was treated with cefixime (also for 7 days). To assess
the condition of periodontium before and seven days after the therapy, four
clinical parameters were used: gingival index (GI), bleeding on probing (BOP),
probing depth (PD) and clinical attachment level (CAL). RESULTS: On the day 7
after the beginning of the therapy, we found that all the three groups of
patients had statistically significant clinical improvement of three parameters:
GI, BOP and PD, but not of the CAL. However, the improvement of PD was only
statistically, but not clinically significant. The improvement in the control
group of patients on the day 7 was 19% in BOP and 28% in GI; this improvement was
statistically highly significant after the addition of amoxicillin plus
metronodazole (71% in BOP and 77% in GI) or cefixime (62% in BOP and 82% in GI).
Compared to the combination of amoxicillin and metronidazole, cefixim was
statistically significantly more effective for GI (p < 0.05), while for the other
three clinical parameters their effects were equal. CONCLUSION: The conjunction
of amoxicillin plus metronidazole or cefixime to the causal treatment of patients
with chronic periodontitis led to statistically significant improvement in
efficacy in relation to GI and BOP parameters, while cefixime was statistically
significantly more efficient than the combination of amoxicillin and
metronidazole for GI.
PMID- 27498445
TI - Modelling and assessment of the electric field strength caused by mobile phone to
the human head.
AB - BACKGROUND/AIM: Electromagnetic field exposure is the one of the most important
physical agents that actively affects live organisms and environment. Active use
of mobile phones influences the increase of electromagnetic field radiation. The
aim of the study was to measure and assess the electric field strength caused by
mobile phones to the human head. METHODS: In this paper the software "COMSOL
Multiphysics" was used to establish the electric field strength created by mobile
phones around the head. RESULTS: The second generation (2G) Global System for
Mobile (GSM) phones that operate in the frequency band of 900 MHz and reach the
power of 2 W have a stronger electric field than (2G) GSM mobile phones that
operate in the higher frequency band of 1,800 MHz and reach the power up to 1 W
during conversation. The third generation of (3G) UMTS smart phones that
effectively use high (2,100 MHz) radio frequency band emit the smallest electric
field strength values during conversation. The highest electric field strength
created by mobile phones is around the ear, i.e. the mobile phone location. The
strength of mobile phone electric field on the phantom head decreases
exponentially while moving sidewards from the center of the effect zone (the
ear), and constitutes 1-12% of the artificial head's surface. CONCLUSION: The
highest electric field strength values of mobile phones are associated with their
higher power, bigger specific energy absorption rate (SAR) and lower frequency of
mobile phone. The stronger electric field emitted by the more powerful mobile
phones takes a higher percentage of the head surface. The highest electric field
strength created by mobile phones is distributed over the user's ear.
PMID- 27498444
TI - Patterns of prescription antihypertensive drug utilization and adherence to
treatment guidelines in the city of Novi Sad.
AB - BACKGROUND/AIM: Hypertension is one of the leading causes of cardiovascular
morbidity and mortality and more than a half of all health insurance expenditures
for reimbursed medicines are allocated to antihypertensive drugs in Serbia. The
aim of this study was to identify the antihypertensive drug utilization patterns
among hypertensive outpatients in the city of Novi Sad, Serbia, determine the
adherence to clinical guidelines and address the economic aspects of current
prescribing practices. METHODS: This retrospective observational study was
conducted in Novi Sad over a period of six months. The data on the number of
packages, size their, and retail price of antihypertensives issued on
prescription in outpatients with the diagnosis of essential arterial hypertension
was collected from all state-owned pharmacies in Novi Sad. Drug consumption was
analyzed using the Anatomical Therapeutic Chemical (ATC)/ defined daily dose
(DDD) methodology. RESULTS: Total consumption of antihypertensives issued on
prescription over a 6-month period in the city of Novi sad, Serbia was 283.48 DDD
per 1,000 inhabitans per day (DID). Angiotensin converting enzyme inhibitors
(ACEi) were most commonly prescribed drugs, and were used 3 times more often than
calcium channel blockers and 5 times more than beta-blockers. The consumption of
diuretics and angiotensin receptor antagonists was low within all the groups of
outpatients. Both national and international guidelines state superiority and
effectiveness of diuretics in treatment of hypertension in the elderly, but their
consumption was unreasonable low despite the fact that over 70% of all
antihypertensive drugs in the city of Novi Sad were dispensed in people aged >
60. The use of more expensive ACEi was observed despite the guidelines deeming
all the drugs of this class equally effective in treatment of hypertension.
CONCLUSION: Large differences in utilization of different groups of
antihypertensive agents were noted in this study. Underutilization of valuable,
efficacious, and cost-effective thiazide diuretics and overuse of expensive ACE
inhibitors is unjustifiable. There is a potential for large savings with
switching to low-price ACEi, modeling the practice of Scandinavian countries.
PMID- 27498446
TI - Marketing communication in the area of breast and cervical cancer prevention.
AB - BACKGROUND/AIM: Innovative marketing campaigns and promotional activities can
successfully contribute to the improvement of public health by raising the level
of general knowledge about health issues and benefits that the change of habits,
eradication of undesirable behaviour and regular medical controls have. The focus
should be on continuous marketing communication through various mass media or
direct communication between medical staff and patients. The aim of this paper
was to define the role that various communication channels have in the process of
informing and educating the target group in case of breast and cervical cancer
prevention. METHODS: The survey based on polling a sample of 2,100 female
patients of the Serbian Railways Medical Centre was conducted in the period
October- December 2013. The questionnaire included questions about demographic
characteristics, prevention habits of women, their level of information on that
topic and communication channels they prefer. RESULTS: There is a difference
among respondents' awareness level about preventive measures depending on
demographic and geographical criteria. The results indicate the existence of
variations in frequency of performing gynaecological examinations and Pap tests
depending on different age, educational and residential groups. Although the
largest percentage of women stated familiarity with the way of performing breast
self-examination (78%), the majority of them had never performed mammography or
ultrasonography (67%). The greatest number of women were informed about the
possibility of preventing breast and cervical cancer by posters or brochures in
health institutions (71%) and mass media--television on the first place (74%),
then specialized magazines about health (48%), radio (48%), web sites about
health (42%), and daily newspapers (34%). The respondents consider the Ministry
of Health and health institutions as the most responsible subjects for education
of women about cancer prevention, while the self-initiative was given the least
importance. CONCLUSION: Determined informing habits of the target group, their
prevention habits and attitudes on the subject should be used as the basis for
planning and implementation of prevention marketing campaigns that would be the
most effective.
PMID- 27498447
TI - Fever of unknown origin--diagnostic methods in a European developing country.
AB - BACKGROUND/AIM: Fewer of unknown origin (FUO) remains amongst the most difficult
diagnostic dilemmas in contemporary medicine. The aim of this study was to
determine the causes of FU and to identify the methods of diagnosis in patients
with FUO in a tertiary care setting in the Republic of Macedonia. METHODS:
Retrospectively histories of 123 immunocompetent patients older than 14 years
with classical FUO that had been examined at the University Hospital for
Infectious Diseases and Febrile Conditions in the city of Skopje, during the
period 2006-2012 were evaluated. FUO was defined as axillary fever of >= 37.5
degrees C on several occasions, fever duration of more than 21 days and failure
to reach the diagnosis after the initial diagnostic workup comprised of several
defined basic investigations. RESULTS: Infections were the cause of FUO in 51
(41.5%) of the patients, followed by non-infective inflammatory disorders (NIID)
in 28 (22.8%), miscellaneous in 12 (9.7%) and neoplasm in 11 (8.9%) of the
patients. Twenty one of the patients (17.1%) remained undiagnosed. The most
common causes for FUO were visceral leishmaniasis, abscesses, urinary tract
infections, subacute endocarditis, polymyalgia rheumatica and adult onset of
Still disease. The final diagnosis was reached with histology in 24 (23.5%),
imaging and endoscopic procedures in 21 (20.6%), clinical course and empiric
therapy response in 20 (19.6%), serology in 18 (17.6%) and cultures in 16 (15.7%)
of the cases. CONCLUSION: In the Republic of Macedonia infections are the leading
cause of FUO, predominately visceral leishmaniasis. In the future in patients
with prolonged fever, physicians should think more often of this disease, as well
as of the possibility of atypical presentation of the common classical causes of
FUO.
PMID- 27498448
TI - Quantitative morphometric analysis of the myenteric nervous plexus ganglion
structures along the human digestive tract.
AB - BACKGROUND/AIM: All the functions of the digestive system are controlled, guided
and initiated by the autonomic nervous system. A special part of this system
placed in the wall of the gastrointestinal tract is known as the enteric or
metasympathetic nervous system. The aim of this study was to analyse myenteric
nervous plexus in different parts of the digestive tract. METHODS: We examined
the myenteric nervous plexus of the esophagus, stomach, duodenum, jejunum, ileum,
transverse colon and rectum in tissue samples taken from 30 cadavers of persons
aged 20-84 years. After standard histological processing sections were stained
with hematoxylin-eosin, cresyl violet (CV) and AgNO3 method. Multipurpose test
system M42 was used in morphometric analysis. The results were analyzed by t-test
and analysis of variance. RESULTS: The number of neurons per cm2 surface was the
lowest in the esophagus (2.045 +/- 310.30) and the largest in the duodenum
(65,511 +/- 5,639). The statistical processing showed significant differences (P
< 0.001) in the number of neurons between the esophagus and all other parts of
the digestive tract. The maximal value of the average surface of the myenteric
nervous plexus neurons was observed in the esophagus (588.93 +/- 30.45 um2) and
the lowest in the stomach (296.46 +/- 22.53 um2). CONCLUSION: There are
differences in the number of ganglion cells among different parts of the human
digestive tract. The differences range from a few to several tens of thousands of
neuron/cm2. The myenteric nervous plexus of the esophagus was characterized by a
significantly smaller number of neurons but their bodies and nuclei are
significantly larger compared to other parts of the digestive tract.
PMID- 27498449
TI - Efficacy of external warming in attenuation of hypothermia in surgical patients.
AB - BACKGROUND/AIM: Hypothermia in surgical patients can be the consequence of long
duration of surgical intervention, general anaesthesia and low temperature in
operating room. Postoperative hypothermia contributes to a number of
postoperative complications such as arrhythmia, myocardial ischemia,
hypertension, bleeding, wound infection, coagulopathy, and prolonged effect of
muscle relaxants. External heating procedures are used to prevent this condition.
The aim of this study was to evaluate the efficiency of external warming system
in alleviation of cold stress and hypothermia in patients who underwent major
surgical procedures. METHODS: The study was conducted in the Military Medical
Academy in Belgrade. A total of 30 patients of both genders underwent abdominal
surgical procedures, randomly divided into two equal groups: the one was
externally warmed using warm air mattress (W), while in the control group (C)
surgical procedure was performed in regular conditions, without additional
warming. Oesophageal temperature (Te) was used as indicator of changes in core
temperature, during surgery and awakening postoperative period, and temperature
of control sites on the right hand (Th) and the right foot (Tf) reflected the
changes in skin temperatures during surgery. Te and skin temperatures were
monitored during the intraoperative period, with continuous measurement of Te
during the following 90 minutes of the postoperative period. Heart rates and
blood pressures were monitored continuously during the intraoperative and
awakening period. RESULTS: In the W group, the average Te, Tf and Th did not
change significantly during the intraoperative as well as the postoperative
period. In the controls, the average Te significantly decreased during the
intraoperative period (from 35.61 +/- 0.35 degrees C at 0 minute to 33.86 +/-
0.51 degrees C at 120th minute). Compared to the W group, Te in the C group was
significantly lower in all the observed periods. Average values of Tf and Th
significantly decreased in the C group (from 30.83 +/- 1.85 at 20th minute to
29.0 +/- 1.39 degrees C at 120th minute, and from 32.75 +/- 0.96 to 31.05 +/-
1.09 degrees C, respectively). CONCLUSION: The obtained results confirm that the
external warming using warm air mattress was able to attenuate hypothermia, i.e.
substantial decrease in core temperature, compared with the similar exposure to
cold stress in the control group.
PMID- 27498450
TI - The assessment of the stability of the corneal structure after LASIK correction
of myopia by different optical zone diameters.
AB - BACKGROUND/AIM: Enlargement of optical zone (OZ) diameter during laser in situ
keratomileusis (LASIK) correction of myopia postoperatively improves the optical
outcome, however, it also leads to the increased stroma tissue consumption-
progressive corneal thinning. The aim of this investigation was to present the
possibility of safe OZ enlargement without impairing the structural stability of
the cornea, while obtaining an improved optical outcome with LASIK treatment of
short-sightedness. METHODS: Preoperative assessment of the cornea structure and
prediction of the ablated stroma tissue consumption was conducted in 37 patients
(74 eyes) treated for short-sightedness by means of the LASIK method. With the
eyes that, according to their cornea structure, had the capacity for OZ diameter
enlargement of 0.5 mm, LASIK treatment was performed within the wider OZ diameter
of 7.0 mm compared to the standard 6.5 mm. The following two groups were formed,
depending on the diameter of the utilized OZ: the group I (the eyes treated with
the OZ 6.5 mm, n = 37) and the group II (the eyes treated with the OZ 7.0 mm, n =
37). RESULTS: No significant difference in the observed structural parameters of
the cornea was detected between the groups of patients treated with different OZ
diameters. The values of all the parameters were significantly bellow the
threshold values for the development of postoperative ectasia. CONCLUSION:
Diameter enlargement of the treated OZ, if there is a preoperative cornea
capacity for such enlargement, will not impair the postoperative stability of the
cornea structure, and will significantly improve the optical outcome.
PMID- 27498451
TI - New metaphysics in Serbian rehabilitation medicine.
PMID- 27498452
TI - Pheochromocytoma of the urinary bladder--A case report.
AB - INTRODUCTION: Pheochromocytoma of the urinary bladder is a rare tumor and
presents less than 0.06% of all urinary bladder tumors. CASE REPORT: We presented
a 49-year-old female patient with a history of daily paroxysmal hypertension
accompanied with flushing of the face and upper chest, palpitations and excessive
sweating prior to micturition. Ultrasonography reported a 3 cm bladder wall
tumor. The 131I-metaiodobenzylguanidine (131I-MIBG) scan showed a pathological
isotope accumulation in the projection of the bladder. The patient underwent a
partial cystectomy. One year following the operation the patient was normotensive
and without recurrence. CONCLUSION: The most efficient treatment option for
bladder pheochromocytoma is surgical resection. The most important fact in the
diagnostics is suspicion on this rare condition.
PMID- 27498453
TI - A series of drawings of a patient with schizophrenia-like psychosis associated
with epilepsy: captured illustration of multifaced self- expression.
AB - INTRODUCTION: Drawings may give an insight into the complex mental process,
however they have been underutilized in patients with psychosis associated with
epilepsy. CASE REPORT: A 33-year-old, right handed female, diagnosed with
schizophrenia-like psychosis associated with epilepsy, was treated in the Day
Unit due to psychosocial rehabilitation. Besides other treatments, the patient
underwent group analysis of drawings once a week. Qualitative analysis of the
form and content of drawings made by free associations were performed. The
varying of size and motives with vivid colours and the curve of perspective were
documentated in three figures, followed by the last drawing which was without
such elements. CONCLUSION: A series of drawings of patients with psychosis
associated with epilepsy is needed to record a possible variations and
disturbance of the immediate mental process. Group sessions may additionally
contribute to diminish stigma and enhance psychosocial reintegration.
PMID- 27498454
TI - Clinical use of optical coherence tomography and fractional flow reserve.
AB - INTRODUCTION: The aim of each diagnostic method is to serve as a guide in
deciding about the right patient treatment. During myocardial revascularization
the decision to perform revascularization is usually not easy to make, especially
in case of borderline stenosis. It has been proven that it is not enough to base
morphological evaluation of coronary artery vessel stenosis solely on
angiography. It is necessary to include additional modern diagnostic methods for
functional analysis and detailed morphological analysis using fractional flow
reserve (FFR) and optical coherence tomography (OCT), respectively. CASE REPORTS:
In the first case report we showed the significance of morphological analysis
using OCT and proved that it was not lumen stenosis. The second and the third
case reports showed the complementarity between functional analysis (FFR) and
morphological analysis (OCT) of stenosis in solving a complex coronary disease.
The fourth case report showed the significance of OCT in dealing with the
recurrent stent restenosis. CONCLUSION: By these short case reports we confirmed
that percutaneous coronary intervention (PCI) guided by angiography is definitely
not enough in deciding about myocardial revascularization especially in patients
with a complex coronary disease. In certain cases FFR and OCT procedures can be
complementary methods and improve quality of revascularization, particularly in
case of recurrent in-stent restenosis.
PMID- 27498455
TI - PET/CT fusion in radiotherapy planning for lung cancer--Case reports.
AB - INTRODUCTION: Application of imaging methods, namely computed tomography (CT),
magnetic resonance imaging (MRI) and in recent years positron emission
tomography/computed tomography (PET/CT), and the progress of computer technology
have allowed the construction of effective computed systems for treatment
planning (TPS) and introducing the concept of virtual simulation in 3D conformal
radiotherapy planning. CASE REPORT: We hereby presented two patients with the
diagnosis of non-small cell lung cancer who did PET/CT examination. Both patients
had surgery earlier and local recidives are diagnosed with PET/CT. PET/CT of the
first patient described the focus of intense 18F-fluorodeoxyglucose (18FDG)
accumulation 2.99 x 2.9 x 2.1 cm in diameter in the projection of soft-tissue
volume in the left corner, at operating clips height, corresponding to
metabolically active recurrence of the tumor. Mediastinum and right lung
parenchyma were without focal accumulation of 18FDG. Control PET/CT after 3
months was without detectable focus of intense pathological 18FDG accumulation-
good therapeutic response, (metabolic disease remission). On the other hand, in
the second case PET/CT showed a focus of intense 18FDG accumulation screening in
the scar tissue of the apical part of the right lung, 20 x 16 mm, corresponding
to metabolically active tumor recurrence. In the lung parenchyma on the left and
in the mediastinum no visible focus of intense 18FDG accumulation was descrbed.
Radiography included using 3D conformal radiotherapy with fusion PET/CT scan and
CT simulations. CONCLUSION: PET/CT provides important information for planning
conformal radiotherapy, especially in dose escalation, sparing of organ at risk
and better locoregional control of the disease.
PMID- 27498456
TI - Conflicting interests in biomedical research and medical practice.
PMID- 27498457
TI - A vision for future service provision.
PMID- 27498458
TI - To: all RCM members.
PMID- 27498459
TI - Lords vote to end detention of pregnant immigrants.
PMID- 27498460
TI - Student bursaries consultation.
PMID- 27498461
TI - CONSULTATION INTO NMC CHANGES.
PMID- 27498462
TI - Benefits of continuity of carer.
PMID- 27498463
TI - SHOULD I STAT OR SHOULD I GO?
PMID- 27498464
TI - 30 DAYS TO SAVE YOUR MIDWIFERY COMMITTEE.
PMID- 27498465
TI - Challenging times ahead.
PMID- 27498466
TI - 'They were so conditioned against thinking for themselves, because the penalties
were so severe'.
PMID- 27498467
TI - THE BREAST START TO LIFE.
PMID- 27498469
TI - Reply FROM RCM DIRECTOR FOR ENGLAND JACQUE GERRARD.
PMID- 27498468
TI - Incontinence advert gripe.
PMID- 27498470
TI - Research request.
PMID- 27498471
TI - THEY DON'T TELL YOU.
PMID- 27498472
TI - Hang on to your vision.
PMID- 27498473
TI - Yes, my lady.
PMID- 27498474
TI - Exploring midwives' experience of public health in maternity care.
PMID- 27498475
TI - Reducing the length of postnatal hospital stay.
PMID- 27498476
TI - PART ONE. How to ... build and develop a birth centre.
PMID- 27498477
TI - The next generation game.
PMID- 27498478
TI - Taking kangaroo care to China.
PMID- 27498480
TI - Caring for you.
PMID- 27498479
TI - Rural retreat.
PMID- 27498481
TI - Suffering in silence.
PMID- 27498482
TI - Resourcing the public health role.
PMID- 27498483
TI - The road to revalidation.
PMID- 27498484
TI - Handsets at the ready.
PMID- 27498485
TI - With a little help from my friends.
PMID- 27498486
TI - Surviving shift work.
PMID- 27498487
TI - Stillbirth: a renewed focus.
PMID- 27498488
TI - Global village.
PMID- 27498489
TI - Understanding preterm birth.
PMID- 27498490
TI - Evaluation of acetylcholinesterase source from fish, Tor tambroides for detection
of carbamate.
AB - Acetylcholinesterase (AChE) from the brain tissue of local freshwater fish, Tor
tambroides was isolated through affinity purification. Acetylthiocholine iodide
(ATCi) was preferable synthetic substrate to purified AChE with highest maximal
velocity (V(max)) and lowest biomolecular constant (K(m)) at 113.60 Umg(-1) and
0.0689 mM, respectively, with highest catalytic efficiency ratio (V(max)/K(m)) of
1648.77. The optimum pH was 7.5 with sodium phosphate buffer as medium, while
optimal temperature was in the range of 25 to 35 degrees C. Bendiocarp,
carbofuran, carbaryl, methomyl and propoxur significantly lowered the AChE
activity greater than 50%, and the IC50 value was estimated at inhibitor
concentration of 0.0758, 0.0643, 0.0555, 0.0817 and 0.0538 ppm, respectively.
PMID- 27498491
TI - Effects of alternate drip irrigation and superabsorbent polymers on growth and
water use of young coffee tree.
AB - To obtain optimal irrigation management for young coffee tree, the effects of
alternate drip irrigation (ADI) and superabsorbent polymers on physiology,
growth, dry mass accumulation and water use on one-year old Coffea arabica L.
tree were investigated. This experiment had three drip irrigation methods, i.e.,
conventional drip irrigation (CDI), alternate drip irrigation (ADI) and fixed
drip irrigation (FDI), and two levels of superabsorbent polymers, i.e., no
superabsorbent polymers (NSAP) and added superabsorbent polymers (SAP). Compared
to CDI, ADI saved irrigation water by 32.1% and increased water use efficiency
(WUE) by 29.9%. SAP increased root-shoot ratio, total dry mass and WUE by 20.3,
24.9 and 33.0%, respectively, when compared to NSAP. Compared to CDI with NSAP
treatment, ADI with SAP treatment increased total dry mass by 13.8% and saved
irrigation water by 34.4%, thus increased WUE by 73.4%, and it increased root
activity, the contents of chlorophyll and soluble sugar in leaves by 162.4, 38.0
and 8.5%, but reduced the contents of proline and malondialdehyde in leaves by
7.2 and 9.7%, respectively. Thus, alternate drip irrigation with superabsorbent
polymers increased the growth and WUE of young Coffea arabica L. tree and was
optimal irrigation management for young coffee tree.
PMID- 27498492
TI - Evaluating morpho-physiological and quality traits to compliment seed yield under
changing climatic conditions in Brassicas.
AB - A study was conducted under irrigated conditions to test the performance of
improved cultivars of Indian mustard (B. juncea), Gobhi sarson (B. napus) and
African sarson (B. carinata) under changing climatic conditions. The effect of
cultivar, environment and their interactions were significant in mustard and
canola gobhi sarson. Environment had significant impact on all the studied traits
except for leaf area index (LAI). Cultivar x Year (G x Y) interaction was
significant for flowering behavior, days to maturity, SPAD, photosynthetic active
radiations (PAR), growth parameters, yield components and yield except
photosynthesis photochemical efficiency, relative water content (RWC) and LAI.
Cultivar RLC1 surpassed other B. juncea cultivars for yield and had low erucic
acid ('0') while GSL1 (non canola), Hyola PAC401 (hybrid canola) and GSC6
(canola) of B. napus were superior in performance for seed yield and possessed
low erucic and glucosinolate content ('00'). Higher seed yield was associated
with more number of total siliquae/plant, seed weight, biomass, seeds/siliqua,
SPAD and RWC. Correlation coefficient revealed high positive association for seed
yield with days to maturity (0.639**), plant height (0.982**), secondary branches
(0.826**), total siliquae/plant (0.913**), seed weight (0.761**) andbiomass
(0.891**).
PMID- 27498493
TI - The effects of selected pre-treatments on germination of seeds of Oriental
hornbeam (Carpinus orientalis).
AB - In the present study, the effect of some pre-treatments implemented on seeds of
Oriental hornbeam (Carpinus orientalis), which has wide geographical variation
along Turkey on germination percentage values were investigated. For this
purpose, 13 different pre-treatments were implemented to seeds obtained from 17
different populations. According to the obtained results (except control seeds),
pre-treatments leading to lowest germination percentage value (8.1%) in Oriental
hornbeam seeds was PT10: Keeping seeds for 90 min in sulfuric acid, while highest
germination percentage (86.58%) has been obtained with pre-treatment PT13:
Implementation of 40% dose of Baikal EM1 + Biohoumous mixture to the seeds, while
lowest germination percentage (40.50%) was observed on seeds collected from P7
(Bartin-Kozcagiz) population, highest germination percentage was observed in
seeds obtained from P17 (Artvin-Hopa) population.
PMID- 27498494
TI - Impact of acid mine drainage on haematological, histopathological and genotoxic
effects in golden mahaseer, Tor putitora.
AB - The present study was carried out to evaluate sub-lethal mechanism of acid mine
drainage toxicity in fingerlings (9.5 +/- 2.4 cm) of golden mahseer, Tor
putitora. Exposed fingerlings showed significant reduction (P < 0.01) in blood
erythrocytes, neutrophils, thrombocytes, lymphocytes and leukocytes in contrast
to increase in number of immature circulating cells. Hyperplasia, degeneration of
glomeruli, presence of inflammatory cells and increased number of
melanomacrophage aggregates, vacuolization of cell cytoplasm, hepatocyte swelling
were marked in kidney and liver of fish. Ladder in, an increment of 180-200 bp of
hepatic and kidney DNA, by electrophoresis were consistent with DNA damage. 10
day exposure to acid mine drainage resulted in reduction of double stranded DNA
to 46.0 and 48.0 in hepatocytes and kidney cells respectively. Significant
increase (P < 0.01) in tail length and percent tail DNA was evident by comet
assay. The results suggest that exposure to acid mine drainage might cause
irreversible damage to immune cells, tissue and DNA of fish, and this model of
DNA damage may contribute in identifying novel molecular mechanism of interest
for bioremediation application.
PMID- 27498495
TI - Intervarietal variations in various oxidative stress markers and antioxidant
potential of finger millet (Eleusine coracana) subjected to drought stress.
AB - Drought is a major form of abiotic stress leading to lower crop productivity.
Experiment was carried out for selecting the most tolerant genotype among six
different genotypes of finger millet under drought stress. Seeds of six finger
millet genotypes were sown in pots and grown for 35 days. After this period,
drought was induced by withholding watering for stressed plants while control
plants were watered regularly for comparison. Among all six different varieties
of finger millet screened (PR202, PES400, PRM6107, VL283, VL328 and VL149) under
varying intensities of drought stress,PRM6107 and PR202 showed highest stress
tolerance by limiting excessive accumulation of reactive oxygen species (ROS)
through activation of ROS scavenging antioxidative enzymes. A 200% increase in
ascorbate content was recorded in PRM6107 and PR202, while in other varieties
limited increase in ascorbate content was observed. Maximum decrease in
chlorophyll content was observed in VL328 (83%) while least drop was observed in
VL149 (65%). Relative water content indicated that PR202 was able to retain
maximum water content under stress, as it recorded least drop in relative water
content (55%), contributing to its better survival under stress. In conclusion
finger millet genotypes PRM6107 and PR202 possessed maximum drought tolerance
potential and thus may be used for allele mining of drought tolerant genes, which
can further be employed for the development of more drought stress tolerant
staple crops using biotechnological approach.
PMID- 27498496
TI - Assessment of soil characteristics in the vicinity of open cast coal mine and its
suitability for vegetative reclamation in Charhi and Kuju of Jharkhand, India.
AB - Coal mining is inevitable for economic growth of a country, but at the same time
deteriorates the quality of the environment. Open cast mine, especially affects
the top soil most negatively. In the present study, soil samples from three
representative areas of mining viz proposed, operational and abandoned sites from
Charhi and Kuju of Jharkhand were collected and analysed for physicochemical
parameters and metals with an objective to determine their suitability for
vegetative reclamation. Soil samples appeared to be slightly acidic (5.97 +/-
0.66) with low EC values (101 +/- 76 MUScm(-1)), total organic carbon (0.71 +/-
0.35 %), organic matter (1.34 +/- 0.66%) and overall nutrient, especially
nitrogen (167 +/- 64 kg ha(-1)) contents than required for reclamation by
revegetation. However, bulk density was found conducive for reclamation. Total Cr
(317 +/- 287 to 417 +/- 393 mg kg(-1)), Cu (121 +/- 72 to 344 +/- 143 mg kg(-1)),
Ni (171 +/- 46 to 373 +/- 134 mg kg(-1)) and Pb (114 +/- 115 to 182 +/- 145 mg
kg(-1)) content were found to be higher in soil. Sitewise variation was also
significant for Cu and Ni. Pearson's correlation suggested significant (p <=
0.05) positive inter elemental correlation between Cr-Fe, Cr-Mn, Cu-Ni, Fe-Mn and
Mn-Ni. Positive geoaccumulation index (Igeo) values for all the metals except Fe,
overall contamination degree of 31.10 and significant enrichment factor indicated
considerable contamination. This baseline data could be utilized for vegetative
reclamation planning of the study area in future.
PMID- 27498497
TI - Variation in antioxidant enzyme activities, growth and some physiological
parameters of bitter melon (Momordica charantia) under salinity and chromium
stress.
AB - In general, salinity and heavy metals interfere with several physiological
processes and reduce plant growth. In order to evaluate of three levels of
salinity (0, 4 and 8 ds m(-1)) and three concentration of chromium (0, 10 and 20
mg kg(-1) soil) in bitter melon (Momordica charantia), a plot experiment was
conducted in greenhouse at university of Shahrood, Iran. The results revealed
that chromium treatment had no significant affect on fresh and dry weight, but
salinity caused reduction of fresh and dry weight in growth parameter. Salinity
and chromium enhanced antioxidant enzymes activities like catalase (CAT),
guaiacol peroxidase (GPX) and sodium content in leaves. However salinity and
chromium treatments had no effect on potassium, phosphorus in leaves, soluble
carbohydrate concentration in leaves and root, but decreased the carotenoid
content in leaves. On increasing salinity from control to 8 ds m(-1) chlorophyll
a, b and anthocyanin content decreased by 41.6%, 61.1% and 26.5% respectively but
chromium treatments had no significant effect on these photosynthetic pigments.
PMID- 27498498
TI - Assessment of microbial quality of fish processing industrial effluent in bar
mouth at Bhidia landing site, Veraval, Gujarat, India.
AB - The present study was carried out to assess the microbial quality of fish
processing industries effluent at Bhidia bar-mouth, Veraval, Gujarat during
April, 2012 to March 2013. The total viable bacterial count (TVBC), total
Enterobacteriaceae count, E. coli count (EC), Staphylococcus aureus and Fecal
Streptococcal count in effluent ranged from 3.0 x 10(-1) to 6.8 x 10(6), 9.0 x
10(1) to 2.9 x 10(4), 0 to 0. 5 x 10(4), 0 to 0. 4 x 102 and 0.3 x 10(1) to 0. 1
x 10(4) cfu.(-1)respectively. Significantly higher load of TEC, E. coli,
S.aureus, Fecal Streptococci, Total coliforms and Fecal coliforms were higher
during summer whereas, TVBC was higher in the month of Sept.-Oct. Furthermore,
the total coliform and fecal coliform counts were found to be higher with 1400+
/100 ml MPN value throughout the year of the study, except in the month of
August. Overall occurrence of pathogenic strains of E. coli, S. aureus and Fecal
streptococci were 41.67%, 25.00% and 66.67% respectively during this period. The
antibiogram of the isolated E. coli isolates show that almost 50% were resistant
to Cefazidime/Clavulanic acid (CAC), Amoxyclav (AMC), Ciprofloxacin (CIF) and
Ampicillin (AMP). The present study indicated that the effluent of fish
processing industry was heavily contaminated with E. coli, S. aureus and Fecal
Streptococci which confirmed improper treatment of fish processing effluent.
Moreover, the precedence of antibiotic resistant E. coli may pose threat to
public health safety.
PMID- 27498499
TI - Determination and optimization of Vitamin B complex in xylanase enzyme treated
polished rice by response surface methodology.
AB - The present study provides information about the concentrations of Vitamin B
(thiamine, riboflavin, pyridoxine and niacin) in polished brown rice treated with
xylanase. Xylanase enzyme was produced from Aspergillus awamori MTCC 9166. Brown
rice was treated with 60-100% enzyme (40 ml of buffer -undiluted) for 30 to 150
min (with variation of 30 min) at 30 degrees C to 50 degrees C (with variation of
5 degrees C) to attain a saturated moisture level of 35.5 g100(-1)g .The enzyme
acted upon selective degradation (polishing time 10-50 sec) of bran layer
facilitating retention of more vital nutrients along with the vitamins. Vitamin B
content, detected through HPLC and optimized by response surface methodology
(RSM) with central composite design (CCRD), demonstrated that selective
degradation of bran layers for polished rice facilitated increase of thiamine
(57%), riboflavin (48%), pyridoxine (90%) and niacin (55%) concentration in bio
polished rice over normally milled rice.Enzyme treated bio-polished rice was
considered to be better source of vitamin B complex than mechanically milled
rice, hence more nutritionally efficacious.
PMID- 27498500
TI - Comparative evaluation of cyanide removal by adsorption, biodegradation, and
simultaneous adsorption and biodegradation (SAB) process using Bacillus cereus
and almond shell.
AB - The present study aimed to investigate the removal efficiency of cyanide from
contaminated water by adsorption, biodegradation and simultaneous adsorption and
biodegradation (SAB) process individually in a batch reactor. Adsorption was
achieved by using almond shell granules and biodegradation was conducted with
suspended cultures of Bacillus cereus, whereas SAB process was carried out using
Bacillus cereus and almond shell in a batch reactor. The effect of agitation
time, pH, and initial cyanide concentration on the % removal of cyanide has been
discussed. Under experimental conditions, optimum removal was obtained at pH 7
with agitation time of 48 hrs and temperature of 35 degrees C. Cyanide was
utilized by bacteria as sole source of nitrogen for growth. The removal
efficiencies of cyanide by adsorption, biodegradation, and SAB were found to be
91.38%, 95.87%, and 99.63%, respectively, at initial cyanide concentration of 100
mg l(-1). The removal efficiency of SAB was found to be better as compared to
that of biodegradation and adsorption alone.
PMID- 27498501
TI - Adhesive bond performance of heat-treated wood at various conditions.
AB - Heat treatment of wood leads to chemical, structural and physical changes in wood
constituents, which can significantly affect the bonding performance of wood in
several ways depending on the adhesive type used. In the present study, fir
(Abies bornmulleriana Mattf.) and beech (Fagus orientalis L.) were heat treated
at 170 degrees C, 180 degrees C, 190 degrees C, 200 and 212 degrees C for 2
hours. Four different types of adhesives were used for bonding process: melamine
urea-formaldehyde (MUF), melamine formaldehyde (MF), phenol formaldehyde (PF),
and polyurethane (PUR). For all the pretreatment conditions, highest shear
strength of adhesive bonds of each adhesive system was observed for untreated
samples and shear strength decreased with increasing heat treatment. The strength
of each adhesive bond of samples which were soaked in water was much less than
dry samples, approximately half of the dry strength. Generally, the shear
strength of the adhesive bonds after boiling was smaller than or similar to the
values obtained for soaking. The untreated samples lost more strength after
soaking and boiling than heat treated samples. With increasing heat treatment
severity, reduction in shear strength increased in dry samples while decreased in
soaking and boiling samples. For instance, after soaking, the untreated samples
lost more strength (almost 39%) than heat treated samples (almost 24% for most
severely heat treated samples). The results showed that the shear strength of
adhesive bonds was influenced by heat treatment and depended on pretreatment of
samples prior to testing. In general, all adhesives used performed in quite a
similar way for all pretreatment conditions, and the bonding performance of heat
treated fir wood was less satisfactory than that of beech wood for all adhesive
system and condition.
PMID- 27498502
TI - Isolation and identification of gold nanoparticles synthesizing fungi from Indian
Kolar Gold Field mine soil.
AB - An indigenous fungal strain was isolated from Indian Kolar Gold Field mine soil.
The isolate was heterothallic, branched septate, deeply floccose, fast-growing,
dull green with white background conidial columnar mycelium from Aspergillus
section Fumigati. Diverse metabolic patterns of the isolate exhibit high metal,
thermal resistance which grews well from 28 +/- 1 degrees C to 37 degrees C and
pH concentration was significant on the growth of isolate. Phylogenetic analysis
of 16srRNA beta-Tubulin gene sequence established relationship among isolate and
other taxa. Molecular identification and morphological features of fungal isolate
were consistent with those of Neosartorya udagawae. Heterothallic N. udagawae
FJ830683 strain was closely related to homothallic N. aureola EF661890. Fungal
isolate extract synthesized narrow sized stable Gold nanoparticles (AuNPs).
PMID- 27498503
TI - Morphometric relations in the grey eel catfish Plotosus canius in the coastal
waters of Port Dickson, Peninsular Malaysia.
AB - Samples of grey eel catfish Plotosus canius were collected from the coastal
waters of Port Dickson, Malaysia from January to December, 2012. A total of 341
specimens (172 males and 169 females) were used to estimate the length-weight
relationship parameters. Mean population size of females were 0.72 cm taller than
the males, however difference was not significant (t-test, P > 0.05). The overall
relationship equations between total length (TL) and body weight (BW) were
established for males as Log TW = 2.71 Log TL - 1.85 (R2 = 0.95) and for females
as Log TW = 2.88 Log TL-2.10 (R2 = 0.95). The estimated relative growth co
efficient (b) values were 2.71 for males and 2.88 for females. It is revealed
that growth pattern of the species showed negative allometry. In both males and
females, relationship between TL and SL gave highest regression coefficient
(0.99). While relationship between TL and EL gave lowest regression coefficient
in both males and females (0.87 and 0.81 respectively). The findings from this
study contributed first information on morphometric relations of the fish from
Malaysian coastal waters and could be useful for sustainable management options
of P. canius in Malaysia.
PMID- 27498504
TI - Biochemical and molecular dissection of thermo-sensitive genetic male sterility
in diploid cotton (Gossypium arboreum L).
AB - Diploid cotton, due to its inherent problem of stamen brittleness, its found
unsuitable for traditional method of hybrid seed production which involves hand
emasculation followed by pollination. Due to shortfall in other methods viz.,
Genetic Male Sterility (GMS), as well as, Cytoplasmic Genetic Male Sterility
(CGMS), hybrid seed production in diploid cotton becomes costly and thereby,
covers less area among the total cotton grown area. Thermo-sensitive genetic male
sterility, which overcomes the drawbacks of both GMS and CGMS can be an effective
tool in coming years for hybrid cotton research. Understanding fertility and
sterility variations, their relation with biochemical changes in plant is
important before its application in plant breeding. Hence, the available TGMS
line, Ga TGMS-3 obtained at Cotton Research Centre, UAS, Dharwad was studied for
callase activity and markers associated with TGMS. The line Ga TGMS-3 had fertile
anthers and showed less callase enzyme activity at pre-meiosis stage, high enzyme
activity at tetrad releasing microspore stage and no callase activity during
other stages. The counterpart TGMS sterile anthers displayed little higher
callase activity at pre-meiosis stage, high activity at tetrad stage, but poor
activity at tetrad releasing microspore stage. During tetrad stage, TGMS sterile
anthers showed high callase enzyme activity giving every chance for early release
of poorly developed microspores as compared to fertile anthers. At tetrad
releasing microspores stage during which fertile anthers had strong callase
enzyme activity led to microspores being released normally and developed normal
pollen grains as compared to sterile anthers. The present investigation revealed
that NAU2176, NAU2096 and BNL1227 primers can be used as tightly linked markers
for TGMS trait, as evident from their differential expression in fertile and
sterile anthers.
PMID- 27498505
TI - Studies on monitoring the heavy metal contents in water, sediment and snail
species in Latipada reservoir.
AB - The concentrations of zinc, copper, cadmium and lead in surface water, sediments
and two native snail species, Bellamya bengalensis and Melanoides tuberculata
from Latipada reservoir were determined. The concentrations of cadmium and lead
in surface water were higher than the WHO recommended limits for drinking water
standards; where as those of zinc and copper were within the permissible limits.
The concentrations of zinc, copper, cadmium and lead were higher in sediments
than in water. The observed bioaccumulated level of zinc, copper, cadmium and
lead in Bellamya bengalensis were Zn- 197.22, Cu- 172.14, Cd- 11.59 and Pb-
112.57 MUg g(-1), while in Melanoides tuberculata were Zn- 136.59, Cu- 132.04, Cd
13.25 and Pb- 27.69 MUg g(-1). The metal concentrations in both species of
snails were higher than those of the water and sediment. Bioaccumulated metal
concentrations, Bio-Water Accumulation Factor (BWAF) and Bio-Sediment
Accumulation Factor (BSAF) values indicated that Bellamya bengalensis had high
potential for zinc, copper and lead bioaccumulation than Melanoides tuberculata,
while Melanoides tuberculata had high potential for cadmium than Bellamya
bengalensis. Therefore, Bellamya bengalensis is proposed as sentinel organism for
monitoring zinc, copper and lead, while Melanoides tuberculata for monitoring
cadmium in freshwater.
PMID- 27498506
TI - Effect of fermented earthworm cast on egg production and egg quality as well as
removal of odor in feces from egg laying hens.
AB - The objective of the present study was to determine the effect of feeding
fermented earthworm casts (EEC) to layers on egg-laying performance, blood lipid
profiles, cecal microflora, and fecal odor removing performance. A total of 200
Hyline Brown layer chicks at 33-week-old were used in this study. They were
randomly assigned to two numerically equal groups with 100 replications per
treatment for 10 weeks. All the birds were caged individually. The control group
was not treated with EEC. The EEC group was treated with top dressing containing
3.5% EEC. The present study revealed that egg production and egg weight were
increased after feeding diet containing EEC at the top dressing level. Haugh
unit, eggshell thickness, and eggshell breaking strength of EEC group were higher
than those of control group. Egg yolk was determined for fatty acid profiling. It
was found that EEC group had higher ratio of unsaturated- to saturated fatty acid
as compared to control group. Lower ratios of n-6 to n-3 fatty acids were found
in the egg yolk of EEC group. Plasma triglyceride and total cholesterol contents
were lower in the EEC group. However, high density lipoprotein-cholesterol
content was higher in the EEC group as compared to that in control group. The
number of cecal Lactobacillus was increased while the population of Escherichia
coli and coliform bacteria decreased in the EEC group. Fecal ammonia and hydrogen
sulfide contents were lower in the EEC group as compared to those in control
group. Taken together, these results suggested that EEC could improve egg
production and egg quality. In addition, it could remove odour from laying-hen
manure.
PMID- 27498507
TI - In vitro evaluation of Pseudomonas bacterial isolates from rice phylloplane for
biocontrol of Rhizoctonia solani and plant growth promoting traits.
AB - The ability for biocontrol and plant growth promotion of three Pseudomonas
bacterial isolates namely Pseudomonas fluorescens (UMB20), Pseudomonas aeruginosa
(KMB25) and Pseudomonas asplenii (BMB42) obtained from rice plants was
investigated. Fungal growth inhibition by the isolates ranged from 86.85 to
93.15% in volatile and 100% in diffusible metabolites test. Among the isolates,
BMB42 showed fungal growth inhibition significantly in the volatile metabolite
test. Isolates UMB20 and BMB42 were able to synthesis chitinase with chitinolytic
indices of 13.66 and 13.50, respectively. In case of -1,3-glucanase, all the
isolates showed activity to produce this enzyme at varied levels and isolate
KMB25 showed significantly highest activity (53.53 ppm). Among the three
isolates, KMB25 showed positive response to protease production and all of them
were negative to pectinase and lipase and positive to the production of
siderophore, and HCN, and were able to solubilize tricalcium phosphate. All the
three bacterial isolates were capable of forming biofilm at different levels.
Above results suggest that phylloplane Pseudomonas bacterial isolates have
potential for antifungal activities and plant growth promotion.
PMID- 27498508
TI - Land use change and its effects on water quality in typical inland lake of arid
area in China.
AB - Land-use change is very important for determining and assessing the influence of
human activity on aquatic environment of rivers and lakes. The present work with
Bosten River basin as the subject, analyzes features of dynamic land-use change
of the basin from 1993 to 2013, in order to study the influence of land-use
pattern change on the basin water quality, according to the land-use/land
cover(LUCC) chart from 2000 to 2013 made by ArcGIS and ENVI. It shows cultivated
land, wetland and forestland constitute most of Bosten River basin, taking up
over 41.7% of the total; from 1993-2000, LUCC of the basin is relatively small,
with an increase of cultivated land, residential-industry land, water wetlands by
15.09%-18.33%,most of which are transformed from forestland, grassland and unused
land; from 2000-2013, LUCC of the basin is relatively significant, with a
continuing and bigger increase of cultivated land and Residential-industry area,
most of which are transformed from water wetlands and unused land. Based on
analysis of landuse pattern and water quality index, it can be told that water
pollution is positively correlated to cultivated land and residential-industry
area and negatively correlated to water and grassland. Also, the influence of
land-use pattern change on water quality has been discussed, whose finding can
serve as the scientific evidence for land-use optimization and water pollution
control.
PMID- 27498509
TI - Degradation of acephate by Enterobacter asburiae, Bacillus cereus and Pantoea
agglomerans isolated from diamondback moth Plutella xylostella (L), a pest of
cruciferous crops.
AB - Acephate-degrading bacterial isolates were isolated from the larval gut of
diamondback moth Plutella xylostella, a notorious pest of cruciferous crops
worldwide that has developed resistance to insecticides. Partial 16S rRNA gene
sequencing identified the isolates as Bacillus cereus (PX-B.C.Or), Enterobacter
asburiae (PXE), and Pantoae agglomerans (PX-Pt.ag.Jor). All isolates grew on
minimal media (MM) in the presence of acephate at 100 and 200 ppm, with maximum
growth at 200 ppm. LC-MS analyses of spent medium showed that E. asburiae
degraded acephate to methamidophos and O, O-dimethyl phosporamidate and B. cereus
O,S-dimethyl to phosphorothioate but P. agglomerans to an unnamed compound. All
three isolates used acephate as a source of carbon and energy for growth;
however, P. agglomerans used it also as source of sulphur. Strong evidence
revealed that the bacterial communities present in the gut of diamondback moth
might aid in acephate degradation and play a role in the development of
insecticide resistance.
PMID- 27498510
TI - Under pressure.
PMID- 27498511
TI - Good social interactions help obese children to lose weight.
PMID- 27498512
TI - New NICE guidance on domestic abuse.
PMID- 27498513
TI - Early years sector takes action on oral health.
PMID- 27498515
TI - Swaddling link to SIDS.
PMID- 27498514
TI - UK needs to reduce inequalities, say Unicef.
PMID- 27498516
TI - Dear Prime Minister....
PMID- 27498517
TI - The impact of perinatal loss on parents and the family.
PMID- 27498519
TI - "We need to 'normalise' breastfeeding".
PMID- 27498518
TI - Eczema and infant skin care.
PMID- 27498520
TI - The latest evidence on Lyme disease.
PMID- 27498521
TI - Streets ahead.
PMID- 27498522
TI - Parental response to aType 1 diabetes diagnosis.
PMID- 27498523
TI - The effect of climate change on our heath.
PMID- 27498524
TI - Summer allergies.
PMID- 27498525
TI - A cry for help.
PMID- 27498526
TI - Listen and learn.
PMID- 27498527
TI - EFFICIENCY OF ULTRASOUND GUIDED LOWER LIMB PERIPHERAL NERVE BLOCKS IN
PERIOPERATIVE PAIN MANAGEMENT FOR KNEE ARTHROSCOPY IN CHILDREN. A RANDOMIZED
STUDY.
AB - INTRODUCTION: Ultrasound guided lower limb peripheral nerve blocks are efficient
for perioperative pain treatment in children. The aim was to see if lower limb
peripheral nerve blocks reduced the amount of propofol and opioid analgesics used
intraoperatively, as well as the level of pain and consumption of systemic
analgesics postoperatively. MATERIAL AND METHODS: A randomized, prospective
clinical trial was carried out. It included 60 children between 11 and 18 years
of age scheduled for elective knee arthroscopy. The patients were divided into
two groups. Group A received general anesthesia, group B received lower limb
peripheral nerve blocks with sedation or general anesthesia. Postoperative level
ofpain was assessed using visual analogue scale. RESULTS: Less propofol and
fentanyl was used to induce and maintain anesthesia in group B (p < 0.001). The
level of postoperative pain was significantly lower in group B (p < 0.001), as
well as the postoperative consumption of analgesics (p < 0.001). As mahbny as 47%
of the patients were discharged without receiving any analgesics postoperatively.
The average duration of peripheral nerve blocks was 468 minutes. CONCLUSIONS:
Ultrasound guided lower limb peripheral nerve blocks are an efficient technique
of regional anesthesia in children. They reduce the amount of general anesthetics
and opioid analgesics needed intraoperatively as well as the level of
postoperative pain and consumption of analgesics postoperatively.
PMID- 27498528
TI - DRUG UTILIZATION IN TREATMENT OF THYROID DISORDERS DURING PREGNANCY IN SERBIA.
AB - INTRODUCTION: Depleted uranium radiation and pollution with polychlorinated
biphenyls resulting from bombings the territories of Serbia as well as the
additional long-term stress may have affected the function of thyroid gland. The
objective of this study was to determine the trend of drug utilization in the
treatment of thyroid dysfunction during pregnancy in Novi Sad. MATERIAL AND
METHODS: Women who had given birth at the Department of Gynecology in 1989, 1999,
2007 and 2011 were interviewed during a one-month period about thyroid diseases
in the pregnancy as well as the drugs they had taken. RESULTS: Not a single
pregnant woman was reported to have a thyroid disorder in 1989 and 1999, while in
2007 four women were reported to have a thyroid dysfunction. In 2011, fourteen
out of 18 women with thyroid dysfunction were using levothyroxine and in most
cases hypothyroidism was diagnosed as autoimmune Hashimoto thyroiditis.
CONCLUSION: The study results suggest the necessity of performing more detailed
analyses of the correlation between the frequency of the thyroid gland
dysfunction and the effects of environmental pollution in Serbia.
PMID- 27498529
TI - EXPRESSION OF COLLAGEN TYPE I IN UNALTERED AND OSTEOARTHRITIC MENISCI OF KNEE
JOINT.
AB - INTRODUCTION: Knee osteoarthritis is a progressive degenerative disease which
affects meniscal tissue. The aim of this study was to determine the differences
in collagen type I expression in macroscopically unaltered and osteoarthritic
menisci, and correlate the expression with the grade of macroscopic damage, age
and body mass index of patients, preoperative condition of anterior cruciate
ligament, angulation and knee contracture. MATERIAL AND METHODS: The control
group consisted of 10 macroscopically unaltered menisci, while the experimental
group had 35 osteoarthritic menisci. Besides macroscopic grading of meniscal
damage, the analysis of collagen type I expression was determined by
immunohistochemical staining with the corresponding antibody using
semiquantitative scale scores and quantitative parameters: intensity of
expression and stained area size. RESULTS: The results of semiquantitative
evaluation showed a statistically significant decrease in collagen type I
expression in osteoarthritic menisci, which correlated with an increase in
macroscopic damage grade. The results of quantitative evaluation did not show a
statistically significant decrease in the expression. In posterior meniscal
horns, a more intense collagen type I expression was seen in the women, as well
as a positive correlation of quantitatively evaluated expression with body mass
index. Collagen type I expression in the anterior horns was significantly lower
in varus alignment. CONCLUSION: In the semiquantitative evaluation, collagen type
I expression in osteoarthritic menisci was significantly lower compared to
macroscopically unchanged menisci. The decrease in the expression level
correlates with the increase in the grade of macroscopic meniscal damage. There
was no statistically significant difference in the quantitative evaluation of
expression.
PMID- 27498531
TI - IMPORTANCE OF INTEGRATED MANAGEMENT SYSTEM APPLIED IN HEALTH ESTABLISHMENTS IN
ORDER TO RAISE TREATMENT QUALITY.
AB - INTRODUCTION: The term "management" is best characterized as "managing" economic
or social processes to achieve objectives through a rational use of material and
immaterial resources by applying the principles, functions, and management
methods. This study has been aimed at evaluating the value of an integrated
quality management system implemented at the Institute of Cardiovascular Diseases
of Vojvodina to improve the quality of treatment. MATERIAL AND METHODS: In the
period from 2008 to 2010 about 40 employees from the Institute of Cardiovascular
Diseases of Vojvodina attended various courses given by the lecturers of the
Faculty of Technical Sciences, where the function and significance of the
"International Standards Organization" were explained, after which standards of
interest were implemented at the Institute of Cardiovascular Diseases of
Vojvodina. RESULTS: The Department of Cardiology has introduced 11 cardiac
procedures with 5 special instructions, 14 general procedures, and 7 specific
procedures with 2 instructions. The Department of Cardiac Surgery has introduced
7 procedures to be implemented. The "Vojvodina score" model was put into practice
for the perioperative evaluation of cardiac surgery risk. During 2014, the
Institute of Cardiovascular Diseases ofVojvodina obtained accreditation for the
period of 7 years. CONCLUSION: The integrated quality management system must be
applied in order to achieve a high level of health care in the shortest possible
time and with the least possible consumption of material and human resources. The
application of this system in practice gives a realistic insight into the working
processes and facilitates their functioning. It demands and requires constant
monitoring of the system efficiency along with continuous changes and
improvements of all elements of the working processes and functional units.
PMID- 27498530
TI - ALGORITHM OF OVULATION INDUCTION IN PATIENTS WITH POLYCISTIC OVARY SYNDROME.
AB - INTRODUCTION: Polycystic ovary syndrome is the most frequent endocrine
disturbance in the reproductive period of women's life and the most frequent
cause of anovulatory infertility. Ovulation and pregnancy in patients having
polycystic ovary syndrome may be a result of a wide range of therapeutic options,
and the treatment assumes a gradual approach--from simple noninvasive to
expensive and demanding procedures. MATERIAL AND METHODS: A systematic literature
survey concerning the efficiency of particular ovulation induction methods in
respect of the reproductive outcome was carried out with the aim of establishing
the algorithm for ovulation induction in infertile patients having polycystic
ovary syndrome. The search was confined to clinical investigations performed on
human subjects, reported in English in the period from the beginning of 2010 to
June of 2014. CONCLUSION: As a conclusion of this systematic survey of the
efficiency of ovulation induction methods, which confirms and supplements the
knowledge in this field, it is possible to form the algorithm for ovulation
induction in infertile patients having polycystic ovary syndrome, consisting of
the following subsequent steps: 1) modification of life style, 2) induction with
clomiphene citrate 3) use of metformin, 4) use ofaromatase inhibitors, 5)
application ofgonadotropins and laparoscopic ovarian drilling--as a second-line
treatment, and 6) assisted reproductive techniques.
PMID- 27498532
TI - CHEMOTHERAPY ANALYSIS IN MASSIVE TRANSFUSION SYNDROME.
AB - INTRODUCTION: Massive transfusion is defined as blood transfusion in quantities
equal to or greater than the estimated patients' blood volume over a relatively
short period of time (3-4 hours). The study was aimed at analyzing the
application of chemotherapy in treatment of patients with acute massive bleeding
and evaluating the results of hemostasis and platelet counts screening tests in
the patients receiving massive transfusions. MATERIAL AND METHODS: Attempts were
made to fully compensate hemostatic factors in 24 patients (14 male and 10
female, aged 23 to 76 years) with acute massive and uncontrolled surgical
bleeding (polytrauma, abdominal aortic aneurysm, digestive tract bleeding as a
result of a farina overdose, mortus fetus) over the five-year period, wherein a
circulating patients' blood volume was compensated over a relatively short period
of time. First the surgical bleeding was stopped. The objective of chemotherapy
was the combined use of resuspended red blood cells, fresh frozen plasma,
cryoprecipitates and the platelet concentrate in order to maintain the patients'
normal circulating blood volume and blood pressure (systolic blood pressure >=
100 mmHg) with hemoglobin value higher than 100 g/l and the hematocrit above 0.30
l/l. RESULTS: Transfusion treatment of 24 patients with acute bleeding consisted
of an average of 16 to 18 units of resuspended red blood cells (ranging from
4,880 ml to 5,220 ml); fresh frozen plasma (980 ml to 1,220 ml); cryoprecipitates
(an average of 10 to 15 units i.e. 500-750 ml) and concentrated platelets
(approximately an average of 8 to 12 units i.e. 240 to 360 ml). CONCLUSION: In
our study we have confirmed the pathophysiological mechanism shown in the
available medical literature that after transfusion of a large red blood cell
concentrate volume, dilutional coagulopathy develops, caused by a sharp drop in
platelet count and the significantly reduced activity of unstable coagulation
factors in the patient's circulation.
PMID- 27498533
TI - OTOLOGICAL MANIFESTATIONS OF TURNER SYNDROME: CLINICAL AND RADIOLOGICAL FINDINGS.
AB - INTRODUCTION: Turner syndrome is a chromosomal abnormality where all or a part of
one of the X chromosomes is absent or it has other abnormalities. Besides
characteristic abnormalities of short stature and infertility, women with Turner
syndrome have increased risks for tumors of the central nervous system,
especially meningioma and an otologic disease. Meningioma involving the middle
ear is extremely rare, and this condition has never been published in association
with Turner syndrome. CASE REPORT: We present an otologic manifestation
associated with other abnormalities in a patient with Turner syndrome and discuss
diagnosis and possible treatment options. CONCLUSION: Multidisciplinary team
approach is essential in these patients in order to evaluate their vulnerability
and define therapeutic priorities.
PMID- 27498534
TI - HIDRADENITIS SUPPURATIVA: A CASE SERIES OF EIGHT PATIENTS.
AB - INTRODUCTION: Hidradenitis suppurativa is a persistent, inflammatory and
recurrent disease of the hair follicles which, in time, results in ugly scars.
Inflammation and obstruction of channel of sweat glands used to be thought to be
the basis of this disease. CASE REPORTS: This paper presents the cases of 8
patients operated on in the past 3 years. A possibility of an oversight in making
the diagnosis, as well as an underestimation in the treatment should be taken
into consideration. In addition to surgical methods the authors discuss other
therapeutic possibilities taken from the available literature. This is a
retrospective analysis of the surgical findings. The treatment was
multidisciplinary but the surgical excision was the only option which provided
healing without recurrence so far. In our series the excision could be done to
the fascia or to leave a thin layer of adipose tissue. The reconstruction could
be achieved by healing per secundam, by autologous skin or artificial graft, or
by narrowing the wound with a skin portion. Our results achieved by stage,
secondary stitches and rotation portions were satisfying. CONCLUSION: In case of
advanced disease only surgery can lead to healing. We performed late surgery
because the disease was diagnozed in advanced stages according to Hurlay. Wide
excision was done in all our patients. The reconstruction was achieved with
rotational flap in 3 patients, the wound healing per secundam in 4 patients and
with primary suture in one patient. Our patients did not have recurrences of the
primary disease. The disease was combined in one case with perianal fistula.
PMID- 27498535
TI - ATYPICAL KAWASAKI DISEASE.
AB - INTRODUCTION: Kawasaki disease is an acute vasculitis which occurs primarily in
children under the age of 5. The etiology of the disease is still unknown.
Diagnostic criteria for Kawasaki disease are fever and at least four of the five
additional clinical signs. Incomplete Kawasaki disease should be taken into
consideration in case of all children with unexplained fever for more than 5
days, associated with 2 or 3 of the main clinical findings of Kawasaki disease.
The diagnosis of incomplete Kawasaki disease is based on echocardiographic
findings indicating the involvement of the coronary arteries. Cardiac
complications, mostly coronary artery aneurysm, can occur in 20% to 25% of
untreated patients and in 4% of treated patients. CASE REPORT. In this report we
present a case of atypical Kawasaki disease in a 3.5-month-old infant. As soon as
the diagnosis was made, the patient received high doses of intravenous
immunoglobulin, with the initial introduction of ibuprofen, then aspirin with a
good clinical response. Due to the presence of aneurysm of coronary arteries,
further therapy involved aspirin and clopidogrel over the following 3 months, and
then only aspirin for 2 years. There was a gradual regression of the changes in
the coronary blood vessels to the normalization of the echocardiographic findings
after 2 years. CONCLUSION: Kawasaki disease is the second most common vasculitis
of childhood, so it should be included in the differential diagnosis for any
child with a prolonged unexplained fever. Atypical Kawasaki disease should be
taken into consideration in cases when not all clinical criteria are present but
coronary abnormalities are documented.
PMID- 27498536
TI - HISTOPATHOLOGICAL ANALYSIS AND SURGICAL TREATMENT OF BREAST CANCER--OUR
EXPERIENCE.
AB - INTRODUCTION: The aim of this study was to show the descriptive and
histopathological analysis and applied surgical technique with early and late
post-operative complications in patients with breast cancer who were hospitalized
and treated at the General Hospital in Novi Pazar during the period 2009-2011.
MATERIAL AND METHODS: During the period from 2009 to 2011, 59 patients were
operated for breast cancer at the General Hospital in Novi Pazar. The study
included the size and type of the tumor, disease stage, surgical techniques and
complications, the age of the patients at the moment of surgery and its
correlation with the number of metastatic lymph nodes in the axilla and the tumor
size, as well as the correlation of the tumor size with the number ofmetastases
in the axillary lymph nodes. RESULTS: The dif- ference in the tumor size in
relation to the age among the women under 50 and over 50 years of age was not
statistically significant (T = -1.203, p > 0.05). There was no statistically
significant difference between the number of positive lymph nodes in the women
under and over 50 years of age (Mann-Whitney U test, p > 0.05). A significant
positive correlation between the tumor size and the number of positive axillary
lymph nodes was found (p = 0.308, p < 0.05). A significant positive correlation
of the patient's age and breast cancer stage was also confirmed with
nonparametric variance analysis by Spearman's Rho (p = 0.337, p < 0.05).
CONCLUSION: The majority of women from this study sample were with Stage II of
breast cancer, which points out the necessity for better prevention and education
of women in order to improve early diagnosis of breast cancer. The number of
positive axillary lymph nodes appears to be an important prognostic factor and a
significant positive correlation between the tumor size and the number of
positive axillary lymph nodes has been found.
PMID- 27498537
TI - Mycobacterium sarraceniae sp. nov. and Mycobacterium helvum sp. nov., isolated
from the pitcher plant Sarracenia purpurea.
AB - Several fast- to intermediate-growing, acid-fast, scotochromogenic bacteria were
isolated from Sarracenia purpurea pitcher waters in Minnesota sphagnum peat bogs.
Two strains (DL734T and DL739T) were among these isolates. On the basis of 16S
rRNA gene sequences, the phylogenetic positions of both strains is in the genus
Mycobacterium with no obvious relation to any characterized type strains of
mycobacteria. Phenotypic characterization revealed that neither strain was
similar to the type strains of known species of the genus Mycobacterium in the
collective properties of growth, pigmentation or fatty acid composition. Strain
DL734T grew at temperatures between 28 and 32 degrees C, was positive for 3-day
arylsulfatase production, and was negative for Tween 80 hydrolysis, urease and
nitrate reduction. Strain DL739T grew at temperatures between 28 and 37 degrees
C, and was positive for Tween 80 hydrolysis, urea, nitrate reduction and 3-day
arylsulfatase production. Both strains were catalase-negative while only DL739T
grew with 5 % NaCl. Fatty acid methyl ester profiles were unique for each strain.
DL739T showed an ability to survive at 8 degrees C with little to no cellular
replication and is thus considered to be psychrotolerant. Therefore, strains
DL734T and DL739T represent two novel species of the genus Mycobacterium with the
proposed names Mycobacterium sarraceniae sp. nov. and Mycobacterium helvum sp.
nov., respectively. The type strains are DL734T (=JCM 30395T=NCCB 100519T) and
DL739T (=JCM 30396T=NCCB 100520T), respectively.
PMID- 27498538
TI - Mucilaginibacter puniceus sp. nov., isolated from wetland freshwater.
AB - A non-motile, rod-shaped and pale-pink bacterium, designated strain WS71T, was
isolated from freshwater collected from the Woopo Wetland (Republic of Korea).
Cells were Gram-stain-negative, aerobic, catalase-positive and oxidase-negative.
The major fatty acids were summed feature 3 (comprising C16 : 1omega6c and/or C16
: 1omega7c), iso-C17 : 0 3-OH, C16 : 0 and iso-C15 : 0. The strain contained
menaquinone 7 (MK-7) and the DNA G+C content was 39.4+/-0.4 mol%. The major polar
lipids were phosphatidylethanolamine and an unknown aminophospholipid. A
phylogenetic tree based on 16S rRNA gene sequences showed that WS71T forms an
evolutionary lineage within the radiation enclosing the members of genus
Mucilaginibacterwith Mucilaginibacter. soyangensis HME6664T as its nearest
neighbor (98.3 % sequence similarity). DNA-DNA relatedness between WS71T and M.
soyangensis HME6664T was 61.3+/-1.0 %. A number of phenotypic characteristics
distinguished WS71T from the other members of the genus Mucilaginibacter. On the
basis of the evidence presented in this study, WS71T represents a novel species,
for which the name Mucilaginibacterpuniceus sp. nov. is proposed. The type strain
is WS71T (=KCTC 32270T=JCM 19495T).
PMID- 27498539
TI - Vine nitrogen status and volatile thiols and their precursors from plot to
transcriptome level.
AB - BACKGROUND: Volatile thiols largely contribute to the organoleptic
characteristics and typicity of Sauvignon blanc wines. Among this family of
odorous compounds, 3-sulfanylhexan-1-ol (3SH) and 4-methyl-4-sulfanylpentan-2-one
(4MSP) have a major impact on wine flavor. These thiols are formed during
alcoholic fermentation by the yeast from odorless, non-volatile precursors found
in the berries and the must. The present study investigates the effects of vine
nitrogen (N) status on 3SH and 4MSP content in Sauvignon blanc wine and on the
glutathionylated and cysteinylated precursors of 3SH (Glut-3SH and Cys-3SH) in
the berries and the must. This is paralleled by a RNA-seq analysis of gene
expression in the berries. The impact of N supply on the expression of the
glutathione-S-transferase 3 and 4 (VviGST3 and VviGST4) and the gamma
glutamyltranspeptidase (VviGGT), considered as key genes in their biosynthesis,
was also evaluated. RESULTS: N supply (N100 treatment) increased the 3SH content
in wine while no effect was noticed on 4MSP level. Furthermore, N supply
increased Glut-3SH levels in grape berries at late berry ripening stages, and
this effect was highly significant in must at harvest. No significant effect of N
addition was noticed on Cys-3SH concentration. The transcript abundance of the
glutathione-S-transferases VviGST3 and VviGST4 and the gamma
glutamyltranspeptidase (VviGGT), were similar between the control and the N100
treatment. New candidate genes which might be implicated in the biosynthetic
pathway of 3SH precursors were identified by whole transcriptome shotgun
sequencing (RNA-seq). CONCLUSIONS: High vine N status has a positive effect on
3SH content in wine through an increase of Glut-3SH levels in grape berries and
must. Candidate GSTs and glutathione-S-conjugates type transporters involved in
this stimulation were identified by RNA-seq analysis.
PMID- 27498540
TI - Erratum to: ALG6-CDG: a recognizable phenotype with epilepsy, proximal muscle
weakness, ataxia and behavioral and limb anomalies.
PMID- 27498541
TI - Lactococcus garvieae subsp. bovis subsp. nov., lactic acid bacteria isolated from
wild gaur (Bos gaurus) dung, and description of Lactococcus garvieae subsp.
garvieae subsp. nov.
AB - A taxonomic investigation was performed on a Gram-stain-positive coccus,
designated strain BSN307T, isolated from gaur (Indian bison, Bos gaurus) dung
based on phenotypic and molecular approaches. Based on the biochemical tests,
cellular morphology and 16S rRNA gene sequence similarity, this strain was found
to be a member of the genus Lactococcus and closely related to Lactococcus
garvieae ATCC 49156T (99.6 % 16S rRNA gene sequence similarity) and L.actococcus
formosensis 516T (99.0 %). However, DNA-DNA hybridization studies showed that the
level of relatedness between strain BSN307T and L. garvieae ATCC 49156T was 75.8
%, suggesting that it represented a novel subspecies of L. garvieae. The
inability to grow in brain heart infusion (BHI) medium at pH 9.6, in tryptic soy
agar (TSA) with 4 % (w/v) NaCl and at 42 degrees C (MRS agar) clearly
differentiated BSN307T from L. garvieae ATCC 49156T. Rep-PCR fingerprint
patterns, substantial differences in summed feature 8 (C18 : 1omega7c/C18 :
1omega6c), C19 : 0 cyclo omega8c and C16 : 0 also differentiated strain BSN307T
from the reference strain of L. garvieae. Moreover, analysis of the housekeeping
genes pheS and rpoA revealed sequence similarities that were at the limit for
species differentiation (92.2 and 97.8 %, respectively). Combined genotypic and
phenotypic data indicate that strain BSN307T represents a subspecies of L.
garvieae for which the name Lactococcus garvieae subsp. bovis subsp. nov. is
proposed. The type strain is BSN307T (=DSM 100577 T=MCC 2824T=KCTC 21083T).
PMID- 27498542
TI - Lipoteichoic acids as a major virulence factor causing inflammatory responses via
Toll-like receptor 2.
AB - Lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria,
is associated with various inflammatory diseases ranging from minor skin diseases
to severe sepsis. It is known that LTA is recognized by Toll-like receptor 2
(TLR2), leading to the initiation of innate immune responses and further
development of adaptive immunity. However, excessive immune responses may result
in the inflammatory sequelae that are involved in severe diseases such as sepsis.
Although numerous studies have tried to identify the molecular basis for the
pathophysiology of Gram-positive bacterial infection, the exact role of LTA
during the infection has not been clearly elucidated. This review provides an
overview of LTA structure and host recognition by TLR2 that leads to the
activation of innate immune responses. Emphasis is placed on differential
immunostimulating activities of LTAs of various Gram-positive bacteria at the
molecular level.
PMID- 27498543
TI - Can IFNL3 polymorphisms predict response to interferon/ribavirin treatment in
hepatitis C patients with genotype 3?
AB - Favourable genotypes of IFNL3 polymorphism CC for rs12979860 and TT for rs8099917
are strongly associated with the interferon/ribavirin treatment outcome in
hepatitis C virus (HCV) patients with genotypes 1 and 4. Contrarily, conflicting
results have been reported for patients with HCV genotypes 2 and 3. Therefore, we
sought to investigate the association between IFNL3 with sustained virological
response (SVR) after treatment to ascertain the predictive value of IFNL3 single
nucleotide polymorphisms (SNPs) in HCV patients with genotype 3. For this
purpose, we genotyped five IFNL3 SNPs, rs12980275, rs12979860, rs9109886,
rs8099917 and rs7248668, in HCV patients with genotype 3 and assessed its
association with SVR, individually and in haplotype. Interestingly, we report
that the IFNL3 SNPs we genotyped have shown no association with SVR following
treatment, either individually or in haplotype, indicating that genotyping IFNL3
SNPs have limited predictive value in HCV patients with genotype 3. Therefore, we
propose that IFNL3 genotyping can be excluded from a patient's pre-treatment
workup for subsequent treatment choice. This will greatly reduce the economic
burden for HCV patients with genotype 3 in resource-limited regions, especially
South Asia where genotype 3 is predominant.
PMID- 27498544
TI - CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some
Subpopulations of Appendages: Comparison with Developing Fetal Skin.
AB - BACKGROUND: CD99 is a cell surface transmembrane glycoprotein expressed in
various tissues. CD99 is differentially expressed between subpopulations of each
tissue and is highly expressed in certain hematopoietic and precursor cells.
However, there has been no comprehensive study of CD99 expression in normal skin.
We evaluated CD99 expression in normal human skin and developing fetal skin.
METHODS: Seventy-five adult skin samples containing normal skin and eight fetal
skin samples of different gestational ages were collected. CD99
immunohistochemical staining was performed to evaluate expression pattern in
adult and fetal skin samples. CD99 and CD34 expression were compared by double
immunofluorescence. RESULTS: In normal adult skin, CD99 was strongly expressed in
the membrane of epidermal basal keratinocytes, hair follicle bulges and outer
root sheaths, and inner secretory cells of eccrine sweat glands. In fetal skin,
CD99 was not expressed on the periderm at 16 weeks of gestation but was expressed
in basal cells of fetal skin at around 19 weeks of gestation. CD99 expression
became comparable to that of the adult skin after 20 weeks of gestation. CD99 and
CD34 were co-expressed in hair follicle outer root sheaths, as seen by double
immunofluorescence study. CONCLUSIONS: This is the first study examining CD99
expression pattern in normal adult and fetal skin. CD99 tends to be expressed in
the basal/precursor cells of epidermis and in hair follicles. These results
provide a basis for future investigation on functions of CD99 in the skin and
provide a novel potential target for the treatment of dermatologic lesions.
PMID- 27498545
TI - Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma
and Urothelial Carcinoma.
AB - BACKGROUND: The pathologic distinction between high-grade prostate adenocarcinoma
(PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC)
infiltrating the prostate can be difficult. However, making this distinction is
clinically important because of the different treatment modalities for these two
entities. METHODS: A total of 249 patient cases (PAC, 111 cases; UC, 138 cases)
collected between June 1995 and July 2009 at Seoul St. Mary's Hospital were
studied. An immunohistochemical evaluation of prostatic markers (prostate
specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid
phosphatase [PAP], P501s, NKX3.1, and alpha-methylacyl coenzyme A racemase
[AMACR]) and urothelial markers (CK34betaE12, p63, thrombomodulin, S100P, and
GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each
tumor. RESULTS: The sensitivities of prostatic markers in PAC were 100% for PSA,
83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for
AMACR. However, the urothelial markers CK34betaE12, p63, thrombomodulin, S100P,
and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively.
The sensitivities of urothelial markers in UC were 75.4% for CK34betaE12, 73.9%
for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3.
Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were
also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively.
CONCLUSIONS: Prostatic and urothelial markers, including PSA, NKX3.1, p63,
thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The
optimal combination of prostatic and urothelial markers could improve the ability
to differentiate PAC from UC pathologically.
PMID- 27498546
TI - A Rare Case of Recurrent Metastatic Solid Pseudopapillary Neoplasm of the
Pancreas.
AB - A 61-year-old woman visited our hospital for bilateral multiple lung nodules and
a mass in her thorax. She had a long history of multiple metastatic recurrences
of solid pseudopapillary neoplasm (SPN); 24 years previously, the patient had
undergone pylorus-preserving pancreaticoduodenectomy for a 9.9 * 8.6 cm mass in
the pancreatic head. The tumor was diagnosed as an SPN. Nine years later,
metastatic nodules were found on computed tomography in the patient's liver and
peritoneum and were excised. She subsequently underwent an additional eight
metastatectomy procedures in diverse organs. For the presented event, the lung
nodules were removed. The prevalence of malignant SPN in the general population
is 5%-15%. However, multiple metastatic recurrence of malignant SPN is rare; the
lung is a particularly rare site of metastasis, found in only three cases in the
literature. Here, we describe this exceptional case and provide a literature
review.
PMID- 27498547
TI - Adult Intussusception Caused by Inverted Meckel's Diverticulum Containing
Mesenteric Heterotopic Pancreas and Smooth Muscle Bundles.
PMID- 27498548
TI - SIRT7, H3K18ac, and ELK4 Immunohistochemical Expression in Hepatocellular
Carcinoma.
AB - BACKGROUND: SIRT7 is one of the histone deacetylases and is NAD-dependent. It
forms a complex with ETS-like transcription factor 4 (ELK4), which deacetylates
H3K18ac and works as a transcriptional suppressor. Overexpression of SIRT7 and
deacetylation of H3K18ac have been shown to be associated with aggressive
clinical behavior in some cancers, including hepatocellular carcinoma (HCC). The
present study investigated the immunohistochemical expression of SIRT7, H3K18ac,
and ELK4 in hepatocellular carcinoma. METHODS: A total of 278 HCC patients were
enrolled in this study. Tissue microarray blocks were made from existing paraffin
embedded blocks. Immunohistochemical expressions of SIRT7, H3K18ac and ELK4 were
scored and analyzed. RESULTS: High SIRT7 (p = .034), high H3K18ac (p = .001), and
low ELK4 (p = .021) groups were associated with poor outcomes. Age < 65 years (p
= .028), tumor size >= 5 cm (p = .001), presence of vascular emboli (p = .003),
involvement of surgical margin (p = .001), and high American Joint Committee on
Cancer stage (III&V) (p < .001) were correlated with worse prognoses. In
multivariate analysis, H3K18ac (p = .001) and ELK4 (p = .015) were the
significant independent prognostic factors. CONCLUSIONS: High SIRT7 expression
with poor overall survival implies that deacetylation of H3K18ac contributes to
progression of HCC. High H3K18ac expression with poor prognosis is predicted due
to a compensation mechanism. In addition, high ELK4 expression with good
prognosis suggests another role of ELK4 as a tumor suppressor beyond SIRT7's
helper. In conclusion, we could assume that the H3K18ac deacetylation pathway is
influenced by many other factors.
PMID- 27498549
TI - Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck
Pain, Compared with a Pain Free Group-a Pilot Study.
AB - Objective: To test, in this pilot study, whether DHEA-S (Dehydroepiandrosterone,
sulfated form) plasma levels are lower among persons with chronic neck pain,
compared to control persons, and to investigate the DHEA-S response after a
physical exercise. Subjects: Included were 12 persons with chronic neck pain and
eight controls without present pain, all 18 and 65 years of age. Exclusion
criteria for both groups were articular diseases or tendinosis, fibromyalgia,
systemic inflammatory and neuromuscular diseases, pain conditions due to trauma,
or severe psychiatric diseases. Design and methods: The participants arm-cycled
on an ergometer for 30 minutes. Blood samples were taken before, 60 minutes, and
150 minutes after this standardized physical exercise. Results: The estimated
plasma DHEA-S levels at baseline were 2.0 umol/L (95% confidence interval [CI]
1.00; 4.01) in the pain group and 4.1 umol/L (95% CI2.0; 8.6) in the control
group, adjusted for sex, age, body mass index (BMI), and Shirom-Melamed Burnout
Questionnaire (SMBQ), with a ratio of 0.48 ( P = 0.094). Conclusions: In this
pilot study, the plasma DHEA-S levels appeared to be lower among the persons with
chronic neck pain, compared with the control group. It was indicated that DHEA-S
decreased during the physical exercise in the control group, and either increased
or was unaffected in the chronic pain group.
PMID- 27498550
TI - Developmental Validation of the Huaxia Platinum System and application in 3 main
ethnic groups of China.
AB - STRs, scattered throughout the genome with higher mutation rate, are attractive
to genetic application like forensic, anthropological and population genetics
studies. STR profiling has now been applied in various aspects of human
identification in forensic investigations. This work described the developmental
validation of a novel and universal assay, the Huaxia Platinum System, which
amplifies all markers in the expanded CODIS core loci and the Chinese National
Database in one single PCR system. Developmental validation demonstrated that
this novel assay is accurate, sensitive, reproducible and robust. No discordant
calls were observed between the Huaxia Platinum System and other STR systems.
Full genotypes could be achieved even with 250 pg of human DNA. Additionally, 402
unrelated individuals from 3 main ethnic groups of China (Han, Uygur and Tibetan)
were genotyped to investigate the effectiveness of this novel assay. The CMP were
2.3094 * 10(-27), 4.3791 * 10(-28) and 6.9118 * 10(-27), respectively, and the
CPE were 0.99999999939059, 0.99999999989653 and 0.99999999976386, respectively.
Aforementioned results suggested that the Huaxia Platinum System is polymorphic
and informative, which provides efficient tool for national DNA database and
facilitate international data sharing.
PMID- 27498551
TI - Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection
Following Adult Liver Transplantation.
AB - Discovery of non-invasive diagnostic and predictive biomarkers for acute
rejection in liver transplant patients would help to ensure the preservation of
liver function in the graft, eventually contributing to improved graft and
patient survival. We evaluated selected cytokines and chemokines in the sera from
liver transplant patients as potential biomarkers for acute rejection, and found
that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post
operation could predict acute rejection following adult liver transplantation
with 97% specificity and 94% sensitivity.
PMID- 27498552
TI - MicroRNA-27a Inhibits Cell Migration and Invasion of Fibroblast-Like Synoviocytes
by Targeting Follistatin-Like Protein 1 in Rheumatoid Arthritis.
AB - Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA)
are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies
have found that overexpression or silencing of miRNA can contribute to the
development of miRNA-based therapeutics in arthritis models. In this study, we
explored the effects of miR-27a on cell migration and invasion in cultured FLS
from RA patients. We found that miR-27a was markedly downregulated in the serum,
synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin
like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key
role in RA development. The results of a Transwell assay showed that miR-27a
inhibited FLS migration and invasion. However, miR-27a inhibition promoted the
migration and invasion of FLS. In addition, the down-regulated expression of
matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1,
Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by
quantitative reverse transcription-PCR and western blot analysis. Then, a
luciferase reporter assay validated that miR-27a targeted the 3-untranslated
region (3'-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of
FSTL1. In addition, the expression of TLR4 and NFkappaB was inhibited by miR-27a
but increased by FSTL1 overexpression. In conclusion, we found that miR-27a
inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and
restraining the TLR4/NFkappaB pathway.
PMID- 27498553
TI - Serum metabolomic signatures discriminate early liver inflammation and fibrosis
stages in patients with chronic hepatitis B.
AB - Chronic HBV (CHB) infected patients with intermediate necroinflammation and
fibrosis are recommended to receive antiviral treatment. However, other than
liver biopsy, there is a lack of sensitive and specific objective method to
determine the necroinflammation and fibrosis stages in CHB patients. This study
aims to identify unique serum metabolomic profile associated with histological
progression in CHB patients and to develop novel metabolite biomarker panels for
early CHB detection and stratification. A comprehensive metabolomic profiling
method was established to compare serum samples collected from health donor (n =
67), patients with mild (G < 2 and S < 2, CHB1, n = 52) or intermediate (G >= 2
or S >= 2, CHB2, n = 36) necroinflammation and fibrosis. Multivariate models were
developed to differentiate CHB1 and CHB2 from controls. A set of CHB-associated
biomarkers was identified, including lysophosphatidylcholines,
phosphatidylcholines, phosphatidylinositol, phosphatidylserine, and bile acid
metabolism products. Stratification of CHB1 and CHB2 patients by a simple
logistic index, the PIPSindex, based on phosphatidylinositol (PI) and
phosphatidylserine (PS), was achieved with an AUC of 0.961, which outperformed
all currently available markers. A panel of serum metabolites that differentiate
health control, CHB1 and CHB2 patients has been identified. The proposed
metabolomic biosignature has the potential to be used as indicator for antiviral
treatment for CHB management.
PMID- 27498555
TI - How should the post-2015 response to AIDS relate to the drive for universal
health coverage?
AB - The drive for universal health coverage (UHC) now has a great deal of normative
impetus, and in combination with the inauguration of the sustainable development
goals, has come to be regarded as a means of ensuring the financial basis for the
struggle against HIV and AIDS. The argument of this paper is that such thinking
is a case of 'the right thing at the wrong time': it seriously underestimates the
scale of the work against HIV and AIDS, and the speed with which we need to
undertake it, if we are to consolidate the gains we have made to date, let alone
reduce it to manageable proportions. The looming 'fiscal crunch' makes the
challenges all the more daunting; even in the best circumstances, the time
required to establish UHCs capable of providing both essential health services
and a very rapid scale-up of the fight against HIV and AIDS is insufficient when
set against the urgency of ensuring that AIDS does not eventuate as a global
health catastrophe.
PMID- 27498554
TI - Autophagy-associated alpha-arrestin signaling is required for conidiogenous cell
development in Magnaporthe oryzae.
AB - Conidiation patterning is evolutionarily complex and mechanism concerning
conidiogenous cell differentiation remains largely unknown. Magnaporthe oryzae
conidiates in a sympodial way and uses its conidia to infect host and disseminate
blast disease. Arrestins are multifunctional proteins that modulate receptor down
regulation and scaffold components of intracellular trafficking routes. We here
report an alpha-arrestin that regulates patterns of conidiation and contributes
to pathogenicity in M. oryzae. We show that disruption of ARRDC1 generates
mutants which produce conidia in an acropetal array and ARRDC1 significantly
affects expression profile of CCA1, a virulence-related transcription factor
required for conidiogenous cell differentiation. Although germ tubes normally
develop appressoria, penetration peg formation is dramatically impaired and
Deltaarrdc1 mutants are mostly nonpathogenic. Fluorescent analysis indicates that
EGFP-ARRDC1 puncta are well colocalized with DsRed2-Atg8, and this distribution
profile could not be altered in Deltaatg9 mutants, suggesting ARRDC1 enters into
autophagic flux before autophagosome maturation. We propose that M. oryzae
employs ARRDC1 to regulate specific receptors in response to conidiation-related
signals for conidiogenous cell differentiation and utilize autophagosomes for
desensitization of conidiogenous receptor, which transmits extracellular signal
to the downstream elements of transcription factors. Our investigation extends
novel significance of autophagy-associated alpha-arrestin signaling to fungal
parasites.
PMID- 27498556
TI - Interdependent IL-7 and IFN-gamma signalling in T-cell controls tumour
eradication by combined alpha-CTLA-4+alpha-PD-1 therapy.
AB - Combination therapy with alpha-CTLA-4 and alpha-PD-1 has shown significant
clinical responses in different types of cancer. However, the underlying
mechanisms remain elusive. Here, combining detailed analysis of human tumour
samples with preclinical tumour models, we report that concomitant blockade of
CTLA-4 and PD-1 improves anti-tumour immune responses and synergistically
eradicates tumour. Mechanistically, combination therapy relies on the
interdependence between IL-7 and IFN-gamma signalling in T cells, as lack of
either pathway abrogates the immune-boosting and therapeutic effects of
combination therapy. Combination treatment increases IL-7Ralpha expression on
tumour-infiltrating T cells in an IFN-gamma/IFN-gammaR signalling-dependent
manner, which may serve as a potential biomarker for clinical trials with immune
checkpoint blockade. Our data suggest that combining immune checkpoint blockade
with IL-7 signalling could be an effective modality to improve immunotherapeutic
efficacy. Taken together, we conclude that combination therapy potently reverses
immunosuppression and eradicates tumours via an intricate interplay between IFN
gamma/IFN-gammaR and IL-7/IL-7R pathways.
PMID- 27498557
TI - A novel recombinant cell fluorescence biosensor based on toxicity of pathway for
rapid and simple evaluation of DON and ZEN.
AB - During an exposure, humans and animals are most often exposed to a mixture rather
than individual mycotoxins. In this study, a Human Embryonic Kidney 293 cell (HEK
293) fluorescence sensor was developed to detect and evaluate mycotoxins,
deoxynivalenol (DON) and zearalenone (ZEN) compounds, produced by Fusarium
culmorum that are common food contaminants. TRE-copGFP (green fluorescent
protein) and ERE-TagRFP (red fluorescent protein) plasmids were constructed and
cotransfected into HEK-293 cells through a highly efficient, lipid-mediated, DNA
transfection procedure. Results show that fluorescence intensity was proportional
to DON and ZEN concentrations, ranging from 2 to 40 ng/mL and 10 to 100 ng/mL
respectively, with a detection limit of 0.75 ng/mL and 3.2 ng/mL respectively.
The EC50 of DON and ZEN are 30.13 ng/mL and 76.63 ng/mL respectively.
Additionally, ZEN may have a synergistic effect on enhancing AP-1 activity of the
toxicity pathway of DON. These data indicate the high sensitivity and
effectiveness of our biosensor system in the evaluation of the combined toxicity
of ZEN, DON and their derivatives. In addition, this approach is suitable for an
early warning method for the detection of ZEN and DON family mycotoxins
contamination without higher-priced, conventional analytical chemistry methods.
PMID- 27498559
TI - Effective Strategy for Colorimetric and Fluorescence Sensing of Phosgene Based on
Small Organic Dyes and Nanofiber Platforms.
AB - Three o-phenylendiamine (OPD) derivatives, containing 4-chloro-7
nitrobenzo[c][1,2,5]oxadiazole (NBD-OPD), rhodamine (RB-OPD), and 1,8
naphthalimide (NAP-OPD) moieties, were prepared and tested as phosgene
chemosensors. Unlike previously described methods to sense this toxic agent,
which rely on chemical processes that transform alcohols and amines to respective
phosphate esters and phosphoramides, the new sensors operate through a
benzimidazolone-forming reaction between their OPD groups and phosgene. These
processes promote either naked eye visible color changes and/or fluorescence
intensity enhancements in conjunction with detection limits that range from 0.7
to 2.8 ppb. NBD-OPD and RB-OPD-embedded polymer fibers, prepared using the
electrospinning technique, display distinct color and fluorescence changes upon
exposure to phosgene even in the solid state.
PMID- 27498558
TI - Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies.
AB - Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved
for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2
mutations. BRCA1- and BRCA2-mutated cells, which are homologous recombination
(HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic
lethality. Here we examine the effect of PARPi on HR-proficient cells. Olaparib
pretreatment, PARP1 knockdown or Parp1 heterozygosity of Brca2(cko/ko) mouse
embryonic stem cells (mESCs), carrying a null (ko) and a conditional (cko) allele
of Brca2, results in viable Brca2(ko/ko) cells. PARP1 deficiency does not restore
HR in Brca2(ko/ko) cells, but protects stalled replication forks from MRE11
mediated degradation through its impaired recruitment. The functional consequence
of Parp1 heterozygosity on BRCA2 loss is demonstrated by a significant increase
in tumorigenesis in Brca2(cko/cko) mice. Thus, while olaparib efficiently kills
BRCA2-deficient cells, we demonstrate that it can also contribute to the
synthetic viability if PARP is inhibited before BRCA2 loss.
PMID- 27498561
TI - Cross-Cultural Sex Differences in Post-Conflict Affiliation following Sports
Matches.
AB - The nature of ancestral human social structure and the circumstances in which men
or women tend to be more cooperative are subjects of intense debate. The male
warrior hypothesis proposes that success in intergroup contests has been vital in
human evolution and that men therefore must engage in maximally effective
intragroup cooperation [1-3]. Post-conflict affiliation between opponents is
further proposed to facilitate future cooperation [4], which has been
demonstrated in non-human primates [5] and humans [6]. The sex that invests more
in post-conflict affiliation, therefore, should cooperate more. Supportive
evidence comes from chimpanzees, a close genetic relative to humans that also
engages in male intergroup aggression [7]. Here we apply this principle to humans
by testing the hypothesis that among members of a large community, following a
conflict, males are predisposed to be more ready than females to repair their
relationship via friendly contact. We took high-level sports matches as a proxy
for intragroup conflict, because they occur within a large organization and
constitute semi-naturalistic, standardized, aggressive, and intense
confrontations. Duration or frequency of peaceful physical contacts served as the
measure of post-conflict affiliation because they are strongly associated with
pro-social intentions [8, 9]. Across tennis, table tennis, badminton, and boxing,
with participants from 44 countries, duration of post-conflict affiliation was
longer for males than females. Our results indicate that unrelated human males
are more predisposed than females to invest in a behavior, post-conflict
affiliation, that is expected to facilitate future intragroup cooperation.
PMID- 27498560
TI - Differentiation of malignant cervical lymphadenopathy by dual-energy CT: a
preliminary analysis.
AB - The accurate diagnosis of malignant cervical lymphadenopathy remains challenging.
In this study, we determined the value of quantitative parameters derived from
dual-energy computed tomography (DECT) for differentiating malignant cervical
lymphadenopathy caused by thyroid carcinoma (TC), salivary gland carcinoma (SC),
squamous cell carcinoma (SCC) and lymphoma. We retrospectively analysed 92
patients with pathologically confirmed cervical lymphadenopathy due to TC, SC,
SCC and lymphoma. All patients received a DECT scan before therapy. Using GSI
(gemstone spectral imaging) Volume Viewer software, we analysed the enhanced
monochromatic data, and the quantitative parameters we acquired included the
iodine concentration (IC), water concentration (WC) and the slope of the spectral
HU curve (lambdaHU). One-way ANOVA showed significant differences in the IC and
lambdaHU among different groups (P < 0.05). Post-hoc pairwise comparisons
demonstrated the IC and lambdaHU of TC group were significantly higher than those
of SC, SCC and lymphoma groups (P < 0.05). In addition, the IC and lambdaHU of SC
group were significantly higher than those of the SCC and lymphoma groups (P <
0.05). Other comparisons of IC and lambdaHU values showed no significant
differences (P > 0.05). The quantitative parameters derived from DECT were useful
supplements to conventional computed tomography images and were helpful for
distinguishing different malignant cervical lymphadenopathies.
PMID- 27498562
TI - Myosin Vc Is Specialized for Transport on a Secretory Superhighway.
AB - A hallmark of the well-studied vertebrate class Va myosin is its ability to take
multiple steps on actin as a single molecule without dissociating, a feature
called "processivity." Therefore, it was surprising when kinetic and single
molecule assays showed that human myosin Vc (MyoVc) was not processive on single
actin filaments [1-3]. We explored the possibility that MyoVc is processive only
under conditions that resemble its biological context. Recently, it was shown
that zymogen vesicles are transported on actin "superhighways" composed of
parallel actin cables nucleated by formins from the plasma membrane [4]. Loss of
these cables compromises orderly apical targeting of vesicles. MyoVc has been
implicated in transporting secretory vesicles to the apical membrane [5]. We
hypothesized that actin cables regulate the processive properties of MyoVc. We
show that MyoVc is unique in taking variable size steps, which are frequently in
the backward direction. Results obtained with chimeric constructs implicate the
lever arm/rod of MyoVc as being responsible for these properties. Actin bundles
allow single MyoVc motors to move processively. Remarkably, even teams of MyoVc
motors require actin bundles to move continuously at physiological ionic
strength. The irregular stepping pattern of MyoVc, which may result from
flexibility in the lever arm/rod of MyoVc, appears to be a unique structural
adaptation that allows the actin track to spatially restrict the activity of
MyoVc to specialized actin cables in order to co-ordinate and target the final
stages of vesicle secretion.
PMID- 27498563
TI - Wolbachia Protein TomO Targets nanos mRNA and Restores Germ Stem Cells in
Drosophila Sex-lethal Mutants.
AB - Wolbachia, endosymbiotic bacteria prevalent in invertebrates, manipulate their
hosts in a variety of ways: they induce cytoplasmic incompatibility, male
lethality, male-to-female transformation, and parthenogenesis. However, little is
known about the molecular basis for host manipulation by these bacteria. In
Drosophila melanogaster, Wolbachia infection makes otherwise sterile Sex-lethal
(Sxl) mutant females capable of producing mature eggs. Through a functional
genomic screen for Wolbachia genes with growth-inhibitory effects when expressed
in cultured Drosophila cells, we identified the gene WD1278 encoding a novel
protein we call toxic manipulator of oogenesis (TomO), which phenocopies some of
the Wolbachia effects in Sxl mutant D. melanogaster females. We demonstrate that
TomO enhances the maintenance of germ stem cells (GSCs) by elevating Nanos (Nos)
expression via its interaction with nos mRNA, ultimately leading to the
restoration of germ cell production in Sxl mutant females that are otherwise
without GSCs.
PMID- 27498564
TI - Glutamatergic Neurotransmission Links Sensitivity to Volatile Anesthetics with
Mitochondrial Function.
AB - An enigma of modern medicine has persisted for over 150 years. The mechanisms by
which volatile anesthetics (VAs) produce their effects (loss of consciousness,
analgesia, amnesia, and immobility) remain an unsolved mystery. Many attractive
putative molecular targets have failed to produce a significant effect when
genetically tested in whole-animal models [1-3]. However, mitochondrial defects
increase VA sensitivity in diverse organisms from nematodes to humans [4-6].
Ndufs4 knockout (KO) mice lack a subunit of mitochondrial complex I and are
strikingly hypersensitive to VAs yet resistant to the intravenous anesthetic
ketamine [7]. The change in VA sensitivity is the largest reported for a mammal.
Limiting NDUFS4 loss to a subset of glutamatergic neurons recapitulates the VA
hypersensitivity of Ndufs4(KO) mice, while loss in GABAergic or cholinergic
neurons does not. Baseline electrophysiologic function of CA1 pyramidal neurons
does not differ between Ndufs4(KO) and control mice. Isoflurane concentrations
that anesthetize only Ndufs4(KO) mice (0.6%) decreased the frequency of
spontaneous excitatory postsynaptic currents (sEPSCs) only in Ndufs4(KO) CA1
neurons, while concentrations effective in control mice (1.2%) decreased sEPSC
frequencies in both control and Ndufs4(KO) CA1 pyramidal cells. Spontaneous
inhibitory postsynaptic currents (sIPSCs) were not differentially affected
between genotypes. The effects of isoflurane were similar on evoked field
excitatory postsynaptic potentials (fEPSPs) and paired pulse facilitation (PPF)
in KO and control hippocampal slices. We propose that CA1 presynaptic excitatory
neurotransmission is hypersensitive to isoflurane in Ndufs4(KO) mice due to the
inhibition of pre-existing reduced complex I function, reaching a critical
reduction that can no longer meet metabolic demands.
PMID- 27498565
TI - Absence of Visual Input Results in the Disruption of Grid Cell Firing in the
Mouse.
AB - Grid cells are spatially modulated neurons within the medial entorhinal cortex
whose firing fields are arranged at the vertices of tessellating equilateral
triangles [1]. The exquisite periodicity of their firing has led to the
suggestion that they represent a path integration signal, tracking the organism's
position by integrating speed and direction of movement [2-10]. External sensory
inputs are required to reset any errors that the path integrator would inevitably
accumulate. Here we probe the nature of the external sensory inputs required to
sustain grid firing, by recording grid cells as mice explore familiar
environments in complete darkness. The absence of visual cues results in a
significant disruption of grid cell firing patterns, even when the quality of the
directional information provided by head direction cells is largely preserved.
Darkness alters the expression of velocity signaling within the entorhinal
cortex, with changes evident in grid cell firing rate and the local field
potential theta frequency. Short-term (<1.5 s) spike timing relationships between
grid cell pairs are preserved in the dark, indicating that network patterns of
excitatory and inhibitory coupling between grid cells exist independently of
visual input and of spatially periodic firing. However, we find no evidence of
preserved hexagonal symmetry in the spatial firing of single grid cells at
comparable short timescales. Taken together, these results demonstrate that
visual input is required to sustain grid cell periodicity and stability in mice
and suggest that grid cells in mice cannot perform accurate path integration in
the absence of reliable visual cues.
PMID- 27498566
TI - Neuromodulation of Courtship Drive through Tyramine-Responsive Neurons in the
Drosophila Brain.
AB - Neuromodulators influence the activities of collections of neurons and have
profound impacts on animal behavior. Male courtship drive is complex and subject
to neuromodulatory control. Using the fruit fly Drosophila melanogaster, we
identified neurons in the brain (inferior posterior slope; IPS) that impact
courtship drive and were controlled by tyramine-a biogenic amine related to
dopamine, whose roles in most animals are enigmatic. We knocked out a tyramine
specific receptor, TyrR, which was expressed in IPS neurons. Loss of TyrR led to
a striking elevation in courtship activity between males. This effect occurred
only in the absence of females, as TyrR(Gal4) mutant males exhibited a wild-type
preference for females. Artificial hyperactivation of IPS neurons caused a large
increase in male-male courtship, whereas suppression of IPS activity decreased
male-female courtship. We conclude that TyrR is a receptor for tyramine, and
suggest that it serves to curb high levels of courtship activity through
functioning as an inhibitory neuromodulator.
PMID- 27498568
TI - The Origin of High-Frequency Hearing in Whales.
AB - Odontocetes (toothed whales) rely upon echoes of their own vocalizations to
navigate and find prey underwater [1]. This sensory adaptation, known as
echolocation, operates most effectively when using high frequencies, and
odontocetes are rivaled only by bats in their ability to perceive ultrasonic
sound greater than 100 kHz [2]. Although features indicative of ultrasonic
hearing are present in the oldest known odontocetes [3], the significance of this
finding is limited by the methods employed and taxa sampled. In this report, we
describe a new xenorophid whale (Echovenator sandersi, gen. et sp. nov.) from the
Oligocene of South Carolina that, as a member of the most basal clade of
odontocetes, sheds considerable light on the evolution of ultrasonic hearing. By
placing high-resolution CT data from Echovenator sandersi, 2 hippos, and 23
fossil and extant whales in a phylogenetic context, we conclude that ultrasonic
hearing, albeit in a less specialized form, evolved at the base of the odontocete
radiation. Contrary to the hypothesis that odontocetes evolved from low-frequency
specialists [4], we find evidence that stem cetaceans, the archaeocetes, were
more sensitive to high-frequency sound than their terrestrial ancestors. This
indicates that selection for high-frequency hearing predates the emergence of
Odontoceti and the evolution of echolocation.
PMID- 27498567
TI - The Demographic Development of the First Farmers in Anatolia.
AB - The archaeological documentation of the development of sedentary farming
societies in Anatolia is not yet mirrored by a genetic understanding of the human
populations involved, in contrast to the spread of farming in Europe [1-3].
Sedentary farming communities emerged in parts of the Fertile Crescent during the
tenth millennium and early ninth millennium calibrated (cal) BC and had appeared
in central Anatolia by 8300 cal BC [4]. Farming spread into west Anatolia by the
early seventh millennium cal BC and quasi-synchronously into Europe, although the
timing and process of this movement remain unclear. Using genome sequence data
that we generated from nine central Anatolian Neolithic individuals, we studied
the transition period from early Aceramic (Pre-Pottery) to the later Pottery
Neolithic, when farming expanded west of the Fertile Crescent. We find that
genetic diversity in the earliest farmers was conspicuously low, on a par with
European foraging groups. With the advent of the Pottery Neolithic, genetic
variation within societies reached levels later found in early European farmers.
Our results confirm that the earliest Neolithic central Anatolians belonged to
the same gene pool as the first Neolithic migrants spreading into Europe.
Further, genetic affinities between later Anatolian farmers and fourth to third
millennium BC Chalcolithic south Europeans suggest an additional wave of
Anatolian migrants, after the initial Neolithic spread but before the Yamnaya
related migrations. We propose that the earliest farming societies
demographically resembled foragers and that only after regional gene flow and
rising heterogeneity did the farming population expansions into Europe occur.
PMID- 27498569
TI - Vision Guides Selection of Freeze or Flight Defense Strategies in Mice.
AB - In prey species such as mice, avoidance of predators is key to survival and
drives instinctual behaviors like freeze or flight [1, 2]. Sensory signals guide
the selection of appropriate behavior [3], and for aerial predators only vision
provides useful information. Surprisingly, there is no evidence that vision can
guide the selection of escape strategies. Fleeing behavior can be readily
triggered by a rapidly looming overhead stimulus [4]. Freezing behavior, however,
has previously been induced by real predators or their odors [5]. Here, we
discover that a small moving disk, simulating the sweep of a predator cruising
overhead, is sufficient to induce freezing response in mice. Looming and sweeping
therefore provide visual triggers for opposing flight and freeze behaviors and
provide evidence that mice innately make behavioral choices based on vision
alone. VIDEO ABSTRACT.
PMID- 27498570
TI - Endolysosomes Are the Principal Intracellular Sites of Acid Hydrolase Activity.
AB - The endocytic delivery of macromolecules from the mammalian cell surface for
degradation by lysosomal acid hydrolases requires traffic through early endosomes
to late endosomes followed by transient (kissing) or complete fusions between
late endosomes and lysosomes. Transient or complete fusion results in the
formation of endolysosomes, which are hybrid organelles from which lysosomes are
re-formed. We have used synthetic membrane-permeable cathepsin substrates, which
liberate fluorescent reporters upon proteolytic cleavage, as well as acid
phosphatase cytochemistry to identify which endocytic compartments are acid
hydrolase active. We found that endolysosomes are the principal organelles in
which acid hydrolase substrates are cleaved. Endolysosomes also accumulated
acidotropic probes and could be distinguished from terminal storage lysosomes,
which were acid hydrolase inactive and did not accumulate acidotropic probes.
Using live-cell microscopy, we have demonstrated that fusion events, which form
endolysosomes, precede the onset of acid hydrolase activity. By means of sucrose
and invertase uptake experiments, we have also shown that acid-hydrolase-active
endolysosomes and acid-hydrolase-inactive, terminal storage lysosomes exist in
dynamic equilibrium. We conclude that the terminal endocytic compartment is
composed of acid-hydrolase-active, acidic endolysosomes and acid hydrolase
inactive, non-acidic, terminal storage lysosomes, which are linked and function
in a lysosome regeneration cycle.
PMID- 27498571
TI - The impact of long working hours on psychosocial stress response among white
collar workers.
AB - This study examined the association between long working hours and psychosocial
stress responses. In total, 1,122 white-collar workers from a company in Korea
completed self-administered questionnaires following a lecture about the study
aim, procedures, and confidentiality. Psychosocial stress responses were
evaluated using the Psychosocial Well-being Index - Short Form (PWI-SF), and
psychosocial working conditions were evaluated with the Korean Occupational
Stress Scale - Short Form (KOSS-SF). Multivariate logistic regression analysis
was performed after adjusting for demographic variables and psychosocial working
conditions to examine associations between long working hours and psychosocial
stress responses. In comparison with the reference group, which worked 40-44
hours per week, the crude odds ratio (OR) of the respondents who worked 60 or
more hours was 4.56 (95% confidence interval (CI), 2.55-8.15) in terms of
psychosocial stress responses. After adjusting for demographic variables, the
adjusted OR of those working >=60 hours was 5.61 (95% CI, 3.01-10.47). After
adjusting for both demographic variables and psychosocial working conditions, the
adjusted OR of those working >=60 hours was 3.25 (95% CI, 1.56-6.79). This study
found that long working hours are significantly related to psychosocial stress
responses among white-collar workers in one Korean company.
PMID- 27498572
TI - Effects of an ergonomics-based job stress management program on job strain,
psychological distress, and blood cortisol among employees of a national private
bank in Denpasar Bali.
AB - The present work describes a newly developed ergonomics-based job stress
management program - Ergo-JSI (Ergonomics-based Job Stress Intervention) -
including a pilot study to ascertain the effects of the program on job strain,
psychological distress, and blood cortisol levels among bank employees in
Indonesia. A single-group, pre- and post-test experimental study was conducted in
a sample of employees in a National Bank in Denpasar, Bali, Indonesia. The
outcomes of the study focused on reductions in job strain index and psychological
distress, measured by the Indonesian version of the Brief Job Stress
Questionnaire (BJSQ), and improvement in blood cortisol levels following the
study.A total of 25 male employees, with an average age of 39, received an eight
week intervention with the Ergo-JSI. Compared to baseline, the job strain index
decreased by 46% (p<0.05), and psychological distress decreased by 28% (p<0.05).
These changes were accompanied by a 24% reduction in blood cortisol levels
(p<0.05). The newly developed Ergo-JSI program may hence be effective for
decreasing job strain, psychosocial distress, and blood cortisol among employees
in Indonesia.
PMID- 27498573
TI - Is age just a number: pancreaticoduodenectomy in elderly patients?
PMID- 27498574
TI - Dietary supplementation in patients with alcoholic liver disease: a review on
current evidence.
AB - BACKGROUND: Alcoholic liver disease (ALD) is one of the main causes of liver
disease worldwide. Although the pathogenesis of ALD has not yet been well
elucidated, the oxidative metabolites of ethanol such as acetaldehyde and
reactive oxygen species play a pivotal role in the clinical and pathological
spectrum of the disease. This review summarizes the existing evidences on dietary
supplements considered to have antioxidant, and/or anti-inflammatory properties,
and their role in the management of ALD and the proposed mechanisms. DATA
SOURCES: The present study reviewed all studies published in PubMed,
ScienceDirect and Scopus, from 1959 to 2015, indicating the role of different
dietary supplementation in attenuation of many pathophysiological processes
involved in development and progression of ALD. Full-texts of citations were used
except for those that were published in languages other than English. RESULTS:
Significant progress has been made to understand the key events and molecular
players for the onset and progression of ALD from both experimental and clinical
studies; however, there is no successful treatment currently available. The
present review discussed the role of a variety of dietary supplements (e.g.
vitamin A, carotenoids, vitamins B3, C and E, in addition to antioxidants and
anti-inflammatory agents) in treating ALD. It has been shown that supplementation
with some carotenoids, vitamin B3, vitamin C, silymarin, curcumin, probiotics,
zinc, S-adenosylmethionine and garlic may have potential beneficial effects in
animal models of ALD; however, the number of clinical studies is very limited. In
addition, supplementation should be accompanied with alcohol cessation.
CONCLUSIONS: Since oxidative stress and inflammation are involved in the
pathogenesis of ALD, dietary supplements that can modulate these pathologies
could be useful in the treatment of ALD. In addition to alcohol cessation, these
supplements have shown beneficial effects on animal models of ALD. Clinical
trials are needed to validate the beneficiary role of these supplements in
patients with ALD.
PMID- 27498575
TI - Advances in understanding the molecular mechanism of pancreatic cancer
metastasis.
AB - BACKGROUND: Pancreatic cancer (PC) is usually diagnosed at the late-stage and
therefore, has widespread metastasis and a very high mortality rate. The
mechanisms underlying PC metastasis are not well understood. Recent advances in
genomic sequencing have identified groups of gene mutations that affect PC
metastasis, but studies elucidating their roles are lacking. The present review
was to investigate the molecular mechanisms of PC metastasis. DATA SOURCES:
Relevant articles on PC metastasis were searched in MEDLINE via PubMed prior to
April 2015. The search was limited in English publications. RESULTS: PC
metastatic cascades are multi-factorial events including both intrinsic and
extrinsic elements. This review highlights the most important genetic alterations
and other mechanisms that account for PC invasion and metastasis, with particular
regard to epithelial-mesenchymal transition, inflammation, stress response, and
circulating tumor cells. CONCLUSIONS: Analyses of relevant gene functions and
signaling pathways are needed to establish the gene regulatory network and to
define the pivotal modulators. Another promising area of study is the genotyping
and phenotyping of circulating tumor cells, which could lead to a new era of
personalized therapy by identifying specific markers and targets.
PMID- 27498576
TI - Predictive value of tumor markers in patients with recurrent hepatocellular
carcinoma in different vascular invasion pattern.
AB - BACKGROUND: Four tumor markers for hepatocellular carcinoma (HCC), alpha
fetoprotein (AFP), glypican-3 (GPC3), vascular endothelial growth factor (VEGF)
and des-gamma-carboxy prothrombin (DCP), are closely associated with tumor
invasion and patient's survival. This study estimated the predictability of
preoperative tumor marker levels along with pathological parameters on HCC
recurrence after hepatectomy. METHODS: A total of 140 patients with HCC who
underwent hepatectomy between January 2012 and August 2012 were enrolled. The
demographics, clinical and follow-up data were collected and analyzed. The
patients were divided into two groups: patients with macroscopic vascular
invasion (MaVI+) and those without MaVI (MaVI-). The predictive value of tumor
markers and clinical parameters were evaluated by univariate and multivariate
analysis. RESULTS: In all patients, tumor size (>8 cm) and MaVI were closely
related to HCC recurrence after hepatectomy. For MaVI+ patients, VEGF (>900
pg/mL) was a significant predictor for recurrence (RR=2.421; 95% CI: 1.272-4.606;
P=0.007). The 1- and 2-year tumor-free survival rates for MaVI+ patients with
VEGF <=900 pg/mL versus for those with VEGF >900 pg/mL were 51.5% and 17.6%
versus 19.0% and 4.8% (P<0.001). For MaVI- patients, DCP >445 mAu/mL and tumor
size >8 cm were two independent risk factors for tumor recurrence (RR=2.307, 95%
CI: 1.132-4.703, P=0.021; RR=3.150, 95% CI: 1.392-7.127, P=0.006; respectively).
The 1- and 2-year tumor-free survival rates for the patients with DCP <=445
mAu/mL and those with DCP >445 mAu/mL were 90.4% and 70.7% versus 73.2% and 50.5%
respectively (P=0.048). The 1- and 2-year tumor-free survival rates for the
patients with tumor size <=8 cm and >8 cm were 83.2% and 62.1% versus 50.0% and
30.0%, respectively (P=0.003). CONCLUSIONS: The MaVI+ patients with VEGF <=900
pg/mL had a relatively high tumor-free survival than those with VEGF >900 pg/mL.
In the MaVI- patients, DCP >445 mAu/mL and tumor size >8 cm were predictive
factors for postoperative recurrence.
PMID- 27498577
TI - Combined hepatectomy and radiofrequency ablation versus TACE in improving
survival of patients with unresectable BCLC stage B HCC.
AB - BACKGROUND: Combined hepatectomy and radiofrequency ablation (RFA) provides an
additional treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage
B hepatocellular carcinoma (HCC) who are conventionally deemed unresectable. This
study aimed to analyze the outcome of this combination therapy by comparing it
with transarterial chemoembolization (TACE). METHODS: We retrospectively reviewed
51 patients with unresectable BCLC stage B HCC who had received the combination
therapy. We compared the survival of these patients with that of 102 patients in
the TACE group (control). Prognostic factors associated with worse survival in
the combination group were analyzed. RESULTS: No differences in tumor status and
liver function were observed between the TACE group and combination group. The
median survival time for the combination group and TACE group was 38 (6-54) and
17 (3-48) months, respectively (P<0.001). The combination group required longer
hospitalization than the TACE group [8 (5-14) days vs 4 (2-9) days, P<0.001].
More than two ablations decreased the survival rate in the combination group.
CONCLUSIONS: Combined hepatectomy and RFA yielded a better long-term outcome than
TACE in patients with unresectable BCLC stage B HCC. Patients with a limited
ablated size (<=2 cm), a limited number of ablations (<=2), and adequate surgical
margin should be considered candidates for combination therapy.
PMID- 27498578
TI - Indocyanine green retention is a potential prognostic indicator after splenectomy
and pericardial devascularization for cirrhotic patients.
AB - BACKGROUND: Splenectomy and pericardial devascularization (SPD) is an effective
treatment of upper gastrointestinal bleeding and hypersplenism in cirrhotic
patients with portal hypertension. Indocyanine green retention at 15 minutes
(ICGR15) was reported to offer better sensitivity and specificity than the Child
Pugh classification in hepatectomy, but few reports describe ICGR15 in SPD. The
present study was to evaluate the prognostic value of ICGR15 for cirrhotic
patients with portal hypertension who underwent SPD. METHODS: From January 2012
to January 2015, 43 patients with portal hypertension and hypersplenism caused by
liver cirrhosis were admitted in our center and received SPD. The ICGR15, Child
Pugh classification, model for end-stage liver disease (MELD) score, and
perioperative characteristics were analyzed retrospectively. RESULTS:
Preoperative liver function assessment revealed that 34 patients were Child-Pugh
class A with ICGR15 of 13.6%-43.0% and MELD score of 7-20; 8 patients were class
B with ICGR15 of 22.8%-40.7% and MELD score of 7-17; 1 patient was class C with
ICGR15 of 39.7% and MELD score of 22. The optimal ICGR15 threshold for liver
function compensation was 31.2%, which offered a sensitivity of 68.4% and a
specificity of 70.8%. Univariate analysis showed preoperative ICGR15, MELD score,
surgical procedure, intraoperative blood loss, and autologous blood transfusion
were significantly different between postoperative liver function compensated and
decompensated groups. Multivariate regression analysis revealed that ICGR15 was
an independent risk factor of postoperative liver function recovery (P=0.020).
CONCLUSIONS: ICGR15 has outperformed the Child-Pugh classification for assessing
liver function in cirrhotic patients with portal hypertension. ICGR15 may be a
suitable prognostic indicator for cirrhotic patients after SPD.
PMID- 27498579
TI - Differentiation of pyogenic hepatic abscesses from malignant mimickers using
multislice-based texture acquired from contrast-enhanced computed tomography.
AB - BACKGROUND: Pyogenic hepatic abscess may mimic primary or secondary carcinoma of
the liver on contrast-enhanced computed tomography (CECT). The present study was
to explore the usefulness of the analysis of multislice-based texture acquired
from CECT in the differentiation between pyogenic hepatic abscesses and malignant
mimickers. METHODS: This retrospective study included 25 abscesses in 20 patients
and 33 tumors in 26 subjects who underwent CECT. To make comparison, we also
enrolled 19 patients with hepatic single simple cyst. The images from CECT were
analyzed using a Laplacian of Gaussian band-pass filter (5 filter levels with
sigma weighting ranging from 1.0 to 2.5). We also quantified the uniformity,
entropy, kurtosis and skewness of the multislice-based texture at different sigma
weightings. Statistical significance for these parameters was tested with one-way
ANOVA followed by Tukey honestly significant difference (HSD) test. Diagnostic
performance was evaluated using the receiver operating characteristic (ROC) curve
analysis. RESULTS: There were significant differences in entropy and uniformity
at all sigma weightings (P<0.001) among hepatic abscesses, malignant mimickers
and simple cysts. The significant difference in kurtosis and skewness was shown
at sigma 1.8 and 2.0 weightings (P=0.002-0.006). Tukey HSD test showed that the
abscesses had a significantly higher entropy and lower uniformity compared with
malignant mimickers (P=0.000-0.004). Entropy (at a sigma 2.0 weighting) had the
largest area under the ROC curve (0.888) in differentiating abscesses from
malignant mimickers, with a sensitivity of 81.8% and a specificity of 88.0% when
the cutoff value was set to 3.64. CONCLUSION: Multislice-based texture analysis
may be useful for differentiating pyogenic hepatic abscesses from malignant
mimickers.
PMID- 27498580
TI - Effects of Salmonella infection on hepatic damage following acute liver injury in
rats.
AB - BACKGROUND: Acute liver injury is a common clinical disorder associated with
intestinal barrier injury and disturbance of intestinal microbiota. Probiotic
supplementation has been reported to reduce liver injury; however, it is unclear
whether enteropathogen infection exacerbates liver injury. The purpose of this
study was to address this unanswered question using a rat model. METHODS: Oral
supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was
given to rats for 7 days. Different degrees of acute liver injury were then
induced by intraperitoneal injection of D-galactosamine. The presence and extent
of liver injury was assayed by measuring the concentrations of serum alanine
aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was
used to observe liver tissue damage. Additionally, we measured the changes in
plasma endotoxin, serum cytokines and bacterial translocation to clarify the
mechanisms underlying intestinal microbiota associated liver injury. RESULTS: The
levels of liver damage and endotoxin were significantly increased in the
Salmonella infected rats with severe liver injury compared with the no infection
rats with severe liver injury (P<0.01); The peyer's patch CD3+ T cell counts were
increased significantly when the Salmonella infection with severe injury group
was compared with the normal group (P<0.05). S. enteritidis pretreatment enhanced
intestinal barrier impairment and bacterial translocation. CONCLUSIONS: Oral S.
enteritidis administration exacerbates acute liver injury, especially when injury
was severe. Major factors of the exacerbation include inflammatory and oxidative
stress injuries induced by the translocated bacteria and associated endotoxins,
as well as over-activation of the immune system in the intestine and liver.
PMID- 27498581
TI - Bio-compatibility and cytotoxicity studies of water-soluble CuInS2-ZnS-AFP
fluorescence probe in liver cancer cells.
AB - BACKGROUND: The oncogenesis of hepatocellular carcinoma (HCC) is not clear. The
current methods of the pertinent studies are not precise and sensitive. The
present study was to use liver cancer cell line to explore the bio-compatibility
and cytotoxicity of ternary quantum dots (QDs) probe and to evaluate the possible
application of QDs in HCC. METHODS: CuInS2-ZnS-AFP fluorescence probe was
designed and synthesized to label the liver cancer cell HepG2. The cytotoxicity
of CuInS2-ZnS-AFP probe was evaluated by MTT experiments and flow cytometry.
RESULTS: The labeling experiments indicated that CuInS2-ZnS QDs conjugated with
AFP antibody could enter HepG2 cells effectively and emit intensive yellow
fluorescence by ultraviolet excitation without changing cellular morphology.
Toxicity tests suggested that the cytotoxicity of CuInS2-ZnS-AFP probe was
significantly lower than that of CdTe-ZnS-AFP probe (t test, F=0.8, T=-69.326,
P<0.001). For CuInS2-ZnS-AFP probe, time-effect relationship was presented in
intermediate concentration (>20%) groups (P<0.05) and dose-effect relationship
was presented in almost all of the groups (P<0.05). CONCLUSION: CuInS2-ZnS-AFP
QDs probe had better bio-compatibility and lower cytotoxicity compared with CdTe
ZnS-AFP probe, and could be used for imaging the living cells in vitro.
PMID- 27498582
TI - Long-term follow-up of children and adolescents with primary sclerosing
cholangitis and autoimmune sclerosing cholangitis.
AB - BACKGROUND: Sclerosing cholangitis (SC) is a chronic cholestatic hepatobiliary
disease with uncertain long-term prognosis in pediatric patients. This study
aimed to evaluate long-term results in children with SC according to the types of
SC. METHODS: We retrospectively followed up 25 children with SC over a period of
4-17 years (median 12). The diagnosis of SC was based on biochemical,
histological and cholangiographic findings. Patients fulfilling diagnostic
criteria for probable or definite autoimmune hepatitis at the time of diagnosis
were defined as having autoimmune sclerosing cholangitis (ASC); other patients
were included in a group of primary sclerosing cholangitis (PSC). The incidence
of the following complications was studied: obstructive cholangitis, portal
hypertension, advanced liver disease and death associated with the primary
disease. RESULTS: Fourteen (56%) patients had PSC and 11 (44%) had ASC. Patients
with ASC were significantly younger at the time of diagnosis (12.3 vs 15.4 years,
P=0.032) and had higher IgG levels (22.7 vs 17.2 g/L, P=0.003). The mentioned
complications occurred in 4 (16%) patients with SC, exclusively in the PSC group:
one patient died from colorectal cancer, one patient underwent liver
transplantation and two patients, in whom severe bile duct stenosis was present
at diagnosis, were endoscopically treated for acute cholangitis. Furthermore, two
other children with ASC and 2 children with PSC had elevated aminotransferase
levels. The 10-year overall survival was 95.8% in all patients, 100% in patients
without complicated liver disease, and 75.0% in patients with complications.
CONCLUSION: In children, ASC is a frequent type of SC, whose prognosis may be
better than that in patients with PSC.
PMID- 27498583
TI - Outcomes of pancreaticoduodenectomy in elderly patients.
AB - BACKGROUND: Although the mortality and morbidity of pancreaticoduodenectomy (PD)
have improved significantly over the past years, the concerns for elderly
patients undergoing PD are still present. Furthermore, the frequency of PD is
increasing because of the increasing proportion of elderly patients and the
increasing incidence of periampullary tumors. This study aimed to analyze the
outcomes of PD in elderly patients. METHODS: We studied all patients who had
undergone PD in our center between January 1995 and February 2015. The patients
were divided into three groups based on age: group I (patients aged <60 years),
group II (those aged 60 to 69 years) and group III (those aged >=70 years). The
primary outcome was the rate of total postoperative complications. Secondary
endpoint included total operative time, hospital mortality, length of
postoperative hospital stay, delayed gastric emptying, re-exploration, and
survival rate. RESULTS: A total of 828 patients who had undergone PD for
resection of periampullary tumor were included in this study. There were 579
(69.9%) patients in group I, 201 (24.3%) in group II, and 48 (5.8%) in group III.
The overall incidence of complications was higher in elderly patients (25.9% in
group I, 36.8% in group II, and 37.5% in group III; P=0.006). There were more
patients complicated with delayed gastric emptying in group II compared with the
other two groups. There was no significant difference in the incidence of
postoperative pancreatic fistula, biliary leakage, pancreatitis, pulmonary
complications and hospital mortality. CONCLUSIONS: PD can be performed safely in
selected elderly patients. Advanced age alone should not be a contraindication
for PD. The outcome of elderly patients who have undergone PD is similar to that
of younger patients, and the increased rate of complications is due to the
presence of associated comorbidities.
PMID- 27498584
TI - Risk factors of infected pancreatic necrosis secondary to severe acute
pancreatitis.
AB - BACKGROUND: Severe acute pancreatitis (SAP) remains a clinical challenge with
considerable morbidity and mortality. An early identification of infected
pancreatic necrosis (IPN), a life-threatening evolution secondary to SAP, is
obliged for a more preferable prognosis. Thus, the present study was conducted to
identify the risk factors of IPN secondary to SAP. METHODS: The clinical data of
patients with SAP were retrospectively analyzed. Univariate and multivariate
logistic regression analyses were sequentially performed to assess the
associations between the variables and the development of IPN secondary to SAP. A
receiver operating characteristic (ROC) curve was created for each of the
qualified independent risk factors. RESULTS: Of the 115 eligible patients, 39
(33.9%) progressed to IPN, and the overall in-hospital mortality was 11.3%
(13/115). The early enteral nutrition (EEN) (P=0.0092, OR=0.264), maximum intra
abdominal pressure (IAP) (P=0.0398, OR=1.131) and maximum D-dimer level
(P=0.0001, OR=1.006) in the first three consecutive days were independent risk
factors associated with IPN secondary to SAP. The area under ROC curve (AUC) was
0.774 for the maximum D-dimer level in the first three consecutive days and the
sensitivity was 90% and the specificity was 58% at a cut-off value of 933.5
MUg/L; the AUC was 0.831 for the maximum IAP in the first three consecutive days
and the sensitivity was 95% and specificity was 58% at a cut-off value of 13.5
mmHg. CONCLUSIONS: The present study suggested that the maximum D-dimer level
and/or maximum IAP in the first three consecutive days after admission were risk
factors of IPN secondary to SAP; an EEN might be helpful to prevent the
progression of IPN secondary to SAP.
PMID- 27498585
TI - Pancreatitis in pregnancy: etiology, diagnosis, treatment, and outcomes.
AB - BACKGROUND: Acute pancreatitis in pregnancy is a rare and dangerous disease. This
study aimed to examine the etiology, treatment, and outcomes of pancreatitis in
pregnancy. METHOD: A total of 25 pregnant patients diagnosed with pancreatitis
during the period of 1994 and 2014 was analyzed retrospectively. RESULTS: The
pregnant patients were diagnosed with pancreatitis during a period of 21 years.
Most (60%) of the patients were diagnosed with pancreatitis in the third
trimester. The mean age of the patients at presentation was 25.7 years, with a
mean gestational age of 24.4 weeks. Abdominal pain occurred in most patients and
vomiting in one patient was associated hyperemesis gravidarum. The common cause
of the disease was gallstone-related (56%), followed by alcohol-related (16%),
post-ERCP (4%), hereditary (4%) and undetermined conditions (20%). The level of
triglycerides was minimally high in three patients. ERCP and wire-guided
sphincterotomy were performed in 6 (43%) of 14 patients with gallstone-related
pancreatitis and elevated liver enzymes with no complications. Most (84%) of the
patients underwent a full-term, vaginal delivery. There was no difference in
either maternal or fetal outcomes after ERCP. CONCLUSIONS: Acute pancreatitis is
rare in pregnancy, occurring most commonly in the third trimester, and gallstones
are the most common cause. When laparoscopic cholecystectomy is not feasible and
a common bile duct stone is highly suspected on imaging, endoscopic
sphincterotomy or stenting may help to prevent recurrence and postpone
cholecystectomy until after delivery.
PMID- 27498586
TI - Kidney transplantation after liver transplantation.
AB - Kidney transplantation after liver transplantation (KALT) offers longer survival
and a better quality of life to liver transplantation recipients who develop
chronic renal failure. This article aimed to discuss the efficacy and safety of
KALT compared with other treatments. The medical records of 5 patients who had
undergone KALT were retrospectively studied, together with a literature review of
studies. Three of them developed chronic renal failure after liver
transplantation because of calcineurin inhibitor (CNI)-induced nephrotoxicity,
while the others had lupus nephritis or non-CNI drug-induced nephrotoxicity. No
mortality was observed in the 5 patients. Three KALT cases showed good prognoses,
maintaining a normal serum creatinine level during entire follow-up period.
Chronic rejection occurred in the other two patients, and a kidney graft was
removed from one of them. Our data suggested that KALT is a good alternative to
dialysis for liver transplantation recipients. The cases also indicate that KALT
can be performed with good long-term survival.
PMID- 27498587
TI - Type 2 diabetes, high blood pressure and acute pancreatitis.
PMID- 27498588
TI - Implication of genomic characterization in synchronous endometrial and ovarian
cancers of endometrioid histology.
AB - OBJECTIVES: Synchronous endometrial and ovarian carcinomas (SEOCs) present
gynecologic oncologists with a challenging diagnostic puzzle: discriminating
between double primary cancers and single primary cancer with metastasis. We
aimed to determine the clonal relationship between simultaneously diagnosed
endometrial and ovarian carcinomas. METHODS: Fourteen pairs of SEOCs of
endometrioid type and two pairs of SEOCs with disparate histologic types (control
for dual primary tumors) were subjected to massively parallel sequencing (MPS)
and molecular inversion probe microarrays. RESULTS: Thirteen of the 14 pairs of
SEOCs harbored somatic mutations shared by both uterine and ovarian lesions,
indicative of clonality. High degree of chromosomal instability in the tumors
from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous
carcinomas with significantly overlapping copy number alterations (CNAs),
suggestive of single primary tumors with metastasis. The clonal relationship
determined by genomic analyses did not agree with clinicopathological criteria in
11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial
carcinomas in 4 patients, who did not receive adjuvant chemotherapy and
experienced no recurrent diseases. In contrast, two of the 10 patients with
chromosomally unstable cancers developed recurrent tumors. CONCLUSION: Our
findings support a recent paradigm-shifting concept that most SEOCs originate
from a single tumor. It also casts doubt on the clinicopathological criteria used
to distinguish between dual primary tumors and single primary tumor with
metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant
therapy.
PMID- 27498589
TI - Comprehensive evaluation of liver microsomal cytochrome P450 3A (CYP3A)
inhibition: comparison of cynomolgus monkey and human.
AB - 1. Members of the cytochrome P450 3A (CYP3A) subfamily metabolize numerous
compounds and serve as the loci of drug-drug interactions (DDIs). Because of high
amino acid sequence identity with human CYP3A, the cynomolgus monkey has been
proposed as a model species to support DDI risk assessment. 2. Therefore, the
objective of this study was to evaluate 35 known inhibitors of human CYP3A using
human (HLM) and cynomolgus monkey (CLM) liver microsomes. Midazolam was employed
as substrate to generate IC50 values (concentration of inhibitor rendering 50%
inhibition) in the absence and presence of a preincubation (30 mins) with NADPH.
3. In the absence of preincubation, the IC50 values generated with CLM were
similar to those obtained with HLM (86% within 2-fold; 100% within 3-fold
difference). However, significant differences (up to 48-fold) in preincubation
IC50 were observed with 17% of the compounds (raloxifene, bergamottin,
nicardipine, mibefradil, ritonavir, and diltiazem). 4. Our results indicate that
in most cases the cynomolgus monkey can be a viable DDI model. However,
significant species differences in time-dependent CYP3A inhibition can be
observed for some compounds. In the case of raloxifene, such a difference can be
ascribed to a specific CYP3A4 amino acid residue.
PMID- 27498590
TI - Effective cleavage of phosphodiester promoted by the zinc(II) and copper(II)
inclusion complexes of beta-cyclodextrin.
AB - To construct the model of metallohydrolase, two inclusion complexes [MLCl2(beta
CD)] (1, M=Zn(II); 2, M=Cu(II); L=N,N'-bis(2-pyridylmethyl)amantadine; beta
CD=beta-cyclodextrin) were synthesized by mixing beta-CDs with the pre
synthesized complexes G1, [ZnLCl2] and G2, [CuLCl2]. Structures of G1, G2, 1 and
2 were characterized by X-ray crystallography, respectively. In solution, two
chloride anions of G1 and G2 underwent ligand exchange with solvent molecules
according to ESI-MS analysis. The chemical equilibrium constants were determined
by potentiometric pH titration. The kinetics of bis(4-nitrophenyl) phosphate
(BNPP) hydrolysis catalyzed by G1, G2, 1 and 2 were examined at pHs ranging from
7.50 to 10.50 at 308+/-0.1K. The pH profile of rate constant of BNPP hydrolysis
catalyzed by 1 exhibited an exponential increase with the second-order rate
constant of 2.68*10-3M-1s-1 assigned to the di-hydroxo species, which was
approximately an order of magnitude higher than those of reported mono-Zn(II)
hydroxo species. The high reactivity was presumably hydroxyl-rich
microenvironment provided by beta-CDs, which might effect in stabilizing either
the labile zinc-hydroxo species or the catalytic transition state.
PMID- 27498592
TI - Hexaarylbenzene: Evolution of Properties and Applications of Multitalented
Scaffold.
AB - The easily rotatable peripheral aromatic rings around central benzene in
hexaarylbenzene (HAB) derivatives create a very intriguing nonplanar, propeller
shaped geometry. Because of the very low susceptibility toward self-aggregation,
HAB derivatives are much stronger candidates among various polyphenylenes/hetero
oligophenylenes when poor molecular cohesion and inefficient packing is required.
However, the native properties of hexaphenylbenzene (HPB) can be varied by proper
tailoring and substitution of the HAB core. The cohesion and packing in the
structures of HAB aggregates induce effective structural variations so as to
modify the fundamental features. Recently, HAB derivatives attracted a lot of
research interest because of their significant role as liquid crystalline
materials, organic light-emitting diodes, photochemical switches, redox
materials, and molecular receptors. Herein, detailed attention is given to the
pioneering work based on synthetic optimization of different HAB cores,
elaborated study of their crystal engineering, various interesting applications
of HAB derivatives, and future possibilities and capabilities of this still
underexplored scaffold.
PMID- 27498593
TI - Globular-disorder transition in proteins: a compromise between hydrophobic and
electrostatic interactions?
AB - The charge-hydrophobicity correlation of globular and disordered proteins is
explored using a generalized self-consistent field theoretical method combined
with Monte Carlo simulations. Globular and disordered protein sequences with
varied mean net charge and mean hydrophobicity are designed by theory, while
Metropolis Monte Carlo generates a suitable ensemble of conformations. Results
imply a transition of the dominant interactions between globular and disordered
proteins across the charge-hydrophobicity boundary. It is observed that the
charge-hydrophobicity boundary actually represents a trade-off between the
repulsive and attractive interactions in a protein sequence. The attractive
interactions predominate on the globular side of the boundary, while the
repulsive interactions prevail on the disordered side. For globular proteins,
core forming hydrophobic interactions are dominant leading to a minimally
frustrated native conformation. For disordered proteins, the repulsive
electrostatic interactions prevail yielding a minimally frustrated region
comprising of an expanded, dynamic conformational ensemble. Thus, protein
disorder, like protein folding, satisfies the principle of minimal frustration.
All results are compared to real globular and disordered proteins. Thus this
algorithm may be useful to probe the conformational characteristics of disordered
proteins.
PMID- 27498591
TI - Use of ferrous iron by metallo-beta-lactamases.
AB - Metallo-beta-lactamases (MBLs) catalyse the hydrolysis of almost all beta-lactam
antibacterials including the latest generation carbapenems and are a growing
worldwide clinical problem. It is proposed that MBLs employ one or two zinc ion
cofactors in vivo. Isolated MBLs are reported to use transition metal ions other
than zinc, including copper, cadmium and manganese, with iron ions being a
notable exception. We report kinetic and biophysical studies with the di-iron(II)
substituted metallo-beta-lactamase II from Bacillus cereus (di-Fe(II) BcII) and
the clinically relevant B1 subclass Verona integron-encoded metallo-beta
lactamase 2 (di-Fe(II) VIM-2). The results reveal that MBLs can employ ferrous
iron in catalysis, but with altered kinetic and inhibition profiles compared to
the zinc enzymes. A crystal structure of di-Fe(II) BcII reveals only small
overall changes in the active site compared to the di-Zn(II) enzyme including
retention of the di-metal bridging water; however, the positions of the metal
ions are altered in the di-Fe(II) compared to the di-Zn(II) structure. Stopped
flow analyses reveal that the mechanism of nitrocefin hydrolysis by both di
Fe(II) BcII and di-Fe(II) VIM-2 is altered compared to the di-Zn(II) enzymes.
Notably, given that the MBLs are the subject of current medicinal chemistry
efforts, the results raise the possibility the Fe(II)-substituted MBLs may be of
clinical relevance under conditions of low zinc availability, and reveal
potential variation in inhibitor activity against the differently metallated
MBLs.
PMID- 27498594
TI - Incompatibility between fasting and postprandial plasma glucose in patients with
Cushing's syndrome.
AB - It is shown that glucocorticoids have discordant effects on plasma glucose
concentration through their effects on hepatic glycogen deposition,
gluconeogenesis and peripheral insulin resistance. Cushing's syndrome caused by
cortisol overproduction is frequently accompanied with diabetes mellitus, but
fasting plasma glucose (FPG) and post-glucose load plasma glucose levels are not
examined in patients with Cushing's syndrome. The aim of this study was to
investigate FPG, HbA1c and oral glucose tolerance test (OGTT) 2-h PG and their
relationship in patients with Cushing's syndrome, in comparison with control
subjects. Sixteen patients with Cushing's syndrome (ACTH-dependent 31%, ACTH
independent 69% and diabetes mellitus 50%) and 64 controls (32 patients with type
2 diabetes mellitus and 32 non-diabetic subjects matched for age, sex and BMI)
were enrolled in this study. HbA1c and FPG in the patients with Cushing's
syndrome were not different from the controls, whereas the FPG/HbA1c ratio was
significantly lower in the patients with Cushing's syndrome than the controls.
OGTT 2-h PG was significantly higher in the non-diabetic patients with Cushing's
syndrome than the non-diabetic controls, while HbA1c was not different between
both groups and FPG was significantly lower in the patients with Cushing's
syndrome than the controls. HOMA-beta but not HOMA-R was significantly higher in
the patients with Cushing's syndrome than the controls. In conclusion, FPG was
rather lower in the patients with Cushing's syndrome than the controls.
Postprandial PG or post-glucose loaded PG, but not FPG, is useful to evaluate the
abnormality of glucose metabolism in patients with Cushing's syndrome.
PMID- 27498595
TI - Early safety and efficacy outcomes of a novel technique of sacrocolpopexy for the
treatment of apical prolapse.
AB - OBJECTIVE: To assess the safety and efficacy of a modified technique of bilateral
abdominal sacrocolpopexy in which both uterosacral ligaments are replaced with
polyvinylidene fluoride mesh to provide support to the cervix (cervico-sacropexy
[CESA]) or vaginal vault (vagino-sacropexy [VASA]). METHODS: A retrospective
observational study was undertaken of women with posthysterectomy vault prolapse
or recurrent apical prolapse following previous prolapse repair who underwent
bilateral sacrocolpopexy between July 1, 2013, and December 31, 2014, in a
tertiary referral unit in the UK. Before surgery and 3 months afterwards,
prolapse was assessed using the Pelvic Organ Prolapse Quantification scale and
functional outcomes were recorded using the International Consultation on
Incontinence Questionnaire for vaginal symptoms and urinary incontinence.
RESULTS: Fifty women were included. At 3 months, 47 (94%) patients reported no
bulge symptoms and the mean point C was -7.6. Complications comprised bladder
injury in 1 (2%) and minor wound problems in 3 (6%) patients. No mesh erosion was
reported. CONCLUSION: Bilateral abdominal sacrocolpopexy seems to be a safe and
effective option for apical prolapse. Longer-term follow-up is needed to detect
prolapse recurrence and mesh-related complications.
PMID- 27498596
TI - Breast reconstruction in older patients: A literature review of the decision
making process.
AB - AIM: Women not undergoing breast reconstruction after mastectomy tend to be
older. This review aims to aid in effective, evidence-based choices regarding
breast reconstruction in an older population, appraising the influencing patient
factors described in the literature and those directing the reconstructive
surgeon. This may refute current misconceptions and ensure surgical decisions are
made based on evidence without ageist assumptions. The review forms the basis of
an evidence-based algorithm addressing each step of the decision-making process.
METHOD: A literature search was conducted using PubMed, Medline, Evidence.nhs.uk
and the Cochrane database. Search terms initially were breast reconstruction,
mastectomy, elderly, older, decision, reasons and rationale. A separate
literature search was performed for each of the individual 'steps' in the
decision-making process. RESULTS: Overall, 44 papers were obtained. For each
section of the decision-making process, titles and abstracts were screened for
relevance. Only English language papers were included. CONCLUSION: If
reconstruction is oncologically plausible and co-morbidities and frailty formally
assessed, older women should be actively informed about breast reconstruction,
receive support and engage in 'shared decision-making'. The older patient is less
likely to do research independently. Amongst other factors, body image, cancer
fears, employment and carer responsibilities play a part in the decision. With
adequate preoperative and frailty assessment and early involvement of the
geriatrician and anaesthetist, microsurgical reconstruction is safe. Autologous
reconstruction has better long-term outcomes than implant-based reconstructions
in this age group, correlating with improved survival and longevity of
reconstruction. Age alone should not be considered a contraindication to breast
reconstruction.
PMID- 27498597
TI - Fucoidan inhibits angiogenesis induced by multiple myeloma cells.
AB - Multiple myeloma (MM) remains an incurable hematological neoplasms. Our previous
studies showed that Fucoidan possessed anti-myeloma effect by inducing apoptosis
and inhibiting invasion of myeloma cells. In this study, we evaluated the effect
of Fucoidan on angiogenesis induced by human myeloma cells and elucidated its
possible mechanisms. Multiple myeloma cells were treated with Fucoidan at
different concentrations, then the conditioned medium (CM) was collected. The
levels of VEGF in the CM were tested by ELISA. The results showed that Fucoidan
significantly decreased VEGF secretion by RPMI-8226 and U266 cells. The tube
formation assay and migration test on human umbilical vein endothelial cells
(HUVECs) were used to examine the effect of Fucoidan on angiogenesis induced by
human myeloma cells. The results showed that Fucoidan decreased HUVECs formed
tube structures and inhibited HUVECs migration, and suppressed the angiogenic
ability of multiple myeloma RPMI-8226 and U266 cells in a dose-dependent manner.
The study also showed that Fucoidan downregulated the expression of several kinds
of proteins, which may be correlated with the reduction of angiogenesis induced
by myeloma cells. Moreover, results were compared from normoxic and hypoxic
conditions, they showed that Fucoidan had anti-angiogenic activity. Furthermore,
in a multiple myeloma xenograft mouse model, it indicated that Fucoidan
negatively affected tumor growth and angiogenesis in vivo. In conclusion, our
results demonstrate that Fucoidan was able to interfere with angiogenesis of
multiple myeloma cells both in vitro and in vivo and may have a substantial
potential in the treatment of MM.
PMID- 27498598
TI - Re: Efficacy of High-intensity Local Treatment for Metastatic Urothelial
Carcinoma of the Bladder: A Propensity Score-Weighted Analysis from the National
Cancer Data Base.
PMID- 27498599
TI - Familial Associations Between Prostate Cancer and Other Cancers.
AB - : Prostate cancer (PCa) has a large familial component, but understanding of its
genetic basis is fragmentary. Breast cancers may be associated with PCa, but
whether this is true for other tumor types is poorly established. We used a novel
approach to study familial associations of any type of cancer with PCa. We
assessed the relative risk (RR) for all types of tumors as a function of the
number of first-degree relatives diagnosed with PCa. We hypothesized that for a
familial association to be real, the RR for a given type of cancer should
increase with the number of PCa diagnoses. In families with multiple PCa
patients, significantly increased risks were observed for female breast cancer
(RR 1.37 for families with three men with PCa), kidney cancer (RR 2.32), nervous
system tumors (RR 1.77; RR 2.40 when PCa was diagnosed before age 70 yr), and
myeloma (RR 2.44; RR 6.29 when PCa was diagnosed before age 70 yr). Some evidence
of association was also found for melanoma (RR 1.82) and endocrine tumors (RR
2.18). The consistency and magnitude of the effects suggest that familial PCa is
genetically associated with breast, kidney, and nervous system tumors and
myeloma. This suggestion has implications for clinical counseling and design of
genetic studies. PATIENT SUMMARY: It is known that prostate cancer runs in
families, but it is not known whether other cancers are common in such families.
We showed that at least breast, kidney, and nervous system tumors and myeloma
occur more often than by chance.
PMID- 27498600
TI - Neuroprotective effects of caffeic acid phenethyl ester against sevoflurane
induced neuronal degeneration in the hippocampus of neonatal rats involve MAPK
and PI3K/Akt signaling pathways.
AB - Millions of infants and children are exposed to anesthesia every year during
medical care. Sevoflurane is a volatile anesthetic that is frequently used for
pediatric anesthesia. However, previous reports have suggested that the
administration of sevoflurane promotes neurodegeneration, raising concerns
regarding the safety of its usage. The present study aimed to investigate caffeic
acid phenethyl ester (CAPE) and its protective effect against sevoflurane-induced
neurotoxicity in neonatal rats. Rat pups were administered with CAPE at 10, 20 or
40 mg/kg body weight from postnatal day 1 (P1) to P15. The P7 rats were exposed
to sevoflurane (2.9%) for 6 h. Control group rats received no sevoflurane or
CAPE. Neuronal apoptosis was determined by terminal deoxynucleotidyl transferase
dUTP nick-end labeling assay. The expression levels of caspases (caspase-3, -8
and -9), apoptotic pathway proteins [Bcl-2-associated X protein (Bax), B cell
CCL/lymphoma 2 (Bcl-2), Bcl-2-like 1 (Bcl-xL), Bcl-2-associated agonist of cell
death (Bad) and phosphorylated (p)-Bad], mitogen-activated protein kinases (MAPK)
signaling pathway proteins [c-Jun N-terminal kinase (JNK), p-JNK, extracellular
signal-regulated kinase (ERK)1/2, p-ERK1/2, p38, p-p38 and p-c-Jun] and the
phosphoinositide 3-kinase (PI3K)/Akt cascade were evaluated by western blotting
following sevoflurane and CAPE treatment. In addition, the expression of cleaved
caspase-3 was analyzed by immunohistochemistry. CAPE significantly reduced
sevoflurane-induced apoptosis, downregulated the expression levels of caspases
and pro-apoptotic proteins (Bax and Bad) and elevated the expression levels of
Bcl-2 and Bcl-xL when compared with sevoflurane treatment. Furthermore, CAPE
appeared to modify the expression levels of MAPKs and activate the PI3K/Akt
signaling pathway. Thus, the present study demonstrated that CAPE effectively
inhibited sevoflurane-induced neuroapoptosis by modulating the expression and
phosphorylation of apoptotic pathway proteins and MAPKs, and by regulating the
PI3K/Akt pathway.
PMID- 27498601
TI - Sustained Impact of an Antibiotic Stewardship Intervention for Community-Acquired
Pneumonia.
AB - Antibiotic stewardship interventions targeting community-acquired pneumonia have
been successful in reducing antibiotic overuse in the short term, but the
sustainability of their effects has not been investigated. We report that
improvements in antibiotic use due to a syndrome-focused intervention for
community-acquired pneumonia were sustained 3 years later without additional
intervention. Infect Control Hosp Epidemiol 2016;1-4.
PMID- 27498602
TI - Choroidal and Retinal Thickness in Children With Different Refractive Status
Measured by Swept-Source Optical Coherence Tomography.
PMID- 27498603
TI - Right to property, inheritance, and contract and persons with mental illness.
AB - Discrimination against people with mental illness is rife across the globe. Among
different types of discrimination is the policy in many countries where persons
with mental illness are forbidden to inherit property, and they are not able to
enter into a contract in a large number of countries. Using various databases,
legislations dealing with law of contract, law of succession/inheritance, and law
relating to testamentary capacity (wills) of all UN Member states (193 countries)
were studied. With respect to federal countries, the laws of the most populous
state as a representative state in the respective country were studied. Only 40
Member States (21%) recognize/allow persons with mental health problems to enter
into contracts. Of these, however, only 16 Member States (9%) recognize the right
of persons with mental health problems to enter into a contract without any
restrictions. The remaining 24 Member States (12%) allow a contract entered into
by a person with mental health problems to be invalidated under certain
conditions. These countries also make the validity of the contract subject to the
capacity to consent or based on the level of understanding of the person with
mental health problems. They may allow persons with mental health problems to
enter into contracts only for transactions of an insignificant nature or of
personal rights. Only 9% of the countries allow people with mental illness to
enter into contracts in an unrestricted way. Furthermore, there remain variations
between high income and low income states. In spite of international laws in many
countries, laws remain discriminatory.
PMID- 27498605
TI - The Ti-Mn system revisited: experimental investigation and thermodynamic
modelling.
AB - As the Ti-Mn phase diagram is part of numerous ternary and higher order systems
of technological importance, the present paper defines phase relations which have
been experimentally established throughout this work from 800 degrees C to the
melting range based on Differential Thermal Analyses (DTA), X-ray powder
diffraction, metallography and Electron Probe Micro Analysis (EPMA) techniques on
~50 alloys, which were prepared by arc melting or high frequency melting under
high purity argon starting from freshly cleaned metal ingots. Novel compounds
were identified and reaction isotherms were redefined accordingly. In the Ti-rich
region a novel compound TiMn was detected, sandwiched between the known phases:
TiMn1-x (~45 at% Mn) and TiMn1+x (~55 at% Mn). In the Mn-rich region the hitherto
unknown crystal structure of TiMn~3 was solved from X-ray single crystal
diffraction data and found to be of a unique structure type Ti6(Ti1-xMnx)6Mn25 (x
= 0.462; space group Pbam (#55); a = 0.79081(3) nm, b = 2.58557(9) nm, c =
0.47931(2) nm), which consists of two consecutive layers of the hexagonal MgZn2
type Laves phase (TiMn2) and a combined layer of alternate structure blocks of
MgZn2 type and Zr4Al3 type. Whereas TiMn can be considered as a line compound
(solubility range <~1 at%), the homogeneity regions of the Ti-Mn compounds are
significant (determined by EPMA): TiMn1-x (44.0 to 46.6 at% Mn), TiMn1+x (54.6 to
56.3 at% Mn), Ti1+xMn2-x (MgZn2-type, 59 to 69 at% Mn at 1000 degrees C: -0.08 <
x < 0.23), TiMn~3 (unique type; 74 to 76.5 at% Mn) and TiMn~4 (R-phase:
Ti8(TixMn1-x)6Mn39, 80 to 84 at% Ti). Supported by ab initio calculations of the
ground state energy for the Laves phase, the new experimental results enabled
thermodynamic modelling of the entire Ti-Mn phase diagram providing a complete
and novel set of thermodynamic data thus providing a sound basis for future
thermodynamic predictions of higher order Ti-Mn-X-Y systems.
PMID- 27498606
TI - Long-Term Effects of Repeated Prefrontal Cortex Transcranial Direct Current
Stimulation (tDCS) on Food Craving in Normal and Overweight Young Adults.
AB - BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) plays an important role in
the regulation of food intake. Several previous studies demonstrated that a
single session of transcranial direct current stimulation (tDCS) of the DLPFC
reduces food craving and caloric intake. OBJECTIVES: We hypothesized that
repeated tDCS of the right DLPFC cortex may exert long-term changes in food
craving in young, healthy adults and that these changes may differ between normal
and overweight subjects. METHODS: Thirty healthy individuals who reported
frequent food cravings without a prior history of eating disorders were initially
recruited. Subjects were randomized into an ACTIVE group who received 5 days of
real tDCS (20 minutes, anode right-cathode left montage, 2 mA with current
density kept at 0.06 mA/cm2, 1 min ramp-up/ramp-down), and a SHAM group, who
received one day of real tDCS, on the first day (same parameters), followed by 4
days of sham tDCS. Food craving intensity was examined by Food Craving
Questionnaires State and Trait and Food Craving Inventory before, during, (5
days) and one month (30-days) after tDCS. RESULTS: Single session of tDCS
significantly reduced the intensity of current food craving (FCQ-S). Five days of
active tDCS significantly reduced habitual experiences of food craving (FCQ-T),
when compared to baseline pre-stimulation levels. Furthermore, both current (FCQ
S) and habitual craving (FCQ-T) were significantly reduced 30 days after active
tDCS, while sham tDCS, i.e. a single tDCS session did not have significant
effects. Also, active tDCS significantly decreased craving for fast food and
sweets, and to a lesser degree for fat, while it did not have significant effects
on craving for carbohydrates (FCI). There were no significant differences between
individual FCQ-T subscales (craving dimensions) after 5 or 30 days of either sham
or active tDCS. Changes in craving were not significantly associated with the
initial weight, or with weight changes 30 days after the stimulation in the
subjects. CONCLUSIONS: The results confirm earlier findings that single session
of tDCS has immediate effects in reducing food craving. They also show that
repeated tDCS over the right DLPFC may increase the duration of its effects,
which may be present 30 days after the stimulation. These results support further
investigation of the use of tDCS in obesity.
PMID- 27498604
TI - Cytokine decoy and scavenger receptors as key regulators of immunity and
inflammation.
AB - IL-1R2 was the first decoy receptor to be described. Subsequently receptors which
act as pure decoys or scavengers or trigger dampening of cytokine signaling have
been described for cytokines and chemokines. Here we review the current
understanding of the mode of action and significance in pathology of the
chemokine atypical receptor ACKR2, the IL-1 decoy receptor IL-1R2 and the
atypical IL-1 receptor family IL-1R8. Decoy and scavenger receptors with no or
atypical signaling have emerged as a general strategy conserved in evolution to
tune the action of cytokines, chemokines and growth factors.
PMID- 27498607
TI - Enhanced gas separation factors of microporous polymer constrained in the
channels of anodic alumina membranes.
AB - New composite membranes based on porous anodic alumina films and polymer of
intrinsic microporosity (PIM-1) have been prepared using a spin-coating
technique. According to scanning electron microscopy, partial penetration of
polymer into the pores of alumina supports takes place giving rise to selective
polymeric layers with fiber-like microstructure. Geometric confinement of rigid
PIM-1 in the channels of anodic alumina causes reduction of small-scale mobility
in polymeric chains. As a result, transport of permanent gases, such as CH4,
becomes significantly hindered across composite membranes. Contrary, the
transport of condensable gases (CO2, S4H10), did not significantly suffer from
the confinement due to high solubility in the polymer matrix. This strategy
enables enhancement of selectivity towards CO2 and C4H10 without significant loss
of the membrane performance and seems to be prospective for drain and sweetening
of natural gas.
PMID- 27498609
TI - Stability and reactivity control of carbenoids: recent advances and perspectives.
AB - Metal carbenoids such as lithium or Simmons-Smith-type reagents are widely used
in organic synthesis, particularly in cyclopropanation and homologation
reactions. These reagents are often highly reactive and thermally labile, thus
limiting their isolation and hampering the development of new synthetic
applications. Recent years however, have shown that by means of systematic
stabilization a control of reactivity and the development of new applications is
possible. This feature article documents recent developments in the control of
carbenoid reactivity and stability and highlights structural and electronic
properties as well as applications in main group element and transition metal
chemistry.
PMID- 27498608
TI - Structure-function aspects of the Porphyromonas gingivalis tyrosine kinase Ptk1.
AB - The development of synergistically pathogenic communities of Porphyromonas
gingivalis and Streptococcus gordonii is controlled by a tyrosine-phosphorylation
dependent signaling pathway in P. gingivalis. The Ptk1 bacterial tyrosine (BY)
kinase of P. gingivalis is required for maximal community development and for the
production of extracellular polysaccharide. We show that the consensus BY kinase
Walker A and B domains, the RK cluster, and the YC domain of Ptk1 are necessary
for autophosphorylation and for substrate phosphorylation. Mass spectrometry
showed that six tyrosine residues in a 16-amino-acid C-terminal region were
phosphorylated in recombinant (r) Ptk1. Complementation of a ptk1 mutant with the
wild-type ptk1 allele in trans restored community development between P.
gingivalis and S. gordonii, and extracellular polysaccharide production by P.
gingivalis. In contrast, complementation of Deltaptk1 with ptk1 containing a
mutation in the Walker A domain failed to restore community development or
extracellular polysaccharide production. rPtk1 was capable of phosphorylating the
tyrosine phosphatase Ltp1 and the transcriptional regulator CdhR, both of which
are involved in the development of P. gingivalis communities with S. gordonii.
PMID- 27498611
TI - Fluoroquinolone resistance of Streptococcus pneumoniae isolates causing invasive
disease: special focus on zabofloxacin.
AB - The present study examined the in vitro activity of various antibiotics including
zabofloxacin, against isolates responsible for invasive pneumococcal diseases.
Between 1997 and 2008, a total of 208 isolates were collected from sterile
fluids, including blood (n=196, 94.2%), pleural fluid (n=5, 2.4%), cerebrospinal
fluid (n=5, 2.4%), and ascites (n=2, 1.0%). Zabofloxacin showed the lowest MIC50
(0.015MUg/mL) and MIC90 (0.025MUg/mL) values of all the tested antibiotics. Rates
of isolates resistant to penicillin (MIC >=8MUg/mL), ceftriaxone (MIC >=4MUg/mL)
and levofloxacin (MIC >=8MUg/mL) were 3.4%, 0.4% and 2.0%, respectively. Four
isolates (2.0%) were resistant to levofloxacin, and zabofloxacin showed low MICs
(range, 0.025-0.125MUg/mL). Zabofloxacin shows potent in vitro activity against
S. pneumoniae isolates that caused invasive disease, even strains that are
resistant to levofloxacin.
PMID- 27498610
TI - Population structure of invasive Streptococcus pneumoniae isolates among Alaskan
children in the conjugate vaccine era, 2001 to 2013.
AB - Here we describe the relationships between serotypes, genotypes, and
antimicrobial susceptibility among isolates causing invasive pneumococcal disease
in Alaskan children during the pneumococcal conjugate vaccine (PCV) era. From
2001 to 2013 we received 271 isolates representing 33 serotypes. The most common
serotypes were 19A (29.5%, n= 80), 7F (12.5%, n= 34), 15B/C (6.3%, n= 17), and
22F (4.8%, n= 13). Multilocus sequence typing identified 11 clonal complexes (CC)
and 45 singletons. Five CCs accounted for 52% (141/271) of the total: CC199 (21%
[n= 57], serotypes 19A, 15B/C), CC191 (12.2% [n= 33], serotype 7F), CC172 (10.3%
[n= 28], serotypes 19A, 23A, 23B), CC433 (4.4% [n= 12], serotype 22F), and CC100
(4.4% [n= 12], serotype 33F). The proportion of isolates nonsusceptible to
erythromycin and tetracycline increased after 13-valent PCV use (14% [n= 30]
versus 29% [n= 14]; P= 0.010) and (4% [n= 9] versus 22% [n= 11]; P< 0.001),
respectively. The genetic diversity also increased after 13-valent PCV use
(Simpson's diversity index =0.95 versus 0.91; P= 0.022).
PMID- 27498612
TI - Elevated progesterone on the trigger day does not impair the outcome of Human
Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles.
AB - To demonstrate the incidence and effects of elevated progesterone (P) on the
trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm
injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with
Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective
analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the
P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between
1.5-2 ng/mL (including 1.5), and >=2 ng/mL. The primary outcome measure was live
birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92%
(120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5
2 ng/mL, and >=2 ng/mL, respectively. The mean stimulation duration, total hMG
dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day
and the number of oocytes in patients with elevated P were significantly higher
than patients with P < 1 ng/mL (P < 0.05). However, there were no significant
differences in the oocyte retrieval rates, fertilization rates, implantation
rates, clinical pregnancy rates and live birth rates between the groups based on
frozen embryo transfer (FET). We concluded that elevated P on the trigger day had
no negative effect on the final outcome of the hMG + MPA treatment cycles based
on FET.
PMID- 27498613
TI - Incorporating structure context of HA protein to improve antigenicity calculation
for influenza virus A/H3N2.
AB - The rapid and consistent mutation of influenza requires frequent evaluation of
antigenicity variation among newly emerged strains, during which several in
silico methods have been reported to facilitate the assays. In this paper, we
designed a structure-based antigenicity scoring model instead of those sequence
based previously published. Protein structural context was adopted to derive the
antigenicity-dominant positions, as well as the physic-chemical change of local
micro-environment in correlation with antigenicity change. Then a position
specific scoring matrix (PSSM) profile and local environmental change over above
positions were integrated to predict the antigenicity variance. Independent
testing showed a high accuracy of 0.875, and sensitivity of 0.986, with a
significant ability to discover antigenic-escaping strains. When applying this
model to the historical data, global and regional antigenic drift events can be
successfully detected. Furthermore, two well-known vaccine failure events were
clearly suggested. Therefore, this structure-context model may be particularly
useful to identify those to-be-failed vaccine strains, in addition to suggest
potential new vaccine strains.
PMID- 27498614
TI - First-principles analysis on role of spinel (111) phase boundaries in
Li4+3xTi5O12 Li-ion battery anodes.
AB - The practical anode material Li4+3xTi5O12 is known to undergo a two-phase
separation into Li7Ti5O12 and Li4Ti5O12 during charging/discharging. This phase
separated Li4+3xTi5O12 exhibits electron conduction, although individual phases
are expected to be insulators. To elucidate the role played by spinel (111) phase
boundaries on these physical properties, first principles calculations were
carried out using the GGA+U method. Two-phase Li7Ti5O12/Li4Ti5O12 models are
found to exhibit metallic characteristics near their phase boundaries. These
boundaries provide conduction paths not only for electrons, but also for Li ions.
Judging from the formation energy of Li vacancies/interstitials, the phase
boundaries preferentially uptake or release Li via in-plane conduction and then
continuously shift in a direction perpendicular to the phase boundary planes. The
continuous phase boundary shift leads to a constant electrode potential. A three
dimensional network of cubic {111} planes may contribute to smooth
electrochemical reactions.
PMID- 27498615
TI - A new quinolinone from freshwater lake-derived fungus Myrothecium verrucaria.
AB - One new quinolinone, 7-hydroxy-3-methoxyviridicatin (1), along with eight known
compounds (2-9) was isolated from the fungus Myrothecium verrucaria, which was
collected from lake water of Chenghai, Yunnan Province, China. Their structures
were elucidated by detailed analysis of spectroscopic data and comparison with
related known compounds. Compounds 1 and 2 exhibited weak antibacterial activity.
To the best of our knowledge, this is the first report on quinolinones (1-4) as
the secondary metabolites of M. verrucaria.
PMID- 27498616
TI - The Culprit Is in the Cave: The Core Sites Explain the Binding Profiles of
Amyloid-Specific Tracers.
AB - The design of molecular probes and tracer molecules with specificity toward
amyloid beta (Abeta) fibrils is of paramount importance for the selective
diagnosis of Alzheimer's disease. This requires a detailed understanding of the
binding sites in amyloid targets, their number, and their binding mechanism for
various tracer molecules. We adopt an integrated approach including molecular
docking, molecular dynamics, and generalized Born-based free energy calculations
to investigate site-specific interactions of different amyloid binding molecules.
Our study reproduces the experimental results on the relative binding affinity of
the tracers and amyloid binders and explains the feature of "multiple binding
sites" in amyloid targets as probed by competition binding experiments. A major
outcome of this study is that it is the core sites of the Abeta fibrils that are
responsible for the experimentally reported binding profiles of tracers in
amyloid targets rather than the surface sites that received much focus in earlier
investigations.
PMID- 27498617
TI - Paragonimus westermani infection mimicking recurrent lung cancer: A case report.
AB - Herein, we report a case of Paragonimus westermani infection, which required
differentiation from recurrent lung cancer. A 66-year old Japanese man with a
history of lung cancer who had undergone a lobectomy was referred to our clinic
for treatment of cough, sputum, dyspnea, and a right pulmonary nodule. He had
previously eaten seafood he visited China. P. westermani infection was confirmed
by the presence of antibody against P. westermani antigen in the patient's serum
and eggs in his sputum. Eventually, molecular identification by PCR-restriction
fragment length polymorphism analysis and sequencing confirmed that the patient
was infected with triploid forms of P. westermani.
PMID- 27498618
TI - Development of a Method for the N-Arylation of Amino Acid Esters with Aryl
Triflates.
AB - A general method for the N-arylation of amino acid esters with aryl triflates is
described. Both alpha- and beta-amino acid esters, including methyl, tert-butyl,
and benzyl esters, are viable substrates. Reaction optimization was carried out
by design of experiment (DOE) analysis using JMP software. The mild reaction
conditions, which use t-BuBrettPhos Pd G3 or G4 precatalyst, result in minimal
racemization of the amino acid ester. This method is the first synthetic
application of the t-BuBrettPhos Pd G4 precatalyst. Mechanistic studies show that
the observed erosion in enantiomeric excess is due to racemization of the amino
acid ester starting material and not of the product.
PMID- 27498620
TI - Transcriptional regulation of E-cadherin by small activating RNA: A new double
stranded RNA.
AB - Recent studies have reported that chemically synthesized small activating RNA
(saRNA) targeting the promoter regions of a gene can activate its expression in
different cell lines. This technique can be a powerful therapeutic method for
diseases caused by complete inactivation or reduced expression of specific genes.
E-cadherin is a typical tumor suppressor gene. Loss of E-cadherin mediates the
transition from benign lesions to invasive, metastatic cancer. In this study,
several 21-nt small double-stranded RNAs (dsRNAs) targeting the promoter regions
of human E-cadherin were designed and synthesized and the features of their
function were investigated to study the regulatory role of dsRNA on E-cadherin
expression. A new saRNA (dsEcad-661) that can enhance E-cadherin expression by
targeting non-coding regulatory regions in gene promoters was identified. Using
dsRNA with modified base quantity and cholesterol-conjugated dsRNA, we found the
antisense strand may be the guide strand of saRNA in the upregulation of E
cadherin. These findings provide several important pieces of evidence that may
improve understanding of the function of saRNA and may promote its development
for clinical application.
PMID- 27498619
TI - Identification of uterine leiomyoma-specific marker genes based on DNA
methylation and their clinical application.
AB - Differential diagnosis of uterine leiomyomas and leiomyosarcomas is needed to
determine whether the uterus can be retained. Therefore, biomarkers for uterine
leiomyomas, and reliable and objective diagnostic methods have been desired
besides the pathological diagnosis. In the present study, we identified 12 genes
specific to uterine leiomyomas based on DNA methylation. Using these marker genes
specific to uterine leiomyomas, we established a hierarchical clustering system
based on the DNA methylation level of the marker genes, which could completely
differentiate between uterine leiomyomas and normal myometrium. Furthermore, our
hierarchical clustering system completely discriminated uterine cancers and
differentiated between uterine leiomyosarcomas and leiomyomas with more than 70%
accuracy. In conclusion, this study identified DNA methylation-based marker genes
specific to uterine leiomyomas, and our hierarchical clustering system using
these marker genes was useful for differential diagnosis of uterine leiomyomas
and leiomyosarcomas.
PMID- 27498621
TI - XIAP inhibits mature Smac-induced apoptosis by degrading it through
ubiquitination in NSCLC.
AB - X-linked inhibitor of apoptosis protein (XIAP) and second mitochondrial-derived
activator of caspase (Smac) are two important prognostic biomarkers for cancer.
They are negatively correlated in many types of cancer. However, their
relationship is still unknown in lung cancer. In the present study, we found that
there was a negative correlation between Smac and XIAP at the level of protein
but not mRNA in NSCLC patients. However, XIAP overexpression had no effect on
degrading endogenous Smac in lung cancer cell lines. Therefore, we constructed
plasmids with full length of Smac (fSmac) and mature Smac (mSmac) which located
in cytoplasm instead of original mitochondrial location, and was confirmed by
immunofluorescence. Subsequently, we found that mSmac rather than fSmac was
degraded by XIAP and inhibited cell viability. CHX chase assay and ubiquitin
assay were performed to illustrate XIAP degraded mSmac through ubiquitin pathway.
Overexpression of XIAP partially reverted apoptotic induction and cell viability
inhibition by mSmac, which was due to inhibiting caspase-3 activation. In nude
mouse xenograft experiments, mSmac inhibited Ki-67 expression and slowed down
lung cancer growth, while XIAP partially reversed the effect of mSmac by
degrading it. In conclusion, XIAP inhibits mature Smac-induced apoptosis by
degrading it through ubiquitination in NSCLC.
PMID- 27498623
TI - Direct Evidence of Solution-Mediated Superoxide Transport and Organic Radical
Formation in Sodium-Oxygen Batteries.
AB - Advanced large-scale electrochemical energy storage requires cost-effective
battery systems with high energy densities. Aprotic sodium-oxygen (Na-O2)
batteries offer advantages, being comprised of low-cost elements and possessing
much lower charge overpotential and higher reversibility compared to their
lithium-oxygen battery cousins. Although such differences have been explained by
solution-mediated superoxide transport, the underlying nature of this mechanism
is not fully understood. Water has been suggested to solubilize superoxide via
formation of hydroperoxyl (HO2), but direct evidence of these HO2 radical species
in cells has proven elusive. Here, we use ESR spectroscopy at 210 K to identify
and quantify soluble HO2 radicals in the electrolyte-cold-trapped in situ to
prolong their lifetime-in a Na-O2 cell. These investigations are coupled to
parallel SEM studies that image crystalline sodium superoxide (NaO2) on the
carbon cathode. The superoxide radicals were spin-trapped via reaction with 5,5
dimethyl-pyrroline N-oxide at different electrochemical stages, allowing
monitoring of their production and consumption during cycling. Our results
conclusively demonstrate that transport of superoxide from cathode to electrolyte
leads to the nucleation and growth of NaO2, which follows classical mechanisms
based on the variation of superoxide content in the electrolyte and its
correlation with the crystallization of cubic NaO2. The changes in superoxide
content upon charge show that charge proceeds through the reverse solution
process. Furthermore, we identify the carbon-centered/oxygen-centered alkyl
radicals arising from attack of these solubilized HO2 species on the diglyme
solvent. This is the first direct evidence of such species, which are likely
responsible for electrolyte degradation.
PMID- 27498622
TI - Protection associated with a TB vaccine is linked to increased frequency of Ag85A
specific CD4(+) T cells but no increase in avidity for Ag85A.
AB - There is a need to improve the efficacy of Bacille Calmette-Guerin (BCG)
vaccination against tuberculosis in humans and cattle. Previously, we found
boosting BCG-primed cows with recombinant human type 5 adenovirus expressing
antigen 85A (Ad5-85A) increased protection against Mycobacterium bovis infection
compared to BCG vaccination alone. The aim of this study was to decipher aspects
of the immune response associated with this enhanced protection. We compared BCG
primed Ad5-85A-boosted cattle with BCG-vaccinated cattle. Polyclonal CD4(+) T
cell libraries were generated from pre-boost and post-boost peripheral blood
mononuclear cells - using a method adapted from Geiger et al. (2009) - and
screened for antigen 85A (Ag85A) specificity. Ag85A-specific CD4(+) T cell lines
were analysed for their avidity for Ag85A and their Ag85A epitope specificity was
defined. Boosting BCG with Ad5-85A increased the frequencies of post-boost Ag85A
specific CD4(+) T cells which correlated with protection (reduced pathology).
Boosting Ag85A-specific CD4(+) T cell responses did not increase their avidity.
The epitope specificity was variable between animals and we found no clear
evidence for a post-boost epitope spreading. In conclusion, the protection
associated with boosting BCG with Ad5-85A is linked with increased frequencies of
Ag85A-specific CD4(+) T cells without increasing avidity or widening of the Ag85A
specific CD4(+) T cell repertoire.
PMID- 27498624
TI - Reaching across the shores to strengthen primary care.
PMID- 27498625
TI - Real and illusory issues in the illusion debate (Why two things are sometimes
better than one): Commentary on Kopiske et al. (2016).
PMID- 27498627
TI - RUNX3 plays an important role in As2O3-induced apoptosis and allows cells to
overcome MSC-mediated drug resistance.
AB - The interaction between bone marrow stromal cells and leukemia cells is critical
for the persistence and progression of leukemia, and this interaction may account
for residual disease. However, the link between leukemia cells and their
environment is still poorly understood. In our study, runt-related transcription
factor 3 (RUNX3) was identified as a novel target gene affected by As2O3 and
involved in mesenchymal stem cell (MSC)-mediated protection of leukemia cells
from As2O3-induced apoptosis. We observed induction of RUNX3 expression and the
translocation of RUNX3 into the nucleus after As2O3 treatment in leukemia cells.
In K562 chronic myeloid leukemia cells, downregulation of endogenous RUNX3
compromised As2O3-induced growth inhibition, cell cycle arrest, and apoptosis. In
the presence of MSC, As2O3-induced expression of RUNX3 was reduced significantly
and this reduction was modulated by CXCL12/CXCR4 signaling. Furthermore,
overexpression of RUNX3 restored, at least in part, the sensitivity of leukemic
cells to As2O3. We conclude that RUNX3 plays an important role in As2O3-induced
cellular responses and allows cells to overcome MSC-mediated drug resistance.
Therefore, RUNX3 is a promising target for therapeutic approaches to overcome MSC
mediated drug resistance.
PMID- 27498628
TI - Diaza [1,4] Wittig-type rearrangement of N-allylic-N-Boc-hydrazines into gamma
amino-N-Boc-enamines.
AB - Diaza [1,4] Wittig-type rearrangement of N-allylic-N-Boc-hydrazines into gamma
amino-N-Boc-enamines was demonstrated. The scope and limitation, experimental
mechanistic studies, and a proposed reaction mechanism were also described.
PMID- 27498626
TI - Should urinary iodine concentrations of school-aged children continue to be used
as proxy for different populations? Analysis of data from Chinese national
surveys.
AB - I deficiency is a worldwide public health problem. Median urinary I concentration
in school-aged children has been used globally as a proxy for all populations.
This study aims to determine whether median urinary I concentration of school
aged children is an appropriate indicator of I nutritional status in different
adult populations. This is a secondary data analysis of two national I Deficiency
Disorder surveys (2011, 2014) and two regional surveys (in coastal areas, 2009,
and in high-risk areas, 2009-2014). Population groups included in these surveys
were school-aged children (8-10 years), pregnant women, lactating women, women of
childbearing age and adults (men and women, 18-45 years). All participants were
self-reported healthy without history of thyroid diseases or were not using
thyroid medicines. The median urinary I concentration of school-aged children was
matched with that of the other population at the county level. The matched
populations had similar iodised salt supply, food and water I, food composition
and I content in salt. Weak or moderate correlation of median urinary I
concentrations was observed between school-aged children and pregnant women and
between children and lactating women. However, the agreement was stronger between
children and women of childbearing age and between children and adult men and
women. The results could be affected by cut-off values, data aggregation level
and sample size. Using median urinary I concentration of school-aged children
tends to overestimate that of pregnant women and lactating women. Median urinary
I concentration of school-aged children can be used for assessing I nutrition in
the adult population.
PMID- 27498629
TI - Tuberculosis in newly arrived asylum seekers: A prospective 12 month surveillance
study at Friedland, Germany.
AB - PURPOSE: In the European Union tuberculosis prevalence-rates are among the lowest
in the world. The prevalence of active tuberculosis in migrant populations has to
be analyzed to get valid data on the risk of tuberculosis and for the decision of
screening activities. METHODS: Therefore, we prospectively quantified the risk of
active tuberculosis among asylum seekers at time of arrival. Investigation was
performed as regular part of the admission screenings for people arriving at
Friedland, Germany, a primary major receiving center during one year. RESULTS: In
11.773 newly arrived asylum seekers 16 X-ray investigations gave the suspicion of
active tuberculosis, thereof 11 cases could be verified by culture, thereof 9
cases were classified as microscopically positive. These data translate into
rates of 136 per 100.000 suspected cases, 93 per 100.000 verified cases, and
finally 76 per 100.000 infectious cases, respectively. Prevalence was higher in
asylum seekers coming from Eritrea and Russia compared to the main origins of
current migration Syria, Afghanistan, Iraq, Iran, and Lebanon. One case of MDR
tuberculosis could be detected in a migrant from Russia. CONCLUSIONS: Prevalence
rates of tuberculosis in newly arrived asylum seekers are higher than in native
European populations. Rates seem to reflect the prevalence in the home countries.
X-ray investigation during first examination may help identifying people needing
further tests for detecting infectious tuberculosis and therefore may prevent
transmission. However due to the low prevalence rates screening procedures have
to be reviewed.
PMID- 27498630
TI - Post-industrial river water quality-Fit for bathing again?
AB - For the Ruhr River, bathing has been prohibited for decades. However, along with
significant improvements of the hygienic water quality, there is an increasing
demand of using the river for recreational purposes, in particular for bathing.
In the "Safe Ruhr" interdisciplinary research project, demands, options and
chances for lifting the bathing ban for the Ruhr River were investigated. As
being the prominent reason for persisting recreational restrictions,
microbiological water quality was in the focus of interest. Not only the faecal
indicator organisms (FIOs) as required by the European Bathing Water Directive
were considered, but also pathogens such as Salmonella, Pseudomonas aeruginosa,
Legionella pneumophila, Campylobacter, Leptospira, enteroviruses and protozoan
parasites. In this introductory paper, we firstly relate current recreational
desires to historical experiences of river bathing. After recapitulating relevant
microbial river contamination sources (predominantly sewage treatment plants,
combined sewer overflows, and surface runoffs), we review existing knowledge
about the relationships of FIOs and pathogens in rivers designated for
recreational purposes, and then trace the evolution, rationale and validity of
recreational freshwater quality criteria which are, despite obvious
uncertainties, mostly relying on the FIO paradigm. In particular, the
representativeness of FIOs is critically discussed. The working programme of Safe
Ruhr, aiming at initiating and facilitating a process towards legalisation of
Ruhr River bathing, is outlined. Sources of contamination can be technically
handled which leaves the actual measures to political decisions. As
contaminations are transient, only occasionally exceeding legal limits, a
flexible bathing site management, warning bathers of non-safe situations, may
amend technical interventions and offer innovative solutions. As a result, a
situation-adapted system for lifting of the bathing ban for Ruhr River appears
realistic.
PMID- 27498631
TI - The role of carbohydrate component of recombinant alpha7 nicotinic acetylcholine
receptor extracellular domain in its immunogenicity and functional effects of
resulting antibodies.
AB - Nicotinic acetylcholine receptors of alpha7 subtype (alpha7 nAChRs) attenuate the
inflammatory cytokines production by macrophages and are involved in pathogenesis
of Alzheimer disease by directly influencing the processing of amyloid-beta
(Abeta) precursor protein in the brain. Previously we found that regular
injections of bacterial lipopolysaccharide (LPS) decreased the level of alpha7
nAChRs and stimulated accumulation of Abeta peptide (1-42) in the brain of mice
resulting in memory impairment. Similar effects were observed in mice immunized
with recombinant extracellular domain (1-208) of alpha7 nAChR subunit. However,
the mechanism of inflammation-like effect of alpha7-specific antibodies remained
unclear. The aim of the present study was to reveal the impact of carbohydrate
component of recombinant alpha7(1-208) produced in yeast in the functional effect
of resulting antibodies. For this purpose, C57Bl/6 mice were immunized with
either initial alpha7(1-208) or with that pre-treated with endoglycosidase.
Control groups of mice obtained injections of either LPS or complete Freund's
adjuvant. Mice were tested for memory performance, their blood sera were examined
for the presence and fine specificity of alpha7(1-208)-specific antibodies and
the brain preparations were studied for the levels of alpha7 nAChR, Abeta(1-42)
and interleukin-6. It was found that the original alpha7(1-208) was more
immunogenic than the deglycosylated one, and their epitopes were recognized with
different efficiency. In contrast to LPS and original alpha7(1-208),
deglycosylated alpha7(1-208) did not stimulate interleukin-6 elevation in the
brain, i.e. had no pro-inflammatory effect. Nevertheless, immunizations with
either the original or deglycosylated alpha7(1-208) resulted in similar decrease
of alpha7 nAChRs, accumulation of Abeta(1-42) in the brain and significant
episodic memory decline, comparable to those exerted by LPS injections. We
conclude that the decrease of alpha7 nAChR density, caused by alpha7(1-208)
specific antibody, is critical for Abeta(1-42) accumulation and episodic memory
impairment, while pro-inflammatory capacity of alpha7(1-208)-specific antibody
plays a secondary role for the development of Alzheimer-like symptoms.
PMID- 27498632
TI - The Role of Molecular Dynamics Potential of Mean Force Calculations in the
Investigation of Enzyme Catalysis.
AB - The potential of mean force simulations, widely applied in Monte Carlo or
molecular dynamics simulations, are useful tools to examine the free energy
variation as a function of one or more specific reaction coordinate(s) for a
given system. Implementation of the potential of mean force in the simulations of
biological processes, such as enzyme catalysis, can help overcome the
difficulties of sampling specific regions on the energy landscape and provide
useful insights to understand the catalytic mechanism. The potential of mean
force simulations usually require many, possibly parallelizable, short
simulations instead of a few extremely long simulations and, therefore, are
fairly manageable for most research facilities. In this chapter, we provide
detailed protocols for applying the potential of mean force simulations to
investigate enzymatic mechanisms for several different enzyme systems.
PMID- 27498633
TI - Empirical Force Fields for Mechanistic Studies of Chemical Reactions in Proteins.
AB - Following chemical reactions in atomistic detail is one of the most challenging
aspects of current computational approaches to chemistry. In this chapter the
application of adiabatic reactive MD (ARMD) and its multistate version (MS-ARMD)
are discussed. Both methods allow to study bond-breaking and bond-forming
processes in chemical and biological processes. Particular emphasis is put on
practical aspects for applying the methods to investigate the dynamics of
chemical reactions. The chapter closes with an outlook of possible
generalizations of the methods discussed.
PMID- 27498634
TI - Generalized Ensemble Sampling of Enzyme Reaction Free Energy Pathways.
AB - Free energy path sampling plays an essential role in computational understanding
of chemical reactions, particularly those occurring in enzymatic environments.
Among a variety of molecular dynamics simulation approaches, the generalized
ensemble sampling strategy is uniquely attractive for the fact that it not only
can enhance the sampling of rare chemical events but also can naturally ensure
consistent exploration of environmental degrees of freedom. In this review, we
plan to provide a tutorial-like tour on an emerging topic: generalized ensemble
sampling of enzyme reaction free energy path. The discussion is largely focused
on our own studies, particularly ones based on the metadynamics free energy
sampling method and the on-the-path random walk path sampling method. We hope
that this minipresentation will provide interested practitioners some meaningful
guidance for future algorithm formulation and application study.
PMID- 27498635
TI - Methods for Efficiently and Accurately Computing Quantum Mechanical Free Energies
for Enzyme Catalysis.
AB - Enzyme activity is inherently linked to free energies of transition states,
ligand binding, protonation/deprotonation, etc.; these free energies, and thus
enzyme function, can be affected by residue mutations, allosterically induced
conformational changes, and much more. Therefore, being able to predict free
energies associated with enzymatic processes is critical to understanding and
predicting their function. Free energy simulation (FES) has historically been a
computational challenge as it requires both the accurate description of inter-
and intramolecular interactions and adequate sampling of all relevant
conformational degrees of freedom. The hybrid quantum mechanical molecular
mechanical (QM/MM) framework is the current tool of choice when accurate
computations of macromolecular systems are essential. Unfortunately, robust and
efficient approaches that employ the high levels of computational theory needed
to accurately describe many reactive processes (ie, ab initio, DFT), while also
including explicit solvation effects and accounting for extensive conformational
sampling are essentially nonexistent. In this chapter, we will give a brief
overview of two recently developed methods that mitigate several major challenges
associated with QM/MM FES: the QM non-Boltzmann Bennett's acceptance ratio method
and the QM nonequilibrium work method. We will also describe usage of these
methods to calculate free energies associated with (1) relative properties and
(2) along reaction paths, using simple test cases with relevance to enzymes
examples.
PMID- 27498636
TI - Born-Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of Enzyme
Reactions.
AB - There are two key requirements for reliably simulating enzyme reactions: one is a
reasonably accurate potential energy surface to describe the bond
forming/breaking process as well as to adequately model the heterogeneous enzyme
environment; the other is to perform extensive sampling since an enzyme system
consists of at least thousands of atoms and its energy landscape is very complex.
One attractive approach to meet both daunting tasks is Born-Oppenheimer ab initio
QM/MM molecular dynamics (aiQM/MM-MD) simulation with umbrella sampling. In this
chapter, we describe our recently developed pseudobond Q-Chem-Amber interface,
which employs a combined electrostatic-mechanical embedding scheme with periodic
boundary condition and the particle mesh Ewald method for long-range
electrostatics interactions. In our implementation, Q-Chem and the sander module
of Amber are combined at the source code level without using system calls, and
all necessary data communications between QM and MM calculations are achieved via
computer memory. We demonstrate the applicability of this pseudobond Q-Chem-Amber
interface by presenting two examples, one reaction in aqueous solution and one
enzyme reaction. Finally, we describe our established aiQM/MM-MD enzyme
simulation protocol, which has been successfully applied to study more than a
dozen enzymes.
PMID- 27498637
TI - QM/MM Calculations on Proteins.
AB - In this chapter, I discuss combined quantum mechanics (QM) and molecular
mechanics (MM; QM/MM) calculations for proteins. In QM/MM, a small but
interesting part of the protein is treated by accurate QM methods, whereas the
remainder is treated by faster MM methods. The prime problems with QM/MM
calculations are bonds between the QM and MM systems, the selection of the QM
system, and the local-minima problem. The two first problems can be solved by the
big-QM approach, including in the QM calculation all groups within 4.5-6A of the
active site and all buried charges in the protein. The third problem can be
solved by calculating free energies. It is important to study QM/MM energy
components to ensure that the results are stable and reliable. They can also be
used to understand the reaction and the effect of the surroundings, eg, by
dividing the catalytic effect into bonded, van der Waals, electrostatic, and
geometric components and to deduce which parts of the protein contribute most to
the catalysis. It should be ensured that the QM calculations are reliable and
converged by extending the basis set to quadruple-zeta quality, including a
proper treatment of dispersion, as well as years experience and method
development calculations with both pure and hybrid density functional theory
methods. If the latter give differing results, calibration with high-level QM
methods is needed. Reactions that change the net charge should be avoided. QM/MM
calculations can be combined with experimental methods.
PMID- 27498638
TI - Enzymatic Cleavage of Glycosidic Bonds: Strategies on How to Set Up and Control a
QM/MM Metadynamics Simulation.
AB - Carbohydrates play crucial roles in many biological processes, from cell-cell
adhesion to chemical signaling. Their complexity and diversity, related to
alpha/beta anomeric configuration, ring substituents, and conformational
variations, require a diverse set of enzymes for their processing. Among them,
glycoside hydrolases (GHs) are responsible for the hydrolysis of one of the
strongest bonds in nature: the glycosidic bond. These highly specialized
biological catalysts select particular conformations their carbohydrate
substrates to enhance catalysis. The evolution of this conformation during the
reaction of glycosidic bond cleavage, known as the conformational catalytic
itinerary, is of fundamental interest in glycobiology, with impact on inhibitor
and drug design. Here we review some of the aspects and the main strategies one
needs to take into account when simulating a reaction in a GH enzyme using QM/MM
metadynamics. Several specific aspects are highlighted, from the importance of
the distortion of the substrate at the Michaelis complex to the variable control
during the metadynamics simulation or the analysis of the reaction mechanism and
conformational itinerary. The increasing speed of computer power and
methodological advances have added a vital tool to the study of GH mechanisms, as
shown here and recent reviews. It is hoped that this chapter will serve as a
first guide for those attempting to perform a metadynamics simulation of these
relevant and fascinating enzymes.
PMID- 27498639
TI - Toward Determining ATPase Mechanism in ABC Transporters: Development of the
Reaction Path-Force Matching QM/MM Method.
AB - Adenosine triphosphate (ATP)-binding cassette (ABC) transporters are ubiquitous
ATP-dependent membrane proteins involved in translocations of a wide variety of
substrates across cellular membranes. To understand the chemomechanical coupling
mechanism as well as functional asymmetry in these systems, a quantitative
description of how ABC transporters hydrolyze ATP is needed. Complementary to
experimental approaches, computer simulations based on combined quantum
mechanical and molecular mechanical (QM/MM) potentials have provided new insights
into the catalytic mechanism in ABC transporters. Quantitatively reliable
determination of the free energy requirement for enzymatic ATP hydrolysis,
however, requires substantial statistical sampling on QM/MM potential. A case
study shows that brute force sampling of ab initio QM/MM (AI/MM) potential energy
surfaces is computationally impractical for enzyme simulations of ABC
transporters. On the other hand, existing semiempirical QM/MM (SE/MM) methods,
although affordable for free energy sampling, are unreliable for studying ATP
hydrolysis. To close this gap, a multiscale QM/MM approach named reaction path
force matching (RP-FM) has been developed. In RP-FM, specific reaction parameters
for a selected SE method are optimized against AI reference data along reaction
paths by employing the force matching technique. The feasibility of the method is
demonstrated for a proton transfer reaction in the gas phase and in solution. The
RP-FM method may offer a general tool for simulating complex enzyme systems such
as ABC transporters.
PMID- 27498641
TI - Practical Aspects of Multiscale Classical and Quantum Simulations of Enzyme
Reactions.
AB - This chapter aims to present some basic multiscale approaches available for
enzyme simulations, and to point out practical details and pitfalls that are not
often discussed in the literature, but can greatly influence the outcome of any
in silico enzyme study. We cover principle methodological steps of multiscale
studies of general enzyme reactions. This includes choice of starting structures,
boundary conditions, potential energy surfaces, reaction coordinates, simulation
methods, as well as the choice of method for the treatment of nuclear quantum
effects. Together, these and additional steps are crucial for the success of
enzyme-modeling projects and should be considered prior to embarking on
multiscale modeling.
PMID- 27498640
TI - QM/MM Analysis of Transition States and Transition State Analogues in
Metalloenzymes.
AB - Enzymology is approaching an era where many problems can benefit from
computational studies. While ample challenges remain in quantitatively predicting
behavior for many enzyme systems, the insights that often come from computations
are an important asset for the enzymology community. Here we provide a primer for
enzymologists on the types of calculations that are most useful for mechanistic
problems in enzymology. In particular, we emphasize the integration of models
that range from small active-site motifs to fully solvated enzyme systems for
cross-validation and dissection of specific contributions from the enzyme
environment. We then use a case study of the enzyme alkaline phosphatase to
illustrate specific application of the methods. The case study involves
examination of the binding modes of putative transition state analogues
(tungstate and vanadate) to the enzyme. The computations predict covalent binding
of these ions to the enzymatic nucleophile and that they adopt the trigonal
bipyramidal geometry of the expected transition state. By comparing these
structures with transition states found through free energy simulations, we
assess the degree to which the transition state analogues mimic the true
transition states. Technical issues worth treating with care as well as several
remaining challenges to quantitative analysis of metalloenzymes are also
highlighted during the discussion.
PMID- 27498643
TI - Use of QM/DMD as a Multiscale Approach to Modeling Metalloenzymes.
AB - Enzymes are complex biomolecules capable of performing unique catalysis under
physiological conditions at neutral temperature and pH. However, the architecture
of enzymatic catalysis is often a combination of the quantum influence of the
immediate active site, as well as the electrostatic and configurational
influences of amino acids surrounding the active site. As a result of this
cooperation between baseline chemical reactivity and electrostatic assistance, it
has become important to model enzymes using multiscale methods that take
advantage of treating the active site with quantum mechanical methods, while
approximately treating the surrounding protein using cheaper, classically driven
force-field molecular mechanics methods. Here we describe the use of a multiscale
engine which utilizes a combination of density functional theory with discrete
molecular dynamics (dubbed QM/DMD) to aid in the characterization of
metalloenzymes.
PMID- 27498642
TI - Examinations of the Chemical Step in Enzyme Catalysis.
AB - Advances in computational and experimental methods in enzymology have aided
comprehension of enzyme-catalyzed chemical reactions. The main difficulty in
comparing computational findings to rate measurements is that the first examines
a single energy barrier, while the second frequently reflects a combination of
many microscopic barriers. We present here intrinsic kinetic isotope effects and
their temperature dependence as a useful experimental probe of a single chemical
step in a complex kinetic cascade. Computational predictions are tested by this
method for two model enzymes: dihydrofolate reductase and thymidylate synthase.
The description highlights the significance of collaboration between
experimentalists and theoreticians to develop a better understanding of enzyme
catalyzed chemical conversions.
PMID- 27498644
TI - Adaptive Partitioning QM/MM Dynamics Simulations for Substrate Uptake, Product
Release, and Solvent Exchange.
AB - Combined quantum mechanics/molecular mechanics (QM/MM) plays an important role in
multiscale simulations of biological systems including enzymes. The adaptive
partitioning (AP) schemes surpass the conventional QM/MM methods in that they
allow the on-the-fly, smooth exchange of particles between QM and MM subsystems
in molecular dynamics simulations, leading to a seamless and dynamic integration
of the QM and MM realms. Originally developed for simulating ion solvation in
bulk solutions, the AP schemes have recently been extended to the treatment of
proteins, fostering applications in the simulations of enzymes. The present
contribution provides a detailed account of the AP schemes. We delineate the
background of the algorithms and their parallel implementation, as well as offer
practical advice and examples for their applications in the simulations of
biological systems.
PMID- 27498646
TI - Simulating Nuclear and Electronic Quantum Effects in Enzymes.
AB - An accurate treatment of the structures and dynamics that lead to enhanced
chemical reactivity in enzymes requires explicit treatment of both electronic and
nuclear quantum effects. The former can be captured in ab initio molecular
dynamics (AIMD) simulations, while the latter can be included by performing ab
initio path integral molecular dynamics (AI-PIMD) simulations. Both AIMD and AI
PIMD simulations have traditionally been computationally prohibitive for large
enzymatic systems. Recent developments in streaming computer architectures and
new algorithms to accelerate path integral simulations now make these simulations
practical for biological systems, allowing elucidation of enzymatic reactions in
unprecedented detail. In this chapter, we summarize these recent developments and
discuss practical considerations for applying AIMD and AI-PIMD simulations to
enzymes.
PMID- 27498645
TI - Enzymatic Kinetic Isotope Effects from Path-Integral Free Energy Perturbation
Theory.
AB - Path-integral free energy perturbation (PI-FEP) theory is presented to directly
determine the ratio of quantum mechanical partition functions of different
isotopologs in a single simulation. Furthermore, a double averaging strategy is
used to carry out the practical simulation, separating the quantum mechanical
path integral exactly into two separate calculations, one corresponding to a
classical molecular dynamics simulation of the centroid coordinates, and another
involving free-particle path-integral sampling over the classical, centroid
positions. An integrated centroid path-integral free energy perturbation and
umbrella sampling (PI-FEP/UM, or simply, PI-FEP) method along with bisection
sampling was summarized, which provides an accurate and fast convergent method
for computing kinetic isotope effects for chemical reactions in solution and in
enzymes. The PI-FEP method is illustrated by a number of applications, to
highlight the computational precision and accuracy, the rule of geometrical mean
in kinetic isotope effects, enhanced nuclear quantum effects in enzyme catalysis,
and protein dynamics on temperature dependence of kinetic isotope effects.
PMID- 27498647
TI - Using Molecular Simulation to Study Biocatalysis in Ionic Liquids.
AB - The practice of computational biocatalysis in ionic liquids (ILs) is still in its
infancy, and thus best simulation practices are still developing. Herein, we
examine the computational and experimental literature to date featuring systems
of enzymes in aqueous and neat ILs. The many different approaches taken to
parameterize ILs and set up simulations of enzymes in ILs are discussed, and
common analysis techniques are reviewed. We also shed light on potential
drawbacks and limitations to simulating enzymes in ILs, which include a lack of
experimental data with which to validate computational models and inadequate
sampling arising from the slow dynamics of many ILs that can lead to inaccurate
descriptions of transport and equilibrium thermodynamic properties. A small case
study illustrates the effects of scaling IL partial charges, which is a common
practice in the field, on the conformational transitions of alanine dipeptide.
The degree of charge scaling has a significant effect on the transition times
between states of the biomolecule and highlights the importance of carefully
setting up systems of enzymes in ILs. Finally, we discuss means to overcome these
challenges and briefly consider possible new directions for the field.
PMID- 27498649
TI - Preface.
PMID- 27498650
TI - A novel methodology for assessing the environmental sustainability of ionic
liquids used for CO2 capture.
AB - Ionic liquids (ILs) have been proposed as suitable sorbents for CO2 capture
because of their high CO2 absorption capacity, thermal stability, negligible
vapour pressure and physico-chemical tunability. However, the environmental
implications of ILs are currently largely unknown because of a lack of data. The
issue is further complicated by their complex chemical structures and numerous
precursors for which environmental data are scarce or non-existent. In an attempt
to address this issue, this paper presents a new methodology for estimating life
cycle environmental impacts of novel ILs, with the aim of aiding synthesis and
selection of more sustainable CO2 sorbents. The methodology consists of four main
steps: (1) selection of an appropriate IL and synthesis route; (2) construction
of a life cycle tree; (3) life cycle assessment; and (4) recommendations for
improvements. The application of the methodology is illustrated using
trihexyltetradecylphosphonium 1,2,4-triazolide ([P66614][124Triz]), a promising
IL for CO2 capture currently under development. Following the above steps, the
paper demonstrates how the data obtained from laboratory synthesis of the IL can
be scaled up to industrial production to estimate life cycle impacts and identify
environmental hotspots. In this particular case, the main hotspots are the
precursors used in the synthesis of the IL. Comparison of impacts with
monoethanolamine (MEA), currently the most widely-used CO2 sorbent, suggests that
[P66614][124Triz] has much higher impacts than MEA, including global warming
potential. However, human toxicity potential is significantly higher for MEA.
Therefore, the proposed methodology can be used to optimise the design of ILs and
to guide selection of more sustainable CO2 sorbents. Although the focus is on
ILs, the methodology is generic and can be applied to other chemicals under
development.
PMID- 27498651
TI - A multi-centred open trial of ?Dr Michaels(r)? (also branded as Soratinex(r))
topical product family in psoriasis.
AB - Psoriasis is a chronic, recurring skin disease affecting 2-4% of the population.
Genetic predisposition and precipitating factors play a role in its etiology. The
disease can occur in any age or gender group. The most frequently affected areas
of the body include scalp, extensor surfaces of the extremities, skin folds and
nails. While a number of therapies exist for the treatment of psoriasis with a
total resolution of the skin, achieving remission in a high percentage of
sufferers, a treatment that results in the maintenance of remission and is free
of side effects is still a desirable goal. The aim of the study was to
investigate the efficacy and tolerability of Dr Michaels(r) (Soratinex(r))
topical product family in psoriasis, in terms of decreasing parakeratosis,
inflammation, infiltration and involved area. Seven-hundred-and-twenty-two
subjects, mean age 42.3 years (range: 18-68 years) with mild to moderately severe
psoriasis, with no other current anti-psoriatic therapy, consisting of 382 males
and 340 females, above 18 years of age were included and the observations were
subjected to statistical analysis. Triphasic application of Dr Michaels(r)
(Soratinex(r)) products was employed for 8 weeks, using Cleansing Gel, Scalp and
Body Ointment and Skin Conditioner. The treatment proved to be ineffective for 22
patients (3.1%) out of 722. 84 patients (11.6%) had moderate improvement with 26
50% of cleared skin lesions; 102 patients (14.1%) had good improvement with 51
75% of cleared skin lesions; 484 patients (67.0%) experienced outstanding
improvement with 76-100% of the cleared skin lesions, with 52% of them achieving
total resolution. Twelve patients worsened and discontinued treatment; 18
patients discontinued because of non-compliance; 33 patients developed
folliculitis as a side effect. Based on the results of this study, the Dr
Michaels(r) (Soratinex(r)) product family can be successfully applied in mild to
moderately severe psoriasis when considering the exclusion criteria.
PMID- 27498652
TI - A European prospective, randomized placebo-controlled doubleblind Study on the
efficacy and safety of Dr Michaels(r) (also branded as Soratinex(r)) product
family for stable chronic plaque psoriasis.
AB - Psoriasis is a chronic, inflammatory, recurrent, genetically determined
dermatitis that affects the skin and joints. Many patients affected by this
condition seek alternatives and complementary treatment options such as herbal
medicines. In order to establish the safety of these products, trials, according
to medical standards should be performed to provide the highest quality of data.
The aim of this study was to assess the efficacy and safety of an Australian
series of herbal skincare products [Dr. Michaels(r) (Soratinex(r)) skin-care
products for psoriasis] for the management of stable chronic plaque psoriasis. We
studied 142 patients (68 females and 74 males) with mild to moderate, stable,
chronic plaque psoriasis and they were randomly assigned to either verum or
control group. Exclusion criteria were: severe psoriasis, arthropathic psoriasis,
intertriginous psoriasis, palmoplantar psoriasis, use of any antipsoriatic
treatment and any medication which could influence or interfere with the course
of the disease. Both groups consisted of a cleansing gel, an ointment and an oil
blend (skin conditioner), packed in neutral bottles, used twice daily for all
lesions except the scalp, for 8 weeks. As control products, we used compositions
of well-known neutral ointments and medicinal bathing oil. Assessment, using the
Psoriasis Activity Severity Index (PASI) scores, was done before treatment and
after 2, 4, 6 and 8 weeks. Patient improvement was determined by the percentage
reduction of the PASI scores. Statistical analysis was carried out using the Mann
Whitney-U Test with SPSS for Windows. Our investigation demonstrates that
complementary methods can play a role in dermatologic therapy as long as they
undergo standardised clinical trials and fulfil the basic requirements such as
product safety and quality assurance. This study shows that Dr Michaels
(Soratinex(r)) herbal skin-care products improve mild to moderate stable chronic
plaque psoriasis significantly.
PMID- 27498648
TI - The MOD-QM/MM Method: Applications to Studies of Photosystem II and DNA G
Quadruplexes.
AB - Quantum mechanics/molecular mechanics (QM/MM) hybrid methods are currently the
most powerful computational tools for studies of structure/function relations and
catalytic sites embedded in macrobiomolecules (eg, proteins and nucleic acids).
QM/MM methodologies are highly efficient since they implement quantum chemistry
methods for modeling only the portion of the system involving bond
breaking/forming processes (QM layer), as influenced by the surrounding molecular
environment described in terms of molecular mechanics force fields (MM layer).
Some of the limitations of QM/MM methods when polarization effects are not
explicitly considered include the approximate treatment of electrostatic
interactions between QM and MM layers. Here, we review recent advances in the
development of computational protocols that allow for rigorous modeling of
electrostatic interactions in biomacromolecules and structural refinement, beyond
the common limitations of QM/MM hybrid methods. We focus on photosystem II (PSII)
with emphasis on the description of the oxygen-evolving complex (OEC) and its
high-resolution extended X-ray absorption fine structure spectra (EXAFS) in
conjunction with Monte Carlo structural refinement. Furthermore, we review QM/MM
structural refinement studies of DNA G4 quadruplexes with embedded monovalent
cations and direct comparisons to NMR data.
PMID- 27498653
TI - A clinical examination of the efficacy of preparation of Dr Michaels(r) (also
branded as Soratinex(r)) products in the treatment of psoriasis.
AB - Psoriasis is a chronic inflammatory disease with negative impacts both physically
and psychologically. It is a common disorder affecting 2-3% of the total world
population, in some cases causing changes to the nail and joints as well as skin
lesions. The cutaneous manifestations of psoriasis can vary in morphology and
severity and therapy should be tailored accordingly. The aim of the study was to
investigate the efficacy of Dr Michaels(r) (Soratinex(r)) product line in the
treatment of psoriatic patients with different age and disease severity. A total
number of 270 patients with verified psoriasis, aged 9-60 years old participated
in the studies, including 128 children: 23 girls and 105 boys, (all of them
selected from the Department of Dermato-allergology of the Russian Pediatric
Hospital Clinic, Moscow, and of the 4th Department of Dermatology of the 52nd
Moscow City Hospital Clinic). The patients were separated into 3 groups according
to the severity of the disease (based on the PASI-index). All the patients have
been treated with Dr Michaels(r) (Soratinex(r)) products twice daily, as three
different forms were available for application: a cleansing gel, an ointment and
a conditioner. The severity of the disease and the efficacy of the treatment have
been defined with the evaluation of the PASI index of each patient. The obtained
results were recorded in a graphic form showing the changes of the PASI-index on
days 3, 7, 14, and 21 counted from the start of the trial. Clinical remission was
achieved in 147 patients, a significant improvement in 73, partial improvement in
32, while no effect was seen in 12 patients and deterioration in 6. This open
trial demonstrated the clinical efficacy of topical application of Dr Michaels(r)
(Soratinex(r)) preparation. We observed clinical remissions of psoriasis in
adults and in children.
PMID- 27498654
TI - Nail psoriasis in an adult successfully treated with a series of herbal skin care
products family ? a case report.
AB - Psoriasis is a common chronic inflammatory dermatosis that causes significant
distress and morbidity. Approximately 50% of patients with cutaneous psoriasis
and 90% of patients with psoriatic arthritis demonstrate nail involvement of
their psoriasis. Left untreated, nail psoriasis may progress to debilitating nail
disease that leads to not only impairment of function but also on quality of
life. We report the case of a 50-year-old male patient with recalcitrant nail
dystrophies on the fingers since the age of 40, who responded successfully to Dr.
Michaels(r) product family. The patient had a 35-year history of plaque psoriasis
localised on the scalp, ears, groin, limbs, and trunk and with psoriatic
arthritis. The nail symptoms consisted of onycholysis, onychomycosis,
leukonychia, transverse grooves, nail plate crumbling and paronychia of the
periungal skin. This case represents the efficacy and safety of the Dr.
Michaels(r) (Soratinex(r) and Nailinex(r)) product family with successful
resolution of nail dystrophies and surrounding paronychia with no reported
adverse events.
PMID- 27498655
TI - Clinical evaluation of the effectiveness of ?Dr Michaels(r)? (also branded as
Soratinex(r)) products in the topical treatment of patients with plaque
psoriasis.
AB - Psoriasis is generally considered as an autoimmune inflammatory cutaneous
systemic disease, with chronic course and high rate of recurrence, while its high
risk of comorbidities affect the patients? quality of life significantly. Despite
the good therapeutic response, most of the available options show tendency for
poor tolerance and high rate of occurrence of side effects. Therefore, the
interest of patients and doctors to investigate the possibility of treating
psoriasis with natural substances is not surprising. The aim of this study was to
investigate the efficacy and safety of the herbal skin-care product Dr
Michaels(r) (Soratinex(r)) for the management of chronic plaque psoriasis, within
a 6 to 8 week treatment course. Thirty patients of both sexes, aged between 24
and 70 years with mild to moderate psoriasis vulgaris were included in this
study. The products of Dr Michaels(r) (Soratinex(r)) were applied in sequence:
cleansing gel, ointment after 3-4 minutes and tonic care (for the fire-smeared
ointment) 2 times per day for restorative care and cleansing gel for psoriasis
within scalp 3 times a week. The study lasted six weeks. The severity and extent
of the lesions were evaluated by PASI score (Psoriasis Area and Severity Index).
Based on the obtained result, the products of ?Dr Michaels(r) (Soratinex(r))?
have proved to be effective in the treatment of mild and moderate psoriasis
vulgaris. In the study group, no improvement was observed in 10% of patients, a
slight improvement in 20%, good in 40% and very good in 16.6% of patients.
PMID- 27498656
TI - Successful treatment of a chronic eczema in a 48-year-old female with Dr
Michaels(r) (Eczitinex(r) and Itchinex(r)) product family. A case report.
AB - We report the case of a 48-year-old female with chronic atopic eczema who
responded successfully to Dr Michaels(r) (Eczitinex(r) and Itchinex(r)) product
family. The patient had a 41-year history of atopic eczema and presented with
erythematous, excoriated lesions with telangiectasia and scattered purpura
(bruising) covering 90% of her body surface area. The patient also regularly
suffered blepharitis with red, itchy, watery eyes. The patient was treated with
Dr Michaels(r) (Eczitinex(r) and Itchinex(r)) ointment and herbal supplements and
presented total resolution of the atopic eczema and underlying inflammation
within 6 weeks. This case also suggests that Dr Michaels(r) (Eczitinex(r) and
Itchinex(r)) product family is safe and effective, even in cortisone acquired
sensitive skin.
PMID- 27498657
TI - Dr Michaels(r) (Soratinex(r)) product for the topical treatment of psoriasis: a
Hungarian/Czech and Slovak study.
AB - Psoriasis is a chronic inflammatory T cell-mediated skin disease, affecting about
2% of Hungarian population. Genetic predisposition as well as environmental
triggering factors, and innate immune processes play a role in its etiology.
Treatment of psoriasis during the initial stages and first years of disease tend
to be conservative and frequently based on topical agents. The aim of this study
was to investigate and to describe the efficacy and safety of Dr Michaels(r)
(Soratinex(r)) skin-care products for the topical treatment of stable chronic
plaque psoriasis in a Hungarian population. Two-hundred-and-eight-six (120
female/166 male) patients, aged 10-80 years old (mean age 43 years) with mild to
moderate plaque psoriasis had participated in the study. The products, including
cleansing gel containing a coal tar solution, herbal oils and emulsifiers, were
used twice daily and in the same manner for all the skin lesions. The study
period was eight weeks. Assessment, using the Psoriasis Activity Severity Index
(PASI) scores and photographic analysis, was done 2 weeks before treatment, at
time 0, and after 2, 4, 6 and 8 weeks. Patient?s improvement was determined by
the percentage reduction of the PASI scores. Side effects and tolerability were
also evaluated. After 8 weeks treatment course, 46 patients had a moderate
improvement, with the regression of 25-50% of skin lesions; 77 patients showed a
good improvement, with the resolution of 51-75% of lesions. Another 115 patients
had an outstanding improvement, with the regression of 76-98.9% of lesions. Only
13 patients did not achieve an improvement of psoriasis. Fifteen patients
experienced folliculitis, which resolved after cessation of treatment. Seven
patients worsened and discontinued treatment. Thirteen patients dropped out
because of non-compliance. Our investigation demonstrates that Dr Michaels(r)
(Soratinex(r)) products, an Australian treatment, can be used successfully in the
treatment of stable chronic plaque psoriasis.
PMID- 27498658
TI - Successful treatment of mild to moderate acne vulgaris with Dr Michaels(r) (also
branded as Zitinex(r)) topical products family: a clinical trial.
AB - Acne vulgaris is an epidemic inflammatory skin disease of multi-factorial origin,
frequently seen in adolescents and often persisting or occurring through to
adulthood. Acne vulgaris is a nearly universal skin disease afflicting 79-95% of
the adolescent population in westernized societies and is a significant cause of
psychological morbidity in affected patients. Despite the various treatment
options available for acne, there is still a need for a safe and effective
option. The aim of the study was to investigate the efficacy and tolerability of
Dr Michaels(r) (Zitinex(r)) product family in the treatment of papulo-pustular
acne. 25 patients (17 female/8 male), aged 15-22, with a mild to moderate papulo
pustular acne, localized on the face and on the trunk, were included in this
study. None of the patients had used any other kind of treatment in the 3 months
prior to commencing this study. All of the patients were treated with Dr
Michaels(r) (Zitinex(r)) facial exfoliating cleanser, activator formula, a cream,
PSC 200 and PSC 900 oral supplements. Application time of Dr Michaels(r)
(Zitinex(r)) products was 12 weeks. The treatment was been evaluated clinically
at 0, 4, 8 and 12 weeks. All of the patients showed an improvement in all
parameters of their acne (comedones, papules, pustules, hyperpigmentation and
scars). The acne lesions and erythema had mostly resolved. The hyperpigmentation
and pitted scarring had significantly reduced also, with the skin appearing
smoother. The treatment was well tolerated and no side effects have been
described. Our study demonstrates that the Dr Michaels(r) (Zitinex(r)) facial
exfoliating cleanser, activator formula, cream and oral supplements PSC 200 and
PSC 900 are an effective therapeutic option for the treatment of moderately
severe acne vulgaris. Moreover, it highlights the safety profile of the Dr
Michaels(r) (Zitinex(r)) product family in a case of acne compared to traditional
first-line treatments.
PMID- 27498659
TI - Investigation of the efficacy and tolerability of Dr Michaels(r) (also branded as
Eczitinex(r) and Itchinex Eczitinex(r)) topical products in the treatment of
atopic dermatitis in children.
AB - Atopic eczema is a chronic relapsing inflammatory skin disorder, characterized
clinically by intensely pruritic eczematous skin lesions and a defective
epidermal barrier. It affects more than 15% of children and up to 10%of adults,
which makes the disease a social health problem still without a challenging
treatment. The aim of this study was to evaluate the efficacy and tolerability of
Dr Michaels(r) (Eczitinex(r)) topical product family in the treatment of atopic
dermatitis in children. We studied a group of 30 patients (17 female, 13 male),
aged 5 to 13 (mean age: 9), affected by atopic dermatitis since they were
newborn. All patients had been unsuccessfully treated with conventional anti
inflammatory therapies and ceased treatment 2 weeks before commencing research.
The patients were treated with Dr Michaels(r) (Eczitinex(r) and Itchinex(r))
product family including a moisturising bar, topical ointment and PSC 900 oral
herbal formulation. The treatment was evaluated clinically and photographically
at 0, 1, 2, 4, 6, 8, 10, 12, and 14 weeks. Twenty-eight patients showed a
significant improvement of cutaneous rashes and pruritus on the first week of
treatment, with a complete remission at 10-12 weeks. Only two patients, brother
and sister respectively, showed a slow response to treatment and reported an
increasing itching. Following 14 weeks of treatment with the Dr Michaels(r)
(Eczitinex(r) and Itchinex(r)) product family, patients demonstrated complete
resolution of their AD. All patients showed a marked improvement in their
condition within 3 days of treatment with most of the lesions and symptoms
totally resolved within 10 to 12 weeks of treatment with Dr Michaels(r)
(Eczitinex(r) and Itchinex(r)) family of products. This clinical report
highlights that the Dr Michaels(r) (Eczitinex(r) and Itchinex(r)) product family
is a safe and effective treatment option for AD.
PMID- 27498660
TI - Treatment of ichthyosis lamellaris using a series of herbal skin care products
family.
AB - Lamellar ichthyosis (LI) is a genetically heterogeneous group of disorders of
keratinization that are inherited in an autosomal recessive fashion, occurring in
approximately 1 in 300,000 live births. The treatment of the large, dark, plate
like scales that characterize the classic manifestation of the disease are still
a challenge. The aim of this study was to evaluate the efficacy and tolerability
of Dr. Michaels(r) skin-care products for the management of LI. A multi-centre
European prospective study was conducted, including 10 patients (3 female/7 male)
with lamellar ichthyosis, aged 38-54 years old (mean age: 46). Each patient had
been treated with emollients plus other different systemic therapies, such as
corticosteroids, Cyclosporin A or retinoids in the past. All patients were
treated with Dr Michaels(r) product family including both topical and oral herbal
supplements. The topical treatments used were the cleansing gel, activator
formula and ointment. The oral medications were PSC 200, PSC 400 and PSC 900.
Within 3 weeks of initiation of treatment, there were improvements observed on
the skin including a reduction in scaling, fissuring, and intensity in erythema
and pruritus with thinning of the hyperkeratotic plate. After 12-15 weeks, most
of the plates and scales had been removed to reveal a normalised skin colour.
Evidence of hair, eyelash and eyebrow growth was observed. There was partial nail
resolution with a reduction in subungual hyperkeratosis. No adverse reactions
were observed. Our patients showed excellent symptomatic response to treatment
within a 14-week period, follow-up by an on-going regular assessment on a
quarterly basis. The results show that Dr Michaels(r) product family is an
effective and safe treatment option for LI.
PMID- 27498661
TI - Investigation of the efficacy of Dr Michaels(r) (Soratinex(r)) family in
maintaining a symptom-free state for patients with psoriasis in remission. A
retrospective, comparative study.
AB - Psoriasis is a chronic inflammatory disease, affecting about 3% of the worldwide
population. Although there are many therapeutic options available today for
psoriasis, none of them can be considered as the gold standard treatment for
maintaining a sustained period of remission. The aim of this study was to
investigate whether a maintenance dosage of Michaels(r) Soratinex(r) product
family is effective in maintaining a symptom-free state for patients in
remission. Fifty patients (23 male, 27 female), aged 18-58-years-old (mean age:
38.3), affected by mild to severe plaque psoriasis (mean duration: 29.5), were
included in this retrospective study. All of them had completed previous
treatment and achieved remission. Twenty-eight had been previously treated with
an Australian series of herbal skin-care products (Dr. Michaels(r) Soratinex(r)
skincare products for psoriasis) and 22 treated with biologics. We evaluated the
clinical condition of the member of each group every 4 weeks, for 16 times
following remission. Maintenance group continued treatment with Dr Michaels(r)
(Soratinex(r)). Non-Maintenance group discontinued both forms of treatment. The
evaluation was based on the PASI score, assuming that at baseline it was zero.
Out of 34 patients who continued treatment with Dr Michaels(r) (Soratinex(r))
product family in the Maintenance group (22 previously treated with Dr Michaels
and 12 previously treated with Biologic), 26 remained symptom free with baseline
PASI of zero. Six patients had a mild flare with a PASI increase of 0-25%. Two
patients were in the moderate group with a PASI increase of 26-50% and were
initially treated with biologic. Out of 6 patients in Dr Michaels non-maintenance
group, 3 patients remained symptom free, 1 had a rebound starting on week 36 and
2 rebounded at week 44. Out of 10 patients who were in the non-maintenance from
the biologic group, 6 rebounded at week 12, 2 rebounded at week 16, 1 rebounded
at week 24 and 1 rebounded at week 32. In the maintenance group no side effects
were described, except for a mild form of folliculitis in 3 patients. Treatment
did not have to be discontinued and all 3 patients cleared. Based on the results
of this study, Dr. Michaels(r) (Soratinex(r)) product family can be safely and
successfully applied to maintain a symptom-free state, after patients go into
remission following treatment with Dr. Michaels(r) (Soratinex(r)) product family
or biologics in mild to very severe psoriasis, when considering the exclusion
criteria.
PMID- 27498662
TI - Dr Michaels(r) product family (also branded as Soratinex(r)) versus
Methylprednisolone aceponate - a comparative study of the effectiveness for the
treatment of plaque psoriasis.
AB - As one of the most common dermatologic chronic-recurrent disease, variable
therapeutic options are available today for management of psoriasis. Although
topical high potency corticosteroids, alone or in association with salicylic acid
or vitamin D analogues, are still considered the best treatment, they do not seem
to possess the capability for a long-term control of the disease or prevent
recurrences, as their side effects are major contraindications for continuative
use. The aim of this study was to investigate whether Dr. Michaels(r) product
family is comparable to methylprednisolone aceponate (MPA) as a viable
alternative treatment option for the treatment and management of stable chronic
plaque psoriasis. Thirty adults (13 male, 17 female, mean age 40 years) with mild
to severe stable chronic plaque psoriasis, were included in the study. Patients
were advised to treat the lesions of the two sides of their body (left and right)
with two different unknown modalities for 8 weeks; the pack of Dr. Michaels(r)
products on the left side (consisting of a cleansing gel, an ointment and a skin
conditioner) and a placebo pack on the right side, consisting of a cleansing gel,
methylprednisolone ointment and a placebo conditioner. Assessment was done using
the Psoriasis Activity Severity Index (PASI) scores before treatment and after 2,
4, 6 and 8 weeks. The results achieved with the Dr. Michaels(r) (Soratinex(r))
product family for the treatment of chronic plaque psoriasis were better than the
results achieved with methylprednisolone aceponate (MPA), even though quicker
resolution was achieved with the steroid with 45% of patients achieving
resolution within 8-10 days in comparison to 5-6 weeks in the Dr. Michaels(r)
(Soratinex(r)) group. Before therapy, the mean PASI score of the LHS in Dr.
Michaels(r) (Soratinex(r)) group was 13.8+/-4.1 SD and 14.2+/-4.2 SD in the RHS
methylprednisolone aceponate (MPA) group. After 8 weeks of treatment 62% of the
Dr. Michaels(r) (Soratinex(r)) group had achieved resolution whilst in the
methylprednisolone aceponate (MPA) group, the figure remained at 45%. The mean
PASI score after 8 weeks of treatment was calculated and in the LHS Dr.
Michaels(r) (Soratinex(r)) group it was 2.8+/-1.6 SD and 6.8+/-2.4 SD in the RHS
methylprednisolone aceponate group. In the RHS -methylprednisolone aceponate
(MPA) group, 22% of patients failed to respond to the treatment in comparison to
6% in the LHS Dr. Michaels(r) (Soratinex(r)) group. Based on the results of this
study, Dr. Michaels(r) products are a more effective treatment option, with
insignificant side effects, compared to local treatment with methylprednisolone
aceponate (MPA).
PMID- 27498663
TI - Successful treatment of alopecia areata with Dr. Michaels(r) (Alopinex) product
family.
AB - Alopecia areata is a highly prevalent organ restricted autoimmune disorder that
leads to disfiguring hair loss and is thought to involve a T cell?mediated
response to the hair follicle. The treatment of alopecia areata is often
problematic and very frustrating, partly due to the unknown aetiology of the
condition. The aim of this study was to evaluate the efficacy and tolerability of
complementary medicine, Dr. Michaels(r) product family, in the treatment of
alopecia areata. MATERIALS AND METHODS: 40 patients (27 female/13 male), with a
mean age of 20.3 years, all of them with 1-3 lesions of stable alopecia areata
localized on the scalp were included in this trial. Four patients suffered from
Hashimoto thyroiditis, and one had a familial history of LES. Exclusion criteria
were the use of any treatment or medication, which may influence or interfere
with the course of the disease. All patients were treated with Dr. Michaels(r)
StimOils - applied twice daily (morning and night), Hair Lotion ? applied twice
daily (morning and night), and oral herbal formulation - PSC 900 2ml twice daily
with food for 16 weeks. For each patient, photographs of typical lesions were
taken at the beginning and at 4, 8, 12 and 16 weeks follow-up. Patient
improvement was determined by the percentage of hair regrowth for each lesion.
RESULTS: After 10 weeks of treatment using StimOils, Hair Lotion and PSC 900 from
Dr. Michaels(r) product family, 18 patients had achieved an excellent response
with regrowth in all the affected alopecia areata patches. 17 patients achieved
the same results after 12 weeks of treatment; the other 5 patients had to
continue the therapeutic protocol for another 2-3 weeks. CONCLUSION: This study
demonstrates that the Dr. Michaels(r) StimOils, Hair Lotion and PSC 900 are an
effective therapeutic option for the treatment of alopecia areata. This has
important implications for resistant cases of alopecia areata where traditional
systemic and topical corticosteroid therapies have failed. In addition, this
treatment approach may be an attractive option for patients who have growing
concern regarding side-effects of long-term corticosteroid therapy.
PMID- 27498664
TI - Successful treatment of recalcitrant candidal intertrigo with Dr Michaels(r)
(Fungatinex(r)) product family.
AB - Candidal intertrigo is an infection of the skin caused by Candida albicans that
typically occurs in opposing cutaneous or muco-cutaneous surfaces. Because
Candidiasis requires a damaged and moist environment for infection, it typically
occurs in areas of friction such as the skin folds of the body. Candidal
intertrigo is often difficult to treat and results are often unsatisfactory. In
addition, there is a lack of evidence-based literature supporting prevention and
treatments for candidal intertrigo. The aim of the study was to evaluate the
efficacy of Dr Michaels(r) (also branded as Fungatinex(r)) products in the
treatment of fungal intertrigo, in 20 women and 2 men with a mean age of 72. Five
patients (3 female and 2 male) had type 2 diabetes and 16 (14 female and 2 male)
were obese. The patients were treated with Dr Michaels(r) (Fungatinex(r))
moisturising bar, topical ointment (twice daily application) and oral herbal
formulation, PSC 200 two tablets twice daily with food. After 2 weeks of
treatment, the lesions had mostly resolved in all patients with only slight
erythema evident. After six weeks of treatment using the moisturising bar,
topical ointment and oral herbal formulations from the Dr Michaels(r)
(Fungatinex(r)) product family, the lesions had totally resolved in 18 patients,
while 4 patients had to continue the therapeutic protocol for another 2 weeks.
Our results demonstrate that the Dr Michaels(r) (Fungatinex(r)) complementary
product family is efficacious in the treatment of recalcitrant candidal
intertrigo. Furthermore, this study highlights that the Dr Michaels(r)
(Fungatinex(r)) product family is fast-acting and well tolerated with no serious
adverse events reported. These data have important implications for resistant
cases of candidal intertrigo where traditional therapies have failed.
PMID- 27498665
TI - Successful treatment of facial systemic lupus erythematosus lesions with Dr
Michaels(r) (Soratinex(r)) product family. A case report.
AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which the
body?s immune system mistakenly attacks healthy tissue. It can affect the skin,
joints, kidneys, brain and other organs. We report the case of a 7-year-old
female patient with facial lesions of SLE since the age of 5. There was no
significant family history and patient had been a healthy child from birth. The
child presented with a malar rash, also known as a butterfly rash, with
distribution over the cheeks but sparing the nasal bridge. This case represents
the efficacy of the Dr. Michaels(r) (Soratinex(r)) product family in the
successful resolution of facial lesions of SLE.
PMID- 27498666
TI - Scalp psoriasis: a promising natural treatment.
AB - Psoriasis is a lifelong chronic inflammatory disease affecting 2-3% of the
worldwide population. Scalp psoriasis is a particular form of psoriasis
characterized by lesions on the scalp, which may occur isolated or in association
with other skin lesions. The aim of this study was to investigate the efficacy
and safeness of an innovative treatment of scalp psoriasis, which is based on the
topical application of natural products. Fifty adult subjects with scalp
psoriasis (23 females, 27 males) from different European dermatological centres
were included in the study. Forty-six patients with severely infiltrated
psoriatic lesions were invited to use the products of Dr Michaels(r)
(Soratinex(r)), according to a three-phase application, twice a day (morning and
evening). The other 4 patients followed a different regimen: after a shampoo in
the evening, they applied the conditioner in the night and washed it in the
morning with the cleansing gel. The application time of Dr Michaels(r)
(Soratinex(r)) products was 8 weeks. The treatment was evaluated at 0, 1, 2, 3,
4, 5, 6, 7, and 8 weeks. The evaluation was based on the Psoriasis Scalp Severity
Index (PSSI) and on a photographic analysis at each of the medical evaluation
points. At the end of the study, all patients showed an outstanding improvement.
Five patients referred a transient pruritus, which regressed spontaneously
without discontinuing the application. No other side effects have been described.
We observe that Dr Michaels(r) (Soratinex(r)) natural product family can be
considered as a valid therapeutic tool for scalp psoriasis when considering the
exclusion criteria. The tested products provided an outstanding improvement of
lesions in all the patients, without side effects.
PMID- 27498667
TI - An innovative, promising topical treatment for psoriasis: a Romanian clinical
study.
AB - Psoriasis is a chronic inflammatory disease with negative impacts both physically
and psychologically. It is a common disorder affecting 2-3% of the total world
population, in some cases causing changes to the nail and joints as well as skin
lesions. The cutaneous manifestations of psoriasis can vary in morphology and
severity and therapy should be tailored accordingly. Even if today many
therapeutic options are available for psoriasis treatment, none of them provide
excellent clinical results without the risk of side effects. The authors
investigate the efficacy of Dr. Michaels(r) (Soratinex(r)) natural products in
the topical treatments of a group of psoriatic patients. Sixty-two patients (34
male/28 female) from Romania, aged 18-70 years (mean age: 52 years), affected by
a mild to severe form of chronic plaque psoriasis were included in this study.
Each patient has been treated with a triphasic application of Dr. Michaels(r)
(Soratinex(r)) natural products, twice a day for six weeks. The products were
applied on skin and scalp lesions, but not on the face, genital and flexures. The
evaluation of the tested products was based on the PASI of each patient at time
0, 1, 2, 3, 4, 5, and 6 weeks. The tested products were ineffective in five of 57
patients. Eleven patients had a moderate improvement (PASI decrease 26-50%); 11
patients had a good improvement (PASI decrease 51-75%) and 30 patients an
outstanding one (PASI decrease 76-100%). Twenty-three% of patients developed
folliculitis that regressed upon discontinuation of the application. Five
patients developed pruritus, which regressed spontaneously. The cosmetic effect
was evaluated as indifferent by 44% of patients, as good by 40% of patients and
as excellent by 16% of patients. Ninety-five% of patients stated that they would
continue to use the tested products, because it was effective and with poor side
effects since the products were natural. In our experimental study, the topical
application of Dr. Michaels(r) (Soratinex(r)) natural products proved to be an
effective natural therapeutic option for psoriasis treatment.
PMID- 27498668
TI - Efficacy and safety of Dr Michaels(r) (Soratinex(r)) product family for the
topical treatment of psoriasis: a monitored status study.
AB - The aim of the study was to investigate the efficacy and safety of Michaels(r)
(Soratinex(r)) remedies in patients suffering from chronic plaque psoriasis in a
Czech population. Seventy-five (34 female/41 male) patients, aged 18-72 years old
(mean age: 38.5 years) with mild to severe plaque psoriasis participated in the
study. The products, including cleansing gel, ointment and skin conditioner,
containing fruit acid complex, herbal oils and emulsifiers, were used twice daily
and in the same manner for all the skin lesions. The study period was eight
weeks. Histologic variables and various blood picture parameters, including FW,
glucose, cholesterol, triacylglyceroles, bilirubin, GMT, ALT, AST, creatinine,
uric acid and urea in blood were monitored, before and after therapy with
Michaels(r) (Soratinex(r)) treatment. Assessment, using the Psoriasis Activity
Severity Index (PASI) scores and photographic analysis, was done at time 0, and
after 2, 4, 6 and 8 weeks. Patient?s improvement was determined by the percentage
reduction of the PASI scores. Side effects and tolerability were also evaluated.
After 8 weeks using Dr Michaels(r) (Soratinex(r)) treatment course, 5 patients
had a moderate improvement, with the resolution of 25-50% of skin lesions; 11
patients showed a good improvement, with the resolution of 51-75% of lesions.
Another 50 patients had an outstanding improvement, with the regression of 76
100% of lesions. Only 4 patients did not achieve an improvement of psoriasis. Six
patients experienced folliculitis, which resolved without cessation of treatment.
Three patients worsened and discontinued treatment. Six patients dropped out
because of non-compliance. The blood results and histologic findings were all
normal. Our investigation shows that Dr Michaels(r) (Soratinex(r)) products can
be safely and successfully used in the treatment of chronic plaque psoriasis.
PMID- 27498669
TI - Quality of life aspects of patients with psoriasis using a series of herbal
products.
AB - Psoriasis is a chronic inflammatory disease affecting 1-3% of the general
population. Due to the chronic nature of the disease, patients suffer from
substantial psychosocial impact and impaired quality of life. Dr Michaels(r)
(also branded as Soratinex(r)), an Australian series of topical herbal products,
has been showing promising results for the treatment of patients with chronic
plaque psoriasis and consequent improvement in their quality of life. This study
aims to access the changes in quality of life of patients with Psoriasis using an
Australian series of herbal skin-care products Dr Michaels(r) (Soratinex(r)) for
psoriasis. The aim of this study is to observe and analyze the impact of Dr
Michaels(r) product family on the quality of life of patients with psoriasis, 566
patients completed the Dermatology Quality of Life Index (DQLI) questionnaire in
their initial consultation and at 3 follow up consultations, over a 6 months
period. At the end of the data collection, all patients? answers were recorded
and analyzed. The Psoriasis Area and Severity (PASI) Index were used to measure
the severity and extent of psoriasis during the 3 consultations. The PASI for
severe, moderate-severe, mild-moderate cases across time revealed a significant
effect of the treatment within weeks, confirming the decreasing scores during the
treatment. As well as PASI results, the final DLQI score showed a sensible
reduction from mean =6.716 (at week 0) to 6.252 (at week 2), 4.015 (at week 6)
and 2.407 (at week 10) signifying a 64.2% reduction of the initial score. This
study demonstrates that Dr. Michaels(r) (Soratinex(r)) products, an Australian
series of herbal-based skin products is effective for the treatment of psoriasis.
This treatment also significantly improves patient?s quality of life.
PMID- 27498670
TI - Rapid communication: a vegetable oil extract restores redox status in fibroblasts
from psoriatic patients.
AB - Psoriasis is an inflammatory skin disease that affects 2-5% of the worldwide
population. It is a chronic immune-mediated hyperproliferative inflammatory skin
disease of unknown etiology, characterized by the appearance of sore patches of
thick, red skin with silvery scales.
PMID- 27498671
TI - The power of two: an update on fixed-dose combinations for type 2 diabetes.
AB - INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) are unlikely to
maintain glycemic control with monotherapy, and will eventually require therapy
with multiple antihyperglycemic agents (AHAs). Combination therapy regimens with
multiple AHAs may be complex and negatively impact patient adherence. Fixed-dose
combinations (FDCs) are used successfully for management of numerous chronic
diseases. Areas covered: This article includes a brief overview of the add-on
approach of current treatment guidelines for T2DM and reviews the evidence
supporting the utility of oral FDCs in the treatment of T2DM, including recently
developed oral FDCs (2010-2016). Benefits regarding safety and tolerability,
adherence and cost are also discussed. Finally, the barriers limiting the use of
FDCs and how these barriers may be overcome are addressed. Expert commentary:
Therapeutic strategies including FDCs need to be implemented on a larger scale.
FDCs have the potential to simplify treatment regimens, improve adherence and
provide long-term glycemic control.
PMID- 27498672
TI - Epigenetically deregulated miR-200c is involved in a negative feedback loop with
DNMT3a in gastric cancer cells.
AB - Aberrant methylation of miRNAs is commonly observed in cancers. In the present
study, we investigated the regulation of the miR-200 family and its role in
regulating DNA methylation events in gastric cancer (GC). We demonstrated that
miR-200c was aberrantly expressed in GC and associated with histologic type and
tumor progression. Hypermethylation of the promoter region was found to be
responsible for the loss of miR-200c in GC cells. Demethylation agents led to
recovery of miR-200c expression in GC cell lines. Moreover, DNMT3a knockdown
abolished the hypermethylation of the miR-200c gene and induced upregulation of
miR-200c expression, whereas ectopic DNMT3a expression increased miR-200c
promoter methylation and decreased miR-200c expression. Conversely, transfection
of miR-200c led to downregulation of DNMT3a protein and induced endogenous pre
miR-200c and pri-miR-200c re-expression. Luciferase assays confirmed miR-200c
binding to the DNMT3a 3'UTR. Finally, ectopic expression of miR-200c or knockdown
of DNMT3a expression impeded GC cell growth, migration and invasion. Taken
together, these observations demonstrates a novel epigenetic feedback loop
between miR-200c and DNMT3a in the carcinogenesis and progression of GC.
PMID- 27498673
TI - Oleuropein inhibits the proliferation and invasion of glioma cells via
suppression of the AKT signaling pathway.
AB - Oleuropein, the main phenolic compound of secoiridoids, has been proven to have
inhibitory effects on various types of cancers. However, the antitumor effects
and related mechanisms in glioma remain unclear. In the present study, U251 and
A172 cells were used to assess the effects of oleuropein. Using cell viability
assay, we found that oleuropein greatly inhibited the viability of the U251 and
A172 cells. Additionally, flow cytometric apoptosis assay indicated that
oleuropein induced the apoptosis of the two cell lines. Consistently, the
inhibitory effects of oleuropein on migration and invasion were also observed in
vitro. In regards to the mechanism, we found that oleuropein significantly
decreased phosphorylation of AKT (p-AKT), accompanied by upregulation of Bax and
downregulation of Bcl-2. We also found that there was a decrease in the
expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 after treatment
with oleuropein. Furthermore, a specific phosphatidylinositol 3 kinase (PI3K)
inhibitor, LY294002, enhanced the pro-apoptotic and anti-invasive effects induced
by oleuropein, which suggested that oleuropein suppressed the growth and invasion
of glioma cells via inhibition of AKT activity. Taken together, our results
indicated that treatment with oleuropein may be an effective therapy for
malignant glioma through suppression of tumor proliferation and invasion by
inhibition of the AKT signaling pathway.
PMID- 27498674
TI - Severe Infections are Common in Thiamine Deficiency and May be Related to
Cognitive Outcomes: A Cohort Study of 68 Patients With Wernicke-Korsakoff
Syndrome.
AB - BACKGROUND: Wernicke encephalopathy can have different clinical outcomes.
Although infections may precipitate the encephalopathy itself, it is unknown
whether infections also modify the long-term outcome in patients developing
Korsakoff syndrome. OBJECTIVE: To determine whether markers of infection, such as
white blood cell (WBC) counts and absolute neutrophil counts in the Wernicke
phase, are associated with cognitive outcomes in the end-stage Korsakoff
syndrome. METHOD: Retrospective, descriptive study of patients admitted to
Slingedael Korsakoff Center, Rotterdam, The Netherlands. Hospital discharge
letters of patients with Wernicke encephalopathy were searched for relevant data
on infections present upon hospital admission. Patients were selected for further
analysis if data were available on WBC counts in the Wernicke phase and at least
1 of 6 predefined neuropsychological tests on follow-up. RESULTS: Infections were
reported in 35 of 68 patients during the acute phase of Wernicke-Korsakoff
syndrome-meningitis (1), pneumonia (14), urinary tract infections (9), acute
abdominal infections (4), sepsis (5) empyema, (1) and infection "of unknown
origin" (4). The neuropsychological test results showed significant lower scores
on the Cambridge Cognitive Examination nonmemory section with increasing white
blood cell counts (Spearman rank correlation, rho = -0.34; 95% CI: -0.57 to
0.06; 44 patients) and on the "key search test" of the behavioral assessment of
the dysexecutive syndrome with increasing absolute neutrophil counts (rho= -0.85;
95% CI: -0.97 to -0.42; 9 patients). CONCLUSIONS: Infections may be the
presenting manifestation of thiamine deficiency. Patients with Wernicke-Korsakoff
syndrome who suffered from an infection during the acute phase are at risk of
worse neuropsychological outcomes on follow-up.
PMID- 27498675
TI - All-cause mortality risk as a function of sedentary behavior, moderate-to
vigorous physical activity and cardiorespiratory fitness.
AB - OBJECTIVE: Emerging work demonstrates individual associations of sedentary
behavior, moderate-to-vigorous physical activity (MVPA) and cardiorespiratory
fitness (CRF) on mortality risk. Limited research has evaluated all three of
these parameters in a model when considering mortality risk, and their potential
additive association on mortality risk has not been fully evaluated, which was
the purpose of this study. METHODS: Data from the 2003-2006 National Health and
Nutrition Examination Survey were used (N = 2,295 adults 20-85 yrs), with follow
up through 2011. Sedentary behavior and MVPA were objectively assessed
(accelerometry) with cardiorespiratory estimated from a prediction equation
taking into consideration participant demographic, anthropometric and behavioral
characteristics. Using the median values, a PACS (Physical Activity
Cardiorespiratory Sedentary) score was created that ranged from 0-3, indicating
the number of these three positive characteristics. RESULTS: Those with below
median sedentary behavior did not have a reduced all-cause mortality risk (HR =
0.59; 95% CI: 0.34-1.04; P = 0.07), but those with above median MVPA (HR = 0.35;
95% CI: 0.15-0.82; P = 0.02) and above median CRF did (HR = 0.20; 95% CI: 0.09
0.43; P < 0.001). Compared to those with a PACS score of 0, those with a PACS
score of 1, 2, and 3, respectively, had a 67% (HR = 0.33; 95% CI: 0.17-0.63, P =
0.002), 82% (HR = 0.12; 95% CI: 0.05-0.30; P < 0.001) and 96% (HR = 0.04; 95% CI:
0.02-0.11; P < 0.001) reduced risk of all-cause mortality. CONCLUSION:
Cardiorespiratory fitness and MVPA, but not sedentary behavior, were
independently associated with reduced mortality risk. Adults with all three
characteristics (below median sedentary and above median MVPA and CRF), however,
had the lowest mortality risk.
PMID- 27498676
TI - Editorial: Optimizing Chronic Heart Failure Care Beyond Randomised Controlled
Trials - What are the problem areas and potential solutions?
PMID- 27498677
TI - Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and
Severe Lung Disease.
AB - BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative,
opportunistic pathogen that can be responsible for various severe nosocomial and
community-acquired infections. It has been found in immunocompromised patients
and patients with several other underlying conditions, but the clinical role of
this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case
of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic
fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A.
xylosoxidans in cystic fibrosis patients is rising and patient-to-patient
transmission is highly probable, further studies are warranted to determine its
role and to document the appropriate treatment strategy for eradication and long
term treatment of this organism.
PMID- 27498678
TI - [Retracted] Systemic delivery of synthetic microRNA-451 is an effective
therapeutic strategy for the treatment of lung cancer.
AB - Following the publication of this article, an interested reader drew to our
attention that Figs. 3B and 4B contained histological data which had previously
been published in Figs. 3B and 4B, respectively, of the following article:
Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D and Bader AG:
Development of a lung cancer therapeutic based on the tumor suppressor microRNA
34. Cancer Res. 15: 5923-5930, 2010. We have tried to contact the authors of the
above paper on several occasions for comment, but without success; therefore, the
Editorial Board of the International Journal of Molecular Medicine has taken the
decision to retract this publication. We thank the reader for drawing this matter
to our attention. [the original article was published in the International
Journal of Molecular Medicine 35: 1369-1373, 2015; DOI: 10.3892/ijmm.2015.2147].
PMID- 27498679
TI - Rodent Models of Vascular Cognitive Impairment.
AB - Vascular cognitive impairment dementia (VCID), which is an increasingly important
cause of dementia in the elderly, lacks effective treatments. Many different
types of vascular disease are included under the diagnosis of VCID, including
large vessel disease with multiple strokes and small vessel disease with lacunar
infarcts and white matter disease. Animal models have been developed to study the
multiple forms of VCID. Because of its progressive course, small vessel disease
(SVD) is thought to be the optimal form of VCID for treatment. One theory is that
the pathophysiology involves hypoxic hypoperfusion resulting in injury to the
white matter and neuronal death. Bilateral occlusion of the common carotid
arteries (BCAO) in a normotensive rat, which reduces cerebral blood flow, induces
hypoxia with white matter damage; this model has been used to test drugs to block
the injury. Another model is the spontaneously hypertensive/stroke prone rat
(SHR/SP). Hypertension leads to small vessel disease resulting in progressive
damage to the white matter, cortex, and hippocampus. Bilateral carotid artery
stenosis (BCAS) with coils or ameroid constrictors produces a slower development
of changes than BCAO, avoiding the acute ischemia. A few studies have been done
with the two-clip, two-vessel occlusion renal model for induction of
hypertension. There are benefits and drawbacks to each of these models with the
model selected depending on the type of vascular damage that is to be studied.
This review describes the most commonly used models, and the drugs that have been
used to reduce the damage.
PMID- 27498681
TI - Erratum to: Genetic Counselling for Psychiatric Disorders: Accounts of
Psychiatric Health Professionals in the United Kingdom.
PMID- 27498680
TI - How to Measure Recovery? Revisiting Concepts and Methods for Stroke Studies.
AB - In clinical trials, assessing efficacy is based on validated scales, and the
primary endpoint is usually based on a single scale. The aim of the review is to
revisit the concepts and methods to design and analyze studies focused on
restoration, recovery and or compensation. These studies are becoming more
frequent with the development of restorative medicine. After discussing the
definitions of recovery, we address the concept of recovery as the regain of lost
capabilities, when the patient reaches a new equilibrium. Recovery is a dynamic
process which assessment includes information from initial and final status,
their difference, the difference between the final status of the patient and
normality, and the speed of restoration. Finally, recovery can be assessed either
for a specific function (focal restoration) or for a more global restoration. A
single scale is not able to assess all the facets of a skill or a function,
therefore complementary information should be collected and analyzed
simultaneously to be tested in a single analysis. We are suggesting that recovery
should be considered as a latent variable and therefore cannot be measured in
pure form. We are also suggesting to customize the data collection and analysis
according to the characteristics of the subjects, the mechanisms of action and
consequences of the intervention. Moreover, recovery trials should benefit from
latent variable analysis methods. Structural equation modeling is likely the best
candidate for this approach applicable in pre-clinical and clinical studies.
PMID- 27498682
TI - A novel variant of androgen receptor is associated with idiopathic azoospermia.
AB - A variety of genetic variants can lead to abnormal human spermatogenesis. The
androgen receptor (AR) is an important steroid hormone receptor that is critical
for male sexual differentiation and the maintenance of normal spermatogenesis. In
the present study, each exon of AR in 776 patients diagnosed with idiopathic
azoospermia (IA) and 709 proven fertile men were sequenced using use panel re
sequencing methods to examine whether AR is involved in the pathogenesis of IA.
Two synonymous variants and seven missense variants were detected. Of the
missense variants, a luciferase assay demonstrated that the R630W variant reduced
the transcriptional regulatory function of AR. This novel variant (p. R630W) of
AR is the first to be identified in association with IA, thereby highlighting the
importance of AR during spermatogenesis.
PMID- 27498683
TI - Ultrasonography and contrast-enhanced CT findings of tularemia in the neck.
AB - PURPOSE: We aimed to evaluate the ultrasonography (US) and contrast-enhanced
computed tomography (CECT) findings of tularemia in the neck. METHODS: US and
CECT findings of 58 patients with serologically proven tularemia were
retrospectively evaluated. Forty-eight patients underwent US and 42 patients
underwent CECT. Lymph node characteristics and parotid preauricular region
involvement were analyzed using US and CECT. In addition, involvement of larynx,
oropharynx, and retropharynx; presence of periorbital edema; and neck abscess
formation were evaluated using CECT. Fine needle aspiration cytology (FNAC)
results of enlarged lymph nodes were analyzed in 29 patients. RESULTS: Hypoechoic
pattern, round shape, absence of hilum, and cystic necrosis were seen in most of
the lymph nodes especially at level 2 and 3 on US and CECT. Matting was more
commonly observed than irregular nodal border on US and CECT. Parotid
preauricular region involvement was seen in 20.8% of patients on US.
Oropharyngeal, retropharyngeal, laryngeal and parotid preauricular region
involvement and periorbital edema were seen in 52.4%, 19.1%, 4.8%, 31%, and 9.5%
of tularemia patients, respectively. Neck abscess was found in 59.5% of patients
on CECT. Suppurative inflammation was the most common finding of FNAC.
CONCLUSION: Tularemia should be considered in the presence of level 2 and 3 lymph
nodes with cystic necrosis, matting, absence of calcification, oropharyngeal and
retropharyngeal region involvement, and neck abscess, particularly in endemic
areas.
PMID- 27498686
TI - Charge transfer reactions between gas-phase hydrated electrons, molecular oxygen
and carbon dioxide at temperatures of 80-300 K.
AB - The recombination reactions of gas-phase hydrated electrons (H2O)n(-) with CO2
and O2, as well as the charge exchange reaction of CO2(-)(H2O)n with O2, were
studied by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry
in the temperature range T = 80-300 K. Comparison of the rate constants with
collision models shows that CO2 reacts with 50% collision efficiency, while O2
reacts considerably slower. Nanocalorimetry yields internally consistent results
for the three reactions. Converted to room temperature condensed phase, this
yields hydration enthalpies of CO2(-) and O2(-), DeltaHhyd(CO2(-)) = -334 +/- 44
kJ mol(-1) and DeltaHhyd(O2(-)) = -404 +/- 28 kJ mol(-1). Quantum chemical
calculations show that the charge exchange reaction proceeds via a CO4(-)
intermediate, which is consistent with a fully ergodic reaction and also with the
small efficiency. Ab initio molecular dynamics simulations corroborate this
picture and indicate that the CO4(-) intermediate has a lifetime significantly
above the ps regime.
PMID- 27498687
TI - Genetic and clinical characteristics of Japanese patients with sporadic
somatotropinoma.
AB - Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel
gene mutations responsible for somatotropinoma have recently been reported. To
determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed
61 consecutive Japanese patients with somatotropinoma without apparent family
history. Comprehensive genetic analysis revealed that 31 patients harbored
guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%)
and three patients harbored aryl hydrocarbon receptor interacting protein (AIP)
mutations (4.9%). No patients had G protein-coupled receptor 101 (GPR101)
mutations. The patients in this cohort study were categorized into three groups
of AIP, GNAS, and others and compared the clinical characteristics. The AIP group
exhibited significantly younger age at diagnosis, larger tumor, and higher nadir
GH during oral glucose tolerance test. In all patients with AIP mutation, macro-
and invasive tumor was detected and repetitive surgery or postoperative medical
therapy was needed. One case showed a refractory response to postoperative
somatostatin analogue (SSA) but after the addition of cabergoline as combined
therapy, serum IGF-I levels were controlled. The other case showed a modest
response to SSA and the switching to cabergoline monotherapy was also effective.
These data suggest that although resistance to SSA has been reported in patients
with AIP mutations, the response to dopamine agonist (DA) may be retained. In
conclusion, the cause of sporadic somatotropinoma in Japanese patients was
comparable with the previous reports in Caucasians, patients with AIP mutations
showed unique clinical characteristics, and DA may be a therapeutic option for
patients with AIP mutations.
PMID- 27498685
TI - Multiple independent transmission cycles of a tick-borne pathogen within a local
host community.
AB - Many pathogens are maintained by multiple host species and involve multiple
strains with potentially different phenotypic characteristics. Disentangling
transmission patterns in such systems is often challenging, yet investigating how
different host species contribute to transmission is crucial to properly assess
and manage disease risk. We aim to reveal transmission cycles of bacteria within
the Borrelia burgdorferi species complex, which include Lyme disease agents. We
characterized Borrelia genotypes found in 488 infected Ixodes ricinus nymphs
collected in the Senart Forest located near Paris (France). These genotypes were
compared to those observed in three sympatric species of small mammals and
network analyses reveal four independent transmission cycles. Statistical
modelling shows that two cycles involving chipmunks, an introduced species, and
non-sampled host species such as birds, are responsible for the majority of tick
infections. In contrast, the cycle involving native bank voles only accounts for
a small proportion of infected ticks. Genotypes associated with the two primary
transmission cycles were isolated from Lyme disease patients, confirming the
epidemiological threat posed by these strains. Our work demonstrates that
combining high-throughput sequence typing with networks tools and statistical
modeling is a promising approach for characterizing transmission cycles of multi
host pathogens in complex ecological settings.
PMID- 27498688
TI - Autophagic degradation of epidermal growth factor receptor in gefitinib-resistant
lung cancer by celastrol.
AB - Drug resistance of non-small cell lung cancer (NSCLC) is highly correlated to the
mutation of the epidermal growth factor receptor (EGFR). Although EGFR tyrosine
kinase inhibitors (TKIs) are available clinically, the molecular complexity of
NSCLC has made it necessary to search for alternative therapeutic approaches to
overcome the drug resistance of NSCLC. In the present study, we identified a
triterpene molecule derived from the herbal plant Tripterygium wilfordii,
celastrol, as a novel autophagy inducer. We demonstrate that celastrol exhibited
selective cytotoxic effect towards EGFR mutant NSCLCs. In addition, celastrol
also facilitated the autophagic degradation of Hsp90 client protein including
EGFR and Akt on both EGFR wild-type and mutant NSCLCs via calcium-mediated
autophagy. Blockage of celastrol-induced autophagic degradation of EGFR by
autophagic inhibitor or calcium chelator decreased celastrol-mediated cell death
in gefitinib-resistant NSCLCs. Overall, our findings suggest that celastrol may
be developed as an effective anticancer agent for treatment of gefitinib
resistant NSCLC in the future.
PMID- 27498689
TI - Spin-glass behavior and pyroelectric anomalies in a new lithium-based oxide,
Li3FeRuO5.
AB - The results of dc and ac magnetization, heat capacity, (57)Fe Mossbauer
spectroscopy, dielectric, pyroelectric current and isothermal magneto-capacitance
measurements of a recently reported lithium-rich layered oxide, Li3FeRuO5,
related to LiCoO2-type (rhombohedral, space group R3[combining macron]m), are
presented. The results reveal that the compound undergoes spin-glass freezing at
15 K. There is a peak around 34 K in pyroelectric data, which cannot be
attributed to ferroelectricity, but to the phenomenon of thermally stimulated
depolarization current. As revealed by magnetocapacitance data above and below
the magnetic ordering temperature, magnetic and electric dipoles appear to be
coupled, thereby offering evidence for magnetodielectric coupling.
PMID- 27498690
TI - A novel transformation route from PbS to CH3NH3PbI3 for fabricating curved and
large-area perovskite films.
AB - We present a new transformation route from PbS to CH3NH3PbI3 for the facile
preparation of perovskites with all kinds of shapes via vapor-assisted chemical
bath deposition (VACBD). As such, curved and large-area CH3NH3PbI3 films with
high quality are successfully achieved, which are suitable for the manufacturing
scale-up of perovskite solar cells.
PMID- 27498691
TI - Genetic screen: A network to guide precision cancer therapy.
PMID- 27498694
TI - Iridium-based double perovskites for efficient water oxidation in acid media.
AB - The development of active, cost-effective and stable oxygen-evolving catalysts is
one of the major challenges for solar-to-fuel conversion towards sustainable
energy generation. Iridium oxide exhibits the best available compromise between
catalytic activity and stability in acid media, but it is prohibitively expensive
for large-scale applications. Therefore, preparing oxygen-evolving catalysts with
lower amounts of the scarce but active and stable iridium is an attractive avenue
to overcome this economical constraint. Here we report on a class of oxygen
evolving catalysts based on iridium double perovskites which contain 32 wt% less
iridium than IrO2 and yet exhibit a more than threefold higher activity in acid
media. According to recently suggested benchmarking criteria, the iridium double
perovskites are the most active catalysts for oxygen evolution in acid media
reported until now, to the best of our knowledge, and exhibit similar stability
to IrO2.
PMID- 27498695
TI - Surface modification of adamantane-terminated gold nanoclusters using
cyclodextrins.
AB - The surface functionality of Au38S2(SAdm)20 nanoclusters (-SAdm =
adamantanethiolate) in the presence of alpha-, beta-, and gamma-cyclodextrins
(CDs) is studied. The supramolecular chemistry and host-guest interactions of CDs
and the protecting ligands of nanoclusters are investigated using UV-vis and NMR
spectroscopies, MALDI mass spectrometry, and molecular dynamics simulations. In
contrast to alpha- and gamma-CDs, the results show that beta-CDs are capable of
efficiently chemisorbing onto the Au38S2(SAdm)20 nanoclusters to yield
Au38S2(SAdm)20-(beta-CD)2 conjugates. MD simulations revealed that two -SAdm
ligands of the nanoparticle with the least steric hindrance are capable to
selectively be accommodated into hydrophobic cavity of beta-CDs, as furthermore
confirmed by NMR spectroscopy. The conjugates largely improve the stability of
the nanoclusters in the presence of strong oxidants (e.g., TBHP). Further, the
electrochemical properties of Au38S2(SAdm)20 nanoclusters and Au38S2(SAdm)20
(beta-CD)2 conjugates are compared. The charge transfer to the redox probe
molecules (e.g., K3Fe(CN)6) in solution was monitored by cyclic voltammetry. It
is found that beta-CDs act as an umbrella to cover the fragile metal cores of the
nanoclusters, thereby blocking direct interaction with destabilizing agents and
hence quenching the charge transfer process.
PMID- 27498693
TI - Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of
TLR induced M1 and K63 ubiquitin chain formation.
AB - Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved
for the treatment of psoriasis and multiple sclerosis. While clinically
effective, its molecular target has remained elusive - although it is known to
activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory
cytokine production in response to TLR agonists independently of the Nrf2-Keap1
anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating
enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in
cells. The formation of K63 and M1 chains is required to link TLR activation to
downstream signaling, and consistent with the block in K63 and/or M1 chain
formation, DMF inhibits NFkappaB and ERK1/2 activation, resulting in a loss of
pro-inflammatory cytokine production. Together these results reveal a new
molecular target for DMF and show that a clinically approved drug inhibits M1 and
K63 chain formation in TLR induced signaling complexes. Selective targeting of
E2s may therefore be a viable strategy for autoimmunity.
PMID- 27498692
TI - Network biology concepts in complex disease comorbidities.
AB - The co-occurrence of diseases can inform the underlying network biology of shared
and multifunctional genes and pathways. In addition, comorbidities help to
elucidate the effects of external exposures, such as diet, lifestyle and patient
care. With worldwide health transaction data now often being collected
electronically, disease co-occurrences are starting to be quantitatively
characterized. Linking network dynamics to the real-life, non-ideal patient in
whom diseases co-occur and interact provides a valuable basis for generating
hypotheses on molecular disease mechanisms, and provides knowledge that can
facilitate drug repurposing and the development of targeted therapeutic
strategies.
PMID- 27498696
TI - The suppression of scale-free fMRI brain dynamics across three different sources
of effort: aging, task novelty and task difficulty.
AB - There is growing evidence that fluctuations in brain activity may exhibit scale
free ("fractal") dynamics. Scale-free signals follow a spectral-power curve of
the form P(f ) ? f(-beta), where spectral power decreases in a power-law fashion
with increasing frequency. In this study, we demonstrated that fractal scaling of
BOLD fMRI signal is consistently suppressed for different sources of cognitive
effort. Decreases in the Hurst exponent (H), which quantifies scale-free signal,
was related to three different sources of cognitive effort/task engagement: 1)
task difficulty, 2) task novelty, and 3) aging effects. These results were
consistently observed across multiple datasets and task paradigms. We also
demonstrated that estimates of H are robust across a range of time-window sizes.
H was also compared to alternative metrics of BOLD variability (SDBOLD) and
global connectivity (Gconn), with effort-related decreases in H producing similar
decreases in SDBOLD and Gconn. These results indicate a potential global brain
phenomenon that unites research from different fields and indicates that fractal
scaling may be a highly sensitive metric for indexing cognitive effort/task
engagement.
PMID- 27498697
TI - Expression pattern and methylation of estrogen receptor alpha in breast
intraductal proliferative lesions.
AB - Intraductal proliferative lesions of the breast including usual ductal
hyperplasia (UDH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ
(DCIS) are associated with increased risk, albeit of greatly different
magnitudes, for the subsequent development of invasive carcinoma. Estrogen
receptor alpha (ERalpha) has been widely accepted as a prognostic marker and a
predictor for endocrine therapy response of breast cancer. To investigate the
ERalpha expression and methylation in breast intraductal proliferative lesions,
we analyzed ERalpha expression in breast intraductal proliferative lesions
including pure UDH (N=98), ADH without DCIS (N=160), DCIS without invasive breast
cancer (N=149) by immunohistochemistry. Furthermore, the methylation status of
ERalpha by methylation-specific PCR (MSP) was defined in 217 cases of breast
intraductal proliferative lesions. Immunohistochemistry showed that 98/98 (100%)
of the UDH cases were positive for ERalpha expression. ERalpha protein expression
in ADH (132/160) (92.5%) was higher than in DCIS (101/149) (67.8%). But the
ERalpha expression pattern was different with histological diversity of breast
intraductal proliferative lesions. The average percent cells staining positive
for ERalpha was 35.33% in UDH, 87.75% in ADH and 71.45% in DCIS. ERalpha
methylation in 32/60 (53.3%) UDH, 11/77 (10.2%) ADH and 32/80 (40.0%) DCIS. Our
results demonstrated a strong negative correlation between the percent of cells
staining positive for ERalpha and ERalpha methylation (r=-0.831, p<0.001). Taken
together, our results underlined that ERalpha expression or methylation may be
involved in the breast carcinogenesis and advancement, thus it is not parallel to
breast cancer risk in breast intraductal proliferative lesions. No obvious
watershed between ERalpha-positive and -negative breast carcinogenesis was
established. Estrogen receptor (ER) methylation or expression is a reversible
signal in breast carcinogenesis which affected biological behavior of cells.
PMID- 27498698
TI - Nanoscale Structure, Dynamics, and Aging Behavior of Metallic Glass Thin Films.
AB - Scanning tunnelling microscopy observations resolve the structure and dynamics of
metallic glass Cu100-xHfx films and demonstrate scanning tunnelling microscopy
control of aging at a metallic glass surface. Surface clusters exhibit
heterogeneous hopping dynamics. Low Hf concentration films feature an aged
surface of larger, slower clusters. Argon ion-sputtering destroys the aged
configuration, yielding a surface in constant fluctuation. Scanning tunnelling
microscopy can locally restore the relaxed state, allowing for nanoscale
lithographic definition of aged sections.
PMID- 27498699
TI - Suppression of superconductivity and structural phase transitions under pressure
in tetragonal FeS.
AB - Pressure is a powerful tool to study iron-based superconductors. Here, we report
systematic high-pressure transport and structural characterizations of the newly
discovered superconductor FeS. It is found that superconductor FeS (tetragonal)
partly transforms to a hexagonal structure at 0.4 GPa, and then completely
transforms to an orthorhombic phase at 7.4 GPa and finally to a monoclinic phase
above 9.0 GPa. The superconducting transition temperature of tetragonal FeS was
gradually depressed by pressure, different from the case in tetragonal FeSe. With
pressure increasing, the S-Fe-S angles only slightly change but the anion height
deviates farther from 1.38 A. This change of anion height, together with the
structural instability under pressure, should be closely related to the
suppression of superconductivity. We also observed an anomalous metal
semiconductor transition at 6.0 GPa and an unusual increased resistance with
further compression above 9.6 GPa. The former can be ascribed to the tetragonal
orthorhombic structural phase transition, and the latter to the electronic
structure changes of the high-pressure monoclinic phase. Finally, a phase diagram
of tetragonal FeS as functions of pressure and temperature was mapped out for the
first time, which will shed new light on understanding of the structure and
physics of the superconducting FeS.
PMID- 27498700
TI - ZCF32, a fungus specific Zn(II)2 Cys6 transcription factor, is a repressor of the
biofilm development in the human pathogen Candida albicans.
AB - As a human fungal pathogen, Candida albicans can cause a wide variety of disease
conditions ranging from superficial to systemic infections. Many of these
infections are caused by an inherent ability of the pathogen to form biofilms on
medical devices resulting in high mortality. Biofilms formed by C. albicans are a
complex consortium of yeast and hyphal cells embedded in an extracellular matrix
and are regulated by a network of transcription factors. Here, we report the role
of a novel Zn(II)2-Cys6 binuclear cluster transcription factor, ZCF32, in the
regulation of biofilm formation. Global transcriptome analysis reveals that
biofilm development is the most altered pathway in the zcf32 null mutant. To
delineate the functional correlation between ZCF32 and biofilm development, we
determined the set of genes directly regulated by Zcf32. Our data suggests that
Zcf32 regulates biofilm formation by repressing the expression of adhesins,
chitinases and a significant number of other GPI-anchored proteins. We establish
that there is the lesser recruitment of Zcf32 on the promoters of biofilm genes
in biofilm condition compared to the planktonic mode of growth. Taking together,
we propose that the transcription factor ZCF32 negatively regulates biofilm
development in C. albicans.
PMID- 27498701
TI - Fibroblast growth factor 21 deficiency exacerbates chronic alcohol-induced
hepatic steatosis and injury.
AB - Fibroblast growth factor 21 (FGF21) is a hepatokine that regulates glucose and
lipid metabolism in the liver. We sought to determine the role of FGF21 in
hepatic steatosis in mice exposed to chronic alcohol treatment and to discern
underlying mechanisms. Male FGF21 knockout (FGF21 KO) and control (WT) mice were
divided into groups that were fed either the Lieber DeCarli diet containing 5%
alcohol or an isocaloric (control) diet for 4 weeks. One group of WT mice exposed
to alcohol received recombinant human FGF21 (rhFGF21) in the last 5 days. Liver
steatosis and inflammation were assessed. Primary mouse hepatocytes and AML-12
cells were incubated with metformin or rhFGF21. Hepatic genes and the products
involved in in situ lipogenesis and fatty acid beta-oxidation were analyzed.
Alcohol exposure increased circulating levels and hepatic expression of FGF21.
FGF21 depletion exacerbated alcohol-induced hepatic steatosis and liver injury,
which was associated with increased activation of genes involved in lipogenesis
mediated by SREBP1c and decreased expression of genes involved in fatty acid beta
oxidation mediated by PGC1alpha. rhFGF21 administration reduced alcohol-induced
hepatic steatosis and inflammation in WT mice. These results reveal that alcohol
induced FGF21 expression is a hepatic adaptive response to lipid dysregulation.
Targeting FGF21 signaling could be a novel treatment approach for alcoholic
steatohepatitis.
PMID- 27498704
TI - The resveratrol analogue, 3,4,5,4'-trans-tetramethoxystilbene, inhibits the
growth of A375 melanoma cells through multiple anticancer modes of action.
AB - Resveratrol is a natural dietary product that has demonstrated multifaceted
anticancer activity. Several analogues of resveratrol have been synthesized in an
effort to enhance the pharmacological potency and improve the pharmacokinetic
properties of the compound. 3,4,5,4'-trans-tetramethoxystilbene (3,4,5,4'-TMS) is
a methoxylated analogue of resveratrol that has demonstrated anti-proliferative
activity in vitro (in cancer cell lines) and in vivo (in xenograft models). In
the present study, the anticancer effects of 3,4,5,4'-TMS in A375 human melanoma
cells were examined. 3,4,5,4'-TMS markedly inhibited the proliferation of A375
cells (IC50=0.7 uM), via a mechanism involving mitotic arrest at the prometaphase
stage of cell division. This effect was accompanied by the upregulation of the
expression of the mitogen activated protein kinases, JNK and p38, and the
concomitant activation of p38, that was verified by the nuclear translocation of
the phoshorylated form of the protein. The pharmacological inhibition of p38 by
SB203580 (4 uM) attenuated the effects of 3,4,5,4'-TMS, as demonstrated by
decreased cell cycle progression at the mitotic phase. Furthermore, 3,4,5,4'-TMS
increased the total levels of Aurora A, while it inhibited the localization of
the protein to the spindle poles. Finally, 3,4,5,4'-TMS exhibited anti-metastatic
activity, inhibiting A375 cell migration and the attachment of the cells to a
collagen type IV-coated surface. Collectively, the data suggest that 3,4,5,4'-TMS
is an effective chemotherapeutic drug for the treatment of human melanoma and
that it exerts its effects through multiple anticancer modes of action.
PMID- 27498703
TI - Dynamic Covalent Chemistry-based Sensing: Pyrenyl Derivatives of Phenylboronic
Acid for Saccharide and Formaldehyde.
AB - We synthesized two specially designed pyrenyl (Py) derivatives of phenylboronic
acid, PSNB1 and PSNB2, of which PSNB2 self-assemble to form dynamic aggregate in
methanol-water mixture (1:99, v/v) via intermolecular H-bonding and pi-pi
stacking. Interestingly, the dynamic aggregate shows smart response to presence
of fructose (F) as evidenced by fluorescence color change from green to blue.
More interestingly, the fluorescence emission of the resulted PSNB2-F changes
from blue to green with the addition of formaldehyde (FA). The reason behind is
formation of a PSNB2-F dimer via FA cross-linking. Based upon the reactions as
found, sensitive and fast sensing of F and FA in water was realized, of which the
experimental DLs could be significantly lower than 10 MUM for both analytes, and
the response times are less than 1 min. It is believed that not only the
materials as created may have the potential to find real-life applications but
also the strategy as developed can be adopted to develop other dynamic materials.
PMID- 27498702
TI - European Society of Cardiology Guideline-Adherent Antithrombotic Treatment and
Risk of Mortality in Asian Patients with Atrial Fibrillation.
AB - This study compared the risk of mortality in atrial fibrillation (AF) patients
treated adherent to the 2012 European Society of Cardiology (ESC) guidelines for
stroke prevention and those who were not treated according to guideline
recommendations. This study used the Taiwan National Health Insurance Research
Database. From 1996 to 2011, 354,649 newly diagnosed AF patients were identified
as the study population. Among the study cohort, 45,595 and 309,054 patients were
defined as Guideline-Adherent and Non-Adherent groups, respectively. During the
follow up of 1,480,280 person-years, 133,552 (37.7%) patients experienced
mortality. The risk of mortality was lower among AF patients whose treatment was
adherent to the guideline recommendation for stroke prevention than those whose
treatment was not (annual risk of mortality = 4.3% versus 10.0%) with an adjusted
hazard ratio of 0.62 (95% confidence interval = 0.61-0.64, p value < 0.001) after
adjusting for age, gender, CHA2DS2-VASc score and antiplatelet therapy. The
findings were consistently observed after propensity matching analysis. In
conclusion, the risk of mortality was lower for AF patients who were treated
according to the antithrombotic recommendations of the 2012 ESC guidelines,
guided by the CHA2DS2-VASc score. Better efforts to implement guidelines would
lead to improved outcomes for patients with AF.
PMID- 27498705
TI - Identification of brefelamide as a novel inhibitor of osteopontin that suppresses
invasion of A549 lung cancer cells.
AB - The contribution of aberrant osteopontin (OPN) expression to tumor progression
and metastasis has been documented in a wide spectrum of malignancies, and
targeted inhibition of OPN has therefore emerged as an attractive strategy for
cancer therapy. Transcription of OPN is regulated by various transcription
factors, and our recently published study demonstrated that downregulation of OPN
is an important event in the TGF-beta cytostatic program. We report here that
brefelamide exerts an inhibitory effect on OPN expression and function in A549
human lung carcinoma cells. The promoter, RNA, and protein levels of OPN were
decreased in brefelamide-treated A549 cells, which was accompanied by reduced
invasive ability in vitro. OPN inhibition by brefelamide was largely abrogated by
disruption of a putative TGF-beta inhibitory element in the OPN promoter.
Treatment with brefelamide induced Smad4 expression, and knockdown of Smad4 by
RNA interference partially diminished the inhibitory effect of brefelamide on
OPN. These results indicate that brefelamide inhibited OPN-mediated cell invasion
through restoration of the OPN repression by TGF-beta/Smad signaling. Together
with the reported antiproliferative property, our findings suggest that
brefelamide might serve as a potential candidate for the development of a new
antitumor and antimetastatic agent.
PMID- 27498706
TI - beta-Elemene enhances the efficacy of gefitinib on glioblastoma multiforme cells
through the inhibition of the EGFR signaling pathway.
AB - Glioblastoma multiforme (GBM) is the most common and severe form of primary tumor
in the central nervous system of adults which has poor prognosis and limited
therapeutic options. Epidermal growth factor receptor (EGFR) inhibitor, such as
gefitinib (brand name Iressa, ZD1839), has been approved as a targeted medicine
for several types of tumor including glioblastoma multiforme. However, gefitinib
exerted very limited effects on some glioblastoma multiforme patients after a
period of treatment due to intrinsic and acquired drug resistance. beta-Elemene,
a natural plant drug extracted from Curcuma wenyujin, has shown promising
anticancer effects against a broad spectrum of tumors. In the present study, we
found that beta-elemene could enhance the chemosensitivity of glioblastoma
multiforme cells to gefitinib. The combination medication of beta-elemene and
gefitinib not only inhibited the survival and proliferation of glioblastoma
multiforme cells via inhibition of EGFR signaling pathway but also induced more
distinct apoptosis and autophagy in the glioblastoma multiforme cells than the
gefitinib monotherapy. These results showed that beta-elemene might be one
potential adjuvant to enhance the effect of EGFR inhibitor and reduce the
resistance of gefitinib in glioblastoma multiforme.
PMID- 27498707
TI - Different infusion durations for preventing platinum-induced hearing loss in
children with cancer.
AB - BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin or
oxaliplatin, or a combination of these, is used to treat a variety of paediatric
malignancies. Unfortunately, one of the most important adverse effects is the
occurrence of hearing loss or ototoxicity. In an effort to prevent this
ototoxicity, different platinum infusion durations have been studied. This review
is an update of a previously published Cochrane review. OBJECTIVES: To assess the
effects of different durations of platinum infusion to prevent hearing loss or
tinnitus, or both, in children with cancer. Secondary objectives were to assess
possible effects of these infusion durations on: a) anti-tumour efficacy of
platinum-based therapy, b) adverse effects other than hearing loss or tinnitus,
and c) quality of life. SEARCH METHODS: We searched the electronic databases
Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library
2016, Issue 4), MEDLINE (PubMed) (1945 to 18 May 2016) and EMBASE (Ovid) (1980 to
18 May 2016). In addition, we handsearched reference lists of relevant articles
and we assessed the conference proceedings of the International Society for
Paediatric Oncology (2009 up to and including 2015) and the American Society of
Pediatric Hematology/Oncology (2014 and 2015). We scanned ClinicalTrials.gov and
the World Health Organization International Clinical Trials Registry Platform
(WHO ICTRP; apps.who.int/trialsearch) for ongoing trials (searched on 20 May 2016
and 24 May 2016 respectively). SELECTION CRITERIA: Randomised controlled trials
(RCTs) or controlled clinical trials (CCTs) comparing different platinum infusion
durations in children with cancer. Only the platinum infusion duration could
differ between the treatment groups. DATA COLLECTION AND ANALYSIS: Two review
authors independently performed the study selection, risk of bias assessment and
GRADE assessment of included studies, and data extraction including adverse
effects. Analyses were performed according to the guidelines of the Cochrane
Handbook for Systematic Reviews of Interventions. MAIN RESULTS: We identified one
RCT and no CCTs; in this update no additional studies were identified. The RCT
(total number of children = 91) evaluated the use of a continuous cisplatin
infusion (N = 43) versus a one-hour bolus cisplatin infusion (N = 48) in children
with neuroblastoma. For the continuous infusion, cisplatin was administered on
days 1 to 5 of the cycle but it is unclear if the infusion duration was a total
of 5 days. Methodological limitations were present. Only results from shortly
after induction therapy were provided. No clear evidence of a difference in
hearing loss (defined as asymptomatic and symptomatic disease combined) between
the different infusion durations was identified as results were imprecise (risk
ratio (RR) 1.39, 95% confidence interval (CI) 0.47 to 4.13, low quality
evidence). Although the numbers of children were not provided, it was stated that
tumour response was equivalent in both treatment arms. With regard to adverse
effects other than ototoxicity we were only able to assess toxic deaths. Again,
the confidence interval of the estimated effect was too wide to exclude
differences between the treatment groups (RR 1.12, 95% CI 0.07 to 17.31, low
quality evidence). No data were available for the other outcomes of interest
(i.e. tinnitus, overall survival, event-free survival and quality of life) or for
other (combinations of) infusion durations or other platinum analogues. AUTHORS'
CONCLUSIONS: Since only one eligible RCT evaluating the use of a continuous
cisplatin infusion versus a one-hour bolus cisplatin infusion was found, and that
had methodological limitations, no definitive conclusions can be made. It should
be noted that 'no evidence of effect', as identified in this review, is not the
same as 'evidence of no effect'. For other (combinations of) infusion durations
and other platinum analogues no eligible studies were identified. More high
quality research is needed.
PMID- 27498708
TI - Elevated IL-23R Expression and Foxp3+Rorgt+ Cells in Intestinal Mucosa During
Acute and Chronic Colitis.
AB - BACKGROUND IL-23/IL-23R signaling plays a pivotal role during the course of
inflammatory bowel diseases (IBD). However, the underlying mechanisms are poorly
characterized. Foxp3+ regulatory T cells are critical in the maintenance of gut
immune homeostasis and therefore are important in preventing the development of
IBD. This study was performed to clarify the association between IL-23/IL-23R
signaling and Foxp3+ regulatory T cells in colitis. MATERIAL AND METHODS Acute
and chronic mouse colitis models were established by administering mice DSS in
drinking water. IL-23R, IL-23, IL-I7, and IFN-gamma expression level, as well as
regulatory T cell, Th17-, and Th1-related transcription factors Foxp3, RORgt, and
T-bet were assayed by real-time PCR. The frequency of Foxp3+ RORgammat+ cells in
a Foxp3+ cell population in colon mucosa during acute and chronic colitis was
evaluated through flow cytometry. The signaling pathway mediated by IL-23R in the
colon mucosa from acute colitis mice and chronic colitis mice was monitored by
Western blot analysis. RESULTS We detected elevated IL-23R, IL-23, and IFN-gamma
expression in colon mucosa during acute and chronic colitis and found increased
IL-17 in acute colitis mice. Transcription factors Foxp3 and T-bet were elevated
in colon mucosa during acute and chronic colitis. Phosphorylation of Stat3 was
greatly enhanced, indicating the activation of IL-23R function in colitis mice.
The percentage of Foxp3+ T cells in acute and chronic colitis mice was comparable
to control mice, but there was a 2-fold increase of Foxp3+ RORgammat+ cells among
the Foxp3+ cell population in acute and chronic colitis mice compared to control
mice. CONCLUSIONS These findings indicate that the induction of Foxp3+ RORgt+ T
cells could be enhanced during inflammation in the intestine where IL-23R
expression is greatly induced. Our study highlights the importance of IL-23R
expression level and the instability of Foxp3+ regulatory T cells in the
development of inflammatory bowel diseases.
PMID- 27498710
TI - Local community playgroup participation and associations with social capital.
AB - Issue addressed The study aim was to investigate the relationships between social
capital measures and playgroup participation in a local residential area for
parents with children of playgroup age (1-4 years) compared with non
participation and participation in a playgroup outside the local residential
area. Research indicates playgroup participation has benefits for families,
however, less is known about the potential local community social capital for
parents who participate in playgroups. Methods Data were collected through a
cross-sectional survey from March 2013 to January 2014 in Perth, Western
Australia. The data from a group of parents (n=405) who had at least one child
aged between 1 and 4 years were analysed using multivariable regression. Reported
playgroup participation (local, outside the area or non-participation) in the
previous 12 months was investigated for associations with three measures
(Neighbourhood Cohesion Index, Social Capital and Citizenship Survey and local
reciprocity) that capture attributes of social capital. Results Participation in
playgroup locally was generally associated with higher levels of social capital
than both participation in playgroup outside the local area and non
participation. Mothers with two or more children fared better for social capital
measures than mothers with one child. Conclusions Participation in a locally
placed playgroup may provide an important opportunity for families with children
of playgroup age (1-4 years) to build social capital in their local community. So
what? Playgroups in a family's local area have the potential to foster locally
placed social capital through community interaction, social networks and
cohesion, which are important for mental health promotion in communities.
PMID- 27498709
TI - Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence
in human mesenchymal stem cells via Nrf2.
AB - Human mesenchymal stem cells (hMSCs) have great therapeutic potential due to
their high plasticity, immune privileged status and ease of preparation, as well
as a lack of ethical barriers to their use. However, their ultimate usefulness is
limited by cellular senescence occurring secondary to increased cellular levels
of reactive oxygen species (ROS) during their propagation in culture. The
underlying molecular mechanisms responsible for this process in hMSCs remain
unclear. An antioxidant polyphenol epigallocatechin-3-gallate (EGCG) found in
green tea, is known to activate nuclear factor-erythroid 2-related factor 2
(Nrf2), a master transcriptional regulator of antioxidant genes. Herein, we
examined the EGCG-mediated antioxidant mechanism in hMSCs exposed to ROS which
involves Nrf2 activation. The H2O2-exposed hMSCs showed cellular senescence with
significantly increased protein levels of acetyl-p53 and p21 in comparison with
the untreated hMSCs, and these effects were prevented by pre-treatment with EGCG.
By contrast, in Nrf2-knockdown hMSCs, EGCG lost its antioxidant effect,
exhibiting high levels of acetyl-p53 and p21 following EGCG pre-treatment and
H2O2 exposure. This indicates that Nrf2 and p53/p21 may be involved in the anti
senescent effect of EGCG in hMSCs. Taken together, these findings indicate the
important role of EGCG in preventing oxidative stress-induced cellular senescence
in hMSCs through Nrf2 activation, which has applications for the massive
production of more suitable hMSCs for cell-based therapy.
PMID- 27498711
TI - Proteomics applied to pediatric medicine: opportunities and challenges.
AB - INTRODUCTION: Care in pediatrics often refers to treatments directed to adults.
However, childhood is a specific life period, with molecular pathways connected
to development and thereby it requires distinctive considerations and special
treatments under disease. Proteomics can help to elucidate the molecular
mechanisms underlying the human development and disease onset in pediatric age
and this review is devoted to underline the results recently obtained in the
field. AREAS COVERED: The contribution of proteomics to the characterization of
physiological modifications occurring during human development is presented. The
proteomic studies carried out to elucidate the molecular mechanisms underlying
different pediatric pathologies and to discover new markers for early diagnosis
and prognosis of disease, comprising genetic and systemic pathologies, sepsis and
pediatric oncology are thereafter reported. The investigations concerning milk
composition in human and farm mammals are also presented. Finally, the chances
offered by the integration of different -omic platforms are discussed. Expert
commentary: The growing utilization of holistic technologies such as proteomics,
metabolomics and microbiomics will allow, in the near future, to define at the
molecular level the complexity of human development and related diseases, with
great benefit for future generations.
PMID- 27498712
TI - Efficacy of Local and Systemic Antimicrobials in the Non-Surgical Treatment of
Smokers With Chronic Periodontitis: A Systematic Review.
AB - BACKGROUND: The aim of this systematic review is to evaluate whether use of local
or systemic antimicrobials would improve clinical results of non-surgical
periodontal therapy for smokers with chronic periodontitis (CP). METHODS: Medical
Literature Analysis and Retrieval System Online, Excerpta Medica Database, and
The Cochrane Central Register of Controlled Trials were searched up to and
including March 2016. Randomized clinical trials of duration of at least 6 months
were included if they reported on treatment of smokers (>=10 cigarettes per day
for minimum 12 months) with CP with non-surgical periodontal therapy either alone
or associated with local or systemic antimicrobials. Random-effects meta-analyses
were undertaken to evaluate mean differences in probing depth (PD) and clinical
attachment level (CAL). RESULTS: Of 108 potentially eligible articles, seven were
included. Most individual studies (75%) testing locally delivered antibiotics
reported that smokers benefited from this treatment approach. Pooled estimates
found additional PD reduction of 0.81 mm (P = 0.01) and CAL gain of 0.91 mm (P =
0.01) at sites with baseline PD >=5 mm. Conversely, meta-analysis on systemic use
of antimicrobials failed to detect significant differences in mean changes from
baseline, and only one trial supported their use. CONCLUSIONS: In smokers with
CP, adjunctive use of local antimicrobials improved efficacy of non-surgical
periodontal therapy in reducing PD and improving CAL at sites presenting PD >=5
mm before treatment. Current evidence does not demonstrate similar gains when
scaling and root planing plus systemic antimicrobial/antibiotics were associated
with therapy.
PMID- 27498713
TI - A Novel Treatment Decision Tree and Literature Review of Retrograde Peri
Implantitis.
AB - BACKGROUND: Although retrograde peri-implantitis (RPI) is not a common sequela of
dental implant surgery, its prevalence has been reported in the literature to be
0.26%. Incidence of RPI is reported to increase to 7.8% when teeth adjacent to
the implant site have a previous history of root canal therapy, and it is
correlated with distance between implant and adjacent tooth and/or with time from
endodontic treatment of adjacent tooth to implant placement. Minimum 2 mm space
between implant and adjacent tooth is needed to decrease incidence of apical RPI,
with minimum 4 weeks between completion of endodontic treatment and actual
implant placement. The purpose of this study is to compile all available
treatment modalities and to provide a decision tree as a general guide for
clinicians to aid in diagnosis and treatment of RPI. METHODS: Literature search
was performed for articles published in English on the topic of RPI. Articles
selected were case reports with study populations ranging from 1 to 32 patients.
Any case report or clinical trial that attempted to treat or rescue an implant
diagnosed with RPI was included. RESULTS: Predominant diagnostic presentation of
a lesion was presence of sinus tract at buccal or facial abscess of apical
portion of implant, and subsequent periapical radiographs taken demonstrated a
radiolucent lesion. On the basis of case reports analyzed, RPI was diagnosed
between 1 week and 4 years after implant placement. Twelve of 20 studies reported
that RPI lesions were diagnosed within 6 months after implant placement. A step
by-step decision tree is provided to allow clinicians to triage and properly
manage cases of RPI on the basis of recommendations and successful treatments
provided in analyzed case reports. It is divided between symptomatic and
asymptomatic implants and adjacent teeth with vital and necrotic pulps.
CONCLUSIONS: Most common etiology of apical RPI is endodontic infection from
neighboring teeth, which was diagnosed within 6 months after implant placement.
Most common findings, radiographically and clinically, are lesions around implant
apex and sinus tract. A small number of implants did not improve with treatment.
Decision tree provides a path to diagnose and treat lesions to facilitate their
management. Further studies are needed to focus on histologic data around
periapical microbiota to establish specific etiology and differential diagnoses
compared with marginal peri-implantitis and other implant-related conditions.
PMID- 27498714
TI - An efficient and simple co-culture method for isolating primary human hepatic
cells: Potential application for tumor microenvironment research.
AB - Co-cultivation of non-parenchymal cells (NPCs) and tumor cells from the same
donor is important for metastatic cancer research. This study aimed to optimize a
protocol for liver NPC isolation. Two novel 3D organotypic co-culture models for
hepatocyte, endothelial cell (EC) and Kupffer cell (KC) isolation were used. Long
term cell co-culture, density gradient centrifugation and magnetic-activated cell
sorting (MACS) were established. ECs were isolated from the co-culture system;
the purity of the ECs was 92+/-1.2%. The island-like shape of hepatocytes was
noted in the 3D co-culture system, and spindle cells were found in the rest
space. Immunofluorescence analysis showed a net structure; the connective tissue
was positively stained with VE-cadherin or CD68, which were ECs and
KCs/macrophages. KCs were enriched in this system and separated by using
selective adherence to plastic. Clec4f+ KCs consisted of 87+/-6.3% of these
cells. Heterogeneous endothelium populations were detected, including sinusoid
ECs, microvascular ECs and hepatic lymphatic vessel epithelial cells. In
addition, hepatic progenitor cells were isolated and differentiated into
hepatoblasts. Dendritic cells (DCs), invariant natural killer T (iNKT) cells were
further separated by density gradient centrifugation and magnetic bead sorting.
In the present study, high protein expression levels of desmin and GFAP were
observed in the hepatic stellate cells (HSCs). Most of the HSCs were alpha-SMA
positive cells, which underlined the identity of activated HSCs. Intrahepatic
human biliary epithelial cells (hBECs) were semi-purified by centrifugation on a
Percoll gradient and were further immunopurified. In conclusion, we provide an
efficient long-term culture method to obtain liver NPCs in sufficient number and
purity.
PMID- 27498715
TI - Polyphenol-rich food general and on pregnancy effects: a review.
AB - This review aimed to investigate possible protective or deleterious effects of
polyphenol-rich foods (PRF) on chronic diseases, e.g. cardiovascular, and in
pregnant women, along with their antioxidant and anti-inflammatory action. A
great variety of foods and beverages, such as herbal teas, grape and orange
derivatives, dark chocolate, and many others contain high concentrations of
flavonoids and are freely consumed by the general population. In humans, PRF
consumption reduces lipid peroxidation, and several studies have shown a positive
correlation between an increased consumption of PRF and a decrease in the
incidence of cardiovascular disease. On the other hand, current studies have
suggested that maternal ingestion of PRF, especially during the third trimester
of pregnancy, could be associated to fetal ductal constriction (DC). Fetuses
exposed to this type of diet show higher ductal velocities and lower pulsatility
indexes, as well as larger right ventricles than those exposed to minimal amounts
of these substances. The underlying mechanism involved in these conditions has
not been entirely elucidated, but it seems to be a result of the antioxidant and
anti-inflammatory effects of polyphenols by some pathway. Furthermore, taking
into account the deleterious effect in late-pregnancy against the numerous
positive effects associated to polyphenols, this dual behavior deserves attention
particularly to control the dietary ingestion of PRF during gestation. In this
line, same PRF, natural constituents of human diet, may represent risk to fetal
in late pregnancy compared to the use of nonsteroidal anti-inflammatory drugs.
PMID- 27498716
TI - Acidic extracellular pH promotes prostate cancer bone metastasis by enhancing PC
3 stem cell characteristics, cell invasiveness and VEGF-induced vasculogenesis of
BM-EPCs.
AB - Bone metastasis is a main cause of cancer-related mortality in patients with
advanced prostate cancer. Emerging evidence suggests that the acidic
extracellular microenvironment plays significant roles in the growth and
metastasis of tumors. However, the effects of acidity on bone metastasis of PCa
remain undefined. In the present study, PC-3 cells were cultured in acidic medium
(AM; pH 6.5) or neutral medium (NM; pH 7.4), aiming to investigate the effects
and possible mechanisms of acidic extracellular microenvironment in bone
metastasis of PCa. Our results showed that AM can promote spheroid and colony
formations, cell viability and expression of stem cell characteristic-related
markers in PC-3 cells. Moreover, AM stimulates MMP-9 secretion and promotes
invasiveness of PC-3 cells, and these effects can be inhibited by blocking of MMP
9. Furthermore, AM stimulates VEGF secretion of PC-3 and AM conditioned medium
(CMAM) promotes vasculogenesis of BM-EPCs by increasing cell viability,
migration, tube formation, which involved activating the phosphorylation of VEGFR
2, Akt and P38, when pH of NM conditioned medium (CMNM) was modulated the same as
AM conditioned medium (CMAM). Further studies have shown that CMNM induced
vasculogenesis of BM-EPCs can be inhibited by the inhibition of VEGFR2 with DMH4.
These findings suggest that acidic extracellular microenvironment may have the
potential to modulate prostate cancer bone metastasis by enhancing PC-3 stem cell
characteristics, cell invasiveness and VEGF-induced vasculogenesis of BM-EPCs.
Improved anticancer strategies should be designed to selectively target acidic
tumor microenvironment.
PMID- 27498717
TI - Self gelating isoracemosol A, new racemosaceramide A, and racemosol E from
Barringtonia racemosa.
AB - Phytochemical investigation into the CHCl3 extract of the fruits of Barringtonia
racemosa resulted in the isolation of two new metabolites along with isoracemosol
A and betulinic acid as known metabolites. The new compounds were characterised
as phytosphingosine-type ceramide [(2S,3S,4R)-2-[(2R)-2-hydroxyhexadecanoyl
amino]-hexacos-8(E)-ene-1,3,4-triol, 1] and racemosol E [21beta-acetoxy-22alpha
(2-methylbutyroxy)-olean-12-ene-3beta,16alpha,28-triol, 2] on the basis of
extensive spectroscopic data analysis and chemical modifications. In addition,
the self-gelating property of isoracemosol A (3) was investigated for the first
time, which leads to the unexpected agglomerated porous-like morphology.
PMID- 27498718
TI - Prediction of a new ground state of superhard compound B6O at ambient conditions.
AB - Boron suboxide B6O, the hardest known oxide, has an Rm crystal structure (alpha
B6O) that can be described as an oxygen-stuffed structure of alpha-boron, or,
equivalently, as a cubic close packing of B12 icosahedra with two oxygen atoms
occupying all octahedral voids in it. Here we show a new ground state of this
compound at ambient conditions, Cmcm-B6O (beta-B6O), which in all quantum
mechanical treatments that we tested comes out to be slightly but consistently
more stable. Increasing pressure and temperature further stabilizes it with
respect to the known alpha-B6O structure. beta-B6O also has a slightly higher
hardness and may be synthesized using different experimental protocols. We
suggest that beta-B6O is present in mixture with alpha-B6O, and its presence
accounts for previously unexplained bands in the experimental Raman spectrum.
PMID- 27498719
TI - Preliminary investigation of numerical estimation of coagulated region generated
by interstitial microwave antenna.
AB - Microwave coagulation therapy (MCT) is an effective treatment for hepatocellular
carcinoma. During MCT, the target region is heated to induce coagulation in the
tissue, including cancer cells. Several types of antennas for MCT have been
developed, the heating performances of which were evaluated via specific
absorption rate (SAR) and temperature distribution. However, for coagulation
therapy, detailed evaluation of the coagulated region is important. Therefore, a
newly developed algorithm is presented for calculating the coagulated region
within biological tissue. To confirm the validity of the proposed method, the
calculated result is compared with the experimental findings.
PMID- 27498720
TI - Key toxicity issues with the WHO-recommended first-line antiretroviral therapy
regimen.
AB - INTRODUCTION: WHO recommends tenofovir, efavirenz, and lamivudine or
emtricitabine for first-line antiretroviral therapy (ART) in adults, which
replaced more toxic regimens using stavudine, zidovudine or nevirapine. Areas
covered: We searched Pubmed to identify observational studies and randomized
controlled trials reporting toxicity of these antiretrovirals published between
2011 and 2016, and hand-searched abstracts presented at major HIV conferences in
2015 and 2016, focusing on data from sub-Saharan Africa. Tenofovir's
nephrotoxicity manifests as mild renal tubular dysfunction (common and of
uncertain clinical significance), acute kidney injury (rare), and chronic
declining glomerular filtration rate (common). African studies, which include
high proportions of patients with renal dysfunction from opportunistic diseases,
report population improvement in renal function after starting tenofovir-based
ART. Tenofovir modestly decreases bone mineral density, and there is emerging
data that this increases fracture risk. Efavirenz commonly causes early self
limiting neuropsychiatric toxicity and hypersensitivity rashes. Recent studies
have highlighted its long-term neuropsychiatric effects, notably suicidality and
neurocognitive impairment, and metabolic toxicities (dyslipidemia, dysglycemia,
and lipoatrophy). We point out the challenges clinicians face in the recognition
and attribution of adverse drug reactions. Expert commentary: Tenofovir and
efavirenz are generally well tolerated, but both are associated with potentially
serious toxicities. Pharmacovigilance systems in resource-limited settings with
high HIV burden should be strengthened.
PMID- 27498721
TI - Facial eczema management protocols used on dairy farms in the North Island of New
Zealand and associated concentrations of zinc in serum.
AB - AIMS: To describe and evaluate the current practices used to manage and prevent
facial eczema (FE) in North Island dairy herds, and determine the within-herd
prevalence of cows with elevated activities of gamma glutamyl transferase (GGT),
and with concentrations of Zn in serum <18 MUmol/L. METHODS: Between January and
May 2014, 105 herd managers from throughout the North Island of New Zealand were
invited to participate in the study when regional spore counts for Pithomyces
chartarum started to rise towards 30,000 spores/g pasture. Managers selected 10
representative cattle that were weighed and blood-sampled by the herd
veterinarian. Blood samples were analysed for concentrations of Zn in serum and
GGT activity. Pasture samples were also collected and submitted for spore count
estimation. Finally a survey of farm management practices relating to prevention
of FE was completed by the herd manager. A mixed-effects logistic regression
model was used to determine associations between herd-level and cow-level
explanatory variables and the probability of a cow having a concentration of Zn
in serum <18 umol/L. RESULTS: Of the 1,071 cows tested, 79 (7.3 (95% CI=5.8
9.0)%) had GGT activity in serum >300 IU/L, and 35/106 (33 (95% CI=24.2-42.8)%)
herds had >=1 of the 10 cows sampled with GGT activity >300 IU/L. Of the 911 cows
that were being treated with Zn, concentrations of Zn were between 18-35 MUmol/L
in 398 (43.6 (95% CI=40.4-46.9)%) cows, were >35 MUmol/L in 32 (3.5 (95% CI=2.4
4.1)%) cows, and <18 MUmol/L in 479 (52.6 (95% CI=49.3-55.9)%) cows. After
adjusting for the confounding effect of region, the odds of a cow having
concentrations of Zn in serum <18 MUmol/L were 5.5 (95% CI=1.1-29) times greater
for cows supplemented with zinc in water compared with those supplemented by
drenching. Of the 105 herd managers, 103 (98%) stated that they had access to
regional spore count data, but only 35/105 (33%) reported that they measured
spore counts on their own farm. Overall, 98/105 (93%) managers reported that they
had some form of FE management programme in place. Fungicides were used on their
own or in combination with zinc treatments in 10 herds, ZnSO4 in water troughs
was used in 68 herds, oral drenching with ZnO in nine herds, and ZnO supplied in
feed in 26 herds. Estimated daily dose rates of zinc were less than that required
to treat a 400 kg cow on 42/68 farms that administered ZnSO4 in the water or ZnO
as a drench. CONCLUSION AND CLINICAL RELEVANCE: This study has shown that FE
management on dairy farms in the North Island of New Zealand could be
substantially improved. It is likely that improved FE management would occur if
herd managers were provided with more feedback on the success (or otherwise) of
their FE management programmes.
PMID- 27498723
TI - Cyclotetrahalo-p-phenylenes: simulations of halogen substituted
cycloparaphenylenes and their interaction with C60.
AB - Density functional calculations are used to study the role of edge
functionalization on the structure and electronic properties of
cycloparaphenylene (CPPs) containing from six to twenty benzenoid rings. We
substitute hydrogen by the halogens fluorine, chlorine and bromine. The resultant
Cyclotetrahalo-p-phenylenes are compared with their hydrogenated equivalents,
related linear paraphenyl and fluoro-paraphenyl polymers, and functionalised
armchair edges in graphene nanoribbons. Notably we consider both structural and
electronic evolution. Finally we examine C60@[10]CPP, i.e. C60 encapsulated
within [10]CPP, with the various ring terminations. The effect of halogenation on
electronic level position around the gap strongly affects their capacity to form
donor-acceptor pairs with fullerenes.
PMID- 27498722
TI - Physicochemical sequence characteristics that influence S-palmitoylation
propensity.
AB - Over the past 30 years, several hundred eukaryotic proteins spanning from yeast
to man have been shown to be S-palmitoylated. This post-translational
modification involves the reversible addition of a 16-carbon saturated fatty acyl
chain onto the cysteine residue of a protein where it regulates protein membrane
association and distribution, conformation, and stability. However, the large
scale proteome-wide discovery of new palmitoylated proteins has been hindered by
the difficulty of identifying a palmitoylation consensus sequence. Using a
bioinformatics approach, we show that the enrichment of hydrophobic and basic
residues, the cellular context of the protein, and the structural features of the
residues surrounding the palmitoylated cysteine all influence the likelihood of
palmitoylation. We developed a new palmitoylation predictor that incorporates
these identified features, and this predictor achieves a Matthews Correlation
Coefficient of .74 using 10-fold cross validation, and significantly outperforms
existing predictors on unbiased testing sets. This demonstrates that
palmitoylation sites can be predicted with accuracy by taking into account not
only physiochemical properties of the modified cysteine and its surrounding
residues, but also structural parameters and the subcellular localization of the
modified cysteine. This will allow for improved predictions of palmitoylated
residues in uncharacterized proteins. A web-based version of this predictor is
currently under development.
PMID- 27498725
TI - [Not Available].
PMID- 27498724
TI - Tour de France Champions born or made: where do we take the genetics of
performance?
AB - Cyclists in the Tour de France are endurance specialists. Twin and family studies
have shown that approximately 50% of the variance in a number of performance
related phenotypes (whether measured at baseline, i.e., natural talent, or in
response to training) including those important to cycling can be explained by
genetic variation. Research into the specific genetic variants that are
responsible has identified over 200 genes containing common genetic variants
involved in the genetic predisposition to physical performance. However,
typically these explain only a small portion of the variance, perhaps 1-2% and
collectively they rarely explain anything approaching the 50% of the variance
identified in the twin and family studies. Thus, there is a gap in our
understanding of the relationship between heritability and performance. This gap
may be bridged by investigation of rare variants or epigenetic variation or by
altering study designs through increased collaborations to pool existing cohorts
together. Initial findings from such efforts show promising results. This mini
review will touch on the genetics and epigenetics of sporting performance, how
they relate to cyclists in the Tour de France and where best future efforts may
be directed as well as discuss some preliminary research findings.
PMID- 27498726
TI - Second primary malignancies among patients with myeloma-related-diseases in the
KMF database.
AB - The incidence of second primary malignancies (SPMs) in Japanese patients with
myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum
(KMF) database registered from November 2012 to March 2015. We studied 1,571
cases. Hematologic malignancies were documented in 10 patients, and solid tumors
in 36 during this period. The cumulative 5-year incidence was estimated to be
1.0% for hematological malignancies and 3.7% for solid tumors. In the patients
with smoldering myeloma or MGUS without treatment, solid tumors but not
hematologic malignancies developed, though the cumulative incidence of each
malignancy did not differ significantly from that in patients receiving
treatment. Although statistical analysis showed that treatment with melphalan,
bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of
hematological malignancies, lenalidomide administration was more frequent in the
patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related
diseases more accurately, accumulation of a larger number of patients and longer
observation are needed.
PMID- 27498727
TI - The relation between clinical features of adult T-cell leukemia/lymphoma and the
serum levels of soluble CD25 and CD30.
AB - Adult T-cell leukemia (ATL) is an aggressive neoplasm of mature T cells. We aimed
to ascertain the relationships between soluble CD25 (sIL-2R) and CD30 (sCD30)
levels and nodal or extra-nodal involvement of ATL. Our study subjects were ATL
patients whose sIL-2R and sCD30 levels were measured before initial therapy
(n=32). Their sCD30 levels correlated significantly with the number of ATL cells
in peripheral blood (PB) (rho=0.456; P=0.009), while sIL-2R levels correlated
significantly with the number of nodal lesions (rho=0.660; P=0.001). We then also
assessed the relationships of pulmonary lesions with the number of ATL cells in
PB, lactate dehydrogenase levels, sIL-2R levels, and sCD30 levels in 24 patients
whose pleural effusions and hilar lymphadenopathy were investigated before
initial therapy. The results suggested that a high number of ATL cells in PB may
be associated with pulmonary lesions. It is known that metalloproteinases shed
and cleave cytokine receptors such as CD25 and CD30 from the cell surface as well
as E-cadherin and extracellular matrix. It seems that serum levels of sIL-2R and
sCD30 indicate the activation of metalloproteinases associated with ATL
involvement in vivo.
PMID- 27498728
TI - Rapid improvement of hyperammonemic encephalopathy by bortezomib treatment in IgD
type multiple myeloma.
AB - A 74-year-old man visited our hospital with complaints of anorexia, weight loss,
and impaired activities of daily living. He presented mild consciousness
disturbance at the first visit, but specific causes were identified. The IgD
level was>2,000 mg/dl and bone marrow biopsy was performed after aspiration
failed due to excessive density. He was diagnosed with IgD/lambda multiple
myeloma (MM). He lapsed into a coma with an extremely high ammonia level of 484
MUg/dl on day 8 after admission. His diagnosis was established as hyperammonemic
encephalopathy (HE). He was treated with dexamethasone (Dex) pulse therapy and
continuous hemodiafiltration. Minor improvement of hyperammonemia was achieved.
Combination therapy with bortezomib and Dex was commenced. His ammonia level
rapidly decreased and his mental state improved. HE accompanied by MM is rare and
further studies are needed to clarify outcomes in response to treatment using the
novel agent Bor. Although HE is potentially fatal, we found Bor to be rapidly
effective against HE.
PMID- 27498729
TI - Successful allogeneic bone marrow transplantation with reduced intensity
conditioning regimen for a pediatric relapsed ALK positive anaplastic large cell
lymphoma.
AB - Pediatric anaplastic large cell lymphoma (ALCL) is a chemosensitive malignancy,
but about 30% of patients experience relapse. In most of these patients, a second
complete remission is obtainable with salvage chemotherapy, though relapse free
survival rates are as low as 30-60%. Herein, we report a 6-year-old boy with
relapsed anaplastic lymphoma kinase (ALK) positive ALCL successfully treated with
vinblastine monotherapy followed by allogeneic hematopoietic stem cell
transplantation (allo-HSCT), with a reduced intensity conditioning (RIC) regimen,
from his father. One HLA locus from the father was mismatched. The boy had
neither severe graft-versus-host disease nor transplantation related
complications. He is currently well and has remained disease free for 10 months,
to date, since transplantation. Allo-HSCT with a RIC regimen may be a promising
treatment strategy for relapsed ALK positive ALCL based on obtaining graft-versus
lymphoma effects as well as reducing transplantation-related mortality.
PMID- 27498730
TI - Domestic dengue infection with hemophagocytic lymphohistiocytosis successfully
treated by early steroid therapy.
AB - A 34-year-old man, working at a park in Tokyo, Japan, was repeatedly bitten by
mosquitoes while cutting grass. He was hospitalized with sudden fever, fatigue,
and weakness. He was eventually diagnosed with dengue virus infection, detected
using reverse transcription polymerase chain reaction for the genome and by the
presence of nonstructural protein 1 in his peripheral blood. Symptomatic
treatments such as acetaminophen for the fever were not effective. Moreover,
peripheral blood examination showed drastically decreased white blood cells and
platelets, as well as marked elevations of ferritin and soluble interleukin 2
receptor. Furthermore, bone marrow examination revealed increased macrophages
with hemophagocytosis. Dengue infection with hemophagocytic lymphohistiocytosis
(HLH) was ultimately diagnosed. Half-dose steroid pulse therapy for three days
dramatically reduced his temperature, thereby ameliorating physical symptoms and
restoring normal peripheral blood data. He was discharged 12 days after
admission. Dengue infection with HLH is rare and this is the first report, to our
knowledge, of domestic dengue infection with HLH in Japan. Early steroid therapy
may be effective in such cases.
PMID- 27498731
TI - Successful rituximab treatment in an elderly patient with recurrent thrombotic
thrombocytopenic purpura.
AB - An 81-year-old man presenting with fever, neurological symptoms,
thrombocytopenia, and hemolytic anemia was diagnosed with acquired idiopathic
thrombotic thrombocytopenic purpura (TTP). His disintegrin-like and
metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity was
<1% and the ADAMTS13 inhibitor titer was 3.2 BU/ml. He received plasma exchange
and steroid administration until remission was achieved. Seven months later, he
suffered from paralysis of the right hand, hemolytic anemia, and
thrombocytopenia. We confirmed TTP recurrence based on ADAMTS13 activity <1% and
an ADAMTS13 inhibitor titer of 19.4 BU/ml. Four infusions of rituximab were
administered in addition to plasma exchange and steroid pulse therapy. Platelet
count recovery was observed within 5 days. No severe side effects related to
rituximab occurred. Although rituximab has not been approved for TTP in Japan, we
report the efficacy and safety of rituximab in an elderly patient with recurrent
TTP. We suggest that rituximab therapy should be started as soon as possible for
recurrent TTP in patients with high titers of ADAMTS13 inhibitor.
PMID- 27498732
TI - Musculoskeletal pain after stopping tyrosine kinase inhibitor in patients with
chronic myeloid leukemia: a questionnaire survey.
AB - We conducted a questionnaire survey to assess the state of patients with CML
after discontinuation of TKI therapy. Nine of 27 patients developed
musculoskeletal pain after TKI discontinuation. One had discontinued nilotinib
and eight had discontinued imatinib therapy. Median time to symptom development
after discontinuation was 2 weeks. Four experienced grade 3 symptoms as per the
CTCAE ver. 4.0. One had pain persisting over a period of 21 months. There was a
significant difference between patients with and without symptoms as regards
female gender and the probability of persistent MMR. Awareness of this withdrawal
syndrome after TKI discontinuation is imperative.
PMID- 27498733
TI - Primary immune thrombocytopenia accompanied by pituitary apoplexy.
AB - An 83-year-old woman was admitted to our hospital with a severe headache and
purpura. She had previously been diagnosed with idiopathic thrombocytopenia
purpura (ITP) and achieved complete remission with steroid therapy. Steroid
therapy had been completed one week prior to the current admission. The
recurrence of severe thrombocytopenia (<1.0*10(4) platelets/MUl) was detected and
a CT scan revealed pituitary hemorrhage without pituitary adenoma. She received
steroid therapy combined with intravenous immunoglobulin, which resulted in the
amelioration of ITP and improvements in the pituitary hemorrhage. Intracranial
hemorrhage, which is the most serious bleeding manifestation in ITP, is
relatively uncommon. Pituitary apoplexy in ITP is extremely rare.
PMID- 27498734
TI - Overview.
PMID- 27498735
TI - Recent advances in inherited bone marrow failure syndrome research.
AB - Inherited bone marrow failure syndromes (IBMFS) are a heterogeneous group of
genetic disorders characterized by bone marrow failure, congenital anomalies, and
an increased risk of malignancies. Diagnosis is often difficult due to the wide
variety of clinical expressions. The representative diseases are Diamond Blackfan
anemia (DBA), Fanconi anemia (FA), congenital sideroblastic anemia (CSA),
congenital dyserhthropoietic anemia, Shwachman Diamond syndrome, and dyskeratosis
congenita. Next-generation sequencing technologies have facilitated the discovery
of germline mutations that cause IBMFS. Recently, Japanese groups have identified
novel causative genes for DBA, FA and congenital thrombocytopenia by applying
whole exome-sequencing. In this review, we will highlight recent studies on DBA,
FA and CSA in Japan, which have employed next-generation sequencing technologies
to elucidate the genetic etiology of IBMFS.
PMID- 27498736
TI - Inherited genetic variants associated with childhood acute lymphoblastic leukemia
risk.
AB - Numerous efforts have been made to elucidate the roles of individual genetic
background factors in the risk of childhood acute lymphoblastic leukemia. Most
have taken the form of case-control studies focusing on specific candidate gene
polymorphisms. Recently, a more rigorous and comprehensive approach referred to
as a genome-wide association study (GWAS) has been widely utilized and has
achieved success. Case-control studies evaluating candidate gene associations
have shown cumulative evidence of a role for folate metabolism and xenobiotic
metabolism/transport pathway genetic variants. In addition, single nucleotide
polymorphism (SNP)s identified by GWAS appear to indicate a strong role for genes
encoding transcription factors involved in cellular differentiation. Further
studies are needed to clarify the accumulating evidence obtained from both
candidate gene and genome-wide investigations.
PMID- 27498737
TI - Familial acute lymphoblastic leukemia.
AB - Somatically acquired genomic alterations have been recognized as key hallmarks
inducing acute lymphoblastic leukemia (ALL), though recent knowledge acquired
from genome-wide association study (GWAS) has revealed that inherited genetic
variations (germline) are associated with ALL susceptibility as well as disease
onset. The proportion of ALL cases attributable to an inherited genetic
predisposition has been recognized as being much higher in clinical practice than
previously thought since familial cases with hematopoietic transcriptional
factors (PAX5 and ETV6) were reported. Considering the characteristics related to
inherited variants, issues associated with these variants persist from childhood
throughout the patient's entire life, and specific approaches to both familial
ALL cases and carriers with inherited variants are thus urgently needed. This
review focuses on familial ALL caused by the two aforementioned transcriptional
factors (PAX5 and ETV6).
PMID- 27498738
TI - Pharmacogenomics for leukemia treatment.
AB - The pharmacokinetics and pharmacodynamics of therapeutic drugs can greatly vary
among individuals. For example, it is sometimes necessary to alter the treatment
of childhood acute lymphoblastic leukemia from the standard protocol. Genetic
variation is one important factor, which can exert a wide range of effects on
sensitivities and responses to therapeutic agents. Thiopurine S-methyl
transferase (TPMT) is a useful test for predicting 6-mercaptopurine (6-MP)
sensitivity in Caucasians. However, it is not effective for predicting the 6-MP
therapeutic responses of Japanese patients because the frequency of TPMT
deficiency is lower in the Japanese population (approximately 1% versus
approximately 10% in Caucasians). Recently, NUDT15 polymorphisms have been
reported to be predictive factors contributing to responsiveness to thiopurine
therapy in Asians. The associations between genetic variants and therapeutic
responses have been reported in Western countries. However, questions remain
about whether results studying other races are applicable to Japanese due to
differences in genetic variant frequencies among races. To provide personalized
therapy based on genetic factors, we need to ascertain the relationships between
genetic variants and therapeutic responses in Japanese childhood acute
lymphoblastic leukemia cases.
PMID- 27498739
TI - Genetic abnormalities associated with the relapse of childhood leukemia.
AB - Acute leukemia, especially acute lymphoblastic leukemia, is the most common tumor
in childhood. Survival in pediatric acute leukemia cases has improved
significantly, but once a relapse occurs, the long-term survival rates decrease
markedly. Recently, SNP array and next-generation sequencing have revealed the
relapse mechanism of pediatric leukemia and genetic alterations which drive
leukemia recurrence.
PMID- 27498740
TI - A comparative perspective on erythropoiesis.
AB - The acquisition of fundamental information by the use of recent technologies,
including omics-based molecular analyses and total RNA sequencing, has opened the
door to further advances in physiological studies on new animal models.
Currently, we are endeavoring to develop a comparative hematology protocol in
order to build a discovery platform. All vertebrates, with the exception of a few
species, have universally peripheral erythrocytes and hemoglobin, suggesting
erythropoiesis to be an evolutionary index.
PMID- 27498741
TI - Phylogenic insights into the enucleation of erythroblasts in human.
AB - Two key questions remain unanswered in the erythropoiesis field: Why and how do
erythroblasts enucleate in mammalian species? Recent studies have unveiled the
roles of various molecules, cytoskeletal proteins, motor proteins, vesicle
transport, signaling pathways, lipid rafts and actomyosin ring contraction in the
enucleation process. However, few reports provide insights into the fitness
benefit for mammalian species of having anucleate erythrocytes. Herein, we
discuss the biological significance of enucleation of human erythroblasts based
on our recent results and on evolutionary considerations related to the biology
of hemoglobin and the comparative biochemistry of erythrocyte membrane
cytoskeletal proteins, such as protein 4.1R. We specifically focus on the
Mesozoic era, a geological period during which dinosaurs and the ancestors of
mammalian species coexisted. Approximately 200 million years ago, at the
beginning of this era, the earth's atmosphere was hypoxic. Interestingly, animals
adopted different respiration systems to adapt to this hypoxic environment.
Recent studies using state-of-the-art technologies have shown that dinosaurs
might have had nucleated erythrocytes. After dinosaurs became extinct about 65.5
million years ago, their respiration system was maintained by birds. We propose a
new adaptive theory that establishes a correlation between evolution towards
nucleated or anucleate erythrocytes depending on organism respiration systems
during the Mesozoic era.
PMID- 27498742
TI - Embryonic regulation of the mouse erythropoietic niche and its clinical
application.
AB - Erythropoiesis has classically been described as occurring in two waves: first
primitive and then definitive erythropoiesis. In the mouse embryo, definitive
erythropoiesis begins in the yolk sac and then shifts to the liver, spleen, and
bone marrow. The fetal liver serves as the primary organ for erythroid cell
expansion and maturation at mid-gestation and its mechanisms have been well
investigated with special attention to niche cells expressing cytokines such as
SCF, TPO and IGF2. Previously, our group reported that DLK1(+) hepatoblasts
support fetal liver hematopoiesis, particularly erythropoiesis, through EPO, SCF
and matrix secretion. Loss of DLK1(+) hepatoblasts in Map2k4(-/-) mouse embryos
resulted in decreased numbers of hematopoietic cells in the fetal liver. When
sorted DLK1(+) hepatoblasts were further analyzed by microarray, several genes
encoding proteinases and peptidases were highly expressed in DLK1(+)
hepatoblasts. Based on the hypothesis that high molecular weight proteins are
digested into small peptides that may regulate hematopoiesis, we screened out
peptides, and identified KS-13 (PCT/JP2010/067011). Both KS-13 and modified KS
13, known as SL-13R, proliferate and increase the number of hematopoietic
stem/progenitors from human cord blood cells in vitro. We hereby present our
findings on the extrinsic regulation of embryonic erythropoiesis with special
attention to niche cells, identification of niche-derived peptides, and
implications for future hematotherapy.
PMID- 27498743
TI - Roles of transferrin receptors in erythropoiesis.
AB - Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is
mainly provided by macrophages and the intestines in a transferrin (Tf)-bound
form. Bone marrow erythroblasts incorporate Tf through endocytosis, which is
mediated by transferrin receptor 1 (TFR1). Recently, human TFR1, aside from its
role as a Tf receptor, was also found to be a receptor for the H-subunit of
ferritin (FTH). In humans, hematopoietic erythroid precursor cells express high
levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin). H
ferritin inhibits the formation of burst forming unit-erythroid colonies in
vitro. TFR2, which is also a Tf receptor, is predominantly expressed in
hepatocytes and erythroid precursor cells. In the liver, TFR2 forms a complex
with HFE, a hereditary hemochromatosis-associated protein, and acts as an iron
sensor. In mice, hepatocyte-specific knockout of the TFR2 gene has been shown to
cause systemic iron-overload with decreased expression of hepcidin, the central
regulator of iron homeostasis. In erythroid cells, TFR2 forms a complex with the
erythropoietin receptor and facilitates its trafficking to the cell membrane.
Moreover, hematopoietic cell-specific knockout of the TFR2 gene causes microcytic
erythrocytosis in mice. This review focuses on the molecular evolution and
functions of these TFRs and their ligands.
PMID- 27498744
TI - [Not Available].
PMID- 27498746
TI - Potential Universal Application of High-intensity Interval Training from Athletes
and Sports Lovers to Patients.
AB - Recently, high-intensity interval training (HIIT) has received much attention as
a promising exercise option not only to improve aerobic fitness, but also to
prevent and improve lifestyle-related diseases. Epidemiological studies have
shown that the exercise volume, as determined by the product of exercise
intensity, duration, and frequency, has been shown to be important for
improvements in muscle mitochondrial activity and subsequent improvements in
aerobic fitness, insulin sensitivity, and metabolic variables. Therefore,
continuous moderate-intensity training has been widely recommended. On the other
hand, the main contributor of HIIT to improvements in aerobic fitness and
metabolic variables is its high-intensity nature, and many recent studies have
shown results favoring HIIT when compared with conventional continuous training,
despite its shorter exercise duration and smaller exercise volume. In this
review, we aim to show the possible universal application of HIIT in a hospital
setting, where athletes, sports lovers, and patients have sought medical advice
and have the opportunity to undergo detailed evaluations, including an exercise
stress test. For athletes, HIIT is mandatory to achieve further improvements in
aerobic fitness. For patients, though higher levels of motivation and careful
evaluation are required, the time constraints of HIIT are smaller and both
aerobic and resistance training can be expected to yield favorable results
because of the high-intensity nature of HIIT.
PMID- 27498747
TI - Dose response of dexmedetomidine-induced resistance to hypoxia in mice.
AB - Tolerance to hypoxia can be induced by reducing oxygen consumption.
Dexmedetomidine (DEX) decreases locomotor activity and induces bradycardia and
hypothermia in mice. The present study examined the hypothesis that DEX improves
hypoxia tolerance in mice. Adult mice received an intraperitoneal injection of 1,
5, 10, 20, 40, 80, 160 or 320 ug/kg DEX, 20 mg/kg propranolol or saline. Acute
hypoxic conditions were induced by placing the mice in a limited enclosed
container with soda lime. Core body temperature (CBT) and heart rate (HR) were
measured prior to and 30 min after drug administration. Survival time was
monitored in the sealed container. Survival times (mean +/- standard deviation)
of mice in the saline, 1, 5, 10, 20, 40, 80, 160 and 320 ug/kg DEX, and the 20
mg/kg propranolol groups were 22.4+/-1.1, 23.4+/-1.1, 26.0+/-0.9, 36.9+/-5.2,
42.4+/-2.9, 43.2+/-2.3, 58.2+/-4.2, 80.5+/-4.0, 79.2+/-6.0, and 38.2+/-2.8 min,
respectively. Pretreatment with propranolol and 10, 20, 40, 80, 160 or 320 ug/kg
DEX, but not 1 or 5 ug/kg, significantly prolonged survival time compared with
saline-injected mice (P<0.05 or P<0.01). CBT and HR decreased in a similar
manner. The correlation coefficients between survival time and CBT, and survival
time and HR were -0.802 and -0.726, respectively. Thus, DEX dose-dependently
enhances hypoxia tolerance in mice. In conclusion, it is suggested that DEX may
be used in clinical practice as a novel protective agent for organs and tissues
during hypoxic injury.
PMID- 27498748
TI - The diagnostic value of three sacroiliac joint pain provocation tests for
sacroiliitis identified by magnetic resonance imaging.
AB - OBJECTIVES: The aim of the current study was to investigate the diagnostic value
of three sacroiliac (SI) joint pain provocation tests for sacroiliitis identified
by magnetic resonance imaging (MRI) and stratified by gender. METHOD: Patients
without clinical signs of nerve root compression were selected from a cohort of
patients with persistent low back pain referred to an outpatient spine clinic.
Data from Gaenslen's test, the thigh thrust test, and the long dorsal sacroilia
ligament test and sacroiliitis identified by MRI were analysed. RESULTS: The
median age of the 454 included patients was 33 (range 18-40) years and 241 (53%)
were women. The prevalence of SI joints with sacroiliitis was 5%. In the whole
study group, only the thigh trust test was associated with sacroiliitis, the area
under the receiver operating characteristic (ROC) curve (AUC) was 0.58 [95%
confidence interval (CI) 0.51-0.65], sensitivity 31% (95% CI 18-47), and
specificity 85% (95% CI 82-87). In men, sacroiliitis was associated with all the
SI joint tests assessed and multi-test regimens, with the greatest AUC found for
at least one positive out of three tests [AUC 0.68 (95% CI 0.56-0.80),
sensitivity 56% (95% CI 31-79), and specificity 81% (95% CI 77-85)]. In women, no
significant associations were observed between the SI joint tests and
sacroiliitis. CONCLUSIONS: Only in men were the SI joint tests found to be
associated with sacroiliitis identified by MRI. Although, the diagnostic value
was relatively low, the results indicate that the use of SI joint tests for
sacroiliitis may be optimized by gender-separate analyses.
PMID- 27498749
TI - Tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone, exhibits potent antiangiogenic
activity in vitro.
AB - Tumor growth and metastasis depend on angiogenesis triggered by chemical signals,
such as vascular endothelial growth factor (VEGF), released from tumor cells.
Therefore, the specific perturbation of angiogenesis has been considered a
powerful strategy for the treatment of cancer. Herein, we report that tricin,
4',5,7-trihydroxy-3',5'-dimethoxyflavone, exhibits potent antiangiogenic activity
in vitro. Tricin effectively suppressed the proliferation as well as VEGF-induced
invasion and tube formation of human umbilical vein endothelial cells (HUVECs) at
subtoxic doses. Furthermore, tricin significantly inhibited the angiogenesis of
the chorioallantoic membrane from growing chick embryos without showing
cytotoxicity. We also found that tricin blocked tumor cell-induced angiogenesis.
Notably, tricin downregulated not only the VEGFR2 signal transduction by reducing
reactive oxygen species (ROS) generation in endothelial cells, but also the
expression of VEGF by inhibiting hypoxia inducible factor-1alpha (HIF-1alpha)
accumulation in tumor cells. Moreover, combined treatment with tricin and
bevacizumab, an anti-VEGF drug, ameliorated the antiangiogenic effect of
bevacizumab. Taken together, our findings demonstrate for the first time that
tricin possesses promising antiangiogenic potential and thus may be applied to
anticancer therapy by targeting tumor angiogenesis.
PMID- 27498750
TI - Gas phase ultraviolet and infrared spectroscopy on a partial peptide of beta2
adrenoceptor SIVSF-NH2 by a laser desorption supersonic jet technique.
AB - Laser desorption supersonic jet laser spectroscopy has been applied to a penta
peptide, Ser-Ile-Val-Ser-Phe-NH2 (SIVSF-NH2), which is a partial sequence of a
binding site in a beta2-adrenaline receptor protein. By comparing the resonance
enhanced multiphoton ionization spectrum with the ultraviolet-ultraviolet hole
burning (HB) spectrum, it is concluded that only a single conformer exists. The
infrared (IR) spectrum of the X-H stretching region, measured by IR dip
spectroscopy, shows that all of the OH and NH groups form hydrogen bonds. The
structure of SIVSF-NH2 is assigned by the combination of a force field
calculation (CONFLEX) and quantum chemical calculations both in S0 and S1. Over
20 000 stable conformations, given by CONFLEX, are classified into 6987 groups
and 1068 groups in which all of the NH and OH bonds are hydrogen-bonded are
selected. The most stable structure in each group was geometrically optimized by
density functional theory (DFT) calculations, and theoretical IR spectra were
calculated for the conformers for which the energies are within 10 kJ mol(-1) of
the most stable one. It has been found that the most stable and the secondmost
stable conformers well-reproduce the observed IR spectrum. The vibrational
frequencies in S1 were also calculated for these two conformers. According to the
reproduction of the vibrational frequencies in the HB spectrum, the structure of
SIVSF-NH2 is assigned to the most stable conformer, which forms a hydrogen-bonded
structure corresponding to a compact, distorted version of the beta hairpin of
peptides and proteins.
PMID- 27498751
TI - Erratum: MicroRNAs in Breast Cancer: One More Turn in Regulation.
AB - In the article entitled, "MicroRNAs in Breast Cancer: One More Turn in
Regulation" published in Current Drug Targets 2016 Volume 17, No. 9, pg no. 1083,
the authors' names need to be replaced with the following as provided by the
corresponding author. MicroRNAs in Breast Cancer: One More Turn in Regulation.
Pilar Eroles, Eduardo Tormo, Begona Pineda, Estefania Espin and Ana Lluch.
PMID- 27498752
TI - Effect of sudden addition of PCE and bioreactor coupling to ZVI filters on
performance of fluidized bed bioreactors operated in simultaneous electron
acceptor modes.
AB - The present work evaluated the effects of (i) feeding a water contaminated with
80 mg/L PCE to bioreactors seeded with inoculum not acclimated to PCE, (ii)
coupling ZVI side filters to bioreactors, and (iii) working in different
biological regimes, i.e., simultaneous methanogenic aeration and simultaneous
methanogenic-denitrifying regimes, on fluidized bed bioreactor performance.
Simultaneous electron acceptors refer to the simultaneous presence of two
compounds operating as final electron acceptors in the biological respiratory
chain (e.g., use of either O2 or NO3- in combination with a methanogenic
environment) in a bioreactor or environmental niche. Four lab-scale, mesophilic,
fluidized bed bioreactors (bioreactors) were implemented. Two bioreactors were
operated as simultaneous methanogenic-denitrifying (MD) units, whereas the other
two were operated in partially aerated methanogenic (PAM) mode. In the first
period, all bioreactors received a wastewater with 1 g chemical oxygen demand of
methanol per liter (COD-methanol/L). In a second period, all the bioreactors
received the wastewater plus 80 mg perchloroethylene (PCE)/L; at the start of
period 2, one MD and one PAM were coupled to side sand-zero valent iron filters
(ZVI). All bioreactors were inoculated with a microbial consortium not acclimated
to PCE. In this work, the performance of the full period 1 and the first 60 days
of period 2 is reported and discussed. The COD removal efficiency and the nitrate
removal efficiency of the bioreactors essentially did not change between period 1
and period 2, i.e., upon PCE addition. On the contrary, specific methanogenic
activity in PAM bioreactors (both with and without coupled ZVI filter)
significantly decreased. This was consistent with a sharp fall of methane
productivity in those bioreactors in period 2. During period 2, PCE removals in
the range 86 to 97 % were generally observed; the highest removal corresponded to
PAM bioreactors along with the highest dehalogenation efficiency (94 %).
Principal component analysis as well as cluster analysis confirmed the trends
mentioned above, i.e., the better performance of PAM over MD, and the unexpected
no effect of the ZVI side filters on PCE removal and dehalogenation efficiencies.
To the best of our knowledge, this is the first report on the combined treatment
ZVI-biological of a water polluted with PCE, where the biological operation
relied on simultaneous electron acceptors.
PMID- 27498753
TI - Tailoring the properties of acetate-based ionic liquids using the
tricyanomethanide anion.
AB - The equilibrium and transport properties of mixtures of two ionic liquids -
[C4C1Im][OAc] and [C4C1Im][C(CN)3] - were determined and interpreted at the
molecular level using vibration spectroscopy, NMR and molecular dynamics
simulation. The non-ideality of the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x was
characterized by V(E) = +0.28 cm(3) mol(-1) (293 K, x = 0.65) and H(E) = -2.2 kJ
mol(-1) for x = 0.5. These values could be explained by a rearrangement of the
hydrogen-bond network of the mixture that favours the interaction of the acetate
anion with the imidazolium cation at position C2. The dynamic properties of the
mixture are also dramatically influenced by the composition with a decrease of
the viscosity and an increase of self-diffusion coefficients of the ions when the
amount of tricyanomethanide anion increases in the mixture.
PMID- 27498754
TI - Ringiculid bubble snails recovered as the sister group to sea slugs (Nudipleura).
AB - Euthyneuran gastropods represent one of the most diverse lineages in Mollusca
(with over 30,000 species), play significant ecological roles in aquatic and
terrestrial environments and affect many aspects of human life. However, our
understanding of their evolutionary relationships remains incomplete due to
missing data for key phylogenetic lineages. The present study integrates such a
neglected, ancient snail family Ringiculidae into a molecular systematics of
Euthyneura for the first time, and is supplemented by the first microanatomical
data. Surprisingly, both molecular and morphological features present compelling
evidence for the common ancestry of ringiculid snails with the highly dissimilar
Nudipleura-the most species-rich and well-known taxon of sea slugs (nudibranchs
and pleurobranchoids). A new taxon name Ringipleura is proposed here for these
long-lost sisters, as one of three major euthyneuran clades with late Palaeozoic
origins, along with Acteonacea (Acteonoidea + Rissoelloidea) and Tectipleura
(Euopisthobranchia + Panpulmonata). The early Euthyneura are suggested to be at
least temporary burrowers with a characteristic 'bubble' shell, hypertrophied
foot and headshield as exemplified by many extant subtaxa with an infaunal mode
of life, while the expansion of the mantle might have triggered the explosive
Mesozoic radiation of the clade into diverse ecological niches.
PMID- 27498756
TI - Anion Redox Chemistry in the Cobalt Free 3d Transition Metal Oxide Intercalation
Electrode Li[Li0.2Ni0.2Mn0.6]O2.
AB - Conventional intercalation cathodes for lithium batteries store charge in redox
reactions associated with the transition metal cations, e.g., Mn(3+/4+) in
LiMn2O4, and this limits the energy storage of Li-ion batteries. Compounds such
as Li[Li0.2Ni0.2Mn0.6]O2 exhibit a capacity to store charge in excess of the
transition metal redox reactions. The additional capacity occurs at and above 4.5
V versus Li(+)/Li. The capacity at 4.5 V is dominated by oxidation of the O(2-)
anions accounting for ~0.43 e(-)/formula unit, with an additional 0.06 e(
)/formula unit being associated with O loss from the lattice. In contrast, the
capacity above 4.5 V is mainly O loss, ~0.08 e(-)/formula. The O redox reaction
involves the formation of localized hole states on O during charge, which are
located on O coordinated by (Mn(4+)/Li(+)). The results have been obtained by
combining operando electrochemical mass spec on (18)O labeled
Li[Li0.2Ni0.2Mn0.6]O2 with XANES, soft X-ray spectroscopy, resonant inelastic X
ray spectroscopy, and Raman spectroscopy. Finally the general features of O redox
are described with discussion about the role of comparatively ionic (less
covalent) 3d metal-oxygen interaction on anion redox in lithium rich cathode
materials.
PMID- 27498755
TI - Hydrogen prevents corneal endothelial damage in phacoemulsification cataract
surgery.
AB - In phacoemulsification, ultrasound induces hydroxyl radical (.OH) formation,
damaging corneal endothelium. Whether H2 can prevent such oxidative damage in
phacoemulsification was examined by in vitro and in vivo studies. H2 was
dissolved in a commercial irrigating solution. The effects of H2 against .OH
generation were first confirmed in vitro by electron-spin resonance (ESR) and
hydroxyphenyl fluorescein (HPF). ESR showed a significantly decreased signal
magnitude, and fluorescence intensity by oxidized HPF was significantly less in
the H2-dissolved solution. The effects of H2 in phacoemulsification were
evaluated in rabbits, comparing H2-dissolved and control solutions. Five hours
after the procedure, the whole cornea was excised and subjected to image analysis
for corneal edema, real-time semiquantitative PCR (qPCR) for heme oxygenase (HO)
1, catalase (CAT), superoxide dismutase 1 (SOD1), and SOD2 mRNA, and
immunohistochemistry. Corneal edema was significantly less and the increases in
anti-oxidative HO-1, CAT and SOD2 mRNA expressions were significantly suppressed
in the H2 group. In addition, corneal endothelial cell expressions of two
oxidative stress markers, 4-HNE and 8-OHdG, were significantly lower in the H2
group. In conclusion, H2 dissolved in the ocular irrigating solution protected
corneal endothelial cells from phacoemulsification-induced oxidative stress and
damage.
PMID- 27498757
TI - Post-bronchiolitis wheezing is associated with toll-like receptor 9 rs187084 gene
polymorphism.
AB - Innate immunity receptors play a critical role in host defence, as well as in
allergy and asthma. The aim of this exploratory study was to evaluate whether
there are associations between TLR7 rs179008, TLR8 rs2407992, TLR9 rs187084 or
TLR10 rs4129009 polymorphisms and viral findings, clinical characteristics or
subsequent wheezing in infants with bronchiolitis. In all, 135 full-term infants
were hospitalized for bronchiolitis at age less than 6 months: 129 of them were
followed-up until the age of 1.5 years. The outcome measures were repeated
wheezing, use of inhaled corticosteroids, atopic dermatitis during the first 1.5
years of life and total serum immunoglobulin E (IgE). There were no significant
associations between the genotypes or allele frequencies of TLR7 rs179008, TLR8
rs2407992, TLR9 rs187084 or TLR10 rs4129009 polymorphisms and clinical
characteristics or the severity of bronchiolitis during hospitalization. During
follow-up, repeated wheezing was more common in children with TLR9 rs187084
variant genotype CC (30.5%) than in children with TLR9 wild-type genotype TT
(12.2%) (p = 0.02, aOR 2.73, 95% CI 1.02-7.29). The TLR10 rs4129009 minor allele
G was associated with elevated total serum IgE. TLR9 rs187084 gene polymorphism
may be associated with post-bronchiolitis wheezing, and TLR10 rs4129009 gene
polymorphism may be associated with atopy.
PMID- 27498758
TI - Development, Implementation, and Evaluation of an Interdisciplinary Women's
Health and Laboratory Course.
AB - OBJECTIVES: To describe the creation, implementation, and evaluation of a case
based, interdisciplinary course that highlights laboratory principles for
students who have selected a career in obstetrics and gynecology. METHODS: We
developed four case-based modules with questions that emphasize laboratory
principles required to establish a diagnosis and treat and monitor each case
based scenario. The cases were offered as a 4-hour elective course during the
medical school capstone. A clinician and a clinical pathologist pair facilitated
the case discussions with groups of six to nine medical students during 2
consecutive years. Pre- and postknowledge quizzes were given to the students. In
addition, a structured evaluation of the course was performed. RESULTS: Twenty
two students participated in the courses. Most found the format effective and the
information useful. There was a significant increase in their related knowledge
as established by pre- and posttesting. CONCLUSIONS: Case-based discussions gave
learners a better understanding of the function and complexity of the clinical
laboratories, and multidisciplinary facilitation highlighted the value of
interacting with laboratory professionals to enhance clinical care.
PMID- 27498759
TI - Distribution of Silver Nanoparticles to Breast Milk and Their Biological Effects
on Breast-Fed Offspring Mice.
AB - Recent rodent studies have shown that nanoparticles are distributed to breast
milk, and more-detailed safety information regarding nanoparticle consumption by
lactating mothers is required. Here, we used mice to investigate the safety of
nanoparticle use during lactation. When Ag and Au nanoparticles were
intravenously administered to lactating mice, the nanoparticles were distributed
to breast milk without producing apparent damage to the mammary gland, and the
amount of Ag nanoparticles distributed to breast milk increased with decreasing
particle size. Orally administered Ag nanoparticles were also distributed to
breast milk and subsequently to the brains of breast-fed pups. Ten-nanometer Ag
nanoparticles were retained longer in the pups' brains than in their livers and
lungs. Nevertheless, no significant behavioral changes were observed in offspring
breast-fed by dams that had received orally administered 10 nm Ag nanoparticles.
These data provide basic information for evaluating the safety of nanoparticle
use during lactation.
PMID- 27498760
TI - Synthesis of Zwitterionic Polymer Particles via Combined Distillation
Precipitation Polymerization and Click Chemistry for Highly Efficient Enrichment
of Glycopeptide.
AB - Because of the low abundance of glycopeptide in natural biological samples,
methods for efficient and selective enrichment of glycopeptides play a
significant role in mass spectrometry (MS)-based glycoproteomics. In this study,
a novel kind of zwitterionic hydrophilic interaction chromatography polymer
particles, namely, poly(N,N-methylenebisacrylamide-co-methacrylic acid)@l-Cys
(poly(MBAAm-co-MAA)@l-Cys), for the enrichment of glycopeptides was synthesized
by a facile and efficient approach that combined distillation precipitation
polymerization (DPP) and "thiol-ene" click reaction. In the DPP approach,
residual vinyl groups explored outside the core with high density, then the
functional ligand cysteine was immobilized onto the surface of core particles by
highly efficient thiol-ene click reaction. Taking advantage of the unique
structure of poly(MBAAm-co-MAA)@l-Cys, the resulting particles possess remarkable
enrichment selectivity for glycopeptides from the tryptic digested human
immunoglobulin G. The polymer particles were successfully employed for the
analysis of human plasma, and 208 unique glycopeptides corresponding to 121
glycoproteins were reliably identified in triple independent nano-LC-MS/MS runs.
The selectivity toward glycopeptides of these particles poly(MBAAm-co-MAA)@l-Cys
is ~2 times than that of the commercial beads. These results demonstrated that
these particles had great potential for large-scale glycoproteomics research.
Moreover, the strategy with the combination of DPP and thiol-ene click chemistry
might be a facile method to produce functional polymer particles for
bioenrichment application.
PMID- 27498761
TI - Crystal structure of the plant receptor-like kinase TDR in complex with the TDIF
peptide.
AB - In plants, leucine-rich repeat receptor-like kinases (LRR-RKs) perceive ligands,
including peptides and small molecules, to regulate various physiological
processes. TDIF, a member of the CLE peptide family, specifically interacts with
the LRR-RK TDR to inhibit meristem differentiation into tracheary elements, and
promotes cell proliferation. Here we report the crystal structure of the
extracellular domain of TDR in complex with the TDIF peptide. The extracellular
domain of TDR adopts a superhelical structure comprising 22 LRRs, and
specifically recognizes TDIF by its inner concave surface. Together with our
biochemical and sequence analyses, our structure reveals a conserved TDIF
recognition mechanism of TDR among plant species. Furthermore, a structural
comparison of TDR with other plant LRR-RKs suggested the activation mechanism of
TDR by TDIF. The structure of this CLE peptide receptor provides insights into
the recognition mechanism of the CLE family peptides.
PMID- 27498763
TI - The diastereoselective synthesis of octahedral cationic iridium hydride complexes
with a stereogenic metal centre.
AB - We report herein the highly diastereoselective synthesis of octahedral cationic
Ir(iii) hydride complexes with a stereogenic metal centre following various
strategies. The configurational stability of these compounds has also been
investigated.
PMID- 27498762
TI - A VEGF-dependent gene signature enriched in mesenchymal ovarian cancer predicts
patient prognosis.
AB - We have previously reported surrogate biomarkers of VEGF pathway activities with
the potential to provide predictive information for anti-VEGF therapies. The aim
of this study was to systematically evaluate a new VEGF-dependent gene signature
(VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis.
Using microarray profiling and cross-species analysis, we identified 140-gene
mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of
vasculature and basement membrane genes. In patients who received bevacizumab
therapy and showed partial response, the expressions of VDGs (summarized to yield
VDGs scores) were markedly decreased in post-treatment biopsies compared with pre
treatment baselines. In contrast, VDGs scores were not significantly altered
following bevacizumab treatment in patients with stable or progressive disease.
Analysis of VDGs in ovarian cancer showed that VDGs as a prognostic signature was
able to predict patient outcome. Correlation estimation of VDGs scores and
molecular features revealed that VDGs was overrepresented in mesenchymal subtype
and BRCA mutation carriers. These findings highlighted the prognostic role of
VEGF-mediated angiogenesis in ovarian cancer, and proposed a VEGF-dependent gene
signature as a molecular basis for developing novel diagnostic strategies to aid
patient selection for VEGF-targeted agents.
PMID- 27498765
TI - HIV: A recipe for inducing broadly neutralizing antibodies.
PMID- 27498764
TI - Regulation of proinflammatory genes by the circulating microRNA hsa-miR-939.
AB - Circulating microRNAs are beneficial biomarkers because of their stability and
dysregulation in diseases. Here we sought to determine the role of miR-939, a
miRNA downregulated in patients with complex regional pain syndrome (CRPS). Hsa
miR-939 is predicted to target several proinflammatory genes, including IL-6,
VEGFA, TNFalpha, NFkappaB2, and nitric oxide synthase 2 (NOS2A). Binding of miR
939 to the 3' untranslated region of these genes was confirmed by reporter assay.
Overexpression of miR-939 in vitro resulted in reduction of IL-6, NOS2A and
NFkappaB2 mRNAs, IL-6, VEGFA, and NOS2 proteins and NFkappaB activation. We
observed a significant decrease in the NOS substrate l-arginine in plasma from
CRPS patients, suggesting reduced miR-939 levels may contribute to an increase in
endogenous NOS2A levels and NO, and thereby to pain and inflammation. Pathway
analysis showed that miR-939 represents a critical regulatory node in a network
of inflammatory mediators. Collectively, our data suggest that miR-939 may
regulate multiple proinflammatory genes and that downregulation of miR-939 in
CRPS patients may increase expression of these genes, resulting in amplification
of the inflammatory pain signal transduction cascade. Circulating miRNAs may
function as crucial signaling nodes, and small changes in miRNA levels may
influence target gene expression and thus disease.
PMID- 27498767
TI - AMP-activated protein kinase activator, HL156A reduces thioacetamide-induced
liver fibrosis in mice and inhibits the activation of cultured hepatic stellate
cells and macrophages.
AB - Cirrhosis, the end-stage of hepatic fibrosis, is not only life-threatening by
itself, but also a causative factor of liver cancer. Despite efforts to develop
treatment for liver fibrosis, there are no approved agents as anti-fibrotic drugs
to date. In the present study, we aimed to investigate the anti-fibrotic effect
of the AMP-activated protein kinase (AMPK) activator, HL156A. A mouse model of
thioacetamide (TAA)-induced liver fibrosis was used to examine the effect of
HL156A in vivo. Mice received either TAA alone or a combination of TAA and HL156A
intraperitoneally for a total duration of 6 weeks. Including HL156A during
exposure to TAA significantly reduced extracellular matrix (ECM) deposition and
production of the hepatic transforming growth factor-beta1 (TGF-beta1).
Immunohistochemical analysis revealed that the activation of hepatic stellate
cells and the capillarization of liver sinusoids were also diminished
significantly by HL156A co-treatment. The anti-fibrotic effect of HL156A was
further studied in vitro by using a rat hepatic stellate cell line, HSC-T6 cells.
The induction of alpha-smooth muscle actin (alpha-SMA) by TGF-beta1 treatment was
reversed by HL156A, which was likely via the activation of AMPK. Moreover, HL156A
showed anti-inflammatory effects on macrophages. Treatment with HL156A diminished
LPS-induced activation of both Raw264.7 macrophage cells and primary cultured
mouse macrophages. Taken together, these results imply that the AMPK activator
HL156A inhibits hepatic fibrosis via multiple mechanisms and could be a
potentially effective agent for fibrosis treatment.
PMID- 27498766
TI - Immunological aspects of intestinal mucus and mucins.
AB - A number of mechanisms ensure that the intestine is protected from pathogens and
also against our own intestinal microbiota. The outermost of these is the
secreted mucus, which entraps bacteria and prevents their translocation into the
tissue. Mucus contains many immunomodulatory molecules and is largely produced by
the goblet cells. These cells are highly responsive to the signals they receive
from the immune system and are also able to deliver antigens from the lumen to
dendritic cells in the lamina propria. In this Review, we will give a basic
overview of mucus, mucins and goblet cells, and explain how each of these
contributes to immune regulation in the intestine.
PMID- 27498768
TI - N-Terminal Peptide Detection with Optimized Peptide-Spectrum Matching and
Streamlined Sequence Libraries.
AB - We identified tryptic peptides in yeast cell lysates that map to translation
initiation sites downstream of the annotated start sites using the peptide
spectrum matching algorithms OMSSA and Mascot. To increase the accuracy of
peptide-spectrum matching, both algorithms were run using several standardized
parameter sets, and Mascot was run utilizing a, b, and y ions from collision
induced dissociation. A large fraction (22%) of the detected N-terminal peptides
mapped to translation initiation downstream of the annotated initiation sites.
Expression of several truncated proteins from downstream initiation in the same
reading frame as the full-length protein (frame 1) was verified by western
analysis. To facilitate analysis of the larger proteome of Drosophila, we created
a streamlined sequence library from which all duplicated trypsin fragments had
been removed. OMSSA assessment using this "stripped" library revealed 171
peptides that map to downstream translation initiation sites, 76% of which are in
the same reading frame as the full-length annotated proteins, although some are
in different reading frames creating new protein sequences not in the annotated
proteome. Sequences surrounding implicated downstream AUG start codons are
associated with nucleotide preferences with a pronounced three-base periodicity
N1^G2^A3.
PMID- 27498769
TI - Simplified three-dimensional tissue clearing and incorporation of colorimetric
phenotyping.
AB - Tissue clearing methods promise to provide exquisite three-dimensional imaging
information; however, there is a need for simplified methods for lower resource
settings and for non-fluorescence based phenotyping to enable light microscopic
imaging modalities. Here we describe the simplified CLARITY method (SCM) for
tissue clearing that preserves epitopes of interest. We imaged the resulting
tissues using light sheet microscopy to generate rapid 3D reconstructions of
entire tissues and organs. In addition, to enable clearing and 3D tissue imaging
with light microscopy methods, we developed a colorimetric, non-fluorescent
method for specifically labeling cleared tissues based on horseradish peroxidase
conversion of diaminobenzidine to a colored insoluble product. The methods we
describe here are portable and can be accomplished at low cost, and can allow
light microscopic imaging of cleared tissues, thus enabling tissue clearing and
imaging in a wide variety of settings.
PMID- 27498771
TI - [Corrigendum] VEGF in nuclear medicine: Clinical application in cancer and future
perspectives (Review).
AB - Following the publication of this article, after having re-examined our
manuscript, we noted an error in the acknowledgements section, as regards the
funding of our study. The correct version of acknowledgements section is shown
below: Acknowledgements This study was supported by the Ministry of Health and
Fondazione Roma and by NOBILE S.p.A. Thanks are also due to REGIONE LAZIO Prot.
FILAS-RU-2014 - 1020 (E.A.). [the original article was published in the
International Journal of Oncology 49: 437-447, 2016; DOI: 10.3892/ijo.2016.3553].
PMID- 27498770
TI - Alkaloid-Catalyzed Enantioselective [3 + 2] Cycloaddition of Ketenes and
Azomethine Imines.
AB - A new asymmetric synthesis of bicyclic pyrazolidinones through an alkaloid
catalyzed formal [3 + 2] cycloaddition of in situ generated ketenes and
azomethine imines is described. The products were formed in good to excellent
yields (52-99% for 17 examples), with good to excellent diastereoselectivity (dr
5:1 to 27:1 for 11 examples), and with excellent enantioselectivity in all cases
(>=96% ee). This method represents the first unambiguous example of an
enantioselective reaction between ketenes and a 1,3-dipole.
PMID- 27498772
TI - Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast
cells, and subsequently blocking PKCepsilon-dependent activation of TRPV1.
AB - AIM: Severe painful sensory neuropathy often occurs during paclitaxel
chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas
quercetin, a polyphenolic flavonoid contained in various plants, which can
specifically inhibit histamine release as a mast cell stabilizer. In this study
we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain
and elucidated the underlying mechanisms. METHODS: Quercetin inhibition on
histamine release was validated in vitro by detecting histamine release from rat
basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 MUmol/L). In
the in vivo experiments, rats and mice received quercetin (20, 40 mg.kg(-1).d(
1)) for 40 and 12 d, respectively. Meanwhile, the animals were injected with
paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and
mechanical allodynia were evaluated at the different time points. The animals
were euthanized and spinal cords and dorsal root ganglions were harvested for
analyzing PKCepsilon and TRPV1 expression levels. The plasma histamine levels
were assessed in rats on d 31. RESULTS: Pretreatment with quercetin (3, 10, 30
MUmol/L) dose-dependently inhibited excessive histamine release from paclitaxel
stimulated RBL-2H3 cells in vitro, and quercetin administration significantly
suppressed the high plasma histamine levels in paclitaxel-treated rats. Quercetin
administration dose-dependently raised the thresholds for heat hyperalgesia and
mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin
administration dose-dependently suppressed the increased expression levels of
PKCepsilon and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and
mice. Moreover, quercetin administration may inhibited the translocation of
PKCepsilon from the cytoplasm to the membrane in the spinal cord and DRG of
paclitaxel-treated rats. CONCLUSION: Our results reveal the underlying mechanisms
of paclitaxel-induced peripheral neuropathy and demonstrate the therapeutic
potential of quercetin for treating this side effect.
PMID- 27498773
TI - DL0410, a novel dual cholinesterase inhibitor, protects mouse brains against
Abeta-induced neuronal damage via the Akt/JNK signaling pathway.
AB - AIM: 1,1'-([1,1'-Biphenyl]-4,4'-diyl)bis(3-(piperidin-1-yl)propan-1
one)dihydrochloride (DL0410) is a novel synthetic dual acetylcholinesterase
(AChE)/butyrocholinesterase (BuChE) inhibitor, which has shown a potential
therapeutic effect on Alzheimer's disease (AD). In this study we examined whether
DL0410 produced neuroprotective effects in an AD cellular model and an Abeta1-42
induced amnesia mouse model. METHODS: The in vitro inhibitory activities against
AChE and BuChE were estimated using Ellman's assay. Copper-induced toxicity in
APPsw-SY5Y cells was used as AD cellular model, the cell viability was assessed
using MTS assay, and cell apoptosis was evaluated based on mitochondrial membrane
potential detection. Abeta1-42-induced amnesia mouse model was made in male mice
by injecting aggregated Abeta1-42 (2 MUg in 2 MUL 0.1% DMSO) into the right
cerebral ventricle. Before and after Abeta1-42 injection, the mice were orally
administered DL0410 (1, 3, 9 mg.kg-1.d-1) or rivastigmine (2 mg.kg-1.d-1) for 3
and 11 d, respectively. Memory impairments were examined using Morris water maze
(MWM) test and passive avoidance test. The expression levels of APP, CREB, BDNF,
JNK and Akt in the mouse brains were measured with either immunohistochemistry or
Western blotting. RESULTS: DL0410 exhibited in vitro inhibitory abilities against
AChE and BuChE with IC50 values of 0.286+/-0.004 and 3.962+/-0.099 MUmol/L,
respectively, which were comparable to those of donepezil and rivastigmine. In
APPsw-SY5Y cells, pretreatment with DL0410 (1, 3, and 10 MUmol/L) decreased the
phosphorylation of JNK and increased the phosphorylation of Akt, markedly
decreased copper-stimulated Abeta1-42 production, reversed the loss of
mitochondrial membrane potential, and dose-dependently increased the cell
viability. In Abeta1-42-treated mice, DL0410 administration significantly
ameliorated learning and memory deficits in MWM test and passive avoidance test.
Furthermore, DL0410 administration markedly decreased Abeta1-40/42 deposits in
mouse cerebral cortices, and significantly up-regulated neurotrophic CREB/BDNF.
Meanwhile, Akt/JNK signaling pathway may play a key role in the neuroprotective
effect of DL0410. CONCLUSION: DL0410 ameliorates cognitive deficit and exerts
neuronal protection in AD models, implicating this compound as a candidate drug
for the prevention and therapy of AD.
PMID- 27498774
TI - Acetylcholinesterase-independent protective effects of huperzine A against iron
overload-induced oxidative damage and aberrant iron metabolism signaling in rat
cortical neurons.
AB - AIM: Iron dyshomeostasis is one of the primary causes of neuronal death in
Alzheimer's disease (AD). Huperzine A (HupA), a natural inhibitor of
acetylcholinesterase (AChE), is a licensed anti-AD drug in China and a
nutraceutical in the United Sates. Here, we investigated the protective effects
of HupA against iron overload-induced injury in neurons. METHODS: Rat cortical
neurons were treated with ferric ammonium citrate (FAC), and cell viability was
assessed with MTT assays. Reactive oxygen species (ROS) assays and adenosine
triphosphate (ATP) assays were performed to assess mitochondrial function. The
labile iron pool (LIP) level, cytosolic-aconitase (c-aconitase) activity and iron
uptake protein expression were measured to determine iron metabolism changes. The
modified Ellman's method was used to evaluate AChE activity. RESULTS: HupA
significantly attenuated the iron overload-induced decrease in neuronal cell
viability. This neuroprotective effect of HupA occurred concurrently with a
decrease in ROS and an increase in ATP. Moreover, HupA treatment significantly
blocked the upregulation of the LIP level and other aberrant iron metabolism
changes induced by iron overload. Additionally, another specific AChE inhibitor,
donepezil (Don), at a concentration that caused AChE inhibition equivalent to
that of HupA negatively, influenced the aberrant changes in ROS, ATP or LIP that
were induced by excessive iron. CONCLUSION: We provide the first demonstration of
the protective effects of HupA against iron overload-induced neuronal damage.
This beneficial role of HupA may be attributed to its attenuation of oxidative
stress and mitochondrial dysfunction and elevation of LIP, and these effects are
not associated with its AChE-inhibiting effect.
PMID- 27498775
TI - The structural basis of the dominant negative phenotype of the
Galphai1beta1gamma2 G203A/A326S heterotrimer.
AB - AIM: Dominant negative mutant G proteins have provided critical insight into the
mechanisms of G protein-coupled receptor (GPCR) signaling, but the mechanisms
underlying the dominant negative characteristics are not completely understood.
The aim of this study was to determine the structure of the dominant negative
Galphai1beta1gamma2 G203A/A326S complex (Gi-DN) and to reveal the structural
basis of the mutation-induced phenotype of Galphai1beta1gamma2. METHODS: The
three subunits of the Gi-DN complex were co-expressed with a baculovirus
expression system. The Gi-DN heterotrimer was purified, and the structure of its
complex with GDP was determined through X-ray crystallography. RESULTS: The Gi-DN
heterotrimer structure revealed a dual mechanism underlying the dominant negative
characteristics. The mutations weakened the hydrogen bonding network between
GDP/GTP and the binding pocket residues, and increased the interactions in the
Galpha-Gbetagamma interface. Concomitantly, the Gi-DN heterotrimer adopted a
conformation, in which the C-terminus of Galphai and the N-termini of both the
Gbeta and Ggamma subunits were more similar to the GPCR-bound state compared with
the wild type complex. From these structural observations, two additional
mutations (T48F and D272F) were designed that completely abolish the GDP binding
of the Gi-DN heterotrimer. CONCLUSION: Overall, the results suggest that the
mutations impede guanine nucleotide binding and Galpha-Gbetagamma protein
dissociation and favor the formation of the G protein/GPCR complex, thus blocking
signal propagation. In addition, the structure provides a rationale for the
design of other mutations that cause dominant negative effects in the G protein,
as exemplified by the T48F and D272F mutations.
PMID- 27498776
TI - The POR rs1057868-rs2868177 GC-GT diplotype is associated with high tacrolimus
concentrations in early post-renal transplant recipients.
AB - AIM: Cytochrome P450 oxidoreductase (POR) is the only flavoprotein that donates
electrons to all microsomal P450 enzymes (CYP), and several POR SNPs have been
shown to be important contributors to altered CYP activity or CYP-mediated drug
metabolism. In this study we examined the association between 6 POR SNPs and
tacrolimus concentrations in Chinese renal transplant recipients. METHODS: A
total of 154 renal transplant recipients were enrolled. Genotyping of CYP3A5*3
and 6 POR SNPs was performed. All patients received a triple immunosuppressive
regimen comprising tacrolimus, mycophenolate mofetil and prednisone. Dose
adjusted tacrolimus trough concentrations were obtained on d 7 (C0D7/D) after
transplantation when steady-state concentration of tacrolimus was achieved
(dosage had been unchanged for more than 3 d). RESULTS: Tacrolimus C0D7/D in
CYP3A5*3/*3/ POR rs1057868-rs2868177 GC-GT diplotype carriers was 1.62- and 2.72
fold higher than those in CYP3A5*3/*3/ POR rs1057868-rs2868177 GC-GT diplotype
non-carriers and CYP3A5*1 carriers (220.17+/-48.09 vs 135.69+/-6.86 and 80.84+/
5.27 ng/mL/mg/kg, respectively, P<0.0001). Of CYP3A5*3/*3/ POR rs1057868
rs2868177GC-GT diplotype carriers, 85.71% exceeded the upper limit of the target
range (8 ng/mL), which was also significantly higher compared with the latter two
groups (14.29% and 0.00%, respectively, P<0.0001). The CYP3A5*3 and POR rs1057868
rs2868177 GC-GT diplotype explained 31.7% and 5.7%, respectively, of the inter
individual variability of tacrolimus C0D7/D, whereas the POR rs1057868-rs2868177
GC-GT diplotype could explain 10.9% of the inter-individual variability of
tacrolimus C0D7/D in CYP3A5 non-expressers. CONCLUSION: The CYP3A5*3 and POR
rs1057868-rs2868177 GC-GT diplotype accounted for the inter-individual variation
of tacrolimus C0D7/D. Genotyping of POR rs1057868-rs2868177 diplotypes would help
to differentiate initial tacrolimus dose requirements and to achieve early target
C0 ranges in Chinese renal transplant recipients.
PMID- 27498777
TI - Vitamin K2 suppresses rotenone-induced microglial activation in vitro.
AB - AIM: Increasing evidence has shown that environmental factors such as rotenone
and paraquat induce neuroinflammation, which contributes to the pathogenesis of
Parkinson's disease (PD). In this study, we investigated the molecular mechanisms
underlying the repression by menaquinone-4 (MK-4), a subtype of vitamin K2, of
rotenone-induced microglial activation in vitro. METHODS: A microglial cell line
(BV2) was exposed to rotenone (1 MUmol/L) with or without MK-4 treatment. The
levels of TNF-alpha or IL-1beta in 100 MUL of cultured media of BV2 cells were
measured using ELISA kits. BV2 cells treated with rotenone with or without MK4
were subjected to mitochondrial membrane potential, ROS production,
immunofluorescence or immunoblot assays. The neuroblastoma SH-SY5Y cells were
treated with conditioned media (CM) of BV2 cells that were exposed to rotenone
with or without MK-4 treatment, and the cell viability was assessed using MTT
assay. RESULTS: In rotenone-treated BV2 cells, MK-4 (0.5-20 MUmol/L) dose
dependently suppressed the upregulation in the expression of iNOS and COX-2 in
the cells, as well as the production of TNF-alpha and IL-1beta in the cultured
media. MK-4 (5-20 MUmol/L) significantly inhibited rotenone-induced nuclear
translocation of NF-kappaB in BV2 cells. MK-4 (5-20 MUmol/L) significantly
inhibited rotenone-induced p38 activation, ROS production, and caspase-1
activation in BV2 cells. MK-4 (5-20 MUmol/L) also restored the mitochondrial
membrane potential that had been damaged by rotenone. Exposure to CM from
rotenone-treated BV2 cells markedly decreased the viability of SH-SY5Y cells.
However, this rotenone-activated microglia-mediated death of SH-SY5Y cells was
significantly attenuated when the BV2 cells were co-treated with MK-4 (5-20
MUmol/L). CONCLUSION: Vitamin K2 can directly suppress rotenone-induced
activation of microglial BV2 cells in vitro by repressing ROS production and p38
activation.
PMID- 27498778
TI - Ethanol inhibits histaminergic neurons in mouse tuberomammillary nucleus slices
via potentiating GABAergic transmission onto the neurons at both pre- and
postsynaptic sites.
AB - AIM: Ethanol, one of the most frequently used and abused substances in our
society, has a profound impact on sedation. However, the neuronal mechanisms
underlying its sedative effect remain unclear. In this study, we investigated the
effects of ethanol on histaminergic neurons in the tuberomammillary nucleus
(TMN), a brain region thought to be critical for wakefulness. METHODS: Coronal
brain slices (250 MUm thick) containing the TMN were prepared from GAD67-GFP
knock-in mice. GAD67-GFP was used to identify histaminergic neurons in the TMN.
The spontaneous firing and membrane potential of histaminergic neurons, and
GABAergic transmission onto these neurons were recorded using whole-cell patch
clamp recordings. Drugs were applied through superfusion. RESULTS: Histaminergic
and GAD67-expressing neurons in the TMN of GAD67-GFP mice were highly co
localized. TMN GFP-positive neurons exhibited a regular spontaneous discharge at
a rate of 2-4 Hz without burst firing. Brief superfusion of ethanol (64, 190, and
560 mmol/L) dose-dependently and reversibly suppressed the spontaneous firing of
the neurons in the TMN; when synaptic transmission was blocked by tetrodotoxin (1
MUmol/L), ethanol caused hyperpolarization of the membrane potential.
Furthermore, superfusion of ethanol markedly increased the frequency and
amplitude of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs
and mIPSCs), which were abolished in the presence of the GABAA receptor
antagonist bicuculline (20 MUmol/L). Finally, ethanol-mediated enhancement of
sIPSCs and mIPSCs was significantly attenuated when the slices were pretreated
with the GABAB agonist baclofen (30 MUmol/L). CONCLUSION: Ethanol inhibits the
excitability of histaminergic neurons in mouse TMN slices, possibly via
potentiating GABAergic transmission onto the neurons at both pre- and
postsynaptic sites.
PMID- 27498779
TI - Sweroside ameliorates alpha-naphthylisothiocyanate-induced cholestatic liver
injury in mice by regulating bile acids and suppressing pro-inflammatory
responses.
AB - AIM: Sweroside is an iridoid glycoside with diverse biological activities. In the
present study we investigated the effects of sweroside on alpha
naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in mice. METHODS:
Mice received sweroside (120 mg.kg(-1).d(-1), ig) or a positive control INT-747
(12 mg.kg(-1).d(-1), ig) for 5 d, and ANIT (75 mg/kg, ig) was administered on d
3. The mice were euthanized on d 5, and serum biochemical markers, hepatic bile
acids and histological changes were analyzed. Hepatic expression of genes related
to pro-inflammatory mediators and bile acid metabolism was also assessed. Primary
mouse hepatocytes were exposed to a reconstituted mixture of hepatic bile acids,
which were markedly elevated in the ANIT-treated mice, and the cell viability and
expression of genes related to pro-inflammatory mediators were examined. RESULTS:
Administration of sweroside or INT-747 effectively ameliorated ANIT-induced
cholestatic liver injury in mice, as evidenced by significantly reduced serum
biochemical markers and attenuated pathological changes in liver tissues.
Furthermore, administration of sweroside or INT-747 significantly decreased ANIT
induced elevation of individual hepatic bile acids, such as beta-MCA, CA, and
TCA, which were related to its effects on the expression of genes responsible for
bile acid synthesis and transport as well as pro-inflammatory responses.
Treatment of mouse hepatocytes with the reconstituted bile acid mixture induced
significant pro-inflammatory responses without affecting the cell viability.
CONCLUSION: Sweroside attenuates ANIT-induced cholestatic liver injury in mice by
restoring bile acid synthesis and transport to their normal levels, as well as
suppressing pro-inflammatory responses.
PMID- 27498781
TI - Synthetic Chlorins, Possible Surrogates for Chlorophylls, Prepared by
Derivatization of Porphyrins.
AB - Chlorophylls make Earth green, are the central constituents in the engine of
photosynthesis, and not surprisingly have garnered immense attention. A chlorin,
the core chromophore of a chlorophyll, is a dihydroporphyrin macrocycle that
contains one pyrroline ring and three pyrrole rings. The dominant method for the
synthesis of chlorins has entailed the derivatization of porphyrins. The present
review covers the ostensibly simple conversion of porphyrins, regardless of
synthetic or biological origin, to chlorins. The period covered encompasses the
entire history since the beginnings of chlorin synthetic chemistry in the early
20th century through 2015. Representative transformations include hydrogenation,
cycloaddition, annulation, and diverse "breaking and mending" approaches.
Altogether, the synthesis of >1000 chlorins or chlorin-like compounds (containing
>50 distinct pyrroline motifs) is described. Such diversity animates the question
"what structural features are essential for a chlorin to resemble chlorophyll?"
To begin to address the structure-spectrum relationship, > 250 absorption spectra
are provided for representative structures. The synthesis and spectral properties
of the vast collection of compounds described herein are expected to illuminate
the scope to which synthetic chlorins can serve as surrogates for chlorophylls
and be exploited in diverse ways.
PMID- 27498780
TI - Effects of linagliptin and liraglutide on glucose- and angiotensin II-induced
collagen formation and cytoskeleton degradation in cardiac fibroblasts in vitro.
AB - AIM: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4)
inhibitors can not only lower blood glucose levels, but also alleviate cardiac
remodeling after myocardial ischemia and hypertension. In the present study, we
investigated the effects of a DPP-4 inhibitor (linagliptin) and a GLP-1 activator
(liraglutide) on glucose- and angiotensin II (Ang II)-induced collagen formation
and cytoskeleton reorganization in cardiac fibroblasts in vitro, and elucidated
the related mechanisms. METHODS: Cardiac fibroblasts were isolated from the
hearts of 6-week-old C57BL/6 mice, and then exposed to different concentrations
of glucose or Ang II for 24 h. The expression of fibrotic signals (fibronectin,
collagen-1, -3 and -4), as well as ERK1/2 and NF-kappaB-p65 in the fibroblasts
was examined using Western blotting assays. F-actin degradation was detected
under inverted laser confocal microscope in fibroblasts stained with Rhodamine
phalloidin. RESULTS: Glucose (1-40 mmol/L) and Ang II (10-8-10-5 mol/L) dose
dependently increased the expression of fibronectin, collagens, phospho-ERK1/2
and phospho-NF-kappaB-p65 in cardiac fibroblasts. High concentrations of glucose
(>=40 mmol/L) and Ang II (>=10-6 mol/L) caused a significant degradation of F
actin (less assembly F-actin fibers and more disassembly fibers). ERK1/2
inhibitor U0126 (10 MUmol/L) and NF-kappaB inhibitor JSH-23 (10 MUmol/L) both
markedly suppressed glucose- and angiotensin II-induced fibronectin and collagen
expressions in cardiac fibroblasts. Furthermore, pretreatment with liraglutide
(10-100 nmol/L) or linagliptin (3 and 30 nmol/L) significantly decreased glucose-
and Ang II-induced expression of fibrotic signals, phospho-ERK1/2 and phospho-NF
kappaB-p65 in cardiac fibroblasts. Moreover, pretreatment with liraglutide (30
nmol/L) or liraglutide (100 nmol/L) markedly inhibited glucose-induced F-actin
degradation, however, only liraglutide inhibited Ang II-induced F-actin
degradation. CONCLUSION: Linagliptin and liraglutide inhibit glucose- and Ang II
induced collagen formation in cardiac fibroblasts via activation of the ERK/NF
kappaB/pathway. Linagliptin and liraglutide also markedly inhibit glucose-induced
F-actin degradation in cardiac fibroblasts, but only liraglutide inhibits Ang II
induced F-actin degradation.
PMID- 27498782
TI - Decreased LIPF expression is correlated with DGKA and predicts poor outcome of
gastric cancer.
AB - Gastric cancer (GC) is a common and deadly digestive tract tumor worldwide.
Unfortunately, diagnosis of GC is usually confused and misleading because of
atypical symptoms or incomplete complaints. Accordingly, exploring gene
expression profile and identifying genes with analogical variance trend will
bring new perspective into the diagnosis and treatment of GC. Herein, a RNA-Seq
dataset from Caucasian GC and their matched non-cancerous samples [Gene
Expression Omnibus (GEO): SRP049809] and datasets from four microarrays
constituted with tumor and non-tumor tissues (GEO: GSE13911, GSE19826, GSE29272,
GSE33335) were analyzed to explore the differentially expressed genes (DGEs). As
a result, we identified a core set of 373 DGEs. Among these genes, we found that
most downregulated genes were related to lipid-metabolic functions. Especially,
the gastric lipase (LIPF) gene, which was connected with various lipid metabolism
processes, was significantly decreased among all datasets. We then performed
immunohistochemistry experiments using gastric tissue arrays to investigate the
clinical effects, and the expression of a LIPF target gene, diacylglycerol kinase
alpha (DGKA). Among the 90 samples of gastric adenocarcinoma, the LIPF and DGKA
levels were both decreased in cancer tissues [LIPF, 59.1% (53/90); DGKA, 77.8%
(70/90)] compared to normal tissues [LIPF, 94.4% (85/90); DGKA, 90% (81/90)]. The
expression level of these two proteins in GC was associated with local invasion
and disease stage. Cox regression identified high DGKA expression (HR, 0.49; 95%
CI, 0.26-0.94; P=0.03) as a predictor of good prognosis and LNM status (HR, 4.63;
95% CI, 1.39-15.51; P=0.01) as a predictor of poor prognosis. Thus we speculated
that LIPF-DGKA might serve as a potential possible biomarkers for diagnosis of
GC, and their downregulation may bring new perspective into the investigation of
GC prognosis.
PMID- 27498783
TI - Exceptional gravimetric and volumetric CO2 uptake in a palladated NbO-type MOF
utilizing cooperative acidic and basic, metal-CO2 interactions.
AB - A novel NbO-type MOF is reported based on a palladated organic linker, showing a
remarkable gravimetric and volumetric CO2 uptake, reaching 201.8 cm(3) g(-1) (9.0
mmol g(-1), 39.7 wt%) and 187.8 cm(3) cm(-3) at 273 K and 1 bar, respectively.
Accurate theoretical calculations revealed that the exceptional CO2 uptake is due
to the combination of Lewis base Pd(ii)-CO2 (24.3 kJ mol(-1)) and Lewis acid
Cu(ii)-CO2 (30.3 kJ mol(-1)) interactions, as well as synergistic pore size
effects.
PMID- 27498784
TI - Functional characterization of GmBZL2 (AtBZR1 like gene) reveals the conserved BR
signaling regulation in Glycine max.
AB - Brassinosteroids (BRs) play key roles in plant growth and development, and
regulate various agricultural traits. Enhanced BR signaling leads to increased
seed number and yield in Arabidopsis bzr1-1D (AtBZR1(P234L), gain-of-function
mutant of the important transcription factor in BR signaling/effects). BR signal
transduction pathway is well elucidated in Arabidopsis but less known in other
species. Soybean is an important dicot crop producing edible oil and protein.
Phylogenetic analysis reveals AtBZR1-like genes are highly conserved in
angiosperm and there are 4 orthologues in soybean (GmBZL1-4). We here report the
functional characterization of GmBZL2 (relatively highly expresses in flowers).
The P234 site in AtBZR1 is conserved in GmBZL2 (P216) and mutation of
GmBZL2(P216L) leads to GmBZL2 accumulation. GmBZL2(P216L) (GmBZL2*) in
Arabidopsis results in enhanced BR signaling; including increased seed number per
silique. GmBZL2* partially rescued the defects of bri1-5, further demonstrating
the conserved function of GmBZL2 with AtBZR1. BR treatment promotes the
accumulation, nuclear localization and dephosphorylation/phosphorylation ratio of
GmBZL2, revealing that GmBZL2 activity is regulated conservatively by BR
signaling. Our studies not only indicate the conserved regulatory mechanism of
GmBZL2 and BR signaling pathway in soybean, but also suggest the potential
application of GmBZL2 in soybean seed yield.
PMID- 27498785
TI - Clinical effects of miR-101 on prognosis of hepatocellular carcinoma and
carcinogenic mechanism of anti-miR-101.
AB - The aim of this study was to verify whether anti-miR-101 participates in the
treatment of hepatocellular carcinoma (HCC) as a small-molecule antitumor agent,
and to explore the effect on phosphatase and tensin homolog deleted on chromosome
10 (PTEN). Patients who received consecutive hepatectomies were followed-up, and
miR-101 expressions in their tumor and paracancerous tissues were detected.
Correlation between miR-101 expression and clinical pathological factors and
prognosis was studied. High-throughput sequencing was used to detect the genetic
and microRNA (miRNA) levels of tumor tissues. Expression of anti-miR-101 in
different HCC cell lines was determined, and those of desired genes and proteins
were detected by qRT-PCR and western blotting to obtain the target gene. miR-101
was significantly upregulated in HCC patients compared with that in paracancerous
tissues. High miR-101 expression, vascular invasion, tumor size >=7 cm and late
pathological stage were the risk factors of recurrence-free survival rate. High
miR-101 expression was the independent prognostic factor of total and recurrence
free survival rates. CXCL12, IL6R, FOXO3 and PTEN were screened as desired genes,
and only PTEN was expressed significantly differently in three cell lines. miR
101 could bind 3'-UTR of WT-PTEN with reduced fluorescent intensity, suggesting
that PTEN was the target gene. SMMC-7721, HepG2 and Huh7 were eligible cell lines
for miR-101 studies. miR-101 was an applicable molecular marker of HCC. Anti-miR
101 regulated the transcription of PTEN and may promote cell proliferation,
differentiation and apoptosis by regulating downstream genes with PTEN. The
regulatory effects of anti-miR-101 on PTEN provide valuable evidence for finding
novel miRNA drugs.
PMID- 27498786
TI - Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by
targeting the PI3K/AKT/mTOR signaling pathway.
AB - Recent studies have demonstrated that nitidine chloride (NC), a natural bioactive
alkaloid, displays potent antitumor activity in various types of cancer. In the
present study, NC was examined for efficacy in the treatment of human
glioblastoma multiforme (GBM) as well as the molecular basis for its more general
inhibitory effects in cancer. U251 and U87 GBM cell lines were exposed to three
concentrations of NC (5, 25 and 50 uM) in vitro, and tumor cell growth was
assessed on the basis of proliferation, migration and energy metabolism.
Decreases in viability and proliferation reached ~50% for both cell lines with 50
uM NC at 24 h as assessed by cell viability Cell Counting Kit-8 (CCK-8) and EdU
assays. In wound closure and Transwell assays, migration and invasion were
inhibited at 50 uM after 24 h (~20 and 80%, respectively; P<0.05). ATP and L
lactate levels were also decreased after treatment with NC (50 uM, 24 h; P<0.05
and P<0.01, respectively). Finally, in western blot analysis, phosphorylation of
Akt and mTOR was suppressed by NC, but partially restored when cells were treated
simultaneously with a novel Akt activator, SC79. Partial restoration was also
observed in viability/proliferation (U251 and U87, ~15 vs. 40%; NC vs. NC + SC79;
P<0.05) and invasion (U251 and U87, ~30 vs. 60%; NC vs. NC + SC79; P<0.05). Our
results demonstrated that NC inhibits development of GBM by targeting the
PI3K/Akt/mTOR signaling pathway and provides a potential therapeutic agent for
the treatment of GBM.
PMID- 27498787
TI - MicroRNA-140 represses glioma growth and metastasis by directly targeting ADAM9.
AB - Glioma is the most frequent primary malignant tumor of the human brain. Recently,
great progress has been made in the combined therapy of glioma. However, the
clinical effects of these treatments and prognosis for patients with glioma
remains poor. MicroRNAs (miRNAs) have been demonstrated to play important roles
in the initiation and progression of various types of human cancers, also
including glioma. The present study investigated the expression patterns of
microRNA-140 (miR-140) in glioma, and the roles of miR-140 in glioma cell
proliferation, migration and invasion. The results showed that miR-140 was
significantly downreuglated in glioma tissues and cell lines, and low expression
levels of miR-140 were correlated with World Health Organization (WHO) grade and
Karnofsky performance score (KPS) of glioma patients. Restoration of miR-140
obviously suppressed glioma cell proliferation, migration and invasion. In
addition, a disintegrin and metalloproteinase 9 (ADAM9) was identified as a novel
direct target gene of miR-140 in glioma. Furthermore, knockdown of ADAM9
simulated the tumor suppressor functions of miR-140, while overexpression of
ADAM9 abrogated these suppressive effects induced by miR-140 in glioma cells. In
conclusion, the present study demonstrated the expression and clinical roles of
miR-140 in glioma and suggested that miR-140 inhibited proliferation, migration
and invasion of glioma cells, partially at least via suppressing ADAM9
expression. Therefore, miR-140 may be a novel candidate target for the
development of therapeutic strategies for patients with glioma.
PMID- 27498788
TI - Taxonomic reassessment of the genus Elizabethkingia using whole-genome
sequencing: Elizabethkingia endophytica Kampfer et al. 2015 is a later subjective
synonym of Elizabethkingia anophelis Kampfer et al. 2011.
AB - The taxonomic status of all species of the genus Elizabethkingia was re-evaluated
by comparative genomics based on whole-genome sequencing. From these results it
is clear that Elizabethkingia endophytica is a later subjective synonym of
Elizabethkingia anophelis. In addition, genome-based analysis revealed the
misidentification of isolates previously identified by traditional approaches and
indicates the presence of two more species. We propose a more rapid
identification scheme on the basis of an in silico PCR assay derived from
comparative genomics of whole-genome sequences (WGS) from 29 well-curated
strains.
PMID- 27498789
TI - Mycoplasma hyopneumoniae does not affect the interferon-related anti-viral
response but predisposes the pig to a higher level of inflammation following
swine influenza virus infection.
AB - In pigs, influenza A viruses and Mycoplasma hyopneumoniae (Mhp) are major
contributors to the porcine respiratory disease complex. Pre-infection with Mhp
was previously shown experimentally to exacerbate the clinical outcomes of H1N1
infection during the first week after virus inoculation. In order to better
understand the interactions between these pathogens, we aimed to assess very
early responses (at 5, 24 and 48 h) after H1N1 infection in pigs pre-infected or
not with Mhp. Clinical signs and macroscopic lung lesions were similar in both
infected groups at early times post-H1N1 infection; and Mhp pre-infection
affected neither the influenza virus replication nor the IFN-induced antiviral
responses in the lung. However, it predisposed the animals to a higher
inflammatory response to H1N1 infection, as revealed by the massive infiltration
of neutrophils and macrophages into the lungs and the increased production of pro
inflammatory cytokines (IL-6, IL-1beta and TNF-alpha). Thus, it seems it is this
marked inflammatory state that would play a role in exacerbating the clinical
signs subsequent to H1N1 infection.
PMID- 27498790
TI - Paenibacillus solani sp. nov., isolated from potato rhizosphere soil.
AB - A novel Gram-stain-positive, endospore-forming bacterium, designated FJAT-22460T,
was isolated from a soil sample of a potato field in Xinjiang Autonomous Region,
China. Cells were rods that were catalase-positive and motile by peritrichous
flagella. The strain was found to grow at temperatures ranging from 10 to 40
degrees C (optimum 30 degrees C) and at pH 5.0-12.0 (optimum pH 7) with 0-5 %
(w/v) NaCl (optimum 0 % NaCl). Phylogenetic analysis based on 16S rRNA gene
sequences indicated that strain FJAT-22460T belonged to the genus Paenibacillus
and exhibited 16S rRNA gene sequence similarities of 97.3, 97.2, 97.2 and 97.0 %
with Paenibacillus glucanolyticus DSM 5162T, Paenibacillus lautus DSM 3035T,
Paenibacillus lactis MB 1871T and Paenibacillus chibensis JCM 9905T,
respectively. DNA-DNA relatedness of strain FJAT-22460T with Paenibacillus
glucanolyticusDSM 5162T and Paenibacillus lautus DSM 3035T was 62.6 % and 33.3 %,
respectively, lower than the 70 % accepted for species delineation. The
menaquinone was identified as MK-7. The major fatty acids detected were anteiso
C15 : 0 (51.4 %), iso-C15 : 0 (5.3 %), C16 : 0 (12.1 %), iso-C16 : 0 (10.7 %) and
anteiso-C17 : 0 (6.9 %). The DNA G+C content was determined to be 50.9 mol%.
Phenotypic, chemotaxonomic and genotypic properties clearly indicated that
isolate FJAT-22460T represents a novel species within the genus Paenibacillus,
for which the name Paenibacillus solani sp. nov. is proposed. The type strain is
FJAT-22460T (=DSM 100999T=CCTCC AB 2015207T).
PMID- 27498791
TI - Pontibacter rugosus sp. nov., isolated from seawater.
AB - A motile and rod-shaped bacterium, designated strain KYW1030T, was isolated from
seawater collected from the Gwangyang bay (Republic of Korea). Cells were Gram
reaction-negative, aerobic, catalase-positive and oxidase-negative. The major
fatty acids were summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), iso
C15 : 0 and iso-C17 : 0 3-OH. The strain contained MK-7 as the major isoprenoid
quinone, phosphatidylethanolamine and diphosphatidylglycerol as the major polar
lipids and sym-homospermidine as the major polyamine. The DNA G+C content was 46
mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain
KYW1030T forms an evolutionary lineage within the radiation enclosing the members
of the genus Pontibacter, with Pontibacterakesuensis AKS 1T (97.9 % 16S rRNA gene
sequence similarity) as its nearest neighbour. A number of phenotypic
characteristics distinguished strain KYW1030T from the related members of the
genus Pontibacter. On the basis of the evidence presented in this study, a novel
species, Pontibacter rugosus sp. nov., is proposed for strain KYW1030T (=KACC
18739T=JCM 31319T).
PMID- 27498792
TI - Use of Reproductive Microhabitat by Melanophryniscus montevidensis (Anura:
Bufonidae) from Uruguay.
AB - This study describes the reproductive microhabitat of Melanophryniscus
montevidensis and its use in two water bodies (WBs) in Barra de la Laguna de
Rocha, Uruguay. Monthly field trips were performed between March 2012 and
February 2013. Variables related to the WBs and vegetation, as well as parameters
linked to the usage the amphibians make of the site (e.g: distance to the border
of the pond, water depth and the vegetation use) were recorded. The behavior
shown by the individuals during the breeding activity was recorded. This activity
occurs in shallow temporary WBs with abundant hydrophilic vegetation. The
individuals were found more frequently in areas near the edge of the pond, which
has denser vegetation. The calling males were found closer to the border of the
pond, and they showed better body condition than the non-calling males. In
addition to calling activities, males used alternative tactics to find couples,
such as active search of females, and aggressive behaviors, such as male
displacing and physical combat. Such behaviors are common in anurans with
explosive reproductive dynamics. The characterization of the reproductive
microhabitats permits the proposal of strategies for the conservation of the
species in Uruguay, given that the loss and fragmentation of habitats is one of
the main causes considered for the decrease in their populations.
PMID- 27498793
TI - The Size of Winter-Flooded Paddy Fields No Longer Limits the Foraging Habitat Use
of the Endangered Crested Ibis (Nipponia nippon) in Winter.
AB - Paddy fields have traditionally been viewed as the key foraging habitats for the
endangered crested ibis (Nipponia nippon). With the population of this species
now increasing, its distribution has expanded to both lowland areas and outside
the nature reserve. However, little is known about the current foraging habitat
preferences of these birds, especially during winter. In this research, a total
of 54 used sites and 50 unused sites were investigated during winter from
December 2011 to January 2012. The results of logistic regression analysis
indicate that soil softness, human disturbance, and distance to the nearest road
were important factors. For the site plots of winter-flooded paddy fields, the
birds prefer the paddy fields with higher coverage of vegetation, except softer
foraging sites and lower human-related disturbance. In lowland areas, the size of
winter-flooded paddy fields was not a limiting factor, due to the availability of
other wetlands capable of providing abundant food. The micro-habitat
characteristics were important indicators of foraging habitat quality rather than
the size of winter-flooded paddy fields, and the food accessibility may play an
important role in the process of foraging habitat use. We suggest the improvement
of the foraging micro-habitat and environmental characteristics would be
effective in ensuring the availability of food in the dispersed lowland areas.
The local people still needed to be encouraged and compensated by their single
cropping cultivation, ploughed the paddy fields after harvesting and irrigated
them with shallow water flooded in the original core areas of the nature reserve.
PMID- 27498794
TI - Estimated Seed Shadow Generated by Japanese Martens(Martes melampus): Comparison
with Forest-Dwelling Animals in Japan.
AB - To evaluate the seed shadow generated by wild Japanese martens (Martes melampus),
we combined data on their ranging behavior from the northern foot of Mt. Fuji,
central Japan (seven males and three females) with data on gut passage time
obtained from martens in Toyama Municipal Family Park Zoo (three males and one
female). The movement distances varied, and mean distances for 0-1, 2-3, and 4-5
h intervals were 152.4, 734.7, and 1,162.4 m, respectively, with no significant
sex difference. The mean gut passage time of ingested seeds was 7.4 h (range: 0.6
51.7 h), and two-thirds were defecated within 12 h. Seeds of fleshy fruits was
frequently transported to 501-1,000 m, and 20% of ingested seeds were transported
> 1,000 m from feeding sites. We found positive correlations between body size
and home range of the animals in Japan and their seed dispersal distances. We
conclude that Japanese martens are medium-range dispersers that can transport
seeds from the source to open habitats conducive for germination and/or growth,
partly due to scent marking behaviors.
PMID- 27498795
TI - Comparative Analysis of Genome and Epigenome in Closely Related Medaka Species
Identifies Conserved Sequence Preferences for DNA Hypomethylated Domains.
AB - The genomes of vertebrates are globally methylated, but a small portion of
genomic regions are known to be hypomethylated. Although hypomethylated domains
(HMDs) have been implicated in transcriptional regulation in various ways, how a
HMD is determined in a particular genomic region remains elusive. To search for
DNA motifs essential for the formation of HMDs, we performed the genome-wide
comparative analysis of genome and DNA methylation patterns of the two medaka
inbred lines, Hd-rRII1 and HNI-II, which are derived from northern and southern
subpopulations of Japan and exhibit high levels of genetic variations (SNP, ~
3%). We successfully mapped > 70% of HMDs in both genomes and found that the
majority of those mapped HMDs are conserved between the two lines (common HMDs).
Unexpectedly, the average genetic variations are similar in the common HMD and
other genome regions. However, we identified short well-conserved motifs that are
specifically enriched in HMDs, suggesting that they may play roles in the
establishment of HMDs in the medaka genome.
PMID- 27498796
TI - De Novo Assembly of the Transcriptome of Turritopsis, a Jellyfish that Repeatedly
Rejuvenates.
AB - In most animals, aging is an irreversible process; however the species
Turritopsis sp. has been observed to undergo a rejuvenation process as many as 14
times. In the present study, we used multiplexed RNA libraries to obtain the
transcriptome from four developmental stages (St) of Turritopsis sp., including
(I) immature medusa, (II) dumpling, (III) dumpling with a short stolon, and (IV)
polyp, which had recently rejuvenated. A total of 4.02 billion paired-end reads
were assembled de novo, yielding 90,327 contigs. Our analyses revealed that
significant blast hits were recovered for 74% of the assembled contigs, and 19%
were successfully annotated with gene ontology (GO) terms. A BLAST search
demonstrated that 32% of the contigs were most similar to Hydra
vulgarissequences. Raw reads from each sample were mapped against the contigs to
find St-specific genes. This represents the first comprehensive set of de novo
transcriptome data for this species, which may provide clues toward a better
understanding of cyclical rejuvenation in multicellular animals.
PMID- 27498797
TI - Ontogeny of the Appendicular Skeleton in Melanosuchus niger (Crocodylia:
Alligatoridae).
AB - The objective of the present study was to analyze chondrogenesis and the
ossification pattern of the limbs of Melanosuchus niger in order to contribute
with possible discussions on homology and the fusion pattern of autopodial
elements and phylogeny. In the Reserva Extrativista do Lago Cunia, Rondonia,
Brazil, six nests were marked and two eggs removed from each nest at 24-hour
intervals until hatching. Embryos were cleared using KOH; bone tissue was stained
with alizarin red S and cartilage with Alcian blue. Routine staining with HE was
also performed. In the pectoral girdle, the scapula showed ossification centers
before the coracoid process. In the pelvic girdle, the ilium and the ischium were
condensed as a single cartilage, although ossification took place through two
separate centers, forming distinct elements in the adult. The pubis developed
from an independent cartilaginous center with free end, which reflects its
function in breathing. In the initial stages, the stylopodium and the zeugopodium
developed from the condensation of a Y-shaped cartilage in the limbs, and
differentiation of the primary axis and digital arch were observed. The greatest
changes were observed in the mesopodia. In their evolution, Crocodylia underwent
a vast reduction in the number of autopodial elements as a consequence of fusions
and ossification of some elements. This study shows that the chondrogenesis and
ossification sequences are dissociated. Moreover, the differences between M.
niger and other species show clear variation in the patterns for these events in
Alligatoridae.
PMID- 27498798
TI - Comparative Morphological Analysis of the Immature Stages of the Grass Blue
Butterflies Zizeeria and Zizina (Lepidoptera: Lycaenidae).
AB - The pale grass blue butterfly has been used to assess the biological effects of
the Fukushima nuclear accident. Zizeeria and Zizina are two closely related
genera of grass blue butterflies that are widely distributed in tropical to
temperate Asia, Australia, and Africa, making them suitable environmental
indicators for these areas. However, the morphological features of the immature
stages have been examined only in fragmentary fashion. Here, we reared Zizeeria
maha argia, Zizeeria maha okinawana, Zizeeria karsandra karsandra, Zizina emelina
emelina, Zizina otis labradus, and Zizina otis riukuensis using a standard
rearing method that was developed for Zizeeria maha, and comparatively identified
morphological traits to effectively classify the immature stages of species or
subspecies. Morphological information on these and other subspecies including
Zizeeria knysna knysna and Zizina otis antanossa from Africa was also collected
from literature. The subspecies were all reared successfully. The subspecies all
had dorsal nectary and tentacle organs with similar morphology. For the
subspecies of Zizeeria maha, only minor morphological differences were noted.
Similarly, the subspecies of Zizina otis shared many traits. Most importantly,
Zizeeria and Zizina differed in the shape of the sensory hairs that accompany the
dorsal nectary organ; Zizeeriahad pointed hairs, and Zizina had blunt or rounded
hairs. However, Zizina emelina exhibited several intermediate features between
these two genera. Overall, the morphological traits did not completely reflect
the conventional systematic relationships. This comparative study describes the
efficient rearing of the grass blue butterflies and provides a morphological
basis for the use of these species as environmental indicators.
PMID- 27498799
TI - Phylogenetic Relationships of Japanese Auritibicen Species (Hemiptera: Cicadidae:
Cryptotympanini) Inferred from Mitochondrial and Nuclear Gene Sequences.
AB - We investigated the phylogenetic relationships and divergence times within the
genus Auritibicen(Cicadidae: Cicadinae: Cryptotympanini), analyzing five Japanese
species (A. japonicus, A. bihamatus,A. kyushyuensis, A. esakii and A. flammatus)
and three species from East Asian mainland and Taiwan (A. atrofasciatus, A.
intermedius and A. chujoi) using mitochondrial cytochrome oxidase subunit I (COI)
and nuclear elongation factor 1-alpha (EF-1a) gene sequences. Although the EF-1a
gene tree did not resolve the relationships among these Auritibicen species, the
trees based on COI gene and the combined data set showed that Japanese taxa
comprised three distinct lineages: the individual species A. flammatus and A.
bihamatus, and the A. japonicus group, comprising A. japonicus, A. esakii and A.
kyushyuensis from Japan and A. intermedius from Korea. In A. kyushyuensis, which
comprises three populations in Kyushu, western Honshu and Shikoku, the specimens
from western Honshu and Shikoku were closely related to each other, but not to
the specimen from Kyushu; instead, they were sister to the Korean A. intermedius.
The incongruence between the gene tree and species tree necessitates further
population genetic and morphological studies to confirm the classification and
species status of the western Honshu and Shikoku populations of A. kyushyuensis,
which were originally described as two independent species. Divergence time
estimation suggested that the most recent common ancestor of Auritibicen species
studied dated back to the late Pliocene and that the species of the A. japonicus
group diverged during the mid Pleistocene. Thus, the Pleistocene climatic
fluctuation may have promoted the divergence of the Auritibicen species.
PMID- 27498800
TI - Seawater Polluted with Highly Concentrated Polycyclic Aromatic Hydrocarbons
Suppresses Osteoblastic Activity in the Scales of Goldfish, Carassius auratus.
AB - We have developed an original in vitro bioassay using teleost scale, that has
osteoclasts, osteoblasts, and bone matrix as each marker: alkaline phosphatase
(ALP) for osteoblasts and tartrate-resistant acid phosphatase (TRAP) for
osteoclasts. Using this scale in vitro bioassay, we examined the effects of
seawater polluted with highly concentrated polycyclic aromatic hydrocarbons
(PAHs) and nitro-polycyclic aromatic hydrocarbons (NPAHs) on osteoblastic and
osteoclastic activities in the present study. Polluted seawater was collected
from two sites (the Alexandria site on the Mediterranean Sea and the Suez Canal
site on the Red Sea). Total levels of PAHs in the seawater from the Alexandria
and Suez Canal sites were 1364.59 and 992.56 ng/l, respectively. We were able to
detect NPAHs in both seawater samples. Total levels of NPAHs were detected in the
seawater of the Alexandria site (12.749 ng/l) and the Suez Canal site (3.914
ng/l). Each sample of polluted seawater was added to culture medium at dilution
rates of 50, 100, and 500, and incubated with the goldfish scales for 6 hrs.
Thereafter, ALP and TRAP activities were measured. ALP activity was significantly
suppressed by both polluted seawater samples diluted at least 500 times, but TRAP
activity did not change. In addition, mRNA expressions of osteoblastic markers
(ALP, osteocalcin, and the receptor activator of the NF-kappaB ligand) decreased
significantly, as did the ALP enzyme activity. In fact, ALP activity decreased on
treatment with PAHs and NPAHs. We conclude that seawater polluted with highly
concentrated PAHs and NPAHs influences bone metabolism in teleosts.
PMID- 27498802
TI - The Behavior of Chromosomes During Parthenogenetic Oogenesis in Marmorkrebs
Procambarus fallax f. virginalis.
AB - Parthenogenetic oogenesis varies among and even within species. Based on
cytological mechanisms, it can largely be divided into apomixis (ameiotic
parthenogenesis) producing genetically identical progeny, and automixis (meiotic
parthenogenesis) producing genetically non-identical progeny. Polyploidy is
common in parthenogenetic species, although the association between
parthenogenesis and polyploidy throughout evolution is poorly understood.
Marmorkrebs, or the marbled crayfish, was first identified as a parthenogenetic
decapod and was tentatively named as Procambarus fallax f. virginalis. Previous
studies revealed that Marmorkrebs is triploid and produces genetically identical
offspring, suggesting that apomixis occurs during parthenogenetic oogenesis.
However, the behavior of chromosomes during the process of oogenesis is still not
well characterized. In this study, we observed parthenogenetic oogenesis around
the time of ovulation in P. fallax f. virginalis by histology and
immunohistochemistry. During oogenesis, the chromosomes were separated into two
groups and behaved independently from each other, and one complete division
corresponding to mitosis (the second meiosis-like division) was observed. This
suggests that parthenogenetic oogenesis in Marmorkrebs exhibits gonomery, a
phenomenon commonly found in apomictic parthenogenesis in polyploid animals.
PMID- 27498803
TI - Specimens with an Artifact Appearing as 'Three Spines' in Milnesium tardigradum
var. trispinosa Rahm, 1931 (Tardigrada).
AB - Milnesium tardigradum trispinosa Rahm, 1931 is characterized by its three spines
at the posterior end of the animal, but has never been reported since its
original description. Among mounted specimens of Milnesium sp. from Japan and M.
tardigradum s. s. from France, several cases with these 'three spines' were
observed. In these samples, the character was formed by an artifact of the
fixation process. Images of these specimens show such a striking similarity to
Milnesium tardigradum trispinosa that this taxon must be considered as having
been erroneously established as a result of misinterpretation of an artifact and
no longer valid.
PMID- 27498801
TI - A Stenohaline Medaka, Oryzias woworae, Increases Expression of Gill Na(+), K(+)
ATPase and Na(+), K(+), 2Cl(-) Cotransporter 1 to Tolerate Osmotic Stress.
AB - The present study aimed to evaluate the osmoregulatory mechanism of Daisy's
medaka, O. woworae,as well as demonstrate the major factors affecting the hypo
osmoregulatory characteristics of euryhaline and stenohaline medaka. The medaka
phylogenetic tree indicates that Daisy's medaka belongs to the celebensis species
group. The salinity tolerance of Daisy's medaka was assessed. Our findings
revealed that 200/00 (hypertonic) saltwater (SW) was lethal to Daisy's medaka.
However, 62.5% of individuals survived 100/00 (isotonic) SW with pre-acclimation
to 50/00 SW for one week. This transfer regime, "Experimental (Exp.) 100/00 SW",
was used in the following experiments. After 100/00 SW-transfer, the plasma
osmolality of Daisy's medaka significantly increased. The protein abundance and
distribution of branchial Na(+), K(+)-ATPase (NKA) and Na(+), K(+), 2Cl(-)
cotransporter 1 (NKCC1) were also examined after transfer to 100/00 SW for one
week. Gill NKA activity increased significantly after transfer to 100/00 SW.
Meanwhile, elevation of gill NKA alphaalpha-subunit protein-abundance was found
in the 100/00 SW-acclimated fish. In gill cross-sections, more and larger NKA
immunoreactive (NKA-IR) cells were observed in the Exp. 100/00 SW medaka. The
relative abundance of branchial NKCC1 protein increased significantly after
transfer to 100/00 SW. NKCC1 was distributed in the basolateral membrane of NKA
IR cells of the Exp. 100/00 SW group. Furthermore, a higher abundance of NKCC1
protein was found in the gill homogenates of the euryhaline medaka, O. dancena,
than in that of the stenohaline medaka, O. woworae.
PMID- 27498804
TI - Symbiotic Association of the Bivalve Tellimya fujitaniana (Galeommatoidea) with
the Heart Urchin Echinocardium cordatum (Spatangoida) in the Northwestern
Pacific.
AB - The bivalve Tellimya fujitaniana ( Yokoyama, 1927 ) (Galeommatoidea, Heterodonta)
was described based on a fossil shell. Until now, the biology of living animals
has not been reported. In this study, we found T. fujitaniana in a commensal
relationship with the heart urchin Echinocardium cordatum (Pennant, 1777)
(Spatangoida, Echinoidea) on the intertidal mud flats of the Seto Inland Sea,
Japan. We investigated the morphology, host associations, and reproductive
biology of this bivalve species. The elongate-ovate shell is covered by a reddish
brown ferruginous deposit. The mantle is exposed anteriorly to form a temporal
siphon, while posteriorly one pair of short tentacles is exposed. Small
individuals (shell length, SL, <= 2.1 mm) were attached to the host's body
surface; middle-sized individuals (SL 3.0-3.2 mm) were attached to or stayed
close to larger T. fujitanianathat were living freely in the host burrow. Nearly
all the large individuals (SL >= 4.8 mm) lived freely in the host burrow, behind
the urchin. This suggests that the host utilization pattern of T.
fujitanianachanges with development. Specimens with SL >= 4.8 mm had mature
gonads, mostly occupied by ova, and some individuals were brooding eggs or
veliger larvae in the gills. This species was previously assigned to Fronsella.
However, the morphology and ecology of this bivalve are very similar to those of
Tellimya ferruginosa (the type species of the genus Tellimya) in the northeastern
Atlantic Ocean. Thus, we have reassigned this species to genus Tellimya. We also
confirmed that T. fujitaniana and T. ferruginosa can be genetically distinguished
using the mitochondrial COI gene.
PMID- 27498805
TI - Morphology, Biology, and Phylogenetic Position of the Bivalve Platomysia rugata
(Heterodonta: Galeommatoidea), a Commensal with the Sipunculan Worm Sipunculus
nudus.
AB - The bivalve superfamily Galeommatoidea is characterized by its symbiotic
associations with other marine invertebrates. However, for many galeommatoideans,
the host species remains unknown. Platomysia (Galeommatoidea) is a monotypic
genus including a single species P. rugata, which is distinguished from other
galeommatoideans in having distinct and evenly spaced commarginal ribs on its
shell surface. This species was described based on a single right valve shell
collected in Nanao Bay, Japan Sea, by Habe in 1951 and has been known only from
Japanese waters. However, the biology of living animals has never been reported.
We found that this species lives in the burrows of the sipunculan worm Sipunculus
nudus in mud flats in the Seto Inland Sea, Japan. We investigated its host
association and described its shell morphology and anatomy. In addition, we
performed a phylogenetic analysis using two nuclear (18S and 28S ribosomal RNA)
genes to determine its phylogenetic position in Galeommatoidea. The result
suggests that this species belongs to the clade of commensal bivalves together
with Pseudopythina, Byssobornia, and Pergrinamor. Platomysia rugata and other two
groups of sipunculan-associated galeommatoideans were not monophyletic,
suggesting that association with sipunculans occurred at least three times in the
galeommatoid evolution.
PMID- 27498806
TI - The 'Antenna Balloon Anemone' Found in the Seto Inland Sea: New Genus and Species
of Sea Anemone, Antennapeachia setouchi (Cnidaria, Actinaria, Haloclavidae).
AB - In the present study, we report the identification of a sea anemone,
Antennapeachia setouchi, collected in the Seto Inland Sea, which represents a new
genus and new species. This new species has unusual tentacle and mesenterial
arrangements that have not been observed in other species of Haloclavidae. There
are 12 regular marginal tentacles and two 'antenna tentacles,' with the latter
always rising upward and located on the oral disk near the mouth; the species is
also characterized by its peculiar mesenterial pairs, consisting of a macrocneme
and a microcneme. Furthermore, this species shows an interesting behavior: it can
inflate its body like a balloon, lift above the seafloor, and drift with the sea
current. The presence of a single, strong siphonoglyph, physa-like aboral end,
and the lack of sphincter muscle classify this sea anemone within Haloclavidae.
It resembles Peachia species, but cannot be classified in this genus as the new
species has two pairs of mesenteries, consisting of a macrocneme and a
microcneme, and irregular antenna tentacles. Therefore, we propose a new genus
Antennapeachia to accommodate this species.
PMID- 27498807
TI - Atomistic clustering-ordering and high-strain deformation of an Al0.1CrCoFeNi
high-entropy alloy.
AB - Computational investigations of structural, chemical, and deformation behavior in
high-entropy alloys (HEAs), which possess notable mechanical strength, have been
limited due to the absence of applicable force fields. To extend investigations,
we propose a set of intermolecular potential parameters for a quinary Al-Cr-Co-Fe
Ni alloy, using the available ternary Embedded Atom Method and Lennard-Jones
potential in classical molecular-dynamics simulations. The simulation results are
validated by a comparison to first-principles Korringa-Kohn-Rostoker (KKR) -
Coherent Potential Approximation (CPA) [KKR-CPA] calculations for the HEA
structural properties (lattice constants and bulk moduli), relative stability,
pair probabilities, and high-temperature short-range ordering. The simulation
(MD)-derived properties are in quantitative agreement with KKR-CPA calculations
(first-principles) and experiments. We study AlxCrCoFeNi for Al ranging from 0 <=
x <=2 mole fractions, and find that the HEA shows large chemical clustering over
a wide temperature range for x < 0.5. At various temperatures high-strain
compression promotes atomistic rearrangements in Al0.1CrCoFeNi, resulting in a
clustering-to-ordering transition that is absent for tensile loading. Large
fluctuations under stress, and at higher temperatures, are attributed to the
thermo-plastic instability in Al0.1CrCoFeNi.
PMID- 27498808
TI - A Gene Encoding Pentatricopeptide Repeat Protein Partially Restores Fertility in
RT98-Type Cytoplasmic Male-Sterile Rice.
AB - Cytoplasmic male sterility (CMS) lines in rice, which have the cytoplasm of a
wild species and the nuclear genome of cultivated rice, are of value for the
study of genetic interactions between the mitochondrial and nuclear genomes. The
RT98-type CMS line RT98A and the fertility restorer line RT98C carry the
cytoplasm of the wild species Oryza rufipogon and the nuclear genome of the
Taichung 65 cultivar (Oryza sativa L.). Based on a classical crossing experiment,
fertility is reported to be restored gametophytically by the presence of a
tentative single gene, designated Rf98, which is derived from the cytoplasm
donor. Fine mapping of Rf98 revealed that at least two genes, which are closely
positioned, are required for complete fertility restoration in RT98A. Here, we
identified seven pentatricopeptide repeat (PPR) genes that are located within a
170 kb region as candidates for Rf98 Complementation tests revealed that the
introduction of one of these PPR genes, PPR762, resulted in the partial recovery
of fertility with a seed setting rate up to 9.3%. We conclude that PPR762 is an
essential fertility restorer gene for RT98-type CMS. The low rate of seed setting
suggested that some other genes near the Rf98 locus are also necessary for the
full recovery of seed setting.
PMID- 27498809
TI - Sustained release of piroxicam from solid lipid nanoparticle as an effective anti
inflammatory therapeutics in vivo.
AB - This study aims to investigate the solid lipid nanoparticle (SLN) as a novel
vehicle for the sustained release and transdermal delivery of piroxicam, as well
as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN
formulation was optimized and the particle size, polydispersity index, zeta
potential (ZP), encapsulation efficiency, drug release, and morphological
properties were characterized. The transdermal efficiency and mechanism of the
piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced
edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs
(Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg,
glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around
102 +/- 5.2 nm with a PDI of 0.262. The ZP is 30.21 +/- 2.05 mV. The prepared
SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no
interaction between piroxicam and the vehicle components. The presence of
polymorphic form of lipid with higher drug content in the optimized Pir-SLNs
enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with
oleic acid as enhancer can radically diffuse into both the stratum corneum and
dermal layer, as well as penetrate through the hair follicles and sebaceous
glands with significantly higher density than the other control groups. Pir-SLNs
promptly inhibited the inflammation since the 3rd hour after the treatment by
decreasing the PGE2 level. SLN was demonstrated to be a promising carrier for
encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical
preparation with great potential for anti-inflammation application.
PMID- 27498810
TI - [Medullary thyroid carcinoma in a 10-month-old child with multiple endocrine
neoplasia 2B].
AB - In infants at risk of multiple endocrine neoplasia type 2B (MEN2B) the American
Thyroid Association recommends genetic testing as soon as possible after birth
and that thyroidectomy should be performed in MEN2B RET-mutation positive
individuals as soon as possible and if possible within the first year of life. We
present a ten-month-old girl with MEN2B who had prophylactic thyroidectomy. The
surgical specimen showed medullary thyroid carcinoma. This case emphasizes the
need for early diagnosis and prophylactic thyroidectomy in MEN2B patients.
PMID- 27498811
TI - Oxidative Damage Induced by Arsenic in Mice or Rats: A Systematic Review and Meta
Analysis.
AB - In this meta-analysis, studies reporting arsenic-induced oxidative damage in
mouse models were systematically evaluated to provide a scientific understanding
of oxidative stress mechanisms associated with arsenic poisoning. Fifty-eight
relevant peer-reviewed publications were identified through exhaustive database
searching. Oxidative stress indexes assessed included superoxide dismutase (SOD),
catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), glutathione-s
transferase (GST), glutathione reductase (GR), oxidized glutathione (GSSG),
malondialdehyde (MDA), and reactive oxygen species (ROS). Our meta-analysis
showed that arsenic exposure generally suppressed measured levels of the
antioxidants, SOD, CAT, GSH, GPx, GST, and GR, but increased levels of the
oxidants, GSSG, MDA, and ROS. Arsenic valence was important and GR and MDA levels
increased to a significantly (P < 0.05) greater extent upon exposure to As3+ than
to As5+. Other factors that contributed to a greater overall oxidative effect
from arsenic exposure included intervention time, intervention method, dosage,
age of animals, and the sample source from which the indexes were estimated. Our
meta-analysis effectively summarized a wide range of studies and detected a
positive relationship between arsenic exposure and oxidative damage. These data
provide a scientific basis for the prevention and treatment of arsenic poisoning.
PMID- 27498812
TI - Scalariform-to-simple transition in vessel perforation plates triggered by
differences in climate during the evolution of Adoxaceae.
AB - BACKGROUND AND AIMS: Angiosperms with simple vessel perforations have evolved
many times independently of species having scalariform perforations, but detailed
studies to understand why these transitions in wood evolution have happened are
lacking. We focus on the striking difference in wood anatomy between two closely
related genera of Adoxaceae, Viburnum and Sambucus, and link the anatomical
divergence with climatic and physiological insights. METHODS: After performing
wood anatomical observations, we used a molecular phylogenetic framework to
estimate divergence times for 127 Adoxaceae species. The conditions under which
the genera diversified were estimated using ancestral area reconstruction and
optimization of ancestral climates, and xylem-specific conductivity measurements
were performed. KEY RESULTS: Viburnum, characterized by scalariform vessel
perforations (ancestral), diversified earlier than Sambucus, having simple
perforations (derived). Ancestral climate reconstruction analyses point to cold
temperate preference for Viburnum and warm temperate for Sambucus This is
reflected in the xylem-specific conductivity rates of the co-occurring species
investigated, showing that Viburnum lantana has rates much lower than Sambucus
nigra CONCLUSIONS: The lack of selective pressure for high conductive efficiency
during early diversification of Viburnum and the potentially adaptive value of
scalariform perforations in frost-prone cold temperate climates have led to
retention of the ancestral vessel perforation type, while higher temperatures
during early diversification of Sambucus have triggered the evolution of simple
vessel perforations, allowing more efficient long-distance water transport.
PMID- 27498814
TI - Optimal multibipolar parameters should overcome heat-sink effect.
PMID- 27498813
TI - The Impact of Carbapenem-Resistant Enterobacteriaceae Type on Clinical Outcomes
After the Recovery of This Organism From Urine of Critically Ill Patients.
PMID- 27498815
TI - Static and dynamic single leg postural control performance during dual-task
paradigms.
AB - Combining dynamic postural control assessments and cognitive tasks may give
clinicians a more accurate indication of postural control under sport-like
conditions compared to single-task assessments. We examined postural control,
cognitive and squatting performance of healthy individuals during static and
dynamic postural control assessments in single- and dual-task paradigms. Thirty
participants (female = 22, male = 8; age = 20.8 +/- 1.6 years, height = 157.9 +/-
13.0 cm, mass = 67.8 +/- 20.6 kg) completed single-leg stance and single-leg
squat assessments on a force plate individually (single-task) and concurrently
(dual-task) with two cognitive assessments, a modified Stroop test and the Brooks
Spatial Memory Test. Outcomes included centre of pressure speed, 95% confidence
ellipse, squat depth and speed and cognitive test measures (percentage of correct
answers and reaction time). Postural control performance varied between postural
control assessments and testing paradigms. Participants did not squat as deep and
squatted slower (P < 0.001) during dual-task paradigms (<=12.69 +/- 3.4 cm squat
depth, <=16.20 +/- 4.6 cm . s-1 squat speed) compared to single-task paradigms
(14.57 +/- 3.6 cm squat depth, 19.65 +/- 5.5 cm . s-1 squat speed). The
percentage of correct answers did not change across testing conditions, but
Stroop reaction time (725.81 +/- 59.2 ms; F2,58 = 7.725, P = 0.001) was slowest
during single-leg squats compared to baseline (691.64 +/- 80.1 ms; P = 0.038) and
single-task paradigms (681.33 +/- 51.5 ms; P < 0.001). Dynamic dual-task
assessments may be more challenging to the postural control system and may better
represent postural control performance during dynamic activities.
PMID- 27498816
TI - A case of Parkinson's disease following dystonia.
AB - Parkinsonism and dystonia are both disorders of the extrapyramidal motor system,
and some patients exhibit a complex of the two symptoms. Although several reports
have referred to the coexistence of these disorders as parkinsonian disorders
with dystonia, in the majority of cases, dystonia appeared after parkinsonism.
DAT-scan is useful for the early diagnosis of Parkinson's disease (PD) and other
types of parkinsonism such as dementia with Lewy bodies. This case report
describes a 67-year old woman diagnosed with axial dystonia without parkinsonism
6 years previously, which had worsened despite treatment with Botulinum toxin
injections, and hindered the patient's gait. The patient visited the hospital
because of gait disturbances and DAT-scan showed a levodopa transducer decrease
in the putamen. A few weeks later, she was re-admitted to hospital and exhibited
Parkinsonism. Levodopa improved the gait disturbances but axial dystonia was
unchanged, and a clinical diagnosis of PD was made. In the authors' opinion, this
was a rare case of parkinsonian disorders with dystonia, characterized by the
development of PD after dystonia. DAT-scan may be helpful for the diagnosis of
patients with parkinsonian disorders with dystonia.
PMID- 27498817
TI - A dural arteriovenous fistula detected during the chronic phase of cerebral
venous sinus thrombosis.
AB - A 47-year-old woman developed a headache and tinnitus in her right ear followed
by sudden-onset left hemiparesis. She had no history of trauma or thrombophilia.
Arteriography showed an occlusion of the superior sagittal sinus, and a stenosis
of the right transverse sinus. She was treated with anticoagulants; thereafter
her deficits and sinus thrombosis immediately improved. However, 7 months after
the onset, she noticed tinnitus in her left ear. Arteriography showed a dural
arteriovenous fistula extending from the left occipital artery to the left
transverse and sigmoid sinus, but no recurrence of the cerebral venous sinus
thrombosis. After manual compression of the left occipital artery was initiated,
the tinnitus and dural arteriovenous fistula did not worsen. A dural
arteriovenous fistula may be detected in patients with cerebral venous sinus
thrombosis during the chronic phase.
PMID- 27498818
TI - A case of possible paraneoplastic neurological syndrome presenting as multiple
cranial nerve palsies associated with gallbladder cancer.
AB - We report the case of a patient who had developed multiple cranial nerve palsies
in the course of possible paraneoplastic neurological syndrome (PNS) associated
with gallbladder cancer. Twelve days prior to visiting our hospital, a 69-year
old man began experiencing neurological symptoms, beginning with diplopia and
progressing to ptosis of the left palpebra and subsequent complete closure of the
eye within 8 days. Results of the initial medical examination indicated paresis
of left oculomotor (III) and abducens (VI) nerves. MRI of the brain revealed no
focal lesion that could have resulted in compression of the affected nerves,
while further examination ruled out diabetes mellitus, infection, vasculitis, and
other systemic autoimmune diseases as potential causes. Gadolinium-enhanced MRI
revealed high intensity located in the oculomotor nerves, and steroid pulse
therapy was performed based on the assumption of inflammatory diseases. Although
slight improvement was observed with respect to the left extraocular paresis,
subsequent emergence of bilateral facial nerve (VII) palsy, right abducens nerve
palsy, and right oculomotor nerve palsy occurred in succession. PET/CT performed
under suspicion of PNS, confirmed the presence of gallbladder cancer. Surgical
extirpation of the cancer occurred 3 months following the appearance of left
oculomotor paralysis, after which the patient underwent postoperative
chemotherapy. All cranial nerve palsies resolved within 2 months after the
operation, and both cancer and PNS have shown no recurrence for over 5 years.
Pathological examination of the resected tumor revealed well-differentiated
tubular adenocarcinoma showing some signs of epithelial-mesenchymal transition,
typically an indicator of a poor prognosis. Nevertheless, lymph node metastasis
did not progress beyond N2, and the cancer was completely removed by lymph node
dissection. Therefore, the presence of multiple cranial palsies in this patient
led to early detection of the asymptomatic gallbladder cancer and immediate
administration of life-saving treatment.
PMID- 27498820
TI - Anti-obesity effects of boiled tuna extract in mice with obesity induced by a
high-fat diet.
AB - The aim of this study was to examine the anti-obesity effects of boiled tuna
extract in C57BL/6N mice with obesity induced by a high-fat diet (HFD). We
determined the anti-obesity effects of boiled tuna extract (100, 200, or 400
mg/kg) on the progression of HFD-induced obesity for 10 weeks. The mice were
divided into 5 groups as follows: the normal diet (ND) group (n=10); the HFD
group (n=10); the mice fed HFD and 100 mg/kg boiled tuna extract group (n=10);
those fed a HFD and 200 mg/kg boiled tuna extract group (n=10); and those fed a
HFD and 400 mg/kg boiled tuna extract group (n=10). Changes in body weight, fat
content, serum lipid levels and lipogenic enzyme levels were measured. The
consumption of boiled tuna extract lowered epididymal tissue weight and exerted
anti-obesity effects, as reflected by the serum glucose, triglyceride (TG), total
cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
lipoprotein cholesterol (LDL-C), insulin and leptin levels. In addition, we
demonstrated changes in liver adipogenic- and lipogenic-related protein
expression by western blot analysis. Boiled tuna extract downregulated the levels
of the CCAAT/enhancer-binding protein alpha, beta and delta (C/EBPalpha, beta,
delta), and peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
adipocyte marker genes. Boiled tuna extract also attenuated adipogenic and
lipogenic gene expression, namely the levels of fatty acid synthase (FAS),
lipoprotein lipase (LPL), acetyl-CoA carboxylase (ACC), glucose transporter type
4 (Glut4) and phosphorylated adenosine monophosphate-activated protein kinase
alpha and beta (AMPKalpha, beta) in a dose-dependent manner. Moreover, the
consumption of boiled tuna extract restored the levels of superoxide dismutase
(SOD), catalase (CAT), glutamic oxaloacetic transaminase (GOT), glutamic-pyruvate
transaminase (GPT), aspartate transaminase (AST) and alanine transaminase (ALT)
to those of the control group. These results suggest that boiled tuna extract
attenuates the progression of obesity by stimulating fatty acid oxidation through
the upregulation of AMPK genes, as well as by inhibiting the synthesis of
adipogenic and lipogenic enzymes. These characteristics of boiled tuna extract
highlight its potential anti-obesity effects.
PMID- 27498819
TI - Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding
site modulate the angiogenic response.
AB - The angiogenic properties of VEGF are mediated through the binding of VEGF to its
receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous
binding region distributed on both VEGF monomers. We attempted to reproduce this
discontinuous binding site by covalently linking into a single molecular entity
two VEGF segments involved in receptor recognition. We designed and synthesized
by chemical ligation a set of peptides differing in length and flexibility of the
molecular linker joining the two VEGF segments. The biological activity of the
peptides was characterized in vitro and in vivo showing a VEGF-like activity. The
most biologically active mini-VEGF was further analyzed by NMR to determine the
atomic details of its interaction with the receptor.
PMID- 27498821
TI - Lack of association between cytotoxic T-lymphocyte antigen-4 gene polymorphisms
and lymphoid malignancy risk: evidence from a meta-analysis.
AB - Cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms have been associated with
susceptibility to lymphoid malignancies. However, results from the published
single studies are inconsistent. Therefore, the present meta-analysis was
conducted to get a more accurate estimation of the relationship between CTLA-4
gene polymorphisms and the lymphoid malignancy risk. We identified nine
independent studies accounting for 3090 subjects up to January 30, 2016. Summary
odds ratios (OR) and 95 % confidence intervals (CI) were used to evaluate the
risk of lymphoid malignancies. Overall, no significant association was found
between +49A/G (rs231775), -318C/T (rs5742909), and +6230A/G (rs3087243) CTLA-4
gene polymorphisms and lymphoid malignancies. Furthermore, ethnicity (Asian and
Caucasian) and histopathology subgroup analyses (non-Hodgkin's lymphoma) also
failed to detect an association between the studied polymorphisms and lymphoid
malignancy risk. Our study shows that common CTLA-4 gene polymorphisms may not
contribute to lymphoid malignancy susceptibility based on the current evidence.
PMID- 27498822
TI - Rod-like CuMnOx transformed from mixed oxide particles by alkaline hydrothermal
treatment as a novel catalyst for catalytic combustion of toluene.
AB - Rod-like copper manganese mixed oxides (CuMnx-NR) have been synthesized from
copper manganese mixed oxide particles by sodium hydroxide hydrothermal
treatment, and a higher BET surface area of 221 m(2) g(-1) is obtained on the
nanorod-like sample, which exhibits superior catalytic activity toward toluene
combustion at 210 degrees C due to the increase in its oxygen mobility of the
chemisorbed oxygen species as well as the increase in surface concentrations of
higher valance cations, Cu(2+), Mn(3+) and Mn(4+), in the samples.
PMID- 27498823
TI - Pedobacterpsychrotolerans sp. nov., isolated from soil.
AB - A Gram-stain-negative, non-motile, light-pink-pigmented, aerobic, rod-shaped
bacterium, designated V5RDT, was isolated from soil of Damxung county in the
Qinghai-Tibetan Plateau. Strain V5RDT grew luxuriously at 10 degrees C, at pH
9.0 and in the presence of 1 % NaCl (w/v). Phylogenetic analysis of 16S rRNA gene
sequences placed strain V5RDT in the genus Pedobacter and found that it was most
closely related to Pedobacter alluvionis DSM 19624T (97.3 %), Pedobacter
ginsenosidimutans JCM 16721T (96.84 %), Pedobacter agri DSM 19486T (96.28 %),
Pedobacter roseus JCM 13399T (96.22 %), Pedobacter sandarakinus KCTC 12559T
(95.92 %) and Pedobacter borealis DSM 19626T (95.85 %). The G+C content of the
genomic DNA of the type strain V5RDT was 37.40 mol%. DNA-DNA relatedness for the
type strain V5RDT with respect to its closest phylogenetic relative, P.
alluvionis DSM 19624T, was 62.5+/-1.7 %. The polar lipid profile of the strain
consisted of phosphatidylethanolamine, one unidentified aminolipid, one
unidentified glycolipid and two unidentified polar lipids. Menaquinone MK-7 was
the predominant respiratory quinone, and summed feature 3 (comprising C16 :
1omega7c and/or C16 : 1omega6c), iso-C15 : 0 and iso-C17 : 0 3-OH were the major
fatty acids. With respect to phenotypic characteristics, biochemical properties
and phylogenetic inference, strain V5RDT represents a novel species of the genus
Pedobacter, for which the name Pedobacter psychrotolerans sp. nov is proposed.
The type strain is V5RDT (=CGMCC 1.15644T=DSM 103236T).
PMID- 27498825
TI - Surface area-dependent second harmonic generation from silver nanorods.
AB - The nonlinear optical (NLO) properties of metallic nanoparticles strongly depend
on their size and shape. Metallic gold nanorods have already been widely
investigated, but other noble metals could also be used for nanorod fabrication
towards applications in photonics. Here we report on the synthesis and NLO
characterization of silver nanorods (AgNRs) with controllable localized surface
plasmon resonance. We have implemented an original, one-step and seedless
synthesis method, based on a spontaneous particle growth technique in the
presence of polyvinylpyrrolidone (PVP) as a capping agent. Colloidal solutions of
AgNRs with various aspect ratios (5.0; 6.3; 7.5; 8.2 and 9.7) have been obtained
and characterized using Harmonic light scattering (HLS) at 1064 nm, in order to
investigate their quadratic NLO properties. From HLS experiments, we demonstrate
that hyperpolarizability (beta) values of AgNRs display a strong dependence on
their surface area.
PMID- 27498824
TI - Evaluation of the effect of narrative writing on the stress sources of the
parents of preterm neonates admitted to the NICU.
AB - OBJECTIVE: Identification of the nurses' and families' understanding of the
stresses in the facilitates nursing interventions and increases parental
satisfaction. MATERIAL AND METHODS: The quasiexperimental study with pretest and
posttest was administered to a sample size of 70 mothers with preterm neonates
hospitalized in the NICUs of two teaching hospitals of Tehran University of
Medical during 6 months. The Parental Stressor Scale (PSS) was used. The data
were analyzed using descriptive and analytical statistical methods. RESULTS:
Evaluation of the differences in the domains of the questionnaire between the 3rd
and 10th day of admission using a multivariate analysis showed that narrative
writing had significant effects on all three domains (Roys' largest root = 2.141,
F = 47.11, p values < 0.001). The results showed that the highest stress
reduction was observed in Infant Behavior and Appearance (-11.847) followed by
Sights and Sounds of the Unit (-11.352) while the lowest stress reduction was
observed in the Parental Role Alterations (-6.149) in the intervention group,
while the control mothers experienced a stress increase in all domains.
CONCLUSION: According to the findings, narrative writing may be considered an
efficient supportive intervention to reduce the maternal stress Infant behavior
and appearance in the NICUs. However, more research is needed to justify its
implementation.
PMID- 27498826
TI - Comparison of the live-attenuated Japanese encephalitis vaccine SA14-14-2 strain
with its pre-attenuated virulent parent SA14 strain: similarities and differences
in vitro and in vivo.
AB - Japanese encephalitis virus (JEV) is the main cause of acute viral encephalitis,
primarily affecting children and young adults in the Asia-Pacific region. JEV is
a vaccine-preventable pathogen, with four types of JE vaccine licensed in
different regions of the world. To date, the most common JEV strain used in
vaccine development and production is SA14-14-2, an attenuated strain derived
from its wild-type parental strain SA14. In this study, we directly compared the
phenotypic and genotypic characteristics of SA14 and SA14-14-2 to determine the
biological and genetic properties associated with their differential virulence.
In susceptible BHK-21 cells, SA14-14-2 grew slightly more slowly and formed
smaller plaques than SA14, but unlike SA14, it showed almost no expression of the
viral protein NS1', the product of a conserved predicted RNA pseudoknot-mediated
ribosomal frameshift. In weanling ICR mice, SA14-14-2 was highly attenuated in
terms of both neuroinvasiveness and neurovirulence, with its median lethal doses
invariably over five logs higher than those of SA14 when inoculated
intramuscularly and intracerebrally. Interestingly, the neurovirulence of SA14-14
2 was dependent on mouse age, with the 1- to 7-day-old mice being highly
susceptible and the 14- to 21-day-old mice becoming resistant to intracerebral
inoculation. At the genome level, SA14-14-2 differed from SA14 by 57 nucleotides,
including one silent G-to-A substitution at position 3599 within the predicted
RNA pseudoknot for NS1' synthesis; of the 57 differences, 25 resulted in amino
acid substitutions. Our data pave the way for the development of new genetically
modified JE vaccines.
PMID- 27498827
TI - Microbacterium diaminobutyricum sp. nov., isolated from Halimione portulacoides,
which contains diaminobutyric acid in its cell wall, and emended description of
the genus Microbacterium.
AB - Three actinobacterial strains were isolated from roots of the salt-marsh plant
Halimione portulacoides collected in Ria de Aveiro, Portugal. Molecular typing
using enterobacterial repetitive intergenic consensus ERIC-PCR fingerprinting
showed the strains to be highly similar. Phylogenetic analyses based on the 16S
rRNA gene sequence and multilocus sequence analysis (MLSA) using gyrB, rpoB, recA
and ppk and 16S rRNA genes sequences showed that the strains represented a member
of the genus Microbacterium, with Microbacterium lacus DSM 18910T as the closest
phylogenetic relative. DNA-DNA hybridization between strain RZ63T and its closest
relative was below 70 %, supporting the hypothesis that it represented a distinct
genomic species. Chemotaxonomic analyses of the novel strains and their DNA G+C
contents confirmed their affiliation to the genus Microbacterium, however, the
peptidoglycan of RZ63T contained diaminobutyric acid as the diagnostic diamino
acid. In addition, physiological and fatty acid analyses revealed differences
between these strains and their phylogenetic relatives, reinforcing their status
as a distinct species. Based on the physiological, genetic and chemotaxonomic
characterisation it is proposed that the strains studied represent a novel
species of the genus Microbacterium for which the name Microbacterium
diaminobutyricum sp. nov. is proposed (type strain RZ63T=DSM 27101T=CECT 8355T).
PMID- 27498829
TI - Sphingobacterium jejuense sp. nov., with ginsenoside-converting activity,
isolated from compost.
AB - A Gram-stain-negative, strictly aerobic, non-motile, light yellow, short-rod
bacterium (designated GJ30-7T) isolated from compost, was characterized using a
polyphasic approach, in order to clarify its taxonomic position. Strain GJ30-7T
was observed to grow optimally at 30 degrees C and at pH 7.0 on R2A agar medium.
Strain Gsoil GJ30-7T possessed beta-glucosidase activity, which was responsible
for its ability to transform ginsenosides Rb1 and Rc (the two main active
components of ginseng) to ginsenoside F2. Phylogenetic analysis, based on 16S
rRNA gene sequence similarities, indicated that GJ30-7T belongs to the genus
Sphingobacterium of the family Sphingobacteriaceae and was most closely related
to Sphingobacterium yanglingense JCM 30166T (92.6 %), Sphingobacterium
psychroaquaticum KACC 18188T (92.6 %), and Sphingobacterium thermophilum KCTC
23708T (92.0 %). The DNA G+C content was 43 mol% and MK-7 was the major
isoprenoid quinone. The main polar lipids were phosphatidylethanolamine, one
unidentified phospolipid and one unknown polar lipid. In contrast to standard and
reference strains, unidentified sphingolipid was also present. The predominant
fatty acids of strain GJ30-7T were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1omega7c
and/or C16 : 1omega6c (summed feature 3) and iso-C17 : 1omega9c and/or C16 : 0 10
methyl (summed feature 9), supporting the affiliation of strain GJ30-7T to the
genus Sphingobacterium. However, strain GJ30-7T could be distinguished
genotypically and phenotypically from species of the genus Sphingobacterium with
validly published names. The novel isolate therefore represents a novel species,
for which the name Sphingobacterium jejuense sp. nov. is proposed, with the type
strain GJ30-7T (=KACC 18625T=JCM 30948T).
PMID- 27498830
TI - One-pot polyol synthesis of highly monodisperse short green silver nanorods.
AB - Green silver nanorods (Ag NRs) of a low aspect ratio (2.8) have been produced in
high yields via an optimized, simple, and robust one-pot polyol method in the
presence of tannic acid, which favors the nucleation of decahedral seeds needed
for the production of monodisperse Ag NRs. These Ag NRs were further used as
sacrificial templates to produce Au hollow nanostructures via galvanic
replacement reaction with HAuCl4 at room temperature.
PMID- 27498831
TI - Antimicrobial evaluation of selected naturally occurring oxyprenylated secondary
metabolites.
AB - This study tested the antimicrobial activity of eight selected naturally
occurring oxyprenylated secondary metabolites against Staphylococcus aureus ATCC
29213, S. epidermidis ATCC 35984, Escherichia coli ATCC 8739, Pseudomonas
aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Results showed a moderate
antimicrobial activity. The most active compounds were 3-(4-geranyloxyphenyl)-1
ethanol (4) and 3-(4-isopentenyloxyphenyl)-1-propanol (5) that were tested on
mature and in-formation biofilms of all micro-organisms, moreover the cytotoxic
activity was evaluated. Except for S. epidermidis, both compounds reduced
significantly (p < 0.05) the microbial biofilm formation at 1/2 MIC and 1/4 MIC,
in particular, compounds 4 and 5 at each concentration, inhibited E. coli biofilm
formation to a greater extent, the biofilm formation was never more than 44% in
respect to the control, moreover both compounds showed a low cytotoxic effect.
Oxyprenylated derivatives may be of great interest for the development of novel
antimicrobial therapeutic strategies and the synthesis of semi-synthetic
analogues with anti-biofilm efficacy.
PMID- 27498832
TI - Antifungal and phytotoxic activity of essential oil from root of Senecio
amplexicaulis Kunth. (Asteraceae) growing wild in high altitude-Himalayan region.
AB - This work was aimed to evaluate the essential oil from root of medicinally
important plant Senecio amplexicaulis for chemical composition, antifungal and
phytotoxic activity. The chemical composition analysed by GC/GC-MS showed the
presence of monoterpene hydrocarbons in high percentage with marker compounds as
alpha-phellandrene (48.57%), o-cymene (16.80%) and beta-ocimene (7.61%). The
essential oil exhibited significant antifungal activity against five
phytopathogenic fungi, Sclerotium rolfsii, Macrophomina phaseolina, Rhizoctonia
solani, Pythium debaryanum and Fusarium oxysporum. The oil demonstrated
remarkable phytotoxic activity in tested concentration and significant reduction
in seed germination percentage of Phalaris minor and Triticum aestivum at higher
concentrations. The roots essential oil showed high yield for one of its marker
compound (alpha-phellandrene) which makes it important natural source of this
compound.
PMID- 27498833
TI - Phenolic constituents from Wissadula periplocifolia (L.) C. Presl. and anti
inflammatory activity of 7,4'-di-O-methylisoscutellarein.
AB - This study reports the first phenolics from Wissadula genus (Malvaceae) and the
anti-inflammatory activity of 7,4'-di-O-methylisoscutellarein. Using
chromatographic methods, five phenolic compounds were isolated from aerial parts
of Wissadula periplocifolia (L.) C. Presl. The compounds were identified as 4
hydroxybenzoic acid, 3-hydroxybenzoic acid, trans-cinnamic acid, tamgermanetin
and 7,4'-di-O-methylisoscutellarein using spectroscopic methods. The flavone 7,4'
di-O-methylisoscutellarein showed anti-inflammatory activity by inhibiting
neutrophils recruitment in a mice model of pleurisy and by decreasing
significantly the production of cytokines IL-1beta and TNF-alpha.
PMID- 27498834
TI - miR-205 suppresses cell proliferation, invasion, and metastasis via regulation of
the PTEN/AKT pathway in renal cell carcinoma.
AB - The present study aimed to determine the importance of microRNA-205 (miR-205) in
the proliferation, apoptosis, invasion and metastasis of renal cell carcinoma
(RCC) cells and the underlying molecular mechanisms. Reverse transcription
polymerase chain reaction was used to quantify the expression levels of miR-205
in RCC tissue, normal tissue adjacent to carcinoma, RCC cells and normal renal
cells. It was determined that the expression levels of miR-205 in RCC tissue and
cells were reduced compared with those in normal tissue and renal cells. miR-205
mimics and the negative control were prepared and transfected into RCC cells.
Cell viability and apoptosis were investigated using methyl thiazolyl tetrazolium
assay and Annexin V-fluorescein isothiocyanate/propidium iodide staining,
respectively. Cell migration and invasion were evaluated with Transwell assays.
The protein expression levels of E2F transcription factor 1 (E2F1), B-cell
lymphoma-2 (Bcl-2), E-cadherin, vimentin, phosphatase and tensin homolog (PTEN)
and phosphorylated AKT serine/threonine kinase 1 (p-AKT) were determined with
western blot analysis. It was revealed that miR-205 promoted the apoptosis of RCC
cells and suppressed their proliferation, metastasis and invasion compared with
the negative control. The expression levels of E2F1, Bcl-2, vimentin and p-AKT
were downregulated compared with the negative control. The expression levels of E
cadherin and PTEN were upregulated in the cells transfected with miR-205 mimics
compared with the negative control group. Therefore, it was concluded that miR
205 suppressed cell proliferation, invasion, and metastasis in RCC cells via
regulation of the PTEN/AKT signaling pathway. The present study may contribute to
future miRNA-based RCC therapy.
PMID- 27498835
TI - Challenges in the Standardization of Autoantibody Testing: a Comprehensive
Review.
AB - Standardization and harmonization are complementary tools to achieve higher
testing quality in laboratory medicine. Both are of great relevance and are
strongly needed in autoimmune diagnostics, due to the impressive advance in basic
research and technological development observed in this diagnostic field in
recent years that has led to the introduction of many new tests and new
analytical methods. It is, therefore, essential that this strong innovative
thrust is translated into clinical practice in a coordinated way to avoid
confusion and the risk of potentially harmful errors for the patient. However,
while standardization of antibody assays is a very complex task, harmonization of
procedures and behaviors is a more feasible target and should necessarily include
all the phases of the total testing process-in the pre-analytical phase,
appropriateness of test requests, harmonization of autoantibody terminology, and
adoption of uniform nomenclature for laboratory tests; in the analytical phase,
harmonization of measurements, and sharing of test profiles and diagnostic
algorithms; and in the post-analytical phase, harmonization of data reporting,
and criteria for interpreting immunoserological results, especially harmonization
of units, reference intervals, decision limits, and definition and notification
of critical values. We here provide and discuss some examples of harmonization
initiatives related to anti-nuclear antibodies, TSH receptor, and anti-thyroid
peroxidase antibodies and to antibodies associated with autoimmune hepatitis and
with celiac disease. These initiatives could be the starting steps to achieve a
wider consensus and a closer interaction among stakeholders in the path of
autoimmune diagnostics harmonization to enhance clinical effectiveness and
provide greater patient safety.
PMID- 27498836
TI - Mucilaginibacter fluminis sp. nov., isolated from a freshwater river.
AB - A bacterial strain, designated TTM-2T, was isolated from a water sample taken
from the Caohu River in Taiwan and characterized using a polyphasic taxonomic
approach. Cells of strain TTM-2T were Gram-stain-negative, aerobic, poly-beta
hydroxybutyrate-accumulating, non-motile, rod-shaped and covered by large
capsules; they formed light pink colonies. Growth occurred at 15-37 degrees C
(optimum, 30 degrees C), at pH 4-8 (optimum, pH 6) and with 0-1 % (w/v) NaCl
(optimum, 0.5 %, w/v). Phylogenetic analyses, based on 16S rRNA gene sequences,
showed that strain TTM-2T belonged to the genus Mucilaginibacter. The sequence
similarities between the 16S rRNA genes of strain TTM-2T and the type strains of
other species of the genus Mucilaginibacter ranged from 93.6 to 97.4 %. The
closest relatives of strain TTM-2T were Mucilaginibactersoli R9-65T (97.4 %) and
Mucilaginibactedefluvii A5T (97.1 %). The predominant fatty acids were iso-C15 :
0 (36.9 %) and summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c; 33.7 %).
The polar lipid profile consisted of phosphatidylethanolamine and several
uncharacterized aminophospholipids and phospholipids. The major isoprenoid
quinone was MK-7. The DNA G+C content of the genomic DNA was 46.6 mol%. The DNA
DNA relatedness of strain TTM-2T with respect to species of the genus
Mucilaginibacterwith validly published names was less than 70 %. On the basis of
the phylogenetic inference and phenotypic data, strain TTM-2T should be
classified as a novel species, for which the name Mucilaginibacter fluminis sp.
nov. is proposed. The type strain is TTM-2T (=BCRC 80785T=LMG 28455T=KCTC
42274T).
PMID- 27498837
TI - Simultaneous neutron diffraction and microwave dielectric characterisation of
ammine materials - a non-destructive, non-contact characterisation tool for
determining ammonia content in solids.
AB - We have investigated ammonia adsorption in group two halides (MgI2 and CaBr2)
using custom-built apparatus that permits simultaneous neutron diffraction,
microwave dielectric characterisation and out-gas mass spectroscopy of solid
state materials during ammonia adsorption. Deuterated ammonia was flowed over the
sample and the uptake - as measured by mass flow meters, mass spectroscopy and
structure - compared with the change in dielectric constant. An excellent
correlation between ammonia content and dielectric property was observed and,
when linked to diffraction, mass flow and mass spectroscopy data, could be used
to determine the amount of ammonia present within the solid. The combination of
these techniques could also be used to differentiate physisorbed and metal
coordinated ammonia and explain subtleties in the observed structural
transformations.
PMID- 27498838
TI - All-Integrated Bifunctional Separator for Li Dendrite Detection via Novel
Solution Synthesis of a Thermostable Polyimide Separator.
AB - Safe operation is crucial for lithium (Li) batteries, and therefore, developing
separators with dendrite-detection function is of great scientific and
technological interest. However, challenges have been encountered when
integrating the function into commercial polyolefin separators. Among all polymer
candidates, polyimides (PIs) are prominent due to their good thermal/mechanical
stability and electrolyte wettability. Nevertheless, it is still a challenge to
efficiently synthesize PI separators, let alone integrate additional functions.
In this work, a novel yet facile solution synthesis was developed to fabricate a
nanoporous PI separator. Specifically, recyclable LiBr was utilized as the
template for nanopores creation while the polymer was processed at the
intermediate stage. This method proves not only to be a facile synthesis with
basic lab facility but also to have promising potential for low-cost industrial
production. The as-synthesized PI separator exhibited excellent
thermal/mechanical stability and electrolyte wettability, the latter of which
further improves the ionic conductivity and thus battery rate capability.
Notably, stable full-cell cycling for over 200 cycles with a PI separator was
further achieved. Based on this method, the fabrication of an all-integrated
PI/Cu/PI bifunctional separator for dendrite detection can be fulfilled. The as
fabricated all-integrated separators prove efficient as early alarms of Li
penetration, opening up the opportunity for safer battery design by separator
engineering.
PMID- 27498841
TI - Roles of nuclear trafficking in infection by cytoplasmic negative-strand RNA
viruses: paramyxoviruses and beyond.
AB - Genome replication and virion production by most negative-sense RNA viruses
(NSVs) occurs exclusively in the cytoplasm, but many NSV-expressed proteins
undergo active nucleocytoplasmic trafficking via signals that exploit cellular
nuclear transport pathways. Nuclear trafficking has been reported both for NSV
accessory proteins (including isoforms of the rabies virus phosphoprotein, and V,
W and C proteins of paramyxoviruses) and for structural proteins. Trafficking of
the former is thought to enable accessory functions in viral modulation of
antiviral responses including the type I IFN system, but the intranuclear roles
of structural proteins such as nucleocapsid and matrix proteins, which have
critical roles in extranuclear replication and viral assembly, are less clear.
Nevertheless, nuclear trafficking of matrix protein has been reported to be
critical for efficient production of Nipah virus and Respiratory syncytial virus,
and nuclear localization of nucleocapsid protein of several morbilliviruses has
been linked to mechanisms of immune evasion. Together, these data point to the
nucleus as a significant host interface for viral proteins during infection by
NSVs with otherwise cytoplasmic life cycles. Importantly, several lines of
evidence now suggest that nuclear trafficking of these proteins may be critical
to pathogenesis and thus could provide new targets for vaccine development and
antiviral therapies.
PMID- 27498842
TI - Assessment of the Dominance Level of the R81T Target Resistance to Two
Neonicotinoid Insecticides in Myzus persicae (Hemiptera: Aphididae).
AB - Myzus persicae (Sulzer, 1776), a major crop pest worldwide, displays insecticide
resistance to most molecules. The R81T substitution on the beta1 subunit of
nicotinic receptors of acetylcholine (nAChR) confers target site resistance to
neonicotinoids and is widespread in aphid populations colonizing peach tree
orchards in Southern Europe. But the impact of this resistance in the field, as
well as ways to optimize its management, depends largely on the dominance level
of the R81T mutation. In this study, we measured by in vitro assays the response
of R81T mutation to two neonicotinoids (imidacloprid and thiacloprid) in 23 M.
persicae clones with different resistance genotypes in order to assess the
dominance status of this allele. In this study, all homozygous clones for the
R81T mutation (genotype 81(TT)) showed a much higher level of resistance to both
active substances than other clones. The heterozygous clones 81(RT) displayed a
slightly higher level of resistance than wild homozygous, though resistance
phenotypes against both neonicotinoids in these two genotypes were overlapping. A
great variation of resistance level was found within these two latter clones'
categories. The dominance level of insecticide resistance (DLC) strongly
suggested that the mutant allele 81T is semirecessive (the wild 81R allele being
rather dominant) for both insecticide molecules under test. Mean DLC values were
0.316 for imidacloprid and 0.351 for thiacloprid. Cross-resistance was shown
between imidacloprid and thiacloprid. This partial recessivity is valuable
information to broaden the knowledge on neonicotinoid resistance, a prerequisite
for devising adapted management strategies against insecticide-resistant
populations of M. persicae.
PMID- 27498840
TI - SPARC overexpression combined with radiation retards angiogenesis by suppressing
VEGF-A via miR-410 in human neuroblastoma cells.
AB - Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and
despite aggressive therapy survival rates remain low. One of the contributing
factors for low survival rates is aggressive tumor angiogenesis, which is known
to increase due to radiation, one of the standard therapies for neuroblastoma.
Therefore, targeting tumor angiogenesis can be a viable add-on therapy for the
treatment of neuroblastomas. In the present study, we demonstrate that
overexpression of secreted protein acidic and rich in cysteine (SPARC) suppresses
radiation induced angiogenesis in SK-N-BE(2) and NB1691 neuroblastoma cells. We
observed that overexpression of SPARC in SK-N-BE(2) and NB1691 cells reduced
radiation induced angiogenesis in an in vivo mouse dorsal skin model and an ex
vivo chicken CAM (chorioallantoic-membrane) model and also reduced tumor size in
subcutaneous mouse tumor models of NB. We also observed that SPARC overexpression
reduces VEGF-A expression, in SK-N-BE(2) and NB1691 NB cells via miR-410, a VEGF
A targeting microRNA. SPARC overexpression alone or in combination with miR-410
and radiation was shown to be effective at reducing angiogenesis. Moreover,
addition of miR-410 inhibitors reversed SPARC mediated inhibition of VEGF-A in
NB1691 cells but not in SK-N-BE(2) NB cells. In conclusion, the present study
demonstrates that the overexpression of SPARC in combination with radiation
reduced tumor angiogenesis by downregulating VEGF-A via miR-410.
PMID- 27498839
TI - Local and global regulation of transcription initiation in bacteria.
AB - Gene expression in bacteria relies on promoter recognition by the DNA-dependent
RNA polymerase and subsequent transcription initiation. Bacterial cells are able
to tune their transcriptional programmes to changing environments, through
numerous mechanisms that regulate the activity of RNA polymerase, or change the
set of promoters to which the RNA polymerase can bind. In this Review, we outline
our current understanding of the different factors that direct the regulation of
transcription initiation in bacteria, whether by interacting with promoters, with
RNA polymerase or with both, and we discuss the diverse molecular mechanisms that
are used by these factors to regulate gene expression.
PMID- 27498843
TI - Approved oncology drugs lack in vivo activity against Trichuris muris despite in
vitro activity.
AB - Infections with soil-transmitted helminths (STHs) are considered among the most
persistent global health problems. The few available drugs have limitations
including low efficacy against Trichuris trichiura infections. As a starting
point toward drug repositioning, we studied a set of FDA-approved oncology drugs
for activity against Trichuris muris since targets relevant to cancer therapy
might have a function in helminth biology. Drugs were tested in vitro on the
larval and adult stage of T. muris. Compounds active in vitro were tested in the
T. muris mouse model at single oral dosages of 200-400 mg/kg. Of the 114 drugs
tested in vitro, 12 showed activity against T. muris larvae (>80 % drug effect at
50 MUM). Ten of these drugs were also active on the adult worm stage (>80 % drug
effect at 50 MUM), of which six revealed IC50 values between 1.8 and 5.0 MUM.
Except for tamoxifen citrate, all in vitro active drugs were protein kinase
inhibitors. None of the drugs tested in vivo showed efficacy, revealing worm
burden reductions of 0-24 % and worm expulsion rates of 0-7.9 %. The promising in
vitro activities of protein kinases could not be confirmed in vivo. Drug
discovery against STH should be strengthened including the definition of compound
progression criteria. Follow-up structure-activity relationship studies with
modified compounds might be considered.
PMID- 27498844
TI - The influence of high-heeled shoes on strain and tension force of the anterior
talofibular ligament and plantar fascia during balanced standing and walking.
AB - High-heeled shoes have the capability to alter the strain and tension of
ligamentous structures between the foot and ankle, which may result in ankle
instability. However, high-heeled shoes can also reduce the strain on plantar
fascia, which may be beneficial for the treatment of plantar fasciitis. In this
study, the influence of heel height on strain and tension force applied to the
anterior talofibular ligament (ATL) and plantar fascia were investigated. A three
dimensional finite element model of coupled foot-ankle-shoe complex was
constructed. Four heel heights were studied in balanced standing: 0 in. (0cm), 1
in. (2.54cm), 2 in. (5.08cm), and 3 in. (7.62cm). A walking analysis was
performed using 2-in. (5.08cm) high-heeled shoes. During balanced standing, the
tension force on the ATL increased from 14.8N to 97.0N, with a six-fold increase
in strain from 0 in. to 3 in. (0-7.62cm). The tension force and the average
strain on the plantar fascia decreased from 151.0N (strain: 0.74%) to 59.6N
(strain: 0.28%) when the heel height increased from 0 in. to 2 in. (0-5.08cm).
When heel height reached 3 in. (7.62cm), the force and average strain increased
to 278.3N (strain: 1.33%). The walking simulation showed that the fascia
stretched out while the ATL loading decreased during push off. The simulation
outcome demonstrated the influence of heel height on ATL alteration and plantar
fascia strain, which implies risks for ankle injury and suggests guidance for the
treatment of plantar fasciitis.
PMID- 27498845
TI - Brevibacterium massiliense (Roux and Raoult 2009) is a later heterotypic synonym
of Brevibacterium ravenspurgense (Mages, Frodl, Bernard and Funke 2009), using
whole-genome sequence analysis as a comparative tool.
AB - A patient strain derived from urine was found by 16S rRNA gene sequencing to be
closely related (99.6 % identity) to sequences derived from both Brevibacterium
ravenspurgense CCUG 56047T and Brevibacterium massilienseCCUG 53855T. Those
species had been described during the same 11 month period in 2008-2009. Further
characterization revealed that those isolates could not be readily distinguished
from each other biochemically, by cellular fatty acids, antimicrobial
susceptibility, MALDI-TOF MS, 16S rRNA gene sequencing or by whole-genome
sequence (WGS) analyses. By WGS comparison, these isolates had an aerage
nucleotide identity using blastn (ANIb) scores of 95.7 % or higher to each other,
DNA G+C content in the range of 62.3 mol%-62.4 mol%, with genome sizes ranging
from 2.28*106 to 2.41*106 bases. Based on these data, we propose that the name B.
massiliense is a later heterotypic synonym of B. ravenspurgense and provide an
emended description of B. ravenspurgense.
PMID- 27498847
TI - Estimating fetal age: how accurate is it really?
PMID- 27498846
TI - Physiological and Pharmacological Control of BAK, BAX, and Beyond.
AB - Cellular commitment to the mitochondrial pathway of apoptosis is accomplished
when proapoptotic B cell chronic lymphocytic leukemia/lymphoma (BCL)-2 proteins
compromise mitochondrial integrity through the process of mitochondrial outer
membrane permeabilization (MOMP). For nearly three decades, intensive efforts
focused on the identification and interactions of two key proapoptotic BCL-2
proteins: BCL-2 antagonist killer (BAK) and BCL-2-associated X (BAX). Indeed, we
now have critical insights into which BCL-2 proteins interact with BAK/BAX to
either preserve survival or initiate MOMP. In contrast, while mitochondria are
targeted by BAK/BAX, a molecular understanding of how these organelles govern
BAK/BAX function remains less clear. Here, we integrate recent mechanistic
insights of proapoptotic BCL-2 protein function in the context of mitochondrial
environment, and discuss current and potential pharmacological opportunities to
control MOMP in disease.
PMID- 27498848
TI - Wenzhouxiangella sediminis sp. nov., isolated from coastal sediment.
AB - A novel Gram-stain-negative, non-spore-forming, non-motile, facultatively
anaerobic, rod-shaped strain, designated XDB06T, was isolated from coastal
sediment of Xiaoshi Island, Weihai, China. Optimal growth occurred at 37 degrees
C, pH 7.5 and with 4.0 % (w/v) NaCl. Q-8 was the sole respiratory quinone. The
major cellular fatty acids in strain XDB06T were iso-C15 : 0 and iso-C16 : 0. The
polar lipids of strain XDB06T were diphosphatidylglycerol, phosphatidylglycerol,
phosphatidylethanolamine, two unidentified glycolipids and four unidentified
phospholipids. The genomic DNA G+C content of the strain was 65.0 mol%.
Phylogenetic analysis based on 16S rRNA gene sequences showed that strain XDB06T
clusters within the genus Wenzhouxiangella and is most closely related to
Wenzhouxiangella. marina MCCC 1K00261T, with a 16S rRNA gene sequence similarity
of 96.50 %. Based on data from the current polyphasic study, strain XDB06T
represents a novel species of the genus Wenzhouxiangella, for which the name
Wenzhouxiangella sediminis sp. nov. is proposed. The type strain is XDB06T (=KCTC
52041T=MCCC 1K02285T).
PMID- 27498849
TI - Sediminibacterium aquarii sp. nov., isolated from sediment in a fishbowl.
AB - A novel bacterial strain, designated AA5T, was isolated from sediment in a
fishbowl. Cells were Gram-stain-negative, rod-shaped and strictly aerobic,
showing gliding motility. Strain AA5T was able to grow at 15-37 degrees C, at pH
5.0-8.0 and in the absence of NaCl. 16S rRNA gene sequence analysis revealed that
strain AA5T was most closely related to species in the genus Sediminibacterium,
showing highest similarity to the type strain of S.ediminibacterium goheungense
(96.6 %). Concordantly, a phylogenetic tree based on 16S rRNA gene sequences
indicated that strain AA5T belongs to the genus Sediminibacterium. The DNA G+C
content was 44.7 mol%. The major polar lipids were phosphatidylethanolamine, four
unidentified aminolipids, two unknown aminophospholipids and four unidentified
polar lipids. The only respiratory quinone of strain AA5T was menaquinone 7 (MK
7) and the major fatty acids (>5 % of the total) were iso-C15 : 0, iso-C15 : 1 G,
iso-C16 : 0 3-OH, iso-C17 : 0 3-OH and iso-C15 : 0 3-OH. Based on data from this
polyphasic study, strain AA5T represents a novel species, for which the name
Sediminibacterium aquarii sp. nov. is proposed. The type strain is AA5T (=KACC
18509T=JCM 31013T).
PMID- 27498851
TI - Multi-observable Uncertainty Relations in Product Form of Variances.
AB - We investigate the product form uncertainty relations of variances for n (n >= 3)
quantum observables. In particular, tight uncertainty relations satisfied by
three observables has been derived, which is shown to be better than the ones
derived from the strengthened Heisenberg and the generalized Schrodinger
uncertainty relations, and some existing uncertainty relation for three spin-half
operators. Uncertainty relation of arbitrary number of observables is also
derived. As an example, the uncertainty relation satisfied by the eight Gell-Mann
matrices is presented.
PMID- 27498850
TI - Association between the Absolute Baseline Lymphocyte Count and Response to
Neoadjuvant Platinum-based Chemotherapy in Muscle-invasive Bladder Cancer.
AB - AIMS: Platinum-based neoadjuvant chemotherapy (NAC) improves overall survival in
muscle-invasive bladder cancer (MIBC). A pathological complete response (pCR) at
radical cystectomy after NAC is associated with better overall survival, but
there are no established predictive biomarkers of response to NAC in MIBC. The
aim of this study was to find laboratory variables associated with pCR following
NAC. MATERIALS AND METHODS: We carried out a retrospective review of MIBC
patients treated with NAC followed by radical cystectomy at the Sheba Medical
Center between 2005 and 2015. Overall survival was calculated using the Kaplan
Meier product-limit method and compared between patients who achieved or did not
achieve pCR using the Log-rank test. Baseline and pre-surgery laboratory values
were collected and compared between patients who subsequently achieved pCR and
those who did not using logistic regression. RESULTS: Fifty-eight patients
underwent radical cystectomy after NAC, with a median follow-up of 32 (range 4.8
111.4) months from diagnosis. Of 55 patients with documented pathological outcome
on radical cystectomy, 17 (31%) achieved pCR (complete responders). Of the 15
complete responders with follow-up data, 13 (87%) were still alive at time of
last follow-up for this study (July 2015). Patients who did not achieve pCR had a
significantly worse overall survival than complete responders (P = 0.0007). The
baseline lymphocyte count, neutrophil-lymphocyte ratio (NLR) and platelet
lymphocyte ratio (PLR) were significantly associated with response (P = 0.037, P
= 0.045, P = 0.042, respectively) on univariate analysis, whereas baseline
albumin, haemoglobin, neutrophils, platelets and the total white blood count were
not significantly associated with response. Lymphocyte counts were significantly
higher in responders than non-responders throughout three time points (P = 0.003
using a generalised linear mixed model). CONCLUSIONS: A high baseline level of
lymphocytes is associated with the achievement of pCR at radical cystectomy after
NAC, which, in turn, is associated with a significantly longer overall survival.
Our results suggest that chemosensitivity in MIBC is associated with lymphocyte
count.
PMID- 27498852
TI - Control of quorum sensing and virulence factors of Pseudomonas aeruginosa using
phenylalanine arginyl beta-naphthylamide.
AB - The spread of multidrug-resistant Pseudomonas aeruginosa isolates constitutes a
serious clinical challenge. Bacterial efflux machinery is a crucial mechanism of
resistance among P. aeruginosa. Efflux inhibitors such as phenylalanine arginyl
beta-naphthylamide (PAbetaN) promote the bacterial susceptibility to
antimicrobial agents. The pathogenesis of P. aeruginosa is coordinated via quorum
sensing (QS). This study aims to find out the impact of efflux pump inhibitor,
PAbetaN, on QS and virulence attributes in clinical isolates of P. aeruginosa. P.
aeruginosa isolates were purified from urine and wound samples, and the
antimicrobial susceptibility was carried out by disc diffusion method. The
multidrug-resistant and the virulent isolates U16, U21, W19 and W23 were
selected. PAbetaN enhanced their susceptibility to most antimicrobial agents.
PAbetaN reduced QS signalling molecules N-3-oxo-dodecanoyl-l-homoserine lactone
and N-butyryl-l-homoserine lactone without affecting bacterial viability.
Moreover, PAbetaN eliminated their virulence factors such as elastase, protease,
pyocyanin and bacterial motility. At the transcription level, PAbetaN
significantly (P<0.01) diminished the relative expression of QS cascade (lasI,
lasR, rhlI, rhlR, pqsA and pqsR) and QS regulated-type II secretory genes lasB
(elastase) and toxA (exotoxin A) compared to the control untreated isolates U16
and U21. In addition, PAbetaN eliminated the relative expression of pelA
(exopolysaccharides) in U16 and U21 isolates. Hence, P. aeruginosa-tested
isolates became hypo-virulent upon using PAbetaN. PAbetaN significantly blocked
the QS circuit and inhibited the virulence factors expressed by clinical isolates
of P. aeruginosa. PAbetaN could be a prime substrate for development of QS
inhibitors and prevention of P. aeruginosa pathogenicity.
PMID- 27498853
TI - Neurokinin-1 receptor mediated breast cancer cell migration by increased
expression of MMP-2 and MMP-14.
AB - Breast cancer (BC) is a common reason of cancer-associated death in female. To
develop novel strategy of therapeutics, it is crucial to comprehensively
understand the receptor status of BC cells on the surface and inner, because
chemical messengers can bind the receptors and promote tumorigenesis. Compared
with normal and benign samples, BC cell lines and malignant biopsies showed
higher expression of neurokinin-1 receptor (NK1). In current work, we examined
the role and mechanism of NK1 receptor signaling in BC cell migration. Human
hemokinin-1 (hHK-1) was the peripheral agonist of NK1 receptor. Our results
showed that by activating NK1 receptor, hHK-1 promoted the migration of BC cells.
Gelatin zymography and WB experiment showed that hHK-1 enhanced the levels of MMP
2 and MMP-14; inhibition of these two MMPs blocked hHK-1-induced cell migration.
We further explored the underlying mechanism. hHK-1 incuced the phosphorylation
of ERK1/2, JNK and Akt through PKC or PKA pathway. The phosphorylation of these
kinases further regulated the activation of transcriptional factor AP-1 and NF
kappaB. Inhibition of AP-1 and NF-kappaB reduced the up-regulation of MMP-2 and
MMP-14 by hHK-1. Taken together, we showed NK1 receptor was an important
regulator of human BC cell migration and a potential target for BC treatment.
PMID- 27498854
TI - Amplification-Free Detection of Circulating microRNA Biomarkers from Body Fluids
Based on Fluorogenic Oligonucleotide-Templated Reaction between Engineered
Peptide Nucleic Acid Probes: Application to Prostate Cancer Diagnosis.
AB - Highly abundant in cells, microRNAs (or miRs) play a key role as regulators of
gene expression. A proportion of them are also detectable in biofluids making
them ideal noninvasive biomarkers for pathologies in which miR levels are
aberrantly expressed, such as cancer. Peptide nucleic acids (PNAs) are engineered
uncharged oligonucleotide analogues capable of hybridizing to complementary
nucleic acids with high affinity and high specificity. Herein, novel PNA-based
fluorogenic biosensors have been designed and synthesized that target miR
biomarkers for prostate cancer (PCa). The sensing strategy is based on
oligonucleotide-templated reactions where the only miR of interest serves as a
matrix to catalyze an otherwise highly unfavorable fluorogenic reaction.
Validated in vitro using synthetic RNAs, these newly developed biosensors were
then shown to detect endogenous concentrations of miR in human blood samples
without the need for any amplification step and with minimal sample processing.
This low-cost, quantitative, and versatile sensing technology has been
technically validated using gold-standard RT-qPCR. Compared to RT-qPCR however,
this enzyme-free, isothermal blood test is amenable to incorporation into low
cost portable devices and could therefore be suitable for widespread public
screening.
PMID- 27498855
TI - MtDNA analysis reveals enriched pathogenic mutations in Tibetan highlanders.
AB - Tibetan highlanders, including Tibetans, Monpas, Lhobas, Dengs and Sherpas, are
considered highly adaptive to severe hypoxic environments. Mitochondrial DNA
(mtDNA) might be important in hypoxia adaptation given its role in coding core
subunits of oxidative phosphorylation. In this study, we employed 549 complete
highlander mtDNA sequences (including 432 random samples) to obtain a
comprehensive view of highlander mtDNA profile. In the phylogeny of a total of
36,914 sequences, we identified 21 major haplogroups representing founding events
of highlanders, most of which were coalesced in 10 kya. Through founder analysis,
we proposed a three-phase model of colonizing the plateau, i.e., pre-LGM Time (30
kya, 4.68%), post-LGM Paleolithic Time (16.8 kya, 29.31%) and Neolithic Time
(after 8 kya, 66.01% in total). We observed that pathogenic mutations occurred
far more frequently in 22 highlander-specific lineages (five lineages carrying
two pathogenic mutations and six carrying one) than in the 6,857 haplogroups of
all the 36,914 sequences (P = 4.87 * 10(-8)). Furthermore, the number of possible
pathogenic mutations carried by highlanders (in average 3.18 +/- 1.27) were
significantly higher than that in controls (2.82 +/- 1.40) (P = 1.89 * 10(-4)).
Considering that function-altering and pathogenic mutations are enriched in
highlanders, we therefore hypothesize that they may have played a role in hypoxia
adaptation.
PMID- 27498856
TI - Singapore grouper iridovirus protein VP088 is essential for viral infectivity.
AB - Viral infection is a great challenge in healthcare and agriculture. The Singapore
grouper iridovirus (SGIV) is highly infectious to numerous marine fishes and
increasingly threatens mariculture and wildlife conservation. SGIV intervention
is not available because little is known about key players and their precise
roles in SGVI infection. Here we report the precise role of VP088 as a key player
in SGIV infection. VP088 was verified as an envelope protein encoded by late gene
orf088. We show that SGIV could be neutralized with an antibody against VP088.
Depletion or deletion of VP088 significantly suppresses SGIV infection without
altering viral gene expression and host responses. By precisely quantifying the
genome copy numbers of host cells and virions, we reveal that VP088 deletion
dramatically reduces SGIV infectivity through inhibiting virus entry without
altering viral pathogenicity, genome stability and replication and progeny virus
release. These results pinpoint that VP088 is a key player in SGIV entry and
represents an ideal target for SGIV intervention.
PMID- 27498857
TI - Association between GSTM1, GSTT1, and GSTP1 variants and the risk of end stage
renal disease.
AB - INTRODUCTION: There are some evidences indicating DNA damage by oxidant and
mutant agents has an essential role in the chronic renal failure and end stage
renal disease (ESRD). To investigate the possible association of GSTs variants
with ESRD, we investigated the frequency of GST- T1, M1, and P1 genotypes, and
the level of malondialdehyde (MDA) in patients with ESRD. MATERIALS AND METHODS:
The present case-control study consisted of 136 ESRD patients treated with
maintenance hemodialysis and 137 gender- and age-matched, unrelated healthy
controls from the population of west of Iran. The GST- T1, M1, and P1 genotypes
were determined in all individuals using multiplex-PCR and PCR-RFLP. The level of
MDA was measured by high-performance liquid chromatography (HPLC). RESULTS: We
found that GSTM1 and GSTT1 null genotypes (GSTT1-/GSTM1-) increased the risk of
ESRD by 1.8 times (p < 0.001) and the increased risk of ESRD for GSTM-null (T1+
M1-) genotype was 3.04 times (p = 0.002). ESRD patients carriers the GST (GSTM1
null + GSTT1-null + GST-null) genotypes compared to GST normal genotype increased
the risk of ESRD by 3.3 (p < 0.001) times. ESRD patients carriers of GST-null,
GSTM1-null, and GSTT1-null genotypes had greater MDA concentration compared with
the same genotypes of control subjects. Our results indicated that the GST-null
allele (GSTT1-null/GSTM1-null) is a risk factor for ESRD and carriers of this
allele have high levels of MDA. CONCLUSION: Our findings indicate that oxidative
stress, impairment of the antioxidant system and abnormal lipid metabolism may
play a role in the pathogenesis and progression of ESRD and its related
complications. These data suggest that patients with ESRD are more susceptible to
vascular diseases.
PMID- 27498859
TI - Sox2 Suppresses Gastric Tumorigenesis in Mice.
AB - Sox2 expression marks gastric stem and progenitor cells, raising important
questions regarding the genes regulated by Sox2 and the role of Sox2 itself
during stomach homeostasis and disease. By using ChIP-seq analysis, we have found
that the majority of Sox2 targets in gastric epithelial cells are tissue specific
and related to functions such as endoderm development, Wnt signaling, and gastric
cancer. Unexpectedly, we found that Sox2 itself is dispensable for gastric stem
cell and epithelial self-renewal, yet Sox2(+) cells are highly susceptible to
tumorigenesis in an Apc/Wnt-driven mouse model. Moreover, Sox2 loss enhances,
rather than impairs, tumor formation in Apc-deficient gastric cells in vivo and
in vitro by inducing Tcf/Lef-dependent transcription and upregulating intestinal
metaplasia-associated genes, providing a mechanistic basis for the observed
phenotype. Together, these data identify Sox2 as a context-dependent tumor
suppressor protein that is dispensable for normal tissue regeneration but
restrains stomach adenoma formation through modulation of Wnt-responsive and
intestinal genes.
PMID- 27498858
TI - Insulin-like Signaling Promotes Glial Phagocytic Clearance of Degenerating Axons
through Regulation of Draper.
AB - Neuronal injury triggers robust responses from glial cells, including altered
gene expression and enhanced phagocytic activity to ensure prompt removal of
damaged neurons. The molecular underpinnings of glial responses to trauma remain
unclear. Here, we find that the evolutionarily conserved insulin-like signaling
(ILS) pathway promotes glial phagocytic clearance of degenerating axons in adult
Drosophila. We find that the insulin-like receptor (InR) and downstream effector
Akt1 are acutely activated in local ensheathing glia after axotomy and are
required for proper clearance of axonal debris. InR/Akt1 activity, it is also
essential for injury-induced activation of STAT92E and its transcriptional target
draper, which encodes a conserved receptor essential for glial engulfment of
degenerating axons. Increasing Draper levels in adult glia partially rescues
delayed clearance of severed axons in glial InR-inhibited flies. We propose that
ILS functions as a key post-injury communication relay to activate glial
responses, including phagocytic activity.
PMID- 27498860
TI - Interneuronal Transfer and Distal Action of Tetanus Toxin and Botulinum
Neurotoxins A and D in Central Neurons.
AB - Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used
clinically to inhibit neurotransmission, can spread within networks of neurons to
have distal effects, but this remains controversial. Moreover, it is not known
whether other members of this toxin family are transferred between neurons. Here,
we investigate the potential distal effects of BoNT/A, BoNT/D, and tetanus toxin
(TeNT), using central neurons grown in microfluidic devices. Toxins acted upon
the neurons that mediated initial entry, but all three toxins were also taken up,
via an alternative pathway, into non-acidified organelles that mediated
retrograde transport to the somato-dendritic compartment. Toxins were then
released into the media, where they entered and exerted their effects upon
upstream neurons. These findings directly demonstrate that these agents undergo
transcytosis and interneuronal transfer in an active form, resulting in long
distance effects.
PMID- 27498861
TI - MAPK-Mediated YAP Activation Controls Mechanical-Tension-Induced Pulmonary
Alveolar Regeneration.
AB - The pulmonary alveolar epithelium undergoes extensive regeneration in response to
lung injuries, including lung resection. In recent years, our understanding of
cell lineage relationships in the pulmonary alveolar epithelium has improved
significantly. However, the molecular and cellular mechanisms that regulate
pneumonectomy (PNX)-induced alveolar regeneration remain largely unknown. In this
study, we demonstrate that mechanical-tension-induced YAP activation in alveolar
stem cells plays a major role in promoting post-PNX alveolar regeneration. Our
results indicate that JNK and p38 MAPK signaling is critical for mediating actin
cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells.
Moreover, we show that Cdc42-controlled actin remodeling is required for the
activation of JNK, p38, and YAP in post-PNX lungs. Our findings together
establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for
promoting alveolar regeneration in response to mechanical tension in the lung.
PMID- 27498862
TI - Integrated Patient-Derived Models Delineate Individualized Therapeutic
Vulnerabilities of Pancreatic Cancer.
AB - Pancreatic ductal adenocarcinoma (PDAC) harbors the worst prognosis of any common
solid tumor, and multiple failed clinical trials indicate therapeutic
recalcitrance. Here, we use exome sequencing of patient tumors and find multiple
conserved genetic alterations. However, the majority of tumors exhibit no clearly
defined therapeutic target. High-throughput drug screens using patient-derived
cell lines found rare examples of sensitivity to monotherapy, with most models
requiring combination therapy. Using PDX models, we confirmed the effectiveness
and selectivity of the identified treatment responses. Out of more than 500
single and combination drug regimens tested, no single treatment was effective
for the majority of PDAC tumors, and each case had unique sensitivity profiles
that could not be predicted using genetic analyses. These data indicate a
shortcoming of reliance on genetic analysis to predict efficacy of currently
available agents against PDAC and suggest that sensitivity profiling of patient
derived models could inform personalized therapy design for PDAC.
PMID- 27498863
TI - NAMPT-Mediated NAD(+) Biosynthesis in Adipocytes Regulates Adipose Tissue
Function and Multi-organ Insulin Sensitivity in Mice.
AB - Obesity is associated with adipose tissue dysfunction and multi-organ insulin
resistance. However, the mechanisms of such obesity-associated systemic metabolic
complications are not clear. Here, we characterized mice with adipocyte-specific
deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting
NAD(+) biosynthetic enzyme known to decrease in adipose tissue of obese and aged
rodents and people. We found that adipocyte-specific Nampt knockout mice had
severe insulin resistance in adipose tissue, liver, and skeletal muscle and
adipose tissue dysfunction, manifested by increased plasma free fatty acid
concentrations and decreased plasma concentrations of a major insulin-sensitizing
adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and
PPARgamma (serine-273) and decreased gene expression of obesity-linked
phosphorylated PPARgamma targets in adipose tissue. These deleterious alterations
were normalized by administering rosiglitazone or a key NAD(+) intermediate,
nicotinamide mononucleotide (NMN). Collectively, our results provide important
mechanistic and therapeutic insights into obesity-associated systemic metabolic
derangements, particularly multi-organ insulin resistance.
PMID- 27498864
TI - Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell
Identity.
AB - Embryonic stem cells (ESCs) can self-renew or differentiate into any cell type, a
phenomenon known as pluripotency. Distinct pluripotent states, termed naive and
primed pluripotency, have been described. However, the mechanisms that control
naive-primed pluripotent transition are poorly understood. Here, we perform a
targeted screen for kinase inhibitors, which modulate the naive-primed
pluripotent transition. We find that XMD compounds, which selectively inhibit
Erk5 kinase and BET bromodomain family proteins, drive ESCs toward primed
pluripotency. Using compound selectivity engineering and CRISPR/Cas9 genome
editing, we reveal distinct functions for Erk5 and Brd4 in pluripotency
regulation. We show that Erk5 signaling maintains ESCs in the naive state and
suppresses progression toward primed pluripotency and neuroectoderm
differentiation. Additionally, we identify a specialized role for Erk5 in
defining ESC lineage selection, whereby Erk5 inhibits a cardiomyocyte-specific
differentiation program. Our data therefore reveal multiple critical functions
for Erk5 in controlling ESC identity.
PMID- 27498865
TI - TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective
Autophagy.
AB - The AIM2 inflammasome is a key cytosolic signaling complex that is activated by
double-stranded DNA, leading to the maturation of proinflammatory cytokines such
as interleukin-1beta (IL-1beta) and IL-18. Dysregulated AIM2 inflammasome
activity is associated with human inflammatory diseases and cancers, suggesting
that its activity must be tightly regulated. However, the precise molecular
mechanisms that control AIM2 levels and activity are still poorly understood.
Here, we report tripartite motif 11 (TRIM11) as a key negative regulator of the
AIM2 inflammasome. Upon DNA virus infection, TRIM11 binds to AIM2 via its PS
domain and undergoes auto-polyubiquitination at K458 to promote an association
between TRIM11 and the autophagic cargo receptor p62 to mediate AIM2 degradation
via selective autophagy. These findings identify a role for TRIMs in AIM2
inflammasome activation where TRIM11 acts as a secondary receptor to deliver AIM2
to the autophagosomes for degradation in a p62-dependent manner.
PMID- 27498866
TI - Hierarchical RNA Processing Is Required for Mitochondrial Ribosome Assembly.
AB - The regulation of mitochondrial RNA processing and its importance for ribosome
biogenesis and energy metabolism are not clear. We generated conditional knockout
mice of the endoribonuclease component of the RNase P complex, MRPP3, and report
that it is essential for life and that heart and skeletal-muscle-specific
knockout leads to severe cardiomyopathy, indicating that its activity is non
redundant. Transcriptome-wide parallel analyses of RNA ends (PARE) and RNA-seq
enabled us to identify that in vivo 5' tRNA cleavage precedes 3' tRNA processing,
and this is required for the correct biogenesis of the mitochondrial ribosomal
subunits. We identify that mitoribosomal biogenesis proceeds co-transcriptionally
because large mitoribosomal proteins can form a subcomplex on an unprocessed RNA
containing the 16S rRNA. Taken together, our data show that RNA processing links
transcription to translation via assembly of the mitoribosome.
PMID- 27498867
TI - The miR-17~92 microRNA Cluster Is a Global Regulator of Tumor Metabolism.
AB - A central hallmark of cancer cells is the reprogramming of cellular metabolism to
meet the bioenergetic and biosynthetic demands of malignant growth. Here, we
report that the miR-17~92 microRNA (miRNA) cluster is an oncogenic driver of
tumor metabolic reprogramming. Loss of miR-17~92 in Myc(+) tumor cells leads to a
global decrease in tumor cell metabolism, affecting both glycolytic and
mitochondrial metabolism, whereas increased miR-17~92 expression is sufficient to
drive increased nutrient usage by tumor cells. We mapped the metabolic control
element of miR-17~92 to the miR-17 seed family, which influences cellular
metabolism and mammalian target of rapamycin complex 1 (mTORC1) signaling through
negative regulation of the LKB1 tumor suppressor. miR-17-dependent tuning of LKB1
levels regulates both the metabolic potential of Myc(+) lymphomas and tumor
growth in vivo. Our results establish metabolic reprogramming as a central
function of the oncogenic miR-17~92 miRNA cluster that drives the progression of
MYC-dependent tumors.
PMID- 27498868
TI - MLKL and FADD Are Critical for Suppressing Progressive Lymphoproliferative
Disease and Activating the NLRP3 Inflammasome.
AB - MLKL, a key component downstream of RIPK3, is suggested to be a terminal executor
of necroptosis. Genetic studies have revealed that Ripk3 ablation rescues
embryonic lethality in Fadd- or Caspase-8-deficient mice. Given that RIPK3 has
also been implicated in non-necroptotic pathways including apoptosis and
inflammatory signaling, it remains unclear whether the lethality in Fadd(-/-)
mice is indeed caused by necropotosis. Here, we show that genetic deletion of
Mlkl rescues the developmental defect in Fadd-deficient mice and that Fadd(-/
)Mlkl(-/-) mice are viable and fertile. Mlkl(-/-)Fadd(-/-) mice display
significantly accelerated lymphoproliferative disease characterized by
lymphadenopathy and splenomegaly when compared to Ripk3(-/-)Fadd(-/-) mice. Mlkl(
/-)Fadd(-/-) bone-marrow-derived macrophages and dendritic cells have impaired
NLRP3 inflammasome activation associated with defects in ASC speck formation and
NF-kappaB-dependent NLRP3 transcription. Our findings reveal that MLKL and FADD
play critical roles in preventing lymphoproliferative disease and activating the
NLRP3 inflammasome.
PMID- 27498869
TI - A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers
Enhanced Protection to Lower Respiratory Tract Infection.
AB - The nature and anatomic location of the protective memory CD8(+) T cell subset
induced by intranasal vaccination remain poorly understood. We developed a
vaccination model to assess the anatomic location of protective memory CD8(+) T
cells and their role in lower airway infections. Memory CD8(+) T cells elicited
by local intranasal, but not systemic, vaccination with an engineered non
replicative CD8(+) T cell-targeted antigen confer enhanced protection to a lethal
respiratory viral challenge. This protection depends on a distinct CXCR3(LO)
resident memory CD8(+) T (Trm) cell population that preferentially localizes to
the pulmonary interstitium. Because they are positioned close to the mucosa,
where infection occurs, interstitial Trm cells act before inflammation can
recruit circulating memory CD8(+) T cells into the lung tissue. This results in a
local protective immune response as early as 1 day post-infection. Hence, vaccine
strategies that induce lung interstitial Trm cells may confer better protection
against respiratory pathogens.
PMID- 27498870
TI - High-Resolution Mapping of RNA Polymerases Identifies Mechanisms of Sensitivity
and Resistance to BET Inhibitors in t(8;21) AML.
AB - Bromodomain and extra-terminal domain (BET) family inhibitors offer an approach
to treating hematological malignancies. We used precision nuclear run-on
transcription sequencing (PRO-seq) to create high-resolution maps of active RNA
polymerases across the genome in t(8;21) acute myeloid leukemia (AML), as these
polymerases are exceptionally sensitive to BET inhibitors. PRO-seq identified
over 1,400 genes showing impaired release of promoter-proximal paused RNA
polymerases, including the stem cell factor receptor tyrosine kinase KIT that is
mutated in t(8;21) AML. PRO-seq also identified an enhancer 3' to KIT. Chromosome
conformation capture confirmed contacts between this enhancer and the KIT
promoter, while CRISPRi-mediated repression of this enhancer impaired cell
growth. PRO-seq also identified microRNAs, including MIR29C and MIR29B2, that
target the anti-apoptotic factor MCL1 and were repressed by BET inhibitors. MCL1
protein was upregulated, and inhibition of BET proteins sensitized t(8:21)
containing cells to MCL1 inhibition, suggesting a potential mechanism of
resistance to BET-inhibitor-induced cell death.
PMID- 27498871
TI - Direct Transcriptional Consequences of Somatic Mutation in Breast Cancer.
AB - Disordered transcriptomes of cancer encompass direct effects of somatic mutation
on transcription, coordinated secondary pathway alterations, and increased
transcriptional noise. To catalog the rules governing how somatic mutation exerts
direct transcriptional effects, we developed an exhaustive pipeline for analyzing
RNA sequencing data, which we integrated with whole genomes from 23 breast
cancers. Using X-inactivation analyses, we found that cancer cells are more
transcriptionally active than intermixed stromal cells. This is especially true
in estrogen receptor (ER)-negative tumors. Overall, 59% of substitutions were
expressed. Nonsense mutations showed lower expression levels than expected, with
patterns characteristic of nonsense-mediated decay. 14% of 4,234 rearrangements
caused transcriptional abnormalities, including exon skips, exon reusage,
fusions, and premature polyadenylation. We found productive, stable transcription
from sense-to-antisense gene fusions and gene-to-intergenic rearrangements,
suggesting that these mutation classes drive more transcriptional disruption than
previously suspected. Systematic integration of transcriptome with genome data
reveals the rules by which transcriptional machinery interprets somatic mutation.
PMID- 27498872
TI - Direct Induction and Functional Maturation of Forebrain GABAergic Neurons from
Human Pluripotent Stem Cells.
AB - Gamma-aminobutyric acid (GABA)-releasing interneurons play an important
modulatory role in the cortex and have been implicated in multiple neurological
disorders. Patient-derived interneurons could provide a foundation for studying
the pathogenesis of these diseases as well as for identifying potential
therapeutic targets. Here, we identified a set of genetic factors that could
robustly induce human pluripotent stem cells (hPSCs) into GABAergic neurons
(iGNs) with high efficiency. We demonstrated that the human iGNs express
neurochemical markers and exhibit mature electrophysiological properties within 6
8 weeks. Furthermore, in vitro, iGNs could form functional synapses with other
iGNs or with human-induced glutamatergic neurons (iENs). Upon transplantation
into immunodeficient mice, human iGNs underwent synaptic maturation and
integration into host neural circuits. Taken together, our rapid and highly
efficient single-step protocol to generate iGNs may be useful to both mechanistic
and translational studies of human interneurons.
PMID- 27498873
TI - Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs.
AB - Mutations in the 3'-5' exonuclease DIS3L2 are associated with Perlman syndrome
and hypersusceptibility to Wilms tumorigenesis. Previously, we found that Dis3l2
specifically recognizes and degrades uridylated pre-let-7 microRNA. However, the
widespread relevance of Dis3l2-mediated decay of uridylated substrates remains
unknown. Here, we applied an unbiased RNA immunoprecipitation strategy to
identify Dis3l2 targets in mouse embryonic stem cells. The disease-associated
long noncoding RNA (lncRNA) Rmrp, 7SL, as well as several other Pol III
transcribed noncoding RNAs (ncRNAs) were among the most highly enriched Dis3l2
bound RNAs. 3'-Uridylated Rmrp, 7SL, and small nuclear RNA (snRNA) species were
highly stabilized in the cytoplasm of Dis3l2-depleted cells. Deep sequencing
analysis of Rmrp 3' ends revealed extensive oligouridylation mainly on
transcripts with imprecise ends. We implicate the terminal uridylyl transferases
(TUTases) Zcchc6/11 in the uridylation of these ncRNAs, and biochemical
reconstitution assays demonstrate the sufficiency of TUTase-Dis3l2 for Rmrp
decay. This establishes Dis3l2-mediated decay (DMD) as a quality-control pathway
that eliminates aberrant ncRNAs.
PMID- 27498874
TI - Increased 4E-BP1 Expression Protects against Diet-Induced Obesity and Insulin
Resistance in Male Mice.
AB - Obesity is a major risk factor driving the global type II diabetes pandemic.
However, the molecular factors linking obesity to disease remain to be
elucidated. Gender differences are apparent in humans and are also observed in
murine models. Here, we link these differences to expression of eukaryotic
translation initiation factor 4E binding protein 1 (4E-BP1), which, upon HFD
feeding, becomes significantly reduced in the skeletal muscle and adipose tissue
of male but not female mice. Strikingly, restoring 4E-BP1 expression in male mice
protects them against HFD-induced obesity and insulin resistance. Male 4E-BP1
transgenic mice also exhibit reduced white adipose tissue accumulation
accompanied by decreased circulating levels of leptin and triglycerides.
Importantly, transgenic 4E-BP1 male mice are also protected from aging-induced
obesity and metabolic decline on a normal diet. These results demonstrate that 4E
BP1 is a gender-specific suppressor of obesity that regulates insulin sensitivity
and energy metabolism.
PMID- 27498875
TI - Distinct Roles of PKCiota/lambda and PKMzeta in the Initiation and Maintenance of
Hippocampal Long-Term Potentiation and Memory.
AB - PKMzeta has been proposed to be essential for maintenance of long-term
potentiation (LTP) and long-term memory (LTM). However, recent data from PKMzeta
knockout mice has called this role into question. Instead, the other atypical
isoform, protein kinase C iota/lambda (PKCiota/lambda), has emerged as a
potential alternative player. Therefore, the nature of the "memory molecule"
maintaining learned information remains uncertain. Here, we report knockdown (KD)
of PKCiota/lambda and PKMzeta in the dorsal hippocampus and find deficits in
early expression and late maintenance, respectively, during both LTP and
hippocampus-dependent LTM. Sequential increases in the active form of
PKCiota/lambda and PKMzeta are detected during LTP or fear conditioning.
Importantly, PKMzeta, but not PKCiota/lambda, KD disrupts previously established
LTM. Thus, PKCiota/lambda and PKMzeta have distinct functions in LTP and memory,
with PKMzeta playing a specific role in memory maintenance. This relaying pattern
may represent a precise molecular mechanism by which atypical PKCs regulate the
different stages of memory.
PMID- 27498876
TI - Binding of Macrolide Antibiotics Leads to Ribosomal Selection against Specific
Substrates Based on Their Charge and Size.
AB - Macrolide antibiotic binding to the ribosome inhibits catalysis of peptide bond
formation between specific donor and acceptor substrates. Why particular
reactions are problematic for the macrolide-bound ribosome remains unclear. Using
comprehensive mutational analysis and biochemical experiments with synthetic
substrate analogs, we find that the positive charge of these specific residues
and the length of their side chains underlie inefficient peptide bond formation
in the macrolide-bound ribosome. Even in the absence of antibiotic, peptide bond
formation between these particular donors and acceptors is rather inefficient,
suggesting that macrolides magnify a problem present for intrinsically difficult
substrates. Our findings emphasize the existence of functional interactions
between the nascent protein and the catalytic site of the ribosomal peptidyl
transferase center.
PMID- 27498877
TI - Phospho-dependent Accumulation of GABABRs at Presynaptic Terminals after NMDAR
Activation.
AB - Here, we uncover a mechanism for regulating the number of active presynaptic
GABAB receptors (GABABRs) at nerve terminals, an important determinant of
neurotransmitter release. We find that GABABRs gain access to axon terminals by
lateral diffusion in the membrane. Their relative accumulation is dependent upon
agonist activation and the presence of the two distinct sushi domains that are
found only in alternatively spliced GABABR1a subunits. Following brief activation
of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing
accumulation at presynaptic terminals in a Ca(2+)-dependent manner that involves
phosphorylation of GABABR2 subunits at Ser783. This signaling cascade indicates
how synaptically released glutamate can initiate, via a feedback mechanism,
increased levels of presynaptic GABABRs that limit further glutamate release and
excitotoxicity.
PMID- 27498878
TI - The Transcriptional Repressor Polycomb Group Factor 6, PCGF6, Negatively
Regulates Dendritic Cell Activation and Promotes Quiescence.
AB - Pro-inflammatory signals provided by the microenvironment are critical to
activate dendritic cells (DCs), components of the innate immune system that shape
both innate and adaptive immunity. However, to prevent inappropriate immune
activation, mechanisms must be in place to restrain DC activation to ensure DCs
are activated only once sufficient stimuli have been received. Here, we report
that DC activation and immunogenicity are regulated by the transcriptional
repressor Polycomb group factor 6 (PCGF6). Pcgf6 is rapidly downregulated upon
stimulation, and this downregulation is necessary to permit full DC activation.
Silencing PCGF6 expression enhanced both spontaneous and stimulated DC
activation. We show that PCGF6 associates with the H3K4me3 demethylase JARID1c,
and together, they negatively regulate H3K4me3 levels in DCs. Our results
identify two key regulators, PCGF6 and JARID1c that temper DC activation and
implicate active transcriptional silencing via histone demethylation as a
previously unappreciated mechanism for regulating DC activation and quiescence.
PMID- 27498880
TI - Nanoscale Morphology of PTB7 Based Organic Photovoltaics as a Function of
Fullerene Size.
AB - High efficiency polymer:fullerene photovoltaic device layers self-assemble with
hierarchical features from angstroms to 100's of nanometers. The feature size,
shape, composition, orientation, and order all contribute to device efficiency
and are simultaneously difficult to study due to poor contrast between carbon
based materials. This study seeks to increase device efficiency and simplify
morphology measurements by replacing the typical fullerene acceptor with
endohedral fullerene Lu3N@PC80BEH. The metal atoms give excellent scattering
contrast for electron beam and x-ray experiments. Additionally, Lu3N@PC80BEH has
a lower electron affinity than standard fullerenes, which can raise the open
circuit voltage of photovoltaic devices. Electron microscopy techniques are used
to produce a detailed account of morphology evolution in mixtures of Lu3N@PC80BEH
with the record breaking donor polymer, PTB7 and coated using solvent mixtures.
We demonstrate that common solvent additives like 1,8-diiodooctane or
chloronapthalene do not improve the morphology of endohedral fullerene devices as
expected. The poor device performance is attributed to the lack of mutual
miscibility between this particular polymer:fullerene combination and to co
crystallization of Lu3N@PC80BEH with 1,8-diiodooctane. This negative result
explains why solvent additives mixtures are not necessarily a morphology cure
all.
PMID- 27498881
TI - Monitoring cow activity and rumination time for an early detection of heat stress
in dairy cow.
AB - The aim of this study was to explore the use of cow activity and rumination time
by precision livestock farming tools as early alert for heat stress (HS)
detection. A total of 58 Italian Friesian cows were involved in this study during
summer 2015. Based on the temperature humidity index (THI), two different
conditions were compared on 16 primiparous and 11 multiparous, to be
representative of three lactation phases: early (15-84 DIM), around peak (85-154
DIM), and plateau (155-224 DIM). A separate dataset for the assessment of the
variance partition included all the cows in the herd from June 7 to July 16. The
rumination time (RT2h, min/2 h) and activity index (AI2h, bouts/2 h) were
summarized every 2-h interval. The raw data were used to calculate the following
variables: total daily RT (RTt), daytime RT (RTd), nighttime RT (RTn), total
daily AI (AIt), daytime AI (AId), and nighttime AI (AIn). Either AIt and AId
increased, whereas RTt, RTd, and RTn decreased with higher THI in all the three
phases. The highest decrease was recorded for RTd and ranged from 49 % (early) to
45 % (plateau). The contribution of the cow within lactation phase was above 60 %
of the total variance for AI traits and a share from 33.9 % (for RTt) to 54.8 %
(RTn) for RT traits. These observations must be extended to different feeding
managements and different animal genetics to assess if different thresholds could
be identified to set an early alert system for the farmer.
PMID- 27498879
TI - Metals in Alzheimer's and Parkinson's Disease: Relevance to Dementia with Lewy
Bodies.
AB - Despite being a common form of dementia, dementia with Lewy bodies is relatively
under-researched when compared with Parkinson's disease and Alzheimer's disease.
This has arisen from the fact that dementia with Lewy bodies has been
historically difficult to diagnose resulting in a lack of well-defined clinical
cohorts and post-mortem tissue available for scientific research. Dementia with
Lewy bodies shares clinical and pathological features with both Parkinson's
disease and Alzheimer's disease so it is therefore likely that it also has
similar pathogenic mechanisms leading to disease. This review will discuss the
role of biological metals in Parkinson's disease and Alzheimer's disease and
whether there are indications that metals may also be involved in dementia with
Lewy bodies.
PMID- 27498882
TI - Impact of selected personal factors on seasonal variability of recreationist
weather perceptions and preferences in Warsaw (Poland).
AB - Weather and climate are important natural resources for tourism and recreation,
although sometimes they can make outdoor leisure activities less satisfying or
even impossible. The aim of this work was to determine weather perception
seasonal variability of people staying outdoors in urban environment for tourism
and recreation, as well as to determine if personal factors influence estimation
of recreationist actual biometeorological conditions and personal expectations
towards weather elements. To investigate how human thermal sensations vary upon
meteorological conditions typical for temperate climate, weather perception field
researches were conducted in Warsaw (Poland) in all seasons. Urban
recreationists' preference for slightly warm thermal conditions, sunny, windless
and cloudless weather, were identified as well as PET values considered to be
optimal for sightseeing were defined between 27.3 and 31.7 degrees C. The
results confirmed existence of phenomena called alliesthesia, which manifested in
divergent thermal perception of comparable biometeorological conditions in
transitional seasons. The results suggest that recreationist thermal sensations
differed from other interviewees' responses and were affected not only by
physiological processes but they were also conditioned by psychological factors
(i.e. attitude, expectations). Significant impact of respondents' place of origin
and its climate on creating thermal sensations and preferences was observed. Sex
and age influence thermal preferences, whereas state of acclimatization is
related with thermal sensations to some point.
PMID- 27498884
TI - A bentonite-gold nanohybrid as a heterogeneous green catalyst for selective
oxidation of silanes.
AB - A highly efficient, environmentally benign and reusable heterogeneous bentonite
gold nanohybrid catalyst was designed and synthesized. This heterogeneous
catalyst could efficaciously catalyse the oxidation of organosilanes to silanols.
The reaction is 98.7% atom economical and the products were obtained in excellent
yield without the formation of disiloxanes as byproducts. The catalyst was also
well applicable for the gram scale preparation of silanols.
PMID- 27498883
TI - Hypoxic repression of pyruvate dehydrogenase activity is necessary for metabolic
reprogramming and growth of model tumours.
AB - Tumour cells fulfil the bioenergetic and biosynthetic needs of proliferation
using the available environmental metabolites. Metabolic adaptation to hypoxia
causes decreased mitochondrial function and increased lactate production. This
work examines the biological importance of the hypoxia-inducible inhibitory
phosphorylations on the pyruvate dehydrogenase E1alpha subunit. Pancreatic cancer
cell lines were genetically manipulated to alter the net phosphorylation of PDH
E1alpha through reduced kinase expression or enhanced phosphatase expression. The
modified cells were tested for hypoxic changes in phosphorylated E1alpha,
mitochondrial metabolism and growth as xenografted tumours. Even though there are
four PDHK genes, PDHK1 is essential for inhibitory PDH phosphorylation of E1alpha
at serine 232, is partially responsible for modification of serines 293 and 300,
and these phosphorylations are necessary for model tumour growth. In order to
determine the clinical relevance, a cohort of head and neck cancer patient
biopsies was examined for phosphorylated E1alpha and expression of PDHK1.
Patients with detectable 232 phosphorylation or expression of PDHK1 tend to have
worse clinical outcome. These data show that PDHK1 activity is unique and non
redundant in the family of PHDK enzymes and a PDHK1 specific inhibitor would
therefore have anti-cancer activity with reduced chance of side effects from
inhibition of other PDHKs.
PMID- 27498885
TI - A Density Map of the Tick-Borne Encephalitis and Lyme Borreliosis Vector Ixodes
ricinus (Acari: Ixodidae) for Germany.
AB - The castor bean tick Ixodes ricinus (L.) is the principal vector for a variety of
viral, bacterial, and protozoan pathogens causing a growing public-health issue
over the past decades. However, a national density map of I. ricinus is still
missing. Here, I. ricinus nymphs in Germany were investigated by compiling a high
resolution map depicting the mean annually accumulated nymphal density, as
observed by monthly flagging an area of 100 m2 Input data comprise ticks
collected at 69 sampling sites. The model domain covers an area of about 357,000
km2 (regional scale). Two negative binomial regression models were fitted to the
data to interpolate the tick densities to unsampled locations using bioclimatic
variables and land cover, which were selected according to their significance by
the Akaike information criterion (AIC). The default model was fitted to the
complete dataset resulting in AIC = 842. An optimized model resulted in a
significantly better value of AIC = 732. Tick densities are very low in urban
(green) areas. Maximum annual densities up to 1,000 nymphs per 100 m2 are
observed in broad-leaved forests. The tick maps were verified by leave-one-out
cross-validation. Root mean square errors of RMSE = 137 and RMSE = 126 nymphs per
100 m2 were estimated for the two models, respectively. These errors are of the
order of the interannual variation of the tick densities. The compilation of a
high-resolution density map of unfed nymphal I. ricinus for Germany provides a
novel, nationwide insight into the distribution of an important disease vector.
PMID- 27498886
TI - Golimumab for moderately to severely active ulcerative colitis.
AB - INTRODUCTION: Anti-TNF agents are the mainstay of therapy in patients with
moderate to severe ulcerative colitis (UC) not responding to 5-aminosalisylic
acid, corticosteroids, immunmodulators and for patients dependent on
corticosteroids. There is a therapeutic gap of 30%- 60% with infliximab and
adalimumab, which is required to be bridged by newer agents. The present review
summarizes the literature on the role of golimumab, a new anti TNF agent, in
ulcerative colitis. AREAS COVERED: Literature search was done on PubMed using the
search terms 'golimumab' AND 'ulcerative colitis' from inception till March 2016.
Golimumab, a fully human monoclonal antibody against TNF-alpha, was approved by
FDA for clinical use in UC in 2013. In vitro studies showed golimumab to be
better than infliximab and adalimumab in terms of affinity and neutralization of
TNF-alpha and its conformational stability. Golimumab was found to be effective
and safe in inducing and maintaining clinical remission, clinical response and
mucosal healing in patients with UC in the two registration trials. Expert
commentary: Although there is no difference in terms of efficacy between
golimumab, infliximab and adalimumab, golimumab is better than infliximab in
terms of route of administration (subcutaneous vs intravenous) and better than
adalimumab in terms of frequency of dosing (4 weeks vs 2 weeks).
PMID- 27498887
TI - Bedside teaching: an underutilized tool in medical education.
PMID- 27498888
TI - Prediction of Filamentous Sludge Bulking using a State-based Gaussian Processes
Regression Model.
AB - Activated sludge process has been widely adopted to remove pollutants in
wastewater treatment plants (WWTPs). However, stable operation of activated
sludge process is often compromised by the occurrence of filamentous bulking. The
aim of this study is to build a proper model for timely diagnosis and prediction
of filamentous sludge bulking in an activated sludge process. This study
developed a state-based Gaussian Process Regression (GPR) model to monitor the
filamentous sludge bulking related parameter, sludge volume index (SVI), in such
a way that the evolution of SVI can be predicted over multi-step ahead. This
methodology was validated with SVI data collected from one full-scale WWTP.
Online diagnosis and prediction of filamentous bulking sludge with real-time SVI
prediction was tested through a simulation study. The results showed that the
proposed methodology was capable of predicting future SVIs with good accuracy,
thus providing sufficient time for predicting and controlling filamentous sludge
bulking.
PMID- 27498890
TI - Formant transitions in the fluent speech of Farsi-speaking people who stutter.
AB - PURPOSE: Second formant (F2) transitions can be used to infer attributes of
articulatory transitions. This study compared formant transitions during fluent
speech segments of Farsi (Persian) speaking people who stutter and normally
fluent Farsi speakers. METHODS: Ten Iranian males who stutter and 10 normally
fluent Iranian males participated. Sixteen different "CVt" tokens were embedded
within the phrase "Begu CVt an". Measures included overall F2 transition
frequency extents, durations, and derived overall slopes, initial F2 transition
slopes at 30ms and 60ms, and speaking rate. RESULTS: (1) Mean overall formant
frequency extent was significantly greater in 14 of the 16 CVt tokens for the
group of stuttering speakers. (2) Stuttering speakers exhibited significantly
longer overall F2 transitions for all 16 tokens compared to the nonstuttering
speakers. (3) The overall F2 slopes were similar between the two groups. (4) The
stuttering speakers exhibited significantly greater initial F2 transition slopes
(positive or negative) for five of the 16 tokens at 30ms and six of the 16 tokens
at 60ms. (5) The stuttering group produced a slower syllable rate than the non
stuttering group. CONCLUSIONS: During perceptually fluent utterances, the
stuttering speakers had greater F2 frequency extents during transitions, took
longer to reach vowel steady state, exhibited some evidence of steeper slopes at
the beginning of transitions, had overall similar F2 formant slopes, and had
slower speaking rates compared to nonstuttering speakers. Findings support the
notion of different speech motor timing strategies in stuttering speakers.
Findings are likely to be independent of the language spoken. Educational
objectives This study compares aspects of F2 formant transitions between 10
stuttering and 10 nonstuttering speakers. Readers will be able to describe: (a)
characteristics of formant frequency as a specific acoustic feature used to infer
speech movements in stuttering and nonstuttering speakers, (b) two methods of
measuring second formant (F2) transitions: the visual criteria method and fixed
time criteria method, (c) characteristics of F2 transitions in the fluent speech
of stuttering speakers and how those characteristics appear to differ from
normally fluent speakers, and (d) possible cross-linguistic effects on acoustic
analyses of stuttering.
PMID- 27498891
TI - Delayed N2 response in Go condition in a visual Go/Nogo ERP study in children who
stutter.
AB - PURPOSE OF THE STUDY: The main aim of the study was to investigate the
attentional and inhibitory abilities and their underlying processes of children
who stutter by using behavioural measurement and event-related potentials (ERP)
in a visual Go/Nogo paradigm. METHODS: Participants were 11 children who stutter
(CWS; mean age 8.1, age range 6.3-9.5 years) and 19 typically developed children
(TDC; mean age 8.1, age range 5.8-9.6 years). They performed a visual Go/Nogo
task with simultaneous EEG recording to obtain ERP responses. RESULTS: Results
showed that CWS had longer N2 and P3 latencies in the Go condition compared to
the TDC. In contrast, the groups did not differ significantly in the Nogo
condition or behavioural measures. CONCLUSIONS: Our findings did not confirm less
efficient inhibitory control in CWS but suggest atypical attentional processing
such as stimulus evaluation and response selection. EDUCATIONAL OBJECTIVES: The
reader will be able to (a) describe recent findings on attention and inhibitory
control in children who stutter, (b) describe the measurement of attentional
processing, including inhibitory control, and (c) describe the findings on
attentional processing in children who stutter as indexed by the event-related
potentials in a visual Go/Nogo paradigm.
PMID- 27498889
TI - A Highly Polymorphic Copy Number Variant in the NSF Gene is Associated with
Cocaine Dependence.
AB - Cocaine dependence is a complex psychiatric disorder involving both genetic and
environmental factors. Several neurotransmitter systems mediate cocaine's
effects, dependence and relapse, being the components of the neurotransmitter
release machinery good candidates for the disorder. Previously, we identified a
risk haplotype for cocaine dependence in the NSF gene, encoding the protein N
Ethylmaleimide-Sensitive Factor essential for synaptic vesicle turnover. Here we
examined the possible contribution to cocaine dependence of a large copy number
variant (CNV) that encompasses part of the NSF gene. We performed a case-control
association study in a discovery sample (359 cases and 356 controls) and
identified an association between cocaine dependence and the CNV (P = 0.013),
that was confirmed in the replication sample (508 cases and 569 controls, P =
7.1e-03) and in a pooled analysis (P = 1.8e-04), with an over-representation of
low number of copies in cases. Subsequently, we studied the functional impact of
the CNV on gene expression and found that the levels of two NSF transcripts were
significantly increased in peripheral blood mononuclear cells (PBMC) along with
the number of copies of the CNV. These results, together with a previous study
from our group, support the role of NSF in the susceptibility to cocaine
dependence.
PMID- 27498892
TI - Stuttering, alcohol consumption and smoking.
AB - PURPOSE: Limited research has been published regarding the association between
stuttering and substance use. An earlier study provided no evidence for such an
association, but the authors called for further research to be conducted using a
community sample. The present study used data from a community sample to
investigate whether an association between stuttering and alcohol consumption or
regular smoking exists in late adolescence and adulthood. METHODS: Regression
analyses were carried out on data from a birth cohort study, the National Child
Development Study (NCDS), whose initial cohort included 18,558 participants who
have since been followed up until age 55. In the analyses, the main predictor
variable was parent-reported stuttering at age 16. Parental socio-economic group,
cohort member's sex and childhood behavioural problems were also included. The
outcome variables related to alcohol consumption and smoking habits at ages 16,
23, 33, 41, 46, 50 and 55. RESULTS: No significant association was found between
stuttering and alcohol consumption or stuttering and smoking at any of the ages.
It was speculated that the absence of significant associations might be due to
avoidance of social situations on the part of many of the participants who
stutter, or adoption of alternative coping strategies. CONCLUSION: Because of the
association between anxiety and substance use, individuals who stutter and are
anxious might be found to drink or smoke excessively, but as a group, people who
stutter are not more likely than those who do not to have high levels of
consumption of alcohol or nicotine.
PMID- 27498893
TI - International Phase II clinical trial of CBTPsych: A standalone Internet social
anxiety treatment for adults who stutter.
AB - PURPOSE: CBTPsych is an individualized, fully automated, standalone Internet
treatment program that requires no clinical contact or support. It is designed
specifically for those who stutter. Two preliminary trials demonstrated that it
may be efficacious for treating the social anxiety commonly associated with
stuttering. However, both trials involved pre- and post-treatment assessment at a
speech clinic. This contact may have increased compliance, commitment and
adherence with the program. The present study sought to establish the
effectiveness of CBTPsych in a large international trial with no contact of any
kind from researchers or clinicians. METHOD: Participants were 267 adults with a
reported history of stuttering who were given a maximum of 5 months access to
CBTPsych. Pre- and post-treatment functioning was assessed within the online
program with a range of psychometric measures. RESULTS: Forty-nine participants
(18.4%) completed all seven modules of CBTPsych and completed the post-treatment
online assessments. That compliance rate was far superior to similar community
trials of self-directed Internet mental health programs. Completion of the
program was associated with large, statistically and clinically significant
reductions for all measures. The reductions were similar to those obtained in
earlier trials of CBTPsych, and those obtained in trials of in-clinic CBT with an
expert clinician. CONCLUSIONS: CBTPsych is a promising individualized treatment
for social anxiety for a proportion of adults who stutter, which requires no
health care costs in terms of clinician contact or support. EDUCATIONAL
OBJECTIVES: The reader will be able to: (a) discuss the reasons for investigating
CBTPsych without any clinical contact; (b) describe the main components of the
CBTPsych treatment; (c) summarize the results of this clinical trial; (d)
describe how the results might affect clinical practice, if at all.
PMID- 27498894
TI - Phase II trial of a syllable-timed speech treatment for school-age children who
stutter.
AB - PURPOSE: A recent clinical trial (Andrews et al., 2012) showed Syllable Timed
Speech (STS) to be a potentially useful treatment agent for the reduction of
stuttering for school-age children. The present trial investigated a modified
version of this program that incorporated parent verbal contingencies. METHODS:
Participants were 22 stuttering children aged 6-11 years. Treatment involved
training the children and their parents to use STS in conversation. Parents were
also taught to use verbal contingencies in response to their child's stuttered
and stutter-free speech and to praise their child's use of STS. Outcome
assessments were conducted pre-treatment, at the completion of Stage 1 of the
program and 6 months and 12 months after Stage 1 completion. RESULTS: Outcomes
are reported for the 19 children who completed Stage 1 of the program. The group
mean percent stuttering reduction was 77% from pre-treatment to 12 months post
treatment, and 82% with the two least responsive participants removed. There was
considerable variation in response to the treatment. Eleven of the children
showed reduced avoidance of speaking situations and 18 were more satisfied with
their fluency post-treatment. However, there was some suggestion that stuttering
control was not sufficient to fully eliminate situation avoidance for the
children. CONCLUSIONS: The results of this trial are sufficiently encouraging to
warrant further clinical trials of the method.
PMID- 27498895
TI - Affinity Crystallography: A New Approach to Extracting High-Affinity Enzyme
Inhibitors from Natural Extracts.
AB - Natural products are an important source of novel drug scaffolds. The highly
variable and unpredictable timelines associated with isolating novel compounds
and elucidating their structures have led to the demise of exploring natural
product extract libraries in drug discovery programs. Here we introduce affinity
crystallography as a new methodology that significantly shortens the time of the
hit to active structure cycle in bioactive natural product discovery research.
This affinity crystallography approach is illustrated by using semipure fractions
of an actinomycetes culture extract to isolate and identify a cathepsin K
inhibitor and to compare the outcome with the traditional assay-guided
purification/structural analysis approach. The traditional approach resulted in
the identification of the known inhibitor antipain (1) and its new but lower
potency dehydration product 2, while the affinity crystallography approach led to
the identification of a new high-affinity inhibitor named lichostatinal (3). The
structure and potency of lichostatinal (3) was verified by total synthesis and
kinetic characterization. To the best of our knowledge, this is the first example
of isolating and characterizing a potent enzyme inhibitor from a partially
purified crude natural product extract using a protein crystallographic approach.
PMID- 27498897
TI - Editorial (Thematic Issue: Acute and Chronic Kidney Injury: From Basic Science to
Clinical Practice).
PMID- 27498896
TI - Widespread adaptive evolution during repeated evolutionary radiations in New
World lupins.
AB - The evolutionary processes that drive rapid species diversification are poorly
understood. In particular, it is unclear whether Darwinian adaptation or non
adaptive processes are the primary drivers of explosive species diversifications.
Here we show that repeated rapid radiations within New World lupins (Lupinus,
Leguminosae) were underpinned by a major increase in the frequency of adaptation
acting on coding and regulatory changes genome-wide. This contrasts with far less
frequent adaptation in genomes of slowly diversifying lupins and all other plant
genera analysed. Furthermore, widespread shifts in optimal gene expression
coincided with shifts to high rates of diversification and evolution of
perenniality, a putative key adaptation trait thought to have triggered the
evolutionary radiations in New World lupins. Our results reconcile long-standing
debate about the relative importance of protein-coding and regulatory evolution,
and represent the first unambiguous evidence for the rapid onset of lineage- and
genome-wide accelerated Darwinian evolution during rapid species diversification.
PMID- 27498898
TI - Acute Renal Failure - A Serious Complication in Patients After Kidney
Transplantation.
AB - Free radical-mediated injury releases proinflammatory cytokines and activates
innate immunity. It has been suggested that the early innate response and the
ischemic tissue damage play roles in the development of adaptive responses, which
may lead to acute kidney rejection. Various durations of hypothermic kidney
storage before transplantation add to ischemic tissue damage. The final stage of
ischemic injury occurs during reperfusion that develops hours or days after the
initial insult. Repair and regeneration processes occur together with cellular
apoptosis, autophagy and necrosis and a favorable outcome is expected if
regeneration prevails. Along the entire transplantation time course, there is a
great demand for novel immune and nonimmune injury biomarkers. The use of these
markers can be of great help in the monitoring of kidney injury in potential
kidney donors, where acute kidney damage can be overlooked, in predicting acute
transplant dysfunction during the early post-transplant periods, or in predicting
chronic changes in long term followup. Numerous investigations have demonstrated
that biomarkers that have the highest predictive value in acute kidney injury
include NGAL, Cystatin C, KIM-1, IL-18, and L-FABP. Most investigations show that
the ideal biomarker to fulfill all the needs in renal transplant has not been
identified yet. Although, in many animal models, new biomarkers are emerging for
predicting acute and chronic allograft damage, in human allograft analysis they
are still not routinely accepted and renal biopsy still remains the gold
standard.
PMID- 27498899
TI - Adhesion and non-linear rheology of adhesives with supramolecular crosslinking
points.
AB - Soft supramolecular materials are promising for the design of innovative and
highly tunable adhesives. These materials are composed of polymer chains
functionalized by strongly interacting moieties, sometimes called "stickers". In
order to systematically investigate the effect of the presence of associative
groups on the debonding properties of a supramolecular adhesive, a series of
supramolecular model systems has been characterized by probe-tack tests. These
model materials, composed of linear and low dispersity poly(butylacrylate) chains
functionalized in the middle by a single tri-urea sticker, are able to self
associate by six hydrogen bonds and range in molecular weight (Mn) between 5 and
85 kg mol(-1). The linear rheology and the nanostructure of the same materials
(called "PnBA3U") were the object of a previous study. At room temperature, the
association of polymers via hydrogen bonds induces the formation of rod-like
aggregates structured into bundles for Mn < 40 kg mol(-1) and the behavior of a
soft elastic material was observed (G'?G'' and G'~omega(0)). For higher Mn
materials, the filaments were randomly oriented and the polymers displayed a
crossover towards viscous behavior although terminal relaxation was not reached
in the experimental frequency window. All these materials show, however, similar
adhesive properties characterized by a cohesive mode of failure and low debonding
energies (Wadh < 40 J m(-2) for a debonding speed of 100 MUm s(-1)). The
debonding mechanisms observed during the adhesion tests have been investigated in
detail with an Image tools analysis developed by our group. The measure of the
projected area covered by cavities growing in the adhesive layer during debonding
can be used to estimate the true stress in the walls of the cavities and thus to
characterize the in situ large strain deformation of the thin layer during the
adhesion test itself. This analysis revealed in particular that the PnBA3U
materials with Mn < 40 kg mol(-1) soften very markedly at large deformation like
yield stress fluids, explaining the low adhesion energies measured for these
viscoelastic gels.
PMID- 27498900
TI - Change in Ankle-Brachial Index Over Time in a Screened Japanese Cohort - The
Okinawa Peripheral Arterial Disease Study.
AB - BACKGROUND: The temporal change in ankle-brachial index (ABI) in the general
population, especially in those aged <40 years, remains unclear. METHODS AND
RESULTS: ABIs of 23,673 individuals were measured in 1-day health checkups
between 2003 and 2010. Among them, 1,117 participants aged 28-76 years (mean 53+/
9 years) whose ABI was measured at least twice within an interval of >=4 years
(mean: 4.9 years) were selected for this study. Baseline ABI was the lowest at
age <40 years and increased with age. ABI significantly increased in participants
aged <40 and 40-49 years, but not in participants aged 50-59 and >=60 years. ABI
increased in participants with borderline-low baseline ABI (0.930). Extant evidence supports the association between obesity and adverse
health outcomes among individuals with depressive disorders. In addition, the
treatment of one condition (i.e. obesity or depressive disorders) appears to
improve the course of the other condition. It might be beneficial to check for
the other condition in patients presenting with one condition and treatment
should be administered to treat both conditions.
PMID- 27498908
TI - miR-124 inhibits proliferation and invasion of human retinoblastoma cells by
targeting STAT3.
AB - A growing body of evidence suggests that microRNA-124 (miR-124) functions as
tumor-suppressor, and involves in tumor initiation, development and metastasis in
major classes of human cancers; however, the biological role and underlying
molecular mechanism of miR-124 in retinoblastoma (RB) remain unknown. Therefore,
we investigated the biological activity and underlying molecular mechanism of miR
124 in human retinoblastoma. In the present study, our results demonstrated the
downregulation of miR-124 in RB tissues and RB cell lines compared with normal
retinal tissues. The ectopic expression of miR-124 in the RB cell lines (Y79 and
SO-RB50) suppresses cell proliferation, migration and invasion, induced cell
apoptosis in vitro. Furthermore, signal transducer and activator of transcription
3 (STAT3) was identified as a new target of miR-124, and overexpression of miR
124 decreased STAT3 expression on mRNA level and protein level in human RB cells.
We also found that STAT3 mRNA expression was upregulated and inversely correlated
with miR-124 expression in the RB tissues (r=-0.683; P<0.001). Restoration of the
expression of STAT3 rescues the effects induced by miR-124 in RB cells. The
findings of the present study suggested that miR-124 functioned as tumor
suppressor in RB, at least in part, by targeting STAT3, and that it could serve
as a potential candidate for RB therapeutics.
PMID- 27498909
TI - Asbestos concerns in Australian buildings.
PMID- 27498910
TI - Gene mutation linked to familial Barrett's oesophagus.
PMID- 27498911
TI - Delirium in patients with advanced cancer.
PMID- 27498912
TI - Are sarcomas hereditary?
PMID- 27498913
TI - Monogenic and polygenic determinants of sarcoma risk: an international genetic
study.
AB - BACKGROUND: Sarcomas are rare, phenotypically heterogeneous cancers that
disproportionately affect the young. Outside rare syndromes, the nature, extent,
and clinical significance of their genetic origins are not known. We aimed to
investigate the genetic basis for bone and soft-tissue sarcoma seen in routine
clinical practice. METHODS: In this genetic study, we included 1162 patients with
sarcoma from four cohorts (the International Sarcoma Kindred Study [ISKS], 966
probands; Project GENESIS, 48 probands; Asan Bio-Resource Center, 138 probands;
and kConFab, ten probands), who were older than 15 years at the time of consent
and had a histologically confirmed diagnosis of sarcoma, recruited from
specialist sarcoma clinics without regard to family history. Detailed clinical,
pathological, and pedigree information was collected, and cancer diagnoses in
probands and relatives were independently verified. Targeted exon sequencing
using blood (n=1114) or saliva (n=48) samples was done on 72 genes (selected due
to associations with increased cancer risk) and rare variants were stratified
into classes approximating the International Agency for Research on Cancer (IARC)
clinical classification for genetic variation. We did a case-control rare variant
burden analysis using 6545 Caucasian controls included from three cohorts (ISKS,
235 controls; LifePool, 2010 controls; and National Heart, Lung, and Blood
Institute Exome Sequencing Project [ESP], 4300 controls). FINDINGS: The median
age at cancer diagnosis in 1162 sarcoma probands was 46 years (IQR 29-58), 170
(15%) of 1162 probands had multiple primary cancers, and 155 (17%) of 911
families with informative pedigrees fitted recognisable cancer syndromes. Using a
case-control rare variant burden analysis, 638 (55%) of 1162 sarcoma probands
bore an excess of pathogenic germline variants (combined odds ratio [OR] 1.43,
95% CI 1.24-1.64, p<0.0001), with 227 known or expected pathogenic variants
occurring in 217 individuals. All classes of pathogenic variants (known,
expected, or predicted) were associated with earlier age of cancer onset. In
addition to TP53, ATM, ATR, and BRCA2, an unexpected excess of functionally
pathogenic variants was seen in ERCC2. Probands were more likely than controls to
have multiple pathogenic variants compared with the combined control cohort group
and the LifePool control cohort (OR 2.22, 95% CI 1.57-3.14, p=1.2 * 10(-6)) and
the cumulative burden of multiple variants correlated with earlier age at cancer
diagnosis (Mantel-Cox log-rank test for trend, p=0.0032). 66 of 1162 probands
carried notifiable variants following expert clinical review (those recognised to
be clinically significant to health and about which patients should be advised),
whereas 293 (25%) probands carried variants with potential therapeutic
significance. INTERPRETATION: About half of patients with sarcoma have putatively
pathogenic monogenic and polygenic variation in known and novel cancer genes,
with implications for risk management and treatment. FUNDING: Rainbows for Kate
Foundation, Johanna Sewell Research Foundation, Australian National Health and
Medical Research Council, Cancer Australia, Sarcoma UK, National Cancer
Institute, Liddy Shriver Sarcoma Initiative.
PMID- 27498914
TI - Genetic variation within GRIN2B in adolescents with alcohol use disorder may be
associated with larger left posterior cingulate cortex volume.
AB - OBJECTIVE: Brain structure differences and adolescent alcohol dependence both
show substantial heritability. However, exactly which genes are responsible for
brain volume variation in adolescents with substance abuse disorders are
currently unknown. The aim of this investigation was to determine whether genetic
variants previously implicated in psychiatric disorders are associated with
variation in brain volume in adolescents with alcohol use disorder (AUD).
METHODS: The cohort consisted of 58 adolescents with DSM-IV AUD and 58 age and
gender-matched controls of mixed ancestry ethnicity. An Illumina Infinium iSelect
custom 6000 bead chip was used to genotype 5348 single nucleotide polymorphisms
(SNPs) in 378 candidate genes. Magnetic resonance images were acquired and
volumes of global and regional structures were estimated using voxel-based
morphometry. To determine whether any of the genetic variants were associated
with brain volume, association analysis was conducted using linear regression in
Plink. RESULTS: From the exploratory analysis, the GRIN2B SNP rs219927 was
associated with brain volume in the left posterior cingulate cortex (p<0.05),
whereby having a G-allele was associated with a bigger volume. CONCLUSION: The
GRIN2B gene is involved in glutamatergic signalling and may be associated with
developmental differences in AUD in brain regions such as the posterior cingulate
cortex. Such differences may play a role in risk for AUD, and deserve more
detailed investigation.
PMID- 27498915
TI - A mysterious case of fever and renal failure in a traveler from Finland:
nephropathia epidemica.
PMID- 27498916
TI - Inhaled corticosteroids increase blood neutrophil count by decreasing the
expression of neutrophil adhesion molecules Mac-1 and L-selectin.
AB - OBJECTIVE: The objective was to investigate the effect of commonly used inhaled
corticosteroids on white blood cell count (WBC) and to examine the mechanisms
involved. METHODS: This randomized comparative study comprised 60 healthy adults.
We measured the effects of budesonide (by face mask inhalation or aerosol
inhaler), fluticasone (by inhaler), and saline inhalation (control) on WBC and
the differential leukocyte count, especially the absolute neutrophil count (ANC).
To elucidate the mechanisms involved, we measured the expression of the adhesion
neutrophil ligands Mac-1 (CD11b) and L-selectin (CD62L), and granulocyte colony
stimulating factor serum levels. RESULTS: Six hours after a single-dose
inhalation of budesonide, mean increases of 23.4% in WBC (95% confidence interval
[CI], 11.3-35.4) and 30.1% in ANC (95% CI, 7.2-53.0) were noted. The percentage
of neutrophils increased from 54.6% to 58.1% (P< .001). Inhaled fluticasone
increased WBC and ANC by 12.6% (95% CI, 1.5-23.7) and 22.7% (95% CI, 6.2-39.2),
respectively (P< .01 for both). The absolute lymphocyte and eosinophil counts did
not change significantly from baseline. The expression of Mac-1 and L-selectin
decreased by 51.0% (P< .01) and 30.9% (P= .02), respectively, following face mask
inhalation of budesonide and by 39.8% (P= .01) and 17.4% (P= .17), respectively,
following inhalation of fluticasone. No significant changes in granulocyte colony
stimulating factor levels were noted. CONCLUSIONS: Glucocorticoid inhalation
increases WBC by increasing ANC. Reduced neutrophil adhesion to the endothelial
surface, mediated by decreased adhesion molecule expression on neutrophils, is a
plausible mechanism. Physicians should be aware of the effect of inhaled
corticosteroids on WBC, as it may influence clinical decisions, especially in the
emergency department.
PMID- 27498917
TI - Hospital-level variation and predictors of admission after ED visits for atrial
fibrillation: 2006 to 2011.
AB - BACKGROUND: Outpatient management of atrial fibrillation can be a safe
alternative to inpatient admission after emergency department (ED) visits. We aim
to describe trends and predictors of hospital admission for atrial fibrillation
and determine the variation in admission among US hospitals. METHODS: We analyzed
ED visits and hospital admissions for adult patients with a principal diagnosis
of atrial fibrillation or atrial flutter in the Nationwide Emergency Department
Sample 2006 to 2011. We identified patient and hospital characteristics
associated with admission using hierarchical multivariate logistic regression. We
analyzed admission rates overall and for patients at low risk of thromboembolic
complications (CHA2DS2-VASc score 0). We compared hospital-level variance with
residual variance to estimate the intraclass correlation in models with and
without hospital characteristics. RESULTS: From 2006 to 2011, annual ED visits
for atrial fibrillation and atrial flutter increased by 30.9% and admission rates
decreased from 69.7% to 67.4% (P= .02). Admission was associated with setting
(metropolitan teaching vs nonmetropolitan, odds ratio = 1.93 [1.62-2.29]) and
region (Northeast vs West, odds ratio = 2.09 [1.67-2.60]). Among patients with 0
CHA2DS2-VASc score, the national average admission rate was 46.4%. The intraclass
correlation was 20.7% adjusting for patient characteristics and hospital
clustering, and 19.2% after additionally adjusting for hospital variables.
CONCLUSIONS: From 2006 to 2011, ED visits for atrial fibrillation in the United
States increased by almost a third, with a minimal change in ED admission rates.
One-fifth of variation in admission rates is due to hospital site and not
explained by hospital characteristics. Hospital-specific practice patterns may
identify opportunities to increase outpatient management.
PMID- 27498918
TI - Single rescuer ventilation using a bag-valve mask with internal handle: a
randomized crossover trial.
AB - OBJECTIVE: To compare tidal volume received during single rescuer ventilation
with a modified bag-valve mask (BVM) with integrated internal handle vs standard
BVM among healthy volunteers using a manikin model. METHODS: This study was a
randomized crossover trial of adult healthcare provider volunteers performing
ventilation on a manikin. We randomized participants to perform single rescuer
ventilation first using either a modified BVM with integrated internal handle or
a standard unmodified BVM. Participants were responsible for mask placement and
delivery of 10 breaths per minute for 3 minutes as guided by a metronome. After a
3-minute rest period, they performed ventilation using the alternative device.
The primary outcome measure was mean received tidal volume as measured by the
manikin (IngMar RespiTrainer model). Secondary outcomes included participant
reported device preference. RESULTS: Of 70 recruited participants, all completed
the study. Mean received tidal volume was higher using the modified BVM with
integrated internal handle vs standard BVM by 90 mL (95% confidence interval, 60
120 mL; P< .0001). There were no significant differences in mean received tidal
volume based on the order of study arm allocation. Eighty percent of participants
reported preference for the modified BVM over the standard BVM (95% confidence
interval, 70.0%-80.0%). CONCLUSIONS: The modified BVM with integrated internal
handle results in greater mean received tidal volume compared with standard BVM
during single rescuer ventilation in a manikin model. This modified BVM design
may prove a useful airway adjunct for ventilation.
PMID- 27498920
TI - Hydrophobicity effects in iron polypyridyl complex electrocatalysis within Nafion
thin-film electrodes.
AB - Four polypyridyl redox catalysts Fe(bp)3(2+), Fe(ph)3(2+), Fe(dm)3(2+), and
Fe(tm)3(2+) (with bp, ph, dm, and tm representing 2,2'-bipyridine, 1,10
phenanthroline, 4,4'-dimethyl-2,2'-bipyridine, and 3,4,7,8-tetramethyl-1,10
phenanthroline, respectively) are investigated for the electrocatalytic oxidation
of three analytes (nitrite, arsenite, and isoniazid). The poly-pyridyl iron
complex is exchanged into a Nafion film immobilized on a glassy carbon electrode,
which is then immersed in 0.1 M Na2SO4. Cyclic voltammetry is employed for the
evaluation of the mechanism and estimation of kinetic parameters. The
electrocatalytic behaviour going from low to high substrate concentration is
consistent with the Albery-Hillman cases of "LEty" switching to "LEk" (changing
from the first order in the substrate to half order in the substrate), denoting a
process that occurs in a reaction zone close to the electrode surface with
diffusion of charge (from the electrode surface into the film) and of anionic or
neutral analyte (from the Nafion-solution interface into the film). The relative
hydrophobicity of the iron polypyridyl catalyst within the film is shown to
affect both the diffusion of charge/electrons and analyte within the film with
Fe(tm)3(2+) providing the mildest catalyst. All three analytes, nitrite,
isoniazid, and arsenite, exhibit linear calibration ranges beneficial for
analytical applications in the micro-molar to the milli-molar range.
PMID- 27498919
TI - Imaging human teeth by phosphorus magnetic resonance with nuclear Overhauser
enhancement.
AB - Three-dimensional phosphorus MR images ((31)P MRI) of teeth are obtained at a
nominal resolution of 0.5 mm in less than 15 minutes using acquisition pulse
sequences sensitive to ultra-short transversal relaxation times. The images
directly reflect the spatially resolved phosphorus content of mineral tissue in
dentin and enamel; they show a lack of signal from pulp tissue and reduced signal
from de-mineralized carious lesions. We demonstrate for the first time that the
signal in (31)P MR images of mineralized tissue is enhanced by a (1)H-(31)P
nuclear Overhauser effect (NOE). Using teeth as a model for imaging mineralized
human tissue, graded differences in signal enhancement are observed that
correlate well with known mineral content. From solid-state NMR experiments we
conclude that the NOE is facilitated by spin diffusion and that the NOE
difference can be assigned to a higher water content and a different micro
structure of dentin. Thus, a novel method for imaging mineral content without
ionizing radiation is proposed. This method has potential use in the assessment
of de-mineralization states in humans, such as caries of teeth and osteoporosis
of bones.
PMID- 27498921
TI - The High-efficiency LED Driver for Visible Light Communication Applications.
AB - This paper presents a LED driver for VLC. The main purpose is to solve the low
data rate problem used to be in switching type LED driver. The GaN power device
is proposed to replace the traditional silicon power device of switching LED
driver for the purpose of increasing switching frequency of converter, thereby
increasing the bandwidth of data transmission. To achieve high efficiency, the
diode-connected GaN power transistor is utilized to replace the traditional
ultrafast recovery diode used to be in switching type LED driver. This work has
been experimentally evaluated on 350-mA output current. The results demonstrate
that it supports the data of PWM dimming level encoded in the PPM scheme for VLC
application. The experimental results also show that system's efficiency of 80.8%
can be achieved at 1-Mb/s data rate.
PMID- 27498922
TI - Combination of nadroparin with radiotherapy results in powerful synergistic
antitumor effects in lung adenocarcinoma A549 cells.
AB - Low-molecular-weight heparins (LMWHs), which are commonly used in venous
thromboprophylaxis and treatment, have recently been reported to have effects on
cancer metastasis in pre-clinical research studies. This study was planned to
define the synergistic antitumor effects of nadroparin (a kind of LMWH) combined
with radiotherapy in A549 cells. Six experimental groups were set up in our study
according to the different treatment: control group; irradiation (IR) group; low
dose of nadroparin group (LMWH50, L50); high dose of nadroparin group (LMWH100,
L100); LMWH50+IR group; LMWH100+IR group. The viability of A549 cells was
assessed by Cell Counting Kit-8 (CCK-8) assay. The apoptosis of tumor cells was
analyzed by flow cytometry (FCM) after treatment. The concentration of
transforming growth factor-beta1 (TGF-beta1) in the culture supernatants was
measured by enzyme-linked immunosorbent assay (ELISA). The migration and invasion
of the A549 cells were tested by the Transwell chamber assay. The expression of
survivin, CD147 and matrix metalloproteinase-2 (MMP-2) was analyzed by western
blotting. CCK-8 assay showed that irradiation or nadroparin alone slightly
inhibited the cell viability while the combined treatments significantly
inhibited the cell viability in a dose- and time-dependent manner. The apoptosis
rate showed greater improvement dose- and time-dependently in the groups
receiving combination therapy of nadroparin and irradiation than the control
group or the group receiving nadroparin or irradiation alone by FCM. ELISA assay
showed that the decreased TGF-beta1 secretion was found after combined treatments
with nadroparin and irradiation compared to either treatment alone. The Transwell
chamber assay showed that nadroparin not only significantly suppressed the
migration and invasion of A549 cells but also inhibited the enhanced ability of
migration and invasion induced by X-ray irradiation. Western blotting showed that
nadroparin inhibited the upregulated effects of survivin and MMP-2 expression
induced by radiation in the combined treatment groups in a dose- and time
dependent manner. Moreover, the expression level of CD147 was the lowest in the
combined treatment groups. This study identified that combination of nadroparin
and irradiation had a strong synergistic antitumor effect in a dose- and time
related manner in vitro, which was reflected in the inhibition of cell viability,
invasion and metastasis, promotion of apoptosis, inhibited secretion level of TGF
beta1 and downregulation of CD147, MMP-2 and survivin expression.
PMID- 27498923
TI - Pd-Catalyzed C-S Activation/Isocyanide Insertion/Hydrogenation Enables a
Selective Aerobic Oxidation/Cyclization.
AB - Unique imidoylation of thioorganics with isocyanides endows an unprecedented
aerobic oxidation process. Catalyzed by Pd(Ph3P)2Cl2 in the presence of Ph3SiH
under N2 then upon exposure to air, a wide range of alpha-acyl ketene
dithioacetals react with isocyanides to afford 5-hydroxy-alpha,beta-unsaturated
gamma-lactams via a C-S bond activation, isocyanide migratory insertion,
hydrogenation, selective aerobic oxidation, and intramolecular nucleophilic
addition sequence.
PMID- 27498924
TI - MicroRNA-186 suppresses cell proliferation and metastasis through targeting
MAP3K2 in non-small cell lung cancer.
AB - MicroRNAs are a class of small endogenous non-coding RNAs that play crucial roles
in the initiation and progression of human cancers. miR-186 was found decreased
in various human malignancies and function as a tumor suppressor. However, the
regulating mechanism of miR-186 in growth and metastasis of human non-small cell
lung cancer (NSCLC) is still poorly understood. We investigated the role of miR
186 in the growth and metastasis of human NSCLC. In the present study, we found
that miR-186 was significantly decreased in lung cancer tissues and cells.
Furthermore, overexpression of miR-186 suppressed lung cancer cell proliferation,
migration and invasion, and induced cell apoptosis. Moreover, we found that
confirmed mitogen-activated protein kinase kinase kinase 2 (MAP3K2) protein was
increased in lung cancer tissues and confirmed that MAP3K2 is a target gene of
miR-186. In addition, knockdown of MAP3K2 by RNA interference inhibited lung
cancer cell proliferation, migration and invasion, and promoted cell apoptosis in
vitro. Furthermore, we observed tthat the overexpression of MAP3K2 partially
reversed the inhibitory effect of miR-186 on the proliferation and metastasis of
A549 and HCC827 cell lines. Taken together, our data indicated that miR-186
regulates lung cancer growth and metastasis through suppressing MAP3K2
expression, at least partly. Therefore, miR-186-MAP3K2 may represent a new and
useful potential clinical treatment and diagnosis target for NSCLC.
PMID- 27498925
TI - Emerging roles for brain drug-metabolizing cytochrome P450 enzymes in
neuropsychiatric conditions and responses to drugs.
AB - P450s in the human brain were originally considered unlikely to contribute
significantly to the clearance of drugs and other xenobiotic chemicals, since
their overall expression was a small fraction of that found in the liver.
However, it is now recognized that P450s play substantial roles in the metabolism
of both exogenous and endogenous chemicals in the brain, but in a highly cell
type- and region-specific manner, in line with the greater functional
heterogeneity of the brain compared to the liver. Studies of brain P450
expression and the characterization of the catalytic activity of specific forms
expressed as recombinant enzymes have suggested possible roles for xenobiotic
metabolizing P450s in the brain. It is now possible to confirm these roles
through the use of intracerebroventricular administration of selective P450
inhibitors in animal models, coupled with brain sampling techniques to measure
drug concentrations in vivo, and modern neuroimaging techniques. The purpose of
this review is to discuss the evidence behind the functional importance of P450s
from the "xenobiotic-metabolizing" families, CYP1, CYP2 and CYP3 in the brain.
Approaches used to define the quantitative and qualitative significance of these
P450s in determining tissue-specific levels of xenobiotics in brain will be
considered. Finally, the possible roles of these enzymes in brain biochemistry
will be examined in light of the demonstrated activity of these enzymes in vitro
and the association of particular P450 forms with disease states.
PMID- 27498926
TI - Translocation of mineralo-organic nanoparticles from blood to urine: a new
mechanism for the formation of kidney stones?
AB - Recent studies indicate that mineralo-organic nanoparticles form in various human
body fluids, including blood and urine. These nanoparticles may form within renal
tubules and increase in size in supersaturated urine, eventually leading to the
formation of kidney stones. Here, we present observations suggesting that
mineralo-organic nanoparticles found in blood may induce kidney stone formation
via an alternative mechanism in which the particles translocate through
endothelial and renal epithelial cells to reach urine. We propose that this
alternative mechanism of kidney stone formation and the study of mineralo-organic
nanoparticles in general may provide novel strategies for the early detection and
treatment of ectopic calcifications and kidney stones.
PMID- 27498928
TI - Understanding the mechanism of LCST phase separation of mixed ionic liquids in
water by MD simulations.
AB - Recently, it has been found experimentally that two different amino acid ionic
liquids (ILs) can be mixed to show unique lowest critical solution temperature
(LCST) phase separation in water. However, little is known about the mechanism of
phase separation in these IL/water mixtures at the molecular level. In this work,
five kinds of amino acid ILs were chosen to study the mechanism of LCST-type
phase separation by molecular dynamics (MD) simulations. Toward this end, a
series of all-atom MD simulations were carried out on the ternary mixtures
consisting of two different ILs and water at different temperatures. The various
interaction energies and radial distribution functions (RDFs) were calculated and
analyzed for these mixed systems. It was found that for amino acid ILs, the -NH2
or -COOH group of one anion could have a hydrogen bonding interaction with the
COO(-) group of another anion. With the increase of temperature, this kind of
hydrogen bonding interaction between anions was strengthened and then the anion
H2O electrostatic interaction was weakened, which led to the LCST-type phase
separation of the mixed ILs in water. In addition, a series of MD simulations for
[P6668]1[Lys]n[Asp]1-n/H2O systems were also performed to study the effect of the
mixing ratio of ILs on phase separation. It was also noted that the experimental
critical composition corresponding to the lowest critical solution temperature
was well predicted from the total electrostatic interaction energies as a
function of mole fraction of [P6668][Lys] in these systems. The conclusions drawn
from this study may provide new insight into the LCST-type phase behavior of ILs
in water, and motivate further studies on practical applications.
PMID- 27498927
TI - Metastatic clear cell renal cell carcinoma: Circulating biomarkers to guide
antiangiogenic and immune therapies.
AB - BACKGROUND: The therapeutic armamentarium for metastatic renal cell carcinoma has
rapidly expanded over the past decade to include a number of anti-angiogenic
therapies and more recently, an immunotherapy. Biomarkers in the peripheral
circulation are easily accessible, can provide important prognostic value, and
have the potential to give important information about disease progression and
treatment sensitivity or response. MAIN FINDINGS: Herein, we review a variety of
circulating markers including circulating protein markers (VEGF-A, inflammatory
cytokines, and LDH), circulating nucleic acids (cell free DNA and micro RNAs),
and circulating cellular factors (circulating tumor cells, circulating
endothelial cells, and immune cell subsets). We discuss these biomarkers in the
context of their ability to provide prognostic and predictive information to anti
angiogenic and immunotherapeutic agents. PRINCIPAL CONCLUSIONS: While promising,
there is still much work to be done, and prospective evaluation of any potential
predictive biomarker for these therapies is greatly needed.
PMID- 27498929
TI - Clinical feature and pathophysiology of acute pancreatitis.
PMID- 27498930
TI - Progress of acute pancreatitis in basic study.
PMID- 27498931
TI - The current situations and issues of early management for acute pancreatitis.
PMID- 27498932
TI - Current status of ERCP pancreatitis and matters in future.
PMID- 27498933
TI - Endoscopic management of the complications after acute pancreatitis.
PMID- 27498934
TI - Chronic nonspecific multiple ulcers of the small intestine (CNSU) and chronic
enteropathy associated with SLCO2A1 (CEAS).
PMID- 27498935
TI - Efficacy of a diagnostic and therapeutic algorithm for Clostridium difficile
infection.
AB - In July 2012, metronidazole was approved for the treatment of Clostridium
difficile infection (CDI). To clarify the selection criteria for the drug in
terms of CDI severity, we established a diagnostic and therapeutic algorithm with
reference to the SHEA-IDSA Clinical Practice Guidelines. We compared patients
whose treatments were guided by the algorithm (29 cases, October 2012-September
2013) with patients treated prior to the development of the algorithm (37 cases,
October 2011-September 2012). All cases treated with reference to the algorithm
were diagnosed using enzyme immunoassay of C. difficile toxins A and B and
glutamate dehydrogenase;an appropriate drug was prescribed in 93.1% of the cases.
We found no significant between-group differences in the cure, recurrence, or
complication rates. However, drug costs in cases wherein treatments were guided
by the algorithm were markedly reduced. We have, thus, shown that algorithm
guided treatment is efficacious and cost-effective.
PMID- 27498936
TI - A case of large cell neuroendocrine carcinoma of the stomach with multiple liver
metastases.
AB - A 79-year-old man was admitted to our hospital to determine the cause of his
melena. He underwent esophagogastric endoscopy and computed tomography, revealing
a submucosal tumor on the anterior wall of the gastric antrum with multiple liver
metastases. Endoscopic biopsy revealed a large cell neuroendocrine cell
carcinoma. A subtotal gastrostomy was performed to prevent pyloric stenosis and
anemia caused by tumor hemorrhage. Previous studies on gastric neuroendocrine
carcinoma reported poor prognosis. Large- and small-cell types of gastric
neuroendocrine carcinomas were differentiated for the first time in the 14th
edition of the Japanese Classification of Gastric Carcinoma. It is expected that
the number of reports of gastric neuroendocrine carcinomas classified as either
the large-cell or small-cell type will increase. It is necessary to collect
information on more cases to improve prognosis and to establish appropriate
treatment guidelines.
PMID- 27498937
TI - A case report on metastatic pancreatic tumor from pulmonary adenocarcinoma that
difficult to differentiate from primary pancreatic ductal carcinoma.
AB - A woman was admitted to our department for lung adenocarcinoma and she was
treated with left upper lobectomy. The carcinoembryonic antigen level had
increased. Enhanced computed tomography showed a hypovascular tumor in the
pancreatic tail and in the extension of the distal main pancreatic duct.
Endoscopic ultrasonography (EUS) clearly showed a low echoic lesion, and
histological examination revealed adenocarcinoma. On immunostaining, the lesion
was diagnosed as metastatic adenocarcinoma of the lungs. The patient was treated
with chemotherapy for lung cancer and survived for 4 years after diagnosis.
Differentiating a metastatic lesion to the pancreas from pancreatic ductal
adenocarcinoma is very important. Accurate diagnosis enables administration of
appropriate treatment. In this case, EUS was especially useful for assessing the
tumor in the pancreas. When patients with a history of extra-pancreatic cancer
present with a pancreatic lesion, pancreatic metastases should be considered,
regardless of the time elapsed since occurrence of the primary cancer. EUS-fine
needle aspiration (FNA) with histological examination is the best method for
definitive diagnosis of pancreatic disease in this group of patients. This
approach has very high sensitivity and accuracy for the diagnosis of pancreatic
metastases.
PMID- 27498938
TI - Autopsy of anaplastic carcinoma of the pancreas producing granulocyte colony
stimulating factor.
AB - A 50-year-old man presented to a nearby hospital with high fever and anorexia. An
abdominal tumor was detected, and he was referred to our hospital. A pancreatic
tumor was detected by computed tomography and abdominal ultrasonography. He had
high fever, leukocytosis, and high serum granulocyte colony-stimulating factor (G
CSF). We performed a tumor biopsy and histological examination revealed
anaplastic carcinoma of the pancreas. Based on the diagnosis, we initiated
chemotherapy using gemcitabine plus S-1. However, the tumor rapidly progressed
and he deteriorated and died 123 days after admission. As immunohistochemical
study showed positive staining for G-CSF in the tumor cell, we diagnosed the
tumor producing G-CSF during autopsy. Anaplastic carcinoma of the pancreas
producing G-CSF is very rare, with 10 cases, including ours, reported in the
literature.
PMID- 27498939
TI - A case of intraductal papillary mucinous neoplasm with high serum pepsinogen II
level.
AB - We report the case of a 65-year-old woman who had a high level of serum
pepsinogen II. Several months earlier, she had found a mass on the right side of
her upper abdomen. Esophagogastroduodenoscopy did not reveal atrophic or
inflammatory findings. She had not taken proton pump inhibitors, and there was no
indication of renal dysfunction. Imaging tests showed a mass of approximately
80mm in the pancreatic head. We performed pancreatoduodenectomy, and the
histopathological examination revealed an intraductal papillary mucinous neoplasm
(IPMN) of gastric type. Serum pepsinogen II levels substantially lowered after
surgery. To the best of our knowledge, this is the first report on a relationship
between IPMN and serum pepsinogen II.
PMID- 27498940
TI - A case of adenosquamous carcinoma of the lower bile duct diagnosed preoperatively
via transpapillary biopsy.
AB - A 78-year-old man presented to our hospital with fever and brownish urine. Upon
thorough examination, a diagnosis of obstructive jaundice and acute cholangitis
associated with a lower bile duct tumor was made. Endoscopic retrograde
cholangiopancreatography revealed entire circumferential stenosis of the lower
bile duct. Examination of a transpapillary biopsy specimen of the lesion
suggested adenosquamous carcinoma. The patient underwent subtotal stomach
preserving pancreaticoduodenectomy. Histopathological examination revealed
adenocarcinoma of the lower bile duct and squamous cell carcinoma components;a
case of adenosquamous carcinoma was accordingly diagnosed. The lower bile duct
tumor directly extended into the pancreatic parenchyma for approximately 1mm. We
performed radical surgery and administered adjuvant chemotherapy with gemcitabine
because of advanced neural invasion after consulting with the patient. There was
no sign of recurrence 46 months after surgery. As adenosquamous carcinoma of the
extrahepatic bile duct is rare, it is difficult to preoperatively diagnose the
condition. Only a few cases have been reported till date.
PMID- 27498941
TI - To the Editor.
PMID- 27498942
TI - In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17
AEPGA and 17-DMAG, with that of the non-water-soluble HSP90 inhibitor, 17-AAG, in
breast cancer cell lines.
AB - Heat shock protein (HSP)90 has emerged as an important target in cancer
therapeutics. Diverse HSP90 inhibitors are under evaluation. The aim of the
present study was to investigate the growth inhibitory effects of the newly
developed water-soluble HSP90 inhibitors, 17-[2-(Pyrrolidin-1-yl)ethyl]amino-17
demethoxygeldanamycin (17-AEPGA) and 17-dimethylaminoethylamino-17
demethoxygeldanamycin (17-DMAG), compared to that of the non-water-soluble HSP90
inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG). The anti
proliferative effects of the 3 drugs on the human breast cancer cell lines, MCF
7, SKBR-3 and MDA-MB-231, were examined in vitro. In addition, tumor progression
factors, including human epidermal growth factor receptor 2 (HER2), epidermal
growth factor receptor 1 (EGFR1) and insulin-like growth factor type 1 receptor
(IGF1R), as well as apoptotic markers were analysed. We found a time- and dose
dependent effect in all the tested cell lines. The effects of 17-AEPGA and 17
DMAG were equal or superior to those of 17-AAG. The 50% growth inhibition
concentration was <2 uM for the water-soluble compounds following 72 h of
exposure. The significant inhibition of HER2, EGFR1 and IGF1R protein expression
was already evident at the concentration of 1 uM. Apoptosis was examined by
caspase-3 and poly(ADP-ribose) polymerase (PARP) assay at the concentration of 1
uM of the inhibitors. HSP70 was upregulated, but HSP27 expression was not
affected. Our data indicate that 17-AEPGA and 17-DMAG are highly active in breast
cancer cell lines and may help to overcome the delivery issues associated with
the use of 17-AAG.
PMID- 27498943
TI - Advances in corneal cell therapy.
AB - Corneal integrity is essential for visual function. Transplantation remains the
most common treatment option for advanced corneal diseases. A global donor
material shortage requires a search for alternative treatments. Different stem
cell populations have been induced to express corneal cell characteristics in
vitro and in animal models. Yet before their application to humans, scientific
and ethical issues need to be solved. The in vitro propagation and implantation
of primary corneal cells has been rapidly evolving with clinical practices of
limbal epithelium transplantation and a clinical trial for endothelial cells in
progress, implying cultivated ocular cells as a promising option for the future.
This review reports on the latest developments in primary ocular cell and stem
cell research for corneal therapy.
PMID- 27498944
TI - High-level hands-free control of wheelchair - a review.
AB - A vital perception in designing human-machine interfaces for people with
disabilities is hands-free control. It is important in setting up communication
among a machine and the part of human body. Nowadays, hands-free control is
extensively used to help disabled people to control the wheelchair. The hands
free control functions are not only helpful to elderly and disabled, but also
useful for normal people who might require using their hands for other tasks at
the same time. As a result, normal people are capable of manipulating multiple
tasks at the same time. The wheelchair is manoeuvred using brainwaves, eyes and
facial muscles movements, voice, tongue, gesture. The mobility using a powered
wheelchair improves the quality of life of the aged people and the people with
mobility impairments significantly. These powered wheelchairs can be actuated
using various high-level control interfaces. In this review, the use of natural
biological signals and non-biological signal to do the hands-free control of
powered wheelchair is presented in this article.
PMID- 27498945
TI - The association between nutritional exposures and metabolic syndrome in the
Tehran Lipid and Glucose Study (TLGS): a cohort study.
AB - OBJECTIVES: This study was conducted with the goal of investigating the effect of
various food consumption on the incidence of metabolic syndrome (MetS). STUDY
DESIGN: Prospective cohort study. METHODS: This study conducted on 3616 healthy
adults aged >=20 years, who were not affected with MetS. Nutritional intake was
determined at the beginning of the study (2008-2011) by the Food Frequency
Questionnaire (FFQ), and the incidence of MetS was investigated after a median of
24.6 months follow-up. Data were analyzed by multiple logistic regression, with
95% confidence interval. RESULTS: After adjusting the effect of other variables
in the model many foods in the whole grains group such as Sangak bread (OR =
0.35, 95% CI: 0.11-1.56), multiple types of vegetables and fruits - such as peach
(OR = 0.11, 95% CI: 0.01-0.75), and mushroom (OR = 0.28, 95% CI: 0.11-0.71) had
protective effects against MetS. From the dairy group yoghurt (OR = 0.43, 95% CI:
0.18-1.01) and ice cream (OR = 0.35, 95% CI: 0.12-1.06) had similar such effects.
CONCLUSION: Based on our findings, there was a significant rise in the incidence
of MetS in Iran. The daily consumption of foods from the whole grains, dairy,
vegetable and fruit groups can help reduce the odds of MetS.
PMID- 27498946
TI - A Step Forward to Empower Global Microbiome Research Through Local Leadership.
PMID- 27498947
TI - Provision of hearing aids to children in Bangladesh: costs and cost-effectiveness
of a community-based and a centre-based approach.
AB - PURPOSE: The aim of this study is to provide evidence on the costs and health
effects of two alternative hearing aid delivery models, a community-based and a
centre-based approach. The study is set in Bangladesh and the study population is
children between 12 and 18 years old. METHODS: Data on resource use by
participants and their caregivers were collected by a household survey. Follow-up
data were collected after two months. Data on the costs to providers of the two
approaches were collected by means of key informant interviews. RESULTS: The
total cost per participant in the community-based model was BDT 6,333 (USD 79)
compared with BDT 13,718 (USD 172) for the centre-based model. Both delivery
models are found to be cost-effective with an estimated cost per DALY averted of
BDT 17,611 (USD 220) for the community-based model and BDT 36,775 (USD 460) for
the centre-based model. CONCLUSIONS: Using a community-based approach to deliver
hearing aids to children in a resource constrained environment is a cost
effective alternative to the traditional centre-based approach. Further evidence
is needed to draw conclusions for scale-up of approaches; rigorous analysis is
possible using well-prepared data collection tools and working closely with
sector professionals. Implications for Rehabilitation Delivery models vary by
resources needed for their implementation. Community-based deliver models of
hearing aids to children in low-income countries are a cost-effective
alternative. The assessment of costs and effects of hearing aids delivery models
in low-income countries is possible through planned collaboration between
researchers and sector professionals.
PMID- 27498949
TI - Association between inflammatory potential of diet and risk of depression in
middle-aged women: the Australian Longitudinal Study on Women's Health.
AB - Dietary factors and inflammation markers have been shown to play a role in the
development of depression. However, there are very few studies that have explored
the association between inflammatory potential of diet and risk of depression. In
this study, we examined the association between the dietary inflammatory index
(DII), which was developed specifically to measure the inflammatory potential of
diet, and risk of depression in the middle-aged cohort of the Australian
Longitudinal Study on Women's Health. A total of 6438 women with a mean age of
52.0 (sd 1.4) years at baseline were followed-up at five surveys over 12 years
(2001-2013). Depression was defined as a score of >=10 on the Center for
Epidemiologic Studies Depression-10 scale. The DII score, a literature-derived,
population-based dietary index that has been validated against several
inflammatory markers, was computed on the basis of dietary intake assessed using
a validated FFQ. Generalised estimating equations were used to estimate relative
risk (RR) of depression according to DII score. Models were adjusted for energy
intake, highest education completed, marital status, menopause status and
symptoms, personal illness or injury, smoking status, physical activity, BMI and
depression diagnosis or treatment. In total, 1156 women (18 %) had scores>=10 on
the CESD scale over the course of 9 years. Women with the most anti-inflammatory
diet had an approximately 20 % lower risk of developing depression compared with
women with the most pro-inflammatory diet (RRDII quartile 1 v. 4: 0.81; 95 % CI
0.69, 0.96; P trend=0.03). These results suggest that an anti-inflammatory diet
is associated with lower risk of depression in middle-aged Australian women.
PMID- 27498950
TI - Insufficient accuracy of the ultrasound-based determination of Achilles tendon
cross-sectional area.
AB - The accurate assessment of the Achilles tendon cross-sectional area (CSA) is a
crucial prerequisite to investigate tendon adaptation and to calculate the tendon
Young's modulus. Besides magnetic resonance imaging (MRI), ultrasonography
emerged as an alternative imaging technique. The purpose of the present study was
to assess the objectivity and reliability of the ultrasound-based methodology and
its validity with respect to the established MRI-based assessment. The Achilles
tendon CSA from 17 healthy males was assessed by ultrasonography at the proximal,
medial and distal position five times each on two separate days and three
observers segmented the CSAs. For the validation, MRI-based CSA measurements were
provided accordingly. The analysis of the ultrasound-based method revealed
significant observer and day effects (p<0.05), despite high intra-class
correlation coefficients for the three observers (>0.93) and both days (>0.89),
respectively. The mean typical percentage error of both days was 7.1%. Comparing
both methods, ultrasonography underestimated (19%) the CSA values obtained by MRI
(p<0.05). Although the correlation coefficients of both methods were high in all
three positions (>0.88), the respective absolute difference of in average 12mm2
and limits of agreement of up to +28mm2 and -2mm2 (~37% of the mean CSA) evidence
considerable inconsistency. Besides the dependency of the CSA determination from
the observer, the ultrasound method is not sensitive enough to detect
physiological changes in tendon morphology of the magnitude that is reported by
intervention studies. Furthermore, the validity analysis revealed a lack of
agreement between both methods. Therefore, the ultrasound-based methodology
cannot be recommended for an accurate Achilles tendon CSA determination in vivo.
PMID- 27498951
TI - Inter-limb differences in impulsive loading following anterior cruciate ligament
reconstruction in females.
AB - Anterior cruciate ligament injury and reconstruction (ACLR) dramatically increase
the risk of knee osteoarthritis, but the contributing factors, and therefore the
targets for intervention, are poorly understood. Differences in loading
characteristics between the ACLR and contralateral limbs during routine
activities such as walking may elucidate the mechanical pathogenesis of post
traumatic knee osteoarthritis. Twenty-nine females with ACLR (age=21.7+/-3.1
years; time since ACL injury=48+/-41 months) performed walking gait at a self
selected speed from which the overall peak vertical ground reaction force (vGRF)
in the first 50% of the stance phase and its linear (slope of the vGRF-time
curve) and instantaneous (first time-derivative) loading rates were calculated.
The magnitude of the vGRF peak immediately following heelstrike and its linear
and instantaneous loading rates were also identified. Subjects were further
classified as "Impulsive Loaders" or "Normal Loaders" based on whether the
transient vGRF peak immediately following heelstrike was objectively classified
as a heelstrike transient in the majority of trials. The vGRF magnitude
immediately following heelstrike and instantaneous loading rates (both overall
and immediately following heelstrike) were greater in the ACLR limb.
Additionally, vGRF linear and instantaneous loading rates were greater in
subjects classified as Impulsive Loaders. As higher loading rates are associated
with greater cartilage degradation in animal models, these data suggest that the
greater loading rates in the ACLR limb may play an important role in development
of post-traumatic knee osteoarthritis. Additionally, the heelstrike transient
appears to be an objective indicator of impulsive loading.
PMID- 27498952
TI - Little evidence for epithelial-mesenchymal transition in a murine model of airway
fibrosis induced by repeated naphthalene exposure.
AB - Recent evidence suggests that epithelial-mesenchymal transition (EMT) is involved
in the pathogenesis of airway obstructive diseases, such as chronic obstructive
pulmonary disease, asthma and bronchiolitis obliterans syndrome after lung
transplantation. However, whether EMT occurs in an experimental model of airway
fibrosis is not well known. We explored evidence of EMT in a murine model of
airway fibrosis induced by repeated exposure to naphthalene. Mice were
administered intraperitoneal injections of naphthalene or corn oil vehicle once
weekly for 14 consecutive weeks. The animals were sacrificed 5days after the
final injection of naphthalene or corn oil vehicle. EMT was evaluated in lung
tissue sections using immunohistochemistry and immunofluorescence. Repeated
naphthalene exposure induced loss of club cells, hyperplasia of epithelial cells
and peribronchial fibrosis. However, we did not find any loss of E-cadherin
expression or any acquisition of vimentin, S100A4 or alphaSMA in epithelial cells
in control or naphthalene-exposed mice. These results suggest that EMT does not
contribute significantly to naphthalene-induced airway fibrosis in mice.
PMID- 27498953
TI - Erratum: Methylphenidate on Cognitive Improvement in Patients with Traumatic
Brain Injury: A Meta-Analysis.
AB - Due to an overlook on the author's side, author's affiliation in the article
entitled as: "Methylphenidate on Cognitive Improvement in Patients with Traumatic
Brain Injury: A Meta-Analysis" by Dr. Chi-Hsien Huang (Co-author) published in
the journal "Current Neuropharmacology" Volume 14, No 3, Page no- 272-281 was
incomplete.
PMID- 27498954
TI - Stones: A novel RNAi therapy for PH1.
PMID- 27498955
TI - Kidney cancer: OCT2 demethylation cracks open oxaliplatin resistance.
PMID- 27498956
TI - Erratum to "Inhibition of botulinum neurotoxins interchain disulfide bond
reduction prevents the peripheral neuroparalysis of botulism" [Biochem.
Pharmacol. 98 (2015) 522-530].
PMID- 27498957
TI - The resveratrol analog HS-1793 enhances radiosensitivity of mouse-derived breast
cancer cells under hypoxic conditions.
AB - Tumor hypoxia is associated with treatment resistance, cell proliferation, and
metastatic potential, all of which contribute to a poor prognosis. Resveratrol
[RES (trans-3,4',5-trihydroxystilbene)], a naturally occurring polyphenol, is
enriched in grapes and red wine. This study investigated whether the resveratrol
analog HS-1793 modulates the hypoxic status and the level of perfusion in mouse
breast cancer FM3A cells. Our data show that HS-1793 decreased the levels of
hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth
factor protein under hypoxic conditions in FM3A cells. HS-1793 improved perfusion
and hypoxic status in tumor tissues and inhibited angiogenesis through HIF-1alpha
suppression in mice. Moreover, HS-1793 inhibited hypoxia-induced cancer stem cell
properties and enhanced ionizing radiation-induced apoptosis in hypoxic FM3A
cells. Collectively, the resveratrol analog HS-1793 might act as a potent
radiosensitizer and be a useful adjuvant agent against radiotherapy-resistant
hypoxic cells in solid tumors.
PMID- 27498958
TI - Aseptic lung and liver abscesses: a diagnostic challenge.
AB - A 67-year-old man known with systemic sarcoidosis was admitted to the department
of internal medicine because of cough and chest pain for several weeks. Thoracic
tomodensitometry demonstrated multiple pulmonary nodules. Biopsies revealed
features compatible with abscesses. Cultures and serologic tests were negative
and the patient was successfully treated with prednisone. Three years later, a
thoraco-abdominal tomodensitometry showed a relapse in the lung and also the
apparition of similar lesions in the liver. Blood test revealed elevated CRP
level at 40 mg/L and mild cholestasis. Biopsies of the liver excluded neoplastic
or infectious diseases and showed inflammatory granulation tissue with abscess
formation. A diagnosis of sarcoidosis-associated aseptic abscesses syndrome was
then made, which was successfully treated with corticosteroids.
PMID- 27498959
TI - Cutaneous peripheral T-cell lymphoma, not otherwise specified: A single-center
prognostic analysis.
AB - BACKGROUND: Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a
rare and aggressive disease either originating in or secondarily involving the
skin. OBJECTIVE: We sought to assess clinical, histopathologic, and prognostic
features of patients with cutaneous PTCL-NOS. METHODS: This was a retrospective
chart review of patients with cutaneous PTCL-NOS between 1993 and 2013. RESULTS:
Thirty patients with PTCL-NOS were included. Fourteen had skin-only disease and
15 had concurrent skin and systemic disease at presentation. In primary cutaneous
PTCL-NOS, the overall survival rate at 5 years was 61% (95% confidence interval,
37-100%; number still at risk, 2). The median overall survival was 5.6 years.
Patients were diagnosed a median of 2.4 months from symptom onset. Patients with
concurrent disease died a median of 2.1 years after diagnosis. The estimated
overall survival rate at 5 years after diagnosis was 29% (95% confidence
interval, 13-67%; number at risk, 3). The median overall survival was 3.9 years.
Patients were diagnosed a median of 6 months from symptom onset, with a 53%
increased risk of death for each year from symptom onset to diagnosis.
LIMITATIONS: This was a retrospective study with a limited number of cases.
CONCLUSIONS: Age at diagnosis and B-symptoms predict poor survival in patients
with cutaneous PTCL-NOS. In addition, poorer survival is observed in patients
with multifocal lesions and concomitant skin and systemic PTCL-NOS.
PMID- 27498960
TI - Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes
based on phase III and long-term extension data in patients with plaque
psoriasis.
AB - BACKGROUND: Psoriasis is a systemic inflammatory condition that is associated
with a higher risk of cardiovascular (CV) disease. Tofacitinib is being
investigated as a treatment for psoriasis. OBJECTIVE: We sought to evaluate the
effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in
patients with plaque psoriasis. METHODS: Changes in select CV risk factors and
the incidence rate (IR) of MACEs were evaluated in patients who were treated with
tofacitinib. RESULTS: Tofacitinib treatment was associated with small, dose
dependent increases in total cholesterol, low-density lipoprotein (LDL), and high
density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was
unchanged. There were no changes in blood pressure and glycated hemoglobin
levels; C-reactive protein levels decreased. The IRs of a MACE were low and
similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib,
the total patient-years of exposure was 5204, with a median follow-up of 527
days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients
with events per 100 patient-years. LIMITATIONS: There was relatively short follow
up time for patients who had MACEs. CONCLUSIONS: While treatment with tofacitinib
is associated with a small increase in cholesterol levels, the total/HDL
cholesterol ratio does not change, there are no unfavorable changes in several CV
risk factors, and the incidence of MACEs is low.
PMID- 27498961
TI - Tunable Heterogeneous Catalysis: N-Heterocyclic Carbenes as Ligands for Supported
Heterogeneous Ru/K-Al2O3 Catalysts To Tune Reactivity and Selectivity.
AB - Here we report, for the first time, an extensive characterization of an N
heterocyclic carbene (NHC)-modified supported heterogeneous catalyst. The
existence of the metal-carbene bond could be proven by (13)C-SS-NMR experiments.
Furthermore, it could be shown that the modification with NHCs does not
structurally change the catalyst itself. The effect of the nature and the loading
of the NHC on the activity and selectivity of the heterogeneous catalyst is
presented by a hydrogenation study, finally leading to an NHC-enabled tunable
heterogeneous catalyst for chemoselective hydrogenation.
PMID- 27498962
TI - Microbacterium faecale sp. nov., isolated from the faeces of Columba livia.
AB - A novel, yellow, aerobic strain, YIM 101168T, isolated from the faeces of a dove
(Columba livia), was studied to determine its taxonomic position. Cells were Gram
stain-positive, short rod-shaped, oxidase-negative, catalase-positive and non
motile. The strain could grow at 7-37 degrees C, at pH 6-10 and in the presence
of 0-13 % (w/v) NaCl. The strain had a 16S rRNA gene sequence similarity and DNA
DNA hybridization relatedness value with Microbacteriumgubbeenense NCIMB 30129T
of 97.8 % and 41.5+/-8.7 %, respectively. Ornithine was detected as the
diagnostic amino acid in the hydrolysate of the cell wall. Whole-cell sugars were
found to be galactose, glucose, rhamnose, mannose and ribose. Major fatty acids
(>10 %) were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. Major menaquinones
were identified as MK-10, MK-11 and MK-12. The polar lipids included
diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, glycolipids
and four unidentified lipids. The phylogenetic analyses as well as the
chemotaxonomic and phenotypic characteristics indicate that strain YIM 101168T
represents a novel species of the genus Microbacterium; the name Microbacterium
faecale sp. nov. is proposed for the novel species and the type strain is YIM
101168T (=DSM 27232T=KCTC 39554T=CGMCC 1.15152T).
PMID- 27498963
TI - Smartphone-enabled optofluidic exosome diagnostic for concussion recovery.
AB - A major impediment to improving the treatment of concussion is our current
inability to identify patients that will experience persistent problems after the
injury. Recently, brain-derived exosomes, which cross the blood-brain barrier and
circulate following injury, have shown great potential as a noninvasive biomarker
of brain recovery. However, clinical use of exosomes has been constrained by
their small size (30-100 nm) and the extensive sample preparation (>24 hr) needed
for traditional exosome measurements. To address these challenges, we developed a
smartphone-enabled optofluidic platform to measure brain-derived exosomes. Sample
to-answer on our chip is 1 hour, 10x faster than conventional techniques. The key
innovation is an optofluidic device that can detect enzyme amplified exosome
biomarkers, and is read out using a smartphone camera. Using this approach, we
detected and profiled GluR2+ exosomes in the post-injury state using both in
vitro and murine models of concussion.
PMID- 27498964
TI - Assessing emergency obstetric care provision in low- and middle-income countries:
a systematic review of the application of global guidelines.
AB - BACKGROUND: Lack of timely and quality emergency obstetric care (EmOC) has
contributed significantly to maternal morbidity and mortality, particularly in
low- and middle-income countries (LMICs). Since 2009, the global guideline,
referred to as the 'handbook', has been used to monitor availability,
utilization, and quality of EmOC. OBJECTIVE: To assess application and explore
experiences of researchers in LMICs in assessing EmOC. DESIGN: Multiple databases
of peer-reviewed literature were systematically reviewed on EmOC assessments in
LMICs, since 2009. Following set criteria, we included articles, assessed for
quality based on a newly developed checklist, and extracted data using a pre
designed extraction tool. We used thematic summaries to condense our findings and
mapped patterns that we observed. To analyze experiences and recommendations for
improved EmOC assessments, we took a deductive approach for the framework
synthesis. RESULTS: Twenty-seven studies met our inclusion criteria, with 17
judged as high quality. The highest publication frequency was observed in 2015.
Most assessments were conducted in Nigeria and Tanzania (four studies each) and
Bangladesh and Ghana (three each). Most studies (17) were done at subnational
levels with 23 studies using the 'handbook' alone, whereas the others combined
the 'handbook' with other frameworks. Seventeen studies conducted facility-based
surveys, whereas others used mixed methods. For different reasons, intrapartum
and very early neonatal death rate and proportion of deaths due to indirect
causes in EmOC facilities were the least reported indicators. Key emerging themes
indicate that data quality for EmOC assessments can be improved, indicators
should be refined, a holistic approach is required for EmOC assessments, and
assessments should be conducted as routine processes. CONCLUSIONS: There is clear
justification to review how EmOC assessments are being conducted. Synergy between
researchers, EmOC program managers, and other key stakeholders would be critical
for improved assessments, which would contribute to increased accountability and
ultimately service provision.
PMID- 27498965
TI - Promoting good health research practice in low- and middle-income countries.
AB - BACKGROUND: Good clinical practice (GCP) guidelines have been the source of
improvement in the quality of clinical trials; however, there are limitations to
the application of GCP in the conduct of health research beyond industry
sponsored clinical trials. The UNICEF/UNDP/World Bank/WHO Special Program for
Research and Training in Tropical Disease is promoting good practice in all
health research involving human through the Good Health Research Practice (GHRP)
training program initiative. OBJECTIVE: To report the results of piloting the
GHRP training program and formulate further steps to harness GHRP for promoting
good practices in all health research involving human, particularly in low- and
middle-income countries (LMICs). DESIGN: The objective of this training is to
impart knowledge and skills for the application of ethical and quality principles
to the design, conduct, recording, and reporting of health research involving
human participants based on the level of risk, to ensure a fit-for-purpose
quality system. This has been formulated into five sequential modules to be
delivered in a 4-day course. Four courses have been organized in the pilot phase
(2014-2015). The courses have been evaluated and assessed based on course
feedback (quantitative and qualitative data) collected during course
implementation and qualitative email-based pre- and post-course evaluation.
RESULTS: Participants were highly satisfied with the course content and its
organization. The relevance and applicability of the course content resulted in
positive feedback and an articulated willingness to adapt and disseminate the
course. Action points to strengthen the training program have been identified,
and showed the imminent need to develop a consensus with a broader range of key
stakeholders on the final set of GHRP standards and means for implementation.
CONCLUSIONS: There is an urgent need to harness the momentum to promote high
quality and ethical health research in LMICs through scaling up GHRP training and
further development of GHRP principles into international standards.
PMID- 27498967
TI - Silicimonas algicola gen. nov., sp. nov., a member of the Roseobacter clade
isolated from the cell surface of the marine diatom Thalassiosira delicatula.
AB - A Gram-negative, aerobic, non-motile bacterium, designated strain KC90BT, was
isolated from the surface of a cell of the marine diatom Thalassiosira
delicatula. The bacterial cells were pleomorphic and formed very small, beige
colonies on marine agar. Optimal growth was obtained at 25 degrees C, at pH 6.5
7.5 and in the presence of 1.5-2.0 % (w/v) NaCl. Phylogenetic analyses based on
its 16S rRNA gene sequence revealed that strain KC90BT belonged to the
Roseobacter clade and formed a monophyletic cluster with the sequences of
Boseongicola aestuarii, Profundibacterium mesophilum, Hwanghaeicola aestuarii,
Maribius pelagius and M. salinus, showing 91.4-95.7 % sequence similarities.
Ubiquinone Q-10 was the predominant lipoquinone but a significant amount of
ubiquinone Q-9 was also detected. The major cellular fatty acids were C18 :
1omega7c, 11-methyl C18 : 1omega7c and C18 : 0. Strain KC90BT also contained
specific fatty acids (C17 : 0, anteiso-C15 : 0 and anteiso-C17 : 0) that were not
detected in its closest described relatives. The major polar lipids of strain
KC90BT comprised phosphatidylglycerol, phosphatidylcholine,
diphosphatidylglycerol and an unidentified aminolipid. The DNA G+C content of
strain KC90BT was 65.2 mol%. The phylogenetic analysis of strain KC90BT, together
with the differential phenotypic and chemotaxonomic properties demonstrate that
strain KC90BT is distinct from type strains of B. aestuarii, P. mesophilum, H.
aestuarii, M. pelagius and M. salinus. Based on the data presented in this study,
strain KC90BT represents a novel genus and species within the family
Rhodobacteraceae, for which the name Silicimonas algicola gen. nov., sp. nov. is
proposed. The type strain is KC90BT (=DSM 103371T=RCC 4681T).
PMID- 27498966
TI - Neural changes in the primate brain correlated with the evolution of complex
motor skills.
AB - Complex motor skills of eventual benefit can be learned after considerable trial
and error. What do structural brain changes that accompany such effortful long
term learning tell us about the mechanisms for developing innovative behavior?
Using MRI, we monitored brain structure before, during and after four marmosets
learnt to use a rake, over a long period of 10-13 months. Throughout learning,
improvements in dexterity and visuo-motor co-ordination correlated with increased
volume in the lateral extrastriate cortex. During late learning, when the most
complex behavior was maintained by sustained motivation to acquire the skill, the
volume of the nucleus accumbens increased. These findings reflect the
motivational state required to learn, and show accelerated function in higher
visual cortex that is consistent with neurocognitive divergence across a spectrum
of primate species.
PMID- 27498968
TI - Molecular phylogenetic analysis of nuclear genes suggests a Cenozoic over-water
dispersal origin for the Cuban solenodon.
AB - The Cuban solenodon (Solenodon cubanus) is one of the most enigmatic mammals and
is an extremely rare species with a distribution limited to a small part of the
island of Cuba. Despite its rarity, in 2012 seven individuals of S. cubanus were
captured and sampled successfully for DNA analysis, providing new insights into
the evolutionary origin of this species and into the origins of the Caribbean
fauna, which remain controversial. We conducted molecular phylogenetic analyses
of five nuclear genes (Apob, Atp7a, Bdnf, Brca1 and Rag1; total, 4,602 bp) from
35 species of the mammalian order Eulipotyphla. Based on Bayesian relaxed
molecular clock analyses, the family Solenodontidae diverged from other
eulipotyphlan in the Paleocene, after the bolide impact on the Yucatan Peninsula,
and S. cubanus diverged from the Hispaniolan solenodon (S. paradoxus) in the
Early Pliocene. The strikingly recent divergence time estimates suggest that S.
cubanus and its ancestral lineage originated via over-water dispersal rather than
vicariance events, as had previously been hypothesised.
PMID- 27498969
TI - Campylobacter hepaticus sp. nov., isolated from chickens with spotty liver
disease.
AB - Ten strains of an unknown Campylobacter species were isolated from the livers of
chickens with spotty liver disease in Australia. The strains were Gram-stain
negative, microaerobic, catalase- and oxidase-positive and urease-negative.
Unlike most other species of the genus Campylobacter, most of the tested strains
of this novel species hydrolysed hippurate and half of them could not reduce
nitrate. All strains showed resistance, or intermediate resistance, to nalidixic
acid and most of them were resistant to cephalothin. Examination of negatively
stained cells under transmission electron microscopy revealed that they were S
shaped, with bipolar unsheathed flagella. Phylogenetic analyses based on the 16S
rRNA gene and the heat shock protein 60 (hsp60) gene sequences indicated that the
strains formed a robust clade that was clearly distinct from recognized
Campylobacter species. Unusually, they had a DNA G+C content of 27.9 mol%, lower
than any previously described Campylobacter species, and they showed less than 84
% average nucleotide identity to the nearest sequenced species. Taken together,
these data indicate that the strains belong to a novel Campylobacter species, for
which the name Campylobacter hepaticus sp. nov. is proposed. The type strain is
HV10T (=NCTC 13823T=CIP 111092T).
PMID- 27498970
TI - The Influence of Surface Topography and Surface Chemistry on the Anti-Adhesive
Performance of Nanoporous Monoliths.
AB - We designed spongy monoliths allowing liquid delivery to their surfaces through
continuous nanopore systems (mean pore diameter ~40 nm). These nanoporous
monoliths were flat or patterned with microspherical structures a few tens of
microns in diameter, and their surfaces consisted of aprotic polymer or of TiO2
coatings. Liquid may reduce adhesion forces FAd; possible reasons include
screening of solid-solid interactions and poroelastic effects. Softening-induced
deformation of flat polymeric monoliths upon contact formation in the presence of
liquids enhanced the work of separation WSe. On flat TiO2-coated monoliths, WSe
was smaller under wet conditions than under dry conditions, possibly because of
liquid-induced screening of solid-solid interactions. Under dry conditions, WSe
is larger on flat TiO2-coated monoliths than on flat monoliths with a polymeric
surface. However, under wet conditions, liquid-induced softening results in
larger WSe on flat monoliths with a polymeric surface than on flat monoliths with
an oxidic surface. Monolithic microsphere arrays show antiadhesive properties;
FAd and WSe are reduced by at least 1 order of magnitude as compared to flat
nanoporous counterparts. On nanoporous monolithic microsphere arrays, capillarity
(WSe is larger under wet than under dry conditions) and solid-solid interactions
(WSe is larger on oxide than on polymer) dominate contact mechanics. Thus, the
microsphere topography reduces the impact of softening-induced surface
deformation and screening of solid-solid interactions associated with liquid
supply. Overall, simple modifications of surface topography and chemistry
combined with delivery of liquid to the contact interface allow adjusting WSe and
FAd over at least 1 order of magnitude. Adhesion management with spongy monoliths
exploiting deployment (or drainage) of interfacial liquids as well as induction
or prevention of liquid-induced softening of the monoliths may pave the way for
the design of artificial surfaces with tailored contact mechanics. Moreover, the
results reported here may contribute to better understanding of the contact
mechanics of biological surfaces.
PMID- 27498971
TI - Catalyst-free dehydrocoupling of amines, alcohols, and thiols with pinacol borane
and 9-borabicyclononane (9-BBN).
AB - Contrary to recent reports, the dehydrocoupling of pinacol borane and 9
borabicyclononane with a variety of amines, alcohols and thiols can be achieved
under mild conditions without catalyst. This process involves the formation of
Lewis acid-base adducts featuring a hydridic B-H in close proximity to an acidic
Nu-H.
PMID- 27498972
TI - Characterization of multidrug-resistant osteosarcoma sublines and the molecular
mechanisms of resistance.
AB - Multidrug resistance (MDR) is a challenge for the treatment of cancer and the
underlying molecular mechanisms remain elusive. The current study exposed MG63
osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish
four VCR-resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug
resistance indices (RI) of these sublines was detected with the CCK-8 assay and
determined to be163, 476, 1,247, and 2,707-fold higher than that of parental
cells, respectively. These sublines also exhibited cross-resistance to
doxorubicin, paclitaxel and pirarubicin. With increased RI, the proliferative
capacity of these sublines was gradually reduced and cell morphology was also
altered, characterized by increased formation of pseudopodia and long cytoplasmic
processes at opposite poles. However, the migration capacity and expression of
certain drug resistance-associated genes were not in accordance with the
increased RI; multidrug resistance protein 1 (MDR1) expression was significantly
increased in these sublines compared with parental cells. However, in the highly
resistant MG63/VCR3 and MG63/VCR4 cells, MDR-associated protein 1, topoisomerase
II and LIM domain kinase 1 levels were significantly reduced compared with the
moderately resistant MG63/VCR2 cells. Expression of glutathione S-transferase-pi
mRNA was determined using reverse transcription-quantitative polymerase chain
reaction and determined that it was not changed between MG63 and MG63/VCR cells.
The data of the present study demonstrated that the molecular alterations of drug
resistance may change with the degree of drug resistance. Taking cell morphology
into consideration, the intratumor clonal and phenotypic heterogeneity may be
responsible for drug resistance. These MG63/VCR sublines may be a valuable tool
to assess drug resistance and the underlying mechanisms, and to identify novel
drug resistance-associated genes or strategies to overcome MDR in human
osteosarcoma.
PMID- 27498974
TI - Salt Intake in an Adult Population of Bangladesh.
PMID- 27498973
TI - Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological
activity against invasive breast cancer cells.
AB - We describe the biological effects of a polyphenol-rich strawberry extract
(PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive
basal-like breast cancer cell line A17. Dose-response and time-course experiments
showed that PRSE is able to decrease the cellular viability of A17 cells in a
time- and dose-dependent manner. PRSE effect on cell survival was investigated in
other tumor and normal cell lines of both mouse and human origin, demonstrating
that PRSE is more active against breast cancer cells. Cytofluorimetric analysis
of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of
cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle.
In addition, the migration of A17 cells was studied monitoring the ability of
PRSE to inhibit cellular mobility. Gene expression analysis revealed the
modulation of 12 genes playing different roles in the cellular migration,
adhesion and invasion processes. Finally, in vivo experiments showed the growth
inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed
with PRSE. Overall, we demonstrated that PRSE exerts important biological
activities against a highly invasive breast cancer cell line both in vitro and in
vivo suggesting the strawberry extracts as preventive/curative food strategy.
PMID- 27498975
TI - Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii in South
America.
AB - One hundred and twenty-six epidemiologically sequential, unrelated, carbapenem
resistant Acinetobacter baumannii isolates from nine hospitals in six countries
of South America were collected between July 2013 and June 2014. Genes coding for
Ambler class D and B carbapenemases were sought by PCR. All isolates were typed
using the 3-locus sequence typing and blaOXA-51-like sequence-based typing
techniques. The blaOXA-23 gene was recovered in all the participating hospitals
and in all the isolates of seven of nine medical centres. The blaOXA-72 gene was
only recovered in the two medical centres from Guayaquil city, Ecuador. Trilocus
sequence typing revealed the presence of sequence groups SG2, SG4 and SG5. blaOXA
51-like sequence-based typing revealed the presence of blaOXA-132, blaOXA-65,
blaOXA-69 and blaOXA-64. Our results showed that the population of carbapenem
resistant A. baumannii in South America was principally associated with ST79,
ST25 and ST15 (92 %) and harboured the blaOXA-23 gene mainly. CC2 was not
detected.
PMID- 27498976
TI - Association of angiotensin-converting enzyme insertion/deletion polymorphism with
type 1 diabetic nephropathy: a meta-analysis.
AB - OBJECTIVE: This study aimed to systematically evaluate the effect of an
angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism on
type 1 diabetic nephropathy (DN). METHODS: Cochrane Library, Embase, PubMed,
Science Direct, Web of science, Wanfang data, VIP database, China Knowledge
Resource Integrated Database, and SinoMed were searched. A total of 17 case
control studies analyzing ACE I/D polymorphism and type 1 DN risk were included
in the present meta-analysis. RESULTS: Overall, a significant increased risk was
found in allele comparison (OR = 1.16, 95% CI = 1.05-1.28, p = 0.04), dominant
comparison (OR = 1.56, 95% CI = 1.14-2.15, p = 0.006) and homozygote comparison
(OR = 1.52, 95% CI = 1.06-2.19, p = 0.02). In subgroup analyses according to
ethnicity, the risk of type 1 DN in Asian population was increased in allele
comparison (OR = 1.98, 95% CI = 1.15-3.42, p = 0.01), recessive comparison (OR =
2.48, 95% CI = 1.51-4.10, p = 0.0004), dominant comparison (OR = 3.15, 95% CI =
1.90-5.23, p < 0.00001), and homozygote comparison (OR = 2.87, 95% CI = 1.02
8.06, p = 0.05). However, there was no association between the ACE I/D genetic
variants and type 1 DN in Caucasian populations. CONCLUSIONS: Our meta-analysis
results indicate that the ACE I/D polymorphism may contribute to type 1 DN
development, especially in the Asian groups with type 1 diabetes. The current
findings need to be confirmed by future well-designed and larger sample size
primary studies in populations with different ethnicities.
PMID- 27498978
TI - Multi Stakeholders' Attitudes toward Bt rice in Southwest, Iran: Application of
TPB and Multi Attribute Models.
AB - Organisms that have been genetically engineered and modified (GM) are referred to
as genetically modified organisms (GMOs). Bt crops are plants that have been
genetically modified to produce certain proteins from the soil bacteria Bacillus
thuringiensis (Bt), which makes these plants resistant to certain lepidopteran
and coleopteran species. Genetically Modified (GM) rice was produced in 2006 by
Iranian researchers from Tarom Mowla'ii and has since been called 'Bt rice'. As
rice is an important source of food for over 3 billion inhabitants on Earth, this
study aims to use a correlational survey in order to shed light on the predicting
factors relating to the extent of stakeholders' behavioral intentions towards Bt
rice. It is assumed and the results confirm that "attitudes toward GM crops" can
be used as a bridge in the Attitude Model and the Behavioral Intention Model in
order to establish an integrated model. To this end, a case study was made of the
Southwest part of Iran in order to verify this research model. This study also
revealed that as a part of the integrated research framework in the Behavior
Intention Model both constructs of attitude and the subjective norm of the
respondents serve as the predicting factors of stakeholders' intentions of
working with Bt rice. In addition, the Attitude Model, as the other part of the
integrated research framework, showed that the stakeholders' attitudes toward Bt
rice can only be determined by the perceived benefits (e.g. positive outcomes) of
Bt rice.
PMID- 27498977
TI - MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated
PI3K/AKT pathway in human non-small lung cancer.
AB - Abnormal expression of microRNA-107 (miR-107) was found in non-small cell lung
cancer (NSCLC). However, little is known about its role and molecular mechanism
in NSCLC progression and metastasis. Therefore, the aims of this study were to
clarify the potential role of miR-107 and molecular mechanism in NSCLC
progression and metastasis. Quantitative real-time polymerase chain reaction
assay showed that miR-107 expression levels were significantly decreased in NSCLC
tissue and cell lines. Low miR-107 levels in tumor tissue correlated with
advanced TNM stage and lymph node metastasis. Function assays showed that
overexpression of miR-107 suppressed cell proliferation, migration and invasion
in A549 cells in vitro, and inhibited NSCLC tumor growth in vivo. Further
mechanism assays suggested the brain-derived neurotrophic factor (BDNF) was
identified as a target gene of miR-107 in NSCLC cells. In addition, BDNF
expression was upregulated, and inversely correlated with miR-107 in NSCLC
tissues. Enforced overexpression of BDNF effectively reversed the tumor
suppressive functions of miR-107 on NSCLC proliferation, migration and invasion.
miR-107 overexpression or downregulation of BDNF was able to inhibit activation
of PI3K/AKT signaling pathway. Taken together, our findings present the first
evidence that miR-107 could suppress NSCLC metastasis by targeting BDNF and
indirectly regulating PI3K/AKT signaling pathway, which might lead to a potential
therapeutic strategy focusing on miR-107 and BDNF for human NSCLC.
PMID- 27498979
TI - Room-temperature synthesis of nanoporous 1D microrods of graphitic carbon nitride
(g-C3N4) with highly enhanced photocatalytic activity and stability.
AB - A one-dimensional (1D) nanostructure having a porous network is an exceptional
photocatalytic material to generate hydrogen (H2) and decontaminate wastewater
using solar energy. In this report, we synthesized nanoporous 1D microrods of
graphitic carbon nitride (g-C3N4) via a facile and template-free chemical
approach at room temperature. The use of concentrated acids induced etching and
lift-off because of strong oxidation and protonation. Compared with the bulk g
C3N4, the porous 1D microrod structure showed five times higher photocatalytic
degradation performance toward methylene blue dye (MB) under visible light
irradiation. The photocatalytic H2 evolution of the 1D nanostructure (34 MUmol g(
1)) was almost 26 times higher than that of the bulk g-C3N4 structure (1.26 MUmol
g(-1)). Additionally, the photocurrent stability of this nanoporous 1D morphology
over 24 h indicated remarkable photocorrosion resistance. The improved
photocatalytic activities were attributed to prolonged carrier lifetime because
of its quantum confinement effect, effective separation and transport of charge
carriers, and increased number of active sites from interconnected nanopores
throughout the microrods. The present 1D nanostructure would be highly suited for
photocatalytic water purification as well as water splitting devices. Finally,
this facile and room temperature strategy to fabricate the nanostructures is very
cost-effective.
PMID- 27498980
TI - Pathways to self-organization: Crystallization via nucleation and growth.
AB - Crystallization, a prototypical self-organization process during which a
disordered state spontaneously transforms into a crystal characterized by a
regular arrangement of its building blocks, usually proceeds by nucleation and
growth. In the initial stages of the transformation, a localized nucleus of the
new phase forms in the old one due to a random fluctuation. Most of these nuclei
disappear after a short time, but rarely a crystalline embryo may reach a
critical size after which further growth becomes thermodynamically favorable and
the entire system is converted into the new phase. In this article, we will
discuss several theoretical concepts and computational methods to study
crystallization. More specifically, we will address the rare event problem
arising in the simulation of nucleation processes and explain how to calculate
nucleation rates accurately. Particular attention is directed towards discussing
statistical tools to analyze crystallization trajectories and identify the
transition mechanism.
PMID- 27498981
TI - Segregation of chain ends to the surface of a polymer melt: Effect of surface
profile versus chain discreteness.
AB - Silberberg has argued that the surface of a polymer melt behaves like a
reflecting boundary on the random-walk statistics of the polymers. Although this
is approximately true, independent studies have shown that violations occur due
to the finite width of the surface profile and to the discreteness of the polymer
molecule, resulting in an excess of chain ends at the surface and a reduction in
surface tension inversely proportional to the chain length, N . Using self
consistent field theory (SCFT), we compare the magnitude of these two effects by
examining a melt of discrete polymers modeled as N monomers connected by Hookean
springs of average length, a , next to a polymer surface of width [Formula: see
text]. The effects of the surface width and the chain discreteness are found to
be comparable for realistic profiles of [Formula: see text] ~ a. A semi
analytical approximation is developed to help explain the behavior. The relative
excess of ends at the surface is dependent on the details of the model, but in
general it decreases for shorter polymers. The excess is balanced by a long-range
depletion that has a universal shape independent of the molecular details.
Furthermore, the approximation predicts that the reduction in surface energy
equals one unit of kBT for every extra chain end at the surface.
PMID- 27498982
TI - Robust Sierpinski triangle fractals on symmetry-mismatched Ag(100).
AB - Sierpinski triangle fractals were constructed on both Ag(111) and symmetry
mismatched fourfold Ag(100) surfaces through chemical reaction between H3PH
molecules and Fe atoms under vacuum. Density functional theory calculations
revealed that the fractals were stabilized by the strong coordination interaction
between Fe and O atoms. In comparison, pure H3PH molecules formed fractals via
moderately strong hydrogen bonds only on Ag(111), not on Ag(100).
PMID- 27498983
TI - An Exploration of Behavioral Health Productivity and Billing Practices Within
Pediatric Primary Care.
AB - OBJECTIVES : To provide descriptive information on behavioral health (BH)
productivity and billing practices within a pediatric primary care setting.
METHODS : This retrospective investigation reviewed 30 months of electronic
medical records and financial data. RESULTS : The percent of BH provider time
spent in direct patient care (productivity) was 35.28% overall, with a slightly
higher quarterly average (M = 36.42%; SD = 6.46%). In the 646.75 hr BH
providers spent in the primary care setting, $52,050.00 was charged for BH
services delivered ($80.48 hourly average). CONCLUSIONS : BH productivity and
billing within pediatric primary care were suboptimal and likely multifactorially
derived. To promote integrated primary care sustainability, the authors recommend
three future aims: improve BH productivity, demonstrate the value-added
contributions of BH services within primary care, and advocate for BH-supporting
health care reform.
PMID- 27498985
TI - Marinifilum albidiflavum sp. nov., isolated from coastal sediment.
AB - A novel Gram-stain-negative, facultatively anaerobic, filamentous, and yellowish
white-pigmented marine bacterium, designated strain FB208T, was isolated from
marine sediment obtained off the coastal area of Weihai, China. Cells of strain
FB208T were filamentous during exponential growth, fragmented to rods in the
stationary growth phase and became spherical in aged cultures. It grew optimally
at 33 degrees C, at pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl.
Based on the 16S rRNA gene sequence, strain FB208T was found to be closely
related to Marinifilum flexuosum DSM 21950T (96.9 % similarity) and Marinifilum
fragile JCM 15579T (96.4 %), with less than 90.0 % sequence similarity to other
genera of the class Bacteroidia. Phylogenetic analysis, also based on 16S rRNA
gene sequences, placed strain FB208T in the genus Marinifilum, family
Marinifilaceae. The predominant isoprenoid quinone of strain FB208T was
identified as menaquinone MK-7. The main cellular fatty acids were iso-C15 : 0,
iso-C17 : 0 3-OH and iso-C17 : 1omega9c, and the major polar lipids were an
unidentified lipid and aminophospholipid. The G+C content of the genomic DNA was
43.8 mol%. Based on these phylogenetic and phenotypic data, strain FB208T
represents a novel species of the genus Marinifilum, for which the name
Marinifilum albidiflavum sp. nov. is proposed. The type strain is FB208T (=KCTC
42591T=MCCC 1H00113T).
PMID- 27498986
TI - Quantitative determination of activation energies in mechanochemical reactions.
AB - Mechanochemical reactions often result in 100% yields of single products, making
purifying procedures obsolete. Mechanochemistry is also a sustainable and eco
friendly method. The ever increasing interest in this method is contrasted by a
lack in mechanistic understanding of the mechanochemical reactivity and
selectivity. Recent in situ investigations provided direct insight into formation
pathways. However, the currently available theories do not predict temperature T
as an influential factor. Here, we report the first determination of an apparent
activation energy for a mechanochemical reaction. In a temperature-dependent in
situ study the cocrystallisation of ibuprofen and nicotinamide was investigated
as a model system. These experiments provide a pivotal step towards a
comprehensive understanding of milling reaction mechanisms.
PMID- 27498987
TI - Guar gum as a new antimicrobial peptide delivery system against diabetic foot
ulcers Staphylococcus aureus isolates.
AB - Diabetic patients frequently develop diabetic foot ulcers (DFUs), particularly
those patients vulnerable to Staphylococcus aureus opportunistic infections. It
is urgent to find new treatments for bacterial infections. The antimicrobial
peptide (AMP) nisin is a potential candidate, mainly due to its broad spectrum of
action against pathogens. Considering that AMP can be degraded or inactivated
before reaching its target at therapeutic concentrations, it is mandatory to
establish effective AMP delivery systems, with the natural polysaccharide guar
gum being one of the most promising. We analysed the antimicrobial potential of
nisin against 23 S. aureus DFU biofilm-producing isolates. Minimum inhibitory
concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm
inhibitory concentration (MBIC) and minimum biofilm eradication concentration
(MBEC) were determined for nisin diluted in HCl and incorporated in guar gum gel.
Statistical analysis was performed using the Wilcoxon matched-pair test. Nisin
was effective against all isolates, including some multidrug-resistant clinical
isolates, independent of whether it is incorporated in guar gum. While
differences among MIC, MBC and MBIC values were observed for HCl- and guar gum-
nisin, no significant differences were found between MBEC values. Inhibitory
activity of both systems seems to differ only twofold, which does not compromise
guar gum gel efficiency as a delivery system. Our results highlight the potential
of nisin as a substitute for or complementary therapy to current antibiotics used
for treating DFU infections, which is extremely relevant considering the increase
in multidrug-resistant bacteria dissemination. The guar gum gel represents an
alternative, practical and safe delivery system for AMPs, allowing the
development of novel topical therapies as treatments for bacterial skin
infections.
PMID- 27498989
TI - Polaribacter marinaquae sp. nov., isolated from seawater.
AB - A novel Gram-stain-negative, rod-shaped, non-spore-forming, non-flagellated,
strictly aerobic strain, designated RZW3-2T, was isolated from seawater from near
the Yellow Sea coast of PR China (35.475 degrees N 119.613 degrees E). The
organism grew optimally between 24 and 28 degrees C, at pH 6.0-7.0 and in the
presence of 2-3 % (w/v) NaCl. The strain requires seawater or artificial seawater
for growth and NaCl alone does not support growth. RZW3-2T contained iso-C15 : 0,
C16 : 1omega7c and/or C16 : 1omega6c and anteiso-C15 : 0 as the dominant fatty
acids. The respiratory quinone detected in RZW3-2T was menaquinone 6 (MK6). The
polar lipids of RZW3-2T comprised phosphatidylethanolamine (PE), four
unidentified phospholipids (PL), two unidentified aminolipids (AL) and one
unknown lipid (L). The DNA G+C content of RZW3-2T was 30.5 mol%. Phylogenetic
analysis based on 16S rRNA gene sequences showed that the novel strain was
related most closely to Polaribacter reichenbachii KCTC 23969T, Polaribacter
dokdonensis KCTC 12392T and Polaribacter irgensii CIP 106478T with 98.0, 97.8 and
97.0 % sequence similarities, respectively. The DNA-DNA hybridization values
between RZW3-2T and its closest phylogenetic relatives, P. reichenbachii KCTC
23969T and P. dokdonensis KCTC 12392T, were 52.0+/-0.6 % and 49.8+/-1.21 %
respectively. On the basis of polyphasic analyses, RZW3-2T represents a novel
species of the genus Polaribacter, for which the name Polaribacter marinaquae sp.
nov. is proposed. The type strain is RZW3-2T (=JCM 30825T=KCTC 42664T=MCCC
1K00696T).
PMID- 27498988
TI - Oral Squamous Carcinoma Cells Express B7-H1 and B7-DC Receptors in Vivo.
AB - B7-H1 and B7-DC ligands are members of the B7 family with important regulatory
functions in cell-mediated immune response. Both receptors are ligands of the
programmed death receptor PD-1. B7-H1 expression has been detected in the
majority of human carcinomas in vivo. B7-H1 mediated signals are able to
negatively regulate activated T cell functions and survival, and enable tumor
cells to overcome host response. The aim of this study was to investigate the
expression of B7-H1 and B7-DC proteins in oral squamous cell carcinomas (OSCC) in
vivo. Tissues from 15 samples were cryo-sected and following histological routine
staining (HE), incubated with antibodies against human B7-H1 and B7-DC. Immuno
staining of pan-cytokeratin was performed to ascertain the epithelial origin of
the tissue and CK 19 to demonstrate the proliferating stage. Confocal laser
scanning microscopy confirmed the presence of both B7-H1 and B7-DC in all 15
OSCC. The B7-H1 and B7-DC staining was located in areas of the tissue that were
identified as cancerous lesions in the previously stained HE sections before.
Staining with Pan-CK and CK19 provided evidence for the epithelial origin and the
proliferating stage of the tissue. The in vivo expression of the B7-H1 and B7-DC
receptors in oral squamous cell carcinomas suggest that general mechanisms for
immune evasion of tumors are also found in OSCC.
PMID- 27498990
TI - The Other Face of the Nucleus Accumbens: Aversion.
PMID- 27498991
TI - Innate immunity and the sensing of infection, damage and danger in the female
genital tract.
AB - Tissue homeostasis in the female genital tract is challenged by infection,
damage, and even physiological events during reproductive cycles. We propose that
the evolutionarily ancient system of innate immunity is sufficient to sense and
respond to danger in the non-pregnant female genital tract. Innate immunity
produces a rapidly inducible, non-specific response when cells sense danger. Here
we provide a primer on innate immunity and discuss what is known about how danger
signals are sensed in the endometrium and ovary, the impact of inflammatory
responses on reproduction, and how endocrinology and innate immunity are
integrated. Endometrial epithelial and stromal cells, and ovarian granulosa cells
express pattern recognition receptors, similar to cells of the innate immune
system. These pattern recognition receptors, such as the Toll-like receptors,
bind pathogen-associated or damage-associated molecular patterns. Activation of
pattern recognition receptors leads to inflammation, recruitment of immune cells
from the peripheral circulation, and phagocytosis. Although the inflammatory
response helps maintain or restore endometrial health, there may also be negative
consequences for fertility, including perturbation of oocyte competence. The
intensity of the inflammatory response reflects the balance between the level of
danger and the systems that regulate innate immunity, including the endocrine
environment. Understanding innate immunity is important because disease and
inappropriate inflammatory responses in the endometrium or ovary cause
infertility.
PMID- 27498992
TI - Nonlinear machine learning and design of reconfigurable digital colloids.
AB - Digital colloids, a cluster of freely rotating "halo" particles tethered to the
surface of a central particle, were recently proposed as ultra-high density
memory elements for information storage. Rational design of these digital
colloids for memory storage applications requires a quantitative understanding of
the thermodynamic and kinetic stability of the configurational states within
which information is stored. We apply nonlinear machine learning to Brownian
dynamics simulations of these digital colloids to extract the low-dimensional
intrinsic manifold governing digital colloid morphology, thermodynamics, and
kinetics. By modulating the relative size ratio between halo particles and
central particles, we investigate the size-dependent configurational stability
and transition kinetics for the 2-state tetrahedral (N = 4) and 30-state
octahedral (N = 6) digital colloids. We demonstrate the use of this framework to
guide the rational design of a memory storage element to hold a block of text
that trades off the competing design criteria of memory addressability and
volatility.
PMID- 27498993
TI - Conscientious objection to abortion.
PMID- 27498994
TI - Evaluation of CT-based SUV normalization.
AB - The purpose of this study was to determine patients' lean body mass (LBM) and
lean tissue (LT) mass using a computed tomography (CT)-based method, and to
compare standardized uptake value (SUV) normalized by these parameters to
conventionally normalized SUVs. Head-to-toe positron emission tomography (PET)/CT
examinations were retrospectively retrieved and semi-automatically segmented into
tissue types based on thresholding of CT Hounsfield units (HU). The following HU
ranges were used for determination of CT-estimated LBM and LT (LBMCT and LTCT):
180 to -7 for adipose tissue (AT), -6 to 142 for LT, and 143 to 3010 for bone
tissue (BT). Formula-estimated LBMs were calculated using formulas of James (1976
Research on Obesity: a Report of the DHSS/MRC Group (London: HMSO)) and
Janmahasatian et al (2005 Clin. Pharmacokinet. 44 1051-65), and body surface area
(BSA) was calculated using the DuBois formula (Dubois and Dubois 1989 Nutrition 5
303-11). The CT segmentation method was validated by comparing total patient body
weight (BW) to CT-estimated BW (BWCT). LBMCT was compared to formula-based
estimates (LBMJames and LBMJanma). SUVs in two healthy reference tissues, liver
and mediastinum, were normalized for the aforementioned parameters and compared
to each other in terms of variability and dependence on normalization factors and
BW. Comparison of actual BW to BWCT shows a non-significant difference of 0.8 kg.
LBMJames estimates are significantly higher than LBMJanma with differences of 4.7
kg for female and 1.0 kg for male patients. Formula-based LBM estimates do not
significantly differ from LBMCT, neither for men nor for women. The coefficient
of variation (CV) of SUV normalized for LBMJames (SUVLBM-James) (12.3%) was
significantly reduced in liver compared to SUVBW (15.4%). All SUV variances in
mediastinum were significantly reduced (CVs were 11.1-12.2%) compared to SUVBW
(15.5%), except SUVBSA (15.2%). Only SUVBW and SUVLBM-James show independence
from normalization factors. LBMJames seems to be the only advantageous SUV
normalization. No advantage of other SUV normalizations over BW could be
demonstrated.
PMID- 27498995
TI - Sero-epidemiological analysis of vertical transmission relative risk of Borna
disease virus infection in dairy herds.
AB - Borna disease virus (BDV) is a virus that causes a neurological disease in
domestic animals, including a variety of animal species in Japan. Few studies
have examined the mode of transmission of this virus in cattle, and the exact
mechanisms underlying the transmission of the virus need to be elucidated. This
study aimed to examine the contribution of vertical transmission of the virus,
which occurs when the virus is transmitted from the mother to offspring during
gestation or birth. We used an epidemiological approach. The relative risk (RR)
was calculated for cattle born to BDV sero-positive cows from farms with a higher
within-herd prevalence of BDV (56.8%). We tested the sera of 1,122 dairy cattle
from 24 dairy herds in Hokkaido Prefecture, Japan, for BDV infection using the
ELISA and western blotting method. The overall level of BDV sero-prevalence was
22.1%. Seroprevalence was significantly higher in closed-breeding herds that do
not have buying in cows (39.7%) than in farms that restock cattle by buying in
cows (4.4%, P<0.01). The overall RR of BDV vertical transmission from infected
mothers to their daughters was 1.86 (95% confidence interval (CI): 1.54-2.56).
Our results show that vertical transmission contributes significantly to BDV
transmission in the farms tested in this study.
PMID- 27498996
TI - Recovery with a regular dose of antibiotics from bacillary hemoglobinuria in a
Holstein cow.
AB - One Holstein cow housed with 21 other cows exhibited clinical signs of pyrexia,
anorexia and diarrhea along with severe hemoglobinuria. Hematological and
biochemical analyses conducted before and after antibiotic therapy indicated
severe hemolytic anemia and disruption of hepatic function. A general improvement
in conditions was observed after an 11-day program of treatment comprising a
regular dose of antibiotics and prescribed supportive therapies. A tentative
diagnosis of bacillary hemoglobinuria was made based on the clinical and clinico
pathologic features on day 7. A molecular diagnosis was made by a PCR
amplification of the flagellin gene of Clostridium haemolyticum using DNA
extracted from the whole blood. The cow was diagnosed with the first recorded
occurrence of bacillary hemoglobinuria of Holstein cattle in Japan.
PMID- 27498997
TI - Discovery of anti-inflammatory role of prostaglandin D2.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin are one of the
most frequently used classes of drug worldwide and inhibit prostaglandin (PG)
production by inhibiting cyclooxygenase activity. Although NSAIDs are broadly
used against inflammatory diseases, they have side effects including alimentary
canal disorders, kidney damage, infection and cardiovascular disorders. Thus, it
is necessary to elucidate the pathophysiological role of each PG in various
diseases to develop better therapies with fewer and milder side effects. PGD2 is
a PG that was identified in 1973 by Hamberg and is produced by the activities of
cyclooxygenase and either hematopoietic or lipocalin-type PGD synthase. PGD2
exerts its physiological effects by stimulating two distinct G protein-coupled
receptors, namely D prostanoid receptor (DP) and chemoattractant receptor
homologous molecule expressed on Th2 cells (CRTH2). The physiological role of
PGD2 remains controversial. Some studies have reported that PGD2 has
bronchoconstrictory and pro-inflammatory effects inducing immune cell
accumulation. In contrast, other groups have reported that PGD2 has anti
inflammatory effects by inhibiting the recruitment of dendritic cells and
neutrophils. We have investigated the pathophysiological role of PGD2 using
various disease models and reported on its anti-inflammatory actions. Here, we
review the anti-inflammatory roles of PGD2 and the underlying mechanisms.
PMID- 27498999
TI - Association Between Presence of Virulence Genes and Antibiotic Resistance in
Clinical Klebsiella Pneumoniae Isolates.
AB - OBJECTIVE: To investigate the presence of rmpA and wcaG virulence genes and Class
1, 2, and 3 integrons, and to evaluate a relationship between antibiotic
resistance and virulence in Klebsiella pneumoniae METHODS: We collected a total
of 200 K. pneumoniae isolates from hospitals in Tehran, Iran. Antibiotic
susceptibility was determined using the disk diffusion method. The extended
spectrum beta-lactamase (ESBL) producers were detected using the combination disk
method. We detected the rmpA and wcaG genes and class 1, 2, and 3 integrons via
polymerase chain reaction (PCR). The chi2 test was used for statistical
evaluation. RESULTS: Of 200 isolates, 115 (57.5%) were ESBL producers; 74.0%
carried the class 1 integron, and 1.0% carried the class 2 integron. The gene
rmpA was detected in 7% of isolates and the gene wcaG in 23.5% of isolates.
Integron-positive isolates showed a higher prevalence of wcaG compared with to
integron-negative isolates (P <.05). CONCLUSION: Our results showed a correlation
between presence of virulence gene and antibiotic resistance in K. pneumoniae.
PMID- 27499000
TI - Phosphate and oxygen limitation induce respiratory nitrate reductase 3 synthesis
in stationary-phase mycelium of Streptomyces coelicolor A3(2).
AB - The saprophytic actinobacterium Streptomyces coelicolor A3(2) requires oxygen for
filamentous growth. Surprisingly, the bacterium also synthesizes three active
respiratory nitrate reductases (Nar), which are believed to contribute to
survival, or general fitness, of the bacterium in soil when oxygen becomes
limiting. In this study, we analysed Nar3 and showed that activity of the enzyme
is restricted to stationary-phase mycelium of S. coelicolor. Phosphate limitation
was shown to be necessary for induction of enzyme synthesis. Nar3 synthesis was
inhibited by inclusion of 20 mM phosphate in a defined 'switch assay' in which
highly dispersed mycelium from exponentially growing cultures was shifted to
neutral MOPS-glucose buffer to induce Nar3 synthesis and activity. Quantitative
assessment of nar3 transcripts revealed a 30-fold induction of gene expression in
stationary-phase mycelium. Transcript levels in stationary-phase mycelium
incubated with phosphate were reduced by a little more than twofold, suggesting
that the negative influence of phosphate on Nar3 synthesis was mainly at the post
transcriptional level. Furthermore, it was demonstrated that oxygen limitation
was necessary to induce high levels of Nar3 activity. However, an abrupt shift
from aerobic to anaerobic conditions prevented appearance of Nar3 activity. This
suggests that the bacterium regulates Nar3 synthesis in response to the energy
status of the mycelium. Nitrate had little impact on regulation of the Nar3
level. Together, these data identify Nar3 as a stationary-phase nitrate reductase
in S. coelicolor and demonstrate that enzyme synthesis is induced in response to
both phosphate limitation and hypoxia.
PMID- 27499002
TI - Biallelic ATM alterations detected at diagnosis identify a subset of treatment
naive chronic lymphocytic leukemia patients with reduced overall survival similar
to patients with p53 deletion.
AB - The prognostic impact of biallelic ATM abnormalities (ATM mutation and concurrent
11q deletion) remains unknown. We studied ATM, BIRC3, SF3B1, and NOTCH1 genes in
118 treatment-naive CLL patients at diagnosis. Patients with biallelic ATM
alteration had a similar time to first treatment (TTFT) and shorter overall
survival (OS) compared with patients with isolated 11q deletion and shorter TTFT
and OS when compared to patients with wild-type ATM. Furthermore, biallelic ATM
alteration (HR: 6.4; p <= 0.007) was significantly associated with an increased
risk of death similar to p53 deletion (HR: 6.1; p <= 0.004), superior to 11q
deletion alone (HR: 2.8; p <= 0.022) and independent of other significant
parameters such as age, advanced clinical stage, and complex karyotype. Our
results suggest the identification of ATM mutations in CLL patients with 11q
deletion at diagnosis is clinically relevant and predicts disease progression,
poor response to the treatment, and reduced OS independent of other molecular
prognostic factors.
PMID- 27499003
TI - Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells.
AB - Squamous cell carcinomas (SCCs) are associated with ultraviolet radiation and
multiple genetic changes, but the mechanisms leading to genetic instability are
unclear. SCC cell lines were compared to normal keratinocytes for sensitivity to
ultraviolet radiation, DNA repair kinetics and DNA repair protein expression.
Relative to normal keratinocytes, four SCC cell lines were all variably sensitive
to ultraviolet radiation and, except for the SCC25 cell line, were deficient in
global repair of cyclobutane pyrimidine dimers, although not 6-4 photoproducts.
Impaired DNA repair of cyclobutane pyrimidine dimers was associated with reduced
mRNA expression from XPC but not DDB2 genes which each encode key DNA damage
recognition proteins. However, levels of XPC or DDB2 proteins or both were
variably reduced in repair-deficient SCC cell lines. p53 levels did not correlate
with DNA repair activity or with XPC and DDB2 levels, but p63 levels were
deficient in cell lines with reduced global repair. Repair-proficient SCC25 cells
depleted of p63 lost XPC expression, early global DNA repair activity and UV
resistance. These results demonstrate that some SCC cell lines are deficient in
global nucleotide excision repair and support a role for p63 as a regulator of
nucleotide excision repair in SCCs.
PMID- 27499001
TI - Declining ecosystem health and the dilution effect.
AB - The "dilution effect" implies that where species vary in susceptibility to
infection by a pathogen, higher diversity often leads to lower infection
prevalence in hosts. For directly transmitted pathogens, non-host species may
"dilute" infection directly (1) and indirectly (2). Competitors and predators may
(1) alter host behavior to reduce pathogen transmission or (2) reduce host
density. In a well-studied system, we tested the dilution of the zoonotic Puumala
hantavirus (PUUV) in bank voles (Myodes glareolus) by two competitors and a
predator. Our study was based on long-term PUUV infection data (2003-2013) in
northern Sweden. The field vole (Microtus agrestis) and the common shrew (Sorex
araneus) are bank vole competitors and Tengmalm's owl (Aegolius funereus) is a
main predator of bank voles. Infection probability in bank voles decreased when
common shrew density increased, suggesting that common shrews reduced PUUV
transmission. Field voles suppressed bank vole density in meadows and clear-cuts
and indirectly diluted PUUV infection. Further, Tengmalm's owl decline in 1980
2013 may have contributed to higher PUUV infection rates in bank voles in 2003
2013 compared to 1979-1986. Our study provides further evidence for dilution
effect and suggests that owls may have an important role in reducing disease
risk.
PMID- 27499005
TI - The effect of moisture on the structures and properties of lead halide
perovskites: a first-principles theoretical investigation.
AB - With efficiencies exceeding 20% and low production costs, lead halide perovskite
solar cells (PSCs) have become potential candidates for future commercial
applications. However, there are serious concerns about their long-term stability
and environmental friendliness, heavily related to their commercial viability.
Herein, we present a theoretical investigation based on the ab initio molecular
dynamics (AIMD) simulations and the first-principles density functional theory
(DFT) calculations to investigate the effects of sunlight and moisture on the
structures and properties of MAPbI3 perovskites. AIMD simulations have been
performed to simulate the impact of a few water molecules on the structures of
MAPbI3 surfaces terminated in three different ways. The evolution of geometric
and electronic structures as well as the absorption spectra has been shown. It is
found that the PbI2-terminated surface is the most stable while both the MAI
terminated and PbI2-defective surfaces undergo structural reconstruction, leading
to the formation of hydrated compounds in a humid environment. The moisture
induced weakening of photoabsorption is closely related to the formation of
hydrated species, and the hydrated crystals MAPbI3.H2O and MA4PbI6.2H2O scarcely
absorb the visible light. The electronic excitation in the bare and water
absorbed MAPbI3 nanoparticles tends to weaken Pb-I bonds, especially those around
water molecules, and the maximal decrease of photoexcitation-induced bond order
can reach up to 20% in the excited state in which the water molecules are
involved in the electronic excitation, indicating the accelerated decomposition
of perovskites in the presence of sunlight and moisture. This work is valuable
for understanding the mechanism of chemical or photochemical instability of
MAPbI3 perovskites in the presence of moisture.
PMID- 27499004
TI - Structure of a Highly Active Cephalopod S-crystallin Mutant: New Molecular
Evidence for Evolution from an Active Enzyme into Lens-Refractive Protein.
AB - Crystallins are found widely in animal lenses and have important functions due to
their refractive properties. In the coleoid cephalopods, a lens with a graded
refractive index provides good vision and is required for survival. Cephalopod S
crystallin is thought to have evolved from glutathione S-transferase (GST) with
various homologs differentially expressed in the lens. However, there is no
direct structural information that helps to delineate the mechanisms by which S
crystallin could have evolved. Here we report the structural and biochemical
characterization of novel S-crystallin-glutathione complex. The 2.35-A crystal
structure of a S-crystallin mutant from Octopus vulgaris reveals an active-site
architecture that is different from that of GST. S-crystallin has a preference
for glutathione binding, although almost lost its GST enzymatic activity. We've
also identified four historical mutations that are able to produce a "GST-like" S
crystallin that has regained activity. This protein recapitulates the evolution
of S-crystallin from GST. Protein stability studies suggest that S-crystallin is
stabilized by glutathione binding to prevent its aggregation; this contrasts with
GST-sigma, which do not possess this protection. We suggest that a tradeoff
between enzyme activity and the stability of the lens protein might have been one
of the major driving force behind lens evolution.
PMID- 27499006
TI - Utilization of Feeding Tubes in the Management of Feline Chronic Kidney Disease.
AB - Esophagostomy feeding tubes are useful, and in many cases essential, for the
comprehensive management of cats with moderate to advanced chronic kidney disease
(CKD). They should be considered a lifelong therapeutic appliance to facilitate
the global management of cats with CKD thus providing improved therapeutic
efficacy and quality-of-life. Esophagostomy tubes facilitate the maintenance of
adequate hydration and increase owner compliance by facilitating the
administration of medications. Finally, feeding tubes provide a means to deliver
a stage-appropriate dietary prescription for cats with CKD and maintain an
adequate nutritional plane in a patient that otherwise would be subject to
chronic wasting.
PMID- 27499007
TI - Symmetric Dimethylarginine: Improving the Diagnosis and Staging of Chronic Kidney
Disease in Small Animals.
AB - Chronic kidney disease (CKD) is a common condition in cats and dogs,
traditionally diagnosed after substantial loss of kidney function when serum
creatinine concentrations increase. Symmetric dimethylarginine (SDMA) is a
sensitive circulating kidney biomarker whose concentrations increase earlier than
creatinine as glomerular filtration rate decreases. Unlike creatinine SDMA is
unaffected by lean body mass. The IDEXX SDMA test introduces a clinically
relevant and reliable tool for the diagnosis and management of kidney disease.
SDMA has been provisionally incorporated into the International Renal Interest
Society guidelines for CKD to aid staging and targeted treatment of early and
advanced disease.
PMID- 27499008
TI - Rhizobium favelukesii sp. nov., isolated from the root nodules of alfalfa
(Medicago sativa L).
AB - Strains LPU83T and Or191 of the genus Rhizobium were isolated from the root
nodules of alfalfa, grown in acid soils from Argentina and the USA. These two
strains, which shared the same plasmid pattern, lipopolysaccharide profile,
insertion-sequence fingerprint, 16S rRNA gene sequence and PCR-fingerprinting
pattern, were different from reference strains representing species of the genus
Rhizobium with validly published names. On the basis of previously reported data
and from new DNA-DNA hybridization results, phenotypic characterization and
phylogenetic analyses, strains LPU83T and Or191 can be considered to be
representatives of a novel species of the genus Rhizobium, for which the name
Rhizobium favelukesii sp. nov. is proposed. The type strain of this species is
LPU83T (=CECT 9014T=LMG 29160T), for which an improved draft-genome sequence is
available.
PMID- 27499009
TI - Mitochondrial DNA depletion causes decreased ROS production and resistance to
apoptosis.
AB - Mitochondrial DNA (mtDNA) depletion occurs frequently in many diseases including
cancer. The present study was designed in order to examine the hypothesis that
mtDNA-depleted cells are resistant to apoptosis and to explore the possible
mechanisms responsible for this effect. Parental human osteosarcoma 143B cells
and mtDNA-deficient (Rho or rho) 206 cells (derived from 143B cells) were exposed
to different doses of solar-simulated ultraviolet (UV) radiation. The effects of
solar irradiation on cell morphology were observed under both light and
fluorescence microscopes. Furthermore, apoptosis, mitochondrial membrane
potential (MMP) disruption and reactive oxygen species (ROS) production were
detected and measured by flow cytometry. In both cell lines, apoptosis and ROS
production were clearly increased, whereas MMP was slightly decreased. However,
apoptosis and ROS production were reduced in the Rho206 cells compared with the
143B cells. We also performed western blot analysis and demonstrated the
increased release of cytosolic Cyt c from mitochondria in the 143B cells compared
with that in the Rho206 cells. Thus, we concluded that Rho206 cells exhibit more
resistance to solar-simulated UV radiation-induced apoptosis at certain doses
than 143B cells and this is possibly due to decreased ROS production.
PMID- 27499010
TI - Epigenetic modulation of AR gene expression in prostate cancer DU145 cells with
the combination of sodium butyrate and 5'-Aza-2'-deoxycytidine.
AB - The androgen receptor (AR) plays an essential role in the development and
progression of prostate cancer. Castration-resistant prostate cancer (CRPC) is a
consequence of androgen deprivation therapy. Unchecked CRPC followed by
metastasis is lethal. Some CRPCs show decreased AR gene expression due to
epigenetic mechanisms such as DNA methylation and histone deacetylation. The aim
of this study was to epigenetically modulate the methylated state of the AR gene
leading to targeted demethylation and AR gene expression in androgen-independent
human prostate cancer DU145 cell line, representing the CRPC model with very low
or undetectable AR levels. The cell treatment was based on single and combined
applications of two epigenetic inhibitors, sodium butyrate (NaB) as histone
deacetylases inhibitor and 5'-Aza-2'-deoxycytidine (Aza-dC) as DNA
methyltransferases inhibitor. We found that the Aza-dC in combination with NaB
may help reduce the toxicity of higher NaB concentrations in cancer cells. In
normal RWPE-1 cells and even stronger in cancer DU145 cells, the combined
treatment induced both AR gene expression on the mRNA level and increased histone
H4 acetylation in AR gene promoter. Also activation and maintenance of G2/M cell
cycle arrest and better survival in normal RWPE-1 cells compared to cancer DU145
cells were observed after the treatments. These results imply the selective
toxicity effect of both inhibitors used and their potentially more effective
combined use in the epigenetic therapy of prostate cancer patients.
PMID- 27499011
TI - Corticotropin-Releasing Factor From Rodents to Primates: Translational Hope
Expresses Itself, Pun Intended.
PMID- 27499012
TI - Gain in Translation: Is It Time for Thigmotaxis Studies in Humans?
PMID- 27499014
TI - Twisted Cucurbit[n]urils.
AB - Two new twisted cucurbiturils, cucurbit[13]uril (tQ[13]) and cucurbit[15]uril
(tQ[15]), have been synthesized and separated, and their structures have been
confirmed by NMR spectroscopy and MALDI-TOF mass spectrometry together with the X
ray structures of two new complexes, {Dy(H2O)4Cd(H2O)4tQ[13]}.2.5[CdCl4].65H2O
and {Cd0.5(H2O)2tQ[15]}.[CdCl4].47H2O. tQ[15] is the largest cucurbit[n]uril
(Q[n]) in the Q[n] family reported to date. The X-ray diffraction studies of both
complexes indicated that these large tQ[n]s effectively exhibit two different
cavities-a central cavity and two side cavities. Preliminary host-guest behavior
by each of the new systems was investigated by NMR studies.
PMID- 27499013
TI - ATP-dependent substrate transport by the ABC transporter MsbA is proton-coupled.
AB - ATP-binding cassette transporters mediate the transbilayer movement of a vast
number of substrates in or out of cells in organisms ranging from bacteria to
humans. Current alternating access models for ABC exporters including the
multidrug and Lipid A transporter MsbA from Escherichia coli suggest a role for
nucleotide as the fundamental source of free energy. These models involve cycling
between conformations with inward- and outward-facing substrate-binding sites in
response to engagement and hydrolysis of ATP at the nucleotide-binding domains.
Here we report that MsbA also utilizes another major energy currency in the cell
by coupling substrate transport to a transmembrane electrochemical proton
gradient. The dependence of ATP-dependent transport on proton coupling, and the
stimulation of MsbA-ATPase by the chemical proton gradient highlight the
functional integration of both forms of metabolic energy. These findings
introduce ion coupling as a new parameter in the mechanism of this homodimeric
ABC transporter.
PMID- 27499015
TI - Peridinin, a carotenoid, inhibits proliferation and survival of HTLV-1-infected T
cell lines.
AB - Human T-cell leukemia virus type 1 (HTLV-1) causes either adult T-cell leukemia
(ATL) or chronic inflammatory disorders such as HTLV-1-associated
myelopathy/tropical spastic paraparesis. These diseases are not curable as yet;
therefore new agents for treatment and prevention are needed. Carotenoids are
natural plant compounds with anti-carcinogenic activities. Peridinin is one of
the most abundant carotenoids found in nature. Based on a series of past
experiments, here we investigated the effects of peridinin extracted from
Okinawan coral Isis hippuris on the proliferation and survival of HTLV-1-infected
T-cell lines. The results of water-soluble tetrazolium-8 assay indicated that
peridinin dose-dependently inhibits cell proliferation and viability of HTLV-1
infected T-cell lines. Flow cytometry showed that low concentration of peridinin
induced cell cycle arrest at G1 phase, while higher concentration induced
apoptosis. Peridinin caused cleavage of caspase-3, -8 and -9. Peridinin
significantly reduced the expression of G1 cell cycle regulators, including
cyclin D1, cyclin D2, CDK4, CDK6 and c-Myc, and anti-apoptotic proteins,
including survivin, XIAP and Bcl-2, in a dose-dependent manner. Peridinin
suppressed DNA binding of NF-kappaB. Peridinin inhibited phosphorylation of
IkappaBalpha, RelA, Akt and p70 S6 kinase, and reduced protein expression level
of 3-phosphoinositide-dependent protein kinase 1. Thus, peridinin exerts its anti
proliferative and pro-apoptotic effects by suppressing NF-kappaB and Akt
signaling in HTLV-1-infected T cells. Peridinin also reduced tumor growth in mice
harboring ATL xenograft tumors. The results suggested that peridinin is a
potentially suitable therapeutic agent against HTLV-1-associated diseases.
PMID- 27499016
TI - Editorial (Thematic Selection: Mitochondrial Dysfunction & Neurological
Disorders).
PMID- 27499017
TI - Natural compound oblongifolin C inhibits autophagic flux, and induces apoptosis
and mitochondrial dysfunction in human cholangiocarcinoma QBC939 cells.
AB - The compounds, which are obtained from natural plants or microbes may offer
potential as one of the strategies for the management of cholangiocarcinoma.
Oblongifolin C (OC), a natural small molecule compound extracted and purified
from Garcinia yunnanensis Hu, can activate the mitochondrial apoptotic pathway in
human cervical cancer cells. However, the direct effects of OC on
cholangiocarcinoma cells are not well defined. The effect of OC on cell apoptosis
and its underlying mechanisms were investigated in cultured QBC939 cells by the
methyl thiazol tetrazolium assay, mitochondrial membrane potential, ATP content
and western blot analysis. The present study reported that the in vitro treatment
of human cholangiocarcinoma QBC939 cells with different concentrations (5, 10, 20
and 40 uM) of OC decreased cell viability and induced apoptosis in a dose
dependent manner. The results of the present study also showed that OC-induced
QBC939 cell apoptosis was mediated through the inhibition of autophagy and
mitochondrial dysfunction (MtD). Additionally, inhibiting autophagy increased OC
induced apoptosis and MtD, whereas exposure to the autophagy inducer, rapmycin,
attenuated these changes. Together, the results of the present study are the
first, to the best of our knowledge, to identify OC as a chemotherapeutic agent
against human cholangiocarcinoma QBC939 cells in vitro via the regulation of
autophagy and MtD.
PMID- 27499018
TI - Long-term efficacy and safety results of taliglucerase alfa through 5years in
adult treatment-naive patients with Gaucher disease.
AB - Taliglucerase alfa, the first available plant cell-expressed recombinant
therapeutic protein, is an enzyme replacement therapy approved for Gaucher
disease (GD). PB-06-001, a pivotal phase 3, multicenter, randomized, double
blind, parallel-dose study investigated taliglucerase alfa 30 or 60U/kg every
other week through 9months in treatment-naive adults with GD; 30-month extension
study PB-06-003 followed. Patients completing PB-06-001 and PB-06-003 could
continue treatment in PB-06-007. Nineteen patients enrolled in PB-06-007 (30U/kg,
n=8; 60U/kg, n=9; dose adjusted, n=2); 17 completed 5 total years of treatment.
In these 3 groups, respectively, taliglucerase alfa resulted in mean decreases in
spleen volume (-8.7, -6.9, -12.4 multiples of normal), liver volume (-0.6, -0.4,
0.5 multiples of normal), chitotriosidase activity (-83.1%, -93.4%, -87.9%), and
chemokine (CC motif) ligand 18 concentration (-66.7%, -83.3%, -78.9%), as well as
mean increases in hemoglobin concentration (+2.1, +2.1, +1.8mg/dL) and platelet
count (+31,871, +106,800, +34,000/mm3). The most common adverse events were
nasopharyngitis and arthralgia. Most adverse events were mild/moderate; no
serious adverse events were considered treatment-related. These results
demonstrate continued improvement of disease parameters during 5years of
taliglucerase alfa therapy in 17 treatment-naive patients with no new safety
concerns, extending the taliglucerase alfa clinical efficacy and safety dataset.
This study was registered at www.clinicaltrials.gov as NCT01422187.
PMID- 27499019
TI - Akkermansia glycaniphila sp. nov., an anaerobic mucin-degrading bacterium
isolated from reticulated python faeces.
AB - A Gram-stain-negative, non-motile, strictly anaerobic, oval-shaped, non-spore
forming bacterium (strain PytT) was isolated from reticulated python faeces.
Strain PytT was capable of using mucin as sole carbon, energy and nitrogen
source. Cells could grow singly, in pairs, and were also found to aggregate.
Scanning electron microscopy revealed the presence of filamentous structures
connecting individual bacterial cells. Strain PytT could grow on a limited number
of single sugars, including N-acetylglucosamine, N-acetylgalactosamine, glucose,
lactose and galactose, but only when a plentiful protein source was provided.
Phylogenetic analysis based on 16S rRNA gene sequencing showed strain PytT to
belong to the Verrucomicrobiae class I, family Akkermansiaceae, genus
Akkermansia, with Akkermansia muciniphila MucT as the closest relative (94.4 %
sequence similarity). DNA-DNA hybridization revealed low relatedness of 28.3 %
with A. muciniphila MucT. The G+C content of DNA from strain PytT was 58.2 mol%.
The average nucleotide identity (ANI) of the genome of strain PytT compared to
the genome of strain MucT was 79.7 %. Chemotaxonomic data supported the
affiliation of strain PytT to the genus Akkermansia. Based on phenotypic,
phylogenetic and genetic characteristics, strain PytT represents a novel species
of the genus Akkermansia, for which the name Akkermansia glycaniphila sp. nov. is
proposed. The type strain is PytT (=DSM 100705T=CIP 110913T).
PMID- 27499020
TI - Phosphoproteome Integration Reveals Patient-Specific Networks in Prostate Cancer.
AB - We used clinical tissue from lethal metastatic castration-resistant prostate
cancer (CRPC) patients obtained at rapid autopsy to evaluate diverse genomic,
transcriptomic, and phosphoproteomic datasets for pathway analysis. Using Tied
Diffusion through Interacting Events (TieDIE), we integrated differentially
expressed master transcriptional regulators, functionally mutated genes, and
differentially activated kinases in CRPC tissues to synthesize a robust signaling
network consisting of druggable kinase pathways. Using MSigDB hallmark gene sets,
six major signaling pathways with phosphorylation of several key residues were
significantly enriched in CRPC tumors after incorporation of phosphoproteomic
data. Individual autopsy profiles developed using these hallmarks revealed
clinically relevant pathway information potentially suitable for patient
stratification and targeted therapies in late stage prostate cancer. Here, we
describe phosphorylation-based cancer hallmarks using integrated personalized
signatures (pCHIPS) that shed light on the diversity of activated signaling
pathways in metastatic CRPC while providing an integrative, pathway-based
reference for drug prioritization in individual patients.
PMID- 27499021
TI - GPCR-G Protein-beta-Arrestin Super-Complex Mediates Sustained G Protein
Signaling.
AB - Classically, G protein-coupled receptor (GPCR) stimulation promotes G protein
signaling at the plasma membrane, followed by rapid beta-arrestin-mediated
desensitization and receptor internalization into endosomes. However, it has been
demonstrated that some GPCRs activate G proteins from within internalized
cellular compartments, resulting in sustained signaling. We have used a variety
of biochemical, biophysical, and cell-based methods to demonstrate the existence,
functionality, and architecture of internalized receptor complexes composed of a
single GPCR, beta-arrestin, and G protein. These super-complexes or "megaplexes"
more readily form at receptors that interact strongly with beta-arrestins via a C
terminal tail containing clusters of serine/threonine phosphorylation sites.
Single-particle electron microscopy analysis of negative-stained purified
megaplexes reveals that a single receptor simultaneously binds through its core
region with G protein and through its phosphorylated C-terminal tail with beta
arrestin. The formation of such megaplexes provides a potential physical basis
for the newly appreciated sustained G protein signaling from internalized GPCRs.
PMID- 27499022
TI - Glycosylation-Dependent IFN-gammaR Partitioning in Lipid and Actin Nanodomains Is
Critical for JAK Activation.
AB - Understanding how membrane nanoscale organization controls transmembrane
receptors signaling activity remains a challenge. We studied interferon-gamma
receptor (IFN-gammaR) signaling in fibroblasts from homozygous patients with a
T168N mutation in IFNGR2. By adding a neo-N-glycan on IFN-gammaR2 subunit, this
mutation blocks IFN-gamma activity by unknown mechanisms. We show that the
lateral diffusion of IFN-gammaR2 is confined by sphingolipid/cholesterol
nanodomains. In contrast, the IFN-gammaR2 T168N mutant diffusion is confined by
distinct actin nanodomains where conformational changes required for Janus
activated tyrosine kinase/signal transducer and activator of transcription
(JAK/STAT) activation by IFN-gamma could not occur. Removing IFN-gammaR2 T168N
bound galectins restored lateral diffusion in lipid nanodomains and JAK/STAT
signaling in patient cells, whereas adding galectins impaired these processes in
control cells. These experiments prove the critical role of dynamic receptor
interactions with actin and lipid nanodomains and reveal a new function for
receptor glycosylation and galectins. Our study establishes the physiological
relevance of membrane nanodomains in the control of transmembrane receptor
signaling in vivo. VIDEO ABSTRACT.
PMID- 27499023
TI - Memory of Inflammation in Regulatory T Cells.
AB - Eukaryotic cells can "remember" transient encounters with a wide range of
stimuli, inducing lasting states of altered responsiveness. Regulatory T (Treg)
cells are a specialized lineage of suppressive CD4 T cells that act as critical
negative regulators of inflammation in various biological contexts. Treg cells
exposed to inflammatory conditions acquire strongly enhanced suppressive
function. Using inducible genetic tracing, we analyzed the long-term stability of
activation-induced transcriptional, epigenomic, and functional changes in Treg
cells. We found that the inflammation-experienced Treg cell population reversed
many activation-induced changes and lost its enhanced suppressive function over
time. The "memory-less" potentiation of Treg suppressor function may help avoid a
state of generalized immunosuppression that could otherwise result from repeated
activation.
PMID- 27499024
TI - A case of recurrent fever in an older man caused by Coxiella burnetii.
AB - Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii.
While it is mostly an asymptomatic infection, acute disease can manifest as fever
associated with signs of pneumonia or hepatitis. Chronic Q fever develops in 1-5%
of infected persons. Patients with a history of cardiac valve surgery, vascular
prosthesis or vascular aneurysm, and to a lesser extent patients with pre
existing valvular disease, immune deficiencies, or renal insufficiency, are at
highest risk. Most common manifestations are Q fever endocarditis and Q fever
vascular infection. We present a case of chronic Q fever, followed by a summary
of available literature.
PMID- 27499026
TI - Quantum Chemistry on Quantum Computers: A Polynomial-Time Quantum Algorithm for
Constructing the Wave Functions of Open-Shell Molecules.
AB - Quantum computers are capable to efficiently perform full configuration
interaction (FCI) calculations of atoms and molecules by using the quantum phase
estimation (QPE) algorithm. Because the success probability of the QPE depends on
the overlap between approximate and exact wave functions, efficient methods to
prepare accurate initial guess wave functions enough to have sufficiently large
overlap with the exact ones are highly desired. Here, we propose a quantum
algorithm to construct the wave function consisting of one configuration state
function, which is suitable for the initial guess wave function in QPE-based FCI
calculations of open-shell molecules, based on the addition theorem of angular
momentum. The proposed quantum algorithm enables us to prepare the wave function
consisting of an exponential number of Slater determinants only by a polynomial
number of quantum operations.
PMID- 27499025
TI - A subpopulation of high IL-21-producing CD4(+) T cells in Peyer's Patches is
induced by the microbiota and regulates germinal centers.
AB - The production of IL-21 by T follicular helper (Tfh) cells is vital in driving
the germinal centre reaction and high affinity antibody formation. However, the
degree of Tfh cell heterogeneity and function is not fully understood. We used a
novel IL-21eGFP reporter mouse strain to analyze the diversity and role of Tfh
cells. Through the analysis of GFP expression in lymphoid organs of IL-21eGFP
mice, we identified a subpopulation of GFP(+), high IL-21 producing Tfh cells
present only in Peyer's Patches. GFP(+)Tfh cells were found to be polyclonal and
related to GFP(-)Tfh cells of Peyer's Patches in TCR repertoire composition and
overall gene expression. Studies on the mechanisms of induction of GFP(+)Tfh
cells demonstrated that they required the intestinal microbiota and a diverse
repertoire of CD4(+) T cells and B cells. Importantly, ablation of GFP(+) cells
resulted in a reduced frequency of Peyer's Patches IgG1 and germinal center B
cells in addition to small but significant shifts in gut microbiome composition.
Our work highlights the diversity among IL-21 producing CD4(+) Tfh cells, and the
interrelationship between the intestinal bacteria and Tfh cell responses in the
gut.
PMID- 27499027
TI - Human Cytomegalovirus Increases the Risk of Future Hemorrhagic But Not Ischemic
Stroke - A Nested Case-Control Study.
AB - BACKGROUND: The cause-and-effect relationship between human cytomegalovirus
(HCMV) and stroke has not been widely elucidated. We aimed to determine if HCMV
infection has an increased risk of future stroke in hypertensive patients in
rural areas of China. METHODS AND RESULTS: This was a nested case-control study
from a prospective cohort study. A total of 300 newly diagnosed stroke cases with
a median follow-up period of 8.4 years and 300 matched controls were selected for
the present analysis. Adjusted odds ratio (OR) for stroke associated with HCMV
DNA seropositivity was calculated by conditional logistic regression. HCMV DNA
was detected in 38 of 300 samples from stroke patients and in 17 of 300 control
samples (12.7% vs. 5.7%; P=0.023). Seropositivity for HCMV DNA increased the risk
of incident stroke (unadjusted OR, 1.437; 95% confidence interval (CI), 1.023
2.020, P=0.037) and adjustment for other potential cardiovascular confounders
only slightly changed the OR (1.464; 95% CI, 1.003-2.137, P=0.048). After
controlling for potential cardiovascular confounders, the OR for hemorrhagic
stroke associated with HCMV DNA was 1.718 (95% CI, 1.042-2.832), whereas the OR
for ischemic stroke was 0.450 (95% CI, 0.142-1.428). CONCLUSIONS: Seropositivity
for HCMV DNA was positively associated with total and hemorrhagic but not
ischemic stroke, which persisted after controlling for other cardiovascular
factors. (Circ J 2016; 80: 2235-2239).
PMID- 27499028
TI - Do systemic antibiotics prevent dry socket and infection after third molar
extraction? A systematic review and meta-analysis.
AB - OBJECTIVES: The use of antibiotics to prevent dry socket and infection is a
controversial but widespread practice. The aim of the study is to assess the
efficacy of systemic antibiotics in reducing the frequencies of these
complications after extraction. STUDY DESIGN: A systematic review and meta
analysis, according to the PRISMA statement, based on randomized double-blind
placebo-controlled trials evaluating systemic antibiotics to prevent dry socket
and infection after third molar surgery. Databases were searched up to June 2015.
Relative risks (RRs) were calculated with inverse variance-weighted, fixed
effect, or random-effect models. RESULTS: We included 22 papers in the
qualitative and 21 in the quantitative review (3304 extractions). Overall-RR was
0.43 (95% confidence interval [CI] 0.33-0.56; P < .0001); number needed to treat,
14 (95% CI 11-19). Penicillins-RR: 0.40 (95% CI 0.27-0.59). Nitroimidazoles-RR:
0.56 (95% CI 0.38-0.82). No serious adverse events were reported. CONCLUSIONS:
Systemic antibiotics significantly reduce the risk of dry socket and infection in
third molar extraction.
PMID- 27499029
TI - Development and psychometric properties of a health knowledge test on six chronic
conditions.
AB - OBJECTIVES: The aim of this study was to develop and test the psychometric
properties of a health knowledge test on common chronic conditions in the general
population. METHODS: Operationalization based on a facet design led to 108
knowledge items on six conditions: cardiovascular disease, cancer, respiratory
diseases, musculoskeletal system conditions, depression, and chronic pain. We
refined the items (qualitative study 1; N=20) and selected the items by applying
a mixed Rasch model (study 2; N=861). The psychometric properties (Study 3;
N=4144) of the remaining 24 items were tested using exploratory (split sample
N=2110) and confirmatory factor analyses (split sample N=2034). RESULTS: 108
items were refined within study 1, 24 of which were selected in study 2. In study
3, a general health knowledge factor was confirmed based on six subscales on
specific conditions. Convergent validity was confirmed by the overlap of health
knowledge with education and perceived health knowledge. CONCLUSION: The
development and evaluation of the psychometric properties of a health knowledge
test on six common conditions will improve future research on health knowledge.
PRACTICAL IMPLICATIONS: Chronic conditions present a challenge; assessing the
level of health knowledge is the first step to prevent and to cope with these
conditions.
PMID- 27499030
TI - Treatment effect expressed as the novel Delay of Event measure is associated with
high willingness to initiate preventive treatment - A randomized survey
experiment comparing effect measures.
AB - OBJECTIVES: This study aimed to investigate patients' willingness to initiate a
preventive treatment and compared two established effect measures to the newly
developed Delay of Events (DoE) measure that expresses treatment effect as a gain
in event-free time. METHODS: In this cross-sectional, randomized survey
experiment in the general Swedish population,1079 respondents (response rate
60.9%) were asked to consider a preventive cardiovascular treatment. Respondents
were randomly allocated to one of three effect descriptions: DoE, relative risk
reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate
analyses were performed investigating willingness to initiate treatment, views on
treatment benefit, motivation and importance to adhere and willingness to pay for
treatment. RESULTS: Eighty-one percent were willing to take the medication when
the effect was described as DoE, 83.0% when it was described as RRR and 62.8%
when it was described as ARR. DoE and RRR was further associated with positive
views on treatment benefit, motivation, importance to adhere and WTP.
CONCLUSIONS: Presenting treatment effect as DoE or RRR was associated with a high
willingness to initiate treatment. PRACTICE IMPLICATIONS: An approach based on
the novel time-based measure DoE may be of value in clinical communication and
shared decision making.
PMID- 27499031
TI - Red emission fluorescent probes for visualization of monoamine oxidase in living
cells.
AB - Here we report two novel red emission fluorescent probes for the highly sensitive
and selective detection of monoamine oxidase (MAO) with large Stokes shift (227
nm). Both of the probes possess solid state fluorescence and can accomplish the
identification of MAO on test papers. The probe MAO-Red-1 exhibited a detection
limit down to 1.2 MUg mL(-1) towards MAO-B. Moreover, the cleavage product was
unequivocally conformedby HPLC and LCMS and the result was in accordance with the
proposed oxidative deamination mechanism. The excellent photostability of MAO-Red
1 was proved both in vitro and in vivo through fluorescent kinetic experiment and
laser exposure experiment of confocal microscopy, respectively. Intracellular
experiments also confirmed the low cytotoxity and exceptional cell imaging
abilities of MAO-Red-1. It was validated both in HeLa and HepG2 cells that MAO
Red-1 was capable of reporting MAO activity through the variation of fluorescence
intensity.
PMID- 27499032
TI - Requirement of HDAC6 for activation of Notch1 by TGF-beta1.
AB - TGF-beta1 is enriched in the tumor microenvironment and acts as a key inducer of
epithelial to mesenchymal transition (EMT) in lung cancer. The NOTCH signaling
pathway is conserved across species and is an essential pathway for development,
cell differentiation, and cancer biology. Dysregulation of Notch signaling is a
common feature of non-small cell lung cancer (NSCLC) and is correlated with poor
prognosis. Crosstalk exists between the NOTCH and TGF-beta signaling pathways in
EMT. Herein we report that histone deacetylase 6 (HDAC6) modulates TGF-beta1
mediated activation of the Notch pathway. HDAC6, a primarily cytoplasmic
deacetylase, mediates TGF-beta1-induced EMT in human lung cancer cells.
Inhibition of HDAC6 with a small molecule inhibitor, namely tubacin or with siRNA
attenuated TGF-beta1-induced Notch-1 signaling. We show that TGFbeta-1-induced
EMT is accompanied by rapid HDAC6-dependent deacetylation of heat shock protein
90 (HSP90). Consistently, inhibition of HSP90 with its small molecule inhibitor
17AAG attenuated expression of TGF-beta1-induced Notch-1 target genes, HEY-1 and
HES-1. These findings reveal a novel function of HDAC6 in EMT via mediating the
TGF-beta-Notch signaling cascade, and support HDAC6 as a key regulator of TGFbeta
induced EMT in NSCLC. This work suggests that HDAC6 may be an attractive
therapeutic target against tumor progression and metastasis.
PMID- 27499033
TI - Oscillatory Characteristics of the Vocal Folds Across the Tenor Passaggio.
AB - INTRODUCTION: Recent research has revealed that classically trained tenors tend
to constrict epilaryngeal structures when singing in and above the passaggio (ie,
the frequency region where register events typically occur). These constrictions
complicate visibility of vocal fold oscillatory patterns with transoral rigid
high-speed video endoscopy, thus limiting the current understanding of laryngeal
dynamics in the passaggio region of tenors. MATERIALS AND METHODS: This
investigation analyzed seven professionally trained western classical tenors
using high-speed digital imaging (HSDI) at 20,000 frames per second via
transnasal flexible endoscopy. The participants produced transitions (a) from
modal to falsetto register and (b) from modal to stage voice above the passaggio
(SVaP) during ascending pitch glides from A3 (220 Hz) to A4 (440 Hz) on vowel
/i/. HSDI data were complemented by simultaneous acoustic and
electroglottographic recordings. RESULTS: For many subjects both transition types
were associated with constrictions of the epilaryngeal structures during the
pitch glide. These constrictions appeared to be more distinct for the SVaP than
for falsetto. No major irregularities of vocal fold oscillations in the sense of
fundamental frequency jumps were observed for either transition type. However,
during the transitions, the open quotient derived from the glottal area waveform
(OQGAW) increased; in falsetto, the OQGAW was greater and the
electroglottographic cepstral peak prominence was lower than in SVaP.
CONCLUSIONS: Epilaryngeal constrictions should be considered typical for tenors
singing at high fundamental frequencies. Vocal fold oscillatory patterns are
changing not only for the register shift from modal to falsetto but also for the
transition from modal to SVaP, indicating a need for laryngeal adjustments during
these transitions.
PMID- 27499034
TI - Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the
Akt/NF-kappaB pathway in CD133-positive osteosarcoma MG-63 cells.
AB - The development of chemoresistance is closely linked to the plateau of the
survival rate in osteosarcoma (OS) patients. CD133-positive (CD133+) OS cells are
known as cancer stem cells (CSCs) in OS and exhibit the characteristic of
chemoresistance. In this study, CD133+ and CD133-negative (CD133-) MG-63 cells
were isolated by magnetic activated cell sorting (MACS). We verified that CD133+
MG-63 cells were more resistant to cisplatin (CDDP) than CD133- MG-63 cells. DNA
dependent protein kinase catalytic subunit (DNA-PKcs) and P-glycoprotein (P-gp)
were expressed at higher levels in the CD133+ MG-63 cells compared with those
levels in the CD133- MG-63 cells, whereas downregulation of DNA-PKcs by small
interfering RNA (siRNA) decreased chemoresistance to CDDP and P-gp expression at
the mRNA and protein levels in these cells. This indicated that DNA-PKcs was
correlated with P-gp expression in the CD133+ MG-63 cells. The Akt/NF-kappaB
pathway was hyperactivated in the CD133+ MG-63 cells, whereas inhibition of the
Akt/NF-kappaB pathway downregulated P-gp expression. In addition, downregulation
of DNA-PKcs suppressed the activity of the Akt/NF-kappaB pathway. These results
revealed that downregulation of DNA-PKcs could decrease P-gp expression via
suppression of the Akt/NF-kappaB pathway in CD133+ MG-63 cells. Therefore,
inhibition of DNA-PKcs decreases P-gp expression and sensitizes OS CSCs to
chemotherapeutic agents in vitro, which needs to be further validated in vivo.
PMID- 27499035
TI - An 'Omics' Perspective on Cardiomyopathies and Heart Failure.
AB - Pathological enlargement of the heart, represented by hypertrophic cardiomyopathy
(HCM) and dilated cardiomyopathy (DCM), occurs in response to many genetic and
non-genetic factors. The clinical course of cardiac hypertrophy is remarkably
variable, ranging from lifelong absence of symptoms to rapidly declining heart
function and sudden cardiac death (SCD). Unbiased omics studies have begun to
provide a glimpse into the molecular framework underpinning altered
mechanotransduction, mitochondrial energetics, oxidative stress, and
extracellular matrix in the heart undergoing physiological and pathological
hypertrophy. Omics analyses indicate that post-transcriptional regulation of gene
expression plays an overriding role in the normal and diseased heart. Studies to
date highlight a need for more effective bioinformatics to better integrate
patient omics data with their comprehensive clinical histories.
PMID- 27499036
TI - Increased expression levels of ppGalNAc-T13 in lung cancers: Significance in the
prognostic diagnosis.
AB - ppGalNAc-T13 is upregulated along with reduced expression of GM1 in high
metastatic sublines of the murine Lewis lung cancer cell line, but little is
known about the implication of ppGalNAc-T13 expression in human cancers. Since
lung cancer cell lines showed high expression levels of ppGalNAc-T13, we analyzed
ppGalNAc-T13 expression in surgical lung cancer specimens to examine whether
ppGalNAc-T13 can be used as a prognostic marker or a therapeutic target. We
analyzed mRNA expression levels of GALNT13 and its variant exon usages in
surgical specimens by real-time RT-PCR, and the results were evaluated by
correlating with clinical data. Ninety-one surgical specimens were analyzed.
Consequently, recurrence-free survival was significantly shorter (P=0.045) in
high expression group of GALNT13 mRNA. In the analysis of tumor specific exon
usage in GALNT13 RNA sequence, one variant exon was significantly associated with
worse prognosis. By contrast, in another variant exon, positive variant
expression group showed better prognosis than negative group. We also tried to
detect GALNT13 mRNA in 63 serum samples from patients with lung cancers to
examine whether GALNT13 mRNA can be measured in body fluids, detecting
significant levels in 4 samples. Finally, expression of GM1, ppGalNAc-T13 and
trimeric Tn antigen was examined by immunohistochemistry in order to evaluate
them as a prognostic factor. It was demonstrated that ppGalNAc-T13 and trimeric
Tn antigen had a relationship with worse prognosis in 35 investigated lung cancer
patients. In conclusion, our results suggest that ppGalNAc-T13 might be a useful
prognostic factor of lung cancers.
PMID- 27499037
TI - Deficiency of 53BP1 inhibits the radiosensitivity of colorectal cancer.
AB - The present study aimed to observe the influence of p53 binding protein 1 (53BP1)
silencing on the radiosensitivity of colorectal cancer (CRC) cells and
investigated the potential underlying mechanisms. The differences in
radiosensitivity among four CRC cells were detected by the clone formation assay,
while the expression of their 53BP1 was detected by the western blot analysis.
HCT116 cells with relatively high expression of 53BP1 were selected to silence
the expression of 53BP1 by shRNA intervention. The influence on proliferation,
apoptosis, and cell cycle distribution was detected by immunofluorescent staining
of Ki-67 and flow cytometry. The expression of relevant proteins in the apoptotic
pathway ATM-CHK2-p53 was further analyzed by western blot analysis. The
expression of 53BP1 was found to be closely related to the radiosensitivity of
the CRC cells. Decreased expression of 53BP1 led to the tolerance of HCT116 cells
to radiation. The detection of tumor proliferation, apoptosis, and cell cycle
showed that decreased expression of 53BP1 resulted in an increased S-phase
percentage of HCT116 cells, an increased proliferating rate, and a decreased
apoptotic rate after radiation. The analysis of the molecular pathway showed that
the reduced expression of 53BP1 decreased the protein expression of ATM, CHK2,
and the phosphorylated products associated with the p53 apoptotic pathway. In
conclusion, decreased expression of 53BP1 leads to radiotolerance of CRC cells,
and the underlying mechanism is probably related to the decreased expression of
relevant proteins in the ATM-CHK2-p53 pathway, which affects cell cycle,
apoptosis and proliferation.
PMID- 27499038
TI - Insights into the percutaneous penetration of antidiabetic agents.
AB - It has been suggested that destruction of beta cells through apoptosis leads to
type 1 diabetes (T1DM) while type 2 diabetes (T2DM) is caused mainly by increased
insulin resistance. Several therapeutic agents are available for the management
of diabetes. While researchers continue to investigate disease-modifying
compounds, it is also important to develop alternative drug delivery systems for
existing medications with the goal of modulating bioavailability and/or
pharmacokinetic half-life. Transdermal drug delivery offers a number of
advantages including improved compliance, lack of gastric irritation and the
possibility of altering bioavailability and and/or half-life. In this review, the
percutaneous penetration of antidiabetic agents is discussed. This is
particularly significant given the fact that several compounds with hypoglycemic
properties are being developed by academic research laboratories and the
biotechnological industry. Microneedles, sonophoresis, chemical penetration
enhancers and iontophoresis are some of the approaches used for the transdermal
delivery of antidiabetic agents. It is anticipated that with more research, some
of these transdermal drug delivery systems will be incorporated into clinical
practice.
PMID- 27499039
TI - The role of a small-scale cutoff in determining molecular layers at fluid
interfaces.
AB - The existence of molecular layers at liquid/vapour interfaces has been a long
debated issue. More than ten years ago it was shown, using computer simulations,
that correlations at the liquid/vapour interface resemble those of bulk liquids,
even though they can be detected in experiments only in a few cases, where they
are so strong that they cannot be concealed by the geometrical smearing of
capillary fluctuations. The results of the intrinsic analysis techniques used in
computer experiments, however, are still often questioned because of their
dependence on a free parameter that usually represents a small-scale cutoff used
to determine the interface. In this work I show that there is only one value of
the cutoff that can ensure a quantitative explanation of the intrinsic density
correlation peaks in terms of successive layer contributions. The value of the
cutoff coincides, with a high accuracy, with the molecular diameter.
PMID- 27499040
TI - Reply: Evolutionary approach sheds light on the significance of vascular
calcification.
PMID- 27499041
TI - Editorial commentary: Fractional flow reserve-A diagnostic tool, a prognostic
index.
PMID- 27499042
TI - Distinct interacting core taxa in co-occurrence networks enable discrimination of
polymicrobial oral diseases with similar symptoms.
AB - Polymicrobial diseases, which can be life threatening, are caused by the presence
and interactions of multiple microbes. Peri-implantitis and periodontitis are
representative polymicrobial diseases that show similar clinical symptoms. To
establish a means of differentiating between them, we compared microbial species
and functional genes in situ by performing metatranscriptomic analyses of peri
implantitis and periodontitis samples obtained from the same subjects (n = 12
each). Although the two diseases differed in terms of 16S rRNA-based taxonomic
profiles, they showed similarities with respect to functional genes and taxonomic
and virulence factor mRNA profiles. The latter-defined as microbial virulence
types-differed from those of healthy periodontal sites. We also showed that
networks based on co-occurrence relationships of taxonomic mRNA abundance (co
occurrence networks) were dissimilar between the two diseases. Remarkably, these
networks consisted mainly of taxa with a high relative mRNA-to-rRNA ratio, with
some showing significant co-occurrence defined as interacting core taxa,
highlighting differences between the two groups. Thus, peri-implantitis and
periodontitis have shared as well as distinct microbiological characteristics.
Our findings provide insight into microbial interactions in polymicrobial
diseases with unknown etiologies.
PMID- 27499043
TI - Selection and characterization of the novel anti-human PD-1 FV78 antibody from a
targeted epitope mammalian cell-displayed antibody library.
AB - Currently, display-based methods are well established and widely used in antibody
engineering for affinity maturation and structural stability improvement. We
obtained a novel anti-human programmed death 1 (PD-1) antibody using computer
aided design and a mammalian cell display technology platform. We used computer
aided modeling and distance geometry methods to predict and assign the key
residues that contributed to the binding of human PD-L1 to PD-1. Then, we
analyzed the sequence of nivolumab (an anti-human PD-1 antibody, referred to as
MIL75 in the article) to determine the template for antibody design and library
construction. We identified a series of potential substitutions on the obtained
template and constructed a virtual epitope-targeted antibody library based on the
physicochemical properties and each possible location of the assigned key
residues. The virtual antibody libraries were displayed on the surface of
mammalian cells as the antigen-binding fragments of full-length immunoglobulin G.
Then, we used flow cytometry and sequencing approaches to sort and screen the
candidates. Finally, we obtained a novel anti-human PD-1 antibody named FV78.
FV78 competitively recognized the PD-1 epitopes that interacted with MIL75 and
possessed an affinity comparable to MIL75. Our results implied that FV78
possessed equivalent bioactivity in vitro and in vivo compared with MIL75, which
highlighted the probability and prospect of FV78 becoming a new potential
antibody therapy.
PMID- 27499045
TI - Corrigendum to 'Externalizing behaviors of Ukrainian children: The role of
parenting' [Child Abuse Negl. 54 (2016) 23-32].
PMID- 27499044
TI - CD5 expression promotes IL-10 production through activation of the MAPK/Erk
pathway and upregulation of TRPC1 channels in B lymphocytes.
AB - CD5 is constitutively expressed on T cells and a subset of mature normal and
leukemic B cells in patients with chronic lymphocytic leukemia (CLL). Important
functional properties are associated with CD5 expression in B cells, including
signal transducer and activator of transcription 3 activation, IL-10 production
and the promotion of B-lymphocyte survival and transformation. However, the
pathway(s) by which CD5 influences the biology of B cells and its dependence on B
cell receptor (BCR) co-signaling remain unknown. In this study, we show that CD5
expression activates a number of important signaling pathways, including Erk1/2,
leading to IL-10 production through a novel pathway independent of BCR
engagement. This pathway is dependent on extracellular calcium (Ca2+) entry
facilitated by upregulation of the transient receptor potential channel 1 (TRPC1)
protein. We also show that Erk1/2 activation in a subgroup of CLL patients is
associated with TRPC1 overexpression. In this subgroup of CLL patients, small
inhibitory RNA (siRNA) for CD5 reduces TRPC1 expression. Furthermore, siRNAs for
CD5 or for TRPC1 inhibit IL-10 production. These findings provide new insights
into the role of CD5 in B-cell biology in health and disease and could pave the
way for new treatment strategies for patients with B-CLL.
PMID- 27499047
TI - Selectivity in Small Molecule Splicing Modulation.
AB - The dysregulation of RNA splicing is a molecular hallmark of disease, including
different and often complex cancers. While gaining recognition as a target for
therapeutic discovery, understanding the complex mechanisms guiding RNA splicing
remains a challenge for chemical biology. The discovery of small molecule
splicing modulators has recently enabled an evaluation of the mechanisms of
aberrant splicing. We now report on three unique features within the selectivity
of splicing modulators. First, we provide evidence that structural modifications
within a splicing modulator can alter the splicing of introns in specific genes
differently. These studies indicate that structure activity relationships not
only have an effect on splicing activity but also include specificity for
specific introns within different genes. Second, we find that these splicing
modulators also target the mRNAs encoding components of the spliceosome itself.
Remarkably, this effect includes the genes for the SF3B complex, a target of
pladienolide B and related splicing modulators. Finally, we report on the first
observation of a temporal phenomenon associated with small molecule splicing
modulation. Combined, these three observations provide an important new
perspective for the exploration of splicing modulation in terms of both future
medicinal chemistry programs as well as understanding the key facets underlying
its timing.
PMID- 27499046
TI - Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G
protein subunit Galphai2.
AB - Putative functions of the heterotrimeric G-protein subunit Galphai2-dependent
signaling include ion channel regulation, cell differentiation, proliferation and
apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo
eryptosis, characterized by cell shrinkage and cell membrane scrambling with
phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased
cytosolic Ca(2+) activity and ceramide. In the present study, we show that
Galphai2 is expressed in both murine and human erythrocytes and further examined
the survival of erythrocytes drawn from Galphai2-deficient mice (Galphai2(-/-))
and corresponding wild-type mice (Galphai2(+/+)). Our data show that plasma
erythropoietin levels, erythrocyte maturation markers, erythrocyte counts,
hematocrit and hemoglobin concentration were similar in Galphai2(-/-) and
Galphai2(+/+) mice but the mean corpuscular volume was significantly larger in
Galphai2(-/-) mice. Spontaneous PS exposure of circulating Galphai2(-/-)
erythrocytes was significantly lower than that of circulating Galphai2(+/+)
erythrocytes. PS exposure was significantly lower in Galphai2(-/-) than in
Galphai2(+/+) erythrocytes following ex vivo exposure to hyperosmotic shock,
bacterial sphingomyelinase or C6 ceramide. Erythrocyte Galphai2 deficiency
further attenuated hyperosmotic shock-induced increase of cytosolic Ca(2+)
activity and cell shrinkage. Moreover, Galphai2(-/-) erythrocytes were more
resistant to osmosensitive hemolysis as compared to Galphai2(+/+) erythrocytes.
In conclusion, Galphai2 deficiency in erythrocytes confers partial protection
against suicidal cell death.
PMID- 27499048
TI - Challenges in detecting disease modification in Parkinson's disease clinical
trials.
AB - Despite the wealth of encouraging data from numerous compounds that demonstrate
"neuroprotection" in pre-clinical studies of Parkinson's disease, and despite
numerous clinical trials, to date, no intervention has been demonstrated to able
to modify the course of disease progression. While this "failure to translate" is
likely due to numerous factors including our incomplete understanding of the
pathogenic mechanisms underlying PD together with excessive reliance on data from
the toxin-based animal models of PD, here we will discuss the "structural issues"
pertaining to inadequate clinical trial design, selection of inappropriate
endpoints and poor patient selection which are often not addressed following
failed disease modification trials. Future directions to overcome these
challenges such as reducing the heterogeneity of patient cohorts, identifying and
utilising a pre-diagnostic population, embracing a personalised medicine approach
and utilising novel trial designs may be required to ultimately fulfil the goal
of conclusively demonstrating evidence of disease modification.
PMID- 27499049
TI - Task specific dystonia in a juggler.
PMID- 27499050
TI - High mobility group box 1 and tumor growth factor beta: useful biomarkers in
pediatric patients receiving peritoneal dialysis.
AB - BACKGROUND: Peritonitis, the most important limitation of peritoneal dialysis
(PD), could be detected by biomarkers in dialysate effluent, representing a
noninvasive method to indirectly assess the peritoneum status. The aim of our
study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating
its role as precocious marker of peritoneum damage during peritonitis.
Transforming growth factor (TGF)-beta was correlated with peritoneal transport
characteristics. METHODS: Six patients, treated by ambulatory PD, were enrolled.
Samples were collected at the onset of peritonitis (T1) and every day until its
resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was
also evaluated. Peritoneal Equilibration Test evaluated the filter activity of
peritoneum. RESULTS: In patients with acute peritonitis, the highest serum and
peritoneal HMGB1 values (64 +/- 3.6 and 70 +/- 5.3 ng/mL, respectively) were
assessed, with a progressive decrease of their levels at the resolution time (T
end: sHMGB1:36 +/- 2.5; pHMGB1:30.5 +/- 7.0 ng/mL). While no differences of sWBC
and pWBC were observed between baseline and T-end values, pHMGB1 levels remained
higher at T-end than those observed at T0 (pHMGB1:30.5 +/- 7.0 versus 6.9 +/-
3.6; p < 0.0001). TGF-beta levels were higher in patients with low peritoneal
permeability than in medium or high transporter patients (81 +/- 15.5 versus 24.3
+/- 7.5 pg/mL; p = 0.01). An inverse correlation was found between TGF-beta
levels and dialysate/plasmatic creatinine values (r = -0.83; p = 0.03).
CONCLUSION: HMGB1 represents a useful biomarker for peritoneum evaluation in PD
patients. A prognostic role of this alarmin, as a marker of response to therapy,
could be hypothesized. TGF-beta could predict the peritoneal transport status and
dialysis technique adequacy.
PMID- 27499051
TI - The nomenclatural type of the genus Methanocorpusculum Zellner et al. 1988 and
the selection of the correct name.
AB - A recent Request for an Opinion has raised the issue of the inter-relationship
between Methanocorpusculum parvum Zellner et al. 1988, the type species of the
genus Methanocorpusculum Zellner et al. 1988 as defined at the time of valid
publication of the genus name and the subsequent recognition of
Methanocorpusculum aggregans (Ollivier et al., 1985) Xun et al.1989 as an earlier
heterotypic synonym. Examination of the relevant literature indicates that there
are a number of misunderstandings that have arisen. In particular
misinterpretation of Rule 15 of the International Code of Nomenclature of
Prokaryotes continues to be a source of confusion. Additional problems centre on
whether the nomenclatural type of a taxon continues to be the nomenclatural type
even if that name is not treated as the correct name and would not appear in a
list of names in a given classification. It would be appropriate to clarify these
issues.
PMID- 27499052
TI - A shared N-terminal hydrophobic tail for the formation of nanoparticulates.
AB - AIM: Nanoparticulate design is important for the production of nanotechnological
materials and passive immunogens. Using lessons from our hepatitis E vaccine, we
herein design protein-based nanoparticles through incorporation of an N-terminal
hydrophobic tail (NHT, located on HEV ORF2 aa368-460). MATERIALS & METHODS: Flu
HA1, HIV gp41/gp120/p24, HBsAg and HPV16 L2 were fused with NHT, expressed in
Escherichia coli and subjected to self-assembly in vitro. Nanosized particles
were characterized by size-exclusion chromatography and negative electron
microscopy. Immunogenicity was assessed in mice. RESULTS: All the NHT-fused
proteins spontaneously formed nanoparticulates and presented with immunogenicity
approximately 2-log over their nonassembling forms. CONCLUSION: Protein self
assembly provides an attractive means to create nanosized particles that bear
specific antigens. Our strategy outlines a novel and shared method for the design
of immunogenic nanoparticles.
PMID- 27499053
TI - Streptococcus agalactiae from pregnant women: antibiotic and heavy-metal
resistance mechanisms and molecular typing.
AB - We investigated the antibiotic and heavy-metal resistance mechanisms, virulence
genes and clonal relationships of macrolide- and/or lincosamide-resistant (M+/
LR) Streptococcus agalactiae (group B Streptococcus, GBS) isolates from pregnant
women in La Rioja in Northern Spain, a region with a significant immigrant
population. In total 375 GBS isolates were recovered during 2011. About three
quarters of isolates were from European nationals and the remainder distributed
among 23 other nationalities. Seventy-five (20%) were classified as M+/-LR
strains and 28 (37%) of these were resistant to ?3 classes of antibiotics.
Capsular serotypes III (29.3%), V (21.3%) and II (12%) were the most frequent. A
wide variety of antibiotic resistance genes were detected in M+/-LR strains;
notably, 5.3% harboured the lsa(C) gene associated with cross-resistance, and
tet(W) was identified in a single strain. We report, for the first time, the
detection of cadmium and copper resistance encoded by tcrB + cadA + cadC genes in
20 M+/-LR strains, which raises the possibility of co-selection of antibiotic and
heavy-metal resistance disseminated through mobile genetic elements. The M+/-LR
strains were highly diverse by DNA macrorestriction profiles (65 patterns) and 16
multilocus sequence types (STs) distributed among six clonal complexes; the most
frequent were ST1, ST19, and ST12, and two strains were novel (ST586 and ST601).
In conclusion, a wide diversity of genetic lineages of macrolide, lincosamide and
heavy-metal- resistant GBS strains was observed in an ethnically diverse maternal
population.
PMID- 27499054
TI - Peer counselling for the promotion of long-acting, reversible contraception among
teens: a randomised, controlled trial.
AB - AIM: To evaluate the impact peer counselling has on same-day desire for long
acting, reversible contraception (LARC) among adolescents attending a family
planning clinic. METHODS: A randomised, controlled trial of 110 adolescent
females attending an outpatient clinic for contraception in 2013. Adolescents
received either brief peer counselling about LARC with routine contraceptive
counselling, or routine counselling alone. Bivariate analyses and multivariable
logistic regression assessed the primary outcome of same-day desire for LARC and
secondary outcomes of change in knowledge and attitudes regarding LARC. RESULTS:
Peer counselling was well received and 70% reported that it was helpful in
contraceptive decision-making. Peer counselling did not affect same-day desire
for LARC, however, adolescents who received the intervention were more likely to
report increased knowledge and positive change in attitudes towards LARC
(adjusted odds ratios: 6.6 (95% confidence interval: 2.0-22.0 and 6.4 (1.6-26.8),
respectively). Factors positively associated with same-day LARC desire included
greater reported peer contraceptive influence, peer use of LARC and social
support. Twenty of the 36 adolescents who desired LARC at the end of their clinic
visit did not receive one most commonly due to a need to schedule a specific
appointment for the procedure and the need to return during a menstrual period
for intrauterine device placement. CONCLUSION: While brief, point-of-care peer
counselling is well received, and can increase adolescent knowledge and positive
attitude about our most effective contraceptive methods, barriers to same-day
LARC placement limit immediate use.
PMID- 27499055
TI - The nonequilibrium glassy dynamics of self-propelled particles.
AB - We study the glassy dynamics taking place in dense assemblies of athermal active
particles that are driven solely by a nonequilibrium self-propulsion mechanism.
Active forces are modeled as an Ornstein-Uhlenbeck stochastic process,
characterized by a persistence time and an effective temperature, and particles
interact via a Lennard-Jones potential that yields well-studied glassy behavior
in the Brownian limit, which is obtained as the persistence time vanishes. By
increasing the persistence time, the system departs more strongly from thermal
equilibrium and we provide a comprehensive numerical analysis of the structure
and dynamics of the resulting active fluid. Finite persistence times profoundly
affect the static structure of the fluid and give rise to nonequilibrium velocity
correlations that are absent in thermal systems. Despite these nonequilibrium
features, for any value of the persistence time we observe a nonequilibrium glass
transition as the effective temperature is decreased. Surprisingly, increasing
departure from thermal equilibrium is found to promote (rather than suppress) the
glassy dynamics. Overall, our results suggest that with increasing persistence
time, microscopic properties of the active fluid change quantitatively, but the
general features of the nonequilibrium glassy dynamics observed with decreasing
the effective temperature remain qualitatively similar to those of thermal glass
formers.
PMID- 27499056
TI - Treatment with the selective serotonin reuptake inhibitor, fluoxetine, attenuates
the fish hypoxia response.
AB - The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX), the active
ingredient of the antidepressant drug Prozac, inhibits reuptake of the
neurotransmitter, serotonin (5-HT; 5-hydroxytryptamine), into cells by the 5-HT
transporter (SERT). Given the role of 5-HT in oxygen detection and the
cardiovascular and ventilatory responses of fish to hypoxia, we hypothesized that
treatment of the Gulf toadfish, Opsanus beta, with FLX would interfere with their
response to hypoxia. Toadfish treated intra-arterially with 3.4 MUg.g(-1) FLX
under normoxic conditions displayed a transient tachycardia and a biphasic caudal
arterial blood pressure (PCA) response that are in direct conflict with the
typical hypoxia response. Fish injected intraperitoneally with FLX under normoxia
had resting cardiovascular and ventilatory parameters similar to controls. Upon
exposure to hypoxia, control toadfish exhibit a significant bradycardia,
reduction in PCA and an increase in ventilatory amplitude (VAMP) without any
changes in ventilatory frequency (fV). Fish treated IP with 10 MUg.g(-1) FLX
showed an interference in the cardiovascular and ventilatory response to hypoxia.
Interestingly, when treated with 25 MUg.g(-1) FLX, the bradycardia and VAMP
response to hypoxia were similar to control fish while the PCA response to
hypoxia was further inhibited. These results suggest that SERT inhibition by FLX
may hinder survival in hypoxia.
PMID- 27499057
TI - Blue-light activated rapid polymerization for defect-free bulk Cu(i)-catalyzed
azide-alkyne cycloaddition (CuAAC) crosslinked networks.
AB - A visible-light (470 nm wavelength) sensitive Type II photoinitiator system is
developed for bulk Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions
in crosslinked networks. The accelerated photopolymerization eliminates UV
mediated azide decomposition allowing for the formation of defect-free glassy
networks which exhibit a narrow glass transition temperature.
PMID- 27499058
TI - Enhanced electrocatalytic activity of nitrogen-doped olympicene/graphene hybrids
for the oxygen reduction reaction.
AB - Developing inexpensive and non-precious metal electrocatalysts for the oxygen
reduction reaction (ORR) is among the major goals in fuel cells. Herein, by using
density-functional theory calculations, we show that N-doped olympicene/graphene
hybrids exhibit unexpectedly high ORR catalytic activity-even comparable to that
of the Pt(111) surface. Both graphitic-type and pyridine-type N-doped
olympicene/graphene hybrids are highly active for the ORR and have good CO
tolerance. The formation of the second H2O molecule is the rate-determining step
for the ORR with the graphitic-type hybrid, whereas on the pyridine-type hybrid,
it is the formation of OOH. Note that N-doped olympicene/graphene hybrid
materials combine the high reactivity of olympicene and the high electrical
conductivity of graphene, which allows them to be potentially used as low-cost
and non-precious-metal ORR catalysts.
PMID- 27499059
TI - Clinical features and outcome of epinephrine-induced takotsubo syndrome: Analysis
of 33 published cases.
AB - BACKGROUND: Takotsubo syndrome (TS) may be triggered by innumerable physical
stress factors including epinephrine administration. The aim of this study is to
report on the clinical features and outcome of epinephrine-induced TS (Epi-TS) in
a large cohort of published cases. METHODS: A computer assisted search of the
electronic data base Pubmed was performed from 1990 to 2014. All cases deemed to
have Epi-TS were retrieved and compared to the large recent report by Templin et
al. (All-TS). RESULTS: Thirty-three cases of Epi-TS were retrieved from the
literature and compared to 1750 cases of All-TS. Chest pain as a presenting
symptom occurred in 45% of cases. The Epi-TS patients were on average 20.6years
younger than All-TS patients (p<0.0001). The women were still predominating in
Epi-TS but in a significantly lower percentage compared to ALL-TS (73% in Epi-TS
vs 89.8% in All-TS, p=0.0054). One third of the Epi-TS cases had basal pattern of
TS compared to 2.2% of cases reported in All-TS. Epi-TS cases were characterized
by high complication rates, which occurred in 57.6%. The most important risk
factor for the development of TS complication was the accidental administration
(P<0.001) and the dose of >1mg epinephrine (p=0.02). In spite of high
complication rates, the recovery was rapid with no in-hospital mortality.
CONCLUSION: Epi-TS is characterized by a dramatic rapid onset of symptoms after
epinephrine administration. Almost half of the cases had apical sparing and one
third basal pattern of TS. In spite of high complication rates, the prognosis was
good with no in-hospital mortality.
PMID- 27499060
TI - Review: Stent fracture in the drug-eluting stent era.
AB - Stent fracture has been recognized as one cause of stent failure and has been
associated with in-stent restenosis and stent thrombosis, even in 2nd-generation
drug-eluting stents. Given the wide use of drug-eluting stents and paucity of
contemporary data available concerning stent fracture, we reviewed clinical
studies and the Food and Drug Administration's Manufacturer and User Device
Experience (MAUDE) database to analyze the current trends, mechanisms,
predictors, outcomes and treatment for stent fracture.
PMID- 27499061
TI - Aerobic versus Anaerobic Microbial Degradation of Clothianidin under Simulated
California Rice Field Conditions.
AB - Microbial degradation of clothianidin was characterized under aerobic and
anaerobic California rice field conditions. Rate constants (k) and half-lives
(DT50) were determined for aerobic and anaerobic microcosms, and an enrichment
experiment was performed at various nutrient conditions and pesticide
concentrations. Temperature effects on anaerobic degradation rates were
determined at 22 +/- 2 and 35 +/- 2 degrees C. Microbial growth was assessed in
the presence of various pesticide concentrations, and distinct colonies were
isolated and identified. Slow aerobic degradation was observed, but anaerobic
degradation occurred rapidly at both 25 and 35 degrees C. Transformation rates
and DT50 values in flooded soil at 35 +/- 2 degrees C (k = -7.16 * 10(-2) +/-
3.08 * 10(-3) day(-1), DT50 = 9.7 days) were significantly faster than in 25 +/-
2 degrees C microcosms (k= -2.45 * 10(-2) +/- 1.59 * 10(-3) day(-1), DT50 = 28.3
days). At the field scale, biodegradation of clothianidin will vary with extent
of oxygenation.
PMID- 27499062
TI - Bilateral hamartomatous medullary lipoma within the nasal turbinate bones in a
cynomolgus monkey (Macaca fascicularis).
AB - A 15-year-old male cynomolgus monkey (Macaca fascicularis) showed large bilateral
masses in the maxillary sinus. In histopathological examination, both masses
revealed benign medullary lipomas within the turbinate bones. The tumors were
composed of well-developed lipocytes, trabecular bones and a few blood vessels.
Although we initially diagnosed the tumor as bilateral lipomas in the nasal
turbinates, it was not differentiated from lipomatous hamartoma. Findings, such
as unique symmetrical proliferation, lack of border from the normal marrow and
the intact surrounding tissue, indicated a lipomatous hamartoma/hamartomatous
lipoma, thought to be a suitable diagnosis of the lesion. Of most interest was
that such a proliferating lesion occurred in the nasal turbinate.
PMID- 27499063
TI - Free-energy studies reveal a possible mechanism for oxidation-dependent
inhibition of MGL.
AB - The function of monoacylglycerol lipase (MGL), a key actor in the hydrolytic
deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2AG), is tightly
controlled by the cell's redox state: oxidative signals such as hydrogen peroxide
suppress MGL activity in a reversible manner through sulfenylation of the
peroxidatic cysteines, C201 and C208. Here, using as a starting point the crystal
structures of human MGL (hMGL), we present evidence from molecular dynamics and
metadynamics simulations along with high-resolution mass spectrometry studies
indicating that sulfenylation of C201 and C208 alters the conformational
equilibrium of the membrane-associated lid domain of MGL to favour closed
conformations of the enzyme that do not permit the entry of substrate into the
active site.
PMID- 27499065
TI - Erratum: Biomarkers in the Management of Difficult Asthma.
AB - In the review entitled, 'Biomarkers in the Management of Difficult Asthma'
published in Current Topics in Medicinal Chemistry, 2016, 16, 1561-1573, the
authors name should be in the following format. Florence Schleich*, Sophie
Demarche and Renaud Louis. Respiratory Medicine, GIGA I", CHU Sart-Tilman B35,
4000 Liege, Belgium.
PMID- 27499064
TI - Long-term effectiveness of initiating non-nucleoside reverse transcriptase
inhibitor- versus ritonavir-boosted protease inhibitor-based antiretroviral
therapy: implications for first-line therapy choice in resource-limited settings.
AB - INTRODUCTION: In many resource-limited settings, combination antiretroviral
therapy (cART) failure is diagnosed clinically or immunologically. As such, there
is a high likelihood that patients may stay on a virologically failing regimen
for a substantial period of time. Here, we compared the long-term impact of
initiating non-nucleoside reverse transcriptase inhibitor (NNRTI)- versus boosted
protease inhibitor (bPI)-based cART in British Columbia (BC), Canada. METHODS: We
followed prospectively 3925 ART-naive patients who started NNRTIs (N=1963, 50%)
or bPIs (N=1962; 50%) from 1 January 2000 until 30 June 2013 in BC. At six
months, we assessed whether patients virologically failed therapy (a plasma viral
load (pVL) >50 copies/mL), and we stratified them based on the pVL at the time of
failure <=500 versus >500 copies/mL. We then followed these patients for another
six months and calculated their probability of achieving subsequent viral
suppression (pVL <50 copies/mL twice consecutively) and of developing drug
resistance. These probabilities were adjusted for fixed and time-varying factors,
including cART adherence. RESULTS: At six months, virologic failure rates were
9.5 and 14.3 cases per 100 person-months for NNRTI and bPI initiators,
respectively. NNRTI initiators who failed with a pVL <=500 copies/mL had a 16%
higher probability of achieving subsequent suppression at 12 months than bPI
initiators (0.81 (25th-75th percentile 0.75-0.83) vs. 0.72 (0.61-0.75)). However,
if failing NNRTI initiators had a pVL >500 copies/mL, they had a 20% lower
probability of suppressing at 12 months than pVL-matched bPI initiators (0.37
(0.29-0.45) vs. 0.46 (0.38-0.54)). In terms of evolving HIV drug resistance,
those who failed on NNRTI performed worse than bPI in all scenarios, especially
if they failed with a viral load >500 copies/mL. CONCLUSIONS: Our results show
that patients who virologically failed at six months on NNRTI and continued on
the same regimen had a lower probability of subsequently achieving viral
suppression and a higher chance of evolving HIV drug resistance. These results
suggest that improving access to regular virologic monitoring is critically
important, especially if NNRTI-based cART is to remain a preferred choice for
first-line therapy in resource-limited settings.
PMID- 27499067
TI - Winner of the Annals of Science Prize for 2015.
PMID- 27499066
TI - Erratum to: Abyssicoccus albus gen. nov., sp. nov., a novel member of the family
Staphylococcaceae isolated from marine sediment of the Indian Ocean.
PMID- 27499068
TI - Increased EZH2 and decreased osteoblastogenesis during local irradiation-induced
bone loss in rats.
AB - Radiation therapy is commonly used to treat cancer patients but exhibits adverse
effects, including insufficiency fractures and bone loss. Epigenetic regulation
plays an important role in osteogenic differentiation of bone marrow mesenchymal
stem cells (BMSCs). Here, we reported local bone changes after single-dose
exposure to (137)CS irradiation in rats. Femur bone mineral density (BMD) and
trabecular bone volume in the tibia were significantly decreased at 12 weeks
after irradiation. Micro-CT results showed that tBMD, Tb.h and Tb.N were also
significantly reduced at 12 weeks after irradiation exposure. ALP-positive
OB.S/BS was decreased by 42.3% at 2 weeks after irradiation and was decreased by
50.8% at 12 weeks after exposure. In contrast to the decreased expression of
Runx2 and BMP2, we found EZH2 expression was significantly increased at 2 weeks
after single-dose (137)CS irradiation in BMSCs. Together, our results
demonstrated that single-dose (137)CS irradiation induces BMD loss and the
deterioration of bone microarchitecture in the rat skeleton. Furthermore, EZH2
expression increased and osteoblastogenesis decreased after irradiation. The
underlying mechanisms warrant further investigation.
PMID- 27499069
TI - Risk is for the rich? Childhood vaccination resistance and a Culture of Health.
AB - Childhood vaccination resistance has given rise to outbreaks of diseases, which
had been virtually eliminated in the developed world. A parent's decision to
forego vaccination for their child is a private choice that can have collective
outcomes. This article takes a two-pronged approach to unraveling the puzzle of
perceiving vaccines as dangerous in view of evidence that testifies to their
effectiveness and relative safety. First, it draws on fifty-seven years of
newspaper articles on vaccines to outline the public narratives. Second, it uses
school-level data from New York and California to explore how these public
narratives shape a geography of vaccination rates. We have two main findings.
First, we find that while risk has always been a feature of vaccine narratives,
the perception that the risks of vaccines out-weigh the benefits has grown. By
the millennium, some began to view medical treatments as sources of risk rather
than cure. Second, our geography of childhood vaccination reveals two distinct
vaccine worlds. Affluence governs one world. Poverty governs the other. The
geographic locales where vaccination rates are low enable us to contrast the
difference between imagining risk, the prerogative of the affluent, and being at
risk, the fate of the poor. Vaccination resistance speaks directly to a Culture
of Health as it poses questions about the collective perception of risk and its
relation to social inequality and solidarity.
PMID- 27499070
TI - Room temperature differential conductance measurements of triethylamine molecules
adsorbed on Si(001).
AB - We have measured the differential conductance of the triethylamine molecule
(N(CH2CH3)3) adsorbed on Si(001)-2 * 1 at room temperature using scanning
tunneling spectroscopy. Triethylamine can be engaged in a dative bonding with a
silicon dimer, forming a Si-Si-N(CH2CH3)3 unit. We have examined the datively
bonded adduct, either as an isolated molecule, or within an ordered molecular
domain (reconstructed 4 * 2). The differential conductance curves, supported by
DFT calculations, show that in the explored energy window (+/-2.5 near the Fermi
level) the main features stem from the uncapped dangling bonds of the reacted
dimer and of the adjacent unreacted ones that are electronically coupled The
formation of a molecular domain, in which one dimer in two is left unreacted, is
reflected in a shift of the up dimer atom occupied level away from the Fermi
level, likely due to an increased pi-bonding strength. In stark contrast with the
preceding, pairs of dissociated molecule (a minority species) are electronically
decoupled from the dimer dangling bond states. DFT calculation show that the lone
pair of the Si-N(CH2CH3)2 is a shallow level, that is clearly seen in the
differential conductance curve.
PMID- 27499071
TI - High expression of miR-15b predicts poor prognosis for hepatocellular carcinoma
after curative hepatectomy.
AB - The present study aimed to analyze the role and mechanism of miR-15b in
hepatocellular carcinoma (HCC) after curative hepatectomy. Tissue samples from 13
patients with HCC who were operated on at the Chinese PLA General Hospital from
March 2014 to May 2014 were collected. A consecutive 156 untreated patients with
HCC who received curative hepatectomy at the Chinese PLA General Hospital
(Beijing, China) from May 2008 to March 2009 were enrolled, and their
corresponding para-tumoral and normal tissue samples were acquired. Subsequently,
anti-miR-15b (inhibitor) was transfected into human HCC HepG2 cells. It was
observed that high expression of miR-15b promoted cell proliferation of the HCC
cells, while low expression of miR-15b suppressed cell growth and induced the
apoptosis of HepG2 cells. It was found that overall survival of the patients with
low miR-15b was increased, compared with the overall survival of the patients
with high miR-15b expression. In addition, low expression of miR-15b suppressed
the growth of HepG2 cells by suppression of transforming growth factor-beta (TGF
beta), TbetaRI and Smad2 protein expression. Meanwhile, low expression of miR-15b
significantly activated Bax protein expression and caspase-3 activity in the
HepG2 cells. The study results revealed that high expression of miR-15b could
predict the poor prognosis of hepatocellular carcinoma after curative hepatectomy
through TGF-beta/TbetaRI-Smad2-cyclin D1/Bax.
PMID- 27499072
TI - Mental illness and the right to vote.
PMID- 27499074
TI - The effects of 405 nm light on bacterial membrane integrity determined by salt
and bile tolerance assays, leakage of UV-absorbing material and SYTOX green
labelling.
AB - Bacterial inactivation by 405 nm light is accredited to the photoexcitation of
intracellular porphyrin molecules resulting in energy transfer and the generation
of reactive oxygen species that impart cellular oxidative damage. The specific
mechanism of cellular damage, however, is not fully understood. Previous work has
suggested that destruction of nucleic acids may be responsible for inactivation;
however, microscopic imaging has suggested membrane damage as a major constituent
of cellular inactivation. This study investigates the membrane integrity of
Escherichia coli and Staphylococcus aureus exposed to 405 nm light. Results
indicated membrane damage to both species, with loss of salt and bile tolerance
by S. aureus and E. coli, respectively, consistent with reduced membrane
integrity. Increased nucleic acid release was also demonstrated in 405 nm light
exposed cells, with up to 50 % increase in DNA concentration into the
extracellular media in the case of both organisms. SYTOX green fluorometric
analysis, however, demonstrated contradictory results between the two test
species. With E. coli, increasing permeation of SYTOX green was observed
following increased exposure, with >500 % increase in fluorescence, whereas no
increase was observed with S. aureus. Overall, this study has provided good
evidence that 405 nm light exposure causes loss of bacterial membrane integrity
in E. coli, but the results with S. aureus are more difficult to explain. Further
work is required to gain greater understanding of the inactivation mechanism in
different bacterial species, as there are likely to be other targets within the
cell that are also impaired by the oxidative damage from photo-generated reactive
oxygen species.
PMID- 27499076
TI - Synthesis and Modification of Zn-doped TiO2 Nanoparticles for the Photocatalytic
Degradation of Tetracycline.
AB - The synthesis of Zn-doped TiO2 nanoparticles by solgel method was investigated in
this study, as well as its modification by H2 O2 . The catalyst was characterized
by transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller,
UV-visible reflectance spectra and X-ray photoelectron spectroscopy (XPS). The
results indicated that doping Zn into TiO2 nanoparticles could inhibit the
transformation from anatase phase to rutile phase. Zn existed as the second
valence oxidation state in the Zn-doped TiO2 . Zn-doped TiO2 that was synthesized
by 5% Zn doping at 450 degrees C exhibited the best photocatalytic activity.
Then, the H2 O2 modification further enhanced the photocatalytic activity. Zn
doping and H2 O2 modifying narrowed the band gap and efficiently increased the
optical absorption in visible region. The optimal degradation rate of
tetracycline by Zn-doped TiO2 and H2 O2 modified Zn-doped TiO2 was 85.27% and
88.14%. Peroxide groups were detected in XPS analysis of H2 O2 modified Zn-doped
TiO2 , favoring the adsorption of visible light. Furthermore, Zn-doped TiO2
modified by H2 O2 had relatively good reusability, exhibiting a potential
practical application for tetracycline's photocatalytic degradation.
PMID- 27499075
TI - Investigation of the functional role of human Interleukin-8 gene haplotypes by
CRISPR/Cas9 mediated genome editing.
AB - Interleukin-8 (IL-8) gene polymorphisms have been considered as susceptibility
factors in periodontal disease. However, the functional roles of IL-8 gene
haplotypes have not been investigated. Here, we demonstrate for the first time
the use of the CRISPR/Cas9 system to engineer the IL-8 gene, and tested the
functionality of different haplotypes. Two sgRNAs vectors targeting the IL-8 gene
and the naked homologous repair DNA carrying different haplotypes were used to
successfully generate HEK293T cells carrying the AT genotype at the first SNP -
rs4073 (alias -251), TT genotype at the second SNP - rs2227307 (alias +396), TC
or CC genotypes at the third SNP - rs2227306 (alias +781) at the IL-8 locus. When
stimulated with Poly I:C, ATC/TTC haplotype, cells significantly up-regulated the
IL-8 at both transcriptional and translational levels. To test whether ATC/TTC
haplotype is functional, we used a trans-well assay to measure the transmigration
of primary neutrophils incubated with supernatants from the Poly I:C stimulation
experiment. ATC/TTC haplotype cells significantly increased transmigration of
neutrophils confirming the functional role for this IL-8 haplotype. Taken
together, our data provides evidence that carriage of the ATC/TTC haplotype in
itself may increase the influx of neutrophils in inflammatory lesions and
influence disease susceptibility.
PMID- 27499077
TI - Herbivorax saccincola gen. nov., sp. nov., a cellulolytic, anaerobic,
thermophilic bacterium isolated via in sacco enrichments from a lab-scale biogas
reactor.
AB - A novel Gram-stain-positive, rod-shaped, anaerobic, thermophilic bacterium,
strain GGR1T, was isolated from a thermophilic lab-scale biogas fermenter. The
novel organism was effectively degrading crystalline cellulose. It seems to play
a role in remineralization of plant biomass by hydrolysing its polysaccharides.
16S rRNA gene comparative sequence analysis demonstrated that the isolate formed
a hitherto unknown subline within the family Ruminococcaceae. The closest
phylogenetic relative of GGR1T among the taxa with validly published names was
Clostridiumthermocellum, sharing 94.3 % 16S rRNA gene sequence similarity. Strain
GGR1T was catalase-negative, indole-negative and produced acetate and ethanol as
major end-products during fermentative cellulose utilization. The major cellular
fatty acids (>1 %) were 16 : 0 iso fatty acid and 16 : 0 fatty acid. Cells were
rod shaped and grew optimally at 60 degrees C and pH 7.0. The DNA G+C content
was 34.9 mol%. A novel genus and species, Herbivoraxsaccincola gen. nov., sp.
nov., is proposed on the basis of phylogenetic analysis and physiological
properties of the novel isolate. Strain GGR1T (=DSM 101079T=CECT 9155T)
represents the type strain for the novel genus and novel species
Herbivoraxsaccincola gen. nov., sp. nov.
PMID- 27499078
TI - Identification of Mycobacterium tuberculosis in the cerebrospinal fluid of
patients with meningitis using nested PCR.
AB - Tuberculous meningitis (TBM) is the most severe form of tuberculosis. It is
caused by Mycobacterium tuberculosis (M. tuberculosis; MT) and it is very
difficult to diagnose. The symptoms are similar to other infectious neurological
diseases, such as neurocysticercosis, neuroborreliosis, or herpes viral
infection. The aim of this study was to identify tuberculosis (TB) in cases of
meningitis with clinical and laboratory evidence suggestive of TBM, and to
confirm our findings with molecular tests for TB infection. We recruited patients
with neurological symptoms who were examined at the neurology services of
Hospitals of Instituto Mexicano del Seguro Social (IMSS) in Mexico City. A total
of 144 consecutive patients with suggestive infectious meningitis were initially
included; 94 cases of meningitis with clinical and laboratory evidence suggestive
of TBM were included, but only 50 of these cases fulfilled the criteria for
probable TBM. As the controls, we included 50 cases of meningitis with clinical
and laboratory evidence suggestive of non-TBM. Cerebrospinal fluid (CSF) was
collected from all 100 patients (cases and controls) and tested for TB by
multiplex and nested PCR analyses. Nested PCR detected 0.1 fg of M. tuberculosis
DNA. TB infection was confirmed with molecular tests in 49 patients from the 50
cases suggestive of TBM and in 1 of the 50 non-TBM cases. The analysis exhibited
a sensitivity of 98.0%, a specificity of 92.0%, a positive predictive value of
88.0% and a negative predictive value of 98.0%. The use CSF for the analyses
proved to be effective for the rapid diagnosis of TBM using a developed system of
multiplex and nested PCR analyses in patients presenting neurological symptoms.
PMID- 27499079
TI - Computational screening of iodine uptake in zeolitic imidazolate frameworks in a
water-containing system.
AB - Iodine capture is of great environmental significance due to the high toxicity
and volatility of I2. Here we conduct a systematic computational investigation of
iodine adsorption in zeolitic imidazolate frameworks (ZIFs) by adopting the grand
canonical Monte Carlo (GCMC) simulation and the density functional theory (DFT)
method. The results confirm the vital structural factors for iodine adsorption at
298 K and moderate pressures including metal sites, organic linkers, symmetry,
and topology types. The uptake will be enhanced by active metal sites, the simple
imidazolate linker and single asymmetric linkers with polar functional groups.
The symmetry effect is stronger than the surface properties. Meanwhile low steric
hindrance is more beneficial than polar functional groups to iodine adsorption.
The specific topology types like mer bringing large surface areas and large
diameter cages result in high iodine capacities. Iodine molecules tend to locate
in cages with large diameters and aggregates along the sides of cages. In
contrast, water prefers small diameter cages. In hydrophilic materials, water has
a negative impact on iodine uptake due to its similar adsorption sites to iodine.
The selectivity of iodine over water increases with increasing water content due
to the large diameter cages of ZIFs. This work proves that ZIFs can be identified
as efficient and economical adsorbents with high diversity for iodine in a water
containing system. Furthermore, it provides comprehensive insights into key
structural factors for iodine uptake and separation in silver-free porous solids.
PMID- 27499080
TI - Virus persistence and recrudescence after Ebola virus disease: what are the risks
to healthcare workers?
PMID- 27499081
TI - Loss and Gain of MeCP2 Cause Similar Hippocampal Circuit Dysfunction that Is
Rescued by Deep Brain Stimulation in a Rett Syndrome Mouse Model.
AB - Loss- and gain-of-function mutations in methyl-CpG-binding protein 2 (MECP2)
underlie two distinct neurological syndromes with strikingly similar features,
but the synaptic and circuit-level changes mediating these shared features are
undefined. Here we report three novel signs of neural circuit dysfunction in
three mouse models of MECP2 disorders (constitutive Mecp2 null, mosaic Mecp2(+/
), and MECP2 duplication): abnormally elevated synchrony in the firing activity
of hippocampal CA1 pyramidal neurons, an impaired homeostatic response to
perturbations of excitatory-inhibitory balance, and decreased excitatory synaptic
response in inhibitory neurons. Conditional mutagenesis studies revealed that
MeCP2 dysfunction in excitatory neurons mediated elevated synchrony at baseline,
while MeCP2 dysfunction in inhibitory neurons increased susceptibility to
hypersynchronization in response to perturbations. Chronic forniceal deep brain
stimulation (DBS), recently shown to rescue hippocampus-dependent learning and
memory in Mecp2(+/-) (Rett) mice, also rescued all three features of hippocampal
circuit dysfunction in these mice.
PMID- 27499082
TI - Interaction between Spatial and Feature Attention in Posterior Parietal Cortex.
AB - Lateral intraparietal (LIP) neurons encode a vast array of sensory and cognitive
variables. Recently, we proposed that the flexibility of feature representations
in LIP reflect the bottom-up integration of sensory signals, modulated by feature
based attention (FBA), from upstream feature-selective cortical neurons.
Moreover, LIP activity is also strongly modulated by the position of space-based
attention (SBA). However, the mechanisms by which SBA and FBA interact to
facilitate the representation of task-relevant spatial and non-spatial features
in LIP remain unclear. We recorded from LIP neurons during performance of a task
that required monkeys to detect specific conjunctions of color, motion direction,
and stimulus position. Here we show that FBA and SBA potentiate each other's
effect in a manner consistent with attention gating the flow of visual
information along the cortical visual pathway. Our results suggest that linear
bottom-up integrative mechanisms allow LIP neurons to emphasize task-relevant
spatial and non-spatial features.
PMID- 27499083
TI - Somatodendritic Expression of JAM2 Inhibits Oligodendrocyte Myelination.
AB - Myelination occurs selectively around neuronal axons to increase the efficiency
and velocity of action potentials. While oligodendrocytes are capable of
myelinating permissive structures in the absence of molecular cues, structurally
permissive neuronal somata and dendrites remain unmyelinated. Utilizing a
purified spinal cord neuron-oligodendrocyte myelinating co-culture system, we
demonstrate that disruption of dynamic neuron-oligodendrocyte signaling by
chemical cross-linking results in aberrant myelination of the somatodendritic
compartment of neurons. We hypothesize that an inhibitory somatodendritic cue is
necessary to prevent non-axonal myelination. Using next-generation sequencing and
candidate profiling, we identify neuronal junction adhesion molecule 2 (JAM2) as
an inhibitory myelin-guidance molecule. Taken together, our results demonstrate
that the somatodendritic compartment directly inhibits myelination and suggest a
model in which broadly indiscriminate myelination is tailored by inhibitory
signaling to meet local myelination requirements.
PMID- 27499084
TI - Regrowth of Serotonin Axons in the Adult Mouse Brain Following Injury.
AB - It is widely believed that damaged axons in the adult mammalian brain have little
capacity to regrow, thereby impeding functional recovery after injury. Studies
using fixed tissue have suggested that serotonin neurons might be a notable
exception, but remain inconclusive. We have employed in vivo two-photon
microscopy to produce time-lapse images of serotonin axons in the neocortex of
the adult mouse. Serotonin axons undergo massive retrograde degeneration
following amphetamine treatment and subsequent slow recovery of axonal density,
which is dominated by new growth with little contribution from local sprouting. A
stab injury that transects serotonin axons running in the neocortex is followed
by local regression of cut serotonin axons and followed by regrowth from cut ends
into and across the stab rift zone. Regrowing serotonin axons do not follow the
pathways left by degenerated axons. The regrown axons release serotonin and their
regrowth is correlated with recovery in behavioral tests.
PMID- 27499085
TI - Neurons in Macaque Area V4 Are Tuned for Complex Spatio-Temporal Patterns.
AB - To deepen our understanding of object recognition, it is critical to understand
the nature of transformations that occur in intermediate stages of processing in
the ventral visual pathway, such as area V4. Neurons in V4 are selective to local
features of global shape, such as extended contours. Previously, we found that V4
neurons selective for curved elements exhibit a high degree of spatial variation
in their preference. If spatial variation in curvature selectivity was also
marked by distinct temporal response patterns at different spatial locations,
then it might be possible to untangle this information in subsequent processing
based on temporal responses. Indeed, we find that V4 neurons whose receptive
fields exhibit intricate selectivity also show variation in their temporal
responses across locations. A computational model that decodes stimulus identity
based on population responses benefits from using this temporal information,
suggesting that it could provide a multiplexed code for spatio-temporal features.
PMID- 27499086
TI - Efficient Receptive Field Tiling in Primate V1.
AB - The primary visual cortex (V1) encodes a diverse set of visual features,
including orientation, ocular dominance (OD), and spatial frequency (SF), whose
joint organization must be precisely structured to optimize coverage within the
retinotopic map. Prior experiments have only identified efficient coverage based
on orthogonal maps. Here we used two-photon calcium imaging to reveal an
alternative arrangement for OD and SF maps in macaque V1; their gradients run
parallel but with unique spatial periods, whereby low-SF regions coincide with
monocular regions. Next we mapped receptive fields and found surprisingly precise
micro-retinotopy that yields a smaller point-image and requires more efficient
inter-map geometry, thus underscoring the significance of map relationships.
While smooth retinotopy is constraining, studies suggest that it improves both
wiring economy and the V1 population code read downstream. Altogether, these data
indicate that connectivity within V1 is finely tuned and precise at the level of
individual neurons.
PMID- 27499087
TI - Erythrocytes Are Oxygen-Sensing Regulators of the Cerebral Microcirculation.
AB - Energy production in the brain depends almost exclusively on oxidative
metabolism. Neurons have small energy reserves and require a continuous supply of
oxygen (O2). It is therefore not surprising that one of the hallmarks of normal
brain function is the tight coupling between cerebral blood flow and neuronal
activity. Since capillaries are embedded in the O2-consuming neuropil, we have
here examined whether activity-dependent dips in O2 tension drive capillary
hyperemia. In vivo analyses showed that transient dips in tissue O2 tension
elicit capillary hyperemia. Ex vivo experiments revealed that red blood cells
(RBCs) themselves act as O2 sensors that autonomously regulate their own
deformability and thereby flow velocity through capillaries in response to
physiological decreases in O2 tension. This observation has broad implications
for understanding how local changes in blood flow are coupled to synaptic
transmission.
PMID- 27499088
TI - Identification of novel miRNAs from drought tolerant rice variety Nagina 22.
AB - MicroRNAs regulate a spectrum of developmental and biochemical processes in
plants and animals. Thus, knowledge of the entire miRNome is essential to
understand the complete regulatory schema of any organism. The current study
attempts to unravel yet undiscovered miRNA genes in rice. Analysis of small RNA
libraries from various tissues of drought-tolerant 'aus' rice variety Nagina 22
(N22) identified 71 novel miRNAs. These were validated based on precursor hairpin
structure, small RNA mapping pattern, 'star' sequence, conservation and
identification of targets based on degradome data. While some novel miRNAs were
conserved in other monocots and dicots, most appear to be lineage-specific. They
were segregated into two different classes based on the closeness to the
classical miRNA definition. Interestingly, evidence of a miRNA-like cleavage was
found even for miRNAs that lie beyond the classical definition. Several novel
miRNAs displayed tissue-enriched and/or drought responsive expression. Generation
and analysis of the degradome data from N22 along with publicly available
degradome identified several high confidence targets implicated in regulation of
fundamental processes such as flowering and stress response. Thus, discovery of
these novel miRNAs considerably expands the dimension of the miRNA-mediated
regulation in rice.
PMID- 27499089
TI - 12/15-Lipoxygenase Inhibition Reverses Cognitive Impairment, Brain Amyloidosis,
and Tau Pathology by Stimulating Autophagy in Aged Triple Transgenic Mice.
AB - BACKGROUND: The 12/15-lipoxygenase (12/15-LO) enzyme is upregulated in the brains
of patients with Alzheimer's disease (AD), and its expression levels influence
the onset of the AD-like phenotype in mouse models. However, whether targeting
this pathway after the neuropathology and behavioral impairments have been
established remains to be investigated. METHODS: Triple transgenic (3xTg) mice
received either PD146176-a selective and specific pharmacological inhibitor of
12/15-LO-or placebo starting at 12 months of age for 12 weeks. They were then
assessed for the effect of the treatment on neuropathologies and behavioral
impairments. RESULTS: At the end of the study, mice in the control group showed a
worsening of memory and learning abilities, whereas mice receiving PD146176 were
undistinguishable from wild-type mice. The same group also had significantly
lower amyloid beta levels and deposition, less tau neuropathology, increased
synaptic integrity, and autophagy activation. Ex vivo and in vitro genetic and
pharmacological studies found that the mechanism involved in these effects was
the activation of neuronal autophagy. CONCLUSIONS: Our findings provide new
insights into the disease-modifying action of 12/15-LO pharmacological inhibition
and establish it as a viable therapeutic approach for patients with AD.
PMID- 27499090
TI - Schisandrin B inhibits cell proliferation and induces apoptosis in human
cholangiocarcinoma cells.
AB - Cholangiocarcinoma (CCA) is the second most common hepatic cancer with high
resistance to current chemotherapies and extremely poor prognosis. The present
study aimed to examine the effects of schisandrin B (Sch B) on CCA cells both in
vitro and in vivo and to examine its underlying mechanism. We found that Sch B
inhibited the viability and proliferation of CCA cells in a dose- and time
dependent manner as assessed by MTT and colony formation assays. The flow
cytometric assay revealed G0/G1 phase arrest in the Sch B-treated HCCC-9810 and
RBE cells. In addition, Sch B induced intrahepatic cholangiocarcinoma apoptosis
as shown by the results of Annexin V/PI double staining. Rhodamine 123 staining
revealed that Sch B decreased the mitochondrial membrane potential (DeltaPsim) in
a dose-dependent manner. Mechanistically, western blot analysis indicated that
Sch B induced apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9
and cleaved PARP, and by downregulating cyclin D1, Bcl-2 and CDK-4. Moreover, Sch
B significantly inhibited HCCC-9810 xenograft growth in athymic nude mice. In
summary, these findings suggest that Sch B exhibited potent antitumor activities
via the induction of CCA apoptosis and that Sch B may be a promising drug for the
treatment of CCA.
PMID- 27499091
TI - 18beta-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by
up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants.
AB - OBJECTIVES: 18beta-glycyrrhetinic acid (18beta-GA) has multiple beneficial and
therapeutic effects. However, its protective roles on methotrexate (MTX)-induced
renal injury are not well defined. In the present study, we investigated the
possible protective effects of 18beta-GA against MTX-induced nephrotoxicity in
rats. MATERIALS: 18beta-GA (50 and 100 mg/kg) was administered for 7 days either
before or after MTX. The rats were decapitated and kidney and serum samples were
collected. RESULTS: MTX-induced renal injury in rats was evidenced by the
significant (p < 0.001) increase in circulating kidney function markers and tumor
necrosis factor alpha (TNF-alpha), as well as the histopathological alterations.
MTX-induced rats exhibited significantly increased lipid peroxidation (p < 0.05)
and nitric oxide (p < 0.001) levels, with concomitant marked (p < 0.001) decline
in the antioxidant defenses. 18beta-GA, administered either before or after MTX,
produced a significant amelioration of circulating kidney function markers, TNF
alpha, kidney lipid peroxidation, nitric oxide, and antioxidant defenses. In
addition, 18beta-GA supplementation significantly up-regulated the mRNA abundance
of both nuclear factor-erythroid 2-related factor 2 (Nrf2) and hemoxygenase 1 (HO
1) in the kidney of MTX-induced rats. CONCLUSIONS: These results indicate that
18beta-GA has a protective effect on MTX-induced nephrotoxicity with possible
mechanisms of attenuating oxidative stress and inflammation through up-regulating
the Nrf2/ARE signaling. These findings make 18beta-GA candidate as a potent agent
in preventing MTX-induced kidney injury.
PMID- 27499092
TI - Design and characteristics evaluation of a novel teleoperated robotic
catheterization system with force feedback for vascular interventional surgery.
AB - In this paper, we proposed a novel master-slave robotic catheterization system
with force feedback for VIS (Vascular Interventional Surgery). The force feedback
to the operator on the master side is the key factor to improve the safety during
VIS. The developed system used the MR (magneto rheological) fluid to realize
force feedback, and it used the developed multidimensional monitoring interface
to realize the visualization of force feedback, the developed multidimensional
monitoring interface can monitor the motion information of the catheter and
contact force between catheter tip or side wall and blood vessel wall, and the
motion data of the catheter was collected and generated diagram for reference to
surgeon. We have developed a force sensor array to detect the contact force
between catheter tip or side wall and blood vessel wall. The force information
was detected by the developed contact force sensor array when the catheter
contacted with the blood vessel. The force feedback and multidimensional
information monitoring interface evaluation experiments were done, the tracking
characteristic evaluation experiments were also carried out, the experimental
results indicated that the developed novel robotic catheterization system with
force feedback and visualization of force feedback is effective for VIS, it can
improve the safety during VIS.
PMID- 27499093
TI - miR-625 suppresses tumour migration and invasion by targeting IGF2BP1 in
hepatocellular carcinoma.
PMID- 27499094
TI - Chromosomal, epigenetic and microRNA-mediated inactivation of LRP1B, a modulator
of the extracellular environment of thyroid cancer cells.
PMID- 27499095
TI - Elevated hydrostatic pressure enhances the motility and enlarges the size of the
lung cancer cells through aquaporin upregulation mediated by caveolin-1 and
ERK1/2 signaling.
AB - The mechanical characteristics presented in cancer microenvironment are known to
have pivotal roles in cancer metastasis, which accounts for the leading cause of
death from malignant tumors. However, while a uniformly distributed high
interstitial fluid pressure (IFP) is a common feature in solid tumors, the
effects of high IFP on the motility and invasiveness of cancer cells remain
obscure. Using cell-culture devices that simulated increased IFP conditions by
applying hydrostatic pressure (HP) ranging from 0 to 20 mm Hg to the cells, we
found that the elevated HPs increased the migration speeds, invasiveness, cell
volume, filopodial number and aquaporin-1 (AQP1), Snail and vinculin expression
levels, as well as phosphorylation of caveolin-1 and extracellular signal
regulated kinase1/2 (ERK1/2), in the lung cancer cells CL1-5 and A549. The
increases of migration speed and cell volume correlated temporally with the
increase of AQP1 expression. The elevated HP-induced migration acceleration was
hindered by AQP1 knockdown using small interfering RNA (siRNA) transfection.
Inhibition of ERK1/2 phosphorylation using the mitogen-activated protein kinase
kinase inhibitor PD98059 abrogated the elevated HP-induced AQP1 upregulation and
migration acceleration in the cancer cells. Caveolin-1 knockdown by siRNA
transfection attenuated the HP-induced, ERK1/2-depedent AQP1 upregulation and
migration acceleration. Further biochemical studies revealed that the caveolin-1
activation-driven ERK1/2 signaling is mediated by Akt1/2 phosphorylation. By
contrast, the elevated HPs had negligible effects on the migration speed and
volume of normal bronchial epithelial cells. These results disclose a novel
mechanism relating high IFP to the invasiveness of cancer cells and highlight
potential targets to impede cancer spreading.
PMID- 27499096
TI - Bill of Rights for Persons with Mental Illness.
PMID- 27499097
TI - PIN1 in hepatocellular carcinoma is associated with TP53 gene status.
AB - Phosphorylation of proteins on serine/threonine residues that precede proline
(pSer/Thr-Pro) is specifically catalyzed by the peptidyl-prolyl cis-trans
isomerase PIN1. PIN1-mediated prolyl-isomerization induces cell cycle arrest and
growth inhibition through the regulation of target proteins, including TP53. We
examined whether PIN1 acts in a different manner according to TP53 gene status in
hepatocellular carcinoma (HCC). We investigated the expression of PIN1 and TP53
proteins in 119 HCC tissue samples. We also analyzed PIN1 expression in
combination with TP53 gene mutation and its correlation with the clinical
outcome. In addition, we used synthetic small interfering RNA to silence PIN1
gene expression in TP53 wild-type and TP53 mutant HCC cell lines, and then
evaluated cell proliferation, migration and invasion. Expression of PIN1 was
strongly associated with expression of TP53 protein or TP53 mutation of HCC
samples. PIN1 and TP53 expression in TP53 mutant HCC cell lines was higher than
that in TP53 wild-type HCC cell lines. Silencing of PIN1 in HLE cells containing
mutant TP53 significantly decreased cell proliferation, migration and invasion.
In contrast to PIN1 silencing in HLE cells, PIN1 silencing in HepG2 cells
containing functional wild-type TP53 resulted in enhanced tumor cell
proliferation. HCC patients bearing PIN1 expression with wild-type TP53 were
predicted to demonstrate favorable relapse-free survival. Our results suggest
that PIN1 plays a role in cancer cell proliferation, migration and invasion in a
different manner according to the TP53 gene mutation status in HCC. In
particular, interaction of PIN1 with mutant TP53 can act as a tumor promoter and
increase its oncogenic activities in HCC.
PMID- 27499098
TI - The influence of social category cues on the happy categorisation advantage
depends on expression valence.
AB - Facial race and sex cues can influence the magnitude of the happy categorisation
advantage. It has been proposed that implicit race or sex based evaluations drive
this influence. Within this account a uniform influence of social category cues
on the happy categorisation advantage should be observed for all negative
expressions. Support has been shown with angry and sad expressions but evidence
to the contrary has been found for fearful expressions. To determine the
generality of the evaluative congruence account, participants categorised
happiness with either sadness, fear, or surprise displayed on White male as well
as White female, Black male, or Black female faces across three experiments.
Faster categorisation of happy than negative expressions was observed for female
faces when presented among White male faces, and for White male faces when
presented among Black male faces. These results support the evaluative congruence
account when both positive and negative expressions are presented.
PMID- 27499099
TI - CD44 correlates with clinicopathological characteristics and is upregulated by
EGFR in breast cancer.
AB - Cluster of differentiation 44 (CD44), a well-known transmembrane glycoprotein,
serves as a promoting factor in the carcinogenesis and progression of a variety
of neoplasms. Previous studies have demonstrated that aberrant expression of CD44
was associated with the initiation, invasion, metastasis, and therapy-resistance
of breast cancer, but whether there was any association between CD44 and
pathological characteristics of breast cancer or epidermal growth factor receptor
(EGFR) has not been clearly elucidated. In this study, we utilized public
microarray data analysis and tissue microarray technologies to display that CD44
level was enhanced in breast cancer and was significantly correlated with
histological grade and the status of estrogen receptor, progesterone receptor and
human epidermal growth factor receptor-2 (HER2) and EGFR. Furthermore, mRNA
expression of CD44 in breast tumors was positively correlated with basal
cytokeratin markers KRT5 and KRT17, but inversely associated with luminal marker
FOXA1. Besides, Kaplan-Meier analysis showed that high CD44 mRNA level had
adverse impact on the progression-free survival of patients with HER2-expressing
or basal-like breast cancer. Functionally, inhibition of EGFR activity by
erlotinib impaired the invasion and migration ability of breast cancer cell
lines. Western blot assays demonstrated that erlotinib treatment decreased the
expression of CD44, accompanied with the reduced protein levels of mesenchymal
and cancer stem cell markers. Collectively, this study suggested that the
expression of CD44 was upregulated by EGFR pathway and CD44 had a robust impact
on the development of breast cancer.
PMID- 27499100
TI - Single-walled carbon nanotube-loaded doxorubicin and Gd-DTPA for targeted drug
delivery and magnetic resonance imaging.
AB - An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon
nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be
loaded with the anticancer drug doxorubicin (DOX) and magnetic resonance imaging
(MRI) contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA).
This DOX- and Gd-DTPA-loaded NGR functionalized SWCNTs (DOX/NGR-SWCNTs/Gd-DPTA)
retained both cytotoxicity of DOX and MRI contrast effect of Gd-DPTA. This drug
delivery system showed excellent stability in physiological solutions. This
DOX/NGR-SWCNTs/Gd-DPTA system could accumulate in tumors and enter into tumor
cells, which facilitated combination chemotherapy with diagnosis of tumor in one
system. An excellent in vitro anti-tumor effect was shown in MCF-7 cells treated
by DOX/NGR-SWCNTs/Gd-DPTA, compared with DOX solution, DOX/SWCNTs and
DOX/SWCNTs/Gd-DPTA. In vivo data of DOX/NGR-SWCNTs/Gd-DPTA group in tumor-bearing
mice further confirmed that this system performed much higher tumor targeting
capacity and anti-tumor efficacy than other control groups.
PMID- 27499101
TI - Use of potassium titanyl phosphate (KTP) laser Dermastat in the treatment of
recurrent anterior epistaxis - a new technique.
AB - OBJECTIVE: To evaluate the short- to medium-term effectiveness of potassium
titanyl phosphate (KTP) laser Dermastat in patients with recurrent anterior
epistaxis. METHOD: Fifty-eight patients presenting with recurrent anterior
epistaxis were treated using potassium titanyl phosphate laser Dermastat. Those
with recurrent epistaxis arising from prominent vessels in Little's area, and/or
those for whom treatment with silver nitrate cautery failed, were included. The
main outcome measure was resolution of epistaxis at two months. RESULTS: Fifty
eight patients were treated; 27 were under 18 years old. Thirty patients had
prominent vessels. Thirty-one patients had undergone previous cautery treatment.
Thirty-eight patients had treatment to the left side, 19 to the right and 1 to
both. At two months, 74 per cent reported resolution of epistaxis with no
complications. This increased to 78 per cent at further follow up. CONCLUSION:
Our technique is a successful, safe treatment for recurrent anterior epistaxis in
an otherwise treatment-resistant group. A single procedure is effective. The
handpiece and tip are reusable and sterilisable, resulting in cost-effectiveness.
PMID- 27499102
TI - "MedTRIS" (Medical Triage and Registration Informatics System): A Web-based
Client Server System for the Registration of Patients Being Treated in First Aid
Posts at Public Events and Mass Gatherings.
AB - First aid (FA) services are provisioned on-site as a preventive measure at most
public events. In Flanders, Belgium, the Belgian Red Cross-Flanders (BRCF) is the
major provider of these FA services with volunteers being deployed at
approximately 10,000 public events annually. The BRCF has systematically
registered information on the patients being treated in FA posts at major events
and mass gatherings during the last 10 years. This information has been collected
in a web-based client server system called "MedTRIS" (Medical Triage and
Registration Informatics System). MedTRIS contains data on more than 200,000
patients at 335 mass events. This report describes the MedTRIS architecture, the
data collected, and how the system operates in the field. This database
consolidates different types of information with regards to FA interventions in a
standardized way for a variety of public events. MedTRIS allows close monitoring
in "real time" of the situation at mass gatherings and immediate intervention,
when necessary; allows more accurate prediction of resources needed; allows to
validate conceptual and predictive models for medical resources at (mass) public
events; and can contribute to the definition of a standardized minimum data set
(MDS) for mass-gathering health research and evaluation. Gogaert S , Vande
veegaete A , Scholliers A , Vandekerckhove P . "MedTRIS" (Medical Triage and
Registration Informatics System): a web-based client server system for the
registration of patients being treated in first aid posts at public events and
mass gatherings. Prehosp Disaster Med. 2016;31(5):557-562.
PMID- 27499103
TI - Preliminary investigation of five novel long non-coding RNAs in hepatocellular
carcinoma cell lines.
AB - Hepatocellular carcinoma (HCC) is a highly prevalent cancer with a high mortality
rate and HCC is always accompanied with a hepatitis B virus (HBV) infection,
unlike many other types of cancers. Over the past few years, cancer-related long
non-coding RNAs (lncRNAs) and virus-related lncRNAs have attracted the attention
of many researchers, and a number of previous studies have examined the
relationship between lncRNAs and various cancers and viruses. The current study
used The Cancer Genome Atlas database to screen for lncRNAs up-regulated in HCC
in order to identify cancer biomarkers. Results revealed five lncRNAs that were
the most up-regulated. This result was then verified in 10 HCC cell lines and two
normal liver cell lines. Quantitative real-time PCR revealed that the five
lncRNAs were substantially up-regulated in HCC cell lines. Several of the five
lncRNAs were expressed at higher levels in a few HCC cell lines that were
infected with HBV or that were positive for its protein or DNA than in HCC cell
lines that were not infected with HBV or that were negative for its protein or
DNA. These findings suggest that the five lncRNAs might play a role in the
progression of HCC and/or HBV infection, and these findings need to be studied in
further detail.
PMID- 27499104
TI - Assessment of the mean glandular dose using LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn
and Li2B4O7:Cu TL detectors in mammography radiation fields.
AB - The aim of this paper is the characterization of four thermoluminescence
detectors (TLD), namely, LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn and Li2B4O7:Cu for
the measurement of the entrance surface air kerma (ESAK) and estimation of the
mean glandular dose (MGD) in digital mammography examinations at hospitals and
clinics. Low-energy x-ray beams in the typical energy ranges of mammography,
produced with a tungsten target and additional 60 um molybdenum filtration were
implemented and characterized at the Laboratory of Metrology of Ionizing
Radiation at Instituto Superior Tecnico. These beams were used for the
characterization of the TLDs in terms of sensitivity, linearity, reproducibility,
energy dependence and fading at 40 degrees C. The energy dependence test was
further extended using clinical beams produced by mammography units at hospitals
and clinics. The method proposed by the International Atomic Energy Agency was
used for the measurement of ESAK and assessment of MGD. The combined standard
uncertainty for the measurement of ESAK (and MGD) was determined in accordance to
the Guide to the expression of uncertainty in measurement. The x-ray beams
generated in the 23-40 kVp range presented HVL values from 0.36 to 0.46 mm Al.
The beam produced at 28 kVp (HVL 0.39 mm Al) was considered as reference. The
radiation field defined a circle with 84 mm diameter with a maximum variation of
the beam intensity of less than 1% at the top flat (plateau) within 4 cm of the
central axis. The estimated total uncertainty for the measurement of air kerma
was 0.42%. All the TL detectors tested showed good performance except the
commercial Li2B4O7:Mn (or TLD-800) which was excluded due to its poor sensitivity
in our experimental set up. Both lithium fluorides showed better linearity and
reproducibility as well as lower energy dependence and fading when compared to
lithium borates. The stable behaviour of LiF:Mg,Ti and LiF:Mg,Cu,P detectors is
reflected in the low combined standard uncertainty of +/-5.6% and +/-4.3%
respectively (or +/-5.1% and +/-3.6% if fading is neglected). In general a
total combined uncertainty lower than +/-10% for the measurement of ESAK was
obtained for the four TL materials studied.
PMID- 27499105
TI - Structural insight into beta-Clamp and its interaction with DNA Ligase in
Helicobacter pylori.
AB - Helicobacter pylori, a gram-negative and microaerophilic bacterium, is the major
cause of chronic gastritis, gastric ulcers and gastric cancer. Owing to its
central role, DNA replication machinery has emerged as a prime target for the
development of antimicrobial drugs. Here, we report 2A structure of beta-clamp
from H. pylori (Hpbeta-clamp), which is one of the critical components of DNA
polymerase III. Despite of similarity in the overall fold of eubacterial beta
clamp structures, some distinct features in DNA interacting loops exists that
have not been reported previously. The in silico prediction identified the
potential binders of beta-clamp such as alpha subunit of DNA pol III and DNA
ligase with identification of beta-clamp binding regions in them and validated by
SPR studies. Hpbeta-clamp interacts with DNA ligase in micromolar binding
affinity. Moreover, we have successfully determined the co-crystal structure of
beta-clamp with peptide from DNA ligase (not reported earlier in prokaryotes)
revealing the region from ligase that interacts with beta-clamp.
PMID- 27499106
TI - Mycobacterium oryzae sp. nov., a scotochromogenic, rapidly growing species is
able to infect human macrophage cell line.
AB - Gram-stain-positive, acid-fast-positive, rapidly growing, rod-shaped bacteria
(designated as strains JC290T, JC430 and JC431) were isolated from paddy
cultivated soils on the Western Ghats of India. Phylogenetic analysis placed the
three strains among the rapidly growing mycobacteria, being most closely related
to Mycobacterium tokaiense 47503T (98.8 % 16S rRNA gene sequence similarity),
Mycobacterium murale MA112/96T (98.8 %) and a few other Mycobacterium species.
The level of DNA-DNA reassociation of the three strains with M. tokaiense DSM
44635T was 23.4+/-4 % (26.1+/-3 %, reciprocal analysis) and 21.4+/-2 % (22.1+/-4
%, reciprocal analysis). The three novel strains shared >99.9 % 16S rRNA gene
sequence similarity and DNA-DNA reassociation values >85 %. Furthermore,
phylogenetic analysis based on concatenated sequences (3071 bp) of four
housekeeping genes (16S rRNA, hsp65, rpoB and sodA) revealed that strain JC290T
is clearly distinct from all other Mycobacteriumspecies. The three strains had
diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol,
phosphatidylinositolmannosides, unidentified phospholipids, unidentified
glycolipids and an unidentified lipid as polar lipids. The predominant isoprenoid
quinone for all three strains was MK-9(H2). Fatty acids were C17 : 1omega7c, C16
: 0, C18 : 1omega9c, C16 : 1omega7c/C16 : 1omega6c and C19 : 1omega7c/C19 :
1omega6c for all the three strains. On the basis of phenotypic, chemotaxonomic
and phylogenetic data, it was concluded that strains JC290T, JC430 and JC431 are
members of a novel species within the genus Mycobacterium and for which the name
Mycobacterium oryzae sp. nov. is proposed. The type strain is JC290T (=KCTC
39560T=LMG 28809T).
PMID- 27499107
TI - Multi-residue determination of 210 drugs in pork by ultra-high-performance liquid
chromatography-tandem mass spectrometry.
AB - This paper presents a multi-residue analytical method for 210 drugs in pork using
ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry
(UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring
(MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included
macrolides, sulfonamides, tetracyclines, beta-lactams, beta-agonists,
aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic
hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal
drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides,
amides, alkaloids and others. A rapid and simple preparation method was applied
to process the animal tissues, including solvent extraction with an
acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The
recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20%
for spiked concentrations of 10, 50 and 250MUg/kg. More than 90% of the analytes
achieved low limits of quantification (LOQs)<10MUg/kg. The decision limit
(CCalpha), detection capability (CCbeta) values were in the range of 2-502MUg/kg
and 4-505MUg/kg, respectively. This method is significant for food safety
monitoring and controlling veterinary drug use.
PMID- 27499109
TI - Editorial overview: Vaccines: novel technologies for vaccine development.
PMID- 27499108
TI - Implementation of high slurry concentration and sonication to pack high
efficiency, meter-long capillary ultrahigh pressure liquid chromatography
columns.
AB - Slurry packing capillary columns for ultrahigh pressure liquid chromatography is
complicated by many interdependent experimental variables. Previous results have
suggested that combination of high slurry concentration and sonication during
packing would create homogeneous bed microstructures and yield highly efficient
capillary columns. Herein, the effect of sonication while packing very high
slurry concentrations is presented. A series of six, 1m*75MUm internal diameter
columns were packed with 200mg/mL slurries of 2.02MUm bridged-ethyl hybrid silica
particles. Three of the columns underwent sonication during packing and yielded
highly efficient separations with reduced plate heights as low as 1.05.
PMID- 27499110
TI - Driving with advanced vehicle technology: A qualitative investigation of older
drivers' perceptions and motivations for use.
AB - For older drivers, in-vehicle technology offers much potential to improve safety
and increase longevity of retaining both licensure and community mobility.
However, little is known about how older drivers perceive Advanced Vehicle
Technologies (AVTs) based on everyday driving experience. Interviews with 35
older drivers (20 men; 15 women) aged 60-85 who owned a vehicle with at least two
AVTs (e.g., back-up camera, lane departure warning) were conducted to explore the
meanings that older drivers assigned to AVTs and motivations for use, including
whether age-related functional changes were part of their automobile purchase
decision. Findings indicate that age-related changes are not a primary reason for
why older adults seek out AVTs, but they still perceived and experienced AVTs to
counteract age-related changes in driving performance based upon changes they
felt occurring within the body. Older drivers also described AVTs as generating a
sense of comfort behind-the-wheel. Comfort with this technology was equated with
convenience, ease of use, and increased feelings of safety. Discussion emphasizes
how assessments of the quality of driving performance and value of technology
occur in relation to an aging body.
PMID- 27499111
TI - Metastatic bone disease: A review of survival, prognostic factors and outcomes
following surgical treatment of the appendicular skeleton.
AB - Survival data and prognostic factors may help to provide insight when deciding on
the appropriate orthopaedic treatment for patients presenting with metastatic
bone disease. This review was conducted to look at the outcomes following
orthopaedic surgery for metastatic lesions in the extremities. The literature was
identified through the Medline and Embase database and further refined via a set
of inclusion and exclusion criteria. Overall, patients presenting with metastatic
bone disease from renal cell cancer or breast cancer had the longest survival
rate. Important factors found to predict prognosis was the presence of visceral
metastasis, multiple metastases, pathological fracture and the type of primary
tumour involved. These prognostic factors may help to direct future inquiry into
metastatic bone disease and help determine the type of surgery to use in a
metastatic setting in order to avoid complications and unnecessary revisions as
well as provide durability.
PMID- 27499112
TI - Novel Synthetic PEGylated Conjugate of alpha-Lipoic Acid and Tempol Reduces Cell
Death in a Neuronal PC12 Clonal Line Subjected to Ischemia.
AB - alpha-Lipoic acid (alpha-LA), a natural thiol antioxidant, and Tempol, a
synthetic free radical scavenger, are known to confer neuroprotection following
ischemic insults in both in vivo and in vitro models. The aim of this study was
to synthesize and characterize a conjugate of alpha-LA and Tempol linked by
polyethylene glycol (PEG) in order to generate a more efficacious neuroprotectant
molecule. AD3 (alpha-Tempol ester-omega-lipo ester PEG) was synthesized,
purified, and characterized by flash chromatography and reverse phase high
pressure liquid chromatography and by 1H nuclear magnetic resonance, infrared
spectroscopy, and mass spectrometry. AD3 conferred neuroprotection in a PC12
pheochromocytoma cell line of dopaminergic origin, exposed to oxygen and glucose
deprivation (OGD) insult measured by LDH release. AD3 exhibited EC50 at 10 MUM
and showed a 2-3-fold higher efficacy compared to the precursor moieties,
indicating an intrinsic potent neuroprotective activity. AD3 attenuated by 25%
the intracellular redox potential, by 54% lipid peroxidation and prevented
phosphorylation of ERK, JNK, and p38 by 57%, 22%, and 21%, respectively.
Cumulatively, these findings indicate that AD3 is a novel conjugate that confers
neuroprotection by attenuation of MAPK phosphorylation and by modulation of the
redox potential of the cells.
PMID- 27499113
TI - Self-organized centripetal movement of corneal epithelium in the absence of
external cues.
AB - Maintaining the structure of the cornea is essential for high-quality vision. In
adult mammals, corneal epithelial cells emanate from stem cells in the limbus,
driven by an unknown mechanism towards the centre of the cornea as cohesive
clonal groups. Here we use complementary mathematical and biological models to
show that corneal epithelial cells can self-organize into a cohesive, centripetal
growth pattern in the absence of external physiological cues. Three conditions
are required: a circumferential location of stem cells, a limited number of cell
divisions and mobility in response to population pressure. We have used these
complementary models to provide explanations for the increased rate of
centripetal migration caused by wounding and the potential for stem cell leakage
to account for stable transplants derived from central corneal tissue, despite
the predominantly limbal location of stem cells.
PMID- 27499114
TI - Does the type of sagittal spinal shape influence the clinical results of lumbar
disc arthroplasty?
AB - INTRODUCTION: It has been suggested that the indication for lumbar total disc
replacement (LTDR) takes into account the local parameters, such as the type of
disc disease demonstrated on MRI and the presence or absence of facet joint
osteoarthritis. The type of preoperative sagittal curvature could also be taken
into account. This study reports the clinical results of LTDRs depending on the
type of sagittal spinal alignment. MATERIAL AND METHODS: Eighty patients were
included in this prospective study, with a mean age of 41.7years (range, 27
56years). The clinical analysis took into account the lumbar VAS, the Oswestry
Disability Index (ODI), and the preoperative frequency of painkiller use, at
1year and at the last follow-up. The satisfaction index, return to work, and
willingness to undergo the same treatment were also collected. The radiological
study included the analysis of lumbar-pelvic parameters to distribute the
patients according to the Roussouly classification. RESULTS: The mean follow-up
was 59.1months (range, 14-96months). The type 1 group included four cases.
Reduction of the VAS, the ODI score, and the frequency of painkiller use at the
last follow-up were significant in type 2 and 3 patients, and non-significant for
type 4. Eighty-five percent of type 2 patients and 87.5% of type 3 patients were
satisfied or very satisfied with the surgery versus only 68% of the type 4
patients. In addition, 63% of the type 4 patients declared they would be willing
to undergo the same treatment again versus 85% of the type 2 patients and 82.5%
of the type 3 patients. It should also be noted that 67% of the patients in this
series returned to work. DISCUSSION AND CONCLUSION: This study underscores the
influence of the type of sagittal curvature on the clinical results of LTDR, with
type 4 patients showing inferior clinical results because of a higher rate of
residual lower back pain. The indication in LTDR should be reconsidered for
discogenic lower back pain in type 4 patients.
PMID- 27499115
TI - Pre- and postoperative complications of adult forearm fractures treated with
plate fixation.
AB - INTRODUCTION: Adult forearm fractures account for 1-2% of all fractures of the
limbs. The main objective of this retrospective multicenter study was to evaluate
pre- and postoperative complications of forearm fractures. The secondary
objective was to evaluate functional and radiological results of plate
osteosynthesis for these fractures. MATERIAL AND METHODS: Between January 2008
and March 2014, 131 forearm fractures were reviewed retrospectively. Fractures
were classified preoperatively according to the AO classification. Clinical
outcomes were classified into four categories according to the Tschnerne and
Oestern classification. Pre- and postoperative complications were sought
systematically. RESULTS: Before surgery, 12 patients had neurological impairment
(9%). At the last follow-up, nine patients had persistent neurological disorders
(6.9%). Union of forearm fractures was obtained in 122 patients at 4.6 months on
average (+/-2.6). Nine patients with nonunion were observed (6.9%) and five
patients had radioulnar synostosis (3.8%). DISCUSSION: The frequency of
neurological complications concomitant to forearm fractures is noteworthy.
Similar cases with essentially irritative neurological disease have been reported
in the literature, in particular for the ulnar nerve. Fracture nonunion is a
relatively common complication: between 2 and 10% of cases depending on the
study. LEVEL OF EVIDENCE: IV.
PMID- 27499116
TI - Reply to the Letter by Siamak Sabour, Fariba Ghassemi.
PMID- 27499117
TI - Subscapularis and deltoid preserving anterior approach for reverse shoulder
arthroplasty.
AB - HYPOTHESIS: We hypothesize that performing a RSA using an anterior approach
without cutting the subscapularis tendon and the deltoid muscle could provide
patients with superior short-term clinical outcomes and immediate active range of
motion (ROM) without immobilization. METHODS: Between August 2013 and June 2015,
all patients who had a primary RSA were considered potentially eligible for
inclusion in this prospective study. RESULTS: No immediate intra- or
postoperative complications were noted. A statistically significant improvement
of VAS (from 6.7 to 1; P<.001), SANE (from 34 to 80; P<.001), and elevation (from
103 degrees to 128 degrees ; P=.02) was observed. In some cases, patients who
had pseudoparalysis preoperative were able to achieve full anterior elevation few
days after the operation. DISCUSSION: Using a subscapularis and deltoid
preserving anterior approach is an option for patients requiring RSA. Leaving
this tendon intact and preserving the deltoid minimize the need for immediate
postoperative immobilization and allow for faster recovery of shoulder ROM,
without risking the concern of humeral anterior dislocation. Overall duration of
hospital stay as well as length of postoperative physical therapy may be
minimized, with substantial long-term economic gain. Longer follow-up and
comparison with standard approaches is necessary in the future. LEVEL OF EVIDENCE
OF THE STUDY: Level IV, case series with no comparative group.
PMID- 27499118
TI - Inhibitory effect of metformin combined with gemcitabine on pancreatic cancer
cells in vitro and in vivo.
AB - Pancreatic cancer is a malignant digestive system tumor with a particularly poor
prognosis, and is the fourth leading cause of cancer-associated mortality in the
USA. The anti-diabetic therapeutic agent, metformin (MET) has been demonstrated
to exert anti-tumor effects. The present study assessed the ability of MET, alone
or in combination with gemcitabine (GEM), to inhibit the growth of the human
CFPAC-1 pancreatic cancer cell line in vitro and in vivo. Cell counting kit-8
assays were performed to measure CFPAC-1 cell viability and apoptosis was
detected with annexin V/propidium iodide. Cell cycle analysis was conducted by
flow cytometry. The mRNA and protein levels of B-cell lymphoma-extra large (Bcl
xL), Bcl2 associated X protein (Bax), caspase-3, survivin and cyclin D1 in CFPAC
1 cells and tumor tissues were detected by reverse transcription-polymerase chain
reaction and western blotting, respectively. Furthermore, the expression levels
of caspase-3 and proliferating cell nuclear antigen in tumor tissues were
detected by immunohistochemistry. The results demonstrated that following MET
treatment, the growth of CFPAC-1 cells and xenografts in nude mice was inhibited,
the expression levels of Bcl-xL, survivin and cyclin D1 were downregulated, while
the expression levels of Bax and caspase-3 were upregulated. These effects were
enhanced when MET was administered in combination with GEM. The mechanism
underlying the anti-tumor effect of MET may be associated with the induction of
cell apoptosis and the inhibition of proliferation.
PMID- 27499119
TI - CSF hypotension: A review of its manifestations, investigation and management.
AB - Intracranial cerebrospinal fluid (CSF) hypotension usually arises in the context
of known or suspected leak of CSF. This can be spontaneous, or due to central
nervous system trauma or dural defects created during lumbar puncture or epidural
anaesthesia. Spontaneous intracranial hypotension (SIH) is increasingly being
recognised as a cause for orthostatic headache or spontaneous subdural haematoma
where no other obvious cause is found. We review CSF physiology, the mechanism of
symptom generation in CSF hypotension and the investigation and management of the
syndrome. Whilst commonly mild and self-limiting, CSF hypotension may result in
life threatening complications and is most often treatable. When the syndrome is
severe, prolonged or complicated, epidural blood patching (EBP) is the mainstay
of treatment.
PMID- 27499120
TI - Striatal silent lacunar infarction is associated with changes to the substantia
nigra in patients with early-stage Parkinson's disease: A diffusion kurtosis
imaging study.
AB - A recent study has shown that striatal silent infarction may occur secondary to
the degeneration of dopaminergic neurons in the substantia nigra (SN) of mice.
However, it is uncertain whether this phenomenon occurs in patients with early
stage Parkinson's disease (PD) and can be detected by diffusion kurtosis imaging
(DKI). A total of 72 untreated patients with early-stage PD underwent
conventional MRI and DKI. Participants were divided into control and striatal
silent lacunar infarction (SSLI) groups. The differences in mean kurtosis (MK)
values of the SN, Hoehn-Yahr (H-Y) staging, and Unified Parkinson's Disease
Rating Scale (UPDRS) III score between groups, were analyzed. Linear regression
analysis was used to correlate age, SSLI count, silent lacunar infarction count
in other brain areas and age-related white matter change score with MK values of
the SN. Spearman correlation coefficient analysis was used to correlate MK values
of the SN and SSLI count with H-Y staging and UPDRS III score. There was no
significant difference in the severity of disease between two groups; however, MK
values of the SN with SSLI present were significantly higher than in SN without
SSLI. In addition, SSLI count had linear correlation with MK values of the SN,
which had positive correlation with H-Y-staging and UPDRS III score. SSLI is
associated with structural changes to the SN in patients with early-stage PD,
detectable by DKI, and may aggravate their motor impairments.
PMID- 27499121
TI - Transcortical selective amygdalohippocampectomy technique through the middle
temporal gyrus revisited: An anatomical study laboratory investigation.
AB - The anterior temporal lobectomy (ATL) and selective amygdalohippocampectomy
(SelAH) have been used for surgical treatment of mesial temporal lobe epilepsy.
We examined the comprehensive white matter tract anatomy of the temporal lobe to
gain an insight into the trans-middle temporal gyrus, a lateral approach which
has been commonly used. The transmiddle temporal gyrus approach was performed in
a stepwise manner on cadaveric human heads to examine the traversing white matter
pathways through it and the structures located in the temporal horn. We reviewed
the literature to compare the trans-middle temporal gyrus approach with other
SelAH techniques based on surgical outcomes. There does not appear to be a
significant difference in seizure outcome between SelAH and ATL. However, the
SelAH provides a better neuropsychological outcomes than the ATL in selected
patients. Each SelAH approach has individual advantages and disadvantages. Based
on our anatomical study, in the transcortical amygdalohippocampectomy technique
through the middle temporal gyrus the white matter pathways to be encountered. In
the temporal horn, the collateral eminence, hippocampus, lateral ventricular
sulcus, choroidal fissure, inferior choroidal point, choroid plexus, fimbria of
the fornix, and amygdala are exposed. The subpial dissection is performed along
the lateral ventricular sulcus from the collateral eminence on lateral side and
from the choroidal fissure on medial side by microdissector for en bloc resection
of the hippocampus proper. The trans-middle temporal gyrus approach is commonly
used in treatment of mesial temporal lobe epilepsy patients. A better anatomical
and functional understanding of the structures of the temporal lobe is crucial
for safer and more accurate surgery.
PMID- 27499122
TI - Complications following cranioplasty and relationship to timing: A systematic
review and meta-analysis.
AB - The optimal timing of cranioplasty after decompressive craniectomy has not been
well established. The purpose of this study was to evaluate the relationship
between timing of cranioplasty and related complications. A systematic search of
MEDLINE, Scopus, and the Cochrane databases was performed using PRISMA guidelines
for English-language articles published between 1990 and 2015. Case series, case
control and cohort studies, and clinical trials reporting timing and complication
data for cranioplasty after decompressive craniectomy in adults were included.
Extracted data included overall complications, infections, reoperations,
intracranial hemorrhage, extra-axial fluid collections, hydrocephalus, seizures,
and bone resorption for cranioplasty performed within (early) and beyond (late)
90days. Twenty-five of 321 articles met inclusion criteria for a total of 3126
patients (1421 early vs. 1705 late). All were retrospective observational
studies. Early cranioplasty had significantly higher odds of hydrocephalus than
late cranioplasty (Odds Ratio [OR] 2.38, 95% Confidence Interval [CI] 1.25-4.52,
p=0.008). There was no difference in odds of overall complications, infections,
reoperations, intracranial hemorrhage, extra-axial fluid collections, seizures,
or bone resorption. Subgroup analysis of trauma patients revealed a decreased
odds of extra-axial fluid collection (OR 0.30, p=0.02) and an increased odds of
hydrocephalus (OR 4.99, p=0.05). Early cranioplasty within 90days after
decompressive craniectomy is associated with an increased odds of hydrocephalus
than with later cranioplasty, but no difference in odds of developing other
complications. Earlier cranioplasty in the trauma population is associated with
fewer extra-axial fluid collections.
PMID- 27499123
TI - Objective Detection of Oral Carcinoma with Multispectral Fluorescence Lifetime
Imaging In Vivo.
AB - Successful early detection and demarcation of oral carcinoma can greatly impact
the associated morbidity and mortality rates. Current methods for detection of
oral cancer include comprehensive visual examination of the oral cavity,
typically followed by tissue biopsy. A noninvasive means to guide the clinician
in making a more objective and informed decision toward tissue biopsy can
potentially improve the diagnostic yield of this process. To this end, we
investigate the potential of fluorescence lifetime imaging (FLIM) for objective
detection of oral carcinoma in the hamster cheek pouch model of oral
carcinogenesis in vivo. We report that systematically selected FLIM features can
differentiate between low-risk (normal, benign and low-grade dysplasia) and high
risk (high-grade dysplasia and cancer) oral lesions with sensitivity and
specificity of 87.26% and 93.96%, respectively. We also show the ability of FLIM
to generate "disease" maps of the tissue which can be used to evaluate relative
risk of neoplasia. The results demonstrate the potential of multispectral FLIM
with objective image analysis as a noninvasive tool to guide comprehensive oral
examination.
PMID- 27499124
TI - Serpentinicella alkaliphila gen. nov., sp. nov., a novel alkaliphilic anaerobic
bacterium isolated from the serpentinite-hosted Prony hydrothermal field, New
Caledonia.
AB - A novel anaerobic, alkaliphilic, Gram-stain-positive, spore-forming bacterium was
isolated from a carbonaceous hydrothermal chimney in Prony Bay, New Caledonia.
This bacterium, designated strain 3bT, grew at temperatures from 30 to 43
degrees C (optimum 37 degrees C) and at pH between 7.8 and 10.1 (optimum 9.5).
Added NaCl was not required for growth (optimum 0-0.2 %, w/v), but was tolerated
at up to 4 %. Yeast extract was required for growth. Strain 3bT utilized
crotonate, lactate and pyruvate, but not sugars. Crotonate was dismutated to
acetate and butyrate. Lactate was disproportionated to acetate and propionate.
Pyruvate was degraded to acetate plus trace amounts of hydrogen. Growth on
lactate was improved by the addition of fumarate, which was used as an electron
acceptor and converted to succinate. Sulfate, thiosulfate, elemental sulfur,
sulfite, nitrate, nitrite, FeCl3, Fe(III)-citrate, Fe(III)-EDTA, chromate,
arsenate, selenate and DMSO were not used as terminal electron acceptors. The G+C
content of the genomic DNA was 33.2 mol%. Phylogenetic analysis based on the 16S
rRNA gene sequence indicated that the isolate is a member of the family
Clostridiaceae, order Clostridiales within the phylum Firmicutes. Strain 3bT was
most closely related to 'Alkaliphilus hydrothermalis' FatMR1T (92.2 % 16S rRNA
gene sequence similarity), and was positioned approximately equidistantly between
the genera Alkaliphilus, Anaerovirgula and Natronincola. On the basis of
phylogenetic, genetic, chemotaxonomic and physiological properties, strain 3bT is
proposed to represent a novel species of a new genus, for which the name
Serpentinicella alkaliphila gen. nov., sp. nov. is proposed. The type strain of
Serpentinicella alkaliphila is 3bT (=DSM 100013T=JCM 30645T).
PMID- 27499126
TI - Formulation, characterisation and in vivo evaluation of lipid-based nanocarrier
for topical delivery of diflunisal.
AB - Diflunisal (DIF) is non-steroidal anti-inflammatory drug used in the treatment of
rheumatoid arthritis, osteoarthritis. The current engrossment was aimed at
formulation and assessment of DIF-loaded solid lipid nanoparticles (SLNs) for
topical/dermal application. SLNs formulated by hot homogenisation method based on
microemulsification technique were spherical with a mean size of 124.0 +/- 2.07
nm; PDI 0.294 +/- 0.15. The cumulative amount permeated/area was 109.99 +/- 0.008
MUg/cm(2), along with permeation flux (6.30 +/- 0.09 MUg/cm(2)/h) and skin
retention (11.74 +/- 0.155 MUg/cm(2)) across mice skin. The SLNs of DIF showed
significant decrease in fluid volume, granuloma tissue weight, leukocyte
count/mm(3) after application of SLN formulation in mice air pouch model.
Similarly, in mice ear oedema and rat paw oedema model, there was 2.30 and 1.29
time increase in percentage inhibition of oedema after SLN formulation
application, respectively, as compared with conventional cream. Hence, the SLNs
of DIF may prove to be a potential nanocarrier to effectively treat the local
inflammatory conditions associated with arthritis.
PMID- 27499125
TI - Schistosome sex matters: a deep view into gonad-specific and pairing-dependent
transcriptomes reveals a complex gender interplay.
AB - As a key event for maintaining life cycles, reproduction is a central part of
platyhelminth biology. In case of parasitic platyhelminths, reproductive
processes can also contribute to pathology. One representative example is the
trematode Schistosoma, which causes schistosomiasis, an infectious disease, whose
pathology is associated with egg production. Among the outstanding features of
schistosomes is their dioecious lifestyle and the pairing-dependent
differentiation of the female gonads which finally leads to egg synthesis. To
analyze the reproductive biology of Schistosoma mansoni in-depth we isolated
complete ovaries and testes from paired and unpaired schistosomes for comparative
RNA-seq analyses. Of >7,000 transcripts found in the gonads, 243 (testes) and
3,600 (ovaries) occurred pairing-dependently. Besides the detection of genes
transcribed preferentially or specifically in the gonads of both genders, we
uncovered pairing-induced processes within the gonads including stem cell
associated and neural functions. Comparisons to work on neuropeptidergic
signaling in planarian showed interesting parallels but also remarkable
differences and highlights the importance of the nervous system for flatworm
gonad differentiation. Finally, we postulated first functional hints for 235
hypothetical genes. Together, these results elucidate key aspects of flatworm
reproductive biology and will be relevant for basic as well as applied,
exploitable research aspects.
PMID- 27499127
TI - Generation of a Chiral Giant Micelle.
AB - Over the past few years, chiral supramolecular assemblies have been successfully
used for recognition, sensing and enantioselective transformations. Several
approaches are available to control chirality of discrete assemblies (e.g., cages
and capsules), but few are efficient in assuring chirality for micellar
aggregates. Optically active amino acid-derived surfactants are commonly used to
generate chiral spherical micelles. To circumvent this limitation, we benefited
from the uniaxial growth of spherical micelles into long cylindrical micelles
usually called wormlike or giant micelles, upon the addition of cosolutes. This
paper describes the unprecedented formation of chiral giant micelles in aqueous
solutions of cetyltrimethylammonium bromide (CTAB) upon increasing addition of
enantiopure sodium salt of 1,1'-bi-2-naphthol (Na-binaphtholate) as a cosolute.
Depending on the concentrations of CTAB and Na-binaphtholate, chiral gel-like
systems are obtained. The transition from spherical to giant micellar structures
was probed using rheology, cryo-transmission electron microscopy, polarimetry,
and electronic circular dichroism (CD). CD can be effectively used to monitor the
incorporation of Na-binaphtholate into the micelle palisade as well as to
determine its transition to giant micellar structures. Our approach expands the
scope for chirality induction in micellar aggregates bringing the possibility to
generate "smart" chiral systems and an alternative asymmetric chiral environment
to perform enantioselective transformations.
PMID- 27499128
TI - Cell division cycle associated 1 as a novel prognostic biomarker and therapeutic
target for oral cancer.
AB - Oral cavity carcinoma (OCC) is one of the most common causes of cancer-related
death worldwide and has poor clinical outcome after standard therapies.
Therefore, new prognostic biomarkers and therapeutic targets for OCC are urgently
needed. We selected cell division cycle associated 1 (CDCA1) as a candidate OCC
biomarker. Immunohistochemical analysis confirmed that CDCA1 protein was
expressed in 67 of 99 OCC tissues (67.7%), but not in healthy oral epithelia.
CDCA1 expression was significantly associated with poor prognosis in OCC patients
(P=0.0244). Knockdown of CDCA1 by siRNAs significantly increased apoptosis of
tumor cells. These data suggest that CDCA1 represents a novel prognostic
biomarker and therapeutic target for OCC.
PMID- 27499129
TI - Paraburkholderiapallidirosea sp. nov., isolated from a monsoon evergreen broad
leaved forest soil.
AB - A Gram-stain-negative, rod-shaped, aerobic and motile bacterial strain, DHOK13T,
was isolated from the forest soils of Dinghushan Biosphere Reserve, Guangdong
Province, PR China (112 degrees 31' E, 23 degrees 10' N). It grew optimally at
28-33 degrees C and pH 7.0-7.5. The main fatty acids were C16 : 0, C17 : 0
cyclo, C19 : 0 cycloomega8c, summed feature 2 (C12 : 0 aldehyde and/or unknown
10.9525) and summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c). The
organism contained ubiquinone Q-8 as the predominant isoprenoid quinone. The
total DNA G+C content of strain DHOK13T was 62.0 mol%. Phylogenetic analysis of
the 16S rRNA gene, as well as the sequence of the partial housekeeping genes,
gyrB and recA, showed consistently that strain DHOK13T formed an independent
cluster with Paraburkholderia phenazinium LMG 2247T. DNA-DNA hybridization
studies showed relatively low relatedness values (39 %) of strain DHOK13T with P.
phenazinium LMG 2247T. The phenotypic, chemotaxonomic and phylogenetic data
showed that strain DHOK13T represents a novel species of the genus
Paraburkholderia for which the name Paraburkholderia pallidirosea sp. nov. is
proposed. The type strain is DHOK13T (=KCTC 42626T=LMG 28846T).
PMID- 27499130
TI - Time-varying coefficient vector autoregressions model based on dynamic
correlation with an application to crude oil and stock markets.
AB - This paper proposes a new time-varying coefficient vector autoregressions (VAR)
model, in which the coefficient is a linear function of dynamic lagged
correlation. The proposed model allows for flexibility in choices of dynamic
correlation models (e.g. dynamic conditional correlation generalized
autoregressive conditional heteroskedasticity (GARCH) models, Markov-switching
GARCH models and multivariate stochastic volatility models), which indicates that
it can describe many types of time-varying causal effects. Time-varying causal
relations between West Texas Intermediate (WTI) crude oil and the US Standard and
Poor's 500 (S&P 500) stock markets are examined by the proposed model. The
empirical results show that their causal relations evolve with time and display
complex characters. Both positive and negative causal effects of the WTI on the
S&P 500 in the subperiods have been found and confirmed by the traditional VAR
models. Similar results have been obtained in the causal effects of S&P 500 on
WTI. In addition, the proposed model outperforms the traditional VAR model.
PMID- 27499131
TI - Emissions and temperature benefits: The role of wind power in China.
AB - BACKGROUND: As a non-fossil technology, wind power has an enormous advantage over
coal because of its role in climate change mitigation. Therefore, it is important
to investigate how substituting wind power for coal-fired electricity will affect
emission reductions, changes in radiative forcing and rising temperatures,
particularly in the context of emission limits. METHODS: We developed an
integrated methodology that includes two parts: an energy-economy-environmental
(3E) integrated model and an emission-temperature response model. The former is
used to simulate the dynamic relationships between economic output, wind energy
and greenhouse gas (GHG) emissions; the latter is used to evaluate changes in
radiative forcing and warming. RESULTS: Under the present development projection,
wind energy cannot serve as a major force in curbing emissions, even under the
strictest space-restraining scenario. China's temperature contribution to global
warming will be up to 21.76% if warming is limited to 2 degrees. With the wind
for-coal power substitution, the corresponding contribution to global radiative
forcing increase and temperature rise will decrease by up to 10% and 6.57%,
respectively. CONCLUSIONS: Substituting wind power for coal-fired electricity has
positive effects on emission reductions and warming control. However, wind energy
alone is insufficient for climate change mitigation. It forms an important
component of the renewable energy portfolio used to combat global warming.
PMID- 27499132
TI - The Stepwise Increase in the Number of Transcription Factor Families in the
Precambrian Predated the Diversification of Plants On Land.
AB - The colonization of the land by streptophytes and their subsequent radiation is a
major event in Earth history. We report a stepwise increase in the number of
transcription factor (TF) families and subfamilies in Archaeplastida before the
colonization of the land. The subsequent increase in TF number on land was
through duplication within existing TF families and subfamilies. Almost all
subfamilies of the Homeodomain (HD) and basic Helix-Loop-Helix (bHLH) had evolved
before the radiation of extant land plant lineages from a common ancestor. We
demonstrate that the evolution of these TF families independently followed
similar trends in both plants and metazoans; almost all extant HD and bHLH
subfamilies were present in the first land plants and in the last common ancestor
of bilaterians. These findings reveal that the majority of innovation in plant
and metazoan TF families occurred in the Precambrian before the Phanerozoic
radiation of land plants and metazoans.
PMID- 27499133
TI - Characterization of the Poplar Pan-Genome by Genome-Wide Identification of
Structural Variation.
AB - Many recent studies have emphasized the important role of structural variation
(SV) in determining human genetic and phenotypic variation. In plants, studies
aimed at elucidating the extent of SV are still in their infancy. Evidence has
indicated a high presence and an active role of SV in driving plant genome
evolution in different plant species.With the aim of characterizing the size and
the composition of the poplar pan-genome, we performed a genome-wide analysis of
structural variation in three intercrossable poplar species: Populus nigra,
Populus deltoides, and Populus trichocarpa We detected a total of 7,889 deletions
and 10,586 insertions relative to the P. trichocarpa reference genome, covering
respectively 33.2 Mb and 62.9 Mb of genomic sequence, and 3,230 genes affected by
copy number variation (CNV). The majority of the detected variants are inter
specific in agreement with a recent origin following separation of
species.Insertions and deletions (INDELs) were preferentially located in low-gene
density regions of the poplar genome and were, for the majority, associated with
the activity of transposable elements. Genes affected by SV showed lower-than
average expression levels and higher levels of dN/dS, suggesting that they are
subject to relaxed selective pressure or correspond to pseudogenes.Functional
annotation of genes affected by INDELs showed over-representation of categories
associated with transposable elements activity, while genes affected by genic
CNVs showed enrichment in categories related to resistance to stress and
pathogens. This study provides a genome-wide catalogue of SV and the first
insight on functional and structural properties of the poplar pan-genome.
PMID- 27499134
TI - Metabolomic analysis of CSF indicates brain metabolic impairment precedes
hematological indices of anemia in the iron-deficient infant monkey.
AB - OBJECTIVES: Iron deficiency (ID) anemia leads to long-term neurodevelopmental
deficits by altering iron-dependent brain metabolism. The objective of the study
was to determine if ID induces metabolomic abnormalities in the cerebrospinal
fluid (CSF) in the pre-anemic stage and to ascertain the aspects of abnormal
brain metabolism affected. METHODS: Standard hematological parameters [hemoglobin
(Hgb), mean corpuscular volume (MCV), transferrin (Tf) saturation, and zinc
protoporphyrin/heme (ZnPP/H)] were compared at 2, 4, 6, 8, and 12 months in iron
sufficient (IS; n = 7) and iron-deficient (ID; n = 7) infant rhesus monkeys. Five
CSF metabolite ratios were determined at 4, 8, and 12 months using 1H NMR
spectroscopy at 16.4 T and compared between groups and in relation to hematologic
parameters. RESULTS: ID infants developed ID (Tf saturation < 25%) by 4 months of
age and all became anemic (Hgb < 110 g/L and MCV < 60 fL) at 6 months. Their heme
indices normalized by 12 months. Pyruvate/glutamine and phosphocreatine/creatine
(PCr/Cr) ratios in CSF were lower in the ID infants by 4 months (P < 0.05). The
PCr/Cr ratio remained lower at 8 months (P = 0.02). ZnPP/H, an established blood
marker of pre-anemic ID, was positively correlated with the CSF citrate/glutamine
ratio (marginal correlation, 0.34; P < 0.001; family wise error rate = 0.001).
DISCUSSION: Metabolomic analysis of the CSF is sensitive for detecting the
effects of pre-anemic ID on brain energy metabolism. Persistence of a lower
PCr/Cr ratio at 8 months, even as hematological measures demonstrated recovery
from anemia, indicate that the restoration of brain energy metabolism is delayed.
Metabolomic platforms offer a useful tool for early detection of the impact of ID
on brain metabolism in infants.
PMID- 27499135
TI - Rapid discovery and identification of anti-inflammatory constituents from
traditional Chinese medicine formula by activity index, LC-MS, and NMR.
AB - The traditional activity-guided approach has the shortcoming of low accuracy and
efficiency in discovering active compounds from TCM. In this work, an approach
was developed by integrating activity index (AI), liquid chromatography - mass
spectrometry (LC-MS), and nuclear magnetic resonance (NMR) to rapidly predict and
identify the potential active constituents from TCM. This approach was used to
discover and identify the anti-inflammatory constituents from a TCM formula, Gui
Zhi-Jia-Shao-Yao-Tang (GZJSYT). The AI results indicated that, among the 903
constituents detected in GZJSYT by LC-MS, 61 constituents with higher AI values
were very likely to have anti-inflammatory activities. And eight potential active
constituents of them were isolated and validated to have significant inhibitory
effects against NO production on LPS-induced RAW 264.7 cell model. Among them,
glycyrrhisoflavone (836), glisoflavanone (893) and isoangustone A (902) were
reported to have anti-inflammatory effects for the first time. The proposed
approach could be generally applicable for rapid and high efficient discovery of
anti-inflammatory constituents from other TCM formulae or natural products.
PMID- 27499136
TI - HOX gene expression predicts response to BCL-2 inhibition in acute myeloid
leukemia.
AB - Inhibitors of B-cell lymphoma-2 (BCL-2) such as venetoclax (ABT-199) and
navitoclax (ABT-263) are clinically explored in several cancer types, including
acute myeloid leukemia (AML), to selectively induce apoptosis in cancer cells. To
identify robust biomarkers for BCL-2 inhibitor sensitivity, we evaluated the ex
vivo sensitivity of fresh leukemic cells from 73 diagnosed and
relapsed/refractory AML patients, and then comprehensively assessed whether the
responses correlated to specific mutations or gene expression signatures.
Compared with samples from healthy donor controls (nonsensitive) and chronic
lymphocytic leukemia (CLL) patients (highly sensitive), AML samples exhibited
variable responses to BCL-2 inhibition. Strongest CLL-like responses were
observed in 15% of the AML patient samples, whereas 32% were resistant, and the
remaining exhibited intermediate responses to venetoclax. BCL-2 inhibitor
sensitivity was associated with genetic aberrations in chromatin modifiers, WT1
and IDH1/IDH2. A striking selective overexpression of specific HOXA and HOXB gene
transcripts were detected in highly BCL-2 inhibitor sensitive samples. Ex vivo
responses to venetoclax showed significant inverse correlation to beta2
microglobulin expression and to a lesser degree to BCL-XL and BAX expression. As
new therapy options for AML are urgently needed, the specific HOX gene expression
pattern can potentially be used as a biomarker to identify venetoclax-sensitive
AML patients for clinical trials.
PMID- 27499137
TI - The novel PI3K-delta inhibitor TGR-1202 enhances Brentuximab Vedotin-induced
Hodgkin lymphoma cell death via mitotic arrest.
PMID- 27499138
TI - Rictor has a pivotal role in maintaining quiescence as well as stemness of
leukemia stem cells in MLL-driven leukemia.
AB - Little is known about the roles of Rictor/mTORC2 in the leukemogenesis of acute
myeloid leukemia. Here, we demonstrated that Rictor is essential for the
maintenance of mixed lineage leukemia (MLL)-driven leukemia by preventing
leukemia stem cells (LSCs) from exhaustion. Rictor depletion led to a reactive
activation of mTORC1 signaling by facilitating the assembly of mTORC1.
Hyperactivated mTORC1 signaling in turn drove LSCs into cycling, compromised the
quiescence of LSCs and eventually exhausted their capacity to generate leukemia.
At the same time, loss of Rictor had led to a reactive activation of FoxO3a in
leukemia cells, which acts as negative feedback to restrain greater over
reactivation of mTORC1 activity and paradoxically protects leukemia cells from
exhaustion. Simultaneous depletion of Rictor and FoxO3a enabled rapid exhaustion
of MLL LSCs and a quick eradication of MLL leukemia. As such, our present
findings highlighted a pivotal regulatory axis of Rictor-FoxO3a in maintaining
quiescence and the stemness of LSCs.
PMID- 27499139
TI - Human memory B cells.
AB - A key feature of the adaptive immune system is the generation of memory B and T
cells and long-lived plasma cells, providing protective immunity against
recurring infectious agents. Memory B cells are generated in germinal center (GC)
reactions in the course of T cell-dependent immune responses and are
distinguished from naive B cells by an increased lifespan, faster and stronger
response to stimulation and expression of somatically mutated and affinity
matured immunoglobulin (Ig) genes. Approximately 40% of human B cells in adults
are memory B cells, and several subsets were identified. Besides IgG+ and IgA+
memory B cells, ~50% of peripheral blood memory B cells express IgM with or
without IgD. Further smaller subpopulations have additionally been described.
These various subsets share typical memory B cell features, but likely also
fulfill distinct functions. IgM memory B cells appear to have the propensity for
refined adaptation upon restimulation in additional GC reactions, whereas
reactivated IgG B cells rather differentiate directly into plasma cells. The
human memory B-cell pool is characterized by (sometimes amazingly large) clonal
expansions, often showing extensive intraclonal IgV gene diversity. Moreover,
memory B-cell clones are frequently composed of members of various subsets,
showing that from a single GC B-cell clone a variety of memory B cells with
distinct functions is generated. Thus, the human memory B-cell compartment is
highly diverse and flexible. Several B-cell malignancies display features
suggesting a derivation from memory B cells. This includes a subset of chronic
lymphocytic leukemia, hairy cell leukemia and marginal zone lymphomas. The
exposure of memory B cells to oncogenic events during their generation in the GC,
the longevity of these B cells and the ease to activate them may be key
determinants for their malignant transformation.
PMID- 27499140
TI - Anti-CD44 antibodies inhibit both mTORC1 and mTORC2: a new rationale supporting
CD44-induced AML differentiation therapy.
PMID- 27499141
TI - Emended description of Mycobacterium abscessus, Mycobacterium abscessus subsp.
abscessus and Mycobacteriumabscessus subsp. bolletii and designation of
Mycobacteriumabscessus subsp. massiliense comb. nov.
AB - The taxonomic position of members of the Mycobacterium abscessus complex has been
the subject of intensive investigation and, in some aspects confusion, in recent
years as a result of varying approaches to genetic data interpretation.
Currently, the former species Mycobacterium massiliense and Mycobacterium
bolletii are grouped together as Mycobacterium abscessus subsp. bolletii. They
differ greatly, however, as the former M. bolletii has a functional erm(41) gene
that confers inducible resistance to macrolides, the primary therapeutic
antimicrobials for M. abscessus, while in the former M. massiliense the erm(41)
gene is non-functional. Furthermore, previous whole genome studies of the M.
abscessus group support the separation of M. bolletii and M. massiliense. To shed
further light on the population structure of Mycobacterium abscessus, 43 strains
and three genomes retrieved from GenBank were subjected to pairwise comparisons
using three computational approaches: verage ucleotide dentity, enome to enome
istance and single nucleotide polymorphism analysis. The three methods produced
overlapping results, each demonstrating three clusters of strains corresponding
to the same number of taxonomic entities. The distances were insufficient to
warrant distinction at the species level, but met the criteria for
differentiation at the subspecies level. Based on prior erm(41)-related
phenotypic data and current genomic data, we conclude that the species M.
abscessus encompasses, in adjunct to the presently recognized subspecies M.
abscessus subsp. abscessus and M. abscessus subsp. bolletii, a third subspecies
for which we suggest the name M. abscessus subsp. massiliense comb. nov. (type
strain CCUG 48898T=CIP 108297T=DSM 45103T=KCTC 19086T).
PMID- 27499142
TI - Use of video-based education and tele-health home monitoring after liver
transplantation: Results of a novel pilot study.
AB - BACKGROUND: In this observational study, we analyzed the feasibility and early
results of a perioperative, video-based educational program and tele-health home
monitoring model on postoperative care management and readmissions for patients
undergoing liver transplantation. METHODS: Twenty consecutive liver
transplantation recipients were provided with tele-health home monitoring and an
educational video program during the perioperative period. Vital statistics were
tracked and monitored daily with emphasis placed on readings outside of the
normal range (threshold violations). Additionally, responses to effectiveness
questionnaires were collected retrospectively for analysis. RESULTS: In the
study, 19 of the 20 patients responded to the effectiveness questionnaire, with
95% reporting having watched all 10 videos, 68% watching some more than once, and
100% finding them effective in improving their preparedness for understanding
their postoperative care. Among these 20 patients, there was an observed 19%
threshold violation rate for systolic blood pressure, 6% threshold violation rate
for mean blood glucose concentrations, and 8% threshold violation rate for mean
weights. This subset of patients had a 90-day readmission rate of 30%.
CONCLUSION: This observational study demonstrates that tele-health home
monitoring and video-based educational programs are feasible in liver
transplantation recipients and seem to be effective in enhancing the monitoring
of vital statistics postoperatively. These data suggest that smart technology is
effective in creating a greater awareness and understanding of how to manage
postoperative care after liver transplantation.
PMID- 27499143
TI - Discussion.
PMID- 27499144
TI - Cancer surgeons' attitudes and practices about discussing the chance of operative
"cure".
AB - BACKGROUND: While physician attitudes about treatment goals have been examined
around end-of-life care, surgeon attitudes regarding communication of therapeutic
goals prior to cancer-directed operations have not been investigated. We examined
how surgeons discuss the potential for cancer "cure" prior to operative treatment
and how surgeons perceive patient priorities and treatment goals. METHODS:
Surgeons were invited to complete a Web-based survey about attitudes and
practices when discussing cancer-directed operations, including how they defined
cancer cure and whether and how they discussed cure as a treatment goal. RESULTS:
A total of 551 e-mail invitations were sent and opened; 205 responses were
received (response rate 37.2%). While 44.9% of surgeons reported being asked
about cure in all or most discussions, only 37.6% used the word cure as often.
When discussing cure, an equal number of surgeons reported using qualitative
versus quantitative language to express probability of cure (45.7% and 47.4%,
respectively). Roughly one third of surgeons (n = 65, 31.7%) defined cure as 5
year, disease-free survival; 36.1% (n = 74) defined cure as absence of recurrence
over the patient's lifetime; and 21 (10.2%) defined cure as return to baseline
population risk for that specific cancer. Over half of surgeons (n = 112, 56.9%)
perceived that to "be cured" was among the top 2 priorities of patients
presenting for operative treatment. CONCLUSION: When discussing relative benefits
and goals of therapy, surgeon self-reported discussions of cure varied
considerably. Despite identifying cure as a top priority for patients, surgeons
were not inclined to incorporate cure into discussions of risks, benefits, and
goals of therapy.
PMID- 27499145
TI - Prioritizing qualitative research in surgery: A synthesis and analysis of
publication trends.
AB - BACKGROUND: Over the past 2 decades, researchers have recognized the value of
qualitative research. Little has been done to characterize its application to
surgery. We describe characteristics and overall prevalence of qualitative
surgical research. METHODS: We searched PubMed and CINAHL using "surgery" and 7
qualitative methodology terms. Four researchers extracted information; a fifth
researcher reviewed 10% of abstracts for inter-rater reliability. RESULTS: A
total of 3,112 articles were reviewed. Removing duplicates, 28% were relevant (N
= 878; kappa = 0.70). Common qualitative methodologies included phenomenology
(34.3%) and grounded theory (30.2%). Interviews were the most common data
collection method (81.9%) of patients (64%) within surgical oncology (15.4%).
Postdischarge was the most commonly studied topic (30.8%). Overall, 41% of
studies were published in nursing journals, while 8% were published in surgical
journals. More than half of studies were published since 2011. CONCLUSION:
Results suggest qualitative surgical research is gaining popularity. Most is
published in nonsurgical journals, however, utilizing only 2 methodologies
(phenomenology, grounded theory). The surgical journals that have published
qualitative research had study topics restricted to a handful of surgical
specialties. Additional surgical qualitative research should take advantage of a
greater variety of approaches to provide insight into rare phenomena and social
context.
PMID- 27499146
TI - Discussion.
PMID- 27499147
TI - Delayed interventions and mortality in trauma damage control laparotomy.
AB - BACKGROUND: In damage control laparotomy, operative principles include hemorrhage
and contamination control. However, required components of initial damage control
laparotomy are unknown, and nonemergency injury repair is sometimes delayed for
resuscitation, angiography, or nonabdominal operations. The frequency and effects
of delayed interventions are unknown. METHODS: A retrospective review of patients
undergoing damage control laparotomy at a single, urban trauma center was
performed. Interventions initially performed at the second laparotomy were
considered delayed interventions. RESULTS: In the study, 330 damage control
laparotomy patients survived to reoperation. Of all interventions, 13.9% were
first performed at the second laparotomy, including 11.9% of visceral
interventions and 27.2% of vascular interventions. Overall, 29.7% of patients
underwent an unplanned re-exploration, and 21.8% of patients underwent re
exploration for hemorrhage control. There was no significant increase in
mortality (33.3% vs 23.9%, P = .09), intra-abdominal infection (37.9% vs 28.0%; P
= .10), anastomotic leak (8.0% vs 5.8%, P = .45), or enterocutaneous fistula
formation (9.2% vs 9.1%, P = 1.00) with delayed interventions overall. However,
mortality was increased in patients undergoing delayed vascular interventions
(59.1% vs 22.8%, P = .003), unplanned re-exploration (45.9% vs 18.1%, P < .001)
and re-exploration for hemorrhage control (50.0% vs 19.8%, P < .001). CONCLUSION:
Delayed interventions are common in damage control laparotomy, with abdominal
interventions often spread over multiple explorations. Mortality is increased in
patients undergoing emergent re-exploration and with delayed repair of major
vascular injuries. Ideal treatment of damage control laparotomy patients may
include addressing injuries more completely at the first laparotomy instead of
deferring care for other priorities.
PMID- 27499148
TI - Achieving low anastomotic leak rates utilizing clinical perfusion assessment.
AB - BACKGROUND: Anastomotic leak after colorectal resection increases morbidity,
mortality, and in the setting of cancer, increases recurrences rates and reduces
survival odds. Recent reports suggest that fluorescence evaluation of perfusion
after colorectal anastomosis creation is associated with low anastomotic leak
rates (1.4%). The purpose of this work was to evaluate whether a similar low
anastomotic leak rate after left-sided colorectal resections could be achieved
using standard assessment of blood flow to the bowel ends. METHODS: We performed
a retrospective chart review at an academic tertiary referral center, evaluating
317 consecutive patients who underwent a pelvic anastomosis after sigmoid
colectomy, left colectomy, or low anterior resection. All operations were
performed by a single surgeon from March 2008 to January 2015 with only standard
clinical measures used to assess perfusion to the bowel ends. The primary outcome
measure was the anastomotic leak rate as diagnosed by clinical symptoms, exam, or
routine imaging. RESULTS: The average patient age was 59.7 years with an average
body mass index of 28.8 kg/m(2). Rectal cancer (128, 40.4%) was the most common
indication for operation while hypertension (134, 42.3%) was the most common
comorbidity. In total, 177 operations were laparoscopic (55.8%), 13 were
reoperative resections (4.1%), and 108 were protected with a loop ileostomy
(34.1%). Preoperative chemotherapy was administered to 25 patients (7.9%) while
preoperative chemo/radiation was administered to 64 patients (20.2%). The
anastomotic leak rate was 1.6% (5/317). CONCLUSION: Our data suggests that
standard, careful evaluation of adequate blood flow via inspection and
confirmation of pulsatile blood flow to the bowel ends and meticulous
construction of the colorectal or coloanal anastomoses can result in very low
leak rates, similar to the rate reported when intraoperative imaging is used to
assess perfusion.
PMID- 27499149
TI - Diborane-Mediated Deoxygenation of o-Nitrostyrenes To Form Indoles.
AB - A mild, transition metal-free, diborane-mediated deoxygenation of nitro groups
was discovered that in situ generates nitrosoarene reactive intermediates. This
new reactivity mode of B2pin2 was leveraged to construct indoles from o
nitrostyrenes through a reductive-cyclization reaction that exhibits a Hammett
rho-value of +0.97 relative to sigmapara values. Our new deoxygenation reaction
is efficient, practical, and scaleable, enabling access to a broad range of
indoles.
PMID- 27499150
TI - Is there an influence of hepatic steatosis on fibrosis and necroinflammation in
young patients with chronic viral hepatitis B?
AB - OBJECTIVES: Our aim was to investigate the association of liver fibrosis and
necroinflammation with HS in untreated young patients with chronic hepatitis B
(CHB). MATERIALS AND METHODS: A retrospective study was conducted in a military
hospital in Turkey. A total of 254 subjects with CHB were included in this study.
These subjects were divided into two groups: group 1 consisted of patients with
hepatic steatosis (HS) according to ultrasonography (USG) and group 2 consisted
of non-HS subjects. Sociodemographic, biochemical, histopathological, virological
and USG results were recorded for both groups retrospectively. Statistical
analysis was performed using SPSS 22.0. RESULTS: The prevalence of HS was found
to be 11.4%. A significant statistical difference was found between group 1 and
group 2 regarding the fibrosis degree (p = 0.045). No statistically significant
difference was noted between two groups for age, levels of ALT, AST, HBeAg, HBV
DNA levels, HAI scores, diagnosis age and duration of CHB. No difference was
noted between the grade of HS and variables. A positive correlation was found
between fibrosis groups and the grade of HS (p = 0.012, r = 0.158) and between
HAI groups and the grade of HS (p = 0.029, r = 0.137). CONCLUSION: The prevalence
of steatosis was not higher in patients with CHB. HS is associated with advanced
hepatic fibrosis, but not viral liver disease.
PMID- 27499151
TI - OTUD7B and NIK expression in non-small cell lung cancer: Association with
clinicopathological features and prognostic implications.
AB - PURPOSE: To investigate the correlation among OTUD7B and NIK expression and the
clinicopathological characteristics in NSCLC patients. METHODS: One hundred and
twenty patients were involved in this study. We detected OTUD7B and NIK
expression by immunohistochemistry and analyzed their correlation with
clinicopathological data. RESULTS: The expression of OTUD7B and NIK were
negatively correlated in NSCLC tumor samples (rs=-0.421, P<0.001). The higher
expression of OTUD7B was associated with smaller tumor size(P=0.018), less lymph
node metastasis (P=0.012) and earlier TNM stage(P=0.039), while the higher
expression of NIK was only related to more lymph node metastasis(P=0.031) and
later TNM stage(P=0.011). MMP-9 was negatively correlated with OTUD7B and
positively correlated with NIK. In addition, the high expression of OTUD7B was
associated with good prognosis of NSCLC patients (log-rank=6.714, P=0.0096), and
a high OTUD7B/low NIK index can predict an even better prognosis (log
rank=11.794, P=0.0006). Moreover, the multivariate Cox regression analysis showed
that OTUD7B rather than NIK is an independent marker of overall survival in NSCLC
patients(HR=1.602, 95% CI 1.009-2.544, P=0.046). CONCLUSIONS: OTUD7B and NIK may
play important roles in the development of lung cancer. The combination of OTUD7B
and NIK expression may be a good index for predicting the prognosis of NSCLC.
PMID- 27499152
TI - Distinctive interrelation of p53 with SCO2, COX, and TIGAR in human gastric
cancer.
AB - PURPOSE: p53, widely known as a tumor-suppressing gene, has recently been
reported to regulate glucose metabolism in human cancers through the synthesis of
cytochrome c oxidase 2 (SCO2), cytochrome c oxidase complex (COX), and TP53
induced glycolysis and apoptosis regulator (TIGAR). In this study, we
investigated the interrelations of the aforementioned proteins, particularly in
human gastric cancer, with cancer progression, other clinicopathological
parameters, and patient outcomes. MATERIALS AND METHODS: One hundred and ten
cases of primary gastric cancer occurring from June 2006 to June 2009 were
investigated and classified into two groups according to the intensity of
immunohistochemical staining for p53, SCO2, COX, and TIGAR. The
clinicopathological data were organized and analyzed based on electronic medical
records. RESULTS: In accordance with previous reports, the expression of p53
showed an inverse correlation with the expression of TIGAR (p=0.032) in gastric
cancer cells. However, the expression of SCO2 and COX were not shown to be
associated with the regulatory role of p53, unlike TIGAR expression.
Nevertheless, a significantly high recurrence rate was found in a patient group
with high COX expression (p=0.012). CONCLUSIONS: This study demonstrated that a
high p53 expression could be associated with the promotion of glycolysis in
gastric cancer via the modulation of TIGAR expression. In addition, a high COX
expression appeared to be interrelated with poor prognosis of gastric cancer.
However, further studies regarding the underlying molecular interactions are
required to provide more evidence to propose a novel mechanism that explains our
findings in gastric cancer.
PMID- 27499153
TI - Orbital meningeal melanocytoma: Histological, immunohistochemical and molecular
characterization of a case and review of the literature.
AB - AIMS: We provide morphological, immunohistochemical and molecular
characterization of the 3rd "intermediate-grade" orbital meningeal melanocytoma,
testing for the first time Vysis Melanoma FISH Probe Kit. We reviewed the
literature in order to discuss the main differential diagnoses and to provide a
better molecular description of these unusual tumors of difficult diagnosis and
controversial management. METHODS: Histochemical stains (Haematoxylin and Eosin,
Perls, reticulin), immunohistochemistry (HMB45, p16, Melan-A, S100, EMA, Ki67,
CD68), polymerase chain reaction amplification and sequence analysis (BRAF, exon
15; NRAS exons 2 and 3; c-KIT, exons 11, 13, 17, 18; GNAQ, exons 4 and 5; GNA11,
exons 4 and 5) and fluorescent in situ hybridization (RREB1, 6p25; MYB, 6q23;
CCND1, 11q13; CEP 6, 6p11.1-q11.1) were performed on paraffin-embedded, formalin
fixed material. RESULTS: Histological diagnosis of "intermediate-grade"
melanocytoma was supported by zonal necrosis and increased Ki67-index (12%).
Immunophenotype: HMB45+(strong, >75%), Melan-A+(strong, >75%), p16+(~20%), S100
/+ (<5%), EMA -/+ (<5%), CD68 - (positive histiocytes). No gene mutations nor
copy-number alterations were identified. The patient was asymptomatic and disease
free 3 years after total surgical excision. CONCLUSIONS: Adequate sampling and
accurate immunohistochemical characterization are important for a correct
diagnosis. Molecular analysis could provide important additional information
(especially for "intermediate-grade" tumors), but further data are needed.
PMID- 27499154
TI - Distribution pattern of Ki67 immunoreactivity in ductal intraepithelial
neoplasia: Correlation with lesion grade and potential utility.
AB - BACKGROUND: In this study, the pattern of distribution of the nuclei
immunoreactive with Ki67 was examined in DIN1c (DCIS, grade 1/low grade), DIN2
(DCIS, grade 2/intermediate grade), and DIN3 (DCIS, grade 3/high grade). The
lesions were evaluated to determine if distinctive patterns could be identified
in correlation with lesion grade. METHODS: Fifty seven (n=57) consecutive DIN
cases were investigated. Of these, 15 qualified as DIN1c, 28 as DIN2 and 14 as
DIN3. The patterns of distribution were recorded for each case as either
basal/peripheral or haphazard within the epithelial proliferation. RESULTS: There
was a statistically significant difference between the DIN1c, DIN2 and DIN3 in
terms of basal/peripheral versus haphazard distribution of Ki67 immunostaining
(Chi-square test, P<0.0001). Basal/peripheral staining pattern was dominant among
the DIN1c cases, while haphazard staining pattern was the dominant distribution
among the DIN3 cases. One half of the DIN2 cases showed basal/peripheral staining
pattern, while the other half showed a haphazard staining pattern. CONCLUSION:
High grade DIN lesions show haphazard Ki67 staining while low grade DIN lesions
show basal/peripheral Ki67 staining in the proliferating epithelial cells. This
feature could be practical in separating DIN lesions into low grade
(basal/peripheral-Ki67) and high grade (haphazard-Ki67) eliminating the grade
2/intermediate category.
PMID- 27499156
TI - Description of Altererythrobacter aerius sp. nov., isolated from air, and emended
description of the genus Altererythrobacter.
AB - A Gram-stain-negative, yellow-pigmented, ovoid to rod-shaped, strictly aerobic
bacterial strain, designated 100921-2T, was isolated from air at the foot of
Xiangshan Mountain. Phylogenetic and phenotypic analysis of the organism revealed
that the isolate belongs to the genus Altererythrobacter. Strain 100921-2T showed
high 16S rRNA gene sequence similarity (96.01-94.70 %) to other type strains of
the genus Altererythrobacter, with the highest similarity to
Altererythrobactermarensis MSW-14T. Growth of strain 100921-2T was observed at 4
50 degrees C (optimum, 30 degrees C), at pH 4.5-10.0 (optimum, pH 7.0) and at
salinities of 0-10 % (w/v) NaCl (optimum 0-0.5 %). The major fatty acids were C18
: 1omega7c (27.8 %), C17 : 1omega6c (23.1 %), 11-methyl C18 : 1omega7c(11.9 %),
summed feature 3 (9.1 %) and C15 : 0 2-OH (7.9 %). The predominant respiratory
quinone was ubiquinone-10 (Q-10). Polar lipid analysis indicated the presence of
diphosphatidylglycerol, sphingoglycolipid, phosphatidylethanolamine,
phosphatidylglycerol, phosphatidylcholine, two unknown phospholipids, five
unknown polar lipids and two unknown glycolipids. The DNA G+C content of the type
strain was 67.5 mol%. On the basis of the data from the polyphasic
characterization, strain 100921-2T represents a novel species, for which the name
Altererythrobacter aerius sp. nov. is proposed. The type strain is 100921-2T
(=CFCC 14287T=KCTC 42844T).
PMID- 27499155
TI - Genetic markers of pigmentation are novel risk loci for uveal melanoma.
AB - While the role of genetic risk factors in the etiology of uveal melanoma (UM) has
been strongly suggested, the genetic susceptibility to UM is currently vastly
unexplored. Due to shared epidemiological risk factors between cutaneous melanoma
(CM) and UM, in this study we have selected 28 SNPs identified as risk variants
in previous genome-wide association studies on CM or CM-related host phenotypes
(such as pigmentation and eye color) and tested them for association with UM
risk. By logistic regression analysis of 272 UM cases and 1782 controls using an
additive model, we identified five variants significantly associated with UM
risk, all passing adjustment for multiple testing. The three most significantly
associated variants rs12913832 (OR = 0.529, 95% CI 0.415-0.673; p = 8.47E-08),
rs1129038 (OR = 0.533, 95% CI 0.419-0.678; p = 1.19E-07) and rs916977 (OR =
0.465, 95% CI 0.339-0.637; p = 3.04E-07) are correlated (r(2) > 0.5) and map at
15q12 in the region of HERC2/OCA2, which determines eye-color in the human
population. Our data provides first evidence that the genetic factors associated
with pigmentation traits are risk loci of UM susceptibility.
PMID- 27499158
TI - Driving electrocatalytic activity by interface electronic structure control in a
metalloprotein hybrid catalyst for efficient hydrogen evolution.
AB - The rational design of metalloprotein hybrid structures and precise calculations
for understanding the role of the interfacial electronic structure in regulating
the HER activity of water splitting sites and their microscopic effect for
obtaining robust hydrogen evolution possess great promise for developing highly
efficient nano-bio hybrid HER catalysts. Here, we employ high-accuracy linear
scaling density functional theory calculations using a near-complete basis set
and a minimal parameter implicit solvent model within the self-consistent
calculations, on silver (Ag) ions assimilated on bacteriorhodopsin (bR) at
specific binding sites. Geometry optimization indicates the formation of active
sites at the interface of the metalloprotein complex and the density of states
reflects the metallic nature of the active sites. The reduced value of the
canonical orbital gap indicates the state of dynamic nature after Ag ion
assimilation on active sites and smooth electron transfer. These incorporated
active protein sites are more efficient in electrolytic splitting of water than
pristine sites due to their low value of Gibbs free energy for the HER in terms
of hydrogen coverages. Volcano plot analysis and the free energy diagram are
compared for understanding the hydrogen evolution efficiency. Moreover, the
essential role of the interfacial electronic properties in regulating the HER
catalytic activity of water splitting sites and enhancing the efficiency is
elucidated.
PMID- 27499157
TI - Conventional versus Drug-Eluting Bead Transarterial Chemoembolization for
Neuroendocrine Tumor Liver Metastases.
AB - PURPOSE: To compare outcomes of conventional transarterial chemoembolization with
drug-eluting bead (DEB) chemoembolization for treatment of neuroendocrine tumor
liver metastases. MATERIALS AND METHODS: This single-center, retrospective study
evaluated 177 transarterial chemoembolization treatments (78 conventional
chemoembolization treatments using ethiodized oil-based cisplatin, mitomycin C,
and doxorubicin and 99 DEB chemoembolization treatments using doxorubicin-loaded
100-300 MUm DEBs) from 2012 to 2015. Hepatic disease distribution was 93% bilobar
for both groups with largest lesion size 5.0 cm +/- 2.7. No difference was noted
in regard to lesion size or distribution, carcinoid syndrome, or pancreastatin
production. Clinical outcomes including complications; liver function tests
(LFTs); and radiologic (modified Response Evaluation Criteria in Solid Tumors),
biochemical (pancreastatin levels), and symptomatic responses were evaluated at 1
month follow-up. RESULTS: Higher symptomatic response (complete and partial) was
identified with conventional transarterial chemoembolization compared with DEB
chemoembolization (47% vs 30%; P < .05). Patients receiving DEB transarterial
chemoembolization experienced lower elevation of LFTs (aspartate
aminotransferase, 39 U/L vs 122 U/L; alanine aminotransferase, 20 U/L vs 93 U/L;
bilirubin, 0.001 mg/dL vs 0.123 mg/dL; P < .05) and less postembolization
syndrome (50% vs 67%; P < .05). Patients undergoing first-time DEB transarterial
chemoembolization had lower periprocedural octreotide maximum rate requirements
(58 MUg/h vs 66 MUg/h; P < .05). No difference was observed in biochemical (P =
.60) or radiologic (P < .20) responses. CONCLUSIONS: Conventional transarterial
chemoembolization yields better symptomatic response and may be preferred for
patients experiencing carcinoid symptoms. DEB transarterial chemoembolization,
with lower LFT elevations and postembolization syndrome incidence, may be
preferred for patients with poor liver function.
PMID- 27499159
TI - How flexible is a protein: simple estimates using FRET microscopy.
AB - Flexible proteins are frequently used to link subunits of larger complexes in
various contexts, for instance, in the construction of unimolecular sensors used
in FRET microscopy, and fusion proteins. How flexible such linkers are can be an
important question in the overall design of the complex, and yet sometimes
suprisingly difficult to establish. Such difficulties can arise because the
actual flexibility of a protein depends significantly on its interactions with
the solvent, and when the local environment is a subcellular compartment, even
the conditions of the solvent, may not be known. In this communication we propose
a simple numerical procedure through which the flexibility of such proteins can
be extracted from FRET based microscopy data.
PMID- 27499160
TI - Hypoxia upregulates Malat1 expression through a CaMKK/AMPK/HIF-1alpha axis.
AB - Increased expression levels of the long non-coding RNA metastasis-associated lung
adenocarcinoma transcript 1 (Malat1) have been associated with enhanced
proliferation and metastasis of several cancer cell types. Hypoxia, a hallmark
characteristic of solid tumors, has been linked to an increase in the activity of
the ATP-generating AMPK protein. Since Malat1 was recently shown to be
upregulated during hypoxia, the objective of this study was to determine the
contribution of AMPK in the mechanistic pathways regulating Malat1 expression in
low oxygen conditions. Compared to those cultured in 21% O2 conditions, HeLa
cells incubated in 1.5% O2 expressed more Malat1 transcripts. This observation
was mimicked in HEK293T cells using a synthetic reporter construct containing 5.6
kb of the human Malat1 promoter, suggesting that hypoxia directly impacted Malat1
gene transcription. Interestingly, pharmacological stimulation of AMPK increased
Malat1 promoter transactivation in 21% O2 conditions, whereas inhibition of
either AMPK or its upstream activator CaMKK completely abolished the augmentation
of Malat1 under hypoxia. Pharmacological modulation of LKB1, another major
regulator of AMPK, had no impact on Malat1 promoter transactivation, suggesting
that calcium inputs are important in the control of Malat1 expression by AMPK.
Overexpression of hypoxia-inducible factor-1alpha (HIF-1alpha) increased Malat1
expression in 21% O2 conditions, whereas pharmacological inhibition of HIF-1alpha
blocked the impact of hypoxia on the Malat1 promoter. Taken together, these
findings strongly suggest that Malat1 expression is regulated in hypoxic
conditions by a CaMKK/AMPK/HIF-1alpha axis. More research is needed in
physiological settings to test the clinical relevance of this pathway.
PMID- 27499161
TI - A Systematic Review of the Economic Evaluation of Telemedicine in Japan.
AB - OBJECTIVES: There is no systematic review on economic evaluations of telemedicine
in Japan, despite over 1000 trials implemented. Our systematic review aims to
examine whether Japan's telemedicine is cost-saving or cost-effective, examine
the methodological rigorousness of the economic evaluations, and discuss future
studies needed to improve telemedicine's financial sustainability. METHODS: We
searched five databases, including two Japanese databases, to find peer-reviewed
articles published between January 1, 2000 and December 31, 2014 in English and
Japanese that performed economic evaluations of Japan's telemedicine programs.
The methodological rigorousness of the economic analyses was assessed with a well
established checklist. We calculated the benefit-to-cost ratio (BCR) when a
reviewed study reported related data but did not report the BCR. All cost values
were adjusted to 2014 US dollars. RESULTS: Among the 17 articles identified, six
studies reported on settings connecting physicians for specialist consultations,
and eleven studies on settings connecting healthcare providers and patients at
home. There are three cost-benefit analyses and three cost-minimization analyses.
The remaining studies measured the benefit of telemedicine only, using medical
expenditure saved or users' willingness-to-pay. There was substantial diversity
in the methodological rigorousness. Studies on teledermatology and teleradiology
indicated a favorable level of economic efficiency. Studies on telehomecare gave
mixed results. One cost-benefit analysis on telehomecare indicated a low economic
efficiency, partly due to public subsidy rules, e.g., a too short budget period.
CONCLUSIONS: Overall, telemedicine programs in Japan were indicated to have a
favorable level of economic efficiency. However, the scarcity of the economic
literature indicates the need for further rigorous economic evaluation studies.
PMID- 27499162
TI - Helicobacter pylori Infection and Risk of Gastric Cancer in Korea: A Quantitative
Systematic Review.
AB - OBJECTIVES: In the context of the global decrease in mortality due to gastric
cancer, previous studies have reported that the effect of chronic Helicobacter
pylori (H. pylori) infection on the incidence of gastric cancer varies among
regions. This systematic review was conducted to investigate H. pylori as a risk
factor for gastric cancer in Korea, where the incidence of gastric cancer is
among the highest in the world. METHODS: A search strategy was established to
identify articles published in Korean as well as in English. Ultimately, we
included observational studies conducted among Korean patients that designed with
an age-matched and sex-matched control group that reported the odds ratio
associated with H. pylori. Gastric cancer cases were subdivided into overall
(OGC), cardia (CGC), non-cardia (NGC), early (EGC), advanced, intestinal (IGC),
and diffuse forms of gastric cancer. Summary odds ratios (SORs) with 95%
confidence intervals (CIs) were calculated in the meta-analysis using a random
effect model. RESULTS: Eleven case-control studies were ultimately selected. H.
pylori was associated with an SOR of 1.81 (95% CI, 1.29 to 2.54) for OGC.
Additionally, statistically significant risks were observed for CGC, NGC, EGC,
and IGC. CONCLUSIONS: Chronic H. pylori infection was found to raise the risk of
gastric cancer among Koreans, with the highest risk observed for CGC and EGC
(SOR=2.88 for both). Follow-up clinical epidemiologic studies are needed to
assess the effects of current treatments aimed at eradicating H. pylori
infections.
PMID- 27499163
TI - Short-term Effect of Fine Particulate Matter on Children's Hospital Admissions
and Emergency Department Visits for Asthma: A Systematic Review and Meta
analysis.
AB - OBJECTIVES: No children-specified review and meta-analysis paper about the short
term effect of fine particulate matter (PM2.5) on hospital admissions and
emergency department visits for asthma has been published. We calculated more
precise pooled effect estimates on this topic and evaluated the variation in
effect size according to the differences in study characteristics not considered
in previous studies. METHODS: Two authors each independently searched PubMed and
EMBASE for relevant studies in March, 2016. We conducted random effect meta
analyses and mixed-effect meta-regression analyses using retrieved summary effect
estimates and 95% confidence intervals (CIs) and some characteristics of selected
studies. The Egger's test and funnel plot were used to check publication bias.
All analyses were done using R version 3.1.3. RESULTS: We ultimately retrieved 26
time-series and case-crossover design studies about the short-term effect of
PM2.5 on children's hospital admissions and emergency department visits for
asthma. In the primary meta-analysis, children's hospital admissions and
emergency department visits for asthma were positively associated with a short
term 10 MUg/m3 increase in PM2.5 (relative risk, 1.048; 95% CI, 1.028 to 1.067;
I2=95.7%). We also found different effect coefficients by region; the value in
Asia was estimated to be lower than in North America or Europe. CONCLUSIONS: We
strengthened the evidence on the short-term effect of PM2.5 on children's
hospital admissions and emergency department visits for asthma. Further studies
from other regions outside North America and Europe regions are needed for more
generalizable evidence.
PMID- 27499164
TI - The Impact of Educational Status on 10-Year (2004-2014) Cardiovascular Disease
Prognosis and All-cause Mortality Among Acute Coronary Syndrome Patients in the
Greek Acute Coronary Syndrome (GREECS) Longitudinal Study.
AB - OBJECTIVES: The association between educational status and 10-year risk for acute
coronary syndrome (ACS) and all-cause mortality was evaluated. METHODS: From
October 2003 to September 2004, 2172 consecutive ACS patients from six Greek
hospitals were enrolled. In 2013 to 2014, a 10-year follow-up (2004-2014)
assessment was performed for 1918 participants (participation rate, 88%). Each
patient's educational status was classified as low (<9 years of school),
intermediate (9 to 14 years), or high (>14 years). RESULTS: Overall all-cause
mortality was almost twofold higher in the low-education group than in the
intermediate-education and high-education groups (40% vs. 22% and 19%,
respectively, p<0.001). Additionally, 10-year recurrent ACS events (fatal and non
fatal) were more common in the low-education group than in the intermediate
education and high-education groups (42% vs. 30% and 35%, p<0.001), and no
interactions between sex and education on the investigated outcomes were
observed. Moreover, patients in the high-education group were more physically
active, had a better financial status, and were less likely to have hypertension,
diabetes, or ACS than the participants with the least education (p<0.001);
however, when those characteristics and lifestyle habits were accounted for, no
moderating effects regarding the relationship of educational status with all
cause mortality and ACS events were observed. CONCLUSIONS: A U-shaped association
may be proposed for the relationship between ACS prognosis and educational
status, with participants in the low-education and high-education groups being
negatively affected by other factors (e.g., job stress, depression, or
loneliness). Public health policies should be aimed at specific social groups to
reduce the overall burden of cardiovascular disease morbidity.
PMID- 27499165
TI - The Effect of Geographic Units of Analysis on Measuring Geographic Variation in
Medical Services Utilization.
AB - OBJECTIVES: We aimed to evaluate the effect of geographic units of analysis on
measuring geographic variation in medical services utilization. For this purpose,
we compared geographic variations in the rates of eight major procedures in
administrative units (districts) and new areal units organized based on the
actual health care use of the population in Korea. METHODS: To compare geographic
variation in geographic units of analysis, we calculated the age-sex standardized
rates of eight major procedures (coronary artery bypass graft surgery,
percutaneous transluminal coronary angioplasty, surgery after hip fracture, knee
replacement surgery, caesarean section, hysterectomy, computed tomography scan,
and magnetic resonance imaging scan) from the National Health Insurance database
in Korea for the 2013 period. Using the coefficient of variation, the extremal
quotient, and the systematic component of variation, we measured geographic
variation for these eight procedures in districts and new areal units. RESULTS:
Compared with districts, new areal units showed a reduction in geographic
variation. Extremal quotients and inter-decile ratios for the eight procedures
were lower in new areal units. While the coefficient of variation was lower for
most procedures in new areal units, the pattern of change of the systematic
component of variation between districts and new areal units differed among
procedures. CONCLUSIONS: Geographic variation in medical service utilization
could vary according to the geographic unit of analysis. To determine how
geographic characteristics such as population size and number of geographic units
affect geographic variation, further studies are needed.
PMID- 27499166
TI - Food Security in Households of People Living With Human Immunodeficiency
Virus/Acquired Immunodeficiency Syndrome: A Cross-sectional Study in a
Subdivision of Darjeeling District, West Bengal.
AB - OBJECTIVES: Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome
(AIDS) adversely impacts food security in households of people living with
HIV/AIDS (PLWHA). Little research has focused on food insecurity among PLWHA in
India. The purpose of this study was to identify the prevalence of and factors
relating to food security in households of PLWHA in the Siliguri subdivision of
Darjeeling, West Bengal, India. METHODS: A cross-sectional community-based study
was carried out among 173 PLWHA residing in Siliguri and registered at the Anti
retroviral Therapy Centre of North Bengal Medical College & Hospital. Data was
collected at the household level with interviews of PLWHA using a food security
survey instrument. We analyzed the associations using logistic regression.
RESULTS: The prevalence of household food security among the participants was
50.9% (88/173). Five years or more of schooling, higher socioeconomic class and
males were found to be significantly associated with a higher likelihood of food
security. A later stage of the disease and the presence of other family members
with HIV/AIDS were significantly associated with a lower likelihood of food
security. The major coping strategies to deal with food insecurity in the acute
phase HIV infection included borrowing money (56.1%), followed by spousal
support, loans from microfinance institutions, banks, or money lenders, borrowing
food, or selling agricultural products. CONCLUSIONS: The present study revealed
that only about half of households with PLWHA were food secure. Prior
interventions relating to periods of food and economic crisis as well as
strategies for sustaining food security and economic status are needed in this
area.
PMID- 27499167
TI - Use of Protective Gloves in Nail Salons in Manhattan, New York City.
AB - OBJECTIVES: Nail salon owners in New York City (NYC) are required to provide
their workers with gloves and it is their responsibility to maintain healthy,
safe working spaces for their employees. The purpose of this study was to
determine the frequency with which nail salon workers wear protective gloves.
METHODS: A Freedom of Information Law request was submitted to New York
Department of State's Division of Licensing Services for a full list of nail
salons in Manhattan, NYC. A sample population of 800 nail salons was identified
and a simple random sample (without replacement) of 30% (n=240) was selected
using a random number generator. Researchers visited each nail salon from October
to December of 2015, posing as a potential customer to determine if nail salon
workers were wearing gloves. RESULTS: Among the 169 salons in which one or more
workers was observed providing services, a total of 562 workers were observed.
For 149 salons, in which one or more worker was observed providing services, none
of the workers were wearing gloves. In contrast, in six of the salons observed,
in which one or more workers was providing services, all of the workers (1 in 2
sites, 2 in 1 site, 3 in 2 sites, and 4 in 1 site) were wearing gloves. Almost
three-quarters of the total number of workers observed (n=415, 73.8%) were not
wearing gloves. CONCLUSIONS: The findings of this study indicate that, despite
recent media attention and legislation, the majority of nail salon workers we
observed were not wearing protective gloves when providing services.
PMID- 27499168
TI - A pivotal role of vacuolar H(+)-ATPase in regulation of lipid production in
Phaeodactylum tricornutum.
AB - Microalgal lipids have been considered as a promising source for biodiesel
production. Alkaline pH can induce neutral lipid accumulation in microalgae
cells. However, whether and how proton pumps, especially vacuolar H(+)-ATPase (V
ATPase), function in these processes is not well known. In this study, we treated
Phaeodactylum tricornutum with V-ATPase specific inhibitor bafilomycin A1 (BFA1)
to determine its role in lipid production. Firstly, V-ATPase activity was
increased in the latter phase of microalgae growth. BFA1 treatment decreased the
cell density and lipid contents. Further analysis showed that BFA1 treatment
reduced the number and size of oil bodies. GC-MS analysis showed that lipid
components were not affected by BFA1 treatment. Intracellular pH was decreased
and nitrogen depletion was delayed after BFA1 treatment. RNA-Seq analysis showed
that expression of genes involved in calcium signaling, sulfur metabolism, cell
cycle, glycolysis, pentose phosphate pathway, porphyrin, chlorophyll metabolism
and lipid catabolic metabolism were upregulated, while expression of genes
involved in ion transmembrane transport, ubiquitin mediated proteolysis, SNARE
interactions in vesicular transport, fatty acid biosynthesis were downregulated
under BFA1 treatment. Our findings provided insights into the molecular
mechanisms underlying lipid accumulation and the key genes involved in lipid
metabolism in Phaeodactylum tricornutum in response to BFA1.
PMID- 27499170
TI - An annulative transfer hydrogenation strategy enables straightforward access to
tetrahydro fused-pyrazine derivatives.
AB - A ruthenium-catalysed annulative transfer hydrogenation strategy, enabling
straightforward access to tetrahydro fused-pyrazine derivatives from N-heteroaryl
diamines and vicinal diols, has been demonstrated for the first time. Such a
synthesis proceeds with unprecedented synthetic effectiveness including high step
and atom efficiency, generation of water as the sole by-product, short reaction
time and no need for external high pressure H2 gas, offering an important basis
for the transformation of vicinal diols, a class of bio-mass derived resources,
into functionalized products.
PMID- 27499169
TI - Efficient shortcuts to adiabatic passage for three-dimensional entanglement
generation via transitionless quantum driving.
AB - We propose an effective scheme of shortcuts to adiabaticity for generating a
three-dimensional entanglement of two atoms trapped in a cavity using the
transitionless quantum driving (TQD) approach. The key point of this approach is
to construct an effective Hamiltonian that drives the dynamics of a system along
instantaneous eigenstates of a reference Hamiltonian to reproduce the same final
state as that of an adiabatic process within a much shorter time. In this paper,
the shortcuts to adiabatic passage are constructed by introducing two auxiliary
excited levels in each atom and applying extra cavity modes and classical fields
to drive the relevant transitions. Thereby, the three-dimensional entanglement is
obtained with a faster rate than that in the adiabatic passage. Moreover, the
influences of atomic spontaneous emission and photon loss on the fidelity are
discussed by numerical simulation. The results show that the speed of
entanglement implementation is greatly improved by the use of adiabatic shortcuts
and that this entanglement implementation is robust against decoherence. This
will be beneficial to the preparation of high-dimensional entanglement in
experiment and provides the necessary conditions for the application of high
dimensional entangled states in quantum information processing.
PMID- 27499171
TI - Valence-force model and nanomechanics of single-layer phosphorene.
AB - In order to understand the relation of strain and material properties, both a
microscopic model connecting a given strain to the displacement of atoms, and a
macroscopic model relating applied stress to induced strain, are required.
Starting from a valence-force model for black phosphorous [Kaneta et al., Solid
State Communications, 1982, 44, 613] we use recent experimental and computational
results to obtain an improved set of valence-force parameters for phosphorene.
From the model we calculate the phonon dispersion and the elastic properties of
single-layer phosphorene. Finally, we use these results to derive a complete
continuum model, including the bending rigidities, valid for long-wavelength
deformations of phosphorene. This continuum model is then used to study the
properties of pressurized suspended phosphorene sheets.
PMID- 27499173
TI - A technical application of quantitative next generation sequencing for chimerism
evaluation.
AB - At present, the most common genetic diagnostic method for chimerism evaluation
following hematopoietic stem cell transplantation is microsatellite analysis by
capillary electrophoresis. The main objective was to establish, through repeated
analysis over time, if a complete chimerism was present, or if the mixed
chimerism was stable, increasing or decreasing over time. Considering the recent
introduction of next generation sequencing (NGS) in clinical diagnostics, a
detailed study evaluating an NGS protocol was conducted, coupled with a custom
bioinformatics pipeline, for chimerism quantification. Based on the technology of
Ion AmpliSeq, a 44-amplicon custom chimerism panel was designed, and a custom
bioinformatics pipeline dedicated to the genotyping and quantification of NGS
data was coded. The custom chimerism panel allowed identification of an average
of 16 informative recipient alleles. The limit of detection of the protocol was
fixed at 1% due to the NGS background (<1%). The protocol followed the standard
Ion AmpliSeq library preparation and Ion Torrent Personal Genome Machine
guidelines. Overall, the present study added to the scientific literature,
identifying novel technical details for a possible future application of NGS for
chimerism quantification.
PMID- 27499174
TI - A Comparison of Single-Molecule Emission in Aluminum and Gold Zero-Mode
Waveguides.
AB - The effect of gold and aluminum zero-mode waveguides (ZMWs) on the brightness of
immobilized single emitters was characterized by probing fluorophores that absorb
in the green and red regions of the visible spectrum. Aluminum ZMWs enhance the
emission of Atto565 fluorophores upon green excitation, but they do not enhance
the emission of Atto647N fluorophores upon red excitation. Gold ZMWs increase
emission of both fluorophores with Atto647N showing enhancement that is threefold
higher than that observed for Atto565. This work indicates that 200 nm gold ZMWs
are better suited for single-molecule fluorescence studies in the red region of
the visible spectrum, while aluminum appears more suited for the green region of
the visible spectrum.
PMID- 27499175
TI - Accumulation of microcystins in a dominant Chironomid Larvae (Tanypus chinensis)
of a large, shallow and eutrophic Chinese lake, Lake Taihu.
AB - Although there have been numerous studies on microcystin (MC) accumulation in
aquatic organisms recently, the bioaccumulation of MCs in relatively small sized
organisms, as well as potential influencing factors, has been rarely studied.
Thus, in this study, we investigated the bioaccumulation of three MC congeners (
LR, -RR and -YR) in the chironomid larvae of Tanypus chinensis (an excellent food
source for certain fishes), the potential sources of these MCs, and potentially
relevant environmental parameters over the course of one year in Lake Taihu,
China. MC concentrations in T. chinensis varied temporally with highest
concentrations during the warmest months (except August 2013) and very low
concentrations during the remaining months. Among the three potential MC sources,
only intracellular MCs were significantly and positively correlated with MCs in
T. chinensis. Although MC concentrations in T. chinensis significantly correlated
with a series of physicochemical parameters of water column, cyanobacteria
species explained the most variability of MC accumulation, with the rest
primarily explained by extraMC-LR. These results indicated that ingestion of MC
producing algae of cyanobacteria accounted for most of the MC that accumulated in
T. chinensis. The high MC concentrations in T. chinensis may pose a potential
health threat to humans through trophic transfer.
PMID- 27499176
TI - Internal medicine network: Is it a newsworthy idea?
PMID- 27499172
TI - The molecular mechanisms of action of PPAR-gamma agonists in the treatment of
corneal alkali burns (Review).
AB - Corneal alkali burns (CAB) are characterized by injury-induced inflammation,
fibrosis and neovascularization (NV), and may lead to blindness. This review
evaluates the current knowledge of the molecular mechanisms responsible for CAB.
The processes of cytokine production, chemotaxis, inflammatory responses, immune
response, cell signal transduction, matrix metalloproteinase production and
vascular factors in CAB are discussed. Previous evidence indicates that
peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists suppress
immune responses, inflammation, corneal fibrosis and NV. This review also
discusses the role of PPAR-gamma as an anti-inflammatory, anti-fibrotic and anti
angiogenic agent in the treatment of CAB, as well as the potential role of PPAR
gamma in the pathological process of CAB. There have been numerous studies
evaluating the clinical profiles of CAB, and the aim of this systematic review
was to summarize the evidence regarding the treatment of CAB with PPAR-gamma
agonists.
PMID- 27499177
TI - Marijuana users do not have increased healthcare utilization: A National Health
and Nutrition Examination Survey (NHANES) study.
PMID- 27499178
TI - Long-term clinical outcome of elderly patients with acute coronary syndrome
treated with early percutaneous coronary intervention: Insights from the BASE ACS
randomized controlled trial: Bioactive versus everolimus-eluting stents in
elderly patients.
AB - BACKGROUND: The BASE ACS trial demonstrated an outcome of titanium-nitride-oxide
coated bioactive stents (BAS) that was non-inferior to everolimus-eluting stents
(EES) in patients presenting with acute coronary syndrome (ACS). We performed a
post hoc analysis of elderly versus non-elderly patients from the BASE ACS trial.
METHODS: We randomized 827 patients (1:1) presenting with ACS to receive either
BAS or EES. The primary endpoint was major adverse cardiac events (MACE): a
composite of cardiac death, non-fatal myocardial infarction (MI), or ischemia
driven target lesion revascularization (TLR). Follow-up was planned at 12months
and yearly thereafter for up to 7years. Elderly age was defined as >=65years.
RESULTS: Of the 827 patients enrolled in the BASE ACS trial, 360 (43.5%) were
elderly. Mean follow-up duration was 4.2+/-1.9years. MACE was more frequent in
elderly versus younger patients (19.7% versus 12.0%, respectively, p=0.002),
probably driven by more frequent cardiac death and non-fatal MI events (5.3%
versus 1.5%, and 9.7% versus 4.5%, p=0.002 and p=0.003, respectively). The rates
of ischemia-driven TLR were comparable (p>0.05). In propensity score-matched
analysis (215 pairs), only cardiac death was more frequent in elderly patients
(6% versus 1.4%, respectively, p=0.01). Diabetes independently predicted both
MACE and cardiac death in elderly patients. CONCLUSIONS: Elderly patients treated
with stent implantation for ACS had worse long-term clinical outcome, compared
with younger ones, mainly due to a higher death rate.
PMID- 27499179
TI - "From father to son": Early onset gout in Guidobaldo I da Montefeltro, Duke of
Urbino (1472-1508).
PMID- 27499180
TI - The Minimum Basic Data Set (MBDS) as a tool for cancer epidemiological
surveillance.
AB - OBJECTIVE: This work aims to evaluate the Minimum Basic Data Set (MBDS) as a data
source in the detection of malignant tumors and explore its usefulness as a tool
for epidemiological surveillance of cancer. MATERIALS AND METHODS: MBDS hospital
data discharge from Prince of Asturias University Hospital (HUPA, Alcala de
Henares, Madrid, Spain) and cancer cases recorded in the Hospital Cancer Registry
(HCR) have been collected for the period between January 2012 and June 2014. Both
databases have been linked by the number of clinical history. For the process of
evaluation of MBDS, the types of cancer with more than 100 cases have been
analyzed and sensitivity, specificity, positive and negative predictive
values(PPV, NPV) of MBDS were calculated using as reference the diagnoses
recorded in the HCR. RESULTS: 3438 cases of cancer were accounted in the MBDS and
2445 in the HCR. The MBDS has a sensitivity to detect cases of cancer above 60%,
although it varies depending on the type of tumor, reaching the highest values
for bladder cancer. The specificity and the VPN were very high for all types of
cancer studied, always on top of 95%. Finally, the VPP is generally moderate,
between 50% and 70%. CONCLUSIONS: The systematic exploitation of the MBDS can
provide a valuable tool in the monitoring of cancer by its acceptable sensitivity
and high specificity, allowing obtaining information without the delays involved
in the consolidation of the annotations of the HCR. Furthermore, its use could
partly mitigate the lack of data in important regions of Spain.
PMID- 27499181
TI - PTK7 overexpression in colorectal tumors: Clinicopathological correlation and
prognosis relevance.
AB - Colorectal cancer (CRC) has one of the highest mortality rates in the worldwide
and its incidence has been increasing in recent years. Protein tyrosine kinase-7
(PTK7) is an inactive member of receptor protein tyrosine kinase (RPTK)-like
molecules, which is involved in tumorigenesis of a variety of cancers. Our study
aimed to investigate expression of PTK7 in colorectal tumors (including benign
adenomas and malignant carcinomas), and its potential function in tumorigenesis
and prognosis. A total of 209 CRC patients and 28 colonic adenoma patients were
included in this study. Reverse transcription polymerase chain reaction (RT-PCR)
and quantitative real-time PCR were performed in 14 pairs of fresh frozen tissues
to evaluate mRNA expression of PTK7. Expression of PTK7 protein in 209 CRC
tissues with paired non-cancerous mucosa and 28 adenoma specimens were tested
using immunohistochemistry. The expression difference and its correlation with
clinicopathological features and overall survival were assessed by SPSS
statistics (version 22). P<0.05 was considered significant. RT-PCR and
quantitative real-time PCR showed a higher expression of PTK7 mRNA in CRC
compared with non-tumorous mucosa (4.87+/-3.71 vs. 1.33+/-1.05; P<0.001). PTK7
expression was significantly higher in adenoma (75%) and CRC (68.3%) than in non
tumorous mucosa (P<0.001). PTK7 expression was correlated with tumor
differentiation (P=0.027), lymph node metastasis (P=0.005), distant metastasis
(P=0.001) and TNM stage (P=0.028) of CRC patients. Significant correlation
between PTK7 overexpression and favorable overall survival of CRC patients was
observed (P=0.005). Therefore, it may act as a candidate biomarker to predict the
occurrence and prognosis of colorectal tumor.
PMID- 27499182
TI - Severe Babesia microti infection in an American immunocompetent patient diagnosed
in Spain.
AB - We report a severe Babesia microti infection in an immunocompetent patient
diagnosed in Spain. A 66-year-old woman coming from USA presented with fever,
thrombocytopenia, and multiorgan failure. Intraerythrocytic parasites were
observed in Giemsa-stained peripheral blood smears and B. microti was first
suspected by optical microscopy and afterward confirmed by specific polymerase
chain reaction (PCR). Patient received antibiotic therapy, vital support measures
and one red blood cell (RBC) exchange procedure. After 15 days, patient recovered
and she was transferred to her reference hospital. This case report highlights
the importance of clinical suspicion by physicians in non-endemic areas to
diagnose this entity, the differential diagnosis with malaria infection, and the
indication of RBC exchange as a therapeutic apheresis modality in the management
of severe forms.
PMID- 27499183
TI - Are prions transported by plasma exosomes?
AB - Blood has been shown to contain disease-associated misfolded prion protein
(PrP(TSE)) in animals naturally and experimentally infected with various
transmissible spongiform encephalopathy (TSE) agents, and in humans infected with
variant Creutzfeldt-Jakob disease (vCJD). Recently, we have demonstrated PrP(TSE)
in extracellular vesicle preparations (EVs) containing exosomes from plasma of
mice infected with mouse-adapted vCJD by Protein Misfolding Cyclic Amplification
(PMCA). Here we report the detection of PrP(TSE) by PMCA in EVs from plasma of
mice infected with Fukuoka-1 (FU), an isolate from a Gerstmann-Straussler
Scheinker disease patient. We used Tga20 transgenic mice that over-express mouse
cellular prion protein, to assay by intracranial injections the level of
infectivity in a FU-infected brain homogenate from wild-type mice (FU-BH), and in
blood cellular components (BCC), consisting of red blood cells, white blood cells
and platelets, plasma EVs, and plasma EVs subjected to multiple rounds of PMCA.
Only FU-BH and plasma EVs from FU-infected mice subjected to PMCA that contained
PrP(TSE) transmitted disease to Tga20 mice. Plasma EVs not subjected to PMCA and
BCC from FU-infected mice failed to transmit disease. These findings confirm the
high sensitivity of PMCA for PrP(TSE) detection in plasma EVs and the efficiency
of this in vitro method to produce highly infectious prions. The results of our
study encourage further research to define the role of EVs and, more specifically
exosomes, as blood-borne carriers of PrP(TSE).
PMID- 27499184
TI - Competing Orders and Anomalies.
AB - A conservation law is one of the most fundamental properties in nature, but a
certain class of conservation "laws" could be spoiled by intrinsic quantum
mechanical effects, so-called quantum anomalies. Profound properties of the
anomalies have deepened our understanding in quantum many body systems. Here, we
investigate quantum anomaly effects in quantum phase transitions between
competing orders and striking consequences of their presence. We explicitly
calculate topological nature of anomalies of non-linear sigma models (NLSMs) with
the Wess-Zumino-Witten (WZW) terms. The non-perturbative nature is directly
related with the 't Hooft anomaly matching condition: anomalies are conserved in
renormalization group flow. By applying the matching condition, we show massless
excitations are enforced by the anomalies in a whole phase diagram in sharp
contrast to the case of the Landau-Ginzburg-Wilson theory which only has massive
excitations in symmetric phases. Furthermore, we find non-perturbative criteria
to characterize quantum phase transitions between competing orders. For example,
in 4D, we show the two competing order parameter theories, CP(1) and the NLSM
with WZW, describe different universality class. Physical realizations and
experimental implication of the anomalies are also discussed.
PMID- 27499185
TI - Serological evidence of infection with rodent-borne hepatitis E virus HEV-C1 or
antigenically related virus in humans.
AB - Zoonotic potential of a rat-derived hepatitis E virus (HEV), designated as HEV
C1, remains unknown. To evaluate the risk for HEV-C1 infection in humans, paired
sera of 208 hospitalized febrile patients collected from 2001 to 2003 in Hanoi,
Vietnam, were examined for IgG antibodies to HEV-C1 and genotype 1 HEV (HEV-1),
which is common in humans. IgG antibodies to virus-like particles (VLPs) of HEV
C1 and/or HEV-1 were detected from 99 of the 208 convalescent sera in enzyme
linked immunosorbent assay (ELISA). IgG antibody titers to HEV-C1 antigen in 3 of
the 99 sera were more than 8-fold higher than those to HEV-1 antigen. IgM
antibodies to HEV-C1 antigen were detected in acute sera from 2 of the 3 patients
in ELISA and Western blotting. However, no HEV genome was detected. Clinical
information was available for 1 of the 2 patients. Hepatic enzymes, aspartate
aminotransferase and alanine aminotransferase, were mildly elevated (156 IU/l and
68 IU/l, respectively), and hepatomegaly was detected by ultrasonography. The
patient recovered from the illness after 17 days. These results indicated that
HEV-C1 or its variants infect humans in Vietnam and may cause acute febrile
illness with mild liver dysfunction.
PMID- 27499186
TI - Marked Sexual Dimorphism in the Role of the Ryanodine Receptor in a Model of Pain
Chronification in the Rat.
AB - Hyperalgesic priming, an estrogen dependent model of the transition to chronic
pain, produced by agonists at receptors that activate protein kinase C epsilon
(PKCepsilon), occurs in male but not in female rats. However, activation of
second messengers downstream of PKCepsilon, such as the ryanodine receptor,
induces priming in both sexes. Since estrogen regulates intracellular calcium, we
investigated the interaction between estrogen and ryanodine in the susceptibility
to develop priming in females. The lowest dose of ryanodine able to induce
priming in females (1 pg) is 1/100,000(th) that needed in males (100 ng), an
effect dependent on the activation of ryanodine receptors. Treatment of female
rats with antisense to estrogen receptor alpha (ERalpha), but not beta (ERbeta),
mRNA, prevented the induction of priming by low dose ryanodine, and the ERalpha
agonist, PPT, induced ryanodine receptor-dependent priming. In vitro application
of ryanodine in low concentration (2 nM) to small DRG neurons cultured from
females, significantly potentiated calcium release via ryanodine receptors
induced by caffeine. This effect was only observed in IB4+ neurons, cultured in
the presence of beta-estradiol or PPT. Our results demonstrate a profound
regulatory role of ERalpha in ryanodine receptor-dependent transition to chronic
pain.
PMID- 27499187
TI - Clustering of adherence to personalised dietary recommendations and changes in
healthy eating index within the Food4Me study.
AB - OBJECTIVE: To characterise clusters of individuals based on adherence to dietary
recommendations and to determine whether changes in Healthy Eating Index (HEI)
scores in response to a personalised nutrition (PN) intervention varied between
clusters. DESIGN: Food4Me study participants were clustered according to whether
their baseline dietary intakes met European dietary recommendations. Changes in
HEI scores between baseline and month 6 were compared between clusters and
stratified by whether individuals received generalised or PN advice. SETTING: Pan
European, Internet-based, 6-month randomised controlled trial. SUBJECTS: Adults
aged 18-79 years (n 1480). RESULTS: Individuals in cluster 1 (C1) met all
recommended intakes except for red meat, those in cluster 2 (C2) met two
recommendations, and those in cluster 3 (C3) and cluster 4 (C4) met one
recommendation each. C1 had higher intakes of white fish, beans and lentils and
low-fat dairy products and lower percentage energy intake from SFA (P<0.05). C2
consumed less chips and pizza and fried foods than C3 and C4 (P<0.05). C1 were
lighter, had lower BMI and waist circumference than C3 and were more physically
active than C4 (P<0.05). More individuals in C4 were smokers and wanted to lose
weight than in C1 (P<0.05). Individuals who received PN advice in C4 reported
greater improvements in HEI compared with C3 and C1 (P<0.05). CONCLUSIONS: The
cluster where the fewest recommendations were met (C4) reported greater
improvements in HEI following a 6-month trial of PN whereas there was no
difference between clusters for those randomised to the Control, non-personalised
dietary intervention.
PMID- 27499188
TI - Human behaviors elevating the risk of exposure to Ixodes ricinus larvae and
nymphs in two types of lowland coniferous forests in west-central Poland.
AB - Ixodes ricinus L. is the commonest tick encountered by humans in Central Europe
and the most important vector of tick-borne diseases (TBD) in Europe. Foresters
represent a group at elevated risk of exposure to I. ricinus throughout Europe.
Here, we employed an experimental design similar to one used previously to
determine what behavioral factors heighten exposure to questing Ixodes pacificus
nymphs in a hardwood forest in the far-western United States. Five activities
were evaluated systematically in a coniferous forest and a mixed broadleaved
forest in west-central Poland: (i) walking in low-cut running shoes; (ii) sitting
atop logs; (iii) sitting on leaf litter; (iv) sitting against tree trunks; and
(v) gathering firewood. In total, 540 I. ricinus ticks were collected (198
larvae, 327 nymphs, 15 adults) in spring and late summer. Many more ticks were
collected in spring than in late summer, and in the mixed broadleaved forest
versus the coniferous forest. The riskiest behavior for acquiring nymphs in both
spring and late summer was gathering firewood, though sitting atop logs was
nearly as perilous in late summer. In contrast, the riskiest behaviors for
encountering larvae in spring and late summer were sitting against trunks and
sitting on leaf litter, respectively. Pairwise comparisons revealed only two
significant associations among the variables explored for the nymphs: season and
human gender, and season and type of forest. For larval ticks, the most
significant associations were gender and sitting behaviors and for type of forest
and sitting on leaf litter or against tree trunks. The most commonly infested
body region was the lower legs.
PMID- 27499189
TI - Physiological Proteins in Therapeutics: A Current Review on Interferons.
AB - Interferons are produced in vivo and are one of the prime components of natural
defense system of animals. They are released by the viral infected cells and
provide protection to the neighboring cells against viral infection. The cyto
protective property of the proteins ignited the thought of their pharmaceutical
adaptation for therapeutic use against viral diseases in individuals in whom the
interferons released naturally are not sufficient to combat the situation.
Interferon supplements have been found to complement various antiviral drugs.
Considering the efficacy of interferons in regulating angiogenesis and
immunomodulation, they can be adapted for therapy of the killer diseases like
cancer and AIDS. We have come ahead more than twenty five years after the
approval of clinical use of interferon as drugs and are today really in a
position to promise a disease free life to our present and next generation.
Interferon therapy will be contributing a big share to the upcoming remedies for
the new diseases and we are thus armed to fight back the deadly viral threats.
Interferons have been modified [pegylated etc.] and have already been adapted to
some extent in certain diseases and are in regular use in some. Thus interferons
if modified as per need and used in combination with either antiviral drugs,
antibiotics, antioxidants may strengthen our defense system effectively to bring
about a strong protection against wide range of diseases.
PMID- 27499190
TI - Glycosylation and Activities of Natural Products.
AB - Natural products are widely found in nature, their number and variety are
numerous, the structures are complex and diverse. These natural products have
many physiological and pharmacological activities. Glycosylation can increase the
diversity of structure and function of natural product, it has become the focus
of drug research and development. The impacts of glycosylation of natural
products to water solubility, pharmacological activities, bioavailability, or
others were described in this review, which provides a reference for the
development and application of glycosylated natural products.
PMID- 27499191
TI - Prospective observational study on central line-associated bloodstream infections
and central venous catheter occlusions using a negative displacement connector
with an alcohol disinfecting cap.
AB - BACKGROUND: Major complications of central venous catheter (CVC) use include
bloodstream infection and occlusion. We performed a prospective, observational
study to determine the rate of central line-associated bloodstream infection
(CLABSI) and CVC occlusion using a negative displacement connector with an
alcohol disinfecting cap. METHODS: Patients were followed from the time of CVC
insertion through 2 days after removal, at the time of hospital discharge if
there was no documentation of removal, or 90 days after the insertion of the CVC
if it was not removed. CLABSI was defined using National Healthcare Safety
Network criteria. Data for evidence of lumen occlusions were extracted from the
electronic health record. Direct observations were performed to assess adherence
to hospital policy regarding CVC insertion practice. RESULTS: A total of 2,512
catheters from 2,264 patients were enrolled for this study. There were 21 CLABSIs
(0.84%; 95% confidence interval [CI], 0.48%-1.19%; 0.62 per 1,000 line days) and
378 occlusions (15.05%; 95% CI, 13.65%-16.45%; 11.23 per 1,000 line days). Eighty
five direct observations demonstrated insertion protocol adherence in 881 of 925
(95.24%; 95% CI, 93.87%-96.61%) measured criteria. CONCLUSIONS: Lines placed
following a standardized protocol using a negative displacement connector with an
alcohol cap have low rates of infection compared with historically published
findings. We also established that the occlusion rate is >15-fold the CLABSI
rate.
PMID- 27499192
TI - Association between chronic hemodialysis and bloodstream infections caused by
chromosomally mediated AmpC-producing Enterobacteriaceae.
AB - BACKGROUND: The combination of inherent antimicrobial resistance and high
mortality after bloodstream infections (BSIs) caused by chromosomally mediated
AmpC-producing Enterobacteriaceae (CAE) emphasizes the importance of identifying
patients at risk of BSI because of these bacteria. This retrospective case
control study examines chronic hemodialysis among other risk factors for BSI
caused by CAE. METHODS: Hospitalized adults with Enterobacteriaceae BSI from
January 1, 2010-June 30, 2014, at 2 large community hospitals in the Southeastern
United States were identified. Multivariate logistic regression was used to
examine risk factors for CAE BSI. RESULTS: Among 831 Enterobacteriaceae
bloodstream isolates, 106 (13%) met the phenotypic definition of CAE.
Enterobacter spp accounted for 47% (50/106) of CAE BSIs. Chronic hemodialysis was
an independent risk factor for CAE BSI (adjusted odds ratio [aOR], 2.34; 95%
confidence interval [CI], 1.21-4.44). Other predictors of CAE BSI included
nosocomial acquisition (aOR, 1.72; 95% CI, 1.02-2.87) and exposure to beta-lactam
antibiotics within the last 30 days (aOR, 2.39; 95% CI, 1.37-4.14). CONCLUSIONS:
To our knowledge, this is the first study to demonstrate an increased risk of CAE
BSI in patients with end-stage renal disease undergoing chronic hemodialysis.
This highlights the importance of effective infection prevention and
antimicrobial stewardship interventions in hemodialysis clinics. Further studies
to examine the impact of antibiotics on intestinal microbiota and rates of CAE
colonization in this patient population are warranted.
PMID- 27499193
TI - Ebola: Emergency preparedness and perceived response of Malaysian health care
providers.
AB - We studied the emergency preparedness and perceived response for Ebola virus
disease among various health care providers in Malaysia using a self-report
questionnaire. Most of the health care providers felt that they were able to
respond to Ebola virus disease and were aware of the level of preparedness needed
during emergency.
PMID- 27499194
TI - Knowledge, source of information, and perception of Portuguese medical students
and junior doctors of infection control precautions.
AB - Medical education should include infection control precautions (ICPs). Portuguese
medical students showed reasonable knowledge in ICPs; however, contact isolation
and glove and mask use should be reinforced. Only 25% referred to the curriculum
as the most important information source. There was a positive association
between academic year (P = .032), previous training in ICPs (P = .016), and
knowledge. Main strategies proposed to acquire competences in ICPs were bedside
teaching (26.9%) and curriculum and bedside teaching (20.2%).
PMID- 27499195
TI - Control of an outbreak of postoperative bone mucormycosis: An intervention study
of contiguous cohorts.
AB - An outbreak of postoperative bone mucormycosis following arthroscopic anterior
cruciate ligament reconstruction in a tertiary referral center in Parana,
Argentina, could have been transmitted through an arthroscopic anterior cruciate
ligament reconstruction-exclusive contaminated item. The outbreak was controlled
after changing from a system of direct delivery of implants and instruments to
the operating room without proper verification, to a controlled and centralized
process; specifically, the institution's pharmacy verified the quality and
traceability of implants, and instruments were processed only by the
institution's central sterile services department.
PMID- 27499196
TI - Isolation and evaluation of proteolytic actinomycete isolates as novel inducers
of pearl millet downy mildew disease protection.
AB - Native endophytic actinomycetes isolated from pearl millet roots were examined
for their efficacy to protect pearl millet against downy mildew. Nineteen of 39
isolates were found to be proteolytic, of which 7 strains could directly suppress
the sporangium formation of Sclerospora graminicola, the pearl millet downy
mildew pathogen. Thus, mycelial suspensions containing either spores or cell-free
extract of these 7 isolates were used for seed-coating and -soaking treatments to
test for their induction of downy mildew resistance. Results indicated that seed
coating overall provided better protection to downy mildew than seed-soaking. In
both treatments, the tested isolates demonstrated differential abilities in downy
mildew disease protection, with Streptomyces griseus SJ_UOM-07-09 and
Streptosporangium roseum SJ_UOM-18-09 showing the highest protection rates.
Additionally, the levels of disease protection conferred by the actinomycetes
were just slightly lower than that of the systemic fungicide Apron, suggesting
their effectiveness. Further studies revealed that the more rapid root
colonization by SJ_UOM-18-09 resulted in faster and higher induced resistance in
comparison with SJ_UOM-07-09 under greenhouse conditions, indicating that SJ_UOM
18-09 was superior than SJ_UOM-07-09 in inducing resistance. Results from this
study provide comprehensive information on biocontrol functions of SJ_UOM- 18-09
with great potential to control downy mildew disease in pearl millet.
PMID- 27499197
TI - Legal protection of the right to work and employment for persons with mental
health problems: a review of legislation across the world.
AB - The right to work and employment is indispensable for social integration of
persons with mental health problems. This study examined whether existing laws
pose structural barriers in the realization of right to work and employment of
persons with mental health problems across the world. It reviewed disability
specific, human rights legislation, and labour laws of all UN Member States in
the context of Article 27 of the UN Convention on the Rights of Persons with
Disabilities (CRPD). It wes found that laws in 62% of countries explicitly
mention mental disability/impairment/illness in the definition of disability. In
64% of countries, laws prohibit discrimination against persons with mental health
during recruitment; in one-third of countries laws prohibit discontinuation of
employment. More than half (56%) the countries have laws in place which offer
access to reasonable accommodation in the workplace. In 59% of countries laws
promote employment of persons with mental health problems through different
affirmative actions. Nearly 50 years after the adoption of the International
Covenant on Economic, Social, and Cultural Rights and 10 years after the adoption
of CRPD by the UN General Assembly, legal discrimination against persons with
mental health problems continues to exist globally. Countries and policy-makers
need to implement legislative measures to ensure non-discrimination of persons
with mental health problems during employment.
PMID- 27499198
TI - Dynamics of ionic liquids in bulk and in confinement by means of (1)H NMR
relaxometry - BMIM-OcSO4 in an SiO2 matrix as an example.
AB - (1)H nuclear magnetic resonance relaxometry is applied to reveal information on
the translational and rotational dynamics of the ionic liquid: 1-butyl-3-methyl
imidazoliumoctyl sulfate (BMIM-OcSO4) in bulk and in a confinement formed by a
nanoporous SiO2 matrix. The experimental studies were performed in a very broad
frequency range, from 8 kHz to 40 MHz (referring to the (1)H resonance
frequency), in order to probe motional processes at very different time scales
using a single experiment, and in the temperature range of 243-303 K. The
relaxation results for BMIM-OcSO4 in bulk are interpreted in terms of three
relaxation contributions: a term associated with the translational dynamics of
the ions (it has been assumed that the translational dynamics of cations and
anions can be described by one diffusion coefficient) and two terms associated
with the rotational motion of the anion and the cation, respectively. The
relationships between the obtained dynamic parameters (rotational correlation
times and translational diffusion coefficients) are thoroughly discussed and used
as a "reference" for the dynamics of BMIM-OcSO4 confined in an SiO2 matrix.
Analysis of the corresponding relaxation data for the confined liquid shows that
the confinement does not significantly affect the rotational dynamics, but it has
a considerable impact on the translational motion. It is demonstrated that the
relaxation term associated with the translational dynamics stems from two
contributions: a contribution from a core (bulk-like) fraction of the liquid and
from a fraction moving near the pore surface and therefore being for some time
adsorbed on the pore walls. The translational diffusion coefficient for the last
fraction is determined and several conclusions regarding the residence lifetime
of the ions on the surface are drawn. Moreover, an additional motional process on
the timescale of ns or shorter is revealed in the confinement.
PMID- 27499199
TI - Haemopedia: An Expression Atlas of Murine Hematopoietic Cells.
AB - Hematopoiesis is a multistage process involving the differentiation of stem and
progenitor cells into distinct mature cell lineages. Here we present Haemopedia,
an atlas of murine gene-expression data containing 54 hematopoietic cell types,
covering all the mature lineages in hematopoiesis. We include rare cell
populations such as eosinophils, mast cells, basophils, and megakaryocytes, and a
broad collection of progenitor and stem cells. We show that lineage branching and
maturation during hematopoiesis can be reconstructed using the expression
patterns of small sets of genes. We also have identified genes with enriched
expression in each of the mature blood cell lineages, many of which show
conserved lineage-enriched expression in human hematopoiesis. We have created an
online web portal called Haemosphere to make analyses of Haemopedia and other
blood cell transcriptional datasets easier. This resource provides simple tools
to interrogate gene-expression-based relationships between hematopoietic cell
types and genes of interest.
PMID- 27499200
TI - Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an
Immunodeficient Mouse Model with Kit(Wv) Mutations.
AB - In human-to-mouse xenograft models, reconstitution of human hematopoiesis is
usually B-lymphoid dominant. Here we show that the introduction of homozygous
Kit(Wv) mutations into C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS)
strongly promoted human multi-lineage reconstitution. After xenotransplantation
of human CD34(+)CD38(-) cord blood cells, these newly generated
C57BL/6.Rag2(null)Il2rg(null)NOD-Sirpa Kit(Wv/Wv) (BRGSK(Wv/Wv)) mice showed
significantly higher levels of human cell chimerism and long-term multi-lineage
reconstitution compared with BRGS mice. Strikingly, this mouse displayed a robust
reconstitution of human erythropoiesis and thrombopoiesis with terminal
maturation in the bone marrow. Furthermore, depletion of host macrophages by
clodronate administration resulted in the presence of human erythrocytes and
platelets in the circulation. Thus, attenuation of mouse KIT signaling greatly
enhances the multi-lineage differentiation of human hematopoietic stem and
progenitor cells (HSPCs) in mouse bone marrow, presumably by outcompeting mouse
HSPCs to occupy suitable microenvironments. The BRGSK(Wv/Wv) mouse model is a
useful tool to study human multi-lineage hematopoiesis.
PMID- 27499201
TI - A Cas9 Variant for Efficient Generation of Indel-Free Knockin or Gene-Corrected
Human Pluripotent Stem Cells.
AB - While Cas9 nucleases permit rapid and efficient generation of gene-edited cell
lines, the CRISPR-Cas9 system can introduce undesirable "on-target" mutations
within the second allele of successfully modified cells via non-homologous end
joining (NHEJ). To address this, we fused the Streptococcus pyogenes Cas9
(SpCas9) nuclease to a peptide derived from the human Geminin protein (SpCas9
Gem) to facilitate its degradation during the G1 phase of the cell cycle, when
DNA repair by NHEJ predominates. We also use mRNA transfection to facilitate low
and transient expression of modified and unmodified versions of Cas9. Although
the frequency of homologous recombination was similar for SpCas9-Gem and SpCas9,
we observed a marked reduction in the capacity for SpCas9-Gem to induce NHEJ
mediated indels at the target locus. Moreover, in contrast to native SpCas9, we
demonstrate that transient SpCas9-Gem expression enables reliable generation of
both knockin reporter cell lines and genetically repaired patient-specific
induced pluripotent stem cell lines free of unwanted mutations at the targeted
locus.
PMID- 27499203
TI - Applications of N-heterocyclic imines in main group chemistry.
AB - The imidazolin-2-imino group is an N-heterocyclic imino functionality that
derives from the class of compounds known as guanidines. The exocyclic nitrogen
atom preferably bonds to electrophiles and its electron-donating character is
markedly enhanced by efficient delocalization of cationic charge density into the
five-membered imidazoline ring. Thus, this imino group is an excellent choice for
thermodynamic stabilization of electron-deficient species. Due to the variety of
available imidazoline-based precursors to this ligand, its steric demand can be
tailored to meet the requirements for kinetic stabilization of otherwise highly
reactive species. Consequently, it does not come as a surprise that the
imidazolin-2-iminato ligand has found widespread applications in transition-metal
chemistry to furnish pincer complexes or "pogo stick" type compounds. In
comparison, the field of main-group metal compounds of this ligand is still in
its infancy; however, it has received growing attention in recent years. A
considerable number of electron-poor main-group element species have been
described today which are stabilized by N-heterocyclic iminato ligands. These
include low-valent metal cations and species that are marked by formerly unknown
bonding modes. In this article we provide an overview on the present chemistry of
main-group element compounds of the imidazolin-2-iminato ligand, as well as
selected examples for the related imidazolidin- and benzimidazolin-2-imino
system.
PMID- 27499202
TI - Constraints on the Radical Cation Center of Cytochrome c Peroxidase for Electron
Transfer from Cytochrome c.
AB - The tryptophan 191 cation radical of cytochrome c peroxidase (CcP) compound I
(Cpd I) mediates long-range electron transfer (ET) to cytochrome c (Cc). Here we
test the effects of chemical substitution at position 191. CcP W191Y forms a
stable tyrosyl radical upon reaction with peroxide and produces spectral
properties similar to those of Cpd I but has low reactivity toward reduced Cc.
CcP W191G and W191F variants also have low activity, as do redox ligands that
bind within the W191G cavity. Crystal structures of complexes between Cc and CcP
W191X (X = Y, F, or G), as well as W191G with four bound ligands reveal similar
1:1 association modes and heme pocket conformations. The ligands display
structural disorder in the pocket and do not hydrogen bond to Asp235, as does
Trp191. Well-ordered Tyr191 directs its hydroxyl group toward the porphyrin ring,
with no basic residue in the range of interaction. CcP W191X (X = Y, F, or G)
variants substituted with zinc-porphyrin (ZnP) undergo photoinduced ET with
Cc(III). Their slow charge recombination kinetics that result from loss of the
radical center allow resolution of difference spectra for the charge-separated
state [ZnP(+), Cc(II)]. The change from a phenyl moiety at position 191 in W191F
to a water-filled cavity in W191G produces effects on ET rates much weaker than
the effects of the change from Trp to Phe. Low net reactivity of W191Y toward
Cc(II) derives either from the inability of ZnP(+) or the Fe-CcP ferryl to
oxidize Tyr or from the low potential of the resulting neutral Tyr radical.
PMID- 27499205
TI - Cash dieting-calories per dollar: A novel approach to inform food choices?
PMID- 27499204
TI - Beta rhythm modulation by speech sounds: somatotopic mapping in somatosensory
cortex.
AB - During speech listening motor regions are somatotopically activated, resembling
the activity that subtends actual speech production, suggesting that motor
commands can be retrieved from sensory inputs. Crucially, the efficient motor
control of the articulators relies on the accurate anticipation of the
somatosensory reafference. Nevertheless, evidence about somatosensory activities
elicited by auditory speech processing is sparse. The present work looked for
specific interactions between auditory speech presentation and somatosensory
cortical information processing. We used an auditory speech identification task
with sounds having different place of articulation (bilabials and dentals). We
tested whether coupling the auditory task with a peripheral electrical
stimulation of the lips would affect the pattern of sensorimotor
electroencephalographic rhythms. Peripheral electrical stimulation elicits a
series of spectral perturbations of which the beta rebound reflects the return-to
baseline stage of somatosensory processing. We show a left-lateralized and
selective reduction in the beta rebound following lip somatosensory stimulation
when listening to speech sounds produced with the lips (i.e. bilabials). Thus,
the somatosensory processing could not return to baseline due to the recruitment
of the same neural resources by speech stimuli. Our results are a clear
demonstration that heard speech sounds are somatotopically mapped onto
somatosensory cortices, according to place of articulation.
PMID- 27499206
TI - Predictors of dietary diversity in children ages 6 to 23 mo in largely food
insecure area of South Wollo, Ethiopia.
AB - OBJECTIVE: The aim of this study was to assess the level and predictors of
dietary diversity (DD) in predominantly food-insecure area of South Wollo,
Ethiopia among children ages 6 to 23 mo. METHODS: The study was conducted in
October 2014. We selected 2080 children using a multistage sampling technique. DD
in the preceding day of the survey was assessed with the standard seven-food
group score. Predictors of DD were identified via Poisson regression model and
the outputs are presented using adjusted incidence rate ratio (IRR) with 95%
confidence interval (CI). RESULTS: Only 7% (95% CI, 5.9%-8.1%) of the children
met the recommended minimum DD. Child age and maternal knowledge of infant and
young child feeding (IYCF) were significant predictors of DD with IRR of 1.027
(95% CI, 1.022-1.032) and 1.026 (95% CI, 1.010-1.043). Households with moderate
and severe food insecurity had 9% (95% CI, 3.8-13.9%) and 24.9% (95% CI, 14.6
44%) reduced chance of providing diversified food. Husbands' direct involvement
in IYCF increased DD by 13.7% (95% CI, 7.4-20.4). Caregivers who discussed IYCF
with health extension workers, participated in cooking demonstrations, and heard
radio spots about IYCF in the preceding 3 mo had 11.7% (95% CI, 3.4-20.7%), 18.9%
(95% CI, 0.3-40.9%), and 11.4% (95% CI, 4.8-18.4) higher chance of providing
diversified food, respectively. Backyard gardening (IRR, 1.088; 95% CI, 1.031
1.148) and number of chickens owned (IRR, 1.011; 95% CI, 1.001-1.021) also were
significant predictors. CONCLUSIONS: In predominately food-insecure areas,
nutrition education, implementation of nutrition-sensitive agriculture, and
husband involvement in IYCF can improve children's DD.
PMID- 27499207
TI - Vascular toxicity of silver nanoparticles to developing zebrafish (Danio rerio).
AB - Nanoparticles (NPs, 1-100 nm) can enter the environment and result in exposure to
humans and other organisms leading to potential adverse health effects. The aim
of the present study is to evaluate the effects of early life exposure to
polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs, 50 nm), particularly
with respect to vascular toxicity on zebrafish embryos and larvae (Danio rerio).
Previously published data has suggested that PVP-AgNP exposure can inhibit the
expression of genes within the vascular endothelial growth factor (VEGF)
signaling pathway, leading to delayed and abnormal vascular development. Here, we
show that early acute exposure (0-12 h post-fertilization, hpf) of embryos to PVP
AgNPs at 1 mg/L or higher results in a transient, dose-dependent induction in
VEGF-related gene expression that returns to baseline levels at hatching (72
hpf). Hatching results in normoxia, negating the effects of AgNPs on vascular
development. Interestingly, increased gene transcription was not followed by the
production of associated proteins within the VEGF pathway, which we attribute to
NP-induced stress in the endoplasmic reticulum (ER). The impaired translation may
be responsible for the observed delays in vascular development at later stages,
and for smaller larvae size at hatching. Silver ion (Ag(+)) concentrations were <
0.001 mg/L at all times, with no significant effects on the VEGF pathway. We
propose that PVP-AgNPs temporarily delay embryonic vascular development by
interfering with oxygen diffusion into the egg, leading to hypoxic conditions and
ER stress.
PMID- 27499208
TI - Iron depletion-induced downregulation of N-cadherin expression inhibits invasive
malignant phenotypes in human esophageal cancer.
AB - Esophageal carcinomas often have a poor prognosis due to early lymph node
metastasis. Epithelial-mesenchymal transition (EMT) is strongly associated with
the acquisition of cancer metastasis and invasion. However, there is no
established treatment to eliminate the EMT of cancer cells. Iron is an essential
element for both normal and cancer cells in humans. Recently, iron depletion has
been discovered to suppress tumor growth. Therefore, we hypothesized that
decreased iron conditions would regulate EMT phenotypes, as well as suppressing
tumor growth. The human TE esophageal cancer cell lines and OE19 were used in our
study. Decreased iron conditions were made using an iron-depletion diet in mice
and the iron chelator deferasirox for cell studies. Migration and invasion
abilities of cells were measured using migration, invasion, and sphere-formation
assays. Esophageal subcutaneous tumor growth was suppressed in decreased iron
conditions. In vitro study showed that decreased iron conditions inhibited
esophageal cancer cell proliferation as well as migration and invasion abilities,
with downregulation of N-cadherin expression. Also, migration and invasion
abilities were suppressed by inhibiting expression of N-cadherin. In conclusion,
decreased iron conditions revealed a profound anticancer effect by the
suppression of tumor growth and the inhibition of migration and invasion
abilities via N-cadherin.
PMID- 27499210
TI - Role of the pectoralis major myofascial flap in preventing pharyngocutaneous
fistula following salvage laryngectomy.
AB - OBJECTIVE: This study aimed to assess the utility of onlay pectoralis major
myofascial flap in preventing pharyngocutaneous fistula following salvage total
laryngectomy. METHODS: A retrospective analysis was performed of 172 patients who
underwent salvage laryngectomy for recurrent carcinoma of the larynx or
hypopharynx between 1999 and 2014. One hundred and ten patients underwent primary
closure and 62 patients had pectoralis major myofascial flap onlay. RESULTS: The
overall pharyngocutaneous fistula rate was 43 per cent, and was similar in both
groups (primary closure group, 43.6 per cent; onlay flap group, 41.9 per cent; p
= 0.8). Fistulae in the onlay flap group healed faster: the median and mean
fistula duration were 37 and 55 days, respectively, in the primary closure group
and 20 and 25 days, respectively, in the onlay flap group (p = 0.008).
CONCLUSION: Use of an onlay pectoralis major myofascial flap did not decrease the
pharyngocutaneous fistula rate, although fistula duration was shortened. A well
designed randomised-controlled trial is needed to establish parameters for its
routine use in clinical practice.
PMID- 27499209
TI - Dynamic contrast-enhanced MRI detects acute radiotherapy-induced alterations in
mandibular microvasculature: prospective assessment of imaging biomarkers of
normal tissue injury.
AB - Normal tissue toxicity is an important consideration in the continued development
of more effective external beam radiotherapy (EBRT) regimens for head and neck
tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity
represents a crucial step in decreasing potential toxicity. To date, no imaging
modality has been shown to detect changes in bone vascularity in real time during
treatment. Based on our institutional experience with multi-parametric MRI, we
hypothesized that DCE-MRI can provide in-treatment information regarding EBRT
induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT
treatment for head and neck cancer were prospectively imaged prior to, mid
course, and following treatment. DCE-MRI scans were co-registered to dosimetric
maps to correlate EBRT dose and change in mandibular bone vascularity as measured
by Ktrans and Ve. DCE-MRI was able to detect dose-dependent changes in both
Ktrans and Ve in a subset of patients. One patient who developed ORN during the
study period demonstrated decreases in Ktrans and Ve following treatment
completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can
detect dose-dependent alterations in mandibular bone vascularity during
chemoradiotherapy, providing biomarkers that are physiological correlates of
acute of acute mandibular vascular injury and recovery temporal kinetics.
PMID- 27499211
TI - Comparative Assessment of Models and Methods To Calculate Grid Electricity
Emissions.
AB - Due to the complexity of power systems, tracking emissions attributable to a
specific electrical load is a daunting challenge but essential for many
environmental impact studies. Currently, no consensus exists on appropriate
methods for quantifying emissions from particular electricity loads. This paper
reviews a wide range of the existing methods, detailing their functionality,
tractability, and appropriate use. We identified and reviewed 32 methods and
models and classified them into two distinct categories: empirical data and
relationship models and power system optimization models. To illustrate the
impact of method selection, we calculate the CO2 combustion emissions factors
associated with electric-vehicle charging using 10 methods at nine charging
station locations around the United States. Across the methods, we found an up to
68% difference from the mean CO2 emissions factor for a given charging site among
both marginal and average emissions factors and up to a 63% difference from the
average across average emissions factors. Our results underscore the importance
of method selection and the need for a consensus on approaches appropriate for
particular loads and research questions being addressed in order to achieve
results that are more consistent across studies and allow for soundly supported
policy decisions. The paper addresses this issue by offering a set of
recommendations for determining an appropriate model type on the basis of the
load characteristics and study objectives.
PMID- 27499212
TI - Leishmania exosomes and other virulence factors: Impact on innate immune response
and macrophage functions.
AB - Leishmania parasites are the causative agents of the leishmaniases, a collection
of vector-borne diseases that range from simple cutaneous to fatal visceral
forms. Employing potent immune modulation mechanisms, Leishmania is able to
render the host macrophage inactive and persist inside its phagolysosome. In the
last few years, the role of exosomes in Leishmania-host interactions has been
increasingly investigated. For instance, it was reported that Leishmania exosome
release is augmented following temperature shift, a condition mimicking
parasite's entry into its mammalian host. Leishmania exosomes were found to
strongly affect macrophage cell signaling and functions, similarly to whole
parasites. Importantly, these vesicles were shown to be pro-inflammatory, capable
to recruit neutrophils at their inoculation site exacerbating the pathology. In
this review, we provide the most recent insights on the role of exosomes and
other virulence factors, especially the surface protease GP63, in Leishmania-host
interactions, deepening our knowledge on leishmaniasis and paving the way for the
development of new therapeutics.
PMID- 27499213
TI - RNAi-mediated HOXD3 knockdown inhibits growth in human RKO cells.
AB - Numerous studies have shown that the multifunctional Homeobox-containing (HOX) D3
gene is involved in various physiological and pathological processes. To
elucidate the role and mechanism of HOXD3 in colorectal cancer (CRC), we measured
its expression in five CRC cell lines. After determining that HOXD3 was highly
expressed in the human RKO cancer cell line, we used lentiviral-mediated small
interfering RNAs (siRNAs) to knock down HOXD3 expression and assessed
proliferation, cell cycle distribution, apoptosis and colony formation using cell
proliferation, flow cytometric, and colony formation assays. The expression of
HOXD3 was strongly suppressed in the RKO cells infected with the lentiviruse
expressing an HOXD3 short hairpin RNA (shRNA). The downregulation of HOXD3
expression in RKO cells significantly decreased proliferation and colony
formation, and increased apoptosis in vitro, compared to the cells infected with
the mock control (p<0.01). Moreover, specific downregulation of HOXD3 led to the
accumulation of cells at the G2 phase of the cell cycle. Our findings revealed
that the HOXD3 gene promotes CRC cell growth and plays a pivotal role in the
development and survival of malignant human colorectal cancer cells.
PMID- 27499214
TI - Noninvasive Cardiac Output Estimation by Inert Gas Rebreathing in Mechanically
Ventilated Pediatric Patients.
AB - OBJECTIVE: To assess the feasibility and accuracy of inert gas rebreathing (IGR)
pulmonary blood flow (Qp) estimation in mechanically ventilated pediatric
patients, potentially providing real-time noninvasive estimates of cardiac
output. STUDY DESIGN: In mechanically ventilated patients in the pediatric
catheterization laboratory, we compared IGR Qp with Qp estimates based upon the
Fick equation using measured oxygen consumption (VO2) (FickTrue); for context, we
compared FickTrue with a standard clinical short-cut, replacing measured with
assumed VO2 in the Fick equation (FickLaFarge, FickLundell, FickSeckeler). IGR Qp
and breath-by-breath VO2 were measured using the Innocor device. Sampled
pulmonary arterial and venous saturations and hemoglobin concentration were used
for Fick calculations. Qp estimates were compared using Bland-Altman agreement
and Spearman correlation. RESULTS: The final analysis included 18 patients aged 4
23 years with weight >15 kg. Compared with the reference FickTrue, IGR Qp
estimates correlated best and had the least systematic bias and narrowest 95%
limits of agreement (results presented as mean bias +/-95% limits of agreement):
IGR -0.2 +/- 1.1 L/min, r = 0.90; FickLaFarge +0.7 +/- 2.2 L/min, r = 0.80;
FickLundell +1.6 +/- 2.9 L/min, r = 0.83; FickSeckeler +0.8 +/- 2.5 L/min, r =
0.83. CONCLUSIONS: IGR estimation of Qp is feasible in mechanically ventilated
patients weighing >15 kg, and agreement with FickTrue Qp estimates is better for
IGR than for other Fick Qp estimates commonly used in pediatric catheterization.
IGR is an attractive option for bedside monitoring of Qp in mechanically
ventilated children.
PMID- 27499215
TI - Time Perception during Neonatal Resuscitation.
AB - OBJECTIVE: To assess the accuracy of time perception during a simulated complex
neonatal resuscitation. STUDY DESIGN: Participants in 5 neonatal resuscitation
program courses were directly involved in a complex simulation scenario. They
were asked to assume the role of team leader, assistant 1, or assistant 2. At the
end of the scenario, each participant completed a questionnaire on perceived time
intervals for key resuscitation interventions. During the scenario, actual times
were documented by an external observer and video recorded for later review. In
addition, participants were asked to evaluate their self-perceived level of
stress and preparation. RESULTS: Health care providers (68 physicians and 40
nurses) were involved in 36 scenarios. Perceived time intervals for the
initiation of key resuscitation interventions were shorter than the actual time
intervals, regardless of the participant's role in the scenario. Self-assessed
levels of stress and preparation did not influence time perception. CONCLUSIONS:
Health care providers underestimate the passage of time, irrespective of their
role in a simulated complex neonatal resuscitation. Participant's self-assessed
levels of stress and preparation were not related to the accuracy of their time
perception. These findings highlight the importance of assigning a dedicated
individual to document interventions and the passage of time during a neonatal
resuscitation.
PMID- 27499216
TI - Impact of Early-Onset Acute Otitis Media on Multiple Recurrences and Associated
Health Care Use.
AB - OBJECTIVE: To quantify the critical age period of first episode of acute otitis
media (AOM) and its consequences for AOM recurrences and AOM health care use.
STUDY DESIGN: Children enrolled in the Wheezing-Illnesses-STudy-LEidsche-Rijn
cohort with at least 1 episode of AOM documented in their primary care health
record before 2 years of age were followed until 6 years of age. Data on episodes
of AOM and associated primary care consultations, antibiotic prescriptions, and
specialist referrals were retrieved. Regression models assessed the presence and
shape of the associations between age of first AOM and subsequent episodes of AOM
and health care use. RESULTS: A total of 796 of 2026 children (39%) experienced a
first AOM before 2 years of age. Each month decrease in age at first AOM in the
first 2 years of life increased the risk of developing recurrent AOM (>=3 AOM
episodes in 6 months or >= 4 in 1 year) linearly by 6% (adjusted risk ratio:
1.06; 95% CI: 1.02-1.10). For first AOM occurring before 9 months, the cumulative
6-year primary care consultation rate increased by 8% (adjusted incidence rate
ratio: 1.08; 95% CI: 1.03-1.15) and the associated specialist referral increased
by 16% (adjusted risk ratio: 1.16; 95% CI: 1.07-1.27) for each month decrease in
age. No associations were found between age at first AOM and total AOM episodes
or antibiotic prescriptions. CONCLUSIONS: The association between earlier age of
first AOM and recurrent AOM as well as total health care use during childhood is
particularly strong before 9 months of age.
PMID- 27499217
TI - Diagnosis and Treatment of Systemic Juvenile Idiopathic Arthritis.
PMID- 27499218
TI - Relationship of Cardiac Structure and Function to Cardiorespiratory Fitness and
Lean Body Mass in Adolescents and Young Adults with Type 2 Diabetes.
AB - OBJECTIVE: To investigate the relationships of cardiac structure and function
with body composition and cardiorespiratory fitness (CRF) among adolescents with
type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and
Youth study. STUDY DESIGN: Cross-sectional evaluation of 233 participants (median
age 18.3 [min-max 12.4-24.2] years, 63% females, median hemoglobin A1c 6.8%) who
had echocardiography measurements of left ventricular (LV) mass, ejection
fraction, left atrial dimensions, LV diastolic function (early transmitral flow
velocity to early mitral annular velocity ratio from tissue Doppler imaging), and
right ventricular function (tricuspid annular plane systolic excursion [TAPSE])
and body composition (dual-energy x-ray absorptiometry) and CRF (cycle ergometry
determination of physical work capacity at heart rate of 170 beats per minute).
RESULTS: LV mass correlated positively with CRF (r = 0.5, P < .0001), lean body
mass (LBM) (r = 0.7, P < .0001), and fat mass (FM) (r = 0.2, P = .00047); LV
ejection fraction did not. Early transmitral flow velocity to early mitral
annular velocity was positively related to FM (r = 0.14, P = .03) and % body fat
(r = 0.18, P = .007), and left atrial internal diameter correlated with FM (r =
0.4, P < .0001), LBM (r = 0.3, P < .001), and CRF (r = 0.2, P = .0033). TAPSE
weakly correlated with CRF (r = 0.2, P = .0014) and LBM (r = 0.13, P < .05) but
not with FM. In multivariable regression analyses, LBM (beta = 2.13, P < .0001)
and CRF (beta = 0.023, P = .008) were related to LV mass independent of race,
sex, age, hemoglobin A1c, hypertension, smoking, and diabetes medications. CRF
(beta = 0.0002, P = .0187) and hemoglobin A1c (beta = -0.022, P = .0142) were
associated with TAPSE. CONCLUSIONS: In youth with type 2 diabetes, LV size is
related to physical fitness. LV ejection fraction is within normal limits. LV
diastolic function is inversely related to FM. Greater fitness may counteract
adverse effects of poor glycemic control on right ventricular function. TRIAL
REGISTRATION: ClinicalTrials.gov:NCT00081328.
PMID- 27499219
TI - Rice (Oryza sativa) Laccases Involved in Modification and Detoxification of
Herbicides Atrazine and Isoproturon Residues in Plants.
AB - Atrazine (ATR) and isoproturon (IPU) as herbicides have become serious
environmental contaminants due to their overuse in crop production. Although ATR
and IPU in soils are easily absorbed by many crops, the mechanisms for their
degradation or detoxification in plants are poorly understood. This study
identified a group of novel genes encoding laccases (EC 1.10.3.2) that are
possibly involved in catabolism or detoxification of ATR and IPU residues in
rice. Transcriptome profiling shows at least 22 differentially expressed laccase
genes in ATR/IPU-exposed rice. Some of the laccase genes were validated by RT-PCR
analysis. The biochemical properties of the laccases were analyzed, and their
activities in rice were induced under ATR/IPU exposure. To investigate the roles
of laccases in degrading or detoxifying ATR/IPU in rice, transgenic yeast cells
(Pichia pastoris X-33) expressing two rice laccase genes (LOC_Os01g63180 and
LOC_Os12g15680) were generated. Both transformants were found to accumulate less
ATR/IPU compared to the control. The ATR/IPU-degraded products in the transformed
yeast cells using UPLC-TOF-MS/MS were further characterized. Two metabolites,
hydroxy-dehydrogenated atrazine (HDHA) and 2-OH-isopropyl-IPU, catalyzed by
laccases were detected in the eukaryotic cells. These results indicate that the
laccase-coding genes identified here could confer degradation or detoxification
of the herbicides and suggest that the laccases could be one of the important
enzymatic pathways responsible for ATR/IPU degradation/detoxification in rice.
PMID- 27499220
TI - Pathophysiology of acute coronary syndromes in the elderly.
AB - Elderly patients represent an important proportion of the acute coronary syndrome
(ACS) population. Furthermore, this group of ACS patients is continuously growing
because of the progressive ageing of the population. The ageing process implies
marked changes in patient physiology that directly impact in their risk. However,
there is a differential distribution in the risk of elderly patients, revealing
the existence of a discrepancy between the chronological and the "biological
age". This discrepancy has highlighted the need of performing individual risk
assessment in order to identify those patients at higher risk. In addition, the
lack of representation of elderly patients in clinical trials leads to the
underutilization of evidence-based therapies in this group of patients. All these
factors influence not only the high prevalence of ACS presentation in the elderly
but also their worse prognosis after suffering an ischaemic event. Herein we will
explore the pathophysiological mechanisms behind the age-related changes at the
vascular and the cardiac level that explain the high risk of elderly subjects of
suffering ACS and their worse prognosis.
PMID- 27499221
TI - Oral sirolimus: A possible treatment for refractory angina pectoris in the
elderly.
AB - Refractory angina pectoris (RAP) is a clinical problem, frequently encountered in
the elderly, associated with high health-care costs. Until recently, the goal of
RAP treatment aimed at improving the quality of life (QoL) because it was thought
that mortality rates were not different between stable angina pectoris and RAP.
Our purpose was at determining whether any mortality rate difference exists and
whether any novel therapeutical solution might be translated into clinical
practice. We therefore performed a literature review to assess current optimal
treatment of RAP patients, including all studies involving the use of oral
sirolimus and stents, although no consistent evidence was found for any specific
treatment to improve survival, apart from minor QoL amelioration. A large
mortality difference was seen between RAP and stable angina pectoris. On the
other hand, therapeutic approaches to RAP patients showed frequent complications
and several contraindications, depending on the procedure. We propose to inhibit
instead of stimulating angiogenesis, by giving oral sirolimus, an
immunosuppressive drug, thereby decreasing the atherosclerotic process and its
evolution. Sirolimus was shown to decrease left ventricular mass (thus indirectly
decreasing myocardial oxygen needs and consumption). It might stop and, in some
cases, even enable regression of plaque progression. Sirolimus side effects are
mild to moderate and wash-out rapidly at treatment discontinuation. Compared with
current therapies sirolimus treatment is more health-care cost efficient. It
should be important to design a trial in RAP patients powered to reduce mortality
and QoL increase.
PMID- 27499222
TI - The no-reflow phenomenon in the young and in the elderly.
AB - BACKGROUND: The objectives of this study were to evaluate the incidence of no
reflow as independent predictor of adverse events and to assess whether baseline
pre-procedural treatment options may affect clinical outcomes. METHODS: Data were
derived from the ISACS-TC registry (NCT01218776) from October 2010 to January
2015. No-reflow was defined as post-PCI TIMI flow grades 0-1, in the absence of
post-procedural significant (>=25%) residual stenosis, abrupt vessel closure,
dissection, perforation, thrombus of the original target lesion, or epicardial
spasm. The outcome measure was in-hospital mortality. RESULTS: No-reflow was
identified in 128 of 5997 patients who have undergone PCI (2.1%). On multivariate
analysis, patients with no-reflow were more likely to be older (OR: 1.20, 95% CI:
1.01-1.44), to have a history of hypercholesterolemia (OR: 1.95, 95% CI: 1.31
2.91) and to be admitted with a diagnosis of STEMI (OR: 2.96, 95% CI: 1.85-4.72).
Angiographic characteristics associated with no-reflow phenomenon were: stenosis
>=50% of the right coronary artery, presence of multivessel disease and pre
procedural TIMI blood flow grades 0-1. No-reflow was highly predictive of in
hospital mortality (17.2% vs. 4.2%; adjusted OR: 4.60, 95% CI: 2.61-8.09).
Administration of pre-procedural unfractioned heparin or 600mg clopidogrel
loading dose was associated with less incidence of no-reflow (OR: 0.65, 95% CI:
0.43-0.99 and 0.61, 95% CI: 0.37-1.00, respectively). Aspirin, enoxaparin, and
300mg clopidogrel loading dose, did not significantly impact the occurrence of
the no-reflow. CONCLUSIONS: We found that pre-procedural administration of 600mg
loading dose of clopidogrel and/or unfractioned heparin is associated with
reduced incidence of no-reflow.
PMID- 27499223
TI - Immunological complications of blood transfusions.
AB - Most adverse blood transfusion (BT) events are immune-mediated and in the
majority of severe reactions antibodies can be identified as causal factors.
Alloimmunization not only causes symptomatic reactions, transfused cells can also
be (silently) destroyed. Immunization by BT can contribute to hemolytic disease
of the newborn as well as to allograft rejection after transplantation.
Reversely, pregnancy and transplantation may evoke immunity hampering transfusion
therapy. Besides causing mortality and morbidity, alloimmunization has a huge
economic impact. Transfusion reactions prolong hospital stay, require diagnostic
tests and complex donor selection procedures and create the need for typed donor
registries. In the 1970s, Opeltz and colleagues described that pre
transplantation BT impaired rejection of renal transplants. Leukocytes were
essential for this immunosuppressive BT effect that raised concern about negative
effects on cancer growth and resistance against infections. Studies on the
mechanism were however preliminary abandoned when calcineurin inhibitors for
prevention of graft rejection became available and since all blood products
underwent leukoreduction in most countries as precautionary measure against
transmission of variant Creutzfeldt-Jacob disease. Whether current leukoreduced
BT are immunosuppressive and for which patients or circumstances this may
contribute to worse outcome, is unknown. The last decades of the previous
century, leukoreduction of cellular blood products for leukemia patients
significantly reduced the incidence of immunological platelet transfusion
refractoriness. The first decade of this century the avoidance of plasma- and
platelet-products from females, that may contain donor-derived leukocyte
antibodies, decreased transfusion related acute lung injury (TRALI) by more than
30%. These were major achievements. Challenge for the near future is to further
reduce alloimmunization in particular against red blood cells (RBC) as a cause of
severe hemolytic transfusion reactions and problems to find compatible donors.
This can be achieved by extended matching. Inventory limitations prevent to match
all BT for clinically relevant RBC antigens. A (European-wide) registration of
clinical and genetic risk factors associated with alloimmunization could support
effective use of matched blood products.
PMID- 27499224
TI - [Upper gastrointestinal bleeding in portal hypertensive gastropathy reveals a
wandering spleen].
PMID- 27499225
TI - [Research on usual care: Methodological issues].
PMID- 27499226
TI - Patient safety: The pharmacist's contribution to a multidisciplinary Internal
Medicine patient-care team.
PMID- 27499228
TI - Smartphone addiction proneness in relation to sleep and morningness-eveningness
in German adolescents.
AB - Background Mobile phones are an important part of adolescents' life. In this
study, the relationships among smartphone addiction, age, gender, and chronotype
of German adolescents were examined. Materials and methods Two studies focused on
two different measures of smartphone addiction. The Smartphone Addiction
Proneness Scale (SAPS) was applied to 342 younger adolescents (13.39 +/- 1.77;
176 boys, 165 girls, and 1 not indicated) in Study 1 and the Smartphone Addiction
Scale was applied to 208 older adolescents (17.07 +/- 4.28; 146 girls and 62
boys) in Study 2, both samples in southwest Germany. In addition, a demographic
questionnaire and the Composite Scale of Morningness (CSM) and sleep measures
were implemented. Results The most remarkable result of this study was that
morningness-eveningness (as measured by CSM scores) is an important predictor for
smartphone addiction; even stronger than sleep duration. Evening oriented
adolescents scored higher on both smartphone addiction scales. In addition,
gender is an important predictor for smartphone addiction and girls are more
prone to become addicted. In addition, while sleep duration on weekdays
negatively predicted SAPS, age, sleep duration on weekends, and midpoint of sleep
on weekdays and weekends did not predicted smartphone addiction in both scales.
The analysis of covariance revealed statistically significant effects of the
covariates gender and age in both studies, as well as the main effect of
chronotype. According to the t-test results, girls had higher scores than boys in
smartphone addiction. Conclusion Evening types and girls are more prone to become
smartphone addicted.
PMID- 27499227
TI - Predictors and patterns of problematic Internet game use using a decision tree
model.
AB - Background and aims Problematic Internet game use is an important social issue
that increases social expenditures for both individuals and nations. This study
identified predictors and patterns of problematic Internet game use. Methods Data
were collected from online surveys between November 26 and December 26, 2014. We
identified 3,881 Internet game users from a total of 5,003 respondents. A total
of 511 participants were assigned to the problematic Internet game user group
according to the Diagnostic and Statistical Manual of Mental Disorders Internet
gaming disorder criteria. From the remaining 3,370 participants, we used
propensity score matching to develop a normal comparison group of 511
participants. In all, 1,022 participants were analyzed using the chi-square
automatic interaction detector (CHAID) algorithm. Results According to the CHAID
algorithm, six important predictors were found: gaming costs (50%), average
weekday gaming time (23%), offline Internet gaming community meeting attendance
(13%), average weekend and holiday gaming time (7%), marital status (4%), and
self-perceptions of addiction to Internet game use (3%). In addition, three
patterns out of six classification rules were explored: cost-consuming,
socializing, and solitary gamers. Conclusion This study provides direction for
future work on the screening of problematic Internet game use in adults.
PMID- 27499229
TI - Curcumin causes DNA damage and affects associated protein expression in HeLa
human cervical cancer cells.
AB - Cervical cancer is one of the most common cancers in women worldwide and it is a
prominent cause of cancer mortality. Curcumin is one of the major compounds from
Turmeric and has been shown to induce cytotoxic cell death in human cervical
cancer cells. However, there is no study to show curcumin induced DNA damage
action via the effect on the DNA damage and repair protein in cervical cancer
cells in detail. In this study, we investigated whether or not curcumin induced
cell death via DNA damage, chromatin condensation in human cervical cancer HeLa
cells by using comet assay and DAPI staining, respectively, we found that
curcumin induced cell death through the induction of DNA damage, and chromatin
condensation. Western blotting and confocal laser microscopy examination were
used to examine the effects of curcumin on protein expression associated with DNA
damage, repair and translocation of proteins. We found that curcumin at 13 uM
increased the protein levels associated with DNA damage and repair, such as O6
methylguanine-DNA methyltransferase, early-onset breast cancer 1 (BRCA1),
mediator of DNA damage checkpoint 1, p-p53 and p-H2A.XSer140 in HeLa cells.
Results from confocal laser systems microscopy indicated that curcumin increased
the translocation of p-p53 and p-H2A.XSer140 from cytosol to nuclei in HeLa
cells. In conclusion, curcumin induced cell death in HeLa cells via induction of
DNA damage, and chromatin condensation in vitro.
PMID- 27499230
TI - Adsorption Behavior of Metasilicate on N-Methyl d-Glucamine Functional Groups and
Associated Silicon Isotope Fractionation.
AB - Significant isotope fractionation of silicon provides a powerful geochemical
tracer for biological and physicochemical processes in terrestrial and marine
environments. The exact mechanism involved in silicon uptake as part of the
biological process is not well known. The silicon uptake in biological processes
is investigated using silicate adsorption onto the N-methylglucamine functional
group (sugarlike structure, abbreviated as L) of Amberlite IRA-743 resin as an
analogue of the formation of silicate-sugar complexes in plants. This study
provides new evidence that certain sugars can react readily with basic silicic
acid to form sugar-silicate chelating complexes, and the equilibrium adsorption
behavior of silicate can be well described by the Langmuir isotherm with a Gibbs
free energy (DeltaG) of -11.94 +/- 0.21 kJ.mol(-1) at 293 K. The adsorption
kinetics corresponds well to a first-order kinetic model in which the adsorption
rate constant ka of 1.25 * 10(-4) s(-1) and the desorption rate constant kd of
4.00 * 10(-6) s(-1) are obtained at 293 K. Both ka and kd increase with
increasing temperature. The bonding configurations of silicate-sugar complexes
imply the principal coordination complex of hexacoordinated silicon (silicon/L =
1:3) in the liquid phase and the dominant tetracoordinated silicon in the solid
phase. Similar to those of many natural processes, the biological uptake via the
sugar-silicate chelating complexes favors the preferential enrichment of light Si
isotopes into solids, and the Rayleigh model controls the dynamic isotope
fractionation with an estimated silicon isotope fractionation factor (i.e.,
alphasolid-solution = [Formula: see text]) of 0.9971. This study advanced the
fundamental understanding of the dynamic isotope fractionation of silicon during
silicon cycling from the lithosphere to the biosphere and hydrosphere in
surficial processes.
PMID- 27499231
TI - Concentric dual pi aromaticity in bowl-like B30 cluster: an all-boron analogue of
corannulene.
AB - A chemical bonding model is presented for the bowl-like C5v B30 global-minimum
cluster with a central pentagonal hole. The B30 cluster is composed of three
concentric boron rings: first B5, second B10, and third B15. The first and second
B rings constitute an inner double-chain ribbon and support a delocalized pi
sextet. The second and third rings form an outer double-chain ribbon, where 14pi
delocalized electrons are situated. The unique pi systems lead to concentric dual
pi aromaticity for B30, a concept established from concerted computational data
on the bases of canonical molecular orbital (CMO) analysis, adaptive natural
density partitioning (AdNDP), nucleus-independent chemical shifts (NICS), and
natural charge calculations. A proposal is put forward that the bowl-like B30
cluster is an exact all-boron analogue of corannulene (C20H10), a fragment of C60
fullerene. The bonding nature of corannulene is revisited and fully elucidated
herein. A comparison of the bonding patterns in bowl-like C5v B30 cluster and two
other structural isomers (Cs and C1) unravels the mechanism as to why the
defective hole prefers to be positioned at the center.
PMID- 27499232
TI - Two-coordinate terminal zinc hydride complexes: synthesis, structure and
preliminary reactivity studies.
AB - The first examples of essentially two-coordinate, monomeric zinc hydride
complexes, LZnH (L = -N(Ar)(SiR3)) (Ar = C6H2{C(H)Ph2}2R'-2,6,4; R = Me, R' =
Pr(i) (L'); R = Pr(i), R' = Me (L*); R = Pr(i), R' = Pr(i) (L(?))) have been
prepared and shown by crystallographic studies to have near linear N-Zn-H
fragments. The results of computational studies imply that any PhZn interactions
in the compounds are weak at best. Preliminary reactivity studies reveal the
compounds to be effective for the stoichiometric hydrozincation and catalytic
hydrosilylation of carbonyl compounds.
PMID- 27499233
TI - CENPs and Sweet Nucleosomes Face the FACT.
AB - Chaperones mediate vital interactions between histones and DNA during chromatin
assembly and reorganization. Two recent studies reveal novel substrates for the
essential and conserved histone chaperone FAcilitates Chromatin Transcription
(FACT). Prendergast et al. show that FACT helps deposit important histone-fold
proteins on centromeres. Raj et al. find that FACT preferentially binds O
GlcNAcylated nucleosomes, suggesting that FACT may contribute to nutrient
regulated cellular programs.
PMID- 27499234
TI - Linking Long Noncoding RNA Localization and Function.
AB - Recent studies have revealed the regulatory potential of many long noncoding RNAs
(lncRNAs). Most lncRNAs, like mRNAs, are transcribed by RNA polymerase II and are
capped, polyadenylated, and spliced. However, the subcellular fates of lncRNAs
are distinct and the mechanisms of action are diverse. Investigating the
mechanisms that determine the subcellular fate of lncRNAs has the potential to
provide new insights into their biogenesis and specialized functions.
PMID- 27499235
TI - A new animal model containing human SCARB2 and lacking stat-1 is highly
susceptible to EV71.
AB - Enterovirus 71 (EV71) is a major threat to children worldwide. Children infected
with EV71 could develop subclinical infection and hand-foot-and -mouth disease
(HFMD). In severe cases, patients could develop encephalitis, paralysis,
pulmonary edema, and death. A more user-friendly and robust animal model is
essential to investigating EV71 pathogenesis. Here, we established a hybrid
(hSCARB2(+/+)/stat-1(-/-)) mouse strain from crossbreeding SCARB2 transgenic and
stat-1 KO mice, and compared the susceptibilities to EV71 infection and
pathogenesis between parental and hybrid mice. Virus-encoded VP1 protein can be
detected in the streaking nerve fibers in brain and spinal cord. This hybrid
mouse strain at 2-week-old age can still be infected with different genotypes of
EV71 at 1000-fold lower titer via an ip route. Infected hybrid mice developed
earlier onset of CNS disease, paralysis, and death at a higher incidence. These
advantages of this novel model meet the urgent need from the scientific community
in basic and preclinical research in therapeutics and pathogenesis.
PMID- 27499236
TI - Organ-specific radiation-induced cancer risk estimates due to radiotherapy for
benign pigmented villonodular synovitis.
AB - Pigmented villonodular synovitis (PVNS) is a benign disease affecting synovial
membranes of young and middle-aged adults. The aggressive treatment of this
disorder often involves external-beam irradiation. This study was motivated by
the lack of data relating to the radiation exposure of healthy tissues and
radiotherapy-induced cancer risk. Monte Carlo methodology was employed to
simulate a patient's irradiation for PVNS in the knee and hip joints with a 6 MV
photon beam. The average radiation dose received by twenty-two out-of-field
critical organs of the human body was calculated. These calculations were
combined with the appropriate organ-, age- and gender-specific risk coefficients
of the BEIR-VII model to estimate the lifetime probability of cancer development.
The risk for carcinogenesis to colon, which was partly included in the treatment
fields used for hip irradiation, was determined with a non-linear mechanistic
model and differential dose-volume histograms obtained by CT-based 3D
radiotherapy planning. Risk assessments were compared with the nominal lifetime
intrinsic risk (LIR) values. Knee irradiation to 36 Gy resulted in out-of-field
organ doses of 0.2-24.6 mGy. The corresponding range from hip radiotherapy was
1.2-455.1 mGy whereas the organ equivalent dose for the colon was up to 654.9
mGy. The organ-specific cancer risks from knee irradiation for PVNS were found to
be inconsequential since they were at least 161.5 times lower than the LIRs
irrespective of the patient's age and gender. The bladder and colon cancer risk
from radiotherapy in the hip joint was up to 3.2 and 6.6 times smaller than the
LIR, respectively. These cancer risks may slightly elevate the nominal incidence
rates and they should not be ignored during the patient's treatment planning and
follow-up. The probabilities for developing any other solid tumor were more than
20 times lower than the LIRs and, therefore, they may be considered as small.
PMID- 27499237
TI - Cancer-associated fibroblast suppresses killing activity of natural killer cells
through downregulation of poliovirus receptor (PVR/CD155), a ligand of activating
NK receptor.
AB - Cancer-associated fibroblasts (CAFs) play an important role in cancer expansion
and progression in tumor microenvironment (TME), via both direct and indirect
interactions. Natural killer (NK) cells play a crucial role in anticancer
immunity. We investigated the inhibitory effects of CAFs on NK cell activity.
CAFs were isolated from endometrial cancer tissue, while normal endometrial
fibroblasts (NEFs) were obtained from normal endometrium with no pathological
abnormality. NK cells were obtained from allogenic healthy volunteers. CAFs or
NEFs were co-cultured at an NK/fibroblast ratio of 1:1 with or without inserted
membrane. For NK cell activity, K562 cells were cultured as target cells. NK cell
killing activity was determined by calculating the ratio of PI-positive K562
cells in the presence of NK cells co-cultured with fibroblasts versus NK cells
alone. To examine whether NK cell activity was suppressed by IDO pathway, we
inhibited IDO activity using the IDO inhibitor 1-MT. We demonstrated that CAFs
derived from endometrial cancer induced greater suppression of the killing
activity of allogenic NK cells compared with normal endometrial fibroblasts
(NEFs). The suppression of NK cell activity by CAFs was inhibited when a membrane
was inserted between the CAFs and NK cells, but not by 1-MT, an inhibitor of IDO.
We focused on receptor-ligand interactions between CAFs and NK cell and found
that cell-surface poliovirus receptor (PVR/CD155), a ligand of activating NK
receptor DNAM-1, was downregulated in the CAFs compared with NEFs. To confirm
whether PVR downregulation results in the decrease of NK cell-killing activity,
PVR expression in NEFs was knocked down using siRNA against PVR (PVRsi). NK cell
activity was suppressed by co-culture with PVR-knockdown NEFs, to a similar
extent than CAF-induced suppression. CAFs showed increased suppression of NK cell
killing activity compared with NEFs, due to decreased PVR cell surface
expression, a ligand of an NK activating receptor. This study demonstrated a
novel mechanism of suppression of NK cell activity by CAFs in the TME.
PMID- 27499238
TI - Voluntary exercise increases IgA concentration and polymeric Ig receptor
expression in the rat submandibular gland.
AB - Salivary IgA-a primary factor in local immunity of the oral cavity-plays an
important role in maintaining local immune function in the oral cavity and
prevent upper respiratory tract infections. Oral IgA levels are known to
fluctuate in an exercise-dependent manner; thus, we investigated the effects of
voluntary exercise on salivary IgA secretion in rats to better understand the
mechanism by which this occurs. Six-week-old male Wistar rats were placed in
individual cages with or without access to exercise wheels for three weeks.
Notably, animals who engaged in voluntary exercise demonstrated significant
increases in IgA concentration in saliva and submandibular gland tissue, as well
as a markedly higher salivary IgA flow rate. Moreover, active rats also exhibited
elevated polymeric Ig receptor (pIgR) mRNA expression in submandibular gland
tissue. Collectively, these results suggest that voluntary exercise may increase
salivary IgA concentration and boost immune function in the oral cavity.
PMID- 27499239
TI - The diagnostic utility of line probe assays for multidrug-resistant tuberculosis.
AB - Owing to the burden of multidrug-resistant tuberculosis, molecular techniques
have been approved by the WHO for the rapid diagnosis of the same. The objectives
of this prospective, diagnostic study, conducted at Christian Medical College, a
tertiary care center in South India, were to compare the performance of line
probe assay (GenoTypeMTBDRplus) with culture, as well as the Xpert MTB/Rif assay
on sputum samples. Ninety-one consecutive suspects of multidrug-resistant
pulmonary tuberculosis patients from January 2013 to June 2013 were enrolled in
this study and the results of line probe assay compared to culture and Xpert
MTB/Rif. Compared to culture, the assay demonstrated a sensitivity and
specificity of 81.5% (95%CI 67.4-91.1%) and 87.5% (95%CI 71-96.5%) for the
detection of tuberculosis, with sensitivity and specificity of 100% (95%CI 85.2
100%) and 93.8% (95%CI 69.8-99.8%), respectively, for rifampicin resistance. For
isoniazid resistance, sensitivity and specificity were 89.3% (95%CI 71.8-97.7%)
and 100% (95%CI 71.5-100%), respectively. Compared to Xpert MTB/Rif assay, the
assay showed a sensitivity of 80% (95%CI 68.2-88.9%) and specificity of 100%
(95%CI 85.8-100%) for the detection of tuberculosis a sensitivity of 94.3% (95%CI
80.8-99.3%) and specificity of 94.1% (95%CI 71.3-99.9%) for rifampicin resistance
was attained. This assay performed well on smear positive samples, but poorly on
smear negative and scanty samples, and can serve as a rapid diagnostic tool,
particularly in isoniazid monoresistant cases of tuberculosis, which are not
diagnosed by Xpert MTB/Rif.
PMID- 27499240
TI - The benefits of errorless learning for people with amnestic mild cognitive
impairment.
AB - The aim of this study was to explore whether errorless learning leads to better
outcomes than errorful learning in people with amnestic mild cognitive impairment
(MCI), and to examine whether accuracy in error recognition relates to any
observed benefit of errorless over errorful learning. Nineteen participants with
a clinical diagnosis of amnestic MCI were recruited. A word-list learning task
was used and learning was assessed by free recall, cued recall and recognition
tasks. Errorless learning was significantly superior to errorful learning for
both free recall and cued recall. The benefits of errorless learning were less
marked in participants with better error recognition ability. Errorless learning
methods are likely to prove more effective than errorful methods for those people
with MCI whose ability to monitor and detect their own errors is impaired.
PMID- 27499241
TI - Quantity and quality of natural organic matter influence the ecotoxicity of
titanium dioxide nanoparticles.
AB - Nanoparticles' fate is amongst other parameters determined by the quantity and
quality of natural organic matter (NOM). Consequently, the ecotoxicity of
nanoparticles is modified, while only little information is available on the NOM
characteristics triggering this interplay. This study systematically examined how
NOM quantity and quality influences the acute ecotoxicity of titanium dioxide
nanoparticles (nTiO2) towards Daphnia magna. Therefore, two nTiO2 products (A-100
and P25; ~100 nm) were investigated in combination with seven NOM types of
variable quality at four levels each (up to 4.00 mg total organic carbon/L). The
results showed that - independent of the applied nTiO2 product and NOM type -
nTiO2 ecotoxicity decreased up to a factor of >18 with increasing NOM
concentration. More importantly, increasing levels of aromaticity and
hydrophobicity of the NOM decreased the magnitude of toxic effects caused by
nTiO2, which was again independent of the nTiO2 product tested. In the light of
the ubiquitary presence of NOM, the ecotoxicological risk of nTiO2 in surface
waters with high NOM loads is likely moderate. However, interactions of nTiO2 and
NOM in combination with other natural or chemical stressors are not well
understood but seem to be fundamental for a reliable risk assessment of
nanoparticles.
PMID- 27499242
TI - Ultrasonic synthesis of stable oil filled microcapsules using thiolated chitosan
and their characterization by AFM and numerical simulations.
AB - An experimental protocol has been developed for synthesizing stable core-shell
microcapsules using a biopolymer, chitosan, lacking cross-linkable thiol
functional groups. In the first step, thiol moieties were introduced into the
backbone of chitosan using dl-N-acetylhomocysteine thiolactone (AHT). In the
second step, AHT-modified chitosan shelled microcapsules, encapsulating an oil
core, were successfully prepared using high intensity 20 kHz ultrasound. The size
of chitosan and AHT modified chitosan microcapsules was found to be in the range
of 1-15 MUm. The thickness of the microcapsule shell increased with an increase
in thiol content. The mechanical properties of microcapsules were evaluated by
subjecting the microcapsules to compressive forces by colloidal probe AFM. The
stiffness and the Young's modulus of the shell of microcapsules were determined
by analyzing the force versus indentation data using Reissner's theory for
indentation of thin elastic shells. The stiffness of AHT modified chitosan
microcapsules was found to be higher than unmodified chitosan microcapsules. The
viability of microcapsules to be embedded into processed food, pharmaceutical and
cosmetic products was tested via numerical simulations. The confined capsule in
the micro-channel was subjected to linear shear and uniform flows. We used finite
element numerical simulations to determine the deformation of microcapsules in
flow as a function of shear rate and thickness of the shell. The deformation of
capsule was found to be linear with an increase in the shear rate. The
deformation decreased with an increase in the thickness of the shell. Based on
the simulations, we predict that the microcapsules would survive processing
conditions and shear rates used in industrial applications.
PMID- 27499243
TI - Medical complications of psychoactive substances with abuse risks: Detection and
assessment by the network of French addictovigilance centres.
AB - The use of psychoactive substances, whether occasional or regular, can induce a
large number of clinical and/or biological complications. These complications may
be related to the effects of the active substance itself and/or adulterants, but
also to the modalities for use (administrations route, contexts of use). The
detection and evaluation of these potentially severe complications are a public
health issue. Beyond the assessment of the potential for abuse of and dependence
on psychoactive substances, the collection and evaluation of complications
related to the use of the substances are one of the roles of addictovigilance
centres. In this article, the expertise of the French addictovigilance centres in
the detection and assessment of medical complications related to psychoactive
substances, adulterants or route of administration of substances is advanced
through a few recent examples.
PMID- 27499245
TI - A case of atorvastatin-induced solar urticaria.
PMID- 27499246
TI - Is experience the name each surgeon gives to his mistakes?
PMID- 27499247
TI - How can neuroplasticity be utilized to improve neuropathy symptoms?
PMID- 27499244
TI - beta-Catenin C-terminal signals suppress p53 and are essential for artery
formation.
AB - Increased activity of the tumour suppressor p53 is incompatible with
embryogenesis, but how p53 is controlled is not fully understood. Differential
requirements for p53 inhibitors Mdm2 and Mdm4 during development suggest that
these control mechanisms are context-dependent. Artery formation requires
investment of nascent endothelial tubes by smooth muscle cells (SMCs). Here, we
find that embryos lacking SMC beta-catenin suffer impaired arterial maturation
and die by E12.5, with increased vascular wall p53 activity. beta-Catenin
deficient SMCs show no change in p53 levels, but greater p53 acetylation and
activity, plus impaired growth and survival. In vivo, SMC p53 inactivation
suppresses phenotypes caused by loss of beta-catenin. Mechanistically, beta
catenin C-terminal interactions inhibit Creb-binding protein-dependent p53
acetylation and p53 transcriptional activity, and are required for artery
formation. Thus in SMCs, the beta-catenin C-terminus indirectly represses p53,
and this function is essential for embryogenesis. These findings have
implications for angiogenesis, tissue engineering and vascular disease.
PMID- 27499249
TI - Cutaneous involvement in the deep mycoses: A review. Part II -Systemic mycoses.
AB - In the second part of this review on the deep mycoses, we describe the main
systemic mycoses-paracoccidioidomycosis, coccidioidomycosis, histoplasmosis,
mucormycosis, and cryptococcosis-and their cutaneous manifestations. Skin lesions
are only occasionally seen in deep systemic mycoses either directly, when the
skin is the route of entry for the fungus, or indirectly, when the infection has
spread from a deeper focus. These cutaneous signs are often the only clue to the
presence of a potentially fatal infection. As with the subcutaneous mycoses,
early diagnosis and treatment is important, but in this case, even more so.
PMID- 27499248
TI - Regulation of SLD5 gene expression by miR-370 during acute growth of cancer
cells.
AB - SLD5 is a member of the GINS complex, essential for DNA replication in
eukaryotes. It has been reported that SLD5 is involved in early embryogenesis in
the mouse, and cell cycle progression and genome integrity in Drosophila. SLD5
may be involved in malignant tumor progression, but its relevance in human cancer
has not been determined. Here, we found strong SLD5 expression in both human
bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using
small interfering RNA resulted in reduction of cell growth both in vitro and an
in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder
cancer cells result from downregulation of microRNA (miR)-370 that otherwise
suppresses its expression. High level expression of DNA-methyltransferase (DNMT)
1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to
downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced
overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression.
Our findings could contribute to understanding tumorigenic processes and
progression of human bladder cancer, whereby inhibition of SLD5 could represent a
novel strategy to prevent tumor growth.
PMID- 27499250
TI - Frontal Fibrosing Alopecia in Men: Presentations in 12 Cases and a Review of the
Literature.
AB - BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring disease in which the
hairline recedes and the eyebrows can be affected. Usually seen in postmenopausal
women, FFA is much less common in men. OBJECTIVE: To describe the clinical
characteristics of FFA in a case series of men and compare this series to those
reported in the literature. MATERIAL AND METHODS: Men with FFA being treated in
our dermatology department from January 2010 to December 2015 were included
prospectively for this descriptive study. We collected patient information and
clinical and treatment characteristics. RESULTS: Twelve men (mean age, 75 years)
were recruited. Alopecia was the reason for seeking medical care in only 4 cases.
The hairline had receded 3cm on average. Half the patients had facial papules,
and 83% had androgenetic alopecia or hair loss on eyebrows or extremities.
Follicular hyperkeratosis and erythema were present in 66%, and only 25% of the
men reported pruritus. The most commonly prescribed treatments were topical:
corticosteroids in 8 patients (66%) and minoxidil in 4 (33%). CONCLUSIONS: Facial
papules, androgenetic alopecia, and loss of body hair are more often observed in
men with FFA than in women. The men in this series were older on average than in
other FFA case series in the literature, possibly accounting for the higher
prevalence of associated androgenetic alopecia and the fact that most of these
men were seeking care for conditions other than hair loss.
PMID- 27499251
TI - Effect of Substitution on the Aniline Moiety of the GPR88 Agonist 2-PCCA:
Synthesis, Structure-Activity Relationships, and Molecular Modeling Studies.
AB - GPR88, an orphan receptor richly expressed in the striatum, is implicated in a
number of basal ganglia-associated disorders. In order to elucidate the functions
of GPR88, an in vivo probe appropriate for CNS investigation is required. We
previously reported that 2-PCCA was able to modulate GPR88-mediated cAMP
production through a Galphai-coupled pathway. Early structure-activity
relationship (SAR) studies suggested that the aniline moiety of 2-PCCA is a
suitable site for diverse modifications. Aimed at elucidating structural
requirements in this region, we have designed and synthesized a series of
analogues bearing a variety of substituents at the phenyl ring of the aniline
moiety. Several compounds (e.g., 5j, 5o) showed improved or comparable potency,
but have lower lipophilicity than 2-PCCA (clogP 6.19). These compounds provide
the basis for further optimization to probe GPR88 in vivo functions.
Computational studies confirmed the SAR trends and supported the notion that 4'
substituents on the biphenyl ring exit through a largely hydrophobic binding site
to the extracellular loop.
PMID- 27499252
TI - Dynamic Emotional Faces Generalise Better to a New Expression but not to a New
View.
AB - Prior research based on static images has found limited improvement for
recognising previously learnt faces in a new expression after several different
facial expressions of these faces had been shown during the learning session. We
investigated whether non-rigid motion of facial expression facilitates the
learning process. In Experiment 1, participants remembered faces that were either
presented in short video clips or still images. To assess the effect of exposure
to expression variation, each face was either learnt through a single expression
or three different expressions. Experiment 2 examined whether learning faces in
video clips could generalise more effectively to a new view. The results show
that faces learnt from video clips generalised effectively to a new expression
with exposure to a single expression, whereas faces learnt from stills showed
poorer generalisation with exposure to either single or three expressions.
However, although superior recognition performance was demonstrated for faces
learnt through video clips, dynamic facial expression did not create better
transfer of learning to faces tested in a new view. The data thus fail to support
the hypothesis that non-rigid motion enhances viewpoint invariance. These
findings reveal both benefits and limitations of exposures to moving expressions
for expression-invariant face recognition.
PMID- 27499253
TI - Establishment and characterization of a cell line derived from Eptesicus
nilssonii.
AB - Bats of the genus Eptesicus have several non-retroviral RNA virus-derived
sequences in their genomes, among which an endogenous bornavirus-like L element,
named eEBLL-1, was suggested to encode functional proteins in the hosts. However,
the function of eEBLL-1 remains unclear due to a lack of appropriate
investigation tools, such as cultured cells expressing eEBLL-1. Here, we
established a continuous cell line, named HAMOI-EnK cells, from kidney of
Eptesicus nilssonii. HAMOI-EnK cells are robust and could be passaged for at
least 10 months. eEBLL-1 in the genomes of HAMOI-EnK cells retains an intact open
reading frame. Additionally, eEBLL-1 is transcribed in the sense-orientation in
cells. To our knowledge, this is the first report to demonstrate that eEBLL-1 is
transcribed in cultured cells.
PMID- 27499254
TI - A two excited state model to explain the peculiar photobehaviour of a flexible
quadrupolar D-pi-D anthracene derivative.
AB - The peculiar photobehaviour of a symmetrical arylenevinylene anthracene
derivative bearing mild electron donors (alkoxy groups) at the sides of its
structure has been fully comprehended through this study. An investigation into
the effect of solvent polarity and temperature on the stationary fluorescence
spectrum allowed a clear dual emission to be revealed. A further valuable insight
was obtained, thanks to the employment of ultrafast spectroscopies. Fluorescence
up-conversion measurements and the Time Resolved Area Normalised Spectra analysis
provided a clear-cut proof of the presence of two distinct fluorescent states
((1)A* and (1)B*), with (1)A* being responsible for the steady-state emission in
highly polar and viscous media. Femtosecond transient absorption spectra were
acquired in several organic solvents of different polarity and viscosity.
Interestingly, the lifetime of (1)A* was found to be dependent on solvent
viscosity whereas the lifetime of (1)B* showed a trend which matches the change
in solvent polarity. Indeed, the Density functional theory calculations predicted
a structural rearrangement in the fully relaxed lowest excited singlet state. The
(1)A* -> (1)B* transition is thus likely accompanied by large amplitude motions
of the molecular structure, with the (1)B* state also exhibiting a small
intramolecular charge transfer character. The investigated flexible quadrupolar D
pi-D system arouses therefore great interest as a novel material for applications
in organic electronics and photonics.
PMID- 27499255
TI - [Contribution of the physical and rehabilitation medicine in pediatric plastic
surgery].
AB - Physical, non-painful processes guide the scar reshaping in children in order to
prevent growth anomalies due to cutaneous shrinkage. The objective of the
surgical treatment, coordinated with the reeducation care, is to improve the
physical abilities of the skin, to restore the function and avoid the
deformations. Reeducation uses various techniques (i.e. sensitive-motility,
massage and mobilizations) with or without physical agent (water, aspiration and
touch-drive technique). Posture and positioning rely on the small or major aids,
from orthosis to prosthesis. Compression is obtained by the adjustment of aids on
molding and compression garment. Indications of the reeducation treatment depend
on the timing of cutaneous covering and the advance of the healing process. It
also depends on the underlying condition including skin traumas (frictions,
wounds, burns), skin surgeries (purpura fulminans consequences, skin graft
reconstruction after giant nevus resection, malignant lesion or vascular
malformations). The final goal is the rehabilitation and development of the child
and the adolescent in its entire somatopsychic dimension.
PMID- 27499256
TI - [Non syndromic craniosynostosis].
AB - Craniosynostosis are rare congenital malformations of the skull resulting from
the premature fusion of one or several cranial sutures. Prevalence is considered
in approximately 1 on 2000 births. Non syndromic craniosynostosis (NSC) or
isolated form are the most frequent forms (85 % of the cases). They are
classified most of the time according to the synostotic suture(s) and the
engendered cranial deformation: sagittal synostosis or scaphocephaly, metopic
synostosis or trigonocephaly, bicoronal synostosis or brachycephaly, coronal
synostosis or plagiocephaly and oxycephaly. Although the multifactorial origin is
commonly admitted, the precise mechanisms which lead to the premature fusion of a
suture, remain incompletely resolute. The main risks are the intracranial high
blood pressure and its consequences on the psychomotor development, the visual or
respiratory infringement which can require a surgery in emergency. The treatment
is realized by multidisciplinary teams allowing to provide a strategy adapted to
every situation. The decision-making process depends on patient's age, on the
type and severity of the craniosynostosis, and on the patient's health. This
surgery is ideally performed before the age of 1 year and indication only in
morphological purpose is widely recognized to avoid any social damage to the
child. The follow-up is essential and is made throughout the growth in particular
to detect a recurrence or the evolution towards a complex form of
craniosynostosis.
PMID- 27499257
TI - Dermatitis herpetiformis: a cutaneous manifestation of coeliac disease.
AB - Dermatitis herpetiformis (DH) is an itchy blistering skin disease with
predilection sites on elbows, knees, and buttocks. Diagnosis is confirmed by
showing granular immunoglobulin A deposits in perilesional skin. DH is one
manifestation of coeliac disease; the skin symptoms heal with gluten free diet
(GFD) and relapse on gluten challenge. Of the first-degree relatives, 5% may be
affected by either condition. Tissue transglutaminase (TG2) is the autoantigen in
coeliac disease and epidermal transglutaminase (TG3) in DH. Both diseases
conditions exhibit TG2-specific autoantibodies in serum and small bowel mucosa;
patients with DH have IgA-TG3 in the skin. There are some divergencies between
these two phenotypes. One-fourth of DH patients do not have small bowel mucosal
villous atrophy, but virtually all have coeliac-type inflammatory changes. The
skin symptoms respond slowly to GFD. The incidence of coeliac disease is
increasing, whereas the opposite is true for DH. A female predominance is evident
in coeliac disease, while DH may be more common in males. Coeliac disease carries
the risk of small intestinal T-cell lymphoma; in DH B-cell lymphomas at any site
may prevail. Adult coeliac disease carries a slightly increased elevated
mortality risk, whereas in DH, the relative mortality rate is significantly
decreased. Key messages Dermatitis herpetiformis is a cutaneous manifestation of
coeliac disease; both conditions are genetically determined and gluten-dependent.
Gastrointestinal symptoms and the degree of villous atrophy are less obvious in
dermatitis herpetiformis than in coeliac disease. Both show tissue
transglutaminase (TG2) specific autoantibodies in serum and small bowel mucosa.
In addition, TG3-targeted IgA antibodies are found in the skin of DH patients
Both conditions carry an increased elevated risk of lymphoma, in coeliac disease
small intestinal T-cell lymphoma, in dermatitis herpetiformis mainly B-cell
lymphoma at various sites. Coeliac disease is currently eight times more common
that DH; the incidence of DH is decreasing in contrast to that of coeliac
disease, where it is increasing.
PMID- 27499258
TI - Electronically tunable extraordinary optical transmission in graphene plasmonic
ribbons coupled to subwavelength metallic slit arrays.
AB - Subwavelength metallic slit arrays have been shown to exhibit extraordinary
optical transmission, whereby tunnelling surface plasmonic waves constructively
interfere to create large forward light propagation. The intricate balancing
needed for this interference to occur allows for resonant transmission to be
highly sensitive to changes in the environment. Here we demonstrate that
extraordinary optical transmission resonance can be coupled to electrostatically
tunable graphene plasmonic ribbons to create electrostatic modulation of mid
infrared light. Absorption in graphene plasmonic ribbons situated inside metallic
slits can efficiently block the coupling channel for resonant transmission,
leading to a suppression of transmission. Full-wave simulations predict a
transmission modulation of 95.7% via this mechanism. Experimental measurements
reveal a modulation efficiency of 28.6% in transmission at 1,397 cm(-1),
corresponding to a 2.67-fold improvement over transmission without a metallic
slit array. This work paves the way for enhancing light modulation in graphene
plasmonics by employing noble metal plasmonic structures.
PMID- 27499259
TI - Fluoxetine regulates cell growth inhibition of interferon-alpha.
AB - Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to
assist and promote cancer therapy. However, how fluoxetine regulates cellular
signaling to enhance cellular responses against tumor cell growth remains
unclear. In the present study, addition of fluoxetine promoted growth inhibition
of interferon-alpha (IFN-alpha) in human bladder carcinoma cells but not in
normal uroepithelial cells through lessening the IFN-alpha-induced apoptosis but
switching to cause G1 arrest, and maintaining the IFN-alpha-mediated reduction in
G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and
peroxisome proliferator-activated receptor alpha (PPAR-alpha) were involved in
this process. Chemical inhibitions of STAT-1 or PPAR-alpha partially rescued
bladder carcinoma cells from IFN-alpha-mediated growth inhibition via blockades
of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the
presence of fluoxetine. However, the functions of both proteins were not involved
in the control of fluoxetine over apoptosis and maintained the declined G2/M
phase of IFN-alpha. These results indicated that activation of PPAR-alpha and
STAT-1 participated, at least in part, in growth inhibition of IFN-alpha in the
presence of fluoxetine.
PMID- 27499260
TI - Evaluating the healthiness of chain-restaurant menu items using crowdsourcing: a
new method - ERRATUM.
PMID- 27499261
TI - Regulation of DEK expression by AP-2alpha and methylation level of DEK promoter
in hepatocellular carcinoma.
AB - DEK is overexpressed in multiple invasive tumors. However, the transcriptional
regulatory mechanism of DEK remains unclear. In the present study, progressive
type truncation assay indicated that CpG2-2 (-167 bp/+35 bp) was the DEK core
promoter, whose methylation inhibited DEK expression. Bisulfite genomic
sequencing analysis indicated that the methylation levels of the DEK promoter in
normal hepatic cells and tissues were higher than those in hepatocellular
carcinoma (HCC) cells. TFSEARCH result revealed transcription factor binding
sites in CpG2-2. Among the sites, the AP-2alpha binding site showed the most
significant methylation difference; hence, AP-2alpha is a key transcription
factor that regulates DEK expression. Point or deletion mutation of the AP-2alpha
binding site significantly reduced the promoter activity. Chromatin
immunoprecipitation assay demonstrated the binding of AP-2alpha to the core
promoter. Furthermore, knock down of endogenous AP-2alpha downregulated DEK
expression, whereas overexpression of AP-2alpha upregulated DEK expression. Thus,
AP-2alpha is an important transcription factor of DEK expression, which is
correlated with the methylation level of the DEK core promoter in HCC.
PMID- 27499262
TI - Host-guest inclusion system of rhein with polyamine-modified beta-cyclodextrins:
characterization and cytotoxicity.
AB - We report the preparation of inclusion complexes between rhein and four polyamine
modified beta-cyclodextrins, namely amino-beta-cyclodextrins (NH2-betaCD),
ethylenediamine-beta-cyclodextrins (EN-betaCD), diethylenetriamine-beta
cyclodextrins (DETA-betaCD) and triethylenetetramine-beta-cyclodextrins (TETA
betaCD) using suspension method. The solution and solid state forms of the
inclusion complexes of rhein with polyamine-beta-cyclodextrins were characterized
by multiple techniques. Additionally, saturated solution and MTT methods were
implemented to assess the water solubilization and in vitro cytotoxicity of the
inclusion complexes, respectively. The results suggested that rhein was
encapsulated within the CD cavity to form a 1:1 host-guest inclusion complex.
Notably, a significant enhancement of the water solubility and in vitro
cytotoxicity of rhein was found in the form of inclusion complex with polyamine
beta-cyclodextrin.
PMID- 27499263
TI - Legislative provisions related to marriage and divorce of persons with mental
health problems: a global review.
AB - Realization of right to marry by a person is an exercise of personal liberty,
even if concepts of marriage and expectations from such commitment vary across
cultures and societies. Once married, if an individual develops mental illness
the legal system often starts to discriminate against the individual. There is no
doubt that every individual's right to marry or remain married is regulated by
their country's family codes, civil codes, marriage laws, or divorce laws.
Historically mental health condition of a spouse or intending spouse has been of
interest to lawmakers in a number of ways from facilitating divorce to helping
the individual with mental illness. There is no doubt that there are deeply
ingrained stereotypes that persons with mental health problems lack capacity to
consent and, therefore, cannot enter into a marital contract of their own free
will. These assumptions lead to discrimination both in practice and in law.
Furthermore, the probability of mental illness being genetically transmitted and
passed on to offspring adds yet another dimension of discrimination. Thus, the
system may also raise questions about the ability of persons with mental health
problems to care, nurture, and support a family and children. Internationally,
rights to marry, the right to remain married, and dissolution of marriage have
been enshrined in several human rights instruments. Domestic laws were studied in
193 countries to explore whether laws affected the rights of people with mental
illness with respect to marriage; it was found that 37% of countries explicitly
prohibit marriage by persons with mental health problems. In 11% (21 countries)
the presence of mental health problems can render a marriage void or can be
considered grounds for nullity of marriage. Thus, in many countries basic human
rights related to marriage are being flouted.
PMID- 27499264
TI - Integrated solid-state nanopore platform for nanopore fabrication via dielectric
breakdown, DNA-speed deceleration and noise reduction.
AB - The practical use of solid-state nanopores for DNA sequencing requires easy
fabrication of the nanopores, reduction of the DNA movement speed and reduction
of the ionic current noise. Here, we report an integrated nanopore platform with
a nanobead structure that decelerates DNA movement and an insulating polyimide
layer that reduces noise. To enable rapid nanopore fabrication, we introduced a
controlled dielectric breakdown (CDB) process into our system. DNA translocation
experiments revealed that single nanopores were created by the CDB process
without sacrificing performance in reducing DNA movement speed by up to 10
MUs/base or reducing noise up to 600 pArms at 1 MHz. Our platform provides the
essential components for proceeding to the next step in the process of DNA
sequencing.
PMID- 27499265
TI - Proteomic characterization of peroxisome proliferator-activated receptor-gamma
(PPARgamma) overexpressing or silenced colorectal cancer cells unveils a novel
protein network associated with an aggressive phenotype.
AB - Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription
factor of the nuclear hormone receptor superfamily implicated in a wide range of
processes, including tumorigenesis. Its role in colorectal cancer (CRC) is still
debated; most reports support that PPARgamma reduced expression is associated
with poor prognosis. We employed 2-Dimensional Differential InGel Electrophoresis
(2-D DIGE) followed by Liquid Chromatography (LC)-tandem Mass Spectrometry
(MS/MS) to identify differentially expressed proteins and the molecular pathways
underlying PPARgamma expression in CRC progression. We identified several
differentially expressed proteins in HT29 and HCT116 CRC cells and derived clones
either silenced or overexpressing PPARgamma, respectively. In Ingenuity Pathway
Analysis (IPA) they showed reciprocal relation with PPARgamma and a strong
relationship with networks linked to cell death, growth and survival.
Interestingly, five of the identified proteins, ezrin (EZR), isoform C of
prelamin-A/C (LMNA), alpha-enolase (ENOA), prohibitin (PHB) and RuvB-like 2
(RUVBL2) were shared by the two cell models with opposite expression levels,
suggesting a possible regulation by PPARgamma. mRNA and western blot analysis
were undertaken to obtain a technical validation and confirm the expression trend
observed by 2-D DIGE data. We associated EZR upregulation with increased cell
surface localization in PPARgamma-overexpressing cells by flow cytometry and
immunofluorescence staining. We also correlated EZR and PPARgamma expression in
our series of CRC specimens and the expression profiling of all five proteins
levels in the publicly available colon cancer genomic data from Oncomine and
Cancer Genome Atlas (TCGA) colon adenocarcinoma (COAD) datasets. In summary, we
identified a panel of proteins correlated with PPARgamma expression that could be
associated with CRC unveiling new pathways to be investigated for the selection
of novel potential prognostic/predictive biomarkers and/or therapeutic targets.
PMID- 27499267
TI - Non-motor neurological symptoms in patients with amyotrophic lateral sclerosis.
PMID- 27499266
TI - Genomic characterization of the Atlantic cod sex-locus.
AB - A variety of sex determination mechanisms can be observed in evolutionary
divergent teleosts. Sex determination is genetic in Atlantic cod (Gadus morhua),
however the genomic location or size of its sex-locus is unknown. Here, we
characterize the sex-locus of Atlantic cod using whole genome sequence (WGS) data
of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we
identify 166 loci that are associated with sex. These loci are located in six
distinct regions on five different linkage groups (LG) in the genome. The largest
of these regions, an approximately 55 Kb region on LG11, contains the majority of
genotypes that segregate closely according to a XX-XY system. Genotypes in this
region can be used genetically determine sex, whereas those in the other regions
are inconsistently sex-linked. The identified region on LG11 and its surrounding
genes have no clear sequence homology with genes or regulatory elements
associated with sex-determination or differentiation in other species. The
functionality of this sex-locus therefore remains unknown. The WGS strategy used
here proved adequate for detecting the small regions associated with sex in this
species. Our results highlight the evolutionary flexibility in genomic
architecture underlying teleost sex-determination and allow practical
applications to genetically sex Atlantic cod.
PMID- 27499268
TI - Toward Chemical Perfection of Graphene-Based Gene Carrier via Ugi Multicomponent
Assembly Process.
AB - The graphene-based materials with unique, versatile, and tunable properties have
brought new opportunities for the leading edge of advanced nanobiotechnology. In
this regard, the use of graphene in gene delivery applications is still at early
stages. In this study, we successfully designed a new complex of carboxylated
graphene (G-COOH) with ethidium bromide (EtBr) and used it as a nanovector for
efficient gene delivery into the AGS cells. G-COOH, with carboxyl functions on
its surface, in the presence of EtBr, formaldehyde, and cyclohexylisocyanide were
participated in Ugi four component reaction to fabricate a stable amphiphilic
graphene-EtBr (AG-EtBr) composite. The coupling reaction was confirmed by further
analyses with FT-IR, AFM, UV-vis, Raman, photoluminescence, EDS, and XPS. The AG
EtBr nanocomposite was able to interact with a plasmid DNA (pDNA). This
nanocomposite has been applied for transfection of cultured mammalian cells
successfully. Moreover, the AG-EtBr composites showed a remarkable decreased
cytotoxicity in compared to EtBr. Interestingly, the advantages of AG-EtBr in
cell transfection are more dramatic (3-fold higher) than Lipofectamine2000 as a
commercial nonviral vector. To the best of our knowledge, this is the first
report in which EtBr is used as an intercalating agent along with graphene to
serve as a new vehicle for gene delivery application.
PMID- 27499269
TI - Nanoscale studies link amyloid maturity with polyglutamine diseases onset.
AB - The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly
linked to the pathogenesis of several neurodegenerative diseases, including
Huntington's disease. However, the molecular and structural basis underlying the
increased toxicity of aggregates formed by proteins containing expanded polyQ
repeats remain poorly understood, in part due to the size and morphological
heterogeneity of the aggregates they form in vitro. To address this knowledge gap
and technical limitations, we investigated the structural, mechanical and
morphological properties of fibrillar aggregates at the single molecule and
nanometer scale using the first exon of the Huntingtin protein as a model system
(Exon1). Our findings demonstrate a direct correlation of the morphological and
mechanical properties of Exon1 aggregates with their structural organization at
the single aggregate and nanometric scale and provide novel insights into the
molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.
PMID- 27499270
TI - Impaired renal function is associated with recurrence after cryoballoon catheter
ablation for paroxysmal atrial fibrillation: A potential effect of non-pulmonary
vein foci.
AB - BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) are closely
related. The present study aimed to evaluate the association between estimated
glomerular filtration rate (eGFR) and outcomes after cryoballoon catheter
ablation for AF. METHODS: We included a total of 110 patients (64.0+/-10.1 years,
64% men) with paroxysmal AF who underwent second-generation cryoballoon catheter
ablation in this study. Recurrence and change in renal function after ablation
were assessed by stratification of eGFR sub-groups. RESULTS: During a mean follow
up period of 9 months, 20 (18%) patients had AF recurrence after the first
catheter ablation procedure. Multivariate Cox regression analysis showed that
eGFR [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.93-0.99, p=0.047],
non-pulmonary vein (PV) ectopic beats at initial ablation (HR 2.92, 95% CI 1.03
8.27, p=0.043), and history of stroke (HR 7.47, 95% CI 2.30-24.2, p=0.001) were
independent predictors of recurrence after the ablation. Among the CKD groups,
recurrence was found in 7% (1/15), 12% (9/73), and 46% (10/22) of the eGFR
>=90mL/min/1.73m2, eGFR 60-89.9mL/min/1.73m2, and eGFR 30-59.9mL/min/1.73m2
groups, respectively (p=0.001). Kaplan-Meier survival curves demonstrated that
patients with eGFR 30-59.9mL/min/1.73m2 had significantly worse prognosis than
did the other groups (log-rank p<0.001). In addition, non-PV ectopic beats at
initial ablation were detected in 7% (1/15), 14% (10/73), and 50% (11/22) of the
patients among the three CKD groups, respectively (p<0.001). No patients
developed contrast-induced nephropathy after the catheter ablation procedure.
CONCLUSIONS: Low eGFR at baseline was an independent predictor of recurrence
after cryoballoon ablation for paroxysmal AF. The presence of non-PV ectopic
beats was significantly increased in patients with impaired renal function, which
might be associated with a poor outcome.
PMID- 27499271
TI - Reduction of c-kit positive cardiac stem cells in patients with atrial
fibrillation.
AB - BACKGROUND: We aimed to determine expression patterns of cardiac stem cells in
the left atrium (LA) tissue from patients with atrial fibrillation. METHODS: LA
appendages were obtained during open-heart surgery and processed for explant cell
culture and tissue analysis (n=319). The total number of grown cells and c-kit
positive cells were analyzed by flow cytometry after 4 weeks of culture. The
remaining tissue was used for Masson's trichrome staining to determine the area
of the fibrosis. RESULTS: The diameter of the LA, as measured by
echocardiography, was significantly larger in the AF group than in the sinus
rhythm group. Reverse transcription polymerase chain reaction analysis revealed
higher expression of collagen in the AF group and an increase in the expression
of basic fibrosis growth factor and transforming growth factor-2 and -3. Masson's
trichrome staining showed progression of fibrosis in the AF tissue. In addition,
the expression of apoptosis-related genes were significantly higher in AF group.
There was no difference in the expression of connexin-40 between groups, while
the expression of connexin-43 was decreased and that of connexin-45 was increased
in the AF group. The total numbers of grown cells as well as c-kit positive cells
after 4 weeks of cardiac tissue culture were significantly lower in the AF group.
CONCLUSION: Progression of remodeling in LA tissue was observed in AF patients.
The number of c-kit positive cells cultured from LA appendages was reduced in AF
patients, suggesting impairments in self-renewal.
PMID- 27499272
TI - Wogonin inhibits the proliferation and invasion, and induces the apoptosis of
HepG2 and Bel7402 HCC cells through NF-kappaB/Bcl-2, EGFR and EGFR downstream
ERK/AKT signaling.
AB - The anticancer effects of the natural flavonoid, wogonin, have been reported.
However, its molecular mechanisms of action have not yet been fully explored. In
the present study, we aimed to examine the molecular mechanisms of action of
wogonin and its effects on the biological behavior of the HepG2 and Bel7402
hepatocellular carcinoma (HCC) cell lines. We also examined the effects of
wogonin on nuclear factor-kappaB (NF-kappaB)/Bcl-2 and epidermal growth factor
receptor (EGFR) signaling, as well as on downstream pathways of EGFR, namely
extracellular signal-regulated kinase (ERK)/AKT signaling. We found that
treatment with wogonin inhibited the proliferation and invasion, and induced the
apoptosis of the HepG2 and Bel7402 cells. In addition, treatment with wogonin
decreased cyclin D1, cyclin E, CDK4/6, Bcl-2 and matrix metalloproteinase 2
(MMP2) expression, and promoted the cleavage of caspase-3 and caspase-9 in a
concentration-dependent manner. Further experiments revealed that wogonin
inhibited NF-kappaB/Bcl-2 signaling by decreasing the IkappaB and p65
phosphorylation levels. Wogonin also inhibited the activation of the EGFR
(Tyr845) signaling pathway, and that of downstream pathways of EGFR, namely
ERK/AKT/MMP2 signaling. The depletion of EGFR by siRNA partly abolished the
inhibitory effects of wogonin on cyclin D1, MMP2 expression. On the whole, our
our findings demonstrate that wogonin effectively suppresses the proliferation,
invasion and survival of HCC cells through the modulation of the NF-kappaB and
EGFR signaling pathways.
PMID- 27499273
TI - Downstream Migration and Fragmentation of a Spontaneous Calcific Embolus after
Thrombolysis in a Patient with Ischemic Stroke.
AB - We report a successful treatment experience with systemic thrombolysis in a
patient with acute ischemic stroked caused by spontaneous calcific embolus, which
resulted in clinical improvement and embolus fragmentation.
PMID- 27499274
TI - Anteromedial dome impaction in acetabular fractures: Issues and controversies.
PMID- 27499275
TI - Finding Knowledge Gaps in Aerobic Granulation Technology.
AB - This review identifies the knowledge gaps in aerobic granulation technology and
defines some problems for future studies. In particular, extracellular polymeric
substances (EPSs) should be further characterized to understand the
intermolecular interactions among these polymers, the role of chelating agents in
destabilizing EPS ionic bridges needs further elucidation, and early detection of
the quorum-quenching enzymes should be considered to avoid granule segregation
and process failure. Furthermore, the process should be supplemented with
volatile fatty acids as electron donors/carbon sources, and appropriate
anoxic/anaerobic conditions should be provided for enhanced nitrogen and
phosphorus removal. Finally, the biodegradation, bioaccumulation, biosorption,
and mass transfer behaviors of the emerging contaminants within the granules need
further investigation.
PMID- 27499276
TI - Strategies for Derisking Translational Processes for Biomedical Technologies.
AB - Inefficient translational processes for technology-oriented biomedical research
have led to some prominent and frequent failures in the development of many
leading drug candidates, several designated investigational drugs, and some
medical devices, as well as documented patient harm and postmarket product
withdrawals. Derisking this process, particularly in the early stages, should
increase translational efficiency and streamline resource utilization, especially
in an academic setting. In this opinion article, we identify a 12-step guideline
for reducing risks typically associated with translating medical technologies as
they move toward prototypes, preclinical proof of concept, and possible clinical
testing. Integrating the described 12-step process should prove valuable for
improving how early-stage academic biomedical concepts are cultivated, culled,
and manicured toward intended clinical applications.
PMID- 27499277
TI - Textile Processes for Engineering Tissues with Biomimetic Architectures and
Properties.
AB - Textile technologies in which fibers containing biological factors and cells are
formed and assembled into constructs with biomimetic properties have attracted
significant attention in the field of tissue engineering. This Forum article
highlights the most prominent advances of the field in the areas of fiber
fabrication and construct engineering.
PMID- 27499278
TI - Commentary to "Biometry of the hypospadic penis after hormone therapy
(testosterone and estrogen): A randomized double-blind controlled trial".
PMID- 27499279
TI - Spontaneous bladder rupture in non-augmented bladder exstrophy.
AB - OBJECTIVE: Bladder perforation is not commonly described in bladder exstrophy
patients without bladder augmentation. The goal of this study was to identify the
risk factors of spontaneous perforation in non-augmented exstrophy bladders.
METHODS: The study was a retrospective multi-institutional review of bladder
perforation in seven male and two female patients with classic bladder exstrophy
epispadias (E-E). RESULTS: Correction of E-E was performed using Kelly repair in
two and staged repair in seven (Table). Bladder neck repair was performed in
eight patients at a mean age of 6 years. Three patients had additional urethral
surgery. Before rupture, six patients were voiding only per urethra. Two patients
were voiding urethrally but were also performing occasional CIC via a
Mitrofanoff. One patient was performing CIC 3 hourly per urethra. Six were dry
during the day. Six of the patients had lower urinary tract symptoms: five had
frequency and four were straining to void. Two had suffered episodes of urinary
retention. Pre-rupture ultrasound showed that the upper urinary tract was dilated
in four patients. Micturating cystourethrogram was performed in six showing
vesico-ureteral reflux in five. Two had urethral stenosis. Nuclear medicine was
done in three patients with two abnormal differential function. Urodynamics was
performed in two patients with low capacity (100 mL) and hypocompliant (<10)
bladders. Both had high leak point pressures: 60 cmH2O at 100 mL. The mean age at
rupture was 11 years, with a range of 5-20 years. Patients presented with
abdominal pain, associated with signs of intestinal obstruction in seven and
fever in two. Eight patients underwent laparotomy and one prolonged drainage via
SPC. Simple closure was performed in seven and bladder neck closure in one,
because of extension of the rupture inferiorly. All patients recovered well.
Following rupture, five underwent augmentation and Mitrofanoff. One of these
suffered a recurrent rupture. Two other patients refused augmentation and
Mitrofanoff and one of these has since had a subsequent rupture. CONCLUSIONS: The
limitations of this series include the small number of patients and its
retrospective nature, without knowledge of the incidence. Bladder rupture is a
risk even in non-augmented bladder exstrophy. It is potentially life-threatening
and most often requires laparotomy. Rupture occurs because of poor bladder
emptying and/or high pressure. Urodynamics may identify those at risk. CIC with
or without augmentation should not be delayed once poor bladder emptying and/or
high pressure are identified.
PMID- 27499280
TI - Maternal and fetal risk factors for bladder exstrophy: A nationwide Swedish case
control study.
AB - INTRODUCTION: Bladder exstrophy is a rare, congenital, complex malformation where
the underlying cause is largely unknown. Both environmental and genetic
mechanisms are thought to be involved. There are divergent results concerning the
prevalence, birth descriptive data, and potential maternal risk factors for
bladder exstrophy. Few previous studies have reflected nationwide populations,
population registers, or spanned a longer period of time. OBJECTIVE: To describe
and assess bladder exstrophy and the potential maternal risk factors, for a time
period of four decades, by conducting a nationwide register study of bladder
exstrophy in Sweden. METHODS: A matched-design, case-control, linkage-analysis
study nested within the entire pool of live births in Sweden between 1973 and
2011 was performed. Cases with bladder exstrophy were identified using nationwide
population-based birth and health registers. Inclusion criteria were people born
in Sweden with the classification of bladder exstrophy according to the ICD
coding system. Cases were matched with five controls per patient, based on birth
year and sex. Prevalence was assessed and birth descriptive data were compiled.
Potential maternal risk factors were obtained from medical birth registers of
cases and assessed using conditional and multivariate logistic regression models
to obtain odds ratios as a measure of the relative risk. Classification of the
diagnosis in the registers constituted a possible limitation for determining the
correct study population, which demanded strict validation and inclusion
criteria. All data were collected prospectively, thereby avoiding potential
recall bias. RESULTS: The prevalence was calculated to be approximately 3 per
100,000 live births, with a male-to-female ratio of 1.14:1. In 92.5% of the
cases, bladder exstrophy was an isolated malformation without associated major
malformations. However, 41% had had surgery for congenital inguinal hernia and
11% of the male subjects had been operated on for cryptorchidism. A significantly
higher proportion of cases had a birth weight <1500 g compared with controls, but
other characteristics were comparable with controls. High maternal age was the
only significant potential associated maternal risk factor. CONCLUSIONS: One
hundred and twenty children born with bladder exstrophy in Sweden during the last
four decades were identified; this resulted in prevalence in Sweden of 3 per
100,000. The prevalence was stable over time and the sex ratio was equal. Birth
characteristics were comparable to controls, and bladder exstrophy generally
occurred as an isolated malformation without major associated malformations.
Advanced maternal age was the only significant potential maternal risk factor.
PMID- 27499281
TI - ESPU Editorial.
PMID- 27499282
TI - Editorial comment for Protective effect of tunica albuginea incision with tunica
vaginalis flap coverage on tissue damage and oxidative stress following
testicular torsion: Role of duration of ischemia.
PMID- 27499283
TI - Effects of electrode gap and wastewater condition on the performance of microbial
fuel cell coupled constructed wetland.
AB - The effects of electrode gap, PB solution concentration and azo dye on the
wastewater treatment and electricity generation of microbial fuel cell coupled
constructed wetland (CW-MFC) were studied. The electrode gap had obvious
influence on the decolorization, while the influence of PB concentration on the
decolorization was not obvious. The best decolorization efficiency was 91.05% and
was gained when the electrode gap was 13.2 cm. The smaller the electrode gap, the
smaller the ohmic resistance. However, a too small electrode gap would reduce the
electricity generation. The best PB concentration in this study was 50 mM. In the
glucose group, when the PB concentration was 50 mM, the power density was
enhanced to 0.38 W/m3, while the PB concentration was 5 mM, the power density was
only 0.14 W/m3. In the ABRX3 group, when the PB concentration was 50 mM, the
power density was 0.18 W/m3, while when the PB concentration was 5 mM, the power
density was 0.12 W/m3. The electricity generation performance of the CW-MFC was
enhanced with an increase in running time. Long-time running CW-MFC got a higher
cathode potential and a smaller internal resistance.
PMID- 27499284
TI - [Changes in features of diabetes care in Hungary in the period of years 2001
2014. Aims and methods of the database analysis of the National Health Insurance
Fund].
AB - In the last couple of years, database analyses have become increasingly popular
among clinical-epidemiological investigations. In Hungary, the National Health
Insurance Fund serves as central database of all medical attendances in state
departments and purchases of drug prescriptions in pharmacies. Data from in- and
outpatient departments as well as those from pharmacies are regularly collected
in this database which is public and accessible on request. The aim of this
retrospective study was to investigate the database of the National Health
Insurance Fund in order to analyze the diabetes-associated morbidity and
mortality in the period of years 2001-2014. Moreover, data of therapeutic costs,
features of hospitalizations and practice of antidiabetic treatment were
examined. The authors report now on the method of the database analysis. It is to
be hoped that the upcoming results of this investigation will add some new data
to recent knowledge about diabetes care in Hungary. Orv. Hetil., 2016, 157(32),
1259-1265.
PMID- 27499285
TI - [Peripheral arterial disease and diabetes related lower limb amputations.
Presentation of the epidemiological data and the analysis of potentialities in
preventive strategy].
AB - Lower limb amputation as one of the most devastating consequences of peripheral
arterial disease and diabetes mellitus needs peculiar attention. This review aims
at comparing Hungarian and international amputation data. Realizing the great
variability of the global amputation incidence and trends data, the main
determinants of this variety are assessed. These factors involve methodological
differences in reporting, demographic, epidemiological, economic, societal and
cultural variation of the affected populations and differences in the health care
service. The amputation hazard can be considered as an example of lifetime risk
that can be characterized by complex interaction of contionuously changing risk
factor pattern. In that sense an effective preventive strategy planning needs
complex measure implementations that associate with multidisciplinary approach,
timely complex preventive interventions and centralized vascular care. Research
and development on amputation field shows clear priority that can contribute to
the better understanding of this extremely complex scenario with significant
public health consequences. Orv. Hetil., 2016, 157(32), 1266-1274.
PMID- 27499286
TI - [Genetic and epigenetic factors of polycystic ovary syndrome].
AB - The development of polycystic ovary syndrome and its exact pathophysiological
mechanism is still unclear, but environmental and genetic factors likely play a
role. Exposition to teratogenic effects during the prenatal development can lead
to chronic diseases in the postnatal period. This finding confirms the common
familial aggregation as well. A literature search was conducted up to January 1,
2016 for articles dealing with the genetic or epigenetic factors of polycystic
ovary syndrome. This review will discuss the current understanding of the genetic
basis and clinical presentation of this disease. Orv. Hetil., 2016, 157(32), 1275
1281.
PMID- 27499287
TI - [Prognostic significance of the culprit vessel in patients with ST-elevation
myocardial infarction treated with primary coronary intervention].
AB - INTRODUCTION: To the best of the authors' knowledge, very few publications are
available which report on the prognostic significance of the culprit vessel in
patients with ST elevation myocardial infarction treated with successful primary
percutaneous coronary intervention. AIM: The aim of the authors was to obtain
data on the significance of the culprit vessel in patients with ST elevation
myocardial infarction treated successfully by primary percutaneous coronary
intervention. METHOD: The authors performed a retrospective study in 10,763
patients with ST elevation myocardial infarction who underwent successful primary
percutaneous coronary intervention. The culprit vessels were the left main
artery, left anterior descendent artery, left circumflex artery, and right
coronary artery. The authors constructed univariate survival curves for different
culprit vessels and also performed multivariate modelling of time-to-death,
controlling for age, sex, and comorbidities. RESULTS: The majority of the culprit
lesions were found in the left anterior descendent artery (44.3%), the right
coronary artery (40.9%), and the left circumflex artery (13.7%). The culprit
vessel was overall a highly significant (p<0.0001) factor of survival, with right
coronary artery exhibiting a highly significantly better prognosis (hazard ratio
0.69, 95% CI 0.61-0.79, p<0.0001) and left main artery exhibiting a significantly
worse prognosis (hazard ratio 1.56, 95% CI 1.04-2.35, p = 0.0321) than the
reference vessel (left anterior descendent artery). CONCLUSION: These data
demonstrate that the culprit vessel has independent prognostic significance. Orv.
Hetil., 2016, 157(32), 1282-1288.
PMID- 27499288
TI - [Self-citations: the stepchildren of scientometrics?].
AB - Self-references, self-citations are considered by some as the sign of vanity, and
deemed to be omitted from scientometrics analyses. In fact, self-citations reveal
information in the study of scientific communications that is different but not
less valuable than citations received from others. In the practice of self
citation severe ethical issues may emerge that can be bandled by the co-operation
of the authors, editors and publishers. Orv. Hetil., 2016, 157(32), 1289-1293.
PMID- 27499289
TI - [Miscellaneous].
PMID- 27499290
TI - Persistence of Escherichia coli in batch and continuous vermicomposting systems.
AB - Vermicomposting is a biooxidation process in which epigeicearthworms act in
synergy with microbial populations to degrade organic matter. Vermicomposting
does not go through a thermophilic stage as required by North American
legislations for pathogen eradication. We examined the survival of a Green
Fluorescent Protein (GFP) labeled Escherichia coli MG1655 as a model for the
survival of pathogenic bacteria in both small-scale batch and medium-scale
continuously-operated systems to discern the influence of the earthworm Eisenia
fetida, nutrient content and the indigenous vermicompost microbial community on
pathogen abundance. In batch systems, the microbial community had the greatest
influence on the rapid decline of E. coli populations, and the effect of
earthworms was only visible in microbially-impoverishedvermicomposts. No
significant earthworm density-dependent relationship was observed on E. coli
survival under continuous operation. E. coli numbers decreased below the US EPA
compost sanitation guidelines of 10(3)Colony Forming Units (CFU)/g (dry weight)
within 18-21days for both the small-scale batch and medium-scale continuous
systems, but it took up to 51days without earthworms and with an impoverished
microbial community to reach the legal limit. Nutrient replenishment (i.e.
organic carbon) provided by continuous feed input did not appear to extend E.
coli survival. In fact, longer survival of E. coli was noticed in treatments
where less total and labile sugars were available, suggesting that sugars may
support potentially antagonist bacteria in the vermicompost. Total N, pH and
humidity did not appear to affect E. coli survival. Several opportunistic human
pathogens may be found in vermicompost, and their populations are likely kept in
check by antagonists.
PMID- 27499291
TI - Assessing the economics of processing end-of-life vehicles through manual
dismantling.
AB - Most dismantling enterprises in a number of developing countries, such as China,
usually adopt the "manual+mechanical" dismantling approach to process end-of-life
vehicles. However, the automobile industry does not have a clear indicator to
reasonably and effectively determine the manual dismantling degree for end-of
life vehicles. In this study, five different dismantling scenarios and an
economic system for end-of-life vehicles were developed based on the actual
situation of end-of-life vehicles. The fuzzy analytic hierarchy process was
applied to set the weights of direct costs, indirect costs, and sales and to
obtain an optimal manual dismantling scenario. Results showed that although the
traditional method of "dismantling to the end" can guarantee the highest
recycling rate, this method is not the best among all the scenarios. The profit
gained in the optimal scenario is 100.6% higher than that in the traditional
scenario. The optimal manual dismantling scenario showed that enterprises are
required to select suitable parts to process through manual dismantling.
Selecting suitable parts maximizes economic profit and improves dismantling
speed.
PMID- 27499293
TI - Inverting the Topology of a Transmembrane Protein by Regulating the Translocation
of the First Transmembrane Helix.
AB - TM4SF20 (transmembrane 4 L6 family 20) is a polytopic membrane protein that
inhibits proteolytic processing of CREB3L1 (cAMP response element-binding protein
3-like 1), a membrane-bound transcription factor that blocks cell division and
activates collagen synthesis. Here we report that ceramide stimulates CREB3L1
cleavage by inverting the orientation of TM4SF20 in membranes. In the absence of
ceramide, the N terminus of the first transmembrane helix of TM4SF20 is inserted
into the endoplasmic reticulum (ER) lumen. This translocation requires TRAM2
(translocating chain-associated membrane protein 2), a membrane protein
containing a putative ceramide-interacting domain. In the presence of ceramide,
the N terminus of the first transmembrane domain of TM4SF20 is exposed to
cytosol. Consequently, the membrane topology of TM4SF20 is inverted, and this
form of TM4SF20 stimulates CREB3L1 cleavage. In the presence of ceramide,
translocation of TM4SF20 is TRAM2-independent. We designate this mechanism
causing regulated inversion of the membrane topology as "regulated alternative
translocation."
PMID- 27499292
TI - The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity.
AB - CENP-A is a histone variant, which replaces histone H3 at centromeres and confers
unique properties to centromeric chromatin. The crystal structure of CENP-A
nucleosome suggests flexible nucleosomal DNA ends, but their dynamics in solution
remains elusive and their implication in centromere function is unknown. Using
electron cryo-microscopy, we determined the dynamic solution properties of the
CENP-A nucleosome. Our biochemical, proteomic, and genetic data reveal that
higher flexibility of DNA ends impairs histone H1 binding to the CENP-A
nucleosome. Substituting the 2-turn alphaN-helix of CENP-A with the 3-turn alphaN
helix of H3 results in compact particles with rigidified DNA ends, able to bind
histone H1. In vivo replacement of CENP-A with H3-CENP-A hybrid nucleosomes leads
to H1 recruitment, delocalization of kinetochore proteins, and significant
mitotic and cytokinesis defects. Our data reveal that the evolutionarily
conserved flexible ends of the CENP-A nucleosomes are essential to ensure the
fidelity of the mitotic pathway.
PMID- 27499295
TI - DNA Repair Profiling Reveals Nonrandom Outcomes at Cas9-Mediated Breaks.
AB - The repair outcomes at site-specific DNA double-strand breaks (DSBs) generated by
the RNA-guided DNA endonuclease Cas9 determine how gene function is altered.
Despite the widespread adoption of CRISPR-Cas9 technology to induce DSBs for
genome engineering, the resulting repair products have not been examined in
depth. Here, the DNA repair profiles of 223 sites in the human genome demonstrate
that the pattern of DNA repair following Cas9 cutting at each site is nonrandom
and consistent across experimental replicates, cell lines, and reagent delivery
methods. Furthermore, the repair outcomes are determined by the protospacer
sequence rather than genomic context, indicating that DNA repair profiling in
cell lines can be used to anticipate repair outcomes in primary cells. Chemical
inhibition of DNA-PK enabled dissection of the DNA repair profiles into
contributions from c-NHEJ and MMEJ. Finally, this work elucidates a strategy for
using "error-prone" DNA-repair machinery to generate precise edits.
PMID- 27499294
TI - Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase
Activity.
AB - The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter
of microbial PKLs and five human homologs, yet its biochemical activities remain
obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone
(CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice
lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje
cell dysfunction and mild exercise intolerance, recapitulating ARCA2.
Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically
stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although
COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical
protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts
with lipid CoQ intermediates, functions that are likely conserved across all
domains of life. Collectively, our results lend insight into the molecular
activities of the ancient UbiB family and elucidate the biochemical underpinnings
of a human disease.
PMID- 27499297
TI - OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation.
AB - Cell type specification relies on the capacity of undifferentiated cells to
properly respond to specific differentiation-inducing signals. Using genomic
approaches along with loss- and gain-of-function genetic models, we identified
OCT4-dependent mechanisms that provide embryonic stem cells with the means to
customize their response to external cues. OCT4 binds a large set of low
accessible genomic regions. At these sites, OCT4 is required for proper enhancer
and gene activation by recruiting co-regulators and RAR:RXR or beta-catenin,
suggesting an unexpected collaboration between the lineage-determining
transcription factor and these differentiation-initiating, signal-dependent
transcription factors. As a proof of concept, we demonstrate that overexpression
of OCT4 in a kidney cell line is sufficient for signal-dependent activation of
otherwise unresponsive genes in these cells. Our results uncover OCT4 as an
integral and necessary component of signal-regulated transcriptional processes
required for tissue-specific responses.
PMID- 27499296
TI - Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory
Chain Function.
AB - Mitochondria are essential for numerous cellular processes, yet hundreds of their
proteins lack robust functional annotation. To reveal functions for these
proteins (termed MXPs), we assessed condition-specific protein-protein
interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our
data connect MXPs to diverse mitochondrial processes, including multiple aspects
of respiratory chain function. Building upon these observations, we validated
C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly
reduced CI activity, and its depletion is found in an unresolved case of CI
deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the
electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ).
Finally, we identified a dynamic human CoQ biosynthetic complex involving
multiple MXPs whose topology we map using purified components. Collectively, our
data lend mechanistic insight into respiratory chain-related activities and
prioritize hundreds of additional interactions for further exploration of
mitochondrial protein function.
PMID- 27499298
TI - Development and pilot study of an essential set of indicators for general surgery
services.
AB - INTRODUCTION: At present there is a lack of appropriate quality measures for
benchmarking in general surgery units of Spanish National Health System. The aim
of this study is to present the selection, development and pilot-testing of an
initial set of surgical quality indicators for this purpose. METHODS: A modified
Delphi was performed with experts from the Spanish Surgeons Association in order
to prioritize previously selected indicators. Then, a pilot study was carried out
in a public hospital encompassing qualitative analysis of feasibility for
prioritized indicators and an additional qualitative and quantitative three-rater
reliability assessment for medical record-based indicators. Observed inter-rater
agreement, prevalence adjusted and bias adjusted kappa and non-adjusted kappa
were performed, using a systematic random sample (n=30) for each of these
indicators. RESULTS: Twelve out of 13 proposed indicators were feasible: 5
medical record-based indicators and 7 indicators based on administrative
databases. From medical record-based indicators, 3 were reliable (observed
agreement >95%, adjusted kappa index >0.6 or non-adjusted kappa index >0.6 for
composites and its components) and 2 needed further refinement. CONCLUSIONS:
Currently, medical record-based indicators could be used for comparison purposes,
whilst further research must be done for validation and risk-adjustment of
outcome indicators from administrative databases. Compliance results in the
adequacy of informed consent, diagnosis-to-treatment delay in colorectal cancer,
and antibiotic prophylaxis show room for improvement in the pilot-tested
hospital.
PMID- 27499299
TI - Factors Influencing Consumption of Fruits and Vegetables in Older Adults in New
Orleans, Louisiana.
AB - BACKGROUND: OBJECTIVES: The objective of this study was to identify demographic,
social and structural factors associated with intake of fruit and vegetables in
older adults in New Orleans, Louisiana. DESIGN: A cross-sectional randomly
sampled, address-based telephone survey of households in Orleans Parish,
Louisiana was conducted with the household's main grocery shopper. SETTING: All
participants were in the New Orleans metro area and were surveyed in 2011.
PARTICIPANTS: Participants were 2,834 residents identified as the households'
main grocery shopper in Orleans Parish, Louisiana. Participants were primarily
female (75%), African-American (53%), approximately 10 percent of the sample
reported receipt of government assistance. Approximately 37% of the sample was
age 65 and older. MEASUREMENTS: Measures included a telephone administered survey
assessing demographic characteristics, food intake, access to supermarkets and
other food sources, transportation, self-reported health, and frequency of
grocery shopping. RESULTS: Older adults consumed fewer fresh fruits and
vegetables (FV) than younger adults (p<0.01). Bivariate associations with
decreased FV included older age, receipt of government assistance, African
American race, use of mobility aid, and poorer health. Multivariate factors
associated with lower consumption include age, African American race, and poorer
self-reported health. Women reported more fruit and vegetable consumption than
men. CONCLUSIONS: FV consumption is associated with improved health and reduced
mortality. Older adults are less likely to consume fruits and vegetables,
therefore addressing reduced FV consumption in older adults is a potential target
for improving health outcomes in older adults. Specifically targeting African
Americans and those with poorer health, as well as males may be an important
focus for interventions.
PMID- 27499300
TI - Identifying Low Muscle Mass in Patients with Hip Fracture: Validation of
Biolectrical Impedance Analysis and Anthropometry Compared to Dual Energy X-ray
Absorptiometry.
AB - BACKGROUND: Older hip fracture patients often have reduced muscle mass, which is
associated with adverse outcomes. Dual energy X-ray absorptiometry (DXA) can
determine muscle mass, but is not practical in the acute phase. We investigated
bioelectrical impedance analysis (BIA) and anthropometry compared against DXA for
detecting low muscle mass in hip fracture patients. METHODS: This was a cross
sectional validation study at two Norwegian hospitals on 162 hip fracture
patients aged >= 65 years. Appendicular lean mass (ALM) was determined by DXA,
BIA and anthropometry 3 months after hip fracture. ALM by BIA was calculated by
the Kyle, Janssen, Tengvall and Sergi equations, and ALM by anthropometry by the
Heymsfield and Villani equations. The area under the receiver operating
characteristic curve (AUC) was used to compare BIA and anthropometry for
determining low ALM (<=5.67 kg/m2 for women and <=7.25kg/m2 for men). RESULTS:
Mean age was 79 years (SD 7.9), 74% were female. Mean ALM by DXA was 14.8 kg (SD
2.3) for women and 20.8 kg (SD 4.2) for men and 45% of women and 60% of men had
low ALM. BIA (Kyle) in women (AUC 0.81, 95% confidence interval 0.72-0.89) and
BIA (Sergi) in men (AUC 0.89, 95% CI 0.80-0.98) were best able to discriminate
between low and normal ALM. Anthropometry (Heymsfield) was less accurate than BIA
in women (AUC 0.64, 95% CI 0.54-0.75), and equal to BIA in men (AUC 0.72, 95% CI
0.72 0.56-0.87). CONCLUSION: BIA (Sergi, Kyle and Tengvall) and anthropometry
(Heymsfield) can identify low muscle mass in hip fracture patients.
PMID- 27499301
TI - Association of Dietary Variety with Body Composition and Physical Function in
Community-dwelling Elderly Japanese.
AB - OBJECTIVES: To examine the associations of dietary variety with body composition
and physical function in community-dwelling elderly Japanese. DESIGN: Cross
sectional study. SETTING: Community-based. PARTICIPANTS: A total of 1184
community-dwelling elderly adults aged 65 and over. MEASUREMENTS: Dietary variety
was assessed with a food frequency questionnaire (maximum, 10 points) that
encompassed the 10 main food components of Japanese meals (meat, fish/shellfish,
eggs, milk, soybean products, green/yellow vegetables, potatoes, fruit, seaweed,
and fats/oils). Body composition was determined by multifrequency bioelectrical
impedance analysis. Physical function was assessed by measuring grip strength and
usual walking speed. Multiple linear regression analysis was used to examine the
associations of dietary variety with body composition and physical function.
RESULTS: After adjusting for potential confounders, higher dietary variety scores
were independently associated with higher lean mass (beta (SE): 0.176 (0.049),
p<0.001) and appendicular lean mass (beta (SE): 0.114 (0.027), p<0.001) but not
with body fat mass. Elders with a higher dietary variety score had greater grip
strength and faster usual walking speed (beta (SE): 0.204 (0.071), p=0.004, and
beta (SE): 0.008 (0.003), p=0.012, respectively). CONCLUSION: Greater dietary
variety was significantly associated with greater lean mass and better physical
function in Japanese elders. The causal relationship warrants investigation in a
prospective study.
PMID- 27499302
TI - Swallowing Function and Nutritional Status in Japanese Elderly People Receiving
Home-care Services: A 1-year Longitudinal Study.
AB - OBJECTIVES: Malnutrition is a serious health concern for frail elderly people.
Poor oral function leading to insufficient food intake can contribute to the
development of malnutrition. In the present study, we explored the longitudinal
association of malnutrition with oral function, including oral health status and
swallowing function, in elderly people receiving home nursing care. DESIGN:
Prospective observational cohort study with 1-year follow-up. SETTING: Two mid
sized cities in Fukuoka, Japan from November 2010 to March 2012. PARTICIPANTS:
One hundred and ninety-seven individuals, aged >= 60 years, living at home and
receiving home-care services because of physical disabilities, without
malnutrition. MEASUREMENTS: Oral health status, swallowing function, taking
modified-texture diets such as minced or pureed foods, nutritional status,
cognitive function, and activities of daily living were assessed at baseline. The
associations between malnutrition at 1-year follow-up and these related factors
were analyzed using a logistic regression model. RESULTS: Swallowing disorders
[risk ratio (RR): 5.21, 95% confidence interval (95% CI): 1.65-16.43] were
associated with malnutrition. On the other hand, oral health status did not have
a direct association with malnutrition. CONCLUSION: Swallowing disorders may be
associated with the incidence of malnutrition in elderly people receiving home
care. The findings indicate that maintaining swallowing function may contribute
to the prevention of malnutrition in frail elderly people.
PMID- 27499303
TI - Malnutrition in Very Old Hospitalized Patients: A New Etiologic Factor of Anemia?
AB - BACKGROUND: Anemia and malnutrition are highly prevalent, frequently concomitant
and associated with negative outcomes and mortality in the elderly. OBJECTIVES:
To evaluate the association between these two entities, and test the hypothesis
that protein-energy deficit could be etiology of anemia. DESIGN: Prospective case
control study. SETTING: Geriatric and Rehabilitation Hospital, Geneva University
Hospitals, Switzerland. PARTICIPANTS: 392 patients (mean age 84.8 years old,
68.6% female). MAIN OUTCOME MEASURES: Hematological (hemoglobin (Hb)), chemical
(iron work up, cyanocobalamin, folates, renal function, C-Reactive Protein (CRP))
and nutrition (albumin, prealbumin) parameters, and mini nutritional assessment
short form (MNA-SF). RESULTS: The prevalence of anemia (defined as Hb<120 g/l)
was 39.3%. Anemic patients were more frequently malnourished or at risk of
malnutrition according to the MNA-SF (p=0.047), with lower serum albumin (p
<0.001) and prealbumin (p <0.001) levels. Thirty-eight percent of these patients
had multiple causes and 14.3% had no cause found for anemia. Among the latter
90.9% of patients with unexplained anemia had albumin levels lower than 35g/l.
After exclusion of iron,vitamin B12 and folic acid deficits, anemic patients had
lower albumin (p<0.001) and prealbumin (p 0.007) levels. Albumin level explained
84.5% of the variance in anemia. In multivariate analysis albumin levels remain
associated with Hb only in anemic patients, explaining 6.4% of Hb variance (adj
R2) and 14.7% (adj R2) after excluding inflammatory parameters (CRP>10).
CONCLUSIONS: Albumin levels are strongly associated with anemia in the elderly.
Screening for undernutrition should be included in anemia assessment in those
patients. Further prospective studies are warranted in order to explore the
effect of protein and energy supplementation on hemoglobin level.
PMID- 27499304
TI - Should Sensory Impairment Be Considered in Frailty Assessment? A Study in the
GAZEL Cohort.
AB - OBJECTIVES: The assessment of sensory difficulties is sometimes included in the
screening of frailty in ageing population. This study aimed to compare the
prevalence of frailty and associated risk of adverse outcomes depending on
whether sensory difficulties participated in the definition of frailty. DESIGN:
Prospective cohort study - GAZEL cohort. SETTING: France. PARTICIPANTS: The
13,128 subjects who completed a questionnaire in 2012. MEASUREMENTS: According to
the Strawbridge questionnaire, subjects were considered frail if they reported
difficulties in two domains or more among physical, nutritive, cognitive and
sensory domains. The risk of adverse health outcomes was assessed by using
logistic regression models (hospitalisations, onset of difficulty in performing
movements of everyday life) and multivariate Cox proportional hazards models
(mortality). RESULTS: Mean age was 66.8 +/- 3.4 years and 73.8% were males. The
prevalence of frailty varied from 4.4 to 14.2% depending on whether the sensory
domain was excluded or included. During follow-up, 182 deaths (1.4%), 479
hospitalisations (3.6%) and 703 cases of new disability (8.0%) were observed.
Both definitions of frailty predicted the onset of difficulties to perform
everyday movements, with 2 to 3-fold increase in the risk. The inclusion of the
sensory domain in the definition made frailty predictive of hospitalisations
(Odds Ratio 1.31 [1.01-1.70]) but the association with mortality was only
observed when sensory difficulties were ignored (Hazard Ratio 2.28 [1.32-3.92]).
CONCLUSION: The inclusion of a sensory domain into a frailty screening instrument
has a major impact in terms of prevalence and modifies the risk profile
associated with frailty. In order to develop the use of frailty screening
instruments in clinical practice, further researches will need to carefully
evaluate the impact on risk prediction of the different domains involved.
PMID- 27499305
TI - Characterizing Magnitude and Selectivity of Attrition in a Study of Mild
Cognitive Impairment.
AB - OBJECTIVES: Attrition is one of the greatest difficulties in longitudinal studies
on cognitive ageing because of the associated risk of underestimating declines.
The aims of this paper were to characterize the magnitude and selectivity of
attrition in a study of mild cognitive impairment. DESIGN: Forty two patients
with multiple-domain amnestic MCI, 71 with single-domain amnestic MCI, 35 with
non-amnestic MCI and 318 healthy controls were recruited from primary care
centers and assessed at baseline. MEASUREMENTS: All participants underwent
extensive neuropsychological evaluation, including the Mini-Mental State
Examination, the Californian Verbal Learning Test, the CAMCOG-R battery, the
Counting Span task and Listening Span task, and the Subjective Memory Complaints
Questionnaire. RESULTS: 21.5% of the participants at baseline did not participate
in the follow-up assessment. Comparison between respondents and non-returners did
not reveal differences in cognitive performance in the MCI group. Data obtained
at the initial assessment regarding comorbidity, social activities and attention
given to memory training enabled prediction of the status of the participants in
the follow-up assessment. CONCLUSION: Identification of potential non- returners
is relevant, especially in MCI studies, in order to develop retention strategies
to minimize attrition.
PMID- 27499307
TI - Editorial: What Is New in Exercise Regimes for Frail Older People - How Does the
Erasmus Vivifrail Project Take Us Forward?
PMID- 27499306
TI - Impact of Cognitive Frailty on Daily Activities in Older Persons.
AB - OBJECTIVES: To identify the relationships between physical and/or cognitive
frailty and instrumental activities of daily living (IADL) functioning in
community living older persons. DESIGN: Cross sectional observation study.
SETTING: Data extracted from the 2011-2013 of the National Center for Geriatrics
and Gerontology-Study of Geriatric Syndromes (NCGG-SGS) database. PARTICIPANTS: A
total of 8,864 older adults aged >= 65 years who were enrolled in the NCGG-SGS.
MEASUREMENTS: We characterized physical frailty as limitations in three or more
of the following five domains: slow walking speed, muscle weakness, exhaustion,
low activity and weight loss. To screen for cognitive impairment, we used the
National Center for Geriatrics and Gerontology-Functional Assessment Tool (NCGG
FAT) which included tests of word list memory, attention and executive function
(tablet version of the Trail Making Test, part A and B), and processing speed
(tablet version of the Digit Symbol Substitution Test). Two or more cognitive
impairments indicated by an age-adjusted score of at least 1.5 standard
deviations below the reference threshold was characterized as cognitive
impairment. Each participant reported on their IADL status (use of public
transportation, shopping, management of finances, and housekeeping) and several
potential confounders such as demographic characteristics. RESULTS: The overall
prevalence of physical frailty, cognitive impairment, and cognitive frailty, i.e.
co-occurrence of frailty and cognitive impairment, was 7.2%, 5.2%, and 1.2%,
respectively. We found significant relationships between IADL limitations and
physical frailty (Odds Ratio (OR) 1.24, 95% confidence interval (95% CI) 1.01 to
1.52), cognitive impairment (OR 1.71, 95% CI 1.39 to 2.11), and cognitive frailty
(OR 2.63, 95% CI 1.74 to 3.97). CONCLUSION: Using the NCGG-SGS frailty criteria,
we found more participants with physical frailty than with cognitive frailty. The
individuals with cognitive frailty had the highest risks of IADL limitations.
Future investigation is necessary to determine whether this population is at
increased risk for incidence of disability or mortality.
PMID- 27499308
TI - Physical Activity and Early Rehabilitation in Hospitalized Elderly Medical
Patients: Systematic Review of Randomized Clinical Trials.
AB - BACKGROUND: To critically review the effect of interventions incorporating
exercise and early rehabilitation (physical therapy, occupational therapy, and
physical activity) in the functional outcomes (i.e., active daily living tests,
such as Barthel Index Scores, Timed-up-and go, mobility tests), and feasibility
in hospitalized elderly medical patients. DESIGN: Systematic review of the
literature. METHODS: A literature search was conducted using the following
databases and medical resources from 1966 to January 2014: PubMed (Medline),
PEDro, the Cochrane Central Register of Controlled Trials and the Cochrane
Database of Systematic Reviews, Google Scholar, ClinicalTrials.gov, Clinical
Evidence, SportsDiscus, EMBASE and UptoDate. Studies must have mentioned the
effects of early rehabilitation on the above mentioned functional outcomes and
feasibility. Data on the mortality, economic profile and average stay were also
described. RESULTS: From the 6564 manuscripts potentially related to exercise
performance in hospitalized elderly patients, the review focused on 1086, and 17
articles were ultimately included. Regarding functional outcomes after discharge,
four studies observed significant improvement in functional outcomes following
early rehabilitation, even up to twelve months after discharge. Eight studies
directly or indirectly assessed the economic impact of exercise intervention.
Five of them did not show any increase in costs, while three concluded that the
intervention was cost effective. No adverse effect related with the interventions
were mentioned. CONCLUSION: The introduction of an exercise program for
hospitalized elderly patients may be feasible, and may not increase costs.
Importantly, early rehabilitation may also improve the functional and healthcare.
PMID- 27499309
TI - Accelerometer Assessment of Physical Activity and Its Association with Physical
Function in Older Adults Residing at Assisted Care Facilities.
AB - OBJECTIVES: To describe levels of physical activity among older adults residing
at assisted care facilities and their association with physical function. DESIGN:
Cross-sectional analysis. SETTING: Assisted care facilities within the greater
Boston, MA area. PARTICIPANTS: Older adults aged 65 years and older (N = 65).
MEASUREMENTS: Physical Activity Level (PAL) as defined by quartiles from
accelerometry (counts and steps), Short Physical Performance Battery (SPPB)
Score, gait speed, and handgrip strength. RESULTS: Participants in the most
active accelerometry quartile engaged in 25 minutes/week of moderate to vigorous
physical activity (MVPA) and walked 2,150 steps/day. These individuals had an
SPPB score, 400 meter walk speed, and handgrip strength that was 3.7-3.9 points,
0.3-0.4 meters/second, and 4.5-5.1 kg greater respectively, than individuals in
the lowest activity quartile, who engaged in less than 5 min/wk of MVPA or took
fewer than 460 steps/day. CONCLUSION: Despite engaging in physical activity
levels far below current recommendations (150 min/week of MVPA or > 7000
steps/day), the most active older adults in this study exhibited clinically
significant differences in physical function relative to their less active peers.
While the direction of causality cannot be determined from this cross-sectional
study, these findings suggest a strong association between PAL and physical
function among older adults residing in an assisted care facility.
PMID- 27499310
TI - A comparison of Frailty Indexes Based on a Comprehensive Geriatric Assessment for
the Prediction of Adverse Outcomes.
AB - OBJECTIVE: To compare the ability of different frailty indexes based on a
standardized comprehensive geriatric assessment (FI-CGAs) for predicting adverse
outcomes. DESIGN AND SETTING: Prospective cohort study. Geriatric wards of a
general hospital. PARTICIPANTS: 307 hospitalized patients >= 65 years.
MEASUREMENTS: The FI-CGA-10D (potential health deficits in ten functional
domains), the FI-CGA-10D+CM (aforementioned potential health deficits and co
morbidity burden) and the FI-CGA-MIHD (multiple, individual potential health
deficits, including functional deficits, co-morbid diseases, amongst others) were
assessed at baseline during the patients' hospital stay. The FI-CGAs were
analyzed as categorical (according to a FI-CGA score < and >= 0.25) and
continuous variables. Patients were followed up over 6 months. RESULTS: The FI
CGA-10D, FI-CGA-10+CM and the FI-CGA-MIHD predicted 6-month mortality when
expressed as categorical (area under the receiver operating characteristic curve
(AUC): AUC = 0.611, AUC = 0.637, AUC = 0.616, all p < 0.050, respectively) or
continuous variables (AUC = 0.769, AUC = 0.837, AUC = 0.834, all p < 0.001,
respectively). AUC comparisons showed that all three FI-CGAs exhibited a
comparable ability to predict 6-month mortality when the FI-CGAs were expressed
as categorical variables (all p > 0.200) and the FI-CGA-10D+CM and the FI-CGA
MIHD showed a better ability to predict 6-month mortality than the FI-CGA-10D,
when the FI-CGAs were expressed as continuous variables (p < 0.001 and p = 0.007,
respectively). None of the FI-CGAs predicted any of the other outcomes, i.e.,
unplanned re-admission to hospital and a fall during follow-up, irrespective of
whether the FI-CGAs were expressed as categorical or continuous variables (all p
>= 0.050). CONCLUSIONS: The more complex FI-CGAs, i.e., the FI-CGA-10D+CM and the
FI-CGA-MIHD, revealed better ability to predict 6 month mortality than the more
simple FI-CGA, i.e., the FI-CGA-10D.
PMID- 27499311
TI - The Randomized Control Trial of the Effects of Testosterone and a Nutritional
Supplement On Hospital Admissions in Undernourished, Community Dwelling, Older
People.
AB - OBJECTIVE: In a pilot single centre study we found that treatment of
undernourished older, community dwelling people for one year with oral
testosterone (placebo-controlled) and a nutritional supplement (no control) was
associated with a significant reduction in hospitalizations. A larger,
multicentre study was conducted to investigate further this potentially important
finding. DESIGN: One year, randomized, placebo-controlled, multi-centre, double
blind, trial. SETTING: Community. PARTICIPANTS: 53 undernourished men and women
aged 65 years and older. INTERVENTION: Oral testosterone undecanoate (40 mg/day
women, 160 mg/day men) and high energy oral nutritional supplement (2108-2416
kJ/day) or placebo medication and low energy (142-191 kJ/day) "placebo" oral
nutritional supplementation. MEASUREMENTS: Hospital admissions, falls and other
variables were assessed. RESULTS: 53 subjects were recruited (64% male and mean
age 77 years), which was substantially less than planned. Sixteen subjects (30%)
were admitted to hospital at least once, with a total of 29 admissions. Eight
subjects (32%) in the placebo arm were admitted to hospital, whilst in the
intervention group also there were eight (29%) subjects admitted to hospital
during the study period. There was no difference in the number of
hospitalisations (P = 0.842), length of hospitalization (P=0.645) or quality of
life [mental health P=0.195 and physical health P=0.451) between the treatment
arms. CONCLUSIONS: In undernourished older people, treatment with testosterone
and a nutritional supplementation did not reduce the number and length of
hospitalisations or improve quality of life.
PMID- 27499313
TI - Identification and Quantitation of the Lipation Product 2-Amino-6-(3
methylpyridin-1-ium-1-yl)hexanoic Acid (MP-Lysine) in Peanuts.
AB - The lipid peroxidation product acrolein was semiquantitated by GC-MS (EI) in
unheated and heated peanut oil, respectively, representing a model system for
peanut roasting. Depending on the heating time, acrolein levels significantly
increased from 0.2 to 10.7 mg/kg oil. As a result of heating N(alpha)-acetyl-l
lysine and acrolein, the pyridinium derivative 2-acetamido-6-(3-methylpyridin-1
ium-1-yl)hexanoic acid (MP-acetyl lysine) was identified. In addition, the lysine
derivative 2-amino-6-[5-(hydroxymethyl)-3,6-dihydro-2H-pyridin-1-yl]hexanoic acid
was identified after reduction and hydrolysis. After preparation of 2-amino-6-(3
methylpyridin-1-ium-1-yl)hexanoic acid (MP-lysine) as reference material, its
amounts were quantitated in acrolein-modified peanut proteins by HPLC-ESI-MS/MS
after acid hydrolysis, showing that at low acrolein concentrations, the
modification of lysine could be entirely explained by the formation of MP-lysine.
Furthermore, for the first time, MP-lysine was quantitated in peanut samples in
amounts up to 10.2 mg/kg, showing an increase depending on the roasting time.
Thus, MP-lysine might represent a marker to evaluate the extent of food protein
lipation by acrolein.
PMID- 27499312
TI - Sarcopenic Obesity: An Appraisal of the Current Status of Knowledge and
Management in Elderly People.
AB - Today's increased life expectancy highlights both age-related changes in body
composition and a higher prevalence of obesity. Sarcopenic obesity (SO) is
assuming a prominent role in cardio-metabolic risk because of the double
metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity
(obesity). This review evaluates the related studies that have been published
over the past 10 years in order to give an updated overview of this new syndrome.
There is no consensus on the definition of SO due to the wide heterogeneity of
diagnostic criteria and choice of body composition components needed to assess
this phenotype. There is a growing body of evidence that the ethio-pathogenesis
of SO is complex and multi-factorial, as the consequences are a combination of
the outcomes of both sarcopenia and obesity, where the effects are maximised. In
order to manage SO, it is important to make lifestyle changes that incorporate
weight loss, physical exercise and protein supplementation.
PMID- 27499314
TI - An integrin alphavbeta3 antagonistic modified peptide inhibits tumor growth
through inhibition of the ERK and AKT signaling pathways.
AB - HM-3, an RGD (Arg-Gly-Asp)-modified antitumor polypeptide designed independently,
has been demonstrated for its robust inhibitory effects on tumors. However, the
intravenous administration and short half-life in vivo are inconvenient to its
clinical application. To solve these issues, PEGylated HM-3 (mPEG-SC20k-HM-3)
with prolonged half-time in vivo and subcutaneous administration was obtained
after repeated screening of different types of PEG and numerous efficacy assays.
The present study aimed to evaluate the antitumor activity and investigate the
mechanism of the modified peptide to interpret the antitumor properties of mPEG
SC20k-HM-3 comprehensively and clearly. The results of the antitumor activity
assays in vitro indicated that mPEG-SC20k-HM-3 exhibited a marked inhibitory
activity on tumor metastasis and angiogenesis. mPEG-SC20k-HM-3 (73.4 mg/kg, sc)
achieved a tumor inhibitory rate of 70.1% in an H460 (human non-small cell lung
cancer) xenograft model with scarce cytotoxicity, compared with a rate of 72.2%
for Avastin (10.0 mg/kg, iv). The mechanistic study showed that mPEG-SC20k-HM-3
could target integrin alphavbeta3 to block the downstream ERK and Akt pathways,
as the expression levels of VEGF, Akt1, p-Akt1, ERK1/2, p-ERK1/2, MEK1, p-MEK1,
integrin alphav and beta3 were reduced after HUVECs were incubated with mPEG
SC20k-HM-3 for 24 h. In conclusion, the antitumor activity of mPEG-SC20k-HM-3 in
vitro and in vivo is promising and the mechanism was clearly reflected in the
present study.
PMID- 27499315
TI - Are all case reports worth publishing?
PMID- 27499316
TI - Is there crosstalk between subchondral bone, cartilage, and meniscus in the
pathogenesis of osteoarthritis?
AB - OBJECTIVES: This study aims to investigate if there is any crosstalk between
subchondral bone, cartilage, and meniscus in the pathogenesis of osteoarthritis.
PATIENTS AND METHODS: Twelve female patients (mean age 64 years; range 59 to 71
years) with osteoarthritis in medial compartment were included in the study. The
samples of subchondral bone, cartilage and meniscus were obtained during total
knee arthroplasty. Degenerated tissue samples obtained from medial compartment
were used as the experimental group (12 samples of subchondral bone and
cartilage, 1x1 cm each; and 12 samples of meniscus, 1x1 cm each). Healthy tissue
samples obtained from lateral compartment were used as the control group (12
samples of subchondral bone and cartilage; 1x1 cm each; and 12 samples of
meniscus, 1x1 cm each). After decalcification, tissue samples were evaluated with
light and transmission electron microscopy. RESULTS: In the experimental group,
light microscopic evaluation of subchondral bone samples demonstrated that the
cartilage-to-bone transition region had an irregular structure. Degenerated
cartilage cells were observed in the transition region and bone cells were
significantly corrupted. In the experimental group, light microscopic evaluation
of the meniscus samples demonstrated that the intercellular tissue was partly
corrupted. Separation and concentration of the collagen fibers were evident. All
findings were supported with ultra structural evaluations. CONCLUSION: Our
findings indicate that degeneration of subchondral bone, cartilage, and meniscus
probably plays a role in the pathogenesis of osteoarthritis with crosstalk.
PMID- 27499317
TI - Is axial shape of distal femur different in normal and osteoarthritic female
patients?
AB - OBJECTIVES: This study aims to investigate whether the axial shape of the distal
femur is different between normal and osteoarthritic female knees using
statistical shape analysis. PATIENTS AND METHODS: A total of 126 knee magnetic
resonance images of 126 female patients were examined in this study conducted
between May 2013 and May 2014. Patients were divided into two groups as study and
control groups. The study group consisted of 41 patients (median age 65 years;
min. 36 - max. 88 years) who were determined to have knee osteoarthritis, while
the control group consisted of 85 patients (median age 43 years; min. 20 - max.
81 years) without knee osteoarthritis. Anatomic and constructive landmarks were
selected and marked on each two-dimensional digital image in the axial section of
the distal femur. The mean axial shapes of the distal femur were compared between
the groups by statistical shape analysis. Shape deformations were investigated by
thin plate spline analysis. RESULTS: There were significant differences between
the groups regarding the axial shape of the distal femur. Maximal deformation was
observed in the femoral notch area. CONCLUSION: This study showed that there are
deformations in the axial shape of the distal femur in female patients with knee
osteoarthritis. Further studies are required to determine whether these
differences are important for implant design and surgical technique of total knee
replacement.
PMID- 27499318
TI - Comparison of the clinical and radiological outcomes of open reduction via medial
and anterior approach in devleopmental dysplasia of the hip.
AB - OBJECTIVES: This study aims to investigate the effects of surgical approach on
the clinical and radiological outcomes, the incidence of avascular necrosis
(AVN), and the need for revision surgery in children undergoing open reduction
via medial or anterior approach for developmental dysplasia of the hip (DDH).
PATIENTS AND METHODS: Forty-three hips of 36 patients (9 males, 27 females; mean
age 13.8 month; range 6 to 18 months) treated for DDH, followed-up regularly for
at least four years between January 1997 and December 2010, and who were aged
five or above in the final control were included in this retrospective study.
Patients were divided into two groups according to surgical approaches. Group 1
consisted of 21 hips of 19 patients who underwent open reduction through medial
approach. Group 2 consisted of 22 hips of 17 patients who underwent open
reduction through anterior approach. Groups were compared in terms of clinical
and radiological outcomes as well as the incidence of AVN and the need for
revision surgery. RESULTS: There was no statistically significant difference
between the groups with respect to clinical and radiological outcomes (p=0.407
and p=0.661, respectively). Similarly, there was no statistically significant
difference between the groups in terms of AVN incidence and need for revision
surgery (p=0.993 and p=0.170, respectively). On the other hand, acetabular index
improved significantly in both groups at follow-up. CONCLUSION: This study showed
that open reduction via medial or anterior approach in DDH has similar clinical
and radiological results, significant improvement was achieved in the acetabular
index with both approaches, and no significant difference was present in the
incidence of AVN and the need for revision surgery between the groups.
PMID- 27499319
TI - [Early-term hip development following Pemberton osteotomy: a radiological follow
up].
AB - OBJECTIVES: This study aims to evaluate the relationship of early-term
radiological changes with development of the hip joint after Pemberton osteotomy.
PATIENTS AND METHODS: This study, which was conducted between January 2010 and
December 2014, included 101 hips (26 bilateral) of 75 patients (25 males, 50
females; mean age 31.5 months; range 15 to 71 months) which were performed
Pemberton osteotomy due to developmental dysplasia of the hip. Radiologically, we
assessed the parameters of center-edge angle, acetabular index (AI), and
acetabular depth index (ADI). We measured the surface area of the femoral head
ossific nucleus on anterior-posterior pelvic X-rays. We graded the degree of hip
dislocation according to Tonnis classification while the femoral head avascular
necrosis was graded according to Kalamchi-MacEwen classification. We separated
the operated hips in all patients and in only unilaterally operated patients in
three groups according to their follow-up durations as 12 months, 12 to 24
months, and more than 24 months. We analyzed the associations of radiological
parameters in all follow-up durations. RESULTS: Mean follow-up duration was 22.5
months (range, 6 to 66 months). Preoperative mean AI was 42.25 degrees (range,
29 degrees to 60 degrees ) and last follow-up mean AI was 20.45 degrees (range,
10 degrees to 32 degrees ). Preoperative mean ADI was 16.48 degrees (range, 9
degrees -30 degrees ) and last follow-up mean ADI was 26.1 degrees (range, 23
degrees -47 degrees ). Sixty hips were Tonnis type 4, 26 hips were type 3, and 15
hips were type 2. According to follow-up duration classification; there were 32
hips (21 unilateral) with 12 month-follow-up, 43 hips (17 unilateral) with 12-24
month-follow-up, and 26 hips (11 unilateral) with more than 24-month follow-up.
We applied shortening osteotomy to 18 femurs. According to Kalamchi-MacEwen
classification; avascular necrosis type 1 was present in 16 hips, type 2 in two
hips, type 3 in three hips, and type 4 in two hips. We performed revision
operations for five hips because of recurrent subluxations. CONCLUSION: We
observed progressive improvements in hip joints and consequently in radiological
parameters in the early-term after Pemberton osteotomy.
PMID- 27499320
TI - Effect of ulnar styloid fracture on outcomes after conservative treatment of
distal radius fracture.
AB - OBJECTIVES: This study aims to investigate the effect of accompanying ulnar
styloid fracture (USF) on clinical outcomes and hand-wrist muscle strength in
conservatively treated active patients after displaced distal radius fracture
(DRF). PATIENTS AND METHODS: The retrospective study, which was conducted
November 2012 and September 2016, included 56 patients (34 males, 22 females;
mean age 28.8 years; range 20 to 40 years) with displaced DRF treated with closed
reduction and casting. Patients were divided into three groups according to ulnar
styloid status as group A (intact ulnar styloid), group B (USF non-union), and
group C (healed USF). Grip strength, quick-disabilities of the arm, shoulder and
hand (DASH) score, and joint range of motions were evaluated; the results were
combined with measurements of isokinetic muscle strengths of hand-wrist region.
Magnetic resonance imaging was performed to evaluate the accompaniment of distal
radioulnar joint injury and triangular fibrocartilage complex (TFCC) lesion.
RESULTS: There were no significant differences between the groups regarding joint
range of motion, grip strength, and quick-DASH scores. However, the peak torque
and total work of supination was better in group A compared to group B (p=0.008
and p=0.006, respectively). According to the magnetic resonance imaging findings,
of the 10 patients with detected TFCC lesion, four were in group C, five in group
B, and one was in group A. CONCLUSION: Results of this study suggest that USF
should not be the focus of attention during initial treatment of DRF and surgical
intervention might be considered in case of an accompanying TFCC lesion.
PMID- 27499321
TI - Primary malignant fibrous histiocytoma of long bones: long-term follow-up.
AB - OBJECTIVES: This study aims to evaluate patients diagnosed with malignant fibrous
histiocytoma and investigate the possible prognostic factors associated with
duration of survival. PATIENTS AND METHODS: The study, which was conducted
between May 1994 and September 2013, included 14 patients diagnosed as malignant
fibrous histiocytoma (12 males, 2 females; median age 48 years; range 17 to 64
years). We evaluated patients' demographic features, location of the pathology,
histological findings, surgical margins, and treatment modalities and
investigated the effects of these parameters on survival. RESULTS: Femur was the
most frequently involved bone, followed by tibia and humerus. The median follow
up duration of the patients was 129 months. We performed limb salvage surgeries
in 13 patients and amputation in one patient. Surgical margins were marginal in
three patients and postoperative radiotherapy was performed for local control of
the disease. Although there was no local recurrence in these patients, distant
metastasis developed in two patients, indicating the importance of surgical
margin as a significant factor on survival. Five-year survival rate was 81.9% in
patients with wide surgical margins and 33.3% in patients with marginal margins.
CONCLUSION: Surgical excision with wide margins and adjuvant chemotherapy
provided adequate control of the disease and longer survival. The only prognostic
factor statistically significantly associated with duration of survival was
surgical margins. Neoadjuvant chemotherapy may be used when there is a suspicion
of not obtaining adequately wide surgical margin perioperatively due to close
association with neurovascular structures.
PMID- 27499322
TI - Less invasive surgery using external fixator for the treatment of subtrochanteric
femur fracture in a high-risk geriatric patient.
AB - A 90-year-old female patient was admitted to our clinic complaining of pain in
her left hip which occurred due to fall from a chair. Her medical history
included memory loss and mental changes associated with Alzheimer's disease and
depression. Patient's cooperation and orientation were weak. Range of motion of
the left hip was restricted and painful. Radiographs of the left hip demonstrated
subtrochanteric comminuted fracture of femur. Laboratory tests revealed anemia
and liver insufficiency. Departments of internal medicine and anesthesiology
reported high risk for surgery. Surgery was performed under spinal anesthesia on
radiolucent table and in supine position. Using fluoroscopy, subtrochanteric
comminuted fracture of femur was reduced. Proximally, two Schanz screws were
placed through femoral neck and head in axial plane, and distally, three Schanz
screws were placed through femoral shaft in coronal plane. Finally, fixation of
the screws was achieved with an external fixator which was made of carbon fiber
rods. Patient was allowed to sit in the bed and move around with a wheelchair as
of the day of surgery. No infection or loosening of fixator occurred.
PMID- 27499323
TI - Painful, pediatric sacral aneurysmal bone cyst treated by curettage and fresh
frozen allograft.
AB - In this article, we report a rarely localized sacral aneurysmal bone cyst (ABC)
successfully treated by curettage and bone grafting with fresh frozen fibular
allograft (FFA) in a 14-year-old girl patient. The cyst was at S1-2 level and
treated with aggressive curettage and bone grafting with two FFAs. All complaints
of the patient resolved at the 24th month of treatment and bony union of the
cystic cavity was observed radiologically. Curettage and FFA may be safely used
for filling the cavity in the treatment of sacral ABC in pediatric age to provide
a structural and biological reinforcement.
PMID- 27499324
TI - Malignant transformation of aggressive osteoblastoma to ostesarcoma.
AB - Osteoblastoma is a rare, bone-forming tumor, characterized by osteoid and woven
bone production. A 13-year-old boy patient presented to our clinic with complaint
of pain in his left proximal tibia. We performed curettage and bone grafting for
the lesion diagnosed as osteoblastoma. Two years later, the patient admitted to
the hospital with a mass in the same region which was diagnosed by biopsy to be
osteosarcoma. Patient was performed reconstruction operation with local resection
and mega prosthesis. Fourteen months after termination of chemotherapy, lung
metastasis developed and the patient died consequently. In this article, we
reported a patient with aggressive osteoblastoma of the left proximal tibia which
recurred as an osteosarcoma and discussed the difficulties in the
histopathological diagnosis and management of these patients. As some other cases
in the literature, our case indicates that osteoblastomas may undergo malignant
transformation.
PMID- 27499325
TI - Open Galeazzi fracture with ipsilateral elbow dislocation.
AB - Combination of the Galeazzi fracture and dislocation of the elbow joint in same
extremity is very rare. In this article, we report a 26-year-old male patient
with a posterolateral dislocation of the elbow and ipsilateral volar type
Galeazzi fracture. We performed closed reduction for the elbow dislocation during
admission to the emergency department. Patient was taken to the operating room in
the sixth hour of his application to emergency department and open wound on the
ulnovolar region of the wrist was closed primarily after irrigation and
debridement. We performed open reduction and internal fixation of the radial
fracture with a dynamic compression plate. After fixation, we evaluated the
stability of the elbow joint and distal radioulnar joint. Distal radioulnar joint
was unstable under fluoroscopic examination and fixed with one 1.8 mm Kirschner
wire in a pronated position. Then, elbow joint was stable. One year after
surgery, patient had no pain or sings of instability. At the last follow-up,
range of motion of the elbow was 10 degrees -135 degrees and forearm pronation
and supination were 70 degrees .
PMID- 27499326
TI - Above-knee amputation followed by femoral replantation: 21-year follow-up results
after lower limb replantation.
AB - In this article, we report successful treatment of serious complications of
replantation after traumatic mid-third femoral amputation. To the best of our
knowledge, no similar case has been reported in the literature. A 38-year-old
healthy male sustained a mid-third right traumatic femoral amputation. We
performed replantation. Oliguria and anuria occurred and were treated
successfully with hemofiltration and hemodialysis. Six years later, patient
walked wearing orthopedic shoes and also protective sensibility recovered on the
limb. Serious complications of proximal lower limb replantation can be treated
successfully and the limb can be saved.
PMID- 27499328
TI - Molecular and structural basis of low interfacial energy of complex coacervates
in water.
AB - Complex coacervate refers to a phase-separated fluid, typically of two oppositely
charged polyelectrolytes in solution, representing a complex fluid system that
has been shown to be of essential interest to biological systems, as well as for
soft materials processing owing to the expectation of superior underwater coating
or adhesion properties. The significance and interest in complex coacervate
fluids critically rely on its low interfacial tension with respect to water that,
in turn, facilitates the wetting of macromolecular or material surfaces under
aqueous conditions, provided there is attractive interaction between the
polyelectrolyte constituents and the surface. However, the molecular and
structural bases of these properties remain unclear. Recent studies propose that
the formation of water-filled and bifluidic sponge-like nanostructured network,
driven by the tuning of electrostatic interactions between the polyelectrolyte
constituents or their complexes may be a common feature of complex coacervate
fluids that display low fluid viscosity and low interfacial tension, but more
studies are needed to verify the generality of these observations. In this
review, we summarize representative studies of interfacial tension and
ultrastructures of complex coacervate fluids. We highlight that a consensus
property of the complex coacervate fluid is the observation of high or even bulk
like water dynamics within the dense complex coacervate phase that is consistent
with a low cohesive energy fluid. Our own studies on this subject are enabled by
the application of magnetic resonance relaxometry methods relying on spin labels
tethered to polyelectrolyte constituents or added as spin labeled probe molecules
that partition into the dense versus the equilibrium coacervate phase, permitting
the extraction of information on local polymer dynamics, polymer packing and
local water dynamics. We conclude with a snapshot of our current perspective on
the molecular and structural bases of the low interfacial tension of complex
coacervate fluids.
PMID- 27499327
TI - Deciphering Variability of PKD1 and PKD2 in an Italian Cohort of 643 Patients
with Autosomal Dominant Polycystic Kidney Disease (ADPKD).
AB - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common
hereditary kidney disease. We analysed PKD1 and PKD2, in a large cohort of 440
unrelated Italian patients with ADPKD and 203 relatives by direct sequencing and
MLPA. Molecular and detailed phenotypic data have been collected and submitted to
the PKD1/PKD2 LOVD database. This is the first large retrospective study in
Italian patients, describing 701 variants, 249 (35.5%) already associated with
ADPKD and 452 (64.5%) novel. According to the criteria adopted, the overall
detection rate was 80% (352/440). Novel variants with uncertain significance were
found in 14% of patients. Among patients with pathogenic variants, in 301 (85.5%)
the disease is associated with PKD1, 196 (55.7%) truncating, 81 (23%) non
truncating, 24 (6.8%) IF indels, and in 51 (14.5%) with PKD2. Our results outline
the high allelic heterogeneity of variants, complicated by the presence of
variants of uncertain significance as well as of multiple variants in the same
subject. Classification of novel variants may be particularly cumbersome having
an important impact on the genetic counselling. Our study confirms the importance
to improve the assessment of variant pathogenicity for ADPKD; to this point
databasing of both clinical and molecular data is crucial.
PMID- 27499329
TI - Crosstalk between Beclin-1-dependent autophagy and caspase-dependent apoptosis
induced by tanshinone IIA in human osteosarcoma MG-63 cells.
AB - The aim of the present study was to ascertain whether or not autophagy is induced
by tanshinone IIA (TanIIA), and to explore the crosstalk between autophagy and
apoptosis in regards to the antitumor effects of TanIIA on MG-63 cells and the
potential mechanism. MG-63 cells were cultured in vitro with various
concentrations of TanIIA (0, 2.5, 5, 10 and 20 mg/l) for 0, 24, 48 and 72 h,
respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT
assay was used to evaluate the inhibition of the proliferation of osteosarcoma MG
63 cells by TanIIA or in the presence/absence of chloroquine (CQ). Autophagic
vacuoles and characteristic autophagosomes were observed by transmission electron
microscopy (TEM). TanIIA-induced autophagy in MG-63 cells was confirmed by GFP
LC3 punctate fluorescence. The expression levels of apoptosis-related proteins
caspase-3, caspase-8, caspase-9 and cleaved-PARP and autophagy-related proteins
LC3II/LC3I and Beclin-1 were detected by western blotting. FITC-Annexin
V/propidium iodide (PI) staining, flow cytometry and Hoechst 33258 staining were
used to analyze the apoptotic rate. Fluorescence intensity of reactive oxygen
species (ROS) was examined under a fluorescence microscope using an analysis
software system. Cell proliferation was obviously inhibited by TanIIA in a dose-
and time-dependent manner. Generation of autophagy was triggered by TanIIA (0-20
mg/l) treatment, and in a Beclin-1-dependent manner. Compared with the control
group, the apoptosis ratio following treatment with 2.5 mg/l TanIIA failed to
achieve statistical significance. Expression of caspase-3, -8 and -9, and cleaved
PARP in the other groups was gradually enhanced in dose-dependent manner. Our
analysis also suggested that the influence of autophagy on TanIIA cytotoxicity
had a phase effect; with low-dose drugs and shorter treatment periods, autophagy
functioned as a damage repair mechanism. In conrast, when the cells were treated
with higher doses of TanIIA for longer treatment periods, autophagic cell death
contributed to apoptosis. Furthermore, generation of ROS occurred in a dose
dependent manner and pretreatment with NAC, a selective ROS scavenger, blocked
the coexistence of Beclin-1 autophagy and caspase-dependent apoptosis. In
conclusion, our findings provide strong evidence that TanIIA may be a potential
therapeutic drug against osteosarcoma. Moreover, its cytotoxity can be enhanced
with ROS agonists.
PMID- 27499330
TI - Non-ceruloplasmin bound copper and ATP7B gene variants in Alzheimer's disease.
AB - ATP7B, a protein mainly expressed in the hepatocytes, is a copper chaperone that
loads the metal into the serum copper-protein ceruloplasmin during its synthesis
and also escorts superfluous copper into the bile, by a sophisticated trafficking
mechanism. Impaired function of this ATPase is associated with a well-known
inborn error of copper metabolism, Wilson's disease (WD). Several mutations of
ATP7B are known, involving different regions of the protein, thus resulting in a
plethora of phenotypes in WD patients. It is a consolidated notion that copper
dysmetabolism occurs in Alzheimer's disease (AD) as well. Besides the molecular
mechanisms relating copper to the protein hallmarks of this disease and
neurodegeneration, more recently the observation that a free-copper in the serum,
not bound to ceruloplasmin (non-Cp-Cu), characterizes AD patients, prompted our
research to identify possible genetic defects of the ATP7B gene in AD patients.
Four specific single nucleotide polymorphisms and a WD rare mutation have a
statistical association with AD. They contribute to characterize a copper subtype
of AD. Additional facets of this AD phenotype, typified by higher levels of non
Cp-Cu, are presented and discussed in the framework of copper failure as an
accelerator risk factor of neurological disorders with different aetiology.
PMID- 27499331
TI - Clinical disposition, metabolism and in vitro drug-drug interaction properties of
omadacycline.
AB - 1. Absorption, distribution, metabolism, transport and elimination properties of
omadacycline, an aminomethylcycline antibiotic, were investigated in vitro and in
a study in healthy male subjects. 2. Omadacycline was metabolically stable in
human liver microsomes and hepatocytes and did not inhibit or induce any of the
nine cytochrome P450 or five transporters tested. Omadacycline was a substrate of
P-glycoprotein, but not of the other transporters. 3. Omadacycline metabolic
stability was confirmed in six healthy male subjects who received a single 300 mg
oral dose of [14C]-omadacycline (36.6 MUCi). Absorption was rapid with peak
radioactivity (~610 ngEq/mL) between 1-4 h in plasma or blood. The AUClast of
plasma radioactivity (only quantifiable to 8 h due to low radioactivity) was 3096
ngEq h/mL and apparent terminal half-life was 11.1 h. Unchanged omadacycline
reached peak plasma concentrations (~563 ng/mL) between 1-4 h. Apparent plasma
half-life was 17.6 h with biphasic elimination. Plasma exposure (AUCinf) averaged
9418 ng h/mL, with high clearance (CL/F, 32.8 L/h) and volume of distribution
(Vz/F 828 L). No plasma metabolites were observed. 4. Radioactivity recovery of
the administered dose in excreta was complete (>95%); renal and fecal elimination
were 14.4% and 81.1%, respectively. No metabolites were observed in urine or
feces, only the omadacycline C4-epimer.
PMID- 27499332
TI - 18(th)World Congress of Psychophysiology (IOP2016), Havana, Cuba.
PMID- 27499334
TI - Isolation and Characterization of a Highly Mutated Chinese Isolate of Enterovirus
B84 from a Patient with Acute Flaccid Paralysis.
AB - Enterovirus B84 (EV-B84) is a newly identified serotype within the species
Enterovirus B (EV-B). To date, only ten nucleotide sequences of EV-B84 are
published and only one full-length genome sequence (the prototype strain) is
available in the GenBank database. Here, a highly mutated EV-B84 (strain
AFP452/GD/CHN/2004) was recovered from a patient with acute flaccid paralysis in
the Guangdong province of China in 2004 making this the first report of EV-B84 in
China. Sequence comparison and phylogenetic dendrogram analysis revealed high
variation from the global EV-B84 strains (African and Indian strains) and
frequent intertypic recombination in the non-structural protein region,
suggesting high genetic diversity in EV-B84. The Chinese EV-B84 strain,
apparently evolving independently of the other ten strains, strongly suggests
that the EV-B84 strain has been circulating for many years. However, the
extremely low isolation rate suggests that it is not a prevalent EV serotype in
China or worldwide. This study provides valuable information about the molecular
epidemiology of EV-B84 in China, and will be helpful in future studies to
understand the association of EV-B84 with neurological disorders; it also helps
expand the number of whole virus genome sequences of EV-B84 in the GenBank
database.
PMID- 27499336
TI - Migration of an ingested fish bone into the paraglottic space.
AB - BACKGROUND: Ingested foreign bodies are common emergencies encountered in
otolaryngology practice. The vast majority can be managed with endoscopic
removal. Migration of foreign bodies into the paraglottic space is a rare event
that often necessitates using a more invasive procedure for removal. CASE REPORT:
A 68-year-old man presented with sore throat and odynophagia 4 days after
ingesting a fish bone. RESULTS: A computed tomography scan revealed a 2.5 cm
linear foreign body embedded in the larynx within the right paraglottic space.
The patient underwent endoscopic examination and transcervical exploration of the
paraglottic space via a posterolateral approach, with successful removal of the
foreign body on the second attempt. CONCLUSION: This is the first case report of
an ingested paraglottic space foreign body managed by transcervical exploration
using a posterolateral approach to the paraglottic space.
PMID- 27499337
TI - Effects of Carnitine on Valproic Acid Pharmacokinetics in Rats.
AB - The long-term administration of valproic acid (VPA) may decrease the plasma
concentrations of l-carnitine in epileptic patients. l-Carnitine is essential for
the beta-oxidation of fatty acids. The aim of this study is to determine whether
endogenous l-carnitine affects the pharmacokinetics of VPA in l-carnitine
deficient (CD) rats. An l-carnitine deficiency was induced in rats using sodium
pivalate. The pharmacokinetics of VPA were examined following its intravenous or
oral administration to rats. The plasma and urine concentrations of VPA and its
metabolites were determined using gas chromatography-mass spectrometry methods.
Plasma VPA concentrations were slightly higher in CD rats than in control rats,
whereas no significant differences were observed in the area under the curve or
mean residence times of VPA between the 2 groups. After i.v. administration, the
slope of the elimination phase (k) was significantly higher in CD rats than in
control rats (p < 0.01). Some of the beta-oxidation metabolites of VPA in plasma
and urine decreased, while the glucuronide metabolites of VPA in urine increased
complementarily in CD rats. Based on these results, it was concluded that
hypocarnitinemia could affect the pharmacokinetics of VPA.
PMID- 27499335
TI - Resin embedded multicycle imaging (REMI): a tool to evaluate protein domains.
AB - Protein complexes associated with cellular processes comprise a significant
fraction of all biology, but our understanding of their heterogeneous
organization remains inadequate, particularly for physiological densities of
multiple protein species. Towards resolving this limitation, we here present a
new technique based on resin-embedded multicycle imaging (REMI) of proteins in
situ. By stabilizing protein structure and antigenicity in acrylic resins,
affinity labels were repeatedly applied, imaged, removed, and replaced. In
principle, an arbitrarily large number of proteins of interest may be imaged on
the same specimen with subsequent digital overlay. A series of novel preparative
methods were developed to address the problem of imaging multiple protein species
in areas of the plasma membrane or volumes of cytoplasm of individual cells. For
multiplexed examination of antibody staining we used straightforward
computational techniques to align sequential images, and super-resolution
microscopy was used to further define membrane protein colocalization. We give
one example of a fibroblast membrane with eight multiplexed proteins. A simple
statistical analysis of this limited membrane proteomic dataset is sufficient to
demonstrate the analytical power contributed by additional imaged proteins when
studying membrane protein domains.
PMID- 27499338
TI - New and Evolving Techniques for the Characterization of Peptide Therapeutics.
AB - Advances in technologies related to the design and manufacture of therapeutic
peptides have enabled researchers to overcome the biological and technological
challenges that have limited their application in the past. As a result, peptides
of increasing complexity have become progressively important against a variety of
disease targets. Developing peptide drug products brings with it unique
scientific challenges consistent with the unique physicochemical properties of
peptide molecules. The identification of the proper characterization tools is
required in order to develop peptide formulations with the appropriate stability,
manufacturability, and bioperformance characteristics. This knowledge supports
the build of critical quality attributes and, ultimately, regulatory
specifications. The purpose of this review article is to provide an overview of
the techniques that are employed for analytical characterization of peptide drug
products. The techniques covered are highlighted in the context of peptide drug
product understanding and include chemical and biophysical approaches. Emphasis
is placed on summarizing the recent literature experience in the field. Finally,
the authors provide regulatory perspective on these characterization approaches
and discuss some potential areas for further research in the field.
PMID- 27499339
TI - Who's responsible for publication ethics? All of us.
PMID- 27499340
TI - Quantitative parameters for the examination of InGaN QW multilayers by low-loss
EELS.
AB - We present a detailed examination of a multiple InxGa1-xN quantum well (QW)
structure for optoelectronic applications. The characterization is carried out
using scanning transmission electron microscopy (STEM), combining high-angle
annular dark field (HAADF) imaging and electron energy loss spectroscopy (EELS).
Fluctuations in the QW thickness and composition are observed in atomic
resolution images. The impact of these small changes on the electronic properties
of the semiconductor material is measured through spatially localized low-loss
EELS, obtaining band gap and plasmon energy values. Because of the small size of
the InGaN QW layers additional effects hinder the analysis. Hence, additional
parameters were explored, which can be assessed using the same EELS data and give
further information. For instance, plasmon width was studied using a model-based
fit approach to the plasmon peak; observing a broadening of this peak can be
related to the chemical and structural inhomogeneity in the InGaN QW layers.
Additionally, Kramers-Kronig analysis (KKA) was used to calculate the complex
dielectric function (CDF) from the EELS spectrum images (SIs). After this
analysis, the electron effective mass and the sample absolute thickness were
obtained, and an alternative method for the assessment of plasmon energy was
demonstrated. Also after KKA, the normalization of the energy-loss spectrum
allows us to analyze the Ga 3d transition, which provides additional chemical
information at great spatial resolution. Each one of these methods is presented
in this work together with a critical discussion of their advantages and
drawbacks.
PMID- 27499341
TI - Ovarian cancer in the older woman.
AB - Ovarian cancer is the seventh most common cancer in women worldwide and accounts
for nearly 4% of all new cases of cancer in women. Almost half of all patients
with ovarian cancer are over the age of 65 at diagnosis, and over 70% of deaths
from ovarian cancer occur in this same age group. As the population ages, the
number of older women with ovarian cancer is increasing. Compared to younger
women, older women with ovarian cancer receive less surgery and chemotherapy,
develop worse toxicity, and have poorer outcomes. They are also significantly
under-represented in clinical trials and thus application of standard treatment
regimens can be challenging. Performance status alone has been shown to be an
inadequate tool to predict toxicity of older patients from chemotherapy. Use of
formal geriatric assessment tools is a promising direction for stratifying older
patients on trials. Elderly-specific trials, adjustments to the eligibility
criteria, modified treatment regimens, and interventions to decrease morbidities
in the vulnerable older population should be encouraged.
PMID- 27499342
TI - Fluorescence based Aptasensors for the determination of hepatitis B virus e
antigen.
AB - This research is aimed at selecting specific aptamer of hepatitis B e antigen by
SELEX and its applications. Hepatitis B e antigen (HBeAg) seroconversion is used
as an indicator of virological response when treating patients suffering from
chronic hepatitis B. HBeAg also indicates a high viremia and high infectivity in
untreated patients. With HBeAg modified magnetic beads as targets, three groups
of aptamers are successfully selected. These are the first reported DNA aptamers
that can specifically bind to HBeAg. Based on the property that the conformation
changes upon binding to its target, aptamer has emerged as ideal candidate in a
variety of sensing applications. In this study, we present a simple strategy for
aptamer-based fluorescence biosensors for the quantitative detection of HBeAg, in
which a fluorescence labeled HBeAg aptamer serves as the molecular recognition
element and a short DNA molecule that is complementary to the aptamer serves as
the competitor. The LOD for HBeAg is 609 ng/mL. Later, the fluorescence system is
deployed in HBeAg positive and negative blood serum (p < 0.05). The total
detection assay could be completed in 2 min. These newly isolated aptamers could
assist the diagnosis of chronic hepatitis B.
PMID- 27499343
TI - Dynamic Variables Fail to Predict Fluid Responsiveness in an Animal Model With
Pericardial Effusion.
AB - OBJECTIVES: The reliability of dynamic and volumetric variables of fluid
responsiveness in the presence of pericardial effusion is still elusive. The aim
of the present study was to investigate their predictive power in a porcine model
with hemodynamic relevant pericardial effusion. DESIGN: A single-center animal
investigation. PARTICIPANTS: Twelve German domestic pigs. INTERVENTIONS: Pigs
were studied before and during pericardial effusion. Instrumentation included a
pulmonary artery catheter and a transpulmonary thermodilution catheter in the
femoral artery. Hemodynamic variables like cardiac output (COPAC) and stroke
volume (SVPAC) derived from pulmonary artery catheter, global end-diastolic
volume (GEDV), stroke volume variation (SVV), and pulse-pressure variation (PPV)
were obtained. MEASUREMENTS AND MAIN RESULTS: At baseline, SVV, PPV, GEDV, COPAC,
and SVPAC reliably predicted fluid responsiveness (area under the curve 0.81 [p =
0.02], 0.82 [p = 0.02], 0.74 [p = 0.07], 0.74 [p = 0.07], 0.82 [p = 0.02]). After
establishment of pericardial effusion the predictive power of dynamic variables
was impaired and only COPAC and SVPAC and GEDV allowed significant prediction of
fluid responsiveness (area under the curve 0.77 [p = 0.04], 0.76 [p = 0.05], 0.83
[p = 0.01]) with clinically relevant changes in threshold values. CONCLUSIONS: In
this porcine model, hemodynamic relevant pericardial effusion abolished the
ability of dynamic variables to predict fluid responsiveness. COPAC, SVPAC, and
GEDV enabled prediction, but their threshold values were significantly changed.
PMID- 27499344
TI - Giant Peripheral Pulmonary Artery Aneurysm Rupture Under Anesthesia-A Sequela of
Positive-Pressure Ventilation.
PMID- 27499345
TI - Demographics and Scholarly Productivity of American Board of Anesthesiology
Volunteers: Results of an Internet-Based Bibliometric Analysis.
AB - OBJECTIVE: The American Board of Anesthesiology (ABA) has been responsible for
certification of anesthesiologists since 1938. Selected ABA diplomates provide
their expertise to write the ABA's written and oral examinations and to
administer the oral examination required for primary certification. The
demographics, administrative and educational duties, and scholarly productivity
of ABA volunteers and their dependence on subspecialty certification,
transesophageal echocardiography (TEE) credentials, and grant funding are
unknown. DESIGN: Observational study. SETTING: Internet analysis. PARTICIPANTS:
ABA volunteers who participated in the 2015 primary certification examinations
identified from the 2016 issue of ABA News. INTERVENTIONS: None. MEASUREMENTS AND
MAIN RESULTS: The 2016 issue of ABA News was downloaded from the public ABA
website and was used to identify all volunteers who participated in any aspect of
the 2015 primary certification process. Each individual's practice type, faculty
rank if applicable, and affiliation were identified using Google with the keyword
"anesthesiology." The practice location, time, and interval after original ABA
certification; additional ABA subspecialty certification; the number of
publications and citations; publication rate; citations per publication; and the
H-, M-, and i-10 indices were obtained using the ABA and Scopus databases.
Credentials in TEE were identified for each individual using the National Board
of Echocardiography database. National Institutes of Health (NIH) and Foundation
for Anesthesia Education and Research (FAER) funding for each volunteer was
evaluated using NIH Research Portfolio Online Reporting Tools and the FAER alumni
databases, respectively. Three hundred ninety-three ABA volunteers were
identified and analyzed. Three hundred ten individuals currently hold academic
appointments (83.5%), whereas 83 (16.5%) hold private practice or military
positions. Sixty-seven volunteers have major administrative roles (eg, dean,
chief executive officer, associate or assistant dean, chair, vice chair). Thirty
five individuals are program directors of anesthesiology residencies or
fellowships. Volunteers published 10,072 manuscripts that have been cited 194,835
times. Volunteers also received 51 NIH grants and 36 FAER grants. The median H-,
M-, and i10-indices of volunteers were 4, 0, and 3, respectively. Scholarly
productivity was dependent on academic rank, career duration, additional degrees,
and extramural funding, but not on practice location, subspecialty certification,
TEE credentials, or sex. CONCLUSIONS: These results indicated that ABA volunteers
are leaders in anesthesiology with established records of administrative,
educational, and scholarly accomplishment.
PMID- 27499347
TI - Why Are There Different Languages? The Role of Adaptation in Linguistic
Diversity.
AB - Why are there different languages? A common explanation is that different
languages arise from the gradual accumulation of random changes. Here, we argue
that, beyond these random factors, linguistic differences, from sounds to
grammars, may also reflect adaptations to different environments in which the
languages are learned and used. The aspects of the environment that could shape
language include the social, the physical, and the technological.
PMID- 27499346
TI - Worldwide Opinion on Multicenter Randomized Interventions Showing Mortality
Reduction in Critically Ill Patients: A Democracy-Based Medicine Approach.
AB - OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine
(systematic review), expert assessment, and worldwide voting by physicians to
express their opinions and self-reported practice via the Internet. The authors
applied democracy-based medicine to key trials in critical care medicine. DESIGN
AND SETTING: A systematic review of literature followed by web-based voting on
findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from
61 countries. INTERVENTIONS: The authors performed a systematic literature review
(via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter
randomized clinical trials in critical care that reported a significant effect on
survival and were endorsed by expert clinicians. Then they solicited voting and
self-reported practice on such evidence via an interactive Internet
questionnaire. Relationships among trial sample size, design, and respondents'
agreement were investigated. The gap between agreement and use/avoidance and the
influence of country origin on physicians' approach to interventions also were
investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter
randomized controlled trials, 15 interventions affecting mortality were
identified. Wide variabilities in both the level of agreement and reported
practice among different interventions and countries were found. Moreover,
agreement and reported practice often did not coincide. Finally, a positive
correlation among agreement, trial sample size, and number of included centers
was found. On the contrary, trial design did not influence clinicians' agreement.
CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary
among different interventions and countries. The role of these interventions in
affecting survival should be further investigated to reduce both the gap between
evidence and clinical practice and transnational differences.
PMID- 27499348
TI - The Psychology and Neuroscience of Financial Decision Making.
AB - Financial decisions are among the most important life-shaping decisions that
people make. We review facts about financial decisions and what cognitive and
neural processes influence them. Because of cognitive constraints and a low
average level of financial literacy, many household decisions violate sound
financial principles. Households typically have underdiversified stock holdings
and low retirement savings rates. Investors overextrapolate from past returns and
trade too often. Even top corporate managers, who are typically highly educated,
make decisions that are affected by overconfidence and personal history. Many of
these behaviors can be explained by well-known principles from cognitive science.
A boom in high-quality accumulated evidence-especially how practical, low-cost
'nudges' can improve financial decisions-is already giving clear guidance for
balanced government regulation.
PMID- 27499349
TI - Sulforaphane increases the efficacy of anti-androgens by rapidly decreasing
androgen receptor levels in prostate cancer cells.
AB - Prostate cancer (PCa) cells utilize androgen for their growth. Hence, androgen
deprivation therapy (ADT) using anti-androgens, e.g. bicalutamide (BIC) and
enzalutamide (ENZ), is a mainstay of treatment. However, the outgrowth of
castration resistant PCa (CRPC) cells remains a significant problem. These CRPC
cells express androgen receptor (AR) and utilize the intratumoral androgen
towards their continued growth and invasion. Sulforaphane (SFN), a naturally
occurring isothiocyanate found in cruciferous vegetables, can decrease AR protein
levels. In the present study, we tested the combined efficacy of anti-androgens
and SFN in suppressing PCa cell growth, motility and clonogenic ability. Both
androgen-dependent (LNCaP) and androgen-independent (C4-2B) cells were used to
monitor the effects of BIC and ENZ, alone and in combination with SFN. Co
exposure to SFN significantly (p<0.005) enhanced the anti-proliferative effects
of anti-androgens and downregulated expression of the AR-responsive gene,
prostate specific antigen (PSA) (p<0.05). Exposure to SFN decreased AR protein
levels in a time- and dose-dependent manner with almost no AR detected at 24 h
with 15 uM SFN (p<0.005). This rapid and potent AR suppression by SFN occurred by
both AR protein degradation, as suggested by cycloheximide (CHX) co-exposure
studies, and by suppression of AR gene expression, as evident from quantitative
RT-PCR experiments. Pre-exposure to SFN also reduced R1881-stimulated nuclear
localization of AR, and combined treatment with SFN and anti-androgens abrogated
the mitogenic effects of this AR-agonist (p<0.005). Wound-healing assays revealed
that co-exposure to SFN and anti-androgens can significantly (p<0.005) reduce PCa
cell migration. In addition, long-term exposures (14 days) to much lower
concentrations of these agents, SFN (0.2 uM), BIC (1 uM) and/or ENZ (0.4 uM)
significantly (p<0.005) decreased the number of colony forming units (CFUs).
These findings clearly suggest that SFN may be used as a promising adjunct agent
to augment the efficacy of anti-androgens against aggressive PCa cells.
PMID- 27499350
TI - Mental illness and the right to vote: a review of legislation across the world.
AB - The right to vote is an important right signifying freedom of thought as well as
full citizenship in any setting. Right to vote is enshrined and protected by
international human rights treaties. The right of 'everyone' to take part in the
political process and elections is based on universal and equal suffrage.
Although these International Conventions have been ratified by the large majority
of United Nations Member States, their application across the globe is by no
means universal. This study sets out to examine the domestic laws of UN Member
States in order to explore whether individuals with mental health problems have
the right to vote in actuality and, thu,s can participate in political life.
Through various searches, electoral laws and Constitutions of 193 Member States
of the United Nations were studied. The authors were able to find legislation
and/or Constitutional provisions in 167 of the 193 Member States. Twenty-one
countries (11%) only placed no restrictions on the right to vote by persons with
mental health problems. Over one third of the countries (36%) deny all persons
with any mental health problems a right to vote without any qualifier. Some of
these discriminatory attitudes are reflected in the multiplicity of terms used to
describe persons with mental health problems. Another 21 countries (11%) denied
the right to vote to detained persons; of these, nine Member States specifically
denied the right to vote to persons who were detained under the mental health
law, while the remainder denied the right to vote to all those who were
interdicted or judicially interdicted. It would appear that in many countries the
denial of voting rights is attributed to a lack of ability to consent by the
individuals with mental illness. Further exploration of explanation is required
to understand these variations, which exist in spite of international treaties.
PMID- 27499351
TI - Molecular mechanism of hepatic steatosis: pathophysiological role of autophagy.
AB - Steatosis is an early characteristic in the pathogenesis of fatty liver disease
(FLD). Mechanisms of hepatic steatosis are aetiology-dependent. Activation of
autophagy in liver ameliorates hepatic steatosis. A modulation of hepatic
autophagy affects the degree of hepatocyte steatosis and the progression of FLD
as demonstrated by pre-clinical models and clinical trials. This review
summarises recent advances on pathophysiological roles of autophagy in hepatic
lipid metabolism. A comprehensive regulation of autophagic networks holds promise
for the improvement of hepatic steatosis. Autophagic signalling pathway may be a
novel therapeutic target against FLD. HIGHLIGHTS: * Hepatic steatosis is a
pathological condition wherein vacuoles of triglyceride (TG) fat are
overaccumulated in liver because of abnormal metabolism of lipids. * Hepatic
autophagy regulates lipid metabolism as demonstrated by macrolipophagy in
response to starvation and hepatic overabundance of TG in obesity. * Autophagic
signals are closely associated with apoptotic pathways. There is distinctive
relationship between hepatic autophagy and apoptosis, which affects the
progression of fatty liver. * Regulation of autophagic process can be a novel
therapeutic strategy for fatty liver disease.
PMID- 27499352
TI - Nonionic surfactant structure on the drug release, formulation and physical
properties of ethylcellulose microspheres.
AB - Evaluate the effects of nonionic surfactants Brij 58 and Tween 40 with different
structures but similar hydrophilic lipophilic balances (HLBs) on theophylline
(TH)-loaded ethylcellulose (EC) microspheres. Microspheres were formulated using
ratios of the surfactants with matching HLB values but different chemical
structures at temperatures (22/35 degrees C) by hydrophobic solvent-emulsion
evaporation. Particle size, GMD, drug loading, encapsulation efficiency and
dissolution were evaluated. Drug release was determined using the zero- and first
order, Higuchi and Hixson-Crowell models. EC microspheres prepared with
surfactant Brij 58 showed discrete, free-flowing spherical particles, solid
interiors and increased particle smoothness as temperature increased; those
prepared with Tween 40 appeared porous with coarser surface morphology as
temperature increased; both were CHLB (Combined HLB) dependent. Dissolution
obeyed the Higuchi model drug release for both microspheres prepared with Tween
40 and Brij 58 except for those prepared with Brij 58 at 35 degrees C, which
presented as zero order. The results were ascribed to the different chemical
structure of Brij 58 versus Tween 40 and preparation temperature. Surfactant
chemical structure is an unreported processing parameter shown here to be
important in microsphere formulation. Brij 58 possesses properties unique to its
chemical structure that influence pharmaceutical and molecular biopharmaceutical
research.
PMID- 27499353
TI - Wastewater Reuse for Agriculture: Development of a Regional Water Reuse Decision
Support Model (RWRM) for Cost-Effective Irrigation Sources.
AB - Water scarcity has become a critical problem in many semiarid and arid regions.
The single largest water use in such regions is for crop irrigation, which
typically relies on groundwater and surface water sources. With increasing stress
on these traditional water sources, it is important to consider alternative
irrigation sources for areas with limited freshwater resources. One potential
irrigation water resource is treated wastewater for agricultural fields located
near urban centers. In addition, treated wastewater can contribute an appreciable
amount of necessary nutrients for plants. The suitability of reclaimed water for
specific applications depends on water quality and usage requirements. The main
factors that determine the suitability of recycled water for agricultural
irrigation are salinity, heavy metals, and pathogens, which cause adverse effects
on human, plants, and soils. In this paper, we develop a regional water reuse
decision-support model (RWRM) using the general algebraic modeling system to
analyze the cost-effectiveness of alternative treatment trains to generate
irrigation water from reclaimed wastewater, with the irrigation water designed to
meet crop requirements as well as California's wastewater reuse regulations
(Title 22). Using a cost-minimization framework, least-cost solutions consisting
of treatment processes and their intensities (blending ratios) are identified to
produce alternative irrigation sources for citrus and turfgrass. Our analysis
illustrates the benefits of employing an optimization framework and flexible
treatment design to identify cost-effective blending opportunities that may
produce high-quality irrigation water for a wide range of end uses.
PMID- 27499354
TI - Effects of mutants in bHLH region on structure stability and protein-DNA binding
energy in DECs.
AB - The human DEC subfamily contains two highly conserved members belonging to basic
helix-loop-helix (bHLH) transcription factors. This conserved family is spread
widely among various species with the function of regulating various crucial
molecular signaling pathways. Due to the significance of DECs for important
biological processes, their relationship with diseases and the lack of
experimentally proven structures, we have implemented a comparative modeling for
the bHLH region of DECs as homodimers with themselves and heterodimers with HES
1. Three mutants with predicted roles in reducing intramolecular binding (H57A,
R65A, and LL7879AA in DEC1 and LL7071AA in DEC2) were investigated on DEC
monomers. Molecular dynamics (MD) simulations were also employed to evaluate the
behavior of the mutant molecules in aqueous solution. The monomer was divided
into subregions for accurate investigation. The fluctuation in the basic region
of mutants was higher than that of wild-type molecules. The binding energy value
between protein and DNA obviously increased in the homodimer harboring R65A
mutants, which led to more unstable status between protein and DNA. Thus, the
mutant R65A interfered DNA-binding affinity. A study on the spatial structures of
wild-type and mutant DECs may facilitate functional prediction for mutation
effects and dynamic behavior under various conditions and may ultimately help in
targeted drug design.
PMID- 27499355
TI - The global diabetes epidemic: what does it mean for infectious diseases in
tropical countries?
AB - Tropical countries are experiencing a substantial rise in type 2 diabetes, which
is often undiagnosed or poorly controlled. Since diabetes is a risk factor for
many infectious diseases, this increase probably adds to the large infectious
disease burden in tropical countries. We reviewed the literature to investigate
the interface between diabetes and infections in tropical countries, including
the WHO-defined neglected tropical diseases. Although solid data are sparse,
patients with diabetes living in tropical countries most likely face increased
risks of common and health-care-associated infections, as well as infected foot
ulcers, which often lead to amputation. There is strong evidence that diabetes
increases the severity of some endemic infections such as tuberculosis,
melioidosis, and dengue virus infection. Some HIV and antiparasitic drugs might
induce diabetes, whereas helminth infections appear to afford some protection
against future diabetes. But there are no or very scarce data for most tropical
infections and for possible biological mechanisms underlying associations with
diabetes. The rise in diabetes and other non-communicable diseases puts a heavy
toll on health systems in tropical countries. On the other hand, complications
common to both diabetes and some tropical infections might provide an opportunity
for shared services-for example, for eye health (trachoma and onchocerciasis),
ulcer care (leprosy), or renal support (schistosomiasis). More research about the
interaction of diabetes and infections in tropical countries is needed, and the
infectious disease burden in these countries is another reason to step up global
efforts to improve prevention and care for diabetes.
PMID- 27499356
TI - Dosimetric characteristics of four PTW microDiamond detectors in high-energy
proton beams.
AB - Small diamond detectors are useful for the dosimetry of high-energy proton beams.
However, linear energy transfer (LET) dependence has been observed in the
literature with such solid state detectors. A novel synthetic diamond detector
has recently become commercially available from the manufacturer PTW-Freiburg
(PTW microDiamond type 60019). This study was designed to thoroughly characterize
four microDiamond detectors in clinical proton beams, in order to investigate
their response and their reproducibility in high LET regions. Very good
dosimetric characteristics were observed for two of them, with good stability of
their response (deviation less than 0.4% after a pre-irradiation dose of
approximately 12 Gy), good repeatability (coefficient of variation of 0.06%) and
a sensitivity of approximately 0.85 nC Gy(-1). A negligible dose rate dependence
was also observed for these two microDiamonds with a deviation of the sensitivity
less than 0.7% with respect to the one measured at the reference dose rate of
2.17 Gy min(-1), in the investigated dose rate range from 1.01 Gy min(-1) to 5.52
Gy min(-1). Lateral dose profile measurements showed the high spatial resolution
of the microDiamond oriented with its stem perpendicular to the beam axis and
with its small sensitive thickness of about 1 MUm in the scanning profile
direction. Finally, no significant LET dependence was found with these two
diamond dosimeters in comparison to a reference ionization chamber (model IBA
PPC05). These good results were in accordance to the literature. However, this
study showed also a non reproducibility between the devices in terms of
stability, sensitivity and LET dependence, since the two other microDiamonds
characterized in this work showed different dosimetric characteristics making
them not suitable for proton beam dosimetry with a maximum difference of the peak
to-plateau ratio of 6.7% relative to the reference ionization chamber in a
clinical 138 MeV proton beam.
PMID- 27499357
TI - The EGFR pathway is involved in the regulation of PD-L1 expression via the IL
6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer.
AB - Negative regulation of the signal mediated by the programmed cell death protein 1
(PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the
function of T and B cells, which play a key role in the regulation of immune
response. Recently, emerging evidence has suggested that the expression of PD-L1
is related to the mutation status of the epidermal growth factor receptor (EGFR).
Moreover, the activation of the EGFR signaling pathway can induce expression of
PD-L1. In the present study, we demonstrated that activated EGFR can upregulate
the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer
and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small
cell lung cancer (NSCLC) cells. Cells treated with epidermal growth factor
receptor tyrosine kinase inhibitors (EGFR-TKIs) can downregulate the activation
of the IL-6/JAK/STAT3 pathway, which subsequently reduces the expression of PD
L1. Furthermore, silencing of PD-L1 expression in NSCLC cells correlated with
inhibition of cell proliferation and enhanced tumor cell apoptosis. In summary,
our research indicates that EGFR is involved in the regulation of PD-L1
expression and cell proliferation via the IL-6/JAK/STAT3 signaling pathway in
NSCLC. The present study suggests the potential of combined targeted therapy with
immunotherapy in the treatment of NSCLC.
PMID- 27499358
TI - Characteristics of a professional: survey of primary care and non-primary care
residents.
PMID- 27499359
TI - The unique fluorine effects in organic reactions: recent facts and insights into
fluoroalkylations.
AB - Fluoroalkylation reaction, featuring the transfer of a fluoroalkyl group to a
substrate, is a straightforward and efficient method for the synthesis of
organofluorine compounds. In fluoroalkylation reactions, fluorine substitution
can dramatically influence the chemical outcome. On the one hand, the chemistry
of alkylation with non-fluorinated reagents may not be applicable to
fluoroalkylations, so it is necessary to tackle the fluorine effects to achieve
efficient fluoroalkylation reactions. On the other hand, fluorine substitution
may bring about new reactivities and transformations that cannot be realized in
alkylation with non-fluorinated reagents; thus, fluorine substitution can be used
to explore new synthetic methods. This tutorial review provides a brief overview
of the unique fluorine effects in recently developed nucleophilic, electrophilic,
radical, and transition metal-mediated fluoroalkylation reactions by comparing
with either their non-fluorinated counterparts or fluorinated counterparts with
different numbers of fluorine substituents.
PMID- 27499361
TI - Safety and tolerability of long-acting injectable versus oral antipsychotics: A
meta-analysis of randomized controlled studies comparing the same antipsychotics.
AB - OBJECTIVE: We aimed to assess whether long-acting injectable antipsychotics
(LAIs), which are initiated in a loading strategy or overlapping with oral
antipsychotics (OAPs) and which cannot be stopped immediately, are associated
with greater safety/tolerability issues than OAPs. METHOD: Systematic review and
meta-analysis of randomized controlled trials (RCTs) comparing LAIs and OAPs,
including only LAI-OAP pairs of the same OAP (allowing oral risperidone and
paliperidone as comparators for either risperidone or paliperidone LAI). Primary
outcome was treatment discontinuation due to adverse events. Secondary outcomes
included serious adverse events, death, >=1 adverse event and individual adverse
event rates. RESULTS: Across 16 RCTs (n=4902, mean age=36.4years, males=65.8%,
schizophrenia=99.1%) reporting on 119 adverse event outcomes, 55 (46.2%) adverse
events were reported by >=2 studies allowing a formal meta-analysis. Out of all
119 reported adverse events, LAIs and OAPs did not differ significantly regarding
115 (96.6%). LAIs were similar to OAPs regarding the frequency of treatment
discontinuation due to adverse events, serious adverse events, all-cause death
and death for reasons excluding accident or suicide. Compared to OAPs, LAIs were
associated with significantly more akinesia, low-density lipoprotein cholesterol
change and anxiety. Conversely, LAIs were associated with significantly lower
prolactin change. CONCLUSION: LAIs and OAPs did not differ on all serious and
>90% of individual adverse events. However, more studies focusing on adverse
event frequencies, severity and time course associated with LAI vs OAP
formulations of the same antipsychotic are needed. Additionally, adverse events
data for LAIs after stopping overlapping oral antipsychotic treatment are needed.
PMID- 27499362
TI - Subcortical grey matter alterations in cocaine dependent individuals with
substance-induced psychosis compared to non-psychotic cocaine users.
AB - After prolonged psychostimulant abuse, transient psychotic symptoms referred to
as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms
observed in schizophrenia spectrum disorders. The comparability in psychotic
presentation between SIP and schizophrenias suggests that similar underlying
neural deficits may contribute to the expression of psychosis across these
disorders. To date, neuroanatomical characterization of grey matter structural
alterations in SIP has been limited to methamphetamine associated psychosis, with
no studies controlling for potential neurotoxic effects of the psychostimulant
that precipitates psychosis. To investigate grey matter subcortical alterations
in SIP, a voxel-based analysis of magnetic resonance images (MRI) was performed
between a group of 74 cocaine dependent nonpsychotic individuals and a group of
29 individuals with cocaine-associated psychosis. The cocaine-associated
psychosis group had significantly smaller volumes of the thalamus and left
hippocampus, controlling for age, total brain volume, current methamphetamine
dependence, and current marijuana dependence. No differences were present in
bilateral caudate structures. The findings of reduced thalamic and hippocampal
volumes agree with previous reports in the schizophrenia literature, suggesting
alterations of these structures are not specific to schizophrenia, but may be
common to multiple forms of psychosis.
PMID- 27499360
TI - Exploring the risk factors for differences in the cumulative incidence of coeliac
disease in two neighboring countries: the prospective DIABIMMUNE study.
AB - BACKGROUND: During the last several decades the prevalence of coeliac disease
(CD) has increased worldwide. AIM: To compare the cumulative incidence of CD
between Estonian and Finnish children and to identify the risk factors. MATERIALS
AND METHODS: Children were recruited as part of the DIABIMMUNE Study. In the
birth cohort (BC) 258 children from Estonia and 305 from Finland, and in the
young children's cohort (YCC) 1363 and 1384 children were followed up,
respectively. The diagnosis of CD was made in accordance with the ESPGHAN
guidelines-the presence of IgA-tTG antibodies and small bowel villous atrophy.
RESULTS: During the study period 29 children developed CD. The cumulative
incidence of CD was significantly higher in Finland (0.77% vs 0.27%; P=0.01). No
difference was seen between the children with CD and the controls in the duration
of breastfeeding or the age at cereal introduction. The BC children with CD had
had significantly more episodes of infections with fever by the age of 12 months
compared to the controls (3.4 vs 1.4; P=0.04). CONCLUSION: The 5-year cumulative
incidence of childhood CD is significantly higher in Finland than in Estonia.
Sequential infections early in life may increase the risk for developing CD.
PMID- 27499363
TI - A workshop on leadership for senior MD-PhD students.
AB - Leadership skills are essential for a successful career as a physician-scientist,
yet many MD-PhD training programs do not offer formal training in leadership. The
Vanderbilt Medical Scientist Training Program (MSTP) previously established a 2
day leadership workshop that has been held biennially since 2006 for students in
the first and second years of the graduate school portion of combined MD and PhD
training (G1/G2 students). Workshop attendees have consistently rated this
workshop as a highly effective experience. However, opportunities for structured
training in leadership competencies during the subsequent 3-5 years of MD-PhD
training are limited. Given the success of the G1/G2 leadership workshop and the
need for continuity in this model of leadership training, we developed a half-day
workshop for MSTP students in the clinical years of medical school (M3/M4
students) to foster continued training in leadership. Our workshop curriculum,
based in part on original cases drafted by Vanderbilt MSTP students, provides
concrete strategies to manage conflict and navigate leadership transitions in the
physician-scientist career path. The curriculum emphasizes both short-term
competencies, such as effective participation as a member of a clinical team, and
long-term competencies, such as leadership of a research team, division, or
department. Our inaugural senior leadership workshop, held in August, 2015, was
judged by student participants to be well organized and highly relevant to
leadership concepts and skills. It will be offered biennially in our training
curriculum for M3 and M4 MSTP students.
PMID- 27499364
TI - What and how do students learn in an interprofessional student-run clinic? An
educational framework for team-based care.
AB - BACKGROUND: The student-run clinic (SRC) has the potential to address
interprofessional learning among health professions students. PURPOSE: To derive
a framework for understanding student learning during team-based care provided in
an interprofessional SRC serving underserved patients. METHODS: The authors
recruited students for a focus group study by purposive sampling and snowballing.
They constructed two sets of semi-structured questions for uniprofessional and
multiprofessional groups. Sessions were audiotaped, and transcripts were
independently coded and adjudicated. Major themes about learning content and
processes were extracted. Grounded theory was followed after data synthesis and
interpretation to establish a framework for interprofessional learning. RESULTS:
Thirty-six students from four professions (medicine, physician assistant,
occupational therapy, and pharmacy) participated in eight uniprofessional groups;
14 students participated in three multiprofessional groups (N = 50). Theme
saturation was achieved. Six common themes about learning content from
uniprofessional groups were role recognition, team-based care appreciation,
patient experience, advocacy-/systems-based models, personal skills, and career
choices. Occupational therapy students expressed self-advocacy, and medical
students expressed humility and self-discovery. Synthesis of themes from all
groups suggests a learning continuum that begins with the team huddle and
continues with shared patient care and social interactions. Opportunity to
observe and interact with other professions in action is key to the learning
process. DISCUSSION: Interprofessional SRC participation promotes learning 'with,
from, and about' each other. Participation challenges misconceptions and
sensitizes students to patient experiences, health systems, advocacy, and social
responsibility. Learning involves interprofessional interactions in the patient
encounter, reinforced by formal and informal communications. Participation is
associated with interest in serving the underserved and in primary care careers.
The authors proposed a framework for interprofessional learning with implications
for optimal learning environments to promote team-based care. Future research is
suggested to identify core faculty functions and best settings to advance and
enhance student preparation for future collaborative team practice.
PMID- 27499366
TI - Is there a role for gut microbiota in type 1 diabetes pathogenesis?
AB - Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by
insufficient insulin production due to the destruction of insulin secreting beta
cells in the Langerhans islets. A variety of factors, including chemicals,
viruses, commensal bacteria and diet have been proposed to contribute to the risk
of developing the disorder. In the last years, gut microbiota has been proposed
as a main factor in T1D pathogenesis. Several alterations of gut microbiota
composition were described both in animal model and in humans. The decrease of
Firmicutes/Bacteroides ratio was the most frequent pattern described, in
particular, in human studies. Furthermore, Bacteroides, Clostridium cluster XIVa,
Lactobacillus, Bifidobacterium, and Prevotella relative abundances were different
in healthy and affected subjects. Dysbiosis would seem to increase intestinal
permeability and thus promote the development of a pro-inflammatory niche that
stimulates beta-cell autoimmunity in predisposed subjects. Preliminary studies on
animal models were realized to investigate the role of gut microbiota modulation
as therapy or prevention approach in predisposed animals: promising and
stimulating results have been reported. Key message Dietary antigens and
microbiota-derived products might act as triggers of T1D by causing a pro
inflammatory and metabolic dysfunctional environment.
PMID- 27499367
TI - miR-17 inhibits ovarian cancer cell peritoneal metastasis by targeting ITGA5 and
ITGB1.
AB - An essential step in the peritoneal spread of ovarian cancer is the adhesion and
implantation of tumor cells to the mesothelium layer. Integrin alpha5 and beta1
have been reported to mediate the initial adhesion process and to correlate with
disease survival in ovarian cancer. However, the molecular mechanism of integrin
alpha5beta1 dysregulation in tumorigenesis and metastasis remained enigmatic. In
the present study, using the US NCI60 database, we identified miR-17 as a
candidate regulator targeting both integrin alpha5 and beta1. The level of miR-17
was evidently inversely correlated with that of alpha5 and beta1 in ovarian
cancer cell lines. Specifically, miR-17 bound directly to the 3' untranslated
region (3'UTR) of alpha5 and beta1 and suppressed their expression. Forced
expression of miR-17 led to markedly diminished adhesion and invasion of ovarian
cancer cells in vitro, and notably reduced metastatic nodules inside the
peritoneal cavity in in vivo SKOV3 xenografts model. Moreover, ectopic expression
of miR-17 in ovarian cancer cells resulted in repressed ILK phosphorylation as
well as decreased production of active matrix metalloproteinase-2 (MMP-2). Our
results indicated that miR-17 hampered ovarian cancer peritoneal propagation by
targeting integrin alpha5 and beta1. These findings supported the utility of miR
17/alpha5beta1 to be considered as valuable marker for metastatic potential of
ovarian cancer cells, or a therapeutic target in ovarian cancer treatment.
PMID- 27499365
TI - Real-time optical diagnosis of gastric cancer with serosal invasion using
multiphoton imaging.
AB - A real-time optical biopsy, which could determine tissue histopathology, would be
of extraordinary benefit to staging laparoscopy for gastric cancer with serosal
invasion (T4) that requires downstage treatment. We investigated the feasibility
of using multiphoton imaging to perform a real-time optical diagnosis of gastric
cancer with or without serosal invasion. First, a pilot study was performed to
establish the optical diagnostic features of gastric cancer with or without
serosal invasion using multiphoton imaging compared with hematoxylin-eosin
staining and Masson's trichrome staining. Second, a blinded study was performed
to compare the diagnostic sensitivity, specificity, and accuracy of multiphoton
imaging and endoscopic ultrasonography (EUS) for T4 gastric cancer. In the pilot
study, multiphoton imaging revealed collagen loss and degradation and cellular
and nuclear pleomorphism in gastric cancer with serosal invasion. The collagen
content in gastric cancer with or without serosal invasion was 0.36 +/- 0.18 and
0.79 +/- 0.16 (p < 0.001), respectively. In the blinded study, the sensitivity,
specificity, and accuracy of EUS and multiphoton imaging for T4 gastric cancer
were 70% and 90% (p = 0.029), 66.67% and 96.67% (p = 0.003), and 68.33% and
93.33% (p = 0.001), respectively. It is feasible to use multiphoton imaging to
make a real-time optical diagnosis of gastric cancer with or without serosal
invasion.
PMID- 27499368
TI - In vitro cytotoxicity of novel 2,5,7-tricarbo-substituted indoles derived from 2
amino-5-bromo-3-iodoacetophenone.
AB - A series of novel 2,5,7-tricarbo-substituted indoles were prepared via sequential
Sonogashira and Suzuki-Miyaura cross-coupling of 2-amino-5-bromo-3
iodoacetophenone with terminal acetylenes and aryl/styrylboronic acids followed
by palladium chloride-mediated heteroannulation of the incipient 5-aryl/styryl
substituted 2-amino-3-(arylalkynyl)acetophenones. These polycarbo-substituted
indole derivatives were evaluated for potential in vitro antiproliferative
activity against the human breast adenocarcinoma (MCF-7) and human cervical
cancer (HeLa) cell lines. Compounds 6f, 6i, 6k, 6m and 6n were found to exhibit
significant cytotoxicity and selectivity against the HeLa cells. Compounds 6i and
6m were chosen as representative examples to evaluate their pro-apoptotic
efficacy against the HeLa cell line. The compounds induced apoptosis through cell
membrane alteration and DNA fragmentation caspase-dependent pathways.
PMID- 27499370
TI - Comparison between beta radiation dose distribution due to LDR and HDR ocular
brachytherapy applicators using GATE Monte Carlo platform.
AB - Eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are generally used
in brachytherapy for the treatment of eye diseases as uveal melanoma. Whenever,
radiation is used in treatment, dosimetry is essential. However, knowledge of the
exact dose distribution is a critical decision-making to the outcome of the
treatment. The Monte Carlo technique provides a powerful tool for calculation of
the dose and dose distributions which helps to predict and determine the doses
from different shapes of various types of eye applicators more accurately. The
aim of this work consisted in using the Monte Carlo GATE platform to calculate
the 3D dose distribution on a mathematical model of the human eye according to
international recommendations. Mathematical models were developed for four
ophthalmic applicators, two HDR 90Sr applicators SIA.20 and SIA.6, and two LDR
106Ru applicators, a concave CCB model and a flat CCB model. In present work,
considering a heterogeneous eye phantom and the chosen tumor, obtained results
with the use of GATE for mean doses distributions in a phantom and according to
international recommendations show a discrepancy with respect to those specified
by the manufacturers. The QC of dosimetric parameters shows that contrarily to
the other applicators, the SIA.20 applicator is consistent with recommendations.
The GATE platform show that the SIA.20 applicator present better results, namely
the dose delivered to critical structures were lower compared to those obtained
for the other applicators, and the SIA.6 applicator, simulated with MCNPX
generates higher lens doses than those generated by GATE.
PMID- 27499371
TI - CyberKnife beam output factor measurements: A multi-site and multi-detector
study.
AB - PURPOSE: New promising detectors are available for measuring small field size
output factors (OFs). This study focused on a multicenter evaluation of two new
generation detectors for OF measurements on CyberKnife systems. METHODS: PTW
60019 microDiamond and W1 plastic scintillation detector (PSD) were used to
measure OFs on eight CyberKnife units of various generations for 5-60mm fixed
cones. MicroDiamond and PSD OF were compared to routinely used silicon diodes
data corrected applying published Monte Carlo (MC) factors. PSD data were
corrected for Cerenkov Light Ratio (CLR). The uncertainties related to CLR
determination were estimated. RESULTS: Considering OF values averaged over all
centers, the differences between MC corrected diode and the other two detectors
were within 1.5%. MicroDiamond exhibited an over-response of 1.3% at 7.5mm and a
trend inversion at 5mm with a difference of 0.2%. This behavior was consistent
among the different units. OFs measured by PSD slightly under-responded compared
to MC corrected diode for the smaller cones and the differences were within 1%.
The observed CLR variability was 2.5% and the related variation in OF values was
1.9%. CONCLUSION: This study indicates that CyberKnife microDiamond OF require
corrections below 2%. The results are enhanced by the consistency observed among
different units. Scintillator shows a good agreement to MC corrected diode but
CLR determination remains critical requiring further investigations. The results
emphasized the value of a multi-center validation over a single center approach.
PMID- 27499369
TI - Ca-asp bound X-ray structure and inhibition of Bacillus anthracis dihydroorotase
(DHOase).
AB - Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis
pathway and is responsible for the reversible cyclization of carbamyl-aspartate
(Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes
based on several structural characteristics, one of which is the length of the
flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the
enzyme activity. Here, we present the crystal structure of Class I Bacillus
anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone
of glycine in the shorter loop forming the necessary hydrogen bonds with the
substrate, in place of the two threonines found in Class II DHOases. Despite the
differences in the catalytic loop, the structure confirms that the key
interactions between the substrate and active site residues are similar between
Class I and Class II DHOase enzymes, which we further validated by mutagenesis
studies. B. anthracis DHOase is also a potential antibacterial drug target. In
order to identify prospective inhibitors, we performed high-throughput screening
against several libraries using a colorimetric enzymatic assay and an orthogonal
fluorescence thermal binding assay. Surface plasmon resonance was used for
determining binding affinity (KD) and competition analysis with Ca-asp. Our
results highlight that the primary difference between Class I and Class II DHOase
is the catalytic loop. We also identify several compounds that can potentially be
further optimized as potential B. anthracis inhibitors.
PMID- 27499373
TI - Origin of Pressure-induced Superconducting Phase in KxFe2-ySe2 studied by
Synchrotron X-ray Diffraction and Spectroscopy.
AB - Pressure dependence of the electronic and crystal structures of KxFe2-ySe2, which
has pressure-induced two superconducting domes of SC I and SC II, was
investigated by x-ray emission spectroscopy and diffraction. X-ray diffraction
data show that compressibility along the c-axis changes around 12 GPa, where a
new superconducting phase of SC II appears. This suggests a possible tetragonal
to collapsed tetragonal phase transition. X-ray emission spectroscopy data also
shows the change in the electronic structure around 12 GPa. These results can be
explained by the scenario that the two SC domes under pressure originate from the
change of Fermi surface topology. Our results here show the pronounced increase
of the density of states near the Fermi surface under pressure with a structural
phase transition, which can help address our fundamental understanding for the
appearance of the SC II phase.
PMID- 27499372
TI - Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm.
AB - Abdominal aortic aneurysm (AAA) is a vascular disease involving the gradual
dilation of the abdominal aorta. It has been reported that development of AAA is
associated with inflammation of the vascular wall; however, the mechanism of AAA
rupture is not fully understood. In this study, we investigated the mechanism
underlying AAA rupture using a hypoperfusion-induced animal model. We found that
the administration of triolein increased the AAA rupture rate in the animal model
and that the number of adipocytes was increased in ruptured vascular walls
compared to non-ruptured walls. In the ruptured group, macrophage infiltration
and the protein levels of matrix metalloproteinases 2 and 9 were increased in the
areas around adipocytes, while collagen-positive areas were decreased in the
areas with adipocytes compared to those without adipocytes. The administration of
fish oil, which suppresses adipocyte hypertrophy, decreased the number and size
of adipocytes, as well as decreased the risk of AAA rupture ratio by 0.23
compared to the triolein administered group. In human AAA samples, the amount of
triglyceride in the adventitia was correlated with the diameter of the AAA. These
results suggest that AAA rupture is related to the abnormal appearance of
adipocytes in the vascular wall.
PMID- 27499374
TI - Effects of adult day care services on disability in older persons: Evaluation of
a designed service package in Iran.
AB - OBJECTIVE: To assess the effects of a rehabilitation service package designed by
the State Welfare Organization of Iran for adult day care centres on the
disability of older clients. METHODS: A case-control study, with 46 older
participants in the case group and 46 participants, matched for level of
disability, in a control group. The World Health Organization Disability
Assessment Schedule 2 was used to collect data at 4 time-points: baseline and 2,
4, and 6 months later. Data were analysed using repeated-measures analysis of
variation. RESULTS: The rehabilitation service package had significant effects on
the disability scores of older users of day care services. The disability scores
significantly changed within the subjects (p = 0.010) and between the 2 groups (p
< 0.001). Within-subjects effects in all 6 domains ("understanding and
communication" (p = 0.002), "getting around" (p = 0.046), "self-care" (p <
0.001), "getting along with people" (p < 0.001), "life activity" (p < 0.001) and
"participation" (p < 0.001)) and between-subjects effects, in all except the
"self-care" domain, showed significant differences during the 6-month study
period (p = 0.003, p < 0.001, p <0.001, p < 0.001, and p < 0.001, respectively).
CONCLUSION: The adult day care service package may have a positive role in
decreasing measures of disability among older persons over a 6-month period.
PMID- 27499375
TI - Disorder engineering and conductivity dome in ReS2 with electrolyte gating.
AB - Atomically thin rhenium disulphide (ReS2) is a member of the transition metal
dichalcogenide family of materials. This two-dimensional semiconductor is
characterized by weak interlayer coupling and a distorted 1T structure, which
leads to anisotropy in electrical and optical properties. Here we report on the
electrical transport study of mono- and multilayer ReS2 with polymer electrolyte
gating. We find that the conductivity of monolayer ReS2 is completely suppressed
at high carrier densities, an unusual feature unique to monolayers, making ReS2
the first example of such a material. Using dual-gated devices, we can
distinguish the gate-induced doping from the electrostatic disorder induced by
the polymer electrolyte itself. Theoretical calculations and a transport model
indicate that the observed conductivity suppression can be explained by a
combination of a narrow conduction band and Anderson localization due to
electrolyte-induced disorder.
PMID- 27499376
TI - Structural origin of proton mobility in a protic ionic liquid/imidazole mixture:
insights from computational and experimental results.
AB - The structure, dynamics, and phase behavior of a binary mixture based on the
protic ionic liquid 1-ethylimidazolium bis(trifluoromethanesulfonyl)imide
(C2HImTFSI) and imidazole are investigated by (1)H NMR spectroscopy, vibrational
spectroscopy, diffusion NMR, calorimetric measurements, and molecular dynamics
simulations. Particular attention is given to the nature of the H-bonds
established and the consequent occurrence of the Grotthuss mechanism of proton
transfer. We find that due to their structural similarity, the imidazolium cation
and the imidazole molecule behave as interchangeable and competing sites of
interaction for the TFSI anion. All investigated properties, that is the phase
behavior, strength of ion-ion and ion-imidazole interactions, number of specific
H-bonds, density, and self-diffusivity, are composition dependent and show trend
changes at mole fractions of imidazole (chi) approximately equal to 0.2 and 0.5.
Beyond chi = 0.8 imidazole is not miscible in C2HImTFSI at room temperature. We
find that at the equimolar composition (chi ~ 0.5) a structural transition occurs
from an ionic network mainly stabilized by coulombic forces to a mixed phase held
together by site specific H-bonds. The same composition also marks a steeper
decrease in density and increase in diffusivity, resulting from the preference of
imidazole molecules to H-bond to each other in a chain-like manner. As a result
of these structural features the Grotthuss mechanism of proton transfer is less
favored at the equimolar composition where H-bonds are too stable. By contrast,
the Grotthuss mechanism is more pronounced in the low concentration range where
imidazole acts as a base pulling the proton of the imidazolium cation. At high
imidazole concentrations the contribution from the vehicular mechanism dominates.
PMID- 27499377
TI - Composite End Points in Acute Heart Failure Research: Data Simulations Illustrate
the Limitations.
AB - Composite end points are frequently used in clinical trials of investigational
treatments for acute heart failure, eg, to boost statistical power and reduce the
overall sample size. By incorporating multiple and varying types of clinical
outcomes they provide a test for the overall efficacy of the treatment. Our
objective is to compare the performance of popular composite end points in terms
of statistical power and describe the uncertainty in these power estimates and
issues concerning implementation. We consider several composites that incorporate
outcomes of varying types (eg, time to event, categorical, and continuous). Data
are simulated for 5 outcomes, and the composites are derived and compared. Power
is evaluated graphically while varying the size of the treatment effects, thus
describing the sensitivity of power to varying circumstances and eventualities
such as opposing effects. The average z score offered the most power, although
caution should be exercised when opposing effects are anticipated. Results
emphasize the importance of an a priori assessment of power and scientific basis
for construction, including the weighting of individual outcomes deduced from
data simulations. The interpretation of a composite should be made alongside
results from the individual components. The average z score offers the most
power, but this should be considered in the research context and is not without
its limitations.
PMID- 27499378
TI - SuPAR Predicts Cardiovascular Events and Mortality in Patients With Asymptomatic
Aortic Stenosis.
AB - BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an
inflammatory marker associated with subclinical cardiovascular damage and
cardiovascular events. Whether suPAR is of prognostic value in asymptomatic
patients with aortic stenosis (AS) remains unknown. METHODS: Plasma suPAR levels
were measured in 1503 patients with a mean age of 68 years who were recruited in
the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox regression
analysis was performed to evaluate associations between suPAR and the composite
end points of ischemic cardiovascular events (ICEs), aortic valve events (AVEs),
cardiovascular and all-cause mortality after adjusting for traditional
cardiovascular risk factors, and allocation to treatment. RESULTS: The
multivariate adjusted hazard ratio (HR) (95% confidence interval [CI]) per unit
log2 ng/mL increase in suPAR was HR, 1.5; 95% CI, 1.2-1.9; P = 0.002 for ICEs;
HR, 1.2; 95% CI, 0.9-1.5; P = 0.071) for AVEs; HR, 2.0; 95% CI, 1.2-3.3; P =
0.007) for cardiovascular mortality, and HR, 2.0; 95% CI, 1.4-2.9; P < 0.001 for
all-cause mortality. CONCLUSIONS: In patients with mild-moderate AS, suPAR is
independently associated with the incidence of ICEs, cardiovascular mortality,
and all-cause mortality.
PMID- 27499379
TI - Antibody-Dependent Cellular Cytotoxicity Activity of Effector Cells from HIV
Infected Elite and Viral Controllers.
AB - Carriage of alleles encoding certain inhibitory natural killer (NK) cell
receptor/HLA ligand KIR3DL1/HLA-B combinations is associated with protection from
HIV infection and slow time to AIDS, implicating NK cells in HIV control. NK
cells also mediate antibody-dependent cellular cytotoxicity (ADCC). ADCC has been
identified as a correlate of protection in secondary analyses of the modestly
protective RV144 Thai HIV vaccine trial. In ADCC, HIV envelope (Env)-specific
antibodies (Abs) bridge HIV-infected or gp120-coated target cells and NK cells
expressing CD16 receptors for Ab Fc domains. CD16 engagement activates NK cells
to secrete cytokines/chemokines, degranulate, deliver granzyme B (GrB) to target
cells, and cytolysis. A subset of HIV+ subjects, known as slow progressors (SPs),
maintains low-level viremia without treatment. HIV+ SPs versus progressors have
higher titers and/or a greater breadth of ADCC-competent Abs. Investigations of
the functional capacity of NK effector cells following CD16 engagement in HIV+
subjects are lacking. We used the ADCC-GranToxiLux (ADCC-GTL) assay to assess the
frequency of GrB+ (%GrB+) cells generated by effector cells from 37 HIV+ SPs and
15 progressors to gp120-coated CEM.NKr.CCR5 target cells in the presence of anti
Env Abs. Subject groups were stratified according to whether or not they carried
educating KIR3DL1/HLA-B combinations able to confer NK cells with functional
potential. No differences were observed in %GrB+ target cells generated by
effector cells from carriers of educating versus noneducating KIR3DL1/HLA-B
pairs. The absence of an effect of NK cell education on this readout may be due
to loss of the ability of educated NK cells from SPs to respond to Ab-dependent
stimulation and/or the lower frequency of KIR3DL1+ than KIR3DL1- NK cells that
coexpress CD16. That KIR/HLA genotypes have minimal impact on interindividual
differences in ADCC potency has relevance for therapeutic interventions that
target ADCC for HIV control.
PMID- 27499380
TI - Aptamer-mediated universal enzyme assay based on target-triggered DNA polymerase
activity.
AB - We herein describe an innovative method for a universal fluorescence turn-on
enzyme assay, which relies on the target enzyme-triggered DNA polymerase
activity. In the first target recognition step, the target enzyme is designed to
destabilize detection probe derived from an aptamer specific to DNA polymerase
containing the overhang sequence and the complementary blocker DNA, which
consequently leads to the recovery of DNA polymerase activity inhibited by the
detection probe. This target-triggered polymerase activity is monitored in the
second signal transduction step based on primer extension reaction coupled with
TaqMan probe. Utilizing this design principle, we have successfully detected the
activities of two model enzymes, exonuclease I and uracil DNA glycosylase with
high sensitivity and selectivity. Since this strategy is composed of separated
target recognition and signal transduction modules, it could be universally
employed for the sensitive determination of numerous different target enzymes by
simply redesigning the overhang sequence of detection probe, while keeping TaqMan
probe-based signal transduction module as a universal signaling tool.
PMID- 27499381
TI - Electrochemically reduced graphene and iridium oxide nanoparticles for inhibition
based angiotensin-converting enzyme inhibitor detection.
AB - In this work, a novel biosensor based on electrochemically reduced graphene oxide
and iridium oxide nanoparticles for the detection of angiotensin-converting
enzyme inhibitor drug, captopril, is presented. For the preparation of the
biosensor, tyrosinase is immobilized onto screen printed electrode by using 1
Ethyl-3-(3-dimethylaminopropyl)-carbodiimide and N-Hydroxysuccinimide coupling
reagents, in electrochemically reduced graphene oxide and iridium oxide
nanoparticles matrix. Biosensor response is characterized towards catechol, in
terms of graphene oxide concentration, number of cycles to reduce graphene oxide,
volume of iridium oxide nanoparticles and tyrosinase solution. The designed
biosensor is used to inhibit tyrosinase activity by Captopril, which is generally
used to treat congestive heart failure. It is an angiotensin-converting enzyme
inhibitor that operates via chelating copper at the active site of tyrosinase and
thioquinone formation. The captopril detections using both inhibition ways are
very sensitive with low limits of detection: 0.019uM and 0.008uM for chelating
copper at the active site of tyrosinase and thioquinone formation, respectively.
The proposed methods have been successfully applied in captopril determination in
spiked human serum and pharmaceutical dosage forms with acceptable recovery
values.
PMID- 27499382
TI - Investigate electrochemical immunosensor of cortisol based on gold
nanoparticles/magnetic functionalized reduced graphene oxide.
AB - A sensitively competitive electrochemical immunosensor for the detection of
cortisol was successfully developed based on gold nanoparticles and magnetic
functionalized reduced graphene oxide (AuNPs/MrGO). In order to construct the
base of the immunosensor, the MrGO was initially fabricated by chemical cross
linking and used to modify the nafion pretreated glassy carbon electrode.
Subsequently, the surface of electrode was modified by AuNPs via electrochemical
deposition. A variety of cortisol (Cor) can be firmly loaded in the AuNPs/MrGO
with large specific surface area and good bioactivity to construct the basic
electrode (Cor/AuNPs/MrGO/Nafion@GCE), which was characterized by the cyclic
voltammetry (CV) and electrochemical impedance spectroscopy (EIS), respectively.
Due to the cortisol on the surface of basic electrode and samples can
competitively combine with the cortisol antibody labelled by horseradish
peroxidase (HRP-Strept-Biotin-Ab). Finally, the detection signal of
electrochemical immunosensor (HRP-Strept-Biotin-Ab-Cor/AuNPs/MrGO/Nafion@GCE) in
the test liquid had negative correlations with the concentration of cortisol in
samples. The AuNPs/MrGO with excellent electrical conductivity being applied, the
electrochemical response of the immunosensor was immensely amplified. The
immunosensor displayed excellent analytical performance for the detection of
cortisol range from 0.1 to 1000ng/mL with a detection limit of 0.05ng/mL at
3sigma. Moreover, compared the developed immunoassay with commercially available
enzyme linked immunosorbent assay, the proposed method showed good precision,
acceptable stability and reproducibility, indicating the immunosensor could be
used for the sensitive, efficient and real-time detection of cortisol in real
samples. Therefore, the present strategy provides a novel and convenient method
for clinical determination of cortisol.
PMID- 27499383
TI - Mitochondria-based biosensors with piezometric and RELS transduction for
potassium uptake and release investigations.
AB - Dysfunctional mitochondria appear to be involved in many diseases through their
role in respiration, reactive oxygen species generation, and energy production.
To aid in the design of new biosensors based on mitochondria (MT), we have
investigated the feasibility of detecting ion fluxes through the MT-membrane K+
ion channels using piezosensors with MTs immobilized either by hydrogen bonding
or thin polypyrrole (PPy) binding film. We have demonstrated for the first time
that the mitochondria-based piezosensors are able to detect ion fluxes and thus
be utilized for drug development aimed at ion channel opener- or inhibitor
function. The quartz crystal resonator responding only to mass changes in the
lower part of the MT film, penetrated by the acoustic wave, is able to detect a
pronounced cationic dynamics in PPy-bonded MT piezosensors despite of the undoped
PPy preference for pure anion dynamics. The control experiments performed by
resonance elastic light scattering (RELS) confirmed MT swelling/shrinking, ion
dynamics, and osmotic water transfer in MTs, as well as the effects of exposure
to a drug valinomycin at sub-nanomolar concentrations.
PMID- 27499384
TI - Comment on "Heavy metals in agricultural soil of the European Union with
implications for food safety" by Toth, G., Hermann, T., Da Silva, M.R. and
Montanarella, L.
PMID- 27499386
TI - Pollution effects on biochemical pathways determined in the polychaete Hediste
diversicolor collected in three Portuguese estuaries.
AB - Biomonitoring is an important tool for the assessment of the quality and
functions of ecosystems, providing information about the pollutants present and
the direct effects that they exert on organisms. Biomonitoring relies upon the
quantification of variables that can be biochemical, genetic, morphological and
physiological changes. Such variables are designated as biomarkers, and multiple
biomarkers are usually determined simultaneously in order to have a more
integrated analysis and information about sublethal early effects of
contaminants. In this work, we quantified biomarkers, associated with oxidative
stress (glutathione-S-transferases GSTs, and catalase CAT, activities; levels of
peroxidative alterations, by the thiobarbituric acid reactive substances assay,
TBARS) and neurotoxicity (acetylcholinesterase activity, AChE) in the polychaete
Hediste diversicolor. Organisms were collected at three distinct estuaries, Ria
de Aveiro (Laranjo and Sao Jacinto), Douro River (Sao Paio, Afurada, and Ribeira
da Granja), both impacted by human activities, and Minho River (Seixas), which
has been used as a reference site. Obtained data showed the occurrence of anti
oxidant responses, in most samples from contaminated sites, which was not
followed however by the occurrence of oxidative damage in organisms from Ria de
Aveiro. None of the analyzed organisms had significant impairment of
cholinesterasic activity, suggesting the absence of a prior exposure to
neurotoxic compounds. In fact, organisms collected at Ria de Aveiro had largely
increased AChE activity, suggesting an uncommon paradoxical biological response
that is further discussed.
PMID- 27499385
TI - Association between hepatitis B co-infection and elevated liver stiffness among
HIV-infected adults in Lusaka, Zambia.
AB - OBJECTIVE: To describe liver disease epidemiology among HIV-infected individuals
in Zambia. METHODS: We recruited HIV-infected adults (>=18 years) at
antiretroviral therapy initiation at two facilities in Lusaka. Using vibration
controlled transient elastography, we assessed liver stiffness, a surrogate for
fibrosis/cirrhosis, and analysed liver stiffness measurements (LSM) according to
established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for
cirrhosis). All participants underwent standardised screening for potential
causes of liver disease including chronic hepatitis B (HBV) and C virus co
infection, herbal medicine, and alcohol use. We used multivariable logistic
regression to identify factors associated with elevated liver stiffness. RESULTS:
Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53%
female). HBV co-infection (12%) and alcohol use disorders (41%) were common and
hepatitis C virus co-infection (<1%) was rare. According to LSM, 75 (12%) had
significant fibrosis and 13 (2%) had cirrhosis. In multivariable analysis, HBV co
infection as well as male sex, increased age and WHO clinical stage 3 or 4 were
independently associated with LSM >7.0 kPa (all P < 0.05). HBV co-infection was
the only independent risk factor for LSM >11.0 kPa. Among HIV-HBV patients, those
with elevated ALT and HBV viral load were more likely to have significant liver
fibrosis than patients with normal markers of HBV activity. CONCLUSIONS: HBV co
infection was the most important risk factor for liver fibrosis and cirrhosis and
should be diagnosed early in HIV care to optimise treatment outcomes.
PMID- 27499387
TI - Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl
Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in
Normal Mice.
AB - RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against
dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in
silico and were further investigated in a proof-of-concept study in normal ICR
mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT).
The sample or sitagliptin (positive control) was orally administered by a feeding
gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam
dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve
(AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of
blood insulin, which showed significant differences compared to control (P < 0.05
or 0.001). These results suggested that RRDY and yam dioscorin might be
beneficial in glycemic control in normal mice and need further investigations in
diabetic animal models.
PMID- 27499388
TI - Registration procedure for spatial correlation of physical energy deposition of
particle irradiation and cellular response utilizing cell-fluorescent ion track
hybrid detectors.
AB - The hybrid technology cell-fluorescent ion track hybrid detector (Cell-Fit-HD)
enables the investigation of radiation-related cellular events along single ion
tracks on the subcellular scale in clinical ion beams. The Cell-Fit-HD comprises
a fluorescent nuclear track detector (FNTD, the physical compartment), a device
for individual particle detection and a substrate for viable cell-coating, i.e.
the biological compartment. To date both compartments have been imaged
sequentially in situ by confocal laser scanning microscopy (CLSM). This is yet in
conflict with a functional read-out of the Cell-Fit-HD utilizing a fast live-cell
imaging of the biological compartment with low phototoxicity on greater time
scales. The read-out of the biological from the physical compartment was
uncoupled. A read-out procedure was developed to image the cell layer by
conventional widefield microscopy whereas the FNTD was imaged by CLSM. Point
mapping registration of the confocal and widefield imaging data was performed.
Non-fluorescent crystal defects (spinels) visible in both read-outs were used as
control point pairs. The accuracy achieved was on the sub-um scale. The read-out
procedure by widefield microscopy does not impair the unique ability of spatial
correlation by the Cell-Fit-HD. The uncoupling will enlarge the application
potential of the hybrid technology significantly. The registration allows for an
ultimate correlation of microscopic physical beam parameters and cell kinetics on
greater time scales. The method reported herein will be instrumental for the
introduction of a novel generation of compact detectors facilitating
biodosimetric research towards high-throughput analysis.
PMID- 27499389
TI - Nystatin and lidocaine pastilles for the local treatment of oral mucositis.
AB - Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy
in oncology. Its treatment requires oral formulations that enhance therapy
compliance, improve administration and ensure drug effectiveness. Solid dosage
forms that act by slow dissolution, such as pastilles, are an effective
alternative to mouthwashes, for their versatility, ease of administration and
extended residence time in the oral cavity. The present work describes the
development and stability studies of an innovative formulation of nystatin and
lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical
quality testing was carried out, including disintegration and dissolution
testing, texture profile analysis, grittiness and an antifungal activity testing.
A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was
obtained, presenting suitable pharmaceutical characteristics, as a disintegration
time of 17 +/- 2 min, dissolution rate and microbiological and physicochemical
for 30 days when stored at 2-8 degrees C under light protection. Palatability
was also evaluated, being well accepted by a panel of 38 healthy volunteers. This
formulation allows an accurate drug dosing by the prescriber, while enabling the
patients to control the retention time of the drugs in the oral cavity and
consequently manage their pain treatment.
PMID- 27499391
TI - Hospital malnutrition in Latin America: A systematic review.
AB - BACKGROUND: Disease-related malnutrition is a major public health issue in both
industrialised and emerging countries. The reported prevalence in hospitalised
adults ranges from 20% to 50%. Initial reports from emerging countries suggested
a higher prevalence compared with other regions, with limited data on outcomes
and costs. METHODS: We performed a systematic literature search for articles on
disease-related malnutrition in Latin American countries published between
January 1995 and September 2014. Studies reporting data on the prevalence,
clinical outcomes, or economic costs of malnutrition in an adult (>=18 years)
inpatient population with a sample size of >=30 subjects were eligible for
inclusion. Methodological quality of the studies was assessed by two independent
reviewers using published criteria. RESULTS: We identified 1467 citations; of
these, 66 studies including 29 ,474 patients in 12 Latin American countries met
the criteria for inclusion. There was considerable variability in methodology and
in the reported prevalence of disease-related malnutrition; however, prevalence
was consistently in the range of 40%-60% at the time of admission, with several
studies reporting an increase in prevalence with increasing duration of
hospitalisation. Disease-related malnutrition was associated with an increase in
infectious and non-infectious clinical complications, length of hospital stay,
and costs. CONCLUSION: Disease-related malnutrition is a highly prevalent
condition that imposes a substantial health and economic burden on the countries
of Latin America. Further research is necessary to characterise
screening/assessment practices and identify evidence-based solutions to this
persistent and costly public health issue.
PMID- 27499392
TI - Comment on: Muscle strength gains during resistance exercise training are
attenuated with soy compared with dairy or usual protein intake in older adults:
A randomized controlled trial.
PMID- 27499390
TI - Targeted alternative splicing of TAF4: a new strategy for cell reprogramming.
AB - Reprogramming of somatic cells has become a versatile tool for biomedical
research and for regenerative medicine. In the current study, we show that
manipulating alternative splicing (AS) is a highly potent strategy to produce
cells for therapeutic applications. We demonstrate that silencing of hTAF4-TAFH
activity of TAF4 converts human facial dermal fibroblasts to melanocyte-like
(iMel) cells. iMel cells produce melanin and express microphthalmia-associated
transcription factor (MITF) and its target genes at levels comparable to normal
melanocytes. Reprogramming of melanoma cells by manipulation with hTAF4-TAFH
activity upon TAFH RNAi enforces cell differentiation towards chondrogenic
pathway, whereas ectoptic expression of TAF4 results in enhanced multipotency and
neural crest-like features in melanoma cells. In both cell states, iMels and
cancer cells, hTAF4-TAFH activity controls migration by supporting E- to N
cadherin switches. From our data, we conclude that targeted splicing of hTAF4
TAFH coordinates AS of other TFIID subunits, underscoring the role of TAF4 in
synchronised changes of Pol II complex composition essential for efficient
cellular reprogramming. Taken together, targeted AS of TAF4 provides a unique
strategy for generation of iMels and recapitulating stages of melanoma
progression.
PMID- 27499393
TI - Nutritional status of older patients with oropharyngeal dysphagia in a chronic
versus an acute clinical situation.
AB - BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent risk factor for
malnutrition (MN) in older patients and both conditions are related to poor
outcome. OBJECTIVE: To explore the nutritional status in older patients with OD
in a chronic and an acute clinical situation. DESIGN: We examined 95 older (>=70
years) patients with OD associated to chronic neurological diseases or aging, and
23 older patients with OD and acute community-acquired pneumonia (CAP) with
videofluoroscopy; and 15 older people without OD. We collected nutritional
status, measured with the Mini Nutritional Assessment (MNA(r)), anthropometric
measurements, and biochemistry and bioimpedance for body composition. Functional
status was assessed with the Barthel index. RESULTS: 1) Taking into consideration
patients with OD with chronic conditions, 51.1% presented a MNA(r) <=23.5; 16.7%,
sarcopenia and a) reduced visceral and muscular protein compartments and fat
compartment; b) muscular weakness c) intracellular water depletion, and d)
reduced body weight. Patients with OD and MNA(r) <=23 needed higher levels of
nectar viscosity for a safe swallow and had increased oropharyngeal residue at
spoon-thick viscosity. 2) Patients with OD and CAP, 69.5%, presented an MNA(r)
<=23.5 and 29.4% sarcopenia, the inflammatory response of the pneumonia adding to
the more severe depletion in visceral protein and muscular mass. CONCLUSIONS:
Prevalence of impaired nutritional status (malnutrition risk, and sarcopenia)
among older patients with OD associated with either chronic or acute conditions
is very high. In patients with OD and chronic diseases, poor nutritional status
further impairs OD with an increase in oropharyngeal residue at spoon-thick
viscosity. In the acute setting there is inflammation and an additional protein
deficiency. These findings will help develop specific products both for OD and
nutritional status in each specific clinical situation.
PMID- 27499394
TI - 2016 National Rheumatic Fever Week: The status of rheumatic heart disease in
South Africa.
AB - There is evidence of early progress in the efforts to eliminate acute rheumatic
fever (ARF) and control rheumatic heart disease (RHD) in South Africa. The
caseload of ARF and RHD in paediatric units appears to be falling in some
provinces such as Gauteng, and the mortality attributed to rheumatic heart
disease at a population level has fallen from 1.3/100 000 in 2001 to 0.7/100 000
in 2012. However, the incidence of congestive heart failure due to RHD in adults
remains high (~25/100 000/year) in Gauteng Province, and is associated with a
high case fatality rate of up to 35% in 6 months. There is a need to intensify
the application of comprehensive interventions to enhance the primary and
secondary prevention and treatment of ARF/RHD in a registry-based national
programme.
PMID- 27499395
TI - Asymptomatic rheumatic heart disease in South African schoolchildren:
Implications for addressing chronic health conditions through a school health
service.
AB - When new evidence comes to light, it compels us to contemplate the implications
of such evidence for health policy and practice. This article examines recent
research evidence on the prevalence of asymptomatic rheumatic heart disease (RHD)
in South Africa and considers the implications for the Integrated School Health
Programme (ISHP). RHD is still a major burden of disease in developing countries,
and elimination of this preventable condition ranks high among World Heart
Federation goals. If left untreated, it becomes a chronic health condition that
individuals have to cope with into their adult lives. The ISHP regards the health
needs of children with chronic health conditions, which include conditions such
as RHD, as a key service component. However, the chronic health component of the
ISHP is still poorly developed and can benefit from good evidence to guide
implementation. A recent study to ascertain the prevalence of RHD in asymptomatic
schoolchildren through mass screening affords an opportunity to reflect on
whether, and how, asymptomatic chronic health conditions in schoolchildren could
be addressed, and what the implications would be if this were done through a
school-based programme such as the ISHP.
PMID- 27499396
TI - A successful lifestyle intervention model replicated in diverse clinical
settings.
AB - Lifestyle interventions can treat metabolic syndrome and prevent type 2 diabetes
mellitus, but they remain underutilised in routine practice. In 2010, an LI model
was created in a rural primary care practice and spread with few resources to
four other rural practices. A retrospective chart review evaluated changes in
health indicators in two practice environments by following 372 participants,
mainly women (mean age 52 years). Participants had a mean body mass index of 37
kg/m2at baseline and lost an average of 12% of their initial body weight as a
result of the intervention. Among participants at the first intervention site for
whom cardiometabolic data were available, the prevalence of metabolic syndrome
decreased from 58% at baseline to 19% at follow-up. Taken as a whole, our
experience suggests that LIs are feasible and deliver meaningful results in
routine primary care practice.
PMID- 27499397
TI - Severe hypertension in pregnancy: Using dynamic checklists to save lives.
AB - Severe hypertension is a major cause of morbidity and mortality. The South
African Saving Mothers report (2011 - 2013) indicates that cerebral injury due to
severe hypertension is resulting in avoidable maternal deaths. This demands that
management of severe hypertension in pregnancy needs to be improved. A rapid
acting antihypertensive is recommended for the initial management of severe
hypertension during pregnancy. A single dose of a rapid-acting agent may be
ineffective, in which case incremental doses of the same medication or another
antihypertensive may be required for adequate blood pressure control. To ensure
that appropriate antihypertensives at the correct doses are administered, the use
of a guideline in a dynamic checklist format is advocated and discussed in this
article. It is envisaged that the use of dynamic checklists will be valuable to
all healthcare professionals providing care during pregnancy and the puerperium.
PMID- 27499398
TI - The World Health Organization's mechanisms for increasing the health sector
budget: The South African context.
AB - South Africa (SA) has limited scope for raising income taxes, and the proposed
National Health Insurance (NHI) scheme will necessitate growth in the health
sector budget. The NHI White Paper suggests five funding scenarios to meet the
expected shortfall. These scenarios are a mixture of a surcharge on taxable
income, an increase in value-added tax and a payroll tax. Five alternative
options, suggested by the World Health Organization, are interrogated as ways to
decrease the general taxation proposed in the White Paper. The five mechanisms
(corporate tax, financial transaction levy, and taxes on tobacco, alcohol and
unhealthy foods) were chosen based on their fund-raising potential and their
mandatory element. A literature review provides the information for a discussion
of the potential costs of each mechanism. Within specific assumptions, potential
budgetary contribution is compared with the requirement. First, raising corporate
tax rates could raise enough funds, but the losses due to capital flight might be
too much for the local economy to bear. Second, a levy on currency transactions
is unlikely to raise the required resources, even without a probable decrease in
the number of transactions. Third, the increase in the tax on tobacco and alcohol
would need to be very large, even assuming that consumption patterns would remain
unchanged. Lastly, a tax on unhealthy food products is a new idea and could be
explored as an option - especially as the SA Treasury has announced its future
implementation. Implementing only one of the mechanisms is unlikely to increase
available funding sufficiently, but if they are implemented together the welfare
maximising tax rate for each mechanism may be high enough to fulfil the NHI
scheme's budgetary requirement, moderating the increases in the tax burden of the
SA population.
PMID- 27499399
TI - Implications of the 2015 World Health Organization isoniazid preventive therapy
recommendations on tuberculosis prevention efforts in Namibia.
AB - The World Health Organization recently released guidelines recommending 36-month
use of isoniazid preventive therapy in adults and adolescents living with HIV in
resource-limited settings. Namibia continues to grapple with one of the highest
incidences of tuberculosis (TB) worldwide. Implementation of these guidelines
requires considerations of TB epidemiology, health infrastructure, programmatic
priorities and patient adherence. This article explores the challenges Namibia
currently faces in its fight against TB and the implications of the new
guidelines on Namibian TB prevention efforts.
PMID- 27499400
TI - Antifibrinolytic drugs for acute traumatic injury.
AB - In South Africa, trauma is a major concern, with violence and road traffic
accidents being the fifth and seventh leading causes of death, respectively.
Antifibrinolytic agents have been used in trauma and major surgery to prevent
fibrinolysis and reduce blood loss. We highlight an updated Cochrane review
investigating the effect of antifibrinolytic drugs in patients with acute
traumatic injury. The review authorsconducted comprehensive literature searches
in January 2015 with regard to all randomised controlled trials comparing
antifibrinolytic agents after acute traumatic injury. Three randomised controlled
trials, of which two (n=20 451) assessed the effect of tranexamic acid (TXA),
were included. The authors concluded that TXA safely reduces mortality in trauma
with bleeding without increasing the risk ofadverse events. TXA should be
administered as early as possible, and within 3 hours of injury. There is still
uncertainty with regard to the effect of TXA on patients with traumatic brain
injury; however, ongoing randomised controlled trials should shed more light on
this.
PMID- 27499401
TI - The microbiome in chronic inflammatory airway disease: A threatened species.
AB - The human body is exposed to a multitude of microbes and infectious organisms
throughout life. Many of these organisms colonise the skin, gastrointestinal
tract (GIT) and airway. We now recognise that this colonisation includes the
lower airway, previously thought to be sterile. These colonising organisms play
an important role in disease prevention, including an array of chronic
inflammatory conditions that are unrelated to infectious diseases. However, new
evidence of immune dysregulation suggests that early colonisation, especially of
the GITand airway, by pathogenic micro-organisms, has deleterious effects that
may contribute to the potential to induce chronic inflammation in young children,
which may only express itself in adult life.
PMID- 27499402
TI - Intravenous glutathione for skin lightening: Inadequate safety data.
AB - BACKGROUND: Glutathione (GSH) is the most abundant naturally occurring non
protein thiol that protects mammalian cells from oxidative stress. Intravenous
(IV) GSH for skin lightening is advertised by clinics in South Africa and
internationally online, yet to date no published review on the subject exists.
Methods. We conducted a MEDLINE search (to 30 September 2015) of GSH use for skin
lightening and of all indications in medicine, to evaluate its safety. Results.
Two controlled clinical trials (GSH capsules: 60 patients; 2% glutathione
disulphide lotion: 30 patients) and a case series (GSH lozenges: 30 patients)
reported a significantly decreased melanin index. A case series (GSH soap: 15
patients) reported skin lightening based on photography. Two systematic reviews
of IV GSH for preventing chemo-induced toxicity and a third review of adjuvant
therapy for Parkinson's disease altogether included 10 trials. Most trials
reported either no or minimal GSH adverse effects, but all had treatment
durations of a few doses (IV) or 4 -12 weeks. No study reported long-term IV GSH
use. Conclusion. In spite of widespread reported use, there are no studies of IV
GSH use for skin lightening or of its safety for chronic use (for any
indication). The switch from brown to red melanin production may increase the
risk of sun-induced skin cancers in previously protected individuals. Regulatory
assessment of systemic GSH administration for cosmetic use by the Medicines
Control Council seems urgently warranted to protect consumers from potential side
effects and from complications of IV infusions. This is especially concerning
because of reports of GSH bought online. Effective topical GSH may be useful for
hyperpigmented skin disorders, but this requires scientific scrutiny. The debate
on the merits of cosmetic skin lightening is best handled by multidisciplinary
teams.
PMID- 27499403
TI - When may doctors give nurses telephonic treatment instructions?
AB - Doctors are expected to examine their patients before issuing telephonic
instructions to nurses. However, in emergencies or when they are aware of the
health status of their patients, it may be justified for a doctor to issue
telephonic instructions to nurses without examining the patient. Doctors on call
owe a special duty to patients, who they may have to examine or arrange for
another doctor to do so before issuing telephonic instructions. In deciding
whether doctors acted reasonably in issuing telephonic instructions to nurses,
the courts will decide whether they exercised the same degree of skill and care
as reasonably competent practitioners in their branch of the profession.
Suggestions are made concerning doctors giving telephonic instructions to nurses
regarding patients they have not examined.
PMID- 27499404
TI - Cardiogenic shock: A look at acute functional mitral incompetence.
AB - A 44-year-old man presented with cardiogenic shock secondary to acute functional
mitral incompetence as well as septic shock related to pneumonia. The patient
deteriorated haemodynamically despite adequate medical therapy. An echocardiogram
revealed a massive mitral incompetence and an ejection fraction of 32%. An intra
aortic balloon pump was placed and the patient improved dramatically. On day 6
after admission the echocardiogram was repeated, revealing a mild mitral
incompetence and an ejection fraction of 58%.
PMID- 27499405
TI - Clinical awareness for health care professionals: Fatal encephalopathy
complicating persistent vomiting in pregnancy.
AB - Women with persistent vomiting during pregnancy need early referral to
appropriate health facilities. Delayed referral and inappropriate management may
lead to metabolic encephalopathy from a variety of causes, including electrolyte
derangements or thiamine deficiency (Wernicke's encephalopathy) (WE). We present
a case of persistent vomiting in pregnancy in which there was delayed referral,
inappropriate treatment and failure to associate neurological signs such as
terminal neck stiffness with WE, resulting in poor fetomaternal outcomes. In this
report, we discuss the following lessons: (i) the need for early transfer of a
patient with persistent vomiting and enigmatic clinical features to a higher
healthcare facility; (ii) failure to associate neurological signs with
complications of hyperemesis gravidarum/WE; (iii) lack of thiamine
supplementation; and (iv) the advantages of magnetic resonance imaging over a
computed tomography scan in the diagnosis of WE.
PMID- 27499406
TI - A case of renal cell carcinoma and angiomyolipoma in an adolescent girl.
AB - We describe a case of renal cell carcinoma in the right kidney together with an
angiomyolipoma in the left kidney, encountered in an adolescent girl at
Potchefstroom Provincial Hospital, North West Province, South Africa.
PMID- 27499407
TI - Evaluation and management of patients referred to a tertiary-level hypertension
clinic in Cape Town, South Africa.
AB - BACKGROUND: Hypertension remains a global health burden, with a high incidence of
long-term morbidity and mortality. OBJECTIVE: To evaluate blood pressure (BP)
control, factors associated with poor BP control, target organ damage (TOD),
white-coat hypertension, treatment-resistant hypertension and secondary
hypertension in patients referred to a tertiary-level hypertension clinic.
METHOD: This was a prospective case-control study of patients referred for
specialist hypertension management. Patient parameters recorded included age,
gender, body mass index, uric acid, cholesterol, screening BP, follow-up BP, TOD
and medications. We also recorded causes of secondary hypertension. Net BP change
and the percentage achieving target BP were calculated in all patients followed
up. RESULTS: A total of 175 patients were sampled (72 males and 103 females, mean
age 46.5 years). Of the patients 16.6% had a normal screening BP; 62.9% of
patients were followed up, and 43.6% of these achieved BP control. After
intervention, there was a net drop of 13.2 mmHg (range 7.9 - 18.4) in systolic BP
and of 3.8 mmHg (4.4 - 12.0) in diastolic BP. Of all the patients, 12.6% had
resistant hypertension, 49.1% had evidence of left ventricular hypertrophy and
18.3% had microalbuminuria; 13.1% of the patients were diagnosed with secondary
hypertension. CONCLUSION: Specialist intervention was useful in identifying
patients with white-coat and secondary hypertension, as well as in improving
hypertension control in patients with apparent treatment-resistant hypertension.
However, a significant percentage of patients did not reach target BP, and
further efforts are required to identify the underlying causes for this.
PMID- 27499408
TI - Pan computed tomography for blunt polytrauma: Are we doing too many?
AB - BACKGROUND: Pan computed tomography (CT) is widely used in the evaluation of
patients with blunt polytrauma, but there is growing concern about the radiation
risks imposed. OBJECTIVE: To ascertain whether we were possibly overutilising pan
CT in our trauma service, and whether we could safely cut down on scans without
missing significant injuries. METHODS: We audited all pan scans performed in the
Metropolitan Trauma Service, Pietermaritzburg, South Africa, during the 12-month
period 1 January - 31 December 2012. An analysis was done to determine what
injuries were identified and how these findings influenced our management.
RESULTS: Of the 140 pan scans, 108 (77.1%) influenced management. These included
the following components: 62 brain scans (44.3%), 16 cervical spine scans
(11.4%), 50 chest scans (35.7%) and 31 abdominal scans (22.1%). The remaining 32
pan scans (22.9%) did not influence management. However, it turned out that many
of these 'clinically negative' scans were in fact clinically important, ruling
out injury in patients in whom clinical assessment was regarded as unreliable: 3
patients (2.1%) were hypoxic and had to be sedated, intubated and ventilated; 14
(10.0%) had a Glasgow Coma Score (GCS) of <15; and 9 (6.4%) had major distracting
injuries. This left only 6 pan scans (4.3%) that were not regarded as clinically
helpful. CONCLUSION: In our setting, the majority of pan scans influence
management. By ruling out significant injuries, clinically negative scans are
valuable in patients who are obtunded, intubated and ventilated, or have major
distracting injuries. In patients with a GCS of 15, not sedated and ventilated
and with no major distracting injuries, clinical assessment and alternative
imaging modalities may suffice.
PMID- 27499409
TI - South African healthcare provider perspectives on transitioning adolescents into
adult HIV care.
AB - BACKGROUND: The first generation of South African (SA) children perinatally
infected with HIV is entering adulthood, and there is now a pressing need for
systematised transfer of these patients from paediatric to adult care.
OBJECTIVES: Previous research has investigated the HIV healthcare transition in
North America and Europe, yet none has been conducted in SA. Our study is the
first to describe the perspectives of healthcare providers overseeing the
transition in resource-limited settings. METHODS: We approached healthcare
providers working in government paediatric HIV clinics and hospitals in the
Western Cape Province, SA. Seven physicians and counsellors in
adolescent/paediatric care, representing five clinics, were interviewed, and 43
completed a written survey. Interviews addressed the current state of the
transition, barriers and facilitators, and model components. Interviews were
assessed for major themes using framework analysis, while logistic regression was
applied to survey responses to identify associations with measured covariates.
RESULTS: Analysis of interview transcripts revealed several overarching
perspectives that were corroborated by survey responses. One barrier identified
was the healthcare providers' difficulty in letting go of their relationships
with the adolescent patients. Since healthcare providers regarded their patients
as particularly vulnerable, they felt a strong and protective attachment towards
them. A second barrier identified was a lack of structure and effective
communication between adult and paediatric providers; accordingly, healthcare
providers feared that they were transferring their adolescents unprepared, to a
judgemental, depersonalised and overburdened environment. All interviewees and a
majority of survey respondents (>80%) agreed that the formation of adolescent
support groups in adult care clinics as well as a later transition age would
improve the transition process. CONCLUSION: This study highlights the need for a
systematic healthcare transition for HIV-positive adolescents cared for in the
Western Cape, while acknowledging the limitations of the current healthcare
infrastructure. Several feasible recommendations have been identified, including
forming support groups and greater involvement of adolescent healthcare providers
to facilitate the transition.
PMID- 27499410
TI - Sialendoscopic treatment of recurrent juvenile parotitis: A South African case
series.
AB - BACKGROUND: Recurrent juvenile parotitis (RJP) is a well-recognised cause of
parotitis in childhood. Sialendoscopy has been extensively used for the
investigation and treatment of many benign salivary disorders, and now offers a
minimally invasive approach to RJP. OBJECTIVES: To investigate the epidemiology
and disease profile of RJP, and review the efficacy of sialendoscopy for its
investigation and treatment. METHODS: The relevant literature on RJP was
reviewed, and a retrospective folder review was performed for all patients who
had undergone sialendoscopy for RJP at two South African (SA) hospitals between
April 2013 and September 2015. Patients' epidemiological and clinical data were
recorded, as well as the findings and outcomes of ultrasonography and
sialendoscopy. In particular, the time following treatment without any further
recurrences was recorded as a measure of success. RESULTS: Five children
underwent sialendoscopic investigation and treatment for RJP. Their demographic
and disease profiles and the results of investigations and treatments were in
keeping with published literature. No surgical complications occurred, and no
patients reported any further symptoms postoperatively, with an average follow-up
of 22 months. CONCLUSION: Although small in sample size, this is the first
reported case series in the SA literature on the use of sialendoscopy for RJP,
and the results are consistent with internationally published data. Sialendoscopy
is regarded as safe and effective for the diagnosis and management of RJP, and
should be considered for patients who remain symptomatic after conservative
management.
PMID- 27499411
TI - Salvageability of renal function following renal revascularisation in children
with Takayasu's arteritis-induced renal artery stenosis.
AB - BACKGROUND: Renal artery revascularisation procedures are usually carried out on
children with renal artery stenosis from varied causes, including Takayasu's
arteritis. Reports on the outcome of such procedures in children usually refer to
the improvement in blood pressure, with only minimal mention of effects on renal
function. OBJECTIVE: Salvageability of renal function in children who underwent
renal revascularisation for Takayasu's arteritis-induced renal artery stenosis
(TARAS) was the focus of this study. METHODS: We undertook a retrospective
analysis of children aged <=16 years with angiographically confirmed TARAS who
underwent renal artery revascularisation procedures between 1990 and 2010.
Outcomes of renal function were studied over a period of 2 years and were defined
as: (i) improvement: >20% increase in estimated glomerular filtration rate (e
GFR) from presurgery value; (ii) stabilisation: e-GFR within 20% of presurgery
value; and (iii) failure: >20% deterioration in e-GFR from presurgery value. The
GFR was estimated using the Schwartz formula. RESULTS: Twenty children (9 males
and 11 females, age range 2 - 14 years) had 27 renal artery revascularisation
procedures. Thirteen of the patients (65.0%) had bilateral renal artery stenosis.
The baseline mean e-GFR was 88.6 (standard deviation (SD) 25.4) mL/min/1.73 m2
and the mean duration of follow-up was 28.80 (SD 25.62) months. All the patients
had stable or improved renal function until the 2-year follow-up, when the
proportion decreased to 92.3% (12/13), as failure was recorded in one child.
Bilateral revascularisation was found to be significantly associated with
improvement in renal function in the early postoperative period (p=0.04).
CONCLUSION: Renal artery revascularisation procedures are successful in salvaging
renal function in children with TARAS.
PMID- 27499412
TI - Feasibility of Pulse Oximetry Pre-discharge Screening Implementation for
detecting Critical Congenital heart Lesions in newborns in a secondary level
maternity hospital in the Western Cape, South Africa: The 'POPSICLe' study.
AB - BACKGROUND: Early detection of critical congenital heart disease (CCHD) through
newborn pulse oximetry (POx) screening is an effective strategy for reducing
paediatric morbidity and mortality rates and has been adopted by much of the
developed world. OBJECTIVES: To document the feasibility of implementing pre
discharge POx screening in well babies born at Mowbray Maternity Hospital, a busy
government hospital in Cape Town, South Africa. Parent and staff acceptance was
assessed. METHODS: We conducted a prospective study of predischarge POx screening
in one postnatal ward, following informed parental consent. RESULTS: During the 4
month study period, 1 017 of 2 256 babies discharged (45.1%) were offered POx
screening and 1 001 were screened; 94.0% of tests took <3 minutes to perform,
4.3% 3 - 5 minutes and 1.7% >5 minutes. Eighteen patients needed second screens
and three required third screens. Only 3.1% protocol errors were made, all
without consequence. The vast majority (91.6%) of nursing staff reported
insufficient time to perform the study screening in addition to their daily
tasks, but ~75% felt that with a full nursing staff complement and if done
routinely (not part of a study), pre-discharge POx screening could be
successfully instituted at our facility. Over 98% of the mothers had positive
comments. Two babies failed screening and required echocardiograms; one was
diagnosed with CCHD and the other with neonatal sepsis. The sensitivity and
specificity were 50% (95% confidence interval (CI) 1.3 - 98.7%) and 99.9% (95% CI
99.4 - 100%), respectively, with a percentage correct of 99.8%. CONCLUSIONS: POx
screening was supported and accepted by staff and parents. If there are no
nursing staff shortages and if it is done routinely before discharge, not as part
of a study, we conclude that POx screening could be implemented successfully
without excessive false positives or errors, or any additional burden to
cardiology services.
PMID- 27499413
TI - Attitudes to female genital mutilation/cutting among male adolescents in Ilorin,
Nigeria.
AB - BACKGROUND: The central role of males in female reproductive health issues in
patriarchal societies makes them an important group in the eradication of female
genital mutilation/cutting (FGM/C). OBJECTIVE: To determine knowledge about and
attitudes to FGM/C among male adolescents, and their preparedness to protect
their future daughters from it. METHODS: A cross-sectional survey among male
adolescent students in Ilorin, Nigeria. Participants completed a self
administered questionnaire after consent had been obtained from them or their
parents. Statistical analysis was with SPSS version 20.0 (IBM, USA). A p-value of
<0.05 was taken as significant. RESULTS: Of 1 536 male adolescents (mean age
15.09 (standard deviation 1.84) years, range 14 - 19), 1 184 (77.1%) were aware
of FGM/C, 514 (33.5%) supported female circumcision, 362 (23.6%) would circumcise
their future daughters, 420 (27.3%) were of the opinion that FGM/C had benefits,
mostly as a necessity for womanhood (109, 7.1%), and 627 (40.8%) perceived it as
wickedness against females; 546 (35.5%) were aware of efforts to eradicate FGM/C,
and 42.2% recommended education as the most important intervention to achieve
this. CONCLUSION: Education and involvement in advocacy may transform male
adolescents into agents for eradication of FGM/C.
PMID- 27499414
TI - A clinical audit of the utilisation of red cell products in elective total hip
replacement surgery.
AB - BACKGROUND: Previous studies have documented a marked variation in transfusion
practice for total hip replacement (THR) surgery. OBJECTIVE: To audit red cell
product utilisation for THR at two Western Cape tertiary referral hospitals (HY
and HG). METHODS: The folders of 207 consecutive patients undergoing elective THR
surgery from January 2013 to December 2013 were reviewed. Information relating to
age, sex, clinical observations, indications for surgery, pre- and postoperative
haemoglobin (Hb) values, comorbidities, length of hospital stay and transfusion
history was recorded. RESULTS: The transfusion rate at HY (41.6%) was
significantly higher than that at HG (10.0%). The mean postoperative Hb in the
transfused patients at HG was 8.3 g/dL v. 9.1 g/dL at HY. Females had a
significantly higher transfusion rate (33.0%) than males (15.0%) (p<0.05), and
the mean age of transfused patients was significantly greater than that of
untransfused patients (p<0.005). Although patients with comorbidities had a
higher transfusion rate than those without, this did not reach statistical
significance. Of 120 patients with complete data, 113 (94.2%) had a blood bank
order, of which the vast majority, 102/113 (90.3%), were group-and-screen (G&S)
requests; 29/113 (25.7%) were converted to a full crossmatch. CONCLUSIONS:
Overall, the transfusion rate for both hospitals was 25.8%, which is well within
published rates. A guideline Hb trigger of 8.0 g/dL is recommended as per
published guidelines, with the caveat that the clinical judgement of the
attending clinician whether a transfusion is indicated is paramount. Causes of
preoperative anaemia should be investigated and treated. Routine cross-matching
preoperatively is unnecessary, and a G&S order is sufficient.
PMID- 27499415
TI - Targeting composite treatment of type 2 diabetes in middle-income countries.
PMID- 27499416
TI - Oxidative metabolism of koumine is mainly catalyzed by microsomal CYP3A4/3A5.
AB - 1. Gelsemium elegans Benth (Loganiaceae) is a toxic plant that can be used for
committing suicide besides alleviating pains. Its anti-inflammatory and analgesic
effect mainly come from its active ingredient, namely koumine. Koumine, an indole
alkaloid, possesses widely pharmacological effects especially inhibition of
neuropathic pain. 2. This study aimed to investigate the metabolic profile of
koumine using human liver microsomes (HLMs), selective chemical inhibitors and
recombinant human CYP isoforms. Ultra-performance liquid chromatography-high
resolution mass spectrometry (UPLC-HRMS) was used to detect and identify
metabolites. 3. Four major metabolites of koumine were found after incubation
with HLMs or individual CYP isoforms. The metabolic pathways of koumine included
demethylation, dehydrogenation, oxidation and demethyl-dehydrogenation. Chemical
inhibition study showed that the inhibitor of CYP3A4/3A5 significantly decreased
(93%) the formation of koumine metabolites. Further, CYP3A4/3A5 was shown as the
most efficient isoform in biotransformation of koumine, among a series of CYP
isoforms tested. 4. In conclusion, koumine was metabolized into four oxidative
metabolites in HLMs. And CYP3A4/3A5 was probably the main contributor to the
hepatic oxidative metabolism of koumine.
PMID- 27499417
TI - Multimaterial 4D Printing with Tailorable Shape Memory Polymers.
AB - We present a new 4D printing approach that can create high resolution (up to a
few microns), multimaterial shape memory polymer (SMP) architectures. The
approach is based on high resolution projection microstereolithography (PMUSL)
and uses a family of photo-curable methacrylate based copolymer networks. We
designed the constituents and compositions to exhibit desired thermomechanical
behavior (including rubbery modulus, glass transition temperature and failure
strain which is more than 300% and larger than any existing printable materials)
to enable controlled shape memory behavior. We used a high resolution, high
contrast digital micro display to ensure high resolution of photo-curing
methacrylate based SMPs that requires higher exposure energy than more common
acrylate based polymers. An automated material exchange process enables the
manufacture of 3D composite architectures from multiple photo-curable SMPs. In
order to understand the behavior of the 3D composite microarchitectures, we carry
out high fidelity computational simulations of their complex nonlinear, time
dependent behavior and study important design considerations including local
deformation, shape fixity and free recovery rate. Simulations are in good
agreement with experiments for a series of single and multimaterial components
and can be used to facilitate the design of SMP 3D structures.
PMID- 27499418
TI - Sustainability and prevention in occupational health and safety.
PMID- 27499419
TI - The Role of Paracetamol for Closing Patent Ductus Arteriosus. A Challenging
Alternative for Ductal Closure?
PMID- 27499420
TI - Heritability of fear of humans in urban and rural populations of a bird species.
AB - Flight initiation distance (FID), a measure of an animal's tolerance to human
disturbance and a descriptor of its fear of humans, is increasingly employed for
conservation purposes and to predict the response of species to urbanization.
However, most work devoted to understanding variability in FID has been conducted
at the population level and little is still known about inter-individual
variability in this behaviour. We estimated the heritability of FID, a factor
fundamental to understanding the strength and evolutionary consequences of
selection of particular phenotypes associated with human disturbances. We used a
population of burrowing owls (Athene cunicularia) monitored long-term and for
which FID was previously shown to be highly consistent across an individual's
lifespan. Heritability estimates varied between 0.37 and 0.80, depending on the
habitat considered (urban-rural) and method used (parent-offspring regressions or
animal models). These values are unusually high compared with those previously
reported for other behavioural traits. Although more research is needed to fully
understand the underlying causes of this resemblance between relatives, selection
pressures acting on this behaviour should be seriously considered as an important
evolutionary force in animal populations increasingly exposed to human
disturbance worldwide.
PMID- 27499421
TI - Excited-state torsional relaxation dynamics of meso-meso directly linked corrole
dimers: importance of linking position.
AB - Herein, we present a combined spectroscopic and computational study on 5,5'
linked and 10,10'-linked corrole dimers, 5CD and 10CD, respectively, to reveal
their strikingly different excited-state dynamics. The excited-state dynamics of
10CD indicate relatively small electronic interactions between the two corrole
units, which is similar to the case of the meso-meso directly linked Zn(ii)
porphyrin dimer. On the other hand, 5CD exhibits characteristic excitation
wavelength-dependent dual fluorescence. Transient absorption spectra of 10CD on
the picosecond timescale showed torsional relaxation with a time constant of 25
ps, whereas the torsional relaxation of 5CD was faster, exhibiting a time
constant of 10 ps. Quantum calculations have indicated that the eccentric dual
fluorescence and the faster torsional relaxation process of 5CD are consequences
of a large pi-orbital coefficient at the connecting 5-position, which enhances
the conjugative stabilization in the excited-state. In contrast, a small pi
orbital coefficient at the 10-position and a larger torsional barrier of 10CD
cause monomer-like characters in the excited-state.
PMID- 27499423
TI - Corrigendum to "Investigations of motor-cortex cortical plasticity following
facilitatory and inhibitory transcranial theta-burst stimulation in
schizophrenia: A proof-of-concept study" [J. Psychiatr. Res. 61 (2015 Feb) 196
204].
PMID- 27499422
TI - The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016
Statement.
AB - We developed a reporting guideline to provide authors with guidance about what
should be reported when writing a paper for publication in a scientific journal
using a particular type of research design: the single-case experimental design.
This report describes the methods used to develop the Single-Case Reporting
guideline In BEhavioural interventions (SCRIBE) 2016. As a result of 2 online
surveys and a 2-day meeting of experts, the SCRIBE 2016 checklist was developed,
which is a set of 26 items that authors need to address when writing about single
case research. This article complements the more detailed SCRIBE 2016 Explanation
and Elaboration article (Tate et al., 2016 ) that provides a rationale for each
of the items and examples of adequate reporting from the literature. Both these
resources will assist authors to prepare reports of single-case research with
clarity, completeness, accuracy, and transparency. They will also provide journal
reviewers and editors with a practical checklist against which such reports may
be critically evaluated. We recommend that the SCRIBE 2016 is used by authors
preparing manuscripts describing single-case research for publication, as well as
journal reviewers and editors who are evaluating such manuscripts. SCIENTIFIC
ABSTRACT Reporting guidelines, such as the Consolidated Standards of Reporting
Trials (CONSORT) Statement, improve the reporting of research in the medical
literature (Turner et al., 2012 ). Many such guidelines exist and the CONSORT
Extension to Nonpharmacological Trials (Boutron et al., 2008 ) provides suitable
guidance for reporting between-groups intervention studies in the behavioural
sciences. The CONSORT Extension for N-of-1 Trials (CENT 2015) was developed for
multiple crossover trials with single individuals in the medical sciences
(Shamseer et al., 2015 ; Vohra et al., 2015 ), but there is no reporting
guideline in the CONSORT tradition for single-case research used in the
behavioural sciences. We developed the Single-Case Reporting guideline In
BEhavioural interventions (SCRIBE) 2016 to meet this need. This Statement article
describes the methodology of the development of the SCRIBE 2016, along with the
outcome of 2 Delphi surveys and a consensus meeting of experts. We present the
resulting 26-item SCRIBE 2016 checklist. The article complements the more
detailed SCRIBE 2016 Explanation and Elaboration article (Tate et al., 2016 )
that provides a rationale for each of the items and examples of adequate
reporting from the literature. Both these resources will assist authors to
prepare reports of single-case research with clarity, completeness, accuracy, and
transparency. They will also provide journal reviewers and editors with a
practical checklist against which such reports may be critically evaluated.
PMID- 27499424
TI - Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin
binding protein inhibition by cyclic boronates.
AB - beta-Lactamases enable resistance to almost all beta-lactam antibiotics.
Pioneering work revealed that acyclic boronic acids can act as 'transition state
analogue' inhibitors of nucleophilic serine enzymes, including serine-beta
lactamases. Here we report biochemical and biophysical analyses revealing that
cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent
beta-lactamases by a mechanism involving mimicking of the common tetrahedral
intermediate. Cyclic boronates also potently inhibit the non-essential penicillin
binding protein PBP 5 by the same mechanism of action. The results open the way
for development of dual action inhibitors effective against both serine- and
metallo-beta-lactamases, and which could also have antimicrobial activity through
inhibition of PBPs.
PMID- 27499425
TI - Comparison of age-related changes in anti-Mullerian hormone levels and other
ovarian reserve tests between healthy fertile and infertile population.
AB - In this study, we aimed to determine whether anti-Mullerian hormone (AMH) levels
vary between fertile and infertile populations and compare them with basal
follicle-stimulating hormone (FSH) levels and antral follicle count (AFC). This
was a prospective study that included 177 primarily infertile patients who
underwent IVF treatment and 162 healthy fertile patients admitted to our clinic
for benign diseases. FSH and AMH levels and the AFC of the infertile and fertile
populations were compared between the age categories <30, 30-39 and >=40.
Correlations between AMH, basal FSH, and AFC with age were evaluated. AFC and AMH
levels did not differ between the fertile and infertile groups in all age
categories. AMH was inversely correlated with age in both the fertile and
infertile populations. However, AFC revealed a stronger correlation with age in
both the fertile and infertile populations compared with basal FSH and AMH. Age
was positively correlated with basal FSH and inversely correlated with AMH and
AFC. In conclusion, there was no significant difference between the fertile and
infertile populations in terms of AMH or AFC. The decrease in ovarian reserve in
infertile patients is directly related to age, not infertility.
PMID- 27499426
TI - Previous Gardening Experience and Gardening Enjoyment Is Related to Vegetable
Preferences and Consumption Among Low-Income Elementary School Children.
AB - OBJECTIVE: To examine if gardening experience and enjoyment are associated with
vegetable exposure, preferences, and consumption of vegetables among low-income
third-grade children. DESIGN: Cross-sectional study design, using baseline data
from the Texas! Grow! Eat! Go! STUDY: SETTING: Twenty-eight Title I elementary
schools located in different counties in Texas. PARTICIPANTS: Third-grade
students (n = 1,326, 42% Hispanic) MAIN OUTCOME MEASURES: Gardening experience,
gardening enjoyment, vegetable exposure, preference, and consumption. ANALYSIS:
Random-effects regression models, adjusted for age, sex, ethnicity, and body mass
index percentile of child, estimated means and standard errors of vegetable
consumption, exposure, and preference by levels of gardening experience and
enjoyment. Wald chi2 tests evaluated the significance of differences in means of
outcomes across levels of gardening experience and enjoyment. RESULTS: Children
with more gardening experience had greater vegetable exposure and higher
vegetable preference and consumed more vegetables compared with children who
reported less gardening experience. Those who reported that they enjoyed
gardening had the highest levels of vegetable exposure, preference, and
consumption. CONCLUSIONS AND IMPLICATIONS: Garden-based interventions can have an
important and positive effect on children's vegetable consumption by increasing
exposure to fun gardening experiences.
PMID- 27499427
TI - Sustained remission after long-term biological therapy in patients with large
vessel vasculitis: an analysis of ten cases.
AB - OBJECTIVES: To describe the results obtained in clinical practice with the use of
biological therapy (BT) in patients diagnosed with Takayasu arteritis (TA) and
giant cell arteritis (GCA). METHODS: Retrospective single center study of TA/GCA
patients who received BT (infliximab [IFX], etanercept [ETN] and tocilizumab
[TCZ]). In TA, active disease was defined according to a previous National
Institutes of Health study. In GCA, active disease was defined with a modified
criteria and clinical manifestations secondary to temporal artery involvement or
polymyalgia rheumatica symptoms. Clinical data and outcomes are reported using
descriptive statistics. RESULTS: Five patients with TA and 5 with GCA were
included. The main reason for starting BT was lack of response to prior therapy
and/or >=2 relapses during GC tapering. Five patients started IFX, four TCZ and 1
ETN. Remission was observed before 6 months in all cases. Only one patient had a
relapse during long-term follow-up and the overall GC daily dose was reduced by
70%. Two AEs were considered attributable to IFX and one to TCZ. CONCLUSION: A
favorable and sustained response to BT was observed in our patients with TA and
GCA. Thus, BT might be considered as an alternative in patients with large vessel
arteritis refractory to conventional treatment or with GC related comorbidities.
PMID- 27499428
TI - Van Neck-Odelberg disease: Another cause of limp in childhood.
PMID- 27499429
TI - Methylation of the SEPT9_v2 promoter as a novel marker for the detection of
circulating tumor DNA in breast cancer patients.
AB - The aim of the present study was to evaluate the promoter methylation status of
SEPT9_v2 in breast cancer and to detect this methylated gene in circulating tumor
DNA (ctDNA) in plasma. Bisulfite sequencing was performed with a next generation
sequencer. Methylation of the SEPT9_v2 promoter was found in 67% (8/12) of breast
cancer cell lines and 53% (10/19) of breast tumor tissue, but not in normal
breast tissue (0/19). A clear inverse correlation was observed between the
expression of SEPT9_v2 mRNA and the methylation index (MI) both in cell lines and
breast cancer tissues. The MI of SEPT9_v2 was significantly higher in non-basal
subtype of breast cancer (13.0%, n=84) than in basal subtype (3.0%, n=23)
(P<0.0001). Methylated SEPT9_v2 ctDNA in plasma was detected in 11% (9/82) of
primary breast cancer patients and 52% (26/50) of metastatic breast cancer
patients, but not in the healthy controls (0/51). These results indicate that
SEPT9_v2 promoter hypermethylation, which silences the expression of SEPT9_v2
mRNA, is observed in a significant proportion of breast tumors, and that
methylated SEPT9_v2 may serve as a novel tumor marker for breast cancer.
PMID- 27499430
TI - Investigation on the neutral and anionic BxAlyH2 (x + y = 7, 8, 9) clusters using
density functional theory combined with photoelectron spectroscopy.
AB - The structure and bonding nature of neutral and negatively charged BxAlyH2 (x + y
= 7, 8, 9) clusters are investigated with the aid of previously published
experimental photoelectron spectra combined with the present density functional
theory calculations. The comparison between the experimental photoelectron
spectra and theoretical simulated spectra helps to identify the ground state
structures. The accuracy of the obtained ground state structures is further
verified by calculating their adiabatic electron affinities and vertical
detachment energies and comparing them against available experimental data. The
results show that the structures of BxAlyH2 transform from three-dimensional to
planar structures as the number of boron atoms increases. Moreover, boron atoms
tend to bind together forming Bn units. The hydrogen atoms prefer to bind with
boron atoms rather than aluminum atoms. The analyses of the molecular orbital on
the ground state structures further support the abovementioned results.
PMID- 27499431
TI - Serum uric acid change and modification of blood pressure and fasting plasma
glucose in an overall healthy population sample: data from the Brisighella heart
study.
AB - BACKGROUND: Serum uric acid (SUA) is an emerging risk factor for incident
hypertension and type 2 diabetes. It is less clear if changes in SUA are
associated to different incidence in these main cardiovascular risk factors.
METHODS: From the cohort of the Brisighella Heart Study, we selected non-diabetic
subjects that in 2008 were untreated with SUA-lowering drugs nor antihypertensive
ones. Then we divided the subjects in four main groups: the ones that maintained
their SUA level unchanged during the next 4 years, the ones that increased it >1
mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment
and the ones that reduced it >1 mg/dL with the continuous use of allopurinol.
RESULTS: Compared with 2008, SBP significantly increased in subjects with
worsened (and untreated) SUA level, while improved in subjects treated with
allopurinol (p < 0.05). In 2012, subjects with worsened (and untreated) SUA level
had a significantly higher SBP compared with subjects with unchanged SUA and
those with SUA improved after allopurinol treatment (p < 0.05). An identical
trend has been observed as it regards FPG. CONCLUSION: It seems that SUA
improvement could positively influence the age-related worsening of SBP and FPG
in general population. Key messages Serum uric acid (SUA) is an emerging risk
factor for incident hypertension and type 2 diabetes. SUA improvement could
positively influence the age-related worsening of SBP and FPG in general
population.
PMID- 27499432
TI - In vitro growth of multidrug-resistant Neisseria gonorrhoeae isolates is
inhibited by ETX0914, a novel spiropyrimidinetrione.
AB - Antimicrobial resistance in Neisseria gonorrhoeae has severely limited the number
of treatment options, and the emergence of extended-spectrum cephalosporin
resistance threatens the effectiveness of the last remaining recommended
treatment regimen. This study assessed the in vitro susceptibility of N.
gonorrhoeae to ETX0914, a novel spiropyrimidinetrione that inhibits DNA
biosynthesis. In vitro activity was determined by agar dilution against 100 N.
gonorrhoeae isolates collected from men presenting with urethritis in the USA
during 2012-2013 through the Gonococcal Isolate Surveillance Project. The minimum
inhibitory concentration (MIC) that inhibited growth in 50% (MIC50) and 90%
(MIC90) of isolates was calculated for each antimicrobial agent. ETX0914
demonstrated a high level of antimicrobial activity against N. gonorrhoeae,
including isolates with decreased susceptibility or resistance to currently
available agents. The ability of ETX0914 to inhibit the growth of N. gonorrhoeae
was similar to ceftriaxone, which is currently recommended in combination with
azithromycin to treat gonorrhoea. The data presented in this study strongly
suggest that ETX0914 should be evaluated in a clinical trial for the treatment of
N. gonorrhoeae.
PMID- 27499433
TI - HIV aspartic peptidase inhibitors are effective drugs against the trypomastigote
form of the human pathogen Trypanosoma cruzi.
AB - There is a general lack of effective and non-toxic chemotherapeutic agents
against Chagas' disease despite more than a century of research. In this regard,
we have verified the impact of human immunodeficiency virus aspartic peptidase
inhibitors (HIV-PIs) on the viability and morphology of infective trypomastigote
forms of Trypanosoma cruzi as well as on the aspartic peptidase and proteasome
activities produced by this parasite. The effects of HIV-PIs on viability were
assessed by counting motile parasites in a Neubauer chamber. Morphological
alterations were detected by light microscopy of Giemsa-stained smears and
scanning electron microscopy. Modulation of aspartic peptidase and proteasome
activities by the HIV-PIs was measured by cleavage of fluorogenic peptide
substrates. The majority of the HIV-PIs (6/9) were able to drastically decrease
the viability of trypomastigotes after 4 h of treatment, with nelfinavir and
lopinavir being the most effective compounds presenting LD50 values of 8.6 uM and
10.6 uM, respectively. Additionally, both HIV-PIs were demonstrated to be
effective in a time- and cell density-dependent manner. Treatment with nelfinavir
and lopinavir caused many morphological/ultrastructural alterations in
trypomastigotes; parasites became round in shape, with reduced cell size and
flagellar shortening. Nelfinavir and lopinavir were also capable of significantly
inhibiting the aspartic peptidase and proteasome activities measured in
trypomastigote extracts. These results strengthen the data on the positive
effects of HIV-PIs on parasitic infections, possibly by targeting the parasite
aspartic peptidase(s) and proteasome(s), opening a new possibility for the use of
these clinically approved drugs as an alternative chemotherapy to treat Chagas'
disease.
PMID- 27499434
TI - Characterisation of class 3 integrons with oxacillinase gene cassettes in
hospital sewage and sludge samples from France and Luxembourg.
AB - In this study, antibiotic resistance class 3 integrons in Gram-negative bacteria
isolated from hospital sewage and sludge and their genetic contents were
characterised. Two samples of hospital effluent from France and Luxembourg and
one sample of sludge from a wastewater treatment plant in France were collected
in 2010 and 2011. Bacteria were cultured on selective agar plates and integrons
were detected in colonies by quantitative PCR. Integron gene cassette arrays and
their genetic environments were analysed by next-generation sequencing. Three
class 3 integron-positive isolates were detected, including Acinetobacter
johnsonii LIM75 (French hospital effluent), Aeromonas allosaccharophila LIM82
(sludge) and Citrobacter freundii LIM86 (Luxembourg hospital effluent). The gene
cassettes were all implicated in antibiotic (aminoglycoside and beta-lactam) or
antiseptic resistance. An oxacillinase gene cassette (blaOXA-10, blaOXA-368 or
blaOXA-2) was found in each integron. All of the class 3 integrons were located
on small mobilisable plasmids. This study highlights the role of class 3
integrons in the dissemination of clinically relevant antibiotic resistance
genes, notably oxacillinase genes, in hospital effluent.
PMID- 27499435
TI - The influence of human papillomavirus on nasopharyngeal carcinoma in Japan.
AB - OBJECTIVE: Although Japan is a non-endemic area with nasopharyngeal carcinoma
(NPC), the proportion of WHO type I NPC in Japan are different from that in non
endemic areas such as North America and Europe. Recently, it is said that not
only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an
influence on NPC in non-endemic areas. The aim of this study is to clarify the
influence of HPV on NPC in Japan. METHODS: Paraffin-embedded tumor specimens were
available for 59 patients with NPC diagnosed between 1996 and 2015. We detected
the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization
for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to
compare the overall survival by viral status. RESULTS: Among the 59 patients, 49
(83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and
8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected
with EBV. There were no significant differences between the overall survival in
the three groups (p=0.111). CONCLUSION: In Japan, HPV was detected in a few
patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis
in this population.
PMID- 27499436
TI - New inflammatory parameters in laryngopharyngeal reflux.
AB - OBJECTIVES: To investigate new inflammatory markers in patients with
laryngopharyngeal reflux and determine whether these inflammatory parameters
change in response to laryngopharyngeal reflux treatment. METHODS: Complete blood
count was evaluated to obtain platelet count and mean platelet volume and
calculate neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio.
Laryngopharyngeal reflux patients underwent three-month lansoprazole treatment.
RESULTS: The study included 45 laryngopharyngeal reflux patients (9 men (20 per
cent); mean age, 37.4 +/- 11.6 years) and 35 healthy age- and sex-matched
controls (7 men (20 per cent); mean age, 38.6 +/- 8.9 years). The study group had
significantly higher platelet-to-lymphocyte ratios and lower mean platelet
volumes than the control group (p = 0.004 and p = 0.047, respectively). There was
a significant correlation between platelet-to-lymphocyte ratios and initial
inflammatory symptoms (reflux symptom index, p = 0.025; reflux finding score, p =
0.013). There was also a significant correlation between mean platelet volume
increase and symptom resolution in the first and third months of treatment (p =
0.04 and p = 0.03, respectively). CONCLUSION: Platelet-to-lymphocyte ratio, a new
inflammatory marker of chronic inflammation, was significantly higher in
laryngopharyngeal reflux patients. Moreover, these patients had significantly
lower mean platelet volume values, which increased with post-treatment symptom
improvement.
PMID- 27499437
TI - CCL22 and IL-37 inhibit the proliferation and epithelial-mesenchymal transition
process of NSCLC A549 cells.
AB - In the present study, we aimed to investigate the effects of CC chemokine ligand
22 (CCL22) and interleukin-37 (IL-37) on the proliferation and epithelial
mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) A549 cells.
pDsRed-CCL22 and pEGFP-IL-37 plasmids were constructed. A549 cells were divided
into six groups: the control, the pDsRed-N1 blank plasmid, the pEGFP-C1 blank
plasmid, the pDsRed-CCL22 plasmid, the pEGFP-IL-37 plasmid and the pDsRed-CCL22 +
pEGFP-IL-37 plasmid group. Expression levels and localization of CCL22 and IL-37
in cells were detected by confocal microscopy. Phase-contrast microscopy was
applied for observing cellular morphology. Real-time fluorescence quantitative
polymerase chain reaction (RT-qPCR) was used for detecting the mRNA levels of
vimentin, N-cadherin and E-cadherin, and their protein expression levels were
tested using western blotting. Constructed plasmids expressed CCL22 and IL-37,
both of which had a co-localization in the cell membrane. MTT assay and cell
observation results revealed that CCL22 and IL-37 inhibited the proliferation and
EMT process of the A549 cells. The results of RT-qPCR and western blotting
revealed that decreased vimentin and N-cadherin mRNA and protein expression
levels, and increased E-cadherin mRNA and protein expression levels were found in
the pDsRed-CCL22 plasmid, pEGFP-IL-37 plasmid and pDsRed-CCL22 + pEGFP-IL-37
plasmid groups when compared with the control, the pDsRed-N1 blank plasmid and
the pEGFP-C1 blank plasmid groups (all P<0.05), and decreased vimentin and N
cadherin mRNA and protein expression levels and increased E-cadherin mRNA and
protein expression levels were found in the pDsRed-CCL22 + pEGFP-IL-37 plasmid
group when compared with the pDsRed-CCL22 plasmid and the pEGFP-IL-37 plasmid
groups (all P<0.05). CCL22 and IL-37 with a co-localization in the A549 cells
inhibited the proliferation and EMT process in A549 cells. The antitumor effects
of CCL22 and IL37 provide a strategy for the treatment of NSCLC.
PMID- 27499438
TI - Structural Basis for a New Templated Activity by Terminal Deoxynucleotidyl
Transferase: Implications for V(D)J Recombination.
AB - Eukaryotic DNA polymerase of the polX family, such as pol MU and terminal
deoxynucleotidyl transferase (TdT), are key components of the non-homologous end
joining or V(D)J recombination machinery, respectively. The established role of
TdT is to add random nucleotides during V(D)J recombination. Here we show that
TdT also has a templated-polymerase activity, similar to pol MU, in the presence
of higher concentrations of a downstream DNA duplex, and performs a micro
homology single base-pair search to align the DNA synapsis. To understand the
molecular basis of this alignment, we solve crystal structures of TdT with four
DNA strands and study the influence of the 3' protruding end. Two mutations in
TdT inspired by sequence alignments with pol MU further improve the templated
activity. We propose that both templated and untemplated activities of TdT are
needed to explain the distributions of lengths of N regions observed
experimentally in T cell receptors and antibodies.
PMID- 27499439
TI - Tankyrase Sterile alpha Motif Domain Polymerization Is Required for Its Role in
Wnt Signaling.
AB - Tankyrase-1 (TNKS1/PARP-5a) is a poly(ADP-ribose) polymerase (PARP) enzyme that
regulates multiple cellular processes creating a poly(ADP-ribose)
posttranslational modification that can lead to target protein turnover. TNKS1
thereby controls protein levels of key components of signaling pathways,
including Axin1, the limiting component of the destruction complex in canonical
Wnt signaling that degrades beta-catenin to prevent its coactivator function in
gene expression. There are limited molecular level insights into TNKS1 regulation
in cell signaling pathways. TNKS1 has a sterile alpha motif (SAM) domain that is
known to mediate polymerization, but the functional requirement for SAM
polymerization has not been assessed. We have determined the crystal structure of
wild-type human TNKS1 SAM domain and used structure-based mutagenesis to disrupt
polymer formation and assess the consequences on TNKS1 regulation of beta-catenin
dependent transcription. Our data indicate the SAM polymer is critical for TNKS1
catalytic activity and allows TNKS1 to efficiently access cytoplasmic signaling
complexes.
PMID- 27499440
TI - Structural Basis for Receptor Recognition by the Human CD59-Responsive
Cholesterol-Dependent Cytolysins.
AB - Cholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that
punch holes in the outer membrane of eukaryotic cells. Cholesterol serves as the
receptor, but a subclass of CDCs first binds to human CD59. Here we describe the
crystal structures of vaginolysin and intermedilysin complexed to CD59. These
studies, together with small-angle X-ray scattering, reveal that CD59 binds to
each at different, though overlapping, sites, consistent with molecular dynamics
simulations and binding studies. The CDC consensus undecapeptide motif, which for
the CD59-responsive CDCs has a proline instead of a tryptophan in the motif,
adopts a strikingly different conformation between the structures; our data
suggest that the proline acts as a selectivity switch to ensure CD59-dependent
CDCs bind their protein receptor first in preference to cholesterol. The
structural data suggest a detailed model of how these water-soluble toxins
assemble as prepores on the cell surface.
PMID- 27499442
TI - The Dynamic Basis for Signal Propagation in Human Pin1-WW.
AB - Allostery is the structural manifestation of information transduction in
biomolecules. Its hallmark is conformational change induced by perturbations at a
distal site. An increasing body of evidence demonstrates the presence of
allostery in very flexible and even disordered proteins, encouraging a
thermodynamic description of this phenomenon. Still, resolving such processes at
atomic resolution is difficult. Here we establish a protocol to determine
atomistic thermodynamic models of such systems using high-resolution solution
state nuclear magnetic resonance data and extensive molecular simulations. Using
this methodology, we study information transduction in the WW domain of a key
cell-cycle regulator Pin1. Pin1 binds promiscuously to phospho-Ser/Thr-Pro
motifs, however, disparate structural and dynamic responses have been reported
upon binding different ligands. Our model consists of two topologically distinct
states whose relative population may be specifically skewed by an incoming
ligand. This model provides a canonical basis for the understanding of multi
functionality in Pin1.
PMID- 27499441
TI - Structural Basis for the Recognition of Eukaryotic Elongation Factor 2 Kinase by
Calmodulin.
AB - Binding of Ca(2+)-loaded calmodulin (CaM) activates eukaryotic elongation factor
2 kinase (eEF-2K) that phosphorylates eEF-2, its only known cellular target,
leading to a decrease in global protein synthesis. Here, using an eEF-2K-derived
peptide (eEF-2KCBD) that encodes the region necessary for its CaM-mediated
activation, we provide a structural basis for their interaction. The striking
feature of this association is the absence of Ca(2+) from the CaM C-lobe sites,
even under high Ca(2+) conditions. eEF-2KCBD engages CaM largely through the C
lobe of the latter in an anti-parallel 1-5-8 hydrophobic mode reinforced by a
pair of unique electrostatic contacts. Sparse interactions of eEF-2KCBD with the
CaM N lobe results in persisting inter-lobe mobility. A conserved eEF-2K residue
(W85) anchors it to CaM by inserting into a deep hydrophobic cavity within the
CaM C lobe. Mutation of this residue (W85S) substantially weakens interactions
between full-length eEF-2K and CaM in vitro and reduces eEF-2 phosphorylation in
cells.
PMID- 27499443
TI - Chimneys and sandwiches for endovascular arch repair in patients with Marfan
syndrome: Are we snorkeling in cloudy waters?
PMID- 27499444
TI - Bioprosthetic leaflet perforation associated with suture tails.
PMID- 27499445
TI - Phenolic profile and antioxidant activity from non-toxic Mexican Jatropha curcas
L. shell methanolic extracts.
AB - Jatropha curcas seed shells are the by-product obtained during oil extraction
process. Recently, its chemical composition has gained attention since its
potential applications. The aim of this study was to identify phenolic compounds
profile from a non-toxic J. curcas shell from Mexico, besides, evaluate J. curcas
shell methanolic extract (JcSME) antioxidant activity. Free, conjugate and bound
phenolics were fractionated and quantified (606.7, 193.32 and 909.59 MUg/g shell,
respectively) and 13 individual phenolic compounds were detected by HPLC. The
radical-scavenging activity of JcSME was similar to Trolox and ascorbic acid by
DPPH assay while by ABTS assay it was similar to BHT. Effective antioxidant
capacity by ORAC was found (426.44 +/- 53.39 MUmol Trolox equivalents/g shell).
The Mexican non-toxic J. curcas shell is rich in phenolic compounds with high
antioxidant activity; hence, it could be considerate as a good source of natural
antioxidants.
PMID- 27499446
TI - Unified Electromagnetic-Electronic Design of Light Trapping Silicon Solar Cells.
AB - A three-dimensional unified electromagnetic-electronic model is developed in
conjunction with a light trapping scheme in order to predict and maximize
combined electron-photon harvesting in ultrathin crystalline silicon solar cells.
The comparison between a bare and light trapping cell shows significant
enhancement in photon absorption and electron collection. The model further
demonstrates that in order to achieve high energy conversion efficiency, charge
separation must be optimized through control of the doping profile and surface
passivation. Despite having a larger number of surface defect states caused by
the surface patterning in light trapping cells, we show that the higher charge
carrier generation and collection in this design compensates the absorption and
recombination losses and ultimately results in an increase in energy conversion
efficiency. The fundamental physics behind this specific design approach is
validated through its application to a 3 MUm thick functional light trapping
solar cell which shows 192% efficiency enhancement with respect to the bare cell
of same thickness. Such a unified design approach will pave the path towards
achieving the well-known Shockley-Queisser (SQ) limit for c-Si in thin-film (<30
MUm) geometries.
PMID- 27499447
TI - Biphasic influence of PGE2 on the resorption activity of osteoclast-like cells
derived from human peripheral blood monocytes and mouse RAW264.7 cells.
AB - Osteoclasts are large bone-resorbing cells of hematopoietic origin. Their main
function is to dissolve the inorganic component hydroxyapatite and to degrade the
organic bone matrix. Prostaglandin E2 (PGE2) indirectly affects osteoclasts by
stimulating osteoblasts to release factors that influence osteoclast activity.
The direct effect of PGE2 on osteoclasts is still controversial. To study the
influence of PGE2 on osteoclast activity, human peripheral blood monocytes
(hPBMC) and mouse RAW264.7 cells were cultured on osteoblast-derived
extracellular matrix. hPBMC and RAW264.7 cells were differentiated by the
addition of macrophage colony-stimulation factor and receptor activator of
NFkappaB ligand and treated with PGE2 before and after differentiation induction.
The pit area, an indicator of resorption activity, and the activity of tartrate
resistant acid phosphatase were dose-dependently inhibited when PGE2 was present
ab initio, whereas the resorption activity remained unchanged when the cells were
exposed to PGE2 from day 4 of culture. These results lead to the conclusion that
PGE2 treatment inhibits only the differentiation of precursor osteoclasts whereas
differentiated osteoclasts are not affected.
PMID- 27499448
TI - Docosahexaenoic acid supplementation (DHA) and the return on investment for
pregnancy outcomes.
AB - The Kansas University DHA Outcomes Study (KUDOS) found a significant reduction in
early preterm births with a supplement of 600mg DHA per day compared to placebo.
The objective of this analysis was to determine if hospital costs differed
between groups. We applied a post-hoc cost analysis of the delivery
hospitalization and all hospitalizations in the following year to 197 mother
infant dyads who delivered at Kansas University Hospital. Hospital cost saving of
DHA supplementation amounted to $1678 per infant. Even after adjusting for the
estimated cost of providing 600mg/d DHA for 26 weeks ($166.48) and a slightly
higher maternal care cost ($26) in the DHA group, the net saving per dyad was
$1484. Extrapolating this to the nearly 4 million US deliveries per year suggests
universal supplementation with 600mg/d during the last 2 trimesters of pregnancy
could save the US health care system up to USD 6 billion.
PMID- 27499449
TI - Comparison of the effects of EPA and DHA alone or in combination in a murine
model of myocardial infarction.
AB - The aim of this project was to investigate the impact of two dietary omega-3
polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA), alone or in combination, on infarct size. Adult, male
Sprague-Dawley rats were fed for 14 days with different omega-3 diets. The
animals were subjected to ischemia for 40min followed by reperfusion. Infarct
size, Akt (protein kinase B) activation level, caspase-3 activity and
mitochondrial permeability transition pore (mPTP) opening were measured. The
results indicate that EPA or DHA alone significantly reduced infarct size
compared to the other diets. Akt activity was increased in the group fed EPA or
DHA alone, whereas no significant activation was observed in the other groups
compared to no omega-3 PUFA. DHA alone reduced caspase-3 activity and conferred
resistance to mPTP opening. In conclusion, our results demonstrate that EPA and
DHA are individually effective in diminishing infarct size in our experimental
model while their combination is not.
PMID- 27499451
TI - Dissimilatory Nitrate Reduction Processes in Typical Chinese Paddy Soils: Rates,
Relative Contributions, and Influencing Factors.
AB - Using soil slurry-based (15)N tracer combined with N2/Ar technique, the potential
rates of denitrification, anaerobic ammonium oxidation (anammox), and
dissimilatory nitrate reduction to ammonium (DNRA), and their respective
contributions to total nitrate reduction were investigated in 11 typical paddy
soils across China. The measured rates of denitrification, anammox, and DNRA
varied from 2.37 to 8.31 nmol N g(-1) h(-1), 0.15 to 0.77 nmol N g(-1) h(-1) and
0.03 to 0.54 nmol N g(-1) h(-1), respectively. The denitrification and anammox
rates were significantly correlated with the soil organic carbon content, nitrate
concentration, and the abundance of nosZ genes. The DNRA rates were significantly
correlated with the soil C/N, extractable organic carbon (EOC)/NO3(-) ratio, and
sulfate concentration. Denitrification was the dominant pathway (76.75-92.47%),
and anammox (4.48-9.23%) and DNRA (0.54-17.63%) also contributed substantially to
total nitrate reduction. The N loss or N conservation attributed to anammox and
DNRA was 4.06-21.24 and 0.89-15.01 g N m(-2) y(-1), respectively. This study
reports the first simultaneous investigation of the dissimilatory nitrate
reduction processes in paddy soils, highlighting that anammox and DNRA play
important roles in removing nitrate and should be considered when evaluating N
transformation processes in paddy fields.
PMID- 27499450
TI - Impact of co-payment for outpatient utilization among Medical Aid beneficiaries
in Korea: A 5-year time series study.
AB - BACKGROUND: The Korean government implemented an outpatient co-payment scheme in
July 2007 to control Medical-Aid beneficiaries' overutilization of healthcare
services. OBJECTIVES: To assess changes in the utilization of medical services
resulting from the outpatient co-payment scheme. METHODS: 410,142 subjects were
selected and health insurance reimbursement data from July 2006 to June 2011 was
examined. We assessed the changes in the total medical cost, total adjusted
patient days, inpatient days, inpatient total medical cost, the number of
outpatient visits, and outpatient total medical cost using segmented regression
analysis. RESULTS: Following the introduction of the policy, the number of
outpatient visits per person fell by 0.16 days in July 2008, and by 0.06 days in
July 2010, compared to June 2007. The outpatient total medical cost per person
rose by $4.11 in July 2010 compared to June 2007. The inpatient utilization
increased constantly during the period of the study. So the total medical cost as
well as the total adjusted number of patient days also increased constantly.
CONCLUSION: The outpatient co-payment policy was effective for reducing the
number of outpatient visits. It could not control the cost per outpatient visit
and inpatient utilization. So the total medical cost was increased.
PMID- 27499452
TI - Osseous Injury Associated With Ligamentous Tear of the Knee.
AB - One of the most common knee injuries is ligament tear, which may initially
manifest as an osseous injury in radiographs. Radiologists should therefore be
able to recognize ligament tears of the knee as osseous abnormalities in images.
This review focuses on the imaging features of knee ligament injuries and their
related osseous injuries: anterior cruciate ligament (ACL) tear with Segond
fracture; associated marrow contusion; ACL avulsion fracture; posterior cruciate
ligament (PCL) tear with osseous avulsion of the ligament including arcuate sign;
reverse Segond fracture; PCL avulsion fracture; medial collateral ligament tear
with Pellegrini-Stieda disease; lateral collateral ligament tear with avulsion
fracture of the fibular head; and patellar ligament injuries with Osgood
Schlatter and Sinding-Larsen-Johansson.
PMID- 27499453
TI - Isolation of three new annonaceous acetogenins from Graviola fruit (Annona
muricata) and their anti-proliferation on human prostate cancer cell PC-3.
AB - Bioassay-guided fractionation of the fruit powder of Graviola (Annona muricata)
was continued to be conducted and yielded three more novel bioactive compounds: C
35 annonaceous acetogenins, muricins M and N, and C-37 annonaceous acetogenins,
muricenin. They all contain a mono-tetrahydrofuran ring and four hydroxyl groups.
The structures were elucidated by spectral methods and chemical modification
after isolation via open column chromatographic separation and HPLC purification.
Especially, murices M and N demonstrated more potent anti-proliferative
activities against human prostate cancer PC-3 cells.
PMID- 27499454
TI - Design and evaluation of 1,7-naphthyridones as novel KDM5 inhibitors.
AB - Features from a high throughput screening (HTS) hit and a previously reported
scaffold were combined to generate 1,7-naphthyridones as novel KDM5 enzyme
inhibitors with nanomolar potencies. These molecules exhibited high selectivity
over the related KDM4C and KDM2B isoforms. An X-ray co-crystal structure of a
representative molecule bound to KDM5A showed that these inhibitors are
competitive with the co-substrate (2-oxoglutarate or 2-OG).
PMID- 27499455
TI - Discovery and structure-activity relationships of a novel isothiazolone class of
bacterial type II topoisomerase inhibitors.
AB - There is an urgent and unmet medical need for new antibacterial drugs that tackle
infections caused by multidrug-resistant (MDR) pathogens. During the course of
our wider efforts to discover and exploit novel mechanism of action
antibacterials, we have identified a novel series of isothiazolone based
inhibitors of bacterial type II topoisomerase. Compounds from the class displayed
excellent activity against both Gram-positive and Gram-negative bacteria with
encouraging activity against a panel of MDR clinical Escherichia coli isolates
when compared to ciprofloxacin. Representative compounds also displayed a
promising in vitro safety profile.
PMID- 27499457
TI - Distinct clinical characteristics and therapeutic modalities for diabetic
ketoacidosis in type 1 and type 2 diabetes mellitus.
AB - AIMS: Patients with type 1 diabetes often develop diabetic ketoacidosis (DKA).
Reportedly, DKA in type 2 diabetes has higher mortality despite its limited
occurrence. The exact clinical characteristics and therapeutic modalities
yielding successful outcomes in DKA type 2 diabetes remain unknown. METHODS: This
retrospective study compared the clinical features and detailed treatment of
consecutive type 1 and type 2 diabetes patients hospitalized with DKA between
January 2001 and December 2014. RESULTS: We report on 127 patients with type 1
and 74 patients with type 2 diabetes whose DKA was successfully treated. The most
frequent precipitating cause for DKA was infectious disease for patients with
type 1 diabetes and consumption of sugar-containing beverages for those with type
2 diabetes. Type 2 diabetes patients showed higher mean plasma glucose levels
than those with type 1 diabetes (48.4+/-21.6, vs. 37.1+/-16.4mmol/l, P<0.01) and
higher serum creatinine, blood urea nitrogen, and hemoglobin levels, which
normalized after DKA resolution. Compared with type 1 diabetes patients, those
with type 2 diabetes required distinctly higher daily total insulin dosage
(35.9+/-37.0U, vs. 20.2+/-23.3U, P<0.01), larger replacement fluid volumes
(4.17+/-2.69L, vs. 2.29+/-1.57L, P<0.01) and greater potassium supplementation
(23.9+/-36.5mEq, vs. 11.2+/-17.9mEq, P<0.01) to resolve DKA and reduce plasma
glucose level to <=16.7mmol/l. CONCLUSIONS: DKA patients with type 2 diabetes
required management with a modified treatment protocol to resolve their profound
hyperglycemia and dehydration compared with those with type 1 diabetes.
PMID- 27499456
TI - Empagliflozin in combination with oral agents in young and overweight/obese Type
2 diabetes mellitus patients: A pooled analysis of three randomized trials.
AB - AIMS: This analysis aimed to evaluate efficacy and safety of empagliflozin in
combination therapy in <65 y.o. patients, overweight/obese, and with uncontrolled
T2DM. METHODS: Pooled analysis from three phase-III trials, in <65 y.o. patients,
with BMI 25-35kg/m2, and HbA1c >=8% at baseline. Patients (N=439) were randomized
to placebo (n=138), empagliflozin 10mg (n=160), or empagliflozin 25mg (n=141)
once daily (24weeks) as add-on to metformin, to metformin plus sulfonylurea, or
to pioglitazone +/- metformin. RESULTS: At week 24, adjusted mean (SE) changes
from baseline in HbA1c were -0.19% (0.07) for placebo vs. -1.10% (0.07) and
1.10% (0.07) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adjusted
mean (SE) changes from baseline in weight were -0.33kg (0.21) for placebo vs.
1.94kg (0.19) and -2.14kg (0.20) for empagliflozin 10 and 25mg, respectively
(both p<0.001). Adverse events were reported in 57.2% on placebo, 64.4% on
empagliflozin 10mg and 59.6% on empagliflozin 25mg. Genital infection AEs were
reported in 1.4% on placebo, 3.8% on empagliflozin 10mg, and 5.0% on
empagliflozin 25mg. CONCLUSIONS: In this specific population, empagliflozin in
combination with other oral agents, significantly reduced HbA1c and body weight
and was well tolerated.
PMID- 27499458
TI - Efficacy and safety of linagliptin in type 2 diabetes patients with self-reported
hepatic disorders: A retrospective pooled analysis of 17 randomized, double
blind, placebo-controlled clinical trials.
AB - AIMS: Liver disease is highly prevalent among people with type 2 diabetes
mellitus (T2DM). We evaluated the dipeptidyl peptidase-4 inhibitor linagliptin in
subjects with T2DM and hepatic disorders. METHODS: Data were pooled from 17
randomized, double-blind, placebo-controlled clinical trials of linagliptin in
T2DM subjects that included individuals with self-reported history of hepatic
disorders at baseline. The primary endpoint was change in HbA1c from baseline to
week 24. RESULTS: Of the 7009 participants (56% white, 39% Asian), 574 had
hepatic disorders, most commonly hepatic steatosis (60%). At week 24, adjusted
mean+/-standard error (SE) change in HbA1c from baseline in those with hepatic
disorders was -0.75%+/-0.05 with linagliptin and -0.20%+/-0.08 with placebo
[treatment difference: -0.54% (95% confidence interval-0.72 to -0.36); P<.0001].
There was no significant difference in HbA1c reduction between subjects with or
without baseline hepatic disorders (P=.4042). Among subjects with hepatic
disorders, 13.5% and 14.8% of the linagliptin and placebo groups, respectively,
reported drug-related adverse events while 10.4% and 15.9%, respectively,
reported hypoglycemia. Overall, adverse event rates were similar in individuals
with or without hepatic disorders. CONCLUSIONS: This large pooled analysis
suggests that linagliptin is effective and well tolerated in people with T2DM and
liver disease.
PMID- 27499460
TI - Antimicrobial effects of Piper hispidum extract, fractions and chalcones against
Candida albicans and Staphylococcus aureus.
AB - Three chalcones, 2'-hydroxy-4,4',6'-trimethoxychalcone, 2'-hydroxy-4,4',6'
tetramethoxychalcone, and 3,2'-dihydroxy-4,4',6'-trimethoxychalcone, were
isolated from the leaves of Piper hispidum in a bioguided fractionation of crude
extract. The antimicrobial activity of crude extract of P. hispidum leaves was
determined against bacteria Escherichia coli, Pseudomonas aeruginosa, Bacillus
subtilis, Staphylococcus aureus and yeasts Candida albicans, C. parapsilosis and
C. tropicalis. Fractions and chalcones were tested against C. albicans and S.
aureus. The checkerboard assay was performed to assess synergic interactions
between extract and antifungal drugs, and the 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyl tetrazolium bromide (MTT) reduction assay was used to evaluate anti
biofilm effects of extract. The extract was active against yeasts, S. aureus and
B. subtilis with MIC values between 15.6 and 62.5MUg/mL. Synergistic effects of
extract associated with fluconazole and nystatin were observed against C.
albicans, with fractional inhibitory concentration indices of 0.37 and 0.24,
respectively. The extract was also effective against C. albicans and S. aureus
biofilm cells at concentrations of 62.5 and 200MUg/mL, respectively. Thus, P.
hispidum may be a possible source of bioactive substances with antimicrobial
properties.
PMID- 27499459
TI - Parathyroid hormone/parathyroid hormone-related peptide regulate osteosarcoma
cell functions: Focus on the extracellular matrix (Review).
AB - Osteosarcoma (OS) is a primary bone tumor of mesenchymal origin mostly affecting
children and adolescents. The OS extracellular matrix (ECM) is extensively
altered as compared to physiological bone tissue. Indeed, the main characteristic
of the most common osteoblastic subtype of OS is non-mineralized osteoid
production. Parathyroid hormone (PTH) is a polypeptide hormone secreted by the
chief cells of the parathyroid glands. The PTH-related peptide (PTHrP) may be
comprised of 139, 141 or 173 amino acids and exhibits considerate N-terminal
amino acid sequence homology with PTH. The function of PTH/PTHrP is executed
through the activation of the PTH receptor 1 (PTHR1) and respective downstream
intracellular pathways which regulate skeletal development, bone turnover and
mineral ion homeostasis. Both PTHR1 and its PTH/PTHrP ligands have been shown to
be expressed in OS and to affect the functions of these tumor cells. This review
aims to highlight the less well known aspects of PTH/PTHrP functions in the
progression of OS by focusing on ECM-dependent signaling.
PMID- 27499461
TI - Evaluation of antifungal activity of standardized extract of Salvia rhytidea
Benth. (Lamiaceae) against various Candida isolates.
AB - OBJECTIVES: Salvia species have long been described in traditional medicine for
various indications. Owing to the widespread use of this genus by ethnic
populations, especially for various infections ranging from skin disease to
gastrointestinal disorders, we were encouraged to determine whether Salvia
rhytidea could be effective against fungal infections. Given the increased
incidence of candidiasis in the past decade, limits on the use of antifungal
drugs, emergence of azole-resistant Candida species and increased incidence of
treatment failures, it is necessary to identify a novel agent with antifungal
properties. Aim of the study was to evaluate the antifungal properties of S.
rhytidea against various Candida isolates. MATERIALS AND METHODS: In this study,
at first rosmarinic acid content of plant extract was determined. A total of 96
Candida isolates were tested, including the following species: Candida albicans
(n=42), Candida glabrata (n=16), Candida tropicalis (n=11), Candida krusei (n=9),
Candida parapsilosis (n=9), Candida lusitaniae (n=7) and Candida guilliermondii
(n=2). The in vitro antifungal activity of methanolic extracts of S. rhytidea
Benth. was evaluated against Candida isolates and compared with that of the
standard antifungal drug nystatin by using a broth microdilution method,
according to CLSI. RESULTS: Phytochemical screening results showed that the
methanolic extract of S. rhytidea Benth. was rich in flavonoids and tannins. The
minimal inhibitory concentration (MIC) and minimum fungicidal concentration (MFC)
values of S. rhytidea Benth. ranged from 3.125 to>100MUg/ml and 6.25 to>100MUg/ml
respectively. The growth inhibition value displayed that C. tropicalis, C. krusei
and C. albicans isolates were most susceptible to S. rhytidea. CONCLUSIONS:
Findings show that S. rhytidea possesses an antifungal effect against Candida
isolates.
PMID- 27499462
TI - Prisoners of Solitude: Bringing History to Bear on Prison Health Policy.
PMID- 27499463
TI - Improving the quality of written feedback using written feedback.
AB - BACKGROUND: Educational feedback is amongst the most powerful of all learning
interventions. RESEARCH QUESTIONS: (1) Can we measure the quality of written
educational feedback with acceptable metrics? (2) Based on such a measure, does a
quality improvement (QI) intervention improve the quality of feedback? STUDY
DESIGN: We developed a QI instrument to measure the quality of written feedback
and applied it to written feedback provided to medical students following
workplace assessments. We evaluated the measurement characteristics of the QI
score using generalisability theory. In an uncontrolled intervention, QI profiles
were fed back to GP tutors and pre and post intervention scores compared. STUDY
RESULTS: A single assessor scoring 6 feedback summaries can discriminate between
practices with a reliability of 0.82.The quality of feedback rose for two years
after the introduction of the QI instrument and stabilised in the third year. The
estimated annual cost to provide this feedback is L12 per practice.
Interpretation and recommendations: It is relatively straightforward and
inexpensive to measure the quality of written feedback with good reliability. The
QI process appears to improve the quality of written feedback. We recommend
routine use of a QI process to improve the quality of educational feedback.
PMID- 27499464
TI - Evaluation of paediatric radiology services in hospitals in the UK.
AB - AIM: To compare paediatric radiology provision across the UK with national
standards published by the Department of Health and the Royal College of
Radiologists (RCR). MATERIALS AND METHODS: Audit standards and indicators for
paediatric imaging were derived from "Delivering quality imaging services for
children",1 "Standards for imaging in cases of suspected non-accidental injury"2
and "Improving paediatric interventional radiology services"3 and agreed jointly
by the Clinical Radiology Audit Committee and the British Society of Paediatric
Radiology. A questionnaire was sent to all hospitals and NHS trusts imaging
children aged 16 or younger in the UK in October 2013. The target for all
indicators was 100%. Eighty-seven of 196 (44%) eligible institutions submitted
data, the size distribution of the institutions was representative when compared
to data from "Facing the future: a review of paediatric services"4 published by
the Royal College of Paediatrics and Child health. RESULTS: Only 65% of
paediatric images were obtained by staff who had had specific training and only
60% were reported by radiographers or radiologists with appropriate training.
Sixty-two percent of centres did not have access to a paediatric opinion 24 hours
a day, 7 days a week all year; only 34% of radiographers who regularly imaged
children had had any access to continuing professional development (CPD) in the
12 months of the audit. Although all hospitals had facilities for image transfer,
only 57% had any formal funding arrangements in place for external reporting of
images. CONCLUSIONS: The standards set for a network approach to paediatric
radiology provision in "Delivering quality imaging services for children" are
largely unmet. This failure to make the most of the workforce and resources puts
vulnerable children at risk. The authors urge NHS England to work with the RCR to
organise and administer a national network for paediatric imaging.
PMID- 27499465
TI - Commentary on: evaluation of paediatric radiology service in hospitals in the UK.
PMID- 27499466
TI - Stiffness at shear-wave elastography and patient presentation predicts upgrade at
surgery following an ultrasound-guided core biopsy diagnosis of ductal carcinoma
in situ.
AB - AIM: The aim of this study is to establish predictors of invasion in lesions
yielding an ultrasound-guided biopsy diagnosis of ductal carcinoma in situ
(DCIS). MATERIALS AND METHODS: Patients subjected to ultrasound-guided core
biopsy yielding DCIS were studied. At shear-wave elastography (SWE) a threshold
of 50 kPa was used for mean elasticity (Emean) to dichotomise the elasticity data
between invasive and non-invasive masses. Data recorded included the mammographic
and ultrasound features, the referral source, and grade of DCIS in the biopsy.
The chi-square test was used to detect statistical significance. RESULTS: Of 57
lesions, 24 (42%) had invasion at excision. Symptomatic patients and patients
with stiff lesions were more likely to have invasion than patients presenting
through screening and with soft lesions (58% [14 of 24] versus 30% [10 of 33],
p=0.03) and (51% [20 of 39] versus 22% [4 of 18], p=0.04). No other factors
showed a relationship with invasion. Combining the two predictors of invasion
improved risk stratification with symptomatic and stiff lesions having a risk of
invasion of 67% (12 of 18) and soft lesions presenting at screening having only a
17% (2 of 12) risk of invasion (p=0.02). CONCLUSION: Stiffness on SWE and the
referral source of the patient are predictors of occult invasion in women with an
ultrasound-guided core biopsy diagnosis of DCIS.
PMID- 27499467
TI - Analysis and Diagnosis of Upper Facial Region.
PMID- 27499468
TI - Botulinum Toxin Use in the Upper Face.
PMID- 27499469
TI - Injectable Fillers in the Upper Face.
PMID- 27499470
TI - Skin Resurfacing Procedures of the Upper Face.
PMID- 27499471
TI - Upper Eyelid Blepharoplasty.
PMID- 27499472
TI - Lower Transcutaneous Blepharoplasty.
PMID- 27499473
TI - Transconjunctival Lower Blepharoplasty.
AB - There is no secret to achieving successful results with lower belpharoplasties;
as is the case with any surgical procedure, proper patient evaluation and
development of a comprehensive, anatomic-based treatment plan are prerequisites
for success. For situations in which a patient has little lid laxity and
pseudoherniated periorbital fat, transconjunctival lower blepharoplasty is the
treatment of choice. Transconjunctival lower blepharoplasty enables the surgeon
to reposition fat, effectively blending the lid-cheek junction and filling the
tear trough deformity. In order to better enable clinicians to achieve optimal
outcomes, the authors advocate an anatomic-based approach for patient evaluation
and treatment planning.
PMID- 27499474
TI - Management of Lower Eyelid Laxity.
PMID- 27499475
TI - Open Brow Lift Surgery for Facial Rejuvenation.
PMID- 27499476
TI - The Endoscopic Brow Lift.
PMID- 27499477
TI - Management of Complications Associated with Upper Facial Rejuvenation.
PMID- 27499478
TI - Rejuvenation of the Facial Upper Third.
PMID- 27499480
TI - Editors' Introduction.
PMID- 27499479
TI - Upregulation of microRNA-370 promotes cell apoptosis and inhibits proliferation
by targeting PTEN in human gastric cancer.
AB - Growing evidence suggests that microRNA plays an essential role in the
development and metastasis of many tumors, including gastric cancer. Aberrant miR
370 expression has been indicated in tumor growth, but the mechanism of miR-370
inhibits both the proliferation and metastatic ability for gastric cancer remains
unclear. Accumulating evidence reported that PTEN signaling pathway plays an
important role in the cellular processes, such as apoptosis, cell growth and
proliferation. The goal of this study was to identify whether miR-370 could
inhibit the growth, migration, invasion, proliferation and metastasis of gastric
cancer through targeting PTEN. Real-time PCR (RT-PCR) was used to quantify miR
370 expression in vitro experiments. The biological functions of miR-370 were
determined via cell proliferation. Our study indicated that miR-370 targeted PTEN
leading to activation of apoptosis signaling and the cell proliferation of
cervical cancer cells, ameliorating gastric cancer growth and progression. In
addition, the combination of miR-370 and PTEN inactivated AKT, MDM2 and mTOR
while stimulated caspase-3, p53 and GSK3beta expression, promoting apoptosis and
suppressing proliferation of gastric cancer cells. Therefore, our study revealed
the mechanistic links between miR-370 and PTEN in the pathogenesis of gastric
cancer through modulation of cell apoptosis and proliferation. Additionally,
targeting miR-370 could serve as a novel strategy for future gastric cancer
therapy clinically.
PMID- 27499481
TI - Henry Beecher's Contributions to the Ethics of Clinical Research.
AB - In the 1950s and '60s, Henry Beecher pioneered the discussion of the ethics of
clinical research, leading eventually to the publication of the famous New
England Journal of Medicine article summarizing 22 research studies that Beecher
suggests were unethical. Those studies generally showed a pattern of posing
serious risks to subjects without anticipated proportional benefit. Beecher
famously claimed that the problem was not that researchers were malicious or
evil; rather, he claimed the problem was they manifested thoughtlessness or
carelessness. He called for more rigorous self-scrutiny rather than public
review.This article argues that Beecher's reliance on conscientious investigators
is problematic. In particular, it focuses on benefits and harms to the exclusion
of other moral criteria. However, both research subjects and public regulators
are also concerned about autonomy and the consent requirement, confidentiality,
and fairness in subject selection and research design. The movement in the 1970s
toward more public scrutiny was critical, even though Beecher was right in
holding that it was not "vicious disregard for subject welfare" that explained
unethical protocols.
PMID- 27499482
TI - "Ethics and Clinical Research" in Biographical Perspective.
AB - Henry K. Beecher (1904-1976) played an important role in the development of
bioethics. His 1966 article "Ethics and Clinical Research" in the New England
Journal of Medicine intensified concern about the welfare of patients
participating in clinical research, and his leadership in the 1968 Harvard Ad Hoc
Committee on Brain Death redefined the determination of death. Beecher deserves,
and even demands, explanation and explication. This essay offers a biographical
perspective on the Harvard professor. In addition to his early life and education
in both Kansas and Boston, the essay explores how Beecher's experiences in World
War II and in the new geopolitical realities of the Cold War shaped his views
about the ethical dilemmas of clinical research.
PMID- 27499483
TI - Beecher as Clinical Investigator: Pain and the Placebo Effect.
AB - Among the many contributions by Henry Beecher to science and clinical practice,
pain and the placebo effect certainly represent two of the most important
aspects. On the one hand, Beecher considered the pain experience not only as
arising from the peripheral injured tissues, but also as an emotional experience
that is capable of modulating the nociceptive input. On the other hand, he
analyzed the placebo effect at an unprecedented level for that time. His ideas
sparked from his work on wounded soldiers during World War II. In spite of the
unusual situation and the lack of sophisticated experimental tools on the
battlefield, Beecher succeeded in putting forward several important concepts, and
his ideas still pervade modern health care and research.
PMID- 27499484
TI - Moving Bioethics Toward Its Better Self: a sociologist's perspective.
AB - The value and belief questions with which bioethics deals have social, cultural,
moral, and societal implications that are not confined to certain spheres of
biology and medicine, health and illness, and the delivery of medical care. And
yet, throughout its history, the field has continued to be focused on a narrow
array of medically associated phenomena to which it has applied a limited set of
ethical precepts that originate in Western and American philosophical thought. It
has done so in an intellectual atmosphere that has not been characterized by
vigorous debate. This paper reflects on these attributes of bioethics, offers
some suggestions about how it might expand its topical, ethical, cross-cultural,
and international orbit, and invites participants in the field to bring this
about through a self-critical process.
PMID- 27499485
TI - Henry Knowles Beecher, Jay Katz, and the Transformation of Research with Human
Beings.
AB - The modern history of experimentation with human beings is notable for its
ethical lacunae, when even the clearest directives fail to prevent violations of
subjects' rights and welfare. One such lacuna occurred during the 25 years
between 1947, when the Nuremberg Code was articulated in the judgment passed on
the men who had performed medical experiments in the Nazi concentration camps,
and 1972, when the revelation of the 40-year-long Tuskegee Syphilis Study shocked
the public and pushed Congress to adopt legislation that eventually transformed
the governance of human subjects research. The work that Henry Beecher and Jay
Katz did on the ethics of human experimentation beginning in 1964-which was
mutually supportive but also divergent in its premises and prescriptions-played a
prominent role in the policy-making processes. Beecher, whose detailed disclosure
of the ethical lapses of leading researchers in his renowned 1966 New England
Journal of Medicine article initiated the policy reform process, proved less
influential in shaping those reforms than Katz. Ultimately, Beecher was one of
the last and best exemplars of "medical ethics," while Katz-in his service on the
Tuskegee Syphilis Study Ad Hoc Advisory Panel and in his testimony before, and
work with, the Senate Health subcommittee-was an early practitioner of bioethics,
a field in which the rules are not all written and applied by the medical
profession but arise through a messier process involving outsiders and formal
regulatory decisions.
PMID- 27499486
TI - Henry Beecher and Consent to Research: a critical re-examination.
AB - Henry Beecher is an iconic figure in research ethics, best known for blowing the
whistle on unethical clinical research in 1966. This article traces the evolution
of Beecher's view on consent to research and juxtaposes these views with his own
practices relating to informed consent in the conduct of clinical research.
Additionally, critical examination of Beecher's conception of informed consent as
an ideal has important implications for contemporary research ethics.
PMID- 27499487
TI - Henry K. Beecher and the Oversight of Research in Children.
AB - Henry K. Beecher was a pioneer of research ethics and a prominent whistleblower
with regard to ethically problematic studies. Most of his work focused on
research in adults, not children, but he did speculate about the implications of
his ethical concerns for research in minors. This paper reviews Beecher's
response to Krugman's studies of hepatitis at the Willowbrook State School and
the debate that Beecher's article stimulated between Ramsey and McCormick. That
debate shaped the terms that were used in current federal regulations for
research in children. The paper then speculates about whether Beecher would have
approved of our current regulatory system.
PMID- 27499488
TI - Acid Brothers: Henry Beecher, Timothy Leary, and the psychedelic of the century.
AB - Henry Knowles Beecher, an icon of human research ethics, and Timothy Francis
Leary, a guru of the counterculture, are bound together in history by the
synthetic hallucinogen lysergic acid diethylamide (LSD). Both were associated
with Harvard University during a critical period in their careers and of drastic
social change. To all appearances the first was a paragon of the establishment
and a constructive if complex hero, the second a rebel and a criminal, a rogue
and a scoundrel. Although there is no evidence they ever met, Beecher's indirect
struggle with Leary over control of the 20th century's most celebrated
psychedelic was at the very heart of his views about the legitimate, responsible
investigator. That struggle also proves to be a revealing bellwether of the
increasingly formalized scrutiny of human experiments that was then taking shape.
PMID- 27499489
TI - The Role of the Virtuous Investigator in Protecting Human Research Subjects.
AB - In his famous 1966 New England Journal of Medicine article, Henry Beecher
concluded that a critical safeguard for protecting human participants, more
reliable than informed consent, was the "presence of an intelligent, informed,
conscientious, compassionate, responsible investigator." This article examines
Beecher's appeal to reliance on the "virtuous" investigator in light of the
critical role that investigators play in research ethics and the systems of
research protections that have been developed since Beecher's writing. It
addresses the extent to which research ethics rely on virtuous investigators; the
meaning of virtuous, as distinct from compliance with the rules and regulations
that guide ethical research; the particular virtues that it might be important
for investigators to have; and the impact of the existing system of human
subjects protections on the virtuous investigator. The virtuous investigator who
is motivated to take ethical responsibilities seriously is an essential safeguard
for the protection of human research participants and an important complement to
the system of oversight protections. However, since the current human subjects
protection system does not promote virtue or ethical resourcefulness by
investigators, attention to enhancing a culture of professional responsibility
might serve to forge a synergy between the protections afforded by the current
oversight system and those provided by the virtuous investigator.
PMID- 27499490
TI - Clinical Trials Without Consent?
AB - Fifty years after Beecher's landmark article, an old question is being debated
anew: is it ethical to conduct clinical research without consent? This paper
provides a systematic analysis of this question. First, it describes five
clinical trials that have either been conducted (or proposed) without the
subjects providing consent. Second, it reviews a number of conditions that are
often provided to justify bypassing of consent and finds that only some of them
qualify as necessary conditions for bypassing consent. When those conditions are
applied to the clinical trials, only one trial without consent (a type of cluster
randomized trial) appears clearly justified; bypassing consent in the remaining
four trials is more questionable. The present analysis may be useful in the
interpretation of the current U.S. regulations that provide for waivers and
alterations of informed consent.
PMID- 27499491
TI - Electronic Processes within Quantum Dot-Molecule Complexes.
AB - The subject of this review is the colloidal quantum dot (QD) and specifically the
interaction of the QD with proximate molecules. It covers various functions of
these molecules, including (i) ligands for the QDs, coupled electronically or
vibrationally to localized surface states or to the delocalized states of the QD
core, (ii) energy or electron donors or acceptors for the QDs, and (iii)
structural components of QD assemblies that dictate QD-QD or QD-molecule
interactions. Research on interactions of ligands with colloidal QDs has revealed
that ligands determine not only the excited state dynamics of the QD but also, in
some cases, its ground state electronic structure. Specifically, the article
discusses (i) measurement of the electronic structure of colloidal QDs and the
influence of their surface chemistry, in particular, dipolar ligands and exciton
delocalizing ligands, on their electronic energies; (ii) the role of molecules in
interfacial electron and energy transfer processes involving QDs, including
electron-to-vibrational energy transfer and the use of the ligand shell of a QD
as a semipermeable membrane that gates its redox activity; and (iii) a particular
application of colloidal QDs, photoredox catalysis, which exploits the
combination of the electronic structure of the QD core and the chemistry at its
surface to use the energy of the QD excited state to drive chemical reactions.
PMID- 27499492
TI - Dose estimation derived from the exposure to radon, thoron and their progeny in
the indoor environment.
AB - The annual exposure to indoor radon, thoron and their progeny imparts a major
contribution to inhalation doses received by the public. In this study, we report
results of time integrated passive measurements of indoor radon, thoron and their
progeny concentrations that were carried out in Garhwal Himalaya with the aim of
investigating significant health risk to the dwellers in the region. The
measurements were performed using recently developed LR-115 detector based
techniques. The experimentally determined values of radon, thoron and their
progeny concentrations were used to estimate total annual inhalation dose and
annual effective doses. The equilibrium factors for radon and thoron were also
determined from the observed data. The estimated value of total annual inhalation
dose was found to be 1.8 +/- 0.7 mSv/y. The estimated values of the annual
effective dose were found to be 1.2 +/- 0.5 mSv/y and 0.5 +/- 0.3 mSv/y,
respectively. The estimated values of radiation doses suggest no important health
risk due to exposure of radon, thoron and progeny in the study area. The
contribution of indoor thoron and its progeny to total inhalation dose ranges
between 13-52% with mean value of 30%. Thus thoron cannot be neglected when
assessing radiation doses.
PMID- 27499493
TI - Left ventricular area on non-contrast cardiac computed tomography as a predictor
of incident heart failure - The Multi-Ethnic Study of Atherosclerosis.
AB - BACKGROUND: The use of non-contrast cardiac computed tomography measurements to
predict heart failure (HF) has not been studied. In the present study we
evaluated the prognostic value of left ventricular area adjusted for the body
surface area (LVA-BSA) measured by non-contrast cardiac CT to predict incident HF
and cardiovascular disease (CVD) events. METHODS: We studied left ventricular
dimensions and calculated LVA-BSA in 6781 participants of the MESA study (mean
age: was 62 +/- 10 years, 53% females; 62% non-white) free from prior HF who
underwent non-contrast cardiac CT to evaluate the coronary artery calcium score
(CAC) at baseline and were followed up for a median of 10.2 years. RESULTS:
During follow up, 237 (3.5%) incident HF and 475 (7.0%) CVD events occurred.
After adjustment for clinical variables and CAC, LVA-BSA was significantly
associated with incident HF (hazard ratio [HR]: 1.10 per 100 mm2/m2, p < 0.001)
and CVD events (HR: 1.07 per 100 mm2/m2, p < 0.001). The area under the ROC curve
for the prediction of incident HF improved from 0.787 on a model including only
risk factors to 0.798 when CAC was added (p = 0.02), and to 0.816 with the
additional inclusion of LVA-BSA (p = 0.007). Similar improvements for the
prediction of CVD events were noted. CONCLUSION: In an ethnically diverse
population of asymptomatic individuals free from baseline CVD or HF, the left
ventricular area measured by non-contrast cardiac CT is a strong predictor of
incident HF events beyond traditional risk factors and CAC score.
PMID- 27499494
TI - The Ratio of Regulatory (FOXP3+) to Total (CD3+) T Cells Determined by Epigenetic
Cell Counting and Cardiovascular Disease Risk: A Prospective Case-cohort Study in
Non-diabetics.
AB - BACKGROUND: Experimental and clinical evidence indicate that inflammatory
processes in atherogenesis and the development of cardiovascular complications
are promoted by a loss of regulatory T cell (Treg)-mediated immunological
tolerance to plaque antigens. Yet, the association between alterations of
systemic Treg frequency and cardiovascular disease incidence remains uncertain.
METHODS: A nested case-cohort study was conducted within the European Prospective
Investigation into Cancer and Nutrition (EPIC)-Heidelberg, comprising a random
subcohort (n=778) and primary cases of myocardial infarction (MI, n=276) and
ischemic stroke (n=151). Pre-diagnostic FOXP3+ Treg and total CD3+ T-lymphocyte
(tTL) frequencies in blood were measured by epigenetic-based, quantitative real
time PCR-assisted cell counting. RESULTS: Multivariate, Prentice-weighted Cox
regression analyses revealed that lower Treg/tTL ratios were not associated with
the risk of either MI (lowest vs. highest sex-specific quartile; hazard ratio:
0.72, 95% confidence interval: 0.46 to 1.13; Ptrend=0.51) or stroke (HR: 0.90,
95% CI: 0.51 to 1.60; Ptrend=0.78). There were no correlations of Treg/tTL ratios
with C-reactive protein, HbA1c, and various lipid parameters. CONCLUSIONS: Among
middle-aged adults from the general population, imbalances in the relative
frequency of Tregs within the total T cell compartment do not confer an increased
risk of MI or stroke.
PMID- 27499495
TI - Hostile takeover: Manipulation of HIF-1 signaling in pathogen-associated cancers
(Review).
AB - Hypoxia-inducible factor (HIF)-1 is a central regulator in the adaptation process
of cell response to hypoxia (low oxygen). Emerging evidence has demonstrated that
HIF-1 plays an important role in the development and progression of many types of
human diseases, including pathogen-associated cancers. In the present review, we
summarize the recent understandings of how human pathogenic agents including
viruses, bacteria and parasites deregulate cellular HIF-1 signaling pathway in
their associated cancer cells, and highlight the common molecular mechanisms of
HIF-1 signaling activated by these pathogenic infection, which could act as
potential diagnostic markers and new therapeutic strategies against human
infectious cancers.
PMID- 27499496
TI - The difference in activity of daily living (ADL) and mortality in patients aged
over 80 years with femoral neck fracture treated with hemiarthroplasty or
osteosynthesis at 2 years of follow-up.
AB - INTRODUCTION: Hip fractures are one of the major causes of morbidity and
mortality in the elderly and outcomes following hip fracture have been the focus
of several studies over recent decades. Among all types of fall-related injuries,
hip fractures cause the greatest number of deaths, lead to severe health problems
and reduce quality of life. Improving the outcome of hip fracture surgery has
thus become one of the main areas of interest for orthopaedic surgeons. The aim
of this study was to compare the difference in activity of daily living (ADL) and
mortality between patients aged over 80 years with hip fracture treated with
osteosynthesis versus prosthesis at 2 years of follow-up. MATERIALS AND METHODS:
The data were collected on admission and during in-hospital stay. Information
recorded on admission included: age, sex, type and mechanism of fracture,
functional and cognitive status, comorbidity, and severity of illness.
Prefracture functional status was measured. The follow-up was clinical and
radiographical, or was by telephone for patients who were not able to come to the
clinic. Patients aged over 80 years who underwent a single surgical procedure
treated with intramedullary nail or hemiarthroplasty were included in the study.
RESULTS: A total of 174 patients (45 male and 129 female) were included in the
study. The two treatment groups were comparable for all preoperative parameters
except for preoperative haemoglobin, which was an average of 1g/dl higher in the
patients given hemiarthroplasty compared with those treated with intramedullary
nail (t-test: p<0.05). The average observation period was 594.99days; the number
of deaths was 62 of 164 contacted patients, and the survival rate at 2 years was
62.2%. There was increased mortality in patients who underwent hemiarthroplasty
(Log-rank Mantel-Cox, p: 0,048). The difference in ADL between preoperative and
follow-up is not statistically significant between the two groups. DISCUSSION: In
the literature, there are few specific studies that consider these parameters in
this population. However, these findings are consistent with the findings from
other studies. CONCLUSION: Patients who received hemiarthroplasty have a higher
mortality risk than those treated with intramedullary nail; there are no
differences in ADL at follow-up.
PMID- 27499497
TI - Investigating distribution pattern of species in a warm-temperate conifer
broadleaved-mixed forest in China for sustainably utilizing forest and soils.
AB - The maintaining mechanisms and potential ecological processes of species
diversity in warm temperate- conifer-broadleaved-mixed forest are far from clear
understanding. In this paper, the relative neighborhood density Omega was used to
analyze the spatial distribution patterns of 34 species with >=11 individuals in
a warm- temperate-conifer-broadleaved-mixed forest, northern China. Then we used
canonical correspondence analysis (CCA) and Torus-translation test (TTT) to
explain the distribution of observed species. Our results show that aggregated
distribution is the dominant pattern in warm-temperate natural forest and four
species regular distribution at the spatial scale >30m. The aggregated percentage
and intensity decline with spatial scale, abundance and size classes increasing.
Rare species are aggregated more than intermediate and abundant species. These
results prove sufficiently the effects existence of scale separation, self
thinning and Janzen-Connell hypothesis. In addition, functional traits (dispersal
modes and shade tolerance) also have a significant influence on distribution of
species. The results of CCA confirm that slope and convexity are the most
important factors affecting the distribution of tree species distribution,
elevation and slope of shrub species though the combination of topographic
variables only explained 1% of distribution of tree species and 2% of shrub
species. Most species don't have habitat preference; however 47.1% (16/34)
species including absolutely dominant tree (Pinus tabulaeformis and Quercus
wutaishanica) and shrub species (Rosa xanthina) and most other species with
important value in the front, are strongly positively or negatively associated
with at least one habitat. The valley and ridge are most distinct habitat with
association of 12 species in the plot. However, high elevation slope with 257
quadrats is the most extensive habitat with only four species. Therefore, there
is obvious evidence that habitat heterogeneity play an important role on shaping
spatial distribution of species in warm temperate forest. Our research results
provide significant evidence that dispersal limitation and habitat heterogeneity
have a contribution jointly to regulating the spatial distribution pattern of
species in warm-temperate-forest in China.
PMID- 27499498
TI - Evaluating the evolution of the Heihe River basin using the ecological network
analysis: Efficiency, resilience, and implications for water resource management
policy.
AB - One of the most critical challenges in the anthropocentric age is the sustainable
management of the planet's increasingly strained water resources. In this avenue,
there is a need to advance holistic approaches and objective tools which allow
policy makers to better evaluate system-level properties and trade-offs of water
resources. This research contributes to the expanding literature in this area by
examining the changes to system-level network configurations of the middle
reaches of the Heihe River basin from 2000 to 2009. Specifically, through the
ecological network analysis (ENA) approach, this research examines changes to the
system-level properties of efficiency, redundancy, and evaluates the trade-offs
to the resiliency of ecosystem water services of the middle reaches of the Heihe
River basin. Our results indicate that while the efficiency of the middle reaches
has increased from 2000 to 2009 by 6% and 78% more water is released to the lower
reaches, the redundancy of the system has also decreased by 6%. The lower level
of redundancy, particularly due to the changes in the groundwater body levels,
has critical long-term consequences for the resilience of the water ecosystem
services of the middle reaches. In consideration of these holistic trade-offs,
two hypothetical alternative scenarios, based on water recycling and saving
strategies, are developed to improve the long-term health and resilience of the
water system.
PMID- 27499499
TI - Analysing the impact of multiple stressors in aquatic biomonitoring data: A
'cookbook' with applications in R.
AB - Multiple stressors threaten biodiversity and ecosystem integrity, imposing new
challenges to ecosystem management and restoration. Ecosystem managers are
required to address and mitigate the impact of multiple stressors, yet the
knowledge required to disentangle multiple-stressor effects is still incomplete.
Experimental studies have advanced the understanding of single and combined
stressor effects, but there is a lack of a robust analytical framework, to
address the impact of multiple stressors based on monitoring data. Since 2000,
the monitoring of Europe's waters has resulted in a vast amount of biological and
environmental (stressor) data of about 120,000 water bodies. For many reasons,
this data is rarely exploited in the multiple-stressor context, probably because
of its rather heterogeneous nature: stressors vary and are mixed with broad-scale
proxies of environmental stress (e.g. land cover), missing values and zero
inflated data limit the application of statistical methods and biological
indicators are often aggregated (e.g. taxon richness) and do not respond stressor
specific. Here, we present a 'cookbook' to analyse the biological response to
multiple stressors using data from biomonitoring schemes. Our 'cookbook' includes
guidance for the analytical process and the interpretation of results. The
'cookbook' is accompanied by scripts, which allow the user to run a stepwise
analysis based on his/her own data in R, an open-source language and environment
for statistical computing and graphics. Using simulated and real data, we show
that the recommended procedure is capable of identifying stressor hierarchy
(importance) and interaction in large datasets. We recommend a minimum number of
150 independent observations and a minimum stressor gradient length of 75% (of
the most relevant stressor's gradient in nature), to be able to reliably rank the
stressor's importance, detect relevant interactions and estimate their
standardised effect size. We conclude with a brief discussion of the advantages
and limitations of this protocol.
PMID- 27499500
TI - A proposal for the organization of the referral of patients with chronicnon
specific low back pain.
AB - BACKGROUND: Low back pain in general and specifically chronic low back pain forms
a major burden for the patient and society. Recently studies demonstrated that up
to 65% of patients evolve to chronic pain as opposed to the previously accepted
8%. As low back pain patients present first with their general practitioner, the
latter should establish a treatment plan, including the appropriate referrals.
There are, however, no clear guidelines as to how to refer low back pain
patients. The process of trial and error of different specialties and treatment
possibilities often results in a long and costly trajectory. A better
understanding of the subtypes of chronic low back pain, the risks for
chronification and fast adequate referral may result in higher patient
satisfaction and cost reduction. Proposed solutions: We propose a classification
system based on the clinical and anatomical characteristics of axial low back
pain, separated from radicular pain. It is important to recognize the risks for
chronification, such as degenerative and/or herniated disk, a smaller cross
sectional area of the multifidus, erector spinae, and psoas muscles and
psychological and social factors, to be able to provide appropriate management.
Also stratification of the patients according to the degree of disability may
help in defining the correct treatment approach. A one-and-a-half line approach,
where a spine physician assistant works under the supervision of the general
practitioner to establish the sub-diagnosis, the risk factors for chronicity and
to explain the proposed management plan to the patient, may be helpful for an
early appropriate treatment selection for the patient with chronic low back pain.
PMID- 27499501
TI - Sugar beet factory lime affects the mobilization of Cd, Co, Cr, Cu, Mo, Ni, Pb,
and Zn under dynamic redox conditions in a contaminated floodplain soil.
AB - The impact of sugar beet factory lime (SBFL) on the release dynamics and
mobilization of toxic metals (TMs) under dynamic redox conditions in floodplain
soils has not been studied up to date. Therefore, the aim of this study was to
verify the scientific hypothesis that SBFL is able to immobilize Cd, Co, Cr, Cu,
Fe, Mn, Mo, Ni, Pb, and Zn under different redox potentials (EH) in a
contaminated floodplain soil. For this purpose, the non-treated contaminated soil
(CS) and the same soil treated with SBFL (CS+SBFL) were flooded in the laboratory
using a highly sophisticated automated biogeochemical microcosm apparatus. The
experiment was conducted stepwise from reducing (-13 mV) to oxidizing (+519 mV)
soil conditions. Soil pH decreased under oxic conditions in CS (from 6.9 to 4.0)
and in CS+SBFL (from 7.5 to 4.4). The mobilization of Cu, Cr, Pb, and Fe were
lower in CS+SBFL than in CS under both reducing/neutral and oxic/acidic
conditions. Those results demonstrate that SBFL is able to decrease
concentrations of these elements under a wide range of redox and pH conditions.
The mobilization of Cd, Co, Mn, Mo, Ni, and Zn were higher in CS+SBFL than in CS
under reducing/neutral conditions; however, these concentrations showed an
opposite behavior under oxic/acidic conditions and were lower in CS+SBFL than in
CS. We conclude that SBFL immobilized Cu, Cr, Pb, and Fe under dynamic redox
conditions and immobilized Cd, Co, Mn, Mo, Ni, and Zn under oxic acidic
conditions; however, the latter elements were mobilized under reducing neutral
conditions in the studied soil. Therefore, the addition of SBFL to acid
floodplain soils contaminated with TMs might be an important alternative for
ameliorating these soils with view to a sustainable management of these soils.
PMID- 27499502
TI - Use of sediment source fingerprinting to assess the role of subsurface erosion in
the supply of fine sediment in a degraded catchment in the Eastern Cape, South
Africa.
AB - Sediment source fingerprinting has been successfully deployed to provide
information on the surface and subsurface sources of sediment in many catchments
around the world. However, there is still scope to re-examine some of the major
assumptions of the technique with reference to the number of fingerprint
properties used in the model, the number of model iterations and the potential
uncertainties of using more than one sediment core collected from the same
floodplain sink. We investigated the role of subsurface erosion in the supply of
fine sediment to two sediment cores collected from a floodplain in a small
degraded catchment in the Eastern Cape, South Africa. The results showed that
increasing the number of individual fingerprint properties in the composite
signature did not improve the model goodness-of-fit. This is still a much debated
issue in sediment source fingerprinting. To test the goodness-of-fit further, the
number of model repeat iterations was increased from 5000 to 30,000. However,
this did not reduce uncertainty ranges in modelled source proportions nor improve
the model goodness-of-fit. The estimated sediment source contributions were not
consistent with the available published data on erosion processes in the study
catchment. The temporal pattern of sediment source contributions predicted for
the two sediment cores was very different despite the cores being collected in
close proximity from the same floodplain. This highlights some of the potential
limitations associated with using floodplain cores to reconstruct catchment
erosion processes and associated sediment source contributions. For the source
tracing approach in general, the findings here suggest the need for further
investigations into uncertainties related to the number of fingerprint properties
included in un-mixing models. The findings support the current widespread use of
<=5000 model repeat iterations for estimating the key sources of sediment
samples.
PMID- 27499503
TI - Melatonin mediated antidepressant-like effect in the hippocampus of chronic
stress-induced depression rats: Regulating vesicular monoamine transporter 2 and
monoamine oxidase A levels.
AB - The hippocampus is sensitive to stress which activates norepinephrine terminals
deriving from the locus coeruleus. Melatonin exerts positive effects on the
hippocampal neurogenic process and on depressive-like behaviour. Thus, in the
present study, an examination was made of the effect of chronic melatonin
treatment on norepinephrine content, synthesis, uptake, vesicular transport and
degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying
the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT.
The results show that CUMS evoked prolonged immobility. Melatonin treatment
decreased immobility in comparison with the placebo group, reflecting an
antidepressant-like effect. Compared with the placebo group, a dramatic decrease
in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A
protein levels in the hippocampus of the CUMS rats were observed. However, no
significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO
A mRNA levels between the placebo and the stressed groups were found. The results
showed the restorative effects of melatonin on the stress-induced decline in the
norepinephrine content of the hippocampus. It was observed that melatonin
treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA
and protein levels, whereas it reduced the increase of the mRNA of COMT and
protein levels of MAO-A. Chronic treatment with melatonin failed to alter the
gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally,
the results show that melatonin enhances VMAT2 expression and norepinephrine
storage, whilst it reduces norepinephrine degrading enzymes.
PMID- 27499504
TI - Simple mesothelial pericardial cyst in a rare location.
AB - Pericardial cysts are rare and generally benign intrathoracic lesions, most
frequently located in the cardiophrenic angles, but other locations have been
described. We present a case of a pericardial cyst in a previously undescribed
site. Our patient presented with a cyst in the interventricular septum which was
discovered as an incidental finding. After surgical excision of the cyst, it was
described pathologically as a simple mesothelial pericardial cyst. The
explanation of this rare condition is uncertain, but some hypotheses can be
outlined.
PMID- 27499505
TI - Active fixation coronary sinus lead extraction - A safe procedure.
PMID- 27499506
TI - Editorial.
PMID- 27499507
TI - Editorial.
PMID- 27499508
TI - Changes in lung sounds during asthma progression in a guinea pig model.
AB - BACKGROUND: Lung sound analysis is useful for objectively evaluating airways even
in children with asymptomatic asthma. However, the relationship between lung
sounds and morphological changes in the airways has not been elucidated. We
examined the relationship between lung sounds and chronic morphological changes
in the airways during the progression of asthma from onset in guinea pigs.
METHODS: Eleven male guinea pigs were examined; of these, seven were used as
asthma models and four as controls. The asthma models were sensitized and
repeatedly challenged by inhaling albumin chicken egg. We measured lung sounds
and lung function twice a week for 21 weeks. After the final antigen challenge,
the lungs were excised for histological examination. We measured the ratio of
airway wall thickness to the total airway area and the ratio of the internal area
to the total airway area in the trachea, third bronchi, and terminal bronchioles.
RESULTS: Among the lungs sounds, the difference between the two groups was
greatest with respect to inspiratory sound intensity. The ratio of airway wall
thickness to the total airway area of the terminal bronchioles was greater in the
asthma models than in the controls, and it correlated best with the changes in
inspiratory sound intensity in the 501-1000-Hz range (r = 0.76, p < 0.003).
CONCLUSIONS: Lung sound intensity in the middle frequency range from 501 to 1000
Hz correlated with peripheral airway wall thickness. Inspiratory sound intensity
appeared to be an indicator of morphological changes in small airways in asthma.
PMID- 27499509
TI - Nutrition in the spotlight: metabolic effects of environmental light.
AB - Use of artificial light resulted in relative independence from the natural light
dark (LD) cycle, allowing human subjects to shift the timing of food intake and
work to convenient times. However, the increase in artificial light exposure
parallels the increase in obesity prevalence. Light is the dominant Zeitgeber for
the central circadian clock, which resides within the hypothalamic
suprachiasmatic nucleus, and coordinates daily rhythm in feeding behaviour and
metabolism. Eating during inappropriate light conditions may result in metabolic
disease via changes in the biological clock. In this review, we describe the
physiological role of light in the circadian timing system and explore the
interaction between the circadian timing system and metabolism. Furthermore, we
discuss the acute and chronic effects of artificial light exposure on food intake
and energy metabolism in animals and human subjects. We propose that living in
synchrony with the natural daily LD cycle promotes metabolic health and increased
exposure to artificial light at inappropriate times of day has adverse effects on
metabolism, feeding behaviour and body weight regulation. Reducing the negative
side effects of the extensive use of artificial light in human subjects might be
useful in the prevention of metabolic disease.
PMID- 27499510
TI - Ambident Reactivity of Acetyl- and Formyl-Stabilized Phosphonium Ylides.
AB - The kinetics and mechanism of the reactions of formyl-stabilized ylide Ph3P?CHCHO
(1) and acetyl-stabilized ylide Ph3P?CHCOMe (2) with benzhydrylium ions
(Ar2CH(+), 3) were investigated by UV-vis and NMR spectroscopy. As ambident
nucleophiles, ylides 1 and 2 can react at oxygen as well as at the alpha-carbon.
For some reactions, it was possible to determine the second-order rate constant
for O-attack as well as for C-attack and to derive the nucleophile-specific
parameters N and sN according to the correlation lg k (20 degrees C) = sN(E + N)
for both nucleophilic sites. Generally, O-attack of benzhydrylium ions is faster
than C-attack. However, the initially formed benzhydryloxyvinylphosphonium ions
can only be observed by NMR spectroscopy when benzhydryl cations with high Lewis
acidity are employed. In other cases, rearrangement to the thermodynamically more
stable products arising from C-attack occurs. The results derived from our
investigations are employed to rationalize the behavior of ambident nucleophiles
1 and 2 in reactions with carbon-centered electrophiles in general. It is shown
that the principle of hard and soft acids and bases (HSAB) and the related
Klopman-Salem concept of charge and orbital control lead to incorrect predictions
of regioselectivity. We also show that the rate of the Wittig reaction of ylide 2
with aldehyde 14 is significantly faster than the rate of either C- or O-attack
calculated using lg k (20 degrees C) = sN(E + N), thus indicating that the
oxaphosphetane is formed by a concerted [2 + 2] cycloaddition.
PMID- 27499511
TI - Increase of prevalence of craniosynostosis.
AB - INTRODUCTION: Craniosynostosis represents premature closure of cranial sutures.
Prevalence is approximately 3.1-6.4 in 10.000 live births, which is reportedly
rising. This epidemiologic study aims to provide insight into this rise through
an accurate description of the prevalence, exploring regional variation and
change over time. METHODS: The Dutch Association for Cleft Palate and
Craniofacial Anomalies was consulted to identify patients with craniosynostosis
born between 2008 and 2013. Data were verified using data provided by all
hospitals that treated these patients. The following data were collected: date of
birth, gender, diagnosis and postal code. Previously reported data from 1997
until 2007 were included to assess for change in prevalence over the years.
RESULTS: Between 2008 and 2013 759 patients with craniosynostosis were born in
the Netherlands. Prevalence of craniosynostosis was 7.2 per 10.000 live births.
Sagittal synostosis was the most common form (44%). Poisson regression analysis
showed a significant mean annual increase of prevalence of total craniosynostosis
(+12.5%), sagittal (+11.7%) and metopic (+20.5%) synostosis from 1997 to 2013.
CONCLUSION: The prevalence of craniosynostosis is 7.2 per 10.000 live born
children in the Netherlands. Prevalence of total craniosynostosis, sagittal and
metopic suture synostosis has risen significantly from 1997 until 2013, without
obvious cause.
PMID- 27499512
TI - Clinical assessment scoring system for tracheostomy (CASST) criterion: Objective
criteria to predict pre-operatively the need for a tracheostomy in head and neck
malignancies.
AB - BACKGROUND: Tracheostomy is a mainstay modality for airway management for
patients with head-neck cancer undergoing surgery. This study aims to define
factors predicting need of tracheostomy and define an effective objective
criterion to predict tracheostomy need. METHODS: 486 patients undergoing
composite resections were studied. Factors analyzed were age, previous surgery,
extent of surgery, trismus, extent of mandibular resection and reconstruction
etc. Factors were divided into major and minor, using the clinical assessment
scoring system for tracheostomy (CASST) criterion. RESULTS: Sixty seven (13.7%)
patients required tracheostomy for their peri-operative management. Elective
tracheostomies were done in 53 cases during surgery and post-operatively in 14
patients. All patients in whom tracheostomies were anticipated had a score of
seven or more. CONCLUSION: A decision on whether or not an elective tracheotomy
in head and neck surgery is necessary and can be facilitated using CASST
criterion, which has a sensitivity of 95.5% and a negative predictive value (NPV)
of 99.3%. It may reduce post-operative complications and contribute to safer
treatment.
PMID- 27499513
TI - Simultaneous maxillo-mandibular distraction in early adolescence as a single
treatment modality for durable correction of type II unilateral hemifacial
microsomia: Follow-up till completion of growth.
AB - BACKGROUND: Timing of surgical intervention in hemifacial microsomia (HFM) is
controversial. Although mandibular osteodistraction in childhood for HFM is
popular, recent data for single-stage distraction in growing HFM patients
demonstrated long-term relapse. Literature suggests that adolescents in the late
mixed dentition age or permanent dentition age (11-16-year-old) had more stable
outcomes post-distraction than younger children. We present favorable experience
using single-treatment simultaneous maxillo-mandibular distraction in early
adolescent Pruzansky-Kaban type II HFM patients. METHODS: This was a
retrospective longitudinal study of seven consecutive type IIa/b HFM growing
patients (12-16-year-old) treated with simultaneous maxillo-mandibular
distraction. Oral commissure cant was photographically measured preoperatively
and at 6 months and annually ranging 3-7 years post-distraction. Ramus height and
chin deviation were measured from radiographs done preoperatively and at
distractor-removal, 1 year, 2 years, and 4 years post-distraction. RESULTS:
Average age at osteodistraction and at latest follow-up was 13.7 and 18.6 years,
respectively. Improvement was significant (p < 0.05) and sustained for mean oral
commissure cant (5.1 degrees -0.41 degrees ), mean ramus height ratio (0.59
0.86), and average chin deviation (15.9 mm-1.2 mm). Two subjects had mandibular
branch palsy and one had mild pin-tract infection - all resolved. All were
satisfied with their facial appearance. CONCLUSION: We have demonstrated good
lasting outcomes at completion of growth with single-stage simultaneous maxillo
mandibular distraction for type II HFM adolescents in the late mixed-dentition or
older age, and advocate this as an alternative to osteodistraction or
orthognathic surgery upon skeletal maturity.
PMID- 27499514
TI - Radiochemotherapy for locally advanced squamous cell carcinoma of the head and
neck: Higher-dose cisplatin every 3 weeks versus cisplatin/5-fluorouracil every 4
weeks.
AB - Many patients with locally advanced squamous cell carcinoma of the head and neck
(LASCCHN) receive cisplatin-based radiochemotherapy. The optimal regimen is still
unclear when considering both efficacy and feasibility. This study compared two
regimens for locoregional control (LRC), overall survival (OS), and adverse
events. Data of 329 patients with LASCCHN receiving definitive or postoperative
radiochemotherapy were retrospectively analyzed. A total of 131 patients received
100 mg/m(2) cisplatin on days 1, 22, and 43 (group A), and 198 patients received
20 mg/m(2) cisplatin plus 600/1000 mg/m(2) 5-FU on days 1-5 and days 29-33 (group
B). Radiochemotherapy regimens plus nine factors were compared for LRC and OS,
and radiochemotherapy regimens additionally for adverse events. On univariate
analysis, chemotherapy type was not associated with LRC (p = 0.36). On
multivariate analysis, performance score (p = 0.039), N-category (p = 0.007),
histologic grade (p = 0.007), upfront surgery (p = 0.030), and pre
radiochemotherapy hemoglobin levels (p < 0.001) were associated with LRC. On
univariate analysis, chemotherapy type had no impact on OS (p = 0.64). On
multivariate analysis, performance score (p < 0.001), T-category (p = 0.025), N
category (p < 0.001), histologic grade, and hemoglobin levels (p < 0.001) were
associated with OS. Renal failure occurred significantly more often in group A (p
= 0.008). Otherwise, adverse events were not significantly different. Thus, both
radiochemotherapy regimens appeared similarly effective for LASCCHN. Patients
receiving 100 mg/m(2) of cisplatin require close monitoring of their renal
function.
PMID- 27499515
TI - Peroneal artery-vein index as a potential factor of thrombosis occurrence in free
osteocutaneous fibula flap.
AB - BACKGROUND: Despite high popularity and great success rates of free
osteocutaneous fibula flaps, the flap failure caused by vascular thrombosis is
still a challenging problem. The authors present their evaluation of a potential
thrombosis risk factor - a peroneal artery-vein index. METHODS: The authors
evaluated the diameters of peroneal vessels and peroneal artery-vein indexes
based on the computed tomography angiographies in 10 patients who underwent a
mandible reconstruction with a free fibula flap and compared the results with
clinical outcome. RESULTS: In one case the flap was lost, because of thrombosis
in the donor vein. This patient presented superficial varicose veins of both
lower extremities. Peroneal vein diameters in this patient ranged from 5,05 mm to
6,68 mm and were higher than in patients without complications. The peroneal
artery-vein index in the patient with thrombosis ranged from 0,37 to 0,50 with
median 0,40 and was lower than in patients without complications. CONCLUSIONS:
High disproportion between peroneal artery and concomitant veins might be a
potential risk factor of the occurrence of venal thrombosis. Detailed
perioperative examination of peroneal veins in patients with varicosities should
be considered.
PMID- 27499516
TI - Visible tumor surface response to physical plasma and apoptotic cell kill in head
and neck cancer.
AB - The aim of the study was to learn, whether clinical application of cold
atmospheric pressure plasma (CAP) is able to cause (i) visible tumor surface
effects and (ii) apoptotic cell kill in squamous cell carcinoma and (iii) whether
CAP-induced visible tumor surface response occurs as often as CAP-induced
apoptotic cell kill. Twelve patients with advanced head and neck cancer and
infected ulcerations received locally CAP followed by palliative treatment. Four
of them revealed tumor surface response appearing 2 weeks after intervention. The
tumor surface response expressed as a flat area with vascular stimulation (type
1) or a contraction of tumor ulceration rims forming recesses covered with scabs,
in each case surrounded by tumor tissue in visible progress (type 2). In
parallel, 9 patients with the same kind of cancer received CAP before radical
tumor resection. Tissue specimens were analyzed for apoptotic cells. Apoptotic
cells were detectable and occurred more frequently in tissue areas previously
treated with CAP than in untreated areas. Bringing together both findings and
placing side by side the frequency of clinical tumor surface response and the
frequency of analytically proven apoptotic cell kill, detection of apoptotic
cells is as common as clinical tumor surface response. There was no patient
showing signs of an enhanced or stimulated tumor growth under influence of CAP.
CAP was made applicable by a plasma jet, kINPen((r)) MED (neoplas tools GmbH,
Greifswald, Germany).
PMID- 27499517
TI - Results of the 2-Year Ocriplasmin for Treatment for Symptomatic Vitreomacular
Adhesion Including Macular Hole (OASIS) Randomized Trial.
AB - PURPOSE: The Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion
Including Macular Hole (OASIS) trial was designed to evaluate the long-term
efficacy and safety profile of ocriplasmin for the treatment of symptomatic
vitreomacular adhesion (VMA)/vitreomacular traction, including full-thickness
macular hole (FTMH). DESIGN: Phase 3b, randomized, sham-controlled, double
masked, multicenter clinical trial. PARTICIPANTS: Sample size was 220 subjects
(146 ocriplasmin, 74 sham) randomized in a 2:1 ratio to receive intravitreal
ocriplasmin 0.125 mg or sham injection. METHODS: The trial involved 12 visits
over 24-months. Inclusion criteria included presence of VMA and best-corrected
visual acuity (BCVA) of 20/32 or worse in the study eye. Exclusion criteria
included FTMH >400 MUm, presence of epiretinal membrane (ERM), and aphakia in the
study eye. MAIN OUTCOME MEASURES: The primary efficacy end point was the
proportion of subjects with pharmacologic VMA resolution at day 28. Secondary
efficacy end points were assessed at month 24 and included proportion of subjects
with BCVA gain from baseline, nonsurgical FTMH closure, vitrectomy, and Visual
Function Questionnaire 25 (VFQ-25) outcomes. RESULTS: The OASIS trial met its
primary end point with pharmacologic VMA resolution at day 28 being significantly
higher in the ocriplasmin group (41.7%) compared with the sham group (6.2%). The
treatment effect was maintained until study end. In the ocriplasmin group,
pharmacologic VMA resolution at day 28 was higher in subgroups with the following
baseline characteristics compared with the complementary subgroups without them:
presence of focal VMA, presence of FTMH, absence of ERM, and phakic lens status.
In the ocriplasmin group, 50.5% of subjects had a >=2-line improvement in BCVA
from baseline compared with 39.1% of subjects in the sham group. The nonsurgical
FTMH closure rate was 30.0% for the ocriplasmin group compared with 15.4% for the
sham group. All other secondary end points also favored ocriplasmin over sham.
Regarding safety, most adverse events were mild to moderate, had a short onset
time, and were transient, with no new safety signals identified. CONCLUSIONS: The
OASIS trial demonstrates the long-term efficacy and safety of ocriplasmin,
providing improved resolution of symptomatic VMA compared with previous phase 3
trials with no additional safety signals identified.
PMID- 27499518
TI - Biomechanical evaluation of two arthroscopic techniques for biceps tenodesis:
triple loop suture versus simple suture.
AB - BACKGROUND: Several techniques and procedures have been described to treat long
head of the biceps pathology; however, tenodesis and tenotomy are the 2 most
common procedures performed. This study evaluated the initial fixation strength
of the biceps tenodesis triple loop suture (TLS) technique and compared it with
that of the simple suture technique (SST). METHODS: Twenty fresh frozen cadaveric
human shoulders (humeral head and neck with attached biceps tendons) were
harvested. The biceps tendon was tenotomized proximally before reattachment to
the bicipital groove of the matching humerus using suture anchors. Tenodesis was
performed using the SST or the TLS technique. Specimens were tested
biomechanically for load to failure, stress, and stiffness. The mechanism of
failure was evaluated and compared between the 2 suture techniques. RESULTS:
Maximal load to failure was significantly greater using the TLS technique (122.2
+/- 26.73 N) than the SST (46.12 +/- 14.37 N, P < .001). There was no difference
in the mean stiffness (SST: 7.33 +/- 4.41 N/mm, TLS: 7.46 N/mm +/- 2.67, P =
.94). The failure mechanism in all SST samples occurred by suture cutout through
the longitudinal fibers of the tendon. In all TLS samples, the failure occurred
by suture slippage. CONCLUSION: This study demonstrated superior load to failure
of the TLS compared with the SST technique for biceps tenodesis. Furthermore,
this study provides the first description of the TLS technique as a possible
application in biceps tenodesis. Clinical application of the TLS must be
carefully considered, because although it achieved a superior biomechanical
profile, experience with this stitch is limited.
PMID- 27499519
TI - Adoption of Robotic vs Fluoroscopic Guidance in Total Hip Arthroplasty: Is
Acetabular Positioning Improved in the Learning Curve?
AB - BACKGROUND: Acetabulum positioning affects dislocation rates, component
impingement, bearing surface wear rates, and need for revision surgery. Novel
techniques purport to improve the accuracy and precision of acetabular component
position, but may have a significant learning curve. Our aim was to assess
whether adopting robotic or fluoroscopic techniques improve acetabulum
positioning compared to manual total hip arthroplasty (THA) during the learning
curve. METHODS: Three types of THAs were compared in this retrospective cohort:
(1) the first 100 fluoroscopically guided direct anterior THAs (fluoroscopic
anterior [FA]) done by a surgeon learning the anterior approach, (2) the first
100 robotic-assisted posterior THAs done by a surgeon learning robotic-assisted
surgery (robotic posterior [RP]), and (3) the last 100 manual posterior (MP) THAs
done by each surgeon (200 THAs) before adoption of novel techniques. Component
position was measured on plain radiographs. Radiographic measurements were taken
by 2 blinded observers. The percentage of hips within the surgeons' "target zone"
(inclination, 30 degrees -50 degrees ; anteversion, 10 degrees -30 degrees ) was
calculated, along with the percentage within the "safe zone" of Lewinnek
(inclination, 30 degrees -50 degrees ; anteversion, 5 degrees -25 degrees ) and
Callanan (inclination, 30 degrees -45 degrees ; anteversion, 5 degrees -25
degrees ). Relative risk (RR) and absolute risk reduction (ARR) were calculated.
Variances (square of the standard deviations) were used to describe the
variability of cup position. RESULTS: Seventy-six percentage of MP THAs were
within the surgeons' target zone compared with 84% of FA THAs and 97% of RP THAs.
This difference was statistically significant, associated with a RR reduction of
87% (RR, 0.13 [0.04-0.40]; P < .01; ARR, 21%; number needed to treat, 5) for RP
compared to MP THAs. Compared to FA THAs, RP THAs were associated with a RR
reduction of 81% (RR, 0.19 [0.06-0.62]; P < .01; ARR, 13%; number needed to
treat, 8). Variances were lower for acetabulum inclination and anteversion in RP
THAs (14.0 and 19.5) as compared to the MP (37.5 and 56.3) and FA (24.5 and 54.6)
groups. These differences were statistically significant (P < .01). CONCLUSION:
Adoption of robotic techniques delivers significant and immediate improvement in
the precision of acetabular component positioning during the learning curve.
While fluoroscopy has been shown to be beneficial with experience, a learning
curve exists before precision improves significantly.
PMID- 27499520
TI - Body Mass Index Class Is Independently Associated With Health-Related Quality of
Life After Primary Total Hip Arthroplasty: An Institutional Registry-Based Study.
AB - BACKGROUND: The purpose of this study was to compare the health-related quality
of life (HRQoL) of patients across World Health Organization (WHO) body mass
index (BMI) classes before and after total hip arthroplasty (THA). METHODS:
Patients with end-stage hip osteoarthritis who received elective primary
unilateral THA were identified through an institutional registry and categorized
based on the World Health Organization BMI classification. Age, sex, laterality,
year of surgery, and Charlson-Deyo comorbidity index were recorded. The primary
outcome was the EQ-5D-3L index and visual analog scale (EQ-VAS) scores at 2 years
postoperatively. Inferential statistics and regression analyses were performed to
determine associations between BMI classes and HRQoL. RESULTS: EQ-5D-3L scores at
baseline and at 2 years were statistically different across BMI classes, with
higher EQ-VAS and index scores in patients with lower BMI. There was no
difference observed for the 2-year change in EQ-VAS scores, but there was a
statistically greater increase in index scores for more obese patients. In the
regression analyses, there were statistically significant negative effect
estimates for EQ-VAS and index scores associated with increasing BMI class.
CONCLUSION: BMI class is independently associated with lower HRQoL scores 2 years
after primary THA. While absolute scores in obese patients were lower than in
nonobese patients, obese patients enjoyed more positive changes in EQ-5D index
scores after THA. These results may provide the most detailed information on how
BMI influences HRQoL before and after THA, and they are relevant to future
economic decision analyses on the topic.
PMID- 27499522
TI - Changes in gene expression profiles in patients with pulmonary arterial
hypertension associated with scleroderma treated with tadalafil.
AB - OBJECTIVE: Pulmonary arterial hypertension (PAH) is one of the most devastating
complications in scleroderma (SSc) patients and has a poorer outcome than other
PAH subgroups. Tadalafil (Adcirca(r)) is a phosphodiesterase-5 inhibitor (PDE5-I)
approved by the FDA for treatment of PAH; however, its effectiveness specifically
in SSc-PAH patients is unclear. We investigated whether there were differences in
gene expression associated with 16 weeks of treatment with tadalafil and, if so,
whether these changes differed with respect to treatment outcome. METHODS: We
enrolled 10 SSc-PAH subjects who were naive to PDE5-I treatment, profiled gene
expression in whole blood prior to and following treatment with tadalafil,
measured changes in genomic profiles before and after treatment with tadalafil,
and correlated them with changes in clinical outcomes, such as cardiopulmonary
hemodynamics, six-min walk distance (6MWD), Borg Dyspnea Index (BDI), NYHA/WHO
functional class (FC), B-type natriuretic peptide (BNP), and cardiac magnetic
resonance imaging (cMRI). RESULTS: Genes associated with IL-12 signaling and
extracellular matrix maintenance were coordinately up- or down-regulated with
treatment, respectively, across all subjects. Interestingly, we found that genes
encoding voltage-gated potassium channels and genes related to innate immunity
were coordinately up-regulated in subjects who improved with tadalafil treatment
compared to those patients who did not. In contrast, up-regulation of Golgi
related gene sets was associated with clinical worsening during the treatment
period. CONCLUSION: The results of this pilot study suggest that outcomes of SSc
PAH patients treated with tadalafil are associated with specific changes in gene
expression and biological pathways.
PMID- 27499524
TI - Corrigendum to "Trajectories of changes over twelve years in the health status of
Canadians from late middle age" [Exp. Gerontol. 47/12 (2012) 893-899].
PMID- 27499523
TI - Transforming Growth Factor beta Drives Hemogenic Endothelium Programming and the
Transition to Hematopoietic Stem Cells.
AB - Hematopoietic stem cells (HSCs) are self-renewing multipotent stem cells that
generate mature blood lineages throughout life. They, together with hematopoietic
progenitor cells (collectively known as HSPCs), emerge from hemogenic endothelium
in the floor of the embryonic dorsal aorta by an endothelial-to-hematopoietic
transition (EHT). Here we demonstrate that transforming growth factor beta
(TGFbeta) is required for HSPC specification and that it regulates the expression
of the Notch ligand Jagged1a in endothelial cells prior to EHT, in a striking
parallel with the epithelial-to-mesenchymal transition (EMT). The requirement for
TGFbeta is two fold and sequential: autocrine via Tgfbeta1a and Tgfbeta1b
produced in the endothelial cells themselves, followed by a paracrine input of
Tgfbeta3 from the notochord, suggesting that the former programs the hemogenic
endothelium and the latter drives EHT. Our findings have important implications
for the generation of HSPCs from pluripotent cells in vitro.
PMID- 27499525
TI - Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship
Mathematical Modeling.
AB - Mathematical modeling is a valuable methodology used to study healthcare
epidemiology and antimicrobial stewardship, particularly when more traditional
study approaches are infeasible, unethical, costly, or time consuming. We focus
on 2 of the most common types of mathematical modeling, namely compartmental
modeling and agent-based modeling, which provide important advantages-such as
shorter developmental timelines and opportunities for extensive experimentation
over observational and experimental approaches. We summarize these advantages and
disadvantages via specific examples and highlight recent advances in the
methodology. A checklist is provided to serve as a guideline in the development
of mathematical models in healthcare epidemiology and antimicrobial stewardship.
Infect Control Hosp Epidemiol 2016;1-7.
PMID- 27499521
TI - The Power of Human Protective Modifiers: PLS3 and CORO1C Unravel Impaired
Endocytosis in Spinal Muscular Atrophy and Rescue SMA Phenotype.
AB - Homozygous loss of SMN1 causes spinal muscular atrophy (SMA), the most common and
devastating childhood genetic motor-neuron disease. The copy gene SMN2 produces
only ~10% functional SMN protein, insufficient to counteract development of SMA.
In contrast, the human genetic modifier plastin 3 (PLS3), an actin-binding and
bundling protein, fully protects against SMA in SMN1-deleted individuals carrying
3-4 SMN2 copies. Here, we demonstrate that the combinatorial effect of suboptimal
SMN antisense oligonucleotide treatment and PLS3 overexpression-a situation
resembling the human condition in asymptomatic SMN1-deleted individuals-rescues
survival (from 14 to >250 days) and motoric abilities in a severe SMA mouse
model. Because PLS3 knockout in yeast impairs endocytosis, we hypothesized that
disturbed endocytosis might be a key cellular mechanism underlying impaired
neurotransmission and neuromuscular junction maintenance in SMA. Indeed, SMN
deficit dramatically reduced endocytosis, which was restored to normal levels by
PLS3 overexpression. Upon low-frequency electro-stimulation, endocytotic FM1-43
(SynaptoGreen) uptake in the presynaptic terminal of neuromuscular junctions was
restored to control levels in SMA-PLS3 mice. Moreover, proteomics and biochemical
analysis revealed CORO1C, another F-actin binding protein, whose direct binding
to PLS3 is dependent on calcium. Similar to PLS3 overexpression, CORO1C
overexpression restored fluid-phase endocytosis in SMN-knockdown cells by
elevating F-actin amounts and rescued the axonal truncation and branching
phenotype in Smn-depleted zebrafish. Our findings emphasize the power of genetic
modifiers to unravel the cellular pathomechanisms underlying SMA and the power of
combinatorial therapy based on splice correction of SMN2 and endocytosis
improvement to efficiently treat SMA.
PMID- 27499526
TI - Coral reef health response to chronic and acute changes in water quality in St.
Thomas, United States Virgin Islands.
AB - It is suspected that land cover alteration on the southern coast of St. Thomas,
USVI has increased runoff, degrading nearshore water quality and coral reef
health. Chronic and acute changes in water quality, sediment deposition, and
coral health metrics were assessed in three zones based upon perceived degree of
human influence. Chlorophyll (p<0.0001) and turbidity (p=0.0113) were
significantly higher in nearshore zones and in the high impact zone during heavy
precipitation. Net sediment deposition and terrigenous content increased in
nearshore zones during periods of greater precipitation and port activity.
Macroalgae overgrowth significantly increased along a gradient of decreasing
water quality (p<0.0001). Coral bleaching in all zones peaked in November with a
regional thermal stress event (p<0.0001). However, mean bleaching prevalence was
significantly greater in the most impacted zone compared to the offshore zone
(p=0.0396), suggesting a link between declining water quality and bleaching
severity.
PMID- 27499527
TI - The impact of oral care on oral health status and prevention of ventilator
associated pneumonia in critically ill patients.
AB - BACKGROUND: Ventilator-associated pneumonia is one of the most common nosocomial
infections which increase mortality rate and length stay of hospitalisation. Oral
care would not only improve patient's oral health and well-being, but it can also
reduce the incidence rate of ventilator-associated pneumonia. OBJECTIVES: The
objective of this study was to identify the impact of oral care practices on oral
health status of patients in intensive care unit and the incidence rate of
ventilator-associated pneumonia. METHODS: This clinical trial recruited 100
participants who were randomly assigned to a control group (receiving oral care
by nurses) and an intervention group (receiving systematic care by the
researcher) during 2015-2016. Beck Oral Assessment Scale was used to determine
the required number of times for receiving oral care with regard to patient's
oral health in the intervention group. Each care included adjusting endotracheal
tube cuff pressure, brushing with toothpaste, using antiseptics and moistening
the lips. The oral cavity was examined using BOAS and Mucosal-Plaque Score, and
Clinical Pulmonary Infection Score was used for detecting pneumonia. RESULTS: The
BOAS scoring showed significant differences between the two groups from the first
to fifth day (P<0.001). The mucosal-plaque index was significantly different
between the two groups from the third day to fifth day (P<0.001). The incidence
rate of pneumonia on the third and fifth day was 10% (5) and 14% (7) in the
control group, and 4% (2) and 10% (5) in the intervention group, respectively.
The Fisher test did not show significant difference (P=0.538), however, the
incidence rate in the intervention group reduced compared with the control group.
CONCLUSION: Although following a systematic oral care program could not
significantly decrease the incidence of ventilator-associated pneumonia in
critically ill patients compared to the conventional oral care practices, it
significantly improved the oral health and mucosal-plaque index.
PMID- 27499528
TI - Structure-Based Identification of a Potent Inhibitor Targeting Stp1-Mediated
Virulence Regulation in Staphylococcus aureus.
AB - The increasing threats of antibiotic resistance urge the need for developing new
strategies against bacterial infections. Targeting eukaryotic-like Ser/Thr
phosphatase Stp1-mediated virulence regulation represents a promising approach
for combating staphylococcal infection yet to be explored. Here, we report the
2.32-A resolution crystal structure of Stp1. Stp1 binds an unexpected fourth
metal ion, which is important for Stp1's enzymatic activity as demonstrated by
amino acid substitution studies. Inspired by the structural details of Stp1, we
identified a potent and selective Stp1 inhibitor, aurintricarboxylic acid (ATA).
Transcriptome analysis and biochemical studies supported Stp1 as the target of
ATA inhibition within the pathogen, preventing upregulation of virulence genes.
Notably, ATA did not affect in vitro growth of Staphylococcus aureus, while
simultaneously attenuating staphylococcal virulence in mice. Our findings
demonstrate that ATA is a potent anti-virulence compound against staphylococcal
infection, laying the foundation for further developing new scaffolds for Stp1
targeted small molecules.
PMID- 27499531
TI - Author Reply.
PMID- 27499530
TI - Global Cysteine-Reactivity Profiling during Impaired Insulin/IGF-1 Signaling in
C. elegans Identifies Uncharacterized Mediators of Longevity.
AB - In the nematode Caenorhabditis elegans, inactivating mutations in the insulin/IGF
1 receptor, DAF-2, result in a 2-fold increase in lifespan mediated by DAF-16, a
FOXO-family transcription factor. Downstream protein activities that directly
regulate longevity during impaired insulin/IGF-1 signaling (IIS) are poorly
characterized. Here, we use global cysteine-reactivity profiling to identify
protein activity changes during impaired IIS. Upon confirming that cysteine
reactivity is a good predictor of functionality in C. elegans, we profiled
cysteine-reactivity changes between daf-2 and daf-16;daf-2 mutants, and
identified 40 proteins that display a >2-fold change. Subsequent RNAi-mediated
knockdown studies revealed that lbp-3 and K02D7.1 knockdown caused significant
increases in lifespan and dauer formation. The proteins encoded by these two
genes, LBP-3 and K02D7.1, are implicated in intracellular fatty acid transport
and purine metabolism, respectively. These studies demonstrate that cysteine
reactivity profiling can be complementary to abundance-based transcriptomic and
proteomic studies, serving to identify uncharacterized mediators of C. elegans
longevity.
PMID- 27499532
TI - Editorial Comment.
PMID- 27499529
TI - Stabilizing the Hsp70-Tau Complex Promotes Turnover in Models of Tauopathy.
AB - Heat shock protein 70 (Hsp70) is a chaperone that normally scans the proteome and
initiates the turnover of some proteins (termed clients) by linking them to the
degradation pathways. This activity is critical to normal protein homeostasis,
yet it appears to fail in diseases associated with abnormal protein accumulation.
It is not clear why Hsp70 promotes client degradation under some conditions,
while sparing that protein under others. Here, we used a combination of chemical
biology and genetic strategies to systematically perturb the affinity of Hsp70
for the model client, tau. This approach revealed that tight complexes between
Hsp70 and tau were associated with enhanced turnover while transient interactions
favored tau retention. These results suggest that client affinity is one
important parameter governing Hsp70-mediated quality control.
PMID- 27499533
TI - Genetic diversity and distribution of bradyrhizobia nodulating peanut in acid
neutral soils in Guangdong Province.
AB - To reveal the genetic diversity and geographic distribution of peanut (Arachis
hypogaea L.) rhizobia in Guangdong Province, one of the main peanut producing
regions in China, 216 bradyrhizobial isolates were trapped by peanut plants
inoculated with soil samples (pH 4.7-7.4) collected from ten sites in Guangdong.
Based on BOX-PCR fingerprinting analysis, 71 representative isolates were
selected for sequence analyses of ribosomal IGS, recA, atpD and symbiotic gene
nodA. As a result, 22 genospecies were detected in the peanut rhizobia, including
eight minor groups or single strains corresponding to Bradyrhizobium
diazoefficiens, B. japonicum, B. yuanmingense, B. arachidis, B. guangdongense, B.
guangxiense, B. iriomotense and B. liaoningense, as well as 14 novel
Bradyrhizobium genospecies covering the majority of isolates. Five symbiotic
clusters were obtained based on the phylogenetic relationships of nodA genes,
related to the soybean-nodulating or peanut-nodulating reference strains.
Biogeographic patterns, which were mainly correlated with potassium content and
pH, were detected in the peanut bradyrhizobial community in Guangdong Province.
These findings enriched the diversity of peanut rhizobia, and added the K content
as a special determinant for peanut rhizobial distribution in acid soils.
PMID- 27499534
TI - 61-Year-Old Man With Right Knee Pain and Chronic Anemia.
PMID- 27499536
TI - Biologics in practice: A unique opportunity for allergist/immunologist expertise.
PMID- 27499535
TI - Serum Potassium, Mortality, and Kidney Outcomes in the Atherosclerosis Risk in
Communities Study.
AB - OBJECTIVES: To investigate the association between serum potassium, mortality,
and kidney outcomes in the general population and whether potassium-altering
medications modify these associations. PATIENTS AND METHODS: We studied 15,539
adults in the Atherosclerosis Risk in Communities Study. Cox proportional hazard
regression was used to investigate the association of serum potassium at baseline
(1987-1989), evaluated categorically (hypokalemia, <3.5 mmol/L; normokalemia,
>=3.5 and <5.5 mmol/L; hyperkalemia, >=5.5 mmol/L) and continuously using linear
spline terms (knots at 3.5 and 5.5 mmol/L), with mortality, sudden cardiac death,
incident chronic kidney disease, and end-stage renal disease. The end date of
follow-up for all outcomes was December 31, 2012. We also evaluated whether
classes of potassium-altering medications modified the association between serum
potassium and adverse outcomes. RESULTS: Overall, 413 (2.7%) of the participants
had hypokalemia and 321 (2.1%) had hyperkalemia. In a fully adjusted model,
hyperkalemia was significantly associated with mortality (hazard ratio, 1.24; 95%
CI, 1.04-1.49) but not sudden cardiac death, chronic kidney disease, or end-stage
renal disease. Hypokalemia as a categorical variable was not associated with any
outcome; however, associations of hypokalemia with all-cause mortality and kidney
outcomes were observed among those who were not taking potassium-wasting
diuretics (all P for interaction, <.001). CONCLUSIONS: Higher values of serum
potassium were associated with a higher risk of mortality in the general
population. Lower levels of potassium were associated with adverse kidney
outcomes and mortality among participants not taking potassium-wasting diuretics.
PMID- 27499537
TI - The immunology of asthma: Asthma phenotypes and their implications for
personalized treatment.
AB - OBJECTIVES: To review current thinking regarding the role of personalized
phenotype-driven as opposed to broad guideline-based therapies in asthma and to
speculate on the relative contributions of innate (lung) and adaptive (T and B
lymphocyte) roles in asthma pathogenesis. DATA SOURCES: PubMed literature review.
STUDY SELECTIONS: Articles pertaining to asthma pathogenesis, with emphasis on
those that included biotherapeutic interventions. RESULTS: Current methods allow
asthma to be divided into phenotypes characterized by the presence or absence of
eosinophilic inflammation. Corticosteroids are likely to be only effective in the
context of eosinophilic inflammation. Similarly, interventions with
biotherapeutic agents currently available or in development have efficacious only
when administered to patients with asthma of relevant phenotypes. CONCLUSION: The
availability of biotherapeutic agents that target IgE, interleukin (IL) 5, and,
in the near future, IL-13 is an exciting vindication of molecular medicine.
However, these biotherapeutic agents are only effective when targeted to patients
with specific asthma phenotypes. In Promising biotherapeutic targets are the
airway epithelial-derived cytokines IL-25, IL-33, and thymic stromal
lymphopoietin. Targeting these lung epithelial-derived mediators, instead of
products of the adaptive immune system, may be more likely to improve day-to-day
asthma symptoms in contrast to agents that target the adaptive immune system,
approaches that primarily act to ameliorate asthma exacerbations.
PMID- 27499538
TI - Hypersensitivity and immunologic reactions to biologics: opportunities for the
allergist.
AB - OBJECTIVE: There has been a great expanse in the use of biological agents during
the past decade. However, there are significant differences between biologics and
typical pharmaceutical drugs. This review focuses on 3 separate types of adverse
reactions to biologics, namely high cytokine reactions, hypersensitivity
reactions, and secondary immunodeficiency. DATA SOURCES: A PubMed literature
search restricted to the previous 10 years using combinations of search terms,
including omalizumab, rituximab, TGN1412, biologic agent, anaphylaxis,
hypogammaglobulinemia, desensitization, and cytokine storm, was performed. The
results were manually filtered to identify relevant articles with additional
references identified from bibliographies. STUDY SELECTION: Reports were selected
for TGN1412 cytokine storm, omalizumab anaphylaxis and desensitization, rituximab
induced hypogammaglobulinemia, rituximab anaphylaxis and serum sickness, and
monoclonal antibody desensitization. RESULTS: A phase 1 clinical trial using a
humanized anti-CD28 monoclonal antibody (TGN1412) caused severe cytokine storm
reactions in all 6 subjects, resulting in multiorgan failure. Omalizumab has been
reported to cause anaphylaxis in fewer than 0.1% of patients, many with delayed
reactions. The mechanism for this anaphylactic reaction is unclear. Rituximab has
been associated with hypogammaglobulinemia, serum sickness-like reactions, and
anaphylaxis. Rapid drug desensitizations to monoclonal antibodies, including
rituximab, suspected of causing immunoglobulin E-mediated reactions have been
found to be generally safe and effective. CONCLUSION: Hypersensitivity reactions
and immune dysregulation from biologic agents are not rare. The allergist and
immunologist should be involved in managing these patients for optimal care.
PMID- 27499539
TI - Characterization of asthma endotypes: implications for therapy.
AB - OBJECTIVE: To describe the concept of precision medicine in treating severe
asthma and the utility of relevant biomarkers. DATA SOURCES: PubMed was searched
for published articles on human clinical trials using biologics for T-helper type
2 cell (TH2)-low and TH2-high asthma. STUDY SELECTIONS: Studies were selected if
they were double-masked, randomized, placebo-controlled trials published in peer
reviewed journals and relevant to the topic. RESULTS: Multiple immune response
modifiers have been evaluated in TH2-high asthma geared at blocking interleukin
(IL)-5, IL-13, immunoglobulin E, prostaglandin D2, and other pathways. Currently,
3 immune response modifiers approved by the Food and Drug Administration are
available for treating severe TH2-high asthma (1 anti-immunoglobulin E and 2 anti
IL-5 monoclonal antibodies) and other TH2-high therapies are in various stages of
clinical development. Thus far, many of the TH2-high therapies have shown better
efficacy when certain biomarkers are elevated, especially blood eosinophils. The
TH2-low endotype does not have any readily available point-of-care biomarkers, so
TH2-low asthma is often diagnosed based on a lack of TH2-high biomarkers. These
patients tend to have greater resistance to steroids and the development of
therapies has lagged behind that for TH2-high asthma. CONCLUSION: Two major
endotypes for asthma have been described, TH2-high, manifested by increased
eosinophils in the sputum and airways of patients, and TH2-low, with increased
neutrophils or a pauci-granulocytic profile. Using these classifications and
specific biomarkers has led to promising new therapeutics, especially for TH2
high asthma.
PMID- 27499540
TI - The transforming power of proximity food challenges.
PMID- 27499542
TI - Mobile health applications in clinical practice: pearls, pitfalls, and key
considerations.
PMID- 27499541
TI - Basic science for the clinician: Mechanisms of sublingual and subcutaneous
immunotherapy.
AB - OBJECTIVE: To discuss the general immunologic changes that occur during
immunotherapy, focusing on the differences between subcutaneous immunotherapy
(SCIT) and sublingual immunotherapy (SLIT). DATA SOURCES: PubMed literature
review. STUDY SELECTIONS: Articles pertaining to SCIT and SLIT, with specific
emphasis on those that included immune mechanistic studies. RESULTS: Both SCIT
and SLIT are characterized by the induction of regulatory B and T cells,
decreased allergen-specific T-cell proliferation, a shift from a TH2 to TH1
cytokine milieu and from an IgE to an IgG4/IgA antibody response. These changes
are accompanied by clinical improvement in symptoms. CONCLUSION: Immunotherapy
using allergen extracts administered via both subcutaneous and sublingual
approaches have demonstrated efficacy in the treatment of allergic
rhinoconjunctivitis and other allergic conditions. There are subtle differences
between the approaches, and understanding these differences may help clinicians
select a preferred route of therapy for particular patients or allergens,
depending on the immune response that is being targeted.
PMID- 27499543
TI - Evaluation of the association between sensitization to common inhalant fungi and
poor asthma control.
AB - BACKGROUND: Fungi are well-known airborne allergens that are predisposing
environmental factors to asthma. Few comparative studies have evaluated
sensitization to common inhalant fungi in relation to poor asthma control in
patients with asthma. OBJECTIVE: To evaluate the association between
sensitization to individual fungi and asthma control and elucidate the
characteristics of patients with poorly controlled asthma sensitized to fungi.
METHODS: This cross-sectional study was performed at Showa University Hospital
between September 2014 and December 2014. The specific IgE levels for several
major aeroallergens, including house dust mites, Japanese cedar, various types of
pollen, furry animals, or insects, were measured with a fluorescent enzyme
immunoassay in 160 patients with adult asthma. RESULTS: Fungal sensitization was
predominant in men with asthma, and it was associated with poor asthma control.
Sensitization to house dust mites, Japanese cedar, pollen, furry animals, or
insects was not associated with poor asthma control. Logistic regression analyses
revealed that patients sensitized to Aspergillus and Penicillium had a
significantly increased risk of poor asthma control. More Penicillium IgE
positive patients were men and pet owners compared with Penicillium IgE-negative
patients; in addition, Penicillium IgE-positive patients had higher total IgE
levels. The Asthma Control Test level was significantly higher in Penicillium IgE
positive patients than in Penicillium IgE-negative patients. However, there were
no differences in fractional exhaled nitric oxide, forced vital capacity, and
forced expiratory volume in 1 second. Finally, sensitization to Aspergillus,
Cladosporium, and Trichophyton were positively correlated with sensitization to
Penicillium. CONCLUSION: Sensitization to fungi is predominant in men, and it is
associated with poor asthma control. In particular, sensitization to Penicillium
and Aspergillus is a risk factor for asthma severity. These results have
potential relevance in asthma management.
PMID- 27499545
TI - Erratum.
PMID- 27499544
TI - Allergic contact dermatitis to balsam of Peru.
PMID- 27499546
TI - The Best of Both Worlds: The Benefits of Open-specialized and Closed-diverse
Syndication Networks for New Ventures' Success.
AB - Open networks give actors non-redundant information that is diverse, while closed
networks offer redundant information that is easier to interpret. Integrating
arguments about network structure and the similarity of actors' knowledge, we
propose two types of network configurations that combine diversity and ease of
interpretation. Closed-diverse networks offer diversity in actors' knowledge
domains and shared third-party ties to help in interpreting that knowledge. In
open-specialized networks, structural holes offer diversity, while shared
interpretive schema and overlap between received information and actors' prior
knowledge help in interpreting new information without the help of third parties.
In contrast, actors in open-diverse networks suffer from information overload due
to the lack of shared schema or overlapping prior knowledge for the
interpretation of diverse information, and actors in closed-specialized networks
suffer from overembeddedness because they cannot access diverse information.
Using CrunchBase data on early-stage venture capital investments in the U.S.
information technology sector, we test the effect of investors' social capital on
the success of their portfolio ventures. We find that ventures have the highest
chances of success if their syndicating investors have either open-specialized or
closed-diverse networks. These effects are manifested beyond the direct effects
of ventures' or investors' quality and are robust to controlling for the
possibility that certain investors could have chosen more promising ventures at
the time of first funding.
PMID- 27499547
TI - An Example of an Improvable Rao-Blackwell Improvement, Inefficient Maximum
Likelihood Estimator, and Unbiased Generalized Bayes Estimator.
AB - The Rao-Blackwell theorem offers a procedure for converting a crude unbiased
estimator of a parameter theta into a "better" one, in fact unique and optimal if
the improvement is based on a minimal sufficient statistic that is complete. In
contrast, behind every minimal sufficient statistic that is not complete, there
is an improvable Rao-Blackwell improvement. This is illustrated via a simple
example based on the uniform distribution, in which a rather natural Rao
Blackwell improvement is uniformly improvable. Furthermore, in this example the
maximum likelihood estimator is inefficient, and an unbiased generalized Bayes
estimator performs exceptionally well. Counterexamples of this sort can be useful
didactic tools for explaining the true nature of a methodology and possible
consequences when some of the assumptions are violated. [Received December 2014.
Revised September 2015.].
PMID- 27499548
TI - Can survival analyses detect hunting pressure in a highly connected species?
Lessons from straw-coloured fruit bats.
AB - Animal behaviour, social structure and population dynamics affect community
structure, interspecific interactions, and a species' resilience to harvesting.
Building on new life history information for the straw-coloured fruit bat
(Eidolon helvum) from multiple localities across Africa, we used survival
analyses based on tooth-cementum annuli data to test alternative hypotheses
relating to hunting pressure, demography and population connectivity. The
estimated annual survival probability across Africa was high (>= 0.64), but was
greatest in colonies with the highest proportion of males. This difference in sex
survival, along with age and sex capture biases and out-of-phase breeding across
the species' distribution, leads us to hypothesize that E. helvum has a complex
social structure. We found no evidence for additive mortality in heavily hunted
populations, with most colonies having high survival with constant risk of
mortality despite different hunting pressure. Given E. helvum's slow life history
strategy, similar survival patterns and rate among colonies suggest that local
movement and regional migration may compensate for local excess hunting, but
these were also not clearly detected. Our study suggests that spatio-temporal
data are necessary to appropriately assess the population dynamics and
conservation status of this and other species with similar traits.
PMID- 27499549
TI - Underlayer Effect on Perpendicular Magnetic Anisotropy in Co20Fe60B20?MgO Films.
AB - Perpendicular Magnetic Tunneling Junctions (pMTJs) with Ta?CoFeB?MgO have been
extensively studied in recent years. However, the effects of the underlayer on
the formation of the CoFeB perpendicular magnetic anisotropy (PMA) are still not
well understood. Here we report the results of our systematic use of a wide range
of elements (Ti, V, Cr, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Hf, Ta, W, Re, Os, Ir, Pt and
Au) encompassed by columns IVA, VA, VIA, VIIA and VIIIA of the periodic table as
the underlayer in a underlayer?Co20Fe60B20?MgO stack. Our goals were to survey
more elements which could conceivably create a PMA in CoFeB and thereby to
explore the mechanisms enabling these underlayers to enhance or create the PMA.
We found underlayer elements having both an outer shell of 4d electrons (Zr, Nb
Mo, and Pd) and 5d electrons (Hf, Ta, W, Re, Ir, and Pt) resulted in the
development of a PMA in the MgO-capped Co20Fe60B20. Hybridization between the 3d
electrons of the Fe or Co (in the Co20Fe60B20) at the interface with the 4d or 5d
electrons of the underlayer is thought to be the cause of the PMA development.
PMID- 27499550
TI - Effect of Using 2mm Voxels on Observer Performance for PET Lesion Detection.
AB - Positron emission tomography (PET) images are typically reconstructed with an in
plane pixel size of approximately 4mm for cancer imaging. The objective of this
work was to evaluate the effect of using smaller pixels on general oncologic
lesion-detection. A series of observer studies was performed using experimental
phantom data from the Utah PET Lesion Detection Database, which modeled whole
body FDG PET cancer imaging of a 92kg patient. The data comprised 24 scans over 4
days on a Biograph mCT time-of-flight (TOF) PET/CT scanner, with up to 23 lesions
(diam. 6-16mm) distributed throughout the phantom each day. Images were
reconstructed with 2.036mm and 4.073mm pixels using ordered-subsets expectation
maximization (OSEM) both with and without point spread function (PSF) modeling
and TOF. Detection performance was assessed using the channelized non-prewhitened
numerical observer with localization receiver operating characteristic (LROC)
analysis. Tumor localization performance and the area under the LROC curve were
then analyzed as functions of the pixel size. In all cases, the images with ~2mm
pixels provided higher detection performance than those with ~4mm pixels. The
degree of improvement from the smaller pixels was larger than that offered by PSF
modeling for these data, and provided roughly half the benefit of using TOF. Key
results were confirmed by two human observers, who read subsets of the test data.
This study suggests that a significant improvement in tumor detection performance
for PET can be attained by using smaller voxel sizes than commonly used at many
centers. The primary drawback is a 4-fold increase in reconstruction time and
data storage requirements.
PMID- 27499551
TI - Ontogenic differences in sexual size dimorphism across four plover populations.
AB - Sexual size dimorphism (SSD) among adults is commonly observed in animals and is
considered to be adaptive. However, the ontogenic emergence of SSD, i.e. the
timing of divergence in body size between males and females, has only recently
received attention. It is widely acknowledged that the ontogeny of SSD may differ
between species, but it remains unclear how variable the ontogeny of SSD is
within species. Kentish Plovers Charadrius alexandrinus and Snowy Plovers C.
nivosus are closely related wader species that exhibit similar, moderate (c. 4%),
male-biased adult SSD. To assess when SSD emerges we recorded tarsus length
variation among 759 offspring in four populations of these species. Tarsus length
of chicks was measured on the day of hatching and up to three times on recapture
before fledging. In one population (Mexico, Snowy Plovers), males and females
differed in size from the day of hatching, whereas growth rates differed between
the sexes in two populations (Turkey and United Arab Emirates, both Kentish
Plovers). In contrast, a fourth population (Cape Verde, Kentish Plovers) showed
no significant SSD in juveniles. Our results suggest that adult SSD can emerge at
different stages of development (prenatal, postnatal and post-juvenile) in
different populations of the same species. We discuss the proximate mechanisms
that may underlie these developmental differences.
PMID- 27499552
TI - 'Mortgaged lives': the biopolitics of debt and housing financialisation.
AB - The paper expands the conceptual framework within which we examine mortgage debt
by reconceptualising mortgages as a biotechnology: a technology of power over
life that forges an intimate relationship between global financial markets,
everyday life and human labour. Taking seriously the materiality of mortgage
contracts as a means of forging new embodied practices of financialisation, we
urge for the need to move beyond a policy- and macroeconomics-based analysis of
housing financialisation. We argue that more attention needs to be paid to how
funnelling land-related capital flows goes hand in hand with signing off
significant parts of future labour, decisionmaking capacity and well-being to
mortgage debt repayments. The paper offers two key insights. First, it
exemplifies how macroeconomic and policy changes could not have led to the
financialisation of housing markets without a parallel biopolitical process that
mobilised mortgage contracts to integrate the social reproduction of the
workforce into speculative global real-estate practices. Second, it expands the
framework of analysis of emerging literature on financialisation and
subjectification. Focusing on the mortgage defaults and evictions crisis in
Spain, we document how during Spain's 1997-2007 real-estate boom the promise of
mortgages as a means to optimise income and wealth enrolled livelihoods into
cycles of global financial and real-estate speculation, as home security and
future wealth became directly dependent on the fluctuations of financial
products, interest rates and capital accumulation strategies rooted in the built
environment. When, after 2008 unemployment escalated and housing prices
collapsed, mortgages became a punitive technology that led to at least 500 000
foreclosures and over 250 000 evictions in Spain.
PMID- 27499553
TI - Foraging choices of vampire bats in diverse landscapes: potential implications
for land-use change and disease transmission.
AB - In Latin America, the common vampire bat Desmodus rotundus is the primary
reservoir of rabies, a zoonotic virus that kills thousands of livestock annually
and causes sporadic and lethal human rabies outbreaks. The proliferation of
livestock provides an abundant food resource for this obligate blood-feeding
species that could alter its foraging behaviour and rabies transmission, but poor
understanding of the dietary plasticity of vampire bats limits understanding of
how livestock influences rabies risk.We analysed individual- and population-level
foraging behaviour by applying delta13C and delta15N stable isotope analysis to
hair samples from 183 vampire bats captured from nine colonies in Peru. We also
assessed the isotopic distributions of realized prey by analysing blood meals
extracted from engorged bats and samples collected from potential prey species.
In two adjacent but contrasting areas of the Amazon with scarce and abundant
livestock, we used questionnaires to evaluate the incidence of feeding on
humans.Population-level isotopic signatures suggested substantial among-site
variation in feeding behaviour, including reliance on livestock in some colonies
and feeding on combinations of domestic and wild prey in others. Isotopic
heterogeneity within bat colonies was among the largest recorded in vertebrate
populations, indicating that individuals consistently fed on distinct prey
resources and across distinct trophic levels. In some sites, isotopic values of
realized prey spanned broad ranges, suggesting that bats with intermediate
isotopic values could plausibly be dietary specialists rather than
generalists.Bayesian estimates of isotopic niche width varied up to ninefold
among colonies and were maximized where wildlife and livestock were present at
low levels, but declined with greater availability of livestock. In the Amazon,
the absence of livestock was associated with feeding on humans and wildlife.
Policy implications. We provide the first insights into the foraging behaviour of
vampire bats in habitats with common depredation on humans and show how vampire
bat foraging may respond to land-use change. Our results demonstrate risks of
rabies transmission from bats to other wildlife and are consistent with the
hypothesis that introducing livestock might reduce the burden of human rabies in
high-risk communities.
PMID- 27499554
TI - Father's Migration and Leaving the Parental Home in Rural Mozambique.
AB - Migration is an increasingly common demographic phenomenon and has important
implications for the well-being of family members left behind. Although extensive
research has examined the impact of parental labor migration on school-age
children, less is known about its effect on adolescents. In this study, the
authors used longitudinal survey data collected in rural Mozambique (N = 515) to
assess the association between father's migration and adolescent children's
leaving the parental home, an important component of the transition to adulthood.
The results showed that father's migration delays home-leaving for adolescent
girls and that these effects are not mediated by school enrollment. The results
for boys were inconclusive. The authors also found that remittances and longer
durations of paternal migration were negatively associated with the transition
out of the home. On the basis of the findings, they argue that father's migration
delays girls' marriage.
PMID- 27499555
TI - Resource Scarcity and Prescriptive Attitudes Generate Subtle, Intergenerational
Older-Worker Exclusion.
AB - Prior work describes specific, prescriptive resource tensions between
generations, comprising active Succession, passive Consumption, and symbolic
Identity (SCI; North & Fiske, 2013a, 2013b). The current paper focuses on how
these domains potentially drive intergenerational exclusion in work-related
networking and training spheres. Studies 1a-1c-each focusing on a different SCI
domain-manipulated perceived resource availability between generations, then
introduced a professional networking opportunity. Across studies, scarcity
reduced the likelihood of young participants' networking engagement with older
workers who violated SCI resource expectations. Study 2 impelled participants to
allocate scarce training resources among three similarly qualified but different
aged employees (younger, middle-aged, and older). Older workers received the
lowest such investment, particularly among younger participants-an effect driven
by Succession beliefs, per mediation analyses. Overall, the findings emphasize
resource tensions in driving older workers' subtle exclusion by younger
generations; minimizing such tensions will be critical for aging, increasingly
intergenerational workplaces.
PMID- 27499557
TI - Health and Greater Manchester in Historical Perspective.
AB - This article maps the history of health organisation across Greater Manchester
(GM), primarily since the Second World War, to show how against a continuing
backdrop of health inequalities, services have been driven (and constrained) by
the needs and the politics of each period. Defining 'success' as benefits for
patients the article identifies examples such as Salford's mental health services
(1950s and 1960s), public health in North Manchester (1970s and 1980s), the
creation of centres for diabetes, sickle-cell and thalassaemia (1980s) and the
formation of the Joint Health Unit in 2002. What this history shows is that over
the period the common factors influencing the 'success' of health organisation
across GM have been the championing of particular issues by multi-disciplinary
groups working across health and social care and stability in structures and
personnel.
PMID- 27499556
TI - Fossilization of melanosomes via sulfurization.
AB - Fossil melanin granules (melanosomes) are an important resource for inferring the
evolutionary history of colour and its functions in animals. The taphonomy of
melanin and melanosomes, however, is incompletely understood. In particular, the
chemical processes responsible for melanosome preservation have not been
investigated. As a result, the origins of sulfur-bearing compounds in fossil
melanosomes are difficult to resolve. This has implications for interpretations
of original colour in fossils based on potential sulfur-rich phaeomelanosomes.
Here we use pyrolysis gas chromatography mass spectrometry (Py-GCMS), fourier
transform infrared spectroscopy (FTIR) and time of flight secondary ion mass
spectrometry (ToF-SIMS) to assess the mode of preservation of fossil
microstructures, confirmed as melanosomes based on the presence of melanin,
preserved in frogs from the Late Miocene Libros biota (NE Spain). Our results
reveal a high abundance of organosulfur compounds and non-sulfurized fatty acid
methyl esters in both the fossil tissues and host sediment; chemical signatures
in the fossil tissues are inconsistent with preservation of phaeomelanin. Our
results reflect preservation via the diagenetic incorporation of sulfur, i.e.
sulfurization (natural vulcanization), and other polymerization processes.
Organosulfur compounds and/or elevated concentrations of sulfur have been
reported from melanosomes preserved in various invertebrate and vertebrate
fossils and depositional settings, suggesting that preservation through
sulfurization is likely to be widespread. Future studies of sulfur-rich fossil
melanosomes require that the geochemistry of the host sediment is tested for
evidence of sulfurization in order to constrain interpretations of potential
phaeomelanosomes and thus of original integumentary colour in fossils.
PMID- 27499558
TI - Orthogonalizing EM: A design-based least squares algorithm.
AB - We introduce an efficient iterative algorithm, intended for various least squares
problems, based on a design of experiments perspective. The algorithm, called
orthogonalizing EM (OEM), works for ordinary least squares and can be easily
extended to penalized least squares. The main idea of the procedure is to
orthogonalize a design matrix by adding new rows and then solve the original
problem by embedding the augmented design in a missing data framework. We
establish several attractive theoretical properties concerning OEM. For the
ordinary least squares with a singular regression matrix, an OEM sequence
converges to the Moore-Penrose generalized inverse-based least squares estimator.
For ordinary and penalized least squares with various penalties, it converges to
a point having grouping coherence for fully aliased regression matrices.
Convergence and the convergence rate of the algorithm are examined. Finally, we
demonstrate that OEM is highly efficient for large-scale least squares and
penalized least squares problems, and is considerably faster than competing
methods when n is much larger than p. Supplementary materials for this article
are available online.
PMID- 27499559
TI - From recreational to functional drug use: the evolution of drugs in American
higher education, 1960-2014.
AB - The increasing prevalence of so-called cognitive-enhancing drugs is well
documented in American higher education. There has been little historical
analysis, however, specifically exploring the role of postsecondary institutions
in this evolving drug narrative. This paper traces substance use and research
trends in American higher education over the past half-century, divided into
three eras defined by their disparate approaches to drug policy and public
health. Contextualised by historic events, shifting policies and epidemiological
data, this multidisciplinary analysis contends that functional, academically
oriented drug use is likely to continue rising on US campuses, while recreational
drug use will evolve and persist. As history provides a useful lens for
understanding the involvement of academe in the first era of drug concern in
America, ongoing innovations in medical and social science may be instructive to
help ensure that institutions respond judiciously in the present era of new drug
synthesis and drug policy recession.
PMID- 27499560
TI - Do Migrants Degrade Coastal Environments? Migration, Natural Resource Extraction
and Poverty in North Sulawesi, Indonesia.
AB - Recent literature on migration and the environment has identified key mediating
variables such as how migrants extract resources from the environment for their
livelihoods, the rate and efficiency of extraction, and the social and economic
context within which their extraction occurs. This paper investigates these
variables in a new ecological setting using data from coastal fishing villages in
North Sulawesi, Indonesia. We do not find as many differences between migrant and
non-migrant families regarding destructive fishing behavior, technology, and
investment as might have been expected from earlier theories. Instead, the
context and timing of migrant assimilation seems to be more important in
explaining apparent associations of migration and environmental impacts than
simply migrants themselves. This finding fits well with recent literature in the
field of international migration and immigrant incorporation.
PMID- 27499561
TI - Trust: The Missing Dimension in the Food Retail Transition in Thailand.
AB - Thailand has experienced dramatic growth of large national and international
modern food retailers, such as supermarkets, hypermarkets and convenience stores
in large cities and regional centres in the last two decades. Nevertheless, Thai
consumers continue to purchase perishables (fruits, vegetables and animal
products) from fresh markets (wet markets, talat sot) contradicting predictions
from analysts that modern food retail chains will rapidly replace fresh markets
as the preferred venue for purchasing all types of foods. This paper examines
trust in food retail systems as an under-explored dimension lying behind the
continued patronage by Thais of fresh markets to purchase perishable items. It
derives from a research program commenced in 2005 that includes fieldwork visits,
interviews and questionnaires. In the context of the Thai food retail transition,
we propose that trust affects relationships between consumers and (1) individual
fresh market-based vendors, (2) the food products sold at fresh markets and (3)
the food retail system more broadly. If fresh markets can be maintained in the
face of sustained pressure from modern national and international food retailers,
Thais will continue to use them. Meanwhile, trust is a relatively unrecognised
dimension that is supporting the continued existence of traditional food retail
formats.
PMID- 27499562
TI - Serious Psychological Distress Among African Americans: Findings from the
National Survey of American Life.
AB - Despite their low social standing, there remains a paucity of research on
psychological distress among African Americans. We use data from the 2001-2003
National Survey of American Life to explore a wide array of social and economic
predictors of psychological distress among African American adults ages 18 and
older, including previous incarceration, history of welfare receipt, and having a
family member who is either currently incarcerated or homeless. Younger age,
lower income, lower educational attainment, and lower self-rated health and
childhood health are associated with higher levels of psychological distress
among African Americans. We also find a strong association between higher levels
of material hardship, previous incarceration history, and the presence of a
family member who is either incarcerated or homeless and higher levels of
psychological distress. The findings highlight the importance of considering
unique types of social disadvantage experienced by African Americans living in a
highly stratified society.
PMID- 27499563
TI - Knowledge, attitudes and perceptions of nurses and nursing students towards
HIV/AIDS.
AB - OBJECTIVE: To describe attitudes, knowledge and perceptions of nurses and nursing
students towards the people who live with HIV/AIDS (PLWHA). METHODOLOGY:
Bibliographic study in which six electronic databases were searched using the key
words: "attitude", "knowledge", "nursing", perceptions", "HIV/AIDS". Publications
between 1998 and 2007 were considered. RESULTS: 560 articles limited by
scientific researches or ministerial reports membership were retrieved. Finally a
total of 38 publications were selected, the analysis showed that the level of
knowledge of nurses and nursing students about PLWHA is good and the attitudes
towards HIV/AIDS have improved over time. Nurses and nursing students have been
able to identify both positive and negative aspects in the PLWHA care personally
and professionally because there is a more favourable perception. CONCLUSION:
There are few studies in Latin America and Chile that study the attitudes and
knowledge of the studied population towards PLWHA. According to publications
found the knowledge and attitudes have improved because the perception is more
favourable.
PMID- 27499565
TI - Optimal Convergence Rates Results for Linear Inverse Problems in Hilbert Spaces.
AB - In this article, we prove optimal convergence rates results for regularization
methods for solving linear ill-posed operator equations in Hilbert spaces. The
results generalizes existing convergence rates results on optimality to general
source conditions, such as logarithmic source conditions. Moreover, we also
provide optimality results under variational source conditions and show the
connection to approximative source conditions.
PMID- 27499564
TI - Asymptotically Normal and Efficient Estimation of Covariate-Adjusted Gaussian
Graphical Model.
AB - A tuning-free procedure is proposed to estimate the covariate-adjusted Gaussian
graphical model. For each finite subgraph, this estimator is asymptotically
normal and efficient. As a consequence, a confidence interval can be obtained for
each edge. The procedure enjoys easy implementation and efficient computation
through parallel estimation on subgraphs or edges. We further apply the
asymptotic normality result to perform support recovery through edge-wise
adaptive thresholding. This support recovery procedure is called ANTAC, standing
for Asymptotically Normal estimation with Thresholding after Adjusting
Covariates. ANTAC outperforms other methodologies in the literature in a range of
simulation studies. We apply ANTAC to identify gene-gene interactions using an
eQTL dataset. Our result achieves better interpretability and accuracy in
comparison with CAMPE.
PMID- 27499566
TI - Central Limit Theorems under additive deformations.
AB - Additive deformations of statistical systems arise in various areas of physics.
Classical central limit theory is then no longer applicable, even when standard
independence assumptions are preserved. This paper investigates ways in which
deformed algebraic operations lead to distinctive central limit theory. We
establish some general central limit results that are applicable to a range of
examples arising in nonextensive statistical mechanics, including the addition of
momenta and velocities via Kaniadakis addition, and Tsallis addition. We also
investigate extensions to random additive deformations, and find evidence (based
on simulation studies) for a universal limit specific to each statistical system.
PMID- 27499567
TI - Using the mouse grimace scale and behaviour to assess pain in CBA mice following
vasectomy.
AB - Mice used in biomedical research should have pain reduced to an absolute minimum
through refinement of procedures or by the provision of appropriate analgesia.
Vasectomy is a common and potentially painful surgical procedure carried out on
male mice to facilitate the production of genetically modified mice. The aim of
our study was to determine if 0.05 mg/kg buprenorphine would ameliorate pain
associated changes following abdominal vasectomy and to determine if the mouse
grimace scale is an appropriate tool for the assessment of pain in this model.
Eight male CBA mice underwent abdominal vasectomy as part of a genetically
modified mouse-breeding programme. Here we assessed pain using a previously
validated behaviour-based method and the mouse grimace scale. All mice received
buprenorphine (0.05 mg/kg s.c.) pre-surgery. Behaviour and grimace scores were
compared between baseline (pre-surgery), 30 min, 5 h, 24 h and 25 h post surgery.
Following 24 h post-op, all mice were administered 5 mg/kg meloxicam (s.c.) as
additional analgesia. Significant increases in specific pain behaviours and mouse
grimace scale score were found 30 min post surgery. At 5 h post surgery, scores
were returning to baseline levels. Frequency of rearing was significantly
decreased at both 30 min and 5 h post surgery compared to baseline, demonstrating
a longer lasting change in normal exploratory behaviour. Buprenorphine (0.05
mg/kg) was ineffective at ameliorating these pain-associated changes in CBA mice
and should be considered inadequate at this dose. By 24 h post surgery, pain
associated behaviours, grimace scale and rearing had all returned to baseline
levels. There was no change in pain behaviours or MGS following administration of
meloxicam indicating that an additional dose of meloxicam does not appear to
offer benefit at this point. Using the mouse grimace scale to assess pain in
mice, appeared to be effective in the immediate post vasectomy period in CBA mice
demonstrating the same duration of increased score as the pain associated
behaviours.
PMID- 27499568
TI - Balsscallichirus Sakai, 2011 (Decapoda: Axiidea: Callianassidae) in the fossil
record: systematics and palaeobiogeography.
AB - The fossil record of the ghost shrimp genus Balsscallichirus Sakai, 2011
(Crustacea: Decapoda: Callianassidae) is revised. Barnardcallichirus Sakai, 2011
and Tirmizicallichirus Sakai, 2011 are considered subjective synonyms of
Balsscallichirus. Based on the examination of extant species it is argued that
the morphology of the major cheliped merus, in combination with other hard part
morphology characters, is sufficient for assignment of the fossil material into
the genus. Main identifying characters are on merus which is keeled along its
midline and its lower half is tuberculated; its lower margin possesses broad
proximal meral hook continuing into a lobe distally; the entire lower margin is
subdivided into numerous irregularly spaced spines. Three species, Callianassa
sismondai A. Milne-Edwards, 1860, C. floriana Glaessner, 1928, and
Podocallichirus laepaensis Hyzny & Muniz, 2012, originally described from the
Miocene of Italy, Austria and Spain, respectively, are assigned to
Balsscallichirus herein. Neocallichirus wellsi Schweitzer, Feldmann & Gingerich,
2004 from the Upper Eocene of Pakistan is tentatively assigned to that genus as
well. Spatial and temporal distribution of the genus indicates that at least
since the Oligocene, and possibly even sooner (the Late Eocene), the genus has
been restricted to the Western Tethys Region. Later, it migrated also into West
Atlantic establishing present day communities.
PMID- 27499569
TI - Surface conductance of graphene from non-contact resonant cavity.
AB - A method is established to reliably determine surface conductance of single-layer
or multi-layer atomically thin nano-carbon graphene structures. The measurements
are made in an air filled standard R100 rectangular waveguide configuration at
one of the resonant frequency modes, typically at TE103 mode of 7.4543 GHz.
Surface conductance measurement involves monitoring a change in the quality
factor of the cavity as the specimen is progressively inserted into the cavity in
quantitative correlation with the specimen surface area. The specimen consists of
a nano-carbon-layer supported on a low loss dielectric substrate. The thickness
of the conducting nano-carbon layer does not need to be explicitly known, but it
is assumed that the lateral dimension is uniform over the specimen area. The non
contact surface conductance measurements are illustrated for a typical graphene
grown by chemical vapor deposition process, and for a high quality monolayer
epitaxial graphene grown on silicon carbide wafers for which we performed non
gated quantum Hall resistance measurements. The sequence of quantized transverse
Hall resistance at the Landau filling factors nu = +/-6 and +/-2, and the absence
of the Hall plateau at nu = 4 indicate that the epitaxially grown graphene is a
high quality mono-layer. The resonant microwave cavity measurement is sensitive
to the surface and bulk conductivity, and since no additional processing is
required, it preserves the integrity of the conductive graphene layer. It allows
characterization with high speed, precision and efficiency, compared to transport
measurements where sample contacts must be defined and applied in multiple
processing steps.
PMID- 27499570
TI - The Unilateralist's Curse and the Case for a Principle of Conformity.
AB - In some situations a number of agents each have the ability to undertake an
initiative that would have significant effects on the others. Suppose that each
of these agents is purely motivated by an altruistic concern for the common good.
We show that if each agent acts on her own personal judgment as to whether the
initiative should be undertaken, then the initiative will be undertaken more
often than is optimal. We suggest that this phenomenon, which we call the
unilateralist's curse, arises in many contexts, including some that are important
for public policy. To lift the curse, we propose a principle of conformity, which
would discourage unilateralist action. We consider three different models for how
this principle could be implemented, and respond to an objection that could be
raised against it.
PMID- 27499571
TI - Validation of Nonparametric Two-Sample Bootstrap in ROC Analysis on Large
Datasets.
AB - The nonparametric two-sample bootstrap is applied to computing uncertainties of
measures in ROC analysis on large datasets in areas such as biometrics, speaker
recognition, etc., when the analytical method cannot be used. Its validation was
studied by computing the SE of the area under ROC curve using the well
established analytical Mann-Whitney-statistic method and also using the
bootstrap. The analytical result is unique. The bootstrap results are expressed
as a probability distribution due to its stochastic nature. The comparisons were
carried out using relative errors and hypothesis testing. They match very well.
This validation provides a sound foundation for such computations.
PMID- 27499572
TI - Inhibition of neutrophil superoxide generation by shikonin is associated with
suppression of cellular Ca(2+) fluxes.
AB - Shikonin, an anti-inflammatory compound of "Shikon", inhibits the neutrophil
superoxide (O2 (*-)) generation by NADPH oxidase 2 (Nox2); however, the
mechanisms of how shikonin affects Nox2 activity remained unclear. We aimed to
elucidate the relationship between the inhibition of Nox2 activity and influences
on intracellular Ca(2+) concentration ([Ca(2+)]i) by shikonin. For this purpose,
we used a simultaneous monitoring system for detecting changes in [Ca(2+)]i (by
fluorescence) and O2 (*-) generation (by chemiluminescence) and evaluated the
effects of shikonin on neutrophil-like HL-60 cells stimulated with N-formyl-l
methionyl-l-leucyl-l-phenylalanine (fMLP). Since fMLP activates Nox2 by elevation
in [Ca(2+)]i via fluxes such as inositol 1,4,5-trisphosphate-induced Ca(2+)
release (IICR) and store-operated Ca(2+) entry (SOCE), we also evaluated the
effects of shikonin on IICR and SOCE. Shikonin dose-dependently inhibited the
fMLP-induced elevation in [Ca(2+)]i and O2 (*-) generation (IC50 values of 1.45
and 1.12 uM, respectively) in a synchronized manner. Analyses of specific Ca(2+)
fluxes showed that shikonin inhibits IICR and IICR-linked O2 (*-) generation
(IC50 values: 0.28 and 0.31 uM for [Ca(2+)]i and O2 (*-), respectively), as well
as SOCE and SOCE-linked O2 (*-) generation (IC50 values: 0.39 and 0.25 uM for
[Ca(2+)]i and O2 (*-), respectively). These results suggested that shikonin
inhibits the O2 (*-) generation by Nox2 in fMLP-stimulated neutrophils by
targeting Ca(2+) fluxes such as IICR and SOCE.
PMID- 27499573
TI - The effect of astaxanthin on vascular endothelial growth factor (VEGF) levels and
peroxidation reactions in the aqueous humor.
AB - We explored the effect of astaxanthin on vascular endothelial growth factor in
the aqueous humor, by measuring vascular endothelial growth factor levels and
oxidation-related parameters, including O2 (*-) scavenging activity, H2O2 level,
and total hydroperoxide level in the aqueous humor, obtained from 35 patients
before and after astaxanthin administration. We evaluated the relationship
between vascular endothelial growth factor and the oxidation-related parameters
as well as the patient's diabetic status, age, and sex. Vascular endothelial
growth factor levels did not change significantly but O2 (*-) scavenging activity
and total hydroperoxide level significantly (p<0.05) increased and decreased,
respectively. Both pre- and post- astaxanthin intake, vascular endothelial growth
factor and total hydroperoxide levels were positively correlated (Pearson: r =
0.42, p<0.05; r = 0.55, p<0.01, respectively). Analysis of vascular endothelial
growth factor levels and O2 (*-) scavenging activities gave a negative
correlation but only pre-astaxanthin intake (r = -0.37, p<0.05). Differences in
levels pre- and post-astaxanthin only showed association between vascular
endothelial growth factor and total hydroperoxide (r = 0.49, p<0.01) analyzed by
multiple linear regression. Using multivariate analysis, pre-astaxanthin vascular
endothelial growth factor level was associated with two factors of total
hydroperoxide and O2 (*-) scavenging activity (r = 0.49, p<0.05), and post
astaxanthin vascular endothelial growth factor level with two factors of total
hydroperoxide and sex (r = 0.60, p<0.01). Astaxanthin intake may have affected
vascular endothelial growth factor level through its antioxidant effects by
increasing O2 (*-) scavenging activity and suppressing peroxide production.
PMID- 27499574
TI - Lipid peroxides as endogenous oxidants forming 8-oxo-guanosine and lipid-soluble
antioxidants as suppressing agents.
AB - The oxidation of guanosine to 8-oxo-2'-deoxyguanosine (8-oxo-dG) in DNA is
closely associated with induction of various diseases, but the endogenous oxidant
species involved remains unclear. Hydrogen peroxides (H2O2) have been considered
to be the oxidant, while lipid peroxides are another possible oxidant because
generated easily in bio-membranes surrounding DNA. The oxidant potency was
compared between lipid peroxides and H2O2. Linoleic acid hydroperoxides (LOOH)
formed 8-oxo-dG at a higher level than H2O2 in guanosine or double-stranded DNA.
In the presence of a physiological concentration of Fe(2+) to produce hydroxyl
radicals, LOOH was also a stronger oxidant. In a lipid micelle, LOOH markedly
produced 8-oxo-dG at a concentration one-tenth of that of H2O2. Upon adding to
rat hepatic mitochondria, phosphatidylcholine hydroperoxides produced 8-oxo-dG
abundantly. Employing HepG2 cells after pretreated with glutathione peroxidase
inhibitor, LOOH formed 8-oxo-dG more abundantly than H2O2. Then, antioxidants to
suppress the 8-oxo-dG formation were examined, when the nuclei of pre-incubated
HepG2 with antioxidants were exposed to LOOH. Water-soluble ascorbic acid,
trolox, and N-acetyl cysteine showed no or weak antioxidant potency, while lipid
soluble 2,6-dipalmitoyl ascorbic acid, alpha-tocopherol, and lipid-soluble
phytochemicals exhibited stronger potency. The present study shows preferential
formation of 8-oxo-dG upon LOOH and the inhibition by lipid-soluble antioxidants.
PMID- 27499575
TI - F-fucoidan from Saccharina japonica is a novel inducer of galectin-9 and exhibits
anti-allergic activity.
AB - Fucoidan is a sulfated polysaccharide from brown sea algae. In the present study,
it was demonstrated that oral administration of F-fucoidan from Saccharina
japonica possessed anti-allergic effects using the passive cutaneous anaphylaxis
reaction, but not by intraperitoneal administration. The inhibitory mechanism was
dependent on galectin-9, which belongs to a soluble lectin family that recognizes
beta-galactoside and prevents IgE binding to mast cells. The anti-allergy
properties of F-fucoidan were cancelled by an intravenous dose of anti-galectin-9
antibody or lactose, which bind competitively with galectin-9 before the passive
cutaneous anaphylaxis reaction. F-fucoidan increased the expression level of
galectin-9 mRNA in intestinal epithelial cells and serum galectin-9 levels. Oral
treatment with F-fucoidan suppressed allergic symptoms through the induction of
galectin-9. This is the first report that F-fucoidan can induce the secretion of
galectin-9.
PMID- 27499576
TI - Cheonggukjang, a soybean paste fermented with B. licheniformis-67 prevents weight
gain and improves glycemic control in high fat diet induced obese mice.
AB - In this study, we investigated the anti-obesity effects of soybean paste
Cheonggukjang, fermented with poly gamma glutamic acid producing Bacillus
licheniformis-67 in diet induced obese C57BL/6J mice. Forty male C57BL/6J mice
aged 4 weeks were divided into four dietary groups; normal diet control, high fat
diet control, high fat diet containing 30% of unfermented soybean and high fat
diet containing 30% Cheonggukjang fermented with Bacillus licheniformis-67. After
13 weeks of dietary intervention the mice were sacrificed; serum and tissue
samples were examined. Serum and hepatic lipid profile, blood glucose, insulin,
leptin level were lower (<0.05) along with the body weight and epididymal fat pad
weight in the 30% Cheonggukjang supplemented group compared with the high fat
diet control group. The expression level of lipid anabolic gene was significantly
decreased; whereas the expression level of lipid catabolic genes were
significantly increased in the 30% Cheonggukjang supplemented group compared to
the high fat diet control group. Collectively, these results suggested that
intake of Cheonggukjang fermented with Bacillus licheniformis-67 significantly
prevents obesity related parameters.
PMID- 27499578
TI - Changes in salivary flow rate following Chlorella-derived multicomponent
supplementation.
AB - Decreases in saliva secretion compromise food mastication and swallowing, reduce
mucosal immune function, and increase the risk for oral diseases like dental
caries. Chlorella is a green alga that contains a variety of nutrients including
amino acids, vitamins, and minerals. In our previous study, Chlorella-derived
multicomponent supplementation did not affect salivary flow rates in healthy
young individuals, but Chlorella-derived supplementation attenuated a decrease in
saliva secretion that was observed during a kendo training camp. Hence, we
hypothesized that Chlorella-derived supplementation increases saliva secretion in
individuals with lower rates of saliva flow. Sixty-four subjects took Chlorella
derived tablets for four weeks. Before and after supplementation, saliva samples
were collected by chewing cotton. In the complete study group, there was no
difference in saliva production before and after supplementation (1.91 +/- 0.11
ml/min before vs 2.01 +/- 0.12 ml/min after). Analysis of subgroups based on
saliva production before supplementation found an increase in saliva secretion in
the lower saliva flow group (1.18 +/- 0.06 vs 1.38 +/- 0.08 ml/min), but no
change in the higher saliva flow group (2.63 +/- 0.11 vs 2.64 +/- 0.15 ml/min).
These results suggest that Chlorella-derived multicomponent supplementation
increases saliva production in individuals with lower levels of saliva secretion.
PMID- 27499577
TI - Pre-germinated brown rice prevented high fat diet induced hyperlipidemia through
ameliorating lipid synthesis and metabolism in C57BL/6J mice.
AB - Pre-germinated brown rice (PGBR) can ameliorate hyperlipidemia, but the action
mechanism is not clear. We focus the mechanisms of PGBR prevented hyperlipidemia.
Six-week-old mice were divided into: standard-regular diet (SRD), high-fat diet
(HFD) and HFD with PGBR (HFD + PGBR) groups for 16 weeks. The HFD group has
higher concentrations of TG, TC, HDL and Non-HDL in the blood, and a higher
atherosclerosis index (AI). The TG levels in the liver, and TG, bile acid levels
in the feces were enhanced; and the total adipocytokines level in adipose tissue
was reduced. The HFD group had higher protein expressions of SREBP-1, SCD-1, FAS,
LDLR, and CYP7alpha1 in the liver. Moreover, the greater expressions of SREBP-1,
SCD-1, FAS and the less expressions of PPAR-alpha and adiponectin were in adipose
tissue. In the HFD + PGBR group, the PGBR regulated the levels of TG, TC, HDL,
Non-HDL, AI and adipocytokines. PGBR increased more cholesterol and bile acid
exhaust in feces. The SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7alpha1 and PPAR-alpha
proteins in the liver; and the SREBP-1, SCD-1, FAS, PPAR-alpha and adiponectin
proteins in adipose tissue were reversed by PGBR. Taken together, PGBR can
improve lipid synthesis and metabolism, and we suggest PGBR is a recommendable
food for controlling hyperlipidemia.
PMID- 27499579
TI - Infectious disease during hospitalization is the major causative factor for
prolonged hospitalization: multivariate analysis of diagnosis procedure
combination (DPC) data of 20,876 cases in Japan.
AB - This study aimed to evaluate causative factors for prolonged hospitalization
based on hospitalization status, type of hospital ward, and comorbidities,
specifically diabetes mellitus and infectious diseases, in 20,876 patients
hospitalized in Saga University Hospital from April 1, 2012, to February 28,
2015. Prolonged hospitalization was defined as hospital days exceeding period 3
in the diagnosis procedure combination system. Among all factors, causative
(risk) factors for prolonged hospitalization were evaluated by multiple logistic
regression analysis. Multivariate analysis indicated causative factors for
prolonged hospitalization were aging, comorbid diabetes mellitus, time spent in
the intensive care unit, and infectious diseases contracted during
hospitalization. The risk factors for contracting infectious diseases during
hospitalization were aging, male sex, comorbid diabetes mellitus, and increased
number of days spent in period 3 in the diagnosis procedure combination code.
These data indicated that critical factors for discharge from hospital within an
appropriate time frame were prevention of infectious diseases during
hospitalization, and a fast and effective therapeutic approach to patients in the
intensive care unit.
PMID- 27499580
TI - The expression of IGF-1R in Helicobacter pylori-infected intestinal metaplasia
and gastric cancer.
AB - Overexpression of IGF-1R has been demonstrated in gastrointestinal cancers, and
its expression is reported as the result of the loss of tumor suppressors. IL-16
is involved in the pathophysiological process of chronic inflammatory diseases.
The aim of this study is to determine the changes in the expression of IGF-1R in
intestinal metaplasia (IM) and gastric cancer (GC) as well as the effect of
Helicobacter pylori (H. pylori) and IL-16 on cell proliferation and IGF-1R
expression in gastric cells. AGS cells were incubated with combinations of IL-16
and H. pylori. Gastric cell proliferation was studied by BrdU uptake. In H.
pylori infected mucosa, IGF-1R was significantly higher in IM than chronic
gastritis (CG), and also higher in GC than CG and IM. H. pylori significantly
decreased BrdU uptake. IL-16 increased BrdU uptake and IGF-1R on AGS cells which
had been decreased by H. pylori. Co-incubation with IL-16 increased the
expression of IGF-1R mRNA in H. pylori infected cells. We conclude that the
expression of IGF-1R in H. pylori infected gastric mucosa may indicate an early
stage of carcinogenesis. The IL-16 secretion by H. pylori can be a trigger for
the expression of IGF-1R, and it may also be a factor for gastric carcinogenesis.
PMID- 27499581
TI - Effect of vitamin A and Zn supplementation on indices of vitamin A status,
haemoglobin level and defecation of children with persistent diarrhea.
AB - To investigate the effect of vitamin A and Zn supplementation on vitamin A
status, haemoglobin level and defecation of children with persistent diarrhea, a
total of 160 paediatric patients were randomly assigned to one of four
intervention groups: daily supplementation of 1,500 IU VA for 14 days; daily Zn
supplementation for 14 days; daily supplementation with both VA and Zn for 14
days; no supplementation. One hundred twenty-seven children with persistent
diarrhea finished intervention (33 were lost to follow-up). Among the 127
children, 41 (32.28%) had anaemia, 104 (81.89%) had a VA deficiency and 38
(29.92%) had an iron insufficiency. Supplementation with VA or VA + Zn enhanced
the serum VA levels and ameliorated anaemia. Supplementation with Zn and VA + Zn
for 5 days significantly improved defecation, where the VA + Zn treatment
resulted in superior outcomes. After 14 days of intervention, the total
effectiveness rates were 93.94%, 96.77% and 96.67% in the three groups,
significantly greater than that of the non-supplementation group (72.73%). These
results indicate that single VA or concurrent VA + Zn supplementation can improve
vitamin A status, haemoglobin level and defecation. However, concurrent VA + Zn
supplementation is the optimal option and can shorten the duration of persistent
diarrhea and markedly improve nutritional status. (www.clinicaltrials.gov
registration number: ChiCTR-IOR-14005498).
PMID- 27499582
TI - Comparison of the gut microbial community between obese and lean peoples using
16S gene sequencing in a Japanese population.
AB - Altered gut microbial ecology contributes to the development of metabolic
diseases including obesity. In this study, we performed 16S rRNA sequence
analysis of the gut microbiota profiles of obese and lean Japanese populations.
The V3-V4 hypervariable regions of 16S rRNA of fecal samples from 10 obese and 10
lean volunteers were sequenced using the Illumina MiSeq(TM)II system. The average
body mass index of the obese and lean group were 38.1 and 16.6 kg/m(2),
respectively (p<0.01). The Shannon diversity index was significantly higher in
the lean group than in the obese group (p<0.01). The phyla Firmicutes and
Fusobacteria were significantly more abundant in obese people than in lean
people. The abundance of the phylum Bacteroidetes and the
Bacteroidetes/Firmicutes ratio were not different between the obese and lean
groups. The genera Alistipes, Anaerococcus, Corpococcus, Fusobacterium and
Parvimonas increased significantly in obese people, and the genera Bacteroides,
Desulfovibrio, Faecalibacterium, Lachnoanaerobaculum and Olsenella increased
significantly in lean people. Bacteria species possessing anti-inflammatory
properties, such as Faecalibacterium prausnitzii, increased significantly in lean
people, but bacteria species possessing pro-inflammatory properties increased in
obese people. Obesity-associated gut microbiota in the Japanese population was
different from that in Western people.
PMID- 27499583
TI - Persistent reflux symptoms cause anxiety, depression, and mental health and sleep
disorders in gastroesophageal reflux disease patients.
AB - Some patients with gastroesophageal reflux disease experience persistent reflux
symptoms despite proton pump inhibitor therapy. These symptoms reduce their
health-related quality of life. Our aims were to evaluate the relationship
between proton pump inhibitor efficacy and health-related quality of life and to
evaluate predictive factors affecting treatment response in Japanese patients.
Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal
reflux disease patients undergoing proton pump inhibitor therapy were evaluated
and classified as responders or partial-responders. Their health-related quality
of life was then evaluated using the 8-item Short Form Health Survey, the
Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale
questionnaires. Sixty-nine patients (47.6%) were partial responders. These
patients had significantly lower scores than responders in 5/8 subscales and in
the mental health component summary of the 8-item Short Form Health Survey.
Partial responders had significantly higher Pittsburgh Sleep Quality Index and
Hospital Anxiety and Depression Scale scores, including anxiety and depression
scores, than those of responders. Non-erosive reflux disease and double proton
pump inhibitor doses were predictive factors of partial responders. Persistent
reflux symptoms, despite proton pump inhibitor therapy, caused mental health
disorders, sleep disorders, and psychological distress in Japanese
gastroesophageal reflux disease patients.
PMID- 27499584
TI - Erratum.
AB - [This corrects the article DOI: 10.3164/jcbn.15-90.].
PMID- 27499586
TI - An objectively-analyzed method for measuring the useful penetration of x-ray
imaging systems.
AB - The ability to detect wires is an important capability of the cabinet x-ray
imaging systems that are used in aviation security as well as the portable x-ray
systems that are used by domestic law enforcement and military bomb squads. A
number of national and international standards describe methods for testing this
capability using the so called useful penetration test metric, where wires are
imaged behind different thicknesses of blocking material. Presently, these tests
are scored based on human judgments of wire visibility, which are inherently
subjective. We propose a new method in which the useful penetration capabilities
of an x-ray system are objectively evaluated by an image processing algorithm
operating on digital images of a standard test object. The algorithm
advantageously applies the Radon transform for curve parameter detection that
reduces the problem of wire detection from two dimensions to one. The sensitivity
of the wire detection method is adjustable and we demonstrate how the threshold
parameter can be set to give agreement with human-judged results. The method was
developed to be used in technical performance standards and is currently under
ballot for inclusion in a US national aviation security standard.
PMID- 27499587
TI - Error Propagation Dynamics of PIV-based Pressure Field Calculations: How well
does the pressure Poisson solver perform inherently?
AB - Obtaining pressure field data from particle image velocimetry (PIV) is an
attractive technique in fluid dynamics due to its noninvasive nature. The
application of this technique generally involves integrating the pressure
gradient or solving the pressure Poisson equation using a velocity field measured
with PIV. However, very little research has been done to investigate the dynamics
of error propagation from PIV-based velocity measurements to the pressure field
calculation. Rather than measure the error through experiment, we investigate the
dynamics of the error propagation by examining the Poisson equation directly. We
analytically quantify the error bound in the pressure field, and are able to
illustrate the mathematical roots of why and how the Poisson equation based
pressure calculation propagates error from the PIV data. The results show that
the error depends on the shape and type of boundary conditions, the dimensions of
the flow domain, and the flow type.
PMID- 27499585
TI - Fifteen years of cold matter on the atom chip: promise, realizations, and
prospects.
AB - Here we review the field of atom chips in the context of Bose-Einstein
Condensates (BEC) as well as cold matter in general. Twenty years after the first
realization of the BEC and 15 years after the realization of the atom chip, the
latter has been found to enable extraordinary feats: from producing BECs at a
rate of several per second, through the realization of matter-wave
interferometry, and all the way to novel probing of surfaces and new forces. In
addition, technological applications are also being intensively pursued. This
review will describe these developments and more, including new ideas which have
not yet been realized.
PMID- 27499588
TI - Greetings from the new chief editors.
PMID- 27499589
TI - Calcium fortification or supplementation in postmenopausal females: Recent
controversy.
PMID- 27499590
TI - Coronary artery disease and its association with Vitamin D deficiency.
AB - Coronary artery disease (CAD) has become the latest scourge of humankind and
referred to in this article as CAD, is the end result of the accumulation of
atheromatous plaques within the walls of coronary arteries that supply the
myocardium, a process also known as atherosclerosis and manifests mostly in the
form of chronic stable angina or acute coronary syndrome. Vitamin D has attracted
considerable interest recently due to its role in a number of extraskeletal
disease processes including multiple sclerosis, malignancies, diabetes mellitus,
and CAD. It is also known as sunshine vitamin due to its production in the body
following exposure to ultraviolet rays, and it is a unique vitamin as it acts
like a hormone with its receptor present in a wide range of tissues including
endothelium, which is the important mediator of atherosclerosis and subsequent
CAD. A large number of studies conducted in the past have provided the basic
scientific framework and this article attempts to explore the role of Vitamin D
deficiency in the pathogenesis of CAD and stresses the need for further research
to fill up gap in our knowledge.
PMID- 27499591
TI - Role of therapeutic fasting in women's health: An overview.
AB - Fasting is a therapeutic tool practiced since millennia by different cultures and
medical systems heterogeneously. PubMed and Google Scholar search engines were
searched using the keywords "fasting," "intermittent fasting," "calorie
restriction," "women's health," "women's disorders," "fasting and aging," and
"fasting and health." All the animal and human studies which address women's
health and disorders were included in the review. Fasting has shown to improve
the reproductive and mental health. It also prevents as well as ameliorates
cancers and musculoskeletal disorders which are common in middle-aged and elderly
women. The present studies available have limitations such as majority of the
studies are preclinical studies and human studies are with lesser sample size.
Future studies should address this gap by designing medically supervised fasting
techniques to extract better evidence. Nevertheless, fasting can be prescribed as
a safe medical intervention as well as a lifestyle regimen which can improve
women's health in many folds.
PMID- 27499593
TI - Type II endometrial cancers: A case series.
AB - INTRODUCTION: Endometrial carcinoma ranks 3(rd) in India among gynecological
malignancies. Endometrial cancer (EC) can be classified into two distinct groups
type I and type II, based on histology, which differs in molecular, clinical and
histopathological profiles. Type II is nonestrogen dependent, nonendometrioid,
more aggressive and carries poor prognosis. Although type II cancers contribute
only about 10% of EC incidence, they present at advanced age and cause
approximately 50% recurrence and deaths with a low 5-year, overall survival rate.
Type II EC are also characterized by genetic alterations in p53, human epidermal
growth factor-2/neu, p16 and E-cadherin. MATERIALS AND METHODS: Endometrial
carcinomas diagnosed from endometrial biopsies and hysterectomy specimens
received in the Department of Pathology, Kasturba Medical College, Mangalore,
from January 2007 to June 2012 were included in the study. Clinicopathological
analysis of the 84 cases of EC was done with emphasis on morphology. p53
immunostaining was performed in two cases of serous carcinoma. RESULTS: Out of a
total of 84 cases of EC, ten cases were of type II (11.9%). Out of which, eight
were serous carcinoma (9.5%) and two clear cell (2.4%). p53 immunostain was
strongly positive in the serous papillary carcinomas. The age of the patients
ranged from 45 to 75 years. Myometrial invasion was more than half. Treatment was
hysterectomy followed by aggressive chemotherapy. CONCLUSION: Of the type II EC,
serous carcinoma is the most common type. Clinical presentation and prognosis
differs in comparison to type I EC, thus the recognition of this type of EC is
pivotal.
PMID- 27499592
TI - Postoperative pain relief following hysterectomy: A randomized controlled trial.
AB - BACKGROUND: Women experience moderate to severe postoperative pain following
total abdominal hysterectomy (TAH). The transversus abdominis plane (TAP) block
is a new modality for providing postoperative pain relief in these patients.
MATERIALS AND METHODS: The present study was a single center, prospective
randomized trial. After the Institutional Ethics Committee approval and informed
consent, patients were randomized to either epidural group: Epidural block
placement + general anesthesia (GA) or TAP group: Single shot TAP block + GA.
Patients in both the groups received standard general anesthetic technique and
intravenous tramadol patient-controlled analgesia in the postoperative period.
Patients were monitored for tramadol consumption, visual analog scale (VAS) both
at rest and on coughing, hemodynamics, and side effects at 0, 2, 4, 6, 8, 12, and
24 h postoperatively. RESULTS: The total consumption of tramadol in 24 h was
greater in TAP group as compared to epidural group (68.8 [25.5] vs. 5.3 [11.6]
mg, P < 0.001). The VAS scores at rest and on coughing were higher in TAP group
as compared to the epidural group at 6, 8, 12, and 24 h postoperatively (P <
0.05). None of the patients in either group had any adverse effects. CONCLUSION:
Epidural analgesia provided greater tramadol-sparing effect with superior
analgesia postoperatively as compared to TAP block in patients up to 24 h
following TAH.
PMID- 27499594
TI - Abnormal uterine bleeding in perimenopausal women: Correlation with sonographic
findings and histopathological examination of hysterectomy specimens.
AB - BACKGROUND: Abnormal uterine bleeding (AUB) is a frequently encountered
gynecologic complaint in perimenopausal woman and also the most common cause of
hysterectomy in this age group. OBJECTIVE: Evaluation of various clinical
presentations of perimenopausal AUB and it is ultrasonographic and
histopathological correlation of hysterectomy specimens. MATERIALS AND METHODS:
This study was carried out in the Department of Obstetrics and Gynaecology among
perimenopausal women who underwent hysterectomy for AUB. The clinical
presentations, ultrasonographic findings, and histopathological reports of
hysterectomy specimen were correlated. RESULTS: Among 103 number of
hysterectomized cases for AUB, most of the patients were between 40 and 45 years
of age (67.97%) and menorrhagia was the dominant clinical presentation. The
majority (45.63%) of cases were diagnosed as fibroid uterus by ultrasonography
with 89.13% sensitivity and 89.47% specificity. Histopathological reports of
myometrium showed 44.66% fibromyoma, followed by 34.95% of the normal myometrium.
Histopathology of endometrium revealed hyperplasia in the most cases (56.31%)
where simple typical type was the predominant. CONCLUSION: Uterine fibroid was
the leading cause of AUB and radiological, pathological evaluation correlated
well to diagnose fibroid.
PMID- 27499595
TI - Clinical, radiological, and histopathological analysis of paraovarian cysts.
AB - INTRODUCTION: Paraovarian cyst arise from either mesothelium or from
paramesonephric remnant. These present as either adneal mass or as an incidental
finding. Diagnosis is usually established on ultrasound and it is important to
differentiate these from ovarian cyst. MATERIAL AND METHODS: The present study is
a retrospective analysis of 32 women with a confirmed diagnosis of paraovarian
cyst after surgery. The clinical profile, symptoms and radiological findings of
these patients were noted from the hospital records. A correlation was made with
the surgical findings and the final histopathological diagnosis. RESULTS: Only 2
patients were postmenopausal and one case was diagnosed during pregnancy.
Ultrasound accurately diagnosed paraovarian cyst in 87.5% patients. 78%
paraovarian cysts were found to be simple and none had any malignant change. We
reported a higher incidence of cystic adenomatoid tumor in these paraovarian
cysts. CONCLUSION: In our study, most paraovarian cysts occur in reproductive age
group and present as an adnexal mass. Ultrasound is the diagnostic modality and a
paraovarian cyst needs to be differentiated from ovarian cyst. Most of them were
simple cysts on histopathology.
PMID- 27499596
TI - Burgeoning menopausal symptoms: An urgent public health concern.
AB - INTRODUCTION: Demographic and epidemiological transitions have increased the life
expectancy of people in India. This has resulted in higher burden of morbidities
related to aging. The National Health programmes have focused mainly on the
health of women in reproductive age groups and neglected their health thereafter.
Thus, there is a need to explore the bio-social correlates of menopausal symptoms
among women, which can influence their quality of life. SUBJECTS AND METHODS:
This cross-sectional community-based study was conducted in the urban slum of
Mysore for 3 months. A total of 100 postmenopausal women in the age group of 40
65 years residing in the field practice area of Urban Health Training Centre were
selected by simple random sampling method from the database of households.
Details regarding socio-demographic characteristics, postmenopausal symptoms, and
factors associated with them were collected in a pretested structured pro forma
by interview technique. RESULTS: Among 100 women included in the present study,
mean age at menarche and menopause was 13.45 +/- 1.72 and 46.7 +/- 5.2 years,
respectively. The most common postmenopausal symptom was joint pain (92%)
followed by physical and mental exhaustion (84%), depression (76%), irritability
(73%), hot flushes, and night sweats (65%). There was a significant positive
correlation between age of the women, duration of life after menopause, and
postmenopausal symptoms. CONCLUSION: There is a high burden of postmenopausal
symptoms which have shown an increasing trend with advancement of age. This calls
for establishment of specific health interventions for postmenopausal women in
the health-care settings.
PMID- 27499597
TI - Xanthogranulomatous endometritis presenting as pyometra and mimicking carcinoma
on imaging.
AB - Xanthogranulomatous endometritis (XGE) is an uncommon but well-established
histopathological entity seen affecting the kidney and gallbladder. Involvement
of the endometrium is very rare, with only a few case reports in world literature
till date. Histologically, it is characterized by the replacement of the
endometrium by sheets of foamy histiocytes, plasma cells, lymphocytes, giant
cells, and siderophages. We present a case of a 74-year-old female who presented
with foul-smelling discharge and postmenopausal bleeding of a short duration.
Clinical examination and imaging studies revealed a pyometra, cervical stenosis.
A suspicion of carcinoma was raised. Since XGE may mimic an endometrial carcinoma
clinically and pathologically, knowledge of this unusual and rare inflammatory
pathology is important for both the gynecologists and the pathologists.
PMID- 27499598
TI - Complete molar pregnancy in postmenopausal women.
AB - Gestational trophoblastic disease (GTD) is an abnormal proliferation of
trophoblastic tissue during pregnancy. It is a disease of reproductive age, and a
few cases have also been seen in women with advanced age, although it is
extremely rare in postmenopausal women. Here, we describe an uncommon case of
complete hydatidiform mole (CHM) in a postmenopausal woman, who has presented to
us with complaints of bleeding per vagina, vomiting with 22 weeks size gravid
uterus. Ultrasound finding along with raised serum beta-human chorionic
gonadotropin (beta-HCG) 400,000 mIU/ml suggested the diagnosis of CHM. In view of
postmenopausal status and future risk of postmolar gestational trophoblastic
neoplasia, we performed a total abdominal hysterectomy. Uterus was 20 cm * 15 cm
* 15 cm filled with cystic, grapes such as vesicles. Microscopic examination
demonstrated generalized trophoblastic proliferation with hydropic degenerated
villi suggested of benign CHM. Follow-up showed steady fall in serum beta-HCG
level and no evidence of any residual disease. A suspicion of GTD should be kept
in mind while evaluating a patient with peri- or post-menopausal bleeding so that
it will prevent a delay in diagnosis and treatment.
PMID- 27499599
TI - A rare case of renal metastasis from squamous cell carcinoma of the cervix.
AB - Cervical cancer is the most frequent type of cancer in women in many developing
countries. Squamous cell carcinoma of the cervix spreads principally by
lymphatics and less commonly through blood vessels. The most frequent sites for
those who develop distant metastasis include lungs (21%), lumbar and thoracic
spine (16%), and para-aortic lymph nodes (7%). Metastasis to the kidney is
extremely rare with <10 previously reported cases. We report a case of renal
metastasis from squamous cell carcinoma of the cervix detected in end-stage
kidney due to hydronephrosis.
PMID- 27499600
TI - A transvaginal removal and repair of vesicovaginal fistula due to mesh erosion.
AB - Vesicovaginal fistula (VVF) is a devastating social problem. It can either result
from obstetric trauma or following gynecological surgeries, malignancy, or
radiation. We present a case of a 70-year-old woman who had a VVF following mesh
augmentation surgery for anterior compartment prolapse. She required a
transvaginal removal of the eroded mesh followed by a transvaginal repair of VVF
using a Martius flap, 6 weeks later. Transvaginal removal of mesh is technically
feasible and a good approach. Timing and route of surgery should be
individualized.
PMID- 27499601
TI - Temporary agency work, migration and the crisis in Greece: labour market
segmentation intensified.
AB - This article focuses on the under-researched temporary agency employment in
Greece. It shows that the development of the temporary employment agency sector
has gone hand in hand with the flow of undocumented and exploitable migrant
labour in Greece over the past 25 years, reflecting the segmentation of the Greek
labour market along ethnic lines. Using empirical research evidence on the
operation of temporary employment agencies in the Greek hospitality and health
care sectors, the article highlights the precarious or even illicit nature of
agency employment in a context in which labour outsourcing and flexible
employment are promoted by policy-makers. Last but not least, it suggests that
the segmented landscape of the Greek labour market has become more complex during
the economic crisis, with more and more Greeks drawn to agency-mediated
precarious employment.
PMID- 27499602
TI - Implications of Teacher Life-Work Histories for Conceptualisations of 'Care':
Narratives from Rural Zimbabwe.
AB - Schools are increasingly seen as key sites for support to HIV-affected and other
vulnerable children, and teachers are assigned the critical role of identifying
and providing psychosocial support. Drawing on the life-work history narratives
of 12 teachers in Zimbabwe, this paper explores the psychosocial processes
underpinning teachers' conceptualisations of these caring roles. The influence of
prolonged adversity, formative relationships, and broader patterns of social and
institutional change in teacher identity formation processes speak to the complex
and embodied nature of understandings of 'care'. In such extreme settings
teachers prioritise the material and disciplinary aspects of 'care' that they see
as essential for supporting children to overcome hardship. This focus not only
means that emotional support as envisaged in international policy is commonly
overlooked, but also exposes a wider ideological clash about childrearing. This
tension together with an overall ambivalence surrounding teacher identities puts
further strain on teacher-student relationships. We propose the current trainings
on providing emotional support are insufficient and that more active focus needs
to be directed at support to teachers in relation with their students. (c) 2015
The Authors. Journal of Community & Applied Social Psychology published by John
Wiley & Sons Ltd.
PMID- 27499603
TI - Identification of novel natural compound inhibitors for human complement
component 5a receptor by homology modeling and virtual screening.
AB - ABSTRACT: Neuropathic pain and inflammatory pain are two common types of
pathological pain in human health problems. To date, normal painkillers are only
partially effective in treating such pain, leading to a tremendous demand to
develop new chemical entities to combat pain and inflammation. A promising
pharmacological treatment is to control signal transduction via the inflammatory
mediator-coupled receptor protein C5aR by finding antagonists to inhibit C5aR
activation. Here, we report the first computational study on the identification
of non-peptide natural compound inhibitors for C5aR by homology modeling and
virtual screening. Our study revealed a novel natural compound inhibitor
Acteoside with better docking scores than all four existing non-peptidic natural
compounds. The MM-GBSA binding free energy calculations confirmed that Acteoside
has a decrease of ~39 kcal/mol in the free energy of binding compared to the
strongest binding reference compound. Main contributions to the higher affinity
of Acteoside to C5aR are the exceptionally strong lipophilic interaction,
enhanced electrostatics and hydrogen bond interactions. Detailed analysis on the
physiochemical properties of Acteoside suggests further directions in lead
optimization. Taken together, our study proposes that Acteoside is a potential
lead molecule targeting the C5aR allosteric site and provides helpful information
for further experimental studies. GRAPHICAL ABSTRACT:
PMID- 27499604
TI - Synthesis, antibacterial and antiproliferative potential of some new 1
pyridinecarbonyl-4-substituted thiosemicarbazide derivatives.
AB - In this study, the antibacterial, cytotoxic and antiproliferative activities of
novel thiosemicarbazide derivatives were assessed. Our results demonstrated that
some of the novel compounds possess good antibacterial properties against
Staphylococcus epidermidis, Streptococcus mutans and Streptococcussanguinis and
are only slightly cytotoxic; thus, they exhibit an excellent therapeutic index,
which is higher than that of ethacridine lactate. Moreover, our data showed that
compounds 2 and 4 have an antiproliferative activity against human breast
adenocarcinoma and human hepatocellular carcinoma cell lines. We expect that the
novel thiosemicarbazide derivatives can be used as agents for treatment of dental
caries and also for chemotherapy support.
PMID- 27499605
TI - Anisotropic fractional diffusion tensor imaging.
AB - Traditional diffusion tensor imaging (DTI) maps brain structure by fitting a
diffusion model to the magnitude of the electrical signal acquired in magnetic
resonance imaging (MRI). Fractional DTI employs anomalous diffusion models to
obtain a better fit to real MRI data, which can exhibit anomalous diffusion in
both time and space. In this paper, we describe the challenge of developing and
employing anisotropic fractional diffusion models for DTI. Since anisotropy is
clearly present in the three-dimensional MRI signal response, such models hold
great promise for improving brain imaging. We then propose some candidate models,
based on stochastic theory.
PMID- 27499606
TI - Emotion Regulation Therapy for Generalized Anxiety Disorder.
AB - Despite the success of cognitive behavioral therapies (CBT) for emotional
disorders, a sizable subgroup of patients with complex clinical presentations,
such as patients with generalized anxiety disorder, fails to evidence adequate
treatment response. Emotion Regulation Therapy (ERT) integrates facets of
traditional and contemporary CBTs, mindfulness, and emotion-focused interventions
within a framework that reflects basic and translational findings in affect
science. Specifically, ERT is a mechanism-targeted intervention focusing on
patterns of motivational dysfunction while cultivating emotion regulation skills.
Open and randomized controlled psychotherapy trials have demonstrated
considerable preliminary evidence for the utility of this approach as well as for
the underlying proposed mechanisms. This article provides an illustration of ERT
through the case of "William." In particular, this article includes a case
conceptualization of William from an ERT perspective while describing the flow
and progression of the ERT treatment approach.
PMID- 27499607
TI - Advances in Photocatalysis: A Microreview of Visible Light Mediated Ruthenium and
Iridium Catalyzed Organic Transformations.
AB - Photocatalytic organic transformations utilizing ruthenium and iridium complexes
have garnered significant attention due to the access they provide to new
synthetic spaces through new reaction mechanisms. A survey of the photophysical
data and the diversity of transformations that may be accomplished utilizing
commercially available photocatalysts is contained herein.
PMID- 27499610
TI - Comments on: Probability Enhanced Effective Dimension Reduction for Classifying
Sparse Functional Data.
PMID- 27499609
TI - Tissue factor induces VEGF expression via activation of the Wnt/beta-catenin
signaling pathway in ARPE-19 cells.
AB - PURPOSE: The purpose of the present study was to investigate the potential signal
mechanism of tissue factor (TF) in the regulation of the expression of vascular
endothelial growth factor (VEGF) in human retinal pigment epithelial (ARPE-19)
cells. METHODS: An in vitro RPE cell chemical hypoxia model was established by
adding cobalt chloride (CoCl2) in the culture medium. The irritative
concentration of CoCl2 was determined with a 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyl tetrazolium bromide (MTT) assay kit. VEGF production in ARPE-19 cells
was measured with enzyme-linked immunosorbent assay (ELISA) and western blotting.
The Wnt signaling pathway-associated molecules, including phospho-glycogen
synthase kinase 3beta (p-GSK3beta), GSK3beta, p-beta-catenin and beta-catenin,
were detected with western blotting. pEGFP-N3-hTF was constructed and verified
with digestion of the restriction enzyme and sequencing analysis. Human TF
overexpression and silencing plasmids were transfected into the ARPE-19 cells to
clarify the causal relationship between TF and VEGF expression. The Transwell
coculture system of ARPE-19 cells and RF/6A rhesus macaque choroid-retinal
endothelial cells was performed to evaluate cell invasion and tube formation
ability. RESULTS: Our anoxic model of ARPE-19 cells showed that TF expression was
upregulated in accordance with variations in hypoxia-inducible factor 1-alpha
(HIF-1alpha) and VEGF levels. Silencing and overexpression of TF decreased and
increased VEGF expression, respectively. The Wnt/beta-catenin signaling pathway
played an important role in this effect. Results from the ARPE-19 cell and RF/6A
cell coculture system showed that the enhancement of TF expression in the ARPE-19
cells led to significantly faster invasion and stronger tube-forming ability of
the RF/6A cells, while siRNA-mediated TF silencing caused the opposite effects.
Pharmacological disruption of Wnt signaling IWR-1-endo inhibited the effects
compared to the TF-overexpressing group, indicating the importance of the
Wnt/beta-catenin signaling pathway in the process of TF-induced VEGF expression
and angiogenesis. CONCLUSIONS: Involvement of the activation of the Wnt/beta
catenin signaling pathway is an important mediator for TF-induced VEGF production
during the process of angiogenesis. Thus, our findings may ascertain the
molecular regulation of TF in neovessel formation and show significant
therapeutic implications.
PMID- 27499611
TI - Axial length, refraction, and retinal vascularization 1 year after ranibizumab or
bevacizumab treatment for retinopathy of prematurity.
AB - PURPOSE: The purpose of this study was to report on the axial length, refraction,
and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for
threshold retinopathy of prematurity. METHODS: The authors conducted a
comparative, consecutive, original study. RESULTS: Twenty-five eyes of 13
patients with threshold retinopathy of prematurity received one intravitreal
ranibizumab treatment, and 15 eyes of eight patients received one intravitreal
bevacizumab treatment. In the ranibizumab group, the mean gestational age was
26.15+/-2.08 weeks, with a mean birth weight of 811.15+/-287.3 g. In the
bevacizumab group, the mean gestational age was 26.50+/-2.14 weeks, with a mean
birth weight of 938.38+/-200.4 g. The mean axial length was 20.34+/-0.97 mm and
the mean spherical equivalent was 0.46+/-1.36 D in the ranibizumab group, with
complete vascularization in 15 of 25 (60%) eyes. The mean axial length was
20.91+/-1.54 mm and the mean spherical equivalent was -0.60+/-3.86 D in the
bevacizumab group, with complete vascularization in seven of 15 (46.7%) eyes.
CONCLUSION: There were no significant differences in the axial length and
refraction between children with threshold retinopathy of prematurity who
received intravitreal bevacizumab compared to those who received ranibizumab
after 1 year of follow-up. It appeared that the ranibizumab treatment could
achieve more complete retinal vascularization than the bevacizumab treatment;
however, there was no statistical significance and long-term follow-up is needed.
PMID- 27499608
TI - The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic
acid cycle, oxidative phosphorylation, and ~P transferring kinases.
AB - PURPOSE: The homeostatic regulation of cellular ATP is achieved by the
coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the
major substrate for ATP synthesis through glycolysis and oxidative
phosphorylation (OXPHOS), whereas intermediary metabolism through the
tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates,
amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis.
Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate
(~P) transferring kinases. Our goals were twofold: 1) to characterize the gene
expression, protein expression, and activity of key synthesizing and regulating
enzymes of energy metabolism in the whole mouse retina, retinal compartments,
and/or cells and 2) to provide an integrative analysis of the results related to
function. METHODS: mRNA expression data of energy-related genes were extracted
from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from
adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal
microscopy, and enzymatic histochemistry. The immunoreactivity levels of well
characterized antibodies, for all major retinal cells and their compartments,
were obtained using our established semiquantitative confocal and imaging
techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH)
activity was determined histochemically. RESULTS: The Affymetrix data revealed
varied gene expression patterns of the ATP synthesizing and regulating enzymes
found in the muscle, liver, and brain. Confocal studies showed differential
cellular and compartmental distribution of isozymes involved in glucose,
glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity
of the antibodies and of the COX and LDH activity showed the high capacity of
photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with
pyruvate revealed that LDH-5 was localized in the photoreceptor inner segments.
The combined results indicate that glycolysis is regulated by the compartmental
expression of hexokinase 2, pyruvate kinase M1, and pyruvate kinase M2 in
photoreceptors, whereas the inner retinal neurons exhibit a lower capacity for
glycolysis and aerobic glycolysis. Expression of nucleoside diphosphate kinase,
mitochondria-associated adenylate kinase, and several mitochondria-associated
creatine kinase isozymes was highest in the outer retina, whereas expression of
cytosolic adenylate kinase and brain creatine kinase was higher in the cones,
horizontal cells, and amacrine cells indicating the diversity of ATP-buffering
strategies among retinal neurons. Based on the antibody intensities and the COX
and LDH activity, Muller glial cells (MGCs) had the lowest capacity for
glycolysis, aerobic glycolysis, and OXPHOS. However, they showed high expression
of glutamate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate
thiokinase, GABA transaminase, and ~P transferring kinases. This suggests that
MGCs utilize TCA cycle anaplerosis and cataplerosis to generate GTP and ~P
transferring kinases to produce ATP that supports MGC energy requirements.
CONCLUSIONS: Our comprehensive and integrated results reveal that the adult mouse
retina expresses numerous isoforms of ATP synthesizing, regulating, and buffering
genes; expresses differential cellular and compartmental levels of glycolytic,
OXPHOS, TCA cycle, and ~P transferring kinase proteins; and exhibits differential
layer-by-layer LDH and COX activity. New insights into cell-specific and
compartmental ATP and GTP production, as well as utilization and buffering
strategies and their relationship with known retinal and cellular functions, are
discussed. Developing therapeutic strategies for neuroprotection and treating
retinal deficits and degeneration in a cell-specific manner will require such
knowledge. This work provides a platform for future research directed at
identifying the molecular targets and proteins that regulate these processes.
PMID- 27499612
TI - Characterization of the serological biomarkers associated with Sjogren's syndrome
in patients with recalcitrant dry eye disease.
AB - PURPOSE: The purpose was to characterize the biomarkers associated with Sjogren's
syndrome (SS) identified in the serological samples of patients with recalcitrant
dry eye disease; additionally, the modalities utilized in the treatment of dry
eye disease were evaluated for subsets of patients with and without SS. PATIENTS
AND METHODS: Data for this retrospective, single-center, pilot study were based
on a chart review of 48 sequential patients with recalcitrant dry eye who were
evaluated for SS via serological analysis. Data presented include the presence of
the autoantibodies identified through the serological biomarker analysis and
identification of the concurrent dry eye treatment modalities. RESULTS: Eleven
out of 48 patients (23%) tested positive for biomarkers associated with SS.
Autoantibodies for salivary protein-1, parotid secretory protein 1, and carbonic
anhydrase VI, markers associated with the early development of SS, were detected
in 91% (ten out of eleven) of the patients who tested positive for SS, whereas
27% (three out of eleven) of patients tested positive for the traditional SS
markers, SS-A and/or SS-B. Common treatment modalities utilized in SS patients
included omega-3 supplements (82%), topical cyclosporine (74%), and artificial
tear solutions (64%), as compared to omega-3 supplements (80%), hot-mask therapy
(77%), and artificial tear solutions (77%), in SS-negative patients. CONCLUSION:
Evaluation for salivary protein-1, parotid secretory protein 1, and carbonic
anhydrase VI biomarkers allows for identification of a subset of patients with
biomarkers associated with SS that may not be identified through the traditional
assessments (SS-A/SS-B). Earlier recognition of SS biomarkers allows for a
confirmatory diagnosis and appropriate management of this systemic, progressive
condition.
PMID- 27499613
TI - Frequency and risk factors associated with dry eye in patients attending a
tertiary care ophthalmology center in Mexico City.
AB - PURPOSE: The purpose of this study was to ascertain the frequency and risk
factors of dry eye (DE) among patients attending a tertiary care ophthalmology
center in Mexico. METHODS: Approximately 338 consecutive new patients attending a
tertiary care ophthalmology center in Mexico City underwent an ocular surface
examination, which included tear film break-up time, fluorescein corneal
staining, Schirmer's test, and evaluation of meibum quality. Symptoms of DE were
evaluated by the Ocular Surface Disease Index and Dry Eye Questionnaire-5.
Information on demographics, exposures, past medical and ocular history, and
medications was also collected. RESULTS: The frequency of severe DE symptoms was
found to be 43% based on the Ocular Surface Disease Index and 30% based on Dry
Eye Questionnaire-5. Risk factors significantly associated with increased DE
symptoms included dry mouth and gastrointestinal ulcer medications. With regard
to signs, aqueous tear deficiency was a less-frequent finding (22%) in our
population than evaporative deficiency (94%). Risk factors associated with
aqueous tear deficiency were dry mouth and diuretic use. No risk factors were
associated with evaporative deficiency. Risk factors associated with meibomian
gland dysfunction included old age, male sex, arthritis, and use of an
antihypertensive. The only risk factor associated with corneal staining was dry
mouth. CONCLUSION: This is the first study to demonstrate the frequency of
symptomatic and clinical DE in a tertiary care ophthalmology center in Mexico.
The frequency of DE ranged from 30% using a symptomatic definition to 94% using
objective measures. Different risk factors were found for different aspects of
DE, suggesting differing underlying pathophysiologies behind different DE
subtypes.
PMID- 27499614
TI - The psychometric properties of Chinese version of SCI Exercise Self-Efficacy
Scale in patients with stroke.
AB - OBJECTIVE: To test the Chinese version of the SCI Exercise Self-Efficacy Scale (C
ESES) in stroke patients and evaluate its validity and reliability. BACKGROUND:
Physical inactivity is a well established and changeable risk factor for stroke,
and regular exercise of 3-7 days per week is essential for stroke survivors and
the general population. Though regular exercise is beneficial, it has been proved
that duration, frequency, and intensity of exercise are generally low in stroke
survivors. METHODS: The performance of the instrument was assessed in 350 Chinese
stroke survivors and repeated in 50 patients to examine test-retest reliability.
Questionnaires included a form on demographic and socioeconomic characteristics,
C-ESES, and the Chinese version of the General Self-Efficacy Scale. The AMOS 20.0
and SPSS 17.0 were chosen to evaluate their validity and reliability. RESULTS:
Even though 350 participants answered the questionnaires in the present study,
useful data were obtained from 321 participants (response rate: 91.71%).
Correlation between item and the total scale score (Item-Total Correlation)
ranged from 0.551 to 0.718, indicating that no item needed to be omitted; two
factors, with factor loading 0.620 and 0.806, were obtained from an exploratory
principal components analysis, assuming 59.745% of the total variance. The two
factors were named internal motivation and external motivation. A confirmatory
factor analysis supported the results with a suitable model (chi (5)=291.157;
df=185; P<0.001; root mean square error of approximation =0.044; goodness-of-fit
index =0.938; adjusted goodness-of-fit index =0.914; comparative fit index
=0.858). The C-ESES correlated well with the validated General Self-Efficacy
Scale (r=0.827, P<0.01). Good internal consistency (Cronbach's alpha=0.757 to
0.879) and test-retest reliability (r=0.750, P<0.01) were obtained. CONCLUSION:
The C-ESES is a short, easy to understand, and psychometrically sound measurement
to evaluate exercise self-efficacy in Chinese-speaking stroke survivors.
PMID- 27499615
TI - Alexithymia in patients with type 2 diabetes mellitus: the role of anxiety,
depression, and glycemic control.
AB - OBJECTIVE: This study was aimed at determining the prevalence of alexithymia in
patients with type 2 DM and the factors affecting it. METHODS: This cross
sectional study was conducted with 326 patients with type 2 DM. Study data were
collected with the Personal Information Form, Toronto Alexithymia Scale, and
Hospital Anxiety and Depression Scale. Glycemic control was assessed by glycated
haemoglobin (HbA1c) results. The analysis was performed using descriptive
statistics, chi-square test, Pear-son's correlation, and logistic regression
analysis. RESULTS: Of the patients, 37.7% were determined to have alexithymia. A
significant relationship was determined between alexithymia and HbA1c,
depression, and anxiety. According to binary logistic regression analyses,
alexithymia was 2.63 times higher among those who were in a paid employment than
those who were not, 2.09 times higher among those whose HbA1c levels were >=7.0%
than those whose HbA1c levels were <7.0%, 3.77 times higher among those whose
anxiety subscale scores were >=11 than those whose anxiety subscale scores were
<=10, and 2.57 times higher among those whose depression subscale scores were >=8
than those whose depression subscale scores were <=7. CONCLUSION: In this study,
it was determined that two out of every five patients with DM had alexithymia.
Therefore, their treatment should be arranged to include mental health care
services.
PMID- 27499616
TI - Sex differences in the quality of life of patients with acute coronary syndrome
treated with percutaneous coronary intervention after a 3-year follow-up.
AB - BACKGROUND: The aims of this study were to analyze the dynamics of quality of
life (QoL) changes after 36 months from the percutaneous coronary intervention
(PCI) depending on sex and identify baseline predictors of the follow-up QoL of
patients hospitalized for acute coronary syndrome (ACS) and subjected to PCI.
METHODS AND RESULTS: The study included 137 patients, females (n=67) and males
(n=70), with ACS who underwent PCI. The QoL was assessed using the MacNew Heart
Disease Health-Related Quality of Life questionnaire. The group of females scored
lower in all the domains of the MacNew Heart Disease Health-Related Quality of
Life questionnaire in the initial measurement (B 1), in the measurement after 6
months (B 2), and in the long-term follow-up measurement (36 months - B 3).
Despite the fact that both groups achieved improved QoL, its values were higher
in the males. The average growth rate of the QoL score in the period from the
sixth month to 36th month was higher in females than in males. In the univariate
and multivariate analyses, significant independent predictors with a negative
influence on the long-term QoL score included female sex (rho=-0.190, beta=
0.21), age >60 years (rho=-0.255, beta=-0.186), and diabetes (rho=-0.216, beta=
0.216). CONCLUSION: In a 36-month follow-up of ACS patients treated with PCI,
there were no statistically significant differences in QoL between sexes. In the
entire cohort, there was improvement in QoL, which was higher in the case of the
females studied. For the entire group, significant independent determinants of
lower QoL 3 years after ACS included female sex, age >60 years, and diabetes.
PMID- 27499617
TI - OSG-GEM: Gene Expression Matrix Construction Using the Open Science Grid.
AB - High-throughput DNA sequencing technology has revolutionized the study of gene
expression while introducing significant computational challenges for biologists.
These computational challenges include access to sufficient computer hardware and
functional data processing workflows. Both these challenges are addressed with
our scalable, open-source Pegasus workflow for processing high-throughput DNA
sequence datasets into a gene expression matrix (GEM) using computational
resources available to U.S.-based researchers on the Open Science Grid (OSG). We
describe the usage of the workflow (OSG-GEM), discuss workflow design, inspect
performance data, and assess accuracy in mapping paired-end sequencing reads to a
reference genome. A target OSG-GEM user is proficient with the Linux command line
and possesses basic bioinformatics experience. The user may run this workflow
directly on the OSG or adapt it to novel computing environments.
PMID- 27499618
TI - Legislative and ethical aspects of introducing new technologies in medical care
for senior citizens in developed countries.
AB - INTRODUCTION: The majority of developed countries are currently experiencing
demographic aging. The most frequently expressed concerns related to the changing
age structure are the increased costs of social and medical care, a lack of labor
force in the job market, and financial sustainability of the pension system.
These concerns are often based on the pessimistic view of population aging. This
view understands aging as a prolonged period of illness and suffering. On the
other hand, optimists believe that a longer life span is a result of increased
quality of life and better health care. The quality of life may be improved not
only by medicaments, but also by rapidly developing area of medical devices,
which allow better care for seniors in many areas. AIM: This contribution aims to
assess the legislative environment and ethical questions related to the use of
medical devices, especially medical devices, in medical care for senior citizens.
METHODS: The methods used in this study are literature reviews of legislative and
ethical environment in the European Union (EU) and the US. RESULTS: Main findings
of this study result from assessing the state of medical device regulations in
Europe and the US. Namely, the US regulation seems to be better arranged, which
is probably due to the fact that there is only one responsible body - the US Food
and Drug Administration, which is responsible for all medical device regulations.
On the other hand, in the EU, talks about new legislation are led by ministers
from all the EU member states and it may take a long time before all the EU
countries come to an agreement.
PMID- 27499619
TI - The differential effects of inspiratory, expiratory, and combined resistive
breathing on healthy lung.
AB - Combined resistive breathing (CRB) is the hallmark of obstructive airway disease
pathophysiology. We have previously shown that severe inspiratory resistive
breathing (IRB) induces acute lung injury in healthy rats. The role of expiratory
resistance is unknown. The possibility of a load-dependent type of resistive
breathing-induced lung injury also remains elusive. Our aim was to investigate
the differential effects of IRB, expiratory resistive breathing (ERB), and CRB on
healthy rat lung and establish the lowest loads required to induce injury.
Anesthetized tracheostomized rats breathed through a two-way valve. Varying
resistances were connected to the inspiratory, expiratory, or both ports, so that
the peak inspiratory pressure (IRB) was 20%-40% or peak expiratory (ERB) was 40%
70% of maximum. CRB was assessed in inspiratory/expiratory pressures of 30%/50%,
40%/50%, and 40%/60% of maximum. Quietly breathing animals served as controls. At
6 hours, respiratory system mechanics were measured, and bronchoalveolar lavage
was performed for measurement of cell and protein concentration. Lung tissue
interleukin-6 and interleukin-1beta levels were estimated, and a lung injury
histological score was determined. ERB produced significant, load-independent
neutrophilia, without mechanical or permeability derangements. IRB 30% was the
lowest inspiratory load that provoked lung injury. CRB increased tissue
elasticity, bronchoalveolar lavage total cell, macrophage and neutrophil counts,
protein and cytokine levels, and lung injury score in a dose-dependent manner. In
conclusion, CRB load dependently deranges mechanics, increases permeability, and
induces inflammation in healthy rats. ERB is a putative inflammatory stimulus for
the lung.
PMID- 27499620
TI - A year in the life of German patients with COPD: the DACCORD observational study.
AB - INTRODUCTION: Randomized interventional trials generally recruit highly selected
patients. In contrast, long-term, noninterventional studies can reflect standard
of care of real-life populations. DACCORD (Die ambulante Versorgung mit
langwirksamen Bronchodilatatoren: COPD-Register in Deutschland [Outpatient Care
With Long-Acting Bronchodilators: COPD Registry in Germany]) is an ongoing
observational study, conducted in primary and secondary care in Germany, aiming
to describe the impact of disease and treatments on real-life patients with
chronic obstructive pulmonary disease (COPD). METHODS: Patients had a clinical
and spirometry diagnosis of COPD, were aged >=40 years, and were initiating or
changing COPD maintenance medication. The only exclusion criteria were asthma and
participation in a randomized clinical trial. Exacerbation data were collected
every 3 months. COPD medication, COPD Assessment Test, and forced expiratory
volume in 1 second (FEV1) were recorded at the end of the 1 year period. RESULTS:
In the 6 months prior to baseline, 26.5% of the 3,974 patients experienced >=1
exacerbation, compared with 26.1% over the 1-year follow-up (annualized rate
0.384). Importantly, only previous exacerbations and not poor lung function alone
predicted an increased exacerbation risk. There was a general shift to lower
disease severity from baseline to 1 year, predominantly as a consequence of a
lower proportion of patients considered at high risk due to exacerbations. COPD
Assessment Test mean change from baseline was -1.9, with 48.9% of patients
reporting a clinically relevant improvement. Overall persistence to medication
was high, with 77.2% of patients still receiving the same class of medication at
1 year. CONCLUSION: DACCORD suggests that in clinical practice, the large
majority of COPD patients are symptomatic but seldom exacerbate and that widely
used tools and treatment recommendations do not reflect this fully.
PMID- 27499621
TI - Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle
encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c
mice.
AB - Our previous studies have established the efficacy of chemopreventive regimens of
aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs)
in combination with free sulforaphane (ACS combination) to prevent or delay the
initiation and progression of pancreatic cancer, classified as one of the
deadliest diseases with very low chances of survival upon diagnosis. Although
toxicity of individual drugs and SLN has been studied previously, there are no
studies in current literature that evaluate the potential toxicity of a combined
regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs).
Hence, objective of the current study was to investigate the potential toxic
effects of ACS c-SLN combined chemopreventive regimens following acute (3 days),
subacute (28 days), and subchronic (90 days) administrations by oral gavage in
BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN,
low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg),
and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated
based on animal survival, body weight, hematology, blood chemistry, and organ
histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths
were observed. Treatment with ACS c-SLNs did not cause alteration in complete
blood counts and blood chemistry data. Histopathological examination of various
organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based
on the results of this study, no signs of toxicity in acute, subacute, and
subchronic studies following oral administration of ACS c-SLNs were found
indicating that the oral dosing regimens were safe at the levels tested for long
term administration to prevent the onset of pancreatic cancer.
PMID- 27499622
TI - Proretinal nanoparticles: stability, release, efficacy, and irritation.
AB - Despite many potent biological activities, retinoids such as retinoic acid (RA)
and retinal possess dose-related broad side effects. In this study, we show that
this problem, which has been unsolvable for a long time, can be tackled through a
controlled release strategy in which retinal is continuously delivered to the
skin via sustained release from proretinal nanoparticles. The water dispersible
proretinal nanoparticles are stable when kept in water at neutral pH and at room
temperature for 8 months under light-proof conditions, and show sustained release
of retinal into human synthetic sebum at a pH of 5. In the daily topical
application tests performed for 4 weeks on rats' skin, the nanoparticles showed
superior ability to increase epidermal thickness compared to RA and retinal, with
no skin irritation observed for the proretinal particles, but severe skin
irritation observed for RA and free retinal. When tested under occlusion
conditions in human volunteers, insignificant skin irritation was observed for
the proretinal nanoparticles. The 12-week, double-blind, split-face study on
human volunteers indicates better antiaging efficacy of the particles as compared
to the free RA.
PMID- 27499624
TI - Endothelial glycocalyx conditions influence nanoparticle uptake for passive
targeting.
AB - Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and
coincide with EC glycocalyx coat shedding. These diseases may be prevented by
delivering medications to affected vascular regions using circulating
nanoparticle (NP) drug carriers. The objective of the present study was to
observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP)
to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad
endothelial cells were chosen for their robust glycocalyx, verified by
fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate
(HS) chains. Confocal fluorescent imaging revealed a ~3 um thick glycocalyx
layer, covering 75% of the ECs and containing abundant HS. This healthy
glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores
are typically 7 nm wide. Additional glycocalyx models tested included: a
collapsed glycocalyx obtained by culturing cells in reduced protein media, a
degraded glycocalyx obtained by applying heparinase III enzyme to specifically
cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into
the media after enzyme degradation. The collapsed glycocalyx was2 um thick with
unchanged EC coverage and sustained HS content. The degraded glycocalyx showed
similar changes in EC thickness and coverage but its HS thickness was reduced to
0.7 um and spanned only 10% of the original EC surface. Both dysfunctional models
retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The
collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular
spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the
glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2
um and 44% coverage of the ECs, but it was able to reverse the NP uptake back to
baseline levels. In summary, this study showed that the glycocalyx structure is
critical for NP uptake by ECs and may serve as a passive pathway for delivering
NPs to dysfunctional ECs.
PMID- 27499623
TI - Nanobody-derived nanobiotechnology tool kits for diverse biomedical and
biotechnology applications.
AB - Owing to peculiar properties of nanobody, including nanoscale size, robust
structure, stable and soluble behaviors in aqueous solution, reversible
refolding, high affinity and specificity for only one cognate target, superior
cryptic cleft accessibility, and deep tissue penetration, as well as a
sustainable source, it has been an ideal research tool for the development of
sophisticated nanobiotechnologies. Currently, the nanobody has been evolved into
versatile research and application tool kits for diverse biomedical and
biotechnology applications. Various nanobody-derived formats, including the
nanobody itself, the radionuclide or fluorescent-labeled nanobodies, nanobody
homo- or heteromultimers, nanobody-coated nanoparticles, and nanobody-displayed
bacteriophages, have been successfully demonstrated as powerful
nanobiotechnological tool kits for basic biomedical research, targeting drug
delivery and therapy, disease diagnosis, bioimaging, and agricultural and plant
protection. These applications indicate a special advantage of these nanobody
derived technologies, already surpassing the "me-too" products of other
equivalent binders, such as the full-length antibodies, single-chain variable
fragments, antigen-binding fragments, targeting peptides, and DNA-based aptamers.
In this review, we summarize the current state of the art in nanobody research,
focusing on the nanobody structural features, nanobody production approach,
nanobody-derived nanobiotechnology tool kits, and the potentially diverse
applications in biomedicine and biotechnology. The future trends, challenges, and
limitations of the nanobody-derived nanobiotechnology tool kits are also
discussed.
PMID- 27499625
TI - The major risk factors for delirium in a clinical setting.
AB - OBJECTIVE: We aimed to determine the major risk factors for the development of
delirium in patients at a single general hospital by comparison with a control
group. SUBJECTS AND METHODS: We reviewed the medical records of 260 delirium
patients and 77 control patients. We investigated age, sex, and risk factors for
delirium in the total delirium group (n=260), the delirium medical subgroup
(n=142), and the delirium surgical subgroup (n=118). Logistic regression analysis
adjusting for age and sex was performed to identify the odds ratio. RESULTS: The
mean age and the percentage of males were significantly higher in the delirium
group compared with the control group (68.9 vs 54.3 years and 70% vs 41.6%,
respectively). Risk factors for the delirium group were lower plasma albumin,
hypertension, mechanical ventilation, and antipsychotic drug use. Plasma sodium
level and hypertension were important risk factors for the delirium medical
subgroup. Stroke history, hypertension, ICU care, and medication were important
risk factors for the delirium surgical subgroup. CONCLUSION: Lower plasma
albumin, hypertension, mechanical ventilation, and antipsychotic drug use are
important risk factors for delirium.
PMID- 27499627
TI - Correction to "Breast Volume Asymmetry Value, Ratio, and Cancer Risk".
AB - [This corrects the article on p. 87 in vol. 9, PMID: 26691819.].
PMID- 27499626
TI - Effect of biological factors on successful measurements with skeletal-muscle (1)H
MRS.
AB - BACKGROUND: Our purpose in this study was to clarify whether differences in
subject group attributes could affect data acquisition in proton magnetic
resonance spectroscopy ((1)H-MRS). METHODS: Subjects without diabetes mellitus
(DM) were divided into two groups (group A, in their 20s; group B, 30-60 years
old). Subjects with DM formed group C (30-60 years old). The numbers of subjects
were 19, 27, and 22 for group A, B, and C respectively. For all subjects, (1)H
MRS measurements were taken of the soleus muscle (SOL) and the anterior tibial
muscle (AT). We defined the success of the measurements by the detection of
intramyocellular lipids. Moreover, we also measured the full width at half
maximum of the water peaks for all subjects. RESULTS: The success rate was
significantly higher for the AT (100%) than for the SOL (81.6%) (P<0.01). For the
SOL, the success rate was 100% in group A, 85.2% in group B, and 77.3% in group
C. There was a significant difference (P<0.05) between groups A and B, as well as
between groups A and C. In all subjects, there was a significant difference
(P<0.01) in the full width at half maximum (Hz) of the water peak between the AT
and SOL measurements. CONCLUSION: We conclude that differences in the age and DM
history of subjects could affect the probability of successful (1)H-MRS data
acquisition.
PMID- 27499628
TI - Theoretical domains framework to assess barriers to change for planning health
care quality interventions: a systematic literature review.
AB - BACKGROUND: Theoretical domains framework (TDF) provides an integrative model for
assessing barriers to behavioral changes in order to suggest interventions for
improvement in behavior and ultimately outcomes. However, there are other tools
that are used to assess barriers. OBJECTIVE: The objective of this study is to
determine the degree of concordance between domains and constructs identified in
two versions of the TDF including original (2005) and refined version (2012) and
independent studies of other tools. METHODS: We searched six databases for
articles that studied barriers to health-related behavior changes of health care
professionals or the general public. We reviewed quantitative papers published in
English which included their questionnaires in the article. A table including the
TDF domains of both original and refined versions and related constructs was
developed to serve as a reference to describe the barriers assessed in the
independent studies; descriptive statistics were used to express the results.
RESULTS: Out of 552 papers retrieved, 50 were eligible to review. The barrier
domains explored in these articles belonged to two to eleven domains of the
refined TDF. Eighteen articles (36%) used constructs outside of the refined
version. The spectrum of barrier constructs of the original TDF was broader and
could meet the domains studied in 48 studies (96%). Barriers in domains of
"environmental context and resources", "beliefs about consequences", and "social
influences" were the most frequently explored in 42 (84%), 37 (74%), and 33 (66%)
of the 50 articles, respectively. CONCLUSION: Both refined and original TDFs
cataloged barriers measured by the other studies that did not use TDF as their
framework. However, the original version of TDF explored a broader spectrum of
barriers than the refined version. From this perspective, the original version of
the TDF seems to be a more comprehensive tool for assessing barriers in practice.
PMID- 27499629
TI - Nab-paclitaxel and trastuzumab combination: a promising approach for neoadjuvant
treatment in HER2-positive breast cancer.
AB - Neoadjuvant therapy is a well-established approach for the treatment of locally
advanced or inflammatory breast cancer (BC) and has been increasingly used in
recent years not only as a management strategy but also as a research tool.
Recently, nanoparticle albumin-bound paclitaxel (nab-paclitaxel)/trastuzumab
combinations have been associated with promising activity in different clinical
settings. In the present case, we report a complete pathological response after
neoadjuvant treatment with the trastuzumab/nab-paclitaxel combination in a
locally advanced human epidermal growth factor receptor 2 (HER2)-positive BC
patient, with a good toxicity profile. This combination may represent a valid
therapeutic option in the neoadjuvant therapy for HER2-positive locally advanced
BC.
PMID- 27499630
TI - Inhibition of microRNA-126 promotes the expression of Spred1 to inhibit
angiogenesis in hepatocellular carcinoma after transcatheter arterial
chemoembolization: in vivo study.
AB - MicroRNA-126 (miR-126) has been found to promote angiogenesis, but the underlying
mechanisms are still unclear. So, we conducted this study to explore the effect
of miR-126 expression on angiogenesis in hepatocellular carcinoma (HCC) after
transcatheter arterial chemoembolization (TACE). The expression levels of miR-126
and sprouty-related, EVH1 domain containing protein (Spred)1 in surgically
resected HCC tissue, HCC tissue with TACE + operation, and tumor-adjacent tissues
were determined by quantitative real-time polymerase chain reaction. The
expression levels of miR-126, Spred1, and vascular endothelial growth factor were
found by quantitative real-time polymerase chain reaction and Western blot. The
microvessel density (MVD) of tumor tissues was determined by immunohistochemical
staining. The miR-126 and Spred1 expressions in HCC tissue with TACE + operation
were elevated and decreased, respectively, as compared to those in surgically
resected HCC tissues and tumor-adjacent tissues (all P<0.001), which indicated
that the expression of Spred1 was negatively correlated with miR-126 (P<0.001, r=
0.6224). Based on the bioinformatics analysis and luciferase reporter gene
activity detection, Spred1 was found to target miR-126 (P<0.001). Inhibition of
miR-126 expression reduces the degree of weight loss and tumor size in TACE model
rats. The MVD in TACE + operation group was increased compared to that in the
control group; inhibition of miR-126 expression had a reversal effect, to a
certain extent, on MVD increase after TACE (all P<0.05). Inhibition of miR-126
expression increased Spred1 expression and decreased vascular endothelial growth
factor expression (P<0.01). In summary, this study unveiled the potential
mechanism by which miR-126 regulates angiogenesis in HCC tissues through
embolization treatment by targeting Spred1, and also showed that the feasibility
of TACE with the miR-126 inhibitor has a certain value in the medical treatment
of HCC.
PMID- 27499631
TI - Coffee consumption and risk of hepatocellular carcinoma: a meta-analysis of
eleven epidemiological studies.
AB - Growing evidence has shown that coffee consumption is inversely related with the
risk of hepatocellular carcinoma. It is suggested that caffeine maintains strong
antioxidative activity. With this property, coffee intake may lead to the
inhibition of cell proliferation of liver cancer cells; also, some compounds
contained in coffee can reduce the genotoxicity of aflatoxin B1 in vitro and
lower the damage caused by some carcinogens. A computerized search was performed
in PubMed to identify relevant articles published before August 2015. Eleven
relevant studies were included with a total of 2,795 cases and 340,749 control
subjects. According to the meta-analysis we performed, the pooled odds ratio (OR)
from all included studies was 0.49 (95% confidence interval [CI] =0.46-0.52). The
subgroup analysis indicated that the pooled ORs for Asian studies and other
populations were 0.27 (95% CI =0.23-0.31) and 0.82 (95% CI =0.77-0.87),
respectively. The overall pooled OR for high consumption was decreased to 0.21
(95% CI =0.18-0.25) and significance was observed. Among other populations, the
pooled OR of subjects with high coffee consumption was 0.65 (95% CI =0.56-0.73)
compared to the nondrinker. The corresponding OR of five Asian studies was 0.13
(95% CI =0.09-0.17). The findings from this meta-analysis further confirmed the
inverse association between the coffee consumption and hepatocellular carcinoma
risk with quantitative evidence. The protective effect can be detected among
healthy population and patients with chronic liver diseases, and the consumption
can also prevent the development of liver cirrhosis.
PMID- 27499632
TI - The expression status of TRX, AR, and cyclin D1 correlates with
clinicopathological characteristics and ER status in breast cancer.
AB - BACKGROUND: The ER signaling pathway plays a critical role in breast cancer. ER
signaling pathway-related proteins, such as TRX, AR, and cyclin D1, may have an
important function in breast cancer. However, the ways that they influence breast
cancer development and progression are still unclear. PATIENTS AND METHODS: A
total of 101 Chinese female patients diagnosed with invasive ductal breast
adenocarcinoma were retrospectively enrolled in the study. The expression levels
of TRX, AR, and cyclin D1 were detected by immunohistochemistry and analyzed via
correlation with clinicopathological characteristics and the expression status of
ER, PR, and HER2. RESULTS: The expression status of TRX, AR, and cyclin D1 was
not associated with the patient's age, menopausal status, tumor size, or
histological differentiation (P>0.05), but was positively correlated with ER and
PR (P<0.001, respectively). Most (66/76, 86.8) TRX-positive patients were also
HER2-positive (P=0.003). Of AR- or cyclin D1-positive patients, most had
relatively earlier I-II tumor stage (P=0.005 and P=0.047, respectively) and no
metastatic lymph node involvement (P=0.008 and P=0.005, respectively).
CONCLUSION: TRX was found to be positively correlated with ER and PR expression,
whereas it was negatively correlated with HER2 expression. In addition, we found
that the positive expression of AR and cyclin D1 was correlated with lower TNM
stage and fewer metastatic lymph nodes, and it was more common in ER-positive
breast cancer than in the basal-like subtype. This may indicate that AR and
cyclin D1 are good predictive and prognostic factors and closely interact with ER
signaling pathway. Further studies will be necessary to investigate the response
and clinical outcomes of treatment targeting TRX, AR, and cyclin D1.
PMID- 27499633
TI - MK-2206 co-treatment with 5-fluorouracil or doxorubicin enhances chemosensitivity
and apoptosis in gastric cancer by attenuation of Akt phosphorylation.
AB - The anticancer effect of MK-2206, an Akt inhibitor, has been explored in some
types of cancers, but its effect on gastric cancer is unclear. In this study, we
aimed to investigate its anticancer effect in gastric cancer cells. Cell
viability and colony formation assays showed that MK-2206 effectively inhibited
the proliferation of SGC-7901 and MKN45 cells. The 50% inhibitory concentration
values after 24, 48, and 72 hours' treatment were 22.92, 13.68, and 8.55 MUM in
SGC-7901 cells and 19.21, 13.10, and 9.11 MUM in MKN45 cells, respectively.
Treatment with MK-2206 induced apoptosis in SGC-7901 cells as indicated by flow
cytometry assay. The combination indexes of MK-2206 and doxorubicin were 0.59 in
SGC-7901 cells and 0.57 in MKN45 cells, whereas for 5-fluorouracil (5-FU) the
indexes were 0.17 in SGC-7901 cells and 0.73 in MKN45 cells, indicating that MK
2206 could work synergistically with doxorubicin or 5-FU to inhibit cell growth.
Furthermore, a small dose (1 MUM) of MK-2206 co-treatment with doxorubicin or 5
FU was sufficient for complete inhibition of chemotherapeutic alteration of
phosphorylated Akt expression and significant enhancement of pro-apoptosis effect
through the activation of caspase pathway. Therefore, MK-2206 effectively
inhibits gastric cancer cell growth by attenuation of Akt phosphorylation and
synergistically enhances the antitumor effect of doxorubicin and 5-FU via caspase
dependent apoptosis.
PMID- 27499634
TI - FAT10 is associated with the malignancy and drug resistance of non-small-cell
lung cancer.
AB - Lung cancer has become one of the leading causes of cancer mortality worldwide,
and non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer
cases. Currently, platinum-based chemotherapy drugs, including cisplatin and
carboplatin, are the most effective treatment for NSCLC. However, the clinical
efficacy of chemotherapy is markedly reduced later in the treatment because drug
resistance develops during the treatment. Recently, a series of studies has
suggested the involvement of FAT10 in the development and malignancy of multiple
cancer types. In this study, we focused our research on the function of FAT10 in
NSCLC, which has not been previously reported in the literature. We found that
the expression levels of FAT10 were elevated in quick chemoresistance NSCLC
tissues, and we demonstrated that FAT10 promotes NSCLC cell proliferation,
migration, and invasion. Furthermore, the protein levels of FAT10 were elevated
in cisplatin- and carboplatin-resistant NSCLC cells, and knockdown of FAT10
reduced the drug resistance of NSCLC cells. In addition, we gained evidence that
FAT10 regulates NSCLC malignancy and drug resistance by modulating the activity
of the nuclear factor kappa B signaling pathway.
PMID- 27499636
TI - JAK2 inhibitor combined with DC-activated AFP-specific T-cells enhances antitumor
function in a Fas/FasL signal-independent pathway.
AB - OBJECTIVE: Combination therapy for cancer is more effective than using only
standard chemo- or radiotherapy. Our previous results showed that dendritic cell
activated alpha-fetoprotein (AFP)-specific T-cells inhibit tumor in vitro and in
vivo. In this study, we focused on antitumor function of CD8(+) T-cells combined
with or without JAK2 inhibitor. METHODS: Proliferation and cell cycle were
analyzed by CCK-8 and flow cytometry. Western blot was used to analyze the
expression level of related protein and signaling pathway. RESULTS: We
demonstrated reduced viability and induction of apoptosis of tumor cells with
combination treatment. Intriguingly, cell cycle was blocked at the G1 phase by
using AFP-specific CD8(+) T-cells combined with JAK2 inhibitor (AG490).
Furthermore, an enhanced expression of BAX but no influence on Fas/FasL was
detected from the tumor cells. CONCLUSION: These results indicate a Fas/FasL
independent pathway for cellular apoptosis in cancer therapies with the treatment
of AFP-specific CD8(+) T-cells combined with JAK2 inhibitor.
PMID- 27499635
TI - Functions and mechanisms of long noncoding RNAs in lung cancer.
AB - Lung cancer is a heterogeneous disease, and there is a lack of adequate
biomarkers for diagnosis. Long noncoding RNAs (lncRNAs) are emerging as an
important set of molecules because of their roles in various key
pathophysiological pathways, including cell growth, apoptosis, and metastasis. We
review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of
lncRNAs in lung cancer have increased the number of potential effective
biomarkers, thus providing options to increase the therapeutic benefit. In this
review, we summarize the functions, mechanisms, and regulatory networks of
lncRNAs in lung cancer, providing a basis for further research in this field.
PMID- 27499637
TI - Congenital anomalies of the genitourinary system can help in diagnosis of the
primary site of metastatic cancer: a case report and a review of the literature.
AB - OBJECTIVE: To analyze whether the presence of congenital anomalies of the
genitourinary system that are accompanied by specific types of cancer and
predispose patients to many complications, including infection, obstruction,
stasis, calculus formation, and impaired renal function, could help in the
diagnosis of the primary site of a metastatic tumor. CASE PRESENTATION: We report
a case of a 58-year-old man with metastatic adenocarcinoma, in whom congenital
anomalies of the genitourinary system proved helpful for the diagnosis of the
primary site of cancer originating in the seminal vesicles. CONCLUSION: We report
an extremely rare case of primary adenocarcinoma arising probably from the left
seminal vesicle associated with ipsilateral renal agenesis. The lesion was
detected on ultrasound and contrast-enhanced computed tomography and confirmed
histologically with ultrasound-guided biopsy. Serum markers, ie, CA19-9 and
CA125, were elevated, while prostate-specific antigen and carcinoembryonic
antigen were within normal limits. Such a constellation of markers strengthened
the diagnosis. Our patient unfortunately presented very late in the course of the
disease. Hence, we decided to initiate antiandrogen therapy and best supportive
care in a hospice setting. Only early detection seems to be the key factor that
may result in improved cure rates for cancer of the seminal vesicles. We also
performed a literature search for current concepts related to the diagnosis and
clinical management of primary adenocarcinoma of seminal vesicles.
PMID- 27499638
TI - Targeting breast cancer stem cells by dendritic cell vaccination in humanized
mice with breast tumor: preliminary results.
AB - BACKGROUND: Breast cancer (BC) is one of the leading cancers in women. Recent
progress has enabled BC to be cured with high efficiency. However, late detection
or metastatic disease often renders the disease untreatable. Additionally,
relapse is the main cause of death in BC patients. Breast cancer stem cells
(BCSCs) are considered to cause the development of BC and are thought to be
responsible for metastasis and relapse. This study aimed to target BCSCs using
dendritic cells (DCs) to treat tumor-bearing humanized mice models. MATERIALS AND
METHODS: NOD/SCID mice were used to produce the humanized mice by transplantation
of human hematopoietic stem cells. Human BCSCs were injected into the mammary fat
pad to produce BC humanized mice. Both hematopoietic stem cells and DCs were
isolated from the human umbilical cord blood, and immature DCs were produced from
cultured mononuclear cells. DCs were matured by BCSC-derived antigen incubation
for 48 hours. Mature DCs were vaccinated to BC humanized mice with a dose of
10(6) cells/mice, and the survival percentage was monitored in both treated and
untreated groups. RESULTS: The results showed that DC vaccination could target
BCSCs and reduce the tumor size and prolong survival. CONCLUSION: These results
suggested that targeting BCSCs with DCs is a promising therapy for BC.
PMID- 27499639
TI - Lapatinib induces autophagic cell death and differentiation in acute myeloblastic
leukemia.
AB - Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth
factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity.
In this study, we examined the effects and mechanism of action of lapatinib on
several human leukemia cells lines, including acute myeloid leukemia (AML),
chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We
found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML
KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib
induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell
death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused
autophagic cell death as shown by positive acridine orange staining, the massive
formation of vacuoles as seen by electronic microscopy, and the upregulation of
LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3
methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA
(shRNA) partially rescued lapatinib-induced cell death. In addition, the
induction of phagocytosis and ROS production as well as the upregulation of
surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells,
suggesting the induction of macrophagic differentiation in AML U937 cells by
lapatinib. We also noted the synergistic effects of the use of lapatinib and
cytotoxic drugs in U937 leukemia cells. These results indicate that lapatinib may
have potential for development as a novel antileukemia agent.
PMID- 27499640
TI - Mast cells positive to tryptase, endothelial cells positive to protease-activated
receptor-2, and microvascular density correlate among themselves in
hepatocellular carcinoma patients who have undergone surgery.
AB - BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several
proangiogenic cytokines stored in their cytoplasm. In particular MCs can release
tryptase, a potent in vivo and in vitro proangiogenic factor via proteinase
activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase
phosphorylation. Nevertheless, no data are available concerning the relationship
between MC density positive to tryptase (MCDPT), endothelial cells positive to
PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in
hepatocellular carcinoma (HCC) angiogenesis. This study analyzed the correlation
between MCDPT, PAR-2-MVD, and C-MVD, each correlated to the others and to the
main clinicopathological features, in early HCC patients who underwent surgery.
METHODS: A series of 53 HCC patients with early stage (stage 0 according to the
Barcelona Clinic Liver Cancer Staging Classification) were selected and then
underwent surgery. Tumor tissue samples were evaluated by means of
immunohistochemistry and image analysis methods in terms of number of MCDPT, PAR
2-MVD, and C-MVD. RESULTS: A significant correlation between MCDPT, PAR-2-MVD,
and C-MVD groups, each correlated to the others, was found by Pearson t-test
analysis (r ranged from 0.67 to 0.81; P-value ranged from 0.01 to 0.03). No other
significant correlation was found. CONCLUSION: Our in vivo pilot data suggest
that MCDPT and PAR-2-MVD may play a role in HCC angiogenesis and could be further
evaluated as a target of antiangiogenic therapy.
PMID- 27499641
TI - Association between cyclin D1 G870A polymorphism and hepatocellular carcinoma
risk: a meta-analysis.
AB - BACKGROUND: Cyclin D1 (CCND1) G870A polymorphism may be associated with
hepatocellular carcinoma (HCC) risk, but the results of previous studies were
inconsistent. Available evidence was meta-analyzed to assess their potential
association. METHODS: Databases PubMed, EMBASE, Cochrane Library, Web of Science,
Chinese Biomedical Literature database, China National Knowledge Infrastructure,
and Google Scholar were systematically searched. Meta-analyses were performed to
investigate the association of G870A polymorphism with HCC risk by calculating
odds ratios (ORs) and 95% confidence intervals (CIs) from the data of relevant
case-control studies. RESULTS: Results of this meta-analysis of six case-control
studies involving 1,030 cases and 1,683 controls indicate that G870A polymorphism
was not associated with HCC risk in any of the five genetic models tested
(recessive model: AA vs GG + AG: OR =1.38, 95% CI =0.95-2.00, P=0.09; dominant
model: AG + AA vs GG: OR =1.38, 95% CI =0.87-2.20, P=0.17; homozygous model: AA
vs GG: OR =1.60, 95% CI =0.87-2.94, P=0.13; heterozygous model: AG vs GG: OR
=1.24, 95% CI =0.86-1.79, P=0.25; allelic model: A vs G: OR =1.30, 95% CI =0.95
1.80, P=0.10). Subgroup analyses according to ethnicity showing marginally
significant association between this single nucleotide polymorphism and HCC risk
indicate that G870A may be significantly associated with HCC risk in Caucasian
populations (recessive model: AA vs GG + AG: OR =2.34, 95% CI =1.60-3.42,
P<0.0001; dominant model: AG + AA vs GG: OR =2.44, 95% CI =1.19-4.97, P=0.01;
homozygous model: AA vs GG: OR =3.42, 95% CI =1.80-6.50, P=0.0002; allelic model:
A vs G: OR =2.06, 95% CI =1.31-3.24, P=0.002), but not in Asian populations.
CONCLUSION: Available evidence suggests that no significant association between
G870A polymorphism and HCC risk was found in either total populations or Asian
populations. However, significant association was found in Caucasian populations.
These results should be verified and extended in further detailed and well
designed studies involving larger, multiethnic samples.
PMID- 27499642
TI - Stigmatization and self-perception in children with atopic dermatitis.
AB - Atopic dermatitis (AD) is one of the most common skin diseases. Prevalence of AD
is highest in childhood. Because of chronicity and often visible lesions, AD may
lead to stigmatization and problems with self-perception. However, problems of
self-perception and stigmatization in AD children are poorly studied. Literature
data on general tendencies of children's development, clinical course, and
epidemiologic tendencies of AD in different age groups make it possible to
highlight three main periods in the formation of self-perception and
stigmatization. The first period is from early infancy till 3 years of age. The
child's problems in this period depend on parental exhaustion, emotional
distress, and security of the mother-child attachment. The child's AD may form a
kind of vicious circle in which severe AD causes parental distress and exhaustion
that in turn lead to exacerbation of AD and psychological problems in children.
The second period is from 3 till 10 years of age. During this period, development
of AD children may be influenced by teasing, bullying, and avoiding by their
peers. However, the majority of children in this age group are very optimistic.
The third period is from 10 years till adulthood. Problems related to low self
esteem are characteristic during this period. It is important to identify
children with AD and their parents who need psychological help and provide them
with needs-based consultation and care. Appropriate treatment, medical
consultations, and educational programs may help to reduce emotional problems in
AD children and their parents.
PMID- 27499643
TI - Mevalonate kinase deficiency: current perspectives.
AB - Mevalonate kinase deficiency (MKD) is a recessively inherited autoinflammatory
disorder with a spectrum of manifestations, including the well-defined clinical
phenotypes of hyperimmunoglobulinemia D and periodic fever syndrome and mevalonic
aciduria. Patients with MKD have recurrent attacks of hyperinflammation
associated with fever, abdominal pain, arthralgias, and mucocutaneous lesions,
and more severely affected patients also have dysmorphisms and central nervous
system anomalies. MKD is caused by mutations in the gene encoding mevalonate
kinase, with the degree of residual enzyme activity largely determining disease
severity. Mevalonate kinase is essential for the biosynthesis of nonsterol
isoprenoids, which mediate protein prenylation. Although the precise pathogenesis
of MKD remains unclear, increasing evidence suggests that deficiency in protein
prenylation leads to innate immune activation and systemic hyperinflammation.
Given the emerging understanding of MKD as an autoinflammatory disorder, recent
treatment approaches have largely focused on cytokine-directed biologic therapy.
Herein, we review the current genetic and pathologic understanding of MKD, its
various clinical phenotypes, and the evolving treatment approach for this
multifaceted disorder.
PMID- 27499644
TI - Animal models of GM2 gangliosidosis: utility and limitations.
AB - GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a
deficiency of the glycohydrolase, beta-N-acetylhexosaminidase, and includes the
closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents
the normal, stepwise degradation of ganglioside, which accumulates unchecked
within the cellular lysosome, particularly in neurons. As a result, individuals
with GM2 gangliosidosis experience progressive neurological diseases including
motor deficits, progressive weakness and hypotonia, decreased responsiveness,
vision deterioration, and seizures. Mice and cats are well-established animal
models for Sandhoff disease, whereas Jacob sheep are the only known laboratory
animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human
diseases are relatively rare, animal models are indispensable tools for further
study of pathogenesis and for development of potential treatments. Though no
effective treatments for gangliosidoses currently exist, animal models have been
used to test promising experimental therapies. Herein, the utility and
limitations of gangliosidosis animal models and how they have contributed to the
development of potential new treatments are described.
PMID- 27499645
TI - First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in
Advanced Solid Tumors.
AB - PURPOSE: Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs)
release factors, suppressing the growth of cancer cells and prolonging survival
in spontaneous or induced tumor animals, mediated, in part, by increased levels
of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The
primary objective of this study was to determine the safety of RMBs in advanced,
treatment-resistant metastatic cancers, and then its efficacy (survival), which
is the secondary objective. METHODS: Thirty-one patients underwent up to four
intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in
this single-arm trial (FDA BB-IND 10091; NCT 00283075). Serial physical
examinations, laboratory testing, and PET-CT imaging were performed before and
three months after each implant. RESULTS: RMBs were well tolerated at both dose
levels (mean 660.9 per implant). AEs were (Grade 1/2) with no treatment-related
SAEs. CONCLUSION: The data support the safety of RMB therapy in advanced
malignancy patients, and the preliminary evidence for their potential efficacy is
encouraging. A Phase 2 efficacy trial is ongoing.
PMID- 27499646
TI - Design and methods for a Scandinavian pharmacovigilance study of osteonecrosis of
the jaw and serious infections among cancer patients treated with antiresorptive
agents for the prevention of skeletal-related events.
AB - OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a recognized complication of potent
antiresorptive therapies, especially at the doses indicated to prevent skeletal
complications for cancer patients with bone metastases. This paper describes the
rationale and methods for a prospective, post-authorization safety study of
cancer patients treated with antiresorptive therapies. METHODS: As part of a
comprehensive pharmacovigilance plan, developed with regulators' input, the study
will estimate incidence of ONJ and of serious infections among adult cancer
patients with bone metastases treated with denosumab (120 mg subcutaneously) or
zoledronic acid (4 mg intravenously, adjusted for renal function). Patients will
be identified using routinely collected data combined with medical chart review
in Denmark, Sweden, and Norway. Followup will extend from the first
administration of antiresorptive treatment to the earliest of death, loss-to
follow-up, or 5 years after therapy initiation. Results will be reported for
three treatment cohorts: denosumab-naive patients, zoledronic acid-naive
patients, and patients who switch from bisphosphonate treatment to denosumab. ONJ
cases will be identified in three newly established national ONJ databases and
adjudicated by the committee that functioned during the XGEVA((r)) clinical
trials program. CONCLUSION: This study will provide a real world counterpart to
the clinical trial-estimated risks for ONJ and serious infections for cancer
patients initiating denosumab or zoledronic acid. The establishment of ONJ
databases in the three Scandinavian countries will have potential benefits
outside this study for the elucidation of ONJ risk factors and the evaluation of
ONJ treatment strategies.
PMID- 27499647
TI - Combined uterine and urinary bladder rupture: an unusual complication of
obstructed labor in a primigravida.
AB - BACKGROUND: Combined uterine and urinary bladder rupture following prolonged
obstructed labor is indeed a momentous uro-obstetric emergency. The urinary
bladder involvement is distinctly rare in the absence of factors that predispose
the bladder to be adherent to the lower uterine segment and is quite unusual in a
primigravida. OBJECTIVE: To report a rare case of uterine rupture involving
urinary bladder secondary to a prolonged obstructed labor in a primigravida from
a low resource setting. CASE: A 17-year-old married unbooked primigravida who
presented with a 3-day history of spontaneous onset of labor at term that was
initially managed at home and later in a primary health care center where she had
fundal pressure and oxytocin augmentation, respectively. The labor was
complicated by combined uterine and urinary bladder rupture with sepsis. She was
resuscitated and had exploratory laparotomy with uterine and urinary bladder
repair. The postoperative period was uneventful and she was followed-up at the
gynecology and family planning clinics. CONCLUSION: There is a need for community
reawakening on the inherent risks of teenage pregnancy, bad obstetric practices,
and unsupervised pregnancy, labor, and delivery, particularly in the rural
settings as in the index patient. A high index of suspicion and prompt
appropriate intervention will reduce the sequel of morbidity and occasional
mortality from this predicament.
PMID- 27499648
TI - The experiences of women with polycystic ovary syndrome on a very low-calorie
diet.
AB - Polycystic ovary syndrome (PCOS) is variously reported to affect between 5% and
26% of reproductive age women in the UK and accounts for up to 75% of women
attending fertility clinics due to anovulation. The first-line treatment option
for overweight/obese women with PCOS is diet and lifestyle interventions.
However, optimal dietary guidelines are missing, with very little research having
been done in this area. This paper presents the findings from a qualitative study
(using semistructured interviews) of ten obese women who had PCOS and who had
used LighterLife Total (LLT), a commercial weight loss program which utilizes a
very low-calorie diet in conjunction with behavioral change therapy underpinned
by group support. We investigated the women's history of obesity, their
experiences of other diets compared with LLT, and the on-going impact that this
has had on their lives. Findings show that most women reported greater success
using this weight loss program in terms of achieving and maintaining weight loss
when compared with other diets. Furthermore, all the women nominated LLT as their
model weight loss intervention with only a few modifications.
PMID- 27499650
TI - A newborn with very rare von Voss-Cherstvoy syndrome: a case report.
AB - INTRODUCTION: von Voss-Cherstvoy syndrome is a part of a group of syndromes with
radial and hematologic abnormalities, and until now approximately ten cases have
been reported in the literature. This syndrome is characterized by a triad of
radial ray defects, occipital encephalocele, and urogenital abnormalities. CASE
PRESENTATION: We report a neonate from Indian ethnicity who was diagnosed with
von Voss-Cherstvoy syndrome. The neonate had radial ray defect, occipital
encephalocele, tetralogy of Fallot, and bilateral agenesis of kidney, ureter, and
bladder. The neonate was suspected to have von Voss-Cherstvoy syndrome on the
basis of clinical features, which was further confirmed by fibroblast analysis
showing somatic mosaicism for del(13q). CONCLUSION: von Voss-Cherstvoy syndrome
is a very rare syndrome that can be suspected on the basis of typical clinical
features and confirmed by fibroblast analysis showing somatic mosaicism for
del(13q). This adds a second case of this chromosome anomaly described in this
syndrome.
PMID- 27499651
TI - New developments in the treatment of early-onset spinal deformity: role of the
Shilla growth guidance system.
AB - Early-onset scoliosis is a complex condition with multiple facets. The goal of
treating any spinal deformity is to improve the condition of the patient with the
least intervention necessary. A system that allows for continuation of natural
spinal growth while correcting the deformity should be the goal of treating this
complex condition. The SHILLA growth guidance system allows for continued growth
of the pediatric spine while correcting and guiding the apex and guiding the
future growth of the curvature. The system involves selective fusion across the
apex of the curvature, and minimally invasive instrumentation is then used above
and below the apex to allow for continued growth of the spine. A review of recent
literature on the SHILLA growth guidance system shows promising results. Early
animal models showed continued growth across unfused levels with minimal facet
articular damage. Comparative studies to traditional growing rods showed
significantly less total surgeries along with comparable correction and
longitudinal growth. The SHILLA growth guidance system is a good option for this
complex patient group. Results are comparable with other growing constructs with
significantly less operative interventions. The SHILLA system allows for natural
growth of the pediatric spine while correcting the scoliotic deformity in a
minimally invasive method. The goal of this article is to present a comprehensive
review of the SHILLA system surgical technique and the associated literature
concerning this topic.
PMID- 27499649
TI - Fetal alcohol-spectrum disorders: identifying at-risk mothers.
AB - Fetal alcohol-spectrum disorders (FASDs) are a collection of physical and
neurobehavioral disabilities caused by prenatal exposure to alcohol. To prevent
or mitigate the costly effects of FASD, we must identify mothers at risk for
having a child with FASD, so that we may reach them with interventions.
Identifying mothers at risk is beneficial at all time points, whether prior to
pregnancy, during pregnancy, or following the birth of the child. In this review,
three approaches to identifying mothers at risk are explored: using
characteristics of the mother and her pregnancy, using laboratory biomarkers, and
using self-report assessment of alcohol-consumption risk. At present, all
approaches have serious limitations. Research is needed to improve the
sensitivity and specificity of biomarkers and screening instruments, and to link
them to outcomes as opposed to exposure. Universal self-report screening of all
women of childbearing potential should ideally be incorporated into routine
obstetric and gynecologic care, followed by brief interventions, including
education and personalized feedback for all who consume alcohol, and referral to
treatment as indicated. Effective biomarkers or combinations of biomarkers may be
used during pregnancy and at birth to determine maternal and fetal alcohol
exposure. The combination of self-report and biomarker screening may help
identify a greater proportion of women at risk for having a child with FASD,
allowing them to access information and treatment, and empowering them to make
decisions that benefit their children.
PMID- 27499652
TI - A novel implantable device for a minimally invasive surgical treatment of
obstructive sleep apnea: design and preclinical safety assessment.
AB - BACKGROUND: In obstructive sleep apnea (OSA), occlusion of the upper airway by
soft tissue causes intermittent hypoxemia and can have serious sequelae. A novel
implantable medical device for OSA is composed of a linear silicone elastic
element held in an extended state by a bioabsorbable external sheath. The implant
is delivered to the tongue base or soft palate via a minimally invasive approach.
Normal tissue healing anchors the device at the attachment points before the
bioabsorbable material dissolves and the elastic element contracts to stabilize
the surrounding tissue. METHODS: Device prototypes were evaluated in multiple
investigations: 1) a finite elements analysis model simulated the movement of the
tongue base during sleep with and without the implant; 2) dynamic mechanical
testing simulated 10 years' normal use; 3) cadaveric implantations were
conducted; 4) an ovine study in which implants of varying design were evaluated
via gross pathology and histological assessment; and 5) a canine study in which
implants of varying design in the tongue base and soft palate were evaluated via
gross pathology and histological assessment. RESULTS: 1) The implant was capable
of reducing ~95% of tongue base movement during simulated sleep; 2) implants
remained intact throughout the testing with no evidence of creep fatigue or
change in dynamic modulus; 3) the device could be reliably deployed in the
desired placement locations and was appropriate for various anatomies; and 4) all
implants were well tolerated through 1 year, with minimal inflammatory responses.
CONCLUSION: This new minimally invasive device for OSA has been demonstrated,
through various bench and animal testing, to be safe, well tolerated, suitable
for long-term use, and to function as intended. No adverse health consequences
were observed in the animals, and histological evaluation indicated good healing.
This study establishes proof of concept and supports human trials.
PMID- 27499654
TI - A Public Health Priority: Disparities in Gynecologic Cancer Research for African
Born Women in the United States.
AB - African-born immigrants comprise one of the fastest growing populations in the
U.S., nearly doubling its population size in recent years. However, it is also
one of the most underrepresented groups in health-care research, especially
research focused on gynecologic and breast malignancies. While the opportunity
exists for access to an advanced health-care system, as immigrants migrate to the
U.S., they encounter the same health-care inequalities that are faced by the
native-born population based on ethnicity and social class, potentiated by
limitations of health literacy and lack of familiarity with U.S. health systems.
Given the continued influx of African-born immigrants in the U.S., we sought to
understand the representation of this population in cervical and breast cancer
research, recognizing the population's high risk for these diseases at baseline
while residing in their native countries. We determined that there is limited
research in these diseases that disproportionately affect them; yet, there are
identifiable and potentially modifiable factors that contribute to this paucity
of evidence. This clinical commentary seeks to underscore the clear lack of
research available involving African-born immigrants with respect to gynecologic
and breast malignancies in the existing literature, demonstrate the need for more
robust research in this population, and provide fundamental insights into
barriers and solutions critical to the continued health of this growing
population.
PMID- 27499653
TI - Revisiting the mouse model of oxygen-induced retinopathy.
AB - Abnormal blood vessel growth in the retina is a hallmark of many retinal
diseases, such as retinopathy of prematurity (ROP), proliferative diabetic
retinopathy, and the wet form of age-related macular degeneration. In particular,
ROP has been an important health concern for physicians since the advent of
routine supplemental oxygen therapy for premature neonates more than 70 years
ago. Since then, researchers have explored several animal models to better
understand ROP and retinal vascular development. Of these models, the mouse model
of oxygen-induced retinopathy (OIR) has become the most widely used, and has
played a pivotal role in our understanding of retinal angiogenesis and ocular
immunology, as well as in the development of groundbreaking therapeutics such as
anti-vascular endothelial growth factor injections for wet age-related macular
degeneration. Numerous refinements to the model have been made since its
inception in the 1950s, and technological advancements have expanded the use of
the model across multiple scientific fields. In this review, we explore the
historical developments that have led to the mouse OIR model utilized today,
essential concepts of OIR, limitations of the model, and a representative
selection of key findings from OIR, with particular emphasis on current research
progress.
PMID- 27499655
TI - Use of microdoses for induction of buprenorphine treatment with overlapping full
opioid agonist use: the Bernese method.
AB - BACKGROUND: Buprenorphine is a partial u-opioid receptor agonist used for
maintenance treatment of opioid dependence. Because of the partial agonism and
high receptor affinity, it may precipitate withdrawal symptoms during induction
in persons on full u-opioid receptor agonists. Therefore, current guidelines and
drug labels recommend leaving a sufficient time period since the last full
agonist use, waiting for clear and objective withdrawal symptoms, and reducing
pre-existing full agonist therapies before administering buprenorphine. However,
even with these precautions, for many patients the induction of buprenorphine is
a difficult experience, due to withdrawal symptoms. Furthermore, tapering of the
full agonist bears the risk of relapse to illicit opioid use. CASES: We present
two cases of successful initiation of buprenorphine treatment with the Bernese
method, ie, gradual induction overlapping with full agonist use. The first
patient began buprenorphine with overlapping street heroin use after repeatedly
experiencing relapse, withdrawal, and trauma reactivation symptoms during
conventional induction. The second patient was maintained on high doses of
diacetylmorphine (ie, pharmaceutical heroin) and methadone during induction. Both
patients tolerated the induction procedure well and reported only mild withdrawal
symptoms. DISCUSSION: Overlapping induction of buprenorphine maintenance
treatment with full u-opioid receptor agonist use is feasible and may be
associated with better tolerability and acceptability in some patients compared
to the conventional method of induction.
PMID- 27499656
TI - Comparative Study on the Effects of Boiling, Steaming, Grilling, Microwaving and
Superheated Steaming on Quality Characteristics of Marinated Chicken Steak.
AB - The effects of five different cooking methods (boiling, steaming, grilling,
microwaving, and superheated steaming) on proximate composition, pH, color,
cooking loss, textural properties, and sensory characteristics of chicken steak
were studied. Moisture content and lightness value (L*-value) were higher in
superheated steam cooked chicken steak than that of the other cooking treatments
such as boiling, steaming, grilling and microwaving cooking (p<0.05), whereas
protein content, redness value (a*-value), hardness, gumminess, and chewiness of
superheated steam cooked chicken steak was lower than that in the other cooking
treatments (p<0.05). Fat content and ash content, springiness, and cohesiveness
were not significantly different among the chicken steak cooked using various
methods (p>0.05). Among the sensory characteristics, tenderness score, juiciness
score and overall acceptability score were the highest for the superheated steam
samples (p<0.05), whereas no difference in flavor scores were observed among the
other treatments (p>0.05). These results show that marinated chicken steak
treated with superheated steam in a preheated 250C oven and 380C steam for 5 min
until core temperature reached 75C improved the quality characteristics and
sensory properties the best. Therefore, superheated steam was useful to improve
cooked chicken steak.
PMID- 27499657
TI - Effects of Soy Protein Hydrolysates Prepared by Varying Subcritical Media on the
Physicochemical Properties of Pork Patties.
AB - This study investigated the effect of soy protein hydrolysates (SPH) prepared by
varying subcritical media on the physicochemical properties of pork patties. For
resource of SPH, two different soybean species (Glycine max Merr.) of Daewonkong
(DWK) and Saedanbaek (SDB) were selected. SPH was prepared by subcritical
processing at 190C and 25 MPa under three different of media (water, 20% ethanol
and 50% ethanol). Solubility and free amino group content revealed that water was
better to yield larger amount of SPH than ethanol/water mixtures, regardless of
species. Molecular weight (Mw) distribution of SPH was also similar between two
species, while slightly different Mw distribution was obtained by subcritical
media. For pork patty application, 50% ethanol treatment showed clear red color
comparing to control after 14 d of storage. In addition, ethanol treatment had
better oxidative stability than control and water treatment based on
thiobarbituric acid-reactive substances (TBARS) analysis. For eating quality,
although 20% ethanol treatment in SDB showed slightly higher cooking loss than
control, generally addition of SPH did not affect the water-binding properties
and hardness of pork patties. Consequently, the present study indicated that 50%
ethanol was the best subcritical media to produce SPH possessing antioxidant
activity, and the SPH produced from DWK exhibited better antioxidant activity
than that produced SDB.
PMID- 27499658
TI - Induction of Oral Tolerance by Gamma-Irradiated Ovalbumin Administration.
AB - Oral administration of soluble antigen can induce peripheral tolerance to the
antigen. This study was conducted to evaluate whether gamma-irradiated ovalbumin
(OVA) can induce oral tolerance. To investigate this, we administrated intact or
irradiated OVA to mice, induced allergic response using intact OVA and alum, then
compared humoral and cellular immune responses. Mice treated with gammairradiated
OVA had less OVA-specific IgE compared with those who were administered intact
OVA. There was no difference in levels of OVA-specific IgG+A+M, IgG1, and IgG2a.
Splenocytes of mice administered irradiated OVA showed similar OVA-specific T
cell proliferation and secretion of IFN-gamma and IL-4. However, there was an
increase in IL-2 and a decrease of IL-6 secretion in mice treated with irradiated
OVA. These results indicate that gamma-irradiated OVA have similar effects to
intact OVA on antigen tolerance.
PMID- 27499659
TI - Sensory Property Improvement of Jokbal (Korean Pettitoes) Made from Frozen Pig
Feet by Addition of Herbal Mixture.
AB - This study was conducted to improve sensory quality of Jokbal (Korean Pettitoes)
made from frozen pig feet by addition of herbal mixture (glasswort, raspberry and
Sansa powders). After adding herbal mixture, lipid oxidation (2-thiobarbituric
acid values, TBARS), sensory property, and textural property were determined.
Herbs were individually added into cooking soup at concentration of 6% (low
concentration treatment, LCT) or 12% (high concentration treatment, HCT) of raw
pig feet. Refrigerated pig feet were used as control. Thawed feet without any
herbal mixture were used as freezing treatment (FT). TBARS in LCT or HCT were
lower than that in FT, and showed the similar to that in Control. Addition of the
herbal mixture was effective in improving the flavor and textural property of
thawed feet by inhibiting lipid oxidation and protein denaturation in a dose
dependent manner.
PMID- 27499660
TI - Impact of Cooking, Storage, and Reheating Conditions on the Formation of
Cholesterol Oxidation Products in Pork Loin.
AB - This study investigates the effect of cooking, storage, and reheating conditions
on the formation of cholesterol oxidation products (COPs) in pork loin. Samples
of pork loin procured 24 h postmortem were initially processed and assessed for
total fat and cholesterol content. The cooking methods evaluated were pan
roasting, steaming, oven grilling, and microwaving. Cooked pork loin samples were
stored at 4C and reheated after 3 and 6 d of storage using the original method of
preparation or alternately, microwaving. Fat content increased significantly with
cooking as a result of the loss in moisture but cholesterol content remained
unchanged. Pan roasting and microwave cooking caused a significantly higher
production of COPs, as with the process of reheating using microwave, pan
roasting, and oven grilling methods. The major COPs found in pork loin were
cholestanetriol, 20-hydroxycholesterol, and 25-hydroxycholesterol, whose
concentrations varied according to the different cooking and reheating methods
used. Moreover, the aerobic storage of cooked pork loin under a refrigerated
condition also increased the formation of cholesterol oxides on reheating.
PMID- 27499661
TI - Pork Quality Traits According to Postmortem pH and Temperature in Berkshire.
AB - This study was performed to investigate the role of pH and temperature
postmortem, and to demonstrate the importance of these factors in determining
meat quality. Postmortem pH 45min (pH at 45 min postmortem or initial pH) via
analysis of Pearson's correlation showed high positive correlation with pH change
pH c24 (pH change from pH 45min to pH 24h postmortem). However, postmortem pH
after 24 h (pH 24h or ultimate pH) had a high negative correlation with pH
change, pH c24 , CIE L*, and protein content. Initial temperature postmortem (T
1h ) was positively associated with a change in temperature from 45 min to 24 h
postmortem (T c24 ) and cooking loss, but negatively correlated with water
holding capacity. Temperature at 24 h postmortem (T 24h ) was negatively
associated with T c24 . Collectively, these results indicate that higher initial
pH was associated with higher pH c24 , T 1h , and T c24 . However, higher initial
pH was associated with a reduction in carcass weight, backfat thickness, CIE a*
and b*, water holding capacity, collagen and fat content, drip loss, and cooking
loss as well as decreased shear force. In contrast, CIE a* and b*, drip loss,
cooking loss, and shear force in higher ultimate pH was showed by a similar
pattern to higher initial pH, whereas pH c24 , carcass weight, backfat thickness,
water holding capacity, fat content, moisture content, protein content, T 1h , T
24h , and T c24 were exhibited by completely differential patterns (p<0.05).
Therefore, we suggest that initial pH, ultimate pH, and temperatures postmortem
are important factors in determining the meat quality of pork.
PMID- 27499662
TI - Screening of Cholesterol-lowering Bifidobacterium from Guizhou Xiang Pigs, and
Evaluation of Its Tolerance to Oxygen, Acid, and Bile.
AB - Cardiovascular and cerebrovascular diseases seriously harm human health, and
Bifidobacterium is the most beneficial probiotic in the gastrointestinal tract of
humans. This work aimed to screen cholesterol-lowering Bifidobacterium from
Guizhou Xiang Pig and evaluate its tolerance to oxygen, acid, and bile. Twenty
seven aerotolerant strains with similar colony to Bifidobacterium were isolated
through incubation at 37C in 20% (v/v) CO2-80% (v/v) atmospheric air by using
Mupirocin lithium modified MRS agar medium, modified PTYG with added CaCO3, and
modified PTYG supplemented with X-gal. Ten strains with cholesterol-lowering
rates above 20% (w/w) were used for further screening. The selected strains'
tolerance to acid and bile was then determined. A combination of colony and cell
morphology, physiological, and biochemical experiments, as well as 16S rRNA gene
sequence analysis, was performed. Results suggested that BZ25 with excellent
characteristics of high cholesterol-removal rate of 36.32% (w/w), as well as
tolerance to acid and bile, was identified as Bifidobacterium animalis subsp.
lactis. To further evaluate Bifidobacterium BZ25's growth characteristic and
tolerance to oxygen, culture experiments were performed in liquid medium and an
agar plate. Findings suggested that BZ25 grew well both in environmental 20%
(v/v) CO2-80% (v/v) atmospheric air and in 100% atmospheric air because BZ25
reached an absorbance of 1.185 at 600 nm in 100% atmospheric air. Moreover, BZ25
was aerotolerant and can grow in an agar medium under the environmental condition
of 100% atmospheric air. This study can lay a preliminary foundation for the
potential industrial applications of BZ25.
PMID- 27499663
TI - Correlation between Antioxidant Enzyme Activity, Free Iron Content and Lipid
Oxidation in Four Lines of Korean Native Chicken Meat.
AB - This study was conducted to observe the association between antioxidant enzyme
activity, free iron content and lipid oxidation of Korean native chicken (KNC)
meat during refrigerated storage. Four lines of KNC (Yeonsan ogye, Hyunin black,
Hoengseong yakdak and Hwangbong) were raised under similar conditions. A total of
16 roosters were randomly sampled and slaughtered at the age of 12 mon. The
breast and thigh meats were stored aerobically for 10 d at 4C. Although thigh
meat had higher antioxidant enzyme activity, it was more susceptible to lipid
oxidation and released more iron during storage than breast meat. Aerobic
refrigerated storage for 10 d significantly decreased the activity of antioxidant
enzymes and increased the amount of free iron and malondialdehyde. The activities
of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were negatively
correlated with lipid oxidation, whereas that of catalase was not. The amount of
free iron was positively associated with lipid oxidation. We concluded that
chicken line did not affect strongly on antioxidant enzyme activity and lipid
oxidation in breast meat of KNC. However, the thigh meat of Hwangbong and Hyunin
black had higher SOD and GSH-Px activity, respectively, and lower malondialdehyde
contents than that of other chickens. SOD, GSH-Px and free iron play significant
roles in meat lipid oxidation during refrigerated storage.
PMID- 27499664
TI - Effects of Drying Temperature on Antioxidant Activities of Tomato Powder and
Storage Stability of Pork Patties.
AB - This study was performed to evaluate the antioxidant activity of oven-dried
tomato powder (OTP) as affected by drying temperature and the effect of OTP on
the product quality of pork patties. Three OTP products were obtained by drying
of fresh tomato at 60, 80 and 100C oven until constant weight was obtained. Total
phenolic content of three kinds of OTPs ranged from 1.95 to 5.94 g/100 g. The
highest amount of total phenolic compound was observed in OTP dried at 100C.
Antioxidant activity of three kinds of OTPs was measured by 1,1-diphenyl-2
pycrylhydrazyl (DPPH)-radical scavenging activity, iron chelating ability,
reducing power and measurement of lipid peroxide in linoleic acid emulsion
system. In all parameters, OTP at 100C showed the higher antioxidant activity
than other temperatures (p<0.05). Based on the model study, the physicochemical
properties, and antioxidant and antimicrobial activities of pork patties
containing 1% OTP were measured. Redness of pork patties were increased with the
addition of OTPs (p<0.05). Thiobarbituric acid reactive substances (TBARS) values
of raw pork patties containing OTPs were lower than those of control (CTL) until
7 d of storage, regardless of drying temperatures (p<0.05). Peroxide values of
pork patties made with OTP (1%) were lower than those of CTL until the end of
storage time (p<0.05). However, no antimicrobial activities were observed among
the treatments (p>0.05). Therefore, OTPs could be used as a natural antioxidant
in meat products.
PMID- 27499665
TI - Effects of Mixed Bone and Brisket Meat on Physico-Chemical Characteristics of
Shank Bone and Rib Extracts from Hanwoo.
AB - This study was conducted to investigate the effects of mixed bone and brisket
meat on the quality characteristics and nutritional components of shank bone
extract and rib extract from Hanwoo. The pH values were influenced by the raw
bones, mixed bone, brisket meat and their interactions (p<0.05). The salinity,
sugar content, turbidity, and essential amino acid values increased significantly
with addition of mixed bone and brisket meat. All attributes of sensory
evaluation score were the highest in T6 (Rib 500 g + Mixed bone 500 g + Brisket
meat 400 g) (p<0.05). The mixed bone significantly increased the saturated fatty
acids of shank bone extract (p<0.001). Thus, the addition of mixed bone and
brisket meat had a positive effect on the quality and nutritional components in
shank and rib extracts of Hanwoo cattle.
PMID- 27499666
TI - Effect of Aging Time on Physicochemical Meat Quality and Sensory Property of
Hanwoo Bull Beef.
AB - This study was conducted to investigate the meat quality and sensory properties
of 12 major cuts from 10 Hanwoo bulls (25-32 mon of age) after they were aged at
2C for 0, 7, 14, and 21 d. Protein content (%) was between 19.17 and 22.50%.
Intramuscular fat content ranged from 2.79 to 8.39%. The collagen content of the
chuck roll, chuck tender, and short plate muscles was higher (1.97-2.04%) than
that of the striploin muscles (1.48%) (p<0.05). CIE lightness (L*) values
increased with an increase in aging days for tenderloin, loin, chuck roll, oyster
blade, short plate, top sirloin, and eye of round muscles (p<0.05). Most muscles,
except the short plate, showed no significant changes in redness CIE (a*) and
yellowness (b*) color values during aging. The tenderloin, loin, and striploin
showed significantly higher water holding capacity (58.60-62.06%) than that of
chuck roll and short plate (53.86-57.07%) muscles (p<0.05). The Warner-Bratzler
shear force values of most muscles decreased significantly as the aging period
increased (p<0.05), exception the tenderloin. The chuck tender muscles showed the
highest cooking loss, whereas tenderloin muscle showed the lowest (p<0.05). The
tenderloin muscle had the longest sarcomere length (SL) (3.67-3.86 MUm) and the
bottom round muscle had the shortest SL (2.21-2.35 MUm) (p<0.05). In the sensory
evaluation, tenderness and overall-likeness scores of most muscles increased with
increase in aging days. The tenderloin and oyster blade showed relatively higher
tenderness and overall-likeness values than did the other muscles during the
aging period. No significant differences were noted in juiciness and flavor
likeness scores among muscles and aging days.
PMID- 27499667
TI - Anti-obesity Effect of Yogurt Fermented by Lactobacillus plantarum Q180 in Diet
induced Obese Rats.
AB - This study aimed to investigate the anti-obesity effects of yogurt fermented by
Lactobacillus plantarum Q180 in diet-induced obese rats. To examine the effects,
male Sprague-Dawley rats were fed on six different diets, as follows: Group A was
fed an ND and orally administrated saline solution; Group B, an HFD and orally
administrated saline solution; Group C, an HFD and orally administrated yogurt
fermented by ABT-3 and L. plantarum Q180; Group D, an HFD and orally
administrated yogurt with added Garcinia cambogia extract, fermented by ABT-3 and
L. plantarum Q180; Group E, an HFD and orally administrated yogurt fermented by
L. plantarum Q180; and Group F, an HFD and orally administrated yogurt with added
Garcinia cambogia extract, fermented by L. plantarum Q180 for eight weeks. After
eight weeks, the rate of increase in bodyweight was 5.14%, 6.5%, 3.35% and 10.81%
lower in groups C, D, E and F, respectively, compared with group B; the
epididymal fat weight of groups E and F was significantly lower than that of
group B; and the level of triglyceride and leptin was significantly reduced in
groups C, D, E and F compared to group B. In addition, the level of AST was
reduced in group C compared to the other groups. To examine the effects of yogurt
on the reduction of adipocyte size, the adipocyte sizes were measured. The number
of large-size adipose tissue was less distributed in groups A, C, D, E and F than
in group B.
PMID- 27499668
TI - Comparison of Carcass and Meat Quality Traits among Three Rabbit Breeds.
AB - The objective of this study was to compare carcass composition and meat quality
traits in the longissimus dorsi and biceps femoris muscles in the Hyla, Champagne
and Tianfu Black rabbit breeds. Tianfu Black rabbits had the heaviest head, skin,
thoracic viscera and commercial carcass percentage (p<0.05). In addition, Tianfu
Black had the highest pH0 h value, followed by the Champagne and Hyla breeds
(p<0.01) in the longissimus dorsi and biceps femoris muscles. Tianfu Black had a
higher a* (0 h and 24 h) than the other two breeds in both longissimus dorsi and
biceps femoris muscles (p<0.05). The Hyla, Champagne, and Tianfu Black breeds
showed a similar pattern of differences for meat quality traits (pH, L*, a* and
b*) measured in fresh meat (0 h) and meat stored for 24 h. Hyla had the highest
IMF values of the three breeds (p<0.01). The lower intramuscular fat of Tianfu
Black and Champagne rabbits gives them an advantage over Hyla rabbits among most
consumers seeking lean rabbit meat.
PMID- 27499669
TI - Enhanced Microbial, Functional and Sensory Properties of Herbal Yogurt Fermented
with Korean Traditional Plant Extracts.
AB - This study evaluated the effects of two Korean traditional plant extracts
(Diospyros kaki THUNB. leaf; DK, and Nelumbo nucifera leaf; NN) on the
fermentation, functional and sensory properties of herbal yogurts. Compared to
control fermentation, all plant extracts increased acidification rate and reduced
the time to complete fermentation (pH 4.5). Supplementation of plant extracts and
storage time were found to influence the characteristics of the yogurts,
contributing to increased viability of starter culture and phenolic compounds. In
particular, the increase in the counts of Streptococcus thermophilus and
Lactobacillus delbrueckii subsp. bulgaricus was highest (2.95 and 1.14 Log CFU/mL
respectively) in DK yogurt. Furthermore, supplementation of the plant extracts
significantly influenced to increase the antioxidant activity and water holding
capacity and to produce volatile compounds. The higher antioxidant activity and
water holding capacity were observed in NN yogurt than DK yogurt. Moreover, all
of the sensory characteristics were altered by the addition of plant extracts.
Addition of plant extracts increased the scores related to flavor, taste, and
texture from plain yogurt without a plant extract, as a result of volatile
compounds analysis. Thus, the overall preference was increased by plant extracts.
Consequently, supplementation of DK and NN extracts in yogurt enhanced the
antioxidant activity and physical property, moreover increased the acceptability
of yogurt. These findings demonstrate the possibility of using plant extracts as
a functional ingredient in the manufacture of herbal yogurt.
PMID- 27499671
TI - Determination of Energy and Nutrient Utilization of Enzyme-treated Rump Round
Meat and Lotus Root Designed for Senior People with Young and Age d Hens as an
Animal Model.
AB - This study aimed to examine the nutrient utilization of rump round meat and lotus
root using young (32 wk) and aged hens (108 wk) as an animal model. Rump round
meat and lotus root were prepared with or without enzymatic treatment. For each
age group of laying hens, a total of 24 Hy-Line Brown laying hens were randomly
allotted to one of two dietary treatments with six replicates. For rump round
meat, the true total tract retention rate (TTTR) of dry matter (DM) and nitrogen
(N) were unaffected by either enzymatic treatment or hen age. However, aged hens
had greater (p<0.01) TTTR of energy and crude fat than young hens. Enzymatic
treatment did not influence the TTTR of energy or crude fat. In addition, we did
not observe any significant interaction between the TTTR of DM, energy, N, or
crude fat in rump round meat and hen age or enzymatic treatment. The TTTR of DM
remained unchanged between controls and enzyme-treated lotus root for young hens.
However, enzyme-treated lotus root exhibited greater (p<0.05) TTTR of DM than
control lotus root for aged hens, resulting in a significant interaction
(p<0.05). The TTTR of energy and N in lotus roots were greater (p<0.01) for aged
hens than for young hens. In conclusion, enzymatic treatment exerted beneficial
effects on energy and nutrient utilization in aged hens, suggesting the aged hen
model is practical for simulation of metabolism of elderly individuals.
PMID- 27499670
TI - Inactivation of Salmonella on Eggshells by Chlorine Dioxide Gas.
AB - Microbiological contamination of eggs should be prevented in the poultry
industry, as poultry is one of the major reservoirs of human Salmonella. ClO2 gas
has been reported to be an effective disinfectant in various industry fields,
particularly the food industry. The aims of this study were to evaluate the
antimicrobial effect of chlorine dioxide gas on two strains of Salmonella
inoculated onto eggshells under various experimental conditions including
concentrations, contact time, humidity, and percentage organic matter. As a
result, it was shown that chlorine dioxide gas under wet conditions was more
effective in inactivating Salmonella Enteritidis and Salmonella Gallinarum
compared to that under dry conditions independently of the presence of organic
matter (yeast extract). Under wet conditions, a greater than 4 log reduction in
bacterial populations was achieved after 30 min of exposure to ClO2 each at 20
ppm, 40 ppm, and 80 ppm against S. Enteritidis; 40 ppm and 80 ppm against S.
Gallinarum. These results suggest that chlorine dioxide gas is an effective agent
for controlling Salmonella, the most prevalent contaminant in the egg industry.
PMID- 27499672
TI - Effects on the Qualities of Proteolysis to Beef by Non-coating and Coating
Protease Treatment.
AB - This study was performed to improve the techniques used for tenderizing red meat
as elderly food. Beef meat was immersed in liposome encapsulated enzyme solution
and the effect of protease encapsulation on the beef properties was analyzed. The
protease encapsulation properties were analyzed according to the size
distribution and enzymatic activity. After enzyme reaction on the beef, the
chemical properties of the meat such as pH, water holding capacity, shear rate,
lipid oxidation and total volatile basic nitrogen (TVB-N) were analyzed. The pH
of the beef increased during the reaction and coating protease (CP) was higher
than non-coating protease (NCP). Total color differences were increased
remarkably after 36 h and generally, the difference in CP was relatively lower
than in NCP. WHC was significantly decreased within 24 h, and no effect from the
protease coating was observed. Protease activity was significantly increased
within 48 h and no differences in the enzyme coating were observed. The TVB-N
value of NCP was increased within 24 h while CP was sustained for up to 36 h. The
TVB-N value of protease treated meat increased after 36 h and no effect from the
protease coating was detected. Consequently, liposome encapsulated protease was
found to have similar properties as non-coated protease. Application of liposome
seems to be an interesting option for injecting various functional materials
without changing the properties of meat.
PMID- 27499673
TI - Evaluation of Mixed Probiotic Starter Cultures Isolated from Kimchi on
Physicochemical and Functional Properties, and Volatile Compounds of Fermented
Hams.
AB - The objective of this study was to investigate the effects of mixed starter
cultures isolated from kimchi on physicochemical properties, functionality and
flavors of fermented ham. Physicochemical properties, microbial counts, shear
force, cholesterol contents and volatile compounds of fermented ham were
investigated during processing (curing and ripening time). Curing process for 7 d
increased saltiness, however, decreased hunter color values (L, a, and b values).
Ripening process for 21 d increased most parameters, such as saltiness, color
values, weight loss, shear force and cholesterol content due to the drying
process. The mixed starter culture had higher lactic acid bacteria than the
commercial one. While eight volatile compounds were identified from fermented
hams during curing process, total fiftyeight volatile compounds were identified
from fermented hams during ripening process. The main volatile compounds were
alcohols, esters and furans. However, no differences in volatile compounds were
observed between two batches. Fermented hams (batch B) manufactured with
probiotic starter culture (LPP) had higher sensory score in texture, color and
overall acceptability than counterparts (batch A), while the opposite trend was
observed in flavor. Therefore, mixed probiotic starter culture isolated from
kimchi might be used as a starter culture to be able to replace with commercial
starter culture (LK-30 plus) for the manufacture of fermented ham.
PMID- 27499674
TI - Effect of Chicory Fiber and Smoking on Quality Characteristics of Restructured
Sausages.
AB - This study was conducted to investigate the effects of chicory fiber for the
replacement of fat and smoking on quality characteristics of restructured
sausages. Treatments were as follows; CONTROL: Pork backfat 20%, T1: Pork backfat
10% + Chicory fiber 10%, T2: CONTROL + Smoking, T3: T1 + Smoking. The addition of
chicory fiber significantly reduced the moisture, fat, hardness and pH values,
whereas the smoking treatment increased the fat, redness and pH values of
restructured sausages (p<0.01). Additionally, interaction of them significantly
affected the ash, chewiness and hardness values of restructured sausages. As a
result, although the addition of chicory fiber decreased the quality
characteristics of sausage, smoking treatment improved the reduced quality.
Therefore, the chicory fiber and smoking treatment is helpful to develop
restructured sausage products with reduced fat and compensated quality.
PMID- 27499675
TI - Taphonomy and diversity of Middle Miocene decapod crustaceans from the Novohrad
Nograd Basin, Slovakia, with remarks on palaeobiography.
AB - Decapod crustacean assemblages from the Middle Miocene (lower
'Badenian'=Langhian) volcanoclastic Plastovce Beds (Sebechleby Formation) in the
Slovakian part of the Novohrad-Nograd Basin comprise five species in five
families (Callianassidae, Laomediidae, Munididae, Cancridae and Retroplumidae)
and are dominated by the cancrid crab Tasadia carniolica (Bittner, 1884). Munida
sp. constitutes the first record of this genus from Slovakia and the second from
the European Neogene. Burrowing shrimp (Jaxea kuemeli Bachmayer, 1954) are
associated with burrows tentatively attributed to this species. The occurrence of
Retropluma slovenica Gasparic & Hyzny, 2014, previously recorded from the Lower
Miocene of Slovenia, extends both the geographical distribution and
stratigraphical range of the species. Differential decapod diversity at four
localities in the Plastovce area can be explained by collecting bias and
palaeoenvironmental factors. The palaeosetting is interpreted as a muddy-bottom,
nearshore zone with a water depth of approximately 100 m. Abundant articulated
crabs suggest rapid burial. Third maxillipeds in open posture in some specimens
may indicate respiratory stress of the animals, suggesting episodic events of
rapid volcanoclastic flows responsible for killing crabs and promoting their
preservation. Species composition of the decapod fauna of the Plastovce Beds
further strengthens similarities with Miocene faunas from the North Sea Basin.
PMID- 27499676
TI - Health activism and the logic of connective action. A case study of rare disease
patient organisations.
AB - This exploratory work investigates the role of digital media in expanding health
discourse practices in a way to transform traditional structures of agency in
public health. By focusing on a sample of rare disease patient organisations as
representative of contemporary health activism, this study investigates the role
of digital communication in the development of (1) bottom-up sharing and co
production of health knowledge, (2) health public engagement dynamics and (3)
health information pathways. Findings show that digital media affordances for
patient organisations go beyond the provision of social support for patient
communities; they ease one-way, two-way and crowdsourced processes of health
knowledge sharing, exchange and co-production, provide personalised routes to
health public engagement and bolster the emergence of varied pathways to health
information where experiential knowledge and medical authority are equally
valued. These forms of organisationally enabled connective action can help the
surfacing of personal narratives that strengthen patient communities, the bottom
up production of health knowledge relevant to a wider public and the development
of an informational and eventually cultural context that eases patients'
political action.
PMID- 27499677
TI - Accounting for failure: risk-based regulation and the problems of ensuring
healthcare quality in the NHS.
AB - In this paper, we examine why risk-based policy instruments have failed to
improve the proportionality, effectiveness, and legitimacy of healthcare quality
regulation in the National Health Service (NHS) in England. Rather than trying to
prevent all possible harms, risk-based approaches promise to rationalise and
manage the inevitable limits of what regulation can hope to achieve by focusing
regulatory standard-setting and enforcement activity on the highest priority
risks, as determined through formal assessments of their probability and
consequences. As such, risk-based approaches have been enthusiastically adopted
by healthcare quality regulators over the last decade. However, by drawing on
historical policy analysis and in-depth interviews with 15 high-level UK
informants in 2013-2015, we identify a series of practical problems in using risk
based policy instruments for defining, assessing, and ensuring compliance with
healthcare quality standards. Based on our analysis, we go on to consider why,
despite a succession of failures, healthcare regulators remain committed to
developing and using risk-based approaches. We conclude by identifying several
preconditions for successful risk-based regulation: goals must be clear and trade
offs between them amenable to agreement; regulators must be able to reliably
assess the probability and consequences of adverse outcomes; regulators must have
a range of enforcement tools that can be deployed in proportion to risk; and
there must be political tolerance for adverse outcomes.
PMID- 27499678
TI - Enhancement of Plant Productivity in the Post-Genomics Era.
AB - Obtaining high plant yield is not always achievable in agricultural activity as
it is determined by various factors, including cultivar quality, nutrient and
water supplies, degree of infection by pathogens, natural calamities and soil
conditions, which affect plant growth and development. More noticeably,
sustainable plant productivity to provide sufficient food for the increasing
human population has become a thorny issue to scientists in the era of
unpredictable global climatic changes, appearance of more tremendous or multiple
stresses, and land restriction for cultivation. Well-established agricultural
management by agrotechnological means has shown no longer to be effective enough
to confront with this challenge. Instead, in order to maximize the production, it
is advisable to implement such practices in combination with biological
applications. Nowadays, high technologies are widely adopted into agricultural
production, biological diversity conservation and crop improvement. Wang et al.
has nicely outlined the utilization of DNA-based technologies in this field.
Among these are the applications of (i) DNA markers into cultivar identification,
seed purity analysis, germplasm resource evaluation, heterosis prediction,
genetic mapping, cloning and breeding; and (ii) gene expression data in
supporting the description of crop phenology, the analytic comparison of crop
growth under stress versus non-stress conditions, or the study of fertilizer
effects. Besides, various purposes of using transgenic technologies in
agriculture, such as generating cultivars with better product quality, better
tolerance to biotic or abiotic stress, are also discussed in the review. One of
the important highlights in this issue is the review of the benefits brought by
high-throughput sequencing technology, which is also known as next-generation
sequencing (NGS). It is not so difficult to recognize that its application has
allowed us to carry out biological studies at much deeper level and larger scale.
In their article, Onda and Mochida detailed how to use these technologies in
fully characterizing the genetic diversity or multigenecity within a particular
plant species. The authors discussed the constant innovation of sequencing
platforms which has made sequencing technologies become more superior and more
powerful than ever before. Additionally, the efforts result in not only further
cut down of the sequencing cost and increase in the sequencing speed, but also
improvement in sequencing accuracy and extended sequencing application to studies
at both DNA and RNA levels. Such knowledge will help the scientists interpret, at
least partially, how plants can adapt to various environmental conditions, or how
different cultivars can respond differently to the same stress. Another article
by Ong et al. also laid emphasis on the importance of various high-throughput
sequencing platforms, thanks to which a large number of genomic databases
supplied with detailed annotation and useful bioinformatics tools have been
established to assist geneticists. Readers can find in this review the summary of
available plant-specific genomic databases up-to-date and popular web-based
resources that are relevant for comparative genomics, plant evolution and
phylogenomics studies. These, along with other approaches, such as quantitative
trait locus and genome-wide association study, will lay foundation for prediction
and identification of genes or alleles responsible for valuable agronomic traits,
contributing to the enhancement of plant productivity by genetic engineering
approach. In this thematic issue, specific examples for crop improvement are also
demonstrated. The first showcase is given by Nongpiur et al. who provided
evidence that synergistic employment of genomics approaches and high-throughput
gene expression methods have aided in dissecting the salinity-responsive
signaling pathway, identifying genes involved in the stress response and
selecting candidate genes for further characterization aimed at generating new
cultivars with better salinity stress tolerance. This paper is also a good
reference source for readers who wish to get an overview about the general
process from gene prediction to validation by experiments, including the details
on techniques and approaches used. Another demonstration is provided by Khan et
al. whose interest is enhancement of drought tolerance in crops. The focus of
this article is to overview our current understanding of mechanisms regulating
plants responses to drought. Evaluation of plant performance to drought and
production of new elite varieties with better drought tolerance on the basis of
using phenotyping and genomics-assisted breeding are also well discussed. In
addition to the topics of environmental stress tolerance in plants, current
knowledge on improving biotic stress tolerance is also summarized in our issue.
Current picture on crosstalk of signaling mechanisms in rice between its immune
system and symbiosis with microorganisms is presented by Akamatsu et al. Rice
responses to bacteria and fungi via interactions between the plant pattern
recognition receptors and the molecular microbe-associated molecular patterns are
described in detail and suggested as targets for manipulation in order to
increase disease resistance in crops. On the other hand, Bouain et al. are
concerned about nutrient deficiency; specifically, how plant root system develops
under growing conditions with inadequate phosphate. The authors overviewed our
current understanding of the low phosphate-responsive mechanisms in Arabidopsis
model plant, which was gained by using a combination of various advanced methods,
including high-througput phenotyping, system biology analysis and "omics"
technologies. Stress management in plants is proposed to be also achievable by
regulating activities of cyclic nucleotide-gated ion channels. As emphasized in
the paper of Jha et al., the application of such channels is important in
mediating cellular ion homeostasis and plant tolerance to both biotic and abiotic
stresses. In summary, with recent progresses in biological and biotechnological
areas, especially rapid development of advanced technologies in biological system
modeling, functional genomics, computer-based analyzing tools, genetic
engineering and molecular breeding, biological control and biotechnological
applications in agriculture have brought about an extraordinary revolution and
have been considered the most powerful approaches in maintaining or even
increasing crop yield. Therefore, in this issue, we would like to introduce to
the audience a collection of various strategies used for enhancing crop
productivity, with the focus on advanced biological-biotechnological platforms in
the post-genomics era.
PMID- 27499679
TI - Crosstalk of Signaling Mechanisms Involved in Host Defense and Symbiosis Against
Microorganisms in Rice.
AB - Rice is one of the most important food crops, feeding about half population in
the world. Rice pathogens cause enormous damage to rice production worldwide. In
plant immunity research, considerable progress has recently been made in our
understanding of the molecular mechanisms underlying microbe-associated molecular
pattern (MAMP)-triggered immunity. Using genome sequencing and molecular
techniques, a number of new MAMPs and their receptors have been identified in the
past two decades. Notably, the mechanisms for chitin perception via the lysine
motif (LysM) domain-containing receptor OsCERK1, as well as the mechanisms for
bacterial MAMP (e.g. flg22, elf18) perception via the leucine-rich repeat (LRR)
domain-containing receptors FLS2 and EFR, have been clarified in rice and
Arabidopsis, respectively. In chitin signaling in rice, two direct substrates of
OsCERK1, Rac/ROP GTPase guanine nucleotide exchange factor OsRacGEF1 and receptor
like cytoplasmic kinase OsRLCK185, have been identified as components of the
OsCERK1 complex and are rapidly phosphorylated by OsCERK1 in response to chitin.
Interestingly, OsCERK1 also participates in symbiosis with arbuscular mycorrhizal
fungi (AMF) in rice and plays a role in the recognition of short-chitin molecules
(CO4/5), which are symbiotic signatures included in AMF germinated spore exudates
and induced by synthetic strigolactone. Thus, OsCERK1 contributes to both
immunity and symbiotic responses. In this review, we describe recent studies on
pathways involved in rice immunity and symbiotic signaling triggered by
interactions with microorganisms. In addition, we describe recent advances in
genetic engineering by using plant immune receptors and symbiotic microorganisms
to enhance disease resistance of rice.
PMID- 27499680
TI - Recent Advances in Understanding the Molecular Mechanisms Regulating the Root
System Response to Phosphate Deficiency in Arabidopsis.
AB - Phosphorus (P) is an essential macronutrient for plant growth and development.
Inorganic phosphate (Pi) is the major form of P taken up from the soil by plant
roots. It is well established that under Pi deficiency condition, plant roots
undergo striking morphological changes; mainly a reduction in primary root length
while increase in lateral root length as well as root hair length and density.
This typical phenotypic change reflects complex interactions with other nutrients
such as iron, and involves the activity of a large spectrum of plant hormones.
Although, several key proteins involved in the regulation of root growth under Pi
deficiency have been identified in Arabidopsis, how plants adapt roots system
architecture in response to Pi availability remains an open question. In the
current post-genomic era, state of the art technologies like high-throughput
phenotyping and sequencing platforms,"omics" methods, together with the
widespread use of system biology and genome-wide association studies will help to
elucidate the genetic architectures of root growth on different Pi regimes. It is
clear that the large-scale characterization of molecular systems will improve our
understanding of nutrient stress phenotype and biology. Herein, we summarize the
recent advances and future directions towards a better understanding of
Arabidopsis root developmental programs functional under Pi deficiency. Such a
progress is necessary to devise strategies to improve the Pi use efficiency in
plants that is an important issue for agriculture.
PMID- 27499681
TI - Role of Cyclic Nucleotide Gated Channels in Stress Management in Plants.
AB - Tolerance of plants to a number of biotic and abiotic stresses such as pathogen
and herbivore attack, drought, salinity, cold and nutritional limitations is
ensued by complex multimodule signaling pathways. The outcome of this complex
signaling pathways results in adaptive responses by restoring the cellular
homeostasis and thus promoting survival. Functions of many plant cation
transporter and channel protein families such as glutamate receptor homologs
(GLRs), cyclic nucleotide-gated ion channel (CNGC) have been implicated in
providing biotic and abiotic stress tolerance. Ion homeostasis regulated by
several transporters and channels is one of the crucial parameters for the
optimal growth, development and survival of all living organisms. The CNGC family
members are known to be involved in the uptake of cations such as Na(+), K(+) and
Ca(2+) and regulate plant growth and development. Detail functional genomics
approaches have given an emerging picture of CNGCs wherein these protein are
believed to play crucial role in pathways related to cellular ion homeostasis,
development and as a 'guard' in defense against biotic and abiotic challenges.
Here, we discuss the current knowledge of role of CNGCs in mediating stress
management and how they aid plants in survival under adverse conditions.
PMID- 27499682
TI - Genome-assisted Breeding For Drought Resistance.
AB - Drought stress caused by unpredictable precipitation poses a major threat to food
production worldwide, and its impact is only expected to increase with the
further onset of climate change. Understanding the effect of drought stress on
crops and plants' response is critical for developing improved varieties with
stable high yield to fill a growing food gap from an increasing population
depending on decreasing land and water resources. When a plant encounters drought
stress, it may use multiple response types, depending on environmental
conditions, drought stress intensity and duration, and the physiological stage of
the plant. Drought stress responses can be divided into four broad types: drought
escape, drought avoidance, drought tolerance, and drought recovery, each
characterized by interacting mechanisms, which may together be referred to as
drought resistance mechanisms. The complex nature of drought resistance requires
a multi-pronged approach to breed new varieties with stable and enhanced yield
under drought stress conditions. High throughput genomics and phenomics allow
marker-assisted selection (MAS) and genomic selection (GS), which offer rapid and
targeted improvement of populations and identification of parents for rapid
genetic gains and improved drought-resistant varieties. Using these approaches
together with appropriate genetic diversity, databases, analytical tools, and
well-characterized drought stress scenarios, weather and soil data, new varieties
with improved drought resistance corresponding to grower preferences can be
introduced into target regions rapidly.
PMID- 27499683
TI - Genomics Approaches For Improving Salinity Stress Tolerance in Crop Plants.
AB - Salinity is one of the major factors which reduces crop production worldwide.
Plant responses to salinity are highly complex and involve a plethora of genes.
Due to its multigenicity, it has been difficult to attain a complete
understanding of how plants respond to salinity. Genomics has progressed
tremendously over the past decade and has played a crucial role towards providing
necessary knowledge for crop improvement. Through genomics, we have been able to
identify and characterize the genes involved in salinity stress response, map out
signaling pathways and ultimately utilize this information for improving the
salinity tolerance of existing crops. The use of new tools, such as gene
pyramiding, in genetic engineering and marker assisted breeding has tremendously
enhanced our ability to generate stress tolerant crops. Genome editing
technologies such as Zinc finger nucleases, TALENs and CRISPR/Cas9 also provide
newer and faster avenues for plant biologists to generate precisely engineered
crops.
PMID- 27499684
TI - Exploring Genetic Diversity in Plants Using High-Throughput Sequencing
Techniques.
AB - Food security has emerged as an urgent concern because of the rising world
population. To meet the food demands of the near future, it is required to
improve the productivity of various crops, not just of staple food crops. The
genetic diversity among plant populations in a given species allows the plants to
adapt to various environmental conditions. Such diversity could therefore yield
valuable traits that could overcome the food-security challenges. To explore
genetic diversity comprehensively and to rapidly identify useful genes and/or
allele, advanced high-throughput sequencing techniques, also called next
generation sequencing (NGS) technologies, have been developed. These provide
practical solutions to the challenges in crop genomics. Here, we review various
sources of genetic diversity in plants, newly developed genetic diversity-mining
tools synergized with NGS techniques, and related genetic approaches such as
quantitative trait locus analysis and genome-wide association study.
PMID- 27499686
TI - Applications of DNA Technologies in Agriculture.
AB - With the development of molecular biology, some DNA-based technologies have
showed great potentiality in promoting the efficiency of crop breeding program,
protecting germplasm resources, improving the quality and outputs of agricultural
products, and protecting the eco-environment etc., making their roles in modern
agriculture more and more important. To better understand the application of DNA
technologies in agriculture, and achieve the goals to promote their utilities in
modern agriculture, this paper describes, in some different way, the applications
of molecular markers, transgenic engineering and gene's information in
agriculture. Some corresponding anticipations for their development prospects are
also made.
PMID- 27499685
TI - Bioinformatics Approach in Plant Genomic Research.
AB - The advance in genomics technology leads to the dramatic change in plant biology
research. Plant biologists now easily access to enormous genomic data to deeply
study plant high-density genetic variation at molecular level. Therefore, fully
understanding and well manipulating bioinformatics tools to manage and analyze
these data are essential in current plant genome research. Many plant genome
databases have been established and continued expanding recently. Meanwhile,
analytical methods based on bioinformatics are also well developed in many
aspects of plant genomic research including comparative genomic analysis,
phylogenomics and evolutionary analysis, and genome-wide association study.
However, constantly upgrading in computational infrastructures, such as high
capacity data storage and high performing analysis software, is the real
challenge for plant genome research. This review paper focuses on challenges and
opportunities which knowledge and skills in bioinformatics can bring to plant
scientists in present plant genomics era as well as future aspects in critical
need for effective tools to facilitate the translation of knowledge from new
sequencing data to enhancement of plant productivity.
PMID- 27499687
TI - Low carbohydrate diet-based intervention for obstructive sleep apnea and primary
hypothyroidism in an obese Japanese man.
AB - BACKGROUND: Obesity is a major risk factor for obstructive sleep apnea (OSA), and
weight loss is necessary in the overall management of obese patients with OSA.
However, primary care physicians can provide only limited weight loss with
lifestyle interventions, usually reducing a patient's body weight by only 2.5 kg
or less after 6-18 months. CASE PRESENTATION: A 45-year-old Japanese man was
referred to our clinic owing to obesity, daytime sleepiness, and snoring during
sleep. His weight was 130.7 kg and his body mass index (BMI) was 41.0 kg/m(2). He
underwent polysomnography, which revealed OSA with an apnea-hypopnea index of
71.2 events/h (normal, <5 events/h). His laboratory results were as follows:
thyroid stimulating hormone, >500 MUIU/mL; free triiodothyronine, 1.4 pg/mL; free
thyroxine, <0.15 ng/dL; thyroid peroxidase antibody, 10 IU/mL; thyroglobulin
antibody, >4000 IU/mL; total cholesterol (TC), 335 mg/dL; high-density
lipoprotein cholesterol, 45 mg/dL; triglycerides (TGs), 211 mg/dL; low-density
lipoprotein cholesterol, 248 mg/dL; fasting blood sugar, 86 mg/dL; and glycated
hemoglobin (HbA1c), 6.1 %. These results showed that he also had primary
hypothyroidism (Hashimoto's disease). Continuous positive airway pressure (CPAP),
levothyroxine replacement, and a low-carbohydrate diet (LCD) were initiated. CPAP
use and a euthyroid condition induced by 175 MUg/day levothyroxine allowed the
patient to proactively reduce his body weight. After 18 months, the patient
achieved a weight reduction of 32.4 kg (25 % of his initial weight) and a BMI
reduction of 10.2 kg/m(2), as well as improved laboratory results, including an
HbA1c level of 5.3 %, TC level of 194 mg/dL, and TG level of 89 mg/dL.
CONCLUSION: An LCD may be an effective intervention for weight loss in obese
Japanese patients with OSA. Further studies are needed to investigate the weight
loss effect of an LCD compared with a conventional calorie-restricted diet.
Hopefully, this case report will help to improve the management of obese Asian
patients with OSA who typically consume a higher amount of carbohydrates.
PMID- 27499688
TI - Pain Characteristics after Total Laparoscopic Hysterectomy.
AB - Background. Total laparoscopic hysterectomy (TLH) causes various types of
postoperative pain, and the pain pattern has not been evaluated in detail to
date. This prospective observational study investigated the types of
postoperative pain, intensity in the course of time, and pain characteristics
during the first postoperative 72 hr after TLH. Methods. Sixty four female
patients undergoing TLH were enrolled, which finally 50 patients were included
for the data analyses. The locations of pain included overall pain, abdominal
visceral and incisional pains, shoulder pain, and perineal pain. Assessments were
made at rest and in motion, and pain level was scored with the use of the 100 mm
visual analog scale. The pain was assessed at baseline, and at postoperative 30
min, 1 hr, 3 hr, 6 hr, 24 hr, 48 hr, and 72 hr. Results. Overall, visceral, and
incisional pains were most intense on the day of operation and then decreased
following surgery. In contrast, shoulder pain gradually increased, peaking at
postoperative 24 hr. Shoulder pain developed in 90% of all patients (44/50). It
was not more aggravated in motion than at rest, in comparison with other pains,
and right shoulder pain was more severe than left shoulder pain (p=0.006). In
addition, the preoperative exercise habit of patients increased the threshold of
shoulder pain. Most patients (46/50) had perineal pain, which was more severe
than abdominal pain in approximately 30% of patients (17/50). Conclusion. Pain
after TLH showed considerably different duration, severity, and characteristics,
compared with other laparoscopic procedures. Shoulder pain was most intense at
postoperative 24 hr, and the intensity was associated with the prior exercise
habit of patients and the high level of analgesic request.
PMID- 27499689
TI - Heat-killed Lactobacillus Reuteri GMNL-263 Prevents Epididymal Fat Accumulation
and Cardiac Injury in High-Calorie Diet-Fed Rats.
AB - High-calorie diet-induced obesity leads to cardiomyocyte dysfunction and
apoptosis. Impaired regulation of epididymal fat content in obese patients has
been known to increase the risk of cardiac injury. In our study, a lactic acid
bacteria, Lactobacillus reuteri GMNL-263, was evaluated for its potential to
reduce body weight and body fat ratio and to prevent heart injury in rats with
high-fat diet-induced obesity. Lactic acid bacteria supplementation restored the
cardiac function and decreased the physiological changes in the heart of the
obese rats. In addition, the Fas/Fas-associated protein pathway-induced caspase
3/e Poly polymerase mediated apoptosis in the cardiomyocytes of the obese rats
was reversed in the Lr263-treated rats. These results reveal that fed with Lr-263
reduces body fat ratio, inhibits caspase 3-mediated apoptosis and restores
cardiac function in obese rats through recovery of ejection fraction and
fractional shortening. Our results indicated that the administration of Lr263
lactic acid bacteria can significantly down-regulate body fat and prevent
cardiomyocyte injury in obese rats.
PMID- 27499690
TI - Progress on Complications of Direct Bypass for Moyamoya Disease.
AB - Moyamoya disease (MMD) involves progressive occlusion of the intracranial
internal carotid artery resulting in formation of moyamoya-like vessels at the
base of the brain. It can be characterized by hemorrhage or ischemia. Direct
vascular bypass is the main and most effective treatment of MMD. However,
patients with MMD differ from those with normal cerebral vessels. MMD patients
have unstable intracranial artery hemodynamics and a poor blood flow reserve;
therefore, during the direct bypass of superficial temporal artery (STA)-middle
cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can
affect the hemodynamics of these patients. When brain tissue cannot tolerate a
high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to
neurological function defects and can even cause intracranial hemorrhage in
severe cases. The brain tissue is prone to infarction when hemodynamic
equilibrium is affected. In addition, bypass vessels become susceptible to
occlusion or atrophy when blood resistance increases. Even compression of the
temporalis affects bypass vessels. Because the STA is used in MMD surgery, the
scalp becomes ischemic and is likely to develop necrosis and infection. These
complications of MMD surgery are difficult to manage and are not well understood.
To date, no systematic studies of the complications that occur after direct
bypass in MMD have been performed, and reported complications are hidden among
various case studies; therefore, this paper presents a review and summary of the
literature in PubMed on the complications of direct bypass in MMD.
PMID- 27499691
TI - The Neutrophil to Lymphocyte Ratio on Admission and Short-Term Outcomes in
Orthogeriatric Patients.
AB - AIM: To investigate the association of the neutrophil to lymphocyte ratio (NLR)
at admission with presence of fracture, comorbid conditions, and its prognostic
value for short-term outcomes in orthogeriatric patients. METHODS: On 415
consecutive patients (mean age 78.8 +/-8.7[SD] years, 281 women, 255 with a non
vertebral bone fracture, including 167 with a hip fracture, HF) admitted to the
Department of Orthopaedic Surgery at the Canberra hospital (2010 - 2011) data on
clinical and laboratory characteristics were collected prospectively. The
validation dataset included 294 consecutive patients (mean age 82.1 +/- 8.0
years, 72.1% women) with HF. RESULTS: Multivariate regression revealed four
variables, presence of HF, hypoalbuminaemia (<33g/L), anaemia (<120g/L) and
hyperparathyroidism (PTH>6.8 pmol/L), as independent determinants of admission
NLR>=5.1. There was a dose-graded relationship between presence of fracture,
especially HF, postoperative complications and levels of NLR categorized as
tertiles. Compared to patients with NLR<5.1(first tertile), patients with NLR 5.1
8.5 (second tertile) had a 1.8-, 3.1-, 2.6-, and 2.5-fold higher risk for
presence of any fracture, HF, developing postoperative myocardial injury
(troponin I rise) and a high inflammatory response/infection (CRP>100mg/L after
the 3rd postoperative day), respectively, while in subjects with NLR>8.5 (third
tertile) these risks were 2.6-, 4.9-, 5.9- and 4.5-times higher, respectively;
subjects with NLR>8.5 had a 9.7 times higher chance of dying in the hospital
compared to patients with NLR 5.1-8.5; the NLR retained its significance on
multivariate analyses. The NLR >=5.1 predicted postoperative myocardial injury
with an area under the curve (AUC) of 0.626, CRP>100mg/L with AUC of 0.631 and
the NLR >8.5 predicted in-hospital mortality with an AUC of 0.793, showing
moderately high sensitivity (86.7%, 80% and 90%, respectively) and negative
predictive value (92.9%, 71.2%, 99.6%, respectively), but low specificity.
Admission NLR was superior to other, except hypoalbuminaemia, prognostic markers;
combined use of both NLR>=5.1 and albumin<33g/L only moderately increased the
accuracy of prediction. The validation study confirmed the prognostic value of
the admission NLR. CONCLUSIONS: In orthogeriatric patients, high NLR on admission
is an independent indicator of fracture presence, a significant risk factor and
moderate predictor of postoperative myocardial injury, high inflammatory
response/infection and in-hospital death.
PMID- 27499692
TI - Wnt5a Suppresses beta-catenin Signaling during Hair Follicle Regeneration.
AB - Hair follicles display periodic growth. Wnt signaling is a critical regulator for
hair follicle regeneration. Previously, we reported that Wnt5a inhibits the
telogen-to-anagen transition of hair follicles, but the mechanism by which this
process occurs has not yet been reported. Here, we determined the expression
patterns of Wnt signaling pathway molecules by quantitative reverse transcription
polymerase chain reaction, western blot, and immunohistochemistry and found that
beta-catenin signaling was suppressed by Wnt5a. We then compared the phenotypes
and expression patterns following beta-catenin knockdown and Wnt5a overexpression
during hair follicle regeneration induced by hair depilation and observed similar
patterns. In addition, we performed a rescue experiment in the JB6 cell line and
found that the inhibitory effect of Wnt5a on cell proliferation could be rescued
by the addition of Wnt3a. Our data reveal that Wnt5a suppresses the activation of
beta-catenin signaling during hair follicle regeneration.
PMID- 27499693
TI - NLS-RARalpha Inhibits the Effects of All-trans Retinoic Acid on NB4 Cells by
Interacting with P38alpha MAPK.
AB - Nuclear localization signal retinoic acid receptor alpha(NLS-RARalpha), which
forms from the cleavage of promyelocytic leukemia-retinoic acid receptor
alpha(PML-RARalpha) protein by neutrophil elastase(NE), possesses an important
role in the occurrence and development of acute promyelocytic leukemia(APL).
However, the potential mechanism underlying the effects of NLS-RARalpha on APL is
still not entirely clear. Here, we investigated the effects of NLS-RARalpha on
APL NB4 cells and its mechanism. We found that all-trans retinoic acid(ATRA)
could promote differentiation while inhibit proliferation of APL NB4 cells via
upregulating the expression of phosphorylated p38alpha mitogen-activated protein
kinase(p-p38alpha MAPK). We also found that NLS-RARalpha could inhibit
differentiation while accelerate proliferation of NB4 cells via downregulating
the expression of p-p38alpha protein in the presence of ATRA. Furthermore,
immunofluorescence and co-immunoprecipitation assays confirmed NLS-RARalpha
interacted with p38alpha protein directly. Finally, application of PD169316, an
inhibitor of p38alpha protein, suggested that recruitment p38alpha-combinded NLS
RARalpha by ATRA eventually caused activation of p38alpha protein. In summary,
our study demonstrated that ATRA cound promote differentiation while inhibit
proliferation of APL NB4 cells via activating p38alpha protein after recruiting
p38alpha-combinded NLS-RARalpha, while NLS-RARalpha could inhibit the effects of
ATRA in the process.
PMID- 27499694
TI - Predictive Value of Echocardiographic Abnormalities and the Impact of Diastolic
Dysfunction on In-hospital Major Cardiovascular Complications after Living Donor
Kidney Transplantation.
AB - Patients with end-stage renal disease (ESRD) show characteristic abnormalities in
cardiac structure and function. We evaluated the influence of these abnormalities
on adverse cardiopulmonary outcomes after living donor kidney transplantation in
patients with valid preoperative transthoracic echocardiographic evaluation. We
then observed any development of major postoperative cardiovascular complications
and pulmonary edema until hospital discharge. In-hospital major cardiovascular
complications were defined as acute myocardial infarction, ventricular
fibrillation/tachycardia, cardiogenic shock, newly-onset atrial fibrillation,
clinical pulmonary edema requiring endotracheal intubation or dialysis. Among the
242 ESRD study patients, 9 patients (4%) developed major cardiovascular
complications, and 39 patients (16%) developed pulmonary edema. Diabetes,
ischemia-reperfusion time, left ventricular end-diastolic diameter (LVEDd), left
ventricular mass index (LVMI), right ventricular systolic pressure (RVSP), left
atrium volume index (LAVI), and high E/E' ratios were risk factors of major
cardiovascular complications, while age, LVEDd, LVMI, LAVI, and high E/E' ratios
were risk factors of pulmonary edema. The optimal E/E' cut-off value for
predicting major cardiovascular complications was 13.0, showing 77.8% sensitivity
and 78.5% specificity. Thus, the patient's E/E' ratio is useful for predicting in
hospital major cardiovascular complications after kidney transplantation. We
recommend that goal-directed therapy employing E/E' ratio be enacted in kidney
recipients with baseline diastolic dysfunction to avert postoperative morbidity.
(http://Clinical Trials.gov number: NCT02322567).
PMID- 27499695
TI - Role of the ERK1/2 Signaling Pathway in Osteogenesis of Rat Tendon-Derived Stem
Cells in Normoxic and Hypoxic Cultures.
AB - BACKGROUND: Ectopic ossification and increased vascularization are two common
phenomena in the chronic tendinopathic tendon. The increased vascularization
usually leads to an elevated local oxygen tension which is one of micro
environments that can influence differentiate status of stem cells. OBJECTIVE:
This study aimed to investigate the osteogenesis capacity of rat tendon-derived
stem cells TDSCs (rTDSCs) in normoxic and hypoxic cultures, and to study the role
of ERK1/2 signaling pathway in this process. METHODS: rTDSCs were subjected to
osteogenesis inductive culture in hypoxic (3% O2) and normoxic (20% O2)
conditions. The inhibitor U0126 was added along with culture medium to determine
the role of ERK1/2 signaling pathway. Cell viability, cell proliferation,
alizarin red staining, alkaline phosphatase (AKP) activity, gene expression (ALP,
osteocalcin, collagen I and RUNX2) and protein expression (p-ERK1/2 and RUNX2) of
osteogenic-cultured rTSDCs were analyzed in this study. RESULTS: Hypoxic and
normoxic culture had no effects on cell viability of rTDSCs, whereas the
proliferation potential of rTDSCs was significantly increased in hypoxic culture.
The osteogenesis capacity of rTDSCs in normoxic culture was significantly
promoted compared with hypoxic culture, which was reflected by an increased
alizarin red staining intensity, an elevated ALP activity, and the up-regulated
gene (ALP, osteocalcin, collagen I and RUNX2) or protein (RUNX2) expression of
osteogenic makers. However, the osteogenesis capacity of rTDSCs in both hypoxic
and normoxic cultures was attenuated by the inhibitor U0126. CONCLUSION: Normoxic
culture promotes osteogenic differentiation of rTDSCs compared with the hypoxic
culture, and the ERK1/2 signaling pathway is involved in this process.
PMID- 27499696
TI - Elevated Plasma Matrix Metalloproteinase-9 and Its Correlations with Severity of
Disease in Patients with Ventilator-Associated Pneumonia.
AB - Ventilator-associated pneumonia (VAP) increases patient mortality and medical
expenditure, and a real-time and reliable method for the rapid diagnosis of VAP
may help reduce fatal complications. Matrix metalloproteinases-9 (MMP-9) is
considered significant in the pathogenesis of lung inflammation and infection.
Therefore, we examined its relationship with the clinical course of VAP. This
retrospective observational study recruited 30 healthy volunteers, 12 patients
who used mechanical ventilation without the development of VAP (hereafter,
patients without VAP), and 30 patients with a clinical diagnosis of VAP
(hereafter, patients with VAP). The activity and level of plasma MMP-9 were
determined through a gelatin zymography assay and ELISA. Our results report that
both plasma MMP-9 activity and concentration were significantly elevated in the
acute stage of patients with VAP when compared with control group and patients
without VAP (p < 0.001). Subsequently, the plasma MMP-9 of patients with VAP
decreased significantly after antibiotic treatment. Furthermore, plasma MMP-9
concentration was positively correlated with the clinical pulmonary infection
score (r = 0.409, p = 0.007), WBCs (r = 0.620, p < 0.001), and neutrophils counts
(r = 0.335, p = 0.035). In addition, plasma MMP-9 is an excellent tool for
recognizing VAP when the cutoff level is set to 92.62 ng/mL (AUC = 0.863, 95% CI
= 0.761 to 0.932). In conclusions, we concluded that MMP-9 levels play a role in
the development of VAP and might have the potential to be applied in the
development of VAP therapies.
PMID- 27499697
TI - NOX2 Antisense Attenuates Hypoxia-Induced Oxidative Stress and Apoptosis in
Cardiomyocyte.
AB - Heart ischemia is a hypoxia related disease. NOX2 and HIF-1alpha proteins were
increased in cardiomyocytes after acute myocardial infarction. However, the
relationship of the hypoxia-induced HIF-1alpha. NOX2-derived oxidative stress and
apoptosis in cardiomyocyte remains unclear. In the current study, we use NOX2
antisense strategy to investigate the role of NOX2 in hypoxia-induced oxidative
stress and apoptosis in rat cardiomyocytes. Here, we show that transduction of
ADV-NOX2-AS induces potent silencing of NOX2 in cardiomyocytes, and resulting in
attenuation of hypoxia-induced oxidative stress and apoptosis. This study
indicates the potential of antisense-based therapies and validates NOX2 as a
potent therapeutic candidate for heart ischemia.
PMID- 27499698
TI - Cross-scale integration of knowledge for predicting species ranges: a
metamodeling framework.
AB - AIM: Current interest in forecasting changes to species ranges have resulted in a
multitude of approaches to species distribution models (SDMs). However, most
approaches include only a small subset of the available information, and many
ignore smaller-scale processes such as growth, fecundity, and dispersal.
Furthermore, different approaches often produce divergent predictions with no
simple method to reconcile them. Here, we present a flexible framework for
integrating models at multiple scales using hierarchical Bayesian methods.
LOCATION: Eastern North America (as an example). METHODS: Our framework builds a
metamodel that is constrained by the results of multiple sub-models and provides
probabilistic estimates of species presence. We applied our approach to a
simulated dataset to demonstrate the integration of a correlative SDM with a
theoretical model. In a second example, we built an integrated model combining
the results of a physiological model with presence-absence data for sugar maple
(Acer saccharum), an abundant tree native to eastern North America. RESULTS: For
both examples, the integrated models successfully included information from all
data sources and substantially improved the characterization of uncertainty. For
the second example, the integrated model outperformed the source models with
respect to uncertainty when modelling the present range of the species. When
projecting into the future, the model provided a consensus view of two models
that differed substantially in their predictions. Uncertainty was reduced where
the models agreed and was greater where they diverged, providing a more realistic
view of the state of knowledge than either source model. MAIN CONCLUSIONS: We
conclude by discussing the potential applications of our method and its
accessibility to applied ecologists. In ideal cases, our framework can be easily
implemented using off-the-shelf software. The framework has wide potential for
use in species distribution modelling and can drive better integration of multi
source and multi-scale data into ecological decision-making.
PMID- 27499699
TI - Review article: outcomes in endoscopic sinus surgery.
AB - Chronic rhinosinusitis has a significant impact on health-related and generic
quality-of-life, has a high cost burden to both society and patients, and may be
associated with absenteeism, loss of productivity and poor respiratory function.
Though there is a paucity of level 1 evidence, endoscopic sinus surgery may be
considered in medically refractory patients and a variety of objective and
subjective outcome measures exist to assess the effectiveness of intervention. We
outline the outcome measurements available and review in-depth the published
outcomes to date. Furthermore we discuss the literature that indicates that
endoscopic sinus surgery can have a positive effect on respiratory function in
asthma. How patient selection, timing and extent of surgery, and post-operative
care interventions may optimise surgical outcomes is explored.
PMID- 27499700
TI - Tinnitus- related distress: evidence from fMRI of an emotional stroop task.
AB - BACKGROUND: Chronic tinnitus affects 5 % of the population, 17 % suffer under the
condition. This distress seems mainly to be dependent on negative cognitive
emotional evaluation of the tinnitus and selective attention to the tinnitus. A
well-established paradigm to examine selective attention and emotional processing
is the Emotional Stroop Task (EST). Recent models of tinnitus distress propose
limbic, frontal and parietal regions to be more active in highly distressed
tinnitus patients. Only a few studies have compared high and low distressed
tinnitus patients. Thus, this study aimed to explore neural correlates of
tinnitus-related distress. METHODS: Highly distressed tinnitus patients (HDT, n =
16), low distressed tinnitus patients (LDT, n = 16) and healthy controls (HC, n =
16) underwent functional magnetic resonance imaging (fMRI) during an EST, that
used tinnitus-related words and neutral words as stimuli. A random effects
analysis of the fMRI data was conducted on the basis of the general linear model.
Furthermore correlational analyses between the blood oxygen level dependent
response and tinnitus distress, loudness, depression, anxiety, vocabulary and
hypersensitivity to sound were performed. RESULTS: Contradictory to the
hypothesis, highly distressed patients showed no Stroop effect in their reaction
times. As hypothesized HDT and LDT differed in the activation of the right insula
and the orbitofrontal cortex. There were no hypothesized differences between HDT
and HC. Activation of the orbitofrontal cortex and the right insula were found to
correlate with tinnitus distress. CONCLUSIONS: The results are partially
supported by earlier resting-state studies and corroborate the role of the insula
and the orbitofrontal cortex in tinnitus distress.
PMID- 27499701
TI - Dried blood spot omega-3 and omega-6 long chain polyunsaturated fatty acid levels
in 7-9 year old Zimbabwean children: a cross sectional study.
AB - BACKGROUND: Omega-3 long chain-polyunsaturated fatty acids (LC-PUFAs)
docosahexaenoic acid (DHA), docosapentaenoic acid (DPA) and eicosapentaenoic acid
(EPA)- and omega-6 LC-PUFA arachidonic acid (ARA), are essential for optimum
physical and mental development in children. Prior to this study, the blood omega
3 LC-PUFA levels were unknown in Zimbabwean children, particularly in those aged
7-9 years, despite the documented benefits of LC-PUFAs. Documentation of the LC
PUFA levels in this age group would help determine whether interventions, such as
fortification, are necessary. This study aimed to determine dried whole blood
spot omega-3 and omega-6 LC-PUFA levels and LC-PUFA reference intervals among a
selected group of Zimbabwean children aged 7-9 years old. METHODS: We conducted a
cross sectional study from September 2011 to August 2012 on a cohort of peri
urban, Zimbabwean children aged 7-9 years. The children were born to mothers
enrolled at late pregnancy into an HIV prevention program between 2002 and 2004.
Dried whole blood spots were sampled on butylated hydroxytoluene antioxidant
impregnated filter papers and dried. LC-PUFAs were quantified using gas liquid
chromatography. Differences in LC-PUFAs between groups were compared using the
Kruskal Wallis test and reference intervals determined using non-parametric
statistical methods. RESULTS: LC-PUFAs levels were determined in 297 Zimbabwean
children of whom 170 (57.2 %) were girls. The study determined that LC-PUFAs
(wt/wt) ranges were EPA 0.06-0.55 %, DPA 0.38-1.98 %, DHA 1.13-3.52 %, ARA 5.58
14.64 % and ARA: EPA ratio 15.47-1633.33. Sixteen participants had omega-3 LC
PUFAs levels below the determined reference intervals, while 18 had higher omega
6 LC-PUFAs. The study did not show gender differences in omega-3 and omega-6 LC
PUFAs levels (all p > 0.05). EPA was significantly higher in the 8 year age group
compared to those aged 7 and 9 years (median; 0.20 vs 0.17 vs 0.18, respectively,
p = 0.049). ARA: EPA ratio was significantly higher in the 7 year age group
compared to those aged 8 and 9 years (median; 64.38 vs 56.43 vs 55.87
respectively, p = 0.014). CONCLUSIONS: In this cohort of children, lower EPA
levels and higher ARA: EPA ratios were observed compared to those reported in
apparently healthy children elsewhere. The high ARA: EPA ratios might increase
the vulnerability of these children to inflammatory pathologies. Identification
and incorporation into diet of locally produced foodstuffs rich in omega-3 LC
PUFAs is recommended as well as advocating for dietary supplementation with omega
3 fish oils and algae based oils.
PMID- 27499702
TI - Pre-term and post-term births: predictors and implications on neonatal mortality
in Northern Ethiopia.
AB - BACKGROUND: Pre-term and post-term births are major determinants of neonatal
mortality, including short- and long-term morbidity. In developing countries,
where pre-term and post-term births are disproportionately common, the magnitude
and underlying causes are not well understood, and evidence is required to design
appropriate interventions. This study measured the incidence and identified risk
factors of pre-term birth and post-term births in Ethiopia. In addition, it
examined the effects of pre-term and post-term birth on neonatal mortality.
METHOD: This study is a portion of prospective cohort study conducted on 1152
live births born between April and July 2014 in seven hospitals in Tigray region,
Northern Ethiopia. Neonatal mortality and birth outcomes were considered as
dependent variables. Data were collected using a structured questionnaire and
weekly neonatal follow up directed at midwives. Data were described using
frequency, percentage, ratio of relative risk (RRR), and 95 % confidence interval
(CI). We used multinomial and binary logistic regression to identify independent
predictors of birth outcome and neonatal mortality respectively. RESULT: The
prevalence of pre-term and post term births was 8.1 % and 6.0 % respectively.
Underweight maternal body mass index (RRR: 0.47, CI: 0.22-0.99), medium reported
income (RRR: 0.26, CI: 0.12-0.5), length of neonate (RRR: 0.05, CI: 0.01-0.41),
and multiple births (RRR: 2.86, CI: 1.4-5.650) were associated with pre-term
birth. Predictors for post-term birth were overweight maternal body mass index
(RRR: 3.88, CI: 1.01-15.05), high reported income mothers (RRR: 2.17, CI:1.1
4.3), as well as unmarried, widowed and divorced marital status (RRR:2.43,
CI:1.02-5.80). With regards to binary logistic regression, pre-term birth (RR:
2.45, CI: 1.45-4.04) was an independent predictor for neonatal mortality, but
this was not true for post-term births (RR: 0.45, CI: 0.07-2.96). CONCLUSION:
Socioeconomic and proximate factors are important predictors for pre-term and
post-term births. Empowering women in terms of income status and controlling body
mass index within the normal range are recommended. In addition, early detection
and close antenatal follow-ups for mothers, who are at risk before and during
pregnancy, are necessary to prevent both pre-term and post-term births.
PMID- 27499703
TI - MiR-20a-5p represses multi-drug resistance in osteosarcoma by targeting the
KIF26B gene.
AB - BACKGROUND: Chemoresistance hinders curative cancer chemotherapy in osteosarcoma
(OS), resulting in only an approximately 20 % survival rate in patients with
metastatic disease at diagnosis. Identifying the mechanisms responsible for
regulating chemotherapy resistance is crucial for improving OS treatment.
METHODS: This study was performed in two human OS cell lines (the multi
chemosensitive OS cell line G-292 and the multi-chemoresistant OS cell line SJSA
1). The levels of miR-20a-5p and KIF26B mRNA expression were determined by
quantitative real-time PCR. KIF26B protein levels were determined by western blot
analysis. Cell viability was assessed by MTT assay. Apoptosis was evaluated by
flow cytometry. RESULTS: We found that miR-20a-5p was more highly expressed in G
292 cells than in SJSA-1 cells. Forced expression of miR-20a-5p counteracted OS
cell chemoresistance in both cell culture and tumor xenografts in nude mice. One
of miR-20a-5p's targets, kinesin family member 26B (KIF26B), was found to mediate
the miR-20a-5p-induced reduction in OS chemoresistance by modulating the
activities of the MAPK/ERK and cAMP/PKA signaling pathways. CONCLUSIONS: In
addition to providing mechanistic insights, our study revealed that miR-20a-5p
and KIF26B contribute to OS chemoresistance and determined the roles of these
genes in this process, which may be critical for characterizing drug
responsiveness and overcoming chemoresistance in OS patients.
PMID- 27499704
TI - Vitamin D3 improves the effects of low dose Der p 2 allergoid treatment in Der p
2 sensitized BALB/c mice.
AB - BACKGROUND: Airborne allergens can induce an immunological chronic disease
characterized by airway hyper responsiveness and inflammation, mediated by
exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is
effective for treating this condition because it is able to modify its natural
course by opposing the underlying pathogenic mechanisms and determining immune
suppression, immune deviation and tolerance. The rational for the present study
was to investigate the possibility of improving allergoid-based IT in terms of
efficacy and safety. Recently, 1alpha,25-dihydroxyvitamin D3 (VD3), the active
metabolite of vitamin D3, was described to be a potent inducer of T regulatory
cells and to be a good adjuvant in AIT settings. METHODS: We investigated whether
the co-administration of VD3 could potentiate the effect of AIT even when added
to a low dose of chemically-modified monomeric allergoid of Der p 2 (d2-OID), in
a Derp p 2 (d2)-sensitized BALB/c mice model. Control groups where treated with
sham, VD3 alone or d2-OID only. RESULTS: The d2-OID alone was not fully
successful, as expected for a low dose. VD3 administration was associated with
some valuable, although limited, changes in the immunological parameters in the
lung. On the contrary, the VD3 adjuvated allergoid vaccine induced the most
prominent reduction of airway eosinophilia and Th2 cytokines and concomitant
increase of T regulatory cells and IL-10 in the lung and Der p 2-specific IgG2a
in the serum. CONCLUSIONS: The addition of VD3 to a conventional AIT protocol
would allow the reduction of allergoid dose needed and therefore, the production
costs. Moreover, beneficial immunomodulatory effects have been achieved by the
oral administration which might favour the management of the therapy by the
patients and their adherence, possibly enhancing the efficacy of the treatment.
PMID- 27499705
TI - The Utility of Template Analysis in Qualitative Psychology Research.
AB - Thematic analysis is widely used in qualitative psychology research, and in this
article, we present a particular style of thematic analysis known as Template
Analysis. We outline the technique and consider its epistemological position,
then describe three case studies of research projects which employed Template
Analysis to illustrate the diverse ways it can be used. Our first case study
illustrates how the technique was employed in data analysis undertaken by a team
of researchers in a large-scale qualitative research project. Our second example
demonstrates how a qualitative study that set out to build on mainstream theory
made use of the a priori themes (themes determined in advance of coding)
permitted in Template Analysis. Our final case study shows how Template Analysis
can be used from an interpretative phenomenological stance. We highlight the
distinctive features of this style of thematic analysis, discuss the kind of
research where it may be particularly appropriate, and consider possible
limitations of the technique. We conclude that Template Analysis is a flexible
form of thematic analysis with real utility in qualitative psychology research.
PMID- 27499706
TI - Severe personality disorder, treatment engagement and the Legal Aid, Sentencing
and Punishment of Offenders Act 2012: what you need to know.
AB - Empirical research has demonstrated a link between legal coercion and treatment
engagement following conviction among those with severe personality disorder.
Legal coercive pressures were often applied by the Indeterminate Sentence for
Public Protection (IPP), until it was replaced by the Extended Determinate
Sentence by the Legal Aid, Sentencing and Punishment of Offenders Act 2012. In
this paper, it is proposed that use of the new determinate sentence will lessen
motivation for treatment engagement. One effect of treatment refusal may be
greater reliance by the Secretary of State for Justice on his jurisdiction to
transfer prisoners due for release to secure hospital transfers under the Mental
Health Act 1983. Not only will this risk posturing undermine the principal aim of
the Offender Personality Disorder Implementation Pathway to improve treatment
engagement among the target group, it will also have negative implications for
medical practitioners working in secure forensic hospitals. To demonstrate what
is at stake, the paper briefly recapitulates empirical findings familiar to
readers of the journal, before drawing on original unpublished data.
PMID- 27499707
TI - Measuring Community Resilience to Coastal Hazards along the Northern Gulf of
Mexico.
AB - The abundant research examining aspects of social-ecological resilience,
vulnerability, and hazards and risk assessment has yielded insights into these
concepts and suggested the importance of quantifying them. Quantifying resilience
is complicated by several factors including the varying definitions of the term
applied in the research, difficulties involved in selecting and aggregating
indicators of resilience, and the lack of empirical validation for the indices
derived. This paper applies a new model, called the resilience inference
measurement (RIM) model, to quantify resilience to climate-related hazards for 52
U.S. counties along the northern Gulf of Mexico. The RIM model uses three
elements (exposure, damage, and recovery indicators) to denote two relationships
(vulnerability and adaptability), and employs both K-means clustering and
discriminant analysis to derive the resilience rankings, thus enabling validation
and inference. The results yielded a classification accuracy of 94.2% with 28
predictor variables. The approach is theoretically sound and can be applied to
derive resilience indices for other study areas at different spatial and temporal
scales.
PMID- 27499708
TI - Tension on dsDNA bound to ssDNA-RecA filaments may play an important role in
driving efficient and accurate homology recognition and strand exchange.
AB - It is well known that during homology recognition and strand exchange the double
stranded DNA (dsDNA) in DNA/RecA filaments is highly extended, but the functional
role of the extension has been unclear. We present an analytical model that
calculates the distribution of tension in the extended dsDNA during strand
exchange. The model suggests that the binding of additional dsDNA base pairs to
the DNA/RecA filament alters the tension in dsDNA that was already bound to the
filament, resulting in a non-linear increase in the mechanical energy as a
function of the number of bound base pairs. This collective mechanical response
may promote homology stringency and underlie unexplained experimental results.
PMID- 27499709
TI - Fast Sequential Creation of Random Realizations of Degree Sequences.
AB - We examine the problem of creating random realizations of very large degree
sequences. Although fast in practice, the Markov chain Monte Carlo (MCMC) method
for selecting a realization has limited usefulness for creating large graphs
because of memory constraints. Instead, we focus on sequential importance
sampling (SIS) schemes for random graph creation. A difficulty with SIS schemes
is assuring that they terminate in a reasonable amount of time. We introduce a
new sampling method by which we guarantee termination while achieving speed
comparable to the MCMC method.
PMID- 27499710
TI - Personalizing Patient Care.
PMID- 27499711
TI - Gastro-Hep News.
PMID- 27499712
TI - Metabolic Manifestations and Complications Associated With Chronic Hepatitis C
Virus Infection.
AB - Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic
manifestations that contribute to morbidity and mortality. It is especially
important to be aware of metabolic manifestations and serious complications that
affect other organs and cancer risks. Chronic HCV infection itself contributes to
de novo development of insulin resistance and hepatic steatosis, both of which
increase the risk of cardiovascular diseases. Through these metabolic pathways
(as well as through other hypothesized mechanisms that involve lipid metabolism,
systemic inflammatory signals, and endothelial dysfunction), chronic HCV
infection also contributes to significant systemic cardiovascular morbidity and
mortality. While chronic HCV infection contributes to incident development of
metabolic complications, the presence of concurrent metabolic diseases also
contributes to disease progression, such as higher risks of hepatocellular
carcinoma and progression to advanced fibrosis, among patients with chronic HCV
infection. The implications of these observations are particularly important
given the rising prevalence of obesity and metabolic syndrome in the United
States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease,
either as a result of underlying metabolic syndrome or as a direct result of HCV
induced fatty liver disease, further complicates the management of chronic HCV
infected patients. Greater awareness is needed toward the systemic manifestations
of chronic HCV infection, with focused attention on the associated metabolic
manifestations and complications. Successful treatment and cure of chronic HCV
infection with the currently available, highly effective antiviral therapies will
significantly improve long-term outcomes among these patients. It is also
important to recognize and address the associated metabolic manifestations and
complications to reduce cardiovascular-related morbidity and mortality.
PMID- 27499714
TI - Henoch-Schonlein Purpura With Gastrointestinal Involvement in an Adult Patient.
PMID- 27499713
TI - A Personalized Approach to Managing Inflammatory Bowel Disease.
AB - The management of inflammatory bowel disease (IBD) requires a personalized
approach to treat what is a heterogeneous group of patients with inherently
variable disease courses. In its current state, personalized care of the IBD
patient involves identifying patients at high risk for rapid progression to
complications, selecting the most appropriate therapy for a given patient, using
therapeutic drug monitoring, and achieving the individualized goal that is most
appropriate for that patient. The growing body of research in this area allows
clinicians to better predict outcomes for individual patients. Some paradigms,
especially within the realm of therapeutic drug monitoring, have begun to change
as therapy is targeted to individual patient results and goals. Future
personalized medical decisions may allow specific therapeutic plans to draw on
serologic, genetic, and microbial data for Crohn's disease and ulcerative colitis
patients.
PMID- 27499715
TI - Effects of Opioids on Esophageal Dysfunction.
PMID- 27499716
TI - Sedation in Colonoscopy.
PMID- 27499717
TI - Management of Lysosomal Acid Lipase Deficiency for the Gastroenterologist and
Hepatologist.
PMID- 27499718
TI - Clostridium difficile Infection and Inflammatory Bowel Disease.
PMID- 27499719
TI - Acute Compartment Syndrome of the Lower Leg: A Review.
AB - Acute compartment syndrome (ACS) of the lower leg is a time-sensitive orthopedic
emergency that relies heavily on precise clinical findings. Late findings of ACS
can lead to limb amputation, contractures, paralysis, multiorgan failure, and
death. Hallmark symptoms of ACS include the 6 P's: pain, poikilothermia, pallor,
paresthesia, pulselessness, and paralysis. Suspicion of ACS is confirmed by
measurement of intracompartmental pressure of the affected compartment. The
definitive treatment of ACS is timely fasciotomy. We review the pathophysiology,
common causes, diagnosis, and treatment of this potentially devastating
condition.
PMID- 27499720
TI - Quantification of angiotensin II-regulated proteins in urine of patients with
polycystic and other chronic kidney diseases by selected reaction monitoring.
AB - BACKGROUND: Angiotensin-II (Ang II) mediates progression of autosomal-dominant
polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD).
However, markers of kidney Ang II activity are lacking. We previously defined 83
Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in
vivo. METHODS: In this study, we developed selected reaction monitoring (SRM)
assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD
patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were
differentially expressed in cystic compared to normal kidney tissue. We then
developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts
and/or secreted in urine. Methods that yielded CV <= 6 % for control proteins,
and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13
identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD
patients, 9 patients with CKD predicted to have high kidney Ang II activity and
11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole
mass spectrometer in duplicates. RESLUTS: Calibration curves demonstrated
linearity (R(2) > 0.99) and within-run CVs < 9 % in the concentration range of
7/13 peptides. Peptide concentrations were normalized by urine creatinine.
Deamidated peptide forms were monitored, and accounted for <15 % of the final
concentrations. Urine excretion rates of proteins BST1, LAMB2, LYPA1, RHOB and
TSP1 were significantly different (p < 0.05, one-way ANOVA) between patients with
CKD, those with ADPKD and healthy controls. Urine protein excretion rates were
highest in CKD patients and lowest in ADPKD patients. Univariate analysis
demonstrated significant association between urine protein excretion rates of
most proteins and disease group (p < 0.05, ANOVA) as well as sex (p < 0.05,
unpaired t test). Multivariate analysis across protein concentration, age and sex
demonstrated good separation between ADPKD and CKD patients. CONCLUSIONS: We have
optimized methods for quantification of Ang II-regulated proteins, and we
demonstrated that they reflected differences in underlying kidney disease in this
pilot study. High urine excretion of Ang II-regulated proteins in CKD patients
likely reflects high kidney Ang II activity. Low excretion in ADPKD appears
related to lack of communication between cysts and tubules. Future studies will
determine whether urine excretion rate of Ang II-regulated proteins correlates
with kidney Ang II activity in larger cohorts of chronic kidney disease patients.
PMID- 27499721
TI - Biosynthesis of glycerol phosphate is associated with long-term potentiation in
hippocampal neurons.
AB - INTRODUCTION: Neurons have a very high energy requirement, and their metabolism
is tightly regulated to ensure delivery of adequate substrate to sustain neuronal
activity and neuroplastic changes. The mechanisms underlying the regulation of
neuronal metabolism, however, are not completely clear. OBJECTIVE: The objective
of this study was to investigate the central carbon metabolism in neurons, in
order to identify the regulatory pathways governing neuronal anabolism and
catabolism. METHODS: Here we first have applied MS-based endometabolomics to
elucidate the metabolic dynamics in cultured hippocampal primary neurons. Using
nanoLC-ESI-LTQ Orbitrap MS approach followed by statistical analysis, we measure
the dynamics of uniformly labeled 13C-glucose entering neurons. We adapted the
method by coupling offline patch-clamp setup with MS to confirm findings in vivo.
RESULTS: According to non-parametric statistical analysis of metabolic dynamics,
in cultured hippocampal neurons, the glycerol phosphate shuttle is active and
correlates with the metabolic flux in the pentose phosphate pathway. In the
hippocampus, glycerol-3-phosphate biosynthesis was activated in response to long
term potentiation together with the upregulation of glycolysis and the TCA cycle,
but was inactive or silenced in basal conditions. CONCLUSIONS: We identified the
biosynthesis of glycerol-3-phosphate as a key regulator in mechanisms implicated
in learning and memory. Notably, defects in enzymes linked with the glycerol
phosphate shuttle have been implicated in neurological disorders and intellectual
disability. These results could improve our understanding of the general
mechanisms of learning and memory and facilitate the development of novel
therapies for metabolic disorders linked with intellectual disability.
PMID- 27499722
TI - Bone Marrow-Derived Cells in the Pathogenesis of Lung Fibrosis.
AB - Progressive pulmonary fibrosis is characterized by failed alveolar
reepithelialization and fibroblast/myofibroblast accumulation, with deposition of
extracellular matrix. This results in loss of lung elasticity, alveolar collapse
and fibrosis, impaired gas exchange and progressive decline in pulmonary
function. Myofibroblasts represent an activated, contractile cellular phenotype
that are potent producers of collagen and other extracellular matrix proteins. It
is generally thought that myofibroblasts derive from local tissue fibroblasts.
However, recent evidence suggests a portion of the progenitors for these cells
may arise from the bone marrow. Fibrocytes, which share both leukocyte and
mesenchymal markers, are found in increased numbers in bone marrow and lung of
injured mice. Fibrocytes circulate in blood and are recruited to injured sites
via chemotactic signals. Studies with bone marrow chimeric and parabiotic mice
suggest that fibroblasts (and in some cases myofibroblasts) arise from
circulating bone marrow precursors. Chemokine and chemokine receptor interactions
are critical for the recruitment of bone marrow-derived progenitors. Once
fibrocytes arrive in injured tissues, local factors induce their differentiation
into fibroblasts/myofibroblasts. This review will summarize the experimental
findings, supporting a role for the participation of bone marrow-derived cells in
animal models of lung fibrosis, and potential implications for the pathogenesis
of fibrotic lung diseases.
PMID- 27499723
TI - Gender differences in age of smoking initiation and its association with health.
AB - BACKGROUND: It is generally accepted that smoking starts in adolescence and
earlier initiation is associated with more negative health outcomes. Some
research suggests that women initiate smoking at later ages and have more
negative health outcomes than men. The purpose of this study was to examine
gender differences in age of initiation and its association with health. METHODS:
The sample included men (n=8,506) and women (n=8,479) with a history of smoking
from the 2001-2002 National Epidemiological Survey of Alcohol Related Conditions.
Logistic regression was used to examine gender differences in the effect of late
smoking initiation on physical and mental health status after adjusting for
covariates. RESULTS: At mostly all ages after 16, women exceeded men in rates of
smoking initiation (59.8% vs. 50.3%, p<.001). Among late initiators (>=16), women
were more likely than men to have hypertension (OR:1.24,CI:1.09-1.41), heart
disease (OR:1.20,CI:1.00-1.45), major depressive disorder (OR:2.54,CI:2.22-2.92)
and generalized anxiety disorder (OR:2.34,CI:1.84-2.99). Among early initiators
(<16), women were more likely than men to have major depressive disorder
(OR:2.42,CI:2.11-2.77) and generalized anxiety disorder (OR:2.01,CI:1.59-2.54)
but there were no gender differences in the likelihood of having hypertension
(OR:1.04,CI:0.89-1.22) and heart disease (OR:1.11,CI:0.90-1.36). CONCLUSIONS: In
late adolescence and adulthood, women exceed men in smoking initiation. Late
initiation was associated with more significant physical health risks for women
than men. Our findings raise questions about generally accepted notions on the
age at which smoking initiation occurs and its association with health.
PMID- 27499724
TI - Barriers to practicing risk reduction strategies among people who inject drugs.
AB - INTRODUCTION AND AIMS: People who inject drugs (PWID) engage in practices that
put them at risk for various infections and overdose. The primary aim of this
study was to examine common barriers to engaging in two risk reduction practices
cleaning one's skin at the injection site and always using new needles to inject
- among heroin injectors in Denver, CO. METHOD: In 2010, 48 PWIDs were recruited
through street outreach and completed a structured interview that included
questions on the frequency of specific risk reduction practices (skin cleaning
and using new needles) and barriers associated with these practices. RESULTS:
Though many of the reported barriers were similar across the two practices, the
most common barriers associated with skin cleaning included being in withdrawal
and not being prepared with materials prior to injection. Fear of being arrested
and being in withdrawal were most frequently reported for using new needles.
Multivariate and t-test analyses demonstrated that individuals who skin cleaned
and used new needles more frequently reported less barriers to these practices.
CONCLUSIONS: Participants reported a number of barriers to risk reduction,
including those that are within the personal control of the injector, barriers
that are consequences of addiction or psychological problems, and those that are
structural or a function of the risk environment. Statistical analysis found that
PWIDs who were more likely to skin clean and use new needles reported less
barriers. Addressing barriers when intervening with PWID appears important to
increase the success of risk reduction interventions.
PMID- 27499725
TI - Barriers and facilitators to preventive cancer screening in Limited English
Proficient (LEP) patients: Physicians' perspectives.
AB - BACKGROUND: Limited English proficient (LEP) patients receive fewer recommended
preventive screenings than English-speaking patients. Studies have explored
patients' perceptions of the factors that contribute to this disparity, but
little research has focused on physicians' perceptions. OBJECTIVE: To describe
physicians' perceptions of the barriers and facilitators to preventive cancer
screening in LEP patients. DESIGN: Qualitative interview study using a semi
structured interview guide. PARTICIPANTS: Eight primary care physicians from
Wisconsin. APPROACH: Each interview was systematically coded to illuminate
important themes. KEY RESULTS: A variety of barriers specifically hinder LEP
patients' receipt of cancer screening, including poor language proficiency, lack
of transportation, unfamiliarity with the concept of prevention, complex
scheduling systems, poor interpretation, and limited physician time to discuss
preventive care. While physicians identified many factors that facilitate
preventive screening in general, they mentioned few that are perceived as
specific to LEP patients. CONCLUSION: We found that primary care physicians
attribute the low rates of preventive cancer screening among LEP populations to a
variety of patient, provider, interpreter, and system factors, most of which go
beyond simple language barriers. Interventions designed to reduce these barriers
and enhance the impact of identified facilitators should be multifactorial and
designed to engage primary care physicians.
PMID- 27499726
TI - Evidence mapping for decision making: feasibility versus accuracy - when to
abandon high sensitivity in electronic searches.
AB - BACKGROUND: Mapping the evidence is a relatively new methodological approach and
may be helpful for the development of research questions and decisions about
their relevance and priority. However, the amount of data available today leads
to challenges for scientists sometimes being confronted with literature searches
retrieving over 30,000 results for screening. OBJECTIVES: We conducted an
evidence mapping of the topic "diabetes and driving" to investigate its
suitability for an evidence-based national clinical guideline. In addition, we
compared a highly sensitive search with a highly specific one. METHODS: Based on
a systematic review, our database searches were limited to publications from 2002
to present in English and German language. RESULTS: Due to the strongly focused
topic and the limits, our sensitive search identified a manageable number of
references including sufficient evidence to answer our research question. Using
the specific search strategy, we achieved a reduction of citations by 25%,
concurrently identifying 88% of relevant references. CONCLUSIONS: Evidence
mapping with the intention of gaining an overview of a research field does not
require high level accuracy in contrary to systematic reviews. Keeping this
distinction in mind, a mass of extraneous information will be avoided by using
specific instead of highly sensitive search strategies.
PMID- 27499727
TI - Controlled mechanical buckling for origami-inspired construction of 3D
microstructures in advanced materials.
AB - Origami is a topic of rapidly growing interest in both the scientific and
engineering research communities due to its promising potential in a broad range
of applications. Previous assembly approaches of origami structures at the
micro/nanoscale are constrained by the applicable classes of materials,
topologies and/or capability of control over the transformation. Here, we
introduce an approach that exploits controlled mechanical buckling for autonomic
origami assembly of 3D structures across material classes from soft polymers to
brittle inorganic semiconductors, and length scales from nanometers to
centimeters. This approach relies on a spatial variation of thickness in the
initial 2D structures as an effective strategy to produce engineered folding
creases during the compressive buckling process. The elastic nature of the
assembly scheme enables active, deterministic control over intermediate states in
the 2D to 3D transformation in a continuous and reversible manner. Demonstrations
include a broad set of 3D structures formed through unidirectional,
bidirectional, and even hierarchical folding, with examples ranging from half
cylindrical columns and fish scales, to cubic boxes, pyramids, starfish, paper
fans, skew tooth structures, and to amusing system-level examples of soccer
balls, model houses, cars, and multi-floor textured buildings.
PMID- 27499728
TI - Guided Formation of 3D Helical Mesostructures by Mechanical Buckling: Analytical
Modeling and Experimental Validation.
AB - Three-dimensional (3D) helical mesostructures are attractive for applications in
a broad range of microsystem technologies, due to their mechanical and
electromagnetic properties as stretchable interconnects, radio frequency antennas
and others. Controlled compressive buckling of 2D serpentine-shaped ribbons
provides a strategy to formation of such structures in wide ranging classes of
materials (from soft polymers to brittle inorganic semiconductors) and length
scales (from nanometer to centimeter), with an ability for automated, parallel
assembly over large areas. The underlying relations between the helical
configurations and fabrication parameters require a relevant theory as the basis
of design for practical applications. Here, we present an analytic model of
compressive buckling in serpentine microstructures, based on the minimization of
total strain energy that results from various forms of spatially dependent
deformations. Experiments at micro- and millimeter-scales, together with finite
element analyses (FEA), were exploited to examine the validity of developed
model. The theoretical analyses shed light on general scaling laws in terms of
three groups of fabrication parameters (related to loading, material and 2D
geometry), including a negligible effect of material parameters and a square root
dependence of primary displacements on the compressive strain. Furthermore,
analytic solutions were obtained for the key physical quantities (e.g.,
displacement, curvature and maximum strain). A demonstrative example illustrates
how to leverage the analytic solutions in choosing the various design parameters,
such that brittle fracture or plastic yield can be avoided in the assembly
process.
PMID- 27499730
TI - Meta-Analysis of Tourette Syndrome and Attention Deficit Hyperactivity Disorder
Provides Support for a Shared Genetic Basis.
AB - Gilles de la Tourette Sydrome (TS) is a childhood onset neurodevelopmental
disorder, characterized phenotypically by the presence of multiple motor and
vocal tics. It is often accompanied by multiple psychiatric comorbidities, with
Attention Deficit/Hyperactivity Disorder (ADHD) among the most common. The
extensive co-occurrence of the two disorders suggests a shared genetic
background. A major step toward the elucidation of the genetic architecture of TS
was undertaken by the first TS Genome-wide Association Study (GWAS) reporting 552
SNPs that were moderately associated with TS (p < 1E-3). Similarly, initial ADHD
GWAS attempts and meta-analysis were not able to produce genome-wide significant
findings, but have provided insight to the genetic basis of the disorder. Here,
we examine the common genetic background of the two neuropsychiatric phenotypes,
by meta-analyzing the 552 top hits in the TS GWAS with the results of ADHD first
GWASs. We identify 19 significant SNPs, with the top four implicated genes being
TBC1D7, GUCY1A3, RAP1GDS1, and CHST11. TBCD17 harbors the top scoring SNP,
rs1866863 (p:3.23E-07), located in a regulatory region downstream of the gene,
and the third best-scoring SNP, rs2458304 (p:2.54E-06), located within an intron
of the gene. Both variants were in linkage disequilibrium with eQTL rs499818,
indicating a role in the expression levels of the gene. TBC1D7 is the third
subunit of the TSC1/TSC2 complex, an inhibitor of the mTOR signaling pathway,
with a central role in cell growth and autophagy. The top genes implicated by our
study indicate a complex and intricate interplay between them, warranting further
investigation into a possibly shared etiological mechanism for TS and ADHD.
PMID- 27499729
TI - Cyclic ADP-Ribose and Heat Regulate Oxytocin Release via CD38 and TRPM2 in the
Hypothalamus during Social or Psychological Stress in Mice.
AB - Hypothalamic oxytocin (OT) is released into the brain by cyclic ADP-ribose
(cADPR) with or without depolarizing stimulation. Previously, we showed that the
intracellular free calcium concentration ([Ca(2+)]i) that seems to trigger OT
release can be elevated by beta-NAD(+), cADPR, and ADP in mouse oxytocinergic
neurons. As these beta-NAD(+) metabolites activate warm-sensitive TRPM2 cation
channels, when the incubation temperature is increased, the [Ca(2+)]i in
hypothalamic neurons is elevated. However, it has not been determined whether OT
release is facilitated by heat in vitro or hyperthermia in vivo in combination
with cADPR. Furthermore, it has not been examined whether CD38 and TRPM2 exert
their functions on OT release during stress or stress-induced hyperthermia in
relation to the anxiolytic roles and social behaviors of OT under stress
conditions. Here, we report that OT release from the isolated hypothalami of male
mice in culture was enhanced by extracellular application of cADPR or increasing
the incubation temperature from 35 degrees C to 38.5 degrees C, and simultaneous
stimulation showed a greater effect. This release was inhibited by a cADPR
dependent ryanodine receptor inhibitor and a nonspecific TRPM2 inhibitor. The
facilitated release by heat and cADPR was suppressed in the hypothalamus isolated
from CD38 knockout mice and CD38- or TRPM2-knockdown mice. In the course of these
experiments, we noted that OT release differed markedly between individual mice
under stress with group housing. That is, when male mice received cage-switch
stress and eliminated due to their social subclass, significantly higher levels
of OT release were found in subordinates compared with ordinates. In mice exposed
to anxiety stress in an open field, the cerebrospinal fluid (CSF) OT level
increased transiently at 5 min after exposure, and the rectal temperature also
increased from 36.6 degrees C to 37.8 degrees C. OT levels in the CSF of mice
with lipopolysaccharide-induced fever (+0.8 degrees C) were higher than those of
control mice. The TRPM2 mRNA levels and immunoreactivities increased in the
subordinate group with cage-switch stress. These results showed that cADPR/CD38
and heat/TRPM2 are co-regulators of OT secretion and suggested that CD38 and
TRPM2 are potential therapeutic targets for OT release in psychiatric diseases
caused by social stress.
PMID- 27499731
TI - Zebra Finches As a Model Species to Understand the Roots of Rhythm.
PMID- 27499733
TI - Noninvasive Focused Ultrasound Stimulation Can Modulate Phase-Amplitude Coupling
between Neuronal Oscillations in the Rat Hippocampus.
AB - Noninvasive focused ultrasound stimulation (FUS) can be used to modulate neural
activity with high spatial resolution. Phase-amplitude coupling (PAC) between
neuronal oscillations is tightly associated with cognitive processes, including
learning, attention, and memory. In this study, we investigated the effect of FUS
on PAC between neuronal oscillations and established the relationship between the
PAC index and ultrasonic intensity. The rat hippocampus was stimulated using
focused ultrasound at different spatial-average pulse-average ultrasonic
intensities (3.9, 9.6, and 19.2 W/cm(2)). The local field potentials (LFPs) in
the rat hippocampus were recorded before and after FUS. Then, we analyzed PAC
between neuronal oscillations using a PAC calculation algorithm. Our results
showed that FUS significantly modulated PAC between the theta (4-8 Hz) and gamma
(30-80 Hz) bands and between the alpha (9-13 Hz) and ripple (81-200 Hz) bands in
the rat hippocampus, and PAC increased with incremental increases in ultrasonic
intensity.
PMID- 27499732
TI - The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates
in Parents of Individuals with Autism Spectrum Disorders.
AB - Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an
early-onset and a strong genetic component in their pathogenesis. According to
genetic and epidemiological data, ASD relatives present personality traits
similar to, but not as severe as the defining features of ASD, which have been
indicated as the "Broader Autism Phenotype" (BAP). BAP features seem to be more
prevalent in first-degree relatives of individuals with ASD than in the general
population. Characterizing brain profiles of relatives of autistic probands may
help to understand ASD endophenotype. The aim of this review was to provide an up
to-date overview of research findings on the neurostructural and neurofunctional
substrates in parents of individuals with ASD (pASD). The primary hypothesis was
that, like for the behavioral profile, the pASD express an intermediate
neurobiological pattern between ASD individuals and healthy controls. The 13
reviewed studies evaluated structural magnetic resonance imaging (MRI) brain
volumes, chemical signals using magnetic resonance spectroscopy (MRS), task
related functional activation by functional magnetic resonance imaging (fMRI),
electroencephalography (EEG), or magnetoencephalography (MEG) in pASD.The studies
showed that pASD are generally different from healthy controls at a structural
and functional level despite often not behaviorally impaired. More atypicalities
in neural patterns of pASD seem to be associated with higher scores at BAP
assessment. Some of the observed atypicalities are the same of the ASD probands.
In addition, the pattern of neural correlates in pASD resembles that of adult
individuals with ASD, or it is specific, possibly due to a compensatory
mechanism. Future studies should ideally include a group of pASD and HC with
their ASD and non-ASD probands respectively. They should subgrouping the pASD
according to the BAP scores, considering gender as a possible confounding factor,
and correlating these scores to underlying brain structure and function. These
types of studies may help to understand the genetic mechanisms involved in the
various clinical dimension of ASD.
PMID- 27499734
TI - The Mechanism of Regulated Release of Lasso/Teneurin-2.
AB - Teneurins are large cell-surface receptors involved in axon guidance. Teneurin-2
(also known as latrophilin-1-associated synaptic surface organizer (Lasso))
interacts across the synaptic cleft with presynaptic latrophilin-1, an adhesion G
protein-coupled receptor that participates in regulating neurotransmitter
release. Lasso-latrophilin-1 interaction mediates synapse formation and calcium
signaling, highlighting the important role of this trans-synaptic receptor pair.
However, Lasso is thought to be proteolytically cleaved within its ectodomain and
released into the medium, making it unclear whether it acts as a proper cell
surface receptor or a soluble protein. We demonstrate here that during its
intracellular processing Lasso is constitutively cleaved at a furin site within
its ectodomain. The cleaved fragment, which encompasses almost the entire
ectodomain of Lasso, is potentially soluble; however, it remains anchored on the
cell surface via its non-covalent interaction with the transmembrane fragment of
Lasso. Lasso is also constitutively cleaved within the intracellular domain
(ICD). Finally, Lasso can be further proteolytically cleaved within the
transmembrane domain. The third cleavage is regulated and releases the entire
ectodomain of Lasso into the medium. The released ectodomain of Lasso retains its
functional properties and binds latrophilin-1 expressed on other cells; this
binding stimulates intracellular Ca(2+) signaling in the target cells. Thus,
Lasso not only serves as a bona fide cell-surface receptor, but also as a
partially released target-derived signaling factor.
PMID- 27499735
TI - Adaptation of Saccadic Sequences with and without Remapping.
AB - It is relatively easy to adapt visually-guided saccades because the visual vector
and the saccade vector match. The retinal error at the saccade landing position
is compared to the prediction error, based on target location and efference copy.
If these errors do not match, planning processes at the level(s) of the visual
and/or motor vector processing are assumed to be inaccurate and the saccadic
response is adjusted. In the case of a sequence of two saccades, the final error
can be attributed to the last saccade vector or to the entire saccadic
displacement. Here, we asked whether and how adaptation can occur in the case of
remapped saccades, such as during the classic double-step saccade paradigm, where
the visual and motor vectors of the second saccade do not coincide and so the
attribution of error is ambiguous. Participants performed saccades sequences to
two targets briefly presented prior to first saccade onset. The second saccade
target was either briefly re-illuminated (sequential visually-guided task) or not
(remapping task) upon first saccade offset. To drive adaptation, the second
target was presented at a displaced location (backward or forward jump condition
or control-no jump) at the end of the second saccade. Pre- and post-adaptation
trials were identical, without the re-appearance of the target after the second
saccade. For the 1st saccade endpoints, there was no change as a function of
adaptation. For the 2nd saccade, there was a similar increase in gain in the
forward jump condition (52% and 61% of target jump) in the two tasks, whereas the
gain decrease in the backward condition was much smaller for the remapping task
than for the sequential visually-guided task (41% vs. 94%). In other words, the
absolute gain change was similar between backward and forward adaptation for
remapped saccades. In conclusion, we show that remapped saccades can be adapted,
suggesting that the error is attributed to the visuo-motor transformation of the
remapped visual vector. The mechanisms by which adaptation takes place for
remapped saccades may be similar to those of forward sequential visually-guided
saccades, unlike those involved in adaptation for backward sequential visually
guided saccades.
PMID- 27499736
TI - Amplitude of Sensorimotor Mu Rhythm Is Correlated with BOLD from Multiple Brain
Regions: A Simultaneous EEG-fMRI Study.
AB - The mu rhythm is a field oscillation in the ~10Hz range over the sensorimotor
cortex. For decades, the suppression of mu (event-related desynchronization) has
been used to index movement planning, execution, and imagery. Recent work reports
that non-motor processes, such as spatial attention and movement observation,
also desynchronize mu, raising the possibility that the mu rhythm is associated
with the activity of multiple brain regions and systems. In this study, we tested
this hypothesis by recording simultaneous resting-state EEG-fMRI from healthy
subjects. Independent component analysis (ICA) was applied to extract the mu
components. The amplitude (power) fluctuations of mu were estimated as a time
series using a moving-window approach, which, after convolving with a canonical
hemodynamic response function (HRF), was correlated with blood-oxygen-level
dependent (BOLD) signals from the entire brain. Two main results were found.
First, mu power was negatively correlated with BOLD from areas of the
sensorimotor network, the attention control network, the putative mirror neuron
system, and the network thought to support theory of mind. Second, mu power was
positively correlated with BOLD from areas of the salience network, including
anterior cingulate cortex and anterior insula. These results are consistent with
the hypothesis that sensorimotor mu rhythm is associated with multiple brain
regions and systems. They also suggest that caution should be exercised when
attempting to interpret mu modulation in terms of a single brain network.
PMID- 27499737
TI - Short-Term Plasticity in a Monosynaptic Reflex Pathway to Forearm Muscles after
Continuous Robot-Assisted Passive Stepping.
AB - Both active and passive rhythmic limb movements reduce the amplitude of spinal
cord Hoffmann (H-) reflexes in muscles of moving and distant limbs. This could
have clinical utility in remote modulation of the pathologically hyperactive
reflexes found in spasticity after stroke or spinal cord injury. However, such
clinical translation is currently hampered by a lack of critical information
regarding the minimum or effective duration of passive movement needed for
modulating spinal cord excitability. We therefore investigated the H-reflex
modulation in the flexor carpi radialis (FCR) muscle during and after various
durations (5, 10, 15, and 30 min) of passive stepping in 11 neurologically normal
subjects. Passive stepping was performed by a robotic gait trainer system
(Lokomat((r))) while a single pulse of electrical stimulation to the median nerve
elicited H-reflexes in the FCR. The amplitude of the FCR H-reflex was
significantly suppressed during passive stepping. Although 30 min of passive
stepping was sufficient to elicit a persistent H-reflex suppression that lasted
up to 15 min, 5 min of passive stepping was not. The duration of H-reflex
suppression correlated with that of the stepping. These findings suggest that the
accumulation of stepping-related afferent feedback from the leg plays a role in
generating short-term interlimb plasticity in the circuitry of the FCR H-reflex.
PMID- 27499739
TI - Retraction: Revisiting hydrocephalus as a model to study brain resilience.
AB - [This retracts the article on p. 181 in vol. 5, PMID: 22232589.].
PMID- 27499738
TI - Temporal Dynamics of the Default Mode Network Characterize Meditation-Induced
Alterations in Consciousness.
AB - Current research suggests that human consciousness is associated with complex,
synchronous interactions between multiple cortical networks. In particular, the
default mode network (DMN) of the resting brain is thought to be altered by
changes in consciousness, including the meditative state. However, it remains
unclear how meditation alters the fast and ever-changing dynamics of brain
activity within this network. Here we addressed this question using simultaneous
electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to
compare the spatial extents and temporal dynamics of the DMN during rest and
meditation. Using fMRI, we identified key reductions in the posterior cingulate
hub of the DMN, along with increases in right frontal and left temporal areas, in
experienced meditators during rest and during meditation, in comparison to
healthy controls (HCs). We employed the simultaneously recorded EEG data to
identify the topographical microstate corresponding to activation of the DMN.
Analysis of the temporal dynamics of this microstate revealed that the average
duration and frequency of occurrence of DMN microstate was higher in meditators
compared to HCs. Both these temporal parameters increased during meditation,
reflecting the state effect of meditation. In particular, we found that the
alteration in the duration of the DMN microstate when meditators entered the
meditative state correlated negatively with their years of meditation experience.
This reflected a trait effect of meditation, highlighting its role in producing
durable changes in temporal dynamics of the DMN. Taken together, these findings
shed new light on short and long-term consequences of meditation practice on this
key brain network.
PMID- 27499740
TI - Effects of Calcium Spikes in the Layer 5 Pyramidal Neuron on Coincidence
Detection and Activity Propagation.
AB - The role of dendritic spiking mechanisms in neural processing is so far poorly
understood. To investigate the role of calcium spikes in the functional
properties of the single neuron and recurrent networks, we investigated a three
compartment neuron model of the layer 5 pyramidal neuron with calcium dynamics in
the distal compartment. By performing single neuron simulations with noisy
synaptic input and occasional large coincident input at either just the distal
compartment or at both somatic and distal compartments, we show that the presence
of calcium spikes confers a substantial advantage for coincidence detection in
the former case and a lesser advantage in the latter. We further show that the
experimentally observed critical frequency phenomenon, in which action potentials
triggered by stimuli near the soma above a certain frequency trigger a calcium
spike at distal dendrites, leading to further somatic depolarization, is not
exhibited by a neuron receiving realistically noisy synaptic input, and so is
unlikely to be a necessary component of coincidence detection. We next
investigate the effect of calcium spikes in propagation of spiking activities in
a feed-forward network (FFN) embedded in a balanced recurrent network. The
excitatory neurons in the network are again connected to either just the distal,
or both somatic and distal compartments. With purely distal connectivity,
activity propagation is stable and distinguishable for a large range of recurrent
synaptic strengths if the feed-forward connections are sufficiently strong, but
propagation does not occur in the absence of calcium spikes. When connections are
made to both the somatic and the distal compartments, activity propagation is
achieved for neurons with active calcium dynamics at a much smaller number of
neurons per pool, compared to a network of passive neurons, but quickly becomes
unstable as the strength of recurrent synapses increases. Activity propagation at
higher scaling factors can be stabilized by increasing network inhibition or
introducing short term depression in the excitatory synapses, but the signal to
noise ratio remains low. Our results demonstrate that the interaction of
synchrony with dendritic spiking mechanisms can have profound consequences for
the dynamics on the single neuron and network level.
PMID- 27499741
TI - CoSMoMVPA: Multi-Modal Multivariate Pattern Analysis of Neuroimaging Data in
Matlab/GNU Octave.
AB - Recent years have seen an increase in the popularity of multivariate pattern
(MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much
lesser extent, magneto- and electro-encephalography (M/EEG) data. We present
CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the
intersection of the Matlab and GNU Octave languages, that treats both fMRI and
M/EEG data as first-class citizens. CoSMoMVPA supports all state-of-the-art MVP
analysis techniques, including searchlight analyses, classification,
correlations, representational similarity analysis, and the time generalization
method. These can be used to address both data-driven and hypothesis-driven
questions about neural organization and representations, both within and across:
space, time, frequency bands, neuroimaging modalities, individuals, and species.
It uses a uniform data representation of fMRI data in the volume or on the
surface, and of M/EEG data at the sensor and source level. Through various
external toolboxes, it directly supports reading and writing a variety of fMRI
and M/EEG neuroimaging formats, and, where applicable, can convert between them.
As a result, it can be integrated readily in existing pipelines and used with
existing preprocessed datasets. CoSMoMVPA overloads the traditional volumetric
searchlight concept to support neighborhoods for M/EEG and surface-based fMRI
data, which supports localization of multivariate effects of interest across
space, time, and frequency dimensions. CoSMoMVPA also provides a generalized
approach to multiple comparison correction across these dimensions using
Threshold-Free Cluster Enhancement with state-of-the-art clustering and
permutation techniques. CoSMoMVPA is highly modular and uses abstractions to
provide a uniform interface for a variety of MVP measures. Typical analyses
require a few lines of code, making it accessible to beginner users. At the same
time, expert programmers can easily extend its functionality. CoSMoMVPA comes
with extensive documentation, including a variety of runnable demonstration
scripts and analysis exercises (with example data and solutions). It uses best
software engineering practices including version control, distributed
development, an automated test suite, and continuous integration testing. It can
be used with the proprietary Matlab and the free GNU Octave software, and it
complies with open source distribution platforms such as NeuroDebian. CoSMoMVPA
is Free/Open Source Software under the permissive MIT license. Website:
http://cosmomvpa.org Source code: https://github.com/CoSMoMVPA/CoSMoMVPA.
PMID- 27499742
TI - Control of Transmembrane Protein Diffusion within the Postsynaptic Density
Assessed by Simultaneous Single-Molecule Tracking and Localization Microscopy.
AB - Postsynaptic transmembrane proteins are critical elements of synapses, mediating
trans-cellular contact, sensitivity to neurotransmitters and other signaling
molecules, and flux of Ca and other ions. Positioning and mobility of each member
of this large class of proteins is critical to their individual function at the
synapse. One critical example is that the position of glutamate receptors within
the postsynaptic density (PSD) strongly modulates their function by aligning or
misaligning them with sites of presynaptic vesicle fusion. In addition, the
regulated ability of receptors to move in or out of the synapse is critical for
activity-dependent plasticity. However, factors that control receptor mobility
within the boundaries of the synapse are not well understood. Notably, PSD
scaffold molecules accumulate in domains much smaller than the synapse. Within
these nanodomains, the density of proteins is considerably higher than that of
the synapse as a whole, so high that steric hindrance is expected to reduce
receptor mobility substantially. However, while numerical modeling has
demonstrated several features of how the varying protein density across the face
of a single PSD may modulate receptor motion, there is little experimental
information about the extent of this influence. To address this critical aspect
of synaptic organizational dynamics, we performed single-molecule tracking of
transmembrane proteins using universal point accumulation-for-imaging-in
nanoscale-topography (uPAINT) over PSDs whose internal structure was
simultaneously resolved using photoactivated localization microscopy (PALM). The
results provide important experimental confirmation that PSD scaffold protein
density strongly influences the mobility of transmembrane proteins. A protein
with a cytosolic domain that does not bind PSD-95 was still slowed in regions of
high PSD-95 density, suggesting that crowding by scaffold molecules and perhaps
other proteins is sufficient to stabilize receptors even in the absence of
binding. Because numerous proteins thought to be involved in establishing PSD
structure are linked to disorders including autism and depression, this motivates
further exploration of how PSD nanostructure is created. The combined application
PALM and uPAINT should be invaluable for distinguishing the interactions of
mobile proteins with their nano-environment both in synapses and other cellular
compartments.
PMID- 27499743
TI - Visceral Hypersensitivity Is Provoked by 2,4,6-Trinitrobenzene Sulfonic Acid
Induced Ileitis in Rats.
AB - BACKGROUND AND AIMS: Crohn's Disease (CD), a chronic Inflammatory Bowel Disease,
can occur in any part of the gastrointestinal tract, but most frequently in the
ileum. Visceral hypersensitivity contributes for development of chronic abdominal
pain in this disease. Currently, the understanding of the mechanism underlying
hypersensitivity of Crohn's ileitis has been hindered by a lack of specific
animal model. The present study is undertaken to investigate the visceral
hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced
ileitis rats. METHODS: Male Sprague-Dawley rats were anaesthetized and
laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in
30% ethanol, n = 48), an equal volume of 30% Ethanol (n = 24), and Saline (n =
24), respectively. Visceral hypersensitivity was assessed by visceromotor
responses (VMR) to 20, 40, 60, 80, and 100 mmHg colorectal distension pressure
(CRD) at day 1, 3, 7, 14, 21, and 28. Immediately after CRD test, the rats were
euthanized for collecting the terminal ileal segment for histopathological
examinations and ELISA of myleoperoxidase and cytokines (TNF-alpha, IL-1beta, IL
6), and dorsal root ganglia (T11) for determination of calcitonin gene-related
peptide by immunohistochemistry, respectively. RESULTS: Among all groups, TNBS
treatment showed transmural inflammation initially at 3 days, reached maximum at
7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05)
VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive
positive cells increased (P < 0.05) in dorsal root ganglia at day 7 to 21, which
was persistently consistent with visceral hypersensitivity in TNBS-treated rats.
CONCLUSION: TNBS injection into the ileum induced transmural ileitis including
granuloma and visceral hypersensitivity. As this model mimics clinical
manifestations of CD, it may provide a road map to probe the pathogenesis of gut
inflammation and visceral hypersensitivity, as well as for establishing the
therapeutic protocol for Crohn's ileitis.
PMID- 27499744
TI - Using Multigroup-Multiphase Latent State-Trait Models to Study Treatment-Induced
Changes in Intra-Individual State Variability: An Application to Smokers' Affect.
AB - Sometimes, researchers are interested in whether an intervention, experimental
manipulation, or other treatment causes changes in intra-individual state
variability. The authors show how multigroup-multiphase latent state-trait (MG-MP
LST) models can be used to examine treatment effects with regard to both mean
differences and differences in state variability. The approach is illustrated
based on a randomized controlled trial in which N = 338 smokers were randomly
assigned to nicotine replacement therapy (NRT) vs. placebo prior to quitting
smoking. We found that post quitting, smokers in both the NRT and placebo group
had significantly reduced intra-individual affect state variability with respect
to the affect items calm and content relative to the pre-quitting phase. This
reduction in state variability did not differ between the NRT and placebo groups,
indicating that quitting smoking may lead to a stabilization of individuals'
affect states regardless of whether or not individuals receive NRT.
PMID- 27499745
TI - Incubation and Intuition in Creative Problem Solving.
AB - Creative problem solving, in which novel solutions are required, has often been
seen as involving a special role for unconscious processes (Unconscious Work)
which can lead to sudden intuitive solutions (insights) when a problem is set
aside during incubation periods. This notion of Unconscious Work during
incubation periods is supported by a review of experimental studies and
particularly by studies using the Immediate Incubation paradigm. Other
explanations for incubation effects, in terms of Intermittent Work or Beneficial
Forgetting are considered. Some recent studies of divergent thinking, using the
Alternative Uses task, carried out in my laboratory regarding Immediate vs.
Delayed Incubation and the effects of resource competition from interpolated
activities are discussed. These studies supported a role for Unconscious Work as
against Intermittent Conscious work or Beneficial Forgetting in incubation.
PMID- 27499746
TI - Aldo-Keto Reductases 1B in Adrenal Cortex Physiology.
AB - Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo
keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups
from a wide variety of substrates, such as aliphatic and aromatic aldehydes or
ketones. Due to the involvement of human aldose reductases in pathologies, such
as diabetic complications and cancer, AKR1B subgroup enzymatic properties have
been extensively characterized. However, the issue of AKR1B function in non
pathologic conditions remains poorly resolved. Adrenal activities generated large
amount of harmful aldehydes from lipid peroxidation and steroidogenesis,
including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which
can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have
been shown to be endowed with prostaglandin F synthase (PGFS) activity,
suggesting that, in addition to possible scavenger function, they could instigate
paracrine signals. Interestingly, the adrenal gland is one of the major sites for
human and murine AKR1B expression, suggesting that their detoxifying/signaling
activity could be specifically required for the correct handling of adrenal
function. Moreover, chronic effects of ACTH result in a coordinated regulation of
genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review
presents the molecular mechanisms accounting for the adrenal-specific expression
of some AKR1B genes. Using data from recent mouse genetic models, we will try to
connect their enzymatic properties and regulation with adrenal functions.
PMID- 27499747
TI - Functional Characterization of a Hexose Transporter from Root Endophyte
Piriformospora indica.
AB - Understanding the mechanism of photosynthate transfer at symbiotic interface by
fungal monosaccharide transporter is of substantial importance. The carbohydrate
uptake at the apoplast by the fungus is facilitated by PiHXT5 hexose transporter
in root endophytic fungus Piriformospora indica. The putative PiHXT5 belongs to
MFS superfamily with 12 predicted transmembrane helices. It possess sugar
transporter PFAM motif (PF0083) and MFS superfamily domain (PS50850). It contains
the signature tags related to glucose transporter GLUT1 of human erythrocyte.
PiHXT5 is regulated in response to mutualism as well as glucose concentration. We
have functionally characterized PiHXT5 by complementation of hxt-null mutant of
Saccharomyces cerevisiae EBY.VW4000. It is involved in transport of multiple
sugars ranging from D-glucose, D-fructose, D-xylose, D-mannose, D-galactose with
decreasing affinity. The uncoupling experiments indicate that it functions as
H(+)/glucose co-transporter. Further, pH dependence analysis suggests that it
functions maximum between pH 5 and 6. The expression of PiHXT5 is dependent on
glucose concentration and was found to be expressed at low glucose levels (1 mM)
which indicate its role as a high affinity glucose transporter. Our study on this
sugar transporter will help in better understanding of carbon metabolism and flow
in this agro-friendly fungus.
PMID- 27499748
TI - Serological Evidence of Immune Priming by Group A Streptococci in Patients with
Acute Rheumatic Fever.
AB - Acute rheumatic fever (ARF) is an autoimmune response to Group A Streptococcus
(GAS) infection. Repeated GAS exposures are proposed to 'prime' the immune system
for autoimmunity. This notion of immune-priming by multiple GAS infections was
first postulated in the 1960s, but direct experimental evidence to support the
hypothesis has been lacking. Here, we present novel methodology, based on
antibody responses to GAS T-antigens, that enables previous GAS exposures to be
mapped in patient sera. T-antigens are surface expressed, type specific antigens
and GAS strains fall into 18 major clades or T-types. A panel of recombinant T
antigens was generated and immunoassays were performed in parallel with serum
depletion experiments allowing type-specific T-antigen antibodies to be
distinguished from cross-reactive antibodies. At least two distinct GAS exposures
were detected in each of the ARF sera tested. Furthermore, no two sera had the
same T-antigen reactivity profile suggesting that each patient was exposed to a
unique series of GAS T-types prior to developing ARF. The methods have provided
much-needed experimental evidence to substantiate the immune-priming hypothesis,
and will facilitate further serological profiling studies that explore the
multifaceted interactions between GAS and the host.
PMID- 27499749
TI - Hospital Effluents Are One of Several Sources of Metal, Antibiotic Resistance
Genes, and Bacterial Markers Disseminated in Sub-Saharan Urban Rivers.
AB - Data concerning the occurrence of emerging biological contaminants such as
antibiotic resistance genes (ARGs) and fecal indicator bacteria (FIB) in aquatic
environments in Sub-Saharan African countries is limited. On the other hand,
antibiotic resistance remains a worldwide problem which may pose serious
potential risks to human and animal health. Consequently, there is a growing
number of reports concerning the prevalence and dissemination of these
contaminants into various environmental compartments. Sediments provide the
opportunity to reconstruct the pollution history and evaluate impacts so this
study investigates the abundance and distribution of toxic metals, FIB, and ARGs
released from hospital effluent wastewaters and their presence in river sediments
receiving systems. ARGs (bla TEM, bla CTX-M, bla SHV, and aadA), total bacterial
load, and selected bacterial species FIB [Escherichia coli, Enterococcus (ENT)]
and species (Psd) were quantified by targeting species specific genes using
quantitative PCR (qPCR) in total DNA extracted from the sediments recovered from
4 hospital outlet pipes (HOP) and their river receiving systems in the City of
Kinshasa in the Democratic Republic of the Congo. The results highlight the great
concentration of toxic metals in HOP, reaching the values (in mg kg(-1)) of 47.9
(Cr), 213.6 (Cu), 1434.4 (Zn), 2.6 (Cd), 281.5 (Pb), and 13.6 (Hg). The results
also highlight the highest (P < 0.05) values of 16S rRNA, FIB, and ARGs copy
numbers in all sampling sites including upstream (control site), discharge point,
and downstream of receiving rivers, indicating that the hospital effluent water
is not an exclusive source of the biological contaminants entering the urban
rivers. Significant correlation were observed between (i) all analyzed ARGs and
total bacterial load (16S rRNA) 0.51 to 0.72 (p < 0.001, n = 65); (ii) ARGs
(except bla TEM) and FIB and Psd 0.57 < r < 0.82 (p < 0.001, n = 65); and (iii)
ARGs (except bla TEM) and toxic metals (Cd, Cr, Cu, and Zn) 0.44 to 0.72, (p <
0.001, n = 65). These findings demonstrate that several sources including
hospital and urban wastewaters contribute to the spread of toxic metals and
biological emerging contaminants in aquatic ecosystems.
PMID- 27499750
TI - Strong Inference in Mathematical Modeling: A Method for Robust Science in the
Twenty-First Century.
AB - While there are many opinions on what mathematical modeling in biology is, in
essence, modeling is a mathematical tool, like a microscope, which allows
consequences to logically follow from a set of assumptions. Only when this tool
is applied appropriately, as microscope is used to look at small items, it may
allow to understand importance of specific mechanisms/assumptions in biological
processes. Mathematical modeling can be less useful or even misleading if used
inappropriately, for example, when a microscope is used to study stars. According
to some philosophers (Oreskes et al., 1994), the best use of mathematical models
is not when a model is used to confirm a hypothesis but rather when a model shows
inconsistency of the model (defined by a specific set of assumptions) and data.
Following the principle of strong inference for experimental sciences proposed by
Platt (1964), I suggest "strong inference in mathematical modeling" as an
effective and robust way of using mathematical modeling to understand mechanisms
driving dynamics of biological systems. The major steps of strong inference in
mathematical modeling are (1) to develop multiple alternative models for the
phenomenon in question; (2) to compare the models with available experimental
data and to determine which of the models are not consistent with the data; (3)
to determine reasons why rejected models failed to explain the data, and (4) to
suggest experiments which would allow to discriminate between remaining
alternative models. The use of strong inference is likely to provide better
robustness of predictions of mathematical models and it should be strongly
encouraged in mathematical modeling-based publications in the Twenty-First
century.
PMID- 27499751
TI - Evolution and Diversity of Listeria monocytogenes from Clinical and Food Samples
in Shanghai, China.
AB - Listeria monocytogenes is a significant foodborne pathogen causing severe
systemic infections in humans with high mortality rates. The objectives of this
work were to establish a phylogenetic framework of L. monocytogenes from China
and to investigate sequence diversity among different serotypes. We selected 17
L. monocytogenes strains recovered from patients and foods in China representing
serotypes 1/2a, 1/2b, and 1/2c. Draft genome sequences were determined using
Illumina MiSeq technique and associated protocols. Open reading frames were
assigned using prokaryotic genome annotation pipeline by NCBI. Twenty-four
published genomes were included for comparative genomic and phylogenetic
analysis. More than 154,000 single nucleotide polymorphisms (SNPs) were
identified from multiple genome alignment and used to reconstruct maximum
likelihood phylogenetic tree. The 41 genomes were differentiated into lineages I
and II, which consisted of 4 and 11 subgroups, respectively. A clinical strain
from China (SHL009) contained significant SNP differences compared to the rest
genomes, whereas clinical strain SHL001 shared most recent common ancestor with
strain SHL017 from food. Moreover, clinical strains SHL004 and SHL015 clustered
together with two strains (08-5578 and 08-5923) recovered from an outbreak in
Canada. Partial sequences of a plasmid found in the Canadian strain were also
present in SHL004. We investigated the presence of various genes and gene
clusters associated with virulence and subgroup-specific genes, including
internalins, L. monocytogenes pathogenicity islands (LIPIs), L. monocytogenes
genomic islands (LGIs), stress survival islet 1 (SSI-1), and clustered regularly
interspaced short palindromic repeats (CRISPR)/cas system. A novel genomic
island, denoted as LGI-2 was identified. Comparative sequence analysis revealed
differences among the L. monocytogenes strains related to virulence, survival
abilities, and attributes against foreign genetic elements. L. monocytogenes from
China were genetically diverse. Strains from clinical specimens and food related
closely suggesting foodborne transmission of human listeriosis.
PMID- 27499753
TI - Cold Shock Proteins: A Minireview with Special Emphasis on Csp-family of
Enteropathogenic Yersinia.
AB - Bacteria have evolved a number of mechanisms for coping with stress and adapting
to changing environmental conditions. Many bacteria produce small cold shock
proteins (Csp) as a response to rapid temperature downshift (cold shock). During
cold shock, the cell membrane fluidity and enzyme activity decrease, and the
efficiency of transcription and translation is reduced due to stabilization of
nucleic acid secondary structures. Moreover, protein folding is inefficient and
ribosome function is hampered. Csps are thought to counteract these harmful
effects by serving as nucleic acid chaperons that may prevent the formation of
secondary structures in mRNA at low temperature and thus facilitate the
initiation of translation. However, some Csps are non-cold inducible and they are
reported to be involved in various cellular processes to promote normal growth
and stress adaptation responses. Csps have been shown to contribute to osmotic,
oxidative, starvation, pH and ethanol stress tolerance as well as to host cell
invasion. Therefore, Csps seem to have a wider role in stress tolerance of
bacteria than previously assumed. Yersinia enterocolitica and Yersinia
pseudotuberculosis are enteropathogens that can spread through foodstuffs and
cause an enteric infection called yersiniosis. Enteropathogenic Yersinia are
psychrotrophs that are able to grow at temperatures close to 0 degrees C and thus
they set great challenges for the modern food industry. To be able to efficiently
control psychrotrophic Yersinia during food production and storage, it is
essential to understand the functions and roles of Csps in stress response of
enteropathogenic Yersinia.
PMID- 27499752
TI - Bacterial Diversity and Community Structure of Supragingival Plaques in Adults
with Dental Health or Caries Revealed by 16S Pyrosequencing.
AB - Dental caries has a polymicrobial etiology within the complex oral microbial
ecosystem. However, the overall diversity and structure of supragingival plaque
microbiota in adult dental health and caries are not well understood. Here, 160
supragingival plaque samples from patients with dental health and different
severities of dental caries were collected for bacterial genomic DNA extraction,
pyrosequencing by amplification of the 16S rDNA V1-V3 hypervariable regions, and
bioinformatic analysis. High-quality sequences (2,261,700) clustered into 10,365
operational taxonomic units (OTUs; 97% identity), representing 453 independent
species belonging to 122 genera, 66 families, 34 orders, 21 classes, and 12
phyla. All groups shared 7522 OTUs, indicating the presence of a core plaque
microbiome. alpha diversity analysis showed that the microbial diversity in
healthy plaques exceeded that of dental caries, with the diversity decreasing
gradually with the severity of caries. The dominant phyla of plaque microbiota
included Bacteroidetes, Actinobacteria, Proteobacteria, Firmicutes, Fusobacteria,
and TM7. The dominant genera included Capnocytophaga, Prevotella, Actinomyces,
Corynebacterium, Neisseria, Streptococcus, Rothia, and Leptotrichia. beta
diversity analysis showed that the plaque microbial community structure was
similar in all groups. Using LEfSe analysis, 25 differentially abundant taxa were
identified as potential biomarkers. Key genera (27) that potentially contributed
to the differential distributions of plaque microbiota between groups were
identified by PLS-DA analysis. Finally, co-occurrence network analysis and
function predictions were performed. Treatment strategies directed toward
modulating microbial interactions and their functional output should be further
developed.
PMID- 27499755
TI - Unveiling the Role of the Integrated Endoplasmic Reticulum Stress Response in
Leishmania Infection - Future Perspectives.
AB - The integrated endoplasmic reticulum stress response (IERSR) is an evolutionarily
conserved adaptive mechanism that ensures endoplasmic reticulum (ER) homeostasis
and cellular survival in the presence of stress including nutrient deprivation,
hypoxia, and imbalance of Ca(+) homeostasis, toxins, and microbial infection.
Three transmembrane proteins regulate integrated signaling pathways that comprise
the IERSR, namely, IRE-1 that activates XBP-1, the pancreatic ER kinase (PERK)
that phosphorylates the eukaryotic translation initiation factor 2 and
transcription factor 6 (ATF6). The roles of IRE-1, PERK, and ATF4 in viral and
some bacterial infections are well characterized. The role of IERSR in infections
by intracellular parasites is still poorly understood, although one could
anticipate that IERSR may play an important role on the host's cell response.
Recently, our group reported the important aspects of XBP-1 activation in
Leishmania amazonensis infection. It is, however, necessary to address the
relevance of the other IERSR branches, together with the possible role of IERSR
in infections by other Leishmania species, and furthermore, to pursue the
possible implications in the pathogenesis and control of parasite replication in
macrophages.
PMID- 27499754
TI - Utilization of Dimethyl Fumarate and Related Molecules for Treatment of Multiple
Sclerosis, Cancer, and Other Diseases.
AB - Several drugs have been approved for treatment of multiple sclerosis (MS).
Dimethyl fumarate (DMF) is utilized as an oral drug to treat this disease and is
proven to be potent with less side effects than several other drugs. On the other
hand, monomethyl fumarate (MMF), a related compound, has not been examined in
greater details although it has the potential as a therapeutic drug for MS and
other diseases. The mechanism of action of DMF or MMF is related to their ability
to enhance the antioxidant pathways and to inhibit reactive oxygen species.
However, other mechanisms have also been described, which include effects on
monocytes, dendritic cells, T cells, and natural killer cells. It is also
reported that DMF might be useful for treating psoriasis, asthma, aggressive
breast cancers, hematopoeitic tumors, inflammatory bowel disease, intracerebral
hemorrhage, osteoarthritis, chronic pancreatitis, and retinal ischemia. In this
article, we will touch on some of these diseases with an emphasis on the effects
of DMF and MMF on various immune cells.
PMID- 27499757
TI - Overexpression of a Modified Plant Thionin Enhances Disease Resistance to Citrus
Canker and Huanglongbing (HLB).
AB - Huanglongbing (HLB or citrus greening disease) caused by Candidatus Liberibacter
asiaticus (Las) is a great threat to the US citrus industry. There are no proven
strategies to eliminate HLB disease and no cultivar has been identified with
strong HLB resistance. Citrus canker is also an economically important disease
associated with a bacterial pathogen (Xanthomonas citri). In this study, we
characterized endogenous citrus thionins and investigated their expression in
different citrus tissues. Since no HLB-resistant citrus cultivars have been
identified, we attempted to develop citrus resistant to both HLB and citrus
canker through overexpression of a modified plant thionin. To improve
effectiveness for disease resistance, we modified and synthesized the sequence
encoding a plant thionin and cloned into the binary vector pBinPlus/ARS. The
construct was then introduced into Agrobacterium strain EHA105 for citrus
transformation. Transgenic Carrizo plants expressing the modified plant thionin
were generated by Agrobacterium-mediated transformation. Successful
transformation and transgene gene expression was confirmed by molecular analysis.
Transgenic Carrizo plants expressing the modified thionin gene were challenged
with X. citri 3213 at a range of concentrations, and a significant reduction in
canker symptoms and a decrease in bacterial growth were demonstrated compared to
nontransgenic plants. Furthermore, the transgenic citrus plants were challenged
with HLB via graft inoculation. Our results showed significant Las titer
reduction in roots of transgenic Carrizo compared with control plants and reduced
scion Las titer 12 months after graft inoculation. These data provide promise for
engineering citrus disease resistance against HLB and canker.
PMID- 27499756
TI - Identification of microRNAs and Their Target Genes Explores miRNA-Mediated
Regulatory Network of Cytoplasmic Male Sterility Occurrence during Anther
Development in Radish (Raphanus sativus L.).
AB - MicroRNAs (miRNAs) are a type of endogenous non-coding small RNAs that play
critical roles in plant growth and developmental processes. Cytoplasmic male
sterility (CMS) is typically a maternally inherited trait and widely used in
plant heterosis utilization. However, the miRNA-mediated regulatory network of
CMS occurrence during anther development remains largely unknown in radish. In
this study, a comparative small RNAome sequencing was conducted in floral buds of
CMS line 'WA' and its maintainer line 'WB' by high-throughput sequencing. A total
of 162 known miRNAs belonging to 25 conserved and 24 non-conserved miRNA families
were isolated and 27 potential novel miRNA families were identified for the first
time in floral buds of radish. Of these miRNAs, 28 known and 14 potential novel
miRNAs were differentially expressed during anther development. Several target
genes for CMS occurrence-related miRNAs encode important transcription factors
and functional proteins, which might be involved in multiple biological processes
including auxin signaling pathways, signal transduction, miRNA target silencing,
floral organ development, and organellar gene expression. Moreover, the
expression patterns of several CMS occurrence-related miRNAs and their targets
during three stages of anther development were validated by qRT-PCR. In addition,
a potential miRNA-mediated regulatory network of CMS occurrence during anther
development was firstly proposed in radish. These findings could contribute new
insights into complex miRNA-mediated genetic regulatory network of CMS occurrence
and advance our understanding of the roles of miRNAs during CMS occurrence and
microspore formation in radish and other crops.
PMID- 27499758
TI - Geography Plays a More Important Role than Soil Composition on Structuring
Genetic Variation of Pseudometallophyte Commelina communis.
AB - Pseudometallophytes are excellent models to study microevolution and local
adaptation to soil pollution, as they can grow both on metalliferous and
contrasting non-metalliferous soils. Although, there has been accumulating
evidence for the effects of edaphic conditions and geographical isolation on the
genetic structure of pesudometallophytes, it is still a difficult problem in
evolutionary biology to assess their relative importance. In this study, we
investigated the spatial patterns of genetic variability, population
differentiation and genetic groups in pseudometallophyte Commelina communis with
12 microsatellite loci. Eight metallicolous and six non-metallicolous populations
of C. communis were sampled from cupriferous sites and surrounding non
contaminated areas in China. Neither significant reduction in genetic diversity
nor apparent founder and bottleneck effects were observed in metallicolous
populations of C. communis. Based on Bayesian and Neighbor-Joining clustering
analyses and a principal coordinates analysis, all sampled populations were found
to be mainly separated into three genetic groups, corresponding well to their
geographical locations rather than edaphic origins. Moreover, a significant and
strong correlation between population genetic divergence and geographical
distance were detected by Mantel test (r = 0.33; P < 0.05) and multiple matrix
regression with randomization (MMRR; betaD = 0.57, P < 0.01). However, the effect
of copper concentration on genetic patterns of C. communis was not significant
(MMRR; betaE = -0.17, P = 0.12). Our study clearly demonstrated that the extreme
edaphic conditions in metalliferous areas had limited effects on the genetic
variability in C. communis. Geographic distance played a more important role in
affecting the genetic structure of C. communis than soil composition did. In C.
communis, the geographically disjunctive populations on metalliferous soils had
multiple origins and evolved independently from nearby non-metallicolous
populations.
PMID- 27499759
TI - A Protein-Based Genetic Screening Uncovers Mutants Involved in Phytochrome
Signaling in Arabidopsis.
AB - Plants perceive red and far-red region of the light spectrum to regulate
photomorphogenesis through a family of photoreceptors called phytochromes.
Phytochromes transduce the light signals to trigger a cascade of downstream gene
regulation in part via a subfamily of bHLH transcription factors called
Phytochrome Interacting Factors (PIFs). As the repressors of light signaling
pathways, most PIFs are phosphorylated and degraded through the ubiquitin/26S
proteasome pathway in response to light. The mechanisms involved in the
phosphorylation and degradation of PIFs have not been fully understood yet. Here
we used an EMS mutagenesis and luminescent imaging system to identify mutants
defective in the degradation of one of the PIFs, called PIF1. We identified five
mutants named stable PIF (spf) that showed reduced degradation of PIF1 under
light treatment in both luminescent imaging and immunoblot assays. The amounts of
PIF1 in spf3, spf4, and spf5 were similar to a PIF1 missense mutant (PIF1-3M)
that lacks interactions between PIF1 and phyA/phyB under light. The hypocotyl
lengths of spf1 and spf2 were slightly longer under red light compared to the LUC
PIF1 control, while only spf1 displayed weak phenotype under far-red light
conditions. Interestingly, the spf3, spf4, and spf5 displayed high abundance of
PIF1, yet the hypocotyl lengths were similar to the wild type under these
conditions. Cloning and characterization of these mutants will help identify key
players in the light signaling pathways including, the light-regulated kinase(s)
and the E3 ligase(s) necessary for the light-induced degradation of PIFs.
PMID- 27499760
TI - Changes in H(+)-ATP Synthase Activity, Proton Electrochemical Gradient, and pH in
Pea Chloroplast Can Be Connected with Variation Potential.
AB - Local stimulation induces generation and propagation of electrical signals,
including the variation potential (VP) and action potential, in plants. Burning
induced VP changes the physiological state of plants; specifically, it
inactivates photosynthesis. However, the mechanisms that decrease photosynthesis
are poorly understood. We investigated these mechanisms by measuring VP-connected
systemic changes in CO2 assimilation, parameters of light reactions of
photosynthesis, electrochromic pigment absorbance shifts, and light scattering.
We reveal that inactivation of photosynthesis in the pea, including inactivation
of dark and light reactions, was connected with the VP. Inactivation of dark
reactions decreased the rate constant of the fast relaxation of the
electrochromic pigment absorbance shift, which reflected a decrease in the H(+)
ATP synthase activity. This decrease likely contributed to the acidification of
the chloroplast lumen, which developed after VP induction. However, VP-connected
decrease of the proton motive force across the thylakoid membrane, possibly,
reflected a decreased pH in the stroma. This decrease may be another mechanism of
chloroplast lumen acidification. Overall, stroma acidification can decrease
electron flow through photosystem I, and lumen acidification induces growth of
fluorescence non-photochemical quenching and decreases electron flow through
photosystem II, i.e., pH decreases in the stroma and lumen, possibly, contribute
to the VP-induced inactivation of light reactions of photosynthesis.
PMID- 27499761
TI - Nitrogen Addition Enhances Drought Sensitivity of Young Deciduous Tree Species.
AB - Understanding how trees respond to global change drivers is central to predict
changes in forest structure and functions. Although there is evidence on the mode
of nitrogen (N) and drought (D) effects on tree growth, our understanding of the
interplay of these factors is still limited. Simultaneously, as mixtures are
expected to be less sensitive to global change as compared to monocultures, we
aimed to investigate the combined effects of N addition and D on the productivity
of three tree species (Fagus sylvatica, Quercus petraea, Pseudotsuga menziesii)
in relation to functional diverse species mixtures using data from a 4-year field
experiment in Northwest Germany. Here we show that species mixing can mitigate
the negative effects of combined N fertilization and D events, but the community
response is mainly driven by the combination of certain traits rather than the
tree species richness of a community. For beech, we found that negative effects
of D on growth rates were amplified by N fertilization (i.e., combined treatment
effects were non-additive), while for oak and fir, the simultaneous effects of N
and D were additive. Beech and oak were identified as most sensitive to combined
N+D effects with a strong size-dependency observed for beech, suggesting that the
negative impact of N+D becomes stronger with time as beech grows larger. As a
consequence, the net biodiversity effect declined at the community level, which
can be mainly assigned to a distinct loss of complementarity in beech-oak
mixtures. This pattern, however, was not evident in the other species-mixtures,
indicating that neighborhood composition (i.e., trait combination), but not tree
species richness mediated the relationship between tree diversity and treatment
effects on tree growth. Our findings point to the importance of the qualitative
role ('trait portfolio') that biodiversity play in determining resistance of
diverse tree communities to environmental changes. As such, they provide further
understanding for adaptive management strategies in the context of global change.
PMID- 27499762
TI - An Adaptive Defect Weighted Sampling Algorithm to Design Pseudoknotted RNA
Secondary Structures.
AB - Computational design of RNA sequences that fold into targeted secondary
structures has many applications in biomedicine, nanotechnology and synthetic
biology. An RNA molecule is made of different types of secondary structure
elements and an important RNA element named pseudoknot plays a key role in
stabilizing the functional form of the molecule. However, due to the
computational complexities associated with characterizing pseudoknotted RNA
structures, most of the existing RNA sequence designer algorithms generally
ignore this important structural element and therefore limit their applications.
In this paper we present a new algorithm to design RNA sequences for
pseudoknotted secondary structures. We use NUPACK as the folding algorithm to
compute the equilibrium characteristics of the pseudoknotted RNAs, and describe a
new adaptive defect weighted sampling algorithm named Enzymer to design low
ensemble defect RNA sequences for targeted secondary structures including
pseudoknots. We used a biological data set of 201 pseudoknotted structures from
the Pseudobase library to benchmark the performance of our algorithm. We compared
the quality characteristics of the RNA sequences we designed by Enzymer with the
results obtained from the state of the art MODENA and antaRNA. Our results show
our method succeeds more frequently than MODENA and antaRNA do, and generates
sequences that have lower ensemble defect, lower probability defect and higher
thermostability. Finally by using Enzymer and by constraining the design to a
naturally occurring and highly conserved Hammerhead motif, we designed 8
sequences for a pseudoknotted cis-acting Hammerhead ribozyme. Enzymer is
available for download at https://bitbucket.org/casraz/enzymer.
PMID- 27499763
TI - Body mass index in girls with idiopathic central precocious puberty during and
after treatment with GnRH analogues.
AB - BACKGROUND: In girls with Idiopathic Central Precocious Puberty (ICPP) concern
has been raised by the potential impact of GnRH-analogues (GnRHa) treatment on
body weight. We evaluated the effect of GnRHa on Body Mass Index (BMI) in girls
with ICPP according to weight status at diagnosis. METHODS: One hundred seventeen
ICPP girls were divided according to pretreatment weight status in: normal weight
(NW), overweight (OW) and obese (OB). BMI at one and two years of treatment was
assessed. BMI-SDS of 60 patients who reached adult height (AH) was compared to
that of 33 ICPP untreated girls. RESULTS: NW girls significantly increased their
baseline BMI-SDS at 1 and 2 years of treatment. OW girls only had a significant
increment at one year of treatment while OB girls showed no BMI-SDS change.
Patients evaluated at AH (at least four years after GnRHa withdrawal) showed a
significant decrease on BMI compared to baseline and a significantly lower BMI
than the untreated group. CONCLUSION: In ICPP girls the BMI increase under GnRHa
was inversely related to the pretreatment weight status. In the long term follow
up, no detrimental effect of GnRHa on body weight was observed. BMI-SDS was lower
in treated than in untreated girls.
PMID- 27499764
TI - Reproducibility of serum IgE, Ara h2 skin prick testing and fraction of exhaled
nitric oxide for predicting clinical peanut allergy in children.
AB - BACKGROUND: Ara h2 sIgE serum levels improve the diagnostic accuracy for
predicting peanut allergy, but the use of Ara h2 purified protein as a skin prick
test (SPT), has not been substantially evaluated. The fraction of exhaled nitric
oxide (FeNO) shows promise as a novel biomarker of peanut allergy.
Reproducibility of these measures has not been determined. The aim was to assess
the accuracy and reproducibility (over a time-period of at least 12 months) of
SPT to Ara h2 in comparison with four predictors of clinical peanut allergy
(Peanut SPT, Ara h2 specific Immunoglobulin E (sIgE), Peanut sIgE and FeNO).
METHODS: Twenty-seven children were recruited in a follow-up of a prospective
cohort of fifty-six children at least 12 months after an open-labelled peanut
food challenge. Their repeat assessment involved a questionnaire, SPT to peanut
and Ara h2 purified protein, FeNO and sIgE to peanut and Ara h2 measurements.
RESULTS: Ara h2 SPT was no worse in accuracy when compared with peanut SPT, FeNO,
Ara h2 sIgE and peanut sIgE (AUC 0.908 compared with 0.887, 0.889, 0.935 and
0.804 respectively) for predicting allergic reaction at previous food challenge.
SPT for peanut and Ara h2 demonstrated limited reproducibility (ICC = 0.51 and
0.44); while FeNO demonstrated good reproducibility (ICC = 0.73) and sIgE for
peanut and Ara h2 were highly reproducible (ICC = 0.81 and 0.85). CONCLUSIONS: In
this population, Ara h2 SPT was no worse in accuracy when compared with current
testing for the evaluation of clinical peanut allergy, but had-like peanut SPT
poor reproducibility. FeNO, peanut sIgE and Ara h2 sIgE were consistently
reproducible despite an interval of at least 12 months between the repeated
measurements.
PMID- 27499765
TI - Prevalence and clinical features of adverse food reactions in Portuguese adults.
AB - BACKGROUND: Only one previous study, via telephone call, on the prevalence of
self-reported food allergies has been performed in Portugal, in a small sample of
adults. The objective of this study was to determine the prevalence of self
reported and probable food allergy, analyze the clinical features and involved
foods in Portuguese adults. METHODS: Population-based, cross-sectional study
performed in various healthcare centres from central Portugal. All 1436 randomly
selected individuals (median age: 45 years, 50.6 % female) replied to a validated
food allergy questionnaire by phone. Those who reported an adverse food reaction
were invited to come to the hospital, where clinical history was taken, skin
prick (SPT) and prick-prick skin (SPPT) tests were performed and food allergen
specific IgE levels (sIgE) were determined. An open oral challenge was performed
in selected cases. Cases of positive clinical history of immediate (up to 2 h
after ingestion) reaction in association with positive food sIgE levels and/or
skin prick tests were classified as IgE-associated probable food allergy. Cases
of positive clinical history of delayed (more than 2 h after ingestion) and
negative food sIgE levels independently of positive SPT or SPPT results were
classified as non-IgE associated probable food allergy. RESULTS: The prevalence
of probable food allergy in our sample was 1 %, with shellfish and fish as the
most frequently implicated foods. IgE-mediated probable food allergy occurred in
0.71 % of cases, with shellfish, peanut and nuts mainly involved. Cutaneous
symptoms were most frequently reported. Prevalence values and food types were
discrepant between self-reported and probable food allergies. CONCLUSIONS: The
prevalence of probable food allergies in Portuguese adults is low, is mostly
related to shellfish, peanut and nuts and most frequently involves cutaneous
symptoms.
PMID- 27499766
TI - Specific immunotherapy ameliorates ulcerative colitis.
AB - BACKGROUND: Hypersensitivity reaction to certain allergens plays a role in the
pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the
effect of specific immunotherapy in a group of IBD patients. METHODS: Patients
with both ulcerative colitis (UC) and food allergy were recruited into this
study. Food allergy was diagnosed by skin prick test and serum specific IgE. The
patients were treated with specific immunotherapy (SIT) and Clostridium butyricum
(CB) capsules. RESULTS: After treating with SIT and CB, the clinical symptoms of
UC were markedly suppressed as shown by reduced truncated Mayo scores and
medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor
necrosis factor (TNF)-alpha were also suppressed. Treating with SIT alone or CB
alone did not show appreciable improvement of the clinical symptoms of UC.
CONCLUSIONS: UC with food allergy can be ameliorated by administration with SIT
and butyrate-production probiotics.
PMID- 27499767
TI - A role for auto-immunity in chronic rhinosinusitis? Lessons learned from sub
epidermal bullous disorders of the skin.
AB - Chronic rhinosinusitis (CRS) is a frequent chronic condition, which has origins
in complex interactions between genetic, immunological and microbial factors. The
role of auto-immunity in CRS remains unclear, although recent studies have
started to emerge in CRS patient refractory to maximal medical management. We
discuss the possible auto-immunity link between CRS and other skin diseases, in
particular acquired bullous dermatoses, and review the current evidence. We raise
additional considerations for auto-immunity from both research and clinical
standpoints.
PMID- 27499768
TI - The Diagnosis of HIV Infection in Infants and Children.
AB - It is estimated that the number of HIV infected children globally has increased
from 1.6 million in 2001 to 3.3 million in 2012. The number of children below 15
years of age living with HIV has increased worldwide. Published data from recent
studies confirmed dramatic survival benefit for infants started anti-retroviral
therapy (ART) as early as possible after diagnosis of HI. Early confirmation of
HIV diagnosis is required in order to identify infants who need immediate ART.
WHO has designed recommendations to improve programs for both early diagnoses of
HIV infection and considering ART whenever indicated? It is strongly recommended
that HIV virologocal assays for diagnosis of HIV have sensitivity of at least 95%
and ideally greater than 98% and specificity of 98% or more under standardized
and validated conditions. Timing of virological testing is also important.
Infants infected at or around delivery may take short time to have detectable
virus. Therefore, sensitivity of virological tests is lower at birth. In utero
HIV infection, HIV DNA or RNA can be detected within 48 h of birth and in infants
with peripartum acquisition it needs one to two weeks. Finally it is emphasized
that all laboratories performing HIV tests should follow available services
provided by WHO or CDC for quality assurance programs. Both clinicians and staffs
providing laboratory services need regular communications, well-defined SOPs and
nationally validated algorithms for optimal use of laboratory tests. Every
country should use assays that have been validated by national reference
laboratory.
PMID- 27499769
TI - Validity of Selected WBC Differentiation Flags in Sysmex XT-1800i.
AB - BACKGROUND: Automatic Cell Counter devises make the CBC differential very easy
and delivering the results in few second. However, the problem with this device
is facing a flag requires a time-consuming microscopic review of the specimen
which causes unacceptable wait times for patient as well as costs for
laboratories. In this study, we calculated the validity of WBC diff flags in
Sysmex XT-1800i. In addition, we verified the correlation between manual and
automated samples. METHODS: Overall, 1095 flagged samples were selected in the
period of 6 weeks (Imam Hospital complex, Tehran Iran, 2014). The results of both
automated and manual counting of the samples were carefully studied and compared.
Totally, 624 NRBC flags, 450 Blast flags, 155 abnormal WBC Scatter gram flags,
140 Eosinophilia flags and 468 Monocytosis flags were identified. RESULTS:
Considering NRBC and blast flags there was a significant difference between our
manual counted and automated counted NRBCs and blasts (P<0.05). There was no
significant difference between automated and manual counting of flags for WBC
Scatter gram. A significant difference between automated and manual counting data
in flags, eosinophilia and monocytosis was foun (P<0.05). CONCLUSION: We propose
the NRBC flags to be ignored and report negative except for the neonatal ward,
and the Blasts flags to be ignored and report negative in all the cases. The WBC
Scatter gram should be report positive. For eosinophilia and monocytosis flags,
we propose, the Sysmex results should be considered correct and the manual
checking would not be necessary.
PMID- 27499770
TI - Maspin Gene Expression in Invasive Ductal Carcinoma of Breast.
AB - BACKGROUND: The breast cancer is the most prevalent cancer among women, on the
other hand absence of myoepithelial cells play a pivotal role in pathogenesis of
this cancer. Thus we aimed to investigate the possible abilities of the molecular
assay technique to find a relationship between mammary serine protease inhibitor
(Maspin) gene expression possibly secreted by myoepithelial cells, grade of
breast cancer and other prognostics factors (ER, PR, and c-erb-B2). METHODS:
Paraffin embedded blocks of 31 breast cancer patients together with two normal
breast tissues were used for IHC staining and Maspin gene RNA detection uses the
real-time PCR method. Applying QIAGEN kit, we were able to measure Maspin RNA and
Extract the cDNA of different samples for evaluating the Maspin RNA level.
RESULTS: We found that the RNA level was considerably lowerin these cancer
samples compared with normal samples. In addition, different grades of breast
cancer in the obtained results adopt some distinguishable values. The Maspin
expression in samples with grades II and III is much lower than the ones in
normal group (P<0.05) which could be considered as a promising way in diagnosing
of this disease. The results showed no considerable differences in Maspin gene
expression of the c-erb-B2 scores in the tumor group except the samples having
score 0. The other observation of this research study confirmed that Maspin gene
expression couldn't show any differences between the values of both ER and PR in
different scores of the tumor group. On the other hand, the cDNA of these
patients showed lower values compared with normal samples. CONCLUSION: Maspin
expression was reduced in samples with grade II& III of invasive ductal
carcinoma. Based on expression of Maspin Inc-erb-B2, it seems that more
expression happened in normal group comparing with different scores of it. We
could suggest that there was a reverse relationship between tumor formation and
Maspin gene expression. These results showed possible role of Maspin as
prognostic factor.
PMID- 27499771
TI - Designing and Construction of a DNA Vaccine Encoding Tb10.4 Gene of Mycobacterium
tuberculosis.
AB - BACKGROUND: Tuberculosis (TB) remains as a major cause of death. Construction of
a new vaccine against tuberculosis is an effective way to control it. Several
vaccines against this disease have been developed. The aim of the present study
was to cloning of tb10.4 gene in pcDNA3.1(+) plasmid and evaluation of its
expression in eukaryotic cells. METHODS: Firstly, tb10.4 fragment was amplified
by PCR and the PCR product was digested with restriction enzymes. Next, it was
cloned into pcDNA3.1(+) plasmid. Following that, pcDNA3.1(+)/tb10.4 recombinant
plasmid was transfected into eukaryotic cells. RESULTS: 5700 bp band for
pcDNA3.1(+)/tb10.4 recombinant plasmid and 297 bp fragment for tb10.4 were
observed. Cloning and transfection were successful. CONCLUSION: Successful
cloning provides a basis for the development of new DNA vaccines against
tuberculosis.
PMID- 27499772
TI - Correlation between Gleason Scores in Needle Biopsy and Corresponding Radical
Prostatectomy Specimens: A Twelve-Year Review.
AB - BACKGROUND: Presence of discordance between the Gleason score on needle biopsy
and the score of radical prostatectomy specimen is common and universal. In this
study, we determined the accuracy of Gleason grading of biopsies in predicting
histological grading of radical prostatectomy specimens and the degree of
overgrading and undergrading of prostatic adenocarcinoma in our center, which is
one of the referral centers in Tehran. METHODS: In this retrospective study, we
analyzed the results of prostate needle biopsies and subsequent prostatectomies
diagnosed at the Pathobiology Laboratory Center, Tehran, Iran in 45 patients
between 2002 and 2013. Preoperative clinical data and the information from biopsy
and prostatectomy specimens were collected. The accuracy, sensitivity,
specificity, and positive and negative predictive values of different grades and
groups were assessed. Pearson and Spearman correlation coefficient were used to
determine the relation of different variables. RESULTS: The biopsy Gleason score
was identical to the scores in prostatectomy specimens in 68.2% cases, while
31.8% were discrepant by 1 or 2 Gleason score. We had 9.1% downgrading and 22.7%
cases upgraded after prostatectomy. The sensitivity and positive predictive value
was 86% and 79% for low grade, 67% and 75% for moderate grade, and 80% and 80%
for high-grade tumors, respectively. CONCLUSION: Overall, the reliability of
Gleason grading of needle biopsies in predicting final pathology was satisfavory.
Moderate grade group was the most difficult to diagnose in needle biopsy.
PMID- 27499773
TI - Immunogenicity of Four Doses of Double-Strength Intramuscular Hepatitis B.
AB - BACKGROUND: Hepatitis B virus potentially accelerates graft rejection and
mortality in renal transplantation population. Vaccination of graft candidates
without prior immunization against HBV seems essential before transplantation but
some candidates of transplantation have not received HBV vaccine at the time of
receiving graft. We aimed to evaluate immunogenicity of an enhanced regimen (4
doses of double-strength intramuscular shots) after kidney transplantation in
candidates without history of prior HBV vaccination. METHODS: This quasi
experimental study was conducted, 49 renal graft recipients in Sina Hospital
(Tehran University of Medical Sciences, Tehran, Iran) of age >18, receiving graft
within past 6 months and negative history of hepatitis B vaccination from 2010
2011. Participants received 40 MUg intramuscular (IM) shots of a recombinant
vaccine in the months 0, 1, 2 and 6. The titer of HBsAb was measured 8 weeks
after the 3(rd) and 4(th) injections. Cases with HBsAb titers less than 10 mIu/ml
were considered as non-responder while antiHBs>=10 mIu/ml was considered
protective. RESULTS: The overall response rate was 57.14% (28/49 patients).
Protective HBsAb titers were detected in 44.89% patients following 3(rd) dose and
reached to 57.14% after injecting the 4(th) shots. The mean HBsAb titers were
50.00 (+/-88.35) mIu/ml and 229.45 (+/-356.56) mIu/ml after the 3(rd) and 4(th)
shots respectively. Responders showed significantly younger age in comparison to
non-responders (P=0.013). The vaccine was well tolerated in all patients with no
side effects. CONCLUSIONS: Regarding the relative good response rate following
HBV vaccination in graft recipients, we suggest a post-transplantation enhanced
regimen of 4-dose double-strength IM shots against HBV in patients without prior
immunization.
PMID- 27499774
TI - Can Trimodal Distribution of HbS Levels in Sickle Cell Traits Be Used To Predict
the Associated Alpha-Thalassemia For Screening Cases in Central India?
AB - BACKGROUND: Until now, trimodal distribution of HbS has been seen by six
different studies in the world when associated with alpha-thalassemia with
confirmation by corresponding alpha-genotyping studies. The RBC indices reduce as
alpha-globin genes reduce in sickle cell trait (SCT) patients, which decreases
the extent of intra-vascular sickling and thus betters the clinical course of the
patients. This is a pioneer study conducted on Central Indian poor population to
use the already proven six studies to screen associated alpha-thalassemia in SCT
patients thus, circumventing the much costlier alpha-genotyping studies.
Moreover, it aimed to study the haematological parameters in such cases. METHODS:
The study was performed at RHDMC, IGGMC, Nagpur, India from 2003 to 2012. The
sample population was suspected cases of haemolytic anaemia. CBC and RBC indices
were obtained by a cell analyzer. The sickle solubility test positively screened
cases were confirmed by agar-gel haemoglobin electrophoresis at pH 8.6. Finally,
quantitative assessment of haemoglobin variants was performed by HPLC. RESULTS:
Out of total 5819 cases over ten years, 933 cases were sickle heterozygotes.
Overall, 180/933 subjects were predicted to be homozygous alpha-thalassemia and
338/933 were heterozygous alpha-thalassemia, based on trimodal distribution of
HbS. CONCLUSION: Genotyping is costlier for majority of the poor non-affording
patients in Indian government set-ups, so this study is suitable to screen for
associated alpha-thalassemia in SCT patients.
PMID- 27499775
TI - Molecular Detection of Ureaplasma urealyticum from Prostate Tissues using PCR
RFLP, Tehran, Iran.
AB - BACKGROUND: In most cases, prostatitis can be caused by a bacterial agent such as
Ureaplasma urealyticum. Considering to the cumbersome of the culture method for
the detection of Ureaplasma species in clinical samples such as prostate; PCR
method that is faster and more appropriate than the cultivation methods, can be
utilized for the detection of U. urealyticum and U. parvum. PCR-RFLP method can
differentiate both biovars and assist in studies of the clinical diagnosis,
epidemiology and pathology of this species in human. The aim of this study was to
molecular detection of U. urealyticumin in prostate tissue samples based on PCR-
RFLP. METHODS: Two hundred prostate tissue samples were collected from patient
suffering from prostatitis. The PCR assay was used to amplify a 559 bp fragment
of 16S-23SRNA interspace region of Ureaplasma. After sequencing, PCR products
from positive samples were digested with TaqI restriction enzyme. RESULTS: Seven
cases (3.5%) out of 200 prostate tissue samples were positive for U. urealyticum.
Results of PCR products sequencing demonstrated that all isolates were U. parvum
biovar. PCR-RFLP results shown that there was not any differentiation in pattern
of enzymatic digestion, in addition, all isolates were U. parvum, serovar 3.
DISCUSSION: U. urealyticum can be one of the causing agents of prostatitis. Using
PCR-RFLP with specific primer and restriction enzyme is a rapid and cost-effect
method for detection and differentiation of Ureaplasma from clinical samples.
PMID- 27499776
TI - Comparing Rapid and Specific Detection of Brucella in Clinical Samples by PCR
ELISA and Multiplex-PCR Method.
AB - BACKGROUND: Rapid diagnosis and differentiation of Brucella is of high importance
due to the side effects of antibiotics for the treatment of brucellosis. This
study aimed to identify and compare PCR-ELISA as a more accurate diagnositc test
with other common molecular and serological tests. METHODS: In this experimental
and sectional study, during March 2014 to Sep 2015, 52 blood samples of suspected
patients with clinical symptoms of brucellosis were evaluated in medical centers
all over Iran with serum titers higher than 1:80. Using two pairs of specific
primers of Brucella abortus, B. melitensis and DIG-dUTP, Fragment IS711 (The
common gene fragment in B. melitensis and B. abortus) was amplified. DIG-ELISA
was performed using specific probes of these 2 species of Brucella and patterns
were subsequently analyzed, then positive responses were compared by detecting
gel electrophoresis. RESULTS: PCR-ELISA method detected all 28 samples from 52
positive samples. Its sensitivity was 6.0 pg concentration of genomic DNA of
Brucella. In gel electrophoresis method, 22 samples of all positive samples were
detected. PCR-ELISA was more efficient than PCR and bacterial culture method at P
value <0.05. CONCLUSION: PCR-ELISA molecular method is more sensitive than other
molecular methods, lack of mutagenic color and also a semi-quantitative ability.
This method is more effective and more accurate compared to PCR, serology and
culture of bacteria. PCR-ELISA does not have false responses. The limitation of
this method is detection of bacteria in the genus compared to Multiplex PCR and
Gel Electrophoresis.
PMID- 27499777
TI - Preanalytical Errors in Hematology Laboratory- an Avoidable Incompetence.
AB - BACKGROUND: Quality assurance in the hematology laboratory is a must to ensure
laboratory users of reliable test results with high degree of precision and
accuracy. Even after so many advances in hematology laboratory practice, pre
analytical errors remain a challenge for practicing pathologists. This study was
undertaken with an objective to evaluate the types and frequency of preanalytical
errors in hematology laboratory of our center. METHODS: All the samples received
in the Hematology Laboratory of Dayanand Medical College and Hospital, Ludhiana,
India over a period of one year (July 2013-July 2014) were included in the study
and preanalytical variables like clotted samples, quantity not sufficient, wrong
sample, without label, wrong label were studied. RESULTS: Of 471,006 samples
received in the laboratory, preanalytical errors, as per the above mentioned
categories was found in 1802 samples. The most common error was clotted samples
(1332 samples, 0.28% of the total samples) followed by quantity not sufficient
(328 sample, 0.06%), wrong sample (96 samples, 0.02%), without label (24 samples,
0.005%) and wrong label (22 samples, 0.005%). CONCLUSION: Preanalytical errors
are frequent in laboratories and can be corrected by regular analysis of the
variables involved. Rectification can be done by regular education of the staff.
PMID- 27499778
TI - Rad51 Expression in Nasopharyngeal Carcinoma and Its Association with Tumor
Reduction: A Preliminary Study in Indonesia.
AB - BACKGROUND: Overexpression of Rad51 protein in many tumor cells has been proven
to increase radioresistance and can be related to the resistance of
chemosensitivity of tumor cells. This preliminary study was conducted to
determine the relationship between the Rad51 expression level in nasopharyngeal
carcinoma and the response of the treatment based on the measurement of the tumor
reduction. METHODS: Thirteen cases of the NPCs were analyzed. The expression
levels of the Rad51 were examined from the pretreatment biopsies. Furthermore,
tumor reductions were determined based on the change in sum longest diameter of
the nasopharyngeal CT-scan before and after therapy. RESULTS: The expression
level of the Rad51 was associated with the reduction of tumor mass. The P value
was 0.049 and the correlation coefficient was 0.479. CONCLUSION: The tumor cells
Rad51 expression levels may affect the tumor reduction of NPC after the therapy.
PMID- 27499779
TI - Pituitary Chondrosarcoma presenting as a sellar and suprasellar mass with
parasellar extension: An Unusual presentation.
AB - Chondrosarcoma is a mesenchymal tumor composed of tumor cells producing
cartilage. It is more common in older age and often affects the axial skeleton.
We report a rare case of chondrosarcoma mimicking a sellar and suprasellar mass
with parasellar extension. A 40 yr woman presented with decreasing visual acuity
and headache. Magnetic resonance (MR) image revealed a cystic sellar and
suprasellar mass with parasellar extension showing mild enhancing solid
component. It favored the diagnosis of craniopharyngioma. The patient underwent
trans-sphenoidal partial resection of the tumor resulting in removal of the
sellar mass. However, the suprasellar mass could not be excised completely due to
limited surgical field. The pathologic diagnosis was chondrosarcoma. Eight months
after the operation, pterional approach was performed to remove the remaining
mass. Intraoperative findings confirmed that the mass originated from dorsum
sellae.
PMID- 27499780
TI - Apocrine Metaplasia in Intraductal Papilloma with Foci of DCIS: A Friend or Foe?
AB - Malignant papillary neoplasms of the breast comprise a number of microscopically
distinct lesions, where apocrine metaplasia is commonly found in papillomas
compared to other papillary lesions including papillary carcinomas. However,
association of apocrine metaplasia in papilloma with Ductal Carcinoma in Situ
(DCIS) is not very well defined. The lesions with apocrine metaplasia are not
only difficult to categories, but also there is controversy regarding their
relative risk of subsequent carcinoma development. A case of extensive apocrine
differentiation in duct papilloma with DCIS developing in the background of
papillomatosis, posing a diagnostic dilemma for the pathologist and a therapeutic
challenge for the surgeon, is hereby reported for its uniqueness and rarity.
Awareness of this association should be kept in mind by both the pathologist as
well as clinician for optimal therapeutic intervention.
PMID- 27499781
TI - Granulomatous Response with Breast Cancer: A Case Report.
AB - Granulomatous response in association with breast cancer and within the cancer
draining lymph nodes is an extremely rare phenomenon. Granulomatous inflammation
is an immune response commonly seen against infectious agents and certain non
neoplastic conditions. The etiopathogenesis of granulomas associated with
malignancies is not clear but it may be because of an immunologic reaction to
tumour antigens. We hereby report a 50-yr-old postmenopausal female presented to
Surgical Outpatient Department, Aligarh Muslim University, India, with complaints
of lump and pain in her left breast for 6 months. We have also discussed about
its etiopathogenesis, final diagnosis, treatment & patient outcome.
PMID- 27499782
TI - Recurrent Ancient Intraosseous Neurilemmoma of Maxilla: A Rare Case Report.
AB - Neurilemmomas are benign tumors of peripheral nerve sheath Schwann cells. One of
the variants of neurilemmoma is the ancient type of neurilemmoma characterized by
degenerative features such as cystic degeneration, calcification, hemorrhage and
hyalinization which could be easily misdiagnosed. Their occurrence in oral cavity
is extremely rare and intraosseous type occurring in maxilla is exceedingly rare
with very few cases being published in literature. A 38 year old male patient
reported with a chief complaint of swelling over the left cheek and left upper
back region since 10 months. The case is of recurrent intraosseous ancient
neurilemmoma in the maxilla in the patient which is distinctive for the lesion.
This unique case presented with distinct histologic architectural pattern of
ancient neurilemmoma showing degenerative changes such as cystic degeneration and
recurred within a short duration of time.
PMID- 27499783
TI - Acinic Cell Carcinoma of the Parotid Gland with Four Morphological Features.
AB - Acinic cell carcinoma arising in salivary glands is a rare tumor, accounting for
2% to 5% of the primary neoplasms of the parotid gland. When these tumors are
well-differentiated, the neoplasia has innocuous aspect, due to the similarity to
normal parotid tissue. This makes the diagnosis difficult. Initially the
malignancy of this tumor was uncertain; however, recent studies have declared it
as malignant. The female / male ratio is 3:2. The nodule usually presents as
solitary and well defined shape. Several authors have used different terms to
describe histomorphological patterns of these tumors. Four descriptive categories
(solid, microcystic, papillary-cystic and follicular) are useful for
pathologists. Here we report a case of a 49 yr old man with a left parotid nodule
of 5 cm. Parotidectomy was performed at the Hospital Universitario Miguel Servet,
in Zaragoza (Spain). The microscopy showed a tumor with acinic semblance, having
the four morphologic patterns previously described. The morphological and
immunohistochemical study was consistent with the diagnosis of acinic cell
carcinoma.
PMID- 27499784
TI - Localized Leishmania Lymphadenitis Etiologic Agent Identified as Leishmania
tropica Using Gene Sequencing.
PMID- 27499785
TI - Anemia during Hospitalization in the Patients with Ebola Virus Disease.
PMID- 27499786
TI - Ebola Infection and Diabetes Mellitus.
PMID- 27499787
TI - Inhibition of P-glycoprotein expression and function by anti-diabetic drugs
gliclazide, metformin, and pioglitazone in vitro and in situ.
AB - P-glycoprotein (P-gp) is a trans-membrane drug efflux pump. Several drugs are P
gp substrates. Some drugs may affect the activity of P-gp by inhibiting its
function, resulting in significant drug-drug interactions (DDIs). It is critical
to understand which drugs are inhibitors of P-gp so that adverse DDIs can be
minimized or avoided. This study investigated the effects of gliclazide,
metformin, and pioglitazone on the function and expression of P-gp. Rhodamine 123
(Rh 123) efflux assays in Caco-2 cells and western blot testing were used to
study in vitro the effect of the drugs on P-gp function and expression. The in
situ rat single-pass intestinal permeability model was developed to study the
effect of the drugs on P-gp function. Digoxin and verapamil were used as a known
substrate and inhibitor of P-gp, respectively. Digoxin levels in intestinal
perfusion samples were analyzed by high-performance liquid chromatography.
Intestinal effective permeability (Peff) of digoxin in the presence of 0.1, 10,
and 500 MUM gliclazide, 100 and 7000 MUM metformin, and 50 and 300 MUM
pioglitazone was significantly increased relative to the digoxin treated cells (P
< 0.01). P-gp expression was decreased by gliclazide, metformin and pioglitazone.
Intracellular accumulation of Rh 123 by the drugs increased, but the differences
were not significant relative to the control cells (P > 0.05). It was found that
gliclazide, metformin, and pioglitazone inhibited P-gp efflux activity in situ
and down-regulated P-gp expression in vitro. Further investigations are necessary
to confirm the obtained results and to define the mechanism underlying P-gp
inhibition by the drugs.
PMID- 27499788
TI - Theoretical design of a new chimeric protein for the treatment of breast cancer.
AB - p28 and NRC peptides are two anticancer peptides with various mechanisms have
shown to be effective against breast cancer. Therefore, it seems that
construction of a chimeric protein containing the two peptides might cause
synergistic cytotoxic effects. However, since the two peptides bear opposite
charges, production of a chimeric protein in which the two moieties do not
intervene each other is difficult. In this study, our goal was to find a suitable
peptide linker for the new chimeric protein in a manner that none of the peptides
intervene the other's function. We selected some linkers with different
characteristics and lengths and created a small library of the chimeric proteins
harboring these linkers. Homology modeling and molecular dynamic simulation
revealed that (PA)5P and (EAAAK)3 linkers can separate the p28 and NRC peptides
effectively. Thus, the chimeric protein linked with (PA)5P or (EAAAK)3 linkers
might show synergistic and stronger anticancer effects than the separate peptide
moieties because they could exert their cytotoxic effects freely which is not
influenced by the other part.
PMID- 27499789
TI - Antidiarrhoeal assessment of hydroalcoholic and hexane extracts of Dracocephalum
kotschyi Boiss. and apigenin in mice.
AB - Dracocephalum kotschyi Boiss, a member of Labiatae family, is a native plant to
Iran, which has been reported to have immunomodulatory, antihyperlipidemic and
antispasmodic activities. The objective of this research was to study the
antispasmodic and antidiarrhoeal activities of hydroalcoholic and hexane extracts
of D. kotschyi in mice. Furthermore, the antidiarrhoeal and antispasmodic effect
of apigenin, a flavonoid constituent of D. kotschyi, was also studied.
Hydroalcoholic and hexane extracts were obtained from aerial part of D. kotschyi
using percolation method. Antispasmodic effect of the test compounds was assessed
by measurement of small intestine transit following oral administration of a
charcoal meal. Diarrhoea was induced by administration of either castor oil (0.5
ml) or magnesium sulphate (MgSO4) (10% w/v solution). Both the hydroalcoholic and
hexane extracts of D. kotschyi (10 and 20 mg/kg) reduced the intestinal charcoal
meal transit. Loperamide (2 mg/kg) and apigenin (2 and 10 mg/kg) inhibited
intestinal movement of the charcoal meal and also inhibited castor oil and MgSO4
induced diarrhoea. The hydroalcoholic and hexane extracts of D. kotschyi (10 and
20 mg/kg) also significantly inhibited the castor oil and MgSO4-induced diarrhoea
in mice in comparison with the vehicle-treated control groups. This study
confirms that both the hydroalcoholic and hexane extracts of D. kotschyi has
antispasmodic and antidiarrhoeal properties in vivo and could be a suitable
remedy for treatment of gastrointestinal disorders in which smooth muscle spasm
and/or diarrhoea plays a significant roles.
PMID- 27499790
TI - Synthesis and cytotoxicity evaluation of some new 6-nitro derivatives of thiazole
containing 4-(3H)-quinazolinone.
AB - Quinazolinones are a group of fused heterocyclic compounds which have valuable
biological properties including cytotoxic, antibacterial and antifungal
activities. Thiazole group-containing compounds have been also reported to have a
wide range of biological activities such as antitumor, anti-inflammatory,
analgesic and antibacterial effects. Due to valuable cytotoxic effects of both
thiazole groups and quinazoline derivatives, in this study a series of
quinazolinone-thiazole hybrids were synthesized and evaluated for their cytotoxic
effects on three cell lines including MCF-7, HT-29, and PC-3. Among tested
compounds (quinazolinones and three intermediates), k5 and k6 showed highest
cytotoxic activities against PC3 cell line. K6 and C were most active compounds
against MCF7 and K6 showed best cytotoxicity on HT-29 cell line.
PMID- 27499791
TI - Wound-healing and antimicrobial properties of dichloromethane fraction of Dialium
guineense (Wild) fruit coat.
AB - This research established the scientific bases for the folkloric use of the
neglected Dialium guineense fruit coat in wound and microbial infection
management in Nigeria. The phytochemical analysis of the crude extract, fractions
and sub-fractions was performed by standard methods. Agar well diffusion protocol
was adopted for the antimicrobial assay while the wound healing properties was
determined by full thickness skin excision wound model. Phytochemical analysis
showed high relative proportion of alkaloids (6.05 +/- 0.98 %), saponins (3.91 +/
0.02 %) and tannins (1.86 +/- 0.05 %). The only active fraction (DF) and sub
fraction (DF-5) were effective against Gram-positive (inhibition zone diameters,
IZDs, 8-10 mm and 11-15 mm) and Gram-negative (IZDs, 15-19 mm and 16-21 mm)
bacteria and fungi (6-8 mm) compared with 20-24 mm and 18-19 mm of the standard
(ciprofloxacin) respectively. Fifty mg/kg of the DF-5 showed nearly equal
percentage wound healing post-surgery days to Cicatrin(r). The 50 mg/kg dose of
DF and DF-5 showed more than 50 % wound healing at 10(th) day post-surgery, 50
mg/kg crude extract showed 54 % on day 14 while distilled water showed 56 % wound
healing on day 17 with no sign of infection in all animal groups. All the
treatments were significantly (P<0.01) different from control (distilled water)
in wound healing by the 10(th) and 17(th) post-surgery days. The studies revealed
that the fruit coat, which hitherto was treated as wastes could be explored for
antimicrobial and wound healing properties against the backdrop of continually
emerging antibiotic resistant strains of microorganisms.
PMID- 27499792
TI - Effect of hydroalcoholic extract of Anethum graveolens leaves on the dentate
gyrus of the hippocampus in the epileptic mice: a histopathological and
immunohistochemical study.
AB - Anethum graveolens or Dill (local name: Shevid) belongs to the family of Apiaceae
(Umbelliferae) and is used traditionally for the treatment of convulsion and
diabetes in Iran. This study aimed to investigate the effect of hydroalcoholic
extract of A. graveolens leaves on the histology of the dentate gyrus of the
hippocampus in the epileptic mice kindled by Pentylenetetrazole (PTZ). In this
experimental study, the epileptic BALB/c mice kindled by PTZ were randomly
divided into four groups of 10 animals each. Three experimental groups received
250, 500 and 750 mg/kg/day of A. graveolens extract for 21 days. The control
group received phosphate-buffered saline (PBS). After the treatment period, the
mice were anesthetized, and their hippocampi were dissected for the
histopathological analysis, and immunohistochemical analysis for caspase-3
activity. Histopathological examinations showed that the mean numbers of the
healthy neuronal cells in the dentate gyrus of the mice received 500 mg/kg/day of
A. graveolens extracts were significantly higher than those of the mice received
250 and 750 mg/kg/day of the extracts as well as the control group (P < 0.05 and
P < 0.001, respectively). In addition, the results of immunohistochemical
analysis revealed that in mice treated with 500 mg/kg/day of A. graveolens; the
numbers of caspase-3-positive cells in the dentate gyrus were significantly lower
than those of the two other test and the control groups. The findings of this
study suggest that 500 mg/kg/day of the A. graveolens extract could have
protective effect on the dentate gyrus of the hippocampus in the epileptic mice.
PMID- 27499793
TI - Incidence rate and pattern of clinically relevant potential drug-drug
interactions in a large outpatient population of a developing country.
AB - The objective of this study was to determine incidence rate, type, and pattern of
clinically relevant potential drug-drug interactions (pDDIs) in a large
outpatient population of a developing country. A retrospective, descriptive cross
sectional study was conducted on outpatients' prescriptions in Khorasan Razavi
province, Iran, over 12 months. A list of 25 clinically relevant DDIs, which are
likely to occur in the outpatient setting, was used as the reference. Most
frequent clinically relevant pDDIs, most common drugs contributing to the pDDIs,
and the pattern of pDDIs for each medical specialty were determined. Descriptive
statistics were used to report the results. In total, out of 8,169,142
prescriptions, 6,096 clinically relevant pDDIs were identified. The most common
identified pDDIs were theophyllines-quinolones, warfarin-nonsteroidal anti
inflammatory drugs, benzodiazepines-azole antifungal agents, and anticoagulants
thyroid hormones. The most common drugs contributing to the identified pDDIs were
ciprofloxacin, theophylline, warfarin, aminophylline, alprazolam, levothyroxine,
and selegiline. While the incidence rate of clinically relevant pDDIs in
prescriptions of general practitioners, internists, and cardiologists was the
highest, the average pDDI incidence per 10,000 prescriptions of pulmonologists,
infectious disease specialists, and cardiologists was highest. Although a small
proportion of the analyzed prescriptions contained drug pairs with potential for
clinically relevant DDIs, a significant number of outpatients have been exposed
to the adverse effects associated with these interactions. It is recommended that
in addition to training physicians and pharmacists, other effective interventions
such as computerized alerting systems and electronic prescribing systems be
designed and implemented.
PMID- 27499794
TI - Phytochemical and biological evaluation of some Sargassum species from Persian
Gulf.
AB - Sea algae are widely consumed in the world. There are several seaweeds including
brown algae which are authorized for human consumption. These plants contain
important phytochemical constituents and have various potential biological
activities. The present study investigated the presence of phytochemical
constituents and total phenolic quantity of the seaweeds Sargassum angustifolium,
Sargassum oligocystum and Sargassum boveanum. Cytotoxicity of seaweeds was tested
against HT-29, HeLa and MCF-7 cell lines. Antioxidant potential of these 3
Sargassum species was also analyzed. Cytotoxicity was characterized by IC50 of
human cancer cell lines using sulforhodamine assay. Antioxidant activities were
evaluated using 2,2-diphenyl-1- picrylhydrazil. The analysis revealed that
tannins, saponins, sterols and triterpenes were the most abundant compounds in
these Sargassum species while cyanogenic and cardiac glycosides were the least
ones. Sargassum angustifolium had the highest content of total phenolics (0.061
mg/g) and showed the highest antioxidant activity (IC50 = 0.231). Cytotoxic
results showed that all species could inhibit cell growth effectively, especially
MCF-7 cell line (IC50 = 67.3, 56.9, 60.4 for S. oligocystum, S. angustifolium and
S. boveanum respectively). Considerable phytochemicals and moderate cytotoxic
activity of S. angustifolium, S. oligocystum and S. boveanum make them
appropriate candidate for further studies and identification of their bioactive
principles.
PMID- 27499795
TI - Identification of novel bacterial DNA gyrase inhibitors: An in silico study.
AB - Owing to essential role in bacterial survival, DNA gyrase has been exploited as a
validated drug target. However, rapidly emerging resistance to gyrase-targeted
drugs such as widely utilized fluoroquinolones reveals the necessity to develop
novel compounds with new mechanism of actions against this enzyme. Here, an
attempt has been made to identify new drug-like molecules for Shigella flexneri
DNA gyrase inhibition through in silico approaches. The structural similarity
search was carried out using the natural product simocyclinone D8, a unique
gyrase inhibitor, to virtually screen ZINC database. A total of 11830 retrieved
hits were further screened for selection of high-affinity compounds by
implementing molecular docking followed by investigation of druggability
according to Lipinski's rule, biological activity and physiochemical properties.
Among the hits initially identified, three molecules were then confirmed to have
reasonable gyrase-binding affinity and to follow Lipinski's rule. Based on these
in silico findings, three compounds with different chemical structures from
previously identified gyrase inhibitors were proposed as potential candidates for
the treatment of fluoroquinolone-resistant strains and deserve further
investigations.
PMID- 27499796
TI - Frequency distribution of polymorphisms of CYP2C19, CYP2C9, VKORC1 and SLCO1B1
genes in the Yakut population.
AB - Allele frequencies of single nucleotide polymorphisms (SNPs) are variable among
different populations; therefore the study of SNPs in ethnic groups is important
for establishing the clinical significance of the screening of these
polymorphisms. The main goal of the research is to study the polymorphisms of
CYP2C9, CYP2C19, VKORC1, and SLCO1B1 in Yakuts. Genomic DNA from 229 Yakut
subjects were analyzed by real-time polymerase chain reaction (PCR) (SLCO1B1
+521T > C, VKORC1 -1639G>A, CYP2C19 +681G>A, +636G>A, CYP2C9 +430S>T, +1075A>C).
Genotype frequencies of polymorphisms in the population of the Yakuts were more
characteristic of the Asian population. The results have been included in the
software application "Lekgen" that we developed for the interpretation of
pharmacogenetic testing. The data of our study obtained on frequency carriers of
polymorphisms of genes SLCO1B1, CYP2C19, CYP2C9, VKORC1 among the Yakuts may be
useful in developing recommendations for a personalized therapy.
PMID- 27499797
TI - XAFS Data Interchange: A single spectrum XAFS data file format.
AB - We propose a standard data format for the interchange of XAFS data. The XAFS Data
Interchange (XDI) standard is meant to encapsulate a single spectrum of XAFS
along with relevant metadata. XDI is a text-based format with a simple syntax
which clearly delineates metadata from the data table in a way that is easily
interpreted both by a computer and by a human. The metadata header is inspired by
the format of an electronic mail header, representing metadata names and values
as an associative array. The data table is represented as columns of numbers.
This format can be imported as is into most existing XAFS data analysis,
spreadsheet, or data visualization programs. Along with a specification and a
dictionary of metadata types, we provide an application-programming interface
written in C and bindings for programming dynamic languages.
PMID- 27499798
TI - Impact of Psychoeducational Content Delivered Online to a Positive Psychology
Aware Community.
AB - Happiness-increasing interventions demonstrate significant variation in outcomes,
suggesting that the people who use them might be as important as the
interventions themselves to determine efficacy. In light of this, instructive
interventions might not be necessary to increase happiness given a population
with knowledge of happiness-increasing strategies. We recruited 270 participants
with knowledge of positive psychology to receive six weeks of online
psychoeducation. We explored participants' use of the website, reported use of
happiness strategies, and changes in well-being. Those who spent more time on the
website reported smaller changes in well-being than those who spent less time on
the website. Conversely, those who reported employing more happiness strategies
reported greater increases in well-being than those who used fewer strategies.
This shows that for those already familiar with positive psychology, information,
rather than instruction, might increase well-being. This has implications for
studies evaluating the efficacy of happiness-increasing interventions more
broadly.
PMID- 27499799
TI - Habsburg Austria: Experiments in Non-Territorial Autonomy.
AB - In the early twentieth century, three provinces of the Austrian half of the
Habsburg Empire enacted national compromises in their legislation that had
elements of non-territorial autonomy provisions. Czech and German politicians in
Moravia reached an agreement in 1905. In the heavily mixed Bukovina, Romanian,
Ukrainian, German, Jewish and Polish representatives agreed on a new provincial
constitution in 1909. Last but not least, Polish and Ukrainian nationalists
compromised in spring 1914, just a few months before the outbreak of the First
World War vitiated the new provisions. Even though the provisions of these
agreements varied substantially, new electoral laws introducing national
registers were at their heart. These were designed to ensure a fairer
representation of national groups in the provincial assemblies and to keep
national agitation out of electoral campaigns. The earliest compromise in Moravia
went furthest in consociational power sharing. However, the national bodies
within the provincial assembly had no right to tax their respective national
communities, and the provisions of the provincial constitutions kept the non
nationally defined nobility as an important counterbalance. The compromises in
Bukovina and Galicia, even if they categorised all inhabitants nationally,
contented themselves with even less autonomous agency for the national bodies in
the provincial assemblies and rather emphasised the symbolic elements of national
autonomy. The non-territorial approach in all three crownlands, however, was an
instrument to reorganise multi-ethnic provinces that increasingly became the
model for national compromises in other Austrian provinces.
PMID- 27499800
TI - The flagellar motor of Caulobacter crescentus generates more torque when a cell
swims backward.
AB - Caulobacter crescentus, a monotrichous bacterium, swims by rotating a single
right-handed helical filament. CW motor rotation thrusts the cell forward 1, a
mode of motility known as the pusher mode; CCW motor rotation pulls the cell
backward, a mode of motility referred to as the puller mode 2. The situation is
opposite in E. coli, a peritrichous bacterium, where CCW rotation of multiple
left-handed filaments drives the cell forward. The flagellar motor in E. coli
generates more torque in the CCW direction than the CW direction in swimming
cells 3,4. However, monotrichous bacteria including C. crescentus swim forward
and backward at similar speeds, prompting the assumption that motor torques in
the two modes are the same 5,6. Here, we present evidence that motors in C.
crescentus develop higher torques in the puller mode than in the pusher mode, and
suggest that the anisotropy in torque-generation is similar in two species,
despite the differences in filament handedness and motor bias (probability of CW
rotation).
PMID- 27499801
TI - An improved Four-Russians method and sparsified Four-Russians algorithm for RNA
folding.
AB - BACKGROUND: The basic RNA secondary structure prediction problem or single
sequence folding problem (SSF) was solved 35 years ago by a now well-known
[Formula: see text]-time dynamic programming method. Recently three methodologies
Valiant, Four-Russians, and Sparsification-have been applied to speedup RNA
secondary structure prediction. The sparsification method exploits two properties
of the input: the number of subsequence Z with the endpoints belonging to the
optimal folding set and the maximum number base-pairs L. These sparsity
properties satisfy [Formula: see text] and [Formula: see text], and the method
reduces the algorithmic running time to O(LZ). While the Four-Russians method
utilizes tabling partial results. RESULTS: In this paper, we explore three
different algorithmic speedups. We first expand the reformulate the single
sequence folding Four-Russians [Formula: see text]-time algorithm, to utilize an
on-demand lookup table. Second, we create a framework that combines the fastest
Sparsification and new fastest on-demand Four-Russians methods. This combined
method has worst-case running time of [Formula: see text], where [Formula: see
text] and [Formula: see text]. Third we update the Four-Russians formulation to
achieve an on-demand [Formula: see text]-time parallel algorithm. This then leads
to an asymptotic speedup of [Formula: see text] where [Formula: see text] and
[Formula: see text] the number of subsequence with the endpoint j belonging to
the optimal folding set. CONCLUSIONS: The on-demand formulation not only removes
all extraneous computation and allows us to incorporate more realistic scoring
schemes, but leads us to take advantage of the sparsity properties. Through
asymptotic analysis and empirical testing on the base-pair maximization variant
and a more biologically informative scoring scheme, we show that this Sparse Four
Russians framework is able to achieve a speedup on every problem instance, that
is asymptotically never worse, and empirically better than achieved by the
minimum of the two methods alone.
PMID- 27499802
TI - The Single-Case Reporting Guideline In BEhavioural Interventions (SCRIBE) 2016
Statement.
AB - Reporting guidelines, such as the Consolidated Standards of Reporting Trials
(CONSORT) Statement, improve the reporting of research in the medical literature
(Turner et al., 2012). Many such guidelines exist and the CONSORT Extension to
Nonpharmacological Trials (Boutron et al., 2008) provides suitable guidance for
reporting between-groups intervention studies in the behavioral sciences. The
CONSORT Extension for N-of-1 Trials (CENT 2015) was developed for multiple
crossover trials with single individuals in the medical sciences (Shamseer et
al., 2015; Vohra et al., 2015), but there is no reporting guideline in the
CONSORT tradition for single case research used in the behavioral sciences. We
developed the Single Case Reporting guideline In BEhavioural interventions
(SCRIBE) 2016 to meet this need. This statement article describes the methodology
of the development of the SCRIBE 2016, along with the outcome of 2 Delphi surveys
and a consensus meeting of experts. We present the resulting 26-item SCRIBE 2016
checklist. The article complements the more detailed SCRIBE 2016 explanation and
elaboration article (Tate et al., 2016) that provides a rationale for each of the
items and examples of adequate reporting from the literature. Both these
resources will assist authors to prepare reports of single case research with
clarity, completeness, accuracy, and transparency. They will also provide journal
reviewers and editors with a practical checklist against which such reports may
be critically evaluated.
PMID- 27499803
TI - On table POCUS assessment for the IVC following abdominal packing: how I do it.
AB - BACKGROUND: Some surgeons may lack proper experience in abdominal packing.
Overpacking may directly compress the inferior vena cava (IVC). This reduces the
venous return and possibly causes hypotension. Here, a new on table Point-of-Care
Ultrasound application that has been recently used to assess the effect of
abdominal packing on the IVC diameter is described. Following abdominal packing,
a small print convex array probe with low frequency (2-5 MHz) is used to
visualize the IVC. Using the B mode, the IVC can be directly evaluated through a
hepatic window between the ribs. The ultrasound beam should be vertical to the
IVC longitudinal section at its midpoint. The abdominal towels will be in front
of the IVC. This will enable us to judge whether there was overpacking on the
IVC. RESULTS: Our method demonstrates that overpacking does not compress the IVC
in a patient whose blood pressure has improved. The IVC diameter progressively
increases on table and in the ICU with active resuscitation implying that
bleeding stopped and the resuscitation was successful. Furthermore, presence of
intra-peritoneal fluid can be excluded. CONCLUSIONS: This new application of
ultrasound evaluation of IVC patency after abdominal packing is simple,
practical, easily reproducible, and can guide a less experienced surgeon in
determining if overpacking of the abdomen is the cause of hypotension. Ultrasound
findings should be correlated with the clinical picture to be useful.
PMID- 27499804
TI - The learning curve of single-port laparoscopic appendectomy performed by emergent
operation.
AB - BACKGROUND: Single-port laparoscopic appendectomy (SPLA) has the advantage of
minimizing abdominal incision scars with patient satisfaction. However, it has
the following disadvantages: it provides a narrower surgical field than
conventional laparoscopic appendectomy, which requires a considerably longer
operative time to achieve surgical skills. This study was conducted to evaluate
the learning curve for SPLA. METHODS: This study included a total of 120 patients
with acute abdomen who visited our emergency department and were diagnosed with
acute appendicitis between March 2013 and February 2015. They underwent SPLA by a
single surgeon. Patients were divided into 4 groups of 30 patients each according
to operation dates. Operative time, time to resume oral intake, length of
hospital stay, and postoperative complications were analyzed. RESULTS: The mean
operative time was 59.9 +/- 19.9 min. It was shortened after completion of 30
operations and remained unchanged until it was further shortened after completion
of 90 operations. There was no significant difference in time to resumption of
oral intake or length of hospital stay between the 4 groups. Postoperative
complications occurred in 18 patients, but the frequency of the complications was
not significantly different between the 4 groups. CONCLUSIONS: The results of
this study suggest that surgeons can achieve surgical skills for SPLA after
completion of 30 operations and more experienced surgical skills by SPLA
successfully after completion of 90 operations.
PMID- 27499805
TI - Situated learning in translation research training: academic research as a
reflection of practice.
AB - Situated learning has become a dominant goal in the translation classroom:
translation didactics is being developed in a learner-, situation- and experience
based direction, following constructivist and participatory teaching
philosophies. However, the explicit use of situated approaches has, so far, not
been the centre of attention in translation theory teaching and research
training. As a consequence, translation theory often remains unconnected to the
skills learned and topics tackled in language-specific translation teaching and
the challenges experienced in real-life translation practice. This article
reports on the results of an exploratory action research project into the
teaching of academic research skills in translation studies at Master's level.
The goal of the project is to develop and test possibilities for employing
situated learning in translation research training. The situatedness perspective
has a double relevance for the teaching project: the students are involved in an
authentic, ongoing research project, and the object of the research project
itself deals with authentic translation processes at the workplace. Thus, the
project has the potential to improve the expertise of the students as both
researchers and reflective practitioners.
PMID- 27499806
TI - A German e-learning-training in the context of early preventive intervention and
child protection: preliminary findings of a pre-post evaluation.
AB - BACKGROUND: In recent years, a number of government-sponsored initiatives have
been implemented in Germany that are focused on early preventive intervention in
child protection. In response to the need for interdisciplinary training in this
area, the internet-based e-learning program "Early Preventive Intervention and
Child Protection" was developed for professionals in the child welfare and health
care systems working with families with infants and toddlers. The program is
currently undergoing evaluation for effectiveness and user satisfaction. METHODS:
In a pre-post design, users are requested to complete questionnaires that assess
three measures of expertise: theoretical knowledge of relevant fields, the
ability to correctly identify subtle signals of infant communication, and the
ability to assess maternal sensitivity. This article presents the contents of the
program and the pre-training results (N = 1.294 participants). Descriptive
analyses as well as Pearson correlations and Bonferroni corrections of error were
conducted using the statistical program SPSS v. 21.0. RESULTS: The findings show
that a wide range of professionals are making use of the program, and that their
existing theoretical knowledge about early preventive intervention, as well as
their ability to identify subtle signals of infant communication, is relatively
good. However, their ability to assess maternal sensitivity, which is considered
a crucial indicator for the risk of child abuse, was low. CONCLUSIONS: The
outcome of the pre-training results indicates that professionals working in the
area of child protection need to develop more capability in recognizing maternal
sensitivity, in order to ensure early detection of families who are at risk and
thus in need of support. Finally, the number of years of professional experience
did not correlate with the scores on any of the three measures, which emphasizes
the importance of providing interdisciplinary training in this area for all those
working in child and family services, regardless of background.
PMID- 27499807
TI - Mixed tenure communities as a policy instrument for educational outcomes in a
deprived urban context?
AB - This article considers mixed community strategies, enacted through planning and
regeneration policies, as a policy approach to the improvement of educational
outcomes in schools. Analysis is undertaken of educational outcomes across
secondary schools in Glasgow. The level of owner occupation in the catchment is
positively associated with both examination results at S4 and positive
destinations post-school, particularly at the more deprived end of the school
spectrum. The results suggest that tenure mix may be both directly and indirectly
related to school performance, with neighbourhood context effects not being
entirely mediated through the school context.
PMID- 27499808
TI - Mental illness stigma and engagement in an implementation trial for Cognitive
Processing Therapy at a diverse community health center: a qualitative
investigation.
AB - The present study aimed to describe associations between various types of mental
health stigma and help-seeking behaviors among ethnically diverse clients with
posttraumatic stress disorder (PTSD) served by an urban community health clinic.
The present study draws qualitative data from a parent National Institute of
Mental Health Study that aims to identify barriers and facilitators of
implementing Cognitive Processing Therapy (CPT) for PTSD. A total of 24
participants from the initial phase of the trial were included in the present
study. Mental health stigma emerged as one notable barrier to seeking mental
health treatment, as participants described how experiences of environment-level
stigma, internalized (self-)stigma and perceived (felt) stigma from their family,
friends and previous healthcare providers influenced their decisions to seek
care. Despite these barriers to help seeking, many clients also reported that
positive interactions with informal and formal support systems, and encouragement
from study therapists, helped to combat mental health stigma and facilitate
decisions to participate in an implementation trial for CPT. Findings suggest
that providers in community health settings may need to attend directly to stigma
at the initiation of mental health treatment.
PMID- 27499809
TI - Evaluation of the two-step treatment with ionic liquids and alkali for enhancing
enzymatic hydrolysis of Eucalyptus: chemical and anatomical changes.
AB - BACKGROUND: The biomass recalcitrance resulting from its chemical compositions
and physical structures impedes the conversion of biomass into fermentable
sugars. Pretreatment is a necessary procedure to increase the cellulase
accessibility for bioconversion of lignocelluloses into bioethanol.
Alternatively, ionic liquids, a series of promising solvents, provide unique
opportunities for pretreating a wide range of lignocellulosic materials. In this
study, a two-step treatment including ionic liquids pretreatment and successive
alkali fractionations was performed on Eucalyptus to achieve a high enzymatic
digestibility. The compositional and structural changes of Eucalyptus cell walls
and their possible effect on saccharification ratio were comprehensively
investigated. RESULTS: After the ionic liquids pretreatment, the cell walls
became loose and even swelled, accompanying with the decrease of cellulose
crystallinity. As compared to the simplex ionic liquids pretreatment, the
integrated process resulted in the significant removal of hemicelluloses and
lignin, enhancing the disruption of the cell walls and increasing the exposure of
cellulose, which led to a higher conversion of cellulose to glucose. The glucose
yield of Eucalyptus underwent the combination of [Bmim]OAc and alkali treatments
reached the maximum (90.53 %), which was 6.6 times higher than that of the
untreated Eucalyptus. The combination of chemical compositions and physical
structure of Eucalyptus affected the efficiency of cellulose enzymatic
hydrolysis. Especially, the changes of cellulose crystallinity played a major
role in enhancing the enzymatic digestibility of Eucalyptus in this study.
CONCLUSIONS: The two-step treatment with ionic liquids pretreatment and
successive alkali fractionation can be considered as a promising method to
improve the conversion of cellulose to glucose. The detailed information obtained
about chemical and anatomical changes was helpful to understand the underlying
mechanism of the integrated treatment process acting on Eucalyptus for enhancing
enzymatic digestibility.
PMID- 27499810
TI - Exploring xylose metabolism in Spathaspora species: XYL1.2 from Spathaspora
passalidarum as the key for efficient anaerobic xylose fermentation in metabolic
engineered Saccharomyces cerevisiae.
AB - BACKGROUND: The production of ethanol and other fuels and chemicals from
lignocellulosic materials is dependent of efficient xylose conversion. Xylose
fermentation capacity in yeasts is usually linked to xylose reductase (XR)
accepting NADH as cofactor. The XR from Scheffersomyces stipitis, which is able
to use NADH as cofactor but still prefers NADPH, has been used to generate
recombinant xylose-fermenting Saccharomyces cerevisiae. Novel xylose-fermenting
yeasts species, as those from the Spathaspora clade, have been described and are
potential sources of novel genes to improve xylose fermentation in S. cerevisiae.
RESULTS: Xylose fermentation by six strains from different Spathaspora species
isolated in Brazil, plus the Sp. passalidarum type strain (CBS 10155(T)), was
characterized under two oxygen-limited conditions. The best xylose-fermenting
strains belong to the Sp. passalidarum species, and their highest ethanol titers,
yields, and productivities were correlated to higher XR activity with NADH than
with NADPH. Among the different Spathaspora species, Sp. passalidarum appears to
be the sole harboring two XYL1 genes: XYL1.1, similar to the XYL1 found in other
Spathaspora and yeast species and XYL1.2, with relatively higher expression
level. XYL1.1p and XYL1.2p from Sp. passalidarum were expressed in S. cerevisiae
TMB 3044 and XYL1.1p was confirmed to be strictly NADPH-dependent, while XYL1.2p
to use both NADPH and NADH, with higher activity with the later. Recombinant S.
cerevisiae strains expressing XYL1.1p did not show anaerobic growth in xylose
medium. Under anaerobic xylose fermentation, S. cerevisiae TMB 3504, which
expresses XYL1.2p from Sp. passalidarum, revealed significant higher ethanol
yield and productivity than S. cerevisiae TMB 3422, which harbors XYL1p N272D
from Sc. stipitis in the same isogenic background (0.40 vs 0.34 g gCDW (-1) and
0.33 vs 0.18 g gCDW (-1) h(-1), respectively). CONCLUSION: This work explored a
new clade of xylose-fermenting yeasts (Spathaspora species) towards the
engineering of S. cerevisiae for improved xylose fermentation. The new S.
cerevisiae TMB 3504 displays higher XR activity with NADH than with NADPH, with
consequent improved ethanol yield and productivity and low xylitol production.
This meaningful advance in anaerobic xylose fermentation by recombinant S.
cerevisiae (using the XR/XDH pathway) paves the way for the development of novel
industrial pentose-fermenting strains.
PMID- 27499811
TI - 14q32.3-qter trisomic segment: a case report and literature review.
AB - BACKGROUND: Segmental duplication of the long arm of chromosome 14 (14q) has
commonly been reported to affect the proximal segment of 14q, while distal
duplication is a rare condition and often associated with segmental monosomy of
other chromosomes. CASE PRESENTATION: We report the clinical and genetic
characterization of a 4-year-old male patient with 14q32.3-qter trisomy resulting
from an adjacent segregation of a paternal reciprocal translocation
(14;21)(q32.1;p12). The child shows minor facial anomalies, severe developmental
delay, growth retardation, and a history of congenital hypothyroidism and
neonatal transitory hyperglycemic crises. CONCLUSIONS: To the best of our
knowledge, only 15 other cases of segmental 14q trisomy were documented. We
compared molecularly defined cases to identify a minimal common duplicated region
and to find genes with a hypothetical role in the phenotype. The presented case
supports the previous suggestion of a pure "distal 14q partial duplication" and
underlines the clinical variability.
PMID- 27499813
TI - SEX RATIO AT BIRTH AND THE IDEAL FAMILY IN CHI LINH DISTRICT, VIETNAM.
AB - Chi Linh district, which locates in the Red Delta River region, has been
recognized as the "hot pot" of high sex ratio at birth in Vietnam. This paper
used community-based periodic Demographic-Epidemiologic Surveillance System
(CHILILAB) to describe sex ratio at birth (SRB) and identify social - economic
factors that related to the SRB. A total 5,940 births born from August 1, 2004 to
August 31, 2011 was included in analysis. The SRB of 116.6 boys/100 girls (CI:
110.7 - 122.5) was significantly higher than normal. SRB were found high among
second child having only older sister(s), among third child and higher birth
order, among mothers who were 35 years and older, running small business or
homemakers. Interestingly, a SRB of 91.4 boys/100 girls (CI: 81.8 - 102) was
found among second children having an older brother, this is significantly lower
than the normal level. Further research should be done to assert if abortion is
practiced both to have a son and to have a daughter.
PMID- 27499812
TI - Cardiac Repair and Regeneration: The Value of Cell Therapies.
AB - Ischaemic heart disease is the predominant contributor to cardiovascular
morbidity and mortality; one million myocardial Infarctions occur per year in the
USA, while more than five million patients suffer from chronic heart failure.
Recently, heart failure has been singled out as an epidemic and is a staggering
clinical and public health problem associated with significant mortality,
morbidity and healthcare expenditures, particularly among those aged >=65 years.
Death rates have improved dramatically over the last four decades, but new
approaches are nevertheless urgently needed for those patients who go on to
develop ventricular dysfunction and chronic heart failure. Over the past decade,
stem cell transplantation has emerged as a promising therapeutic strategy for
acute or chronic ischaemic cardiomyopathy. Multiple candidate cell types have
been used in preclinical animal models and in humans to repair or regenerate the
injured heart, either directly or indirectly (through paracrine effects),
including: embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs),
neonatal cardiomyocytes, skeletal myoblasts (SKMs), endothelial progenitor cells,
bone marrow mononuclear cells (BMMNCs), mesenchymal stem cells (MSCs) and, most
recently, cardiac stem cells (CSCs). Although no consensus has emerged yet, the
ideal cell type for the treatment of heart disease should: (a) improve heart
function; (b) create healthy and functional cardiac muscle and vasculature,
integrated into the host tissue; (c) be amenable to delivery by minimally
invasive clinical methods; (d) be available 'off the shelf' as a standardised
reagent; (e) be tolerated by the immune system; (f) be safe oncologically, i.e.
not create tumours; and (g) circumvent societal ethical concerns. At present, it
is not clear whether such a 'perfect' stem cell exists; what is apparent,
however, is that some cell types are more promising than others. In this brief
review, we provide ongoing data on agreement and controversy arising from
clinical trials and touch upon the future directions of cell therapy for heart
disease.
PMID- 27499814
TI - Systematics, phylogeny, and taphonomy of ghost shrimps (Decapoda): a perspective
from the fossil record.
AB - Ghost shrimps of Callianassidae and Ctenochelidae are soft-bodied, usually
heterochelous decapods representing major bioturbators of muddy and sandy
(sub)marine substrates. Ghost shrimps have a robust fossil record spanning from
the Early Cretaceous (~ 133 Ma) to the Holocene and their remains are present in
most assemblages of Cenozoic decapod crustaceans. Their taxonomic interpretation
is in flux, mainly because the generic assignment is hindered by their
insufficient preservation and disagreement in the biological classification.
Furthermore, numerous taxa are incorrectly classified within the catch-all taxon
Callianassa. To show the historical patterns in describing fossil ghost shrimps
and to evaluate taphonomic aspects influencing the attribution of ghost shrimp
remains to higher level taxa, a database of all fossil species treated at some
time as belonging to the group has been compiled: 250 / 274 species are
considered valid ghost shrimp taxa herein. More than half of these taxa (160
species, 58.4%) are known only from distal cheliped elements, i.e., dactylus and
/ or propodus, due to the more calcified cuticle locally. Rarely, ghost shrimps
are preserved in situ in burrows or in direct association with them, and several
previously unpublished occurrences are reported herein. For generic assignment,
fossil material should be compared to living species because many of them have
modern relatives. Heterochely, intraspecific variation, ontogenetic changes and
sexual dimorphism are all factors that have to be taken into account when working
with fossil ghost shrimps. Distal elements are usually more variable than
proximal ones. Preliminary results suggest that the ghost shrimp clade emerged
not before the Hauterivian (~ 133 Ma). The divergence of Ctenochelidae and
Paracalliacinae is estimated to occur within the interval of Hauterivian to
Albian (133-100 Ma). Callichirinae and Eucalliacinae likely diverged later during
the Late Cretaceous (100-66 Ma), whereas Callianassinae did not appear before the
Eocene (56 Ma).
PMID- 27499816
TI - Comparing Sexuality Communication Among Offspring of Teen Parents and Adult
Parents: a Different Role for Extended Family.
AB - This brief report examined teenagers' sexuality communication with their parents
and extended families. It compared who teens of early parents (those who had
children when they were adolescents) and teens of later parents (those who were
adults when they had children) talk to about sex. Eighth grade students (N=1281)
in 24 schools completed survey items about their communication about sex.
Structural equation modeling was used to predict communication profiles, while
adjusting for the nesting of students within schools. After controlling for
teens' age, gender, race/ethnicity, grades, parent/guardian closeness, and social
desirability of survey responses, as well as family status and median family
income, results showed that teens of early (teen) parents were more likely than
teens of later (adult) parents to talk with both parents and extended family
about sex and less likely than later parents to talk only with parents. These
findings indicate that realities of teen sexuality communication for teens of
early parents may extend beyond a parent-teen model to include extended family.
Extended family involvement in educational outreach is a potential untapped
resource to support sexual health for teens of early parents.
PMID- 27499815
TI - LINCing defective nuclear-cytoskeletal coupling and DYT1 dystonia.
AB - Mechanical forces generated by nuclear-cytoskeletal coupling through the LINC
(linker of nucleoskeleton and cytoskeleton) complex, an evolutionarily conserved
molecular bridge in the nuclear envelope (NE), are critical for the execution of
wholesale nuclear positioning events in migrating and dividing cells, chromosome
dynamics during meiosis, and mechanotransduction. LINC complexes consist of outer
(KASH (Klarsicht, ANC-1, and Syne homology)) and inner (SUN (Sad1, UNC-84))
nuclear membrane proteins. KASH proteins interact with the cytoskeleton in the
cytoplasm and SUN proteins in the perinuclear space of the NE. In the
nucleoplasm, SUN proteins interact with A-type nuclear lamins and chromatin
binding proteins. Recent structural insights into the KASH-SUN interaction have
generated several questions regarding how LINC complex assembly and function
might be regulated within the perinuclear space. Here we discuss potential LINC
regulatory mechanisms and focus on the potential role of AAA+ (ATPases associated
with various cellular activities) protein, torsinA, as a LINC complex regulator
within the NE. We also examine how defects in LINC complex regulation by torsinA
may contribute to the pathogenesis of the human neurological movement disorder,
DYT1 dystonia.
PMID- 27499817
TI - Cardiac Dual-source Computed Tomography for the Detection of Left Main
Compression Syndrome in Patients with Pulmonary Hyper-tension.
AB - INTRODUCTION: Left Main Compression Syndrome (LMCS) represents an entity
described as the extrinsic compression of the left main coronary artery (LMCA) by
a dilated pulmonary artery (PA) trunk. We examined the presence of LMCS in
patients with pulmonary hypertension (PH) using dual-source computed tomography
(DSCT), as a non-invasive diagnostic tool. METHODS: The following parameters were
measured: PA trunk diameter (PAD), the distance between PAD and LMCA (LMPA) and
the distance between PA and aorta (AoPA). These measurements were related with
demographic, echocardiographic, hemodynamic and clinical parameters. Angiography
was performed in two patients with LMCS suspected by cardiac computed tomographic
angiography. Patients without PH but with angina were examined as controls, using
DSCT cardiac angiography to assess the same measurements and to detect the
prevalence of coronary artery disease. RESULTS: PA diameter value over 40.00 mm
has been associated with PH and LMCS. Furthermore, LMCS did not occur at a
distance smaller than 0.50 mm between the PA and the LMCA, and did not correlate
with the distance between the PA and the aorta or with cardiac index and NT
proBNP. CONCLUSION: DSCT may represent the initial testing modality in PH
patients with dilated PA trunk to exclude LMCS. A periodical rule-out of this
rare entity, as assessed by DSCT, in patients with a severely dilated PA seems to
be mandatory for PH patients contributing to survival improvement.
PMID- 27499818
TI - Allogeneic Blood Product Usage in Coronary Artery Bypass Grafting (CABG) with
minimalized Extracorporeal Circulation System (MECC) Versus Standard On-Pump
Coronary Artery Bypass Grafting.
AB - AIM: Intraoperative allogeneic blood product transfusion (ABPT) in cardiac
surgery is associated with worse overall outcome, including mortality. The
objective of this study was to evaluate the ABPTs in minimalized extracorporeal
cardiopulmonary (MECC(TM)) compared with standard open system on-pump coronary
revascularization. METHODS: Data of 156 patients undergoing myocardial
revascularization between September 2008 and September 2010 were reviewed. 83
patients were operated by the MECC technique and 73 were treated by standard
extracorporeal circulation (sECC). ABPT and overall early postoperative
complications were analyzed. RESULTS: Operative mortality and morbidity were
similar in both groups. ABPT in the MECC group was significantly lower than in
the sECC group both intraoperatively (7.2 vs. 60.3% of patients p<0.001) and
during the first five postoperative days (19.3 vs. 57.5%; p<0.001). "Skin to
skin"- (214 +/- 45 vs. 232 +/- 45 min; p=0.012), cardiopulmonary bypass (CPB) -
(82 +/- 25 vs. 95 +/- 26 min; p=0.014), and X-clamp- times (50 +/- 16 vs. 56 +/-
17 min; p=0.024) were significantly lower in the MECC group than in the sECC
group. Length of ICU (intensive care unit) - and hospital stay were also
significantly lower in the MECC group vs. the sECC group (26.7 +/- 20.2 vs. 54.5
+/- 68.9 h; p<0.001, and 12.0 +/- 4.1 vs. 14.5 +/- 4.6 days; p<0.001).
CONCLUSION: Application of MECC as on-pump coronary artery bypass graft (CABG)
results in significantly lower ABPT as well as shorter ICU and in-hospital stay.
In order to achieve these benefits of MECC autologous retrograde priming,
Bispectral index (BIS) monitoring, intraoperative cell salvage, meticulous
hemostasis and strict peri- and postoperative volume management are crucial.
PMID- 27499819
TI - Child Abuse Syndrome (CAS): A Newly Recognized Distinct Entity.
PMID- 27499820
TI - Efficacy and Safety of Modified Pranlukast (Prakanon((r))) Compared with
Pranlukast (Onon((r))): A Randomized, Open-Label, Crossover Study.
AB - INTRODUCTION: Pranlukast is a leukotriene receptor antagonist (LTRA) that is used
as an additional controller of mild to moderate asthma. This study compared the
efficacy and side effects of two bioequivalent preparations of pranlukast:
original pranlukast (Onon((r)); Ono Pharmaceutical, Japan) and a modified
formulation of pranlukast (Prakanon((r)); Yuhan Co, Korea) in patients with mild
to moderate asthma. METHODS: Of the 34 subjects screened, 30 patients who were
using standard medication to control asthma and scored less than 20 points on the
Asthma Control Test(TM) (ACT) were assigned randomly to one of the two groups in
a prospective, open label, crossover study: group 1 received Prakanon((r)) (150
mg/day) and group 2 received Onon((r)) (450 mg/day) for 8 weeks each; after a 1
week rest period, the groups were switched to the alternative medication for
further 8 weeks and monitored for 2 more weeks without study medication.
Evaluation parameters included the ACT, quality of life questionnaire adult
Korean asthmatics (QLQAKA), pulmonary function tests, peripheral blood tests,
vital signs, and adverse events. RESULTS: Thirty patients were enrolled and 21
completed the trial: 10 in group 1 and 11 in group 2. The baseline data of the
two groups did not differ. No statistical significant differences were observed
in efficacy and lung function at each time and in changes from baseline value
between the two kinds of pranlukast. The final asthma control rate was 81% with
Prakanon((r)) and 76% with Onon((r)). There were no differences in vital signs
and laboratory data at each time and in changes from baseline value between the
two drugs. There were no differences in adverse events between the two drugs. The
most common side effect was abdominal pain. Drug compliance was high, without
differences between the two drugs. CONCLUSION: These findings suggest that
Prakanon((r)) which is an improved formulation of pranlukast at a lower dose than
the original formulation, Onon((r)), has a similar efficacy and side effect
profile in the control of persistent asthma.
PMID- 27499821
TI - Pilot Study of a New Adjustable Thermoplastic Mandibular Advancement Device for
the Management of Obstructive Sleep Apnoea-Hypopnoea Syndrome: A Brief Research
Letter.
AB - BACKGROUND: Prefabricated adjustable thermoplastic mandibular advancement devices
(PAT-MADs) are a practical short-term treatment for obstructive sleep apnoea
hypopnoea syndrome (OSAHS) in patients who have failed or refused continuous
positive airway pressure (CPAP) therapy. OBJECTIVE: To assess the effectiveness
of a new professionally-fitted PAT-MAD in patients with OSAHS in Morocco. METHOD:
Twenty-four adults with mild, moderate or severe OSAHS were fitted with the PAT
MAD (BluePro((r)); BlueSom, France). Respiratory parameters (apnoea-hypopnoea
index (AHI), oxygen desaturation index (ODI)) and daytime sleepiness using the
Epworth Sleepiness scale (ESS) were assessed before and after treatment. Adverse
events were recorded. RESULTS: Mean treatment duration was 106.3 +/- 73.4 days.
Mean AHI score decreased from 21.4 +/- 7.4 to 9.3 +/- 4.1 after treatment
(p<0.0001) (mean reduction of 57.0 +/- 12.3%). Mean ESS and ODI also decreased at
EOS (from 10.4 +/- 2.8 to 7.3 +/- 2.3, mean reduction 30.3 +/- 12.2%, p=0.0001;
and 7.0 +/- 6.9 to 4.7 +/- 4.0, mean reduction 30.5 +/- 25.0%, p=0.2,
respectively). Treatment was considered to have been successful in 22 patients
(91.7%) who had mild OSAHS or an AHI score of <=5 at the end of the study. The
device was well-tolerated. CONCLUSION: This new PAT-MAD appears to be effective
at reducing respiratory parameters and improving daytime alertness in patients
with OSAHS. Long term studies in a larger number of patients are warranted to
assess the long-term efficacy, retention and side-effects of this device.
PMID- 27499823
TI - Incidence of Venous Thromboembolism in Patients Undergoing Major Hip Surgeries at
a Single Institution: A Prospective Study.
AB - BACKGROUND: Venous thoromboembolism (VTE) is one of the most significant
complications after hip surgeries. Many studies have been reported about the
incidence of VTE after THA, but a small number of reports were found concerning
Periacetabular osteotomy, Revision THA and Surgery for hip fracture
postoperatively. Furthermore, there exists no comparative study of the incidence
of VTE among major hip surgeries at a single institution. We reported the
incidence of VTE among hip surgeries performed at a single institution. METHODS:
A total of 820 Hip surgeries were performed at same institution. The procedures
included 420 hips that underwent primary total hip arthroplasties (THA), 91
revision or removal of total hip arthroplasties (Revision THA), 144
periacetabular osteotomy (PAO) and 165 surgery for hip fracture (SHF) between
2006 and 2012. VTE was detected by Multidetector computed tomography (MDCT) that
scanned 768 cases and by ultrasound that scanned 52cases postoperative 10-14
days. RESULTS: The overall incidence of VTE was 12.2% (100 of 820). The incidence
of VTE after THA was 13.1% (55 of 420), Revision THA was 13.2% (12 of 91), PAO
was 2.1% (3 of 144) and SHF was 18.1% (30 of 165). The incidence of VTE was
significantly higher in SHF than in PAO. CONCLUSION: This data indicates that the
incidence of VTE after PAO is significantly lower than SHF and relatively lower
than THA and Revision THA. A younger age and non-invasion of the bone marrow of
the femur may have affected the result. Prophylaxis therapy was effective
especially on SHF.
PMID- 27499822
TI - Particle Disease: A Current Review of the Biological Mechanisms in Periprosthetic
Osteolysis After Hip Arthroplasty.
AB - BACKGROUND: Inflammatory responses to wear debris cause osteolysis that leads to
aseptic prosthesis loosening and hip arthroplasty failure. Although osteolysis is
usually associated with aseptic loosening, it is rarely seen around stable
implants. Aseptic implant loosening is a simple radiologic phenomenon, but a
complex immunological process. Particulate debris produced by implants most
commonly causes osteolysis, and this is called particle-associated periprosthetic
osteolysis (PPO). OBJECTIVE: The objective of this review is to outline the
features of particle-associated periprosthetic osteolysis to allow the physician
to recognise this condition and commence early treatment, thereby optimizing
patient outcome. METHODS: A thorough literature search was performed using
available databases, including Pubmed, to cover important research published
covering particle-associated PPO. RESULTS: Although osteolysis causes bone
resorption, clinical, animal, and in vitro studies of particle bioreactivity
suggest that particle-associated PPO represents the culmination of several
biological reactions of many cell types, rather than being caused solely by the
osteoclasts. The biological activity is highly dependent on the characteristics
and quantity of the wear particles. CONCLUSION: Despite advances in total hip
arthroplasty (THA), particle-associated PPO and aseptic loosening continue to be
major factors that affect prosthetic joint longevity. Biomarkers could be
exploited as easy and objective diagnostic and prognostic targets that would
enable testing for osteolysis after THA. Further research is needed to identify
new biomarkers in PPO. A comprehensive understanding of the underlying biological
mechanisms is crucial for developing new therapeutic interventions to reverse or
suppress biological responses to wear particles.
PMID- 27499824
TI - Primary Intracranial Choriocarcinoma Located in the Suprasellar Region.
AB - A 10 year old girl was admitted to our hospital due to headache, nausea, and
weight loss for about half a year. She also had visual field disorders.
Suprasellar tumor was found by X-ray computed tomography, and magnetic resonance
imaging showed a ring-like lobulated enhanced mass with hemorrhage and necrosis.
Biopsy of this lesion showed primary intracranial choriocarcinoma on
histopathological examination. The serum human chorionic gonadotropin (hCG) level
was measured after the biopsy and was elevated at 71,298.2 IU/L. The patient died
due to hydrocephalus caused by an increase in the size of the tumor with a larger
amount of hemorrhage than the preoperative features. If young patients present
with a suprasellar lobulated mass with hemorrhage, the serum hCG level should be
measured before operation.
PMID- 27499826
TI - A Neurotized Anterolateral Thigh Flap With a Unique Anastomosis to the
Gastroepiploic Artery: A Case Report of a Reconstruction of Composite Abdominal
Wall Defect.
PMID- 27499825
TI - Recurrent urinary tract infections in healthy and nonpregnant women.
AB - Recurrent urinary tract infections (RUTI) are prevalent and pose significant
clinical challenges. Although the term RUTI has long been vaguely defined, a
consensus definition has emerged in recent years. The exact etiology behind RUTI
remains under debate, with valid arguments for both ascending reinfections as
well as persistent infection inside the bladder. These persistent infections
exist in the form of quiescent intracellular reservoirs in the mouse model and
may represent a novel concept to explain UTI recurrence in humans. Manageable
risk factors such as behavioral patterns alongside nonmanageable risk factors
including genetic susceptibility are growing fields of investigation. Acute UTI
have been studied through two model bacterial strains: Escherichia coli UTI89 and
CFT073. However, the clinical relevance to RUTI of these two strains has not been
firmly established. Current treatment strategies for RUTI are limited and remain
dominated by antibiotic usage despite variable efficacy. The majority of studies
in humans have focused on younger groups of women with little information
available about the postmenopausal population despite a heightened risk of RUTI
in this age group.
PMID- 27499827
TI - Draft genomic sequence of a chromate- and sulfate-reducing Alishewanella strain
with the ability to bioremediate Cr and Cd contamination.
AB - Alishewanella sp. WH16-1 (= CCTCC M201507) is a facultative anaerobic, motile,
Gram-negative, rod-shaped bacterium isolated from soil of a copper and iron mine.
This strain efficiently reduces chromate (Cr(6+)) to the much less toxic Cr(3+).
In addition, it reduces sulfate (SO4 (2-)) to S(2-). The S(2-) could react with
Cd(2+) to generate precipitated CdS. Thus, strain WH16-1 shows a great potential
to bioremediate Cr and Cd contaimination. Here we describe the features of this
organism, together with the draft genome and comparative genomic results among
strain WH16-1 and other Alishewanella strains. The genome comprises 3,488,867 bp,
50.4 % G + C content, 3,132 protein-coding genes and 80 RNA genes. Both putative
chromate- and sulfate-reducing genes are identified.
PMID- 27499828
TI - MORPHOMETRIC ANALYSIS OF HIPPOCAMPUS AND LATERAL VENTRICLE REVEALS REGIONAL
DIFFERENCE BETWEEN COGNITIVELY STABLE AND DECLINING PERSONS.
AB - Alzheimers disease (AD) is a progressive neurodegenerative disease most prevalent
in the elderly. Distinguishing disease-related memory decline from normal age
related memory decline has been clinically difficult due to the subtlety of
cognitive change during the preclinical stage of AD. In contrast, sensitive
biomarkers derived from in vivo neuroimaging data could improve the early
identification of AD. In this study, we employed a morphometric analysis in the
hippocampus and lateral ventricle. A novel group-wise template-based segmentation
algorithm was developed for ventricular segmentation. Further, surface
multivariate tensor-based morphometry and radial distance on each surface point
were computed. Using Hotellings T2 test, we found significant morphometric
differences in both hippocampus and lateral ventricle between stable and
clinically declining subjects. The left hemisphere was more severely affected
than the right during this early disease stage. Hippocampal and ventricular
morphometry has significant potential as an imaging biomarker for onset
prediction and early diagnosis of AD.
PMID- 27499829
TI - APPLYING SPARSE CODING TO SURFACE MULTIVARIATE TENSOR-BASED MORPHOMETRY TO
PREDICT FUTURE COGNITIVE DECLINE.
AB - Alzheimer's disease (AD) is a progressive brain disease. Accurate diagnosis of AD
and its prodromal stage, mild cognitive impairment, is crucial for clinical trial
design. There is also growing interests in identifying brain imaging biomarkers
that help evaluate AD risk presymptomatically. Here, we applied a recently
developed multivariate tensor-based morphometry (mTBM) method to extract features
from hippocampal surfaces, derived from anatomical brain MRI. For such surface
based features, the feature dimension is usually much larger than the number of
subjects. We used dictionary learning and sparse coding to effectively reduce the
feature dimensions. With the new features, an Adaboost classifier was employed
for binary group classification. In tests on publicly available data from the
Alzheimers Disease Neuroimaging Initiative, the new framework outperformed
several standard imaging measures in classifying different stages of AD. The new
approach combines the efficiency of sparse coding with the sensitivity of surface
mTBM, and boosts classification performance.
PMID- 27499830
TI - Video capsule endoscopy in inflammatory bowel disease.
AB - Video capsule endoscopy (VCE) has evolved to become an important tool for the non
invasive examination of the small bowel, which hitherto had been relatively
inaccessible to direct visualisation. VCE has been shown to play a role in
monitoring the activity of small bowel Crohn's disease and can be used to assess
the response to anti-inflammatory treatment in Crohn's disease. For those
patients with Crohn's disease who have undergone an intestinal resection, VCE has
been assessed as a tool to detect post-operative recurrence. VCE may also aid in
the reclassification of patients with a diagnosis of Inflammatory Bowel Disease
Unclassified to Crohn's disease. The evolution of colon capsule endoscopy (CCE)
has expanded the application of this technology further. The use of CCE to assess
the activity of ulcerative colitis has been described. This advance in capsule
technology has also fuelled interest in its potential role as a minimally
invasive tool to assess the whole of GI tract opening the possibility of its use
for the panenteric assessment of Crohn's disease. VCE is a safe procedure.
However, the risk of a retained capsule is higher in patients with suspected or
confirmed Crohn's disease compared with patients having VCE examination for other
indications. A retained video capsule is rare after successful passage of a
patency capsule which may be utilised to pre-screen patients undergoing VCE. This
paper describes the use of VCE in the assessment of inflammatory bowel disease.
PMID- 27499831
TI - Endoscopic full thickness resection for gastric tumors originating from
muscularis propria.
AB - AIM: To do systematic review of current literature for endoscopic full thickness
resection (EFTR) technique for gastric tumors originating from muscularis
propria. METHODS: An extensive English literature search was done till December
2015; using PubMed and Google scholar to identify the peer reviewed original and
review articles using keywords-EFTR, gastric tumor, muscularis propria. Human
only studies were included. The references of pertinent studies were manually
searched to identify additional relevant studies. The indications, procedural
details, success rates, clinical outcomes, complications and limitations were
considered. For the purpose of review, data from individual studies was combined
to calculate mean. No other statistical test was applied. RESULTS: A total of 9
original articles were identified. Four articles were from same institute and the
time frames of these studies were overlapping. To avoid duplication of data, only
the study with patients over the longest time interval was included and other
three were excluded. In total six studies were included in the final review. In
our systematic review, the mean success rate for EFTR of gastric tumors
originating from muscularis propria was 96.8%. The mean procedure time varied
from a minimum of 37 min to a maximum of 105 min. There was no reported mortality
from the technique itself. The most common histological diagnosis was
gastrointestinal stromal tumors and leiomyoma. Gastric wall defect closure by
either metallic clips or over the scope clip (OTSC) had similar outcomes although
experience with OTSC was limited to smaller lesions (< 3 cm). CONCLUSION: EFTR is
a minimally invasive technique to resect gastric submucosal tumors originating
from muscularis propria with a high success rate and low complication rate.
PMID- 27499832
TI - Splenic artery aneurysm presenting as a submucosal gastric lesion: A case report.
AB - We are reporting the rare case of splenic artery aneurysm of 4 cm of diameter
presenting as a sub mucosal lesion on gastro-duodenal endoscopy. This aneurysm
was treated by endovascular coil embolization and stent graft implantation. The
procedure was uneventful. On day 1, the patient presented an acute severe
epigastric pain and cardiovascular arrest. Abdominal computed tomography scan
showed an active leak of the intravenous contrast dye in the peritoneum from the
splenic aneurysm. We performed an emergent resection of the aneurysm, and
peritoneal lavage. Postoperatively, hemorrhagic choc was refractory to large
volumes replacement, and intravenous vaso-active drugs. On day 2, he presented
massive hematochezia. We performed a total colectomy with splenectomy and
cholecystectomy for ischemic colitis, with spleen and gallbladder infarction.
Despite vaso-active drugs and aggressive treatment with Factor VIIa, the patient
died after uncontrolled disseminated intravascular coagulation.
PMID- 27499833
TI - A Literature Review: Website Design and User Engagement.
AB - Proper design has become a critical element needed to engage website and mobile
application users. However, little research has been conducted to define the
specific elements used in effective website and mobile application design. We
attempt to review and consolidate research on effective design and to define a
short list of elements frequently used in research. The design elements mentioned
most frequently in the reviewed literature were navigation, graphical
representation, organization, content utility, purpose, simplicity, and
readability. We discuss how previous studies define and evaluate these seven
elements. This review and the resulting short list of design elements may be used
to help designers and researchers to operationalize best practices for
facilitating and predicting user engagement.
PMID- 27499834
TI - 'I Haue Ben Crised and Besy': Illness and Resilience in the Fifteenth-Century
Stonor Letters.
AB - The modern and medieval meanings of words reporting ill health often bear little
resemblance to one another. This article compares the use of 'diseased' and
'sick' in the fifteenth-century Stonor family letters. It examines the word
'crased', which implies physical ill health most directly, but also suggests
emotional, psychological, or spiritual distress in female family members
especially. The article then turns to the practical implications of poor health,
asking how and why it affected the day-to-day concerns of the Stonors and their
associates. It uncovers compelling evidence for resilience in the face of many
and competing calls of duty. Finally, the article presents unique palaeographical
evidence for the impact of illness, where a correspondent is so 'seke' that he
can scarcely hold his pen.
PMID- 27499835
TI - Recurrent Syncope and Cardiac Arrest in a Patient with Systemic Light Chain
Amyloidosis Treated with Bortezomib.
AB - About 10-15% of patients with multiple myeloma develop light chain (AL)
amyloidosis. AL amyloidosis is a systemic disease that may involve multiple
organs, often including the heart. It may present clinically with bradyarrhythmia
and syncope. The proteasome inhibitor bortezomib has been used with clinical
efficacy in treating patients with AL amyloidosis but also implicated as a
possible cause of cardiomyocyte injury. We report a case of a 48-year-old man
with AL amyloidosis and increased frequency of syncope and cardiac arrest after
starting bortezomib. The biologic and clinical plausibility of a heightened risk
for cardiac arrest in patients with cardiac AL amyloidosis and history of syncope
being treated with bortezomib is a possibility that is not well documented in the
medical literature and warrants further investigation.
PMID- 27499836
TI - CD30+ Primary Cutaneous Post-transplant Lymphoproliferative Disorder with Signet
ring Cell Features.
AB - We report a case of primary cutaneous CD30+ post-transplant lymphoproliferative
disorder with an uncommon finding of signet ring cell features in a heart
transplant patient. The neoplastic cells were CD4 and CD30 positive, and negative
for S-100, pancytokeratin, myeloperoxidase, and CD56. In situ hybridization for
Epstein Barr Virus (EBV) was negative, even though the patient did have EBV
viremia.
PMID- 27499837
TI - Autoimmune Syndromes Presenting as a Paraneoplastic Manifestation of
Myelodysplastic Syndromes: Clinical Features, Course, Treatment and Outcome.
AB - Autoimmune manifestations (AIM) are reported in up to 10-30% of myelodysplastic
syndromes (MDS) patients; this association is not well defined. We present herein
a retrospective chart review of single center MDS patients for AIM, a case
discussion and a literature review. Of 252 MDS patients examined, 11 (4.4%) had
AIM around MDS diagnosis. International Prognostic Scoring System scores were:
low or intermediate (int)-1 (n=7); int-2 or high (n=4). AIM were: culture
negative sepsis (n=7); inflammatory arthritis (n=3); vasculitis (n=4); sweats;
pericarditis; polymyalgia rheumatica (n=2 each); mouth ulcers; pulmonary
infiltrates; suspicion for Behcet's; polychondritis and undifferentiated (n=1
each). AIM treatment and outcome were: prednisone +/- steroid sparing agents,
n=8, ongoing symptoms in 5; azacitidine (n=3), 2 resolved; and observation, n=1,
ongoing symptoms. At a median follow up of 13 months, seven patients are alive.
In summary, 4.4% of MDS patients presented with concomitant AIM. MDS should
remain on the differential diagnosis of patients with inflammatory symptoms.
PMID- 27499838
TI - Refractory Ascites with Liver Fibrosis Developed in Late Phase Allogeneic
Hematopoietic Stem Cell Transplantation: Report of Three Patients.
AB - We report cases of three patients of refractory ascites without other fluid
retention that occurred around five months after allogeneic hematopoietic stem
cell transplantation (allo-HSCT). All three patients expired and postmortem
examinations revealed unexpected liver fibrosis lacking histological evidences of
graft-versus-host-disease (GVHD). The three patients showed normal hepatic
function and size before transplantation. During their clinical courses, serum
biochemistry test showed no elevation of hepatic enzymes and bilirubin; however,
imaging studies demonstrated hepatic atrophy at the onset of ascites. One of the
liver specimens showed bile obstruction, which could be seen in hepatic damage by
GVHD. Although ascites resulting from venoocclusive disease in early phase allo
HSCT is well documented, ascites associated with hepatic fibrosis in late phase
allo-HCST has not been reported. Further clinico-pathological studies on similar
patients should be required to ascertain refractory ascites associated with liver
fibrosis after allo-HSCT.
PMID- 27499839
TI - Shedding light on the 'dark side' of phylogenetic comparative methods.
AB - Phylogenetic comparative methods are becoming increasingly popular for
investigating evolutionary patterns and processes. However, these methods are not
infallible - they suffer from biases and make assumptions like all other
statistical methods.Unfortunately, although these limitations are generally well
known in the phylogenetic comparative methods community, they are often
inadequately assessed in empirical studies leading to misinterpreted results and
poor model fits. Here, we explore reasons for the communication gap dividing
those developing new methods and those using them.We suggest that some important
pieces of information are missing from the literature and that others are
difficult to extract from long, technical papers. We also highlight problems with
users jumping straight into software implementations of methods (e.g. in r) that
may lack documentation on biases and assumptions that are mentioned in the
original papers.To help solve these problems, we make a number of suggestions
including providing blog posts or videos to explain new methods in less technical
terms, encouraging reproducibility and code sharing, making wiki-style pages
summarising the literature on popular methods, more careful consideration and
testing of whether a method is appropriate for a given question/data set,
increased collaboration, and a shift from publishing purely novel methods to
publishing improvements to existing methods and ways of detecting biases or
testing model fit. Many of these points are applicable across methods in ecology
and evolution, not just phylogenetic comparative methods.
PMID- 27499840
TI - Refining the Enrolment Process in Emergency Medicine Research.
AB - Research in the emergency setting involving patients with acute clinical
conditions is needed if there are to be advances in diagnosis and treatment. But
research in these areas poses ethical and practical challenges. One of these is
the general inability to obtain informed consent due to the patient's lack of
mental capacity and insufficient time to contact legal representatives.
Regulatory frameworks which allow this research to proceed with a consent
'waiver', provided patients lack mental capacity, miss important ethical
subtleties. One of these is the varying nature of mental capacity among emergency
medicine patients. Not only is their capacity variable and often unclear, but
some patients are also likely to be able to engage with the researcher and the
context to varying degrees. In this paper we describe the key elements of a novel
enrolment process for emergency medicine research that refines the consent waiver
and fully engages with the ethical rationale for consent and, in this context,
its waiver. The process is verbal but independently documented during the
'emergent' stages of the research. It provides appropriate engagement with the
patient, is context-sensitive and better addresses ethical subtleties. In line
with regulation, full written consent for on-going participation in the research
is obtained once the emergency is passed.
PMID- 27499841
TI - Droplet-based microfluidics for artificial cell generation: a brief review.
AB - Artificial cells are best defined as micrometre-sized structures able to mimic
many of the morphological and functional characteristics of a living cell. In
this mini-review, we describe progress in the application of droplet-based
microfluidics for the generation of artificial cells and protocells.
PMID- 27499842
TI - Single mode waveguide platform for spontaneous and surface-enhanced on-chip Raman
spectroscopy.
AB - We review an on-chip approach for spontaneous Raman spectroscopy and surface
enhanced Raman spectroscopy based on evanescent excitation of the analyte as well
as evanescent collection of the Raman signal using complementary metal oxide
semiconductor (CMOS)-compatible single mode waveguides. The signal is either
directly collected from the analyte molecules or via plasmonic nanoantennas
integrated on top of the waveguides. Flexibility in the design of the geometry of
the waveguide, and/or the geometry of the antennas, enables optimization of the
collection efficiency. Furthermore, the sensor can be integrated with additional
functionality (sources, detectors, spectrometers) on the same chip. In this
paper, the basic theoretical concepts are introduced to identify the key design
parameters, and some proof-of-concept experimental results are reviewed.
PMID- 27499843
TI - Adaptation of sensor morphology: an integrative view of perception from
biologically inspired robotics perspective.
AB - Sensor morphology, the morphology of a sensing mechanism which plays a role of
shaping the desired response from physical stimuli from surroundings to generate
signals usable as sensory information, is one of the key common aspects of
sensing processes. This paper presents a structured review of researches on
bioinspired sensor morphology implemented in robotic systems, and discusses the
fundamental design principles. Based on literature review, we propose two key
arguments: first, owing to its synthetic nature, biologically inspired robotics
approach is a unique and powerful methodology to understand the role of sensor
morphology and how it can evolve and adapt to its task and environment. Second, a
consideration of an integrative view of perception by looking into
multidisciplinary and overarching mechanisms of sensor morphology adaptation
across biology and engineering enables us to extract relevant design principles
that are important to extend our understanding of the unfinished concepts in
sensing and perception.
PMID- 27499844
TI - Development of an open technology sensor suite for assisted living: a student-led
research project.
AB - Many countries have a rapidly ageing population, placing strain on health
services and creating a growing market for assistive technology for older people.
We have, through a student-led, 12-week project for 10 students from a variety of
science and engineering backgrounds, developed an integrated sensor system to
enable older people, or those at risk, to live independently in their own homes
for longer, while providing reassurance for their family and carers. We provide
details on the design procedure and performance of our sensor system and the
management and execution of a short-term, student-led research project. Detailed
information on the design and use of our devices, including a door sensor, power
monitor, fall detector, general in-house sensor unit and easy-to-use location
aware communications device, is given, with our open designs being contrasted
with closed proprietary systems. A case study is presented for the use of our
devices in a real-world context, along with a comparison with commercially
available systems. We discuss how the system could lead to improvements in the
quality of life of older users and increase the effectiveness of their associated
care network. We reflect on how recent developments in open source technology and
rapid prototyping increase the scope and potential for the development of
powerful sensor systems and, finally, conclude with a student perspective on this
team effort and highlight learning outcomes, arguing that open technologies will
revolutionize the way in which technology will be deployed in academic research
in the future.
PMID- 27499845
TI - Infrastructure sensing.
AB - Design, construction, maintenance and upgrading of civil engineering
infrastructure requires fresh thinking to minimize use of materials, energy and
labour. This can only be achieved by understanding the performance of the
infrastructure, both during its construction and throughout its design life,
through innovative monitoring. Advances in sensor systems offer intriguing
possibilities to radically alter methods of condition assessment and monitoring
of infrastructure. In this paper, it is hypothesized that the future of
infrastructure relies on smarter information; the rich information obtained from
embedded sensors within infrastructure will act as a catalyst for new design,
construction, operation and maintenance processes for integrated infrastructure
systems linked directly with user behaviour patterns. Some examples of emerging
sensor technologies for infrastructure sensing are given. They include
distributed fibre-optics sensors, computer vision, wireless sensor networks, low
power micro-electromechanical systems, energy harvesting and citizens as sensors.
PMID- 27499846
TI - Electroactive polymers for sensing.
AB - Electromechanical coupling in electroactive polymers (EAPs) has been widely
applied for actuation and is also being increasingly investigated for sensing
chemical and mechanical stimuli. EAPs are a unique class of materials, with low
moduli high-strain capabilities and the ability to conform to surfaces of
different shapes. These features make them attractive for applications such as
wearable sensors and interfacing with soft tissues. Here, we review the major
types of EAPs and their sensing mechanisms. These are divided into two classes
depending on the main type of charge carrier: ionic EAPs (such as conducting
polymers and ionic polymer-metal composites) and electronic EAPs (such as
dielectric elastomers, liquid-crystal polymers and piezoelectric polymers). This
review is intended to serve as an introduction to the mechanisms of these
materials and as a first step in material selection for both researchers and
designers of flexible/bendable devices, biocompatible sensors or even robotic
tactile sensing units.
PMID- 27499847
TI - Metal-organic frameworks as biosensors for luminescence-based detection and
imaging.
AB - Metal-organic frameworks (MOFs), formed by the self-assembly of metal centres or
clusters and organic linkers, possess many key structural and chemical features
that have enabled them to be used in sensing platforms for a variety of
environmentally, chemically and biomedically relevant compounds. In particular,
their high porosity, large surface area, tuneable chemical composition, high
degree of crystallinity, and potential for post-synthetic modification for
molecular recognition make MOFs promising candidates for biosensing applications.
In this review, we separate our discussion of MOF biosensors into two categories:
quantitative sensing, focusing specifically on luminescence-based sensors for the
direct measurement of a specific analyte, and qualitative sensing, where we
describe MOFs used for fluorescence microscopy and as magnetic resonance imaging
contrast agents. We highlight several key publications in each of these areas,
concluding that MOFs present an exciting, versatile new platform for biosensing
applications and imaging, and we expect to see their usage grow as the field
progresses.
PMID- 27499848
TI - Children view own-age faces qualitatively differently to other-age faces.
AB - Like most own-group biases in face recognition, the own-age bias (OAB) is thought
to be based either on perceptual expertise or socio-cognitive motivational
mechanisms [Wolff, N., Kemter, K., Schweinberger, S. R., & Wiese, H. (2013). What
drives social in-group biases in face recognition memory? ERP evidence from the
own-gender bias. Social Cognitive and Affective Neuroscience.
doi:10.1093/scan/nst024]. The present study employed a recognition paradigm with
eye-tracking in order to assess whether participants actively viewed faces of
their own-age differently to that of other-age faces. The results indicated a
significant OAB (superior recognition for own-age relative to other-age faces),
provided that they were upright, indicative of expertise being employed for the
recognition of own-age faces. However, the eye-tracking results indicate that
viewing other-age faces was qualitatively different to the viewing of own-age
faces, with more nose fixations for other-age faces. These results are
interpreted as supporting the socio-cognitive model of the OAB.
PMID- 27499850
TI - From hepatoprotection models to new therapeutic modalities for treating liver
diseases: a personal perspective.
AB - A variety of rodent models of hepatoprotection have been developed in which
tolerance to acetaminophen-induced hepatotoxicity occurs.
Autoprotection/heteroprotection is a phenomenon where prior exposure to a mildly
toxic dose of toxicant confers protection against a subsequently administered
higher dose of the same toxicant (as in the case of autoprotection) or to a
different toxicant (referred to as heteroprotection). Multiple mechanisms
regulate this adaptive response, including hepatocellular proliferation,
proteostasis, enhanced expression of cytoprotective genes, and altered tissue
immune response. In this review, we will discuss recent findings that highlight
the complexity of these adaptive mechanisms and we also outline the usefulness of
these findings to devise therapeutic and/or diagnostic tools for acetaminophen
induced liver damage in patients.
PMID- 27499849
TI - Recent advances in phototherapy for psoriasis.
AB - Phototherapy involves repeated exposure of the skin to ultraviolet light to treat
various inflammatory skin conditions such as psoriasis. Recent studies have
identified specific immunologic effects of phototherapy that may underlie
phototherapy efficacy. Furthermore, recent advancements have been made in
developing safe and effective targeted phototherapy modalities for difficult-to
treat areas such as scalp psoriasis. Targeted phototherapy in the form of the
excimer laser holds potential for more aggressive, effective treatment and long
lasting remission of psoriasis. Phototherapy is now also used successfully with
biologic agents as combination therapy to treat recalcitrant psoriasis.
Therefore, though one of the oldest therapeutic modalities for psoriasis,
phototherapy remains a mainstay treatment with promise for further advancement.
PMID- 27499851
TI - (13)C glucose labelling studies using 2D NMR are a useful tool for determining ex
vivo whole organ metabolism during hypothermic machine perfusion of kidneys.
AB - BACKGROUND: The aim of this study is to determine the feasibility of using
nuclear magnetic resonance (NMR) tracer studies ((13)C-enriched glucose) to
detect ex vivo de novo metabolism in the perfusion fluid and cortical tissue of
porcine kidneys during hypothermic machine perfusion (HMP). METHODS: Porcine
kidneys (n = 6) were subjected to 24 h of HMP using the Organ Recovery Systems
LifePort Kidney perfusion device. Glucose, uniformly enriched with the stable
isotope (13)C ([U-(13)C] glucose), was incorporated into KPS-1-like perfusion
fluid at a concentration of 10 mM. Analysis of perfusate was performed using both
1D (1)H and 2D (1)H,(13)C heteronuclear single quantum coherence (HSQC) NMR
spectroscopy. The metabolic activity was then studied by quantifying the
proportion of key metabolites containing (13)C in both perfusate and tissue
samples. RESULTS: There was significant enrichment of (13)C in a number of
central metabolites present in both the perfusate and tissue extracts and was
most pronounced for lactate and alanine. The total amount of enriched lactate
(per sample) in perfusion fluid increased during HMP (31.1 +/- 12.2 nmol at 6 h
vs 93.4 +/- 25.6 nmol at 24 h p < 0.01). The total amount of enriched alanine
increased in a similar fashion (1.73 +/- 0.89 nmol at 6 h vs 6.80 +/- 2.56 nmol
at 24 h p < 0.05). In addition, small amounts of enriched acetate and glutamic
acid were evident in some samples. CONCLUSIONS: This study conclusively
demonstrates that de novo metabolism occurs during HMP and highlights active
metabolic pathways in this hypothermic, hypoxic environment. Whilst the majority
of the (13)C-enriched glucose is metabolised into glycolytic endpoint metabolites
such as lactate, the presence of non-glycolytic pathway derivatives suggests that
metabolism during HMP is more complex than previously thought. Isotopic labelled
ex vivo organ perfusion studies using 2D NMR are feasible and informative.
PMID- 27499852
TI - Carriage of multidrug-resistant organisms in a tertiary university hospital in
Albania-a point prevalence survey.
AB - BACKGROUND: Antimicrobial resistance has been recognised as a serious global
Public Health problem. Prevalence of Multiple-Drug-Resistant (MDR) organism
carriage in Albania is largely unknown since no national surveillance system is
in place and few publications are accessible in the literature. METHODS: A 1-day
point-prevalence-survey (PPS) screening for nasal methicillin-resistant
Staphylococcus aureus (MRSA) and rectal MDR Gram-negative carriage was carried
out at the high-dependency wards in the country's only tertiary care hospital, in
Tirana. RESULTS: A total of 106 nasal and 104 rectal swabs were collected. 14.2 %
of patients (95 % Confidence Interval [95 CI]: 8.1-22.3 %) were MRSA nasal
carriers. Resistance to aminoglycosides and fluoroquinolones was common in these
isolates (>=80 %) but no resistance was identified against glycopeptides,
nitrofurantoin and the relatively newer agents, tigecycline and linezolid. Fifty
Enterobacteriaceae isolates were cultivated from 33 of 104 screened patients
(31.7 % [95 CI: 22.9-41.6 % 95 CI]). The prevalence of Extended Spectrum Beta
Lactamase (ESBL) production in Enterobacteriaceae was 41.3 % (95 CI: 31.8-51.4
%). The two more commonly isolated Enterobacteriaceae were E. coli ([n = 28], 24
ESBL positive; 1 AmpC positive and 3 without an identified mechanism of
resistance) and Klebsiella pneumoniae ([n = 13], all ESBL positive; 1 also AmpC
and metallo-beta-lactamase (MBL) positive). Susceptibility to carbapenems (>=98
%), fosfomycin (90 %) and amikacin (70 + 20 % intermediate) was high but a high
level of resistance to all other agents tested was noted. Non-fermenting Gram
negative bacilli were less commonly isolated {22 isolates: Acinetobacter
baumannii (9); Pseudomonas aeruginosa (8) and Stenotrophomonas maltophilia (5)}.
CONCLUSION: Although a significant rate of MRSA carriage was identified, the main
resistance challenge in Albania appears to be linked with Gram-negative
organisms, particularly ESBL in Enterobacteriaceae.
PMID- 27499853
TI - Increased maternal consumption of methionine as its hydroxyl analog promoted
neonatal intestinal growth without compromising maternal energy homeostasis.
AB - BACKGROUND: To determine responses of neonatal intestine to maternal increased
consumption of DL-methionine (DLM) or DL-2-hydroxy-4-methylthiobutanoic acid
(HMTBA), eighteen primiparous sows (Landrace * Yorkshire) were allocated based on
body weight and backfat thickness to the control, DLM and HMTBA groups (n = 6),
with the nutritional treatments introduced from postpartum d0 to d14. RESULTS:
The DLM-fed sows showed negative energy balance manifested by lost bodyweight,
lower plasma glucose, subdued tricarboxylic acid cycle, and increased plasma
lipid metabolites levels. Both villus height and ratio of villus height to crypt
depth averaged across the small intestine of piglets were higher in the DLM and
HMTBA groups than in the control group. Piglet jejunal oxidized glutathione
concentration and ratio of oxidized to reduced glutathione were lower in the
HMTBA group than in the DLM and control groups. However, piglet jejunal
aminopeptidase A, carnitine transporter 2 and IGF-II precursor mRNA abundances
were higher in the DLM group than in the HMTBA and control groups. CONCLUSION:
Increasing maternal consumption of methionine as DLM and HMTBA promoted neonatal
intestinal growth by increasing morphological development or up-regulating
expression of genes responsible for nutrient metabolism. And increasing maternal
consumption of HMTBA promoted neonatal intestinal antioxidant capacity without
compromising maternal energy homeostasis during early lactation.
PMID- 27499854
TI - Mechanical loading inhibits hypertrophy in chondrogenically differentiating hMSCs
within a biomimetic hydrogel.
AB - Three dimensional hydrogels are a promising vehicle for delivery of adult human
bone-marrow derived mesenchymal stem cells (hMSCs) for cartilage tissue
engineering. One of the challenges with using this cell type is the default
pathway is terminal differentiation, a hypertrophic phenotype and precursor to
endochondral ossification. We hypothesized that a synthetic hydrogel consisting
of extracellular matrix (ECM) analogs derived from cartilage when combined with
dynamic loading provides physiochemical cues for achieving a stable chondrogenic
phenotype. Hydrogels were formed from crosslinked poly(ethylyene glycol) as the
base chemistry and to which (meth)acrylate functionalized ECM analogs of RGD
(cell adhesion peptide) and chondroitin sulfate (ChS, a negatively charged
glycosaminoglycan) were introduced. Bone-marrow derived hMSCs from three donors
were encapsulated in the hydrogels and cultured under free swelling conditions or
under dynamic com pressive loading with 2.5 ng/ml TGF-beta3. hMSC differentiation
was assessed by quantitative PCR and immunohistochemistry. Nine hydrogel
formulations were initially screened containing 0, 0.1 or 1mM RGD and 0, 1 or
2wt% ChS. After 21 days, the 1% ChS and 0.1 mM RGD hydrogel had the highest
collagen II gene expression, but this was accompanied by high collagen X gene
expression. At the protein level, collagen II was detected in all formulations
with ECM analogs, but minimally detectable in the hydrogel without ECM analogs.
Collagen X protein was present in all formulations. The 0.1 mM RGD and 1% ChS
formulation was selected and subjected to five loading regimes: no loading, 5%
strain 0.3Hz (1.5%/s), 10% strain 0.3 Hz (3%/s), 5% strain 1 Hz (5%/s), and 10%
strain 1Hz (10%/s). After 21 days, ~70-90% of cells stained positive for collagen
II protein regardless of the culture condition. On the contrary, only ~20-30% of
cells stained positive for collagen X protein under 3 and 5%/s loading
conditions, which was accompanied by minimal staining for RunX2. The other
culture conditions had more cells staining positive for collagen X (40-60%) and
was accompanied by positive staining for RunX2. In summary, a cartilage-like
biomimetic hydrogel supports chondrogenesis of hMSCs, but dynamic loading only
under select strain rates is able to inhibit hypertrophy.
PMID- 27499856
TI - EDITORIAL.
PMID- 27499855
TI - Environmentally induced, occupational diseases with emphasis on chronic kidney
disease of multifactorial origin affecting tropical countries.
AB - BACKGROUND: Environmentally induced, occupational diseases are increasing
worldwide, especially in rural agricultural communities. Poverty-associated
malnutrition, environmental hazards and pollution, and lack of access to clean
water, safe sanitation, and modern healthcare facilities are often associated
with these chronic illnesses. METHOD: The authors systematically reviewed
occupational public health issues that have been related to the environment.
General interpretations of results were included as per the guidelines of the
Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Pertinent
publications from research databases were reviewed on (A) the risk-benefits, (B)
the prevalence of risk factors for various diseases, (C) the benefits of not
ignoring the risk factors (i.e., broader evidence), and (D) the risks, effects,
and outcomes of different types of interventions. The authors used chronic kidney
disease of multifactorial origin (CKDmfo) as an example to explore the theme.
Emphasis was given to the regions with emerging economies and developing
countries located in the vicinity of the equator. FINDINGS: Geographical, socio
economic and aetiological similarities exist for many chronic non-communicable
diseases that are affecting tropical countries around the equator. The authors
identified manufacturing, mining, and agriculture as the biggest polluters of the
environment. In addition, deforestation and associated soil erosion, overuse of
agrochemicals, and irresponsible factory discharge (e.g., chemicals and paint,
from rubber and textile factories, etc.), all contribute to pollution. To
decrease the escalating incidences of environmentally induced diseases,
governments should work proactively to protect the environment, especially
watersheds, and take steps to minimise harmful occupational exposures and
strictly enforce environmental regulations. CONCLUSION: Creating public awareness
of environmental issues and their relationship to public health is essential.
This includes regular monitoring and periodic publication of the quality of
water, air and soil; preventing deforestation and man-made soil erosion,
increasing forest and ground cover, preventing occupational injuries, judicious
and safe use of agrochemicals, sustainable agriculture and development programs,
and implementing legislation to protect and conserve water heriage and the
environment. These actions are essential both for a healthier environment and for
the health of the people who live in that environment. Such measures would also
decrease public health threats from such, including global-warming-related
erratic environmental changes and the occurrence and the spread of non
communicable diseases, such as CKDmfo.
PMID- 27499857
TI - Experimentally induced metamorphosis in axolotls reduces regenerative rate and
fidelity.
AB - While most tetrapods are unable to regenerate severed body parts, amphibians
display a remarkable ability to regenerate an array of structures. Frogs can
regenerate appendages as larva, but they lose this ability around metamorphosis.
In contrast, salamanders regenerate appendages as larva, juveniles, and adults.
However, the extent to which fundamental traits (e.g., metamorphosis, body size,
aging, etc.) restrict regenerative ability remains contentious. Here we utilize
the ability of normally paedomorphic adult axolotls (Ambystoma mexicanum) to
undergo induced metamorphosis by thyroxine exposure to test how metamorphosis and
body size affects regeneration in age-matched paedomorphic and metamorphic
individuals. We show that body size does not affect regeneration in adult
axolotls, but metamorphosis causes a twofold reduction in regeneration rate, and
lead to carpal and digit malformations. Furthermore, we find evidence that
metamorphic blastemal cells may take longer to traverse the cell cycle and
display a lower proliferative rate. This study identifies the axolotl as a
powerful system to study how metamorphosis restricts regeneration independently
of developmental stage, body size, and age; and more broadly how metamorphosis
affects tissue-specific changes.
PMID- 27499858
TI - Position-specific induction of ectopic limbs in non-regenerating blastemas on
axolotl forelimbs.
AB - Ectopic retinoic acid (RA) has been hypothesized to reprogram the positional
identity of cells in developing and regenerating limbs to a single positional
value corresponding to the posterior-ventral-proximal (PVPr) position on the
limb. We tested this hypothesis by using RA to reprogram the information of
blastema cells that were induced to form at different positions around the limb
circumference. We observed that RA treatment of blastemas in anterior and dorsal
locations, but not posterior and ventral locations, resulted in the induction of
complete ectopic limbs. These position-specific differences in limb induction are
probably due to differences in the positional disparity between the RA
reprogrammed blastema cells and the cells at the periphery of the wound. These
observations are consistent with the hypothesis that RA treatment reprograms the
information in blastema cells to the PVPr position on the limb, since anterior
and dorsal positions have the largest disparity and posterior and ventral have
the smallest disparity from the PVPr identity.
PMID- 27499859
TI - Ectopic blastema induction by nerve deviation and skin wounding: a new
regeneration model in Xenopus laevis.
AB - Recently, the accessory limb model (ALM) has become an alternative study system
for limb regeneration studies in axolotls instead of using an amputated limb. ALM
progresses limb regeneration study in axolotls because of its advantages. To
apply and/or to compare knowledge in axolotl ALM studies to other vertebrates is
a conceivable next step. First, Xenopus laevis, an anuran amphibian, was
investigated. A Xenopus frog has hypomorphic regeneration ability. Its
regeneration ability has been considered intermediate between that of non
regenerative higher vertebrates and regenerative urodele amphibians. Here, we
successfully induced an accessory blastema in Xenopus by skin wounding and
rerouting of brachial nerve bundles to the wound site, which is the regular ALM
surgery. The induced Xenopus ALM blastemas have limited regenerative potential
compared with axolotl ALM blastemas. Comparison of ALM blastemas from species
with different regenerative potentials may facilitate the identification of the
novel expression programs necessary for the formation of cartilage and other
tissues during limb regeneration.
PMID- 27499860
TI - Implication of two different regeneration systems in limb regeneration.
AB - Limb regeneration is a representative phenomenon of organ regeneration in urodele
amphibians, such as an axolotl. An amputated limb starts regenerating from a
remaining stump (proximal) to lost finger tips (distal). In the present case,
proximal-distal (PD) reorganization takes place in a regenerating tissue, called
a blastema. It has been a mystery how an induced blastema recognizes its position
and restores an exact replica of missing parts. Recently, a new experimental
system called the accessory limb model (ALM) has been established. The gained ALM
phenotypes are demanding to reconsider the reorganization PD positional values.
Based on the ALM phenotype, it is reasonable to hypothesize that reorganization
of positional values has a certain discontinuity and that two different
regeneration systems cooperatively reorganize the PD axis to restore an original
structure. In this review, PD axis reestablishments are focused on limb
regeneration. Knowledge from ALM studies in axolotls and Xenopus is providing a
novel concept of PD axis reorganization in limb regeneration.
PMID- 27499861
TI - Temporal and spatial analysis of enteric nervous system regeneration in the sea
cucumber Holothuria glaberrima.
AB - There is limited information on the regeneration of the enteric nervous system
(ENS) following major reconstruction of the digestive tract. We have studied ENS
regeneration in the sea cucumber Holothuria glaberrima which undergoes an
organogenic process forming a new digestive tract at the tip of the mesentery.
Our results show that (1) a degeneration of nerve fibers occurs early in the
regeneration process, prior to eventual regeneration; (2) nerve fibers that
innervate the regenerating intestine are of extrinsic and intrinsic origin; (3)
innervation by extrinsic fibers occurs in a gradient that begins in the proximal
area of the regenerate; (4) late events include the appearance of nerve fibers
that project from the serosa into the connective tissue and of nerve bundles in
the mesothelial layer; (5) neurons and neuroendocrine cells appear early
following the formation of the epithelial layers. Our results provide not only a
comparative biological approach to study ENS regeneration but also an alternative
point of view for the study of enteric neuropathologies and for the innervation
of organs made in vitro.
PMID- 27499863
TI - Plasticity for axolotl lens regeneration is associated with age-related changes
in gene expression.
AB - Mexican axolotls lose potential for lens regeneration 2 weeks after hatching. We
used microarrays to identify differently expressed genes before and after this
critical time, using RNA isolated from iris. Over 3700 genes were identified as
differentially expressed in response to lentectomy between young (7 days post
hatching) and old (3 months post-hatching) axolotl larvae. Strikingly, many of
the genes were only expressed in the early or late iris. Genes that were highly
expressed in young iris significantly enriched electron transport chain,
transcription, metabolism, and cell cycle gene ontologies, all of which are
associated with lens regeneration. In contrast, genes associated with cellular
differentiation and tissue maturation were uniquely expressed in old iris. Many
of these expression differences strongly suggest that young and old iris samples
were collected before and after the spleen became developmentally competent to
produce and secrete cells with humoral and innate immunity functions. Our study
establishes the axolotl as a powerful model to investigate age-related cellular
differentiation and immune system ontogeny within the context of tissue
regeneration.
PMID- 27499862
TI - Angiogenesis is inhibitory for mammalian digit regeneration.
AB - The regenerating mouse digit tip is a unique model for investigating blastema
formation and epimorphic regeneration in mammals. The blastema is
characteristically avascular and we previously reported that blastema expression
of a known anti-angiogenic factor gene, Pedf, correlated with a successful
regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka,
K. (2010). BMP signaling induces digit regeneration in neonatal mice.
Development, 137, 551-559). Here we show that during regeneration Vegfa
transcripts are not detected in the blastema but are expressed at the onset of
differentiation. Treating the amputation wound with vascular endothelial growth
factor enhances angiogenesis but inhibits regeneration. We next tested bone
morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found
that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces
Vegfa expression in the digit stump suggesting that regenerative failure is
mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of
regeneration is completely rescued by treatment with pigment epithelium-derived
factor. These studies show that precocious angiogenesis is inhibitory for
regeneration, and provide compelling evidence that the regulation of angiogenesis
is a critical factor in designing therapies aimed at stimulating mammalian
regeneration.
PMID- 27499864
TI - Distinct patterns of endosulfatase gene expression during Xenopus laevis limb
development and regeneration.
AB - The heparan sulfate 6-O-endosulfatases sulf1 and sulf2 regulate multiple cellular
processes and organ development. Sulfs modulate a range of heparan-sulfate
dependent extracellular pathways, including the fibroblast growth factor, bone
morphogenetic protein, and wingless/wnt signaling pathways. Known patterns of
sulf transcript expression together with functional experiments have implicated
the sulfs in chondrogenesis and muscle regeneration in mammals. Here, we describe
the expression patterns of Xenopus laevis sulf1 and sulf2 in developing forelimbs
and hindlimbs and demonstrate novel expression of the sulf transcripts in the
regenerating hindlimbs, with prominent sulf2 expression in the proliferating
blastema and transient expression of sulf1 in the redeveloping apical epidermal
ridge. These findings further suggest involvement of the sulfs in successful limb
regeneration in amphibians.
PMID- 27499866
TI - TALEN-mediated gene editing of the thrombospondin-1 locus in axolotl.
AB - Loss-of-function genetics provides strong evidence for a gene's function in a
wild-type context. In many model systems, this approach has been invaluable for
discovering the function of genes in diverse biological processes. Axolotls are
urodele amphibians (salamanders) with astonishing regenerative abilities, capable
of regenerating entire limbs, portions of the tail (including spinal cord),
heart, and brain into adulthood. With their relatively short generation time
among salamanders, they offer an outstanding opportunity to interrogate natural
mechanisms for appendage and organ regeneration provided that the tools are
developed to address these long-standing questions. Here we demonstrate targeted
modification of the thrombospondin-1 (tsp-1) locus using transcription-activator
like effector nucleases (TALENs) and identify a role of tsp-1 in recruitment of
myeloid cells during limb regeneration. We find that while tsp-1-edited mosaic
animals still regenerate limbs, they exhibit a reduced subepidermal collagen
layer in limbs and an increased number of myeloid cells within blastemas. This
work presents a protocol for generating and genotyping mosaic axolotls with TALEN
mediated gene edits.
PMID- 27499865
TI - Reintegration of the regenerated and the remaining tissues during joint
regeneration in the newt Cynops pyrrhogaster.
AB - Urodele amphibians, such as newts, can regenerate a functional limb, including
joints, after amputation at any level along the proximal-distal axis of the limb.
The blastema can regenerate the limb morphology largely independently of the
stump after proximal-distal identity has been established, but the remaining and
regenerated tissues must be structurally reintegrated (matched in size and
shape). Here we used newt joint regeneration as a model to investigate
reintegration, because a functionally interlocking joint requires structural
integration between its opposing skeletal elements. After forelimbs were
amputated at the elbow joint, the joint was regenerated between the remaining and
regenerated skeletal elements. The regenerated cartilage was thick around the
amputated joint to make a reciprocally interlocking joint structure with the
remaining bone. Furthermore, during regeneration, the extracellular matrix of the
remaining tissues was lost, suggesting that the remaining tissues might
contribute to the morphogenesis of regenerating cartilage. Our results showed
that the area of the regenerated cartilage matched the area of the apposed
remaining cartilage, thus contributing to formation of a functional structure.
PMID- 27499867
TI - The regeneration blastema of lizards: an amniote model for the study of appendage
replacement.
AB - Although amniotes (reptiles, including birds, and mammals) are capable of
replacing certain tissues, complete appendage regeneration is rare. Perhaps the
most striking example is the lizard tail. Tail loss initiates a spontaneous
epimorphic (blastema-mediated) regenerative program, resulting in a fully
functional but structurally non-identical replacement. Here we review lizard tail
regeneration with a particular focus on the blastema. In many lizards, the
original tail has evolved a series of fracture planes, anatomical modifications
that permit the tail to be self-detached or autotomized. Following tail loss, the
wound site is covered by a specialized wound epithelium under which the blastema
develops. An outgrowth of the spinal cord, the ependymal tube, plays a key role
in governing growth (and likely patterning) of the regenerate tail. In some
species (e.g., geckos), the blastema forms as an apical aggregation of
proliferating cells, similar to that of urodeles and teleosts. For other species
(e.g., anoles) the identification of a proliferative blastema is less obvious,
suggesting an unexpected diversity in regenerative mechanisms among tail
regenerating lizards.
PMID- 27499868
TI - The axolotl limb blastema: cellular and molecular mechanisms driving blastema
formation and limb regeneration in tetrapods.
AB - The axolotl is one of the few tetrapods that are capable of regenerating
complicated biological structures, such as complete limbs, throughout adulthood.
Upon injury the axolotl generates a population of regeneration-competent limb
progenitor cells known as the blastema, which will grow, establish pattern, and
differentiate into the missing limb structures. In this review we focus on the
crucial early events that occur during wound healing, the neural-epithelial
interactions that drive the formation of the early blastema, and how these
mechanisms differ from those of other species that have restricted regenerative
potential, such as humans. We also discuss how the presence of cells from the
different axes of the limb is required for the continued growth and establishment
of pattern in the blastema as described in the polar coordinate model, and how
this positional information is reprogrammed in blastema cells during
regeneration. Multiple cell types from the mature limb stump contribute to the
blastema at different stages of regeneration, and we discuss the contribution of
these types to the regenerate with reference to whether they are "pattern
forming" or "pattern-following" cells. Lastly, we explain how an engineering
approach will help resolve unanswered questions in limb regeneration, with the
goal of translating these concepts to developing better human regenerative
therapies.
PMID- 27499869
TI - The art of fin regeneration in zebrafish.
AB - The zebrafish fin provides a valuable model to study the epimorphic type of
regeneration, whereby the amputated part of the appendage is nearly perfectly
replaced. To accomplish fin regeneration, two reciprocally interacting domains
need to be established at the injury site, namely a wound epithelium and a
blastema. The wound epithelium provides a supporting niche for the blastema,
which contains mesenchyme-derived progenitor cells for the regenerate. The fate
of blastemal daughter cells depends on their relative position with respect to
the fin margin. The apical compartment of the outgrowth maintains its
undifferentiated character, whereas the proximal descendants of the blastema
progressively switch from the proliferation program to the morphogenesis program.
A delicate balance between self-renewal and differentiation has to be
continuously adjusted during the course of regeneration. This review summarizes
the current knowledge about the cellular and molecular mechanisms of blastema
formation, and discusses several studies related to the regulation of growth and
morphogenesis during fin regeneration. A wide range of canonical signaling
pathways has been implicated during the establishment and maintenance of the
blastema. Epigenetic mechanisms play a crucial role in the regulation of cellular
plasticity during the transition between differentiation states. Ion fluxes, gap
junctional communication and protein phosphatase activity have been shown to
coordinate proliferation and tissue patterning in the caudal fin. The
identification of the downstream targets of the fin regeneration signals and the
discovery of mechanisms integrating the variety of input pathways represent
exciting future aims in this fascinating field of research.
PMID- 27499870
TI - Current advances in tissue repair and regeneration: the future is bright.
AB - The fifth EMBO conference on 'The Molecular and Cellular Basis of Regeneration
and Repair' took place in the peaceful coastal town of Sant Feliu de Guixols
(Spain) on September 2014. The meeting was organised by Emili Salo (U. Barcelona,
Spain), Kimberly Mace (U. Manchester, UK), Patrizia Ferretti (University College
London, UK) and Michael Brand (Centre for Regenerative Therapies Dresden,
Germany) and received the generous support of Society for Developmental Biology,
The Company of Biologists, Centre for Regenerative Therapies Dresden, Garland
Science and the journals Regeneration and Cell Signalling. The natural
surroundings provided an inspiring setting for 185 researchers from all over the
world to share their latest findings and views on the field. The conference
showcased the great diversity of model organisms used for studying regeneration
and tissue repair, including invertebrate and vertebrate species (Fig. 1).
Importantly, this diversity in animal models allowed for a global overview of the
mechanisms that promote regeneration. In addition, it highlighted some of the
unique aspects that confer differences in regenerative capacities among different
species. These differences might lie in each of the different steps involved in
performing regeneration, including triggering the regenerative response,
controlling cellular plasticity, re-stablishing the correct tissue patterns, as
well as determining the roles of extrinsic factors, such as the role of
inflammation in regeneration. A deeper understanding of these processes in the
naturally regenerating species is a prerequisite for advancing the field of
regenerative medicine and tissue repair in humans.
PMID- 27499871
TI - The mammalian blastema: regeneration at our fingertips.
AB - In the mouse, digit tip regeneration progresses through a series of discrete
stages that include inflammation, histolysis, epidermal closure, blastema
formation, and redifferentiation. Recent studies reveal how each regenerative
stage influences subsequent stages to establish a blastema that directs the
successful regeneration of a complex mammalian structure. The focus of this
review is on early events of healing and how an amputation wound transitions into
a functional blastema. The stepwise formation of a mammalian blastema is proposed
to provide a model for how specific targeted treatments can enhance regenerative
performance in humans.
PMID- 27499872
TI - Epidermal closure regulates histolysis during mammalian (Mus) digit regeneration.
AB - Mammalian digit regeneration progresses through consistent stages: histolysis,
inflammation, epidermal closure, blastema formation, and finally
redifferentiation. What we do not yet know is how each stage can affect others.
Questions of stage timing, tissue interactions, and microenvironmental states are
becoming increasingly important as we look toward solutions for whole limb
regeneration. This study focuses on the timing of epidermal closure which, in
mammals, is delayed compared to more regenerative animals like the axolotl. We
use a standard wound closure device, Dermabond (2-octyl cyanoacrylate), to induce
earlier epidermal closure, and we evaluate the effect of fast epidermal closure
on histolysis, blastema formation, and redifferentiation. We find that fast
epidermal closure is reliant upon a hypoxic microenvironment. Additionally, early
epidermal closure eliminates the histolysis stage and results in a regenerate
that more closely replicates the amputated structure. We show that tools like
Dermabond and oxygen are able to independently influence the various stages of
regeneration enabling us to uncouple histolysis, wound closure, and other
regenerative events. With this study, we start to understand how each stage of
mammalian digit regeneration is controlled.
PMID- 27499873
TI - Regeneration and repair of human digits and limbs: fact and fiction.
AB - A variety of digit and limb repair and reconstruction methods have been used in
different clinical settings, but regeneration remains an item on every plastic
surgeon's "wish list." Although surgical salvage techniques are continually being
improved, unreplantable digits and limbs are still abundant. We comprehensively
review the structural and functional salvage methods in clinical practice, from
the peeling injuries of small distal fingertips to multisegmented amputated
limbs, and the developmental and tissue engineering approaches for regenerating
human digits and limbs in the laboratory. Although surgical techniques have
forged ahead, there are still situations in which digits and limbs are
unreplantable. Advances in the field are delineated, and the regeneration
processes of salamander limbs, lizard tails, and mouse digits and each component
of tissue engineering approaches for digit- and limb-building are discussed.
Although the current technology is promising, there are many challenges in human
digit and limb regeneration. We hope this review inspires research on the
critical gap between clinical and basic science, and leads to more sophisticated
digit and limb loss rescue and regeneration innovations.
PMID- 27499874
TI - Positional information in axolotl and mouse limb extracellular matrix is mediated
via heparan sulfate and fibroblast growth factor during limb regeneration in the
axolotl (Ambystoma mexicanum).
AB - Urodele amphibians are unique among adult vertebrates in their ability to
regenerate complex body structures after traumatic injury. In salamander
regeneration, the cells maintain a memory of their original position and use this
positional information to recreate the missing pattern. We used an in vivo gain
of-function assay to determine whether components of the extracellular matrix
(ECM) have positional information required to induce formation of new limb
pattern during regeneration. We discovered that salamander limb ECM has a
position-specific ability to either inhibit regeneration or induce de novo limb
structure, and that this difference is dependent on heparan sulfates that are
associated with differential expression of heparan sulfate sulfotransferases. We
also discovered that an artificial ECM containing only heparan sulfate was
sufficient to induce de novo limb pattern in salamander limb regeneration.
Finally, ECM from mouse limbs is capable of inducing limb pattern in axolotl
blastemas in a position-specific, developmental-stage-specific, and heparan
sulfate-dependent manner. This study demonstrates a mechanism for positional
information in regeneration and establishes a crucial functional link between
salamander regeneration and mammals.
PMID- 27499875
TI - Skeletal callus formation is a nerve-independent regenerative response to limb
amputation in mice and Xenopus.
AB - To clarify the mechanism of limb regeneration that differs between mammals (non
regenerative) and amphibians (regenerative), responses to limb amputation and the
accessory limb inducible surgery (accessory limb model, ALM) were compared
between mice and Xenopus, focusing on the events leading to blastema formation.
In both animals, cartilaginous calluses were formed around the cut edge of bones
after limb amputation. They not only are morphologically similar but show other
similarities, such as growth driven by undifferentiated cell proliferation and
macrophage-dependent and nerve-independent induction. It appears that amputation
callus formation is a common nerve-independent regenerative response in mice and
Xenopus. In contrast, the ALM revealed that the wound epithelium (WE) in Xenopus
was innervated by many regenerating axons when a severed nerve ending was placed
underneath it, whereas only a few axons were found within the WE in mice. Since
nerves are involved in induction of the regeneration-permissive WE in amphibians,
whether or not nerves can interact with the WE might be one of the key processes
separating successful nerve-dependent blastema formation in Xenopus and failure
in mice.
PMID- 27499877
TI - Functional joint regeneration is achieved using reintegration mechanism in
Xenopus laevis.
AB - A functional joint requires integration of multiple tissues: the apposing
skeletal elements should form an interlocking structure, and muscles should
insert into skeletal tissues via tendons across the joint. Whereas newts can
regenerate functional joints after amputation, Xenopus laevis regenerates a
cartilaginous rod without joints, a "spike." Previously we reported that the
reintegration mechanism between the remaining and regenerated tissues has a
significant effect on regenerating joint morphogenesis during elbow joint
regeneration in newt. Based on this insight into the importance of reintegration,
we amputated frogs' limbs at the elbow joint and found that frogs could
regenerate a functional elbow joint between the remaining tissues and regenerated
spike. During regeneration, the regenerating cartilage was partially connected to
the remaining articular cartilage to reform the interlocking structure of the
elbow joint at the proximal end of the spike. Furthermore, the muscles of the
remaining part inserted into the regenerated spike cartilage via tendons. This
study might open up an avenue for analyzing molecular and cellular mechanisms of
joint regeneration using Xenopus.
PMID- 27499876
TI - Genome-wide analysis reveals conserved transcriptional responses downstream of
resting potential change in Xenopus embryos, axolotl regeneration, and human
mesenchymal cell differentiation.
AB - Endogenous bioelectric signaling via changes in cellular resting potential (V
mem) is a key regulator of patterning during regeneration and embryogenesis in
numerous model systems. Depolarization of V mem has been functionally implicated
in dedifferentiation, tumorigenesis, anatomical re-specification, and appendage
regeneration. However, no unbiased analyses have been performed to understand
genome-wide transcriptional responses to V mem change in vivo. Moreover, it is
unknown which genes or gene networks represent conserved targets of bioelectrical
signaling across different patterning contexts and species. Here, we use
microarray analysis to comparatively analyze transcriptional responses to V mem
depolarization. We compare the response of the transcriptome during embryogenesis
(Xenopus development), regeneration (axolotl regeneration), and stem cell
differentiation (human mesenchymal stem cells in culture) to identify common
networks across model species that are associated with depolarization. Both
subnetwork enrichment and PANTHER analyses identified a number of key genetic
modules as targets of V mem change, and also revealed important (well-conserved)
commonalities in bioelectric signal transduction, despite highly diverse
experimental contexts and species. Depolarization regulates specific
transcriptional networks across all three germ layers (ectoderm, mesoderm, and
endoderm) such as cell differentiation and apoptosis, and this information will
be used for developing mechanistic models of bioelectric regulation of
patterning. Moreover, our analysis reveals that V mem change regulates
transcripts related to important disease pathways such as cancer and
neurodegeneration, which may represent novel targets for emerging electroceutical
therapies.
PMID- 27499878
TI - Analogous cellular contribution and healing mechanisms following digit amputation
and phalangeal fracture in mice.
AB - Regeneration of amputated structures is severely limited in humans and mice, with
complete regeneration restricted to the distal portion of the terminal phalanx
(P3). Here, we investigate the dynamic tissue repair response of the second
phalangeal element (P2) post amputation in the adult mouse, and show that the
repair response of the amputated bone is similar to the proximal P2 bone fragment
in fracture healing. The regeneration-incompetent P2 amputation response is
characterized by periosteal endochondral ossification resulting in the deposition
of new trabecular bone, corresponding to a significant increase in bone volume;
however, this response is not associated with bone lengthening. We show that
cells of the periosteum respond to amputation and fracture by contributing both
chondrocytes and osteoblasts to the endochondral ossification response. Based on
our studies, we suggest that the amputation response represents an attempt at
regeneration that ultimately fails due to the lack of a distal organizing
influence that is present in fracture healing.
PMID- 27499879
TI - Ear wound regeneration in the African spiny mouse Acomys cahirinus.
AB - While regeneration occurs in a number of taxonomic groups across the Metazoa,
there are very few reports of regeneration in mammals, which generally respond to
wounding with fibrotic scarring rather than regeneration. A recent report
described skin shedding, skin regeneration and extensive ear punch closure in two
rodent species, Acomys kempi and Acomys percivali. We examined these striking
results by testing the capacity for regeneration of a third species, Acomys
cahirinus, and found a remarkable capacity to repair full thickness circular
punches in the ear pinna. Four-millimeter-diameter wounds closed completely in 2
months in 100% of ear punches tested. Histology showed extensive formation of
elastic cartilage, adipose tissue, dermis, epidermis and abundant hair follicles
in the repaired region. Furthermore, we demonstrated abundant angiogenesis and
unequivocal presence of both muscle and nerve fibers in the reconstituted region;
in contrast, similar wounds in C57BL/6 mice simply healed the borders of the cut
by fibrotic scarring. Our results confirm the regenerative capabilities of
Acomys, and suggest this model merits further attention.
PMID- 27499880
TI - Planarian brain regeneration as a model system for developmental neurotoxicology.
AB - Freshwater planarians, famous for their regenerative prowess, have long been
recognized as a valuable in vivo animal model to study the effects of chemical
exposure. In this review, we summarize the current techniques and tools used in
the literature to assess toxicity in the planarian system. We focus on the
planarian's particular amenability for neurotoxicology and neuroregeneration
studies, owing to the planarian's unique ability to regenerate a centralized
nervous system. Zooming in from the organismal to the molecular level, we show
that planarians offer a repertoire of morphological and behavioral readouts while
also being amenable to mechanistic studies of compound toxicity. Finally, we
discuss the open challenges and opportunities for planarian brain regeneration to
become an important model system for modern toxicology.
PMID- 27499882
TI - The relationship between growth and pattern formation.
AB - Successful development depends on the creation of spatial gradients of
transcription factors within developing fields, and images of graded
distributions of gene products populate the pages of developmental biology
journals. Therefore the challenge is to understand how the graded levels of
intracellular transcription factors are generated across fields of cells. We
propose that transcription factor gradients are generated as a result of an
underlying gradient of cell cycle lengths. Very long cell cycles will permit
accumulation of a high level of a gene product encoded by a large transcription
unit, whereas shorter cell cycles will permit progressively fewer transcripts to
be completed due to gating of transcription by the cell cycle. We also propose
that the gradients of cell cycle lengths are generated by gradients of
extracellular morphogens/growth factors. The model of cell cycle gated
transcriptional regulation brings focus back to the functional role of morphogens
as cell cycle regulators, and proposes a specific and testable mechanism by which
morphogens, in their roles as growth factors (how they were originally
discovered), also determine cell fate.
PMID- 27499883
TI - Pilot study of a compassion meditation intervention in chronic pain.
AB - BACKGROUND: The emergence of anger as an important predictor of chronic pain
outcomes suggests that treatments that target anger may be particularly useful
within the context of chronic pain. Eastern traditions prescribe compassion
cultivation to treat persistent anger. Compassion cultivation has been shown to
influence emotional processing and reduce negativity bias in the contexts of
emotional and physical discomfort, thus suggesting it may be beneficial as a dual
treatment for pain and anger. Our objective was to conduct a pilot study of a 9
week group compassion cultivation intervention in chronic pain to examine its
effect on pain severity, anger, pain acceptance and pain-related interference. We
also aimed to describe observer ratings provided by patients' significant others
and secondary effects of the intervention. METHODS: Pilot clinical trial with
repeated measures design that included a within-subjects wait-list control
period. Twelve chronic pain patients completed the intervention (F= 10). Data
were collected from patients at enrollment, treatment baseline and post
treatment; participant significant others contributed data at the enrollment and
post-treatment time points. RESULTS: In this predominantly female sample,
patients had significantly reduced pain severity and anger and increased pain
acceptance at post-treatment compared to treatment baseline. Significant other
qualitative data corroborated patient reports for reductions in pain severity and
anger. CONCLUSIONS: Compassion meditation may be a useful adjunctive treatment
for reducing pain severity and anger, and for increasing chronic pain acceptance.
Patient reported reductions in anger were corroborated by their significant
others. The significant other corroborations offer a novel contribution to the
literature and highlight the observable emotional and behavioral changes in the
patient participants that occurred following the compassion intervention. Future
studies may further examine how anger reductions impact relationships with self
and others within the context of chronic pain.
PMID- 27499884
TI - Concordance of In-Home "Smart" Scale Measurement with Body Weight Measured In
Person.
AB - OBJECTIVE: Newer "smart" scales that transmit participants' body weights directly
to data collection centers offer the opportunity to simplify weight assessment in
weight management research; however, little data exist on the concordance of
these data compared to weights measured at in-person assessments. METHODS: We
compared the weights of 58 participants (mean+/-SD BMI = 31.6+/-4.8, age = 52.1+/
9.7 years, 86.2% White, 65.5% Female) measured by study staff at an in-person
assessment visit to weights measured on the same day at home using BodyTrace
"smart" scales. These measures occurred after 3 months of an internet-based
weight management intervention. RESULTS: Weight (mean+/-SD) measured at the 3
month in-person assessment visit was 81.5+/-14.7kg compared to 80.4+/-14.5kg
measured on the same day using in-home body weight scales; mean bias =1.1+/
0.8kg, 95% limits of agreement = -0.5 to 2.6. Two outliers in the data suggest
that there may be greater variability between measurements for participants
weighing above 110 kg. CONCLUSION: Results suggest good concordance between the
measurements and support the use of the BodyTrace smart scale in weight
management research. Future trials using BodyTrace scales for outcome assessment
should clearly define protocols for measurement and associated instructions to
participants (e.g., instruct individuals to weigh at the same time of day,
similarly clothed). Finally, measure concordance should be investigated in a
group of individuals weighing more than 110kg.
PMID- 27499885
TI - Relationship of Physical Activity and Healthy Eating with Mortality and Incident
Heart Failure among Community-Dwelling Older Adults with Normal Body Mass Index.
AB - AIMS: Normal body mass index (BMI) is associated with lower mortality and may be
achieved by physical activity (PA), healthy eating (HE), or both. We examined the
association of PA and HE with mortality and incident heart failure (HF) among
2040 community-dwelling older adults aged >= 65 years with baseline BMI 18.5 to
24.99 kg/m2 during 13 years of follow-up in Cardiovascular Health Study. METHODS
AND RESULTS: Baseline PA was defined as >=500 weekly metabolic equivalent task
minutes (MET-minutes) and HE as >=5 daily servings of vegetable and fruit intake.
Participants were categorized into 4 groups: (1) PA-/HE- (n=384); (2) PA+/HE-
(n=992); (3) PA-/HE+ (n=162); and (4) PA+/HE+ (n=502). Participants had a mean
age of 74 (+/-6) years, mean BMI of 22.6 (+/-1.5) kg/m2, 61% were women, and 4%
African American. Compared with PA-/HE-, age-sex-race-adjusted hazard ratios
(HRs) and 95% confidence intervals (CIs) for all-cause mortality for PA-/HE+,
PA+/HE-, and PA+/HE+ groups were 0.96 (0.76-1.21), 0.61 (0.52-0.71) and 0.62
(0.52-0.75), respectively. These associations remained unchanged after
multivariable adjustment and were similar for cardiovascular and non
cardiovascular mortalities. Respective demographic-adjusted HRs (95% Cis) for
incident HF among 1954 participants without baseline HF were 1.21 (0.81-1.81),
0.71 (0.54-0.94) and 0.71 (0.51-0.98). These later associations lost significance
after multivariable-adjustment. CONCLUSION: Among community-dwelling older adults
with normal BMI, physical activity, regardless of healthy eating, was associated
with lower risk of mortality and incident HF, but healthy eating had no similar
protective association in this cohort.
PMID- 27499881
TI - Physiological controls of large-scale patterning in planarian regeneration: a
molecular and computational perspective on growth and form.
AB - Planaria are complex metazoans that repair damage to their bodies and cease
remodeling when a correct anatomy has been achieved. This model system offers a
unique opportunity to understand how large-scale anatomical homeostasis emerges
from the activities of individual cells. Much progress has been made on the
molecular genetics of stem cell activity in planaria. However, recent data also
indicate that the global pattern is regulated by physiological circuits composed
of ionic and neurotransmitter signaling. Here, we overview the multi-scale
problem of understanding pattern regulation in planaria, with specific focus on
bioelectric signaling via ion channels and gap junctions (electrical synapses),
and computational efforts to extract explanatory models from functional and
molecular data on regeneration. We present a perspective that interprets results
in this fascinating field using concepts from dynamical systems theory and
computational neuroscience. Serving as a tractable nexus between genetic,
physiological, and computational approaches to pattern regulation, planarian
pattern homeostasis harbors many deep insights for regenerative medicine,
evolutionary biology, and engineering.
PMID- 27499886
TI - Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely
ameliorate the progression of chronic kidney diseases.
AB - BACKGROUND: Bio-products from stem/progenitor cells, such as extracellular
vesicles, are likely a new promising approach for reprogramming resident cells in
both acute and chronic kidney disease. Forty CKD patients stage III and IV (eGFR
15-60 mg/ml) have been divided into two groups; twenty patients as treatment
group "A" and twenty patients as a matching placebo group "B". Two doses of MSC
derived extracellular vesicles had been administered to patients of group "A".
Blood urea, serum creatinine, urinary albumin creatinine ratio (UACR) and
estimated glomerular filtration rate (eGFR) have been used to assess kidney
functions and TNF-alpha, TGF-beta1 and IL-10 have been used to assess the
amelioration of the inflammatory immune activity. RESULTS: Participants in group
A exhibited significant improvement of eGFR, serum creatinine level, blood urea
and UACR. Patients of the treatment group "A" also exhibited significant increase
in plasma levels of TGF-beta1, and IL-10 and significant decrease in plasma
levels of TNF-alpha. Participants of the control group B did not show significant
improvement in any of the previously mentioned parameters at any time point of
the study period. CONCLUSION: Administration of cell-free cord-blood mesenchymal
stem cells derived extracellular vesicles (CF-CB-MSCs-EVs) is safe and can
ameliorate the inflammatory immune reaction and improve the overall kidney
function in grade III-IV CKD patients.
PMID- 27499888
TI - The Journal of Pathology: Clinical Research. A new step in the evolution of
publishing in pathology.
PMID- 27499887
TI - Superior absorption and retention properties of foam-film silver dressing versus
other commercially available silver dressing.
AB - BACKGROUND: The aim of this study is to investigate the physicochemical and
structural properties of Medifoam(r)Silver and to compare with other commercially
available silver-containing polyurethane (PU) foam dressing in vitro. METHODS:
Surface and cross-section of four polyurethane foam dressings were assessed with
field-emission scanning electron microscope. Thickness, density, tensile
strength, elongation, absorption rate, absorption/retention capacity and water
vapor transmission (WVT) were measured to compare physical properties of various
dressing materials. RESULTS: Among four tested dressings, Medifoam(r)Silver has
relatively uniform and smallest pore size in both surface and cross-section. In
comparison of absorption properties with other dressing materials,
Medifoam(r)Silver has rapid absorption rate, good absorption/retention capacity
and good WVT value. CONCLUSIONS: The data further suggests that Medifoam(r)Silver
is a promising candidate for wound healing management.
PMID- 27499891
TI - Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation
carriers.
AB - Overexpression of the Aurora A kinase has been shown to have prognostic value in
breast cancer. Previously, we showed a significant association between AURKA gene
amplification and BRCA2 mutation in breast cancer. The aim of this study was to
assess the prognostic impact of Aurora A overexpression on breast cancer arising
in BRCA2 mutation carriers. Aurora A expression was evaluated by
immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5
mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A
nuclear staining was estimated in relation to clinical markers and adjuvant
treatment, using multivariate Cox's proportional hazards ratio regression model.
BRCA2 wild-type allele loss was measured by TaqMan in BRCA2 mutated tumour
samples. All statistical tests were two sided. Multivariate analysis of breast
cancer-specific survival, including proliferative markers and treatment,
indicated independent prognostic value of Aurora A nuclear staining for BRCA2
mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23-40.6; p =
0.028). Poor breast cancer-specific survival of BRCA2 mutation carriers was found
to be significantly associated with combined Aurora A nuclear expression and
BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis
indicated independent prognostic value of both positive Aurora A nuclear staining
(hazards ratio = 10.09; 95% confidence interval = 1.19-85.4, p = 0.034) and BRCA2
wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81-51.0,
p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to
be a significant prognostic marker for BRCA2 mutation carriers, independent of
clinical parameters and adjuvant treatment. Our conclusion is that treatment
benefits for BRCA2 mutation carriers and sporadic breast cancer patients with
Aurora A positive tumours may be enhanced by giving attention to Aurora A
targeted treatment.
PMID- 27499889
TI - The molecular background of mucinous carcinoma beyond MUC2.
AB - The increasing interest of the oncology community in tumour classification and
prediction of outcome to targeted therapies has put emphasis on an improved
identification of tumour types. Colorectal mucinous adenocarcinoma (MC) is a
subtype that is characterized by the presence of abundant extracellular mucin
that comprises at least 50% of the tumour volume and is found in 10-15% of
colorectal cancer patients. MC development is poorly understood, however, the
distinct clinical and pathological presentation of MC suggests a deviant
development and molecular background. In this review we identify common molecular
and genetic alterations in colorectal MC. MC is characterized by a high rate of
MUC2 expression. Mutation rates in the therapeutically important RAS/RAF/MAPK and
PI3K/AKT pathways are significantly higher in MC compared with non-mucinous
adenocarcinoma. Furthermore, mucinous adenocarcinoma shows higher rates of
microsatellite instability and is more frequently of the CpG island methylator
phenotype. Although the majority of MCs arise from the large intestine, this
subtype also develops in other organs, such as the stomach, pancreas, biliary
tract, ovary, breast and lung. We compared findings from colorectal MC with
tumour characteristics of MCs from other organs. In these organs, MCs show
different mutation rates in the RAS/RAF/MAPK and PI3K/AKT pathways as well, but a
common mucinous pathway cannot be identified. Identification of conditions and
molecular aberrations that are associated with MC generates insight into the
aetiology of this subtype and improves understanding of resistance to therapies.
PMID- 27499890
TI - Performance of automated scoring of ER, PR, HER2, CK5/6 and EGFR in breast cancer
tissue microarrays in the Breast Cancer Association Consortium.
AB - Breast cancer risk factors and clinical outcomes vary by tumour marker
expression. However, individual studies often lack the power required to assess
these relationships, and large-scale analyses are limited by the need for high
throughput, standardized scoring methods. To address these limitations, we
assessed whether automated image analysis of immunohistochemically stained tissue
microarrays can permit rapid, standardized scoring of tumour markers from
multiple studies. Tissue microarray sections prepared in nine studies containing
20 263 cores from 8267 breast cancers stained for two nuclear (oestrogen
receptor, progesterone receptor), two membranous (human epidermal growth factor
receptor 2 and epidermal growth factor receptor) and one cytoplasmic (cytokeratin
5/6) marker were scanned as digital images. Automated algorithms were used to
score markers in tumour cells using the Ariol system. We compared automated
scores against visual reads, and their associations with breast cancer survival.
Approximately 65-70% of tissue microarray cores were satisfactory for scoring.
Among satisfactory cores, agreement between dichotomous automated and visual
scores was highest for oestrogen receptor (Kappa = 0.76), followed by human
epidermal growth factor receptor 2 (Kappa = 0.69) and progesterone receptor
(Kappa = 0.67). Automated quantitative scores for these markers were associated
with hazard ratios for breast cancer mortality in a dose-response manner.
Considering visual scores of epidermal growth factor receptor or cytokeratin 5/6
as the reference, automated scoring achieved excellent negative predictive value
(96-98%), but yielded many false positives (positive predictive value = 30-32%).
For all markers, we observed substantial heterogeneity in automated scoring
performance across tissue microarrays. Automated analysis is a potentially useful
tool for large-scale, quantitative scoring of immunohistochemically stained
tissue microarrays available in consortia. However, continued optimization,
rigorous marker-specific quality control measures and standardization of tissue
microarray designs, staining and scoring protocols is needed to enhance results.
PMID- 27499892
TI - Differential expression of argininosuccinate synthetase in serous and non-serous
ovarian carcinomas.
AB - The current standard of care for epithelial ovarian cancer does not discriminate
between different histologic subtypes (serous, clear cell, endometrioid and
mucinous) despite the knowledge that ovarian carcinoma subtypes do not respond
uniformly to conventional platinum/taxane-based chemotherapy. Exploiting
addictions and vulnerabilities in cancers with distinguishable molecular features
presents an opportunity to develop individualized therapies that may be more
effective than the current 'one size fits all' approach. One such opportunity is
arginine depletion therapy with pegylated arginine deiminase, which has shown
promise in several cancer types that exhibit low levels of argininosuccinate
synthetase including hepatocellular and prostate carcinoma and melanoma. Based on
the high levels of argininosuccinate synthetase previously observed in ovarian
cancers, these tumours have been considered unlikely candidates for arginine
depletion therapy. However, argininosuccinate synthetase levels have not been
evaluated in the individual histologic subtypes of ovarian carcinoma. The current
study is the first to examine the expression of argininosuccinate synthetase at
the mRNA and protein levels in large cohorts of primary and recurrent ovarian
carcinomas and ovarian cancer cell lines. We show that the normal fallopian tube
fimbria and the majority of primary high-grade and low-grade serous ovarian
carcinomas express high levels of argininosuccinate synthetase, which tend to
further increase in recurrent tumours. In contrast to the serous subtype, non
serous ovarian carcinoma subtypes (clear cell, endometrioid and mucinous)
frequently lack detectable argininosuccinate synthetase expression. The in vitro
sensitivity of ovarian cancer cell lines to arginine depletion with pegylated
arginine deiminase was inversely correlated with argininosuccinate synthetase
expression. Our data suggest that the majority of serous ovarian carcinomas are
not susceptible to therapeutic intervention with arginine deiminase while a
subset of non-serous ovarian carcinoma subtypes are auxotrophic for arginine and
should be considered for clinical trials with pegylated arginine deiminase.
PMID- 27499893
TI - High CerS5 expression levels associate with reduced patient survival and
transition from apoptotic to autophagy signalling pathways in colorectal cancer.
AB - Ceramide synthase 5 is involved in the de novo synthesis of ceramide, a
sphingolipid involved in cell death and proliferation. In this study, we
investigated the role of ceramide synthase 5 in colorectal cancer by examining
ceramide synthase 5 expression, clinico-pathological parameters and association
with survival/death signalling pathways in cancer. Immunohistochemical analysis
of CerS5 was performed on 102 colorectal cancer samples using tissue microarrays
constructed from formalin-fixed and paraffin-embedded tissues. We found strong
membranous ceramide synthase 5 staining in 57 of 102 (56%) colorectal cancers. A
multivariate Cox regression analysis of ceramide synthase 5 expression adjusted
for disease stage, differentiation and lymphovascular invasion revealed reduced 5
year overall survival (p = 0.001) and 5-year recurrence-free survival (p =
0.002), with hazard ratios of 4.712 and 4.322, respectively. The effect of
ceramide synthase 5 expression on tumourigenic processes was further
characterised by reverse phase protein array analysis. Reverse phase protein
arrays were generated from laser capture microdissection-enriched carcinoma cells
from 19 fresh-frozen colorectal cancer tissues. Measurements of phosphorylation
and total levels of signalling proteins involved in apoptosis, autophagy and
other cancer-related pathways revealed two distinct signalling networks; weak
membranous ceramide synthase 5 intensity was associated with a proteomic network
dominated by signalling proteins linked to apoptosis, whereas strong ceramide
synthase 5 intensity was associated with a proteomic sub-network mostly composed
of proteins linked to autophagy. In conclusion, high ceramide synthase 5
expression was found in colorectal cancer tissue and was associated with poorer
patient outcomes. Our findings suggest that this may be mediated by a transition
from apoptotic to autophagy signalling pathways in ceramide synthase 5 High
expressing tumours, thus implicating ceramide synthase 5 in the progression of
colorectal cancer.
PMID- 27499894
TI - Novel association between microglia and stem cells in human gliomas: A
contributor to tumour proliferation?
AB - Brain tumour stem cells and microglia both promote the growth of astrocytomas,
the commonest form of primary brain tumour, with recent emerging evidence that
these cell types may interact in glioma models. It is unclear whether microglia
and stem cells are associated in human gliomas. To investigate this question, we
used the technique of tissue microarrays to perform a correlative study of a
large number of tumour samples. We quantified immunostaining of human astrocytic
tumour tissue microarrays (86 patients; World Health Organisation grade II-IV)
for microglia Ionized calcium binding adaptor molecule 1 (Iba1) and CD68, and
stem cell nestin, SOX2 and CD133. Ki67 was used to assess proliferation and GFAP
for astrocytic differentiation. Immunoreactivity for both microglial markers and
stem cell markers nestin and SOX2 significantly increased with increasing tumour
grade. GFAP was higher in low grade astrocytomas. There was a positive
correlation between: (i) both microglial markers and nestin and CD133, (ii)
nestin and tumour cell proliferation Ki67 and (iii) both microglial markers and
Ki67. SOX2 was not associated with microglia or tumour proliferation. To test the
clinical relevance, we investigated the putative association of these markers
with clinical outcomes. High expression for nestin and Iba1 correlated with
significantly shorter survival times, and high expression for nestin, Iba1, CD68
and Ki67 was associated with faster tumour progression on univariate analysis. On
multivariate analysis, nestin, CD133 and Ki67 remained significant predictors of
poorer survival, after adjustment for other markers. These results confirm
previous in vitro findings, demonstrating their functional relevance as a
therapeutic target in humans. This is the first report of a novel correlation
between microglia and stem cells that may drive human astrocytic tumour
development.
PMID- 27499895
TI - Metachronous pancreatic cancer originating from disseminated founder pancreatic
intraductal neoplasias (PanINs).
AB - Clonal populations originated from benign-looking 'founder cells' may spread
widely within pancreas instead of being localized in situ before frank pancreatic
ductal adenocarcinoma (PDA) can be detected. Metachronous PDA is not common
event, and we here sought to define potent origin of multiple PDAs developed in a
woman using advanced genetics technologies. Curative resection of pancreatic head
tumour was performed; however, 'recurrent' lesions in the remnant pancreas were
found 3.5 years later and total pancreatectomy was subsequently performed. The
metachronous lesions were morphologically similar to the primary PDA. Using a
next-generation sequencing and digital PCR, all three PDAs were shown to possess
rare somatic mutations in KRAS (p.T58I & p.Q61H). Curiously, identical KRAS
mutations were found in low-grade 'intraepithelial' lesions, which localized in
normal area of the pancreas and one of them possessed p53 mutation, which was
also found in the PDAs. The footprint of the tumour evolution marked by
mutational profiling supports a human correlate to the mouse models of
'dissemination' occurring at the earliest stages of pancreatic neoplasia.
PMID- 27499896
TI - Loss of ATRX and DAXX expression identifies poor prognosis for smooth muscle
tumours of uncertain malignant potential and early stage uterine leiomyosarcoma.
AB - Uterine smooth muscle tumours of uncertain malignant potential (STUMP) are
diagnostically and clinically challenging. The alternative lengthening of
telomeres (ALT) telomere maintenance mechanism is associated with poor survival
in soft tissue leiomyosarcoma. Time to first recurrence and survival were known
for 18 STUMP and 43 leiomyosarcomata (LMS). These were screened for ALT telomere
maintenance by the presence of ALT-associated PML bodies (APBs) and for changes
associated with the ALT phenotype, namely aberrant p53 expression, isocitrate
dehydrogenase 1 mutation (R132H substitution) expression, mutant ATRX
(alphathalassemia/mental retardation syndrome X-linked) expression and mutant
DAXX (death-domain-associated protein) expression by immunohistochemistry (IHC).
Overexpression of p16(INK4A) was examined immunohistologically in a subset of
cases. Many of the tumours associated with death or recurrence demonstrated APBs
commensurate with ALT telomere maintenance. However, all uterine STUMP (4/4), and
vaginal STUMP (2/2) patients, and almost all LMS patients (88.4%, 23/26,
including 90% (9/10) of stage 1 LMS cases), who had died of disease or who had
recurrent disease, displayed loss of ATRX or DAXX expression. Loss of ATRX or
DAXX expression identified poor prognosis (95% CI 2.1 to 40.8, p < 0.003), in the
LMS group. Thus, loss of ATRX or DAXX expression in uterine smooth muscle tumours
identifies a clinically aggressive molecular subtype of early stage LMS and when
histopathological features are problematic such as in STUMP. As ATRX and DAXX IHC
is readily performed in diagnostic laboratories these are potentially useful for
routine histopathological classification and management.
PMID- 27499897
TI - Clinical outcome in patients with peripherally-sited atypical lipomatous tumours
and dedifferentiated liposarcoma.
AB - The reported incidence of local recurrence of peripheral atypical lipomatous
tumours is highly variable and is likely to reflect the different inclusion
criteria of cases, and the design of previous studies. We aimed to study the
incidence of local recurrence of 90 cases of atypical lipomatous tumours and an
additional 18 cases of de novo dedifferentiated liposarcoma. All tumours were
diagnosed on the basis of MDM2 amplification: all patients had their first
treatment in the same specialist sarcoma unit and were followed for a minimum of
60 months. The tumours were diagnosed between 1997 and 2009 and followed until
the end of 2014. Seventy cases (78%) of atypical lipomatous tumours were located
in the thigh (mean size 195 mm on presentation). Eight atypical lipomatous
tumours (8.9%) recurred locally, of which 50% recurred after 60 months. The only
two tumours with intralesional excisions recurred. Seven of the eight recurrent
tumours were detected by the patient by self-examination. One case recurred a
second time as a dedifferentiated liposarcoma. Seventeen per cent of the de novo
dedifferentiated liposarcomas recurred within 60 months of presentation.
Extending the study period revealed that atypical lipomatous tumour could recur
up to 40 years after the first surgery. Furthermore, of 26 tumours that recurred
in the extended study, 27% recurred more than once, and three of the seven that
recurred more than once transformed into a dedifferentiated liposarcoma. We
recommend that, following post-operative wound care, patients with atypical
lipomatous tumour are referred back to their general practitioner for follow up,
but that in the event of a suspected recurrence they have rapid access back to
the specialist unit using a 'supported discharge' scheme. In the event of an
intralesional excision and if a lesion recurs, patients are followed in a
specialist unit at regular intervals: whether MRI scanning is a valuable means of
monitoring such patients is unclear and requires an evidence base.
PMID- 27499899
TI - ReadMax-a novel reading and scoring approach for EGFR gene copy number to predict
therapeutic benefit of erlotinib treatment in EGFR wild-type non-small-cell lung
cancer.
AB - EGFR mutation testing is now well established as a means of selecting the optimal
first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC).
However, deciding on the correct treatment for EGFR wild-type NSCLC remains a
challenge. EGFR fluorescence in-situ hybridization (FISH) testing of gene copy
number has been a promising marker, but has provided mixed results despite
attempts to standardize the reading and scoring process. The novel ReadMax
reading and scoring system focuses on the most aberrant cells, to identify
oncogene addiction, rather than taking a representative reading as in the
Colorado method. The methodology was developed using historical samples from the
TRUST and MERIT studies, followed by re-reading of the samples from the SATURN
trial. Analysis of samples using the ReadMax methodology revealed that
progression-free survival (PFS) and overall survival (OS) were improved in
patients with ReadMax FISH-positive (RM FISH+) tumours, compared with those whose
tumours were not RM FISH+: PFS hazard ratios (HRs) were 0.52 for RM FISH+ versus
0.93 for not RM FISH+; OS HRs were 0.69 and 0.92, respectively. For PFS, HR for
RM FISH+ versus not RM FISH+ in the SATURN erlotinib group was 0.53 (p = 0.003).
The PFS and OS results were also similar in the EGFR wild-type population (PFS
HRs were 0.63 and 0.96; OS HRs were 0.61 and 0.84, respectively), although
amplification of the EGFR gene in patients with EGFR wild-type disease was not
found to be predictive of treatment outcomes, which was unexpected but not
unprecedented. KRAS status was not found to affect outcomes. Further experience
is required to refine the ReadMax methodology and fully establish its validity
and robustness. In conclusion, the ReadMax scoring system to identify patients
with EGFR FISH-positive NSCLC is a promising technique, which could improve
treatment options and outcomes for patients with advanced NSCLC, in particular
for EGFR wild-type tumours.
PMID- 27499898
TI - Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to
osteoclast-rich mimics.
AB - Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were
recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and
by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the
high prevalence of these driver mutations, it may be possible to utilise these
alterations as diagnostic adjuncts in clinical practice. Here, we explored the
spectrum of H3.3 mutations in a wide range and large number of bone tumours (n =
412) to determine if these alterations could be used to distinguish GCT from
other osteoclast-rich tumours such as aneurysmal bone cyst, nonossifying fibroma,
giant cell granuloma, and osteoclast-rich malignant bone tumours and others. In
addition, we explored the driver landscape of GCT through whole genome, exome and
targeted sequencing (14 gene panel). We found that H3.3 mutations, namely
mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional
driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The
genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB.
Overall our observations suggest that the presence of H3F3A p.Gly34 mutations
does not entirely exclude malignancy in osteoclast-rich tumours. However, H3F3A
p.Gly34 mutations appear to be an almost essential feature of GCT that will aid
pathological evaluation of bone tumours, especially when confronted with small
needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of
GCT should be made with caution.
PMID- 27499900
TI - Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor
prognosis in myxoid liposarcoma.
AB - Myxoid liposarcoma is the second most common liposarcoma. Although myxoid
liposarcoma is relatively chemosensitive and thus a good candidate for
chemotherapy, cases with relapsed or metastatic disease still have poor outcome.
Here, we performed a gene microarray analysis to compare the gene expression
profiles in six clinical myxoid liposarcoma samples and three normal adipose
tissue samples, and to identify molecular biomarkers that would be useful as
diagnostic markers or treatment targets in myxoid liposarcoma. This showed that
the cancer-testis antigen PRAME was up-regulated in myxoid liposarcoma. We then
performed immunohistochemical, western blotting and real-time polymerase chain
reaction analyses to quantify the expression of PRAME and another cancer-testis
antigen, NY-ESO-1, in clinical samples of myxoid liposarcoma (n = 93),
dedifferentiated (n = 46), well-differentiated (n = 32) and pleomorphic
liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY-ESO-1
was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in
20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the
well-differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic
liposarcomas, respectively. High immunohistochemical expression of PRAME and/or
NY-ESO-1 was significantly correlated with tumour diameter, the existence of
tumour necrosis, a round-cell component of >5%, higher histological grade and
advanced clinical stage. High PRAME and NY-ESO-1 expression correlated
significantly with poor prognosis in a univariate analysis. The myxoid
liposarcomas showed significantly higher protein and mRNA expression levels of
PRAME and NY-ESO-1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and
NY-ESO-1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and
their high-level expression correlated with tumour grade and poor prognosis. Our
results support the potential use of PRAME and NY-ESO-1 as ancillary parameters
for differential diagnosis and as prognostic biomarkers, and indicate that the
development of immunotherapy against these cancer-testis antigens in myxoid
liposarcoma would be warranted.
PMID- 27499901
TI - A 12-gene signature to distinguish colon cancer patients with better clinical
outcome following treatment with 5-fluorouracil or FOLFIRI.
AB - Currently, there is no marker in use in the clinical management of colon cancer
to predict which patients will respond efficiently to 5-fluorouracil (5-FU), a
common component of all cytotoxic therapies. Our aim was to develop and validate
a multigene signature associated with clinical outcome from 5-FU therapy and to
determine if it could be used to identify patients who might respond better to
alternate treatments. Using a panel of 5-FU resistant and sensitive colon cancer
cell lines, we identified 103 differentially expressed genes providing us with a
5-FU response signature. We refined this signature using a clinically relevant
DNA microarray-based dataset of 359 formalin-fixed and paraffin-embedded (FFPE)
colon cancer samples. We then validated the final signature in an external
independent DNA microarray-based dataset of 316 stage III FFPE samples from the
PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial.
Finally, using a drug sensitivity database of 658 cell lines, we generated a list
of drugs that could sensitize 5-FU resistant patients using our signature. We
confirmed using the PETACC-3 dataset that the overall survival of subjects
responding well to 5-FU did not improve with the addition of irinotecan (FOLFIRI;
two-sided log-rank test p = 0.795). Conversely, patients who responded poorly to
5-FU based on our 12-gene signature were associated with better survival on
FOLFIRI therapy (one-sided log-rank test p = 0.039). This new multigene signature
is readily applicable to FFPE samples and provides a new tool to help manage
treatment in stage III colon cancer. It also provides the first evidence that a
subgroup of colon cancer patients can respond better to FOLFIRI than 5-FU
treatment alone.
PMID- 27499902
TI - In-depth molecular profiling of the biphasic components of uterine
carcinosarcomas.
AB - Uterine carcinosarcoma is a clinically aggressive malignancy composed of a mix of
carcinomatous and sarcomatous elements. We performed targeted next-generation
sequencing of 27 uterine cancer and sarcoma genes together with
immunohistochemical analyses of selected proteins in 30 uterine carcinosarcomas.
This included 13 cases in which the distinct carcinoma and sarcoma components
were sequenced separately and 10 cases where the metastatic tumours were analysed
in addition to the primary tumours. We identified non-synonymous somatic
mutations in 90% of the cases, with 27 of 30 cases (90%) harbouring TP53
alterations. The PI3K pathway was the most commonly mutated signalling pathway
with mutations identified in PIK3CA, PTEN, PIK3R1, and/or PIK3R2 in two-thirds of
the cases. Mutations in FBXW7, PPP2R1A, ARID1A and KRAS were demonstrated in a
minority of cases. In cases where the carcinomatous and sarcomatous components
were separately analysed, most of the mutations identified were present in both
components, indicating a common origin for the two components. Furthermore, the
same TP53 alterations and/or PI3K pathway mutations seen in the primary tumours
were also identified in the metastatic sites. Overall, carcinosarcomas exhibited
heterogeneous molecular features that resemble the heterogeneity seen in
endometrial carcinomas, with some showing endometrioid carcinoma-like and others
showing serous carcinoma-like mutation profiles. While patients with serous-like
tumours presented more frequently with advanced-stage disease compared to
patients with endometrioid-like tumours, there was no statistical difference in
outcome between the two groups. Our results provide insights into the oncogenesis
of uterine carcinosarcoma and identify targetable mutations that represent early
oncogenic events. The findings of the different molecular types of uterine
carcinosarcoma that parallel the different molecular types in endometrial
carcinoma may have future treatment implications with targeted therapies.
PMID- 27499903
TI - Increased proliferation in atypical hyperplasia/endometrioid intraepithelial
neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN
tumour suppressors.
AB - Uterine endometrioid carcinoma is the most common neoplastic disease in the
female genital tract and develops from a common precursor lesion, atypical
hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN). Although the genomic
landscape of endometrioid carcinoma has been recently revealed, the molecular
alterations that contribute to tumour progression from AH/EIN to carcinoma remain
to be elucidated. In this study, we used immunohistochemistry to determine if
loss of expression of two of the most commonly mutated tumour suppressors in
endometrioid carcinoma, PTEN and ARID1A, was associated with increased
proliferation in AH/EIN. We found that 80 (70%) of 114 cases exhibited decreased
or undetectable PTEN and 17 (15%) of 114 cases had focal loss of ARID1A staining.
ARID1A loss was focal, while PTEN loss was diffuse, and all specimens with ARID1A
loss had concurrent PTEN loss (p = 0.0003). Mapping the distribution of PTEN and
ARID1A staining in the same specimens demonstrated that all AH/EIN areas with
ARID1A loss were geographically nested within the areas of PTEN loss. A
significant increase in the proliferative activity was observed in areas of
AH/EIN with concurrent loss of PTEN and ARID1A compared to immediately adjacent
AH/EIN areas showing only PTEN loss. In a cell culture system, co-silencing of
ARID1A and PTEN in human endometrial epithelial cells increased cellular
proliferation to a greater degree than silencing either ARID1A or PTEN alone.
These results suggest an essential gatekeeper role for ARID1A that prevents PTEN
inactivation from promoting cellular proliferation in the transition of pre
cancerous lesions to uterine endometrioid carcinoma.
PMID- 27499905
TI - Somatic mutation in PIK3CA is a late event in cervical carcinogenesis.
AB - Somatic mutations in cervical intraepithelial neoplasia (CIN) are largely
unknown. Here, we profiled 35 cervical carcinomas and 23 CIN grade 2/3 (CIN2/3)
for mutations in 48 cancer-related genes using a Next Generation Sequencing-based
cancer panel. PIK3CA exon 9 was the most frequently mutated locus in cervical
carcinoma and the only mutated locus detected in CIN2/3. These PIK3CA exon 9
mutation findings were verified in a large, independent series (n = 647) covering
all stages of cervical carcinogenesis using high resolution melting-guided Sanger
sequencing. PIK3CA exon 9 mutation frequency was 37.1% (13/35; 95%CI 21.2-54.0%)
in cervical carcinoma, and 2.4% (5/209; 95%CI 0.5-4.7%) in CIN3. No PIK3CA exon 9
mutations were detected in CIN2 (0/144), CIN1 (0/154) and normal cervix (0/105).
In a third series of 46 CIN2/3 lesions from women with a known 5-year history of
preceding high-risk human papillomavirus (hrHPV) infection, detection of PIK3CA
exon 9 mutation was confined to 2 (5.4%; 95%CI 0.0-13.2%) CIN3 lesions with
preceding hrHPV infection >=5 years, and was absent in those with a short
duration (<5 years) of preceding hrHPV infection. In conclusion, somatic mutation
in PIK3CA represents a late event during cervical carcinogenesis, detected in a
substantial subset of cervical carcinoma, but only in a minority of CIN3.
PMID- 27499904
TI - The pathology and pathobiology of bicuspid aortic valve: State of the art and
novel research perspectives.
AB - Bicuspid aortic valve is the most prevalent cardiac valvular malformation. It is
associated with a high rate of long-term morbidity including development of
calcific aortic valve disease, aortic regurgitation and concomitant thoracic
aortic aneurysm and dissection. Recently, basic and translational studies have
identified some key processes involved in the development of bicuspid aortic
valve and its morbidity. The development of aortic valve disease and thoracic
aortic aneurysm and dissection is the result of complex interactions between
genotypes, environmental risk factors and specific haemodynamic conditions
created by bicuspid aortic valve anatomy. Herein, we review the pathobiology of
bicuspid aortic valve with a special emphasis on translational aspects of these
basic findings. Important but unresolved problems in the pathology of bicuspid
aortic valve and thoracic aortic aneurysm and dissection are discussed, along
with the molecular processes involved.
PMID- 27499906
TI - Biphasic components of sarcomatoid clear cell renal cell carcinomas are
molecularly similar to each other, but distinct from, non-sarcomatoid renal
carcinomas.
AB - Sarcomatoid transformation, wherein an epithelioid carcinomatous tumour component
coexists with a sarcomatoid histology, is a predictor of poor prognosis in clear
cell renal cell carcinoma. Our understanding of sarcomatoid change has been
hindered by the lack of molecular examination. Thus, we sought to characterize
molecularly the biphasic epithelioid and sarcomatoid components of sarcomatoid
clear cell renal cell carcinoma and compare them to non-sarcomatoid clear cell
renal cell carcinoma. We examined the transcriptome of the epithelioid and
sarcomatoid components of advanced stage sarcomatoid clear cell renal cell
carcinoma (n=43) and non-sarcomatoid clear cell renal cell carcinoma (n=37) from
independent discovery and validation cohorts using the cDNA microarray and RNA
seq platforms. We analyzed DNA copy number profiles, generated using SNP arrays,
from patients with sarcomatoid clear cell renal cell carcinoma (n=10) and
advanced non-sarcomatoid clear cell renal cell carcinoma (n=155). The epithelioid
and sarcomatoid components of sarcomatoid clear cell renal cell carcinoma had
similar gene expression and DNA copy number signatures that were, however,
distinct from those of high-grade, high-stage non-sarcomatoid clear cell renal
cell carcinoma. Prognostic clear cell renal cell carcinoma gene expression
profiles were shared by the biphasic components of sarcomatoid clear cell renal
cell carcinoma and the sarcomatoid component showed a partial epithelial-to
mesenchymal transition signature. Our genome-scale microarray-based transcript
data were validated in an independent set of sarcomatoid and non-sarcomatoid
clear cell renal cell carcinomas using RNA-seq. Sarcomatoid clear cell renal cell
carcinoma is molecularly distinct from non-sarcomatoid clear cell renal cell
carcinoma, with its genetic programming largely shared by its biphasic
morphological components. These data explain why a low percentage of sarcomatoid
histology augurs a poor prognosis; suggest the need to modify the pathological
grading system and introduce the potential for candidate biomarkers to detect
sarcomatoid change preoperatively without specifically sampling the histological
sarcomatoid component.
PMID- 27499907
TI - Classical pathology and mutational load of breast cancer - integration of two
worlds.
AB - Breast cancer is a complex molecular disease comprising several biological
subtypes. However, daily routine diagnosis is still based on a small set of well
characterized clinico-pathological variables. Here, we try to link the two worlds
of surgical pathology and multilayered molecular profiling by analyzing the
relationships between clinico-pathological phenotypes and mutational loads of
breast cancer. We evaluated the number of mutated genes with somatic non-silent
mutations in different subgroups of breast cancer based on clinico-pathological,
including immunohistochemical and tumour characteristics. The analysis was
performed for a cohort of 687 primary breast cancer patients with mutational
profiling, gene expression and clinico-pathological data available from The
Cancer Genome Atlas (TCGA) project. The number of mutated genes was strongly
positively associated with higher tumour grade (p = 1.4e-14) and with the
different immunohistochemical and PAM50 molecular subtypes of breast cancer (p =
1.4e-10 and p = 4.3e-10, respectively). We observed significant associations (|R|
> 0.4) between the abundance of mutated genes and expression levels of genes
related to proliferation in the overall cohort and hormone receptor positive
cohort, including the Recurrence Score gene signature (e.g., MYBL2 and BIRC5).
Specific mutated genes (TP53, NCOR1, NF1, PTPRD and RB1) were highly
significantly associated with high loads of mutated genes. Multivariate analysis
for overall survival (OS) revealed a worse survival for patients with high
numbers of mutated genes (hazard ratio = 4.6, 95% CI: 1.0 - 20.0, p = 0.044).
Here, we report a strong association of the number of mutated genes with
immunohistochemical and PAM50 subtypes and tumour grade in breast cancer. We
provide evidence that specific levels of the mutational load underlie different
morphological and biological phenotypes, which collectively constitute the
current basis of pathological diagnosis. Our study is a step towards genomics
informed breast pathology and will provide a basis for future studies in this
field bridging the gap between morphology, tumour biology and medical oncology.
PMID- 27499908
TI - HMGA2 expression distinguishes between different types of postpubertal testicular
germ cell tumour.
AB - The group of postpubertal testicular germ cell tumours encompasses lesions with
highly diverse differentiation - seminomas, embryonal carcinomas, yolk sac
tumours, teratomas and choriocarcinomas. Heterogeneous differentiation is often
present within individual tumours and the correct identification of the
components is of clinical relevance. HMGA2 re-expression has been reported in
many tumours, including testicular germ cell tumours. This is the first study
investigating HMGA2 expression in a representative group of testicular germ cell
tumours with the highly sensitive method of quantitative real-time PCR as well as
with immunohistochemistry. The expression of HMGA2 and HPRT was measured using
quantitative real-time PCR in 59 postpubertal testicular germ cell tumours.
Thirty specimens contained only one type of tumour and 29 were mixed neoplasms.
With the exception of choriocarcinomas, at least two pure specimens from each
subgroup of testicular germ cell tumour were included. In order to validate the
quantitative real-time PCR data and gather information about the localisation of
the protein, additional immunohistochemical analysis with an antibody specific
for HMGA2 was performed in 23 cases. Expression of HMGA2 in testicular germ cell
tumours depended on the histological differentiation. Seminomas and embryonal
carcinomas showed no or very little expression, whereas yolk sac tumours strongly
expressed HMGA2 at the transcriptome as well as the protein level. In teratomas,
the expression varied and in choriocarcinomas the expression was moderate. In
part, these results contradict data from previous studies but HMGA2 seems to
represent a novel marker to assist pathological subtyping of testicular germ cell
tumours. The results indicate a critical role in yolk sac tumours and some forms
of teratoma.
PMID- 27499909
TI - Regulation of macroautophagy in amiodarone-induced pulmonary fibrosis.
AB - Amiodarone (AD) is an iodinated benzofuran derivative, especially known for its
antiarrhythmic properties. It exerts serious side-effects even in patients
receiving low doses. AD is well-known to induce apoptosis of type II alveolar
epithelial cells (AECII), a mechanism that has been suggested to play an
important role in AD-induced lung fibrosis. The precise molecular mechanisms
underlying this disease are, however, still unclear. Because of its amphiphilic
nature, AD becomes enriched in the lysosomal compartments, affecting the general
functions of these organelles. Hence, in this study, we aimed to assess the role
of autophagy, a lysosome-dependent homeostasis mechanism, in driving AECII
apoptosis in response to AD. In vitro, AD-treated MLE12 and primary AECII cells
showed increased proSP-C and LC3B positive vacuolar structures and underwent LC3B
dependent apoptosis. In addition, AD-induced autophagosome-lysosome fusion and
increased autophagy flux were observed. In vivo, in C57BL/6 mice, LC3B was
localised at the limiting membrane of lamellar bodies, which were closely
connected to the autophagosomal structures in AECIIs. Our data suggest that AD
causes activation of macroautophagy in AECIIs and extensive autophagy-dependent
apoptosis of alveolar epithelial cells. Targeting the autophagy pathway may
therefore represent an attractive treatment modality in AD-induced lung fibrosis.
PMID- 27499910
TI - High expression of podoplanin in squamous cell carcinoma of the tongue occurs
predominantly in patients <=40 years but does not correlate with tumour spread.
AB - More than 30% of patients with squamous cell carcinoma (SCC) of the mobile tongue
have clinically undetectable lymph node metastasis. Tumour cells can spread as
single cells or collectively. A protein known to play a role in both processes is
podoplanin, which is expressed in endothelial cells not only in lymph vessels but
also in some aggressive tumours with high invasive and metastatic potential. Here
we studied samples from 129 patients with primary SCC of the tongue for
expression of podoplanin using immunohistochemistry. mRNA levels were analysed in
another 27 cases of tongue SCC with adjacent clinically tumour-free tongue tissue
and 14 tongue samples from healthy donors. Higher levels of podoplanin were seen
in tumours compared to both normal tongue and clinically normal tongue in the
tumour vicinity. No association was found between levels of podoplanin, presence
of lymph node metastases or other clinical factors. Patients aged 40 or less were
more likely to express high levels of podoplanin protein compared to older
patients (p = 0.027). We conclude that levels of podoplanin in primary tongue
SCCs are not associated with lymph node metastases. However, tongue SCCs arising
in young patients (<=40 years of age) are more likely to express high levels of
podoplanin than tongue SCCs that arise in the more elderly. The data suggest that
podoplanin has a distinctive role in young patients, who are known to have a poor
prognosis: these patients may, therefore, benefit from podoplanin inhibitory
therapies.
PMID- 27499911
TI - The molecular landscape of extraskeletal osteosarcoma: A clinicopathological and
molecular biomarker study.
AB - Extraskeletal osteosarcoma (ESOSA) is a rare soft tissue neoplasm representing
<5% of osteosarcomas and <1% of all soft-tissue sarcomas. Herein, we investigate
the clinicopathological and molecular features of ESOSA and explore potential
parameters that may affect outcome. Thirty-two cases were retrieved and
histomorphology was reviewed. Clinical history and follow-up were obtained
through electronic record review. DNA from formalin-fixed paraffin-embedded
(FFPE) tissue was extracted and processed from 27 cases. Genome-wide DNA copy
number (CN) alterations and allelic imbalances were analyzed by single nucleotide
polymorphism array using Affymetrix OncoScan FFPE Assay. Massive high-throughput
deep parallel sequencing was performed using a customized panel targeting 410
cancer genes. Log rank, Fisher's exact test and Cox proportional hazards were
used for statistical analysis. In this series of 32 patients (male n = 12, female
n = 20), the average age was 66 years (19-93) and median follow up was 24 months
(range 6-120 months). Frequent genomic alterations included CN losses in tumour
suppressor genes including CDKN2A (70%), TP53 (56%) and RB1 (49%). Mutations
affecting methylation/demethylation, chromatin remodeling and WNT/SHH pathways
were identified in 40%, 27%, and 27%, respectively. PIK3CA and TERT promoter
variant mutations were identified in 11% of the cases. Cases harbouring
simultaneous TP53 and RB1 biallelic CN losses were associated with worse overall
survival and local recurrence (p = 0.04, p = 0.02, respectively). CDKN2A losses
and positive margins were also associated with worse overall survival (p = 0.002;
p = 0.03, respectively). Our findings suggest that age above 60, positive margin
status, simultaneous biallelic TP53 and RB1 losses and CDKN2A loss are associated
with a worse outcome in ESOSA. Comparison between conventional paediatric
osteosarcoma and ESOSA shows that, while both share genetic similarities, there
are notable dissimilarities and mechanistic differences in the molecular pathways
involved in ESOSA.
PMID- 27499912
TI - The infiltration, and prognostic importance, of Th1 lymphocytes vary in molecular
subgroups of colorectal cancer.
AB - Giving strong prognostic information, T-cell infiltration is on the verge of
becoming an additional component in the routine clinical setting for
classification of colorectal cancer (CRC). With a view to further improving the
tools for prognostic evaluation, we have studied how Th1 lymphocyte infiltration
correlates with prognosis not only by quantity, but also by subsite, within CRCs
with different molecular characteristics (microsatellite instability, CpG island
methylator phenotype status, and BRAF and KRAS mutational status). We evaluated
the Th1 marker T-bet by immunohistochemistry in 418 archival tumour tissue
samples from patients who underwent surgical resection for CRC. We found that a
high number of infiltrating Th1 lymphocytes is strongly associated with an
improved prognosis in patients with CRC, irrespective of intratumoural subsite,
and that both extent of infiltration and patient outcome differ according to
molecular subgroup. In brief, microsatellite instability, CpG island methylator
phenotype-high and BRAF mutated tumours showed increased infiltration of Th1
lymphocytes, and the most pronounced prognostic effect of Th1 infiltration was
found in these tumours. Interestingly, BRAF mutated tumours were found to be more
highly infiltrated by Th1 lymphocytes than BRAF wild-type tumours whereas the
opposite was seen for KRAS mutated tumours. These differences could be explained
at least partly by our finding that BRAF mutated, in contrast to KRAS mutated,
CRC cell lines and tumour specimens expressed higher levels of the Th1-attracting
chemokine CXCL10, and reduced levels of CCL22 and TGFB1, stimulating Th2/Treg
recruitment and polarisation. In conclusion, the strong prognostic importance of
Th1 lymphocyte infiltration in CRC was found at all subsites evaluated, and it
remained significant in multivariable analyses, indicating that T-bet may be a
valuable marker in the clinical setting. Our results also indicate that T-bet is
of value when analysed in molecular subgroups of CRC, allowing identification of
patients with especially poor prognosis who are in need of extended treatment.
PMID- 27499913
TI - Genotyping confirms inheritance of the rare At(a-) type in a case of haemolytic
disease of the newborn.
AB - The At(a) blood group antigen (now AUG2 in the Augustine system) is a high
frequency antigen with negative phenotype At(a-) found only in individuals of
African ancestry. In a twin pregnancy, the fifth pregnancy in a woman of African
origin, serological investigations confirmed that the mother was At(a-) and anti
At(a) was detected. DNA samples were exome sequenced and alignment was performed
to allow variant calling. It was confirmed that the single nucleotide
polymorphism, rs45458701, within the SLC29A1 gene encoding the ENT1 protein,
recently reported to be a basis of the At(a-) phenotype was also the basis of the
phenotype in this family. The reagents for serological analysis required to
identify the rare blood type present in this mother are held in only a few
reference laboratories worldwide. This case highlights the utility of genetic
methods in resolving complex investigations involving blood grouping and
demonstrates that genotyping of variants associated with blood types present in
specific ethnic groups may be the fastest method available for identification of
the basis of fetomaternal incompatibilities.
PMID- 27499914
TI - Nottingham Prognostic Index Plus: Validation of a clinical decision making tool
in breast cancer in an independent series.
AB - The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in
breast cancer (BC) that aims to provide improved patient outcome stratification
superior to the traditional NPI. This study aimed to validate the NPI+ in an
independent series of BC. Eight hundred and eighty five primary early stage BC
cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers
[Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6,
CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin
1] using immunohistochemistry and classified into biological classes by fuzzy
logic-derived algorithms previously developed in the Nottingham series.
Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using
bespoke NPI-like formulae, previously developed in each NPI+ biological class of
the Nottingham series, utilising clinicopathological parameters: number of
positive nodes, pathological tumour size, stage, tubule formation, nuclear
pleomorphism and mitotic counts. Biological classes and PGs were compared between
the Edinburgh and Nottingham series using Cramer's V and their role in patient
outcome prediction using Kaplan-Meier curves and tested using Log Rank. The NPI+
biomarker panel classified the Edinburgh series into seven biological classes
similar to the Nottingham series (p > 0.01). The biological classes were
significantly associated with patient outcome (p < 0.001). PGs were comparable in
predicting patient outcome between series in Luminal A, Basal p53 altered,
HER2+/ER+ tumours (p > 0.01). The good PGs were similarly validated in Luminal B,
Basal p53 normal, HER2+/ER- tumours and the poor PG in the Luminal N class (p >
0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N,
Luminal B, Basal p53 normal and HER2+/ER- classes could not be validated. This
study demonstrates the reproducibility of NPI+ and confirmed its prognostic value
in an independent cohort of primary BC. Further validation in large randomised
controlled trial material is warranted.
PMID- 27499915
TI - FMNL2/FMNL3 formins are linked with oncogenic pathways and predict melanoma
outcome.
AB - While most early (stage I-II) melanomas are cured by surgery, recurrence is not
uncommon. Prognostication by current clinicopathological parameters does not
provide sufficient means for identifying patients who are at risk of developing
metastases and in need of adjuvant therapy. Actin-regulating formins may account
for invasive properties of cancer cells, including melanoma. Here, we studied
formin-like protein 2 and 3 (FMNL2 and FMNL3) in melanoma by analysing their role
in the invasive properties of melanoma cells and by evaluating whether FMNL2
expression is associated with melanoma outcome. Immunohistochemical
characterization of FMNL2 in a cohort of 175 primary cutaneous stage I-II
melanomas indicated that high FMNL2 reactivity correlates with poor outcome as
evaluated by recurrence free survival (p < 0.0001) or disease specific survival
(p < 0.0001). In multivariate analysis, Breslow's thickness (p < 0.05) and FMNL2
expression (p < 0.001) remained as independent prognostic factors. Cellular
studies revealed that FMNL2 is a component of filopodia in many melanoma cell
lines. Inhibition of either FMNL2 or the closely related FMNL3 affected the
maintenance of melanoma cell morphology and reduced migration. Finally,
inhibition of the BRAF, PI3K and MAPK oncogenic pathways markedly reduced
expression of both FMNL2 and FMNL3 in melanoma cells. The results suggest a major
role for FMNL2/FMNL3 formins in melanoma biology and raise the possibility that
the novel targeted melanoma drugs may interfere with the cellular properties
regulated by these formins.
PMID- 27499916
TI - HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment
in mesenchymal tumours and is associated with response to vorinostat.
AB - Histone deacetylases (HDAC) are key players in epigenetic regulation of gene
expression and HDAC inhibitor (HDACi) treatment seems to be a promising
anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b
has been shown to be a potential biomarker for sensitivity to HDACi therapy in
cutaneous T-cell lymphoma and hepatocellular carcinoma. We aimed to evaluate
HR23b as a candidate biomarker for HDACi response in sarcomas and
gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed
comprehensively by western blot in sarcoma and GIST cell lines covering all major
clinically relevant subtypes. MTT assay and ApoTox-Glo(TM) Triplex assay were
performed after treatment with vorinostat, belinostat, mocetinostat and
entinostat. HR23b protein expression was measured under HDACi treatment.
Furthermore, HR23b expression levels were immunohistochemically determined in a
large set of 523 clinical samples from sarcoma and GIST patients. Western blot
analyses showed that sarcomas differ significantly in their expression of HR23b
protein. All HDACi were able to regulate proliferation and apoptosis in vitro.
Sensitivity to vorinostat correlated significantly with HR23b protein expression.
Immunohistochemical prevalence screening in clinical samples of relevant adult
type tumours revealed that 12.5% of sarcomas (among them malignant peripheral
nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated
liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high
HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic
effects in sarcomas depending on the expression level of HR23b. These findings
suggest that HR23b represents a candidate biomarker for HDACi sensitivity in
certain sarcoma types and in GIST.
PMID- 27499917
TI - The pathological and biochemical identification of possible seed-lesions of
transmitted transthyretin amyloidosis after domino liver transplantation.
AB - The most serious issue in domino liver transplantation (DLT) using liver grafts
from patients with transthyretin (TTR)-related familial amyloid polyneuropathy
(FAP) is the development of iatrogenic transmitted amyloidosis (de novo
amyloidosis) in DLT-recipients. However, little is known regarding the mechanisms
of the initial stage of amyloid formation in these recipients. We detected
initial lesions (possible seed-lesions) of this iatrogenic amyloidosis in two
recipients following liver grafting from FAP patients. Patient 1 underwent DLT at
age 65 from an FAP patient with a Val30Met TTR variant and patient 2 received DLT
from an FAP patient with a Val30Leu TTR variant at age 32. Patient 2 was started
on diflunisal administration from 4 years after DLT. While neither patient had
symptoms of FAP, small amyloid deposits were detected on the gastroduodenal
mucosae 14 months and 12 years after DLT in patient 1 and patient 2,
respectively. The amyloid was analyzed using a laser microdissection system and
tandem mass spectrometry. Biochemical analysis indicated that the amyloid was
composed mostly of variant TTR produced from the transplanted liver in both
patients. In patient 1, wild-type TTR amyloid was detectable in the duodenal
mucosa obtained 2 years after DLT. This is the first study to successfully
capture the pathological and biochemical features of initial-stage amyloid
lesions in DLT recipients. The findings clearly indicate that amyloid deposition
can start by deposition of variant TTR followed by deposition of wild-type TTR,
and blocking of amyloid seed formation from variant TTR may be a key to prevent
or delay the development of DLT-associated amyloidosis.
PMID- 27499918
TI - Gene expression analysis of biopsy samples reveals critical limitations of
transcriptome-based molecular classifications of hepatocellular carcinoma.
AB - Molecular classification of hepatocellular carcinomas (HCC) could guide patient
stratification for personalized therapies targeting subclass-specific cancer
'driver pathways'. Currently, there are several transcriptome-based molecular
classifications of HCC with different subclass numbers, ranging from two to six.
They were established using resected tumours that introduce a selection bias
towards patients without liver cirrhosis and with early stage HCCs. We generated
and analyzed gene expression data from paired HCC and non-cancerous liver tissue
biopsies from 60 patients as well as five normal liver samples. Unbiased
consensus clustering of HCC biopsy profiles identified 3 robust classes. Class
membership correlated with survival, tumour size and with Edmondson and Barcelona
Clinical Liver Cancer (BCLC) stage. When focusing only on the gene expression of
the HCC biopsies, we could validate previously reported classifications of HCC
based on expression patterns of signature genes. However, the subclass-specific
gene expression patterns were no longer preserved when the fold-change relative
to the normal tissue was used. The majority of genes believed to be subclass
specific turned out to be cancer-related genes differentially regulated in all
HCC patients, with quantitative rather than qualitative differences between the
molecular subclasses. With the exception of a subset of samples with a definitive
beta-catenin gene signature, biological pathway analysis could not identify class
specific pathways reflecting the activation of distinct oncogenic programs. In
conclusion, we have found that gene expression profiling of HCC biopsies has
limited potential to direct therapies that target specific driver pathways, but
can identify subgroups of patients with different prognosis.
PMID- 27499919
TI - Molecular classification of thyroid lesions by combined testing for miRNA gene
expression and somatic gene alterations.
AB - Multiple molecular markers contribute to the pathogenesis of thyroid cancer and
can provide valuable information to improve disease diagnosis and patient
management. We performed a comprehensive evaluation of miRNA gene expression in
diverse thyroid lesions (n = 534) and developed predictive models for the
classification of thyroid nodules, alone or in combination with genotyping.
Expression profiling by reverse transcription-quantitative polymerase chain
reaction in surgical specimens (n = 257) identified specific miRNAs
differentially expressed in 17 histopathological categories. Eight supervised
machine learning algorithms were trained to discriminate benign from malignant
lesions and evaluated for accuracy and robustness. The selected models showed
invariant area under the receiver operating characteristic curve (AUC) in cross
validation (0.89), optimal AUC (0.94) in an independent set of preoperative
thyroid nodule aspirates (n = 235), and classified 92% of benign lesions as low
risk/negative and 92% of malignant lesions as high risk/positive. Surgical and
preoperative specimens were further tested for the presence of 17 validated
oncogenic gene alterations in the BRAF, RAS, RET or PAX8 genes. The miRNA-based
classifiers complemented and significantly improved the diagnostic performance of
the 17-mutation panel (p < 0.001 for McNemar's tests). In a subset of resected
tissues (n = 54) and in an independent set of thyroid nodules with indeterminate
cytology (n = 42), the optimized ThyraMIR Thyroid miRNA Classifier increased
diagnostic sensitivity by 30-39% and correctly classified 100% of benign nodules
negative by the 17-mutation panel. In contrast, testing with broad targeted next
generation sequencing panels decreased diagnostic specificity by detecting
additional mutations of unknown clinical significance in 19-39% of benign
lesions. Our results demonstrate that, independent of mutational status, miRNA
expression profiles are strongly associated with altered molecular pathways
underlying thyroid tumorigenesis. Combined testing for miRNA gene expression and
well-established somatic gene alterations is a novel diagnostic strategy that can
improve the preoperative diagnosis and surgical management of patients with
indeterminate thyroid nodules.
PMID- 27499920
TI - Fluorescence imaging to localize head and neck squamous cell carcinoma for
enhanced pathological assessment.
AB - Accurately identifying close or positive margins in real-time permits re-excision
during surgical procedures. Intraoperative assessment of margins via gross
examination and frozen section is a widely used tool to assist the surgeon in
achieving complete resection. While this methodology permits diagnosis of freshly
resected tissue, the process is fraught with misinterpretation and sampling
errors. During fluorescence-guided surgery, an exogenous fluorescent agent
specific for the target disease is imaged in order to navigate the surgical
excision. As this technique quickly advances into the clinic, we hypothesize that
the disease-specific fluorescence inherently contained within the resected
tissues can be used to guide histopathological assessment. To evaluate the
feasibility of fluorescence-guided pathology, we evaluated head and neck squamous
cell carcinoma tumour specimens and margins resected from animals and patients
after systemic injection of cetuximab-IRDye800CW. In a preclinical model of
luciferase-positive tumour resection using bioluminescence as the gold standard,
fluorescence assessment determined by closed-field fluorescence imaging of fresh
resected margins accurately predicted the presence of disease in 33/39 positive
margins yielding an overall sensitivity of 85%, specificity of 95%, positive
predictive value (PPV) of 94%, and a negative predictive value (NPV) of 87%,
which was superior to both surgical assessment (54%, 61%, 57%, and 58%) and
pathological assessment (49%, 95%, 91%, and 66%), respectively. When the power of
the technique was evaluated using human-derived tumour tissues, as little as
0.5mg (1mm(3)) of tumour tissue was identified (tumour-to-background-ratio:5.2).
When the sensitivity/specificity of fluorescence-guided pathology was determined
using traditional histological assessment as the gold standard in human tissues
obtained during fluorescence-guided surgery, the technique was highly accurate
with a sensitivity of 91%, specificity of 85%, PPV of 81%, and NPV of 93% for 90
human-derived samples. This approach can be used as a companion to the
pathologist, eliminating confounding factors while impacting surgical
intervention and patient management.
PMID- 27499922
TI - The molecular characteristics of colonic neoplasms in serrated polyposis: a
systematic review and meta-analysis.
AB - Serrated polyposis is a rare disorder characterised by the presence of multiple
serrated polyps in the large intestine, and an increased personal and familial
risk of colorectal cancer. Knowledge of the molecular characteristics of colonic
lesions which develop in this syndrome is fragmented, making it difficult to
understand the underlying genetic basis of this condition. We conducted a
systematic review and meta-analysis of all studies which evaluated the molecular
characteristics of colorectal neoplasms found in individuals with serrated
polyposis. We identified 4561 potentially relevant studies, but due to a lack of
consensus in the reporting of findings, only fourteen studies were able to be
included in the meta-analysis. BRAF mutation was found in 73% (95% CI 65-80%) of
serrated polyps, 0% (95% CI 0-3%) of conventional adenomas and 49% (95%CI 33-64%)
of colorectal cancers. In contrast, KRAS mutation was present in 8% (95% CI 5
11%) of serrated polyps, 3% (95% CI 0-13%) of conventional adenomas and 6% (95%
CI 0-13%) of colorectal cancers. Absence of MLH1 immunostaining was found in 3%
(95% CI 0-10%) of serrated polyps and 53% (95% CI 36-71%) of colorectal cancers.
Overall, microsatellite instability was found in 40% (95% CI 18-64%) of
colorectal cancers arising in the setting of serrated polyposis. Our results
indicate that diverse molecular pathways are likely to contribute to the
increased predisposition for colorectal cancer in individuals with serrated
polyposis. We also propose a set of minimum standards for the reporting of future
research in serrated polyposis as this is a rare syndrome and collation of
research findings from different centres will be essential to identify the
molecular mechanisms involved in the pathogenesis of this condition.
PMID- 27499921
TI - Inflammatory response in serrated precursor lesions of the colon classified
according to WHO entities, clinical parameters and phenotype-genotype
correlation.
AB - Studies on traditional serrated adenoma (TSA) and sessile serrated adenoma with
dysplasia (SSA-D) are rare due to the low frequency of these lesions, which are
well defined by the latest WHO classification. However, introducing new
morphological criteria such as intra-epithelial lymphocytes (IELs) might
facilitate colorectal polyp diagnoses. Additionally, the phenotype-genotype
correlation needs to be updated as the terminology has repeatedly changed. This
study analysed 516 polyps, consisting of 118 classical adenomas (CAD), 116
hyperplastic polyps (HPP), 179 SSAs, 41 SSA-Ds, and 62 TSAs. The lesions were
analysed in relation to the patients' clinical parameters including gender, age,
localisation, and size. The inflammatory background of the polyps was quantified
and BRAF and KRAS mutations as well as MLH1 and CDKN2A promoter methylation were
assessed. In multivariate analyses, an increase in IELs was an independent and
robust new criterion for the diagnosis of SSA-D (p < 0.001). Superficial erosions
and acute neutrophil granulocytes led to reactive changes potentially resembling
dysplasia. KRAS and BRAF mutations were associated with CAD/TSA and HPP/SSA,
respectively. However, almost half of TSAs had a BRAF mutation and were KRAS wild
type. CDKN2A seems to precede MLH1 hyper-methylation within the serrated
carcinogenesis model. The genotyping of WHO-based entities - and especially SSA -
has sharpened in comparison to previously published data. TSAs can be sub-grouped
according to their mutation status. Of note, the higher number of IELs in SSA-D
reflects their close relationship to colorectal cancers with micro-satellite
instability. Therefore, IELs might represent a new diagnostic tool for SSA-D.
PMID- 27499924
TI - Novel translational model of resolving inflammation triggered by UV-killed E.
coli.
AB - Whilst numerous studies investigating the aetiology of inflammatory diseases have
been performed in rodents, the applicability of these data to human
pathophysiology is frequently debated. Regardless of the strengths and weaknesses
of rodent models in biomedical research, there is a need to develop models of
experimental inflammation in humans. Here, we describe a self-resolving acute
inflammatory response triggered by the intradermal injection of UV-killed
Escherichia coli into the forearm of healthy volunteers. Cells and exudates were
harvested from onset to resolution by applying negative pressure over the
inflamed site. Onset was characterized by high blood flow, neutrophilia and peak
levels of pro-inflammatory cytokines, whilst resolution showed a decline in blood
blow, reduction in neutrophils, increase in monocytes/macrophages and waning of
classic pro-inflammatory cytokine levels. An anti-inflammatory effect, defined as
suppression of onset phase events, was demonstrated by administering naproxen, a
conventional non-steroidal anti-inflammatory drug. In summary, this model of
resolving acute inflammation is minimally invasive, highly tractable and allows
simultaneous investigation of the vascular response, cellular trafficking and
chemical mediator profile of onset and resolution phases of acute inflammation in
humans. It can serve as a translational platform to provide mechanistic insights
and to test the clinical efficacy of novel anti-inflammatory and pro-resolving
drugs, and also as a tool in patients to explore inherent defects in resolution
pathways.
PMID- 27499923
TI - High-throughput automated scoring of Ki67 in breast cancer tissue microarrays
from the Breast Cancer Association Consortium.
AB - Automated methods are needed to facilitate high-throughput and reproducible
scoring of Ki67 and other markers in breast cancer tissue microarrays (TMAs) in
large-scale studies. To address this need, we developed an automated protocol for
Ki67 scoring and evaluated its performance in studies from the Breast Cancer
Association Consortium. We utilized 166 TMAs containing 16,953 tumour cores
representing 9,059 breast cancer cases, from 13 studies, with information on
other clinical and pathological characteristics. TMAs were stained for Ki67 using
standard immunohistochemical procedures, and scanned and digitized using the
Ariol system. An automated algorithm was developed for the scoring of Ki67, and
scores were compared to computer assisted visual (CAV) scores in a subset of 15
TMAs in a training set. We also assessed the correlation between automated Ki67
scores and other clinical and pathological characteristics. Overall, we observed
good discriminatory accuracy (AUC = 85%) and good agreement (kappa = 0.64)
between the automated and CAV scoring methods in the training set. The
performance of the automated method varied by TMA (kappa range= 0.37-0.87) and
study (kappa range = 0.39-0.69). The automated method performed better in
satisfactory cores (kappa = 0.68) than suboptimal (kappa = 0.51) cores (p-value
for comparison = 0.005); and among cores with higher total nuclei counted by the
machine (4,000-4,500 cells: kappa = 0.78) than those with lower counts (50-500
cells: kappa = 0.41; p-value = 0.010). Among the 9,059 cases in this study, the
correlations between automated Ki67 and clinical and pathological characteristics
were found to be in the expected directions. Our findings indicate that automated
scoring of Ki67 can be an efficient method to obtain good quality data across
large numbers of TMAs from multicentre studies. However, robust algorithm
development and rigorous pre- and post-analytical quality control procedures are
necessary in order to ensure satisfactory performance.
PMID- 27499925
TI - Somatic mutation profiles in primary colorectal cancers and matching ovarian
metastases: Identification of driver and passenger mutations.
AB - The mutational profiles of primary colorectal cancers (CRCs) and corresponding
ovarian metastases were compared. Using a custom-made next generation sequencing
panel, 115 cancer-driving genes were analyzed in a cohort of 26 primary CRCs and
30 matching ovarian metastases (four with bilateral metastases). To obtain a
complete overview of the mutational profile, low thresholds were used in
bioinformatics analysis to prevent low frequency passenger mutations from being
filtered out. A subset of variants was validated using Sanger and/or hydrolysis
probe assays. The mutational landscape of CRC that metastasized to the ovary was
not strikingly different from CRC in consecutive series. When comparing primary
CRCs and their matching ovarian metastases, there was considerable overlap in the
mutations of early affected genes. A subset of mutations demonstrated less
overlap, presumably being passenger mutations. In particular, primary CRCs showed
a substantially high number of passenger mutations. We also compared the primary
CRCs and matching metastases for stratifying variants of six genes (KRAS, NRAS,
BRAF, FBXW7, PTEN and PIK3CA) that select for established (EGFR directed) or
future targeted therapies. In a total of 31 variants 12 were not found in either
of the two locations. Tumours thus differed in the number of discordant variants
between the primary tumours and matching metastases. Half of these discordant
variants were definitive class 4/5 pathogenic variants. However, in terms of
temporal heterogeneity, no clear relationship was observed between the number of
discordant variants and the time interval between primary CRCs and the detection
of ovarian metastases. This suggests that dormant metastases may be present from
the early days of the primary tumours.
PMID- 27499926
TI - Rapid and reliable diagnosis of Wilson disease using X-ray fluorescence.
AB - Wilson's disease (WD) is a rare autosomal recessive disease due to mutations of
the gene encoding the copper-transporter ATP7B. The diagnosis is hampered by the
variability of symptoms induced by copper accumulation, the inconstancy of the
pathognomonic signs and the absence of a reliable diagnostic test. We
investigated the diagnostic potential of X-ray fluorescence (XRF) that allows
quantitative analysis of multiple elements. Studies were performed on animal
models using Wistar rats (n = 10) and Long Evans Cinnamon (LEC) rats (n = 11),
and on human samples including normal livers (n = 10), alcohol cirrhosis (n = 8),
haemochromatosis (n = 10), cholestasis (n = 6) and WD (n = 22). XRF experiments
were first performed using synchrotron radiation to address the elemental
composition at the cellular level. High-resolution mapping of tissue sections
allowed measurement of the intensity and the distribution of copper, iron and
zinc while preserving the morphology. Investigations were further conducted using
a laboratory X-ray source for irradiating whole pieces of tissue. The sensitivity
of XRF was highlighted by the discrimination of LEC rats from wild type even
under a regimen using copper deficient food. XRF on whole formalin-fixed paraffin
embedded needle biopsies allowed profiling of the elements in a few minutes. The
intensity of copper related to iron and zinc significantly discriminated WD from
other genetic or chronic liver diseases with 97.6% specificity and 100%
sensitivity. This study established a definite diagnosis of Wilson's disease
based on XRF. This rapid and versatile method can be easily implemented in a
clinical setting.
PMID- 27499927
TI - Increased MMP-7 expression in biliary epithelium and serum underpins native liver
fibrosis after successful portoenterostomy in biliary atresia.
AB - The molecular mechanisms underlying progressive liver fibrosis following surgical
treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic
gene and protein expression and serum levels of matrix metalloproteinases (MMPs)
and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and
relate them to histological signs of liver injury, clinical follow-up data and
biochemical markers of hepatic function. LIver biopsies and serum samples were
obtained from 25 children after successful PE at median age of 3.3 years. Serum
MMP concentrations were determined by enzyme-linked immune sorbent assay. Hepatic
gene expression of MMPs and TIMPs was analyzed using real-time reverse
transcription PCR. Liver expression of MMP-7 and cytokeratin-7 was studied using
immunohistochemistry. Despite effective clearance of biochemical and histological
cholestasis following PE, BA patients showed increased hepatic gene expression of
MMP-7 (29-fold, p < 0.001), MMP-2 (3.1-fold, p < 0.001), MMP-14 (1.7-fold, p =
0.007), and TIMP-1 (1.8-fold, p < 0.001), when compared to controls. Similar to a
biliary epithelial marker cytokeratin-7, expression of MMP-7 localized in biliary
epithelium of bile ducts and ductal proliferations and periportal hepatocytes and
was increased (p < 0.001) in relation to controls. BA patients had 6-fold higher
serum levels of MMP-7 (p < 0.001), which correlated positively with hepatic MMP-7
gene (r = 0.548, p = 0.007) and protein (r = 0.532, p = 0.007) expression.
Patients showed a positive correlation between biliary MMP-7 expression and
Metavir fibrosis stage (r = 0.605, p = 0.001) and portal fibrosis grade (r =
0.606, p = 0.001). Neither similarly increased MMP-7 expression nor correlation
with liver fibrosis was observed in patients with intestinal failure-associated
liver disease and comparable Metavir stage. In conclusion, our findings support
an unique role of altered hepatic expression of MMP-7 in the progression of liver
fibrosis after successful PE and introduce a potential therapeutic target to
pharmacologically extend native liver survival by inhibiting MMP-7 hyperactivity.
Serum MMP-7 may be a valuable postoperative prognostic tool in BA.
PMID- 27499928
TI - Who's afraid of response bias?
AB - Response bias (or criterion) contamination is insidious in studies of
consciousness: that observers report they do not see a stimulus may not mean they
have absolutely no subjective experience; they may be giving such reports in
relative terms in the context of other stimuli. Bias-free signal detection
theoretic measures provide an excellent method for avoiding response bias
confounds, and many researchers correctly adopt this approach. However, here we
discuss how a fixation on avoiding criterion effects can also be misleading and
detrimental to fruitful inquiry. In a recent paper, Balsdon and Azzopardi
(Absolute and relative blindsight. Consciousness and Cognition 2015; 32:79-91.)
claimed that contamination by response bias led to flawed findings in a previous
report of "relative blindsight". We argue that their criticisms are unfounded.
They mistakenly assumed that others were trying (and failing) to apply their
preferred methods to remove bias, when there was no such intention. They also
dismissed meaningful findings because of their dependence on criterion, but such
dismissal is problematic: many real effects necessarily depend on criterion.
Unfortunately, these issues are technically tedious, and we discuss how they may
have confused others to misapply psychophysical metrics and to draw questionable
conclusions about the nature of TMS (transcranial magnetic stimulation)-induced
blindsight. We conclude by discussing the conceptual importance of criterion
effects in studies of conscious awareness: we need to treat them carefully, but
not to avoid them without thinking.
PMID- 27499929
TI - The signal processing architecture underlying subjective reports of sensory
awareness.
AB - What is the relationship between perceptual information processing and subjective
perceptual experience? Empirical dissociations between stimulus identification
performance and subjective reports of stimulus visibility are crucial for
shedding light on this question. We replicated a finding that metacontrast
masking can produce such a dissociation (Lau and Passingham, 2006), and report a
novel finding that this paradigm can also dissociate stimulus identification
performance from the efficacy with which visibility ratings predict task
performance. We explored various hypotheses about the relationship between
perceptual task performance and visibility rating by implementing them in
computational models and using formal model comparison techniques to assess which
ones best captured the unusual patterns in the data. The models fell into three
broad categories: Single Channel models, which hold that task performance and
visibility ratings are based on the same underlying source of information; Dual
Channel models, which hold that there are two independent processing streams that
differentially contribute to task performance and visibility rating; and
Hierarchical models, which hold that a late processing stage generates visibility
ratings by evaluating the quality of early perceptual processing. Taking into
account the quality of data fitting and model complexity, we found that
Hierarchical models perform best at capturing the observed behavioral
dissociations. Because current theories of visual awareness map well onto these
different model structures, a formal comparison between them is a powerful
approach for arbitrating between the different theories.
PMID- 27499930
TI - Strong correlation between lung ultrasound and chest computerized tomography
imaging for the detection of acute lung injury/acute respiratory distress
syndrome in rats.
AB - BACKGROUND: Lung ultrasound (LUS) is a clinical imaging technique for diagnosing
acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In humans
and several large animals, LUS demonstrates similar specificity and sensitivity
to computerized tomography (CT) scanning. Current study evaluated the degree of
agreement between LUS and CT imaging in characterizing ALI/ARDS in rats. METHODS:
Thirty male Sprague-Dawley rats were imaged by LUS before randomization into
three groups to receive intratracheal saline, 3 or 6 mg/kg LPS respectively
(n=10). LUS and CT imaging was conducted 2 hours after instillation. Cross table
analyses and kappa statistics were used to determine agreement levels between LUS
and CT assessments of lung condition. RESULTS: Before instillation, rats
presented with a largely A-pattern in LUS images, however, a significantly
increase B-lines were observed in all groups after instillation and showed dose
response to LPS or to saline. One rat treated with 6 mg/kg lipopolysaccharide
(LPS) presented with lung consolidation. The agreement between the LUS and the CT
in detecting the main characteristics of ALI/ARDS in rat was strong (r=0.758,
P<0.01, k=0.737). CONCLUSIONS: In conclusion, LUS detects ALI/ARDS with high
agreement with micro PET/CT scanning in a rat model, suggesting that LUS
represents a positive refinement in rat ALI/ARDS disease models.
PMID- 27499931
TI - Positive expression of protein chromosome 9 open reading frame 86 (C9orf86)
correlated with poor prognosis in non-small cell lung cancer patients.
AB - BACKGROUND: Chromosome 9 open reading frame 86 (C9orf86) is a novel subfamily of
GTPases. Previous studies have implicated C9orf86 as a potential oncogene.
METHODS: C9orf86 expression was detected in non-small cell lung cancer (NSCLC)
cell lines and human bronchial epithelial (16HBE) cell lines by RT-PCR and
western blotting. Immunohistochemistry (IHC) was used to detect 180 consecutive
NSCLC specimens and 16 normal lung tissues. The correlation between C9orf86
expression and clinicopathological parameters was evaluated. Kaplan-Meier
survival analysis and Cox hazards ratio models were used to estimate the effect
of C9orf86 expression on survival. RESULTS: C9orf86 was expressed in the
cytoplasm in 74 of 180 (41.11%) NSCLC specimens. In clinical pathology analysis,
C9orf86 expression significantly correlated with lymph node metastasis and
clinical stage significantly (P<0.05). Multivariable analysis confirmed that
C9orf86 expression increased the risk of death after adjusting for other
clinicopathological factors (P<0.01). Overall survival (OS) and disease-free
survival (DFS) were significantly prolonged in the C9orf86 negative group
compared to the C9orf86 positive group (P<0.001). Adjuvant chemotherapy prolonged
OS and DFS in resected NSCLC patients with C9orf86 negative expression (P<0.001)
but not C9orf86 positive. CONCLUSIONS: Positive expression of C9orf86 is an
independent prognostic factor for NSCLC patients, and C9orf86 may serve as a
prognostic biomarker for patients with NSCLC.
PMID- 27499932
TI - Recognition of "aggressive" behavior in "indolent" ground glass opacity and mixed
density lesions.
AB - BACKGROUND: Radiologically characteristic ground-glass opacity (GGO) represents a
special cohort of pulmonary adenocarcinomas that has been unanimously defined as
biologically inert. Lymph node metastasis, however, occurs occasionally in these
biologically "indolent" cancers. The incidence and underlying risk factors of
nodal metastasis remain unknown. METHODS: All surgically removed GGO lesions
between January 2008 and December 2014 were retrospectively reviewed from a
single treatment institution. Pathologically-confirmed adenocarcinomas with
systemic lymph node dissection or sampling were enrolled into the present study.
All the lesions were classified into three groups according to the proportion of
solid densities: group I, pure GGO; group II, 1% to 50%; and group III, 50% to
79%. Risk factor analysis of lymph node involvement was performed by multivariate
logistic regression. RESULTS: Of the 867 patients eligible for this study, 553
(63.7%) presented as pure GGOs (Group I) and 314 (36.2%) were mixed GGOs, of
which 160 (18.5%) were in group II and 154 (17.8%) in group III. Lymph node
metastasis was confirmed in 25 patients, among these 25 cases, 11 (11/160) were
group II and 14 (14/154) were group III; two of the 25 patients died from lung
cancer metastases at their postoperative 23(rd) and 36(th) month, respectively.
Statistical analysis revealed three predictors for lymph nodal metastasis: tumor
size, preoperative serum carcinoembryonic antigen level and proportion of the mix
density. CONCLUSIONS: A larger size, mixed GGOs with a higher proportion of solid
component, and elevated serum CEA level were associated with a higher preference
for nodal metastasis.
PMID- 27499933
TI - A propensity matched comparison of effects between video assisted thoracoscopic
single-port, two-port and three-port pulmonary resection on lung cancer.
AB - BACKGROUND: To summarize our experiences of single-port, two-port vs. three-port
VATS pulmonary resection for lung cancer patients. METHODS: Data of consecutive
1,553 patients who underwent video assisted thoracoscopic surgery (VATS)
pulmonary resection for lung cancer in the Department of Thoracic Surgery of
Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical
College between November 2014 and January 2016 were prospectively collected and
analyzed. A propensity-matched analysis was used to compare the short-term
outcomes of lung cancer patients who received VATS single-port, two-port and
three-port pulmonary resection. RESULTS: There were 716 males and 837 females.
The mean age was 58.90 years (range, 25-82 years) and the conversion rate was
2.7% (42/1,553) in this cohort. After propensity score matching, there were 207
patients in single-port and two-port group, and 680 patients in three-port group.
Propensity-matched analysis demonstrated that there were no significant
differences in duration of operation (129 vs. 131 min, P=0.689), intra-operative
blood loss (63 vs. 70 mL, P=0.175), number of dissected lymph nodes (12 vs. 13,
P=0.074), total hospital expense ($9,928 vs. $9,956, P=0.884) and cost of
operation ($536 vs. $535, P=0.879) between VATS single-port, two-port and
conventional three-port pulmonary resection groups. There was no significant
difference in the complication rate between two groups (5.3% vs. 4.7%, P=0.220).
However, compared with three-port group, patients who underwent single port and
two-port experienced shorter postoperative length of stay (6.24 vs. 5.61 d,
P=0.033), shorter duration of chest tube (4.92 vs. 4.25 d, P=0.008), and
decreased volume of drainage (926 vs. 791 d, P=0.003). CONCLUSIONS: The short
term outcomes between VATS single-port, two-port and conventional three-port
groups for the surgical treatment of lung cancer were comparable. However,
compared with three-port VATS pulmonary resection, single-port and two-port were
associated with shorter postoperative length of stay, shorter duration of chest
tube, and decreased volume of drainage.
PMID- 27499934
TI - Prognostic factors in non-small cell lung cancer patients who received
neoadjuvant therapy and curative resection.
AB - BACKGROUND: Lung cancer is the leading cause of cancer deaths in the world, and
more and more treatment modalities have been introduced in order to improve
patients' survival. For patients with advanced non-small cell lung cancer
(NSCLC), survival prognosis is poor and multimodality neoadjuvant therapies are
given to improve patients' survival. However, the possibility of occult
metastases may lead to discrepancy between clinical and pathologic staging and
underestimation of the disease severity. This discrepancy could be the reason for
poor survival prediction reported by previous studies which conducted their
analysis from the point of view of clinical stage. The aim of this study was to
analyze the relationship between clinico-pathologic factors and survival from the
pathologic point of view and to try to identify survival prognostic factors.
METHODS: From January 2005 to June 2011, 88 patients received neoadjuvant therapy
because of initial locally advanced disease, followed by anatomic resection and
mediastinal lymph node (LN) dissection. All their clinico-pathologic data were
collected from a retrospective review of the medical records and subjected to
further analysis. RESULTS: We found that total metastatic LN ratio (P=0.01) and
tumor size (P=0.02) were predictive factors for disease free survival (DFS). We
used these two prognostic factors to stratify all patients into four groups.
Group 4 (tumor size <=5, total metastatic LN ratio <=0.065) had the best DFS
curve, while the DFS curve progressively deteriorated across group 3 (tumor size
<=5, total metastatic LN ratio >0.065), group 2 (tumor size >5, total metastatic
LN ratio <=0.065) and group 1 (tumor size >5, total metastatic LN ratio >0.065).
However, no definitive prognostic factor could be identified in this study.
CONCLUSIONS: In conclusion, tumor size greater than 5 cm and total metastatic LN
ratio greater than 0.065 could predict the DFS of patients with advanced NSCLC
after multimodality therapies followed by surgical resection. Tumor size plays a
more important role than total metastatic LN ratio in DFS. Moreover, patients
identified with these factors need active post-operation surveillance and
additional aggressive adjuvant therapies.
PMID- 27499935
TI - Prognostic value of preoperative neutrophil-lymphocyte ratio is superior to
platelet-lymphocyte ratio for survival in patients who underwent complete
resection of thymic carcinoma.
AB - BACKGROUND: Preoperative neutrophil-lymphocyte ratio (NLR) and platelet
lymphocyte ratio (PLR) have prognostic value in patients with various operable
tumors. The aim of our study was to determine whether NLR and PLR are predictive
of survival in thymic carcinoma patients after complete resection. METHODS: A
total of seventy-nine patients who underwent complete resection of thymic
carcinoma at our hospital between January 2005 and December 2015 were
retrospectively enrolled. Differential leukocyte counts were collected before
surgery, and the relationships of NLR, PLR, and other patient clinical variables
with survival were estimated by Cox regression analysis and Kaplan-Meier survival
analysis. RESULTS: Univariate analysis found that a high level of NLR was
associated with lower disease-free survival (DFS) (HR: 3.385, 95% CI: 1.073
10.678, P=0.037) and lower overall survival (OS) (HR: 12.836, 95% CI: 1.615
101.990, P=0.016). The optimal NLR threshold of 4.1 could stratify the patients
with high risk of recurrence or metastasis (P=0.026) and death (P=0.006).
Meanwhile, the NLR value of >4.1 in those patients was associated with bigger
tumor size (P=0.035) and more advanced Masaoka stages (P=0.040) compared with NLR
<=4.1. However, the PLR and other variables were not significantly associated
with survival in thymic carcinoma patients. CONCLUSIONS: The preoperative NLR of
>4.1 was significantly associated with larger tumor size, more advanced Masaoka
stages and reduced DFS and OS, but was not an independent predictor of survival
in thymic carcinoma patients after complete resection.
PMID- 27499936
TI - Cancer-related inflammation as predicting tool for treatment outcome in locally
advanced and metastatic non-small cell lung cancer.
AB - BACKGROUND: Lung cancer is the leading cause of cancer deaths and the non-small
cell lung cancer (NSCLC) represents 80% of all cases. In most cases when
diagnosed, it is in locally advanced or metastatic stage, when platinum based
doublet chemotherapy is the established therapeutic option for majority of the
patients. Predictive factors to filter the patients who will benefit the most
from the chemotherapy are not clearly defined. Objective of this study was to
explore predictive value of pre-treatment C-reactive protein (CRP), fibrinogen
and their interaction, for the response to the frontline chemotherapy. METHODS:
In this retrospective cohort study 170 patients with locally advanced and
metastatic NSCLC were included. Relationship between baseline level of CRP and
fibrinogen and response to the frontline chemotherapy was assessed. RESULTS: We
found that pre-treatment CRP and fibrinogen values were statistically
significantly correlated. Chemotherapy and CRP, fibrinogen, and their interaction
were independently significantly associated with disease control rate at re
evaluation. There was statistically significant difference in median pre
treatment CRP level between the patients with disease control or progression at
re-evaluation, 13.8 vs. 30.0 mg/L respectively, P=0.026. By Johnson-Neyman
technique we found that in patients with initial fibrinogen value below 3.5 g/L,
CRP level was significantly associated with disease control or progression of the
disease. Above this fibrinogen value the association of CRP and disease control
was lost. CONCLUSIONS: The findings from this study support the growing evidence
of inflammation and cancer relationship, where elevated pre-treatment level of
CRP has negative predictive significance on the NSCLC frontline chemotherapy
response.
PMID- 27499937
TI - Icotinib combined whole brain radiotherapy for patients with brain metastasis
from lung adenocarcinoma harboring epidermal growth factor receptor mutation.
AB - BACKGROUND: The brain is a metastatic organ that is most prone to lung
adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis
remains very poor. In this study, we evaluated the efficacy of icotinib plus
whole brain radiation therapy (WBRT) for treating patients with brain metastasis
from epidermal growth factor receptor (EGFR)-mutated LAC. METHODS: All patients
received standard WBRT administered to the whole brain in 30 Gy in 10 daily
fractions. Each patient was also instructed to take 125 mg icotinib thrice per
day beginning from the first day of the WBRT. After completing the WBRT,
maintenance icotinib was administered until the disease progressed or intolerable
adverse effects were observed. Cranial progression-free survival (CPFS) and
overall survival (OS) times were the primary endpoints. RESULTS: A total of 43
patients were enrolled in this study. Two patients (4.7%) presented a complete
response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The
median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year
CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7%
for the patients with EGFR exon 21 L858R (P=0.027). CONCLUSIONS: The concurrent
administration of icotinib and WBRT exhibited favorable effects on the patients
with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS
following icotinib plus WBRT.
PMID- 27499938
TI - Ginsenoside Rg1 attenuates hypoxia and hypercapnia-induced vasoconstriction in
isolated rat pulmonary arterial rings by reducing the expression of p38.
AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease
characterized by increased pulmonary arteriolar resistance. Pulmonary
vasoconstriction has been proved to play a significant role in PAH. We previously
reported that Panax notoginseng saponins (PNS) might attenuate hypoxia and
hypercapnia-induced pulmonary vasoconstriction (HHPV). METHODS: In the present
study, our specific objective was to investigate the role of ginsenoside Rg1, a
major component of PNS, in this process and the possible underlying mechanism.
The second order pulmonary rings isolated from the Sprague-Dawley rats were
treated with different dosage of ginsenoside Rg1 at 8, 40, or 100 mg/L
respectively, both before and during the conditions of hypoxia and hypercapnia.
Contractile force changes of the rings were detected. Furthermore, SB203580, the
selective inhibitor for p38 activation was applied to the rings. Pulmonary
arterial smooth muscle cells (PASMCs) were cultured under hypoxic and hypercapnic
conditions, and ginsenoside Rg1 was administered to detect the changes induced by
p38. RESULTS: Under the hypoxic and hypercapnic conditions, we observed a
biphasic pulmonary artery contractile response to the second pulmonary artery
rings. It is hypothesized that the observed attenuation of vasoconstriction and
the production of vasodilation could have been induced by ginsenoside Rg1. This
effect was significantly reinforced by SB203580 (P<0.05 or P<0.01). The
expression of p38 in the PASMCs under hypoxic and hypercapnic conditions was
significantly activated (P<0.05 or P<0.01) and the observed activation was
attenuated by ginsenoside Rg1 (P<0.05 or P<0.01). CONCLUSIONS: Our findings
strongly support the significant role of ginsenoside Rg1 in the inhibition of
hypoxia and hypercapnia-induced vasoconstriction by the p38 pathway.
PMID- 27499939
TI - Implications of the pulmonary artery to ascending aortic ratio in patients with
relatively mild chronic obstructive pulmonary disease.
AB - BACKGROUND: Identifying markers for predicting the course and outcome of chronic
obstructive pulmonary disease (COPD) remains important. The relative pulmonary
artery enlargement to aorta ratio (PA-A ratio), which is measured using computed
tomography (CT), is a reported predictor for COPD exacerbation and mortality.
However, little is known about the implications of the PA-A ratio in patients
with mild COPD. METHODS: We investigated the utility of the PA-A ratio as a
biomarker in patients with relatively mild COPD. A total of 131 patients with
mild to moderate COPD [post-bronchodilator forced expiratory volume in 1 sec
(FEV1)/forced vital capacity (FVC) 61.6+/-6.4, mean post-bronchodilator FEV1
83%+/-17.8% of predicted value] were selected from a Korean COPD cohort (from
2012 until the end of 2014) and analyzed retrospectively. We determined the
correlation between the PA-A ratio and clinical parameters using a linear
regression model. RESULTS: The COPD assessment test (P=0.04), FEV1 (P=0.03), and
a history of exacerbation in the last year (P=0.03) were significant factors in
the univariate linear regression analysis. Post-bronchodilator FEV1 was most
significantly associated with the PA-A ratio in the multivariate analysis
(P=0.01). CONCLUSIONS: The PA-A ratio evaluated by CT imaging was independently
correlated with a representative pulmonary function factor (FEV1) in patients
with relatively mild COPD. The results suggest that the PA-A ratio may be an
important biomarker for clinical outcome in patients with mild COPD.
PMID- 27499940
TI - Severity of coronary artery disease and retinal microvascular signs in patients
with diagnosed versus undiagnosed diabetes: cross-sectional study.
AB - BACKGROUND: There is increasing evidence that a considerable proportion of
patients with diabetes remain undiagnosed and untreated, however, it is unclear
whether this is associated with more severe coronary artery disease (CAD) and
microvasculature changes compared with diagnosed patients. We assessed CAD extent
and severity, along with changes to the retinal microvascular structure in
participants with undiagnosed versus diagnosed type 2 diabetes. METHODS:
Participants of the Australian Heart Eye Study were stratified into participants
with previously diagnosed diabetes (n=489), undiagnosed diabetes (n=76) and no
diabetes (n=1,112). Retinal vessel caliber was measured from digital retinal
images. Extent and severity of CAD was assessed using Extent and Gensini scores
from angiography findings, respectively. RESULTS: Participants with undiagnosed
and diagnosed diabetes versus those with no diabetes (reference group) had
increased odds of being in the highest quartile of Gensini scores, multivariate
adjusted odds ratios (OR) =7.02 [95% confidence interval (CI), 2.04-24.1] and OR
=2.76 (95% CI, 1.67-4.55), respectively. Participants with undiagnosed and
diagnosed diabetes versus those with no diabetes also had increased odds of being
in the highest quartile of Extent scores, multivariate adjusted OR =7.63 (95% CI,
2.15-27.10) and OR =3.72 (95% CI, 2.22-6.27), respectively. No significant
differences were observed in retinal vessel caliber between participants with
undiagnosed versus diagnosed diabetes. CONCLUSIONS: The present study
demonstrated that participants with undiagnosed diabetes compared to those with
previously diagnosed diabetes, had a stronger likelihood of having more severe
and extensive CAD. However, retinal microvascular signs did not differ by
diabetes status.
PMID- 27499941
TI - The Aquamantys((r)) system improves haemostasis and pneumostasis in open
decortication for thoracic empyema.
AB - BACKGROUND: Decortication for thoracic empyema is associated with significant
blood loss and prolonged postoperative air leak. We sought to assess the
potential application of an irrigated-tip radiofrequency (RF) sealing device, in
an attempt to reduce this morbidity. METHODS: Data for all patients undergoing
open decortication (OD) for stage II thoracic empyema, using either conventional
approach or facilitated by use of the Aquamantys((r)) device, at a single
thoracic surgical unit between April 2010 and July 2014, were retrospectively
analysed. Unpaired t-test and Fisher's exact test were used for statistical
analysis. RESULTS: Thirty-three patients, aged 54+/-15 years (mean +/- SD), and
with a Charlson comorbidity index of 2.5+/-1.9 were included. Preoperative and
intraoperative characteristics, including surgical time, were similar in the
conventional and Aquamantys((r)) groups. Patients in the Aquamantys group were
less likely to require red cell transfusion (9/22 vs. 10/11 patients, P=0.024)
and received lower volume transfusions [0.0 (2.0) vs. 3.0 (1.6) units (median,
IQR), P<0.0001]; chest drain duration was shorter [3.0 (1.0) vs. 6.5 (6.8) days,
P=0.006], as was length of postoperative hospital stay [6.0 (8.7) vs. 10.0 (4.6)
days, P=0.031]. There was no demonstrable difference in mortality. CONCLUSIONS:
Our data indicates that the use of irrigated tip RF ablation is safe and
effective in improving pneumostasis and haemostasis in decortication for thoracic
empyema; and that this translates to morbidity and logistical benefit.
PMID- 27499942
TI - Liver failure in total artificial heart therapy.
AB - BACKGROUND: Congestive hepatopathy (CH) and acute liver failure (ALF) are common
among biventricular heart failure patients. We sought to evaluate the impact of
total artificial heart (TAH) therapy on hepatic function and associated clinical
outcomes. METHODS: A total of 31 patients received a Syncardia Total Artificial
Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic
derangements that were clinically insignificant and did not qualify as acute or
chronic liver failure, 5 patients exhibited ALF and 9 various hepatic
derangements owing to CH. Liver associated mortality and postoperative course of
liver values were prospectively documented and retrospectively analyzed. RESULTS:
Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20%
(P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal
liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a
markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a
significant deterioration. CONCLUSIONS: TAH therapy results in recovery of
hepatic function in ALF cases. Patients with CH prior to surgery form a high risk
group with increased liver associated mortality.
PMID- 27499943
TI - Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion
of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural
dissemination.
AB - BACKGROUND: This study aimed to investigate the safety and feasibility of
intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive
surgery as a part of multimodal strategy for the treatment of advanced lung
adenocarcinoma. METHODS: Medical records of advanced lung cancer patients with
pleural dissemination who underwent surgical treatment between 2003 and 2013 were
reviewed retrospectively. Enrolled patients were divided into a surgery group
comprising patients who underwent surgery only and an IPHC group, which consisted
of patients who underwent surgery combined with IPHC. RESULTS: A total of 33
patients were enrolled in this study. Twenty-three patients underwent IPHC after
surgical resection, and 10 patients underwent surgical resection only. The
complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of
which included postoperative mortality. The complication rate of the surgery
group was 40.0% (4 cases), which included one postoperative mortality. The 6
month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%,
91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0%
and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the
IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%,
33.3% and 0.0%, respectively. There were significant differences in overall
survival rates between two groups (P=0.045); however, progression-free survival
was not different between the two groups. CONCLUSIONS: IPHC combined with
cytoreductive surgery for advanced lung adenocarcinoma associated with pleural
seeding could be performed safely and feasible. It would be part of multimodality
therapy for certain category of advanced lung adenocarcinoma. However, the long
term benefits for survival is uncertain. More extensive and precisely designed
studies are warranted to further evaluate the effectiveness of IPHC.
PMID- 27499944
TI - Pure ground-glass opacity on chest computed tomography: predictive factors for
invasive adenocarcinoma.
AB - BACKGROUND: Pure ground-glass opacity (GGO) on computed tomography (CT) is
considered a diagnostic feature of noninvasive lung adenocarcinoma. However, pure
GGO can sometimes be associated with invasive adenocarcinoma (IA). The purpose of
this study was to determine the predictive factors for IA when pure GGO is
present. METHODS: Between 2011 and 2014, 83 patients with persistent pure GGO on
chest CT underwent surgical treatment for lung cancer. We compared the clinical,
surgical, and pathological characteristics of non-IA with those of IA. RESULTS: A
total of 66 patients (79.5%) were diagnosed with non-IA and 17 patients (20.5%)
were diagnosed with IA. The mean axial diameter of the GGO lesions in IA was
larger than that in non-IA (1.9 vs. 1.2 cm; P<0.001). The incidence of pleural
retraction was higher in IA than in non-IA (76.5% vs. 15.2%; P<0.001).
Multivariate logistic regression analysis identified GGO lesion size and the
presence of pleural retraction as significant predictive factors for IA.
CONCLUSIONS: Both preoperative GGO lesion size on CT and the computed-tomography
or operative finding of pleural retraction are predictive factors for IA. In
patients with these findings, curative lobectomy is preferable to limited
resection.
PMID- 27499945
TI - Clinical outcomes of infrarenal abdominal aortic aneurysms that underwent
endovascular repair in a district general hospital.
AB - BACKGROUND: The purpose of this study was to compare the outcomes of elective
endovascular abdominal aortic aneurysm repair (EVAR) and ruptured abdominal
aortic aneurysm (rAAA) in patients at a district general hospital. METHODS: A
retrospective clinical study was conducted using data on 16 patients with
elective abdominal aortic aneurysm (AAA) and nine patients with consecutive rAAA
treated with EVAR from January 2010 to December 2014 in a district general
hospital in Taiwan. RESULTS: The preoperative characteristics of the two groups
are listed. Thirty-six percent (9/25) of the patients were referred from other
hospitals that did not offer surgical services. The percentage of patients with
rAAA that were transferred from other hospitals was 55.5% (5/9). The stay
durations in the intensive care unit for elective EVAR cases were shorter than
those for emergent EVAR (1.75+/-1 d elective vs. 10+/-13.37 d emergent; P<0.019).
The hospitalization days (11.06+/-4.07 d elective vs. 21.89+/-18.36 d emergent;
P<0.031), operative time (183.63+/-57.24 min elective vs. 227.11+/-59.92 min
emergent; P<0.009), and blood loss volumes (115.63+/-80.41 mL elective vs.
422.22+/-276.26 mL emergent; P<0.005) are shown; statistics for use of Perclose
ProGlide((r)) (7 cases elective vs. 0 case emergent; P<0.024) are compared. The
overall 30-d mortality rate was 11.11% (1/9). CONCLUSIONS: The results confirm
that EVAR surgery can be safely performed in a district general hospital with an
integrated health care system. Using Perclose ProGlide((r)) for selected cases
may reduce blood loss and operative time.
PMID- 27499946
TI - Conservative management of empyema-complicated post-lobectomy bronchopleural
fistulas: experience of consecutive 13 cases in 9 years.
AB - BACKGROUND: Bronchopleural fistula (BPF) is an infrequent but life-threatening
complication after lung surgery. Tentative closure of the fistula and irrigation
have been the conventional treatments, but are also surgically challenging and
associated with a considerable failure rate. This study reports on a conservative
practice of this difficult issue, in aim to examine its outcomes. METHOD: All
enrolled cases were handled consecutively from September 2006 to June 2015. The
empyema was first properly drained till disseminated pneumonia controlled. After
conducting lavage, tube drainage was gradually transited to postural drainage.
During the follow-up, information on tube removal, fistula healing, and survival
were recorded. RESULTS: Thirteen cases were enrolled, including 9 rights and 4
lefts. The primary diseases were lung cancer [10], lung abscess [1], organizing
pneumonia [1], and aspergillosis [1]. Early fistula (<=30 days postoperatively)
occurred in 8 cases and late fistula (>30 days postoperatively) in 5 cases. Two
patients underwent debridement to ascertain complete drainage. Chest tubes
retained from 7 to 114 days (mean 40.54+/-30.49 days) before removal. At follow
up, we observed gradually narrowing-down of all residual cavities, and symptoms
of fistula and empyema eventually disappeared in all patients. No complication or
death occurred during the follow-up. CONCLUSIONS: Conservative management by a
combination of tube and postural drainage provides an effective and safe
treatment for empyema-complicated post-lobectomy BPFs.
PMID- 27499947
TI - Clinicopathological and prognostic significance of Oct-4 expression in patients
with non-small cell lung cancer: a systematic review and meta-analysis.
AB - BACKGROUND: Octamer-binding transcription factor 4 (Oct-4) has been identified to
participate in the tumorigenicity and malignancy of non-small cell lung cancer
(NSCLC). However, its definite prognostic roles in NSCLC still remain a debate.
Therefore, we conducted this meta-analysis to evaluate the prognostic value of
Oct-4 expression in NSCLC and its relationship to some major clinicopathological
characteristics. METHODS: A comprehensive literature retrieval was performed in
PubMed, EMBASE and the Web of Science to identify the full-text articles that met
our eligibility criteria. Odds ratio (OR) with 95% confidence interval (CI)
severed as the summarized statistics for clinicopathological assessments, and
hazard ratio (HR) with 95% CI served as the summarized statistics for prognostic
assessments. Q-test and I(2)-statistic were used to evaluate the level of
heterogeneity. Potential publication bias was detected by both Begg's test and
Egger's test. RESULTS: There were 16 retried articles with 1,363 NSCLC cases
included into this meta-analysis. Oct-4 expression was found to be significantly
associated with the unfavorable outcomes for differentiation degree (OR: 3.065;
95% CI: 1.568-5.957; P=0.001), TNM stage (OR: 3.695; 95% CI: 2.252-6.063;
P<0.001) and lymphatic metastasis (OR: 2.372; 95% CI: 1.504-3.742; P<0.001), but
not associated with the histological subtypes, gender, age and smoking status.
Oct-4 expression was also significantly associated with the poor prognosis of
NSCLC (HR: 3.030; 95% CI: 2.283-4.021; P<0.001). The prognostic roles of Oct-4
expression in NSCLC still remained statistically reliable in the subgroups
stratified by statistical analysis, patients' origins, positively-stained sites
and histological subtypes. CONCLUSIONS: Our meta-analysis indicates that Oct-4
can serve as a strong biomarker predicting the poor clinicopathological and
prognostic characteristics of NSCLC. More high-quality studies based on a large
sample size will be very helpful to further validate and modify our findings in
the future.
PMID- 27499948
TI - Long-term performance of the second-generation cobalt-chromium sirolimus-eluting
stents in real-world clinical practice: 3-year clinical outcomes from the
prospective multicenter FOCUS registry.
AB - BACKGROUND: The short- and mid-term outcomes of the second-generation cobalt
chromium sirolimus-eluting stent (CoCr-SES) in real-world patients had been
reported previously, but the long-term performance remained unclear. The
objective of this analysis was to evaluate the long-term safety and efficacy of
the second-generation CoCr-SES from the FOCUS registry. METHODS: The FOCUS
registry (ClinicalTrials.gov Identifier: NCT00868829) enrolled all-comers
eligible to receive Firebird-2 CoCr-SES. Follow-up was continued to 3 years to
evaluate long-term safety and effectiveness of the second-generation CoCr-SES in
real-world practice. Results of the extended-use group and standard-use group are
compared to explore performance of CoCr-SES in more severe patients with more
complex lesions. RESULTS: The rate of 3-year MACE was 7.37%, consisting of 84
cases (1.78%) of cardiac death, 166 cases (3.52%) of MI and 98 cases (2.08%) of
TVR. ARC definite/probable stent thrombosis happened in 34 (0.72%) patients, only
3 new cases (<0.1%) of very late stent thrombosis was reported in the third year.
Meanwhile, the difference of MACE (7.77% vs. 6.06%; P=0.058), TLF (4.71% vs.
3.49%; P=0.085) and ARC definite/probable stent thrombosis (0.83% vs. 0.37%;
P=0.116) between extended-use group and standard-use group showed no
significance. CONCLUSIONS: The second-generation CoCr-SES was associated with
continued low rates of 3-year MACE, TLF and stent thrombosis in a broad spectrum
of patients.
PMID- 27499949
TI - The relationship between preoperative serum cortisol level and the stability of
plaque in carotid artery stenosis patients undergoing carotid endarterectomy.
AB - BACKGROUND: Stability of plaque has been implicated as risk factor for stroke.
Serum cortisol regulates lipoprotein metabolism and immune response, contributing
to plaque stability in atherosclerosis. However, the relationship between serum
cortisol and stability of carotid plaque has not been well characterized. We
conducted a serology analysis to identify the relationship between serum cortisol
and carotid plaque stability. METHODS: Between May 2013 to October 2015, 73
patients with carotid stenosis patients undergoing carotid endarterectomy (CEA)
were enrolled in our study. Serum cortisol was analyzed at 8:00 AM in the morning
before surgery via liquid chromatography tandem mass spectrometry. According to
the classification made by the American Heart Association, hematoxylin-and-eosin
staining was performed to divide these patients into either a stable or unstable
group, according to the morphology of fibrous cap, lipid core and intima layer. A
curve fitting method was used to identify the relationship between preoperative
serum cortisol and stability of carotid plaque. Univariate and multivariate
logistic regression analysis were used to identify carotid plaque stability
associated serum cortisol. RESULTS: Curve fitting's result represents a U-shape
characteristic. A total of 314.92 and 395.23 nmol/L were considered as the cut
point for preoperative serum cortisol when trisected the patients. When adjusted
for degree of stenosis, hyperlipemia, smoking and low-density lipoprotein (LDL),
univariate and multivariate logistic regression analysis' results demonstrated
that preoperative serum cortisol can significantly affect carotid plaque
stability. The odds ratio values in multivariate logistic regression analysis for
C reactive protein (CRP), white blood cell (WBC), interleukin-6 (IL-6) and
preoperative serum cortisol level were 7.67 and 20.86 respectively. CONCLUSIONS:
Preoperative serum cortisol was associated with stability of carotid plaque in
patients undergoing CEA. Low or high levels of preoperative serum cortisol might
be an adverse factor for carotid plaque stability.
PMID- 27499950
TI - A 20-year study on treating childhood infective endocarditis with valve
replacement in a single cardiac center in China.
AB - BACKGROUND: Children with infective endocarditis (IE) have to undergo valve
replacement instead of valve repair in China due to severe valve damage. The
present study is to review our experience on surgical treatment of children with
IE in reference to the incidence, pathologic status, diagnosis, surgical
strategies and outcomes. METHODS: We reviewed 35 patients with a mean age of
13.7+/-2.2 years who were underwent valve replacement surgery for IE during the
period from January 1993 to December 2013. Preoperative transthoracic
echocardiographic (TTE) evaluation and transesophageal echocardiography during
operation were performed in all patients. All the children underwent chart review
and retrospective risk-hazard analysis. RESULTS: Among the patients surveyed
congenital cardiac lesions were present in 15 (42.8%), rheumatic heart valve
disease in 2 (5.7%) and previous heart surgery in 2 (5.7%). The median stay of
intensive care unit was 6 days. Intraoperative findings showed that the
endocarditis involved mostly the mitral and aortic valves (88.5%). Triple or
quadruple valve involvement was found in one patient each. Ten-year freedom from
IE-related death and re-intervention was 94.2% and 91.6%, respectively.
CONCLUSIONS: Children undergoing surgery for IE frequently have advanced disease
with embolic complications. Although valve replacement is not the primary option
for pediatric IE, the rate of 5-year survival and freedom from re-operation was
optimal prognostically. Pediatric physicians should pay attention to the common
clinical features of IE so that the native valve is preserved well.
PMID- 27499951
TI - A systematic review and meta-analysis-does chronic obstructive pulmonary disease
predispose to bronchopleural fistula formation in patients undergoing lung cancer
surgery?
AB - BACKGROUND: we conducted this systematic meta-analysis to determine the
association between chronic obstructive pulmonary disease (COPD) and risk of
bronchopleural fistula (BPF) in patients undergoing lung cancer surgery. METHODS:
Literature retrieval was performed in PubMed, Embase and the Web of Science to
identify the full-text articles that met our eligibility criteria. Odds ratio
(OR) with 95% confidence interval (CI) served as the summarized statistics. Q
test and I(2)-statistic were used to evaluate the level of heterogeneity.
Sensitivity analysis was performed to further examine the stability of pooled OR.
Publication bias was detected by both Begg's test and Egger's test. RESULTS:
Eight retrospective observational studies were included into this meta-analysis.
The overall summarized OR was 2.03 (95% CI: 1.44-2.86; P<0.001), revealing that
COPD was significantly associated with the risk of BPF after lung cancer surgery.
In subgroup analysis, the relationship between COPD and BPF occurrence remained
statistically prominent in the subgroups stratified by statistical analysis
(univariate analysis, OR: 1.91; 95% CI: 1.35-2.69; P<0.001; multivariate
analysis, OR: 3.18; 95% CI: 1.95-5.19; P<0.001), operative modes (pneumonectomy,
OR: 2.11; 95% CI: 1.15-3.87; P=0.016) and in non-Asian populations (OR: 2.36; 95%
CI: 1.18-4.73; P=0.016). No significant impact of COPD on BPF risk was observed
in Asian patients (OR: 1.48; 95% CI: 0.85-2.57; P=0.16). No significant
heterogeneity or publication bias was discovered across the included studies.
CONCLUSIONS: Our meta-analysis indicates that COPD can significantly predispose
to BPF formation in patients undergoing lung cancer surgery. Because some
limitations still exist in this meta-analysis, our findings should be further
verified and modified in the future.
PMID- 27499952
TI - Mutations and expression of the NFE2L2/KEAP1/CUL3 pathway in Chinese patients
with lung squamous cell carcinoma.
AB - BACKGROUND: Recent studies have reported an abnormally high alteration rate in
the nuclear factor erythroid 2-like 2 (NFE2L2)/kelch-like ECH-associated protein
1 (KEAP1)/cullin 3 (CUL3) pathway. But the status of this pathway in Chinese
patients with lung squamous cell carcinoma (SqCC) has not been thoroughly
studied, and there are many uncertainties regarding the expression of pathway
intermediates. METHODS: cDNA sequencing and TaqMan qRT-PCR were carried out in
paired cancer and adjacent normal samples obtained from 100 Chinese patients with
lung SqCC. Immunohistochemical staining was performed in 50 other paraffin
embedded specimens. RESULTS: We detected 47 mutations in 36 patients (36%), and
143 single nucleotide polymorphism (SNP) in 59 patients (59%), of which 41
mutations and 31 SNPs resulted in amino acid (AA) and possibly functional
changes. By combining qRT-PCR and immunohistochemistry staining, we confirmed
that the expression of NFE2L2 and KEAP1 were highly increased, while the
expression of CUL3 was not significantly changed in lung SqCC samples from
Chinese patients. CONCLUSIONS: Considering the frequent mutations and abnormal
expression, the NFE2L2/KEAP1/CUL3 pathway may play an important role in the
therapy of Chinese patients with lung SqCC.
PMID- 27499953
TI - Role of plasma MicroRNAs in the early diagnosis of non-small-cell lung cancers: a
case-control study.
AB - BACKGROUND: Lung cancer is a leading cause of cancer death worldwide. Early
diagnosis is essential for improvements of prognosis and survival of the
patients. Altered expressions in many cancer types including lung cancer and
stable existence in plasma make microRNAs (miRNAs) a group of potentially useful
biomarkers for clinical assessments of patients with lung cancer. In this study,
we evaluate the potential values of miRNAs as plasma biomarkers for early
diagnosis in non-small-cell lung cancers (NSCLC) by comparing with other typical
plasma biomarkers. METHODS: We analyzed the clinical and laboratory
characteristics of 59 early-staged NSCLC (I-IIIA) patients and non-cancer
controls by 1:1 matching age and gender from January 2012 to February 2014 in
Xuanwu Hospital, Beijing, China. Peripheral blood samples from patients and
controls before surgery were collected, and plasma was separated. Expression of
ten miRNAs in the plasma of the patients and controls was detected by
quantitative real-time polymerase chain reaction. Other typical markers, such as
SCC, CEA, and CYFRA21-1 in plasma were also detected. The early diagnostic
ability of miRNAs and other markers were evaluated by receiver-operating
characteristic (ROC) curve analysis. The sensitivity, specificity, and area under
the curve were calculated for the cut-off value. RESULTS: Plasma CYFRA21-1, miRNA
486 and miRNA-210 levels were significantly different in patients with NSCLC than
those in controls (CYFRA21-1: 8.896+/-7.681 vs. 5.892+/-6.028, P=0.020; miR-486:
2.778+/-0.778 vs. 1.746+/-0.892, P<0.001; miR-210: 4.836+/-3.374 vs. 2.829+/
2.503, P<0.001). Area under ROC curve of CYFRA21-1, miR-486 and miR-210 were
0.624 (sensitivity: 0.576, specificity: 0.797), 0.848 (sensitivity: 0.831,
specificity: 0.780) and 0.751 (sensitivity: 0.746, specificity: 0.746),
respectively. The optimal cut-off value of CYFRA21-1, miRNA-486 and miRNA-210
were 6.595, 1.988 and 3.341, respectively to discriminate patients from controls.
Plasma markers combined diagnosis ability had the highest sensitivity: 0.983, but
the specificity was low. miR-486, miR-210 and CYFRA21-1 combined diagnosis
ability was the highest, and the AUC was 0.924 (sensitivity: 0.847; specificity:
0.728). CONCLUSIONS: The results suggest that miRNA-486 and miR-210 could be
potential blood-based biomarkers for early diagnosis of NSCLC. miRNAs and other
lab indexes may be combined to early diagnose NSCLC, which showed better ability
of screening patients.
PMID- 27499954
TI - Mediastinal transposition of the omentum reduces infection severity and pharmacy
cost for patients undergoing esophagectomy.
AB - BACKGROUND: The greater omentum has been found to be immunologically competent in
protecting abdominal organs from inflammation. Anastomotic omentoplasty has been
used and proven effective in preventing anastomotic leaks after an esophagectomy.
However, pulmonary complications are still a substantial problem after an
esophagectomy. This study investigated the benefits of mediastinal transposition
of the omentum, a modification of the conventional omental wrapping technique, in
controlling overall postoperative intrathoracic complications. METHODS: From
January 2010 to March 2015, 208 consecutive patients receiving an open Ivor-Lewis
esophagectomy at our institution were retrospectively reviewed. One hundred
twenty-one patients with omentum mediastinal transposition were assigned to the
transposition group and 87 patients without omental transposition were placed in
the non-transposition group. The patients' demographics, postoperative short-term
outcomes, and in-hospital cost were documented and analyzed. RESULTS: Mediastinal
transposition of the omentum led to a shorter postoperative hospital stay (14 vs.
16 d, P=0.038) and a lower intrathoracic infection rate (30.6% vs. 48.3%,
P=0.009). Intrathoracic infection was milder in the transposition group
(P=0.005), though a non-significant was found in overall complications (P=0.071).
The multivariate logistic regression analyses identified omentum mediastinal
transposition (P=0.007, OR=0.415) as an independent protective factor for
postoperative intrathoracic infection. The total in-hospital cost was comparable
in both groups (P>0.05), whereas the pharmacy cost was lower in the transposition
group than in the non-transposition group (Y21,668 vs. Y27,012, P=0.010).
CONCLUSIONS: Mediastinal transposition of the omentum decreases the rate and
severity of postoperative intrathoracic infection following an open Ivor-Lewis
esophagectomy. This result in decreased pharmacy costs, rather than resulting in
an increased economic burden sustained by surgical patients.
PMID- 27499955
TI - Evaluation of a disease management program for COPD using propensity matched
control group.
AB - BACKGROUND: Disease management programs (DMPs) have proliferated recently as a
means of improving the quality and efficiency of care for patients with chronic
illness. These programs include education about disease, optimization of evidence
based medications, information and support from case managers, and institution of
self-management principles. Chronic obstructive pulmonary disease (COPD) is a
major cause of morbidity and mortality in Singapore and worldwide. DMP aims to
reduce mortality, hospitalizations, and average length of stay in such patients.
This study assesses the outcomes of the DMP, comparing the propensity score
matched DMP patients with controls. METHODS: DMP patients were compared with the
controls, who were COPD patients fulfilling the DMP's inclusion criteria but not
included in the program. Control patients were identified from Operations Data
Store (ODS) database. The outcomes of interest were average length of stay,
number of days admitted to hospital per 100 person days, readmission, and
mortality rates per person year. The risk of death and readmission was estimated
using Cox, and competing risk regression respectively. Propensity score was
estimated to identify the predictors of DMP enrolment. DMP patients and controls
were matched on their propensity score. RESULTS: There were 170 matched DMP
patients and control patients having 287 and 207 hospitalizations respectively.
Program patient had lower mortality than the controls (0.12 vs. 0.27 per person
year); cumulative 1-year survival was 91% among program patient and 76% among the
control patients. Readmission, and hospital days per 100 person-days was higher
for the program patients (0.36 vs. 0.17 per person year), and (2.19 vs. 1.88 per
person year) respectively. CONCLUSIONS: Participation in "DMP" was associated
with lower all-cause mortality when compared to the controls. This survival gain
in the program patients was paradoxically associated with an increase in
readmission rate and total hospital days.
PMID- 27499956
TI - Evaluation of the 7(th) edition of the UICC-AJCC tumor, node, metastasis
classification for esophageal cancer in a Chinese cohort.
AB - BACKGROUND: To assess and evaluate the prognostic value of the 7(th) edition of
the Union for International Cancer Control-American Joint Committee on Cancer
(UICC-AJCC) tumor, node, metastasis (TNM) staging system for Chinese patients
with esophageal cancer in comparison with the 6(th) edition. METHODS: A
retrospective review was performed on 766 consecutive esophageal cancer patients
treated with esophagectomy between 2008 and 2012. Patients were staged according
to the 6(th) and 7(th) editions for esophageal cancer respectively. Survival was
calculated by the Kaplan-Meier method, and multivariate analysis was performed
using Cox regression model. RESULTS: Overall 3-year survival rate was 59.5%.
There were significant differences in 3-year survival rates among T stages both
according to the 6(th) edition and the 7(th) edition (P<0.001). According to the
7(th) edition, the 3-year survival rates of N0 (75.4%), N1 (65.2%), N2 (39.7%)
and N3 (27.3%) patients were significant differences (P<0.001). Kaplan-Meier
curve revealed a good discriminatory ability from stage I to IV, except for stage
IB, IIA and IIB in the 7(th) edition staging system. Based on the 7(th) edition,
the degree of differentiation, tumor length and tumor location were not
independent prognostic factors on multivariate analysis. The multivariate
analyses suggested that pT-, pN-, pTNM-category were all the independent
prognostic factors based on the 6(th) and 7(th) edition staging system.
CONCLUSIONS: The 7(th) edition of AJCC TNM staging system of esophageal cancer
should discriminate pT2-3N0M0 (stage IB, IIA and IIB) better when considering the
esophageal squamous cell cancer patients. Therefore, to improve and optimize the
AJCC TNM classification for Chinese patients with esophageal cancer, more
considerations about the value of tumor grade and tumor location in pT2-3N0M0
esophageal squamous cell cancer should be taken in the next new TNM staging
system.
PMID- 27499957
TI - A potential role for VEGF in the diagnostic approach of pleural effusions.
AB - BACKGROUND: Vascular endothelial growth factor (VEGF) may play a role in pleural
fluid formation, as it represents a potent inducer of capillary permeability. We
aimed to investigate the diagnostic utility of VEGF levels in pleural fluid and
serum in patients with pleural effusions with initially negative diagnostic work
up. METHODS: Seventy-one patients with exudative lymphocytic pleural effusions
undiagnosed after initial diagnostic work up were enrolled in this prospective
study and their clinical course was followed up to 24 months. VEGF levels were
measured in serum and pleural fluid by using immunoenzymometric assay. RESULTS:
During the follow up period, in 43 patients the pleural effusion was eventually
attributed to malignancy while in the rest 28 patients it was due to non
malignant causes (benign and unknown origin). Patients with malignancy had
significantly higher VEGF levels in pleural fluid compared to patients with non
malignant effusions (1,506 vs. 588 pg/dL, P=0.0001), while no statistically
significant difference was found in the VEGF serum levels between the two groups.
CONCLUSIONS: Pleural VEGF levels may be helpful in identifying malignant pleural
effusion (MPE) in patients with negative diagnostic work up at the initial
assessment and help in selecting patients for more invasive procedures.
PMID- 27499958
TI - Diagnostic performance of coronary computed tomography angiography versus
exercise electrocardiography for coronary artery disease: a systematic review and
meta-analysis.
AB - BACKGROUND: Both coronary computed tomography angiography (CCTA) and exercise
electrocardiography (ExECG) are non-invasive testing methods for the evaluation
of coronary artery disease (CAD). However, there was controversy on the
diagnostic performance of these methods due to the limited data in each single
study. Therefore, we performed a meta-analysis to address these issues. METHODS:
We searched PubMed and Embase databases up to May 22, 2015. Two authors
identified eligible studies, extracted data and accessed quality. Pooled
estimation of sensitivity, specificity, positive likelihood ratio (PLR), negative
likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver-operating
characteristic curve (SROC) and the area under curve (AUC) of CCTA and ExECG for
the diagnosis of CAD were calculated using Stata, Meta-Disc and Review Manager
statistical software. RESULTS: Seven articles were included. Pooled sensitivity
of CCTA and ExECG were 0.98 [95% confidence intervals (CIs): 0.95-0.99] and 0.66
(95% CIs: 0.59-0.72); pooled specificity of CCTA and ExECG were 0.84 (95% CIs:
0.81-0.87) and 0.75 (95% CIs: 0.71-0.79); pooled DOR of CCTA and ExECG were
110.24 (95% CIs: 35.07-346.55) and 6.28 (95% CIs: 2.06-19.13); and AUC of CCTA
and ExECG were 0.9950+/-0.0046 and 0.7727+/-0.0638, respectively. There is no
heterogeneity caused by threshold effect in CCTA or ExECG analysis. The Deeks'
test showed no potential publication bias (P=0.17). CONCLUSIONS: CCTA has better
diagnostic performance than ExECG in the evaluation of CAD, which can provide a
better solution for the clinical problem of the diagnosis for CAD.
PMID- 27499959
TI - Benefits of using omental pedicle flap over muscle flap for closure of open
window thoracotomy.
AB - BACKGROUND: Open window thoracotomy (OWT) as well as its closure are challenging.
Transposition of omental pedicle and muscle flaps is often performed for OWT
closure; however, the better technique among the two is unknown. The purpose of
this series was to evaluate the outcomes of using both omental pedicle and muscle
flaps for the aforementioned closure. METHODS: This was an observational
retrospective cohort study on 27 consecutive patients who underwent OWT closure
at a single institution between January 2005 and December 2014. The operation was
performed using either omental pedicle or muscle flap with thoracoplasty. We
compared both techniques in terms of the patient background [sex, age, body mass
index (BMI) and C-reactive protein (CRP) before OWT and serum albumin levels
before OWT closure], presence of methicillin-resistant Staphylococcus aureus
(MRSA) infection, rate of bronchopleural fistula (BPF), duration of OWT,
recurrence of local infection, morbidity, duration of indwelling drainage after
operation, success, mortality and postoperative hospital stay. RESULTS: There
were 9 (33.3%) omental pedicle flap procedures and 18 (66.7%) muscle flap
procedures. The rate of local recurrence after closure of OWT was significantly
higher with muscle flap than with omental pedicle flap (0% vs. 50.0%, P=0.012).
The median duration of postoperative hospital stay was significantly shorter with
omental pedicle flap than that with muscle flap (16.0 vs. 41.5 days, P=0.037).
Mortality was observed in 2 patients (11.2%) in the muscle flap group and no
patient in the omental pedicle flap group. Success rate was similar between the
two groups (100% for omental pedicle flap vs. 83.3% for muscle flap).
CONCLUSIONS: Omental pedicle flap was superior to muscle flap in terms of
reducing local recurrence and shortening postoperative hospital stay. However,
mortality, morbidity and success rates were not affected by the choice of flap.
PMID- 27499960
TI - Association between NADPH oxidase (NOX) and lung cancer: a systematic review and
meta-analysis.
AB - BACKGROUND: Lung cancer is a leading cause of death worldwide. Considerable
studies have reported that NADPH oxidase (NOX) expression or activity may play an
important role in the tumorigenesis of lung cancer. However, the results are
inconsistent. Thus, a systematic review and meta-analysis were conducted in this
study. METHODS: A systematic search of electronic databases was performed.
Statistical analysis was performed using the Comprehensive Meta-Analysis software
(Version 3). The pooled Hedges's g with 95% confidence intervals (95% CIs) or
rate ratio with 95% CIs was adopted to assess the effect size. Fixed or random
effect model was separately used based on the heterogeneity between the studies.
RESULTS: A total of ten eligible studies were included in the current systematic
review and overall meta-analysis showed that NOX/DUOX activity and mRNA were
significantly in favor of lung cancer (Hedges's g =1.216, P=0.034). Suppression
of NOX function by pharmacologic inhibitor or expression by siRNA resulted in
significant inhibition of lung cancer cell invasion and migration in in vitro
experiments (Hedges's g =2.422, P<0.001) and lung cancer formation in vivo
studies (rate ratio =0.366, P=0.002). CONCLUSIONS: Findings of this systematic
review indicate that NOX activity and expression is associated with tumorigenesis
of lung cancer and inhibition of NOX function or mRNA expression significantly
blocks lung cancer formation and invasion. Suppressing NOX up-regulation or
interfering NOX function in tumor microenvironment may be one important approach
to prevent oxidative-stress-related carcinogenesis in the lung.
PMID- 27499961
TI - Transition to routine use of venoarterial extracorporeal oxygenation during lung
transplantation could improve early outcomes.
AB - BACKGROUND: The study objective was to compare the outcomes of intraoperative
routine use of venoarterial (VA) extracorporeal membrane oxygenation (ECMO)
versus selective use of cardiopulmonary bypass (CPB). METHODS: Between January
2010 and February 2013, 41 lung transplantations (LTx) were performed, and CPB
was used as a primary cardiopulmonary support modality by selective basis (group
A). Between March 2013 and December 2014, 41 LTx were performed, and ECMO was
used routinely (group B). The two groups were compared retrospectively. RESULTS:
The operative time was significantly longer in group A (group A, 458 min; group
B, 420 min; P=0.041). Postoperatively, patients in group B had less fresh frozen
plasma (FFP) transfusion (P=0.030). Complications were not different between the
two groups. The 30- and 90-day survival rates were better in group B (30-day
survival: group A, 75.6%; group B, 95.1%, P=0.012; 90-day survival: group A,
68.3%; group B, 87.8%, P=0.033). The 1-year survival showed better trends in
group B, but it was not significant. Forced vital capacity (FVC) at 1, 3, and 6
months after LTx was better in group B than in group A (1 month: group A, 43.8%;
group B, 52.9%, P=0.043; 3 months: group A, 45.5%; group B, 59.0%, P=0.005; 6
months: group A, 51.5%; group B, 65.2%, P=0.020). Forced expiratory volume in 1
second (FEV1) at 3 months after LTx was better in patients in group B than that
in patient in group A (group A, 53.3%; group B, 67.5%, P=0.017). CONCLUSIONS:
Routine use of ECMO during LTx could improve early outcome and postoperative lung
function without increased extracorporeal-related complication such as vascular
and neurologic complications.
PMID- 27499962
TI - Factors influencing development and mortality of acute respiratory failure in
hospitalized patient with active pulmonary tuberculosis: a 10-year retrospective
review.
AB - BACKGROUND: Pulmonary tuberculosis with acute respiratory failure is fatal and is
a burden in the intensive care units and leads to mortality. This retrospective
study identifies the factors influencing the development of pulmonary
tuberculosis requiring mechanical ventilation (TBMV) and mortality in the
hospitalized patients with pulmonary tuberculosis. METHODS: The medical records
of hospitalized adult patients with pulmonary tuberculosis were retrospectively
reviewed. Demographic data, clinical presentations, radiographic findings,
biochemical tests, and clinical outcomes were collected. Data were compared by
Student's t-test and Chi-square test between groups. Select variables that were
statistically significant with P values <0.1 were introduced into a forward,
stepwise, logistic regression model. Odds ratios (ORs) and their 95% confidence
intervals (CIs) identified the independent influencing factors in the development
of TBMV and mortality. RESULTS: Of 268 enrolled patients, 185 (69.0%) were male.
The patients were equally divided between the TBMV and non-TBMV groups. The
shorter duration of illness (OR, 0.99; 95% CI, 0.98-0.99), underlying disease of
AIDS (OR, 14.55; 95% CI, 1.71-123.91), presentation of fever (OR, 2.11; 95% CI,
1.20-3.71) and dyspnea (OR, 3.51; 95% CI, 2.02-6.11), large amount of acid fast
bacilli on sputum smear (OR, 3.76; 95% CI, 1.90-7.47), lower serum albumin level
(OR, 0.39; 95% CI, 0.26-0.59), and delayed initiation of anti-tuberculosis agents
(OR, 1.06; 95% CI, 1.00-1.12) were independent factors to develop TBMV. Male
gender (OR, 2.16; 95% CI, 1.01-4.61), consolidation pattern on chest X-ray (OR,
2.41; 95% CI, 1.17-4.98), and lower serum albumin (OR, 0.39; 95% CI, 0.21-0.71)
were correlated to mortality. CONCLUSIONS: The incidence and mortality rate of
TBMV patients were high. Acute tuberculous pneumonia, underlying disease of AIDS,
amount of acid fast bacilli, and delayed administration of anti-tuberculosis
agents were independent risk factors to develop TBMV. Male gender, consolidation
on chest X-ray, and low serum albumin were significantly related to mortality.
PMID- 27499963
TI - The diagnostic utility and tendency of the soluble receptor for advanced
glycation end products (sRAGE) in exudative pleural effusion.
AB - BACKGROUND: The soluble receptor for advanced glycation end products (sRAGE) may
have an inflammatory or homeostatic function in lung tissue. The aim of this
study was to assess the usefulness of sRAGE as a diagnostic marker for exudative
pleural effusions, which are common manifestations of a variety of diseases.
METHODS: Patients with an undiagnosed pleural effusion were prospectively
enrolled between January 2013 and January 2015. Samples of blood and pleural
fluid were centrifuged and the supernatant stored at -70 degrees C. The levels
of sRAGE in serum and pleural fluid were determined using a commercially
available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: In total 47
patients, 21 patients were diagnosed with a tuberculous effusion, and the groups
diagnosed with parapneumonic or malignant effusions comprised 13 patients each.
The serum sRAGE levels for tuberculosis were significantly elevated [median,
1,291 pg/mL; interquartile range (IQR), 948-1,711 pg/mL] when compared with those
for both pneumonia (median, 794 pg/mL; IQR, 700-1,255 pg/mL) and lung cancer
(median, 886 pg/mL; IQR, 722-1,285 pg/mL) (P=0.029). The pleural sRAGE levels for
pneumonia (median, 1,763 pg/mL; IQR, 1,262-4,431 pg/mL) were lower than those for
both tuberculosis (median, 5,081 pg/mL; IQR, 3,300-6,004 pg/mL) and lung cancer
(median, 4,936 pg/mL; IQR, 3,282-7,018 pg/mL) (P=0.009) The receiver operating
characteristic (ROC) curve analysis selected 896 pg/mL as the best cutoff value
in the sRAGE serum level for tuberculosis [sensitivity, 86%; specificity 58%;
area under the curve (AUC) =0.727, P=0.008]. For the pleural effusion sRAGE
level, the ROC curve analysis selected 2,231 pg/mL as the best cutoff value for
pneumonia (sensitivity, 91%; specificity, 62%, AUC =0.792, P=0.002). CONCLUSIONS:
Among patients with exudative effusion, pleural and serum sRAGE measurements may
be useful supportive diagnostic tools in the evaluation of ambiguous pleural
effusion. Furthermore, the behavior of sRAGE in the serum and pleural fluid of
various pulmonary diseases suggests that sRAGE may be linked to the chronic
process of lung damage and inflammation rather than acute bacterial infection.
PMID- 27499964
TI - Preoperative evaluation of stage T3, central-type non-small cell lung cancer with
double sleeve lobectomy under complete video-assisted thoracoscopic surgery using
spiral computed tomography post-processing techniques.
AB - BACKGROUND: To investigate the estimated value of spiral computed tomography (CT)
post-processing techniques in preoperative stage T3, central-type non-small cell
lung cancer (NSCLC) with double sleeve lobectomy under complete video-assisted
thoracoscopic surgery (c-VATS). METHODS: Preoperative clinical date and CT
reconstructed data of 10 patients who underwent double sleeve lobectomy with
upper lobe stage T3, central-type NSCLC were retrospectively analysed and
compared to surgical pathological results and cross-sectional CT data. The
diagnostic criterions of tumour invasion of pulmonary artery and bronchus were
divided into five grades, which included estimation of upper lobe pulmonary
arteries and bronchi (40 branches, respectively). RESULTS: The sensitivity,
specificity, positive predictive value, negative predictive value, and diagnostic
accuracy of cross-sectional CT images of pulmonary artery tumour invasion were
78.57%, 58.33%, 81.48%, 53.85%, and 72.50%, respectively, while the respective
values for CT reconstructed images were 93.55%, 87.50%, 96.67%, 70.00%, and
90.00%, showing statistical significance (chi(2)=4.021, P=0.045). Similarly, the
evaluate, the sensitivity, specificity, positive predictive value, negative
predictive value, and diagnostic accuracy of cross-sectional CT images of
bronchial tumour invasion were 82.76%, 45.45%, 80.00%, 50.00%, and 72.50%,
respectively, while the respective values for CT reconstructed images were
97.06%, 66.67%, 94.29%, 80.00%, 92.50%; these results were also statistically
significant (chi(2)=5.541, P=0.019). CONCLUSIONS: The sensitivity, specificity,
and diagnostic accuracy of the spiral CT post-processing techniques were better
than cross-sectional CT images in estimating the extent of tumour invasion in the
pulmonary arteries and bronchi of central-type NSCLC. CT post-processing
techniques are essential tools in preoperative examination and operative method
selection of central-type lung cancer with double sleeve lobectomy under c-VATS.
PMID- 27499965
TI - Robotic-assisted thoracoscopic sleeve lobectomy for locally advanced lung cancer.
AB - BACKGROUND: The Da Vinci robotic system has been used to enhance the surgeon's
visualization and agility in lung cancer surgery, and thus facilitate refined
dissection, knot tying and suturing. However, only a few case reports exist on
performing a sleeve lobectomy with a robotic-assisted thoracoscopic surgery
(RATS) technique. Here we describe our early experience performing RATS sleeve
lobectomies. To our knowledge, this is the first study reporting a series of RATS
sleeve lobectomies. METHODS: The six consecutive NSCLC patients who underwent a
RATS sleeve lobectomy between November 2013 and July 2015 at the National Taiwan
University Hospital were enrolled in this study. The lobectomies were all
performed by the same surgeon using a three-arm robotic system with an additional
utility incision made for assistance and specimen retrieval. RESULTS: Five
patients were diagnosed with squamous cell carcinoma, while the sixth was
diagnosed with a carcinoid tumor. The mean operation time was 436.7 [255-745]
minutes. The mean postoperative intensive care unit (ICU) stay and hospital stay
were 3.7 [1-11] and 11.3 [3-26] days, respectively. Two (33.3%; 2/6) morbidities
were noted, including one pneumonia and one anastomosis stricture. There were no
cases of mortality or of conversion to thoracotomy. CONCLUSIONS: Our experience
performing a RATS sleeve lobectomy in the six patients demonstrated the
feasibility of RATS in complex lung cancer surgeries. The three-dimensional
vision and articulated joint instruments made robotic-assisted bronchial
anastomosis easier under the endoscopic setting. Our experience suggests that
RATS offers specific advantages with regard to accuracy and safety when
performing sleeve lobectomies.
PMID- 27499966
TI - Assessment of epidermal growth factor receptor mutation/copy number and K-ras
mutation in esophageal cancer.
AB - BACKGROUND: The molecular status of epidermal growth factor receptor (EGFR) in
esophageal cancer has not been well elucidated. The purpose of the study was to
investigate the prevalence of EGFR and K-ras mutation, and EGFR gene copy number
status as well as its association with clinicopathologic characteristics, and
also to identify the prognostic value of EGFR gene copy number in esophageal
cancer. METHODS: EGFR mutation in exon 19/exon 21 and K-ras mutation in codon
12/codon 13 were detected by real-time PCR method, while EGFR gene copy number
status was analyzed by fluorescent in situ hybridization (FISH). EGFR gene
amplification and high polysomy were defined as high EGFR gene copy number status
(FISH-positive), and all else were defined as low EGFR gene copy number status
(FISH-negative). The relationship between EGFR gene copy number status and
clinicpathologic characteristics was analyzed. Kaplan-Meier method and Cox
proportional hazards regression model were employed to evaluate the effects of
EGFR gene copy number status on the patients' survival. RESULTS: A total of 57
esophageal squamous cell carcinoma (ESCC) patients and 9 esophageal
adenocarcinoma (EADC) patients were enrolled in the study. EGFR mutation was
identified in one patient who was diagnosed as ESCC with stage IIIC disease. K
ras mutation was identified in one patient who was diagnosed as EADC. In all, 34
of 66 (51.5%) samples were detected as FISH-positive, which includes 30 ESCC and
4 EADC tumor samples. The correlation analysis showed that FISH-positive was
significantly associated with the tumor stage (P=0.019) and lymph node metastasis
(P=0.005) in esophageal cancer patients, and FISH-positive was also significantly
associated with the tumor stage (P=0.007) and lymph node metastasis (P=0.008) in
ESCC patients. Cox regression analysis showed that high EGFR gene copy number was
not a significant predictor of a poor outcome for esophageal cancer patients
(P=0.251) or for ESCC patients (P=0.092), but esophageal cancer patients or ESCC
patients with low EGFR gene copy number may have longer survival than those with
high EGFR gene copy number according to the survival curve trends. CONCLUSIONS:
The results indicated that EGFR or K-ras mutation was rare in esophageal cancer,
but high EGFR gene copy number is frequent, and correlated with advanced
pathologic stage and more number of the metastatic regional lymph nodes,
especially in ESCC. In addition, high EGFR gene copy number is likely to have a
deleterious effect on prognosis of esophageal cancer patients or ESCC patients,
although no statistical significance was reached in the study.
PMID- 27499967
TI - Surgery of colorectal cancer lung metastases: analysis of survival, recurrence
and re-surgery.
AB - BACKGROUND: Surgery is considered an effective therapeutic option for patients
with lung metastasis (MTS) of colorectal cancer (CRC). The purpose of the study
was to evaluate efficacy and feasibility of lung metastasectomy in CRC patients
and to explore factors of prognostic relevance. METHODS: This is a retrospective
study of patients operated for lung MTS of CRC from 2004 to 2012 in a single
Institution. Overall survival (OS) was the primary endpoint. Secondary endpoints
were progression free survival (PFS) in resection status R0 and OS in in patients
submitted to re-resections. In order to evaluate prognostic factors, a
multivariable Cox proportional hazard model was performed. RESULTS: One-hundred
eighty-eight consecutive patients were included in the final analysis. The median
follow-up (FU) was 45 months. The 5-year OS and PFS were 53% (95% CI: 44-60%) and
33% (95% CI: 25-42%), respectively. Two- and 5-year survival after re-resection
were 79% (95% CI: 63-89%) and 49% (95% CI: 31-65%), respectively. Multivariate
adjusted analysis showed that primary CRC pathological TNM stages (P=0.019),
number of resected MTS >=5 (P=0.009) and lymph nodal involvement (P<0.0001) are
independent predictors of poor prognosis. CONCLUSIONS: Patients operated and re
operated for lung MTS from CRC cancers showed encouraging survival rates. Our
results indicated that primary CRC stage, number of MTS and lymph nodal
involvement are strong predictive factors. Prognosis after surgery remained
comforting up to four resected MTS. Adjuvant chemotherapy seems to have a benefit
on survival in patients affected by multiple metastases. Finally, according to
the high rate of unidentified lymph node involvement in pre-operative setting,
lymph node sampling should be advisable for a correct staging.
PMID- 27499968
TI - Positive expression of miR-361-5p indicates better prognosis for breast cancer
patients.
AB - BACKGROUND: MicroRNA-361-5p (miR-361-5p) has been reported to be tumor suppressor
in colorectal, gastric and prostate cancer, but as an oncogene in cervical
cancer. No previous research has focused on the expression of miR-361-5p and its
exact prognostic role in breast cancer (BC). METHODS: In this study, a tissue
microarray (TMA)-based miRNA detection in situ hybridization (ISH) with LNA probe
was used to detect miR-361-5p expression in 375 BC tissue. The expression level
of miR-361-5p in BC and its potential prognostic value was investigated. RESULTS:
Positive miR-361-5p staining was observed in 78.7% (N=295; 78.7% positive, 21.3%
negative) in the 375 cases. The clinical outcome of patients with positive miR
361-5p expression [median disease-free survival (DFS) time 95.52 months] was
significantly better than that of patients (median DFS time 82.33 months) with
negative miR-361-5p expression (P=0.002). Moreover, the prognostic value of miR
361-5p was most significant among patients with triple-negative breast cancer
(TNBC) for DFS (P=0.004). CONCLUSIONS: These results indicated that miR-361-5p
expression is an independent predictive factor for better prognosis in BC.
PMID- 27499969
TI - The value of esophagectomy surgical apgar score (eSAS) in predicting the risk of
major morbidity after open esophagectomy.
AB - BACKGROUND: Recently, surgical apgar score (SAS) has been reported to be strongly
associated with major morbidity after major abdominal surgery. The aim of this
study was to assess the value of esophagectomy SAS (eSAS) in predicting the risk
of major morbidity after open esophagectomy in a high volume cancer center.
METHODS: The data of all patients who admitted to intensive care unit (ICU) after
open esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences &
Peking Union Medical College from September 2008 through August 2010 was
retrospectively collected and reviewed. Preoperative and perioperative variables
were recorded and compared. The eSAS was calculated as the sum of the points of
EBL, lowest MAP and lowest HR for each patient. Patients were divided into high
risk (below the cutoff) and low-risk (above the cutoff) eSAS groups according to
the cutoff score with optimal accuracy of eSAS for major morbidity. Univariable
and multivariable regression analysis were used to define risk factors of the
occurrence of major morbidity. RESULTS: Of 189 patients, 110 patients developed
major morbidities (58.2%) and 30-day operative mortality was 5.8% (11/189). There
were 156 high risk patients (eSAS <=7) and 33 low risk (eSAS >7) patients.
Univariable analysis demonstrated that forced expiratory volume in one second of
predicted (FEV1%) <=78% (44% vs. 61%, P=0.024), McKeown approach (22.7% vs. 7.6%,
P=0.011), duration of operation longer than 230 minutes, intraoperative estimated
blood loss (347+/-263 vs. 500+/-510 mL, P=0.015) and eSAS <=7 (62.2% vs. 90.0%,
P=0.001) were predictive of major morbidity. Multivariable analysis demonstrated
that FEV1% <=78% (OR, 2.493; 95% CI, 1.279-4.858, P=0.007) and eSAS <=7 (OR,
2.810; 95% CI, 1.105-7.144; P=0.030) were independent predictors of major
morbidity after esophagectomy. Compared with patients who had eSAS >7, patients
who had eSAS <=7 had longer hospital length of stay (25.39+/-14.36 vs. 32.22+/
22.66 days, P=0.030). However, there were no significant differences in ICU
length of stay, duration of mechanical ventilation, ICU death, 30-day death rate
and in-hospital death rate between high risk and low risk patients. CONCLUSIONS:
The eSAS score is predictive of major morbidity, and lower eSAS is associated
with longer hospital length of stay in esophageal cancer patients after open
esophagectomy.
PMID- 27499970
TI - Visceral pleural invasion in lung adenocarcinoma <=3 cm with ground-glass
opacity: a clinical, pathological and radiological study.
AB - BACKGROUND: Visceral pleural invasion (VPI) had been demonstrated as an
aggressive sign in non-small cell lung cancers (NSCLC). However, its incidence
and clinical relevance in early lung cancer showing ground glass nodules (GGNs)
has not been clarified. METHODS: All consecutive surgically treated patients with
solitary GGNs between 2009 and 2013 were reviewed retrospectively. Inclusion
criteria were defined as lesions <=3 cm with pleura abutting on computed
tomography (CT) scan and pathologically confirmed NSCLC. RESULTS: Out of 156
enrolled patients, 38 had pathologically confirmed VPI. The incidence of VPI was
41.5% (27/65) if the tumor diameter was larger than 2.0 cm and 14.3% (13/91) if
diameter was smaller than 2.0 cm (P<0.001). Further, the incidence was 17.4%
(12/69) in pure GGNs and 32.2% (28/87) in part-solid GGNs (P=0.040). The tumor
size and the nodule nodule-pleural relationship were significant predictors of
positive VPI. In cases with pleural indentation, attachment, and closeness, the
incidence was 38.1%, 25.5%, and 5.3%, respectively (P=0.001). All cases were PL0
and PL1, with no PL2 cases observed. CONCLUSIONS: Although VPI was visible in
both pure/mix GGNs, it was more common in larger (>2 cm) GGNs. The radiographic
findings of nodule abutment or a pleural tag did not reliably predict or exclude
VPI. In patients with GGNs, a low rate of PL2 invasion may be observed.
PMID- 27499971
TI - Comparison of robotic and video-assisted thoracic surgery for lung cancer: a
propensity-matched analysis.
AB - BACKGROUND: Reports of comparison between robotic and thoracoscopic surgery for
lung cancer are limited, we aimed to compare the perioperative outcomes of
robotic and thoracoscopic anatomic pulmonary resection for lung cancer. METHODS:
A total of 184 patients with lung cancer underwent anatomic pulmonary resection
by robotics or thoracoscopy. A propensity-matched analysis with incorporated
preoperative variables was used to compare the perioperative outcomes between the
two procedures. RESULTS: Overall, 71 patients underwent robotic pulmonary
resection, including 64 lobectomies and 7 segmentectomies, while 113 patients
underwent thoracoscopic lobectomy and segmentectomy. Propensity match produced 69
pairs. The mean length of postoperative stay (7.6+/-4.6 vs. 6.4+/-2.6 d,
P=0.078), chest tube duration (5.3+/-3.7 vs. 4.4+/-1.7 d, P=0.056), number of
lymph nodes retrieved (17.9+/-6.9 vs. 17.4+/-7.0, P=0.660), stations of lymph
nodes resected (7.4+/-1.6 vs. 7.6+/-1.7, P=0.563), operative blood loss (53.9+/
29.3 vs. 50.3+/-37.9 mL, P=0.531), morbidity rates (42.0% vs. 30.4%, P=0.157)
were similar between the robotics and thoracoscopy. However, robotics was
associated with higher cost ($12,067+/-1,610 vs. $8,328+/-1,004, P<0.001), and
longer operative time (136+/-40 vs. 111+/-28 min, P<0.001). CONCLUSIONS: Robotics
seems to have higher hospital costs and longer operative time, without superior
advantages in morbidity rates and oncologic efficiency. Further prospective
randomized clinical trials were needed to validate both of its short- and long
term oncologic efficiency.
PMID- 27499972
TI - Outcome of veno-venous extracorporeal membrane oxygenation use in acute
respiratory distress syndrome after cardiac surgery with cardiopulmonary bypass.
AB - BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is a known risk
factor for acute respiratory distress syndrome (ARDS). We aimed to analyze the
treatment outcome in patients who required veno-venous extracorporeal membrane
oxygenation (VV-ECMO) for postcardiotomy ARDS despite other rescue modalities.
METHODS: We retrospectively reviewed the outcomes in 13 patients (mean age,
54.7+/-5.9 years) who received VV-ECMO support for refractory ARDS after cardiac
surgery between March 2013 and February 2016 at Severance Hospital, Yonsei
University (Seoul, Korea). RESULTS: At the start of VV-ECMO, the average lung
injury score was 3.0+/-0.2, and the Respiratory Extracorporeal Membrane
Oxygenation Survival Prediction (RESP) score was -4+/-1.1. Although 7 patients
initiated VV-ECMO support within 24 h from operation, the remaining 6 started at
a median of 8.5 days (range, 5-16 days). Nine (69.3%) patients were successfully
weaned from VV-ECMO. After a median follow-up duration of 14.5 months (range, 1.0
33.0 months) for survivors, the 1-year overall survival was 58.6%+/-14.4%. The
differences in the overall survival from VV-ECMO according to the RESP score risk
classes were borderline significant (100% in class III, 50%+/-25% in class IV,
and 20%+/-17.9% in class V; P=0.088). CONCLUSIONS: VV-ECMO support can be a
feasible rescue strategy for adult patients who develop refractory ARDS after a
cardiac surgery. Additionally, the RESP score seems a valuable prognostic tool
for post-ECMO survival outcome in this patient population as well.
PMID- 27499973
TI - Efficacy of subpleural continuous infusion of local anesthetics after
thoracoscopic pulmonary resection for primary lung cancer compared to intravenous
patient-controlled analgesia.
AB - BACKGROUND: This study compared the efficacy and side effects of intravenous
patient-controlled analgesia (IV-PCA) with those of a subpleural continuous
infusion of local anesthetic (ON-Q system) in patients undergoing thoracoscopic
pulmonary resection for primary lung cancer. METHODS: We retrospectively reviewed
66 patients who underwent thoracoscopic pulmonary resection for primary lung
cancer from January 2014 to August 2015 (36 in the IV-PCA group and 30 in the ON
Q group). The numeric pain intensity scale (NPIS), additional IV injections for
pain control, side effects, and early discontinuation of the pain control device
were compared. RESULTS: There were no differences in the general characteristics
of the two groups. The NPIS scores gradually decreased with time (P<0.001), but
the two groups had differences in pattern of NPIS scores (P=0.111). There were no
differences in the highest NPIS score during admission (4.75+/-2.35 vs. 5.27+/
1.87, P=0.334) or the number of additional IV injections for pain control in the
same period (0.72+/-0.94 for IV-PCA vs. 0.83+/-0.65 for ON-Q; P=0.575). Side
effects such as nausea, dizziness, and drowsiness were significantly more
frequent with IV-PCA (36.1% vs. 10.0%, P=0.014), and early discontinuation of the
pain control device was more frequent in the IV-PCA group (33.3% vs. 6.7%,
P=0.008). CONCLUSIONS: The ON-Q system was equivalent to the IV-PCA for
postoperative pain control after thoracoscopic pulmonary resection for primary
lung cancer, and it also had fewer effects and early discontinuations.
PMID- 27499974
TI - Short-term effects of a vibrotactile neck-based treatment device for positional
obstructive sleep apnea: preliminary data on tolerability and efficacy.
AB - BACKGROUND: Positional supine obstructive sleep apnea syndrome (OSAS)
characterizes a subgroup of patients suffering from OSAS. Several devices
designed to limit supine position have been developed, but evidences of their
efficacy and safety are lacking. It is unclear whether a neck-worn vibrating
device could induce positional change in patients with positional OSAS. We
evaluated the efficacy of a neck-worn device to induce supine avoidance
positional feedback over a short-term trial in OSAS patients and its impact on
sleep quality and polysomnographyc indexes. METHODS: Twenty patients with
positional apneas/hypopneas were prospectively studied. Baseline characteristics
of daytime somnolence and risk of sleep apnea were screened and the efficacy of a
3-day trial of supine-avoidance therapy by vibrotactile neck worn device assessed
by reporting the self-perceived change in quality of sleep and performing cardio
respiratory polysomnography. Comparison between baseline and treatment results
was performed. RESULTS: The neck device produced a reduction in overall apnea
hypopnea index (AHI) (mean AHI pre =16.8/h and post =4.4/h, P<0.0001), oxygen
desaturation (pre =13.7/h and post =3.8/h, P<0.0001) and Respiratory Disturbance
Indexes (RDI) (20.0/h vs. 5.2/h; P<0.0001).The time spent in supine position
decreased from 62.1% to 33.7% of the total (P<0.001). However, the impact on the
perceived quality of sleep was unpredictable. CONCLUSIONS: The neck position
therapy device is effective in restricting supine sleep, improving AHI and
related polysomnographic indexes. However, at least in a short-term trial, it
seems unable to improve the patient's sleep quality.
PMID- 27499975
TI - Urgent pulmonary lobectomy for blunt chest trauma: report of three cases without
mortality.
AB - BACKGROUND: The majority of patients with severe blunt chest trauma is
successfully treated with supportive measures and thoracostomy tube; only few
cases need urgent thoracotomy. Lung-sparing techniques are treatments of choice
but major pulmonary resections are necessary in case of injuries involving hilar
vessels or bronchi. Currently the mortality associated with pulmonary lobectomy
performed for chest trauma is 40%. METHODS: Over a 2-year period [2013-2014], 210
patients with chest trauma were hospitalized at our Institution. Mechanism of
injury was blunt in 204 (97.1%) patients and penetrating in 6 (2.9%). In 48
(22.8%) patients was necessary a ventilatory support and 37 (17.6%) patients were
treated with thoracostomy tube. Nineteen (9%) patients needed urgent thoracotomy:
4 (1.9%) cases for penetrating injury and 15 (7.1%) cases for blunt trauma. Three
(1.4%) patients treated with urgent thoracotomy required concomitant laparotomy
for intra-abdominal injuries. The overall mortality rate was 1.4%. RESULTS: We
report three cases of urgent lobectomies for chest trauma without mortality and
with postoperative complete restoration of respiratory function. The anatomical
lobectomies were performed for: massive hemothorax with bronchial disruption,
expanding pulmonary hematoma with hypovolemic shock, and massive hemothorax in
deep parenchymal laceration. CONCLUSIONS: Mortality rate after major pulmonary
resections for trauma is very high and increases with the presence of
multivisceral injuries, the severity of hypovolemic shock and extent of lung
resection. Anterolateral thoracotomy was the approach employed in case of cardiac
arrest. In hypovolemic patients a posterolateral incision with a double lumen
intubation was performed. The absence of mortality in this series may be related
to the prompt diagnosis, short operative time and absence of associated severe
neurological or abdominal injuries.
PMID- 27499976
TI - Uniportal video-assisted thoracoscopic lobectomy for lung cancer.
AB - Great advances have been made in the multi-port video-assisted thoracoscopic
surgery lobectomy in the recent two decades. However, only five years passed a
more minimally surgery, namely uniportal video-assisted thoracoscopic lobectomy,
was launched. Accumulating experience and exploration are being performed in most
of the medical centres and hence we summarize the experience of uniportal video
assisted thoracoscopic lobectomy in our operation group.
PMID- 27499977
TI - Minimally invasive surgery for esophageal achalasia.
AB - Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused
by esophageal functional disease. Its main feature is the lack of esophageal
peristalsis, the lower esophageal sphincter pressure and to reduce the swallow's
relaxation response. Lower esophageal muscular dissection is one of the main ways
to treat esophageal achalasia. At present, the period of muscular layer under the
thoracoscope esophagus dissection is one of the treatment of esophageal
achalasia. Combined with our experience in minimally invasive esophageal surgery,
to improved incision and operation procedure, and adopts the model of the
complete period of muscular layer under the thoracoscope esophagus dissection in
the treatment of esophageal achalasia.
PMID- 27499978
TI - Uniportal video-assisted thoracic surgery resection of small ground-glass
opacities (GGOs) localized with CT-guided placement of microcoils and palpation.
AB - Although uniportal video-assisted thoracic surgery (VATS) is becoming more
popular, it's still very challenging to conduct a wedge resection of small
pulmonary ground-glass opacities (GGOs), especially deeply situated subpleural
GGOs, via uniportal VATS. We successfully performed thirteen uniportal VATS wedge
resections through an approach that combines radiologically guided microcoil
localization with palpation, and we encountered no complications related to the
new approach. Based on our experience, a combination of CT-guided microcoil
localization with palpation in uniportal VATS for deeply situated subpleural GGOs
is a safe and effective procedure for accurate diag!nosis and resection of
indeterminate GGOs.
PMID- 27499979
TI - Clinical application of near-infrared thoracoscope with indocyanine green in
video-assisted thoracoscopic bullectomy.
AB - Failure to identify all the possible bullous lesions was considered an important
reason for the higher recurrence rate after the VATS bullectomy. We applied the
latest near-infrared (NIR) thoracoscope with indocyanine green (ICG) to detect
bullous lesions for patients with spontaneous pneumothorax. Two male patients
with spontaneous pneumothorax and poorly identified bullae intraoperatively were
included in this pilot study. An NIR thoracoscope with two different doses of ICG
injection (0.2 and 0.6 mg/kg) was used to detect bullous lesions during VATS
bullectomy. Partial lung resections of the bullous lesions were performed under
syncretic mode. Data was managed with ImageJ software. No procedure-related
complications were observed. The fluorescent signal was detected in normal lung
tissue 10.5 seconds (mean, 10-11 seconds) after the ICG bolus, and lasted up to
525 seconds (mean, 480-570 seconds). The bullous lesions showed an obviously
decreased fluorescent densities comparing to adjacent normal tissue. At the
dosage of 0.6 mg/kg, ICG emits sufficient fluorescence to demonstrate the precise
border of bullae, with the max SBR of 6.32. All resected specimens were confirmed
as bullous lesions microscopically. NIR thoracoscope with intravenous ICG is a
safe, accurate and real-time method to detect bullous lesions of lung tissue
difficult to be found under normal light in human subjects. TRIAL REGISTRATION:
NCT02611245 (https://register.clinicaltrials.gov/).
PMID- 27499980
TI - Surgery and pleuro-pulmonary tuberculosis: a scientific literature review.
AB - Tuberculosis (TB) is still a major public health concern, mostly affecting
resource-constrained settings and marginalized populations. The fight against the
disease is hindered by the growing emergence of drug-resistant forms whose
management can be rather challenging. Surgery may play an important role to
support diagnosis and treatment of the most complex cases and improve their
therapeutic outcome. We conducted a non-systematic review of the literature based
on relevant keywords through PubMed database. Papers in English and Russian were
included. The search was focused on five main areas of intervention as follows:
(I) diagnosis of complicated cases; (II) elimination of contagious persisting
cavities, despite appropriate chemotherapy; (III) treatment of destroyed lung;
(V) resection of tuberculomas; (VI) treatment of tuberculous pleural empyema.
Although specific practical guidelines concerning surgical indications and
approaches are currently unavailable, a summary of the evidence emerged from the
scientific literature was elaborated to help the clinician in the management of
severely compromised TB patients. The decision to proceed to surgery is usually
individualized and a careful assessment of the patient's risk profile is always
recommended before performing any procedure in addition to appropriate
chemotherapy.
PMID- 27499981
TI - Tuberculous pleural effusion.
AB - Although it is curable, tuberculosis remains one of the most frequent causes of
pleural effusions on a global scale, especially in developing countries.
Tuberculous pleural effusion (TPE) is one of the most common forms of
extrapulmonary tuberculosis. TPE usually presents as an acute illness with fever,
cough and pleuritic chest pain. The pleural fluid is an exudate that usually has
predominantly lymphocytes. The gold standard for the diagnosis of TPE remains the
detection of Mycobacterium tuberculosis in pleural fluid, or pleural biopsy
specimens, either by microscopy and/or culture, or the histological demonstration
of caseating granulomas in the pleura along with acid fast bacilli, Although
adenosine deaminase and interferon-gamma in pleural fluid have been documented to
be useful tests for the diagnosis of TPE. It can be accepted that in areas with
high tuberculosis prevalence, the easiest way to establish the diagnosis of TPE
in a patient with a lymphocytic pleural effusion is to generally demonstrate a
adenosine deaminase level above 40 U/L. The recommended treatment for TPE is a
regimen with isoniazid, rifampin, and pyrazinamide for two months followed by
four months of two drugs, isoniazid and rifampin.
PMID- 27499982
TI - Veno-arterial extracorporeal membrane oxygenation for cardiogenic shock due to
myocarditis in adult patients.
AB - Myocarditis is an inflammatory disease of the heart muscle with established
histological, immunological and immunohistochemical diagnostic criteria.
Different triggers could be advocated as possible etiologies of myocarditis such
as viral and non-viral infections, medications, systemic autoimmune diseases and
toxic reactions. The spectrum of clinical presentations of myocarditis is broad
and varies from subclinical asymptomatic courses to refractory cardiogenic shock.
The prognosis of patients with myocarditis depends mainly on the severity of
clinical presentation. In particular, myocarditis patients developing cardiogenic
shock refractory to optimal maximal medical treatment may benefit from the use of
veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as a temporary
mechanical circulatory support (MCS). The aim of the present report is to offer a
review of the most important articles of the literature showing the results of VA
ECMO in the specific setting of cardiogenic shock due to myocarditis in adult
patients.
PMID- 27499983
TI - When size matters: changing opinion in the management of pleural space-the rise
of small-bore pleural catheters.
AB - Tube thoracostomy is usually the first step to treat several thoracic/pleural
conditions such as pneumothorax, pleural effusions, haemothorax, haemo
pneumothorax and empyema. Today, a wide range of drains is available, ranging
from small to large bore ones. Indications for an appropriate selection remains
yet matter of debate, especially regarding the use of small bore catheters.
Through this paper, we aimed to retrace the improvements of drains through the
years and to review the current clinical indications for chest drain placement in
pleural/thoracic diseases, comparing the effectiveness of small-bore drains vs.
large-bore ones.
PMID- 27499984
TI - Post hoc ergo propter hoc.
PMID- 27499985
TI - Free jejunum interposition as salvage surgery after cervical esophagus injury.
AB - In rare cases when stomach could not be suitable for esophageal replacement, the
jejunum should probably be suitable for esophageal reconstruction. However, the
widespread prevalence of jejunal interposition is precluded because of its
complexity. Here we present a case of a 74-year-old female who underwent free
jejunal interposition as salvage surgery. In this case, cervical esophagus was
injured during thyroidectomy. Nine months later, replacement of injured part of
esophagus with free jejunum was performed. End-to-end and end-to-side anastomosis
were used for esophagus-jejunum and vascular-to-vascular anastomosis
respectively. This patient was discharged from hospital 15 days postoperatively.
No severe postoperative complication happened. Only minor late operation
complication (anastomotic stricture) occurred during 13 years of annual follow
up.
PMID- 27499986
TI - Partial anomalous venous drainage of the left upper lobe during a robot-assisted
pulmonary resection.
AB - Anomalies in pulmonary vasculature are rare; however, the knowledge of the anomal
and potential physiological implications for a patient undergoing a thoracic
surgery must be understood. We report a case of a 64-year-old female who had a
robotic left upper lobectomy for an incidental pulmonary nodule and was found to
have a partial anomalous pulmonary vein. We discuss the incidence of pulmonary
vein anomalies, associated conditions, and surgical management in patients
requiring thoracic surgery.
PMID- 27499987
TI - Dissecting thoracic aortic aneurysm associated with tuberculous pleural effusion.
AB - We present the case of thoracic aortic aneurysm associated with the tuberculous
pleural effusion. An 82-year-old woman underwent emergency stent graft under a
diagnosis of dissecting thoracic aortic aneurysm. Preoperative computed
tomography revealed right pleural effusion supposed to the hemothorax caused by
the dissecting aneurysm. But, the effusion was sanguineous color fluid and it was
determined to result from pulmonary tuberculosis. The medical team was exposed to
the pulmonary tuberculosis; fortunately no one became infected. Physicians should
be aware of the possibility of an infected aortic aneurysm and prepare for
pathogen transmission.
PMID- 27499988
TI - Delayed aortic rupture resulting from postoperative superficial sternal wound
infection.
AB - While deep sternal wound infection (DSWI) after cardiac surgery is a significant
contributor to patient morbidity and mortality, superficial sternal wound
infection (SSWI) mostly has a benign course. We report a mortality case of aortic
rupture resulting from SSWI after cardiac surgery. A 50-year-old male underwent
an aortic valve replacement (AVR). Three months after the valve operation, he
presented with severe dyspnea, which had never before been observed, and chest
computed tomography revealed an ascending aortic rupture with large hematoma
compressing the main pulmonary artery. We performed an emergent operation for
aortic rupture that possibly originated from the SSWI. Postoperatively, the
patient died of hypovolemic shock due to recurrent aortic rupture despite efforts
to resuscitate him.
PMID- 27499989
TI - Hypoxemia associated with right-side cardiac tumor: right atrial lymphoma with
patent foramen ovale.
AB - A 66-year-old man presented with acute type I respiratory failure, and was
diagnosed to have a huge mass occupying the right atrium (RA) of the heart, with
no evidence of pulmonary embolism. Intra-operative transesophageal echocardiogram
identified a patent foramen ovale (PFO) with right-to-left shunt apart from a
huge right atrial tumor arising from the atrioventricular groove. The tumor was
debulked, and the patent foramen was closed. Patient had an uneventful recovery
and WAS discharged on post-operative day 7. Pathology revealed diffuse large B
cell lymphoma (DLBCL). The patient was further treated with adjuvant chemotherapy
and remained well 1 year after surgery. This case illustrates the importance of
meticulous echocardiographic examination to look for any intracardiac shunts in
the case of hypoxemia associated with a right-sided cardiac tumor. We advocate
surgery as the most important initial management to maximize survival, as it
allows correction of any hemodynamic sequelae, and simultaneous attainment of
definite histological diagnosis for guidance of adjuvant therapy.
PMID- 27499990
TI - Simultaneous resection of left atrial myxoma and esophageal carcinoma via right
thoraco-abdominal approach.
AB - Concomitant occurrence of atrial myxoma and esophageal carcinoma is an extremely
rare entity. Here we present two cases of synchronously suffered left atrial
myxoma and esophageal carcinoma. Both patients underwent simultaneous resection
of two tumors via the right thoraco-abdominal approach and recovered well.
PMID- 27499991
TI - Dramatic response to anti-PD-1 therapy in a patient of squamous cell carcinoma of
thymus with multiple lung metastases.
AB - Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its
ligand PD-L1 has demonstrated efficacy in some malignancies, such as metastatic
melanoma and non-small-cell lung cancer (NSCLC). Compared with cytotoxic
chemotherapy, radiotherapy or molecular targeted agent, it is an innovative way
to treat malignancies with durable clinical responses and manageable adverse. We
present a case of female patient with squamous cell carcinoma of thymus involving
multiple lung metastases, who was successfully treated with anti-PD-1 monoclonal
antibody, pembrolizumab.
PMID- 27499992
TI - Exophiala pisciphila: a novel cause of allergic bronchopulmonary mycosis.
AB - Allergic bronchopulmonary mycosis (ABPM) is a hypersensitivity reaction to fungal
antigens, which may particularly plague uncontrolled asthmatics. Non-aspergillus
fungal organisms may be implicated and may elicit a more severe immunologic
response. Exophiala pisciphila, a marine organism, has not been reported as a
culprit yet. However, this report indicates it may be implicated in unrelenting
symptoms in a severe asthmatic patient who had become dependent on
corticosteroids. Proper identification and adequate therapy of this organism led
to complete resolution of respiratory symptoms, with adequate subsequent control
of the asthma. ABPM may complicate asthma and lead to a lack of its control.
Proper awareness, testing and treatment of non-aspergillus pulmonary mycosis is
essential to proper asthma care and beneficial for its control.
PMID- 27499993
TI - Exon 19 L747P mutation presented as a primary resistance to EGFR-TKI: a case
report.
AB - Active mutations of the EGFR gene have been proved to predict the activity of
EGFR-TKI. The most common mutations are the exon 19 deletion and exon 21 point
mutation, both of which are sensitive to EGFR-TKI. However, rare EGFR mutations
or complex mutations still exist, and data of which are scarce and controversial.
Their response to EGFR-TKI remains uncertain. We presented a patient diagnosed
with stage IV lung adenocarcinoma who was found to have the EGFR mutation in exon
19 (L747P) before any treatment. The disease progressed 2 months after the
chemotherapy containing cisplatin and pemetrexed, and erlotinib was administered,
but there was no response found. This EGFR-TKI naive patient failed to achieve
the desired effect with the therapy of EGFR-TKI. L747P may be associated with
primary resistance to EGFR-TKI in this case.
PMID- 27499994
TI - A 30-year-old female Behcet's disease patient with recurrent pleural and
pericardial effusion and elevated adenosine deaminase levels: case report.
AB - Behcet's disease is a systemic disease which may involve various organs. We
describe a case of a patient diagnosed as pleuropericardial involvement of
Behcet's disease. A 30-year-old woman visited our clinic presented with left
pleuritic chest pain for s days. She had been diagnosed as Behcet's disease and
admitted to our clinic due to pericardial and pleural effusion repeatedly in past
two years. In the previous studies, effusion analysis revealed to be lympho
dominant exudate with high adenosine deaminase level. Acid-fast bacilli (AFB)
culture and polymerase chain reaction (PCR) for mycobacterial tuberculosis (M.TB)
were negative in the pericardial tissue, and pathologic finding showed mild
endothelitis with micro-thrombi formation in the lumen. The patient had been
treated with antituberculous medication for a year. In the current admission,
chest computed tomography (CT) again showed left pleural effusion without other
significant lesion. Pleural fluid analysis was similar with the previous study.
Video-assisted thoracoscopic pleural biopsy was performed to obtain the definite
diagnosis. Pathology confirmed the diagnosis as pleuropericardial involvement of
Behcet's disease, and we treated the patient with oral steroid in the out-patient
department. Pleuropericardial involvement of Behcet's disease may mimic TB
pleurisy or pericarditis due to high adenosine deaminase (ADA) level in effusion
analysis. Clinicians should keep in mind that Behcet's disease may manifest as
pleural or pericardial effusion, and pathologic confirmation could be helpful for
the definite diagnosis.
PMID- 27499995
TI - Acetaminophen to treat fever in intensive care unit patients with likely
infection: a response from the author of the HEAT trial.
PMID- 27499996
TI - Professor Wolfgang Oertel: research on Parkinson Disease-big step forward, more
problems to research.
PMID- 27499997
TI - Professor Gian Paolo Rossi: special hypertension patient-why blood pressure at
night is higher than that in the daytime?
PMID- 27499998
TI - Erratum to non-intubated combined with video-assisted thoracoscopic in carinal
reconstruction.
AB - [This corrects the article DOI: 10.21037/jtd.2016.01.58.].
PMID- 27499999
TI - Time to get real: critical and imperative change required in evidence evaluation.
PMID- 27500000
TI - 2016 Respiratory Effectiveness Group Annual Summit Report-impact & influence of
real-world respiratory evidence.
PMID- 27500002
TI - Leveraging datasets and insisting on quality to address unmet research needs-the
epidemiologists' dream.
PMID- 27500001
TI - The role of primary care databases in developing asthma and allergy service
delivery.
PMID- 27500003
TI - Routine primary care data-the new crystal ball?
PMID- 27500004
TI - Xanthomatous hypophysitis associated with autoimmune disease in an elderly
patient: A rare case report.
AB - BACKGROUND: Xanthomatous hypophysitis (XH) is an extremely rare form of primary
hypophysitis characterized by infiltration of the pituitary gland by mixed types
of inflammatory cells, including foamy cells, plasma cells, and small mature
lymphocytes. XH manifests as varying degrees of hypopituitarism. Although several
previous reports have denied a possible contribution of autoimmune mechanism, the
exact pathogenesis of XH remains unclear. CASE DESCRIPTION: We describe the case
of a 72-year-old woman with a history of rheumatoid arthritis and Sjogren's
syndrome who presented with panhypopituitarism and diabetes insipidus. At the
time of her visit, she also experienced relapsed rheumatoid arthritis and
Sjogren's syndrome, manifesting as arthralgia. Magnetic resonance imaging (MRI)
showed a multicystic mass in the sellar and suprasellar regions. In the course of
steroid replacement therapy for hypocortisolism, the patient's arthralgia
diminished, and MRI revealed shrinkage of the mass. XH was diagnosed
histologically following a transsphenoidal endoscopic biopsy, and it was the
oldest case of XH. CONCLUSION: To the best of our knowledge, this patient is the
oldest of reported patients diagnosed with XH. Steroid therapy may be effective
to XH temporarily. XH should be considered when diagnosing pituitary cystic
lesions in elderly patients with autoimmune disease.
PMID- 27500005
TI - Operative surgical nuances of modified extradural temporopolar approach with mini
peeling of dura propria based on cadaveric anatomical study of lateral cavernous
structures.
AB - BACKGROUND: Extradural temporopolar approach (ETA) has been modified as less
invasive manner and named as trans-superior orbital fissure (SOF) approach with
mini-peeling technique. The present study discusses the operative nuances of this
modified technique on the basis of cadaveric study of lateral cavernous
structures. METHODS: In five consecutive cadaveric specimens, we performed an
extradural anterior clinoidectomy with mini-peeling of the dura propria to expose
the anterior clinoid process entirely. We also investigated the histological
characteristics of the lateral cavernous sinus (CS) between the dura propria and
periosteal dura at the SOF, foramen rotundum (FR), and foramen ovale (FO) levels,
and of each trigeminal nerve division. RESULTS: Coronal histological examination
of the lateral wall of the CS showed invagination of the dura propria and
periosteal dura into the SOF. In contrast, no such invagination was observed at
the levels of the FR and FO. This finding supports the technical rationale of the
only skeletonization of the SOF for peeling of the dura propria but not FR. In
addition, our modified ETA method needs only minimal dural incision between the
SOF and FR where no cranial nerves are present. CONCLUSION: Our technical
modification of ETA may be recommended for surgical treatment of paraclinoid
lesions to reduce the risk of intraoperative neurovascular injury.
PMID- 27500006
TI - Subarachnoid hemorrhage caused by an undifferentiated sarcoma of the sellar
region.
AB - BACKGROUND: It is rare for patients with pituitary apoplexy to exhibit
concomitant subarachnoid hemorrhage (SAH). Only a handful of patients with
pituitary apoplexy have developed such hemorrhagic complications, and
histopathological examination revealed pituitary adenoma as the cause of SAH.
CASE REPORT: A previously healthy 35-year-old woman was brought to our
institution after complaining of severe headache and left monocular blindness.
Brain computed tomography showed a diffuse SAH with a central low density.
Subsequently, the brain magnetic resonance imaging revealed an intrasellar mass
with heterogeneous contrast enhancement. The patient was presumptively diagnosed
with SAH secondary to hemorrhagic pituitary adenoma and underwent transcranial
surgery to remove both the tumor and subarachnoid clot. A histological evaluation
of the surgical specimen revealed malignant cells with strong predilection for
vascular invasion. Following immunohistochemical evaluation, the tumor was
negative for the majority of tumor markers and was positive only for vimentin and
p53; thus, a diagnosis of undifferentiated sarcoma was established. CONCLUSIONS:
This case was informative in the respect that tumors other than pituitary adenoma
should be included in the differential diagnosis of patients with pituitary
apoplexy.
PMID- 27500007
TI - Dural repair using autologous fat: Our experience and review of the literature.
AB - BACKGROUND: Various materials have been proposed to obliterate dead spaces and to
reconstruct dural defects during a neurosurgical approach. This study describes
our technique of using the abdominal autologous fat graft and evaluates the
complications and characteristics related to the use of this tissue during
cranial procedures. METHODS: Autologous fat grafts were used in 296 patients with
basicranial and convexity extraaxial tumors from April 2005 to January 2015. The
adipose tissue was removed from the paraumbilical abdominal region and was
transformed into a thin foil. When possible, a watertight suture was made between
the dural or bone edge with a fat graft. We always used fibrin glue to reinforce
the dural closure. RESULTS: Complications occurred between 2 days and 1 year
following procedure. Cerebrospinal fluid leaks were found in 11 cases. No case of
mortality, pseudomeningoceles, fistula, infections, bacterial meningitides, or
lipoid meningitides was reported. No patient required removal of the graft. No
adhesion was observed between the brain and the autologous fat. Other fat-related
complications observed were 2 cases of fat necrosis in the abdomen and 2 cases of
abdominal hemorrhage. CONCLUSION: The technique of harvesting and applying fat
grafts is fairly simple, although it must be performed meticulously to be
effective. Our experience has led us to believe that the use of fat grafts
presents low morbidity and mortality. However, a neurosurgeon should never forget
the possible late or early complications related to the use of fat grafts.
PMID- 27500008
TI - Neurofibromatosis type 1 and Chiari type 1 malformation: A case report and
literature review of a rare association.
AB - BACKGROUND: The association between neurofibromatosis type 1 (NF-I) and Chiari I
malformation (CMI) is rare, and not many studies are reported in the literature.
Performing magnetic resonance imaging (MRI) in patients with NF-1 is essential
because several cases of Chiari type I are completely asymptomatic. We emphasize
the need for inclusion of Chiari I as diagnosis in association with NF-1. CASE
DESCRIPTION: The patient was a 51-year-old black man who presented with
complaints of pain and decreased motion and sensibility of his hands, wrists, and
forearms, along with progressive dysarthria. Even though the computed tomography
(CT) scan of the skull did not show changes, the MRI showed hydro/syringomyelia
in the cervical spine area. Midline suboccipital craniectomy with total
laminectomy of c1 and partial laminectomy of c2 was performed; tonsillectomy was
also performed for cistern expansion because of intense thickening and
obliteration of the obex by the cerebellar tonsils. Following treatment, the
patient showed remission of symptoms. CONCLUSION: NF-1 in association with CMI is
rare, and early diagnosis and surgical treatment are essential to slow down the
myelopathy; although they prevent neurological damages, patients with NF-1 must
remain under doctor's attention in case of association with CMI. Our literature
review showed that symptoms can vary and include headache, gait disturbance, and
sensory/motor diminution, until asymptomatic patients. Moreover, the incidence of
NF-1 is considerably higher in CMI patients in comparison to the global incidence
(8.6-11.8% and 0.775%, respectively). The surgical technique must be evaluated
case by case according to the degree of cerebrospinal fluid obstruction.
PMID- 27500009
TI - Creation of Interpretable Summary Measures in Displaying Results from Mixed
effects Logit Models.
AB - The authors of this article developed new approaches to present analytic results
from mixed-effects binary logit models in longitudinal data analysis. We first
described basic specifications of mixed-effects logit models, the derivation of
the fixed and the random effects, and nonlinear predictions of the response
probability and the corresponding standard errors. Particular attention was paid
to the interpretability of the conventional odds ratio in the longitudinal
setting. The authors contended that without information on averaging of the
random effects for two population subgroups of interest, the regression
coefficient of an explanatory variable and its antilog in mixed-effects binary
logit models are not interpretable. We recommended the computation of the
conditional effect and the conditional odds ratio to aid in displaying a
covariate's effect on the longitudinal binary response. An empirical illustration
was provided to demonstrate how to create interpretable summary measures for
aiding in the interpretation of the results from mixed-effects logit models when
analyzing binary longitudinal data.
PMID- 27500010
TI - Codified Hashtags for Weather Warning on Twitter: an Italian Case Study.
AB - INTRODUCTION: During emergencies increasing numbers of messages are shared
through social media platforms becoming a primary source of information for lay
people and emergency managers. For Twitter codified hashtagging is emerging as a
practical way to coordinate messages during emergencies and quickly identify
relevant information. This paper considers a case study on the use of codified
hashtags concerning weather warning in Italy in three different regions. METHODS:
From November 3rd to December 2nd 2014, tweets identified by the 3 codified
hashtags #allertameteoTOS, #allertameteoLIG and #allertameteoPIE were retrieved,
collecting a total of 35,558 tweets published by 7361 unique tweets authors, with
the aim to assess if codified hashtags could represent an effective way to align
formal and informal sources of information during weather related emergencies. An
auxiliary R-package was built to lead the analytics used in this study. Authors
performed a manual coding of users, hashtags and content of messages of all
Twitter data considered. RESULTS: Content analysis showed that tweets were
overwhelmingly related to situational updates, with a high percentage containing
geo-location information. Communication patterns of different user types were
discussed for the three contexts. In accordance with previous studies,
individuals showed an active participation primarily functioning as information
hub during the emergency. DISCUSSION: In the proposed cases codified hashtags
have proven to be an effective tool to convey useful information on Twitter by
formal and informal sources. Where institutions supported the use of the
predefined hashtag in communication activities, like in Tuscany, messages were
very focused, with more than 90% of tweets being situational updates. In this
perspective, use of codified hashtags may potentially improve the performance of
systems for automatic information retrieval and processing during disasters.
PMID- 27500011
TI - Can Quantitative Muscle Strength and Functional Motor Ability Differentiate the
Influence of Age and Corticosteroids in Ambulatory Boys with Duchenne Muscular
Dystrophy?
AB - BACKGROUND: In the absence of a curative treatment for Duchenne Muscular
Dystrophy (DMD), corticosteroid therapy (prednisone, deflazacort) has been
adopted as the standard of care, as it slows the progression of muscle weakness
and enables longer retention of functional mobility. The ongoing development of
novel pharmacological agents that target the genetic defect underlying DMD offer
hope for a significant alteration in disease progression; however, substantiation
of therapeutic efficacy has proved challenging. Identifying functional outcomes
sensitive to the early, subtle changes in muscle function has confounded clinical
trials. Additionally, the alterations in disease progression secondary to
corticosteroid therapy are not well described making it difficult to ascertain
the benefits of novel agents, often taken concurrently with corticosteroids.
OBJECTIVE: The purpose of this study was to examine outcome responsiveness to
corticosteroid therapy and age at the onset of a natural history study of
ambulatory boys with DMD. METHODS: Eighty-five ambulatory boys with DMD (mean age
93 mo, range 49 to 180 mo) were recruited into this study. Fifty participants
were on corticosteroid therapy, while 33 were corticosteroid naive at the
baseline assessment. Within each treatment group boys were divided in two age
groups, 4 to 7 years and 8 and greater years of age. The Biodex System 3 Pro
isokinetic dynamometer was used to assess muscle strength. Motor skills were
assessed using the upper two dimensions (standing/walking, running & jumping) of
the Gross Motor Function Measure (GMFM 88) and Timed Motor Tests (TMTs) (10-meter
run, sit to stand, supine to stand, climb 4-stairs). Two way analysis of variance
and Pearson correlations were used for analysis. RESULTS: A main effect for age
was seen in select lower extremity muscle groups (hip flexors, knee extensors and
ankle dorsiflexors), standing dimension skills, and all TMTs with significantly
greater weakness and loss of motor skill ability seen in the older age group
regardless of treatment group. Interaction effects were seen for the walking,
running, and jumping dimension of the GMFM with the naive boys scoring higher in
the younger group and boys on corticosteroid therapy scoring higher in the older
group. The TMT of climb 4-stairs demonstrated a significant treatment effect with
the boys on corticosteroid therapy climbing stairs faster than those who were
naive, regardless of age. Examination of individual items within the upper level
GMFM dimensions revealed select motor skills are more informative of disease
progression than others; indicating their potential to be sensitive indicators of
alterations in disease progression and intervention efficacy. Analysis of the
relationship between muscle group strength and motor skill performance revealed
differences in use patterns in the corticosteroid versus naive boys. CONCLUSION:
Significant muscle weakness is apparent in young boys with DMD regardless of
corticosteroid treatment; however, older boys on corticosteroid therapy tend to
have greater retention of muscle strength and motor skill ability than those who
are naive. Quantification of muscle strength via isokinetic dynamometry is
feasible and sensitive to the variable rates of disease progression in lower
extremity muscle groups, but possibly most informative are the subtle changes in
the performance characteristics of select motor skills. Further analysis of
longitudinal data from this study will explore the influence of corticosteroid
therapy on muscle strength and further clarify its impact on motor performance.
PMID- 27500012
TI - Coping Strategies for Landslide and Flood Disasters: A Qualitative Study of Mt.
Elgon Region, Uganda.
AB - INTRODUCTION: The occurrence of landslides and floods in East Africa has
increased over the past decades with enormous Public Health implications and
massive alterations in the lives of those affected. In Uganda, the Elgon region
is reported to have the highest occurrence of landslides and floods making this
area vulnerable. This study aimed at understanding both coping strategies and the
underlying causes of vulnerability to landslides and floods in the Mt. Elgon
region. METHODS: We conducted a qualitative study in three districts of Bududa,
Manafwa and Butalejja in the Mt. Elgon region in eastern Uganda. Six Focus Group
Discussions (FGDs) and eight Key Informant Interviews (KIIs) were conducted. We
used trained research assistants (moderator and note taker) to collect data. All
discussions were audio taped, and were transcribed verbatim before analysis. We
explored both coping strategies and underlying causes of vulnerability. Data were
analysed using latent content analysis; through identifying codes from which
basis categories were generated and grouped into themes. RESULTS: The positive
coping strategies used to deal with landslides and floods included adoption of
good farming methods, support from government and other partners, livelihood
diversification and using indigenous knowledge in weather forecasting and
preparedness. Relocation was identified as unsustainable because people often
returned back to high risk areas. The key underlying causes of vulnerability
were; poverty, population pressure making people move to high risk areas,
unsatisfactory knowledge on disaster preparedness and, cultural beliefs affecting
people's ability to cope. CONCLUSION: This study revealed that deep rooted links
to poverty, culture and unsatisfactory knowledge on disaster preparedness were
responsible for failure to overcome the effects to landslides and floods in
disaster prone communities of Uganda. However, good farming practices and support
from the government and implementation partners were shown to be effective in
enabling the community to lessen the negative effects disasters. This calls for
high impact innovative interventions focused in addressing these underlying
causes as well as involvement of all stakeholders in scaling the effective coping
strategies in order to build resilience in this community and other similarly
affected areas. KEY WORDS: Coping, Underlying causes, Floods, Landslides, Mt.
Elgon, Uganda.
PMID- 27500013
TI - Effectiveness of Synchronized Noninvasive Ventilation to Prevent Intubation in
Preterm Infants.
AB - BACKGROUND: Noninvasive ventilation is being increasingly used on preterm infants
to reduce ventilator lung injury and bronchopulmonary dysplasia. The aim of this
study was to evaluate the effectiveness of synchronized nasal intermittent
positive pressure ventilation (SNIPPV) to prevent intubation in premature
infants. METHODS: Prospective observational study of SNIPPV use on preterm
infants of less than 32 weeks' gestation. All patients were managed using a
prospective protocol intended to reduce invasive mechanical ventilation (iMV)
use. Previous respiratory status, as well as respiratory outcomes and possible
secondary side effects were analyzed. RESULTS: SNIPPV was used on 78 patients:
electively to support extubation on 25 ventilator-dependent patients and as a
rescue therapy after nasal continuous positive airway pressure failure on 53
patients. For 92% of patients in the elective group and 66% in the rescue group,
iMV was avoided over the following 72 hours. No adverse effects were detected,
and all patients were in a stable condition even if intubation was eventually
needed. CONCLUSIONS: The application of SNIPPV in place of or to remove
mechanical ventilation avoids intubation in 74.4% of preterm infants with
respiratory failure. No adverse effects were detected.
PMID- 27500014
TI - Inadequate Processing of Decellularized Dermal Matrix Reduces Cell Viability In
Vitro and Increases Apoptosis and Acute Inflammation In Vivo.
AB - Decellularized tissue scaffolds are commonly used in the clinic because they can
be used as substitutes for more traditional biomaterials, while imparting
additional physiological effects. Nevertheless, reports of complications
associated with their use are widespread and poorly understood. This study probes
possible causes of these complications by examining cell viability and apoptosis
in response to eluents from decellularized dermis. Using multiple sources of
decellularized dermis, this study shows that typical decellularized scaffolds
(prepared with commonly used laboratory techniques, as well as purchased from
commercial sources) contain soluble components that are cytotoxic and that these
components can be removed by extensive washes in cell culture media. In addition,
this study demonstrates that these observed in vitro phenotypes correlate with
increased apoptosis and acute inflammation when implanted subcutaneously in mice.
PMID- 27500015
TI - Length and Dimensional Measurements at NIST.
AB - This paper discusses the past, present, and future of length and dimensional
measurements at NIST. It covers the evolution of the SI unit of length through
its three definitions and the evolution of NBS-NIST dimensional measurement from
early linescales and gage blocks to a future of atom-based dimensional standards.
Current capabilities include dimensional measurements over a range of fourteen
orders of magnitude. Uncertainties of measurements on different types of material
artifacts range down to 7*10(-8) m at 1 m and 8 picometers (pm) at 300 pm.
Current work deals with a broad range of areas of dimensional metrology. These
include: large-scale coordinate systems; complex form; microform; surface finish;
two-dimensional grids; optical, scanning-electron, atomic-force, and scanning
tunneling microscopies; atomic-scale displacement; and atom-based artifacts.
PMID- 27500016
TI - The Kilogram and Measurements of Mass and Force.
AB - This paper describes the facilities, measurement capabilities, and ongoing
research activities in the areas of mass and force at the National Institute of
Standards and Technology (NIST). The first section of the paper is devoted to
mass metrology and starts with a brief historical perspective on the developments
that led to the current definition of the kilogram. An overview of mass
measurement procedures is given with a brief discussion of current research on
alternative materials for mass standards and surface profiles of the U.S.
national prototype kilograms. A brief outlook into the future possible
redefinition of the unit of mass based on fundamental principles is included. The
second part of this paper focuses on the unit of force and describes the
realization of the unit, measurement procedures, uncertainty in the realized
force, facilities, and current efforts aimed at the realization of small forces.
PMID- 27500017
TI - Primary Atomic Frequency Standards at NIST.
AB - The development of atomic frequency standards at NIST is discussed and three of
the key frequency-standard technologies of the current era are described. For
each of these technologies, the most recent NIST implementation of the particular
type of standard is described in greater detail. The best relative standard
uncertainty achieved to date for a NIST frequency standard is 1.5*10(-15). The
uncertainties of the most recent NIST standards are displayed relative to the
uncertainties of atomic frequency standards of several other countries.
PMID- 27500018
TI - The Ampere and Electrical Standards.
AB - This paper describes some of the major contributions to metrology and physics
made by the NIST Electricity Division, which has existed since 1901. It was one
of the six original divisions of the National Bureau of Standards. The
Electricity Division provides dc and low-frequency calibrations for industrial,
scientific, and research organizations, and conducts research on topics related
to electrical metrology and fundamental constants. The early work of the
Electricity Division staff included the development of precision standards, such
as Rosa and Thomas standard resistors and the ac-dc thermal converter. Research
contributions helped define the early international system of measurement units
and bring about the transition to absolute units based on fundamental principles
and physical and dimensional measurements. NIST research has helped to develop
and refine electrical standards using the quantum Hall effect and the Josephson
effect, which are both based on quantum physics. Four projects covering a number
of voltage and impedance measurements are described in detail. Several other
areas of current research at NIST are described, including the use of the
Internet for international compatibility in metrology, determination of the fine
structure and Planck constants, and construction of the electronic kilogram.
PMID- 27500019
TI - The Kelvin and Temperature Measurements.
AB - The International Temperature Scale of 1990 (ITS-90) is defined from 0.65 K
upwards to the highest temperature measurable by spectral radiation thermometry,
the radiation thermometry being based on the Planck radiation law. When it was
developed, the ITS-90 represented thermodynamic temperatures as closely as
possible. Part I of this paper describes the realization of contact thermometry
up to 1234.93 K, the temperature range in which the ITS-90 is defined in terms of
calibration of thermometers at 15 fixed points and vapor pressure/temperature
relations which are phase equilibrium states of pure substances. The realization
is accomplished by using fixed-point devices, containing samples of the highest
available purity, and suitable temperature-controlled environments. All
components are constructed to achieve the defining equilibrium states of the
samples for the calibration of thermometers. The high quality of the temperature
realization and measurements is well documented. Various research efforts are
described, including research to improve the uncertainty in thermodynamic
temperatures by measuring the velocity of sound in gas up to 800 K, research in
applying noise thermometry techniques, and research on thermocouples. Thermometer
calibration services and high-purity samples and devices suitable for "on-site"
thermometer calibration that are available to the thermometry community are
described. Part II of the paper describes the realization of temperature above
1234.93 K for which the ITS-90 is defined in terms of the calibration of
spectroradiometers using reference blackbody sources that are at the temperature
of the equilibrium liquid-solid phase transition of pure silver, gold, or copper.
The realization of temperature from absolute spectral or total radiometry over
the temperature range from about 60 K to 3000 K is also described. The
dissemination of the temperature scale using radiation thermometry from NIST to
the customer is achieved by calibration of blackbody sources, tungsten-strip
lamps, and pyrometers. As an example of the research efforts in absolute
radiometry, which impacts the NIST spectral irradiance and radiance scales,
results with filter radiometers and a high-temperature blackbody are summarized.
PMID- 27500020
TI - The Candela and Photometric and Radiometric Measurements.
AB - The national measurement system for photometric and radiometric quantities is
presently based upon techniques that make these quantities traceable to a high
accuracy cryogenic radiometer. The redefinition of the candela in 1979 provided
the opportunity for national measurement laboratories to base their photometric
measurements on optical detector technology rather than on the emission from high
temperature blackbody optical sources. The ensuing technical developments of the
past 20 years, including the significant improvements in cryogenic radiometer
performance, have provided the opportunity to place the fundamental maintenance
of photometric quantities upon absolute detector based technology as was allowed
by the 1979 redefinition. Additionally, the development of improved
photodetectors has had a significant impact on the methodology in most of the
radiometric measurement areas. This paper will review the status of the NIST
implementation of the technical changes mandated by the 1979 redefinition of the
candela and its effect upon the maintenance and dissemination of optical
radiation measurements.
PMID- 27500022
TI - In Situ Burning of Oil Spills.
AB - For more than a decade NIST conducted research to understand, measure and predict
the important features of burning oil on water. Results of that research have
been included in nationally recognized guidelines for approval of intentional
burning. NIST measurements and predictions have played a major role in
establishing in situ burning as a primary oil spill response method. Data are
given for pool fire burning rates, smoke yield, smoke particulate size
distribution, smoke aging, and polycyclic aromatic hydrocarbon content of the
smoke for crude and fuel oil fires with effective diameters up to 17.2 m. New
user-friendly software, ALOFT, was developed to quantify the large-scale features
and trajectory of wind blown smoke plumes in the atmosphere and estimate the
ground level smoke particulate concentrations. Predictions using the model were
tested successfully against data from large-scale tests. ALOFT software is being
used by oil spill response teams to help assess the potential impact of
intentional burning.
PMID- 27500021
TI - Materials Research With Neutrons at NIST.
AB - The NIST Materials Science and Engineering Laboratory works with industry,
standards bodies, universities, and other government laboratories to improve the
nation's measurements and standards infrastructure for materials. An increasingly
important component of this effort is carried out at the NIST Center for Neutron
Research (NCNR), at present the most productive center of its kind in the United
States. This article gives a brief historical account of the growth and
activities of the Center with examples of its work in major materials research
areas and describes the key role the Center can expect to play in future
developments.
PMID- 27500023
TI - Statistics and Measurements.
AB - For more than 50 years, the Statistical Engineering Division (SED) has been
instrumental in the success of a broad spectrum of metrology projects at
NBS/NIST. This paper highlights fundamental contributions of NBS/NIST
statisticians to statistics and to measurement science and technology. Published
methods developed by SED staff, especially during the early years, endure as
cornerstones of statistics not only in metrology and standards applications, but
as data-analytic resources used across all disciplines. The history of statistics
at NBS/NIST began with the formation of what is now the SED. Examples from the
first five decades of the SED illustrate the critical role of the division in the
successful resolution of a few of the highly visible, and sometimes
controversial, statistical studies of national importance. A review of the
history of major early publications of the division on statistical methods,
design of experiments, and error analysis and uncertainty is followed by a survey
of several thematic areas. The accompanying examples illustrate the importance of
SED in the history of statistics, measurements and standards: calibration and
measurement assurance, interlaboratory tests, development of measurement methods,
Standard Reference Materials, statistical computing, and dissemination of
measurement technology. A brief look forward sketches the expanding opportunity
and demand for SED statisticians created by current trends in research and
development at NIST.
PMID- 27500024
TI - Mathematics and Measurement.
AB - In this paper we describe the role that mathematics plays in measurement science
at NIST. We first survey the history behind NIST's current work in this area,
starting with the NBS Math Tables project of the 1930s. We then provide examples
of more recent efforts in the application of mathematics to measurement science,
including the solution of ill-posed inverse problems, characterization of the
accuracy of software for micromagnetic modeling, and in the development and
dissemination of mathematical reference data. Finally, we comment on emerging
issues in measurement science to which mathematicians will devote their energies
in coming years.
PMID- 27500025
TI - NIST Mechanisms for Disseminating Measurements.
AB - The national responsibilities assigned to the National Bureau of Standards (NBS)
early in the last century for providing measurement assistance and service are
carried out today by the four programs that comprise the National Institute of
Standards and Technology (NIST) Office of Measurement Services (OMS). They are
the Calibration Program (CP), the Standard Reference Materials Program (SRMP),
the Standard Reference Data Program (SRDP), and the Weights and Measures Program
(W&MP). Organized when the U.S. Congress changed the NBS name to NIST, the OMS
facilitates access to the measurement and standards activities of NIST
laboratories and programs through the dissemination of NIST products, data, and
services. A brief historical introduction followed by a perspective of pivotal
measurement developments from 1901 to the present and concluding with a look to
the future of NIST measurement services in the next decade of the new millennium
are presented for each OMS program.
PMID- 27500026
TI - Information Technology Measurement and Testing Activities at NIST.
AB - Our high technology society continues to rely more and more upon sophisticated
measurements, technical standards, and associated testing activities. This was
true for the industrial society of the 20th century and remains true for the
information society of the 21st century. Over the last half of the 20th century,
information technology (IT) has been a powerful agent of change in almost every
sector of the economy. The complexity and rapidly changing nature of IT have
presented unique technical challenges to the National Institute of Standards and
Technology (NIST) and to the scientific measurement community in developing a
sound measurement and testing infrastructure for IT. This measurement and testing
infrastructure for the important non-physical and non-chemical properties
associated with complex IT systems is still in an early stage of development.
This paper explains key terms and concepts of IT metrology, briefly reviews the
history of the National Bureau of Standards/National Institute of Standards and
Technology (NBS/NIST) in the field of IT, and reviews NIST's current capabilities
and work in measurement and testing for IT. It concludes with a look at what is
likely to occur in the field of IT over the next ten years and what metrology
roles NIST is likely to play.
PMID- 27500027
TI - A Careful Consideration of the Calibration Concept.
AB - This paper presents a detailed discussion of the technical aspects of the
calibration process with emphasis on the definition of the measurand, the
conditions under which the calibration results are valid, and the subsequent use
of the calibration results in measurement uncertainty statements. The concepts of
measurement uncertainty, error, systematic error, and reproducibility are also
addressed as they pertain to the calibration process.
PMID- 27500028
TI - The Development of Fluorescence Intensity Standards.
AB - The use of fluorescence as an analytical technique has been growing over the last
20 years. A major factor in inhibiting more rapid growth has been the inability
to make comparable fluorescence intensity measurements across laboratories. NIST
recognizes the need to develop and provide primary fluorescence intensity
standard (FIS) reference materials to the scientific and technical communities
involved in these assays. The critical component of the effort will be the
cooperation between the Federal laboratories, the manufacturers, and the
technical personnel who will use the fluorescence intensity standards. We realize
that the development and use of FIS will have to overcome many difficulties.
However, as we outline in this article, the development of FIS is feasible.
PMID- 27500029
TI - Concrete Mixing Methods and Concrete Mixers: State of the Art.
AB - As for all materials, the performance of concrete is determined by its
microstructure. Its microstructure is determined by its composition, its curing
conditions, and also by the mixing method and mixer conditions used to process
the concrete. This paper gives an overview of the various types of mixing methods
and concrete mixers commercially available used by the concrete industry. There
are two main types of mixers used: batch mixers and continuous mixers. Batch
mixers are the most common. To determine the mixing method best suited for a
specific application, factors to be considered include: location of the
construction site (distance from the batching plant), the amount of concrete
needed, the construction schedule (volume of concrete needed per hour), and the
cost. Ultimately, the quality of the concrete produced determines its performance
after placement. An important measure of the quality is the homogeneity of the
material after mixing. This paper will review mixing methods in regards to the
quality of the concrete produced. Some procedures used to determine the
effectiveness of the mixing will be examined.
PMID- 27500030
TI - Distribution of Link Distances in a Wireless Network.
AB - The probability distribution is found for the link distance between two randomly
positioned mobile radios in a wireless network for two representative deployment
scenarios: (1) the mobile locations are uniformly distributed over a rectangular
area and (2) the x and y coordinates of the mobile locations have Gaussian
distributions. It is shown that the shapes of the link distance distributions for
these scenarios are very similar when the width of the rectangular area in the
first scenario is taken to be about three times the standard deviation of the
location distribution in the second scenario. Thus the choice of mobile location
distribution is not critical, but can be selected for the convenience of other
aspects of the analysis or simulation of the mobile system.
PMID- 27500031
TI - Information Model for Machine-Tool-Performance Tests.
AB - This report specifies an information model of machine-tool-performance tests in
the EXPRESS [1] language. The information model provides a mechanism for
describing the properties and results of machine-tool-performance tests. The
objective of the information model is a standardized, computer-interpretable
representation that allows for efficient archiving and exchange of performance
test data throughout the life cycle of the machine. The report also demonstrates
the implementation of the information model using three different implementation
methods.
PMID- 27500032
TI - Global and Local Optimization Algorithms for Optimal Signal Set Design.
AB - The problem of choosing an optimal signal set for non-Gaussian detection was
reduced to a smooth inequality constrained mini-max nonlinear programming problem
by Gockenbach and Kearsley. Here we consider the application of several
optimization algorithms, both global and local, to this problem. The most
promising results are obtained when special-purpose sequential quadratic
programming (SQP) algorithms are embedded into stochastic global algorithms.
PMID- 27500033
TI - Video Transmission for Third Generation Wireless Communication Systems.
AB - This paper presents a twin-class unequal protected video transmission system over
wireless channels. Video partitioning based on a separation of the Variable
Length Coded (VLC) Discrete Cosine Transform (DCT) coefficients within each block
is considered for constant bitrate transmission (CBR). In the splitting process
the fraction of bits assigned to each of the two partitions is adjusted according
to the requirements of the unequal error protection scheme employed.
Subsequently, partitioning is applied to the ITU-T H.263 coding standard. As a
transport vehicle, we have considered one of the leading third generation
cellular radio standards known as WCDMA. A dual-priority transmission system is
then invoked on the WCDMA system where the video data, after being broken into
two streams, is unequally protected. We use a very simple error correction coding
scheme for illustration and then propose more sophisticated forms of unequal
protection of the digitized video signals. We show that this strategy results in
a significantly higher quality of the reconstructed video data when it is
transmitted over time-varying multipath fading channels.
PMID- 27500034
TI - Treasure of the Past VI: Standard Potential of the Silver-Silver-Chloride
Electrode from 0 degrees to 95 degrees C and the Thermodynamic Properties of
Dilute Hydrochloric Acid Solutions.
AB - From electromotive-force measurements of the cell without liquid junction:
[Formula: see text]through the range 0 degrees to 95 degrees C, calculations
have been made of (1) the standard potential of the silver-silver-chloride
electrode, (2) the activity coefficient of hydrochloric acid in aqueous solutions
from m (molality) =0 to m=0.1 and from 0 degrees to 90 degrees C, (3) the
relative partial molal heat content of hydrochloric acid, and (4) the relative
partial molal heat capacity of hydrochloric acid. The extrapolations were made by
the method of least squares with the aid of punch-card techniques. Data from at
least 24 cells were analyzed at each temperature, and 81 cells were studied at 25
degrees C. The value of the standard potential was found to be 0.22234 absolute
volt at 25 degrees C, and the standard deviation was 0.02 millivolt at 0 degrees
C, 0.01 millivolt at 25 degrees C, and 0.09 millivolt at 95 degrees C. The
results from 0 degrees to 60 degrees C are compared with earlier determinations
of the standard potential and other quantities derived from the electromotive
force.
PMID- 27500035
TI - Report on the Development of the Advanced Encryption Standard (AES).
AB - In 1997, the National Institute of Standards and Technology (NIST) initiated a
process to select a symmetric-key encryption algorithm to be used to protect
sensitive (unclassified) Federal information in furtherance of NIST's statutory
responsibilities. In 1998, NIST announced the acceptance of 15 candidate
algorithms and requested the assistance of the cryptographic research community
in analyzing the candidates. This analysis included an initial examination of the
security and efficiency characteristics for each algorithm. NIST reviewed the
results of this preliminary research and selected MARS, RCTM, Rijndael, Serpent
and Twofish as finalists. Having reviewed further public analysis of the
finalists, NIST has decided to propose Rijndael as the Advanced Encryption
Standard (AES). The research results and rationale for this selection are
documented in this report.
PMID- 27500036
TI - Photocurrent Measurement of PC and PV HgCdTe Detectors.
AB - Novel preamplifiers for working standard photoconductive (PC) and photovoltaic
(PV) HgCdTe detectors have been developed to maintain the spectral responsivity
scale of the National Institute of Standards and Technology (NIST) in the
wavelength range of 5 MUm to 20 MUm. The linear PC mode preamplifier does not
need any compensating source to zero the effect of the detector bias current for
the preamplifier output. The impedance multiplication concept with a positive
feedback buffer amplifier was analyzed and utilized in a bootstrap PV
transimpedance amplifier to measure photocurrent of a 200 Omega shunt resistance
photodiode with a maximum signal gain of 10(8) V/A. In spite of the high
performance lock-in used as a second-stage signal-amplifier, the signal-to-noise
ratio had to be optimized for the output of the photocurrent preamplifiers. Noise
and drift were equalized for the output of the PV mode preamplifier. The signal
gain errors were calculated to determine the signal frequency range where
photocurrent-to-voltage conversion can be performed with very low uncertainties.
For the design of both PC and PV detector preamplifiers, the most important gain
equations are described. Measurement results on signal ranges and noise
performance are discussed.
PMID- 27500037
TI - Treasure of the Past VII: Measurement of the Thickness and Refractive Index of
Very Thin Films and the Optical Properties of Surfaces by Ellipsometry.
AB - The use of the ellipsometer for the measurement of the thickness and refractive
index of very thin films is reviewed. The Poincare sphere representation of the
state of polarization of light is developed and used to describe the reflection
process. Details of the operation of the ellipsometer are examined critically. A
computational method is presented by which the thickness of a film of known
refractive index on a reflecting substrate of known optical constants may be
calculated directly from the ellipsometer readings. A method for computing both
the refractive index and thickness of an unknown film is also developed. These
methods have been applied to the determination of the thickness of an adsorbed
water layer on chromium ferrotype plates and on gold surfaces. In the former case
the thickness was 23 to 27 A, and in the latter was 2 to 5 A. The measurement of
the thickness and refractive index of barium fluoride films evaporated on
chromium ferrotype surfaces is used as an illustration of the simultaneous
determination of these two quantities.
PMID- 27500038
TI - WORKSHOP ON TEXTURE IN ELECTRONIC APPLICATIONS Gaithersburg, MD October 10-11,
2000.
PMID- 27500039
TI - Hysteresis and Related Error Mechanisms in the NIST Watt Balance Experiment.
AB - The NIST watt balance experiment is being completely rebuilt after its 1998
determination of the Planck constant. That measurement yielded a result with an
approximately 1*10(-7) relative standard uncertainty. Because the goal of the new
incarnation of the experiment is a ten-fold decrease in uncertainty, it has been
necessary to reexamine many sources of systematic error. Hysteresis effects
account for a substantial portion of the projected uncertainty budget. They arise
from mechanical, magnetic, and thermal sources. The new experiment incorporates
several improvements in the apparatus to address these issues, including stiffer
components for transferring the mass standard on and off the balance, better
servo control of the balance, better pivot materials, and the incorporation of
erasing techniques into the mass transfer servo system. We have carried out a
series of tests of hysteresis sources on a separate system, and apply their
results to the watt apparatus. The studies presented here suggest that our
improvements can be expected to reduce hysteresis signals by at least a factor of
10-perhaps as much as a factor of 50-over the 1998 experiment.
PMID- 27500040
TI - Comparison of Two Cryogenic Radiometers at NIST.
AB - Two cryogenic radiometers from NIST, one from the Optical Technology Division and
the other from the Optoelectronics Division, were compared at three visible laser
wavelengths. For this comparison, each radiometer calibrated two photodiode trap
detectors for spectral responsivity. The calibration values for the two trap
detectors agreed within the expanded (k = 2) uncertainties. This paper describes
the measurement and results of this comparison.
PMID- 27500041
TI - Sources of Error in UV Radiation Measurements.
AB - Increasing commercial, scientific, and technical applications involving
ultraviolet (UV) radiation have led to the demand for improved understanding of
the performance of instrumentation used to measure this radiation. There has been
an effort by manufacturers of UV measuring devices (meters) to produce simple,
optically filtered sensor systems to accomplish the varied measurement needs. We
address common sources of measurement errors using these meters. The uncertainty
in the calibration of the instrument depends on the response of the UV meter to
the spectrum of the sources used and its similarity to the spectrum of the
quantity to be measured. In addition, large errors can occur due to out-of-band,
non-linear, and non-ideal geometric or spatial response of the UV meters.
Finally, in many applications, how well the response of the UV meter approximates
the presumed action spectrum needs to be understood for optimal use of the
meters.
PMID- 27500042
TI - Hysteresis in Transport Critical-Current Measurements of Oxide Superconductors.
AB - We have investigated magnetic hysteresis in transport critical-current (I c)
measurements of Ag-matrix (Bi,Pb)2Sr2Ca2Cu3O10- x (Bi-2223) and AgMg-matrix
Bi2Sr2CaCu2O8+ x (Bi-2212) tapes. The effect of magnetic hysteresis on the
measured critical current of high temperature superconductors is a very important
consideration for every measurement procedure that involves more than one sweep
of magnetic field, changes in field angle, or changes in temperature at a given
field. The existence of this hysteresis is well known; however, the implications
for a measurement standard or interlaboratory comparisons are often ignored and
the measurements are often made in the most expedient way. A key finding is that
I c at a given angle, determined by sweeping the angles in a given magnetic
field, can be 17 % different from the I c determined after the angle was fixed in
zero field and the magnet then ramped to the given field. Which value is correct
is addressed in the context that the proper sequence of measurement conditions
reflects the application conditions. The hysteresis in angle-sweep and
temperature-sweep data is related to the hysteresis observed when the field is
swept up and down at constant angle and temperature. The necessity of heating a
specimen to near its transition temperature to reset it to an initial state
between measurements at different angles and temperatures is discussed.
PMID- 27500043
TI - Powder X-Ray Reference Patterns of Sr2RGaCu2O y (R = Pr, Nd, Sm, Eu, Gd, Dy, Ho,
Er, Tm, and Y).
AB - X-Ray Rietveld refinements were conducted on a series of eleven lanthanide
phases, Sr2RGaCu2O y (2112 phase, R = Pr, Nd, Sm, Eu, Gd, Dy, Ho, Y, Er, Tm, and
Yb) that are structurally related to the high T c superconductor Ba2YCu3O7 (213).
In the 2112 structure, instead of square planar Cu-O chains, tetrahedral GaO4
chains were found to run in a zig-zag fashion along the diagonal of the basal 213
ab-direction. Reference powder patterns for these compounds were prepared by
using the Rietveld decomposition technique. The unit cell volume of these
compounds follows the expected trend of the lanthanide contraction. The lattice
parameters range from a = 22.9694(3) A, b = 5.5587(2) A, and c = 5.44743(7) A for
R = Pr, to a = 22.8059(2) A, b = 5.46031(5) A, and c = 5.37773(5) A for R = Yb.
An electon diffraction study of the Sm- and Er-analogs showed characteristic
diffuse streaks along the b-axis, suggesting some disorder within the GaO4
chains.
PMID- 27500044
TI - Compressing Spin-Polarized (3)He With a Modified Diaphragm Pump.
AB - Nuclear spin-polarized (3)He gas at pressures on the order of 100 kPa (1 bar) are
required for several applications, such as neutron spin filters and magnetic
resonance imaging. The metastability-exchange optical pumping (MEOP) method for
polarizing (3)He gas can rapidly produce highly polarized gas, but the best
results are obtained at much lower pressure (~0.1 kPa). We describe a compact
compression apparatus for polarized gas that is based on a modified commercial
diaphragm pump. The gas is polarized by MEOP at a typical pressure of 0.25 kPa
(2.5 mbar), and compressed into a storage cell at a typical pressure of 100 kPa.
In the storage cell, we have obtained 20 % to 35 % (3)He polarization using pure
(3)He gas and 35 % to 50 % (3)He polarization using (3)He-(4)He mixtures. By
maintaining the storage cell at liquid nitrogen temperature during compression,
the density has been increased by a factor of four.
PMID- 27500046
TI - Fraunhofer Diffraction Effects on Total Power for a Planckian Source.
AB - An algorithm for computing diffraction effects on total power in the case of
Fraunhofer diffraction by a circular lens or aperture is derived. The result for
Fraunhofer diffraction of monochromatic radiation is well known, and this work
reports the result for radiation from a Planckian source. The result obtained is
valid at all temperatures.
PMID- 27500045
TI - Treasure of the Past VIII: Molecular Basis of Flame Inhibition.
AB - The role played by inorganic chemical additives in fire retardancy and flame
inhibition is considered. Particular attention is given to the molecular level
aspects of commercially important systems containing compounds of antimony,
halogens, and phosphorus. The flame inhibiting function of metal containing
additives is also discussed.
PMID- 27500047
TI - Environmental Radiation Monitoring at NBS/NIST From 1960 Through 2000.
AB - The program for monitoring the environment in and about the site of the National
Bureau of Standards, now the National Institute of Standards and Technology, at
its Gaithersburg, Maryland location began in 1960. The program includes
measurements of radiation fields at the fence line of the site and of
radionuclides in samples of soil, water, and biota taken within and around the
site. A variety of instruments and equipment, processes and procedures, and
measurement devices has been employed. To date, no measurement from the routine
program has exhibited any result that could be attributed to any effluent or
other effect of the radiological work conducted at the site; that includes the
NIST Research Reactor, the now defunct Linear Electron Accelerator (LINAC) and
other accelerators, radiochemistry, and sealed source operations.
PMID- 27500048
TI - Vibrational Branching Ratios and Asymmetry Parameters in the Photoionization of
CO2 in the Region Between 650 A and 840 A.
AB - The vibrational branching ratios and asymmetry parameters for CO2 have been
determined in the wavelength region of 650 A to near the ionization onset at
about 840 A. The study was performed using synchrotron radiation from the
Daresbury storage ring that was dispersed with a 5 m grating monochomator that
afforded resolution of 0.1 A to 0.2 A. This resolution allowed the study of the
branching ratios and asymmetry parameters with enough detail to see the changes
in the parameters within the pronounced autoionization structure in CO2 in this
wavelength region. While the electron spectrometer resolution was not sufficient
to resolve the spin orbit and Renner-Teller splitting in the photoelectron
spectra, we are able to fit the data with a model that identifies the major
structure in terms of the symmetric stretch and elements of the asymmetric
stretch and bending modes. A calculation of the expected relative vibrational
excitations based upon the Franck-Condon principle clearly showed non-Franck
Condon behavior in some of the vibrational-electronic transitions.
PMID- 27500049
TI - Transfer Calibration Validation Tests on a Heat Flux Sensor in the 51 mm High
Temperature Blackbody.
AB - Facilities and techniques to characterize heat flux sensors are under development
at the National Institute of Standards and Technology. As a part of this effort,
a large aperture high-temperature blackbody was commissioned recently. The
graphite tube blackbody, heated electrically, has a cavity diameter of 51 mm and
can operate up to a maximum temperature of 2773 K. A closed-loop cooling system
using a water-to-water heat exchanger cools electrodes and the outer reflecting
shield. This paper describes the newly developed blackbody facility and the
validation tests conducted using a reference standard Schmidt-Boelter heat flux
sensor. The transfer calibration results obtained on the Schmidt-Boelter sensor
agreed with the previous data within the experimental uncertainty limits.
PMID- 27500050
TI - Precision Ultrasonic Wave Measurements With Simple Equipment.
AB - We describe the design and construction of a relatively simple, inexpensive laser
interferometer system for accurate measurements of ultrasonic surface
displacement waveforms in reasonably friendly environments. We show how analysis
of a single waveform can provide both the calibration constant required for
absolute measurements and an estimate of the uncertainty of these measurements.
We demonstrate the performance of this interferometer by measuring ultrasonic
waveforms generated by a novel conical-element ultrasonic transducer.
PMID- 27500051
TI - Studies of Excess Heat and Convection in a Water Calorimeter.
AB - To explain a difference of 0.5 % between the absorbed-dose standards of the
National Institute of Standards and Technology (NIST) and the National Research
Council of Canada (NRCC), Seuntjens et al. suggest the fault lies with the NIST
water calorimeter being operated at 22 degrees C and the method with which the
measurements were made. Their calculations show that this difference is due to
overprediction of temperature rises of six consecutive (60)Co radiation runs at
NIST. However, the consecutive runs they refer to were merely preliminary
measurements to determine the procedure for the NIST beam calibration. The beam
calibration was determined from only two consecutive runs followed by water
circulation to re-establish temperature equilibrium. This procedure was used for
measurements on 77 days, with 32 runs per day. Convection external to the glass
cylindrical detector assembly performed a beneficial role. It aided (along with
conduction) in increasing the rate of excess heat transported away from the thin
cylindrical wall. This decreased the rate of heat conducted toward the axially
located thermistors. The other sources of excess heat are the: (1) non-water
materials in the temperature probe, and (2) exothermic effect of the once
distilled water external to the cylinder. Finite-element calculations were made
to determine the separate and combined effects of the excess heat sources for the
afterdrift. From this analysis, extrapolation of the measured afterdrifts of two
consecutive runs to mid radiation leads to an estimated over-prediction of no
more than about 0.1 %. Experimental measurements contradict the calculated
results of Seuntjens et al. that convective motion (a plume) originates from the
thermistors operated with an electrical power dissipation as low as 0.6 MUW, well
below the measured threshold of 50 MUW. The method used for detecting a plume was
sensitive enough to measure a convective plume (if it had started) down to about
the 10 MUW power level. Measurements also contradict the NRCC calculations in
predicting the behavior of the NIST afterdrifts.
PMID- 27500052
TI - Treasure of the Past IX: Exposure Standardization of Iodine-125 Seeds Used for
Brachytherapy.
AB - A method for calibrating iodine-125 seeds in terms of exposure has been
established. The standard free-air ionization chamber, used for measuring soft x
rays, was chosen for the measurements. Arrays of four to six seeds were used to
enhance the ionization-current-to-background-current ratio. Seeds from an array
were measured individually in a re-entrant chamber. The quotient of the exposure
rate for the array by the sum of the ionization currents in the re-entrant
chamber is the calibration factor for the re-entrant chamber. Calibration factors
were established for three types of iodine-125 seeds. The overall uncertainty for
the seed exposure calibrations is less than 6%.
PMID- 27500053
TI - NIST-ASME WORKSHOP ON UNCERTAINTY IN DIMENSIONAL MEASUREMENTS Gaithersburg, MD
June 5-7, 2001.
PMID- 27500054
TI - High Pressure X-Ray Crystallography With the Diamond Cell at NIST/NBS.
AB - Scientists in the Crystallography Section at NIST/NBS made several outstanding
contributions which greatly promoted the development and advancement of high
pressure x-ray crystallography during the second-half of the 20th century. These
milestone achievements or "firsts" included: (1) the invention of the lever-arm
type diamond anvil cell (DAC) in 1958; (2) the development of DAC technology for
powder x-ray diffraction at high pressure in 1960; (3) the introduction of DAC
methodology for single crystal x-ray diffraction at high pressure in 1964; (4)
the invention of the optical fluorescence ruby method of pressure measurement in
1971; and (5) the discovery of hydrostatic pressure-transmitting media useful to
unprecedented pressures for that time. These achievements provided the spark that
ignited the explosion of activity in high pressure research that occurred in
laboratories throughout the world during the latter part of the 20th century. It
is still going on, unabated, today. An estimated 5000 DACs were built during the
last 40 years.
PMID- 27500055
TI - Past and Present Crystallographic Work at the NBS/NIST Reactor.
AB - Neutron diffraction at NBS/NIST started soon after the NBS reactor became
operational in the summer of 1969. Since that time, literally hundreds of crystal
structures have been determined and refined using single crystal and powder
neutron diffraction data, collected with a variety of instruments. This work has
been usually done in collaboration with other NBS/NIST divisions and/or
universities and industrial laboratories. In parallel with the technical
developments and the experimental work, also theoretical aspects of crystal
geometry have been clarified, and significant improvements in the techniques of
profile refinements have been made. It is therefore understandable that a
comprehensive description of all the crystallographic studies carried out up to
the present is impossible under the constraints of space and time imposed by a
review of this type, and, in the following sections, we will limit ourselves to
give, only a brief account of the topics which, in our opinion, represent the
highlights of the work carried out at the reactor.
PMID- 27500057
TI - Investigations of Zeolitic Materials at the NIST Center for Neutron Research.
AB - Crystallographic studies of four zeolitic materials using neutron powder
diffraction data are presented. In most cases, these projects benefited from the
combined use of neutron and x-ray measurements.
PMID- 27500056
TI - Magnetic Structure Determinations at NBS/NIST.
AB - Magnetic neutron scattering plays a central role in determining and understanding
the microscopic properties of a vast variety of magnetic systems, from the
fundamental nature, symmetry, and dynamics of magnetically ordered materials to
elucidating the magnetic characteristics essential in technological applications.
From the early days of neutron scattering measurements at NBS/NIST, magnetic
diffraction studies have been a central theme involving many universities,
industrial and government labs from around the United States and worldwide. Such
measurements have been used to determine the spatial arrangement and directions
of the atomic magnetic moments, the atomic magnetization density of the
individual atoms in the material, and the value of the ordered moments as a
function of thermodynamic parameters such as temperature, pressure, and applied
magnetic field. These types of measurements have been carried out on single
crystals, powders, thin films, and artificially grown multilayers, and often the
information collected can be obtained by no other experimental technique. This
article presents, in an historical perspective, a few examples of work carried
out at the NIST Center for Neutron Research (NCNR), and discusses the key role
that the Center can expect to play in future magnetism research.
PMID- 27500058
TI - Quasicrystals.
AB - The discretely diffracting aperiodic crystals termed quasicrystals, discovered at
NBS in the early 1980s, have led to much interdisciplinary activity involving
mainly materials science, physics, mathematics, and crystallography. It led to a
new understanding of how atoms can arrange themselves, the role of periodicity in
nature, and has created a new branch of crystallography.
PMID- 27500059
TI - Lattice Symmetry and Identification-The Fundamental Role of Reduced Cells in
Materials Characterization.
AB - In theory, physical crystals can be represented by idealized mathematical
lattices. Under appropriate conditions, these representations can be used for a
variety of purposes such as identifying, classifying, and understanding the
physical properties of materials. Critical to these applications is the ability
to construct a unique representation of the lattice. The vital link that enabled
this theory to be realized in practice was provided by the 1970 paper on the
determination of reduced cells. This seminal paper led to a mathematical approach
to lattice analysis initially based on systematic reduction procedures and the
use of standard cells. Subsequently, the process evolved to a matrix approach
based on group theory and linear algebra that offered a more abstract and
powerful way to look at lattices and their properties. Application of the reduced
cell to both database work and laboratory research at NIST was immediately
successful. Currently, this cell and/or procedures based on reduction are widely
and routinely used by the general scientific community: (i) for calculating
standard cells for the reporting of crystalline materials, (ii) for classifying
materials, (iii) in crystallographic database work (iv) in routine x-ray and
neutron diffractometry, and (v) in general crystallographic research. Especially
important is its use in symmetry determination and in identification. The focus
herein is on the role of the reduced cell in lattice symmetry determination.
PMID- 27500060
TI - Electron Diffraction Using Transmission Electron Microscopy.
AB - Electron diffraction via the transmission electron microscope is a powerful
method for characterizing the structure of materials, including perfect crystals
and defect structures. The advantages of electron diffraction over other methods,
e.g., x-ray or neutron, arise from the extremely short wavelength (~2 pm), the
strong atomic scattering, and the ability to examine tiny volumes of matter (~10
nm(3)). The NIST Materials Science and Engineering Laboratory has a history of
discovery and characterization of new structures through electron diffraction,
alone or in combination with other diffraction methods. This paper provides a
survey of some of this work enabled through electron microscopy.
PMID- 27500061
TI - JCPDS-ICDD Research Associateship (Cooperative Program with NBS/NIST).
AB - The Research Associateship program of the Joint Committee on Powder Diffraction
International Centre for Diffraction Data (JCPDS-ICDD, now known as the ICDD) at
NBS/NIST was a long standing (over 35 years) successful industry-government
cooperation. The main mission of the Associateship was to publish high quality x
ray reference patterns to be included in the Powder Diffraction File (PDF). The
PDF is a continuing compilation of patterns gathered from many sources, compiled
and published by the ICDD. As a result of this collaboration, more than 1500 high
quality powder diffraction patterns, which have had a significant impact on the
scientific community, were reported. In addition, various research collaborations
with NBS/NIST also led to the development of several standard reference materials
(SRMs) for instrument calibration and quantitative analyses, and computer
software for data collection, calibration, reduction, for the editorial process
of powder pattern publication, analysis of powder data, and for quantitative
analyses. This article summarizes information concerning the JCPDS-ICDD
organization, the Powder Diffraction File (PDF), history and accomplishments of
the JCPDS-ICDD Research Associateship.
PMID- 27500062
TI - A Natural Bone Cement-A Laboratory Novelty Led to the Development of
Revolutionary New Biomaterials.
AB - Research on calcium phosphate chemistry at NIST led to the discovery of the
worlds first self-hardening calcium phosphate cements (CPC) in 1987. Laboratory,
animal, and clinical studies were conducted to develop CPC into clinically useful
biomaterials. The combination of self-hardening capability and high
biocompatibility makes CPC a unique material for repairing bone defects. Near
perfect adaptation of the cement to the tissue surfaces in a defect, and a
gradual resorption followed by new bone formation are some of the other
distinctive advantages of this biomaterial. In 1996 a CPC, consisting of
tetracalcium phosphate and dicalcium phosphate anhydrous, was approved by the
Food and Drug Administration (FDA) for repairing cranial defects in humans, thus
becoming the first material of its kind available for clinical use. This paper
will review the course of the development, the physical and chemical properties,
and clinical applications of CPC.
PMID- 27500063
TI - Structures of Biological Minerals in Dental Research.
AB - Structural features of some calcium phosphates of biological interest are
described. Structure of hydroxyapatite (OHAp), considered as the prototype for
the inorganic component of bones and teeth is discussed with respect to the kinds
and locations of ionic substitutions. Octacalcium phosphate (OCP), is a probable
precursor in biological mineralization. OCP has a layer type structure, with one
layer quite similar to that of OHAp and the other, a hydrated layer consisting of
more widely spaced Ca, and PO4 ions and the water molecules. The closeness of fit
in the apatitic layers of OCP and OHAp accounts for the epitaxial, interlayered
mixtures formed by these compounds and the in situ conversion of OCP to OHAp.
Possible roles of OCP in biological mineralization are discussed.
PMID- 27500064
TI - NIST Materials Properties Databases for Advanced Ceramics.
AB - The NIST Ceramics Division maintains two databases on the physical, mechanical,
thermal, and other properties of high temperature superconductors and structural
ceramics. Crystallographic data are featured prominently among the physical
property data and serve several important functions in the classification and
evaluation of the property values. The scope of materials, properties, and data
evaluation protocols are discussed for the two databases.
PMID- 27500065
TI - Contributions of NIST/NBS Researchers to the Crystallography of Construction
Materials.
AB - For more than 100 years, the primary theme underlying the NBS/NIST staff
contribution to the crystallography of building materials has been the
development of an improved understanding of concrete materials performance. Over
that time period, portland cement concrete has become one of the most important
of our construction materials for roads, buildings, and other large municipal
structures. At the beginning of the 20th century our understanding of portland
cement composition, performance, use in concrete, and how the concrete performs
in harsh environments was lacking. The efforts of NIST have served to advance
construction materials science and technology through the combined efforts of
experimental, field study, and theoretical computational materials science. One
major achievement in the late 1920s, derived from studies on phase equilibria in
cement clinker, allows calculation of potential cement clinker composition. Known
as the Bogue calculation, this continues to be an essential tool in cement plant
process control to this day. Additionally, contributions of NIST scientists to
our knowledge of the chemistry and nature of cement hydration products have been
crucial in our understanding of cement hydration and concrete durability. Today,
computational materials science is a rapidly developing discipline, and NIST is
developing tools incorporating predictive models aided by empirical studies.
Examples include a computer-integrated knowledge system for prediction and
optimization of performance and life-cycle cost of high performance concrete and
the Virtual Cement and Concrete Testing Laboratory. Understanding the
relationships between material and performance properties has not been confined
only to portland cements. One of the longest running experiments at NIST, the
stone test wall, has stood for over 50 years as one of the world's largest single
collections of building stone, and is invaluable for studying weathering effects
associated with stone mineralogy and texture. Standards development has also been
promoted through participation on ASTM subcommittees on stone, cement, and
concrete. The Cement and Concrete Reference Laboratory, established in 1929,
continues to provide testing and training for outside laboratories and maintains
a historical record of test data on construction materials.
PMID- 27500066
TI - Crystallographic Texture in Ceramics and Metals.
AB - Preferred crystallographic orientation, or texture, occurs almost universally,
both in natural and man-made systems. Many components and devices in electronic
and magnetic systems are fabricated from materials that have crystallographic
texture. With the rapidly increasing use of thin film technology, where sharp
axisymmetric crystallographic texture normal to the film plane is frequently
observed, the occurrence and impact of texture are rising. Thin film applications
in which the texture of the material plays a key role in determining properties
and performance are broad: complex oxides in random access memory devices, ZnO
thin film resonators for cell phone applications, metallic alloys in magnetic
recording media, and Al and Cu interconnects in integrated circuits are but a few
examples. Texture is established during the synthesis or post-synthesis heat
treatment of a material and thus has a strong dependence upon processing history.
Accurate measurement of texture is not simple and a variety of tools and
approaches are being actively employed in texture studies. X-ray, neutron and
electron diffraction based techniques are practiced around the world at varying
levels of complexity with regard to equipment and analysis methods. Despite the
well-documented existence of these varied approaches, many reported texture
measurements on electronic materials are based solely on the relative intensities
of conventional theta-2theta x-ray diffraction peaks, which typically yield
inaccurate results. NIST has developed quantitative texture measurement
techniques that employ equipment commonly available in most industrial and
academic settings. A number of examples of texture measurement in ceramic and
metal systems will be presented, taken from the historical development and
application of these techniques at NIST over the past 7 years.
PMID- 27500067
TI - Standard Reference Material (SRM 1990) For Single Crystal Diffractometer
Alignment.
AB - An international project was successfully completed which involved two major
undertakings: (1) a round-robin to demonstrate the viability of the selected
standard and (2) the certification of the lattice parameters of the SRM 1990, a
Standard Reference Material((r)) for single crystal diffractometer alignment.
This SRM is a set of ~3500 units of Cr-doped Al2O3, or ruby spheres [(0.420.011
mole fraction % Cr (expanded uncertainty)]. The round-robin consisted of
determination of lattice parameters of a pair of crystals: the ruby sphere as a
standard, and a zeolite reference to serve as an unknown. Fifty pairs of crystals
were dispatched from Hauptman-Woodward Medical Research Institute to volunteers
in x-ray laboratories world-wide. A total of 45 sets of data was received from 32
laboratories. The mean unit cell parameters of the ruby spheres was found to be
a=4.7608 A+/-0.0062 A, and c=12.9979 A+/-0.020 A (95 % intervals of the
laboratory means). The source of errors of outlier data was identified. The SRM
project involved the certification of lattice parameters using four well-aligned
single crystal diffractometers at (Bell Laboratories) Lucent Technologies and at
NRC of Canada (39 ruby spheres), the quantification of the Cr content using a
combined microprobe and SEM/EDS technique, and the evaluation of the mosaicity of
the ruby spheres using a double-crystal spectrometry method. A confirmation of
the lattice parameters was also conducted using a Guinier-Hagg camera. Systematic
corrections of thermal expansion and refraction corrections were applied. These
rubies- are rhombohedral, with space group [Formula: see text]. The certified
mean unit cell parameters are a=4.76080+/-0.00029 A, and c=12.99568 A+/-0.00087 A
(expanded uncertainty). These certified lattice parameters fall well within the
results of those obtained from the international round-robin study. The Guinier
Hagg transmission measurements on five samples of powdered rubies (a=4.7610 A+/
0.0013 A, and c = 12.9954 A+/-0.0034 A) agreed well with the values obtained from
the single crystal spheres.
PMID- 27500068
TI - Phase Equilibria and Crystallography of Ceramic Oxides.
AB - Research in phase equilibria and crystallography has been a tradition in the
Ceramics Division at National Bureau of Standards/National Institute of
Standatrds and Technology (NBS/NIST) since the early thirties. In the early
years, effort was concentrated in areas of Portland cement, ceramic glazes and
glasses, instrument bearings, and battery materials. In the past 40 years, a
large portion of the work was related to electronic materials, including
ferroelectrics, piezoelectrics, ionic conductors, dielectrics, microwave
dielectrics, and high-temperature superconductors. As a result of the phase
equilibria studies, many new compounds have been discovered. Some of these
discoveries have had a significant impact on US industry. Structure
determinations of these new phases have often been carried out as a joint effort
among NBS/NIST colleagues and also with outside collaborators using both single
crystal and neutron and x-ray powder diffraction techniques. All phase equilibria
diagrams were included in Phase Diagrams for Ceramists, which are collaborative
publications between The American Ceramic Society (ACerS) and NBS/NIST. All x-ray
powder diffraction patterns have been included in the Powder Diffraction File
(PDF). This article gives a brief account of the history of the development of
the phase equilibria and crystallographic research on ceramic oxides in the
Ceramics Division. Represented systems, particularly electronic materials, are
highlighted.
PMID- 27500069
TI - Towards Near Perfect Crystals With Only Well-Characterized Imperfections.
AB - Throughout the past century NBS/NIST supported a great variety of research
studies in crystallography where the aim was the highest attainable accuracy in
measurements. While avoiding overlap with other papers in this volume, this
article summarizes results from: 1) early work on crystallization as a method of
purification, in contributions to sugar chemistry, and in solution growth of
large crystals; 2) the NBS/ARPA Program of research on crystal growth and
characterization; 3) the NBS Free-Radical Research Program; 4) the XRCD method as
a direct path to relative atomic mass data and the fundamental physical
constants; 5) the dynamical theory of x-ray diffraction; and 6) symmetry
considerations such as are involved in the influence on crystals of mechanical
stress or fields, and of point defect motion.
PMID- 27500070
TI - National Institute of Standards and Technology Synchrotron Radiation Facilities
for Materials Science.
AB - Synchrotron Radiation Facilities, supported by the Materials Science and
Engineering Laboratory of the National Institute of Standards and Technology,
include beam stations at the National Synchrotron Light Source at Brookhaven
National Laboratory and at the Advanced Photon Source at Argonne National
Laboratory. The emphasis is on materials characterization at the microstructural
and at the atomic and molecular levels, where NIST scientists, and researchers
from industry, universities and government laboratories perform state-of-the-art
x-ray measurements on a broad range of materials.
PMID- 27500071
TI - Macromolecular Crystallography and Structural Biology Databases at NIST.
AB - In the late 1970s, macromolecular crystallography at NIST began with
collaboration between NIST and NIH to establish a single-crystal neutron
diffractometer. This instrument was constructed and employed to solve a number of
crystal structures: bovine ribonuclease A, bovine-ribonuclease-uridine vanadate
complex, and porcine insulin. In the mid 1980s a Biomolecular Structure Group was
created establishing NIST capabilities in biomolecular singe-crystal x-ray
diffraction. The group worked on a variety of structural problems until joining
the NIST/UMBI Center for Advanced Research in Biotechnology (CARB) in 1987.
Crystallographic studies at CARB were then focused on protein engineering efforts
that included among others chymosin, subtilisin BPN', interleukin 1beta, and
glutathione S-transferase. Recently, the structural biology efforts have centered
on enzymes in the chorismate metabolic pathways involved in amino acid
biosynthesis and in structural genomics that involves determining the structures
of "hypothetical" proteins to aid in assigning function. In addition to
crystallographic studies, structural biology database activities began with the
formal establishment of the Biological Macro-molecule Crystallization Database in
1989. Later, in 1997, NIST in partnership with Rutgers and UCSD formed the
Research Collaboratory for Structural Bioinformatics that successfully acquired
the Protein Data Bank. The NIST efforts in these activities have focused on data
uniformity, establishing and maintaining the physical archive, and working with
the NMR community.
PMID- 27500072
TI - EAST syndrome: Clinical, pathophysiological, and genetic aspects of mutations in
KCNJ10.
AB - EAST syndrome is a recently described autosomal recessive disorder secondary to
mutations in KCNJ10 (Kir4.1), a gene encoding a potassium channel expressed in
the brain, eye, ear and kidney. This condition is characterized by 4 cardinal
features; Epilepsy, Ataxia, Sensorineural deafness, and (a renal salt-wasting)
Tubulopathy, hence the acronym EAST syndrome. Here we review reported clinical
manifestations, in particular the neurological signs and symptoms which typically
have the most impact on the quality of life of patients. In addition we review
the pathophysiology and genetic aspects of the disease. So far 14 different
KCNJ10 mutations have been published which either directly affect channel
function or may lead to mislocalisation. Investigations of the pathophysiology
may provide clues to potential treatments.
PMID- 27500073
TI - SDF1-CXCR4 signaling: A new player involved in DiGeorge/22q11-deletion syndrome.
AB - The DiGeorge/22q11-deletion syndrome (22q11DS), also known as velocardiofacial
syndrome, is a congenital disease causing numerous structural and behavioral
disorders, including cardiac outflow tract anomalies, craniofacial
dysmorphogenesis, parathyroid and thymus hypoplasia, and mental disorders. It
results from a unique chromosomal microdeletion on the 22q11.2 region in which
the transcriptional activator TBX1 is decisive for the occurrence of the disease.
During embryogenesis, Tbx1 is required for patterning of pharyngeal region giving
rise to structures of the face, neck and chest. Genetic and developmental studies
demonstrated that the severity and variability of the syndrome are determined by
Tbx1 targets involved in pharyngeal neural crest cell migration and survival.
Recently, we demonstrated that the chemokine Sdf1/Cxcl12 and its receptor Cxcr4
are genetically downstream of Tbx1 during pharyngeal development and that
reduction of CXCR4 signaling results in defects which recapitulate the major
morphological anomalies of 22q11DS, supporting the possibility of a pivotal role
for the SDF1/CXCR4 axis in its etiology.
PMID- 27500075
TI - Prosocial Behavior Mitigates the Negative Effects of Stress in Everyday Life.
AB - Recent theories of stress reactivity posit that, when stressed, individuals tend
to seek out opportunities to affiliate with and nurture others in order to
prevent or mitigate the negative effects of stress. However, few studies have
tested empirically the role of prosocial behavior in reducing negative emotional
responses to stress. The current analyses used daily diary data to investigate
whether engaging in prosocial behavior buffered the negative effects of naturally
occurring stressors on emotional well-being. Results showed that on a given day,
prosocial behavior moderated the effects of stress on positive affect, negative
affect, and overall mental health. Findings suggest that affiliative behavior may
be an important component of coping with stress, and indicate that engaging in
prosocial behavior might be an effective strategy for reducing the impact of
stress on emotional functioning.
PMID- 27500074
TI - Pathological relationships involving iron and myelin may constitute a shared
mechanism linking various rare and common brain diseases.
AB - We previously demonstrated elevated brain iron levels in myelinated structures
and associated cells in a hemochromatosis Hfe (-/-) xTfr2 (mut) mouse model. This
was accompanied by altered expression of a group of myelin-related genes,
including a suite of genes causatively linked to the rare disease family
'neurodegeneration with brain iron accumulation' (NBIA). Expanded data mining and
ontological analyses have now identified additional myelin-related transcriptome
changes in response to brain iron loading. Concordance between the mouse
transcriptome changes and human myelin-related gene expression networks in normal
and NBIA basal ganglia testifies to potential clinical relevance. These analyses
implicate, among others, genes linked to various rare central hypomyelinating
leukodystrophies and peripheral neuropathies including Pelizaeus-Merzbacher-like
disease and Charcot-Marie-Tooth disease as well as genes linked to other rare
neurological diseases such as Niemann-Pick disease. The findings may help
understand interrelationships of iron and myelin in more common conditions such
as hemochromatosis, multiple sclerosis and various psychiatric disorders.
PMID- 27500076
TI - Measuring Capacity for Resilience among Coastal Counties of the US Northern Gulf
of Mexico Region.
AB - Many have voiced concern about the long-term survival of coastal communities in
the face of increasingly intense storms and sea level rise. In this study we
select indicators of key theoretical concepts from the social-ecological
resilience literature, aggregate those indicators into a resilience-capacity
index, and calculate an index score for each of the 52 coastal counties of
Louisiana, Texas, Mississippi, Alabama and Florida. Building upon Cutter's Social
Vulnerability Index work [1], we use Factor Analysis to combine 43 variables
measuring demographics, social capital, economic resources, local government
actions, and environmental conditions within the counties. Then, we map the
counties' scores to show the spatial distribution of resilience capacities. The
counties identified as having the highest resilience capacities include the
suburban areas near New Orleans, Louisiana and Tampa, Florida, and the growing
beach-tourist communities of Alabama and central Florida. Also, we examine
whether those counties more active in oil and gas development and production,
part of the region's "energy coast", have greater capacity for resilience than
other counties in the region. Correlation analyses between the resilience
capacity index scores and two measures of oil and gas industry activity (total
employment and number of business establishments within five industry categories)
yielded no statistically significant associations. By aggregating a range of
important contextual variables into a single index, the study demonstrates a
useful approach for the more systematic examination and comparison of exposure,
vulnerability and capacity for resilience among coastal communities.
PMID- 27500077
TI - Rapid advance of two mountain glaciers in response to mine-related debris
loading.
AB - Rapid glacier advance is known to occur by a range of mechanisms. However,
although large-scale debris loading has been proposed as a process for causing
rapid terminus advance, it has rarely been observed. We use satellite remote
sensing data to observe accelerated glacier terminus advance in response to
massive supraglacial loading on two glaciers in Kyrgyzstan. Over a 15 year
period, mining activity has led to the dumping of spoil of up to 180 m thick on
large parts of these valley glaciers. We find that the termini of these glaciers
advance by 1.2 and 3.2 km, respectively, at a rate of up to 350 m yr-1. Our
analysis suggests that although enhanced basal sliding could be an important
process, massive supraglacial loads have also caused enhanced internal ice
deformation that would account for most, or all, of the glacier terminus advance.
In addition, narrowing of the glacier valley and mining and dumping of ice alter
the mass balance and flow regime of the glaciers. Although the scale of
supraglacial loading is massive, this full-scale experiment provides insight into
glacier flow acceleration response where small valley glaciers are impacted by
very large volumes of landslide debris.
PMID- 27500078
TI - Peer-assisted teaching student tutors as examiners in an orthopedic surgery OSCE
station - pros and cons.
AB - BACKGROUND: The OSCE (objective structured clinical examination) is composed of
oral and practical examination in order to examine students' abilities to imply
clinical examination techniques and to interact with patients. The examiners for
this procedure can be either lecturers or peers. The aim of this work is to
evaluate the peer-assisted teaching student tutors as examiners in an orthopedic
surgery OSCE station. METHODS: We analyzed the OSCE data from 2013 to 2015.
During this period over 300 medical students were examined each year. An
evaluation was conducted at an orthopedic station and examined by peer students
to assess the advantages and disadvantages of peer-assisted teaching student
tutors as examiners. RESULTS: We have noticed that student peers are more
flexible regarding their schedule and they have been well trained for OSCE.
Concerning the economic aspects, student peers are clearly of major economic
advantage. Disadvantages were not reported in our study probably because peers
were well trained and the checklists are monitored regularly. CONCLUSION: Student
peers in OSCE are of major advantage due to their flexible time schedule and
relatively low costs. They must be well trained and the checklists are to be
monitored regularly. Our study shows that peer tutor examiners conducted the
examination as competent as lecture examiners. However, legal restrictions on the
employment of students should be considered.
PMID- 27500079
TI - Electrogenerated Chemiluminescence Reporting on Closed Bipolar Microelectrodes
and the Influence of Electrode Size.
AB - We report a fundamental study of the use of Ru(bpy)32+-based electrogenerated
chemiluminescence (ECL) as an optical reporting system for the detection of redox
active analyte on closed bipolar microelectrodes, focused on gaining an in-depth
understanding of the correlation between ECL emission intensity and
electrochemical current. We demonstrate the significant effect that the size of
the anodic and cathodic poles has on the resulting ECL signal and show how this
influences the quantitative detection of analyte on a closed bipolar electrode.
By carefully designing the geometry of the bipolar electrode, the detection
performance of the system can be tuned to different analyte concentration ranges.
We show that through a simple voltammetric study of the individual reactions, one
can understand the coupled bipolar behavior and accurately predict the ECL signal
response to a range of analyte concentrations, enabling the accurate prediction
of calibration curves.
PMID- 27500080
TI - Human Papillomavirus (HPV) Infections and the Importance of HPV Vaccination.
AB - HPV persistence is necessary for the development of anogenital cancer. Studies
show that cervical and anal HPV infections in women and in men who have sex with
men are common. Clearance of HPV infection is similarly common; few individuals
show persistence unless they are HIV-infected. HIV strongly influences the
development of cervical and anal cancer, as well as their pre-malignant
counterparts. Women with cervical and vulvar HPV-associated lesions have higher
rates of anal cancer than the general population. HPV also plays an important
role in pathogenesis of head and neck cancers, particularly oropharyngeal cancer.
Two commercially available HPV vaccines have been proven to be safe and
efficacious against cervical HPV16/18 infections and associated precancerous
lesions; one of these has also been shown to prevent HPV16/18-associated anal
lesions. The FDA has also just approved a new nonavalent HPV vaccine. HPV
vaccines will play an important role in prevention of HPV-associated cancers.
PMID- 27500081
TI - A Role for Epigenetics in Broadening the Scope of Pediatric Care in the
Prevention of Adolescent Smoking.
AB - Adolescence presents a critical opportunity to support the development of healthy
patterns of behavior and prevent future health problems. Unfortunately, there is
not yet a well-developed prevention model that allows pediatricians to initiate
and monitor prevention efforts for the substantial minority of individuals who
engage in risky behavior during adolescence. We suggest that recently developed
epigenetic technologies may provide a bridge to a new prevention paradigm in
which pediatricians screen for indicated smoking prevention services.
Specifically, since currently available tobacco use screening measures are
insensitive to low levels of use, newly developed methylation based approaches
may enhance the sensitivity of the initial screening for nascent smoking behavior
as well monitoring of outcomes. We conclude that the incorporation of Next Gen
screening technologies into standard pediatric evaluations may allow for more
effective referral to prevention programming for tobacco use. In addition to the
potential direct impact on long-term enhancement of health outcomes secondary to
smoking prevention, well-established links between smoking and other risk
behaviors suggest that expanded referral for nascent smoking may also create
opportunities to address other risky adolescent behaviors, and so decrease
several interrelated drivers of long-term health care costs.
PMID- 27500082
TI - Raoultella ornithinolytica: An unusual pathogen for prosthetic joint infection.
AB - We herein report the first case of a prosthetic joint infection caused by
Raoultella ornithinolytica in an immunocompetent patient. The clinical outcome
was favorable after a two-stage prosthetic exchange and a six-month course of
antimicrobial therapy.
PMID- 27500083
TI - Group G streptococcal myositis in a patient with myeloproliferative neoplasm.
AB - While many cases of streptococcal infection are due to Lancefield groups A and B,
there has been a rise in reported cases of infections due to group G
streptococcus. We present a case of an individual with a hematologic malignancy
who developed myositis secondary to group G streptococcus, with no clearly
identifiable source of infection. The patient was managed with antibiotic therapy
rather than surgical intervention due to high surgical risk related to severe
thrombocytopenia. Targeted antibiotics initiated early in the course of disease
may prevent the need for surgical intervention. Early diagnosis and treatment are
critical to avoid the high morbidity and mortality of life-threatening infections
caused by group G streptococcus.
PMID- 27500084
TI - Neonatal encephalitis due to Chikungunya vertical transmission: First report in
Brazil.
AB - PURPOSE: To report the first case of Chikungunya encephalitis acquired in the
perinatal period during the current outbreak in Brazil. METHODS: Case report.
RESULTS: A male neonate with 3500 g developed macular erythematous rash,
hypoactivity and fever progressing to generalized seizures. His mother had
experienced a disseminated rash and fever before delivery. EEG showed diffuse
slowing and cranial NMR was suggestive of encephalitis. Rt-PCR for Chikungunya
virus (CHIKV) was positive in cerebrospinal fluid (CSF), blood, urine and saliva.
The newborn was discharged home with neurological improvement. CONCLUSION: We
report the first case of a perinatal CHIKV infection associated with a rapidly
evolving encephalitis and an extensive dissemination of the virus as documented
by positive rt-PCR results in CSF, blood, urine and saliva in the present
outbreak in Brazil. In countries experiencing outbreaks of CHIKV infections,
clinicians and neonatologists must be familiar with the possibility of the
occurrence of neurologic complications and its possible consequences.
PMID- 27500086
TI - A Mammary-type Myofibroblastoma of the Prostate: A Case Report.
AB - We report the case of a 51-year-old gentleman presenting with obstructive and
irritative urinary symptoms, found to have a large prostate mass on imaging. A
radical prostatectomy was performed and pathological diagnosis revealed a 12 cm
mammary-type myofibroblastoma replacing the entire prostate. Mammary-type
myofibroblastoma is a rare lesion outside of the breast, and is considered
benign. This is the first reported case of a mammary-type myofibroblastoma
occurring in the prostate.
PMID- 27500085
TI - Benign or Malignant? Two Case Reports of Gigantic Prostatic Cyst.
AB - A 60-year-old male with a huge prostate cyst presented with obstruction symptom
of urethra and intestinal tract. Complete excision of the cystic prostate failed
as a result of the strong adherence and twice operations history, but we
confirmed prostate adenocarcinoma and relieved his obstruction symptom. Case 2
was a 77-year-old male with an 8 cm cyst of which biopsy showed prostate cancer
in local hospital. He was admitted 18 months later because of intestinal
obstruction. Radical resection had a satisfied result of obstruction symptom and
PSA. Here we summarized malignant characteristics of cystic lesions in prostate
or surrounding structures and management.
PMID- 27500087
TI - Endoscopic Management of Free Lying Migratory Orthopedic Screw in Bladder.
AB - 75-year old gentleman presented with acute urinary retention. He had met with
road traffic accident 15 years back and sustained pelvic fracture and bladder
rupture, underwent bladder repair and open reduction and internal fixation of
pubic symphsis. Imaging studies showed the free lying encrusted orthopedic screw
in the bladder, which was removed per urethra using nephroscope. Migratory
foreign bodies in the urinary bladder are rare. However there is a possibility of
longstanding foreign bodies in adjacent structures to erode and perforate into
the bladder. Inside the bladder these foreign bodies act as nidus for stone
formation.
PMID- 27500088
TI - Achieving better modulation of coronary atherosclerosis: its understanding,
visualization and treatment.
PMID- 27500089
TI - Therapeutic modulation of the natural history of coronary atherosclerosis:
lessons learned from serial imaging studies.
AB - Despite advances in risk prediction, preventive and therapeutic strategies,
atherosclerotic cardiovascular disease remains a major public health challenge
worldwide, carrying considerable morbidity, mortality and health economic burden.
There continues to be a need to better understand the natural history of this
disease to guide the development of more effective treatment, integral to which
is the rapidly evolving field of coronary artery imaging. Various imaging
modalities have been refined to enable detailed visualization of the pathological
substrate of atherosclerosis, providing accurate and reproducible measures of
coronary plaque burden and composition, including the presence of high-risk
characteristics. The serial application of such techniques, including coronary
computed tomography angiography (CTA), intravascular ultrasound (IVUS) and
optical coherence tomography (OCT) have uncovered important insights into the
progression of coronary plaque over time in patients with stable and unstable
coronary artery disease (CAD), and its responsiveness to therapeutic
interventions. Here we review the use of different imaging modalities for the
surveillance of coronary atherosclerosis and the lessons they have provided about
the modulation of CAD by both traditional and experimental therapies.
PMID- 27500091
TI - Prediction of cardiovascular outcomes by imaging coronary atherosclerosis.
AB - Over the last two decades, several invasive and non-invasive coronary
atherosclerosis imaging modalities have emerged as predictors of cardiovascular
outcomes in at-risk population. These modalities have demonstrated independent or
incremental prognostic information over existing/standard risk stratification
schemes, such as the Framingham risk score (FRS), by identifying characteristics
of coronary artery diseases (CADs). In this review, we begin with discussing the
importance of pre-test probability and quality of outcome measure, followed by
specific findings of each modality in relation to prognosis. We focused on both
short and long term prognostic aspects of coronary computed tomography (CT)
(including coronary calcium score and coronary angiography) and magnetic
resonance imaging as non-invasive tools, as well as invasive modalities including
intravascular ultrasound (IVUS), optical coherence tomography (OCT), near
infrared spectroscopy and Angioscopy.
PMID- 27500092
TI - Noninvasive imaging modalities to visualize atherosclerotic plaques.
AB - Atherosclerotic cardiovascular disease is becoming a major cause of death in the
world due to global epidemic of diabetes and obesity. For the prevention of
atherosclerotic cardiovascular disease, it is necessary to detect high-risk
atherosclerotic plaques prior to events. Recent technological advances enable to
visualize atherosclerotic plaques noninvasively. This ability of noninvasive
imaging helps to refine cardiovascular risk assessment in various individuals,
select optimal therapeutic strategy and evaluate the efficacy of medical
therapies. In this review, we discuss the role of the currently available imaging
modalities including computed tomography (CT), magnetic resonance imaging (MRI)
and positron emission tomography. Advantages and disadvantages of each
noninvasive imaging modality will be also summarized.
PMID- 27500090
TI - Stabilization of high-risk plaques.
AB - The prevalence of atherosclerotic cardiovascular diseases (ASCVDs) is increasing
globally and they have become the leading cause of death in most countries.
Numerous experimental and clinical studies have been conducted to identify major
risk factors and effective control strategies for ASCVDs. The development of
imaging modalities with the ability to determine the plaque composition enables
us to further identify high-risk plaque and evaluate the effectiveness of
different treatment strategies. While intensive lipid-lowering by statins can
stabilize or even regress plaque by various mechanisms, such as the reduction of
lipid accumulation in a necrotic lipid core, the reduction of inflammation, and
improvement of endothelial function, there are still considerable residual risks
that need to be understood. We reviewed important findings regarding plaque
vulnerability and some encouraging emerging approaches for plaque stabilization.
PMID- 27500093
TI - Future imaging of atherosclerosis: molecular imaging of coronary atherosclerosis
with (18)F positron emission tomography.
AB - Atherosclerosis is characterized by the formation of complex atheroma lesions
(plaques) in arteries that pose risk by their flow-limiting nature and propensity
for rupture and thrombotic occlusion. It develops in the context of disturbances
to lipid metabolism and immune response, with inflammation underpinning all
stages of plaque formation, progression and rupture. As the primary disease
process responsible for myocardial infarction, stroke and peripheral vascular
disease, atherosclerosis is a leading cause of morbidity and mortality on a
global scale. A precise understanding of its pathogenic mechanisms is therefore
critically important. Integral to this is the role of vascular wall imaging. Over
recent years, the rapidly evolving field of molecular imaging has begun to
revolutionize our ability to image beyond just the anatomical substrate of
vascular disease, and more dynamically assess its pathobiology. Nuclear imaging
by positron emission tomography (PET) can target specific molecular and
biological pathways involved in atherosclerosis, with the application of
(18)Fluoride PET imaging being widely studied for its potential to identify
plaques that are vulnerable or high risk. In this review, we discuss the
emergence of (18)Fluoride PET as a promising modality for the assessment of
coronary atherosclerosis, focusing on the strengths and limitations of the two
main radionuclide tracers that have been investigated to date: 2-deoxy-2
((18)F)fluoro-D-glucose ((18)F-FDG) and sodium (18)F-fluoride ((18)F-NaF).
PMID- 27500094
TI - Characterization of coronary atherosclerosis by intravascular imaging modalities.
AB - Coronary artery disease (CAD) is highly prevalent in Western countries and is
associated with morbidity, mortality, and a significant economic burden. Despite
the development of anti-atherosclerotic medical therapies, many patients still
continue to suffer from coronary events. This residual risk indicates the need
for better risk stratification and additional therapies to achieve more
reductions in cardiovascular risk. Recent advances in imaging modalities have
contributed to visualizing atherosclerotic plaques and defining lesion
characteristics in vivo. This innovation has been applied to refining
revascularization procedure, assessment of anti-atherosclerotic drug efficacy and
the detection of high-risk plaques. As such, intravascular imaging plays an
important role in further improvement of cardiovascular outcomes in patients with
CAD. The current article reviews available intravascular imaging modalities with
regard to its method, advantage and disadvantage.
PMID- 27500095
TI - Imaging of coronary atherosclerosis in various susceptible groups.
AB - Coronary artery disease (CAD) is the leading cause of death and disability
worldwide. Atherosclerosis, which is the primary pathophysiologic mechanism for
the development of plaque leading to CAD, is a multifactorial process resulting
from a complex interplay between genetic susceptibility and various risk factors
such as hypertension (HT), dyslipidaemia, diabetes mellitus (DM) and smoking. In
addition, influences from other disease states such as chronic kidney disease
(CKD), obesity and the metabolic syndrome as well as gender and ethnic diversity
also contribute to the disease process. Insights from pathological observations
and advances in cellular and molecular biology have helped us understand the
process of plaque formation, progression and rupture leading to events. Several
intravascular imaging techniques such as intravascular ultrasound (IVUS), Virtual
histology IVUS (VH-IVUS) and optical coherence tomography (OCT) allow in vivo
assessment of plaque burden, plaque morphology and response to therapy. In
addition, non invasive assessment using coronary artery calcium (CAC) score
allows risk stratification and plaque burden assessment whilst computed
tomography coronary angiography (CTCA) allows evaluation of luminal stenosis,
plaque characterisation and quantification. This review aims to summarise the
results of invasive and non-invasive imaging studies of coronary atherosclerosis
seen in various high-risk populations including DM, metabolic syndrome, obesity,
CKD and, gender differences and ethnicity. Understanding the phenotype of plaques
in various susceptible groups may allow potential development of personalised
therapies.
PMID- 27500096
TI - Pathology of coronary atherosclerosis and thrombosis.
AB - The process of early atherosclerotic plaque progression is characterized by the
development of pathologic intimal thickening (PIT) with lipid pool that may
transform into the necrotic core to form fibroatheroma, where infiltration of
foamy macrophages plays a crucial role. The expansion of the necrotic core is
also attributable to intraplaque hemorrhage. Thin-cap fibroatheroma (TCFA) is
characterized by a relatively large necrotic core with an overlying thin fibrous
cap measuring <65 um typically containing numerous macrophages, and is considered
to be the precursor lesion of plaque rupture which is the most common cause of
coronary thrombosis. The second common cause of acute thrombosis is plaque
erosion, while calcified nodules is known to be the least frequent cause of
coronary thrombosis. Coronary thrombosis can occur without symptoms to form
healed lesions, which contributes to an increase in plaque burden and luminal
narrowing. The process of plaque progression is generally accompanied by the
progression of calcification. An understanding of the histomorphological
characteristics of coronary plaques should provide important insights into the
pathogenesis, diagnosis, and treatment of atherosclerotic coronary disease for
both basic and clinical researchers as well as for clinicians.
PMID- 27500097
TI - Human beta-NGF gene transferred to cat corneal endothelial cells.
AB - AIM: To transfect the cat corneal endothelial cells (CECs) with recombinant human
beta-nerve growth factor gene adeno-associated virus (AAV-beta-NGF) and to
observe the effect of the expressed beta-NGF protein on the proliferation
activity of cat CECs. METHODS: The endothelium of cat cornea was torn under the
microscope and rapidly cultivated in Dulbecco's modified Eagle's medium (DMEM) to
form single layer CECs and the passage 2 endothelial cells were used in this
experiment. The recombinant human AAV-beta-NGF was constructed. The recombinant
human AAV-beta-NGF was transferred into cat CECs directly. Three groups were as
following: normal CEC control group, CEC-AAV control group and recombinant CEC
AAV-beta-NGF group. Forty-eight hours after transfection, the total RNA was
extracted from the CEC by Trizol. The expression of the beta-NGF target gene
detected by fluorescence quantitative polymerase chain reaction; proliferation
activity of the transfected CEC detected at 48h by MTT assay; the percentage of
G1 cells among CECs after transfect was detected by flow cytometry method (FCM);
cell morphology was observed under inverted phase contrast microscope. RESULTS:
The torn endothelium culture technique rapidly cultivated single layer cat
corneal endothelial cells. The self-designed primers for the target gene and
reference gene were efficient and special confirmed through electrophoresis
analysis and DNA sequencing. Forty-eight hours after transfect, the human beta
NGF gene mRNA detected by fluorescence quantitative polymerase chain reaction
showed that there was no significant difference between normal CEC control group
and CEC-AAV control group (P>0.05); there was significant difference between two
control groups and recombinant CEC-AAV-beta-NGF group (P<0.05). MTT assay showed
that transfect of recombinant AAV-beta-NGF promoted the proliferation activity of
cat CEC, while there was no significant difference between normal CEC control
group and CEC-AAV control group (P>0.05). FCM result showed that the percentage
of G1cells in CEC-AAV-NGF group was 76.8% while that in normal CEC control group
and CEC-AAV control group was 46.6% and 49.8%. CONCLUSION: Recombinant AAV-beta
NGF promotes proliferation in cat CECs by expressing bioactive beta-NGF protein
in high efficiency and suggests that its modulation can be used to treat vision
loss secondary to corneal endothelial dysfunction.
PMID- 27500098
TI - Anterior segment dysgenesis correlation with epithelial-mesenchymal transition in
Smad4 knockout mice.
AB - AIM: To explore the molecular mechanisms in lens development and the pathogenesis
of Peters anomaly in Smad4 defective mice. METHODS: Le-Cre transgenic mouse line
was employed to inactivate Smad4 in the surface ectoderm selectively.
Pathological techniques were used to reveal the morphological changes of the
anterior segment in Smad4 defective eye. Immunohistochemical staining was
employed to observe the expression of E-cadherin, N-cadherin and alpha-SMA in
anterior segment of Smad4 defective mice and control mice at embryonic (E) day
16.5. Real-time quantitative polymerase chain reaction (qPCR) was performed to
detect the expression of Snail, Zeb1, Zeb2 and Twist2 in lens of Smad4 defective
mice and control mice at E16.5. Statistical evaluations were performed using the
unpaired Student's t-test (two-tailed) by SPSS 11.0 software. RESULTS:
Conditional deletion of Smad4 on eye surface ectoderm resulted in corneal
dysplasia, iridocorneal angle closure, corneolenticular adhesions and cataract
resembling Peters anomaly. Loss of Smad4 function inhibited E-cadherin expression
in the lens epithelium cells and corneal epithelium cells in Smad4 defective eye.
Expression of N-cadherin was up-regulated in corneal epithelium and corneal
stroma. Both E-cadherin and N-cadherin were down-regulated at the future
trabecular meshwork region in mutant eye. The qPCR results showed that the
expression of Twist2 was increased significantly in the mutant lens (P<0.01).
CONCLUSION: Smad4 is essential to eye development and likely a candidate
pathogenic gene to Peters anomaly by regulating epithelial-mesenchymal
transition. Twist2 can be regulated by Smad4 and plays an essential role in lens
development.
PMID- 27500099
TI - Promotion on the differentiation of retinal Muller cells into retinal ganglion
cells by Brn-3b.
AB - AIM: To investigate the role of Brn-3b in differentiation process of stem cells
derived from retinal Muller cells into the ganglion cell. METHODS: The passage
culture method of Muller cells from retina of newborn Sprague Dawley rats was
carried out by repeated incomplete pancreatic enzyme digestion method. The cells
were detected by fluorescence-activated cell sorter (FACS), immunohistochemistry
technology and reverse transcription-polymerase chain reaction (RT-PCR) to
determine the purity. The third passage of cells was induced in the serum-free
dedifferentiation medium. The expression of the specific markers Ki-67 and nestin
of retinal stem cells was measured by RT-PCR and Western blot. The cell
proliferation of retinal stem cells was detected by 5-ethynyl-2'-deoxyuridine
(Edu) staining. The cells were randomly divided into 5 groups as follows: group
A: Brn-3bsiRNA group; group B: Brn-3b control siRNA group; group C: pGC-Brn-3b
green fluorescent protein (GFP) group; group D: pGC-GFP group; group E: control
group (without any handling). The purified Muller cells were cultured for 3-7d,
then, the percentage of ganglion cells was counted by immunofluorescence
staining. RESULTS: FACS demonstrated the purity of retinal Muller cells was more
97.44%. A few spherical cell spheres appeared. Immunofluorescence staining showed
that stem cells within the spheres were positive for retinal stem cell-specific
markers nestin (red fluorescence, 92.94%+/-6.48%) and Ki-67 (green fluorescence,
85.96%+/-6.04%). Meanwhile, RT-PCR analysis showed cell spheres in the culture to
have expressed a battery of transcripts characteristic of stem cells such as
nestin and Ki-67, which were absent in the Muller cells. Western blot analysis
further confirmed the expression of nestin and Ki-67 in the cell spheres but not
in the Muller cells. Edu staining showed most of the nuclei within the cell
spheres were stained red (82.80%+/-6.65%), suggesting the new cell spheres had
the capacity for effective proliferation. The statistics result showed the
difference between Brn-3bsiRNA group and Brn-3b control siRNA group or the
control group was significant (F=15, P<0.05), while the difference between Brn-3b
control siRNA group or the control group was not statistically significant
(P>0.05). CONCLUSION: The repeated incomplete pancreatic enzyme digestion method
is an efficient and practical method to purify retinal Muller cells. Retinal stem
cells were successfully cloned in the dedifferentiational medium. Retinal Muller
cells are accessible sources of retinal stem cells. Brn-3b is an important
regulatory gene in stem cells differentiated into retinal ganglion cell.
PMID- 27500100
TI - Promotion of axon regeneration and inhibition of astrocyte activation by alpha A
crystallin on crushed optic nerve.
AB - AIM: To explore the effects of alphaA-crystallin in astrocyte gliosis after optic
nerve crush (ONC) and the mechanism of alpha-crystallin in neuroprotection and
axon regeneration. METHODS: ONC was established on the Sprague-Dawley rat model
and alphaA-crystallin (10(-4) g/L, 4 uL) was intravitreously injected into the
rat model. Flash-visual evoked potential (F-VEP) was examined 14d after ONC, and
the glial fibrillary acidic protein (GFAP) levels in the retina and crush site
were analyzed 1, 3, 5, 7 and 14d after ONC by immunohistochemistry (IHC) and
Western blot respectively. The levels of beta Tubulin (TUJ1), growth-associated
membrane phosphoprotein-43 (GAP-43), chondroitin sulfate proteoglycans (CSPGs)
and neurocan were also determined by IHC 14d after ONC. RESULTS: GFAP level in
the retina and the optic nerve significantly increased 1d after ONC, and reached
the peak level 7d post-ONC. Injection of alphaA-crystallin significantly
decreased GFAP level in both the retina and the crush site 3d after ONC, and
induced astrocytes architecture remodeling at the crush site. Quantification of
retinal ganglion cell (RGC) axons indicated alphaA-crystallin markedly promoted
axon regeneration in ONC rats and enhanced the regenerated axons penetrated into
the glial scar. CSPGs and neurocan expression also decreased 14d after alphaA
crystallin injection. The amplitude (N1-P1) and latency (P1) of F-VEP were also
restored. CONCLUSION: Our results suggest alpha-crystallin promotes the axon
regeneration of RGCs and suppresses the activation of astrocytes.
PMID- 27500101
TI - Expression of microRNAs in fibroblast of pterygium.
AB - AIM: To screen microRNAs (miRNAs) and set up target miRNAs in pterygium. METHODS:
Primary fibroblasts were isolated from pterygium and Tenon's capsule and
cultured. Immunocytochemical analysis and Western blotting were performed to
confirm the culture of fibroblasts. In all, 1733 miRNAs were screened in the
first step by using GeneChip((r)) miRNA3.0 Array. Specific miRNAs involved in the
pathogenesis of pterygium were subsequently determined using the following
criteria: 1) high reproducibility in a repetitive test; 2) base log value of >7.0
for both control and pterygial fibroblasts; and 3) log ratio of >1.0 between
pterygial fibroblasts and control fibroblasts. RESULTS: Primary screening showed
that 887/1733 miRNAs were up-regulated and 846/1733 miRNAs were down-regulated in
pterygial fibroblasts compared with those in control fibroblasts. Of the 1733
miRNAs screened, 4 miRNAs, namely, miRNA-143a-3p, miRNA-181a-2-3p, miRNA-377-5p
and miRNA-411a-5p, met the above-mentioned criteria. Primary screening showed
that these 4 miRNAs were up-regulated in pterygial fibroblasts compared with
control fibroblasts and that miRNA-143a-3p had the highest mean ratio compared
with the miRNAs in control fibroblasts. CONCLUSION: miRNA-143a-3p, miRNA-181a-2
3p, miRNA-377-5p and miRNA-411a-5p are up-regulated in pterygial fibroblasts
compared with control fibroblasts, suggesting their involvement in the
pathogenesis of pterygium.
PMID- 27500102
TI - Retraction Notice.
AB - [This retracts the article DOI: 10.18240/ijo.2016.03.07.].
PMID- 27500103
TI - Comparison of corneal biomechanical properties in normal tension glaucoma
patients with different visual field progression speed.
AB - AIM: To compare the corneal biomechanical properties difference by ocular
response analyzer (ORA) in normal tension glaucoma (NTG) patients with different
visual field (VF) progression speed. METHODS: NTG patients with well-controlled
Goldmann applanation tonometer (GAT) who routinely consulted Kitasato University
Hospital Glaucoma Department between January 2010 and February 2014 were
enrolled. GAT and ORA parameters including corneal compensated intraocular
pressure (IOPcc), Goldmann estimated intraocular pressure (IOPg), corneal
hysteresis (CH), corneal resistance factor (CRF) were recorded. VF was tested by
Swedish interactive threshold algorithm (SITA)-standard 30-2 fields. All patients
underwent VF measurement regularly and GAT did not exceed 15 mm Hg at any time
during the 3y follow up. Patients were divided into four groups according to VF
change over 3y, and ORA findings were compared between the upper 25(th)
percentile group (slow progression group) and the lower 25(th) percentile group
(rapid progression group). RESULTS: Eighty-two eyes of 56 patients were studied.
There were 21 eyes (21 patients) each in rapid and slow progression groups
respectively. GAT, IOPcc, IOPg, CH, CRF were 12.1+/-1.4 mm Hg, 15.8+/-1.8 mm Hg,
12.8+/-2.0 mm Hg, 8.4+/-1.1 mm Hg, 7.9+/-1.3 mm Hg respectively in rapid
progression group and 11.5+/-1.3 mm Hg, 13.5+/-2.1 mm Hg, 11.2+/-1.6 mm Hg, 9.3+/
1.1 mm Hg, 8.2+/-0.9 mm Hg respectively in slow progression group (P=0.214,
<0.001, 0.007, 0.017, 0.413, respectively). In bivariate correlation analysis,
IOPcc, IOPcc-GAT and CH were significant correlated with mDeltaMD (r=-0.292,
0.312, 0.228 respectively, P=0.008, 0.004, 0.039 respectively). CONCLUSION:
Relatively rapid VF progression occurred in NTG patients whose IOPcc are rather
high, CH are rather low and the difference between IOPcc and GAT are relatively
large. Higher IOPcc and lower CH are associated with VF progression in NTG
patients. This study suggests that GAT measures might underestimate the IOP in
such patients.
PMID- 27500104
TI - Diurnal changes in retinal nerve fiber layer thickness with obstructive sleep
apnea/hypopnea syndrome.
AB - AIM: To compare the retinal nerve fiber layer (RNFL) thickness in the morning and
evening in Thai patients with varying degrees of obstructive sleep apnea/hypopnea
syndrome (OSAHS). METHODS: In this cross-sectional study, potential OSAHS
patients at Siriraj Hospital underwent polysomnography to determine the severity
of OSAHS and an eye examination (including best corrected visual acuity, slit
lamp examination, and Goldmann applanation tonometry). RNFL thickness was
recorded once in the morning and once in the evening, using spectral domain
optical coherence tomography. Thickness was expressed as an average and given for
each quadrant. Patients with ocular or systemic diseases that might affect RNFL
thickness were excluded. RESULTS: Forty-one eyes of 41 patients were classified
into 4 OSAHS groups. The average and mean RNFL thickness in most of the four
quadrants of the severe OSAHS group trended toward being less than those in the
comparable quadrants of the other groups in both the morning and evening. In the
moderate OSAHS group, the average RNFL thickness and temporal and superior
quadrant thickness in the morning were significantly higher than in the evening
(P=0.01, P=0.01, and P=0.03, respectively). In the severe OSAHS group, the
inferior quadrant thickness in the morning was significantly higher than in the
evening (P=0.03). CONCLUSION: The RNFL thickness in the morning was higher than
in the evening in moderate OSAHS.
PMID- 27500105
TI - Epidemiology and risk factors of retinoblastoma in Chongqing area.
AB - AIM: To investigate the risk factors of retinoblastoma in Chongqing and offer the
bases for scientific measures. METHODS: One hundred and thirty-three
retinoblastoma patients were taken as case group, and 133 children were taken as
control group in 1:1 ratio. The relevant factors were collected from a
questionnaire survey which was made by our research group. First, Chi-square and
t-test were used to discuss the various factors, and then the logistic regression
analysis was made by statistics software SPSS17.0 based on the result of 266
people. RESULTS: Single factor analysis results showed the differences between
the two groups were statistically significant (P<0.05) in 17 factors which were
education level of their parents, occupation of their parents, exposure to
harmful chemicals of their parents 6mo before pregnancy, the history of pelvic
inflammatory disease of mother before pregnancy, childbearing history of their
parents, pregnant age of their parents, the medication history of father 6 mo
before pregnancy, living place of their parents, the pollution living place of
mother, hobbies of their parents. Multivariate analysis showed that the living
place of parents, mother who feed pets before pregnancy, and exposure to harmful
chemicals of father before pregnancy were the independent risk factors of
retinoblastoma (P<0.05). CONCLUSION: The living place of parents, mother who feed
pets before pregnancy, exposure to harmful chemicals of father before pregnancy
were the risk factors of retinoblastoma which affects the occurrence of
retinoblastoma in a certain extent.
PMID- 27500106
TI - Risk factors of rhegmatogenous retinal detachment associated with choroidal
detachment in Chinese patients.
AB - AIM: To comprehensively analyze the risk factors of rhegmatogenous retinal
detachment (RRD) associated with choroidal detachment (CD). METHODS: A total of
265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All
patients had systemic and ophthalmologic examination. CD was diagnosed by
indirect ophthalmoscopy, B-scan ultrasonography, and ultrasound biomicroscope
(UBM). Each parameter was compared between patients of RRD and rhegmatogenous
retinal detachment associated with choroidal detachment (RRDCD). Logistic
regression analysis was used to determine the independent risk factors of CD.
RESULTS: There were 52 eyes (19.62%) with CD. Pseudophakia was more commonly seen
in RRDCD (21.15% vs 6.10%, P=0.002). Intraocular pressure (IOP) was lower (8.60+/
3.62 vs 12.96+/-3.55, P<0.001), best-corrected visual acuity was worse [3.00
(2.00 to 3.00) vs 1.92 (1.22 to 3.00), P=0.001], and refractive error was more
myopic [-4 (-9 to -2) vs -2 (-6 to 0), P=0.007] in RRDCD. Eyes with RRDCD had
larger extent of retinal detachment (P=0.007). In RRDCD, 34.62% of eyes presented
with multiple holes (P=0.044) and 25.00% with macular holes (P=0.012), compared
with 20.66% and 14.08% in RRD. High myopia (P=0.039), low IOP (P=0.017), and
larger extent of retinal detachment (P<0.001) were significant and independent
risk factors for developing CD. CONCLUSION: For CD in RRD, related factors
include BCVA, IOP, lens status, refractive error, extent of retinal detachment,
number of holes, and macular hole. Larger extent of retinal detachment, high
myopia, and low IOP are significant and independent risk factors.
PMID- 27500107
TI - Predictive factors for postoperative visual function of primary chronic
rhegmatogenous retinal detachment after scleral buckling.
AB - AIM: To evaluate predictive factors for postoperative visual function of primary
chronic rhegmatgenous retinal detachment (RRD) after sclera buckling (SB).
METHODS: Totally 48 patients (51 eyes) with primary chronic RRD were included in
this prospective interventional clinical cases study, which underwent SB alone
from June 2008 to December 2014. Age, sex, symptoms duration, detached extension,
retinal hole position, size, type, fovea on/off, proliferative vitreoretinopathy
(PVR), posterior vitreous detachment (PVD), baseline best corrected visual acuity
(BCVA), operative duration, follow up duration, final BCVA were measured. Pearson
correlation analysis, Spearman correlation analysis and multivariate linear
stepwise regression were used to confirm predictive factors for better final
visual acuity. Student's t-test, Wilcoxon two-sample test, Chi-square test and
logistic stepwise regression were used to confirm predictive factors for better
vision improvement. RESULTS: Baseline BCVA was 0.8313+/-0.6911 logMAR and final
BCVA was 0.4761+/-0.4956 logMAR. Primary surgical success rate was 92.16%
(47/51). Correlation analyses revealed shorter symptoms duration (r=0.3850,
P=0.0053), less detached area (r=0.5489, P<0.0001), fovea (r=0.4605, P=0.0007),
no PVR (r=0.3138, P=0.0250), better baseline BCVA (r=0.7291, P<0.0001), shorter
operative duration (r=0.3233, P=0.0207) and longer follow up (r=-0.3358,
P=0.0160) were related with better final BCVA, while independent predictive
factors were better baseline BCVA [partial R-square (PR(2))=0.5316, P<0.0001],
shorter symptoms duration (PR(2)=0.0609, P=0.0101), longer follow up duration
(PR(2)=0.0278, P=0.0477) and shorter operative duration (PR(2)=0.0338, P=0.0350).
Patients with vision improvement took up 49.02% (25/51). Univariate and
multivariate analyses both revealed predictive factors for better vision
improvement were better baseline vision [odds ratio (OR) =50.369, P=0.0041] and
longer follow up duration (OR=1.144, P=0.0067). CONCLUSION: Independent
predictive factors for better visual outcome of primary chronic RRD after SB are
better baseline BCVA, shorter symptoms duration, shorter operative duration and
longer follow up duration, while independent predictive factors for better vision
improvement after operation are better baseline vision and longer follow up
duration.
PMID- 27500108
TI - Effects of two different doses of intravitreal bevacizumab on subfoveal choroidal
thickness and retinal vessel diameter in branch retinal vein occlusion.
AB - AIM: To investigate the effects of two different doses of intravitreal
bevacizumab on subfoveal choroidal thickness (SFChT) and retinal vessel diameter
in patients with branch retinal vein occlusion. METHODS: An interventional,
restrospective study of 41 eyes of 41 patients who had completed 12mo of follow
up, divided into group 1 (1.25 mg of bevacizumab, 21 eyes of 21 patients) and
group 2 (2.5 mg of bevacizumab, 20 eyes of 21 patients). Complete ophthalmic
examination, fluorescein angiography, enhanced depth imaging optical coherence
tomography and measurement of retinal vessel diameter with IVAN software were
performed at baseline and follow-up. RESULTS: The SFChT changed from 279.1 (165
431) um at baseline to 277.0 (149-413) um at 12mo in group 1 (P=0.086), and from
301.4 (212-483) um to 300.3 (199-514) um in group 2 (P=0.076). The central
retinal arteriolar equivalent (CRAE) changed from 128.8+/-11.2 um at baseline to
134.5+/-8.4 um at 12mo in group 1, and from 134.6+/-9.0 um to 131.4+/-12.7 um in
group 2 (P=0.767). The central retinal venular equivalent (CRVE) changed from
204.1+/-24.4 um at baseline to 196.3+/-28.2 um at 12mo in group 1, and from
205.8+/-16.3 um to 194.8+/-18.2 um in group 2 (P=0.019). The mean central macular
thickness (P<0.05) and average best-corrected visual acuity (BCVA; P<0.05)
improved in both groups. CONCLUSION: Changes in the SFChT are not statistically
significant and not different according to the doses of bevacizumab. The CRAE did
not show significant change, however, the CRVE showed significant decrease
regardless of the dose.
PMID- 27500109
TI - Comparison of corneal flaps created by Wavelight FS200 and Intralase FS60
femtosecond lasers.
AB - AIM: To assess and compare the morphology of corneal flaps created by the
Wavelight FS200 and Intralase FS60 femtosecond lasers in laser in situ
keratomileusis (LASIK). METHODS: Four hundred eyes of 200 patients were enrolled
in this study and divided into Wavelight FS200 groups (200 eyes) and Intralase
FS60 groups (200 eyes). Fourier-domain optical coherence tomography (RTVue OCT)
was used to measure the corneal flap thickness of 36 specified measurements on
each flap one week after surgery. Results were used to analyze the regularity,
uniformity and accuracy of the two types of LASIK flaps. RESULTS: The mean
thickness of corneal flap and central flap was 105.71+/-4.72 um and 105.39+/-4.50
um in Wavelight FS200 group and 109.78+/-11.42 um and 109.15 +/-11.59 um in
Intralase FS60 group, respectively. The flaps made with the Wavelight FS200
femtosecond laser were thinner than those created by the Intralase FS60
femtosecond laser (P=0.000). Corneal flaps in the 2 groups were uniform and
regular, showing an almost planar configuration. But the Wavelight FS200 group
has more predictability and uniformity of flap creation. The mean deviation
between achieved and attempted flap thickness was smaller in the Wavelight FS200
group than that in the Intralase FS60 group, which were 5.18+/-3.71 um and 8.68+/
7.42 um respectively. The deviation of more than 20 um was 0.2% measurements in
Wavelight FS200 group and 8.29% measurements in Intralase FS60 group. CONCLUSION:
The morphologies of flaps created by Wavelight FS200 are more uniform and thinner
than those created by Intralase FS60.
PMID- 27500110
TI - Post-operative strabismus control and motor alignment for basic intermittent
exotropia.
AB - AIM: To assess strabismus control and motor ocular alignment for basic exotropia
surgery at 5y follow-up. METHODS: The medical records of 80 consecutive patients
aged less than 17 years of age, who underwent surgery for basic exotropia by a
single surgeon between years 2000 to 2009 and completed a minimum of 5y follow-up
post-operatively were reviewed. Pre- and post-operative characteristics were
documented at 1wk, 6mo, 1, 3 and 5y follow-up. Subjects at 5-year follow-up were
assigned to the success group if they had a post-operative angle of deviation
within 10 prism diopters of exotropia or within 5 prism diopters of esotropia for
distance on prism cover test, and had moderate to good strabismus control. The
remaining subjects were assigned to the failure group. RESULTS: Post-operative
surgical success at one week was 75%, which decreased to 41% at 5y follow-up. The
success group was noted to have more patching pre-operatively (P=0.003). The
duration of patching a day (P=0.020) and total duration of patching pre
operatively (P=0.030) was higher in the success group. Surgical success at 1y
(P=0.004) and 3y (P=0.002) were associated with higher surgical success at 5y
follow-up. CONCLUSION: Post-operative motor alignment and strabismus control for
basic exotropia surgery at 1y and beyond is associated with higher exotropia
surgery success at 5-year follow-up. There is an association between pre
operative patching and 5-year surgical success of basic intermittent exotropia
surgery.
PMID- 27500111
TI - Comparison of therapeutic effects of topical azithromycin solution and systemic
doxycycline on posterior blepharitis.
AB - AIM: To compare the effect of azithromycin drop and doxycycline capsule on
treatment of posterior blepharitis. METHODS: Fifty patients (100 eyes) with
moderate posterior blepharitis, randomly divided into two therapeutic groups; all
the patients got warm eyelid compress and massage three times a day for 3wk. In
addition the first group got azithromycin 1% drop, twice daily for 1wk and then
one drop daily for 2wk. The second group got oral doxycycline 100 mg daily for
3wk. At the end of the research, patients' signs and symptoms were compared
together. ANOVA, Chi-square and Mann-Whitney tests were used for statistical
analysis. RESULTS: Topical therapy with azithromycin and oral therapy with
doxycycline relieved signs and symptoms after 3wk. There were no significant
differences between symptoms healing rate and foreign body sensation healing in
these two groups (P>0.05). However, azithromycin drop was more effective in
reduction of eye redness and doxycycline was more effective in meibomian glands
plugging healing and reducing the corneal staining. CONCLUSION: Topical
azithromycin could have similar effects as oral doxycycline on posterior
blepharitis in improving subjective symptoms. However, doxycycline can reduce
objective signs such as ocular surface staining and meibomian gland plugging more
than azithromycin.
PMID- 27500113
TI - Comparison of the efficacy of anti-VEGF monotherapy versus PDT and intravitreal
anti-VEGF combination treatment in AMD: a Meta-analysis and systematic review.
AB - AIM: To compare the effect of anti-vascular endothelial growth factor (VEGF)
monotherapy versus photodynamic therapy (PDT) and anti-VEGF combination treatment
in age-related macular degeneration (AMD). METHODS: A computerized online search
was performed using PubMed, Web of Science and the Cochrane Library. Studies that
compared anti-VEGF monotherapy with PDT and anti-VEGF combination treatment of
AMD and were designed as randomized controlled trials were included. The means
and standard deviations of the best-corrected visual acuity (BCVA), central
retinal thickness (CRT), number of treatments and proportions of patients who
gained BCVA >=15, 10, 5, or 0 letters at 12(th) month were extracted. A
systematic review and Meta-analysis of the comparison of the two approaches was
conducted using Review Manager 5.2. Subgroup. A sensitivity analysis was also
performed. RESULTS: Eight studies were included. When the subgroup and
sensitivity analysis was conducted, the results indicated that in the findings
that included the monotherapy group and PDT (standard fluence, SF) group of
Kaiser's study, the patients in the monotherapy group had a better BCVA compared
with the combination group at 12(th) month in the PDT (SF) subgroup [weighted
mean difference (WMD): 3.54; 95%CI: 0.36 to 6.73; P=0.03], and there were more
patients who gained >=15 letters of BCVA in the monotherapy group compared with
the combination group in the total result [odds ratio (OR): 1.41; 95%CI: 1.02 to
1.95; P=0.04]. The same conclusion was obtained in the total result that included
the monotherapy group and PDT (reduced fluence, RF) group of Kaiser's study (OR:
1.56; 95%CI: 1.13 to 2.15; P=0.007). However, there were no significant
differences in the other indexes between the two therapies. CONCLUSION: We found
that anti-VEGF monotherapy is more effective on the recovery of visual acuity
than combination therapy and more researches with lager sample size should be
performed to study on the effect of the two therapy approaches on CRT and number
of injections.
PMID- 27500112
TI - Sub-threshold micro-pulse diode laser treatment in diabetic macular edema: A Meta
analysis of randomized controlled trials.
AB - AIM: To examine possible differences in clinical outcomes between sub-threshold
micro-pulse diode laser photocoagulation (SDM) and traditional modified Early
Treatment Diabetic Retinopathy Study (mETDRS) treatment protocol in diabetic
macular edema (DME). METHODS: A comprehensive literature search using the
Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for
DME. The participants were type I or type II diabetes mellitus with clinically
significant macular edema treated by SDM from previously reported randomized
controlled trials (RCTs). The primary outcome measures were the changes in the
best corrected visual acuity (BCVA) and the central macular thickness (CMT) as
measured by optical coherence tomography (OCT). The secondary outcomes were the
contrast sensitivity and the damages of the retina. RESULTS: Seven studies were
identified and analyzed for comparing SDM (215 eyes) with mETDRS (210 eyes) for
DME. There were no statistical differences in the BCVA after treatment between
the SDM and mETDRS based on the follow-up: 3mo (MD, -0.02; 95% CI, -0.12 to 0.09;
P=0.77), 6mo (MD, -0.02; 95% CI, -0.12 to 0.09; P=0.75), 12mo (MD, -0.05; 95% CI,
-0.17 to 0.07; P=0.40). Likewise, there were no statistical differences in the
CMT after treatment between the SDM and mETDRS in 3mo (MD, -9.92; 95% CI, -28.69
to 8.85; P=0.30), 6mo (MD, -11.37; 95% CI, -29.65 to 6.91; P=0.22), 12mo (MD,
8.44; 95% CI, -29.89 to 46.77; P=0.67). Three RCTs suggested that SDM laser
results in good preservation of contrast sensitivity as mETDRS, in two different
follow-up evaluations: 3mo (MD, 0.05; 95% CI, 0 to 0.09; P=0.04) and 6mo (MD,
0.02; 95% CI, -0.10 to 0.14; P=0.78). Two RCTs showed that the SDM laser
treatment did less retinal damage than that mETDRS did (OR, 0.05; 95% CI, 0.02 to
0.13; P<0.01). CONCLUSION: SDM laser photocoagulation shows an equally good
effect on visual acuity, contrast sensitivity, and reduction of DME as compared
to conventional mETDRS protocol with less retinal damage.
PMID- 27500114
TI - Metabolic syndrome risk factors and dry eye syndrome: a Meta-analysis.
AB - AIM: To explore the relationship between metabolic risk factors and dry eye
syndrome (DES). METHODS: Retrieved studies on the association of metabolic
syndrome risk factors (hypertension, hyperglycemia, obesity, and hyperlipidemia)
and DES were collected from PubMed, Web of Science, and the Cochrane Library in
December 2015. Odds ratio (OR) with 95% confidence interval (CI) were pooled to
evaluate the final relationship. Subgroup analyses were conducted according to
diagnostic criteria of DES. RESULTS: Nine cross-sectional studies and three case
control studies were included in this Meta-analysis. The pooled results showed
that people with hypertension, hyperglycemia, and hyperlipidemia had a higher
risk of suffering from DES (P<0.05), especially the typical DES symptoms. On the
other hand, obesity did not increase the risk of DES. CONCLUSION: The present
Meta-analysis suggests that all metabolic risk factors except obesity were risk
factors for DES.
PMID- 27500115
TI - Profitability analysis of a femtosecond laser system for cataract surgery using a
fuzzy logic approach.
AB - AIM: To define the financial and management conditions required to introduce a
femtosecond laser system for cataract surgery in a clinic using a fuzzy logic
approach. METHODS: In the simulation performed in the current study, the costs
associated to the acquisition and use of a commercially available femtosecond
laser platform for cataract surgery (VICTUS, TECHNOLAS Perfect Vision GmbH,
Bausch & Lomb, Munich, Germany) during a period of 5y were considered. A
sensitivity analysis was performed considering such costs and the countable
amortization of the system during this 5y period. Furthermore, a fuzzy logic
analysis was used to obtain an estimation of the money income associated to each
femtosecond laser-assisted cataract surgery (G). RESULTS: According to the
sensitivity analysis, the femtosecond laser system under evaluation can be
profitable if 1400 cataract surgeries are performed per year and if each surgery
can be invoiced more than $500. In contrast, the fuzzy logic analysis confirmed
that the patient had to pay more per surgery, between $661.8 and $667.4 per
surgery, without considering the cost of the intraocular lens (IOL). CONCLUSION:
A profitability of femtosecond laser systems for cataract surgery can be obtained
after a detailed financial analysis, especially in those centers with large
volumes of patients. The cost of the surgery for patients should be adapted to
the real flow of patients with the ability of paying a reasonable range of cost.
PMID- 27500116
TI - Prevalences and causes of vision impairment in elderly Chinese: a socioeconomic
perspective of a comparative report nested in Jiangsu Eye Study.
AB - AIM: To survey the prevalence and causes of visual impairment/blindness among
elderly Chinese from different socioeconomic status in community-based design.
METHODS: Cluster-sampling randomly selected residents from Binhu and Funing
District, two areas representing different socioeconomic levels in China with
Binhu in an advanced status and Funing in less-developed area. The participants
subjected to ophthalmic examination. The presenting visual acuity (PVA) and best
corrected visual acuity (BCVA) were recorded. Visual impairment and blindness
were defined according to World Health Organization criteria. The causes of
visual impairment/blindness were identified by ophthalmic examination and/or
questionnaire. The socioeconomic status included the per capita gross domestic
product, numbers of hospital with ophthalmic service and the number of
ophthalmologists per 1 million residents. RESULTS: We successfully included 12
867 participants form 2 areas in this study. The prevalence of PVA impairment
(<20/63 to >=20/400) in the better eye was 5.4% in Binhu and 23.6% in Funing,
while the prevalence of blindness (<20/400) was 0.9% in Binhu and 2.3% in Funing.
With BCVA, the prevalence of visual impairment was 2.4% in Binhu and 6.4% in
Funing, while the prevalence of blindness was 0.8% in Binhu and 1.6% in Funing.
The participants with older age and female gender had higher prevalence in visual
impairment and blindness. The highest prevalences of vision impairment and
blindness evaluated by BCVA at >80y age group reached 20.4% and 6.3%
respectively. The prevalences of vision impairment and blindness evaluated by
BCVA were 3.5% and 1.0% in male and 5.0% and 1.3% in female. The above
differences were statistically significant (P<0.05). The predominant causes of
visual impairment and blindness were cataract, retinal disorders and uncorrected
refractive error in both areas. The socioeconomic status was associated with
visual impairment and blindness. CONCLUSION: This community-based study build a
sufficient sample size for an ophthalmic survey. Our data show the disparities on
socioeconomic development and genders in visual impairment and blindness in
China. Special emphasis of ophthalmic service should be placed on females and
less-developed area.
PMID- 27500117
TI - Device interchangeability on anterior chamber depth and white-to-white
measurements: a thorough literature review.
AB - We have reviewed a set of recently published studies that compared the anterior
chamber depth (ACD) and/or white-to-white (WTW) distance obtained by means of
different measuring devices. Since some of those studies reached contradictory
conclusions regarding device interchangeability, this review was carried out in
attempting to clarify which clinical devices can or cannot be considered as
interchangeable in clinical practice to measure ACD and/or WTW distance, among
these devices: A-scan, ultrasound biomicroscopy, Orbscan and Orbscan II
(Bausch&Lomb Surgical Inc., San Dimas, California, USA), Pentacam and Pentacam HR
(Oculus, Wetzlar, Germany), Galilei (Ziemer, Switzerland), Visante optical
coherence tomography (Visante OCT, Carl Zeiss Meditec Inc., Dublin, California,
USA), IOLMaster (Carl Zeiss Meditec, Jena, Germany), and Lenstar LS 900/Biograph
(Haag-Streit AG, Koeniz, Switzerland/Alcon Laboratories Inc., Ft Worth, Texas,
USA).
PMID- 27500119
TI - Comment on roles of tissue plasminogen activator and its inhibitor in
proliferative diabetic retinopathy.
PMID- 27500120
TI - Intensified intravitreal bevacizumab treatment regime for type 1 and 2 idiopathic
macular telangiectasia.
PMID- 27500121
TI - A surprising visual improvement following a prolonged 5-month retained subfoveal
perfluorocarbon liquid.
PMID- 27500118
TI - The effect of lens aging and cataract surgery on circadian rhythm.
AB - Many organisms have evolved an approximately 24-hour circadian rhythm that allows
them to achieve internal physiological homeostasis with external environment.
Suprachiasmatic nucleus (SCN) is the central pacemaker of circadian rhythm, and
its activity is entrained to the external light-dark cycle. The SCN controls
circadian rhythm through regulating the synthesis of melatonin by pineal gland
via a multisynaptic pathway. Light, especially short-wavelength blue light, is
the most potent environmental time cue in circadian photoentrainment. Recently,
the discovery of a novel type of retinal photoreceptors, intrinsically
photosensitive retinal ganglion cells, sheds light on the mechanism of circadian
photoentrainment and raises concerns about the effect of ocular diseases on
circadian system. With age, light transmittance is significantly decreased due to
the aging of crystalline lens, thus possibly resulting in progressive loss of
circadian photoreception. In the current review, we summarize the circadian
physiology, highlight the important role of light in circadian rhythm regulation,
discuss about the correlation between age-related cataract and sleep disorders,
and compare the effect of blue light- filtering intraocular lenses (IOLs) and
ultraviolet only filtering IOLs on circadian rhythm.
PMID- 27500122
TI - High sensitivity of diffusion tensor imaging in discriminating idiopathic
demyelinating optic neuritis.
PMID- 27500123
TI - Apocrine adenocarcinoma of the eyelid.
PMID- 27500124
TI - All Hands on Deck: Nurses and Cancer Care Delivery in Women's Health.
PMID- 27500125
TI - DNA Repair and Cytokines: TGF-beta, IL-6, and Thrombopoietin as Different
Biomarkers of Radioresistance.
AB - Double strand breaks (DSBs) induced by radiotherapy are highly cytotoxic lesions,
leading to chromosomal aberrations and cell death. Ataxia-telangiectasia-mutated
(ATM)-dependent DNA-damage response, non-homologous end joining, and homologous
recombination pathways coordinately contribute to repairing DSBs in higher
eukaryotes. It is known that the expression of DSB repair genes is increased in
tumors, which is one of the main reasons for radioresistance. The inhibition of
DSB repair pathways may be useful to increase tumor cell radiosensitivity and may
target stem cell-like cancer cells, known to be the most radioresistant tumor
components. Commonly overexpressed in neoplastic cells, cytokines confer
radioresistance by promoting proliferation, survival, invasion, and angiogenesis.
Unfortunately, tumor irradiation increases the expression of various cytokines
displaying these effects, including transforming growth factor-beta and
interleukin-6. Recently, the capabilities of these cytokines to support DNA
repair pathways and the ATM-dependent DNA response have been demonstrated.
Thrombopoietin, essential for megakaryopoiesis and very important for
hematopoietic stem cell (HSC) homeostasis, has also been found to promote DNA
repair in a highly selective manner. These findings reveal a novel mechanism
underlying cytokine-related radioresistance, which may be clinically relevant.
Therapies targeting specific cytokines may be used to improve radiosensitivity.
Specific inhibitors may be chosen in consideration of different tumor
microenvironments. Thrombopoietin may be useful in fending off irradiation
induced loss of HSCs.
PMID- 27500126
TI - Perspective of Postpartum Depression Theories: A Narrative Literature Review.
AB - Postpartum depression is the most prevalent emotional problem during a women's
lifespan. Untreated postpartum depression may lead to several consequences such
as child, infant, fetal, and maternal effects. The main purpose of this article
is to briefly describe different theoretical perspectives of postpartum
depression. A literature search was conducted in Psych Info, PubMed, and Science
Direct between 1950 and 2015. Additional articles and book chapters were
referenced from these sources. Different theories were suggested for developing
postpartum depression. Three theories, namely, biological, psychosocial, and
evolutionary were discussed. One theory or combinations of psychosocial,
biological, and evolutionary theories were considered for postpartum depression.
The most important factor that makes clinicians' choice of intervention is their
theoretical perspectives. Healthcare providers and physicians should help women
to make informed choices regarding their treatment based on related theories.
PMID- 27500127
TI - Comparative Study of Efficacy and Safety of Topical Squaric Acid Dibutylester and
Diphenylcyclopropenone for the Treatment of Alopecia Areata.
AB - BACKGROUND: Topical squaric acid dibutylester and diphenylcyclopropenone are
still the most effective therapy for alopecia areata among widely available
treatment options. Hence, it is important to know which one is more effective and
safer between the two. AIMS: The aim of this study was to compare topical squaric
acid dibutylester and diphenylcyclopropenone for the treatment of alopecia areata
in terms of their efficacy and side effects. SUBJECTS AND METHODS: In the time
period of January-March 2015, a total of 40 patients were selected for this study
from the outpatient department of Rajendra Institute of Medical Sciences, Ranchi.
After dropout of 16 patients, the remaining 24 patients were randomly divided
into two groups; that is, group A for squaric acid dibutylester and group B for
diphenylcyclopropenone. Each group received treatment for 6 months between March
November 2015. Their efficacy and side effects were compared. STATISTICAL TEST:
Unpaired student t-test was performed. P < 0.05 was considered to be significant
and 95% confidence interval was also used to evaluate the efficacy. RESULTS: The
mean values of percentage change in baseline severity of alopecia tool score for
squaric acid dibutylester and diphenylcyclopropenone were 52.25 and 34.45,
respectively. At 6 months, 95% confidence interval was 43.5-61% for group A and
25-44% for group B. In 58.33% of group A patients, A3 (50-74%) grade of
improvement was observed, whereas in group B patients, it was 33.33%. A4 grade of
improvement (75-99%) was also seen in 1 patient of group A. Minor side effects
were seen in 2 patients of group A and 10 patients of group B. None of the group
A patients showed major side effects, however, 2 patients suffered major side
effects in group B. CONCLUSIONS: Between squaric acid dibutylester and
diphenylcyclopropenone, squaric acid dibutylester is more efficacious. Further,
frequencies of major and minor side effects are also lower than
diphenylcyclopropenone.
PMID- 27500128
TI - Cardiovascular Responses to an Isometric Handgrip Exercise in Females with
Prehypertension.
AB - BACKGROUND: Hypertensive individuals are known to exhibit greater increases in
blood pressure during an isometric handgrip exercise (IHE) than their
normotensive counterparts. AIM: This study tests the hypothesis that, compared to
normotensive individuals, prehypertensive individuals exhibit an exaggerated
response to IHE. MATERIALS AND METHODS: In this study, the effects of IHE were
compared in matched prehypertensive vs. normotensive healthy African-American
females. Six healthy young adult African-American female university students were
screened in a physician's office for blood pressure in the range of
prehypertension, systolic blood pressure (SBP) 120-139 mmHg and diastolic blood
pressure (DBP) 80-89 mmHg. Six young adult African-American women were also
recruited to serve as a healthy normotensive control group with SBP <=119 mmHg
and DBP <=79 mmHg. Cardiovascular fitness was determined by peak oxygen uptake
(VO2 peak) measured during a progressive exercise test. RESULTS: During the
handgrip exercise, the prehypertensive group exhibited greater increases in SBP
(from 139 +/- 6 to 205 +/- 11 mmHg, +48%) than the controls (from 132 +/- 3 to
145 +/- 3 mmHg, +10%); intergroup difference P < 0.001. The prehypertensive group
also exhibited greater increases in DBP (from 77 +/- 2 to 112 +/- 5 mmHg, +46%)
compared to the controls (from 72 +/- 3 to 78 +/- 4 mmHg, +8%); intergroup
difference P < 0.001. The increase in systemic vascular resistance was also
greater in the prehypertensive group (from 1713 +/- 91 to 2807 +/- 370 dyne.s.cm(
5), +64%) than in the controls (from 1668 +/- 80 to 1812 +/- 169 dyne.s.cm(-5),
+9%); intergroup difference P < 0.05. CONCLUSION: These results suggest that
blood pressure measurements performed during IHE may be a useful screening tool
in evaluating prehypertensive individuals for antihypertensive treatments.
PMID- 27500129
TI - Effect of Statins on the Mortality of Bacteremic Patients: A Systematic Review
and Meta-analysis of Clinical Trials.
AB - BACKGROUND: Statins modify inflammatory cell signaling during the immune response
to infection. This has been considered as a pleotropic effect. Effects of statins
in inflammatory conditions such as bacteremia have been found to be
controversial. AIMS: We examined the effect of statins on the mortality of
bacteremia patients. MATERIALS AND METHODS: Major databases were searched for the
pertinent clinical trials. RESULTS: Six cohort studies comprising 7553 patients
were included. Hospital mortality was lower (15.36% vs 22.28%) in patients on
statin. CONCLUSIONS: There may be a potential role of statins in similar
inflammatory and infective conditions.
PMID- 27500130
TI - Acute Bowel Obstruction in a Giant Recurrent Right Bochdalek's Hernia: A Report
of Complication on Both Sides of the Diaphragm.
AB - CONTEXT: Diagnosis of congenital Bochdalek's hernia (BH) in adulthood is
extremely rare and requires a fastidious surgical repair, the failure of which
might result in a recurrence with severe complications. We report a rare case of
a giant, right BH that recurred after surgical repair and was complicated with
complete bowel obstruction. CASE REPORT: A 51-year-old Saudi male, with past
surgical history of laparotomy that failed to repair BH, presented to the
emergency room with severe abdominal pain, vomiting, and hypovolemic shock.
Computerized tomography (CT) showed an unusual picture of closed-loop bowel
obstruction above and below the diaphragm. We carried out laparotomy and
thoracotomy that achieved lysis of adhesions, reduction of bowel, and repair of
diaphragmatic defect. CONCLUSION: Acute presentation of complicated BH poses a
formidable challenge because of its rarity and complexity. The preferred approach
for elective repair of adult BH is debatable, where surgeons-guided by hernia
type and biased by their experience-recommend either laparotomy or thoracotomy.
Nevertheless, a complicated, giant, recurrent BH typically requires both
laparotomy and thoracotomy.
PMID- 27500131
TI - Acute Rhabdomyolysis Following Synthetic Cannabinoid Ingestion.
AB - CONTEXT: Novel psychoactive substances, including synthetic cannabinoids, are
becoming increasingly popular, with more patients being seen in the emergency
room following acute ingestion. These substances have been associated with a wide
range of adverse effects. However, identification of complications, clinical
toxicity, and management remain challenging. CASE REPORT: We present the case of
a young African-American male who developed severe agitation and bizarre behavior
following acute K2 ingestion. Laboratory studies revealed markedly elevated serum
creatine phosphokinase (CPK) with normal renal function. The patient was managed
with aggressive intravenous (IV) fluid hydration and treatment of underlying
psychiatric illness. CONCLUSION: We recommend the routine evaluation of renal
function and CPK levels with early initiation of IV hydration among patients who
present to the emergency department following acute ingestion of synthetic
cannabinoids to identify potential complications early as well as institute early
supportive therapy.
PMID- 27500132
TI - Prosthetic Aortic Valve Endocarditis with Left Main Coronary Artery Embolism: A
Case Report and Review of the Literature.
AB - CONTEXT: Coronary embolization is potentially a fatal sequela of endocarditis.
Although the primary cause of acute coronary syndrome is atherosclerotic disease,
it is imperative to consider septic embolism as an etiological factor. CASE
REPORT: Herein, we report a case of ventricular fibrillation and ST-segment
depression myocardial infarction occurring in a patient who initially presented
with fever and increased urinary frequency. Coronary angiography revealed new 99%
occlusion of the left main coronary artery (LMCA). Transesophageal
echocardiography showed bioprosthetic aortic valve with an abscess and
vegetation. Histologic examination of the embolectomy specimen confirmed the
presence of thrombus and Enterococcus faecalis bacteria. Subsequently, the
patient was discharged to the skilled nursing facility in a stable condition
where he completed 6 weeks of intravenous ampicillin. CONCLUSION: We present a
rare case of LMCA embolism due to prosthetic valve endocarditis. The present
report also highlights the diagnostic and therapeutic challenges associated with
such patients.
PMID- 27500133
TI - Electrochemical skin conductance to detect sudomotor dysfunction, peripheral
neuropathy and the risk of foot ulceration among Saudi patients with diabetes
mellitus.
AB - BACKGROUND: Sudomotor dysfunction is manifested clinically as abnormal sweating
leading to dryness of feet skin and increased risk of foot ulceration. The aim of
this study was to test the performance of foot electrochemical skin conductance
(ESC) to detect diabetic peripheral neuropathy and the risk of foot ulceration
against traditional methods in Saudi patients with diabetes mellitus. METHODS:
This cross-sectional study was conducted on 296 Saudi patients with diabetes
mellitus. Painful neuropathic symptoms were evaluated using the neuropathy
symptom score (NSS). The risk of foot ulceration and diabetic peripheral
neuropathy were determined using the neuropathy disability score (NDS). Vibration
perception threshold (VPT) was assessed using neurothesiometer.
Neurophysiological assessment of the right and left sural, peroneal and tibial
nerves was performed in 222 participants. Diabetic peripheral neuropathy was
defined according to the definition of the American Academy of Neurology. ESC was
measured with Sudoscan. RESULTS: Feet-ESC decreased as the scores of sensory and
motor function tests increased. Feet-ESC decreased as the NSS, NDS and severity
of diabetic peripheral neuropathy increased. Sensitivity of feet-ESC < 50MUS to
detect diabetic peripheral neuropathy assessed by VPT >= 25 V, NDS >= 3, NDS >= 6
was 90.1, 61 and 63.8 % respectively and specificity 77, 85 and 81.9 %
respectively. Sensitivity of feet-ESC < 70MUS to detect diabetic peripheral
neuropathy assessed by VPT >= 25 V, NDS >= 3, NDS >= 6 was 100, 80.6 and 80.9 %
respectively. Sensitivity and specificity of feet-ESC < 70MUS to detect confirmed
diabetic peripheral neuropathy were 67.5 and 58.9 % respectively. CONCLUSION:
Sudoscan a simple and objective tool can be used to detect diabetic peripheral
neuropathy and the risk of foot ulceration among patients with diabetes mellitus.
Prospective studies to confirm our results are warranted.
PMID- 27500134
TI - Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic
Oscillation in Cancer.
AB - Circadian rhythms are 24-h oscillations present in most eukaryotes and many
prokaryotes that synchronize activity to the day-night cycle. They are an
essential feature of organismal and cell physiology that coordinate many of the
metabolic, biosynthetic, and signal transduction pathways studied in biology. The
molecular mechanism of circadian rhythm is controlled both by signal transduction
and gene transcription as well as by metabolic feedback. The role of circadian
rhythm in cancer cell development and survival is still not well understood, but
as will be discussed in this Review, accumulated research suggests that circadian
rhythm may be altered or disrupted in many human cancers downstream of common
oncogenic alterations. Thus, a complete understanding of the genetic and
metabolic alterations in cancer must take potential circadian rhythm
perturbations into account, as this disruption itself will influence how gene
expression and metabolism are altered in the cancer cell compared to its non
transformed neighbor. It will be important to better understand these circadian
changes in both normal and cancer cell physiology to potentially design treatment
modalities to exploit this insight.
PMID- 27500135
TI - Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A
Qualitative Evaluation and Systematic Review of Longitudinal and Prospective
Trials.
AB - The Mediterranean-style diet (MedDiet) involves substantial intake of fruits,
vegetables, and fish, and a lower consumption of dairy, red meat, and sugars.
Over the past 15 years, much empirical evidence supports the suggestion that a
MedDiet may be beneficial with respect to reducing the incidence of
cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of
cross-sectional studies that have examined the impact of MedDiet on cognition
have yielded largely positive results. The objective of this review is to
evaluate longitudinal and prospective trials to gain an understanding of how a
MedDiet may impact cognitive processes over time. The included studies were aimed
at improving cognition or minimizing of cognitive decline. Studies reviewed
included assessments of dietary status using either a food frequency
questionnaire or a food diary assessment. Eighteen articles meeting our inclusion
criteria were subjected to systematic review. These revealed that higher
adherence to a MedDiet is associated with slower rates of cognitive decline,
reduced conversion to Alzheimer's disease, and improvements in cognitive
function. The specific cognitive domains that were found to benefit with improved
Mediterranean Diet Score were memory (delayed recognition, long-term, and working
memory), executive function, and visual constructs. The current review has also
considered a number of methodological issues in making recommendations for future
research. The utilization of a dietary pattern, such as the MedDiet, will be
essential as part of the armamentarium to maintain quality of life and reduce the
potential social and economic burden of dementia.
PMID- 27500136
TI - Response to Intravenous Allogeneic Equine Cord Blood-Derived Mesenchymal Stromal
Cells Administered from Chilled or Frozen State in Serum and Protein-Free Media.
AB - Equine mesenchymal stromal cells (MSC) are commonly transported, chilled or
frozen, to veterinary clinics. These MSC must remain viable and minimally
affected by culture, transport, or injection processes. The safety of two carrier
solutions developed for optimal viability and excipient use were evaluated in
ponies, with and without allogeneic cord blood-derived (CB) MSC. We hypothesized
that neither the carrier solutions nor CB-MSC would elicit measurable changes in
clinical, hematological, or biochemical parameters. In nine ponies (study 1), a
bolus of HypoThermosol((r)) FRS (HTS-FRS), CryoStor((r)) CS10 (CS10), or saline
was injected IV (n = 3/treatment). Study 2, following a 1-week washout period, 5
* 10(7) pooled allogeneic CB-MSCs were administered IV in HTS-FRS following 24 h
simulated chilled transport. Study 3, following another 1-week washout period 5 *
10(7) pooled allogeneic CB-MSCs were administered IV in CS10 immediately after
thawing. Nine ponies received CB-MSCs in study 2 and 3, and three ponies received
the cell carrier media without cells. CB-MSCs were pooled in equal numbers from
five unrelated donors. In all studies, ponies were monitored with physical
examination, and blood collection for 7 days following injection. CD4 and CD8
lymphocyte populations were also evaluated in each blood sample. In all three
studies, physical exam, complete blood cell count, serum biochemistry, and
coagulation panel did not deviate from established normal ranges. Proportions of
CD4(+) and CD8(+) lymphocytes increased at 168 h postinjection in CB-MSC
treatment groups regardless of the carrier solution. Decreases in CD4(+/)CD8(+)
double positive populations were observed at 24 and 72 h in CB-MSC-treated
animals. There was no difference in viability between CB-MSCs suspended in HTS
FRS and CS10. HTS-FRS and CS10 used for low volume excipient injection of MSC
suspensions were not associated with short-term adverse reactions. HTS-FRS and
CS10 both adequately maintain CB-MSC viability following hypothermic or frozen
simulated transport, respectively. CB-MSCs do not elicit clinical abnormalities,
but allogeneic stimulation of CD4(+) and CD8(+) lymphocyte populations may occur.
Future studies should include in vitro or in vivo evaluation of cell-mediated or
adaptive immunity to autologous, identical allogeneic, or MSC originating from
additional unrelated individuals in order to better characterize this response.
PMID- 27500138
TI - Techniques and innovations in liver surgery.
PMID- 27500139
TI - How could we image the future in hepatic surgery.
PMID- 27500140
TI - What has changed after the Morioka consensus conference 2014 on laparoscopic
liver resection?
AB - The 2(nd) International Consensus Conference on Laparoscopic Liver Resection
(ICCLLR) was held 4(th)-6(th) October, 2014, in Morioka, Japan. The level of
evidence appears to be low in the field of laparoscopic liver resection (LLR) to
create strong recommendations. Therefore, an independent jury-based consensus
model was applied to better define the current role of LLR and to develop
internationally accepted recommendations. The three-day conference was very
intense with full of insightful discussions on assessment of LLR and its future
directions. The jury drew the statements based on the presentations and documents
prepared by the expert. LLR is theoretically superior to open liver resection
(OLR) because the laparoscope allows better exposure with a magnified view, and
the pneumoperitoneum pressure reduces hepatic vein bleeding from the cut surface.
During the ICCLLR, we shared these theoretical advantages in LLR and the
conceptual change of liver resection. After the ICCLLR, a couple of important
studies have been published to prove this theoretical superiority of LLR over OLR
in short-term outcomes without deteriorating long-term outcomes. Another new
concept was proposed at the ICCLLR: parenchyma sparing (limited) anatomical
resection. Review of the literature supports anatomical resection with parenchyma
sparing strategy for LLR irrespective of hepatocellular carcinoma (HCC) and
colorectal liver metastasis (CRLM). Just after the ICCLLR, sensational news of
clustered mortality after LLR was reported in the Japanese media and they
impacted on daily practice of LLR in Japan. The most important message from the
ICCLLR is to protect patients from this new surgical procedure. The ICCLLR
recommended three actions for the protection of patients: (I) prospective
reporting registry for transparency; (II) a difficulty scoring system to select
patients; (III) creation of a formal structure of education. The online
prospective registry system including items to calculate the difficulty score has
been created in Japan after the ICCLLR for the safe development of LLR.
PMID- 27500137
TI - Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs
and Laying Hens.
AB - Pigs and poultry are by far the most omnivorous of the domesticated farm animals
and it is in their nature to be highly explorative. In the barren production
environments, this motivation to explore can be expressed as abnormal oral
manipulation directed toward pen mates. Tail biting (TB) in pigs and feather
pecking (FP) in laying hens are examples of unwanted behaviors that are
detrimental to the welfare of the animals. The aim of this review is to draw
these two seemingly similar abnormalities together in a common framework, in
order to seek underlying mechanisms and principles. Both TB and FP are affected
by the physical and social environment, but not all individuals in a group
express these behaviors and individual genetic and neurobiological
characteristics play an important role. By synthesizing what is known about
environmental and individual influences, we suggest a novel possible mechanism,
common for pigs and poultry, involving the brain-gut-microbiota axis.
PMID- 27500141
TI - Laparoscopic hepatectomy versus open hepatectomy for colorectal cancer liver
metastases: comparative study with propensity score matching.
AB - BACKGROUND: The objective of this study was to compare the results of
laparoscopic hepatectomy with those of open hepatectomy for colorectal cancer
liver metastases (CCLM) using a propensity score matching (PSM) in two university
hospital settings. METHODS: A patient in the laparoscopic approach (LA) surgery
group was randomly matched with another patient in the open approach (OA) group
using a 1:1 allocated ratio with the nearest estimated propensity score. No
patients of the LA group were excluded for the matching. Matching criteria
included age, gender, body mass index (BMI), American society anesthesiologists
score, potential co-morbidities, hepatopathies, synchronous or metachronous
lesions, size and number of CCLM, preoperative chemotherapy, minor or major liver
resections. Intraoperative, postoperative data, and survival were compared in
both groups. RESULTS: From January 2012 to January 2015, a total of 242
hepatectomies were consecutively performed, of which 119 for CCLM, namely 101 in
the OA group (84.9%) and 18 in the LA group (15.1%). The conversion rate was 5.6%
(n=1). The mortality rate was 1% in the OA group and 0% in the LA group. Prior to
PSM, there was a statistically significant difference favorable to the LA group
regarding operative time, blood loss, length of hospital stay and the rate of
medical complications. After PSM, there was no difference regarding operative
time or length of hospital stay. However, there was a trend towards less blood
loss (P=0.066) and fewer medical complications (44.4% vs.16.7%, P=0.07). The R0
resection rate was 94.4% (n=17) in the two groups. In addition, there was no
difference regarding overall survival (P=0.358) and recurrence-free survival [HR
=0.99 (0.1-12.7); P=0.99]. CONCLUSIONS: Laparoscopic liver resections for CCLM
seem to yield short- and long-term results, which are similar to open
hepatectomies, and could well be considered an alternative to open surgery and
become the gold standard in carefully selected patients.
PMID- 27500143
TI - Robotic liver surgery: technical aspects and review of the literature.
AB - Minimally invasive surgery for liver resections has a defined role and represents
an accepted alternative to open techniques for selected cases. Robotic technology
can overcome some of the disadvantages of the laparoscopic technique, mainly in
the most complex cases. Precise dissection and microsuturing is possible, even in
narrow operative fields, allowing for a better dissection of the hepatic hilum,
fine lymphadenectomy, and biliary reconstruction even with small bile ducts and
easier bleeding control. This technique has the potential to allow for a greater
number of major resections and difficult segmentectomies to be performed in a
minimally invasive fashion. The implementation of near-infrared fluorescence with
indocyanine green (ICG) also allows for a more accurate recognition of vascular
and biliary anatomy. The perspectives of this kind of virtually implemented
imaging are very promising and may be reflected in better outcomes. The overall
data present in current literature suggests that robotic liver resections are at
least comparable to both open and laparoscopic surgery in terms of perioperative
and postoperative outcomes. This article provides technical details of robotic
liver resections and a review of the current literature.
PMID- 27500142
TI - Short and long-term outcomes of laparoscopic compared to open liver resection for
colorectal liver metastases.
AB - BACKGROUND: Minimally invasive surgery (MIS) is now established as standard of
care for a variety of gastrointestinal procedures for benign and malignant
indications. However, due to concerns regarding superiority to open liver
resection (OLR), the uptake of laparoscopic liver resection (LLR) has been slow.
Data on long-term outcomes of LLR for colorectal liver metastases (CRLM) remain
limited. We conducted a systematic review and meta-analysis of short and long
term outcomes of LLR compared to OLR for CRLM. METHODS: Five electronic databases
were systematically searched for studies comparing LLR and OLR for CRLM and
reporting on survival outcomes. Two reviewers independently selected studies and
extracted data. Primary outcomes were overall survival (OS) and recurrence free
survival (RFS). Secondary outcomes were operative time, estimated blood loss,
post-operative major morbidity, mortality, length of stay (LOS), and resection
margins. RESULTS: Eight non-randomized studies (NRS) were included (n=2,017 total
patients). Six were matched cohort studies. LLR reduced estimated blood loss
[mean difference: -108.9; 95% confidence interval (CI), -214.0 to -3.7) and major
morbidity [relative risk (RR): 0.68; 95% CI, 0.56-0.83], but not mortality. No
difference was observed in operative time, LOS, resection margins, R0 resections,
and recurrence. Survival data could not be pooled. No studies reported inferior
survival with LLR. OS varied from 36% to 60% for LLR and 37% to 65% for OLR. RFS
ranged from 14% to 30% for LLR and 22% to 38% for OLR. According to the grade
classification, the strength of evidence was low to very low for all outcomes.
The use of parenchymal sparing resections with LLR and OLR could not be assessed.
CONCLUSIONS: Based on limited retrospective evidence, LLR offers reduced
morbidity and blood loss compared to OLR for CRLM. Comparable oncologic outcomes
can be achieved. Although LLR cannot be considered as standard of care for CRLM,
it is beneficial for well-selected patients and lesions. Therefore, LLR should be
part of the liver surgeon's armamentarium.
PMID- 27500144
TI - Clinical application of indocyanine green-fluorescence imaging during
hepatectomy.
AB - In hepatobiliary surgery, the fluorescence and bile excretion of indocyanine
green (ICG) can be used for real-time visualization of biological structure.
Fluorescence cholangiography is used to obtain fluorescence images of the bile
ducts following intrabiliary injection of 0.025-0.5 mg/mL ICG or intravenous
injection of 2.5 mg ICG. Recently, the latter technique has been used in
laparoscopic/robotic cholecystectomy. Intraoperative fluorescence imaging can be
used to identify subcapsular hepatic tumors. Primary and secondary hepatic
malignancy can be identified by intraoperative fluorescence imaging using
preoperative intravenous injection of ICG through biliary excretion disorders
that exist in cancerous tissues of hepatocellular carcinoma (HCC) and in non
cancerous hepatic parenchyma around adenocarcinoma foci. Intraoperative
fluorescence imaging may help detect tumors to be removed, especially during
laparoscopic hepatectomy, in which visual inspection and palpation are limited,
compared with open surgery. Fluorescence imaging can also be used to identify
hepatic segments. Boundaries of hepatic segments can be visualized following
injection of 0.25-2.5 mg/mL ICG into the portal veins or by intravenous injection
of 2.5 mg ICG following closure of the proximal portal pedicle toward hepatic
regions to be removed. These techniques enable identification of hepatic segments
before hepatectomy and during parenchymal transection for anatomic resection.
Advances in imaging systems will increase the use of fluorescence imaging as an
intraoperative navigation tool that can enhance the safety and accuracy of open
and laparoscopic/robotic hepatobiliary surgery.
PMID- 27500145
TI - High intensity focused ultrasound (HIFU) applied to hepato-bilio-pancreatic and
the digestive system-current state of the art and future perspectives.
AB - BACKGROUND: High intensity focused ultrasound (HIFU) is emerging as a valid
minimally-invasive image-guided treatment of malignancies. We aimed to review to
current state of the art of HIFU therapy applied to the digestive system and
discuss some promising avenues of the technology. METHODS: Pertinent studies were
identified through PubMed and Embase search engines using the following keywords,
combined in different ways: HIFU, esophagus, stomach, liver, pancreas,
gallbladder, colon, rectum, and cancer. Experimental proof of the concept of
endoluminal HIFU mucosa/submucosa ablation using a custom-made transducer has
been obtained in vivo in the porcine model. RESULTS: Forty-four studies reported
on the clinical use of HIFU to treat liver lesions, while 19 series were found on
HIFU treatment of pancreatic cancers and four studies included patients suffering
from both liver and pancreatic cancers, reporting on a total of 1,682 and 823
cases for liver and pancreas, respectively. Only very limited comparative
prospective studies have been reported. CONCLUSIONS: Digestive system clinical
applications of HIFU are limited to pancreatic and liver cancer. It is safe and
well tolerated. The exact place in the hepatocellular carcinoma (HCC) management
algorithm remains to be defined. HIFU seems to add clear survival advantages over
trans arterial chemo embolization (TACE) alone and similar results when compared
to radio frequency (RF). For pancreatic cancer, HIFU achieves consistent cancer
related pain relief. Further research is warranted to improve targeting accuracy
and efficacy monitoring. Furthermore, additional work is required to transfer
this technology on appealing treatments such as endoscopic HIFU-based therapies.
PMID- 27500146
TI - Laparoscopic Pringle maneuver: how we do it?
AB - Laparoscopic liver resection (LLR) is technically possible with new devices which
allow a relatively bloodless liver parenchymal transection. Despite, the main
concern remains intraoperative hemorrhage. Currently, perioperative excessive
blood loss during LLR is difficult to control with necessity of laparotomy
conversion. Moreover, major blood loss requires transfusion and increases
postoperative morbidity and mortality. When in-flow is limited by the hepatic
pedicle clamping, it reduces intraoperative blood loss. The Pringle maneuver,
first described in 1908, is the simplest method of inflow occlusion and currently
can be achieved during LLR. The purpose of this note was to describe two
different modalities of Pringle maneuver used by two different teams during LLR.
PMID- 27500147
TI - Combined liver and extrahepatic bile duct resection for biliary invasion of
colorectal metastasis: a case-cohort analysis and systematic review.
AB - BACKGROUND: Colorectal liver metastases (CRLMs) with biliary invasion can be
treated with a combined liver and extrahepatic bile duct resection. The aim of
this study was to analyze outcomes of this procedure in a case-cohort analysis
and systematic review. METHODS: Consecutive patients who underwent a major liver
resection for CRLM between 2003 and 2013 were selected from a single center
prospective database, comparing patients with and without biliary invasion. A
specific and a general search strategy were used to identify relevant articles in
the systematic review. RESULTS: Ten patients (13.2%) underwent combined liver and
extrahepatic bile duct resection for CLRM with biliary invasion, among 76
patients included. An R0 resection was achieved in five of ten patients (50%);
one of ten patients died postoperatively. Median overall survival was 19 months
among patients with biliary invasion, versus 106 months among patients without
biliary invasion (P=0.12). The systematic review yielded a large variability in 5
year survival after resection of CLRM with biliary invasion, ranging between 33
80%. CONCLUSIONS: Surgical resection of CLRM with central biliary invasion is
feasible, but survival in these patients tends to be lower due to a high rate of
non-radical resections.
PMID- 27500149
TI - Twenty years of Milan criteria: the wicked flee though no one pursues.
PMID- 27500148
TI - Nutrition assessment and its effect on various clinical variables among patients
undergoing liver transplant.
AB - BACKGROUND: Malnutrition is highly prevalent in patients undergoing liver
transplantation and has been associated to various clinical variables and outcome
of the surgery. METHODS: We recruited 54 adult patients undergoing living donor
liver transplant (LT) as study sample. Nutrition assessment was performed by body
mass index (BMI), BMI for ascites, albumin, subjective global assessment (SGA)
and anthropometry [mid upper arm circumference (MUAC), mid arm muscle
circumference (MAMC), and triceps skin-fold (TSF)], Hand Grip strength, and phase
angle of the body. Prevalence and comparison of malnutrition was performed with
various clinical variables: aetiology, Child Turcotte Pugh scores and model for
end stage liver disease (ESLD) grades, degree of ascites, blood product usage,
blood loss during the surgery, mortality, days [intensive care unit (ICU),
Ventilator and Hospital], and Bio-impedance analysis [weight, fat mass, fat free
mass (FFM), muscle mass and body fat%]. RESULTS: Assessment of nutrition status
represents a major challenge because of complications like fluid retention,
hypoalbuminemia and hypoproteinemia. Different nutrition assessment tools show
great disparity in the level of malnutrition among ESLD patients. In the present
study recipient nutrition status evaluation by different nutrition assessment
tools used showed malnutrition ranging from 3.7% to 100%. BMI and anthropometric
measurements showed lower prevalence of malnutrition than phase angle and SGA
whereas hand grip strength showed 100% malnutrition. Agreement among nutrition
assessment methods showed moderate agreement (kappa=0.444) of SGA with phase
angle of the body. Malnutrition by different assessment tools was significantly
associated to various clinical variables except MELD and days (ICU, Ventilator
and Hospital). SGA was significantly (P<0.05) associated to majority of the
clinical variables like aetiology, child Turcotte Pugh grades, degree of ascites,
blood product usage, blood loss during the surgery, BIA (fat mass, FFM, muscle
mass and body fat%). CONCLUSIONS: The different nutrition assessment tools showed
great variability of results. SGA showed moderate agreement with phase angle of
the body and was associated with various clinical and prognostic variables of
liver transplantation.
PMID- 27500150
TI - A totally laparoscopic associating liver partition and portal vein ligation for
staged hepatectomy assisted with radiofrequency (radiofrequency assisted liver
partition with portal vein ligation) for staged liver resection.
AB - In order to induce liver hypertrophy to enable liver resection in patients with a
small future liver remnant (FLR), various methods have been proposed in addition
to portal vein embolisation (PVE). Most recently, the associating liver partition
and portal vein ligation for staged hepatectomy (ALPPS) technique has gained
significant international interest. This technique is limited by the high
morbidity associated with an in situ liver splitting and the patient undergoing
two open operations. We present the case of a variant ALPPS technique performed
entirely laparoscopically with no major morbidity or mortality. An increased
liver volume of 57.9% was seen after 14 days. This technique is feasible to
perform and compares favourably to other ALPPS methods whilst gaining the
advantages of laparoscopic surgery.
PMID- 27500151
TI - Gastrointestinal stromal tumor as cause of hepatic mass.
PMID- 27500152
TI - Evidence and pitfalls in diagnosis and prognostication of acute coronary
syndrome.
PMID- 27500153
TI - Predictive significance of detectable cardiac troponin I measured with a
contemporary-sensitive assay in a real life experience.
AB - BACKGROUND: Cardiac troponin (cTn) testing has reduced the likelihood of
erroneous discharge of patients with acute coronary syndrome (ACS) from the
emergency department (ED), but doubts remain about optimal clinical use. This
study was planned for evaluating the predictive significance of cTn values
between the limit of detection of the method and the 99th percentile in ED
patients evaluated for suspected ACS. METHODS: In this retrospective study all
hospital records of patients admitted over a 6-month period to the ED and with at
least one cTnI value comprised between the limit of detection (0.01 ng/mL) and
the 99th percentile of the assay (0.05 ng/mL) were analyzed. RESULTS: A total of
4,749 patients with cTnI value between 0.01-0.05 ng/mL were identified among
57,879 ED visits throughout the study period. Overall, 2,189 patients (46.1%)
were discharged from the ED, 2,529 (53.25%) were admitted to the hospital and 31
(0.65%) died during ED stay. A total number of 289 patients out of 2,189 who were
discharged (i.e., 13.2%) had additional ED visits within 30 days. Among these, 6
were diagnosed with ACS, representing 0.27% of patients discharged [negative
predictive value (NPV) 0.997; 95% CI, 0.994-0.999] and 2.1% of those with second
admission (NPV 0.979; 95% CI, 0.955-0.992). Only one of the 2,529 patients
admitted to the hospital (i.e., 0.04%) developed an ACS during hospital stay.
CONCLUSIONS: The results of our retrospective study suggest that the suitability
of using a contemporary-sensitive cTnI immunoassay assay in the context of an
appropriate protocol represents a safe and effective strategy for ruling in and
ruling out ACS in patients presenting to the ED.
PMID- 27500154
TI - Impact of gestational risk factors on maternal cardiovascular system.
AB - BACKGROUND: Scarce evidence is available on the potential cardiovascular
abnormalities associated with some common gestational complications. We aimed to
analyze the potential maternal cardiac alterations related to gestational
complications, including body mass index (BMI) >25 kg/m(2), gaining excessive
weight, or developing antenatal depression. METHODS: The design of this study was
a secondary analysis of a randomized controlled trial. Echocardiography was
performed to assess cardiovascular indicators of maternal hemodynamic, cardiac
remodeling and left ventricular (LV) function in 59 sedentary pregnant women at
20 and 34 weeks of gestation. RESULTS: Starting pregnancy with a BMI >25 kg/m(2),
gaining excessive weight, and developing antenatal depression had no
cardiovascular impact on maternal health (P value >0.002). Depressed women were
more likely to exceed weight gain recommendations than non-depressed women (P
value <0.002). CONCLUSIONS: The evaluated gestational complications seem not to
induce cardiovascular alterations in hemodynamic, remodeling and LV function
indicators. However, developing antenatal depression increases the risk of an
excessive weight gain. This finding is potentially important because excessive
weight gain during pregnancy associates with a higher risk of cardiovascular
diseases (CVD) later in life.
PMID- 27500155
TI - Red blood cell distribution width independently predicts medium-term mortality
and major adverse cardiac events after an acute coronary syndrome.
AB - BACKGROUND: The value of red blood cell distribution width (RDW), a simple and
inexpensive measure of anisocytosis, has been associated with the outcome of many
human chronic disorders. Therefore, this retrospective study was aimed to
investigate whether RDW may be associated with medium-term mortality and major
adverse cardiac events (MACE) after an acute coronary syndrome (ACS). METHODS: A
total number of 979 patients diagnosed with ACS were enrolled from June 2014 to
November 2014, and followed-up until June 2015. RESULTS: The RDW value in
patients with 3-month MACE and in those who died was significantly higher than
that of patients without 3-month MACE (13.3% vs. 14.0%; P<0.001) and those who
were still alive at the end of follow-up (13.4% vs. 14.4%; P<0.001). In
univariate analysis, RDW was found to be associated with 3-month MACE [odds ratio
(OR), 1.70; 95% CI, 1.44-2.00, P<0.001]. In multivariate analysis, RDW remained
independently associated with 3-month MACE (adjusted OR, 1.36; 95% CI, 1.19-1.55;
P<0.001) and death (adjusted OR, 1.34; 95% CI, 1.05-1.71; P=0.020). The accuracy
of RDW for predicting 3-month MACE was 0.67 (95% CI, 0.66-0.72; P<0.001). The
most efficient discriminatory RDW value was 14.8%, which was associated with 3.8
(95% CI, 2.6-5.7; P<0.001) higher risk of 3-month MACE. Patients with RDW >14.8%
exhibited a significantly short survival than those with RDW <=14.8% (331 vs. 465
days; P<0.001). CONCLUSIONS: The results of this study confirm that RDW may be a
valuable, easy and inexpensive parameter for stratifying the medium-term risk in
patients with ACS.
PMID- 27500156
TI - Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance
(CMR) imaging in the assessment of patients presenting with chest pain suspected
for acute coronary syndrome.
AB - Acute chest pain is an important clinical challenge and a major reason for
presentation to the emergency department. Although multiple imaging techniques
are available to assess patients with suspected acute coronary syndrome (ACS),
considerable interest has been focused on the use of non-invasive imaging options
as coronary computed tomography angiography (CCTA) and cardiac magnetic resonance
(CMR). According to several recent evidences, CCTA has been shown to represent a
useful tool to rapidly and accurately diagnose coronary artery disease (CAD) in
patients with low to intermediate cardiovascular risk. CCTA examination has the
unique ability to non-invasively depict the coronary anatomy, not only allowing
visualization of the lumen of the arteries in order to detect severe stenosis or
occlusion responsible of myocardial ischemia, but also allows the assessment of
coronary artery wall by demonstrating the presence or absence of CAD. However,
routine CCTA is not able to differentiate ischemic from non-ischemic chest pain
in patients with known CAD and it does not provide any functional assessment of
the heart. Conversely, CMR is considered the gold standard in the evaluation of
morphology, function, viability and tissue characterization of the heart. CMR
offers a wide range of tools for diagnosing myocardial infarction (MI) at least
at the same time of the elevation of cardiac troponin values, differentiating
infarct tissue and ischemic myocardium from normal myocardium or mimicking
conditions, and distinguishing between new and old ischemic events. In high-risk
patients, with acute and chronic manifestations of CAD, CMR may be preferable to
CCTA, since it would allow detection, differential diagnosis, prognostic
evaluation and management of MI.
PMID- 27500157
TI - Epidemiology of coronary heart disease and acute coronary syndrome.
AB - The aim of this review is to summarize the incidence, prevalence, trend in
mortality, and general prognosis of coronary heart disease (CHD) and a related
condition, acute coronary syndrome (ACS). Although CHD mortality has gradually
declined over the last decades in western countries, this condition still causes
about one-third of all deaths in people older than 35 years. This evidence, along
with the fact that mortality from CHD is expected to continue increasing in
developing countries, illustrates the need for implementing effective primary
prevention approaches worldwide and identifying risk groups and areas for
possible improvement.
PMID- 27500158
TI - High-sensitivity cardiac troponin testing in routine practice: economic and
organizational advantages.
AB - Very seldom, if ever, a single laboratory test has provided such a paradigm shift
in the managed care as cardiac troponin (cTn) testing. More than twenty years of
improvements in test design and analytical features have contributed to
revolutionize the clinical recommendations and guidelines, and the diagnosis of
myocardial infarction (MI) is now highly dependent upon the kinetics of cTn
within a suggestive clinical setting. Despite the advent of high-sensitivity cTn
(HS-cTn) immunoassays has allowed a more accurate and timely diagnosis as well as
a higher prognostic accuracy, the focus is now shifting on the most suitable
algorithms and on a comprehensive approach to the clinical management of acute
coronary syndrome (ACS). In this article we aim to discuss the implications of HS
cTn testing for ruling out and ruling in ACS. In the latter instance, main
improvements are related to ACS diagnosis in women, in whom this pathology is
still often underdiagnosed or misdiagnosed. A quick and accurate rule out will
also regarded as a great advantage from both an organizational and economic
standpoint. The advantages that will stem from this new approach have been
recently assessed, and shortening of repeated testing 1 or 2 h from conventional
algorithms entailing blood sampling at 3 and 6 h seems attainable. The larger
benefits will definitely occur in clinical settings where the actual diagnosis
rate of MI among patients with suspect ACS is lower and, consequently, the
negative predictive value (NPV) of HS-cTn is the highest.
PMID- 27500159
TI - Prognostic biomarkers in acute coronary syndrome.
AB - The acute coronary syndrome (ACS) is a leading cause of death around the globe.
Beside a still high mortality rate, additional complications of ACS include
arrhythmias, left ventricular mural thrombus, cardiac fibrosis, heart failure
(HF), cardiogenic shock, mitral valve dysfunction, aneurysms, up to cardiac
rupture. Despite many prognostic tools have been developed over the past decades,
efforts are still ongoing to identify reliable and predictive biomarkers, which
may help predict the prognosis of these patients and especially the risk of HF.
Recent evidence suggests that the value of a discrete number of biomarkers of
myocardial fibrosis, namely the soluble form of suppression of tumorigenicity 2
(sST2) and galectin-3 (GAL-3), may be predictive of HF and death in patients with
ACS. Interestingly, the already promising predictive value of these biomarkers
when measured alone was shown to be consistently magnified when combined with
other and well-established cardiac biomarkers such natriuretic peptides and
cardiac troponins. This article is hence aimed to review the current knowledge
about cardiac biomarkers of fibrosis and adverse remodeling.
PMID- 27500160
TI - Echocardiographic assessment of myocardial ischemia.
AB - Over the last 60 years, echocardiography has emerged as a dominant and
indispensable technique for the detection and assessment of coronary heart
disease (CHD). In this review, we will describe and discuss this powerful tool of
cardiology, especially in the hands of an experienced user, with a focus on
myocardial ischemia. Technical development is still on-going, and various new
ultrasound techniques have been established in the field of echocardiography in
the last several years, including tissue Doppler imaging (TDI), contrast
echocardiography, three-dimensional echocardiography (3DE), and speckle tracking
echocardiography (i.e., strain/strain rate-echocardiography). High-end equipment
with harmonic imaging, high frame rates and the opportunity to adjust mechanical
indices has improved imaging quality. Like all new techniques, these techniques
must first be subjected to comprehensive scientific assessment, and appropriate
training that accounts for physical and physiological limits should be provided.
These limits will constantly be redefined as echocardiographic techniques
continue to change, which will present new challenges for the further development
of ultrasound technology.
PMID- 27500161
TI - The Popeye Domain Containing Genes and cAMP Signaling.
AB - 3'-5'-cyclic adenosine monophosphate (cAMP) is a second messenger, which plays an
important role in the heart. It is generated in response to activation of G
protein-coupled receptors (GPCRs). Initially, it was thought that protein kinase
A (PKA) exclusively mediates cAMP-induced cellular responses such as an increase
in cardiac contractility, relaxation, and heart rate. With the identification of
the exchange factor directly activated by cAMP (EPAC) and hyperpolarizing cyclic
nucleotide-gated (HCN) channels as cAMP effector proteins it became clear that a
protein network is involved in cAMP signaling. The Popeye domain containing
(Popdc) genes encode yet another family of cAMP-binding proteins, which are
prominently expressed in the heart. Loss-of-function mutations in mice are
associated with cardiac arrhythmia and impaired skeletal muscle regeneration.
Interestingly, the cardiac phenotype, which is present in both, Popdc1 and Popdc2
null mutants, is characterized by a stress-induced sinus bradycardia, suggesting
that Popdc proteins participate in cAMP signaling in the sinuatrial node. The
identification of the two-pore channel TREK-1 and Caveolin 3 as Popdc-interacting
proteins represents a first step into understanding the mechanisms of heart rate
modulation triggered by Popdc proteins.
PMID- 27500162
TI - Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs
Drosophila Heart Structure and Impairs Function.
AB - Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps
maintain protein homeostasis in all cells and serves specialized functions in
distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis
and atrophy. However, little is known about VCP's role(s) in the heart. Its
functional diversity is determined by differential binding of distinct
cofactors/adapters, which is likely disrupted during disease. VCP mutations cause
multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that
involves inclusion body myopathy. MSP patients display progressive muscle
weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory
failure, which are consistent with critical myocardial roles for the enzyme.
Nonetheless, efficient models to interrogate VCP in cardiac muscle remain
underdeveloped and poorly studied. Here, we investigated the significance of VCP
and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated
knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar
organization and heart function in adult flies. Furthermore, expression of MSP
disease-causing alleles engendered cardiomyopathy in adults and structural
defects in embryonic hearts. Drosophila may therefore serve as a valuable model
for examining role(s) of VCP in cardiogenesis and for identifying novel heart
specific VCP interactions, which when disrupted via mutation, contribute to or
elicit cardiac pathology.
PMID- 27500163
TI - Investigating the Impact of Preparation Strategies on USMLE Step 1 Performance.
AB - BACKGROUND: The USMLE Step 1 score helps differentiate applicants for competitive
residency programs. Students frequently ask medical educators how to prepare for
this high-stakes exam. Multiple resources exist such as books, training programs,
and question banks. The purpose of this study is to provide medical educators
with data on which resources correlate with higher exam scores. METHODS: 164
medical students at West Virginia University School of Medicine were given a
survey following the completion of Step 1. The survey contained questions about
resources used and exam date. De-identified data was paired with class quartile
rankings and Step 1 scores. Average Step 1 scores were calculated for each
resource and a student's t-test was used to compare between groups. Test dates
were also broken into quintiles and average Step 1 scores were compared between
groups. RESULTS: Students who used the USMLE World question bank had higher Step
1 scores (M=229, SE=1.4) compared to students who did not use this resource
(M=215, SE=4.2). Commercial preparation courses were not associated with improved
scores. The timing of when the exam was taken was also not associated with
significant differences between scores. CONCLUSIONS: Interactive study options
offer the best choice to improve USMLE Step 1 scores.
PMID- 27500164
TI - Evaluation of the knowledge level of health violations in food production,
distribution, sales centers and public places and their authorities investigating
among the women of Bushehr city.
AB - BACKGROUND: Women and mothers are the most important educational audience to
convey health teachings. This study was aimed to evaluate the knowledge level of
different types of health violations of food production, distribution, sale
centers and public places; and authorities investigating the violations among
women referring to health care centers in Bushehr. MATERIALS AND METHODS: In this
descriptive-analytical study, which was done cross-sectionally, 600 women who
were referred to health care centers affiliated to the Bushehr University of
Medical Sciences was selected by convenience sampling. Two-part questionnaire was
used to collect data: demographic information and a researcher-designed knowledge
survey questionnaire consisted of 25 questions with Cronbach's alpha = 0.7. Data
were analyzed with the software SPSS version 13; using Chi-square test and Phi
and Cramer test. P <= 0.05 was considered to be statistically significant.
RESULTS: The findings showed that 56.9% and 26.5% of women had good and moderate
knowledge levels regarding health violations, while the general knowledge level
of authorities investigating health violations were at the moderate level among
57.3% and at the good level among 15.3% of women. Overall, there was a
significant relationship between education level and the women's knowledge level
of health violations (P < 0.0001). The relationship between the women's education
level and authorities investigating health violations was not significant (P =
0.073). CONCLUSION: Applying interventional methods of education in health
violations to the women by health centers can elevate the level of health
knowledge among them.
PMID- 27500165
TI - Assessment of knowledge, attitude, and practice with regard to evidence-based
dentistry among dental students in Isfahan University of Medical Sciences.
AB - AIM: Evidence-based dentistry (EBD) is an approach to oral health that requires
the application and examination of relevant scientific data related to the
patient's oral health and his priorities. The aim of this study was to assess
knowledge, attitude, and practice of dental students of Isfahan about EBD.
MATERIALS AND METHODS: In this descriptive study, 168 dental students in 3 final
years of their education who engaged in clinical practice by consensus sampling
were recruited. For data collection, a validated questionnaire was used. The
questionnaire was consisted of demographic questions and some questions about
four issues: Knowledge of self-assess (KSA), evidence-based practice, actual
knowledge and attitude about EBD. Data were analyzed with t-test, one-way ANOVA,
Chi-square, and linear regression with SPSS 16. RESULTS: One hundred and thirty
six students from 168 students were filled the questionnaire. The mean of KSA was
13 +/- 4.3, mean of usage of useful references in EBD was 16.9 +/- 7.6. One-third
of students were studied their last article in last 6 months before. The mean of
actual knowledge and attitude was 7.4 +/- 2.3 and 24 +/- 3.8, respectively. The
relation between 4 main issues was significant (P < 0.05). CONCLUSION: By
considering overall interest and positive attitude toward learning EBD in dental
students, it is highly recommended that practical educational courses about EBD
be planned by dental faculties.
PMID- 27500166
TI - Factors affecting tea consumption pattern in an urban society in Isfahan, Iran.
AB - OBJECTIVE: To determine the tea consumption pattern in an urban society in
Isfahan. METHODS: A descriptive, cross-sectional survey was carried out using
questioner among 664 households who were selected by two steps cluster sampling.
A questionnaire was developed including demographic questions, information on the
quantity of tea intake by every member of the family, tea type, and tea brand
preference. RESULTS: The individuals who prioritized black tea as their 1(st)
choice were 90.1% of the total surveyed community. The average amount of tea
consumed was calculated as 1243 +/- 530 ml/day. The individuals who were between
36 and 45 and <15 years old were shown as the highest and the lowest tea
consumers, respectively. Men significantly consumed more amount of tea than women
did and married participants significantly used more amount of tea than singles
(P < 0.05). The number of the family members, though, had no impact on tea
consumption (P > 0.05). Brand preference of tea showed that the individuals who
prioritized Ahmed brand as their 1(st) choice constituted 44% of the total
participants. CONCLUSION: Tea consumption pattern in an Iranian sample is
specific. Despite of the huge evidence on the green tea benefits, this type of
tea has very low popularity and among the available black tea brands, the
imported ones are the most preferred.
PMID- 27500167
TI - The barriers to the application of the research findings from the nurses'
perspective: A case study in a teaching hospital.
AB - BACKGROUND: The application of the nursing research findings is one of the most
important indicators of development in the nursing profession, which leads to
providing efficient and effective patient care and improving the quality of
nursing care. According the result of some studies, transferring the evidence
based findings to the nurses' practice and education in the world has been slow
and sometimes unsuccessful. This study aimed to investigate the most important
barriers to the application of research findings from the nurses' perspective.
MATERIALS AND METHODS: This cross-sectional study conducted on a sample of 210
nurses in a teaching hospital in Tehran in 2013. The data were collected using a
researcher-made questionnaire consisted of two parts, including items about
nurses' demographic characteristics and 30 items to identify the most important
barriers to the application of research findings from the studied nurses'
perspective. RESULTS: "The lack of sufficient time for reading the studies," "the
lack of sufficient time to implement the new ideas," "the lack of adequate
facilities to implement the ideas," "nurses' little interest in conducting
studies," and "the lack of authority to change the methods and patterns of care"
with, respectively, 85%, 84.6%, 83.8%, 83.4%, and 80.5% agreement with the
existence of barriers were the most barriers to application of research findings
from the studied nurses' perspective. CONCLUSION: The lack of time was the most
important barrier to the use of research findings from the perspective of studied
nurses. Therefore, some effective strategies should be used by hospital managers
and health policy makers to overcome this barrier. Some of these strategies can
be employing new personnel and hiring skilled and efficient human resources in
order to decrease the workload of nurses, organizing the nurses' work shifts,
providing right balance between patients and nurses in the wards, etc.
PMID- 27500168
TI - Performance evaluation of Iranian cooling vest on the physiological indices in
hot climatic chamber.
AB - BACKGROUND: Heat stress is a threat to those who work in high temperatures. The
purpose in this study was an examination of the cooling ability of Iranian phase
change material (PCM) cold vest in hot and dry conditions in a climatic chamber.
MATERIALS AND METHODS: This experimental study was implemented on 12 male
students (age 23.7 +/- 2.8 years, weight 66.1 +/- 11.4 kg, and VO2 max 2.53
L/min) in 2013. The heat strain score index (HSSI), skin temperature and oral
temperature, and heartbeat in two phases with and without cooling vest was
measured during 30 min in a climatic chamber (temperature 38.8 +/- 1.3 degrees C
humidity ratio 32.9 +/- 2.3%) and in two activity intensity of 2.4 and 4.8 km/h
speed on the treadmill, and the data differences between groups "with" and
"without" vest were tested by t-test and repeated measurement. The level of
significance was considered as 0.05. RESULTS: The change in heartbeat at two
activities, the oral temperature and heat strain score at 4.8 km/h, did not
differ significantly between groups (with and without vest), as expected (P >
0.05). However, the change in skin temperature at two activities, oral
temperature and heat strain score at 2.4 km/h, was significant between groups, as
expected (P < 0.05). The average of skin temperature at 15(th) and 30(th) min
during the experiment at two activities of 2.4 and 4.8 km/h was significant.
CONCLUSION: The findings of the study indicated that using the Iranian PCM cold
vest in hot and dry climate can affect the reduction of skin temperature, oral
temperature, and HSSI in light activities.
PMID- 27500169
TI - Acceptance and satisfaction of parents and students about a school-based dietary
intervention in Isfahan, 2012-2013.
AB - OBJECTIVE: Snacks play an important role in child health and nutritional status.
Schools are considered as the preferred place to encourage healthy eating among
children. The aim of this study was to evaluate the effect of buffet school-based
intervention on acceptance and satisfaction of parents and students in Iran.
MATERIALS AND METHODS: Primary school students (n = 1120, 68.83% girls) from
first to third grade, with one of their parents, participated in this prospective
field trial study conducted in Isfahan, Iran. The study was consisted of three
phases; schools selection, kitchen selection, implementation including two
different parts, getting order and distribution. We provided hot snacks as
traditional and healthy fast food according to taste and food preferences of
children. Acceptance and satisfaction of parents and students were evaluated via
a researcher made questionnaire before and after the intervention in one-third of
participants as a representative sample of students who ordered the snacks.
RESULTS: Most of the students usually ate snack in the break-time at school, the
eagerness of provided snacks was 98.8% and 63.6% in girls and boys, respectively.
The most interesting tastes were Ashe Reshteh and Tahchin, (45.1% girls vs. 36.8%
boys), while bean (among girls) and Ashe Jo (among boys) were ranked as the
lowest. More than half of parents (66.7%) evaluated the price of snacks as
"acceptable," showing their satisfaction. CONCLUSION: Results of this study
indicate that school-based interventions accompanied with parental and
principals' support is considered as a practical approach to promote healthful
eating at an early age. Developing effective interventions for youth might,
therefore, help to prevent unhealthy dietary choices becoming habitual.
PMID- 27500170
TI - Students' perceptions on feedback module in pharmacology.
AB - CONTEXT: Feedback is an integral part of formative assessment though
underutilized in medical education. The objective of this study was to review our
feedback module through students' perceptions. METHODOLOGY: We have developed a
feedback module which is practiced by us for last 10 years for term ending
examination that gives collective feedback to the whole class, followed by
individual student-teacher interactions. Students were also exposed to 6-7
multiple choice questions (MCQs) based assessment during the course of
pharmacology. Immediately after each MCQ test the answer keys is displayed along
with an explanation. Two classes of students were requested to give their
perceptions about the feedback by responding on Likert scale for the statements
in the questionnaire. All the 206 students who volunteered for the study were
enrolled in the study. Mann-Whitney test was used to calculate the difference in
perceptions. RESULTS: Of 278 students of two classes, 206 responded (74%).
Students' agreement varied from 93% to 98% for 5 items in the questionnaire for
the feedback after term ending examinations. Perception of students attending one
or more than one feedback session did not differ significantly. For MCQs, tests
agreement was 91% to 98% for the 4 items. There was no significant difference
between two classes in their perceptions regarding feedback practices (P < 0.05).
CONCLUSION: Students gave a favorable opinion for our feedback module. In the
medical colleges with a large number of students, this module is feasible for
feedback in formative assessment in the form of written tests.
PMID- 27500171
TI - Validation of a questionnaire to measure sexual health knowledge and
understanding (Sexual Health Questionnaire) in Nepalese secondary school: A
psychometric process.
AB - BACKGROUND: School-based sex education has the potential to prevent unwanted
pregnancy and to promote positive sexual health at the individual, family and
community level. OBJECTIVES: To develop and validate a sexual health
questionnaire to measure young peoples' sexual health knowledge and understanding
(SHQ) in Nepalese secondary school. MATERIALS AND METHODS: Secondary school
students (n = 259, male = 43.63%, female = 56.37%) and local experts (n = 9, male
= 90%, female = 10%) were participated in this study. Evaluation processes were;
content validity (>0.89), plausibility check (>95), item-total correlation
(>0.3), factor loading (>0.4), principal component analysis (4 factors Kaiser's
criterion), Chronbach's alpha (>0.65), face validity and internal consistency
using test-retest reliability (P > 0.05). RESULTS: The principal component
analysis revealed four factors to be extracted; sexual health norms and beliefs,
source of sexual health information, sexual health knowledge and understanding,
and level of sexual awareness. Kaiser-Meyer-Olkin (KMO) measure of sampling
adequacy demonstrated that the patterns of correlations are relatively compact
(>0.80). Chronbach's alpha for each factors were above the cut-off point (0.65).
Face validity indicated that the questions were clear to the majority of the
respondent. Moreover, there were no significant differences (P > 0.05) in the
responses to the items at two time points at seven weeks later. CONCLUSIONS: The
finding suggests that SHQ is a valid and reliable instrument to be used in
schools to measure sexual health knowledge and understanding. Further analysis
such as structured equation modelling (SEM) and confirmatory factor analysis
could make the questionnaire more robust and applicable to the wider school
population.
PMID- 27500172
TI - Parental needs in infant's end-of-life and bereavement in NICU: A qualitative
study.
AB - BACKGROUND AND AIMS: Newborn death is an unexpected outcome for parents. Parents
face with several needs in infant end-of-life. The health care team is
responsible for meet these needs. This qualitative study aim was to explore of
parental needs in infant end-of-life and bereavement. MATERIALS AND METHODS: For
this qualitative study, 24 single semi-structure interviews were done. A
qualitative content analysis method was used. Sampling conducted on purposeful
with maximum variation in five Neonatal Intensive Care Unit (NICU) environments
in Isfahan city. Inclusion criteria for nurses and doctors were having at least
one experience of caring for an infant and their family at end-of-life. Inclusion
criteria for parents and their families were having at least one infant at end-of
life or had lost their infant for 6 months before in NICU. RESULTS: Data analysis
uncovered two main themes. Family's support needs with two subthemes (family's
support needs before infant's death and family's support needs after infant's
death) and family's preparatory needs upon infant's death with two subthemes
(management of the bad news of infant's death by treatment team and management of
the bad news of infant's death by family). DISCUSSION: Mourning mother's need for
her husband's presence by her side, getting hospitalized in a separate room, and
management of infant's death news by father and family were among items rarely
pointed out in other studies. Exploration of these needs cab be helpful for the
health care team for providing care.
PMID- 27500173
TI - Implementing clinical governance in Isfahan hospitals: Barriers and solutions,
2014.
AB - INTRODUCTION: In the new approach, all health care providers have been obligated
to maintain and improve the quality and have been accountable for it. One of the
ways is the implementation of clinical governance (CG). More accurate
understanding of its challenges can help to improve its performance. AIMS: In
this study, barriers of CG implementation are investigated from the perspective
of the hospitals involved. Besides, some solutions are suggested based on
stakeholders' opinions. MATERIALS AND METHODS: This study used combined method
(qualitative content analysis and questionnaire) in hospitals affiliated to
Isfahan University of Medical Sciences in 2014. First, experts, and stakeholders
talked about CG implementation obstacles in a semi-structured interview.
Interviews were confirmed by the interviewee (double check). After analyzing the
interviews using reduction coding the questionnaire was drawn up. The
questionnaire "validity was confirmed by Cronbach's alpha (0/891)" and its
reliability was obtained using experts confirmation. Data analyzing was performed
using SPSS (18) software. RESULTS: According to results staffing and management
factors were the main obstacles. After them, were factors related to
organizational culture, infrastructure elements, information, sociocultural and
then process factors. The learning barriers were in final rank. Thirty-four
solutions was proposed by experts and divided into subset of eight major
barriers. Most solutions were offered on modifying processes and minimal
solutions about modifying of organizational culture, sociocultural, and
educational factors. CONCLUSION: Removing the obstacles, especially management
and human resource factors can be effective by facilitating and accelerating CG.
Furthermore, use of experts and stakeholders opinions can help to remove CG
barriers.
PMID- 27500174
TI - The relationship between multi-dimensional self-compassion and fetal-maternal
attachment in prenatal period in referred women to Mashhad Health Center.
AB - BACKGROUND: Multi-dimensional self-compassion is one of the important factors
predicting fetal-maternal attachment which vary among different cultures and
countries. So the aim of this study was to determine the relationship between
multi-dimensional, self-compassion, and fetal-maternal attachment in the prenatal
period. SUBJECTS AND METHODS: This cross-sectional study was carried on 394
primigravida women to Mashhad Health Care Centers in with two stage sampling
method (cluster-convenience) in the year 2014. Demographic/prenatal
characteristics, multi-dimensional self-compassion (26Q) with five dimension
(including self-kindness, self-judgment, common humanity, isolation items,
mindfulness, over-identified), and fatal-maternal attachment (21Q) were completed
by the participants. The statistical analysis was performed with various
statistical tests such as Pearson correlation coefficient, t-test, one-way ANOVA,
and linear regression using SPSS statistical software (version 14). RESULTS:
Based on the findings, the mean (standard deviation) value for multi-dimensional
self-compassion was 59.81 (6.4) and for fatal-maternal attachment was 81.63
(9.5). There was a positive correlation between fatal-maternal attachment and
total self-compassion (P = 0.005, r = 0.30) and its dimension including self
kindness (P = 0.003, r = 0.24), self-judgment (P = 0.001, r = 0.18), common
humanity (P = 0.004, r = 0.28), isolation items (P = 0.006, r = 0.17),
mindfulness (P = 0.002, r = 0.15), over-identified (P = 0.001, r = 0.15).
CONCLUSIONS: There was a correlation between the multi-dimensional self
compassion and fetal-maternal attachment in pregnant women. Hence, educating
people like caregivers by community health midwives regarding psychological
problems in during pregnancy can be effective in early diagnosing and identifying
such disorders.
PMID- 27500175
TI - Comparison of the effect of web-based, simulation-based, and conventional
training on the accuracy of visual estimation of postpartum hemorrhage volume on
midwifery students: A randomized clinical trial.
AB - INTRODUCTION: Delay in diagnosis of bleeding can be due to underestimation of the
actual amount of blood loss during delivery. Therefore, this research aimed to
compare the efficacy of web-based, simulation-based, and conventional training on
the accuracy of visual estimation of postpartum hemorrhage volume. MATERIALS AND
METHODS: This three-group randomized clinical trial study was performed on 105
midwifery students in Mashhad School of Nursing and Midwifery in 2013. The
samples were selected by the convenience method and were randomly divided into
three groups of web-based, simulation-based, and conventional training. The three
groups participated before and 1 week after the training course in eight station
practical tests, then, the students of the web-based group were trained on-line
for 1 week, the students of the simulation-based group were trained in the
Clinical Skills Centre for 4 h, and the students of the conventional group were
trained for 4 h presentation by researchers. The data gathering tool was a
demographic questionnaire designed by the researchers and objective structured
clinical examination. Data were analyzed by software version 11.5. RESULTS: The
accuracy of visual estimation of postpartum hemorrhage volume after training
increased significantly in the three groups at all stations (1, 2, 4, 5, 6 and 7
(P = 0.001), 8 (P = 0.027)) except station 3 (blood loss of 20 cc, P = 0.095),
but the mean score of blood loss estimation after training did not significantly
different between the three groups (P = 0.95). CONCLUSION: Training increased the
accuracy of estimation of postpartum hemorrhage, but no significant difference
was found among the three training groups. We can use web-based training as a
substitute or supplement of training along with two other more common simulation
and conventional methods.
PMID- 27500176
TI - An investigation into the effect of health belief model-based education on
healthcare behaviors of nursing staff in controlling nosocomial infections.
AB - BACKGROUND: Health-care acquired infections are significant given the risks and
costs they impose. All previous studies indicate a poor level of knowledge and
performance among the nurses in hospital infections; as such, educating nurses
can play an important role in infection control. This study aimed at evaluating
the effects of the health belief model (HBM) in making nurses adopting health
care behaviors needed to control nosocomial infections (Nis). MATERIALS AND
METHODS: The participants of the study were 135 nurses from two hospitals in
Mashhad, Iran. A self-administered questionnaire was used to collect data. The
questionnaire consisted of seven parts. The intervention group received four 45
min educational programs, both in individual and collective forms. After a 2
month interval, a post-test was conducted to see whether any difference has been
resulted. RESULTS: There was a significant relationship between knowledge (P =
0.001), perceived threat (P = 0.004), perceived benefits (P = 0.001), and
practices (P = 0.001) in comparing to control and experimental groups after
intervention. For the experimental and control groups, the most frequent cues to
action at the preintervention stage were, respectively, related to the period of
studying at university and in-service classes. CONCLUSION: According to this
study, HBM-based education can increase knowledge, perceived threat, and
perceived benefits of nurses. Additionally, it can reduce perceived barriers and
improve the control of NIs among nurses.
PMID- 27500177
TI - Determinants of complementary feeding practices among mothers of 6-24 months
failure to thrive children based on behavioral analysis phase of PRECEDE model,
Tehran.
AB - BACKGROUND: This study intended to clarify the determining factors of
complementary feeding practices among Tehran 6-24 months failure to thrive
children in order to use the results for planning the interventions to reduce the
possible adverse effects. MATERIALS AND METHODS: In this study, 132 mothers of
three medical and health centers were chosen by random sampling among those
centers operating under the supervision of south of Tehran District Health Center
and study data were collected from them. A valid and reliable questionnaire as a
data collection instrument developed based on behavioral analysis phase of
PRECEDE model. Spearman and Pearson's correlation coefficient test were used to
determine the statistical relationship between factors associated with
complementary feeding practices among mothers. RESULTS: The mothers' knowledge
was as follows: 0.8%, 20.4%, and 78.8% of them were good, medium, and poor,
respectively. Mean scores for the mothers' performance in terms of supplementary
feeding was 66.8. Pearson correlation indicated a positive and significant
correlation between the mothers' performance with enabling and reinforcing
factors, but there wasn't any significant relationship between the mothers'
performance and knowledge about complementary feeding. CONCLUSIONS: According to
the obtained results, reinforcing factors, and enabling factors are associated
with the mothers' performance in terms of complementary feeding. Hence, attention
to these issues is essential for better health interventions planning.
PMID- 27500178
TI - Investigating the functionality of an OCT4-short response element in human
induced pluripotent stem cells.
AB - Pluripotent stem cells offer great therapeutic promise for personalized treatment
platforms for numerous injuries, disorders, and diseases. Octamer-binding
transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency
and self-renewal of mammalian cells. With site-specific integration for gene
correction in cellular therapeutics, use of the OCT4 promoter may have advantages
when expressing a suicide gene if pluripotency remains. However, the human OCT4
promoter region is 4 kb in size, limiting the capacity of therapeutic genes and
other regulatory components for viral vectors, and decreasing the efficiency of
homologous recombination. The purpose of this investigation was to characterize
the functionality of a novel 967bp OCT4-short response element during
pluripotency and to examine the OCT4 titer-dependent response during
differentiation to human derivatives not expressing OCT4. Our findings
demonstrate that the OCT4-short response element is active in pluripotency and
this activity is in high correlation with transgene expression in vitro, and the
OCT4-short response element is inactivated when pluripotent cells differentiate.
These studies demonstrate that this shortened OCT4 regulatory element is
functional and may be useful as part of an optimized safety component in a site
specific gene transferring system that could be used as an efficient and
clinically applicable safety platform for gene transfer in cellular therapeutics.
PMID- 27500179
TI - Closing the Gender Gap: The Case for Gender-Specific Alcoholism Research.
AB - As the number of women who use alcohol increases, so does the number of women who
engage in alcohol abuse and develop alcohol dependence. The recent increased
focus on women and gender differences in alcoholism research has largely come
about following recognition that the face of alcoholism is changing, with
alcoholism rates among men remaining stable and rising among women, particularly
in younger women. As such, the need to understand gender differences in both
acute and long-term effects of alcohol abuse has never been more critical. Gender
differences in the long-term effects of chronic alcoholism on the brain and other
systems are currently under debate, often with a focus on proclaiming whether men
or women suffer the most impact. However, the story appears to be more complex
than that. The issue of how alcoholism interacts with gender is complicated, as
gender differences in many factors including alcohol metabolism, alcoholism
progression, problematic drinking patterns, neurobiology, hormones, and
psychiatric comorbidities will contribute to the differences in structural and
functional outcomes observed experimentally across domains of inquiry. While
women are now much more commonly included in studies of alcohol's effects on the
brain, there remains a need for more explicit examinations of gender effects.
PMID- 27500180
TI - Respiratory Cancer and Non-Malignant Respiratory Disease-Related Mortality among
Older Construction Workers-Findings from the Health and Retirement Study.
AB - OBJECTIVE: This study explored the risk of respiratory cancer and non-malignant
respiratory disease (NMRD)-related mortality among older construction workers.
METHODS: Analyzed data from the 1992-2010 RAND Health and Retirement Study (HRS)
and the HRS National Death Index - Cause of Death file. About 25,183 workers aged
50 years and older were examined, including 5,447 decedents and 19,736 survivors,
of which 1,460 reported their longest job was in construction. Multinomial
logistic regression assessed the differences in mortality between workers'
longest occupations, controlling for confounders. RESULTS: After adjusting for
smoking and demographics, construction workers were almost twice as likely to die
from respiratory cancer (OR = 1.65; CI: 1.10-2.47) or NMRD (OR = 1.73; CI: 1.16
2.58) compared to white-collar workers. CONCLUSIONS: This study adds to the
growing evidence that respiratory cancer and NMRD are frequently associated with
construction exposure.
PMID- 27500181
TI - Amyloid-Beta Positron Emission Tomography Imaging of Alzheimer's Pathology in
Parkinson's Disease Dementia.
AB - BACKGROUND: Neuronal loss and alpha-synuclein (alpha-syn) pathology are
diagnostic of PD in the appropriate clinical context. However, some PD patients
have co-morbid Alzheimer's disease (AD) pathology on autopsy, including amyloid
beta (Abeta) plaques and neurofibrillary tangles. Florbetapir(18F) is a PET
ligand that detects Abeta pathology. We hypothesized that florbetapir(18F)
imaging could detect Abeta pathology in Parkinson disease dementia (PDD) patients
prior to death. OBJECTIVE: To determine the utility of florbetapir(18F) PET
imaging in detecting Abeta pathology in patients with autopsy-confirmed PDD.
METHODS: Five participants with PDD had florbetapir(18F) PET imaging prior to
death as a part of a longitudinal research study of cognitive decline in PD. PET
scans were evaluated by expert raters blinded to clinical and neuropathological
information. At autopsy, all five participants underwent semi-quantitative
assessments of regional Abeta and tau immunohistochemistry. RESULTS: All
participants met neuropathological criteria for PD. Two had both positive
florbetapir(18F) scans and Abeta-positive plaques in multiple brain regions.
Regional florbetapir(18F) binding correlated with regional semi-quantitative
Abeta pathology in these cases. Three cases had negative florbetapir(18F) scans.
Two of these had significant tau pathology without Abeta pathology, consistent
with progressive supranuclear palsy (PSP) in one case and argyrophilic grain
disease (AGD) in the other. The last case had a low level of AD neuropathological
change. CONCLUSIONS: Florbetapir(18F) Abeta imaging can detect the presence of
Abeta neuropathology in patients with PDD. This imaging technique may aid the
clinical evaluation of PDD patients to determine if cognitive decline is
occurring in the setting of Abeta accumulation.
PMID- 27500182
TI - Altered T-UCRs expression profile in the spinal cord of mice with neuropathic
pain.
AB - Spinal cord plays an important role in the transmission and modulation of
nociceptive information. Global changes in gene expression in the spinal cord
contribute to the induction and maintenance of neuropathic pain. Transcribed
Ultraconserved Regions (T-UCRs), a novel class of long noncoding RNAs, can
regulate gene expression at both transcriptional and post-transcriptional levels
and are related to many human diseases such as cancer, Alzheimer's disease, and
heart diseases. In this study, we screened abnormal T-UCRs expression in the
spinal cord under spinal nerve ligation (SNL)-induced neuropathic pain condition.
Microarray data showed the alternation of T-UCRs at the transcriptional level in
the spinal cord 10 days after SNL. Among 78 altered T-UCRs, 23 T-UCRs were
upregulated by more than 1.5-fold and 55 ones downregulated by less than 0.5-fold
after SNL. Hierarchical cluster analysis of T-UCRs expression profiles showed the
opposite expression pattern between SNL and sham-operated mice. The quantitative
real-time reverse transcription polymerase chain reaction analysis further
confirmed the expression patterns of uc.305, uc.189, uc.46, and uc.217 after SNL.
The gene ontology annotation and signaling pathway analysis for the T-UCRs host
genes indicated that differentially expressed T-UCRs were involved in several
intracellular activities and signaling pathways, including Ephrin receptor
activity, soluble NSF attachment protein receptor (SNARE) interactions in
vesicular transport pathway, and WNT signaling pathway. Collectively, the current
data suggest the possible role of T-UCR in the pathogenesis of neuropathic pain.
T-UCRs may serve as a new kind of target for the treatment of neuropathic pain.
PMID- 27500184
TI - In vitro Tumorsphere Formation Assays.
AB - A tumorsphere is a solid, spherical formation developed from the proliferation of
one cancer stem/progenitor cell. These tumorspheres (Figure 1a) are easily
distinguishable from single or aggregated cells (Figure 1b) as the cells appear
to become fused together and individual cells cannot be identified. Cells are
grown in serum-free, non-adherent conditions in order to enrich the cancer
stem/progenitor cell population as only cancer stem/progenitor cells can survive
and proliferate in this environment. This assay can be used to estimate the
percentage of cancer stem/progenitor cells present in a population of tumor
cells. The size, which can vary from less than 50 micrometers to 250 micrometers,
and number of tumorspheres formed can be used to characterize the cancer
stem/progenitor cell population within a population of in vitro cultured cancer
cells and within in vivo tumors (Lo et al., 2012; Liu et al., 2009). While
several cell lines can be used for tumorsphere formation assay (e.g. primary
mammary tumor cells from Her2/neu-transgenic mice, MCF7, BT474 and HCC1954), some
cell lines may not form typical tumorsphere structures and may be difficult to
count or classify definitively as tumorspheres.
PMID- 27500185
TI - Isolation of Cancer Epithelial Cells from Mouse Mammary Tumors.
AB - The isolation of cancer epithelial cells from mouse mammary tumor is accomplished
by digestion of the solid tumor. Red blood cells and other contaminates are
removed using several washing techniques such that primary epithelial cells can
further enriched. This procedure yields primary tumor cells that can be used for
in vitro tissue culture, fluorescence-activated cell sorting (FACS) and a wide
variety of other experiments (Lo et al., 2012).
PMID- 27500183
TI - The CRISPR/Cas9 system for gene editing and its potential application in pain
research.
AB - The CRISPR/Cas9 system is a research hotspot in genome editing and regulation.
Currently, it is used in genomic silencing and knock-in experiments as well as
transcriptional activation and repression. This versatile system consists of two
components: a guide RNA (gRNA) and a Cas9 nuclease. Recognition of a genomic DNA
target is mediated through base pairing with a 20-base gRNA. The latter further
recruits the Cas9 endonuclease protein to the target site and creates double
stranded breaks in the target DNA. Compared with traditional genome editing
directed by DNA-binding protein domains, this short RNA-directed Cas9
endonuclease system is simple and easily programmable. Although this system may
have off-target effects and in vivo delivery and immune challenges, researchers
have employed this system in vivo to establish disease models, study specific
gene functions under certain disease conditions, and correct genomic information
for disease treatment. In regards to pain research, the CRISPR/Cas9 system may
act as a novel tool in gene correction therapy for pain-associated hereditary
diseases and may be a new approach for RNA-guided transcriptional activation or
repression of pain-related genes. In addition, this system is also applied to
loss-of-function mutations in pain-related genes and knockin of reporter genes or
loxP tags at pain-related genomic loci. The CRISPR/Cas9 system will likely be
carried out widely in both bench work and clinical settings in the pain field.
PMID- 27500186
TI - In vitro Assay for Cytidine Deaminase Activity of APOBEC3 Protein.
AB - Cytidine deaminases are enzymes that catalyze the removal of an amino group from
cytidine, forming uridine. APOBEC3 (ApolipoproteinB mRNA editing enzyme,
catalytic polypeptide like) proteins are cytidine deaminases that deaminate
cytidines in polynucleotides (RNA/DNA), resulting in editing of their target
substrates. Mammalian APOBEC3 proteins are an important element in cellular
defenses against retrovirus replication, and this "restriction" of retroviral
infections is partially due to the cytidine deaminase activity of the APOBEC3.
The present protocol (Nair et al., 2014) describes the assay to detect the
deaminase activity of mouse APOBEC3 protein, which targets cytidines present in
TCC or TTC motifs in a single-stranded DNA substrate. In brief, the protein
preparation to be assayed is incubated with a fluorophore-labeled
oligodeoxynucleotide containing the deamination target motif (radiolabeled
oligonucleotide substrates have also been successfully used by other groups).
Cytidines in the oligonucleotide are deaminated to uridines; the addition of
Uracil DNA Glycosylase (UDG) catalyzes the hydrolysis of the N-glycosylic bond
between uracil and sugar, generating an abasic (AB) site in the oligonucleotide.
Mild alkali treatment cleaves the substrate oligonucleotide at the AB site;
cleaved products are resolved from uncleaved substrate by denaturing
polyacrylamide gel electrophoresis and visualized on a fluorescence scanner. The
protocol described here is mainly adapted from that described by Iwatani et al.
(2006) with modifications. The assay can, of course, be used to detect the
activity of other APOBEC3 deaminases targeting DNA substrates, using
oligonucleotides containing the cytidine-containing target sequence for the
deaminase.
PMID- 27500187
TI - Primer Extension Reactions for the PCR- based alpha- complementation Assay.
AB - The PCR- based- alpha- complementation assay is an effective technique to measure
the fidelity of polymerases, especially RNA-dependent RNA polymerases (RDRP) and
Reverse Transcriptases (RT). It has been successfully employed to determine the
fidelity of the poliovirus polymerase 3D-pol (DeStefano, 2010) as well as the
human immunodeficiency virus Reverse Transcriptase (HIV RT) (Achuthan et al.,
2014). A major advantage of the assay is that since the PCR step is involved,
even the low yield of products obtained after two rounds of low yield of RNA
synthesis (for RDRP) or reverse transcription (for RT) can be measured using the
assay. The assay also mimics the reverse transcription process, since both RNA-
and DNA- directed RT synthesis steps are performed. We recently used this assay
to show that the HIV RT, at physiologically relevant magnesium concentration, has
accuracy in the same range as other reverse transcriptases (Achuthan et al.,
2014). Here, we describe in detail how to prepare the inserts using the primer
extension reactions. The prepared inserts are then processed further in the PCR-
based- alpha- complementation assay.
PMID- 27500188
TI - Telomere Dysfunction Induced Foci (TIF) Analysis.
AB - Telomerase maintains telomeric DNA in eukaryotes during early developments, ~90%
of cancer cells and some proliferative stem like cells. Telomeric repeats at the
end of chromosomes are associated with the shelterin complex. This complex
consists of TRF1, TRF2, Rap1, TIN2, TPP1, POT1 which protect DNA from being
recognized as DNA double-stranded breaks. Critically short telomeres or impaired
shelterin proteins can cause telomere dysfunction, which eventually induces DNA
damage responses at the telomeres. DNA damage responses can be identified by
antibodies to 53BP1, gammaH2AX, Rad17, ATM, and Mre11. DNA damage foci at
uncapped telomeres are referred to as Telomere dysfunction-Induced Foci (TIFs)
(de Lange, 2005; Takai et al., 2003). The TIF assay is based on the co
localization detection of DNA damage by an antibody against DNA damage markers,
such as gamma-H2AX, and telomeres using an antibody against one of the shelterin
proteins such as TRF2 (Takai et al., 2003; de Lange, 2002; Karlseder et al.,
1999). The method we describe here can be used in normal human and cancer cells.
Other commonly used methods-Telomere Restriction Fragment (TRF) Analysis (Mender
and Shay, 2015b) and Telomere Repeat Amplification Protocol (TRAP) (Mender and
Shay, 2015a)- in telomere biology can be found by clicking on the indicated
links.
PMID- 27500189
TI - Telomere Restriction Fragment (TRF) Analysis.
AB - While telomerase is expressed in ~90% of primary human tumors, most somatic
tissue cells except transiently proliferating stem-like cells do not have
detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001).
Telomeres progressively shorten with each cell division in normal cells,
including proliferating stem-like cells, due to the end replication (lagging
strand synthesis) problem and other causes such as oxidative damage, therefore
all somatic cells have limited cell proliferation capacity (Hayflick limit)
(Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere
shortening eventually leads to growth arrest in normal cells, which is known as
replicative senescence (Shay et al., 1991). Once telomerase is activated in
cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to
the end of chromosomes, thus enabling the limitless continuation of cell division
(Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging
and cancer can be partially explained by telomere biology. There are many rapid
and convenient methods to study telomere biology such as Telomere Restriction
Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay,
2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay,
2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF)
analysis to determine average telomeric length of cells. Telomeric length can be
indirectly measured by a technique called Telomere Restriction Fragment analysis
(TRF). This technique is a modified Southern blot, which measures the
heterogeneous range of telomere lengths in a cell population using the length
distribution of the terminal restriction fragments (Harley et al., 1990;
Ouellette et al., 2000). This method can be used in eukaryotic cells. The
description below focuses on the measurement of human cancer cells telomere
length. The principle of this method relies on the lack of restriction enzyme
recognition sites within TTAGGG tandem telomeric repeats, therefore digestion of
genomic DNA, not telomeric DNA, with a combination of 6 base restriction
endonucleases reduces genomic DNA size to less than 800 bp.
PMID- 27500190
TI - Data on greenhouse gases emission in condensate separation unit of a
petrochemical company in Iran.
AB - Since global warming due to greenhouse gas emissions is no respecter of
geographical boundaries of countries, concerted mitigation activities such as
Clean Development Mechanism (CDM), are suitable. In this mechanism, some
developed countries can gain certified emission reduction credits from emission
reduction actions undertaken in developing countries. Thus, the data of
greenhouse gas emissions in developing countries would be informative for
implementing of CDM. Herein, the data of greenhouse gas emissions of Bandar Imam
Petrochemical Complex, one of the biggest petrochemical companies in the Middle
East region is presented. The data was acquired using emission factor method and
self-presented raw information of the Bandar Imam Petrochemical Complex. Overall,
the data will be interesting for environmentalists, non-governmental organization
(NGO), and developed countries to perform CDM.
PMID- 27500191
TI - Processed data for CHMS 2007-2009: Bisphenol A, phthalates and lead and learning
and behavioral problems in Canadian children 6-19 years of age.
AB - This article presents processed data from an analysis of cross-sectional data
from Cycle 1 of the Canadian Health Measures Survey (CHMS) to examine the
potential association between urinary concentrations of BPA and phthalate
metabolites and child learning and behavioral problems, considering important
covariates such as gender, blood lead and environmental tobacco smoke (ETS).
These processed data are related to the research on a subset of the children
(Arbuckle et al., 2016) [1]. The Strengths and Difficulties Questionnaire (SDQ)
outcomes of interest were emotional symptoms, hyperactivity/inattention, and a
total difficulties SDQ score, with borderline and abnormal scores grouped
together and compared with children with normal scores. Other outcomes studied
included reported learning disability, ADD/ADHD (attention deficit
disorder/attention deficit hyperactivity disorder) and use of psychotropic
medications to treat behavioral disorders in the past month. Data are presented
for all children 6-19 years of age combined. Weighted simple logistic regression
estimates for important covariates of each of the outcomes from CHMS Cycle 1
children are reported. Odds ratios based on weighted multiple logistic regression
estimates for urinary BPA and phthalate metabolites (including specific gravity
as a covariate) and blood lead are presented for the reported outcomes ADD/ADHD,
learning disability and psychotropic medications, as well as the SDQ outcomes
emotional symptoms, hyperactivity/inattention and total difficulties.
PMID- 27500192
TI - Standardized norm data for three self-report scales on egocentric and allocentric
environmental spatial strategies.
AB - Standardized norm data for three scales of a 19-item self-report measure on
environmental spatial strategies are provided. This self-report measure comprises
egocentric spatial strategies, an allocentric mental map strategy and knowledge
of cardinal directions as three separate scales, "Validation of a 3-factor
structure of spatial strategies and relations to possession and usage of
navigational aids" (Munzer et al., 2016) [3]. The data are based on a large
sample (N>4000) representative for the population in Germany. Standardized norm
data for men and women in different age groups are provided through percentile
ranks and T-values.
PMID- 27500193
TI - Data on importance of hematopoietic cell derived Lipocalin 2 against gut
inflammation.
AB - The data herein is related to the research article entitled "Microbiota-inducible
innate immune siderophore binding protein Lipocalin 2 is critical for intestinal
homeostasis" (Singh et al., 2016) [1]. In the present article, we monitored
dextran sodium sulfate (DSS)-induced colitis development upon Lipocalin 2 (Lcn2)
neutralization, and examined the survival of Lcn2 deficient (Lcn2KO) mice and
their WT littermates upon DSS challenge. To dissect the relative contribution of
immune and non-immune cells-derived Lcn2 in mediating protection against gut
inflammation, we generated respective bone marrow chimera and evaluated their
susceptibility to IL-10 receptor neutralization-induced chronic colitis.
Neutralization of Lcn2 in WT mice resulted in exacerbated DSS-induced colitis.
Notably, mice lacking Lcn2 exhibited 100% mortality whereas only 20% mortality
was observed in WT mice upon DSS challenge. Further, data from bone marrow
chimera showed that immune cell-derived Lcn2 is the major contributor in
conferring protection against colitis.
PMID- 27500194
TI - Dataset exploited for the development and validation of automated cyanobacteria
quantification algorithm, ACQUA.
AB - The estimation and quantification of potentially toxic cyanobacteria in lakes and
reservoirs are often used as a proxy of risk for water intended for human
consumption and recreational activities. Here, we present data sets collected
from three volcanic Italian lakes (Albano, Vico, Nemi) that present filamentous
cyanobacteria strains at different environments. Presented data sets were used to
estimate abundance and morphometric characteristics of potentially toxic
cyanobacteria comparing manual Vs. automated estimation performed by ACQUA
("ACQUA: Automated Cyanobacterial Quantification Algorithm for toxic filamentous
genera using spline curves, pattern recognition and machine learning" (Gandola et
al., 2016) [1]). This strategy was used to assess the algorithm performance and
to set up the denoising algorithm. Abundance and total length estimations were
used for software development, to this aim we evaluated the efficiency of
statistical tools and mathematical algorithms, here described. The image
convolution with the Sobel filter has been chosen to denoise input images from
background signals, then spline curves and least square method were used to
parameterize detected filaments and to recombine crossing and interrupted
sections aimed at performing precise abundances estimations and morphometric
measurements.
PMID- 27500195
TI - Characterisation data of simple sequence repeats of phages closely related to
T7M.
AB - Coliphages T7M and T3, Yersinia phage phiYeO3-12, and Salmonella phage phiSG-JL2
share high homology in genomic sequences. Simple sequence repeats (SSRs) are
found in their genomes and variations of SSRs among these phages are observed.
Analyses on regions of sequences in T7M and T3 genomes that are likely derived
from phage recombination, as well as the counterparts in phiYeO3-12 and phiSG
JL2, have been discussed by Lin in "Simple sequence repeat variations expedite
phage divergence: mechanisms of indels and gene mutations" [1]. These regions are
referred to as recombinant regions. The focus here is on SSRs in the whole genome
and regions of sequences outside the recombinant regions, referred to as non
recombinant regions. This article provides SSR counts, relative abundance,
relative density, and GC contents in the complete genome and non-recombinant
regions of these phages. SSR period sizes and motifs in the non-recombinant
regions of phage genomes are plotted. Genomic sequence changes between T7M and T3
due to insertions, deletions, and substitutions are also illustrated. SSRs and
nearby sequences of T7M in the non-recombinant regions are compared to the
sequences of phiYeO3-12 and phiSG-JL2 in the corresponding positions. The
sequence variations of SSRs due to vertical evolution are classified into four
categories and tabulated: (1) insertion/deletion of SSR units, (2)
expansion/contraction of SSRs without alteration of genome length, (3) changes of
repeat motifs, and (4) generation/loss of repeats.
PMID- 27500196
TI - The Future of Intravesical Drug Delivery for Non-Muscle Invasive Bladder Cancer.
AB - Despite being the fifth most common cancer in the United States, minimal progress
has been made in the treatment of bladder cancer in over a decade. Intravesical
instillation of Bacillus Calmette-Guerin (BCG) for the treatment of non-muscle
invasive bladder cancer (NMIBC) has been in use for over 30 years and remains the
standard treatment in cases of intermediate and high risk disease. Despite the
relative success of intravesical BCG, unmet needs in the treatment of NMIBC
persist. These challenges include disease recurrence and progression even with
treatment with BCG, as well as issues regarding its availability and patient
tolerability. The inherent properties of the bladder pose the biggest obstacle to
developing effective intravesical treatments for NMIBC. Current research is now
focusing on methods to improve the delivery of intravesical therapies. The
objective of this review is to discuss novel intravesical drug delivery systems
and how they are addressing these challenges in the treatment of NMIBC.
PMID- 27500197
TI - Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus
White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non
Muscle Invasive Bladder Cancer.
AB - Introduction: Although there is evidence that hexaminolevulinate (HAL)-based
transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non
muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is
uncertainty about its beneficial effects on progression. Material and Methods: A
systematic literature search was conducted according to the PRISMA statement to
identify studies reporting on HAL- vs. white-light (WL-) based TUR-BT in non
muscle invasive bladder cancer between 2000 and 2016. A two-stage selection
process was utilized to determine eligible studies. Of a total of 294 studies, 5
(4 randomized and one retrospective) were considered for final analysis. The
primary objective was the rate of progression. Results: The median follow-up for
patients treated with HAL- and WL-TURBT was 27.6 (1-55.1) and 28.9 (1-53) months,
respectively. Of a total of 1301 patients, 644 underwent HAL- and 657 WL-based
TURBT. Progression was reported in 44 of 644 patients (6.8%) with HAL- and 70 of
657 patients (10.7%) with WL-TURBT, respectively (median odds ratio: 1.64, 1.10
2.45 for HAL vs. WL; p = 0.01). Data on progression-free survival was reported in
a single study with a trend towards improved survival for patients treated with
HAL-TURBT (p = 0.05). Conclusions: In this meta-analysis the rate of progression
was significantly lower in patients treated with HAL- vs. WL-based TURBT. These
results support the initiation of randomized trials on HAL with progression as
primary endpoint.
PMID- 27500199
TI - The Relationship between Centralization of Care and Geographic Barriers to
Cystectomy for Bladder Cancer.
AB - Background: Centralization of cystectomy treatment for bladder cancer, while
associated with improved outcomes, may impose geographic barriers to care.
However, whether this effect may be counterbalanced by an increased number of
high volume centers has not previously been explored. Objective: To characterize
changes in geographic disparities to high volume cystectomy centers over time.
Methods: Data on all inpatient admissions for cystectomy in New York State (NYS)
from 1997-2011 was obtained from the Department of Health. Using these data, we
classified hospitals according to cystectomy volume and measured patient distance
traveled to a cystectomy center. Population weights, from the US Census, were
used to describe changes in minimum travel distance to high- or very high-volume
(HV/VHV) facilities across the NYS population. Results: Bladder cancer patients
underwent cystectomies at 195 hospitals during the study period. In 1997-2001,
eleven HV/VHV facilities accounted for 37.5% of all cystectomies, while sixteen
HV/VHV hospitals accounted for 71.5% of all procedures during 2007-2011. Median
distance traveled by cystectomy patients to all hospitals increased from 9.6 to
14.4 miles in 1997-2001 to 2007-2011, respectively. In the same time span, the
median travel distance for the NYS population to a HV/VHV center decreased by 1.9
and 9.4 miles at the median and 75th percentile, respectively. Conclusions: Our
findings demonstrate a complicated relationship between centralization and
geographic access. While centralization has led to a decrease in overall access
to cystectomy facilities, the process simultaneously improved access to high
volume centers.
PMID- 27500200
TI - Assessing Symptom Burden in Bladder Cancer: An Overview of Bladder Cancer
Specific Health-Related Quality of Life Instruments.
AB - Background: A key component to monitoring and investigating patient QOL is
through patient reported health related quality of life (HRQOL) outcome measures.
Many instruments have been used to assess HRQOL in bladder cancer and each
instrument varies in its development, validation, the context of its usage in the
literature and its applicability to certain disease states. Objective: In this
review, we sought to summarize how clinicians and researchers should most
appropriately utilize the available HRQOL instruments for bladder cancer.
Methods: We performed a comprehensive literature search of each instrument used
in bladder cancer, paying particular attention to the outcomes assessed. We used
these outcomes to group the available instruments into categories best reflecting
their optimal usage by stage of disease. Results: We found 5 instruments specific
to bladder cancer, of which 3 are validated. Only one of the instruments (the
EORTC-QLQ-NMIBC24) was involved in a randomized, prospective validation study.
The most heavily used instruments are the EORTC-QLQ-BLM30 for muscle-invasive
disease and the FACT-Bl which is used across all disease states. Of the 5
available instruments, 4 are automatically administered with general instruments,
while the BCI lacks modularity, and requires co-administration with a generalized
instrument. Conclusion: There are multiple strong instruments for use in gauging
HRQOL in bladder cancer patients. We have divided these instruments into three
categories which optimize their usage: instruments for use following NMIBC
treatments (EORTC-QLQ-NMIBC24), instruments for use following radical cystectomy
(FACT-Bl-Cys and EORTC-QLQ-BLM30) and more inclusive instruments not limited by
treatment modality (BCI and FACT-Bl).
PMID- 27500201
TI - Obesity and Outcomes in Patients with Metastatic Urothelial Carcinoma.
AB - Background: Obesity has been associated with worse outcomes in patients with
clinically localized urothelial cancer. However, this impact has not been
evaluated in metastatic disease. Objective: To assess the impact of obesity on
outcomes of patients with metastatic urothelial cancer. Methods: Data from 537
patients were aggregated from eight phase II and phase III clinical trials
investigating first-line cisplatin-based combination therapy in metastatic
urothelial cancer. Chemotherapy regimen, adverse events, treatment response, and
survival outcomes were compared across body mass index (BMI) and body surface
area (BSA) categories. Results: BMI was classified according to WHO criteria
(<18.5 underweight, 18.5-24.99 normal weight, 25-29.99 overweight, >30 obese).
BSA was classified as either below or greater than or equal to (average for this
cohort (1.87 m2 for males and 1.66 m2 for females). There was no significant
difference in number of chemotherapy cycles, adverse events, and response rate or
survival outcomes (overall and progression-free) across BMI and BSA categories.
There was no significant difference in adverse events across BMI categories, but
the incidences of embolic events and renal failure were higher in patients with
an average or higher BSA than those with a lower than average BSA (6.6% vs. 3.1%
for renal failure p = 0.06; 5.9% vs. 2.7% for renal failure, p = 0.07). There was
no significant difference in response rate or survival outcomes (overall and
progression-free) amongst BMI and BSA categories. Conclusions: Obese patients
with metastatic urothelial cancer on cisplatin-based therapies have similar
response rates, survival outcomes, and tolerability of cisplatin-based therapy to
non-obese patients.
PMID- 27500202
TI - Elevated Derived Neutrophil-to-Lymphocyte Ratio Corresponds With Poor Outcome in
Patients Undergoing Pre-Operative Chemotherapy in Muscle-Invasive Bladder Cancer.
AB - Background: Platinum-based pre-operative chemotherapy (POC) for muscle-invasive
bladder cancer (MIBC) increases the complete pathological response rate at
cystectomy and improves overall survival. However, 60% of MIBC patients still has
muscle-invasive disease at cystectomy despite POC. Therefore, accurate prediction
of response to POC is an important clinical need. We hypothesized that an
elevated neutrophil-to-lymphocyte ratio (NLR) corresponds with adverse outcome in
patients undergoing POC and radical cystectomy. Objective: To explore the
correlation between the NLR and outcome in MIBC patients treated by POC and
radical cystectomy. Methods: In 123 MIBC patients (urothelial carcinoma) who were
treated by platinum-based POC and radical cystectomy, the derived NLR (dNLR) was
retrospectively calculated by dividing the neutrophil count by the difference
between leukocytes and neutrophil counts, prior to the start of chemotherapy. The
correlation of the dNLR with pathological response at cystectomy and survival was
analyzed by logistic regression analysis or the Kaplan-Meier method. Results: The
complete pathological response (ypT0N0Mx) rate was 28.5%, 8.9% obtained a partial
response (ypTa/T1/TisN0Mx), and 62.6% were non-responders (stage >= ypT2 and/or
N+). An elevated dNLR (>2.21) correlated with non-response to POC (OR 2.70, 95%
confidence interval: 1.15-6.38, p = 0.02) but this effect was nullified when
corrected for clinically node-positive disease and clinical T stage. Patients
with an elevated dNLR had shorter progression-free and overall survival albeit
non-significant (p = 0.42, and p = 0.45, respectively). Conclusions: An elevated
dNLR corresponded with poor outcome in terms of survival and non-response to POC
in MIBC patients undergoing radical surgery. However, after correction for well
known prognostic factors, such as positive lymph node status at diagnostic
imaging and clinical T stage, the correlation for the dNLR was nullified.
Therefore, we conclude that the dNLR is insufficient to predict response to POC
in this heterogeneous patient population.
PMID- 27500203
TI - Clinical Trials Corner.
PMID- 27500198
TI - A Systematic Review of the Diagnostic and Prognostic Value of Urinary Protein
Biomarkers in Urothelial Bladder Cancer.
AB - For over 80 years, cystoscopy has remained the gold-standard for detecting
tumours of the urinary bladder. Since bladder tumours have a tendency to recur
and progress, many patients are subjected to repeated cystoscopies during long
term surveillance, with the procedure being both unpleasant for the patient and
expensive for healthcare providers. The identification and validation of bladder
tumour specific molecular markers in urine could enable tumour detection and
reduce reliance on cystoscopy, and numerous classes of biomarkers have been
studied. Proteins represent the most intensively studied class of biomolecule in
this setting. As an aid to researchers searching for better urinary biomarkers,
we report a comprehensive systematic review of the literature and a searchable
database of proteins that have been investigated to date. Our objective was to
classify these proteins as: 1) those with robustly characterised sensitivity and
specificity for bladder cancer detection; 2) those that show potential but
further investigation is required; 3) those unlikely to warrant further
investigation; and 4) those investigated as prognostic markers. This work should
help to prioritise certain biomarkers for rigorous validation, whilst preventing
wasted effort on proteins that have shown no association whatsoever with the
disease, or only modest biomarker performance despite large-scale efforts at
validation.
PMID- 27500204
TI - Beyond Cisplatin - I.
PMID- 27500206
TI - NMR Signal Amplification by Reversible Exchange of Sulfur-Heterocyclic Compounds
Found In Petroleum.
AB - NMR hyperpolarization via Signal Amplification by Reversible Exchange (SABRE) was
employed to investigate the feasibility of enhancing the NMR detection
sensitivity of sulfur-heterocycles (specifically 2-methylthiophene and
dibenzothiophenes), a family of compounds typically found in petroleum and
refined petroleum products. SABRE hyperpolarization of sulfur-heterocycles
(conducted in seconds) offers potential advantages of providing structural
information about sulfur-containing contaminants in petroleum, thereby informing
petroleum purification and refining to minimize sulfur content in refined
products such as gasoline. Moreover, NMR spectroscopy sensitivity gains endowed
by hyperpolarization potentially allows for performing structural assays using
inexpensive, low-magnetic-field (ca. 1 T) high-resolution NMR spectrometers
ideally suited for industrial applications in the field.
PMID- 27500205
TI - Of Kindlins and Cancer.
AB - Kindlins are 4.1-ezrin-ridixin-moesin (FERM) domain containing proteins. There
are three kindlins in mammals, which share high sequence identity. Kindlin-1 is
expressed primarily in epithelial cells, kindlin-2 is widely distributed and is
particularly abundant in adherent cells, and kindlin-3 is expressed primarily in
hematopoietic cells. These distributions are not exclusive; some cells express
multiple kindlins, and transformed cells often exhibit aberrant expression, both
in the isoforms and the levels of kindlins. Great interest in the kindlins has
emerged from the recognition that they play major roles in controlling integrin
function. In vitro studies, in vivo studies of mice deficient in kindlins, and
studies of patients with genetic deficiencies of kindlins have clearly
established that they regulate the capacity of integrins to mediate their
functions. Kindlins are adaptor proteins; their function emanate from their
interaction with binding partners, including the cytoplasmic tails of integrins
and components of the actin cytoskeleton. The purpose of this review is to
provide a brief overview of kindlin structure and function, a consideration of
their binding partners, and then to focus on the relationship of each kindlin
family member with cancer. In view of many correlations of kindlin expression
levels and neoplasia and the known association of integrins with tumor
progression and metastasis, we consider whether regulation of kindlins or their
function would be attractive targets for treatment of cancer.
PMID- 27500207
TI - An Open Letter to HHS Secretary Burwell on Ethically Increasing Organ Donation.
PMID- 27500208
TI - Postrenal Transplant Human T-Cell Lymphotropic Virus Type I-Associated
Myelopathy/Tropical Spastic Paraparesis: A Case Report and Review of the
Literature.
AB - We report a case of human T-cell lymphotropic virus type I (HTLV-I)-associated
myelopathy/tropical spastic paraparesis (HAM/TSP), in a 59 year-old, living
donor, renal transplant recipient from Jamaica. The patient's renal transplant
had been performed 11 years ago, and her organ donor was also from Jamaica.
Pretransplant HTLV-I serologic status for both the donor and recipient was
unknown. The prevalence of HTLV-I seropositivity in the United States and Europe
is low, and HAM/TSP is a rare occurrence. The positive predictive value of HTLV-I
screening in these regions is therefore, low. This has generated debate among
transplant societies regarding universal screening for HTLV-I before solid organ
transplantation. Very limited evidence is available for the prevention and
treatment of this devastating condition. Our case highlights the importance of
selected pretransplant screening for HTLV-I infection among organ donors and
candidates from endemic areas. We feel such testing may aid in the early
recognition of HAM/TSP and more timely initiation of treatment.
PMID- 27500209
TI - Detection of Virus-Specific CD8+ T Cells With Cross-Reactivity Against
Alloantigens: Potency and Flaws of Present Experimental Methods.
AB - Virus-specific T cells have the intrinsic capacity to cross-react against
allogeneic HLA antigens, a phenomenon known as heterologous immunity. In
transplantation, these cells may contribute to the alloimmune response and
negatively impact graft outcome. This study describes the various techniques that
can be used to detect heterologous immune responses of virus-specific CD8(+) T
cells against allogeneic HLA antigens. The strengths and weaknesses of the
different approaches are discussed and illustrated by experimental data. METHODS:
Mixed-lymphocyte reactions (MLRs) were performed to detect allo-HLA cross
reactivity of virus-specific CD8(+) T cells in total peripheral blood mononuclear
cells. T-cell lines and clones were generated to confirm allo-HLA cross
reactivity by IFNgamma production and cytotoxicity. In addition, the conventional
MLR protocol was adjusted by introducing a 3-day resting phase and subsequent
short restimulation with alloantigen or viral peptide, whereupon the expression
of IFNgamma, IL-2, CD107a, and CD137 was determined. RESULTS: The accuracy of
conventional MLR is challenged by potential bystander activation. T-cell lines
and clones can circumvent this issue, yet their generation is laborious and time
consuming. Using the adjusted MLR and restimulation protocol, we found that only
truly cross-reactive T cells responded to re-encounter of alloantigen and viral
peptide, whereas bystander-activated cells did not. CONCLUSIONS: The introduction
of a restimulation phase improved the accuracy of the MLR as a screening tool for
the detection of allo-HLA cross-reactivity by virus-specific CD8(+) T cells at
bulk level. For detailed characterization of cross-reactive cells, T-cell lines
and clones remain the golden standard.
PMID- 27500210
TI - Value of Magnetic Resonance Cholangiopancreatography in Assessment of
Nonanastomotic Biliary Strictures After Liver Transplantation.
AB - Nonanastomotic biliary strictures (NAS) remain a frequent complication after
orthotopic liver transplantation (OLT). The aim of this study was to evaluate
whether magnetic resonance cholangiopancreatography (MRCP) could be used to
detect NAS and to grade the severity of biliary strictures. METHODS: In total, 58
patients after OLT from 2 Dutch transplantation centers in whom endoscopic
retrograde cholangiopancreatography or percutaneous transhepatic cholangiography
and MRCP were performed within less than 6 months apart were included in the
study. Of these patients, 41 had NAS and 17 were without NAS based on endoscopic
retrograde cholangiopancreatography or percutaneous transhepatic cholangiography
and follow-up. Four radiologists-2 from each center-used an adapted validated
classification-termed "Leiden Biliary Stricture Classification" "(LBSC)-to
evaluate the MRCP examinations independently. In this classification, NAS
severity is assessed in 4 hepatobiliary regions. Interobserver agreement of the
severity score for each region was calculated with the kappa statistics. RESULTS:
Optimal cutoff value of the LBSC to detect the presence of NAS with MRCP was
calculated at 3 points or greater for all readers. Applying this cutoff
sensitivity for each reader was greater than 90%, with a specificity of 50% to
82%, positive predictive value of 86% to 91%, and negative predictive value of
80% to 100%. The MRCP performance was better in evaluation of the intrahepatic
than of the extrahepatic bile ducts. The additional value of MRCP for grading
severity of NAS was limited. CONCLUSIONS: The MRCP with the LBSC is a reliable
tool to detect or exclude NAS after OLT. Currently, MRCP cannot be used to
reliably grade the severity of these strictures.
PMID- 27500211
TI - The Cost and Utility of Renal Transplantation in Malaysia.
AB - Kidney transplantation is the optimal therapy for the majority of patients with
end-stage renal disease. However, the cost and health outcomes of transplantation
have not been assessed in a middle-income nation with a low volume of
transplantation, such as Malaysia. AIM AND METHODS: This study used microcosting
methods to determine the cost and health outcomes of living and deceased donor
kidney transplantation in adult and pediatric recipients. The perspective used
was from the Ministry of Health Malaysia. Cost-effectiveness measures were cost
per life year (LY) and cost per quality-adjusted LYs. The time horizon was the
lifetime of the transplant recipient from transplant to death. RESULTS: Records
of 206 KT recipients (118 adults and 88 children) were obtained for microcosting.
In adults, discounted cost per LY was US $8609(Malaysian Ringgit [RM]29 482) and
US $13 209(RM45 234) for living-donor kidney transplant (LKT) and deceased donor
kidney transplant (DKT), respectively, whereas in children, it was US $10
485(RM35 905) and US $14 985(RM51 317), respectively. Cost per quality-adjusted
LY in adults was US $8826 (RM30 224) for LKT and US $13 592(RM46 546) for DKT.
Total lifetime discounted costs of adult transplants were US $119 702 (RM409 921)
for LKT, US $147 152 (RM503 922) for DKT. Total costs for pediatric transplants
were US $154 841(RM530 252) and US $159 313(RM545 566) for the 2 categories
respectively. CONCLUSIONS: Both LKT and DKT are economically favorable for
Malaysian adult and pediatric patients with ESRD and result in improvement in
quality of life.
PMID- 27500212
TI - Pyloroplasty for Refractory Diabetic Gastroparesis After Renal Transplantation.
PMID- 27500213
TI - Cyclic Helix B Peptide in Preservation Solution and Autologous Blood Perfusate
Ameliorates Ischemia-Reperfusion Injury in Isolated Porcine Kidneys.
AB - There is a critical need to better preserve isolated organs before
transplantation. We developed a novel nonerythropoiesis cyclic helix B peptide
(CHBP) derived from erythropoietin, which has potent tissue protection and
prolonged serum stability. The renoprotection and potential mechanism of CHBP
were evaluated in a kidney preservation model. MATERIALS AND METHODS: Porcine
kidneys (n = 5) subjected to 20-minute warm ischemia were retrieved and flushed
with hyperosmolar citrate to mimic deceased donation. The kidneys and autologous
blood +/- 10.56 nmol/L CHBP were placed in cold storage (CS) for 18 hours. These
kidneys were then normothermically hemoreperfused for 3 hours using an isolated
organ perfusion system. The renal function and structure, apoptosis,
inflammation, and expression of caspase-3 and heat shock protein 70 (HSP70) were
assessed. RESULTS: Cyclic helix B peptide significantly increased the renal blood
flow, oxygen consumption, and urine output during reperfusion, but decreased
serum potassium and renal tissue damage. Apoptotic cells were significantly
decreased in the tubular areas, but increased in the lumens and interstitial
areas in the post-CS and postreperfused kidneys, whereas myeloperoxidase+ cells
were reduced. In addition, the expression of both caspase-3 precursor and active
subunits was downregulated by CHBP in reperfused kidneys. However, HSP70 was
upregulated in the post-CS and postreperfused kidneys treated with CHBP.
CONCLUSIONS: Cyclic helix B peptide administered into preservation and
reperfusion solutions ameliorated renal ischemia-reperfusion injury, which might
be associated with decreased apoptosis, inflammation and caspase-3, but increased
HSP70. This novel preservation approach using CHBP may be applied in a porcine
kidney transplant model and potential human donor kidney preservation.
PMID- 27500214
TI - A Safety and Efficacy Study of Medium-Dose Etoposide, Cyclophosphamide and Total
Body Irradiation Conditioning Before Allogeneic Stem Cell Transplantation for
Acute Lymphoblastic Leukemia.
AB - Prognosis for adult patients with acute lymphoblastic leukemia (ALL) has been
reported to be approximately 35% to 50%, even after allogeneic stem cell
transplantation (allo-SCT). We previously reported retrospective analyses of a
conditioning regimen of medium-dose etoposide, cyclophosphamide (CY), and total
body irradiation (TBI) before allo-SCT for ALL. To prospectively analyze the
efficacy of this conditioning regimen, we conducted a trial prospectively.
METHODS: The eligibility criteria of this study were as follows: diagnosis of
ALL, aged between 15 and 50 years, in complete remission, and first SCT from HLA
serologically matched donor. The primary endpoint of this study was event-free
survival at 1 year after SCT, and the events were defined as death and relapse.
RESULTS: Fifty eligible patients were treated, and the median age of the patients
was 33.5 years. Nineteen patients were Philadelphia chromosome-positive, and 47
were in first complete remission at SCT. All patients achieved neutrophil
engraftment. Grade 3 to 4 acute graft-versus-host disease and extensive chronic
graft-versus-host disease developed in 4 patients and 18 patients, respectively.
No patient died within 100 days after SCT. One-year event-free survival was
76.0%, and 1-year overall survival was 80.0%. The cumulative incidences of
relapse and non-relapse mortality at 1-year after SCT were 10.0% and 14.0%,
respectively. CONCLUSIONS: Medium-dose etoposide + CY + TBI is an effective
conditioning before allo-SCT for adult patients with ALL, enabling good disease
control without an increase in nonrelapse mortality. A phase 3 trial comparing
this regimen with the standard CY + TBI regimen for adult patients with ALL is
warranted.
PMID- 27500215
TI - Atypical Hemolytic Uremic Syndrome Recurrence after Renal Transplantation: C3
Glomerulonephritis as an Initial Presentation.
AB - Risk for atypical hemolytic uremic syndrome (aHUS) recurrence after renal
transplantation is low with an isolated membrane cofactor protein mutation (MCP).
We report the case of a 32-year-old woman with a MCP who underwent kidney
transplantation with a good evolution at 12 months. At 15 and 35 months, 2
episodes of thrombotic microangiopathy (TMA), after a miscarriage and a
preeclampsia, were misinterpreted as triggered by tacrolimus. After each episode
however serum creatinine returned to baseline. Five years after transplantation,
she had a self-limited rhinosinusitis followed 3 weeks later by an oliguric renal
failure. Her complement profile was normal. Graft biopsy showed C3
glomerulonephritis with no "humps" on electron microscopy. No significant renal
function improvement followed methylprednisolone pulsing. A second biopsy showed
severe acute TMA lesions with C3 glomerular deposits. Despite weekly eculizumab
for 1 month, dialysis was resumed. A new workup identified the "at-risk"
complement factor H haplotype. Thus, aHUS recurrence should be ruled out in aHUS
patients considered at low recurrence risk when a TMA is found in graft biopsy.
Prompt eculizumab therapy should be considered to avoid graft loss as aHUS
recurrence can first present as a C3 glomerulonephritis.
PMID- 27500216
TI - Rhodococcus equi Sepsis in a Renal Transplant Recipient: A Case Study.
AB - Rhodococcus equi is an unusual cause of infection in humans, but has emerged as
an opportunistic pathogen among immunocompromised patients. Primary pulmonary
involvement is the most common clinical presentation, although the spectrum of
disease is broad. Diagnosing R. equi infections remains challenging, both from
clinical and microbiological view, and no standard treatment has been
established. In this report, we present a detailed case of a 57-year-old male
renal transplant recipient who developed R. equi bacteremia with a concomitant
Pneumocystis jirovecii pneumonia. We describe the clinical features of R. equi
infections, highlight the importance of an early diagnosis, and briefly review
treatment options for this rare infection.
PMID- 27500217
TI - Immunodiagnostic Tests' Predictive Values for Progression to Tuberculosis in
Transplant Recipients: A Prospective Cohort Study.
AB - BACKGROUND: Little is known about the predictive value for progression to
tuberculosis (TB) of interferon-gamma release assays and how they compare with
the tuberculin skin test (TST) in assessing the risk of TB infection in
transplant recipients. METHODS: We screened 50 liver transplant (LT) and 26
hematopoietic stem cell transplant (HSCT) recipients with both QuantiFERON-TB
Gold In-tube (QFT-GT) and TST and prospectively followed them for a median of 47
months without preventive chemoprophylaxis. RESULTS: In the LT cohort, 1 in 22
(4.5%) QFT-GT-positive patients developed posttransplant TB, compared with none
of the QFT-GT-negative patients. In the HSCT cohort, none of the 7 QFT-GT
positive patients developed TB, whereas 1 case (5.3%) progressed to active TB
among the 19 QFT-GT-negative patients. Comparable results were obtained with the
TST: in the LT group, 1 of 23 TST-positive and none of the 27 TST-negative
patients developed TB; and in the HSCT group, none of the 8 TST-positive and one
of the 18 TST-negative patients progressed to active TB. CONCLUSIONS: In this
cohort of transplant recipients, the positive predictive value of QFT-GT for
progression to active TB was low and comparable to that of TST. Although the risk
of developing TB in patients with negative results at baseline is very low, some
cases may still occur.
PMID- 27500218
TI - Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Liver
Fibrosis in Rats.
AB - Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative
medicine. Recently, several studies have shown that MSCs can be easily isolated
from human amnion. In this study, we investigated the therapeutic effect of
transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver
fibrosis. METHODS: Liver fibrosis was induced by an intraperitoneal injection of
2 mL/kg of 50% carbon tetrachloride twice a week for 6 weeks. At 3 weeks, hAMSCs
(1 * 10(6) cells) were transplanted intravenously. Rats were sacrificed at 7
weeks, and histological analyses and quantitative reverse-transcription
polymerase chain reaction were performed. In vitro experiments were conducted to
investigate the effect of hAMSCs on the activation of Kupffer cells. RESULTS:
Transplantation of hAMSCs significantly reduced the fibrotic area, deposition of
type-I collagen, the number of alpha-smooth muscle actin-positive hepatic
stellate cells, and CD68-positive Kupffer cells in the livers. messenger RNA
expression of alpha-smooth muscle actin and tissue inhibitor of metalloproteinase
1 was significantly decreased and the expression of matrix metalloproteinase-9
and hepatocyte growth factor was significantly increased in the liver of hAMSC
treated rats. Transplantation of hAMSCs at 3 weeks plus 5 weeks did not have an
additive effect. In vitro experiments demonstrated that Kupffer cell activation
induced by lipopolysaccharide was significantly decreased by culturing with
conditioned medium obtained from hAMSCs. CONCLUSIONS: Transplantation of hAMSCs
provided significant improvement in a rat model of liver fibrosis, possibly
through the inhibition of Kupffer cell and hepatic stellate cell activation.
hAMSCs may be a potential new treatment for liver fibrosis.
PMID- 27500219
TI - A Phased Desensitization Protocol With Rituximab and Bortezomib for Highly
Sensitized Kidney Transplant Candidates.
AB - Desensitization protocols comprising plasmapheresis, IVIGs, and rituximab and/or
bortezomib have allowed for successful kidney transplantation in some highly HLA
sensitized patients with end-stage renal disease. However, the optimal
combination of these therapies and their proper timing remains entirely unknown.
We propose a phased desensitization strategy using rituximab followed by
bortezomib as a safer method. METHODS: Three sensitized kidney transplant
candidates who could not be desensitized using our conventional protocol, which
consists of a single rituximab dose combined with plasmapheresis, were enrolled
in this study. When IgM(+) CD27(-) naive B cells reappeared but IgM(+) CD27(+)
memory B cells remained undetectable in their peripheral blood, the patients were
treated with 1 cycle of bortezomib followed by plasmapheresis. RESULTS: After
bortezomib treatment, patients' donor-specific anti-HLA antibodies (DSA) values
were decreased, and cross-match tests were consistently negative. All 3 patients
underwent living donor kidney transplantation. They showed immediate renal
function, and both DSA and non-DSA were undetectable during the observation
period. Neither antibody-mediated rejection nor severe acute cellular rejection
was encountered in these patients after transplantation. CONCLUSIONS: The present
cases suggest that a phased use of rituximab and bortezomib can safely
desensitize highly sensitized kidney transplant candidates.
PMID- 27500220
TI - Functional Implications of Biochemical and Molecular Characteristics of Donation
After Circulatory Death Livers.
AB - In aggregate, livers donated after circulatory death (DCD) provide lower rates of
graft and patient survival compared to brain dead donors (DBD). A method to
identify DCD livers likely to perform well would lead to better decision-making
regarding which livers to use and which to discard and is an important unmet
clinical need. We hypothesized that the ischemic time between extubation and cold
perfusion in the donor leads to immediate and unique biochemical and molecular
changes that could be used to predict subsequent function. METHODS: Biopsies from
normal perfused liver, immediately after cold perfusion during DCD or DBD liver
procurement, and during subsequent cold storage were analyzed and compared.
Biochemical analysis included adenosine triphosphate (ATP), adenosine
diphosphate, adenosine monophosphate, hypoxanthine, xanthine, inosine,
nicotinamide adenine dinucleotide, and flavin adenine dinucleotide. Levels of
these metabolites were compared to peak posttransplant aspartate aminotransferase
as a marker of ischemic injury. Molecular analysis was performed by
transcriptional profiling using high throughput sequencing. RESULTS: Immediately
after cold perfusion in the donor, biochemical analysis revealed lower levels of
ATP and adenosine diphosphate in DCD versus DBD liver samples (P < 0.01 in both
cases). The ATP levels showed high negative correlation with peak aspartate
aminotransferase levels in recipients (P = 0.029). Four hundred seventy genes
showed differential expression in DCD but not DBD samples immediately after cold
perfusion compared with normal liver samples. Upregulated genes function in
inflammation and immunity, whereas downregulated genes function in translation.
During cold storage, samples were transcriptionally inactive with no consistent
changes in messenger RNA expression. CONCLUSION: The ATP content of liver samples
taken immediately postperfusion correlates with ischemic injury. Transcriptional
profiling identifies biological process that may be relevant for enhancing
function in DCD liver transplantation. Transcriptional inactivity of cold stored
samples suggests messenger RNA levels over time are unlikely to provide
prognostic data.
PMID- 27500221
TI - Clostripain, the Missing Link in the Enzyme Blend for Efficient Human Islet
Isolation.
AB - Effective digestive enzymes are crucial for successful islet isolation.
Supplemental proteases are essential as they synergize with collagenase for
effective pancreas digestion. The presence of tryptic-like activity has been
implicated in efficient enzyme blends and the present study aimed to evaluate if
addition of clostripain, an enzyme with tryptic-like activity, could improve
efficacy of the islet isolation procedure. METHODS: Clostripain was added to the
enzyme blend just before pancreas perfusion. Islets were isolated per standard
method and numerous isolation parameters, islet quality control, and the number
of isolations fulfilling standard transplantation criteria were evaluated. Two
control organs per clostripain organ were chosen by blindly matching against body
mass index, cold ischemia time, hemoglobin A1c, donor sex, and donor age.
RESULTS: There were no differences in pancreas weight, dissection time, digestion
time, harvest time, percent digested pancreas, or total pellet volume before
islet purification between control or clostripain pancreases. Glucose-stimulated
insulin release results were similar between groups. Total isolation islet
equivalents, purified tissue volume and islet equivalents/g pancreas as well as
fulfillment of transplantation criteria favored clostripain processed pancreases.
CONCLUSIONS: The addition of clostripain to the enzyme blend soundly improved
islet yields and transplantation rates. It gently aided pancreas digestion and
maintained proper islet functionality. The addition of clostripain to the enzyme
blend has now been implemented into standard isolation protocols at the isolation
centers in Uppsala and in Oslo.
PMID- 27500222
TI - Patterns of Immune Regulation in Rhesus Macaque and Human Families.
AB - Naturally acquired immune regulation amongst family members can result in mutual
regulation between living related renal transplant donor and recipients.
Pretransplant bidirectional regulation predisposed to superior renal allograft
outcome in a CAMPATH-1H protocol. We tested whether Rhesus macaques, a large
animal model of choice for preclinical transplant studies, share these
immunoregulatory properties. METHODS: Antigen-specific linked suppression was
measured by trans vivo delayed-type hypersensitivity [tvDTH] response.
Neutralizing antibodies to regulatory cytokines, IL-10, TGF-beta, and IL-35 were
coinjected to ascertain the role of these cytokines in the regulatory response.
RESULTS: Peripheral blood mononuclear cells (PBMC) of 116 Rhesus macaques in 50
families and 78 human subjects in 25 families were analyzed. Suppression of the
recall response of 25% or greater was detected in 30 of 51 (59%) monkeys, and 25
of 36 (69%) human subjects when PBMC were coinjected with antigens of the mother,
containing the noninherited maternal antigens. In 33% of Rhesus and 32% of human
subjects, linked suppression was also seen when PBMC from the mother was assayed
with antigens from offspring. Bidirectional regulation was also seen between
greater than 50% of the major histocompatibility complex (MHC)-identical full
siblings; subcellular antigens caused significant linked suppression in 7 of 10
(Rhesus) and 8 of 15 (human) cases, indicating the importance of familial minor H
antigens. The lowest incidence of regulation was seen in MHC-1 haplotype
mismatched siblings in both species. Linked suppression was most effectively
reversed by antibodies that neutralized TGFbeta1, and the 2 subunits of IL-35
(Ebi3 and IL12p35). CONCLUSIONS: Rhesus macaques provide a suitable model for
analyzing the impact of bidirectional regulation in living related donor
recipient pairs.
PMID- 27500223
TI - Sofosbuvir and Simeprevir Therapy for Recurrent Hepatitis C Infection After Liver
Transplantation.
AB - Antiviral therapy for recurrent hepatitis C in liver transplant recipients has
been associated with low efficacy, poor tolerability, and drug-drug interactions.
Recent approval of various hepatitis C direct-acting antivirals has resulted in
improvement of these parameters. We evaluated the efficacy and safety of 12 week
all-oral interferon- and ribavirin-free therapy with sofosbuvir and simeprevir.
METHODS: Thirty-two genotype 1 liver transplant recipients with recurrent
hepatitis C infection were retrospectively analyzed. All patients received 12
weeks of sofosbuvir 400 mg and simeprevir 150 mg orally daily. The primary
endpoint was sustained virologic response 12 weeks after treatment. RESULTS:
Sustained virologic response 12 weeks after treatment was achieved in 30 of 32
(94%; 95% confidence interval, 79-99%) patients. All patients enjoyed on
treatment virological response. Both patients who relapsed were cirrhotic,
previously treated with Q80K polymorphism. Significant improvements in alkaline
phosphatase, albumin, alanine aminotransferase levels, and platelets were seen at
12-week post therapy. Treatment was well tolerated. No grade 3 or 4 adverse
events were noted. Headache and fatigue were the most common complaints.
CONCLUSION: Combination of sofosbuvir and simeprevir for 12 weeks resulted in 94%
sustained virological response-12 rates in patients with hepatitis C genotype 1
and was well tolerated.
PMID- 27500224
TI - Successful Combined Pancreas Fourth-Kidney Third and Pancreas Third-Kidney Second
Transplantation: A Case Report.
AB - Extremely few reports have been published on experience with multiple combined
pancreas-kidney re-transplantation including long-term results. We here analyze
our experience with two patients following successful combined pancreas fourth
kidney third and pancreas third-kidney second transplantation. METHODS: Patient
and graft survival as well as graft function and major complications were
recorded. Patient 1 (women, 47 years) underwent combined pancreas fourth-kidney
third transplantation after previous removal of the first and second renal and
the second pancreatic grafts. Patient 2 (men, 51 years) underwent combined
pancreas third-kidney second transplantation after nephrectomy of the first renal
graft. Immunosuppression consisted of induction with alemtuzumab and maintenance
with tacrolimus, mycophenolate mofetil/mycophenolic acid and steroids. RESULTS:
After a follow-up of 44 and 49 months, respectively, both patients are doing well
with stable graft function. Leukopenia, thrombocytopenia, bacterial sepsis, and
chronic hepatitis C as major complications were controllable. CONCLUSIONS:
Multiple pancreas-retransplantations combined with simultaneous renal
transplantation are feasible. Meticulous immunosuppression, careful monitoring,
and excellent patient adherence are of crucial importance.
PMID- 27500225
TI - Kidneys From alpha1,3-Galactosyltransferase Knockout/Human Heme Oxygenase-1/Human
A20 Transgenic Pigs Are Protected From Rejection During Ex Vivo Perfusion With
Human Blood.
AB - Multiple modifications of the porcine genome are required to prevent rejection
after pig-to-primate xenotransplantation. Here, we produced pigs with a knockout
of the alpha1,3-galactosyltransferase gene (GGTA1-KO) combined with transgenic
expression of the human anti-apoptotic/anti-inflammatory molecules heme oxygenase
1 and A20, and investigated their xenoprotective properties. METHODS: The GGTA1
KO/human heme oxygenase-1 (hHO-1)/human A20 (hA20) transgenic pigs were produced
in a stepwise approach using zinc finger nuclease vectors targeting the GGTA1
gene and a Sleeping Beauty vector coding for hA20. Two piglets were analyzed by
quantitative reverse-transcription polymerase chain reaction, flow cytometry, and
sequencing. The biological function of the genetic modifications was tested in a
(51)Chromium release assay and by ex vivo kidney perfusions with human blood.
RESULTS: Disruption of the GGTA1 gene by deletion of few basepairs was
demonstrated in GGTA1-KO/hHO-1/hA20 transgenic pigs. The hHO-1 and hA20 mRNA
expression was confirmed by quantitative reverse-transcription polymerase chain
reaction. Ex vivo perfusion of 2 transgenic kidneys was feasible for the maximum
experimental time of 240 minutes without symptoms of rejection. CONCLUSIONS:
Results indicate that GGTA1-KO/hHO-1/hA20 transgenic pigs are a promising model
to alleviate rejection and ischemia-reperfusion damage in porcine xenografts and
could serve as a background for further genetic modifications toward the
production of a donor pig that is clinically relevant for xenotransplantation.
PMID- 27500226
TI - Medium-Term Renal Function in a Large Cohort of Stable Kidney Transplant
Recipients Converted From Twice-Daily to Once-Daily Tacrolimus.
AB - BACKGROUND: There is some evidence pointing toward better renal function in
kidney transplant recipients (KTR) treated with once-daily tacrolimus (QD-TAC)
vs. twice-daily tacrolimus (BID-TAC). METHODS: This is an extension study of a 1
year, single arm prospective study of stable KTR who were converted from BID-TAC
to QD-TAC (4.9 +/- 4.0 years after transplantation) in Spanish routine clinical
practice. Patient and graft survival, renal function, acute rejection episodes,
and other analytic parameters were assessed at 24 and 36 months after conversion.
RESULTS: A total of 1798 KTR were included in the extension study. Tacrolimus
doses at 36 months were significantly lower compared to those at time of
conversion (-0.2 mg/day; P = 0.023). Blood levels were lower than baseline during
all the study (P < 0.001). Graft and patient survival at 3 years after conversion
were 93.9% and 95.1%, respectively. Compared with baseline, the mean estimated
glomerular filtration rate (eGFR) remained very stable at all timepoints (56.7 +/
19.8 vs 58.1 +/- 24.6 mL/min per 1.73 m(2) at month 36; P = 0.623). Even when
patients reinitiating dialysis were counted as eGFR = 0, the mean eGFR was very
stable. In fact, a small but significant increase was observed at 36 months
versus baseline (+0.1 mL/min per 1.73 m(2); P = 0.025). An increase in
proteinuria was observed at 36 months versus baseline (+0.11 g/24 h; P < 0.001).
Acute rejection rates were low during the study. CONCLUSIONS: Conversion from BID
TAC to QD-TAC in a large cohort of stable KTR was safe and associated with a very
stable renal function after 3 years. Comparative studies are warranted to assess
the feasibility of such conversion.
PMID- 27500228
TI - Skin Cancer in the Crosshairs: Highlights from the Biennial Scientific Retreat of
International Transplant Skin Cancer Collaborative and Skin Care in Organ
Transplant Recipients Europe.
AB - The International Transplant Skin Cancer Collaborative (ITSCC) is an organization
comprising of physicians; transplant surgeons and basic science research
scientists dedicated in providing optimal care and ongoing research advancements
in solid organ transplant recipients to improve patient outcome and quality of
life. As medical advances occur, it is anticipated that the sheer number of solid
organ transplantations occurring worldwide will continue to increase. The long
term medication associated immunosuppression improves graft survival, but as a
consequence, these individuals become increasingly susceptible to various
cutaneous malignancies, lymphoproliferative disorders and infections. Squamous
cell carcinoma is the most frequently encountered skin cancer and increases 65-
to 250-fold [Jensen et al., Skin cancer in kidney and heart transplant recipients
and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol.
1999;40:177-186; Lindelof et al., Incidence of skin cancer in 5356 patients
following organ transplantation. Br J Dermatol. 2000; 143:513-519]. However, the
rates of basal cell carcinoma, Merkel cell carcinoma and melanoma also increase
in organ transplant recipients leading to significant morbidity as well as
mortality [Berg and Otley. Skin cancer in organ transplant recipients:
epidemiology, pathogenesis, and management. J Am Acad Dermatol. 2002; 47:1-20].
In October 2014, the International Transplant Skin Cancer Collaborative and its
equivalent European counterpart, Skin Care in Organ Transplant Recipients Europe
held its 10th biennial meeting in Essex, MA to discuss the clinical conundrums
and the evolving research pertinent to the field. This meeting report provides a
synthesis of all the clinical and research data presented at the 4-day meeting.
PMID- 27500227
TI - HLA Associations and Risk of Posttransplant Lymphoproliferative Disorder in a
Danish Population-Based Cohort.
AB - BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a feared
complication to organ transplantation, associated with substantial morbidity and
inferior survival. Risk factors for PTLD include T cell-depleting induction
therapy and primary infection or reactivation of Epstein-Barr virus. Possible
associations between certain HLA types and the risk of developing PTLD have been
reported by other investigators; however, results are conflicting. METHODS: We
conducted a retrospective, population-based study on 4295 Danish solid organ
transplant patients from the Scandiatransplant database. Having identified 93
PTLD patients in the cohort, we investigated the association of HLA types with
PTLD, Epstein-Barr virus status and time to PTLD onset. The outcomes survival and
PTLD were evaluated using Cox regression; mismatching, and the PTLD-specific
mortality were evaluated in a competing risk analysis. RESULTS: Risk of PTLD was
associated with male sex (odds ratio, 1.70; 95% confidence interval, 1.07-2.71),
and, in women, HLA-DR13 conferred an increased risk (odds ratio, 3.22; 95%
confidence interval, 1.41-7.31). In multivariate analysis, HLA-B45 and HLA-DR13
remained independent predictive factors of PTLD. Mismatching in the B locus was
associated with a reduced risk of PTLD (P < 0.001). Overall survival was poor
after a PTLD diagnosis and was significantly worse than that in the remaining
transplant cohort (P < 0.001). CONCLUSIONS: Our data indicate risk-modifying HLA
associations, which can be clinically useful after transplantation in
personalized monitoring schemes. Given the strong linkage disequilibrium in the
HLA region, the associations must be interpreted carefully. The large size,
virtually complete ascertainment of cases and no loss to follow-up remain
important strengths of the study.
PMID- 27500229
TI - Hispanic/Latino Disparities in Living Donor Kidney Transplantation: Role of a
Culturally Competent Transplant Program.
AB - Hispanic Americans face disparities in access to kidney transplantation,
particularly living donor kidney transplantation (LDKT). This study compared
characteristics of LDKT recipients before and after implementing the Hispanic
Kidney Transplant Program (HKTP) at Northwestern Medicines (NM) and other
centers. METHODS: The NM HKTP, initiated in December 2006, delivers culturally
and linguistically competent and congruent care. Program-specific data were used
to compare the mean ratios of Hispanic to non-Hispanic white LDKTs between pre
HKTP (2001-2006) and post-HKTP (2008-2013), and to compare the characteristics of
NM's adult LDKT patients between pre-HKTP and post-HKTP. The same ratio was
calculated for transplant centers in regions with a significant Hispanic
population (>=25%) and performing in the top tertile of total LDKT volume in the
pre-HKTP period. The number of Hispanic and non-Hispanic white patients added to
the waiting list were compared between pre-HKTP (2001-2006) and post-HKTP (2008
2013) as a proxy for increased patient referrals and a pathway by which the HKTP
may increase LDKTs. RESULTS: The ratio of Hispanic to non-Hispanic white LDKTs
significantly increased by 70% after the implementation of NM's HKTP (pre-HKTP
mean = 0.20, post-HKTP mean = 0.34; P= 0.001). None of the other transplant
centers experienced a similar increase in their ratio of Hispanic to non-Hispanic
white LDKTs. The NM waiting list additions grew by 91% among Hispanics, but grew
only 4% for non-Hispanic whites. CONCLUSIONS: These data suggest that the
development and implementation of a culturally congruent transplant program can
positively affect Hispanic LDKT and thereby reduce Hispanics disparities in LDKT
rates. Further studies are needed to prospectively evaluate the generalizability
of implementing such culturally competent interventions at other transplant
programs.
PMID- 27500230
TI - Should We Exclude Live Donor Liver Transplantation for Liver Transplant
Recipients Requiring Mechanical Ventilation and Intensive Care Unit Care?
AB - Patients with acute and chronic liver disease often require admission to
intensive care unit (ICU) and mechanical ventilation support before liver
transplantation (LT). Rapid disease progression and high mortality on LT waiting
lists makes live donor LT (LDLT) an attractive option for this patient
population. METHODS: During 2000 to 2011, all ICU-bound and mechanically
ventilated patients receiving an LDLT (n = 7) were compared to patients receiving
a deceased donor LT (DDLT) (n = 38). RESULTS: Both groups were comparable
regarding length of pretransplant ICU stay (DDLT: 2 [1-31] days vs LDLT: 2 [1-8]
days; P = 0.2), days under mechanical ventilation (DDLT: 2 [1-31] days vs LDLT: 2
[1-5] days; P = 0.2), pretransplant dialysis (DDLT: 45% vs LDLT: 43%; P = 1) and
model for end-stage liver disease score (DDLT: 33 +/- 8 vs LDLT: 33 +/- 10; P =
0.911). Live donors median evaluation time was 24 hours (18-561 hours). As
expected, median time on waiting list was significantly lower in the LDLT group
(DDLT: 13 [0-1704] days vs LDLT: 10 [1-33] days; P = 0.008). Incidence of
postoperative complications was numerically, albeit not significantly higher in
the DDLT versus LDLT (68% vs 29%; P = 0.08). No difference was detected between
LDLT and DDLT patients regarding 1-year (DDLT: 76% vs LDLT: 85%), 3-year (DDLT:
68% vs LDLT: 85%), and 5-year (DDLT: 68% vs LDLT: 85%) graft and patient
survivals (P = 0.41). No severe donor complication occurred after live donation.
CONCLUSIONS: The LDLT may provide a faster access to transplantation and
therefore, offers an alternative treatment option for critically ill patients
requiring ICU care and mechanical ventilation support at the time of
transplantation.
PMID- 27500231
TI - Prediction of Long-term Renal Allograft Outcome By Early Urinary CXCL10 Chemokine
Levels.
AB - Predictive biomarkers for long-term renal allograft outcome could help to
individualize follow-up strategies and therapeutic interventions. METHODS: We
investigated the predictive value of urinary CXC chemokine ligand 10 (CXCL10)
measured at different timepoints (ie, at 3 and 6 months, and mean of 3 and 6
months coined CXCL10-burden) for long-term allograft outcomes in 154 patients.
The primary outcome was a composite graft endpoint of death-censored allograft
loss and/or biopsy-proven rejection and/or decline of estimated glomerular
filtration rate greater than 20% occurring beyond 6 months after transplantation.
RESULTS: After a median follow-up of 6.6 years (interquartile range, 5.7-7.5
years) the endpoint was reached in 43/154 patients (28%). In a multivariable Cox
regression model independent predictors were 6-month CXCL10 levels, the CXCL10
burden, HLA-mismatches, donor age and delayed graft function while previous
(sub)clinical rejection, estimated glomerular filtration rate and proteinuria at
6 months, as well as 3-month CXCL10 levels were not. Time-dependent receiver
operating characteristic analysis revealed an area under the curve of 0.68 (6
month CXCL10) and 0.67 (CXCL10-burden). Grouped by optimal cutoff, low 6-month
CXCL10 (<0.70 ng/mmol) was associated with a 95% endpoint-free 5-year survival
compared to 78% with high 6-month CXCL10 (P = 0.0007). Only 2 of 62 patients (3%)
with low 6-month CXCL10 levels (<0.70 ng/mmol) experienced late rejection or
graft loss due to rejection compared to 15 of 92 patients (16%) with high 6-month
CXCL10 levels (P = 0.008). Similar results were obtained when patients were
grouped according to CXCL10-burden (cutoff, 1.06 ng/mmol). CONCLUSIONS: Six-month
urinary CXCL10 is an independent predictor for long-term graft outcome and thus
might be a supplementary tool to tailor surveillance strategies and therapy.
PMID- 27500232
TI - Laser Ablation Inductively Coupled Plasma Mass Spectrometry: An Emerging
Technology for Multiparametric Analysis of Tissue Antigens.
AB - New analytical techniques for multiparametric characterisation of individual
cells are likely to reveal important information about the heterogeneity of
immunological responses at the single-cell level. In this proof-of-principle
study, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS)
was applied to the problem of concurrently detecting 24 lineage and activation
markers expressed by human leucocytes. This approach was sufficiently sensitive
and specific to identify subpopulations of isolated T, B, and natural killer
cells. Leucocyte subsets were also accurately detected within unfractionated
peripheral blood mononuclear cells preparations. Accordingly, we judge LA-ICP-MS
to be a suitable method for assessing expression of multiple tissue antigens in
solid-phase biological specimens, such as tissue sections, cytospins, or cells
grown on slides. These results augur well for future development of LA-ICP-MS
based bioimaging instruments for general users.
PMID- 27500233
TI - Subzero 12-hour Nonfreezing Cryopreservation of Porcine Heart in a Variable
Magnetic Field.
AB - BACKGROUND: A novel subzero nonfreezing heart preservation method has been
developed. It uses a refrigerating device that generates a variable magnetic
field, allowing the whole organ to be cooled simultaneously to a supercooled
state without the use of cryoprotectant. As a fundamental experiment for heart
preservation, we verified whether this novel method is able to suppress anaerobic
metabolism and reduce damage in the hearts of large animals. METHODS: Twelve
porcine hearts were collected and preserved for 12 hours using a simple immersion
method. The hearts were divided into 2 groups: 6 underwent nonfreezing
preservation at -3 degrees C in a variable magnetic field (subzero group), and 6
underwent conventional preservation at 4 degrees C (conventional group). The
quantity of anaerobic metabolism and the degree of ultrastructural change in the
2 groups were evaluated and compared. RESULTS: The concentration of adenosine
triphosphate in the myocardial tissue was significantly greater in the subzero
group than in the conventional group (21.06+/-5.87 MUmol/g vs 5.96+/-3.41
MUmol/g; P < 0.05). The accumulated lactate concentration was significantly lower
in the subzero group than in the conventional group (6.58+/-2.28 MUmol/g vs
11.15+/-3.74 MUmol/g; P < 0.05). The Flameng score, an index of ultrastructural
changes to the mitochondria, was significantly lower in the subzero group than in
the conventional group (1.28+/-0.40 vs 2.73+/-0.30; P < 0.05). CONCLUSIONS:
Subzero nonfreezing preservation using a variable magnetic field resulted in a
remarkable suppression of anaerobic metabolism and myocardial protection in
porcine hearts.
PMID- 27500234
TI - First Robotic-Assisted Dual Kidney Transplant: Surgical Technique and Report of a
Case With 24-month Follow-up.
AB - BACKGROUND: Open surgery is the gold standard procedure for kidney
transplantation. There is a strong rationale for using minimally invasive surgery
in patients with end-stage renal disease. A robotic-assisted dual kidney
transplant was performed for the first time at our institution. METHODS: In
August 2013, a 63-year-old man with end-stage renal disease and diabetes mellitus
under pharmacological control received both kidneys from a 70-year-old marginal
donor. Pretransplant donor biopsy demonstrated a bilateral Karpinski score
greater than 5. The organs did not exhibit malformations and each had an artery
and a vein. The procedure was carried out by a 7-port intraperitoneal approach
using the da Vinci surgical system. The procedure was identical for the 2 kidneys
except that mobilization of the sigmoid colon was required to introduce the left
graft. The renal vessels were anastomosed to the left external iliac vessels. The
novel aspect of the technique was the introduction of both grafts through a
single, 7-cm upper midline incision. RESULTS: Total operative time was 400
minutes and blood loss was 120 mL. Both grafts immediately began functioning.
There were no intraoperative or postoperative complications. The patient was
discharged on the seventh postoperative day with normal renal function. At 24
months, he is well and does not require hemodialysis. CONCLUSIONS: Minimally
invasive robotic-assisted technology is a promising technique that provides
exceptional patient outcomes by reducing operative morbidity, immobilization, and
time to recovery, while affording better esthetic results. Selected patients with
multiple comorbidities benefit most. Grafts from marginal donors are an extremely
valuable resource.
PMID- 27500235
TI - The Role of Lysophosphatidic Acid on Airway Epithelial Cell Denudation in a
Murine Heterotopic Tracheal Transplant Model.
AB - BACKGROUND: Chronic rejection is the major leading cause of morbidity and
mortality after lung transplantation. Obliterative bronchiolitis (OB), a
fibroproliferative disorder of the small airways, is the main manifestation of
chronic lung allograft rejection. However, there is currently no treatment for
the disease. We hypothesized that lysophosphatidic acid (LPA) participates in the
progression of OB. The aim of this study was to reveal the involvement of LPA on
the lesion of OB. METHODS: Ki16198, an antagonist specifically for LPA1 and LPA3,
was daily administered into the heterotopic tracheal transplant model mice at the
day of transplantation. At days 10 and 28, the allografts were isolated and
evaluated histologically. The messenger RNA levels of LPAR in microdissected
mouse airway regions were assessed to reveal localization of lysophosphatidic
acid receptors. The human airway epithelial cell was used to evaluate the
mechanism of LPA-induced suppression of cell adhesion to the extracellular matrix
(ECM). RESULTS: The administration of Ki16198 attenuated airway epithelial cell
loss in the allograft at day 10. Messenger RNAs of LPA1 and LPA3 were detected in
the airway epithelial cells of the mice. Lysophosphatidic acid inhibited the
attachment of human airway epithelial cells to the ECM and induced cell
detachment from the ECM, which was mediated by LPA1 and Rho-kinase pathway.
However, Ki16198 did not prevent obliteration of allograft at day 28.
CONCLUSIONS: The LPA signaling is involved in the status of epithelial cells by
distinct contribution in 2 different phases of the OB lesion. This finding
suggests a role of LPA in the pathogenesis of OB.
PMID- 27500237
TI - Tacrolimus-Induced Salt Losing Nephropathy Resolved After Conversion to
Everolimus.
PMID- 27500236
TI - Renal Function in Kidney and Liver Transplant Recipients After A 130-km Road
Cycling Race.
AB - BACKGROUND: A few patients, after receiving solid organ transplantation, return
to performing various sports and competitions; however, at present, data no study
had evaluated the effects of endurance cycling races on their renal function.
METHODS: Race times and short form (36) health survey questionnaires of 10 kidney
transplant recipients (KTR) and 8 liver transplant recipients (LTR) transplanted
recipients involved in a road cycling race (130 km) were compared with 35 healthy
control subjects (HCS), also taking laboratory blood and urine tests the day
before the race, at the end of the race, and 18 to 24 hours after competing.
RESULTS: The 3 groups showed similar race times (KTR, 5 hours 59 minutes +/- 0
hours 39 minutes; LTR, 6 hours 20 minutes +/- 1 hour 11 minutes; HCS, 5 hours 40
minutes +/- 1 hour 28 minutes), similar short form (36) health survey scores, and
similar trend of laboratory parameters which returned to baseline after 18 to 24
hours. After the race, there was an increase in creatinine (0.24 mg/dL; effect
size [ES] = 0.78; P < 0.001), urea (22 mg/dL; ES = 1.42; P < 0.001), and a
decrease of estimated glomerular filtration rate (-17 mL/min; ES = 0.85; P <
0.001). The increase of blood uric acid was more remarkable in HCS and KTR (2.3
mg/dL; ES = 1.39; P < 0.001). The KTR showed an increase of microalbuminuria
(167.4 mg/L; ES = 1.20; P < 0.001) and proteinuria (175 mg/mL; ES = 0.97; P <
0.001) similar to LTR (microalbuminuria: 176.0 mg/L; ES = 1.26; P < 0.001;
proteinuria: 213 mg/mL; ES = 1.18; P < 0.001), with high individual variability.
The HCS had a nonsignificant increase of microalbuminuria (4.4 mg/L; ES = 0.03; P
= 0.338) and proteinuria (59 mg/mL; ES = 0.33; P = 0.084). CONCLUSIONS: Selected
and well-trained KTR and LTR patients can participate to an endurance cycling
race showing final race times and temporary modifications of kidney function
similar to those of HCS group, despite some differences related to baseline
clinical conditions and pharmacological therapies. Patients involved in this
study represent the upper limit of performance currently available for transplant
recipients and cannot be considered representative of the entire transplanted
population.
PMID- 27500238
TI - Analysis of the Influence of HLA-A Matching Relative to HLA-B and -DR Matching on
Heart Transplant Outcomes.
AB - BACKGROUND: There are conflicting reports on the effect of donor-recipient HLA
matching on outcomes in heart transplantation. The objective of this study was to
investigate the effects of HLA-A matching relative to HLA-B and -DR matching on
long-term survival in heart transplantation. METHODS: A total of 25 583 patients
transplanted between 1988 and 2011 were identified from the International Society
for Heart and Lung Transplantation registry. Transplants were divided into 2
donor-recipient matching groups: HLA-A-compatible (no HLA-A mismatches) and HLA-A
incompatible (1-2 HLA-A mismatches). Primary outcome was all-cause mortality.
Secondary outcomes were graft failure-, cardiovascular-, infection-, or
malignancy-related deaths. RESULTS: The risk of all-cause mortality 15 years
after transplantation was higher for HLA-A-compatible (vs HLA-A-incompatible)
grafts in patients who had HLA-B-, HLA-DR-, or HLA-B,DR-incompatible grafts (P =
0.027, P = 0.007, and P = 0.002, respectively) but not in HLA-B- and/or HLA-DR
compatible grafts. This was confirmed in multivariable Cox regression analysis
where HLA-A compatibility (vs HLA-A incompatibility) was associated with higher
mortality in transplants incompatible for HLA-DR or HLA-B and -DR (hazard ratio
[HR], 1.59; 95% confidence interval [95% CI], 1.11-2.28; P = 0.012 and HR, 1.69;
95% CI, 1.17-2.43; P = 0.005, respectively). In multivariable analysis, the
largest compromise in survival for HLA-A compatibility (vs HLA-incompatibility)
was for chronic rejection in HLA-B- and -DR-incompatible grafts (HR, 1.91; 95%
CI, 1.22-3.01; P = 0.005). CONCLUSIONS: Decreased long-term survival in heart
transplantation was associated with HLA-A compatibility in HLA-B,DR-incompatible
grafts.
PMID- 27500239
TI - Indications and Outcomes in Liver Transplantation in Patients With Primary
Sclerosing Cholangitis in Norway.
AB - BACKGROUND: Primary sclerosing cholangitis (PSC) is 1 of the leading causes of
liver transplantation (LTX) in Scandinavia, and an increasing number of PSC
patients have been transplanted in Norway during the last 2 decades. This trend
is partly attributable to the recently established practice in Norway of offering
LTX to PSC patients with cholangiocellular dysplasia. Based on the controversy
associated with this practice, we herein aimed to report the main features and
outcomes of our LTX program in PSC. METHODS: The primary indication for LTX
(quality of life/end-stage liver disease or suspected neoplasia) was
retrospectively determined for 222 patients undergoing LTX for PSC or other
autoimmune liver diseases (primary biliary cirrhosis/autoimmune hepatitis) with
at least 5 years of follow-up. RESULTS: In PSC patients impaired quality of life
(43.5%) and end-stage liver disease (38.4%) were the most frequent indications
for LTX, whereas suspected neoplasia accounted for 18.1%. The proportion of PSC
patients with manifest encephalopathy, variceal bleeding, or ascites declined
over time. In patients with suspected neoplasia as the primary indication for LTX
(n = 25), neoplasia was confirmed in the explanted liver in 20 patients (80%).
Five-year survival rates for PSC patients transplanted between 2001 and 2009 were
91.9% for patients receiving LTX due to impaired quality of life or end-stage
liver disease and 83.3% for suspected neoplasia. CONCLUSIONS: The PSC patients
are increasingly listed for LTX at an earlier stage of their liver disease. In
patients with suspected neoplasia before LTX, 5-year survival was acceptable,
despite confirmation of neoplasia in 80% of the liver explants.
PMID- 27500240
TI - Living Donor Liver Transplantation Using a Liver Graft With Congenital
Intrahepatic Portosystemic Shunt.
AB - Despite of recent development of imaging modalities, congenital intrahepatic
portosystemic shunt (IPSS) is rarely diagnosed. Therefore, living donor liver
transplantation using a liver graft with IPSS has not been previously published.
MATERIALS AND METHODS: We report a 28-year-old male patient with end-stage liver
disease secondary to Wilson disease. His 26-year-old brother was a potential
living donor, who had an IPSS of 25 mm in diameter at segment 6 as shown by
computed tomography. Liver function tests were normal, and blood ammonia
concentration was in the upper limit of normal. RESULTS: Living donor liver
transplantation was uneventfully performed. After surgery, a recipient liver
function tests showed a quick recovery, and serum ammonia levels were
consistently normal. Although thrombosis inside the IPSS was confirmed by
computed tomography on postoperative day 21, this thrombosis disappeared at 3
months posttransplant with anticoagulants. Currently (12 months posttransplant),
the patient has fully recovered, and the IPSS is still the same size.
CONCLUSIONS: Based on our experience, liver allografts with IPSS can be accepted
as potential liver allografts.
PMID- 27500241
TI - Comparison of Neutral Proteases and Collagenase Class I as Essential Enzymes for
Human Islet Isolation.
AB - Efficient islet isolation requires synergistic interaction between collagenase
class I (CI) and class II (CII). The CI degradation alters the ratio between CI
and CII and is responsible for batch-to-batch variations. This study compares the
role of neutral protease (NP) plus clostripain (CP) with CI as essential enzymes
for human islet isolation. METHODS: Human islets were isolated using 4 different
enzyme mixtures composed of CII plus either intact (CI-115) or degraded CI (CI
100). Blends were administered either with or without NP/CP. Purified islets were
cultured for 3 to 4 days before islet quality assessment. RESULTS: Whereas using
intact CI-115 without NP/CP did not significantly reduce islet yield (3429 +/-
631 vs 3087 +/- 970 islet equivalent/g, nonsignificant), administration of
degraded CI-100 without NP/CP decreased islet yield from 3501 +/- 580 to 1312 +/-
244 islet equivalent/g (P < 0.01), doubled the amount of undigested tissue from
11.8 +/- 1.6 to 24.4 +/- 1.2% (P < 0.01) and triplicated the percentage of
trapped islets from 7.7 +/- 2.8 to 22.5 +/- 3.6% (P < 0.05). Islet yield did not
vary between supplemented CI-115 and CI-100, but was increased using CI-115 when
NP/CP was omitted (P < 0.05). A trend toward higher viability and increased
secretory insulin response was noted in both CI-100 and CI-115 when NP/CP was not
added. CONCLUSIONS: This study suggests that NP/CP can compensate reduced CI
activity. Future attempts to optimize enzyme blends should consider the
possibility to increase the proportion of collagenase CI to reduce the need for
potentially harmful NPs.
PMID- 27500242
TI - Epstein-Barr Virus-Positive Posttransplant Lymphoproliferative Disease After
Solid Organ Transplantation: Pathogenesis, Clinical Manifestations, Diagnosis,
and Management.
AB - Posttransplant lymphoproliferative disease (PTLD) is a potentially fatal
complication after (solid organ) transplantation, which is highly associated with
Epstein-Barr virus (EBV). The EBV-specific cytotoxic T cell response that is
essential in controlling the virus in healthy individuals is suppressed in
transplant recipients using immunosuppressive drugs. A primary EBV infection in
EBV-seronegative patients receiving an EBV-seropositive donor organ or a
reactivation in those who are already latently infected pretransplantation can
lead to uninhibited growth of EBV-infected B cells and subsequently to PTLD.
Effective preventive strategies, such as vaccines and antiviral agents, are
lacking. Because not every transplant recipient with increasing EBV viral load
develops PTLD, it is hard to decide how intensively these patients should be
monitored and how and when a preemptive intervention should take place. There is
a need for other tools to help predict the development of PTLD in patients at
risk to make timing and strategy of preemptive intervention easier and more
reliable. The cornerstone of the treatment of patients with PTLD is restoring the
host's immunity by reduction of immunosuppressive drug therapy. American and
British guidelines recommend to add rituximab monotherapy or rituximab in
combination with cyclophosphamide, doxorubicin, vincristine, and prednisolone,
depending on histology and clinical characteristics. Although response to these
therapies is good, toxicity is a problem, and PTLD still has a relatively high
mortality rate. An evolving therapy, especially in PTLD occurring in allogeneic
stem cell transplantation, is restoring the host's immune response with infusion
of EBV-specific cytotoxic T cells. This may also play a role in the future in
both prevention and treatment of PTLD in SOT.
PMID- 27500243
TI - Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional
Fibrinogen: A Retrospective Observational Study.
AB - Patients undergoing orthotopic liver transplantation are at high risk of bleeding
complications. Several Authors have shown that thromboelastography (TEG)-based
coagulation management and the administration of fibrinogen concentrate reduce
the need for blood transfusion. METHODS: We conducted a single-center,
retrospective cohort observational study (Modena Polyclinic, Italy) on 386
consecutive patients undergoing liver transplantation. We assessed the impact on
resource consumption and patient survival after the introduction of a new TEG
based transfusion algorithm, requiring also the introduction of the fibrinogen
functional thromboelastography test and a maximum amplitude of functional
fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in
administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based
algorithm previously used (2005-2011, n = 268). RESULTS: After 2012, there was a
significant decrease in the use of homologous blood (1502 +/- 1376 vs 794 +/- 717
mL, P < 0.001), fresh frozen plasma (537 +/- 798 vs 98 +/- 375 mL, P < 0.001),
and platelets (158 +/- 280 vs 75 +/- 148 mL, P < 0.005), whereas the use of
fibrinogen increased (0.1 +/- 0.5 vs 1.4 +/- 1.8 g, P < 0.001). There were no
significant differences in 30-day and 6-month survival between the 2 groups.
CONCLUSIONS: The implementation of a new coagulation management method featuring
the addition of the fibrinogen functional thromboelastography test to the TEG
test according to an algorithm which provides for the administration of
fibrinogen has helped in reducing the need for transfusion in patients undergoing
liver transplantation with no impact on their survival.
PMID- 27500244
TI - Conservative Pancreas Graft Preservation at the Extreme.
AB - Because of the value some patients place in remaining insulin-independent after
pancreas transplantation, they may be reluctant to undergo graft pancreatectomy,
even in the face of extreme complications, such as graft thrombosis and duodenal
segment leak. Partly, for this reason, a variety of complex salvage techniques
have been described to save the graft in such circumstances. We report a case of
a series of extreme complications related to a leak from the duodenal segment
after a simultaneous pancreas and kidney transplant. These included infected
thrombosis of the inferior vena cava associated with a graft venous thrombosis
and a retroperitoneal fistula. The patient retained graft function with insulin
independence and repeatedly declined graft pancreatectomy against the advice of
the transplant team. Conservative treatment with percutaneous drainage,
antibiotics, and anticoagulation was eventually successful. This outcome is
unique in our experience and may be instructive to teams caring for pancreas
transplant recipients.
PMID- 27500245
TI - Organ Donation Among Tiers of Health Workers: Expanding Resources to Optimize
Organ Availability in a Developing Country.
AB - The global increase in end organ failure but disproportional shortage of organ
donation calls for attention. Expanding the organ pool by assessing and improving
health workers' attitude at all levels of care may be a worthwhile initiative.
METHODS: A questionnaire-based cross sectional study involving tertiary,
secondary, and primary health institutions in Southwestern Nigeria was conducted.
RESULTS: Age range was 18 to 62 (36.7 +/- 9.2) years. Only 13.5%, 11.7%, and
11.2% from primary, secondary, and tertiary health centers, respectively, would
definitely donate despite high level of awareness (>90%) at each level of care.
Participants from primary health care are of low income (P < 0.05), and this
cohort is less likely to be aware of organ donation (P < 0.05). At each level of
care, permission by religion to donate organs influenced positive attitudes
(willingness to donate, readiness to counsel families of potential donors, and
signing of organ donation cards) toward organ donation. Good knowledge of organ
donation only significantly influenced readiness to counsel donors (P < 0.05) and
not willingness to donate (P > 0.05). At each level of health care, young health
care workers (P < 0.05) and women (P > 0.05) would be willing to donate, whereas
men show positive attitude in signing of organ donor cards (P < 0.05) and
counseling of families of potential donors (P > 0.05). CONCLUSIONS: Knowledge and
willingness to donate organs among health care levels were not different.
Considering the potential advantage of community placement of other tiers of
health care (primary and secondary) in Nigeria, integrating them would be
strategically beneficial to organ donation.
PMID- 27500246
TI - Renal Transplantation From a Living Donor With a Horseshoe Kidney.
PMID- 27500247
TI - Identifying Effective Enzyme Activity Targets for Recombinant Class I and Class
II Collagenase for Successful Human Islet Isolation.
AB - Isolation following a good manufacturing practice-compliant, human islet product
requires development of a robust islet isolation procedure where effective limits
of key reagents are known. The enzymes used for islet isolation are critical but
little is known about the doses of class I and class II collagenase required for
successful islet isolation. METHODS: We used a factorial approach to evaluate the
effect of high and low target activities of recombinant class I (rC1) and class
II (rC2) collagenase on human islet yield. Consequently, 4 different enzyme
formulations with divergent C1:C2 collagenase mass ratios were assessed, each
supplemented with the same dose of neutral protease. Both split pancreas and
whole pancreas models were used to test enzyme targets (n = 20). Islet yield/g
pancreas was compared with historical enzymes (n = 42). RESULTS: Varying the
Wunsch (rC2) and collagen degradation activity (CDA, rC1) target dose, and
consequently the C1:C2 mass ratio, had no significant effect on tissue digestion.
Digestions using higher doses of Wunsch and CDA resulted in comparable islet
yields to those obtained with 60% and 50% of those activities, respectively.
Factorial analysis revealed no significant main effect of Wunsch activity or CDA
for any parameter measured. Aggregate results from 4 different collagenase
formulations gave 44% higher islet yield (>5000 islet equivalents/g) in the
body/tail of the pancreas (n = 12) when compared with those from the same segment
using a standard natural collagenase/protease mixture (n = 6). Additionally,
islet yields greater than 5000 islet equivalents/g pancreas were also obtained in
whole human pancreas. CONCLUSIONS: A broader C1:C2 ratio can be used for human
islet isolation than has been used in the past. Recombinant collagenase is an
effective replacement for the natural enzyme and we have determined that high
islet yield can be obtained even with low doses of rC1:rC2, which is beneficial
for the survival of islets.
PMID- 27500248
TI - Successful Kidney and Lung Transplantation From a Deceased Donor With Blunt
Abdominal Trauma and Intestinal Perforation.
AB - The number of organ donors is limited by many contraindications for donation and
poor quality of potential organ donors. Abdominal infection is a generally
accepted contraindication for donation of abdominal organs. We present a 43-year
old man with lethal brain injury, blunt abdominal trauma, and intestinal
perforation. After withdrawal of life-sustaining treatment and circulatory
arrest, a minilaparotomy confirmed abdominal contamination with intestinal
content. After closure of the abdomen, organs were preserved with in situ
preservation with an aortic cannula inserted via the femoral artery. Thereafter,
the kidneys were procured via bilateral lumbotomy to reduce the risk of direct
bacterial contamination; lungs were retrieved following a standard practice.
There was no bacterial or fungal growth in the machine preservation fluid of both
kidneys. All organs were successfully transplanted, without postoperative
infection, and functioned well after 6 months. We hereby show that direct
contamination of organs can be avoided with the use of in situ preservation and
retroperitoneal procurement. Intestinal perforation is not an absolute
contraindication for donation, although the risk of bacterial or fungal
transmission has to be evaluated per case.
PMID- 27500249
TI - Indicators to Identify Trafficking in Human Beings for the Purpose of Organ
Removal.
AB - This article presents indicators to support transplant professionals, judicial
and law enforcement authorities and victim support workers with the
identification of trafficking in persons for the purpose of organ removal. It
outlines the legal and illegal service providers that facilitate trafficking in
human beings for the purpose of organ removal and guides the reader through the
following criminal process: recruitment, transport, entrance, documents, housing,
transplant, aftercare, and finance. Identification of illegal transplant
activities by transplant professionals can support police and judiciary with the
investigation, disruption, and prosecuting of trafficking networks.
PMID- 27500250
TI - Stimulating and Enhancing Partnerships Between Transplant Professionals and Law
Enforcement: Recommendations.
AB - To help combat trafficking in human beings for organ removal (THBOR), transplant
professionals need to do more than carry out careful, multidisciplinary screening
of potential living donors; they also need to communicate and collaborate with
law enforcement professionals. This will involve transplant professionals
educating investigators and prosecutors about transplant practices and in turn
learning about THBOR and how it is prosecuted. Cases of illegal organ
transplantation need to be detected at different levels. First, the victims of
the crime itself need to be identified, especially when they present themselves
for screening. Physicians have a collective responsibility to prevent
exploitation of people, including THBOR victims. The second level involves the
more difficult matter of making reports that involve transplant tourists who have
returned home after receipt of an organ and need follow-up care. Besides
counseling patients prospectively about the legal as well as medical risks in
receiving a vended organ in a foreign transplant center, physicians treating such
patients could have an obligation to report what has happened, if the government
has established a mechanism that either allows reporting THBOR that does not
include the identity of the patient or that treats patients as victims provided
they cooperate in investigation and prosecution of the persons responsible for
obtaining or implanting the organs. The third level of cooperation involves
transplant professionals who participate in THBOR. Professional societies need to
undertake programs to make physicians and nurses aware that their responsibility
to protect their professions' reputation includes identifying members of their
professions who depart from professional ethics. Doing so allows the local
professional societies and state boards to discipline such violators. All 3 of
these functions would be facilitated by the creation by an international body
such as World Health Organization of a registry of patients who travel
internationally to receive a legitimate organ transplant.
PMID- 27500251
TI - Establishing Trafficking in Human Beings for the Purpose of Organ Removal and
Improving Cross-Border Collaboration in Criminal Cases: Recommendations.
AB - In this short summary report on the legal definition of trafficking in human
beings for the purpose of organ removal and improving cross-border collaboration
in criminal cases, challenges, and recommendations in the areas of defining the
crime, criminal investigation and prosecution, and cross-border cooperation are
made. These are the outcomes of a working group discussion during the writers'
conference of the HOTT project, a European Union-funded project against
trafficking in human beings for the purpose of organ removal.
PMID- 27500252
TI - Protection of Human Beings Trafficked for the Purpose of Organ Removal:
Recommendations.
AB - This report presents a comprehensive set of recommendations for protection of
human beings who are trafficked for the purpose of organ removal or are targeted
for such trafficking. Developed by an interdisciplinary group of international
experts under the auspices of the project Trafficking in Human Beings for the
Purpose of Organ Removal (also known as the HOTT project), these recommendations
are grounded in the view that an individual who parts with an organ for money
within an illegal scheme is ipso facto a victim and that the crime of trafficking
in human beings for the purpose of organ removal (THBOR) intersects with the
crime of trafficking in organs. Consequently, the protection of victims should be
a priority for all actors involved in antitrafficking activities: those combating
organ-related crimes, such as health organizations and survivor support services,
and those combating trafficking in human beings, such as the criminal justice
sectors. Taking into account the special characteristics of THBOR, the authors
identify 5 key stakeholders in the protection of human beings trafficked for
organ removal or targeted for such trafficking: states, law enforcement agencies
and judiciary, nongovernmental organizations working in the areas of human rights
and antitrafficking, transplant centers and health professionals involved in
transplant medicine, and oversight bodies. For each stakeholder, the authors
identify key areas of concern and concrete measures to identify and protect the
victims of THBOR. The aim of the recommendations is to contribute to the
development of a nonlegislative response to THBOR, to promote the exchange of
knowledge and best practices in the area of victim protection, and to facilitate
the development of a policy-driven action plan for the protection of THBOR
victims in the European Union and worldwide.
PMID- 27500253
TI - Trafficking in Human Beings for the Purpose of Organ Removal and the Ethical and
Legal Obligations of Healthcare Providers.
AB - Physicians and other health care professionals seem well placed to play a role in
the monitoring and, perhaps, in the curtailment of the trafficking in human
beings for the purpose of organ removal. They serve as important sources of
information for patients and may have access to information that can be used to
gain a greater understanding of organ trafficking networks. However, well
established legal and ethical obligations owed to their patients can create
challenging policy tensions that can make it difficult to implement policy action
at the level of the physician/patient. In this article, we explore the role-and
legal and ethical obligations-of physicians at 3 key stages of patient
interaction: the information phase, the pretransplant phase, and the
posttransplant phase. Although policy challenges remain, physicians can still
play a vital role by, for example, providing patients with a frank disclosure of
the relevant risks and harms associated with the illegal organ trade and an
honest account of the physician's own moral objections. They can also report
colleagues involved in the illegal trade to an appropriate regulatory authority.
Existing legal and ethical obligations likely prohibit physicians from reporting
patients who have received an illegal organ. However, given the potential
benefits that may accrue from the collection of more information about the
illegal transactions, this is an area where legal reform should be considered.
PMID- 27500254
TI - The Hague Recommendations: Improving Nonlegislative Responses to Trafficking in
Human Beings for the Purpose of Organ Removal.
AB - Over the years, the trade in human organs has become an object of international
concern. Since the 1980s, antiorgan trade initiatives have mainly involved the
strengthening of legislative responses. Little attention however is given to
nonlegislative responses by law enforcement authorities. The HOTT project is a
European Union-funded research project titled "trafficking in human beings for
the purpose of organ removal." Its objectives are to increase knowledge, raise
awareness, and improve the nonlegislative response to the crime. Its consortium
organized a "Writers' Conference" in The Hague, The Netherlands at Europol's
Headquarters where a group of 40 experts, consisting of transplant professionals,
law enforcement officials, and policy makers, formulated recommendations to
improve nonlegislative responses. These recommendations, presented hereafter,
address the ethical and legal obligations of health care providers, the
protection of persons trafficked for the purpose of organ removal, strengthening
cross-border collaboration in criminal cases, and stimulating partnerships
between transplant professionals and law enforcement. These recommendations offer
ways in which transplant professionals can contribute to improving the
nonlegislative response to trafficking in human beings for the purpose of organ
removal.
PMID- 27500255
TI - Early and Sustained Reduction in Donor-Specific Antibodies in Desensitized Living
Donor Kidney Transplant Recipients: A 3-Year Prospective Study.
AB - BACKGROUND: Desensitization with IVIG and rituximab allows acceptable graft
survival in sensitized kidney transplant recipients with preexisting donor
specific antibodies (DSAs) and a positive crossmatch. There is little published
data reporting the durability of DSA removal in kidney transplant recipients
treated with IVIG and rituximab. METHODS: We conducted a 3-year prospective DSA
monitoring study in living donor kidney recipients with preexisting DSA to assess
the durability of DSA removal after a perioperative protocol of IVIG and
rituximab. All recipients had flow crossmatch titers less than 1:32. Data were
analyzed using linear mixed effects models and Kaplan-Meier survival methods.
RESULTS: The longitudinal database comprised 210 mean fluorescence intensity
(MFI) determinations. Forty-two DSAs were identified in 29 patients. Pretreatment
MFI averaged 4715 +/- 3962 (range, 947-20 129). At 1 month posttransplant, 18
patients (62%) had a complete response (MFI < 1000) and an additional 9 patients
(31%) had a partial response (MFI reduced but >1000). There was a 46% reduction
(P < 0.001) in DSA MFI at 1 month posttransplant that was sustained throughout
the 3-year follow-up period and was observed for both class I and II DSAs
regardless of pretreatment MFI levels. With a mean posttransplant follow-up of
1048 +/- 574 days, 3-year patient and graft survivals were 95% and 90%. Four
patients (14%) had acute rejection between days 125 and 560. CONCLUSIONS:
Desensitization with IVIG and rituximab results in early and sustained DSA
removal over a 3-year posttransplant period in living donor kidney transplant
recipients with pretransplant DSA and a positive crossmatch, excellent patient
and graft survivals and a low incidence of acute rejection.
PMID- 27500256
TI - A Preliminary Study Into the Significance of Intrarenal Reflux in BK Virus
Nephropathy After Kidney Transplantation.
AB - BACKGROUND: The BK virus typically colonizes the lower urinary tract and is the
causative agent in BK virus nephropathy (BKVN), which can progress to allograft
dysfunction and graft loss. Urinary reflux in kidney allografts is induced by
vesicoureteral reflux or disturbances in intrarenal reflux (IRR), believed to be
associated with BKVN. This study was designed to elucidate the relationship
between BKVN and IRR. METHODS: We examined 30 renal transplant recipients
histologically diagnosed with BKVN using anti-Simian virus 40
immunohistochemistry and 60 clinically matched control recipients. The BKVN
patients were divided into stable (n = 12) and progressive (n = 18) groups
according to allograft kidney function 1 year after diagnosis. Histological
rejection scores according to the pathological classification of rejection in
renal allografts (Banff classification), histological BKVN stages, and
histological polyomavirus load levels (pvl) proposed by the Banff working group
were evaluated. The IRR was quantified by histological reflux scores defined with
retention and reflux of immunostained Tamm-Horsfall protein in renal tubules and
glomeruli. RESULTS: Higher reflux scores were observed in the BKVN group compared
with that in the control group. No differences in clinical parameters were
observed between the BKVN and control groups. Reflux scores and pvl were
significantly higher in the progressive group than in the stable BKVN group with
no significant difference in BK stage observed between groups. Reflux scores were
found to be significantly correlated with pvl. CONCLUSIONS: Our preliminary study
suggested that IRR might be a predisposing and prognostic factor in BKVN.
PMID- 27500257
TI - mTOR Inhibition: Reduced Insulin Secretion and Sensitivity in a Rat Model of
Metabolic Syndrome.
AB - BACKGROUND: Sirolimus (SRL) has been associated with new-onset diabetes mellitus
after transplantation. The aim was to determine the effect of SRL on development
of insulin resistance and beta -cell toxicity. METHODS: Lean Zucker rat (LZR) and
obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5,
or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test
(IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, beta-cell
proliferation, and apoptosis were analyzed at 12 days. Islets were isolated to
analyze insulin content, insulin secretion, and gene expression. RESULTS: After
12 days, SRL treatment only impaired IPGTT in a dose-dependent manner in OZR.
Treatment prolongation induced increase of area under the curve of IPGTT in LZR
and OZR; however, in contrast to OZR, LZR normalized glucose levels after 2
hours. The SRL reduced pancreas weight and islet proliferation in LZR and OZR as
well as insulin content. Insulin secretion was only affected in OZR. Islets from
OZR + SRL rats presented a downregulation of Neurod1, Pax4, and Ins2 gene. Genes
related with insulin secretion remained unchanged or upregulated. CONCLUSIONS: In
conditions that require adaptive beta -cell proliferation, SRL might reveal
harmful effects by blocking beta -cell proliferation, insulin production and
secretion. These effects disappeared when removing the therapy.
PMID- 27500258
TI - Lowered Immune Cell Function in Liver Recipients Recovered From Posttransplant
Lymphoproliferative Disease Who Developed Graft Tolerance.
AB - Tolerance after treatment and recovery from posttransplant lymphoproliferative
disease (PTLD) have been described but little is known about the immunology. The
objective of this study is to evaluate the immunity of pediatric recipients who
recovered from PTLD. MATERIALS AND METHODS: Pediatric recipients who recovered
from PTLD after liver transplant and twice the number of recipients who never had
PTLD were recruited. Their immune statuses were measured by ImmuKnow (measurement
of adenosine 5-triphospate level produced CD4+ T helper cells), and the results
were divided into 3 groups, "low" (<=225 ng/mL), "moderate" (226 to 524 ng/mL),
and "high" (>=525 ng/mL). The results of both groups were compared and analyzed.
RESULTS: Nine PTLD recipients and 20 non-PTLD recipients were recruited. There
were no significant differences in terms of sex and age between the 2 groups. The
majority of PTLD recipients (88.9%) had "low" immune status responses, and none
of them had "high" responses. For non-PTLD recipients, more than half (55%) had
"moderate" immune status responses. The median value of adenosine 5-triphospate
levels was significantly lower in the PTLD group (119 ng/mL vs 380.5 ng/mL P =
0.014), and their trough immunosuppressant level was also lower (3.8 MUg/L vs 7.7
MUg/L; P = 0.004). None of the patients in either group had abnormal liver
enzymes (aspartate aminotransferase/alanine aminotransferase) to suggest graft
rejection. CONCLUSIONS: Patients who recovered from PTLD have a lower CD4 T-cell
activity compared with those who have not suffered from PTLD. Under careful
monitoring, their immunosuppressant levels can be kept at low levels to prevent
recurrence of PTLD.
PMID- 27500259
TI - Deep Vein Thrombosis and Pulmonary Embolism in Liver Transplant Patients: Risks
and Prevention.
AB - Deep vein thrombosis (DVT) and pulmonary embolism (PE) are surgical complications
estimated to occur in 5% to 10% of patients. There are limited data regarding
DVT/PE in the early postoperative period in liver transplant patients. The aim of
this study is to determine risk factors that influence the incidence of DVT/PE
and the effectiveness of prophylaxis. METHODS: We reviewed the records of 999
patients who underwent initial liver transplant between January 2000 and June
2012 at Henry Ford Hospital. In 2011, a standardized prophylactic regimen using
subcutaneous (SQ) heparin was initiated. All patients that developed either
upper/lower extremity DVT or PE within the first 30 days of transplant formed the
cohort of this study. RESULTS: On multivariate analysis, only peripherally
inserted central catheter (PICC) placement and SQ heparin were associated with
DVT/PE. In patients receiving heparin, 3 (1.0%) had DVT/PE versus 25 (3.5%) who
did not receive heparin (P = 0.03). Sixteen (6.9%) patients that had a PICC
developed DVT/PE compared with 12 (1.6%) patients without a PICC (P < 0.001). In
the heparin group, DVT/PE with PICC was reduced to 3 (3.0%) versus 13 (9.9%) in
those with a PICC and did not receive heparin (P = 0.03). Mean time from
transplant to DVT/PE diagnosis was 12.3 days. Length of hospitalization was
significantly longer in patients who developed DVT/PE (18.5 vs 10.0 days, P <
0.001). CONCLUSIONS: In this study, we demonstrated that PICC placement
significantly increases the likelihood of DVT/PE in liver transplant recipients.
Prophylactic SQ heparin effectively reduced DVT/PE events in this patient
population.
PMID- 27500260
TI - Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus
Immunosuppression in Renal Allograft Recipients.
AB - Calcineurin inhibitor-associated nephrotoxicity and other adverse events have
prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney
transplant recipients. METHODS: This open-label, randomized, multinational study
evaluated the effect of planned transition from tacrolimus to sirolimus on kidney
function in renal allograft recipients. Patients received tacrolimus-based
immunosuppression and then were randomized 3 to 5 months posttransplantation to
transition to sirolimus or continue tacrolimus. The primary end point was
percentage of patients with 5 mL/min per 1.73 m(2) or greater improvement in
estimated glomerular filtration rate from randomization to month 24. RESULTS: The
on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No
between-group difference was noted in percentage of patients with 5 mL/min per
1.73 m(2) or greater estimated glomerular filtration rate improvement (sirolimus,
34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates
of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment
discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower
rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). CONCLUSIONS:
Our findings suggest that renal function improvement at 24 months is similar for
patients with early conversion to sirolimus after kidney transplantation versus
those remaining on tacrolimus.
PMID- 27500261
TI - Successful Management of Calciphylaxis in a Kidney Transplant Patient: Case
Report.
AB - Calciphylaxis is a rare and often fatal condition mostly associated with end
stage renal disease. The pathophysiology remains elusive and treatment options
are scarce. We present a rare case of severe calciphylaxis after kidney
transplantation in a patient with persistent hyperparathyroidism. CASE
DESCRIPTION: A 78-year-old man with a history of end-stage renal disease
developed edema and ulcerations on both lower limbs 14 months after kidney
transplantation while receiving an mammalian target of rapamycin inhibitor to
manage polyoma virus-associated nephropathy. Skin biopsies taken from the
ulcerations confirmed calciphylaxis. A multimodal treatment regimen combining
medical (calcium-free phosphate binders, cinacalcet, paricalcitol, sodium
thiosulfate, antibiotic treatment) and surgical treatments (debridement and
autologous skin transplantation) ultimately resulted in successful wound healing.
DISCUSSION: We describe a case of severe calciphylaxis in a nonuremic patient
after kidney transplantation. Rapid diagnosis by skin biopsy and an aggressive
multimodal therapy regimen followed by long-term oral sodium thiosulfate
treatment were crucial factors for a favorable outcome.
PMID- 27500262
TI - Well, I Wouldn't be Any Worse Off, Would I, Than I am Now? A Qualitative Study of
Decision-Making, Hopes, and Realities of Adults With Type 1 Diabetes Undergoing
Islet Cell Transplantation.
AB - BACKGROUND: For selected individuals with type 1 diabetes, pancreatic islet
transplantation (IT) prevents recurrent severe hypoglycemia and optimizes
glycemia, although ongoing systemic immunosuppression is needed. Our aim was to
explore candidates and recipients' expectations of transplantation, their
experience of being on the waiting list, and (for recipients) the procedure and
life posttransplant. METHODS: Cross-sectional qualitative research design using
semistructured interviews with 16 adults (8 pretransplant, 8 posttransplant; from
4 UK centers (n = 13) and 1 Canadian center (n = 3)). Interviews were audio
recorded, transcribed, and underwent inductive thematic analysis. RESULTS:
Interviewees were aged (mean +/- SD) 52 +/- 10 years (range, 30-64); duration of
diabetes, 36 +/- 9 years (range, 21-56); 12 (75%) were women. Narrative accounts
centered on expectations, hopes, and realities; decision-making; waiting and
uncertainty; the procedure, hospital stay, and follow-up. Expected benefits
included fewer severe hypoglycemic episodes, reduced need for insulin, preventing
onset/progression of complications and improved psychological well-being. These
were realized for most, at least in the short term. Most interviewees described
well-informed, shared decision-making with clinicians and family, and managing
their expectations. Although life "on the list" could be stressful, and
immunosuppressant side effects were severe, interviewees reported "no regrets."
Posttransplant, interviewees experienced increased confidence, through freedom
from hypoglycemia and regained glycemic control, which tempered any
disappointment about continued reliance on insulin. Most viewed their transplant
as a success, though several reflected upon setbacks and hidden hopes for
becoming "insulin-free." CONCLUSIONS: Independently undertaken interviews
demonstrated realistic and balanced expectations of IT and indicate how to
optimize the process and support for future IT candidates.
PMID- 27500264
TI - Outcomes of Living Donor Liver Transplantation Alone for Patients on Maintenance
Renal Replacement Therapy in Japan: Results of a Nationwide Survey.
AB - BACKGROUND: Because simultaneous liver and kidney transplantation has been
limited as a standard practice because of a severe shortage of deceased donors in
Japan, living donor (LD) liver transplantation alone (LTA) is indicated in most
recipients with maintenance renal replacement therapy (MRRT). METHODS: A
retrospective nationwide survey of LD LTA was performed for liver transplant
patients on MRRT. The characteristics of donors and recipients, postoperative
complications, survival rate, and causes of death were analyzed. RESULTS: In the
adult cases (n = 28), the overall survival rate at 1 year and 5 years were 66.1%
and 57.3%, respectively. When compared with those adults without MRRT (n = 237),
it was significantly worse. In the 7 pediatric cases, the overall survival rate
at 1 and 5 years were both 83.3%. Three adult recipients died of nonaneurysm
cerebral hemorrhage after 1 year and 1 adult recipient died of acute heart
failure after 7 months. In adult recipients with MRRT, graft weight versus
standard liver volume, and duration and blood loss in LTA surgery were associated
with poor outcomes after LD LTA. Multivariate analysis revealed that MRRT was
highest hazard ratio on patient survival after LD LTA. CONCLUSIONS: Early post-LD
LTA mortality was higher in patients with MRRT than in those without MRRT with
characteristic causes. Smaller grafts for size and a complicated surgery were
associated with poor outcome after LD LTA. Thus, LD LTA in adult patients on MRRT
should be carefully treated with meticulous postoperative management and follow
up.
PMID- 27500263
TI - Kinetics of Alloantigen-Specific Regulatory CD4 T Cell Development and Tissue
Distribution After Donor-Specific Transfusion and Costimulatory Blockade.
AB - BACKGROUND: The influence of donor-side regulation toward recipient antigens on
graft outcome is poorly understood. METHODS: Because this influence might be due
in part to the accumulation of tissue-resident memory T cells in the donor organ,
we used a standard murine tolerization model (donor-specific transfusion plus
CD40L blockade) to determine the kinetics of development and peripheralization of
allospecific regulatory T cell in lymphoid tissues and liver, a secondary
lymphoid organ used in transplantation. RESULTS: We found that donor-specific
transfusion and CD40L blockade leads to a progressive and sustained T regulatory
allospecific response. The cytokines IL10, TGFbeta, and IL35 all contributed to
the regulatory phenomenon as determined by trans vivo delayed hypersensitivity
assay. Unexpectedly, an early and transient self-specific regulatory response was
found as well. Using double reporter mice (forkhead box p 3 [Foxp3]-yellow
fluorescent protein, Epstein-Barr virus-induced gene 3 [Ebi3]-TdTomRed), we found
an increase in Foxp3+CD25+ regulatory T (Treg) cells paralleling the regulatory
response. The Ebi3+ CD4 T cells (IL35-producing) were mainly classic Treg cells
(Foxp3+CD25+), whereas TGFbeta+ CD4 T cells are mostly Foxp3-negative, suggesting
2 different CD4 Treg cell subsets. Liver-resident TGFbeta+ CD4 T cells appeared
more rapidly than Ebi3-producing T cells, whereas at later timepoints, the Ebi3
response predominated both in lymphoid tissues and liver. CONCLUSIONS: The timing
of appearance of donor organ resident Treg cell subsets should be considered in
experiments testing the role of bidirectional regulation in transplant tolerance.
PMID- 27500265
TI - Kidney Transplant Outcomes After Primary, Repeat and Kidney After Nonrenal Solid
Organ Transplantation: A Single-Center Experience.
AB - BACKGROUND: Improvements in renal allograft outcomes have permitted kidney
transplantation after prior kidney allograft failure as well as after nonrenal
solid organ transplantation. This study compares renal allograft outcomes in the
3 groups, that is, primary, repeat, and kidney after nonrenal solid organ
transplantation, where transplant group was coded as a time-dependent variable.
METHODS: We retrospectively reviewed registry data for kidney transplant
recipients at University of Pittsburgh Medical Center from January 2000 to
December 2011. We compared overall graft survival between the 3 groups using Cox
regression modeling. We calculated 1-, 3-, and 5-year graft survival and half
lives for each group where feasible. RESULTS: The study cohort (N = 2014)
consisted of group A (primary kidney transplant, n = 1578, with 7923.2 years of
follow-up time), group B (repeat kidney transplant, n = 314, with 1566.7 years of
follow-up time) and group C (kidney post-nonrenal solid organ transplant, n =
176, with 844.8 years of follow-up time). Of the 1578 patients in the primary
kidney transplant group, 74 later received a repeat transplant and thus also have
follow-up counted in the repeat kidney transplant group. The median follow-up was
56, 53, and 55 months, respectively. The 5-year actuarial and death-censored
graft survival was 68.69%, 68.79%, and 66.48% and 65.53%, 67.68%, and 62.92%,
respectively (P = 0.70). There was no difference in overall graft survival in the
Cox-adjusted analysis (group B: odds ratio, 1.02; 95% confidence interval, 0.84
1.26; P = 0.79; group C: odds ratio, 0.96; 95% confidence interval, 0.75-1.23; P
= 0.76). CONCLUSIONS: The adjusted kidney graft survivals in the 3 groups were
similar.
PMID- 27500266
TI - Results of the TOP Study: Prospectively Randomized Multicenter Trial of an Ex
Vivo Tacrolimus Rinse Before Transplantation in EDC Livers.
AB - BACKGROUND: Organ shortage results in the transplantation of extended donor
criteria (EDC) livers which is associated with increased ischemia-reperfusion
injury (IRI). Experimental studies indicate that an organ rinse with the
calcineurin inhibitor tacrolimus before implantation protects against IRI. The
tacrolimus organ perfusion study was initiated to examine the effects of ex vivo
tacrolimus perfusion on IRI in transplantation of EDC livers. METHODS: A
prospective randomized multicenter trial comparing ex vivo perfusion of marginal
liver grafts (>=2 EDC according to Eurotransplant manual) with tacrolimus (20
ng/mL) or histidine-tryptophane-ketoglutarate solution (control) was carried out
at 5 German liver transplant centers (Munich Ludwig-Maximilians University,
Berlin, Heidelberg, Mainz, Regensburg) between October 2011 and July 2013.
Primary endpoint was the maximum alanine transaminase (ALT) level within 48 hours
after transplantation. Secondary endpoints were aspartate transaminase (AST),
prothrombine ratio, and graft-patient survival within an observation period of 1
week. After an interim analysis, the study was terminated by the scientific
committee after the treatment of 24 patients (tacrolimus n = 11, Control n = 13).
RESULTS: Tacrolimus rinse did not reduce postoperative ALT peaks compared with
control (P = 0.207; tacrolimus: median, 812; range, 362-3403 vs control: median,
652; range, 147-2034). Moreover, ALT (P = 0.100), prothrombine ratio (P = 0.553),
and bilirubin (P = 0.815) did not differ between the groups. AST was higher in
patients treated with tacrolimus (P = 0.011). Survival was comparable in both
groups (P > 0.05). CONCLUSIONS: Contrary to experimental findings, tacrolimus
rinse failed to improve the primary endpoint of the study (ALT). Because 1
secondary endpoint (AST) was even higher in the intervention group, the study was
terminated prematurely. Thus, tacrolimus rinse cannot be recommended in
transplantation of EDC livers.
PMID- 27500267
TI - Characterizing the Mechanistic Pathways of the Instant Blood-Mediated
Inflammatory Reaction in Xenogeneic Neonatal Islet Cell Transplantation.
AB - INTRODUCTION: The instant blood-mediated inflammatory reaction (IBMIR) causes
major loss of islets after transplantation and consequently represents the
initial barrier to survival of porcine neonatal islet cell clusters (NICC) after
xenotransplantation. METHODS: This study used novel assays designed to
characterize the various immunologic components responsible for xenogeneic IBMIR
to identify initiators and investigate processes of IBMIR-associated coagulation,
complement activation and neutrophil infiltration. The IBMIR was induced in vitro
by exposing NICC to platelet-poor or platelet-rich human plasma or isolated
neutrophils. RESULTS: We found that xenogeneic IBMIR was characterized by rapid,
platelet-independent thrombin generation, with addition of platelets both
accelerating and exacerbating this response. Platelet-independent complement
activation was observed as early as 30 minutes after NICC exposure to plasma.
However, membrane attack complex formation was not observed in NICC
histopathology sections until after 60 minutes. We demonstrated for the first
time that NICC-mediated complement activation was necessary for neutrophil
activation in the xenogeneic IBMIR setting. Finally, using the Seahorse
extracellular flux analyzer, we identified substantial loss of islet function (up
to 40%) after IBMIR with surviving NICC showing evidence of mitochondrial damage.
CONCLUSIONS: This study used novel assays to describe multiple key pathways by
which xenogeneic IBMIR causes islet destruction, allowing further refinement of
future interventions aimed at resolving the issue of IBMIR in
xenotransplantation.
PMID- 27500268
TI - Detecting Renal Allograft Inflammation Using Quantitative Urine Metabolomics and
CXCL10.
AB - BACKGROUND: The goal of this study was to characterize urinary metabolomics for
the noninvasive detection of cellular inflammation and to determine if adding
urinary chemokine ligand 10 (CXCL10) improves the overall diagnostic
discrimination. METHODS: Urines (n = 137) were obtained before biopsy in 113
patients with no (n = 66), mild (borderline or subclinical; n = 58), or severe
(clinical; n = 13) rejection from a prospective cohort of adult renal transplant
patients (n = 113). Targeted, quantitative metabolomics was performed with direct
flow injection tandem mass spectrometry using multiple reaction monitoring (ABI
4000 Q-Trap). Urine CXCL10 was measured by enzyme-linked immunosorbent assay. A
projection on latent structures discriminant analysis was performed and validated
using leave-one-out cross-validation, and an optimal 2-component model developed.
Chemokine ligand 10 area under the curve (AUC) was determined and net
reclassification index and integrated discrimination index analyses were
performed. RESULTS: PLS2 demonstrated that urinary metabolites moderately
discriminated the 3 groups (Cohen kappa, 0.601; 95% confidence interval [95% CI],
0.46-0.74; P < 0.001). Using binary classifiers, urinary metabolites and CXCL10
demonstrated an AUC of 0.81 (95% CI, 0.74-0.88) and 0.76 (95% CI, 0.68-0.84),
respectively, and a combined AUC of 0.84 (95% CI, 0.78-0.91) for detecting
alloimmune inflammation that was improved by net reclassification index and
integrated discrimination index analyses. Urinary CXCL10 was the best univariate
discriminator, followed by acylcarnitines and hexose. CONCLUSIONS: Urinary
metabolomics can noninvasively discriminate noninflamed renal allografts from
those with subclinical and clinical inflammation, and the addition of urine
CXCL10 had a modest but significant effect on overall diagnostic performance.
These data suggest that urinary metabolomics and CXCL10 may be useful for
noninvasive monitoring of alloimmune inflammation in renal transplant patients.
PMID- 27500270
TI - The Effect of Mycophenolate Mofetil on Early Wound Healing in a Rodent Model.
AB - BACKGROUND: Immunosuppressant agents are inevitable for solid organ recipients,
but may have a negative effect on wound healing that is difficult to measure
because of clinical use of a polydrug regime. The evidence on mycophenolate
mofetil (MMF) is scarce and contradictory. This study aims to investigate the
effect of MMF administration on wound healing. METHODS: Ninety-six male Wistar
rats divided into 4 groups underwent anastomotic construction in ileum and colon
at day 0. Three groups received daily oral doses of 20 or 40 mg/kg MMF or saline
(control group) from day 0 until the end of the experiment. Half of each group
was analyzed after 3 days and half after 7 days. Another group started the
medication 3 days after the laparotomy and was analyzed after 7 days, half of
this group received 20 mg/kg and half 40 mg/kg MMF. Wound strength in anastomoses
and in the abdominal wall was measured using bursting pressure, breaking
strength, and histology. Trough levels were measured. RESULTS: Significant
differences in wound strength were seen in ileum tissue after 3 days, which
surprisingly showed a stronger anastomosis in the experimental groups. Bursting
pressure as well as breaking strength was higher in the low-dose and high-dose
MMF group compared with the control group. A negative effect was measured in
abdominal wall tissue for the highest-dose group, which disappeared when the
medication was delayed for 3 days. Histology showed poorer bridging of the
submucosal layer and more polymorphonuclear cell infiltration in the ileum
specimens of the control group compared with the treatment groups. CONCLUSIONS:
As a single agent in a preclinical wound healing model in the rat, MMF has no
negative effect on healing of bowel anastomoses but might have a negative effect
on the healing of abdominal wall.
PMID- 27500269
TI - Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to
Develop a Core Outcome Set for Trials in Kidney Transplantation.
AB - BACKGROUND: Although advances in treatment have dramatically improved short-term
graft survival and acute rejection in kidney transplant recipients, long-term
graft outcomes have not substantially improved. Transplant recipients also have a
considerably increased risk of cancer, cardiovascular disease, diabetes, and
infection, which all contribute to appreciable morbidity and premature mortality.
Many trials in kidney transplantation are short-term, frequently use unvalidated
surrogate endpoints, outcomes of uncertain relevance to patients and clinicians,
and do not consistently measure and report key outcomes like death, graft loss,
graft function, and adverse effects of therapy. This diminishes the value of
trials in supporting treatment decisions that require individual-level multiple
tradeoffs between graft survival and the risk of side effects, adverse events,
and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative
aims to develop a core outcome set for trials in kidney transplantation that is
based on the shared priorities of all stakeholders. METHODS: This will include a
systematic review to identify outcomes reported in randomized trials, a Delphi
survey with an international multistakeholder panel (patients, caregivers,
clinicians, researchers, policy makers, members from industry) to develop a
consensus-based prioritized list of outcome domains and a consensus workshop to
review and finalize the core outcome set for trials in kidney transplantation.
CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a
minimum, in all kidney transplantation trials will improve the transparency,
quality, and relevance of research; to enable kidney transplant recipients and
their clinicians to make better-informed treatment decisions for improved patient
outcomes.
PMID- 27500271
TI - A Proposal for Early Dosing Regimens in Heart Transplant Patients Receiving
Thymoglobulin and Calcineurin Inhibition.
AB - There is currently no consensus regarding the dose or duration of rabbit
antithymocyte globulin (rATG) induction in different types of heart transplant
patients, or the timing and intensity of initial calcineurin inhibitor (CNI)
therapy in rATG-treated individuals. Based on limited data and personal
experience, the authors propose an approach to rATG dosing and initial CNI
administration. Usually rATG is initiated immediately after exclusion of primary
graft failure, although intraoperative initiation may be appropriate in specific
cases. A total rATG dose of 4.5 to 7.5 mg/kg is advisable, tailored within that
range according to immunologic risk and adjusted according to immune monitoring.
Lower doses (eg, 3.0 mg/kg) of rATG can be used in patients at low immunological
risk, or 1.5 to 2.5 mg/kg for patients with infection on mechanical circulatory
support. The timing of CNI introduction is dictated by renal recovery, varying
between day 3 and day 0 after heart transplantation, and the initial target
exposure is influenced by immunological risk and presence of infection. Rabbit
antithymocyte globulin and CNI dosing should not overlap except in high-risk
cases. There is a clear need for more studies to define the optimal dosing
regimens for rATG and early CNI exposure according to risk profile in heart
transplantation.
PMID- 27500272
TI - Successful Kidney Transplantation in Children With a Compromised Inferior Vena
Cava.
AB - BACKGROUND: Children with a compromised inferior vena cava (IVC) were previously
considered unsuitable for kidney transplantation because of the technical
difficulties and the increased risk of graft thrombosis secondary to inadequate
renal venous outflow. METHODS: We conducted a retrospective study of 11
transplants in 9 patients with end-stage renal disease and thrombosed IVCs who
received adult kidney allografts between 2000 and 2015. The mean age at
transplantation was 7.5 +/- 3.5 years. A pretransplant diagnosis of the IVC
thrombosis was made in 7 patients by magnetic resonance imaging and computerized
tomography, whereas there were 2 instances of intraoperative discovery of the IVC
thrombosis. RESULTS: In the early cases, a kidney was placed intraperitoneally at
the right iliac fossa with a venous anastomosis to the patent segment of the
suprarenal IVC. After 2008, however, 6 adult-sized kidneys were subsequently
placed in the left orthotopic position. Venous drainage was attained to the
infrahepatic IVC (n = 3), left native renal vein (n = 2), and ascending lumbar
vein (n = 1). Moreover, a venous bypass was created between the graft and the
splenic vein in 2 children who showed high return pressure after the vessel was
declamped. The mean glomerular filtration rate of the functioning 8 grafts 1 year
posttransplant was 73.4 +/- 20.4 mL/min per 1.73 m(2). Of note, 6 of the grafts
have been functioning well, with a mean follow-up of 66 months. Both 1- and 5
year graft survival were 81.8%. CONCLUSIONS: Transplantation into the left
orthotopic position and the revascularization methods are an effective set of
surgical techniques that could potentially be adopted as safe and reliable
transplant approaches in children with IVC thrombosis.
PMID- 27500273
TI - Alemtuzumab as Antirejection Therapy: T Cell Repopulation and Cytokine
Responsiveness.
AB - BACKGROUND: Alemtuzumab induction therapy in kidney transplant patients results
in T cell depletion followed by slow immune reconstitution of memory T cells with
reduced immune functions. The kinetics and functional characteristics of T cell
reconstitution when alemtuzumab is given during immune activation, ie, as
antirejection therapy, are unknown. METHODS: Patients (n = 12) with
glucocorticoid-resistant or severe vascular kidney transplant rejection were
treated with alemtuzumab. Flow cytometric analysis was performed on whole blood
to measure cell division by the marker Ki-67, and cytokine responsiveness by IL-2
mediated and IL-7-mediated phosphorylation of signal transducer and activator of
transcription 5 of T cells before and during the first year after rejection
therapy. RESULTS: At 1 year after alemtuzumab antirejection therapy, the total T
cell population recovered to baseline level. Repopulation of CD4+ and CD8+ T
cells was associated with increased percentages of Ki-67+ proliferating T cells
(P < 0.05). In addition, both populations showed a phenotypic shift toward
relatively more memory T cells (P < 0.01). At the functional level, IL-7
reactivity of CD4+ memory T cells was diminished, reflected by a decreased
capacity to phosphorylate signal transducer and activator of transcription 5
during the first 6 months after alemtuzumab treatment (P < 0.05), whereas
reactivity to IL-2 was preserved. CD8+ T cells were affected in terms of both IL
2 and IL-7 responses (both P < 0.05). After reconstitution, relatively more
regulatory T cells were present, and a relatively high proportion of Ki-67+ T
cells was observed. CONCLUSIONS: Preliminary data from this small series suggest
that alemtuzumab antirejection therapy induces homeostatic proliferation of
memory and regulatory T cells with diminished responsiveness to the homeostatic
cytokine IL-7. IL-2 responsiveness was affected in repopulated CD8+ T cells.
PMID- 27500274
TI - Highly sensitive sequencing reveals dynamic modifications and activities of small
RNAs in mouse oocytes and early embryos.
AB - Small RNAs play important roles in early embryonic development. However, their
expression dynamics and modifications are poorly understood because of the
scarcity of RNA that is obtainable for sequencing analysis. Using an improved
deep sequencing method that requires as little as 10 ng of total RNA or 50
oocytes, we profile small RNAs in mouse oocytes and early embryos. We find that
microRNA (miRNA) expression starts soon after fertilization, and the mature
miRNAs carried into the zygote by sperm during fertilization are relatively rare
compared to the oocyte miRNAs. Intriguingly, the zygotic miRNAs display a marked
increase in 3' mono- and oligoadenylation in one- to two-cell embryos, which may
protect the miRNAs from the massive degradation taking place during that time.
Moreover, bioinformatics analyses show that the function of miRNA is suppressed
from the oocyte to the two-cell stage and appears to be reactivated after the two
cell stage to regulate genes important in embryonic development. Our study thus
provides a highly sensitive profiling method and valuable data sets for further
examination of small RNAs in early embryos.
PMID- 27500275
TI - Spontaneous Preterm Delivery, Particularly with Reduced Fetal Growth, is
Associated with DNA Hypomethylation of Tumor Related Genes.
AB - BACKGROUND: Preterm delivery and sub-optimal fetal growth are associated with
each other and affect both mother and infant. Our aim was to determine (i)
whether there are detectable differences in DNA methylation between early and
late gestation and (ii) whether changes in DNA methylation from entry are
associated with spontaneous preterm delivery with and without reduced fetal
growth. METHODS: We conducted a case-control study nested within a large
prospective cohort. Gene specific methylation was measured by Methyl-Profiler PCR
Array in a Human Breast Cancer Signature Panel of 24 genes from maternal
peripheral leukocytes genomic DNA at entry and 3rd trimester (sampled at 16 and
30 weeks of gestation, respectively). Clonal bisulfite DNA sequencing was
performed to confirm the changes in selected genes (CYP1B1, GADD45A and CXCL12).
Multivariable analysis was used for data analysis. RESULTS: There was
significantly decrease in DNA methylation in 15 of 24 genes during the 3rd
trimester in cases of spontaneous preterm delivery (n=23) as compared to the
controls (n=19) (p<0.05-p<0.01 for each gene). Similar results were observed by
bisulfite sequencing for 3 genes. The change in DNA methylation between late and
early gestation was significantly different in cases (overall decrease in
methylation was -4.0 +/- 1.5%) compared to the controls (overall increase in
methylation was 12.6 +/- 2.19%, p<0.0001). A graded pattern of DNA methylation
was observed in 15 genes. Cases who delivered preterm with reduced fetal growth
had the lowest level of methylation, cases delivering preterm without reduced
fetal growth were next and term controls were highest in methylation (p for trend
<0.05 to p<0.01 for each gene). Cases of preterm delivery also had significantly
lower dietary choline intake. CONCLUSIONS: These data suggest that epigenetic
modification is associated with an increased risk of spontaneous preterm
delivery, spontaneous preterm delivery with reduced fetal growth in particular.
PMID- 27500276
TI - Number of Primary Care Visits Associated with Screening for Cervical Dysplasia
among Women with HIV Infection in Harris County, Texas, United States of America.
AB - Studies indicate that women with HIV infection in the United States are
inadequately screened for cervical dysplasia. However, few of these studies have
included women in the southern United States, where HIV incidence is now
concentrated. We performed a retrospective chart review of women with HIV
infection in two HIV clinics in a large southern metropolitan area. To describe
screening rates among women in care, only women with >=2 primary care clinic
visits during 2007 were included. We used log-binomial regression to estimate
prevalence ratios and 95% confidence intervals of screening and to identify
demographic, behavioral, and care-related factors associated with screening. Only
52% (258/498) of women in our study were screened during the year; only 29%
(8/28) of women with <=50 CD4 cells/mm3. Factors associated with increased
screening in unadjusted analyses included increased number of primary care visits
(p<0.001), higher CD4 cell count (p<0.001), younger age (p=0.006) and Hispanic
compared to non-Hispanic ethnicity (p<0.001). In adjusted analyses, women with
>=4 primary care visits were 21% more likely to be screened than women with <4
visits (adjusted prevalence ratio = 1.21; 95% confidence interval: 1.02-1.44).
Women with CD4 cell counts <200 cells/mm3 were less likely to be screened than
women with CD4 counts >=350 cells/mm3 (adjusted prevalence ratio: 0.77; 95%
confidence interval: 0.59- 1.00). Rates of screening for cervical dysplasia were
lower than those seen in similar care settings in other geographic areas in the
United States. The number of HIV primary care visits, which has been associated
with retention in care, was associated with screening prevalence. Interventions
designed to improve retention in care may improve screening rates for cervical
dysplasia as well.
PMID- 27500277
TI - Tuning the selectivity and sensitivity of an OmpG nanopore sensor by adjusting
ligand tether length.
AB - We have previously shown that a biotin ligand tethered to the rim of an OmpG
nanopore can be used to detect biotin-binding proteins. Here, we investigate the
effect of the length of the polyethylene glycol tether on the nanopore's
sensitivity and selectivity. When the tether length was increased from 2 to 45
ethylene repeats, sensitivity decreased substantially for a neutral protein
streptavidin and slightly for a positively charged protein (avidin). In addition,
we found that two distinct avidin binding conformations were possible when using
a long tether. These conformations were sensitive to the salt concentration and
applied voltage. Finally, a longer tether resulted in reduced sensitivity due to
slower association for a monoclonal anti-biotin antibody. Our results highlight
the importance of electrostatic, electroosmotic and electrophoretic forces on
nanopore binding kinetics and sensor readout.
PMID- 27500278
TI - Predictive Modeling for Comfortable Death Outcome Using Electronic Health
Records.
AB - Electronic health record (EHR) systems are used in healthcare industry to observe
the progress of patients. With fast growth of the data, EHR data analysis has
become a big data problem. Most EHRs are sparse and multi-dimensional datasets
and mining them is a challenging task due to a number of reasons. In this paper,
we have used a nursing EHR system to build predictive models to determine what
factors impact death anxiety, a significant problem for the dying patients.
Different existing modeling techniques have been used to develop coarse-grained
as well as fine-grained models to predict patient outcomes. The coarse-grained
models help in predicting the outcome at the end of each hospitalization, whereas
fine-grained models help in predicting the outcome at the end of each shift,
therefore providing a trajectory of predicted outcomes. Based on different
modeling techniques, our results show significantly accurate predictions, due to
relatively noise-free data. These models can help in determining effective
treatments, lowering healthcare costs, and improving the quality of end-of-life
(EOL) care.
PMID- 27500279
TI - Program ACTIVE II: Design and Methods for a Multi-Center Community-Based
Depression Treatment for Rural and Urban Adults with Type 2 Diabetes.
AB - OBJECTIVE: Depression affects one in four adults with type 2 diabetes (T2DM) and
is associated with worsened diabetes complications, increased health care costs
and early mortality. Rural and low-income urban areas, including the Appalachian
region, represent an epicenter of the T2DM epidemic. Program ACTIVE II is a
comparative effectiveness treatment trial designed to test whether a combination
of cognitive behavioral therapy (CBT) and community-based exercise (EXER) will
offer greater improvements in diabetes and depression outcomes compared to
individual treatment approaches and usual care (UC). The secondary aims are to
assess changes in cardiovascular risk factors across groups and to conduct a cost
effectiveness analysis of predicted incidence of cardiovascular complications
across groups. METHODS: The study is a 2-by-2 factorial randomized controlled
trial consisting of 4 treatment groups: CBT alone, EXER alone, combination of CBT
and EXER, and UC. Adults with T2DM for > 1 year and who meet DSM-IVTR criteria
for Major Depressive Disorder (MDD) are eligible to participate at two rural
Appalachian sites (southeastern Ohio and West Virginia) and one urban site
(Indianapolis). This type II behavioral translation study uses a community
engaged research (CEnR) approach by incorporating community fitness centers and
mental health practices as interventionists. CONCLUSIONS: This is the first study
to evaluate the comparative effectiveness of combined CBT and exercise in the
treatment of depression using community-based intervention delivery. This
approach may serve as a national model for expanding depression treatment for
patients with T2DM.
PMID- 27500280
TI - Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic
dysfunction: A case report.
AB - Hypermethioninemia may be benign, present as a nonspecific sign of nongenetic
conditions such as liver failure and prematurity, or a severe, progressive inborn
error of metabolism. Genetic causes of hypermethioninemia include mitochondrial
depletion syndromes caused by mutations in the MPV17 and DGUOK genes and
deficiencies of cystathionine beta-synthase, methionine adenosyltransferase types
I and III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase, citrin,
fumarylacetoacetate hydrolase, and adenosine kinase. Here we present a 3-year old
girl with a history of poor feeding, irritability, respiratory infections,
cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia,
sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia
and mild homocystinemia. Genetic analysis of the adenosine kinase (ADK) gene
revealed a previously unreported variant (c.479-480 GA>TG) resulting in a stop
codon (p.E160X) in ADK. A methionine-restricted diet normalized the liver
function test results and improved her hypotonia.
PMID- 27500281
TI - Interferons and HIV Infection: The Good, the Bad, and the Ugly.
AB - Whether type I interferons (IFNs) hinder or facilitate HIV disease progression is
controversial. Type I IFNs induce the production of restriction factors that
protect against mucosal HIV/SIV acquisition and limit virus replication once
systemic infection is established. However, type I IFNs also increase systemic
immune activation, a predictor of poor CD4+ T-cell recovery and progression to
AIDS, and facilitate production and recruitment of target CD4+ T cells. In
addition, type I IFNs induce CD4+ T-cell apoptosis and limit antigen-specific
CD4+ and CD8+ T-cell responses. The outcomes of type I IFN signaling may depend
on the timing of IFN-stimulated gene upregulation relative to HIV exposure and
infection, local versus systemic type I IFN-stimulated gene expression, and the
subtype of type I IFN evaluated. To date, most interventional studies have
evaluated IFNalpha2 administration largely in chronic HIV infection, and few have
evaluated the effects on tissues or the HIV reservoir. Thus, whether the effect
of type I IFN signaling on HIV disease is good, bad, or so complicated as to be
ugly remains a topic of hot debate.
PMID- 27500282
TI - Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but Does
Not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV
Infected Subjects on Antiretroviral Therapy.
AB - INTRODUCTION: Altered gastrointestinal (GI) barrier integrity and subsequent
microbial translocation may contribute to immune activation in HIV infection. We
have reported that rosuvastatin improved several markers of immune activation in
HIV+ participants, but the effect of statin treatment on markers of GI barrier
dysfunction is unknown. METHODS: SATURN-HIV is a randomized, double-blind,
placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on
markers of cardiovascular disease, inflammation, and immune activation in ART
treated patients. Gut-barrier integrity was assessed by the surrogate markers
intestinal fatty acid binding protein (I-FABP), a marker of enterocyte death, and
zonulin-1, a marker of gut epithelial cell function. Levels of lipopolysaccharide
binding protein (LBP) were measured as a marker of microbial translocation.
RESULTS: Rosuvastatin significantly reduced levels of I-FABP during the treatment
period compared to the placebo. There was no effect of rosuvastatin treatment on
levels of zonulin or LBP. Baseline levels of LBP were directly related to several
markers of immune activation in samples from all participants, including soluble
CD163, IP-10, VCAM-1, TNFR-II, and the proportion of CD4+ and CD8+ T cells
expressing CD38 and HLA-DR. Many of these relationships, however, were not seen
in the statin arm alone at baseline or over time, as inflammatory markers often
decreased and LBP levels were unchanged. CONCLUSIONS: Forty-eight weeks of
rosuvastatin treatment reduced levels of I-FABP, but did not affect levels of
zonulin or LBP. The reduction in levels of inflammatory markers that we have
reported with rosuvastatin treatment is likely mediated through other mechanisms
not related to gut integrity or microbial translocation.
PMID- 27500283
TI - Medicare and Private Insurance Variations in New Medical Technology: The Case of
Drug Eluting Stents.
AB - IMPORTANCE: Little is known about the geographic and hospital variations of the
new medical technologies in Medicare. Even less is known about these variations
for the privately insured. OBJECTIVE: To examine geographic and hospital
variations in the diffusion of drug eluting stents, comparing Medicare and
privately insured populations. DESIGN: Retrospective analyses of discharges from
the State Inpatient Databases for 11 states (2004-2005) supplemented with data on
hospital characteristics from the American Hospital Association Annual Survey.
SETTING/PARTICIPANTS: Study sample included discharges with percutaneous coronary
intervention (PCI) procedures that involved a cardiac stent. EXPOSURE: Insurance
type: Medicare versus private insurance. MAIN OUTCOME: Use of a drug eluting
stent during the PCI was our outcome variable. We estimated linear probability
models at the discharge level that related our outcome variable to patient and
hospital characteristics separately for Medicare and private insurance. To
examine variations across hospital referral regions (HRRs) and across hospitals,
our models included HRR and hospital indicators respectively. RESULTS: Our
analysis included 390,649 records (237,991 Medicare, 152,658 private insurance).
We found large HRR variations in the use of drug eluting stents in 2004 for both
payer types, the year after drug eluting stents were approved (adjusted CoV: 0.35
(Medicare); 0.24 (Private Insurance)). We also found large hospital variations in
2004 (adjusted CoV: 0.32 (Medicare); 0.29 (Private Insurance)). Between 2004 and
2005, adjusted HRR and hospital variations decreased across both payer types,
suggesting that practice styles converged as the drug eluting stents diffused and
became more common. Finally, adjusted drug eluting stent rates were highly
correlated both at the HRR and hospital level across payer types. CONCLUSION: Our
findings are consistent with the hypothesis that private insurance closely
follows the lead of Medicare in terms of medical technology coverage and
reimbursement.
PMID- 27500284
TI - Gender Differences in Community-acquired Meningitis in Adults: Clinical
Presentations and Prognostic Factors.
AB - Community-acquired meningitis is a serious disease that is associated with high
morbidity and mortality. The purpose of this study was to investigate the gender
differences involved with the clinical presentations of and prognostic factors
for this disease. We conducted a retrospective study of 619 adults diagnosed with
community-acquired meningitis in Houston, Texas, who were hospitalized between
2005 and 2010. Patients were categorized as male or female. Those who were
evaluated to have a Glasgow Outcome Scale score of four or less were classified
to have an adverse clinical outcome. Males consisted of 47.2% (292/619) of the
total cohort, and more often presented with coexisting medical conditions, fever,
abnormal microbiology results, and abnormalities on head computed tomography.
Females more often presented with nuchal rigidity. On logistic regression, fever,
CSF glucose <45 mg/dL, and an abnormal neurological examination were predictors
of an adverse outcome in male patients, while age greater than 60 years and an
abnormal neurological examination were associated with a poor prognosis in female
patients. Thus, community-acquired meningitis in males differs significantly from
females in regards to comorbidities, presenting symptoms and signs, abnormal
laboratory and imaging analysis, and predictors of adverse clinical outcomes.
PMID- 27500285
TI - Closing the Gap: Supporting Patients' Transition to Self-Management after
Hospitalization.
AB - Patients going home after a hospitalization face many challenges. This transition
period exposes patients to unnecessary risks related to inadequate preparation
prior to leaving the hospital, potentially leading to errors and patient harm.
Although patients engaging in self-management have better health outcomes and
increased self-efficacy, little is known about the processes in place to support
and develop these skills for patients leaving the hospital. Through qualitative
interviews and observations of 28 patients during and after their
hospitalizations, we explore the challenges they face transitioning from hospital
care to self-management. We identify three key elements in this process:
knowledge, resources, and self-efficacy. We describe how both system and
individual factors contribute to breakdowns leading to ineffective patient
management. This work expands our understanding of the unique challenges faced by
patients during this difficult transition and uncovers important design
opportunities for supporting crucial yet unmet patient needs.
PMID- 27500287
TI - Predictive Modeling for End-of-Life Pain Outcome using Electronic Health Records.
AB - Electronic health record (EHR) systems are being widely used in the healthcare
industry nowadays, mostly for monitoring the progress of the patients. EHR data
analysis has become a big data problem as data is growing rapidly. Using a
nursing EHR system, we built predictive models for determining what factors
influence pain in end-of-life (EOL) patients. Utilizing different modeling
techniques, we developed coarse-grained and fine-grained models to predict
patient pain outcomes. The coarse-grained models help predict the outcome at the
end of each hospitalization, whereas fine-grained models help predict the outcome
at the end of each shift, thus providing a trajectory of predicted outcomes over
the entire hospitalization. These models can help in determining effective
treatments for individuals and groups of patients and support standardization of
care where appropriate. Using these models may also lower the cost and increase
the quality of end-of-life care. Results from these techniques show significantly
accurate predictions.
PMID- 27500286
TI - Preliminary Evidence for Effectiveness of Resourcefulness Training in Women
Dementia Caregivers.
AB - Nearly 10 million women in the U.S. are caregivers for an elder with dementia,
which often produces overwhelming stress and adversely affects their health.
Resourcefulness training (RT) may promote the caregiver's optimal health and
continue in their caregiving role. This pilot trial of 138 women dementia
caregivers examined the effectiveness of RT on perceived stress, depressive
cognitions, and negative emotions over time. Caregivers were first randomized to
RT or no RT and then further randomized into random versus choice conditions
followed by assignment to the journal or recorder methods, thus creating eight
groups. We examined differences on perceived stress, depressive cognitions, and
negative emotions between groups: 1) RT versus no-RT, 2) choice versus random
condition; and 3) journaling versus recording. Significant time by group
interactions were found on stress (F=4.36, p<.05), depressive cognitions
(F=10.93, p<.001), and negative emotions (F=20.48, p<.001) in the RT versus no RT
group. No differences were found between the random versus choice conditions or
the journaling versus recording methods for practicing the RT skills. The results
provide evidence for the effectiveness of RT for decreasing stress, depressive
cognitions, and negative emotions in women caregivers of elders with dementia.
The findings also suggest the need for further examination of the effects of
allowing caregivers to choose a method for practicing RT in larger samples if
caregivers of elders with dementia.
PMID- 27500288
TI - Capturing the transient species at the electrode-electrolyte interface by in situ
dynamic molecular imaging.
AB - In situ time-resolved identification of interfacial transient reaction species
were captured using imaging mass spectrometry, leading to the discovery of more
complex elementary electrode reactions and providing an unprecedented
understanding of the reaction mechanism on the electrode surface and solid
electrolyte interface using dynamic molecular imaging.
PMID- 27500289
TI - Catalytic enantio- and diastereoselective Mannich reaction of alpha-substituted
isocyanoacetates and ketimines.
AB - The highly diastereo- and enantioselective Mannich addition/cyclisation reaction
of alpha-substituted isocyanoacetate ester pronucleophiles and (hetero)aryl and
alkyl methyl ketone-derived ketimines using a silver acetate and a cinchona
derived amino phosphine binary catalyst system is reported.
PMID- 27500290
TI - Enhancing alkaline hydrogen evolution reaction activity through Ni-Mn3O4
nanocomposites.
AB - Developing efficient, stable and cost-effective electrocatalysts towards hydrogen
production in alkaline environments is vital to improve energy efficiency for
water splitting. In this work, we prepared Ni-Mn3O4 nanocomposites on Ni foam
which exhibit an excellent hydrogen evolution reaction catalytic activity with a
current density (j) of 10 mA cm(-2) at an overpotential (eta) of 91 mV and show
good stability in an alkaline medium.
PMID- 27500291
TI - Plasmonic coupling of dual gold nanoprobes for SERS imaging of sialic acids on
living cells.
AB - This work reports a benzoic group functionalized gold nanoflower as a bridge
probe for both recognition of target sialic acids and assembly of poly(N
acetylneuraminic acid) modified gold nanoparticles, which leads to plasmonic
coupling of two kinds of gold nanoprobes in a single-core-multi-satellite
nanostructure to produce a sensitive surface-enhanced Raman scattering (SERS)
signal for the imaging of sialic acids on living cells.
PMID- 27500292
TI - Pd-Catalyzed oxidative isomerization of propargylic acetates: highly efficient
access to alpha-acetoxyenones via alkenyl Csp(2)-O bond-forming reductive
elimination from Pd(IV).
AB - A Pd(ii)/(iv)-catalyzed oxidative isomerization of propargylic acetates developed
for the synthesis of polysubstituted alkenyl acetates is described. The reductive
elimination of alkenyl Csp(2)-OAc bonds from Pd(IV) intermediates is achieved.
Mechanistic studies indicate that the reaction mechanism consists of trans
acetoxypalladation of a triple bond, isomerization, oxidative addition with
PhI(OAc)2 and alkenyl C-OAc bond reductive elimination.
PMID- 27500293
TI - Advances in levodopa therapy for Parkinson disease.
PMID- 27500294
TI - [Comment on "Surgical ablation of atrial fibrillation during mitral-valve
surgery"].
PMID- 27500295
TI - [Not Available].
PMID- 27500296
TI - [Not Available].
PMID- 27500297
TI - [Not Available].
PMID- 27500298
TI - Case report of aripiprazole in the treatment of adolescent stuttering.
PMID- 27500299
TI - Author Response.
PMID- 27500300
TI - Author Response.
PMID- 27500302
TI - Never walk alone: reflecting on Hillsborough.
PMID- 27500301
TI - Women's values and preferences and health state valuations for thromboprophylaxis
during pregnancy: A cross-sectional interview.
AB - BACKGROUND: Pregnant women with prior venous thromboembolism (VTE) are at risk of
recurrence. Prophylaxis with low molecular weight heparin (LWMH) reduces that
risk but is inconvenient, costly, and may be associated with increased risks of
obstetrical bleeding. The views of pregnant women, crucial when making
prophylaxis recommendations, are currently unknown. METHODS: Cross-sectional
international multicenter study. We included women with a history of VTE who were
either pregnant or planning pregnancy. We provided information regarding risk of
VTE recurrence with and without LMWH and determined participant's willingness to
receive LMWH prophylaxis through direct choice exercises, preference-elicitation
(utilities) for health states (e.g. burden of LMWH prophylaxis), and a
probability trade-off exercise. RESULTS: Of 123 women, more women at high risk
than those at low risk of recurrence (86.4% vs. 60.0%; p = 0.003) chose to use
LMWH. The median threshold reduction in VTE at which women were willing to accept
use of LMWH, given a 16% risk of VTE without prophylaxis, was 3% (interquartile
range: 1 to 6). Participants' evaluation of the relevant health states varied
widely and was unrelated to their direct choices to use or not use LMWH.
CONCLUSIONS: Although the majority of women with a previous VTE, pregnant or
planning pregnancy choose to take LMWH during pregnancy, a minority -and in low
risk women, a large minority- do not. Our results highlight the need for
individualized shared decision-making (SDM) in the clinical encounter, and for
guideline panels to make weak recommendations in favor of LMWH that make clear
the need for SDM.
PMID- 27500304
TI - The Perioperative Highway Code. SIGNS--Safety Initiative Group for National
Sinage.
PMID- 27500303
TI - Ambassador for patient safety and the promotion, protection and support of
cardiac theatre staff.
PMID- 27500305
TI - Equality issues.
PMID- 27500306
TI - Large Scale Flow-Mediated Formation and Potential Applications of Surface
Nanodroplets.
AB - Microscopic droplets located on a solid substrate in contact with an immiscible
liquid promise a broad range of applications in miniaturized analytical
techniques, fabrication of antireflective coatings, high-resolution near-field
imaging techniques, and many others. A simple method of producing oil
nanodroplets with desirable morphology is a bottom-up approach called solvent
exchange, where nanodroplets nucleate and grow, as a good solvent of oil is
displaced by a poor solvent. In this work, we have achieved the production of
surface nanodroplets over a large surface area on planar or curved surfaces,
guided by the principles of the solvent exchange. The droplet size is uniform
over the entire surface of a planar or curved substrate and tunable. The
production rate is extremely high at 10(6) nanodroplets per second. This advance
in the nanodroplet production provides a general platform for droplet-based
applications. Here we demonstrate that the application of surface nanodroplets in
microextraction of hydrophobic solute (dye) from its highly diluted aqueous
solution and in situ detection of the dye in a simple process, and in fabrication
of highly ordered array of microlens arrays and polymer-capped microstructures by
simple processes.
PMID- 27500307
TI - Hypoxic Preconditioning Improves the Therapeutic Potential of Aging Bone Marrow
Mesenchymal Stem Cells in Streptozotocin-Induced Type-1 Diabetic Mice.
AB - Insulin replacement is the current therapeutic option for type-1 diabetes.
However, exogenous insulin cannot precisely represent the normal pattern of
insulin secretion. Another therapeutic strategy is transplantation of pancreatic
islets, but this is limited by immune rejection, intrinsic complications, and
lack of donor availability. Stem cell therapy that results in the regeneration of
insulin-producing cells represents an attractive choice. However, with advancing
age, stem cells also undergo senescence, which leads to changes in the function
of various cellular processes that result in a decrease in the regeneration
potential of these aging stem cells. In this study, the effect of young and aging
mesenchymal stem cells (MSCs) on the regeneration of pancreatic beta cells in
streptozotocin (STZ)-induced type-1 diabetic mice was observed after hypoxic
preconditioning. Hypoxia was chemically induced by 2, 4-dinitrophenol (DNP).
Plasma insulin and glucose levels were measured at various time intervals, and
pancreatic sections were analyzed histochemically. The effect of DNP was also
analyzed on apoptosis of MSCs by flow cytometry and on gene expression of certain
growth factors by quantitative real-time reverse transcription polymerase chain
reaction (qRT-PCR). We observed that hypoxic preconditioning caused changes in
the gene expression levels of growth factors in both young and aging MSCs. Young
MSCs showed significant regeneration potential compared with the aging cells in
vivo. However, hypoxic preconditioning was able to improve the regeneration
potential of aging MSCs. It is concluded from the present study that the
regeneration potential of aging MSCs into pancreatic beta-cells can be enhanced
by hypoxic preconditioning, which causes changes in the gene expression of
certain growth factors.
PMID- 27500308
TI - Photooxidation of Tryptophan and Tyrosine Residues in Human Serum Albumin
Sensitized by Pterin: A Model for Globular Protein Photodamage in Skin.
AB - Human serum albumin (HSA) is the most abundant protein in the circulatory system.
Oxidized albumin was identified in the skin of patients suffering from vitiligo,
a depigmentation disorder in which the protection against ultraviolet (UV)
radiation fails because of the lack of melanin. Oxidized pterins, efficient
photosensitizers under UV-A irradiation, accumulate in the skin affected by
vitiligo. In this work, we have investigated the ability of pterin (Ptr), the
parent compound of oxidized pterins, to induce structural and chemical changes in
HSA under UV-A irradiation. Our results showed that Ptr is able to photoinduce
oxidation of the protein in at least two amino acid residues: tryptophan (Trp)
and tyrosine (Tyr). HSA undergoes oligomerization, yielding protein structures
whose molecular weight increases with irradiation time. The protein cross
linking, due to the formation of dimers of Tyr, does not significantly affect the
secondary and tertiary structures of HSA. Trp is consumed in the photosensitized
process, and N-formylkynurenine was identified as one of its oxidation products.
The photosensitization of HSA takes place via a purely dynamic process, which
involves the triplet excited state of Ptr. The results presented in this work
suggest that protein photodamage mediated by endogenous photosensitizers can
significantly contribute to the harmful effects of UV-A radiation on the human
skin.
PMID- 27500309
TI - Chemical composition and antimicrobial activity of fatty acid methyl ester of
Quercus leucotrichophora fruits.
AB - Natural fats and dietary oils are chief source of fatty acids and are well known
to have antimicrobial activities against various microbes. The chemical
composition and antimicrobial activities of fatty acids from fruits of white Oak
(Quercus leucotrichophora) are yet unexplored and therefore the present study for
the first time determines the fatty acid composition, and the antibacterial and
antifungal activities of fatty acid methyl esters (FAME) of the white Oak plant
found along the Himalayan region of Uttarakhand, India. The GCMS analysis
revealed the presence of higher amount of saturated fatty acids than unsaturated
fatty acids. FAME extract of fruits of Q. leucotrichophora demonstrated better
antibacterial activity against Gram-positive bacteria than the Gram-negative
bacteria. The present studies clearly establish the potential of the fruits of Q.
leucotrichophora for use in soap, cosmetics and pharmaceutical industries.
PMID- 27500310
TI - Using PacBio Long-Read High-Throughput Microbial Gene Amplicon Sequencing To
Evaluate Infant Formula Safety.
AB - Infant formula (IF) requires a strict microbiological standard because of the
high vulnerability of infants to foodborne diseases. The current study used the
PacBio single-molecule real-time (SMRT) sequencing platform to generate full
length 16S rRNA-based bacterial microbiota profiles of 30 Chinese domestic and
imported IF samples. A total of 600 species were identified, dominated by
Streptococcus thermophilus, Lactococcus lactis, and Lactococcus piscium.
Distinctive bacterial profiles were observed between the two sample groups, as
confirmed with both principal coordinate analysis and multivariate analysis of
variance. Moreover, the product whey protein nitrogen index (WPNI), representing
the degree of preheating, negatively correlated with the relative abundances of
the Bacillus genus. This study has demonstrated the application of the PacBio
SMRT sequencing platform in assessing the bacterial contamination of IF products,
which is of interest to the dairy industry for effective monitoring of microbial
quality and safety during production.
PMID- 27500311
TI - A Selective Galactose-Coumarin-Derived Galectin-3 Inhibitor Demonstrates
Involvement of Galectin-3-glycan Interactions in a Pulmonary Fibrosis Model.
AB - Synthesis of doubly 3-O-coumarylmethyl-substituted thiodigalactosides from bis-3
O-propargyl-thiodigalactoside resulted in highly selective and high affinity
galectin-3 inhibitors. Mutant studies, structural analysis, and molecular
modeling revealed that the coumaryl substituents stack onto arginine side chains.
One inhibitor displayed efficacy in a murine model of bleomycin-induced lung
fibrosis similar to that of a known nonselective galectin-1/galectin-3 inhibitor,
which strongly suggests that blocking galectin-3 glycan recognition is an
important antifibrotic drug target.
PMID- 27500312
TI - Theoretical Modeling of the Chirality Discrimination of Enantiomers by
Nanotubular Cyclic Peptides using Gas-Phase Photoelectron Spectroscopy: An ONIOM
Spectroscopic Calculations.
AB - In the present work, the chirality recognition of the enantiomers of a chiral
molecule (1-phenyl-1-propanol) interacting with a nanotubular cyclic peptide (E
type cyclic decapeptide) was investigated by their ionization in the gas phase,
theoretically. The absolute energy difference between the interaction of the S-
and R-enantiomer with the cyclic peptide, calculated at the M06-2X/6-311++G(d, p)
level of theory, was 4.70 kcal.mol(-1). Two different schemes of "Our own N
layered Integrated molecular Orbital and molecular Mechanics (ONIOM)" method such
as (quantum mechanics (QM):molecular mechanics (MM)) and (QM:QM) were employed to
study the effect of the interaction on the gas-phase ionization energies of the
enantiomers and cyclic peptide, separately. The symmetry-adapted
cluster/configuration interaction (SAC-CI) methodology was used for the
calculation of the ionization energies. It was found that the difference between
the interactions of R- and S-enantiomer with the cyclic peptide caused different
changes in the photoelectron spectrum of each enantiomer so that these changes
could be used for the chirality discrimination of the enantiomers in the gas
phase. Similarly, the photoelectron spectrum of the cyclic peptide interacting
with the R and S-enantiomer were calculated, separately, and it was observed that
the difference in the interaction with the R- and S-enantiomer created different
changes in the spectrum of cyclic peptide. Finally, it was shown that the
difference in the interaction of cyclic peptide with the enantiomers of a chiral
molecule in the gas phase can be used for the identification of enantiomers in
the gas phase by the direct ionization.
PMID- 27500314
TI - Octanuclear Heterobimetallic {Ni4Ln4} Assemblies Possessing Ln4 Square Grid [2 *
2] Motifs: Synthesis, Structure, and Magnetism.
AB - Octanuclear heterobimetallic complexes, [Ln4Ni4(H3L)4(MU3-OH)4(MU2
OH)4]4Cl.xH2O.yCHCl3 (Dy(3+), x = 30.6, y = 2 (1); Tb(3+), x = 28, y = 0 (2) ;
Gd(3+), x = 25.3, y = 0 (3); Ho(3+), x = 30.6, y = 3 (4)) (H5L = N1,N3-bis(6
formyl-2-(hydroxymethyl)-4-methylphenol)diethylenetriamine) are reported. These
are assembled by the cumulative coordination action of four doubly deprotonated
compartmental ligands, [H3L](2-), along with eight exogenous -OH ligands. Within
the core of these complexes, four Ln(3+)'s are distributed to the four corners of
a perfect square grid while four Ni(2+)'s are projected away from the plane of
the Ln4 unit. Each of the four Ni(2+)'s possesses distorted octahedral geometry
while all of the Ln(3+)'s are crystallographically equivalent and are present in
an elongated square antiprism geometry. The magnetic properties of compound 3 are
dominated by an easy-plane single-ion anisotropy of the Ni(2+) ions [DNi = 6.7(7)
K] and dipolar interactions between Gd(3+) centers. Detailed ac magnetometry
reveals the presence of distinct temperature-dependent out-of-phase signals for
compounds 1 and 2, indicative of slow magnetic relaxation. Magnetochemical
analysis of complex 1 implies the 3d and the 4f metal ions are engaged in
ferromagnetic interactions with SMM behavior, while dc magnetometry of compound 2
is suggestive of an antiferromagnetic Ni-Tb spin-exchange with slow magnetic
relaxation due to a field-induced level crossing. Compound 4 exhibits an easy
plane single-ion anisotropy for the Ho(3+) ions and weak interactions between
spin centers.
PMID- 27500313
TI - Nucleophilic (Radio)Fluorination of alpha-Diazocarbonyl Compounds Enabled by
Copper-Catalyzed H-F Insertion.
AB - The copper-catalyzed H-F insertion into alpha-diazocarbonyl compounds is
described using potassium fluoride (KF) and hexafluoroisopropanol. Access to
complex alpha-fluorocarbonyl derivatives is achieved under mild conditions, and
the method is readily adapted to radiofluorination with [(18)F]KF. This late
stage strategy provides an attractive route to (18)F-labeled biomolecules.
PMID- 27500315
TI - Current Resources for Evidence-Based Practice, September/October 2016.
PMID- 27500316
TI - Thoracic dimples and dysmorphic features associated with a partial duplication
and triplication of chromosome 12q24.
PMID- 27500317
TI - Aminolevulinic Acid-Mediated Photodynamic Therapy Causes Cell Death in MG-63
Human Osteosarcoma Cells.
AB - OBJECTIVE: The aim of this study was to test the efficacy of aminolevulinic acid
mediated photodynamic therapy (PDT) against the human osteosarcoma cell line MG
63. BACKGROUND DATA: Osteosarcoma is the most common type of primary malignant
bone tumor diagnosed in the United States among adolescents and children.
Treatments for osteosarcoma often result in diminished limb use or amputation.
Because ALA-mediated PDT exhibits dual specificity in the context of tumor
killing, this therapy could represent a less invasive, but effective, treatment
for this disease. MATERIALS AND METHODS: To assess ALA dark toxicity in MG-63
cells, cells were incubated with varying concentrations of ALA, and cell
viability was determined by crystal violet assay. Protoporphyrin IX (PpIX)
accumulation was assessed subsequent to ALA incubation at various concentrations
using spectrofluorometry. Cell death subsequent to ALA-PDT was determined by
illuminating cells at a wavelength of 635 nm at various light intensities
subsequent to ALA incubation. Cell viability was assessed using the MTT assay.
RESULTS: ALA dark toxicity was observed only at the highest concentrations of 2,
5, and 10 mM. Maximal PpIX concentration was observed at 0.5 and 1 mM ALA,
subsequent to a 24-h incubation. Maximal cell death with minimal light toxicity
was observed at 0.5 and 1 mM ALA after illumination with 0.6 and 3 J/cm(2) light.
CONCLUSIONS: Collectively, our data indicate that ALA-PDT can result in the death
of MG-64 human osteosarcoma cells in vitro.
PMID- 27500318
TI - Angiogenic imbalance as a contributor to the pathophysiology of preeclampsia
among black African women.
AB - OBJECTIVE: The pathogenesis of preeclampsia remains unclear despite extensive
research. Altered angiogenic balance has been hypothesized to play a significant
role in the clinical manifestations of this syndrome. However this imbalance has
not been investigated extensively among black African women. The aim of this
study was to investigate the maternal levels of the angiogenic factors soluble
vascular endothelial growth factor receptor 1 (sFLT1) and placental growth factor
(PlGF) among black African women with preeclampsia. METHODS: A case control study
was conducted in the Mthatha hospital complex in South Africa including 51 women
with preeclampsia and 82 women with uncomplicated pregnancies. Blood samples were
drawn from participants and serum was used to assess sFLT1, and PlGF levels
quantified using specific enzyme linked immunosorbent assays. Non- parametric
statistics were used for analysis. RESULTS: Black African women with preeclampsia
were found to have significantly lower levels of PlGF (90.3 +/- 8.9 pg/ml versus
172.8 +/- 20.2 pg/ml; p < 0.01), higher sFLT1 (2087.3 +/- 200.1 pg/ml versus
1546.5 +/- 91.9 pg/ml; p < 0.01) and a higher sFLT1/PIGF ratio (66.8 +/- 18.7
versus 22.3 +/- 2.9; p < 0.01) compared to black African normotensive controls.
CONCLUSION: The results support an altered angiogenic balance may contribute to
the pathogenesis/pathophysiology of preeclampsia among black African women as
reported in other populations.
PMID- 27500319
TI - Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery
Model in the Swine.
AB - To date, many pharmacological agents used to treat or prevent arrhythmias in open
heart cases create undesired systemic side effects. For example, antiarrhythmic
drugs administered intravenously can produce drops in systemic pressure in the
already compromised cardiac patient. While performing open-heart procedures,
surgeons will often either create a small port or form a pericardial cradle to
create suitable fields for operation. This access yields opportunities for target
pharmacological delivery (antiarrhythmic or ischemic preconditioning agents)
directly to the myocardial tissue without undesired side effects. We have
developed a swine model for testing pharmacological agents for target delivery
within the pericardial fluid. While fully anesthetized, each animal was
instrumented with a Swan-Ganz catheter as well as left and right ventricle
pressure catheters, and pacing leads were placed in the right atrial appendage
and the right ventricle. A medial sternotomy was then performed and a pericardial
access cradle was created; a plunge pacing lead was placed in the left atrial
appendage and a bipolar pacing lead was placed in the left ventricle. Utilizing a
programmer and a cardiac mapping system, the refractory period of the
atrioventricular node (AVN), atria and ventricles was determined. In addition,
atrial fibrillation (AF) induction was produced utilizing a Grass stimulator and
time in AF was observed. These measurements were performed prior to treatment, as
well as 30 min and 60 min after pericardial treatment. Additional time points
were added for selected studies. The heart was then cardiopleged and reanimated
in a four chamber working mode. Pressure measurements and function were recorded
for 1 hr after reanimation. This treatment strategy model allowed us to observe
the effects of pharmacological agents that may decrease the incidence of cardiac
arrhythmias and/or ischemic damage, during and after open-heart surgery.
PMID- 27500320
TI - Genetic and Biochemical Approaches for In Vivo and In Vitro Assessment of Protein
Oligomerization: The Ryanodine Receptor Case Study.
AB - Oligomerization is often a structural requirement for proteins to accomplish
their specific cellular function. For instance, tetramerization of the ryanodine
receptor (RyR) is necessary for the formation of a functional Ca(2+) release
channel pore. Here, we describe detailed protocols for the assessment of protein
self-association, including yeast two-hybrid (Y2H), co-immunoprecipitation (co
IP) and chemical cross-linking assays. In the Y2H system, protein self
interaction is detected by beta-galactosidase assay in yeast co-expressing GAL4
bait and target fusions of the test protein. Protein self-interaction is further
assessed by co-IP using HA- and cMyc-tagged fusions of the test protein co
expressed in mammalian HEK293 cells. The precise stoichiometry of the protein
homo-oligomer is examined by cross-linking and SDS-PAGE analysis following
expression in HEK293 cells. Using these different but complementary techniques,
we have consistently observed the self-association of the RyR N-terminal domain
and demonstrated its intrinsic ability to form tetramers. These methods can be
applied to protein-protein interaction and homo-oligomerization studies of other
mammalian integral membrane proteins.
PMID- 27500321
TI - Current Diagnosis and Management of Pelvic Fistulae in Women.
AB - Pelvic fistulae are an abnormal communication among the genitourinary tract, the
gastrointestinal tract, and the vagina or perineum. Genital tract fistulae have
been described in the medical literature for the past several thousand years.
Advancements in both the diagnosis and treatment of vaginal fistulae have been
obtained over the past century as surgical interventions have become safer and
surgical techniques have improved. The most common cause of fistulae worldwide is
obstructed labor. In developed countries, fistulae most commonly occur after
benign gynecologic surgery, but obstructed labor, malignancy, radiation exposure,
and inflammatory bowel disease can also cause fistulae. Fistulae significantly
affect quality of life. Diagnostic studies and radiologic imaging can help aid
the diagnosis, but a thorough physical examination is the most important
component in the evaluation and diagnosis of a fistula. Temporizing treatments
are available to help ease patient suffering until surgical management can be
performed. Surgical repairs can be performed using an abdominal, vaginal, or
transanal approach. Although technically challenging, surgical repair is usually
successful, but closure of the fistula tract does not guarantee continence of
urine or feces, because there is often underlying damage to the bowel and
bladder.
PMID- 27500322
TI - Forceps, Simulation, and Social Media.
PMID- 27500323
TI - Drilling Down on Maternal Mortality.
PMID- 27500324
TI - What Is New in the Prevention of Preeclampsia?: Best Articles From the Past Year.
AB - This month we focus on current research in prevention of preeclampsia. Dr. Norton
discusses five recent publications, which are concluded with a "bottom line" that
is the take-home message. The complete reference for each can be found in on this
page, along with direct links to the abstracts.
PMID- 27500325
TI - Connect the Dots-September 2016.
PMID- 27500326
TI - Differences in Serum Human Chorionic Gonadotropin Rise in Early Pregnancy by Race
and Value at Presentation.
AB - OBJECTIVE: To assess whether variation in serum human chorionic gonadotropin
(hCG) measures, used to assess early gestation viability, are associated with
differences in clinical presentation and patient factors. METHOD: This
retrospective cohort study included 285 women with first-trimester pain and
bleeding and a pregnancy of unknown location for whom a normal intrauterine
pregnancy was ultimately confirmed. Serial samples were collected at three U.S.
sites and hCG changes were analyzed for differences by race, ethnicity, and
clinical factors. A nonlinear, mixed-effects regression model was used assuming a
random subject shift in the time axis. RESULTS: The hCG rise in symptomatic women
with ongoing intrauterine pregnancy differs by patient factors and level at
presentation. The 2-day minimum (first percentile) rise in hCG was faster when
presenting hCG values were low and slower when presenting hCG value was high.
African American women had a faster hCG rise (P<.001) compared with non-African
American women. Variation in hCG curves was associated with prior miscarriage
(P=.014), presentation of bleeding (P<.001), and pain (P=.002). For initial hCG
values of less than 1,500, 1,500-3,000 and greater than 3,000 milli-international
units/mL, the predicted 2-day minimal (first percentile) rise was 49%, 40%, and
33%, respectively. CONCLUSION: The rise of hCG levels in women with viable
intrauterine pregnancies and symptoms of potential pregnancy failure varies
significantly by initial value. Changes in hCG rise related to race should not
affect clinical care. To limit interruption of a potential desired intrauterine
pregnancy, a more conservative "cutoff" (slower rise) is needed when hCG values
are high. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
https://clinicaltrials.gov, NCT00194168.
PMID- 27500327
TI - Unilateral Human Papillomavirus Infection and Cervical Dysplasia in a Patient
With Two Cervices.
AB - BACKGROUND: In a uterine didelphys with two cervices, cervical screening may not
reveal the same abnormalities. CASE: We present a patient with a uterine
didelphys with two cervices in a single vagina after resection of a longitudinal
vaginal septum at age 12. She presented with abnormal Pap test results with the
right and left cervices discordant from each other. Despite both cervices sharing
stroma in the midline, her right cervix was negative for human papillomavirus
(HPV) and dysplasia, while her left cervix was HPV positive with high-grade
cervical dysplasia on an excisional specimen. CONCLUSION: Uterine didelphys with
shared bilateral cervices will not necessarily share the same HPV status or have
concordant dysplasia.
PMID- 27500328
TI - Reverse Vesicouterine Fold Dissection for Laparoscopic Hysterectomy After Prior
Cesarean Deliveries.
AB - BACKGROUND: Cesarean delivery adhesions, during laparoscopic hysterectomy, can
present surgical challenges, including distortion of anatomy, prolonged operating
time, and inadvertent injury to nearby structures. TECHNIQUE: At the time of
laparoscopic hysterectomy, in patients with significant adhesions from prior
cesarean deliveries, we use a reverse inferior to superior vesicouterine fold
dissection to mobilize the scarred bladder. We use this as an alternative to the
commonly practiced technique of mobilizing the bladder in a superior to inferior
fashion at the time of laparoscopic hysterectomy. EXPERIENCE: Fifty-two patients
with a median age of 42.5 years are presented. Forty-eight patients were
discharged within 3-6 hours postoperatively. Sixteen patients were discharged
with Foley catheters, because they were unable to void within the protocol for a
fast-track discharge. The catheters were removed between postoperative days 1 and
5. There were no gastrointestinal or genitourinary complications. One patient
experienced a delayed vaginal cuff abscess and bleeding, which were managed
conservatively. CONCLUSION: Reverse vesicouterine fold dissection is a useful
alternative technique for laparoscopic hysterectomy in women with a history of
prior cesarean deliveries.
PMID- 27500330
TI - Disparities in Surgical Care Among Women With Endometrial Cancer.
AB - OBJECTIVE: To analyze contemporary U.S. use of minimally invasive surgery for the
treatment of endometrial cancer and associated inpatient complications and costs.
METHODS: In this retrospective cohort study, the National Inpatient Sample
database was analyzed in patients with nonmetastatic endometrial cancer who
underwent hysterectomy during 2012-2013. Hierarchical multiple logistic
regression and propensity score matching were used to compare complications among
patients treated with open compared with minimally invasive hysterectomy surgery.
Cost of care was also compared using generalized linear modeling. RESULTS: We
identified 9,799 patients; 52.4% underwent open and 47.6% minimally invasive
hysterectomy. Many patients (43.4%) were treated at low-volume hospitals (less
than 10 endometrial cancer cases annually). Patients were less likely to undergo
open surgery in high-volume compared with low-volume hospitals (51.8% compared
with 58.1%, respectively; adjusted odds ratio [OR] 0.35, 95% confidence interval
[CI] 0.13-0.94) and more likely to undergo open surgery in rural compared with
urban teaching hospitals (75.6% compared with 51.1%, respectively; adjusted OR
14.34, 95% CI 9.66-21.27), government compared with nonprofit hospitals (61.3%
compared with 51.1%, respectively; adjusted OR 1.66, 95% CI 1.15-2.39), and in
patients of black (67.9%; OR 1.46, 95% CI 1.30-1.65) and "other" race (60.5%;
adjusted OR 2.39, 95% CI 1.99-2.87) compared with white race (49.2%, referent).
Open surgery was associated with increased perioperative complications (adjusted
OR 2.80, 95% CI 2.48-3.17) and a $1,243 increase in cost per case compared with
minimally invasive approaches (P<.001). Using minimally invasive surgery for 80%
of study patients may have averted 2,733 complications and saved approximately
$19 million. CONCLUSION: Most U.S. women with endometrial cancer continue to be
treated with open hysterectomy surgery despite increased complication rates and
financial costs associated with this approach. A disparity in endometrial cancer
surgical care exists that is affected by patient race and hospital geography and
cancer volumes.
PMID- 27500329
TI - Second Curettage for Low-Risk Nonmetastatic Gestational Trophoblastic Neoplasia.
AB - OBJECTIVE: To evaluate the efficacy and safety of second uterine curettage in
lieu of chemotherapy for patients with low-risk, nonmetastatic gestational
trophoblastic neoplasia (GTN) and to evaluate whether response to second
curettage is independent of patient age, World Health Organization (WHO) risk
score, registration human chorionic gonadotropin (hCG) level, lesion size, and
depth of myometrial invasion measured on ultrasound examination. METHODS: This
was a cooperative group multicenter prospective phase II study. Prestudy testing
included quantitative hCG level, pelvic ultrasonography, and chest radiography.
Patients were categorized according to WHO risk scoring criteria (low risk with a
score of 0-6). RESULTS: Sixty-four women with newly diagnosed low-risk,
nonmetastatic GTN were enrolled. Four patients were excluded. Twenty-four
patients (40%) (lower 95% confidence limit 27.6%) were cured after second
curettage. An additional two patients (3%) achieved a complete response but did
not complete follow-up. Overall, 26 of 60 patients were able to avoid
chemotherapy. Surgical failure was observed in 34 women (59%) and was more common
in women 19 years old or younger or 40 years old or older. One case of grade 1
uterine perforation was successfully managed by observation. Four grade 1 and one
grade 3 uterine hemorrhages were reported. New metastatic disease (lung) was
identified in one of these women after second curettage. In three patients
(surgical failures), the second curettage pathology was placental site
trophoblastic tumor, and it was placental nodule in one additional patient.
CONCLUSION: Second uterine curettage as initial treatment for low-risk,
nonmetastatic GTN cures 40% of patients without significant morbidity. CLINICAL
TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT00521118.
PMID- 27500331
TI - Surgical Management of a Heterotopic Cesarean Scar Pregnancy With Preservation of
an Intrauterine Pregnancy.
AB - BACKGROUND: Spontaneously conceived heterotopic pregnancies are rare. A
heterotopic cesarean scar pregnancy involves an intrauterine pregnancy and a
second pregnancy in the cesarean scar. Treatment approaches include both medical
and surgical management. We present a surgical approach to the treatment of a
heterotopic cesarean scar pregnancy with preservation of an intrauterine
gestation. CASE: A 29-year-old woman, gravida 4 para 1021, presented at 5 weeks
of gestation with spotting. Ultrasonography revealed a heterotopic cesarean scar
pregnancy. The patient underwent resection of the ectopic pregnancy through
minilaparotomy in an attempt to conserve the intrauterine pregnancy. She
subsequently delivered an early-term neonate. CONCLUSION: Laparotomy with
resection of the ectopic pregnancy is an option for treatment of an early
heterotopic cesarean scar pregnancy when the patient desires conservation of the
intrauterine pregnancy. Excision was not associated with pregnancy complications.
PMID- 27500332
TI - Atypical Endometrial Polyps and Concurrent Endometrial Cancer: A Systematic
Review.
AB - OBJECTIVE: To estimate the risk of concurrent endometrial cancer in nonpolypoid
endometrium when atypia was diagnosed within an endometrial polyp. DATA SOURCES:
MEDLINE, EMBASE, Web of Science, and ClinicalTrials.gov were searched for studies
published between 1990 and January 2015 in which 1) women with atypical
hyperplastic endometrial polyps underwent a consecutive hysterectomy; or 2) the
natural behavior of endometrium with concurrent atypical endometrial polyps was
evaluated. METHODS OF STUDY SELECTION: Studies were selected when at least one
patient within each study was initially diagnosed with an atypical endometrial
polyp for which follow-up pathology was available. RESULTS: Broad searches
yielded 2,922 authentic citations, 307 met criteria for full-text evaluation, and
10 met inclusion criteria. Two authors independently reviewed articles and
consensus was reached. The final selection included eight retrospective studies
reporting on concurrent endometrial cancer in case of atypical endometrial polyps
and two follow-up studies on patients conserving their uterus after hysteroscopic
resection of atypical endometrial polyps. In total, 127 patients were included
with an initial diagnosis of atypical endometrial hyperplasia within polyps. Meta
analysis showed a pooled risk estimate of 5.6% (95% confidence interval [CI] 0.2
17.6%) on concurrent endometrial cancer after resection of an atypical
endometrial polyp. CONCLUSION: The pooled risk estimate of 5.6% (95% CI 0.2
17.6%) on endometrial cancer when atypia is found within an endometrial polyp
differs from the well-established risk of nonpolypoid atypical endometrial
hyperplasia on endometrial cancer of up to 42%. This risk of endometrial cancer
is important in the process of shared decision-making regarding follow-up and
further treatment.
PMID- 27500334
TI - Simulation Training for Forceps-Assisted Vaginal Delivery and Rates of Maternal
Perineal Trauma.
AB - OBJECTIVE: To evaluate the association of a forceps simulation training
curriculum for obstetrics residents on rates of severe perineal lacerations after
forceps deliveries. METHODS: This was a retrospective cohort study. We created a
novel simulation curriculum for forceps-assisted vaginal delivery based on the
best practices of local experts, and trained all residents beginning in 2013. We
then retrospectively reviewed all forceps deliveries performed in the 2.5 years
after initiation of the training and the 7.5 years before the training program.
We identified patients who experienced a severe perineal laceration (third- or
fourth-degree) and examined the relationship of resident training status and
perineal laceration. Known risk factors for lacerations were identified and a
multilevel multivariable model was created including these factors as well as
resident training. RESULTS: During the study period, we identified 6,058 forceps
assisted vaginal deliveries. We examined temporal trends in rates of forceps of
severe perineal laceration. We identified a decrease in severe lacerations
between 2005 and 2008, ending 5 years before the initiation of the training
curriculum. These years were censored from the data, yielding a baseline
observational period of 4,279 deliveries with no significant trend in laceration
rate. Univariate analysis reveals a 22% reduction in severe perineal laceration
(odds ratio [OR] 0.78; P=.005) among women delivered by residents who had
completed forceps simulation training compared with women delivered by residents
who had not. After adjusting for known maternal and delivery risk factors for
perineal laceration, the magnitude of the reduction increased to 26% in the full
data set model (OR 0.74; P=.002). CONCLUSION: A forceps simulation curriculum for
obstetrics residents was associated with a significant reduction in severe
perineal lacerations.
PMID- 27500333
TI - Recent Increases in the U.S. Maternal Mortality Rate: Disentangling Trends From
Measurement Issues.
AB - OBJECTIVE: To develop methods for trend analysis of vital statistics maternal
mortality data, taking into account changes in pregnancy question formats over
time and between states, and to provide an overview of U.S. maternal mortality
trends from 2000 to 2014. METHODS: This observational study analyzed vital
statistics maternal mortality data from all U.S. states in relation to the format
and year of adoption of the pregnancy question. Correction factors were developed
to adjust data from before the standard pregnancy question was adopted to promote
accurate trend analysis. Joinpoint regression was used to analyze trends for
groups of states with similar pregnancy questions. RESULTS: The estimated
maternal mortality rate (per 100,000 live births) for 48 states and Washington,
DC (excluding California and Texas, analyzed separately) increased by 26.6%, from
18.8 in 2000 to 23.8 in 2014. California showed a declining trend, whereas Texas
had a sudden increase in 2011-2012. Analysis of the measurement change suggests
that U.S. rates in the early 2000s were higher than previously reported.
CONCLUSION: Despite the United Nations Millennium Development Goal for a 75%
reduction in maternal mortality by 2015, the estimated maternal mortality rate
for 48 states and Washington, DC, increased from 2000 to 2014; the international
trend was in the opposite direction. There is a need to redouble efforts to
prevent maternal deaths and improve maternity care for the 4 million U.S. women
giving birth each year.
PMID- 27500335
TI - Association Between Western and Mediterranean Dietary Patterns and Mammographic
Density.
AB - OBJECTIVE: To examine the association between two dietary patterns (Western and
Mediterranean), previously linked to breast cancer risk, and mammographic
density. METHODS: This cross-sectional study included 3,584 women attending
population-based breast cancer screening programs and recruited between October
7, 2007, and July 14, 2008 (participation rate 74.5%). Collected data included
anthropometric measurements; demographic, obstetric, and gynecologic
characteristics; family and personal health history; and diet in the preceding
year. Mammographic density was blindly assessed by a single radiologist and
classified into four categories: less than 10%, 10-25%, 25-50%, and greater than
50%. The association between adherence to either a Western or a Mediterranean
dietary pattern and mammographic density was explored using multivariable ordinal
logistic regression models with random center-specific intercepts. Models were
adjusted for age, body mass index, parity, menopause, smoking, family history,
hormonal treatment, and calorie and alcohol intake. Differences according to
women's characteristics were tested including interaction terms. RESULTS: Women
with a higher adherence to the Western dietary pattern were more likely to have
high mammographic density (n=242 [27%]) than women with low adherence (n=169
[19%]) with a fully adjusted odds ratio (ORQ4vsQ1) of 1.25 (95% confidence
interval [CI] 1.03-1.52). This association was confined to overweight-obese women
(adjusted ORQ4vsQ1 [95% CI] 1.41 [1.13-1.76]). No association between
Mediterranean dietary pattern and mammographic density was observed. CONCLUSION:
The Western dietary pattern was associated with increased mammographic density
among overweight-obese women. Our results might inform specific dietary
recommendations for women with high mammographic density.
PMID- 27500336
TI - Antenatal Corticosteroids for the Prevention of Respiratory Distress Syndrome in
Premature Twins.
AB - OBJECTIVE: To estimate whether antenatal corticosteroids before 34 weeks of
gestation are associated with reduced incidence of respiratory distress syndrome
(RDS) and composite neonatal morbidity in preterm twins. METHODS: This was a
secondary analysis of a multicenter randomized trial for the prevention of
preterm birth in multiple gestations. All liveborn, nonanomalous twins delivered
between 24 0/7 and 36 6/7 weeks of gestation were included. Neonatal outcomes
were compared between women who received antenatal corticosteroids and those who
did not. The primary outcome was the incidence of RDS. The secondary outcome was
the incidence of serious composite neonatal morbidity. Multivariable log Poisson
regression with correlation adjustment between twins born to the same mother was
performed for confounder control. Adjusted relative risks (RRs) are reported for
study outcomes. Based on a post hoc power analysis, this study was powered to
detect an RR less than 0.63 for RDS and greater than 1.43 for composite neonatal
morbidity outcomes. RESULTS: A total of 432 women (850 neonates) were included.
Only 300 (35%) neonates were born to women receiving antenatal corticosteroids.
After multivariable regression, antenatal corticosteroids were not associated
with a reduced incidence of RDS (81 [27%] compared with 92 [17%] neonates,
adjusted RR 1.28, 95% confidence interval [CI] 0.97-1.71) or composite neonatal
morbidity (87 [29%] compared with 108 [20%] neonates, adjusted RR 1.21, 95% CI
0.93-1.56). However, antenatal corticosteroids were associated with increased
rates of neonatal intensive care unit admissions (235 [78%] compared with 322
[59%] neonates, adjusted RR 1.22, 95% CI 1.09-1.36) and mechanical ventilation
(70 [23%] compared with 66 [12%] neonates, adjusted RR 1.52, 95% CI 1.12-2.09).
Focusing analysis to newborns delivered before 34 weeks of gestation (n=311), 161
(52%) received antenatal corticosteroids. Similarly, no differences in the rate
of RDS (66 [41%] compared with 68 [45%] neonates, adjusted RR 1.01, 95% CI 0.76
1.34) or composite neonatal morbidity (72 [45%] compared with 81 [54%] neonates,
adjusted RR 0.95, 95% CI 0.74-1.22) were noted. CONCLUSION: In this cohort of
preterm twins, antenatal corticosteroid administration was not associated with a
reduced incidence of RDS and composite neonatal morbidity.
PMID- 27500337
TI - Enhanced Recovery Implementation in Major Gynecologic Surgeries: Effect of Care
Standardization.
AB - OBJECTIVE: To examine implementing an enhanced recovery after surgery (ERAS)
protocol for women undergoing major gynecologic surgery at an academic
institution and compare surgical outcomes before and after implementation.
METHODS: Two ERAS protocols were developed: a full pathway using regional
anesthesia for open procedures and a light pathway without regional anesthesia
for vaginal and minimally invasive procedures. Enhanced recovery after surgery
pathways included extensive preoperative counseling, carbohydrate loading and
oral fluids before surgery, multimodal analgesia with avoidance of intravenous
opioids, intraoperative goal-directed fluid resuscitation, and immediate
postoperative feeding and ambulation. A before-and-after study design was used to
compare clinical outcomes, costs, and patient satisfaction. Complications and
risk-adjusted length of stay were drawn from the American College of Surgeons'
National Surgical Quality Improvement Program database. RESULTS: On the ERAS full
protocol, 136 patients were compared with 211 historical controls and the median
length of stay was reduced (2.0 compared with 3.0 days; P=.007) despite an
increase in National Surgical Quality Improvement Program-predicted length of
stay (2.5 compared with 2.0 days; P=.009). Reductions were seen in median
intraoperative morphine equivalents (0.3 compared with 12.7 mg; P<.001),
intraoperative (285 compared with 1,250 mL; P<.001) and total intravenous fluids
(-917.5 compared with 1,410 mL; P<.001), immediate postoperative pain scores (3.7
compared with 5.0; P<.001), and total complications (21.3% compared with 40.2%;
P=.004). On the ERAS light protocol, 249 patients were compared with 324
historical controls and demonstrated decreased intraoperative and postoperative
morphine equivalents (0.0 compared with 13.0 mg; P<.001 and 15.0 compared with
23.6 mg; P<.001) and decreased intraoperative and overall net intravenous fluids
(P<.001). Patient satisfaction scores showed a marked and significant improvement
on focus questions regarding pain control, nurses keeping patients informed, and
staff teamwork; 30-day total hospital costs were significantly decreased in both
ERAS groups. CONCLUSION: Implementation of ERAS protocols in gynecologic surgery
was associated with a substantial decrease in intravenous fluids and morphine
administration coupled with reduction in length of stay for open procedures
combined with improved patient satisfaction and decreased hospital costs.
PMID- 27500338
TI - Polyethylene Glycol 3350 and Docusate Sodium Compared With Docusate Sodium Alone
After Urogynecologic Surgery: A Randomized Controlled Trial.
AB - OBJECTIVE: To compare time to first bowel movement and additional
gastrointestinal outcomes between women receiving polyethylene glycol 3350
(PEG3350) and docusate sodium and docusate sodium alone after urogynecologic
surgery. METHODS: Participants received twice-daily 100 mg docusate sodium and
were randomized to daily 1) PEG3350 or 2) inert placebo for 5 days after
urogynecologic surgery. They completed bowel diaries, Bristol stool scale,
validated Patient Assessment of Constipation Symptom Questionnaire, and Patient
Assessment of Constipation Quality-of-Life Questionnaire preoperatively and 1
week after surgery. Our primary outcome was time to first bowel movement after
surgery. To detect a 1-day difference in time to first bowel movement (4 compared
with 3 days), 63 participants were needed in each group. RESULTS: From September
2012 through March 2015, 145 women were randomized and 131 (90%) analyzed: 66
received PEG3350, and 65 received placebo. Polyethylene glycol 3350 did not
significantly reduce time to first bowel movement after surgery compared with
placebo (2.77 days [interquartile range 1.86-3.40] compared with 2.92 days
[interquartile range 1.85-4.02] P=.25). Women in the PEG3350 group were less
likely to take additional laxatives postoperatively, and the PEG3350 group was
more adherent to the study drug regimen. Questionnaire scores, fecal
incontinence, and urgency were similar between groups. CONCLUSION: In women
taking routine docusate sodium after urogynecologic surgery, adding PEG3350
postoperatively did not reduce time to first bowel movement. CLINICAL TRIAL
REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01691742.
PMID- 27500339
TI - Outcomes and Postoperative Complications After Hysterectomies Performed for
Benign Compared With Malignant Indications.
AB - OBJECTIVE: To compare complications and outcomes after hysterectomy for benign
compared with malignant indications in the United States. METHODS: Women who
underwent hysterectomy in the United States for either benign or malignant
indications from January 2008 to December 2012 were retrospectively identified
using the National Surgical Quality Improvement Program database. Patients were
excluded if the procedure was not performed for primary gynecologic indications.
Appropriate procedures were identified using Current Procedural Terminology and
International Classification of Diseases, 9th Revision codes. Univariate and
multivariable models for complication risk were estimated using logistic
regression. RESULTS: We identified 59,525 eligible patients, with 49,331 (82.9%)
hysterectomies performed for benign and 10,194 (17.1%) for malignant indications.
All complications, including wound complications (2.5% benign compared with 5.5%
malignant, P<.001), venous thromboembolism (0.33% compared with 1.7%, P<.001),
urinary tract infection (2.7% compared with 3.2%, P=.009), sepsis (0.53% compared
with 1.9%, P<.001), blood transfusion (2.6% compared with 11.5%, P<.001), death
(0.02% compared with 0.10%, P<.001), unplanned readmission (1.8% compared with
4.5%, P<.001), and returns to the operating room (0.91% compared with 1.4%,
P<.001), were significantly more common for malignant hysterectomies. The overall
rate of complications for benign cases was 7.9% compared with a rate of 19.4% for
malignant hysterectomy. The median operating time for laparoscopy in benign cases
was significantly longer than for open or vaginal hysterectomy procedures (127
minutes compared with 105 or 94 minutes, respectively; P<.001). The median
operating time in malignant cases was significantly longer than for benign cases
(P<.001). CONCLUSION: Hysterectomies performed for gynecologic malignancies are
associated with a more than twofold higher complication rate compared with those
performed for benign conditions. Minimally invasive surgery is associated with a
decreased complication rate compared with open surgery. These data can be used
for patient counseling and surgical planning, determining physician and hospital
costs of care, and considered when assigning value-based reimbursement.
PMID- 27500340
TI - Higher Risk of Homicide Among Pregnant and Postpartum Females Aged 10-29 Years in
Illinois, 2002-2011.
AB - OBJECTIVE: To examine whether being pregnant or postpartum was associated with
excess risk for homicide among females in Illinois and to describe the
association between pregnancy status and homicide by race, ethnicity, and age
group. METHODS: This is a retrospective, multicohort, ecologic study of females
of reproductive age in Illinois between 2002 and 2011 using Illinois Department
of Public Health maternal mortality data and vital records data. We compared
pregnancy-associated homicides with live births using chi tests. Among maternal
deaths in the state, we calculated mortality rates per 100,000 live births for
homicide and other violent causes and the leading direct obstetric causes. We
calculated aggregate, pregnancy-associated, and nonpregnancy associated homicide
rates stratified by race or ethnicity and age group. RESULTS: There were 636
pregnancy-associated deaths in Illinois from 2002 to 2011. Of these, 82 (13%)
were the result of homicide (5.0 [95% confidence interval (CI) 4.0-6.2]/100,000
live births). There were 931 homicides among females of reproductive age not
associated with pregnancy (2.88 [95% CI 2.70-3.07]/100,000 population). More than
half of the homicides were women aged 20-29 years (n=53 [64.6%]), non-Hispanic
black women (n=43 [52.4%]), women residing in Cook County (n=47 [57.3%]), and
unmarried women (n=57 [69.5%]). Pregnant and postpartum females aged 10-29 years
were at twice the risk of homicide compared with their nonpregnant or postpartum
counterparts (relative risk 2.20 [95% CI 1.70-2.85]). Non-Hispanic black and
Hispanic females experienced higher rates of homicide than non-Hispanic white
females irrespective of pregnancy or age. CONCLUSION: Although all violence
against women must be addressed, we recommend that state maternal mortality
review committees, in addition to reviewing deaths resulting from obstetric and
clinical causes, should conduct in-depth reviews of pregnancy-associated
homicides and other violent deaths.
PMID- 27500341
TI - Association of Early Amniotomy After Foley Balloon Catheter Ripening and Duration
of Nulliparous Labor Induction.
AB - OBJECTIVE: To evaluate the association between early amniotomy after ripening
with a Foley balloon catheter and duration of labor induction. METHODS: In this
retrospective matched cohort study, 546 nulliparous women with a singleton viable
gestation undergoing cervical ripening with a Foley balloon catheter were
compared based on timing of amniotomy after catheter removal: early (defined as
artificial rupture of membranes less than 1 hour after Foley removal) compared
with no artificial rupture of membranes in the first hour. Women in the early
amniotomy group were matched to women in the control group according to health
care provider type, cervical examination after Foley removal, and indication for
induction in a one-to-one ratio. Bivariable and multivariable analyses were
performed to determine whether early amniotomy was associated with vaginal
delivery within 24 hours and other adverse maternal and neonatal outcomes. Cox
proportional hazard regression was used to compare time intervals from catheter
removal to complete dilation and from catheter removal to delivery. RESULTS: In
univariable analysis, the frequency of vaginal delivery within 24 hours of Foley
placement was higher in women with early amniotomy (42.9% compared with 33.0%,
P=.02). The median time intervals from Foley catheter removal to complete
dilation (9.0 hours compared with 12.1 hours) and to delivery (10.6 hours
compared with 13.8 hours) were also significantly shorter for women who underwent
early amniotomy (P<.001 for both). There were no significant differences in any
other adverse maternal or neonatal outcomes. In multivariable analysis, early
amniotomy remained associated with higher odds of vaginal delivery within 24
hours and shorter times from catheter removal to complete dilation and to
delivery. CONCLUSION: Early amniotomy after Foley balloon catheter removal is
associated with shorter duration of labor induction among nulliparous women.
PMID- 27500342
TI - Smoking Before and During Pregnancy Among Women Reporting Depression or Anxiety.
AB - OBJECTIVE: To describe prepregnancy smoking, prenatal smoking, and prenatal
cessation among women reporting and not reporting depression or anxiety. METHODS:
We analyzed cross-sectional data from the 2009-2011 Pregnancy Risk Assessment
Monitoring System, a population-based survey of women with live births
(N=34,633). Smoking status was defined as self-reported prepregnancy smoking
(during the 3 months before pregnancy), prenatal smoking (during the last 3
months of pregnancy), and prenatal cessation (no smoking by the last 3 months
among prepregnancy smokers). Depression and anxiety status was self-reported of
having either condition or both during the 3 months before pregnancy. We compared
smoking prevalence by self-reported depression and anxiety status using chi tests
and adjusted prevalence ratios. RESULTS: Overall, 16.9% of women in our sample
reported depression, anxiety, or both during the 3 months before pregnancy.
Compared with those who did not report, women who reported depression or anxiety
had significantly higher prepregnancy (46.7% compared with 22.5%, P<.01) and
prenatal smoking (27.5% compared with 10.5%, P<.01). A lower proportion of
prepregnancy smokers who reported depression or anxiety quit smoking by the last
3 months of pregnancy than those who did not report (41.4% compared with 53.8%,
P<.01). In adjusted analyses, women reporting depression or anxiety were 1.5 and
1.7 times more likely to smoke prepregnancy and prenatally, respectively, and
less likely to quit smoking (adjusted prevalence ratio 0.86, 95% confidence
interval 0.80-0.92). CONCLUSION: Women who reported depression, anxiety, or both
were more likely to smoke before and during pregnancy and less likely to quit
smoking during the prenatal period. Screening recommendations for perinatal
depression and anxiety provide an opportunity to identify a subpopulation of
women who may have a higher prevalence of smoking and to provide effective
tobacco cessation interventions and mental health care.
PMID- 27500343
TI - Accuracy of Home-Based Ultrasonographic Diagnosis of Obstetric Risk Factors by
Primary-Level Health Care Workers in Rural Nepal.
AB - OBJECTIVE: To assess the feasibility of ultrasonographic task shifting by
estimating the accuracy at which primary-level health care workers can perform
community-based third-trimester ultrasound diagnosis for selected obstetric risk
factors in rural Nepal. METHODS: Three auxiliary nurse-midwives received two 1
week ultrasound trainings at Tribhuvan University Teaching Hospital in Kathmandu.
At a study site in rural Nepal, pregnant women who were 32 weeks of gestation or
greater were enrolled and received ultrasound examinations from the auxiliary
nurse-midwives during home visits. Each auxiliary nurse-midwife screened for
noncephalic presentation, multiple gestation, and placenta previa. Deidentified
digital ultrasonograms were stored and uploaded onto an online server, where
certified sonologists and ultrasonographers reviewed the images and made their
own diagnoses for the three conditions. Accuracy of auxiliary nurse-midwife
diagnoses was then calculated. RESULTS: A total of 804 women contributed to the
analysis. Each auxiliary nurse-midwife's kappa statistic for diagnosis of
noncephalic presentation was above 0.90 compared with the ultrasonogram
reviewers. Sensitivity, specificity, and positive and negative predictive values
were between 90% and 100% for all auxiliary nurse-midwives. For multiple
gestation, the auxiliary nurse-midwives were in perfect agreement with both the
ultrasonogram reviewers and maternal postpartum self-report. Two placenta previa
cases were detected, and the ultrasonogram reviewers agreed with both.
CONCLUSION: With limited training, primary-level health care workers in rural
Nepal can accurately diagnose selected third-trimester obstetric risk factors
using ultrasonography.
PMID- 27500344
TI - Association of Recorded Estimated Fetal Weight and Cesarean Delivery in Attempted
Vaginal Delivery at Term.
AB - OBJECTIVE: To evaluate the association between documentation of estimated fetal
weight, and its value, with cesarean delivery. METHODS: This was a secondary
analysis of a multicenter observational cohort of 115,502 deliveries from 2008 to
2011. Data were abstracted by trained and certified study personnel. We included
women at 37 weeks of gestation or greater attempting vaginal delivery with live,
nonanomalous, singleton, vertex fetuses and no history of cesarean delivery.
Rates and odds ratios (ORs) were calculated for women with ultrasonography or
clinical estimated fetal weight compared with women without documentation of
estimated fetal weight. Further subgroup analyses were performed for estimated
fetal weight categories (less than 3,500, 3,500-3,999, and 4,000 g or greater)
stratified by diabetic status. Multivariable analyses were performed to adjust
for important potential confounding variables. RESULTS: We included 64,030 women.
Cesarean delivery rates were 18.5% in the ultrasound estimated fetal weight
group, 13.4% in the clinical estimated fetal weight group, and 11.7% in the no
documented estimated fetal weight group (P<.001). After adjustment (including for
birth weight), the adjusted OR of cesarean delivery was 1.44 (95% confidence
interval [CI] 1.31-1.58, P<.001) for women with ultrasound estimated fetal weight
and 1.08 for clinical estimated fetal weight (95% CI 1.01-1.15, P=.017) compared
with women with no documented estimated fetal weight (referent). The highest
estimates of fetal weight conveyed the greatest odds of cesarean delivery. When
ultrasound estimated fetal weight was 4,000 g or greater, the adjusted OR was
2.15 (95% CI 1.55-2.98, P<.001) in women without diabetes and 9.00 (95% CI 3.65
22.17, P<.001) in women with diabetes compared to those with estimated fetal
weight less than 3,500 g. CONCLUSION: In this contemporary cohort of women
attempting vaginal delivery at term, documentation of estimated fetal weight
(obtained clinically or, particularly, by ultrasonography) was associated with
increased odds of cesarean delivery. This relationship was strongest at higher
fetal weight estimates, even after controlling for the effects of birth weight
and other factors associated with increased cesarean delivery risk.
PMID- 27500345
TI - Obstetric Forceps: A Species on the Brink of Extinction.
AB - Both resident training in the use of obstetric forceps and forceps deliveries are
experiencing precipitous declines in the United States. Current minimum training
requirements are insufficient to ensure competency in this skill. These trends
bear striking similarities to observations regarding the decline and ultimate
extinction of biologic species and portend the inevitable disappearance of this
valuable skill from the obstetric armamentarium. Attempts by experienced teaching
faculty to provide residents with experience in a few forceps deliveries are of
little value and may do more harm than good. There would seem to be only two
viable solutions to this dilemma: 1) abandon attempts to teach forceps and
prepare residents for a real-world practice setting in which management of second
stage labor does not include the availability forceps delivery; or 2) prioritize
the development of high-fidelity simulation models in which fetal head size and
attitude and pelvic size and architecture can be continuously varied to allow
residents to obtain sufficient experience to know both how and when to proceed
with forceps delivery. We believe this latter approach is the sole alternative to
inevitable extinction of this species.
PMID- 27500346
TI - Avoiding Inadequate Intrapartum Antibiotic Prophylaxis for Group B Streptococci.
AB - OBJECTIVE: To estimate the frequency and reasons for inadequate group B
streptococci (GBS) prophylaxis at our institution and to estimate what proportion
of cases can be avoided with perfect protocol adherence. METHODS: This was a
retrospective cohort study of neonates born to GBS-colonized women who received
inadequate prophylaxis between April 30, 2013, and May 1, 2014. The maternal
chart was analyzed to categorize each case as avoidable (adequate time on labor
and delivery to receive antibiotics 4 hours before birth and beta-lactam
antibiotic-eligible) or unavoidable and to determine whether a violation of the
2010 Centers for Disease Control and Prevention (CDC) protocol (delayed or
incorrect antibiotics) occurred. RESULTS: A total of 197 of 488 (40.4%, 95%
confidence interval 36.1-44.8%) newborns of group B-colonized women received
inadequate prophylaxis. Of these, 157 cases (79.7%, 73.4-84.8%) were unavoidable
and would have occurred even with perfect protocol adherence. The 40 (20.3%, 15.3
26.5%) avoidable cases due to protocol violations resulted from delayed
antibiotic administration (first dose of antibiotics more than 1 hour after
admission [median 9.33 hours, range 3.83-25 hours] in 25 patients; no antibiotics
in four patients; total 29 patients, 72.5%) or incorrect antibiotic selection (11
patients, 27.5%). CONCLUSIONS: Forty percent of patients received inadequate
prophylaxis, and four of five cases are unavoidable with our current labor
management and the 2010 CDC guidelines. Timeliness and selection of antibiotics
remain areas for improvement, but the overall effects on sepsis prevention will
be modest.
PMID- 27500347
TI - Salpingo-oophorectomy at the Time of Benign Hysterectomy: A Systematic Review.
AB - OBJECTIVE: To compare the long-term risks associated with salpingo-oophorectomy
with ovarian conservation at the time of benign hysterectomy. DATA SOURCES:
MEDLINE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled
Trials were searched from inception to January 30, 2015. We included prospective
and retrospective comparative studies of women with benign hysterectomy who had
either bilateral salpingo-oophorectomy (BSO) or conservation of one or both
ovaries. METHODS OF STUDY SELECTION: Reviewers double-screened 5,568 citations
and extracted eligible studies into customized forms. Twenty-six comparative
studies met inclusion criteria. Studies were assessed for results, quality, and
strength of evidence. TABULATION, INTEGRATION, AND RESULTS: Studies were
extracted for participant, intervention, comparator, and outcomes data. When
compared with hysterectomy with BSO, prevalence of reoperation and ovarian cancer
was higher in women with ovarian conservation (ovarian cancer risk of 0.14-0.7%
compared with 0.02-0.04% among those with BSO). Hysterectomy with BSO was
associated with a lower incidence of breast and total cancer, but no difference
in the incidence of cancer mortality was found when compared with ovarian
conservation. All-cause mortality was higher in women younger than age 45 years
at the time of BSO who were not treated with estrogen replacement therapy (hazard
ratio [HR] 1.41, 95% confidence interval [CI] 1.04-1.92). Coronary heart disease
(HR 1.26, 95% CI 1.04-1.54) and cardiovascular death were higher among women with
BSO (HR 1.84, 95% CI 1.27-2.68), especially women younger than 45 years who were
not treated with estrogen. Finally, there was an increase in the prevalence of
dementia and Parkinson disease among women with BSO compared with conservation,
especially in women younger than age 50 years. Clinical practice guidelines were
devised based on these results. CONCLUSION: Bilateral salpingo-oophorectomy
offers the advantage of effectively eliminating the risk of ovarian cancer and
reoperation but can be detrimental to other aspects of health, especially among
women younger than age 45 years.
PMID- 27500348
TI - Group Prenatal Care Compared With Traditional Prenatal Care: A Systematic Review
and Meta-analysis.
AB - OBJECTIVE: To estimate the effect of group prenatal care on perinatal outcomes
compared with traditional prenatal care. DATA SOURCES: We searched MEDLINE
through PubMed, EMBASE, Scopus, Cumulative Index of Nursing and Allied Health
literature, the Cochrane Database of Systematic Reviews, the Database of
Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled
Trials, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We searched
electronic databases for randomized controlled trials and observational studies
comparing group care with traditional prenatal care. The primary outcome was
preterm birth. Secondary outcomes were low birth weight, neonatal intensive care
unit admission, and breastfeeding initiation. Heterogeneity was assessed using
the Q test and I statistic. Pooled relative risks (RRs) and weighted mean
differences were calculated using random-effects models. TABULATIONS,
INTEGRATION, AND RESULTS: Four randomized controlled trials and 10 observational
studies met inclusion criteria. The rate of preterm birth was not significantly
different with group care compared with traditional care (11 studies: pooled
rates 7.9% compared with 9.3%, pooled RR 0.87, 95% confidence interval [CI] 0.70
1.09). Group care was associated with a decreased rate of low birth weight
overall (nine studies: pooled rate 7.5% group care compared with 9.5% traditional
care; pooled RR 0.81, 95% CI 0.69-0.96), but not among randomized controlled
trials (four studies: 7.9% group care compared with 8.7% traditional care, pooled
RR 0.92, 95% CI 0.73-1.16). There were no significant differences in neonatal
intensive care unit admission or breastfeeding initiation. CONCLUSION: Available
data suggest that women who participate in group care have similar rates of
preterm birth, neonatal intensive care unit admission, and breastfeeding.
PMID- 27500349
TI - Risk Factors for Dyspareunia After First Childbirth.
AB - OBJECTIVE: To investigate risk factors for dyspareunia among primiparous women.
METHODS: This was a planned secondary analysis using data from the 1- and 6-month
postpartum interviews of a prospective study of women who delivered their first
neonate in Pennsylvania, 2009-2011. Participants who had resumed sexual
intercourse by the 6-month interview (N=2,748) constituted the analytic sample.
Women reporting a big or medium problem with painful intercourse at 6 months were
categorized as having dyspareunia. Multivariable logistic regression was used to
evaluate the effect of patient characteristics, obstetric and psychosocial
factors, and breastfeeding on dyspareunia. RESULTS: There were 583 women (21.2%)
who reported dyspareunia at 6 months postpartum. Nearly one third of those
breastfeeding at 6 months reported dyspareunia (31.5%) compared with 12.7% of
those not breastfeeding (adjusted odds ratio [OR] 2.89, 95% confidence interval
[CI] 2.33-3.59, P<.001); 32.5% of those reporting a big or medium problem with
perineal pain at 1 month reported dyspareunia at 6 months compared with 15.9% of
those who did not (adjusted OR 2.45, 95% CI 1.93-3.10, P<.001); 28.3% of women
who reported fatigue all or most of the time at 1 month reported dyspareunia at 6
months compared with 18.0% of those who reported fatigue less often (adjusted OR
1.60, 95% CI 1.30-1.98, P<.001); and 24.1% of those who scored in the upper third
on the stress scale at 1 month reported dyspareunia at 6 months postpartum
compared with 15.6% of those who scored in the lowest third (adjusted OR 1.55,
95% CI 1.18-2.02, P=.001). CONCLUSION: In this prospective cohort study, we
identified specific risk factors for dyspareunia in primiparous women that can be
discussed at the first postpartum visit, including breastfeeding, perineal pain,
fatigue, and stress.
PMID- 27500350
TI - Association of a Biweekly Research Workgroup With Enhanced Resident Research
Productivity.
AB - Almost all residency programs require a resident research project, yet teaching
and mentoring of the required skills are often lacking. We established an every
other-week gynecologic oncology research workgroup at our institution for
obstetrics and gynecology faculty, fellows, and residents with the goal of
increasing resident research education, involvement, and productivity. An
informal, discussion-style format was adopted as a forum for brainstorming
research ideas, formulating study protocols, and collaborating on institutional
review board submissions. Additional aims included editorial feedback on
abstracts and manuscripts as well as oral presentation preparation. The academic
productivity of trainees mentored by the gynecologic oncology division was
queried for 27 months before and 27 months after workgroup initiation,
specifically assessing resident involvement in institutional review board
submission, abstract presentation, and manuscript preparation. Institution of our
workgroup was associated with a dramatic increase in resident research output,
including manuscript preparation and presentations at national meetings. We
describe our experience because it may benefit other residency programs wishing
to improve both resident research education and productivity.
PMID- 27500351
TI - Self-Administered Lidocaine Gel for Intrauterine Device Insertion in Nulliparous
Women: A Randomized Controlled Trial.
AB - OBJECTIVE: To evaluate self-administration of vaginal lidocaine gel to decrease
pain with intrauterine device (IUD) insertion in nulliparous women. METHODS: In
this randomized, double-blind, placebo-controlled trial, women self-administered
2% lidocaine or placebo vaginal gel 5 minutes before IUD insertion. The primary
outcome was change in pain from baseline to IUD insertion on a 100-mm visual
analog scale. We also assessed pain after speculum insertion, tenaculum
placement, uterine sounding, and 5 minutes after IUD insertion. Secondary
outcomes included patient acceptability, ease of IUD insertion, and need for pain
medication for up to 7 days. RESULTS: From July 2012 to May 2013, 59 women were
randomized; 30 received lidocaine gel and 29 placebo. Baseline demographics,
including age, race, and body mass index, were similar. There was no difference
in median change in pain during IUD insertion in women receiving lidocaine (61 mm
[interquartile range 53-71]) compared with placebo (69 mm [interquartile range 63
80], P=.06). Women receiving lidocaine experienced less pain with tenaculum
placement (32 mm [interquartile range 18-54]) compared with placebo (56 mm
[interquartile range 26-75], P=.02). Most (76%) women were satisfied with their
IUD insertion experience and 86% would probably or definitely recommend an IUD to
a friend. Thirty-four percent of women required pain medication for at least 3
days after IUD insertion. CONCLUSION: For nulliparous women, self-administered
vaginal lidocaine gel does not reduce pain with IUD insertion, but does decrease
pain with tenaculum placement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,
http://clinicaltrials.gov, NCT01534520.
PMID- 27500352
TI - Accuracy of Onsite Tests to Detect Asymptomatic Bacteriuria in Pregnancy: A
Systematic Review and Meta-analysis.
AB - OBJECTIVE: To estimate the accuracy of onsite tests to detect asymptomatic
bacteriuria among pregnant women. DATA SOURCES: We searched MEDLINE, EMBASE, Web
of Science, Scopus, and Latin-American Literature from inception until June 2015
without language restrictions. The ClinicalTrials.gov register database was
screened to identify any recently completed studies. METHODS OF STUDY SELECTION:
Two independent reviewers selected studies that recruited asymptomatic pregnant
women to evaluate the accuracy of onsite tests in detecting the presence of
bacteria in the urine using urine culture as a reference standard. TABULATION,
INTEGRATION, AND RESULTS: Women's characteristics, study design, urine sample
collection, and handling were extracted along with the test accuracy data. Where
possible, we pooled the data using a bivariate, hierarchical random-effects
model. Of 1,360 screened references, 27 articles (13,641 women) with test
accuracy data on nine tests met the inclusion criteria. The most commonly
evaluated test was urine dipstick. The pooled sensitivity and specificity of
nitrites detected by dipstick to detect asymptomatic bacteriuria were 0.55 (95%
confidence interval [CI] 0.42-0.67) and 0.99 (95% CI 0.98-0.99), respectively.
The Griess test to detect nitrites had a sensitivity of 0.65 (95% CI 0.50-0.78)
and specificity of 0.99 (95% CI 0.98-1.00). Dipslide with Gram staining had a
pooled sensitivity of 0.86 (95% CI 0.80-0.91) and specificity of 0.97 (95% CI
0.93-0.99). CONCLUSION: The specificity of onsite tests is high; however, the
sensitivity is not with the result that they will fail to detect a substantial
number of cases of asymptomatic bacteriuria. CLINICAL TRIAL REGISTRATION:
PROSPERO International prospective register of systematic reviews,
http://www.crd.york.ac.uk/PROSPERO/, CRD42015027905.
PMID- 27500353
TI - Optimal Lentivirus Production and Cell Culture Conditions Necessary to
Successfully Transduce Primary Human Bronchial Epithelial Cells.
AB - In vitro culture of primary human bronchial epithelial (HBE) cells using air
liquid interface conditions provides a useful model to study the processes of
airway cell differentiation and function. In the past few years, the use of
lentiviral vectors for transgene delivery became common practice. While there are
reports of transduction of fully differentiated airway epithelial cells with
certain non-HIV pseudo-typed lentiviruses, the overall transduction efficiency is
usually less than 15%. The protocol presented here provides a reliable and
efficient method to produce lentiviruses and to transduce primary human bronchial
epithelial cells. Using undifferentiated bronchial epithelial cells, transduction
in bronchial epithelial growth media, while the cells attach, with a multiplicity
of infection factor of 4 provides efficiencies close to 100%. This protocol
describes, step-by-step, the preparation and concentration of high-titer
lentiviral vectors and the transduction process. It discusses the experiments
that determined the optimal culture conditions to achieve highly efficient
transductions of primary human bronchial epithelial cells.
PMID- 27500354
TI - FRET Imaging in Three-dimensional Hydrogels.
AB - Imaging of Forster resonance energy transfer (FRET) is a powerful tool for
examining cell biology in real-time. Studies utilizing FRET commonly employ two
dimensional (2D) culture, which does not mimic the three-dimensional (3D)
cellular microenvironment. A method to perform quenched emission FRET imaging
using conventional widefield epifluorescence microscopy of cells within a 3D
hydrogel environment is presented. Here an analysis method for ratiometric FRET
probes that yields linear ratios over the probe activation range is described.
Measurement of intracellular cyclic adenosine monophosphate (cAMP) levels is
demonstrated in chondrocytes under forskolin stimulation using a probe for EPAC1
activation (ICUE1) and the ability to detect differences in cAMP signaling
dependent on hydrogel material type, herein a photocrosslinking hydrogel (PC-gel,
polyethylene glycol dimethacrylate) and a thermoresponsive hydrogel (TR-gel).
Compared with 2D FRET methods, this method requires little additional work.
Laboratories already utilizing FRET imaging in 2D can easily adopt this method to
perform cellular studies in a 3D microenvironment. It can further be applied to
high throughput drug screening in engineered 3D microtissues. Additionally, it is
compatible with other forms of FRET imaging, such as anisotropy measurement and
fluorescence lifetime imaging (FLIM), and with advanced microscopy platforms
using confocal, pulsed, or modulated illumination.
PMID- 27500355
TI - The Default Dilemma: Code Status Regardless of Medical Context.
PMID- 27500356
TI - Probable glucometer interference caused by topical iodine solution test site
preparation.
AB - WHAT IS KNOWN AND OBJECTIVE: Use of disinfectants, such as alcohol prep pads, for
test site preparation have demonstrated alterations in glucose readings. One case
report details an overestimation of blood glucose (BG) readings when using
Chemstrip bG and Visidex reagent test strips after cleaning test site with
povidone-iodine swabs CASE SUMMARY: We present a case of a clinically relevant
probable drug-device interaction between topical iodine and a point-of-care
glucometer in a 28 year old pregnant woman of Chinese descent. In this case, the
use of 10% povidone-iodine solution on the testing site before lancing likely
resulted in variable and inaccurate BG readings, which was not reproduced when
the patient used hand washing instead of iodine. WHAT IS NEW AND CONCLUSION: Our
report expands on this prior knowledge by demonstrating that such an alteration
associated with iodine can occur with modern electrochemical glucometers. In
patients that have aberrant or variable BG readings, providers should investigate
for improper testing technique.
PMID- 27500357
TI - Hypoxia induces copper stable isotope fractionation in hepatocellular carcinoma,
in a HIF-independent manner.
AB - Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer,
with increasing incidence worldwide. The unrestrained proliferation of tumour
cells leads to tumour hypoxia which in turn promotes cancer aggressiveness. While
changes in the concentration of copper (Cu) have long been observed upon
cancerization, we have recently reported that the isotopic composition of copper
is also altered in several types of cancer. In particular, we showed that in
hepatocellular carcinoma, tumour tissue contains heavier copper compared to the
surrounding parenchyma. However, the reasons behind such isotopic signature
remained elusive. Here we show that hypoxia causes heavy copper enrichment in
several human cell lines. We also demonstrate that this effect of hypoxia is pH,
HIF-1 and -2 independent. Our data identify a previously unrecognized cellular
process associated with hypoxia, and suggests that in vivo tumour hypoxia
determines copper isotope fractionation in HCC and other solid cancers.
PMID- 27500358
TI - Loaded Ce-Ag organic-inorganic hybrids and their antibacterial activity.
AB - There are requirements for surfaces with antibacterial properties in various
technological fields. U-PEO hybrids with antibacterial properties were
synthesized by the sol-gel process, incorporating combinations of cerium and
silver salts at different silver molar fractions (0, 0.02, 0.05, 0.10, and 1)
relative to the total amount of doped cations. The loaded hybrids were
characterized by TGA, XRD, and Raman spectroscopy. Release tests were performed
using UV-vis spectroscopy, and the antibacterial properties of the hybrids were
studied in agar tests and turbidimetry assays. The nanostructural evolution of
the hybrids during the release of the antibacterial agents was investigated by in
situ SAXS. XRD results showed the presence of the AgCl crystalline phase in the
loaded hybrids from a silver molar fraction of 0.05. Raman spectroscopy evidenced
the interaction of silver cations with the polymeric part of the hybrid. SAXS
results confirmed these interactions and showed that cerium species interacted
with both organic and inorganic parts of the hybrids. The loaded U-PEO hybrids
were found to release all the incorporated cerium in 1h, while the hybrid
containing 100% of silver released only 78% of the incorporated silver. All the
loaded hybrids displayed antibacterial activity against the Pseudomonas
aeruginosa bacterium. The antibacterial activity was found to increase with
silver molar fraction. Due to its high antibacterial activity and low silver
molar fraction, the loaded hybrid with silver molar fraction of 0.10 seemed to be
a good compromise between efficiency, esthetic transparency, and photostability.
PMID- 27500359
TI - Multi-functional vesicles for cancer therapy: The ultimate magic bullet.
AB - Delivering chemotherapy specifically, effectively and safely to tumor remains a
significant challenge in recent years. Although cancer cells are more vulnerable
than normal to the effect of anticancer agents, these drugs are non-selective and
can cause injury to normal tissues. Different approaches i.e. passive, active and
magnetic targeting, smart devices with appropriate stimuli-sensitive properties
or drugs combinations, have been already proposed as single methods, contributing
to minimize severe side effects and enhancing tumor-targeting efficacy. Often,
the use of a single strategy is not sufficient, whereby multi-functional approach
has been suggested as further evolution of traditional "magic bullet" proposed in
the early 1900s by Paul Ehrlich. Among the macromolecular systems useful for
targeted drug delivery, liposomes and niosomes are the most extensively studied
and they own the most suitable characteristics to be converted in multi
functional devices. Liposomes and niosomes are nanovesicles that contain
amphiphilic molecules arranged in concentric bilayers, delimitating an aqueous
core. These vesicular carriers are very versatile, since they can be differently
designed and modified in such a way that they exhibit combinations of the
following properties: longevity in blood, specific target to the tumor, respond
to internal/external stimuli, promotion of drug intracellular delivery. This
review will focus on the potential of multi-functional vesicular nanocarriers in
cancer therapy, analizing each combination of targeting strategies, stimuli
sensitivity and drug combinations and giving an exhaustive collection of recent
investigations. Many multi-functional vesicular devices have shown great promise
in clinical application, indicating broad potential as therapeutics in the near
future, but more needs to be done. The development of more specific and efficient
carriers for a personalized cancer therapy is the next challenge.
PMID- 27500360
TI - Substrate-mediated delivery of gene complex nanoparticles via polydopamine
coating for enhancing competitiveness of endothelial cells.
AB - Substrate-mediated delivery of functional plasmid DNA (pDNA) has been proven to
be a promising strategy to promote competitiveness of endothelial cells (ECs)
over smooth muscle cells (SMCs), which is beneficial to inducing fast
endothelialization of implanted vascular devices. Thus, it is of great importance
to develop universal approaches with simplicity and easiness to immobilize DNA
complex nanoparticles on substrates. In this study, the bioinspired polydopamine
(PDA) coating was employed in immobilization of DNA complex nanoparticles, which
were composed of protamine (PrS) and plasmid DNA encoding with hepatocyte growth
factor (HGF-pDNA) gene. We demonstrated that the DNA complex nanoparticles can be
successfully immobilized onto the PDA surface. Consequently, the HGF expression
of both ECs and SMCs were significantly improved when they cultured on the DNA
complex nanoparticles-immobilized substrates. Furthermore, EC proliferation was
specifically promoted due to bioactivity of HGF, leading to an enhancement of EC
competitiveness over SMCs. Our findings demonstrated the substrate-mediated
functional gene nanoparticle delivery through PDA coating as a simple and
efficient approach. It may hold great potential in the field of interventional
cardiovascular implants.
PMID- 27500361
TI - The Long-Term Follow-up and Support for Living Organ Donors: A Center-Based
Initiative Founded on Developing a Community of Living Donors.
AB - Transplant professionals recognize that the long-term follow-up of living organ
donors is a priority, yet there has been no implemented solution to this problem.
This critical gap is essential, because the transplant field is now emphasizing
living donation as a means to address the organ shortage. We detail our living
donor initiative, which sets several priorities we recognize as fundamental to
persons who have donated organs at our transplant center. This intervention
attempts to mitigate the donor and center factors that are known to contribute to
the lack of long-term follow-up. Beyond that, our goals are aimed at providing
ongoing engagement, wellness, clinical data accrual, laboratory follow-up, and
social support for our living donors, in continuity. Our ultimate goal is to
nurture the development of local living donor community networks by providing
social engagement for current and past donors, which also serves as a platform
for greater population education on the societal importance of living donation.
This initiative is based on joint recognition by our transplant team and our
hospital leadership that supporting the long-term welfare of living donors is
essential to accomplishing the goal of expanding living donor transplantation.
The transplant team and hospital missions are aligned, and both contribute
resources to the initiative.
PMID- 27500362
TI - Prevention of Heat Stress Adverse Effects in Rats by Bacillus subtilis Strain.
AB - This study was designed to evaluate the protective effect of the Bacillus
subtilis strain against complications related to heat stress. Thirty-two Sprague
Dawley rats were used in this study. Animals were orally treated twice a day for
two days with B. subtilis BSB3 strain or PBS. The next day after the last
treatment, each group was divided and two experimental groups (one treated with
PBS and one treated with B. subtilis) were placed at 45 (o)C for 25 min. Two
control groups stayed for 25 min at room temperature. All rats were euthanized
and different parameters were analyzed in all groups. Adverse effects of heat
stress are registered by the decrease of villi height and total mucosal thickness
in the intestinal epithelium; translocation of bacteria from the lumen; increased
vesiculation of erythrocytes and elevation of the lipopolysaccharides (LPS) level
in the blood. The protective efficacy of treatment is evaluated by prevention of
these side effects. The protocol was set up for the oral treatment of rats with
bacteria for prevention of heat stress complications, but this protocol can be
modified and used for other routes of administration and for analysis of
different compounds.
PMID- 27500363
TI - Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs.
AB - The intraocular route of drug administration enables the delivery of high
concentrations of therapeutic drugs, while minimizing their systemic absorption.
Several drugs are administered into the anterior chamber or vitreous, and the
intraocular injection has been effective in curing various intraocular diseases.
Rabbit eyes have been widely used for ophthalmic research, as the animal is easy
to handle and economical compared to other mammals, and the size of a rabbit eye
is similar to that of a human eye. Using a 30 G needle, drugs can be injected
into the intracameral and intravitreal spaces of rabbit eyes. The eyeballs are
then frozen until analysis, and can be divided into the aqueous humor, vitreous,
and retina/choroid. The vitreous and retina/choroid samples can be homogenized
and solubilized before analysis. Then, immunoassays can be performed to measure
the concentrations of intraocular drugs in each compartment. Appropriate
pharmacokinetic models can be used to calculate several parameters, such as the
half-life and maximum concentration of the drug. Rabbit eyes can be a good model
for pharmacokinetic studies of intraocular drugs.
PMID- 27500364
TI - Compartmentalized dynamics of cytomegalovirus replication in treated congenital
infection.
AB - BACKGROUND: Cytomegalovirus (CMV) is the most prevalent congenital infection in
developed countries. A significant number of infected infants develop long-term
neurodevelopmental and hearing impairment irrespective of whether disease is
detectable at birth. Studies of viral load and replication dynamics have informed
the treatment of CMV in adult populations but no similar data exist in neonates.
OBJECTIVES: To study CMV virus kinetics in different body fluids of babies
treated for congenital infection. STUDY DESIGN: CMV virus load was sequentially
analyzed in blood, urine and saliva in 17 babies treated for symptomatic
congenital CMV infection. RESULTS: Virus was detectable in the urine and saliva
of all babies at baseline but in only 15/17 in blood. At the end of 6 weeks of
antiviral treatment CMV remained detectable in 9/14 blood samples, 9/12 urine
samples and 4/7 salivary swabs. Median half-life (T1/2) of virus decline in blood
was 2.4 days (IQR 1.9-3.3) and basic reproductive number (Ro) was 2.3. Although
T1/2 values were similar in urine and saliva to those observed in blood, virus
dynamics differed both during and after treatment. CONCLUSIONS: T1/2 and Ro in
blood in this group of neonates were similar to values derived from studies of
immunocompromised adults. The persistent viremia observed in treated neonates
cannot therefore be adequately explained by the virus dynamics early in
treatment. The different dynamics exhibited in blood and urine suggests that
studying changes in distinct body compartments may assist in further
understanding long-term manifestations of disease.
PMID- 27500365
TI - Beta-HPV types in patients with head and neck pathology and in healthy subjects.
AB - BACKGROUND: Human papillomaviruses (HPV) are a heterogeneous group of viruses
classified into five genera. The beta-HPV type (beta-PV) infection is very common
but mostly asymptomatic in immunocompetent individuals. However, beta-PVs play a
role in Epidermodysplasia verruciformis and possibly in non-melanoma skin cancer.
Head and neck cancer (HNC) is a common cancer type worldwide and high-risk alpha
PV involvement in HNC has been extensively studied but beta-PV types have rarely
been the focus of such studies. OBJECTIVES: To evaluate the prevalence of beta-PV
types in HNC, subjects with non-malignant or potentially pre-malignant oral
lesions, and healthy controls. STUDY DESIGN: The frequency of different beta-PVs
in samples from oral (n=35) and oropharyngeal (n=35) cancer patients, gender- and
age-matched healthy controls (n=70), and subjects with various non-malignant or
potentially pre-malignant oral lesions (n=102) was assessed by a highly
sensitive, bead-based, multiplex genotyping assay. RESULTS: Overall, 54.8% of all
tested samples contained at least one beta-PV type. Even though the correlation
between types found in lavage and tissue specimens from cancer patients was low,
there was a large statistically significant difference between oropharyngeal
cancer patients and matched controls for HPV5 (P=0.003; OR=15.58) and between
both oral (P=0.026; OR=5.7) and oropharyngeal cancer patients (P=0.002; OR=25.5)
and controls for HPV122. In addition, there was no correlation between the
prevalence of alpha and beta-PVs in the study patients. CONCLUSION: The study
provides new data on the prevalence of beta-PVs in HNC. HPV5 was found
significantly associated with HNC as already observed by other studies.
Additionally, the significant association of HPV122 with HNC might warrant
further study as this type has not been extensively studied so far.
PMID- 27500366
TI - Coronary stent thrombosis: what have we learned?
PMID- 27500367
TI - Effect of appendicectomy on colonic inflammation and neoplasia in experimental
ulcerative colitis.
AB - BACKGROUND: Ulcerative colitis (UC) promotes cancer, and can be ameliorated by
early appendicectomy for appendicitis. The aim of the study was to explore the
effect of appendicectomy on colitis and colonic neoplasia in an animal model of
colitis and a cohort of patients with UC. METHODS: Five-week old IL10/Nox1(DKO)
mice with nascent colitis and 8-week-old IL10/Nox1(DKO) mice with established
colitis underwent appendicectomy (for experimental appendicitis or no
appendicitis) or sham laparotomy. The severity and extent of colitis was assessed
by histopathological examination, and a clinical disease activity score was
given. From a cohort of consecutive patients with UC who underwent colectomy, the
prevalence of appendicectomy and pathological findings were collected from two
institutional databases. RESULTS: Appendicectomy for appendicitis ameliorated
experimental colitis in the mice; the effect was more pronounced in the 5-week
old animals. Appendicectomy in the no-appendicitis group was associated with an
increased rate of colonic high-grade dysplasia (HGD) or cancer compared with
rates in sham and appendicitis groups (13 of 20 versus 0 of 20 and 0 of 20
respectively; P < 0.001). Fifteen of 232 patients who underwent colectomy for UC
had previously had an appendicectomy, and nine of these had colonic cancer or
HGD. Thirty (13.8 per cent) of 217 patients with the appendix in situ had colonic
neoplastic lesions. Multivariable analysis showed that previous appendicectomy
was associated with colorectal neoplasia (odds ratio 16.88, 95 per cent c.i. 3.32
to 112.69). CONCLUSION: Appendicectomy for experimental appendicitis ameliorated
colitis. The risk of colorectal neoplasia appeared to increase following
appendicectomy without induced appendicitis in a mouse model of colitis, and in
patients with UC who had undergone appendicectomy. Surgical relevance
Appendicectomy for appendicitis protects against UC. In this murine model of
colitis, appendicectomy for experimental appendicitis protected against colitis,
but appendicectomy without appendicitis promoted colorectal carcinogenesis. In
patients with ulcerative colitis who underwent colectomy, absence of the appendix
(proof of previous appendicectomy) in the resection specimen was independently
associated with colorectal neoplasia. Although patients with UC and a history of
appendicectomy represent a small subset, they may need closer monitoring for
colorectal neoplasia.
PMID- 27500368
TI - Honorary and ghost authorship in reports of randomised clinical trials in
oncology.
AB - BACKGROUND: The International Committee of Medical Journal Editors (ICMJE) has
developed guidelines for responsible and accountable authorship. Few studies have
assessed the frequency and nature of ghost and honorary authorship in
publications of oncology trials. MATERIALS AND METHODS: Reports of randomised
clinical trials evaluating systemic cancer therapy published from July 2010 to
December 2012 in six high-impact journals were identified systematically. Ghost
authorship was determined to be present in any scenario where investigators or
statisticians listed in the protocol were not included as authors and not
acknowledged in the report of the trial. The list of contributions for authors of
published articles was recorded, and we defined an article as having an honorary
author if any author did not meet all three criteria established by ICMJE in
1985. RESULTS: Two hundred publications were identified. For 61 articles,
protocols with listed investigators were available, and 40 (66%) of these
articles met our definition of ghost authorship. Medical writers were involved in
89 articles (45%), and assistance was acknowledged only in sponsored trials.
Contributions of each author were provided in 195 articles, and 63 (33%) articles
met our definition for honorary authorship. Funding source was not a predictor
for either honorary or ghost authorship. Journal impact factor was positively
associated with honorary authorship (odds ratio = 1.03; 95% confidence interval =
1.004-1.065; P = 0.03), but not with ghost authorship. CONCLUSION: Ghost and
honorary authorship are prevalent in articles describing trials for systemic
therapy of cancer. Guidelines should be enforced to improve transparency and
accountability.
PMID- 27500369
TI - International normalized ratio testing with a point-of-care coagulometer in 1
month-old infants: A comparison with Normotest.
AB - INTRODUCTION: Early infants are at risk of vitamin K (VK) deficiency-associated
bleeding unless they receive VK prophylaxis. A coagulation screening test might
be necessary to detect prophylactic failure, but it is rarely conducted owing to
the difficulty of blood sampling. CoaguChek XS is a portable, point-of-care (POC)
coagulation analyzer that determines international normalized ratios (INRs) using
only small volumes of blood. Although POC tests assessing INR have become
widespread for adults, studies have not been performed in early infancy. This
study aimed to determine the reference interval (RI) for INR for 1-month-old
infants using the CoaguChek XS and to compare INRs with Normotest (NT) values to
evaluate its efficacy as a VK deficiency screening test. MATERIALS AND METHODS:
This study included 578 consecutive 1-month-old, healthy, term infants who
underwent a 1-month health checkup. CoaguChek XS INRs and NT values were analyzed
for each subject. RESULTS: The enrolled neonates were orally administered VK 6
12h and 4days after birth. An INR RI for 1-month-old infants was established
using the CoaguChek XS (range of 0.9-1.1). On the other hand, the NT RI was 69%
130%. We observed a significant inverse correlation between INRs and NT values.
CONCLUSIONS: Our study is the first to establish an INR RI using the CoaguChek XS
for 1-month-old, healthy, term infants. CoaguChek XS INR was more convenient to
test than NT. However, we could not demonstrate its efficacy as a VK deficiency
screening test because no infant had an aberrant NT value or a bleeding disorder.
PMID- 27500370
TI - Changes in hydration of the stratum corneum are the most suitable indicator to
evaluate the irritation of surfactants on the skin.
AB - BACKGROUND/PURPOSE: Irritancy levels of surfactants on human skin have not been
clarified completely. The relationships between skin damage and changes of skin
properties caused by various surfactants were investigated using non-invasive
measurements. METHODS: Aqueous solutions of seven kinds of anionic, non-ionic,
and amphoteric surfactants were exposed to the inside of forearm skin of 20 human
subjects in two separate studies using the cup method. Hydration of the stratum
corneum (SC), transepidermal water loss (TEWL), pH, skin surface roughness, and
contents of the SC were measured before and after one exposure and after five and
nine consecutive exposures to various surfactants. The discontinuation ratio of
subjects for testing in each surfactant was determined by skin irritation
symptoms and was defined as the degree of skin damage. RESULTS: Significant
changes were observed only in hydration, TEWL, and natural moisturizing factors
(NMF) content in the SC following surfactant exposure. A significant correlation
was observed between the discontinuation ratio of each surfactant and the changes
of hydration, TEWL, and NMF. Especially, the change of SC hydration showed an
excellent correlation with the discontinuation ratio both for single (r = 0.942,
P < 0.001) and for chronic exposures (r = 0.934, P < 0.001). CONCLUSION: Our
results indicate that the change of hydration of the SC is equivalent to the skin
damage caused by surfactants, and therefore is the most suitable indicator to
evaluate the irritation of surfactants on the skin.
PMID- 27500371
TI - Perspectives on Promoting Hospital Primary Vaginal Birth: A Qualitative Study.
AB - BACKGROUND: One in three women will deliver by cesarean, a procedure that can be
life saving, but which also carries short- and long-term risks. There is growing
interest in preventing primary cesarean deliveries, while optimizing the health
of the mother and infant. The primary aim of this study was to use participatory
action strategies and ethnographic interview data collected from diverse
stakeholders in birth (caregivers, women, policymakers) about facilitators and
barriers to the achievement of primary vaginal birth in first-time mothers in
hospital settings. The secondary aim was to use the findings to identify
strategies to promote primary vaginal birth and future areas of research.
METHODS: Individual and small group interviews were conducted with caregivers and
policymakers (N = 79) and first-time mothers (N = 24) at a northeastern hospital.
All interviews were audio-recorded, transcribed, and analyzed using Atlas.ti.
RESULTS: Four broad themes were identified: 1) preparation for childbirth, 2)
early labor management, 3) caregiver knowledge and practice style, and 4) birth
environment (physical, cultural/emotional). The first two were closely linked
from caregivers' perspectives. If the woman was not prepared for childbirth, it
was perceived she would be more likely to present to the hospital in early labor.
Once there, it was hard to prevent admission and interventions. A woman's
knowledge and confidence were perceived as powerful mediators for vaginal birth.
CONCLUSION: Caregivers and first-time mothers identified early labor management
and childbirth preparation as important factors to promote primary vaginal birth
in hospital settings. Both deserve further inquiry as potential strategies to
decrease rising cesarean delivery rates.
PMID- 27500372
TI - Spatial and temporal variation in artisanal catches of dolphinfish Coryphaena
hippurus off north-eastern Brazil.
AB - The sampling of fish from the artisanal fleet operating with surface lines off
north-eastern Brazil was carried out between 1998 and 2000. Generalized linear
models (GLMs) were used to standardize mean abundance indices using catch and
fishing effort data on dolphinfish Coryphaena hippurus and to identify abundance
trends in time and space, using 1215 surface line deployments. A standard
relative abundance index (catch per unit effort, CPUE) was estimated for the most
frequent vessels used in the sets, employing factors and coefficients generated
in the GLMs. According to the models, C. hippurus catches are affected by the
operating characteristics and power of different fishing vessels. These
differences highlight the need for standardization of catch and effort data for
artisanal fisheries. The highest mean abundance values for C. hippurus were off
the state of Rio Grande do Norte, with an increasing tendency in areas with
greater depths and more distant from the coast, reaching maximal values in areas
whose depths range from 200 to 500 m. The highest mean abundance values occurred
between April and June. The higher estimated abundance of C. hippurus in this
period off the state of Rio Grande do Norte and within the 200-500 m depth range
may be related to a migration pattern of food sources, as its main prey, the
flying fish Hirundichthys affinis, uses floating algae as refuge and to deposit
its pelagic eggs.
PMID- 27500374
TI - Rearing the Fruit Fly Drosophila melanogaster Under Axenic and Gnotobiotic
Conditions.
AB - The influence of microbes on myriad animal traits and behaviors has been
increasingly recognized in recent years. The fruit fly Drosophila melanogaster is
a model for understanding microbial interactions with animal hosts, facilitated
by approaches to rear large sample sizes of Drosophila under microorganism-free
(axenic) conditions, or with defined microbial communities (gnotobiotic). This
work outlines a method for collection of Drosophila embryos, hypochlorite
dechorionation and sterilization, and transfer to sterile diet. Sterilized
embryos are transferred to sterile diet in 50 ml centrifuge tubes, and developing
larvae and adults remain free of any exogenous microbes until the vials are
opened. Alternatively, flies with a defined microbiota can be reared by
inoculating sterile diet and embryos with microbial species of interest. We
describe the introduction of 4 bacterial species to establish a representative
gnotobiotic microbiota in Drosophila. Finally, we describe approaches for
confirming bacterial community composition, including testing if axenic
Drosophila remain bacteria-free into adulthood.
PMID- 27500375
TI - Observation of Enhanced Hole Extraction in Br Concentration Gradient Perovskite
Materials.
AB - Enhancing hole extraction inside the perovskite layer is the key factor for
boosting photovoltaic performance. Realization of halide concentration gradient
perovskite materials has been expected to exhibit rapid hole extraction due to
the precise bandgap tuning. Moreover, a formation of Br-rich region on the tri
iodide perovskite layer is expected to enhance moisture stability without a loss
of current density. However, conventional synthetic techniques of perovskite
materials such as the solution process have not achieved the realization of
halide concentration gradient perovskite materials. In this report, we
demonstrate the fabrication of Br concentration gradient mixed halide perovskite
materials using a novel and facile halide conversion method based on vaporized
hydrobromic acid. Accelerated hole extraction and enhanced lifetime due to Br
gradient was verified by observing photoluminescence properties. Through the
combination of secondary ion mass spectroscopy and transmission electron
microscopy with energy-dispersive X-ray spectroscopy analysis, the diffusion
behavior of Br ions in perovskite materials was investigated. The Br-gradient was
found to be eventually converted into a homogeneous mixed halide layer after
undergoing an intermixing process. Br-substituted perovskite solar cells
exhibited a power conversion efficiency of 18.94% due to an increase in open
circuit voltage from 1.08 to 1.11 V and an advance in fill-factor from 0.71 to
0.74. Long-term stability was also dramatically enhanced after the conversion
process, i.e., the power conversion efficiency of the post-treated device has
remained over 97% of the initial value under high humid conditions (40-90%)
without any encapsulation for 4 weeks.
PMID- 27500376
TI - TMPRSS2-ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate
cancer.
AB - T1a prostate cancers (cancer found incidentally in transurethral resection, <5%
of the tissue) are indolent tumors of the transition zone. The overexpression of
ERG and the inactivation of PTEN have been shown to be important drivers of
carcinogenesis in large series of prostate cancer, but the genetics of transition
zone tumors have not been well characterized. We evaluated the status of ERG and
PTEN in formalin-fixed paraffin-embedded tissue using immunohistochemical and
FISH analysis in 54 T1a transition zone tumors. The protein expression of ERG was
determined using a rabbit monoclonal antibody and nuclear staining was scored as
positive or negative. The genomic status of ERG was determined using three
colored FISH using an ERG-TMPRSS2 tri-color probe set. The protein expression of
PTEN was determined using a rabbit monoclonal antibody and cytoplasmic, and
nuclear staining was scored as positive or negative. The genomic status of PTEN
was determined using dual color FISH with a PTEN probe and a CEP10 probe. We
found ERG rearrangement in 2 of 54 tumors (4%), one with protein overexpression
by immunohistochemistry. PTEN inactivation was seen in 13 of 54 tumors (24%).
Nine of the 13 PTEN alleles were inactivated by hemizygous deletion. No
homozygous PTEN deletion was observed. PTEN deletion and ERG rearrangement were
mutually exclusive. ERG rearrangement was rare compared to peripheral zone tumors
and to PTEN inactivation in T1a transition zone tumors. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27500377
TI - Critical telomerase activity for uncontrolled cell growth.
AB - The lengths of the telomere regions of chromosomes in a population of cells are
modelled using a chemical master equation formalism, from which the evolution of
the average number of cells of each telomere length is extracted. In particular,
the role of the telomere-elongating enzyme telomerase on these dynamics is
investigated. We show that for biologically relevant rates of cell birth and
death, one finds a critical rate, R crit, of telomerase activity such that the
total number of cells diverges. Further, R crit is similar in magnitude to the
rates of mitosis and cell death. The possible relationship of this result to
replicative immortality and its associated hallmark of cancer is discussed.
PMID- 27500378
TI - Ionic-liquid-based dispersive liquid-liquid microextraction combined with
magnetic solid-phase extraction for the determination of aflatoxins B1 , B2 , G1
, and G2 in animal feeds by high-performance liquid chromatography with
fluorescence detection.
AB - A novel two-step extraction technique combining ionic-liquid-based dispersive
liquid-liquid microextraction with magnetic solid-phase extraction was developed
for the preconcentration and separation of aflatoxins in animal feedstuffs before
high-performance liquid chromatography coupled with fluorescence detection. In
this work, ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate was used
as the extractant in dispersive liquid-liquid microextraction, and hydrophobic
pelargonic acid modified Fe3 O4 magnetic nanoparticles as an efficient adsorbent
were applied to retrieve the aflatoxins-containing ionic liquid. Notably, the
target of magnetic nanoparticles was the ionic liquid rather than the aflatoxins.
Because of the rapid mass transfer associated with the dispersive liquid-liquid
microextraction and magnetic solid phase steps, fast extraction could be
achieved. The main parameters affecting the extraction recoveries of aflatoxins
were investigated and optimized. Under the optimum conditions, vortexing at 2500
rpm for 1 min in the dispersive liquid-liquid microextraction and magnetic solid
phase extraction and then desorption by sonication for 2 min with acetonitrile as
eluent. The recoveries were 90.3-103.7% with relative standard deviations of 3.2
6.4%. Good linearity was observed with correlation coefficients ranged from
0.9986 to 0.9995. The detection limits were 0.632, 0.087, 0.422 and 0.146 ng/mL
for aflatoxins B1 , B2, G1, and G2, respectively. The results were also compared
with the pretreatment method carried out by conventional immunoaffinity columns.
PMID- 27500379
TI - An innovative protocol for schwann cells extracellular matrix proteins
extraction.
AB - The evidence that extracellular matrix (ECM) components could represent new
targets for drugs designed to approach degenerative disease, requires their
analysis. Before the analysis, proteins should be extracted from ECM and
solubilized. Currently, few protocols for ECM proteins extraction and
solubilization are available in literature, and most of them are based mainly on
the use of proteolytic enzymes, such as trypsin, which often lead to proteins
damage. Moreover, no methods have been so far proposed to solubilize Schwann Cell
ECM, which may represent an important target for the therapy of neurodegenerative
disorders. In our study, we propose to solubilize SC ECM through the use of
surfactants and urea. We compared our method of solubilization, with one of that
proposed in literature for a general ECM, mainly based on the use of enzymes. We
want to highlight the benefit of solubilizing SC ECM, avoiding the use of
proteolytic enzymes. To compare the amount of proteins extracted with both
methods, MicroBCA assay was used, while the quality of the proteins extracted was
observed through the SDS-PAGE. The results obtained confirm a better
solubilization of SC ECM proteins with the proposed protocol, both quantitatively
and qualitatively, showing a higher concentration of proteins extracted and a
better enrichment of protein fractions, if compared to the enzyme-based protocol.
Our results show that SC ECM could be efficiently solubilized through the use of
surfactant and urea, avoiding the use of enzyme-base methods. (c) 2016 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3175-3180, 2016.
PMID- 27500380
TI - Recent Advances in Doping of Molybdenum Disulfide: Industrial Applications and
Future Prospects.
AB - Owing to their excellent physical properties, atomically thin layers of
molybdenum disulfide (MoS2 ) have recently attracted much attention due to their
nonzero-gap property, exceptionally high electrical conductivity, good thermal
stability, and excellent mechanical strength, etc. MoS2 -based devices exhibit
great potential for applications in optoelectronics and energy harvesting. Here,
a comprehensive review of various doping strategies is presented, including wet
doping and dry doping of atomically crystalline MoS2 thin layers, and the
progress made so far for their doping-based prospective applications is also
discussed. Finally, several significant research issues for the prospects of
doped-MoS2 in industry, as a guide for 2D material community, are also provided.
PMID- 27500381
TI - Long-term outcome characteristics in mesial temporal lobe epilepsy with and
without associated cortical dysplasia.
AB - OBJECT: The intention of our study was to identify predictive characteristics for
long-term seizure control and running down phenomenon after surgical treatment of
pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated
cortical dysplasia. MATERIALS AND METHODS: Our study comprises a consecutive
series of 458 patients who underwent surgical treatment for intractable mTLE at
the Epilepsy Center Freiburg. Data evaluated included semiology, duration and
frequency of seizures, results of presurgical diagnostics including video-EEG
monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results
were evaluated forming two groups: Group A consisted of isolated mesiotemporal
lesions. Group B comprised patients with mTLE and additional focal cortical
dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival
analysis, using log-rank-tests and a multivariate regression model. Postoperative
running down phenomenon was defined as seizure freedom after a period of gradual
reduction of postoperative seizure frequency. This was compared to patients with
ongoing epilepsy. RESULTS: Complete seizure freedom was achieved in 65.0% of
investigated patients at 1year and in 56.5% at long-term follow-up of >=5 years
after surgery. Corresponding results were 64.2% and 56.8% at 1 and >=5 years,
respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive
for favorable postoperative outcome in the total group were younger age at
surgery, shorter duration of epilepsy, absence of secondarily generalized tonic
clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal
epileptiform discharges (IEDs), complete resection of the lesion as well as
absence of postoperative epileptiform activity and of early postoperative
seizures. In subgroup analyses, patients of group A demonstrated longer
postoperative seizure-free intervals with adolescent age at surgery, short
duration of epilepsy before surgery and absence of SGTCS, whereas in patients of
group B ipsilateral temporal seizure onset and strictly unilateral IEDs in EEG as
well as complete resection were predictors for favorable seizure outcome.
Furthermore, absence of early postoperative seizures and of spikes in EEG were
predictive factors for long-term seizure-freedom in both subgroups. The running
down phenomenon was found in 33 (7.2%) patients. None of the parameters evaluated
demonstrated significant predictive power. Only late seizure onset and neoplastic
lesions showed a trend for postoperative gradual seizure reduction in
multivariate analyses. CONCLUSION: Depending on the presence or absence of focal
cortical dysplasia in addition to mesiotemporal structural alterations,
predictors of long-term seizure control differed regarding the relevant clinical
and electrophysiological features. This is important for specific patient
counseling in respective groups.
PMID- 27500382
TI - Regression of fibrosis and portal hypertension in HCV-associated cirrhosis and
sustained virologic response after interferon-free antiviral therapy.
AB - It is still controversial, whether and to what amount cirrhosis and portal
hypertension are reversible in patients with hepatitis C virus (HCV)-associated
cirrhosis and sustained virologic response (SVR) after interferon-free antiviral
therapy. In this study, we prospectively evaluated dynamics of liver and spleen
stiffness in HCV-infected patients with advanced liver disease and SVR after
interferon-free treatment. A total of 54 patients with HCV-associated cirrhosis
and SVR were included. Liver and spleen stiffness was measured at therapy
baseline (BL), end of treatment (EOT) and 24 weeks after EOT (FU24) by transient
liver elastography (L-TE) as well as by acoustic radiation force impulse of the
liver (L-ARFI) and spleen (S-ARFI), as well as biochemical, virologic and
clinical data. Improvement of liver and spleen stiffness was found in 44 of 50
(88%), 31 of 54 (57%) and 25 of 54 (46%) of patients assessed by L-TE, L-ARFI and
S-ARFI between baseline and FU24. Liver stiffness assessed by L-TE improved
between BL [median (range), 32.5 (9.1-75) kPa] and EOT [median (range), 21.3 (6.7
73.5) kPa; (P<.0001)], and between BL and FU24 [median (range), 21.2 (5.4-70)
kPa; (P<.0001)]. Liver stiffness assessed by L-ARFI improved between BL [median
(range), 2.7 (1.2-4.1) m/s] and FU24 [median (range), 2.4 (1.2-3.9) m/s; P=.002),
while spleen stiffness remained unchanged. Our data suggest that improvement of
liver stiffness may be rather due to reduced necroinflammation and may be due to
a less extent to regression of cirrhosis, as dynamics of liver stiffness
improvement was more pronounced between BL and EOT than BL and FU24.
PMID- 27500383
TI - The effects of Risk Factor-Targeted Lifestyle Counselling Intervention on working
age stroke patients' adherence to lifestyle change.
AB - INTRODUCTION: Since a history of stroke or transient ischaemic attack is a major
risk factor for a recurrent event, lifestyle counselling during the hospital
phase is an essential component of treatment and may increase the probability of
lifestyle change. AIMS AND OBJECTIVES: To study the effect of risk factor
targeted lifestyle counselling intervention on working-age stroke patients'
adherence to lifestyle changes. DESIGN: A quasi-experimental, nonequivalent
control group pretest-post-test design. METHODS: Stroke patients in an acute
neurological unit were divided into a control group (n = 75) receiving standard
counselling and an experimental group (n = 75) receiving risk factor-targeted
counselling. Lifestyle data and clinical outcomes were collected at hospital
between January 2010 and October 2011, while data on adherence to lifestyle
changes 3, 6, and 12 months after discharge. RESULTS: The baseline lifestyle
habits did not differ significantly other than in alcohol behaviour. Both groups
increased their intake, but the intervention group to a lesser degree. However,
the experimental group significantly lost their weight for the first 3 and 6
months; at 3 months reduction in cigarette consumption and at 6 months
significant increases in smoking cessation were also achieved. All improved some
of their lifestyle habits. Intervention was associated with support from nurses
as well as from family and friends. Adherence scores were higher in the
experimental group. CONCLUSION: Some short-term advantages in lifestyle habits
due to the intervention were noted. Participants in both groups improved some of
their lifestyle habits.
PMID- 27500384
TI - Candidate egg case silk genes for the spider Argiope argentata from differential
gene expression analyses.
AB - Orb-web weaving spiders produce a variety of task-specific silks from specialized
silk glands. The genetics underlying the synthesis of specific silk types are
largely unknown, and transcriptome analysis could be a powerful approach for
identifying candidate genes. However, de novo assembly and expression profiling
of silk glands with RNA-sequencing (RNAseq) are problematic because the few known
gene transcripts for silk proteins are extremely long and highly repetitive. To
identify candidate genes for tubuliform (egg case) silk synthesis by the orb
weaver Argiope argentata (Araneidae), we estimated transcript abundance using two
sequencing methods: RNAseq reads from throughout the length of mRNA molecules,
and 3' digital gene expression reads from the 3' region of mRNA molecules. Both
analyses identified similar sets of genes as differentially expressed when
comparing tubuliform and nonsilk gland tissue. However, incompletely assembled
silk gene transcripts were identified as differentially expressed because of
RNAseq read alignments to highly repetitive regions, confounding interpretation
of RNAseq results. Homologues of egg case silk protein (ECP) genes were
upregulated in tubuliform glands. This discovery is the first description of ECP
homologues in an araneid. We also propose additional candidate genes involved in
synthesis of tubuliform or other silk types.
PMID- 27500385
TI - Characterization of tunnel mutants reveals a catalytic step in ammonia delivery
by an aminoacyl-tRNA amidotransferase.
AB - The Helicobacter pylori Asp-tRNA(A) (sn) /Glu-tRNA(G) (ln) amidotransferase
(GatCAB) utilizes an uncommonly hydrophilic, ~ 40 A ammonia tunnel for
ammonia/ammonium transport between isolated active sites. Hydrophilicity of this
tunnel requires a distinct ammonia transport mechanism, which hypothetically
occurs through a series of deprotonation and protonation steps. To explore the
initiation of this relay mechanism, the highly conserved tunnel residue D185 (in
the GatA subunit) was enzymatically and computationally investigated by comparing
D185A, D185N, and D185E mutant enzymes to wild-type GatCAB. Our results indicate
that D185 acts as an acid/base residue, participating directly in catalysis. To
our knowledge, this is the first example of acid/base chemistry in a glutamine
dependent amidotransferase ammonia tunnel.
PMID- 27500386
TI - Adult mental health outcomes of child sexual abuse survivors born at extremely
low birth weight.
AB - The high prevalence of child sexual abuse (CSA) is concerning, particularly as
survivors are at increased risk for multiple adverse outcomes, including poor
mental health across the lifespan. Children born at an extremely low birth weight
(ELBW; <1000g) and who experience CSA may be a group that is especially
vulnerable to psychopathology later in life. However, no research has considered
the mental health risks associated with being born at ELBW and experiencing CSA.
In this study, we investigated the mental health of 179 ELBW survivors and 145
matched normal birth weight (NBW; >2500g) participants at ages 22-26 and 29-36.
At age 22-26, CSA was associated with increased odds of clinically significant
internalizing (OR=7.32, 95% CI: 2.31-23.23) and externalizing (OR=4.65, 95% CI:
1.11-19.51) problems among ELBW participants exposed to CSA compared to those who
did not, though confidence intervals were wide. At age 29-36, CSA was linked to
increased odds of any current (OR=3.43, 95% CI: 1.08-10.87) and lifetime
(OR=7.09, 95% CI: 2.00-25.03) non-substance use psychiatric disorders, however,
this did not hold after adjustment for covariates. Statistically significant
differences in mental health outcomes were not observed in NBW participants
exposed to CSA compared to NBW participants who were not exposed. Survivors of
significant perinatal adversity who are also exposed to CSA may be at higher risk
for psychopathology through the fourth decade of life.
PMID- 27500387
TI - Parental absence, child victimization, and psychological well-being in rural
China.
AB - Using cross-sectional data regarding 793 rural children aged 10-16 in Sichuan
Province of China, the present study examined the preceding-year rates of seven
forms of child victimization (physical assault, property crime, peer/sibling
victimization, child maltreatment, sexual victimization, witnessing family
violence, and exposure to community violence) and poly-victimization, and found
children's victimization experiences increased as the degree of parental absence
increased (from the presence of two biological parents, to parental migration and
parental separation and divorce). Elevated levels of depression were also found
among left-behind children and children of separated or divorced parents,
compared to children living with both biological parents; and child poly
victimization added to the risk of child depression. Certain demographic
characteristics (being a boy and younger) and parental factors were associated
with child victimization in rural China. This study highlights the need for child
protection in rural China, and in particular for parent-absent children.
PMID- 27500388
TI - Modification of tumor cell exosome content by transfection with wt-p53 and
microRNA-125b expressing plasmid DNA and its effect on macrophage polarization.
AB - Exosomes are responsible for intercellular communication between tumor cells and
others in the tumor microenvironment. These microvesicles promote oncogensis and
can support towards metastasis by promoting a pro-tumorogenic environment.
Modifying the exosomal content and exosome delivery are emerging novel cancer
therapies. However, the clinical translation is limited due to feasibility of
isolating and delivery of treated exosomes as well as an associated immune
response in patients. In this study, we provide proof-of-concept for a novel
treatment approach for manipulating exosomal content by genetic transfection of
tumor cells using dual-targeted hyaluronic acid-based nanoparticles. Following
transfection with plasmid DNA encoding for wild-type p53 (wt-p53) and microRNA
125b (miR-125b), we evaluate the transgene expression in the SK-LU-1 cells and in
the secreted exosomes. Furthermore, along with modulation of wt-p53 and miR-125b
expression, we also show that the exosomes (i.e., wt-p53/exo, miR-125b/exo and
combination/exo) have a reprogramed global miRNA profile. The miRNAs in the
exosomes were mainly related to the activation of genes associated with apoptosis
as well as p53 signaling. More importantly, these altered miRNA levels in the
exosomes could mediate macrophage repolarization towards a more pro
inflammatory/antitumor M1 phenotype. However, further studies, especially in vivo
studies, are warranted to assess the direct influence of such macrophage
reprogramming on cancer cells and oncogenesis post-treatment. The current study
provides a novel platform enabling the development of therapeutic strategies
affecting not only the cancer cells but also the tumor microenvironment by
utilizing the 'bystander effect' through genetic transfer with secreted exosomes.
Such modification could also support antitumor environment leading to decreased
oncogenesis.
PMID- 27500389
TI - Value of 3-Tesla multiparametric magnetic resonance imaging and targeted biopsy
for improved risk stratification in patients considered for active surveillance.
AB - OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging
(mpMRI) of the prostate and transrectal ultrasonography guided biopsy (TRUS-Bx)
with visual estimation in early risk stratification of patients with prostate
cancer on active surveillance (AS). PATIENTS AND METHODS: Patients with low-risk,
low-grade, localised prostate cancer were prospectively enrolled and submitted to
a 3-T 16-channel cardiac surface coil mpMRI of the prostate and confirmatory
biopsy (CBx), which included a standard biopsy (SBx) and visual estimation-guided
TRUS-Bx. Cancer-suspicious regions were defined using Prostate Imaging Reporting
and Data System (PI-RADS) scores. Reclassification occurred if CBx confirmed the
presence of a Gleason score >=7, greater than three positive fragments, or >=50%
involvement of any core. The performance of mpMRI for the prediction of CBx
results was assessed. Univariate and multivariate logistic regressions were
performed to study relationships between age, prostate-specific antigen (PSA)
level, PSA density (PSAD), number of positive cores in the initial biopsy, and
mpMRI grade on CBx reclassification. Our report is consistent with the Standards
of Reporting for MRI-targeted Biopsy Studies (START) guidelines. RESULTS: In all,
105 patients were available for analysis in the study. From this cohort, 42 (40%)
had PI-RADS 1, 2, or 3 lesions and 63 (60%) had only grade 4 or 5 lesions.
Overall, 87 patients underwent visual estimation TRUS-Bx. Reclassification among
patients with PI-RADS 1, 2, 3, 4, and 5 was 0%, 23.1%, 9.1%, 74.5%, and 100%,
respectively. Overall, mpMRI sensitivity, specificity, positive predictive value,
and negative predictive value for disease reclassification were 92.5%, 76%, 81%,
and 90.5%, respectively. In the multivariate analysis, only PSAD and mpMRI
remained significant for reclassification (P < 0.05). In the cross-tabulation,
SBx would have missed 15 significant cases detected by targeted biopsy, but SBx
did detect five cases of significant cancer not detected by targeted biopsy
alone. CONCLUSION: Multiparametric magnetic resonance imaging is a significant
tool for predicting cancer severity reclassification on CBx among AS candidates.
The reclassification rate on CBx is particularly high in the group of patients
who have PI-RADS grades 4 or 5 lesions. Despite the usefulness of visual-guided
biopsy, it still remains highly recommended to retrieve standard fragments during
CBx in order to avoid missing significant tumours.
PMID- 27500390
TI - Optimal sequencing of postoperative radiotherapy and chemotherapy in IIIA-N2 non
small cell lung cancer.
PMID- 27500392
TI - Granulomatosis with polyangiitis-associated acute subglottic stenosis in a 13
year-old boy: a case report.
AB - We present a case of a child with granulomatosis with polyangiitis, admitted with
acute respiratory distress attributed to subglottic stenosis. The anesthetic
management and potential complications are described.
PMID- 27500391
TI - MR neurography for the evaluation of CIDP.
AB - INTRODUCTION: To visualize peripheral nerves in patients with chronic
inflammatory demyelinating polyneuropathy (CIDP), we used MR imaging. We also
quantified the volumes of the brachial and lumbar plexus and their nerve roots.
METHODS: Thirteen patients with CIDP and 12 healthy volunteers were enrolled.
Whole-body MR neurography based on diffusion-weighted whole-body imaging with
background body signal suppression (DWIBS) was performed. Peripheral nerve
volumes were calculated from serial axial MR images. RESULTS: The peripheral
nervous system was visualized with 3-dimensional reconstruction. Volumes ranged
from 8.7 to 49.5 cm3 /m2 in the brachial plexus and nerve roots and from 10.2 to
53.5 cm3 /m2 in the lumbar plexus and nerve roots. Patients with CIDP had
significantly larger volumes than controls (P < 0.05), and volume was positively
correlated with disease duration. CONCLUSIONS: MR neurography and the measurement
of peripheral nerve volume are useful for diagnosing and assessing CIDP. Muscle
Nerve 55: 483-489, 2017.
PMID- 27500393
TI - Graphene-based tunable terahertz plasmon-induced transparency metamaterial.
AB - A novel terahertz plasmon induced transparency (PIT) metamaterial structure
consisting of single-layered graphene microstructures was proposed and
numerically studied in this study. A pronounced transparency peak was obtained in
the transmission spectrum, which resulted from the destructive interference
between the graphene dipole and monopole antennas. Further investigations have
shown that the spectral location and lineshape of the transparency peak can be
dynamically controlled by tuning the Fermi level in graphene. Since the monopole
antennas in our designed structure exist in a continuous form, a more convenient
method for tunablity is available by applying a gate voltage compared to those
structures with discrete graphene patterns. This work may open up new avenues for
designing tunable terahertz functional devices and slow light devices.
PMID- 27500394
TI - Experience and outcomes for relatives of patients dying in the ICU: the CAESAR
tool.
PMID- 27500395
TI - Stigmatizing attitudes in nurses towards people with mental illness: a cross
sectional study in primary settings in Finland.
AB - WHAT IS KNOWN ON THE SUBJECT?: Stigma related to mental illnesses is a great
burden on societies globally. Factors associated with nurses' attitudes towards
people with mental illness in health-care settings are discrepant. Stigmatized
attitudes among staff members towards patients with mental illness have widely
been studied in various specialized health care contexts, but less often in
primary health-care settings. WHAT THIS PAPER ADDS TO THE EXISTING KNOWLEDGE?:
Nurses' attitudes towards people with mental illness in general were positive in
primary care health settings. Younger nurses expressed feeling afraid of mentally
ill patients. They not only lacked a feeling of safety around these patients but
were also often of the opinion that people with mental illness should be
segregated from the general population. WHAT ARE THE IMPLICATIONS FOR PRACTICE?:
Systematic and continuous mental health on-the-job training for primary care
nurses is recommended to strengthen the positive attitudes of young nurses
towards patients. Young nurses especially should be prevented from developing
stigmatized attitudes towards patients with mental problems and to ensure a
skilled workforce for the future in this demanding area of health care. ABSTRACT:
Introduction Despite the development of mental health services in many countries,
nurses working in different health care specialties may still have concerns and
negative attitudes towards people with mental illness. Aim To describe nurses'
attitudes towards people with mental illness and examine factors associated with
their attitudes in primary care health centres. Method The data were collected
from nursing staff (N = 264, response rate 84%) in 15 primary care health centres
in two Finnish cities (spring 2014) with a self-report questionnaire (Attribution
Questionnaire-27, Corrigan 2003) and analysed by descriptive statistics and
multiway covariance analysis. Results Nurses' attitudes towards people with
mental illness were generally positive. The nurses mostly reported willingness to
help and feelings of concern and sympathy towards these patients. However,
younger nurses or those without additional mental health training expressed a
fear of patients. Discussion Special attention should be paid to nursing
education and on-the-job training to prevent young nurses from developing
stigmatized attitudes towards patients. Implications for practice Higher
confidence in nursing staff could ensure a skilled work force in areas of mental
health in the future, prevent young nurses from developing a fear of patients at
work and support positive attitudes towards patients with mental problems.
PMID- 27500396
TI - Strong phylogeographic co-structure between the anther-smut fungus and its white
campion host.
AB - Although congruence between host and pathogen phylogenies has been extensively
investigated, the congruence between host and pathogen genetic structures at the
within-species level has received little attention. Using an unprecedented and
comprehensive collection of associated plant-pathogen samples, we investigated
the degree of congruence between the genetic structures across Europe of two
evolutionary and ecological model organisms, the anther-smut pathogen
Microbotryum lychnidis-dioicae and its host plant Silene latifolia. We
demonstrated a significant and particularly strong level of host-pathogen co
structure, with three main genetic clusters displaying highly similar spatial
ranges in Western Europe, Eastern Europe and Italy, respectively. Correcting for
the geographical component of genetic variation, significant correlations were
still found between the genetic distances of anther-smut and host populations.
Inoculation experiments suggested plant local adaptation, at the cluster level,
for resistance to pathogens. These findings indicate that the pathogen remained
isolated in the same fragmented southern refugia as its host plant during the
last glaciation, and that little long-distance dispersal has occurred since the
recolonization of Europe for either the plant or the pathogen, despite their
known ability to travel across continents. This, together with the inoculation
results, suggests that coevolutionary and competitive processes may be drivers of
host-pathogen co-structure.
PMID- 27500397
TI - To improve outcomes of gallbladder cancer we need to better understand it!
PMID- 27500398
TI - Post-prophylaxis Toxoplasma chorioretinitis following donor-recipient mismatched
liver transplantation.
AB - Toxoplasmosis may be transferred by organ transplantation. The most common
clinical presentation is with multisystem disease, although isolated ocular
toxoplasmosis has been described. Many centers have suggested that universal use
of co-trimoxazole prophylaxis obviates the need for specific Toxoplasma testing.
We report a case of donor-acquired ocular toxoplasmosis after liver
transplantation despite co-trimoxazole prophylaxis. The diagnosis was confirmed
by Toxoplasma polymerase chain reaction assay in conjunction with seroconversion.
The fact that the infection was donor acquired was confirmed by serological
mismatch and the absence of sporozoite-specific antigen antibody in the
recipient.
PMID- 27500399
TI - Direct Acoustic Stimulation at the Lateral Canal: An Alternative Route to the
Inner Ear?
AB - Severe to profound mixed hearing loss is associated with hearing rehabilitation
difficulties. Recently, promising results for speech understanding were obtained
with a direct acoustic cochlear implant (DACI). The surgical implantation of a
DACI with standard coupling through a stapedotomy can however be regarded as
challenging. Therefore, in this experimental study, the feasibility of direct
acoustic stimulation was investigated at an anatomically and surgically more
accessible inner ear site. DACI stimulation of the intact, blue-lined and opened
lateral semicircular canal (LC) was investigated and compared with standard oval
window (OW) coupling. Additionally, stapes footplate fixation was induced. Round
window (RW) velocity, as a measure of the performance of the device and its
coupling efficiency, was determined in fresh-frozen human cadaver heads. Using
single point laser Doppler vibrometry, RW velocity could reliably be measured in
low and middle frequency range, and equivalent sound pressure level (LE) output
was calculated. Results for the different conditions obtained in five heads were
analyzed in subsequent frequency ranges. Comparing the difference in RW membrane
velocity showed higher LE in the LC opened condition [mean: 103 equivalent dB
SPL], than in LC intact or blue-lined conditions [63 and 74 equivalent dB SPL,
respectively]. No difference was observed between the LC opened and the standard
OW condition. Inducing stapes fixation, however, led to a difference in the low
frequency range of LE compared to LC opened. In conclusion, this feasibility
study showed promising results for direct acoustic stimulation at this specific
anatomically and surgically more accessible inner ear site. Future studies are
needed to address the impact of LC stimulation on cochlear micromechanics and on
the vestibular system like dizziness and risks of hearing loss.
PMID- 27500401
TI - Cellobiose dehydrogenase and chitosan-based lysozyme responsive materials for
antimicrobial wound treatment.
AB - The treatment of wound infection still constitutes a major threat in health care
due to the increasing number of bacterial resistances and the difficulty of
timely infection detection. Here, we present a smart antimicrobial system that is
activated in case of infection based on elevated lysozyme activities. N-acetyl
chitosan (degree of N-acetylation: 40%) was synthesized and hydrolysis by
lysozyme in artificial wound fluid (AWF) was demonstrated. This resulted in the
formation of N-acetylated chito oligosaccharides (COS) with a degree of
polymerization of 2-5 units. The COS were shown to serve as substrate for
cellobiose dehydrogenase (CDH) leading to the production of 1 mM antimicrobial
hydrogen peroxide (H2 O2 ) after 24 h incubation at 37 degrees C in AWF. Growth
inhibition was seen upon incubation of Escherichia coli and Staphylococcus aureus
with this chitosan-CDH system over 8 h. This approach represents the first self
regulating system for the infection responsive inhibition of bacterial growth in
response to lysozyme as infection biomarker. Biotechnol. Bioeng. 2017;114: 416
422. (c) 2016 Wiley Periodicals, Inc.
PMID- 27500400
TI - A MultiSite Gateway Toolkit for Rapid Cloning of Vertebrate Expression Constructs
with Diverse Research Applications.
AB - Recombination-based cloning is a quick and efficient way to generate expression
vectors. Recent advancements have provided powerful recombinant DNA methods for
molecular manipulations. Here, we describe a novel collection of three-fragment
MultiSite Gateway cloning system-compatible vectors providing expanded molecular
tools for vertebrate research. The components of this toolkit encompass a broad
range of uses such as fluorescent imaging, dual gene expression, RNA
interference, tandem affinity purification, chemically-inducible dimerization and
lentiviral production. We demonstrate examples highlighting the utility of this
toolkit for producing multi-component vertebrate expression vectors with diverse
primary research applications. The vectors presented here are compatible with
other Gateway toolkits and collections, facilitating the rapid generation of a
broad range of innovative DNA constructs for biological research.
PMID- 27500402
TI - Correction: Bayesian Multi-Trait Analysis Reveals a Useful Tool to Increase Oil
Concentration and to Decrease Toxicity in Jatropha curcas L.
AB - [This corrects the article DOI: 10.1371/journal.pone.0157038.].
PMID- 27500403
TI - A Complex System of Glacial Sub-Refugia Drives Endemic Freshwater Biodiversity on
the Tibetan Plateau.
AB - Although only relatively few freshwater invertebrate families are reported from
the Tibetan Plateau, the degree of endemism may be high. Many endemic lineages
occur within permafrost areas, raising questions about the existence of isolated
intra-plateau glacial refugia. Moreover, if such refugia existed, it might be
instructive to learn whether they were associated with lakes or with more dynamic
ecosystems such as ponds, wetlands, or springs. To study these hypotheses, we
used pulmonate snails of the plateau-wide distributed genus Radix as model group
and the Lake Donggi Cona drainage system, located in the north-eastern part of
the plateau, as model site. First, we performed plateau-wide phylogenetic
analyses using mtDNA data to assess the overall relationships of Radix
populations inhabiting the Lake Donggi Cona system for revealing refugial
lineages. We then conducted regional phylogeographical analyses applying a
combination of mtDNA and nuclear AFLP markers to infer the local structure and
demographic history of the most abundant endemic Radix clade for identifying
location and type of (sub-)refugia within the drainage system. Our phylogenetic
analysis showed a high diversity of Radix lineages in the Lake Donggi Cona
system. Subsequent phylogeographical analyses of the most abundant endemic clade
indicated a habitat-related clustering of genotypes and several Late Pleistocene
spatial/demographic expansion events. The most parsimonious explanation for these
patterns would be a scenario of an intra-plateau glacial refugium in the Lake
Donggi Cona drainage system, which might have consisted of isolated sub-refugia.
Though the underlying processes remain unknown, an initial separation of lake and
watershed populations could have been triggered by lake-level fluctuations before
and during the Last Glacial Maximum. This study inferred the first intra-plateau
refugium for freshwater animals on the Tibetan Plateau. It thus sheds new light
on the evolutionary history of its endemic taxa and provides important insights
into the complex refugial history of a high-altitude ecosystem.
PMID- 27500404
TI - Comparison of Two New Robust Parameter Estimation Methods for the Power Function
Distribution.
AB - Estimation of any probability distribution parameters is vital because imprecise
and biased estimates can be misleading. In this study, we investigate a flexible
power function distribution and introduced new two methods such as, probability
weighted moments, and generalized probability weighted methods for its
parameters. We compare their results with L-moments, trimmed L-moments by a
simulation study and a real data example based on performance measures such as,
mean square error and total deviation. We concluded that all the methods perform
well in the case of large sample size (n>30), however, the generalized
probability weighted moment method performs better for small sample size.
PMID- 27500405
TI - Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype
Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.
AB - The aim of this study was to evaluate specific glutathione S-transferase (GST)
gene variants as determinants of risk in patients with clear cell renal cell
carcinoma (cRCC), independently or simultaneously with established RCC risk
factors, as well as to discern whether phenotype changes reflect genotype
associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199
cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA
adducts were determined in DNA samples obtained from cRCC patients by ELISA
method. Significant association between GST genotype and risk of cRCC development
was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p<0.001,
respectively). Furthermore, 22% of all recruited cRCC patients were carriers of
combined GSTM1-null, GSTT1-active, GSTA1-low activity and GSTP1-variant genotype,
exhibiting 9.32-fold elevated cRCC risk compared to the reference genotype
combination (p = 0.04). Significant association between GST genotype and cRCC
risk in smokers was found only for the GSTP1 genotype, while GSTM1-null/GSTP1
variant/GSTA1 low-activity genotype combination was present in 94% of smokers
with cRCC, increasing the risk of cRCC up to 7.57 (p = 0.02). Furthermore, cRCC
smokers with GSTM1-null genotype had significantly higher concentration of BPDE
DNA adducts in comparison with GSTM1-active cRCC smokers (p = 0.05). GSTM1,
GSTT1, GSTA1 and GSTP1 polymorphisms might be associated with the risk of cRCC,
with special emphasis on GSTM1-null and GSTP1-variant genotypes. Combined GSTM1
null, GSTT1-active, GSTA1 low activity and GSTP1-variant genotypes might be
considered as "risk-carrying genotype combination" in cRCC.
PMID- 27500406
TI - Diminished KCC2 confounds synapse specificity of LTP during senescence.
AB - The synapse specificity of long-term potentiation (LTP) ensures that no
interference arises from inputs irrelevant to the memory to be encoded. In
hippocampi of aged (21-28 months) mice, LTP was relayed to unstimulated synapses,
blemishing its synapse specificity. Diminished levels of the K(+)/Cl(-)
cotransporter KCC2 and a depolarizing GABAA receptor-mediated synaptic component
following LTP were the most likely causes for the spreading of potentiation,
unveiling mechanisms hindering information storage in the aged brain and
identifying KCC2 as a potential target for intervention.
PMID- 27500408
TI - Large-Scale Production of Cardiomyocytes from Human Pluripotent Stem Cells Using
a Highly Reproducible Small Molecule-Based Differentiation Protocol.
AB - Maximizing the benefit of human pluripotent stem cells (hPSCs) for research,
disease modeling, pharmaceutical and clinical applications requires robust
methods for the large-scale production of functional cell types, including
cardiomyocytes. Here we demonstrate that the temporal manipulation of WNT, TGF
beta, and SHH signaling pathways leads to highly efficient cardiomyocyte
differentiation of single-cell passaged hPSC lines in both static suspension and
stirred suspension bioreactor systems. Employing this strategy resulted in ~ 100%
beating spheroids, consistently containing > 80% cardiac troponin T-positive
cells after 15 days of culture, validated in multiple hPSC lines. We also report
on a variation of this protocol for use with cell lines not currently adapted to
single-cell passaging, the success of which has been verified in 42 hPSC lines.
Cardiomyocytes generated using these protocols express lineage-specific markers
and show expected electrophysiological functionalities. Our protocol presents a
simple, efficient and robust platform for the large-scale production of human
cardiomyocytes.
PMID- 27500407
TI - Connectivity precedes function in the development of the visual word form area.
AB - What determines the cortical location at which a given functionally specific
region will arise in development? We tested the hypothesis that functionally
specific regions develop in their characteristic locations because of pre
existing differences in the extrinsic connectivity of that region to the rest of
the brain. We exploited the visual word form area (VWFA) as a test case, scanning
children with diffusion and functional imaging at age 5, before they learned to
read, and at age 8, after they learned to read. We found the VWFA developed
functionally in this interval and that its location in a particular child at age
8 could be predicted from that child's connectivity fingerprints (but not
functional responses) at age 5. These results suggest that early connectivity
instructs the functional development of the VWFA, possibly reflecting a general
mechanism of cortical development.
PMID- 27500409
TI - An Efficient Method to Obtain Dedifferentiated Fat Cells.
AB - Tissue engineering and cell therapy hold great promise clinically. In this
regard, multipotent cells, such as mesenchymal stem cells (MSCs), may be used
therapeutically, in the near future, to restore function to damaged organs.
Nevertheless, several technical issues, including the highly invasive procedure
of isolating MSCs and the inefficiency surrounding their amplification, currently
hamper the potential clinical use of these therapeutic modalities. Herein, we
introduce a highly efficient method for the generation of dedifferentiated fat
cells (DFAT), MSC-like cells. Interestingly, DFAT cells can be differentiated
into several cell types including adipogenic, osteogenic, and chondrogenic cells.
Although other groups have previously presented various methods for generating
DFAT cells from mature adipose tissue, our method allows us to produce DFAT cells
more efficiently. In this regard, we demonstrate that DFAT culture medium (DCM),
supplemented with 20% FBS, is more effective in generating DFAT cells than DMEM,
supplemented with 20% FBS. Additionally, the DFAT cells produced by our cell
culture method can be redifferentiated into several tissue types. As such, a very
interesting and useful model for the study of tissue dedifferentiation is
presented.
PMID- 27500411
TI - Comparison of Methods for Predicting the Compositional Dependence of the Density
and Refractive Index of Organic-Aqueous Aerosols.
AB - Representing the physicochemical properties of aerosol particles of complex
composition is of crucial importance for understanding and predicting aerosol
thermodynamic, kinetic, and optical properties and processes and for interpreting
and comparing analysis methods. Here, we consider the representations of the
density and refractive index of aqueous-organic aerosol with a particular focus
on the dependence of these properties on relative humidity and water content,
including an examination of the properties of solution aerosol droplets existing
at supersaturated solute concentrations. Using bulk phase measurements of density
and refractive index for typical organic aerosol components, we provide robust
approaches for the estimation of these properties for aerosol at any intermediate
composition between pure water and pure solute. Approximately 70 compounds are
considered, including mono-, di- and tricarboxylic acids, alcohols, diols,
nitriles, sulfoxides, amides, ethers, sugars, amino acids, aminium sulfates, and
polyols. We conclude that the molar refraction mixing rule should be used to
predict the refractive index of the solution using a density treatment that
assumes ideal mixing or, preferably, a polynomial dependence on the square root
of the mass fraction of solute, depending on the solubility limit of the organic
component. Although the uncertainties in the density and refractive index
predictions depend on the range of subsaturated compositional data available for
each compound, typical errors for estimating the solution density and refractive
index are less than +/-0.1% and +/-0.05%, respectively. Owing to the direct
connection between molar refraction and the molecular polarizability, along with
the availability of group contribution models for predicting molecular
polarizability for organic species, our rigorous testing of the molar refraction
mixing rule provides a route to predicting refractive indices for aqueous
solutions containing organic molecules of arbitrary structure.
PMID- 27500410
TI - Real-time X-ray Imaging of Lung Fluid Volumes in Neonatal Mouse Lung.
AB - At birth, the lung undergoes a profound phenotypic switch from secretion to
absorption, which allows for adaptation to breathing independently. Promoting and
sustaining this phenotype is critically important in normal alveolar growth and
gas exchange throughout life. Several in vitro studies have characterized the
role of key regulatory proteins, signaling molecules, and steroid hormones that
can influence the rate of lung fluid clearance. However, in vivo examinations
must be performed to evaluate whether these regulatory factors play important
physiological roles in regulating perinatal lung liquid absorption. As such, the
utilization of real time X-ray imaging to determine perinatal lung fluid
clearance, or pulmonary edema, represents a technological advancement in the
field. Herein, we explain and illustrate an approach to assess the rate of
alveolar lung fluid clearance and alveolar flooding in C57BL/6 mice at post natal
day 10 using X-ray imaging and analysis. Successful implementation of this
protocol requires prior approval from institutional animal care and use
committees (IACUC), an in vivo small animal X-ray imaging system, and compatible
molecular imaging software.
PMID- 27500412
TI - Identification and Investigation of Novel Binding Fragments in the Fatty Acid
Binding Protein 6 (FABP6).
AB - Fatty acid binding protein 6 (FABP6) is a potential drug discovery target, which,
if inhibited, may have a therapeutic benefit for the treatment of diabetes.
Currently, there are no published inhibitors of FABP6, and with the target
believed to be amenable to fragment-based drug discovery, a structurally enabled
program was initiated. This program successfully identified fragment hits using
the surface plasmon resonance (SPR) platform. Several hits were validated with
SAR and were found to be displaced by the natural ligand taurocholate. We report
the first crystal structure of human FABP6 in the unbound form, in complex with
cholate, and with one of the key fragments.
PMID- 27500413
TI - Adverse Childhood Experiences and Cervical Cancer Screening.
AB - BACKGROUND: Adverse childhood experiences (ACEs) have been associated with an
increased risk of a variety of diseases, including cancer. However, research has
largely ignored how ACEs impact cancer screening, a potential intermediate
outcome. As such, the present study examined the association between ACEs and
ever and recent use of Papanicolaou (Pap) test, among women aged 21 and older.
MATERIALS AND METHODS: Analyses used the 2009 Tennessee Behavioral Risk Factor
Surveillance System (n = 1527) to model odds of ever and recently (within the
last 3 years) engaging in Pap tests screening from nine different adversities.
Bivariate and multivariate logistic regression models were run to accomplish
this. RESULTS: In bivariate and multivariate models, living in a household in
which adults treated each other violently increased odds of ever receiving a Pap
test. In bivariate models, physical and sexual abuse was associated with
decreased odds of receiving a recent Pap test. After accounting for confounders,
only the latter association remained significant. CONCLUSIONS: Results highlight
a potential mechanism by which early childhood experiences can impact the
development of cervical cancer. Providers of care should consider modifications
to their screening practices, including screening for child abuse, to better
serve all women.
PMID- 27500414
TI - Application of Free Energy Perturbation for the Design of BACE1 Inhibitors.
AB - Novel spiroaminodihydropyrroles probing for optimized interactions at the P3
pocket of beta-secretase 1 (BACE1) were designed with the use of free energy
perturbation (FEP) calculations. The resulting molecules showed pIC50 potencies
in enzymatic BACE1 inhibition assays ranging from approximately 5 to 7. Good
correlation was observed between the predicted activity from the FEP calculations
and experimental activity. Simulations run with a default 5 ns approach delivered
a mean unsigned error (MUE) between prediction and experiment of 0.58 and 0.91
kcal/mol for retrospective and prospective applications, respectively. With
longer simulations of 10 and 20 ns, the MUE was in both cases 0.57 kcal/mol for
the retrospective application, and 0.69 and 0.59 kcal/mol for the prospective
application. Other considerations that impact the quality of the calculations are
discussed. This work provides an example of the value of FEP as a computational
tool for drug discovery.
PMID- 27500415
TI - Hydrogenated Cagelike Titania Hollow Spherical Photocatalysts for Hydrogen
Evolution under Simulated Solar Light Irradiation.
AB - We synthesized the hydrogenated cagelike TiO2 hollow spheres through a facile
sacrificial template method. After the hydrogenation treatment, the disordered
surface layer and cagelike pores were generated on the shell of the hollow
spheres. The spheres exhibit a high hydrogen evolution rate of 212.7 +/- 10.6
MUmol h(-1) (20 mg) under the simulated solar light irradiation, which is ~12
times higher than the hydrogenated TiO2 solid spheres and is ~9 times higher than
the original TiO2 hollow spheres. The high activity results from the unique
architectures and hydrogenation. Both the multiple reflection that was improved
by the cagelike hollow structures and the red shift of the absorption edge that
was induced by hydrogenation can enhance the ultraviolet and visible light
absorption. In addition, the high concentration of oxygen vacancies, as well as
the hydrogenated disordered surface layer, can improve the efficiency for
migration and separation of generated charge carriers.
PMID- 27500416
TI - Residue-specific Incorporation of Noncanonical Amino Acids into Model Proteins
Using an Escherichia coli Cell-free Transcription-translation System.
AB - The canonical set of amino acids leads to an exceptionally wide range of protein
functionality. Nevertheless, the set of residues still imposes limitations on
potential protein applications. The incorporation of noncanonical amino acids can
enlarge this scope. There are two complementary approaches for the incorporation
of noncanonical amino acids. For site-specific incorporation, in addition to the
endogenous canonical translational machineries, an orthogonal aminoacyl-tRNA
synthetase-tRNA pair must be provided that does not interact with the canonical
ones. Consequently, a codon that is not assigned to a canonical amino acid,
usually a stop codon, is also required. This genetic code expansion enables the
incorporation of a noncanonical amino acid at a single, given site within the
protein. The here presented work describes residue-specific incorporation where
the genetic code is reassigned within the endogenous translational system. The
translation machinery accepts the noncanonical amino acid as a surrogate to
incorporate it at canonically prescribed locations, i.e., all occurrences of a
canonical amino acid in the protein are replaced by the noncanonical one. The
incorporation of noncanonical amino acids can change the protein structure,
causing considerably modified physical and chemical properties. Noncanonical
amino acid analogs often act as cell growth inhibitors for expression hosts since
they modify endogenous proteins, limiting in vivo protein production. In vivo
incorporation of toxic noncanonical amino acids into proteins remains
particularly challenging. Here, a cell-free approach for a complete replacement
of L-arginine by the noncanonical amino acid L-canavanine is presented. It
circumvents the inherent difficulties of in vivo expression. Additionally, a
protocol to prepare target proteins for mass spectral analysis is included. It is
shown that L-lysine can be replaced by L-hydroxy-lysine, albeit with lower
efficiency. In principle, any noncanonical amino acid analog can be incorporated
using the presented method as long as the endogenous in vitro translation system
recognizes it.
PMID- 27500417
TI - HPLC-based Assay to Monitor Extracellular Nucleotide/Nucleoside Metabolism in
Human Chronic Lymphocytic Leukemia Cells.
AB - This method describes a sensitive, specific, reliable and reproducible reverse
phase high-performance liquid chromatography (RP-HPLC) assay developed and
validated for the quantification of extracellular purine nucleotides and
nucleosides produced by purified chronic lymphocytic leukemia (CLL) cells under
different culture conditions. The chromatographic separation of adenosine 5'
monophosphate (AMP), adenosine (ADO) and inosine (INO) is performed at RT on a
silica-based, reversed-phase column that is used for polar compound retention.
The method includes a binary mobile phase, which consists of 7 mM ammonium
acetate and acetonitrile with a flow rate of 1.00 ml/min. The eluates are
monitored using a Photodiode Array UV detector set at 260 nm. A standard
calibration curve is generated to calculate the equation for the analytical
quantification of each purine compound. System control, data acquisition and
analysis are then performed. Applying this protocol, AMP, INO and ADO elute at 7,
11 and 11.9 min, respectively, and the total run time for each sample is 20 min.
This protocol may be applied to different cell types and cell lines (both
suspension and adherent), using culture media as matrix. The advantages are easy
and fast sample preparation and the requirement of a small amount of supernatant
for analysis. Furthermore, the use of a serum-free medium allows skipping the
protein precipitation step with acetonitrile that impacts the final concentration
of purine compounds. One of the limitations of the method is the requirement of
the equilibration column run before each single sample run, making the total run
time of the experiment longer and preventing high throughput screening
applications.
PMID- 27500418
TI - New isocoumarin and stilbenoid derivatives from the tubers of Sparganium
stoloniferum (Buch.-Ham.).
AB - A new isocoumarin derivative 8,5'-dihydroxy-6'-methoxy-4-phenyl-5,2'
oxidoisocoumarin (1) and a new stilbenoid derivative methyl 5-hydroxy-2-(2
hydroxyphenyl)benzofuran-4-carboxylate (2) together with nine known compounds (3
11) were isolated from the tubers of Sparganium stoloniferum Buch.-Ham.. Another
stilbenoid derivative (3) and a xanthone (4) were identified as new natural
products and compounds 5-10 were obtained for the first time from the genus
Sparganium. All their structures were elucidated by comprehensive spectroscopic
analysis and comparison with available literature information.
PMID- 27500419
TI - Comparison of Light Penetration of Continuous Wave 810 nm and Superpulsed 904 nm
Wavelength Light in Anesthetized Rats.
AB - OBJECTIVE: The purpose of this study was to investigate light transmission of
continuous wave (CW) 810 nm wavelength light and 904 nm wavelength superpulsed
light through skin and gastrocnemius muscle and skin only using an anesthetized
Sprague-Dawley rat model. MATERIALS AND METHODS: The hair was shaved from the
left thigh region of the anesthetized rats and a detector, which measured fluence
rate, was placed either in the fascial plane deep into the muscle or below the
dermis. The laser probe was placed in contact with the surface of the skin and
measurements were taken for 4, 5, 10, 15, and 20 min depending on the experiment.
RESULTS: The initial fluence rate measurements through the muscle and skin
demonstrated that if the 904 nm wavelength superpulsed laser was turned on for a
minimum of 15 min, there was no increase in light penetration over time. With
appropriate warm-up periods, both lasers had stable output powers, which were
reflected in stable fluence rate measurements over 4 min. The percentages of
light transmission (fluence rate) through muscle and skin were 7.42% (810 nm
wavelength) and 4.01% (904 nm wavelength) and through skin were 24.63% (810 nm
wavelength) and 19.94% (904 nm wavelength). These data prove that transmission of
CW 810 nm wavelength light through muscle and skin and skin alone is greater than
transmission of superpulsed 904 nm wavelength light. CONCLUSIONS: It has been
previously reported that superpulsing 904 nm wavelength light increased depth of
penetration over time due to photobleaching. Based on our data, the observed
increase in light penetration over time was due to an insufficient warm-up period
of the superpulsed laser.
PMID- 27500420
TI - March 2016 (vol. 214, no. 3, pages 403-6).
PMID- 27500421
TI - The Necessity of OCT-4 and CDX2 for Early Development and Gene Expression
Involved in Differentiation of Inner Cell Mass and Trophectoderm Lineages in
Bovine Embryos.
AB - The functions of POU class 5 transcription factor 1 (Oct-4) and caudal-type
homeobox 2 (Cdx2) in the differentiation of the murine inner cell mass (ICM) and
trophectoderm (TE) have been described in detail. However, little is known about
the roles of OCT-4 and CDX2 in preimplantation bovine embryos. To elucidate their
functions during early development in bovine embryos, we performed OCT-4 and CDX2
downregulation using RNA interference. We injected OCT-4- or CDX2-specific short
interfering RNAs (siRNAs) into bovine zygotes. The rate of blastocyst development
of OCT-4-downregulated embryos was lower compared with uninjected or control
siRNA-injected embryos. Gene expression analysis revealed decreased CDX2 and
fibroblast growth factor 4 expression in OCT-4-downregulated embryos. CDX2
downregulated embryos developed to the blastocyst stage; however, in most cases,
blastocoel formation was delayed. Gene expression analysis revealed decreased
GATA3 expression and elevated NANOG expression in CDX2-downregulated embryos. In
conclusion, OCT-4 and CDX2 are essential for early development and gene
expression involved in differentiation of ICM and TE lineages in bovine embryos.
PMID- 27500422
TI - Two Polymorphic Forms of a Six-Coordinate Mononuclear Cobalt(II) Complex with
Easy-Plane Anisotropy: Structural Features, Theoretical Calculations, and Field
Induced Slow Relaxation of the Magnetization.
AB - A mononuclear cobalt(II) complex [Co(3,5-dnb)2(py)2(H2O)2] {3,5-Hdnb = 3,5
dinitrobenzoic acid; py = pyridine} was isolated in two polymorphs, in space
groups C2/c (1) and P21/c (2). Single-crystal X-ray diffraction analyses reveal
that 1 and 2 are not isostructural in spite of having equal formulas and ligand
connectivity. In both structures, the Co(II) centers adopt octahedral {CoN2O4}
geometries filled by pairs of mutually trans terminal 3,5-dnb, py, and water
ligands. However, the structures of 1 and 2 disclose distinct packing patterns
driven by strong intermolecular O-H...O hydrogen bonds, leading to their 0D->2D
(1) or 0D->1D (2) extension. The resulting two-dimensional layers and one
dimensional chains were topologically classified as the sql and 2C1 underlying
nets, respectively. By means of DFT theoretical calculations, the energy
variations between the polymorphs were estimated, and the binding energies
associated with the noncovalent interactions observed in the crystal structures
were also evaluated. The study of the direct-current magnetic properties, as well
as ab initio calculations, reveal that both 1 and 2 present a strong easy-plane
magnetic anisotropy (D > 0), which is larger for the latter polymorph (D is found
to exhibit values between +58 and 117 cm(-1) depending on the method).
Alternating current dynamic susceptibility measurements show that these
polymorphs exhibit field-induced slow relaxation of the magnetization with Ueff
values of 19.5 and 21.1 cm(-1) for 1 and 2, respectively. The analysis of the
whole magnetic data allows the conclusion that the magnetization relaxation in
these polymorphs mainly takes place through a virtual excited state (Raman
process). It is worth noting that despite the notable difference between the
supramolecular networks of 1 and 2, they exhibit almost identical magnetization
dynamics. This fact suggests that the relaxation process is intramolecular in
nature and that the virtual state involved in the two-phonon Raman process lies
at a similar energy in polymorphs 1 and 2 (~20 cm(-1)). Interestingly, this value
is recurrent in Co(II) single-ion magnets, even for those displaying different
coordination number and geometry.
PMID- 27500423
TI - Selective Harvesting of Marginating-hepatic Leukocytes.
AB - Marginating-hepatic (MH) leukocytes (leukocytes adhering to the sinusoids of the
liver), were shown to exhibit unique composition and characteristics compared to
leukocytes of other immune compartments. Specifically, evidence suggests a
distinct pro- and anti-inflammatory profile of the MH-leukocyte population and
higher cytotoxicity of liver-specific NK cells (namely, pit cells) compared to
circulating or splenic immunocytes in both mice and rats. The method presented
herein enables selective harvesting of MH leukocytes by forced perfusion of the
liver in mice and rats. In contrast to other methods used to extract liver
leukocytes, including tissue grinding and biological degradation, this method
exclusively yields leukocytes from the liver sinusoids, uncontaminated by cells
from other liver compartments. In addition, the perfusion technique better
preserves the integrity and the physiological milieu of MH leukocytes, sparing
known physiological responses to tissue processing. As many circulating malignant
cells and infected cells are detained while passing through the liver sinusoids,
physically interacting with endothelial cells and resident leukocytes, the unique
MH leukocyte population is strategically located to interact, identify, and react
towards aberrant circulating cells. Thus, selective harvesting of MH-leukocytes
and their study under various conditions may advance our understanding of the
biological and clinical significance of MH leukocytes, specifically with respect
to circulating aberrant cells and liver-related diseases and cancer metastases.
PMID- 27500424
TI - Glycoproteomic Analysis of Malignant Ovarian Cancer Ascites Fluid Identifies
Unusual Glycopeptides.
AB - Ovarian cancer is a major cause of cancer mortality among women, largely due to
late diagnosis of advanced metastatic disease. More extensive molecular analysis
of metastatic ovarian cancer is needed to identify post-translational
modifications of proteins, especially glycosylation that is particularly
associated with metastatic disease to better understand the metastatic process
and identify potential therapeutic targets. Glycoproteins in ascites fluid were
enriched by affinity binding to lectins (ConA or WGA) and other affinity
matrices. Separate glycomic, proteomic, and glycopeptide analyses were performed.
Relative abundances of different N-glycan groups and proteins were identified
from ascites fluids and a serum control. Levels of biomarkers CA125, MUC1, and
fibronectin were also monitored in OC ascites samples by Western blot analysis. N
Glycan analysis of ascites fluids showed the presence of large, highly
fucosylated and sialylated complex and hybrid glycans, some of which were not
observed in normal serum. OC ascites glycoproteins, haptoglobin, fibronectin,
lumican, fibulin, hemopexin, ceruloplasmin, alpha-1-antitrypsin, and alpha-1
antichymotrypsin were more abundant in OC ascites or not present in serum control
samples. Further glycopeptide analysis of OC ascites identified N- and O-glycans
in clusterin, hemopexin, and fibulin glycopeptides, some of which are unusual and
may be important in OC metastasis.
PMID- 27500425
TI - Boronic Acid: A Bio-Inspired Strategy To Increase the Sensitivity and Selectivity
of Fluorescent NADH Probe.
AB - Fluorescent probes have emerged as an essential tool in the molecular recognition
events in biological systems; however, due to the complex structures of certain
biomolecules, it remains a challenge to design small-molecule fluorescent probes
with high sensitivity and selectivity. Inspired by the enzyme-catalyzed reaction
between biomolecule and probe, we present a novel combination-reaction two-step
sensing strategy to improve sensitivity and selectivity. Based on this strategy,
we successfully prepared a turn-on fluorescent reduced nicotinamide adenine
dinucleotide (NADH) probe, in which boronic acid was introduced to bind with NADH
and subsequently accelerate the sensing process. This probe shows remarkably
improved sensitivity (detection limit: 0.084 MUM) and selectivity to NADH in the
absence of any enzymes. In order to improve the practicality, the boronic acid
was further modified to change the measurement conditions from alkalescent (pH
9.5) to physiological environment (pH 7.4). Utilizing these probes, we not only
accurately quantified the NADH weight in a health care product but also evaluated
intracellular NADH levels in live cell imaging. Thus, these bio-inspired
fluorescent probes offer excellent tools for elucidating the roles of NADH in
biological systems as well as a practical strategy to develop future sensitive
and selective probes for complicated biomolecules.
PMID- 27500426
TI - What should we consider when applying termination of resuscitation rules?
PMID- 27500428
TI - Isolating Mesangiogenic Progenitor Cells (MPCs) from Human Bone Marrow.
AB - In a research study aimed to isolate human bone marrow (hBM)-derived Mesenchymal
Stromal Cells (MSCs) for clinical applications, we identified a novel cell
population specifically selected for growth in human serum supplemented medium.
These cells are characterized by morphological, phenotypic, and molecular
features distinct from MSCs and we named them Mesodermal Progenitor Cells (MPCs).
MPCs are round, with a thick highly refringent core region; they show strong,
trypsin resistant adherence to plastic. Failure to expand MPCs directly revealed
that they are slow in cycling. This is as also suggested by Ki-67 negativity. On
the other hand, culturing MPCs in standard medium designed for MSC expansion,
gave rise to a population of exponentially growing MSC-like cells. Besides
showing mesenchymal differentiation capacity MPCs retained angiogenic potential,
confirming their multiple lineage progenitor nature. Here we describe an
optimized highly reproducible protocol to isolate and characterize hBM-MPCs by
flow cytometry (CD73, CD90, CD31, and CD45), nestin expression, and F-actin
organization. Protocols for mesengenic and angiogenic differentiation of MPCs are
also provided. Here we also suggest a more appropriate nomenclature for these
cells, which has been re-named as "Mesangiogenic Progenitor Cells".
PMID- 27500427
TI - The Effectiveness and Long-Term Outcome of Conjunctivodacryocystorhinostomy With
Frosted Jones Tubes.
AB - PURPOSE: To describe success rates and long-term outcomes of
conjunctivodacryocystorhinostomy (CDCR) with frosted Jones tubes (FJT) for
epiphora with proximal outflow obstruction. METHODS: A retrospective chart review
of all patients undergoing external and endoscopic CDCR with FJTs by one author
(RAD) was performed between January 1, 2006 and November 1, 2014 at the Casey Eye
Institute. Patient demographics, etiology of tearing, concurrent endonasal and
eyelid procedures, and FJT size were recorded. After CDCR, follow-up time, tube
size changes, tube position, and tearing status were noted. Exclusion criteria
included follow up less than 6 months and/or prior CDCR. The study was IRB
approved, HIPAA compliant, and adherent to the declaration of Helsinki. RESULTS:
Forty-two eyes of 31 patients met the inclusion criteria, with the majority
having epiphora from canalicular obstruction (31%) or flaccid canaliculi (31%).
Average follow up was 1,088 days. Forty of 42 eyes, or 30 of 31 patients, had
complete resolution of tearing after surgery. Twenty of 42 eyes required tube
size changes, usually an increase in collar size (45%) and/or decrease in tube
length (55%). Six of 42 FJTs were lost, one migrating outward, with an average
time to loss between 61 and 1,122 days (mean 817 days). After collars larger than
4 mm became available, only one tube was lost. All epiphora resolved after repeat
CDCR. The most common complication was intermittent irritation (17%) near the FJT
that resolved after antibiotic-steroid drops and/or tube replacement/cleaning.
CONCLUSION: CDCR with FJTs is highly effective in correcting epiphora, and well
tolerated by the majority.
PMID- 27500429
TI - Achieving High-Energy-High-Power Density in a Flexible Quasi-Solid-State Sodium
Ion Capacitor.
AB - Simultaneous integration of high-energy output with high-power delivery is a
major challenge for electrochemical energy storage systems, limiting dual fine
attributes on a device. We introduce a quasi-solid-state sodium ion capacitor
(NIC) based on a battery type urchin-like Na2Ti3O7 anode and a capacitor type
peanut shell derived carbon cathode, using a sodium ion conducting gel polymer as
electrolyte, achieving high-energy-high-power characteristics in solid state.
Energy densities can reach 111.2 Wh kg(-1) at power density of 800 W kg(-1), and
33.2 Wh kg(-1) at power density of 11200 W kg(-1), which are among the best
reported state-of-the-art NICs. The designed device also exhibits long-term
cycling stability over 3000 cycles with capacity retention ~86%. Furthermore, we
demonstrate the assembly of a highly flexible quasi-solid-state NIC and it shows
no obvious capacity loss under different bending conditions.
PMID- 27500430
TI - Tenosynovitis of the Hand and Wrist: A Critical Analysis Review.
AB - Trigger FingerTrigger finger is common in patients with diabetes.Corticosteroid
injections are effective in about 60% to 92% of cases.Proximal interphalangeal
joint contracture may occur in long-standing cases.The outcomes of open and
percutaneous releases are similar; however, surgeons are split on preferences.
Intersection SyndromeThe classic finding is crepitus with wrist motion at the
distal one-third of the radial aspect of the forearm. Extensor Pollicis Longus
(EPL) TenosynovitisCorticosteroid injections should be used with caution because
of the potential for rupture.EPL tenosynovitis is very rare. de Quervain
DisorderThis condition is common in postpartum women.A positive Finkelstein test
is considered to be pathognomonic of de Quervain disorder, but care should be
taken to differentiate this condition from thumb carpometacarpal
arthritis.Corticosteroid injections are effective in about 80% of cases.Patients
in whom corticosteroid injections fail to provide relief of symptoms frequently
have a separate extensor pollicis brevis (EPB) compartment.The abductor pollicis
longus (APL) tendon has multiple slips; care should be taken not to confuse one
of these slips as the EPB.Traction on the APL pulls up the thumb metacarpal but
not the thumb tip.Traction on the EPB extends the thumb metacarpophalangeal
joint.Care should be taken to avoid injury to the sensory branch of the radial
nerve. Fourth Compartment TenosynovitisThis uncommon condition is most often seen
in patients with rheumatoid arthritis.The condition involves a large diffuse
area, as opposed to the compact dorsal ganglion cyst.
PMID- 27500431
TI - Blood Glucose Levels Following Intra-Articular Steroid Injections in Patients
with Diabetes: A Systematic Review.
AB - BACKGROUND: Parenterally administered steroids have been shown to affect the
metabolism of glucose and to cause abnormal blood glucose levels in diabetic
patients. These abnormal blood glucose levels in diabetic patients raise concerns
that intra-articular steroid injections also may affect blood glucose levels. We
performed a systematic review of studies examining the effect of intra-articular
steroid injections on blood glucose levels in patients with diabetes mellitus.
METHODS: A literature search of the PubMed, EMBASE, AMED, and CINAHL databases
using all relevant keywords and phrases revealed 532 manuscripts. After the
application of inclusion criteria, seven studies with a total of seventy-two
patients were analyzed. RESULTS: All studies showed a rise in blood glucose
levels following intra-articular steroid injection. Four of the seven studies
showed a substantial increase in blood glucose. Peak values reached as high as
500 mg/dL. The peak increase in blood glucose did not occur immediately following
intra-articular steroid injection, and in some cases it took several days to
occur. In many patients, post-injection hyperglycemia occurred within twenty-four
to seventy-two hours. CONCLUSION: Intra-articular steroid injections may cause
hyperglycemia in patients with diabetes mellitus, and patients should be warned
of this complication. Diabetic patients should be advised to regularly monitor
their blood glucose levels for up to a week after injection and should seek
medical advice if safe thresholds are breached. LEVEL OF EVIDENCE: Therapeutic
Level IV. See Instructions for Authors for a complete description of levels of
evidence.
PMID- 27500432
TI - Treatment of Head and Neck Injuries in the Helmeted Athlete.
AB - Sport-related concussion treatment includes three major phases: initial
evaluation at the time of the injury, treatment while the patient is symptomatic,
and evaluation of the readiness for a gradual return to participation. Each
concussion evaluation should include similar elements: assessment of symptoms,
assessment of cognitive ability, assessment of coordination (of the eyes, upper
extremities, and lower extremities), and assessment for additional injuries. The
spine-boarding recommendations from the American College of Emergency Physicians,
National Association of EMS Physicians, and National Athletic Trainers'
Association have changed. These recommendations include both decreased use of
spinal immobilization and removal of the helmet and shoulder pads prior to
securing the athlete to the board when sufficient numbers of trained providers
are present. Preseason training and pregame meetings or "medical time outs"
should become standard practice for the sidelines medical team (including the
athletic trainer, team physician, emergency response personnel, and possibly
others).
PMID- 27500433
TI - New Article Type for JBJS Reviews.
PMID- 27500434
TI - Nonsteroidal Anti-Inflammatory Drugs and Bone-Healing: A Systematic Review of
Research Quality.
AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often avoided by
orthopaedic surgeons because of their possible influence on bone-healing. This
belief stems from multiple studies, in particular animal studies, that show
delayed bone-healing or nonunions associated with NSAID exposure. The purpose of
this review was to critically analyze the quality of published literature that
evaluates the impact of NSAIDs on clinical bone-healing. METHODS: A MEDLINE and
Embase search was conducted to identify all articles relating to bone and
fracture-healing and the utilization of NSAIDs. All human studies, including
review articles, were identified for further analysis. Non-English-language
manuscripts and in vitro and animal studies were excluded. A total of twelve
clinical articles and twenty-four literature reviews were selected for analysis.
The quality of the clinical studies was assessed with a modified Coleman
Methodology Score with emphasis on the NSAID utilization. Review articles were
analyzed with regard to variability in the cited literature and final
conclusions. RESULTS: The mean modified Coleman Methodology Score (and standard
deviation) was significantly lower (p = 0.032) in clinical studies that
demonstrated a negative effect of NSAIDs on bone-healing (40.0 +/- 14.3 points)
compared with those that concluded that NSAIDs were safe (58.8 +/- 10.3 points).
Review articles also demonstrated substantial variability in the number of cited
clinical studies and overall conclusions. There were only two meta-analyses and
twenty-two narrative reviews. The mean number (and standard deviation) of
clinical studies cited was significantly greater (p = 0.008) for reviews that
concluded that NSAIDs were safe (8.0 +/- 4.8) compared with those that
recommended avoiding them (2.1 +/- 2.1). Unanimously, all reviews admitted to the
need for prospective randomized controlled trials to help clarify the effects of
NSAIDs on bone-healing. CONCLUSIONS: This systematic literature review highlights
the great variability in the interpretation of the literature addressing the
impact of NSAIDs on bone-healing. Unfortunately, there is no consensus regarding
the safety of NSAIDs following orthopaedic procedures, and future studies should
aim for appropriate methodological designs to help to clarify existing
discrepancies to improve the quality of care for orthopaedic patients. CLINICAL
RELEVANCE: This systematic review highlights the limitations in the current
understanding of the effects of NSAIDs on bone healing. Thus, withholding these
medications does not have any proven scientific benefit to patients and may even
cause harm by increasing narcotic requirements in cases in which they could be
beneficial for pain management. This review should encourage further basic
science and clinical studies to clarify the risks and benefits of anti
inflammatory medications in the postoperative period, with the aim of improving
patient outcomes.
PMID- 27500435
TI - Enhancement of Bone-Healing by Low-Intensity Pulsed Ultrasound: A Systematic
Review.
AB - BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is frequently used to enhance
or to accelerate fracture-healing, but its clinical role and effectiveness as a
treatment modality remain uncertain. We performed a systematic review and meta
analysis of randomized controlled trials to determine the efficiency of LIPUS on
bone-healing and/or fracture union, as well as on functional recovery. METHODS:
The databases of PubMed/MEDLINE, Cochrane Central Register of Controlled Trials,
CINAHL, Web of Science, and Embase were searched for trials concerning LIPUS
stimulation and bone-healing or fracture repair, in any language, published from
the inception of the database to January 2, 2015. Eligible studies were
randomized controlled trials that enrolled patients with any type of fracture,
delayed union, or nonunion and randomly assigned them to LIPUS treatment or a
control group. Two reviewers independently agreed on eligibility, assessed
methodological quality, and extracted outcome data. All relevant outcomes were
pooled, and a meta-analysis was performed. RESULTS: Twenty-four unique randomized
trials were selected for analysis after the search of all databases and the
inclusion of one trial by the senior author. Time to radiographic fracture union
was the most common primary outcome measure evaluated. After pooling the data
concerning time to radiographic healing in the combined patient population (n =
429), LIPUS treatment resulted in a mean reduction in healing time of 39.8 days
(95% confidence interval, 17.7 to 62.0 days; I = 94%). The most reduction in time
to radiographic union by LIPUS treatment was seen in fractures with a long
natural healing tendency. Three trials evaluating the time to return to work or
active duty, as a surrogate for functional recovery, were unable to demonstrate a
beneficial effect of LIPUS (n = 179). Evidence from two high-quality trials
implied that LIPUS enhances fracture-healing through increased bone formation in
cases of delayed and/or impaired bone-healing. The prevention of delayed union or
nonunion by LIPUS treatment could not be demonstrated. CONCLUSIONS: LIPUS
treatment effectively reduces the time to radiographic fracture union, but this
does not directly result in a beneficial effect of accelerated functional
recovery or the prevention of delayed union or nonunion. The increase in bone
formation as a result of LIPUS treatment may provide a valuable tool in fracture
repair, but it does not always lead to healing. Future studies should focus on
reporting of a combination of subjective signs of clinical healing, functional
recovery, and radiographic union to determine the effectiveness of LIPUS
treatment in clinical fracture-healing. LEVEL OF EVIDENCE: Therapeutic Level II.
See Instructions for Authors for a complete description of levels of evidence.
PMID- 27500436
TI - Recurrent Cubital Tunnel Syndrome: A Critical Analysis Review.
AB - Most patients (>90%) will have continued or recurrent symptoms after primary
cubital tunnel release. Those patients with severe preoperative findings are at a
higher risk of failure. Failed primary surgery may be due to diagnostic,
technical, or biologic factors. Revision surgical interventions can provide
relief, but there is no consensus on what is the optimal technique. The options
for revision surgery include simple neurolysis, neurolysis with subcutaneous
transposition, and neurolysis with submuscular transposition. Autogenous (vein)
and non-autogenous nerve wraps may be placed around the nerve to prevent cicatrix
reformation.
PMID- 27500437
TI - Cost-effectiveness analysis of therapeutic options for chronic hepatitis C
genotype 3 infected patients.
AB - BACKGROUND: This study provides a cost-effectiveness analysis of therapeutic
strategies for chronic hepatitis C genotype 3 infected patients in Spain.
METHODS: A Markov model was designed to simulate the progression in a cohort of
patients aged 50 years over a lifetime horizon. RESULTS: Sofosbuvir (SOF) plus
peginterferon and ribavirin for 12 weeks was a cost-effective option when
compared to standard of care (SoC) in the treatment of both 'moderate fibrosis'
and 'cirrhotic' patients. Incremental cost-effectiveness ratios were ?35,276/QALY
and ?18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens
versus SoC were over the threshold limit considered, at ?56,178/QALY and
?77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively.
CONCLUSION: Addition of SOF to IFN-based regimens for genotype 3 was cost
effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options
including SOF and DCV association required price reductions lower than the list
prices to be considered cost-effective.
PMID- 27500438
TI - All-inorganic perovskite CsPb(Br/I)3 nanorods for optoelectronic application.
AB - Halide perovskites have attracted great attention in recent years as promising
materials for optoelectronic devices, especially inorganic perovskites like
CsPbX3 (X = I, Br, Cl). Herein, CsPb(Br/I)3 nanorods with a photoluminescence
(PL) spectrum located at 610 nm have been obtained by a facile hot-injection
method, and the UV-vis absorption spectrum further revealed that the bandgap
absorption is around 1.98 eV. Furthermore, the photoelectric response of the
CsPb(Br/I)3 nanorods showed a relatively short rise-time (0.68 s) and decay-time
(0.66 s), and the on/off photocurrent ratio of the CsPb(Br/I)3 nanorod based
photodetector was up to 10(3).
PMID- 27500439
TI - On-line determination by small angle X-ray scattering of the shape of hen egg
white lysozyme immediately following elution from a hydrophobic interaction
chromatography column.
AB - This study documents the use of an integrated approach, involving on-line
hydrophobic interaction chromatography interfaced with Small Angle X-ray
Scattering (HIC-SAXS) measurements, to monitor the conformational status of
proteins immediately upon elution from a chromatographic column operated at
different temperatures. Moreover, this approach provides an additional avenue to
interrogate the changes in protein shape that may occur across the eluted
chromatographic peak. To this end, radii of gyration were extrapolated from the
Guinier approximation with the HIC-SAXS data, whilst pair distribution functions
and bead model simulations were generated by using the indirect transform program
GNOM and ab initio reconstruction with GASBOR to provide further insight into
protein conformational changes that occur during hydrophobic interaction
chromatography.
PMID- 27500440
TI - Hyperglycemia and outcomes in patients with sepsis.
PMID- 27500441
TI - Errata: Studies published in indexed journals on lawsuits for medicines in
Brazil: a systematic review.
AB - [This corrects the article DOI: 10.1590/0102-311X00219113.].
PMID- 27500442
TI - Ceritinib in second and further lines of therapy in advanced ALK mutant
adenocarcinoma.
PMID- 27500443
TI - Formation of Large Ag Clusters with Shells of Methane, Ethylene, and Acetylene in
He Droplets.
AB - Helium droplets were used to assemble composite metal-molecular clusters.
Produced clusters have several hundreds of silver atoms in the core, immersed in
a shell consisting of methane, ethylene, or acetylene molecules. The structure of
the clusters was studied via infrared spectra of the C-H stretches of the
hydrocarbon molecules. The spectra of the clusters containing methane and
acetylene show two distinct features due to molecules on the interface with
silver core and those in the volume of the neat molecular part of the clusters.
The relative intensities of the peaks are in good agreement with the estimates
based on the number of the captured particles. Experiments also suggest that
selection rules for infrared transitions for molecules adsorbed on metal surfaces
are also valid for silver clusters as small as 300 atoms.
PMID- 27500444
TI - MicroRNAs are key regulators of hepatocellular carcinoma (HCC) cell dissemination
what we learned from microRNA-494.
PMID- 27500445
TI - Protocol for the Direct Conversion of Murine Embryonic Fibroblasts into
Trophoblast Stem Cells.
AB - Trophoblast stem cells (TSCs) arise as a consequence of the first cell fate
decision in mammalian development. They can be cultured in vitro, retaining the
ability to self-renew and to differentiate into all subtypes of the trophoblast
lineage, equivalent to the in vivo stem cell population giving rise to the fetal
portion of the placenta. Therefore, TSCs offer a unique model to study placental
development and embryonic versus extra-embryonic cell fate decision in vitro.
From the blastocyst stage onwards, a distinct epigenetic barrier consisting of
DNA methylation and histone modifications tightly separates both lineages. Here,
we describe a protocol to fully overcome this lineage barrier by transient over
expression of trophoblast key regulators Tfap2c, Gata3, Eomes and Ets2 in murine
embryonic fibroblasts. The induced trophoblast stem cells are able to self-renew
and are almost identical to blastocyst derived trophoblast stem cells in terms of
morphology, marker gene expression and methylation pattern. Functional in vitro
and in vivo assays confirm that these cells are able to differentiate along the
trophoblast lineage generating polyploid trophoblast giant cells and chimerizing
the placenta when injected into blastocysts. The induction of trophoblast stem
cells from somatic tissue opens new avenues to study genetic and epigenetic
characteristics of this extra-embryonic lineage and offers the possibility to
generate trophoblast stem cell lines without destroying the respective embryo.
PMID- 27500446
TI - Development of an Algorithm to Perform a Comprehensive Study of Autonomic
Dysreflexia in Animals with High Spinal Cord Injury Using a Telemetry Device.
AB - Spinal cord injury (SCI) is a debilitating neurological condition characterized
by somatic and autonomic dysfunctions. In particular, SCI above the mid-thoracic
level can lead to a potentially life-threatening hypertensive condition called
autonomic dysreflexia (AD) that is often triggered by noxious or non-noxious
somatic or visceral stimuli below the level of injury. One of the most common
triggers of AD is the distension of pelvic viscera, such as during bladder and
bowel distension or evacuation. This protocol presents a novel pattern
recognition algorithm developed for a JAVA platform software to study the
fluctuations of cardiovascular parameters as well as the number, severity and
duration of spontaneously occurring AD events. The software is able to apply a
pattern recognition algorithm on hemodynamic data such as systolic blood pressure
(SBP) and heart rate (HR) extracted from telemetry recordings of conscious and
unrestrained animals before and after thoracic (T3) complete transection. With
this software, hemodynamic parameters and episodes of AD are able to be detected
and analyzed with minimal experimenter bias.
PMID- 27500447
TI - Bracing the trunk and neck in young adults leads to a more aged-like gait.
AB - Older individuals typically walk at slower speeds, with shorter step lengths,
greater step widths and spend a larger proportion of the gait cycle in double
stance. Changes in neck and trunk mobility may underlie some of the changes in
walking seen with increasing age. Consequently, this study was designed to assess
whether externally increasing trunk/neck stiffness in young adults leads to
similar changes in gait pattern observed with aging. Twelve young adults (20-29
years), sixteen old adults (60-69 years) and fifteen older adults (70-79 years)
walked across a 20' pressure sensitive GAITRite(c) instrumented walkway at their
preferred speed. The young adults also walked under three bracing conditions: (1)
Neck braced, (2) Trunk braced, and (3) Neck and Trunk braced. The results
revealed that the old and older age groups walked significantly slower, with a
shorter step length and with a narrower base of support (p's<0.05) compared to
the young adults. In young adults, combined neck and trunk bracing led to reduced
walking speed, shorter step length, wider base of support and a larger proportion
of the gait cycle spent in double stance (p's<0.05). The walking speed and step
length of older adults remained less than fully braced young adults (p's<0.05).
Overall these results indicate that artificially stiffening the trunk and neck of
young individuals leads to systematic gait changes similar to aging.
Consequently, age-related changes in mobility of the neck and torso may in part
contribute to the decrements in walking seen for older adults.
PMID- 27500448
TI - Relationship between fluoride exposure and osteoclast markers during RANKL
induced osteoclast differentiation.
AB - Skeletal fluorosis is a metabolic bone disease caused by excessive accumulation
of fluoride. Although the cause of this disease is known, the mechanism by which
fluoride accumulates on the bone has not been clearly defined, thus there are no
markers that can be used for screening skeletal fluorosis in epidemiology. In
this study, osteoclasts were formed from bone marrow cells of C57BL/6 mice
treated with macrophage colony stimulating factor and receptor activator of
nuclear factor kappa-B ligand. The mRNA expression of tartrate-resistant acid
phosphatase 5b (TRAP5b), osteoclast-associated receptor (OSCAR), calcitonin
receptor (CTR), matrix metalloproteinase 9 (MMP9) and cathepsin K (CK) were
detected using real-time PCR (RT-PCR). Results showed that fluoride between 0.5
and 8mg/l had no effect on osteoclast formation. However fluoride at 0.5mg/l
level significantly decreased the activity of osteoclast bone resorption.
Fluoride concentration was negatively correlated with the activity of osteoclast
bone resorption. On day 5 of osteoclast differentiation maturity, MMP9 and CK
mRNA expression were not only negatively correlated with fluoride concentration,
but directly correlated with the activity of osteoclast bone resorption. TRAP5b,
CTR and OSCAR mRNA expression were positively correlated with the number of
osteoclast and they had no correlation with the activity of osteoclast bone
resorption. Thus, it can be seen that MMP9 and CK may reflect the change of
activity of bone resorption as well the degree of fluoride exposure. TRAP5b, CTR
and OSCAR can represent the change of number of osteoclast formed.
PMID- 27500449
TI - Advanced Compositional Analysis of Nanoparticle-polymer Composites Using Direct
Fluorescence Imaging.
AB - The fabrication of polymer-nanoparticle composites is extremely important in the
development of many functional materials. Identifying the precise composition of
these materials is essential, especially in the design of surface catalysts,
where the surface concentration of the active component determines the activity
of the material. Antimicrobial materials which utilize nanoparticles are a
particular focus of this technology. Recently swell encapsulation has emerged as
a technique for inserting antimicrobial nanoparticles into a host polymer matrix.
Swell encapsulation provides the advantage of localizing the incorporation to the
external surfaces of materials, which act as the active sites of these materials.
However, quantification of this nanoparticle uptake is challenging. Previous
studies explore the link between antimicrobial activity and surface concentration
of the active component, but this is not directly visualized. Here we show a
reliable method to monitor the incorporation of nanoparticles into a polymer host
matrix via swell encapsulation. We show that the surface concentration of
CdSe/ZnS nanoparticles can be accurately visualized through cross-sectional
fluorescence imaging. Using this method, we can quantify the uptake of
nanoparticles via swell encapsulation and measure the surface concentration of
encapsulated particles, which is key in optimizing the activity of functional
materials.
PMID- 27500450
TI - Hand-held dynamometry strength measures for internal and external rotation
demonstrate superior reliability, lower minimal detectable change and higher
correlation to isokinetic dynamometry than externally-fixed dynamometry of the
shoulder.
AB - OBJECTIVES: To investigate inter and intra-rater reliability of hand held (HHD)
and externally fixed (EFD) dynamometry for shoulder internal (IR) and external
rotation (ER) strength and their correlation to isokinetic testing. DESIGN:
Within participant, inter and intra-rater reliability study. PARTICIPANTS: Twenty
active, healthy male and female participants underwent testing by two examiners.
OUTCOME MEASURES: Intra-class coefficients (ICC), percentage standard error of
measurement (%SEM), and percentage minimal detectable change (%MDC) were
calculated for inter-rater, intra-day and intra-rater, inter-week reliability.
Maximum and average of three repetitions were compared to the isokinetic results
at three speeds (60 degrees /sec, 180 degrees /sec, 240 degrees /sec) for both
concentric and eccentric contractions. RESULTS: Inter and intra-tester values
demonstrated good to high agreement (HHD, ICC range = 0.89-0.97, %SEM = 4.80
8.60%, %MDC = 13.29-23.70%; EFD, ICC = 0.88-0.96, %SEM = 6.60-11.00%, %MDC =
18.40-30.04%). HHD and EFD showed moderate to very strong correlations to the
isokinetic testing (HHD, r = 0.45-0.86; EFD, r = 0.49-0.83). CONCLUSIONS: The
results of this study indicate that both EFD and HHD are suitable for clinical
practice and research. Hand-held dynamometry is preferred due to its higher intra
and inter-rater reliability and smaller MDC and lower SEM.
PMID- 27500451
TI - Thulium Laser Resection Versus Plasmakinetic Resection of Prostates in the
Treatment of Benign Prostate Hyperplasia: A Meta-Analysis.
AB - OBJECTIVES: To compare the safety and efficacy of thulium laser resection of
prostate (ThuRP) and plasmakinetic resection of prostate (PKRP) for benign
prostate hyperplasia (BPH), we made this meta-analysis in regard of the two
techniques. METHODS: A systematic search of PubMed, Web of Science, and China
National Knowledge Infrastructure was performed up to October 1, 2015. Outcomes
of interest assessing the two techniques included demographic and clinical
characteristics, perioperative variables, follow-up data, and complications.
RESULTS: Nine eligible trials evaluating ThuRP versus PKRP for BPH were
identified, including six randomized controlled trials (RCTs) and three
retrospective trials. ThuRP was associated with longer operation time (P < .001),
shorter hospital stay (P < .001), irrigation (P = .02), and catheterization (P <
.001) duration. Estimated blood loss (P = .005) and drop in hemoglobin level (P =
.02) were significantly more in PKRP. Except quality of life score (P = .04),
which was better in ThuRP, the postoperative data, including international
prostate symptom score (P = .44), Qmax (P = .33), postvoid residual urine volume
(P = .55), and the complications such as severe bleeding (P = .52), temporary
urinary retention (P = .20), temporary urinary incontinence (P = .64), urinary
tract infection (P = .83), and urethral stricture (P = .22), did not differ
significantly. CONCLUSION: Our analysis showed that there was no significant
difference in terms of efficacy between ThuRP and PKRP. Although ThuRP was
associated with longer operation time, it possessed more safe capacity with less
blood loss, shorter hospital stay, irrigation, and catheterization duration. More
worldwide RCTs with long-term follow-up are still needed to support our
conclusion.
PMID- 27500452
TI - Decreased functional connectivity to posterior cingulate cortex in major
depressive disorder.
AB - The default mode network (DMN) and its interaction with other key networks such
as the salience network and executive network are keys to understand psychiatric
and neurological disorders including major depressive disorder (MDD). In this
study, we combined independent component analysis and seed based connectivity
analysis to study the posterior default mode network between 20 patients with MDD
and 25 normal controls, as well as pre-treatment and post-treatment conditions of
the patients. Both correlated and anti-correlated networks centered at the
posterior cingulate cortex (PCC) were examined (PCC+ and PCC-). Our results
showed aberrant functional connectivity of the PCC+ and PCC- networks between
patients and normal controls. Specifically, normal controls exhibited
significantly higher connectivity between the PCC and frontal/temporal regions
for the PCC+ network and stronger connectivity strength between the PCC and the
insula/middle frontal cortex for the PCC- network. The overall connectivity
strength of the PCC+ and PCC- networks was also significantly lower in MDD.
Because the PCC is a hub in the DMN that interacts with other networks, our
result suggested a stronger interaction between the DMN and the salience network
but a weak interaction between the DMN and the executive network in MDD. The
treatment using sertraline did increase the functional connectivity strength,
especially in the PCC+ network. Despite a large inter-subject variability in the
overall connectivity strengths and change of the PCC network in response to the
treatment, a high correlation between change of connectivity strength and the
Hamilton depression score was observed for both the PCC+ and PCC- network.
PMID- 27500454
TI - The use of beached bird surveys for marine plastic litter monitoring in Ireland.
AB - Marine plastic litter has become a major threat to wildlife. Marine animals are
highly susceptible to entanglement and ingestion of debris at sea. Governments
all around the world are being urged to monitor litter sources and inputs, and to
mitigate the impacts of marine litter, which is primarily composed of plastics.
European policies, such as Oslo-Paris Convention (OSPAR) and Marine Strategy
Framework Directive (MSFD) have adopted the monitoring of a seabird species, the
Northern Fulmar (Fulmarus glacialis), as an environmental quality indicator
through the analysis of stomach contents of beached Fulmar specimens. The aims of
this research were to: firstly set a baseline investigation of multispecies of
seabirds in Ireland affected by the ingestion of litter and, secondly to
investigate the feasibility of using Fulmar and/or other potential species of
seabird as an indicator for marine debris in Ireland through beached bird
surveys. Within 30 months, 121 birds comprising 16 different species were
collected and examined for the presence of litter. Of these, 27.3% (n = 33)
comprising 12 different species were found to ingest litter, mainly plastics. The
average mass of ingested litter was 0.141 g. Among 14 sampled Northern Fulmars,
13 (93%) had ingested plastic litter, all of them over the 0.1 g threshold used
in OSPAR and MSFD policy target definitions. Results show that seabirds in
Ireland are ingesting marine litter, as in many other countries in the world.
Monitoring seabird litter ingestion has the potential to form part of a wider
marine litter monitoring programme that can help to inform mitigation and
management measures for marine litter.
PMID- 27500453
TI - Lifetime use of cannabis from longitudinal assessments, cannabinoid receptor
(CNR1) variation, and reduced volume of the right anterior cingulate.
AB - Lifetime measures of cannabis use and co-occurring exposures were obtained from a
longitudinal cohort followed an average of 13 years at the time they received a
structural MRI scan. MRI scans were analyzed for 88 participants (mean age=25.9
years), 34 of whom were regular users of cannabis. Whole brain voxel based
morphometry analyses (SPM8) were conducted using 50 voxel clusters at p=0.005.
Controlling for age, familial risk, and gender, we found reduced volume in
Regular Users compared to Non-Users, in the lingual gyrus, anterior cingulum
(right and left), and the rolandic operculum (right). The right anterior cingulum
reached family-wise error statistical significance at p=0.001, controlling for
personal lifetime use of alcohol and cigarettes and any prenatal exposures. CNR1
haplotypes were formed from four CNR1 SNPs (rs806368, rs1049353, rs2023239, and
rs6454674) and tested with level of cannabis exposure to assess their interactive
effects on the lingual gyrus, cingulum (right and left) and rolandic operculum,
regions showing cannabis exposure effects in the SPM8 analyses. These analyses
used mixed model analyses (SPSS) to control for multiple potentially confounding
variables. Level of cannabis exposure was associated with decreased volume of the
right anterior cingulum and showed interaction effects with haplotype variation.
PMID- 27500455
TI - Prevalence and risk factors of poor sleep quality among Inner Mongolia Medical
University students: A cross-sectional survey.
AB - Medical students face new challenges at the beginning of college life, such as
being responsible for oneself, an unfamiliar environment, social obligations, and
academic stress, all of which influence or even heavily change their sleep
quality and life, leading to sleep-related problems to some degree. This study
investigated the relationship between sleep quality and behavior among students
at the Inner Mongolia Medical University in China. Self-administered
questionnaires were used to collect information on sociodemographic
characteristics and lifestyle habits. The Pittsburgh Sleep Quality Index was also
used. A total of 6044 and 6085 students completed the questionnaires in 2011 and
2013. According to the index, 27.8% (1694) of students had poor sleep quality
with major risk factors being poor academic performance and interpersonal
relationships in 2013. Among others, regular exercise less than three times a
week, skipping breakfast, and studying in higher grades were associated with poor
sleep quality. These results will help university administrators understand the
risk factors of poor sleep quality among students, which can be improved through
individual efforts, and provide adequate counseling and systematic education to
improve their behavior and lifestyle.
PMID- 27500456
TI - Prevalence, correlates, psychiatric comorbidities, and suicidality in a community
population with problematic Internet use.
AB - We examined the prevalence, correlates, and psychiatric comorbidities of
community-dwelling subjects with problematic Internet use (PIU). In an
epidemiological survey of mental disorders among Korean adults conducted in 2006,
6510 subjects (aged 18-64 years) completed the Korean version of the Composite
International Diagnostic Interview for DSM-IV psychiatric disorders; Diagnostic
Interview Schedule exploring pathological gambling; Adult ADHD Self-Report Scale
Version 1.1 Screener; questionnaire for sleep disturbances; and questionnaire for
suicidal ideations, plans, and attempts. Young's Internet Addiction Test was
administered to 3212 individuals who had used the Internet within one month
before the interviews in order to identify problematic Internet users (cutoff
>39). The prevalence of PIU was 9.3% in the general population of South Korea.
Being male, younger, never married, or unemployed were all associated with
increased risks of PIU. Significant positive associations were observed between
PIU and nicotine use disorders, alcohol use disorders, mood disorders, anxiety
disorders, somatoform disorders, pathological gambling, adult type ADHD symptoms,
sleep disturbances, suicide ideas and suicide plans compare to subjects without
PIU, after controlling for socio-demographic variables. These findings suggest
that careful evaluation and management of such psychiatric disorders is needed
for individuals with PIU.
PMID- 27500457
TI - Bendamustine increases interleukin-10 secretion from B cells via p38 MAP kinase
activation.
AB - We investigated the effects of bendamustine on B cell functions and explored
potential clinical applications of the drugs to autoimmune diseases.
Proliferation of Ramos cells, a human B cell line, was significantly inhibited by
25-100MUM of bendamustine in a dose-dependent manner. Concordantly, IgM secretion
from Ramos cells was significantly inhibited at these concentrations by up to
70%. Interestingly, however, the production and secretion of interleukin-10 (IL
10) were dramatically (at least >10-fold) increased by bendamustine at growth
inhibitory concentrations. Exploration of the molecular mechanism of IL-10
production revealed that bendamustine enhanced the phosphorylation of p38 MAP
kinase. Further, Sp1 was identified as a downstream transcription factor, and the
inhibition of p38 MAP kinase and Sp1 with their inhibitors led to the abrogation
of bendamustine-induced IL-10 production and the DNA binding of Sp1. Importantly,
when PBMC from healthy donors were cultured with bendamustine at the
concentration of 30MUM, under the stimulation with an anti-IgM antibody, an anti
CD40 antibody, recombinant human IL-21 (rhIL-21) and recombinant human soluble
BAFF (rhsBAFF), IL-10 production by B cells (CD20+CD4-CD8-CD14-) among peripheral
blood mononuclear cell (PBMC) was significantly enhanced by adding bendamustine.
These results collectively suggest that the p38 MAP kinase-Sp1 pathway plays a
crucial role in bendamustine-induced IL-10 production by B cells. Our findings
suggest a novel therapeutic possibility for autoimmune diseases through the
upregulation of IL-10 which has an anti-inflammatory effects.
PMID- 27500458
TI - Active hexose correlated compound modulates LPS-induced hypotension and gut
injury in rats.
AB - We hypothesized that AHCC; (Amino UP Chemical Co., Ltd., Sapporo, Japan), a
mushroom mycelium extract obtained from liquid culture of Lentinula edodes,
restores immune function in LPS-induced inflammation in the gut, especially when
the nitric oxide signaling pathway is impaired. This is the first inter
disciplinary proposal to identify molecular mechanisms involved in LPS-induced
immune dysfunction in the gut in conscious animals treated or non-treated with
AHCC, a promoter of immune support. Specifically, we have tested the effects of
AHCC on LPS-induced deleterious effects on blood pressure and gut injury in
conscious rats. The time course of biological markers of innate/acquired immune
responses, and inflammation/oxidative stress is fully described in the present
manuscript. Rats were randomly assigned into 3 groups (N=6 per group). Group 1
received 10% of AHCC in drinking water for 5days; Group 2 received
lipopolysaccharide (LPS; Escherichia coli 0111:B4 purchased from Sigma) only at
20mg/kg IV; Group 3 received combined treatments (AHCC + LPS). LPS was
administered at 20mg/kg IV, 5days following AHCC treatment. We have demonstrated
that AHCC decreased the LPS-deleterious effects of blood pressure and also
decreased inflammatory markers e.g., cytokines, nitric oxide and edema formation.
Finally, AHCC diminished lymphocyte infiltration, restoring gut architecture.
Because AHCC was administered prior to LPS, our results indicate the potential
impact of AHCC's prophylactic effects on LPS inflammation. Consequently,
additional experiments are warrant to assess its therapeutic effects in sepsis
induced inflammation.
PMID- 27500459
TI - Treatment with NAD(+) inhibited experimental autoimmune encephalomyelitis by
activating AMPK/SIRT1 signaling pathway and modulating Th1/Th17 immune responses
in mice.
AB - Nicotinamide adenine dinucleotide (NAD(+)) plays vital roles in mitochondrial
functions, cellular energy metabolism and calcium homeostasis. In this study, we
investigated the effect of NAD(+) administration for the treatment of
experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. EAE, a classical
animal model of multiple sclerosis (MS), was induced by subcutaneous injection of
myelin oligodendrocyteglycoprotein (MOG). The mice were treated with 250mg/kg
(body weight) NAD(+) in PBS administered intraperitoneally once daily. We
observed that NAD(+) treatment could lessen the severity of EAE. Additionally,
NAD(+) treatment attenuated pathological injuries of EAE mice. We also found that
the AMP-activated protein kinase (AMPK)/silent mating-type information regulation
2 homolog 1(SIRT1) pathway was activated in the NAD(+)-treated mice and NAD(+)
treatment suppressed pro-inflammatory T cell responses. Our findings demonstrated
that NAD(+) could be an effective and promising agent to treat multiple sclerosis
and its effects on other autoimmune diseases should be explored.
PMID- 27500460
TI - Tertiary Element Interaction in HIV-1 TAR.
AB - HIV-1 replication requires binding to occur between Trans-activation Response
Element (TAR) RNA and the TAT protein. This TAR-TAT binding depends on the
conformation of TAR, and therapeutic development has attempted to exploit this
dynamic behavior. Here we simulate TAR dynamics in the context of mutations
inhibiting TAR binding. We find that two tertiary elements, the apical loop and
the bulge, can interact directly, and this interaction may be linked to the
affinity of TAR for TAT.
PMID- 27500461
TI - Development of a High-Affinity PET Radioligand for Imaging Cannabinoid Subtype 2
Receptor.
AB - Cannabinoid receptors type 2 (CB2) represent a target with increasing importance
for neuroimaging due to its upregulation under various pathological conditions.
Encouraged by preliminary results obtained with [(11)C](Z)-N-(3-(2-methoxyethyl)
4,5-dimethylthiazol-2(3H)-ylidene)-2,2,3,3-tetramethyl-cyclopropanecarboxamide
([(11)C]A-836339, [(11)C]1) in a mouse model of acute neuroinflammation (induced
by lipopolysaccharide, LPS), we designed a library of fluorinated analogues
aiming for an [(18)F]-labeled radiotracer with improved CB2 binding affinity and
selectivity. Compound (Z)-N-(3-(4-fluorobutyl)-4,5-dimethylthiazol-2(3H)-ylidene)
2,2,3,3-tetramethyl-cyclopropanecarboxamide (29) was selected as the ligand with
the highest CB2 affinity (Ki = 0.39 nM) and selectivity over those of CB1 (factor
of 1000). [(18)F]29 was prepared starting from the bromo precursor (53). Specific
binding was shown in vitro, whereas fast metabolism was observed in vivo in CD-1
mice. Animal PET revealed a brain uptake comparable to that of [(11)C]1. In the
LPS-treated mice, a 20-30% higher uptake in brain was found in comparison to that
in nontreated mice (n = 3, P < 0.05).
PMID- 27500462
TI - Comparison Study of the Photoelectrochemical Activity of Carbon Nitride with
Different Photoelectrode Configurations.
AB - Polymeric carbon nitride (CN) has recently emerged as a novel metal-free
semiconductor due to its unique electronic structure, wide availability, and
promising applications in photoelectrochemical solar energy conversion. However,
few works regarding CN photoelectrode optimization such as by minimization of
unwanted grain boundary effects have been reported, which would greatly influence
the photoelectrochemcial conversion efficiency. Herein, three general ways of
preparing CN photoelectrode are presented and compared, including drop-casting of
CN particles, or further blendeding with Nafion or PEDOT-PSS as the binder. In
addition, the influences of CN particle sizes (0.5, 1.1, and 3.2 MUm) and the
film thickness (i.e., the loading amount) to the overall photoelectrochemcial
activity were also evaluated in detail. As a result, when PEDOT-PSS acted as
binder, CN particles with size of 0.5 MUm and an optimal loading amount (2.4
mg/cm(2)) were adopted; the as-prepared CN photoelectrode had much superior
photoelectrochemical activity than all other counterparts. Therefore, this study
would pave the way for preparing CN photoelectrode of superior quality so as to
promote CN materials to be better applied in solar fuel and sensing applications.
PMID- 27500463
TI - Upper motor neuron evaluation in multiple sclerosis patients treated with
Sativex(r).
AB - BACKGROUND: Spasticity in multiple sclerosis (MS) results from an imbalance of
inputs from descending pathways to the spinal motor circuits, as well as from a
damage of the corticospinal tract (CST). OBJECTIVES: To assess CST impairment in
MS patients with and without spasticity and to evaluate its evolution under
Sativex(r) treatment. METHODS: Ten MS patients with spasticity ("cases")
underwent clinical (EDSS, 9-hole Peg, Ashworth scale, Timed 25-Foot Walk, and NRS
for spasticity), MRI (CST fractional anisotropy [FA]), and electrophysiological
(central motor conduction time [CMCT] and H/M ratio) evaluations at baseline and
after 12 months. We selected 20 MS patients without spasticity as control group
at baseline. RESULTS: At baseline, cases showed a lower CST FA (0.492+/-0.045 vs
0.543+/-0.047; P=.01) and a higher CMCT (P=.001) compared to the control group.
No correlations were found between clinical, electrophysiological, and MRI
features. After 12 months, cases showed a decrease in non-prevalent degree of
impairment (PDI) side FA (0.502+/-0.023 vs 0.516+/-0.033; P=.01) without
differences for electrophysiological features compared to baseline. Treatment
with Sativex(r) resulted in a reduction of NRS for spasticity (P=.01).
CONCLUSIONS: We confirm the presence of CST impairment in MS patients with
spasticity. We did not identify structural/electrophysiological correlates that
could explain Sativex(r) clinical effect.
PMID- 27500464
TI - Incidence and Burden of Wheezing Disorders, Eczema, and Rhinitis in Children:
findings from the Born in Bradford Cohort.
AB - BACKGROUND: Bradford city has high infant mortality and there is a major health
concern in the community due to environmental pollution. The aim of the study was
to investigate the incidence and burden of wheezing disorders, eczema, and
rhinitis in children aged 3-7 years . METHODS: It is a prospective cohort study;
the participants were 13 734 children from the Born in Bradford cohort. RESULTS:
There were a total of 22.1% (95% Confidence Interval (CI) 21.4, 22.8%), 52.4%
(95% CI 51.5%, 53.2%), and 19.3% (95% CI 18.6, 19.9%) incidence cases of wheezing
disorders, eczema, and rhinitis respectively. A total of 37% (95% CI 36.2%,
37.8%), 19.5% (95% CI 18.9%, 20.2%,) and 5.9% (95% CI 5.5%, 6.3%) of the children
were affected by only one, two, and three diseases respectively. Boys to girls
incidence rate ratios for wheezing disorders, eczema, and rhinitis was 1.41 (95%
CI 1.31, 1.51), 1.02 (95% CI 0.97, 1.07), and 1.18 (95% CI 1.09, 1.28)
respectively. The respective incidence rate ratios of Pakistani to White British
were 0.94 (95% CI 0.87, 1.02), 1.31 (95% CI 1.24, 1.39), and 2.03 (95% CI 1.83,
2.25) respectively. CONCLUSION: This study shows that the burden of wheezing
disorders, eczema, and rhinitis in this cohort is higher than previously reported
in earlier studies. In addition, it indicates that while boys are more likely to
suffer from wheezing disorders, rhinitis, and multiple diseases than girls,
Pakistani children are more likely to suffer from eczema, rhinitis, and multiple
diseases than White British children.
PMID- 27500465
TI - The Predictive Role of the Neutrophil/Lymphocyte Ratio in Survival with Multiple
Myeloma: A Single Center Experience.
AB - BACKGROUND: Recent studies have shown a positive correlation between tumor
related immune response markers and the poor outcome in solid tumors. In this
study, we aimed to investigate the neutrophil/lymphocyte ratio (NLR) in multiple
myeloma. To the best of our knowledge, this would be the second report concerning
this topic. METHODS: We retrospectively reviewed the data for 52 multiple myeloma
patients. The patients were grouped using the baseline NLR as NLR <= 1.72 and NLR
> 1.72 using receiver operating characteristic analysis to determine a cut off.
We compared the two groups in terms of both the known prognostic factors of the
myeloma and the overall survival (OS). RESULTS: Our study showed that NLR is
associated with C-reactive protein and beta2 microglobulin (P = 0.02 and P =
0.001, respectively). The patients with NLR > 1.72 had significantly worse
stages, performance status, and kidney functions. The whole group's OS was
estimated as 35.1 months while the patients with lower NLR had better OS when
compared with those with NLR > 1.72 (42.75 and 26.14 months, respectively, P:
0.04). CONCLUSION: Neutrophil/lymphocyte ratio, which is associated with stage,
performance status, and kidney functions, can be used in daily practice as a
predictor for survival in multiple myeloma. Simply adding NLR to the routine
charts may enrich our data for larger studies.
PMID- 27500466
TI - Photon Upconversion at Crystalline Organic-Organic Heterojunctions.
AB - Triplet transfer across a surface-anchored metal-organic-framework heterojunction
is demonstrated by the observation of triplet-triplet annihilation photon
upconversion in a sensitizer-emitter heterostructure. Upconversion thresholds
under 1 mW cm-2 are achieved. In the broader context, the double-electron
exchange mechanism of triplet transfer indicates that the heterojunction quality
is sufficient for electrons to move between layers in this solution-processed
crystalline heterostructure.
PMID- 27500467
TI - Correlation between the presence of degenerated inclusion-bearing cells in voided
urine samples and the occurrence of polyomavirus infection.
AB - OBJECTIVE: The purpose of the present, prospective, cohort study was to monitor
urine cytology samples from recipients of renal transplants to search for the
occurrence of decoy cells and degenerated inclusion-bearing cells with an aim to
correlate the existence of these cells with molecular detection of polyomavirus
BK (BKV) DNA in urine. MATERIAL AND METHODS: This study included patients who
underwent renal transplantation. Patients had their urine tested quarterly,
during the first year post-transplantation, for the presence of decoy cells and
degenerated cells, as well as by quantitative determination of BKV load in the
urine and plasma. RESULTS: Three hundred and sixty-one examinations were
performed on 101 patients within 12 months of attendance. Urine cytology results
were: 198 (54.9%) negative and 60 (16.6%) positive for the presence of viral
cytopathic effects depending on the presence of BKV infection, 72 (19.9%)
positive for the manifestation of degenerated cells and 31 (8.6%) unsatisfactory
for analysis. There was a subtle tendency towards the presence of degenerated
inclusion-bearing cells in cases in which the virus was detected in voided urine.
However, the presence of degenerated cells exhibited a tendency to BKV positivity
in months 3, 6 and 9 and, exclusively in month 12, this trend was statistically
significant. CONCLUSIONS: There were not enough strong morphological and staining
elements to state the origin of the degenerated cells or to describe the nature
of the infection (viral or bacterial), given that these cells were undergoing an
apoptotic process in post renal transplant patients.
PMID- 27500468
TI - Melatonin as an antioxidant: under promises but over delivers.
AB - Melatonin is uncommonly effective in reducing oxidative stress under a remarkably
large number of circumstances. It achieves this action via a variety of means:
direct detoxification of reactive oxygen and reactive nitrogen species and
indirectly by stimulating antioxidant enzymes while suppressing the activity of
pro-oxidant enzymes. In addition to these well-described actions, melatonin also
reportedly chelates transition metals, which are involved in the Fenton/Haber
Weiss reactions; in doing so, melatonin reduces the formation of the
devastatingly toxic hydroxyl radical resulting in the reduction of oxidative
stress. Melatonin's ubiquitous but unequal intracellular distribution, including
its high concentrations in mitochondria, likely aid in its capacity to resist
oxidative stress and cellular apoptosis. There is credible evidence to suggest
that melatonin should be classified as a mitochondria-targeted antioxidant.
Melatonin's capacity to prevent oxidative damage and the associated physiological
debilitation is well documented in numerous experimental ischemia/reperfusion
(hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart
(heart attack). Melatonin, via its antiradical mechanisms, also reduces the
toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse.
Experimental findings also indicate that melatonin renders treatment-resistant
cancers sensitive to various therapeutic agents and may be useful, due to its
multiple antioxidant actions, in especially delaying and perhaps treating a
variety of age-related diseases and dehumanizing conditions. Melatonin has been
effectively used to combat oxidative stress, inflammation and cellular apoptosis
and to restore tissue function in a number of human trials; its efficacy supports
its more extensive use in a wider variety of human studies. The uncommonly high
safety profile of melatonin also bolsters this conclusion. It is the current
feeling of the authors that, in view of the widely diverse beneficial functions
that have been reported for melatonin, these may be merely epiphenomena of the
more fundamental, yet-to-be identified basic action(s) of this ancient molecule.
PMID- 27500469
TI - Insurance status, health equity, and the cancer care continuum.
PMID- 27500471
TI - Measurement of Survival Time in Brachionus Rotifers: Synchronization of Maternal
Conditions.
AB - Rotifers are microscopic cosmopolitan zooplankton used as models in
ecotoxicological and aging studies due to their several advantages such as short
lifespan, ease of culture, and parthenogenesis that enables clonal culture.
However, caution is required when measuring their survival time as it is affected
by maternal age and maternal feeding conditions. Here we provide a protocol for
powerful and reproducible measurement of the survival time in Brachionus rotifers
following a careful synchronization of culture conditions over several
generations. Empirically, poor synchronization results in early mortality and a
gradual decrease in survival rate, thus resulting in weak statistical power.
Indeed, under such conditions, calorie restriction (CR) failed to significantly
extend the lifespan of B. plicatilis although CR-induced longevity has been
demonstrated with well-synchronized rotifer samples in past and present studies.
This protocol is probably useful for other invertebrate models, including the
fruitfly Drosophila melanogaster and the nematode Caenorhabditis elegans, because
maternal age effects have also been reported in these species.
PMID- 27500470
TI - The Knife's Edge of Tolerance: Inducing Stable Multilineage Mixed Chimerism but
With a Significant Risk of CMV Reactivation and Disease in Rhesus Macaques.
AB - Although stable mixed-hematopoietic chimerism induces robust immune tolerance to
solid organ allografts in mice, the translation of this strategy to large animal
models and to patients has been challenging. We have previously shown that in MHC
matched nonhuman primates (NHPs), a busulfan plus combined belatacept and anti
CD154-based regimen could induce long-lived myeloid chimerism, but without T cell
chimerism. In that setting, donor chimerism was eventually rejected, and
tolerance to skin allografts was not achieved. Here, we describe an adaptation of
this strategy, with the addition of low-dose total body irradiation to our
conditioning regimen. This strategy has successfully induced multilineage
hematopoietic chimerism in MHC-matched transplants that was stable for as long as
24 months posttransplant, the entire length of analysis. High-level T cell
chimerism was achieved and associated with significant donor-specific
prolongation of skin graft acceptance. However, we also observed significant
infectious toxicities, prominently including cytomegalovirus (CMV) reactivation
and end-organ disease in the setting of functional defects in anti-CMV T cell
immunity. These results underscore the significant benefits that multilineage
chimerism-induction approaches may represent to transplant patients as well as
the inherent risks, and they emphasize the precision with which a clinically
successful regimen will need to be formulated and then validated in NHP models.
PMID- 27500472
TI - Loss of MiR-424-3p, not miR-424-5p, confers chemoresistance through targeting
YAP1 in non-small cell lung cancer.
AB - MiR-424 has been discovered to be involved in the chemoresistance of lung cancer.
However, the underlying mechanism by which miR-424 played role in chemoresistance
has been unknown. Here, in our study, to investigate the role of miR-424 in non
small cell lung cancer (NSCLC), we have detected the expression of miR-424-3p and
-5p in NSCLC tissues and paired normal control. Moreover, to explore the role of
miR-424-3p in NSCLC cells, miR-424-3p and -5p were both re-expressed and knocked
down using transient transfection with their respective mimics and inhibitors.
Cell viability, migration, and invasion were evaluated using MTT, wound-healing
and Transwell assays, respectively. It was found that down-regulation of miR-424
3p was pronouncedly associated with NSCLC progression and overall prognosis; and
that both miR-424-3p and -5p were markedly capable of preventing the
proliferation, migration, and invasion in NSCLC cells. Additionally, it is miR
424-3p but not miR-424-5p that enhances the chemo-sensitivity of NSCLC cells
through targeting YAP1. Mechanistically, YAP1 was identified as down-stream
target of miR-424-3p. Together, it was for the first time in our study found that
it is loss of miR-424-3p not miR-424-5p that enables chemoresistance through
targeting YAP1 in NSCLC, supporting that miR-424-3p could be used as therapeutic
target in the curing of NSCLC with chemoresistance. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27500473
TI - Instrumental Idiosyncrasies Affecting the Performance of Ultrafast Chiral and
Achiral Sub/Supercritical Fluid Chromatography.
AB - It is widely accepted that column technology is ahead of existing chromatographic
instruments. The chromatographic output may not reflect the true picture of the
peak profile inside the column. The instrumental optimization parameters become
far more important when peaks elute in a few seconds. In this work, the low
viscosity advantage of the supercritical/subcritical CO2 is coupled with the high
efficiency of narrow particle size distribution silica. Using short efficient
columns and high flow rates (up to 19 mL/min), separations on the order of a few
seconds are demonstrated. In the domain of ultrafast supercritical fluid
chromatography (SFC), unexpected results are seen which are absent in ultrafast
liquid chromatography. These effects arise due to the compressible nature of the
mobile phase and detector idiosyncrasies to eliminate back-pressure regulator
noise. We demonstrate unusual connection tubing effects with 50, 75, 127, 254,
and 500 MUm tubings and show the complex relation of dead time, retention time,
efficiency, and optimum velocity with the tubing diameter (via column outlet
pressure). Fourier analysis at different back-pressure regulator (BPR) settings
shows that some instruments have very specific noise frequencies originating from
the BPR, and those specific frequencies vanish under certain conditions. The
performance of embedded digital filters, namely, moving average, numerically
simulated low pass RC, and Gaussian kernels, is compared. This work also
demonstrates, using a simple derivative test, that some instruments employ
interpolation techniques while sampling at "true" low frequencies to avoid
picking up high frequency noise. Researchers engaged in ultrafast chromatography
need to be aware of the instrumental nuances and optimization procedures for
achieving ultrafast chiral or achiral separations in SFC mode.
PMID- 27500474
TI - [Forensic medical assessment of the cases of HIV infection and hemocontact viral
hepatitis B and C during the period from 2011 till 2015 in different subjects of
the Russian Federation].
AB - The annually increasing number of the patients presenting with HIV infection and
hemocontact viral hepatitis is naturally accompanied by the growing number of
deaths from these infectious pathologies. The objective of the present study was
to analyze the results of forensic medical expertises of the cases of HIV
infection and hemocontact viral hepatitis B and C during the period from 2011
till 2015 in different subjects of the Russian Federation. The data obtained
confirm the tendency toward the further rise in the frequency of such cases in
the practical work of forensic medical experts. Moreover, they indicate the
necessity of registration of such cases in state forensic medical expertise
organizations and open up the prospects for the development of the common
approaches to the solution of the existing problems including the evaluation of
the degree of the harm to human health.
PMID- 27500475
TI - [The classification of the injuries inflicted to the human body by gunshots from
the pneumatic weapons].
AB - The classification of the injuries inflicted to the human body by gunshots from
the pneumatic weapons remains to be developed. The objective of the present work
was to elaborate the classification of the injuries caused by gunshots from the
pneumatic weapons based on the analysis of 98 expert CONCLUSION: and acts of
forensic medical expertises (surveys) of living subjects (n=76) and corpses
(n=22) affected by gunshots from the pneumatic weapons. These materials were
collected from the bureaus of forensic medical expertise in different regions of
the Ukraine during the period from 2006 till 2015. In addition, scientific
publications concerned with the problem of interest were used along with the
relevant explanatory and terminological dictionaries. The terminology and the
conceptual framework proposed by the author in the earlier papers provided a
basis for the development of the first standard classification of the injuries
inflicted to the human body by gunshots from the pneumatic weapons categorized
into 15 groups. It is believed that this classification will lay the foundation
for the common approach of forensic medical experts to the examination and
analysis of the data on the gunshots from the pneumatic weapons used to be found
on the bodies of living subjects and the corpses. Moreover, it may be useful for
the clinicians in their diagnostic and therapeutic practices and for the legal
practitioners engaged in the quality assessment of the results of forensic
medical expertises. It is recommended to present information about the gunshots
from the pneumatic weapons in the accounting documents in a separate line.
PMID- 27500476
TI - [The peculiar features of conducting comprehensive expertises of the injuries
inflicted inside the passenger car compartment].
AB - The present article deals with the problem of forensic medical diagnostics of the
injuries inflicted inside the passenger car compartment during motor vehicle
accidents. The authors place special emphasis on the fact of a significant
increase in the number of road traffic accidents (RTA) with such consequences
throughout the world. The modern automobile industry pays much attention to the
enhancement of the car safety features by significantly improving the design of
passenger compartments. It accounts for a change in the traditional character of
the injuries to both the driver and the passengers resulting from motor vehicle
accidents. This, in turn, creates difficulties for the forensic medical experts
as regards personality identification of the subjects who happened to be inside
the car at the moment of the collision especially in the case of unascertainable
circumstances of the accident and/or the involvement of several victims. The
authors describe peculiarities of the injuries inflicted inside the passenger car
compartment during road traffic accidents including such that result from
bringing the driver and the passengers closer to the construction elements of the
car (stage I), their direct contact with these elements (stage II), and
subsequent displacement (stage III).
PMID- 27500477
TI - [The forensic-medical characteristic of the injuries inflicted to a pedestrian in
a road traffic accident by the vehicle in the side and front impact position].
AB - The objective of the present study was to distinguish between the separate phases
of the car-to-pedestrian collision with the vehicle being in the side and front
impact position. The secondary objective was to determine characteristics of
injuries specific for the collisions of this type. The methods employed in the
study included the analysis of archival materials and video sequence images. We
propose to consider a special type of injury resulting from the car-to-pedestrian
collision with the vehicle being in the side and front impact position and to
distinguish its two varieties. One of them is caused by the vehicle hitting the
pedestrian front laterally, the other arises from the oblique-transverse
collision. Each type of collision produces injuries with highly specific
characteristics.
PMID- 27500478
TI - [The reconstruction of the occurrence circumstances from the analysis of blood
stains with the use of the three-dimensional modeling technique].
AB - The present case study demonstrates the possibility of reconstruction of the
occurrence circumstances by means of the three-dimensional modeling technique and
of the application of this method for the solution of the problems facing
forensic medical expertise.
PMID- 27500479
TI - [The morphometric characteristics of the main structural components of renal
nephrons in the white rats with experimentally induced acute and chronic alcohol
intoxication].
AB - The objective of the present work was to study the morphometric characteristics
of the main structural components of renal nephrons in the white rats with the
experimentally induced acute and chronic alcohol intoxication. We undertook the
morphometric examination of the structural elements of rat kidneys with the
subsequent statistical analysis of the data obtained. The results of the study
give evidence of the toxic action of ethanol on all structural components of the
nephron in the case of both acute and chronic alcohol intoxication. The study
revealed some specific features of the development of pathological process in the
renal tissue structures at different stages of alcohol intoxication. The most
pronounced morphological changes were observed in the renal proximal tubules and
the least pronounced ones in the structure of the renal glomeruli. The earliest
morphological changes become apparent in distal convoluted tubules of the
nephron; in the case of persistent alcoholemia, they first develop in the renal
corpuscles and thereafter in the distal proximal tubules. The maximum changes
occur in the case of acute alcohol intoxication and between 2 weeks and 2 months
of chronic intoxication; they become less conspicuous during a later period.
PMID- 27500480
TI - [The peculiarities of preservation of the soft tissues and bone structures under
the conditions of prolonged corpse deposition in the high-latitude cryolitic zone
(the island Bely near the Kara Sea coast)].
AB - The objective of the present work was the primary forensic medical/medical
criminalistic study of exhumed human remains with the determination of the main
group characteristics for the purpose of evaluation of the degree of preservation
of the soft tissues and bone structures under the conditions of prolonged corpse
deposition in the high-latitude cryolitic zone. The materials available for the
study consisted of the exhumed remains of 13 corpses. The author describes the
transformed features of the soft tissues and bone structures. The former look
like a grave wax. It is shown that the peculiar morphological features of the
preserved soft tissues and bone structures depend on the burial depth and the
characteristic natural factors of the high-latitude cryolitic zone. The main
conditions influencing the state of the objects for the forensic medical
expertise are considered including prescription of corpse burying, ground
properties, freeze/thaw cycles, the influence of sea water, and microbiological
factors.
PMID- 27500481
TI - [Polymorphism of DNA nucleotide sequence as a source of enhancement of the
discrimination potential of the STR-markers].
AB - The objective of the present pilot investigation was to reveal and to study
polymorphism of nucleotide sequence in the alleles of STR loci of human autosomal
DNA with special reference to the role of this phenomenon as a source of the
differences between homonymous allelic variants. The secondary objection was to
evaluate the possibility of using the data thus obtained for the enhancement of
the informative value of the forensic medical genotyping of STR loci by means of
identification of single nucleotide polymorphisms (SNP) for the purpose of
extending their allelic spectrum. The methodological basis of the study was
constituted by the comprehensive amplified fragment length polymorphism (AFLP)
analysis and amplified fragment sequence polymorphisms (AFSP) analysis of DNA
with the use of the PLEX-ID^TM analytical mass-spectrometry platform (Abbot
Molecular, USA). The study has demonstrated that polymorphism of DNA nucleotide
sequence can be regarded as the possible source of enhancement of the
discriminating potential of STR markers. It means that the analysis of
polymorphism of DNA nucleotide sequence for genotyping AFLP-type markers of
chromosomal DNA can considerably increase the effectiveness of their application
as individualizing markers for the purpose of molecular genetic expertises.
PMID- 27500482
TI - [On the orientation of palmar whorl patterns].
AB - The objective of the present work was to study the palmar whorl patterns for the
inclusion them in the scope of dermatoglyphic signs along with the arc and loop
patterns having a well apparent structural organization. For the first time in
the history of domestic dermatoglyphic studies, we described the structure of
palmar whorl patterns (based on the palmar prints obtained from 555 subjects)
with respect to the surrounding tri-radii. Moreover, the role of their radiants
in the formation of node orientation was considered. The analysis of the variants
of palmar whorl patterns encountered in the study sample provided a basis for the
elaboration of the rule for determining their orientation. Specifically, the
orientation of the palmar whorl patterns can be found from the direction of the
embracing radiants as in the loop or complex patterns.
PMID- 27500483
TI - [The specific features of the distribution of 4-metoxyhydroxybenzene in the
organism of the warm-blooded animals suffering lethal intoxication].
AB - This work was designed to study the distribution of 4-metoxyhydroxybenzene in the
organism of the omnivorous warm-blooded animals (rats) after the intragastric
administration of this poisonous compound at a dose three-fold greater than the
LD50 value. The administered 4-metoxyhydroxybenzene was isolated from the organs
and blood of the experimental animals by exposing the biological tissues to
acetone with subsequent purification on a silica gel L 40/100 mcm using a
hexane:dioxane:propanol-2 (20:5:1) as the mobile phase. The identification and
quantitation of 4-metoxyhydroxybenzene were carried out with the use of TLC, GC
MS, and UF-spectrophotometry. It was shown that the administered 4
metoxyhydroxybenzene remained unmetabolized in the internal organs and blood of
the poisoned experimental animals. The largest amounts of 4-metoxyhydroxybenzene
were found in the stomach contents (2584,92+/-117,47), brain (59.49+/-6.05),
contents of small intestines (28.21+/-3.77), and kidneys (26.13+/-1.64).
PMID- 27500484
TI - [About the role of subjective factors in forensic expertise].
AB - The article examines the influence of subjective factors on the activities of a
forensic expert. It is noted that to improve the objectivity and reliability of
the findings of forensic experts is necessary to strictly observe the presumption
of innocence, to develop guidelines for certain types of expertise, production of
which is not carried out in the state forensic institutions, as well as carry out
some other organizational and methodical activities.
PMID- 27500485
TI - [Determination of the blood myoglobin levels for the purpose of forensic medical
expertise: the methodological peculiarities and the prospects for the further
use].
AB - The objective of the present work was to study the dependence of the blood
myoglobin levels on the time of death, gender, and age of the subject, methods
employed to analyze this protein, and the duration of storage of the biological
materials after autopsy. Myoglobin levels were measured in cadaveric blood of the
subjects who had died as a result of acute cardiovascular insufficiency and
chronic coronary heart disease in the passive hemagglutination reaction with the
use of the erythrocyte diagnosticum and in the immunoturbodimetric test combined
with the fixed time method. It was shown that the blood myoglobin level depends
on prescription of death coming, duration of storage of the biological materials,
age and sex of the deceased subject. It is concluded that the immunoturbodimetric
method is characterized by the higher accuracy and better reproducibility than
the passive hemagglutination reaction with the use of the erythrocyte
diagnosticum.
PMID- 27500486
TI - [Demonstration of the impossibility of simultaneous Dupuytren and Destot
fractures in the result of the car-pedestrian collision].
AB - This article reports the results of the commission forensic medical expertise
undertaken to evaluate the possibility of severe injury to the ankle joint
resulting from the road traffic accident as exemplified by the collision of a VAS
21043 car moving backward with a pedestrian. It was shown that the injury to the
victim's right lower leg included the tear of the right crural deltoid ligament,
the open communicated fracture of the lower third of fibular diaphysis with the
displacement of the distal fragment, the lacerated wound in the lower third of
the right leg, the rupture of distal tibiofibular synedesmosis, the closed
communicated fracture of the posterior edge of the tibia without displacement,
and outward subluxation of the right foot. According to the classification
accepted in orthopedics , this variant of the injury to the ankle joint is a
combination of the classical "complete" Dupuytren fracture and the Destot-type
fracture. The analysis of the mechanism underlying formation of such injury has
shown that it was a consequence of the indirect injurious action in the absence
of the primary impact without the car running over the victim's leg.
PMID- 27500487
TI - A randomized, controlled trial comparing skin health effects and comfort of two
adult incontinence protective underwear.
AB - BACKGROUND/PURPOSE: It is important to confirm product use effects on skin health
for products intended for prolonged skin contact. This study compared
experimental and marketed reference adult incontinence protective underwear.
METHODS: Randomized, single-blind (examiner), parallel study evaluating skin
health effects in predominantly obese incontinent women normally using protective
underwear (approximately 20% Type II Diabetes). Subjects wore experimental or
marketed reference protective underwear daily, 14 consecutive days. Visual skin
grading, transepidermal water loss (TEWL) assessed before, after 1 and 2 weeks of
product wear. Overall assessment of comfort assessed. RESULTS: Of the 122
subjects (60 experimental and 62 marketed reference), 22 were diabetic and 88
were postmenopausal. Under the conditions of this study, there were no
statistically significant differences in overall change from baseline for visual
grading and TEWL between the experimental product and the marketed reference
product for all subjects. Changes from baseline for skin erythema and skin
marking were generally small for both products for all subjects as well as for
both diabetics and non-diabetics. There were no serious adverse events (AEs), and
no withdrawals due to AEs. Overall comfort assessments of size and fit were 'just
right,' and skin comfort in the leg, waist and crotch areas were 'comfortable' or
'very comfortable' for both products. CONCLUSIONS: In-use 14-day testing
demonstrated few statistical differences between experimental product with unique
odor neutralizing technology and currently marketed product for skin assessments
and comfort. Both products were comfortable and well-tolerated.
PMID- 27500488
TI - Recurrent EZH1 mutations are a second hit in autonomous thyroid adenomas.
AB - Autonomous thyroid adenomas (ATAs) are a frequent cause of hyperthyroidism.
Mutations in the genes encoding the TSH receptor (TSHR) or the Gs protein alpha
subunit (GNAS) are found in approximately 70% of ATAs. The involvement of other
genes and the pathogenesis of the remaining cases are presently unknown. Here, we
performed whole-exome sequencing in 19 ATAs that were paired with normal DNA
samples and identified a recurrent hot-spot mutation (c.1712A>G; p.Gln571Arg) in
the enhancer of zeste homolog 1 (EZH1) gene, which codes for a catalytic subunit
of the polycomb complex. Targeted screening in an independent cohort confirmed
that this mutation occurs with high frequency (27%) in ATAs. EZH1 mutations were
strongly associated with known (TSHR, GNAS) or presumed (adenylate cyclase 9
[ADCY9]) alterations in cAMP pathway genes. Furthermore, functional studies
revealed that the p.Gln571Arg EZH1 mutation caused increased histone H3
trimethylation and increased proliferation of thyroid cells. In summary, this
study revealed that a hot-spot mutation in EZH1 is the second most frequent
genetic alteration in ATAs. The association between EZH1 and TSHR mutations
suggests a 2-hit model for the pathogenesis of these tumors, whereby constitutive
activation of the cAMP pathway and EZH1 mutations cooperate to induce the
hyperproliferation of thyroid cells.
PMID- 27500489
TI - Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity.
AB - A rise in the occurrence of obesity has driven exploration of its underlying
genetic basis and potential targets for intervention. GWAS studies have
identified obesity susceptibility pathways involving several neuropeptides that
control energy homeostasis, suggesting that variations in the genes that regulate
food intake and energy expenditure may contribute to obesity. In this study, we
identified 5 additional obesity loci, including a neuronal orphan GPCR called
Gpr45, in a forward genetic screen of mutant mice generated by piggyBac
insertional mutagenesis. Disruption of Gpr45 led to increased adiposity at the
time of weaning and increases in body mass, fat content, glucose intolerance, and
hepatic steatosis with advancing age. Mice with disruptions in Gpr45 also
displayed a reduction in expression of the metabolic regulator POMC and less
energy expenditure prior to the onset of obesity. Mechanistically, we determined
that GPR45 regulates POMC expression via the JAK/STAT pathway in a cell
autonomous manner. Consistent with this finding, intraventricular administration
of melanotan-2, an analog of the POMC derivative alpha-MSH, suppressed adult
obesity in Gpr45 mutants. These results reveal that GPR45 is a regulator of POMC
signaling and energy expenditure, which suggests that it may be a potential
intervention target to combat obesity.
PMID- 27500490
TI - ZEB1 drives epithelial-to-mesenchymal transition in lung cancer.
AB - Increased expression of zinc finger E-box binding homeobox 1 (ZEB1) is associated
with tumor grade and metastasis in lung cancer, likely due to its role as a
transcription factor in epithelial-to-mesenchymal transition (EMT). Here, we
modeled malignant transformation in human bronchial epithelial cells (HBECs) and
determined that EMT and ZEB1 expression are early, critical events in lung cancer
pathogenesis. Specific oncogenic mutations in TP53 and KRAS were required for
HBECs to engage EMT machinery in response to microenvironmental (serum/TGF-beta)
or oncogenetic (MYC) factors. Both TGF-beta- and MYC-induced EMT required ZEB1,
but engaged distinct TGF-beta-dependent and vitamin D receptor-dependent (VDR
dependent) pathways, respectively. Functionally, we found that ZEB1 causally
promotes malignant progression of HBECs and tumorigenicity, invasion, and
metastases in non-small cell lung cancer (NSCLC) lines. Mechanistically, ZEB1
expression in HBECs directly repressed epithelial splicing regulatory protein 1
(ESRP1), leading to increased expression of a mesenchymal splice variant of CD44
and a more invasive phenotype. In addition, ZEB1 expression in early stage IB
primary NSCLC correlated with tumor-node-metastasis stage. These findings
indicate that ZEB1-induced EMT and associated molecular changes in ESRP1 and CD44
contribute to early pathogenesis and metastatic potential in established lung
cancer. Moreover, TGF-beta and VDR signaling and CD44 splicing pathways
associated with ZEB1 are potential EMT chemoprevention and therapeutic targets in
NSCLC.
PMID- 27500491
TI - MondoA coordinately regulates skeletal myocyte lipid homeostasis and insulin
signaling.
AB - Intramuscular lipid accumulation is a common manifestation of chronic caloric
excess and obesity that is strongly associated with insulin resistance. The
mechanistic links between lipid accumulation in myocytes and insulin resistance
are not completely understood. In this work, we used a high-throughput chemical
biology screen to identify a small-molecule probe, SBI-477, that coordinately
inhibited triacylglyceride (TAG) synthesis and enhanced basal glucose uptake in
human skeletal myocytes. We then determined that SBI-477 stimulated insulin
signaling by deactivating the transcription factor MondoA, leading to reduced
expression of the insulin pathway suppressors thioredoxin-interacting protein
(TXNIP) and arrestin domain-containing 4 (ARRDC4). Depleting MondoA in myocytes
reproduced the effects of SBI-477 on glucose uptake and myocyte lipid
accumulation. Furthermore, an analog of SBI-477 suppressed TXNIP expression,
reduced muscle and liver TAG levels, enhanced insulin signaling, and improved
glucose tolerance in mice fed a high-fat diet. These results identify a key role
for MondoA-directed programs in the coordinated control of myocyte lipid balance
and insulin signaling and suggest that this pathway may have potential as a
therapeutic target for insulin resistance and lipotoxicity.
PMID- 27500492
TI - Biallelic inactivation of REV7 is associated with Fanconi anemia.
AB - Fanconi anemia (FA) is a recessive genetic disease characterized by congenital
abnormalities, chromosome instability, progressive bone marrow failure (BMF), and
a strong predisposition to cancer. Twenty FA genes have been identified, and the
FANC proteins they encode cooperate in a common pathway that regulates DNA
crosslink repair and replication fork stability. We identified a child with
severe BMF who harbored biallelic inactivating mutations of the translesion DNA
synthesis (TLS) gene REV7 (also known as MAD2L2), which encodes the mutant REV7
protein REV7-V85E. Patient-derived cells demonstrated an extended FA phenotype,
which included increased chromosome breaks and G2/M accumulation upon exposure to
DNA crosslinking agents, gammaH2AX and 53BP1 foci accumulation, and enhanced
p53/p21 activation relative to cells derived from healthy patients. Expression of
WT REV7 restored normal cellular and functional phenotypes in the patient's
cells, and CRISPR/Cas9 inactivation of REV7 in a non-FA human cell line produced
an FA phenotype. Finally, silencing Rev7 in primary hematopoietic cells impaired
progenitor function, suggesting that the DNA repair defect underlies the
development of BMF in FA. Taken together, our genetic and functional analyses
identified REV7 as a previously undescribed FA gene, which we term FANCV.
PMID- 27500493
TI - Mitochondrial calcium uptake underlies ROS generation during aminoglycoside
induced hair cell death.
AB - Exposure to aminoglycoside antibiotics can lead to the generation of toxic levels
of reactive oxygen species (ROS) within mechanosensory hair cells of the inner
ear that have been implicated in hearing and balance disorders. Better
understanding of the origin of aminoglycoside-induced ROS could focus the
development of therapies aimed at preventing this event. In this work, we used
the zebrafish lateral line system to monitor the dynamic behavior of
mitochondrial and cytoplasmic oxidation occurring within the same dying hair cell
following exposure to aminoglycosides. The increased oxidation observed in both
mitochondria and cytoplasm of dying hair cells was highly correlated with
mitochondrial calcium uptake. Application of the mitochondrial uniporter
inhibitor Ru360 reduced mitochondrial and cytoplasmic oxidation, suggesting that
mitochondrial calcium drives ROS generation during aminoglycoside-induced hair
cell death. Furthermore, targeting mitochondria with free radical scavengers
conferred superior protection against aminoglycoside exposure compared with
identical, untargeted scavengers. Our findings suggest that targeted therapies
aimed at preventing mitochondrial oxidation have therapeutic potential to
ameliorate the toxic effects of aminoglycoside exposure.
PMID- 27500494
TI - Oxygen metabolism and barrier regulation in the intestinal mucosa.
AB - Mucosal surfaces are lined by epithelial cells and provide an important barrier
to the flux of antigens from the outside. This barrier is provided at a number of
levels, including epithelial junctional complexes, mucus production, and mucosa
derived antimicrobials. Tissue metabolism is central to the maintenance of
homeostasis in the mucosa. In the intestine, for example, baseline pO2 levels are
uniquely low due to counter-current blood flow and the presence of large numbers
of bacteria. As such, hypoxia and HIF signaling predominates normal intestinal
metabolism and barrier regulation during both homeostasis and active
inflammation. Contributing factors that elicit important adaptive responses
within the mucosa include the transcriptional regulation of tight junction
proteins, metabolic regulation of barrier components, and changes in autophagic
flux. Here, we review recent literature around the topic of hypoxia and barrier
function in health and during disease.
PMID- 27500497
TI - Homing is not for everyone: displaced cardinalfish find a new place to live.
AB - It was tested whether the pajama cardinalfish Sphaeramia nematoptera (Apogonidae)
could home by displacing individuals up to 250 m within and among isolated reefs.
Contrary to expectations, only two of 37 (5.4%) displaced S. nematoptera returned
home and another 16 (43.2%) were found to have joined other social groups and did
not home after 26 months of observations; while over the same period, 94% of
control S. nematoptera remained associated with home corals, demonstrating strong
site attachment. Hence, while this species has the potential to return home,
being able to do so may not be as critical as previously assumed.
PMID- 27500495
TI - BRPF1 is essential for development of fetal hematopoietic stem cells.
AB - Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell
types and are clinically useful for a variety of HSC transplantation-based
therapies. Understanding the role of chromatin organization and regulation in HSC
homeostasis may provide important insights into HSC development. Bromodomain- and
PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that
possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases
(KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to
stimulate crosstalk between different chromatin modifications. Here, we
investigated the function of BRPF1 in hematopoiesis by selectively deleting its
gene in murine blood cells. Brpf1-deficient pups experienced early lethality due
to acute bone marrow failure and aplastic anemia. The mutant bone marrow and
fetal liver exhibited severe deficiency in HSCs and hematopoietic progenitors,
along with elevated reactive oxygen species, senescence, and apoptosis. BRPF1
deficiency also reduced the expression of multipotency genes, including Slamf1,
Mecom, Hoxa9, Hlf, Gfi1, Egr, and Gata3. Furthermore, BRPF1 was required for
acetylation of histone H3 at lysine 23, a highly abundant but not well
characterized epigenetic mark. These results identify an essential role of the
multivalent chromatin regulator BRPF1 in definitive hematopoiesis and illuminate
a potentially new avenue for studying epigenetic networks that govern HSC
ontogeny.
PMID- 27500496
TI - A colitogenic memory CD4+ T cell population mediates gastrointestinal graft
versus-host disease.
AB - Damage to the gastrointestinal tract is a major cause of morbidity and mortality
in graft-versus-host disease (GVHD) and is attributable to T cell-mediated
inflammation. In this work, we identified a unique CD4+ T cell population that
constitutively expresses the beta2 integrin CD11c and displays a biased central
memory phenotype and memory T cell transcriptional profile, innate-like
properties, and increased expression of the gut-homing molecules alpha4beta7 and
CCR9. Using several complementary murine GVHD models, we determined that adoptive
transfer and early accumulation of beta2 integrin-expressing CD4+ T cells in the
gastrointestinal tract initiated Th1-mediated proinflammatory cytokine
production, augmented pathological damage in the colon, and increased mortality.
The pathogenic effect of this CD4+ T cell population critically depended on
coexpression of the IL-23 receptor, which was required for maximal inflammatory
effects. Non-Foxp3-expressing CD4+ T cells produced IL-10, which regulated
colonic inflammation and attenuated lethality in the absence of functional
CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23
receptor defines an IL-10-regulated, colitogenic memory CD4+ T cell subset that
is poised to initiate inflammation when there is loss of tolerance and breakdown
of mucosal barriers.
PMID- 27500498
TI - Regulation of the vitamin D receptor by vitamin D lactam derivatives.
AB - The active metabolite of vitamin D3 , 1alpha,25-dihydroxyvitamin D3 , acts as a
ligand for the vitamin D receptor (VDR) and activates VDR-mediated gene
expression. Recently, we characterized 1alpha,25-dihydroxyvitamin D3 -26,23
lactams (DLAMs), which mimic vitamin D3 metabolites, as noncalcemic VDR ligands
that barely activate the receptor. In this study, we present structural insights
onto the regulation of VDR function by DLAMs. X-ray crystallographic analysis
revealed that DLAMs induced a large conformational change in the loop region
between helices H6 and H7 in the VDR ligand-binding domain. Our structural
analysis suggests that targeting of the loop region may be a new mode of VDR
regulation.
PMID- 27500499
TI - Technology-assisted self-testing and management of oral anticoagulation therapy:
a qualitative patient-focused study.
AB - BACKGROUND: Oral anticoagulation therapy requires regular blood testing to ensure
therapeutic levels are maintained and excessive bleeding/clotting is avoided.
Technology-assisted self-testing and management is seen as one of the key areas
in which quality of care can be improved whilst reducing costs. Nevertheless,
levels of patient engagement in self-testing and management remain low. To date,
little research emphasis has been placed on understanding the patients'
perspectives for low engagement. The typical approach adopted by healthcare
providers is to provide patient education programmes, with the expectation that
individual patients will change their behaviour and adopt new self-care
strategies. However, if levels of patient engagement are to be increased,
healthcare providers must also develop a better understanding of how their
clinical service provision is perceived by patients and make adaptations.
OBJECTIVE: To explore patient views, needs and expectations of an anticoagulation
service and the self-testing and management services provided. METHODS:
Interviews were conducted with 17 patients who currently engage in international
normalised ratio (INR) self-testing and management. Thematic coding and analysis
were carried out on the interview transcripts. RESULTS: Four high-level themes
emerged from interviews: (i) role of clinic, (ii) motivations for self-testing,
(iii) managing INR and (iv) trust. The clinic was seen as adding value in terms
of specifying testing frequency, dosage profiles and calibrating equipment.
Prompt communication from clinic to patient was also valued, although more
personalised/real-time communication would help avoid feelings of isolation.
Patients felt more in control as self-tester/managers and often took decisions
about treatment adjustments themselves. However, some also manipulated their own
test results to avoid 'unnecessary' interventions. CONCLUSIONS AND
RECOMMENDATIONS: More personalised/real-time communication, pragmatic and
collaborative patient-clinician partnerships and recognition of expert patient
knowledge and expertise are needed if increased levels of engagement with self
testing and management service provision is to be realised.
PMID- 27500500
TI - Poly(polyol sebacate) Elastomers as Coatings for Metallic Coronary Stents.
AB - Biocompatible polymeric coatings for metallic stents are desired, as currently
used materials present limitations such as deformation during degradation and
exponential loss of mechanical properties after implantation. These concerns,
together with the present risks of the drug-eluting stents, namely, thrombosis
and restenosis, require new materials to be studied. For this purpose, novel
poly(polyol sebacate)-derived polymers are investigated as coatings for metallic
stents. All pre-polymers reveal a low molecular weight between 3000 and 18 000 g
mol-1 . The cured polymers range from flexible to more rigid, with E-modulus
between 0.6 and 3.8 MPa. Their advantages include straightforward synthesis,
biodegradability, easy processing through different scaffolding techniques, and
easy transfer to industrial production. Furthermore, electrospraying and dip
coating procedures are used as proof-of-concept to create coatings on metallic
stents. Biocompatibility tests using adipose stem cells lead to promising results
for the use of these materials as coatings for metallic coronary stents.
PMID- 27500501
TI - Impact of Maternal Body Mass Index on Intrapartum and Neonatal Outcomes in
Brisbane, Australia, 2007 to 2013.
AB - BACKGROUND: The aim of this study was to evaluate the influence of maternal body
mass index on intrapartum and neonatal outcomes at one of the largest maternity
hospitals in Australia. METHODS: A retrospective cross-sectional study of 55,352
term singleton deliveries at the Mater Mothers' Hospital in Brisbane, Australia,
was conducted. The study cohort was stratified into six groups based on the World
Health Organization's body mass index classification. The normal body mass index
category was the reference group for all comparisons. Multivariate logistic
regression was used to examine the effect of maternal body mass index, adjusted
for maternal age, ethnicity, parity, and preexisting conditions (e.g., diabetes
mellitus and hypertension), on selected intrapartum and neonatal outcomes.
RESULTS: Women in the overweight and Obese I, II, and III categories were more
likely to have chronic or gestational hypertension/preeclampsia, and preexisting
or gestational diabetes mellitus. They also had an increased risk for induction
of labor, elective and emergency cesarean, and postpartum hemorrhage. Underweight
women were less likely to require induction of labor and emergency cesarean.
Infants born to women with increased body mass index were more likely to require
neonatal resuscitation, neonatal intensive care unit admission, and have lower
Apgar scores at 5 minutes. CONCLUSION: There is an increased risk of adverse
intrapartum and neonatal outcomes for women who are overweight and obese, with
the risks increasing with rising body mass index. Appropriately targeted weight
management strategies and health education may yield improved maternal and
perinatal outcomes if effectively implemented before pregnancy. These may
particularly be of benefit in the teenage cohort that has yet to embark on
pregnancy.
PMID- 27500502
TI - Deadwood stocks increase with selective logging and large tree frequency in
Gabon.
AB - Deadwood is a major component of aboveground biomass (AGB) in tropical forests
and is important as habitat and for nutrient cycling and carbon storage. With
deforestation and degradation taking place throughout the tropics, improved
understanding of the magnitude and spatial variation in deadwood is vital for the
development of regional and global carbon budgets. However, this potentially
important carbon pool is poorly quantified in Afrotropical forests and the
regional drivers of deadwood stocks are unknown. In the first large-scale study
of deadwood in Central Africa, we quantified stocks in 47 forest sites across
Gabon and evaluated the effects of disturbance (logging), forest structure
variables (live AGB, wood density, abundance of large trees), and abiotic
variables (temperature, precipitation, seasonality). Average deadwood stocks
(measured as necromass, the biomass of deadwood) were 65 Mg ha-1 or 23% of live
AGB. Deadwood stocks varied spatially with disturbance and forest structure, but
not abiotic variables. Deadwood stocks increased significantly with logging (+38
Mg ha-1 ) and the abundance of large trees (+2.4 Mg ha-1 for every tree >60 cm
dbh). Gabon holds 0.74 Pg C, or 21% of total aboveground carbon in deadwood, a
threefold increase over previous estimates. Importantly, deadwood densities in
Gabon are comparable to those in the Neotropics and respond similarly to logging,
but represent a lower proportion of live AGB (median of 18% in Gabon compared to
26% in the Neotropics). In forest carbon accounting, necromass is often assumed
to be a constant proportion (9%) of biomass, but in humid tropical forests this
ratio varies from 2% in undisturbed forest to 300% in logged forest. Because
logging significantly increases the deadwood carbon pool, estimates of tropical
forest carbon should at a minimum use different ratios for logged (mean of 30%)
and unlogged forests (mean of 18%).
PMID- 27500503
TI - Mechanistic Insights and Computational Design of Transition-Metal Catalysts for
Hydrogenation and Dehydrogenation Reactions.
AB - Catalytic hydrogenation and dehydrogenation reactions are fundamentally important
in chemical synthesis and industrial processes, as well as potential applications
in the storage and conversion of renewable energy. Modern computational quantum
chemistry has already become a powerful tool in understanding the structures and
properties of compounds and elucidating mechanistic insights of chemical
reactions, and therefore, holds great promise in the design of new catalysts.
Herein, we review our computational studies on the catalytic hydrogenation of
carbon dioxide and small organic carbonyl compounds, and on the dehydrogenation
of amine-borane and alcohols with an emphasis on elucidating reaction mechanisms
and predicting new catalytic reactions, and in return provide some general ideas
for the design of high-efficiency, low-cost transition-metal complexes for
hydrogenation and dehydrogenation reactions.
PMID- 27500504
TI - Synthesis of Silver(I) and Gold(I) Complexes Containing Enantiopure Pybox
Ligands. First Assays on the Silver(I)-Catalyzed Asymmetric Addition of Alkynes
to Imines.
AB - Dinuclear complexes [Ag2(CF3SO3){(S,S)-(i)Pr-pybox}2][CF3SO3] (1), [Ag2(R
pybox)2][X]2 [R-pybox = 2,6-bis[4-(S)-isopropyloxazolin-2-yl]pyridine (S,S)-(i)Pr
pybox and X = PF6 (2) and BF4 (3); R-pybox = 2,6-bis[(3aS,8aR)-8,8a-dihydro-3aH
indeno[1,2-d]oxazol-2-yl]pyridine (3aS,3a'S,8aR,8a'R)-indane-pybox and X = CF3SO3
(4)], [Ag2{(S,S)-(i)Pr-pybox}{(3aS,3a'S,8aR,8a'R)-indane-pybox}][CF3SO3]2 (5),
and [Ag2(R-pybox)3][X]2 [R-pybox = (3aS,3a'S,8aR,8a'R)-indane-pybox and X =
CF3SO3 (10), SF6 (11), and PF6 (12)] as well as mononuclear complexes [Ag(R
pybox)2][X] [R-pybox = (S,S)-(i)Pr-pybox and X = SbF6 (6), PF6 (7), and BF4 (8);
R-pybox = (3aS,3a'S,8aR,8a'R)-indane-pybox) and X = BF4 (9)] have been prepared
by the reaction of the corresponding silver salts and pybox ligands using the
appropriate molar ratio conditions. The first gold(I)/pybox complex [Au6Cl4{(S,S)
(i)Pr-pybox}4][AuCl2]2 (13) has been synthesized by the reaction of
[AuCl{S(CH3)2}] and (S,S)-(i)Pr-pybox (1:1 molar ratio) in acetonitrile. The
structures of the dinuclear (1, 4, 5, 10, and 11) and mononuclear (6 and 9)
silver complexes and the hexanuclear gold complex 13 have been determined by
single-crystal X-ray diffraction analysis. These studies have been complemented
with a solution-state study by NMR spectroscopy, which included structure
elucidation, variable-temperature measurements, and diffusion studies using
diffusion-ordered spectroscopy (DOSY; for complexes 1, 4, 10, and 12). Complexes
1, 2, 4, and 10 have been assayed as catalysts in the asymmetric addition of
phenylacetylene to N-benzylideneaniline.
PMID- 27500507
TI - Parents with mental illness - a qualitative study of identities and experiences
with support services.
AB - : WHAT IS KNOWN ON THE SUBJECT?: According to estimates more than half of adult
mental health service users are parents, but their experiences are largely
lacking from research literature. Parental mental illness can often be viewed
from a risk perspective. Parents with mental illness and their families have
unmet support needs. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Parents with
mental illness want acknowledgement that they can be able and responsible. Many
parents adopt an expert by experience identity. Fathers can feel their parental
role is not recognized and mothers express fears of being judged if they discuss
their illness. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Adult mental health
services need to recognize and support parental role of service users. Joint care
planning and family oriented care should be promoted. Professionals should take
advantage of the knowledge of these parents and they could be more actively
engaged in service development. ABSTRACT: Introduction Parental mental illness is
often viewed from a risk perspective. Despite this, being a parent can be both
valuable and motivating. Research literature lacks the perspective of mothers and
fathers, who have experienced mental illness. Aim This study explores how parents
with mental illness construct their identities as mothers and fathers and their
experiences with health and social care services. Method Three focus groups with
19 participants were conducted in Finland and Scotland. Methods of discourse
analysis have been used in to analyse the interview data. Results Adult service
users want their parenting role recognized and supported. Parents have knowledge
and skills which can be utilized and many have adopted an expert by experience
identity. Discussion Being able to see oneself as a 'good' parent can be
challenging but important. Parents may require support, but want to be included
in the planning of their care. Services could make more use of the knowledge and
skills parents and families have, and joint working could lessen parents'
anxieties. Implications for practice Mental health practitioners are in a key
position in providing more family centred, resource focused care. Service user
expertise should be acknowledged in clinical practice.
PMID- 27500505
TI - Rise and fall of vector infectivity during sequential strain displacements by
mosquito-borne dengue virus.
AB - Each of the four serotypes of mosquito-borne dengue virus (DENV-1-4) comprises
multiple, genetically distinct strains. Competitive displacement between strains
within a serotype is a common feature of DENV epidemiology and can trigger
outbreaks of dengue disease. We investigated the mechanisms underlying two
sequential displacements by DENV-3 strains in Sri Lanka that each coincided with
abrupt increases in dengue haemorrhagic fever (DHF) incidence. First, the post
DHF strain displaced the pre-DHF strain in the 1980s. We have previously shown
that post-DHF is more infectious than pre-DHF for the major DENV vector, Aedes
aegypti. Then, the ultra-DHF strain evolved in situ from post-DHF and displaced
its ancestor in the 2000s. We predicted that ultra-DHF would be more infectious
for Ae. aegypti than post-DHF but found that ultra-DHF infected a significantly
lower percentage of mosquitoes than post-DHF. We therefore hypothesized that
ultra-DHF had effected displacement by disseminating in Ae. aegypti more rapidly
than post-DHF, but this was not borne out by a time course of mosquito infection.
To elucidate the mechanisms that shape these virus-vector interactions, we tested
the impact of RNA interference (RNAi), the principal mosquito defence against
DENV, on replication of each of the three DENV strains. Replication of all
strains was similar in mosquito cells with dysfunctional RNAi, but in cells with
functional RNAi, replication of pre-DHF was significantly suppressed relative to
the other two strains. Thus, differences in susceptibility to RNAi may account
for the differences in mosquito infectivity between pre-DHF and post-DHF, but
other mechanisms underlie the difference between post-DHF and ultra-DHF.
PMID- 27500506
TI - Chemical composition and antimicrobial activity of Micromeria hedgei Rech. f. oil
from Iran.
AB - Micromeria hedgei belongs to the Lamiaceae family and is a rare endemic and
endangered species that has been used in traditional medicine in Iran. In this
regard, essential oil composition and antimicrobial activity of wild and
cultivated M. hedgei was reported for the first time. Essential oils isolated via
hydro distillation from the aerial parts of M. hedgei were analysed by a
combination of capillary GC and GC-MS. The major constituents were geranial
(18.04 and 22.68%), neral (13.81 and 15.99%), geraniol (13.15 and 10.74%), nerol
(7.69 and 6.02%), E-caryophyllene (6.52-3.80%), carvacrol (6.20 and 5.27%),
geranyl acetate (5.79 and 3.06%), caryophyllene oxide (4.73 and 3.88%), thymol
(3.13 and 3.63%) and alpha-humulene (3.27 and 3.27%) in wild and cultivated M.
hedgei. Antimicrobial activity of essential oils was investigated by disc
diffusion method. Essential oil showed good antimicrobial activity against five
medically important pathogens compared with standard antibiotics.
PMID- 27500508
TI - A novel case presenting with an unusual ureteral diverticular lesion similar to
adenomyomatous hyperplasia of the gallbladder.
AB - We present the first case of an unusual ureteral diverticular lesion
demonstrating similarities to adenomyomatous hyperplasia of the gallbladder. A 68
year-old asymptomatic Japanese man with high prostate-specific antigen levels was
clinically evaluated. Left hydronephrosis and benign prostatic hyperplasia were
detected. A bilateral retrograde pyelogram revealed that the upper and middle
portions of the left ureter exhibited an irregular narrow lumen and some pooling
of contrast material, which was compatible with ureteral pseudodiverticulosis.
Although no malignant cells were seen on cytology, computed tomography detected a
fusiform shaped lesion with a circumferential thick wall including multiple
diverticulae. Left nephroureterectomy was performed because malignancy could not
be ruled out. Pathology demonstrated that the ureteral lesion showed a localized
thick wall consisting of multilocules and/or multicysts and a hyperplastic
muscularis propria. The cysts were mostly seen in the muscularis propria or a
deeper site. The inner layers of the cysts were lined with normal urothelium, and
some cysts opened onto the mucosal surface, indicating that they were derived
from invaginated mucosal epithelium. We believe that this lesion may be a novel
form of diverticular disorder demonstrating similarities to adenomyomatous
hyperplasia of the gallbladder.
PMID- 27500509
TI - Pituitary Non-Functioning Adenoma Disclosed at 18F-Choline PET/CT to Investigate
a Prostate Cancer Relapse.
AB - We report the incidental finding of a pituitary macroadenoma on an F-choline
PET/CT in a patient with recurrent prostate cancer. The pituitary gland was
clearly enlarged and intensely FDG avid (SUVmax, 6.6). The diagnosis was
confirmed by a subsequent contrast-enhanced MR evaluation, and the macroadenoma
was classified as nonfunctioning on the basis of normality of the specific serum
hormonal profile. A follow-up F-choline PET/CT scan performed after 6 months
revealed stable dimension, and uptake of the pituitary macroadenoma patient
deceased 1 month later. At autopsy, intracytoplasmic vesicles containing growth
and prolactin hormones were observed at immunohistochemistry.
PMID- 27500510
TI - Differences in Uptake of 18F-FDG and 11C-Choline in a Case of Acute Myeloid
Leukemia.
AB - A 26-year-old man had unilateral facial numbness. A brain MRI suggested possible
brain metastases. F-FDG and C-choline PET/CT revealed multiple sites of abnormal
activity in the body. However, C-choline PET/CT was more impressive than FDG
PET/CT. Especially, the brain lesions revealed by MRI had only elevated C-choline
uptake but had FDG uptake levels similar to adjacent brain. Acute myeloid
leukemia was diagnosed after bone marrow biopsy.
PMID- 27500511
TI - 68Ga DOTATATE PET/CT in Differentiated Thyroid Carcinoma With Fibular Metastasis
and Mixed Response to Sorafenib.
AB - We describe somatostatin receptor targeted imaging findings in a 56-year-old
woman with elevated serum thyroglobulin and radioiodine negative DTC fibular
metastasis. The fibular lesion was biopsy proven of poorly differentiated thyroid
carcinoma and demonstrated high grade uptake on Tc-HYNIC-TOC scintigraphy. She
opted for sorafenib therapy for progressively increasing fibular swelling and was
started on 400 mg daily followed by dose escalation to 400 mg twice daily. At 17
months after sorafenib initiation, Ga DOTATATE PET/CT demonstrated necrosis of
the fibular lesion; however, new lesions were documented in lower dorsal and
lumbar vertebrae and skull, based upon which sorafenib withdrawal was
contemplated.
PMID- 27500513
TI - The Synthesis of Multisubstituted Pyrroles via a Copper-Catalyzed Tandem Three
Component Reaction.
AB - An unprecedented nucleophilic addition/cyclization/aromatization cascade of basic
chemicals, i.e., aromatic alkenes/alkynes, trimethylsilyl cyanide and N,N
disubstituted formamide, has been developed to give a series of multisubstituted
pyrroles in moderate to good yields with high regioselectivities. This reaction
not only reveals a new reaction mode for alpha-aminonitriles, but also provides a
new and efficient cyclization pattern for the synthesis of multisubstituted
pyrroles as well as their derivatives, which might facilitate related biological
studies.
PMID- 27500512
TI - Disease-specific scoring or generic scoring in ICU?
PMID- 27500514
TI - Ronald W. Waynant, PhD (October 4, 1940-May 8, 2016).
PMID- 27500515
TI - Self-Aggregating Deep Cavitand Acts as a Fluorescence Displacement Sensor for
Lysine Methylation.
AB - A dual-mode aggregative host:guest indicator displacement sensing system has been
created for the detection of trimethylated peptides and determination of histone
demethylase activity. The combination of selective recognition of suitably sized
trimethylammonium salts and reversible lipophilic aggregation of the host:guest
complex provides a unique quenching mechanism that is not only dependent on
affinity for sensitivity but the lipophilicity of the indicator. In addition,
aggregation can be controlled by the application of chaotropic anions in the
mixture, allowing a second level of discrimination between hard lysine groups and
softer trimethyllysines.
PMID- 27500516
TI - Autoradiographic Measurements of [14C]-Iodoantipyrine in Rat Brain Following
Central Post-Stroke Pain.
AB - Approximately 8% of stroke patients present symptoms of central post-stroke pain
(CPSP). CPSP is associated with allodynia and hypersensitivity to nociceptive
stimuli. Although some studies have shown that neuropathic pain may involve the
dorsolateral prefrontal cortex, rostral anterior cingulate cortex, amygdala,
hippocampus, periaqueductal gray, rostral ventromedial medulla, and medial
thalamus, the neural substrates and their connections that mediate CPSP remain
unclear. [(14)C]-Iodoantipyrine (IAP) uptake can be measured to evaluate
spontaneously active pain. It can be used to assess the activation of neural
substrates that may be involved in CPSP in an animal model. The [(14)C]-IAP
method in rats is less expensive to perform compared with other brain mapping
techniques. The present [(14)C]-IAP protocol is used to measure the activation of
neural substrates that are involved in CPSP that is induced by lesions of the
ventral basal nucleus (VB) of the thalamus in a rodent model.
PMID- 27500517
TI - Response to "Concerning the Article Entitled 'Judgment of Nasolabial Esthetics in
Cleft Lip and Palate Is Not Influenced by Overall Facial Attractiveness'".
PMID- 27500518
TI - Cleidocranial Dysplasia with 6p21.1-p12.3 Microdeletion: A Case Report and
Literature Review.
AB - OBJECTIVE: The aim of this article is to publish a literature review and report
on a new case of cleidocranial dysplasia syndrome with 6p21.1-p12.3
microdeletion. DESIGN: A PubMed search using "cleidocranial dysplasia syndrome
(CCD)" or "6p microdeletion" was performed. Articles with information relevant to
our case were obtained for review. A new case of cleidocranial dysplasia syndrome
is presented to describe and discuss clinical manifestations, pathogenesis,
clinical progression of cleidocranial dysplasia syndrome, and management.
RESULTS: There were 22 articles with reports of cleidocranial dysplasia syndrome
or 6p microdeletion. Cleidocranial dysplasia syndrome, a rare genetic disorder,
documented to have an autosomal dominant inheritance pattern and caused by caused
by mutations of the transcription factor RUNX2. RUNX2 has been mapped to
chromosome 6p21. The anomalies in cleidocranial dysplasia syndrome can involve
not only the clavicle and skull but the entire skeleton because the membranous as
well as endochondral bone formation may be affected. Upon follow-up, our patient
was found to have global developmental delay. CONCLUSIONS: We report a near-term
neonate with characteristic features of cleidocranial dysplasia and a 6p21.1
p12.3 microdeletion. Cleidocranial dysplasia syndrome is a rare autosomal
dominant skeletal dysplasia. The mutation of the RUNX2 gene results in
cleidocranial dysplasia syndrome.
PMID- 27500519
TI - Cardiopulmonary dysfunction in patients with limb-girdle muscular dystrophy 2A.
AB - INTRODUCTION: Little is known about the frequency of cardiopulmonary failure in
limb-girdle muscular dystrophy type 2A (calpainopathy) patients, although some
studies have reported severe cardiomyopathy or respiratory failure. METHODS: To
clarify the frequency of cardiopulmonary dysfunction in this patient population,
we retrospectively reviewed the respiratory and cardiac function of 43 patients
with calpainopathy. RESULTS: Nine of the 43 patients had forced vital capacity
(FVC) < 80%, and 3 used noninvasive positive pressure ventilation. Mean FVC was
significantly lower in patients who were nonambulant and had normal creatine
kinase levels. Only 1 patient had a prolonged QRS complex duration.
Echocardiography revealed that 1 patient had very mild left ventricular
dysfunction. CONCLUSIONS: These findings suggest that patients with calpainopathy
may develop severe respiratory failure, but cardiac dysfunction is infrequent.
Muscle Nerve 55: 465-469, 2017.
PMID- 27500520
TI - The Eucalyptus linker histone variant EgH1.3 cooperates with the transcription
factor EgMYB1 to control lignin biosynthesis during wood formation.
AB - Wood, also called secondary xylem, is a specialized vascular tissue constituted
by different cell types that undergo a differentiation process involving
deposition of thick, lignified secondary cell walls. The mechanisms needed to
control the extent of lignin deposition depending on the cell type and the
differentiation stage are far from being fully understood. We found that the
Eucalyptus transcription factor EgMYB1, which is known to repress lignin
biosynthesis, interacts specifically with a linker histone variant, EgH1.3. This
interaction enhances the repression of EgMYB1's target genes, strongly limiting
the amount of lignin deposited in xylem cell walls. The expression profiles of
EgMYB1 and EgH1.3 overlap in xylem cells at early stages of their differentiation
as well as in mature parenchymatous xylem cells, which have no or only thin
lignified secondary cell walls. This suggests that a complex between EgMYB1 and
EgH1.3 integrates developmental signals to prevent premature or inappropriate
lignification of secondary cell walls, providing a mechanism to fine-tune the
differentiation of xylem cells in time and space. We also demonstrate a role for
a linker histone variant in the regulation of a specific developmental process
through interaction with a transcription factor, illustrating that plant linker
histones have other functions beyond chromatin organization.
PMID- 27500521
TI - Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular
Matrix.
AB - The architecture of branched organs such as the lungs, kidneys, and mammary
glands arises through the developmental process of branching morphogenesis, which
is regulated by a variety of soluble and physical signals in the
microenvironment. Described here is a method created to study the process of
branching morphogenesis by forming engineered three-dimensional (3D) epithelial
tissues of defined shape and size that are completely embedded within an
extracellular matrix (ECM). This method enables the formation of arrays of
identical tissues and enables the control of a variety of environmental factors,
including tissue geometry, spacing, and ECM composition. This method can also be
combined with widely used techniques such as traction force microscopy (TFM) to
gain more information about the interactions between cells and their surrounding
ECM. The protocol can be used to investigate a variety of cell and tissue
processes beyond branching morphogenesis, including cancer invasion.
PMID- 27500522
TI - Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of
Melatonin Against Hypoxia/reoxygenation-induced Disruption.
AB - This protocol describes how villous cytotrophoblast cells are isolated from
placentas at term by successive enzymatic digestions, followed by density
centrifugation, media gradient isolation and immunomagnetic purification. As
observed in vivo, mononucleated villous cytotrophoblast cells in primary culture
differentiate into multinucleated syncytiotrophoblast cells after 72 hr. Compared
to normoxia (8% O2), villous cytotrophoblast cells that undergo
hypoxia/reoxygenation (0.5% / 8% O2) undergo increased oxidative stress and
intrinsic apoptosis, similar to that observed in vivo in pregnancy complications
such as preeclampsia, preterm birth, and intrauterine growth restriction. In this
context, primary villous trophoblasts cultured under hypoxia/reoxygenation
conditions represent a unique experimental system to better understand the
mechanisms and signalling pathways that are altered in human placenta and
facilitate the search for effective drugs that protect against certain pregnancy
disorders. Human villous trophoblasts produce melatonin and express its
synthesizing enzymes and receptors. Melatonin has been suggested as a treatment
for preeclampsia and intrauterine growth restriction because of its protective
antioxidant effects. In the primary villous cytotrophoblast cell model described
in this paper, melatonin has no effect on trophoblast cells in normoxic state but
restores the redox balance of syncytiotrophoblast cells disrupted by
hypoxia/reoxygenation. Thus, human villous trophoblast cells in primary culture
are an excellent approach to study the mechanisms behind the protective effects
of melatonin on placental function during hypoxia/reoxygenation.
PMID- 27500524
TI - Domestication history and geographical adaptation inferred from a SNP map of
African rice.
AB - African rice (Oryza glaberrima Steud.) is a cereal crop species closely related
to Asian rice (Oryza sativa L.) but was independently domesticated in West Africa
~3,000 years ago. African rice is rarely grown outside sub-Saharan Africa but is
of global interest because of its tolerance to abiotic stresses. Here we describe
a map of 2.32 million SNPs of African rice from whole-genome resequencing of 93
landraces. Population genomic analysis shows a population bottleneck in this
species that began ~13,000-15,000 years ago with effective population size
reaching its minimum value ~3,500 years ago, suggesting a protracted period of
population size reduction likely commencing with predomestication management
and/or cultivation. Genome-wide association studies (GWAS) for six salt tolerance
traits identify 11 significant loci, 4 of which are within ~300 kb of genomic
regions that possess signatures of positive selection, suggesting adaptive
geographical divergence for salt tolerance in this species.
PMID- 27500525
TI - Nucleation of DNA repair factors by FOXA1 links DNA demethylation to
transcriptional pioneering.
AB - FOXA1 functions in epigenetic reprogramming and is described as a 'pioneer
factor'. However, exactly how FOXA1 achieves these remarkable biological
functions is not fully understood. Here we report that FOXA1 associates with DNA
repair complexes and is required for genomic targeting of DNA polymerase beta
(POLB) in human cells. Genome-wide DNA methylomes demonstrate that the FOXA1 DNA
repair complex is functionally linked to DNA demethylation in a lineage-specific
fashion. Depletion of FOXA1 results in localized reestablishment of methylation
in a large portion of FOXA1-bound regions, and the regions with the most
consistent hypermethylation exhibit the greatest loss of POLB and are represented
by active promoters and enhancers. Consistently, overexpression of FOXA1 commits
its binding sites to active DNA demethylation in a POLB-dependent manner.
Finally, FOXA1-associated DNA demethylation is tightly coupled with estrogen
receptor genomic targeting and estrogen responsiveness. Together, these results
link FOXA1-associated DNA demethylation to transcriptional pioneering by FOXA1.
PMID- 27500526
TI - Spatial-Temporal Study of Rab1b Dynamics and Function at the ER-Golgi Interface.
AB - The GTPase Rab1b is involved in ER to Golgi transport, with multiple Rab1b
effectors (located at ERES, VTCs and the Golgi complex) being required for its
function. In this study, we performed live-cell dual-expression studies to
analyze the dynamics of Rab1b and some effectors located at the ERES-Golgi
interface. Rab1b occupied widely distributed mobile punctate and tubular
structures, displaying a transient overlaps with its effectors and showing that
these overlaps occurred at the same time in spatially distinct steps of ER to
Golgi transport. In addition, we assessed Rab1b dynamics during cargo sorting by
analyzing the concentration at ERES of a Golgi protein (SialT2-CFP) during
Brefeldin A washout (BFA WO). Rab1b was associated to most of the ERES
structures, but at different times during BFA WO, and recurrently SialT2-CFP was
sorted in the ERES-Rab1b positive structures. Furthermore, we reveal for first
time that Rab1b localization time at ERES depended on GBF1, a Rab1b effector that
acts as the guanine nucleotide exchange factor of Arf1, and that Rab1b membrane
association/dissociation dynamics at ERES was dependent on the GBF1 membrane
association and activity, which strongly suggests that GBF1 activity modulates
Rab1b membrane cycling dynamic.
PMID- 27500523
TI - Variation in the glucose transporter gene SLC2A2 is associated with glycemic
response to metformin.
AB - Metformin is the first-line antidiabetic drug with over 100 million users
worldwide, yet its mechanism of action remains unclear. Here the Metformin
Genetics (MetGen) Consortium reports a three-stage genome-wide association study
(GWAS), consisting of 13,123 participants of different ancestries. The C allele
of rs8192675 in the intron of SLC2A2, which encodes the facilitated glucose
transporter GLUT2, was associated with a 0.17% (P = 6.6 * 10(-14)) greater
metformin-induced reduction in hemoglobin A1c (HbA1c) in 10,577 participants of
European ancestry. rs8192675 was the top cis expression quantitative trait locus
(cis-eQTL) for SLC2A2 in 1,226 human liver samples, suggesting a key role for
hepatic GLUT2 in regulation of metformin action. Among obese individuals, C
allele homozygotes at rs8192675 had a 0.33% (3.6 mmol/mol) greater absolute HbA1c
reduction than T-allele homozygotes. This was about half the effect seen with the
addition of a DPP-4 inhibitor, and equated to a dose difference of 550 mg of
metformin, suggesting rs8192675 as a potential biomarker for stratified medicine.
PMID- 27500527
TI - Correction: Analysis of Plasma Protein Concentrations and Enzyme Activities in
Cattle within the Ex-Evacuation Zone of the Fukushima Daiichi Nuclear Plant
Accident.
AB - [This corrects the article DOI: 10.1371/journal.pone.0155069.].
PMID- 27500528
TI - Erratum to: "Metabolic Syndrome after Hematopoietic Cell Transplantation: At the
Intersection of Treatment Toxicity and Immune Dysfunction" [Biol Blood Marrow
Transplant 2016;22:1159-1166].
PMID- 27500530
TI - One-step microwave synthesis of N-doped hydroxyl-functionalized carbon dots with
ultra-high fluorescence quantum yields.
AB - A one-step microwave synthesis of N-doped hydroxyl-functionalized carbon dots
(CDs) with ultra-high fluorescence quantum yields (QYs) of 99% is reported. These
ultra-high QY CDs were synthesized using citric acid and amino compound
containing hydroxyls like ethanolamine and tris(hydroxylmethyl)aminomethane.
Amino and carboxyl moieties can form amides through dehydration condensation
reactions, and these amides act as bridges between carboxyl and hydroxyl groups,
and modify hydroxyl groups on the surface of the CDs. The entire reaction can be
carried out within 5 min. When the molar ratio of reactants is 1 : 1, the
hydroxyl and graphitic nitrogen content is the highest, and the synergy leads to
a high ratio between the radiative transition rate and nonradiative transition
rate as well as a high QY. The developed pathway to N-doped hydroxyl
functionalized CDs can provide unambiguous and remarkable insights into the
design of highly luminescent functionalized carbon dots, and expedite the
applications of CDs.
PMID- 27500529
TI - MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing
Radiation.
AB - The radioprotective capacity of a rationally-designed Mn2+-decapeptide complex
(MDP), based on Mn antioxidants in the bacterium Deinococcus radiodurans, was
investigated in a mouse model of radiation injury. MDP was previously reported to
be extraordinarily radioprotective of proteins in the setting of vaccine
development. The peptide-component (DEHGTAVMLK) of MDP applied here was selected
from a group of synthetic peptides screened in vitro for their ability to protect
cultured human cells and purified enzymes from extreme damage caused by ionizing
radiation (IR). We show that the peptides accumulated in Jurkat T-cells and
protected them from 100 Gy. MDP preserved the activity of T4 DNA ligase exposed
to 60,000 Gy. In vivo, MDP was nontoxic and protected B6D2F1/J (female) mice from
acute radiation syndrome. All irradiated mice treated with MDP survived exposure
to 9.5 Gy (LD70/30) in comparison to the untreated mice, which displayed 63%
lethality after 30 days. Our results show that MDP provides early protection of
white blood cells, and attenuates IR-induced damage to bone marrow and
hematopoietic stem cells via G-CSF and GM-CSF modulation. Moreover, MDP mediated
the immunomodulation of several cytokine concentrations in serum including G-CSF,
GM-CSF, IL-3 and IL-10 during early recovery. Our results present the necessary
prelude for future efforts towards clinical application of MDP as a promising IR
countermeasure. Further investigation of MDP as a pre-exposure prophylactic and
post-exposure therapeutic in radiotherapy and radiation emergencies is warranted.
PMID- 27500531
TI - Genome Sequence of the Edible Cultivated Mushroom Lentinula edodes (Shiitake)
Reveals Insights into Lignocellulose Degradation.
AB - Lentinula edodes, one of the most popular, edible mushroom species with a high
content of proteins and polysaccharides as well as unique aroma, is widely
cultivated in many Asian countries, especially in China, Japan and Korea. As a
white rot fungus with lignocellulose degradation ability, L. edodes has the
potential for application in the utilization of agriculture straw resources.
Here, we report its 41.8-Mb genome, encoding 14,889 predicted genes. Through a
phylogenetic analysis with model species of fungi, the evolutionary divergence
time of L. edodes and Gymnopus luxurians was estimated to be 39 MYA. The
carbohydrate-active enzyme genes in L. edodes were compared with those of the
other 25 fungal species, and 101 lignocellulolytic enzymes were identified in L.
edodes, similar to other white rot fungi. Transcriptome analysis showed that the
expression of genes encoding two cellulases and 16 transcription factor was up
regulated when mycelia were cultivated for 120 minutes in cellulose medium versus
glucose medium. Our results will foster a better understanding of the molecular
mechanism of lignocellulose degradation and provide the basis for partial
replacement of wood sawdust with agricultural wastes in L. edodes cultivation.
PMID- 27500532
TI - Identification of Rare Bacterial Pathogens by 16S rRNA Gene Sequencing and MALDI
TOF MS.
AB - There are a number of rare and, therefore, insufficiently described bacterial
pathogens which are reported to cause severe infections especially in
immunocompromised patients. In most cases only few data, mostly published as case
reports, are available which investigate the role of such pathogens as an
infectious agent. Therefore, in order to clarify the pathogenic character of such
microorganisms, it is necessary to conduct epidemiologic studies which include
large numbers of these bacteria. The methods used in such a surveillance study
have to meet the following criteria: the identification of the strains has to be
accurate according to the valid nomenclature, they should be easy to handle
(robustness), economical in routine diagnostics and they have to generate
comparable results among different laboratories. Generally, there are three
strategies for identifying bacterial strains in a routine setting: 1) phenotypic
identification characterizing the biochemical and metabolic properties of the
bacteria, 2) molecular techniques such as 16S rRNA gene sequencing and 3) mass
spectrometry as a novel proteome based approach. Since mass spectrometry and
molecular approaches are the most promising tools for identifying a large variety
of bacterial species, these two methods are described. Advances, limitations and
potential problems when using these techniques are discussed.
PMID- 27500533
TI - Quantification of Boat Visitation Rates at Artificial and Natural Reefs in the
Eastern Gulf of Mexico Using Acoustic Recorders.
AB - Artificial reefs are commonly used as a management tool, in part to provide
ecosystem services, including opportunities for recreational fishing and diving.
Quantifying the use of artificial reefs by recreational boaters is essential for
determining their value as ecosystem services. In this study, four artificial
natural reef pairs in the eastern Gulf of Mexico (off western Florida) were
investigated for boat visitation rates using autonomous acoustic recorders.
Digital SpectroGram (DSG) recorders were used to collect sound files from April
2013 to March 2015. An automatic detection algorithm was used to identify boat
noise in individual files using the harmonic peaks generated by boat engines, and
by comparing the sound amplitude of each file with surrounding files. In all four
pairs, visitation rates were significantly higher at the artificial reef than the
natural reef. This increase in boat visitation was likely due to actual or
perceived increased quality of fishing and diving at the artificial reefs, or to
lack of knowledge of the presence or locations of the natural reefs. Inshore
reefs (<15 m depth) had high variability in monthly visitation rates, which were
generally highest in warmer months. However the seasonal signal was dampened on
offshore reefs (>25 m depth). This study appears to be the first to use acoustic
data to measure participant use of boating destinations, and highlights the
utility of acoustic monitoring for the valuation of this important ecosystem
service provided by artificial reefs.
PMID- 27500534
TI - Correction: alpha-MSH Stimulates Glucose Uptake in Mouse Muscle and
Phosphorylates Rab-GTPase-Activating Protein TBC1D1 Independently of AMPK.
AB - [This corrects the article DOI: 10.1371/journal.pone.0157027.].
PMID- 27500535
TI - Early stage thymoma: is VATS the new standard of care?
PMID- 27500536
TI - De novo mutations in genes of mediator complex causing syndromic intellectual
disability: mediatorpathy or transcriptomopathy?
AB - BACKGROUND: Mutations in the X-linked gene MED12 cause at least three different,
but closely related, entities of syndromic intellectual disability. Recently, a
new syndrome caused by MED13L deleterious variants has been described, which
shows similar clinical manifestations including intellectual disability,
hypotonia, and other congenital anomalies. METHODS: Genotyping of 1,256 genes
related with neurodevelopment was performed by next-generation sequencing in
three unrelated patients and their healthy parents. Clinically relevant findings
were confirmed by conventional sequencing. RESULTS: Each patient showed one de
novo variant not previously reported in the literature or databases. Two
different missense variants were found in the MED12 or MED13L genes and one
nonsense mutation was found in the MED13L gene. CONCLUSION: The phenotypic
consequences of these mutations are closely related and/or have been previously
reported in one or other gene. Additionally, MED12 and MED13L code for two
closely related partners of the mediator kinase module. Consequently, we propose
the concept of a common MED12/MED13L clinical spectrum, encompassing Opitz
Kaveggia syndrome, Lujan-Fryns syndrome, Ohdo syndrome, MED13L haploinsufficiency
syndrome, and others.
PMID- 27500538
TI - Overlapping meta-analyses of bioresorbable vascular scaffolds versus everolimus
eluting stents: bringing clarity or confusion?
PMID- 27500539
TI - Comment on "Evaluation of Antiviral Therapy Performed after Curative Therapy in
Patients with HBV-Related Hepatocellular Carcinoma: An Updated Meta-Analysis".
PMID- 27500537
TI - What is the identity of fibroblast-pneumocyte factor?
AB - Glucocorticoid induction of pulmonary surfactant involves a mesenchyme-derived
protein first characterized in 1978 by Smith and termed fibroblast-pneumocyte
factor (FPF). Despite a number of agents having been postulated as being FPF, its
identity has remained obscure. In the past decade, three strong candidates for
FPF have arisen. This review examines the evidence that keratinocyte growth
factor (KGF), leptin or neuregulin-1beta (NRG-1beta) act as FPF or components of
it. As with FPF production, glucocorticoids enhance the concentration of each of
these agents in fibroblast-conditioned media. Moreover, each stimulates the
synthesis of surfactant-associated phospholipids and proteins in type II
pneumocytes. Further, some have unique activities, for example, KGF also
minimizes lung injury through enhanced epithelial cell proliferation and NRG
1beta enhances surfactant phospholipid secretion and beta-adrenergic receptor
activity in type II cells. However, even though these agents have attributes in
common with FPF, it is inappropriate to specify any one of these agents as FPF.
Rather, it appears that each contributes to separate mesenchymal-epithelial
signaling mechanisms involved in different aspects of lung development. Given
that the production of pulmonary surfactant is essential for postnatal survival,
it is reasonable to suggest that several mechanisms independently regulate
surfactant synthesis.
PMID- 27500540
TI - Repair of Morgagni Hernia in Adults with Primary Closure and Mesh Placement:
First Robotic Experience.
AB - INTRODUCTION: Morgagni hernia (MH) is an uncommon type of diaphragmatic hernia,
especially in adults. Laparoscopic or thorascopic approaches have been described
in adults. There are few reported cases using the Da Vinci robot in children and
no previously described cases in adults. We report our early experience and
technique using the robotic approach for MH repair in adults and its potential
advantages. METHOD: Robotic repair of MH was performed in 3 female patients. Four
trocars were used to gain access to the abdomen. The hernia contents were
reduced, the sac excised, and the defect closed primarily. A 4 * 6 inch
bioabsorbable coating mesh was used in 2 patients and a biologic mesh in 1 for
reinforcement. RESULTS: Robotic repair of MH was technically successful in all 3
patients. The average operative time was 199.3 minutes, and difficult hernia
exposure in one case caused prolonged surgical time. There were no intraoperative
complications. Additional interventions, including a repair of a transverse colon
serosal tear during the reduction of hernia contents, occurred in 1 patient. Two
of the 3 female patients were discharged on postoperative day 1, whereas the
other patient was discharged on postoperative day 3. There were no postoperative
complications. CONCLUSION: Robotic MH repair is an alternative minimally invasive
approach for adults that allows for precise sac excision and primary tension-free
repair with mesh reinforcement.
PMID- 27500541
TI - Quorum sensing and other collective regenerative behavior in organ populations.
AB - Stem cell and microenvironment molecular interactions have been studied in detail
but regenerative behavior at the organ population level has remained unexplored.
Organ renewal can occur continuously or in cyclic episodes. Progenitors may be
distributed as one entity or compartmentalized into multiple units. Multiple
units offer advantages as each unit can be regulated differently in different
body regions or physiological stages, adapting animals to their niche with
flexible functional forms. Using the hair paradigm, we show how periodic
patterning can convert one morphogenetic field into many hair germs, how
follicles can be renewed with different cycle times and phenotypes in a region
specific manner, and how new properties, such as regenerative waves and quorum
sensing, emerge to coordinate collective regenerative behavior.
PMID- 27500542
TI - Development of microstructure and mechanical properties during annealing of a
cold-swaged Co-Cr-Mo alloy rod.
AB - In this study, we investigated the evolution of the microstructure and mechanical
properties during annealing of a cold-swaged Ni-free Co-Cr-Mo alloy for
biomedical applications. A Co-28Cr-6Mo-0.14N-0.05C (mass%) alloy rod was
processed by cold swaging, with a reduction in area of 27.7%, and then annealed
at 1173-1423K for various periods up to 6h. The duplex microstructure of the cold
swaged rod consisted of a face-centered cubic gamma-matrix and hexagonal closed
packed epsilon-martensite developed during cold swaging. This structure
transformed nearly completely to the gamma-phase after annealing and many
annealing twin boundaries were observed as a result of the heat treatment. A
small amount of the epsilon-phase was identified in specimens annealed at 1173K.
Growth of the gamma-grains occurred with increasing annealing time at
temperatures >=1273K. Interestingly, the grain sizes remained almost unchanged at
1173K and a very fine grain size of approximately 8MUm was obtained. The
precipitation that occurred during annealing was attributed to the limited grain
coarsening during heat treatment. Consequently, the specimens treated at this
temperature showed the highest tensile strength and lowest ductility among the
specimens prepared. An elongation-to-failure value larger than 30% is sufficient
for the proposed applications. The other specimens treated at higher temperatures
possessed similar tensile properties and did not show any significant variations
with different annealing times. Optimization of the present rod manufacturing
process, including cold swaging and interval annealing heat treatment, is
discussed.
PMID- 27500543
TI - Kinetic Measurement and Real Time Visualization of Somatic Reprogramming.
AB - Somatic reprogramming has enabled the conversion of adult cells to induced
pluripotent stem cells (iPSC) from diverse genetic backgrounds and disease
phenotypes. Recent advances have identified more efficient and safe methods for
introduction of reprogramming factors. However, there are few tools to monitor
and track the progression of reprogramming. Current methods for monitoring
reprogramming rely on the qualitative inspection of morphology or staining with
stem cell-specific dyes and antibodies. Tools to dissect the progression of iPSC
generation can help better understand the process under different conditions from
diverse cell sources. This study presents key approaches for kinetic measurement
of reprogramming progression using flow cytometry as well as real-time monitoring
via imaging. To measure the kinetics of reprogramming, flow analysis was
performed at discrete time points using antibodies against positive and negative
pluripotent stem cell markers. The combination of real-time visualization and
flow analysis enables the quantitative study of reprogramming at different stages
and provides a more accurate comparison of different systems and methods. Real
time, image-based analysis was used for the continuous monitoring of fibroblasts
as they are reprogrammed in a feeder-free medium system. The kinetics of colony
formation was measured based on confluence in the phase contrast or fluorescence
channels after staining with live alkaline phosphatase dye or antibodies against
SSEA4 or TRA-1-60. The results indicated that measurement of confluence provides
semi-quantitative metrics to monitor the progression of reprogramming.
PMID- 27500544
TI - Odor threshold prediction by means of the Monte Carlo method.
AB - A large set of organic compounds (n=906) has been used as a basis to build up a
model for the odor threshold (mg/m(3)). The statistical characteristics of the
best model are the following: n=523, r(2)=0.647, RMSE=1.18 (training set); n=191,
r(2)=0.610, RMSE=1.03, (calibration set); and n=192, r(2)=0.686, RMSE=1.06
(validation set). A mechanistic interpretation of the model is presented as the
lists of statistical promoters of the increase and decrease in the odor
threshold.
PMID- 27500545
TI - Preharvest ultraviolet-C irradiation: Influence on physicochemical parameters
associated with strawberry fruit quality.
AB - Postharvest ultraviolet-C (UV-C) hormesis has been shown effective for the
treatment of the edible part of several horticultural crops such as strawberry
fruit; however, there is a lack of information on its potential preharvest
impact. In the present study three strawberry cultivars (Fragaria * ananassa
Duch. 'Albion', 'Charlotte' and 'Seascape') were exposed to UV-C during two
growth seasons for a period of three weeks. Treatment begins when the first
flowers were wide open and fruits at commercial maturity were harvested within
one week after UV treatment. The physicochemical quality parameters of the fruits
harvested from the treated plants were compared to those of the fruits of the
untreated control plants. Preharvest UV-C treatment tended to increase fruit
firmness in all cultivars with significant differences declared only for 'Albion'
and 'Seascape' in season 2. Fruits from treated plants were generally redder but
a significant difference was observed only for cultivar 'Charlotte' in the second
growing season. Other color attributes were not affected by UV-C, neither were
organic acids, simple sugars, soluble solids content (SSC), titratable acidity
(TA) and pH, although in most cases slight decreases were noticed. Cultivar and
growing season were the factors that mostly influenced on the parameters under
study. The present study show that cumulative preharvest UV-C treatment of 3.6 kJ
m-2 did not adversely affected important strawberry quality parameters.
PMID- 27500546
TI - Lithium Enolates Derived from Pyroglutaminol: Mechanism and Stereoselectivity of
an Azaaldol Addition.
AB - A lithium enolate derived from an acetonide-protected pyroglutaminol undergoes a
highly selective azaaldol addition with (E)-N-phenyl-1-[2
(trifluoromethyl)phenyl]methanimine. The selectivity is sensitive to
tetrahydrofuran (THF) concentration, temperature, and the presence of excess
lithium diisopropylamide base. Rate studies show that the observable
tetrasolvated dimeric enolate undergoes reversible deaggregation, with the
reaction proceeding via a disolvated-monomer-based transition structure. Limited
stereochemical erosion stems from the intervention of a trisolvated-monomer-based
pathway, which is suppressed at low THF concentrations and elevated temperature.
Endofacial selectivity observed with excess lithium diisopropylamide (LDA) is
traced to an intermediate dianion formed by subsequent lithiation of the
monomeric azaaldol adduct, which is characterized as both a dilithio form and a
trilithio dianion-LDA mixed aggregate.
PMID- 27500547
TI - Interleukin-6 gene polymorphisms correlate with the progression of nephropathy in
Chinese patients with type 2 diabetes: A prospective cohort study.
AB - AIMS: Interleukin-6 (IL-6), an inflammatory cytokine, is considered a candidate
gene possibly involved in susceptibility to nephropathy in diabetes. This study
aimed to examine whether IL-6 polymorphisms predict the progression of
nephropathy in a prospective Chinese cohort of patients with type 2 diabetes.
METHODS: A total of 568 type 2 diabetic patients with normoalbuminuria at
baseline were followed up for a mean of 5.3+/-1.5years. Urinary albumin-to
creatinine ratio (ACR) ?30mg/g in two consecutive urine tests were defined as
progression to diabetic nephropathy (n=143). Five polymorphisms of IL-6 gene,
rs1800795, rs1800796, rs1524107, rs2069837, and rs2069840, were genotyped. Cox
proportional hazard models were used to estimate hazard ratio (HR) and 95% CI of
progression to diabetic nephropathy under different genetic models. RESULTS:
Almost all patients (99.6%) carried the rs1800795 GG homozygous genotypes. In the
Cox proportional models adjusted for multiple covariates, the HR under recessive
model was 2.02 for rs1800796 GG (vs. CC+CG, 95% CI: 1.08-3.75, p=0.027), 2.37 for
rs2069837 GG (vs. AA+AG, 95% CI: 1.15-4.87, p=0.019), and 2.08 for rs1524107 CC
(vs. TT+TC, 95% CI: 1.12-3.89, p=0.021). These associations remained significant
for rs1800796 and rs1524107 after correction for multiple testing (alpha=0.017).
Overall, our results suggest that rs1800796 GG and rs1524107 CC homozygous
genotypes may confer a greater risk for development of nephropathy in type 2
diabetes. CONCLUSIONS: IL-6 gene polymorphisms rs1800796 and rs1524107 may serve
as predictors of progression of nephropathy in Chinese patients with type 2
diabetes.
PMID- 27500548
TI - The relationship between adipokines and the onset of type 2 diabetes in middle
aged men: The PRIME study.
AB - AIMS: Epidemiological evidence suggests that adipokines may be associated with
the onset of type 2 diabetes, but the evidence to date is limited and
inconclusive. This study examined the association between adiponectin and leptin
and the subsequent diagnosis of type 2 diabetes in a UK population based cohort
of non-diabetic middle-aged men. METHODS: Baseline serum levels of leptin and
adiponectin were measured in 1839 non-diabetic men aged 50-60years who were
participating in the prospective population-based PRIME study. Over a mean follow
up of 14.7years, new cases of type 2 diabetes were determined from self-reported
clinical information with subsequent validation by general practitioners.
RESULTS: 151 Participants developed type 2 diabetes during follow-up. In Cox
regression models adjusted for age, men in the top third of the leptin
distribution were at increased risk (hazard ratio (HR) 4.27, 95% CI 2.67-6.83)
and men in the top third of the adiponectin distribution at reduced risk (HR
0.24, 95% CI 0.14-0.42) relative to men in the bottom third. However,
significance was lost for leptin after additional adjustment for BMI, waist to
hip ratio, lifestyle factors and biological risk factors, including C-reactive
protein (CRP). Further adjustment for HOMA-IR also resulted in loss of
significance for adiponectin. CONCLUSIONS: This study provides evidence that
adipokines are associated with men's future type 2 diabetes risk but not
independently of other risk factors.
PMID- 27500549
TI - Aspirin for primary prevention of cardiovascular disease in patients with
diabetes: A meta-analysis.
AB - AIMS: Aspirin use for primary prevention of cardiovascular disease (CVD) is
controversial, especially in patients with diabetes. The objective of this meta
analysis was to evaluate aspirin's safety and efficacy for primary prevention of
CVD [fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke,
angina, transient ischemic attack (TIA), peripheral artery disease (PAD) and
revascularization] in patients with diabetes. METHODS: A literature search was
conducted using the terms cardiovascular disease, aspirin, diabetes mellitus to
identify trials of patients with diabetes who received aspirin for primary
prevention of CVD. Study sample size, and ischemic and bleeding events were
extracted and analyzed using RevMan 5.2.7. RESULTS: In total, 6 studies
(n=10,117) met criteria. Aspirin doses ranged from 100mg every other day to 650mg
daily. Follow-up ranged from 3.6 to 10.1years. In patients with diabetes, there
was no difference between aspirin and placebo with respect to the risk of all
cause mortality (OR 0.93, 95% CI 0.81-1.06), or individual atherosclerotic events
compared to placebo. There were no differences in bleeding (OR 2.53, 95% CI 0.77
8.34), GI bleeding (OR 2.14, 95% CI 0.63-7.33) or hemorrhagic stroke rates (OR
0.90, 0.34-2.33) between groups. CONCLUSIONS: It remains unclear whether aspirin
may reduce the occurrence of a first atherosclerotic event or mortality in
patients with diabetes. More research on this use of aspirin in patients with
diabetes is required to supplement currently available research.
PMID- 27500550
TI - Improved Computation of Protein-Protein Relative Binding Energies with the Nwat
MMGBSA Method.
AB - A MMGBSA variant (here referred to as Nwat-MMGBSA), based on the inclusion of a
certain number of explicit water molecules (Nwat) during the calculations, has
been tested on a set of 20 protein-protein complexes, using the correlation
between predicted and experimental binding energy as the evaluation metric.
Besides the Nwat parameter, the effect of the force field, the molecular dynamics
simulation length, and the implicit solvent model used in the MMGBSA analysis
have been also evaluated. We found that considering 30 interfacial water
molecules improved the correlation between predicted and experimental binding
energies by up to 30%, compared to the standard approach. Moreover, the
correlation resulted in being rather sensitive to the force field and, to a minor
extent, to the implicit solvent model and to the length of the MD simulation.
PMID- 27500551
TI - Local heat application for perimenstrual pain and related syndromes.
PMID- 27500552
TI - Development and community-based validation of eight item banks to assess mental
health.
AB - There is a need for precise but brief screening of mental health problems in a
range of settings. The development of item banks to assess depression and anxiety
has resulted in new adaptive and static screeners that accurately assess severity
of symptoms. However, expansion to a wider array of mental health problems is
required. The current study developed item banks for eight mental health
problems: social anxiety disorder, panic disorder, post-traumatic stress
disorder, obsessive-compulsive disorder, adult attention-deficit hyperactivity
disorder, drug use, psychosis and suicidality. The item banks were calibrated in
a population-based Australian adult sample (N=3175) by administering large item
pools (45-75 items) and excluding items on the basis of local dependence or
measurement non-invariance. Item Response Theory parameters were estimated for
each item bank using a two-parameter graded response model. Each bank consisted
of 19-47 items, demonstrating excellent fit and precision across a range of -1 to
3 standard deviations from the mean. No previous study has developed such a broad
range of mental health item banks. The calibrated item banks will form the basis
of a new system of static and adaptive measures to screen for a broad array of
mental health problems in the community.
PMID- 27500553
TI - Coralloid Co2P2O7 Nanocrystals Encapsulated by Thin Carbon Shells for Enhanced
Electrochemical Water Oxidation.
AB - Core-shell nanohybrids containing cheap inorganic nanocrystals and nanocarbon
shells are promising electrocatalysts for water splitting or other renewable
energy options. Despite that great progress has been achieved, biomimetic
synthesis of metal phosphates@nanocarbon core-shell nanohybrids remains a
challenge, and their use for electrocatalytic oxygen evolution reaction (OER) has
not been explored. In this paper, novel nanohybrids composed of coralloid Co2P2O7
nanocrystal cores and thin porous nanocarbon shells are synthesized by
combination of the structural merits of supramolecular polymer gels and a
controllable thermal conversion technique, i.e., temperature programmable
annealing of presynthesized supramolecular polymer gels that contain cobalt salt
and phytic acid under a proper gas atmosphere. Electrocatalytic tests in alkaline
solution show that such nanohybrids exhibit greatly enhanced electrocatalytic OER
performance compared with that of Co2P2O7 nanostructure. At a current density of
10 mA cm(-2), their overpotential is 0.397 V, which is much lower than that of
Co2P2O7 nanostructures, amorphous Co-Pi nanomaterials, Co(PO3)2 nanosheets, Pt/C,
and some reported OER catalysts, and close to that of commercial IrO2. Most
importantly, both of their current density at the overpotential over 0.40 V and
durability are superior to those of IrO2 catalyst. As revealed by a series of
spectroscopic and electrochemical analyses, their enhanced electrocatalytic
performance results from the presence of thin porous nanocarbon shells, which not
only improve interfacial electron penetration or transfer dynamics but also vary
the coordination environment and increase the number of active 5-coordinated
Co(2+) sites in Co2P2O7 cores.
PMID- 27500554
TI - The ACE2 G8790A Polymorphism: Involvement in Type 2 Diabetes Mellitus Combined
with Cerebral Stroke.
AB - BACKGROUND: We aimed to investigate the correlations between ACE2 polymorphisms
and type 2 diabetes mellitus (T2DM) combined with cerebral stroke (CS). METHODS:
A total of 346 patients treated or hospitalized in our hospital were enrolled,
including 181 cases without cerebrovascular complications (T2DM group) and 165
cases combined with CS (T2DM + CS group); 284 healthy individuals were selected
as the control group. PCR-RFLP and ELISA were used to analyze ACE2 G8790A
polymorphisms and serum ACE2 levels, respectively. RESULTS: Significant
differences were observed in the genotype/allele frequency of ACE2 G8790A between
the T2DM + CS and control groups, and the T2DM and T2DM + CS groups, and in the
genotype frequency of ACE2 G8790A between the T2DM and the control groups. The A
allele may increase the risk of T2DM combined with CS. The AA genotype may also
increase the risk of T2DM combined with CS (OR = 3.733, 95%CI = 2.069-6.738; OR =
3.597, 95%CI = 1.884-6.867). Serum ACE2 levels showed statistically significant
differences among the groups. Systolic pressure and diastolic pressure were
protective factors of T2DM combined with CS. CONCLUSION: The ACE2 G8790A
polymorphism in T2DM patients was correlated with CS, and the A allele might be a
risk factor of T2DM combined with CS.
PMID- 27500555
TI - Photosynthetic activity of vascular bundles in Plantago media leaves.
AB - Photosynthetic processes in the leaf lamina and midribs of Plantago media were
investigated using plants grown in high light (HL) or low light (LL) conditions.
The fluorescence parameters, which indicate photochemical/photosynthetic
activity, were different in HL and LL grown plants, but no major differences
between lamina and midribs were found. An OJIP test (chlorophyll a fluorescence
transient induction) of LL grown plants, indicative of the chloroplast electron
transport chain, also showed both tissues to be similar. In HL plants, a partial
blockage of electron flow between QA (the primary plastoquinone electron acceptor
of PSII) and QB (the secondary plastoquinone acceptor of PSII) was found, and
this was less visible in midribs. The effective dissipation of quantum energy per
reaction center (DI0/RC) was similar in both tissues of HL grown plants, while in
the midribs of LL leaves, this process seemed to be less effective. Measurements
of 13C discrimination showed that the midrib tissues of LL and HL leaves
effectively used beta-carboxylation products to accumulate their biomass. Thus,
the well protected activity of electron transport in midribs with their limited
capacity to fix CO2 from the air may indicate the involvement of this tissue in
beta-carboxylation, transport or signaling. Carbon accumulated in roots showed a
lower 13C discrimination value (more negative) than the values observed in
lamina. This could indicate that roots are supplied with assimilates mostly
during the light phase of the day cycle with intensive C3 photosynthesis.
PMID- 27500556
TI - Metabolic acclimation of tetraploid and hexaploid wheats by cold stress-induced
carbohydrate accumulation.
AB - Metabolic acclimation of plants to cold stress may be of great importance for
their growth, survival and crop productivity. The accumulation carbohydrates
associated with cold tolerance (CT), transcript levels for genes encoding related
enzymes along with damage indices were comparatively studied in three genotypes
of bread and durum wheats differing in sensitivity. Two (Norstar, bread wheat and
Gerdish, durum wheat) were tolerant and the other, SRN (durum wheat), was
susceptible to cold stress. During cold stress (-5 degrees C for 24h), the
contents of electrolyte leakage index (ELI) in Norstar and then Gerdish plants
were lower than that of SRN plants, particularly in cold acclimated (CA) plants
(4 degrees C for 14days), confirming lethal temperature 50 (LT50) under field
conditions. Increased carbohydrate abundances in the cases of sucrose, glucose,
fructose, hexose phosphates, fructan, raffinose, arabinose resulted in different
intensities of oxidative stress in bread (Norstar) plants compared to durum
plants (SRN and Gerdish) plants as well as in CA plants compared to non
acclimated (NA) ones under cold, indicating metabolic/regulatory capacity along
with a decrease in ELI content and enhanced defense activities. A significant
decrease in these carbohydrates, particularly sucrose, under cold in NA plants
showed an elevated level of cell damage (confirmed by ELI) compared to CA plants.
On the other hand, an increase in hexose phosphates, particularly in NA plants,
indicated sucrose degradation along with greater production of glucose and
fructose compared to CA plants. Under such conditions, a significant increase in
transcript levels of sucrose synthase and acidic invertase confirmed these
results. Under cold, the high ABA-containing genotypes like Norstar and then
Gerdish, which were obvious in CA plants, partly induced relative acclimation of
cells for acquisition of CT compared to SRN. These results reveal an important
role of carbohydrate metabolism in creating CT in durum wheats (particularly in
Gerdish) as well as bread wheat with possible responsive components in metabolic
and transcript levels.
PMID- 27500558
TI - Molecular cloning of melatonin 3-hydroxylase and its production of cyclic 3
hydroxymelatonin in rice (Oryza sativa).
AB - Melatonin is metabolized in animals to cyclic 3-hydroxymelatonin (3-OHM) not by
an enzymatic pathway, but by interaction with hydroxyl radicals. The production
of 3-OHM in animals suggests the possible presence of 3-OHM in plants. Prior to
the identification of 3-OHM in plants, we directly cloned the corresponding
gene(s) responsible for 3-OHM synthesis using Escherichia coli library strains
expressing genes belonging to the 2-oxoglutarate-dependent dioxygenase (2-ODD)
superfamily from rice. Three of 35 E. coli library strains supplemented with 1
mmol/L melatonin were found to produce 3-OHM in their extracellular medium,
suggestive of three 2-ODD genes involved in 3-OHM production. The purified
recombinant 2-ODD 11, 2-ODD 26, and 2-ODD 33 proteins were shown to catalyze the
metabolism of melatonin to 3-OHM, with 2-ODD 11 showing the highest melatonin 3
hydroxylase (M3H) catalytic activity. Consistent with the presence of M3H genes,
rice leaves supplemented with 5 mmol/L melatonin produced 3-OHM [233 MUg/g fresh
weight (FW)], 2-hydroxymelatonin (21 MUg/g FW), and N1 -acetyl-N2 -formyl-5
methoxykynuramine (5 MUg/g FW). Three M3H transcripts were induced upon the
treatment of rice leaves with cadmium followed by an increase in M3H enzyme
activity. Cloning of M3H genes in plants has paved the way for the studies of
melatonin in plants in terms of its multiple physiological roles.
PMID- 27500559
TI - Prospective pilot study to detect dogs with non food-induced canine atopic
dermatitis using Fourier transform infrared spectroscopy.
AB - BACKGROUND: The diagnosis of canine atopic dermatitis (CAD) remains challenging
due to the lack of a simple biomarker or metabolic profile. In human medicine,
Fourier transform infrared spectroscopy (FTIR) is an analytical technique used
for several diseases. It requires a small amount of sample and allows the
identification of structural moieties of biomolecules on the basis of their
infrared absorption, with limited sample pretreatment. HYPOTHESIS/OBJECTIVES: The
aim of the study was to evaluate the diagnostic value of FTIR. ANIMALS: Three
groups were tested: 21 dogs with non food-induced CAD (NFICAD), 16 dogs with
inflammatory conditions of various origins but without allergic dermatoses (OD)
and 10 healthy dogs (H). METHODS: Peripheral blood was collected and spectra were
acquired with a FTIR spectrophotometer. A principal component analysis (PCA) was
performed on the full wavenumber spectra (4000-600/cm), followed by a Fisher
discriminant analysis (DA) to assess the differences between the three groups.
RESULTS: The PCA followed by the DA of whole spectra showed significant
differences between the three groups. These results suggest that by using the
FTIR method, dogs with NFICAD can be differentiated from healthy dogs and dogs
with nonallergic inflammation. There was no overlap between the spectral data of
the three groups indicating that NFICAD dogs were correctly segregated from the H
and OD groups. CONCLUSIONS: A study on a larger cohort including common pruritic
skin diseases is necessary to confirm these initial results and the relevance of
this diagnostic technique.
PMID- 27500557
TI - A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable
Assessment of Functional Recovery Resulting From Nerve Regeneration.
AB - Improved nerve regeneration and functional outcomes would greatly enhance the
utility of vascularized composite allotransplantation (VCA) such as hand and
upper extremity transplantation. However, research aimed at achieving this goal
has been limited by the lack of a functional VCA animal model. We have developed
a novel rat midhumeral forelimb transplant model that allows for the
characterization of upper extremity functional recovery following
transplantation. At the final end point of 12 weeks, we found that animals with
forelimb transplantation including median, ulnar and radial nerve coaptation
demonstrated significantly improved grip strength and forelimb function as
compared to forelimb transplantation without nerve approximation (grip strength:
1.71N +/- 0.57 vs. no appreciable recovery; IBB scale: 2.6 +/- 0.7? vs. 0.8 +/-
0.40; p = 0.0005), and similar recovery to nerve transection-and-repair only
(grip strength: 1.71N +/- 0.57 vs. 2.03 +/- 0.42.6; IBB scale: 2.6 +/- 0.7 vs.
2.8 +/- 0.8; p = ns). Moreover, all forelimb transplant animals with nerve
coaptation displayed robust axonal regeneration with myelination and reduced
flexor muscle atrophy when compared to forelimb transplant animals without nerve
coaptation. In conclusion, this is the first VCA small-animal model that allows
for reliable and reproducible measurement of behavioral functional recovery in
addition to histologic evaluation of nerve regeneration and graft reinnervation.
PMID- 27500560
TI - Highly Stable, Functional Hairy Nanoparticles and Biopolymers from Wood Fibers:
Towards Sustainable Nanotechnology.
AB - Nanoparticles, as one of the key materials in nanotechnology and nanomedicine,
have gained significant importance during the past decade. While metal-based
nanoparticles are associated with synthetic and environmental hassles, cellulose
introduces a green, sustainable alternative for nanoparticle synthesis. Here, we
present the chemical synthesis and separation procedures to produce new classes
of hairy nanoparticles (bearing both amorphous and crystalline regions) and
biopolymers based on wood fibers. Through periodate oxidation of soft wood pulp,
the glucose ring of cellulose is opened at the C2-C3 bond to form 2,3-dialdehyde
groups. Further heating of the partially oxidized fibers (e.g., T = 80 degrees
C) results in three products, namely fibrous oxidized cellulose, sterically
stabilized nanocrystalline cellulose (SNCC), and dissolved dialdehyde modified
cellulose (DAMC), which are well separated by intermittent centrifugation and co
solvent addition. The partially oxidized fibers (without heating) were used as a
highly reactive intermediate to react with chlorite for converting almost all
aldehyde to carboxyl groups. Co-solvent precipitation and centrifugation resulted
in electrosterically stabilized nanocrystalline cellulose (ENCC) and
dicarboxylated cellulose (DCC). The aldehyde content of SNCC and consequently
surface charge of ENCC (carboxyl content) were precisely controlled by
controlling the periodate oxidation reaction time, resulting in highly stable
nanoparticles bearing more than 7 mmol functional groups per gram of
nanoparticles (e.g., as compared to conventional NCC bearing << 1 mmol functional
group/g). Atomic force microscopy (AFM), transmission electron microscopy (TEM),
and scanning electron microscopy (SEM) attested to the rod-like morphology.
Conductometric titration, Fourier transform infrared spectroscopy (FTIR), nuclear
magnetic resonance (NMR), dynamic light scattering (DLS), electrokinetic-sonic
amplitude (ESA) and acoustic attenuation spectroscopy shed light on the superior
properties of these nanomaterials.
PMID- 27500561
TI - Insurance status and disparities in disease presentation, treatment, and outcomes
for men with germ cell tumors.
AB - BACKGROUND: People aged 26 to 34 years represent the greatest proportion of the
uninsured, and they have the highest incidence of testicular cancers. The aim of
this study was to investigate the association between insurance status and cancer
outcomes in men diagnosed with germ cell tumors. METHODS: The Surveillance,
Epidemiology, and End Results database was used to identify 10,211 men diagnosed
with germ cell gonadal neoplasms from 2007 to 2011. Associations between
insurance status and characteristics at diagnosis and receipt of treatment were
examined with log-binomial regression. The association between insurance status
and mortality was assessed with Cox proportional hazards regression. RESULTS:
Uninsured patients had an increased risk of metastatic disease at diagnosis
(relative risk [RR], 1.26; 95% confidence interval [CI], 1.15-1.38) in comparison
with insured patients, as did Medicaid patients (RR, 1.62; 95% CI, 1.51-1.74).
Among men with metastatic disease, uninsured and Medicaid patients were more
likely to be diagnosed with intermediate/poor-risk disease (RR for uninsured
patients, 1.22; 95% CI, 1.04-1.44; RR for Medicaid patients, 1.39; 95% CI, 1.23
1.57) and were less likely to undergo lymph node dissection (RR for uninsured
patients, 0.74; 95% CI, 0.57-0.94; RR for Medicaid patients, 0.76; 95% CI, 0.63
0.92) in comparison with insured patients. Men without insurance were more likely
to die of their disease (hazard ratio [HR], 1.88; 95% CI, 1.29-2.75) in
comparison with insured men, as were those with Medicaid (HR, 1.51; 95% CI, 1.08
2.10). CONCLUSIONS: Patients without insurance and patients with Medicaid have an
increased risk of presenting with advanced disease and dying of the disease in
comparison with those who have insurance. Future studies should examine whether
implementation of the Patient Protection and Affordable Care Act reduces these
disparities. Cancer 2016;122:3127-35. (c) 2016 American Cancer Society.
PMID- 27500562
TI - A Vinylene-Bridged Perylenediimide-Based Polymeric Acceptor Enabling Efficient
All-Polymer Solar Cells Processed under Ambient Conditions.
AB - All-polymer solar cells with 7.57% power conversion efficiency are achieved via a
new perylenediimide-based polymeric acceptor. Furthermore, the device processed
in ambient air without encapsulation can still reach a high power conversion
efficiency (PCE) of 7.49%, which is a significant economic advantage from an
industrial processing perspective. These results represent the highest PCE
achieved from perylenediimide-based polymers.
PMID- 27500563
TI - Expanding our digital archives.
PMID- 27500564
TI - Authors' reply.
PMID- 27500565
TI - Kshitish Chandra Saha (January 1, 1930 - June 3, 2016).
PMID- 27500566
TI - Fatty-acid biomarkers and tissue-specific turnover: validation from a controlled
feeding study in juvenile Atlantic croaker Micropogonias undulatus.
AB - Fatty-acid (FA) profiles of liver and muscle tissue from juvenile Atlantic
croaker Micropogonias undulatus were examined over a 15 week diet-switch
experiment to establish calibration coefficients (CC) and improve understanding
of consumer-diet relationships for field applications. Essential FAs
[docosahexaenoic acid (DHA), 22:6n-3 and eicosapentaenoic acid (EPA) , 20:5n-3]
decreased and 18:2n-6 increased in tissues of M. undulatus fed diets with
increasing proportions of terrestrial v. marine lipid sources. Non-linear models
used to estimate the incorporation rate and days to saturation of per cent 18:2n
6 in tissues showed that livers incorporated 18:2n-6 faster than muscle, but the
proportions of 18:2n-6 in muscle were higher. CCs were established to determine
proportions of FA deposition in tissues relative to diet. Many CCs were
consistent amongst diet treatments, despite growth and dietary differences. The
CCs can be used to discern FA modification and retention within tissues and as
tools for future quantitative estimates of diet histories. Incorporation rates
and CCs of 18:2n-6 were applied to a sub-set of field samples of wild M.
undulatus to understand habitat use and feeding ecology. Altogether, these
results suggest that FAs provide a time-integrated measure of diet in aquatic
food webs and are affected by tissue type, growth rate and the influence of mixed
diets.
PMID- 27500567
TI - Dynamics of gyrification in the human cerebral cortex during development.
AB - This study quantitatively characterized cortical gyrus folding over human
neocortical development by calculating the gyrification index (GI) in 22 human
fetal specimens from 16 to 40 weeks with magnetic resonance imaging data. GI
values remained constant at approximately 1.0 until the fetal specimens reached
500 g body weight and 200 mm crown-rump length (CRL), respectively, and then
increased in correlation with the body weight and CRL. The rostrocaudal GI
distribution in the cerebral cortex revealed a correspondence of GI peaks with
indentations of early-generated primary sulci at 21 weeks of gestation and more
frequently increased GI values in the parieto-occipital region than in the fronto
temporal region at 31 and 40 weeks of gestation. These results provide a
quantitative reference set for gyrification in normal human cortical development,
which may help reveal the mechanism of neurodevelopmental disorders.
PMID- 27500568
TI - Crystal structure of Arabidopsis thaliana calmodulin7 and insight into its mode
of DNA binding.
AB - Calmodulin (CaM) is a Ca(2+) sensor that participates in several cellular
signaling cascades by interacting with various targets, including DNA. It has
been shown that Arabidopsis thaliana CaM7 (AtCaM7) interacts with Z-box DNA and
functions as a transcription factor [Kushwaha R et al. (2008) Plant Cell 20, 1747
1759; Abbas N et al. (2014) Plant Cell 26, 1036-1052]. The crystal structure of
AtCaM7, and a model of the AtCAM7-Z-box complex suggest that Arg-127 determines
the DNA-binding ability by forming crucial interactions with the guanine base. We
validated the model using biolayer interferometry, which confirmed that AtCaM7
interacts with Z-box DNA with high affinity. In contrast, the AtCaM2/3/5 isoform
does not show any binding, although it differs from AtCaM7 by only a single
residue.
PMID- 27500569
TI - [Department of Otorhinolaryngology of the I.P. Pavlov Saint-Peterburg First State
Medical University].
AB - This article is designed to report the results of the analysis ofacademic,
scientific, and clinical activities of the Department of Otorhinolaryngology of
the I.P. Pavlov Saint-Peterburg First State Medical University.
PMID- 27500570
TI - [The potential of cone beam computed tomography of the temporal bones in the
patients presenting with otosclerosis].
AB - The objective of the present study was to analyze the potential of cone beam
computed tomography of the temporal bones in the patients presenting with
otosclerosis for the detection of surgically significant specific structural
features of the labyrinth wall of the tympanic cavity. More than 400 tomograms of
the temporal bones were obtained with the use of a cone beam tomographwere
available for the investigation during the period from 2012 till 2016. The study
was carried out in several steps, viz. the search for the optimal (for the given
instrument) position of the patient, the experimental stage, the retrospective
analysis of the tomograms and the comparison of the temporal bones of different
types (pneumatic, mixed, and sclerotic) in individual patients, the comparison of
the results of cone beam computed tomography (CBCT) with the intraoperative
observations, and the modification of the algorithm for the analysis of temporal
bone cone beam tomograms. The study included a total of 16 patients (15 women at
the age from 32 to 56 years and one managed 58 years) presenting with the
clinical diagnosis of otosclerosis. The results of the study were used to
elaborate the algorithm for the analysis of cone beam tomograms of the temporal
bones to be performed inthe stage by stage manner including the qualitative
analysis of tomograms, evaluation of their quantitative parameters and additional
characteristics to be taken into consideration when planning the surgical
interventions on the labyrinth wall and the tympanic cavity as a preparation for
the stapedoplastic treatment. The results of CBCT obtained in the present study
were compared with the surgical observations. The diagnostic sensitivity and
specificity of the method were estimated to be 100% and 83% respectively. It is
concluded that cone beam computed tomography can be employed as a component of
the diagnostic algorithm prior to the planning of surgical interventions onthe
medial wall of the tympanic cavity and the assessment of dynamics of the clinical
course of middle ear diseases.
PMID- 27500571
TI - [The choice of parameters for the laser application in ENT surgery].
AB - The authors present the results and describe the methods of the experimental
studies aimed at the evaluation of the biological effects of laser-assisted
treatment of ENT pathologies at the wavelengths of 810 nm, 980 nm, and 1470 nm in
comparison with the results obtained with the use of a radiofrequency scalpel in
biological tissues having different optical and mechanical properties.Special
emphasis is placed on the peculiarities of the action of laser irradiation and
healing of radiation-induced wounds depending on the treatment regimens, viz.
contact, remote, pulsed and continuous ones. The results of the analysis of the
experience gained during the study and of the experimental findings provided a
basis on which the main principles of the choice of the optimal parameters of the
laser radiation action on the biological tissues have been formulated.
PMID- 27500572
TI - [The damage to the trigeminal nerve associated with herpetic viral infection in
otorhinolaryngology].
AB - Neurotropism of herpetic viral infection is attributable to a wide range of its
clinical manifestations. Theobjective of the present study was to elucidate the
specific features of the damage to the trigeminal nerve associated with this
condition. A total of 36 patients presenting with trigeminal nerve
neuropathycaused by type 1 herpes simplex infection and 21 patients with
trigeminal nerve neuropathy due to Herpes zoster oticus infection were available
for the examination and etiopathogenetic treatment. The traditional clinical
methods used in the study were supplemented by virological diagnostics for the
verification of herpetic infection and theelectroneurographic technique. The
apparent clinical recovery was documented for 23 and 11 patients of the former
and latter groups respectively.
PMID- 27500573
TI - [The rationale for the conservative treatment of chronic tonsillitis in the
patients of the older age groups by the "soft" therapy methods].
AB - The objective of the present study was to develop an efficient system for the
treatment of chronic tonsillitis in the patients of advanced and middle age based
on the application of polyvalent bacteriophages in the combination with the
physical factors and herbal medicines. The study involved 65 patients (39 women
and 276 men) at the age from 65 to 73 years presenting with chronic tonsillitis.
The treatment included washing the tonsillar lacunae with herbal infusion
consisting of a tetterwort (Choledoniummajus) extract. This procedure was
followed by phonophoresiswith the use of the combined polyvalent bacteriophage
preparation in the non-liquid formulation during 7-10 days. The effectiveness of
such treatment was evaluated based on the results of clinical examination and the
analysis of the subjective feelings reported by the patients. In addition, the
rosette-forming function of lymphocytes was estimated and palatine tonsil
microbiotas in different patients were compared. The effectiveness of therapy was
estimated at 89.2%. The positive outcome of the proposed treatment was documented
in 78.6% of the cases within 6 months after the onset of therapy. It is concluded
that the treatment of chronic tonsillitis with bacteriophagal preparations and
herbal infusions in combination with thetraditionallow-frequency ultrasound
treatment is highly efficacious (favourable outcome in 78.6% of the patients of
middle and advanced age) without the use of antibiotic medications.
PMID- 27500574
TI - [Determination of the rational extent of laser-assisted resection for the
treatment of paralytic laryngeal stenosis].
AB - The objective of the present study was to improve the procedures for extended and
restricted laser-assisted laryngoplasty in the patients presenting withparalytic
laryngeal stenosis and to evaluate the outcome of the surgical
interventionsdiffering in extent. The study included 51 patients (47 women and 4
men) at the age varying from 18 to 78 years. Twenty five of these patients had a
tracheostoma. The examination was focused on the detection of the following
characteristics: vocal fold angle, body mass index, age, specific anatomical and
physiological features of the larynx, clinically significant concomitant
pathologies, engagement in voice and speech professional activities as well as
the influence of paramedical factors. The resulting total score was calculated.
The data obtained were used to rationally plan the laser-assisted resection
(either extended or restricted)of the posterior third of a vocal fold. The total
score of 6 or higher always implied the necessity of extended resection whereas
the overall score of 3 and less was regarded as an indication for the tissue
sparing surgery. The patients to whom the extended resection was prescribed had
significantly higher physical health indices and the worse vocal function
compared with the same parameters in the patients undergoing restricted
resection. The spirometric characteristics of the patients in both groups were
similar and either normal or slightly reduced. The characteristics of the psychic
component of general health were not significantly different and corresponded to
the internationally accepted normal values. It is concluded that the proposed
treatment resulted in the favourable outcome in 49 of the 51 patients (96%).
PMID- 27500575
TI - [The association of the severe clinical course of respiratory papillomatosis with
certain HLA-DQ alleles].
AB - We undertook the analysis of genetic polymorphism of the HLADQA1 and DQB1 genes
in the patients presenting with recurrent respiratory papillomatosis (n=21) with
the use of the multiprimer polymerase chain reaction. The results of the study
give evidence that the identification of DQ 2.5 and DQ 7.5 haplotypes encoded by
the DQA1 *0501, DQB1 *0201, DQA1 *0505, and DQB1 *0301 alleles as well as the
carriage of type 16 human papilloma virus (HPV) in combination with these
haplotypes in the patients with recurrent respiratory papillomatosis can be used
for the prognostication of the severity of this disease.
PMID- 27500576
TI - [The low-invasive treatment of laryngotrachealstenoses].
AB - The objective of the present study was to evaluate the effectiveness and safety
of balloonlaryngotracheoplasty for the treatment of laryngeal and tracheal
stenosis We undertook the analysis of the case histories of the patients
presenting withlaryngotracheal stenosis who had undergone
balloonlaryngotracheoplasty during the period from October 2013 till February
2016. A total of 21 histories of the patients (6 men and 15 women) were available
for the investigation. Most laryngotrachealstenoses that occurred in 18 (85.7%)
patients were of the idiopathic, post-tracheotomy, and post-intubation types.
Their most typical localization was the subfold part of the larynx and/or the
upper third of the trachea (76.2%). The length of the stenotic lesions varied
from 5 to 20 mm (76.2%) and corresponded to grade III if estimated based on the
Cotton-Myer classification (81%). The number of the balloonlaryngotracheoplastic
procedures ranged from 1 to 4 (a total of 36 operations). The interval between
the consecutive interventions varied from 1.5 to 104 (mean 20) weeks. In 16 of
the 36 cases, dilatation of the narrowed portion was followed by the 4 minute
application of mitomycin C at a concentration of 0.4 mg/kg. No complications were
documented during the surgical interventions and in the postoperative periods.
The treatment was associated with a significant enhancement of the maximum
expiratory flow rate from 2+/-1.13 l/s to 4.23+/-1.9 l/s (p=0.000). The duration
of the follow up period varied from 1 to 105 (mean 36.2) weeks. Mitomycin C
exerted nosignificant influence on the increment of the maximum expiratory flow
rate (p=0.174).
PMID- 27500577
TI - [The blockade of sphenopalatineganglionthrough the palatal approachin the present
day rhinological practice].
AB - This article deals with the application of the sphenopalatine ganglion blockade
in the present-day rhinological practice. The blockade is known to arrest the
propagation of pain impulses from the nose and break the rhinocardiac reflex arc.
Moreover, it is involved in bleeding control during nasal surgery. The method for
the blockade via the palatal route using the modern equipment and imaging
techniques is described. The objective of the present study was to evaluate the
effectiveness and safety of the blockade of sphenopalatine ganglionthrough the
palatal approach in the patients who had undergone septoplasty under general and
local anesthesia. It included a total of 105 patients divided into two groups one
of which was treated with the use ofblockade of sphenopalatineganglionin addition
to conventional anesthesia while the patients of the other group were treated
under traditional anesthesia alone. The results of the study confirm the
effectiveness of blockade of sphenopalatineganglionthrough the palatal approach
as a method for the treatment of postoperative syndrome, bleeding control during
nasal surgery, and reduction of parasympathetic influence on the cardiac rhythm.
PMID- 27500578
TI - [Endoscopic endonasal surgery of paranasal sinus osteomas].
AB - This article was designed to summarize the experience gained withendoscopic
endonasal removal of paranasal sinus osteomas during the period from January 2013
till February 2016. In addition a review of the relevant literature is presented
encompassing the publicationsthat provide information about etiology,
pathogenesis, clinical picture, diagnostics, and treatment of bone tumours. The
objective of the study was to enhance the effectiveness and safety of the
surgical treatment of the patients presenting with paranasal sinus osteomas. A
total of 81 cases of paranasal sinus osteoma were documented in the patients
admitted to I.P. Pavlov Saint-Peterburg First State Medical Universityduring the
period from January 2013 till February 2016. Forty nine of them were given the
surgical endoscopic endonasal treatment with the removal of the neoplasm. The
remaining 32 patients were included in the group for the further dynamic follow
up. The authors report the data of morphological studies and the results of
computed tomography performed in the pre- and postoperative periods with special
reference to the potential for the use of the electromagnetic navigation station
(an image-guidance system) that makes it possible to significantly reduce the
risk of development of possible complications. In addition, the findings
suggestive of the progressive tumour growth in the group of the patients under
dynamic observation are discussed.
PMID- 27500580
TI - [Differential diagnostics of the causes responsible for a cough in the pregnant
women].
AB - The objective of the present study was to elucidate the causes responsible for a
cough in the pregnant women. It involved 92 patients including 23 ones presenting
with bronchial asthma and 69 having no manifestations of asthma in their medical
histories but suffering from dry cough that started after the beginning of
pregnancy. All the patients were given counseling by the otorhinolaryngology and
pulmonology specialists. The degree of endoscopic manifestations of
gastroesophageal reflux was estimated based on a scoring scale. The study
revealed the correlation between cough duration and gestational age. The signs of
reflux-induced changes in the larynx were documented in 91% cases among the
patients with bronchial asthma and in 97% cases in the pregnant women having no
bronchial pathology in their medical histories. The main cause behind the cough
during pregnancy in women without bronchial pathology was sluggish bronchitis
(7%), arising asthma (12%), gastroesophageal reflux (77%), and allergic rhinitis
(4%). This conclusion was confirmed by the results of therapy.
PMID- 27500579
TI - [Local cytokine therapy of inflammation of the rhinosinusotubal area].
AB - The objective of the present work was to elaborate a scheme for the effective
combined treatment ofinflammation of the rhinosinusotubal area including the
local administration of roncoleukin and cyclopheron without antibiotics. The
study included 82 patients (27 men and 55 women) at the age from 25 to 55 years
presenting with acute inflammation ofroncoleukin and cycloferon. They were
divided into two groups. Group 1 was comprised of 39 patients dominated by those
with the clinical picture of sinusitis whereas group 2 contained 43 patients in
whom symptoms of catarrhal otitis media prevailed. The patients of both groups
were treated by the local application of roncoleukin in combination with
cycloferon inhalation, intranasal administration of decongestants and
mucomodifiers. All the patients underwent, before and after the treatment, the
microbiological study of the contents of the sinuses, impedancobarometry, 3D
computed tomography, and measurement of the IgA, IgM, IgG, IgE, SIgA, IL-8, TNF
alpha, and albumin levels in the blood sera and lavages. The study has
demonstrated the difference between the local cytokine levels in the two groups
of the patients. The clinical improvement was documented within 24 hours after
the onset of therapy. 93.3% of the patients recovered by day 5. Three (3.7%) of
them had to be prescribed antibiotic therapy for the lack of the desired effect
of the cytokine treatment. It is concluded that the local application of
ronkoleukin and cycloferon in combination with elimination therapy provides a
tool for the efficient treatment of the patients suffering frominflammatory
pathology of the rhinosinusotubalzone due to its stimulatory action on the immune
system at the inflammation site mediated through the activation of the earlier
formed targeted immune response, the promotion of the accelerated elimination of
the causative factor, and the termination of the pathological process.
PMID- 27500581
TI - [The systemic approach to the rehabilitation of the patients presenting with
laryngeal cancer after the resection of the organ and laryngectomy with
tracheoesophageal by-pass and endoprosthetics].
AB - The objective of the present study was to enhance the effectiveness of
rehabilitation of the patients presenting with laryngeal cancer after the
resection of the organ and laryngotomy with tracheoesophageal by-pass and
endoprosthetics. Our experience in this field is based on the treatment of 102
patients. They were distributed by the nosological forms as follows: primary
laryngeal cancer in 97 patients including T1NoMo - 8 (8.2%), T2NoMo - 63 (65%),
T3NoMo - 18 (17.6%), T2N1Mo - 1 (0.9%), T4NoMo - 3 (2.9%), and T4N1M0 - 4 (3.9%),
root of the tongue cancer spreading over the vestibular part of the larynx in one
patient, laryngeal sarcoma in one patient, relapse of cancer following the full
dose radiotherapy and organ-sparing surgery in 3 patients. Laryngeal resection
was performed in 83 patients; 19 patients underwent laryngectomy with
tracheoesophageal by-pass and endoprosthetics using a domestically manufactured
voice prosthesis. The systemic approach to the rehabilitation of the patients and
the use of the proposed treatment algorithm made it possible to restore the
function of the larynx by means of organ-sparing surgery in 79 (95.1%) of the 83
patients. The vocal function in the patients following laryngectomy with
tracheoesophageal by-pass and endoprosthetics was restored in 18 (94.7%) of the
19 patients.
PMID- 27500582
TI - [Clinico-anamnestic diagnostics of chronic maxillary sinusitis associated with
chlamydial infection].
AB - The present study included 201 adult patients presenting with exacerbation of
chronic maxillary sinusitis. The presence of Chlamydia trachomatis and Chl.
pneumoniae was verified by the direct immunofluorescencetechnique and polymerase
chain reaction. The study material consisted of swipes und swabs from the mucous
membrane of the middle nasal passage. The information from the patients was
collected with the use of a questionnaire specially elaborated for the purpose of
this study. The correlation relationships were established by means of gamma
statistics. The method is based on the calculation of the integral index
characterizing the risk of development of chlamydial infection using the scoring
scale for the evaluation of the clinical and anamnestic characteristics of the
patients. The assessment of the risk of chlamydial colonization by the anamnestic
method makes it possible to enhance the effectiveness of clinical diagnostics of
chlamydial infection and thereby provides a basis for the prescription of the
adequate anti-chlamydial treatment facilitating reduction of the frequency of
complications and preventing dissemination of the causative factor of the
disease. Moreover, this approach creates the conditions for the targeted
selection of the patients to be referred to the laboratory verification of
Chlamydia. Highoperating performance and effectiveness characteristics of the
clinic-anamnestic diagnostics make it a method of choice for the wide application
in the clinical practice.
PMID- 27500583
TI - [The anthropometric parameters of the external nose in a Kazakh population with
particular reference to the planning of ethnic-specific rhinoplasty].
AB - The objective of the present study was to determine the anthropometric parameters
of the external nose in a Kazakh population for the subsequent elaboration of the
algorithms of and approaches to the planning of ethnic-specific rhinoplasty. The
study included 500 ethnic Kazakhs (197 women and 303 men) at the age varying from
16 to 25 (mean 20.6+/-3.5) years. The following parameters were calculated; the
height and the width of the nose, nasal index, lobular index, nasolabial angle,
nasal projection index, projection and rotation of the tip of the nose. It was
found that the nasal index in male and female Kazakhs was 80.8+/-0.53 and 79.4+/
3.17 respectively which corresponds to mesorhinia and is more characteristic of
the Europeoid race. The nasofrontalindex in men andwomen was 138.94+/-5.71 ad
130.1+/-8.25 degrees respectively. Rotation of the tip of the nose in men was
78.45+/-2.24 degrees in men and 73.92+/-4.32 degrees in women. Goode's nasal
projection index was 57.25+/-4.36%. The nasal tip projection was estimated at
67.9+/-5.21 and 76.72+/-4.17 in men and women respectively. It is concluded based
on the results of the present study that noses in Kazakh men and women have
certain specific masculine and feminine anthropometric features making them
different from the typical "Asiatic" noses because some of their proportions are
more characteristic of the Europeoid race. The height of the nose in the Kazakhs
is lowest among the three races. It indicates that the main concern as regards
rhinoplasty in the Kazakh population is the dorsal augmentation. The present
study provided the reference information on the parameters of the external nose
in the Kazakh population that may be of value not only in terms of reconstructive
and aesthetic rhinosurgery but also for the purpose of forensic medical and other
expertises.
PMID- 27500584
TI - The impact of knowledge and religion on organ donation as seen by immigrants in
Sweden.
AB - BACKGROUND: Transplantation of organs is one of the most successful medical
advances of the past 60 years and transplantation is the treatment of choice for
severe organ failure worldwide. Despite this situation, and the general
acknowledgement of organ donation as a global priority, demand for organs
outstrips supply in virtually every country in the world. AIM: The aim of the
study was to elucidate factors that influence immigrant's decisions regarding
organ donation. METHODS: Data were collected through three group interviews using
open-ended questions and qualitative content analysis. 32 participants, 16 men
and 16 women from Bosnia and Herzegovina, Somalia, Lebanon and Kosovo
participated in focus group interviews (FGI). RESULTS: Analysis of the collected
data resulted in two main categories: 'Information about organ donation' and
'Religious aspects of organ donation and a number of subcategories'. Some of the
influencing factors concerning organ donation were mainly related to limited
information from society as well as limited information from healthcare
professionals. Religious aspects, fear and prejudices about organ donation were
other factors that mentioned by participants as hamper regarding organ donation.
CONCLUSION: In order to improve immigrants' attitude towards organ donation,
information about this issue and identification of the hampering factors,
particularly culturally related factors such as the religious aspect, is
essential. In this context, different intervention studies are needed to increase
monitories groups' attitude towards organ donations.
PMID- 27500585
TI - Self-perceived taste disturbance: a 20-year prospective study of a Swedish 1942
birth cohort.
AB - OBJECTIVES: The aim of this study was to assess the impact of dental care
factors, general health factors and socio-economic factors on perceived taste
disturbance (PTD) over time and to assess the stability of or change in PTD in a
panel of individuals as they progressed from middle age (50 years) to early old
age (70 years). MATERIALS AND METHODS: Data collection was conducted from a
cohort study beginning in 1992, when the participants were 50 years old, and
again 5, 10, 15 and 20 years later. Stability and change in PTD were described
using cross-tabulation. Perceived taste disturbance over the 20-year survey
period was modelled using the generalised estimating equation (GEE). RESULTS: The
prevalence of PTD during a 5-year period found in this study ranged from 2.4 to
2.9%, the latter in individuals between 60 and 70 years of age. Women generally
had PTD more often than men. The longitudinal analysis showed that problems with
bad breath (OR = 3.6), blisters (OR = 3.4), burning mouth (OR = 3.4) and self
perceived health (OR = 2.7) were the most important factors explaining PTD.
CONCLUSIONS: This study showed that PTD does not increase between 50 and 70 years
of age in ordinary community-living individuals. There were no long-term impacts
on PTD over time from socio-economic factors, and over time, there were a limited
number of factors contributing to the effect. Bad breath, blisters, burning mouth
and self-perceived health are important factors for the dentist to discuss with
the patient in the case of PTD.
PMID- 27500586
TI - Integrated environmental monitoring and multivariate data analysis-A case study.
AB - The present article describes integration of environmental monitoring and
discharge data and interpretation using multivariate statistics, principal
component analysis (PCA), and partial least squares (PLS) regression. The
monitoring was carried out at the Peregrino oil field off the coast of Brazil.
One sensor platform and 3 sediment traps were placed on the seabed. The sensors
measured current speed and direction, turbidity, temperature, and conductivity.
The sediment trap samples were used to determine suspended particulate matter
that was characterized with respect to a number of chemical parameters (26
alkanes, 16 PAHs, N, C, calcium carbonate, and Ba). Data on discharges of drill
cuttings and water-based drilling fluid were provided on a daily basis. The
monitoring was carried out during 7 campaigns from June 2010 to October 2012,
each lasting 2 to 3 months due to the capacity of the sediment traps. The data
from the campaigns were preprocessed, combined, and interpreted using
multivariate statistics. No systematic difference could be observed between
campaigns or traps despite the fact that the first campaign was carried out
before drilling, and 1 of 3 sediment traps was located in an area not expected to
be influenced by the discharges. There was a strong covariation between suspended
particulate matter and total N and organic C suggesting that the majority of the
sediment samples had a natural and biogenic origin. Furthermore, the multivariate
regression showed no correlation between discharges of drill cuttings and
sediment trap or turbidity data taking current speed and direction into
consideration. Because of this lack of correlation with discharges from the
drilling location, a more detailed evaluation of chemical indicators providing
information about origin was carried out in addition to numerical modeling of
dispersion and deposition. The chemical indicators and the modeling of dispersion
and deposition support the conclusions from the multivariate statistics. Integr
Environ Assess Manag 2017;13:387-395. (c) 2016 SETAC.
PMID- 27500587
TI - Mechanistic variables can enhance predictive models of endotherm distributions:
the American pika under current, past, and future climates.
AB - How climate constrains species' distributions through time and space is an
important question in the context of conservation planning for climate change.
Despite increasing awareness of the need to incorporate mechanism into species
distribution models (SDMs), mechanistic modeling of endotherm distributions
remains limited in this literature. Using the American pika (Ochotona princeps)
as an example, we present a framework whereby mechanism can be incorporated into
endotherm SDMs. Pika distribution has repeatedly been found to be constrained by
warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to
convert macroclimate data to pika-specific surface activity time in summer across
the western United States. We then explored the difference between using a
macroclimate predictor (summer temperature) and using a mechanistic predictor
(predicted surface activity time) in SDMs. Both approaches accurately predicted
pika presences in current and past climate regimes. However, the activity models
predicted 8-19% less habitat loss in response to annual temperature increases of
~3-5 degrees C predicted in the region by 2070, suggesting that pikas may be
able to buffer some climate change effects through behavioral thermoregulation
that can be captured by mechanistic modeling. Incorporating mechanism added value
to the modeling by providing increased confidence in areas where different
modeling approaches agreed and providing a range of outcomes in areas of
disagreement. It also provided a more proximate variable relating animal
distribution to climate, allowing investigations into how unique habitat
characteristics and intraspecific phenotypic variation may allow pikas to exist
in areas outside those predicted by generic SDMs. Only a small number of easily
obtainable data are required to parameterize this mechanistic model for any
endotherm, and its use can improve SDM predictions by explicitly modeling a
widely applicable direct physiological effect: climate-imposed restrictions on
activity. This more complete understanding is necessary to inform climate
adaptation actions, management strategies, and conservation plans.
PMID- 27500588
TI - Development of Nickel Hydrosilylation Catalysts.
AB - In this account, our studies on nickel-catalyzed hydrosilylation reactions are
described. A series of (salicylaldiminato)methylnickel complexes efficiently
catalyze alkene hydrosilylation under ambient reaction conditions. Commercially
available Ni(II) salts, Ni(acac)2 (acac = acetylacetonato) and its derivatives
bis(hexafluoroacetylacetonato)nickel(II) and bis (2,2,6,6-tetramethyl-3,5
heptanedionato)nickel(II), also act as versatile hydrosilylation catalyst
precursors in the presence of NaBHEt3 . These systems catalyze the
hydrosilylation of various alkenes such as industrially important siloxy-, amino
, and epoxy-substituted ones. The arene-supported cationic nickel allyl complexes
also serve as good catalysts for alkene hydrosilylation at room temperature.
These nickel complexes exhibit high selectivity towards the reaction using
secondary hydrosilanes. Mechanistic studies based on experiments and DFT
calculations support a novel mechanism, which includes a facile Si-H bond
cleavage and a Si-C bond formation, assisted by the cooperative action of the
allyl ligand.
PMID- 27500589
TI - Selection for distinct gene expression properties favours the evolution of
mutational robustness in gene regulatory networks.
AB - Mutational robustness is a genotype's tendency to keep a phenotypic trait with
little and few changes in the face of mutations. Mutational robustness is both
ubiquitous and evolutionarily important as it affects in different ways the
probability that new phenotypic variation arises. Understanding the origins of
robustness is specially relevant for systems of development that are
phylogenetically widespread and that construct phenotypic traits with a strong
impact on fitness. Gene regulatory networks are examples of this class of
systems. They comprise sets of genes that, through cross-regulation, build the
gene activity patterns that define cellular responses, different tissues or
distinct cell types. Several empirical observations, such as a greater robustness
of wild-type phenotypes, suggest that stabilizing selection underlies the
evolution of mutational robustness. However, the role of selection in the
evolution of robustness is still under debate. Computer simulations of the
dynamics and evolution of gene regulatory networks have shown that selection for
any gene activity pattern that is steady and self-sustaining is sufficient to
promote the evolution of mutational robustness. Here, I generalize this scenario
using a computational model to show that selection for different aspects of a
gene activity phenotype increases mutational robustness. Mutational robustness
evolves even when selection favours properties that conflict with the
stationarity of a gene activity pattern. The results that I present support an
important role for stabilizing selection in the evolution of robustness in gene
regulatory networks.
PMID- 27500590
TI - Tuning the Rainbow: Systematic Modulation of Donor-Acceptor Systems through Donor
Substituents and Solvent.
AB - A series of donor-acceptor compounds is reported in which the energy of the
triarylamine donor is systematically tuned through para substitution with
electron-donating methoxy and electron-withdrawing cyano groups. The acceptor
units investigated are benzothiadiazole (btd), dipyridophenazine (dppz), and its
[ReCl(CO)3(dppz)] complex. The effect of modulating donor energy on the
electronic and photophysical properties is investigated using (1)H NMR
spectroscopy, DFT calculations, electrochemistry, electronic absorption and
emission spectroscopies, ground state and resonance Raman spectroscopy, and
transient absorption spectroscopy. Qualitative correlations between the donor
energy and the properties of interest are obtained using Hammett sigma(+)
constants. Methoxy and cyano groups are shown to destabilize and stabilize,
respectively, the frontier molecular orbitals, with the HOMO affected more
significantly than the LUMO, narrowing the HOMO-LUMO band gap as the substituent
becomes more electron-donating-observable as a bathochromic shift in low-energy
charge-transfer absorption bands. Charge-transfer emission bands are also
dependent on the electron-donating/withdrawing nature of the substituent, and in
combination with the highly solvatochromic nature of charge-transfer states,
emission can be tuned to span the entire visible region.
PMID- 27500591
TI - Evidence for and Against Genetic Predispositions to Acute and Chronic Altitude
Illnesses.
AB - MacInnis, Martin J., and Michael S. Koehle. Evidence for and against genetic
predispositions to acute and chronic altitude illnesses. High Alt Med Biol.
17:281-293, 2016.-Humans exhibit marked variation in their responses to hypoxia,
with susceptibility to acute and chronic altitude illnesses being a prominent and
medically important example. Many have hypothesized that genetic differences are
the cause of these variable responses to hypoxia; however, until recently, these
hypotheses were based primarily on small (and sometimes anecdotal) reports
pertaining to apparent differences in altitude illness susceptibility between
populations, the notion that a history of altitude illness is indicative of
subsequent risk, the heritability of hypoxia-related traits, and candidate gene
association studies. In the past 5 years, the use of genomic techniques has
helped bolster the claim that susceptibility to some altitude illnesses is likely
the result of genetic variation. For each of the major altitude illnesses, we
summarize and evaluate the evidence stemming from three important characteristics
of a genetic trait: (1) individual susceptibility and repeatability across
assessments, (2) biogeographical differences and familial aggregation, and (3)
association(s) with genetic variants. Evidence to support a genetic basis for
susceptibilities to acute mountain sickness (AMS) and high-altitude cerebral
edema (HACE) is limited, owing partially to the subjective and unclear phenotype
of AMS and the rarity and severity of HACE. In contrast, recent genomic studies
have identified genes that influence susceptibility to high-altitude pulmonary
edema, chronic mountain sickness, and high-altitude pulmonary hypertension. The
collection of more individual, familial, and biogeographical susceptibility data
should improve our understanding of the extent to which genetic variation
contributes to altitude illness susceptibility, and genomic and molecular
investigations have the potential to elucidate the mechanisms that underpin
altitude illness susceptibility.
PMID- 27500593
TI - Improving care planning and coordination for service users with medical co
morbidity transitioning between tertiary medical and primary care services.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Mental health service users with medical co
morbidity frequently experience difficulties accessing and receiving appropriate
treatment in emergency departments. Service users frequently experience
fragmented care planning and coordinating between tertiary medical and primary
care services. Little is known about mental health nurses' perspectives about how
to address these problems. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Emergency
department clinicians' poor communication and negative attitudes have adverse
effects on service users and the quality of care they receive. The findings
contribute to the international evidence about mental health nurses' perspectives
of service users feeling confused and frustrated in this situation, and improving
coordination and continuity of care, facilitating transitions and increasing
family and caregiver participation. Intervention studies are needed to evaluate
if adoption of these measures leads to sustainable improvements in care planning
and coordination, and how service users with medical co-morbidity are treated in
emergency departments in particular. WHAT ARE THE IMPLICATIONS FOR PRACTICE?:
Effective planning and coordination of care are essential to enable smooth
transitions between tertiary medical (emergency departments in particular) and
primary care services for service users with medical co-morbidity. Ongoing
professional development education and support is needed for emergency department
clinicians. There is also a need to develop an organized and systemic approach to
improving service users' experience in emergency departments. ABSTRACT:
Introduction Mental health service users with medical co-morbidity frequently
experience difficulties accessing appropriate treatment in medical hospitals, and
often there is poor collaboration within and between services. Little is known
about mental health nurses' perspectives on how to address these problems. Aim To
explore mental health nurses' perspectives of the experience of service users
with medical co-morbidity in tertiary medical services, and to identify how to
improve care planning and coordination for service users transitioning between
tertiary medical and primary care services. Method Embedded within an experience
based co-design study, focus group discussions were conducted with 17 emergency
department nurses and other clinicians, in Melbourne, Australia. Results Three
main themes were abstracted from the data: feeling confused and frustrated,
enhancing service users' transition and experience and involving families and
caregivers. Participants perceived the service user experience to be
characterized by fear, confusion and a sense of not being listened to. They
highlighted that service users' transition and experience could be enhanced by
facilitating transitions and improving coordination and continuity of care. They
also emphasized the need to increase family and caregiver participation.
Conclusion Our findings contribute to knowledge about improving the way service
users are treated in emergency departments and improving care planning and
coordination; in particular, facilitating transitions, improving coordination and
continuity of care and increasing family and caregiver participation.
PMID- 27500592
TI - Molecular regulation and physiological functions of a novel FaHsfA2c cloned from
tall fescue conferring plant tolerance to heat stress.
AB - Heat stress transcription factors (HSFs) compose a large gene family, and
different members play differential roles in regulating plant responses to
abiotic stress. The objectives of this study were to identify and characterize an
A2-type HSF, FaHsfA2c, in a cool-season perennial grass tall fescue (Festuca
arundinacea Schreb.) for its association with heat tolerance and to determine the
underlying physiological functions and regulatory mechanisms of FaHsfA2c
imparting plant tolerance to heat stress. FaHsfA2c was localized in nucleus and
exhibited a rapid transcriptional increase in leaves and roots during early phase
of heat stress. Ectopic expression of FaHsfA2c improved basal and acquired
thermotolerance in wild-type Arabidopsis and also restored heat-sensitive
deficiency of hsfa2 mutant. Overexpression of FaHsfA2c in tall fescue enhanced
plant tolerance to heat by triggering transcriptional regulation of heat
protective gene expression, improving photosynthetic capacity and maintaining
plant growth under heat stress. Our results indicated that FaHsfA2c acted as a
positive regulator conferring thermotolerance improvement in Arabidopsis and tall
fescue, and it could be potentially used as a candidate gene for genetic
modification and molecular breeding to develop heat-tolerant cool-season grass
species.
PMID- 27500594
TI - Exploring the impact of gender inequities on the promotion of cardiovascular
health of women in Pakistan.
AB - Cardiovascular disease exerts an enormous burden on women's health. The intake of
a healthy diet may reduce this burden. However, social norms and economic
constraints are often factors that restrain women from paying attention to their
diet. Underpinned by critical realism, this study explores how gender/sex
influences decision-making regarding food consumption among women of low
socioeconomic status (SES). The study was carried out at two cardiac facilities
in Karachi, Pakistan, on 24 participants (male and female from different ethnic
backgrounds), who had received health education. Using an interpretive
descriptive approach, the study identified major barriers to a healthy diet:
proscribed gender roles and lack of women's autonomy, power, male domination, and
abusive behaviours. Cardiovascular risk and disease outcomes for the Pakistani
women of low SES are likely to further escalate if individual and structural
barriers are not reduced using multifactorial approaches.
PMID- 27500595
TI - Lower prevalence and greater severity of asthma in hot and dry climate.
AB - OBJECTIVE: To estimate asthma prevalence, severity, and associated factors in
adolescents who live in a low relative humidity environment. METHODS: In this
cross-sectional study, adolescents aged 13-14 years from the city of Petrolina
located in the Brazilian semiarid region answered the International Study of
Asthma and Allergies in Childhood (ISAAC) questionnaire. The possible explanatory
variables of the study were gender, family income, mother's education, smokers in
the household, parental history of asthma, personal history of allergic rhinitis
or atopic dermatitis, and physical activity level. Poisson regression analysis
was used to assess the association between asthma and the explanatory variables.
RESULTS: A total of 1591 adolescents participated in the study, of whom 49.7%
were male. The prevalence of active asthma, severe asthma, and physician
diagnosed asthma were 14.0%, 10.4%, and 17.8%, respectively. Adolescents with
asthma missed more school days than their peers (33 vs. 22 days/year; p<0.03).
Associated factors that remained significant after adjustment were history of
asthma in parents (PR=2.65, p<0.001) and personal diagnosis of allergic rhinitis
(PR=1.96, p<0.001) and/or atopic dermatitis (PR=2.18, p<0.001). CONCLUSION:
Asthma prevalence in this low-humidity environment was lower, but more severe
than those reported in other Brazilian cities. The dry climate might hamper
disease control and this may have contributed to the higher school absenteeism
observed. The association of asthma with allergic rhinitis and atopic dermatitis
as well as a history of asthma in parents suggests that atopy is an important
risk factor for asthma in this population.
PMID- 27500596
TI - Steric and Electronic Effects of Bidentate Phosphine Ligands on Ruthenium(II)
Catalyzed Hydrogenation of Carbon Dioxide.
AB - The reactivity difference between the hydrogenation of CO2 catalyzed by various
ruthenium bidentate phosphine complexes was explored by DFT. In addition to the
ligand dmpe (Me2 PCH2 CH2 PMe2 ), which was studied experimentally previously, a
more bulky diphosphine ligand, dmpp (Me2 PCH2 CH2 CH2 PMe2 ), together with a
more electron-withdrawing diphosphine ligand, PN(Me) P (Me2 PCH2 N(Me) CH2 PMe2
), have been studied theoretically to analyze the steric and electronic effects
on these catalyzed reactions. Results show that all of the most favorable
pathways for the hydrogenation of CO2 catalyzed by bidentate phosphine ruthenium
dihydride complexes undergo three major steps: cis-trans isomerization of
ruthenium dihydride complex, CO2 insertion into the Ru-H bond, and H2 insertion
into the ruthenium formate ion. Of these steps, CO2 insertion into the Ru-H bond
has the lowest barrier compared with the other two steps in each preferred
pathway. For the hydrogenation of CO2 catalyzed by ruthenium complexes of dmpe
and dmpp, cis-trans isomerization of ruthenium dihydride complex has a similar
barrier to that of H2 insertion into the ruthenium formate ion. However, in the
reaction catalyzed by the PN(Me) PRu complex, cis-trans isomerization of the
ruthenium dihydride complex has a lower barrier than H2 insertion into the
ruthenium formate ion. These results suggest that the steric effect caused by the
change of the outer sphere of the diphosphine ligand on the reaction is not
clear, although the electronic effect is significant to cis-trans isomerization
and H2 insertion. This finding refreshes understanding of the mechanism and
provides necessary insights for ligand design in transition-metal-catalyzed CO2
transformation.
PMID- 27500597
TI - Is the Risk of Autism in Younger Siblings of Affected Children Moderated by Sex,
Race/Ethnicity, or Gestational Age?
AB - OBJECTIVE: To evaluate the recurrence risk of autism spectrum disorders (ASD) in
younger siblings of affected children and determine how it is modified by
race/ethnicity and sex. METHOD: Medical records of children born in a large
health maintenance organization (Kaiser Permanent Southern California) hospitals
from January 1, 2001, through December 31, 2010, and who remained in our system
until 2 to 11 years of age were used to assess the risk of recurrence of ASD in
younger siblings. Children born at <28 or >42 weeks gestation, multiple births,
or those who were not active members for >=3 months were excluded. ASD diagnosis
was ascertained from DSM-IV codes, and the magnitude of the association was
estimated using adjusted relative risks (aRRs). RESULTS: Among eligible younger
siblings, 592 (1.11%) had the diagnosis of ASD. The ASD rates were 11.30% and
0.92% for younger siblings of older affected and unaffected siblings,
respectively (aRR: 14.27; 95% confidence interval, 11.41-17.83). This association
remained after adjusting for potential confounding factors. Race/ethnicity- and
gestational age-specific analyses revealed a positive association of similar
magnitude across groups. Risk remained higher in younger boys than girls
regardless of the sex of affected older siblings. CONCLUSION: The findings of
this study suggest that the risk of ASD in younger siblings is higher if the
older sibling has ASD. The risk of ASD in younger siblings of older affected
siblings was comparable across gestational age at birth and child's
race/ethnicity groups. However, risk remains higher for boys. This study
contributes to a better understanding of the influence of race/ethnicity, sex,
and gestational age at birth in identifying children at higher risk of ASD.
PMID- 27500598
TI - Metal-Free Oxidative Radical Alkynylation/Ring Expansion Rearrangement of Alkenyl
Cyclobutanols with Ethynylbenziodoxolones.
AB - The first metal-free alkynylation/ring expansion cascade process of alkenyl
cyclobutanols with ethynylbenziodoxolones has been developed. A variety of
synthetically valuable beta-alkynylated cyclopentanones were prepared in moderate
to good yields. Alkynyl cyclobutanols could also undergo this transformation,
providing a new approach to substituted ene-yne-carbonyl compounds.
PMID- 27500599
TI - Regional Intestinal Permeability in Dogs: Biopharmaceutical Aspects for
Development of Oral Modified-Release Dosage Forms.
AB - The development of oral modified-release (MR) dosage forms requires an active
pharmaceutical ingredient (API) with a sufficiently high absorption rate in both
the small and large intestine. Dogs are commonly used in preclinical evaluation
of regional intestinal absorption and in the development of novel MR dosage
forms. This study determined regional intestinal effective permeability (Peff) in
dogs with the aim to improve regional Peff prediction in humans. Four model
drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and
regionally dosed twice as a solution into the proximal small intestine (P-SI) and
large intestine (LI) of three dogs with intestinal stomas. Based on plasma data
from two separate study occasions for each dog, regional Peff values were
calculated using a validated intestinal deconvolution method. The determined mean
Peff values were 0.62, 0.14, 1.06, and 3.66 * 10(-4) cm/s in the P-SI, and 0.13,
0.02, 1.03, and 2.20 * 10(-4) cm/s in the LI, for atenolol, enalaprilat,
metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog
were highly correlated (R(2) = 0.98) to the historically directly determined
human jejunal Peff after a single-pass perfusion. The determined dog P-SI Peff
values were also successfully implemented in GI-Sim to predict the risk for
overestimation of LI absorption of low permeability drugs. We conclude that the
dog intestinal stoma model is a useful preclinical tool for determination of
regional intestinal permeability. Still, further studies are recommended to
evaluate additional APIs, sources of variability, and formulation types, for more
accurate determination of the dog model in the drug development process.
PMID- 27500600
TI - Placental perfusion: interest and limits.
PMID- 27500601
TI - Chemoenzymatic Synthesis and Receptor Binding of Mannose-6-Phosphate (M6P)
Containing Glycoprotein Ligands Reveal Unusual Structural Requirements for M6P
Receptor Recognition.
AB - Mannose-6-phosphate (M6P)-terminated oligosaccharides are important signals for
M6P-receptor-mediated targeting of newly synthesized hydrolases from Golgi to
lysosomes, but the precise structural requirement for the M6P ligand-receptor
recognition has not been fully understood due to the difficulties in obtaining
homogeneous M6P-containing glycoproteins. We describe here a chemoenzymatic
synthesis of homogeneous phosphoglycoproteins carrying natural M6P-containing N
glycans. The method includes the chemical synthesis of glycan oxazolines with
varied number and location of the M6P moieties and their transfer to the GlcNAc
protein by an endoglycosynthase to provide homogeneous M6P-containing
glycoproteins. Simultaneous attachment of two M6P-oligosaccahrides to a cyclic
polypeptide was also accomplished to yield bivalent M6P-glycopeptides. Surface
plasmon resonance binding studies reveal that a single M6P moiety located at the
low alpha-1,3-branch of the oligomannose context is sufficient for a high
affinity binding to receptor CI-MPR, while the presence of a M6P moiety at the
alpha-1,6-branch is dispensable. In addition, a binding study with the bivalent
cyclic and linear polypeptides reveals that a close proximity of two M6P
oligosaccharide ligands is critical to achieve high affinity for the CI-MPR
receptor. Taken together, the present study indicates that the location and
valency of the M6P moieties and the right oligosaccharide context are all
critical for high-affinity binding with the major M6P receptor. The
chemoenzymatic method described here provides a new avenue for glycosylation
remodeling of recombinant enzymes to enhance the uptake and delivery of enzymes
to lysosomes in enzyme replacement therapy for the treatment of lysosomal storage
diseases.
PMID- 27500602
TI - Conscious and Non-conscious Representations of Emotional Faces in Asperger's
Syndrome.
AB - Several neuroimaging studies have suggested that the low spatial frequency
content in an emotional face mainly activates the amygdala, pulvinar, and
superior colliculus especially with fearful faces(1-3). These regions constitute
the limbic structure in non-conscious perception of emotions and modulate
cortical activity either directly or indirectly(2). In contrast, the conscious
representation of emotions is more pronounced in the anterior cingulate,
prefrontal cortex, and somatosensory cortex for directing voluntary attention to
details in faces(3,4). Asperger's syndrome (AS)(5,6) represents an atypical
mental disturbance that affects sensory, affective and communicative abilities,
without interfering with normal linguistic skills and intellectual ability.
Several studies have found that functional deficits in the neural circuitry
important for facial emotion recognition can partly explain social communication
failure in patients with AS(7-9). In order to clarify the interplay between
conscious and non-conscious representations of emotional faces in AS, an EEG
experimental protocol is designed with two tasks involving emotionality
evaluation of either photograph or line-drawing faces. A pilot study is
introduced for selecting face stimuli that minimize the differences in reaction
times and scores assigned to facial emotions between the pretested patients with
AS and IQ/gender-matched healthy controls. Information from the pretested
patients was used to develop the scoring system used for the emotionality
evaluation. Research into facial emotions and visual stimuli with different
spatial frequency contents has reached discrepant findings depending on the
demographic characteristics of participants and task demands(2). The experimental
protocol is intended to clarify deficits in patients with AS in processing
emotional faces when compared with healthy controls by controlling for factors
unrelated to recognition of facial emotions, such as task difficulty, IQ and
gender.
PMID- 27500605
TI - No silver bullet: different soil handling techniques are useful for different
research questions, exhibit differential type I and II error rates, and are
sensitive to sampling intensity.
PMID- 27500603
TI - Continuous Glucose Monitor Use and Accuracy in Hospitalized Patients.
PMID- 27500604
TI - Evaluation of the Impact of Methicillin-Resistant Staphylococcus pseudintermedius
Biofilm Formation on Antimicrobial Susceptibility.
AB - OBJECTIVE: To compare the minimum inhibitory concentration (MIC) of four
antimicrobials in planktonic vs. biofilm-associated Staphylococcus
pseudintermedius. STUDY DESIGN: In vitro study. SAMPLE POPULATION: 78 isolates
from dogs colonized or infected with methicillin-resistant S. pseudintermedius
(MRSP, n=39) or methicillin-susceptible S. pseudintermedius (MSSP, n=39).
METHODS: Agar dilution was used to determine the MIC of amikacin, cefazolin,
enrofloxacin, and gentamicin for planktonic bacteria. A modified broth
microdilution assay was used to assess the MIC of biofilm-associated bacteria.
RESULTS: MIC were significantly higher in biofilm-associated vs. planktonic
bacteria for all antimicrobials; amikacin (median MIC: biofilm >2,000 MUg/mL vs.
planktonic 3 MUg/mL, P<.0001), cefazolin (>1,000 vs. 0.5 MUg/mL, P<.0001),
enrofloxacin (>1,000 vs. 0.25 MUg/mL, P<.0001), and gentamicin (>1,000 vs. 0.3
MUg/mL, P<.001). For all antimicrobials, there were significant differences in
planktonic MIC for MRSP and MSSP (all P<.0001) but no differences between biofilm
MIC for MRSP and MSSP (P=.08-1.0). CONCLUSION: The MIC for biofilm-associated S.
pseudintermedius are significantly higher than for planktonic bacteria. Standard
methods for determining MIC are not appropriate for biofilm-associated
infections. This must be considered when determining treatment regimens for
infections that potentially involve biofilms, and further study of methods to
control biofilm-associated infections is needed.
PMID- 27500606
TI - Vascular Malformations and Associated Syndromes: The Role of the Orthopaedic
Surgeon.
PMID- 27500607
TI - Management of Osteoporotic Patients with Distal Radial Fractures.
PMID- 27500608
TI - Hip Resection Arthroplasty.
PMID- 27500609
TI - Cervical Traction for the Treatment of Spinal Injury and Deformity.
PMID- 27500611
TI - Pediatric Critical Care Medicine: Accomplishments and Important New Initiatives.
PMID- 27500610
TI - Visualization of HIV-1 Gag Binding to Giant Unilamellar Vesicle (GUV) Membranes.
AB - The structural protein of HIV-1, Pr55(Gag) (or Gag), binds to the plasma membrane
in cells during the virus assembly process. Membrane binding of Gag is an
essential step for virus particle formation, since a defect in Gag membrane
binding results in severe impairment of viral particle production. To gain
mechanistic details of Gag-lipid membrane interactions, in vitro methods based on
NMR, protein footprinting, surface plasmon resonance, liposome flotation
centrifugation, or fluorescence lipid bead binding have been developed thus far.
However, each of these in vitro methods has its limitations. To overcome some of
these limitations and provide a complementary approach to the previously
established methods, we developed an in vitro assay in which interactions between
HIV-1 Gag and lipid membranes take place in a "cell-like" environment. In this
assay, Gag binding to lipid membranes is visually analyzed using YFP-tagged Gag
synthesized in a wheat germ-based in vitro translation system and GUVs prepared
by an electroformation technique. Here we describe the background and the
protocols to obtain myristoylated full-length Gag proteins and GUV membranes
necessary for the assay and to detect Gag-GUV binding by microscopy.
PMID- 27500612
TI - Multisite Tissue Oxygenation Monitoring Indicates Organ-Specific Flow
Distribution and Oxygen Delivery Related to Low Cardiac Output in Preterm Infants
With Clinical Sepsis.
AB - OBJECTIVES: Cardiac output may be compromised in preterm infants with sepsis.
Whether low cardiac output is associated with low tissue oxygen supply in these
patients is unclear. The aim of the current study was to assess the association
between cardiac output, assessed by echocardiography, and tissue oxygenation,
measured with multisite near-infrared spectroscopy, in a cohort of preterm
infants with clinical sepsis. DESIGN: Prospective observational cohort study.
SETTING: Level III neonatal ICU. PATIENTS: Twenty-four preterm infants
(gestational age < 32 wk) with clinical sepsis. INTERVENTIONS: None. MEASUREMENTS
AND MAIN RESULTS: Clinical and echocardiographic assessment of hemodynamics was
performed within 48 hours of sepsis workup and repeated at least 24 hours later.
We measured cerebral, renal, and intestinal tissue oxygen saturation using near
infrared spectroscopy during an hour of stable measurements directly preceding or
following echocardiography and calculated fractional tissue oxygen extraction in
each tissue. We determined Spearman correlation coefficients between fractional
tissue oxygen extraction and right ventricular output corrected for patent
foramen ovale flow, left ventricular output corrected for ductus arteriosus flow,
and superior vena cava flow. Right ventricular output corrected for patent
foramen ovale and left ventricular output corrected for ductus arteriosus flow
both correlated significantly with intestinal fractional tissue oxygen extraction
(rho, -0.700; p = 0.036 and rho, -0.604; p = 0.029, respectively). In contrast,
no significant correlations were found between cardiac output measurements and
cerebral and renal fractional tissue oxygen extraction, respectively. Changes in
cardiac output measurements were not associated with observed changes in
fractional tissue oxygen extraction values. CONCLUSIONS: Right ventricular output
corrected for patent foramen ovale and left ventricular output corrected for
ductus arteriosus flow, indicators of systemic blood flow in preterm infants with
shunts, were negatively associated with intestinal fractional tissue oxygen
extraction, but not with renal and cerebral fractional tissue oxygen extraction.
These findings suggest that during low output states due to clinical sepsis
intestinal perfusion is most at risk.
PMID- 27500613
TI - Targeted Temperature Management After Cardiac Arrest Due to Drowning:
"Frequentist" and "Bayesian" Decision Making.
PMID- 27500614
TI - How to Sustain Quality Improvements in Sedation Practice?
PMID- 27500615
TI - Sepsis: From the Stone Age to Nowadays Without a Precise Definition.
PMID- 27500616
TI - Critical Pertussis Among Infants-Many More Miles to Go!
PMID- 27500617
TI - You Can Teach an Old Drug New Tricks-Aminophylline for Cardiac Surgery-Associated
Acute Kidney Injury.
PMID- 27500618
TI - Lies, Statistics, and ECMO Data Mining: Digging Dirt or Striking Gold?
PMID- 27500619
TI - Tracheostomies and Long-Term Ventilation in Children: Are We Being Thoughtful and
Consistent?
PMID- 27500620
TI - Increasing Access to the Benefits of Palliative Care in the PICU.
PMID- 27500621
TI - Lower Respiratory Tract Infections: Risks Are High in Early Childhood.
PMID- 27500622
TI - Pediatric Acute Kidney Injury: The Fight of Inadequate Education Versus
Inadequate Literature.
PMID- 27500623
TI - Patient-Ventilator Asynchrony During Assisted Ventilation in Children: The Time
to Rethink Our Knowledge.
PMID- 27500624
TI - The authors reply.
PMID- 27500625
TI - Strain Echocardiography in Pediatric Sepsis: Direct Guide to Hemodynamic Therapy
in the Future?
PMID- 27500626
TI - The authors reply.
PMID- 27500627
TI - Use of Aminophylline to Prevent Acute Kidney Injury After Pediatric Cardiac
Surgery.
PMID- 27500628
TI - The authors reply.
PMID- 27500629
TI - The Current State of the Diagnosis and Management of Acute Kidney Injury by
Pediatric Critical Care Physicians.
AB - OBJECTIVES: Increasingly prevalent in pediatric intensive care, acute kidney
injury imparts significant short- and long-term consequences. Despite advances in
acute kidney injury research, clinical outcomes are worsening. We surveyed
pediatric critical care physicians to describe the current state of acute kidney
injury diagnosis and management in critically ill children. DESIGN: Anonymous
electronic questionnaire. PARTICIPANTS: Pediatric critical care physicians from
academic centers, the Pediatric Acute Lung Injury and Sepsis Investigators
network, and/or the pediatric branch of Society of Critical Care Medicine.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 201 surveys initiated, 170
surveys were more than 50% completed and included in our results. The majority of
physicians (74%) diagnosed acute kidney injury using serum creatinine and urine
output. Acute kidney injury guidelines or criteria were used routinely by 54% of
physicians; Risk, Injury, Failure, Loss, and End stage criteria were the most
commonly used. Awareness of any acute kidney injury guideline or definition was
associated with five-fold higher odds of using any guideline (odds ratio, 5.22;
95% CI, 1.84-14.83) and four-fold higher odds of being dissatisfied with
available acute kidney injury biomarkers (odds ratio, 4.88; 95% CI, 1.58-15.05).
Less than half of respondents recognized the limitations of serum creatinine.
Physicians unaware of the limitations of serum creatinine had two-fold higher
odds of being unaware of newer biomarker availability (odds ratio, 2.34; 95% CI,
1.14-4.79). Novel biomarkers were available to 37.6% of physicians for routine
use. Physicians with access to novel biomarkers more often practiced in larger
(odds ratio, 3.09; 95% CI, 1.18-8.12) and Midwestern (odds ratio, 3.38; 95% CI,
1.47-7.78) institutions. More physicians with access to a novel biomarker
reported satisfaction with current acute kidney injury diagnostics (66%) than
physicians without access (48%); this finding approached significance (p = 0.07).
CONCLUSIONS: Half of PICU attending physicians surveyed are not using recent
acute kidney injury guidelines or diagnostic criteria in their practice. There is
a positive association between awareness and clinical use of acute kidney injury
guidelines. Serum creatinine and urine output are still the primary diagnostics;
novel biomarkers are frequently unavailable.
PMID- 27500630
TI - A Novel Behavioral Assay to Investigate Gustatory Responses of Individual, Freely
moving Bumble Bees (Bombus terrestris).
AB - Generalist pollinators like the buff-tailed bumble bee, Bombus terrestris,
encounter both nutrients and toxins in the floral nectar they collect from
flowering plants. Only a few studies have described the gustatory responses of
bees toward toxins in food, and these experiments have mainly used the proboscis
extension response on restrained honey bees. Here, a new behavioral assay is
presented for measuring the feeding responses of freely-moving, individual worker
bumble bees to nutrients and toxins. This assay measures the amount of solution
ingested by each bumble bee and identifies how tastants in food influence the
microstructure of the feeding behavior. The solutions are presented in a
microcapillary tube to individual bumble bees that have been previously starved
for 2-4 hr. The behavior is captured on digital video. The fine structure of the
feeding behavior is analyzed by continuously scoring the position of the
proboscis (mouthparts) from video recordings using event logging software. The
position of the proboscis is defined by three different behavioral categories:
(1) proboscis is extended and in contact with the solution, (2) proboscis is
extended but not in contact with the solution and (3) proboscis is stowed under
the head. Furthermore the speed of the proboscis retracting away from the
solution is also estimated. In the present assay the volume of solution consumed,
the number of feeding bouts, the duration of the feeding bouts and the speed of
the proboscis retraction after the first contact is used to evaluate the
phagostimulatory or the deterrent activity of the compounds tested. This new
taste assay will allow researchers to measure how compounds found in nectar
influence the feeding behavior of bees and will also be useful to pollination
biologists, toxicologists and neuroethologists studying the bumble bee's taste
system.
PMID- 27500632
TI - The challenge of treating elderly coronary artery disease patients.
PMID- 27500631
TI - Plasma cell differentiation is coupled to division-dependent DNA hypomethylation
and gene regulation.
AB - The epigenetic processes that regulate antibody-secreting plasma cells are not
well understood. Here, analysis of plasma cell differentiation revealed DNA
hypomethylation of 10% of CpG loci that were overrepresented at enhancers.
Inhibition of DNA methylation enhanced plasma cell commitment in a cell-division
dependent manner. Analysis of B cells differentiating in vivo stratified by cell
division revealed a fivefold increase in mRNA transcription coupled to DNA
hypomethylation. Demethylation occurred first at binding motifs for the
transcription factors NF-kappaB and AP-1 and later at those for the transcription
factors IRF and Oct-2 and was coincident with activation and differentiation gene
expression programs in a cell-division-dependent manner. These data provide
mechanistic insight into cell-division-coupled transcriptional and epigenetic
reprogramming and suggest that DNA hypomethylation reflects the cis-regulatory
history of plasma cell differentiation.
PMID- 27500633
TI - Are Epiphytic Microbial Communities in the Carposphere of Ripening Grape Clusters
(Vitis vinifera L.) Different between Conventional, Organic, and Biodynamic
Grapes?
AB - Using barcoded pyrosequencing fungal and bacterial communities associated with
grape berry clusters (Vitis vinifera L.) obtained from conventional, organic and
biodynamic vineyard plots were investigated in two subsequent years at different
stages during berry ripening. The four most abundant operational taxonomic units
(OTUs) based on fungal ITS data were Botrytis cinerea, Cladosporium spp.,
Aureobasidium pullulans and Alternaria alternata which represented 57% and 47% of
the total reads in 2010 and 2011, respectively. Members of the genera
Sphingomonas, Gluconobacter, Pseudomonas, Erwinia, and Massilia constituted 67%
of the total number of bacterial 16S DNA reads in 2010 samples and 78% in 2011
samples. Viticultural management system had no significant effect on abundance of
fungi or bacteria in both years and at all three sampling dates. Exceptions were
A. alternata and Pseudomonas spp. which were more abundant in the carposphere of
conventional compared to biodynamic berries, as well as Sphingomonas spp. which
was significantly less abundant on conventional compared to organic berries at an
early ripening stage in 2011. In general, there were no significant differences
in fungal and bacterial diversity indices or richness evident between management
systems. No distinct fungal or bacterial communities were associated with the
different maturation stages or management systems, respectively. An exception was
the last stage of berry maturation in 2011, where the Simpson diversity index was
significantly higher for fungal communities on biodynamic compared to
conventional grapes. Our study highlights the existence of complex and dynamic
microbial communities in the grape cluster carposphere including both
phytopathogenic and potentially antagonistic microorganisms that can have a
significant impact on grape production. Such knowledge is particularly relevant
for development, selection and application of effective control measures against
economically important pathogens present in the grape carposphere.
PMID- 27500634
TI - Hybridization between nanocavities for a polarimetric color sorter at the sub
micron scale.
AB - Metallic hole arrays have been recently used for color generation and filtering
due to their reliability and color tunability. However, color generation is still
limited to several microns. Understanding the interaction between the individual
elements of the whole nanostructure may push the resolution to the sub-micron
level. Herein, we study the hybridization between silver nanocavities in order to
obtain active color generation at the micron scale. To do so, we use five
identical triangular cavities which are separated by hundreds of nanometers from
each other. By tuning either the distance between the cavities or the optical
polarization state of the incoming field, the transmitted light through the
cavities is actively enhanced at specific frequencies. Consequently, a rainbow of
colors is observed from a sub-micron scale unit. The reason for this is that the
metallic surface plays a vital role in the hybridization between the cavities and
contributes to higher frequency modes. Cathodoluminescence measurements have
confirmed this assumption and have revealed that these five triangular cavities
act as a unified entity surrounded by the propagated surface plasmons. In such
plasmonic structures, multi-color tuning can be accomplished and may open the
possibility to improve color generation and high-quality pixel fabrication.
PMID- 27500635
TI - Quantitation of Intra-peritoneal Ovarian Cancer Metastasis.
AB - Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic
malignancy in the United States. Mortality is due to diagnosis of 75% of women
with late stage disease, when metastasis is already present. EOC is characterized
by diffuse and widely disseminated intra-peritoneal metastasis. Cells shed from
the primary tumor anchor in the mesothelium that lines the peritoneal cavity as
well as in the omentum, resulting in multi-focal metastasis, often in the
presence of peritoneal ascites. Efforts in our laboratory are directed at a more
detailed understanding of factors that regulate EOC metastatic success. However,
quantifying metastatic tumor burden represents a significant technical challenge
due to the large number, small size and broad distribution of lesions throughout
the peritoneum. Herein we describe a method for analysis of EOC metastasis using
cells labeled with red fluorescent protein (RFP) coupled with in vivo
multispectral imaging. Following intra-peritoneal injection of RFP-labelled tumor
cells, mice are imaged weekly until time of sacrifice. At this time, the
peritoneal cavity is surgically exposed and organs are imaged in situ. Dissected
organs are then placed on a labeled transparent template and imaged ex vivo.
Removal of tissue auto-fluorescence during image processing using multispectral
unmixing enables accurate quantitation of relative tumor burden. This method has
utility in a variety of applications including therapeutic studies to evaluate
compounds that may inhibit metastasis and thereby improve overall survival.
PMID- 27500636
TI - Virtual Hematoxylin and Eosin Transillumination Microscopy Using Epi-Fluorescence
Imaging.
AB - We derive a physically realistic model for the generation of virtual
transillumination, white light microscopy images using epi-fluorescence
measurements from thick, unsectioned tissue. We demonstrate this technique by
generating virtual transillumination H&E images of unsectioned human breast
tissue from epi-fluorescence multiphoton microscopy data. The virtual
transillumination algorithm is shown to enable improved contrast and color
accuracy compared with previous color mapping methods. Finally, we present an
open source implementation of the algorithm in OpenGL, enabling real-time GPU
based generation of virtual transillumination microscopy images using
conventional fluorescence microscopy systems.
PMID- 27500637
TI - Structural and functional basis of phospholipid oxygenase activity of bacterial
lipoxygenase from Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa expresses a secreted LOX-isoform (PA-LOX, LoxA) capable of
oxidizing polyenoic fatty acids to hydroperoxy derivatives. Here we report high
level expression of this enzyme in E. coli and its structural and functional
characterization. Recombinant PA-LOX oxygenates polyenoic fatty acids including
eicosapentaenoic acid and docosahexaenoic acid to the corresponding (n-6)S
hydroperoxy derivatives. This reaction involves abstraction of the proS-hydrogen
from the n-8 bisallylic methylene. PA-LOX lacks major leukotriene synthase
activity but converts 5S-HETE and 5S,6R/S-DiHETE to anti-inflammatory and pro
resolving lipoxins. It also exhibits phospholipid oxygenase activity as indicated
by the formation of a specific pattern of oxygenation products from different
phospholipid subspecies. Multiple mutagenesis studies revealed that PA-LOX does
not follow classical concepts explaining the reaction specificity of mammalian
LOXs. The crystal structure of PA-LOX was solved with resolutions of up to 1.48A
and its polypeptide chain is folded as single domain. The substrate-binding
pocket consists of two fatty acid binding subcavities and lobby. Subcavity-1
contains the catalytic non-heme iron. A phosphatidylethanolamine molecule
occupies the substrate-binding pocket and its sn1 fatty acid is located close to
the catalytic non-heme iron. His377, His382, His555, Asn559 and the C-terminal
Ile685 function as direct iron ligands and a water molecule (hydroxyl) completes
the octahedral ligand sphere. Although the biological relevance of PA-LOX is
still unknown its functional characteristics (lipoxin synthase activity)
implicate this enzyme in a bacterial evasion strategy aimed at downregulating the
hosts' immune system.
PMID- 27500638
TI - Yeast Biodiversity in Vineyard Environments Is Increased by Human Intervention.
AB - One hundred and five grape samples were collected during two consecutive years
from 33 locations on seven oceanic islands of the Azores Archipelago. Grape
samples were obtained from vineyards that were either abandoned or under regular
cultivation involving common viticultural interventions, to evaluate the impact
of regular human intervention on grape yeast biota diversity in vineyards. A
total of 3150 yeast isolates were obtained and 23 yeast species were identified.
The predominant species were Hanseniaspora uvarum, Pichia terricola, Starmerella
bacillaris and Issatchenkia hanoiensis. The species Barnettozyma californica,
Candida azymoides and Pichia cecembensis were reported in grapes or wine
associated environments for the first time. A higher biodiversity was found in
active vineyards where regular human intervention takes place (Shannon index:
1.89 and 1.53 in the first and second years, respectively) when compared to the
abandoned ones (Shannon index: 0.76 and 0.31). This finding goes against the
assumptions that human intervention can destroy biodiversity and lead to
homogeneity in the environment. Biodiversity indices were considerably lower in
the year with the heaviest rainfall. This study is the first to report on the
grape yeast communities from several abandoned vineyards that have undergone no
human intervention.
PMID- 27500640
TI - Multiclass Classification for the Differential Diagnosis on the ADHD Subtypes
Using Recursive Feature Elimination and Hierarchical Extreme Learning Machine:
Structural MRI Study.
AB - The classification of neuroimaging data for the diagnosis of certain brain
diseases is one of the main research goals of the neuroscience and clinical
communities. In this study, we performed multiclass classification using a
hierarchical extreme learning machine (H-ELM) classifier. We compared the
performance of this classifier with that of a support vector machine (SVM) and
basic extreme learning machine (ELM) for cortical MRI data from attention
deficit/hyperactivity disorder (ADHD) patients. We used 159 structural MRI images
of children from the publicly available ADHD-200 MRI dataset. The data consisted
of three types, namely, typically developing (TDC), ADHD-inattentive (ADHD-I),
and ADHD-combined (ADHD-C). We carried out feature selection by using standard
SVM-based recursive feature elimination (RFE-SVM) that enabled us to achieve good
classification accuracy (60.78%). In this study, we found the RFE-SVM feature
selection approach in combination with H-ELM to effectively enable the
acquisition of high multiclass classification accuracy rates for structural
neuroimaging data. In addition, we found that the most important features for
classification were the surface area of the superior frontal lobe, and the
cortical thickness, volume, and mean surface area of the whole cortex.
PMID- 27500639
TI - HIV-1-Specific Antibody Response and Function after DNA Prime and Recombinant
Adenovirus 5 Boost HIV Vaccine in HIV-Infected Subjects.
AB - Little is known about the humoral immune response against DNA prime-recombinant
adenovirus 5 (rAd5) boost HIV vaccine among HIV-infected patients on long-term
suppressive antiretroviral therapy (ART). Previous studies emphasized cellular
immune responses; however, current research suggests both cellular and humoral
responses are likely required for a successful therapeutic vaccine. Thus, we
aimed to understand antibody response and function induced by vaccination of ART
treated HIV-1-infected patients with immune recovery. All subjects participated
in EraMune 02, an open-label randomized clinical trial of ART intensification
followed by a six plasmid DNA prime (envA, envB, envC, gagB, polB, nefB) and rAd5
boost HIV vaccine with matching inserts. Antibody binding levels were determined
with a recently developed microarray approach. We also analyzed neutralization
efficiency and antibody-dependent cellular cytotoxicity (ADCC). We found that the
DNA prime-rAd5 boost vaccine induced a significant cross-clade HIV-specific
antibody response, which correlated with antibody neutralization efficiency.
However, despite the increase in antibody binding levels, the vaccine did not
significantly stimulate neutralization or ADCC responses. This finding was also
reflected by a lack of change in total CD4+ cell associated HIV DNA in those who
received the vaccine. Our results have important implications for further
therapeutic vaccine design and administration, especially in HIV-1 infected
patients, as boosting of preexisting antibody responses are unlikely to lead to
clearance of latent proviruses in the HIV reservoir.
PMID- 27500642
TI - Simultaneous qualitative and quantitative analysis of 21 mycotoxins in Radix
Paeoniae Alba by ultra-high performance liquid chromatography quadrupole linear
ion trap mass spectrometry and QuEChERS for sample preparation.
AB - A high-throughput method for simultaneous qualitative and quantitative analysis
of 21 mycotoxins in Radix Paeoniae Alba (RPA) was developed by coupling the
modified QuEChERS method with ultra-high performance liquid chromatography
quadrupole linear ion trap mass spectrometry (UHPLC-QqLIT-MS). The 21 mycotoxins
were extracted and cleaned up using QuEChERS-based procedure, then further
separated on a C18 column and detected by a hybrid triple quadrupole linear ion
trap mass spectrometer equipped with electrospray ionization source in the
multiple reaction monitoring-information dependent acquisition-enhanced product
ion (MRM-IDA-EPI) mode. Under this technique, 13 mycotoxins were detected using
acetonitrile and water containing 0.1% formic acid as the mobile phase in
positive mode while the other 8 mycotoxins were detected using acetonitrile and
water containing 0.1% ammonia as the mobile phase in negative mode. The
calibration curves of all analytes showed good linearity (r(2)>0.995) within test
ranges. The limits of detection and quantification ranged from 0.031 to 5.4MUg/kg
and 0.20 to 22MUg/kg, respectively. Additionally, recoveries were all above 75.3%
with relative standard deviations within 15%. The method proposed herein with
significant advantages including simple pretreatment, rapid determination as well
as high sensitivity, accuracy and throughput would be a preferred candidate for
the determination and quantification of multi-class mycotoxin contaminants in
real samples.
PMID- 27500641
TI - Potent Allosteric Dengue Virus NS5 Polymerase Inhibitors: Mechanism of Action and
Resistance Profiling.
AB - Flaviviruses comprise major emerging pathogens such as dengue virus (DENV) or
Zika virus (ZIKV). The flavivirus RNA genome is replicated by the RNA-dependent
RNA polymerase (RdRp) domain of non-structural protein 5 (NS5). This essential
enzymatic activity renders the RdRp attractive for antiviral therapy. NS5
synthesizes viral RNA via a "de novo" initiation mechanism. Crystal structures of
the flavivirus RdRp revealed a "closed" conformation reminiscent of a pre
initiation state, with a well ordered priming loop that extrudes from the thumb
subdomain into the dsRNA exit tunnel, close to the "GDD" active site. To-date, no
allosteric pockets have been identified for the RdRp, and compound screening
campaigns did not yield suitable drug candidates. Using fragment-based screening
via X-ray crystallography, we found a fragment that bound to a pocket of the apo
DENV RdRp close to its active site (termed "N pocket"). Structure-guided
improvements yielded DENV pan-serotype inhibitors of the RdRp de novo initiation
activity with nano-molar potency that also impeded elongation activity at micro
molar concentrations. Inhibitors exhibited mixed inhibition kinetics with respect
to competition with the RNA or GTP substrate. The best compounds have EC50 values
of 1-2 MUM against all four DENV serotypes in cell culture assays. Genome
sequencing of compound-resistant DENV replicons, identified amino acid changes
that mapped to the N pocket. Since inhibitors bind at the thumb/palm interface of
the RdRp, this class of compounds is proposed to hinder RdRp conformational
changes during its transition from initiation to elongation. This is the first
report of a class of pan-serotype and cell-active DENV RdRp inhibitors. Given the
evolutionary conservation of residues lining the N pocket, these molecules offer
insights to treat other serious conditions caused by flaviviruses.
PMID- 27500643
TI - Development of a Monoclonal Antibody Against Porcine Circovirus2 Cap Protein.
AB - Female BALB/c mice were immunized with a commercial PCV2 vaccine, and a
monoclonal antibody (MAb) designated as 3H11 was achieved by hybridoma
techniques. The MAb specifically reacted with Cap protein of PCV2, which has been
identified by western blot. Immunoperoxidase monolayer assay results showed that
3H11 did not cross-react with PCV1-infected cells. Therefore, this work suggested
that 3H11 could be a useful tool as a specific diagnostic reagent for PCV2
research.
PMID- 27500644
TI - Activating Receptor Signals Drive Receptor Diversity in Developing Natural Killer
Cells.
AB - It has recently been appreciated that NK cells exhibit many features reminiscent
of adaptive immune cells. Considerable heterogeneity exists with respect to the
ligand specificity of individual NK cells and as such, a subset of NK cells can
respond, expand, and differentiate into memory-like cells in a ligand-specific
manner. MHC I-binding inhibitory receptors, including those belonging to the Ly49
and KIR families, are expressed in a variegated manner, which creates ligand
specific diversity within the NK cell pool. However, how NK cells determine which
inhibitory receptors to express on their cell surface during a narrow window of
development is largely unknown. In this manuscript, we demonstrate that signals
from activating receptors are critical for induction of Ly49 and KIR receptors
during NK cell development; activating receptor-derived signals increased the
probability of the Ly49 bidirectional Pro1 promoter to transcribe in the forward
versus the reverse direction, leading to stable expression of Ly49 receptors in
mature NK cells. Our data support a model where the balance of activating and
inhibitory receptor signaling in NK cells selects for the induction of
appropriate inhibitory receptors during development, which NK cells use to create
a diverse pool of ligand-specific NK cells.
PMID- 27500645
TI - Sex steroid-induced DNA methylation changes and inflammation response in prostate
cancer.
AB - BACKGROUND: Sex steroid hormones have been reported to induce inflammation
causing dysregulation of cytokines in prostate cancer cells. However, the
underlying epigenetic mechanism has not well been studied. The objective of this
study was to evaluate the effect of sex steroid hormones on epigenetic DNA
methylation changes in prostate cancer cells using a signature PCR methylation
array panel that correspond to 96 genes with biological function in the human
inflammatory and autoimmune signals in prostate cancer. Of the 96-gene panel, 32
genes showed at least 10% differentially methylation level in response to
hormonal treatment when compared to untreated cells. Genes that were
hypomethylated included CXCL12, CXCL5, CCL25, IL1F8, IL13RAI, STAT5A, CXCR4 and
TLR5; and genes that were hypermethylated included ELA2, TOLLIP, LAG3, CD276 and
MALT1. Quantitative RT-PCR analysis of select genes represented in a cytokine
expression array panel showed inverse association between DNA methylation and
gene expression for TOLLIP, CXCL5, CCL18 and IL5 genes and treatment of prostate
cancer cells with 5'-aza-2'-deoxycytidine with or without trichostatin A induced
up-regulation of TOLLIP expression. Further analysis of relative gene expression
of matched prostate cancer tissues when compared to benign tissues from
individual patients with prostate cancer showed increased and significant
expression for CCL18 (2.6-fold; p<0.001), a modest yet significant increase in
IL5 expression (1.17-fold; p=0.015), and a modest increase in CXCL5 expression
(1.4-fold; p=0.25). In conclusion, our studies demonstrate that sex steroid
hormones can induce aberrant gene expression via differential methylation changes
in prostate carcinogenesis.
PMID- 27500646
TI - Do arterial stiffness and wave reflections improve more with angiotensin receptor
blockers than with other antihypertensive drug classes?
PMID- 27500647
TI - Community-acquired pneumonia: the elusive quest for the best treatment strategy.
PMID- 27500648
TI - Comment on "Use of Carnosine for Oxidative Stress Reduction in Different
Pathologies".
PMID- 27500649
TI - The genetics of kinship in remote human groups.
AB - For fifteen years, part of the work of our research team has been focused on the
study of parental links between individuals living hundreds or thousands of years
ago, whose remains have been found in single graves or large funerary complexes.
These studies have been undertaken using methods developed by forensic genetics
to identify individuals, mainly based on the genotyping of autosomal STR (Short
Tandem Repeats). Issues arose from this work, namely the limits of studying small
numbers of subjects, originating from groups of finite sizes where kinships
cannot be inferred a priori and for which reference allelic frequencies do not
exist. Although ideal human populations are rare when undertaking such studies,
the Yakuts of Eastern Siberia constitute a very advantageous model, with large
numbers of small pastoral communities and well-preserved archaeological material.
The study of kinship in the ancient Yakuts allowed us to highlight the
difficulties in analysing genetic data from small ancient human groups and to
develop a strategy to improve the accuracy of statistical computations. This work
describes this strategy and possible solutions to the study of populations
outside of the frame of reference of global meta-populations, due either to
isolation, remoteness or antiquity.
PMID- 27500650
TI - Analysis of uni and bi-parental markers in mixture samples: Lessons from the 22nd
GHEP-ISFG Intercomparison Exercise.
AB - Since 1992, the Spanish and Portuguese-Speaking Working Group of the ISFG (GHEP
ISFG) has been organizing annual Intercomparison Exercises (IEs) coordinated by
the Quality Service at the National Institute of Toxicology and Forensic Sciences
(INTCF) from Madrid, aiming to provide proficiency tests for forensic DNA
laboratories. Each annual exercise comprises a Basic (recently accredited under
ISO/IEC 17043: 2010) and an Advanced Level, both including a kinship and a
forensic module. Here, we show the results for both autosomal and sex-chromosomal
STRs, and for mitochondrial DNA (mtDNA) in two samples included in the forensic
modules, namely a mixture 2:1 (v/v) saliva/blood (M4) and a mixture 4:1 (v/v)
saliva/semen (M8) out of the five items provided in the 2014 GHEP-ISFG IE.
Discrepancies, other than typos or nomenclature errors (over the total allele
calls), represented 6.5% (M4) and 4.7% (M8) for autosomal STRs, 15.4% (M4) and
7.8% (M8) for X-STRs, and 1.2% (M4) and 0.0% (M8) for Y-STRs. Drop-out and drop
in alleles were the main cause of errors, with laboratories using different
criteria regarding inclusion of minor peaks and stutter bands. Commonly used
commercial kits yielded different results for a micro-variant detected at locus
D12S391. In addition, the analysis of electropherograms revealed that the
proportions of the contributors detected in the mixtures varied among the
participants. In regards to mtDNA analysis, besides important discrepancies in
reporting heteroplasmies, there was no agreement for the results of sample M4.
Thus, while some laboratories documented a single control region haplotype, a few
reported unexpected profiles (suggesting contamination problems). For M8, most
laboratories detected only the haplotype corresponding to the saliva. Although
the GHEP-ISFG has already a large experience in IEs, the present multi-centric
study revealed challenges that still exist related to DNA mixtures
interpretation. Overall, the results emphasize the need for further research and
training actions in order to improve the analysis of mixtures among the forensic
practitioners.
PMID- 27500651
TI - Next generation sequencing of SNPs using the HID-Ion AmpliSeqTM Identity Panel on
the Ion Torrent PGMTM platform.
AB - The HID-Ion AmpliSeqTM Identity Panel (the HID Identity Panel) is designed to
detect 124-plex single nucleotide polymorphisms (SNPs) with next generation
sequencing (NGS) technology on the Ion Torrent PGMTM platform, including 90
individual identification SNPs (IISNPs) on autosomal chromosomes and 34 lineage
informative SNPs (LISNPs) on Y chromosome. In this study, we evaluated
performance for the HID Identity Panel to provide a reference for NGS-SNP
application, focusing on locus strand balance, locus coverage balance,
heterozygote balance, and background signals. Besides, several experiments were
carried out to find out improvements and limitations of this panel, including
studies of species specificity, repeatability and concordance, sensitivity,
mixtures, case-type samples and degraded samples, population genetics and
pedigrees following the Scientific Working Group on DNA Analysis Methods (SWGDAM)
guidelines. In addition, Southern and Northern Chinese Han were investigated to
assess applicability of this panel. Results showed this panel led to cross
reactivity with primates to some extent but rarely with non-primate animals.
Repeatable and concordant genotypes could be obtained in triplicate with one
exception at rs7520386. Full profiles could be obtained from 100pg input DNA, but
the optimal input DNA would be 1ng-200pg with 21 initial PCR cycles. A sample
with >=20% minor contributor could be considered as a mixture by the number of
homozygotes, and full profiles belonging to minor contributors could be detected
between 9:1 and 1:9 mixtures with known reference profiles. Also, this assay
could be used for case-type samples and degraded samples. For autosomal SNPs (A
SNPs), FST across all 90loci was not significantly different between Southern and
Northern Chinese Han or between male and female samples. All A-SNP loci were
independent in Chinese Han population. Except for 18loci with He <0.4, most of
the A-SNPs in the HID Identity Panel presented high polymorphisms. Forensic
parameters were calculated as >99.999% for combined discrimination power (CDP),
0.999999724 for combined power of exclusion (CPE), 1.390*1011 for combined
likelihood ratio (CLR) of trios, and 2.361*106 for CLR of motherless duos. For Y
SNPs, a total of 8 haplotypes were observed with the value of 0.684 for haplotype
diversity. As a whole, the HID Identity Panel is a well-performed, robust,
reliable and high informative NGS-SNP assay and it can fully meet requirements
for individual identification and paternity testing in forensic science.
PMID- 27500652
TI - Evanescent Field Based Photoacoustics: Optical Property Evaluation at Surfaces.
AB - Here, we present a protocol to estimate material and surface optical properties
using the photoacoustic effect combined with total internal reflection. Optical
property evaluation of thin films and the surfaces of bulk materials is an
important step in understanding new optical material systems and their
applications. The method presented can estimate thickness, refractive index, and
use absorptive properties of materials for detection. This metrology system uses
evanescent field-based photoacoustics (EFPA), a field of research based upon the
interaction of an evanescent field with the photoacoustic effect. This
interaction and its resulting family of techniques allow the technique to probe
optical properties within a few hundred nanometers of the sample surface. This
optical near field allows for the highly accurate estimation of material
properties on the same scale as the field itself such as refractive index and
film thickness. With the use of EFPA and its sub techniques such as total
internal reflection photoacoustic spectroscopy (TIRPAS) and optical tunneling
photoacoustic spectroscopy (OTPAS), it is possible to evaluate a material at the
nanoscale in a consolidated instrument without the need for many instruments and
experiments that may be cost prohibitive.
PMID- 27500653
TI - How a high working memory capacity can increase proactive interference.
AB - Previous findings suggested that a high working memory capacity (WMC) is
potentially associated with a higher susceptibility to proactive interference
(PI) if the latter is measured under high cognitive load. To explain such a
finding, we propose to consider susceptibility to PI as a net effect of
individual executive processes and the intrinsic potential for PI. With the
latter, we refer to the amount of information that is activated at a given time
and that has the potential to exert PI subsequently. In two studies deploying
generalized linear mixed models, susceptibility to PI was modeled as the decline
of performance over trials of a complex span task. The results revealed that a
higher WMC was associated with a higher susceptibility to PI. Moreover, the
number of stimuli recalled in one trial as a proxy variable for the intrinsic
potential for PI negatively affected memory performance in the subsequent trial.
PMID- 27500654
TI - Context-specific attentional sampling: Intentional control as a pre-requisite for
contextual control.
AB - Recent work suggests that environmental cues associated with previous attentional
control settings can rapidly and involuntarily adjust attentional priorities. The
current study tests predictions from adaptive-learning and memory-based theories
of contextual control about the role of intentions for setting attentional
priorities. To extend the empirical boundaries of contextual control phenomena,
and to determine whether theoretical principles of contextual control are
generalizable we used a novel bi-dimensional stimulus sampling task. Subjects
viewed briefly presented arrays of letters and colors presented above or below
fixation, and identified specific stimuli according to a dimensional (letter or
color) and positional cue. Location was predictive of the cued dimension, but not
the position or identity. In contrast to previous findings, contextual control
failed to develop through automatic, adaptive-learning processes. Instead,
previous experience with intentionally changing attentional sampling priorities
between different contexts was required for contextual control to develop.
PMID- 27500655
TI - Music chills: The eye pupil as a mirror to music's soul.
AB - This study evaluated whether music-induced aesthetic "chill" responses, which
typically correspond to peak emotional experiences, can be objectively monitored
by degree of pupillary dilation. Participants listened to self-chosen songs
versus control songs chosen by other participants. The experiment included an
active condition where participants made key presses to indicate when
experiencing chills and a passive condition (without key presses). Chills were
reported more frequently for self-selected songs than control songs. Pupil
diameter was concurrently measured by an eye-tracker while participants listened
to each of the songs. Pupil size was larger within specific time-windows around
the chill events, as monitored by key responses, than in comparison to pupil size
observed during 'passive' song listening. In addition, there was a clear
relationship between pupil diameter within the chills-related time-windows during
both active and passive conditions, thus ruling out the possibility that chills
related pupil dilations were an artifact of making a manual response. These
findings strongly suggest that music chills can be visible in the moment-to
moment changes in the size of pupillary responses and that a neuromodulatory role
of the central norepinephrine system is thereby implicated in this phenomenon.
PMID- 27500656
TI - Effective treatment via early cranioplasty for intractable contralateral subdural
effusion after standard decompressive craniectomy in patients with severe
traumatic brain injury.
AB - OBJECTIVE: This study aimed to introduce an effective treatment for intractable
contralateral subdural effusion after standard decompressive craniectomy in
patients with severe traumatic brain injury (TBI) and to analyze the underlying
mechanism. METHODS: A retrospective analysis was performed in 13 patients with
severe traumatic craniocerebral injury showing complicated intractable
contralateral subdural effusion after standard decompressive craniectomy, in whom
satisfactory results were not obtained from treatments, including compression
bandaging, head-down bed rest (HDBR), continuing lumbar drainage, and Ommaya
catheter drainage. Among these patients, 6 underwent temporal muscle sticking,
while 7 underwent early cranioplasty. The postoperative changes in the subdural
effusion were observed. RESULTS: In the 6 patients who underwent temporal muscle
sticking and the 7 who underwent early cranioplasty, the subdural effusion
completely resolved or was significantly reduced within one month, and no
recurrence was observed in the 6-month follow-up period. However, secondary
bilateral cranioplasty was still necessary in the postoperative 3-6 months for
the patients who underwent temporal muscle sticking. In the early cranioplasty
group, there were three total operations, and the average length of stay (ALOS)
was 76days. In the temporal muscle sticking group, there were four total
operations, and the ALOS was 56.1days. A retrospective analysis of surgical pain
showed that 100% of the patients in the first group experienced unacceptable
suffering, while 14.3% of the patients in the second group experienced pain.
CONCLUSION: Early cranioplasty is an effective, economical, and less painful
treatment for intractable contralateral subdural effusion after standard
decompressive craniectomy.
PMID- 27500658
TI - Protocols for treating patients with end-stage renal disease: a survey of
undergraduate dental programs.
AB - RATIONALE/BACKGROUND: Approximately 14% of Americans are living with chronic
kidney disease (CKD). The prevalence of end-stage renal disease (ESRD), the
result of progressing CKD continues to rise by 21,000 per year. There are no
updated, evidence-based antibiotic prophylaxis guidelines for patients with renal
disease undergoing dental treatment. The most recent was a scientific statement
from the American Heart Association (AHA) in 2003. Presented in three parts, the
goal of the first part of this study is to determine the current protocol being
used to treat renal patients at U.S. dental schools. METHODS AND MATERIALS: A 21
multiple-choice question survey was e-mailed to 58 clinic deans of accredited
dental schools in the United States regarding renal treatment protocol details
including antibiotic prophylaxis. RESULTS: Fifty-two percent of programs report
having no established renal patient treatment protocol. For programs with a
protocol, when using prophylactic antibiotics, 54% followed AHA protocol, whereas
62% used a modified protocol. CONCLUSION: There is a lack of consistent,
established protocols among undergraduate dental programs. It is suggested that
evidence-based guidelines for the safe treatment of patients be developed.
PMID- 27500657
TI - PL-PatchSurfer2: Improved Local Surface Matching-Based Virtual Screening Method
That Is Tolerant to Target and Ligand Structure Variation.
AB - Virtual screening has become an indispensable procedure in drug discovery.
Virtual screening methods can be classified into two categories: ligand-based and
structure-based. While the former have advantages, including being quick to
compute, in general they are relatively weak at discovering novel active
compounds because they use known actives as references. On the other hand,
structure-based methods have higher potential to find novel compounds because
they directly predict the binding affinity of a ligand in a target binding
pocket, albeit with substantially lower speed than ligand-based methods. Here we
report a novel structure-based virtual screening method, PL-PatchSurfer2. In PL
PatchSurfer2, protein and ligand surfaces are represented by a set of overlapping
local patches, each of which is represented by three-dimensional Zernike
descriptors (3DZDs). By means of 3DZDs, the shapes and physicochemical
complementarities of local surface regions of a pocket surface and a ligand
molecule can be concisely and effectively computed. Compared with the previous
version of the program, the performance of PL-PatchSurfer2 is substantially
improved by the addition of two more features, atom-based hydrophobicity and
hydrogen-bond acceptors and donors. Benchmark studies showed that PL-PatchSurfer2
performed better than or comparable to popular existing methods. Particularly, PL
PatchSurfer2 significantly outperformed existing methods when apo-form or
template-based protein models were used for queries. The computational time of PL
PatchSurfer2 is about 20 times shorter than those of conventional structure-based
methods. The PL-PatchSurfer2 program is available at
http://www.kiharalab.org/plps2/ .
PMID- 27500659
TI - Detection, seroprevalence and antimicrobial resistance of Yersinia enterocolitica
and Yersinia pseudotuberculosis in pig tonsils in Northern Italy.
AB - Yersiniosis is the third most common reported zoonoses in Europe, with Y.
enterocolitica and Y. pseudotuberculosis responsible for 98.66% and 0.94% of the
confirmed human cases in 2013. From June 2013 to October 2014, 201 pigs at
slaughter belonging to 67 batches were tested for Y. enterocolitica and Y.
pseudotuberculosis in tonsils. Diaphragm muscle samples were tested for
antibodies against Yersinia by a commercially available ELISA test. Y.
enterocolitica 4/O:3 was detected in 55/201 pig tonsils (27.4%; 95% CI 23.1
37.1). The positive pigs came from 38/67 batches (56.7%) and were reared in 36/61
farms (59.0%). There was no statistical difference between farrow-to-finish and
finishing farms. The mean count of Y. enterocolitica was 3.56+/-0.85log10CFU/g
with a minimum of 2.0log10CFU/g and a maximum of 4.78log10CFU/g. Y.
pseudotuberculosis was isolated from 4/201 pig tonsils (2.0%; 95% CI 0.0-4.5).
Three isolates belonged to serotype O:3 and one to serotype O:1. The positive
pigs belonged to 4/67 batches (6.0%) and came from finishing farms only. Y.
pseudotuberculosis could be enumerated in one sample only (4.27log10CFU/g). The
ELISA test demonstrated that 56.1% of the meat juice samples were positive for
Yersinia antibodies. Serological positivity was found in 67.9% (36/53) of the Y.
enterocolitica- and 75.0% (3/4) of the Y. pseudotuberculosis positive pigs. A
significant association was found between serological results and the presence of
Y. enterocolitica in tonsils (OR=1.97, p=0.044). All the Y. enterocolitica 4/O:3
isolates were susceptible to amoxicillin-clavulanic acid, gentamicin,
ceftazidime, ertapenem and meropenem, 94.5% to cefotaxime, 89.1% to kanamycin and
78.2% to tetracycline. The highest resistance rates were observed for ampicillin
(100%), sulphonamides (98.2%) and streptomycin (78.2%). Y. pseudotuberculosis
strains were sensitive to all the antimicrobials tested, i.e. amoxicillin,
amoxicillin/clavulanic acid, azithromycin, cephalothin, cefoxitin, ceftriaxone,
ciprofloxacin, nalidixic acid, sulphonamide, tetracycline and ticarcillin. The
study shows that Italian fattening pigs are frequently infected with human
pathogenic Y. enterocolitica 4/O:3. Although the isolation rate is slightly lower
than in other European countries, the serological test demonstrates that the
infection is widespread among pig population. In fact, seroprevalence is similar
to other EU countries. The detection of Y. pseudotuberculosis serotypes O:1 and
O:3 in pig tonsils is of concern. Since tonsils may represent a contamination
source for pig meat at slaughter, further studies regarding human infections by
both microbial species are strongly recommended.
PMID- 27500660
TI - Anxiety and quality of life after first-trimester termination of pregnancy: a
prospective study.
AB - INTRODUCTION: Possible effects of termination of pregnancy (TOP) on mental health
are a matter of debate. MATERIAL AND METHODS: We assessed anxiety and quality of
life during a one-year follow up after first-trimester TOP using the State-Trait
Anxiety Inventory (STAI) Scale and EuroQoL Quality of Life Questionnaire (EQ-5D,
EQ-VAS) in 742 women participating in a randomized controlled trial on early
provision of intrauterine contraception. The measurements were performed before
TOP, at 3 months and 1 year after TOP. Inclusion criteria were age >=18 years,
residence in Helsinki, duration of gestation <12 weeks, non-medical indication
for TOP, and approval of intrauterine contraception. The trial was registered
with Clinical Trials [NCT01223521]. RESULTS: When compared with baseline, the
overall anxiety level was significantly lower and quality of life higher at 3
months and at 1 year. Reduction of anxiety and improvement of quality of life was
especially evident (p < 0.001) in the 58% of women reporting clinically relevant
anxiety at baseline. High levels of anxiety at baseline, history of psychiatric
morbidity and smoking predicted significantly greater risk of poorer quality of
life and elevated level of anxiety during the follow up. CONCLUSIONS: TOP is
associated with a significant overall reduction of anxiety and an improvement of
quality of life among women undergoing it for non-medical indications. High
baseline anxiety, history of psychiatric morbidity and smoking are risk factors
of persistently high levels of anxiety and poor quality of life after an induced
abortion. These data are important when designing and providing post-abortion
care.
PMID- 27500661
TI - Multimorbidity and mortality in older adults: A systematic review and meta
analysis.
AB - OBJECTIVE: To review literature and provide a pooled effect for the association
between multimorbidity and mortality in older adults. METHODS: A systematic
review was performed of articles held on the PUBMED database published up until
January 2015. Studies which used different diseases and other conditions to
define frailty, evaluated multimorbidity related only to mental health or which
presented disease homogeneity were not included. A meta-analysis using random
effect to obtain a pooled effect of multimorbidity on mortality in older adults
was conducted only with studies which reported hazard ratio (HR). Stratified
analysis and univariate meta-regression were performed to evaluate sources of
heterogeneity. RESULTS: Out of 5806 identified articles, 26 were included in meta
analysis. Overall, positive association between multimorbidity and mortality [HR:
1.44 (95%CI: 1.34; 1.55)] was detected. The number of morbidities was positively
related to risk of death [HR: 1.20 (95%CI: 1.10; 1.30)]. Compared to individuals
without multimorbidity, the risk of death was 1.73 (95%CI: 1.41; 2.13) and 2.72
(95%CI: 1.81; 4.08) for people with 2 or more and 3 or more morbidities,
respectively. Heterogeneity between studies was high (96.5%). The sample,
adjustment and follow-up modified the associations. Only nine estimates performed
adjustment which included demographic, socioeconomic and behaviour variables.
Disabilities appear to mediate the effect of multimorbidity on mortality.
CONCLUSIONS: Multimorbidity was associated with an increase in risk of death.
Multimorbidity measurement standardization is needed to produce more comparable
estimates. Adjusted analysis which includes potential confounders might
contribute to better understanding of causal relationships between multimorbidity
and mortality.
PMID- 27500662
TI - Growth and Tunable Surface Wettability of Vertical MoS2 Layers for Improved
Hydrogen Evolution Reactions.
AB - Layered materials, especially the transition metal dichalcogenides (TMDs), are of
interest for a broad range of applications. Among the class of TMDs, molybdenum
disulfide (MoS2) is perhaps the most studied because of its natural abundance and
use in optoelectronics, energy storage and energy conversion applications.
Understanding the fundamental structure-property relations is key for tailoring
the enhancement in the above-mentioned applications. Here, we report a controlled
powder vaporization synthesis of MoS2 flower-like structures consisting of
vertically grown layers of MoS2 exhibiting exposed edges. This growth is readily
achievable on multiple substrates, such as graphite, silicon, and silicon
dioxide. The resulting MoS2 flowers are highly crystalline and stoichiometric.
Further observations using contact angle indicate that MoS2 flowers exhibit the
highest reported contact angle of ~160 +/- 10 degrees , making the material super
hydrophobic. This surface wettability was further tuned by changing the edge
chemistry of the MoS2 flowers using an ozone etching treatment. Hydrogen
evolution reaction (HER) measurements indicate that the surface treated with UV
ozone showed a reduction in the Tafel slope from 185 to 54 mV/dec, suggesting an
increase in the amount of reactive surface to generate hydrogen.
PMID- 27500663
TI - Predicting Financial Distress and Closure in Rural Hospitals.
AB - PURPOSE: Annual rates of rural hospital closure have been increasing since 2010,
and hospitals that close have poor financial performance relative to those that
remain open. This study develops and validates a latent index of financial
distress to forecast the probability of financial distress and closure within 2
years for rural hospitals. METHODS: Hospital and community characteristics are
used to predict the risk of financial distress 2 years in the future. Financial
and community data were drawn for 2,466 rural hospitals from 2000 through 2013.
We tested and validated a model predicting a latent index of financial distress
(FDI), measured by unprofitability, equity decline, insolvency, and closure.
Using the predicted FDI score, hospitals are assigned to high, medium-high,
medium-low, and low risk of financial distress for use by practitioners.
FINDINGS: The FDI forecasts 8.01% of rural hospitals to be at high risk of
financial distress in 2015, 16.3% as mid-high, 46.8% as mid-low, and 28.9% as low
risk. The rate of closure for hospitals in the high-risk category is 4 times the
rate in the mid-high category and 28 times that in the mid-low category. The
ability of the FDI to discriminate hospitals experiencing financial distress is
supported by a c-statistic of .74 in a validation sample. CONCLUSION: This
methodology offers improved specificity and predictive power relative to existing
measures of financial distress applied to rural hospitals. This risk assessment
tool may inform programs at the federal, state, and local levels that provide
funding or support to rural hospitals.
PMID- 27500664
TI - Masting behaviour in a Mediterranean pine tree alters seed predator selection on
reproductive output.
AB - Context-dependency in species interactions is widespread and can produce
concomitant patterns of context-dependent selection. Masting (synchronous
production of large seed crops at irregular intervals by a plant population) has
been shown to reduce seed predation through satiation (reduction in rates of seed
predation with increasing seed cone output) and thus represents an important
source of context-dependency in plant-animal interactions. However, the
evolutionary consequences of such dynamics are not well understood. Here we
describe masting behaviour in a Mediterranean model pine species (Pinus pinaster)
and present a test of the effects of masting on selection by seed predators on
reproductive output. We predicted that masting, by enhancing seed predator
satiation, could in turn strengthen positive selection by seed predators for
larger cone output. For this we collected six-year data (spanning one mast year
and five non-mast years) on seed cone production and seed cone predation rates in
a forest genetic trial composed by 116 P. pinaster genotypes. Following our
prediction, we found stronger seed predator satiation during the masting year,
which in turn led to stronger seed predator selection for increased cone
production relative to non-masting years. These findings provide evidence that
masting can alter the evolutionary outcome of plant-seed predator interactions.
More broadly, our findings highlight that changes in consumer responses to
resource abundance represent a widespread mechanism for predicting and
understanding context dependency in plant-consumer evolutionary dynamics.
PMID- 27500665
TI - A comparison of techniques for studying oogenesis in the European eel Anguilla
anguilla.
AB - A multi-technique approach was used to study the changes occurring in European
eel Anguilla anguilla ovaries during hormonally-induced vitellogenesis. Aside
from classic techniques used to monitor the vitellogenic process, such as ovary
histology, fat content analysis, sodium dodecyl sulphate-polyacrylamide gel
electrophoresis (SDS-PAGE) and vitellogenin enzyme linked immunosorbent assay
(ELISA), a new technique, Fourier-transform infrared (FT-IR) microspectroscopy,
was used to analyse A. anguilla ovaries. The results from the different
techniques provided different ways of approaching the same process. Although it
is considered a time consuming approach, of all the employed techniques,
histology provided the most direct evidences about vitellogenesis. SDS-PAGE and
ELISA were also useful for studying vitellogenesis, whereas fat analysis cannot
be used for this purpose. The FT-IR analysis provided a representative IR
spectrum for each ovarian stage (previtellogenic stage, early vitellogenic stage,
mid-vitellogenic stage and late vitellogenic stage), demonstrating that it is a
valid method able to illustrate the distribution of the oocytes within the ovary
slices. The chemical maps obtained confirmed changes in lipid concentrations and
revealed their distribution within the oocytes at different maturational stages.
When the results and the accuracy of the FT-IR analysis were compared with those
of the traditional techniques commonly used to establish the vitellogenic stage,
it became evident that FT-IR is a useful and reliable tool, with many advantages,
including the fact that it requires little biological material, the costs
involved are low, analysis times are short and last but not least, the fact that
it offers the possibility of simultaneously analysing various biocomponents of
the same oocyte.
PMID- 27500667
TI - High-Performance Photovoltaic Polymers Employing Symmetry-Breaking Building
Blocks.
AB - Two 1D-2D asymmetric benzodithiophenes (BDTs) as donor building blocks are
designed and synthesized, combining the advantages of both 1D and 2D symmetric
BDTs. The photovoltaic properties of the asymmetric BDT-based polymers are
improved greatly in comparison with corresponding symmetric BDT-based polymers.
This work provides a new approach to design prospective organic optoelectronic
materials employing the symmetry-breaking strategy.
PMID- 27500666
TI - Impact of Massachusetts Health Reform on Inpatient Care Use: Was the Safety-Net
Experience Different Than in the Non-Safety-Net?
AB - OBJECTIVE: Most inpatient care for the uninsured and other vulnerable
subpopulations occurs in safety-net hospitals. As insurance expansion increases
the choice of hospitals for the previously uninsured, we examined if
Massachusetts health reform was associated with shifts in the volume of inpatient
care from safety-net to non-safety-net hospitals overall, or among other
vulnerable sociodemographic (racial/ethnic minority, low socioeconomic status,
high uninsured rate area) and clinical subpopulations (emergent status,
diagnosis). DATA SOURCES/STUDY SETTING: Discharge records for adults discharged
from all nonfederal acute care hospitals in Massachusetts, New Jersey, New York,
and Pennsylvania 2004-2010. STUDY DESIGN: Using a difference-in-differences
design, we compared pre-/post-reform changes in safety-net and non-safety-net
hospital discharge outcomes in Massachusetts among adults 18-64 with
corresponding changes in comparisons states with no reform, overall, and by
subpopulations. PRINCIPAL FINDINGS: Reform was not associated with changes in
inpatient care use at safety-net and non-safety-net hospitals across all
discharges or in most subpopulations examined. CONCLUSIONS: Demand for inpatient
care at safety-net hospitals may not decrease following insurance expansion.
Whether this is due to other access barriers or patient preference needs to be
explored.
PMID- 27500668
TI - Influence of insurance status on survival of adults with glioblastoma multiforme:
A population-based study.
AB - BACKGROUND: To the authors' knowledge, the impact of insurance status on the
survival time of patients with glioblastoma multiforme (GBM) has not been fully
understood. The objective of the current study was to clarify the association
between insurance status and survival of patients with GBM by analyzing
population-based data. METHODS: The authors performed a cohort study using data
from the Surveillance, Epidemiology, and End Results program. They included adult
patients (aged >=18 years) with GBM as their primary diagnosis from the years
2007 to 2012. Patients without information regarding insurance status were
excluded. A survival analysis between insurance status and GBM-related death was
performed using an accelerated failure time model. Demographic and clinical
variables were included to adjust for confounding effects. RESULTS: Among the
13,665 adult patients in the study cohort, 558 (4.1%) were uninsured, 1516
(11.1%) had Medicaid coverage, and 11,591 (84.8%) had non-Medicaid insurance.
Compared with patients who were uninsured, insured patients were more likely to
be older, female, white, married, and with a smaller tumor size at diagnosis.
Accelerated failure time analysis demonstrated that older age (hazard ratio [HR],
1.04; P<.001), male sex (HR, 1.08; P<.001), large tumor size at the time of
diagnosis (HR, 1.26; P<.001), uninsured status (HR, 1.14; P =.018), and Medicaid
insurance (HR, 1.10; P =.006) were independent risk factors for shorter survival
among patients with GBM, whereas radiotherapy (HR, 0.40; P<.001) and married
status (HR, 0.86; P<.001) indicated a better outcome. The authors discovered an
overall yearly progressive improvement in survival in patients with non-Medicaid
insurance who were diagnosed from 2007 through 2011 (P =.015), but not in
uninsured or Medicaid-insured patients. CONCLUSIONS: Variations existed in
insurance status within the GBM population. Uninsured status and Medicaid
insurance suggested shorter survival compared with non-Medicaid insurance among a
population of patients with GBM. Cancer 2016;122:3157-65. (c) 2016 American
Cancer Society.
PMID- 27500669
TI - Jasmonate-mediated stomatal closure under elevated CO2 revealed by time-resolved
metabolomics.
AB - Foliar stomatal movements are critical for regulating plant water loss and gas
exchange. Elevated carbon dioxide (CO2 ) levels are known to induce stomatal
closure. However, the current knowledge on CO2 signal transduction in stomatal
guard cells is limited. Here we report metabolomic responses of Brassica napus
guard cells to elevated CO2 using three hyphenated metabolomics platforms: gas
chromatography-mass spectrometry (MS); liquid chromatography (LC)-multiple
reaction monitoring-MS; and ultra-high-performance LC-quadrupole time-of-flight
MS. A total of 358 metabolites from guard cells were quantified in a time-course
response to elevated CO2 level. Most metabolites increased under elevated CO2 ,
showing the most significant differences at 10 min. In addition, reactive oxygen
species production increased and stomatal aperture decreased with time. Major
alterations in flavonoid, organic acid, sugar, fatty acid, phenylpropanoid and
amino acid metabolic pathways indicated changes in both primary and specialized
metabolic pathways in guard cells. Most interestingly, the jasmonic acid (JA)
biosynthesis pathway was significantly altered in the course of elevated CO2
treatment. Together with results obtained from JA biosynthesis and signaling
mutants as well as CO2 signaling mutants, we discovered that CO2 -induced
stomatal closure is mediated by JA signaling.
PMID- 27500670
TI - An updated systematic review of epidemiological evidence on hormonal
contraceptive methods and HIV acquisition in women.
AB - OBJECTIVE AND DESIGN: Some studies suggest that specific hormonal contraceptive
methods [particularly depot medroxyprogesterone acetate (DMPA)] may increase
women's HIV acquisition risk. We updated a systematic review to incorporate
recent epidemiological data. METHODS: We searched for articles published between
15 January 2014 and 15 January 2016 and hand-searched reference lists. We
identified longitudinal studies comparing users of a specific hormonal
contraceptive method against either nonusers of hormonal contraception or users
of another specific hormonal contraceptive method. We added newly identified
studies to those in the previous review, assessed study quality, created forest
plots to display results, and conducted a meta-analysis for data on DMPA versus
non-use of hormonal contraception. RESULTS: We identified 10 new reports of which
five were considered 'unlikely to inform the primary question'. We focus on the
other five reports, along with nine from the previous review, which were
considered 'informative but with important limitations'. The preponderance of
data for oral contraceptive pills, injectable norethisterone enanthate, and
levonorgestrel implants do not suggest an association with HIV acquisition,
though data for implants are limited. The new, higher quality studies on DMPA (or
nondisaggregated injectables), which had mixed results in terms of statistical
significance, had hazard ratios between 1.2 and 1.7, consistent with our meta
analytic estimate for all higher quality studies of hazard ratio 1.4. CONCLUSION:
Although confounding in these observational data cannot be excluded, new
information increases concerns about DMPA and HIV acquisition risk in women. If
the association is causal, the magnitude of effect is likely hazard ratio 1.5 or
less. Data for other hormonal contraceptive methods, including norethisterone
enanthate, are largely reassuring.
PMID- 27500671
TI - A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes
Implicated in Human Diseases of Aging.
AB - Age-related diseases are becoming increasingly prevalent and the burden continues
to grow as our population ages. Effective treatments are necessary to lessen the
impact of debilitating conditions but remain elusive in many cases. Only by
understanding the causes and pathology of diseases associated with aging, can
scientists begin to identify potential therapeutic targets and develop strategies
for intervention. The most common age-related conditions are neurodegenerative
disorders such as Parkinson's disease and blindness. Age-related macular
degeneration (AMD) is the leading cause of blindness in the elderly. Genome wide
association studies have previously identified loci that are associated with
increased susceptibility to this disease and identified two regions of interest:
complement factor H (CFH) and the 10q26 locus, where the age-related maculopathy
susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HtrA1) genes
are located. CFH acts as a negative regulator of the alternative pathway (AP) of
the complement system while HtrA1 is an extracellular serine protease. ARMS2 is
located upstream of HtrA1 in the primate genome, although the gene is absent in
mice. To study the effects of these genes, humanized knock-in mouse lines of Cfh
and ARMS2, knockouts of Cfh, HtrA1, HtrA2, HtrA3 and HtrA4 as well as a
conditional neural deletion of HtrA2 were generated. Of all the genetically
engineered mice produced only mice lacking HtrA2, either systemically or in
neural tissues, displayed clear phenotypes. In order to examine these mice
thoroughly and systematically, an initial phenotyping schedule was established,
consisting of a series of tests related to two main diseases of interest: AMD and
Parkinson's. Genetically modified mice can be subjected to appropriate
experiments to identify phenotypes that may be related to the associated diseases
in humans. A phenotyping regimen with a mitochondrial focus is presented here
alongside representative results from the tests of interest.
PMID- 27500672
TI - [The application of the system of "reminder stickers" for the rehabilitation
programs with the use of behavioural therapy for the patients presenting with
anxiety disorders].
AB - This article was designed to report the results of research on the effectiveness
of the new original "reminder stickers" technique proposed by the authors for the
management of the patients undergoing rehabilitation based on behavioral therapy.
The essence of this technique consists of providing the patients with systematic
reminders of the need to implement skills aimed at coping with maladaptive
sensations that accompany anxiety disorders. AIM: The objective of the present
study was to evaluate the effectiveness of using the "reminder stickers"
technique for the formation of stable responses to the correction of the target
clinical symptoms. PATIENTS AND METHODS: The study involved 118 patients
suffering from anxiety disorders allocated to two groups for comparison. Group 1
was comprised of the patients (n=76) given the reminders while group 2 contained
those (n=42) not included in the system of "reminder stickers". The difference
between the parameters of interest in the two groups was estimated with the use
of Mann-Whitney and Kolmogorov-Smirnov tests. RESULTS: The analysis of diary
records of the patients was used to evaluate the frequency of occurrence of
maladaptive sensations that required the application of the appropriate
behavioural skills and the frequency of the missed or delayed responses as well
as the level of subjective satisfaction of the patients with the stability of the
acquired skills. It was shown that the patients given "reminder stickers"
significantly more frequently reported situations that required the application
of the appropriate skills within the first week after the initiation of
monitoring than the patients of group 2 (r<0,0001). The frequency of the missed
or delayed responses in these patients was significantly lower than in group 2
(r<0,0001) whereas the degree of subjective satisfaction with the stability of
the acquired skills was much higher (r<0,0001). These differences persisted
during week 2 after the onset of monitoring when the frequency of maladaptive
sensations that required the application of the previously formed behavioural
skills of therapeutic significance in the patients given "reminder stickers"
remained lower than in the patients to whom no such "remainders" were provided
(r=0,001). The frequency of the missed or delayed responses in these patients
decreased significantly in comparison with that in group 2 (r<0,0001),) while the
degree of subjective satisfaction of the patients with the stability of the
acquired skills further increased (r<0,0001). CONCLUSION: The results of the
study indicate that inclusion of "reminder stickers" in the structure of
cognitive-behavioral therapy at the stages of formation of the skills needed to
cope with maladaptive sensations enhances the ability of the patients presenting
with anxiety disorders to much more often timely identify situations that require
the use of the appropriate behavioural skills and to apply them. It is concluded
that the application of the original "reminder stickers" technique ensures an
adequate response of the patients to maladaptive sensations that accompany
anxiety disorders.
PMID- 27500673
TI - [The analysis of compliance of pharmacotherapy of patients with myocardial
infarction to the principles evidence-based medicine at the stage of
rehabilitation in modern conditions].
AB - GOAL: Acute myocardial infarction is one of the causal factors of society and
economic losses of companionship. Success in the treatment of acute myocardial
infarction raises questions on the effective rehabilitation of the first places.
New methods, clinical guidelines and standards have been introduced into clinical
practice. However, the effectiveness of rehabilitation in the Russian Federation
lower than developed countries. The present study was aimed to improve
rehabilitation care to patients after acute myocardial infarction. Analysis of
the effectiveness of rehabilitation and pharmacoepidemiological studies was
conducted on the basis of a medical spa facility in 2006 and 2009. MATERIAL AND
METHODS: Experts form and database were developed to achieve the objectives.
Quantitative assessments were carried out on the basis of the developed quality
indicators. We used pharmacoepidemiological and statistical methods in the study.
RESULTS: Myocardial infarction was often combined with hypertension (73.8% and
61.9%) and chronic heart failure (87.6% and 85.8%). Patients had a high
prevalence of risk factors: smoking (46.1% and 42.3%), overweight (53.8% and
67.2%), dyslipidemia (44.6% and 66.1%) in 2006 and 2009, respectively.
Rehabilitation includes physical exercise, mineral baths, swimming pool. The
average number of drugs of rehabilitation stage was 4,46+/-0,12 and 4,11+/-0,11.
Beta-blockers are indicated for all patients after acute myocardial infarction,
and they were prescribed in 86.1% and 90.1% of cases. Drugs affecting renin
angiotensin system were in second place frequency of prescribing. These drugs are
prescribed in 67.6% and 41.7% patients. The frequency of prescribing of statins
increased by 5.8 times from 2006 to 2009 and reached 81.32%. CONCLUSION:
Rehabilitation and pharmacotherapy in patients after acute myocardial infarction
corresponds to the principle evidence-based medicine. However, the list of use
drugs was narrow, and the doses were lower than recommended by current clinical
guidelines. These facts may indicate a deficiency of awareness of doctors around
the characteristics of drug usage. Standards of health - resort treatment and
rehabilitation of patients after myocardial infarction is limited and their
revision is required based on existing clinical guidelines and evidence-based
medicine.
PMID- 27500674
TI - [The systemic approach to the health protection in the workers of industrial
enterprises].
AB - This paper presents the results of the systemic approach to the protection of
health and prophylaxis of disability in the workers of industrial enterprises.
The leading role in the technologies of rehabilitation (both short-term and long
term one) is played by the natural and physical therapeutic factors. The priority
in the implementation of the therapeutic and health-promoting measures is given
to the treatment based on the spa and health resort facilities as well as the
factory health centers.
PMID- 27500675
TI - [The substantiation of the use of high-frequency intrapulmonary ventilation in
the patients presenting with chronic obstructive pulmonary disease at the spa and
health resort stage of rehabilitation].
AB - The importance of the development of the new methods for the rehabilitation of
the patients presenting with chronic obstructive pulmonary disease under
conditions of the spa and health resort-based treatment arises from the high
prevalence and the progressive character of this disease, poor quality of the
patients' life, great economic losses due to the reduction of the working
capacity of the patients, and the high cost of COPD treatment. AIM: The objective
of the present study was to substantiate the advisability of inclusion of high
frequency intrapulmonary ventilation in the program of the therapeutic and
rehabilitative treatment of the patients with COPD based at a spa and health
resort facility. PATIENTS AND METHODS: The analysis of the results of examination
and rehabilitative treatment included 49 patients treated at the "Belokurikha"
health resort (14 women and 35 men presenting with stage 1 and 2 COPD). The
patients were divided into two groups. The main one included 23 patients while
the group of comparison consisted of 26 patients. Those of the main group were
given the treatment that included the mineral water baths, inhalations, exercise
therapy for the training of skeletal muscles, manual massage, high-frequency
intrapulmonary ventilation, intake of extract maral root (Rhaponticum
carthamoides) and the "Yantar antiox" (amber antiox) preparation. The patients of
the comparison group received the same rehabilitative treatment but without high
frequency intrapulmonary ventilation. The effectiveness of the rehabilitative
measures was comprehensively estimated from the dynamics of the clinical data,
indices of the inflammatory activity, the results of spirography and 6 minute
walking test. RESULTS: It has been shown that the introduction of high-frequency
intrapulmonary ventilation into the spa and health resort-based rehabilitative
program facilitates the elimination of clinical manifestation of the disease,
promotes recovery of the external respiration function due to sputum recruiting
and stimulation of mucociliary clearance that in turn decreases the activity of
the inflammatory processes. Simultaneously, the thoracic mobility and physical
efficiency of the patients increased. The overall result of the treatment was the
enhanced quality of rehabilitation of the patients suffering COPD within 14-16
days of their stay at the health resort with excellent tolerability of the
proposed therapeutic modality.
PMID- 27500676
TI - [Analysis of the effectiveness of the spa and health resort-based treatment of
the patients presenting with broncho-pulmonary pathology at the southern coast of
the Crimea depending on the period of flowering of Mediterranean Cypress
(Cupressus sempervirens)].
AB - AIM: The objective of the present study was to evaluate the influence of pollen
of Mediterranean Cypress (Cupressus sempervirens) on the effectiveness of the spa
and health resort-based treatment (SHRT) of the patients with broncho-pulmonary
pathology at the southern coast of the Crimea (SCC). MATERIAL AND METHODS: This
article presents the results of the analysis of the data on 122 patients
presenting with broncho-pulmonary pathology who received SHRT under the
conditions of the Southern Coast of the Crimea. Fifty one (41.8%) of these
patients suffered from chronic obstructive pulmonary disease and 71 (58.2%) ones
had bronchial asthma. The whole group was comprised of 44 men (36.1%) and 78
women (63.9%). The average (median) age of the patients was 55.8 years. All the
participants of the study underwent the comprehensive examination including the
general medical and physical examination, complete blood count, the study of
sputum cytology and immunological properties of blood including the standard
characteristics, IgE and lysozyme levels), evaluation of the respiratory and
locomotor (physical) functions with the use of the 6-minute walking test.
RESULTS: The aeropollenological study of the aerial environment of the southern
coast of the Crimea in the region of Yalta showed that the "bloom" of the
Mediterranean Cypress occurs during the period from February till April
inclusive. The highest concentrations of cypress pollen are observed in March and
early April. The overall effectiveness of SHRT for the patients with broncho
pulmonary pathology arriving for the treatment at the southern coast of the
Crimea from other Crimean localities does not depend on the period of "flowering"
(the presence of pollen in the air) of the Mediterranean Cypress. In these
patients, the termination of the spa and health resort-based treatment during the
"flowering" of the Mediterranean Cypress resulted in nothing more than a strained
adaptive response manifested as the altered blood leukocyte count. Such reaction
is considered to be a natural consequence of intake of antigenic substances into
the human body.
PMID- 27500677
TI - [The contingency of the therapeutic effectiveness with the peculiarities of the
non-pharmacological treatment of the patients presenting with chronic
cholecystitis].
AB - The elaboration of new technologies for the medical rehabilitation of the
patients presenting with chronic cholecystitis in combination with chronic
opisthorchiasis is a topical problem facing modern clinical gastroenterology. The
application of up-to-date non-pharmacological therapeutic modalities, such as
ultrahigh-frequency (UHF) therapy concomitantly with group chronophysiotherapy
makes it possible to significantly improve the final outcome of the treatment.
The results of clinical studies give evidence of the favourable influence of the
combined chronorehabilitative treatment including UHF therapy on the
characteristics of the functional state of the biliary-hepatic system and of the
organism as a whole. The positive dynamics of these characteristics is suggestive
of the high (up to 87,5%) therapeutic effectiveness of the proposed treatment.
The investigations into the relationship between this effect and the
peculiarities of the combined therapeutic modalities have demonstrated their
correlation (chi2=104,13; p=0,0001; V-Kramer's coefficient =0,35) and showed that
the use of combined chronorehabilitation including UHF therapy based on the
application of phone resonance radiation guarantees (and is a predictor of) high
therapeutic effect (percent concordance =95,6%; standard coefficient=2,13;
p=0,001) of the treatment of the patients with chronic cholecystitis in
combination with chronic opisthorchiasis. The statistical analysis of the results
of application of the modern non-pharmacological therapeutic modalities and the
chronobiological approach for the purpose of the combined treatment of patients
presenting with chronic cholecystitis in combination with opisthorchiasis with
the use of contingency table and logit regression, allowed not only to estimate
the interdependence and interrelation between the characteristics of interest but
also to reveal predictors of therapeutic effectiveness. These findings are of
great practical importance since they can be used for the choice of therapeutic
strategies for the management of this category of patients.
PMID- 27500678
TI - [The prospects for the application of the natural and preformed therapeutic
factors in the treatment of non-alcoholic fatty liver disease].
AB - Non-alcoholic fatty liver disease (NAFLD) is one of the most widespread diffuse
liver pathologies among the patients over 40 years of age. The available
algorithms for the pharmacological treatment of this disease do not always ensure
the desirable results which makes their further development and improvement with
the use of natural and preformed physical factors an important priority. AIM: The
objective of the present study was to evaluate the effectiveness of the internal
course of mineral waters of different balneological types and a bischofite
aqueous solution for the treatment of the patients presenting with NAFLD.
PATIENTS AND METHODS: A total of 120 patients with non-alcoholic fatty liver
disease were examined and treated with the use of the anamnestic, clinical,
biochemical and immunochemical methods as well as sonographic studies of the
digestive system and the statistical analysis. RESULTS: The data on the
effectiveness of the use of mineral waters of different balneological types and a
bischofite aqueous solution in the treatment of NAFLD are presented. It is shown
that the use of an aqueous solution of bischofite improves the clinical course of
the underlying disease (p<0.05), concomitant diseases of the biliary tract
(p<0.02) and irritable bowl syndrome complicated by constipation (p<0.003); also,
it improves the functional state of the liver and the blood lipid profile
(p<0.02) and significantly reduces insulin resistance (p<0.01), primarily due to
the reduction of hyperinsulinemia (p<0.01). Using the mineral waters with the
predominance of sulfates can improve the clinical course of liver diseases
(p<0.01), biliary tract and intestines (p<0.02), normalize the functional state
of the liver including that in the patients with non-alcoholic steatohepatitis
(p<0.05,) significantly improve the blood lipid profile (p<0.02) due to the
substantial improvement of disordered carbohydrate metabolism including that in
the patients suffering from type 2 diabetes mellitus (p<0.05). The application of
mineral waters with the elevated content of hydrocarbons improves the clinical
course of NAFLD with the concomitant esophagogastroduodenal pathology (p<0.001)
and simultaneously reduces the severity of insulin resistance due to the lowering
of the level of hyperinsulinemia (p<0.001). Moreover, the mineral water-based
therapy improves tolerance to carbohydrates, in the first place in the patients
with type 2 diabetes mellitus (p<0.01), and restores the background lipid profile
(p<0.05). CONCLUSION: The studies has demonstrated the high efficiency of the non
pharmacological treatment resulting in the multifaceted and oppositely
directional influence on the patients presenting with non-alcoholic fatty liver
disease. The possibility of the differentiated application of mineral water and
an aqueous solution of bischofite for the treatment of this pathology is
confirmed depending on the stage of the disease, the severity of metabolic
disorders, the presence of a concomitant pathology of the digestive system, type
2 diabetes mellitus, and hypertension.
PMID- 27500680
TI - [The investigation of immunological effects of the new balneotherapeutic
preparation glinofir used for the treatment of adjuvant arthritis].
AB - AIM: The objective of the present study was to investigate the influence of a
course of application of the modified natural factors on the immunological
mechanisms of regulation under experimental conditions with special reference to
the application of the natural yellow clay, the clay from the Novo-Pyatigorsk
quarry (the lake Tambokan) and of the new balneotherapeutic preparation glinofir
based on this modified clay and designed for the treatment of adjuvant arthritis
(AA). MATERIAL AND METHODS: The study of anti-inflammatory activity of the
externally applied balneomedicines was carried out with the use of an animal
model of adjuvant arthritis. The course of applications started 3 days prior to
the initiation of AA and was terminated on the 24th day of the experimental
disease. The action of three balneotherapeutic preparations (Tambukan mud, yellow
clay, and modified clay in the form of Glinofir) was compared after they were
heated to 42 degrees C and applied to the animals' limbs for 15-20 minutes every
second and third days. The experiments were performed on Wistar rats (n=59)
divided into five groups. Group 1 was comprised of 9 healthy animals that served
as controls. The animals of group 2 (n=10) presented with untreated
experimentally-induced adjuvant arthritis, those of Group 3 (n=10) had model AA
treated by a course of application of the Tambukan mud. The animals of group 4
(n=10) had model AA and were treated by the application of the yellow clay and
those of Group 5 (n=10) with model of AA received a course of application of the
modified clay. RESULTS: On day 37 after the induction of adjuvant arthritis, the
animals developed leukocytosis (white blood cell count in the blood was 1.5 times
higher than in the control group) and alterations in the composition of the
lymphocyte population, viz. B-lymphocytes increased 2-2.5 times (p<0,02) while T
lymphocytes decreased (p<0,05). A course of glinofir application contributed to
the restoration of the T-cytotoxic cell population (p<0,2) and influenced the
regulation of pathological immune complexes (PIC) as confirmed the negative
correlation between the PIC level and the absolute number of T-cytotoxic cells
(r=-0,8, p<0,01). The chronic stage of AA was associated with a two-fold increase
in the absorptive capacity of neutrophils. The treatment with the Tambukan mud
and glinofir restored the phagocytic function of neutrophils and simultaneously
reduced the blood leukocyte reaction. CONCLUSION: The anti-inflammatory action of
the Tambukan mud and glinofir manifests itself in the unidirectional changes of
dynamics of the characteristics of cellular and humoral immunity.
PMID- 27500679
TI - [The application of the preformed physical factors for the combined treatment of
the patients presenting with chronic vesiculitis].
AB - The problem of the development of the new efficient methods for the treatment of
the patients presenting with chronic bacterial vesiculitis (CBV) is currently
considered among the important priorities. AIM: The objective of the present
study was to provide a scientifically sound substantiation for the application of
sinusoidal modulated currents (SMC), magnetic fields, and laser radiation in the
combined treatment of the patients with CBV. PATIENTS AND METHODS: A total of 121
patients presenting with chronic bacterial vesiculitis were examined and treated
during the latent phase of the inflammatory process. They were randomly divided
into three groups. Group 1 (main) was comprised of 40 patients treated, in
addition to basal pharmacotherapy, by supravascular contact laser irradiation of
the cubital vein area followed after 2-3 hours by the application of sinusoidal
modulated currents to the pubosacral region. Group 2 included 41patents given,
besides basal pharmacotherapy, laser therapy in the same regimen as in group 1
supplemented after 2-3 hours by abdominal magnetic therapy. Group 3 (control)
received traditional pharmacotherapy in the combination with antibacterial and
anti-inflammatory medicines. RESULTS: It was demonstrated that the patients of
group 2 exhibited the most pronounced positive dynamics of the clinical signs and
symptoms estimated from the total National Institute of Health Chronic
Prostatitis Symptom Index (NIH-CPSI) and of the characteristics of the quality of
life evaluated based on the QLS scale. The patients of the two former groups
experienced a more conspicuous decrease in the activity of the inflammatory
process in seminal vesicles, restoration of their structural and anatomical
features (as shown by the transrectal ultrasound study), improvement of
testosterone metabolism, and normalization of the spermogram characteristics in
comparison with controls. The analysis of the spermograms revealed the tendency
toward the increase in the number of actively motile spermatozoa only in the
patients of group 2. The combined treatment of the patients of the two former
groups resulted in the decrease of the level of sex hormone-binding globulin and
the increase of the free androgen index. CONCLUSION: The results of the study
indicate that the application of the preformed physical factors for the treatment
of the patients presenting with chronic bacterial vesiculitis enhances the
effectiveness of pharmacotherapy and decreases both the frequency and the
duration of relapses of the disease.
PMID- 27500681
TI - [The natural therapeutic resources of Russia: the topical problems].
AB - Mineral water, therapeutic peloids, favorable landscape and climatic conditions
make up the main basis for the creation and development of the health resort
business. Mineral water and therapeutic peloids are mineral resources, their
prospecting, discovery, exploration and stock assessment of the responsibility of
the Geological Survey of the country while the exploration and practical
exploitation of the natural medicinal resources is the prerogative of the users
of subsurface resources. At present, there are over 1200 deposits of mineral
waters as well as more than 260 sources of therapeutic peloids at the territory
of the Russian Federation; the include almost all hydrochemical species and types
known and exploited in the world's practice The overall picture of the
distribution of the potential and developed deposits of mineral waters and
therapeutic peloids of the territory of this country is highly non-uniform and
depends on the extent of the economic development of different regions, their
geographical and climatic conditions as well as the state and availability of the
spa and health resort infrastructure. The natural therapeutic resources,
territories suitable for the organization and realization of health promoting
activities, setting up new spa and health resort facilities are highly vulnerable
to any external impact. We possess the scientifically grounded and practice
proven methods for the search, prospecting, practical development, and medical
utilization of various natural therapeutic resources as well as technologies for
their conservation, restoration, and protection from damages and
overexploitation. The rational use and development of the territories promising
for the extension of health resort business imply the necessity of the systemic
approach in a consistent stage by stage manner based of the reliable prognoses.
PMID- 27500682
TI - Key factors of scanning a plant virus with AFM in air and aqueous solution.
AB - For tobacco mosaic virus (TMV) as a model virus, this article shows typical
issues of scanning soft biological matter by atomic force microscopy (AFM). TMV
adsorbed on chemically different flat surfaces, gold, mica, and APDMES
functionalized silicon, is studied in air and aqueous environment. In air, the
TMV particles arrangement shows some variety, depending on the substrate. The
height of TMV is reduced to 13.7, 15.8, and 15.6 nm, for gold, APDMES, and mica,
respectively while the width is about ~30 nm due to the influence of the tip
radius. In aqueous solution, the surface charges of the virus and the solid
support play an important role in the virus adsorption process. While deposition
on negatively charged mica is favored only at low pH values, it is shown that
positively charged APDMES functionalized silicon can be a suitable substrate to
work with at neutral pHs. The effects of cantilever oscillation's free amplitude
(A0 ) and the amplitude set-point (A) are also assessed here. While high A0
prompt reversible deformation of TMV in measurements performed in air,
irreversible damage of the virus in liquid conditions (water) is observed using
stiff cantilevers (0.35 N m-1 ) and high A0 (81 nm), leading to a 6 nm reduction
in the height of TMV after the first scan. Finally, low values of the amplitude
set-point (A/A0 = 0.3), which means applying higher forces to the sample, also
brings the damage of TMV virus assemblies, reducing its monolayer roughness to
0.3 nm. Microsc. Res. Tech. 80:18-29, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27500683
TI - Complex Interaction Between Diphenylcyclopropenone and Immune Responses in
Alopecia Areata.
PMID- 27500684
TI - Renovation of Optically Active Phenanthrolines as Powerful Chiral Ligands for
Versatile Asymmetric Metal Catalysis.
AB - In the field of asymmetric synthesis, the development of new chiral ligands has
been regarded as an attractive challenge for decades. Novel chiral ligands can
often have a great impact on synthetic protocols. In this context, we are
currently interested in the application of 1,10-phenanthroline (phen) as an
entirely new class of chiral ligand. To handle this issue, we designed a chiral
phen ligand that provides the N,N,O-tridentate coordination of the phen moiety
and an additional phenolic hydroxyl group. As phen possesses greater coordination
ability with various ions, our chiral phen ligand would be valuable as one of the
"privileged" chiral ligands applied to a broad range of metal catalysts and new
reactions. This account summarizes the results of the application of the chiral
phen ligand to various kinds of metal catalysis.
PMID- 27500685
TI - An uncommon cause of erythema nodosum.
PMID- 27500686
TI - Steady-State Spectroscopic Analysis of Proton-Dependent Electron Transfer on
Pyrazine-Appended Metal Dithiolenes [Ni(pdt)2], [Pd(pdt)2], and [Pt(pdt)2] (pdt =
2,3-Pyrazinedithiol).
AB - We report the structural, electronic, and acid/base properties of a series of ML2
metal dithiolene complexes, where M = Ni, Pd, Pt and L = 2,3-pyrazinedithiol.
These complexes are non-innocent and possess strong electronic coupling between
ligands across the metal center. The electronic coupling can be readily
quantified in the monoanionic mixed valence state using Marcus-Hush theory.
Analysis of the intervalence charge transfer (IVCT) band reveals that that
electronic coupling in the mixed valence state is 5800, 4500, and 5700 cm(-1) for
the Ni, Pd, and Pt complexes, respectively. We then focus on their response to
acid titration in the mixed valence state, which generates the asymmetrically
protonated mixed valence mixed protonated state. For all three complexes,
protonation results in severe attenuation of the electronic coupling, as measured
by the IVCT band. We find nearly 5-fold decreases in electronic coupling for both
Ni and Pt, while, for the Pd complex, the electronic coupling is reduced to the
point that the IVCT band is no longer observable. We ascribe the reduction in
electronic coupling to charge pinning induced by asymmetric protonation. The more
severe reduction in coupling for the Pd complex is a result of greater energetic
mismatch between ligand and metal orbitals, reflected in the smaller electronic
coupling for the pure mixed valence state. This work demonstrates that the
bridging metal center can be used to tune the electronic coupling in both the
mixed valence and mixed valence mixed protonated states, as well as the magnitude
of change of the electronic coupling that accompanies changes in protonation
state.
PMID- 27500688
TI - Maternal uniparental disomy for chromosome 6 in a patient with IUGR, ambiguous
genitalia, and persistent mullerian structures.
AB - Maternal uniparental disomy of chromosome 6 [upd(6)mat] is rare and has only been
previously reported 13 times with the main associated phenotype being IUGR. We
present a case of a male patient with isodisomy upd(6)mat resulting in severe
IUGR and ambiguous genitalia, a phenotype not previously described in association
with this chromosome finding. The patient initially presented prenatally with
IUGR at 19 weeks gestation with placental dysfunction and ambiguous genitalia
noted at 27 weeks. Postnatally, the patient had external genital abnormalities,
the gonads were in the inguinal canal and there was a rudimentary appearing
vagina and uterus. Karyotype is 46, XY and SNP array revealed maternal isodisomy
of 171 Mb at 6p25.3q27 with no pathogenic copy number variants. To our best
knowledge, this is the first case of an XY patient with upd(6)mat with IUGR and
ambiguous genitalia, further supporting previous reports regarding an association
between upd(6)mat and IUGR. This patient also presented with a disorder of sex
development (46, XY DSD) with the sex chromosome being male and positive for the
SRY gene, testicular gonadal sex and abnormal external and internal genitalia.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27500687
TI - The functional effects of physical interactions involving cytochromes P450:
putative mechanisms of action and the extent of these effects in biological
membranes.
AB - Cytochromes P450 represent a family of enzymes, which are responsible for the
oxidative metabolism of a wide variety of xenobiotics. Although the mammalian
P450s require interactions with their redox partners in order to function, more
recently, P450 system proteins have been shown to exist as multi-protein
complexes that include the formation of P450*P450 complexes. Evidence has shown
that the metabolism of some substrates by a given P450 can be influenced by the
specific interaction of the enzyme with other forms of P450. Detailed kinetic
analysis of these reactions in vitro has shown that the P450-P450 interactions
can alter metabolism by changing the ability of a P450 to bind to its cognate
redox partner, NADPH-cytochrome P450 reductase; by altering substrate binding to
the affected P450; and/or by changing the rate of a catalytic step of the
reaction cycle. This review summarizes the known examples of P450-P450
interactions that have been shown in vitro to influence metabolism and
categorizes them according to the mechanism(s) causing the effects. P450-P450
interactions have the potential to cause major changes in the metabolism and
elimination of drugs in vivo. This review summarizes the evidence that the P450
P450 interactions influence metabolism in biological membranes and discusses the
studies, which will provide further insight into the extent of these effects in
the future.
PMID- 27500689
TI - "This is a question we have to ask everyone": asking young people about self-harm
and suicide.
AB - : WHAT IS KNOWN ON THE SUBJECT?: An essential part of the mental health
assessment is to evaluate the risk of harm to self. Fundamentally this involves
asking directly about self-harming behaviour and suicidal thoughts or urges, but
practitioners often find it difficult to open up these conversations. This
evaluation of risk is particularly important as self-harm and suicidal thoughts
are frequently found in young people who attend mental health services. WHAT THIS
PAPER ADDS TO EXISTING KNOWLEDGE?: Young people are not always routinely asked
directly about self-harm or suicidal thoughts when they are assessed. There are
two ways that mental health practitioners introduce this topic: first, by
building up to it by initially asking about general feelings, and second by
stating that it is a requirement to ask everyone. WHAT ARE THE IMPLICATIONS FOR
PRACTICE?: These questions should not be avoided by mental health practitioners
just because they are difficult. We offer suggestions as to how to ask questions
about self-harm and suicide based on real-world practice. ABSTRACT: Introduction
Questions about self-harm and suicide are essential in risk assessments with
children and young people, yet little is known about how mental health
practitioners do this. Aim The core aim was to examine how questions about self
harm and suicidal ideation are asked in real-world practice. Method A qualitative
design was employed to analyse 28 video-recorded naturally occurring mental
health assessments in a child and adolescent mental health service. Data were
analysed using conversation analysis (CA). Results In 13 cases young people were
asked about self-harm and suicide, but 15 were not. Analysis revealed how
practitioners asked these questions. Two main styles were revealed. First was an
incremental approach, beginning with inquiries about emotions and behaviours,
building to asking about self-harm and suicidal intent. Second was to externalize
the question as being required by outside agencies. Discussion The study
concluded that the design of risk questions to young people had implications for
how open they were to engaging with the practitioner. Implications for practice
The study has implications for training and practice for psychiatric nurses and
other mental health practitioners in feeling more confident in communicating with
young people about self-harm and suicidal ideation.
PMID- 27500690
TI - Individual, social and environmental predictors of regular exercise among adults
with type 2 diabetes and peripheral neuropathy in China.
AB - The purpose of the study was to explore the individual, social and environmental
factors influencing regular exercise on the basis of the theoretical framework of
social ecological model among adults with type 2 diabetes and peripheral
neuropathy. A total of 122 participants were chosen from Tianjin Metabolic
Disease Hospital from November 2013 to May 2014. Information on exercise status
and influencing factors was collected. Most participants took walking as the mode
of exercise and exercised alone. Only 59.8% of participants were reported to
carry out regular exercise. Logistic regression analysis suggested that being
male, longer duration with diabetic peripheral neuropathy, higher self-efficacy
for exercise and higher objective support were associated with regular exercise.
Exercise status was clearly not ideal among adults with type 2 diabetes and
peripheral neuropathy. The study highlighted the need to take measures to improve
self-efficacy for exercise and social support in order to promote exercise
participation among adults with type 2 diabetes and peripheral neuropathy.
PMID- 27500691
TI - Synthesis of novel lupane triterpenoid-indazolone hybrids with oxime ester
linkage.
AB - An efficient protocol for the synthesis of novel lupane triterpenoid-indazolone
hybrids with oxime ester linkage has been developed from naturally accessible
precursor betulin. For the first time a series of betulonic acid-indazolone
hybrids have been synthesized via an acylation of corresponding 6,7-dihydro-1H
indazol-4(5H)-one oximes with betulonic acid chloride. Diastereoselective
reduction of the obtained betulonic acid conjugates with NaBH4 resulted in a
formation of betulinic acid-indazolone hybrids in excellent yields. The
configuration of the key compounds has been fully established by X-ray and 2D NMR
analysis.
PMID- 27500692
TI - Glucocorticoid receptor-mediated insulin-like growth factor-I transcriptional
regulation in BeWo trophoblast cells before and after syncytialisation.
AB - Prenatal exposure to excessive glucocorticoids (GCs) leads to intrauterine growth
retardation and fetal programming of adult health and disease through
deregulation of placental functions. Placental secretion of insulin-like growth
factor-I (IGF-I) plays a critical role in the regulation of placental development
and function. However, it remains elusive whether GCs affect placental functions
through glucocorticoid receptor (GR)-mediated transcriptional regulation of IGF-I
gene. In this study, human placental choriocarcinoma (BeWo) cells before and
after syncytialization were used as cytotrophoblast and syncytiotrophoblast
models, respectively, to explore the effects of dexamethasone (Dex) on
transcriptional regulation of IGF-I gene at both stages. Dex significantly
inhibited (P<0.05) cell proliferation in cytotrophoblasts and down-regulated
amino acid transporter SLC7A5 in syncytiotrophoblasts. Concurrently, the
abundance of IGF-I mRNA and its transcript variants, together with IGF-I level in
culture media, were significantly reduced, in association with significantly
enhanced (P<0.05) GR phosphorylation. GR antagonist RU486 was able to abolish all
these effects. Two glucocorticoid response elements (GREs) were predicted in the
promoter regions of IGF-I gene. GR binding to GRE1 was significantly enriched
(P<0.05) in both cytotrophoblasts and syncytiotrophoblasts, but that to GRE2 was
significantly diminished (P<0.05) in cytotrophoblasts but not in
syncytiotrophoblasts, in response to Dex treatment. IGF-I supplementation
completely rescued Dex-induced cell cycle arrest but not SLC7A5 down-regulation,
indicating different regulatory mechanisms. Taken together, our results suggest
that GR-mediated transcriptional regulation of IGF-I is involved in Dex-induced
inhibition of placental cell proliferation and function.
PMID- 27500693
TI - Using Kotter's Change Model for Implementing Bedside Handoff: A Quality
Improvement Project.
PMID- 27500694
TI - Alarm Fatigue: Use of an Evidence-Based Alarm Management Strategy.
AB - The purpose of this article is to describe the impact of an evidence-based alarm
management strategy on patient safety. An alarm management program reduced alarms
up to 30%. Evaluation of patients on continuous cardiac monitoring showed a 3.5%
decrease in census. This alarm management strategy has the potential to save $136
500 and 841 hours of registered nurses' time per year. No patient harm occurred
during the 2-year project.
PMID- 27500695
TI - Nurse-Driven Protocol to Reduce Indwelling Catheter Dwell Time: A Health Care
Improvement Initiative.
PMID- 27500696
TI - Stopping the Slide: How Hospital Bed Design Can Minimize Active and Passive
Patient Migration.
AB - Patient migration, or the amount of movement toward the foot of the bed, has been
shown to significantly vary because of the mechanical design differences in
hospital beds. Previously, the amount of migration was measured immediately
following head-of-bed articulation in healthy subjects. This study not only
evaluates how much migration occurs immediately after head-of-bed articulation
but also measures additional migration during a standard 2-hour repositioning
period in subjects with limited mobility.
PMID- 27500697
TI - Improving Infusion Pump Safety Through Usability Testing.
AB - With the recognition that the introduction of new technology causes changes in
workflow and may introduce new errors to the system, usability testing was
performed to provide data on nursing practice and interaction with infusion pump
technology. Usability testing provides the opportunity to detect and analyze
potentially dangerous problems with the design of infusion pumps that could cause
or allow avoidable errors. This work will reduce preventable harm through the
optimization of health care delivery.
PMID- 27500698
TI - Development of Indicators to Measure Health Literate Discharge Practices.
AB - Health literate discharge practices meet the health literacy needs of patients
and families at the time of hospital discharge and are associated with improved
patient outcomes and reduced readmission. A Delphi panel consisting of nurses,
other health care providers, and researchers was used to develop a set of
indicators of health literate discharge practices based on the practices of
Project RED (Re-Engineered Discharge). These indicators can be used to measure
and monitor the use of health literate discharge practices.
PMID- 27500699
TI - Synthesis of Water-Soluble Deep-Cavity Cavitands.
AB - An efficient, four-step synthesis of a range of water-soluble, deep-cavity
cavitands is presented. Key to this approach are octahalide derivatives (4, X =
Cl or Br) that allow a range of water-solubilizing groups to be added to the
outer surface of the core host structure. In many cases, the conversion of the
starting dodecol (1) resorcinarene to the different cavitands avoids any
chromatographic procedures.
PMID- 27500700
TI - Chronic rhinosinusitis: the rationale for current treatments.
AB - INTRODUCTION: Chronic rhinosinusitis (CRS) is a broad clinical syndrome linked by
mucosal inflammation. Primary treatment modalities are corticosteroids and
antibiotics with surgery an option for failures, but the level of supporting
evidence is generally low. The primary reason is that CRS is a symptom complex
and not a specific disease. Areas covered: The primary treatment modalities for
CRS are corticosteroids, antibiotics and surgery. Corticosteroids, which have
very broad anti-inflammatory properties, also have the strongest evidence for
efficacy. Antibiotics are likely effective in a subpopulation of patients but the
various phenotypes and endotypes that make up CRS have thus far been poorly
defined. Early surgery as well as biologics may also be more efficacious and cost
effective in some phenotypes as well. Expert commentary: A better understanding
of the inflammatory pathways that drive CRS will permit investigators to separate
patient groups. This will allow for clinical trials that target specific
subpopulations and more personalized therapy for CRS patients in the future.
PMID- 27500701
TI - Psychoanalysis as a Philosophical Revolution: Freud's Divergence From the
Philosophy of Kant, Schopenhauer, and Nietzsche.
AB - In his classic, The Birth of Tragedy, Nietzsche described a philosophical
worldview that has many similarities to Freudian metapsychology. This paper uses
Freud's theories to analyze The Birth of Tragedy, discussing the similarities and
differences between Nietzsche's philosophy and Freudian metapsychology. The
author suggests that while psychoanalysis was born from the spirit of German
philosophy, in that it based itself on a similar concept of the unconscious,
Freud diverged from his predecessors to create a new worldview, based on the
acceptance and integration of unconscious desire. This revolutionary theory
provided a new approach to humanity's moral and existential issues.
PMID- 27500702
TI - Obsessive States: Aesthetics, Erotism, and Fantasy.
AB - Starting from his early writings, Freud devoted much thought to "obsessional
neurosis" and continued developing this theme for more than thirty years.
However, unlike the disorder hysteria, which in recent years has regained its
honorable status in psychoanalytic literature, obsessional neurosis has been
continually neglected and relegated to the fields of psychiatry and behavioral
psychology, which emphasize the symptomatic and the overt. This process, by
clinging to the objective aspects of obsessional neurosis and disassociating it
from the instincts and from its historical sources, may itself be deemed
obsessive. This paper suggests that obsessive processes should be viewed as
structuring a distinct psychic state pertinent to analysis even when obsessive
symptoms are not clearly present or apparent. Freud's conceptualizations thus
become more flexibly and widely applicable, allowing the analyst once again to
relate to the patient's inner world and to the original, implicit essence of
obsession, relying less significantly on what is outwardly apparent. The paper
will elaborate on three aspects of this "obsessive state": aesthetics, eroticism,
and fantasy. Finally, the value of the notion of obsessive psychic states will be
reassessed in the broader context of the role of sexuality in psychoanalytic
theory.
PMID- 27500703
TI - Zen Musings on Bion's "O" and "K".
AB - The author defines Bion's use of "O" and "K" and discusses both from the radical
nondualist realizational perspective available through the lens of Eihei Dogen's
(1200-1253) Soto Zen Buddhist orientation. Fundamental differences in core
foundational principles are discussed as well as similarities and their relevance
to clinical practice. A case example exemplifies and explicates the abstract
aspects of the discussion, which draws from Zen teaching stories, reference to
Dogen's original writings, and the scholarly commentarial literature as well as
from contemporary writers who integrate Zen Buddhist study and practice with
Bion's psychoanalytic writings on theory and technique.
PMID- 27500704
TI - Hermetic Narratives and False Analysis: A Unique Variant of the Mechanism of
Identification With the Aggressor.
AB - This paper focuses on a unique variant of the mechanism of identification with
the aggressor. The term "hermetic narrative" refers to a condition in which the
trauma victim creates a hermetically sealed narrative of witnessing, which
becomes an addictive and subjugating object in itself, while obstructing natural
processes of thinking. This paper examines the ways in which the hermetic
narrative reconstructs victim-aggressor relations both within the individual and
in the analytic relationship. It further discusses the risk of creating a "false
analysis" that is based on a malignant cooperation of the analyst and patient
with the internalized traumatic object.
PMID- 27500705
TI - Converging Paradigms: A Reflection on Parallel Theoretical Developments in
Psychoanalytic Metapsychology and Empirical Dream Research.
AB - In the last decades one can perceive a striking parallelism between the shifting
perspective of leading representatives of empirical dream research concerning
their conceptualization of dreaming and the paradigm shift within clinically
based psychoanalytic metapsychology with respect to its theory on the
significance of dreaming. In metapsychology, dreaming becomes more and more a
central metaphor of mental functioning in general. The theories of Klein, Bion,
and Matte-Blanco can be considered as milestones of this paradigm shift. In
empirical dream research, the competing theories of Hobson and of Solms
respectively argued for and against the meaningfulness of the dream-work in the
functioning of the mind. In the meantime, empirical data coming from various
sources seemed to prove the significance of dream consciousness for the
development and maintenance of adaptive waking consciousness. Metapsychological
speculations and hypotheses based on empirical research data seem to point in the
same direction, promising for contemporary psychoanalytic practice a more secure
theoretical base. In this paper the author brings together these diverse
theoretical developments and presents conclusions regarding psychoanalytic theory
and technique, as well as proposing an outline of an empirical research plan for
testing the specificity of psychoanalysis in developing dream formation.
PMID- 27500706
TI - Listening to and Sharing of Self in Psychoanalytic Supervision: The Supervisor's
Self-Perspective.
AB - Just as the analyst's self-perspective is critical to effective analytic process,
the supervisor's self-perspective is accordingly critical to effective
supervision process. But the supervisor's self-perspective has received virtually
no attention as a listening/experiencing perspective in the psychoanalytic
supervision literature. In this paper, the author defines the supervisor's self
perspective and considers five ways by which it contributes to an effective
supervisory process: (1) sharing one's own impressions of/reactions to patients;
(2) sharing personal disclosures about the supervisee-patient relationship; (3)
sharing personal disclosures about the supervisee as a developing analytic
therapist; (4) sharing personal disclosures about the supervisor-supervisee
relationship; and (5) using one's own self-reflection as a check and balance for
supervisory action. The supervisor's self-perspective provides the missing
supervisory voice in the triadic complement of subject-other-self, has the
potential to be eminently educative across the treatment/supervision dyads, and
serves as a prototype for the supervisee's own development and use of analytic
(or analyst) self-perspective.
PMID- 27500710
TI - Proton radiotherapy for gynecologic neoplasms.
AB - BACKGROUND: Proton beam therapy (PBT) is increasingly being used globally to
treat a variety of malignancies. This is the first review assessing PBT for
gynecologic neoplasms. Dose distribution to organs-at-risk (OARs), particularly
bone marrow (BM), is addressed. Clinical outcomes and toxicity data are detailed.
MATERIAL AND METHODS: Systematic searches of PubMed, EMBASE, abstracts from
meetings of the American Society for Radiation Oncology, Particle Therapy Co
Operative Group, and American Society of Clinical Oncology were conducted for
publications. There were no restrictions on publication dates. Sixteen original
investigations were identified and analyzed for this review. RESULTS: The
available evidence for PBT in treating gynecologic cancers is of both low
quantity and quality. The most studied scenarios for PBT include treatment of
para-aortic lymph nodes, re-irradiation, and as an alternative to brachytherapy,
and these also represent indications with the greatest opportunity for
demonstrating as yet unproven toxicity reductions. Dosimetric studies have shown
significantly decreased dose to OARs, such as the rectum, bladder, bowel,
kidneys, BM, and femoral heads. This dose reduction to OARs with PBT is more
pronounced within the low-dose volumes than the higher dose volumes, which
radiobiologically could be expected to lower second malignancy rates. Clinical
data, though no level 1 evidence, show appropriate stage-specific tumor control
and outcomes with PBT treatment, along with low toxicity rates. CONCLUSION: The
existing data, albeit limited, warrant and can help guide larger scale and higher
quality studies addressing whether PBT could provide clinically meaningful
differences in toxicities and outcomes in women with gynecologic neoplasms.
PMID- 27500711
TI - Single-Molecule Observation of a Mechanically Activated Cis-to-Trans Cyclopropane
Isomerization.
AB - The mechanochemical activation of cis-gem-difluorocyclopropane (cis-gDFC)
mechanophore in toluene was characterized with single-molecule force
spectroscopy. Unlike previously reported behavior in methyl benzoate (MB), two
transitions are observed in the force vs extension curves of cis-gDFC polymers in
toluene. The first transition occurs at the same force of ~1300 pN observed
previously in MB, but a second transition is observed at forces of ~1800 pN that
reveal the partial formation of the trans-gDFC isomer. The behavior is attributed
to competing reactions of the cis-gDFC at the 1300 pN plateau: addition of oxygen
to a ring-opened diradicaloid intermediate, and isomerization of cis-gDFC to its
trans isomer.
PMID- 27500709
TI - How multiple episodes of exclusive breastfeeding impact estimates of exclusive
breastfeeding duration: report from the eight-site MAL-ED birth cohort study.
AB - The duration of exclusive breastfeeding (EBF) is often defined as the time from
birth to the first non-breast milk food/liquid fed (EBFLONG), or it is estimated
by calculating the proportion of women at a given infant age who EBF in the
previous 24 h (EBFDHS). Others have measured the total days or personal
prevalence of EBF (EBFPREV), recognizing that although non-EBF days may occur,
EBF can be re-initiated for extended periods. We compared breastfeeding metrics
in the MAL-ED study; infants' breastfeeding trajectories were characterized from
enrollment (median 7 days, IQR: 4, 12) to 180 days at eight sites. During twice
weekly surveillance, caretakers were queried about infant feeding the prior day.
Overall, 101 833 visits and 356 764 child days of data were collected from 1957
infants. Median duration of EBFLONG was 33 days (95% CI: 32-36), compared to 49
days based on the EBFDHS. Median EBFPREV was 66 days (95% CI: 62-70). Differences
were because of the return to EBF after a non-EBF period. The median number of
returns to EBF was 2 (IQR: 1, 3). When mothers re-initiated EBF (second episode),
infants gained an additional 18.8 days (SD: 25.1) of EBF, and gained 13.7 days
(SD: 18.1) (third episode). In settings where women report short gaps in EBF,
programmes should work with women to return to EBF. Interventions could
positively influence the duration of these additional periods of EBF and their
quantification should be considered in impact evaluation studies. (c) 2016 John
Wiley & Sons Ltd.
PMID- 27500712
TI - Enhancement of the Initial Growth Rate of Agricultural Plants by Using Static
Magnetic Fields.
AB - Electronic devices and high-voltage wires induce magnetic fields. A magnetic
field of 1,300-2,500 Gauss (0.2 Tesla) was applied to Petri dishes containing
seeds of Garden Balsam (Impatiens balsamina), Mizuna (Brassica rapa var.
japonica), Komatsuna (Brassica rapa var. perviridis), and Mescluns (Lepidium
sativum). We applied magnets under the culture dish. During the 4 days of
application, we observed that the stem and root length increased. The group
subjected to magnetic field treatment (n = 10) showed a 1.4 times faster rate of
growth compared with the control group (n = 11) in a total of 8 days (p <0.0005).
This rate is 20% higher than that reported in previous studies. The tubulin
complex lines did not have connecting points, but connecting points occur upon
the application of magnets. This shows complete difference from the control,
which means abnormal arrangements. However, the exact cause remains unclear.
These results of growth enhancement of applying magnets suggest that it is
possible to enhance the growth rate, increase productivity, or control the speed
of germination of plants by applying static magnetic fields. Also, magnetic
fields can cause physiological changes in plant cells and can induce growth.
Therefore, stimulation with a magnetic field can have possible effects that are
similar to those of chemical fertilizers, which means that the use of fertilizers
can be avoided.
PMID- 27500713
TI - Improved Insulin Pharmacokinetics Using a Novel Microneedle Device for
Intradermal Delivery in Patients with Type 2 Diabetes.
AB - BACKGROUND: Currently available short-acting insulin analogs have slower
absorption compared with endogenous insulin occasionally resulting in immediate
postprandial hyperglycemia. Intradermal (ID) injection facilitates faster drug
absorption and may result in improved insulin pharmacokinetics. METHODS:
Seventeen patients with type 2 diabetes were included in this single-center,
pilot, open-label crossover study. Patients received 0.2 U/kg Insulin aspart ID
injections using a MicronJet (MJ) needle and subcutaneous (SC) injections, using
a conventional needle in a crossover design. Thirteen patients were studied under
fasting conditions and four before a standard meal test. The
pharmacokinetic/pharmacodynamic (PK/PD) profile, as well as the safety and
tolerability of injections, was compared. RESULTS: Fourteen patients completed
the study per-protocol. ID versus SC injection demonstrated significantly shorter
Tmax (median 35 vs. 87.5 min [P < 0.001]), while the Cmax did not significantly
differ (median 80 vs. 55 MUU/mL [P = 0.085]). Median insulin area under the curve
(AUC; 360 min) did not differ between the groups (9914 vs. 10,936 MUU/mL/min [p =
0.077]), yet 0-60 min insulin AUC was higher with ID versus SC injection (mean +/
SD 3821 +/- 1429 vs. 2534 +/- 737 MUU/mL/min [p = 0.01]) and 4-6 h AUC was lower
with ID versus SC injection (mean +/- SD 2054 +/- 858 vs. 2929 +/- 1412
MUU/mL/min [p = 0.02]). The relative bioavailability of the ID versus the SC
insulin (AUCID/AUCSC) was similar (median 0.91 [95% confidence interval 0.73
1.27]). CONCLUSIONS: ID insulin injection delivered through an MJ needle
demonstrated superior PK profile compared with conventional SC administration,
including shorter Tmax and higher early and lower late exposure in patients with
type 2 diabetes. This may help achieve better insulin coverage of meals and lower
postprandial glucose excursions.
PMID- 27500714
TI - RAMA casein zymography: Time-saving and highly sensitive casein zymography for
MMP7 and trypsin.
AB - To detect metalloproteinase-7 (MMP7), zymography is conducted using a casein
substrate and conventional CBB stain. It has disadvantages because it is time
consuming and has low sensitivity. Previously, a sensitive method to detect MMP7
up to 30 pg was reported, however it required special substrates and complicated
handlings. RAMA casein zymography described herein is rapid, sensitive, and
reproducible. By applying high-sensitivity staining with low substrate
conditions, the staining process is completed within 1 h and sensitivity was
increased 100-fold. The method can detect 10 pg MMP7 by using commercially
available casein without complicated handlings. Moreover, it increases detection
sensitivity for trypsin.
PMID- 27500715
TI - Treatment of Medial Collateral Ligament Injuries of the Elbow with Use of the
"Tommy John" Operation: Indications and Results.
PMID- 27500716
TI - Total Hip Replacement with Use of a Direct Anterior Approach: A Critical Analysis
Review.
PMID- 27500717
TI - Has the Promise Been Kept?
PMID- 27500718
TI - Recombinant Human Bone Morphogenetic Protein-2 in Spine Surgery.
PMID- 27500719
TI - Radiographic and Scintigraphic Evaluation of Bone Tumors and Diseases.
PMID- 27500720
TI - A High-content In Vitro Pancreatic Islet beta-cell Replication Discovery
Platform.
AB - Loss of insulin-producing beta-cells is a central feature of diabetes. While a
variety of potential replacement therapies are being explored, expansion of
endogenous insulin-producing pancreatic islet beta-cells remains an attractive
strategy. beta-cells have limited spontaneous regenerative activity;
consequently, a crucial research effort is to develop a precise understanding of
the molecular pathways that restrain beta-cell growth and to identify drugs
capable of overcoming these restraints. Herein an automated high-content image
based primary-cell screening method to identify beta-cell replication-promoting
small molecules is presented. Several, limitations of prior methodologies are
surmounted. First, use of primary islet cells rather than an immortalized cell
line maximizes retention of in vivo growth restraints. Second, use of mixed
composition islet-cell cultures rather than a beta-cell-line allows
identification of both lineage-restricted and general growth stimulators. Third,
the technique makes practical the use of primary islets, a limiting resource,
through use of a 384-well format. Fourth, detrimental experimental variability
associated with erratic islet culture quality is overcome through optimization of
isolation, dispersion, plating and culture parameters. Fifth, the difficulties of
accurately and consistently measuring the low basal replication rate of islet
endocrine-cells are surmounted with optimized immunostaining parameters,
automated data acquisition and data analysis; automation simultaneously enhances
throughput and limits experimenter bias. Notable limitations of this assay are
the use of dispersed islet cultures which disrupts islet architecture, the use of
rodent rather than human islets and the inherent limitations of throughput and
cost associated with the use of primary cells. Importantly, the strategy is
easily adapted for human islet replication studies. This assay is well suited for
investigating the mitogenic effect of substances on beta-cells and the molecular
mechanisms that regulate beta-cell growth.
PMID- 27500721
TI - Refractory Status Epilepticus in Children: Intention to Treat With Continuous
Infusions of Midazolam and Pentobarbital.
AB - OBJECTIVE: To describe pediatric patients with convulsive refractory status
epilepticus in whom there is intention to use an IV anesthetic for seizure
control. DESIGN: Two-year prospective observational study evaluating patients
(age range, 1 mo to 21 yr) with refractory status epilepticus not responding to
two antiepileptic drug classes and treated with continuous infusion of anesthetic
agent. SETTING: Nine pediatric hospitals in the United States. PATIENTS: In a
cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr;
50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. MAIN
RESULTS: The median (interquartile range) ICU length of stay was 10 (3-20) days.
Up to four "cycles" of serial anesthetic therapy were used, and seizure
termination was achieved in 94% by the second cycle. Seizure duration in
controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a
second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most
frequent first-line anesthetic agent (78%); pentobarbital was the most frequently
used second-line agent after midazolam failure (82%). An electroencephalographic
endpoint was used in over half of the patients; higher midazolam dosing was used
with a burst suppression endpoint. In midazolam nonresponders, transition to a
second agent occurred after a median of 1 day. Most patients (94%) experienced
seizure termination with these two therapies. CONCLUSIONS: Midazolam and
pentobarbital remain the mainstay of continuous infusion therapy for refractory
status epilepticus in the pediatric patient. The majority of patients experience
seizure termination within a median of 30 hours. These data have implications for
the design and feasibility of future intervention trials. That is, testing a new
anesthetic anticonvulsant after failure of both midazolam and pentobarbital is
unlikely to be feasible in a pediatric study, whereas a decision to test an
alternative to pentobarbital, after midazolam failure, may be possible in a
multicenter multinational study.
PMID- 27500722
TI - Treatment of Pediatric Septic Shock With the Surviving Sepsis Campaign Guidelines
and PICU Patient Outcomes.
AB - OBJECTIVES: The Surviving Sepsis Campaign recommends rapid recognition and
treatment of severe sepsis and septic shock. Few reports have evaluated the
impact of these recommendations in pediatrics. We sought to determine if outcomes
in patients who received initial care compliant with the Surviving Sepsis
Campaign time goals differed from those treated more slowly. DESIGN: Single
center retrospective cohort study. SETTING: Emergency department and PICU at an
academic children's hospital. PATIENTS: Three hundred twenty-one patients treated
for septic shock in the emergency department and admitted directly to the PICU.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure was receipt of
emergency department care compliant with the Surviving Sepsis Campaign
recommendations (delivery of IV fluids, IV antibiotics, and vasoactive infusions
within 1 hr of shock recognition). The primary outcome was development of new or
progressive multiple organ dysfunction syndrome. Secondary outcomes included
mortality, need for mechanical ventilation or vasoactive medications, and
hospital and PICU length of stay. Of the 321 children studied, 117 received
Surviving Sepsis Campaign compliant care in the emergency department and 204 did
not. New or progressive multiple organ dysfunction syndrome developed in nine of
the patients (7.7%) who received Surviving Sepsis Campaign compliant care and 25
(12.3%) who did not (p = 0.26). There were 17 deaths; overall mortality rate was
5%. There were no significant differences between groups in any of the secondary
outcomes. Although only 36% of patients met the Surviving Sepsis Campaign
guideline recommendation of bundled care within 1 hour of shock recognition, 75%
of patients received the recommended interventions in less than 3 hours.
CONCLUSIONS: Treatment for pediatric septic shock in compliance with the
Surviving Sepsis Campaign recommendations was not associated with better outcomes
compared with children whose initial therapies in the emergency department were
administered more slowly. However, all patients were treated rapidly and we
report low morbidity and mortality. This underscores the importance of rapid
recognition and treatment of septic shock.
PMID- 27500723
TI - Inotropic Therapy in Newborns, A Population-Based National Registry Study.
AB - OBJECTIVE: To describe the use of inotropic drugs and the characteristics of
neonates receiving such treatment in a national cohort of patients admitted to
neonatal ICUs in Norway. DESIGN: A national registry study of patients included
in the Norwegian Neonatal Network database 2009-2014. Demographic and treatment
data, including the use of inotropic drugs (dopamine, dobutamine, epinephrine,
norepinephrine, milrinone, and levosimendan) and outcomes, were retrieved and
analyzed. SETTING: Neonatal ICUs in Norway. PATIENTS: All patients admitted to
Norwegian neonatal ICUs 2009-2014 with a postmenstrual age of less than 310 days
at admission, corresponding to a postnatal age of less than 28 days for a child
born at term (n = 36 397). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
Inotropic drugs were administered to 974 of 361,803 live born infants (0.27%) in
the study period, representing 2.7% of the neonatal ICU patient population. The
relative proportion of neonatal ICU patients receiving inotropes decreased with
increasing gestational age, yet 41% of the patients receiving inotropes were born
at term. Of note, 89.8% of treated patients received dopamine. Use of inotropes
was particularly prevalent in patients with necrotizing enterocolitis (72.4%) and
pulmonary hypertension (42.1%) and in patients with gestational age less than 28
weeks (28.2%). Inotropic treatment initiated in the first week of life (84.2%)
was associated with birth asphyxia and pulmonary hypertension, whereas treatment
initiated after the first week of life was associated with extremely preterm
birth, neonatal surgery, neonatal sepsis, cardiac disease, and necrotizing
enterocolitis. CONCLUSIONS: This comprehensive epidemiologic study indicates that
less than 0.3% of newborns receive inotropic support in the neonatal period.
Dopamine was the most commonly used drug. Relating inotrope use to clinical
condition, gestational age, and postnatal age may be useful for clinicians and
helpful in delineating relevant patient populations for future clinical trials.
PMID- 27500724
TI - Defective proviruses rapidly accumulate during acute HIV-1 infection.
AB - Although antiretroviral therapy (ART) suppresses viral replication to clinically
undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in
CD4(+) T cells in a latent form that is not targeted by the immune system or by
ART. This latent reservoir is a major barrier to curing individuals of HIV-1
infection. Many individuals initiate ART during chronic infection, and in this
setting, most proviruses are defective. However, the dynamics of the accumulation
and the persistence of defective proviruses during acute HIV-1 infection are
largely unknown. Here we show that defective proviruses accumulate rapidly within
the first few weeks of infection to make up over 93% of all proviruses,
regardless of how early ART is initiated. By using an unbiased method to amplify
near-full-length proviral genomes from HIV-1-infected adults treated at different
stages of infection, we demonstrate that early initiation of ART limits the size
of the reservoir but does not profoundly affect the proviral landscape. This
analysis allows us to revise our understanding of the composition of proviral
populations and estimate the true reservoir size in individuals who were treated
early versus late in infection. Additionally, we demonstrate that common assays
for measuring the reservoir do not correlate with reservoir size, as determined
by the number of genetically intact proviruses. These findings reveal hurdles
that must be overcome to successfully analyze future HIV-1 cure strategies.
PMID- 27500727
TI - Human Placental and Decidual Organ Cultures to Study Infections at the Maternal
fetal Interface.
AB - The placenta shows a large degree of interspecies anatomic variability. To best
understand biology and pathophysiology of the human placenta, it is imperative to
design experiments using human cells and tissues. An advantage of organ culture
is maintenance of three-dimensional (3D) structural organization and
extracellular matrix. The goal of the method described here is successful
establishment of ex vivo human gestational tissue organ cultures and their
healthy culture maintenance for 72-96 hr. The protocol details the immediate
processing of research-consented, placental and decidual specimens fresh from the
operating suite. These are abundant specimens that would otherwise be discarded.
Detailed instructions on the sterile collection of these samples, including
morphologic details on how to select appropriate tissues to establish 3D organ
cultures, is provided. Placental villous and decidual tissues are microdissected
into 2-3 mm(3) pieces and placed separately on matrix-lined transwell filters and
cultured for several days. Villous and decidual organ cultures are well suited
for the study of human host-pathogen interaction. As compared to other model
organisms, these human cultures are particularly advantageous to examine
mechanism of infection for pathogens that demonstrate variable patterns of host
specificity. As an example, we demonstrate infection of placental and decidual
organ cultures with the clinically relevant, facultative intracellular bacterial
pathogen Listeria monocytogenes.
PMID- 27500726
TI - Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF
inhibition in melanoma.
AB - The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an
oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi)
have shown high response rates and extended survival in patients with melanoma
who bear tumors that express mutations encoding BRAF proteins mutant at Val600,
but a vast majority of these patients develop drug resistance. Here we show that
loss of stromal antigen 2 (STAG2) or STAG3, which encode subunits of the cohesin
complex, in melanoma cells results in resistance to BRAFi. We identified loss-of
function mutations in STAG2, as well as decreased expression of STAG2 or STAG3
proteins in several tumor samples from patients with acquired resistance to BRAFi
and in BRAFi-resistant melanoma cell lines. Knockdown of STAG2 or STAG3
expression decreased sensitivity of BRAF(Val600Glu)-mutant melanoma cells and
xenograft tumors to BRAFi. Loss of STAG2 inhibited CCCTC-binding-factor-mediated
expression of dual specificity phosphatase 6 (DUSP6), leading to reactivation of
mitogen-activated protein kinase (MAPK) signaling (via the MAPKs ERK1 and ERK2;
hereafter referred to as ERK). Our studies unveil a previously unknown genetic
mechanism of BRAFi resistance and provide new insights into the tumor suppressor
function of STAG2 and STAG3.
PMID- 27500725
TI - Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in
patients with systemic lupus erythematosus.
AB - Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune
disease characterized by altered balance of activity between effector and
regulatory CD4(+) T cells. The homeostasis of CD4(+) T cell subsets is regulated
by interleukin (IL)-2, and reduced production of IL-2 by T cells is observed in
individuals with SLE. Here we report that treatment with low-dose recombinant
human IL-2 selectively modulated the abundance of regulatory T (Treg) cells,
follicular helper T (TFH) cells and IL-17-producing helper T (TH17) cells, but
not TH1 or TH2 cells, accompanied by marked reductions of disease activity in
patients with SLE.
PMID- 27500728
TI - Nanoengineering a library of metallic nanostructures using a single microfluidic
reactor.
AB - Microfluidic synthesis in a microfabricated reactor enables fast and facile
synthesis of a wide library of metallic nanostructures: monometallic, bimetallic,
anisotropic growth and heterostructures. Specific nanostructures are realized by
selection of flow pattern and synthesis parameters. The technique is shown to
have advantages over conventional batch technologies. Not only does it allow
faster scalable synthesis, but also realization of nanostructures hitherto not
reported such as Pt-Ru, Pt-Ni and Pt-Co nanodendrites, Pt-Pd heterostructures, Ag
Pd core-shell NPs, Au-Pd nanodumbbells and Au-Pd nanosheets.
PMID- 27500729
TI - Development of a Colloidal Gold-based Immunochromatographic Test Strip for
Detection of Cetacean Myoglobin.
AB - This protocol describes the development of a colloidal gold immunochromatographic
test strip based on the sandwich format that can be used to differentiate the
myoglobin (Mb) of cetaceans from that of seals and other animals. The strip
provides rapid and on-the-spot screening for cetacean meat, thereby restraining
its illegal trade and consumption. Two monoclonal antibodies (mAbs) with
reactivity toward the Mb of cetaceans were developed. The amino acid sequences of
Mb antigenic reactive regions from various animals were analyzed in order to
design two synthetic peptides (a general peptide and a specific peptide) and
thereafter raise the mAbs (subclass IgG1). The mAbs were selected from hybridomas
screened by indirect ELISA, western blot and dot blot. CGF5H9 was specific to the
Mbs of rabbits, dogs, pigs, cows, goats, and cetaceans while it showed weak to no
affinity to the Mbs of chickens, tuna and seals. CSF1H13 can bind seals and
cetaceans with strong affinity but showed no affinity to other animals. Cetacean
samples from four families (Balaenopteridae, Delphinidae, Phocoenidae and
Kogiidae) were used in this study, and the results indicated that these two mAbs
have broad binding ability to Mbs from different cetaceans. These mAbs were
applied on a sandwich-type colloidal gold immunochromatographic test strip.
CGF5H9, which recognizes many species, was colloid gold-labeled and used as the
detection antibody. CSF1H13, which was coated on the test zone, detected the
presence of cetacean and seal Mbs. Muscle samples from tuna, chicken, seal, five
species of terrestrial mammals and 15 species of cetaceans were tested in
triplicate. All cetacean samples showed positive results and all the other
samples showed negative results.
PMID- 27500730
TI - Effect of Feed Form and Whole Grain Feeding on Gastrointestinal Weight and the
Prevalence of Campylobacter jejuni in Broilers Orally Infected.
AB - Two independent trials were carried out to evaluate the effect of feed form,
whole wheat (WW) and oat hulls (OH) addition on gastrointestinal (GIT) weight and
Campylobacter jejuni colonization in orally infected birds. In Trial 1, there
were six treatments factorially arranged with two feed forms (mash vs pellets),
and three levels of WW from 1-21/22-42d: 0/0, 7.5/15%, 15/30%. Broilers were
allocated in cages (3 birds/cage, 12 cages/treatment). In Trial 2, there were
three treatments: a mash diet, a mash diet including WW (7.5% from 1-21 and 15%
from 22-42d), and a third treatment including also 5%OH. Broilers were allocated
in floor pens (1 pen with 30 birds/treatment). At 14d, all broilers in Trial 1 or
3 broilers/pen in Trial 2 were orally challenged with 1.5 x 105 cfu of C. jejuni
ST-45 /. In Trial 1, birds fed pelleted diets consumed 13.5% more feed, gained
31% more weight, and presented 12.9% better feed conversion for the whole trial
(P<0.05). Pelleting decreased the relative weight of GIT and gizzard and
increased the relative weight of proventriculus (P<0.05). Mash diets decreased pH
in the gizzard (P<0.05). Inclusion of WW decreased the relative weight of
proventriculus, increased gizzard weight, and reduced pH in the gizzard (P<0.05).
At 21d of age, mash tended to reduce C. jejuni compared to pellets (7.85 vs 8.27
log10cfu/g; P = 0.091) and WW inclusion at 7.5/15% reduced C. jejuni colonization
when compared to lower and higher inclusion (P<0.05). In Trial 2, birds fed T3
(WW+OH) showed 1.38 log10cfu/g less than birds fed Control diet (P<0.05). In
conclusion, despite of the clear morphological changes in the GIT derived of FF
and WW inclusion, no clear reductions in C. jejuni populations in the ceca were
observed. However, WW and OH inclusion to mash diets significantly reduced cecal
C. jejuni colonization at 42 days.
PMID- 27500731
TI - Transgenic Suppression of AGAMOUS Genes in Apple Reduces Fertility and Increases
Floral Attractiveness.
AB - We investigated the ability of RNA interference (RNAi) directed against two co
orthologs of AGAMOUS (AG) from Malus domestica (domestic apple, MdAG) to reduce
the risks of invasiveness and provide genetic containment of transgenes, while
also promoting the attractiveness of flowers for ornamental usage. Suppression of
two MdAG-like genes, MdMADS15 and MdMADS22, led to the production of trees with
highly showy, polypetalous flowers. These "double-flowers" had strongly reduced
expression of both MdAG-like genes. Members of the two other clades within in the
MdAG subfamily showed mild to moderate differences in gene expression, or were
unchanged, with the level of suppression approximately proportional to the level
of sequence identity between the gene analyzed and the RNAi fragment. The double
flowers also exhibited reduced male and female fertility, had few viable pollen
grains, a decreased number of stigmas, and produced few viable seeds after cross
pollination. Despite these floral alterations, RNAi-AG trees with double-flowers
set full-sized fruit. Suppression or mutation of apple AG-like genes appears to
be a promising method for combining genetic containment with improved floral
attractiveness.
PMID- 27500732
TI - Analysis of the Enantioselective Effects of PCB95 in Zebrafish (Danio rerio)
Embryos through Targeted Metabolomics by UPLC-MS/MS.
AB - As persistent organic pollutants, polychlorinated biphenyls (PCBs) accumulate in
the bodies of animals and humans, resulting in toxic effects on the reproductive,
immune, nervous, and endocrine systems. The biological and toxicological
characteristics of enantiomers of chiral PCBs may differ, but these
enantioselective effects of PCBs have not been fully characterized. In this
study, we performed metabolomics analysis, using ultra-high performance liquid
chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the
enantioselective toxic effects of PCB95 in zebrafish (Danio rerio) embryos after
exposure to three dose levels of 0.1, 1, and 10 MUg/L for 72 h. Multivariate
analysis directly reflected the metabolic perturbations caused by PCB95. The
effects of (-)-PCB95 and (+)-PCB95 were more prominent than those of the racemate
in zebrafish embryos. A total of 26 endogenous metabolites were selected as
potential marker metabolites with variable importance at projection values larger
than 1 and significant differences (p<0.05). These metabolites included amino
acids, organic acids, nucleosides, betaine, and choline. The changes in these
biomarkers were dependent on the enantiomer-specific structures of PCB95. Fifteen
metabolic pathways were significantly affected, and several nervous and immune
system-related metabolites were significantly validated after exposure. These
metabolic changes indicated that the toxic effects of PCB95 may be associated
with the interaction of PCB95 with the nervous and immune systems, thus resulting
in disruption of energy metabolism and liver function.
PMID- 27500733
TI - Disposition and Pharmacokinetics of a GalNAc3-Conjugated Antisense
Oligonucleotide Targeting Human Lipoprotein (a) in Monkeys.
AB - Triantennary N-acetyl galactosamine (GalNAc3)-conjugated antisense
oligonucleotides (ASOs) have greatly improved potency due to receptor-mediated
uptake into hepatocyte. The disposition and pharmacokinetics of ISIS 681257, a
GalNAc3-conjugated ASO, were studied in monkeys. Following subcutaneous (SC)
injection, ISIS 681257 was rapidly absorbed into the systemic circulation, with
peak plasma levels observed within hours after dosing. After reaching Cmax,
plasma concentrations rapidly declined in a multiexponential manner and were
characterized by a dominant initial rapid distribution phase in which drug
transferred to tissues from circulation, followed by a much slower terminal
elimination phase (half-life of 4 weeks). Intact ISIS 681257 is the major full
length oligonucleotide species in plasma (>=70%). In tissues, the conjugated
GalNAc sugar moiety was rapidly metabolized, leaving the fully unconjugated form
as the only full-length oligonucleotide detected at 48 h after dosing.
Unconjugated ISIS 681257 cleared slowly from tissues with a half-life of 4 weeks.
ISIS 681257 was highly bound to plasma proteins (>97% bound), which limited its
urinary excretion. Disposition of ISIS 681257 in plasma and liver appeared
nonlinear over the 1-40 mg/kg dose range studied. The plasma and liver tissue
concentration data were well described by a population based mixed-effects
modeling approach with Michaelis-Menten uptake from plasma to liver. Safety data
from the study and the good exposure, as well as the extended half-life of the
unconjugated ASO in the liver, support further development and less frequent
dosing in Phase I clinical study.
PMID- 27500734
TI - Potential beneficial impact of angiotensin receptor blockers on arterial
stiffness in hypertension.
PMID- 27500735
TI - Brucella melitensis Methionyl-tRNA-Synthetase (MetRS), a Potential Drug Target
for Brucellosis.
AB - We investigated Brucella melitensis methionyl-tRNA-synthetase (BmMetRS) with
molecular, structural and phenotypic methods to learn if BmMetRS is a promising
target for brucellosis drug development. Recombinant BmMetRS was expressed,
purified from wild type Brucella melitensis biovar Abortus 2308 strain ATCC/CRP
#DD-156 and screened by a thermal melt assay against a focused library of one
hundred previously classified methionyl-tRNA-synthetase inhibitors of the blood
stage form of Trypanosoma brucei. Three compounds showed appreciable shift of
denaturation temperature and were selected for further studies on inhibition of
the recombinant enzyme activity and cell viability against wild type B.
melitensis strain 16M. BmMetRS protein complexed with these three inhibitors
resolved into three-dimensional crystal structures and was analyzed. All three
selected methionyl-tRNA-synthetase compounds inhibit recombinant BmMetRS
enzymatic functions in an aminoacylation assay at varying concentrations.
Furthermore, growth inhibition of B. melitensis strain 16M by the compounds was
shown. Inhibitor-BmMetRS crystal structure models were used to illustrate the
molecular basis of the enzyme inhibition. Our current data suggests that BmMetRS
is a promising target for brucellosis drug development. However, further studies
are needed to optimize lead compound potency, efficacy and safety as well as
determine the pharmacokinetics, optimal dosage, and duration for effective
treatment.
PMID- 27500736
TI - Riemerella anatipestifer M949_1360 Gene Functions on the Lipopolysaccharide
Biosynthesis and Bacterial Virulence.
AB - Riemerella anatipestifer causes septicemic and exudative diseases in poultry,
resulting in major economic losses to the duck industry. Lipopolysaccharide
(LPS), as an important virulence factor in Gram-negative bacteria, can be
recognized by the immune system and plays a crucial role in many interactions
between bacteria and animal hosts. In this study, we screened out one LPS
defective mutant strain RADelta604 from a random transposon mutant library of R.
anatipestifer serotype 1 strain CH3, which did not react with the anti-CH3 LPS
monoclonal antibody 1C1 in an indirect enzyme-linked immunosorbent assay.
Southern blot analysis confirmed that the genome of RADelta604 contained a single
Tn4351 insert. Then, we found that the M949_1360 gene was inactivated by
insertion of the transposon. Using silver staining and western blot analyses, we
found that the LPS pattern of RADelta604 was defective, as compared with that of
the wild-type (WT) strain CH3. The mutant strain RADelta604 showed no significant
influence on bacterial growth, while bacterial counting and Live/dead BacLight
Bacterial Viability staining revealed that bacterial viability was decreased, as
compared with the WT strain CH3. In addition, the abilities of the mutant strain
RADelta604 to adhere and invade Vero cells were significantly decreased. Animal
studies revealed that the virulence of the mutant strain RADelta604 was decreased
by more than 200-fold in a duck infection model, as compared with the WT strain
CH3. Furthermore, immunization with live bacteria of the mutant strain RADelta604
protected 87.5% ducks from challenge with R. anatipestifer serotype 1 strain WJ4,
indicating that the mutant strain RADelta604 could be used as a potential vaccine
candidate in the future.
PMID- 27500737
TI - The Mechanism for Type I Interferon Induction by Mycobacterium tuberculosis is
Bacterial Strain-Dependent.
AB - Type I interferons (including IFNalphabeta) are innate cytokines that may
contribute to pathogenesis during Mycobacterium tuberculosis (Mtb) infection. To
induce IFNbeta, Mtb must gain access to the host cytosol and trigger stimulator
of interferon genes (STING) signaling. A recently proposed model suggests that
Mtb triggers STING signaling through bacterial DNA binding cyclic GMP-AMP
synthase (cGAS) in the cytosol. The aim of this study was to test the
generalizability of this model using phylogenetically distinct strains of the Mtb
complex (MTBC). We infected bone marrow derived macrophages with strains from
MTBC Lineages 2, 4 and 6. We found that the Lineage 6 strain induced less
IFNbeta, and that the Lineage 2 strain induced more IFNbeta, than the Lineage 4
strain. The strains did not differ in their access to the host cytosol and
IFNbeta induction by each strain required both STING and cGAS. We also found that
the three strains shed similar amounts of bacterial DNA. Interestingly, we found
that the Lineage 6 strain was associated with less mitochondrial stress and less
mitochondrial DNA (mtDNA) in the cytosol compared with the Lineage 4 strain.
Treating macrophages with a mitochondria-specific antioxidant reduced cytosolic
mtDNA and inhibited IFNbeta induction by the Lineage 2 and 4 strains. We also
found that the Lineage 2 strain did not induce more mitochondrial stress than the
Lineage 4 strain, suggesting that additional pathways contribute to higher
IFNbeta induction. These results indicate that the mechanism for IFNbeta by Mtb
is more complex than the established model suggests. We show that mitochondrial
dynamics and mtDNA contribute to IFNbeta induction by Mtb. Moreover, we show that
the contribution of mtDNA to the IFNbeta response varies by MTBC strain and that
additional mechanisms exist for Mtb to induce IFNbeta.
PMID- 27500739
TI - No recommendation of routine perioperative statin use for prevention of acute
kidney injury in patients undergoing cardiac surgery.
PMID- 27500740
TI - Microfluidic Pneumatic Cages: A Novel Approach for In-chip Crystal Trapping,
Manipulation and Controlled Chemical Treatment.
AB - The precise localization and controlled chemical treatment of structures on a
surface are significant challenges for common laboratory technologies. Herein, we
introduce a microfluidic-based technology, employing a double-layer microfluidic
device, which can trap and localize in situ and ex situ synthesized structures on
microfluidic channel surfaces. Crucially, we show how such a device can be used
to conduct controlled chemical reactions onto on-chip trapped structures and we
demonstrate how the synthetic pathway of a crystalline molecular material and its
positioning inside a microfluidic channel can be precisely modified with this
technology. This approach provides new opportunities for the controlled assembly
of structures on surface and for their subsequent treatment.
PMID- 27500738
TI - Drosophila Spidey/Kar Regulates Oenocyte Growth via PI3-Kinase Signaling.
AB - Cell growth and proliferation depend upon many different aspects of lipid
metabolism. One key signaling pathway that is utilized in many different anabolic
contexts involves Phosphatidylinositide 3-kinase (PI3K) and its membrane lipid
products, the Phosphatidylinositol (3,4,5)-trisphosphates. It remains unclear,
however, which other branches of lipid metabolism interact with the PI3K
signaling pathway. Here, we focus on specialized fat metabolizing cells in
Drosophila called larval oenocytes. In the presence of dietary nutrients,
oenocytes undergo PI3K-dependent cell growth and contain very few lipid droplets.
In contrast, during starvation, oenocytes decrease PI3K signaling, shut down cell
growth and accumulate abundant lipid droplets. We now show that PI3K in larval
oenocytes, but not in fat body cells, functions to suppress lipid droplet
accumulation. Several enzymes of fatty acid, triglyceride and hydrocarbon
metabolism are required in oenocytes primarily for lipid droplet induction rather
than for cell growth. In contrast, a very long chain fatty-acyl-CoA reductase
(FarO) and a putative lipid dehydrogenase/reductase (Spidey, also known as Kar)
not only promote lipid droplet induction but also inhibit oenocyte growth. In the
case of Spidey/Kar, we show that the growth suppression mechanism involves
inhibition of the PI3K signaling pathway upstream of Akt activity. Together, the
findings in this study show how Spidey/Kar and FarO regulate the balance between
the cell growth and lipid storage of larval oenocytes.
PMID- 27500741
TI - An azaspirane derivative suppresses growth and induces apoptosis of ER-positive
and ER-negative breast cancer cells through the modulation of JAK2/STAT3
signaling pathway.
AB - Persistent activation of signal transducer and activator of transcription 3
(STAT3) is associated with the progression of a range of tumors. In this report,
we present the anticancer activity of 2-(1-(4-(2-cyanophenyl)1-benzyl-1H-indol-3
yl)-5-(4-methoxy-phenyl)-1-oxa-3-azaspiro(5,5)undecane (CIMO) against breast
cancer cells. We observed that CIMO suppresses the proliferation of both estrogen
receptor-negative (ER-) (BT-549, MDA-MB-231) and estrogen receptor-positive (ER+)
(MCF-7, and BT-474) breast cancer (BC) cells with IC50 of 3.05, 3.41, 4.12 and
4.19 uM, respectively, and without significantly affecting the viability of
normal cells. CIMO was observed to mediate its anti-proliferative effect in ER-
BC cells by inhibiting the phosphorylation of JAK2 and STAT3 proteins.
Quantitative PCR analysis demonstrated that CIMO decreases the relative mRNA
expression of genes that are involved in cell cycle progression (CCND1) and cell
survival (BCL2, BCL-xL, BAD, CASP 3/7/9, and TP53). In addition, CIMO was
observed to arrest BC cells at G0/G1 phase and of the cell cycle. Furthermore,
CIMO suppressed BC cell migration and invasion with concordant regulation of
genes involved in epithelial to mesechymal transition (CDH1, CDH2, OCLN and VIM).
Thus, we report the utility of a synthetic azaspirane which targets the JAK-STAT
pathway in ER- BC.
PMID- 27500742
TI - Fast imaging of laboratory core floods using 3D compressed sensing RARE MRI.
AB - Three-dimensional (3D) imaging of the fluid distributions within the rock is
essential to enable the unambiguous interpretation of core flooding data.
Magnetic resonance imaging (MRI) has been widely used to image fluid saturation
in rock cores; however, conventional acquisition strategies are typically too
slow to capture the dynamic nature of the displacement processes that are of
interest. Using Compressed Sensing (CS), it is possible to reconstruct a near
perfect image from significantly fewer measurements than was previously thought
necessary, and this can result in a significant reduction in the image
acquisition times. In the present study, a method using the Rapid Acquisition
with Relaxation Enhancement (RARE) pulse sequence with CS to provide 3D images of
the fluid saturation in rock core samples during laboratory core floods is
demonstrated. An objective method using image quality metrics for the
determination of the most suitable regularisation functional to be used in the CS
reconstructions is reported. It is shown that for the present application, Total
Variation outperforms the Haar and Daubechies3 wavelet families in terms of the
agreement of their respective CS reconstructions with a fully-sampled reference
image. Using the CS-RARE approach, 3D images of the fluid saturation in the rock
core have been acquired in 16min. The CS-RARE technique has been applied to image
the residual water saturation in the rock during a water-water displacement core
flood. With a flow rate corresponding to an interstitial velocity of vi=1.89+/
0.03ftday(-1), 0.1 pore volumes were injected over the course of each image
acquisition, a four-fold reduction when compared to a fully-sampled RARE
acquisition. Finally, the 3D CS-RARE technique has been used to image the
drainage of dodecane into the water-saturated rock in which the dynamics of the
coalescence of discrete clusters of the non-wetting phase are clearly observed.
The enhancement in the temporal resolution that has been achieved using the CS
RARE approach enables dynamic transport processes pertinent to laboratory core
floods to be investigated in 3D on a time-scale and with a spatial resolution
that, until now, has not been possible.
PMID- 27500743
TI - Comment on "Surgically Resected Gall Bladder: Is Histopathology Needed for All?".
PMID- 27500744
TI - Toward Accurate Modeling of the Effect of Ion-Pair Formation on Solute Redox
Potential.
AB - A scheme to model the dependence of a solute redox potential on the supporting
electrolyte is proposed, and the results are compared to experimental
observations and other reported theoretical models. An improved agreement with
experiment is exhibited if the effect of the supporting electrolyte on the redox
potential is modeled through a concentration change induced via ion pair
formation with the salt, rather than by only considering the direct impact on the
redox potential of the solute itself. To exemplify the approach, the scheme is
applied to the concentration-dependent redox potential of select molecules
proposed for nonaqueous flow batteries. However, the methodology is general and
enables rational computational electrolyte design through tuning of the operating
window of electrochemical systems by shifting the redox potential of its solutes;
including potentially both salts as well as redox active molecules.
PMID- 27500745
TI - Teaching to the test: developing an assessment tool for novice
echocardiographers.
PMID- 27500746
TI - Nucleophilic Difluoromethylenation of Ketones Using Diethyl
(Difluoro(trimethylsilyl)methyl)phosphonate Mediated by 18-Crown-6 Ether/KOAc.
AB - We report a general difluoromethylenation of various types of ketones using
diethyl (difluoro(trimethylsilyl)methyl)phosphonate mediated by the combination
of 18-crown-6 and KOAc. It provides facile access to structurally diverse beta
hydroxy-alpha,alpha-difluorophosphonates as interesting targets for medicinal
research.
PMID- 27500747
TI - Significance of groundwater flux on contaminant concentration and mass discharge
in the nonaqueous phase liquid (NAPL) contaminated zone.
AB - Groundwater flowing through residual nonaqueous phase liquid (NAPL) source zone
will cause NAPL dissolution and generate large contaminant plume. The use of
contaminant mass discharge (CMD) measurements in addition to NAPL aqueous phase
concentration to characterize site conditions and assess remediation performance
is becoming popular. In this study, we developed new and generic numerical models
to investigate the significance of groundwater flux temporal variations on the
NAPL source dynamics. The developed models can accommodate any temporal
variations of groundwater flux in the source zone. We examined the various
features of groundwater flux using a few selected functional forms of linear
increase/decrease, gradual smooth increase/decrease, and periodic fluctuations
with a general trend. Groundwater flux temporal variations have more pronounced
effects on the contaminant mass discharge dynamics than the aqueous
concentration. If the groundwater flux initially increases, then the reduction in
contaminant mass discharge (CMDR) vs. NAPL mass reduction (MR) relationship is
mainly downward concave. If the groundwater flux initially decreases, then CMDR
vs. MR relationship is mainly upward convex. If the groundwater flux variations
are periodic, the CMDR vs. MR relationship tends to also have periodic variations
ranging from upward convex to downward concave. Eventually, however, the CMDR vs.
MR relationship approaches 1:1 when majority of the NAPL mass becomes depleted.
PMID- 27500748
TI - Groundwater contamination in coastal urban areas: Anthropogenic pressure and
natural attenuation processes. Example of Recife (PE State, NE Brazil).
AB - In a context of increasing land use pressure (over-exploitation, surface-water
contamination) and repeated droughts, identifying the processes affecting
groundwater quality in coastal megacities of the tropical and arid countries will
condition their long-term social and environmental sustainability. The present
study focuses on the Brazilian Recife Metropolitan Region (RMR), which is a
highly urbanized area (3,743,854 inhabitants in 2010) on the Atlantic coast
located next to an estuarial zone and overlying a multi-layered sedimentary
system featured by a variable sediment texture and organic content. It
investigates the contamination and redox status patterns conditioning potential
attenuation within the shallow aquifers that constitute the interface between the
city and the strategic deeper semi-confined aquifers. These latter are
increasingly exploited, leading to high drawdown in potenciometric levels of 20
30m and up to 70m in some high well density places, and potentially connected to
the surface through leakage. From a multi-tracer approach (major ions, major
gases, delta(11)B, delta(18)O-SO4, delta(34)S-SO4) carried out during two field
campaigns in September 2012 and March 2013 (sampling of 19 wells and 3 surface
waters), it has been possible to assess the contamination sources and the redox
processes. The increasing trend for mineralization from inland to coastal and
estuarial wells (from 119 to around 10,000MUS/cm) is at first attributed to water
rock interactions combined with natural and human-induced potentiometric
gradients. Secondly, along with this trend, one finds an environmental pressure
gradient related to sewage and/or surface-channel network impacts (typically
depleted delta(11)B within the range of 10-150/00) that are purveyors of
chloride, nitrate, ammonium and sulfate. Nitrate, ammonium and sulfate (ranging
from 0 to 1.70mmol/L, from 0 to 0,65mmol/L, from 0.03 to 3.91mmol/L respectively
are also potentially produced or consumed through various redox processes (pyrite
oxidation, denitrification, dissimilatory nitrate reduction to ammonium) within
the system, as is apparent within a patchwork of biogeochemical reactors.
Furthermore, intensive pumping in the coastal area with its high well density
punctually leads to temporary well salinization ([Cl] reaching temporarily
79mmol/L). Our results, summarized as a conceptual scheme based on environmental
conditions, is a suitable basis for implementing sustainable management in
coastal sedimentary hydrosystems influenced by highly urbanized conditions.
PMID- 27500749
TI - Effects of reservoir heterogeneity on scaling of effective mass transfer
coefficient for solute transport.
AB - Modeling transport process at large scale requires proper scale-up of subsurface
heterogeneity and an understanding of its interaction with the underlying
transport mechanisms. A technique based on volume averaging is applied to
quantitatively assess the scaling characteristics of effective mass transfer
coefficient in heterogeneous reservoir models. The effective mass transfer
coefficient represents the combined contribution from diffusion and dispersion to
the transport of non-reactive solute particles within a fluid phase. Although
treatment of transport problems with the volume averaging technique has been
published in the past, application to geological systems exhibiting realistic
spatial variability remains a challenge. Previously, the authors developed a new
procedure where results from a fine-scale numerical flow simulation reflecting
the full physics of the transport process albeit over a sub-volume of the
reservoir are integrated with the volume averaging technique to provide effective
description of transport properties. The procedure is extended such that spatial
averaging is performed at the local-heterogeneity scale. In this paper, the
transport of a passive (non-reactive) solute is simulated on multiple reservoir
models exhibiting different patterns of heterogeneities, and the scaling behavior
of effective mass transfer coefficient (Keff) is examined and compared. One such
set of models exhibit power-law (fractal) characteristics, and the variability of
dispersion and Keff with scale is in good agreement with analytical expressions
described in the literature. This work offers an insight into the impacts of
heterogeneity on the scaling of effective transport parameters. A key finding is
that spatial heterogeneity models with similar univariate and bivariate
statistics may exhibit different scaling characteristics because of the influence
of higher order statistics. More mixing is observed in the channelized models
with higher-order continuity. It reinforces the notion that the flow response is
influenced by the higher-order statistical description of heterogeneity. An
important implication is that when scaling-up transport response from lab-scale
results to the field scale, it is necessary to account for the scale-up of
heterogeneity. Since the characteristics of higher-order multivariate
distributions and large-scale heterogeneity are typically not captured in small
scale experiments, a reservoir modeling framework that captures the uncertainty
in heterogeneity description should be adopted.
PMID- 27500750
TI - Dipeptide-Based Carbohydrate Receptors and Polymers for Glycopeptide Enrichment
and Glycan Discrimination.
AB - Glycoproteomics identifies and catalogs protein glycosylation and explores its
impact on protein conformations and biofunctions. However, these studies are
restricted by the bottleneck to enrich low-abundance glycopeptides from complex
biosamples and the difficulties in analyzing glycan structures by mass
spectrometry. Here, we report dipeptide as a simple but promising carbohydrate
binding platform to tackle these problems. We build a hydropathy-index-based
strategy for sequence optimization and screen out three optimal dipeptide
sequences from 54 types of dipeptides. The optimized dipeptide-based homopolymers
display excellent performance (e.g., selectivity up to ~70% for real biosamples
and strong anti-interference capacity capable of resisting 1000-fold bovine serum
albumin interference) in glycopeptide enrichment. Meanwhile, our polymers exhibit
high-efficiency chromatographic separation toward oligosaccharides with different
compositions, polymerization degrees and even their linkage isomers. This brings
another attractive feature that our materials can discriminate subtly variable
glycan structures of glycopeptides, especially, isomeric glycosidic linkages.
These features provide a solid foundation to analyze the complex glycan
structures and glycosites simultaneously, which will benefit future development
of glycoproteomics and glycobiology.
PMID- 27500751
TI - Stability analysis of switched cellular neural networks: A mode-dependent average
dwell time approach.
AB - This paper addresses the exponential stability of switched cellular neural
networks by using the mode-dependent average dwell time (MDADT) approach. This
method is quite different from the traditional average dwell time (ADT) method in
permitting each subsystem to have its own average dwell time. Detailed
investigations have been carried out for two cases. One is that all subsystems
are stable and the other is that stable subsystems coexist with unstable
subsystems. By employing Lyapunov functionals, linear matrix inequalities (LMIs),
Jessen-type inequality, Wirtinger-based inequality, reciprocally convex approach,
we derived some novel and less conservative conditions on exponential stability
of the networks. Comparing to ADT, the proposed MDADT show that the minimal dwell
time of each subsystem is smaller and the switched system stabilizes faster. The
obtained results extend and improve some existing ones. Moreover, the validness
and effectiveness of these results are demonstrated through numerical
simulations.
PMID- 27500752
TI - Long-Term Outcomes and Complications of Intracardiac Echocardiography-Assisted
Patent Foramen Ovale Closure in 1,000 Consecutive Patients.
AB - BACKGROUNDS: Long-term fate of patients submitted to patent foramen ovale (PFO)
closure is still unclear. The aim of the study was to evaluate the incidence of
atrial fibrillation (AF), aortic or atrial free wall erosion, device thrombosis
(DT), new onset or worsening of mitral valve regurgitation (MVR), and recurrent
cerebral ischemic events in the long-term follow up after intracardiac
echocardiography (ICE)-aided PFO closure in a large population. METHODS: We
reviewed the medical and instrumental data of 1,000 consecutive patients (mean
age 47.3 +/- 17.1 years, females) prospectively enrolled in 2 centres over a 13
years period (February 1999-February 2012) for R-to-L shunt ICE-aided catheter
based closure using different devices. RESULTS: Immediate success was 99.8%.
Implanted devices were Amplatzer PFO Occluder in 463 patients (46.3%), Amplatzer
ASD Cribriform Occluder in 420 patients (42.0%), Premere Occlusion System in 95
patients (9.5%), and Biostar Occluder in 22 patients (2.2%). On a mean follow-up
of 12.3 +/- 0.6 years (minimum 4- maximum 17 years), permanent AF occurred in
0.5%, DT was apparent in 0.5%, new onset or worsening of MVR was observed in
0.2%, whereas recurrent cerebral ischemic events were 0.8%. Occlusion rate was
93.8%. No aortic or atrial free wall erosion has been observed. CONCLUSION: ICE
aided closure of PFO using different devices, appeared very safe and effective on
very long-term follow up with low incidence of erosion, DT, recurrent ischemic
events, MVR new onset or worsening, and permanent AF.
PMID- 27500753
TI - Use of antibiotics is associated with lower enterolactone plasma concentration.
AB - SCOPE: High enterolactone levels may have health benefits in relation to risk of
noncommunicable diseases. Enterolactone is produced by the colonic microbiota
after intake of lignans and treatment with antimicrobials may result in altered
enterolactone production. This study investigates the association between
antibiotic use and enterolactone concentration. METHODS AND RESULTS: Using LC
MS/MS, enterolactone concentrations were quantified in plasma samples from 2237
participants from the Diet, Cancer and Health cohort. The participants were
healthy at enrollment, but were later diagnosed with cancer. At enrollment,
participants had blood drawn and completed a food frequency questionnaire and
lifestyle questionnaire. Antibiotic use was assessed as reimbursed antibiotic
prescriptions up to 12 months before enrollment. Antibiotic use <=3 months before
enrollment was associated with a 41% (Deltacrude : -41; 95% CI: -52, -28) lower
enterolactone concentration in women and 12% in men (Deltacrude : -12; 95% CI:
31, 11), while antibiotic use >3-12 months before enrollment was associated with
26% lower enterolactone in women (Deltacrude : -26; 95% CI: -37, -14) and 14% in
men (Deltacrude : -14; 95% CI: -28, 1). CONCLUSION: Use of antibiotics up to 12
months before enrollment was associated with lower plasma enterolactone levels,
especially among women.
PMID- 27500754
TI - Does intraspecific behavioural variation of pollinator species influence
pollination? A quantitative study with hummingbirds and a Neotropical shrub.
AB - Floral visitors differ in their efficacy as pollinators, and the impact of
different pollinator species on pollen flow and plant reproduction has been
frequently evaluated. In contrast, the impact of intraspecific behavioural
changes on their efficacy as pollinators has seldom been quantified. We studied a
self-incompatible shrub Palicourea rigida (Rubiaceae) and its hummingbird
pollinators, which adjust their behaviour according to floral resource
availability. Fluorescence microscopy was used to access pollen tube growth and
incompatibility reaction in pistils after a single visit of territorial or
intruder hummingbirds in two populations. To characterise the plant populations
and possible differences in resource availability between areas we used a three
term quadrat variance method to detect clusters of floral resources. Within
species variation in foraging behaviour, but not species identity, affected
pollinator efficacy. Effectively, hummingbirds intruding into territories
deposited more compatible pollen grains on P. rigida stigmas than territory
holders in both study areas. Additionally, territory holders deposited more
incompatible than compatible pollen grains. Our results imply that intraspecific
foraging behaviour variation has consequences for pollination success.
Quantifying such variation and addressing the implications of intraspecific
variability contribute to a better understanding of the dynamics and consequences
of plant-pollinator interactions.
PMID- 27500755
TI - Relationship between smoking and adverse outcomes in patients with atrial
fibrillation: A meta-analysis and systematic review.
AB - BACKGROUND: Several studies have investigated the impact of smoking on the
prognosis of atrial fibrillation (AF), but the results remain controversial. We
therefore aimed to estimate the association between smoking and adverse outcomes
in patients with AF. METHODS: We systematically searched the Cochrane Library,
PubMed, and Elsevier databases through May 2016 for studies regarding the
association between smoking and adverse outcomes in AF patients. Risk ratios
[RRs] and 95% confidence intervals [CIs] were abstracted and then pooled using a
random-effects model. RESULTS: A total of 8 cohort studies with 87,373
participants were included in this meta-analysis. Among patients with AF, smoking
was associated with increased risks of all-cause death (RR=1.82, 95% CI: 1.33
2.49, P=0.0002) and cardiovascular death (RR=1.54, 95% CI: 1.31-1.81, P<0.00001)
but not stroke/thromboembolism (RR=1.19, 95% CI 0.97-1.46; P=0.10). In addition,
smoking was associated with an increased risk of major bleeding (RR=1.93, 95% CI
1.08-3.47, P=0.03), even after adjustment for the antithrombotic treatment.
CONCLUSIONS: The published literature demonstrates that smoking is not associated
with the risk of stroke/thromboembolism but increases the risks of all-cause
death and cardiovascular death in AF patients, as well as the risk of major
bleeding in AF patients using anticoagulants.
PMID- 27500756
TI - Marital status and living condition as predictors of mortality and readmissions
among African Americans with heart failure.
AB - Socioeconomic factors, including social support, may partially explain why
African Americans (AA) have the highest prevalence of heart failure and with
worse outcomes compared to other races. AA are more likely to be hospitalized and
readmitted for heart failure and have higher mortality. The purpose of this study
is to determine whether the social factors of marital status and living condition
affect readmission rates and all-cause mortality following hospitalization for
acute decompensated heart failure (ADHF) in AA patients. METHODS: Medical records
from 611 AA admitted to Einstein Medical Center Philadelphia from January, 2011
to February, 2013 for ADHF were reviewed. Patient demographics including living
condition (nursing home residents, living with family or living alone) and
marital status (married or non-married -including single, divorced, separated and
widowed) were correlated with all-cause mortality and readmission rates. RESULTS:
In this cohort (53% male, mean age 65+/-15, mean ejection fraction 32+/-16%) 25%
(n=152) of subjects were unmarried. Unmarried patients had significantly higher
30-day readmission rates (16% vs. 6% p=0.0002) and higher 1-year mortality (17%
vs. 11% p=0.047) compared with married patients. Fifty percent (n=303) of
subjects were living with family members, while 40% (n=242) and 11% (n=66) were
living alone or in a nursing facility, respectively. Patients living with family
members had significantly lower 30-day readmission rates when compared with those
living alone or in a nursing facility (7% vs 21% vs. 18% p=<0.0001). Furthermore,
they had the lowest 1-year mortality (14% vs 32% for nursing facility patients
and 17% for those living alone (p=0.0007). After controlling for traditional risk
factors (age, gender, body mass index, peak troponin I, left ventricular ejection
fraction, B-type natriuretic peptide, hypertension, diabetes mellitus,
hyperlipidemia, and coronary artery disease), being married was an indpendent
predictor of 1-year mortality (OR 0.50 p=0.019) and living alone for 30-day
readmission (OR 2.86 p=<0.001). CONCLUSION: The socioeconomic factors of marital
status and living condition significantly correlated with mortality and 30-day
readmission rate in AA heart failure patients. Specifically, being married and
living with family independently predict lower mortality and fewer readmissions.
Surprisingly, living in a nursing facility was associated with significantly
higher mortality than living alone or with family.
PMID- 27500757
TI - Retrograde revascularization of ostial left main CTO using internal mammary
artery byepass graft: A case report.
PMID- 27500758
TI - Acupuncture for heart failure: A systematic review of clinical studies.
AB - BACKGROUND: Acupuncture has been used for treating heart failure mainly in
combination with conventional treatments, but evidence for its effectiveness and
safety has not been well established. Our aim was to review randomized controlled
trials (RCTs) on acupuncture for heart failure and assess the clinical evidence.
METHODS: Electronic databases such as Medline, EMBASE, Cochrane Central Register
of Controlled Trials (CENTRAL) and certain Chinese & Korean databases were
searched until October 2015. The main outcomes assessed were mortality, New York
Heart Association (NYHA) function classifications, and acupuncture-related
adverse events. The details of acupuncture intervention were also investigated.
RESULTS: Among 4107 publications, seven RCTs were included; most of them showed
considerable methodological flaws. We could not conduct a meta-analysis because
of the heterogeneity of the included studies. In one acute heart failure study,
acupuncture shortened intensive care unit (ICU) stay by 2.2days (95% CI 1.26,
3.14) and reduced the risk ratio of re-admission to 0.53 (95% CI 0.28, 0.99).
However, mortality was not affected. Hemodynamic parameters also showed
improvement. Another study reported an improved left ventricular ejection
fraction by 9.95% (95% CI 3.24, 16.66). In five chronic heart failure studies,
acupuncture improved exercise capacity, quality of life, hemodynamic parameters,
and time domain heart rate variability parameters. Acupuncture decreased NT-pro
BNP levels by 292.20 (95% CI -567.36, -17.04). No adverse effects were reported.
CONCLUSIONS: The effectiveness of acupuncture as a therapy for heart failure is
currently inconclusive. Further large and rigorous clinical trials are needed to
establish its clinical utility.
PMID- 27500759
TI - Endovascular anatomic reconstruction of the iliac bifurcation with covered
stentgrafts in sandwich-technique for the treatment of complex aorto-iliac
aneurysms.
AB - OBJECTIVE: Endovascular anatomic reconstruction of iliac artery bifurcation in
aorto-iliac aneurysms using commercial stentgrafts in sandwich-technique by
bilateral transfemoral approach. METHODS: 24 patients (mean 73.8+/-standard
deviation 6.8years) with complex aorto-iliac aneurysms (AAA): n=17; diameter 64+/
15 [48-100]mm; common-iliac-artery (CIA): n=27; 43+/-15 [30-87]mm; internal-iliac
artery (IIA): n=14; 28+/-8 [15-43]mm) were prospectively enrolled for EVAR with
preservation of the IIA (n=31; bi-lateral n=7). Maintenance of antegrade flow to
IIA by iliac reconstruction was performed in sandwich-technique prior to EVAR.
Follow-up of 15.0+/-10.8 [1-40]months included contrast-enhanced ultrasound and
computed-tomography after 1week, 3, 6 and every 12months. RESULTS: Initial
technical success for anatomic reconstruction of the iliac arteries in 31
instances was 100%. Primary patency of iliac neo-bifurcations was 90.9% (20/22)
at 6months and 84.2% (16/19) at 1year. Postprocedural gutter-endoleaks type 1b
were obvious in 6.5% (2/31) of cases, which disappeared 3months later.
Aortic/iliac aneurysm-size after 1year decreased (>5mm) in 61.5% of patients. No
aneurysm-size increase or late rupture occurred. CONCLUSIONS: Endovascular
reconstruction of the iliac bifurcation with commercial standard stentgrafts is
safe and effective. Transfemoral approach allows extension of distal landing zone
for EVAR while preserving the internal iliac artery blood-flow, even in
unfavorable iliac anatomy.
PMID- 27500760
TI - Expanding the functional role of miRNAs in the establishment of permanent atrial
fibrillation.
PMID- 27500761
TI - Elevated fibroblast growth factor-23 and risk of cardiovascular disease or
mortality in the general population: A meta-analysis.
PMID- 27500762
TI - Pre-test probability of obstructive coronary stenosis in patients undergoing
coronary CT angiography: Comparative performance of the modified diamond
Forrester algorithm versus methods incorporating cardiovascular risk factors.
AB - BACKGROUND: Current guidelines recommend the use of the Modified Diamond
Forrester (MDF) method to assess the pre-test likelihood of obstructive coronary
artery disease (CAD). We aimed to compare the performance of the MDF method with
two contemporary algorithms derived from multicenter trials that additionally
incorporate cardiovascular risk factors: the calculator-based 'CAD Consortium 2'
method, and the integer-based CONFIRM score. METHODS: We assessed 1069
consecutive patients without known CAD undergoing coronary CT angiography (CCTA)
for stable chest pain. Obstructive CAD was defined as the presence of coronary
stenosis >=50% on 64-slice dual-source CT. The three methods were assessed for
calibration, discrimination, net reclassification, and changes in proposed
downstream testing based upon calculated pre-test likelihoods. RESULTS: The
observed prevalence of obstructive CAD was 13.8% (n=147). Overestimations of the
likelihood of obstructive CAD were 140.1%, 9.8%, and 18.8%, respectively, for the
MDF, CAD Consortium 2 and CONFIRM methods. The CAD Consortium 2 showed greater
discriminative power than the MDF method, with a C-statistic of 0.73 vs. 0.70
(p<0.001), while the CONFIRM score did not (C-statistic 0.71, p=0.492).
Reclassification of pre-test likelihood using the 'CAD Consortium 2' or CONFIRM
scores resulted in a net reclassification improvement of 0.19 and 0.18,
respectively, which would change the diagnostic strategy in approximately half of
the patients. CONCLUSIONS: Newer risk factor-encompassing models allow for a more
precise estimation of pre-test probabilities of obstructive CAD than the
guideline-recommended MDF method. Adoption of these scores may improve disease
prediction and change the diagnostic pathway in a significant proportion of
patients.
PMID- 27500763
TI - Comparative safety and effectiveness of coronary computed tomography: Systematic
review and meta-analysis including 11 randomized controlled trials and 19,957
patients.
AB - BACKGROUND/OBJECTIVES: The clinical approach to suspected or established coronary
artery disease (CAD) has been revolutionized in the last few decades by coronary
computed tomography (coroCT). Yet, uncertainty persists on its comparative
diagnostic and clinical effectiveness. We conducted a systematic review on
randomized controlled trials (RCTs) of coroCT. METHODS: We searched RCTs in
PubMed and The Cochrane Library, extracting as outcomes of interest long-term
rates of death, myocardial infarction, revascularization, and invasive coronary
angiography. Effects were estimated with risk ratios (RR) and 95% confidence
intervals. RESULTS: A total of 11 trials were included, with 19,957 patients
followed for a median of 6months. One trial focused on screening, 3 on stable
CAD, and 7 on acute CAD. Meta-analysis showed that coroCT was associated with a
trend toward fewer deaths or myocardial infarctions (RR=0.84 [0.70-1.01]) whereas
no significant difference was found for the risk of death (RR=0.91 [0.71-1.18]).
Conversely, the risk of myocardial infarction tended to be lower with coroCT at
the overall analysis (RR=0.77 [0.59-1.02]), and this effect reached statistical
significance in studies focusing on subjects with stable CAD (RR=0.69 [0.49
0.99]). These potential benefits were offset (or mediated) by a significant
albeit modest increase in the need for invasive angiography (RR=1.36 [1.08
1.72]), and ensuing coronary revascularization (RR=1.76 [1.29-2.40]).
CONCLUSIONS: According to the current evidence base, coroCT is associated with an
increased usage of invasive angiography and coronary revascularization when
compared to standard of care, with possible benefits on nonfatal myocardial
infarction, but without significant benefits on death or the composite of death
or myocardial infarction.
PMID- 27500764
TI - A case of false positive cardiac troponin I in CANOMAD syndrome.
PMID- 27500765
TI - Apelin-13 infusion salvages the peri-infarct region to preserve cardiac function
after severe myocardial injury.
AB - BACKGROUND: Apelin-13 (A13) regulates cardiac homeostasis. However, the effects
and mechanism of A13 infusion after an acute myocardial injury (AMI) have not
been elucidated. This study assesses the restorative effects and mechanism of A13
on the peri-infarct region in murine AMI model. METHODS: 51 FVB/N mice (12weeks,
30g) underwent AMI. A week following injury, continuous micro-pump infusion of
A13 (0.5MUg/g/day) and saline was initiated for 4-week duration. Dual contrast
MRI was conducted on weeks 1, 2, 3, and 5, consisting of delayed-enhanced and
manganese-enhanced MRI. Four mice in each group were followed for an extended
period of 4weeks without further infusion and underwent MRI scans on weeks 7 and
9. RESULTS: A13 infusion demonstrated preserved LVEF compared to saline from
weeks 1 to 4 (21.9+/-3.2% to 23.1+/-1.7%* vs. 23.5+/-1.7% to 16.9+/-2.8%,
*p=0.02), which persisted up to 9weeks post-MI (+1.4%* vs. -9.4%, *p=0.03).
Mechanistically, dual contrast MRI demonstrated significant decrease in the peri
infarct and scar % volume in A13 group from weeks 1 to 4 (15.1 to 7.4% and 34.3
to 25.1%, p=0.02, respectively). This was corroborated by significant increase in
5-ethynyl-2'-deoxyuridine (EdU(+)) cells by A13 vs. saline groups in the peri
infarct region (16.5+/-3.1% vs. 8.1+/-1.6%; p=0.04), suggesting active cell
mitosis. Finally, significantly enhanced mobilization of CD34(+) cells in the
peripheral blood and up-regulation of APJ, fibrotic, and apoptotic genes in the
peri-infarct region were found. CONCLUSIONS: A13 preserves cardiac performance by
salvaging the peri-infarct region and may contribute to permanent restoration of
the severely injured myocardium.
PMID- 27500766
TI - Elevated levels of plasma transforming growth factor-beta1 in idiopathic and
heritable pulmonary arterial hypertension.
AB - BACKGROUND: Aberrant transforming growth factor (TGF)-beta signaling is involved
in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to
investigate the predictive value of the upstream ligand of TGF-beta signaling
(TGF-beta1) on long-term mortality and the clinical characteristics of patients
with idiopathic pulmonary arterial hypertension (IPAH) and heritable PAH (HPAH).
METHODS AND RESULTS: Plasma TGF-beta1 levels were measured in 151 IPAH and 65
HPAH patients retrospectively enrolled between January 2008 and March 2013, and
compared to 61 healthy subjects. Data for mortality over time were obtained from
hospital databases and from telephone follow-ups. The main outcome was all-cause
death. Plasma TGF-beta1 was significantly higher in IPAH/HPAH patients compared
to control subjects (4.74 vs. 2.61ng/mL, respectively; P<0.001). Mean follow-up
time was 3.4+/-1.8years, during which 86 patients died. ROC curves were utilized
to determine TGF-beta1 cutoff values. Compared to patients with TGF-beta1 of
<3.74ng/mL, heart function was significantly impaired (percentage of patients
with WHO functional class III/IV, 51.4% vs. 65.5%, P=0.043) and mortality risk
was elevated (P=0.009) for patients with TGF-beta1>3.74ng/mL. However, the
difference in mortality rate between patients with higher and lower TGF-beta1
levels was only statistically significant for female patients (P=0.004), despite
a similar trend for male patients. Multivariate analyses revealed that TGF-beta1
(HR after log transformation base of 10: 2.623; 95%CI: 1.228-5.603; P=0.013)
emerged as the independent predictor for all-cause mortality. CONCLUSION: High
circulating levels of TGF-beta1 were an independent predictor of a poor outcome
for IPAH/HPAH patients.
PMID- 27500767
TI - The Difference between the optical coherence tomography (OCT) findings of newly
progressed coronary lesions in symptomatic and asymptomatic patients.
AB - BACKGROUND: Generally, newly progressed coronary lesions (NPCLs) are considered
to be composed of lipid-rich plaques. In case of vulnerable plaque rupture, they
may quickly become culprit lesions responsible for acute coronary syndromes.
METHODS: Between September 2011 and September 2015, 2034 patients underwent
scheduled follow-up coronary angiography (CAG) after percutaneous coronary
intervention (PCI) in Tsuchiya General Hospital. Patients with NPCLs found by CAG
during the follow-up period were evaluated by optical coherence tomography (OCT).
NPCLs were defined as the lesions with less than 50% diameter stenosis, which
progressed to more than 75% diameter stenosis within 3years after the previous
CAG. Patients with restenosis after PCI were excluded. We compared OCT findings
of NPCLs between symptomatic and asymptomatic patients. RESULTS: The follow-up
CAG showed NPCLs in 64 patients (3.2%). OCT revealed fibrous plaque in 42
patients (65.6%) and thin-cap fibroatheroma in one patient. Thirteen patients had
chest symptoms for one month before CAG and the remaining 51 patients were
asymptomatic. The prevalence of fibrous plaque and intimal disruption or plaque
rupture were not significantly different between symptomatic and asymptomatic
patients (61.5% vs. 66.7%, p=0.752 and 30.8% vs. 11.8%, p=0.213, respectively).
However, thrombi were more frequently observed in symptomatic patients (61.5% vs.
13.7%, p<0.001). CONCLUSIONS: The majority of NPCLs found in asymptomatic
patients at follow-up CAG were not vulnerable; however, those found in
symptomatic patients might be vulnerable. In clinical practice, NPCLs found in
asymptomatic patients should be evaluated for functional severity of stenosis in
order to determine the need for coronary revascularization.
PMID- 27500768
TI - Compensated Ferrimagnetic Tetragonal Heusler Thin Films for Antiferromagnetic
Spintronics.
AB - Fully compensated ferrimagnets with tetragonal crystal structure have the
potential for large spin-polarization and strong out-of-plane magnetic
anisotropy; hence, they are ideal candidates for high-density-memory
applications. Tetragonal Heusler thin films with compensated magnetic state are
realized by substitution of Pt in Mn3-x Ptx Ga. Furthermore, the bilayer formed
from compensated/uncompensated Mn-Pt-Ga layers is utilized to accomplish exchange
bias up to room temperature.
PMID- 27500769
TI - [Postoperative applications of the fast track technology in patients with
herniated intervertebral discs of the lumbosacral spine].
AB - TOPICALITY: The fast track technology means a complex of targeted measures
involving rational preoperative preparation, minimally invasive surgery, regional
anesthesia and short-acting anesthetics, and early postoperative rehabilitation.
Elucidating the possibility of applying the fast track technology in
neurosurgery, in particular in spinal surgery, is extremely topical. This is
associated with the epidemiological data and the fact that minimally invasive
techniques used in neurosurgery are highly expensive. AIM: The study objective
was implementation of the fast track technology and subsequent analysis of its
use after surgery in patients with herniated intervertebral discs of the
lumbosacral spine. MATERIAL AND METHODS: The fast track technology following
spinal surgery was implemented at the Clinical Hospital of the Presidential
Administration of the Russian Federation and the Neurosurgical Department of the
Clinical Hospital No 1 of the Presidential Administration of the Russian
Federation using an algorithm of technology application. The study included 48
patients who underwent surgical treatment for herniated intervertebral discs of
the lumbosacral spine between January and July 2015. RESULTS: An analysis of pain
severity using the Visual Analog Scale demonstrated a slight decrease (10%) in a
group of patients who were subjected to the fast track technology, at discharge
and at 1 month after surgery; there was no difference in longer follow-up. An
analysis of the functional status using the Oswestry index and Roland-Morris
scale demonstrated that patients of the study group had faster and more efficient
recovery and an improvement of the functional activity by 20% (p<0.05) compared
to those in the control group. An analysis of patient-reported assessment of
treatment quality revealed that indicators, such as awareness and pain control,
in the study group were highest and amounted to 95% and higher. An analysis of
the hospital stay duration showed a decrease in the number of bed-days in an
integrated group by 39%, which saved 34 bed-days. CONCLUSION: The fast track
technology reduces the degree of surgical aggression, increases surgery safety,
and decreases the number of intraoperative complications and hospital stay
duration.
PMID- 27500770
TI - [Posterior decompression of the craniovertebral junction in children with Chiari
malformation: a surgery extent issue].
AB - AIM: The study objective was to develop a rational approach for defining the
extent of posterior decompression in children with Chiari 1 malformation.
MATERIAL AND METHODS: Posterior decompression was performed in 76 children with
Chiari 1 malformation, under 18 years of age, in the period between 2001 and
2015. Fifty two (68%) children had syringomyelia. Extradural decompression (EDD)
was performed in 14 (18%) cases, extra-arachnoid duraplasty (EAD) in 21 (28%)
cases, intra-arachnoid dissection and duraplasty in 21 (28%) cases, and foramen
of Magendie stenting and duraplasty in 20 (26%) cases. RESULTS: Complications
occurred in 15 (20%) patients, with one of them being fatal (case fatality rate,
1.3%). The complication rate was higher after (1) intra-arachnoid dissection
(p=0.0009) and stenting (p=0.02). Re-operation was required in 8 (11%) patients.
The overall rate of complications and re-operations was lowest after EAD (10%).
CONCLUSION: EAD is the method of choice for Chiari 1 malformation in children.
EDD can be adopted as a primary option, but it requires selection of relevant
patients. Intra-arachnoid dissection, with/without stenting, is not advisable as
a primary intervention, but may be inevitable in the re-operation case.
PMID- 27500771
TI - [Venous compression as a cause of trigeminal neuralgia].
AB - AIM: The study objective was to verify venous compression as a cause of
trigeminal neuralgia (TN) and to define the optimal surgical tactics for TN
patients. MATERIAL AND METHODS: Four hundred twenty one patients were operated on
for TN at the Neurosurgical Department of the City Hospital No2 from 1998 to
2015. Veins in the trigeminal nerve root entry zone, as a significant compression
factor, were identified in 40 patients (9.5%). Intraoperative data,
questionnaires, and self-assessment inventories were analyzed. Treatment outcomes
were assessed using the Barrow Neurological Institute (BNI) scale. RESULTS:
Patients with venous compression were divided into two groups. Eleven (27.5%)
patients in the first group had isolated venous compression. The feature of
microvascular decompression (MVD) in these patients was identification of all
veins, vein mobilization, and, if possible, vein coagulation and resection.
Resection of the vein along its course is a basic procedure to avoid recurrent
neuralgia. The second group included 29 (72.5%) patients with a combination of
venous and arterial compression. In these patients, a vein acted as an
"assisting" compression factor: the vein changed the course of a compressing
artery or nerve and exerted an additional compression effect on the nerve. The
surgical tactics involved exploration of the trigeminal nerve root entry zone,
arterial loop mobilization, and placement of a Teflon protector; venous vessels
were coagulated and resected. The MVD efficacy was as follows: in group 1, 10
patients had a BNI score I-III, and 1 patient had a BNI score IV; in group II, 25
patients had a BNI score I-III, and 4 patients had a BNI score IV. CONCLUSION:
Venous compression can play both independent and assisting roles in the TN
genesis. When exploring the trigeminal nerve, examination of the proximal
trigeminal nerve is of particular importance, with paying attention to veins that
may be a compression factor. In the case of isolated venous compression, the MVD
surgical technique has some peculiarities, in particular coagulation and
resection of veins compressing the trigeminal nerve root entry zone.
PMID- 27500772
TI - [Evaluation of short-term surgical outcomes in facial paralysis patients treated
by trigeminal neurotization].
AB - The management of patients with facial nerve palsy is a challenge of modern
neurosurgery. The study purpose was to evaluate the degree of facial nerve
function recovery, following trigeminal neurotization. Trigeminal neurotization
was performed in 23 patients within 1 to 10 months after the development of
facial paralysis. In most cases, the cause of facial paralysis was surgery for
space-occupying lesions of the cerebellopontine angle (95.6%). Outcomes of
trigeminal neurotization were evaluated in 17 (73.9%) patients who were followed
up for more than 6 months. In 16 (94.1%) patients, the facial nerve function was
recovered to a House-Brackmann grade III-IV. Given the surgery RESULTS: we can
say that trigeminal neurotization is one of the effective treatments for facial
paralysis. In most cases, this technique has provided good outcomes without
additional complications, which is important for this group of patients.
PMID- 27500773
TI - [Mini-orbitozygomatic craniotomy in surgery for supratentorial aneurysms and
tumors of the anterior and middle cranial fossae].
AB - Progress in microneurosurgical techniques, neuroanesthesiology, and
intraoperative imaging enables surgery using small incisions and craniotomy, in
accordance with the keyhole surgery concept. Supraorbital craniotomy is the most
widespread minimally invasive approach. There are a number of supraorbital
craniotomy modifications, regarding different soft tissue incisions and the
extent of craniotomy. We present the first results of using mini-orbitozygomatic
craniotomy for aneurysms of the anterior circle of Willis and space-occupying
lesions of the anterior and middle cranial fossae performed through an eyebrow
incision. MATERIAL AND METHODS: Forty five patients were operated on using mini
orbitozygomatic (MOZ) craniotomy in the period between March 2014 and December
2015. Fifteen supratentorial aneurysms were clipped, and 30 space-occupying
lesions were resected. Most patients had unruptured aneurysms (10 patients). Five
patients had a history of SAH. The aneurysm localization was as follows: 8
anterior communicating artery aneurysms, 4 aneurysms of the internal carotid
artery in the area of the posterior communicating artery orifice, and 3
ophthalmic aneurysms. The Hunt-Hess scale was used to evaluate the patients'
condition, and the Fisher scale was used to quantify SAH volume. Surgery was
performed 14 days after SAH, on average. Contrast-enhanced MRI of the brain was
the diagnostic method of choice in a group of patients with space-occupying
lesions within the anterior and middle cranial fossae. In some cases, patients
underwent CT with reconstruction for assessment of the skull base bone
structures. The mean age of patients was 58.3 years. RESULTS: All aneurysms were
completely excluded from the cerebral blood flow. No serious complications and
deaths in a group of aneurysm patients occurred. Complete tumor removal was
performed in 28 patients. Two patients having pituitary macroadenomas with supra-
and parasellar spread underwent subtotal resection due to adenoma invasion into
the cavernous sinus. Mortality in this group was 3.3% (1 patient). Postoperative
complications were evaluated after 2 weeks and 6 months. The postoperative
cosmetic result after 3 and 6 months after surgery was assessed by patients as
excellent. CONCLUSION: Mini-orbitozygomatic craniotomy is an alternative to
classic approaches and can be assistive in surgery for skull base aneurysms and
tumors. Selection of candidates for this keyhole surgery should be based on their
critical assessment.
PMID- 27500774
TI - [The paramedian supracerebellar transtentorial approach to the mediobasal
temporal region].
AB - The mediobasal temporal region (MTR) is located near the brain stem and
surrounded by the eloquent neurovascular structures. The supracerebellar
transtentorial approach (STA) is safe access to the posterior MTR structures,
however its use for resection of anterior MTR lesions still remains
controversial. The article describes the technique and outcome of surgery for
different MTR structures using STA. MATERIAL AND METHODS: The paramedian STA was
used in 18 patients (13 females and 5 males) for 7 years. Ten patients presented
with glial MTR tumors, 3 patients with cavernomas, 2 patients with arteriovenous
malformations (AVMs), 2 patients with intraventricular meningiomas, and 1 patient
with mesial temporal sclerosis. The patient age ranged from 19 to 57 years. In 10
cases, lesions were localized on the left. Epilepsy was the leading symptom in 14
cases. Patients underwent preoperative high-resolution MRI,
electroencephalography video monitoring before and after surgery, intraoperative
corticography (if necessary), and postoperative CT and MRI. RESULTS: Lesions were
located in the anterior third of MTR in 5 patients, in the anterior and middle
thirds in 2 patients, in the middle third in 5 patients, in the middle and
posterior thirds in 2 patients, in the posterior third in 1 patient, in the
anterior, middle, and posterior thirds in 1 patient, and in the ventricular
triangle area in 2 patients. In all patients with intraventricular tumors, AVMs,
and cavernous malformations and in 8 patients with glial MTR tumors, the lesions
were totally resected. Two patients with intracerebral tumors underwent subtotal
resection. A patient with intractable epilepsy and mesial temporal sclerosis
underwent resection of the anterior two-thirds of the hippocampus and
parahippocampal gyrus and, partially, amygdala using intraoperative
corticography. There was no surgical mortality; 2 patients developed a transient
neurological deficit, and 1 patient had a cerebellar hematoma that was
successfully removed during surgery. CONCLUSION: STA enables resection of lesions
localized in all parts of the MTR, without damage to the surrounding nerve and
vascular structures.
PMID- 27500775
TI - [Endoscopic transsphenoidal resection of pituitary adenomas invading the
cavernous sinus].
AB - INTRODUCTION: Pituitary adenomas are benign growths that invade the cavernous
sinus (CS) in 10-15% of cases. There are different types of microsurgical and
endoscopic approaches enabling resection of tumors from the CS cavity that is a
relatively small and hard to reach anatomical structure comprising eloquent
neurovascular structures. MATERIAL AND METHODS: A study group included 97
patients with pituitary adenomas (PAs) invading the CS. PAs were resected using
an endoscopic technique: adenomas were resected from the CS cavity through a
standard endoscopic endonasal transsphenoidal approach in 62 cases; a lateral
extended transsphenoidal endoscopic approach was used in 35 cases. A control
group included patients with PAs spreading into the laterosellar region who were
operated on using microsurgical extra-intradural (n=14) and transsphenoidal
(n=149) approaches. In the study group, the degree of PA invasion into the CS
cavity was determined using the Knosp scale. RESULTS: In the study group, total
tumor resection was achieved in 49 (50.5%) cases, subtotal resection in 39
(40.2%) cases, and partial resection in 9 (9.3%) patients. In the case of visual
disorders (n=70), vision improvement was achieved in 41.4% of cases. Vision
deterioration was detected in 11.4% of cases; no vision changes were in 47.1% of
cases. Patients (27.8%) who had not had visual impairments before surgery had no
negative changes in vision in the postoperative period. The
development/augmentation of oculomotor disorders in the study group occurred in
14 (14.4%) cases. In the study group, hormonal remission of the disease in
patients with hormone-active PAs was in 26.7% of cases (n=12). There were no
cases of nasal liquorrhea, meningitis, and death in the study group. CONCLUSION:
Endoscopic endonasal transsphenoidal resection of PAs invading the CS is a more
efficient and safer surgical technique compared to microsurgical techniques
(transsphenoidal and extra-intradural approach). The lateral extended
transsphenoidal endoscopic approach enables resection of PAs with massive
invasion into the CS (Grade III and Grade IV, Knosp scale) and has less
postoperative complications compared to the extra-intradural approach (p<0.05).
PMID- 27500776
TI - [Intramedullary melanocytoma: a clinical case report and literature review].
AB - The paper describes a rare clinical case of intramedullary melanocytoma, provides
a detailed description of a pathomorphological study, and addresses the issues of
differential diagnosis and surgical treatment.
PMID- 27500777
TI - [Cerebrospinal fluid shunt malfunction not associated with ventricular
enlargement. A case report and literature review].
AB - Substantiation of the shunt failure diagnosis and subsequent consideration of
indications for surgical elimination of the malfunction is a laborious and
challenging process. Identification of a malfunction in doubtful cases requires,
in addition to standard examinations, extra diagnostic procedures, which may
delay making a decision for several weeks to several months. The article
describes a case of mechanical CSF shunt malfunction (breakage and failure of a
peritoneal catheter in a 7-year-old girl) with intracranial hypertension
symptoms, but without typical enlargement of the brain ventricles. According to
the medical history, congenital hydrocephalus in the child was accompanied by an
inflammatory process of bacterial and viral etiology. The absence of brain
ventricle enlargement was shown not to exclude a probability of shunt
malfunction. In this case, a specific phenomenon, an intraparenchymatous
cerebrospinal fluid "lake" surrounding a ventricular catheter, was observed.
Shunting recovery did not lead to a significant reduction in the phenomenon size.
Causes underlying this phenomenon require further investigation.
PMID- 27500778
TI - [Treatment of patients with brain metastases].
PMID- 27500779
TI - DSM-5.1.
PMID- 27500780
TI - Using fluorescence lifetime microscopy to study the subcellular localization of
anthocyanins.
AB - Anthocyanins are flavonoid pigments that accumulate in most seed plants. They are
synthesized in the cytoplasm but accumulate inside the vacuoles. Anthocyanins are
pigmented at the lower vacuolar pH, but in the cytoplasm they can be visualized
based on their fluorescence properties. Thus, anthocyanins provide an ideal
system for the development of new methods to investigate cytoplasmic pools and
association with other molecular components. We have analyzed the fluorescence
decay of anthocyanins by fluorescence lifetime imaging microscopy (FLIM), in both
in vitro and in vivo conditions, using wild-type and mutant Arabidopsis thaliana
seedlings. Within plant cells, the amplitude-weighted mean fluorescence lifetime
(taum ) correlated with distinct subcellular localizations of anthocyanins. The
vacuolar pool of anthocyanins exhibited shorter taum than the cytoplasmic pool.
Consistently, lowering the pH of anthocyanins in solution shortened their
fluorescence decay. We propose that FLIM is a useful tool for understanding the
trafficking of anthocyanins and, potentially, for estimating vacuolar pH inside
intact plant cells.
PMID- 27500781
TI - Depressed-type submucosal invasive colorectal cancer in a patient with Lynch
syndrome diagnosed using short-interval colonoscopy.
AB - Although regular colonoscopy surveillance is recommended for patients with Lynch
syndrome (LS) who underwent partial colectomy, the appropriate interval has not
been determined. We report a case of colorectal cancer (CRC) detected by short
interval surveillance colonoscopy (SC) in a patient with LS having a past history
of partial colectomy. A 65-year-old man underwent sigmoidectomy for advanced CRC.
His family history revealed that his two younger brothers had CRC in their
twenties and thirties, respectively, and the patient met with the criteria in the
Revised Bethesda Guidelines. After confirming the loss of MSH2 protein expression
in the primary tumor, subsequent genetic testing showed germline mutation with a
large deletion of exon 7-14 in the MSH2 gene, indicating a diagnosis of LS. After
the diagnosis of LS, the patient underwent annual SC. Three years after the
initial surgery, superficial submucosal invasive cancer was detected.
Subsequently, SC after a 6-month interval revealed a deep submucosal invasive
cancer (7 mm in diameter). Although additional surgery was recommended,
considering his comorbidities, regular SC rather than colectomy was selected.
Even shorter-interval SC carried out within a year is not sufficient to detect
endoscopically resectable tumors in some high-risk LS cases.
PMID- 27500783
TI - Myeloproliferative neoplasms: trends in incidence, prevalence and survival in
Norway.
AB - BACKGROUND: Polycythemia vera (PV), essential thrombocythemia (ET) and
myelofibrosis (MF) are clonal disorders collectively named as myeloproliferative
neoplasms (MPN). Published data on epidemiology of MPN after the discovery of the
JAK2 mutation and the 2008 WHO classifications are scarce. We aimed to study the
incidence rates, prevalence and survival of MPN in Norway during the period 1993
2012. METHOD: We identified 2453 persons diagnosed with MPN from the Cancer
Registry of Norway between 1993 and 2012. We report age-adjusted incidence rates,
prevalence, relative survival and standardised mortality rates. RESULTS: The
overall age-adjusted yearly incidence rate of PV increased from 0.4/105 to
0.7/105, ET increased from 0.3/105 to 1.0/105 and MF from 0.2/105 to 0.5/105.
Prevalence of PV, ET and MF was 9.2, 8.6 and 3.0 per 105 inhabitants,
respectively. The five-year relative survival (RS) of ET and PV was slightly
reduced with no improvement. The five-year RS of MF was 58.1% (2008-2012).
Standardised mortality rate (SMR) was 1.9 (95% CI 1.2 - 2.7). CONCLUSIONS: The
incidence rates of ET, PV and MF doubled and tripled during the years 2007-2012
as compared to 1995-2006. This increment in incidence rates may be related to
identification of the JAK2 mutation and the derived 2008 WHO guidelines for MPN.
The RS was only slightly reduced in PV and ET, but was substantially reduced in
MF.
PMID- 27500782
TI - Autologous tendon-derived cell-seeded nanofibrous scaffolds improve rotator cuff
repair in an age-dependent fashion.
AB - Rotator cuff tendon tears are one of the most common shoulder pathologies,
especially in the aging population. Due to a poor healing response and
degenerative changes associated with aging, rotator cuff repair failure remains
common. Although cell-based therapies to augment rotator cuff repair appear
promising, it is unknown whether the success of such a therapy is age-dependent.
We hypothesized that autologous cell therapy would improve tendon-to-bone healing
across age groups, with autologous juvenile cells realizing the greatest benefit.
In this study, juvenile, adult, and aged rats underwent bilateral supraspinatus
tendon repair with augmentation of one shoulder with autologous tendon-derived
cell-seeded polycaprolactone scaffolds. At 8 weeks, shoulders treated with cells
in both juvenile and aged animals exhibited increased cellularity, increased
collagen organization, and improved mechanical properties. No changes between
treated and control limbs were seen in adult rats. These findings suggest that
cell delivery during supraspinatus repair initiates earlier matrix remodeling in
juvenile and aged animals. This may be due to the relative "equilibrium" of adult
tendon tissue with regards to catabolic and anabolic processes, contrasted with
actively growing juvenile tendons and degenerative aged tendons. This study
demonstrates the potential for autologous cell-seeded scaffolds to improve
repairs in both the juvenile and aged population. (c) 2016 Orthopaedic Research
Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1250-1257, 2017.
PMID- 27500784
TI - Effects of QMix and ethylenediaminetetraacetic acid on decalcification and
erosion of root canal dentin.
AB - The aim of this study was to evaluate the effect of initial NaOCl on the
decalcification and erosion ability of EDTA and QMix. Sixty-maxillary-incisors
were bisected longitudinally and the tooth-halves were used. The experiment was
conducted in two-sets. In set-I, 80-tooth halves were treated in the presence or
absence of initial NaOCl and EDTA. In set-II, 40-tooth halves were immersed in
NaOCl and QMix. After each treatment, calcium-ion release was determined with
flame photometry. The erosion was imaged using SEM. Initial NaOCl led to
concentration- and time-dependent increase in calcium removal effect of 17% EDTA
(p < .05). The rate of calcium removal and root canal wall erosion was
considerably more severe with the use of 5% NaOCl for 3 min (p < .05). QMix as a
final solution showed less decalcification and erosion than 17% EDTA when used 5%
NaOCl as an initial irrigant (p < .05). Optimizing the concentration and
application time of NaOCl can decrease the decalcification effect of chelating
agents.
PMID- 27500785
TI - Pathways of protein and lipid receptor-mediated transcytosis in drug delivery.
AB - INTRODUCTION: A critical factor for the efficacy of drugs is their availability
at the site of interest. However, crossing endothelial and epithelial cell layers
like the blood-brain barrier and the blood-intestinal barrier represents a major
bottleneck for drug targeting. Coupling drugs to carriers that recognize
endogenous receptors, which are then transported through cell layers by
transcytosis, is a promising approach to overcome this bottleneck. Areas covered:
This review focuses on the intracellular pathways of receptor-mediated
transcytosis and their applicability for transcellular drug delivery. It gives an
overview about transcytotic trafficking routes in epithelia and highlights the
well-studied examples of immungobulin transcytosis and transferrin transcytosis.
The current knowledge about the less understood transcytosis pathways in
endothelia is also summarized and low-density lipoprotein transcytosis is
described. In addition, transcytosis pathways that are based on
glycosphingolipids and lectins as their receptors are presented. Expert opinion:
Multiple transcellular drug delivery approaches based on proteinaceous receptors
have been developed in recent years, whereas lectins that bind to
glycosphingolipids emerge as promising alternative. Closer investigation of
endogenous transcytosis mechanisms, especially in endothelia, will be a fruitful
endeavor to devise more optimized carriers for transcytotic drug delivery.
PMID- 27500786
TI - Morpho-histological and ultra architectural changes during early development of
endangered golden mahseer Tor putitora.
AB - Ultrastructural and histological changes in the embryonic and larval surface
during ontogenesis of the endangered golden mahseer Tor putitora is studied here
for the first time. Embryonic development was completed 91-92 h after
fertilization at an ambient temperature of 23 degrees +/- 1 degrees C (mean +/-
s.d.). The gastrula stage was characterized by presence of the Kupffer's vesicle,
notochord, ectoderm and endoderm cells. Primordial germ cells were clearly
identifiable from c. 55 h post-fertilization at the organogenesis stage. Mean
total length of newly hatched larvae was 7.0 +/- 0.5 mm. Scanning electron
microscopy of newly hatched larvae demonstrated vitelline arteries, microridged
epithelial cells and mucous gland openings over much of the body surface. Eye,
oral cavity, pharyngeal arches, heart, intestinal loop, prosencephalon, cephalic
vesicle and nasal epithelium were clearly distinguished in 3 day old hatched
individuals. In 6 day old individuals, caudal-fin rays and internal organs were
evident. The dorsal fin became prominent at this stage and larvae began swimming
at the surface. The reserved yolk material was totally absorbed 8-11 days after
hatching and larvae began feeding exogenously. Tor putitora exhibited a longer
early developmental period than other cyprinids reared at similar temperatures.
PMID- 27500787
TI - Association of Interleukin 10 Gene Polymorphisms with Autoimmune Thyroid Disease:
Meta-Analysis.
AB - The aim of this study was to perform a meta-analysis of eligible studies and to
derive a precise estimate of the association between interleukin 10 (IL10)
polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta
analyses were conducted on the associations between AITD and the -1082 G/A
(rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms in IL10,
and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients
and 3060 controls in 10 eligible studies were included in the meta-analysis. This
meta-analysis showed significant associations between IL10 at the -1082 G allele
and overall AITD (OR: 1.44, 95% CI 1.13-1.82, P = 0.003), but no association
between the IL10 -592 C allele and the -819 C allele and AITD. Subgroup studies
demonstrated significant associations between the -1082 G allele and
susceptibility to Graves' disease. Ethnicity-specific meta-analysis revealed
significant associations between the -1082 G allele and AITD susceptibility in
Asian populations; however, in Middle Eastern populations, no association was
evident. Meta-analysis of the IL10 haplotype revealed an association between the
ATA haplotype and AITD (OR: 1.17, 95% CI 1.00-1.36, P = 0.04). Meta-analysis
demonstrates that the IL10 polymorphisms are associated with susceptibility to
AITD.
PMID- 27500788
TI - Rural-Urban Differences in the Effect of Follow-Up Care on Postdischarge
Outcomes.
AB - OBJECTIVE: To assess rural-urban differences in quality of postdischarge care
among Medicare beneficiaries, controlling for selection bias of postdischarge
services. DATA SOURCES: The Medicare Current Beneficiary Survey (MCBS), Cost and
Use Files from 2000 to 2010, the Area Resource File, Provider of Services File,
and the Dartmouth Atlas of Health Care. STUDY DESIGN: Retrospective analysis of
30- and 60-day hospital readmission, emergency department (ED) use, and mortality
using two-stage residual inclusion; receipt of 14-day follow-up care was the main
independent variable. DATA EXTRACTION METHOD: We defined index admission from the
MCBS as any admission without a previous admission within 60 days. PRINCIPAL
FINDINGS: Noninstrumental variables estimation was the preferred estimation
strategy. Fourteen-day follow-up care reduced the risk of readmission, ED use,
and mortality. There were no rural- urban differences in the effect of 14-day
follow-up care on readmission and mortality. Rural beneficiaries experienced a
greater effect of 14-day follow-up care on reducing 30-day ED use compared to
urban beneficiaries. CONCLUSIONS: Follow-up care reduces 30- and 60-day
readmission, ED use, and mortality. Rural and urban Medicare beneficiaries
experience similar beneficial effects of follow-up care on the outcomes. Policies
that improve follow-up care in rural settings may be beneficial.
PMID- 27500789
TI - CO2 Reduction Catalyzed by Nitrogenase: Pathways to Formate, Carbon Monoxide, and
Methane.
AB - The reduction of N2 to NH3 by Mo-dependent nitrogenase at its active-site metal
cluster FeMo-cofactor utilizes reductive elimination of Fe-bound hydrides with
obligatory loss of H2 to activate the enzyme for binding/reduction of N2. Earlier
work showed that wild-type nitrogenase and a nitrogenase with amino acid
substitutions in the MoFe protein near FeMo-cofactor can catalytically reduce CO2
by two or eight electrons/protons to carbon monoxide (CO) and methane (CH4) at
low rates. Here, it is demonstrated that nitrogenase preferentially reduces CO2
by two electrons/protons to formate (HCOO(-)) at rates >10 times higher than
rates of CO2 reduction to CO and CH4. Quantum mechanical calculations on the
doubly reduced FeMo-cofactor with a Fe-bound hydride and S-bound proton (E2(2H)
state) favor a direct reaction of CO2 with the hydride ("direct hydride transfer"
reaction pathway), with facile hydride transfer to CO2 yielding formate. In
contrast, a significant barrier is observed for reaction of Fe-bound CO2 with the
hydride ("associative" reaction pathway), which leads to CO and CH4. Remarkably,
in the direct hydride transfer pathway, the Fe-H behaves as a hydridic hydrogen,
whereas in the associative pathway it acts as a protic hydrogen. MoFe proteins
with amino acid substitutions near FeMo-cofactor (alpha-70(Val->Ala), alpha
195(His->Gln)) are found to significantly alter the distribution of products
between formate and CO/CH4.
PMID- 27500790
TI - A Protocol for the Production of Gliadin-cyanoacrylate Nanoparticles for
Hydrophilic Coating.
AB - This article presents a protocol for the production of protein-based
nanoparticles that changes the hydrophobic surface to hydrophilic by a simple
spray coating. These nanoparticles are produced by the polymerization reaction of
alkyl cyanoacrylate on the surface of cereal protein (gliadin) molecules. Alkyl
cyanoacrylate is a monomer that instantly polymerizes at RT when it is applied to
the surface of materials. Its polymerization reaction is initiated by the trace
amounts of weakly basic or nucleophilic species on the surface, including
moisture. Once polymerized, the polymerized alkyl cyanoacrylates show a strong
affinity with the object materials because nitrile groups are in the backbone of
poly (alkyl cyanoacrylate). Proteins also work as initiator for this
polymerization because they contain amine groups that can initiate the
polymerization of cyanoacrylate. If aggregated protein is used as an initiator,
protein aggregate is surrounded by the hydrophobic poly(alkyl cyanoacrylate)
chains after the polymerization reaction of alkyl cyanoacrylate. By controlling
the experimental condition, particles in the nanometer range are produced. The
produced nanoparticles readily adsorb to the surface of most materials including
glass, metals, plastics, wood, leather, and fabrics. When the surface of a
material is sprayed with the produced nanoparticle suspension and rinsed with
water, the micellar structure of nanoparticle changes its conformation, and the
hydrophilic proteins are exposed to the air. As a result, the nanoparticle-coated
surface changes to hydrophilic.
PMID- 27500792
TI - Development and preliminary evaluation of culturally specific web-based
intervention for parents of adolescents.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Problematic parent-child relationships have been
identified as one of the main predictors of adolescents' mental health problems,
but there are few existing interventions that address this issue. The format and
delivery method of existing interventions for parents are relatively inaccessible
for parents with full-time jobs and families living in rural areas. WHAT DOES
THIS PAPER ADD TO EXISTING KNOWLEDGE?: The newly developed 'Stepping Stone'
culturally specific web-based intervention, which is intended to help Korean
parents of adolescents to acquire both knowledge and communication and conflict
management skills, was found to be feasible and well-accepted by parents. This
study enabled us to identify areas for improvement in the content and format of
the intervention and strategies. This will potentially increase effect sizes for
the outcome variables of parents' perception and behaviours. WHAT ARE THE
IMPLICATIONS FOR PRACTICE?: This web-based intervention could be delivered across
diverse settings, such as schools and community mental health centers, to
increase parents' knowledge of adolescent's mental health and allow for early
detection of mental health problems. Mental health nurses working in schools may
spend a significant amount of time addressing students' mental health issues;
thus, this web-based intervention could be a useful resource to share with
parents and children. In this way, the mental health nurses could facilitate
parental engagement in the intervention and then help them to continue to apply
and practice the knowledge and skills obtained through the program. ABSTRACT:
Introduction There is a need for accessible, culturally specific web-based
interventions to address parent-child relationships and adolescents' mental
health. Aims This study developed and conducted a preliminary evaluation of a 4
week web-based intervention for parents of adolescents aged 11 to 16 years in
Korea. Methods We used a two-group, repeated measures, quasi-experimental study
design to assess the feasibility of developing and implementing a web-based
intervention for parents. Descriptive statistics, chi-square and t tests, and
mixed effect modeling were used for data analysis. Results The intervention and 1
month follow-up survey were completed by 47 parents in the intervention group and
46 parents in the attention control (AC) group. The intervention was found to be
feasible and well-accepted by parents. Discussion This culturally specific web
based intervention is a useful tool for knowledge dissemination among large
numbers of parents. Areas for improvement in the content and format of the
intervention and strategies to elicit significant parent-child interactions are
provided. Implications for practice and conclusion The intervention could be
disseminated in collaboration with mental health nurses working in schools to
facilitate parents' participation.
PMID- 27500791
TI - Highlights From the American Association of Pharmaceutical Scientists/
International Transporter Consortium Joint Workshop on Drug Transporters in
Absorption, Distribution, Metabolism, and Excretion: From the Bench to the
Bedside - Clinical Pharmacology Considerations.
AB - The American Association of Pharmaceutical Scientists/International Transporter
Consortium Joint Workshop on Drug Transporters in absorption, distribution,
metabolism, and excretion was held with the objective of discussing innovative
advances in transporter pharmacology. Specific topics included (i) transporters
at the blood-brain barrier (BBB); (ii) emerging transport proteins; (iii) recent
advances in achieving hepatoselectivity and optimizing clearance for organic
anion-transporting polypeptide (OATP) substrates; (iv) utility of animal models
for transporter studies; and (v) clinical correlation of transporter
polymorphisms. Here, we present state-of-the-art highlights from this workshop in
these key areas of focus.
PMID- 27500793
TI - Pathogen and antimicrobial resistance profiles of culture-proven neonatal sepsis
in Southwest China, 1990-2014.
AB - AIM: Neonatal sepsis (NS) sustains high mortality and morbidity in China, but
data on the epidemiology and antimicrobial resistance patterns of NS pathogens
are limited. METHODS: The clinical features, aetiology and antimicrobial
resistance of culture-proven NS were analysed over a period of 25 years in the
metropolitan city of Chongqing in Southwest China. RESULTS: The occurrence rates
of neonatal early-onset sepsis (EOS) were found to gradually decrease while late
onset sepsis (LOS) was kept stable from 1990 to 2014. Although coagulase-negative
staphylococcus (CoNS) sepsis accounted for most infections, the occurrence rates
of CoNS sepsis gradually decreased, especially in EOS. Escherichia coli and
Klebsiella were common Gram-negative bacteria. The occurrence rates of E. coli
and Klebsiella remained stable in EOS; however, in LOS, those had increased
mildly, especially from 2009 to 2014. Although a high-degree resistance to common
first- and second-line antimicrobials was observed for the main causative
pathogens of NS, the gentamicin-resistance rate declined gradually from the year
2003. Similarly, the ceftazidime-resistance rate of E. coli dropped gradually
from the year 2007. CONCLUSIONS: The alarmingly high degree of antibiotic
resistance calls for urgent evaluation and development of antibiotic policy and
protocols for the treatment of NS. Clinicians should strictly control the
antibiotics use, decrease invasive manipulations and shorten hospitalisation to
prevent LOS.
PMID- 27500794
TI - Current perspective on actinic keratosis: a review.
AB - Actinic keratoses (AKs) are common, with prevalence in the U.S.A. estimated at
almost 40 million in 2004 and annual costs of > $1 billion (U.S.D.). However,
there is no universally accepted definition of AK and thus it is difficult to
identify reliably. AKs are lesions of epidermal keratinocytic dysplasia that
result from chronic sun exposure and have the ability to progress to invasive
squamous cell carcinoma (SCC), but clinicians disagree about whether AKs are
premalignant lesions, superficial SCCin situ or epiphenomena of chronically sun
damaged skin. Yearly AK to SCC progression rates of 0.6% were reported in an
elderly population with multiple prior keratinocyte carcinomas (KCs); and rates
of spontaneous AK regression have been reported to be > 50%, but regressed
lesions often reappear. As AKs have both cosmetic consequences and potential for
malignant transformation, there are multiple reasons for treatment. There is no
current agreement on the most efficacious treatment, but 5-fluorouracil has been
shown to both prevent and treat AKs, and imiquimod and photodynamic therapy may
have the best cosmetic outcomes. AKs may be treated to improve appearance and
relieve symptoms, but the keratinocytic dysplasia that gives rise to malignancy,
and sometimes appears as an AK, may be what actually threatens patient health.
Thus, treatments should aim to decrease the risk of KC or facilitate KC diagnosis
by reducing the potential for misidentification created when a KC appears in a
field of AKs. Improved agreement among clinicians on AK definition may improve
management.
PMID- 27500795
TI - Environmental factors, life events, and trauma in the course of bipolar disorder.
AB - The etiology and clinical course of bipolar disorder are considered to be
determined by genetic and environmental factors. Although the kindling hypothesis
emphasizes the impact of environmental factors on initial onset, their connection
to the outcome and clinical course have been poorly established. Hence, there
have been numerous research efforts to investigate the impact of environmental
factors on the clinical course of illness. Our aim is to outline recent research
on the impact of environmental determinants on the clinical course of bipolar
disorder. We carried out a computer-aided search to find publications on an
association between environmental factors, life events, and the clinical course
of bipolar disorder. Publications in the reference lists of suitable papers have
also been taken into consideration. We performed a narrative overview on all
eligible publications. The available body of data supports an association between
environmental factors and the clinical course of bipolar disorder. These factors
comprise prenatal, early-life, and entire lifespan aspects. Given varying sample
sizes and several methodological limitations, the reported quality and extent of
the association between environmental factors and the clinical course of bipolar
disorder should be interpreted with utmost caution. Systematic longitudinal long
term follow-up trials are needed to obtain a clearer and more robust picture.
PMID- 27500799
TI - A Route to the C,D,E Ring System of the Aspidosperma Alkaloids.
AB - A short synthetic sequence leading to the formation of the C,D,E-ring subunit of
the Aspidosperma alkaloids is reported. This route is based on a ring
fragmentation/intramolecular azomethine ylide 1,3-dipolar cycloaddition reaction
sequence that gives the desired tricyclic product as a single diastereomer. A
gamma-amino-beta-hydroxy-alpha-diazo carbonyl compound is shown to fragment in
the presence of a Lewis acid to give an iminium product that can be directly
reduced to the corresponding amine.
PMID- 27500800
TI - Hydroponics: A Versatile System to Study Nutrient Allocation and Plant Responses
to Nutrient Availability and Exposure to Toxic Elements.
AB - Hydroponic systems have been utilized as one of the standard methods for plant
biology research and are also used in commercial production for several crops,
including lettuce and tomato. Within the plant research community, numerous
hydroponic systems have been designed to study plant responses to biotic and
abiotic stresses. Here we present a hydroponic protocol that can be easily
implemented in laboratories interested in pursuing studies on plant mineral
nutrition. This protocol describes the hydroponic system set up in detail and the
preparation of plant material for successful experiments. Most of the materials
described in this protocol can be found outside scientific supply companies,
making the set up for hydroponic experiments less expensive and convenient. The
use of a hydroponic growth system is most advantageous in situations where the
nutrient media need to be well controlled and when intact roots need to be
harvested for downstream applications. We also demonstrate how nutrient
concentrations can be modified to induce plant responses to both essential
nutrients and toxic non-essential elements.
PMID- 27500801
TI - Analgesic efficacy of equimolar 50% nitrous oxide/oxygen gas premix (Kalinox(r))
as compared with a 5% eutectic mixture of lidocaine/prilocaine (EMLA(r)) in
chronic leg ulcer debridement.
AB - Chronic foot and leg ulcers are a common health problem worldwide. A mainstay of
chronic ulcer therapy is sharp mechanical wound debridement requiring potent
analgesia. In this prospective, controlled, single-centre, crossover design
study, patients were assigned to either the administration of topical analgesia
with 5% lidocaine/prilocaine cream or the inhalation of an analgesic 50% N2 O/O2
gas premix. Primary outcome parameter was level of pain at maximum wound depth
during debridement as measured by a visual analogue scale. Secondary outcomes
included level of pain after debridement, overall duration of treatment session,
duration and completeness of debridement, and the patient's subjective perception
of analgesic quality during debridement. Pain level increased from 0.60/0.94
(first/second debridement; baseline) to 1.76/2.50 (debridement) with 5%
lidocaine/prilocaine and from 1.00/1.35 (baseline) to 3.95/3.29 (debridement)
with 50% N2 O/O2 gas premix. Patient satisfaction was 90.48%/94.44% (first/second
debridement) with topical 5% lidocaine/prilocaine analgesia and 90.48%/76.47%
with the inhalation of 50% N2 O/O2 gas premix. Debridement was completed in a
significantly higher percentage of 85.71%/88.89% (first/second debridement) with
5% lidocaine/prilocaine than with 50% N2 O/O2 gas premix (42.86%/58.82%) (odds
ratio 6.7; P = 0.001). This study provides sound evidence that analgesia with
topically administered 5% lidocaine/prilocaine cream is superior to the use of
inhaled 50% N2 O/O2 gas premix in chronic leg ulcer debridement.
PMID- 27500802
TI - A Chemically Programmed Proximal Ligand Enhances the Catalytic Properties of a
Heme Enzyme.
AB - Enzymes rely on complex interactions between precisely positioned active site
residues as a mechanism to compensate for the limited functionality contained
within the genetic code. Heme enzymes provide a striking example of this
complexity, whereby the electronic properties of reactive ferryl intermediates
are finely tuned through hydrogen bonding interactions between proximal ligands
and neighboring amino acids. Here, we show that introduction of a chemically
programmed proximal Ndelta-methyl histidine (NMH) ligand into an engineered
ascorbate peroxidase (APX2) overcomes the reliance on the conserved Asp-His
hydrogen bonding interaction, leading to a catalytically modified enzyme (APX2
NMH), which is able to achieve a significantly higher number of turnovers
compared with APX2 without compromising catalytic efficiency. Structural,
spectroscopic and kinetic characterization of APX2 NMH and several active site
variants provides valuable insights into the role of the Asp-His-Fe triad of heme
peroxidases. More significantly, simplification of catalytic mechanisms through
the incorporation of chemically optimized ligands may facilitate efforts to
create and evolve new active site heme environments within proteins.
PMID- 27500803
TI - Fabrication and electrokinetic motion of electrically anisotropic Janus droplets
in microchannels.
AB - This paper presents experimental investigations of the fabrication and the motion
of electrically anisotropic Janus droplets in a microchannel under externally
applied direct current (DC) electrical field. The fabrication method of the Janus
droplets is presented first. To begin, oil droplets are coated uniformly with
positively charged nanoparticles in the aluminum oxide nanoparticle suspension.
The electrically anisotropic Janus droplets are formed when the nanoparticles are
accumulated to one side of the droplets in response to externally applied DC
electric field. The surface coverage of the Janus droplets by nanoparticles can
be adjusted by controlling the concentration of the nanoparticle suspension. The
flow fields around the Janus droplets moving in a microchannel were observed with
tracing particles. Finally, the electrokinetic velocity of the Janus droplets in
a microchannel was measured. The effects of the strength of the electrical field,
the surface coverage of the Janus droplets by nanoparticles, the size of the
droplets as well as the electrolyte concentration on the electrokinetic velocity
of the Janus droplets were studied.
PMID- 27500804
TI - Proton-Coupled Electron Transfer Reactions with Photometric Bases Reveal Free
Energy Relationships for Proton Transfer.
AB - The proton-coupled electron transfer (PCET) oxidation of p-aminophenol in
acetonitrile was initiated via stopped-flow rapid-mixing and spectroscopically
monitored. For oxidation by ferrocenium in the presence of 7
(dimethylamino)quinoline proton acceptors, both the electron transfer and proton
transfer components could be optically monitored in the visible region; the decay
of the ferrocenium absorbance is readily monitored (lambdamax = 620 nm), and the
absorbance of the 2,4-substituted 7-(dimethylamino)quinoline derivatives
(lambdamax = 370-392 nm) red-shifts substantially (ca. 70 nm) upon protonation.
Spectral analysis revealed the reaction proceeds via a stepwise electron transfer
proton transfer process, and modeling of the kinetics traces monitoring the
ferrocenium and quinolinium signals provided rate constants for elementary proton
and electron transfer steps. As the pKa values of the conjugate acids of the 2,4
R-7-(dimethylamino)quinoline derivatives employed were readily tuned by varying
the substituents at the 2- and 4-positions of the quinoline backbone, the driving
force for proton transfer was systematically varied. Proton transfer rate
constants (kPT,2 = (1.5-7.5) * 10(8) M(-1) s(-1), kPT,4 = (0.55-3.0) * 10(7) M(
1) s(-1)) were found to correlate with the pKa of the conjugate acid of the
proton acceptor, in agreement with anticipated free energy relationships for
proton transfer processes in PCET reactions.
PMID- 27500806
TI - Polariton condensates: Electrical spin switching.
PMID- 27500805
TI - Design of efficient molecular organic light-emitting diodes by a high-throughput
virtual screening and experimental approach.
AB - Virtual screening is becoming a ground-breaking tool for molecular discovery due
to the exponential growth of available computer time and constant improvement of
simulation and machine learning techniques. We report an integrated organic
functional material design process that incorporates theoretical insight, quantum
chemistry, cheminformatics, machine learning, industrial expertise, organic
synthesis, molecular characterization, device fabrication and optoelectronic
testing. After exploring a search space of 1.6 million molecules and screening
over 400,000 of them using time-dependent density functional theory, we
identified thousands of promising novel organic light-emitting diode molecules
across the visible spectrum. Our team collaboratively selected the best
candidates from this set. The experimentally determined external quantum
efficiencies for these synthesized candidates were as large as 22%.
PMID- 27500807
TI - A sub-femtojoule electrical spin-switch based on optically trapped polariton
condensates.
AB - Practical challenges to extrapolating Moore's law favour alternatives to
electrons as information carriers. Two promising candidates are spin-based and
all-optical architectures, the former offering lower energy consumption, the
latter superior signal transfer down to the level of chip-interconnects.
Polaritons-spinor quasi-particles composed of semiconductor excitons and
microcavity photons-directly couple exciton spins and photon polarizations,
combining the advantages of both approaches. However, their implementation for
spintronics has been hindered because polariton spins can be manipulated only
optically or by strong magnetic fields. Here we use an external electric field to
directly control the spin of a polariton condensate, bias-tuning the emission
polarization. The nonlinear spin dynamics offers an alternative route to
switching, allowing us to realize an electrical spin-switch exhibiting ultralow
switching energies below 0.5 fJ. Our results lay the foundation for development
of devices based on the electro-optical control of coherent spin ensembles on a
chip.
PMID- 27500810
TI - Top-down and bottom-up guidance in comprehension of schematic football diagrams.
AB - Comprehension of a narrated diagram entail complex cognitive processing as
learner is challenged to extract the orally evoked information. The present
experiment examined the effects of 2 different forms of attention guidance -
bottom-up and top-down - on comprehension performance, cognitive load investment,
and motivation to learn, using a 2 * 2 mixed design with factors "Expertise"
(Expert vs. Novice) and "Condition" (no-signal, circle, segment). The results
revealed an expertise reversal effect indicating that the incorporation of visual
signals in diagram is effective for novice learners but partially reverses and
becomes ineffective for more experienced learners (even though they invested less
mental effort and reported higher level of motivation in the segmented
condition). The findings suggested that the effectiveness of instructional
guidance depends heavily on levels of prior knowledge.
PMID- 27500809
TI - The nanocomposite nature of bone drives its strength and damage resistance.
AB - In human bone, an amorphous mineral serves as a precursor to the formation of a
highly substituted nanocrystalline apatite. However, the precise role of this
amorphous mineral remains unknown. Here, we show by using transmission electron
microscopy that 100-300 nm amorphous calcium phosphate regions are present in the
disordered phase of trabecular bone. Nanomechanical experiments on cylindrical
samples, with diameters between 250 nm and 3,000 nm, of the bone's ordered and
disordered phases revealed a transition from plastic deformation to brittle
failure and at least a factor-of-2 higher strength in the smaller samples. We
postulate that this transition in failure mechanism is caused by the suppression
of extrafibrillar shearing in the smaller samples, and that the emergent smaller
is-stronger size effect is related to the sample-size scaling of the distribution
of flaws. Our findings should help in the understanding of the multi-scale nature
of bone and provide insights into the biomineralization process.
PMID- 27500808
TI - Detection and imaging of quorum sensing in Pseudomonas aeruginosa biofilm
communities by surface-enhanced resonance Raman scattering.
AB - Most bacteria in nature exist as biofilms, which support intercellular signalling
processes such as quorum sensing (QS), a cell-to-cell communication mechanism
that allows bacteria to monitor and respond to cell density and changes in the
environment. As QS and biofilms are involved in the ability of bacteria to cause
disease, there is a need for the development of methods for the non-invasive
analysis of QS in natural bacterial populations. Here, by using surface-enhanced
resonance Raman scattering spectroscopy, we report rationally designed
nanostructured plasmonic substrates for the in situ, label-free detection of a QS
signalling metabolite in growing Pseudomonas aeruginosa biofilms and
microcolonies. The in situ, non-invasive plasmonic imaging of QS in biofilms
provides a powerful analytical approach for studying intercellular communication
on the basis of secreted molecules as signals.
PMID- 27500812
TI - Role of Dual-Hormone Closed-Loop Delivery System in the Future.
PMID- 27500813
TI - I. WORKING MEMORY CAPACITY IN CONTEXT: MODELING DYNAMIC PROCESSES OF BEHAVIOR,
MEMORY, AND DEVELOPMENT.
AB - Working memory is a vital cognitive skill that underlies a broad range of
behaviors. Higher cognitive functions are reliably predicted by working memory
measures from two domains: children's performance on complex span tasks, and
infants' performance in looking paradigms. Despite the similar predictive power
across these research areas, theories of working memory development have not
connected these different task types and developmental periods. The current
project takes a first step toward bridging this gap by presenting a process
oriented theory, focusing on two tasks designed to assess visual working memory
capacity in infants (the change-preference task) versus children and adults (the
change detection task). Previous studies have shown inconsistent results, with
capacity estimates increasing from one to four items during infancy, but only two
to three items during early childhood. A probable source of this discrepancy is
the different task structures used with each age group, but prior theories were
not sufficiently specific to explain how performance relates across tasks. The
current theory focuses on cognitive dynamics, that is, how memory representations
are formed, maintained, and used within specific task contexts over development.
This theory was formalized in a computational model to generate three
predictions: 1) capacity estimates in the change-preference task should continue
to increase beyond infancy; 2) capacity estimates should be higher in the change
preference versus change detection task when tested within individuals; and 3)
performance should correlate across tasks because both rely on the same
underlying memory system. I also tested a fourth prediction, that development
across tasks could be explained through increasing real-time stability, realized
computationally as strengthening connectivity within the model. Results confirmed
these predictions, supporting the cognitive dynamics account of performance and
developmental changes in real-time stability. The monograph concludes with
implications for understanding memory, behavior, and development in a broader
range of cognitive development.
PMID- 27500811
TI - Immune deficiency in chronic rhinosinusitis: screening and treatment.
AB - INTRODUCTION: Chronic rhinosinusitis (CRS) is a prevalent disease with a high
annual cost of treatment. Immune deficiencies are more common in individuals with
CRS and should be especially considered in those patients who are refractory to
medical and surgical therapy. Areas covered: We performed a literature search in
PubMed of the terms "immunodeficiency" and "sinusitis" or "rhinosinusitis" from
2006 through March 2016. All abstracts were reviewed to determine if they
pertained to human disease; relevant articles were evaluated in their entirety
and included in this review. Expert commentary: CRS is a common disease; in those
patients with frequent exacerbations or who are refractory to treatment, an
immunodeficiency evaluation should be considered. Treatment includes vaccination,
antibiotic therapy, immunoglobulin replacement and surgery.
PMID- 27500814
TI - II. THE COGNITIVE DYNAMICS THEORY OF VISUAL WORKING MEMORY.
PMID- 27500815
TI - III. EMPIRICAL TESTS OF PREDICTIONS COMPARING CAPACITY ESTIMATES ACROSS TASKS AND
DEVELOPMENT.
PMID- 27500816
TI - IV. MODEL SIMULATIONS TESTING THE REAL-TIME STABILITY HYPOTHESIS OF DEVELOPMENTAL
CHANGES IN VISUAL WORKING MEMORY.
PMID- 27500817
TI - V. NEW QUESTIONS AND REMAINING CHALLENGES TO ACCOUNT FOR DEVELOPMENTAL
IMPROVEMENTS IN VISUAL WORKING MEMORY.
PMID- 27500819
TI - EXPLORING THE POSSIBLE AND NECESSARY IN WORKING MEMORY DEVELOPMENT.
AB - This commentary considers Vanessa Simmering's monograph on a dynamic-systems
theoretical approach to understanding working memory development, with reference
to the past, present, and future. In the section on the past, I attempt to
provide a further historical context for the work, discussing from where it
stemmed and how it is unique. In a second section, I contemplate the purpose of
the present modeling. The aim of the monograph may be primarily to establish a
simple possible account of development based on neural connection strength and
dynamic principles; it should not be judged as a proposal of what is necessarily
true. Finally, in the section on the future, I suggest some phenomena that
dissociate performance levels from stability over time and, therefore, appear to
require modifications of the theory. Several suggestions are made as to where
further refinement of the modeling effort could lead.
PMID- 27500820
TI - The impact of cognitive challenges in major depression: the role of the primary
care physician.
AB - Nearly 1 in 5 Americans will struggle with major depression in their lives; some
will have recurring bouts. Recent psychiatric research has given new attention to
the prevalence of cognitive deficits in major depression and the impact such
deficits have on remission and overall life functioning. When depression is
partially treated i.e., leaving residual symptoms, patients have higher rates of
relapse and lower functional outcomes. Impaired cognitive functioning is a
frequent residual symptom, persisting in about 45% of patients even when
emotional symptoms have improved, and results in a disproportionate share of the
functional impairment, particularly in the workplace. Patients with depression
have disrupted circuitry in brain regions responsible for cognition and it is
therefore important to screen depressed patients for cognitive as well as
emotional symptoms. Cognitive dysfunction should be evaluated in every mood
disordered patient with validated self-report scales such as the Patient Health
Questionnaire-9 or the Beck Depression Inventory and objective measures of
cognitive function are also very very useful. Two easily administered tests are
the Trails B Test and the Digit Symbol Substitution Test. Each take less than two
minutes and measure working memory, executive function, and processing speed and
can track cognitive improvement in depressed patients. Treatment of cognitive
dysfunction in major depression is complicated by the 'serotonin conundrum':
SSRI's frequently do not treat to full remission, and can cause cognitive
blunting-actually adding to cognitive problems. Based on recent data including
results from a recently completed meta-analysis by McIntyre and colleagues, an
evidence-based algorithm for treating cognitive symptoms in depression is
presented. A hierarchy of antidepressants and augmentation strategies based on
the best available evidence is discussed. In conclusion, cognitive symptoms in
major depressive disorder have been recognized as a target of therapeutic
improvement by the FDA and have become a focus of clinical importance.
PMID- 27500821
TI - Facile synthesis of optical pH-sensitive molybdenum disulfide quantum dots.
AB - An effective fabrication of MoS2 quantum dots (QDs) has been developed using
alkali metal-intercalation and exfoliation. The obtained MoS2 QDs are monolayers
with a uniform lateral size of 4.26 +/- 0.96 nm, which exhibit distinct blue
fluorescence with a quantum yield of 2.28%, robust dispersibility, storage
stability and pH dependent optical properties.
PMID- 27500822
TI - beta1-Adrenergic receptor Arg389Gly polymorphism affects the antiarrhythmic
efficacy of flecainide in patients with coadministration of beta-blockers.
AB - OBJECTIVE: beta1-Adrenergic receptor (beta1-AR) stimulation modulates the
antiarrhythmic activities of sodium channel blockers. The beta1-AR Gly389 variant
shows a marked decrease in agonist-stimulated cyclic AMP production compared with
that of the wild-type Arg389 in vitro. We investigated whether the Arg389Gly
polymorphism affects the efficacy of flecainide, a typical sodium channel
blocker, in patients with or without coadministration of beta-blockers. METHODS:
The effects of the beta1-AR Arg389Gly polymorphism on the antiarrhythmic efficacy
of flecainide were compared between with and without coadministered beta-blockers
in 159 patients with supraventricular tachyarrhythmia. The antiarrhythmic
efficacy of flecainide was assessed for at least 2 months by evaluating
symptomatology, 12-lead ECGs, and Holter monitoring results. RESULTS: Genetic
differences in the antiarrhythmic efficacy of flecainide were observed in
patients with coadministration of beta-blockers. Tachyarrhythmia was well
controlled in 60% of Arg389-homozygotes, 30% of Gly389-heterozygotes, and 0% of
Gly389-homozygotes (P=0.001). In contrast, no difference in the antiarrhythmic
efficacy was observed among the three genotypes in the patients without
coadministration of beta-blockers (64, 70, and 60%, respectively). Heart rate in
tachyarrhythmia in patients treated with flecainide was significantly higher in
Gly389 carriers than in Arg389-homozygotes (P=0.013). CONCLUSION: The Gly389
polymorphism decreased the antiarrhythmic efficacy of flecainide when
coadministered with beta-blockers. The results indicate that the Arg389Gly
polymorphism may play an important role in predicting the efficacy of flecainide
in patients with coadministration of beta-blockers.
PMID- 27500824
TI - Electrochemical Etching and Characterization of Sharp Field Emission Points for
Electron Impact Ionization.
AB - A new variation of the drop-off method for fabricating field emission points by
electrochemically etching tungsten rods in a NaOH solution is described. The
results of studies in which the etching current and the molarity of the NaOH
solution used in the etching process were varied are presented. The investigation
of the geometry of the tips, by imaging them with a scanning electron microscope,
and by operating them in field emission mode is also described. The field
emission tips produced are intended to be used as an electron beam source for ion
production via electron impact ionization of background gas or vapor in Penning
trap mass spectrometry applications.
PMID- 27500823
TI - Nephrotoxin Microinjection in Zebrafish to Model Acute Kidney Injury.
AB - The kidneys are susceptible to harm from exposure to chemicals they filter from
the bloodstream. This can lead to organ injury associated with a rapid decline in
renal function and development of the clinical syndrome known as acute kidney
injury (AKI). Pharmacological agents used to treat medical circumstances ranging
from bacterial infection to cancer, when administered individually or in
combination with other drugs, can initiate AKI. Zebrafish are a useful animal
model to study the chemical effects on renal function in vivo, as they form an
embryonic kidney comprised of nephron functional units that are conserved with
higher vertebrates, including humans. Further, zebrafish can be utilized to
perform genetic and chemical screens, which provide opportunities to elucidate
the cellular and molecular facets of AKI and develop therapeutic strategies such
as the identification of nephroprotective molecules. Here, we demonstrate how
microinjection into the zebrafish embryo can be utilized as a paradigm for
nephrotoxin studies.
PMID- 27500825
TI - Diagnosis of Musculus Gastrocnemius Tightness - Key Factors for the Clinical
Examination.
AB - Common foot and ankle pathologies have been linked to isolated Musculus
gastrocnemius tightness (MGT). Various examination techniques have been described
to assess MGT. Still, a standardized examination procedure is missing. Literature
argues for weightbearing examination but the degree of knee flexion needed to
eliminate the restraining effect of the M. gastrocnemius on ankle dorsiflexion
(ADF) is unknown. This manuscript investigates the effect of knee flexion on
ankle dorsiflexion and provides a detailed description of a standardized
examination protocol. Examination on 20 healthy individuals revealed, that 20
degrees of knee flexion is sufficient to fully eliminate the influence of the M.
gastrocnemius on ADF. This builds the prerequisite for a standardized examination
for MGT. Non-weightbearing and weightbearing examination of ADF has to be
conducted with the knee fully extended and at least 20 degrees flexed. Two
investigators should conduct non-weightbearing testing with the subject in supine
position. In order to obtain reliable results, the axis of the fibula should be
marked. One examiner can conduct weightbearing examination with the subject in
lunge stance. Isolated MGT is present if ADF is impaired with the knee fully
extended and knee flexion results in a significant ADF increase. The herein
presented standardized examination is the prerequisite for future studies aiming
at establishing norm values.
PMID- 27500826
TI - Truncation and Mutation of a Transferrin Receptor Aptamer Enhances Binding
Affinity.
AB - Aptamers are proving their utility in a number of applications. However, to be
easily functionalized, their structure needs to be simplified. Therefore, we
sought to truncate a 50-nucleotide aptamer specific to the transferrin receptor
to its smallest functional unit using rational engineering of the predicted two
dimensional structure of the longer parent sequence. In addition, mutations were
introduced into the binding loop to determine their effect on the selectivity of
the aptamers. These base mutations enhanced the binding affinity of the aptamer,
while retaining its specificity. The equilibrium dissociation constant (Kd) was
reduced sixfold following the substitution of all four bases in the binding
region. In addition, these aptamers were efficiently internalized into
transferrin receptor-positive cells in a similar manner to the transferrin
receptor antibody and demonstrated colocalization with this antibody. This study
has shown that the smallest functional unit of this aptamer was 14 nucleotides.
This small size will be advantageous for future applications, such as drug
delivery or functionalization of other therapeutic modalities.
PMID- 27500827
TI - Continuous electroencephalography in pediatric traumatic brain injury: Seizure
characteristics and outcomes.
AB - BACKGROUND: Traumatic brain injury (TBI) is a major cause of pediatric morbidity
and mortality. Secondary injury that occurs as a result of a direct impact plays
a crucial role in patient prognosis. The guidelines for the management of severe
TBI target treatment of secondary injury. Posttraumatic seizure, one of the
secondary injury sequelae, contributes to further damage to the injured brain.
Continuous electroencephalography (cEEG) helps detect both clinical and
subclinical seizure, which aids early detection and prompt treatment. OBJECTIVE:
The aim of this study was to examine the relationship between cEEG findings in
pediatric traumatic brain injury and neurocognitive/functional outcomes. METHODS:
This study focuses on a subgroup of a larger prospective parent study that
examined children admitted to a level-1 trauma hospital. The subgroup included
sixteen children admitted to the pediatric intensive care unit (PICU) who
received cEEG monitoring. Characteristics included demographics, cEEG reports,
and antiseizure medication. We also examined outcome scores at the time of
discharge and 4-6weeks postdischarge using the Glasgow Outcome Scale - Extended
Pediatrics and center-based speech pathology neurocognitive/functional evaluation
scores. RESULTS: Sixteen patients were included in this study. Patients with
severe TBI made up the majority of those that received cEEG monitoring.
Nonaccidental trauma was the most frequent TBI etiology (75%), and subdural
hematoma was the most common lesion diagnosed by CT scan (75%). Fifteen patients
received antiseizure medication, and levetiracetam was the medication of choice.
Four patients (25%) developed seizures during PICU admission, and 3 patients had
subclinical seizures that were detected by cEEG. One of these patients also had
both a clinical and subclinical seizure. Nonaccidental trauma was an etiology of
TBI in all patients with seizures. Characteristics of a nonreactive pattern,
severe/burst suppression, and lack of sleep architecture, on cEEG, were
associated with poor neurocognitive/functional outcome. CONCLUSION: Continuous
electroencephalography demonstrated a pattern that associated seizures and poor
outcomes in patients with moderate to severe traumatic brain injury, particularly
in a subgroup of patients with nonaccidental trauma. Best practice should include
institution-based TBI cEEG protocols, which may detect seizure activity early and
promote outcomes. Future studies should include examination of individual cEEG
characteristics to help improve outcomes in pediatric TBI.
PMID- 27500828
TI - Stability and Biological Activity Evaluation of Chlorantraniliprole Solid
Nanodispersions Prepared by High Pressure Homogenization.
AB - Poorly water-soluble compounds are difficult to develop as pesticide products and
face great challenges in water-based and environmentally friendly formulation
development. In this study, high pressure homogenization combined with
lyophilization was adopted to prepare the solid nanodispersions of
chlorantraniliprole with poor solubility and high melting point. The mean
particle sizes of the solid nanodispersions with different pesticide contents
were all less than 75 nm, even when the content was up to 91.5%. For the 2.5%
chlorantraniliprole solid nanodispersion with the mean particle size of 29 nm,
the suspensibility and wetting time in water were 97.32% and 13 s, respectively.
The re-dispersibility and wettability were superior to those of conventional
water dispersible granules. The retention on the rice leaf of 18.7 mg/cm2 was 1.5
and 3 times that of commercial aqueous suspension concentrate and pure water. The
bioassay result to diamondback moths indicated that the toxicity of the solid
nanodispersion was 3.3 and 2.8 times that of technical and aqueous suspension
concentrate, respectively. Moreover, the solid nanodispersion has the advantages
of total avoidance of organic solvents, significant reduction of surfactants and
feasibility of obtaining high concentration nanoformulations. The solid
nanodispersion is an attractive candidate for improving pesticide solubility and
efficacy, and its application in crop production will reduce both residues in
food and environmental pollution of pesticide.
PMID- 27500830
TI - Erratum: Immunodiagnostic Tests' Predictive Values for Progression to
Tuberculosis in Transplant Recipients: A Prospective Cohort Study: Erratum.
AB - [This corrects the article DOI: 10.1097/TXD.0000000000000520.].
PMID- 27500829
TI - The Discrete Emotions Questionnaire: A New Tool for Measuring State Self-Reported
Emotions.
AB - Several discrete emotions have broad theoretical and empirical importance, as
shown by converging evidence from diverse areas of psychology, including facial
displays, developmental behaviors, and neuroscience. However, the measurement of
these states has not progressed along with theory, such that when researchers
measure subjectively experienced emotions, they commonly rely on scales assessing
broad dimensions of affect (positivity and negativity), rather than discrete
emotions. The current manuscript presents four studies that validate a new
instrument, the Discrete Emotions Questionnaire (DEQ), that is sensitive to eight
distinct state emotions: anger, disgust, fear, anxiety, sadness, happiness,
relaxation, and desire. Emotion theory supporting the importance of
distinguishing these specific emotions is reviewed.
PMID- 27500831
TI - Male Smokers' and Non-Smokers' Response Inhibition in Go/No-Go Tasks: Effect of
Three Task Parameters.
AB - Impaired response inhibition plays a major role in many addictive behaviors.
However, in studies using go/no-go tasks, findings regarding the presence of
response inhibition deficits in nicotine-dependent individuals are mixed. This
might be due to differences between studies on a number of task parameters. Here
we aimed to identify task conditions under which go/no-go task performance
deficits can be observed in smokers and to characterize the nature of such
deficits. Sixty-one male students (30 smokers, 31 non-smokers) performed a go/no
go task while independently manipulating three task parameters: (1) percentage no
go trials (50% or 25%), (2) stimulus presentation time (600 ms or 200 ms), and
(3) nature of no-go stimuli (cigarette related or cigarette unrelated). Three
measures, reaction time on go trials and percentage correct responses on go and
no-go trials, served as performance indicators. Under 200-ms but not 600-ms
stimulus presentation conditions, the smokers responded faster on go trials and
made more errors on both go and no-go trials than the non-smokers did. These
differences occurred irrespective of the percentage of no-go trials and nature of
no-go stimuli. The accuracy differences disappeared after controlling for the
response time differences, suggesting a strong speed-accuracy trade-off. This
study contributes to unraveling the conditions under which smokers display
impaired inhibition performance and helps to characterize the nature of this
impairment. Under task conditions prompting fast responding, smokers are more
prone to increase response speed and to make more errors than non-smokers.
PMID- 27500832
TI - Re-interventions after TEVAR for type B aortic dissection: considerations for
management and the need for further insight.
PMID- 27500834
TI - Is the Combination of Insecticide and Mating Disruption Synergistic or Additive
in Lightbrown Apple Moth, Epiphyas postvittana?
AB - Pest suppression from combinations of tactics is fundamental to pest management
and eradication. Interactions may occur among tactical combinations and affect
suppression. The best case is synergistic, where suppression from a combination
is greater than the sum of effects from single tactics (AB >> A+B). We explored
how mating disruption and insecticide interacted at field scale, additively or
synergistically. Use of a pheromone delivery formulation (SPLATTM) as either a
mating disruption treatment (i.e. a two-component pheromone alone) or as a lure
and kill treatment (i.e. the two-component pheromone plus a permethrin
insecticide) was compared for efficacy against the lightbrown apple moth Epiphyas
postvittana. Next, four point-source densities of the SPLATTM formulations were
compared for communication disruption. Finally, the mating disruption and lure
and kill treatments were applied with a broadcast insecticide. Population
assessment used virgin female traps and synthetic pheromone in replicated 9-ha
vineyard plots compared with untreated controls and insecticide-treated plots, to
investigate interactions. Lure and kill and mating disruption provided equivalent
suppression; no additional benefit accrued from including permethrin with the
pheromone suggesting lack of contact. The highest point-source density tested
(625/ha) was most effective. The insect growth regulator methoxyfenoxide applied
by broadcast application lowered pest prevalence by 70% for the first ten weeks
compared to pre-trial. Pheromone addition suppressed the pest further by an
estimated 92.5%, for overall suppression of 97.7% from the treatment combination
of insecticide plus mating disruption. This was close to that expected for an
additive model of interactivity between insecticide and mating disruption (AB =
A+B) estimated from plots with single tactics as 98% suppression in a
combination. The results indicate the need to examine other tactical combinations
to achieve the potential cost-efficiencies of synergistic interactions.
PMID- 27500833
TI - Sirtuin-2 Regulates Sepsis Inflammation in ob/ob Mice.
AB - OBJECTIVE: Obesity increases morbidity and resource utilization in sepsis
patients. Sepsis transitions from early/hyper-inflammatory to late/hypo
inflammatory phase. Majority of sepsis-mortality occurs during the late sepsis;
no therapies exist to treat late sepsis. In lean mice, we have shown that
sirtuins (SIRTs) modulate this transition. Here, we investigated the role of
sirtuins, especially the adipose-tissue abundant SIRT-2 on transition from early
to late sepsis in obese with sepsis. METHODS: Sepsis was induced using cecal
ligation and puncture (CLP) in ob/ob mice. We measured microvascular inflammation
in response to lipopolysaccharide/normal saline re-stimulation as a "second-hit"
(marker of immune function) at different time points to track phases of sepsis in
ob/ob mice. We determined SIRT-2 expression during different phases of sepsis. We
studied the effect of SIRT-2 inhibition during the hypo-inflammatory phase on
immune function and 7-day survival. We used a RAW264.7 (RAW) cell model of sepsis
for mechanistic studies. We confirmed key findings in diet induced obese (DIO)
mice with sepsis. RESULTS: We observed that the ob/ob-septic mice showed an
enhanced early inflammation and a persistent and prolonged hypo-inflammatory
phase when compared to WT mice. Unlike WT mice that showed increased SIRT1
expression, we found that SIRT2 levels were increased in ob/ob mice during hypo
inflammation. SIRT-2 inhibition in ob/ob mice during the hypo-inflammatory phase
of sepsis reversed the repressed microvascular inflammation in vivo via
activation of endothelial cells and circulating leukocytes and significantly
improved survival. We confirmed the key finding of the role of SIRT2 during hypo
inflammatory phase of sepsis in this project in DIO-sepsis mice. Mechanistically,
in the sepsis cell model, SIRT-2 expression modulated inflammatory response by
deacetylation of NFkappaBp65. CONCLUSION: SIRT-2 regulates microvascular
inflammation in obese mice with sepsis and may provide a novel treatment target
for obesity with sepsis.
PMID- 27500835
TI - Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell
Receptor Retrogenic Mice.
AB - T cell receptor (TCR) signaling is essential in the development and
differentiation of T cells in the thymus and periphery, respectively. The vast
array of TCRs proves studying a specific antigenic response difficult. Therefore,
TCR transgenic mice were made to study positive and negative selection in the
thymus as well as peripheral T cell activation, proliferation and tolerance.
However, relatively few TCR transgenic mice have been generated specific to any
given antigen. Thus, studies involving TCRs of varying affinities for the same
antigenic peptide have been lacking. The generation of a new TCR transgenic line
can take six or more months. Additionally, any specific backcrosses can take an
additional six months. In order to allow faster generation and screening of
multiple TCRs, a protocol for retroviral transduction of bone marrow was
established with stoichiometric expression of the TCRalpha and TCRbeta chains and
the generation of retrogenic mice. Each retrogenic mouse is essentially a
founder, virtually negating a founder effect, while the length of time to
generate a TCR retrogenic is cut from six months to approximately six weeks. Here
we present a rapid and flexible alternative to TCR transgenic mice that can be
expressed on any chosen background with any particular TCR.
PMID- 27500837
TI - [Not Available].
PMID- 27500838
TI - [Not Available].
PMID- 27500836
TI - Control of Oocyte Reawakening by Kit.
AB - In mammals, females are born with finite numbers of oocytes stockpiled as
primordial follicles. Oocytes are "reawakened" via an ovarian-intrinsic process
that initiates their growth. The forkhead transcription factor Foxo3 controls
reawakening downstream of PI3K-AKT signaling. However, the identity of the
presumptive upstream cell surface receptor controlling the PI3K-AKT-Foxo3 axis
has been questioned. Here we show that the receptor tyrosine kinase Kit controls
reawakening. Oocyte-specific expression of a novel constitutively-active KitD818V
allele resulted in female sterility and ovarian failure due to global oocyte
reawakening. To confirm this result, we engineered a novel loss-of-function
allele, KitL. Kit inactivation within oocytes also led to premature ovarian
failure, albeit via a contrasting phenotype. Despite normal initial complements
of primordial follicles, oocytes remained dormant with arrested oocyte
maturation. Foxo3 protein localization in the nucleus versus cytoplasm explained
both mutant phenotypes. These genetic studies provide formal genetic proof that
Kit controls oocyte reawakening, focusing future investigations into the causes
of primary ovarian insufficiency and ovarian aging.
PMID- 27500839
TI - [Not Available].
PMID- 27500840
TI - [Not Available].
PMID- 27500841
TI - [Not Available].
PMID- 27500842
TI - [Not Available].
PMID- 27500843
TI - [Not Available].
PMID- 27500845
TI - [Not Available].
PMID- 27500844
TI - [Not Available].
PMID- 27500846
TI - [Not Available].
PMID- 27500847
TI - [Not Available].
PMID- 27500848
TI - [Not Available].
AB - The syndrome of overactive bladder (OAB) with the symptoms of frequency, urgency
and nocturia is often seen. After the diagnosis has been made by careful
exclusion of other conditions, there are different symptomatic treatment
strategies available. These include drug treatment as well as minimally invasive
local surgical treatments and treatments which intervene with the control of the
bladder by modulating central nervous areas. Alternative methods such as
acupuncture may help in individual cases; the placebo effect is high and there is
a lack of controlled studies.
PMID- 27500849
TI - [Physiotherapy in Women with Overactive Bladder].
AB - As regards treatment for overactive bladder, physiotherapeutic interventions can
be seen as an alternative to drug treatment. Targeted pelvic floor and bladder
training is used to decrease the number of voids and the incontinence episodes or
to increase the average voided volume in women with overactive bladder (3
systematic reviews with evidence level 1/1a).An additional option to treat women
with overactive bladder is to use functional electrical stimulation and magnetic
stimulation.2 systematic reviews 1 2 and 2 RCTs 3 4 reveal a low level of
evidence (2 studies with level 2/2b) for the use of electrical stimulation
(transcutaneous, vaginal or transanal) to reduce incontinence episodes and the
number of voids and to increase the average voided volume. The trial from
Yamanishi et al. (2014) shows that magnetic stimulation has a positive effect 5.
Further studies are needed to evaluate the benefit of conservative treatment
procedures for overactive bladder.
PMID- 27500850
TI - [Urethral Syndrome and Urethral Pain: Do we Treat People or Diagnoses?].
AB - The urethral syndrome with urethral pain and bladder voiding disorders is a
diagnosis of exclusion. Possible aetiologies are diverse and include organic,
functional and inflammatory pathologies of the urethra. Infections, inflammation
of the paraurethral glands, spasms of the sphincter muscle and/or of the pelvic
floor muscles, oestrogen deficiency, trauma, neuropathies, hypersensitivity and
psychosomatic issues have been investigated as possible causes.Patients with
urethral syndrome must be viewed, evaluated and treated holistically. They need a
lot of time and attention during their evaluation and treatment. It is now well
known that psychosocial aspects are involved in the development of many somatic
conditions and may have a crucial impact on the course of a disease. This needs
to be taken into consideration during the treatment process.
PMID- 27500851
TI - [Not Available].
PMID- 27500852
TI - Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in
targeted cancer therapy.
AB - As a result of the recent advances in molecular immunology, virology, genetics,
and cell processing, chimeric antigen receptor (CAR)-directed cancer therapy has
finally arrived for clinical application. CAR-directed adoptive immunotherapy
represents a novel form of gene therapy, cellular therapy, and immunotherapy, a
combination of three in one. Early phase clinical trial was reported in patients
with refractory chronic lymphoid leukemia with 17p deletion. Accompanying the
cytokine storm and tumor lysis syndrome was the shocking disappearance of the
leukemia cells refractory to chemotherapy and monoclonal antibodies. CAR therapy
was reproduced in both children and adults with refractory acute lymphoid
leukemia. The CAR technology is being explored for solid tumor therapy, such as
glioma. Close to 30 clinical trials are underway in the related fields
(www.clinicaltrials.gov). Further improvement in gene targeting, cell expansion,
delivery constructs (such as using Sleeping Beauty or Piggyback transposons) will
undoubtedly enhance clinical utility. It is foreseeable that CAR-engineered T
cell therapy will bring targeted cancer therapy into a new era.
PMID- 27500853
TI - The role of danger-associated molecular patterns (DAMPs) in trauma and
infections.
PMID- 27500854
TI - Diffusion Monte Carlo Perspective on the Spin-State Energetics of [Fe(NCH)6](2.).
AB - The energy difference between the high spin and the low spin state of the model
compound [Fe(NCH)6](2+) is investigated by means of Diffusion Monte Carlo (DMC),
where special attention is dedicated to analyzing the effect of the fix node
approximation on the accuracy of the results. For this purpose, we compare
several Slater-Jastrow and multireference Slater-Jastrow trial wave functions. We
found that a Slater-Jastrow trial wave function constructed with the generalized
Kohn-Sham orbitals from hybrid DFT represents the optimal choice. This is
understood by observing that hybrid functionals account for the subtle balance
between exchange and correlation effects and the respective orbitals accurately
describe the ligand-metal hybridization as well as the charge reorganization
accompanying the spin transition. Finally the DMC results are compared with those
obtained by Hartree-Fock, DFT, CASSCF, and CASPT2. While there is no clear
reference value for the high spin-low spin energy difference, DMC and high level
CCSD(T) calculations agree within around 0.3 eV.
PMID- 27500855
TI - Short-term effects of air temperature on plasma metabolite concentrations in
patients undergoing cardiac catheterization.
AB - BACKGROUND: Epidemiological studies have shown associations between air
temperature and cardiovascular health outcomes. Metabolic dysregulation might
also play a role in the development of cardiovascular disease. OBJECTIVES: To
investigate short-term temperature effects on metabolites related to
cardiovascular disease. METHODS: Concentrations of 45 acylcarnitines, 15 amino
acids, ketone bodies and total free fatty acids were available in 2869
participants from the CATHeterization GENetics cohort recruited at the Duke
University Cardiac Catheterization Clinic (Durham, NC) between 2001 and 2007. Ten
metabolites were selected based on quality criteria and cluster analysis. Daily
averages of meteorological variables were obtained from the North American
Regional Reanalysis project. Immediate, lagged, and cumulative temperature
effects on metabolite concentrations were analyzed using (piecewise) linear
regression models. RESULTS: Linear temperature effects were found for glycine,
C16-OH:C14:1-DC, and aspartic acid/asparagine. A 5 degrees C increase in
temperature was associated with a 1.8% [95%-confidence interval: 0.3%; 3.3%]
increase in glycine (5-day average), a 3.2% [0.1%; 6.3%] increase in C16-OH:C14:1
DC (lag of four days), and a -1.4% [-2.4%; -0.3%] decrease in aspartic
acid/asparagine (lag of two days). Non-linear temperature effects were observed
for alanine and total ketone bodies with breakpoint of 4 degrees C and 20 degrees
C, respectively. Both a 5 degrees C decrease in temperature on colder days (<4
degrees C)and a 5 degrees C increase in temperature on warmer days (>=4 degrees
C) were associated with a four day delayed increase in alanine by 6.6% [11.7;
1.8%] and 1.9% [0.3%; 3.4%], respectively. For ketone bodies we found immediate
(0-day lag) increases of 4.2% [-0.5%; 9.1%] and 12.3% [0.1%; 26.0%] associated
with 5 degrees C decreases on colder (<20 degrees C) days and 5 degrees C
increases on warmer days (>=20 degrees C), respectively. CONCLUSIONS: We observed
multiple effects of air temperature on metabolites several of which are reported
to be involved in cardiovascular disease. Our findings might help to understand
the link between air temperature and cardiovascular disease.
PMID- 27500856
TI - Synthesis of N-(2-Hydroxyaryl)benzotriazoles via Metal-Free O-Arylation and N-O
Bond Cleavage.
AB - A metal-free method for synthesis of N-(2-hydroxyaryl)benzotriazoles via O
arylation of N-hydroxybenzotriazoles with readily available diaryliodonium salts
and sequential N-O bond cleavage under mild conditions has been developed. The
[3,3]-rearrangement of N-O bond cleavage could take place on the N instead of C
atom. The reaction was compatible with diverse functional groups and a new type
of P,N-ligand was synthesized in three steps.
PMID- 27500857
TI - Intercomparison NaI(Tl) and HPGe spectrometry to studies of natural radioactivity
on geological samples.
AB - In this study, in situ gamma spectra using NaI(Tl) detector have been compared
with the laboratory measurements by using HPGe detector on geological samples.
The results for measuring naturally occurring terrestrial gamma radiation of 40K
and the decay series of 232Th and, 238U respectively of both detectors show a
maximum deviation about 5%. The mass activities series from both detectors were
checked for coherence using proficiency test procedure from the International
Atomic Energy Agency. The reliability and precision pass for final scores for all
the analytical determinations of are received "acceptable" for all radionuclides.
PMID- 27500858
TI - Analysis of the accumulation and redistribution patterns of cesium in Vicia faba
grown on contaminated soils.
AB - The aim of this study was to investigate the relationship between cesium (Cs)
contamination and plant growing stages in crops or vegetables grown on Cs
contaminated soils. Vicia faba was grown on Cs-contaminated soils under pot
culture conditions, and Cs uptake and bioaccumulation at various growing stages
were then measured. The results showed that Cs uptake by V. faba was
significantly greater on soils with a higher Cs content. As shown by the
bioaccumulation factor (BCF), the highest transfer coefficient occurred when V.
faba reached the maturation stage. Cs was easily transferred to young organs,
especially seeds, with an average percentage of 9.60% in seeds during the
maturation stage. This implies that Cs can be transferred to the human food chain
at all growth stages of the plant, especially the last stages. Uptake rates of Cs
remained stable during the generative growth phase of V. faba. This implies that
the cultivation of varieties with short generative growth periods can reduce Cs
accumulation in the edible parts of plants.
PMID- 27500859
TI - Probiotics, gut microbiota, and their influence on host health and disease.
AB - The gastrointestinal tract of mammals hosts a high and diverse number of
different microorganisms, known as intestinal microbiota. Many probiotics were
originally isolated from the gastrointestinal tract, and they were defined by the
Food and Agriculture Organization of the United Nations (FAO)/WHO as "live
microorganisms which when administered in adequate amounts confer a health
benefit on the host." Probiotics exert their beneficial effects on the host
through four main mechanisms: interference with potential pathogens, improvement
of barrier function, immunomodulation and production of neurotransmitters, and
their host targets vary from the resident microbiota to cellular components of
the gut-brain axis. However, in spite of the wide array of beneficial mechanisms
deployed by probiotic bacteria, relatively few effects have been supported by
clinical data. In this regard, different probiotic strains have been effective in
antibiotic-associated diarrhea or inflammatory bowel disease for instance. The
aim of this review was to compile the molecular mechanisms underlying the
beneficial effects of probiotics, mainly through their interaction with the
intestinal microbiota and with the intestinal mucosa. The specific benefits
discussed in this paper include among others those elicited directly through
dietary modulation of the human gut microbiota.
PMID- 27500860
TI - Multifunctional PLGA/Parylene C Coating for Implant Materials: An Integral
Approach for Biointerface Optimization.
AB - Functionalizing implant surfaces is critical for improving their performance. An
integrated approach was employed to develop a multifunctional implant coating
based on oxygen plasma-modified parylene C and drug-loaded, biodegradable poly(dl
lactide-co-glycolide) (PLGA). The key functional attributes of the coating (i.e.,
anti-corrosion, biocompatible, anti-infection, and therapeutic) were thoroughly
characterized at each fabrication step by spectroscopic, microscopic, and
biologic methods and at different scales, ranging from molecular, through the
nano- and microscales to the macroscopic scale. The chemistry of each layer was
demonstrated separately, and their mutual affinity was shown to be indispensable
for the development of versatile coatings for implant applications.
PMID- 27500862
TI - Organ boundary NAC-domain transcription factors are implicated in the evolution
of petal fusion.
AB - : Research rationale: Evolution of fused petals (sympetaly) is considered to be
an important innovation that has repeatedly led to increased pollination
efficiency, resulting in accelerated rates of plant diversification. Although
little is known about the underlying regulation of sympetaly, genetic pathways
ancestrally involved in organ boundary establishment (e.g. CUP SHAPED COTYLEDON
[CUC] 1-3 genes) are strong candidates. In sympetalous petunia, mutations in the
CUC1/2-like orthologue NO APICAL MERISTEM (NAM) inhibit shoot apical meristem
formation. Despite this, occasional 'escape shoots' develop flowers with extra
petals and fused inter-floral whorl organs. Central methods: To To determine if
petunia CUC-like genes regulate additional floral patterning, we used virus
induced silencing (VIGS) following establishment of healthy shoot apices to re
examine the role of NAM in petunia petal development, and uniquely characterise
the CUC3 orthologue NH16. KEY RESULTS: Confirming previous results, we found that
reduced floral NAM/NH16 expression caused increased petal-stamen and stamen
carpel fusion, and often produced extra petals. However, further to previous
results, all VIGS plants infected with NAM or NH16 constructs exhibited reduced
fusion in the petal whorl compared to control plants. MAIN CONCLUSIONS: Together
with previous data, our results demonstrate conservation of petunia CUC-like
genes in establishing inter-floral whorl organ boundaries, as well as functional
evolution to affect the fusion of petunia petals.
PMID- 27500861
TI - Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian
Rhythm Sleep-Wake Disorders.
AB - Circadian rhythm sleep-wake disorders (CRSWDs) are characterized by persistent or
recurrent patterns of sleep disturbance related primarily to alterations of the
circadian rhythm system or the misalignment between the endogenous circadian
rhythm and exogenous factors that affect the timing or duration of sleep. These
disorders collectively represent a significant unmet medical need, with a total
prevalence in the millions, a substantial negative impact on quality of life, and
a lack of studied treatments for most of these disorders. Activation of the
endogenous melatonin receptors appears to play an important role in setting the
circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore,
melatonin agonists, which may be able to shift and/or stabilize the circadian
phase, have been identified as potential therapeutic candidates for the treatment
of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is
approved for the treatment of a CRSWD: non-24-hour sleep-wake disorder (or non
24). However, three additional commercially available melatonin receptor agonists
agomelatine, prolonged-release melatonin, and ramelteon-have been investigated
for potential use for treatment of CRSWDs. Data indicate that these melatonin
receptor agonists have distinct pharmacologic profiles that may help clarify
their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic
properties of these melatonin agonists and summarize their efficacy profiles when
used for the treatment of CRSWDs. Further studies are needed to determine the
therapeutic potential of these melatonin agonists for most CRSWDs.
PMID- 27500863
TI - The impact of critical care transition programs on outcomes after intensive care
unit (ICU) discharge: can we get there from here?
PMID- 27500864
TI - Stretchable Multichannel Electromyography Sensor Array Covering Large Area for
Controlling Home Electronics with Distinguishable Signals from Multiple Muscles.
AB - Physiological signals provide important information for biomedical applications
and, more recently, in the form of wearable electronics for active interactions
between bodies and external environments. Multiple physiological sensors are
often required to map distinct signals from multiple points over large areas for
more diverse applications. In this paper, we present a reusable, multichannel,
surface electromyography (EMG) sensor array that covers multiple muscles over
relatively large areas, with compliant designs that provide different levels of
stiffness for repetitive uses, without backing layers. Mechanical and electrical
characteristics along with distinct measurements from different muscles
demonstrate the feasibility of the concept. The results should be useful to
actively control devices in the environment with one array of wearable sensors,
as demonstrated with home electronics.
PMID- 27500865
TI - Longitudinal clinical score prediction in Alzheimer's disease with soft-split
sparse regression based random forest.
AB - Alzheimer's disease (AD) is an irreversible neurodegenerative disease and affects
a large population in the world. Cognitive scores at multiple time points can be
reliably used to evaluate the progression of the disease clinically. In recent
studies, machine learning techniques have shown promising results on the
prediction of AD clinical scores. However, there are multiple limitations in the
current models such as linearity assumption and missing data exclusion. Here, we
present a nonlinear supervised sparse regression-based random forest (RF)
framework to predict a variety of longitudinal AD clinical scores. Furthermore,
we propose a soft-split technique to assign probabilistic paths to a test sample
in RF for more accurate predictions. In order to benefit from the longitudinal
scores in the study, unlike the previous studies that often removed the subjects
with missing scores, we first estimate those missing scores with our proposed
soft-split sparse regression-based RF and then utilize those estimated
longitudinal scores at all the previous time points to predict the scores at the
next time point. The experiment results demonstrate that our proposed method is
superior to the traditional RF and outperforms other state-of-art regression
models. Our method can also be extended to be a general regression framework to
predict other disease scores.
PMID- 27500866
TI - The presence of heterogeneous nuclear ribonucleoproteins in frontotemporal lobar
degeneration with FUS-positive inclusions.
AB - Frontotemporal lobar degeneration with fused in sarcoma-positive inclusions (FTLD
FUS) is a disease with unknown cause. Transportin 1 is abundantly found in FUS
positive inclusions and responsible for the nuclear import of the FET proteins of
which FUS is a member. The presence of all FET proteins in pathological
inclusions suggests a disturbance of transportin 1-mediated nuclear import. FUS
also belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) protein
family. We investigated whether hnRNP proteins are associated with FUS pathology
implicating dysfunctional nuclear export in the pathogenesis of FTLD-FUS. hnRNP
proteins were investigated in affected brain regions in FTLD-FUS using
immunohistochemistry, biochemical analysis, and the expression analysis. We
demonstrated the presence of several hnRNP proteins in pathological inclusions
including neuronal cytoplasmic inclusions and dystrophic neurites. The
biochemical analysis revealed a shift in the location of hnRNP A1 from the
nucleus to the cytoplasm. The expression analysis revealed an increase in several
hnRNP proteins in FTLD-FUS. These results implicate a wider dysregulation of
movement between intracellular compartments, than mechanisms only affecting the
nuclear import of FUS proteins.
PMID- 27500869
TI - [Wernicke-Korsakoff syndrome].
AB - AIM: To study the diagnosis and treatment of non-alcoholic Wernicke-Korsakoff
syndrome (WKS). MATERIAL AND METHODS: Eight patients (5 men and 3 women), mean
age 38,9+/-1,4 years, with WKS developed due to acute gastrointestinal tract
(GIT) disease (3 patients), the exacerbation of chronic GIT disease with
malabsorption (2 patients) and after surgery on the upper GIT (3 patients) were
included in the study. RESULTS: The disease manifested with consciousness
disturbance, symptoms of ataxia, eye movement disorders and bulbar syndrome that
developed after 24-48 h. Treatment resistant tonic-clonic seizures were developed
in 1 patient. MRI revealed hyper intensive signals on T2-weighted images in the
hypothalamus, mamillar bodies, brain stem, hippocampus as well as contrast
accumulation in the mamillar bodies. Treatment with vitamin B complex (neurobion)
and thiamine exerted a positive effect. CONCLUSION: Patients with GIT disease
with malabsorption are at risk of WKS. Consciousness disturbance, symptoms of
ataxia, eye movement disorders indicate the necessity of treatment with thiamine
that allows to prevent the development of stable cognitive deficit.
PMID- 27500870
TI - [The strategies for psychological self-control of seizures in patients with focal
epilepsy].
AB - AIM: To investigate self-control strategies for epileptic seizures and their
relationship to the individual coping-style in patients with focal epilepsy.
MATERIAL AND METHODS: Twenty one adult patients with focal epilepsy were
examined. Strategies for seizure control and coping-style were estimated with the
CBES-SC and the Brief COPE scale, respectively. The control group consisted of 20
healthy individuals. RESULTS: 86% of patients tried to control their seizures.
Most of the patients (33%) preferred to use behavioral self-management
strategies, which reduced the consequences of seizure. Patients with the high
self-control activity more often had adaptive problem-focused coping-style in
comparison to the patients with the low self-control (p<0.01). CONCLUSION: The
psychological coping-style modifying support can motivate patient to the wider
use of strategies for seizure control and improve a psychosocial adjustment of
the patient.
PMID- 27500871
TI - [The cholinergic deficiency syndrome in patients with depressed consciousness
after severe brain injury].
AB - AIM: To determine the clinical and electrophysiological (EEG) signs of
cholinergic deficiency in the process of recovery of consciousness in patients
with severe brain injury. MATERIAL AND METHODS: Thirty-seven people (24 men and
13 women, mean age 32+/-14 years) were studied. A comprehensive study included
assessment of neurological status, mental activity, and EEG. RESULTS AND
CONCLUSION: A set of neurological symptoms, including reduced muscle tone,
autonomic disorders (dry mucous membranes and skin, tachycardia, hypotension,
gastrointestinal tract), eye movement disorders, that were,in accordance with the
literature, characteristicof the cholinergic deficiency syndrome was found. This
syndrome was detected against the background of a comatose state, akinetic mutism
and mutism with understanding of speech, disintegration of speech, disorientation
and amnestic decline. EEG revealed stable over time (months) characteristic
changes: slowing and asymmetric alpha activity, equivalent dipole sources of
hippocampal and stem localization, persistent strengthening of intra-hemispheric
coherent connections, especially on the left side. The regression of the
cholinergic deficiency syndrome was accompanied by an increase of regularity,
capacity and frequency of alpha-activity (from 7-8 to 9-10 Hz), prevalence of
equivalent dipole sources in the hippocampus with their appearance in the
occipital cortex, normalization of connections with right-brain coherence with
the preservation of their pathologically high values on the left side.
PMID- 27500872
TI - [Possibilities of treatment optimization in children and adolescents with
epilepsy and disturbances of emotion and volition (disphoria)].
AB - AIM: To optimize the treatment of dysphoriain children and adolescents in regard
to sex and disease severity. MATERIAL AND METHODS: Seventy children and
adolescents (boys - 45, girls - 25), aged from 6 to 18 years, with different
forms of epilepsy and emotion and dysphoric disturbances were studied using CPRS
andGCIscales Depending on dysphoria severity, patients were stratified into three
groups: mild (n=19 (27.1%), moderate (n=27 (38.6%)) and severe (n=24 (34.3%)).
RESULTS AND CONCLUSION: Dysphoric disorders were significantly more prevalent in
boys, hostility and aggression were characteristic of boys as well. These facts
impactedtreatment options. Neuroleptics were more frequently used in boys (35.5%)
compared to girls(16%).Mild dysphoria didn't require additional treatment besides
AED in 78,4%. In 75% cases of moderate dysphoria,systemic treatment with
neuroleptics for 6 months was necessary. One-time recommendations for neuroleptic
treatment were made in all three groups with the prevalence in a groupof children
with severe and moderate dysphoria.
PMID- 27500873
TI - [A randomized single blind study of the efficacy of pregabalin in the treatment
of opioid withdrawal syndrome].
AB - AIM: To study the efficacy and safety of pregabalin (lyrica) in the complex
treatment of opioid withdrawal syndrome (OWS). MATERIAL AND METHODS: STUDY
DESIGN: single-blind randomized symptom-triggered protocol with an active
control. Thirty-four patients were randomly assigned to two groups. The first
group (n=19) received up to 600 mg a day of pregabalin for six days along with
symptomatic therapy (basic and symptom-triggered). The second group (n=15)
received up to 600 micrograms of clonidine a day as the main treatment along with
the same basic and symptomatic regimen. Opiate withdrawal severity, craving,
sleep disturbance, anxiety and depression, as well as general clinical
impressions and side-effects were assessed daily using internationally validated
quantitative psychometric instruments. RESULTS: In the pregabalin group, 15 out
of 19 (79%) patients completed treatment compared to 7 out of 15 (47%) patients
in the clonidine group (p=0.05; Fisher exact test). There were no statistically
significant differences between groups on any assessments of the severity of OWS
(reduction of the severity of opiate withdrawal), perhaps because of the small
sample size. In the pregabalin group, there were lower indicators of the severity
of craving for opiates (p=0.05), anxiety (p=0.05) and depression (p<0.05), while
patient-rated self-assessment of their general health condition was significantly
better compared to the second group (p<0.05). There were no significant
differences in the frequency of adverse events between the groups, though the
better tolerability of treatment was noted in the pregabalin group. CONCLUSION:
Treatment regimen of OWS with pregabalin is effective and safe and patients
tolerate it better that leads to a higher detoxification completion rate
(retention).
PMID- 27500874
TI - [Treatment of chronic cerebral venous insufficiency: a study on an effect of L
lysine aescinat].
AB - AIM: To study an effect of L-lysine aescinat on the dynamics of complaints,
severity of neurological syndromes and parameters of cerebral blood flow
estimated by transcranial doppler and duplex scanning in patients with chronic
cerebral venous insufficiency (CCVI). MATERIAL AND METHODS: Eighty patients with
ultrasound-confirmed CCVI were examined. The basic group included 40 patients who
received two treatment courses (intravenous drop-by-drop/stream introductions of
L-lysine aescinat in the dose of 5ml during 7 days in 2nd and 30th days of
examination). The comparison group consisted of 40 patients. RESULTS AND
CONCLUSION: Treatment with L-lysine aescinat led to the significant decrease in
complaints and improved the scores on the scales used in the study. There was an
improvement in the cerebral hemodynamics (an increase of hemodynamic reserve and
normalization of the linear blood flow velocity in deep veins) in the patients
with CCVI. The safe profile of L-lysine aescinat used in recommended doses was
confirmed.
PMID- 27500875
TI - [Linguistic adaptation of the Russian version of the Short-form McGill Pain
Questionnaire-2].
AB - AIM: Linguistic adaptation of the Russian version of the Short-form McGill Pain
Questionnaire-2 (SF-MPQ-2), which is conceptually equivalent to the original
questionnaire. MATERIAL AND METHODS: The adaptation of the Russian version of SF
MPQ-2 was performed in accordance to established rules in several stages by two
independent translators with the development of a consensus Russian version and
its back translation by two independent translators and development of a
consensus English version. The final Russian SF-MPQ-2 version was then created.
RESULTS AND CONCLUSION: The Russian version of the Short-form McGill Pain
Questionnaire-2 (SF-MPQ-2-RU) was generated based on the established rules. This
version was legally registered by the right holder - Mapi Research Trust and
recommended for research in the Russian Federation.
PMID- 27500876
TI - [An experimental in vitro study of antioxidant and antiradical properties of
cytoflavin, vinpocetine, actovegin and ethylmethylhydroxypyridine succinate].
AB - AIM: To investigate experimentally in vitro the antioxidant and anti-radical
activity of several drugs. MATERIAL AND METHODS: Antioxidant activity was
assessed by induced luminol-dependent chemiluminescence (CL). An impact on the
generation of reactive oxygen species (O2-, OH, 1D, H2O2, HClO) and their ability
to inhibit the auto-oxidation of quercetin combined with the generation of
superoxide radical anion were determined. Anti-radical activity was studied by
the method of restoring a stable radical alpha-alpha-diphenyl-beta-picryl
hydrazine (DPPH) molecule of the alleged anti-oxidant. RESULTS AND CONCLUSION:
The many-sided action of the drugs on the products of free radicals generated in
the in vitro experiments has been shown. Only cytoflavin has the highest total
antioxidant and antiradical activity. Vinpocetine has demonstrated similar, but
somewhat less pronounced, activity. Ethylmethylhydroxypyridine succinate and
actovegin have shown only the nonspecific superoxide dismutase activity which was
by times lower than that of cytoflavin and vinpocetine.
PMID- 27500877
TI - [Structural variations of the genome in autistic spectrum disorders with
intellectual disability].
AB - AIM: To analyze structural variations in the genome in children with autism and
intellectual disability. MATERIAL AND METHODS: Using high-resolution karyotyping
(AffymetrixCytoScan HD Array) and original bioinformatic technology, 200 children
with autism and intellectual disability were studied. RESULTS AND CONCLUSION:
Data on structural variations in the genome in children with autism and
intellectual disability are provided. Causative genomic pathology (chromosome
abnormalities and copy number variations - CNV) was determined in 97 cases
(48.5%). Based on these RESULTS: 24 candidate genes for autism with intellectual
disability were selected. In 16 cases (8%), the chromosome mosaicism manifested
as aneuploidy of whole autosomes and sex chromosomes (gonosomes) was identified.
In 87 children (43.5%), there were genomic variations, which are characteristic
of the so-called "grey zone" of genetic pathology in mental illnesses.
Bioinformatic analysis showed that these genomic variations had a pleiotropic
effect on the phenotype.
PMID- 27500878
TI - [An effect of quetiapine on the immune system of patients with schizophrenia].
AB - AIM: To study an effect of the atypical antipsychotic quetiapine on the immune
system of patients with schizophrenia with account for treatment efficacy.
MATERIAL AND METHODS: Quetiapine was administered to 27 patients diagnosed with
residual schizophrenia (F20.5) for 6 weeks in dose 200-400 mg/day; dynamic of
clinical symptoms was evaluated with PANSS i CGI scales before administration of
quetiapine and by week 6 of the treatment. Along with clinical assessments,
immune indices were determined. RESULTS: At the end of week 6 of treatment,
statistically significant changes of PANSS psychopathological symptoms were
noted. According to CGI scale, patients were divided into group 1 with high
treatment efficacy (n=17) and group 2 with the low efficacy (n=10). Significant
between-group differences before treatment were as follows: the decreased number
of lymphocytes of CD3+- CD16+-phenotypes, increased number of HLADR+-lymphocytes
and IgA level in group 2. The quetiapine therapy led to the positive dynamic of
phagocytosis indices, CD16+-lymphocytes, decrease in the level of IgA.
CONCLUSION: Possible predictors of treatment efficacy were found including the
number of mature T (CD3+) lymphocytes, CD16+ natural killers, HLADR+ lymphocytes
and IgA concentrations.
PMID- 27500879
TI - [Significance of sleep deprivation in the development of local epilepsy from
neuroplasticity opinion].
AB - AIM: Learning cycle "sleep-wake" is of great theoretical and practical importance
because it allows to understand the general patterns of adaptive mechanisms of
human interaction with the environment (neuroplasticity), violations of which are
the basis of many diseases of the CNS, including epilepsy. MATERIAL AND METHODS:
Complex clinical and electroencephalographic (video-EEG monitoring with mandatory
recording of sleep) study was carried out before and after prolonged sleep
deprivation (for at least 1 day) of 178 patients with locally due to epilepsy
(LEi). 45 healthy volunteers were examined in the control group as well as the
patients with epilepsy. The work was carried out to compare the results of
clinical and neurological and electrophysiological studies during sleep
deprivation (SD) in patients with LEi and in healthy individuals with
neurohistological and electron microscopic patterns of changes in the brain of
rats in an experiment with 48-hour SD. RESULTS AND CONCLUSION: Discovered in the
CNS of rats after SD morphological changes such as pleyokoniya of mitochondria,
damage in the blood-brain barrier, signs of exhaustion astrocytes, glial cells
and the change of the nuclei of gliocytes and some neurons of the type of
apoptosis and karyorrhexis and destruction of synapses reveal a violation of the
fundamental mechanisms of neuroplasticity. The results allow us to consider the
SD patients as a damaging factor for the central nervous system, provoking the
development of epileptic seizures and epilepsy, and the SD in laboratory animals
can be used as a model for further study of the mechanisms of neuroplasticity. In
addition the findings greatly complement current understanding of the mechanisms
of neuroplasticity and pathogenesis of epilepsy, and justify the need for the
study of therapeutic efficacy of modulators of neuroplasticity (transcranial
magnetic stimulation, ipidacrin etc.) in the complexe treatment of patients with
the this specified profile.
PMID- 27500880
TI - [A comparative analysis of multiple linear models of medical service satisfaction
among inpatients with borderline disorders at first-time admission and
rehospitalization].
AB - AIM: To find out the factors of satisfaction with psychiatric help in inpatients
with neurotic and depressive disorders depending on the moment of satisfaction
evaluation and patients' treatment experience. MATERIAL AND METHODS: The sample
included 266 first-time admission inpatients (satisfaction was evaluated at the
moment of discharge) and 134 rehospitalized inpatients (satisfaction with
previous treatment was evaluated at the moment of discharge; satisfaction with
current treatment was evaluated at the moment of rehospitalization). The survey
was performed using a questionnaire designed for this study. Statistical analysis
was performed using multiple regression. RESULTS AND CONCLUSION: Satisfaction
with nursing care was the key factor of satisfaction at the moment of discharge
among both groups of inpatients (first-time admission and rehospitalization).
Psychiatrist's empathy was the 2nd factor by importance. The structure of factors
of medical service satisfaction of these 2 groups was different. General
satisfaction with psychiatrist's work was the key factor of satisfaction with
medical service during previous hospitalization while nursing care was twice less
important. In whole, there were major differences in the structure of factors of
medical service satisfaction during previous and current hospitalizations. The
shift of importance from nursing care to psychiatrist's work and other
differences in the structure of factors of satisfaction of rehospitalized
patients with medical services can be explained by belonging of medical services
to credible goods - patient is able to evaluate results of treatment only some
period after discharge.
PMID- 27500881
TI - [Posterior reversible encephalopathy syndrome due to hypocalcemia: a description
of a case and an analysis of a pathogenic role of electrolyte disturbances].
AB - Afemale patient with recurrent posterior reversible encephalopathy syndrome,
severe hypocalcemia due to extirpation of the parathyroid glands is described.
The disease was characterized by the acute development of headache, seizures,
cognitive and behavioral disorders, mental confusion, transitory blood pressure
increasing. The vasogenic edema in the posterior parts of the brain, detected by
CT at the first exacerbation,was completely regressed. The residual neurological
deficit and MRI changes remained after the recurrent exacerbations. Main clinical
features of PRESare explained by hypocalcemia and accompanying electrolyte
disturbances.The reported case shows the necessity to study blood electrolytes in
patients with PRES to clarify their pathogenic role and the necessity of drug
correction.
PMID- 27500882
TI - Robust Underwater Oil-Repellent Material Inspired by Columnar Nacre.
AB - Inspired by natural columnar nacre, artificial montmorillonite/hydroxyethyl
cellulose columnar nacre-like materials with a site-specific layered structure in
the interior and a hierarchical columnar structure on the surface are prepared.
The materials exhibit improved tensile strength, good chemical stability in
seawater, superior resistance to sand-grain impingement, and robust underwater
low-adhesive superoleophobicity.
PMID- 27500883
TI - Meningeal Ewing Sarcoma/Peripheral PNET: Clinicopathological, Immunohistochemical
and FISH study of four cases.
AB - Meningeal Ewing Sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET)
is a rare diagnostically challenging small round cell tumor in the CNS. This
study investigates the clinical pathological features of four cases of this tumor
from archives of 6 years in our hospital. Patients were within the median age of
21.5 years and male to female ratio was 1:1. The tumors distributed at the supra
tentorial location, posterior fossa and lumbar vertebral canal, usually
presenting as the dura-sited nodule or having close connection with the meninges
within the cranium or vertebral canal. Histopathologically, small round
undifferentiated tumor cells with hypercellularities, scant cytoplasm and
inconspicuous nucleoli were observed, although some components such as atypical
larger vesicular nuclei, prominent nucleoli of tumor cells, necrotic foci and
mesenchymal collagen proliferation forming the lobular structure, were also
appreciated. Immunohistochemally, tumor cells displayed membranous positivity of
CD99 (4/4), nuclear positivity of FLI-1 (4/4) and NKX2.2 (4/4), negativity of
EMA, GFAP and synaptophysin expression. The histochemical PAS staining showed
weak positivity in one case. Fluorescence in situ hybridization (FISH) test using
EWSR1 (22q12) dual color break apart rearrangement probe showed positive results
in two cases. Results suggest that using a panel of immunohistochemical markers,
including NKX2.2, CD99, FLI-1, EMA, GFAP and synaptophysin, combined with the
supplementary EWSR1 FISH test, helps to define the diagnosis of meningeal
ES/pPNET of CNS.
PMID- 27500884
TI - Histone acetyltransferase general control non-repressed protein 5 (GCN5) affects
the fatty acid composition of Arabidopsis thaliana seeds by acetylating fatty
acid desaturase3 (FAD3).
AB - Seed oils are important natural resources used in the processing and preparation
of food. Histone modifications represent key epigenetic mechanisms that regulate
gene expression, plant growth and development. However, histone modification
events during fatty acid (FA) biosynthesis are not well understood. Here, we
demonstrate that a mutation of the histone acetyltransferase GCN5 can decrease
the ratio of alpha-linolenic acid (ALA) to linoleic acid (LA) in seed oil. Using
RNA-Seq and ChIP assays, we identified FAD3, LACS2, LPP3 and PLAIIIbeta as the
targets of GCN5. Notably, the GCN5-dependent H3K9/14 acetylation of FAD3
determined the expression levels of FAD3 in Arabidopsis thaliana seeds, and the
ratio of ALA/LA in the gcn5 mutant was rescued to the wild-type levels through
the overexpression of FAD3. The results of this study indicated that GCN5
modulated FA biosynthesis by affecting the acetylation levels of FAD3. We provide
evidence that histone acetylation is involved in FA biosynthesis in Arabidopsis
seeds and might contribute to the optimization of the nutritional structure of
edible oils through epigenetic engineering.
PMID- 27500885
TI - The initial repair response of articular cartilage after mechanically induced
damage.
AB - The regenerative potential of articular cartilage (AC) defects is limited and
depends on defect size, biomechanical conditions, and age. Early events after
overloading might be predictive for cartilage degeneration in the long term.
Therefore, the present aim is to investigate the temporal response of cartilage
to overloading at cell, matrix, and tissue level during the first period after
mechanical overloading. In the present study, the effect of high loading (~8 MPa)
at a high rate (~14 MPa/s) at day 0 during a 9 day period on collagen damage,
gene expression, cell death, and biochemical composition in AC was investigated.
A model system was developed which enabled culturing osteochondral explants after
loading. Proteoglycan content was repeatedly monitored over time using MUCT,
whereas other evaluations required destructive measurements. Changes in matrix
related gene expressions indicated a degenerative response during the first 6 h
after loading. After 24 h, this was restored and data suggested an initial repair
response. Cell death and microscopic damage increased after 24 h following
loading. These degradative changes were not restored within the 9 day culture
period, and were accompanied by a slight loss of proteoglycans at the articular
surface that extended into the middle zones. The combined findings indicate that
high magnitude loading of articular cartilage at a high rate induces an initial
damage that later initiates a healing response that can probably not be retained
due to loss of cell viability. Consequently, the matrix cannot be restored in the
short term. (c) 2016 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res 35:1265-1273, 2017.
PMID- 27500886
TI - Phosphorescent Molecular Butterflies with Controlled Potential-Energy Surfaces
and Their Application as Luminescent Viscosity Sensor.
AB - We report precise manipulation of the potential-energy surfaces (PESs) of a
series of butterfly-like pyrazolate-bridged platinum binuclear complexes, by
synthetic control of the electronic structure of the cyclometallating ligand and
the steric bulkiness of the pyrazolate bridging ligand. Color tuning of dual
emission from blue/red, to green/red and red/deep red were achieved for these
phosphorescent molecular butterflies, which have two well-controlled energy
minima on the PESs. The environmentally dependent photoluminescence of these
molecular butterflies enabled their application as self-referenced luminescent
viscosity sensor.
PMID- 27500887
TI - Preclinical Assessment of Safety and Efficacy of Fluorescent Dye for Detecting
Dermal Injuries (the injuries were both abrasions and incision) in a Murine
Model.
AB - Objective documentation of tears and abrasions to the external genitalia after
sexual assault is an important part of the forensic examination. A 1% aqueous
solution of toluidine blue (TB) dye is often used to highlight injury, but the
dye can be difficult to see on dark skin. We evaluated a fluorescent dye for
detecting injuries on all skin colors in a relevant preclinical murine model. We
compared the ability of trained, blinded observers to detect unstained wounds and
wounds stained with 1% fluorescein sodium (FL) and with TB. We also evaluated the
cutaneous wound healing response after application of both dyes. The no-dye group
had significantly fewer (p < 0.05) true-positive identifications compared to all
the dye groups. No differences in effectiveness were detected between dye
treatments. All groups exhibited statistically similar healing rates. These
findings support the evaluation of fluorescein sodium in a future clinical study
with human subjects.
PMID- 27500888
TI - Implications of Variation in the Relationships between Beneficiary
Characteristics and Medicare Advantage CAHPS Measures.
AB - OBJECTIVE: To study how differences in quality score adjustments across Medicare
Advantage contracts change comparisons for individuals and contracts. DATA
SOURCES: Responses to the Medicare Advantage implementation of the Consumer
Assessments of Healthcare Providers and Systems (CAHPS) survey from 2010 to 2014.
STUDY DESIGN: We fit national-and state-level hierarchical models to predict
CAHPS scores for individuals and contracts, adjusted for self-reported education,
general health, and mental health. We allow the effects of these variables on
quality measures to vary across contracts with a hierarchical model. DATA
COLLECTION/EXTRACTION METHODS: We perform secondary data analysis. PRINCIPAL
FINDINGS: For average consumers, standard adjustment is sufficient to represent
variation in contract quality standardized to a common population. For people
with characteristics far from average, personalized reporting using their
characteristics and contract-specific coefficients can substantially change the
expected quality measures across contracts. This effect is stronger when
comparing among contracts within a state than across all contracts. CONCLUSIONS:
Customized reporting may help consumers select the best Medicare Advantage plan,
but policies should protect against unintended consequences.
PMID- 27500890
TI - Intranodal palisaded myofibroblastoma - a rare case report and literature review.
AB - Intranodal palisaded myofibroblastoma (IPM) is a benign mesenchymal neoplasm
originating from smooth muscle cells and myofibroblasts. The inguinal region is
the most common site of this rare tumor. As there are only about 89 such cases
reported in the literature, the precise etiology and pathogenesis have yet to be
explained adequately. It is characterized by spindle cells, amianthoid fibers,
and by the proliferation of hemosiderin-containing histiocytes in the lymph node.
A nodular lesion was excised from the inguinal region of a 47-year-old female
patient with the clinical diagnosis of lymphoma and/or metastase. Macroscopic
examination of a section of the lesion demonstrated a solid appearance.
Microscopic examination revealed spindle-cell proliferation, amianthoid fibers,
hemosiderin pigment, and extravasated erythrocytes. Nuclei of the spindle cells
displayed a palisaded appearance. Compressed lymphoid tissue was observed around
the lesion. Neoplastic cells were identified by the presence of vimentin, SMA,
Cyclin D1, and beta-catenin. The Ki67 index was less than 1%. Histological
examination confirmed the diagnosis of IPM. Although IPM is benign, it is
frequently confused with metastatic lesions and lymphomas.
PMID- 27500891
TI - Current trends in topical therapies for chronic rhinosinusitis: update and
literature review.
AB - INTRODUCTION: Chronic rhinosinusitis (CRS) affects millions of patients
worldwide. The disease is multifactorial with influences including anatomic
factors, immunological disturbances, and altered sinonasal microbiome. Although
oral medications are effective in controlling some symptoms, they are associated
with side effects and long-term use is not ideal. Thus, topical therapies have
emerged as an alternative delivery method for localized, high-concentration
medication with less side effects. Areas covered: This is a review of the various
topical therapies available or under investigation for the management of CRS.
Common medications such as saline, steroids, and antimicrobials will be
discussed. Furthermore, additives including manuka honey, xylitol, surfactant, N
chlorotaurine, Dead Sea salt, and sodium hyaluronate will be addressed.
Innovations in topical therapies, such as drug-eluting biomaterials and
photodynamic therapy, will also be reviewed. Expert opinion: Although topical
therapies provide a high dose of active substance at the site of disease, their
efficacy in CRS is not clear. Topical saline and intranasal steroids appear to
consistently demonstrate therapeutic benefits. However, other topical medications
require further investigation to determine long-term clinical efficacy and
safety. A better understanding of their effects on the sinonasal mucociliary
system is needed before they become the standard of care in CRS.
PMID- 27500889
TI - Development of a Multicellular Three-dimensional Organotypic Model of the Human
Intestinal Mucosa Grown Under Microgravity.
AB - Because cells growing in a three-dimensional (3-D) environment have the potential
to bridge many gaps of cell cultivation in 2-D environments (e.g., flasks or
dishes). In fact, it is widely recognized that cells grown in flasks or dishes
tend to de-differentiate and lose specialized features of the tissues from which
they were derived. Currently, there are mainly two types of 3-D culture systems
where the cells are seeded into scaffolds mimicking the native extracellular
matrix (ECM): (a) static models and (b) models using bioreactors. The first
breakthrough was the static 3-D models. 3-D models using bioreactors such as the
rotating-wall-vessel (RWV) bioreactors are a more recent development. The
original concept of the RWV bioreactors was developed at NASA's Johnson Space
Center in the early 1990s and is believed to overcome the limitations of static
models such as the development of hypoxic, necrotic cores. The RWV bioreactors
might circumvent this problem by providing fluid dynamics that allow the
efficient diffusion of nutrients and oxygen. These bioreactors consist of a
rotator base that serves to support and rotate two different formats of culture
vessels that differ by their aeration source type: (1) Slow Turning Lateral
Vessels (STLVs) with a co-axial oxygenator in the center, or (2) High Aspect
Ratio Vessels (HARVs) with oxygenation via a flat, silicone rubber gas transfer
membrane. These vessels allow efficient gas transfer while avoiding bubble
formation and consequent turbulence. These conditions result in laminar flow and
minimal shear force that models reduced gravity (microgravity) inside the culture
vessel. Here we describe the development of a multicellular 3-D organotypic model
of the human intestinal mucosa composed of an intestinal epithelial cell line and
primary human lymphocytes, endothelial cells and fibroblasts cultured under
microgravity provided by the RWV bioreactor.
PMID- 27500892
TI - Buccally impacted maxillary canines increase the likelihood of root separation in
adjacent first premolars.
AB - OBJECTIVE: To investigate the influence of maxillary impacted canines on the root
morphology of adjacent premolars in a Chinese population. SUBJECTS AND METHODS: A
sample of 370 Chinese subjects with maxillary canine impaction and 370 control
subjects were collected in this study. CBCT data of all subjects were collected
and analyzed. The prevalence of separate-rooted maxillary premolars was compared
between subjects with and without impacted canines. Then, the prevalence of
separate-rooted maxillary premolars was compared between subjects with buccal
canine impaction (BIC) and those with palatal impaction (PIC). RESULTS: The
prevalence of separate-rooted first premolars was significantly higher in the
canine impaction group (P = 0.046), but the prevalence of separate-rooted second
premolars was not different (P = 0.780). Furthermore, a significant higher
prevalence of first premolar root separation was found on the impacted site in
the BIC subgroup (P < 0.001), but not in the PIC subgroup (P = 0.508). Also, the
prevalence of separate-rooted first premolars in the BIC subgroup was
significantly higher than that of the control group (P = 0.008), but not so for
the PIC subgroup (P = 0.097). CONCLUSIONS: Buccally impacted maxillary canines
are associated with an increased prevalence of root separation in the adjacent
maxillary first premolars. This is likely because that buccally impacted canines
encroach on the space needed for root development of the first premolars.
PMID- 27500893
TI - Appropriate fabrication method for vacuum-formed mouthguards.
AB - AIM: The aim was to examine the influence of the heating temperature on the
fabrication of vacuum-formed mouthguards. MATERIALS AND METHODS: Mouthguard
sheets of 3.8 mm ethylene vinyl acetate were vacuum-formed on working models at
three heating temperatures: 80, 100, and 120 degrees C. The thickness of the
mouthguard was measured at the labial surface of the central incisor, and the
buccal and occlusal surfaces of the first molar. Differences in the thickness of
the mouthguards were analyzed by two-way analysis of variance. The fit of the
mouthguard was examined at the central incisor and the first molar by measuring
the distance between the mouthguard and the cervical margin of the working model.
Differences in the distance between the mouthguard and the cervical margin
according to the heating temperatures were analyzed by one-way analysis of
variance. RESULTS: Mouthguard thickness varied among the measured regions of the
central incisors and first molars (P < 0.01). The greatest thickness was found at
the labial surface of the central incisor and the buccal surface of the first
molar in mouthguards fabricated with heating temperature of 120 degrees C (P <
0.05). The best fit was obtained in mouthguards fabricated with heating
temperature of 120 degrees C (P < 0.05). CONCLUSIONS: Heating the mouthguard
sheet until the temperature reached 120 degrees C was the best fabrication method
to maintain the thickness and to obtain proper fit. It is important to control
the heating temperature when fabricating vacuum-formed mouthguards.
PMID- 27500894
TI - Role of Clinical Pharmacology in the Development and Approval of Immunotherapies
Targeting Immune Checkpoints.
AB - Immune surveillance plays a critical role in preventing the development and
progression of cancer. Immune modulators, such as interferon-gamma or interleukin
2, have been a part of the cancer treatment armament over the past few decades.
However, new understandings regarding the role of the costimulatory and
coinhibitory molecules associated with T-cells and antigen-presenting cells as
well as tumor necrosis factor receptors and ligands have ushered the new era of
immunotherapy for cancer treatment. We now know that primary cancer cells evade
screening by the innate immune system, proliferate, and form metastases by
upregulating immune inhibitory pathways referred to as immune checkpoints. The
recent development of therapies that target immune checkpoints, such as cytotoxic
T lymphocyte antigen 4, programmed cell death 1, programmed cell death ligand 1,
indoleamine 2,3-dioxygenase, T-cell immunoglobulin and mucin domain 3, and
lymphocyte activation gene 3 precisely target the immune system and give new hope
for treating various types of cancer. In select marker-enriched populations,
immunotherapies provide high response rates as well as durable responses in terms
of progression-free survival and overall survival. Numerous factors, such as
patient's immune system, the expression of targets on both immune and cancer
cells, maintenance of an effective drug exposure, and tolerability to these
agents may play a role in this unique observation.
PMID- 27500895
TI - Half-century of Dental Public Health research: bibliometric analysis of world
scientific trends.
AB - OBJECTIVES: To describe the characteristics of Dental Public Health (DPH)
scientific publications within core DPH journals over time and to compare DPH
journals with DPH content from other journal types. METHODS: The Scopus database
was used to identify DPH-relevant articles published from 1965 to 2014 in three
core DPH journals (DPHJs) and from 2005 to 2014 in Dental Journals (DJs), Public
Health (PHJs) and General Journals (GJs). To identify DPH-relevant articles, a
search strategy with words about oral health and public health was applied to
each group of journals. Research themes were created by grouping similar keywords
to report changes in the focus of articles over time. The most productive
journals, countries, institutions and authors were also estimated for each set of
journals. RESULTS: In 2005-2014, 60 297 articles were identified, of which 2.7%
in DPHJs, 10.4% from PHJs, 38.2% from GJs and 48.7% from DJs. DPH-relevant
articles published in the core DPHJs, DJs and PHJs tended to share a strong
emphasis on dental caries, healthcare/services research on children and
adolescents. Over time, the focus in the DPHJs has increased towards health
behaviour/promotion/education, quality of life and socioeconomic factors. In the
last decade, those themes were more frequent in DPH journals than in the other
groups. CONCLUSIONS: DPH research published in DPHJs had some unique features and
greater focus on the themes of quality of life, socioeconomic factors and health
behaviour/education/promotion than other groups of journals.
PMID- 27500897
TI - The Microstructure of Cellulose Nanocrystal Aerogels as Revealed by Transmission
Electron Microscope Tomography.
AB - The microstructure of highly porous cellulose nanocrystal (CNC) aerogels is
investigated via transmission electron microscope (TEM) tomography. The aerogels
were fabricated by first supercritically drying a carboxylated CNC organogel and
then coating via atomic layer deposition with a thin conformal layer of Al2O3 to
protect the CNCs against prolonged electron beam exposure. A series of images was
then acquired, reconstructed, and segmented in order to generate a three
dimensional (3D) model of the aerogel. The model agrees well with theory and
macroscopic measurements, indicating that a thin conformal inorganic coating
enables TEM tomography as an analysis tool for microstructure characterization of
CNC aerogels. The 3D model also reveals that the aerogels consist of randomly
orientated CNCs that attach to one another primarily in three ways: end to end
contact, "T" contact, and "X" contact.
PMID- 27500896
TI - Combination of glycolic acid peel and topical 20% azelaic acid cream in melasma
patients: efficacy and improvement in quality of life.
AB - BACKGROUND: Glycolic acid (GA) peel is one of the most versatile agents in the
treatment of melasma. GA peeling alone or in combination with topical
hypopigmenting agents has shown encouraging results. However, there is paucity of
controlled trial demonstrating the efficacy of glycolic peel in conjunction with
topical azelaic acid (AA). We therefore sought to highlight the efficacy and
safety of this combination in melasma. OBJECTIVE: To assess the clinical
efficacy, safety and reduction in melasma quality of life (MELASQOL) scores on
combining serial GA peels with topical 20% AA cream in epidermal melasma.
MATERIALS AND METHOD: Sixty patients of epidermal melasma were enrolled for 24
weeks. Patients were divided into two groups: (1) Study group received serial GA
peel every 3 weeks with twice daily 20% AA cream, and (2) control group received
only 20% AA cream. Clinical improvement was assessed objectively using Melasma
Area Severity Index (MASI). Melasma-related quality of life was measured by
MELASQOL scale in both groups. Side effects were observed at each visit. RESULTS:
The improvement in MASI and percentage decrease in MASI scoring were
statistically significant 12 weeks onwards in study group as compared to control
group. There was also a significant reduction in MELASQOL scores in study group
as compared to control group after treatment. Minor reversible side effects were
observed in both groups, which did not require cessation of therapy. CONCLUSION:
GA peel enhances therapeutic efficacy of topical AA cream for treatment of
melasma, with improvement in quality of life without serious side effects.
PMID- 27500898
TI - National survey of nurse prescribing in mental health services; a follow-up 6
years on.
AB - WHAT IS KNOWN ON THE SUBJECT?: Nurse prescribing allows nurses, after specific
training, to prescribe medications under certain conditions. This article
describes the third in a series of surveys of mental health services in England
to understand how nurse prescribing is being used across the country. While there
is research evidence that shows nurse prescribing to be as safe as prescribing by
doctors and that service users typically find it at least as acceptable, there is
a lack of detailed evidence about current forms of nurse prescribing practice
specifically in mental health services. WHAT THIS PAPER ADDS TO EXISTING
KNOWLEDGE?: The survey found that the number of nurse prescribers has increased
over the last few years. Nurse prescribers are increasingly prescribing in a form
('independent prescribing') that makes them independently responsible for
prescribing decisions without working to a plan laid out by a doctor. Mental
health organisations are increasingly planning in a systematic way how to
identify, train and ensure good practice in nurse prescribing. This study
demonstrates that growth in numbers of nurse prescribers can take place over an
extended time period. The study demonstrates that the exact model of nurse
prescribing will influence its applicability in different types of service. WHAT
ARE THE IMPLICATIONS FOR PRACTICE?: Nurse prescribing is becoming increasingly
common in mental health services, changing roles for nurses and the experience of
services for service users. However, there is great variation between
organisations in this regard. Research is needed regarding the outcomes and any
risks of independent nurse prescribing specifically in mental health compared to
medical prescribing. ABSTRACT: Introduction This paper reports the latest in a
series of national surveys of nurse prescribing in mental health organizations in
England. Aim To describe and understand changes and trends in the use of nurse
prescribing nationally. Methods Postal survey to all 53 National Health Service
Mental Health Trusts (publicly funded provider organizations); 75% responded (n =
40). Results Numbers of nurse prescribers (NPs) have grown significantly in the
last 6 years, although remain a small percentage of the total Mental Health
Nursing workforce. Most NPs are in community services, particularly community
mental health teams and drug/alcohol services. Independent prescribing has now
become the most common form of NP, replacing supplementary prescribing.
Discussion Overall growth in numbers of NPs has continued, but remains marked by
large variance in numbers between organizations. The study evidences that the
particular form of nurse prescribing will influence its applicability in
different clinical settings and that sustained increase over time in NP numbers
is feasible at a national level, even with local variation in uptake.
Implications for practice Nurse prescribing has become well embedded in many
organizations although large-scale adoption may be hindered by the lack of a
definitive evidence base as to outcomes compared with those from medical
prescribing.
PMID- 27500899
TI - Clusters of landscape characters as a way of communication in characterisation: A
study from side, Turkey.
AB - Landscape is the natural and cultural features of the environment. Characters are
distinct recognisable patterns in the landscape that were comprised as a result
of human and nature interactions. Landscape characters demonstrate precise
features and values that exist in the current environment and provide information
for those who use, manage, live in, benefit from and enjoy the landscape. The aim
of this study was to interpret landscape characters with a common set of
terminology and to evaluate clusters of characters and so to discuss how they can
be used as a communicative tool in characterisation in the case of Side District
in Turkish Mediterranean. Number of 35 landscape characters were analysed as
variables with aesthetic, cultural, value, perceptual and natural features so to
communicate between characters and landscapes. The study results demonstrated
that clusters of landscape characters were divided into 3 character groups;
mainly cultural, mainly cultural and a joint cluster of aesthetic, and perceptual
and value aspects while spatial composition of landscape character groups was
named and mapped as natural, rural, historical, urban and buffer. Aesthetic
features were the most prominent elements as they combined in all sub-clusters
giving the evidence that landscape is a visual construct. However, landscape
characters which can be either outstanding or ordinary and their clusters provide
exchange of information about relationship between man and nature, natural and
cultural, objective and subjective for planners and managers, for public and
professionals. Landscape characters become a body of message which ultimately
offers a framework for planners and decision makers for both maintenance and
protection of landscapes.
PMID- 27500900
TI - Endometrial breakdown with sustained progesterone release involves NF-kappaB
mediated functional progesterone withdrawal in a mouse implant model.
AB - Irregular uterine bleeding is a major side effect of long-acting progestogen-only
contraceptives in women, and is the primary reason women discontinue their use.
In this study, a mouse model of endometrial breakdown was established using a
subcutaneous progesterone implant to understand how irregular bleeding begins.
Although progestogens sustained decidualization, endometrial breakdown was still
observed in this model. We, therefore, hypothesized that endometrial breakdown
might involve functional progesterone withdrawal. Using co-immunoprecipitation
assays, we observed the constitutive activation of nuclear factor kappa-b (NF
kappaB) p65 and its interaction with the progesterone receptor (PGR); moreover,
transcriptional activity of the PGR was also repressed by NF-kappaB activity in
primary mouse and human decidual stromal cells that mimic progesterone
maintenance. Yet the ratio of PGR-B to PGR-A was not increased in the mouse
model. In vivo comparison of endometrial breakdown induced by progesterone
withdrawal to that seen during sustained progesterone exposure, in the presence
of NF-kappaB inhibitors, revealed that NF-kappaB-mediated functional progesterone
withdrawal is involved in endometrial breakdown in this implant model. These data
prompt further studies to determine the homology of this functional progesterone
withdrawal mechanism in human endometrium. Mol. Reprod. Dev. 83: 780-791, 2016
(c) 2016 Wiley Periodicals, Inc.
PMID- 27500901
TI - Comparison of four validated psoriatic arthritis screening tools in diagnosing
psoriatic arthritis in patients with psoriasis (COMPAQ Study).
AB - BACKGROUND: Four validated psoriatic arthritis (PsA) screening tools are used for
diagnosing PsA in patients with psoriasis. OBJECTIVES: To evaluate the
sensitivity and specificity of the Toronto Psoriatic Arthritis Screen II (ToPAS
II), the Psoriatic Arthritis Screening and Evaluation (PASE), the Psoriasis
Epidemiology Screening Tool (PEST) and the Early Arthritis for Psoriatic Patients
(EARP) questionnaires in diagnosing PsA in patients with psoriasis. METHODS: This
was a noninterventional, cross-sectional study. In total, 302 patients with
psoriasis completed all the questionnaires prior to rheumatological evaluation.
Patients diagnosed as having a rheumatological disease were excluded.
Characteristics of joint involvement in PsA were noted, but details of non-PsA
rheumatological diseases were not captured. RESULTS: Of 302 patients with
psoriasis, 45 (14.9%) had PsA, according to the Classification of Psoriatic
Arthritis criteria; 27 (8.9%) had a ToPAS II score >= 8, suggestive of PsA; 36
(11.9%) had a PEST questionnaire score >= 3, suggestive of PsA; 50 (16.5%) had a
PASE questionnaire score >= 44 (PASE 44), suggestive of PsA; 47 (15.5%) had a
PASE score of 47 (PASE 47; used in development of the PASE questionnaire); and 72
(23.8%) patients had an EARP questionnaire score >= 3, suggestive of PsA. The
sensitivities and specificities of EARP, PASE 44, PASE 47, PEST and ToPAS II were
91%, 80%, 76%, 53% and 44%, and 88%, 95%, 95%, 95% and 97%, respectively.
CONCLUSIONS: EARP was found to have the best sensitivity; ToPAS II had the
highest specificity. A major limitation of the study design was the exclusion of
pre-existing rheumatological diseases.
PMID- 27500902
TI - Trabecular architecture in the thumb of Pan and Homo: implications for
investigating hand use, loading, and hand preference in the fossil record.
AB - OBJECTIVES: Humans display an 85-95% cross-cultural right-hand bias in skilled
tasks, which is considered a derived behavior because such a high frequency is
not reported in wild non-human primates. Handedness is generally considered to be
an evolutionary byproduct of selection for manual dexterity and augmented visuo
cognitive capabilities within the context of complex stone tool manufacture/use.
Testing this hypothesis requires an understanding of when appreciable levels of
right dominant behavior entered the fossil record. Because bone remodels in vivo,
skeletal asymmetries are thought to reflect greater mechanical loading on the
dominant side, but incomplete preservation of external morphology and ambiguities
about past loading environments complicate interpretations. We test if internal
trabecular bone is capable of providing additional information by analyzing the
thumb of Homo sapiens and Pan. MATERIALS AND METHODS: We assess trabecular
structure at the distal head and proximal base of paired (left/right) first
metacarpals using micro-CT scans of Homo sapiens (n = 14) and Pan (n = 9).
Throughout each epiphysis we quantify average and local bone volume fraction
(BV/TV), degree of anisotropy (DA), and elastic modulus (E) to address bone
volume patterning and directional asymmetry. RESULTS: We find a right directional
asymmetry in H. sapiens consistent with population-level handedness, but also
report a left directional asymmetry in Pan that may be the result of postural
and/or locomotor loading. CONCLUSION: We conclude that trabecular bone is capable
of detecting right/left directional asymmetry, but suggest coupling studies of
internal structure with analyses of other skeletal elements and cortical bone
prior to applications in the fossil record.
PMID- 27500904
TI - Microfluidic Buffer Exchange for Interference-free Micro/Nanoparticle Cell
Engineering.
AB - Engineering cells with active-ingredient-loaded micro/nanoparticles (NPs) is
becoming an increasingly popular method to enhance native therapeutic properties,
enable bio imaging and control cell phenotype. A critical yet inadequately
addressed issue is the significant number of particles that remain unbound after
cell labeling which cannot be readily removed by conventional centrifugation.
This leads to an increase in bio imaging background noise and can impart
transformative effects onto neighboring non-target cells. In this protocol, we
present an inertial microfluidics-based buffer exchange strategy termed as Dean
Flow Fractionation (DFF) to efficiently separate labeled cells from free NPs in a
high throughput manner. The developed spiral microdevice facilitates continuous
collection (>90% cell recovery) of purified cells (THP-1 and MSCs) suspended in
new buffer solution, while achieving >95% depletion of unbound fluorescent dye or
dye-loaded NPs (silica or PLGA). This single-step, size-based cell purification
strategy enables high cell processing throughput (10(6) cells/min) and is highly
useful for large-volume cell purification of micro/nanoparticle engineered cells
to achieve interference-free clinical application.
PMID- 27500903
TI - Fast Photochemical Oxidation of Proteins Maps the Topology of Intrinsic Membrane
Proteins: Light-Harvesting Complex 2 in a Nanodisc.
AB - Although membrane proteins are crucial participants in photosynthesis and other
biological processes, many lack high-resolution structures. Prior to achieving a
high-resolution structure, we are investigating whether MS-based footprinting can
provide coarse-grained protein structure by following structural changes that
occur upon ligand binding, pH change, and membrane binding. Our platform probes
topology and conformation of membrane proteins by combining MS-based
footprinting, specifically fast photochemical oxidation of proteins (FPOP), and
lipid Nanodiscs, which are more similar to the native membrane environment than
are the widely used detergent micelles. We describe here results that show a
protein's outer membrane regions are more heavily footprinted by OH radicals
whereas the regions spanning the lipid bilayer remain inert to the labeling.
Nanodiscs generally exhibit more protection of membrane proteins compared to
detergent micelles and less shielding to those protein residues that exist
outside the membrane. The combination of immobilizing the protein in Nanodiscs
and footprinting with FPOP is a feasible approach to map extra-membrane protein
surfaces, even at the amino-acid level, and to illuminate intrinsic membrane
protein topology.
PMID- 27500905
TI - Conclusions of the II International and IV Spanish Hydration Congress. Toledo,
Spain, 2nd-4th December, 2015.
AB - Water is the major component of our organism representing about 60% of total body
weight in adults and has to be obtained through the consumption of different
foods and beverages as part of our diet. Water is an essential nutrient
performing important functions, including transport of other nutrients,
elimination of waste products, temperature regulation, lubrication and structural
support. In this context, hydration through water has an essential role in health
and wellness, which has been highly acknowledged in recent years among the health
community experts such as nutritionists, dietitians, general practitioners,
pharmacists, educators, as well as by physical activity and sport sciences
experts and the general population.
PMID- 27500906
TI - Age-Related Differences of Organism-Specific Peritonitis Rates: A Single-Center
Experience.
AB - Peritonitis remains an important cause of morbidity and mortality in peritoneal
dialysis (PD) patients, but its incidence and the distribution of causative
organisms vary widely between institutions and age groups. This study was
performed to investigate the recent status and risk factors of PD-related
peritonitis and to clarify differences between age groups. We retrospectively
reviewed the medical records of 119 PD patients treated at our department between
January 2002 and January 2013. We calculated both overall and organism-specific
peritonitis rates and also analyzed risk factors. Sixty-three episodes of
peritonitis occurred during 261.5 patient-years for an incident rate of 0.24
episodes/patient-year. Multivariate analysis showed that older age (>=65 years)
and hypoalbuminemia (<3.0 g/dL) were associated with an increased risk of
peritonitis (P = 0.035 and P = 0.029, respectively). In elderly patients (>=65
years old), the rate of peritonitis due to Gram-positive and Gram-negative
bacteria was 0.17 and 0.08 episodes/patient-year, respectively, and Gram-positive
peritonitis was markedly more frequent than in younger patients (<65 years old).
In particular, there was a high frequency of Staphylococcus aureus peritonitis in
elderly patients (0.09 episodes/patient-year) and it had a poor outcome. At our
department, the risk of peritonitis was increased in older patients and patients
with hypoalbuminemia. The distribution of causative organisms was markedly
different between age groups and analysis of organism-specific peritonitis rates
helped to identify current problems with our PD program.
PMID- 27500907
TI - Accessing Three-Dimensional Crystals with Incorporated Guests through Metal
Directed Coiled-Coil Peptide Assembly.
AB - Obtaining three-dimensional (3D) protein and peptide crystals on demand requires
a precisely orchestrated hierarchical assembly of biopolymer building blocks. In
this work, we disclose a metal-ion-mediated strategy to assemble trimeric coiled
coil peptides in a head-to-tail fashion into linear strands with interstrand
interactions. This design led to hexagonal 3D peptide crystal formation within 30
min in the presence of divalent metal ions. The crystal morphology could be
controlled by varying the metal ion/peptide ratio, resulting in hexagonal discs
to rods. Diffraction studies elucidated the head-to-tail arrangement of the
coiled-coil linear strands and their hexagonal, antiparallel packing within the
crystal. Unsatisfied ligands at the hexagonal ends of the crystals were harnessed
as a powerful means to direct His-tagged fluorophores to distinct locations
within the crystals. Overall, the designed hierarchical assembly provides a
facile means to obtain 3D peptide crystals and incorporate His-tag-based cargoes
and may have potential use in drug delivery and sensor design.
PMID- 27500908
TI - The Efficacy of Internal Family Systems Therapy in the Treatment of Depression
Among Female College Students: A Pilot Study.
AB - College women are vulnerable to depression due to developmental and transitional
life changes. Early diagnosis and effective treatment is critically important.
Empirical support exists for the effectiveness of select treatment options (i.e.,
antidepressant medication, cognitive-behavioral therapy [CBT], and interpersonal
psychotherapy [IPT]), yet a significant percentage of those treated do not
benefit. In this pilot study, Internal Family Systems (IFS) therapy was tested as
an alternative approach. College women (N = 37) were randomly allocated to IFS
treatment or treatment as usual (CBT or IPT). Results demonstrated a decline in
depressive symptoms for both conditions and no significant differences in the
magnitude or rate of change. The results provide preliminary evidence for the
efficacy of IFS in the treatment of depressive symptoms.
PMID- 27500909
TI - Selection of the Rotation Direction for a Camphor Disk Resulting from Chiral
Asymmetry of a Water Chamber.
AB - Self-motion of a camphor disk rotating inside a water chamber composed of two
half-disks was investigated. The half-disks were joined along their diameter
segments, and the distance between their midpoints (ds) was considered as the
control parameter. Various types of camphor disk motions were observed depending
on ds. When ds = 0, the chamber had a circular shape, so it was symmetric. A
camphor disk showed either a clockwise (CW) or counterclockwise (CCW) rotation
with the direction determined by its initial state. The symmetry of the chamber
was broken for ds > 0. For moderate distances between the midpoints, a
unidirectional orbital motion of the disk was observed. The preferred rotation
direction was determined by the shape of the chamber, and it did not depend on
the initial rotation direction. For yet larger ds, the unidirectional circular
motion was no longer observed and the trajectory became irregular. A mathematical
model coupling the camphor disk motion with the dynamics of the developed camphor
molecular layer on water was constructed, and the numerical results were compared
with the experimental results. The selection of motion type can be explained by
considering the influence of camphor concentration on the disk trajectory through
the surface tension gradient.
PMID- 27500910
TI - Surfactant-Wrapped Multiwalled Carbon Nanotubes in Aquatic Systems: Surfactant
Displacement in the Presence of Humic Acid.
AB - Sodium dodecyl sulfate (SDS) facilitates multiwalled carbon nanotube (MWCNT)
debundling and enhances nanotube stability in the aqueous environment by
adsorbing on the nanotube surfaces, thereby increasing repulsive electrostatic
forces and steric effects. The resulting SDS-wrapped MWCNTs are utilized in
industrial applications and have been widely employed in environmental studies.
In the present study, MWCNTs adsorbed SDS during ultrasonication to form stable
MWCNTs suspensions. Desorption of SDS from MWCNTs surfaces was then investigated
as a function of Suwannee River Humic Acid (SRHA) and background electrolyte
concentrations. Due to hydrophobic effects and pi-pi interactions, MWCNTs exhibit
higher affinity for SRHA than SDS. In the presence of SRHA, SDS adsorbed on
MWCNTs was displaced. Cations (Na(+), Ca(2+)) decreased SDS desorption from
MWCNTs due to charge screening effects. Interestingly, the presence of the
divalent calcium cation facilitated multilayered SRHA adsorption on MWCNTs
through bridging effects, while monovalent sodium reduced SRHA adsorption.
Results of the present study suggest that properties of MWCNTs wrapped with
commercial surfactants will be altered when these materials are released to
surface waters and the surfactant coating will be displaced by natural organic
matter (NOM). Changes on their surfaces will significantly affect MWCNTs fate in
aquatic environments.
PMID- 27500912
TI - Structural model of amyloid fibrils for amyloidogenic peptide from Bgl2p
glucantransferase of S. cerevisiae cell wall and its modifying analog. New
morphology of amyloid fibrils.
AB - We performed a comparative study of the process of amyloid formation by short
homologous peptides with a substitution of aspartate for glutamate in position 2
VDSWNVLVAG (AspNB) and VESWNVLVAG (GluNB) - with unblocked termini. Peptide
AspNB (residues 166-175) corresponded to the predicted amyloidogenic region of
the protein glucantransferase Bgl2 from the Saccharomyces cerevisiae cell wall.
The process of amyloid formation was monitored by fluorescence spectroscopy (FS),
electron microscopy (EM), tandem mass spectrometry (TMS), and X-ray diffraction
(XD) methods. The experimental study at pH3.0 revealed formation of amyloid
fibrils with similar morphology for both peptides. Moreover, we found that the
morphology of fibrils made of untreated ammonia peptide is not mentioned in the
literature. This morphology resembles snakes lying side by side in the form of a
wave without intertwining. Irrespective of the way of the peptide preparation,
the rate of fibril formation is higher for AspNB than for GluNB. However,
preliminary treatment with ammonia highly affected fibril morphology especially
for AspNB. Such treatment allowed us to obtain a lag period during the process of
amyloid formation. It showed that the process was nucleation-dependent. With or
without treatment, amyloid fibrils consisted of ring-like oligomers with the
diameter of about 6nm packed either directly ring-to-ring or ring-on-ring with a
slight shift. We also proposed the molecular structure of amyloid fibrils for two
studied peptides.
PMID- 27500913
TI - Does Reducing Basal Insulin During Ramadan Fasting by Children and Adolescents
with Type 1 Diabetes Decrease the Risk of Symptomatic Hypoglycemia?
AB - BACKGROUND: Ramadan fasting by patients with type 1 diabetes might predispose
them to hypoglycemia. There are no data on the optimal way of adjusting basal
insulin during fasting. We aim at studying whether reducing basal insulin during
Ramadan reduces the frequency of symptomatic hypoglycemia. METHODS: We enrolled
children and adolescents with type 1 diabetes who intended to fast during
Ramadan. Logbooks were given to subjects to mark days fasted, symptomatic
hypoglycemia, and dose of basal insulin on all days of Ramadan. Logbooks were
examined. Glucometers and insulin pumps were downloaded. RESULTS: Seventy-five
patients were enrolled. The age was 10.2-18.9 (14.5) years. Sixty-eight patients
had results analyzed. Forty-one patients were on pumps, and 27 patients were on
multiple daily injections (MDI). Mean HbA1c was 7.9 (1.2) and 8.4 (1.3) for the
pump and the MDI, respectively (P = 0.007). Thirty-nine patients had hypoglycemia
leading to breaking fast. The mean number of episodes of breaking fast was 3 (1
8). Thirty-five of the 68 patients had reduced basal insulin. The difference in
the frequency of hypoglycemia in those who reduced/did not reduce insulin was not
statistically significant (P > 0.10). Fifteen patients on MDI and 24 patients on
pumps had at least one episode of breaking fast. Six and 18 of the patients on
MDI and pumps, respectively, reduced basal insulin (P > 0.10). CONCLUSION: This
is the first study examining the impact of reduction of basal insulin on
hypoglycemia in adolescents. Reducing basal insulin during Ramadan fasting does
not decrease the risk of symptomatic hypoglycemia. Use of the insulin pump does
not appear to be different from MDI in the frequency of occurrence of
hypoglycemia.
PMID- 27500911
TI - Advances and challenges: dendritic cell vaccination strategies for glioblastoma.
AB - INTRODUCTION: Glioblastoma is the most common primary brain tumor in adults and
prognosis remains poor with a median survival of approximately 15-17 months. This
review provides an overview of recent advances in the field of glioblastoma
immunotherapy. Areas covered: Recent advances in dendritic cell vaccination
immunotherapy are showing encouraging results in clinical trials and promise to
extend patient survival. In this report we discuss current scientific knowledge
regarding dendritic cell (DC) vaccines, including approaches to differentiating,
priming, and injecting dendritic cells to achieve maximal anti-tumor efficacy in
glioblastoma. These findings are compared to recently completed and currently
ongoing glioblastoma clinical trials. Novel methods such as 'fastDCs' and
vaccines targeting DCs in-vivo may offer more effective treatment when compared
to traditional DC vaccines and have already entered the clinic. Expert
commentary: Finally, we discuss the challenges of T-cell dysfunctions caused by
glioblastoma immunosuppression and how they affect dendritic cell vaccinations
approaches.
PMID- 27500914
TI - Optimal prevention of transfusion-transmitted cytomegalovirus (TTCMV) infection
by modern leukocyte reduction alone: CMV sero/antibody-negative donors needed
only for leukocyte products.
PMID- 27500915
TI - Enhancing blood safety in Africa: stepping forward.
PMID- 27500916
TI - Dissecting the metabolic pathways controlling platelet survival in vivo: are our
platelets what they eat?
PMID- 27500917
TI - When visual inspection of the palpebral conjunctivae falls short ....
PMID- 27500918
TI - Cancer-related microangiopathic hemolytic anemia.
PMID- 27500920
TI - Mortality rates in major and subthreshold depression: 10-year follow-up of a
Singaporean population cohort of older adults.
AB - OBJECTIVES: To investigate the associations of major and subthreshold depression
with all-cause, cardiovascular disease and stroke mortality, and the extent to
which health behaviour, medical comorbidity and functional disability explained
the associations. METHODS: A cohort of 1070 persons aged >=60 with Geriatric
Mental State (GMS) diagnoses of major and subthreshold depression, and data on
health behaviour (smoking, alcohol, physical activity) and physical comorbidity
(hypertension, diabetes, cardiovascular disease, stroke, chronic pulmonary
disease, multi-comorbidity and activity of daily living disability) at baseline
(15 Feb 2003 - 30 Mar 2004) were followed up on mortality from 1 Jan 2005 to 31
Dec 2012. RESULTS: Major and subthreshold depression was present in 5.1% and 9.9%
of the participants at baseline. The all-cause mortality HR adjusted for age,
sex, ethnicity and marital status was 1.73 (95% CI, 1.11-2.67) for major
depression and 1.38 (95% CI, 0.96-1.97) for subthreshold depression. In
hierarchical models, the addition of health behaviour and especially physical
comorbidity substantially reduced the HR estimates for all-cause mortality
associated with major depression (HR=1.39, 95% CI, 0.89-2.18) and subthreshold
depression (HR=0.94, 95% CI, 0.64-1.37). Controlling for the effects of all
variables, only major depression was significantly associated with increased
cardiovascular disease and stroke mortality (HR=2.10, 95% CI, 1.07-4.11).
CONCLUSIONS: Both major and subthreshold depression were associated with
increased mortality, largely due to hazardous behaviours and physical
comorbidity. Only major depression per se was independently associated with
excess cardiovascular disease and stroke mortality.
PMID- 27500921
TI - Correction: A challenge for theranostics: is the optimal particle for therapy
also optimal for diagnostics?
AB - Correction for 'A challenge for theranostics: is the optimal particle for therapy
also optimal for diagnostics?' by Tamar Dreifuss, et al., Nanoscale, 2015, 7,
15175-15184.
PMID- 27500922
TI - A Method to Quantify Visual Information Processing in Children Using Eye
Tracking.
AB - Visual problems that occur early in life can have major impact on a child's
development. Without verbal communication and only based on observational
methods, it is difficult to make a quantitative assessment of a child's visual
problems. This limits accurate diagnostics in children under the age of 4 years
and in children with intellectual disabilities. Here we describe a quantitative
method that overcomes these problems. The method uses a remote eye tracker and a
four choice preferential looking paradigm to measure eye movement responses to
different visual stimuli. The child sits without head support in front of a
monitor with integrated infrared cameras. In one of four monitor quadrants a
visual stimulus is presented. Each stimulus has a specific visual modality with
respect to the background, e.g., form, motion, contrast or color. From the
reflexive eye movement responses to these specific visual modalities, output
parameters such as reaction times, fixation accuracy and fixation duration are
calculated to quantify a child's viewing behavior. With this approach, the
quality of visual information processing can be assessed without the use of
communication. By comparing results with reference values obtained in typically
developing children from 0-12 years, the method provides a characterization of
visual information processing in visually impaired children. The quantitative
information provided by this method can be advantageous for the field of clinical
visual assessment and rehabilitation in multiple ways. The parameter values
provide a good basis to: (i) characterize early visual capacities and
consequently to enable early interventions; (ii) compare risk groups and follow
visual development over time; and (iii), construct an individual visual profile
for each child.
PMID- 27500923
TI - Improved Heterojunction Quality in Cu2O-based Solar Cells Through the
Optimization of Atmospheric Pressure Spatial Atomic Layer Deposited Zn1-xMgxO.
AB - Atmospheric pressure spatial atomic layer deposition (AP-SALD) was used to
deposit n-type ZnO and Zn1-xMgxO thin films onto p-type thermally oxidized Cu2O
substrates outside vacuum at low temperature. The performance of photovoltaic
devices featuring atmospherically fabricated ZnO/Cu2O heterojunction was
dependent on the conditions of AP-SALD film deposition, namely, the substrate
temperature and deposition time, as well as on the Cu2O substrate exposure to
oxidizing agents prior to and during the ZnO deposition. Superficial Cu2O to CuO
oxidation was identified as a limiting factor to heterojunction quality due to
recombination at the ZnO/Cu2O interface. Optimization of AP-SALD conditions as
well as keeping Cu2O away from air and moisture in order to minimize Cu2O surface
oxidation led to improved device performance. A three-fold increase in the open
circuit voltage (up to 0.65 V) and a two-fold increase in the short-circuit
current density produced solar cells with a record 2.2% power conversion
efficiency (PCE). This PCE is the highest reported for a Zn1-xMgxO/Cu2O
heterojunction formed outside vacuum, which highlights atmospheric pressure
spatial ALD as a promising technique for inexpensive and scalable fabrication of
Cu2O-based photovoltaics.
PMID- 27500924
TI - Laboratory Simulation of an Iron(II)-rich Precambrian Marine Upwelling System to
Explore the Growth of Photosynthetic Bacteria.
AB - A conventional concept for the deposition of some Precambrian Banded Iron
Formations (BIF) proceeds on the assumption that ferrous iron [Fe(II)] upwelling
from hydrothermal sources in the Precambrian ocean was oxidized by molecular
oxygen [O2] produced by cyanobacteria. The oldest BIFs, deposited prior to the
Great Oxidation Event (GOE) at about 2.4 billion years (Gy) ago, could have
formed by direct oxidation of Fe(II) by anoxygenic photoferrotrophs under anoxic
conditions. As a method for testing the geochemical and mineralogical patterns
that develop under different biological scenarios, we designed a 40 cm long
vertical flow-through column to simulate an anoxic Fe(II)-rich marine upwelling
system representative of an ancient ocean on a lab scale. The cylinder was packed
with a porous glass bead matrix to stabilize the geochemical gradients, and
liquid samples for iron quantification could be taken throughout the water
column. Dissolved oxygen was detected non-invasively via optodes from the
outside. Results from biotic experiments that involved upwelling fluxes of Fe(II)
from the bottom, a distinct light gradient from top, and cyanobacteria present in
the water column, show clear evidence for the formation of Fe(III) mineral
precipitates and development of a chemocline between Fe(II) and O2. This column
allows us to test hypotheses for the formation of the BIFs by culturing
cyanobacteria (and in the future photoferrotrophs) under simulated marine
Precambrian conditions. Furthermore we hypothesize that our column concept allows
for the simulation of various chemical and physical environments - including
shallow marine or lacustrine sediments.
PMID- 27500925
TI - Dieter C. Gruenert, PhD (1949-2016).
PMID- 27500926
TI - Efficacy of Tumor-Targeting Salmonella A1-R on a Melanoma Patient-Derived
Orthotopic Xenograft (PDOX) Nude-Mouse Model.
AB - Tumor-targeting Salmonella enterica serovar Typhimurium A1-R (Salmonella A1-R)
had strong efficacy on a melanoma patient-derived orthotopic xenograft (PDOX)
nude-mouse model. GFP-expressing Salmonella A1-R highly and selectively colonized
the PDOX melanoma and significantly suppressed tumor growth (p = 0.021). The
combination of Salmonella A1-R and cisplatinum (CDDP), both at low-dose, also
significantly suppressed the growth of the melanoma PDOX (P = 0.001). Salmonella
A1-R has future clinical potential for combination chemotherapy with CDDP of
melanoma, a highly-recalcitrant cancer.
PMID- 27500927
TI - Management of acute viral bronchiolitis in children: Evidence beyond guidelines.
AB - Acute viral bronchiolitis is one of the leading causes of worldwide admission of
children under 2 years of age during winter months. There is a lack of consensus
regarding the clinical definition of acute viral bronchiolitis in children and
hence the management varies across the globe. The purpose of this article is to
review the epidemiology, etiology, risk factors, pathophysiology, clinical
presentation, assessment and management of children with respiratory syncytial
virus (RSV) bronchiolitis. The available evidence in the worldwide literature
suggests that supportive and symptomatic management is still the mainstay of
management in this condition. The key to reducing the morbidity and mortality in
children with RSV bronchiolitis is through prevention of infection through
immunoprophylaxis especially in high-risk children.
PMID- 27500928
TI - Femur Window Chamber Model for In Vivo Cell Tracking in the Murine Bone Marrow.
AB - Bone marrow is a complex organ that contains various hematopoietic and non
hematopoietic cells. These cells are involved in many biological processes,
including hematopoiesis, immune regulation and tumor regulation. Commonly used
methods for understanding cellular actions in the bone marrow, such as histology
and blood counts, provide static information rather than capturing the dynamic
action of multiple cellular components in vivo. To complement the standard
methods, a window chamber (WC)-based model was developed to enable serial in vivo
imaging of cells and structures in the murine bone marrow. This protocol
describes a surgical procedure for installing the WC in the femur, in order to
facilitate long-term optical access to the femoral bone marrow. In particular, to
demonstrate its experimental utility, this WC approach was used to image and
track neutrophils within the vascular network of the femur, thereby providing a
novel method to visualize and quantify immune cell trafficking and regulation in
the bone marrow. This method can be applied to study various biological processes
in the murine bone marrow, such as hematopoiesis, stem cell transplantation, and
immune responses in pathological conditions, including cancer.
PMID- 27500929
TI - In Vivo Cannulation Methods for Cardiomyocytes Isolation from Heart Disease
Models.
AB - Isolation of high quality cardiomyocytes is critically important for achieving
successful experiments in many cellular and molecular cardiology studies. Methods
for isolating cardiomyocytes from the murine heart generally are time-sensitive
and experience-dependent, and often fail to produce high quality cells. Major
technical difficulties can be related to the surgical procedures needed to
explant the heart and to cannulate the vessel to mount onto the Langendorff
system before in vitro reperfusion can begin. During this period, transient
hypoxia and ischemia may damage the heart, resulting in low yield and poor
quality of cells, especially for heart disease models that have fragile cells. We
have developed novel in vivo cannulation methods to minimize hypoxia and
ischemia, and fine-tuned the entire protocol to produce high quality ventricular
myocytes. The high cell quality has been confirmed using important structural and
functional criteria such as morphology, t-tubule structure, action potential
morphology, Ca2+ signaling, responsiveness to beta-adrenergic agonist, and
ability to have robust contraction under mechanically loaded condition. Together
these assessments show the preservation of the cardiac excitation-contraction
machinery in cells isolated using this technique. The in vivo cannulation method
enables consistent isolation of high-quality cardiomyocytes, even from heart
disease models that were notoriously difficult for cell isolation using
traditional methods.
PMID- 27500930
TI - Spectral Cytometry Has Unique Properties Allowing Multicolor Analysis of Cell
Suspensions Isolated from Solid Tissues.
AB - Flow cytometry, initially developed to analyze surface protein expression in
hematopoietic cells, has increased in analytical complexity and is now widely
used to identify cells from different tissues and organisms. As a consequence,
data analysis became increasingly difficult due the need of large multi
parametric compensation matrices and to the eventual auto-fluorescence frequently
found in cell suspensions obtained from solid organs. In contrast with
conventional flow cytometry that detects the emission peak of fluorochromes,
spectral flow cytometry distinguishes the shapes of emission spectra along a
large range of continuous wave lengths. The data is analyzed with an algorithm
that replaces compensation matrices and treats auto-fluorescence as an
independent parameter. Thus, spectral flow cytometry should be capable to
discriminate fluorochromes with similar emission peaks and provide multi
parametric analysis without compensation requirements. Here we show that spectral
flow cytometry achieves a 21-parametric (19 fluorescent probes) characterization
and deals with auto-fluorescent cells, providing high resolution of specifically
fluorescence-labeled populations. Our results showed that spectral flow cytometry
has advantages in the analysis of cell populations of tissues difficult to
characterize in conventional flow cytometry, such as heart and intestine.
Spectral flow cytometry thus combines the multi-parametric analytical capacity of
the highest performing conventional flow cytometry without the requirement for
compensation and enabling auto-fluorescence management.
PMID- 27500931
TI - Evolution of diagnosis and clinical outcomes in acute aortic dissection: data
from the International Registry of Acute Aortic Dissection.
PMID- 27500932
TI - Racial/Ethnic Disparities in Measures of Self-reported Psychosocial States and
Traits during Pregnancy.
AB - Background The aim of this study was to determine whether racial/ethnic
differences in psychosocial measures, independent of economic status, exist among
a large population of pregnant nulliparas. Methods Between October 2010 and
September 2013, nulliparous women at eight U.S. medical centers were followed
longitudinally during pregnancy and completed validated instruments to quantify
several psychosocial domains: Cohen Perceived Stress Scale, trait subscale of the
Spielberger Anxiety Inventory, Connor-Davidson Resilience Scale, Multidimensional
Scale of Perceived Social Support, Krieger Racism Scale, Edinburgh Postnatal
Depression Scale, and the Pregnancy Experience Scale. Scores were stratified and
compared by self-reported race, ethnicity, and income. Results Complete data were
available for 8,128 of the 10,038 women enrolled in the study. For all measures,
race and ethnicity were significantly associated (p < 0.001) with survey scores.
Non-Hispanic black (NHB) women were most likely to score in the most unfavorable
category for all measures, with the exception of the Pregnancy Experience Scale.
The magnitude of these differences did not differ by income status (interaction,
p > 0.05) except on the Krieger racism survey and the Edinburgh depression
survey, which were exacerbated among NHB women with higher income (interaction, p
< 0.001). Conclusion Significant racial/ethnic disparities, independent of income
status, exist in psychosocial measures during pregnancy.
PMID- 27500933
TI - Comparison of Respiratory Outcomes between Preterm Small-For-Gestational-Age and
Appropriate-For-Gestational-Age Infants.
AB - Objective This study aims to determine whether preterm infants who are small for
gestational age (SGA) are more likely to have respiratory distress syndrome (RDS)
compared with appropriate-for-gestational-age infants. Methods Secondary analysis
of a multicenter trial evaluating magnesium for neuroprotection. Nonanomalous,
singleton gestations delivered between 22 0/7 and 36 6/7 weeks were included.
Large-for-gestational-age infants were excluded. We performed a nested case
control study. Cases were infants with RDS; controls were infants without RDS.
The sample size estimates revealed 779 subjects/group were needed to achieve a
80% power to demonstrate a 1/3 difference in RDS. We fit a multivariable logistic
regression model to adjust for confounders. We assessed the association of SGA
with RDS and a composite adverse respiratory and neonatal outcome. Results
Overall, 947 cases and 920 controls were included. The groups differed by
gestational age at delivery, antibiotic exposure, mode of delivery, infant
gender, and birth weight. SGA was not associated with RDS (adjusted odds ratio
[aOR]: 1.07, 95% confidence interval [CI]: 0.48-2.38) or the composite
respiratory (aOR: 0.87, 95% CI: 0.37-2.04) or adverse neonatal outcome (aOR:
0.65, 95% CI: 0.27-1.54). RDS and the composite respiratory outcome were most
associated with earlier gestational age at delivery, cesarean delivery, and male
gender. Conclusion SGA is not associated with RDS or other adverse respiratory
and neonatal composites.
PMID- 27500934
TI - Beta Diversity in a Highly Heterogeneous Area: Disentangling Species and
Taxonomic Dissimilarity for Terrestrial Vertebrates.
AB - Quantifying differences in species composition among communities provides
important information related to the distribution, conservation and management of
biodiversity, especially when two components are recognized: dissimilarity due to
turnover, and dissimilarity due to richness differences. The ecoregions in
central Mexico, within the Mexican Transition Zone, have outstanding
environmental heterogeneity and harbor huge biological richness, besides
differences in the origin of the biota. Therefore, biodiversity studies in this
area require the use of complementary measures to achieve appropriate information
that may help in the design of conservation strategies. In this work we analyze
the dissimilarity of terrestrial vertebrates, and the components of turnover and
richness differences, among six ecoregions in the state of Hidalgo, central
Mexico. We follow two approaches: one based on species level dissimilarity, and
the second on taxonomic dissimilarity. We used databases from the project
"Biodiversity in the state of Hidalgo". Our results indicate that species
dissimilarity is higher than taxonomic dissimilarity, and that turnover
contributes more than richness differences, both for species and taxonomic total
dissimilarity. Moreover, total dissimilarity, turnover dissimilarity and the
dissimilarity due to richness differences were positively related in the four
vertebrate groups. Reptiles had the highest values of dissimilarity, followed by
mammals, amphibians and birds. For reptiles, birds, and mammals, species turnover
was the most important component, while richness differences had a higher
contribution for amphibians. The highest values of dissimilarity occurred between
environmentally contrasting ecoregions (i.e., tropical and temperate forests),
which suggests that environmental heterogeneity and differences in the origin of
biotas are key factors driving beta diversity of terrestrial vertebrates among
ecoregions in this complex area.
PMID- 27500935
TI - Disturbance in the Mucosa-Associated Commensal Bacteria Is Associated with the
Exacerbation of Chronic Colitis by Repeated Psychological Stress; Is That the New
Target of Probiotics?
AB - Psychological stress can exacerbate inflammatory bowel disease. However, the
mechanisms underlying how psychological stress affects gut inflammation remain
unclear. Here, we focused on the relationship between changes in the microbial
community of mucosa-associated commensal bacteria (MACB) and mucosal immune
responses induced by chronic psychological stress in a murine model of ulcerative
colitis. Furthermore, we examined the effect of probiotic treatment on
exacerbated colitis and MACB composition changes induced by chronic psychological
stress. Repeated water avoidance stress (rWAS) in B6-Tcra-/- mice severely
exacerbated colitis, which was evaluated by both colorectal tissue weight and
histological score of colitis. rWAS treatment increased mRNA expression of UCN2
and IFN-gamma in large intestinal lamina propria mononuclear cells (LI-LPMC).
Interestingly, exacerbated colitis was associated with changes in the microbial
community of MACB, specifically loss of bacterial species diversity and an
increase in the component ratio of Clostridium, revealed by 16S rRNA gene
amplicon analysis. Finally, the oral administration of a probiotic Lactobacillus
strain was protective against the exacerbation of colitis and was associated with
a change in the bacterial community of MACB in rWAS-exposed Tcra-/- mice. Taken
together, these results suggested that loss of species diversity in MACB might
play a key role in exacerbated colitis induced by chronic psychological stress.
In addition, probiotic treatment may be used as a tool to preserve the diversity
of bacterial species in MACB and alleviate gut inflammation induced by
psychological stress.
PMID- 27500940
TI - Application of a Dual-Hybrid Direct Random Phase Approximation to Water Clusters.
AB - In water clusters, there is a delicate balance of van der Waals interactions and
hydrogen bonds. Although semilocal and nonlocal density functional approximations
have been recently routinely applied to water in various phases, the accurate
description of hydrogen bonds remains a challenge. The most popular density
functional approaches fail to predict the correct ordering of the energies of
water clusters. To illustrate the required accuracy, the CCSD(T) complete basis
set extrapolated dissociation energy difference between the two lowest energy
hexamer structures is 0.06 kcal mol(-1) per monomer. In this work, we assessed
interaction energies in neutral and ionic water clusters with various density
functionals with or without van der Waals correction. Generally, van der Waals
approximations play a significant role in clusters with increasing size, while
hybrid functionals improve the description of hydrogen bonds. Despite these
general trends, none of the tested density functional approximations with or
without van der Waals correction and exact exchange mixing can lead to a uniform
performance for neutral and ionic water clusters. The recently constructed dual
hybrid dRPA75 approximation is a successful combination of exact and semilocal
exchange, and nonlocal correlation in its energy, while utilizing a high fraction
of exact exchange. We have shown that the dRPA75 method has a systematic error,
which can be efficiently compensated for by the aug-cc-pVTZ basis set for small-
and medium-sized water clusters.
PMID- 27500936
TI - Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA
Polymerase I.
AB - Ribosome biogenesis is essential for cell growth and proliferation and is
commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor
signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt
signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show
that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and
generates a chromatin state with reduced transcription of rDNA by RNA polymerase
I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1),
which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions
of the chromosome. Upon DVL1 binding, the Pol I transcription activator and
deacetylase Sirtuin 7 (SIRT7) releases from rDNA loci, concomitant with
disassembly of Pol I transcription machinery at the rDNA promoter. These findings
reveal that Wnt5a signals through DVL1 to suppress rRNA transcription. This
provides a novel mechanism for how Wnt5a exerts tumor suppressive effects and why
disruption of Wnt5a signaling enhances mammary tumor growth in vivo.
PMID- 27500941
TI - Palladium-Catalyzed Oxidative Sulfenylation of Indoles and Related Electron-Rich
Heteroarenes with Aryl Boronic Acids and Elemental Sulfur.
AB - An efficient and convenient palladium-catalyzed C-H bond oxidative sulfenylation
of indoles and related electron-rich heteroarenes with aryl boronic acids and
elemental sulfur has been described. This procedure provides a useful and direct
approach for the assembly of a wide range of structurally diverse 3
sulfenylheteroarenes with moderate to excellent yields from simple and readily
available starting materials. Moreover, this synthetic protocol is suitable for N
protected and unprotected indoles. Notably, the construction of two C-S bonds in
one step was also achieved in this transformation.
PMID- 27500942
TI - Gender and genetic contributions to weight identity among adolescents and young
adults in the U.S.
AB - In this paper, we investigate the possibility that genetic variation contributes
to self-perceived weight status among adolescents and young adults in the U.S.
Using samples of identical and fraternal twins across four waves of the National
Longitudinal Study of Adolescent to Adult Health (Add Health) study, we calculate
heritability estimates for objective body mass index (BMI) that are in line with
previous estimates. We also show that perceived weight status is heritable (h(2)
~ 0.47) and most importantly that this trait continues to be heritable above and
beyond objective BMI (h(2) ~ 0.25). We then demonstrate significant sex
differences in the heritability of weight identity across the four waves of the
study, where h(2)women = 0.39, 0.35, 0.40, and 0.50 for each wave, respectively,
and h(2)men = 0.10, 0.10, 0.23, and 0.03. These results call for a deeper
consideration of both identity and gender in genetics research.
PMID- 27500943
TI - Do early life cognitive ability and self-regulation skills explain socio-economic
inequalities in academic achievement? An effect decomposition analysis in UK and
Australian cohorts.
AB - Socio-economic inequalities in academic achievement emerge early in life and are
observed across the globe. Cognitive ability and "non-cognitive" attributes (such
as self-regulation) are the focus of many early years' interventions. Despite
this, little research has compared the contributions of early cognitive and self
regulation abilities as separate pathways to inequalities in academic
achievement. We examined this in two nationally representative cohorts in the UK
(Millennium Cohort Study, n = 11,168; 61% original cohort) and Australia (LSAC, n
= 3028; 59% original cohort). An effect decomposition method was used to examine
the pathways from socio-economic disadvantage (in infancy) to two academic
outcomes: 'low' maths and literacy scores (based on bottom quintile) at age 7-9
years. Risk ratios (RRs, and bootstrap 95% confidence intervals) were estimated
with binary regression for each pathway of interest: the 'direct effect' of socio
economic disadvantage on academic achievement (not acting through self-regulation
and cognitive ability in early childhood), and the 'indirect effects' of socio
economic disadvantage acting via self-regulation and cognitive ability
(separately). Analyses were adjusted for baseline and intermediate confounding.
Children from less advantaged families were up to twice as likely to be in the
lowest quintile of maths and literacy scores. Around two-thirds of this elevated
risk was 'direct' and the majority of the remainder was mediated by early
cognitive ability and not self-regulation. For example in LSAC: the RR for the
direct pathway from socio-economic disadvantage to poor maths scores was 1.46
(95% CI: 1.17-1.79). The indirect effect of socio-economic disadvantage through
cognitive ability (RR = 1.13 [1.06-1.22]) was larger than the indirect effect
through self-regulation (1.05 [1.01-1.11]). Similar patterns were observed for
both outcomes and in both cohorts. Policies to alleviate social inequality (e.g.
child poverty reduction) remain important for closing the academic achievement
gap. Early interventions to improve cognitive ability (rather than self
regulation) also hold potential for reducing inequalities in children's academic
outcomes.
PMID- 27500944
TI - Development of Solution-Processed ZnO Nanorod Arrays Based Photodetectors and the
Improvement of UV Photoresponse via AZO Seed Layers.
AB - Designing a rational structure and developing an efficient fabrication technique
for bottom-up devices offer a promising opportunity for achieving high
performance devices. In this work, we studied how Al-doped ZnO (AZO) seed layer
films influence the morphology and optical and electrical properties for ZnO
aligned nanorod arrays (NRs) and then the performance of ZnO NRs based
ultraviolet photodetectors (UV PDs) with Au/ZnO NRs Schottky junctions and p
CuSCN/n-ZnO NRs heterojunctions. The PD with AZO thin film with 0.5 at. % Al
doping (named as AZO (0.5%)) exhibited more excellent photoresponse properties
than that with pristine ZnO and AZO (1%) thin films. This phenomenon can be
ascribed to the good light transmission of the AZO layer, increased density of
the NRs, and improved crystallinity of ZnO NRs. The PDs based on CuSCN/ZnO NRs
heterojunctions showed good rectification characteristics in the dark and self
powered UV photoresponse properties with excellent stability and reproducibility
under low-intensity illumination conditions. A large responsivity located at 365
nm of 22.5 mA/W was achieved for the PD with AZO (0.5%) thin film without applied
bias. The internal electric field originated from p-CuSCN/n-ZnO NRs
heterojunctions can separate photogenerated carriers in ZnO NRs and drift toward
the corresponding electrode.
PMID- 27500945
TI - Modeling zero-modified count and semicontinuous data in health services research
Part 1: background and overview.
AB - Health services data often contain a high proportion of zeros. In studies
examining patient hospitalization rates, for instance, many patients will have no
hospitalizations, resulting in a count of zero. When the number of zeros is
greater or less than expected under a standard count model, the data are said to
be zero modified relative to the standard model. A similar phenomenon arises with
semicontinuous data, which are characterized by a spike at zero followed by a
continuous distribution with positive support. When analyzing zero-modified count
and semicontinuous data, flexible mixture distributions are often needed to
accommodate both the excess zeros and the typically skewed distribution of
nonzero values. Various models have been introduced over the past three decades
to accommodate such data, including hurdle models, zero-inflated models, and two
part semicontinuous models. This tutorial describes recent modeling strategies
for zero-modified count and semicontinuous data and highlights their role in
health services research studies. Part 1 of the tutorial, presented here,
provides a general overview of the topic. Part 2, appearing as a companion piece
in this issue of Statistics in Medicine, discusses three case studies
illustrating applications of the methods to health services research. Copyright
(c) 2016 John Wiley & Sons, Ltd.
PMID- 27500946
TI - Neon-Bearing Ammonium Metal Formates: Formation and Behaviour under Pressure.
AB - The incorporation of noble gas atoms, in particular neon, into the pores of
network structures is very challenging due to the weak interactions they
experience with the network solid. Using high-pressure single-crystal X-ray
diffraction, we demonstrate that neon atoms enter into the extended network of
ammonium metal formates, thus forming compounds Nex [NH4 ][M(HCOO)3 ]. This
phenomenon modifies the compressional and structural behaviours of the ammonium
metal formates under pressure. The neon atoms can be clearly localised within the
centre of [M(HCOO)3 ]5 cages and the total saturation of this site is achieved
after ~1.5 GPa. We find that by using argon as the pressure-transmitting medium,
the inclusion inside [NH4 ][M(HCOO)3 ] is inhibited due to the larger size of the
argon. This study illustrates the size selectivity of [NH4 ][M(HCOO)3 ] compounds
between neon and argon insertion under pressure, and the effect of inclusion on
the high-pressure behaviour of neon-bearing ammonium metal formates.
PMID- 27500948
TI - Dual-Template Synthesis of 2D Mesoporous Polypyrrole Nanosheets with Controlled
Pore Size.
AB - The first synergistic dual-template self-assembly approach is presented for
bottom-up construction of 2D mesoporous polypyrrole nanosheets based on different
supramolecular assemblies, which feature a double-layered architecture,
controlled pore sizes, ultrathin thickness, and large surface area. The unique
structure rends them with superior reversible discharge capability, rate
performance, and stable cyclability when serving as the cathode materials for Na
ion batteries.
PMID- 27500947
TI - Plant peroxisomes: recent discoveries in functional complexity, organelle
homeostasis, and morphological dynamics.
AB - Peroxisomes are essential for life in plants. These organelles house a variety of
metabolic processes that generate and inactivate reactive oxygen species. Our
knowledge of pathways and mechanisms that depend on peroxisomes and their
constituent enzymes continues to grow, and in this review we highlight recent
advances in understanding the identity and biological functions of peroxisomal
enzymes and metabolic processes. We also review how peroxisomal matrix and
membrane proteins enter the organelle from their sites of synthesis. Peroxisome
homeostasis is regulated by specific degradation mechanisms, and we discuss the
contributions of specialized autophagy and a peroxisomal protease to the
degradation of entire peroxisomes and peroxisomal enzymes that are damaged or
superfluous. Finally, we review how peroxisomes can flexibly change their
morphology to facilitate inter-organellar contacts.
PMID- 27500949
TI - Phase 3, open-label, randomized study of the pharmacokinetics, efficacy and
safety of ixekizumab following subcutaneous administration using a prefilled
syringe or an autoinjector in patients with moderate-to-severe plaque psoriasis
(UNCOVER-A).
AB - BACKGROUND: The efficacy of ixekizumab, an anti-interleukin-17A (anti-IL-17A)
monoclonal IgG4 antibody, was demonstrated in moderate-to-severe psoriasis
patients when administered via prefilled syringe (PFS). OBJECTIVE: To evaluate
the effect of two drug delivery devices on the pharmacokinetics (PK) of
ixekizumab as well as efficacy and safety with both devices. METHODS: In the
first 12 weeks of an open-label, phase 3 study, moderate-to-severe psoriasis
patients were randomized to ixekizumab delivery via PFS or autoinjector device.
Randomization was stratified by weight (<80 kg, 80-100 kg, >100 kg), injection
assistance (yes/no) and injection site (arm, thigh or abdomen). Following a 160
mg initial dose at week 0, patients received subcutaneous 80-mg ixekizumab as a
single injection every 2 weeks for 12 weeks. Blood samples were collected
following the initial 160-mg dose on days 2, 4, 7, 10 and 14 for PK analysis.
Primary PK parameters were maximum concentration (Cmax ) and area under the curve
(AUC0-tlast ) where tlast is the time of last sample (14 days +/- 24 h). Efficacy
was assessed by percent improvement on the Psoriasis Area and Severity Index
(PASI) at week 12. Adverse event reporting, vital signs and clinical laboratory
data were used to evaluate safety. RESULTS: Of 204 randomized patients, 192 were
included in the PK analysis (PFS: 94; autoinjector: 98). The PFS and autoinjector
showed similar geometric mean Cmax (90% CI) [15.0 MUg/mL (13.9-16.1) vs. 14.8
MUg/mL (13.8-15.9)] and geometric mean AUC0-tlast (90% CI) [157 MUg * day/mL (147
168) vs. 154 MUg * day/mL (144-165)]. When comparing Cmax and AUC0-tlast of the
autoinjector to PFS, the geometric LS mean ratios were 0.97. At week 12, mean
percent PASI improvement (via modified baseline observation carried forward) was
similar with the PFS (89.3%) and autoinjector (86.9%). Both devices had safety
results that were consistent with the known safety profile of ixekizumab.
CONCLUSION: The PK, efficacy and safety of ixekizumab administered subcutaneously
by PFS and autoinjector were similar. Clinicaltrials.gov number: NCT01777191
https://clinicaltrials.gov/ct2/show/NCT01777191.
PMID- 27500950
TI - Sixty as the new forty: considerations on older related stem cell donors.
AB - The era of reduced-intensity allogeneic stem cell transplantation, with its
emphasis on older patients, has created new challenges in the management of what
is now an older related stem cell donor population. These donors are now on
average no less than 10 years older than in the mid-1990s. Donors over 70 years
of age are no longer isolated or exceptional cases. They may still be considered
eligible for donation but many of them, based on the older age and their medical
history, may no longer fully qualify as 'healthy' or 'normal'. The older the
donor, the more likely that hematologic abnormalities, comorbidities and treated
malignancies will complicate the picture. Assessing the risk-benefit ratio for
both donor and recipient can now be more challenging than ever.
PMID- 27500951
TI - Left ventricular vascular and metabolic adaptations to high-intensity interval
and moderate intensity continuous training: a randomized trial in healthy middle
aged men.
AB - KEY POINTS: High-intensity interval training (HIIT) has become popular, time
sparing alternative to moderate intensity continuous training (MICT), although
the cardiac vascular and metabolic effects of HIIT are incompletely known. We
compared the effects of 2-week interventions with HIIT and MICT on myocardial
perfusion and free fatty acid and glucose uptake. Insulin-stimulated myocardial
glucose uptake was decreased by training without any significantly different
response between the groups, whereas free fatty acid uptake remained unchanged.
Adenosine-stimulated myocardial perfusion responded differently to the training
modes (change in mean HIIT: -19%; MICT: +9%; P = 0.03 for interaction) and was
correlated with myocardial glucose uptake for the entire dataset and especially
after HIIT training. HIIT and MICT induce similar metabolic and functional
changes in the heart, although myocardial vascular hyperaemic reactivity is
impaired after HIIT, and this should be considered when prescribing very intense
HIIT for previously untrained subjects. ABSTRACT: High-intensity interval
training (HIIT) is a time-efficient way of obtaining the health benefits of
exercise, although the cardiac effects of this training mode are incompletely
known. We compared the effects of short-term HIIT and moderate intensity
continuous training (MICT) interventions on myocardial perfusion and metabolism
and cardiac function in healthy, sedentary, middle-aged men. Twenty-eight
healthy, middle-aged men were randomized to either HIIT or MICT groups (n = 14 in
both) and underwent six cycle ergometer training sessions within 2 weeks (HIIT
session: 4-6 * 30 s all-out cycling/4 min recovery, MICT session 40-60 min at 60%
VO2 peak ). Cardiac magnetic resonance imaging (CMRI) was performed to measure
cardiac structure and function and positron emission tomography was used to
measure myocardial perfusion at baseline and during adenosine stimulation,
insulin-stimulated glucose uptake (MGU) and fasting free fatty acid uptake
(MFFAU). End-diastolic and end-systolic volumes increased and ejection fraction
slightly decreased with both training modes, although no other changes in CMRI
were observed. MFFAU and basal myocardial perfusion remained unchanged. MGU was
decreased by training (HIIT from 46.5 to 35.9; MICT from 47.4 to 44.4 mmol 100 g
1 min-1 , P = 0.007 for time, P = 0.11 for group * time). Adenosine-stimulated
myocardial perfusion responded differently to the training modes (change in mean
HIIT: -19%; MICT: +9%; P = 0.03 for group * time interaction). HIIT and MICT
induce similar metabolic and functional changes in the heart, although myocardial
vascular hyperaemic reactivity is impaired after HIIT. This should be taken into
account when prescribing very intense HIIT for previously untrained subjects.
PMID- 27500952
TI - Hair cortisol concentration and glycated hemoglobin in African American adults.
AB - BACKGROUND: African Americans have higher diabetes prevalence compared to Whites.
They also have elevated cortisol levels - indicating possible HPA axis
dysregulation - which may raise blood glucose as part of the biological response
to physiological and psychosocial stress. Little is known about chronic cortisol
levels in African Americans, and even less about the role of chronically elevated
cortisol in type 2 diabetes development in this racial group. PURPOSE: We used
analysis of cortisol in hair to examine associations of long-term (~3months)
cortisol levels with glycated hemoglobin (HbA1c) in a group of African American
adults. In exploratory analyses, we also studied the relationship of hair
dehydroepiandrosterone (DHEA) with HbA1c. METHOD: Participants were 61 community
dwelling African American adults (85% female; mean age 54.30 years). The first
3cm of scalp-near hair were analyzed for cortisol and DHEA concentration using
enzyme-linked immunoassay analysis. Glycated hemoglobin was assessed, and
regression analyses predicting HbA1c from hair cortisol and DHEA were performed
in the full sample and in a subsample of participants (n=20) meeting the National
Institute of Diabetes and Digestive Kidney Disease (NIDDK) criteria for type 2
diabetes (HbA1c>=6.5%). RESULTS: In the full sample, HbA1c increased with hair
cortisol level (beta=0.22, p=0.04, f(2)=0.10), independent of age, sex, chronic
health conditions, diabetes medication use, exercise, and depressive symptoms. In
the subsample of participants with an HbA1c>=6.5%, hair cortisol was also
positively related to HbA1c (beta=0.45, p=0.04, f(2)=0.32), independent of
diabetes medication use. Glycated hemoglobin was unrelated to hair DHEA in both
the full sample and HbA1c>=6.5% subsample. CONCLUSION: Long-term HPA axis
dysregulation in the form of elevated hair cortisol is associated with elevated
HbA1c in African American adults.
PMID- 27500953
TI - Prevalence of Frailty in Latin America and the Caribbean: A Systematic Review and
Meta-Analysis.
AB - BACKGROUND: Countries in Latin America and the Caribbean (LAC) have experienced a
rapid increase in their proportion of older people. This region is marked by a
high prevalence of chronic diseases and disabilities among aging adults. Frailty
appears in the context of LAC negatively affecting quality of life among many
older people. AIM: To investigate the prevalence of frailty among community
dwelling older people in LAC through a systematic review and meta-analysis.
METHODS: A literature search was performed in indexed databases and in the grey
literature. Studies investigating the prevalence of frailty with representative
samples of community-dwelling older people in Latin America and the Caribbean
were retrieved. Independent investigators carried out the study selection process
and the data extraction. A meta-analysis and meta-regression were performed using
STATA 11 software. The systematic review was registered at the International
Prospective Register of Systematic Reviews under the number CRD42014015203.
RESULTS: A total of 29 studies and 43,083 individuals were included in the
systematic review. The prevalence of frailty was 19.6% (95% CI: 15.4-24.3%) in
the investigated region, with a range of 7.7% to 42.6% in the studies reviewed.
The year of data collection influenced the heterogeneity between the studies.
CONCLUSION: Frailty is very common among older people in LAC. As a result,
countries in the region need to adapt their health and social care systems to
demands of an older population.
PMID- 27500954
TI - Respiratory Syncytial Virus and Other Viral Infections among Children under Two
Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease
Severity.
AB - BACKGROUND: Despite a high burden of respiratory syncytial virus (RSV) infections
among children, data on demographic and clinical characteristics of RSV are
scarce in low and middle income countries. This study aims to describe the viral
etiologies, the demographic, epidemiological, and clinical characteristics of
children under two years of age who were hospitalized with a lower respiratory
tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups,
viral load) and its association with disease severity. METHODS: A prospective
study among children under two years of age, hospitalized with LRTI was conducted
in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009
to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were
collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and
quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and
subgroups. RESULTS: Among 632 cases, 48% were RSV positive. RSV infections
occurred at younger age than three other leading viral infections i.e rhinovirus
(RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly
more frequent in the first 6 months of life. Clinical severity score of RSV
infection was significantly higher than PIV-3 but not for RV or MPV. In
multivariate analysis, RV infection was significantly associated with severity
while RSV infection was not. Among RSV infections, neither viral load nor viral
co-infections were significantly associated with severity. Young age and having
fever at admission were significantly associated with both RSV and LRTI severity.
A shift in RSV subgroup predominance was observed during two consecutive rainy
seasons but was not associated with severity. CONCLUSION: We report etiologies,
the epidemiological and clinical characteristics of LRTI among hospitalized
children under two years of age and risk factors of RSV and LRTI severity.
PMID- 27500955
TI - Intracoronary Delivery of Mitochondria to the Ischemic Heart for
Cardioprotection.
AB - We have previously shown that transplantation of autologously derived,
respiration-competent mitochondria by direct injection into the heart following
transient ischemia and reperfusion enhances cell viability and contractile
function. To increase the therapeutic potential of this approach, we investigated
whether exogenous mitochondria can be effectively delivered through the coronary
vasculature to protect the ischemic myocardium and studied the fate of these
transplanted organelles in the heart. Langendorff-perfused rabbit hearts were
subjected to 30 minutes of ischemia and then reperfused for 10 minutes.
Mitochondria were labeled with 18F-rhodamine 6G and iron oxide nanoparticles. The
labeled mitochondria were either directly injected into the ischemic region or
delivered by vascular perfusion through the coronary arteries at the onset of
reperfusion. These hearts were used for positron emission tomography,
microcomputed tomography, and magnetic resonance imaging with subsequent
microscopic analyses of tissue sections to confirm the uptake and distribution of
exogenous mitochondria. Injected mitochondria were localized near the site of
delivery; while, vascular perfusion of mitochondria resulted in rapid and
extensive dispersal throughout the heart. Both injected and perfused mitochondria
were observed in interstitial spaces and were associated with blood vessels and
cardiomyocytes. To determine the efficacy of vascular perfusion of mitochondria,
an additional group of rabbit hearts were subjected to 30 minutes of regional
ischemia and reperfused for 120 minutes. Immediately following regional ischemia,
the hearts received unlabeled, autologous mitochondria delivered through the
coronary arteries. Autologous mitochondria perfused through the coronary
vasculature significantly decreased infarct size and significantly enhanced post
ischemic myocardial function. In conclusion, the delivery of mitochondria through
the coronary arteries resulted in their rapid integration and widespread
distribution throughout the heart and provided cardioprotection from ischemia
reperfusion injury.
PMID- 27500956
TI - Uropathogenic Escherichia coli Releases Extracellular Vesicles That Are
Associated with RNA.
AB - BACKGROUND: Bacterium-to-host signalling during infection is a complex process
involving proteins, lipids and other diffusible signals that manipulate host cell
biology for pathogen survival. Bacteria also release membrane vesicles (MV) that
can carry a cargo of effector molecules directly into host cells. Supported by
recent publications, we hypothesised that these MVs also associate with RNA,
which may be directly involved in the modulation of the host response to
infection. METHODS AND RESULTS: Using the uropathogenic Escherichia coli (UPEC)
strain 536, we have isolated MVs and found they carry a range of RNA species.
Density gradient centrifugation further fractionated and characterised the MV
preparation and confirmed that the isolated RNA was associated with the highest
particle and protein containing fractions. Using a new approach, RNA-sequencing
of libraries derived from three different 'size' RNA populations (<50nt, 50-200nt
and 200nt+) isolated from MVs has enabled us to now report the first example of a
complete bacterial MV-RNA profile. These data show that MVs carry rRNA, tRNAs,
other small RNAs as well as full-length protein coding mRNAs. Confocal microscopy
visualised the delivery of lipid labelled MVs into cultured bladder epithelial
cells and showed their RNA cargo labelled with 5-EU (5-ethynyl uridine), was
transported into the host cell cytoplasm and nucleus. MV RNA uptake by the cells
was confirmed by droplet digital RT-PCR of csrC. It was estimated that 1% of MV
RNA cargo is delivered into cultured cells. CONCLUSIONS: These data add to the
growing evidence of pathogenic bacterial MV being associated a wide range of
RNAs. It further raises the plausibility for MV-RNA-mediated cross-kingdom
communication whereby they influence host cell function during the infection
process.
PMID- 27500958
TI - Mucin as a diagnostic clue in dermatopathology.
AB - Mucins are high-molecular weight glycoproteins typically found in normal skin in
small amounts. There are several reports regarding different types of cutaneous
mucinosis. In this report, we discuss mucins in dermatopathology as a diagnostic
clue of some well-known entities and some less frequent cutaneous diseases. We
also emphasize mucin as a sign in the differential diagnosis between conditions
that show histopathological overlap. Lastly, we discuss the locations and
circumstances in which mucin could be considered almost normal or physiological.
PMID- 27500957
TI - Human Rabies in China, 1960-2014: A Descriptive Epidemiological Study.
AB - BACKGROUND: Rabies in China remains a public health problem. In 2014, nearly one
thousand rabies-related deaths were reported while rabies geographic distribution
has expanded for the recent years. This report used surveillance data to describe
the epidemiological characteristics of human rabies in China including
determining high-risk areas and seasonality to support national rabies prevention
and control activities. METHODS: We analyzed the incidence and distribution of
human rabies cases in mainland China using notifiable surveillance data from 1960
2014, which includes a detailed analysis of the recent years from 2004 to 2014.
RESULTS: From 1960 to 2014, 120,913 human rabies cases were reported in mainland
China. The highest number was recorded in 1981(0.7/100,000; 7037 cases), and in
2007(0.3/100,000; 3300 cases). A clear seasonal pattern has been observed with a
peak in August (11.0% of total cases), Human rabies cases were reported in all
provinces with a yearly average of 2198 from 1960 to 2014 in China, while the
east and south regions were more seriously affected compared with other regions.
From2004 to 2014, although the number of cases decreased by 65.2% since 2004 from
2651 to 924 cases, reported areas has paradoxically expanded from 162 prefectures
to 200 prefectures and from southern to the central and northern provinces of
China. Farmers accounted most of the cases (65.0%); 50-59 age group accounted for
the highest proportion (20.5%), and cases are predominantly males with a male-to
female ratio of 2.4:1 on average. CONCLUSIONS: Despite the overall steady decline
of cases since the peak in 2007, the occurrence of cases in new areas and the
spread trend were obvious in China in recent years. Further investigations and
efforts are warranted in the areas have high rabies incidence to control rabies
by interrupting transmission from dogs to humans and in the dog population.
Furthermore, elimination of rabies should be eventually the ultimate goal for
China.
PMID- 27500959
TI - Cost of microbial larviciding for malaria control in rural Tanzania.
AB - OBJECTIVE: Microbial larviciding may be a potential supplement to conventional
malaria vector control measures, but scant information on its relative
implementation costs and effectiveness, especially in rural areas, is an
impediment to expanding its uptake. We perform a costing analysis of a seasonal
microbial larviciding programme in rural Tanzania. METHODS: We evaluated the
financial and economic costs from the perspective of the public provider of a 3
month, community-based larviciding intervention implemented in twelve villages in
the Mvomero District of Tanzania in 2012-2013. Cost data were collected from
financial reports and invoices and through discussion with programme
administrators. Sensitivity analysis explored the robustness of our results to
varying key parameters. RESULTS: Over the 2-year study period, approximately 6873
breeding sites were treated with larvicide. The average annual economic costs of
the larviciding intervention in rural Tanzania are estimated at 2014 US$ 1.44 per
person protected per year (pppy), US$ 6.18 per household and US$ 4481.88 per
village, with the larvicide and staffing accounting for 14% and 58% of total
costs, respectively. CONCLUSIONS: We found the costs pppy of implementing a
seasonal larviciding programme in rural Tanzania to be comparable to the costs of
other larviciding programmes in urban Tanzania and rural Kenya. Further research
should evaluate the cost-effectiveness of larviciding relative to, and in
combination with, other vector control strategies in rural settings.
PMID- 27500960
TI - Anterior Perineal PlanE for ultra-low Anterior Resection of the rectum (APPEAR)
technique: A systematic review.
AB - INTRODUCTION: The Anterior Perineal PlanE for ultra-low Anterior Resection of the
rectum (APPEAR) technique utilises a perineal incision to facilitate resection of
the distal rectum. The aim of this study was to review use of the APPEAR
technique, assessing patient selection, indications, complications and outcomes,
both oncological and functional. MATERIALS AND METHODS: A systematic review was
carried out to identify studies reporting outcomes following rectal resection via
an anterior perineal incision, with no limits on year or language. All studies
were included. Quality of studies was assessed using the methodological index for
non-randomised studies (MINORS) score. RESULTS: Thirteen studies were identified
from 1985 to 2013. 174 patients (102 male), ranging from 21 to 82 years,
underwent surgery at eleven centres in seven countries. Maximum experience at one
centre is 60 cases. 9 cases were performed for rectal dysplasia, 141 for rectal
cancer; 96 resections were R0 (remaining 45 unstated). 14 cases were carried out
laparoscopically. 30-day mortality was 2.3% (4 patients); there were 2 further
deaths from systemic recurrence. Permanent stoma rate was 8/155 (5%). The most
frequent complication was perineal or vaginal fistulation (26 patients): 6
underwent reoperation; 15 healed with conservative management; 5 required a
permanent stoma. Functional outcomes were variably reported; median stool
frequency was 3/24hrs with average Wexner scores of 5-5.5. CONCLUSION: In
selected patients the APPEAR technique offers avoidance of permanent colostomy
with good oncological outcomes. The majority of studies had short follow up
periods and longer-term outcomes will need evaluation.
PMID- 27500961
TI - Robot-assisted partial nephrectomy.
AB - Partial nephrectomy is the standard treatment for small renal masses. Currently,
it is commonly performed using minimally invasive approaches, including
laparoscopic and robot-assisted techniques. The aim of the present review is to
report the surgical technique of robot-assisted partial nephrectomy in full
detail as well as available literature results.
PMID- 27500962
TI - Massive and recurrent diverticular hemorrhage, risk factors and treatment.
AB - AIM: Diverticular hemorrhage may be massive or recurrent, requiring surgical
management. The aim of our study is to define risk factors that predict
rebleeding or need for urgent operation in patients with diverticular hemorrhage.
METHODS: Retrospective study was conducted on patients who were admitted for
diverticular hemorrhage. Data pertaining to patient and bleeding characteristics,
method of diagnosis, blood transfusion and type of operation were collected.
Multivariate analysis model compared patients who experienced single bleeding
episode with those with recurrent episodes, and patients who underwent surgery
with those who did not. RESULTS: One hundred and four patients met the inclusion
criteria. Thirty four patients experienced more than one bleeding episode. Ten
patients needed surgery for recurrent bleeding. Five patients presented with
hemodynamic instability, none of them required surgical treatment. Neither
patients' comorbidity nor anticoagulant and antiaggregant treatments were
associated with increased risk for recurrent hemorrhage. Diabetes mellitus was
correlated with decreased risk for recurrent hemorrhage, OR = 0.21, (CI 95% (0.06
0.73)); p = 0.014. Independent risk factor for massive recurrent diverticular
hemorrhage requiring surgery was right sided diverticulosis, OR = 4.6(CI 95% (2.1
19)); p = 0.006. CONCLUSIONS: Right colon diverticulosis rather than patient
characteristics and medical treatment should prompt for aggressive management
with lower threshold for surgical intervention.
PMID- 27500963
TI - Cryoablation of small kidney tumors.
AB - INTRODUCTION: Cryoablation (CA) has been broadly used mostly in the treatment of
small renal masses (SRMs). The present review aims to define the current role of
CA in the treatment of SRMs by assessing clinical indications and outcomes.
METHOD: A comprehensive review on patient selection, procedural details,
perioperative complications, and short/long-term oncological and functional
outcomes was conducted. For each section, a take-home message was formulated with
level of evidence (LoE) according to Cochrane collaboration. RESULTS: Age and
comorbidity drive the choice of ablation in SRMs, although hospital setting also
influences the decision. Technically in adequate CA or first post-CA control
occurs in 3-5% of laparoscopic cryoablation (LCA) or percutaneous cryoablation
(PCA) series. Meta-analysis does not evidence differences in the rate of residual
tumor per person-year between the approaches (0.033 LCA vs. 0.046 PCA, p = 0.25).
Perioperative complications (8-25%) are erratically reported. LCA has
significantly lower likelihood of complications than minimally invasive partial
nephrectomy (MIPN). Systematic reviews indicate 30-month local tumor progression
rate of 8.5% for LCA in renal cell carcinoma but low metastatic progression (1
4.4%). Few LCA long-term follow-up series (mean/media 48-98 months) report
recurrence-free survival (RFS) and cancer-specific survival (CSS) ranges of 80
100%. For PCA, Kaplan-Meier local disease-free survival (DFS) of 95.6% at 3-5
years [32] and 5-year overall survival and local RFS of 86.3% were reported. The
decrease in renal function after CA is minimal, and the only risk factor
associated is the basal estimated glomerular filtration rate (eGFR). CONCLUSION:
LoE 3a/b confirms lower CA perioperative complication rate and higher local
progression rate than those for MIPN. CA preserves postoperative renal
functional, without any evidence of differences in mid-/long-term follow-up
compared to nephron sparing surgery.
PMID- 27500964
TI - Special considerations for the management of pediatric acute respiratory distress
syndrome.
AB - INTRODUCTION: Pediatric acute respiratory distress syndrome (ARDS) remains a
diagnostic and therapeutic challenge with significant mortality and morbidity.
There are limited data to guide identification and management. AREAS COVERED: The
Pediatric Acute Lung Injury Consensus Conference recently proposed pediatric
specific definitions for ARDS and management recommendations. In this review, we
discuss aspects of pediatric ARDS that have received more attention over the past
few years: high frequency oscillatory ventilation, administration of
corticosteroids and functional outcomes. We conducted searches on PubMed,
ClinicalKey and Google Scholar using medical subject heading terms and text words
related to acute lung injury and ARDS. Expert commentary: The newly proposed
definition for pediatric ARDS requires validation for efficacy in diagnosis and
risk stratification. At present, there is insufficient evidence to support
routine use of high frequency oscillatory ventilation or corticosteroids in
pediatric ARDS. Further studies are required to determine the impact of pediatric
ARDS on functional outcomes.
PMID- 27500966
TI - New insights in the homotopic and heterotopic connectivity of the frontal portion
of the human corpus callosum revealed by microdissection and diffusion
tractography.
AB - Extensive studies revealed that the human corpus callosum (CC) plays a crucial
role in providing large-scale bi-hemispheric integration of sensory, motor and
cognitive processing, especially within the frontal lobe. However, the literature
lacks of conclusive data regarding the structural macroscopic connectivity of the
frontal CC. In this study, a novel microdissection approach was adopted, to
expose the frontal fibers of CC from the dorsum to the lateral cortex in eight
hemispheres and in one entire brain. Post-mortem results were then combined with
data from advanced constrained spherical deconvolution in 130 healthy subjects.
We demonstrated as the frontal CC provides dense inter-hemispheric connections.
In particular, we found three types of fronto-callosal fibers, having a dorso
ventral organization. First, the dorso-medial CC fibers subserve homotopic
connections between the homologous medial cortices of the superior frontal gyrus.
Second, the ventro-lateral CC fibers subserve homotopic connections between
lateral frontal cortices, including both the middle frontal gyrus and the
inferior frontal gyrus, as well as heterotopic connections between the medial and
lateral frontal cortices. Third, the ventro-striatal CC fibers connect the medial
and lateral frontal cortices with the contralateral putamen and caudate nucleus.
We also highlighted an intricate crossing of CC fibers with the main association
pathways terminating in the lateral regions of the frontal lobes. This combined
approach of ex vivo microdissection and in vivo diffusion tractography allowed
demonstrating a previously unappreciated three-dimensional architecture of the
anterior frontal CC, thus clarifying the functional role of the CC in mediating
the inter-hemispheric connectivity. Hum Brain Mapp 37:4718-4735, 2016. (c) 2016
Wiley Periodicals, Inc.
PMID- 27500965
TI - Aging and peripheral lipopolysaccharide can modulate epigenetic regulators and
decrease IL-1beta promoter DNA methylation in microglia.
AB - In aged mice, peripheral stimulation of the innate immune system with
lipopolysaccharide (LPS) causes exaggerated neuroinflammation and prolonged
sickness behavior due in part to microglial dysfunction. Epigenetic changes to
DNA may play a role in microglial dysfunction; therefore, we sought to determine
whether aged microglia displayed DNA hypomethylation of the interleukin-1 beta
(IL-1beta) promoter and altered expression of epigenetic regulators. We further
examined whether the demethylating agent 5-azacytidine induced IL-1beta
expression in BV2 and primary microglia similar to microglia from aged mice.
Novel findings indicated that aged mice had decreased methylation of the IL-1beta
gene promoter in primary microglia basally or following systemic LPS that is
associated with increased IL-1beta mRNA, intracellular IL-1beta production, as
well as prolonged sickness behavior. Last, 5-azacytidine increased IL-1beta gene
expression and decreased DNA methylation of BV2 and primary microglial cells
similar to microglia from aged mice. Taken together, these data indicate that DNA
methylation promotes heightened microglial activation in the aged brain.
PMID- 27500967
TI - ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in
cohort of patients from North India.
AB - ALK gene rearrangement in the lung adenocarcinomas is the second most common (1.6
11.7% of NSCLC) targetable genomic change after EGFR mutations. However, the
prevalence and clinicopathological features of ALK-rearranged lung
adenocarcinomas from North India are lacking. A total of 240 cases of lung
adenocarcinoma were screened for EGFR mutations and for ALK expression. Smoking
status, TNM stage, and treatment response were recorded in all cases. Out of 240
cases screened, 37 cases were positive for EGFR mutations and 17 cases (7.08%)
showed ALK positivity with immunohistochemistry and break-apart FISH. On
excluding 37 EGFR mutation-positive cases, the incidence of ALK-positive
adenocarcinoma appears to be higher (17/203 cases, 8.03%). Eight were men and
nine were women with mean age of 51.7 years. Majority (62.5%) were non-smokers
and had unresectable disease (70.6% stage IV, 17.6% IIIB). The morphological
patterns noted were solid (12 cases), papillary (four cases), and micropapillary
(one case). Signet ring (two cases) and clear cell change (one cases) were noted.
Out of five patients who received crizotinib, three had partial response and two
had stable disease. ALK-rearranged lung adenocarcinomas account for a minor
proportion of NSCLC with prevalence similar to that reported in literature.
However, as contrast to published data in our series, patients were in older age
group and had solid and papillary pattern on morphology with an aggressive
course.
PMID- 27500968
TI - Role of gamma-glutamyl cyclotransferase as a therapeutic target for colorectal
cancer based on the lentivirus-mediated system.
AB - Human GGCT (gamma-glutamyl cyclotransferase) has been shown to be upregulated in
most tumors, but its role in colorectal cancer (CRC) is poorly understood. Thus,
CRC cell lines, including HCT116 and SW1116, were chosen to investigate the role
of GGCT by constructing a GGCT silencing cells model using lentivirus-mediated
RNA interference. The knockdown efficiency was confirmed by reverse transcription
quantitative PCR and a western blot assay. Then, a set of biological functions of
GGCT silencing on CRC cell was assessed by MTT, colony-formation assay, and flow
cytometry analysis. Further, western blot and Pathscan intracellular signaling
were used to detect intracellular signaling associated with cell growth and
apoptosis induced by GGCT knockdown. In addition, the clinical chemotherapeutic
drug 5-fluorouracil was used to investigate the impact of GGCT silencing on drug
sensitivity by an Annexin V/7-AAD double-staining assay. The results of the
analysis indicated that GGCT silencing significantly suppressed cell
proliferation and arrested cell cycle at the G0/G1 phase by regulating the
expression of p21, p27, and cyclin E. Moreover, GGCT silencing triggered the
apoptosis of CRC cells by activating caspase-3 and cleaved poly-ADP-ribose
polymerase pathways and downregulating the phosphorylation proline-rich Akt
substrate of 40 kDa (PRAS40) expression levels. Furthermore, GGCT silencing
combined with 5-fluorouracil treatment further induced the apoptotic rate of CRC
cells. These findings suggest that GGCT may be a promising diagnostic and
therapeutic target for CRC by activating the apoptotic pathway.
PMID- 27500969
TI - Psychometric Properties of the Dutch Depression Stigma Scale (DSS) and
Associations with Personal and Perceived Stigma in a Depressed and Community
Sample.
AB - BACKGROUND: Research on depression stigma is needed to gain more insight into the
underlying construct and to reduce the level of stigma in the community. However,
few validated measurements of depression stigma are available in the Netherlands.
Therefore, this study first sought to examine the psychometric properties of the
Dutch translation of the Depression Stigma Scale (DSS). Second, we examined which
demographic (gender, age, education, partner status) and other variables (anxiety
and knowledge of depression) are associated with personal and perceived stigma
within these samples. METHODS: The study population consisted of an adult
convenience sample (n = 253) (study 1) and a community adult sample with elevated
depressive symptoms (n = 264) (study 2). Factor structure, internal consistency,
and validity were assessed. The associations between stigma, demographic
variables and anxiety level were examined with regression analyses. RESULTS:
Confirmatory factor analysis supported the validity and internal consistency of
the DSS personal stigma scale. Internal consistency was sufficient (Cronbach's
alpha = .70 (study 1) and .77 (study 2)). The results regarding the perceived
stigma scale revealed no clear factor structure. Regression analyses showed that
personal stigma was higher in younger people, those with no experience with
depression, and those with lower education. CONCLUSIONS: This study established
the validity and internal consistency of the DSS personal scale in the
Netherlands, in a community sample and in people with elevated depressive
symptoms. However, additional research is needed to examine the factor structure
of the DSS perceived scale and its use in other samples.
PMID- 27500970
TI - Prophylactic Gentamicin Is Not Associated with Acute Kidney Injury in Patients
with Open Fractures.
AB - BACKGROUND: Data on antimicrobial prophylaxis for open fractures is limited, with
many protocols based on expert recommendations. These protocols include
aminoglycosides (AGs) for fractures with significant soft tissue injury, but
these drugs are associated with acute kidney injury (AKI) in other settings; this
risk has not been defined for open fracture prophylaxis. METHODS: We performed a
retrospective study from May 2012 to October 2014 at our Level 1 trauma center.
Patients with open fractures were evaluated for demographics, location/type of
fracture, injury severity, and receipt of an AG. Outcomes included rates of AKI,
infection, and mortality. RESULTS: There were 167 patients with open fractures
during the study period (119 males, mean age 42 +/- 17 [standard deviation]
years), with 80 (48%) receiving prophylactic gentamicin (AG+ group). The AG+ and
AG- patients had similar fracture sites and Injury Severity Scores (ISSs) (12.6
+/- 9.9 AG+ vs. 15.9 +/- 13.2 AG-) but were more likely to have sustained blunt
trauma (96% AG+ vs. 77%; p < 0.001) or received intravenous contrast medium <=48
h from admission (75% AG+ vs. 56% AG-; p = 0.01). Gentamicin was not associated
with AKI (odds ratio [OR] 0.22; 95% confidence interval [CI] 0.020-2.44; p =
0.22), whereas hypotension on admission (OR 10.7; 95% CI 1.42-80.93; p = 0.02)
and ISS (OR 1.1; 95% CI 1.01-1.20; p = 0.02) were both associated with AKI. Only
four fracture site infections were identified, three in the AG+ group and one in
the AG- group (3.8% vs. 1.1%; p = 0.27). The mortality rate was greater in the AG
group (3.8% vs. 12.6%; p = 0.04). CONCLUSIONS: Prophylactic gentamicin is not
associated with AKI, whereas hypotension on admission and higher ISS were. The
use of nephrotoxic agents, including aminoglycosides, should be restricted in
open fracture patients presenting with hypotension or a high ISS.
PMID- 27500971
TI - Environmental variability and the evolution of the glucocorticoid receptor
(Nr3c1) in African starlings.
AB - One of the primary ways that organisms cope with environmental change is through
regulation of the hypothalamo-pituitary-adrenal (HPA) axis, the neuroendocrine
system that controls reactions to stress. Variation in genes regulating the HPA
axis - particularly the glucocorticoid receptor - may facilitate adaptation to
changing climatic conditions by altering expression. Here we examine signatures
of selection on the glucocorticoid receptor gene (Nr3c1) in African starlings
that inhabit a range of environments, including those with variable climatic
conditions. To investigate potential adaptive mechanisms underlying the
vertebrate stress response, we sequence the Nr3c1 gene in 27 species of African
starlings. Although we find some evidence of positive selection, substitution
rate is negatively correlated with variance in precipitation. This suggests
climatic cycling in sub-Saharan Africa may have resulted in lower substitution
rates to maintain a successful coping strategy. When environmental conditions
fluctuate rapidly, variation in the strength of purifying selection can explain
evolutionary rate variation.
PMID- 27500972
TI - Development of an Insert Co-culture System of Two Cellular Types in the Absence
of Cell-Cell Contact.
AB - The role of secreted soluble factors in the modification of cellular responses is
a recurrent theme in the study of all tissues and systems. In an attempt to make
straightforward the very complex relationships between the several cellular
subtypes that compose multicellular organisms, in vitro techniques have been
developed to help researchers acquire a detailed understanding of single cell
populations. One of these techniques uses inserts with a permeable membrane
allowing secreted soluble factors to diffuse. Thus, a population of cells grown
in inserts can be co-cultured in a well or dish containing a different cell type
for evaluating cellular changes following paracrine signaling in the absence of
cell-cell contact. Such insert co-culture systems offer various advantages over
other co-culture techniques, namely bidirectional signaling, conserved cell
polarity and population-specific detection of cellular changes. In addition to
being utilized in the field of inflammation, cancer, angiogenesis and
differentiation, these co-culture systems are of prime importance in the study of
the intricate relationships that exist between the different cellular subtypes
present in the central nervous system, particularly in the context of
neuroinflammation. This article offers general methodological guidelines in order
to set up an experiment in order to evaluating cellular changes mediated by
secreted soluble factors using an insert co-culture system. Moreover, a specific
protocol to measure the neuroinflammatory effects of cytokines secreted by
lipopolysaccharide-activated N9 microglia on neuronal PC12 cells will be
detailed, offering a concrete understanding of insert co-culture methodology.
PMID- 27500973
TI - Modeling zero-modified count and semicontinuous data in health services research
part 2: case studies.
AB - This article is the second installment of a two-part tutorial on the analysis of
zero-modified count and semicontinuous data. Part 1, which appears as a companion
piece in this issue of Statistics in Medicine, provides a general background and
overview of the topic, with particular emphasis on applications to health
services research. Here, we present three case studies highlighting various
approaches for the analysis of zero-modified data. The first case study describes
methods for analyzing zero-inflated longitudinal count data. Case study 2
considers the use of hurdle models for the analysis of spatiotemporal count data.
The third case study discusses an application of marginalized two-part models to
the analysis of semicontinuous health expenditure data. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27500974
TI - Pathway-Dependent Post-assembly Modification of an Anthracene-Edged M(II)4L6
Tetrahedron.
AB - Fe(II)4L6 tetrahedral cage 1 undergoes post-assembly modification (PAM) via a
Diels-Alder cycloaddition of the anthracene panels of the cage with
tetracyanoethylene (TCNE). The modified cage 2 possesses an enclosed cavity
suitable for encapsulation of the fullerene C60, whereas original cage 1 forms a
unique covalent adduct through a Diels-Alder cycloaddition of three of its
anthracene ligands with C60. This adduct undergoes further PAM via reaction of
the remaining three ligands with TCNE, enabling the isolation of two distinct
products depending on the order of addition of C60 and TCNE. Modified cage 2 was
also able to bind an anionic guest, [Co(C2B9H11)2](-), which was not encapsulated
by the original cage, demonstrating the potential of PAM for tuning the binding
properties of supramolecular hosts.
PMID- 27500975
TI - Fabrication of Fully Solution Processed Inorganic Nanocrystal Photovoltaic
Devices.
AB - We demonstrate a method for the preparation of fully solution processed inorganic
solar cells from a spin and spray coating deposition of nanocrystal inks. For the
photoactive absorber layer, colloidal CdTe and CdSe nanocrystals (3-5 nm) are
synthesized using an inert hot injection technique and cleaned with
precipitations to remove excess starting reagents. Similarly, gold nanocrystals
(3-5 nm) are synthesized under ambient conditions and dissolved in organic
solvents. In addition, precursor solutions for transparent conductive indium tin
oxide (ITO) films are prepared from solutions of indium and tin salts paired with
a reactive oxidizer. Layer-by-layer, these solutions are deposited onto a glass
substrate following annealing (200-400 degrees C) to build the nanocrystal solar
cell (glass/ITO/CdSe/CdTe/Au). Pre-annealing ligand exchange is required for CdSe
and CdTe nanocrystals where films are dipped in NH4Cl:methanol to replace long
chain native ligands with small inorganic Cl(-) anions. NH4Cl(s) was found to act
as a catalyst for the sintering reaction (as a non-toxic alternative to the
conventional CdCl2(s) treatment) leading to grain growth (136+/-39 nm) during
heating. The thickness and roughness of the prepared films are characterized with
SEM and optical profilometry. FTIR is used to determine the degree of ligand
exchange prior to sintering, and XRD is used to verify the crystallinity and
phase of each material. UV/Vis spectra show high visible light transmission
through the ITO layer and a red shift in the absorbance of the cadmium
chalcogenide nanocrystals after thermal annealing. Current-voltage curves of
completed devices are measured under simulated one sun illumination. Small
differences in deposition techniques and reagents employed during ligand exchange
have been shown to have a profound influence on the device properties. Here, we
examine the effects of chemical (sintering and ligand exchange agents) and
physical treatments (solution concentration, spray-pressure, annealing time and
annealing temperature) on photovoltaic device performance.
PMID- 27500976
TI - Cross-Correlated Relaxation of Dipolar Coupling and Chemical-Shift Anisotropy in
Magic-Angle Spinning R1rho NMR Measurements: Application to Protein Backbone
Dynamics Measurements.
AB - Transverse relaxation rate measurements in magic-angle spinning solid-state
nuclear magnetic resonance provide information about molecular motions occurring
on nanosecond-to-millisecond (ns-ms) time scales. The measurement of
heteronuclear ((13)C, (15)N) relaxation rate constants in the presence of a spin
lock radiofrequency field (R1rho relaxation) provides access to such motions, and
an increasing number of studies involving R1rho relaxation in proteins have been
reported. However, two factors that influence the observed relaxation rate
constants have so far been neglected, namely, (1) the role of CSA/dipolar cross
correlated relaxation (CCR) and (2) the impact of fast proton spin flips (i.e.,
proton spin diffusion and relaxation). We show that CSA/D CCR in R1rho
experiments is measurable and that the CCR rate constant depends on ns-ms
motions; it can thus provide insight into dynamics. We find that proton spin
diffusion attenuates this CCR due to its decoupling effect on the doublet
components. For measurements of dynamics, the use of R1rho rate constants has
practical advantages over the use of CCR rates, and this article reveals factors
that have so far been disregarded and which are important for accurate
measurements and interpretation.
PMID- 27500977
TI - Population structure from NOS genes correlates with geographical differences in
coronary incidence across Europe.
AB - OBJECTIVES: The population analysis of cardiovascular risk and non-risk genetic
variation can help to identify adaptive or random demographic processes that
shaped coronary incidence variation across geography. MATERIAL AND METHODS: In
this study, 114 single nucleotide polymorphisms and 17 tandem repeat
polymorphisms from Nitric Oxide Synthases (NOS) regions were analyzed in 1686
individuals from 35 populations from Europe, North Africa, and the Middle East.
NOS genes encode for key enzymes on nitric oxide availability, which is involved
in several cardiovascular processes. These genetic variations were used to test
for selection and to infer the population structure of NOS regions. Moreover, we
tested whether the variation in the incidence of coronary events and in the
levels of classical risk factors in 11 of these European populations could be
explained by the population structure estimates. RESULTS: Our results supported,
first, the absence of clear signs of selection for NOS genetic variants
associated with cardiovascular diseases, and second, the presence of a continuous
genetic pattern of variation across European and North African populations
without a Mediterranean barrier for gene flow. Finally, population structure
estimates from NOS regions are closely correlated with coronary event rates and
classical risk parameters (explaining 39-98%) among European populations.
CONCLUSION: Our results reinforce the hypothesis that genetic bases of
cardiovascular diseases and associated complex phenotypes could be geographically
shaped by random demographic processes.
PMID- 27500978
TI - Midazolam-ketamine dual therapy stops cholinergic status epilepticus and reduces
Morris water maze deficits.
AB - OBJECTIVE: Pharmacoresistance remains an unsolved therapeutic challenge in status
epilepticus (SE) and in cholinergic SE induced by nerve agent intoxication. SE
triggers a rapid internalization of synaptic gamma-aminobutyric acid A (GABAA )
receptors and externalization of N-methyl-d-aspartate (NMDA) receptors that may
explain the loss of potency of standard antiepileptic drugs (AEDs). We
hypothesized that a drug combination aimed at correcting the consequences of
receptor trafficking would reduce SE severity and its long-term consequences.
METHODS: A severe model of SE was induced in adult Sprague-Dawley rats with a
high dose of lithium and pilocarpine. The GABAA receptor agonist midazolam, the
NMDA receptor antagonist ketamine, and/or the AED valproate were injected 40 min
after SE onset in combination or as monotherapy. Measures of SE severity were the
primary outcome. Secondary outcomes were acute neuronal injury, spontaneous
recurrent seizures (SRS), and Morris water maze (MWM) deficits. RESULTS:
Midazolam-ketamine dual therapy was more efficient than double-dose midazolam or
ketamine monotherapy or than valproate-midazolam or valproate-ketamine dual
therapy in reducing several parameters of SE severity, suggesting a synergistic
mechanism. In addition, midazolam-ketamine dual therapy reduced SE-induced acute
neuronal injury, epileptogenesis, and MWM deficits. SIGNIFICANCE: This study
showed that a treatment aimed at correcting maladaptive GABAA receptor and NMDA
receptor trafficking can stop SE and reduce its long-term consequences. Early
midazolam-ketamine dual therapy may be superior to monotherapy in the treatment
of benzodiazepine-refractory SE.
PMID- 27500979
TI - Catalyst-Free Difunctionalization of Activated Alkenes in Water: Efficient
Synthesis of beta-Keto Sulfides and Sulfones.
AB - Difunctionalization of activated alkenes, a powerful strategy in chemical
synthesis, has been accomplished for direct synthesis of a series of beta-keto
sulfides and beta-keto sulfones. The transformation, mediated by O2 , proceeds
smoothly in water and without any catalyst. Prominent advantages of this method
include mild reaction conditions, purification simplicity, and gram-scale
synthesis, underlining the practical utility of this methodology.
PMID- 27500980
TI - Porous Coordination Polymer Based on Bipyridinium Carboxylate Linkers with High
and Reversible Ammonia Uptake.
AB - The zwitterionic bipyridinium carboxylate ligand 1,1'-bis(4-carboxyphenyl)-4,4'
bipyridinium (pc1) in the presence of cadmium chloride affords novel porous
coordination polymers (PCPs): [Cd4(pc1)3Cl6].CdCl4.guest (1) crystallizing in the
P31c space group. In the structure, [Cd4Cl6(CO2)6] building units are linked
together by six pc1 ligands, leading to a 3D high-symmetrical network exhibiting
hexagonal channels along the c axis. The walls of this PCP consist of cationic
electron-acceptor bipyridinium units. The PCP 1 reversibly adsorbs H2O and CH3OH
up to about 0.1 g/g at saturation showing the adsorption isotherms characteristic
of a moderately hydrophilic sorbent. Adsorption of ammonia (NH3) follows a
different pattern, reaching an exceptional uptake of 0.39 g/g (22.3 mmol/g) after
the first adsorption cycle. Although the crystalline structure of 1 collapses
after the first adsorption, the solid can be regenerated and maintains the
capacity of 0.29 g/g (17 mmol/g) in the following cycles. We found that the high
NH3 uptake is due to a combination of pore filling taking place below 150 h.Pa
and chemisorption occurring at higher pressures. The latter process was shown to
involve two phenomena: (i) coordination of NH3 molecules to Cd(2+) cations as
follows from (113)Cd NMR and (ii) strong donor-acceptor interactions between NH3
molecules and pc1 ligands.
PMID- 27500981
TI - Mitigation of Ventilator-induced Diaphragm Atrophy by Transvenous Phrenic Nerve
Stimulation.
AB - RATIONALE: Ventilator-induced diaphragm dysfunction is a significant contributor
to weaning difficulty in ventilated critically ill patients. It has been
hypothesized that electrically pacing the diaphragm during mechanical ventilation
could reduce diaphragm dysfunction. OBJECTIVES: We tested a novel, central line
catheter-based, transvenous phrenic nerve pacing therapy for protecting the
diaphragm in sedated and ventilated pigs. METHODS: Eighteen Yorkshire pigs were
studied. Six pigs were sedated and mechanically ventilated for 2.5 days with
pacing on alternate breaths at intensities that reduced the ventilator pressure
time product by 20-30%. Six matched subjects were similarly sedated and
ventilated but were not paced. Six pigs served as never-ventilated, never-paced
control animals. MEASUREMENTS AND MAIN RESULTS: Cumulative duration of pacing
therapy ranged from 19.7 to 35.7 hours. Diaphragm thickness assessed by
ultrasound and normalized to initial value showed a significant decline in
ventilated-not paced but not in ventilated-paced subjects (0.84 [interquartile
range (IQR), 0.78-0.89] vs. 1.10 [IQR, 1.02-1.24]; P = 0.001). Compared with
control animals (24.6 MUm2/kg; IQR, 21.6-26.0), median myofiber cross-sectional
areas normalized to weight and sarcomere length were significantly smaller in the
ventilated-not paced (17.9 MUm2/kg; IQR, 15.3-23.7; P = 0.005) but not in the
ventilated-paced group (24.9 MUm2/kg; IQR, 16.6-27.3; P = 0.351). After 60 hours
of mechanical ventilation all six ventilated-paced subjects tolerated 8 minutes
of intense phrenic stimulation, whereas three of six ventilated-not paced
subjects did not (P = 0.055). There was a nonsignificant decrease in diaphragm
tetanic force production over the experiment in the ventilated-paced and
ventilated-not paced groups. CONCLUSIONS: These results suggest that early
transvenous phrenic nerve pacing may mitigate ventilator-induced diaphragm
dysfunction.
PMID- 27500982
TI - Morphogenesis of the middle ear ossicles and spatial relationships with the
external and inner ears during the embryonic period.
AB - We describe the three-dimensional morphogenesis of the middle ear ossicles (MEOs)
according to Carnegie stage (CS) in human embryos. Seventeen samples including 33
MEOs from CS18 to 23 were selected from the Kyoto Collection. The primordia of
the MEOs and related structures were histologically observed and three
dimensionally reconstructed from digital images. The timing of chondrogenesis was
variable among structures. The stapes was recognizable as a vague condensation of
the mesenchymal cells in all samples from CS18, whereas the malleus and incus
were recognizable at CS19. Chondrogenesis of all MEOs was evident in all samples
after CS21. The chondrocranium was recognizable in all samples by CS18, and the
perichondrium border of the auricular cartilage and otic capsule was distinct in
all samples at CS23. At CS19, the MEOs were positioned in the anterior to
posterior direction, following the order malleus, incus, stapes, which adjusted
gradually during development. The MEOs connected in all samples after CS22. The
stapes was located close to the vestibular part of the inner ear, although the
basal part was not differentiated into the "footplate" form, even at CS23. The
handles of the malleus were close to the tubotympanic recess at CS23, but were
distant from the external auditory meatus. Determining the timeline of the
formation of MEOs and connection of the external and inner ears can be
informative for understanding hearing loss caused by failure of this connection.
These data may provide a useful standard for morphogenesis, and will contribute
to distinguishing between normal and abnormal MEO development. Anat Rec, 299:1325
1337, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27500984
TI - The Editor recommends this issue's article to the reader: Adhesive systems for
restoring primary teeth: a systematic review and meta-analysis of in vitro
studies.
PMID- 27500983
TI - Factor affecting happiness among nursing students in South Korea.
AB - WHAT IS KNOWN ON THE SUBJECT?: Despite the increased interest in nursing
students' happiness in South Korea, few studies have attempted to identify
factors influencing their happiness. Therefore, nursing educators should
consistently investigate the factors influencing happiness and develop strategies
to improve happiness among Korean nursing students. WHAT THIS PAPER ADDS TO
EXISTING KNOWLEDGE?: This study confirmed that there were positive correlations
between grateful disposition, social support and happiness. In addition, grateful
disposition and support from intimate people were identified as predictors of
happiness in Korean nursing students. WHAT ARE THE IMPLICATIONS FOR PRACTICE?:
Development of intervention programmes to help nursing students increase grateful
disposition and support from intimate people may be helpful for improving
happiness. These programmes can include activity, such as writing a gratitude
journal, and extracurricular programmes, such as mentoring programmes between
seniors and juniors and/or professor and student. ABSTRACT: Introduction
Happiness is very important in the training and development of nursing students
as future nurses. However, nursing students experience a high level of stress and
low level of happiness in South Korea. Aim This study aimed to investigate
factors that affect happiness among nursing students in South Korea. Method Data
were collected from a total of 241 nursing enrolled in two 4-year baccalaureate
nursing programmes in South Korea, using a self-administrated questionnaire. To
identify predictors of happiness, stepwise regression analysis was conducted.
Results The results indicated that grateful disposition and support from intimate
people significantly predict happiness among Korean nursing students. These two
factors accounted for 38.0% of the variance in happiness. Discussion This study
indicated grateful disposition and support from intimate people as factors
promoting happiness in nursing students. The findings highlight grateful
disposition and support from intimate people as important factors when developing
effective interventions that foster nursing students' happiness.
PMID- 27500985
TI - Diagnostic accuracy of intracranial translucency in detecting spina bifida: a
systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the diagnostic accuracy of intracranial translucency (IT)
in the detection of spina bifida (SB) in the first trimester of pregnancy.
METHODS: We included study assessing the accuracy of sonographic measurements of
IT in a mid-sagittal view of the fetal face in prediction of SB in the first
trimester of pregnancy. The primary outcome was the accuracy of IT in prediction
of spina bifida. Summary estimates of sensitivity, specificity, positive and
negative likelihood ratios (LR), and diagnostic odds ratio for the overall
predictive accuracy of IT were computed. RESULTS: Nine studies (21 070 fetuses)
were included in the analysis. IT was successfully assessed in the majority of
fetuses 97.8% (95% CI 97.6-98.0). The diagnostic performance of IT in detecting
SB was as follows: sensitivity: 53.5% (95% CI 42.4-64.3), specificity: 99.7% (95%
CI 99.6-99.8), positive LR: 62.1 (95% CI 12.2-317), negative LR:0.55 (95% CI 0.45
0.68), and diagnostic odds ratio: 223 (95% CI 25-2039). CONCLUSIONS: Intracranial
translucency had low diagnostic accuracy in prediction of open spina bifida, thus
questioning its role as a screening marker for open SB in an unselected
population. When looking at the individual study data, it appears that IT
assessment for open SB prediction can be affected by a high rate of false
positive results potentially leading to unnecessary parental anxiety. (c) 2016
John Wiley & Sons, Ltd.
PMID- 27500986
TI - Normative reference values for the 20 m shuttle-run test in a population-based
sample of school-aged youth in Bogota, Colombia: the FUPRECOL study.
AB - OBJECTIVES: Our aim was to determine the normative reference values of
cardiorespiratory fitness (CRF) and to establish the proportion of subjects with
low CRF suggestive of future cardio-metabolic risk. METHODS: A total of 7244
children and adolescents attending public schools in Bogota, Colombia (55.7%
girls; age range of 9-17.9 years) participated in this study. We expressed CRF
performance as the nearest stage (minute) completed and the estimated peak oxygen
consumption (VO2peak ). Smoothed percentile curves were calculated. In addition,
we present the prevalence of low CRF after applying a correction factor to
account for the impact of Bogota's altitude (2625 m over sea level) on CRF
assessment, and we calculated the number of participants who fell below health
related FITNESSGRAM cut-points for low CRF. RESULTS: Shuttles and VO2peak were
higher in boys than in girls in all age groups. In boys, there were higher levels
of performance with increasing age, with most gains between the ages of 13 and
17. The proportion of subjects with a low CRF, suggestive of future cardio
metabolic risk (health risk FITNESSGRAM category) was 31.5% (28.2% for boys and
34.1% for girls; X2 P = .001). After applying a 1.11 altitude correction factor,
the overall prevalence of low CRF was 11.5% (9.6% for boys and 13.1% for girls;
X2 P = .001). CONCLUSIONS: Our results provide sex- and age-specific normative
reference standards for the 20 m shuttle-run test and estimated VO2peak values in
a large, population-based sample of schoolchildren from a large Latin-American
city at high altitude.
PMID- 27500987
TI - Extensive Necrotic Purpura in Levamisole-Adulterated Cocaine Abuse - A Case
Report.
AB - Levamisole, which is used as an adulterated compound of cocaine, is currently
being seen year after year in cocaine intoxication. For a few cases in the last
decade, necrotic purpura and neutropenia after levamisole/cocaine intoxication
have been described in the medical community. Herein, we present an original case
of levamisole intoxication of a 40-year-old woman who smoked heroin and cocaine
few during a month. She rapidly presented an extensive necrotic purpura of the
nose, cheeks and extremities (lower and upper), and immunologic reactions
(positive anti-MPO and anti-HNE). Levamisole was detected on hairs with ultra
high performance liquid chromatography and tandem mass spectrometry. The case
reports also a probable cocaine supplier deceit, which bring pure drug for
hospital investigation after the intoxication of his client. The intoxicated
woman had survived with several skin and chronic pain complications. That case
recalls the knowledge about levamisole with a short review of the forensic
literature.
PMID- 27500988
TI - Detection of RNA-binding Proteins by In Vitro RNA Pull-down in Adipocyte Culture.
AB - RNA-binding proteins (RBPs) are emerging as a regulatory layer in the development
and function of adipose. RBPs play a key role in the gene expression regulation
at posttranscriptional levels by affecting the stability and translational
efficiency of target mRNAs. RNA pull-down technique has been widely used to study
RNA-protein interaction, which is necessary to elucidate the mechanism underlying
RBPs' as well as long non-coding RNAs' (lncRNAs) function. However, the high
lipid abundance in adipocytes poses a technical challenge in conducting this
experiment. Here a detailed RNA pull-down protocol is optimized for primary
adipocyte culture. An RNA fragment from androgen receptor's (AR) 3' untranslated
region (3'UTR) containing an adenylate-uridylate-rich elementwas used as an
example to demonstrate how to retrieve its RBP partner, HuR protein, from
adipocyte lystate. The method described here can be applied to detect the
interactions between RBPs and noncoding RNAs, as well as between RBPs and coding
RNAs.
PMID- 27500990
TI - Influence of Age and Pathology on Achilles Tendon Properties During a Single-leg
Jump.
AB - Prevalence of Achilles tendinopathy increases with age leading to a weaker tendon
with predisposition to rupture. Conclusive evidence of the influence of age and
pathology on Achilles tendon (AT) properties remains limited, as previous studies
are based on standardized isometric conditions. The study investigates the
influence of age and pathology on AT properties during single-leg vertical jump
(SLVJ). 10 children (C), 10 asymptomatic adults (A), and 10 tendinopathic
patients (T) were included. AT elongation [mm] from rest to maximal displacement
during a SLVJ on a force-plate was sonographically assessed. AT compliance
[mm/N]) and strain [%] was calculated by dividing elongation by peak ground
reaction force [N] and length, respectively. One-way ANOVA followed by Bonferroni
post-hoc correction (alpha=0.05) were used to compare C with A and A with T. AT
elongation (p=0.004), compliance (p=0.001), and strain were found to be
statistically significant higher in C (27+/-3 mm, 0.026+/-0.006 [mm/N], 13+/-2%)
compared to A (21+/-4 mm, 0.017+/-0.005 [mm/N], 10+/-2%). No statistically
significant differences (p>=0.05) was found between A and T (25+/-5 mm, 0.019+/
0.004 [mm/N], 12+/-3%). During SLVJ, tendon responded differently in regards to
age and pathology with children having the most compliant AT. Higher compliance
found in healthy tendons might be considered as a protective factor against load
related injuries.
PMID- 27500989
TI - Regorafenib induced severe toxic hepatitis: characterization and discussion.
AB - BACKGROUND: Regorafenib is the first small-molecule multikinase inhibitor which
showed survival benefits in pretreated metastatic colorectal cancer (mCRC)
patients. Besides classical adverse events of this drug class, hepatotoxicity has
been described as a frequent side effect. MATERIAL AND METHODS: Patients with
refractory mCRC treated with regorafenib in our institution were reviewed. Severe
treatment-related liver toxicity was investigated. Clinical history, liver
histology and genetic assessment (sequence analysis) of cytochrome P3A4 (CYP3A4)
and uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) involved in
regorafenib metabolization were here reported for patients with severe
hepatotoxicity. RESULTS: Among the 93 reviewed patients, 3 presented severe and
icteric toxic hepatitis which was fatal for 1 patient. Histopathological liver
lesions were different depending on the onset of hepatotoxicity (acute or
subacute): acinar zone 3 necrosis in case of acute symptoms, and portal tract
inflammation with porto-central bridging and fibrosis in the delayed
presentation. None of the patients had CYP3A4 gene mutations. Similar
polymorphisms in UGT1A9 gene promoter region (UGT1A9 variant -118T9>10
[rs3832043]) were found in both patients who presented acute hepatitis. Moreover,
it appears retrospectively that both of them already experienced significant
toxicity under irinotecan-based chemotherapy. CONCLUSION: This is the first
report of severe hepatotoxicity with available liver histology and genetic
assessment of enzymes involved in regorafenib metabolization. This report also
reminds the importance of close liver tests monitoring during regorafenib
treatment.
PMID- 27500991
TI - A Model of First-responder Coping: An Approach/Avoidance Bifurcation.
AB - The work of first responders is fraught with numerous stressors, ranging from
potentially traumatic critical incidents to institutional strains. The severity
and pervasiveness of these difficulties prompt a necessary consideration of the
coping methods employed by first responders. The present study developed an
empirical model of first-responder coping strategies, based upon a nationally
representative survey sample of 6240 first responders. Participants were drawn
from Swedish first responders in the following occupations: coast guard, customs
control, military, emergency medical services, fire department and police
services. In the final model, exposure to stress related to well-being through
several indirect paths that in sum accounted for the original direct relationship
between these constructs. These several indirect paths were classified
theoretically as either approach or avoidance coping behaviours or subsequent
health outcomes. In general, approach coping behaviours were related to better
well-being; and avoidance was related to a decrease in the outcome. The size of
the present sample, as well as the diverse nature of the included first
responders, suggests that the resulting model may offer a unique insight into
potentially adaptive pathways for first-responder coping. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27500992
TI - Illusory conjunctions in visual short-term memory: Individual differences in
corpus callosum connectivity and splitting attention between the two hemifields.
AB - Overloading the capacity of visual attention can result in mistakenly combining
the various features of an object, that is, illusory conjunctions. We hypothesize
that if the two hemispheres separately process visual information by splitting
attention, connectivity of corpus callosum-a brain structure integrating the two
hemispheres-would predict the degree of illusory conjunctions. In the current
study, we assessed two types of illusory conjunctions using a memory-scanning
paradigm; the features were either presented across the two opposite hemifields
or within the same hemifield. Four objects, each with two visual features, were
briefly presented together followed by a probe-recognition and a confidence
rating for the recognition accuracy. MRI scans were also obtained. Results
indicated that successful recollection during probe recognition was better for
across hemifields conjunctions compared to within hemifield conjunctions, lending
support to the bilateral advantage of the two hemispheres in visual short-term
memory. Age-related differences regarding the underlying mechanisms of the
bilateral advantage indicated greater reliance on recollection-based processing
in young and on familiarity-based processing in old. Moreover, the integrity of
the posterior corpus callosum was more predictive of opposite hemifield illusory
conjunctions compared to within hemifield illusory conjunctions, even after
controlling for age. That is, individuals with lesser posterior corpus callosum
connectivity had better recognition for objects when their features were
recombined from the opposite hemifields than from the same hemifield. This study
is the first to investigate the role of the corpus callosum in splitting
attention between versus within hemifields.
PMID- 27500993
TI - Rupatadine: global safety evaluation in allergic rhinitis and urticaria.
AB - INTRODUCTION: Rupatadine is a second-generation H1-antihistamine with dual
affinity for histamine H1 and PAF receptors. Rupatadine is indicated for the
treatment of allergic rhinitis and urticaria. AREAS COVERED: A Medline search was
conducted to identify preclinical and clinical studies of rupatadine. This was
supplemented with additional articles obtained from online sources. The focus of
this review is on the safety profile of rupatadine. EXPERT OPINION: The review of
these data indicates that rupatadine is highly selective for histamine H1
receptors, exhibits additional PAF antagonism in in vitro and in vivo studies,
does not cross the blood-brain barrier, and has similar adverse events comparable
with other second-generation antihistamines. Rupatadine is a safe and well
tolerated drug in patients over 2 years old, with no central nervous system or
cardiovascular effects and it can be taken with or without foods.
PMID- 27500995
TI - New Onset of Chronic Diseases and Changes in Lifestyle Risk Factors Among Gulf
War Veterans: A Longitudinal Comparison of High and Low Symptom Reporters.
AB - OBJECTIVE: The aim of this study was to compare new chronic diseases onset and
longitudinal changes in lifestyle risk factors between Gulf War veterans with
different symptom reporting. METHODS: Data were collected from Gulf War veterans
over two periods, and participants were grouped according to baseline symptom
reporting. Logistic, nominal, and ordinal regressions were used for between-group
comparisons. RESULTS: The veterans comprised low, moderate, and high symptom
reporters. New onset of sleep apnea [odds ratio (OR) = 9.49; 95% confidence
interval (CI) = 3.48 to 25.86], musculoskeletal (OR = 8.70; 95% CI = 4.17 to
18.17), psychological (OR = 5.36; 95% CI = 2.46 to 11.70), and cardiovascular (OR
= 3.86; 95% CI = 1.33 to 11.23) conditions was elevated in high versus low
symptom reporters. Although odds of obesity and alcohol use increased over time
and smoking halved, the changes were similar across groups. CONCLUSIONS: These
findings show increasing obesity and alcohol use, and indicate that high
symptomatology among veterans may predict future disease onset.
PMID- 27500994
TI - Shoulder arthritis secondary to rotator cuff tear: A reproducible murine model
and histopathologic scoring system.
AB - Untreated rotator cuff tears can progress to a distinct form of shoulder
arthritis, and the mechanism of this progression is poorly understood.
Biomechanical, molecular and genetic factors may be at play, and a reliable
animal model is needed to enable further research. The purpose of this study was
to create a reproducible model of posttraumatic shoulder arthritis in the mouse,
and to develop a scoring system for this model to enable future research on
interventions, the role of various gene products, and the development of
therapies to alter the natural course of the disease. Forty-five mice underwent
operative ligation of the rotator cuff tendons and were followed for 45 weeks
following surgery, with free cage activity post-operatively. Mice were sacrificed
at various intervals from 2 to 45 weeks post-injury and histopathologic scoring
was developed and tested by blinded reviewers using both quantitative
computational analysis of coronal sections of the shoulder joint and semi
quantitative grading. The scoring system revealed a progressive, time-dependent
set of tissue changes in the shoulder joint with features similar to human cuff
tear arthropathy including acetabularization of the acromion and femoralization
of the humeral head. This model establishes that osteoarthritis of the shoulder
is distinct from osteoarthritis of the knee or hip, with different stages of
degeneration and unique histopathologic features. Using the novel grading
procedure and quantitative assessments presented here, future research using this
model will enable investigators to test established and novel therapies and
evaluate the role of inflammatory factors and gene products in shoulder
arthritis. This study provides a reproducible mouse model of shoulder arthritis
following isolated injury to the rotator cuff which elucidates characteristics of
cuff tear arthropathy and provides a scoring system and venue for future
research. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals,
Inc. J Orthop Res 35:506-514, 2017.
PMID- 27500996
TI - Socioeconomic Differences in Cause-Specific Disability Retirement in Finland,
1988 to 2009.
AB - OBJECTIVE: The major aim was to study socioeconomic inequalities in disability
retirement due to different diagnostic causes over the period 1988 to 2009.
METHODS: The register data are 11% sample of people aged 30 to 64 years and
living in Finland in 1987 to 2007. Incidence rates were calculated for disability
retirement due to different diseases during the follow-up period 1988 to 2009.
RESULTS: The incidence of disability retirement decreased in each socioeconomic
class from the early 1990s onward. Decreasing absolute socioeconomic inequalities
in disability retirement due to any diagnostic cause and musculoskeletal diseases
were seen in the period 1988 to 2009. Musculoskeletal diseases were the largest
contributor to the overall socioeconomic inequalities in disability retirement
throughout the whole study period. CONCLUSIONS: The contribution of
musculoskeletal diseases to the overall socioeconomic inequalities has been large
during the whole study period.
PMID- 27500999
TI - Recognition, Compensation, and Prevention of Karoshi, or Death due to Overwork.
PMID- 27501000
TI - Musculoskeletal Ultrasound Use Among Occupational Medicine Practitioners at the
American Occupational Health Conference.
PMID- 27501001
TI - Working Hours and Incident Cardiovascular Disease With Special Reference to Sleep
Parameters.
PMID- 27501002
TI - Response to Letter to the Editor.
PMID- 27501003
TI - A Prospective Multicenter Randomized Controlled Study on Interleukin-6 Removal
and Induction by a new Hemodialyzer With Improved Biocompatibility in
Hemodialysis Patients: A Pilot Study.
AB - We compared interleukin-6 (IL-6) removal and induction between conventional
polysulfone (Con) and TORAYLIGHT NV (NV) dialyzers in hemodialysis patients.
Twenty patients on Con with high IL-6 concentrations (2.7-8.5 pg/mL) were
randomized to Con or NV group. Dialyzer performance was determined in NV group
while patients were on Con and after being switched onto NV. Erythropoiesis
stimulating agent (ESA) response index (ERI) was assessed every 4 months for one
year. IL-6 clearance was comparable between Con and NV. IL-6 removal rates were
comparable for the first 1 h, but were higher with NV for the entire session (P =
0.03). Before-to-during-dialysis IL-6 concentration ratios were lower with NV on
the venous side after the session (P = 0.03). During the one-year study,
hemoglobin was lower in Con group than in NV group at month 8 (P = 0.046). ERI
decreased in NV and increased in Con group, with a significant difference between
the groups (P = 0.002). NV and Con are comparable in removing IL-6 and both
induce IL-6. However, the data suggest that NV induces less IL-6, which may
reduce the risk of ESA hyporesponsiveness.
PMID- 27501004
TI - Spatial variation in climate mediates gene flow across an island archipelago.
AB - High levels of gene flow among partially isolated populations can overwhelm
selection and limit local adaptation. This process, known as "gene swamping," can
homogenize genetic diversity among populations and reduce the capacity of a
species to withstand rapid environmental change. We studied brown anole lizards
(Anolis sagrei) distributed across seven islands in The Bahamas. We used
microsatellite markers to estimate gene flow among islands and then examined the
correlation between thermal performance and island temperature. The thermal
optimum for sprint performance was correlated with both mean and maximum island
temperature, whereas performance breadth was not correlated with any measure of
temperature variation. Gene flow between islands decreased as the difference
between mean island temperatures increased, even when those islands were adjacent
to one another. These data suggest that phenotypic variation is the result of
either (1) local genetic adaptation with selection against immigrants maintaining
variation in the thermal optimum, (2) irreversible forms of adaptive plasticity
such that immigrants have reduced fitness, or (3) an interaction between fixed
genetic differences and plasticity. In general, the patterns of gene flow we
observed suggest that local thermal environments represent important ecological
filters that can mediate gene flow on relatively fine geographic scales.
PMID- 27501005
TI - Fast and Simplified Method for High Through-put Isolation of miRNA from Highly
Purified High Density Lipoprotein.
AB - Small non-coding RNAs (miRNAs) have been implicated in a variety of human
diseases including metabolic syndromes. They may be utilized as biomarkers for
diagnosis and prognosis or may serve as targets for drug development,
respectively. Recently it has been shown that miRNAs are carried in lipoproteins,
particularly high density lipoproteins (HDL) and are delivered to recipient cells
for uptake. This raises the possibility that miRNAs play a critical and pivotal
role in cellular and organ function via regulation of gene expression as well as
messenger for cell-cell communications and crosstalk between organs. Current
methods for miRNA isolation from purified HDL are impractical when utilizing
small samples on a large scale. This is largely due to the time consuming and
laborious methods used for lipoprotein isolation. We have developed a simplified
approach to rapidly isolate purified HDL suitable for miRNA analysis from plasma
samples. This method should facilitate investigations into the role of miRNAs in
health and disease and in particular provide new insights into the variety of
biological functions, outside of the reverse cholesterol transport, that have
been ascribed to HDL. Also, the miRNA species which are present in HDL can
provide valuable information of clinical biomarkers for diagnosis of various
diseases.
PMID- 27501006
TI - Dual benefits of renin-angiotensin-aldosterone blockade: lowering the blood
pressure and de-stiffening the arteries.
PMID- 27501007
TI - Antiviral therapy improves overall survival in hepatitis C virus-infected
patients who develop diffuse large B-cell lymphoma.
AB - Chronic Hepatitis C virus (HCV) infection is associated with increased incidence
of non-Hodgkin lymphoma. Several studies have demonstrated regression of indolent
lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV
infected patients with diffuse large B-cell lymphoma (DLBCL) is unclear. We
therefore analyzed AVT's impact on oncologic outcomes of HCV-infected patients
(cases) who developed DLBCL. Cases seen at our institution (June 2004-May 2014)
were matched with uninfected counterparts (controls) and then divided according
to prior AVT consisting of interferon-based regimens. We studied 304 patients (76
cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p
= 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement.
Cases never given AVT had DLBCL more refractory to first-line chemotherapy than
that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more
progressive lymphoma at last examination compared to controls (50% vs. 32%; p =
0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse
5-year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01
5.3]; p = 0.04). Furthermore, AVT improved 5-year OS rates among cases in both
univariate (median [Interquartile range]: 39 [26-56] vs. 16 [6-41] months, p =
0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06-0.69]; p = 0.01). This
study highlights the negative impact of chronic HCV on survival of DLBCL patients
and shows that treatment of HCV infection is associated with a better cancer
response to chemotherapy and improves 5-year OS.
PMID- 27501008
TI - To stop or continue aspirin before aortocoronary bypass operations-do we have
enough evidence to adequately guide us?
PMID- 27501009
TI - Commentary: Alexithymia, not autism, is associated with impaired interoception.
PMID- 27501010
TI - Low-dose hyper-radiosensitivity in human hepatocellular HepG2 cells is associated
with Cdc25C-mediated G2/M cell cycle checkpoint control.
AB - PURPOSE: Although the significance of cell cycle checkpoints in overcoming low
dose hyper-radiosensitivity (HRS) has been proposed, the underlying mechanism of
HRS in human hepatocellular cells remains unclear. Therefore, the aim of this
study was to characterize HRS inhuman hepatocellular HepG2 cells and to explore
the molecular mechanism(s) mediating this response. MATERIALS AND METHODS: HepG2
cells were exposed to various single doses of gamma radiation (from 0 Gy to 4
Gy), and then were assayed at subsequent time-points. Survival curves were then
generated using a linear-quadratic (LQ) equation and a modified induced repair
model (MIRM). The percentage of cells in the G1, G2/M, and S phases of the cell
cycle were also examined using propidium iodide (PI) staining and flow cytometry.
Levels of total cell division cyclin 25C (Cdc25C) and phosphorylated Cdc25C were
examined by Western blotting. RESULTS: Low-dose gamma radiation (<0.3 Gy) induced
HRS in HepG2 cells, while doses of 0.3, 0.5, and 2.0 Gy gamma radiation
significantly arrested HepG2 cells in the G2/M phase. While total Cdc25C levels
remained unchanged after irradiation, levels of phosphorylated Cdc25C markedly
increased 6, 16, and 24 h after treatment with 0.5 or 2.0 Gy radiation, and they
peaked after 16 h. The latter observation is consistent with the G2/M arrest that
was detected following irradiation. CONCLUSIONS: These findings indicate that low
dose HRS in HepG2 cells may be associated with Cdc25C-mediated G2/M cell cycle
checkpoint control.
PMID- 27501011
TI - The Cross-Cultural Dementia Screening (CCD): A new neuropsychological screening
instrument for dementia in elderly immigrants.
AB - OBJECTIVE: Currently, approximately 3.9% of the European population are non-EU
citizens, and a large part of these people are from "non-Western" societies, such
as Turkey and Morocco. For various reasons, the incidence of dementia in this
group is expected to increase. However, cognitive testing is challenging due to
language barriers and low education and/or illiteracy. The newly developed Cross
Cultural Dementia Screening (CCD) can be administered without an interpreter. It
contains three subtests that assess memory, mental speed, and executive function.
We hypothesized the CCD to be a culture-fair test that could discriminate between
demented patients and cognitively healthy controls. METHOD: To test this
hypothesis, 54 patients who had probable dementia were recruited via memory
clinics. Controls (N = 1625) were recruited via their general practitioners. All
patients and controls were aged 55 years and older and of six different self
defined ethnicities (Dutch, Turkish, Moroccan-Arabic, Moroccan-Berber, Surinamese
Creole, and Surinamese-Hindustani). Exclusion criteria included current or
previous conditions that affect cognitive functioning. RESULTS: There were
performance differences between the ethnic groups, but these disappeared after
correcting for age and education differences between the groups, which supports
our central hypothesis that the CCD is a culture-fair test. Receiver-operating
characteristic (ROC) and logistic regression analyses showed that the CCD has
high predictive validity for dementia (sensitivity: 85%; specificity: 89%).
DISCUSSION: The CCD is a sensitive and culture-fair neuropsychological instrument
for dementia screening in low-educated immigrant populations.
PMID- 27501012
TI - Nanoindentation and finite element modelling of chitosan-alginate multilayer
coated hydrogels.
AB - Composite soft materials are used as compounds for determining the effects of
mechanical cues on cell behavior and cell encapsulation and for controlling drug
release. The appropriate composite soft materials are conventionally prepared by
selective deposition of polymers at the surface of an ionic hydrogel. In the
present study we address the impact of a mechanically stratified two-layer
structure of these materials on their overall mechanical characterization by
applying a combination of nanoindentation, confocal microscopy and finite element
modelling. We prepare covalent cross-linked hydrogels based on acrylamide (AAM)
and including an anionic group, and impregnate them using a multilayer deposition
strategy of alternating exposure to cationic chitosan and anionic alginate. The
thickness of the chitosan-alginate layer on the hydrogels was determined to be
0.4 +/- 0.05 MUm for 4 bilayers, and 0.7 +/- 0.1 MUm for the 8 bilayer deposition
procedure employing a fluorescently labelled chitosan and confocal microscopy.
The force-indentation data for the AAM gels were highly reproducible, whereas 77%
and 50% of the force-indentation data were reproducible following the 4 and 8
bilayer deposition. The main trends in the reproducible force-distance data were
found to yield an apparent increased Young's modulus after the deposition. Finite
element modelling showed that adaption of a homogeneous Young's modulus for the
specimens with deposited layers yields approximately three times too low
stiffness compared to the estimate of the mechanical properties of the outer part
in the two-layered mechanical model. The thickness of the multilayer region
determined by confocal microscopy was used in the model. This study shows that
the mechanical layered property needs to be included in the interpretation of the
nanoindentation data when there is a significant mechanical contrast.
PMID- 27501014
TI - Internal Morphology-Controllable Self-Assembly in Poly(Ionic Liquid)
Nanoparticles.
AB - Precise control of the interior and outer shapes of polymer nanoparticles has
found broad interest in nanosciences, for example, in fundamental studies of
their physical properties, colloidal behavior, and corresponding applications.
Realizing such control below the 50 nm scale (i.e., a size scale close to
individual polymer chains) requires accurate manipulation of polymerization
techniques and a judicious choice of the chemical structure in monomers and/or
polymers. Here, we constructed a series of well-defined sub-50 nm homopolymer
nanoparticles with controllable shape and highly ordered, complex internal
structures with sub-5 nm domain spacings, starting from 1-vinyl-1,2,4-triazolium
type ionic liquids in a one-pot dispersion polymerization. With cryogenic
electron microscopy and tomography, a morphological evolution of particle shape
and interior at this extremely small size end, unusual for polymer colloids, was
identified and investigated in detail.
PMID- 27501013
TI - A candidate transacting modulator of fetal hemoglobin gene expression in the Arab
Indian haplotype of sickle cell anemia.
AB - Fetal hemoglobin (HbF) levels are higher in the Arab-Indian (AI) beta-globin gene
haplotype of sickle cell anemia compared with African-origin haplotypes. To study
genetic elements that effect HbF expression in the AI haplotype we completed
whole genome sequencing in 14 Saudi AI haplotype sickle hemoglobin homozygotes
seven selected for low HbF (8.2% +/- 1.3%) and seven selected for high HbF (23.5%
+/- 2.6%). An intronic single nucleotide polymorphism (SNP) in ANTXR1, an anthrax
toxin receptor (chromosome 2p13), was associated with HbF. These results were
replicated in two independent Saudi AI haplotype cohorts of 120 and 139 patients,
but not in 76 Saudi Benin haplotype, 894 African origin haplotype and 44 AI
haplotype patients of Indian origin, suggesting that this association is
effective only in the Saudi AI haplotype background. ANTXR1 variants explained
10% of the HbF variability compared with 8% for BCL11A. These two genes had
independent, additive effects on HbF and together explained about 15% of HbF
variability in Saudi AI sickle cell anemia patients. ANTXR1 was expressed at mRNA
and protein levels in erythroid progenitors derived from induced pluripotent stem
cells (iPSCs) and CD34+ cells. As CD34+ cells matured and their HbF decreased
ANTXR1 expression increased; as iPSCs differentiated and their HbF increased,
ANTXR1 expression decreased. Along with elements in cis to the HbF genes, ANTXR1
contributes to the variation in HbF in Saudi AI haplotype sickle cell anemia and
is the first gene in trans to HBB that is associated with HbF only in carriers of
the Saudi AI haplotype. Am. J. Hematol. 91:1118-1122, 2016. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27501015
TI - Pudendal Versus Caudal Block in Children Undergoing Hypospadias Surgery: A
Randomized Controlled Trial.
AB - BACKGROUND AND OBJECTIVES: Postoperative pain management after hypospadias
surgery is often challenging. Caudal block is used for analgesia but has
limitations. This study compares the analgesic efficiency of pudendal block with
that of caudal block in pediatric patients undergoing hypospadias repair surgery.
METHODS: This prospective, double-blind, randomized, controlled study enrolled 84
patients receiving pudendal block or caudal block before hypospadias surgery. In
the pudendal group, the pudendal nerve was identified using a nerve stimulator,
and the block consisted of 0.25% bupivacaine 0.5 mL/kg. In the caudal group, the
caudal block used 0.2% bupivacaine 1 mL/kg. Our primary outcome was pain
intensity within 24 hours postoperatively. The trial was registered at
ClinicalTrials.gov (number: NCT02390388). RESULTS: For the primary outcome,
patients in the pudendal group had lower postoperative pain intensity when
compared with the caudal group (P < 0.001). Three patients in the pudendal group
and all of the patients in the caudal group needed additional analgesia within 24
hours after the surgery (P < 0.001). The family satisfaction rate was
significantly higher in the pudendal group (P < 0.001). CONCLUSIONS: For the
pudendal group, the pain scores for the first 24 hours after the surgery were
significantly lower and the duration of analgesia was longer.
PMID- 27501016
TI - The Erector Spinae Plane Block: A Novel Analgesic Technique in Thoracic
Neuropathic Pain.
AB - Thoracic neuropathic pain is a debilitating condition that is often poorly
responsive to oral and topical pharmacotherapy. The benefit of interventional
nerve block procedures is unclear due to a paucity of evidence and the
invasiveness of the described techniques. In this report, we describe a novel
interfascial plane block, the erector spinae plane (ESP) block, and its
successful application in 2 cases of severe neuropathic pain (the first resulting
from metastatic disease of the ribs, and the second from malunion of multiple rib
fractures). In both cases, the ESP block also produced an extensive
multidermatomal sensory block. Anatomical and radiological investigation in fresh
cadavers indicates that its likely site of action is at the dorsal and ventral
rami of the thoracic spinal nerves. The ESP block holds promise as a simple and
safe technique for thoracic analgesia in both chronic neuropathic pain as well as
acute postsurgical or posttraumatic pain.
PMID- 27501017
TI - Rosacea and gastrointestinal disorders: a population-based cohort study.
AB - BACKGROUND: Rosacea is a common inflammatory facial skin condition. Recent
genetic and epidemiological studies have suggested pathogenic links between
rosacea and gastrointestinal disorders, but data are limited. OBJECTIVES: The
objective was to investigate the association between rosacea and coeliac disease
(CeD), Crohn disease (CD), ulcerative colitis (UC), Helicobacter pylori infection
(HPI), small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome
(IBS), respectively. METHODS: We performed a nationwide cohort study. A total of
49 475 patients with rosacea and 4 312 213 general population controls were
identified using nationwide administrative registers. We established the
prevalence of the aforementioned disorders, and used Cox regression analysis to
obtain hazard ratios (HRs) of the risk of new-onset CeD, CD, UC, HPI, SIBO and
IBS, respectively, in patients with rosacea. RESULTS: The prevalence of CeD, CD,
UC, HPI, SIBO and IBS, respectively, was higher among patients with rosacea when
compared with the control subjects. Adjusted HRs revealed significant
associations between rosacea and CeD (HR 1.46, 1.11-1.93), CD (HR 1.45, 1.19
1.77), UC (HR 1.19, 1.02-1.39), and IBS (HR 1.34, 1.19-1.50), respectively, but
not HPI (HR 1.04, 0.96-1.13) or SIBO (HR 0.71, 0.18-1.86). CONCLUSIONS: Rosacea
is associated with certain gastrointestinal diseases, but the possible pathogenic
link is unknown. Gastrointestinal complaints in patients with rosacea should
warrant clinical suspicion of disease.
PMID- 27501018
TI - MassARRAY determination of somatic oncogenic mutations in solid tumors: Moving
forward to personalized medicine.
AB - This article will review the impact of the recently developed MassARRAY
technology on our understanding of cancer biology and treatment. Analysis of
somatic mutations is a useful tool in selecting personalized therapy, and for
predicting the outcome of many solid tumors. Here, we review the literature on
the application of MassARRAY technology (Sequenom Hamburg, Germany) to determine
the mutation profile of solid tumors from patients. We summarize the use of
commercially available panels of mutations - such as OncoCartaTM or other
combinations - and their concordance with results obtained by using other
technologies, such as next generation sequencing.
PMID- 27501019
TI - Bioluminescence-Based Tumor Quantification Method for Monitoring Tumor
Progression and Treatment Effects in Mouse Lymphoma Models.
AB - Although bioluminescence imaging (BLI) shows promise for monitoring tumor burden
in animal models of cancer, these analyses remain mostly qualitative. Here we
describe a method for bioluminescence imaging to obtain a semi-quantitative
analysis of tumor burden and treatment response. This method is based on the
calculation of a luminoscore, a value that allows comparisons of two animals from
the same or different experiments. Current BLI instruments enable the calculation
of this luminoscore, which relies mainly on the acquisition conditions (back and
front acquisitions) and the drawing of the region of interest (manual markup
around the mouse). Using two previously described mouse lymphoma models based on
cell engraftment, we show that the luminoscore method can serve as a noninvasive
way to verify successful tumor cell inoculation, monitor tumor burden, and
evaluate the effects of in situ cancer treatment (CpG-DNA). Finally, we show that
this method suits different experimental designs. We suggest that this method be
used for early estimates of treatment response in preclinical small-animal
studies.
PMID- 27501020
TI - Quantifying Energy and Water Savings in the U.S. Residential Sector.
AB - Stress on water and energy utilities, including natural resource depletion,
infrastructure deterioration, and growing populations, threatens the ability to
provide reliable and sustainable service. This study presents a demand-side
management decision-making tool to evaluate energy and water efficiency
opportunities at the residential level, including both direct and indirect
consumption. The energy-water nexus accounts for indirect resource consumption,
including water-for-energy and energy-for-water. We examine the relationship
between water and energy in common household appliances and fixtures, comparing
baseline appliances to ENERGY STAR or WaterSense appliances, using a cost
abatement analysis for the average U.S. household, yielding a potential annual
per household savings of 7600 kWh and 39 600 gallons, with most upgrades having
negative abatement cost. We refine the national average cost abatement curves to
understand regional relationships, specifically for the urban environments of Los
Angeles, Chicago, and New York. Cost abatement curves display per unit cost
savings related to overall direct and indirect energy and water efficiency,
allowing utilities, policy makers, and homeowners to consider the relationship
between energy and water when making decisions. Our research fills an important
gap of the energy-water nexus in a residential unit and provides a decision
making tool for policy initiatives.
PMID- 27501021
TI - New definitions for septic shock-a roadmap for a better clinical outcome?
PMID- 27501022
TI - Hemostatic Agents in Spine Surgery: A Critical Analysis Review.
PMID- 27501023
TI - ACL Graft and Contralateral ACL Tear Risk within Ten Years Following
Reconstruction: A Systematic Review.
AB - BACKGROUND: Anterior cruciate ligament (ACL) graft tear and contralateral ACL
injury have devastating effects on patient outcomes following ACL reconstruction.
Long-term results after ACL reconstruction are being reported with greater
frequency, allowing a detailed analysis of the long-term risk of failure.
METHODS: A systematic review of prospective studies that recorded the risk of ACL
graft rupture and contralateral ACL injury following primary ACL reconstruction
was performed. All studies included intra-articular ACL reconstruction with
modern techniques and patellar tendon or hamstring autograft with a minimum
follow-up of ten years. RESULTS: Nine studies met the inclusion and exclusion
criteria. The overall ACL graft rupture risk was 7.9% (211 ruptures in 2682
reconstructions) and ranged from 3.2% to 11.1% in the individual studies. The
overall risk of ACL injury in the contralateral limb was 12.5% (335 injuries in
2682 reconstructions) and ranged from 0.6% to 22.7% in the individual studies.
Among the seven homogeneous studies that were pooled, the overall risk of a
contralateral ACL tear was 1.63 (95% confidence interval [CI]: 1.30 to 2.04)
times that of a graft tear during the follow-up period. CONCLUSIONS: At a minimum
follow-up time of ten years, the risk of contralateral ACL tear significantly
exceeds the risk of ACL graft rupture. Further work is necessary to understand
and potentially reduce this risk of graft and contralateral ACL tears. LEVEL OF
EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete
description of levels of evidence.
PMID- 27501024
TI - Triangular Fibrocartilage Complex: An Anatomic Review.
PMID- 27501025
TI - The Role of Patient Activation in Achieving Better Outcomes and Cost
Effectiveness in Patient Care.
PMID- 27501026
TI - Machine learning for large-scale wearable sensor data in Parkinson's disease:
Concepts, promises, pitfalls, and futures.
AB - For the treatment and monitoring of Parkinson's disease (PD) to be scientific, a
key requirement is that measurement of disease stages and severity is
quantitative, reliable, and repeatable. The last 50 years in PD research have
been dominated by qualitative, subjective ratings obtained by human
interpretation of the presentation of disease signs and symptoms at clinical
visits. More recently, "wearable," sensor-based, quantitative, objective, and
easy-to-use systems for quantifying PD signs for large numbers of participants
over extended durations have been developed. This technology has the potential to
significantly improve both clinical diagnosis and management in PD and the
conduct of clinical studies. However, the large-scale, high-dimensional character
of the data captured by these wearable sensors requires sophisticated signal
processing and machine-learning algorithms to transform it into scientifically
and clinically meaningful information. Such algorithms that "learn" from data
have shown remarkable success in making accurate predictions for complex problems
in which human skill has been required to date, but they are challenging to
evaluate and apply without a basic understanding of the underlying logic on which
they are based. This article contains a nontechnical tutorial review of relevant
machine-learning algorithms, also describing their limitations and how these can
be overcome. It discusses implications of this technology and a practical road
map for realizing the full potential of this technology in PD research and
practice. (c) 2016 International Parkinson and Movement Disorder Society.
PMID- 27501027
TI - HKUST-1 as a Heterogeneous Catalyst for the Synthesis of Vanillin.
AB - Vanillin (4-hydoxy-3-methoxybenzaldehyde) is the main component of the extract of
vanilla bean. The natural vanilla scent is a mixture of approximately 200
different odorant compounds in addition to vanillin. The natural extraction of
vanillin (from the orchid Vanilla planifolia, Vanilla tahitiensis and Vanilla
pompon) represents only 1% of the worldwide production and since this process is
expensive and very long, the rest of the production of vanillin is synthesized.
Many biotechnological approaches can be used for the synthesis of vanillin from
lignin, phenolic stilbenes, isoeugenol, eugenol, guaicol, etc., with the
disadvantage of harming the environment since these processes use strong
oxidizing agents and toxic solvents. Thus, eco-friendly alternatives on the
production of vanillin are very desirable and thus, under current investigation.
Porous coordination polymers (PCPs) are a new class of highly crystalline
materials that recently have been used for catalysis. HKUST-1 (Cu3(BTC)2(H2O)3,
BTC = 1,3,5-benzene-tricarboxylate) is a very well known PCP which has been
extensively studied as a heterogeneous catalyst. Here, we report a synthetic
strategy for the production of vanillin by the oxidation of trans-ferulic acid
using HKUST-1 as a catalyst.
PMID- 27501028
TI - Six-Step Syntheses of (-)-1-Deoxyaltronojirimycin and (+)-1-Deoxymannonojirimycin
from N-Z-O-TBDPS-l-serinal.
AB - Highly stereoselective six-step syntheses of (-)-1-deoxyaltronojirimycin (altro
DNJ) and (+)-1-deoxymannojirimycin (manno-DNJ) from N-Cbz-O-TBDPS-l-serinal are
described. Key transformations involve a two-step preparation of a functionalized
dihydropyridin-3-one as a common intermediate followed by Luche reduction and
dihydroxylation (for altro-DNJ). The same sequence employing an
epoxidation/epoxide opening in place of dihydroxylation furnishes manno-DNJ.
PMID- 27501029
TI - Interleukin (IL) 31 induces in cynomolgus monkeys a rapid and intense itch
response that can be inhibited by an IL-31 neutralizing antibody.
AB - BACKGROUND: Overexpression or administration of interleukin 31 (IL-31) has been
shown to induce a profound itch response in mice and dogs. The chronic pruritus
observed in mouse IL-31 transgenic mice results in the development of skin
lesions and alopecia through excoriation from excessive scratching, a condition
similar to that observed in patients with atopic dermatitis (AD). OBJECTIVE: To
test whether IL-31 induces pruritus in non-human primates and, if so, whether
treatment with an anti-IL-31 neutralizing monoclonal antibody (mAb) can block the
response. METHODS: A series of studies was conducted in cynomolgus monkeys to
evaluate the itch response to recombinant cynomolgus IL-31 (cIL-31)
administration. Three routes of cIL-31 administration (intravenous, intradermal,
and subcutaneous) were evaluated. Subcutaneous treatment with a humanized anti
human IL-31 mAb cross-reactive to cIL-31 was subsequently tested for its ability
to block the response to intradermal cIL-31 administration. RESULTS: Each route
of cIL-31 delivery elicited a scratching response immediately after cIL-31
administration and lasted at least 3 h. Treatment with the IL-31 mAb inhibited
the cIL-31-mediated scratching response in a dose-dependent manner. CONCLUSION:
These results demonstrate that an IL-31 mAb can inhibit IL-31-mediated pruritus
in vivo, and could be an effective therapy for pruritic skin conditions like AD
where IL-31 upregulation may play a role.
PMID- 27501030
TI - Biosorption of methylene blue from wastewater by an extraction residue of Salvia
miltiorrhiza Bge.
AB - Efforts were made in this study to using an extraction residue of Salvia
mitiorrziza Bge (SM), a widely utilized traditional Chinese medicine, as an
effective biosorbent of methylene blue from polluted water. Batch experiments
were carried out with original and chemical modification, particle size, dosage,
solution pH, contact time, and initial concentration of the dye. Experimental
data fit Langmuir isotherm and pseudo-second order kinetic best compared to other
models applied in the study. Characterization of adsorption was determined by FT
IR, SEM and particle surface area measurement. The maximum monolayer biosorption
capacity of raw SM is 100.0mg.g(-1). The citric acid and Na2CO3 modification can
significantly enhance this value up to 161.29 and 178.57mg.g(-1), respectively.
This investigation provides a novel approach for reutilizing the enormous
quantity of Chinese herbal medicine wastes, which is significant since these
dregs have brought out big environmental and heathy problems in the present
China.
PMID- 27501031
TI - Removal of volatile fatty acids and ammonia recovery from unstable anaerobic
digesters with a microbial electrolysis cell.
AB - Continuous assays with a microbial electrolysis cell (MEC) fed with digested pig
slurry were performed to evaluate its stability and robustness to malfunction
periods of an anaerobic digestion (AD) reactor and its feasibility as a strategy
to recover ammonia. When performing punctual pulses of volatile fatty acids (VFA)
in the anode compartment of the MEC, simulating a malfunction of the AD process,
an increase in the current density was produced (up to 14 times, reaching values
of 3500mAm(-2)) as a result of the added chemical oxygen demand (COD), especially
when acetate was used. Furthermore, ammonium diffusion from the anode to the
cathode compartment was enhanced and the removal efficiency achieved up to 60%
during daily basis VFA pulses. An AD-MEC combined system has proven to be a
robust and stable configuration to obtain a high quality effluent, with a lower
organic and ammonium content.
PMID- 27501032
TI - Production of bio-oil rich in acetic acid and phenol from fast pyrolysis of palm
residues using a fluidized bed reactor: Influence of activated carbons.
AB - In this study, palm residues were pyrolyzed in a bench-scale (3kg/h) fast
pyrolysis plant equipped with a fluidized bed reactor and bio-oil separation
system for the production of bio-oil rich in acetic acid and phenol. Pyrolysis
experiments were performed to investigate the effects of reaction temperature and
the types and amounts of activated carbon on the bio-oil composition. The maximum
bio-oil yield obtained was approximately 47wt% at a reaction temperature of 515
degrees C. The main compounds produced from the bio-oils were acetic acid,
hydroxyacetone, phenol, and phenolic compounds such as cresol, xylenol, and
pyrocatechol. When coal-derived activated carbon was applied, the acetic acid and
phenol yields in the bio-oils reached 21 and 19wt%, respectively. Finally, bio
oils rich in acetic acid and phenol could be produced separately by using an in
situ bio-oil separation system and activated carbon as an additive.
PMID- 27501033
TI - Optimization of biohydrogen yield produced by bacterial consortia using residual
glycerin from biodiesel production.
AB - The aims of this study were to simplify the fermentation medium and to optimize
the conditions of dark fermentation of residual glycerin to produce biohydrogen.
It was possible to remove all micronutrients of fermentation medium and improve
biohydrogen production by applying residual glycerin as feedstock. After
statistical analysis of the following parameters pH, glycerin concentration and
volatile suspended solids, the values of 5.5; 0.5g.L(-1) and 8.7g.L(-1),
respectively, were defined as optimum condition for this process. It generated
2.44molH2/molglycerin, an expressive result when compared to previous results
reported in literature and considering that theoretical yield of H2 from glycerol
in dark fermentation process is 3molH2/molglycerol. This study allowed the
improvement of yield and productivity by 68% and 67%, respectively.
PMID- 27501034
TI - Investigation into the lignin decomposition mechanism by analysis of the
pyrolysis product of Pinus radiata.
AB - Lignin pyrolysis chemistry was investigated via the analysis of the products
obtained from the fast pyrolysis of a pine wood at different temperatures.
Methoxy phenols, such as guaiacols and eugenols, were produced mainly at 375 and
475 degrees C, while non-methoxy phenols, such as alkyl phenols and pyrocatechols
were dominant at 525 and 575 degrees C. At 575 degrees C, aromatic hydrocarbons
were formed together with larger amounts of light hydrocarbon gases. When the
temperature was increased from 375 and 475 degrees C, the yield of pyrolytic
lignin was increased, whereas its average molecular weight was decreased. At 525
degrees C, smaller molecular pyrolytic lignin with a maximum concentration of
phenolic hydroxyl groups was produced due to the increased secondary cracking of
the reaction intermediates. On the other hand, at 575 degrees C, larger molecular
pyrolytic lignin with smaller amounts of phenolic hydroxyl groups was produced
due to the increased condensation activity of the pyrolysis reaction
intermediates.
PMID- 27501035
TI - Carbon 13-Metabolic Flux Analysis derived constraint-based metabolic modelling of
Clostridium acetobutylicum in stressed chemostat conditions.
AB - The metabolism of butanol producing bacteria Clostridium acetobutylicum was
studied in chemostat with glucose limited conditions, butanol stimulus, and as a
reference cultivation. COnstraint-Based Reconstruction and Analysis (COBRA) was
applied using additional constraints from (13)C Metabolic Flux Analysis ((13)C
MFA) and experimental measurement results. A model consisting of 451 metabolites
and 604 reactions was utilized in flux balance analysis (FBA). The stringency of
the flux spaces considering different optimization objectives, i.e. growth rate
maximization, ATP maintenance, and NADH/NADPH formation, for flux variance
analysis (FVA) was studied in the different modelled conditions. Also a
previously uncharacterized exopolysaccharide (EPS) produced by C. acetobutylicum
was characterized on monosaccharide level. The major monosaccharide components of
the EPS were 40n-% rhamnose, 34n-% glucose, 13n-% mannose, 10n-% galactose, and
2n-% arabinose. The EPS was studied to have butanol adsorbing property,
70(butanol)mg(EPS)g(-1) at 37 degrees C.
PMID- 27501036
TI - Anchoring and promotion effects of metal oxides on silica supported catalytic
gold nanoparticles.
AB - The understanding of the interactions between the different components of
supported metal doped gold catalysts is of crucial importance for selecting and
designing efficient gold catalysts for reactions such as CO oxidation. To
progress in this direction, a unique supported nano gold catalyst Au/SS was
prepared, and three doped samples (Au/SS@M) were elaborated. The samples before
and after test were characterized by Transmission Electron Microscopy (TEM) and X
ray Photoelectron Spectroscopy (XPS). It is found that the doping metal species
prefer to be located on the surface of gold nanoparticles and that a small amount
of additional reductive metal leads to more efficient reaction. During the
catalytic test, the nano-structure of the metal species transforms depending on
its chemical nature. This study allows one to identify and address the
contribution of each metal on the CO reaction in regard to oxidative species of
gold, silica and dopants. Metal doping leads to different exposure of interface
sites between Au and metal oxide, which is one of the key factors for the change
of the catalytic activity. The metal oxides help the activation of oxygen by two
actions: mobility inside the metal bulk and transfer of water species onto of
gold nanoparticles.
PMID- 27501037
TI - Ligand anchored poly(propyleneimine) dendrimers for brain targeting: Comparative
in vitro and in vivo assessment.
AB - The present investigation was aimed at developing various ligands-anchored
dendrimers and comparing their brain targeting potential at one platform. Sialic
acid (S), glucosamine (G) and concanavalin A (C) anchored poly(propyleneimine)
(PPI) dendritic nanoconjugates were developed and evaluated for delivery of anti
cancer drug, paclitaxel (PTX) to the brain. MTT assay on U373MG human astrocytoma
cells indicated IC50 values of 0.40, 0.65, 0.95, 2.00 and 3.50MUM for PTX loaded
SPPI, GPPI, CPPI, PPI formulations, and free PTX, respectively. The invivo
pharmacokinetics and biodistribution studies in rats showed significantly higher
accumulation of PTX in brain as compared to free PTX. The order of targeting
potential of various ligands under investigation was found as sialic
acid>glucosamine>concanavalin A. Thus, it can be concluded that sialic acid,
glucosamine and Con A can be used as potential ligands to append PPI dendrimers
for enhanced delivery of anticancer drugs to the brain for higher therapeutic
outcome.
PMID- 27501038
TI - 'Chocolate' silver nanoparticles: Synthesis, antibacterial activity and
cytotoxicity.
AB - HYPOTHESIS: Silver nanoparticles (AgNPs) have emerged as a powerful weapon
against antibiotic resistant microorganisms. However, most conventional AgNPs
syntheses require the use of hazardous chemicals and generate toxic organic
waste. Hence, in recent year's, plant derived and biomolecule based synthetics
have has gained much attention. Cacao has been used for years for its medicinal
benefits and contains a powerful reducing agent - oxalic acid. We hypothesized
that, due to the presence of oxalic acid, cacao extract is capable of reducing
silver nitrate (AgNO3) to produce AgNPs. EXPERIMENTS: In this study, AgNPs were
synthesized by using natural cacao extract as a reducing and stabilizing agent.
The reaction temperature, time and reactant molarity were varied to optimize the
synthesis yield. FINDINGS: UV-visible spectroscopy (UV-vis), dynamic light
scattering (DLS) and transmission electron microscopy (TEM) characterization
demonstrated that the synthesized AgNPs were spherical particles ranging in size
from 35 to 42.5nm. The synthesized AgNPs showed significant antibacterial
activity against clinically relevant pathogens such as Escherichia coli,
Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis.
Importantly, these green AgNPs are not cytotoxic to human dermal fibroblasts
(HDFs) at concentrations below 32MUg/ml. We conclude that cacao-based synthesis
is a reproducible and sustainable method for the generation of stable
antimicrobial silver nanoparticles with low cytotoxicity to human cells. The
AgNPs synthesized in this work have promising properties for applications in the
biomedical field.
PMID- 27501039
TI - Immobilization of invertase on chitosan coated gamma-Fe2O3 magnetic nanoparticles
to facilitate magnetic separation.
AB - Industrially important invertase enzyme was immobilized on chitosan coated sol
gel derived gamma-Fe2O3 magnetic nanoparticles (MNPs) to enable it for repetitive
use by magnetic separation. MNPs were characterized by X-ray diffraction (XRD),
dynamic light scattering (DLS), field emission scanning electron microscope (FE
SEM), Fourier transform infrared (FTIR) spectrometer and magnetic measurements.
FTIR studies confirmed successful immobilization of invertase on MNPs. The
ability to convert sucrose into invert syrup was enhanced in immobilized
invertase compared to that of free enzyme. Further it was found that invertase
immobilized on MNPs (IIMNPs) were more stable at varying pH and temperature
conditions. Magnetic separation technique was successfully employed for reuse of
the IIMNPs for 20 times without significant loss of activity.
PMID- 27501040
TI - Novel g-C3N4/Ag2SO4 nanocomposites: Fast microwave-assisted preparation and
enhanced photocatalytic performance towards degradation of organic pollutants
under visible light.
AB - Graphite carbon nitride (g-C3N4)/Ag2SO4 nanocomposites, as highly enhanced
visible-light-driven photocatalysts, were prepared by a fast microwave-assisted
method. The resulting g-C3N4/Ag2SO4 nanocomposites were characterized by X-ray
diffraction, energy dispersive analysis of X-rays, scanning electron microscopy,
transmission electron microscopy, thermogravimetric analysis, Fourier transform
infrared spectroscopy, and ultraviolet-visible diffuse reflectance spectroscopy
techniques. Moreover, charge separation efficiency was studied by
photoluminescence measurements. Photocatalytic activity of the g-C3N4/Ag2SO4
(40%) nanocomposite in degradation of rhodamine B, methylene blue, and fuchsine
is about 6, 3.8, and 3.3-folds greater than that of the g-C3N4 under visible
light illumination. Effect of microwave irradiation time, calcination
temperature, and scavengers of the reactive species on the degradation reaction
was also evaluated. The enhanced photocatalytic activity was mainly ascribed to
the matching band energies of g-C3N4 and Ag2SO4 which leads to an improved
separation of photogenerated electron-hole pairs. Finally, the optimized
nanocomposite was recycled for five times without remarkable decrease of the
photocatalytic activity.
PMID- 27501041
TI - Filamentary superhydrophobic Teflon surfaces: Moderate apparent contact angle but
superior air-retaining properties.
AB - HYPOTHESIS: Micro-scale textured Teflon surfaces, resulting from plasma etching
modification, show extremely high water contact angle values and fairly good
resistance to water penetration when hit by water drops at medium-high speed.
This behavior is more pronounced when these surfaces present denser and smaller
micrometric reliefs. Tailoring the top of these reliefs with a structure which
further stabilizes the air may further increase resistance to wetting (water
penetration) under static and dynamic conditions. EXPERIMENTS: Conditions of the
oxygen fed plasma were tuned in order to explore the possibility of obtaining
differently topped structures on the surface of the polymer. Scanning Electron
Microscopy (SEM) was used to explore topography and X-ray Photoelectron
Spectroscopy (XPS) to assess chemical similarity of the modified surfaces. Beside
the usual advancing and receding water contact angle (WCA) measurements, surfaces
were subjected to high speed impacting drops and immersion in water. FINDINGS: At
milder, i.e. shorter time and lower input power, plasma conditions formation of
peculiar filaments is observed on the top of the sculpted reliefs. Filamentary
topped surfaces result in a lower WCA than the spherical ones, appearing in this
sense less superhydrophobic. However, these surfaces give rise to the formation
of a more pronounced air layer when placed underwater. Further, when hit by water
drops falling at medium/high speed, they show a higher resistance to water
penetration and a sensitively lower surface-liquid contact time. The contact time
is as low as previously observed only on heated solids. This behavior may be
ascribed to the cavities formed beneath the filaments which, similarly with the
salvinia leaf structures, require a surplus of pressure to be filled by water.
Also, it suggests a different concept of superhydrophobicity, which cannot be
expected on the basis of the conventional water contact angle characterization.
PMID- 27501042
TI - Facile synthesis of birnessite-type manganese oxide nanoparticles as
supercapacitor electrode materials.
AB - Manganese oxides are environmentally benign supercapacitor electrode materials
and, in particular, birnessite-type structure shows very promising
electrochemical performance. In this work, nanostructured birnessite was facilely
prepared by adding dropwise NH2OH.HCl to KMnO4 solution under ambient temperature
and pressure. In order to fully exploit the potential of birnessite-type
manganese oxide electrode materials, the effects of specific surface area, pore
size, content of K(+), and manganese average oxidation state (Mn AOS) on their
electrochemical performance were studied. The results showed that with the
increase of NH2OH.HCl, the Mn AOS decreased and the corresponding pore sizes and
specific surface area of birnessite increased. The synthesized nanostructured
birnessite showed the highest specific capacitance of 245Fg(-1) at a current
density of 0.1Ag(-1) within a potential range of 0-0.9V, and excellent cycle
stability with a capacitance retention rate of 92% after 3000 cycles at a current
density of 1.0Ag(-1). The present work implies that specific capacitance is
mainly affected by specific surface area and pore volume, and provides a new
method for the facile preparation of birnessite-type manganese oxide with
excellent capacitive performance.
PMID- 27501043
TI - Phase-field modelling of a miscible system in spinning droplet tensiometer.
AB - The spinning drop tensiometry is used for measurements of surface tension
coefficients, especially, when interfaces are characterised by low and ultra-low
interfacial stresses. A droplet of lighter liquid is introduced into a rotating
capillary that was initially saturated with another heavier liquid. The tube is
subject to axial rotation that results in droplet's elongation along the tube's
axis. The equilibrium shape of the droplet is used to determine the surface
tension coefficient. In this work, the evolution of a slowly miscible droplet
introduced into a spinning capillary is investigated. This technique is
frequently employed for studies of the dynamics of miscible systems, even despite
the fact that a strict equilibrium is never achieved in a mixture of fully
miscible liquids. The numerical modelling of a miscible droplet is fulfilled on
the basis of the phase-field (Cahn-Hilliard) approach. The numerical results are
compared against the experimental data pursuing two objectives: (i) to verify the
use of the phase-field approach as a consistent physics-based approach capable of
accurate tracking of the short- and long-term evolution of miscible systems, and
(ii) to estimate the values of the phenomenological parameters introduced within
the phase-field approach, so making this approach a practical tool for modelling
of thermohydrodynamic changes in miscible systems within various configurations.
PMID- 27501044
TI - Early Differential Diagnosis of Rhino-Orbito-Cerebral Mucormycosis and Bacterial
Orbital Cellulitis: Based on Computed Tomography Findings.
AB - PURPOSE: To identify significant clinical and radiological findings that
distinguish rhino-orbito-cerebral mucormycosis (ROCM) from bacterial orbital
cellulitis (BOC). METHODS: This study was retrospective, multicenter, case
control study that enrolled 34 cases; 14 cases were diagnosed with ROCM and 20
cases were diagnosed with BOC at three different tertiary hospitals between 2005
and 2013. The medical records of all 34 cases were reviewed. The initial clinical
manifestations (eyelid swelling, ptosis, extraocular muscle [EOM] limitation,
conjunctival injection, and chemosis) and computed tomography (CT) findings
(sinus mucosal thickening, full opacification, and air-fluid level) of both
diseases were compared. RESULTS: Patients with diabetes mellitus (DM) and
hypertension (HTN) showed higher incidence rates of ROCM than BOC (DM: p < 0.001,
HTN: p = 0.036). ROCM cases exhibited more frequent EOM limitation than cases
with BOC (100.0% vs. 66.7%, p = 0.024) but less frequent eyelid swelling (35.7%
vs. 90.0%, p = 0.002). However, the incidence rates of ptosis, conjunctival
injection, and chemosis exhibited no differences between the diseases. Abnormal
CT findings were observed in the sinuses of all patients with ROCM, whereas 12
patients with BOC had sinus abnormalities (100.0% vs. 60.0%, p = 0.011).
Thickening of the sinus mucosa was more frequent in patients with ROCM than in
those with BOC (92.9% vs. 45.0%, p = 0.009). No significant differences in full
opacification or air-fluid level were detected between the groups. CONCLUSIONS:
The differential diagnosis of ROCM and BOC is difficult. Nevertheless, physicians
should consider ROCM when a patient with suspected orbital cellulitis presents
with EOM limitation without swollen eyelids or thickening of the sinus mucosa on
a CT scan.
PMID- 27501045
TI - The Genomic Scrapheap Challenge; Extracting Relevant Data from Unmapped Whole
Genome Sequencing Reads, Including Strain Specific Genomic Segments, in Rats.
AB - Unmapped next-generation sequencing reads are typically ignored while they
contain biologically relevant information. We systematically analyzed unmapped
reads from whole genome sequencing of 33 inbred rat strains. High quality reads
were selected and enriched for biologically relevant sequences; similarity-based
analysis revealed clustering similar to previously reported phylogenetic trees.
Our results demonstrate that on average 20% of all unmapped reads harbor
sequences that can be used to improve reference genomes and generate hypotheses
on potential genotype-phenotype relationships. Analysis pipelines would benefit
from incorporating the described methods and reference genomes would benefit from
inclusion of the genomic segments obtained through these efforts.
PMID- 27501046
TI - VM Capacity-Aware Scheduling within Budget Constraints in IaaS Clouds.
AB - Recently, cloud computing has drawn significant attention from both industry and
academia, bringing unprecedented changes to computing and information technology.
The infrastructure-as-a-Service (IaaS) model offers new abilities such as the
elastic provisioning and relinquishing of computing resources in response to
workload fluctuations. However, because the demand for resources dynamically
changes over time, the provisioning of resources in a way that a given budget is
efficiently utilized while maintaining a sufficing performance remains a key
challenge. This paper addresses the problem of task scheduling and resource
provisioning for a set of tasks running on IaaS clouds; it presents novel
provisioning and scheduling algorithms capable of executing tasks within a given
budget, while minimizing the slowdown due to the budget constraint. Our
simulation study demonstrates a substantial reduction up to 70% in the overall
task slowdown rate by the proposed algorithms.
PMID- 27501047
TI - Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of
Freshwater Planaria.
AB - Proteases perform numerous vital functions in flatworms, many of which are likely
to be conserved throughout the phylum Platyhelminthes. Within this phylum are
several parasitic worms that are often poorly characterized due to their complex
life-cycles and lack of responsiveness to genetic manipulation. The flatworm
Schmidtea mediterranea, or planaria, is an ideal model organism to study the
complex role of protein digestion due to its simple life cycle and amenability to
techniques like RNA interference (RNAi). In this study, we were interested in
deconvoluting the digestive protease system that exists in the planarian gut. To
do this, we developed an alcohol-induced regurgitation technique to enrich for
the gut enzymes in S. mediterranea. Using a panel of fluorescent substrates, we
show that this treatment produces a sharp increase in proteolytic activity. These
enzymes have broad yet diverse substrate specificity profiles. Proteomic analysis
of the gut contents revealed the presence of cysteine and metallo-proteases.
However, treatment with class-specific inhibitors showed that aspartyl and
cysteine proteases are responsible for the majority of protein digestion.
Specific RNAi knockdown of the cathepsin B-like cysteine protease (SmedCB)
reduced protein degradation in vivo. Immunohistochemistry and whole-mount in situ
hybridization (WISH) confirmed that the full-length and active forms of SmedCB
are found in secretory cells surrounding the planaria intestinal lumen. Finally,
we show that the knockdown of SmedCB reduces the speed of tissue regeneration.
Defining the roles of proteases in planaria can provide insight to functions of
conserved proteases in parasitic flatworms, potentially uncovering drug targets
in parasites.
PMID- 27501048
TI - Pre-Transplant Cardiovascular Risk Factors Affect Kidney Allograft Survival: A
Multi-Center Study in Korea.
AB - BACKGROUND: Pre-transplant cardiovascular (CV) risk factors affect the
development of CV events even after successful kidney transplantation (KT).
However, the impact of pre-transplant CV risk factors on allograft failure (GF)
has not been reported. METHODS AND FINDINGS: We analyzed the graft outcomes of
2,902 KT recipients who were enrolled in a multi-center cohort from 1997 to 2012.
We calculated the pre-transplant CV risk scores based on the Framingham risk
model using age, gender, total cholesterol level, smoking status, and history of
hypertension. Vascular disease (a composite of ischemic heart disease, peripheral
vascular disease, and cerebrovascular disease) was noted in 6.5% of the patients.
During the median follow-up of 6.4 years, 286 (9.9%) patients had developed GF.
In the multivariable-adjusted Cox proportional hazard model, pre-transplant
vascular disease was associated with an increased risk of GF (HR 2.51; 95% CI
1.66-3.80). The HR for GF (comparing the highest with the lowest tertile
regarding the pre-transplant CV risk scores) was 1.65 (95% CI 1.22-2.23). In the
competing risk model, both pre-transplant vascular disease and CV risk score were
independent risk factors for GF. Moreover, the addition of the CV risk score, the
pre-transplant vascular disease, or both had a better predictability for GF
compared to the traditional GF risk factors. CONCLUSIONS: In conclusion, both
vascular disease and pre-transplant CV risk score were independently associated
with GF in this multi-center study. Pre-transplant CV risk assessments could be
useful in predicting GF in KT recipients.
PMID- 27501049
TI - Migration and epithelial-to-mesenchymal transition of lung cancer can be targeted
via translation initiation factors eIF4E and eIF4GI.
AB - Metastasis underlies cancer morbidity and accounts for disease progression and
significant death rates generally and in non-small cell lung cancer (NSCLC)
particularly. Therefore, it is critically important to understand the molecular
events that regulate metastasis. Accumulating data portray a central role for
protein synthesis, particularly translation initiation (TI) factors eIF4E and
eIF4G in tumorigenesis and patients' survival. We have published that
eIF4E/eIF4GI activities and consequently NSCLC cell migration are modulated by
bone-marrow mesenchymal stem cell secretomes, suggesting a role for TI in
metastasis. Here, we aimed to expand our understanding of the TI factors
significance to NSCLC characteristics, particularly epithelial-to-mesenchymal
transition (EMT) and migration, supportive of metastasis. In a model of NSCLC
cell lines (H1299, H460), we inhibited eIF4E/eIF4GI's expressions (siRNA,
ribavirin) and assessed NSCLC cell lines' migration (scratch), differentiation
(EMT, immunoblotting), and expression of select microRNAs (qPCR). Initially, we
determined an overexpression of several TI factors (eIF4E, eIF4GI, eIF4B, and
DHX29) and their respective targets in NSCLC compared with normal lung samples
(70-350%?, P<0.05). Knockdown (KD) of eIF4E/eIF4GI in NSCLC cell lines (70%?,
P<0.05) also manifested in decreased target levels (ERalpha, SMAD5, NFkB,
CyclinD1, c-MYC, and HIF1alpha) (20-50%?, P<0.05). eIF4E/eIF4GI KD also
attenuated cell migration (60-75%?, P<0.05), EMT promoters (15-90%?, P<0.05), and
enhanced EMT suppressors (30-380%?, P<0.05). The importance of eIF4E KD to NSCLC
phenotype was further corroborated with its inhibitor, ribavirin. Changes in
expression of essential microRNAs implicated in NSCLC cell migration concluded
the study (20-100%, P<0.05). In summary, targeting eIF4E/eIF4GI reduces migration
and EMT, both essential for metastasis, thereby underscoring the potential of TI
targeting in NSCLC therapy, especially the already clinically employed agents
(ribavirin/4EGI). Comparison of these findings with previously reported effects
of eIF4E/eIF4GI KD in multiple myeloma suggests a collective role for these TI
factors in cancer progression.
PMID- 27501050
TI - Ischemic post-conditioning attenuates acute lung injury induced by intestinal
ischemia-reperfusion in mice: role of Nrf2.
AB - Intestinal ischemic post-conditioning (IPo) protects against lung injury induced
by intestinal ischemia-reperfusion (IIR) partly through promotion of expression
and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key
transcription factor that interacts with HO-1 and regulates antioxidant defense.
However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is
not completely understood. Here we show that IPo significantly attenuated IIR
induced lung injury and suppressed oxidative stress and systemic inflammatory
responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently,
the beneficial effects of IPo were abolished by ATRA and Brusatol, potent
inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as
IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays
an important role in the protective effects of IPo against IIR-induced acute lung
injury.
PMID- 27501051
TI - Contrasting Patterns of rDNA Homogenization within the Zygosaccharomyces rouxii
Species Complex.
AB - Arrays of repetitive ribosomal DNA (rDNA) sequences are generally expected to
evolve as a coherent family, where repeats within such a family are more similar
to each other than to orthologs in related species. The continuous homogenization
of repeats within individual genomes is a recombination process termed concerted
evolution. Here, we investigated the extent and the direction of concerted
evolution in 43 yeast strains of the Zygosaccharomyces rouxii species complex (Z.
rouxii, Z. sapae, Z. mellis), by analyzing two portions of the 35S rDNA cistron,
namely the D1/D2 domains at the 5' end of the 26S rRNA gene and the segment
including the internal transcribed spacers (ITS) 1 and 2 (ITS regions). We
demonstrate that intra-genomic rDNA sequence variation is unusually frequent in
this clade and that rDNA arrays in single genomes consist of an intermixing of Z.
rouxii, Z. sapae and Z. mellis-like sequences, putatively evolved by reticulate
evolutionary events that involved repeated hybridization between lineages. The
levels and distribution of sequence polymorphisms vary across rDNA repeats in
different individuals, reflecting four patterns of rDNA evolution: I) rDNA
repeats that are homogeneous within a genome but are chimeras derived from two
parental lineages via recombination: Z. rouxii in the ITS region and Z. sapae in
the D1/D2 region; II) intra-genomic rDNA repeats that retain polymorphisms only
in ITS regions; III) rDNA repeats that vary only in their D1/D2 domains; IV)
heterogeneous rDNA arrays that have both polymorphic ITS and D1/D2 regions. We
argue that an ongoing process of homogenization following allodiplodization or
incomplete lineage sorting gave rise to divergent evolutionary trajectories in
different strains, depending upon temporal, structural and functional
constraints. We discuss the consequences of these findings for Zygosaccharomyces
species delineation and, more in general, for yeast barcoding.
PMID- 27501052
TI - Convergence of visual and whisker responses in the primary somatosensory thalamus
(ventral posterior medial region) of the mouse.
AB - KEY POINTS: Using in vivo electrophysiology, we find that a subset of whisker
responsive neurons in the ventral posterior medial region (VPM) respond to visual
stimuli. These light-responsive neurons in the VPM are particularly sensitive to
optic flow. Presentation of optic flow stimuli modulates the amplitude of
concurrent whisker responses. Visual information reaches the VPM via a circuit
encompassing the visual cortex. These data represent a new example of cross-modal
integration in the primary sensory thalamus. ABSTRACT: Sensory signals reach the
cortex via sense-specific thalamic nuclei. Here we report that neurons in the
primary sensory thalamus of the mouse vibrissal system (the ventral posterior
medial region; VPM) can be excited by visual as well as whisker stimuli. Using
extracellular electrophysiological recordings from anaesthetized mice we first
show that simple light steps can excite a subset of VPM neurons. We then test the
ability of the VPM to respond to spatial patterns and show that many units are
excited by visual motion in a direction-selective manner. Coherent movement of
multiple objects (an artificial recreation of 'optic flow' that would usually
occur during head rotations or body movements) best engages this visual motion
response. We next show that, when co-applied with visual stimuli, the magnitude
of responses to whisker deflections is highest in the presence of optic flow
going in the opposite direction. Importantly, whisker response amplitude is also
modulated by presentation of a movie recreating the mouse's visual experience
during natural exploratory behaviour. We finally present functional and
anatomical data indicating a functional connection (probably multisynaptic) from
the primary visual cortex to VPM. These data provide a rare example of
multisensory integration occurring at the level of the sensory thalamus, and
provide evidence for dynamic regulation of whisker responses according to visual
experience.
PMID- 27501053
TI - Epidemiology and risk factors of uninvestigated dyspepsia, irritable bowel
syndrome, and gastroesophageal reflux disease among students of Damascus
University, Syria.
AB - Uninvestigated dyspepsia (UD), irritable bowel syndrome (IBS), and
gastroesophageal reflux disease (GERD) are common disorders universally. Many
studies have assessed their epidemiological characteristics around the world.
However, such information is not known for Syria. We aim to estimate the
epidemiologic characteristics and possible risk factors for UD, IBS, and GERD
among students at Damascus University, Damascus, Syria. A cross-sectional study
was conducted in July-September 2015 at a campus of Damascus University. A total
of 320 students were randomly asked to complete the survey. We used ROME III
criteria to define UD and IBS, and Montreal definition for GERD. In total, 302
valid participants were included in the analysis. Prevalence for UD, IBS, and
GERD was 25%, 17%, and 16%, respectively. Symptom overlap was present in 46
students (15%), with UD+IBS in 28 (9.3%), UD+GERD in 26 (8.6%), and IBS+GERD in
14 (4.6%) students. Eleven (3.6%) students had symptoms of UD+IBS+GERD. Each of
these overlaps occurred more frequently than expected by chance. Significant risk
factors included cigarettes smoking, waterpipe consumption, and body mass index
<18.5kg/m2 for UD; female gender and three cups of coffee/d for IBS; and two cups
of tea and one to five cigarettes/d for GERD. Risk factors for these disorders
remain poorly characterized and need further investigations.
PMID- 27501054
TI - Lack of genetic variation prevents adaptation at the geographic range margin in a
damselfly.
AB - What limits a species' distribution in the absence of physical barriers? Genetic
load due to asymmetric gene flow and the absence of genetic variation due to lack
of gene flow are hypothesized to constrain adaptation to novel environments in
marginal populations, preventing range expansion. Here, we examined the genetic
structure and geographic variation in morphological traits in two damselflies
(Ischnura asiatica and I. senegalensis) along a latitudinal gradient in Japan,
which is the distribution centre of I. asiatica and the northern limit of I.
senegalensis. Genomewide genetic analyses found a loss of genetic diversity at
the edge of distribution in I. senegalensis but consistently high diversity in I.
asiatica. Gene flow was asymmetric in a south-north direction in both species.
Although body size and wing loading showed decreasing latitudinal clines (smaller
in north) in I. asiatica in Japan, increasing latitudinal clines (larger in
north) in these phenotypic markers were observed in I. senegalensis, particularly
near the northern boundary, which coincided well with the location where genetic
diversity began a sharp decline. In ectothermic animals, increasing latitudinal
cline in these traits was suggested to be established when they failed to adapt
to thermal gradient. Therefore, our findings support the possibility that a lack
of genetic variation rather than geneflow swamping is responsible for the
constraint of adaptation at the margin of geographic distribution.
PMID- 27501055
TI - In vitro study of the antibacterial effect of the bacteriophage T5 thermostable
endolysin on Escherichia coli cells.
AB - AIMS: This study aimed to evaluate lysis of Escherichia coli stationary cell
cultures induced by the combined action of bacteriophage T5 endolysin (l-alanyl-d
glutamate peptidase) and low doses of various cationic agents permeabilizing the
outer membrane of Gram-negative bacteria (polymyxin B, gramicidin D, poly-l
lysine, chlorhexidine and miramistin). METHODS AND RESULTS: The enzyme activity
was assayed with the turbidimetric method. Antimicrobial activity was assessed
through the number of colony-forming units (CFUs); the results of calculation
were represented as logarithmic units. The optical microscopy examination of
bacterial cells was conducted in the phase-contrast mode. The use of
bacteriophage T5 endolysin in combination with polymyxin B (0.4 MUg ml-1 ) or
chlorhexidine (0.5 MUg ml-1 ) made it possible to reduce the number of CFUs by
five orders of magnitude; and in combination with poly-l-lysine (80 MUg ml-1 ) by
four orders, as compared to control. The endolysin was found to be a thermostable
protein: it retained ~65% of its initial activity after heating for 30 min at 90
degrees C. Examining the curves of its thermal denaturation revealed the half
transition temperature to be 56.3 +/- 1.0 degrees C. Circular dichroism spectra
showed that after recooling the protein restored up to 80% of its native
structure. CONCLUSIONS: A substantial synergistic effect of the bacteriophage T5
endolysin and membrane-permeabilizing compounds was demonstrated. SIGNIFICANCE
AND IMPACT OF THE STUDY: The study of thermal stability of the bacteriophage T5
endolysin and the quantified assessment of its antimicrobial activity have been
done for the first time. The approach examined lays foundations for designing a
two-component preparation which would effectively lyse cells of Gram-negative
pathogens from outside.
PMID- 27501056
TI - Digital palpation of the pilot balloon vs. continuous manometry for controlling
the intracuff pressure in laryngeal mask airways.
AB - This study compared two methods of controlling the intracuff pressure in
laryngeal mask airways. One hundred and eighty patients were randomly assigned
into two groups. In the first group (n = 90), after training, the intracuff
pressure was controlled using digital palpation of the pilot balloon. In the
second group (n = 90), continuous manometry was used to control the intracuff
pressure. An upper pressure limit of 60 cmH2 O was set. The median (IQR [range])
intracuff pressure in the palpation group was 130 (125-130 [120-130]) cmH2 O
compared with 29 (20-39 [5-60]) cmH2 O in the manometry group (p < 0.001). In the
palpation group, 37% of patients experienced pharyngolaryngeal complications vs.
12% in the manometry group (p < 0.001). We conclude that the digital palpation
technique is not a suitable alternative to manometry in controlling the intracuff
pressure in laryngeal mask airways.
PMID- 27501057
TI - The mathematics of random mutation and natural selection for multiple
simultaneous selection pressures and the evolution of antimicrobial drug
resistance.
AB - The random mutation and natural selection phenomenon act in a mathematically
predictable behavior, which when understood leads to approaches to reduce and
prevent the failure of the use of these selection pressures when treating
infections and cancers. The underlying principle to impair the random mutation
and natural selection phenomenon is to use combination therapy, which forces the
population to evolve to multiple selection pressures simultaneously that invoke
the multiplication rule of probabilities simultaneously as well. Recently, it has
been seen that combination therapy for the treatment of malaria has failed to
prevent the emergence of drug-resistant variants. Using this empirical example
and the principles of probability theory, the derivation of the equations
describing this treatment failure is carried out. These equations give guidance
as to how to use combination therapy for the treatment of cancers and infectious
diseases and prevent the emergence of drug resistance. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27501058
TI - Biofuel cell operating on activated THP-1 cells: A fuel and substrate study.
AB - It is known that electrochemical energy can be harvested from mammalian cells,
more specifically from white blood cells (WBC). This study focuses on an improved
biofuel cell operating on phorbol myristate acetate (PMA) activated THP-1 human
monocytic cells. Electrochemical investigation showed strong evidence pointing
towards hydrogen peroxide being the primary current source, confirming that the
current originates from NADPH oxidase activity. Moreover, an adequate substrate
for differentiation and activation of THP-1 cells was examined. ITO, gold,
platinum and glass were tested and the amount of superoxide anion produced by
NADPH oxidase was measured by spectrophotometry through WST-1 reduction at 450nm
and used as an indicator of cellular activity and viability. These substrates
were subsequently used in a conventional two-compartment biofuel cell where the
power density output was recorded. The material showing the highest cell activity
compared to the reference cell culture plate and the highest power output was
ITO. Under our experimental conditions, a power density of 4.5MUW/cm2 was
reached. To the best of our knowledge, this is a threefold higher power output
than other leukocyte biofuel cells.
PMID- 27501059
TI - The safety and efficacy of radium-223 dichloride for the treatment of advanced
prostate cancer.
AB - INTRODUCTION: A number of drugs have been shown to extend life expectancy in
castration-resistant prostate cancer (CRPC). Skeletal related events (SREs)
secondary to bone metastases cause significant morbidity for men with CRPC. The
alpha-emitting radiopharmaceutical radium-223 dichloride has been shown to
improve overall survival, time to symptomatic skeletal events (SSEs) and quality
of life in CRPC. AREAS COVERED: The development of radium-223 from pre-clinical
studies to the evidence of efficacy and safety from a phase 3 trial is discussed
as well as its pharmacokinetics and metabolism. The integration of radium-223
into routine care for patients with advanced prostate cancer is included
including a comparison with other agents in this setting. Expert commentary: The
risk/benefit ratio for radium-223 is very similar to that of other agents used in
the CRPC setting and is a treatment option for men unsuitable for cytotoxic
chemotherapy because of comorbidities. The ALSYMPCA trial demonstrated an
improvement in SSEs with radium-223. This is a clinically relevant end-point as
not all radiologically-detected SREs are apparent to patients. The correct
sequencing of the life-prolonging treatments available to men with CRPC is
subject to debate. Radium-223 therapy should be considered before the development
of visceral metastases. Drug-combination studies are underway.
PMID- 27501060
TI - Efficacy and Safety of Bunium Persicum (Boiss) to Inactivate Protoscoleces during
Hydatid Cyst Operations.
AB - BACKGROUND: Current scolicidal agents, which have been used for inactivation of
protoscoleces during surgical procedures, are associated with adverse side
effects including sclerosing cholangitis. This investigation aimed to evaluate
the scolicidal effects of Bunium persicum (Boiss) essential oil against
protoscoleces of hydatid cysts and also its toxicity in a mice model. METHODS:
Protoscoleces were aseptically aspirated from sheep livers having hydatid cysts.
Various concentrations of the essential oil (3.125-50 mcL/mL) were used for 5-30
min. The viability of protoscoleces was confirmed using the eosin exclusion test
(0.1% eosin staining). Further, 48 male NMRI mice were used to determine the
acute and sub-acute toxicity of B. persicum essential oil. RESULTS: The obtained
results revealed that the B. persicum essential oil at the concentrations of 25
and 50 mcL/mL after 5 min of exposure killed 100% protoscoleces. The mean
mortality rate of protoscoleces after 10 min of exposure to the concentration of
12.5 mcL/mL was 100%. Lower concentrations (6.25 and 3.125 mcL/mL) of B. persicum
essential oil, however, indicated a delayed protoscolicidal effects. The LD50
value of intra-peritoneal injection of the B. persicum essential oil was 1.96
mL/kg body wt. No significant difference (p > 0.05) was observed in the clinical
chemistry and hematologic parameters after oral administrations of B. persicum
essential oil at the doses 0.05, 0.1, 0.2, and 4 mL/kg for 14 d. CONCLUSION: Our
findings demonstrated the potent scolicidal activity of B. persicum with no
significant toxicity; it might be used as a natural scolicidal agent in hydatid
cyst surgery.
PMID- 27501061
TI - Synthesis of Protein Bioconjugates via Cysteine-maleimide Chemistry.
AB - The chemical linking or bioconjugation of proteins to fluorescent dyes, drugs,
polymers and other proteins has a broad range of applications, such as the
development of antibody drug conjugates (ADCs) and nanomedicine, fluorescent
microscopy and systems chemistry. For many of these applications, specificity of
the bioconjugation method used is of prime concern. The Michael addition of
maleimides with cysteine(s) on the target proteins is highly selective and
proceeds rapidly under mild conditions, making it one of the most popular methods
for protein bioconjugation. We demonstrate here the modification of the only
surface-accessible cysteine residue on yeast cytochrome c with a ruthenium(II)
bisterpyridine maleimide. The protein bioconjugation is verified by gel
electrophoresis and purified by aqueous-based fast protein liquid chromatography
in 27% yield of isolated protein material. Structural characterization with MALDI
TOF MS and UV-Vis is then used to verify that the bioconjugation is successful.
The protocol shown here is easily applicable to other cysteine - maleimide
coupling of proteins to other proteins, dyes, drugs or polymers.
PMID- 27501062
TI - Long-term anti-endotoxin/E. coli efficacy in mice transfected with AAV2/1-muBPI25
-muFcgamma1.
AB - Bactericidal/permeability increasing (BPI) is an antibiotic protein which kills
Gram-negative bacteria and neutralizes endotoxin. We have previously developed a
recombinant adeno-associated virus which contains human BPI amino acid residues 1
199 and Fc fragment of human IgG1 gene (AAV-hBPI-Fc) and shown that the
recombinant virus can protect mice from lethal endotoxemia. However, whether AAV
hBPI-Fc can be used in vivo for the long term remains unclear. To address this,
we established an adeno-associated virus-containing mouse BPI and Fc fragment
genes (muBPI-Fc) and compared antigenicity of these recombinant proteins in
murine models. Immunohistochemistry showed the expression of both fusion proteins
at injected sites. ELISA and Western blotting showed that the muBPI-Fc protein
was detected in serum up to 8 weeks after injection, without generation of
autoantibodies against muBPI-Fc. In contrast, expressed hBPI-Fc protein was only
detected on the 2nd week, whereas the autoantibody against hBPI-Fc protein
occurred in serum from the 4th week to the end of study. muBPI-Fc also reduced
production of proinflammatory cytokines and protected mice from endotoxemia and
bacteremia. Our data showed that AAV-muBPI-Fc has potential long-term efficacy as
an anti-endotoxin and has anti-bacterial activity in mice, suggesting the
potential clinical application of AAV-hBPI-Fc, such as in endotoxin shock.
PMID- 27501063
TI - "Is voice a marker for Autism spectrum disorder? A systematic review and meta
analysis".
AB - Individuals with Autism Spectrum Disorder (ASD) tend to show distinctive,
atypical acoustic patterns of speech. These behaviors affect social interactions
and social development and could represent a non-invasive marker for ASD. We
systematically reviewed the literature quantifying acoustic patterns in ASD.
Search terms were: (prosody OR intonation OR inflection OR intensity OR pitch OR
fundamental frequency OR speech rate OR voice quality OR acoustic) AND (autis* OR
Asperger). Results were filtered to include only: empirical studies quantifying
acoustic features of vocal production in ASD, with a sample size >2, and the
inclusion of a neurotypical comparison group and/or correlations between acoustic
measures and severity of clinical features. We identified 34 articles, including
30 univariate studies and 15 multivariate machine-learning studies. We performed
meta-analyses of the univariate studies, identifying significant differences in
mean pitch and pitch range between individuals with ASD and comparison
participants (Cohen's d of 0.4-0.5 and discriminatory accuracy of about 61-64%).
The multivariate studies reported higher accuracies than the univariate studies
(63-96%). However, the methods used and the acoustic features investigated were
too diverse for performing meta-analysis. We conclude that multivariate studies
of acoustic patterns are a promising but yet unsystematic avenue for establishing
ASD markers. We outline three recommendations for future studies: open data, open
methods, and theory-driven research. Autism Res 2017, 10: 384-407. (c) 2016
International Society for Autism Research, Wiley Periodicals, Inc.
PMID- 27501065
TI - Night shift work and other determinants of estradiol, testosterone, and
dehydroepiandrosterone sulfate among middle-aged nurses and midwives.
AB - OBJECTIVES: The aims of our study were to (i) investigate the association between
rotating night shift work and blood concentrations of estradiol, testosterone and
dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non
occupational determinants. METHODS: A cross-sectional study was conducted on 345
premenopausal and 187 postmenopausal nurses and midwives (263 women working
rotating night shifts and 269 women working during days). Data from in-person
interviews were used, anthropometric measurements were performed, and body mass
index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine
samples were collected. Multiple linear regression models were fitted with
hormone concentrations as dependent variables, and night shift work
characteristics and demographic, reproductive, lifestyle and anthropometric
determinants as independent variables. Modification of the effect by chronotype
was examined. RESULTS: Among postmenopausal women, we observed a statistically
significant positive association between the total duration of night shift work
>15 years and estradiol level (P<0.05 when compared to night work duration <5
years). Night shift work characteristics were significantly associated with
estradiol among morning-type postmenopausal women. The well-established
associations between hormones and their major determinants, such as age and BMI,
were confirmed. CONCLUSIONS: The findings of our study imply that prolonged night
shift work may be associated with increased estradiol levels among postmenopausal
women, especially among the morning-type postmenopausal women.
PMID- 27501066
TI - Free Energy Contribution Analysis Using Response Kernel Approximation: Insights
into the Acylation Reaction of a Beta-Lactamase.
AB - A widely applicable free energy contribution analysis (FECA) method based on the
quantum mechanical/molecular mechanical (QM/MM) approximation using response
kernel approaches has been proposed to investigate the influences of
environmental residues and/or atoms in the QM region on the free energy profile.
This method can evaluate atomic contributions to the free energy along the
reaction path including polarization effects on the QM region within a
dramatically reduced computational time. The rate-limiting step in the
deactivation of the beta-lactam antibiotic cefalotin (CLS) by beta-lactamase was
studied using this method. The experimentally observed activation barrier was
successfully reproduced by free energy perturbation calculations along the
optimized reaction path that involved activation by the carboxylate moiety in
CLS. It was found that the free energy profile in the QM region was slightly
higher than the isolated energy and that two residues, Lys67 and Lys315, as well
as water molecules deeply influenced the QM atoms associated with the bond
alternation reaction in the acyl-enzyme intermediate. These facts suggested that
the surrounding residues are favorable for the reactant complex and prevent the
intermediate from being too stabilized to proceed to the following deacylation
reaction. We have demonstrated that the free energy contribution analysis should
be a useful method to investigate enzyme catalysis and to facilitate intelligent
molecular design.
PMID- 27501067
TI - Nanoscale Electrochemistry of sp(2) Carbon Materials: From Graphite and Graphene
to Carbon Nanotubes.
AB - Carbon materials have a long history of use as electrodes in electrochemistry,
from (bio)electroanalysis to applications in energy technologies, such as
batteries and fuel cells. With the advent of new forms of nanocarbon,
particularly, carbon nanotubes and graphene, carbon electrode materials have
taken on even greater significance for electrochemical studies, both in their own
right and as components and supports in an array of functional composites. With
the increasing prominence of carbon nanomaterials in electrochemistry comes a
need to critically evaluate the experimental framework from which a microscopic
understanding of electrochemical processes is best developed. This Account
advocates the use of emerging electrochemical imaging techniques and confined
electrochemical cell formats that have considerable potential to reveal major new
perspectives on the intrinsic electrochemical activity of carbon materials, with
unprecedented detail and spatial resolution. These techniques allow particular
features on a surface to be targeted and models of structure-activity to be
developed and tested on a wide range of length scales and time scales. When high
resolution electrochemical imaging data are combined with information from other
microscopy and spectroscopy techniques applied to the same area of an electrode
surface, in a correlative-electrochemical microscopy approach, highly resolved
and unambiguous pictures of electrode activity are revealed that provide new
views of the electrochemical properties of carbon materials. With a focus on
major sp(2) carbon materials, graphite, graphene, and single walled carbon
nanotubes (SWNTs), this Account summarizes recent advances that have changed
understanding of interfacial electrochemistry at carbon electrodes including: (i)
Unequivocal evidence for the high activity of the basal surface of highly
oriented pyrolytic graphite (HOPG), which is at least as active as noble metal
electrodes (e.g., platinum) for outer-sphere redox processes. (ii) Demonstration
of the high activity of basal plane HOPG toward other reactions, with no
requirement for catalysis by step edges or defects, as exemplified by studies of
proton-coupled electron transfer, redox transformations of adsorbed molecules,
surface functionalization via diazonium electrochemistry, and metal
electrodeposition. (iii) Rationalization of the complex interplay of different
factors that determine electrochemistry at graphene, including the source
(mechanical exfoliation from graphite vs chemical vapor deposition), number of
graphene layers, edges, electronic structure, redox couple, and electrode history
effects. (iv) New methodologies that allow nanoscale electrochemistry of 1D
materials (SWNTs) to be related to their electronic characteristics (metallic vs
semiconductor SWNTs), size, and quality, with high resolution imaging revealing
the high activity of SWNT sidewalls and the importance of defects for some
electrocatalytic reactions (e.g., the oxygen reduction reaction). The
experimental approaches highlighted for carbon electrodes are generally
applicable to other electrode materials and set a new framework and course for
the study of electrochemical and interfacial processes.
PMID- 27501068
TI - Atomoxetine ameliorates nocturnal enuresis with subclinical attention
deficit/hyperactivity disorder.
AB - BACKGROUND: Recent studies have shown that incontinence and attention
deficit/hyperactivity disorder (ADHD) coexist and there is an interaction between
them. The treatment for nocturnal enuresis (NE) and ADHD, however, has not been
established. METHODS: At the first visit to the outpatient clinic, physical
examination and history taking were carried out in 265 new patients with NE.
After excluding the possibility of comorbid ADHD and related disorders, patients
with monosymptomatic NE (MNE) were treated with desmopressin and/or alarm, and
those with non-monosymptomatic NE (NMNE) were treated with anti-cholinergics
and/or alarm. This 12 week treatment did not work in 65 patients, and they were
re-assessed for comorbid ADHD. A total of 24 were diagnosed with ADHD, and they
were treated with atomoxetine (1.8 mg/kg/day) in addition to ongoing therapy for
NE. RESULTS: After 8 weeks of atomoxetine, the average wet nights per months was
significantly decreased: 18.5-4.6 in the MNE group (P = 0.001), and 22.1-12.4 in
the NMNE group (P = 0.0251). Overall, atomoxetine was beneficial in 19 of 24
patients. CONCLUSIONS: Atomoxetine may be a suitable option for refractory NE
with comorbid ADHD.
PMID- 27501069
TI - Cytomegalovirus-Induced Hemophagocytic Lymphohistiocytosis in an Extreme Preterm
Infant: Recognition and Therapy Leading to Recovery.
AB - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease that can
be triggered by cytomegalovirus, a relatively common infectious exposure to
neonates. The clinical presentation is common to many acute illnesses seen in
extreme premature infants; however, there are key clinical and laboratory
findings that can lead to the diagnosis. PURPOSE: We present a case of an extreme
premature infant of 25 weeks' gestation who developed cytomegalovirus-induced
HLH. Using the current published protocols that are used in pediatric cancer can
be adapted for use in a premature infant, which led to remission of HLH and
eventual discharge from the neonatal intensive care unit. IMPLICATIONS FOR
PRACTICE: There are published treatment protocols used in pediatric oncology that
when initiated early can lead to favorable outcomes and remission in even the
most fragile neonates. IMPLICATIONS FOR RESEARCH: Additional studies are needed
on the pharmacokinetics, dosing, and side effects on medications used for
treatment of HLH in preterm infants. Additional research is needed to improve the
clinician's ability to reach the diagnosis as well as define treatment strategies
that provide optimal outcomes.
PMID- 27501070
TI - Establishment of the Relationship Between Fathers and Premature Infants in
Neonatal Units.
AB - BACKGROUND: Parents and their preterm infants (born between 32-37 weeks of
gestation) are often overlooked by the healthcare system. And very little
attention is given to the relationship parents develop with their infants in the
neonatal unit (NNU). Specifically, very few studies focused on fathers and how
they establish a relationship with their infants. However, we know that the
father-infant relationship is extremely important for their future social
development and more. PURPOSE: This article presents the results of a qualitative
study of the establishment of the father-premature infant relationship in an NNU.
METHODS/SEARCH STRATEGY: The study's theoretical framework was Bell's model of
the parent-infant relationship, which encompasses discovery, physical proximity,
communication, involvement, and emotional attachment. Ten fathers of premature
infants (gestational age: 32-37 weeks) participated in 2 semistructured
interviews (1 individual and 1 "in situ," ie, at the infant's bedside) during the
first week following the premature birth. FINDINGS/RESULTS: The results confirm
the emergence of different components of the relationship between fathers and
their children from the first days of hospitalization in the NNU. The commitment
component is the basis for the development of other components in the
relationship with their children. Furthermore, involvement influences the
deployment of emotional attachment, discovery, physical proximity, and
communication toward premature infants. Similarly, the 5 themes of the model can
be seen as forming a dynamic nexus in which each theme influences the others.
IMPLICATIONS FOR PRACTICE: For neonatal nurses, this model of the early father
child relationship helps the understanding of the deployment of that relationship
according to 5 components. Similarly, it provides awareness of the experiences of
fathers so that nurses can be better equipped to support and individualize
interventions tailored to their specific needs, thus helping them develop and
sustain the relationship with their children. IMPLICATIONS FOR RESEARCH: This
study allows us to better understand fathers' experience regarding the
establishment of the relationship to their premature infants born between 32 and
37 weeks of gestation. However, there is little understanding about the early
paternal experience and more research on this dyad is necessary in neonatology.
PMID- 27501071
TI - [Distal Pancreatectomy with Autologous Fibrin Sealant - Implementation of an
Established Concept of Tissue Sealing in Pancreatic Surgery].
AB - Background: Postoperative pancreatic fistulas (POPF) remain a major concern after
distal pancreatectomy. Irrespective of the technique to close the pancreatic
remnant, pancreatic fistulas will occur in approximately 30 % of patients
undergoing distal pancreatectomy. For the first time ever, autologous fibrin
sealant (Vivostat(r)) was used to additionally seal the pancreatic remnant after
a distal pancreatectomy. The aim was to analyse whether this changes the
postoperative outcome. Patients/Material and Methods: In 2015, a technical case
series was performed in 15 patients who underwent distal pancreatectomy. The
pancreatic remnant was additionally sealed with autologous fibrin sealant
(Vivostat(r)). Results: A postoperative pancreatic fistula (POPF) occurred in
5/15 patients (33 %). One patient had a POPF grade A (1/15, 6.7 %), whereas a
POPF grade B occurred in 4/15 patients (26.7 %). 75 % (3/4) of the patients with
a POPF grade B were sufficiently treated with antibiotics, whereas a CT-guided
percutaneous drainage had to be placed only in one case. Conclusion: Autologous
fibrin sealant is simple to apply and seems to be well tolerated. However, it
does not seem to avoid the development of postoperative pancreatic fistulas after
distal pancreatectomy.
PMID- 27501072
TI - [Symptoms, Diagnostics, Treatment and Classification of 22 Patients with
Postpancreatectomy Haemorrhage (PPH) in a Series of 400 Consecutive Pancreatic
Head Resections and Pancreatectomies].
AB - Introduction: Postpancreatectomy haemorrhage (PPH) is a dangerous complication
after pancreatic resection. Patients and Methods: From 2006 to 2015, 400
consecutive pancreatic head resections and pancreatectomies were performed and
prospectively documented. This study analysed incidence, treatment and outcome of
patients with PPH. Results: Incidence of PPH was 5.5 % (n = 22). PPH occurred in
a median of eight days after pancreatic surgery with an equal frequency of
symptoms being caused by gastrointestinal bleeding (n = 11) and abdominal
bleeding (n = 11). Postoperative pancreatic fistulas (POPF) were significantly
more frequent in case of PPH (45 % POPF in case of PPH vs. 20 % POPF in case of
no PPH, p < 0.01). PPH was more frequent after pancreatogastrostomy (8/70; 11 %)
than after pancreatojejunostomy (11/281; 4 %; p = 0.01). The majority of
bleedings after pancreatogastrostomy came from the intragastric cut surface of
the pancreas. During the first week, relaparotomy was significantly more frequent
(n = 5; 56 %) than in late PPH (n = 1; 8 %; p = 0.01). In late PPH, interventions
(angiography; n = 7, endoscopy; n = 4) were more frequent. In 16 severe cases,
surgical/interventional bleeding control (n = 12) or relevant transfusions of
more than 3 units of packed red blood cells (n = 4) were performed. Compared with
the whole group, mortality was significantly increased in case of PPH (13.6 % in
case of PPH vs. 3.7 % in case of no PPH; p = 0.03). Conclusion: PPH is an
episodic and potentially life-threatening complication with an increased
mortality rate, which is frequently associated with impaired healing of the
pancreatic anastomosis. Diagnostic investigation and treatment of PPH requires an
experienced surgical centre with a close cooperation with endoscopy and
(interventional) radiology.
PMID- 27501073
TI - [Prophylaxis of Recurrent Venous Leg Ulcer].
AB - Venous leg ulcer (VLU) counts among the most common chronic wounds in Europe.
Treatment is lengthy, cumbersome and costly, and there is a high rate of
recurrence. This review shows the measures that should be offered to every
patient with healed VLU to permanently prevent recurrence. To prevent VLU in case
of varicose veins, the progression of chronic venous insufficiency (CVI) has to
be stopped. There is convincing evidence that the effective treatment of varicose
veins reduces the recurrence rate in patients with VLU. In patients with post
thrombotic syndrome (PTS), further thrombosis should be prevented through
targeted prophylaxis of new thromboembolic events. The benefit of endovascular
revascularization on the VLU recurrence rate in patients with post-thrombotic
damage in the pelvic veins has not been proven in clinical studies. On the other
hand, it has been clearly demonstrated in several studies that compression
therapy is the basic procedure for the prevention of recurrent VLU in patients
with varicose veins or PTS, regardless of whether other measures have been
implemented or not. Good adherence in patients with compression therapy is more
important than choosing the highest possible compression class. Future efforts
for patients with VLU must aim to provide therapists with tools and treatment
strategies to guide their patients and to increase patients' acceptance and
understanding of the importance of self-management, in particular regarding
compression therapy for the prevention of recurrent VLU.
PMID- 27501074
TI - Purification of Native Complexes for Structural Study Using a Tandem Affinity Tag
Method.
AB - Affinity purification approaches have been successful in isolating native
complexes for proteomic characterization. Structural heterogeneity and a degree
of compositional heterogeneity of a complex do not usually impede progress in
conducting such studies. In contrast, a complex intended for structural
characterization should be purified in a state that is both compositionally and
structurally homogeneous as well as at a higher concentration than required for
proteomics. Recently, there have been significant advances in the application of
electron microscopy for structure determination of large macromolecular
complexes. This has heightened interest in approaches to purify native complexes
of sufficient quality and quantity for structural determination by electron
microscopy. The Tandem Affinity Purification (TAP) method has been optimized to
extract and purify an 18-subunit, ~ 0.8 MDa ribonucleoprotein assembly from
budding yeast (Saccharomyces cerevisiae) suitable for negative stain and electron
cryo microscopy. Herein is detailed the modifications made to the TAP method, the
rationale for making these changes, and the approaches taken to assay for a
compositionally and structurally homogeneous complex.
PMID- 27501075
TI - Systematic evaluation of circulating inflammatory markers for hepatocellular
carcinoma.
AB - BACKGROUNDS & AIMS: A number of circulating inflammatory factors are implicated
in the pathogenesis and prognostication of hepatocellular carcinoma (HCC). We aim
to evaluate the prognostication of multiple serum inflammatory factors
simultaneously and develop an objective inflammatory score for HCC. METHODS: A
prospective cohort of 555 patients with HCC with paired serum samples was accrued
from 2009 to 2012. The blood levels of conventional inflammatory markers, namely
C-reactive protein (CRP), albumin, neutrophils, lymphocytes and platelet, were
determined, and 41 other exploratory markers were measured by a multiplex assay.
The prognostication and interaction of markers were determined by univariate and
multivarite analyses. RESULTS: The cohort was randomly divided into training
cohort (n=139) and validation cohort (n=416). There were no differences in
baseline characteristics between the two cohorts. In the training cohort,
independent prognostic factors for overall survival included CRP (hazard ratio
[HR] 1.107; P=.003), albumin (HR 0.953; P=.032) and interleukin-8 (HR=5.816;
P<.001). We have modified the existing inflammation-based index (IBI) by adding
serum interleukin-8 level. The modified IBI could stratify patients into four
groups with distinct overall survival (P<.001). The results were also validated
in the validation cohort. When compared with IBI and other conventional
inflammatory markers, the modified IBI had better prognostic performance with
higher c-index and homogeneity likelihood ratio chi-square. CONCLUSIONS: Among
the conventional and exploratory circulating inflammatory markers, higher CRP,
lower albumin and higher interleukin-8 were independent prognosticators. By
combining these factors, a simple and accurate inflammatory index could be
constructed.
PMID- 27501076
TI - Beyond Taphonomy: Exploring Craniometric Variation Among Anatomical Material.
AB - Anatomical crania are occasionally encountered in forensic anthropology
laboratories when that material is mistaken for forensically significant human
remains. Using craniometric analyses and statistical measures of sample
homogeneity, we determine whether anatomical material can be described as a
single, homogenous group or as a diverse mix of populations. Twenty-one
interlandmark distances were collected from 85 anatomical preparations. Distance
measures were calculated between all pairs using a pooled within-sample
variance/covariance matrix and then subjected to a Defrise-Gussenhoven test
between each paired distance to test whether each pair was drawn randomly from
the same population. In the Defrise-Gussenhoven analysis, twenty-two percent (n =
66) of the 300 pairwise combinations were significant at the 0.05 level or below.
The level of homogeneity suggests a majority of that material originated from the
subcontinent of India or West Asia. Therefore, anatomical material can be viewed
as a moderately homogenous group, but with a shared taphonomic history.
PMID- 27501077
TI - Tactile massage as a nursing intervention in child and adolescent psychiatry:
nurses' experiences.
AB - : WHAT IS KNOWN ABOUT THE SUBJECT?: There is little research on the
implementation of tactile massage in child and adolescent psychiatry that
describes children's and adolescents' experiences and outcomes. There is also
limited knowledge of providing tactile massage in child and adolescent
psychiatry. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: This paper describes
10 nurses' experiences of tactile massage as a nursing intervention in child and
adolescent psychiatry. The nurses considered tactile massage a non-verbal nursing
intervention that could complement other available treatments. It reveals their
reflections on the impact of tactile massage on their nursing and on themselves
as a person, including the belief that they had developed deepened self
reflection and attentiveness. The nurses highlighted the importance of providing
a trusting environment and collaborating with the children and adolescents. They
both experienced and observed that tactile massage triggered various physical and
mental processes in the children and adolescents, such as improvement in sleep
disturbances, an ability to relax in body and mind and a deeper connectedness
with their own bodies and feelings. The nurses described instructing next of kin
in the use of tactile massage, which they believed could serve as a tool at home,
mainly as a way for next of kin to help their children to relax, fall asleep more
easily and to deepen connectedness. However, the nurses stressed the need to
consider if it was appropriate or desired by the children and adolescents. WHAT
ARE THE IMPLICATIONS FOR PRACTICE?: Tactile massage addresses the individual's
emotional and physiological responses and could therefore bring holistic nursing
to child and adolescent psychiatry. It could also help nurses in child and
adolescent psychiatry to develop their attentiveness and sensitivity in
acknowledging the needs of children and adolescents in psychiatric care.
ABSTRACT: Introduction There is limited research on tactile massage in child and
adolescent psychiatry and no studies investigating experiences of providing
tactile massage in child and adolescent psychiatry were found. Aim The aim was
therefore to describe nurses' experiences of providing tactile massage as a
nursing intervention in child and adolescent psychiatry. Method Ten nurses
trained in tactile massage and employed at five different child and adolescent
psychiatry clinics in Sweden participated in a qualitative study. Semi-structured
interviews were conducted, transcribed verbatim and analysed by qualitative
content analysis. Results Three categories emerged from the analysis. 'Confirming
body and mind', 'Building a trusting relationship' and 'Instructing next of kin
in tactile massage'. Attentiveness to and respect for the integrity of the
children and adolescents were essential for creating a trusting relationship with
them. Tactile massage was found to trigger various physical and mental processes
in the children and adolescents. The nurses reflected on the impact of tactile
massage on their nursing and on themselves as a person, stating that it had led
to the development of self-reflection and attentiveness. Implications for
practice Tactile massage addresses the individual's emotional and physiological
responses and could therefore bring holistic nursing to child and adolescent
psychiatry. It might also enhance attentiveness and sensitivity on the part of
child and adolescent psychiatry nurses when acknowledging the needs of children
and adolescents in psychiatric care.
PMID- 27501080
TI - Evaluating an Organizational-Level Occupational Health Intervention in a Combined
Regression Discontinuity and Randomized Control Design.
AB - Organizational-level occupational health interventions have great potential to
improve employees' health and well-being. However, they often compare
unfavourably to individual-level interventions. This calls for improving methods
for designing, implementing and evaluating organizational interventions. This
paper presents and discusses the regression discontinuity design because, like
the randomized control trial, it is a strong summative experimental design, but
it typically fits organizational-level interventions better. The paper explores
advantages and disadvantages of a regression discontinuity design with an
embedded randomized control trial. It provides an example from an intervention
study focusing on reducing sickness absence in 196 preschools. The paper
demonstrates that such a design fits the organizational context, because it
allows management to focus on organizations or workgroups with the most salient
problems. In addition, organizations may accept an embedded randomized design
because the organizations or groups with most salient needs receive obligatory
treatment as part of the regression discontinuity design. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27501079
TI - Applying Fluorescence Resonance Energy Transfer (FRET) to Examine Effector
Translocation Efficiency by Coxiella burnetii during siRNA Silencing.
AB - Coxiella burnetii, the causative agent of Q fever, is an intracellular pathogen
that relies on a Type IV Dot/Icm Secretion System to establish a replicative
niche. A cohort of effectors are translocated through this system into the host
cell to manipulate host processes and allow the establishment of a unique
lysosome-derived vacuole for replication. The method presented here involves the
combination of two well-established techniques: specific gene silencing using
siRNA and measurement of effector translocation using a FRET-based substrate that
relies on beta-lactamase activity. Applying these two approaches, we can begin to
understand the role of host factors in bacterial secretion system function and
effector translocation. In this study we examined the role of Rab5A and Rab7A,
both important regulators of the endocytic trafficking pathway. We demonstrate
that silencing the expression of either protein results in a decrease in effector
translocation efficiency. These methods can be easily modified to examine other
intracellular and extracellular pathogens that also utilize secretion systems. In
this way, a global picture of host factors involved in bacterial effector
translocation may be revealed.
PMID- 27501081
TI - Nickel-Catalyzed C-H Chalcogenation of Anilines.
AB - The C-H thiolation of aniline derivatives was accomplished with a versatile
nickel(II) catalyst under ligand-free conditions. The robust nature of the nickel
catalysis system was reflected by the C-H thiolation with a good functional group
tolerance and an ample scope, employing anilines possessing removable directing
groups. The widely applicable nickel catalyst also allowed for aniline C-H
selenylations, while mechanistic studies provided strong support that the rate
determining step is the C-H activation.
PMID- 27501078
TI - Role of Base Excision "Repair" Enzymes in Erasing Epigenetic Marks from DNA.
AB - Base excision repair (BER) is one of several DNA repair pathways found in all
three domains of life. BER counters the mutagenic and cytotoxic effects of damage
that occurs continuously to the nitrogenous bases in DNA, and its critical role
in maintaining genomic integrity is well established. However, BER also performs
essential functions in processes other than DNA repair, where it acts on
naturally modified bases in DNA. A prominent example is the central role of BER
in mediating active DNA demethylation, a multistep process that erases the
epigenetic mark 5-methylcytosine (5mC), and derivatives thereof, converting them
back to cytosine. Herein, we review recent advances in the understanding of how
BER mediates this critical component of epigenetic regulation in plants and
animals.
PMID- 27501082
TI - Phosphorus accumulates faster than nitrogen globally in freshwater ecosystems
under anthropogenic impacts.
AB - Combined effects of cumulative nutrient inputs and biogeochemical processes that
occur in freshwater under anthropogenic eutrophication could lead to myriad
shifts in nitrogen (N):phosphorus (P) stoichiometry in global freshwater
ecosystems, but this is not yet well-assessed. Here we evaluated the
characteristics of N and P stoichiometries in bodies of freshwater and their
herbaceous macrophytes across human-impact levels, regions and periods.
Freshwater and its macrophytes had higher N and P concentrations and lower N : P
ratios in heavily than lightly human-impacted environments, further evidenced by
spatiotemporal comparisons across eutrophication gradients. N and P
concentrations in freshwater ecosystems were positively correlated and N : P was
negatively correlated with population density in China. These results indicate a
faster accumulation of P than N in human-impacted freshwater ecosystems, which
could have large effects on the trophic webs and biogeochemical cycles of
estuaries and coastal areas by freshwater loadings, and reinforce the importance
of rehabilitating these ecosystems.
PMID- 27501083
TI - A computational biomarker of idiopathic generalized epilepsy from resting state
EEG.
AB - Epilepsy is one of the most common serious neurologic conditions. It is
characterized by the tendency to have recurrent seizures, which arise against a
backdrop of apparently normal brain activity. At present, clinical diagnosis
relies on the following: (1) case history, which can be unreliable; (2)
observation of transient abnormal activity during electroencephalography (EEG),
which may not be present during clinical evaluation; and (3) if diagnostic
uncertainty occurs, undertaking prolonged monitoring in an attempt to observe EEG
abnormalities, which is costly. Herein, we describe the discovery and validation
of an epilepsy biomarker based on computational analysis of a short segment of
resting-state (interictal) EEG. Our method utilizes a computer model of dynamic
networks, where the network is inferred from the extent of synchrony between EEG
channels (functional networks) and the normalized power spectrum of the clinical
data. We optimize model parameters using a leave-one-out classification on a
dataset comprising 30 people with idiopathic generalized epilepsy (IGE) and 38
normal controls. Applying this scheme to all 68 subjects we find 100% specificity
at 56.7% sensitivity, and 100% sensitivity at 65.8% specificity. We believe this
biomarker could readily provide additional support to the diagnostic process.
PMID- 27501084
TI - A genotype-phenotype correlation study reveals that a non-coding RNA might be
associated with cardiovascular anomalies in fetuses with WHS.
PMID- 27501085
TI - Systematic review of paediatric studies of adverse drug reactions from
pharmacovigilance databases.
AB - OBJECTIVE: To perform a systematic review of studies describing paediatric
adverse drug reactions (ADRs) conducted from national pharmacovigilance
databases. METHODS: A systematic literature search of studies describing results
for paediatric ADRs from national pharmacovigilance databases was performed.
PubMed database, Embase and MEDLINE were searched up to March 2015. The
descriptive studies included were analysed for country of origin, reporters, and
ADR reporting rate, drugs, ADRs and number of fatalities. RESULTS: 20 studies
were identified. Doctors were the largest group of reporters in all the studies,
and with more consumer reports seen in USA. The studies ranged from 3 - 37 years.
The highest ADR reporting rate was 1458 reports per year per million children in
Cuba. Antibiotics and vaccines were the most frequently reported drugs, in almost
all the studies. The most frequent ADRs were skin and nervous system disorders.
The highest proportion of fatalities and serious reports was from North America.
Drugs used for treating attention deficit hyperactivity disorders (ADHD) and
isotretinoin were the most frequently reported drugs for ADRs in North America.
CONCLUSIONS: There were geographical differences in drugs responsible for ADRs
and their seriousness, especially in North America. Very few studies were
conducted in Asia and Latin America, none were found from Africa.
PMID- 27501086
TI - Wind- and Rain-Induced Vibrations Impose Different Selection Pressures on
Multimodal Signaling.
AB - The world is a noisy place, and animals have evolved a myriad of strategies to
communicate in it. Animal communication signals are, however, often multimodal;
their components can be processed by multiple sensory systems, and noise can thus
affect signal components across different modalities. We studied the effect of
environmental noise on multimodal communication in the tungara frog (Physalaemus
pustulosus). Males communicate with rivals using airborne sounds combined with
call-induced water ripples. We tested males under control as well as noisy
conditions in which we mimicked rain- and wind-induced vibrations on the water
surface. Males responded more strongly to a multimodal playback in which sound
and ripples were combined, compared to a unimodal sound-only playback, but only
in the absence of rain and wind. Under windy conditions, males decreased their
response to the multimodal playback, suggesting that wind noise interferes with
the detection of rival ripples. Under rainy conditions, males increased their
response, irrespective of signal playback, suggesting that different noise
sources can have different impacts on communication. Our findings show that noise
in an additional sensory channel can affect multimodal signal perception and
thereby drive signal evolution, but not always in the expected direction.
PMID- 27501087
TI - Communication Value of Mistakes in Dark-Eyed Junco Song.
AB - Sexual signals contain information on individual quality or motivation, and most
explanations for their reliability are based on signal costs. A recent suggestion
is that signaling mistakes, defined as deviations from typical signal design,
provide cues on individual quality, contributing to reliable communication even
when signal design is not costly. We describe several atypical song traits in
dark-eyed juncos (Junco hyemalis) that may be mistakes during song production or
development and occur in up to 6% of songs. These putative mistakes were more
frequent in an urban versus a wildland population, and individuals differed in
their frequency of mistakes. Some atypical signals were more frequent in younger
males or were negatively related to paternity success, supporting the hypothesis
that fewer mistakes indicate individual quality. We also discuss unexpected
results, such as some atypical signals being more frequent in more ornamented
males and in songs with lower performance demands. Song consistency (similarity
across syllable renditions) was positively related to male age and paternity
success; nonetheless, relations with paternity were stronger when looking at the
most deviant syllable renditions, suggesting that the perceptual salience of
large mistakes may mediate receiver responses to song consistency. Results
indicate that signaling mistakes reveal relevant information to play a role in
communication.
PMID- 27501088
TI - Many Paths to a Common Destination: Morphological Differentiation of a
Functionally Convergent Visual Signal.
AB - Understanding the interacting outcomes of selection and historical contingency in
shaping adaptive evolution remains a challenge in evolutionary biology. While
selection can produce convergent outcomes when species occupy similar
environments, the unique history of each species can also influence evolutionary
trajectories and result in different phenotypic end points. The question is to
what extent historical contingency places species on different adaptive pathways
and, in turn, the extent to which we can predict evolutionary outcomes. Among
lizards there are several distantly related genera that have independently
evolved an elaborate extendible dewlap for territorial communication. We
conducted a detailed morphological study and employed new phylogenetic
comparative methods to investigate the evolution of the underlying hyoid that
powers the extension of the dewlap. This analysis showed that there appear to
have been multiple phenotypic pathways for evolving a functionally convergent
dewlap. The biomechanical complexity that underlies this morphological structure
implies that adaptation should have been constrained to a narrow phenotypic
pathway. However, multiple adaptive solutions have been possible in apparent
response to a common selection pressure. Thus, the phenotypic outcome that
subsequently evolved in different genera seems to have been contingent on the
history of the group in question. This blurs the distinction between convergent
and historically contingent adaptation and suggests that adaptive phenotypic
diversity can evolve without the need for divergent natural selection.
PMID- 27501089
TI - Effects of Prior Contest Experience and Contest Outcome on Female Reproductive
Decisions and Offspring Fitness.
AB - Winning or losing a prior contest can influence the outcome of future contests,
but it might also alter subsequent reproductive decisions. For example, losers
may increase their investment in the current breeding attempt if losing a contest
indicates limited prospects for future breeding. Using the burying beetle
Nicrophorus vespilloides, we tested whether females adjust their prehatching and
posthatching reproductive effort after winning or losing a contest with a same
sex conspecific. Burying beetles breed on carcasses of small vertebrates for
which there is fierce intrasexual competition. We found no evidence that winning
or losing a contest influenced reproductive investment decisions in this species.
Instead, we show that a female's prior contest experience (regardless of its
outcome) influenced the amount of posthatching care provided, with downstream
consequences for the female's reproductive output; both winners and losers spent
more time provisioning food to their offspring and produced larger broods than
females with no contest experience. We discuss the wider implications of our
findings and present a conceptual model linking contest-mediated adjustments in
parental investment to population-level processes. We propose that the frequency
of intraspecific contests could both influence and be influenced by population
dynamics in species where contest experience influences the size and/or number of
offspring produced.
PMID- 27501090
TI - How the Magnitude of Prey Genetic Variation Alters Predator-Prey Eco-Evolutionary
Dynamics.
AB - Evolution can alter the stability and dynamics of ecological communities; for
example, prey evolution can drive cyclic dynamics in predator-prey systems that
are not possible in the absence of evolution. However, it is unclear how the
magnitude of additive genetic variation in the evolving species mediates those
effects. In this study, I explore how the magnitude of prey additive genetic
variation determines what effects prey evolution has on the dynamics and
stability of predator-prey systems. I use linear stability analysis to decompose
the stability of a general eco-evolutionary predator-prey model into components
representing the stabilities of the ecological and evolutionary subsystems as
well as the interactions between those subsystems. My results show that with low
genetic variation, the cyclic dynamics and stability of the system are determined
by the ecological subsystem. With increased genetic variation, disruptive
selection always destabilizes stable communities, stabilizing selection can
stabilize or destabilize communities, and prey evolution can alter predator-prey
phase lags. Stability changes occur approximately when the magnitude of genetic
variation balances the (in)stabilities of the ecological and evolutionary
subsystems. I discuss the connections between my stability results and prior
results from the theory of adaptive dynamics.
PMID- 27501091
TI - Multiscale Evaluation of Thermal Dependence in the Glucocorticoid Response of
Vertebrates.
AB - Environmental temperature has profound effects on animal physiology, ecology, and
evolution. Glucocorticoid (GC) hormones, through effects on phenotypic
performance and life history, provide fundamental vertebrate physiological
adaptations to environmental variation, yet we lack a comprehensive understanding
of how temperature influences GC regulation in vertebrates. Using field studies
and meta- and comparative phylogenetic analyses, we investigated how acute change
and broadscale variation in temperature correlated with baseline and stress
induced GC levels. Glucocorticoid levels were found to be temperature and taxon
dependent, but generally, vertebrates exhibited strong positive correlations with
acute changes in temperature. Furthermore, reptile baseline, bird baseline, and
capture stress-induced GC levels to some extent covaried with broadscale
environmental temperature. Thus, vertebrate GC function appears clearly thermally
influenced. However, we caution that lack of detailed knowledge of thermal
plasticity, heritability, and the basis for strong phylogenetic signal in GC
responses limits our current understanding of the role of GC hormones in species'
responses to current and future climate variation.
PMID- 27501092
TI - Discovery of a Giant Chameleon-Like Lizard (Anolis) on Hispaniola and Its
Significance to Understanding Replicated Adaptive Radiations.
AB - We report a new chameleon-like Anolis species from Hispaniola that is
ecomorphologically similar to congeners found only on Cuba. Lizards from both
clades possess short limbs and a short tail and utilize relatively narrow
perches, leading us to recognize a novel example of ecomorphological matching
among islands in the well-known Greater Antillean anole radiation. This discovery
supports the hypothesis that the assembly of island faunas can be substantially
deterministic and highlights the continued potential for basic discovery to
reveal new insights in well-studied groups. Restricted to a threatened band of
midelevation transitional forest near the border of the Dominican Republic and
Haiti, this new species appears to be highly endangered.
PMID- 27501093
TI - Scale-Dependent Community Theory for Streams and Other Linear Habitats.
AB - The maintenance of species diversity occurs at the regional scale but depends on
interacting processes at the full range of lower scales. Although there is a long
history of study of regional diversity as an emergent property, analyses of fully
multiscale dynamics are rare. Here, we use scale transition theory for a
quantitative analysis of multiscale diversity maintenance with continuous scales
of dispersal and environmental variation in space and time. We develop our
analysis with a model of a linear habitat, applicable to streams or coastlines,
to provide a theoretical foundation for the long-standing interest in
environmental variation and dispersal, including downstream drift. We find that
the strength of regional coexistence is strongest when local densities and local
environmental conditions are strongly correlated. Increasing dispersal and
shortening environmental correlations weaken the strength of coexistence
regionally and shift the dominant coexistence mechanism from fitness-density
covariance to the spatial storage effect, while increasing local diversity.
Analysis of the physical and biological determinants of these mechanisms improves
understanding of traditional concepts of environmental filters, mass effects, and
species sorting. Our results highlight the limitations of the binary distinction
between local communities and a species pool and emphasize species coexistence as
a problem of multiple scales in space and time.
PMID- 27501094
TI - Tissue Specificity and Sex-Specific Regulatory Variation Permit the Evolution of
Sex-Biased Gene Expression.
AB - Genetic correlations between males and females are often thought to constrain the
evolution of sexual dimorphism. However, sexually dimorphic traits and the
underlying sexually dimorphic gene expression patterns are often rapidly
evolving. We explore this apparent paradox by measuring the genetic correlation
in gene expression between males and females (Cmf) across broad evolutionary
timescales, using two RNA-sequencing data sets spanning multiple populations and
multiple species. We find that unbiased genes have higher Cmf than sex-biased
genes, consistent with intersexual genetic correlations constraining the
evolution of sexual dimorphism. However, we found that highly sex-biased genes
(both male and female biased) also had higher tissue specificity, and unbiased
genes had greater expression breadth, suggesting that pleiotropy may constrain
the breakdown of intersexual genetic correlations. Finally, we show that genes
with high Cmf showed some degree of sex-specific changes in gene expression in
males and females. Together, our results suggest that genetic correlations
between males and females may be less important in constraining the evolution of
sex-biased gene expression than pleiotropy. Sex-specific regulatory variation and
tissue specificity may resolve the paradox of widespread sex bias within a
largely shared genome.
PMID- 27501095
TI - Complex heterochrony underlies the evolution of Caenorhabditis elegans
hermaphrodite sex allocation.
AB - Hermaphroditic organisms are key models in sex allocation research, yet the
developmental processes by which hermaphrodite sex allocation can evolve remain
largely unknown. Here we use experimental evolution of hermaphrodite-male
(androdioecious) Caenorhabditis elegans populations to quantify the developmental
changes underlying adaptive shifts in hermaphrodite sex allocation. We show that
the experimental evolution of increased early-life self-fertility occurred
through modification of a suite of developmental traits: increased self-sperm
production, accelerated oogenesis and ovulation, and increased embryo retention.
The experimental evolution of increased self-sperm production delayed entry into
oogenesis-as expected, given the sequentially coupled production of self
spermatogenesis and oogenesis. Surprisingly, however, delayed oogenesis onset did
not delay reproductive maturity, nor did it trade-off with gamete or embryo size.
Comparing developmental time dynamics of germline and soma indicates that the
evolution of increased sperm production did not delay reproductive maturity due
to a globally accelerated larval development during the period of self
spermatogenesis. Overall, heterochrony in gametogenesis and soma can explain
adaptive shifts in hermaphrodite sex allocation.
PMID- 27501096
TI - Utility of the Department of Defense Serum Repository in Assessing Deployment
Exposure.
AB - OBJECTIVE: This paper describes why the research project was conducted in terms
of demonstrating the utility of the Department of Defense Serum Repository in
addressing deployment environmental exposures. METHODS: The history deployment
exposure surveillance was reviewed and the rationale for developing validated
biomarkers that were detected in sera in postdeployment samples and compared with
nondeployed controls was described. The goal was to find validated biomarkers
that are associated with both exposures and health outcomes. RESULTS: The
articles in this supplement described novel serum biomarkers that were found to
be associated with deployment exposures and weakly associated with some health
outcomes. CONCLUSIONS: Future research must continue to validate the use of serum
biomarkers when operational contingencies prevent the gold standard collection of
real-time breathing zone samples in deployed service members.
PMID- 27501097
TI - Assessing Health Outcomes After Environmental Exposures Associated With Open Pit
Burning in Deployed US Service Members.
AB - OBJECTIVE: This study assessed the long-term health impact of environmental
exposures associated with open pit burning in deployed US service members.
METHODS: Two hundred individuals deployed to Balad, Iraq, and Bagram,
Afghanistan, with known exposure to open pits, were matched to 200 non-deployed
service members. Both cohorts were observed for adverse health outcomes after
returning from deployment. RESULTS: Slight increased risks were observed for
respiratory diseases in the Bagram cohort (adj RR: 1.259), and for cardiovascular
disease in the Balad cohort (adj RR: 1.072), but the findings were not
significant. The combined deployed cohort showed lower risks for adverse health
outcomes, suggesting a healthy deployer effect. CONCLUSIONS: In conclusion, this
study did not find significantly increased risks for selected health outcomes
after burn pit exposure during deployment among two deployed cohorts compared
with a non-deployed cohort.
PMID- 27501098
TI - Metabolic Pathways and Networks Associated With Tobacco Use in Military
Personnel.
AB - OBJECTIVE: The aim of this study is to use high-resolution metabolomics (HRM) to
identify metabolic pathways and networks associated with tobacco use in military
personnel. METHODS: Four hundred deidentified samples obtained from the
Department of Defense Serum Repository were classified as tobacco users or
nonusers according to cotinine content. HRM and bioinformatic methods were used
to determine pathways and networks associated with classification. RESULTS:
Eighty individuals were classified as tobacco users compared with 320 nonusers on
the basis of cotinine levels at least 10 ng/mL. Alterations in lipid and
xenobiotic metabolism, and diverse effects on amino acid, sialic acid, and purine
and pyrimidine metabolism were observed. Importantly, network analysis showed
broad effects on metabolic associations not simply linked to well-defined
pathways. CONCLUSIONS: Tobacco use has complex metabolic effects that must be
considered in evaluation of deployment-associated environmental exposures in
military personnel.
PMID- 27501099
TI - Deployment-Associated Exposure Surveillance With High-Resolution Metabolomics.
AB - OBJECTIVE: The aim of this study was to assess the suitability of high-resolution
metabolomics (HRM) for measure of internal exposure and effect biomarkers from
deployment-related environmental hazards. METHODS: HRM provides extensive
coverage of metabolism and data relevant to a broad spectrum of environmental
exposures. This review briefly describes the analytic platform, workflow, and
recent applications of HRM as a prototype environmental exposure surveillance
system. RESULTS: Building upon techniques available for contemporary occupational
medicine and exposure sciences, HRM methods are able to integrate external
exposures, internal body burden of environmental agents, and relevant biological
responses with health outcomes. CONCLUSIONS: Systematic analysis of existing
Department of Defense Serum Repository samples will provide a high-quality, cross
sectional reference dataset for deployment-associated exposures while at the same
time establishing a foundation for precision medicine.
PMID- 27501100
TI - Airborne Dioxins, Furans, and Polycyclic Aromatic Hydrocarbons Exposure to
Military Personnel in Iraq.
AB - OBJECTIVES: The objective of this study was to use ambient polycyclic aromatic
hydrocarbon (PAH), polychlorinated dibenzo-p-dioxins (PCDD), and polychlorinated
dibenzofurans (PCDF) concentrations measured at Joint Base Balad in Iraq in 2007
to identify the sources of these species and their spatial patterns. METHODS: The
ratios of the measured species were compared with literature data for likely
emission sources. Using the multiple site measurements on specific days, contour
maps have been drawn using inverse distance weighting (IDW). RESULTS: These
analyses suggest multiple sources, including the burn pit (primarily a source of
PCDD/PCDFs), the transportation field (primarily as source of PAHs), and other
sources of PAHs that include aircraft, space heating, and diesel power
generation. CONCLUSIONS: The nature and locations of the sources were identified.
PCDD/PCDFs were emitted by the burn pit. Multiple PAH sources exist across the
base.
PMID- 27501101
TI - Introduction to Department of Defense Research on Burn Pits, Biomarkers, and
Health Outcomes Related to Deployment in Iraq and Afghanistan.
AB - OBJECTIVE: This paper provides an overview of our study that was designed to
assess the health impact of environmental exposures to open pit burning in
deployed troops. METHODS: The rationale for the study and the structure of the
research plan was laid out. An overview of each article in the supplement was
provided. The cohort of deployed Service members was assessed for airborne
exposure, relevant biomarkers, and health outcomes following deployment to Balad,
Iraq, and/or Bagram, Afghanistan. RESULTS: Polycyclic aromatic hydrocarbon (PAH)
exposures were elevated, and serum biomarkers were statistically different
postdeployment. Associations were noted between PAHs and dioxins and microRNAs.
Some health outcomes were evident in deployers compared with nondeployers.
CONCLUSIONS: Future research will examine the associations between demographic
variables, smoking status, biomarker levels, and related health outcomes.
PMID- 27501102
TI - Source Apportionment of Airborne Dioxins, Furans, and Polycyclic Aromatic
Hydrocarbons at a United States Forward Operating Air Base During the Iraq War.
AB - OBJECTIVES: The objective was to apportion the sources of the ambient polycyclic
aromatic hydrocarbon (PAH), polychlorinated dibenzo-p-dioxin (PCDD) and
polychlorinated dibenzofuran concentrations measured at Joint Base Balad in Iraq.
METHODS: Positive matrix factorization (PMF) was applied to the data to obtain
the chemical profiles and contribution time series of the PAHs, PCDDs, and PCDFs.
Conditional probability function (CPF) analyses were performed to assess the
source directionality relative to the monitoring sites. RESULTS: Three source
types were identified and apportioned. The sources were: the burn pit, diesel
vehicles and generators, and aircraft emissions. The CPF plots were consistent
with the assigned source types. CONCLUSIONS: The PCDDs and PCDFs originated
primarily from the burn pit. Higher molecular weight PAHs were associated with
vehicle emissions while the aircraft emissions were enriched in low molecular
weight PAHs.
PMID- 27501103
TI - Environmental Air Sampling Near Burn Pit and Incinerator Operations at Bagram
Airfield, Afghanistan.
AB - OBJECTIVE: This study presents environmental air samples collected at a US
military installation with a solid waste disposal facility (SWDF) containing a
burn pit from 2005 through 2012 and compared these results with occupational
(breathing zone) samples. METHODS: Particulate matter (PM) environmental samples
were collected as part of the installation monitoring program. Service Members in
four security positions were monitored for PM and acrolein occupational
exposures. RESULTS: The highest recorded PM2.5 concentration occurred at the
SWDF. A highly populated sampling site, the Bazaar site, had the highest mean
PM10, with the SWDF following in second. Acrolein and respirable PM were
considerably higher in the breathing zone samples than environmental samples.
CONCLUSIONS: The diversity of results support the concept of a complex
environment with multiple polluting sources and changing meteorological and
operational conditions.
PMID- 27501104
TI - Pilot Metabolome-Wide Association Study of Benzo(a)pyrene in Serum From Military
Personnel.
AB - OBJECTIVE: A pilot study was conducted to test the feasibility of using
Department of Defense Serum Repository (DoDSR) samples to study health and
exposure-related effects. METHODS: Thirty unidentified human serum samples were
obtained from the DoDSR and analyzed for normal serum metabolites with high
resolution mass spectrometry and serum levels of free benzo(a)pyrene (BaP) by gas
chromatography-mass spectrometry. Metabolic associations with BaP were determined
using a metabolome-wide association study (MWAS) and metabolic pathway
enrichment. RESULTS: The serum analysis detected normal ranges of glucose,
selected amino acids, fatty acids, and creatinine. Free BaP was detected in a
broad concentration range. MWAS of BaP showed associations with lipids, fatty
acids, and sulfur amino acid metabolic pathways. CONCLUSION: The results show
that the DoDSR samples are of sufficient quality for chemical profiling of DoD
personnel.
PMID- 27501105
TI - High-Resolution Metabolomics Assessment of Military Personnel: Evaluating
Analytical Strategies for Chemical Detection.
AB - OBJECTIVE: The aim of this study was to maximize detection of serum metabolites
with high-resolution metabolomics (HRM). METHODS: Department of Defense Serum
Repository (DoDSR) samples were analyzed using ultrahigh resolution mass
spectrometry with three complementary chromatographic phases and four ionization
modes. Chemical coverage was evaluated by number of ions detected and accurate
mass matches to a human metabolomics database. RESULTS: Individual HRM platforms
provided accurate mass matches for up to 58% of the KEGG metabolite database.
Combining two analytical methods increased matches to 72% and included
metabolites in most major human metabolic pathways and chemical classes.
Detection and feature quality varied by analytical configuration. CONCLUSIONS:
Dual chromatography HRM with positive and negative electrospray ionization
provides an effective generalized method for metabolic assessment of military
personnel.
PMID- 27501106
TI - Detection of Serum microRNAs From Department of Defense Serum Repository:
Correlation With Cotinine, Cytokine, and Polycyclic Aromatic Hydrocarbon Levels.
AB - OBJECTIVE: The aim of this study was to investigate whether serum samples from
the Department of Defense Serum Repository (DoDSR) are of sufficient quality to
detect microRNAs (miRNAs), cytokines, immunoglobulin E (IgE), and polycyclic
aromatic hydrocarbons (PAHs). METHODS: MiRNAs were isolated and quantified by
polymerase chain reaction (PCR) array. Cytokines and chemokines related to
inflammation were measured using multiplex immunoassays. Cotinine and IgE were
detected by enzyme-linked immunoassay (ELISA) and PAHs were detected by Liquid
Chromatography/Mass Spectroscopy. RESULTS: We detected miRNAs, cytokines, IgE,
and PAHs with high sensitivity. Eleven of 30 samples tested positive for cotinine
suggesting tobacco exposure. Significant associations between serum cotinine,
cytokine, IgE, PAHs, and miRNA were discovered. CONCLUSION: We successfully
quantified over 200 potential biomarkers of occupational exposure from DoDSR
samples. The stored serum samples were not affected by hemolysis and represent a
powerful tool for biomarker discovery and analysis in retrospective studies.
PMID- 27501107
TI - Polycyclic Aromatic Hydrocarbons and Polychlorinated Dibenzo-p
Dioxins/Dibenzofurans in Microliter Samples of Human Serum as Exposure
Indicators.
AB - OBJECTIVE: The objectives were: 1) measure polycyclic aromatic hydrocarbons
(PAHs), polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in
100 MUL of human serum and 2) assess PAH and PCDD/PCDF as markers of burn pit
exposures during military deployments. METHODS: PAHs and PCDDs/PCDFs were
analyzed in 100 MUL serum samples collected pre- and post-deployment from 200
persons deployed to Iraq or Afghanistan (CASE); 200 persons not deployed
(CONTROL) with gas chromatography/mass spectrometry. RESULTS: Naphthalene was
found in ~83% of the samples and was statistically different between post
deployment CASE personnel and pre-deployment. 1,2,3,4,6,7,8-Heptachlorodibenzo-p
dioxin, Octachlorodibenzo-p-dioxin, 1,2,3,7,8,9-Hexachlorodibenzofuran, and
1,2,3,4,6,7,8-Heptachlorodibenzofuran were found in ~38% of samples.
Concentrations were significantly different between CASE and CONTROL and between
pre- and post-deployment samples. CONCLUSIONS: PAH and PCDD/PCDF in serum can
serve as exposure markers and measurements in small volumes is feasible for
quantifying exposure to burn pits.
PMID- 27501108
TI - High-Resolution Metabolomics for Nutrition and Health Assessment of Armed Forces
Personnel.
AB - OBJECTIVE: The aim of this study was to test the utility of high-resolution
metabolomics (HRM) for analysis of nutritional status and health indicators in
military personnel. METHODS: Serum samples from 400 military personnel were
obtained from the Department of Defense Serum Repository (DoDSR) and analyzed for
metabolites related to nutrition and health status. Metabolic profile
organization was studied using modulated modularity clustering (MMC). RESULTS:
HRM provided quantitative measures of 61 metabolites across chemical classes for
use as nutritional and clinical biomarkers. Levels were comparable to reported
values except for arginine and glutamine, which were above and below reference
ranges, respectively. MMC generated five clusters, three of which were associated
and contained amino acids. The others contained lipids and mitochondria-related
metabolites. CONCLUSIONS: HRM analysis of serum is suitable for real-time and/or
retrospective evaluation of nutrition and health status of specific military
cohorts.
PMID- 27501109
TI - MicroRNAs as Novel Biomarkers of Deployment Status and Exposure to
Polychlorinated Dibenzo-p-Dioxins/Dibenzofurans.
AB - OBJECTIVE: To determine if service members deployed to locations with open air
burn pits have different serum microRNA (miRNA) profiles after deployment
compared with length-of-service matched, non-deployed individuals. We also tested
for correlations between miRNA and serum levels of Polychlorinated Dibenzo-p
Dioxins/Dibenzofurans (PCDD/PCDFs). METHODS: MiRNAs were isolated and quantified
by PCR array. Groups were analyzed for differences in miRNA expression.
Correlations between serum miRNA and PCDD/PCDFs were assessed with a linear
regression model. RESULTS: Several miRNAs were differentially expressed after
deployment and a partially overlapping set of miRNAs were identified between
deployed and non-deployed individuals. Significant correlations between miRNAs
and PCDD/PCDFs were identified. CONCLUSIONS: Serum miRNA levels show a link
between deployment to locations with open burn pits and environmental exposures
that can take place during deployment.
PMID- 27501110
TI - MicroRNA Expression Profiling of the Armed Forces Health Surveillance Branch
Cohort for Identification of "Enviro-miRs" Associated With Deployment-Based
Environmental Exposure.
AB - OBJECTIVE: The aim of this study was to identify serum microRNA (miRNA)
biomarkers that indicate deployment-associated exposures in service members at
military installations with open burn pits. Another objective was to determine
detection rates of miRNAs in Department of Defense Serum Repository (DoDSR)
samples with a high-throughput methodology. METHODS: Low-volume serum samples (n
= 800) were profiled by miRNA-capture isolation, pre-amplification, and
measurement by a quantitative PCR-based OpenArray platform. Normalized
quantitative cycle values were used for differential expression analysis between
groups. RESULTS: Assay specificity, dynamic range, reproducibility, and detection
rates by OpenArray passed target desired specifications. Serum abundant miRNAs
were consistently measured in study specimens. Four miRNAs were differentially
expressed in the case deployment group subjects. CONCLUSIONS: miRNAs are suitable
RNA species for biomarker discovery in the DoDSR serum specimens. Serum miRNAs
are candidate biomarkers for deployment and environmental exposure in military
service members.
PMID- 27501111
TI - Piloting CenteringParenting in Two Alberta Public Health Well-Child Clinics.
AB - OBJECTIVES: To pilot a group health service delivery model, CenteringParenting,
for new parents, to assess its feasibility and impact on maternal and infant
outcomes. DESIGN AND SAMPLE: Families attended six, 2-hr group sessions in their
child's first year of life with three to seven other families. Health
assessments, parent-led discussions, and vaccinations occurred within the group.
MEASURES: Demographic, breastfeeding, vaccination, maternal psychosocial health,
parenting, and satisfaction data were collected and compared to a representative
cohort. RESULTS: Four groups ran in two clinics. Four to eight parent/infant
dyads participated in each group, 24 total dyads. Most participating parents were
mothers. Dyads in the group model received 12 hr of contact with Public Health
over the year compared to 3 hr in the typical one-on-one model. Participants were
younger, more likely to have lower levels of education, and lower household
income than the comparison group. Parents reported improvements in parenting
experiences following the program. At 4 months, all CenteringParenting babies
were vaccinated compared to 95% of babies in the comparison group. CONCLUSIONS:
The pilot was successfully completed. Additional research is required to examine
the effectiveness of CenteringParenting. Data collected provide insight into
potential primary outcomes of interest and informs larger, rigorously designed
longitudinal studies.
PMID- 27501112
TI - Herpes virus reactivation after initiation of interferon-free antiviral agents in
HIV-HCV-coinfected subjects: a new immune restoration disease?
AB - We report four HCV-HIV-coinfected patients who developed herpes zoster or muco
cutaneous herpes virus disease shortly after starting interferon-free antiviral
treatment for HCV. We suggest that in our patients the prompt clearance of HCV
following direct-acting antivirals leads to a paradoxical effect on the innate
and adaptive immune system mediating the reactivation of herpetic infection.
PMID- 27501113
TI - Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer
cells.
AB - Ataxia telangiectasia and Rad3-related (ATR) proteins are sensors of DNA damage,
which induces homologous recombination (HR)-dependent repair. ATR is a master
regulator of DNA damage repair (DDR), signaling to control DNA replication, DNA
repair and apoptosis. Therefore, the ATR pathway might be an attractive target
for developing new drugs. This study was designed to investigate the antitumor
effects of the ATR inhibitor, AZD6738 and its underlying mechanism in human
breast cancer cells. Growth inhibitory effects of AZD6738 against human breast
cancer cell lines were studied using a 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (methyl thiazolyl tetrazolium, MTT) assay. Cell cycle
analysis, Western blotting, immunofluorescence and comet assays were also
performed to elucidate underlying mechanisms of AZD6738 action. Anti
proliferative and DDR inhibitory effects of AZD6738 were demonstrated in human
breast cancer cell lines. Among 13 cell lines, the IC50 values of nine cell lines
were less than 1 MUmol/L using MTT assay. Two cell lines, SK-BR-3 and BT-474,
were chosen for further evaluation focused on human epidermal growth factor
receptor 2 (HER2)-positive breast cancer cells. Sensitive SK-BR-3 but not the
less sensitive BT-474 breast cancer cells showed increased level of apoptosis and
S phase arrest and reduced expression levels of phosphorylated check-point kinase
1 (CHK1) and other repair markers. Decreased functional CHK1 expression induced
DNA damage accumulation due to HR inactivation. AZD6738 showed synergistic
activity with cisplatin. Understanding the antitumor activity and mechanisms of
AZD6738 in HER2-positive breast cancer cells creates the possibility for future
clinical trials targeting DDR in HER2-positive breast cancer treatment.
PMID- 27501114
TI - Automated Lipid Bilayer Membrane Formation Using a Polydimethylsiloxane Thin
Film.
AB - An artificial lipid bilayer, or black lipid membrane (BLM), is a powerful tool
for studying ion channels and protein interactions, as well as for biosensor
applications. However, conventional BLM formation techniques have several
drawbacks and they often require specific expertise and laborious processes. In
particular, conventional BLMs suffer from low formation success rates and
inconsistent membrane formation time. Here, we demonstrate a storable and
transportable BLM formation system with controlled thinning-out time and enhanced
BLM formation rate by replacing conventionally used films
(polytetrafluoroethylene, polyoxymethylene, polystyrene) to polydimethylsiloxane
(PDMS). In this experiment, a porous-structured polymer such as PDMS thin film is
used. In addition, as opposed to conventionally used solvents with low viscosity,
the use of squalene permitted a controlled thinning-out time via slow solvent
absorption by PDMS, prolonging membrane lifetime. In addition, by using a mixture
of squalene and hexadecane, the freezing point of the lipid solution was
increased (~16 degrees C), in addition, membrane precursors were produced that
can be indefinitely stored and readily transported. These membrane precursors
have reduced BLM formation time of < 1 hr and achieved a BLM formation rate of
~80%. Moreover, ion channel experiments with gramicidin A demonstrated the
feasibility of the membrane system.
PMID- 27501115
TI - High-sensitivity cardiac troponin testing for primary care: analytical assay
considerations required before widespread implementation.
PMID- 27501116
TI - Not all performance validity tests are created equal: The role of recollection
and familiarity in the Test of Memory Malingering and Word Memory Test.
AB - INTRODUCTION: The Test of Memory Malingering (TOMM) and the Word Memory Test
(WMT) are both performance validity tests (PVTs) that use a two-alternative
forced-choice (2AFC) recognition memory format. Several studies have reported
that these tests are susceptible to cognitive impairment and that the WMT is more
susceptible than the TOMM. The current study explored components of recognition
memory (i.e., conscious recollection and familiarity) underlying the TOMM and WMT
to identify factors that make them susceptible and resilient to cognitive
impairment. METHOD: Fifty-four nonclinical undergraduate research participants
were administered the TOMM and WMT while providing introspective judgments about
their recognition memory using the remember/know/guess procedure. In addition,
half of participants were administered dual-task interference, a manipulation
intended to reduce recollection, during these tests, while the other half
completed these tests without interference. Standard cutoffs on the TOMM and WMT
were explored, as well as alternative cutoffs based on TOMM Trial 1 scores.
RESULTS: The WMT was more impacted by dual-task interference than standard TOMM
cutoff trials, while alternative TOMM cutoff trials were equally impacted by dual
task interference relative to the WMT. Dual-task interference reduced
recollection on these tests, but spared familiarity. Standard TOMM trials and the
WMT were relatively comparable on levels of recollection, but familiarity
contributed more to the TOMM than to the WMT. Alternative TOMM trials possessed
lower familiarity and recollection than standard TOMM trials and lower
recollection than the WMT. CONCLUSIONS: Reduced recollection places examinees at
risk of failing the TOMM and WMT, while familiarity contributes to the relative
resilience of the standard TOMM. Future development of 2AFC recognition memory
PVTs should attempt to maximize the contribution of familiarity to their
completion.
PMID- 27501117
TI - Enhancing the Thermal Conductance of Polymer and Sapphire Interface via Self
Assembled Monolayer.
AB - Interfacial thermal conductance (ITC) receives enormous consideration because of
its significance in determining thermal performance of hybrid materials, such as
polymer based nanocomposites. In this study, the ITC between sapphire and
polystyrene (PS) was systematically investigated by time domain thermoreflectance
(TDTR) method. Silane based self-assembled monolayers (SAMs) with varying end
groups, -NH2, -Cl, -SH and -H, were introduced into sapphire/PS interface, and
their effects on ITC were investigated. The ITC was found to be enhanced up by a
factor of 7 through functionalizing the sapphire surface with SAM, which ends
with a chloride group (-Cl). The results show that the enhancement of the thermal
transport across the SAM-functionalized interface comes from both strong covalent
bonding between sapphire and silane-based SAM, and the high compatibility between
the SAM and PS. Among the SAMs studied in this work, we found that the ITC almost
linearly depends on solubility parameters, which could be the dominant factor
influencing on the ITC compared with wettability and adhesion. The SAMs serve as
an intermediate layer that bridges the sapphire and PS. Such a feature can be
applied to ceramic-polymer immiscible interfaces by functionalizing the ceramic
surface with molecules that are miscible with the polymer materials. This
research provides guidance on the design of critical-heat transfer materials such
as composites and nanofluids for thermal management.
PMID- 27501118
TI - Multimodality therapy for locally-advanced thymic epithelial tumors: where are we
now?
PMID- 27501119
TI - Pulse modulated radiofrequency exposure influences cognitive performance.
AB - PURPOSE: To investigate whether exposure to pulse modulated radiofrequency (PM
RF) influences human cognitive performance, and whether it does so in a dose
dependent manner. MATERIALS AND METHODS: Thirty-six healthy adults participated
in a randomized, double-blind, counterbalanced provocation study. Cognitive
performance was assessed using a visual discrimination task and a modified
Sternberg working memory task, which were calibrated to individual performance
levels in a preliminary testing session. An sXh920 planar exposure system was
used to generate a 920 MHz GSM-like signal, providing three conditions (peak
spatial SAR averaged over 10 g) of 0 W/kg (sham), 1 W/kg (low RF) and 2 W/kg
(high RF). RESULTS: A significant decrease in reaction time (RT) in the Sternberg
working memory task was found during exposure compared to sham. This effect was
not dose-dependent. CONCLUSIONS: Cognitive performance was shown to be faster
under PM RF conditions, relative to sham, in a working memory task. While the
majority of the literature has not found effects of PM RF exposure on cognitive
performance, it is possible that the methodological improvements employed in the
present study increased sensitivity, and thus the ability to detect potential
effects.
PMID- 27501120
TI - Noninvasive Continuous Hemoglobin Monitoring in Combat Casualties: A Pilot Study.
AB - OBJECTIVE: To describe the accuracy and precision of noninvasive hemoglobin
measurement (SpHb) compared with laboratory or point-of-care Hb, and SpHb ability
to trend in seriously injured casualties. METHODS: Observational study in a
convenience sample of combat casualties undergoing resuscitation at two US
military trauma hospitals in Afghanistan. SpHb was obtained using the Masimo
Rainbow SET (Probe Rev E/Radical-7 Pulse CO-Oximeter v 7.6.2.1). Clinically
indicated Hb was analyzed with a Coulter or iStat and compared with simultaneous
SpHb values. RESULTS: Twenty-three patients were studied (ISS 20 +/- 9.8; age 29
+/- 9 years; male 97%; 100% intubated). Primary injury cause: improvised
explosive device (67%) or gunshot (17%). There were 49 SpHb-Hb pairs (median 2
per subject). Bias: 0.3 +/- 1.6 g/dL (95% LOA -2.4, 3.4 g/dL). The SpHb-Hb
difference < +/- 1 g/dL in 37% of pairs. Eighty-six percent of pairs changed in a
similar direction. Using an absolute change in Hb of >1 g/dL, a concurrent
absolute change in SpHb of >1 g/dL had a sensitivity: 61%, specificity 85%,
positive predictive value: 80%, and a negative predictive value: 69%. The SpHb
signal was present in 4643 of 6137 min monitored (76%). CONCLUSIONS: This was the
first study to describe continuous SpHb in seriously injured combat casualties.
Using a threshold of 1 g/dL previously specified in the literature, continuous
SpHb is not precise enough to serve as sole transfusion trigger in trauma
patients. Further research is needed to determine if it is useful for trending Hb
changes or as an early indicator of deterioration in combat casualties.
PMID- 27501121
TI - Is there an association between study size and reporting of study quality in
dermatological clinical trials? A meta-epidemiological review.
PMID- 27501122
TI - Outcomes of patients with renal monoclonal immunoglobulin deposition disease.
AB - Recent reports suggest that deep hematologic responses to chemotherapy are
associated with improved renal outcomes in monoclonal immunoglobulin deposition
disease (MIDD). Here we describe the long term outcomes and identify prognostic
factors after first line treatment of the largest reported series of patients
with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen
at Mayo Clinic, MN. Renal responses were defined using criteria used for light
chain amyloidosis (AL) or those used by the IMWG. Sixty-one (69%) patients had a
GFR < 30 mL/min/1.73 m2 and 16 (18%) were on renal replacement therapy at
diagnosis. The interval between albuminuria or elevation in creatinine and MIDD
diagnosis was 12 months suggesting a delay in diagnosis. Thirty-seven patients
(42%) had at least a hematologic CR/VGPR. Fifty-three (60%) received an
autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)-based
treatments. Patients receiving ASCT or PI-based therapies were more likely to
achieve at least a hematologic CR/VGPR compared to those receiving other
therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were
more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year
overall and renal survival for the entire cohort was 67% and 57%, respectively.
In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m2 and a renal response
(using AL or IMWG criteria) were independently predictive of progression to
dialysis. This study confirms that deep hematologic responses, best achieved with
ASCT or PI-based therapies, are a prerequisite to achieving renal responses. Am.
J. Hematol. 91:1123-1128, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27501123
TI - Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological
Brain Function.
AB - The oculomotor system involves a large number of brain areas including parts of
the basal ganglia, and various neurodegenerative diseases including Parkinson's
and Huntington's can disrupt it. People with Parkinson's disease, for example,
tend to have increased saccadic latencies. Consequently, the quantitative
measurement of saccadic eye movements has received considerable attention as a
potential biomarker for neurodegenerative conditions. A lot more can be learned
about the brain in both health and disease by observing what happens to eye
movements when the function of specific brain areas is perturbed. Deep brain
stimulation is a surgical intervention used for the management of a range of
neurological conditions including Parkinson's disease, in which stimulating
electrodes are placed in specific brain areas including several sites in the
basal ganglia. Eye movement measurements can then be made with the stimulator
systems both off and on and the results compared. With suitable experimental
design, this approach can be used to study the pathophysiology of the disease
being treated, the mechanism by which DBS exerts it beneficial effects, and even
aspects of normal neurophysiology.
PMID- 27501124
TI - A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of
Intraocular Pressure.
AB - Retinal ischemia-reperfusion (I/R) is a pathophysiological process contributing
to cellular damage in multiple ocular conditions, including glaucoma, diabetic
retinopathy, and retinal vascular occlusions. Rodent models of I/R injury are
providing significant insights into mechanisms and treatment strategies for human
I/R injury, especially with regard to neurodegenerative damage in the retinal
neurovascular unit. Presented here is a protocol for inducing retinal I/R injury
in mice through elevation of intraocular pressure (IOP). In this protocol, the
ocular anterior chamber is cannulated with a needle, through which flows the drip
of an elevated saline reservoir. Using this drip to raise IOP above systolic
arterial blood pressure, a practitioner temporarily halts inner retinal blood
flow (ischemia). When circulation is reinstated (reperfusion) by removal of the
cannula, severe cellular damage ensues, resulting ultimately in retinal
neurodegeneration. Recent studies demonstrate inflammation, vascular
permeability, and capillary degeneration as additional elements of this model.
Compared to alternative retinal I/R methodologies, such as retinal arterial
ligation, retinal I/R injury by elevated IOP offers advantages in its anatomical
specificity, experimental tractability, and technical accessibility, presenting
itself as a valuable tool for examining neuronal pathogenesis and therapy in the
retinal neurovascular unit.
PMID- 27501125
TI - Separating and Recycling Plastic, Glass, and Gallium from Waste Solar Cell
Modules by Nitrogen Pyrolysis and Vacuum Decomposition.
AB - Many countries have gained benefits through the solar cells industry due to its
high efficiency and nonpolluting power generation associated with solar energy.
Accordingly, the market of solar cell modules is expanding rapidly in recent
decade. However, how to environmentally friendly and effectively recycle waste
solar cell modules is seldom concerned. Based on nitrogen pyrolysis and vacuum
decomposition, this work can successfully recycle useful organic components,
glass, and gallium from solar cell modules. The results were summarized as
follows: (i) nitrogen pyrolysis process can effectively decompose plastic.
Organic conversion rate approached 100% in the condition of 773 K, 30 min, and
0.5 L/min N2 flow rate. But, it should be noted that pyrolysis temperature should
not exceed 773 K, and harmful products would be increased with the increasing of
temperature, such as benzene and its derivatives by GC-MS measurement; (ii)
separation principle, products analysis, and optimization of vacuum decomposition
were discussed. Gallium can be well recycled under temperature of 1123 K, system
pressure of 1 Pa and reaction time of 40 min. This technology is quite
significant in accordance with the "Reduce, Reuse, and Recycle Principle" for
solid waste, and provides an opportunity for sustainable development of
photovoltaic industry.
PMID- 27501126
TI - Inflammatory bowel disease: adherence to immunomodulators in a biological therapy
era.
AB - BACKGROUND: Combination therapy, with anti-tumor necrosis factor-alpha agents and
immunomodulators, is the most effective option to induce and maintain remission
in inflammatory bowel disease (IBD). Infliximab, with its administration
features, determines particular conditions of adherence; the same is not possible
with thiopurines. Nevertheless, research on adherence to these treatments is
scarce. Nonadherence worsens the prognosis of IBD. AIM: (a) Assess adherence to
immunomodulators and (b) determine therapeutic nonadherence predictors. PATIENTS
AND METHODS: We included all IBD outpatients consecutively evaluated over a 6
month period in our center. Participants completed a study-specific questionnaire
on IBD, IBD therapeutic adherence (Morisky Medication Adherence Scale-8-item),
Therapeutics Complexity questionnaire, Beliefs about Medication questionnaire,
and Hospital Anxiety and Depression Scale. RESULTS: A total of 112 patients under
azathioprine were considered; 49.1% were also under anti-tumor necrosis factor
alpha. Self-assessed questionnaire showed that 70.5% were adherent to
immunosuppression. Similar adherence was found with and without infliximab (68.4%
monotherapy vs. 72.7%-combination therapy; P=0.61). Nonintentional nonadherence
was documented in 57.6%; 42.4% reported voluntary nonadherence. Nonadherence was
higher in male patients [odds ratio (OR): 3.79; 95% confidence interval (CI): 1.2
11.95; P=0.023], younger patients (OR: 0.93; 95% CI: 0.87-0.98; P=0.01),
nonsmokers (OR: 4.90; 95% CI: 1.22-19.73; P=0.025), and those who had depression
(OR: 2.22; 95% CI: 1.36-3.62; P=0.001). Most of the IBD patients believed in the
necessity of maintaining immunosuppression (86.7%), but 36.6% reported concerns
about drugs. CONCLUSION: Nonadherence to thiopurines plays a significant role in
IBD. Nonetheless, it does not increase with association with biological agents.
Involuntary nonadherence is higher. Male sex, younger age, nonsmoker, and
presence of depression were independent predictors of nonadherence to
immunomodulators. More than one-third of IBD patients had concerns about drugs.
Optimizing the discussion on patients' concerns to overcome perceptual barriers
related to drugs may obviate the negative course of IBD related to nonadherence.
PMID- 27501127
TI - Dexmedetomidine for the treatment of hyperactive delirium refractory to
haloperidol in non-intubated patients.
PMID- 27501128
TI - Neonatal hepatitis B vaccination impaired the behavior and neurogenesis of mice
transiently in early adulthood.
AB - The immune system plays a vital role in brain development. The hepatitis B
vaccine (HBV) is administered to more than 70% of neonates worldwide. Whether
this neonatal vaccination affects brain development is unknown. Newborn C57BL/6
mice were injected intraperitoneally with HBV or phosphate-buffered saline. HBV
induced impaired behavioral performances and hippocampal long-term potentiation
at 8 weeks (w) of age without influence at 4 or 12w. At 6w, there was decreased
neurogenesis, M1 microglial activation and a neurotoxic profile of neuroimmune
molecule expression [increased tumor necrosis factor-alpha and reduced interferon
(IFN)-gamma, brain-derived neurotrophic factor and insulin-like growth factor-1]
in the hippocampus of the HBV-vaccinated mice. In the serum, HBV induced
significantly higher levels of interleukin (IL)-4, indicating a T helper (Th)-2
bias. Moreover, the serum IFN-gamma/IL-4 ratio was positively correlated with the
levels of neurotrophins and neurogenesis in the hippocampus at the individual
level. These findings suggest that neonatal HBV vaccination of mice results in
neurobehavioral impairments in early adulthood by inducing a proinflammatory and
low neurotrophic milieu in the hippocampus, which follows the HBV-induced
systemic Th2 bias.
PMID- 27501129
TI - Monoclonal gammopathy of cutaneous significance: review of a relevant concept.
AB - Some dermatologic entities are strongly associated with the presence of a
monoclonal gammopathy. They should be referred to as monoclonal gammopathy of
cutaneous significance (MGCS). A short review of the main entities that fit into
the spectrum of MGCS is provided. Amyloidosis, macroglobulinoderma and follicular
hyperkeratotic spicules result from extravascular immunoglobulin or
immunoglobulin-related protein deposition. Skin findings include papules and
plaques, follicular spicules, purpura, haemorrhagic bullae, macroglossia and nail
changes. The skin findings in cryoglobulinemia (CG) result from vascular
immunoglobulin deposition, either as immune complexes within the vessel walls in
mixed CG or within the lumina of small vessels in monoclonal CG. Mixed CG
manifests as palpable purpura of leukocytoclastic vasculitis, and monoclonal CG
as stellar and/or retiform purpura that can evolve into extensive skin necrosis.
In some rare instances, immunoglobulins have a specific biological activity. This
is, for example, the case when they bind lipoproteins that precipitate and induce
hypocomplementemic xanthomas. Xanthoderma related to antiflavin activity of the
monoclonal component or acquired angioedema related to anti-C1INH activity is
other example. Abnormal cytokine secretion is the hallmark of some entities. High
vascular endothelial growth factor levels correlate with some of the skin
manifestations of the Polyneuropathy organomegaly endocrinopathy monoclonal
component skin changes syndrome, such as hypertrichosis or the adenopathy and
extensive skin patch overlying plasmacytoma syndrome. All the clinical
manifestations of the Schnitzler syndrome are IL-1 mediated. In other MGCS, such
as scleromyxedema, Clarkson syndrome, TEMPI syndrome, cutis laxa and the
neutrophilic dermatoses, the link between the monoclocal component and the entity
is clearly established, but not understood so far.
PMID- 27501130
TI - Prediction of cardiovascular events with levels of proprotein convertase
subtilisin/kexin type 9: A systematic review and meta-analysis.
AB - BACKGROUND AND AIMS: Inhibition of proprotein convertase subtilisin/kexin type 9
(PCSK9) reduces atherogenic lipoproteins and could lead to reduction of
cardiovascular (CV) events. However, it is unclear whether blood PCSK9 levels
predict future CV events. We performed a meta-analysis of all longitudinal
studies to determine the ability of PCSK9 levels to predict risk of future CV
events. METHODS: A comprehensive search of electronic databases was conducted up
to February 2016. Longitudinal studies that reported events or relative risk (RR)
estimates with 95% confidence intervals (CI) were included. RESULTS: All 9
studies included (12,081 participants, mean follow-up 6.62 years) reported
results on total CV events. The pooled RR of total CV events for an increase in
baseline PCSK9 by 1 standard deviation (SD) was 1.098 (95% CI, 1.02-1.18),
corresponding to a risk increase of 10% (Z = 2.43, p = 0.015). The pooled RR of
total CV events for subjects categorized in the highest tertile of baseline PCSK9
was 1.228 (95% CI, 1.035-1.457), corresponding to a risk increase of 23% (Z =
2.35, p = 0.019). When pooled estimates were derived independently for low- and
high-CV risk populations, baseline PCSK9 levels predicted total CV events only in
apparently healthy subjects (RR = 1.13, 95% CI: 1.050-1.222, Z = 3.21, p = 0.001)
and not in populations with established CV or renal disease (RR = 1.09, 95% CI:
0.961-1.23, Z = 1.33, p = 0.182). CONCLUSIONS: PCSK9 levels are modestly but
significantly associated with increased risk of total CV events. These results
suggest a predictive role of PCSK9 levels on CV health and support the possible
clinical role of PCSK9 inhibitors.
PMID- 27501131
TI - Computational Method for the Systematic Identification of Analog Series and Key
Compounds Representing Series and Their Biological Activity Profiles.
AB - A computational methodology is introduced for detecting all unique series of
analogs in large compound data sets, regardless of chemical relationships between
analogs. No prior knowledge of core structures or R-groups is required, which are
automatically determined. The approach is based upon the generation of
retrosynthetic matched molecular pairs and analog networks from which distinct
series are isolated. The methodology was applied to systematically extract more
than 17 000 distinct series from the ChEMBL database. For comparison, analog
series were also isolated from screening compounds and drugs. Known biological
activities were mapped to series from ChEMBL, and in more than 13 000 of these
series, key compounds were identified that represented substitution sites of all
analogs within a series and its complete activity profile. The analog series, key
compounds, and activity profiles are made freely available as a resource for
medicinal chemistry applications.
PMID- 27501132
TI - Variance of essential tremor patients' time reproduction deficits.
PMID- 27501133
TI - Understanding Internal Chirality Induction of Triarylsilyl Ethers Formed from
Enantiopure Alcohols.
AB - Chirality transmission from point chirality to helical chirality was explored
using triarylsilyl ethers. Circular dichroism (CD) spectroscopy was employed to
show that the alcohol stereocenter of silylated, enantiopure secondary alcohols
can transmit chirality to the aryl groups on the silicon resulting in a higher
population of one helical conformation over another. Cotton effects
characteristic of the aryl groups organized into one preferred conformation were
observed for all of the compounds examined, which included both triphenyl- and
trinaphthylsilyl groups. Alcohols with an R configuration typically induced a PMP
helical twist, while an S configuration induced a MPM helical twist. Molecular
modeling combined with solid-state structures also gave evidence signifying that
point chirality adjacent to triphenylsilyl groups could bias the conformation of
the phenyl groups. This work helps in our understanding of the origin of
selectivity in our silylation-based kinetic resolutions and a role the phenyl
groups play in that selectivity.
PMID- 27501134
TI - Antiarrhythmic drugs in out-of-hospital cardiac arrest-what does the Amiodarone,
Lidocaine, or Placebo Study tell us?
PMID- 27501135
TI - Effect of Al(3+) co-doping on the luminescence properties of Cu doped Na2SiF6.
AB - Studies were carried out to assess the correlation between thermoluminescence
(TL) and optically stimulated luminescence (OSL) of this phosphor. It was
observed that the OSL and TL glow curve consists of a wide distribution of traps
having different photo-ionization cross-sections, trap depths and frequency
factors. In case of Al doped sample, some of the traps up to 200 degrees C are
assumed to act as a source traps for the observance of OSL due to thermal
transfer of charge carriers into the deep traps beyond 480 degrees C. This
suggests that Al impurities play an important role in the thermal transfer OSL
process. As most of the work on this phenomenon is done on natural materials
(mainly quartz) in which aluminum is a natural impurity, this study will explain
the role of Al in this phenomenon.
PMID- 27501136
TI - Experience in production of (68)Ga-DOTA-NOC for clinical use under an Expanded
Access IND.
AB - [(68)Ga]Ga-DOTA-NOC was produced under an Expanded Access IND for 174 clinical
PET/CT studies to evaluate patients with neuroendocrine tumors. Production
employed either the TiO2-based Eckert & Ziegler (EZAG) (68)Ge/(68)Ga-generator
(with fractionated elution), or the SiO2-based ITG (68)Ge/(68)Ga-generator. In
both cases, [(68)Ga]Ga-DOTA-NOC was reliably produced, without pre-synthesis
purification of the(68)Ga generator eluate, using readily-implemented manual
synthesis procedures. [(68)Ga]Ga-DOTA-NOC radiochemical purity averaged 99.2+/
0.4%. Administered (68)Ga dose averaged 181+/-22 MBq, and administered peptide
mass averaged 43.2+/-5.2ug (n=47) and 23.9+/-5.7ug (n=127), respectively, using
the EZAG and ITG generators. At dose expiration, (68)Ge breakthrough in the final
product averaged 2.7*10(-7)% and 5.4*10(-5%) using the EZAG and ITG generators,
respectively.
PMID- 27501137
TI - Determination of HPGe peak efficiency for voluminous gamma-ray sources by using
an effective solid angle method.
AB - A code called EXVol has been developed to obtain the absolute peak efficiency for
an extended or voluminous gamma-ray source. The method is based on the concept of
effective solid angles. Several efficiency curves that have been determined semi
empirically for voluminous sources are compared with the experimental values
based on certified reference volume sources. To study the geometric and matrix
effects, standard gamma-ray sources of several media, volumes and shapes were
measured using HPGe detectors with three different efficiencies. For the n-type
detector of 32% relative efficiency, the relative deviations are less than +/
10%; this performance is similar to that of existing programs for similar
purposes. The EXVol code is able to calculate the detection efficiency within
approximately five minutes or less. Systematic errors based on EXVol input
parameters, which are mainly due to the inherent uncertainty in the detector's
characteristic dimensions provided by the vendor, are studied to obtain more
accurate specifications of the detectors.
PMID- 27501138
TI - Synthesis and evaluation of a (68)Ga labeled folic acid derivative for targeting
folate receptors.
AB - Present work evaluates the potential of a newly synthesized (68)Ga-NOTA-folic
acid conjugate for PET imaging of tumors over-expressing folate receptors (FRs).
NOTA-folic acid conjugate was synthesized and characterized. It was radiolabeled
with (68)Ga in >= 95% radiolabeling yields. In vitro cell binding studies showed
a maximum cell uptake of 1.7+/-0.4% per million KB cells which was completely
blocked on addition of cold folic acid showing specificity towards the FRs.
However, further studies in tumor xenografts are warranted in order to assess the
potential of (68)Ga-folic acid complex for imaging tumors over-expressing FRs.
PMID- 27501139
TI - Hydroxyapatite (HA) microparticles labeled with (32)P - A promising option in the
radiation synovectomy for inflamed joints.
AB - In the present article we describe a systematic approach pursued for the
synthesis of (32)P-labeled hydroxyapatite (HA) microparticles (1-10um size range)
using no carrier added (NCA) (32)P produced in a nuclear reactor and animal
evaluation of its utility as an expected viable radiopharmaceutical for the
treatment of pain intensive arthrosis. NCA (32)P was produced via the
(32)S(n,p)(32)P route in nuclear reactor with high radionuclidic purity (99.95+/
0.01%, n=5). Phosphorus-32-labeled hydroxyapatite microparticles (1-10um size
range) were synthesized with high radiochemical purity (99.0+/-0.3% n=12) under
optimized conditions and the formulation showed excellent in vitro stability in
saline as well as in rat serum. Intra-articular administration of the
radiolabeled particles in the knee joints of normal Wistar rats showed near
complete retention of activity within the synovial cavity upto 1 month post
administration. The radiochemical formulation thus demonstrated promising
features as a radiopharmaceutical for treatment of arthritis with excellent
logistic advantage for shipment to sites distant from the production facility
thanks to the suitable nuclear decay properties of (32)P.
PMID- 27501140
TI - ADHD and executive functioning deficits in OCD youths who hoard.
AB - Hoarding is common among youth with obsessive compulsive disorder (OCD), with up
to 26% of OCD youth exhibiting hoarding symptoms. Recent evidence from adult
hoarding and OCD cohorts suggests that hoarding symptoms are associated with
executive functioning deficits similar to those observed in subjects with
attention deficit hyperactivity disorder (ADHD). However, while hoarding behavior
often onsets during childhood, there is little information about executive
function deficits and ADHD in affected children and adolescents. The study sample
included 431 youths (ages 6-17 years) diagnosed with OCD who participated in the
OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association
Study and completed a series of clinician-administered and parent report
assessments, including diagnostic interviews and measures of executive
functioning (Behavior Rating Inventory of Executive Functioning; BRIEF) and
hoarding severity (Hoarding Rating Scale-Interview; HRS-I). 113 youths (26%) had
clinically significant levels of hoarding compulsions. Youths with and without
hoarding differed significantly on most executive functioning subdomains and
composite indices as measured by the parent-rated BRIEF. Groups did not differ in
the frequency of full DSM-IV ADHD diagnoses; however, the hoarding group had
significantly greater number of inattention and hyperactivity symptoms compared
to the non-hoarding group. In multivariate models, we found that overall BRIEF
scores were related to hoarding severity, adjusting for age, gender and ADHD
symptoms. These findings suggest an association between hoarding and executive
functioning deficits in youths with OCD, and assessing executive functioning may
be important for investigating the etiology and treatment of children and
adolescents with hoarding and OCD.
PMID- 27501141
TI - A population study of the association between sleep disturbance and suicidal
behaviour in people with mental illness.
AB - Limited representative research has considered the relationship between sleep
disturbance and suicidal behaviour among people with mental illness. We
investigated the relationship between sleep disturbance and suicidal behaviour
across Part II interview of the National Comorbidity Survey Replication (NCSR).
The associations between sleep disturbance and suicidal behaviour (thoughts,
plans and attempts) were investigated using logistic and multinomial logistic
regressions and stratified across six mental disorder groups (depression,
anxiety, substance use disorders (SUD), eating disorders (ED), bipolar disorders
(BD) and early life disorders). From 5701 participants (mean age 43.4 years 58%
women), people with any mental disorder experiencing sleep disturbance were at
increased odds of suicidal thoughts (odds ratio (OR): 2.5; 95% CI: 1.7, 3.6) and
suicidal plans and attempts (OR: 5.7; 95% CI: 2.7, 11.9) adjusting for age, sex
and income. People with BD (OR: 8.9; 95 CI: 2.1, 38.1), early life disorders (OR
6.98, 95% ci 2.48, 19.67), depression (OR 1.88, 95% CI 1.14, 3.11), anxiety (OR
1.90, 95% CI 1.28, 2.85) and SUD (2.60, 95% CI 1.23, 5.49) but not ED, were at
increased odds of suicidal thoughts in the presence of sleep disturbance.
Adjusting for anti-depressant intake attenuated the effect sizes by up to 20% but
the associations remained significant. In conclusion, sleep disturbance is a
potential risk factor for suicidal behaviours in people with mental illness.
Monitoring and management of sleep disturbance in clinical practice might be an
important strategy to mitigate suicidal behaviours in people with mental illness.
PMID- 27501142
TI - Road accidents and business cycles in Spain.
AB - This paper explores the causes behind the downturn in road accidents in Spain
across the last decade. Possible causes are grouped into three categories:
Institutional factors (a Penalty Point System, PPS, dating from 2006),
technological factors (active safety and passive safety of vehicles), and
macroeconomic factors (the Great recession starting in 2008, and an increase in
fuel prices during the spring of 2008). The PPS has been blessed by incumbent
authorities as responsible for the decline of road fatalities in Spain. Using
cointegration techniques, the GDP growth rate, the fuel price, the PPS, and
technological items embedded in motor vehicles appear to be statistically
significantly related with accidents. Importantly, PPS is found to be significant
in reducing fatal accidents. However, PPS is not significant for non-fatal
accidents. In view of these results, we conclude that road accidents in Spain are
very sensitive to the business cycle, and that the PPS influenced the severity
(fatality) rather than the quantity of accidents in Spain. Importantly,
technological items help explain a sizable fraction in accidents downturn, their
effects dating back from the end of the nineties.
PMID- 27501143
TI - Assessment of Methods for the Intracellular Blockade of GABAA Receptors.
AB - Selective blockade of inhibitory synaptic transmission onto specific neurons is a
useful tool for dissecting the excitatory and inhibitory synaptic components of
ongoing network activity. To achieve this, intracellular recording with a patch
solution capable of blocking GABAA receptors has advantages over other
manipulations, such as pharmacological application of GABAergic antagonists or
optogenetic inhibition of populations of interneurones, in that the majority of
inhibitory transmission is unaffected and hence the remaining network activity
preserved. Here, we assess three previously described methods to block
inhibition: intracellular application of the molecules picrotoxin, 4,4'-dinitro
stilbene-2,2'-disulphonic acid (DNDS) and 4,4'-diisothiocyanostilbene-2,2'
disulphonic acid (DIDS). DNDS and picrotoxin were both found to be ineffective at
blocking evoked, monosynaptic inhibitory postsynaptic currents (IPSCs) onto mouse
CA1 pyramidal cells. An intracellular solution containing DIDS and caesium
fluoride, but lacking nucleotides ATP and GTP, was effective at decreasing the
amplitude of IPSCs. However, this effect was found to be independent of DIDS, and
the absence of intracellular nucleotides, and was instead due to the presence of
fluoride ions in this intracellular solution, which also blocked spontaneously
occurring IPSCs during hippocampal sharp waves. Critically, intracellular
fluoride ions also caused a decrease in both spontaneous and evoked excitatory
synaptic currents and precluded the inclusion of nucleotides in the intracellular
solution. Therefore, of the methods tested, only fluoride ions were effective for
intracellular blockade of IPSCs but this approach has additional cellular effects
reducing its selectivity and utility.
PMID- 27501144
TI - Survey and Experimental Infection of Enteropathogenic Escherichia coli in Common
Marmosets (Callithrix jacchus).
AB - Common marmosets (Callithrix jacchus) are frequently used for biomedical research
but can be afflicted with diarrhea-a serious and potentially lethal health
problem. Enteropathogenic Escherichia coli (EPEC) is thought to be the causative
pathogen of hemorrhagic typhlocolitis in common marmosets, but the actual
incidence of the disease and the relationship between EPEC and hematochezia are
unknown. This study investigated the prevalence of EPEC infection in common
marmosets and the association between EPEC and hematochezia. A total of 230 stool
or rectal swab samples were collected from 230 common marmosets (98 clinically
healthy, 85 diarrhea, and 47 bloody stool samples) and tested by culture-based
detection and PCR amplification of VT1, VT2, LT, ST, eae, and bfp genes. Healthy
animals were divided into three groups (n = 4 each for high and low concentration
groups and n = 2 as negative control), and those in the experimental groups were
perorally inoculated with a 2-ml of suspension of EPEC R811 strain adjusted to 5
* 108 (high concentration) and 5 * 104 (low concentration) CFU/ ml. Two animals
in each group were examined 3 and 14 days post-inoculation (DPI). EPEC was
detected in 10 of 98 clinically healthy samples (10.2%), 17 of 85 diarrhea
samples (20%), and all 47 bloody stool samples (100%), with a significant
difference detected between presence of EPEC and sample status (P < 0.01). Acute
hematochezia was observed in all animals of the high-concentration group but not
in other groups at 1 or 2 DPI. A histopathological examination revealed the
attachment of gram-negative bacilli to epithelial apical membranes and
desquamated epithelial cells in the cecum of animals in the high-concentration
group at 3 DPI. These findings suggest that EPEC is a causative agent of
hemorrhagic typhlocolitis in common marmosets.
PMID- 27501145
TI - Differential Assembly of Catalytic Interactions within the Conserved Active Sites
of Two Ribozymes.
AB - Molecular recognition is central to biology and a critical aspect of RNA
function. Yet structured RNAs typically lack the preorganization needed for
strong binding and precise positioning. A striking example is the group I
ribozyme from Tetrahymena, which binds its guanosine substrate (G) orders of
magnitude slower than diffusion. Binding of G is also thermodynamically coupled
to binding of the oligonucleotide substrate (S) and further work has shown that
the transition from E*G to E*S*G accompanies a conformational change that allows
G to make the active site interactions required for catalysis. The group I
ribozyme from Azoarcus has a similarly slow association rate but lacks the
coupled binding observed for the Tetrahymena ribozyme. Here we test, using G
analogs and metal ion rescue experiments, whether this absence of coupling arises
from a higher degree of preorganization within the Azoarcus active site. Our
results suggest that the Azoarcus ribozyme forms cognate catalytic metal ion
interactions with G in the E*G complex, interactions that are absent in the
Tetrahymena E*G complex. Thus, RNAs that share highly similar active site
architectures and catalyze the same reactions can differ in the assembly of
transition state interactions. More generally, an ability to readily access
distinct local conformational states may have facilitated the evolutionary
exploration needed to attain RNA machines that carry out complex, multi-step
processes.
PMID- 27501146
TI - Calculation of the Average Cost per Case of Dengue Fever in Mexico Using a Micro
Costing Approach.
AB - INTRODUCTION: The increasing burden of dengue fever (DF) in the Americas, and the
current epidemic in previously unaffected countries, generate major costs for
national healthcare systems. There is a need to quantify the average cost per DF
case. In Mexico, few data are available on costs, despite DF being endemic in
some areas. Extrapolations from studies in other countries may prove unreliable
and are complicated by the two main Mexican healthcare systems (the Secretariat
of Health [SS] and the Mexican Social Security Institute [IMSS]). The present
study aimed to generate specific average DF cost-per-case data for Mexico using a
micro-costing approach. METHODS: Expected medical costs associated with an ideal
management protocol for DF (denoted 'ideal costs') were compared with the medical
costs of current treatment practice (denoted 'real costs') in 2012. Real cost
data were derived from chart review of DF cases and interviews with patients and
key personnel from 64 selected hospitals and ambulatory care units in 16 states
for IMSS and SS. In both institutions, ideal and real costs were estimated using
the program, actions, activities, tasks, inputs (PAATI) approach, a micro-costing
technique developed by us. RESULTS: Clinical pathways were obtained for 1,168
patients following review of 1,293 charts. Ideal and real costs for SS patients
were US$165.72 and US$32.60, respectively, in the outpatient setting, and
US$587.77 and US$490.93, respectively, in the hospital setting. For IMSS
patients, ideal and real costs were US$337.50 and US$92.03, respectively, in the
outpatient setting, and US$2,042.54 and US$1,644.69 in the hospital setting.
CONCLUSIONS: The markedly higher ideal versus real costs may indicate
deficiencies in the actual care of patients with DF. It may be necessary to
derive better estimates with micro-costing techniques and compare the ideal
protocol with current practice when calculating these costs, as patients do not
always receive optimal care.
PMID- 27501147
TI - Let's twist again: elasto-capillary assembly of parallel ribbons.
AB - We show the self-assembly through twisting and bending of side by side ribbons
under the action of capillary forces. Micro-ribbons made of silicon nitride are
batch assembled at the wafer scale. We study their assembly as a function of
their dimensions and separating distance. Model experiments are carried out at
the macroscopic scale where the tension in ribbons can easily be tuned. The
process is modeled considering the competition between capillary, elastic and
tension forces. Theory shows a good agreement for macroscale assemblies, while
the accuracy is within 30% at the micrometer scale. This simple self-assembly
technique yields highly symmetric and controllable structures which could be used
for batch fabrication of functional 3D micro-structures.
PMID- 27501148
TI - Inter-Annual Variability of Area-Scaled Gaseous Carbon Emissions from Wetland
Soils in the Liaohe Delta, China.
AB - Global management of wetlands to suppress greenhouse gas (GHG) emissions,
facilitate carbon (C) sequestration, and reduce atmospheric CO2 concentrations
while simultaneously promoting agricultural gains is paramount. However, studies
that relate variability in CO2 and CH4 emissions at large spatial scales are
limited. We investigated three-year emissions of soil CO2 and CH4 from the
primary wetland types of the Liaohe Delta, China, by focusing on a total wetland
area of 3287 km2. One percent is Suaeda salsa, 24% is Phragmites australis, and
75% is rice. While S. salsa wetlands are under somewhat natural tidal influence,
P. australis and rice are managed hydrologically for paper and food,
respectively. Total C emissions from CO2 and CH4 from these wetland soils were
2.9 Tg C/year, ranging from 2.5 to 3.3 Tg C/year depending on the year assessed.
Primary emissions were from CO2 (~98%). Photosynthetic uptake of CO2 would
mitigate most of the soil CO2 emissions, but CH4 emissions would persist.
Overall, CH4 fluxes were high when soil temperatures were >18 degrees C and pore
water salinity <18 PSU. CH4 emissions from rice habitat alone in the Liaohe Delta
represent 0.2% of CH4 carbon emissions globally from rice. With such a large area
and interannual sensitivity in soil GHG fluxes, management practices in the Delta
and similar wetlands around the world have the potential not only to influence
local C budgeting, but also to influence global biogeochemical cycling.
PMID- 27501149
TI - Minnelide/Triptolide Impairs Mitochondrial Function by Regulating SIRT3 in P53
Dependent Manner in Non-Small Cell Lung Cancer.
AB - Minnelide/Triptolide (TL) has recently emerged as a potent anticancer drug in non
small cell lung cancer (NSCLC). However, the precise mechanism of its action
remains ambiguous. In this study, we elucidated the molecular basis for TL
induced cell death in context to p53 status. Cell death was attributed to
dysfunction of mitochondrial bioenergetics in p53-deficient cells, which was
characterized by decreased mitochondrial respiration, steady-state ATP level and
membrane potential, but augmented reactive oxygen species (ROS). Increased ROS
production resulted in oxidative stress in TL-treated cells. This was exhibited
by elevated nuclear levels of a redox-sensitive transcriptional factor, NF-E2
related factor-2 (NRF2), along with diminished cellular glutathione (GSH)
content. We further demonstrated that in the absence of p53, TL blunted the
expression of mitochondrial SIRT3 triggering increased acetylation of NDUAF9 and
succinate dehydrogenase, components of complexes I and II of the electron
transport chain (ETC). TL-mediated hyperacetylation of complexes I and II
proteins and these complexes displayed decreased enzymatic activities. We also
provide the evidence that P53 regulate steady-state level of SIRT3 through
Proteasome-Pathway. Finally, forced overexpression of Sirt3, but not deacetylase
deficient mutant of Sirt3 (H243Y), restored the deleterious effect of TL on p53
deficient cells by rescuing mitochondrial bioenergetics. On contrary, Sirt3
deficiency in the background of wild-type p53 triggered TL-induced mitochondrial
impairment that echoed TL effect in p53-deficeint cells. These findings
illustrate a novel mechanism by which TL exerts its potent effects on
mitochondrial function and ultimately the viability of NSCLC tumor.
PMID- 27501150
TI - Molecular modifiers reveal a mechanism of pathological crystal growth inhibition.
AB - Crystalline materials are crucial to the function of living organisms, in the
shells of molluscs, the matrix of bone, the teeth of sea urchins, and the
exoskeletons of coccoliths. However, pathological biomineralization can be an
undesirable crystallization process associated with human diseases. The crystal
growth of biogenic, natural and synthetic materials may be regulated by the
action of modifiers, most commonly inhibitors, which range from small ions and
molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and
impede the addition of solute, thereby reducing the rate of growth. Complex
inhibitor-crystal interactions in biomineralization are often not well
elucidated. Here we show that two molecular inhibitors of calcium oxalate
monohydrate crystallization--citrate and hydroxycitrate--exhibit a mechanism that
differs from classical theory in that inhibitor adsorption on crystal surfaces
induces dissolution of the crystal under specific conditions rather than a
reduced rate of crystal growth. This phenomenon occurs even in supersaturated
solutions where inhibitor concentration is three orders of magnitude less than
that of the solute. The results of bulk crystallization, in situ atomic force
microscopy, and density functional theory studies are qualitatively consistent
with a hypothesis that inhibitor-crystal interactions impart localized strain to
the crystal lattice and that oxalate and calcium ions are released into solution
to alleviate this strain. Calcium oxalate monohydrate is the principal component
of human kidney stones and citrate is an often-used therapy, but hydroxycitrate
is not. For hydroxycitrate to function as a kidney stone treatment, it must be
excreted in urine. We report that hydroxycitrate ingested by non-stone-forming
humans at an often-recommended dose leads to substantial urinary excretion. In
vitro assays using human urine reveal that the molecular modifier hydroxycitrate
is as effective an inhibitor of nucleation of calcium oxalate monohydrate
nucleation as is citrate. Our findings support exploration of the clinical
potential of hydroxycitrate as an alternative treatment to citrate for kidney
stones.
PMID- 27501151
TI - Structural basis for the antifolding activity of a molecular chaperone.
AB - Molecular chaperones act on non-native proteins in the cell to prevent their
aggregation, premature folding or misfolding. Different chaperones often exert
distinct effects, such as acceleration or delay of folding, on client proteins
via mechanisms that are poorly understood. Here we report the solution structure
of SecB, a chaperone that exhibits strong antifolding activity, in complex with
alkaline phosphatase and maltose-binding protein captured in their unfolded
states. SecB uses long hydrophobic grooves that run around its disk-like shape to
recognize and bind to multiple hydrophobic segments across the length of non
native proteins. The multivalent binding mode results in proteins wrapping around
SecB. This unique complex architecture alters the kinetics of protein binding to
SecB and confers strong antifolding activity on the chaperone. The data show how
the different architectures of chaperones result in distinct binding modes with
non-native proteins that ultimately define the activity of the chaperone.
PMID- 27501152
TI - The prion protein is an agonistic ligand of the G protein-coupled receptor
Adgrg6.
AB - Ablation of the cellular prion protein PrP(C) leads to a chronic demyelinating
polyneuropathy affecting Schwann cells. Neuron-restricted expression of PrP(C)
prevents the disease, suggesting that PrP(C) acts in trans through an
unidentified Schwann cell receptor. Here we show that the cAMP concentration in
sciatic nerves from PrP(C)-deficient mice is reduced, suggesting that PrP(C) acts
via a G protein-coupled receptor (GPCR). The amino-terminal flexible tail
(residues 23-120) of PrP(C) triggered a concentration-dependent increase in cAMP
in primary Schwann cells, in the Schwann cell line SW10, and in HEK293T cells
overexpressing the GPCR Adgrg6 (also known as Gpr126). By contrast, naive HEK293T
cells and HEK293T cells expressing several other GPCRs did not react to the
flexible tail, and ablation of Gpr126 from SW10 cells abolished the flexible tail
induced cAMP response. The flexible tail contains a polycationic cluster
(KKRPKPG) similar to the GPRGKPG motif of the Gpr126 agonist type-IV collagen. A
KKRPKPG-containing PrPC-derived peptide (FT(23-50)) sufficed to induce a Gpr126
dependent cAMP response in cells and mice, and improved myelination in
hypomorphic gpr126 mutant zebrafish (Danio rerio). Substitution of the cationic
residues with alanines abolished the biological activity of both FT(23-50) and
the equivalent type-IV collagen peptide. We conclude that PrP(C) promotes myelin
homeostasis through flexible tail-mediated Gpr126 agonism. As well as clarifying
the physiological role of PrP(C), these observations are relevant to the
pathogenesis of demyelinating polyneuropathies--common debilitating diseases for
which there are limited therapeutic options.
PMID- 27501154
TI - Faecal pollution along the southeastern coast of Florida and insight into the use
of pepper mild mottle virus as an indicator.
AB - AIMS: To identify faecal pollution along the southeastern Florida coast and
determine the performance of a reverse transcription-quantitative polymerase
chain reaction (RT-qPCR) method for pepper mild mottle virus (PMMoV). METHODS AND
RESULTS: In 2014, bimonthly surface water samples were collected from inlets,
exposed to runoff and septic seepage, and coastal sites, exposed to ocean
outfalls. Analysis of culturable enterococci and a suite of microbial source
tracking (MST) markers (BacHum, CowM2, DogBact, HF183, HPyV, PMMoV) revealed
faecal pollution, primarily of human origin, at all sites. Since PMMoV was
detected more frequently than other MST markers, the process limits of
quantification (undiluted to 10-2 dilution) and detection (10-2 dilution) for the
RT-qPCR method were determined by seeding untreated wastewater into the coastal
waters. Simulated quantitative microbial risk assessment, employing human
norovirus as a reference pathogen, calculated a 0.286 median risk of
gastrointestinal illness associated with the PMMoV limit of detection.
CONCLUSIONS: All sites met the U.S. EPA recreational water criteria, despite
detection of domestic wastewater-associated MST markers. PMMoV correlated only
with human-associated MST markers. SIGNIFICANCE AND IMPACT OF THE STUDY: This
study demonstrated that PMMoV is an important domestic wastewater-associated
marker that should be included in the MST toolbox; therefore, future studies
should thoroughly investigate the health risks associated with its detection and
quantification in environmental waters.
PMID- 27501153
TI - Mitochondria-specific antioxidant supplementation does not influence endurance
exercise training-induced adaptations in circulating angiogenic cells, skeletal
muscle oxidative capacity or maximal oxygen uptake.
AB - KEY POINTS: Reducing excessive oxidative stress, through chronic exercise or
antioxidants, can decrease the negative effects induced by excessive amounts of
oxidative stress. Transient increases in oxidative stress produced during acute
exercise facilitate beneficial vascular training adaptations, but the effects of
non-specific antioxidants on exercise training-induced vascular adaptations
remain elusive. Circulating angiogenic cells (CACs) are an exercise-inducible
subset of white blood cells that maintain vascular integrity. We investigated
whether mitochondria-specific antioxidant (MitoQ) supplementation would affect
the response to 3 weeks of endurance exercise training in CACs, muscle
mitochondrial capacity and maximal oxygen uptake in young healthy men. We show
that endurance exercise training increases multiple CAC types, an adaptation that
is not altered by MitoQ supplementation. Additionally, MitoQ does not affect
skeletal muscle or whole-body aerobic adaptations to exercise training. These
results indicate that MitoQ supplementation neither enhances nor attenuates
endurance training adaptations in young healthy men. ABSTRACT: Antioxidants have
been shown to improve endothelial function and cardiovascular outcomes. However,
the effects of antioxidants on exercise training-induced vascular adaptations
remain elusive. General acting antioxidants combined with exercise have not
impacted circulating angiogenic cells (CACs). We investigated whether
mitochondria-specific antioxidant (MitoQ) supplementation would affect the
response to 3 weeks of endurance exercise training on CD3+ , CD3+ /CD31+ , CD14+
/CD31+ , CD31+ , CD34+ /VEGFR2+ and CD62E+ peripheral blood mononuclear cells
(PBMCs), muscle mitochondrial capacity, and maximal oxygen uptake (VO2 max ) in
healthy men aged 22.1 +/- 0.7 years, with a body mass index of 26.9 +/- 0.9 kg m
2 , and 24.8 +/- 1.3% body fat. Analysis of main effects revealed that training
induced 33, 105 and 285% increases in CD14+ /CD31+ , CD62E+ and CD34+ /VEGFR2+
CACs, respectively, and reduced CD3+ /CD31- PBMCs by 14%. There was no effect of
MitoQ on CAC levels. Also independent of MitoQ supplementation, exercise training
significantly increased quadriceps muscle mitochondrial capacity by 24% and VO2
max by roughly 7%. In conclusion, endurance exercise training induced increases
in multiple CAC types, and this adaptation is not modified by MitoQ
supplementation. Furthermore, we demonstrate that a mitochondrial-targeted
antioxidant does not influence skeletal muscle or whole-body aerobic adaptations
to exercise training.
PMID- 27501155
TI - Cognitive decline in the elderly after surgery and anaesthesia: results from the
Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort.
AB - Concerns have been raised about the effects on cognition of anaesthesia for
surgery, especially in elderly people. We recorded cognitive decline in a cohort
of 394 people (198 women) with median (IQR) age at recruitment of 72.6 (66.6
77.8) years, of whom 109 had moderate or major surgery during a median (IQR)
follow-up of 4.1 (2.0-7.6) years. Cognitive decline was more rapid in people who
on recruitment were: older, p = 0.0003; male, p = 0.027; had worse cognition, p <
0.0001; or carried the epsilon4 allele of apoliprotein E (APOEepsilon4), p =
0.008; and after an operation if cognitive impairment was already diagnosed, p =
0.0001. Cognitive decline appears to accelerate after surgery in elderly patients
diagnosed with cognitive impairment, but not other elderly patients.
PMID- 27501156
TI - Genetics of human origin and evolution: high-altitude adaptations.
AB - High altitude, defined as elevations lying above 2500m sea level, challenges
human survival and reproduction. This environment provides a natural experimental
design wherein specific populations, Andeans, Ethiopians, and Tibetans, have
lived in a chronic hypoxia state for millennia. These human groups have overcome
the low ambient oxygen tension of high elevation via unique physiologic and
genetic adaptations. Genomic studies have identified several genes that underlie
high-altitude adaptive phenotypes, many of which are central components of the
Hypoxia Inducible Factor (HIF) pathway. Further study of mechanisms governing the
adaptive changes responsible for high-altitude adaptation will contribute to our
understanding of the molecular basis of evolutionary change and assist in the
functional annotation of the human genome.
PMID- 27501157
TI - Antibacterial nanohydroxyapatite/polyurethane composite scaffolds with silver
phosphate particles for bone regeneration.
AB - Solving the issue of infection associated with implanted bone substitutes is one
of the modern challenges of the biomedical engineering field. The purpose of this
study was to develop a novel porous scaffold with sufficient antibacterial
activity for bone repair or regeneration. Porous nanohydroxyapatite/polyurethane
(n-HA/PU) composite scaffolds containing different amounts of silver phosphate
particles were prepared through the in situ foaming method. Subsequently, their
physicochemical properties, antibacterial abilities, and preliminary
cytocompatibilities were evaluated. The results indicated that the porosity and
mechanical properties of the n-HA/PU scaffolds incorporated with Ag3PO4 did not
change significantly compared to n-HA/PU scaffold without Ag3PO4. The release of
Ag(+) was time and concentration dependent, increasing with the immersion time
and Ag3PO4 percentage in the scaffolds. A continuous Ag(+) release can last more
than 3 weeks. The antibacterial tests and cytocompatibility evaluation revealed
that n-HA/PU scaffolds with 3 wt% Ag3PO4 (n-HA/PU3) exhibit stronger
antimicrobial effects as well as satisfactory cytocompatibility. The n-HA/PU3
scaffolds may hold great potential for application in the field of bone
regeneration, especially for infection-associated bone defect repair.
PMID- 27501158
TI - Comparison of drug dissolution profiles: a proposal based on tolerance limits.
AB - Meaningful comparison of the dissolution profiles between the reference and test
formulations of a drug is critical for assessing similarity between the two
formulations, and for quality control purposes. Such a dissolution profile
comparison is required by regulatory authorities, and the criteria used for this
include the widely used difference factor f1 and a similarity factor f2 ,
recommended by the Food and Drug Administration . In spite of their extensive use
in practice, the two factors have been heavily criticized on various grounds; the
criticisms include ignoring sampling variability and ignoring the correlations
across time points while using the criteria in practice. The goal of this article
is to put f1 and f2 on a firm statistical footing by developing tolerance limits
for the distributions of f1 and f2 , so that both the sampling variability and
the correlations over time points are taken into account. Because f1 and f2 are
defined in terms of sample mean dissolution profiles, they are not appropriate
for comparing individual dissolution profiles. For the latter, we have considered
similar criteria and have derived tolerance limits. Both parametric and
nonparametric approaches are explored, and a bootstrap calibration is used to
improve accuracy of the tolerance limits. Simulated coverage probabilities show
that the method leads to accurate tolerance limits. Two examples are used to
illustrate the methodology. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501159
TI - Effects of JTV-519 on stretch-induced manifestations of mechanoelectric feedback.
AB - JTV-519 is a 1,4-benzothiazepine derivative with multichannel effects that
inhibits Ca2+ release from the sarcoplasmic reticulum and stabilizes the closed
state of the ryanodine receptor, preventing myocardial damage and the induction
of arrhythmias during Ca2+ overload. Mechanical stretch increases cellular Na+
inflow, activates the reverse mode of the Na+ /Ca2+ exchanger, and modifies Ca2+
handling and myocardial electrophysiology, favoring arrhythmogenesis. This study
aims to determine whether JTV-519 modifies the stretch-induced manifestations of
mechanoelectric feedback. The ventricular fibrillation (VF) modifications induced
by acute stretch were studied in Langendorff-perfused rabbit hearts using
epicardial multiple electrodes under control conditions (n=9) or during JTV-519
perfusion: 0.1 MUmol/L (n=9) and 1 MUmol/L (n=9). Spectral and mapping techniques
were used to establish the baseline, stretch and post-stretch VF characteristics.
JTV-519 slowed baseline VF and decreased activation complexity. These effects
were dose-dependent (baseline VF dominant frequency: control=13.9+/-2.2 Hz; JTV
0.1 MUmol/L=11.1+/-1.1 Hz, P<.01; JTV 1 MUmol/L=6.6+/-1.1 Hz, P<.0001). The
stretch-induced acceleration of VF (control=38.8%) was significantly reduced by
JTV-519 0.1 MUmol/L (19.8%) and abolished by JTV 1 MUmol/L (-1.5%). During
stretch, the VF activation complexity index was reduced in both JTV-519 series
(control=1.60+/-0.15; JTV 0.1 MUmol/L=1.13+/-0.3, P<.0001; JTV 1 MUmol/L=0.57+/
0.21, P<.0001), and was independently related to VF dominant frequency (R=.82;
P<.0001). The fifth percentile of the VF activation intervals, conduction
velocity and wavelength entered the multiple linear regression model using
dominant frequency as the dependent variable (R=-.84; P<.0001). In conclusion,
JTV-519 slowed and simplified the baseline VF activation patterns and abolished
the stretch-induced manifestations of mechanoelectric feedback.
PMID- 27501160
TI - Effectiveness of community-based exercise intervention programme in obese adults
with metabolic syndrome.
AB - AIMS AND OBJECTIVES: The objective of this study was to change the
anthropometric, clinical, biochemical indicators and the rate of metabolic
syndrome among obese adults in community. BACKGROUND: Obesity is an indicator of
metabolic syndrome and cardiometabolic diseases. Obesity increases national
health care expenditure in Taiwan. The high prevalence of obesity is not only a
public health issue but also an economic problem. Changes in lifestyle can help
to prevent metabolic syndrome for individuals with obesity. DESIGN: A randomised
controlled trial was applied. METHODS: In this randomised controlled trial by
location, 136 metabolically abnormal obese individuals were included. The related
indicators with metabolic syndrome were measured at baseline and after six
months. The experimental group participated in a six-month community-based
programme including provided exercise environments, exercise skills and
volunteers' reminding. The control group was only provided environment and
skills. RESULTS: One hundred and thirty-one participants completed this trail. In
comparison with the baseline, the intervention group showed a significant
increase in high-density lipoprotein cholesterol (2.34 mg/dl), and decrease in
body weight (1.09 kg), waist circumference (3.63 cm), systolic blood pressure
(10.52 mmHg), diastolic blood pressure (5.21 mmHg), fasting blood glucose (5.84
mg/dl) and body mass index (0.74 kg/m(2) ). In the control group, significant
decrease in body mass index and waist circumference were discovered. Compared to
the changes between the two groups, the results showed there were significant
differences in waist circumference, systolic blood pressure, diastolic blood
pressure and high-density lipoprotein cholesterol. CONCLUSIONS: The community
based intervention could help to improve high-density lipoprotein cholesterol,
reduce body weight, body mass index, waist circumference, blood pressure and
fasting blood glucose in metabolically abnormal obese. RELEVANCE TO CLINICAL
PRACTICE: This community-based programme helped metabolically abnormal obese
individuals become metabolically healthy. In the future, community nurses will
work with village heads and volunteers. They can encourage residents in the
communities to have healthy lifestyle. As a result, the goal of this programme
will be successfully achieved with less time and effort.
PMID- 27501161
TI - Childhood urinary tract infection caused by extended-spectrum beta-lactamase
producing bacteria: Risk factors and empiric therapy.
AB - BACKGROUND: This study investigated risk factors of childhood urinary tract
infection (UTI) associated with extended-spectrum beta-lactamase (ESBL)-producing
bacteria (ESBL-positive UTI) and evaluated antimicrobial resistance as well as
empiric treatment of childhood UTI. METHODS: The records of children with
positive urine culture between 1 January 2008 and 31 December 2012 were
evaluated. Patients with positive urine culture for ESBL-producing bacteria were
defined as the ESBL-positive group, whereas patients of the same gender and
similar age with positive urine culture for non-ESBL-producing bacteria were
defined as the ESBL-negative group. Each ESBL-positive patient was matched with
two ESBL-negative patients. RESULTS: The ESBL-positive and negative groups
consisted of 154 and 308 patients, respectively. Potential risk factors for ESBL
positive UTI were identified as presence of underlying disease, clean
intermittent catheterization (CIC), hospitalization, use of any antibiotic and
history of infection in the last 3 months (P < 0.05). On logistic regression
analysis, CIC, hospitalization and history of infection in the last 3 months were
identified as independent risk factors. In the present study, 324 of 462 patients
had empiric therapy. Empiric therapy was inappropriate in 90.3% of the ESBL
positive group and in 4.5% of the ESBL-negative group. Resistance to
nitrofurantoin was similar between groups (5.1% vs 1.2%, P = 0.072); resistance
to amikacin was low in the ESBL-positive group (2.6%) and there was no resistance
in the ESBL-negative group. CONCLUSIONS: Clean intermittent catheterization,
hospitalization and history of infection in the last 3 months should be
considered as risk factors for ESBL-positive UTI. The combination of ampicillin
plus amikacin should be taken into consideration for empiric therapy in patients
with acute pyelonephritis who have the risk factors for ESBL-positive UTI.
Nitrofurantoin seems to be a logical choice for the empiric therapy of cystitis.
PMID- 27501162
TI - Organizational justice and disability pension from all-causes, depression and
musculoskeletal diseases: A Finnish cohort study of public sector employees.
AB - OBJECTIVES: Work-related stress has been linked to increased risk of disability
pensioning, but the association between perceived justice of managerial behavior
and decision-making processes at the workplace (ie, organizational justice) and
risk of disability pensioning remains unknown. We examined the associations of
organizational justice and its relational and procedural components with all
cause and diagnosis-specific disability pensions with repeated measures of
justice. METHODS: Data from 24 895 employees responding to repeated surveys on
organizational justice in 2000-2002 and 2004 were linked to the records of a
national register for disability pensions from 2005-2011. Associations of long
term organizational justice (average score from two surveys) with disability
pensions were studied with Cox proportional hazard regression adjusted for
demographics, socioeconomic status, baseline health and health risk behavior,
stratified by sex. RESULTS: During a mean follow-up of 6.4 years, 1658 (7%)
employees were granted disability pension (282 due to depression; 816 due to
musculoskeletal diseases). Higher organizational justice was associated with a
lower risk of disability pensioning [hazard ratio (HR) per one-unit increase in 5
point justice scale 0.87 (95% CI 0.81-0.94)]. For disability pension due to
depression and musculoskeletal diseases, the corresponding HR were 0.77 (95% CI
0.65-0.91) and 0.87 (95% CI 0.79-0.97), respectively. Adjustment for job strain
and effort-reward imbalance attenuated the HR by 20-80%. CONCLUSIONS:
Supervisors' fair treatment of employees and fair decision-making in the
organizations are associated with a decreased risk of disability pensioning from
all-causes, depression and musculoskeletal diseases. These associations may be
attributable to a wider range of favorable work characteristics.
PMID- 27501163
TI - Sexism within anatomy as perceived by professional anatomists and in comparison
with the perceptions of medical students.
AB - Two hundred and eight professional anatomists responded to a questionnaire
inviting them to address the possibility that social/gender factors hinder the
dispassionate representation of anatomy. Ethical approval for the study was
obtained from Cardiff University. The results of the survey provided comparisons
with the attitudes of medical students that have previously been reported (Morgan
et al., 2014). Although a few differences were discerned between females and
males in our surveys and between anatomists and medical students, overall our
findings suggest that, while both professional anatomists and medical students
recognize the importance of gender issues and do not wish to associate with
sexism, most are unaware of the possible negative aspects of sexism within
anatomy. We recommend that teachers of anatomy should become more aware of the
possibility of adverse effects on professional matters relating to equality and
diversity issues. Clin. Anat. 29:892-910, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27501164
TI - Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine
Density in Primary Hippocampal Neuron Cultures.
AB - The zinc metallopeptidase insulin regulated aminopeptidase (IRAP), which is
highly expressed in the hippocampus and other brain regions associated with
cognitive function, has been identified as a high-affinity binding site of the
hexapeptide angiotensin IV (Ang IV). This hexapeptide is thought to facilitate
learning and memory by binding to the catalytic site of IRAP to inhibit its
enzymatic activity. In support of this hypothesis, low molecular weight,
nonpeptide specific inhibitors of IRAP have been shown to enhance memory in
rodent models. Recently, it was demonstrated that linear and macrocyclic Ang IV
derived peptides can alter the shape and increase the number of dendritic spines
in hippocampal cultures, properties associated with enhanced cognitive
performance. After screening a library of 10 500 drug-like substances for their
ability to inhibit IRAP, we identified a series of low molecular weight aryl
sulfonamides, which exhibit no structural similarity to Ang IV, as moderately
potent IRAP inhibitors. A structural and biological characterization of three of
these aryl sulfonamides was performed. Their binding modes to human IRAP were
explored by docking calculations combined with molecular dynamics simulations and
binding affinity estimations using the linear interaction energy method. Two
alternative binding modes emerged from this analysis, both of which correctly
rank the ligands according to their experimental binding affinities for this
series of compounds. Finally, we show that two of these drug-like IRAP inhibitors
can alter dendritic spine morphology and increase spine density in primary
cultures of hippocampal neurons.
PMID- 27501165
TI - My Sister Myself: A Controlled Study of the Relationship Between Women with a
Lifetime Diagnosis of Anorexia Nervosa and Their Sisters.
AB - This study focused on the quality of the relationship between women with a
lifetime anorexia nervosa (AN) diagnosis and their sisters, in the context of
family functioning. Participants were 112 sister pairs including a woman with a
lifetime diagnosis of AN, and 356 sister pairs with no history of an eating
disorder. Participants completed the Sibling Relationship Questionnaire, Family
Environment Scale and Eating Attitudes Test-26. We hypothesised that sister
relationships would be less favourably assessed by women with an AN diagnosis
than by their sisters, and less favourably assessed overall in the AN sister
pairs than in the healthy sib-pair controls. These hypotheses were confirmed.
Also, the AN sisters viewed the family as less cohesive and more conflicted than
their non-affected sisters. For the AN sisters, there was an inverse relationship
between level of current pathology and how favourably they viewed the sister
relationship. Sister relationships may suffer during AN and improve as the
pathology recedes. This would mean that the quality of sister relationships has
clinical significance and may serve as an indicator of recovery. Copyright (c)
2016 John Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 27501166
TI - Residual Carcinoma In Situ at the Ductal Stump has a Negative Survival Effect: An
Analysis of Early-stage Cholangiocarcinomas.
AB - OBJECTIVE: The aim of the study was to evaluate whether carcinoma in situ (CIS)
residue at the ductal stump affects the survival of patients undergoing resection
for extrahepatic cholangiocarcinoma. BACKGROUND: Positive ductal margin with CIS
has been treated as a tumor-free margin from a prognostic viewpoint because
several studies have reported that residual CIS foci at the ductal stump do not
affect survival after resection. METHODS: Patients who underwent resection for
extrahepatic cholangiocarcinoma were retrospectively reviewed. The surgical
margin status was histologically divided into negative (R0), positive with CIS
(R1cis), and positive with invasive cancer (R1inv). The survival and incidence of
local recurrence were compared among the groups. RESULTS: Of 684 consecutive
resected patients, 172 patients with early-stage (pTis-2N0M0) cholangiocarcinoma
(perihilar, n = 144; distal, n = 28) were analyzed. The cumulative incidence of
local recurrence in R1cis patients was higher than R0 patients (32.8% vs 4.4% at
5 years, P < 0.001) and lower than R1inv patients (50.0% at 2 years, P = 0.012).
The disease-specific survival for R1cis patients was worse than for R0 patients
(35.1% vs 78.7% at 5 years, P = 0.005) and better than for R1inv patients (40.0%
at 2 years, P = 0.002). The uni- and multivariate analyses identified the
surgical margin status as an independent prognostic factor (R1cis vs R0, relative
risk 2.39, P = 0.026; R1inv vs R0, RR 10.28, P < 0.001). CONCLUSION: R1cis
increases the incidence of local recurrence and shortens postoperative survival
in patients with early-stage cholangiocarcinoma, although this prognostic effect
was less severe compared with R1inv. R1cis should be avoided as much as possible
in surgery for early-stage cancer, although it may be allowed in advanced tumors.
PMID- 27501167
TI - Reducing Non-Anastomotic Biliary Strictures in Donation After Circulatory Death
Liver Transplantation: Cold Ischemia Time Matters!
PMID- 27501168
TI - Effectiveness of Bariatric Surgery in the Remission of Type 2 Diabetes and
Vascular Complications.
PMID- 27501169
TI - Association Between Race and Postoperative Outcomes in a Universally Insured
Population Versus Patients in the State of California.
AB - OBJECTIVE: To compare disparities in postoperative outcomes for African Americans
after surgical intervention in the universally insured military system, versus
the civilian setting in California. BACKGROUND: Health reform proponents cite the
reduction of disparities for African Americans and minorities as an expected
benefit. The impact of universal health insurance on reducing surgical
disparities for African Americans has not previously been examined. METHODS: We
used Department of Defense health insurance (Tricare) data (2006-2010) to measure
outcomes for African Americans as compared with Whites after 12 major surgical
procedures across multiple specialties. The experience of African Americans in
the Tricare system was compared with a similar cohort undergoing surgery in the
state of California using the State Inpatient Database (2007-2011). RESULTS: No
significant difference in postoperative complications [odds ratio (OR) 0.91; 95%
confidence interval (CI) 0.81, 1.03] or mortality (OR 0.98; 95% CI 0.43, 2.25)
were encountered between African Americans and Whites receiving surgery at
hospitals administered by the Department of Defense. African Americans in
California who were uninsured or on Medicaid had significantly increased odds of
mortality (OR 4.76; 95% CI 2.82, 8.05), complications (OR 1.67; 95% CI 1.34,
2.08), failure to rescue (OR 2.72; 95% CI 1.25, 5.94), and readmission (OR 1.78;
95% CI 1.45, 2.19). CONCLUSIONS: In the equal access military healthcare system,
African Americans have outcomes similar to Whites. Disparities were evident in
California, especially among those without private insurance. These facts point
toward the potential benefits of a federally administered system in which all
patients are treated uniformly.
PMID- 27501170
TI - Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and
Esophagectomy for Esophageal Cancer.
AB - OBJECTIVE: To determine whether adjuvant chemotherapy (AC) after neoadjuvant
chemoradiation and esophagectomy is associated with improved overall survival for
patients with locally advanced esophageal cancer, and to evaluate how pathologic
disease response to neoadjuvant treatment impacts this effect. BACKGROUND:
Neoadjuvant chemoradiation is currently the preferred management approach for
locoregional esophageal cancer. Although there is interest in the use of AC, the
benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is
unclear. METHODS: Retrospective cohort study of patients with esophageal cancer
treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer
Data Base (2006-2012). RESULTS: Among 3592 patients with esophageal cancer (84.7%
adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC.
AC was not associated with a significantly lower risk of death among patients
with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among
patients with residual nodal disease (ypTanyN+), AC was associated with a 30%
lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)]
and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day
postoperative landmark, findings were similar. Among patients with postoperative
length of stay <=10 days and no unplanned readmission, AC was associated with
approximately 40% lower risk of death among patients with residual nodal disease
[overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)].
CONCLUSIONS: AC after neoadjuvant chemoradiation and esophagectomy is associated
with improved survival in patients with residual nodal disease. Our findings
suggest AC may provide additional benefit for esophageal cancer patients, and
merits further investigation.
PMID- 27501171
TI - miR-221 Mediates Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting
of DKK2 Expression.
AB - BACKGROUND: Chemoresistance is a main obstacle to effective esophageal cancer
(EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a
role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based
chemotherapeutic strategies. METHODS: Four pairs of esophageal adenocarcinoma
(EAC) cell lines and corresponding 5-FU resistant variants were established. The
expression levels of miRNAs previously shown to be involved in the general
regulation of stem cell pathways were analyzed by qRT-PCR. The effects of
selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated
both in vitro and in vivo. We identified a particular miRNA and analyzed its
putative target genes in 14 pairs of human EC tumor specimens with surrounding
normal tissue by qRT-PCR as well as Wnt pathway associated genes by
immunohistochemistry in another 45 EAC tumor samples. RESULTS: MiR-221 was
overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue.
DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU
resistant cells resulted in reduced cell proliferation, increased apoptosis,
restored chemosensitivity, and led to inactivation of the Wnt/beta-catenin
pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction
resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as
well as significantly slower xenograft tumor growth in nude mice. RT profiler
analysis identified a substantial dysregulation of 4 Wnt/beta-catenin signaling
and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44,
MYC, and ABCG2. CONCLUSION: MiR-221 controls 5-FU resistance of EC partly via
modulation of Wnt/beta-catenin-EMT pathways by direct targeting of DKK2
expression. MiR-221 may serve as a prognostic marker and therapeutic target for
patients with 5-FU resistant EAC.
PMID- 27501172
TI - POST-TEXT III and IV Hepatoblastoma: Extended Hepatic Resection Avoids Liver
Transplantation in Selected Cases.
AB - OBJECTIVE: To analyze the outcome of hepatoblastoma (HB) patients presenting with
post treatment extent of disease (POST-TEXT) stages III and IV after neoadjuvant
chemotherapy. BACKGROUND: Primary liver transplantation has been advocated as
surgical treatment for children with HB involving 3 or 4 sectors at diagnosis.
However, in some cases, tumors seem resectable after chemotherapy through
aggressive use of nontransplant surgical procedures. METHODS: Data of 27 HB
patients were reviewed, undergoing extended liver resection for POST-TEXT III or
IV tumors after chemotherapy between 1992 and 2015. Median follow-up was 58
months (range 9-188). RESULTS: Median age at surgery was 18.2 months
(interquartile range 10.8-32.5). Staging of the children after chemotherapy
revealed POST-TEXT III in 21 and POST-TEXT IV in 6 cases. In 2 children, the
hepatic resection was performed under cardiopulmonary bypass because of extended
vena cava thrombosis; in 2 patients, a simultaneous sternotomy was performed for
resection of bilateral lung metastases. The 5-year overall survival rate was
80.7%. CONCLUSIONS: Aggressive surgical resection is a successful approach in
some patients with POST-TEXT III and IV HB who otherwise would be candidates for
liver transplantation. These children should undergo central review and should be
surgically managed at centers of excellence for pediatric liver surgery. Despite
challenging surgical procedures and complex clinical courses, the patients
benefit from avoidance of morbidities of organ transplant. However, preparation
of backup liver transplantation should be considered in selected cases.
PMID- 27501173
TI - Seeing the Trees For the Forest: Rectal Cancer Intratumoral Heterogeneity.
PMID- 27501174
TI - Primary Pancreatic Secretinoma: Further Evidence Supporting Secretin as a
Diarrheogenic Hormone.
AB - OBJECTIVES: To document the existence of primary pancreatic secretinoma in
patients with watery diarrhea syndrome (WDS) and achlorhydria and establish
secretin as a diarrheogenic hormone. BACKGROUND: Vasoactive intestinal peptide
(VIP) has been widely accepted as the main mediator of WDS. However, in 1968,
Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors,
WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they
noticed distended duodenum filled with fluid and a dilated gallbladder containing
dilute bile with high bicarbonate concentration. After excision of the tumor, WDS
ceased and gastric acid secretion returned. The second, a 47-year-old, patient's
metastatic tumor extract given intravenously in dogs, produced significantly
increased pancreatic and biliary fluid rich in bicarbonate. They suggested a
secretin-like hormone of islet cell origin explains WDS and achlorhydria. These
observations, however, predated radioimmunoassay, immunohistochemical staining,
and other molecular studies. METHODS: The first patient's tumor tissue was
investigated for secretin and VIP. Using both immunohistochemistry and laser
microdissection and pressure catapulting technique for RNA isolation and
subsequent reverse transcription polymerase chain reaction, the expression levels
of secretin, and VIP were measured. RESULTS: Immunoreactive secretin and its mRNA
were predominantly found in the tumor tissue whereas VIP and its mRNA were
scarce. CONCLUSIONS: The findings strongly support that the WDS and achlorhydria
in this patient may have been caused by secretin as originally proposed in 1968
and that secretin may act as a diarrheogenic hormone.
PMID- 27501175
TI - Measuring the Value of a Clinical Practice Guideline for Children With Perforated
Appendicitis.
AB - OBJECTIVE: To determine the incremental cost-effectiveness of a clinical practice
guideline (CPG) compared with "usual care" for treatment of perforated
appendicitis in children. Secondary objective was to compare cost analyses using
hospital accounting system data versus data in the Pediatric Health Information
System (PHIS). BACKGROUND: Value-based surgical care (outcomes relative to costs)
is frequently touted, but outcomes and costs are rarely measured together.
METHODS: During an 18-month period, 122 children with perforated appendicitis at
a tertiary referral children's hospital were treated using an evidence-based CPG.
Clinical outcomes and costs for the CPG cohort were compared with patients in the
30-month period before CPG implementation (n = 191 children). RESULTS: With CPG
directed care, intra-abdominal abscess rate decreased from 0.24 to 0.10 (adjusted
risk ratio 0.44, 95% confidence interval [CI] 0.26-0.75). The rate of any adverse
event decreased from 0.30 to 0.23 (adjusted risk ratio 0.82, 95% CI 0.58-1.17).
Mean total hospital costs per patient (hospital accounting system) decreased from
$16,466 to $10,528 (adjusted absolute difference-$5451, 95% CI -$7755 to -$3147),
leading to estimated adjusted total savings of $665,022 during the study period.
Costs obtained from the PHIS database also showed reduction with CPG-directed
care (-$6669, 95% CI -$8949 to -$4389 per patient). In Bayesian cost
effectiveness analyses, likelihood that CPG was the dominant strategy was 91%.
CONCLUSIONS: An evidence-based CPG increased the value of surgical care for
children with perforated appendicitis by improving outcomes and lowering costs.
Hospital cost accounting data and pre-existing cost data within the PHIS database
provided similar results.
PMID- 27501177
TI - Reply to Letter: "Esophageal Cancer: Long-term Survival and Day of Surgery".
PMID- 27501176
TI - Trajectory of Functional Recovery After Postoperative Delirium in Elective
Surgery.
AB - OBJECTIVE: To describe functional recovery after elective surgery and to
determine whether improvements differ among individuals who develop delirium.
BACKGROUND: No large studies of older adults have investigated whether delirium
influences the trajectory of functional recovery after elective surgery. The
prospective observational study assessed this association among 566 individuals
aged 70 years and older. METHODS: Patients undergoing major elective surgery were
assessed daily while in hospital for presence and severity of delirium using the
Confusion Assessment Method, and their functional recovery was followed for 18
months thereafter. The Activities of Daily Living and Instrumental Activities of
Daily Living Scales and the Physical Component Summary of the Short Form-12 were
obtained before surgery and at 1, 2, 6, 12, and 18 months. A composite index
(standard deviation 10, minimally clinically significant difference 2) derived
from these scales was then analyzed using mixed-effects regression. RESULTS: Mean
age was 77 years; 58% of participants were women and 24% developed postoperative
delirium. Participants with delirium demonstrated lesser functional recovery than
their counterparts without delirium; at 1 month, the covariate-adjusted mean
difference on the physical function composite was -1.5 (95% confidence interval
3.3, -0.2). From 2 to 18 months, the corresponding difference was -1.8 (95%
confidence interval -3.2, -0.3), an effect comparable with the minimally
clinically significant difference. CONCLUSIONS: Delirium was associated with
persistent and clinically meaningful impairment of functional recovery, to 18
months. Use of multifactorial preventive interventions for patients at high risk
for delirium and tailored transitional care planning may help to maximize the
functional benefits of elective surgery.
PMID- 27501178
TI - Commentary on Hand Laterality and Acquired Ambidexterity in Surgical Training.
PMID- 27501179
TI - A System to Create Stable Nanoparticle Aerosols from Nanopowders.
AB - Nanoparticle aerosols released from nanopowders in workplaces are associated with
human exposure and health risks. We developed a novel system, requiring minimal
amounts of test materials (min. 200 mg), for studying powder aerosolization
behavior and aerosol properties. The aerosolization procedure follows the concept
of the fluidized-bed process, but occurs in the modified volume of a V-shaped
aerosol generator. The airborne particle number concentration is adjustable by
controlling the air flow rate. The system supplied stable aerosol generation
rates and particle size distributions over long periods (0.5-2 hr and possibly
longer), which are important, for example, to study aerosol behavior, but also
for toxicological studies. Strict adherence to the operating procedures during
the aerosolization experiments ensures the generation of reproducible test
results. The critical steps in the standard protocol are the preparation of the
material and setup, and the aerosolization operations themselves. The system can
be used for experiments requiring stable aerosol concentrations and may also be
an alternative method for testing dustiness. The controlled aerosolization made
possible with this setup occurs using energy inputs (may be characterized by
aerosolization air velocity) that are within the ranges commonly found in
occupational environments where nanomaterial powders are handled. This setup and
its operating protocol are thus helpful for human exposure and risk assessment.
PMID- 27501180
TI - Disrupted-in-schizophrenia-1 as a broader link of glutamatergic transmission to
schizophrenia impacts cerebral neurochemistry via the production of the
'gliotransmitter' d-serine, a NMDA receptor coagonist.
AB - This Editorial highlights a study by Xia and coworkers in the current issue of
the Journal of Neurochemistry, in which the authors reveal a possible mechanistic
link between DISC1 (disrupted-in-schizophrenia-1), a genetic risk factor for
schizophrenia, and N-methyl-d-aspartate receptor (NMDAR) that is also linked with
schizophrenia. The authors show that perturbed communication between DISC1 and
NMDARs represents a hidden perpetrator for abnormal dendritic and synaptic
maturation. Read the highlighted article 'DISC1, astrocytes and neuronal
maturation: a possible mechanistic link with implications for mental disorders'
on page 518.
PMID- 27501181
TI - Corrigendum.
PMID- 27501182
TI - Type 2 Deiodinase Disruption in Astrocytes Results in Anxiety-Depressive-Like
Behavior in Male Mice.
AB - Millions of levothyroxine-treated hypothyroid patients complain of impaired
cognition despite normal TSH serum levels. This could reflect abnormalities in
the type 2 deiodinase (D2)-mediated T4-to-T3 conversion, given their much greater
dependence on the D2 pathway for T3 production. T3 normally reaches the brain
directly from the circulation or is produced locally by D2 in astrocytes. Here we
report that mice with astrocyte-specific Dio2 inactivation (Astro-D2KO) have
normal serum T3 but exhibit anxiety-depression-like behavior as found in open
field and elevated plus maze studies and when tested for depression using the
tail-suspension and the forced-swimming tests. Remarkably, 4 weeks of daily
treadmill exercise sessions eliminated this phenotype. Microarray gene expression
profiling of the Astro-D2KO hippocampi identified an enrichment of three gene
sets related to inflammation and impoverishment of three gene sets related to
mitochondrial function and response to oxidative stress. Despite normal
neurogenesis, the Astro-D2KO hippocampi exhibited decreased expression of four of
six known to be positively regulated genes by T3, ie, Mbp (~43%), Mag (~34%), Hr
(~49%), and Aldh1a1 (~61%) and increased expression of 3 of 12 genes negatively
regulated by T3, ie, Dgkg (~17%), Syce2 (~26%), and Col6a1 (~3-fold) by
quantitative real-time PCR. Notably, in Astro-D2KO animals, there was also a
reduction in mRNA levels of genes known to be affected in classical animal models
of depression, ie, Bdnf (~18%), Ntf3 (~43%), Nmdar (~26%), and GR (~20%), which
were also normalized by daily exercise sessions. These findings suggest that
defects in Dio2 expression in the brain could result in mood and behavioral
disorders.
PMID- 27501183
TI - beta-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose
Tolerance After Vertical Sleeve Gastrectomy.
AB - Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes
remission; however, the mechanisms responsible for this remain incompletely
defined. Glucagon-like peptide-1 (GLP-1) is a gut hormone that contributes to the
maintenance of glucose homeostasis and is elevated after VSG. VSG-induced
increases in postprandial GLP-1 secretion have been proposed to contribute to the
glucoregulatory benefits of VSG; however, previous work has been equivocal. In
order to test the contribution of enhanced beta-cell GLP-1 receptor (GLP-1R)
signaling we used a beta-cell-specific tamoxifen-inducible GLP-1R knockout mouse
model. Male beta-cell-specific Glp-1r(beta-cell+/+) wild type (WT) and Glp
1r(beta-cell-/-) knockout (KO) littermates were placed on a high-fat diet for 6
weeks and then switched to high-fat diet supplemented with tamoxifen for the rest
of the study. Mice underwent sham or VSG surgery after 2 weeks of tamoxifen diet
and were fed ad libitum postoperatively. Mice underwent oral glucose tolerance
testing at 3 weeks and were euthanized at 6 weeks after surgery. VSG reduced body
weight and food intake independent of genotype. However, glucose tolerance was
only improved in VSG WT compared with sham WT, whereas VSG KO had impaired
glucose tolerance relative to VSG WT. Augmentation of glucose-stimulated insulin
secretion during the oral glucose tolerance test was blunted in VSG KO compared
with VSG WT. Therefore, our data suggest that enhanced beta-cell GLP-1R signaling
contributes to improved glucose regulation after VSG by promoting increased
glucose-stimulated insulin secretion.
PMID- 27501185
TI - Vasoactive Intestinal Peptide Excites GnRH Neurons in Male and Female Mice.
AB - A variety of external and internal factors modulate the activity of GnRH neurons
to control fertility in mammals. A direct, vasoactive intestinal peptide (VIP)
mediated input to GnRH neurons originating from the suprachiasmatic nucleus is
thought to relay circadian information within this network. In the present study,
we examined the effects of VIP on GnRH neuron activity in male and female mice at
different stages of the estrous cycle. We carried out cell-attached recordings in
slices from GnRH-green fluorescent protein mice and calcium imaging in slices
from a mouse line expressing the genetically encoded calcium indicator GCaMP3
selectively in GnRH neurons. We show that 50%-80% of GnRH neurons increase their
firing rate in response to bath-applied VIP (1nM-1000nM) in both male and female
mice and that this is accompanied by a robust increase in intracellular calcium
concentrations. This effect is mediated directly at the GnRH neuron likely
through activation of high-affinity VIP receptors. Because suprachiasmatic
nucleus-derived timing cues trigger the preovulatory surge only on the afternoon
of proestrus in female mice, we examined the effects of VIP during the estrous
cycle at different times of day. VIP responsiveness in GnRH neurons did not vary
significantly in diestrous and proestrous mice before or around the time of the
expected preovulatory surge. These results indicate that the majority of GnRH
neurons in male and female mice express functional VIP receptors and that the
effects of VIP on GnRH neurons do not alter across the estrous cycle.
PMID- 27501184
TI - Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic
Vascularity, and Islet Size in Growth-Restricted Fetal Sheep.
AB - Placental insufficiency is associated with reduced supply of amino acids to the
fetus and leads to intrauterine growth restriction (IUGR). IUGR fetuses are
characterized by lower glucose-stimulated insulin secretion, smaller pancreatic
islets with less beta-cells, and impaired pancreatic vascularity. To test whether
supplemental amino acids infused into the IUGR fetus could improve these
complications of IUGR we used acute (hours) and chronic (11 d) direct fetal amino
acid infusions into a sheep model of placental insufficiency and IUGR near the
end of gestation. IUGR fetuses had attenuated acute amino acid-stimulated insulin
secretion compared with control fetuses. These results were confirmed in isolated
IUGR pancreatic islets. After the chronic fetal amino acid infusion, fetal
glucose-stimulated insulin secretion and islet size were restored to control
values. These changes were associated with normalization of fetal pancreatic
vascularity and higher fetal pancreatic vascular endothelial growth factor A
protein concentrations. These results demonstrate that decreased fetal amino acid
supply contributes to the pathogenesis of pancreatic islet defects in IUGR.
Moreover, the results show that pancreatic islets in IUGR fetuses retain their
ability to respond to increased amino acids near the end of gestation after
chronic fetal growth restriction.
PMID- 27501186
TI - The Circadian Timing System and Environmental Circadian Disruption: From
Follicles to Fertility.
AB - The internal or circadian timing system is deeply integrated in female
reproductive physiology. Considerable details of rheostatic timing function in
the neuroendocrine control of pituitary hormone secretion, adenohypophyseal
hormone gene expression and secretion, gonadal steroid hormone biosynthesis and
secretion, ovulation, implantation, and parturition have been reported. The
molecular clock, an autonomous feedback loop oscillator of interacting
transcriptional regulators, dictates the timing and amplitude of gene expression
in each tissue of the female hypothalamic-pituitary-gonadal (HPG) axis. Although
multiple targets of the molecular clock have been identified, many associated
with critical physiological functions in the HPG axis, the full extent of clock
driven gene expression and physiology in this critical system remains unknown.
Environmental circadian disruption (ECD), the disturbance of temporal
relationships within and between internal clocks (brain and periphery), and
external timing cues (eg, light, nutrients, social cues) due to rotating/night
shift work or transmeridian travel have been linked to reproductive dysfunction
and subfertility. Moreover, ECD resulting from exposure to endocrine disrupting
chemicals, environmental toxins, and/or irregular hormone levels during sexual
development can also reduce fertility. Thus, perturbations that disturb clock
function at the molecular, cellular or systemic level correlate with significant
declines in female reproductive function. Here we briefly review the evidence for
molecular clock function in each tissue of the female HPG axis (GnRH neuron,
pituitary, uterus, oviduct, and ovary), describe the human epidemiological and
animal data supporting the negative effects of ECD on fertility, and explore the
potential for novel chronotherapeutics in women's health and fertility.
PMID- 27501187
TI - Standard PK/PD concepts can be applied to determine a dosage regimen for a
macrolide: the case of tulathromycin in the calf.
AB - The pharmacokinetic (PK) profile of tulathromycin, administered to calves
subcutaneously at the dosage of 2.5 mg/kg, was established in serum, inflamed
(exudate), and noninflamed (transudate) fluids in a tissue cage model. The PK
profile of tulathromycin was also established in pneumonic calves. For Mannheimia
haemolytica and Pasteurella multocida, tulathromycin minimum inhibitory
concentrations (MIC) were approximately 50 times lower in calf serum than in
Mueller-Hinton broth. The breakpoint value of the PK/pharmacodynamic (PD) index
(AUC(0-24 h) /MIC) to achieve a bactericidal effect was estimated from in vitro
time-kill studies to be approximately 24 h for M. haemolytica and P. multocida. A
population model was developed from healthy and pneumonic calves and, using Monte
Carlo simulations, PK/PD cutoffs required for the development of antimicrobial
susceptibility testing (AST) were determined. The population distributions of
tulathromycin doses were established by Monte Carlo computation (MCC). The
computation predicted a target attainment rate (TAR) for a tulathromycin dosage
of 2.5 mg/kg of 66% for M. haemolytica and 87% for P. multocida. The findings
indicate that free tulathromycin concentrations in serum suffice to explain the
efficacy of single-dose tulathromycin in clinical use, and that a dosage regimen
can be computed for tulathromycin using classical PK/PD concepts.
PMID- 27501188
TI - Improved Swiss-rolling Technique for Intestinal Tissue Preparation for
Immunohistochemical and Immunofluorescent Analyses.
AB - Understanding the role of factors that regulate intestinal epithelial homeostasis
and response to injury and regeneration is important. The current literature
describes several different methodological approaches to obtain images of
intestinal tissues for data validation. In this paper, we delineate a common
protocol relating to the derivation and processing of mouse intestinal tissues.
Proper fixation of intestinal tissues and Swiss-roll techniques that enhance
intestinal epithelial morphology are discussed. Postresection processing and
reorientation of embedded intestinal tissues are critical in obtaining paraffin
embedded blocks that display intact intestinal structural features after
sectioning. The Swiss-rolling technique helps in histological assessment of the
complete intestinal or colonic sections examined. An ability to differentiate
intestinal structural features can be vital in quantitative measurements of
intestinal inflammation and tumorigenesis along the entire length. Finally,
paraffin-embedded sections are ideal for robust processing using both
immunohistochemical and immunofluorescent detection methods. Nonfluorescent
immunohistochemical sections provide a vibrant image of the tissue detailing
different cellular structural features but do not provide flexibility for
intracellular co-localization experiments. Multiple fluorescent channels can be
appropriately utilized with immunofluorescent detection for co-localization
experiments, lending support to mechanistic studies.
PMID- 27501189
TI - Validity and reliability of the Family Empowerment Scale for caregivers of adults
with mental health issues.
AB - : WHAT IS KNOWN ON THE SUBJECT?: Empowerment of family caregivers of adults with
mental health issues has received increasing attention among mental health nurses
in Japan and has been recognized as a new goal of family interventions. The
Family Empowerment Scale (FES) was originally developed to measure the
empowerment status of parents of children with emotional disorders. However, it
was later applied to broader health issues. WHAT THIS PAPER ADDS TO EXISTING
KNOWLEDGE?: We developed a Japanese version of the FES for family caregivers of
adults with mental health issues (FES-AMJ) and examined the validity and
reliability among parents. Results showed that the FES-AMJ had acceptable
concurrent validity and reliability; however, insufficient construct validity was
found, especially for the subscale regarding the service system. WHAT ARE THE
IMPLICATIONS FOR PRACTICE?: Further studies need to modify the scale.
Clarification of ideal family empowerment status in the service system through
discussion with mental health nurses and family caregivers may be important.
ABSTRACT: Introduction The Family Empowerment Scale (FES) was originally
developed for parents of children with emotional disorders. In Japan, family
empowerment is gaining increasing attention and may be one goal of nursing
interventions. Aim To develop a Japanese version of the FES for family caregivers
of adults with mental health issues and to study the validity and reliability of
this scale among parents. Method We translated the FES into Japanese and
administered this self-report questionnaire to 275 parents. Results The
multitrait scaling analysis revealed acceptable convergent validity and
insufficient discriminant validity among all subscales. In particular, all items
of the Service system subscale had insufficient discriminant and/or convergent
validity. Each subscale significantly correlated with the indicator of
empowerment. The intraclass correlation coefficients of each subscale were .855
.917. Cronbach's alpha of each factor ranged from .867 to .895. Discussion The
Service system subscale may not linearly reflect family empowerment, and instead
may depend on unclear roles of family caregivers of adults, disorder severity or
insufficient services. Implications for practice Further studies need to modify
the scale. Clarification of ideal family empowerment status in the service system
through discussion with mental health nurses and family caregivers may be
important.
PMID- 27501190
TI - Whole genome sequence resource of Indian Zaprionus indianus.
AB - This article documents the whole genome sequence information of the Indian
Zaprionus indianus, a member of the fruit fly family Drosophilidae. The sequences
were generated on an Illumina platform and reads and whole genome sequence
submitted to NCBI to the SRA and BioProject databases, respectively. This is the
first Indian Z. indianus whole genome (draft) submitted to the sequence
repository with SRA reads. The details of methodology, assembly statistics and
functional annotation are presented in this work.
PMID- 27501191
TI - Placental Growth Measures in Relation to Birth Weight in a Latin American
Population.
AB - Introduction The placenta, translates how the fetus experiences the maternal
environment and is a principal influence on birth weight (BW). Objective To
explore the relationship between placental growth measures (PGMs) and BW in a
public maternity hospital. Methods Observational retrospective study of 870
singleton live born infants at Hospital Maternidad Sarda, Universidad de Buenos
Aires, Argentina, between January 2011 and August 2012 with complete data of
PGMs. Details of history, clinical and obstetrical maternal data, labor and
delivery and neonatal outcome data, including placental measures derived from the
records, were evaluated. The following manual measurements of the placenta
according to standard methods were performed: placental weight (PW, g), larger
and smaller diameters (cm), eccentricity, width (cm), shape, area (cm(2)), BW/PW
ratio (BPR) and PW/BW ratio (PBR), and efficiency. Associations between BW and
PGMs were examined using multiple linear regression. Results Birth weight was
correlated with placental weight (R(2) = 0.49, p < 0.001), whereas gestational
age was moderately correlated with placental weight (R(2) = 0.64, p < 0.001). By
gestational age, there was a positive trend for PW and BPR, but an inverse
relationship with PBR (p < 0.001). Placental weight alone accounted for 49% of
birth weight variability (p < 0,001), whereas all PGMs accounted for 52% (p <
0,001). Combined, PGMs, maternal characteristics (parity, pre-eclampsia, tobacco
use), gestational age and gender explained 77.8% of BW variations (p < 0,001).
Among preterm births, 59% of BW variances were accounted for by PGMs, compared
with 44% at term. All placental measures except BPR were consistently higher in
females than in males, which was also not significant. Indices of placental
efficiency showed weakly clinical relevance. Conclusions Reliable measures of
placental growth estimate 53.6% of BW variances and project this outcome to a
greater degree in preterm births than at term. These findings would contribute to
the understanding of the maternal-placental programming of chronic diseases.
PMID- 27501192
TI - Organic Lasers: Recent Developments on Materials, Device Geometries, and
Fabrication Techniques.
AB - Organic dyes have been used as gain medium for lasers since the 1960s, long
before the advent of today's organic electronic devices. Organic gain materials
are highly attractive for lasing due to their chemical tunability and large
stimulated emission cross section. While the traditional dye laser has been
largely replaced by solid-state lasers, a number of new and miniaturized organic
lasers have emerged that hold great potential for lab-on-chip applications,
biointegration, low-cost sensing and related areas, which benefit from the unique
properties of organic gain materials. On the fundamental level, these include
high exciton binding energy, low refractive index (compared to inorganic
semiconductors), and ease of spectral and chemical tuning. On a technological
level, mechanical flexibility and compatibility with simple processing techniques
such as printing, roll-to-roll, self-assembly, and soft-lithography are most
relevant. Here, the authors provide a comprehensive review of the developments in
the field over the past decade, discussing recent advances in organic gain
materials, which are today often based on solid-state organic semiconductors, as
well as optical feedback structures, and device fabrication. Recent efforts
toward continuous wave operation and electrical pumping of solid-state organic
lasers are reviewed, and new device concepts and emerging applications are
summarized.
PMID- 27501193
TI - Visualizing Motion Patterns in Acupuncture Manipulation.
AB - Acupuncture manipulation varies widely among practitioners in clinical settings,
and it is difficult to teach novice students how to perform acupuncture
manipulation techniques skillfully. The Acupuncture Manipulation Education System
(AMES) is an open source software system designed to enhance acupuncture
manipulation skills using visual feedback. Using a phantom acupoint and motion
sensor, our method for acupuncture manipulation training provides visual feedback
regarding the actual movement of the student's acupuncture manipulation in
addition to the optimal or intended movement, regardless of whether the
manipulation skill is lifting, thrusting, or rotating. Our results show that
students could enhance their manipulation skills by training using this method.
This video shows the process of manufacturing phantom acupoints and discusses
several issues that may require the attention of individuals interested in
creating phantom acupoints or operating this system.
PMID- 27501194
TI - Capturing the Active Ingredients of Multicomponent Participatory Organizational
Stress Interventions Using an Adapted Study Design.
AB - Adapted study designs use process evaluation to incorporate a measure of
intervention exposure and create an artificial control and intervention groups.
Taking into account exposure levels to interventions combines process and outcome
evaluation and strengthens the design of the study when exposure levels cannot be
controlled. This study includes longitudinal data (two assessments) with added
process measures at time 2 gathered from three complex participatory intervention
projects in Canada in a hospital and a university. Structural equation modelling
was used to explore the specific working mechanisms of particular interventions
on stress outcomes. Results showed that higher exposure to interventions aiming
to modify tasks and working conditions reduced demands and improved social
support, but not job control, which in turn, reduced psychological distress.
Exposure to interventions aiming to improve relationships was not related to
psychosocial risks. Most studies cannot explain how interventions produce their
effects on outcomes, especially when there are multiple concurrent interventions
delivered in several contexts. This study advances knowledge on process
evaluation by using an adapted study design to capture the active ingredients of
multicomponent interventions and suggesting some mechanisms by which the
interventions produce their effects on stress outcomes. It provides an
illustration of how to conduct process evaluation and relate exposure levels to
observed outcomes. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501195
TI - A protein complex supports the production of Spo0A-P and plays additional roles
for biofilms and the K-state in Bacillus subtilis.
AB - Bacillus subtilis can enter three developmental pathways to form spores, biofilms
or K-state cells. The K-state confers competence for transformation and
antibiotic tolerance. Transition into each of these states requires a stable
protein complex formed by YlbF, YmcA and YaaT. We have reported that this complex
acts in sporulation by accelerating the phosphorylation of the response regulator
Spo0A. Phosphorelay acceleration was also predicted to explain their involvement
in biofilm formation and the K-state. This view has been challenged in the case
of biofilms, by the suggestion that the three proteins act in association with
the mRNA degradation protein RNaseY (Rny) to destabilize the sinR transcript.
Here, we reaffirm the roles of the three proteins in supporting the
phosphorylation of Spo0A for all three developmental pathways and show that in
their absence sinR mRNA is not stabilized. We demonstrate that the three proteins
also play unknown Spo0A-P-independent roles in the expression of biofilm matrix
and in the production of ComK, the master transcription factor for competence.
Finally, we show that domesticated strains of B. subtilis carry a mutation in
sigH, which influences the expression kinetics of the early spore gene spoIIG,
thereby increasing the penetrance of the ylbF, ymcA and yaaT sporulation
phenotypes.
PMID- 27501196
TI - Enhanced viral activity and dark CO2 fixation rates under oxygen depletion: the
case study of the marine Lake Rogoznica.
AB - Global change is determining the expansion of marine oxygen-depleted zones, which
are hot spots of microbial-driven biogeochemical processes. However, information
on the functioning of the microbial assemblages and the role of viruses in such
low-oxygen systems remains largely unknown. Here, we used the marine Rogoznica
Lake as a natural model to investigate the possible consequences of oxygen
depletion on virus-prokaryote interactions and prokaryotic metabolism in pelagic
and benthic ecosystems. We found higher bacterial and archaeal abundances in
oxygen-depleted than in oxic conditions, associated with higher heterotrophic
carbon production, enzymatic activities and dark inorganic carbon fixation (DCF)
rates. The oxygen-depleted systems were also characterized by higher viral
abundance, production and virus-induced prokaryotic mortality. The highest DCF
relative contribution to the whole total C production (> 30%) was found in oxygen
depleted systems, at the highest virus-induced prokaryotic mortality values (>
90%). Our results suggest that the higher rates of viral lysis in oxygen-depleted
conditions can significantly enhance DCF by accelerating heterotrophic processes,
organic matter cycling, and hence the supply of inorganic reduced compounds
fuelling chemosynthesis. These findings suggest that the expansion of low-oxygen
zones can trigger higher viral impacts on prokaryotic heterotrophic and
chemoautotrophic metabolism, with cascading effects, neglected so far, on
biogeochemical processes.
PMID- 27501197
TI - Family-centered care in children with epilepsy: Evaluating the Measure of
Processes of Care (MPOC-20).
AB - OBJECTIVE: The objective was to test whether the five-domain structure of the
Measure of Processes of Care (MPOC-20) was observed in a sample of children with
epilepsy and, if not, to propose adaptations to improve its utility in this
population. METHODS: Data came from the Health-Related Quality of Life in
Children with Epilepsy Study (HERQULES)-a multicenter prospective cohort study (n
= 374) following children 4-12 years of age for 2 years after diagnosis.
Confirmatory factor analysis (CFA) tested the applicability of the five
domains/factors in a sample of children with epilepsy approximately 6 months
following diagnosis (n = 311). Goodness-of-fit statistics were used to examine
sources of ill model fit, and modification indices guided the model modification
process where there was strong theoretical rationale for changes. RESULTS: The
five-factor model described by the originators of the MPOC-20 was found to be
inadmissible in children with epilepsy, with four of the five factors
demonstrating high correlations (r > 0.85). Upon merging the intercorrelated
factors, a two-factor solution with a mediocre fit emerged (Root Mean Square
Error of Approximation (RMSEA) = 0.080, Comparative Fit Index (CFI) = 0.902,
Standardized Root Mean Square Residual (SRMR) = 0.060). Modification indices
identified four items as the source of poor model fit. Removing these four items
and reperforming the CFA resulted in an adequate model fit and a revised 16-item
MPOC (RMSEA = 0.057, CFI = 0.958, SRMR = 0.036). The two factors are "Family/Care
Provider Interaction" and "Providing Information." SIGNIFICANCE: Results suggest
that the MPOC-16 better reflects family-centered care (FCC) in children with
epilepsy than the original MPOC-20. The benefit of having fewer factors is that
scoring is simpler and the interpretation of the results is easier. This was the
first investigation of the factor structure of the MPOC-20 on a sample entirely
composed of children with epilepsy. These results add to evidence that the factor
structure (and how family-centered care is delivered and perceived) differs
across treatment environments and treatment populations.
PMID- 27501198
TI - Modified partial maxillary swing approach for myxofibrosarcoma in pterygopalatine
fossa.
AB - BACKGROUND: Extirpation of tumors arising in the pterygopalatine fossa is
challenging because of its anatomic complexity. METHODS AND RESULTS: A 67-year
old man was referred to our department with a diagnosis of a tumor in his left
pterygoid fossa. An incisional biopsy through the canine fossa was diagnosed as
myxofibrosarcoma. The upper part of the maxilla was swung laterally to remove the
tumor while the hard plate was preserved. The defect was reconstructed using
rectus abdominis musculocutaneous free and ipsilateral temporal. The
postoperative course was uneventful, without facial palsy or mastication
disorders. CONCLUSION: Our experience with this case suggests that the modified
partial maxillary swing approach with preservation of the hard palate and orbital
floor in combination with infratemporal and cervical approaches is useful for
lesions in the pterygoid process without causing severe complications. (c) 2016
Wiley Periodicals, Inc. Head Neck 38: E2519-E2522, 2016.
PMID- 27501200
TI - Environment-dependent variation in selection on life history across small spatial
scales.
AB - Variation in life-history traits is ubiquitous, even though genetic variation is
thought to be depleted by selection. One potential mechanism for the maintenance
of trait variation is spatially variable selection. We explored spatial variation
in selection in the field for a colonial marine invertebrate that shows
phenotypic differences across a depth gradient of only 3 m. Our analysis included
life-history traits relating to module size, colony growth, and phenology.
Directional selection on colony growth varied in strength across depths, while
module size was under directional selection at one depth but not the other.
Differences in selection may explain some of the observed phenotypic
differentiation among depths for one trait but not another: instead, selection
should actually erode the differences observed for this trait. Our results
suggest selection is not acting alone to maintain trait variation within and
across environments in this system.
PMID- 27501201
TI - Free anterolateral thigh flap and masseter nerve transfer for reconstruction of
extensive periauricular defects: Surgical technique and clinical outcomes.
AB - BACKGROUND: Radical tumor ablation in the periauricular area often results in
extensive soft tissue defects, including facial nerve sacrifice, bone and/or dura
defects. Reconstruction of these defects should aim at restoring facial
reanimation, wound closure, and facial and neck contours. We present our
experience using free anterolateral thigh flap (ALT) in combination with masseter
nerve to facial nerve transfer in managing complex defects in the periauricular
area. METHODS: Between 2011 and 2015 six patients underwent a combined procedure
of ALT flap reconstruction and masseter nerve transfer, to reconstruct extensive,
post tumor resection, periauricular defects. The ALT flap was customized
according to the defect. For smile restoration, the masseter nerve was
transferred to the buccal branch of the facial nerve. If the facial nerve stump
was preserved, interposition of nerve grafts to the zygomatic and frontal
branches was performed to provide separate eye closure. The outcomes were
analyzed by assessing wound closure, contour deformity, symmetry of the face, and
facial nerve function. RESULTS: There were no partial or total flap losses.
Stable wound closure and adequate volume replacement in the neck was achieved in
all cases, as well as good facial tonus and symmetry. The mean follow-up time of
clinical outcomes was 16.8 months. Smile restoration was graded as good or
excellent in four cases, moderate in one and fair in one. CONCLUSION: Extensive
periauricular defects following oncologic resection could be adequately
reconstructed in a combined procedure of free ALT flap and masseter nerve
transfer to the facial nerve for smile restoration.
PMID- 27501202
TI - Enhanced detection performance in electrosense through capacitive sensing.
AB - Weakly electric fish emit an AC electric field into the water and use thousands
of sensors on the skin to detect field perturbations due to surrounding objects.
The fish's active electrosensory system allows them to navigate and hunt, using
separate neural pathways and receptors for resistive and capacitive
perturbations. We have previously developed a sensing method inspired by the
weakly electric fish to detect resistive perturbations and now report on an
extension of this system to detect capacitive perturbations as well. In our
method, an external object is probed by an AC field over multiple frequencies. We
present a quantitative framework that relates the response of a capacitive object
at multiple frequencies to the object's composition and internal structure, and
we validate this framework with an electrosense robot that implements our
capacitive sensing method. We define a metric for comparing the electrosensory
range of different underwater electrosense systems. For detecting non-conductive
objects, we show that capacitive sensing performs better than resistive sensing
by almost an order of magnitude using this measure, while for conductive objects
there is a four-fold increase in performance. Capacitive sensing could therefore
provide electric fish with extended sensing range for capacitive objects such as
prey, and gives artificial electrolocation systems enhanced range for targets
that are capacitive.
PMID- 27501204
TI - Benzodiazepine dependence in subjects with alcohol use disorders: what
prevalence?
AB - OBJECTIVE: To our knowledge, no studies have been conducted in France on
benzodiazepine (BZD) dependence among outpatients with alcohol use disorders
(AUD). Some international studies have been conducted on the consumption of BZD
in this specific population, but the comparisons among them are difficult. We
aimed to assess the current prevalence of probable benzodiazepine and BZD-like
hypnotics (Z-drugs) dependence among outpatients seeking treatment for AUD.
METHODS: Participants were patients seeking treatment for AUD for the first time
or repeating treatment after more than twelve months. Recruitment took place in
seven addiction centres between January and December 2013 in the Nantes region
(France). BZD/Z-drug dependence was assessed according to the DSM-IV diagnostic
criteria for dependence. This information was gathered through a self-report
questionnaire. RESULTS: Among the 1005 patients included in this study, 413 were
BZD/Z-drug users (41.1%). Among the 413 patients, 217 were probably dependent on
at least one substance, which represents 21.6% of the total population and 52.5%
of BZD/Z-drug users. CONCLUSION: BZD/Z-drug dependence represents a public health
concern. Prescribers should take the risks into account and keep treatment
courses to a minimum.
PMID- 27501203
TI - Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for
Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.
AB - The lack of a reliable immunosuppressive regimen that effectively suppresses both
renal and islet allograft rejection without islet toxicity hampers a wider
clinical application of simultaneous islet-kidney transplantation (SIK). Seven
MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients
received rabbit antithymocyte globulin (ATG) induction followed by daily
tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with
anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory
therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor
alpha mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to
achieve long-term islet allograft survival (19 and 26 days) due to poor islet
engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen
provided long-term islet and kidney allograft survival (90, 94, >120, >120, and
>120 days), with only one recipient developing evidence of allograft rejection.
The aCD40/Rapa regimen was also tested in four kidney-alone transplant
recipients. All four recipients achieved long-term renal allograft survival (100%
at day 120), which was superior to renal allograft survival (62.9% at day 120)
with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and
steroids). The combination of anti-CD40 mAb and rapamycin is an effective and
nontoxic immunosuppressive regimen that uses only clinically available agents for
kidney and islet recipients.
PMID- 27501205
TI - Reconsidering Empathy in Nursing Care.
PMID- 27501206
TI - Men in Nursing: Intention, Intentionality, Caring, and Healing: Emphasis on the
Results of a Grounded Theory Study.
AB - The purpose of this article is to amplify the results section of a grounded
theory study on how men in nursing view and experience intention, intentionality,
caring, and healing. This is the second grounded theory study addressing
intentionality in healing. The first study included a female population. The
theory that was generated-Intentionality: The Matrix of Healing (IMH)-is examined
with these new data. The results are compared with issues generally faced by men
in nursing and how they described their beliefs and experiences with
intentionality and healing. The theory (IMH) is supported; the importance of
action in this cohort was an additional emphasis. This article provides an
expanded view of men in nursing and their experiences as nurses and with
intentionality, caring, and healing and has implications for the development of
holistic nursing theory as well.
PMID- 27501207
TI - Effect of Acupressure on Nausea-Vomiting in Patients With Acute Myeloblastic
Leukemia.
AB - The aim of this study was to assess the effect of acupressure, applied at P6
(Neiguan) acupuncture point, on chemotherapy-induced nausea and vomiting in
patients with acute myeloblastic leukemia. This was a randomized controlled trial
conducted on patients with myeloblastic leukemia. A total of 90 patients, who
received the same chemotherapy regimen and antiemetic therapy, were included in
the study as 30 patients in the control group, 30 patients in the band group, and
30 patients in the pressure group. Although acupressure was applied by placing
wristbands at P6 acupuncture point of both wrists in patients of the band group
for totally 4 days, acupressure was applied with the use of finger pressure in
patients of the pressure group for totally 4 days. No intervention was made in
patients of the control group other than the routine antiemetic therapy. The data
of the study were collected by using a questionnaire and nausea-vomiting chart.
Severity of nausea-vomiting was assessed by using the visual analog scale on this
chart. It was determined that the acupressure band applied to the patients
included in the study reduced number and severity of nausea-vomiting (P < .05);
however, the acupressure applied with pressure did not affect number and severity
of nausea-vomiting (P > .05). It was found that the acupressure band was
effective for reducing the chemotherapy-induced nausea and vomiting.
PMID- 27501208
TI - Incivility Across the Nursing Continuum.
AB - Incivility affects nurses throughout education and practice; it directly affects
patient safety as well as nurses' decisions to remain in academia and clinical
practice. This article reviews the current literature on incivility and proposes
the application of social learning theory to evidence-based strategies that can
be implemented to combat incivility.
PMID- 27501209
TI - Toward a Holistic Approach to Spiritual Health Care for People With
Schizophrenia.
AB - Medical and behavioral treatments are the predominant types of rehabilitation
services for people with schizophrenia. Spirituality in people with schizophrenia
remains poorly conceptualized, thereby limiting knowledge advancement in the area
of spiritual health care services. To provide a framework for better clinical and
research practices, we advocate a holistic approach to investigating spirituality
and its application in spiritual health care services of people with
schizophrenia.
PMID- 27501210
TI - Effect of Support Group Intervention Applied to the Caregivers of Individuals
With Heart Failure on Caregiver Outcomes.
AB - This study was conducted to evaluate the effectiveness of support group
intervention applied to the caregivers of individuals with heart failure on
caregiver outcomes. Quasi-experimental research was conducted with 69 caregivers
as control (n = 35) and intervention (n = 34) groups in the cardiology outpatient
clinic of a university hospital. The intervention group participated in support
group meetings structured according to the Neuman Systems Model, and the data
were collected from both the intervention and control groups before the
intervention and 3 and 6 months later. Caregivers in the intervention group had
significantly lower burden scores compared with the control group in all
subdimensions except objective personal care, in terms of the group * time
interaction in a statistical way (P < .05). Caregivers in the intervention and
control groups had similar scores of depression symptoms (P > .05). The burden of
caregivers in the intervention group showed a statistically significant decrease
compared with the preintervention in all dimensions at 3 months. Thus, it is
suggested to extend the support group interventions for caregivers of patients
with heart failure and conduct these interventions in a longer period.
PMID- 27501211
TI - Effectiveness of Acupressure in Promoting Sleep Quality: A Systematic Review of
Randomized Controlled Trials.
AB - This review aimed to evaluate the effectiveness of acupressure in promoting sleep
quality among adults. Study findings included in the review showed that
acupressure significantly improved sleep quality compared with the control group,
but no superior effect of acupressure was found compared with sham acupressure.
PMID- 27501212
TI - Effect of Reflexology to Depressive Symptoms in Women With Overactive Bladder.
AB - This study is to determine the effect of foot reflexology on the level of
depression in women with OAB. Study findings included in the study showed foot
reflexology as a part of OAB treatment relieved urinary and depressive symptoms
and had a positive effect on quality of life.
PMID- 27501213
TI - Allergic Rhinitis: A Proprietary Extract of Pinus pinaster Aiton (Pycnogenol) Is
Found to Improve the Symptoms Associated With Allergic Rhinitis.
PMID- 27501214
TI - Health Literacy and Its Influence on Self-care Potential.
PMID- 27501215
TI - Detection of folate receptor-positive circulating tumor cells by ligand-targeted
polymerase chain reaction in non-small cell lung cancer patients.
PMID- 27501216
TI - Far-Field Super-resolution Detection of Plasmonic Near-Fields.
AB - We demonstrate a far-field single molecule super-resolution method that maps
plasmonic near-fields. The method is largely invariant to fluorescence quenching
(arising from probe proximity to a metal), has reduced point-spread-function
distortion compared to fluorescent dyes (arising from strong coupling to
nanoscopic metallic features), and has a large dynamic range (of 2 orders of
magnitude) allowing mapping of plasmonic field-enhancements regions. The method
takes advantage of the sensitivity of quantum dot (QD) stochastic blinking to
plasmonic near-fields. The modulation of the blinking characteristics thus
provides an indirect measure of the local field strength. Since QD blinking can
be monitored in the far-field, the method can measure localized plasmonic near
fields at high throughput using a simple far-field optical setup. Using this
method, propagation lengths and penetration depths were mapped-out for silver
nanowires of different diameters and for different dielectric environments, with
a spatial accuracy of ~15 nm. We initially use sparse sampling to ensure single
molecule localization for accurate characterization of the plasmonic near-field
with plans to increase density of emitters in further studies. The measured
propagation lengths and penetration depths values agree well with Maxwell finite
difference time-domain calculations and with published literature values. This
method offers advantages such as low cost, high throughput, and superresolved
mapping of localized plasmonic fields at high sensitivity and fidelity.
PMID- 27501217
TI - SOx Tolerant Pt/TiO2 Catalysts for CO Oxidation and the Effect of TiO2 Supports
on Catalytic Activity.
AB - We developed a new technique for mitigating catalyst deactivation caused by SO2
in exhaust gases. A series of 0.1 wt %-Pt/TiO2 catalysts with different surface,
crystal, and pore structures were prepared and tested for CO oxidation activity
in the presence of SO2 and H2O. The order of the CO oxidation activity under the
influence of SO2 was much different from that in the absence of SO2. Catalysts
with a high ratio of larger pores exhibited higher catalytic activity under the
influence of SO2 and H2O in the temperature range of 250-300 degrees C, whereas
other parameters, such as BET surface area and crystal structure of the TiO2
support, had minor effects on the CO oxidation activity. The oxidation state of
Pt differed significantly depending on the kind of TiO2 support. Some catalysts
were less active without H2 reduction pretreatment due to the presence of
oxidized Pt species.
PMID- 27501218
TI - Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves
Downstream Analysis of Target Cells.
AB - The use of in vitro cell line models for cancer research has been a useful tool.
However, it has been shown that these models fail to reliably mimic patient
tumors in different assays(1). Human tumor xenografts represent the gold standard
with respect to tumor biology, drug discovery, and metastasis research (2-4).
Tumor xenografts can be derived from different types of material like tumor cell
lines, tumor tissue from primary patient tumors(4) or serially transplanted
tumors. When propagated in vivo, xenografted tissue is infiltrated and
vascularized by cells of mouse origin. Multiple factors such as the tumor entity,
the origin of xenografted material, growth rate and region of transplantation
influence the composition and the amount of mouse cells present in tumor
xenografts. However, even when these factors are kept constant, the degree of
mouse cell contamination is highly variable. Contaminating mouse cells
significantly impair downstream analyses of human tumor xenografts. As mouse
fibroblasts show high plating efficacies and proliferation rates, they tend to
overgrow cultures of human tumor cells, especially slowly proliferating
subpopulations. Mouse cell derived DNA, mRNA, and protein components can bias
downstream gene expression analysis, next-generation sequencing, as well as
proteome analysis (5). To overcome these limitations, we have developed a fast
and easy method to isolate untouched human tumor cells from xenografted tumor
tissue. This procedure is based on the comprehensive depletion of cells of mouse
origin by combining automated tissue dissociation with the benchtop tissue
dissociator and magnetic cell sorting. Here, we demonstrate that human target
cells can be can be obtained with purities higher than 96% within less than 20
min independent of the tumor type.
PMID- 27501219
TI - Infertile men's needs and assessment of fertility care.
AB - INTRODUCTION: Male infertility is potentially a severe, low-control stressor.
There is limited knowledge of the expectations, needs, and assessment of
fertility care among men with severe infertility. The aim of this study was to
explore experience, expectations, needs, and assessment of fertility care among
Danish men having severe male-factor infertility. METHODS: Semi-structured
qualitative interview study with 10 men with very low sperm quality initiating
intracytoplasmic sperm injection (ICSI) treatment at the Fertility Clinic,
Copenhagen University Hospital, Hvidovre, Denmark. Five of the men participated
in a follow-up interview after their first ICSI treatment. The data collection
took place during November 2014 to May 2015. Data were analysed using qualitative
content analysis. RESULTS: Two themes were found: 'The maze' and 'Desire for
care'. It felt like an eternity for the men from the referral until treatment
started. The men did not understand the process, and it was like being in a maze.
The men saw fatherhood as something to strive for. They felt that they could not
do what a man is supposed to do, and they felt pushed aside and that treatment
focused on the women. The men appreciated the staff's kindness and
professionalism but desired the staff to address emotional subjects too.
CONCLUSION: The process from referral to treatment felt like a maze for these
men. They needed the staff to give them the opportunity to speak of the
psychosocial consequences of severe male-factor infertility.
PMID- 27501220
TI - Direct and indirect effects of parenting practices on socio-moral approval of
aggression in Polish young adults. Do all practices matter?
AB - The purpose of this article was to determine the socialisation antecedents of
socio-moral approval of aggression (SMAA). In Study 1, we assessed factorial
structure and reliability of the SMAA with a sample of 355 students who reported
on the extent to which they approved of six forms of aggressive behaviour and six
justifications of aggression. Two-factor solutions were obtained with regard to
forms and justifications of aggressive acts. Thus, approval of extreme and minor
aggression was distinguished as well as legitimate and illegitimate
justifications of aggression. In Study 2, we tested the path models of the
socialisation antecedents that contributed to the high approval of minor and
extreme aggressive acts as well as legitimate and illegitimate justifications of
aggression. Data were collected from 173 undergraduate students. Path analyses
showed that high levels of approval of extremely aggressive acts and of
illegitimate justifications of aggression were preceded by a sequence of negative
life events, beginning with frequent misbehaviour in childhood, corporal
punishment used by parents and ending with delinquency in adolescence. The
approval of minor aggression had little relation to socialisation factors apart
from a detrimental effect of psychological aggression while approval of
legitimate justifications of aggression had no socialisation antecedents.
PMID- 27501221
TI - Modeling Myotonic Dystrophy 1 in C2C12 Myoblast Cells.
AB - Myotonic dystrophy 1 (DM1) is a common form of muscular dystrophy. Although
several animal models have been established for DM1, myoblast cell models are
still important because they offer an efficient cellular alternative for studying
cellular and molecular events. Though C2C12 myoblast cells have been widely used
to study myogenesis, resistance to gene transfection, or viral transduction,
hinders research in C2C12 cells. Here, we describe an optimized protocol that
includes daily maintenance, transfection and transduction procedures to introduce
genes into C2C12 myoblasts and the induction of myocyte differentiation.
Collectively, these procedures enable best transfection/transduction
efficiencies, as well as consistent differentiation outcomes. The protocol
described in establishing DM1 myoblast cell models would benefit the study of
myotonic dystrophy, as well as other muscular diseases.
PMID- 27501222
TI - A Joint Leap into a Future of High-Quality Simulation Research-Standardizing the
Reporting of Simulation Science.
PMID- 27501224
TI - Cutaneous T-Cell Lymphoma. A hypothesis on disease pathophysiology involving
deficiency in DNA repair.
AB - Cutaneous T-cell lymphoma (CTCL) is a rare disease occurring in Europe among two
persons per million per year. It affects men more often than women (2:1). It is
primarily a skin disease. In about 20% of patients, it becomes fatal with tumours
in the skin and spreading to lymph glands. Approximately 3% of patients show a
leukemic form called Sezary's syndrome, where malignant cells are present in
blood with accompanying erythrodermia. CTCL is a T-lymphocyte disease occurring
late in life as the average age of patients is around 66 years in Europe, Japan
and the US. This article focuses on cell lines and immune surveillance in CTCL,
and especially the pronounced chromosomal instability. It leads to the hypothesis
that chromosomal changes is the key event linked to DNA repair deficiencies,
which in a subpopulation of T cells leads to CTCL development over years.
PMID- 27501226
TI - Hypoxia-preconditioned allogeneic mesenchymal stem cells can be used for
myocardial repair in non-human primates.
PMID- 27501225
TI - Naming influences 9-month-olds' identification of discrete categories along a
perceptual continuum.
AB - A growing body of evidence documents that naming guides 9-month-old infants as
they organize their visual experiences into categories. In particular, this
evidence reveals that naming highlights categories when these are visually
distinct. Here we advance this work in by introducing an anticipatory looking
design to assess how naming influences infants' categorization of objects that
vary along a perceptual continuum. We introduced 9-month-old infants (n = 48) to
continua of novel creature-like objects. During the learning phase, infants had
an opportunity to observe that objects from one end of the perceptual continuum
moved to the left and objects from the other end moved to the right. What varied
was how the objects were named. Infants in theone-name condition heard the same
novel noun applied to all objects along the continuum; those in the two-name
condition heard one name for objects from one end of the continuum and a second
name for objects at the other end. At test, all infants viewed new objects from
the same continuum. At issue was whether infants would anticipate the side to
which the test objects would move and whether their expectations varied as a
function of naming condition. Infants in the one-name condition formed a single
overarching category and therefore searched for new test objects at either
location; those in the two-name condition discerned two categories and therefore
correctly anticipated the likely location of the test objects, whether these were
close to the poles or to the center of the continuum. This provides the first
evidence that by 9 months, naming supports both the number of categories infants
impose along a perceptual continuum and the clarity of the category boundaries.
PMID- 27501227
TI - HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral
Function of GPCR Heteromers in Mice.
AB - The heteromeric receptor complex between 5-HT2A and mGlu2 has been implicated in
some of the behavioral phenotypes in mouse models of psychosis(1,2).
Consequently, investigation of structural details of the interaction between 5
HT2A and mGlu2 affecting schizophrenia-related behaviors represents a powerful
translational tool. As previously shown, the head-twitch response (HTR) in mice
is elicited by hallucinogenic drugs and this behavioral response is absent in 5
HT2A knockout (KO) mice(3,4). Additionally, by conditionally expressing the 5
HT2A receptor only in cortex, it was demonstrated that 5-HT2A receptor-dependent
signaling pathways on cortical pyramidal neurons are sufficient to elicit head
twitch behavior in response to hallucinogenic drugs(3). Finally, it has been
shown that the head-twitch behavioral response induced by the hallucinogens DOI
and lysergic acid diethylamide (LSD) is significantly decreased in mGlu2-KO
mice(5). These findings suggest that mGlu2 is at least in part necessary for the
5-HT2A receptor-dependent psychosis-like behavioral effects induced by LSD-like
drugs. However, this does not provide evidence as to whether the 5-HT2A-mGlu2
receptor complex is necessary for this behavioral phenotype. To address this
question, herpes simplex virus (HSV) constructs to express either mGlu2 or
mGlu2DeltaTM4N (mGlu2/mGlu3 chimeric construct that does not form the 5-HT2A
mGlu2 receptor complex) in the frontal cortex of mGlu2-KO mice were used to
examine whether this GPCR heteromeric complex is needed for the behavioral
effects induced by LSD-like drugs(6).
PMID- 27501228
TI - Predicting the dynamic impact behaviour of spray droplets on flat plant surfaces.
AB - The dynamic impact behaviour of water droplets on plant surfaces was investigated
based on a multiphase computational fluid dynamics (CFD) model. The study was
conducted using the Volume Of Fluid (VOF) approach. The static contact angle of
water droplets on leaf surfaces of different plants (apple, pear, leek and
cabbage) was measured and found to vary between 54.9 and 138.2 degrees . Impact
experiments were conducted by monitoring the flow and impact characteristics of
water droplets on leaves in still air with a high speed camera. Droplets were
generated by an agricultural flat fan spray nozzle moving across the leaf at
constant speed. The nozzle produced droplets with diameters ranging from 20.6 up
to 550.8 MUm, and droplet velocity values near the impact between 0.03 and 13.2 m
s(-1). The CFD model was capable of predicting the observed dynamic impact
behaviour of droplets on the plant surfaces. The fate of the droplets after the
impact process for adhesion, bouncing or splashing was accurately predicted for
Weber numbers (We) in the range of 0.007 to 1096 and droplet Reynolds numbers
(Re) between 5 to 8000. The process was highly dependent on the surface and
droplet flow characteristics during the impact. Combinations of We, Re and
Ohnesorge (Oh) numbers defined the droplet maximum spread factor, the number of
secondary droplets generated as a result of the splashing process and the
transition between the different impact outcomes. These criteria can then be used
in field scale spray deposition and drift models to better understand
agricultural spray operations.
PMID- 27501230
TI - Stereoselective Construction of Spiro-Fused Tricyclic Frameworks by Sequential
Reaction of Enynes, Imines, and Diazoalkenes with Rh(I) and Rh(II) Catalysts.
AB - Stereoselective construction of spiro-fused tricyclic compounds from enynes
having a tethered imine with diazoalkenes was achieved by Rh(I)- and Rh(II)
catalyzed sequential reactions. This method consists of three reactions, i.e.,
Rh(I)-catalyzed cyclization of enynes with a tethered imine, Rh(II)-catalyzed
cyclopropanation with diazoalkenes, and Cope rearrangement. Notably, the
sequential reactions can be operated in one pot, in which Rh(I) and Rh(II)
catalysts work in relay without any serious catalyst deactivation to afford the
spirocycles in a stereoselective manner.
PMID- 27501229
TI - Genomic Alteration in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines
Inferred from Karyotyping, Molecular Cytogenetics, and Array Comparative Genomic
Hybridization.
AB - Genomic alteration in head and neck squamous cell carcinoma (HNSCC) was studied
in two cell line pairs (HN30-HN31 and HN4-HN12) using conventional C-banding,
multiplex fluorescence in situ hybridization (M-FISH), and array comparative
genomic hybridization (array CGH). HN30 and HN4 were derived from primary lesions
in the pharynx and base of tongue, respectively, and HN31 and HN12 were derived
from lymph-node metastatic lesions belonging to the same patients. Gain of
chromosome 1, 7, and 11 were shared in almost all cell lines. Hierarchical
clustering revealed that HN31 was closely related to HN4, which shared eight
chromosome alteration cases. Large C-positive heterochromatins were found in the
centromeric region of chromosome 9 in HN31 and HN4, which suggests complex
structural amplification of the repetitive sequence. Array CGH revealed
amplification of 7p22.3p11.2, 8q11.23q12.1, and 14q32.33 in all cell lines
involved with tumorigenesis and inflammation genes. The amplification of 2p21
(SIX3), 11p15.5 (H19), and 11q21q22.3 (MAML2, PGR, TRPC6, and MMP family)
regions, and deletion of 9p23 (PTPRD) and 16q23.1 (WWOX) regions were identified
in HN31 and HN12. Interestingly, partial loss of PTPRD (9p23) and WWOX (16q23.1)
genes was identified in HN31 and HN12, and the level of gene expression tended to
be the down-regulation of PTPRD, with no detectable expression of the WWOX gene.
This suggests that the scarcity of PTPRD and WWOX genes might have played an
important role in progression of HNSCC, and could be considered as a target for
cancer therapy or a biomarker in molecular pathology.
PMID- 27501231
TI - Event Recognition Based on Deep Learning in Chinese Texts.
AB - Event recognition is the most fundamental and critical task in event-based
natural language processing systems. Existing event recognition methods based on
rules and shallow neural networks have certain limitations. For example,
extracting features using methods based on rules is difficult; methods based on
shallow neural networks converge too quickly to a local minimum, resulting in low
recognition precision. To address these problems, we propose the Chinese
emergency event recognition model based on deep learning (CEERM). Firstly, we use
a word segmentation system to segment sentences. According to event elements
labeled in the CEC 2.0 corpus, we classify words into five categories: trigger
words, participants, objects, time and location. Each word is vectorized
according to the following six feature layers: part of speech, dependency
grammar, length, location, distance between trigger word and core word and
trigger word frequency. We obtain deep semantic features of words by training a
feature vector set using a deep belief network (DBN), then analyze those features
in order to identify trigger words by means of a back propagation neural network.
Extensive testing shows that the CEERM achieves excellent recognition
performance, with a maximum F-measure value of 85.17%. Moreover, we propose the
dynamic-supervised DBN, which adds supervised fine-tuning to a restricted
Boltzmann machine layer by monitoring its training performance. Test analysis
reveals that the new DBN improves recognition performance and effectively
controls the training time. Although the F-measure increases to 88.11%, the
training time increases by only 25.35%.
PMID- 27501232
TI - Quality effects of using organogels in breakfast sausage.
AB - Organogels made with canola oil, ethyl cellulose (EC; 8, 10, 12 and 14%), and
sorbitan monostearate (SMS; 1.5, 3.0%) were used to replace pork fat in breakfast
sausages. Some of the formulations with SMS matched the objective hardness
(texture analyzer) of the pork fat control; however, sensory hardness was not so
easily matched. Using canola oil by itself resulted in lower objective and
subjective hardness values than the control. Sensory cohesiveness was not
affected by the replacements, but springiness was lower in the treatments without
SMS and some of the high EC treatments with SMS. Lightness of organogel
treatments was lower than the control, but redness and yellowness values were not
affected. Sensory juiciness and oiliness were in general lower in the organogel
treatments. Overall, the study demonstrates the potential for the use of
organogels in coarse ground meat products, as a means of improving the
nutritional profile by replacing saturated fat with mono and poly unsaturated
oils.
PMID- 27501233
TI - Inter-laboratory assessment by trained panelists from France and the United
Kingdom of beef cooked at two different end-point temperatures.
AB - Eating quality of the same meat samples from different animal types cooked at two
end-point cooking temperatures (55 degrees C and 74 degrees C) was evaluated by
trained panels in France and the United Kingdom. Tenderness and juiciness scores
were greater at 55 degrees C than at 74 degrees C, irrespective of the animal
type and location of the panel. The UK panel, independently of animal type, gave
greater scores for beef flavour (+7 to +24%, P<0.001) but lower scores for
abnormal flavour (-10 to -17%, P<0.001) at 74 degrees C. Abnormal flavour score
by the French panel was higher at 74 degrees C than at 55 degrees C (+26%,
P<0.001). Irrespective of the data set, tenderness was correlated with juiciness
and beef flavour. Overall, this study found that cooking beef at a lower
temperature increased tenderness and juiciness, irrespective of the location of
the panel. In contrast, cooking beef at higher temperatures increased beef
flavour and decreased abnormal flavour for the UK panelists but increased
abnormal flavour for the French panel.
PMID- 27501234
TI - Quantification of soy protein using the isotope method (delta(13)C and
delta(15)N) for commercial brands of beef hamburger.
AB - Hamburgers (beef patties) may be adulterated through the overuse of protein
extenders. Among vegetables, soy protein is the best substitute for animal
protein. These ingredients help to reduce the cost of producing a final product,
and they maximize profits for fraudulent industries. Moreover, the ingestion of
soy or other non-meat proteins by allergic individuals may present a health risk.
In addition, monitoring by supervisory bodies is hampered by a lack of
appropriate analytical methodologies. Within this context, the aim of this study
was to determine and quantify the levels of added soy protein by determination of
(15)N and (13)C stable isotopes. A total of 100 beef hamburger samples from 10
commercial brands were analyzed. Only three samples of the G brand were within
the standards set the Brazilian legislation. The remaining 97 samples from 10
commercial brands contained >4% soy protein; therefore, they are adulterated and
not in compliance with the current legislation.
PMID- 27501235
TI - Mice Expressing a "Hyper-Sensitive" Form of the Cannabinoid Receptor 1 (CB1) Are
Neither Obese Nor Diabetic.
AB - Multiple lines of evidence implicate the endocannabinoid signaling system in the
modulation of metabolic disease. Genetic or pharmacological inactivation of CB1
in rodents leads to reduced body weight, resistance to diet-induced obesity,
decreased intake of highly palatable food, and increased energy expenditure.
Cannabinoid agonists stimulate feeding in rodents and increased levels of
endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that
sustained endocannabinoid signaling can lead to obesity and diabetes was examined
in this study using S426A/S430A mutant mice expressing a desensitization
resistant CB1 receptor. These mice display exaggerated and prolonged responses to
acute administration of phytocannabinoids, synthetic cannabinoids, and
endocannabinoids. As a consequence these mice represent a novel model for
determining the effect of enhanced endocannabinoid signaling on metabolic
disease. S426A/S430A mutants consumed equivalent amounts of both high fat (45%)
and low fat (10%) chow control diet compared to wild-type littermate controls.
S426A/S430A mutants and wild-type mice fed either high or low fat control diet
displayed similar fasting blood glucose levels and normal glucose clearance
following a 2 g/kg glucose challenge. Furthermore, S426A/S430A mutants and wild
type mice consumed similar amounts of chow following an overnight fast. While
both THC and JZL195 significantly increased food intake two hours after
injection, this increase was similar between the S426A/S430A mutant and wildtype
control mice Our results indicate that S426A/S430A mutant mice expressing the
desensitization-resistant form of CB1 do not exhibit differences in body weight,
food intake, glucose homeostasis, or re-feeding following a fast.
PMID- 27501236
TI - Paediatric primary cutaneous marginal zone B-cell lymphoma: does it differ from
its adult counterpart?
AB - BACKGROUND: Primary cutaneous marginal zone B-cell lymphoma (PCMZL) has rarely
been reported in patients younger than 20 years. OBJECTIVES: To report our
experience with PCMZL in the paediatric/adolescent age group. METHODS: Medical
records of patients diagnosed with PCMZL before age 20 years and managed at two
cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were
reviewed. RESULTS: The study group included 11 patients (six girls; median age 16
years, range 6-19.5); 10 had generalized/multifocal (T3) and one had
regional/localized (T2) disease. Lesions were located on the limbs in all
patients and the trunk in six; two had facial lesions. Staging in all but one was
based on whole-body computed tomography or positron emission tomography. Initial
management in most patients included nonradiation modalities: one patient with
localized disease received intralesional steroids; six patients with multifocal
disease received the following: topical/intralesional steroids (n = 3); excision
(n = 2); 'watch and wait' (n = 1). No extracutaneous progression was noted during
a median follow-up of 5.5 years (mean 7.5, range 0.5-14). At present, five
patients are in complete remission. CONCLUSIONS: Based on our data (largest
series in the literature with the longest follow-up), the clinicopathological
presentation and course of PCMZL in the paediatric/adolescent age group are
similar to those in adults. Given the indolent course and the long life
expectancy of these young patients, the cumulative risk of imaging studies and
the age-related potential toxicity of treatment, especially radiation, should be
taken into consideration.
PMID- 27501237
TI - Improving survival of patients with locally advanced non-small-cell cancer
remains a challenge: comment to PROCLAIM.
PMID- 27501238
TI - Sexual dysfunction in women with Parkinson's disease.
AB - BACKGROUND: Sexual dysfunction in women with Parkinson's disease is poorly
understood and research in this area is scarce. The objectives of this study were
sexual function characterization in female Parkinson's disease patients,
description of sexual dysfunctions, correlation with disease characteristics, and
comparison with matched healthy controls. METHODS: Social and demographic data
from consecutive female patients with Parkinson's disease and matched healthy
controls were collected. The following instruments were used: UPDRS, the Hoehn
and Yahr scale, the Beck Depression Inventory-II, the Female Sexual Function
Index, and the Sexual Dysfunction Inventory. The only exclusion criterion was
cognitive deterioration precluding comprehension of the study scope and its
instruments. RESULTS: Of the 95 patients identified, 61 were included. Mean age
was 66 years (range 40-89 years), and mean disease duration was seven years
(range 1-18 years). Twenty-nine presented an akinetic-rigid syndrome, 25 tremoric
disease, and, the remaining, a mixed type of disease. Mean "on" total/part III
UPDRS scores were 46 +/- 15.0 and 31 +/- 8.9. Sexual dysfunction was present in
86.9% of patients and 79.0% of controls, according to the Female Sexual Function
Index (p < .01), and in 57.4% of patients and 22.6% of controls, according to the
Sexual Dysfunction Inventory (p < .001). Multivariate binary logistic regression
identified age and depressive symptoms as positive predictors in the severity of
sexual dysfunction. Disease duration, UPDRS part III score, Hoehn and Yahr stage,
and antiparkinsonian medication did not show significant predictive value.
CONCLUSIONS: Sexual dysfunction is more prevalent in women with Parkinson's
disease than in controls and is predicted by older age and severity of depressive
symptoms. (c) 2016 International Parkinson and Movement Disorder Society.
PMID- 27501239
TI - The agar microdilution method - a new method for antimicrobial susceptibility
testing for essential oils and plant extracts.
AB - AIMS: To develop a new agar microdilution technique suitable for the assessment
of the antimicrobial activity of natural plant products such as essential oils or
plant extracts as well as to evaluate the antimicrobial effect of several
essential oils and plant extracts. METHODS AND RESULTS: The proposed agar
microdilution method was evolved on the basis of the CLSI agar dilution method,
approved for conventional antimicrobials. However, this new method combines
convenience and time/cost effectiveness typical for microtitre methods with the
advantages of the agar dilution of hydrophobic or coloured substances. Different
concentrations of the tested agents were added to Eppendorf tubes with molten
Mueller-Hinton agar, vortexed and dispensed into the 96-well microplate in a
small volume of 100 MUl per well which allows for rapid, easy and economical
preparation of samples as well as providing a uniform and stable dispersion
without separation of the oil-water phases which occurs in methods with liquid
medium. Next, the agar microdilution plates were inoculated with four reference
bacterial strains. The results of our study demonstrated that the minimal
inhibitory concentrations (MICs) were successfully determined using the agar
microdilution method even with hydrophobic essential oils or strongly coloured
plant extracts. CONCLUSIONS: The new agar microdilution method avoids the
problems associated with testing of water insoluble, oily or strongly coloured
plant natural products. Moreover, it enables the reliable, cheap and easy MIC
determination of such agents. SIGNIFICANCE AND IMPACT OF THE STUDY: In the era of
increasing antibiotic resistance high hopes are associated with new drugs of
plant origin. However, the lack of standardized and reliable testing methods for
assessing antibacterial activity of plant natural products causes impediment to
research into this area. This study demonstrated that the agar microdilution
method can be used successfully for testing oily and coloured substances.
PMID- 27501240
TI - Diffusion in Colocation Contact Networks: The Impact of Nodal Spatiotemporal
Dynamics.
AB - Temporal contact networks are studied to understand dynamic spreading phenomena
such as communicable diseases or information dissemination. To establish how
spatiotemporal dynamics of nodes impact spreading potential in colocation contact
networks, we propose "inducement-shuffling" null models which break one or more
correlations between times, locations and nodes. By reconfiguring the time and/or
location of each node's presence in the network, these models induce alternative
sets of colocation events giving rise to contact networks with varying spreading
potential. This enables second-order causal reasoning about how correlations in
nodes' spatiotemporal preferences not only lead to a given contact network but
ultimately influence the network's spreading potential. We find the correlation
between nodes and times to be the greatest impediment to spreading, while the
correlation between times and locations slightly catalyzes spreading. Under each
of the presented null models we measure both the number of contacts and infection
prevalence as a function of time, with the surprising finding that the two have
no direct causality.
PMID- 27501241
TI - Establishment of 3D Co-Culture Models from Different Stages of Human Tongue
Tumorigenesis: Utility in Understanding Neoplastic Progression.
AB - To study multistep tumorigenesis process, there is a need of in-vitro 3D model
simulating in-vivo tissue. Present study aimed to reconstitute in-vitro tissue
models comprising various stages of neoplastic progression of tongue
tumorigenesis and to evaluate the utility of these models to investigate the role
of stromal fibroblasts in maintenance of desmosomal anchoring junctions using
transmission electron microscopy. We reconstituted in-vitro models representing
normal, dysplastic, and malignant tissues by seeding primary keratinocytes on
either fibroblast embedded in collagen matrix or plain collagen matrix in growth
factor-free medium. The findings of histomorphometry, immunohistochemistry, and
electron microscopy analyses of the three types of 3D cultures showed that the
stratified growth, cell proliferation, and differentiation were comparable
between co-cultures and their respective native tissues; however, they largely
differed in cultures grown without fibroblasts. The immunostaining intensity of
proteins, viz., desmoplakin, desmoglein, and plakoglobin, was reduced as the
disease stage increased in all co-cultures as observed in respective native
tissues. Desmosome-like structures were identified using immunogold labeling in
these cultures. Moreover, electron microscopic observations revealed that the
desmosome number and their length were significantly reduced and intercellular
spaces were increased in cultures grown without fibroblasts when compared with
their co-culture counterparts. Our results showed that the major steps of tongue
tumorigenesis can be reproduced in-vitro. Stromal fibroblasts play a role in
regulation of epithelial thickness, cell proliferation, differentiation, and
maintenance of desmosomalanchoring junctions in in-vitro grown tissues. The
reconstituted co-culture models could help to answer various biological questions
especially related to tongue tumorigenesis.
PMID- 27501243
TI - New clinical criteria for septic shock: serum lactate level as new emerging vital
sign.
PMID- 27501242
TI - Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard
for Validating Non-Invasive Liver Fat Fraction Measurements by MRI.
AB - BACKGROUND AND AIMS: Validation of non-invasive methods of liver fat
quantification requires a reference standard. However, using standard
histopathology assessment of liver biopsies is problematical because of poor
repeatability. We aimed to assess a stereological method of measuring volumetric
liver fat fraction (VLFF) in liver biopsies and to use the method to validate a
magnetic resonance imaging method for measurement of VLFF. METHODS: VLFFs were
measured in 59 subjects (1) by three independent analysts using a stereological
point counting technique combined with the Delesse principle on liver biopsy
histological sections and (2) by three independent analysts using the HepaFat
Scan(r) technique on magnetic resonance images of the liver. Bland Altman
statistics and intraclass correlation (IC) were used to assess the repeatability
of each method and the bias between the methods of liver fat fraction
measurement. RESULTS: Inter-analyst repeatability coefficients for the stereology
and HepaFat-Scan(r) methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)%
VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI
0.985-0.994) respectively. Small biases (<=3.4%) were observable between two
pairs of analysts using stereology while no significant biases were observable
between any of the three pairs of analysts using HepaFat-Scan(r). A bias of 1.4+/
0.5% VLFF was observed between the HepaFat-Scan(r) method and the stereological
method. CONCLUSIONS: Repeatability of the stereological method is superior to the
previously reported performance of assessment of hepatic steatosis by
histopathologists and is a suitable reference standard for validating non
invasive methods of measurement of VLFF.
PMID- 27501244
TI - 2015 Philip S. Portoghese Medicinal Chemistry Lectureship. Curing Hepatitis C
Virus Infection with Direct-Acting Antiviral Agents: The Arc of a Medicinal
Chemistry Triumph.
AB - The development of direct-acting antiviral agents that can cure a chronic
hepatitis C virus (HCV) infection after 8-12 weeks of daily, well-tolerated
therapy has revolutionized the treatment of this insidious disease. In this
article, three of Bristol-Myers Squibb's HCV programs are summarized, each of
which produced a clinical candidate: the NS3 protease inhibitor asunaprevir (64),
marketed as Sunvepra, the NS5A replication complex inhibitor daclatasvir (117),
marketed as Daklinza, and the allosteric NS5B polymerase inhibitor beclabuvir
(142), which is in late stage clinical studies. A clinical study with 64 and 117
established for the first time that a chronic HCV infection could be cured by
treatment with direct-acting antiviral agents alone in the absence of interferon.
The development of small molecule HCV therapeutics, designed by medicinal
chemists, has been hailed as "the arc of a medical triumph" but may equally well
be described as "the arc of a medicinal chemistry triumph".
PMID- 27501245
TI - Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection.
AB - During chronic viral infection, virus-specific CD8(+) T cells become exhausted,
exhibit poor effector function and lose memory potential. However, exhausted
CD8(+) T cells can still contain viral replication in chronic infections,
although the mechanism of this containment is largely unknown. Here we show that
a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has
a critical role in the control of viral replication in mice that were chronically
infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5(+) CD8(+) T
cells were able to migrate into B-cell follicles, expressed lower levels of
inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5(-)
[corrected] subset. Furthermore, we identified the Id2-E2A signalling axis as an
important regulator of the generation of this subset. In patients with HIV, we
also identified a virus-specific CXCR5(+) CD8(+) T-cell subset, and its number
was inversely correlated with viral load. The CXCR5(+) subset showed greater
therapeutic potential than the CXCR5(-) [corrected] subset when adoptively
transferred to chronically infected mice, and exhibited synergistic reduction of
viral load when combined with anti-PD-L1 treatment. This study defines a unique
subset of exhausted CD8(+) T cells that has a pivotal role in the control of
viral replication during chronic viral infection.
PMID- 27501246
TI - Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping
sickness.
AB - Chagas disease, leishmaniasis and sleeping sickness affect 20 million people
worldwide and lead to more than 50,000 deaths annually. The diseases are caused
by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp.
and Trypanosoma brucei spp., respectively. These parasites have similar biology
and genomic sequence, suggesting that all three diseases could be cured with
drugs that modulate the activity of a conserved parasite target. However, no such
molecular targets or broad spectrum drugs have been identified to date. Here we
describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with
unprecedented in vivo efficacy, which cleared parasites from mice in all three
models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non
competitive mechanism, does not inhibit the mammalian proteasome or growth of
mammalian cells, and is well-tolerated in mice. Our data provide genetic and
chemical validation of the parasite proteasome as a promising therapeutic target
for treatment of kinetoplastid infections, and underscore the possibility of
developing a single class of drugs for these neglected diseases.
PMID- 27501247
TI - Germinal centre hypoxia and regulation of antibody qualities by a hypoxia
response system.
AB - Germinal centres (GCs) promote humoral immunity and vaccine efficacy. In GCs,
antigen-activated B cells proliferate, express high-affinity antibodies, promote
antibody class switching, and yield B cell memory. Whereas the cytokine milieu
has long been known to regulate effector functions that include the choice of
immunoglobulin class, both cell-autonomous and extrinsic metabolic programming
have emerged as modulators of T-cell-mediated immunity. Here we show in mice that
GC light zones are hypoxic, and that low oxygen tension () alters B cell
physiology and function. In addition to reduced proliferation and increased B
cell death, low impairs antibody class switching to the pro-inflammatory IgG2c
antibody isotype by limiting the expression of activation-induced cytosine
deaminase (AID). Hypoxia induces HIF transcription factors by restricting the
activity of prolyl hydroxyl dioxygenase enzymes, which hydroxylate HIF-1alpha and
HIF-2alpha to destabilize HIF by binding the von Hippel-Landau tumour suppressor
protein (pVHL). B-cell-specific depletion of pVHL leads to constitutive HIF
stabilization, decreases antigen-specific GC B cells and undermines the
generation of high-affinity IgG, switching to IgG2c, early memory B cells, and
recall antibody responses. HIF induction can reprogram metabolic and growth
factor gene expression. Sustained hypoxia or HIF induction by pVHL deficiency
inhibits mTOR complex 1 (mTORC1) activity in B lymphoblasts, and mTORC1
haploinsufficient B cells have reduced clonal expansion, AID expression, and
capacities to yield IgG2c and high-affinity antibodies. Thus, the normal
physiology of GCs involves regional variegation of hypoxia, and HIF-dependent
oxygen sensing regulates vital functions of B cells. We propose that the
restriction of oxygen in lymphoid organs, which can be altered in
pathophysiological states, modulates humoral immunity.
PMID- 27501248
TI - Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy.
AB - Chronic viral infections are characterized by a state of CD8+ T-cell dysfunction
that is associated with expression of the programmed cell death 1 (PD-1)
inhibitory receptor. A better understanding of the mechanisms that regulate CD8+
T-cell responses during chronic infection is required to improve immunotherapies
that restore function in exhausted CD8+ T cells. Here we identify a population of
virus-specific CD8+ T cells that proliferate after blockade of the PD-1
inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis
virus (LCMV). These LCMV-specific CD8+ T cells expressed the PD-1 inhibitory
receptor, but also expressed several costimulatory molecules such as ICOS and
CD28. This CD8+ T-cell subset was characterized by a unique gene signature that
was related to that of CD4+ T follicular helper (TFH) cells, CD8+ T cell memory
precursors and haematopoietic stem cell progenitors, but that was distinct from
that of CD4+ TH1 cells and CD8+ terminal effectors. This CD8+ T-cell population
was found only in lymphoid tissues and resided predominantly in the T-cell zones
along with naive CD8+ T cells. These PD-1+CD8+ T cells resembled stem cells
during chronic LCMV infection, undergoing self-renewal and also differentiating
into the terminally exhausted CD8+ T cells that were present in both lymphoid and
non-lymphoid tissues. The proliferative burst after PD-1 blockade came almost
exclusively from this CD8+ T-cell subset. Notably, the transcription factor TCF1
had a cell-intrinsic and essential role in the generation of this CD8+ T-cell
subset. These findings provide a better understanding of T-cell exhaustion and
have implications in the optimization of PD-1-directed immunotherapy in chronic
infections and cancer.
PMID- 27501249
TI - Differential alpha-adrenergic modulation of rapid onset vasodilatation along
resistance networks of skeletal muscle in old versus young mice.
AB - KEY POINTS: Rapid onset vasodilatation (ROV) initiates functional hyperaemia upon
skeletal muscle contraction and is attenuated during ageing via alpha
adrenoreceptor (alphaAR) stimulation, but it is unknown where this effect
predominates in resistance networks. In gluteus maximus muscles of young (4
months) and old (24 months) male C57BL/6 mice, tetanic contraction while
observing feed arteries and arterioles initiated ROV, which increased with
contraction duration, peaked later in upstream versus downstream vessel branches
and was attenuated throughout networks with advanced age. With no effect on
muscle force production, inhibiting alphaARs improved ROV in old mice while
activating alphaARs attenuated ROV in young mice. Modulating ROV through alphaARs
was greater in upstream feed arteries and arterioles compared to downstream
arterioles, with alpha2 ARs more effective than alpha1 ARs. ROV is coordinated
along resistance networks and modulated differentially between young and old mice
via alphaARs; with advanced age, attenuated dilatation of upstream branches will
restrict muscle blood flow. ABSTRACT: Rapid onset vasodilatation (ROV) in
skeletal muscle is attenuated during advanced age via alpha-adrenoreceptor
(alphaAR) activation, but it is unknown where such effects predominate in the
resistance vasculature. Studying the gluteus maximus muscle (GM) of anaesthetized
young (4 months) and old (24 months) male C57BL/6 mice, we tested the hypothesis
that attenuation of ROV during advanced age is most effective in proximal
branches of microvascular resistance networks. Diameters of a feed artery (FA)
and first- (1A), second- (2A) and third- (3A) order arterioles were studied in
response to single tetanic contractions (100 Hz, 100-1000 ms). ROV began within 1
s and peaked sooner in 2A and 3A (~3 s) than in 1A or FA (~4 s). Relative
amplitudes of dilatation increased with contraction duration and with vessel
branch order (FA<1A<2A<3A). In old mice, attenuation of ROV was greater in FA and
1A compared to 2A and 3A. With no effect on muscle force production, inhibiting
alphaARs (phentolamine; 10-6 m) improved ROV in FA and 1A of old mice while
subthreshold stimulation of alphaARs in young mice (noradrenaline; 10-9 m)
depressed ROV most effectively in FA and 1A. In young mice, stimulating alpha1
ARs (phenylephrine; 10-7 m) and alpha2 ARs (UK 14304; 10-7 m) attenuated ROV
primarily in FA. In old mice, inhibiting alpha2 ARs (rauwolscine; 10-7 m)
restored ROV more effectively in FA and 1A than did inhibiting alpha1 ARs
(prazosin; 10-8 m). We conclude that, with temporal and spatial coordination
along resistance networks, attenuation of ROV with advanced age is most effective
in proximal branches via constitutive activation of alpha2 ARs.
PMID- 27501250
TI - Validation of a point-of-care prothrombin time test after cardiopulmonary bypass
in cardiac surgery.
AB - Point-of-care coagulation monitoring can be used for the guidance of haemostasis
management. However, the influence of time on point-of-care prothrombin time
testing following protamine administration after cardiopulmonary bypass has not
been investigated. Bland-Altman and error grid analysis were used to analyse the
level of agreement between prothrombin time measurements from point-of-care and
laboratory tests before cardiopulmonary bypass, and then 3 min, 6 min and 10 min
after protamine administration. Prothrombin times were expressed as International
Normalised Ratios. While the point-of-care and laboratory prothrombin time
measurements showed a high level of agreement before bypass, this agreement
deteriorated following protamine administration to a mean (SD) bias of -0.22
(0.13) [limits of agreement 0.48-0.04]. Error grid analysis revealed that 35
(70%) of the paired values showed a clinically relevant discrepancy in
international normalised ratio. At 3 min, 6 min and 10 min after cardiopulmonary
bypass there is a clinical unacceptable discrepancy between the point-of-care and
laboratory measurement of prothrombin time.
PMID- 27501252
TI - Chronic and low exposure to a pharmaceutical cocktail induces mitochondrial
dysfunction in liver and hyperglycemia: Differential responses between lean and
obese mice.
AB - Pharmaceuticals are found in the environment but the impact of this contamination
on human and animal health is poorly known. The liver could be particularly
targeted since a significant number of these drugs are hepatotoxic, in particular
via oxidative stress and mitochondrial dysfunction. Notably, the latter events
can also be observed in liver diseases linked to obesity, so that the obese liver
might be more sensitive to drug toxicity. In this study, we determined the
effects of a chronic exposure to low doses of pharmaceuticals in wild-type and
obese mice, with a particular focus on mitochondrial function. To this end, wild
type and ob/ob mice were exposed for 4 months to a cocktail of 11 pharmaceuticals
provided in drinking water containing 0.01, 0.1, or 1 mg/L of each drug. At the
end of the treatment, liver mitochondria were isolated and different parameters
were measured. Chronic exposure to the pharmaceuticals reduced mitochondrial
respiration driven by succinate and palmitoyl-l-carnitine in wild-type mice and
increased antimycin-induced ROS production in ob/ob mice. Hyperglycemia and
hepatic histological abnormalities were also observed in treated ob/ob mice.
Investigations were also carried out in isolated liver mitochondria incubated
with the mixture, or with each individual drug. The mitochondrial effects of the
mixture were different from those observed in treated mice and could not be
predicted from the results obtained with each drug. Because some of the 11 drugs
included in our cocktail can be found in water at relatively high concentrations,
our data could be relevant in environmental toxicology. (c) 2016 Wiley
Periodicals, Inc. Environ Toxicol 32: 1375-1389, 2017.
PMID- 27501253
TI - Downregulation of nucleophosmin expression inhibited proliferation and induced
apoptosis in salivary gland adenoid cystic carcinoma.
AB - BACKGROUND: This study aimed to explore the relationship between nucleophosmin
(NPM1) and patient clinical characteristics. Moreover, we investigated the effect
of NPM1 in tumor proliferation and apoptosis of salivary gland adenoid cystic
carcinoma (SACC). MATERIALS AND METHODS: NPM1 expression was examined in 74
specimens of SACC and 31 non-cancerous epithelium adjacent to carcinoma (NCEAC)
by immunohistochemistry (IHC). RNA interference technology was used to silence
NPM1 expression in SACC cells. We used transwell culture assay, cell counting kit
8 tests, and colony formation assay to test the proliferation, cisplatin
resistance, migration, and invasiveness of SACC cells. RESULTS: The nuclear and
cytoplasmic expression of NPM1 in SACC tissue was overexpressed and was tightly
linked to perineural invasion and lymph node metastasis. The downregulation of
NPM1 inhibited proliferation and induced apoptosis in SACC cells. Knockdown of
NPM1 expression had no effect on chemoresistance migration, or invasiveness.
CONCLUSIONS: NPM1 may play an important role in tumor progress in SACC and is a
potential biomarker for SACC.
PMID- 27501254
TI - How coaching can play a key role in the development of nurse managers.
AB - AIMS AND OBJECTIVES: The aim of this study was to explore empirically the role
that coaching plays in the development of nurse managers in order to inform
further research and policy makers about the potential utility and value of this
means of development. BACKGROUND: There is evidence of the importance of the role
of nurse managers who are first line managers of a team of nurses within any
health sector. However, there appears to be little understanding of the United
Kingdom wide scope of nurse manager development across the United Kingdom and the
means to increase its effectiveness. At the same time, it appears that some nurse
managers receive coaching to help in their development. DESIGN: This is a mixed
methods study, using a pragmatist paradigm. METHODS: Data was gathered from a
quantitative survey and qualitative interviews. This paper is reporting the
results of the qualitative interviews only. Twenty-one qualitative interviews
were undertaken with nurse managers, coaches and directors of nursing to draw out
their own experiences of coaching for nurse managers. Thematic analysis framework
was used for data interrogation, identifying new patterns and emerging themes.
RESULTS: Themes that emerged from interviews include how nurse managers were
introduced to coaching, how they balanced transitions, the role of reflection,
the value of relationships and overlaps between clinical supervision, mentoring
and coaching. CONCLUSIONS: Findings show that following coaching, nurse managers
gained increased resilience, confidence and better coping mechanisms. This
resulted in perceived improved team management and cohesion and appeared to lead
to better quality of care for patients. RELEVANCE TO CLINICAL PRACTICE: This
study suggests the importance of nurse managers accessing coaching, to enable
transformational leadership of their teams of nurses. It suggests also the
importance of organisations supporting a coaching culture, to ensure staff
satisfaction, motivation and improved quality of patient care.
PMID- 27501251
TI - Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.
AB - A novel family of small molecule inhibitors of voltage-gated sodium channels
(NaVs) based on the structure of batrachotoxin (BTX), a well-known channel
agonist, is described. Protein mutagenesis and electrophysiology experiments
reveal the binding site as the inner pore region of the channel, analogous to
BTX, alkaloid toxins, and local anesthetics. Homology modeling of the eukaryotic
channel based on recent crystallographic analyses of bacterial NaVs suggests a
mechanism of action for ion conduction block.
PMID- 27501255
TI - The hidden symbols of the female anatomy in Michelangelo Buonarroti's ceiling in
the Sistine Chapel.
AB - A number of published articles have suggested that each element of Renaissance
art contains an inner meaning. Some of these elements include the choice of theme
and protagonists, faces selected for the characters, colors used, species of
flowers and trees chosen, animals depicted, positions of the elements, posture of
the characters and their gestures, juxtapositions in the scenes, and even the
very scenario or landscape. All of these elements are thought to have hidden
meanings. In this context, this manuscript presents a new hypothesis suggesting
that Michelangelo Buonarroti (1475-1564) may have concealed symbols associated
with female anatomy in the ceiling of the Sistine Chapel (painted 1508-1512) in
Rome. Thus, this paper is useful to better understand the history of anatomy and
corroborates recent descriptions that have suggested the possible existence of
anatomic figures concealed in many of Michelangelo's works. Clin. Anat. 29:911
916, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27501256
TI - Trivariate mover-stayer counting process models for investigating joint damage in
psoriatic arthritis.
AB - In psoriatic arthritis, many patients do not develop permanent joint damage even
after a prolonged follow-up. This has led several authors to consider the
possibility of a subpopulation of stayers (those who do not have the propensity
to experience the event of interest), as opposed to assuming the entire
population consist of movers (those who have the propensity to experience the
event of interest). In addition, it is recognised that the damaged joints process
may act very differently across different joint areas, particularly the hands,
feet and large joints. From a clinical perspective, interest lies in identifying
possible relationships between the damaged joints processes in these joint areas
for the movers and estimating the proportion of stayers in these joint areas, if
they exist. For this purpose, this paper proposes a novel trivariate mover-stayer
model consisting of mover-stayer truncated negative binomial margins, and patient
level dynamic covariates and random effects in the models for the movers and
stayers, respectively. The model is then extended to have a two-level mover
stayer structure for its margins so that the nature of the stayer property can be
investigated. A particularly attractive feature of the proposed models is that
only an optimisation routine is required in their model fitting procedures. (c)
2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
PMID- 27501257
TI - Acquired palatal groove and delayed oral feeding in preterm infants.
AB - BACKGROUND: Acquired palatal groove has been reported in the 1970s and 1980s, but
its current incidence in Japanese newborns is unclear. The aims of this study
were to determine the incidence of palatal groove in preterm infants and to
evaluate whether this condition affects oral feeding ability. METHODS: We
conducted a prospective observational study among very low-birthweight infants
born at Takatsuki General Hospital, Osaka, between March and October in 2010. The
shape of the hard palate was classified into three types: normal, narrow high
arched palate, and palatal groove. RESULTS: Among the 37 enrolled infants, 14
(38%) had palatal groove. In particular, among the 29 infants with birthweight
<1000 g, palatal groove was observed in 48% of these patients, and only 10% were
normal. Infants with palatal groove were ventilated for considerably more days
with oral endotracheal tube than those without palate groove, even after
adjustment for gestational age, birthweight, and duration of oral duodenal tube
placement (OR, 1.11). Establishment of oral feeding and disappearance of choking
on milk were considerably delayed in infants with palatal groove. Transient oral
feeding difficulty requiring thickened-feed intervention was observed only in
infants with palatal groove; on multi-regression analysis this difficulty seemed
to be induced by the palatal groove. CONCLUSIONS: Palatal groove formation
induced by oral endotracheal intubation occurs with a high frequency in preterm
infants, and this is likely to affect oral feeding ability.
PMID- 27501259
TI - Viruses and the Diversity of Cell Death.
AB - Cell death is a common outcome of virus infection. In some cases, cell death
curbs virus replication. In others, cell death enhances virus dissemination and
contributes to tissue injury, exacerbating viral disease. Three forms of cell
death are observed following virus infection-apoptosis, necroptosis, and
pyroptosis. In this review, I describe the core machinery needed for each of
these forms of cell death. Using representative viruses, I highlight how distinct
stages of virus replication initiate signaling pathways that elicit these forms
of cell death. I also discuss viral strategies to overcome the deleterious
effects of cell death on virus propagation and the consequences of cell death for
host physiology.
PMID- 27501260
TI - Integrins as Herpesvirus Receptors and Mediators of the Host Signalosome.
AB - The repertoire of herpesvirus receptors consists of nonintegrin and integrin
molecules. Integrins interact with the conserved glycoproteins gH/gL or gB. This
interaction is a conserved biology across the Herpesviridae family, likely
directed to promote virus entry and endocytosis. Herpesviruses exploit this
interaction to execute a range of critical functions that include (a) relocation
of nonintegrin receptors (e.g., herpes simplex virus nectin1 and Kaposi's sarcoma
associated herpesvirus EphA2), or association with nonintegrin receptors (i.e.,
human cytomegalovirus EGFR), to dictate species-specific entry pathways; (b)
activation of multiple signaling pathways (e.g., Ca2+ release, c-Src, FAK, MAPK,
and PI3K); and (c) association with Rho GTPases, tyrosine kinase receptors, Toll
like receptors, which result in cytoskeletal remodeling, differential cell type
targeting, and innate responses. In turn, integrins can be modulated by viral
proteins (e.g., Epstein-Barr virus LMPs) to favor spread of transformed cells. We
propose that herpesviruses evolved a multipartite entry system to allow
interaction with multiple receptors, including integrins, required for their
sophisticated life cycle.
PMID- 27501258
TI - Human Cytomegalovirus Latency: Approaching the Gordian Knot.
AB - Herpesviruses have evolved exquisite virus-host interactions that co-opt or evade
a number of host pathways to enable the viruses to persist. Persistence of human
cytomegalovirus (CMV), the prototypical betaherpesvirus, is particularly complex
in the host organism. Depending on host physiology and the cell types infected,
CMV persistence comprises latent, chronic, and productive states that may occur
concurrently. Viral latency is a central strategy by which herpesviruses ensure
their lifelong persistence. Although much remains to be defined about the virus
host interactions important to CMV latency, it is clear that checkpoints composed
of viral and cellular factors exist to either maintain a latent state or initiate
productive replication in response to host cues. CMV offers a rich platform for
defining the virus-host interactions and understanding the host biology important
to viral latency. This review describes current understanding of the virus-host
interactions that contribute to viral latency and reactivation.
PMID- 27501262
TI - A Cap-to-Tail Guide to mRNA Translation Strategies in Virus-Infected Cells.
AB - Although viruses require cellular functions to replicate, their absolute
dependence upon the host translation machinery to produce polypeptides
indispensable for their reproduction is most conspicuous. Despite their
incredible diversity, the mRNAs produced by all viruses must engage cellular
ribosomes. This has proven to be anything but a passive process and has revealed
a remarkable array of tactics for rapidly subverting control over and dominating
cellular regulatory pathways that influence translation initiation, elongation,
and termination. Besides enforcing viral mRNA translation, these processes
profoundly impact host cell-intrinsic immune defenses at the ready to deny
foreign mRNA access to ribosomes and block protein synthesis. Finally, genome
size constraints have driven the evolution of resourceful strategies for
maximizing viral coding capacity. Here, we review the amazing strategies that
work to regulate translation in virus-infected cells, highlighting both virus
specific tactics and the tremendous insight they provide into fundamental
translational control mechanisms in health and disease.
PMID- 27501261
TI - Properties and Functions of the Dengue Virus Capsid Protein.
AB - Dengue virus affects hundreds of millions of people each year around the world,
causing a tremendous social and economic impact on affected countries. The aim of
this review is to summarize our current knowledge of the functions, structure,
and interactions of the viral capsid protein. The primary role of capsid is to
package the viral genome. There are two processes linked to this function: the
recruitment of the viral RNA during assembly and the release of the genome during
infection. Although particle assembly takes place on endoplasmic reticulum
membranes, capsid localizes in nucleoli and lipid droplets. Why capsid
accumulates in these locations during infection remains unknown. In this review,
we describe available data and discuss new ideas on dengue virus capsid functions
and interactions. We believe that a deeper understanding of how the capsid
protein works during infection will create opportunities for novel antiviral
strategies, which are urgently needed to control dengue virus infections.
PMID- 27501263
TI - Polyomavirus Persistence.
AB - Mammalian polyomaviruses are characterized by establishing persistent infections
in healthy hosts and generally causing clinical disease only in hosts whose
immune systems are compromised. Despite the fact that these viruses were
discovered decades ago, our knowledge of the mechanisms that govern viral
persistence and reactivation is limited. Whereas mouse polyomavirus has been
studied in a fair amount of detail, our understanding of the human viruses in
particular is mostly inferred from experiments aimed at addressing other
questions. In this review, we summarize the state of our current knowledge, draw
conclusions when possible, and suggest areas that are in need of further study.
PMID- 27501266
TI - Bioactive gold(i) complexes with 4-mercaptoproline derivatives.
AB - Unprecedented gold(i) bioconjugates bearing non-proteinogenic amino acid 4
mercaptoproline species as bioorganic ligands have been prepared. Firstly, the
synthesis of Boc-Pro(SH)-OMe (1) has been accomplished by standard procedures.
The subsequent reaction of 1 with [AuCl(PR3)] gives complexes Boc-Pro(SAuPR3)-OMe
(PR3 = PPh3 (2), PPh2Py (3)). Starting from complex 2 several structural
modifications have been performed, in addition to the incorporation of a
different phosphine in 3, such as the formation of the acid Boc-Pro(SAuPPh3)-OH
(4), the synthesis of a dipeptide derivative by coupling the amino acid glycine
tert-butyl ester Boc-Pro(SAuPPh3)-Gly-O(t)Bu (5), or the coordination of another
gold phosphine fragment to the sulfur atom as in [Boc-Pro(SAuPPh3)2-OMe]OTf (6).
The cytotoxic activity in vitro of these complexes has been evaluated against
three different tumor human cell lines, A549 (lung carcinoma), Jurkat (T-cell
leukaemia) and MiaPaca2 (pancreatic carcinoma). All the complexes displayed
excellent cytotoxic activity with IC50 values in the low MUM range and even in
the nM range in some cases. Structure-Activity Relationships (SAR) observed from
this family of complexes opens the possibility of designing more potent and
selective promising gold(i) anticancer agents.
PMID- 27501265
TI - Determination of Biofilm Initiation on Virus-infected Cells by Bacteria and
Fungi.
AB - The study of polymicrobial interactions across the taxonomic kingdoms that
include fungi, bacteria and virus have not been previously examined with respect
to how viral members of the microbiome affect subsequent microbe interactions
with these virus-infected host cells. The co-habitation of virus with bacteria
and fungi is principally present on the mucosal surfaces of the oral cavity and
genital tract. Mucosal cells, particularly those with persistent chronic or
persistent latent viral infections, could have a significant impact on members of
the microbiome through virus alteration in number and type of receptors
expressed. Modification in host cell membrane architecture would result in
altered ability of subsequent members of the normal flora and opportunistic
pathogens to initiate the first step in biofilm formation, i.e., adherence. This
study describes a method for quantitation and visual examination of HSV's effect
on the initiation of biofilm formation (adherence) of S. aureus and C. albicans.
PMID- 27501264
TI - Genomic Analysis of Viral Outbreaks.
AB - Genomic analysis is a powerful tool for understanding viral disease outbreaks.
Sequencing of viral samples is now easier and cheaper than ever before and can
supplement epidemiological methods by providing nucleotide-level resolution of
outbreak-causing pathogens. In this review, we describe methods used to answer
crucial questions about outbreaks, such as how they began and how a disease is
transmitted. More specifically, we explain current techniques for viral
sequencing, phylogenetic analysis, transmission reconstruction, and evolutionary
investigation of viral pathogens. By detailing the ways in which genomic data can
help us understand viral disease outbreaks, we aim to provide a resource that
will facilitate the response to future outbreaks.
PMID- 27501267
TI - The effect of rumen ciliates on chitinolytic activity, chitin content and the
number of fungal zoospores in the rumen fluid of sheep.
AB - The objective of this study was to investigate the effect of selected protozoa on
the degradation and concentration of chitin and the numbers of fungal zoospores
in the rumen fluid of sheep. Three adult ewes were fed a hay-concentrate diet,
defaunated, then monofaunated with Entodinium caudatum or Diploplastron affine
alone and refaunated with natural rumen fauna. The average density of the
protozoa population varied from 6.1 . 10(4) (D. affine) to 42.2 . 10(4) cells/ml
rumen fluid (natural rumen fauna). The inoculation of protozoa in the rumen of
defaunated sheep increased the total activity of chitinolytic enzymes from 2.9 to
3.6 MUmol N-acetylglucosamine/g dry matter (DM) of rumen fluid per min, the
chitin concentration from 6.3 to 7.2 mg/g DM of rumen fluid and the number of
fungal zoospores from 8.1 to 10.9 . 10(5) cells/ml rumen fluid. All examined
indices showed diurnal variations. Ciliate population density was highest
immediately prior to feeding and lowest at 4 h thereafter. The opposite effects
were observed for the numbers of fungal zoospores, the chitin concentration and
chitinolytic activity. Furthermore, it was found that chitin from zoospores may
account for up to 95% of total microbial chitin in the rumen fluid of sheep. In
summary, the examined ciliate species showed the ability of chitin degradation as
well as a positive influence on the development of the ruminal fungal population.
PMID- 27501268
TI - Temporal increase in thymocyte negative selection parallels enhanced thymic
SIRPalpha+ DC function.
AB - Dysregulation of negative selection contributes to T-cell-mediated autoimmunity,
such as type 1 diabetes. The events regulating thymic negative selection,
however, are ill defined. Work by our group and others suggest that negative
selection is inefficient early in ontogeny and increases with age. This study
examines temporal changes in negative selection and the thymic DC compartment.
Peptide-induced thymocyte deletion in vivo was reduced in newborn versus 4-week
old NOD mice, despite a similar sensitivity of the respective thymocytes to
apoptosis induction. The temporal increase in negative selection corresponded
with an elevated capacity of thymic antigen-presenting cells to stimulate T
cells, along with altered subset composition and function of resident DC. The
frequency of signal regulatory protein alpha+ (SIRPalpha+ ) and plasmacytoid DCs
was increased concomitant with a decrease in CD8alpha+ DC in 4-week-old NOD
thymi. Importantly, 4-week-old versus newborn thymic SIRPalpha+ DC exhibited
increased antigen processing and presentation via the MHC class II but not class
I pathway, coupled with an enhanced T-cell stimulatory capacity not seen in
thymic plasmacytoid DC and CD8alpha+ DC. These findings indicate that the
efficiency of thymic DC-mediated negative selection is limited early after birth,
and increases with age paralleling expansion of functionally superior thymic
SIRPalpha+ DC.
PMID- 27501269
TI - Psychosocial Well-being of Siblings of Adolescents with Anorexia Nervosa.
AB - OBJECTIVE: Anorexia nervosa (AN) is often first diagnosed in the adolescent
years. The treatment with the greatest evidence during this time is family-based
treatment (FBT). In FBT, siblings are expected to attend treatment sessions;
however, sibling well-being during this time has not been well researched. This
study aimed to explore sibling well-being when the ill child was initially
diagnosed with AN and after FBT had been completed. METHOD: Eighty-five parents
and 55 siblings of adolescents with AN completed the Strengths and Difficulties
Questionnaire at diagnosis. In addition, 88 parents and 46 siblings completed the
Strengths and Difficulties Questionnaire after finishing treatment. RESULTS:
Mothers and fathers reported siblings to have lower levels of conduct problems in
comparison with population norms. Mothers also reported lower levels of prosocial
behaviours. Siblings reported higher levels of emotional difficulties and
hyperactivity in comparison with their peers. There were no differences in
reported psychosocial well-being of siblings between diagnosis and following FBT.
CONCLUSIONS: Siblings of adolescents with AN have poorer psychosocial adjustment
than their peers, both before and after FBT. Clinicians and parents are
encouraged to be aware of sibling difficulties and seek additional support if
required. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders
Association.
PMID- 27501270
TI - Palliative care for patients with hematological malignancies: Time for a new
model.
PMID- 27501271
TI - CML patients show sperm alterations at diagnosis that are not improved with
imatinib treatment.
PMID- 27501272
TI - Similarity in G matrix structure among natural populations of Arabidopsis lyrata.
AB - Understanding the stability of the G matrix in natural populations is fundamental
for predicting evolutionary trajectories; yet, the extent of its spatial
variation and how this impacts responses to selection remain open questions. With
a nested paternal half-sib crossing design and plants grown in a field
experiment, we examined differences in the genetic architecture of flowering
time, floral display, and plant size among four Scandinavian populations of
Arabidopsis lyrata. Using a multivariate Bayesian framework, we compared the
size, shape, and orientation of G matrices and assessed their potential to
facilitate or constrain trait evolution. Flowering time, floral display and
rosette size varied among populations and significant additive genetic variation
within populations indicated potential to evolve in response to selection. Yet,
some characters, including flowering start and number of flowers, may not evolve
independently because of genetic correlations. Using a multivariate framework, we
found few differences in the genetic architecture of traits among populations. G
matrices varied mostly in size rather than shape or orientation. Differences in
multivariate responses to selection predicted from differences in G were small,
suggesting overall matrix similarity and shared constraints to trait evolution
among populations.
PMID- 27501273
TI - Preparation and Antiproliferative Activity of Liposomes Containing a Combination
of Cisplatin and Procainamide Hydrochloride.
AB - We have previously reported the enhancement of the antiproliferative and
apoptotic activities of cis-diamminedichloroplatinum(II) (DDP) when it is
coadministered with a class I antiarrhythmic drug procainamide hydrochloride
(PA). Here, we determined the antiproliferative activity of DDP, either in
solution or loaded in liposomes, in the presence of PA, in the bulk solution, or
directly embedded in liposomes together with DDP. Our results show that PA
potentiates the activity of DDP-liposomes and that this effect is maintained at
least in some of the investigated cell types when both drugs were mixed and
loaded together into liposomes.
PMID- 27501274
TI - Engineering a Prototypic P-type ATPase Listeria monocytogenes Ca(2+)-ATPase 1 for
Single-Molecule FRET Studies.
AB - Approximately 30% of the ATP generated in the living cell is utilized by P-type
ATPase primary active transporters to generate and maintain electrochemical
gradients across biological membranes. P-type ATPases undergo large
conformational changes during their functional cycle to couple ATP hydrolysis in
the cytoplasmic domains to ion transport across the membrane. The Ca(2+)-ATPase
from Listeria monocytogenes, LMCA1, was found to be a suitable model of P-type
ATPases and was engineered to facilitate single-molecule FRET studies of
transport-related structural changes. Mutational analyses of the endogenous
cysteine residues in LMCA1 were performed to reduce background labeling without
compromising activity. Pairs of cysteines were introduced into the optimized low
reactivity background, and labeled with maleimide derivatives of Cy3 and Cy5
resulting in site-specifically double-labeled protein with moderate activity.
Ensemble and confocal single-molecule FRET studies revealed changes in FRET
distribution related to structural changes during the transport cycle, consistent
with those observed by X-ray crystallography for the sarco/endoplasmic reticulum
Ca(2+) ATPase (SERCA). Notably, the cytosolic headpiece of LMCA1 was found to be
distinctly more compact in the E1 state than in the E2 state. Thus, the
established experimental system should allow future real-time FRET studies of the
structural dynamics of LMCA1 as a representative P-type ATPase.
PMID- 27501275
TI - Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential
Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss.
AB - Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of
kidney loss. Among DSA characteristics, graft homing has been suggested as an
indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA)
graft homing on kidney transplantation outcome. Graft biopsy specimens and
parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed.
Serum samples and eluates from graft biopsy specimens were tested for the
presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were
never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of
sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher
homing capability was expressed by class II sDSAs endowed with high mean
fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with
available sequential biopsy specimens, we detected gDSAs before the appearance of
antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not
allow stratification for antibody-mediated graft lesions and graft loss. However,
a consistent detection of skewed unique DSA specificities was observed over time
within the graft, likely responsible for the damage. Our results indicate that
gDSAs could represent an instrumental tool to identify, among sDSAs, clinically
relevant antibody specificities requiring monitoring and possibly guiding patient
management.
PMID- 27501277
TI - Challenges faced by international nurses when migrating: an integrative
literature review.
AB - AIM: Results from this literature review were used to identify the challenges
faced by international nurses in their host countries following migration.
BACKGROUND: The increasing strain of nursing shortages in the healthcare system
has led to the recruitment of international nurses among many countries. However,
following migration, international nurses are faced with challenges that may
result in poor integration with their host countries. METHODS: Using Cooper's
five stages for integrative research reviews, a literature search was conducted
across seven databases using a PRISMA search strategy. Additional manual searches
were also conducted on the end-references of the retrieved articles. The authors
then independently reviewed the selected articles using the Joanna Briggs
Institute appraisal form to extract and generate the themes for the review.
FINDINGS: Twenty-four articles were selected for the review. The themes generated
included: (i) difficulty orientating; (ii) a longing for what is missing; (iii)
professional development and devaluing; (iv) communication barriers; (v)
discrimination and marginalization; (vi) personal and professional differences;
and (vii) a meaningful support system. IMPLICATIONS FOR POLICY AND PRACTICE: By
identifying the challenges faced by international nurses, interventions that
ensure equal treatment (e.g. multifaceted transition programmes and culturally
sensitive 'buddy' systems) can be implemented to help international nurses adapt
to their new environments. Adequate communication can be achieved by encouraging
international nurses to speak English and learn the colloquial language and non
verbal behaviours used by native nurses. CONCLUSION: With good integration
international nurses may be able to reach their full career potential as
professional nurses in their host countries. The adaptation process is a dynamic
process that requires effort from both international and native nurses. Thus, any
strategies that are developed and implemented must be multifaceted.
PMID- 27501276
TI - Quantification of Neural Ethanol and Acetaldehyde Using Headspace GC-MS.
AB - BACKGROUND: There is controversy regarding the active agent responsible for
alcohol addiction. The theory that ethanol (EtOH) itself was the agent in alcohol
drinking behavior was widely accepted until acetaldehyde (AcH) was found in the
brain. The importance of AcH formation in the brain is still subject to
speculation due to the lack of a method to accurately assay the AcH levels
directly. A highly sensitive gas chromatography mass spectrometry (GC-MS) method
to reliably determine AcH concentration with certainty is needed to address
whether neural AcH is indeed responsible for increased alcohol consumption.
METHODS: A headspace gas chromatograph coupled to selected-ion monitoring MS was
utilized to develop a quantitative assay for AcH and EtOH. Our GC-MS approach was
carried out using a Bruker Scion 436-GC SQ MS. RESULTS: Our approach yields
limits of detection of AcH in the nanomolar range and limits of quantification in
the low micromolar range. Our linear calibration includes 5 concentrations with a
least-square regression greater than 0.99 for both AcH and EtOH. Tissue analyses
using this method revealed the capacity to quantify EtOH and AcH in blood, brain,
and liver tissue from mice. CONCLUSIONS: By allowing quantification of very low
concentrations, this method may be used to examine the formation of EtOH
metabolites, specifically AcH, in murine brain tissue in alcohol research.
PMID- 27501278
TI - The Dynamic Integrated Evaluation Model (DIEM): Achieving Sustainability in
Organizational Intervention through a Participatory Evaluation Approach.
AB - Recently, there have been calls to develop ways of using a participatory approach
when conducting interventions, including evaluating the process and context to
improve and adapt the intervention as it evolves over time. The need to integrate
interventions into daily organizational practices, thereby increasing the
likelihood of successful implementation and sustainable changes, has also been
highlighted. We propose an evaluation model-the Dynamic Integrated Evaluation
Model (DIEM)-that takes this into consideration. In the model, evaluation is
fitted into a co-created iterative intervention process, in which the
intervention activities can be continuously adapted based on collected data. By
explicitly integrating process and context factors, DIEM also considers the
dynamic sustainability of the intervention over time. It emphasizes the practical
value of these evaluations for organizations, as well as the importance of their
rigorousness for research purposes. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501279
TI - TRUST trial: BAY 86-6150 use in haemophilia with inhibitors and assessment for
immunogenicity.
AB - INTRODUCTION: The most serious and challenging complication of haemophilia
treatment is development of inhibitors to replacement factors VIII or IX.
Innovative therapies currently being explored for patients with haemophilia and
inhibitors include BAY 86-6150, a modified recombinant activated factor VII
(FVIIa). Immunogenicity remains a substantial barrier in this endeavour. AIM: To
present safety and efficacy results of the BAY 86-6150 study in patients with
inhibitors and report detailed analysis of epitope mapping in a patient who
developed anti-BAY 86-6150 antibodies. METHODS: Patients aged 12-62 years with
moderate or severe haemophilia A or B were eligible for the phase 3 TRUST trial
if they had a history of high-titre inhibitors. Four escalating doses of BAY 86
6150 (6.5, 20, 50, 90 MUg kg-1 ) were planned with >=10 patients per dose level.
Bleeding episodes were treated with BAY 86-6150. Development of anti-BAY 86-6150
antibodies was considered a serious adverse event. RESULTS: TRUST was
discontinued after one patient in the 6.5-MUg kg-1 cohort developed anti-BAY 86
6150 neutralizing antibodies following three exposures. The anti-BAY 86-6150
antibodies cross-reacted with and neutralized wild-type FVIIa (WT-FVIIa). Post
hoc epitope mapping using peripheral blood mononuclear cells from the responding
patient found that none of the 14 peptides unique to BAY 86-6150 were recognized
by the patient's T cells, but strong responses were detected against 2 WT-FVIIa
peptides. CONCLUSION: In the single patient with haemophilia A who developed anti
BAY 86-6150 antibodies, results of T-cell epitope mapping indicated BAY 86-6150
was no more immunogenic than WT-FVIIa.
PMID- 27501280
TI - Features and Outcome of Autonomous Thyroid Nodules in Children: 31 Consecutive
Patients Seen at a Single Center.
AB - CONTEXT: Most thyroid nodules are benign and their accurate identification can
avoid unnecessary procedures. In adult patients, documentation of nodule autonomy
is accepted as reassurance of benign histology and as justification to forgo
biopsy or thyroidectomy. In contrast, the negative predictive value of nodule
autonomy in children is uncertain. Some recent publications recommend surgical
resection as initial management, but few address the degree of TSH suppression or
the specific scintigraphic criteria used to diagnose autonomy. OBJECTIVE: The
objective of the study was to study the presenting features and cancer risk of
children with autonomous nodules. DESIGN AND SETTING: Medical records of all 31
children diagnosed with autonomous nodules at our center from 2003 to 2014 were
retrospectively reviewed. PATIENTS AND RESULTS: All children met full diagnostic
criteria for autonomous nodules, defined by both autonomous 123I uptake into the
nodule and the suppression of uptake in the normal thyroid parenchyma on
scintigraphy performed during hypothyrotropinemia. The median age of presentation
was 15 years (range 3-18 y) with a female to male ratio of 15:1. Fifty-eight
percent of patients had solitary nodules and 42% had multiple nodules. The median
size of each patient's largest autonomous nodule was 39 mm (range 18-67 mm). Most
of the children in this series (68%) had diagnostic biopsies and/or operative
pathology of their largest autonomous nodule, which showed benign cytology or
histology in all cases. CONCLUSIONS: In this pediatric series, the cancer rate
observed in biopsied or resected autonomous nodules was 0%. Whereas larger
studies are needed to confirm our findings, these results agree with earlier
reports suggesting that thyroid cancer is rare in rigorously defined autonomous
nodules and support that conservative management may be offered to selected
children who meet strict diagnostic criteria for autonomous nodules, deferring
definitive therapies until adulthood when the risks of thyroidectomy and 131I
ablation are lower.
PMID- 27501281
TI - Circulating and Adipose Levels of Adipokines Associated With Insulin Sensitivity
in Nonobese Subjects With Type 2 Diabetes.
AB - CONTEXT: The adipokines chemerin, dipeptidyl peptidase 4, and adiponectin
influence insulin sensitivity. Whether their circulating levels and adipose
secretion are altered in nonobese individuals with type 2 diabetes mellitus
(T2DM) is unknown. OBJECTIVE: The objective of this study was to investigate SC
adipose secretion and serum levels of the three adipokines in relation to T2DM
features. DESIGN: Fourteen nonobese T2DM and 13 healthy men were investigated.
Insulin sensitivity and glucose control were assessed by hyperinsulinemic
euglycemic clamp, homeostasis model assessment, and glycated hemoglobin. MAIN
OUTCOME MEASURE: Association of circulating and adipose-secreted adipokines with
fat cell volume and insulin sensitivity was measured. PARTICIPANTS: Volunteers in
an outpatient academic clinic participated. RESULTS: Although adipose secretion
was similar between the groups, serum chemerin was higher (70 +/- 10 vs 50 +/- 1
ng/ml; P = .005), adiponectin lower (4.7 +/- 1.3 vs 6.8 +/- 2.2 MUg/ml; P =
.005), and dipeptidyl peptidase 4 unaltered in T2DM. Serum adiponectin (r = 0.53;
P = .005) and chemerin (r = -0.42; P = .03) correlated with adipose secreted
levels. Secreted and circulating chemerin correlated positively with adipocyte
volume (r > 0.40; P < .05), whereas serum adiponectin correlated negatively with
this measure (r = -0.61; P = .001). Adiponectin serum half-life was decreased in
T2DM (168 +/- 24 vs 186 +/- 18 minutes; P = .029) and correlated negatively with
glycated hemoglobin (r = -0.45; P = .03) and adipocyte volume (r = -0.56; P <
.003). Serum adiponectin (r = 0.57; P = .017) and chemerin (r = -0.52; P = .03)
associated with clamp measures independently of T2DM diagnosis. CONCLUSIONS: In
nonobese men, circulating adiponectin and chemerin levels are altered in T2DM
without changes in adipose secretion. Adipocyte volume is important for
variations in serum chemerin and adiponectin and for serum clearance of
adiponectin. In T2DM, poor glucose control also plays a role for adiponectin
clearance.
PMID- 27501283
TI - Partial Loss of Function of the GHRH Receptor Leads to Mild Growth Hormone
Deficiency.
AB - OBJECTIVE: Recessive mutations in GHRHR are associated with severe isolated
growth hormone deficiency (IGHD), with a final height in untreated patients of
130 cm +/- 10 cm (-7.2 +/- 1.6 SDS; males) and 114 +/- 0.7 cm (-8.3 +/- 0.1 SDS;
females). DESIGN: We hypothesized that a consanguineous Pakistani family with
IGHD in three siblings (two males, one female) would have mutations in GH1 or
GHRHR. RESULTS: Two novel homozygous missense variants [c.11G>A (p.R4Q), c.236C>T
(p.P79L)] at conserved residues were identified in all three siblings. Both were
absent from control databases, aside from pR4Q appearing once in heterozygous
form in the Exome Aggregation Consortium Browser. The brothers were diagnosed
with GH deficiency at 9.8 and 6.0 years (height SDS: -2.24 and -1.23,
respectively), with a peak GH of 2.9 MUg/liter with low IGF-1/IGF binding protein
3. Their sister presented at 16 years with classic GH deficiency (peak GH <0.1
MUg/liter, IGF-1 <3.3 mmol/liter) and attained an untreated near-adult height of
144 cm (-3.0 SDS); the tallest untreated patient with GHRHR mutations reported.
An unrelated Pakistani female IGHD patient was also compound homozygous. All
patients had a small anterior pituitary on magnetic resonance imaging. Functional
analysis revealed a 50% reduction in maximal cAMP response to stimulation with
GHRH by the p.R4Q/p.P79L double mutant receptor, with a 100-fold increase in
EC50. CONCLUSION: We report the first coexistence of two novel compound
homozygous GHRHR variants in two unrelated pedigrees associated with a partial
loss of function. Surprisingly, the patients have a relatively mild IGHD
phenotype. Analysis revealed that the pP79L mutation is associated with the
compromise in function, with the residual partial activity explaining the mild
phenotype.
PMID- 27501282
TI - Fibroblast Growth Factor 23 and Cause-Specific Mortality in the General
Population: The Northern Manhattan Study.
AB - CONTEXT: An elevated fibroblast growth factor (FGF) 23 is an independent risk
factor for cardiovascular disease and mortality in patients with kidney disease.
The relationship between FGF23 and cause-specific mortality in the general
population is unknown. OBJECTIVE: To investigate the association of elevated
FGF23 with the risk of cause-specific mortality in a racially and ethnically
diverse urban general population. DESIGN, SETTING, PARTICIPANTS: The Northern
Manhattan Study is a population-based prospective cohort study. Residents who
were > 39 years old and had no history of stroke were enrolled between 1993 and
2001. Participants with available blood samples for baseline FGF23 testing were
included in the current study (n = 2525). MAIN OUTCOME MEASURES: Cause-specific
death events. RESULTS: A total of 1198 deaths (474 vascular, 612 nonvascular, 112
unknown cause) occurred during a median follow-up of 14 years. Compared to
participants in the lowest FGF23 quintile, those in the highest quintile had a
2.07-fold higher risk (95% confidence interval [CI], 1.45, 2.94) of vascular
death and a 1.64-fold higher risk (95% CI, 1.22, 2.20) of nonvascular death in
fully adjusted models. Higher FGF23 was independently associated with increased
risk of mortality due to cancer, but only in Hispanic participants (hazard ratio
per 1 unit increase in ln FGF23 of 1.87; 95% CI, 1.40, 2.50; P for interaction =
.01). CONCLUSIONS: Elevated FGF23 was independently associated with increased
risk of vascular and nonvascular mortality in a diverse general population and
with increased risk of cancer death specifically in Hispanic individuals.
PMID- 27501284
TI - Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal
fluid barrier: involvement of plasma membrane monoamine transporter
(PMAT/SLC29A4).
AB - The elimination of histamine, an excitatory neurotransmitter, from the brain/CSF
across the blood-brain barrier and blood-CSF barrier (BCSFB) was investigated
using Wistar rats, which were anesthetized with pentobarbital sodium. An in vivo
intracerebral microinjection study suggested that there was only partial efflux
of [3 H]histamine from the rat brain across the blood-brain barrier. The [3
H]histamine elimination clearance from the rat CSF was 3.8-fold greater than that
of a CSF bulk flow marker, and the elimination of [3 H]histamine was
significantly inhibited by the co-administration of unlabeled histamine,
suggesting the involvement of a carrier-mediated process in histamine elimination
from the CSF. The uptake study of [3 H]histamine by the isolated rat choroid
plexus revealed histamine elimination from the CSF across the BCSFB. The [3
H]histamine uptake by TR-CSFB3 cells, a model cell line for the BCSFB, exhibited
temperature-dependent and saturable kinetics, suggesting the involvement of
carrier-mediated transport of histamine at the BCSFB. In the inhibition study, [3
H]histamine uptake by TR-CSFB3 cells was significantly inhibited by substrates
and/or inhibitors of plasma membrane monoamine transporter (PMAT/SLC29A4), but
not affected by substrates of organic cation transporters. These results suggest
the elimination of histamine from the CSF via plasma membrane monoamine
transporter at the BCSFB.
PMID- 27501285
TI - Implementation of a Coherent Anti-Stokes Raman Scattering (CARS) System on a
Ti:Sapphire and OPO Laser Based Standard Laser Scanning Microscope.
AB - Laser scanning microscopes combining a femtosecond Ti:sapphire laser and an
optical parametric oscillator (OPO) to duplicate the laser line have become
available for biologists. These systems are primarily designed for multi-channel
two-photon fluorescence microscopy. However, without any modification,
complementary non-linear optical microscopy such as second-harmonic generation
(SHG) or third harmonic generation (THG) can also be performed with this set-up,
allowing label-free imaging of structured molecules or aqueous medium-lipid
interfaces. These techniques are well suited for in-vivo observation, but are
limited in chemical specificity. Chemically selective imaging can be obtained
from inherent vibration signals based on Raman scattering. Confocal Raman
microscopy provides 3D spatial resolution, but it requires high average power and
long acquisition time. To overcome these difficulties, recent advances in laser
technology have permitted the development of nonlinear optical vibrational
microscopy, in particular coherent anti-Stokes Raman scattering (CARS). CARS
microscopy has therefore emerged as a powerful tool for biological and live cell
imaging, by chemically mapping lipids (via C-H stretch vibration), water (via O-H
stretch vibrations), proteins or DNA. In this work, we describe the
implementation of the CARS technique on a standard OPO-coupled multiphoton laser
scanning microscope. It is based on the in-time synchronization of the two laser
lines by adjusting the length of one of the laser beam path. We present a step-by
step implementation of this technique on an existing multiphoton system. A basic
background in experimental optics is helpful and the presented system does not
require expensive supplementary equipment. We also illustrate CARS imaging
obtained on myelin sheaths of sciatic nerve of rodent, and we show that this
imaging can be performed simultaneously with other nonlinear optical imaging,
such as standard two-photon fluorescence technique and second-harmonic
generation.
PMID- 27501286
TI - Effects of Moderators on Physical Training Programs: A Bayesian Approach.
AB - Vetter, RE, Yu, H, and Foose, AK. Effects of moderators on physical training
programs: a Bayesian approach. J Strength Cond Res 31(7): 1868-1878, 2017
Creating an optimal physical training program is an important focus in sport and
exercise research. The purpose of this research was to examine how different
moderators (age, ability level, training weeks, training frequencies, and
intensity) impacted the physiological outcomes of specific exercise training
programs (muscular strength, speed, power, and cardiorespiratory) using the
Bayesian method. A Bayesian approach uses flexible frameworks to determine the
pattern of outcomes. This Bayesian analysis combined data generated by 34
previous studies from 1984 to 2015 to improve estimates of effects; these studies
rendered 312 cases. The analyses for age were strong in cardiorespiratory and
speed but less in power and muscular strength. Ability level was not a predictor
of outcomes in each of the 4 areas. Training weeks contributed to power and
cardiorespiratory, but not for speed, whereas for strength the effect size (ES)
increased only up to the 16th week. Training frequency was a nonsignificant
predictor of ES; most of the included studies within this analysis used only
training frequencies of 2 or 3 days. Training intensity clearly contributed to
the ES. The pattern of influence for intensity level in strength was greatest
between 55 and 80%, in power it increased at 65% and continued in a positive
linear pattern, in cardiorespiratory it increased up to 65% and then plateaued,
and for speed no inferences could be made.
PMID- 27501287
TI - Watershed Planning within a Quantitative Scenario Analysis Framework.
AB - There is a critical need for tools and methodologies capable of managing aquatic
systems within heavily impacted watersheds. Current efforts often fall short as a
result of an inability to quantify and predict complex cumulative effects of
current and future land use scenarios at relevant spatial scales. The goal of
this manuscript is to provide methods for conducting a targeted watershed
assessment that enables resource managers to produce landscape-based cumulative
effects models for use within a scenario analysis management framework. Sites are
first selected for inclusion within the watershed assessment by identifying sites
that fall along independent gradients and combinations of known stressors. Field
and laboratory techniques are then used to obtain data on the physical, chemical,
and biological effects of multiple land use activities. Multiple linear
regression analysis is then used to produce landscape-based cumulative effects
models for predicting aquatic conditions. Lastly, methods for incorporating
cumulative effects models within a scenario analysis framework for guiding
management and regulatory decisions (e.g., permitting and mitigation) within
actively developing watersheds are discussed and demonstrated for 2 sub
watersheds within the mountaintop mining region of central Appalachia. The
watershed assessment and management approach provided herein enables resource
managers to facilitate economic and development activity while protecting aquatic
resources and producing opportunity for net ecological benefits through targeted
remediation.
PMID- 27501288
TI - Buckling of a holey column.
AB - We report the results from a combined experimental and numerical investigation of
buckling in a novel variant of an elastic column under axial load. We find that
including a regular line of centred holes in the column can prevent conventional,
global, lateral buckling. Instead, the local microstructure introduced by the
holes allows the column to buckle in an entirely different, internal, mode in
which the holes are compressed in alternate directions, but the column maintains
the lateral reflection symmetry about its centreline. The internal buckling mode
can be accommodated within a smaller external space than the global one; and it
is the preferred buckling mode over an intermediate range of column lengths for
sufficiently large holes. For very short or sufficiently long columns a
modification of the classical, global, lateral buckling is dominant.
PMID- 27501289
TI - Transparent and Flexible Self-Charging Power Film and Its Application in a
Sliding Unlock System in Touchpad Technology.
AB - Portable and wearable personal electronics and smart security systems are
accelerating the development of transparent, flexible, and thin-film electronic
devices. Here, we report a transparent and flexible self-charging power film
(SCPF) that functions either as a power generator integrated with an energy
storage unit or as a self-powered information input matrix. The SCPF possesses
the capability of harvesting mechanical energy from finger motions, based on the
coupling between the contact electrification and electrostatic induction effects,
and meanwhile storing the generated energy. Under the fast finger sliding, the
film can be charged from 0 to 2.5 V within 2094 s and discharge at 1 MUA for
approximately 1630 s. Furthermore, the film is able to identify personal
characteristics during a sliding motion by recording the electric signals related
to the person's individual bioelectricity, applied pressing force, sliding speed,
and so on, which shows its potential applications in security systems in touchpad
technology.
PMID- 27501291
TI - A severe case of X-linked ichthyosis showing palmar hyperlinearity without FLG
mutations.
PMID- 27501290
TI - Sequencing postoperative radiotherapy and adjuvant chemotherapy in non-small cell
lung cancer: unanswered questions on the not evidence-based approach.
AB - This editorial comments on the study by Lee et al. which reported on the use of
postoperative radiotherapy (PORT) as first strategy after resection of stage IIIA
pN2 non-small cell lung cancer (NSCLC). After completion of PORT, 41% of patients
received postoperative chemotherapy (POCT). The five-year overall survival (OS)
was significantly higher in patients treated with PORT and POCT than in patients
treated with PORT alone. Authors concluded that PORT used as first postoperative
strategy does not compromise a benefit of POCT and its implementation should be
further studied. We discuss the pros and cons of using PORT before POCT for stage
IIIA-pN2 NSCLC. Some radiobiological data support earlier use of PORT, however,
caution should be paid to not to unnecessarily delay or omit POCT because of its
demonstrated survival benefit. Concurrent postoperative radio-chemotherapy could
be an attractive approach, but we still have very limited clinical data on its
use in this indication.
PMID- 27501292
TI - Protocol of Electrochemical Test and Characterization of Aprotic Li-O2 Battery.
AB - We demonstrate a method for electrochemical testing of an aprotic Li-O2 battery.
An aprotic Li-O2 battery is made of a Li-metal anode, an aprotic electrolyte, and
an O2-breathing cathode. The aprotic electrolyte is a solution of lithium salt
with aprotic solvent; and porous carbon is commonly used as the cathode
substrate. To improve the performance, an electrocatalyst is deposited onto the
porous carbon substrate by certain deposition methods, such as atomic layer
deposition (ALD) and wet-chemistry reaction. The as-prepared cathode materials
are characterized by scanning electron microscopy (SEM), transmission electron
microscopy (TEM), and X-ray absorption near edge structure (XANES). A Swagelok
type cell, sealed in a glass chamber filled with pure O2, is used for the
electrochemical test on a battery test system. The cells are tested under either
capacity-controlled mode or voltage controlled mode. The reaction products are
investigated by electron microscopy, X-ray diffraction (XRD), X-ray photoelectron
spectroscopy (XPS), attenuated total reflection Fourier transform infrared (ATR
FTIR) spectroscopy, and Raman spectroscopy to study the possible pathway of
oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). This
protocol demonstrates a systematic and efficient arrangement of routine tests of
the aprotic Li-O2 battery, including the electrochemical test and
characterization of battery materials.
PMID- 27501293
TI - Ibudilast for the treatment of multiple sclerosis.
AB - INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disorder of the central
nervous system (CNS) characterized by inflammatory demyelination and progressive
axonal loss. Clinically, this is manifest as relapsing and remitting neurological
symptoms and progressive accumulation of disability. Ibudilast is a nonselective
phosphodiesterase inhibitor which works by blocking the cleavage of cyclic
adenosine monophosphate (cAMP). It has been found to have anti-inflammatory and
neuroprotective properties in animal studies and in-vitro studies; it is
currently being studied in progressive MS. AREAS COVERED: This article reviews
various studies looking at ibudilast as a potential therapy for MS. It summarizes
prior and current clinical trials of ibudilast in MS as well as its pharmacology.
EXPERT OPINION: Although ibudilast has not been found to decrease the focal
inflammatory activity in relapsing MS, it was shown to have an effect on
preserving brain volume and disability progression. Ibudilast may have a role in
the treatment of progressive MS phenotypes.
PMID- 27501294
TI - Genetic Basis of Nonsyndromic Sensorineural Hearing Loss in the Sub-Saharan
African Island Population of Sao Tome and Principe: The Role of the DFNB1 Locus?
AB - Hearing loss (HL) is a common condition with both genetic and environmental
causes, and it greatly impacts global health. The prevalence of HL is reportedly
higher in developing countries such as the Sub-Saharan African island of Sao Tome
and Principe, where the deaf community is estimated to be less than 1% of the
population. We investigated the role of the DFNB1 locus (GJB2 and GJB6 genes) in
the etiology of nonsyndromic sensorineural hearing loss (NSSHL) in Sao Tome and
Principe. A sample of 316 individuals, comprising 136 NSSHL patients (92
bilateral, 44 unilateral) and 180 controls, underwent a clinical and audiological
examination. Sequencing of the GJB2 coding region and testing for the (GJB6
D13S1830) and del(GJB6-D13S1854) GJB6 deletions were performed. A total of 311
out of 316 individuals were successfully analyzed regarding the GJB2 and GJB6
genetic variations, respectively. The frequency of the GJB2 coding mutations in
patients and controls was low. Some of those coding mutations are the most
commonly found in Eurasian and Mediterranean populations and have also been
identified in Portugal. None of the GJB6 deletions was present. The presence of
certain coding variants in Sao Tome and Principe suggests a non-Sub-Saharan
genetic influx and supports the previously reported genetic influx from European
(mainly Portuguese) ancestors. In summary, DFNB1 locus does not appear to be a
major contributor to NSSHL in Sao Tome and Principe. However, the presence of
both pathogenic and likely pathogenic mutations in GJB2 suggests that GJB2
related NSSHL might still occur in this population, warranting further research
on GJB2 testing in NSSHL cases.
PMID- 27501295
TI - Can Peripheral MicroRNA Expression Data Serve as Epigenomic (Upstream) Biomarkers
of Alzheimer's Disease?
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most
common form of dementia. However, biomarkers that require testing in the brain
tissue pose a formidable practical barrier to AD diagnostic innovation. MicroRNAs
(miRNAs) are responsible for control of gene expression at the
posttranscriptional level and are essential for the function of neuronal networks
and neuronal survival. miRNA expression can impact the regulation of APP (amyloid
beta A4 precursor protein), PSEN1 (presenilin 1), PSEN2 (presenilin 2), and BACE1
(beta-secretase 1) genes in the brain that were previously implicated in AD
pathophysiology. Little is known, however, on the extent to which peripheral
tissue (e.g., whole blood) miRNA variation might offer clinical predictive value
for AD. Moreover, few studies have examined multiple peripheral miRNA expression
data at the same time. We report here, to the best of our knowledge, the first
whole-blood-based and parallel study of seven miRNAs (hsa-miR-9-5p, hsa-miR-29a
3p, hsa-miR-106a-5p, hsa-miR-106b-5p, hsa-miR-107, hsa-miR-125a-3p, and hsa-miR
125b-5p) in relation to AD susceptibility. Notably, these miRNAs are situated
"upstream" to the genes implicated in AD. We measured the whole-blood miRNA
expression by a real-time polymerase chain reaction in a large study sample (n =
281), comprising patients with AD (n = 172) and healthy controls (n = 109). A
reduction in whole-blood expression of hsa-miR-9-5p, hsa-miR-106a-5p, hsa-miR
106b-5p, and hsa-miR-107 was significantly associated with an increased risk of
AD (p < 0.05). Notably, after receiver operating characteristics curve analyses,
hsa-miR-106a-5p displayed, as a predictor variable, 93% specificity and 68%
sensitivity. On the other hand, the expression of hsa-miR-29a-3p, hsa-miR-125a
3p, and hsa-miR-125b-5p was not significantly different between patients and
controls (p > 0.05). In conclusion, these observations warrant replication in
larger samples while making a contribution to translational research, precision
medicine, and biomarker literatures, by expanding the current efforts for AD
diagnostic innovation to the realm of epigenomic pathways such as miRNA
expression variation among patients.
PMID- 27501296
TI - Deciphering Cell-to-Cell Communication in Acquisition of Cancer Traits:
Extracellular Membrane Vesicles Are Regulators of Tissue Biomechanics.
AB - Deciphering the role of cell-to-cell communication in acquisition of cancer
traits such as metastasis is one of the key challenges of integrative biology and
clinical oncology. In this context, extracellular vesicles (EVs) are important
vectors in cell-to-cell communication and serve as conduits in the transfer of
cellular constituents required for cell function and for the establishment of
cellular phenotypes. In the case of malignancy, they have been shown to support
the acquisition of common traits defined as constituting the hallmarks of cancer.
Cellular biophysics has contributed to our understanding of some of these central
traits with changes in tissue biomechanics reflective of cell state. Indeed, much
is known about stiffness of the tissue scaffold in the context of cell invasion
and migration. This article advances this knowledge frontier by showing for the
first time that EVs are mediators of tissue biomechanical properties and,
importantly, demonstrates a link between the acquisition of cancer multidrug
resistance and increased tissue stiffness of the malignant mass. The methodology
used in the study employed optical coherence elastography and atomic force
microscopy on breast cancer cell monolayers and tumor spheroids. Specifically, we
show here that the acquired changes in tissue stiffness can be attributed to the
intracellular transfer of a protein complex comprising ezrin, radixin, moesin,
CD44, and P-glycoprotein. This has important implications in facilitating mechano
transduced signaling cascades that regulate the acquisition of cancer traits,
such as invasion and metastasis. Finally, this study also introduces novel
targets and strategies for diagnostic and therapeutic innovation in oncology,
with a view to prevention of metastatic spread and personalized medicine in
cancer treatment.
PMID- 27501297
TI - A Causal Network Analysis of the Fatty Acid Metabolome in African-Americans
Reveals a Critical Role for Palmitoleate and Margarate.
AB - Fatty acids are important sources of energy and possible predictors and etiologic
factors in many common complex pathologies such as cardiovascular disease,
diabetes, and certain forms of cancers. While fatty acids are thought to covary
with each other, their underlying causal networks have not been fully elucidated.
This study reports the identification and analysis of a statistical causal
network among 15 mostly long-chain fatty acids. In an African-American population
sample and using the Genome granularity-Directed Acyclic Graph (GDAG) algorithm,
we determined directions or causal relationships in the fatty acid metabolome. A
directed causal network was constructed that revealed 29 significant edges among
the 15 nodes (p < 0.001). We report that two fatty acid metabolites, palmitoleate
and margarate, which originate from dietary intake, together influence every
other fatty acid in the network. On the other hand, despite its high
connectivity, dihomo-linoleate did not appear to play an important role over the
whole fatty acid network. These findings collectively suggest possible strategic
entry points for new treatments or preventive modalities against diseases
affected by fatty acid metabolites such as cardiovascular disease, diabetes, and
obesity. Further studies examining the embedded substructure of the fatty acid
metabolite networks in independent population samples would be timely and
warranted as we move toward novel postgenomic diagnostics and therapeutics.
PMID- 27501299
TI - Second-generation anaplastic lymphoma kinase inhibitors: revolutionary or
evolutionary?
PMID- 27501300
TI - Nanoimprint of a 3D structure on an optical fiber for light wavefront
manipulation.
AB - Integration of complex photonic structures onto optical fiber facets enables
powerful platforms with unprecedented optical functionalities. Conventional
nanofabrication technologies, however, do not permit viable integration of
complex photonic devices onto optical fibers owing to their low throughput and
high cost. In this paper we report the fabrication of a three-dimensional
structure achieved by direct nanoimprint lithography on the facet of an optical
fiber. Nanoimprint processes and tools were specifically developed to enable a
high lithographic accuracy and coaxial alignment of the optical device with
respect to the fiber core. To demonstrate the capability of this new approach, a
3D beam splitter has been designed, imprinted and optically characterized.
Scanning electron microscopy and optical measurements confirmed the good
lithographic capabilities of the proposed approach as well as the desired optical
performance of the imprinted structure. The inexpensive solution presented here
should enable advancements in areas such as integrated optics and sensing,
achieving enhanced portability and versatility of fiber optic components.
PMID- 27501301
TI - Low Night Temperature Affects the Phloem Ultrastructure of Lateral Branches and
Raffinose Family Oligosaccharide (RFO) Accumulation in RFO-Transporting Plant
Melon (Cucumismelo L.) during Fruit Expansion.
AB - Due to the importance and complexity of photo assimilate transport in raffinose
family oligosaccharide (RFO)-transporting plants such as melon, it is important
to study the features of the transport structure (phloem) particularly of the
lateral branches connecting the source leaves and the sink fruits, and its
responses to environmental challenges. Currently, it is unclear to what extents
the cold environmental temperature stress would alter the phloem ultrastructure
and RFO accumulation in RFO-transporting plants. In this study, we firstly
utilized electron microscopy to investigate the changes in the phloem
ultrastructure of lateral branches and RFO accumulation in melons after being
subjected to low night temperatures (12 degrees C and 9 degrees C). The results
demonstrated that exposure to 9 degrees C and 12 degrees C altered the
ultrastructure of the phloem, with the effect of 9 degrees C being more obvious.
The most obvious change was the appearance of plasma membrane invaginations in
99% companion cells and intermediary cells. In addition, phloem parenchyma cells
contained chloroplasts with increased amounts of starch grains, sparse cytoplasm
and reduced numbers of mitochondria. In the intermediary cells, the volume of
cytoplasm was reduced by 50%, and the central vacuole was present. Moreover, the
treatment at 9 degrees C during the night led to RFO accumulation in the vascular
bundles of the lateral branches and fruit carpopodiums. These ultrastructural
changes of the transport structure (phloem) following the treatment at 9 degrees
C represented adaptive responses of melons to low temperature stresses. Future
studies are required to examine whether these responses may affect phloem
transport.
PMID- 27501302
TI - The Critical Role of Early Dengue Surveillance and Limitations of Clinical
Reporting - Implications for Non-Endemic Countries.
AB - The increasing dengue burden and epidemic severity worldwide have highlighted the
need to improve surveillance. In non-endemic areas such as Taiwan, where
outbreaks start mostly with imported cases from Southeast Asia, a closer
examination of surveillance dynamics to detect cases early is necessary. To
evaluate problems with dengue surveillance and investigate the involvement of
different factors at various epidemic stages, we investigated 632 laboratory
confirmed indigenous dengue cases in Kaohsiung City, Taiwan during 2009-2010. The
estimated sensitivity of clinical surveillance was 82.4% (521/632). Initially,
the modified serological surveillance (targeting only the contacts of laboratory
confirmed dengue cases) identified clinically unrecognized afebrile cases in
younger patients who visited private clinics and accounted for 30.4% (35/115) of
the early-stage cases. Multivariate regression indicated that hospital/medical
center visits [Adjusted Odds Ratio (aOR): 11.6, 95% confidence interval (CI): 6.3
21.4], middle epidemic stage [aOR: 2.4 (1.2-4.7)], fever [aOR: 2.3 (2.3-12.9)],
and musculo-articular pain [aOR: 1.9 (1.05-3.3)] were significantly associated
with clinical reporting. However, cases with pruritus/rash [aOR: 0.47 (0.26
0.83)] and diarrhea [aOR: 0.47 (0.26-0.85)] were underreported. In conclusion,
multiple factors contributed to dengue surveillance problems. To prevent a large
scale epidemic and minimize severe dengue cases, there is a need for integrated
surveillance incorporating entomological, clinical, serological, and virological
surveillance systems to detect early cases, followed by immediate prevention and
control measures and continuous evaluation to ensure effectiveness. This effort
will be particularly important for an arbovirus, such as Zika virus, with a high
asymptomatic infection ratio. For dengue- non-endemic countries, we recommend
serological surveillance be implemented in areas with high Aedes mosquito indices
or many breeding sites. Syndromic surveillance, spatial analysis and monitoring
changes in epidemiological characteristics using a geographical information
system, as well as epidemic prediction models involving epidemiological,
meteorological and environmental variables will be helpful for early risk
communication to increase awareness.
PMID- 27501303
TI - Analysis of Brain Mitochondria Using Serial Block-Face Scanning Electron
Microscopy.
AB - Human brain is a high energy consuming organ that mainly relies on glucose as a
fuel source. Glucose is catabolized by brain mitochondria via glycolysis, tri
carboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathways to
produce cellular energy in the form of adenosine triphosphate (ATP). Impairment
of mitochondrial ATP production causes mitochondrial disorders, which present
clinically with prominent neurological and myopathic symptoms. Mitochondrial
defects are also present in neurodevelopmental disorders (e.g. autism spectrum
disorder) and neurodegenerative disorders (e.g. amyotrophic lateral sclerosis,
Alzheimer's and Parkinson's diseases). Thus, there is an increased interest in
the field for performing 3D analysis of mitochondrial morphology, structure and
distribution under both healthy and disease states. The brain mitochondrial
morphology is extremely diverse, with some mitochondria especially those in the
synaptic region being in the range of <200 nm diameter, which is below the
resolution limit of traditional light microscopy. Expressing a mitochondrially
targeted green fluorescent protein (GFP) in the brain significantly enhances the
organellar detection by confocal microscopy. However, it does not overcome the
constraints on the sensitivity of detection of relatively small sized
mitochondria without oversaturating the images of large sized mitochondria. While
serial transmission electron microscopy has been successfully used to
characterize mitochondria at the neuronal synapse, this technique is extremely
time-consuming especially when comparing multiple samples. The serial block-face
scanning electron microscopy (SBFSEM) technique involves an automated process of
sectioning, imaging blocks of tissue and data acquisition. Here, we provide a
protocol to perform SBFSEM of a defined region from rodent brain to rapidly
reconstruct and visualize mitochondrial morphology. This technique could also be
used to provide accurate information on mitochondrial number, volume, size and
distribution in a defined brain region. Since the obtained image resolution is
high (typically under 10 nm) any gross mitochondrial morphological defects may
also be detected.
PMID- 27501304
TI - Preoperative analgesics for additional pain relief in children and adolescents
having dental treatment.
AB - BACKGROUND: Fear of dental pain is a major barrier to treatment for children who
need dental care. The use of preoperative analgesics has the potential to reduce
postoperative discomfort and intraoperative pain. We reviewed the available
evidence to determine whether further research is warranted and to inform the
development of prescribing guidelines. This is an update of a Cochrane review
published in 2012. OBJECTIVES: To assess the effects of preoperative analgesics
for intraoperative or postoperative pain relief (or both) in children and
adolescents undergoing dental treatment without general anaesthesia or sedation.
SEARCH METHODS: We searched the following electronic databases: Cochrane Oral
Health's Trials Register (to 5 January 2016), the Cochrane Central Register of
Controlled Trials (CENTRAL) (the Cochrane Library 2015, Issue 12), MEDLINE via
OVID (1946 to 5 January 2016), EMBASE via OVID (1980 to 5 January 2016), LILACS
via BIREME (1982 to 5 January 2016) and the ISI Web of Science (1945 to 5 January
2016). We searched ClinicalTrials.gov and the World Health Organization (WHO)
International Clinical Trials Registry Platform for ongoing trials to 5 January
2016. There were no restrictions regarding language or date of publication in the
searches of the electronic databases. We handsearched several specialist journals
dating from 2000 to 2011.We checked the reference lists of all eligible trials
for additional studies. We contacted specialists in the field for any unpublished
data. SELECTION CRITERIA: Randomised controlled clinical trials of analgesics
given before dental treatment versus placebo or no analgesics in children and
adolescents up to 17 years of age. We excluded children and adolescents having
dental treatment under sedation (including nitrous oxide/oxygen) or general
anaesthesia. DATA COLLECTION AND ANALYSIS: Two review authors assessed titles and
abstracts of the articles obtained from the searches for eligibility, undertook
data extraction and assessed the risk of bias in the included studies. We
assessed the quality of the evidence using GRADE criteria. MAIN RESULTS: We
included five trials in the review, with 190 participants in total. We did not
identify any new studies for inclusion from the updated search in January
2016.Three trials were related to dental treatment, i.e. restorative and
extraction treatments; two trials related to orthodontic treatment. We did not
judge any of the included trials to be at low risk of bias.Three of the included
trials compared paracetamol with placebo, only two of which provided data for
analysis (presence or absence of parent-reported postoperative pain behaviour).
Meta-analysis of the two trials gave arisk ratio (RR) for postoperative pain of
0.81 (95% confidence interval (CI) 0.53 to 1.22; two trials, 100 participants; P
= 0.31), which showed no evidence of a benefit in taking paracetamol
preoperatively (52% reporting pain in the placebo group versus 42% in the
paracetamol group). One of these trials was at unclear risk of bias, and the
other was at high risk. The quality of the evidence is low. One study did not
have any adverse events; the other two trials did not mention adverse events.Four
of the included trials compared ibuprofen with placebo. Three of these trials
provided useable data. One trial reported no statistical difference in
postoperative pain experienced by the ibuprofen group and the control group for
children undergoing dental treatment. We pooled the data from the other two
trials, which included participants who were having orthodontic separator
replacement without a general anaesthetic, to determine the effect of
preoperative ibuprofen on the severity of postoperative pain. There was a
statistically significant mean difference in severity of postoperative pain of
13.44 (95% CI -23.01 to -3.88; two trials, 85 participants; P = 0.006) on a
visual analogue scale (0 to 100), which indicated a probable benefit for
preoperative ibuprofen before this orthodontic procedure. However, both trials
were at high risk of bias. The quality of the evidence is low. Only one of the
trials reported adverse events (one participant from the ibuprofen group and one
from the placebo group reporting a lip or cheek biting injury). AUTHORS'
CONCLUSIONS: From the available evidence, we cannot determine whether or not
preoperative analgesics are of benefit in paediatric dentistry for procedures
under local anaesthetic. There is probably a benefit in using preoperative
analgesics prior to orthodontic separator placement. The quality of the evidence
is low. Further randomised clinical trials should be completed with appropriate
sample sizes and well defined outcome measures.
PMID- 27501305
TI - New Methyloceanibacter diversity from North Sea sediments includes methanotroph
containing solely the soluble methane monooxygenase.
AB - Marine methylotrophs play a key role in the global carbon cycle by metabolizing
reduced one-carbon compounds that are found in high concentrations in marine
environments. Genome, physiology and diversity studies have been greatly
facilitated by the numerous model organisms brought into culture. However, the
availability of marine representatives remains poor. Here, we report the
isolation of four novel species from North Sea sediment enrichments closely
related to the Alphaproteobacterium Methyloceanibacter caenitepidi. Each of the
newly isolated Methyloceanibacter species exhibited a clear genome sequence
divergence which was reflected in physiological differences. Notably one strain R
67174 was capable of oxidizing methane as sole source of carbon and energy using
solely a soluble methane monooxygenase and represents the first marine
Alphaproteobacterial methanotroph brought into culture. Differences in maximum
cell density of >1.5 orders of magnitude were observed. Furthermore, three
strains were capable of producing nitrous oxide from nitrate. Together, these
findings highlight the metabolic and physiologic variability within closely
related Methyloceanibacter species and provide a new understanding of the
physiological basis of marine methylotrophy.
PMID- 27501306
TI - NONSULFATED SULFAKININ CHANGES METABOLIC PARAMETERS OF INSECT FAT BODY
MITOCHONDRIA.
AB - We investigated the effect of neuropeptide, the nonsulfated sulfakinin (SK) Zopat
SK-1 (pETSDDYGHLRFa) on the mitochondrial oxidative metabolism in the Zophobas
atratus larval fat body. Mitochondria were isolated from beetle fat bodies 2 and
24 h after hormone injection. The administration of 20 pmol of Zopat-SK-1 to
feeding larvae led to decreased mitochondrial oxidative activities in larval fat
body. Diminished activities of citrate synthase and the cytochrome pathway, that
is, nonphosphorylating and phosphorylating respiration during succinate
oxidation, were observed. However, the effect of Zopat-SK-1 was more pronounced
in fat body of insects after 24 h since hormone application. In hormone-treated
larval fat bodies, mitochondrial respiration was decreased at the level of
respiratory chain and the TCA cycle as well as at the level of mitochondrial
biogenesis, as indicated by decreased activities of mitochondrial marker enzymes
in fat body homogenates. The inhibition of succinate oxidation may indicate the
role of Zopat-SK-1 in the regulation of mitochondrial complex II activity.
Moreover, decreased respiratory chain activity was accompanied by the reduced
activity of mitochondrial energy-dissipating pathway, uncoupling protein 4. The
observed decrease in mitochondrial oxidative metabolism may reflect the Zopat-SK
1-induced reduction in the metabolic rate of larval fat body linked to actual
energetic demands of animal.
PMID- 27501307
TI - Mass-Dependent and -Independent Fractionation of Mercury Isotope during Gas-Phase
Oxidation of Elemental Mercury Vapor by Atomic Cl and Br.
AB - This study presents the first measurement of Hg stable isotope fractionation
during gas-phase oxidation of Hg(0) vapor by halogen atoms (Cl(*), Br(*)) in the
laboratory at 750 +/- 1 Torr and 298 +/- 3 K. Using a relative rate technique,
the rate coefficients for Hg(0)+Cl(*) and Hg(0)+Br(*) reactions are determined to
be (1.8 +/- 0.5) * 10(-11) and (1.6 +/- 0.8) * 10(-12) cm(3) molecule(-1) s(-1),
respectively. Results show that heavier isotopes are preferentially enriched in
the remaining Hg(0) during Cl(*) initiated oxidation, whereas being enriched in
the product during oxidation by Br(*). The fractionation factors for
(202)Hg/(198)Hg during the Cl(*) and Br(*) initiated oxidations are
alpha(202/198) = 0.99941 +/- 0.00006 (2sigma) and 1.00074 +/- 0.00014 (2sigma),
respectively. A Delta(199)Hg/Delta(201)Hg ratio of 1.64 +/- 0.30 (2sigma) during
oxidation of Hg(0) by Br atoms suggests that Hg-MIF is introduced by the nuclear
volume effect (NVE). In contrast, the Hg(0) + Cl(*) reaction produces a
Delta(199)Hg/Delta(201)Hg-slope of 1.89 +/- 0.18 (2sigma), which in addition to a
high degree of odd-mass-number isotope MIF suggests impacts from MIF effects
other than NVE. This reaction also exhibits significant MIF of (200)Hg
(Delta(200)Hg, up to -0.170/00 in the reactant) and is the first physicochemical
process identified to trigger (200)Hg anomalies that are frequently detected in
atmospheric samples.
PMID- 27501308
TI - Mitochondrial genome erosion and the evolution of sex.
PMID- 27501309
TI - Specific and sustainable bioelectro-reduction of carbon dioxide to formate on a
novel enzymatic cathode.
AB - To specifically convert waste CO2 into renewable chemicals, enzymatic
electrosynthesis (EES) of formate from CO2 reduction was investigated in a
bioelectrochemical system (BES). A novel cathode with immobilized enzyme and
electropolymerized mediator-regenerator was fabricated for such
bioelectrocatalytic EES. Formate dehydrogenase from Candida boidinii (CbFDH) was
set as a new model enzyme in BES. Modified Nafion micelles with appropriate pore
size were found to be suitable for immobilization of CbFDH and protection of its
enzymatic activity and lifetime at optimal pH of 6.0. The enzymatic
electrosynthesis activity of immobilized CbFDH was characterized systematically.
Quite a small overpotential was required in the bioelectrochemical EES reaction.
A two-electron transfer process was confirmed in the CbFDH-catalyzed reduction of
bicarbonate to formate. With electro-polymerized neutral red (PolyNR) as a NADH
(mediator)-regenerator, efficient formate production could be achieved at a
maximum rate of 159.89 mg L(-1) h(-1) under poised potential of -0.80 V (vs.
SHE). The immobilized CbFDH and electropolymerized PolyNR on an enzymatic cathode
contributed greatly to sustainable EES, giving energy-rich formate as the only
catalysis product.
PMID- 27501310
TI - Effects of Ni/Fe bimetallic nanoparticles on phytotoxicity and translocation of
polybrominated diphenyl ethers in contaminated soil.
AB - In vivo studies of the interactions of polybrominated diphenyl ethers (PBDEs) in
plants have generally focused on uptake, translocation, metabolism and
accumulation, but there were limited reports about the phytotoxicity and
translocation of PBDEs in contaminated soil with the effects of nanoparticles. In
this study, the effects of Ni/Fe bimetallic nanoparticles on translocation of
polybrominated diphenyl ethers (PBDEs) in contaminated soil and its phytotoxicity
to Chinese cabbage were investigated by soil culture experiments. The results
showed that the plant biomass, germination rate, and shoot and root lengths of
treated soil (S-5) increased by 0.0044 g, 15%, and 5 and 6 mm, respectively,
compared with untreated soil (S-2B). The average Ni and Fe contents of the edible
parts(stem and leaf) of the S-5 sample, which contained 0.03 g/g Ni/Fe and 10
mg/kg BDE209, were measured at 1.71 and 184 mg/kg, respectively. The superoxide
dismutase, peroxidase and catalase activities in the S-5 sample decreased by 12%,
6.1% and 5.9%, respectively, while compared with the S-2B sample. In all
treatments, the contents of BDE209 and the total PBDEs in sample S-5 were lowest,
suggesting that the fresh Ni/Fe nanoparticles had higher toxicity than that of
the aged nanoparticles. And the lower brominated PBDEs (tri-to nona-) were
detected in samples, indicating uptake, debromination and/or metabolism of PBDEs
existed in plants. The phytotoxicity and translocation of BDE209 in the
contaminated soil decreased as a result of the effects of the Ni/Fe bimetallic
nanoparticles.
PMID- 27501311
TI - Herbicides interfere with antigrazer defenses in Scenedesmus obliquus.
AB - The extensive application of herbicides has led to a serious threat of herbicide
contamination to aquatic ecosystem. Herbicide exposure affects aquatic
communities not only by exerting toxicity on single species but also by changing
interspecific interactions. This study investigated the antigrazer defenses of
the common green alga Scenedesmus obliquus against different herbicides
[glyphosate, 2,4-dichlorophenoxyacetic acid (2,4-D), and atrazine] at various
concentrations (0-2.0 mg L(-1)). In the presence of grazer (Daphnia)-derived
cues, S. obliquus populations without herbicides formed high proportions of
multicelled (e.g., four- and eight-celled) colonies. This result confirms that S.
obliquus exhibits a morphological defense against grazing risk. At the low
concentration range of 0.002-0.02 mg L(-1), the three herbicides exerted no
influence on the growth and photosynthetic efficiency of S. obliquus, and
multicelled colonies showed constant proportions. At the high concentration range
of 0.20-2.0 mg L(-1), atrazine significantly inhibited the algal growth and
photosynthesis whereas glyphosate or 2,4-D did not. Nonetheless, these levels of
glyphosate or 2,4-D remarkably decreased the proportion of multicelled colonies,
with reduced numbers of cells per particle in Daphnia filtrate-treated
population. No eight-celled colony was formed after treatment with atrazine at
0.20-2.0 mg L(-1) despite the addition of Daphnia filtrate. These results suggest
that herbicide exposure impairs antigrazer colonial morphs in phytoplankton
although it is not sufficient to hamper algal growth. This phenomenon can
increase the risk of predation by herbivores, thereby disrupting the inducible
phytoplankton community. Furthermore, the predator-prey interactions between
herbivores and phytoplankton can be potentially changed more seriously than
previously considered.
PMID- 27501312
TI - Pesticide residues in drinking water and associated risk to consumers in
Ethiopia.
AB - Access to safe and reliable drinking water is vital for a healthy population.
However, surface water may be contaminated with pesticides because of the nearby
agricultural areas as well as from household application. Water samples were
collected from water sources in Jimma zone and Addis Ababa, Ethiopia. The
extraction and clean up of the samples were undertaken using liquid-solid and
liquid-liquid methods. Human exposure was assessed by calculating the estimated
daily intake (EDI) of pesticides in water and compared with the acceptable daily
intake (ADI) and the acute reference dose (ARfD). The mean concentrations of 2,4
D, malathion, diazinon and fenpropimorph were 1.59-13.90 MUg/l and 0.11-138 ug/l
in Jimma and Addis Ababa water sources, respectively. The residue level of some
of the pesticides were above the European drinking water guide line values, which
is an indication of an illegal use of pesticides in the study areas. Concerning
human health risk estimation, there was no acute risk (EDI < ARfD). However,
chronic risks to human health were observed from exposure to diazinon and
fenpropimorph (EDI > ADI) for Jimma and Addis Ababa populations, respectively. A
comprehensive monitoring is required to reduce the level of pesticide residues in
the water and to minimize particularly the long term human health risks.
PMID- 27501313
TI - Biomimetic Ant-Nest Electrode Structures for High Sulfur Ratio Lithium-Sulfur
Batteries.
AB - The lithium-sulfur (Li-S) rechargeable battery has the benefit of high
gravimetric energy density and low cost. Significant research currently focuses
on increasing the sulfur loading and sulfur/inactive-materials ratio, to improve
life and capacity. Inspired by nature's ant-nest structure, this research results
in a novel Li-S electrode that is designed to meet both goals. With only three
simple manufacturing-friendly steps, which include slurry ball-milling, doctor
blade-based laminate casting, and the use of the sacrificial method with water to
dissolve away table salt, the ant-nest design has been successfully recreated in
an Li-S electrode. The efficient capabilities of the ant-nest structure are
adopted to facilitate fast ion transportation, sustain polysulfide dissolution,
and assist efficient precipitation. High cycling stability in the Li-S batteries,
for practical applications, has been achieved with up to 3 mg.cm(-2) sulfur
loading. Li-S electrodes with up to a 85% sulfur ratio have also been achieved
for the efficient design of this novel ant-nest structure.
PMID- 27501314
TI - Efficacy and Safety of Beclomethasone Dipropionate versus 5-Aminosalicylic Acid
in the Treatment of Ulcerative Colitis: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Ulcerative colitis (UC) is a chronic and remitting inflammatory
disease that is characterized by chronic idiopathic inflammation of the colon and
bloody diarrhea. Currently drug treatment is the main intervention for patients
with mild to moderate UC. Mesalazine (5-ASA) and beclomethasone dipropionate
(BDP) have been widely used for the treatment of UC and have yielded satisfactory
results. This study compared the effectiveness of 5-ASA and BDP in the treatment
of UC. METHODS: The PubMed, Medline, SinoMed, Embase, and Cochrane Librinary
databases were searched for eligible studies. Data were extracted by two of the
coauthors independently and were analyzed using RevMan statistical software,
version 5.3. Weighted mean differences (WMDs), odds ratios (ORs), and 95%
confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias
Tool was used to assess the risk of bias. RESULTS: Seven randomized controlled
trials that compared BDP with 5-ASA in treating UC were identified as eligible.
The methodological quality of the trials ranged from low to moderate. A pooled
analysis of effectiveness based on the Disease Activity Index (DAI) or other
assessment method after treatment revealed that in the treatment of UC, there are
no obvious differences between BDP and 5-ASA in inducing remission and clinical
improvement (OR = 0.76, 95% CI = 0.56-1.03, P = 0.08). The total numbers of
adverse events associated with BDP and 5-ASA treatments for UC were similar (OR =
1.21, 95% CI = 0.71-2.09, P = 0.48). The safety profiles for these two drugs are
good. According to subgroup-analysis, we found no obvious differences of clinical
efficacy between BDP and 5-ASA no matter oral or enema administration was used in
the treatment of UC. A sensitivity analysis demonstrated the stability of the
pooled results. CONCLUSION: During induction treatment of mild to moderate UC,
there is no obvious difference between the two groups with respect to remission
and clinical improvement. Given that the upper confidence limit for the OR barely
exceeds 1.0 and that the p-value is close to 0.05 for this primary efficacy
outcome as well as that the horizontal block lies to the left of the vertical
line, it indicates that the clinical efficacy of BDP may be better than 5-ASA.
However, taking into account that BDP has the risk of hypothalamic-pituitary
adrenal axis (HPA) suppression, 5-ASA has a potential advantage of safety in the
treatment of mild to moderate UC.
PMID- 27501315
TI - DNA condensation in one dimension.
AB - DNA can be programmed to assemble into a variety of shapes and patterns on the
nanoscale and can act as a template for hybrid nanostructures such as conducting
wires, protein arrays and field-effect transistors. Current DNA nanostructures
are typically in the sub-micrometre range, limited by the sequence space and
length of the assembled strands. Here we show that on a patterned biochip, DNA
chains collapse into one-dimensional (1D) fibres that are 20 nm wide and around
70 um long, each comprising approximately 35 co-aligned chains at its cross
section. Electron beam writing on a photocleavable monolayer was used to
immobilize and pattern the DNA molecules, which condense into 1D bundles in the
presence of spermidine. DNA condensation can propagate and split at junctions,
cross gaps and create domain walls between counterpropagating fronts. This system
is inherently adept at solving probabilistic problems and was used to find the
possible paths through a maze and to evaluate stochastic switching circuits. This
technique could be used to propagate biological or ionic signals in combination
with sequence-specific DNA nanotechnology or for gene expression in cell-free DNA
compartments.
PMID- 27501316
TI - Integrated optical addressing of an ion qubit.
AB - The long coherence times and strong Coulomb interactions afforded by trapped ion
qubits have enabled realizations of the necessary primitives for quantum
information processing and the highest-fidelity quantum operations in any qubit
to date. Although light delivery to each individual ion in a system is essential
for general quantum manipulations and readout, experiments so far have employed
optical systems that are cumbersome to scale to even a few tens of qubits. Here
we demonstrate lithographically defined nanophotonic waveguide devices for light
routing and ion addressing that are fully integrated within a surface-electrode
ion trap chip. Ion qubits are addressed at multiple locations via focusing
grating couplers emitting through openings in the trap electrodes to ions trapped
50 MUm above the chip; using this light, we perform quantum coherent operations
on the optical qubit transition in individual 88Sr+ ions. The grating focuses the
beam to a diffraction-limited spot near the ion position with 2 MUm 1/e2 radius
along the trap axis, and we measure crosstalk errors between 10-2 and 4 * 10-4 at
distances 7.5-15 MUm from the beam centre. Owing to the scalability of the planar
fabrication technique employed, together with the tight focusing and stable
alignment afforded by the integration of the optics within the trap chip, this
approach presents a path to creating the optical systems required for large-scale
trapped-ion quantum information processing.
PMID- 27501317
TI - Ultrafast growth of single-crystal graphene assisted by a continuous oxygen
supply.
AB - Graphene has a range of unique physical properties and could be of use in the
development of a variety of electronic, photonic and photovoltaic devices. For
most applications, large-area high-quality graphene films are required and
chemical vapour deposition (CVD) synthesis of graphene on copper surfaces has
been of particular interest due to its simplicity and cost effectiveness.
However, the rates of growth for graphene by CVD on copper are less than 0.4 MUm
s-1, and therefore the synthesis of large, single-crystal graphene domains takes
at least a few hours. Here, we show that single-crystal graphene can be grown on
copper foils with a growth rate of 60 MUm s-1. Our high growth rate is achieved
by placing the copper foil above an oxide substrate with a gap of ~15 MUm between
them. The oxide substrate provides a continuous supply of oxygen to the surface
of the copper catalyst during the CVD growth, which significantly lowers the
energy barrier to the decomposition of the carbon feedstock and increases the
growth rate. With this approach, we are able to grow single-crystal graphene
domains with a lateral size of 0.3 mm in just 5 s.
PMID- 27501319
TI - Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1) as a Biomarker in the Mouse
Model of Experimental Autoimmune Myocarditis (EAM).
AB - Vascular cell adhesion molecule-1 (VCAM-1) is strongly upregulated in hearts of
mice with coxsackie virus-induced as well as in patients with viral infection
triggered dilated cardiomyopathy. Nevertheless, the role of its soluble form as a
biomarker in inflammatory heart diseases remains unclear. Therefore, we
investigated whether plasma levels of soluble VCAM-1 (sVCAM-1) directly
correlated with disease activity and progression of cardiac dysfunction in the
mouse model of experimental autoimmune myocarditis (EAM). EAM was induced by
immunization of BALB/c mice with heart-specific myosin-alpha heavy chain peptide
together with complete Freund's adjuvant. ELISA revealed strong expression of
cardiac VCAM-1 (cVCAM-1) throughout the course of EAM in immunized mice compared
to control animals. Furthermore, sVCAM-1 was elevated in the plasma of immunized
compared to control mice at acute and chronic stages of the disease. sVCAM-1 did
not correlate with the degree of acute cardiac inflammation analyzed by histology
or cardiac cytokine expression investigated by ELISA. Nevertheless, heart to body
weight ratio correlated significantly with sVCAM-1 at chronic stages of EAM.
Cardiac systolic dysfunction studied with positron emission tomography indicated
a weak relationship with sVCAM-1 at the chronic stage of the disease. Our data
provide evidence that plasma levels of sVCAM-1 are elevated throughout all stages
of the disease but showed no strong correlation with the severity of EAM.
PMID- 27501318
TI - Fast and Specific Assessment of the Halogenating Peroxidase Activity in Leukocyte
enriched Blood Samples.
AB - In this paper a protocol for the quick and standardized enrichment of leukocytes
from small whole blood samples is described. This procedure is based on the
hypotonic lysis of erythrocytes and can be applied to human samples as well as to
blood of non-human origin. The small initial sample volume of about 50 to 100 ul
makes this method applicable to recurrent blood sampling from small laboratory
animals. Moreover, leukocyte enrichment is achieved within minutes and with low
material efforts regarding chemicals and instrumentation, making this method
applicable in multiple laboratory environments. Standardized purification of
leukocytes is combined with a highly selective staining method to evaluate
halogenating peroxidase activity of the heme peroxidases, myeloperoxidase (MPO)
and eosinophil peroxidase (EPO), i.e., the formation of hypochlorous and
hypobromous acid (HOCl and HOBr). While MPO is strongly expressed in neutrophils,
the most abundant immune cell type in human blood as well as in monocytes, the
related enzyme EPO is exclusively expressed in eosinophils. The halogenating
activity of these enzymes is addressed by using the almost HOCl- and HOBr
specific dye aminophenyl fluorescein (APF) and the primary peroxidase substrate
hydrogen peroxide. Upon subsequent flow cytometry analysis all peroxidase
positive cells (neutrophils, monocytes, eosinophils) are distinguishable and
their halogenating peroxidase activity can be quantified. Since APF staining may
be combined with the application of cell surface markers, this protocol can be
extended to specifically address leukocyte sub-fractions. The method is
applicable to detect HOCl and HOBr production both in human and in rodent
leukocytes. Given the widely and diversely discussed immunological role of these
enzymatic products in chronic inflammatory diseases, this protocol may contribute
to a better understanding of the immunological relevance of leukocyte-derived
heme peroxidases.
PMID- 27501320
TI - Temporal Patterns in the Abundance of a Critically Endangered Marsupial Relates
to Disturbance by Roads and Agriculture.
AB - The aim of this study was to investigate how landscape disturbance associated
with roads, agriculture and forestry influenced temporal patterns in woylie
(Bettongia penicillata) abundance before, during and after periods of rapid
population change. Data were collected from an area of approximately 140,000 ha
of forest within the Upper Warren region in south-western Australia. Woylie
abundance was measured using cage trapping at 22 grid and five transect locations
with varying degrees of landscape disturbance between 1994 and 2012. We found
evidence that the distribution and abundance of woylies over time appears to be
related to the degree of fragmentation by roads and proximity to agriculture.
Sites furthest from agriculture supported a greater abundance of woylies and had
slower rates of population decline. Sites with fewer roads had a greater
abundance of woylies generally and a greater rate of increase in abundance after
the implementation of invasive predator control. The results of this study
suggest that landscape disturbance is less important at peak population
densities, but during times of environmental and population change, sites less
dissected by roads and agriculture better support woylie populations. This may be
due to the role these factors play in increasing the vulnerability of woylies to
introduced predators, population fragmentation, weed species invasion, mortality
from road collisions or a reduction in available habitat. Strategies that reduce
the impact of disturbance on woylie populations could include the rationalisation
of forest tracks and consolidation of contiguous habitat through the acquisition
of private property. Reducing the impact of disturbance in the Upper Warren
region could improve the resilience of this critically important woylie
population during future environmental change.
PMID- 27501321
TI - Immunoproteasomes and immunotherapy-a smoking gun for lung cancer?
AB - Lung cancer is the second most prevalent cancer in both women and men with some
221,200 new cases and 158,040 deaths reported in 2015. Almost 90% of these are
non-small cell lung cancer (NSCLC) and these patients have a very poor prognosis.
Recently a new treatment option for NSCLC appeared that strongly improved
treatment responses-immunotherapy. Here we review the various forms of
immunotherapy and how immune modification of proteasomes in lung cancer may
support the immune system in controlling NSCLC. These immunoproteasomes then
support recognition of NSCLC and may act as a biomarker for selecting responding
patients to immunotherapy.
PMID- 27501322
TI - High-risk neuroblastoma: challenges in management in low- and middle-income
countries.
PMID- 27501323
TI - Moving Parkinson care to the home.
AB - In many ways, the care of individuals with Parkinson disease does not meet their
needs. Despite the documented benefits of receiving care from clinicians with
Parkinson disease expertise, many patients (if not most) do not. Moreover,
current care models frequently require older individuals with impaired mobility,
cognition, and driving ability to be driven by overburdened caregivers to large,
complex urban medical centers. Moving care to the patient's home would make
Parkinson disease care more patient-centered. Demographic factors, including
aging populations, and social factors, such as the splintering of the extended
family, will increase the need for home-based care. Technological advances,
especially the ability to assess and deliver care remotely, will enable the
transition of care back to the home. However, despite its promise, this next
generation of home-based care will have to overcome barriers, including outdated
insurance models and a technological divide. Once these barriers are addressed,
home-based care will increase access to high quality care for the growing number
of individuals with Parkinson disease. (c) 2016 International Parkinson and
Movement Disorder Society.
PMID- 27501324
TI - Selection of Reference Genes for Expression Study in Pulp and Seeds of Theobroma
grandiflorum (Willd. ex Spreng.) Schum.
AB - Cupuassu (Theobroma grandiflorum [Willd. ex Spreng.] Schum) is a species of high
economic importance in Brazil with great potential at international level due to
the multiple uses of both its seeds and pulp in the industry of sweets and
cosmetics. For this reason, the cupuassu breeding program focused on the
selection of genotypes with high pulp and seed quality-selection associated with
the understanding of the mechanisms involved in fruit formation. Gene expression
is one of the most used approaches related to such understanding. In this sense,
quantitative real-time PCR (qPCR) is a powerful tool, since it rapidly and
reliably quantifies gene expression levels across different experimental
conditions. The analysis by qPCR and the correct interpretation of data depend on
signal normalization using reference genes, i.e. genes presenting a uniform
pattern of expression in the analyzed samples. Here, we selected and analyzed the
expression of five genes from cupuassu (ACP, ACT, GAPDH, MDH, TUB) to be used as
candidates for reference genes on pulp and seed of young, maturing and mature
cupuassu fruits. The evaluation of the gene expression stability was obtained
using the NormFinder, geNorm and BestKeeper programs. In general, our results
indicated that the GAPDH and MDH genes constituted the best combination as
reference genes to analyze the expression of cupuassu samples. To our knowledge,
this is the first report of reference gene definition in cupuassu, and these
results will support subsequent analysis related to gene expression studies in
cupuassu plants subjected to different biotic or abiotic conditions as well as
serve as a tool for diversity analysis based on pulp and seed quality.
PMID- 27501325
TI - Metabolic resuscitation in sepsis: a necessary step beyond the hemodynamic?
AB - Despite the advances made in monitoring and treatment of sepsis and septic shock,
many septic patients ultimately develop multiple organ dysfunction (MODS) and
die, suggesting that other players are involved in the pathophysiology of this
syndrome. Mitochondrial dysfunction occurs early in sepsis and has a central role
in MODS development. MODS severity and recovery of mitochondrial function have
been associated with survival. In recent clinical and experimental
investigations, mitochondrion-target therapy for sepsis and septic shock has been
suggested to reduce MODS severity and mortality. This intervention, which might
be named "metabolic resuscitation", would lead to improved mitochondrial activity
afforded by pharmacological and nutritional agents. Of particular interest in
this therapeutic strategy is thiamine, a water-soluble vitamin that plays an
essential role in cellular energy metabolism. Critical illness associated with
hypermetabolic states may predispose susceptible individuals to the development
of thiamine deficiency, which is not usually identified by clinicians as a source
of lactic acidosis. The protective effects of thiamine on mitochondrial function
may justify supplementation in septic patients at risk of deficiency.
Perspectives of supplementation with other micronutrients (ascorbic acid,
tocopherol, selenium and zinc) and potential metabolic resuscitators [coenzyme
Q10 (CoQ10), cytochrome oxidase (CytOx), L-carnitine, melatonin] to target sepsis
induced mitochondrial dysfunction are also emerging. Metabolic resuscitation may
probably be a safe and effective strategy in the treatment of septic shock in the
future. However, until then, preliminary investigations should be replicated in
further researches for confirmation. Better identification of groups of patients
presumed to benefit clinically by a certain intervention directed to
"mitochondrial resuscitation" are expected to increase driven by genomics and
metabolomics.
PMID- 27501326
TI - The presence of respiratory disorders in individuals with low back pain: A
systematic review.
AB - BACKGROUND: Inspiratory muscles, such as the diaphragm, play a key role in both
respiration and spinal control. Therefore, diaphragm dysfunctions are often
related to low back pain (LBP). However, few is known on the association between
the presence of LBP and the presence of respiratory disorders (RD). OBJECTIVES:
To perform a systematic review on the relation between RD and LBP. STUDY DESIGN:
Systematic review. METHODS: Two reviewers searched on PubMed/MEDLINE for studies
concerning LBP and RD, from 1950 up to January 2016. The search string consisted
of the following key words: low back pain, dyspnea, respiratory problems, lung
diseases, comorbidity, pulmonary disease, chronic obstructive, smoking, asthma,
allergy, sinusitis, respiratory tract infection and hyperventilation. The aim was
to evaluate a potential correlation, co-occurrence or causality between RD and
LBP. RESULTS: A total of 16 articles were included. A significant correlation
between the presence of LBP and the presence of RD such as dyspnea, asthma,
different forms of allergy, and respiratory infections was found. No correlation
was found between Chronic Obstructive Pulmonary Disease (COPD) and LBP, and no
articles were found on the correlation between hyperventilation and LBP.
CONCLUSIONS: This is the first study providing an overview of the literature on
the relation between LBP and RD. Immunological, biomechanical, psychosocial and
socio-economic factors might explain this correlation. Smoking is likely to
contribute. Future studies must reveal the causative relationship. LEVEL OF
EVIDENCE: Therapy, level 2a.
PMID- 27501327
TI - Thin-Section Computed Tomography Manifestations During Convalescence and Long
Term Follow-Up of Patients with Severe Acute Respiratory Syndrome (SARS).
AB - BACKGROUND SARS is not only an acute disease, but also leads to long-term
impaired lung diffusing capacity in some survivors. However, there is a paucity
of data regarding long-term CT findings in survivors after SARS. The aim of this
study was to assess the changes in lung function and lung thin-section computed
tomography (CT) features in patients recovering from severe acute respiratory
syndrome (SARS), especially the dynamic changes in ground-glass opacity (GGO).
MATERIAL AND METHODS Clinical and radiological data from 11 patients with SARS
were collected. The serial follow-up thin-section CTs were evaluated at 3, 6, and
84 months after SARS presentation. The distribution and predominant thin-section
CT findings of lesions were evaluated. RESULTS The extent of the lesions on the
CT scans of the 11 patients decreased at 6 and 84 months compared to 3 months.
The number of segments involved on 84-month follow-up CTs was less than those at
6 months (P<0.05). The predominant thin-section CT manifestation at 84 months
(intralobular and interlobular septal thickening) was different than that at 6
months, at which GGO was predominant. CONCLUSIONS During convalescence after
SARS, GGO and intralobular and interlobular septal thickening were the main thin
section CT manifestation. Intralobular and interlobular septal thickening
predominated over GGO at 84 months.
PMID- 27501328
TI - Graphene-Fe3 O4 as a magnetic solid-phase extraction sorbent coupled to capillary
electrophoresis for the determination of sulfonamides in milk.
AB - Graphene-Fe3 O4 nanoparticles were prepared using one-step solvothermal method
and characterized by X-ray diffraction, FTIR spectroscopy, scanning electron
microscopy, and vibrating sample magnetometry. The results demonstrated that Fe3
O4 nanoparticles were homogeneously anchored on graphene nanosheets. The as
synthesized graphene-Fe3 O4 nanoparticles were employed as sorbent for magnetic
solid-phase extraction of sulfonamides in milk prior to capillary electrophoresis
analysis. The optimal capillary electrophoresis conditions were as follows: 60
mmol/L Na2 HPO4 containing 2 mmol/L ethylenediaminetetraacetic acid disodium salt
and 24% v/v methanol as running buffer, separation voltage of 14 kV, and
detection wavelength of 270 nm. The parameters affecting extraction efficiency
including desorption solution, the amount of graphene-Fe3 O4 nanoparticles,
extraction time, and sample pH were investigated in detail. Under the optimal
conditions, good linearity (5-200 MUg/L) with correlation coefficients >=0.9910
was obtained. The limits of detection were 0.89-2.31 MUg/L. The relative standard
deviations for intraday and interday analyses were 4.9-8.5 and 4.0-9.0%,
respectively. The proposed method was successfully applied to the analysis of
sulfonamides in milk samples with recoveries ranging from 62.7 to 104.8% and
relative standard deviations less than 10.2%.
PMID- 27501329
TI - Nuclear GSK3beta promotes tumorigenesis by phosphorylating KDM1A and inducing its
deubiquitylation by USP22.
AB - Emerging evidence has shown that GSK3beta plays oncogenic roles in multiple
tumour types; however, the underlying mechanisms remain largely unknown. Here, we
show that nuclear GSK3beta is responsible for the accumulation of the histone
demethylase KDM1A and critically regulates histone H3K4 methylation during
tumorigenesis. GSK3beta phosphorylates KDM1A Ser683 upon priming phosphorylation
of KDM1A Ser687 by CK1alpha. Phosphorylation of KDM1A induces its binding with
and deubiquitylation by USP22, leading to KDM1A stabilization. GSK3beta- and
USP22-dependent KDM1A stabilization is required for the demethylation of histone
H3K4, thereby repressing BMP2, CDKN1A and GATA6 transcription, which results in
cancer stem cell self-renewal and glioblastoma tumorigenesis. In human
glioblastoma specimens, KDM1A levels are correlated with nuclear GSK3beta and
USP22 levels. Furthermore, a GSK3 inhibitor, tideglusib, sensitizes tumour
xenografts to chemotherapy in mice via KDM1A downregulation and improves
survival. Our findings demonstrate that nuclear GSK3beta- and USP22-mediated
KDM1A stabilization is essential for glioblastoma tumorigenesis.
PMID- 27501330
TI - Early polysensitization is associated with allergic multimorbidity in PARIS birth
cohort infants.
AB - BACKGROUND: Profiles of allergic sensitization are poorly documented in infancy.
Relations between early sensitization and allergic morbidity need to be
clarified. METHODS: This study dealt with children involved in the Pollution and
Asthma Risk: an Infant Study (PARIS), a population-based prospective birth
cohort. Allergic sensitization to twelve food and four inhalant allergens was
assessed at 18 months and defined by a specific immunoglobulin E (IgE) level
>=0.35 kUA /l. Health data were collected by standardized questionnaires at 2 and
6 years. Early allergic profiles were identified by an unsupervised cluster
analysis based on health data at 2 years and IgE measurements. Profiles were
compared with regard to allergic morbidity and multimorbidity at 6 years.
RESULTS: Sensitization to any allergen concerned 13.6% of infants. By cluster
analysis, 1525 infants were grouped into three profiles: 89.2% not or rarely
sensitized (only 3.7% of sensitized), 9.2% mainly sensitized to one or few
allergens (45.2% of monosensitized and 45.9% of paucisensitized) and 1.6% all
polysensitized. The prevalence of doctor-diagnosed asthma, rhinitis, eczema, food
allergy and multimorbidity at 2 years increased from profile one to profile three
(p-trend <0.001). At 6 years, symptoms of current asthma, rhinitis, eczema and
multimorbidity were significantly more frequent in the last two profiles.
CONCLUSIONS: This study highlights, as early as 18 months of age, three profiles
of increasing severity with regard to allergic sensitization and diseases. These
profiles also differ in terms of allergic morbidity at 6 years. Early
sensitization can predict allergic multimorbidity in childhood, and in the case
of early polysensitization, multimorbidity is more frequent as soon as infancy.
PMID- 27501332
TI - Psychophysical Tracking Method to Measure Taste Preferences in Children and
Adults.
AB - The Monell two-series, forced-choice, paired-comparison tracking method provides
a reliable measure of sweet taste preferences from childhood to adulthood. The
method, which is identical for children, adolescents, and adults, is of short
duration (< 15 min), does not rely on sustained attention or place demands on
memory (which would yield spurious age differences), and minimizes the impact of
language development, making this method amenable to the cognitive limitations of
pediatric populations. In this whole-mouth tasting method, subjects are asked to
taste (without swallowing) pairs of solutions of different sucrose concentrations
and to point to the solution they prefer. Each subsequent pair contains the
participant's preceding preferred concentration and an adjacent stimulus
concentration. The procedure continues until the subject chooses either a given
concentration of sucrose when paired with both a higher and a lower
concentration, or the highest or lowest concentration two consecutive times.
Subjects are prevented from reaching response criteria on the basis of first or
second position bias by the two-series design of the method, which
counterbalances the order of solution presentation within each pair between the
series (the weaker concentration is presented first in Series 1, second in Series
2). The geometric mean of the two sucrose concentrations chosen in Series 1 and 2
is an estimate of the participant's most preferred level of sucrose. Sucrose
preference as determined with this laboratory-based measure has been shown to be
associated with preference for sugars in foods and beverages and with taste
receptor genotype, family history of alcoholism, and race/ethnicity, as well as
depressive symptomatology among pediatric populations. The method has real-world
relevance and has been applied to determine most preferred level of other tastes
(e.g., salt), making it a valuable psychophysical tool.
PMID- 27501331
TI - Peperomin E reactivates silenced tumor suppressor genes in lung cancer cells by
inhibition of DNA methyltransferase.
AB - Advanced lung cancer has poor prognosis owing to its low sensitivity to current
chemotherapy agents. Therefore, discovery of new therapeutic agents is urgently
needed. In this study, we investigated the antitumor effects of peperomin E, a
secolignan isolated from Peperomia dindygulensis, a frequently used Chinese folk
medicine for lung cancer treatment. The results indicate that peperomin E has
antiproliferative effects, promoting apoptosis and cell cycle arrest in non-small
cell lung cancer (NSCLC) cell lines in a dose-dependent manner, while showing
lower toxicity against normal human lung epidermal cells. Peperomin E inhibited
tumor growth in A549 xenograft BALB/c nude mice without significant secondary
adverse effects, indicating that it may be safely used to treat NSCLC.
Furthermore, the mechanisms underlying the anticancer effects of peperomin E have
been investigated. Using an in silico target fishing method, we observed that
peperomin E directly interacts with the active domain of DNA methyltransferase 1
(DNMT1), potentially affecting its genome methylation activity. Subsequent
experiments verified that peperomin E decreased DNMT1 activity and expression,
thereby decreasing global methylation and reactivating the epigenetically
silenced tumor suppressor genes including RASSF1A, APC, RUNX3, and p16INK4, which
in turn activates their mediated pro-apoptotic and cell cycle regulatory
signaling pathways in lung cancer cells. The observations herein report for the
first time that peperomin E is a potential chemotherapeutic agent for NSCLC. The
anticancer effects of peperomin E may be partly attributable to its ability to
demethylate and reactivate methylation-silenced tumor suppressor genes through
direct inhibition of the activity and expression of DNMT1.
PMID- 27501333
TI - Preoperative navigated transcranial magnetic stimulation in patients with motor
eloquent lesions with emphasis on metastasis.
AB - Navigated transcranial magnetic stimulation (nTMS) is a frequently used, non
invasive method to map the motor cortex. It is of great value in the preoperative
workup of patients that suffer from motor eloquent brain lesions. Here, we
present a single-center experience using preoperative nTMS in cortical motor
eloquent lesions with emphasis on metastasis. All patients that underwent
preoperative nTMS between June 2013 and January 2016 were evaluated. A total of
61 patients underwent nTMS before undergoing surgery for a motor eloquent brain
lesion. Patients suffered from cerebral metastasis (23), glioblastoma (16), high
grade glioma WHO III (4), low grade glioma WHO II (4), lymphoma (2), meningioma
(8), cavernous hemangioma (3), or arteriovenous malformation (1). Thirty patients
(49.2%) presented with a preoperative motor deficit. One week after surgery,
paresis had resolved or improved in 56.7% of the patients. Out of the patients
with postoperative paresis, 89.5% experienced an improvement of motor status at
follow-up. All metastatic lesions were completely resected compared to 78.9% of
non-metastatic lesions (P = 0.02). Only 4.3% of patients with a metastatic
lesion, but 26.3% of patients with a non-metastatic lesion experienced
deterioration of motor function after surgery (P = 0.04). Preoperative nTMS is
suitable for mapping of a variety of motor eloquent brain lesions resulting in
favorable neurological outcome. Particularly in metastatic motor eloquent lesion,
motor function appears to be preserved after surgery. Clin. Anat. 29:925-931,
2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27501335
TI - Highly efficient phosphorescent materials based on Ir(iii) complexes-grafted on a
polyhedral oligomeric silsesquioxane core.
AB - A new iridium(iii) complex containing a coumarin derivative as the cyclometalated
ligand (L) and a carbazole-functionalized beta-diketonate (Cz-acac-allyl) as the
ancillary ligand, namely, Ir(iii) bis(3-(pyridin-2-yl)coumarinato-N,C(4))(1-(9
butyl-9H-carbazol-3-yl)hept-6-ene-1,3-dionato-O,O) [Ir(L)2(Cz-acac-allyl)], was
firstly synthesized as the emissive iridium(iii) complex. Then three new
phosphorescent polyhedral oligomeric silsesquioxane (POSS) materials, consisting
of the emissive Ir(iii) complex and carbazole moieties covalently attached to a
polyhedral oligomeric silsesquioxane (POSS) core were successfully synthesized by
hydrosilylation reaction in the presence of platinum(0)-1,3-divinyl-1,1,3,3
tetramethyldisiloxane (Pt-dvs) as the catalyst. These phosphorescent POSS
materials offer many advantages including amorphous properties, good thermal
stabilities, and good solubility in common solvents, and high purity via column
chromatography. The photoluminescence spectra of the POSS materials in solution
and in the solid state indicate a reduction in the degrees of interactions among
the Ir(iii) complex units and concentration quenching due to the bulky POSS core.
Solution processed light-emitting devices based on these phosphorescent POSS
materials exhibit a maximum external quantum efficiency (EQE) of 9.77%.
PMID- 27501334
TI - Endocannabinoid signaling enhances visual responses through modulation of
intracellular chloride levels in retinal ganglion cells.
AB - Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate
retina, but the role of endocannabinoids in vision is not fully understood. Here,
we identified a novel mechanism underlying a CB1R-mediated increase in retinal
ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent
inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings
revealed that inhibition of NKCC1 downstream of CB1R activation reduces
intracellular Cl(-) levels in RGCs, hyperpolarizing the resting membrane
potential. We confirmed that such hyperpolarization enhances RGC action potential
firing in response to subsequent depolarization, consistent with the increased
intrinsic excitability of RGCs observed with CB1R activation. Using a dot
avoidance assay in freely swimming Xenopus tadpoles, we demonstrate that CB1R
activation markedly improves visual contrast sensitivity under low-light
conditions. These results highlight a role for endocannabinoids in vision and
present a novel mechanism for cannabinoid modulation of neuronal activity through
Cl(-) regulation.
PMID- 27501336
TI - Nonbacterial Thrombotic Endocarditis: Pathogenesis, Diagnosis, and Management.
AB - Nonbacterial thrombotic endocarditis (NBTE), formerly known as marantic
endocarditis, is a potentially overlooked condition that involves the formation
of sterile, fibrin vegetations on heart valve leaflets. Often confused with
classic infective endocarditis during its early stages, NBTE can lead to valvular
dysfunction, heart failure, and systemic embolization when unchecked. The
pathogenesis is not entirely clear but involves a preexisting hypercoagulable
state. Diagnosis requires ruling out infection and establishing the presence of
valvular vegetations using echocardiography. Therapy for NBTE includes treating
the underlying disease, systemic anticoagulation and surgical intervention.
PMID- 27501337
TI - Standardising anaesthesia for hip fracture surgery.
PMID- 27501338
TI - Combination gemcitabine/cisplatin therapy and ERCC1 expression for resected
pancreatic adenocarcinoma: Results of a Phase II prospective trial.
AB - BACKGROUND: Standard adjuvant treatment for pancreatic adenocarcinoma (PDAC) is
gemcitabine [Gem(CONKO-001: Gem vs. placebo DFS:13.4 vs. 6.7 mo; P < 0.001;
OS:22.8 vs. 20.2 mo; P = 0.01)]. Addition of cisplatin (Cis) to Gem has resulted
in increased PFS for advanced and metastatic disease, which may be predicted by
low expression of excision repair cross-complementing group-1 (ERCC1), the key
enzyme in nucleotide excision repair. This Phase II prospective trial assesses
outcomes of patients treated with adjuvant Gem/Cis, stratifying results by tumor
ERCC1 expression. METHODS: Patients with resected PDAC were enrolled (2010-2013)
and received Gem(1,000 mg/m(2) )/Cis(50 mg/m(2) ). Tumor ERCC1 expression was
evaluated by immunohistochemistry and dichotomized into low or high expression.
Primary outcomes were recurrence-free and overall survival (RFS/OS). RESULTS: Of
22 pts, 16(73%) were Stage IIB, 5(23%) Stage IIA, and 1(4%) Stage IA. Grade 3/4
toxicity occurred in 13 pts (59%); neutropenia was most common (n = 9;41%).
Median follow-up was 37.5 months. Median RFS was 16.7 mo; OS was 35.5 mo. Low
ERCC1 (n = 15;75%) compared to high ERCC1 (n = 5;25%) was not associated with
improved RFS (12.4 vs. 16.7 mo; P = 0.68) or OS (Median not reached vs. 21.6 mo;
P = 0.22). CONCLUSIONS: Adjuvant Gem/Cis is feasible in patients with resected
pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to
historic control. Tumor ERCC1 expression can be reliably evaluated, and low
expression is present in most patients. J. Surg. Oncol. 2016;114:336-341. (c)
2016 Wiley Periodicals, Inc.
PMID- 27501339
TI - Bisphosphonate use and the risk of endometrial cancer: a meta-analysis of
observational studies.
AB - BACKGROUND: The association of bisphosphonate use and the risk of endometrial
cancer is still unclear. No meta-analysis was conducted to review the evidence
concerning this topic. METHODS: Relevant studies were identified through PubMed
and EMBASE and the Cochrane Library databases. The adjusted relative risk (RR) or
odds ratios were determined using a fixed effects or random effects model,
depending on the overall heterogeneity. RESULTS: Seven studies, including four
cohort studies and three case-control studies, met the method criteria and were
included. The random effects model showed a significant reduction in the risk
association between bisphosphonate use and endometrial cancer incidence (RR 0.75,
95%CI 0.60-0.94, p = 0.064, I2 = 49.6%). A significantly protective effect was
observed with the use of bisphosphonate for more than 1 year, and we found a
statistically significant risk reduction with the use of bisphosphonate for more
than 1 to 3 years (RR 0.58, 95%CI 0.47-0.72) and for more than 3 years (RR 0.44,
95%CI 0.28-0.70). However, with the use of bisphosphonate for less than 1 year
(RR 0.92, 95%CI 0.64-1.34), we found no protective effect against endometrial
cancer. CONCLUSIONS: We found that the use of bisphosphonate was significantly
associated with a 25% risk reduction in the incidence of endometrial cancer in
the overall analysis. Furthermore, the use of bisphosphonate for more than 1 year
but not less than 1 year may have a more beneficial effect on endometrial cancer
risk. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501340
TI - Region of Nipah virus C protein responsible for shuttling between the cytoplasm
and nucleus.
AB - Nipah virus (NiV) causes severe encephalitis in humans, with high mortality. NiV
nonstructural C protein (NiV-C) is essential for its pathogenicity, but its
functions are unclear. In this study, we focused on NiV-C trafficking in cells
and found that it localizes predominantly in the cytoplasm but partly in the
nucleus. An analysis of NiV-C mutants showed that amino acids 2, 21-24 and 110
139 of NiV-C are important for its localization in the cytoplasm. Inhibitor
treatment indicates that the nuclear export determinant is not a classical CRM1
dependent nuclear export signal. We also determined that amino acids 60-75 and 72
75 were important for nuclear localization of NiV-C. Furthermore, NiV-C mutants
that had lost their capacity for nuclear localization inhibited the interferon
(IFN) response more strongly than complete NiV-C. These results indicate that the
IFN-antagonist activity of NiV-C occurs in the cytoplasm.
PMID- 27501341
TI - Label-free fluorescent enzymatic assay of citrate synthase by CoA-Au(I) co
ordination polymer and its application in a multi-enzyme logic gate cascade.
AB - Citrate synthase (CS) is one of the key metabolic enzymes in the Krebs
tricarboxylic acid (TCA) cycle. It regulates energy generation in mitochondrial
respiration by catalysing the reaction between oxaloacetic acid (OAA) and acetyl
coenzyme A (Ac-CoA) to generate citrate and coenzyme A (CoA). CS has been shown
to be a biomarker of neurological diseases and various kinds of cancers. Here, a
label-free fluorescent assay has been developed for homogeneously detecting CS
and its inhibitor based on the in situ generation of CoA-Au(I) co-ordination
polymer (CP) and the fluorescence signal-on by SYBR Green II-stained CoA-Au(I)
CP. Because of the unique property of the CoA-Au(I) CP, this CS activity assay
method could achieve excellent selectivity and sensitivity, with a linear range
from 0.0033 U/MUL to 0.264 U/MUL and a limit of detection to be 0.00165 U/MUL.
Meanwhile, this assay method has advantages of being facile and cost effective
with quick detection. Moreover, based on this method, a biomimetic logic system
was established by rationally exploiting the cascade enzymatic interactions in
TCA cycle for chemical information processing. In the TCA cycle-derived logic
system, an AND-AND-AND-cascaded gate was rigorously operated step by step in one
pot, and is outputted by a label-free fluorescent signal with visualized readout.
PMID- 27501342
TI - Activatable molecular MRI nanoprobe for tumor cell imaging based on gadolinium
oxide and iron oxide nanoparticle.
AB - Activatable molecular MRI nanoprobe for intracellular GSH sensing was designed.
As an alternative to "always on" nanoprobe, activatable imaging nanoprobes which
are designed to amplify or boost imaging signals only in response to the targets
have attracted more and more attention. In this paper, we designed a novel
activatable molecular magnetic resonance imaging (MRI) nanoprobe for tumor cell
recognization based on a MRI signal variation induced by the distance change
between T1 and T2 contrast agents (CAs) in the presence of glutathione (GSH). To
achieve this aim, carboxyl group functionalized iron oxide nanoparticles (Fe3O4
NPs) and polyethylene glycol-coated gadolinium oxide (PEG-Gd2O3) NPs as T2 and T1
MRI CA were connected by cystamine which contains a disulfide linkage.
Transmission electron microscopic (TEM), X-ray photoelectron spectroscopy (XPS),
energy dispersive spectrometer (EDS), fourier transform infrared spectroscopy (FT
IR), mass spectra and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR)
were introduced for their characterizations. The formation of Fe3O4-cystamine
Gd2O3 (Fe3O4-SS-Gd2O3) nanocomplex resulted in a quenched T1 signal due to the
near proximity of PEG-Gd2O3 NPs to Fe3O4 NPs and a "light-up" T1 signal with the
cleavage of disulfide bond in the presence of GSH. These results provide not only
an easy way to realize MRI of tumor cells based on the overexpressed
intracellular GSH level, but also a new insight for the design of activatable MRI
nanoprobe.
PMID- 27501343
TI - Biomechanical comparison of sinus floor elevation and alternative treatment
methods for dental implant placement.
AB - OBJECTIVE: In this study, we compared the success of sinus lifting and
alternative treatment methods in applying dental implants in cases lacking
adequate bone due to pneumatization of the maxillary sinus. METHODS: In a
computer environment, 3D models were created using computerized tomography data
from a patient. Additionally, implants and abutments were scanned at the
macroscopic level, and the resulting images were transferred to the 3D models.
Five different models were examined: a control model, lateral sinus lifting
(LSL), short dental implant placement (SIP), tilted implant placement (TIP) and
distal prosthetic cantilever (DC) use. Vertical and oblique forces were applied
in each model. The compression, tension and von Mises stresses in each model were
analyzed by implementing a finite element analysis method. RESULTS: In our study,
the LSL method was observed to be the closest to the control model. The TIP model
showed high stress values under conditions of oblique forces but showed
successful results under conditions of vertical forces, and the opposite results
were observed in the SIP model. The DC model provided the least successful
results among all models. CONCLUSIONS: Based on the results of this study, the
LSL method should be the first choice among treatment options. Considering its
successful results under conditions of oblique forces, the SIP method may be
preferable to the TIP method. In contrast, every effort should be made to avoid
the use of DCs.
PMID- 27501344
TI - Older persons' experiences of what influences their vitality - a study of 65- and
75-year-olds in Finland and Sweden.
AB - Throughout the world, life expectancy has noticeably increased during the past
decade, and health promotive initiatives for older persons will therefore become
ever more important. During the past few years, interest in what constitutes the
source of health for human beings has markedly increased in health science
research. An interesting and relatively unresearched domain is what provides
older persons the strength and energy to look forward and what positively or
negatively influences older persons' vitality. The aim of the study was to
explore and describe older persons' vitality and their subjective experiences of
what influences their vitality, despite disease and suffering. The study has an
explorative and descriptive design. A comprehensive questionnaire including two
open-ended questions about vitality was sent to 4927 older persons aged 65 and
75, and a total of 2579 responded to the open-ended questions. Qualitative
content analyses were used. A safe and confirming communion, meaningful
activities, an optimal state of health and an inner strength were important
sources of vitality. Ageing that includes illness or a restricted life,
happenings in the world and in one's close environment that threaten inner
meaningfulness, and mental burdens that give rise to a feeling of hopelessness or
depression decrease vitality. Vitality is an important health resource for 65-
and 75-year-olds in that it influences a person's longing for life, love and
meaning. Accordingly, it is of fundamental importance that Registered Nurses and
other healthcare personnel strengthen older persons' vitality during the ageing
process. By taking into consideration that which positively vs. negatively
affects the vitality of each unique person, healthcare personnel can strengthen
each older person's health resources and attempt to minimise and limit what
negatively influences said person's vitality.
PMID- 27501346
TI - Discovery of a novel HLA-DRB1*09 variant, HLA-DRB1*09:28, in a Taiwanese
individual.
AB - One nucleotide substitution at residue 332 of HLA-DRB1*09:01:02 results in a
novel allele, HLA-DRB1*09:28.
PMID- 27501345
TI - Selective Enhancement of Dopamine Release in the Ventral Pallidum of
Methamphetamine-Sensitized Mice.
AB - Drugs of abuse induce sensitization, which is defined as enhanced response to
additional drug following a period of withdrawal. Sensitization occurs in both
humans and animal models of drug reinforcement and contributes substantially to
the addictive nature of drugs of abuse, because it is thought to represent
enhanced motivational wanting for drug. The ventral pallidum, a key member of the
reward pathway, contributes to behaviors associated with reward, such as
sensitization. Dopamine inputs to the ventral pallidum have not been directly
characterized. Here we provide anatomical, neurochemical, and behavioral evidence
demonstrating that dopamine terminals in the ventral pallidum contribute to
reward in mice. We report subregional differences in dopamine release, measured
by ex vivo fast-scan cyclic voltammetry: rostral ventral pallidum exhibits
increased dopamine release and uptake compared with caudal ventral pallidum,
which is correlated with tissue expression of dopaminergic proteins. We then
subjected mice to a methamphetamine-sensitization protocol to investigate the
contribution of dopaminergic projections to the region in reward related
behavior. Methamphetamine-sensitized animals displayed a 508% and 307% increase
in baseline dopamine release in the rostral and caudal ventral pallidum,
respectively. Augmented dopamine release in the rostral ventral pallidum was
significantly correlated with sensitized locomotor activity. Moreover, this
presynaptic dopaminergic plasticity occurred only in the ventral pallidum and not
in the ventral or dorsal striatum, suggesting that dopamine release in the
ventral pallidum may be integrally important to drug-induced sensitization.
PMID- 27501347
TI - Microwave-assisted cleavage of Alloc and Allyl Ester protecting groups in solid
phase peptide synthesis.
AB - Orthogonal protection of amino acid side chains in solid phase peptide synthesis
allows for selective deprotection of side chains and the formation of cyclic
peptides on resin. Cyclizations are useful as they may improve the activity of
the peptide or improve the metabolic stability of peptides in vivo. One
cyclization method often used is the formation of a lactam bridge between an
amine and a carboxylic acid. It is desirable to perform the cyclization on resin
as opposed to in solution to avoid unwanted side reactions; therefore, a common
strategy is to use -Alloc and -OAllyl protecting groups as they are compatible
with Fmoc solid phase peptide synthesis conditions. Alloc and -OAllyl may be
removed using Pd(PPh3 )4 and phenylsilane in DMF. This method can be problematic
as the reaction is most often performed at room temperature under argon gas. It
is not usually done at higher temperatures because of the fear of poisoning the
palladium catalyst. As a result, the reaction is long and reagent-intensive.
Herein, we report the development of a method in which the -Alloc/-OAllyl groups
are removed using a microwave synthesizer under atmospheric conditions. The
reaction is much faster, allowing for the removal of the protecting groups before
the catalyst is oxidized, as well as being less reagent-intensive. This method of
deprotection was tested using a variety of amino acid sequences and side chain
protecting groups, and it was found that after two 5-min deprotections at 38
degrees C, all -Alloc and -OAllyl groups were removed with >98% purity. Copyright
(c) 2016 European Peptide Society and John Wiley & Sons, Ltd.
PMID- 27501348
TI - Cobalt(II) complexes of sparfloxacin: Characterization, structure, antimicrobial
activity and interaction with DNA and albumins.
AB - The cobalt(II) complexes with the quinolone sparfloxacin (Hsf) in the absence or
presence of the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 1,10
phenanthroline (phen) or 2,2'-bipyridylamine (bipyam) were prepared and
characterized physicochemically and spectroscopically. The crystal structures of
complexes [Co(sf)2(bipy)]?3MeOH?2H2O and [Co(sf)2(phen)]?4MeOH were determined by
X-ray crystallography. The antimicrobial activity of the complexes was tested
against four different microorganisms (Escherichia coli, Xanthomonas campestris,
Staphylococcus aureus and Bacillus subtilis) and was found similar or higher than
that of free Hsf. The binding of the complexes to calf-thymus DNA was monitored
by UV-vis spectroscopy and DNA-viscosity measurements and indirectly by
competitive studies with ethidium bromide; intercalation is suggested as the most
possible interaction mode. Fluorescence emission spectroscopy was used to
evaluate the interaction of the complexes with human or bovine serum albumin and
the corresponding binding constants were determined.
PMID- 27501349
TI - TbLOK1/ATOM19 is a novel subunit of the noncanonical mitochondrial outer membrane
protein translocase of Trypanosoma brucei.
AB - TbLOK1 has previously been characterized as a trypanosomatid-specific
mitochondrial outer membrane protein whose ablation caused a collapse of the
mitochondrial network, disruption of the membrane potential and loss of
mitochondrial DNA. Here we show that ablation of TbLOK1 primarily abolishes
mitochondrial protein import, both in vivo and in vitro. Co-immunprecipitations
together with blue native gel analysis demonstrate that TbLOK1 is a stable and
stoichiometric component of the archaic protein translocase of the outer membrane
(ATOM), the highly diverged functional analogue of the TOM complex in other
organisms. Furthermore, we show that TbLOK1 together with the other ATOM subunits
forms a complex functional network where ablation of individual subunits either
causes degradation of a specific set of other subunits or their exclusion from
the ATOM complex. In summary these results establish that TbLOK1 is an essential
novel subunit of the ATOM complex and thus that its primary molecular function is
linked to mitochondrial protein import across the outer membrane. The previously
described phenotypes can all be explained as consequences of the lack of
mitochondrial protein import. We therefore suggest that in line with the
nomenclature of the ATOM complex subunits, TbLOK1 should be renamed to ATOM19.
PMID- 27501350
TI - Costs of resistance and correlational selection in the multiple-herbivore
community of Solanum carolinense.
PMID- 27501353
TI - Response to the Article "Multi-Ethnic Attitudes Toward Physician-Assisted Death
in California and Hawai'i:" Selection of Respondents Creates Fatally Flawed
Study.
PMID- 27501352
TI - Eculizumab Therapy for Chronic Antibody-Mediated Injury in Kidney Transplant
Recipients: A Pilot Randomized Controlled Trial.
AB - We hypothesized that de novo donor-specific antibody (DSA) causes complement
dependent endothelial cell injury in kidney transplants, as assessed by
expression of endothelial cell-associated transcripts (ENDATs), that may be
attenuated through complement inhibition. In total, 15 participants (five
control, 10 treatment) with DSA and deteriorating renal function were enrolled.
The treatment group received 6 mo of eculizumab followed by 6 mo of observation,
whereas controls were observed. The primary end point was percentage change in
estimated GFR (eGFR) trajectory over the treatment period. The treatment group
had an improved eGFR trajectory versus control, based on our predetermined two
sided 0.10 significance level (p = 0.09). Within-subject analysis of treated
participants at 6-mo intervals did not show significant change (p = 0.60).
Modeling C1q status showed that C1q-positive patients had significantly higher
mean eGFR than patients with negative C1q (p = 0.04). Biopsies revealed elevated
renal ENDATs in most participants, but ENDATs were not reduced with complement
inhibition. Our data suggest that eculizumab treatment may stabilize kidney
function in patients with chronic persistent DSA based on our pilot a priori
significance threshold. ENDAT expression predicative of acute humoral injury is
not reduced with complement inhibition in this chronic setting. Further studies
will be necessary to determine which patients may benefit from eculizumab.
PMID- 27501351
TI - Divergence in Ubiquitin Interaction and Catalysis among the Ubiquitin-Specific
Protease Family Deubiquitinating Enzymes.
AB - Deubiquitinating enzymes (DUBs) are responsible for reversing mono- and
polyubiquitination of proteins and play essential roles in numerous cellular
processes. Close to 100 human DUBs have been identified and are classified into
five families, with the ubiquitin-specific protease (USP) family being the
largest (>50 members). The binding of ubiquitin (Ub) to USP is strikingly
different from that observed for the DUBs in the ubiquitin C-terminal hydrolase
(UCH) and ovarian tumor domain protease (OTU) families. We generated a panel of
mutant ubiquitins and used them to probe the ubiquitin's interaction with a
number of USPs. Our results revealed a remarkable divergence of USP-Ub
interactions among the USP catalytic domains. Our double-mutant cycle analysis
targeting the ubiquitin residues located in the tip, the central body, and the
tail of ubiquitin also demonstrated different crosstalk among the USP-Ub
interactions. This work uncovered intriguing divergence in the ubiquitin-binding
mode in the USP family DUBs and raised the possibility of targeting the ubiquitin
binding hot spots on USPs for selective inhibition of USPs by small molecule
antagonists.
PMID- 27501354
TI - FTY720P inhibits hepatic Na(+)-K(+) ATPase via S1PR2 and PGE2.
AB - Sphingosine-1-phosphate (S1P) was found previously to inhibit Na(+)-K(+) ATPase
in HepG2 cells. Whether fingolimod (FTY720), a S1P receptor (S1PR) agonist,
similarly inhibits the ATPase is a question that needs to be addressed. The aim
of this work was to study the effect of FTY720P, the active form of the drug, on
the activity of Na(+)-K(+) ATPase in HepG2 cells and determine its mechanism of
action. The activity of the ATPase was assayed by measuring the amount of
inorganic phosphate liberated in the presence and the absence of ouabain. FTY720
P (7.5 nmol/L, 15 min) significantly reduced the activity of the ATPase. This
effect disappeared completely in the presence of JTE-013, which is a specific
blocker of sphingosine-1-phosphate receptor 2 (S1PR2), as well as in the presence
of calphostin and indomethacin, which are inhibitors of protein kinase C (PKC)
and COX-2, respectively. The effect of FTY720P was mimicked by prostaglandin E2
(PGE2) and PMA, but abrogated by NF-kappaB inhibition. When NF-kappaB was
inhibited, the effect of exogenous PGE2 still appeared, but that of PMA did not
manifest, suggesting that NF-kappaB is upstream of PGE2 and downstream of PKC. It
was concluded that FTY720P activates via S1PR2, PKC, and NF-kappaB. The latter
induces PGE2 generation and inhibits Na(+)-K(+) ATPase.
PMID- 27501355
TI - A Simple Dewar/Cryostat for Thermally Equilibrating Samples at Known Temperatures
for Accurate Cryogenic Luminescence Measurements.
AB - The design and operation of a simple liquid nitrogen Dewar/cryostat apparatus
based upon a small fused silica optical Dewar, a thermocouple assembly, and a CCD
spectrograph are described. The experiments for which this Dewar/cryostat is
designed require fast sample loading, fast sample freezing, fast alignment of the
sample, accurate and stable sample temperatures, and small size and portability
of the Dewar/cryostat cryogenic unit. When coupled with the fast data acquisition
rates of the CCD spectrograph, this Dewar/cryostat is capable of supporting
cryogenic luminescence spectroscopic measurements on luminescent samples at a
series of known, stable temperatures in the 77-300 K range. A temperature
dependent study of the oxygen quenching of luminescence in a rhodium(III)
transition metal complex is presented as an example of the type of investigation
possible with this Dewar/cryostat. In the context of this apparatus, a stable
temperature for cryogenic spectroscopy means a luminescent sample that is
thermally equilibrated with either liquid nitrogen or gaseous nitrogen at a known
measureable temperature that does not vary (DeltaT < 0.1 K) during the short time
scale (~1-10 sec) of the spectroscopic measurement by the CCD. The Dewar/cryostat
works by taking advantage of the positive thermal gradient dT/dh that develops
above liquid nitrogen level in the Dewar where h is the height of the sample
above the liquid nitrogen level. The slow evaporation of the liquid nitrogen
results in a slow increase in h over several hours and a consequent slow increase
in the sample temperature T over this time period. A quickly acquired
luminescence spectrum effectively catches the sample at a constant, thermally
equilibrated temperature.
PMID- 27501357
TI - Are We All in the Same Boat? The Role of Perceptual Distance in Organizational
Health Interventions.
AB - The study investigates how agreement between leaders' and their team's
perceptions influence intervention outcomes in a leadership-training intervention
aimed at improving organizational learning. Agreement, i.e. perceptual distance
was calculated for the organizational learning dimensions at baseline. Changes in
the dimensions from pre-intervention to post-intervention were evaluated using
polynomial regression analysis with response surface analysis. The general
pattern of the results indicated that the organizational learning improved when
leaders and their teams agreed on the level of organizational learning prior to
the intervention. The improvement was greatest when the leader's and the team's
perceptions at baseline were aligned and high rather than aligned and low. The
least beneficial scenario was when the leader's perceptions were higher than the
team's perceptions. These results give insights into the importance of comparing
leaders' and their team's perceptions in intervention research. Polynomial
regression analyses with response surface methodology allow three-dimensional
examination of relationship between two predictor variables and an outcome. This
contributes with knowledge on how combination of predictor variables may affect
outcome and allows studies of potential non-linearity relating to the outcome.
Future studies could use these methods in process evaluation of interventions.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501356
TI - Neural Correlates and Connectivity Underlying Stress-Related Impulse Control
Difficulties in Alcoholism.
AB - BACKGROUND: Stress triggers impulsive and addictive behaviors, and alcoholism has
been frequently associated with increased stress sensitivity and impulse control
problems. However, neural correlates underlying the link between alcoholism and
impulsivity in the context of stress in patients with alcohol use disorders (AUD)
have not been well studied. METHODS: This study investigated neural correlates
and connectivity patterns associated with impulse control difficulties in
abstinent AUD patients. Using functional magnetic resonance imaging, brain
responses of 37 AUD inpatients, and 37 demographically matched healthy controls
were examined during brief individualized imagery trials of stress, alcohol cue,
and neutral-relaxing conditions. Stress-related impulsivity was measured using a
subscale score of impulse control problems from Difficulties in Emotion
Regulation Scale. RESULTS: Impulse control difficulties in AUD patients were
significantly associated with hypo-active response to stress in the ventromedial
prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to
the neutral condition (p < 0.01, whole-brain corrected). These regions were used
as seed regions to further examine the connectivity patterns with other brain
regions. With the VmPFC seed, AUD patients showed reduced connectivity with the
anterior cingulate cortex compared to controls, which are core regions of emotion
regulation, suggesting AUD patients' decreased ability to modulate emotional
response under distressed state. With the right caudate seed, patients showed
increased connectivity with the right motor cortex, suggesting increased tendency
toward habitually driven behaviors. With the left LPFC seed, decreased
connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with
sensory and motor cortices were found in AUD patients compared to controls (p <
0.05, whole-brain corrected). Reduced connectivity between the left LPFC and
DmPFC was further associated with increased stress-induced anxiety in AUD
patients (p < 0.05, with adjusted Bonferroni correction). CONCLUSIONS: Hypo
active response to stress and altered connectivity in key emotion regulatory
regions may account for greater stress-related impulse control problems in
alcoholism.
PMID- 27501358
TI - Potential Corticomotor Plasticity in Those with and without Chronic Ankle
Instability.
AB - INTRODUCTION: Quantifying corticomotor alterations is important to understand the
neurophysiological mechanisms that likely contribute to the neuromuscular control
deficits observed in patients with chronic ankle instability (CAI). Corticomotor
output mapping provides further insight into the changes within the motor cortex
and identifies potential changes in the area of the motor cortex associated with
selected muscles. Therefore, this investigation compared the corticomotor map
output for the fibularis longus (FL) muscle in patients with and without CAI.
METHODS: Eighteen CAI patients and 16 healthy controls (HC) volunteered.
Transcranial magnetic stimulation was used to map the motor cortex's
representation of the FL. The normalized average of three motor evoked potentials
at 100% of active motor threshold intensity was recorded for each scalp site on a
6 * 6 cm grid. Corticomotor output map was compared between groups through 1) the
size of the corticomotor map area, 2) the volume of the corticomotor map, and 3)
the location of cortical representation. Independent t-tests were used to assess
group differences in each mapping outcome variable. Cohen's d effect sizes along
with 95% confidence intervals were calculated using the pooled SD values.
RESULTS: CAI patients exhibited less map volume (P = 0.018, CAI = 8.2 +/- 3.2 cm
mV vs HC = 11.3 +/- 3.9 cm mV) and map area (P = 0.046, CAI = 12.8 +/- 6.0 cm vs
HC: 17.4 +/- 6.9 cm) compared with HC. CONCLUSIONS: The smaller map area and
volume suggest a more concentrated area of neurons communicating with the FL
muscle in patients with CAI. Consequently, motor cortical cells on the border of
the FL excitation area are less committed to the proper function of the FL muscle
and may be recruited by other surrounding areas. This may explain altered
movement strategies that lead to ankle reinjury.
PMID- 27501359
TI - Lower Extremity Stiffness Changes after Concussion in Collegiate Football
Players.
AB - PURPOSE: Recent research indicates that a concussion increases the risk of
musculoskeletal injury. Neuromuscular changes after concussion might contribute
to the increased risk of injury. Many studies have examined gait postconcussion,
but few studies have examined more demanding tasks. This study compared changes
in stiffness across the lower extremity, a measure of neuromuscular function,
during a jump-landing task in athletes with a concussion (CONC) to uninjured
athletes (UNINJ). METHODS: Division I football players (13 CONC and 26 UNINJ)
were tested pre- and postseason. A motion capture system recorded subjects
jumping on one limb from a 25.4-cm step onto a force plate. Hip, knee, and ankle
joint stiffness were calculated from initial contact to peak joint flexion using
the regression line slopes of the joint moment versus the joint angle plots. Leg
stiffness was (peak vertical ground reaction force [PVGRF]/lower extremity
vertical displacement) from initial contact to peak vertical ground reaction
force. All stiffness values were normalized to body weight. Values from both
limbs were averaged. General linear models compared group (CONC, UNINJ)
differences in the changes of pre- and postseason stiffness values. RESULTS:
Average time from concussion to postseason testing was 49.9 d. The CONC group
showed an increase in hip stiffness (P = 0.03), a decrease in knee (P = 0.03) and
leg stiffness (P = 0.03), but no change in ankle stiffness (P = 0.65) from pre-
to postseason. CONCLUSION: Lower extremity stiffness is altered after concussion,
which could contribute to an increased risk of lower extremity injury. These data
provide further evidence of altered neuromuscular function after concussion.
PMID- 27501360
TI - High-Speed Cycling Intervention Improves Rate-Dependent Mobility in Older Adults.
AB - PURPOSE: The aim was to determine the feasibility of a 6-wk speed-based exercise
program that could be used to initiate new exercise behaviors and to improve
rapid movement in older adults approaching frailty. METHODS: The intervention
group included 14 older adults (3 males and 11 females; mean +/- SD, age = 70 +/-
7.6 yr, height = 1.6 +/- 0.11 m, mass = 76.8 +/- 12.0 kg, body mass index = 27.7
+/- 4.7 kg.m). The control group included 12 older adults (6 males and 6 females;
mean +/- SD, age = 69.2 +/- 6.9 yr, height = 1.7 +/- 0.09 m, mass = 78.2 +/- 10.9
kg, body mass index = 25.3 +/- 2.7 kg.m). Subjects included active older adults,
including regular exercisers, but none were engaged in sports or exercises with
an emphasis on speed (e.g., cycling spin classes or tennis). Stationary recumbent
cycling was selected to minimize fall risk, and low pedaling resistance reduced
musculoskeletal and cardiovascular load. Two weekly 30-min exercise sessions
consisted of interval training in which subjects pedaled at preferred cadence and
performed ten 20-s fast cadence intervals separated by 40 s of active recovery at
preferred cadence. RESULTS: Significant group-time interactions (P < 0.05)
supported a 2-s improvement in the timed up and go test and a 34% improvement in
rapid isometric knee extension contractions in the exercise group but not in
controls. Central neural adaptations are suggested because this lower extremity
exercise program also elicited significant improvements in the untrained upper
extremities of the exercise group (elbow extension rate of force development
scaling factor and Nine-Hole Peg Test, P < 0.05). CONCLUSION: These results
demonstrate that a relatively low dose of speed-based exercise can improve
neuromuscular function and tests of mobility in older adults. Such a program
serves as a sensible precursor to subsequent, more vigorous training or as an
adjunct to a program where a velocity emphasis is lacking.
PMID- 27501361
TI - The Effect of Age on the VO2max Response to High-Intensity Interval Training.
AB - PURPOSE: High-intensity interval training (HIIT) is documented to yield effective
improvements in the cardiovascular system and be an excellent strategy for
healthy aging. However, it is not determined how age may affect the training
response of key components of aerobic endurance. METHODS: We recruited 72 males
(mean +/- SD, weight = 84.9 +/- 12.9 kg, height = 180.4 +/- 5.8 cm) and 22
females (weight = 76.0 +/- 17.2 kg, height = 171.2 +/- 6.7 cm) from 20 to 70+ yr
with a training status typical for their age group and divided them into six
decade cohorts. The participants followed supervised training with a targeted
intensity of 90%-95% of maximal HR (HRmax) three times a week for 8 wk. RESULTS:
After HIIT, all age groups increased (P < 0.001-P = 0.004) maximal oxygen
consumption (VO2max) with 0.39 +/- 0.20 (20-29 yr), 0.28 +/- 0.21 (30-39 yr),
0.36 +/- 0.08 (40-49 yr), 0.34 +/- 0.27 (50-59 yr), 0.33 +/- 0.23 (60-69 yr), and
0.34 +/- 0.14 (70+ yr) L.min, respectively. These 9%-13% improvements were not
significantly different between the age groups. In contrast to age, the
percentage improvements after HIIT were inversely associated with baseline
training status (r = 0.66, P < 0.001). HRmax was not altered within the
respective age cohorts, but the two oldest cohorts exhibited a tendency (P =
0.07) to increase HRmax in contrast to a training-induced decrease in the younger
cohorts. CONCLUSION: In healthy individuals with an aerobic capacity typical for
what is observed in the population, the training response is likely not affected
by age in a short-term training intervention but may rather be affected by the
initial training status. These findings imply that individuals across age all
have a great potential for cardiovascular improvements, and that HIIT may be used
as an excellent strategy for healthy aging.
PMID- 27501362
TI - Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes.
AB - Prion diseases result from the misfolding of the normal, cellular prion protein
(PrP(C)) to an abnormal protease resistant isomer called PrP(Res). The emergence
of prion diseases in wildlife populations and their increasing threat to human
health has led to increased efforts to find a treatment for these diseases.
Recent studies have found numerous anti-prion compounds that can either inhibit
the infectious PrP(Res) isomer or down regulate the normal cellular prion
protein. However, most of these compounds do not cross the blood brain barrier to
effectively inhibit PrP(Res) formation in brain tissue, do not specifically
target neuronal PrP(C), and are often too toxic to use in animal or human
subjects. We investigated whether siRNA delivered intravascularly and targeted
towards neuronal PrP(C) is a safer and more effective anti-prion compound. This
report outlines a protocol to produce two siRNA liposomal delivery vehicles, and
to package and deliver PrP siRNA to neuronal cells. The two liposomal delivery
vehicles are 1) complexed-siRNA liposome formulation using cationic liposomes
(LSPCs), and 2) encapsulated-siRNA liposome formulation using cationic or anionic
liposomes (PALETS). For the LSPCs, negatively charged siRNA is electrostatically
bound to the cationic liposome. A positively charged peptide (RVG-9r [rabies
virus glycoprotein]) is added to the complex, which specifically targets the
liposome-siRNA-peptide complexes (LSPCs) across the blood brain barrier (BBB) to
acetylcholine expressing neurons in the central nervous system (CNS). For the
PALETS (peptide addressed liposome encapsulated therapeutic siRNA), the cationic
and anionic lipids were rehydrated by the PrP siRNA. This procedure results in
encapsulation of the siRNA within the cationic or anionic liposomes. Again, the
RVG-9r neuropeptide was bound to the liposomes to target the siRNA/liposome
complexes to the CNS. Using these formulations, we have successfully delivered
PrP siRNA to AchR-expressing neurons, and decreased the PrP(C) expression of
neurons in the CNS.
PMID- 27501363
TI - Amyloid beta attenuates metabotropic zinc sensing receptor, mZnR/GPR39, dependent
Ca2+ , ERK1/2 and Clusterin signaling in neurons.
AB - A hallmark of Alzheimer's disease is accumulation of amyloid beta (Abeta)
deposits, which are associated with neuronal dysfunction, spine loss, and
impaired Ca2+ homeostasis. Amyloid beta (Abeta) binds to and is aggregated by
Zn2+ , a metal released from synaptic glutamatergic vesicles during neuronal
activity. Synaptically released Zn2+ activates a metabotropic Gq-coupled Zn2+
sensing receptor, mZnR/GPR39, and induces Ca2+ -signaling in post-synaptic
neurons. We examined if Abeta, as a Zn2+ binding protein, regulates neuronal Zn2+
-signaling mediated by mZnR/GPR39 using SHSY-5Y cells and cortical neurons from
GPR39 wild-type and knockout mice. Following acute or chronic treatment with
Abeta neuronal Zn2+ -dependent Ca2+ release via mZnR/GPR39 is significantly
reduced. This impairment is overcome when excess Zn2+ is applied, suggesting that
impaired Ca2+ -signaling results from Abeta binding of Zn2+ . The Zn2+ -dependent
mZnR/GPR39 activation triggers phosphorylation of extracellular regulated kinase
and up-regulates expression of the chaperone protein clusterin (Clu).
Importantly, neuronal Zn2+ -dependent extracellular regulated kinase1/2
phosphorylation and up-regulation of Clu are attenuated by silencing mZnR/GPR39
as well as by Abeta treatment. In contrast, Zn2+ -dependent AKT phosphorylation
is not mediated by mZnR/GPR39 and is not attenuated by Abeta treatment. Thus,
Zn2+ signaling via mZnR/GPR39 is distinctively disrupted by a critical
pathological component of Alzheimer's disease. Synaptically released Zn2+
activates a Zn2+ -sensing receptor, mZnR/GPR39, and induces Ca2+ -signaling,
followed by ERK1/2 MAPK activation and up-regulation of clusterin. Amyloid beta
(Abeta) binds to Zn2+ thus forming oligomers that are a hallmark of Alzheimer's
disease. We show that Abeta attenuates Zn2+ -dependent Ca2+ -responses, abolishes
ERK1/2 activation and down-regulates clusterin expression. Thus, Zn2+ signaling
via mZnR/GPR39 is disrupted by Abeta, a critical pathological component of
Alzheimer's disease.
PMID- 27501364
TI - The influence of intercalating perfluorohexane into lipid shells on nano and
microbubble stability.
AB - Microbubbles are potential diagnostic and therapeutic agents. In vivo stability
is important as the bubbles are required to survive multiple passages through the
heart and lungs to allow targeting and delivery. Here we have systematically
varied key parameters affecting microbubble lifetime to significantly increase in
vivo stability. Whilst shell and core composition are found to have an important
role in improving microbubble stability, we show that inclusion of small
quantities of C6F14 in the microbubble bolus significantly improves microbubble
lifetime. Our results indicate that C6F14 inserts into the lipid shell,
decreasing surface tension to 19 mN m(-1), and increasing shell resistance, in
addition to saturating the surrounding medium. Surface area isotherms suggest
that C6F14 incorporates into the acyl chain region of the lipid at a high molar
ratio, indicating ~2 perfluorocarbon molecules per 5 lipid molecules. The
resulting microbubble boluses exhibit a higher in vivo image intensity compared
to commercial compositions, as well as longer lifetimes.
PMID- 27501365
TI - Compositional Analysis of Asymmetric and Symmetric Dimethylated H3R2 Using Liquid
Chromatography-Tandem Mass Spectrometry-Based Targeted Proteomics.
AB - Protein arginine methylation is one of the common post-translational
modifications in cellular processes. To date, two isomeric forms of dimethylated
arginine have been identified: asymmetric N(G),N(G)-dimethylarginine (aDMA), and
symmetric N(G),N'(G)-dimethylarginine (sDMA). Evidence indicated that these
isomers can coexist and have different or even opposite functions, with aDMA and
sDMA forms of arginine 2 on histone H3 (i.e., H3R2me2a and H3R2me2s) being an
example. Thus, specific detection and quantification of each isomeric form is
important. Current methods are capable of predicting and detecting thousands of
methylarginine sites in proteins, whereas differentiation and stoichiometric
measurement of dimethylated protein isomers are still challenging. Liquid
chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted
proteomics has emerged as a promising technique for site-specific quantification
of protein methylation using enzymatic peptides as surrogates of target proteins.
However, it should be pointed out that a routine targeted proteomics strategy
cannot easily distinguish sDMA- and aDMA-containing surrogate peptides due to
their common nature. The estimated amount should be considered as the sum of both
arginine dimethylated isomers. In this study, compositional analysis based on a
linear algebra algorithm as an add-on to targeted proteomics was employed to
quantify H3R2me2a and H3R2me2s (i.e., surrogate peptides of AR(me2a)TK(me1/2)QT
and AR(me2s)TK(me1/2)QT). To achieve this simultaneous quantification, a targeted
proteomics assay was developed and validated for each isomer first. With the
slope and intercept of their calibration curves for each multiple reaction
monitoring (MRM) transition, linear algebraic equations were derived. Using a
series of mock mixtures consisting of isomers in varying concentrations, the
reliability of the method was confirmed. Finally, the H3R2 dimethylation status
was analyzed in normal MCF-10A cells, parental drug-sensitive MCF-7/WT cancer
cells, and drug-resistant MCF-7/ADR cancer cells. Dimethylated H3R2 was also
monitored in MCF-7/WT cells with the treatment of doxorubicin (DOX) for
confirmation.
PMID- 27501366
TI - Generalized Valence Bond Description of Chalcogen-Nitrogen Compounds. III. Why
the NO-OH and NS-OH Bonds Are So Different.
AB - Crabtree et al. recently reported the microwave spectrum of nitrosyl-O-hydroxide
(trans-NOOH), an isomer of nitrous acid, and found that this molecule has the
longest O-O bond ever observed: 1.9149 A +/- 0.0005 A. This is in marked contrast
to the structure of the valence isoelectronic trans-NSOH molecule, which has a
normal NS-OH bond length and strength. Generalized valence bond calculations show
that the long bond in trans-NOOH is the result of a weak through-pair interaction
that singlet couples the spins of the electrons in singly occupied orbitals on
the hydroxyl radical and nitrogen atom, an interaction that is enhanced by the
intervening lone pair of the oxygen atom in NO. The NS-OH bond is the result of
the formation of a stable recoupled pair bond dyad, which accounts for both its
length and strength.
PMID- 27501367
TI - Sensitivity of breeding values for carcass traits of meat-type quail to changes
in dietary (methionine + cystine):lysine ratio using reaction norm models.
AB - Our objective was to evaluate changes in breeding values for carcass traits of
two meat-type quail (Coturnix coturnix) strains (LF1 and LF2) to changes in the
dietary (methionine + cystine):lysine ([Met + Cys]:Lys) ratio due to genotype by
environment (G * E) interaction via reaction norm. A total of 7000 records of
carcass weight and yield were used for analyses. During the initial phase (from
hatching to day 21), five diets with increasing (Met + Cys):Lys ratios (0.61,
0.66, 0.71, 0.76 and 0.81), containing 26.1% crude protein and 2900 kcal ME/kg,
were evaluated. Analyses were performed using random regression models that
included linear functions of sex (fixed effect) and breeding value (random
effect) for carcass weight and yield, without and with heterogeneous residual
variance adjustment. Both fixed and random effects were modelled using Legendre
polynomials of second order. Genetic variance and heritability estimates were
affected by both (Met + Cys):Lys ratio and strain. We observed that a G * E
interaction was present, with changes in the breeding value ranking. Therefore,
genetic evaluation for carcass traits should be performed under the same (Met +
Cys):Lys ratio in which quails are raised.
PMID- 27501368
TI - Inhibitor development in two cousins receiving full-length factor VIII (FVIII)
and FVIII-Fc fusion protein.
PMID- 27501369
TI - Development and Validation of the Chinese Triarchic Psychopathy Measure.
AB - The nature of psychopathy is not well understood in East Asian cultures,
partially due to a lack of an established measurement of this important
construct. This study developed and validated a Chinese-language version of the
Triarchic Psychopathy Measure (TriPM) based on Patrick et al.'s (2009) triarchic
model of psychopathy. Study 1 described the translation of the Chinese TriPM and
demonstrated that the Chinese version of the TriPM is equivalent to the original
English version in linguistic meaning. Study 2 examined the construct validity of
the Chinese TriPM in a Chinese student sample. The TriPM evinced acceptable
reliability and promising validity. Moreover, cross-cultural equivalence was
examined by relative associations for the TriPM with the Levenson Self-Report
Psychopathy Scale across the Chinese sample and a comparable United States
student sample. Results revealed that the test bias in the strength of
associations, regression intercepts, and slopes was mostly absent across the two
samples.
PMID- 27501370
TI - Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for
Unresectable Metastases Confined to the Liver.
AB - Unresectable liver metastases of colorectal cancer can be treated with systemic
chemotherapy, aiming to limit the disease, extend survival or turn unresectable
metastases into resectable ones. Some patients however, suffer from side effects
or progression under systemic treatment. For patients with metastasized uveal
melanoma there are no standard systemic therapy options. For patients without
extrahepatic disease, isolated liver perfusion (IHP) may enable local disease
control with limited systemic side effects. Previously, this was performed during
open surgery with satisfying results, but morbidity and mortality related to the
open procedure, prohibited a widespread application. Therefore, percutaneous
hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides
decreasing morbidity and mortality, this procedure can be repeated, hopefully
leading to a higher response rate and improved survival (by local control of
disease). During PHP, catheters are placed in the proper hepatic artery, to
infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the
chemosaturated blood returning through the hepatic veins. The caval vein catheter
is a double balloon catheter that prohibits leakage into the systemic
circulation. The blood returning from the hepatic veins is aspirated through the
catheter fenestrations and then perfused through an extra-corporeal filtration
system. After filtration, the blood is returned to the patient by a third
catheter in the right internal jugular vein. During PHP a high dose of melphalan
is infused into the liver, which is toxic and would lead to life threatening
complications when administered systemically. Because of the significant
hemodynamic instability resulting from the combination of caval vein occlusion
and chemofiltration, hemodynamic monitoring and hemodynamic support is of
paramount importance during this complex procedure.
PMID- 27501371
TI - Bioresorbable scaffold-the holy grail of percutaneous coronary intervention: fact
or myth?
PMID- 27501372
TI - Single- and dual-wavelength photodetectors with MgZnO/ZnO metal-semiconductor
metal structure by varying the bias voltage.
AB - By varying the bias voltage of an Mg x Zn1-x O/ZnO metal-semiconductor-metal
photodetector (MSM-PDs), the detection wavelength can be modulated from a single
to a dual wavelength. A long-wavelength band response is caused by the ZnO
absorption and a short-wavelength band response is caused by Mg x Zn1-x O. At a 0
V bias voltage, the photogenerated electrons in ZnO are confined to the Mg x Zn1
x O/ZnO interface, arising from the piezoelectric polarization. The accumulated
electrons hop the Mg x Zn1-x O layer through the assistance of defects; however,
the photogenerated electrons in Mg x Zn1-x O cannot cross over the large barrier
height at the Au/MgZnO interface, resulting in a single-wavelength photodetector
with a long-wavelength band (345-400 nm) having a peak wavelength of 370 nm. By
increasing the bias voltage to 1-2 V, the barrier height is lowered, enabling the
photogenerated electrons in Mg x Zn1-x O to easily cross over the low barrier
height, leading to dual-wavelength photodetectors having peak wavelengths of 370
and 340 nm. On further increasing the bias voltage beyond 2 V, the photogenerated
electrons in ZnO sink deeply in the hollow at the Mg x Zn1-x O/ZnO interface
owing to the large applied voltage. These electrons are effectively confined at
the Mg x Zn1-x O/ZnO interface, which retards the tunneling of the photogenerated
electrons in ZnO through the Mg x Zn1-x O layer; hence the MSM-PDs revert back to
single wavelength photodetectors; however, the detection wavelength is different
from that of the MSM-PDs biased at 0 V. Instead of having a long-wavelength band
(345-400 nm), the MSM-PDs demonstrate a short-wavelength band (320-345 nm) at a 3
V bias voltage.
PMID- 27501373
TI - Thiophene-Fused pi-Systems from Diarylacetylenes and Elemental Sulfur.
AB - A simple yet effective method for the formation of thiophene-fused pi-systems is
reported. When arylethynyl-substituted polycyclic arenes were heated in DMF in
the presence of elemental sulfur, the corresponding thiophene-fused polycyclic
arenes were obtained via cleavage of the ortho-C-H bond. Thus, arylethynylated
naphthalenes, fluoranthenes, pyrenes, corannulenes, chrysenes, and
benzo[c]naphtho[2,1-p]chrysenes were effectively converted into the corresponding
thiophene-fused pi-systems. Apart from polycyclic hydrocarbons, thiophene
derivatives are also susceptible to this reaction. The practical utility of this
reaction is demonstrated by preparations on the decagram scale, one-pot two-step
reaction sequences, and multiple thiophene annulations.
PMID- 27501375
TI - Long-term preclinical magnetic resonance imaging alterations in sporadic
Creutzfeldt-Jakob disease.
AB - An asymptomatic 74-year-old woman, on follow-up for a carotid body tumor, showed
magnetic resonance imaging (MRI) focal restricted diffusion confined to the left
temporal and occipital cortices. Thirteen months later, diffusion-weighted images
revealed a bilateral cortical ribbon sign involving all lobes. After 1 month, the
patient developed gait instability and cognitive decline rapidly evolving to
severe dementia and death within 3 months. Prion protein gene sequence,
molecular, and neuropathological studies confirmed the diagnosis of sporadic
Creutzfeldt-Jakob disease (sCJD) MM1 subtype. Here we show the kinetics of MRI
changes and prion spreading in preclinical sCJD MM1. Ann Neurol 2016;80:629-632.
PMID- 27501374
TI - Promising therapies for treatment of nonalcoholic steatohepatitis.
AB - INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has become the most
common etiology for abnormal aminotransferase levels and chronic liver disease.
Its growing prevalence is largely linked to the presence of metabolic syndrome,
particularly diabetes and insulin resistance. It is estimated that 60-80% of the
type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions
ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset
of patients with hepatic steatosis progress to NASH, while 15-20% of patients
with NASH develop cirrhosis. This progression is thought to be multifactorial,
and there are currently no FDA-approved medications for the treatment of NASH.
AREAS COVERED: We review drugs currently in Phase II and III clinical trials for
treatment of NAFLD and NASH, including their mechanisms of action, relationship
to the pathophysiology of NASH, and rationale for their development. EXPERT
OPINION: The treatment of NASH is complex and necessitates targeting a number of
different pathways. Combination therapy, preferably tailored toward the disease
stage and severity, will be needed to achieve maximum therapeutic effect. With
multiple agents currently being developed, there may soon be an ability to
effectively slow or even reverse the disease process in many NAFLD/NASH patients.
PMID- 27501376
TI - From Planar to Cage in 15 Easy Steps: Resolving the C60H21F9(-) -> C60(-)
Transformation by Ion Mobility Mass Spectrometry.
AB - A combination of mass spectrometry, collision-induced dissociation, ion mobility
mass spectrometry (IM-MS), and density functional theory (DFT) has been used to
study the evolution of anionic species generated by laser-desorption of the near
planar, fluorinated polycyclic aromatic hydrocarbon (PAH), C60H21F9 (s). The
dominant decay process for isolated, thermally activated C60H21F9(-) species
comprises a sequence of multiple regioselective cyclodehydrofluorination and
cyclodehydrogenation reactions (eliminating HF and H2, respectively, while
forming additional pentagons and/or hexagons). The DFT calculations allow us to
set narrow bounds on the structures of the resulting fragment ions by fitting
structural models to experimentally determined collision cross sections. These
show that the transformation of the precursor anion proceeds via a series of
intermediate structures characterized by increasing curvature, ultimately leading
to the closed-shell fullerene cage C60(-) as preprogrammed by the precursor
structure.
PMID- 27501377
TI - Only when all contribute their firewood can they build up a big fire.
PMID- 27501379
TI - Endoscopic scoring indices for evaluation of disease activity in Crohn's disease.
AB - BACKGROUND: Endoscopic assessment of mucosal disease activity is widely used to
determine eligibility and response to therapy in clinical trials of treatment for
Crohn's disease. However, the operating properties of the currently available
endoscopic indices remain unclear. OBJECTIVES: A systematic review was undertaken
to evaluate the development and operating characteristics of the Crohn's Disease
Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Scale for Crohn's
Disease (SES-CD). SEARCH METHODS: Electronic searches of the MEDLINE (1966 to
December 2015), EMBASE (1980 to December 2015), and Cochrane CENTRAL Register of
Controlled Trials (Issue 12, 2015) databases were supplemented by manual reviews
of reference listings and conference proceedings (Digestive Disease Week, United
European Gastroenterology Week, European Crohn's and Colitis Organization).
SELECTION CRITERIA: Any study design (e.g. randomized controlled trials, cohort
studies, case series) that evaluated either or both the CDEIS or SES-CD in
patients with Crohn's disease was considered for inclusion. Eligible participants
were adult patients (> 16 years), diagnosed with Crohn's disease using
conventional clinical, radiographic, and endoscopic criteria. DATA COLLECTION AND
ANALYSIS: Two authors (RK, JKM) independently reviewed the titles and abstracts
of the studies identified from the literature search. The full texts of
potentially relevant citations were reviewed for inclusion and the study
investigators were contacted to clarify any unclear data. Any disagreements were
resolved by discussion and consensus with a third author. A standardized form was
used to assess eligibility of trials for inclusion in the study and for data
extraction.Two authors independently extracted and recorded data (RK, SAN). The
number of patients enrolled; number of patients per treatment arm; patient
characteristics including age and gender distribution; endoscopic index; and
outcomes such as intra-rater reliability, inter-rater reliability responsiveness,
validity, feasibility, construct validity, and criterion validity were recorded
for each trial. MAIN RESULTS: Forty-three reports of 30 studies fulfilled the
inclusion criteria.For the SES-CD, inter-rater reliability was assessed in four
studies. In the development study for the SES-CD (Daperno 2004), the overall ICC
(0.9815, 95% CI 0.9705 to 0.9884) and the kappa for the regions is high; however
the paired raters were in the same room which introduces the potential for
bias.For the CDEIS, inter-rater reliability was assessed in six studies. Daperno
2014 reported that the ICC for the CDEIS was 0.985 (95% CI 0.939-1.000) for
average measures of video score and was 0.835 (95% CI 0.540-0.995) for single
measures of video score.With respect to validity, correlation between the CDEIS
and clinical measures, including C-reactive protein (CRP) and erythrocyte
sedimentation rate (ESR), was also reported. The estimates of correlation with
CRP were r = 0.521 (Sipponen 2010b), r = 0.553 (Sipponen 2008a) and r = 0.608
(Sipponen 2008c). For the SES-CD, the corresponding values for correlation with
CRP ranged from r = 0.46 (Jones 2008) to r = 0.68 (Green 2011).Responsiveness
data for the CDEIS were available in nine studies. Seven studies demonstrated
statistically significant decreases in the CDEIS score after administration of a
treatment of known efficacy. Minimal responsiveness data were available for the
SES-CD. Sipponen 2010a and Sipponen 2010b demonstrated statistically significant
changes in the SES-CD score after subjects were administered a treatment of known
efficacy.No studies were identified that explicitly evaluated the feasibility for
either the SES-CD or the CDEIS. The SES-CD requires fewer calculations and may
therefore be easier to use than the CDEIS. AUTHORS' CONCLUSIONS: Although they
are used in clinical trials, the CDEIS and SES-CD remain incompletely validated.
Future research is required to determine the operating properties and to define
the optimal index.
PMID- 27501378
TI - Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506
in Rats.
AB - Immunosuppressive agents are used for the treatment of immune-mediated
myocarditis; however, the need to develop a more effective therapeutic approach
remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to
an inflammatory lesion with enhanced vascular permeability. The aims of this
study were to investigate the distribution of liposomal FK506, an
immunosuppressive drug encapsulated within liposomes, and the drug's effects on
cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We
prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 +/-
4.4 nm). We induced EAM by immunization with porcine myosin and assessed the
tissue distribution of the nano-sized beads and liposomal FK506 in this model.
After liposomal or free FK506 was administered on days 14 and 17 after
immunization, the cytokine expression in the rat hearts along with the
histological findings and hemodynamic parameters were determined on day 21. Ex
vivo fluorescent imaging revealed that intravenously administered fluorescent
labeled nano-sized beads had accumulated in myocarditic but not normal hearts on
day 14 after immunization and thereafter. Compared to the administration of free
FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when
liposomal FK506 was administered. The administration of liposomal FK506 markedly
suppressed the expression of cytokines, such as interferon-gamma and tumor
necrosis factor-alpha, and reduced inflammation and fibrosis in the myocardium on
day 21 compared to free FK506. The administration of liposomal FK506 also
markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano
sized liposomes may be a promising drug delivery system for targeting myocarditic
hearts with cardioprotective agents.
PMID- 27501380
TI - What distinguishes cyanobacteria able to revive after desiccation from those that
cannot: the genome aspect.
AB - Filamentous cyanobacteria are the main founders and primary producers in
biological desert soil crusts (BSCs) and are likely equipped to cope with one of
the harshest environmental conditions on earth including daily
hydration/dehydration cycles, high irradiance and extreme temperatures. Here, we
resolved and report on the genome sequence of Leptolyngbya ohadii, an important
constituent of the BSC. Comparative genomics identified a set of genes present in
desiccation-tolerant but not in dehydration-sensitive cyanobacteria. RT qPCR
analyses showed that the transcript abundance of many of them is upregulated
during desiccation in L. ohadii. In addition, we identified genes where the
orthologs detected in desiccation-tolerant cyanobacteria differs substantially
from that found in desiccation-sensitive cells. We present two examples, treS and
fbpA (encoding trehalose synthase and fructose 1,6-bisphosphate aldolase
respectively) where, in addition to the orthologs present in the desiccation
sensitive strains, the resistant cyanobacteria also possess genes with different
predicted structures. We show that in both cases the two orthologs are
transcribed during controlled dehydration of L. ohadii and discuss the genetic
basis for the acclimation of cyanobacteria to the desiccation conditions in
desert BSC.
PMID- 27501381
TI - Observing Mitotic Division and Dynamics in a Live Zebrafish Embryo.
AB - Mitosis is critical for organismal growth and differentiation. The process is
highly dynamic and requires ordered events to accomplish proper chromatin
condensation, microtubule-kinetochore attachment, chromosome segregation, and
cytokinesis in a small time frame. Errors in the delicate process can result in
human disease, including birth defects and cancer. Traditional approaches
investigating human mitotic disease states often rely on cell culture systems,
which lack the natural physiology and developmental/tissue-specific context
advantageous when studying human disease. This protocol overcomes many obstacles
by providing a way to visualize, with high resolution, chromosome dynamics in a
vertebrate system, the zebrafish. This protocol will detail an approach that can
be used to obtain dynamic images of dividing cells, which include: in vitro
transcription, zebrafish breeding/collecting, embryo embedding, and time-lapse
imaging. Optimization and modifications of this protocol are also explored. Using
H2A.F/Z-EGFP (labels chromatin) and mCherry-CAAX (labels cell membrane) mRNA
injected embryos, mitosis in AB wild-type, auroraB(hi1045) (,) and esco2(hi2865)
mutant zebrafish is visualized. High resolution live imaging in zebrafish allows
one to observe multiple mitoses to statistically quantify mitotic defects and
timing of mitotic progression. In addition, observation of qualitative aspects
that define improper mitotic processes (i.e., congression defects, missegregation
of chromosomes, etc.) and improper chromosomal outcomes (i.e., aneuploidy,
polyploidy, micronuclei, etc.) are observed. This assay can be applied to the
observation of tissue differentiation/development and is amenable to the use of
mutant zebrafish and pharmacological agents. Visualization of how defects in
mitosis lead to cancer and developmental disorders will greatly enhance
understanding of the pathogenesis of disease.
PMID- 27501383
TI - A purely predatory relationship... Really?
PMID- 27501382
TI - Design and implementation of embedded 8-channel receive-only arrays for whole
brain MRI and fMRI of conscious awake marmosets.
AB - PURPOSE: The common marmoset (Callithrix jacchus) is a New World primate of
increasing interest to neuroscience and in translational brain research. The
present work describes the design and implementation of individualized 8-channel
receive-only radiofrequency (RF) coil arrays that provide whole-brain coverage
and allow anatomical and functional MRI experiments in conscious, awake
marmosets. METHODS: The coil arrays were designed with their elements embedded
inside individualized restraint helmets. The size, geometry, and arrangement of
the coil elements were optimized to allow whole-brain coverage. Coil-to-coil
decoupling was achieved by a combination of geometric decoupling and low input
impedance preamplifiers. The performance of the embedded arrays was compared
against that of one 8-channel receive-only array built to fit the external
surface of the helmets. RESULTS: Three individualized helmets with embedded coil
arrays were built for three marmosets. Whole-brain coverage was achieved with
high sensitivity extending over the entire cortex. Visual stimulation of
conscious awake marmosets elicited robust BOLD fMRI responses in both primary and
higher order visual areas of the occipitotemporal cortex. CONCLUSION: The high
sensitivity provided by embedded receive-only coil arrays allows both anatomical
and functional MRI data to be obtained with high spatial resolution in conscious,
awake marmosets. Magn Reson Med 78:387-398, 2017. (c) 2016 International Society
for Magnetic Resonance in Medicine.
PMID- 27501384
TI - Evaluation of Nitrous Oxide Emission from Sulfide- and Sulfur-Based Autotrophic
Denitrification Processes.
AB - Recent studies have shown that sulfide- and sulfur-based autotrophic
denitrification (AD) processes play an important role in contributing to nitrous
oxide (N2O) production and emissions. However, N2O production is not recognized
in the current AD models, limiting their ability to predict N2O accumulation
during AD. In this work, a mathematical model is developed to describe N2O
dynamics during sulfide- and sulfur-based AD processes for the first time. The
model is successfully calibrated and validated using N2O data from two
independent experimental systems with sulfide or sulfur as electron donors for
AD. The model satisfactorily describes nitrogen reductions, sulfide/sulfur
oxidation, and N2O accumulation in both systems. Modeling results revealed
substantial N2O accumulation due to the relatively low N2O reduction rate during
both sulfide- and sulfur-based AD processes. Application of the model to simulate
long-term operations of activated sludge systems performing sulfide- and sulfur
based AD processes indicates longer sludge retention time reduced N2O emission.
For sulfide-based AD process, higher initial S/N ratio also decreased N2O
emission but with a higher operational cost. This model can be a useful tool to
support process operation optimization for N2O mitigation during AD with sulfide
or sulfur as electron donor.
PMID- 27501385
TI - A linguistic comparison between auditory verbal hallucinations in patients with a
psychotic disorder and in nonpsychotic individuals: Not just what the voices say,
but how they say it.
AB - BACKGROUND: Auditory verbal hallucinations (AVH) in psychotic patients are
associated with activation of right hemisphere language areas, although this
hemisphere is non-dominant in most people. Language generated in the right
hemisphere can be observed in aphasia patients with left hemisphere damage. It is
called "automatic speech", characterized by low syntactic complexity and negative
emotional valence. AVH in nonpsychotic individuals, by contrast, predominantly
have a neutral or positive emotional content and may be less dependent on right
hemisphere activity. We hypothesize that right hemisphere language
characteristics can be observed in the language of AVH, differentiating psychotic
from nonpsychotic individuals. METHOD: 17 patients with a psychotic disorder and
19 nonpsychotic individuals were instructed to repeat their AVH verbatim directly
upon hearing them. Responses were recorded, transcribed and analyzed for total
words, mean length of utterance, proportion of grammatical utterances, proportion
of negations, literal and thematic perseverations, abuses, type-token ratio,
embeddings, verb complexity, noun-verb ratio, and open-closed class ratio.
RESULTS: Linguistic features of AVH overall differed between groups
F(13,24)=3.920, p=0.002; Pillai's Trace 0.680. AVH of psychotic patients compared
with AVH of nonpsychotic individuals had a shorter mean length of utterance,
lower verb complexity, and more verbal abuses and perseverations (all p<0.05).
Other features were similar between groups. CONCLUSION: AVH of psychotic patients
showed lower syntactic complexity and higher levels of repetition and abuses than
AVH of nonpsychotic individuals. These differences are in line with a stronger
involvement of the right hemisphere in the origination of AVH in patients than in
nonpsychotic voice hearers.
PMID- 27501386
TI - How language flows when movements don't: An automated analysis of spontaneous
discourse in Parkinson's disease.
AB - To assess the impact of Parkinson's disease (PD) on spontaneous discourse, we
conducted computerized analyses of brief monologues produced by 51 patients and
50 controls. We explored differences in semantic fields (via latent semantic
analysis), grammatical choices (using part-of-speech tagging), and word-level
repetitions (with graph embedding tools). Although overall output was
quantitatively similar between groups, patients relied less heavily on action
related concepts and used more subordinate structures. Also, a classification
tool operating on grammatical patterns identified monologues as pertaining to
patients or controls with 75% accuracy. Finally, while the incidence of dysfluent
word repetitions was similar between groups, it allowed inferring the patients'
level of motor impairment with 77% accuracy. Our results highlight the relevance
of studying naturalistic discourse features to tap the integrity of neural (and,
particularly, motor) networks, beyond the possibilities of standard token-level
instruments.
PMID- 27501387
TI - Current Welfare Problems Facing Horses in Great Britain as Identified by Equine
Stakeholders.
AB - Despite growing concerns about the welfare of horses in Great Britain (GB) there
has been little surveillance of the welfare status of the horse population.
Consequently we have limited knowledge of the range of welfare problems
experienced by horses in GB and the situations in which poor welfare occurs.
Thirty-one in-depth interviews were conducted with a cross -section of equine
stakeholders, in order to explore their perceptions of the welfare problems faced
by horses in GB. Welfare problems relating to health, management and riding and
training were identified, including horses being under or over weight, stabling
24 hours a day and the inappropriate use of training aids. The interviewees also
discussed broader contexts in which they perceived that welfare was compromised.
The most commonly discussed context was where horses are kept in unsuitable
environments, for example environments with poor grazing. The racing industry and
travellers horses were identified as areas of the industry where horse welfare
was particularly vulnerable to compromise. Lack of knowledge and financial
constraints were perceived to be the root cause of poor welfare by many
interviewees. The findings give insight into the range of welfare problems that
may be faced by horses in GB, the contexts in which these may occur and their
possible causes. Many of the problems identified by the interviewees have
undergone limited scientific investigation pointing to areas where further
research is likely to be necessary for welfare improvement. The large number of
issues identified suggests that some form of prioritisation may be necessary to
target research and resources effectively.
PMID- 27501388
TI - Detailed Observation of Multiphoton Emission Enhancement from a Single Colloidal
Quantum Dot Using a Silver-Coated AFM Tip.
AB - The enhancement of multiphoton emission from a single colloidal nanocrystal
quantum dot (NQD) interacting with a plasmonic nanostructure was investigated
using a silver-coated atomic force microscopy tip (AgTip) as the plasmonic
nanostructure. Using the AgTip, which exhibited a well-defined localized surface
plasmon (LSP) resonance band, we controlled the spectral overlap and the distance
between the single NQD and the AgTip. The emission behavior of the single NQD
when approaching the AgTip at the nanometer scale was measured using off
resonance (405 nm) and resonance (465 nm) excitation of the LSP. We directly
observed the conversion of the single-photon emission from a single NQD to
multiphoton emission with reduction of the emission lifetime at both excitation
wavelengths as the NQD-AgTip distance decreased, whereas a decrease and increase
in the emission intensity were observed at 405 and 465 nm excitation,
respectively. By combining theoretical analysis and the numerical simulation of
the AgTip, we deduced that the enhancement of the multiphoton emission was caused
by the quenching of the single-exciton state due to the energy transfer from the
NQD to the AgTip and that the emission intensity was increased by enhancement of
the excitation rate due to the electric field of the LSP on the AgTip. These
results provide evidence that the photon statistics and the photon flux from the
single NQD can be manipulated by the plasmonic nanostructure through control of
the spectral overlap and the distance.
PMID- 27501389
TI - Is Transthyretin a Regulator of Ubc9 SUMOylation?
AB - Ageing and mutations of transthyretin (TTR), the thyroid hormones and retinol
transporting protein lead to amyloidosis by destabilizing the structure of TTR.
Because protein structure is regulated through posttranslational modifications,
we investigated the Small Ubiquitin-like Modifier (SUMO)ylation of TTR. We chose
the widely used Ubc9 fusion-directed SUMOylation system, which is based on a
fusion of the SUMOylation substrate of interest with Ubc9, a sole SUMO
conjugating enzyme. Surprisingly, despite our presumptions, we found that Ubc9
fused to TTR was SUMOylated at a unique set of lysine residues. Three unknown
SUMOylation sites of Ubc9-K154, K18 and K65-were revealed by mass spectrometry
(MS). The previously reported SUMOylation at K49 of Ubc9 was also observed.
SUMOylation of the lysine residues of TTR fused to Ubc9 was hardly detectable.
However, non-fused TTR was SUMOylated via trans-SUMOylation by Ubc9 fused to TTR.
Interestingly, mutating the catalytic residue of Ubc9 fused to TTR did not result
in complete loss of the SUMOylation signal, suggesting that Ubc9 linked to TTR is
directly cross-SUMOylated by the SUMO-activating enzyme E1. Ubc9, TTR or fusion
proteins composed of TTR and Ubc9 specifically affected the global SUMOylation of
cellular proteins. TTR or Ubc9 alone increased global SUMOylation, whereas
concomitant presence of TTR and Ubc9 did not further increase the amount of high
molecular weight (HMW) SUMO conjugates. Our data suggest that TTR may influence
the SUMOylation of Ubc9, thereby altering signalling pathways in the cell.
PMID- 27501390
TI - Cattle Immunized with a Recombinant Subunit Vaccine Formulation Exhibits a Trend
towards Protection against Histophilus somni Bacterial Challenge.
AB - Histophilosis, a mucosal and septicemic infection of cattle is caused by the Gram
negative pathogen Histophilus somni (H. somni). As existing vaccines against H.
somni infection have shown to be of limited efficacy, we used a reverse
vaccinology approach to identify new vaccine candidates. Three groups (B, C, D)
of cattle were immunized with subunit vaccines and a control group (group A) was
vaccinated with adjuvant alone. All four groups were challenged with H. somni.
The results demonstrate that there was no significant difference in clinical
signs, joint lesions, weight change or rectal temperature between any of the
vaccinated groups (B,C,D) vs the control group A. However, the trend to
protection was greatest for group C vaccinates. The group C vaccine was a pool of
six recombinant proteins. Serum antibody responses determined using ELISA showed
significantly higher titers for group C, with P values ranging from < 0.0148 to <
0.0002, than group A. Even though serum antibody titers in group B (5 out of 6
antigens) and group D were significantly higher compared to group A, they exerted
less of a trend towards protection. In conclusion, the vaccine used in group C
exhibits a trend towards protective immunity in cattle and would be a good
candidate for further analysis to determine which proteins were responsible for
the trend towards protection.
PMID- 27501391
TI - Assessment of Cortical Dysfunction in Patients with Intermittent Exotropia: An
fMRI Study.
AB - Neural imaging studies have found the connection between strabismus and brain
cortex. However, the pathological mechanisms of intermittent exotropia are still
not fully understood. In the present study, changes of binocular fusion related
cortices in intermittent exotropia were investigated with blood oxygen level
dependent functional magnetic resonance imaging. Activated cortices induced by
fusion stimulus were found to be distributed in several regions such as bilateral
middle occipital gyrus, bilateral middle temporal gyrus, left superior parietal
lobule and so on. Compared with normal subjects, the increased activation
intensity was observed in bilateral superior parietal lobule and inferior
parietal lobule in subjects with intermittent exotropia. These findings indicate
that binocular fusion involves a complicated brain network including several
regions. And cortical activities of bilateral superior parietal lobule and
inferior parietal lobule compensate for the binocular fusion dysfunction in
intermittent exotropia.
PMID- 27501392
TI - Microemulsions as Potential Carriers of Nisin: Effect of Composition on Structure
and Efficacy.
AB - Water-in-oil (W/O) microemulsions based on either refined olive oil (ROO) or
sunflower oil (SO), distilled monoglycerides (DMG), and ethanol were used as
nisin carriers in order to ensure its effectiveness as a biopreservative. This
work presents experimental evidence on the effects of ethanol concentration,
hydration, the nature of oil, and the addition of nisin on the nanostructure of
the proposed inverse microemulsions as revealed by electrical conductivity
measurements, dynamic light scattering (DLS), small angle X-ray scattering
(SAXS), and electron paramagnetic resonance (EPR) spectroscopy. Modeling of
representative SAXS profiles was applied to gain further insight into the effects
of ethanol and solubilized water content on the inverse swollen micelles' size
and morphology. With increasing ethanol content, the overall size of the inverse
micelles decreased, whereas hydration resulted in an increase in the micellar
size due to the penetration of water into the hydrophilic core of the inverse
swollen micelles (hydration-induced swelling behavior). The dynamic properties of
the surfactant monolayer were also affected by the nature of the used vegetable
oil, the ethanol content, and the presence of the bioactive molecule, as
evidenced by EPR spin probing experiments. According to simulation on the
experimental spectra, two populations of spin probes at different polarities were
revealed. The antimicrobial effect of the encapsulated nisin was evaluated using
the well diffusion assay (WDA) technique against Lactococccus lactis. It was
found that this encapsulated bacteriocin induced an inhibition of the
microorganism growth. The effect was more pronounced at higher ethanol
concentrations, but no significant difference was observed between the two used
vegetable oils (ROO and SO).
PMID- 27501393
TI - Regulation of Nutritional Metabolism in Transition Dairy Cows: Energy Homeostasis
and Health in Response to Post-Ruminal Choline and Methionine.
AB - This study investigated the effects of rumen-protected methionine (RPM) and rumen
protected choline (RPC) on energy balance, postpartum lactation performance,
antioxidant capacity and immune response in transition dairy cows. Forty-eight
multiparous transition cows were matched and divided into four groups: control,
15 g/d RPC, 15 g/d RPM or 15 g/d RPC + 15 g/d RPM. Diet samples were collected
daily before feeding, and blood samples were collected weekly from the jugular
vein before morning feeding from 21 days prepartum to 21 days postpartum.
Postpartum dry matter intake (DMI) was increased by both additives (P < 0.05),
and energy balance values in supplemented cows were improved after parturition (P
< 0.05). Both RPC and RPM decreased the plasma concentrations of non-esterified
fatty acids (NEFA), beta-hydroxybutyric acid (BHBA), total cholesterol (TC) and
low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but increased the plasma
levels of glucose, very-low-density lipoprotein (VLDL) and apolipoprotein B100
(ApoB 100, P < 0.05). The supplements improved milk production (P < 0.05), and
increased (P < 0.05) or tended to increase (0.05 < P < 0.10) the contents of milk
fat and protein. The post-ruminal choline and methionine elevated the blood
antioxidant status, as indicated by total antioxidant capacity (T-AOC),
glutathione peroxidase (GSH-Px) activity and the vitamin E concentration (P <
0.05), and reduced the plasma malondialdehyde (MDA) level (P < 0.05).
Furthermore, RPM and RPC elevated the plasma interleukin 2 (IL-2) concentration
and the CD4+/CD8+ T lymphocyte ratio in peripheral blood (P < 0.05).
Alternatively, the levels of tumor necrosis factor-alpha (TNF-alpha) and IL-6
were decreased by RPM and RPC (P < 0.05). Overall, the regulatory responses of
RPC and RPM were highly correlated with time and were more effective in the
postpartum cows. The results demonstrated that dietary supplementation with RPC
and RPM promoted energy balance by increasing postpartal DMI and regulating
hepatic lipid metabolism, improved postpartum lactation performance and enhanced
antioxidant capacity and immune function of transition dairy cows.
PMID- 27501394
TI - Comparison of methods using paraffin-embedded tissues and exfoliated cervical
cells to evaluate human papillomavirus genotype attribution.
AB - Monitoring the attribution of human papillomavirus (HPV) genotypes to cervical
precancerous lesions is essential in assessing the efficacy of HPV vaccines. To
resolve the lack of studies comparing the HPV genotyping procedures used to
estimate HPV genotype attribution, we undertook a retrospective cross-sectional
study to determine the appropriate genotyping procedures for evaluating the
potential efficacy of HPV vaccines. Three procedures, including two different
genotyping methods, Clinichip HPV test (C-Chip) and modified GP5+/6+ PCR coupled
to fluorescent bead sorter detection (MGP), using exfoliated cervical cells (C
Chip and C-MGP, respectively) or formalin-fixed paraffin-embedded tissues (F
MGP), were compared. The overall agreement in detecting high-risk HPV was 88.5
92.1% among the three procedures, and genotype-specific agreement was 83.9-100%
for all pairwise comparisons. In cervical intraepithelial neoplasia grade 2/3
specimens, HPV16/18 attribution estimated with the hierarchical attribution
method was consistent among the procedures: 52.3% (45/86) for C-Chip, 54.7%
(47/86) for C-MGP, and 52.3% (45/86) for F-MGP (P = 0.81).
HPV16/18/31/33/45/52/58 hierarchical attribution was 88.4% (76/86) with C-Chip,
86.0% (74/86) with C-MGP, and 83.7% (72/86) with F-MGP (P = 0.49). In cervical
intraepithelial neoplasia grade 3 specimens, the corresponding hierarchical
attribution was 96.4% (53/55) with C-Chip, 89.1% (49/55) with C-MGP, and 94.5%
(52/55) with F-MGP (P = 0.27). Although F-MGP is theoretically a reliable method
for determining HPV genotype attribution, it is acceptable to use C-Chip or C
MGP, coupled to the hierarchical attribution formula to correct the bias of
multiple infections. These approaches using exfoliated cervical cells are
practical for monitoring the efficacy of HPV vaccines.
PMID- 27501395
TI - A hybrid polyketide-nonribosomal peptide in nematodes that promotes larval
survival.
AB - Polyketides and nonribosomal peptides are two important types of natural products
that are produced by many species of bacteria and fungi but are exceedingly rare
in metazoans. Here, we elucidate the structure of a hybrid polyketide
nonribosomal peptide from Caenorhabditis elegans that is produced in the canal
associated neurons (CANs) and promotes survival during starvation-induced larval
arrest. Our results uncover a novel mechanism by which animals respond to
nutrient fluctuations to extend survival.
PMID- 27501396
TI - FRET binding antenna reports spatiotemporal dynamics of GDI-Cdc42 GTPase
interactions.
AB - Guanine-nucleotide dissociation inhibitors (GDIs) are negative regulators of Rho
family GTPases that sequester the GTPases away from the membrane. Here we ask how
GDI-Cdc42 interaction regulates localized Cdc42 activation for cell motility. The
sensitivity of cells to overexpression of Rho family pathway components led us to
a new biosensor, GDI.Cdc42 FLARE, in which Cdc42 is modified with a fluorescence
resonance energy transfer (FRET) 'binding antenna' that selectively reports Cdc42
binding to endogenous GDIs. Similar antennae could also report GDI-Rac1 and GDI
RhoA interaction. Through computational multiplexing and simultaneous imaging, we
determined the spatiotemporal dynamics of GDI-Cdc42 interaction and Cdc42
activation during cell protrusion and retraction. This revealed remarkably tight
coordination of GTPase release and activation on a time scale of 10 s, suggesting
that GDI-Cdc42 interactions are a critical component of the spatiotemporal
regulation of Cdc42 activity, and not merely a mechanism for global sequestration
of an inactivated pool of signaling molecules.
PMID- 27501398
TI - Intracerebroventricular and Intravascular Injection of Viral Particles and
Fluorescent Microbeads into the Neonatal Brain.
AB - In the study on the pathogenesis of viral encephalitis, the infection method is
critical. The first of the two main infectious routes to the brain is the
hematogenous route, which involves infection of the endothelial cells and
pericytes of the brain. The second is the intracerebroventricular (ICV) route.
Once within the central nervous system (CNS), viruses may spread to the
subarachnoid space, meninges, and choroid plexus via the cerebrospinal fluid. In
experimental models, the earliest stages of CNS viral distribution are not well
characterized, and it is unclear whether only certain cells are initially
infected. Here, we have analyzed the distribution of cytomegalovirus (CMV)
particles during the acute phase of infection, termed primary viremia, following
ICV or intravascular (IV) injection into the neonatal mouse brain. In the ICV
injection model, 5 ul of murine CMV (MCMV) or fluorescent microbeads were
injected into the lateral ventricle at the midpoint between the ear and eye using
a 10-ul syringe with a 27 G needle. In the IV injection model, a 1-ml syringe
with a 35 G needle was used. A transilluminator was used to visualize the
superficial temporal (facial) vein of the neonatal mouse. We infused 50 ul of
MCMV or fluorescent microbeads into the superficial temporal vein. Brains were
harvested at different time points post-injection. MCMV genomes were detected
using the in situ hybridization method. Fluorescent microbeads or green
fluorescent protein expressing recombinant MCMV particles were observed by
fluorescent microscopy. These techniques can be applied to many other pathogens
to investigate the pathogenesis of encephalitis.
PMID- 27501397
TI - Inhibiting androgen receptor nuclear entry in castration-resistant prostate
cancer.
AB - Clinical resistance to the second-generation antiandrogen enzalutamide in
castration-resistant prostate cancer (CRPC), despite persistent androgen receptor
(AR) activity in tumors, highlights an unmet medical need for next-generation
antagonists. We have identified and characterized tetra-aryl cyclobutanes (CBs)
as a new class of competitive AR antagonists that exhibit a unique mechanism of
action. These CBs are structurally distinct from current antiandrogens
(hydroxyflutamide, bicalutamide, and enzalutamide) and inhibit AR-mediated gene
expression, cell proliferation, and tumor growth in several models of CRPC.
Conformational profiling revealed that CBs stabilize an AR conformation
resembling an unliganded receptor. Using a variety of techniques, it was
determined that the AR-CB complex was not recruited to AR-regulated promoters
and, like apo AR, remains sequestered in the cytoplasm, bound to heat shock
proteins. Thus, we have identified third-generation AR antagonists whose unique
mechanism of action suggests that they may have therapeutic potential in CRPC.
PMID- 27501399
TI - Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation
contraction Coupling.
AB - Heart failure and cardiac arrhythmias are the leading causes of mortality and
morbidity worldwide. However, the mechanism of pathogenesis and myocardial
malfunction in the diseased heart remains to be fully clarified. Recent
compelling evidence demonstrates that changes in the myofilament Ca(2+)
sensitivity affect intracellular Ca(2+) homeostasis and ion channel activities in
cardiac myocytes, the essential mechanisms responsible for the cardiac action
potential and contraction in healthy and diseased hearts. Indeed, activities of
ion channels and transporters underlying cardiac action potentials (e.g., Na(+),
Ca(2+) and K(+) channels and the Na(+)-Ca(2+) exchanger) and intracellular Ca(2+)
handling proteins (e.g., ryanodine receptors and Ca(2+)-ATPase in sarcoplasmic
reticulum (SERCA2a) or phospholamban and its phosphorylation) are conventionally
measured to evaluate the fundamental mechanisms of cardiac excitation-contraction
(E-C) coupling. Both electrical activities in the membrane and intracellular
Ca(2+) changes are the trigger signals of E-C coupling, whereas myofilament is
the functional unit of contraction and relaxation, and myofilament Ca(2+)
sensitivity is imperative in the implementation of myofibril performance.
Nevertheless, few studies incorporate myofilament Ca(2+) sensitivity into the
functional analysis of the myocardium unless it is the focus of the study. Here,
we describe a protocol that measures sarcomere shortening/re-lengthening and the
intracellular Ca(2+) level using Fura-2 AM (ratiometric detection) and evaluate
the changes of myofilament Ca(2+) sensitivity in cardiac myocytes from rat
hearts. The main aim is to emphasize that myofilament Ca(2+) sensitivity should
be taken into consideration in E-C coupling for mechanistic analysis.
Comprehensive investigation of ion channels, ion transporters, intracellular
Ca(2+) handling, and myofilament Ca(2+) sensitivity that underlie myocyte
contractility in healthy and diseased hearts will provide valuable information
for designing more effective strategies of translational and therapeutic value.
PMID- 27501400
TI - Transgressive phenotypes and generalist pollination in the floral evolution of
Nicotiana polyploids.
AB - Polyploidy is an important driving force in angiosperm evolution, and much
research has focused on genetic, epigenetic and transcriptomic responses to
allopolyploidy. Nicotiana is an excellent system in which to study allopolyploidy
because half of the species are allotetraploids of different ages, allowing us to
examine the trajectory of floral evolution over time. Here, we study the effects
of allopolyploidy on floral morphology in Nicotiana, using corolla tube
measurements and geometric morphometrics to quantify petal shape. We show that
polyploid morphological divergence from the intermediate phenotype expected
(based on progenitor morphology) increases with time for floral limb shape and
tube length, and that most polyploids are distinct or transgressive in at least
one trait. In addition, we show that polyploids tend to evolve shorter and wider
corolla tubes, suggesting that allopolyploidy could provide an escape from
specialist pollination via reversion to more generalist pollination strategies.
PMID- 27501401
TI - Incidence and outcomes of bloodstream infections among hematopoietic cell
transplant recipients from species commonly reported to be in over-the-counter
probiotic formulations.
AB - BACKGROUND: Probiotic supplementation has been promoted for numerous health
conditions; however, safety in immunosuppressed patients is unknown. We evaluated
bloodstream infections (BSIs) caused by common probiotic organisms in
hematopoietic cell transplant recipients. METHODS: All blood culture (BC) results
from a cohort of hematopoietic cell transplant recipients transplanted at Fred
Hutchinson Cancer Research Center in Seattle, Washington, between 2002 and 2011
were reviewed. Patients with at least 1 positive BC for common probiotic
organisms (Lactobacillus species, Bifidobacterium species, Streptococcus
thermophilus, and Saccharomyces species) within 1 year post hematopoietic cell
transplantation (HCT) were considered cases. Data were collected from center
databases, which contain archived laboratory data, patient demographics, and
clinical summaries. RESULTS: A total of 19/3796 (0.5%) patients developed a BSI
from one of these organisms within 1 year post HCT; no Bifidobacterium species or
S. thermophilus were identified. Cases had a median age of 49 years
(interquartile range [IQR]: 39-53), and the majority were allogeneic
hematopoietic cell transplant recipients (14/19, 74%). Most positive BCs were
Lactobacillus species (18/19) and occurred at a median of 84 days (IQR: 34-127)
post transplant. The incidence rate of Lactobacillus bacteremia was 1.62 cases
per 100,000 patient-days; the highest rate occurred within 100 days post
transplant (3.3 per 100,000 patient-days). Eight patients (44%) were diagnosed
with acute graft-versus-host disease of the gut prior to the development of
bacteremia. No mortality was attributable to any of these infections. CONCLUSION:
Organisms frequently incorporated in available over-the-counter probiotics are
infrequent causes of bacteremia after HCT. Studies evaluating the use of
probiotics among high-risk patients are needed.
PMID- 27501402
TI - A possible interaction between periostin and CD163+ skin-resident macrophages in
pemphigus vulgaris and bullous pemphigoid.
AB - Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are autoimmune blistering
diseases, and substantial numbers of CD163+ tissue-associated macrophages (TAMs)
are detected in both diseases. PV and BP possess different subsets of helper T
cells, suggesting that the cytokine profiles of PV and BP might be different. The
purpose of this study was to investigate the microenvironment of lesional skin
and serum of PV and BP patients, focusing on the immunomodulatory factors related
to TAMs, such as periostin (POSTN), chemokines, cytokines and matrix
metalloproteinases (MMPs). We first performed immunohistological staining of
POSTN in PV and BP lesions. POSTN was prominent in the superficial dermis in both
PV and BP lesions. Next, to validate the activation of CD163+ TAMs in PV and BP
patients, we examined the serum levels of soluble (s)CD163. The serum sCD163
levels in PV and BP patients are significantly higher than in healthy controls.
To further elucidate the molecular mechanisms of the effects of POSTN on CD163+
TAMs in PV and BP, we examined chemokines, MMPs and cytokines selected by DNA
microarray database. The serum CXCL5 levels from PV patients are significantly
higher than those in BP patients and healthy controls. The IL-36gamma expression
on infiltrating macrophages was prominent only in the lesional skin of PV, while
the MMP12 deposition was detected in both PV and BP lesions. Our results shed
light on the novel pathogenesis of PV through CD163+ TAMs.
PMID- 27501403
TI - Mitral valve repair for moderate ischemic mitral regurgitation.
PMID- 27501404
TI - Use of computer-aided holographic models improves performance in a cadaver
dissection-based course in gross anatomy.
AB - A compelling, innovative approach to teaching gross anatomy is the use of
computer-aided holographic models. They allow for clean, time-saving dissection,
manipulation of structures and appreciation of anatomical relationships, and
potential elimination of the need for cadavers. The present study tests the
hypothesis that using holographic models improves mastery of anatomical
information. First-year medical students were taught gross anatomy using the
dissection of donor cadavers, manipulation of digitized 3-dimensional holographic
renderings, and examination of plastinated specimens. The effectiveness of these
approaches was assessed by comparing students' performance on identification
questions on cadavers (qC), holographic models (qH), and plastinated specimens
(qP). Students in the top quintile of the class performed strongly on qC, qH, and
qP. In contrast, performance by students in the bottom quintile was uneven; they
scored best on qH. Performance on the qP was relatively non-discriminating.
Students in the top quintile scored higher on the biological sciences section of
the Medical College Admission Test (MCAT) than students in the lowest quintile,
whereas students in the lowest quintile had higher scores on the verbal section
of their MCATs. The availability of different approaches for presenting gross
anatomy improves the success of students in mastering the material, particularly
for students struggling with the information. The use of holographic models
apparently reaches students who may be challenged to learn the material using
traditional approaches. This may be linked to potentially predictive information
gleaned through performance on the MCAT. Clin. Anat. 29:917-924, 2016. (c) 2016
Wiley Periodicals, Inc.
PMID- 27501405
TI - Complex vein graft intervention after double-valve transcatheter aortic valve
replacement.
PMID- 27501406
TI - Evolution of nonculprit coronary atherosclerotic plaques assessed by serial
virtual histology intravascular ultrasound in patients with ST-segment elevation
myocardial infarction and chronic total occlusion.
AB - OBJECTIVE: The pathophysiology and natural course of coronary nonculprit plaques
remain unclear. We investigated whether the short-term natural course of
nonculprit plaques differs between ST-segment elevation myocardial infarction
(STEMI) and chronic total occlusion (CTO) patients. METHODS: We performed serial
virtual histology intravascular ultrasound on nonculprit plaques in 26 STEMI and
11 CTO lesions at baseline and the 6-month follow-up. RESULTS: At baseline, more
lesions in the STEMI group were virtual histology intravascular ultrasound
derived thin-cap fibroatheromas (TCFA; 76.9 vs. 18.1%, P=0.002). During the
follow-up period, the plaque composition changed dynamically in the STEMI group
(fibrofatty: 9.8+/-1.9 to 17.3+/-2.9%, P=0.030; dense calcium: 12.7+/-1.8 to
8.1+/-1.7%, P=0.026; necrotic core: 21.1+/-1.8 to 15.4+/-2.2%, P=0.052), with a
consistent plaque size. In the CTO group, the plaque composition and plaque size
remained consistent without a significant change. Also, more lesions in the STEMI
group remained as or progressed to TCFA, compared with the CTO group (67 vs. 11%,
P=0.089). Factors associated with a persistent TCFA or with a new development of
TCFA were a large necrotic core volume index and the diagnosis of STEMI, whereas
new statin usage was a protective factor. CONCLUSION: Nonculprit lesions in STEMI
patients were more unstable at the baseline compared with those in CTO patients.
During follow-up, nonculprit lesions in STEMI and CTO patients showed a distinct
pattern of change; the former were stabilized in plaque composition, whereas the
latter remained consistent. The diagnosis of STEMI and a large necrotic core
volume were predictors of evolution to a TCFA, and new statin usage was a
protective factor.
PMID- 27501407
TI - Experimental Investigation of Secondary Flow Structures Downstream of a Model
Type IV Stent Failure in a 180 degrees Curved Artery Test Section.
AB - The arterial network in the human vasculature comprises of ubiquitously present
blood vessels with complex geometries (branches, curvatures and tortuosity).
Secondary flow structures are vortical flow patterns that occur in curved
arteries due to the combined action of centrifugal forces, adverse pressure
gradients and inflow characteristics. Such flow morphologies are greatly affected
by pulsatility and multiple harmonics of physiological inflow conditions and vary
greatly in size-strength-shape characteristics compared to non-physiological
(steady and oscillatory) flows (1 - 7). Secondary flow structures may ultimately
influence the wall shear stress and exposure time of blood-borne particles toward
progression of atherosclerosis, restenosis, sensitization of platelets and
thrombosis (4 - 6, 8 - 13). Therefore, the ability to detect and characterize
these structures under laboratory-controlled conditions is precursor to further
clinical investigations. A common surgical treatment to atherosclerosis is stent
implantation, to open up stenosed arteries for unobstructed blood flow. But the
concomitant flow perturbations due to stent installations result in multi-scale
secondary flow morphologies (4 - 6). Progressively higher order complexities such
as asymmetry and loss in coherence can be induced by ensuing stent failures vis-a
vis those under unperturbed flows (5). These stent failures have been classified
as "Types I-to-IV" based on failure considerations and clinical severity (14).
This study presents a protocol for the experimental investigation of the complex
secondary flow structures due to complete transverse stent fracture and linear
displacement of fractured parts ("Type IV") in a curved artery model. The
experimental method involves the implementation of particle image velocimetry (2C
2D PIV) techniques with an archetypal carotid artery inflow waveform, a
refractive index matched blood-analog working fluid for phase-averaged
measurements (15 - 18). Quantitative identification of secondary flow structures
was achieved using concepts of flow physics, critical point theory and a novel
wavelet transform algorithm applied to experimental PIV data (5, 6, 19 - 26).
PMID- 27501408
TI - Double Gene Targeting Multiplex Polymerase Chain Reaction-Restriction Fragment
Length Polymorphism Assay Discriminates Beef, Buffalo, and Pork Substitution in
Frankfurter Products.
AB - Beef, buffalo, and pork adulteration in the food chain is an emerging and
sensitive issue. Current molecular techniques to authenticate these species
depend on polymerase chain reaction (PCR) assays involving long and single
targets which break down under natural decomposition and/or processing
treatments. This novel multiplex polymerase chain reaction-restriction fragment
length polymorphism assay targeted two different gene sites for each of the
bovine, buffalo, and porcine materials. This authentication ensured better
security, first through a complementation approach because it is highly unlikely
that both sites will be missing under compromised states, and second through
molecular fingerprints. Mitochondrial cytochrome b and ND5 genes were targeted,
and all targets (73, 90, 106, 120, 138, and 146 bp) were stable under extreme
boiling and autoclaving treatments. Target specificity and authenticity were
ensured through cross-amplification reaction and restriction digestion of PCR
products with AluI, EciI, FatI, and CviKI-1 enzymes. A survey of Malaysian
frankfurter products revealed rampant substitution of beef with buffalo but
purity in porcine materials.
PMID- 27501409
TI - Simulator evaluation of a prototype device to reduce medication errors in
anaesthesia.
AB - We undertook a randomised control led trial to evaluate the effect of a prototype
device which attaches to the intravenous drug administration port, and allows
injection of intravenous drugs only after the user scans the barcode on the
syringe label. This requires two steps: first, that the correct drug label is
generated; and second, that the syringe-with-label is scanned before
administration. Ten anaesthetists, who were unaware of the primary outcome being
measured, administered general anaesthesia for two simulated standardised cases
each without and with our prototype (control and intervention, respectively). The
primary outcome measured was compliance with a safe drug administration procedure
(defined as a two-step procedure where, step one is scanning a drug ampoule to
print a label for a syringe and step two is scanning of the labelled syringe
before administering it intravenously). A total of 182 intravenous drug
administrations occurred in the study (91 in each group). We found that the use
of our prototype increased safe drug administration behaviour in experienced
anaesthetists; 33 (36.3% [95% CI 26-47%]) vs. 91 (100% [95% CI 96-100%]) in the
control and intervention groups, respectively (p = 0.0001).
PMID- 27501410
TI - Development of an adverse events reporting form for Korean folk medicine.
AB - PURPOSE: We developed an adverse events (AEs) reporting form for Korean folk
medicine. METHODS: The first version of the form was developed and tested in the
clinical setting for spontaneous reporting of AEs. Additional revisions to the
reporting form were made based on collected data and expert input. RESULTS: We
developed an AEs reporting form for Korean folk medicine. The items of this form
were based on patient information, folk medicine properties, and AEs. For
causality assessment, folk medicine properties such as classification, common and
vernacular names, scientific name, part used, harvesting time, storage
conditions, purchasing route, product licensing, prescription, persons with
similar exposure, any remnant of raw natural products collected from the patient,
and cautions or contraindications were added. CONCLUSIONS: This is the first
reporting form for AEs that incorporates important characteristics of Korean folk
medicine. This form would have an important role in reporting adverse events for
Korean folk medicine. (c) 2016 The Authors. Pharmacoepidemiology and Drug Safety
Published by John Wiley & Sons Ltd.
PMID- 27501411
TI - Capillary electrophoresis in a fused-silica capillary with surface roughness
gradient.
AB - The electro-osmotic flow, a significant factor in capillary electrophoretic
separations, is very sensitive to small changes in structure and surface
roughness of the inner surface of fused silica capillary. Besides a number of
negative effects, the electro-osmotic flow can also have a positive effect on the
separation. An example could be fused silica capillaries with homogenous surface
roughness along their entire separation length as produced by etching with
supercritical water. Different strains of methicillin-resistant and methicillin
susceptible Staphylococcus aureus were separated on that type of capillaries. In
the present study, fused-silica capillaries with a gradient of surface roughness
were prepared and their basic behavior was studied in capillary zone
electrophoresis with UV-visible detection. First the influence of the electro
osmotic flow on the peak shape of a marker of electro-osmotic flow, thiourea, has
been discussed. An antifungal agent, hydrophobic amphotericin B, and a protein
marker, albumin, have been used as model analytes. A significant narrowing of the
detected zones of the examined analytes was achieved in supercritical-water
treated capillaries as compared to the electrophoretic separation in smooth
capillaries. Minimum detectable amounts of 5 ng/mL amphotericin B and 5 MUg/mL
albumin were reached with this method.
PMID- 27501412
TI - Towards a systems-level understanding of development in the marine annelid
Platynereis dumerilii.
AB - Platynereis dumerilii is a segmented marine worm from the phylum Annelida, a
member of the Lophotrochozoans. Platynereis is easily maintained in the lab and
exhibits a highly stereotypic development through spiral cleavage with a small,
transparent, free-swimming larva highly suitable for microscopy studies. A
protocol for embryo microinjection in Platynereis has enabled several genetic
tools to be developed, paving the way for functional studies. Recent Platynereis
studies have provided insights into the function of several signaling pathways in
development. Platynereis has also proven a useful model system for comparative
evolutionary developmental studies, allowing the formation of new hypotheses on
the evolution of neuroendocrine signaling, body patterning, and organ
development. Combining existing large datasets of spatial gene expression
mapping, cell lineage mapping, and neuronal circuits with functional analyses of
developmental genes represents a promising approach for future studies aiming at
a systems-level understanding of development in Platynereis.
PMID- 27501413
TI - miR-346 promotes migration and invasion of nasopharyngeal carcinoma cells via
targeting BRMS1.
AB - The aim of this study is to determine the expression and roles of miR-346 in
nasopharyngeal carcinoma (NPC). We showed that miR-346 was upregulated in NPC
tissues compared with adjacent non-tumorous nasopharyngeal tissues. Inhibition of
miR-346 significantly attenuated the migration and invasion of NPC cells.
Luciferase reporter assay showed that miR-346 targeted the 3'-untranslated region
(3'-UTR) of breast cancer metastasis suppressor 1 (BRMS1). Overexpression of miR
346 suppressed the endogenous expression of BRMS1 in NPC cells. There was a
significant negative correlation between miR-346 and BRMS1 protein expression in
NPC tissues (r = -0.372, P = 0.008). Rescue experiments demonstrated that
overexpression of BRMS1 lacking the 3'-UTR impaired the invasiveness of NPC cells
transfected with miR-346 mimic. Taken together, miR-346 shows the ability to
promote the migration and invasion of nasopharyngeal cancer cells via targeting
BRMS1 and represents a potential therapeutic target for NPC.
PMID- 27501414
TI - SNPing SCNA regulatory elements gives a CRISPR view of genetic susceptibility in
Parkinson's disease.
PMID- 27501415
TI - Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like
Conjugates Containing C(5) Triazole Arm.
AB - Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6
16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings
indicated the structure of novel derivatives in solution and demonstrated that
the rebuilt C(5) arm is slightly differently oriented relative to the aglycone
part if compared to that of spiramycin (1). Combined analysis of biological data
together with experimentally determined lipophilicity (clogP) and solubility show
the importance of the chemical nature of the newly introduced triazole C(5) arm
in the presence of attractive antibacterial and anticancer potency. The most
cytotoxic active triazole conjugates having a hydrophobic and bulky C(5) arm
showed higher selectivity toward cancer cell lines (HeLa, KB, MCF-7, Hep-G2, and
U87) relative to HDF normal cells than that of the parent spiramycin. Our studies
have demonstrated that the aldehyde group is not crucial for the presence of
interesting antibacterial [MIC(S. pneumoniae) ~ 1.2 MUM] and anticancer
[IC50(HepG2) ~ 6 MUM] properties of 16-membered lactone macrolides based on
spiramycin's aglycone.
PMID- 27501417
TI - Structural design approaches for creating fat droplet and starch granule
mimetics.
AB - This article focuses on hydrogel-based strategies for creating reduced calorie
foods with desirable physicochemical, sensory, and nutritional properties.
Initially, the role of fat droplets and starch granules in foods is discussed,
and then different methods for fabricating hydrogel beads are reviewed, including
phase separation, antisolvent precipitation, injection, and emulsion template
methods. Finally, the potential application of hydrogel beads as fat droplet and
starch granule replacements is discussed. There is still a need for large-scale,
high-throughout, and economical methods of fabricating hydrogel beads suitable
for utilization within the food industry.
PMID- 27501416
TI - Genome-wide analysis suggests divergent evolution of lipid
phosphotases/phosphotransferase genes in plants.
AB - Genes of the LPPT (lipid phosphatase/phosphotransferase) family play important
roles in lipid phosphorous transfer and triacylglycerol accumulation in plants.
To provide overviews of the plant LPPT family and their overall relationships,
here we carried out genome-wide identifications and analyses of plant LPPT family
members. A total of 643 putative LPPT genes were identified from 48 sequenced
plant genomes, among which 205 genes from 14 plants were chosen for further
analyses. Plant LPPT genes belonged to three distinctive groups, namely the LPT
(lipid phosphotransfease), LPP (lipid phosphatase), and pLPP (plastidic lipid
phosphotransfease) groups. Genes of the LPT group could be further partitioned
into three groups, two of which were only identified in terrestrial plants. Genes
in the LPP and pLPP groups experienced duplications in early stages of plant
evolution. Among 17 Zea mays LPPT genes, divergence of temporal-spatial
expression patterns was revealed based on microarray data analysis. Peptide
sequences of plant LPPT genes harbored different conserved motifs. A test of
Branch Model versus One-ratio Model did not support significant selective
pressures acting on different groups of LPPT genes, although quite different
nonsynonymous evolutionary rates and selective pressures were observed. The
complete picture of the plant LPPT family provided here should facilitate further
investigations of plant LPPT genes and offer a better understanding of lipid
biosynthesis in plants.
PMID- 27501418
TI - Division of Responsibility.
PMID- 27501419
TI - Determination of pholcodine in syrups and human plasma using the
chemiluminescence system of tris(1,10 phenanthroline)ruthenium(II) and acidic
Ce(IV).
AB - Pholcodine is an opiate derivative drug which is widely used in pediatric
medicine. In this study, a chemiluminescence (CL) method is described that
determines pholcodine in human plasma and syrup samples. This method is based on
the fact that pholcodine can greatly enhance the weak CL emission of reaction
between tris(1,10 phenanthroline)ruthenium(II), Ru(phen)32+ , and acidic Ce(IV).
The CL mechanism is described in detail using UV-vis light, fluorescence and CL
spectra. Effects of chemical variables were investigated and under optimum
conditions, CL intensity was proportional to the pholcodine concentration over
the range 4.0 * 10-8 to 8.0 * 10-6 mol L-1 . The limit of detection (LOD) (S/N
= 3) was 2.5 * 10-8 mol L-1 . Percent of relative standard deviations (%RSD)
for 3.0 * 10-7 and 3.0 * 10-6 mol L-1 of pholcodine was 2.9 and 4.0%,
respectively. Effects of common ingredients were investigated and the method was
applied successfully to the determination of pholcodine in syrup samples and
human plasma.
PMID- 27501420
TI - Hyperglycemia in septic patients: an essential stress survival response in all, a
robust marker for risk stratification in some, to be messed with in none.
PMID- 27501422
TI - A SWAT model validation of nested-scale contemporaneous stream flow, suspended
sediment and nutrients from a multiple-land-use watershed of the central USA.
AB - There is an ongoing need to validate the accuracy of predictive model simulated
pollutant yields, particularly from multiple-land-use (i.e. forested,
agricultural, and urban) watersheds. However, there are seldom sufficient
observed data sets available that supply requisite spatial and temporal
resolution and coupled multi-parameter constituents for rigorous model
performance assessment. Four years of hydroclimate and water quality data were
used to validate SWAT model estimates of monthly stream flow, suspended sediment,
total phosphorus, nitrate, nitrite, ammonium, and total inorganic nitrogen from 5
nested-scale gauging sites located in a multiple-land-use watershed of the
central USA. The uncalibrated SWAT model satisfactorily simulated monthly stream
flow with Nash-Sutcliffe efficiency (NSE) values ranging from 0.50 near the
headwaters, to 0.75 near the watershed outlet. However, the uncalibrated model
did not accurately simulate monthly sediment, total phosphorus, nitrate, nitrite,
ammonium, and total inorganic nitrogen with NSE values<0.05. Calibrating the SWAT
model to multiple gauging sites within the watershed improved estimates of
monthly stream flow (NSE=0.83), sediment (NSE=0.78), total phosphorus (NSE=0.81),
nitrate (NSE=0.90), and total inorganic nitrogen (NSE=0.86). However, NSE values
were <-0.16 for nitrite and ammonium estimates. Additionally, model performance
decreased for sediment, nitrate, and total inorganic nitrogen during the
validation period with NSE values<0.62, 0.52, and 0.36, respectively. Results
highlight the benefits of calibrating the SWAT model to multiple gauging sites
and provide guidance to SWAT model (or similar models) users wishing to improve
model performance at multiple scales.
PMID- 27501421
TI - Moss and lichen biomonitoring of atmospheric mercury: A review.
AB - Long-range transport and residence time of elemental Hg (Hg degrees ) in air
promote global dispersion and deposition in remote ecosystems. Many biotic and
abiotic factors contribute to the photoreduction and phytovolatilization of Hg
from terrestrial ecosystems, and the assessment of deposition and volatilization
fluxes is very challenging. Mosses and lichens are widespread in nature and
constitute the dominant vegetation in alpine and polar ecosystems. This review
surveys the results of Hg biomonitoring with cryptogams in areas with different
Hg sources and deposition processes. Lichen and moss ecophysiology, and factors
affecting Hg uptake and bioaccumulation are discussed. Although some laboratory
experiments indicate a linear accumulation of Hg in cryptogams exposed to Hg
degrees , without any significant release, in nature the Hg accumulated in
cryptogams is in a dynamic equilibrium with Hg in air and decreases when
organisms are transplanted to clean environments. Mercury concentrations in
mosses and lichens have often been used to estimate concentrations and deposition
fluxes of atmospheric Hg; however, Hg degrees exchanges between cryptogams and
air, and the time necessary for mosses and lichens to equilibrate elemental
composition with changing atmospheric chemistry, preclude reliable estimates.
Biological processes of Hg uptake and exchange with air cannot be reproduced by
mechanical collectors, and comparisons between Hg concentrations in biomonitors
and those in atmospheric deposition are scarcely reliable. However, the Hg
biomonitoring with mosses and lichens is easy and cheap and allows to locate "hot
spots" of natural or anthropogenic emissions and to assess spatio-temporal
changes in Hg deposition patterns. Climate change is affecting the global Hg
cycle through the melting of sea-ice in coastal Polar Regions, and modifying Hg
sequestration in mountain ecosystems. Despite limitations, large-scale monitoring
of Hg with mosses and lichens may be used as a tool to evaluate the impact of
global processes in remote ecosystems.
PMID- 27501423
TI - Removal of trace level amounts of twelve sulfonamides from drinking water by UV
activated peroxymonosulfate.
AB - Trace levels of residual antibiotics in drinking water may threaten public health
and become a serious problem in modern society. In this work, we investigated the
degradation of twelve sulfonamides (SAs) at environmentally relevant trace level
concentrations by three different methods: ultraviolet (UV) photolysis,
peroxymonosulfate (PMS) oxidation, and UV-activated PMS (UV/PMS). Sulfaguanidine,
sulfadiazine, sulfamerazine, sulfamethazine, sulfathiazole, sulfamethoxydiazine,
and sulfadimethoxine were be effectively removed by direct UV photolysis and PMS
oxidation. However, sulfanilamide, sulfamethizole, sulfamethoxazole,
sulfisoxazole, and sulfachloropyridazine were not completely degraded, despite
prolonging the UV irradiation time to 30min or increasing the PMS concentration
to 5.0mg.L-1. UV/PMS provided more thorough elimination of SAs, as demonstrated
by the complete removal of 200ng.L-1 of all SAs within 5min at an initial PMS
concentration of 1.0mg.L-1. UV/PMS promoted SA decomposition more efficiently
than UV photolysis or PMS oxidation alone. Bicarbonate concentration and pH had a
negligible effect on SA degradation by UV/PMS. However, humic acid retarded the
process. Removal of 200ng.L-1 of each SA from a sample of sand-filtered effluent
from a drinking water treatment plant (DWTPs) was quickly and completely achieved
by UV/PMS. Meanwhile, about 41% of the total organic carbon (TOC) was eliminated.
Scavenging experiments showed that sulfate radical (SO4-) was the predominant
species involved in the degradation. It is concluded that UV/PMS is a rapid and
efficient method for removing trace-level SAs from drinking water.
PMID- 27501424
TI - Effects of biocide treatments on the biofilm community in Domitilla's catacombs
in Rome.
AB - Different types of biofilms are widespread on lithic faces of the Catacombs of
Domitilla (Rome, Italy) due to the favorable microclimatic conditions
(temperature, high RH% and low irradiance). The biofilm, once established,
becomes particularly dangerous due to the coverage of valuable surfaces causing
spoilage, softening of materials and mineral precipitation. It is common practice
to treat these surfaces with biocides in order to eradicate the microorganisms
present. The aim of the present research was to compare the changes occurring to
the microbial community present in the biofilm in one site of the Catacombs of
Domitilla (CD15) before and after a biocide treatment (a mixture of quaternary
ammonium compounds and octylisothiazolone, OIT), applied for a one month period.
A multistep approach was followed, based on microscopy, cultural methods and
molecular techniques (f-ITS and 16S rDNA sequencing), for the phenotypic and
genetic analysis of the culturable microbial population. Our results highlighted
that the biocide treatments had little effect against cyanobacteria, while the
bacterial population increased in numbers but changed drastically in terms of
diversity. In fact, some bacteria proliferate at the expense of the organic
matter released by dead microorganisms as demonstrated by laboratory tests.
Further, our data describe how the microbial interaction can have different
responses depending on the favorable conditions for one kind of microorganism in
respect to the others. This study exemplifies the real risks of applying biocide
treatments on complex microbial communities and pinpoints the necessity of
subjecting treatments to monitoring and reassessment. Moreover, the work showed
the potential of bacteria isolated after the treatment for use, under controlled
conditions, in combatting unwanted microbial growth in that they possess a
positive tropism toward stressed microorganisms and high hydrolytic enzymatic
activity against cell components (e.g. cellulose, chitin and pectin). A tentative
protocol is proposed.
PMID- 27501425
TI - Multi-matrix quantification and risk assessment of pesticides in the longest
river of the Iberian peninsula.
AB - The distribution of pesticides in dissolved aqueous phase (DAP), suspended
particulate matter (SPM) and Scrobicularia plana soft tissues from the Tagus
River estuary was determined to evaluate the chemicals pollution status and their
hazard potential in this area. Samples were collected in 6 campaigns (December
2012-October 2013), from 3 strategical sites, and analysed via different
extraction procedures followed by gas chromatography tandem mass spectrometry (GC
MS/MS) determination. The contamination profile among matrices (DAP, SPM, and
soft tissue from bivalves (STB)) was marked by average concentrations of 345ng/L,
0.51mg/kg, and 0.02mg/kg, respectively, with several samples above the 2013/39/EU
Directive of environmental quality standards (EQS); no differences were observed
between sex. A wider range of pesticides was present in STB (n=53) than in SPM
(n=36) and DAP (n=19) matrices. Sediment-water partition coefficient,
bioaccumulation factor in both DAP and SPM fraction were estimated ranging
between 2.5 and 4.4 and 0.008-2799, respectively. The spatial distribution of
most pesticides and physicochemical parameters were consistent, indicating a
pollution pattern primarily near the Trancao River mouth. Due to the presence of
the target compounds, calculated risk quotients pointed out potential hazards for
aquatic organisms, mainly to invertebrates. The estimated average daily intake,
theoretical maximum daily intake, and hazard quotient of the studied pesticides
via bivalve ingestion-indicated no risk for human health, although it is
important to note possible biomagnification processes that may happen along the
estuarine food-chain.
PMID- 27501426
TI - Biodegradation and detoxification of naphthenic acids in oil sands process
affected waters.
AB - After oil sands process affected water (OSPW) was treated in a continuous flow
biofilm reactor, about 40% of the organic compounds in the acid extractable
fraction (AEF) including naphthenic acids (NAs) were degraded resulting in a
reduction of 73% in the Microtox acute toxicity and of 22% in the yeast
estrogenic assay. Using effect directed analysis, treated and untreated OSPW were
fractionated by solid phase extraction and the fractions with the largest
decrease in toxicity and estrogenicity were selected for analysis by electrospray
ionization combined with linear ion trap and a high-resolution Orbitrap mass
spectrometer (negative ion mode). The aim of this study was to determine whether
compositional changes between the untreated and treated fractions provide insight
related to biodegradation and detoxification of NAs. The O2S, O3S and O4S
compounds were either not major contributors of toxicity or estrogenicity or the
more toxic or estrogenic ones were biodegraded. The O3- and O4-NAs seem to be
more readily metabolized than O2NAs and their degradation would contribute to
detoxification. The decrease in acute toxicity may be associated with the
degradation of C12 and C13 bicyclic and C12-C14 tricyclic NAs while the decrease
in estrogenicity may be linked to the degradation of C16 O2-NAs with double bond
equivalents (DBE)=5 and 6, C16 and 17 O2-NAs with DBE=7, and C19-O2-NAs with
DBE=8. The residual acute toxicity may be caused by recalcitrant components
and/or degradation products such as the O2 bicyclic and tricyclic NAs,
particularly the C14 and C15 bicyclic and C14-C16 tricyclic NAs as well as the
polycyclic aromatic NAs (DBE>=5 compounds). The decrease in estrogenicity may be
linked to the degradation of the O3 and O4 oxidized NAs while much of the
residual estrogenicity may be due to the recalcitrant polycyclic aromatic O2-NAs.
Hence, treatment to further detoxify OSPW should target these compounds.
PMID- 27501427
TI - The phosphorus release pathways and their mechanisms driven by organic carbon and
nitrogen in sediments of eutrophic shallow lakes.
AB - To reveal phosphorus (P) release pathways from sediment and their mechanisms
induced by organic matter enrichment, 116 sampling sites (including surface water
and sediment) in 29 shallow lakes with different eutrophic degrees in Wuhan city,
China, were investigated from July 2011 to November 2011. Empirical relationship
and structural equation model indicated that the decomposition of total organic
matter (TOM), including proteins (PRT), carbo-hydrates (CHO) and lipids
(especially PRT) mediated by extracellular enzymes, accelerated the formation of
anaerobic status. On the other hand, coupled nitrification-denitrification caused
by ammonium (NH4+-N) accumulation due to PRT decomposition further aggravated
anaerobic status and nitrate removal in terms of the increase of dehydrogenase
activity (DHA). As a consequence, ferric iron was reduced to ferrous iron and
soluble reactive phosphorus (SRP) was released from iron-bound phosphorus
(Fe(OOH)~P) in sediments. In addition, extracellular alkaline phosphatase can be
induced by organic carbon and nitrogen on condition that the input of nitrogen
(N) and carbon (C) exceeded by far that of P. Taken together, enrichment of N and
C can result in P release through the formation of anaerobic status and alkaline
phosphatase production. Hence, we indicated that a close coupling existed among
C, N and P cycles.
PMID- 27501428
TI - Measurement of rare isotopologues of nitrous oxide by high-resolution multi
collector mass spectrometry.
AB - RATIONALE: Bulk and position-specific stable isotope characterization of nitrous
oxide represents one of the most powerful tools for identifying its environmental
sources and sinks. Constraining (14) N(15) N(18) O and (15) N(14) N(18) O will
add two new dimensions to our ability to uniquely fingerprint N2 O sources.
METHODS: We describe a technique to measure six singly and doubly substituted
isotopic variants of N2 O, constraining the values of delta(15) N, delta(18) O,
?(17) O, (15) N site preference, and the clumped isotopomers (14) N(15) N(18) O
and (15) N(14) N(18) O. The technique uses a Thermo MAT 253 Ultra, a high
resolution multi-collector gas source isotope ratio mass spectrometer. It
requires 8-10 hours per sample and ~10 micromoles or more of pure N2 O. RESULTS:
We demonstrate the precision and accuracy of these measurements by analyzing N2 O
brought to equilibrium in its position-specific and clumped isotopic composition
by heating in the presence of a catalyst. Finally, an illustrative analysis of
biogenic N2 O from a denitrifying bacterium suggests that its clumped isotopic
composition is controlled by kinetic isotope effects in N2 O production.
CONCLUSIONS: We developed a method for measuring six isotopic variants of N2 O
and tested it with analyses of biogenic N2 O. The added isotopic constraints
provided by these measurements will enhance our ability to apportion N2 O
sources.
PMID- 27501429
TI - Compound-specific bromine isotope ratio analysis using gas
chromatography/quadrupole mass spectrometry.
AB - RATIONALE: Brominated organic compounds (BOCs) are common persistent toxic
pollutants. Compound-specific stable bromine isotope ratio analysis is one of the
potential approaches for investigating BOC transformations in the environment. In
the present study, we demonstrate that precise bromine isotope analysis of BOCs
can be successfully performed by gas chromatography/quadrupole mass spectrometry
(GC/qMS) systems that are widely available in analytical laboratories. METHODS:
Optimization and validation of the GC/qMS method were performed by analysis of
bromoform, 3-bromophenol and 4-bromotoluene. In addition, comparison of the
results obtained by GC/qMS and GC/multi-collector inductively coupled plasma mass
spectrometry (MC-ICPMS) for 1,2-dibromoethane and 3-bromophenol samples with
different bromine isotope composition was carried out to evaluate the analytical
performance of the developed method. RESULTS: Precisions in the range 0.2-0.30/00
were attained for sample amounts in the range of tens to thousands pmol. Good
correlation between the results obtained by GC/qMS and GC/MC-ICPMS for laboratory
standard materials (1,2-dibromoethane and 3-bromophenol) (regression coefficient
R(2) > 0.98) was achieved. CONCLUSIONS: The GC/qMS method for bromine isotope
analysis shows a good performance and can be applied routinely for studying
transformations of BOCs. Due to the observed dependence of the measured isotope
ratios on the amount of the analyte and the calculation scheme applied,
normalization of the results versus appropriate standards is required for source
attribution applications. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501431
TI - Red deer bone and antler collagen are not isotopically equivalent in carbon and
nitrogen.
AB - RATIONALE: Bone and antler collagen delta(13) C and delta(15) N values are often
assumed to be equivalent when measured in palaeodietary, palaeoclimate and
palaeocological studies. Although compositionally similar, bone grows slowly and
is remodelled whereas antler growth is rapid and remodelling does not occur.
These different patterns of growth could result in isotopic difference within
antler and between the two tissue types. Here we test whether red deer (Cervus
elaphus) bone and antler delta(13) C and delta(15) N values are equivalent, and
whether intra-antler isotopic values are uniform. METHODS: Bone and antler were
isotopically analysed from six stags that lived in a temperate maritime climate
on the Isle of Rum, Scotland. Multiple antlers from different years were sampled
per individual, together with a single bone sample per individual. Up to 12
samples were taken along the length of each antler (total of 25 antlers, 259
samples) so that a chronological record of the isotopic composition during antler
growth could be obtained. Collagen was extracted and its delta(13) C and
delta(15) N values were measured by continuous-flow isotope ratio mass
spectrometry. RESULTS: Intra-antler collagen isotope signatures vary, and show
that not all antlers from an individual or a growth year are equivalent in carbon
and nitrogen isotopic ratios. delta(15) N values typically increase with distance
along antler length, but no overall trend is observed in delta(13) C values. An
isotopic offset is visible between bone and antler, with bone delta(13) C and
delta(15) N values being higher in most cases. CONCLUSIONS: Bone and antler
collagen delta(13) C and delta(15) N values are not isotopically equivalent and
are therefore not directly comparable in palaeodietary, palaeoclimate and
palaeocological studies. Bone and antler collagen isotopic differences probably
relate to differential metabolic processes during the formation of the two
tissues. Intra- and inter-antler isotopic variations probably reflect the
isotopic composition of an individual's diet rather than physiological
parameters, and may have the potential to provide high-resolution individual
specific information in modern and ancient cervid populations. Copyright (c) 2016
John Wiley & Sons, Ltd.
PMID- 27501430
TI - Measurement of the accurate mass of a 50 MDa infectious virus.
AB - RATIONALE: Bacteriophage P22 is believed to contain a total of 521 copies of 9
different proteins and a 41,724 base pair genome. Despite its enormous size and
complexity, phage P22 can be electrosprayed, and it remains intact in ultra-high
vacuum where its molar mass distribution has been measured. METHODS: Phage P22
virions were generated by complementation in Salmonella enterica and purified.
They were transferred into 100 mM ammonium acetate and then electrosprayed. The
masses of individual virions were determined using charge detection mass
spectrometry. RESULTS: The stoichiometry of the protein components of phage P22
is sufficiently well known that the theoretical molar mass can be determined to
within a narrow range. The measured average molar mass of phage P22, 52,180 +/-
59 kDa, is consistent with the theoretical molar mass and supports the proposed
stoichiometry of the components. The intrinsic width of the phage P22 mass
distribution can be accounted for by the distribution of DNA packaged by the
headful mechanism. CONCLUSIONS: At over 50 MDa, phage P22 is the largest object
with a well-defined molar mass to be analyzed by mass spectrometry. The narrow
measured mass distribution indicates that the virions survive the transition into
the gas phase intact. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27501432
TI - Resonance ejection mass scan using dipole excitation with a non-integer frequency
ratio in a digital linear ion trap mass spectrometer.
PMID- 27501433
TI - Synthesis of Wavelength-shifting DNA Hybridization Probes by Using Photostable
Cyanine Dyes.
AB - In this protocol, we demonstrate a method for the synthesis of 2'-alkyne modified
deoxyribonucleic acid (DNA) strands by automated solid phase synthesis using
standard phosphoramidite chemistry. Oligonucleotides are post-synthetically
labeled by two new photostable cyanine dyes using copper-catalyzed click
chemistry. The synthesis of both donor and acceptor dye is described and is
performed in three consecutive steps. With the DNA as the surrounding
architecture, these two dyes undergo an energy transfer when they are brought
into close proximity by hybridization. Therefore, annealing of two single
stranded DNA strands is visualized by a change of fluorescence color. This color
change is characterized by fluorescence spectroscopy but can also be directly
observed by using a handheld ultraviolet (UV) lamp. The concept of a dual
fluorescence color readout makes these oligonucleotide probes excellent tools for
molecular imaging especially when the described photostable dyes are used.
Thereby, photobleaching of the imaging probes is prevented, and biological
processes can be observed in real time for a longer time period.
PMID- 27501434
TI - Practitioner Review: Psychological treatments for children and adolescents with
conduct disorder problems - a systematic review and meta-analysis.
AB - BACKGROUND: This meta-analysis evaluates the efficacy of nonpharmacological
treatments for conduct disorder (CD) problems in children and adolescents, based
on child, parent and teacher report. METHODS: PubMed, PsycINFO and EMBASE were
searched for peer-reviewed articles published between January 1970 and March
2015. Main inclusion criteria were nonpharmacological treatment, participants
younger than 18 years, clinical CD problems/diagnosis, randomized controlled
trials and inclusion of at least one CD problem-related outcome. Treatment
efficacy is expressed in effect sizes (ESs) calculated for each rater (parent,
teacher, self and blinded observer). RESULTS: Of 1,549 articles retrieved, 17
(published between June 2004 and January 2014) describing 19 interventions met
the inclusion criteria. All studies used psychological treatments; only three
studies included a blinded observer to rate CD problems. Most studies were of
very poor to fair quality. ESs were significant but small for parent-reported
outcomes (0.36, 95% CI = 0.27-0.47), teacher-reported outcomes (0.26, 95% CI =
0.12-0.49) and blinded observer outcomes (0.26, 95% CI = 0.06-0.47), and they
were nonsignificant for self-reported outcomes (-0.01, 95% CI = -0.25 to 0.23).
Comorbidity, gender, age, number of sessions, duration, intervention type,
setting, medication use or dropout percentage did not influence the effect of
treatment. CONCLUSIONS: Psychological treatments have a small effect in reducing
parent-, teacher- and observer-rated CD problems in children and adolescents with
clinical CD problems/diagnosis. There is not enough evidence to support one
specific psychological treatment over another. Future studies should investigate
the influence of participant characteristics (e.g. age of CD onset), use more
homogeneous outcome measures and allow better evaluation of study quality. Many
reports failed to provide detailed information to allow optimization of
psychological treatment strategies.
PMID- 27501435
TI - Does interim 18F-FDG-PET response-adapted therapy really benefit advanced-stage
Hodgkin lymphoma patients?
PMID- 27501436
TI - Activity concentration measurements using a conjugate gradient (Siemens xSPECT)
reconstruction algorithm in SPECT/CT.
AB - The interest in quantitative single photon emission computer tomography (SPECT)
shows potential in a number of clinical applications and now several vendors are
providing software and hardware solutions to allow 'SUV-SPECT' to mirror metrics
used in PET imaging. This brief technical report assesses the accuracy of
activity concentration measurements using a new algorithm 'xSPECT' from Siemens
Healthcare. SPECT/CT data were acquired from a uniform cylinder with 5, 10, 15
and 20 s/projection and NEMA image quality phantom with 25 s/projection. The NEMA
phantom had hot spheres filled with an 8 : 1 activity concentration relative to
the background compartment. Reconstructions were performed using parameters
defined by manufacturer presets available with the algorithm. The accuracy of
activity concentration measurements was assessed. A dose calibrator-camera cross
calibration factor (CCF) was derived from the uniform phantom data. In uniform
phantom images, a positive bias was observed, ranging from ~6% in the lower count
images to ~4% in the higher-count images. On the basis of the higher-count data,
a CCF of 0.96 was derived. As expected, considerable negative bias was measured
in the NEMA spheres using region mean values whereas positive bias was measured
in the four largest NEMA spheres. Nonmonotonically increasing recovery curves for
the hot spheres suggested the presence of Gibbs edge enhancement from resolution
modelling. Sufficiently accurate activity concentration measurements can easily
be measured on images reconstructed with the xSPECT algorithm without a CCF.
However, the use of a CCF is likely to improve accuracy further. A manual
conversion of voxel values into SUV should be possible, provided that the patient
weight, injected activity and time between injection and imaging are all known
accurately.
PMID- 27501437
TI - Controlling Molecular Ordering in Aqueous Conducting Polymers Using Ionic
Liquids.
AB - The molecular ordering of aqueous conducting polymers is controlled using a
rational method. By introducing various ionic liquids, which have designed
electrostatic interactions to PEDOT:PSS solutions, the evolution of the molecular
ordering of the PEDOT is manipulated. Consequently, highly ordered nanostructures
are achieved with a reduced pi-pi stacking distance of ~3.38 A and, thus, a
maximum sigmadc of ~2100 S cm-1 .
PMID- 27501438
TI - Cognitive behavioural therapy (CBT), third-wave CBT and interpersonal therapy
(IPT) based interventions for preventing depression in children and adolescents.
AB - BACKGROUND: Depression is common in young people. It has a marked negative impact
and is associated with self-harm and suicide. Preventing its onset would be an
important advance in public health. This is an update of a Cochrane review that
was last updated in 2011. OBJECTIVES: To determine whether evidence-based
psychological interventions (including cognitive behavioural therapy (CBT),
interpersonal therapy (IPT) and third wave CBT)) are effective in preventing the
onset of depressive disorder in children and adolescents. SEARCH METHODS: We
searched the specialised register of the Cochrane Common Mental Disorders Group
(CCMDCTR to 11 September 2015), which includes relevant randomised controlled
trials from the following bibliographic databases: The Cochrane Library (all
years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to
date). We searched conference abstracts and reference lists of included trials
and reviews, and contacted experts in the field. SELECTION CRITERIA: We included
randomised controlled trials of an evidence-based psychological prevention
programme compared with any comparison control for young people aged 5 to 19
years, who did not currently meet diagnostic criteria for depression. DATA
COLLECTION AND ANALYSIS: Two authors independently assessed trials for inclusion
and rated their risk of bias. We adjusted sample sizes to take account of cluster
designs and multiple comparisons. We contacted trial authors for additional
information where needed. We assessed the quality of evidence for the primary
outcomes using GRADE. MAIN RESULTS: We included 83 trials in this review. The
majority of trials (67) were carried out in school settings with eight in
colleges or universities, four in clinical settings, three in the community and
four in mixed settings. Twenty-nine trials were carried out in unselected
populations and 53 in targeted populations.For the primary outcome of depression
diagnosis at medium-term follow-up (up to 12 months), there were 32 trials with
5965 participants and the risk of having a diagnosis of depression was reduced
for participants receiving an intervention compared to those receiving no
intervention (risk difference (RD) -0.03, 95% confidence interval (CI) -0.05 to
0.01; P value = 0.01). We rated this evidence as moderate quality according to
the GRADE criteria. There were 70 trials (73 trial arms) with 13,829 participants
that contributed to the analysis for the primary outcome of depression symptoms
(self-rated) at the post-intervention time point, with results showing a small
but statistically significant effect (standardised mean difference (SMD) -0.21,
95% CI -0.27 to -0.15; P value < 0.0001). This effect persisted to the short-term
assessment point (up to three months) (SMD -0.31, 95% CI -0.45 to -0.17; P value
< 0.0001; 16 studies; 1558 participants) and medium-term (4 to 12 months)
assessment point (SMD -0.12, 95% CI -0.18 to -0.05; P value = 0.0002; 53 studies;
11,913 participants); however, the effect was no longer evident at the long-term
follow-up. We rated this evidence as low to moderate quality according to the
GRADE criteria.The evidence from this review is unclear with regard to whether
the type of population modified the overall effects; there was statistically
significant moderation of the overall effect for depression symptoms (P value =
0.0002), but not for depressive disorder (P value = 0.08). For trials implemented
in universal populations there was no effect for depression diagnosis (RD -0.01,
95% CI -0.03 to 0.01) and a small effect for depression symptoms (SMD -0.11, 95%
CI -0.17 to -0.05). For trials implemented in targeted populations there was a
statistically significantly beneficial effect of intervention (depression
diagnosis RD -0.04, 95% CI -0.07 to -0.01; depression symptoms SMD -0.32, 95% CI
0.42 to -0.23). Of note were the lack of attention placebo-controlled trials in
targeted populations (none for depression diagnosis and four for depression
symptoms). Among trials implemented in universal populations a number used an
attention placebo comparison in which the intervention consistently showed no
effect. AUTHORS' CONCLUSIONS: Overall the results show small positive benefits of
depression prevention, for both the primary outcomes of self-rated depressive
symptoms post-intervention and depression diagnosis up to 12 months (but not
beyond). Estimates of numbers needed to treat to benefit (NNTB = 11) compare well
with other public health interventions. However, the evidence was of moderate to
low quality using the GRADE framework and the results were heterogeneous.
Prevention programmes delivered to universal populations showed a sobering lack
of effect when compared with an attention placebo control. Interventions
delivered to targeted populations, particularly those selected on the basis of
depression symptoms, had larger effect sizes, but these seldom used an attention
placebo comparison and there are practical difficulties inherent in the
implementation of targeted programmes. We conclude that there is still not enough
evidence to support the implementation of depression prevention programmes.Future
research should focus on current gaps in our knowledge. Given the relative lack
of evidence for universal interventions compared with attention placebo controls
and the poor results from well-conducted effectiveness trials of universal
interventions, in our opinion any future such trials should test a depression
prevention programme in an indicated targeted population using a credible
attention placebo comparison group. Depressive disorder as the primary outcome
should be measured over the longer term, as well as clinician-rated depression.
Such a trial should consider scalability as well as the potential for the
intervention to do harm.
PMID- 27501439
TI - Beneficial effects of live and dead Salmonella-based vector strain on the course
of colitis in mice.
AB - : Dysbiosis of intestinal microbiota and hyperactive immune responses seem to be
crucial for the uncontrolled inflammation in inflammatory bowel diseases (IBD).
Modulation of the microbiome and immune stimulation of the intestinal epithelium
were suggested as therapeutic approaches. In this study, live attenuated and dead
bacterial cells of Salmonella Typhimurium SL7207 - a widely used bacterial vector
for gene therapy were administered in DSS-induced colitis in mice. C57BL/6 mice
were divided into four groups. The first group received pure water (CTRL). The
other three groups received 2% dextran sulphate sodium (DSS) to induce colitis.
Two DSS groups were treated with live attenuated (DSS live) or inactivated (DSS
dead) Salmonella by gastric gavage. Intake of 2% DSS caused weight loss in all
DSS groups compared to control mice with some improvement in DSS live group on
the last day of the experiment. Significantly longer colon and improved stool
consistency were reported in DSS live group, but not DSS dead group, when
compared with DSS. Significant enlargement of spleens was observed only in DSS
and DSS dead groups compared to control. Significant differences in stool
consistency, colon length and spleen enlargement were observed between DSS live
and DSS dead groups with beneficial effects of live bacteria. Interestingly,
significant decrease in myeloperoxidase activity was detected in both, DSS live
and DSS dead groups compared to the DSS group. On the basis of these results,
progression of colitis seems to be beneficially influenced not only by live
attenuated but to some extent also by inactivated Salmonella Typhimurium SL7207.
Our results provide evidence that Salmonella-based gene therapy vectors are able
to positively alter gut homeostasis during DSS-induced colitis. SIGNIFICANCE AND
IMPACT OF THE STUDY: Restoration of gut homeostasis has a great importance in
IBD. Here, we tested the nonspecific effect of the strain Salmonella Typhimurium
SL7207 on the course of colitis to find out whether the potential effect would be
mediated by activity of live bacterial cells or by bacterial structures that are
also present in dead bacteria. Live bacterial therapy of colitis showed a
beneficial effect on clinical signs as well as on macroscopic and inflammatory
markers of colitis. On the other hand, therapy with dead bacteria showed
inconsistent effects, negative in most clinical outcomes, positive especially in
myeloperoxidase activity. Our data indicate that the beneficial effect of
bacterial gene therapy vectors carrying therapeutic genes might be, at least
partially, caused by the bacterial vector instead of the therapeutic gene.
PMID- 27501440
TI - Survey of the anti-factor IX immunoglobulin profiles in patients with hemophilia
B using a fluorescence-based immunoassay.
AB - : Essentials Studies characterizing neutralizing antibodies (inhibitors) in
hemophilia B (HB) are lacking. The current study describes anti-factor (F) IX
antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a
strong positive correlation with Nijmegen-Bethesda results. These data will help
to more clearly define, predict, and treat alloantibody formation in HB. SUMMARY:
Background Hemophilia B (HB) is an inherited bleeding disorder caused by the
absence or dysfunction of coagulation factor IX (FIX). A subset of patients who
have HB develop neutralizing alloantibodies (inhibitors) against FIX after
infusion therapy. HB prevalence and the proportion of patients who develop
inhibitors are much lower than those for hemophilia A (HA), which makes studies
of inhibitors in patients with HB challenging due to the limited availability of
samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective
Evaluate the largest group of patients with inhibitor-positive HB studied to date
to assess the relationship between anti-FIX antibody profiles and inhibitor
formation. Methods A fluorescence immunoassay was used to detect anti-FIX
antibodies in plasma samples from 37 patients with HB. Results Assessments of
antibody profiles showed that anti-FIX IgG1-4 , IgA, and IgE were detected
significantly more often in patients with a positive Nijmegen-Bethesda assay
(NBA). All NBA-positive samples were positive for IgG4 . Anti-FIX IgG4
demonstrated a strong correlation with the NBA, while correlations were
significant, yet more moderate, for anti-FIX IgG1-2 and IgA. Conclusions The anti
FIX antibody profile in HB patients who develop inhibitors is diverse and
correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG4
is particularly relevant to functional inhibition. The anti-FIX fluorescence
immunoassay may serve as a useful tool to confirm the presence of antibodies in
patients who have low positive NBA results and to more clearly define, predict,
and treat alloantibody formation against FIX.
PMID- 27501442
TI - An improved non-Cartesian partially parallel imaging by exploiting artificial
sparsity.
AB - PURPOSE: To improve the performance of non-Cartesian partially parallel imaging
(PPI) by exploiting artificial sparsity, the generalized autocalibrating
partially parallel acquisitions (GRAPPA) operator for wider band lines (GROWL) is
taken as a specific example for explanation. THEORY: This work is based on the
GRAPPA-like PPI having an improved performance when the to-be-reconstructed image
is sparse in the image domain. METHODS: A systematic scheme is proposed to
artificially generate the sparse image for non-Cartesian trajectory. Using GROWL
as a specific non-Cartesian PPI method, artificial sparsity-enhanced GROWL (ARTS
GROWL) is used to demonstrate the efficiency of the proposed scheme. The ARTS
GROWL consists of three steps: 1) generating synthetic k-space data corresponding
to an image with smaller support, that is, artificial sparsity; 2) applying GROWL
to the synthetic k-space data from previous step; and 3) recovering the final
image from the reconstruction with the processed data. RESULTS: For simulation
and in vivo data, the experiments demonstrate that the proposed ARTS-GROWL
significantly reduces the reconstruction errors compared with the conventional
GROWL technique for the tested acceleration factors. CONCLUSION: Taking ARTS
GROWL, for instance, experimental results indicate that artificial sparsity
improved the signal-to-noise ratio and normalized root-mean-square error of non
Cartesian PPI. Magn Reson Med 78:271-279, 2017. (c) 2016 International Society
for Magnetic Resonance in Medicine.
PMID- 27501441
TI - Tau and spectraplakins promote synapse formation and maintenance through Jun
kinase and neuronal trafficking.
AB - The mechanisms regulating synapse numbers during development and ageing are
essential for normal brain function and closely linked to brain disorders
including dementias. Using Drosophila, we demonstrate roles of the microtubule
associated protein Tau in regulating synapse numbers, thus unravelling an
important cellular requirement of normal Tau. In this context, we find that Tau
displays a strong functional overlap with microtubule-binding spectraplakins,
establishing new links between two different neurodegenerative factors. Tau and
the spectraplakin Short Stop act upstream of a three-step regulatory cascade
ensuring adequate delivery of synaptic proteins. This cascade involves
microtubule stability as the initial trigger, JNK signalling as the central
mediator, and kinesin-3 mediated axonal transport as the key effector. This
cascade acts during development (synapse formation) and ageing (synapse
maintenance) alike. Therefore, our findings suggest novel explanations for
intellectual disability in Tau deficient individuals, as well as early synapse
loss in dementias including Alzheimer's disease.
PMID- 27501443
TI - Unconscious Affective Responses to Food.
AB - Affective or hedonic responses to food are crucial for humans, both
advantageously (e.g., enhancing survival) and disadvantageously (e.g., promoting
overeating and lifestyle-related disease). Although previous psychological
studies have reported evidence of unconscious cognitive and behavioral processing
related to food, it remains unknown whether affective reactions to food can be
triggered unconsciously and its relationship with daily eating behaviors. We
investigated these issues by using the subliminal affective priming paradigm.
Photographs of food or corresponding mosaic images were presented in the
peripheral visual field for 33 ms. Target photos of faces with emotionally
neutral expressions were then presented, and participants rated their preferences
for the faces. Eating behaviors were also assessed using questionnaires. The food
images, relative to the mosaics, increased participants' preference for
subsequent target faces. Furthermore, the difference in the preference induced by
food versus mosaic images was positively correlated with the tendency to engage
in external eating. These results suggest that unconscious affective reactions
are elicited by the sight of food and that these responses contribute to daily
eating behaviors related to overeating.
PMID- 27501444
TI - Cellular and Molecular Mechanisms of MT1-MMP-Dependent Cancer Cell Invasion.
AB - Metastasis is responsible for most cancer-associated deaths. Accumulating
evidence based on 3D migration models has revealed a diversity of invasive
migratory schemes reflecting the plasticity of tumor cells to switch between
proteolytic and nonproteolytic modes of invasion. Yet, initial stages of
localized regional tumor dissemination require proteolytic remodeling of the
extracellular matrix to overcome tissue barriers. Recent data indicate that
surface-exposed membrane type 1-matrix metalloproteinase (MT1-MMP), belonging to
a group of membrane-anchored MMPs, plays a central role in pericellular matrix
degradation during basement membrane and interstitial tissue transmigration
programs. In addition, a large body of work indicates that MT1-MMP is targeted to
specialized actin-rich cell protrusions termed invadopodia, which are responsible
for matrix degradation. This review describes the multistep assembly of actin
based invadopodia in molecular details. Mechanisms underlying MT1-MMP traffic to
invadopodia through endocytosis/recycling cycles, which are key to the invasive
program of carcinoma cells, are discussed.
PMID- 27501445
TI - Cell Competition: Mechanisms and Physiological Roles.
AB - Cell-competitive interactions are widespread in nature and determine the outcome
of a vast variety of biological processes. A particular class of competitive
interactions takes place when alterations in intrinsic cellular properties are
sensed nonautonomously by comparison between neighboring cells, resulting in the
selective elimination of one cell population. This type of cell competition was
first described four decades ago in developing epithelia of Drosophila. In the
last 15 years, further molecular and cellular analyses have provided essential
knowledge about the mechanisms, universality, and physiological relevance of cell
competition. The two main phenomena triggering cell competition are alterations
in cellular metabolic status and alterations in epithelial apico-basal polarity,
while other reported pathways are less characterized. Cell competition plays
essential roles in quality control, homeostasis, and repair of developing and
adult tissues, and depending on the context, it may function as a tumor
suppressing or tumor-promoting mechanism.
PMID- 27501446
TI - Transcriptional Control of Developmental Cell Behaviors.
AB - Tissue-specific transcription regulators emerged as key developmental control
genes, which operate in the context of complex gene regulatory networks (GRNs) to
coordinate progressive cell fate specification and tissue morphogenesis. We
discuss how GRNs control the individual cell behaviors underlying complex
morphogenetic events. Cell behaviors classically range from mesenchymal cell
motility to cell shape changes in epithelial sheets. These behaviors emerge from
the tissue-specific, multiscale integration of the local activities of universal
and pleiotropic effectors, which underlie modular subcellular processes including
cytoskeletal dynamics, cell-cell and cell-matrix adhesion, signaling, polarity,
and vesicle trafficking. Extrinsic cues and intrinsic cell competence determine
the subcellular spatiotemporal patterns of effector activities. GRNs influence
most subcellular activities by controlling only a fraction of the effector-coding
genes, which we argue is enriched in effectors involved in reading and processing
the extrinsic cues to contextualize intrinsic subcellular processes and canalize
developmental cell behaviors. The properties of the transcription-cell behavior
interface have profound implications for evolution and disease.
PMID- 27501447
TI - Focal Adhesion-Independent Cell Migration.
AB - Cell migration is central to a multitude of physiological processes, including
embryonic development, immune surveillance, and wound healing, and deregulated
migration is key to cancer dissemination. Decades of investigations have
uncovered many of the molecular and physical mechanisms underlying cell
migration. Together with protrusion extension and cell body retraction, adhesion
to the substrate via specific focal adhesion points has long been considered an
essential step in cell migration. Although this is true for cells moving on two
dimensional substrates, recent studies have demonstrated that focal adhesions are
not required for cells moving in three dimensions, in which confinement is
sufficient to maintain a cell in contact with its substrate. Here, we review the
investigations that have led to challenging the requirement of specific adhesions
for migration, discuss the physical mechanisms proposed for cell body
translocation during focal adhesion-independent migration, and highlight the
remaining open questions for the future.
PMID- 27501448
TI - Genotypes, Networks, Phenotypes: Moving Toward Plant Systems Genetics.
AB - One of the central goals in biology is to understand how and how much of the
phenotype of an organism is encoded in its genome. Although many genes that are
crucial for organismal processes have been identified, much less is known about
the genetic bases underlying quantitative phenotypic differences in natural
populations. We discuss the fundamental gap between the large body of knowledge
generated over the past decades by experimental genetics in the laboratory and
what is needed to understand the genotype-to-phenotype problem on a broader
scale. We argue that systems genetics, a combination of systems biology and the
study of natural variation using quantitative genetics, will help to address this
problem. We present major advances in these two mostly disconnected areas that
have increased our understanding of the developmental processes of flowering time
control and root growth. We conclude by illustrating and discussing the efforts
that have been made toward systems genetics specifically in plants.
PMID- 27501449
TI - The Lysosome as a Regulatory Hub.
AB - The lysosome has long been viewed as the recycling center of the cell. However,
recent discoveries have challenged this simple view and have established a
central role of the lysosome in nutrient-dependent signal transduction. The
degradative role of the lysosome and its newly discovered signaling functions are
not in conflict but rather cooperate extensively to mediate fundamental cellular
activities such as nutrient sensing, metabolic adaptation, and quality control of
proteins and organelles. Moreover, lysosome-based signaling and degradation are
subject to reciprocal regulation. Transcriptional programs of increasing
complexity control the biogenesis, composition, and abundance of lysosomes and
fine-tune their activity to match the evolving needs of the cell. Alterations in
these essential activities are, not surprisingly, central to the pathophysiology
of an ever-expanding spectrum of conditions, including storage disorders,
neurodegenerative diseases, and cancer. Thus, unraveling the functions of this
fascinating organelle will contribute to our understanding of the fundamental
logic of metabolic organization and will point to novel therapeutic avenues in
several human diseases.
PMID- 27501450
TI - Signaling and Polarized Communication Across the T Cell Immunological Synapse.
AB - T cells express a somatically recombined antigen receptor (alphabetaTCR) that is
calibrated during development to respond to changes in peptides displayed by
major histocompatibility complex proteins (pMHC) on the surface of antigen
presenting cells (APC). A key characteristic of pMHC for adaptive immunity is the
ability to sample internal states of cells and tissues to sensitively detect
changes associated with infection, cell derangement, or tissue injury. Physical T
cell-APC contact sets up an axis for polarization of TCR, adhesion molecules,
kinases, cytoskeletal elements, and organelles inherent in this mode of
juxtacrine signaling. The discovery of further lateral organization of the TCR
and adhesion molecules into radially symmetric compartments, the immunological
synapse, revealed an intersecting plane of symmetry and potential for regulated
symmetry breaking to control duration of T cell-APC interactions. In addition to
organizing signaling machinery, the immunological synapse directs the polarized
transport and secretion of cytokines and cytolytic agents across the synaptic
cleft and is a site for the generation and exocytic release of bioactive
microvesicles that can functionally affect recipient APC and other cells in the
environment. This machinery is coopted by retroviruses, and human immune
deficiency virus-1 may even use antigen-specific synapses for infection of
healthy T cells. Here, we discuss recent advances in the molecular and cell
biological mechanisms of immunological synapse assembly and signaling and its
role in intercellular communication across the synaptic cleft.
PMID- 27501451
TI - The Heidelberg Screen for Pattern Mutants of Drosophila: A Personal Account.
AB - In large-scale mutagenesis screens performed in 1979-1980 at the EMBL in
Heidelberg, we isolated mutations affecting the pattern or structure of the
larval cuticle in Drosophila. The 600 mutants we characterized could be assigned
to 120 genes and represent the majority of such genes in the genome. These
mutants subsequently provided a rich resource for understanding many fundamental
developmental processes, such as the transcriptional hierarchies controlling
segmentation, the establishment of cell states by signaling pathways, and the
differentiation of epithelial cells. Most of the Heidelberg genes are now
molecularly known, and many of them are conserved in other animals, including
humans. Although the screens were initially driven entirely by curiosity, the
mutants now serve as models for many human diseases. In this review, we describe
the rationale of the screening procedures and provide a classification of the
genes on the basis of their initial phenotypes and the subsequent molecular
analyses.
PMID- 27501452
TI - Fluorophore-binding RNA aptamers and their applications.
AB - Why image RNA? Of all the biological molecules, RNA exhibits the most diverse
range of functions. Evidence suggests that transcription produces a wide range of
noncoding RNAs (ncRNAs), both short (e.g., siRNAs, miRNAs) and long (e.g.,
telomeric RNAs) that regulate many aspects of gene expression, including the
epigenetic processes that underlie cell fate determination, polarization, and
morphogenesis. All these functions are realized through the exquisite temporal
and spatial control of RNA expression levels and the stability of specific RNAs
within well-defined sub-cellular compartments. Given the central importance of
RNA in dictating cell behavior via gene-related functions, there is a great
demand for RNA imaging methods so as to determine the composition of the cellular
'transcriptome' and to acquire a complete spatial-temporal profile of RNA
localization. Recent advances in fluorophore-binding RNA aptamers promise to
provide exactly this knowledge, which can ultimately advance our understanding of
cell function and behavior in conditions of health and disease, and in response
to external stimuli. WIREs RNA 2016, 7:843-851. doi: 10.1002/wrna.1383 For
further resources related to this article, please visit the WIREs website.
PMID- 27501453
TI - Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates
and Infants.
AB - Sirolimus is increasingly being used in neonates and infants, but the mechanistic
basis of age-dependent changes in sirolimus disposition has not been fully
addressed yet. In order to characterize the age-dependent changes, serial
sirolimus clearance (CL) estimates in individual young pediatric patients were
collected and analyzed by population modeling analysis. In addition, sirolimus
metabolite formation was also investigated to further substantiate the
corresponding age-dependent change in CYP3A activity. The increasing pattern over
time of allometrically size-normalized sirolimus CL estimates vs. age was well
described by a sigmoidal Emax model. This age-dependent increase was also
observed within each individual patient over a 4-year study period. CYP3A
dependent sirolimus metabolite formation changed in a similar fashion. This study
clearly demonstrates the rapid increase of sirolimus CL over time in neonates and
infants, indicating the developmental change. This developmental pattern can be
explained by a parallel increase in CYP3A metabolic activity.
PMID- 27501454
TI - The Swedish P-CAT: modification and exploration of psychometric properties of two
different versions.
AB - The aim of this study was to further investigate the psychometric properties
(with focus on construct validity and scale function) of the Swedish version of
the Person-centred Care Assessment Tool (P-CAT) in a sample consisting of staff
working in elderly care units (N = 142). The aim was also to further develop and
psychometrically test a modified, noncontext-specific version of the instrument
(mP-CAT) in a sample consisting of staff working in primary health care or within
home care for older people (N = 182). Principal component analysis with varimax
rotation initially suggested a three-factor solution for the P-CAT, explaining
55.96% of variance. Item 13 solely represented one factor wherefore this solution
was rejected. A final 2-factor solution, without item 13, had a cumulative
explained variance of 50.03%. All communalities were satisfactory (>0.3), and
alpha values for both first factor (items 1-6, 11) and second factor (items 7-10,
12) were found to be acceptable. Principal component analysis with varimax
rotation suggested a final 2-factor solution for the mP-CAT explaining 46.15% of
the total variance with communalities ranging from 0.263 to 0.712. Cronbach's
alpha for both factors was found to be acceptable (>0.7). This study suggests a 2
factor structure for the P-CAT and an exclusion of item 13. The results indicated
that the modified noncontext-specific version, mP-CAT, seems to be a valid
measure. Further psychometric testing of the mP-CAT is however needed in order to
establish the instrument's validity and reliability in various contexts.
PMID- 27501455
TI - Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET
Imaging.
AB - Development of predictable in vitro tumor models is a challenging task due to the
enormous complexity of tumors in vivo. The closer the resemblance of these models
to human tumor characteristics, the more suitable they are for drug-development
and -testing. In the present study, we generated a complex 3D lung tumor test
system based on acellular rat lungs. A decellularization protocol was established
preserving the architecture, important ECM components and the basement membrane
of the lung. Human lung tumor cells cultured on the scaffold formed cluster and
exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a
reduced proliferation rate compared to respective 2D culture. Additionally,
employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron
emission tomography (FDG-PET) these tumor cell cluster could be detected and
tracked over time. This approach allowed monitoring of a targeted tyrosine kinase
inhibitor treatment in the in vitro lung tumor model non-destructively.
Surprisingly, FDG-PET assessment of single tumor cell cluster on the same
scaffold exhibited differences in their response to therapy, indicating
heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test
system features important characteristics of tumors and its microenvironment and
allows monitoring of tumor growth and -metabolism in combination with functional
imaging. In longitudinal studies, new therapeutic approaches and their long-term
effects can be evaluated to adapt treatment regimes in future.
PMID- 27501456
TI - Etiological Subgroups of Small-for-Gestational-Age: Differential
Neurodevelopmental Outcomes.
AB - OBJECTIVES: It remains unclear why substantial variations in neurodevelopmental
outcomes exist within small-for-gestational-age (SGA) children. We prospectively
compared 5-y neurodevelopmental outcomes across SGA etiological subgroups.
METHODS: Children born SGA (N = 1050) from U.S. Early Childhood Longitudinal
Study-Birth Cohort (2001-2007) was divided into etiological subgroups by each of
7 well-established prenatal risk factors. We fit linear regression models to
compare 5-y reading, math, gross motor and fine motor scores across SGA
subgroups, adjusting for socio-demographic confounders. RESULTS: Compared to
singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading
(adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06]) and
math (-2.22 [-3.61, -0.84]) scores. These disadvantages in reading and math
existed only among multiple-birth SGA subgroup without ovulation stimulation
(reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44]), but not among those
with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86,
3.12]). Compared to singleton SGA subgroup without maternal smoking and
inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of
maternal smoking and inadequate gestational weight gain (GWG) had lower mean
reading (-4.81 [-8.50, -1.12]) and math (-2.95 [-5.51, -0.38]) scores. These
differences were not mediated by Apgar score. CONCLUSIONS: Multiple-birth SGA
subgroups (vs. singleton SGA) or singleton SGA subgroup with co-occurrence of
smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking
and inadequate gestational weight gain) have poorer cognitive development up to 5
y.
PMID- 27501457
TI - Cel5I, a SLH-Containing Glycoside Hydrolase: Characterization and Investigation
on Its Role in Ruminiclostridium cellulolyticum.
AB - Ruminiclostridium cellulolyticum (Clostridium cellulolyticum) is a mesophilic
cellulolytic anaerobic bacterium that produces a multi-enzymatic system composed
of cellulosomes and non-cellulosomal enzymes to degrade plant cell wall
polysaccharides. We characterized one of the non-cellulosomal enzymes, Cel5I,
composed of a Family-5 Glycoside Hydrolase catalytic module (GH5), a tandem of
Family-17 and -28 Carbohydrate Binding Modules (CBM), and three S-layer
homologous (SLH) modules, where the latter are expected to anchor the protein on
the cell surface. Cel5I is the only putative endoglucanase targeting the cell
surface as well as the only putative protein in R. cellulolyticum containing
CBM17 and/or CBM28 modules. We characterized different recombinant structural
variants from Cel5I. We showed that Cel5I has an affinity for insoluble
cellulosic substrates through its CBMs, that it is the most active endoglucanase
on crystalline cellulose of R. cellulolyticum characterized to date and mostly
localized in the cell envelope of R. cellulolyticum. Its role in vivo was
analyzed using a R. cellulolyticum cel5I mutant strain. Absence of Cel5I in the
cell envelope did not lead to a significant variation of the phenotype compared
to the wild type strain. Neither in terms of cell binding to cellulose, nor for
its growth on crystalline cellulose, thus indicating that the protein has a
rather subtle role in tested conditions. Cel5I might be more important in a
natural environment, at low concentration of degradable glucose polymers, where
its role might be to generate higher concentration of short cellodextrins close
to the cell surface, facilitating their uptake or for signalization purpose.
PMID- 27501458
TI - Serological Evidence of Lyssaviruses among Bats on Southwestern Indian Ocean
Islands.
AB - We provide serological evidence of lyssavirus circulation among bats on
southwestern Indian Ocean (SWIO) islands. A total of 572 bats belonging to 22
species were collected on Anjouan, Mayotte, La Reunion, Mauritius, Mahe and
Madagascar and screened by the Rapid Fluorescent Focus Inhibition Test for the
presence of neutralising antibodies against the two main rabies related
lyssaviruses circulating on the African continent: Duvenhage lyssavirus (DUVV)
and Lagos bat lyssavirus (LBV), representing phylogroups I and II, respectively.
A total of 97 and 42 sera were able to neutralise DUVV and LBV, respectively. No
serum neutralised both DUVV and LBV but most DUVV-seropositive bats (n = 32/220)
also neutralised European bat lyssavirus 1 (EBLV-1) but not Rabies lyssavirus
(RABV), the prototypic lyssavirus of phylogroup I. These results highlight that
lyssaviruses belonging to phylogroups I and II circulate in regional bat
populations and that the putative phylogroup I lyssavirus is antigenically closer
to DUVV and EBLV-1 than to RABV. Variation between bat species, roost sites and
bioclimatic regions were observed. All brain samples tested by RT-PCR specific
for lyssavirus RNA were negative.
PMID- 27501459
TI - Racial-Ethnic Disparities in Opioid Prescriptions at Emergency Department Visits
for Conditions Commonly Associated with Prescription Drug Abuse.
AB - Prescription drug abuse is a growing problem nationally. In an effort to curb
this problem, emergency physicians might rely on subjective cues such as race
ethnicity, often unknowingly, when prescribing opioids for pain-related
complaints, especially for conditions that are often associated with drug-seeking
behavior. Previous studies that examined racial-ethnic disparities in opioid
dispensing at emergency departments (EDs) did not differentiate between
prescriptions at discharge and drug administration in the ED. We examined racial
ethnic disparities in opioid prescription at ED visits for pain-related
complaints often associated with drug-seeking behavior and contrasted them with
conditions objectively associated with pain. We hypothesized a priori that racial
ethnic disparities will be present among opioid prescriptions for conditions
associated with non-medical use, but not for objective pain-related conditions.
Using data from the National Hospital Ambulatory Medical Care Survey for 5 years
(2007-2011), the odds of opioid prescription during ED visits made by non-elderly
adults aged 18-65 for 'non-definitive' conditions (toothache, back pain and
abdominal pain) or 'definitive' conditions (long-bone fracture and kidney stones)
were modeled. Opioid prescription at discharge and opioid administration at the
ED were the primary outcomes. We found significant racial-ethnic disparities,
with non-Hispanic Blacks being less likely (adjusted odds ratio ranging from 0.56
0.67, p-value < 0.05) to receive opioid prescription at discharge during ED
visits for back pain and abdominal pain, but not for toothache, fractures and
kidney stones, compared to non-Hispanic whites after adjusting for other
covariates. Differential prescription of opioids by race-ethnicity could lead to
widening of existing disparities in health, and may have implications for
disproportionate burden of opioid abuse among whites. The findings have important
implications for medical provider education to include sensitization exercises
towards their inherent biases, to enable them to consciously avoid these biases
from defining their practice behavior.
PMID- 27501460
TI - Functional requirements of cellular differentiation: lessons from Bacillus
subtilis.
AB - Successful execution of differentiation programs requires cells to assess
multitudes of internal and external cues and respond with appropriate gene
expression programs. Here, we review how Bacillus subtilis sporulation network
deals with these tasks focusing on the lessons generalizable to other systems.
With feedforward loops controlling both production and activation of downstream
transcriptional regulators, cells achieve ultrasensitive threshold-like
responses. The arrangement of sporulation network genes on the chromosome and
transcriptional feedback loops allow coordination of sporulation decision with
DNA-replication. Furthermore, to assess the starvation conditions without sensing
specific metabolites, cells respond to changes in their growth rates with
increased activity of sporulation master regulator. These design features of the
sporulation network enable cells to robustly decide between vegetative growth and
sporulation.
PMID- 27501461
TI - An up-date on Giardia and giardiasis.
AB - Giardia intestinalis is a non-invasive protozoan parasite infecting the upper
small intestine causing acute, watery diarrhea or giardiasis in 280 million
people annually. Asymptomatic infections are equally common and recent data have
suggested that infections even can be protective against other diarrheal
diseases. Most symptomatic infections resolve spontaneously but infections can
lead to chronic disease and treatment failures are becoming more common world
wide. Giardia infections can also result in irritable bowel syndrome (IBS) and
food allergies after resolution. Until recently not much was known about the
mechanism of giardiasis or the cause of post-giardiasis syndromes and treatment
failures, but here we will describe the recent progress in these areas.
PMID- 27501463
TI - Hydroxypropyl-beta-CD vs. its alpha-homologue for a 3D modified polyrotaxane
network formation and properties: the relationship between modified CD and
polymer revealed through comparison.
AB - The threading mechanism of the hydroxypropyl-cyclodextrin (Hy-CD)/tetrahedron
like poly(ethylene glycol) (tetra-PEG) based host-guest complex and the
relationship between Hy-CD and poly(ethylene oxide) (PEO) in the three
dimensional modified polyrotaxane (PR) formed by the complex were revealed
through the comparison between Hy-beta-CD/tetra-PEG and Hy-alpha-CD/tetra-PEG
based systems from the macroscopic material view to the microscopic molecular
view. The complexation between Hy-CD and tetra-PEG in water experiences a
threading-dethreading-rethreading process which is controlled by the
intermolecular interaction intensity or molecular hindrance depending on the feed
ratio of Hy-CD to tetra-PEG. In the 3D modified PR, the methyl group of the Hy
part on one Hy-CD can insert into the cavity of the adjacent Hy-CD and interacts
with both the interior surface of the cavity and the PEO segment within the
cavity if the cavity of Hy-CD is large enough. The threaded Hy-CD in the PR
straightens the chain of PEO and suppresses the segment motion of the PEO. With
the decrease of the cavity size of Hy-CD, the degree of suppression on the
segment motion of PEO increases. Hy-CD threaded on the PEO chain can also deform
when the 3D modified PR is compressed, and the degree of deformation increases
with the increase of the cavity size of Hy-CD. These results of the modified
CD/PEG based complex system set it apart from the unmodified CD/PEG based one,
and reveal the structure-property relationship of this new type of Hy-CD/tetra
PEG based 3D modified PR material.
PMID- 27501462
TI - Epitaxial Growth of Perovskite Strontium Titanate on Germanium via Atomic Layer
Deposition.
AB - Atomic layer deposition (ALD) is a commercially utilized deposition method for
electronic materials. ALD growth of thin films offers thickness control and
conformality by taking advantage of self-limiting reactions between vapor-phase
precursors and the growing film. Perovskite oxides present potential for next
generation electronic materials, but to-date have mostly been deposited by
physical methods. This work outlines a method for depositing SrTiO3 (STO) on
germanium using ALD. Germanium has higher carrier mobilities than silicon and
therefore offers an alternative semiconductor material with faster device
operation. This method takes advantage of the instability of germanium's native
oxide by using thermal deoxidation to clean and reconstruct the Ge (001) surface
to the 2*1 structure. 2-nm thick, amorphous STO is then deposited by ALD. The STO
film is annealed under ultra-high vacuum and crystallizes on the reconstructed Ge
surface. Reflection high-energy electron diffraction (RHEED) is used during this
annealing step to monitor the STO crystallization. The thin, crystalline layer of
STO acts as a template for subsequent growth of STO that is crystalline as-grown,
as confirmed by RHEED. In situ X-ray photoelectron spectroscopy is used to verify
film stoichiometry before and after the annealing step, as well as after
subsequent STO growth. This procedure provides framework for additional
perovskite oxides to be deposited on semiconductors via chemical methods in
addition to the integration of more sophisticated heterostructures already
achievable by physical methods.
PMID- 27501464
TI - Templated Synthesis of Uniform Perovskite Nanowire Arrays.
AB - While the chemical composition of semiconducting metal halide perovskites can be
precisely controlled in thin films for photovoltaic devices, the synthesis of
perovskite nanostructures with tunable dimensions and composition has not been
realized. Here, we describe the templated synthesis of uniform perovskite
nanowires with controlled diameter (50-200 nm). Importantly, by providing three
examples (CH3NH3PbI3, CH3NH3PbBr3, and Cs2SnI6), we show that this process is
composition general and results in oriented nanowire arrays on transparent
conductive substrates.
PMID- 27501465
TI - An integrative theory-driven framework for evaluating travel training programs.
AB - Since the 1970s, travel training programs, which provide a short-term training to
people with disabilities and older people to teach them independent travel skills
required to use fixed-route transportation, have spread across the United States.
But the authors note that currently, there is no integrative framework for
evaluating the training programs, although it is crucial for improving program
implementation and developing knowledge and theories related to travel training.
Therefore, this research aims to build an integrative theory-driven evaluation
framework of the programs on the basis of prior studies on travel training and
the literature on program evaluation and learning and training theories. The
framework considers (1) a wide range of key elements related to the delivery
systems and outcomes of travel training; (2) diverse stakeholders that engage in
designing, operating, and assessing travel training; and (3) the short-term,
intermediate, and long-term outcomes of the programs. Based on the framework, the
authors develop a flexible logic model for travel training programs to help
scholars and practitioners design and conduct actual evaluation studies. Thus,
this research is expected to make theoretical and practical contributions to
theory-driven program evaluation and travel training programs.
PMID- 27501466
TI - Lessons learned while building a trauma-informed public behavioral health system
in the City of Philadelphia.
AB - Exposure to traumatic experiences among youth is a serious public health concern.
A trauma-informed public behavioral health system that emphasizes core principles
such as understanding trauma, promoting safety, supporting consumer autonomy,
sharing power, and ensuring cultural competence, is needed to support traumatized
youth and the providers who work with them. This article describes a case study
of the creation and evaluation of a trauma-informed publicly funded behavioral
health system for children and adolescents in the City of Philadelphia (the
Philadelphia Alliance for Child Trauma Services; PACTS) using the Exploration,
Preparation, Implementation, and Sustainment (EPIS) as a guiding framework. We
describe our evaluation of this effort with an emphasis on implementation
determinants and outcomes. Implementation determinants include inner context
factors, specifically therapist knowledge and attitudes (N=114) towards evidence
based practices. Implementation outcomes include rate of PTSD diagnoses in
agencies over time, number of youth receiving TF-CBT over time, and penetration
(i.e., number of youth receiving TF-CBT divided by the number of youth screening
positive on trauma screening). We describe lessons learned from our experiences
building a trauma-informed public behavioral health system in the hopes that this
case study can guide other similar efforts.
PMID- 27501469
TI - Length distributions of Au-catalyzed and In-catalyzed InAs nanowires.
AB - We present experimental data on the length distributions of InAs nanowires grown
by chemical beam epitaxy with Au catalyst nanoparticles obtained by thermal
dewetting of Au film, Au colloidal nanoparticles and In droplets. Poissonian
length distributions are observed in the first case. Au colloidal nanoparticles
produce broader and asymmetric length distributions of InAs nanowires. However,
the distributions can be strongly narrowed by removing the high temperature
annealing step. The length distributions for the In-catalyzed growth are instead
very broad. We develop a generic model that is capable of describing the observed
behaviors by accounting for both the incubation time for nanowire growth and
secondary nucleation of In droplets. These results allow us to formulate some
general recipes for obtaining more uniform length distributions of III-V
nanowires.
PMID- 27501467
TI - High-Density Lipoprotein Biogenesis: Defining the Domains Involved in Human
Apolipoprotein A-I Lipidation.
AB - The first step in removing cholesterol from a cell is the ATP-binding cassette
transporter 1 (ABCA1)-driven transfer of cholesterol to lipid-free or lipid-poor
apolipoprotein A-I (apoA-I), which yields cholesterol-rich nascent high-density
lipoprotein (nHDL) that then matures in plasma to spherical, cholesteryl ester
rich HDL. However, lipid-free apoA-I has a three-dimensional (3D) conformation
that is significantly different from that of lipidated apoA-I on nHDL. By
comparing the lipid-free apoA-I 3D conformation of apoA-I to that of 9-14 nm
diameter nHDL, we formulated the hypothetical helical domain transitions that
might drive particle formation. To test the hypothesis, ten apoA-I mutants were
prepared that contained two strategically placed cysteines several of which could
form intramolecular disulfide bonds and others that could not form these bonds.
Mass spectrometry was used to identify amino acid sequence and intramolecular
disulfide bond formation. Recombinant HDL (rHDL) formation was assessed with this
group of apoA-I mutants. ABCA1-driven nHDL formation was measured in four mutants
and wild-type apoA-I. The mutants contained cysteine substitutions in one of
three regions: the N-terminus, amino acids 34 and 55 (E34C to S55C), central
domain amino acids 104 and 162 (F104C to H162C), and the C-terminus, amino acids
200 and 233 (L200C to L233C). Mutants were studied in the locked form, with an
intramolecular disulfide bond present, or unlocked form, with the cysteine thiol
blocked by alkylation. Only small amounts of rHDL or nHDL were formed upon
locking the central domain. We conclude that both the N- and C-terminal ends
assist in the initial steps in lipid acquisition, but that opening of the central
domain was essential for particle formation.
PMID- 27501470
TI - The Novel Application of Genomic Profiling Assays to Shorten Inactive Status for
Potential Kidney Transplant Recipients With Breast Cancer.
AB - The concern about cancer recurrence has traditionally resulted in delaying kidney
transplantation for 2-5 years after a cancer diagnosis in patients who are
otherwise eligible for transplant. This period of inactive status to observe the
tumor biology can result in significant morbidity and decreased quality of life
for patients with end-stage renal disease (ESRD). We reported the novel
application of genomic profiling assays in breast cancer to identify low-risk
cancers in two patients with ESRD who were able to have the mandatory inactive
status eliminated prior to kidney transplantation.
PMID- 27501468
TI - MicroRNAs 29b and 181a down-regulate the expression of the norepinephrine
transporter and glucocorticoid receptors in PC12 cells.
AB - MicroRNAs are short non-coding RNAs that provide global regulation of gene
expression at the post-transcriptional level. Such regulation has been found to
play a role in stress-induced epigenetic responses in the brain. The
norepinephrine transporter (NET) and glucocorticoid receptors are closely related
to the homeostatic integration and regulation after stress. Our previous studies
demonstrated that NET mRNA and protein levels in rats are regulated by chronic
stress and by administration of corticosterone, which is mediated through
glucocorticoid receptors. Whether miRNAs are intermediaries in the regulation of
these proteins remains to be elucidated. This study was undertaken to determine
possible regulatory effects of miRNAs on the expression of NET and glucocorticoid
receptors in the noradrenergic neuronal cell line. Using computational target
prediction, we identified several candidate miRNAs potentially targeting NET and
glucocorticoid receptors. Western blot results showed that over-expression of miR
181a and miR-29b significantly repressed protein levels of NET, which is
accompanied by a reduced [3 H] norepinephrine uptake, and glucocorticoid
receptors in PC12 cells. Luciferase reporter assays verified that both miR-181a
and miR-29b bind the 3'UTR of mRNA of NET and glucocorticoid receptors.
Furthermore, exposure of PC12 cells to corticosterone markedly reduced the
endogenous levels of miR-29b, which was not reversed by the application of
glucocorticoid receptor antagonist mifepristone. These observations indicate that
miR-181a and miR-29b can function as the negative regulators of NET and
glucocorticoid receptor translation in vitro. This regulatory effect may be
related to stress-induced up-regulation of the noradrenergic phenotype, a
phenomenon observed in stress models and depressive patients. This study
demonstrated that miR-29b and miR-181a, two short non-coding RNAs that provide
global regulation of gene expression, markedly repressed protein levels of
norepinephrine (NE) transporter and glucocorticoid receptor (GR), as well as NE
uptake by binding the 3'UTR of their mRNAs in PC12 cells. Also, exposure of cells
to corticosterone significantly reduced miR-29b levels through a GR-independent
way.
PMID- 27501471
TI - Long-Term Follow-Up of Isolated Epicardial Left Ventricular Lead Implant Using a
Minithoracotomy Approach for Cardiac Resynchronization Therapy.
AB - BACKGROUND: Transvenous left ventricular (LV) lead placement for cardiac
resynchronization therapy is unsuccessful in 5-10% of reported cases. These
patients may benefit from isolated surgical placement of an epicardial LV lead
via minithoracotomy approach. AIM: To evaluate the success of this approach at
long-term follow-up. METHODS: Retrospective evaluation of all consecutive
patients undergoing isolated epicardial LV lead placement after failed
transvenous attempt over a 6-year period. Data collected on baseline parameters,
procedural details, and outcome at follow-up (hospital stay, complications,
mortality, and clinical response). RESULTS: Forty-two patients underwent
epicardial lead implant. Five died within 1 year (11.9%): two (4.8%) died within
30-days post op (one from intraoperative hemorrhage, the other from multiple
organ failure); 39 (95.1%) were admitted to the high dependency unit and
transferred to the ward <24 hours. Median hospital stay was 3.4 +/- 1.9 days. The
overall complication rate was 17.5% (n = 7): 15.0% (n = 6) short term and 2.5% (n
= 1) long term; these included three (7.5%) LV noncapture events all treated with
reprogramming. There were two (5.0%) wound infections requiring oral antibiotics
and two (5.0%) device infections requiring intravenous antibiotics (one had
device resiting, the other developed septic shock requiring intensive care
admission). Assessment of clinical response was possible in 34 (81.0%) at follow
up: 21 (61.8%) were responders and 13 (28.2%) nonresponders with no significant
differences between these groups; no clinical predictors of response were
identified. CONCLUSION: Isolated epicardial LV lead implant using minithoracotomy
is relatively safe and effective at successful LV pacing. Response rate and
postoperative recovery at long-term follow-up are reasonable in these high-risk
patients.
PMID- 27501472
TI - Resonantly Enhanced Second-Harmonic Generation Using III-V Semiconductor All
Dielectric Metasurfaces.
AB - Nonlinear optical phenomena in nanostructured materials have been challenging our
perceptions of nonlinear optical processes that have been explored since the
invention of lasers. For example, the ability to control optical field
confinement, enhancement, and scattering almost independently allows nonlinear
frequency conversion efficiencies to be enhanced by many orders of magnitude
compared to bulk materials. Also, the subwavelength length scale renders phase
matching issues irrelevant. Compared with plasmonic nanostructures, dielectric
resonator metamaterials show great promise for enhanced nonlinear optical
processes due to their larger mode volumes. Here, we present, for the first time,
resonantly enhanced second-harmonic generation (SHG) using gallium arsenide
(GaAs) based dielectric metasurfaces. Using arrays of cylindrical resonators we
observe SHG enhancement factors as large as 10(4) relative to unpatterned GaAs.
At the magnetic dipole resonance, we measure an absolute nonlinear conversion
efficiency of ~2 * 10(-5) with ~3.4 GW/cm(2) pump intensity. The polarization
properties of the SHG reveal that both bulk and surface nonlinearities play
important roles in the observed nonlinear process.
PMID- 27501473
TI - Admission hyperglycemia in sepsis is associated with poor outcomes: where do we
go from here?
PMID- 27501474
TI - Outcomes with frontline nilotinib treatment in Turkish patients with newly
diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic
phase.
AB - OBJECTIVE: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the
treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP).
This study was the first prospective evaluation of the efficacy and safety of
nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint
of the study was the rate of major molecular response (MMR; BCR-ABL1 <= 0.1% on
the International Scale [BCR-ABL1(IS)]) by 12 months. METHODS: Patients with
newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This
analysis was based on the first 12 months of follow-up in a 24-month study.
RESULTS AND CONCLUSIONS: Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%)
achieved MMR and 22.3% achieved a deep molecular response of MR(4.5) (BCR
ABL1(IS) <= 0.0032%) by 12 months. During the first year of treatment, 1 patient
progressed to blast crisis and 2 patients died. Safety results were consistent
with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently
reported nonhematologic AEs of any grade were elevations in bilirubin, alanine
aminotransferase, and triglycerides. These results support the use of nilotinib
300 mg twice daily as a standard-of-care treatment option for patients with newly
diagnosed CML-CP.
PMID- 27501475
TI - Comparative performance of oral midazolam clearance and plasma 4beta
hydroxycholesterol to explain interindividual variability in tacrolimus
clearance.
AB - AIMS: We compared the CYP3A4 metrics weight-corrected midazolam apparent oral
clearance (MDZ Cl/F/W) and plasma 4beta-hydroxycholesterol/cholesterol (4beta
OHC/C) as they relate to tacrolimus (TAC) Cl/F/W in renal transplant recipients.
METHODS: For a cohort of 147 patients, 8 h area under the curve (AUC) values for
TAC and oral MDZ were calculated besides measurement of 4beta-OHC/C. A subgroup
of 70 patients additionally underwent intravenous erythromycin breath test (EBT)
and were administered the intravenous MDZ probe. All patients were genotyped for
common polymorphisms in CYP3A4, CYP3A5 and P450 oxidoreductase, among others.
RESULTS: MDZ Cl/F/W, 4beta-OHC/C/W, EBT and TAC Cl/F/W were all moderately
correlated (r = 0.262-0.505). Neither MDZ Cl/F/W nor 4beta-OHC/C/W explained
variability in TAC Cl/F/W in CYP3A5 expressors (n = 29). For CYP3A5 non
expressors (n = 118), factors explaining variability in TAC Cl/F/W in a MDZ-based
model were MDZ Cl/F/W (R2 = 0.201), haematocrit (R2 = 0.139), TAC formulation
(R2 = 0.107) and age (R2 = 0.032; total R2 = 0.479). In the 4beta-OHC/C/W
based model, predictors were 4beta-OHC/C/W (R2 = 0.196), haematocrit (R2 =
0.059) and age (R2 = 0.057; total R2 = 0.312). When genotype information was
ignored, predictors of TAC Cl/F/W in the whole cohort were 4beta-OHC/C/W (R2 =
0.167), MDZ Cl/F/W (R2 = 0.045); Tac QD formulation (R2 = 0.036), and
haematocrit (R2 = 0.032; total R2 = 0.315). 4beta-OHC/C/W, but not MDZ Cl/F/W,
was higher in CYP3A5 expressors because it was higher in CYP3A4*1b carriers,
which were almost all CYP3A5 expressors. CONCLUSIONS: A MDZ-based model explained
more variability in TAC clearance in CYP3A5 non-expressors. However, 4beta
OHC/C/W was superior in a model in which no genotype information was available,
likely because 4beta-OHC/C/W was influenced by the CYP3A4*1b polymorphism.
PMID- 27501476
TI - Crystal structures of SIRT3 reveal that the alpha2-alpha3 loop and alpha3-helix
affect the interaction with long-chain acyl lysine.
AB - SIRT1-7 play important roles in many biological processes and age-related
diseases. In addition to a NAD(+) -dependent deacetylase activity, they can
catalyze several other reactions, including the hydrolysis of long-chain fatty
acyl lysine. To study the binding modes of sirtuins to long-chain acyl lysines,
we solved the crystal structures of SIRT3 bound to either a H3K9-myristoylated-
or a H3K9-palmitoylated peptide. Interaction of SIRT3 with the palmitoyl group
led to unfolding of the alpha3-helix. The myristoyl and palmitoyl groups bind to
the C-pocket and an allosteric site near the alpha3-helix, respectively. We found
that the residues preceding the alpha3-helix determine the size of the C-pocket.
The flexibility of the alpha2-alpha3 loop and the plasticity of the alpha3-helix
affect the interaction with long-chain acyl lysine.
PMID- 27501477
TI - Inhibitor development after liver transplantation in congenital factor VII
deficiency.
AB - Congenital factor VII (FVII) deficiency is the commonest type of the rare
bleeding disorders. Very few cases of congenital FVII deficiency developed
inhibitor and liver transplant is considered as definitive treatment. In the
literature, twelve patients with congenital FVII deficiency developed inhibitors.
Two had spontaneous resolution of inhibitors and one did not respond to high dose
recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in
congenital FVII patients, seven patients underwent liver transplant with good
prognosis. We report a 5-year-old girl with confirmed severe congenital FVII
deficiency since neonatal period. She suffered from recurrent intracranial
bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age
of 4, she continued to show persistent deranged clotting profile and was found to
have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa
replacement.
PMID- 27501478
TI - Perioperative complications and outcomes in children with cerebral palsy
undergoing scoliosis surgery.
AB - INTRODUCTION: Neuromuscular scoliosis is a known risk factor for postoperative
complications after corrective spine surgery. Few studies have looked at the
preoperative factors affecting postoperative complications in children with
cerebral palsy. AIM: The aim of this study was to examine the factors that might
influence postoperative course in patients with cerebral palsy undergoing spine
surgery for scoliosis. METHODS: Nineteen case notes of children with cerebral
palsy who had spine surgery (2008-2014) were reviewed retrospectively.
Preoperative comorbidities and postoperative complications were noted and
complications were classified as major and minor. RESULTS: Thirteen out of 19
(68.4%) patients had two or more systemic comorbidities. Most common
comorbidities included reflux and seizure disorder. Nine patients (49%) had at
least one major complication. About 5/19 patients had respiratory complications
requiring ventilation and 4/19 had massive blood loss. A higher incidence of
postoperative major complication was recorded in the group with two systemic
comorbidities as compared to those with less than two systemic comorbidities (47%
vs 16%). Both patients who had a single-stage anterior release and posterior
fixation had a major complication. CONCLUSION: Presence of two or more
comorbidities and thoracotomy are risk factors for perioperative complications in
children with cerebral palsy undergoing surgery for scoliosis correction.
PMID- 27501479
TI - Unique Three-Dimensional InP Nanopore Arrays for Improved Photoelectrochemical
Hydrogen Production.
AB - Ordered three-dimensional (3D) nanostructure arrays hold promise for high
performance energy harvesting and storage devices. Here, we report the
fabrication of InP nanopore arrays (NPs) in unique 3D architectures with
excellent light trapping characteristic and large surface areas for use as highly
active photoelectrodes in photoelectrochemical (PEC) hydrogen evolution devices.
The ordered 3D NPs were scalably synthesized by a facile two-step etching process
of (1) anodic etching of InP in neutral 3 M NaCl electrolytes to realize
nanoporous structures and (2) wet chemical etching in HCl/H3PO4 (volume ratio of
1:3) solutions for removing the remaining top irregular layer. Importantly, we
demonstrated that the use of neutral electrolyte of NaCl instead of other
solutions, such as HCl, in anodic etching of InP can significantly passivate the
surface states of 3D NPs. As a result, the maximum photoconversion efficiency
obtained with ~15.7 MUm thick 3D NPs was 0.95%, which was 7.3 and 1.4 times
higher than that of planar and 2D NPs. Electrochemical impedance spectroscopy and
photoluminescence analyses further clarified that the improved PEC performance
was attributed to the enhanced charge transfer across 3D NPs/electrolyte
interfaces, the improved charge separation at 3D NPs/electrolyte junction, and
the increased PEC active surface areas with our unique 3D NP arrays.
PMID- 27501480
TI - The impact of personalisation on people from Chinese backgrounds: qualitative
accounts of social care experience.
AB - The limited research that considers people from black and minority ethnic
communities' experiences of personalisation tends to focus on personal budgets
rather than personalisation per se. This article provides an opportunity to hear
the voices of people from Chinese backgrounds and their experiences of
personalisation. The study used individual semi-structured interviews and focus
groups to collect data from physically disabled people from Chinese backgrounds
who lived in England, were aged between 18 and 70, and received social care. Data
were analysed using an iterative and thematic approach, with early analysis
informing the subsequent analytical rounds. The findings reveal that
personalisation has the potential to transform the lives of people from Chinese
backgrounds, especially when tailored support is available for people to
understand and access personal budgets and put them to creative use. However, the
impact of personalisation is barely evident because few eligible individuals
access personal budgets or participate in co-production. This is related to a
lack of encouragement for service users to become genuine partners in
understanding, designing, commissioning and accessing a diverse range of social
care services to meet their cultural and social care needs.
PMID- 27501481
TI - Admission hyperglycemia and outcome in ICU patients with sepsis.
PMID- 27501482
TI - Robust anti-nociceptive effects of monoacylglycerol lipase inhibition in a model
of osteoarthritis pain.
AB - BACKGROUND AND PURPOSE: Chronic pain is often a symptom of knee osteoarthritis
(OA) for which current analgesics are either inadequate or are associated with
serious side effects. The endocannabinoid system may offer alternative targets
for pain relief. We evaluated the effects of a potent and selective
monoacylglycerol (MAG) lipase inhibitor (MJN110) on OA pain behaviour, spinal
mechanisms of action and joint histopathology in the rat. EXPERIMENTAL APPROACH:
Intra-articular injection of monosodium iodoacetate (MIA) models OA pain and
mimics clinical joint pathology. Effects of MJN110 on MIA-induced weight-bearing
asymmetry and lowered paw withdrawal thresholds (PWTs), changes in spinal gene
expression and brain levels of relevant lipids were determined. KEY RESULTS:
Acute MJN110 (5 mg.kg-1 ) significantly reversed MIA-induced weight-bearing
asymmetry (MIA/vehicle: 68 +/- 6 g; MIA/MJN110: 35 +/- 4 g) and lowered
ipsilateral PWTs (MIA/vehicle: 7 +/- 0.8 g; MIA/MJN110: 11 +/- 0.6 g), via both
CB1 and CB2 receptors. Repeated treatment with MJN110 (5 mg.kg-1 ) resulted in
anti-nociceptive tolerance. A lower dose of MJN110 (1 mg.kg-1 ) acutely inhibited
pain behaviour, which was maintained for 1 week of repeated administration but
had no effect on joint histology. MJN110 significantly inhibited expression of
membrane-associated PGE synthase-1 in the ipsilateral dorsal horn of the spinal
cord of MIA rats, compared with vehicle-treated MIA rats. Both doses of MJN110
significantly elevated brain levels of the endocannabinoid 2
arachidonoylglycerol. CONCLUSIONS AND IMPLICATIONS: Our data support further
assessment of the therapeutic potential of MAG lipase inhibitors for the
treatment of OA pain.
PMID- 27501483
TI - Stigmatization toward irritable bowel syndrome and inflammatory bowel disease in
an online cohort.
AB - BACKGROUND: Stigma is associated with many negative health outcomes. Research has
examined perceived and internalized stigma in individuals with irritable bowel
syndrome (IBS) and inflammatory bowel disease (IBD), but less has been done to
evaluate levels of enacted stigma associated with these conditions. The aim of
this study was to evaluate the presence of enacted stigma toward IBS and IBD in
the general population compared to an adult-onset asthma (AOA) control group.
METHODS: Participants were recruited via social media and a research-dedicated
website and completed all measures online. Participants were randomized to one of
six clinical vignettes: (i) IBD male, (ii) IBD female, (iii) IBS male, (iv) IBS
female, (v) AOA male, or (vi) AOA female. Participants read the assigned vignette
and then completed measures of emotional empathy, level of familiarity, and
enacted stigma. KEY RESULTS: Participants reported higher levels of enacted
stigma toward IBS compared to both IBD and AOA. No differences in stigma were
found between IBD and AOA. Higher levels of familiarity were most strongly
correlated with reduced IBD-related stigma, with weaker but still significant
correlations between level of familiarity and IBS and AOA. Higher levels of
emotional empathy were associated with reduced stigma for IBD, IBS, and AOA.
CONCLUSIONS & INFERENCES: Individuals with IBS experience greater levels of
enacted stigma compared to IBD and AOA. This finding is consistent with previous
research that has shown greater levels of perceived and internalized stigma in
IBS compared to IBD.
PMID- 27501485
TI - One step effective removal of Congo Red in chitosan nanoparticles by
encapsulation.
AB - Chitosan nanoparticles (CNPs) were prepared with ionotropic gelation between
chitosan and tripolyphosphate for the removal of Congo Red. The production of
chitosan nanoparticles and the dye removal process was carried out in one-step.
The removal efficiency of Congo Red by encapsulation within chitosan from the
aqueous solution and its storage stability are examined at different pH values.
The influence of some parameters such as the initial dye concentration, pH value
of the dye solution, electrolyte concentration, tripolyphosphate concentration,
mixing time and speed on the encapsulation is examined. Congo Red removal
efficiency and encapsulation capacity of chitosan nanoparticles were determined
as above 98% and 5107mg Congo Red/g chitosan, respectively.
PMID- 27501486
TI - Etchant-based design of gold tip apexes for plasmon-enhanced Raman
spectromicroscopy.
AB - In this paper, we gain insight into the design and optimization of plasmonic
(metallic) tips prepared with dc-pulsed voltage electrochemical etching gold
wires, provided that, a duty cycle is self-tuned. Physically, it means that
etching electrolyte attacks the gold wire equally for all pulse lengths,
regardless of its surface shape. Etchant effect on the reproducibility of a
curvature radius of the tip apex is demonstrated. It means that the gold conical
tips can be designed chemically with a choice of proper etchant electrolyte. It
is suggested to use a microtomed binary polymer blend consisting of polyamide and
low density polyethylene, as a calibration grating, for optimizing and
standardizing tip-enhanced Raman scattering performance.
PMID- 27501487
TI - Geriatric periodontology: how the need to care for the aging population can
influence the future of the dental profession.
AB - The world's population is aging, and it has been estimated that by 2050, the
number of people 65 years of age and older will reach 1.5 billion. The aging
population will be affected by noncommunicable chronic diseases, including
diabetes mellitus, cardiovascular disease and cognitive impairment. This
important demographic shift includes a reduction in tooth loss/edentulism,
particularly in older adults of the developed countries in North America, western
Europe and north-east Asia. Therefore, in the future, dental providers will be
required to care for an expanded number of older adults who have retained teeth
and are medically complex. As the linkage of oral disease and systemic disease
has focused on the relationship of periodontitis and noncommunicable chronic
diseases, a broad review of 'geriatric periodontology' is both timely and
important. This volume of Periodontology 2000 covers a range of subjects under
this heading. Included are the demographics of an aging world; the effect of
aging on stem cell function in the periodontium; the periodontal microbiota
associated with aging; the host response in the periodontium of aging
individuals; an analysis of the prevalence of periodontitis in the USA on a
national, state-wide and community basis; differentiation of physiologic oral
aging from disease; treatment of periodontal disease in older adults; implant
therapy for older patients; oral disease and the frailty syndrome; the
relationship of tooth loss to longevity and life expectancy; and the relationship
of periodontal disease to noncommunicable chronic diseases. Although 'geriatric
dentistry' is not a recognized specialty in dentistry, and 'geriatric
periodontology' is a descriptive title, the subject of this volume of
Periodontology 2000 is critical to the future of clinical dentistry, dental
public health and dental research. Any comprehensive focus on older patients can
only be accomplished with an emphasis on interprofessional education and
practice. If embraced, this shift will allow the dental profession to be more
closely aligned with the larger health-care environment, and can improve both
oral health and health outcomes for patients seen in the dental office.
PMID- 27501488
TI - The aging population: demographics and the biology of aging.
AB - Epidemiologic studies show that 11% of the world's population is over 60 years of
age; this is projected to increase, by 2050, to 22% of the population. Oral aging
is a current focus of several organizations including the Federation Dentaire
Internationale, the World Health Organization and the American and Japanese
Dental Associations. In their Tokyo Declaration, the Japanese Association
identified the elderly population as one of its main target groups. One of the
WHO goals is for each person to retain more than 20 teeth by age 80, despite the
fact that the prevalence of periodontal disease is continuously rising as the
population is aging. Every species has its own characteristic lifespan, which is
determined by its evolutionary history and is modified by multiple diverse
factors, including biological mechanisms. In humans, the gradual accumulation of
products of cellular metabolism and extensive DNA damage contribute to the aging
process. Aging is thought to be associated with a low-grade inflammatory
phenotype in mammals, called 'inflammaging', and is the result of autophagic
capacity impairing so-called 'housekeeping activities' in the cells, resulting in
protein aggregation, mitochondrial dysfunction and oxidative stress. Delayed stem
cell proliferation, associated with aging, may impact the maintenance and
survival of a living being, but excessive proliferation could also result in
depleted reserves of stem cells. Studies are needed to address the association of
delayed cell proliferation and wound healing with the onset of periodontal
diseases and response to treatment. The effects of systemic diseases,
medications, psychological effects and decreased interest or ability in
performing oral-hygiene practices are thought to result in periodontal diseases,
and ultimately in tooth loss, in aged individuals. Together with an aging
population comes a responsibility for 'healthy' and 'successful' aging. This
article describes the changing global demographic profile and the effects of an
aging society on the prevalence and incidence of periodontal diseases. We review
the definitions of normal and successful aging, the principles of geriatric
medicine and the highlights of biological aging at cellular, tissue and systems
levels.
PMID- 27501489
TI - From restoration to regeneration: periodontal aging and opportunities for
therapeutic intervention.
AB - With the march of time our bodies start to wear out: eyesight fades, skin loses
its elasticity, teeth and bones become more brittle and injuries heal more
slowly. These universal features of aging can be traced back to our stem cells.
Aging has a profound effect on stem cells: DNA mutations naturally accumulate
over time and our bodies have evolved highly specialized mechanisms to remove
these damaged cells. Whilst obviously beneficial, this repair mechanism also
reduces the pool of available stem cells and this, in turn, has a dramatic effect
on tissue homeostasis and on our rate of healing. Simply put: fewer stem cells
means a decline in tissue function and slower healing. Despite this seemingly
intractable situation, research over the past decade now demonstrates that some
of the effects of aging are reversible. Nobel prize-winning research demonstrates
that old cells can become young again, and lessons learned from these experiments
in-a-dish are now being translated into human therapies. Scientists and
clinicians around the world are identifying and characterizing methods to
activate stem cells to reinvigorate the body's natural regenerative process. If
this research in dental regenerative medicine pans out, the end result will be
tissue homeostasis and healing back to the levels we appreciated when we were
young.
PMID- 27501491
TI - Aging, inflammation, immunity and periodontal disease.
AB - The increased prevalence and severity of periodontal disease have long been
associated with aging, such that this oral condition affects the majority of the
adult population over 50 years of age. Although the immune system is a critical
component for maintaining health, aging can be characterized by quantitative and
qualitative modifications of the immune system. This process, termed
'immunosenescence', is a progressive modification of the immune system that leads
to greater susceptibility to infections, neoplasia and autoimmunity, presumably
reflecting the prolonged antigenic stimulation and/or stress responses that occur
across the lifespan. Interestingly, the global reduction in the host capability
to respond effectively to these challenges is coupled with a progressive increase
in the general proinflammatory status, termed 'inflammaging'. Consistent with the
definition of immunosenescence, it has been suggested that the cumulative effect
of prolonged exposure of the periodontium to microbial challenge is, at least in
part, a contributor to the effects of aging on these tissues. Thus, it has also
been hypothesized that alterations in the function of resident immune and
nonimmune cells of the periodontium contribute to the expression of inflammaging
in periodontal disease. Although the majority of aging research has focused on
the adaptive immune response, it is becoming increasingly clear that the innate
immune compartment is also highly affected by aging. Thus, the phenomenon of
immunosenescence and inflammaging, expressed as age-associated changes within the
periodontium, needs to be more fully understood in this era of precision and
personalized medicine and dentistry.
PMID- 27501490
TI - The subgingival periodontal microbiota of the aging mouth.
AB - Different mechanisms have been hypothesized to explain the increase in prevalence
and severity of periodontitis in older adults, including shifts in the
periodontal microbiota. However, the actual impact of aging on the composition of
subgingival biofilms remains unclear. In the present article, we provide an
overview of the composition of the subgingival biofilm in older adults and the
potential effects of age on the oral microbiome. In particular, this review
covers the following topics: (i) the oral microbiota of an aging mouth; (ii) the
effects of age and time on the human oral microbiome; (iii) the potential impact
of inflammaging and immunosenescence in the host-oral microbiota interactions;
and (iv) the relationship of the aging oral microbiota and Alzheimer's disease.
Finally, we present analyses of data compiled from large clinical studies that
evaluated the subgingival microbiota of periodontally healthy subjects and
patients with periodontitis from a wide age spectrum (20-83 years of age).
PMID- 27501492
TI - Periodontitis prevalence in adults >= 65 years of age, in the USA.
AB - The older adult population is growing rapidly in the USA and it is expected that
by 2040 the number of adults >= 65 years of age will have increased by about 50%.
With the growth of this subpopulation, oral health status, and periodontal status
in particular, becomes important in the quest to maintain an adequate quality of
life. Poor oral health can have a major impact, leading to tooth loss, pain and
discomfort, and may prevent older adults from chewing food properly, often
leading to poor nutrition. Periodontitis is monitored in the USA at the national
level as part of the Healthy People 2020 initiative. In this report, we provide
estimates of the overall burden of periodontitis among adults >= 65 years of age
and after stratification according to sociodemographic factors, modifiable risk
factors (such as smoking status), the presence of other systemic conditions (such
as diabetes) and access to dental care. We also estimated the burden of
periodontitis within this age group at the state and local levels. Data from the
National Health and Nutrition Examination Survey 2009/2010 and 2011/2012 cycles
were analyzed. Periodontal measures from both survey cycles were based on a full
mouth periodontal examination. Nineteen per cent of adults in this subpopulation
were edentulous. The mean age was 73 years, 7% were current smokers, 8% lived
below the 100% Federal Poverty Level and < 40% had seen a dentist in the past
year. Almost two-thirds (62.3%) had one or more sites with >= 5 mm of clinical
attachment loss and almost half had at least one site with probing pocket depth
of >= 4 mm. We estimated the lowest prevalence of periodontitis in Utah (62.3%)
and New Hampshire (62.6%) and the highest in New Mexico, Hawaii, and the District
of Columbia each with a prevalence of higher than 70%. Overall, periodontitis is
highly prevalent in this subpopulation, with two-thirds of dentate older adults
affected at any geographic level. These findings provide an opportunity to
determine how the overall health-care management of older adults should consider
the improvement of their oral health conditions. Many older adults do not have
dental insurance and are also likely to have some chronic conditions, which can
adversely affect their oral health.
PMID- 27501493
TI - The aging mouth: differentiating normal aging from disease.
AB - Aging is the physiologic change that occurs over time. In humans, this change
occurs at different rates and are related to lifestyle, environment and genetics.
It can be challenging to differentiate normal aging from disease. In the oral
cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping
and fracture lines, and a darker color. The pulp chamber and canals are reduced
in size as a result of the deposition of secondary dentin. Coronal or root
caries, however, represent disease. A limited amount of periodontal attachment
loss occurs in association with aging, usually manifesting as recession on the
buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the
population, with the peak incidence being observed at 35-40 years of age. Changes
to the mucosal tissue that occur with age include reduced wound-healing capacity.
However, environmental factors, such as smoking, dramatically increase the risk
of mucosal pathology. Reduced salivary gland function is often seen in
association with medication usage, as well as with disorders such as diabetes
mellitus. Both medication use and chronic disorders are more common in older
adults. Masticatory function is of particular importance for older adults.
Maintenance of a nutritionally complete diet is important for avoiding sarcopenia
and the frailty syndrome. Successful oral aging is associated with adequate
function and comfort. A reduced, but functional, dentition of 20 teeth in
occlusion has been proposed as a measure of successful oral aging. Healthy oral
aging is important to healthy aging from both biological and social perspectives.
PMID- 27501494
TI - Treatment of periodontal disease in older adults.
AB - Within the next 40 years the number of older adults worldwide will more than
double. This will impact periodontal treatment needs and presents a challenge to
health-care providers and governments worldwide, as severe periodontitis has been
reported to be the sixth most prevalent medical condition in the world. Older
adults (>= 80 years of age) who receive regular dental care retain more teeth
than those who do not receive such care, but routine general dental care for
these individuals is not sufficient to prevent the progression of periodontitis
with the same degree of success as in younger individuals. There is a paucity of
data on the efficacy of different periodontal therapies for older individuals.
However, considering the higher prevalence of chronic medical conditions seen in
older adults, it cannot be assumed that periodontal therapy will yield the same
degree of success seen in younger individuals. Furthermore, medications can
influence the status of the periodontium and the delivery of periodontal care. As
an example, anticoagulant drugs are common among older patients and may be a
contraindication to certain treatments. Newer anticoagulants will, however,
facilitate surgical intervention in older patients. Furthermore, prescription
medications taken for chronic conditions, such as osteoporosis and cardiovascular
diseases, can affect the periodontium in a variety of ways. In summary,
consideration of socio-economic factors, general health status and multiple-drug
therapies will, in the future, be an important part of the management of
periodontitis in older adults.
PMID- 27501495
TI - Implants for the aged patient: biological, clinical and sociological
considerations.
AB - Until recently, age, particularly old age, was considered a contraindication to
the placement of dental implants. However, this was based largely on anecdotal
dogma rather than on empirical information. This review considers the biological,
clinical and socio-economic implications of implants placed in the aged
population. Aging has been shown to have an influence on the biological aspects
of soft- and hard-tissue wound healing and tissue remodeling, which may influence
the establishment and maintenance of implant integration. However, information to
date indicates that age should not be an a priori contraindication for implant
placement and there is good evidence to indicate that dental implants can be
placed successfully in the elderly with good clinical and socio-economic
outcomes.
PMID- 27501496
TI - Oral health and the frailty syndrome.
AB - The frailty syndrome is an ever-growing area of study among older adults because
of its association with an increased risk of falls, hospitalization,
institutionalization, dependency and mortality. Frailty is neither a disease nor
a disability but is better understood as a medical syndrome of multisystem
dysregulation that results in a diminished ability to overcome everyday
stressors. The prevalence of frailty in any given population can vary widely, in
part because of the way in which it is defined and measured, but in general it is
higher among women and in those with advanced age and declining health. Whilst it
is largely understood that older adults will differ biologically, psychologically
and socially, and that each of these domains can impact oral health, we are only
beginning to investigate how the mouth is affected in frailty. Given that both
hard and soft structures contribute to oral health and disease status among older
adults with varying degrees of impairment and disability, frailty adds yet
another dimension to be considered. This paper will discuss how frailty can
influence and be influenced by oral disorders, as well as the potential
relationship to oral neglect and the resultant consequences among this vulnerable
population.
PMID- 27501497
TI - Tooth loss as a predictor of shortened longevity: exploring the hypothesis.
AB - Many factors contribute to human tooth loss, including oral hygiene practices,
trauma, smoking, health status, socio-economic status and individual preferences.
Loss of teeth impairs quality-of-life measures, including the eating of most
foods that require full masticatory function. A recent study of centenarians
found that at age 65-74 years, those who lived to be 100 had a lower rate of
edentulism than did younger members of their birth cohort at ages 65-74 years.
Oral health was consistent with compression of morbidity toward the end of life.
This article explores the hypothesis that factors associated with oral disease
and noncommunicable diseases may increase the risk of tooth loss and lead to
diminished longevity as a result of multifactorial interactions. It specifically
addresses two critical questions. The first is: 'Can we conclude that the number
of teeth in aging humans can affect longevity and life expectancy?' The answer is
yes. The second is: 'Is tooth loss a predictor of shortened longevity?' Again,
the answer is yes. Edentulism and partial edentulism are discussed as a
disability, and how the philosophy/belief systems of dental providers and
patients toward retaining teeth influences the outcome of tooth loss is also
examined. Osteoporosis and cognitive impairment provide examples of modifying
risk factors.
PMID- 27501498
TI - Oral inflammation and infection, and chronic medical diseases: implications for
the elderly.
AB - Oral diseases, such as caries and periodontitis, not only have local effects on
the dentition and on tooth-supporting tissues but also may impact a number of
systemic conditions. Emerging evidence suggests that poor oral health influences
the initiation and/or progression of diseases such as atherosclerosis (with
sequelae including myocardial infarction and stoke), diabetes mellitus and
neurodegenerative diseases (such as Alzheimer's disease, rheumatoid arthritis and
others). Aspiration of oropharyngeal (including periodontal) bacteria causes
pneumonia, especially in hospitalized patients and the elderly, and may influence
the course of chronic obstructive pulmonary disease. This article addresses
several pertinent aspects related to the medical implications of periodontal
disease in the elderly. There is moderate evidence that improved oral hygiene may
help prevent aspiration pneumonia in high-risk patients. For other medical
conditions, because of the absence of well-designed randomized clinical trials in
elderly patients, no specific guidance can be provided regarding oral hygiene or
periodontal interventions that enhance the medical management of older adults.
PMID- 27501499
TI - Biopeptides with antioxidant and anti-inflammatory potential in the prevention
and treatment of diabesity disease.
AB - Diabesity is the leading cause of modern, chronic disease. In 2012, diabetes
killed 1.2 million people worldwide and its global prevalence exceeded 347
million people, and it is expected that it will increase to 540 million by 2030.
Because of this health imperative, it is also linked to increasing obesity. The
role of the inflammatory process and oxidative stress in the pathophysiology of
these diseases is widely documented. This paper review, using data from major
databases, the role of biopeptides with antioxidant and anti-inflammatory
activity as a potential aid for the prevention and treatment of diabesity, since
the mechanisms of action mentioned directly affect oxidative stress and the
characteristic imbalance of the inflammatory process of this disease. Some of
these studies have demonstrated beneficial results in relation to oxidative
stress and proinflammatory markers. However, the role of biopeptides, in relation
to oxidative stress and inflammatory biomarkers, remains unclear and represents a
potentially fruitful area for further research in the health area.
PMID- 27501500
TI - Evaluation of the anti-diarrheal activity of the hydromethanolic root extract of
Rhus tripartita (Ucria) (Anacardiacae).
AB - INTRODUCTION: Rhus tripartita (Anacardiacae) is a plant which is traditionally
used for the treatment of ulcer and diarrhea in Tunisia. However, the scientific
basis for this usage has not been well established. The core aim of the present
study is to evaluate the antidiarrheal activity of Rhus tripartita root
methanolic extract (RRE). MATERIAL AND METHODS: The antidiarrheal activity of RRE
oral doses (50, 100, 200 and 300mg/kg) was evaluated using the castor oil-induced
diarrhea, the intestinal fluid emptying method and the normal intestinal transit
test. The antibacterial activity was tested against four pathogenic bacteria
using two methods. The RRE was also phytochemical studied. RESULTS: Diarrhea
experiments showed a protective effect of the RRE which produced a significant
(p<0.05) and dose-dependent reduction of all the diarrhea parameters. It delayed
the onset of diarrhea, produced a significant decrease in the frequency of
defecation and the diarrhea score severity and decreased the volume of intestinal
fluid induced by castor oil as well as the propulsion intestinal transit. The
effect of the extract at the highest dose (300mg/kg) was similar to that of
loperamide, the standard anti-diarrheal drug (10mg/kg). The anti-bacterial
activity test showed that RRE exhibited a great inhibition activity against four
pathogenic bacteria strains (Esherichia coli, Salmonella typhimurium, Salmonella
argenosa, Staphylococcus aureus). Oral administration of the extract up to 3g/kg
did not produce any acute toxicity in rats. The preliminary phytochemical
screening of the RRE revealed the presence of flavonoids, tannins, and
polyphenols. CONCLUSION: Results showed that RRE at 300mg/kg possesses the
highest anti-diarrheal activity possibly mediated by the inhibitory effects on
gastrointestinal propulsion and intestinal fluid accumulation.
PMID- 27501501
TI - The Urtica dioica extract enhances sensitivity of paclitaxel drug to MDA-MB-468
breast cancer cells.
AB - INTRODUCTION: Due to the chemo resistant nature of cancer cells and adverse
effects of current therapies, researchers are looking for the most efficient
therapeutic approach which has the lowest side effects and the highest toxicity
on cancer cells. The aim of the present study was to investigate the synergic
effect of Urtica dioica extract in combination with paclitaxel on cell death and
invasion of human breast cancer MDA-MB-468 cell line. MATERIALS AND METHODS: To
determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT
assay was performed. The scratch test was exploited to assess the effects of
Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The
expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes
were quantified using qRT-PCR and western blot performed for snail-1expression.
The effects of plant extract, Paclitaxel alone and combination on different
phases of cell cycle was analyzed using flow cytometry. RESULTS: Results of MTT
assay showed that Urtica dioica significantly destroyed cancer cells.
Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted
in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay
exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and
combination on migration of MDA-MB-468 cell line. Our findings also demonstrated
that the extract substantially decreased the Snail-1 and related gene expression.
Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by
deregulating Cdc2 and wee1. CONCLUSIONS: Our results demonstrated that the
dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also,
Urtica dioica extract substantially increased sensitivity of breast cancer cells
to paclitaxel. Therefore, it can be used as a potential candidate for treatment
of breast cancer with paclitaxel.
PMID- 27501502
TI - MiR-622 functions as a tumor suppressor and directly targets E2F1 in human
esophageal squamous cell carcinoma.
AB - PURPOSE: MicroRNA-622 has been proven down-regulated in many human malignancies
and correlated with tumor progression. However, its role in esophageal squamous
cell carcinoma (ESCC) is still unclear. The aim of this study was to explore the
expression and function of miR-622 in ESCC. METHODS: Using quantitative RT-PCR,
we detected miR-622 expression in ESCC cell lines and primary tumor tissues. The
association of miR-622 expression with clinicopathological factors and prognosis
was also analyzed. Then, the effects of miR-622 on the biological behavior of
ESCC cells were investigated. At last, the potential regulatory function of miR
622 on E2F1 expression was confirmed. RESULTS: miR-622 was found to be down
regulated in ESCC tissues and cell lines. Decreased miR-622 expression was
closely correlated with aggressive clinicopathological features and poor overall
survival. Multivariate regression analysis corroborated that low level of miR-622
expression was an independent unfavourable prognostic factor for patients with
ESCC. Up-regulation of miR-622 could significantly reduce ESCC cell
proliferation, enhance cell apoptosis, and impair cell invasion and migration in
vitro, while down-regulation of miR-622 showed opposite effects. Further, E2F1
was confirmed as a direct target of miR-622 by using Luciferase Reporter Assay.
CONCLUSIONS: These findings indicate that miR-622 may act as a tumor suppressor
in ESCC and would serve as a potential therapy target for this disease.
PMID- 27501503
TI - Shedding light on the gray zone.
PMID- 27501504
TI - Effect of metronidazole use on tacrolimus concentrations in transplant patients
treated for Clostridium difficile.
AB - BACKGROUND: Two case reports suggest that metronidazole treatment for Clostridium
difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary
objective of this study was to determine the clinical significance of this
potential interaction in transplant patients receiving CDI treatment. Currently,
no robust literature exists to estimate a magnitude of pharmacokinetic
interaction between metronidazole and TAC. METHODS: In this retrospective study,
the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid
organ transplant patients were investigated. The primary outcome was to determine
the difference in dose-normalized TAC levels between baseline and symptom
resolution in patients treated with metronidazole or vancomycin. The secondary
outcome was to determine the difference in dose-normalized TAC levels at baseline
and CDI diagnosis. RESULTS: The average change in log-transformed dose-normalized
TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n =
35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the
groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference
was found between dose-normalized TAC levels at CDI diagnosis and baseline (P =
0.37). CONCLUSION: CDI treatment with metronidazole was not associated with a
>30% increase in TAC levels compared with vancomycin. Both treatment groups
required TAC dose adjustments to maintain goal TAC levels and those treated with
metronidazole did not require a significantly greater dose adjustment.
PMID- 27501505
TI - Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable
or recurrent gastric cancer (JFMC36-0701).
AB - BACKGROUND: Lentinan (LNT) is a purified beta-1, 3-glucan that augments immune
responses. The present study was conducted to assess the efficacy of LNT in
combination with S-1 as a first-line treatment for unresectable or recurrent
gastric cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned to
receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival
(OS). Secondary end-points were time-to-treatment failure (TTF), overall response
rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT
binding monocytes in peripheral blood prior to treatment were analysed for the
biomarker assessment. RESULTS: One hundred and fifty-four and 155 patients were
randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median
OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P
< 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups,
respectively. The incidences of haematologic and non-haematologic adverse events
were similar, and no significant changes in QOL scores were observed during the
treatment in both groups. In a subpopulation of patients with LNT-binding
monocytes >=2%, patients who received more than two cycles of chemotherapy showed
a longer survival time in the S-1 plus LNT group. CONCLUSIONS: OS did not improve
and TTF was significantly worse in the S-1 plus LNT group as compared with the S
1-only group. This study showed no efficacy of LNT when combined with S-1
treatment in patients with unresectable or recurrent gastric cancer. CLINICAL
TRIAL REGISTRATION ID NUMBER: UMIN 000000574.
PMID- 27501506
TI - Systemic review: Radiation therapy alone in medical non-operable endometrial
carcinoma.
AB - BACKGROUND AND PURPOSE: Radiotherapy is a good option for inoperable and frail
patients diagnosed with endometrial cancer. Because of the lack of large
multicentre trials, a systematic review was performed in an attempt to get an
overview on the feasibility and efficacy of this specific approach. MATERIALS AND
METHODS: We performed a bibliographic search for articles in English or French
which were published in PubMed from the start of this database in January 1969 to
identify publications on radiation therapy (RT) as single treatment for localised
non-operable carcinoma of the endometrium. The review was completed following the
preferred reporting items for systematic reviews and meta-analyses (PRISMA)
guidelines. RESULTS: Twenty-five reports containing 2694 patients treated with RT
as single treatment were identified that fulfilled the selection criteria.
Disease-specific survival (DSS) at 5 years was reported for a cohort of 1322
(49.1%) patients. The combined DSS for this group of patients was 78.5% (range:
68.4-92%; 95% confidence interval: 74.5-82.5). External beam radiation therapy
(EBRT) combined with brachytherapy (BT) was used in 1278 patients (47.4%), BT
alone in 1383 patients (51.3%), and EBRT alone in 33 patients (1.2%). The average
occurrence of grade III or worse late toxicity was 3.7% for EBRT + BT, 2.8% for
BT alone, and 1.2% for EBRT alone. CONCLUSIONS: RT is in terms of disease control
and toxicity, an acceptable option for non-surgical candidate patients.
Prospective multicentre randomised or observational trials are needed to validate
these results.
PMID- 27501507
TI - Combined low-dose ipilimumab and pembrolizumab after sequential ipilimumab and
pembrolizumab failure in advanced melanoma.
AB - With the wide use of anti-PD-1 therapy, an increasing number of patients progress
under treatment. Combined immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies
induces higher response rates as first-line treatment in comparison to single
agent therapy, however, with substantial toxicity since the combination of
ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) induced 55% grade 3/4 treatment
related adverse events and treatment discontinuation rates of 39%. In this case
series, we investigated the efficacy and toxicity of the combined immunotherapy
with low-dose ipilimumab (1 mg/kg) plus pembrolizumab (2 mg/kg) in patients with
metastatic melanoma with progressive disease under sequential monotherapy with
both agents. All patients had received at least three lines of treatment, 78% of
patients were M1c, and 67% had brain metastases. Stable disease was observed in 3
out of 9 patients with a median overall survival of 8 months after double
checkpoint inhibition. No treatment-related grade 3/4 adverse events occurred,
and none of the patients needed to discontinue the treatment due to toxicity.
Further trials are needed to investigate combined immunotherapy as rescue
treatment in heavily pretreated melanoma patients to find optimal dosage in
regard to outcome and toxicity.
PMID- 27501508
TI - LVAD implantation following repair of acute postmyocardial infarction ventricular
septal defect.
AB - Ventricular septal defect (VSD) is a life-threatening complication of myocardial
infarction (MI). Mortality is highest if VSD repair occurs within seven days
following MI. We report a case of post-MI VSD stabilized with peripheral veno
arterial extracorporeal membrane oxygenation (VA-ECMO) followed by patch repair
and implantation of a durable left ventricular assist device (LVAD).
PMID- 27501509
TI - Electrochemical Characterization of Ultrathin Cross-Linked Metal Nanoparticle
Films.
AB - Here we report the preparation, characterization, and electrochemical study of
conductive, ultrathin films of cross-linked metal nanoparticles (NPs). Nanoporous
films ranging from 40 to 200 nm in thickness composed of gold and platinum NPs of
~5 nm were fabricated via a powerful layer-by-layer spin coating process. This
process allows preparation of uniform NP films as large as 2 * 2 cm(2) with
precise control over thickness, structure, and electrochemical and
electrocatalytic properties. Gold, platinum, and bimetallic NP films were
fabricated and characterized using cyclic voltammetry, scanning electron
microscopy, and conductance measurements. Their electrocatalytic activity toward
the oxygen reduction reaction (ORR) was investigated. Our results show that the
electrochemical activity of such NP films is initially hindered by the presence
of dense thiolate cross-linking ligands. Both electrochemical cycling and oxygen
plasma cleaning are effective means in restoring their electrochemical activity.
Gold NP films have higher electric conductivity than platinum possibly due to
more uniform film structure and closer particle-particle distance. The
electrochemical and electrocatalytic performance of platinum NP films can be
greatly enhanced by the incorporation of gold NPs. This work focuses on
electrochemical characterization of cross-linked NP films and demonstrates
several unique properties. These include quick and easy preparation, ultrathin
and uniform film thickness, tunable structure and composition, and
transferability to many other substrates.
PMID- 27501510
TI - Pharmacokinetics and pharmacodynamics of single and multiple doses of the
glucagon receptor antagonist LGD-6972 in healthy subjects and subjects with type
2 diabetes mellitus.
AB - AIM: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics
of single and multiple doses of a novel, oral glucagon receptor antagonist, LGD
6972, in healthy subjects and subjects with type 2 diabetes (T2DM). METHODS: In
the single ascending dose study, LGD-6972 (2-480 mg) was administered to healthy
subjects (n = 48) and T2DM subjects (n = 8). In the multiple ascending dose
study, healthy subjects (n = 12) received a dose of 15 mg LGD-6972 and T2DM
subjects (n = 36) received doses of 5, 10 or 15 mg of LGD-6972 daily for 14 days.
RESULTS: LGD-6972 had linear plasma pharmacokinetics consistent with once-daily
dosing that was comparable in healthy and T2DM subjects. Dose-dependent decreases
in fasting plasma glucose were observed in all groups with a maximum of 3.15
mmol/L (56.8 mg/dL) on day 14 in T2DM subjects. LGD-6972 also reduced plasma
glucose in the postprandial state. Dose-dependent increases in fasting plasma
glucagon were observed, but glucagon levels decreased and insulin levels
increased after an oral glucose load in T2DM subjects. LGD-6972 was well
tolerated at the doses tested without dose-related or clinically meaningful
changes in clinical laboratory parameters. No subject experienced hypoglycaemia.
CONCLUSION: Inhibition of glucagon action by LGD-6972 was associated with
decreases in glucose in both healthy and T2DM subjects, the magnitude of which
was sufficient to predict improvement in glycaemic control with longer treatment
duration in T2DM patients. The safety and pharmacological profile of LGD-6972
after 14 days of dosing supports continued clinical development.
PMID- 27501511
TI - Preparation and application of a coated-fiber needle extraction device.
AB - In this study, a needle-trap device with fibers coated with a molecularly
imprinted polymer was developed for separation. A number of heat-resistant Zylon
filaments were longitudinally packed into a glass capillary, followed by coating
with a molecularly imprinted polymer. Then, the molecularly imprinted polymer
coating was copolymerized and anchored onto the surface of the fibers. The bundle
of synthetic fibers coated with the molecularly imprinted polymer was packed into
a 21G stainless-steel needle and served as an extraction medium. The coated-fiber
needle extraction device was used to extract volatile organic compounds from
paints and gasoline effectively. Subsequently, the extracted volatile organic
compounds were analyzed by gas chromatography. Calibration curves of gaseous
benzene, toluene, ethylbenzene, and o-xylene in the concentration range of 1-250
MUg/L were obtained to evaluate the method, acceptable linearity was attended
with correlation coefficients above 0.998. The limit of detection of benzene,
toluene, ethylbenzene, and o-xylene was 11-20 ng/L using the coated-fiber needle
trap device. The relative standard deviation of needle-to-needle repeatability
was less than 8% with an extraction time of 20 min. The loss rates after storage
for 3 and 7 days at room temperature were less than 30%.
PMID- 27501512
TI - Thymomectomy in early stage thymomas-case closed?
PMID- 27501513
TI - Removal of Ozone by Carbon Nanotubes/Quartz Fiber Film.
AB - Ozone is recognized as a harmful gaseous pollutant, which can lead to severe
human health problems. In this study, carbon nanotubes (CNTs) were tested as a
new approach for ozone removal. The CNTs/quartz fiber film was fabricated through
growth of CNTs upon pure quartz fiber using chemical vapor deposition method.
Ozone conversion efficiency of the CNTs/quartz fiber film was tested for 10 h and
compared with that of quartz film, activated carbon (AC), and a potassium iodide
(KI) solution under the same conditions. The pressure resistance of these
materials under different airflow rates was also measured. The results showed
that the CNTs/quartz fiber film had better ozone conversion efficiency but also
higher pressure resistance than AC and the KI solution of the same weight. The
ozone removal performance of the CNTs/quartz fiber film was comparable with AC at
20 times more weight. The CNTs played a dominant role in ozone removal by the
CNTs/quartz fiber film. Its high ozone conversion efficiency, lightweight and
free-standing properties make the CNTs/quartz fiber film applicable to ozone
removal. Further investigation should be focused on reducing pressure resistance
and studying the CNT mechanism for removing ozone.
PMID- 27501514
TI - Interleukin-32 levels in gingival crevicular fluid and saliva of patients with
chronic periodontitis after periodontal treatment.
AB - BACKGROUND AND OBJECTIVE: The cytokine, interleukin (IL)-32, is a relatively new
discovery. However, it is very powerful for stimulating tumor necrosis factor
alpha (TNF-alpha) under inflammatory conditions. The objective of this research
was to explore fluctuations in the levels of TNF-alpha, IL-32 and IL-10, in both
saliva and gingival crevicular fluid. The focus was on measurements taken before
and after clinical treatment of chronic periodontitis. MATERIAL AND METHODS: For
the purposes of the study, a total of 27 patients with chronic periodontitis and
27 controls (periodontally healthy) were recruited. Important clinical
periodontal criteria were established before and 4 wk after the start of the
research. The chronic periodontitis group was given an initial form of
periodontal care. Samples of saliva and gingival crevicular fluid were collected
exactly 4 wk preceding and 4 wk following the care. The levels of IL-10, IL-32
and TNF-alpha present in saliva and gingival crevicular fluid were recorded via
the use of an ELISA. RESULTS: At baseline, the levels of TNF-alpha and IL-32 in
the gingival crevicular fluid and saliva were significantly higher among patients
in the chronic periodontitis group than among patients in the control group (p <
0.05). On the other hand, at baseline the levels of IL-10 were significantly
lower in the gingival crevicular fluid and saliva of the chronic periodontitis
group than the control group (p < 0.05). A significantly positive link was found
between the TNF-alpha and IL-32 levels in the two study groups (p < 0.05). After
treatment, the levels of TNF-alpha and IL-32 in saliva and gingival crevicular
fluid were significantly lower in the chronic periodontitis group when compared
with the baseline readings. However, the levels of IL-10 were significantly
higher (p < 0.05). CONCLUSION: Ultimately, the level of IL-32 present in saliva
and gingival crevicular fluid might be useful as an indicator of the condition
and the expectations for its treatment and care. According to the results of the
research, the proinflammatory impact of IL-32 could potentially be linked to the
intensity and progression of periodontitis.
PMID- 27501515
TI - BOLD quantified renal pO2 is sensitive to pharmacological challenges in rats.
AB - PURPOSE: Blood oxygen level-dependent (BOLD) MRI has been effectively used to
monitor changes in renal oxygenation. However, R2* (or T2*) is not specific to
blood oxygenation and is dependent on other factors. This study investigates the
use of a statistical model that takes these factors into account and maps BOLD
MRI measurements to blood pO2. METHODS: Spin echo and gradient echo images were
obtained in six Sprague-Dawley rats and R2 and R2* maps were computed.
Measurements were made at baseline, post-nitric oxide synthase inhibitor (L
NAME), and post-furosemide administration. A simulation of each region was
performed to map R2' (computed as R2*-R2) to blood pO2. RESULTS: At baseline,
blood pO2 in the outer medulla was 30.5 +/- 1.2 mmHg and 51.9 +/- 5.2 mmHg in the
cortex, in agreement with previous invasive studies. Blood pO2 was found to
decrease within the outer medulla following L-NAME (P < 0.05) and increase after
furosemide (P < 0.05). Blood pO2 in the cortex increased following furosemide (P
< 0.05). CONCLUSIONS: Model-derived blood pO2 is sensitive to pharmacological
challenges, and baseline pO2 is comparable to literature values. Reporting pO2
instead of R2* could lead to a greater clinical impact of renal BOLD MRI and
facilitate the identification of hypoxic regions. Magn Reson Med 78:297-302,
2017. (c) 2016 International Society for Magnetic Resonance in Medicine.
PMID- 27501516
TI - Beyond the Billboard: The Facebook-Based Application, Donor, and Its Guided
Approach to Facilitating Living Organ Donation.
AB - Living donor solicitation can raise ethical concerns, regardless of the medium
used: newspaper, television, pulpit, billboard or Internet. Moving the search for
a living donor into the social media realm introduces the risk of unguided and
coercive patient narratives as well as decoupling or even total absence of
information that could aid the consent process. The Facebook application (app)
for living donors, called Donor (restricted to patient use), aims to address
these concerns in several ways: (i) by directing the patient's initial appeal to
friends and family; (ii) by guiding the patient's narrative; and (iii) by
providing a library of clinical, ethical and regulatory information that informs
the consent process. In this paper, we explored these features and contrasted
them with billboard solicitation activities and current independent social media
efforts. We concluded that the proactive ethical design of the Donor app is a
permissible way to help satisfy the shortfall of deceased donor livers and
kidneys.
PMID- 27501518
TI - Pyrethroid resistance is associated with a kdr-type mutation (L1014F) in the
potato tuber moth Tecia solanivora.
AB - BACKGROUND: The Guatemalan potato tuber moth, Tecia solanivora, has been the most
important pest species in Hispanico-American potato fields since its first record
on potatoes in 1956 in Guatemala. This insect pest has been spreading to other
parts of the world, including the Canary Islands in Europe. Tuber moth control
relies heavily on the use of insecticides, including pyrethroids. Here, we
assessed the likelihood of control failures and performed concentration-response
bioassays in five Colombian strains of T. solanivora to evaluate their
susceptibilities to the pyrethroid permethrin. RESULTS: Evidence of control
failures was observed in four strains tested, which exhibited moderate resistance
levels (i.e. ranging from 5.4- to 24.4-fold). However, no spatial dependence was
observed between the permethrin LC50 values and the geographic distances among
the tuber moth strains. In order to evaluate whether permethrin resistance was
mediated by potential mutations in the para-type sodium channels of T.
solanivora, the IIS4-IIS6 region of the para gene was PCR amplified and sequenced
from the five strains tested. As demonstrated across a range of different
arthropod species that exhibited knockdown resistance (kdr), we observed a single
point substitution (L1014F) at high frequencies in the para gene of all four
resistant strains. CONCLUSION: This is the first identification of a target-site
alteration-based resistance in the Guatemalan potato tuber moth T. solanivora,
which is widespread and exhibits high frequencies among geographically distant
strains, indicating that pyrethroids are probably becoming ineffective for the
control of this pest species. (c) 2016 Society of Chemical Industry.
PMID- 27501517
TI - Invasive species' leaf traits and dissimilarity from natives shape their impact
on nitrogen cycling: a meta-analysis.
AB - Many exotic species have little apparent impact on ecosystem processes, whereas
others have dramatic consequences for human and ecosystem health. There is
growing evidence that invasions foster eutrophication. We need to identify
species that are harmful and systems that are vulnerable to anticipate these
consequences. Species' traits may provide the necessary insights. We conducted a
global meta-analysis to determine whether plant leaf and litter functional
traits, and particularly leaf and litter nitrogen (N) content and carbon:
nitrogen (C : N) ratio, explain variation in invasive species' impacts on soil N
cycling. Dissimilarity in leaf and litter traits among invaded and noninvaded
plant communities control the magnitude and direction of invasion impacts on N
cycling. Invasions that caused the greatest increases in soil inorganic N and
mineralization rates had a much greater litter N content and lower litter C : N
in the invaded than the reference community. Trait dissimilarities were better
predictors than the trait values of invasive species alone. Quantifying baseline
community tissue traits, in addition to those of the invasive species, is
critical to understanding the impacts of invasion on soil N cycling.
PMID- 27501519
TI - Putative RopGAPs impact division plane selection and interact with kinesin-12
POK1.
AB - Cell shape is defined by the surrounding cell walls in plants. Thus, spatial
control over cell division planes and cell expansion polarity are essential to
maintain cell morphology. In eukaryotes, cell polarity and expansion are
controlled by Rho GTPase signalling, regulating cytoskeletal reorganization and
vesicle trafficking(1). However, until now, Rho signalling was not implicated in
mitotic events in plants. Here, we report a pair of putative Rho GTPase
activating proteins (RhoGAPs) that interact with the mitosis-specific kinesin-12
POK1, a core component of the cortical division zone/site (CDZ/CDS) that is
required for division plane maintenance in Arabidopsis(2-4). The designated
pleckstrin homology GAPs (PHGAPs) are cytoplasmic and plasma membrane associated
in interphase, but during mitosis they additionally localize to the CDZ/CDS in a
POK-dependent manner. In contrast to pok1 pok2 mutants, phgap1 phgap2 double
mutants show moderate cell wall positioning defects as a consequence of
inaccurate positioning of the cortical division zone marker POK1. We conclude
that loss of PHGAP function interferes with division plane selection in
proliferative cell divisions.
PMID- 27501520
TI - Assessment of endothelial damage and cardiac injury in a mouse model mimicking
thrombotic thrombocytopenic purpura.
AB - : Essentials Endothelial injury is thought to be a key event in thrombotic
thrombocytopenic purpura (TTP). Endothelial and cardiac damages were assessed in
a model of TTP using ADAMTS-13 knockout mice. Damages of cardiac perfusion and
function were associated with nitric oxide pathway alteration. Endothelial
dysfunction constitutes a critical event in TTP development and cardiac injury.
SUMMARY: Background Cardiac alterations represent a major cause of mortality in
patients with thrombotic thrombocytopenic purpura (TTP). Endothelial injury
remains poorly defined, but seems to be a key initiating event leading to the
formation of platelet-rich thrombi in TTP patients. Objectives To assess the
changes in endothelial function and the induced cardiac damage in a mouse model
of TTP. Patients/methods We used an animal model in which TTP-like symptoms are
triggered by injection of 2000 units kg-1 of recombinant von Willebrand factor in
ADAMTS-13 knockout mice. Results These mice developed TTP-like symptoms, i.e.
severe thrombocytopenia, schistocytosis, and anemia. On day 2, magnetic resonance
imaging demonstrated a decrease in left ventricular perfusion associated with
alteration of left ventricular ejection fraction, fractional shortening, and
cardiac output, suggesting early systolic dysfunction. This was associated with
decrease in endothelium-mediated relaxation responses to acetylcholine in
mesenteric and coronary arteries, demonstrating severe early endothelial
dysfunction. In parallel, we showed decreased cardiac expression of endothelial
nitric oxide (NO) synthase and increased expression of antioxidant enzymes,
suggesting alteration of the NO pathway. At this time, cardiac
immunohistochemistry revealed an increase in the expression of VCAM-1 and E
selectin. Conclusion This study provides evidence that the heart is a sensitive
target organ in TTP, and shows, for the first time, strong mesenteric and
coronary endothelial dysfunction in an induced-TTP model. The mechanisms
incriminated are the occurrence of a pro-oxidant state, and proadhesive and
proinflammatory phenotypes. This previously largely unrecognized vascular
dysfunction may represent an important contributor to the systemic organ failure
occurring in TTP.
PMID- 27501521
TI - Analysis of biophysical and functional consequences of tropomyosin-fluorescent
protein fusions.
AB - The dynamic nature of actin polymers is modulated to facilitate a diverse range
of cellular processes. These dynamic properties are determined by different
isoforms of tropomyosin which are recruited to distinct subpopulations of actin
polymers to differentially regulate their functional properties. This makes
tropomyosin an attractive target for labelling discrete actin populations. We
have assessed the effect of different fluorescent labelling strategies for this
protein. Although tropomyosin-fluorescent fusions decorate actin in vivo, they
are either nonfunctional or perturb regulation of actin nucleation and cell cycle
timings. Thus, conclusions and physiological relevance should be carefully
evaluated when using tropomyosin fusions.
PMID- 27501522
TI - Measuring glycated haemoglobin in women with gestational diabetes mellitus: How
useful is it?
AB - BACKGROUND: Glycated haemoglobin (HbA1c) is an important tool for assessing
glycaemic status in patients with diabetes, but its usefulness in gestational
diabetes mellitus (GDM), is unclear. AIMS: The aim of this study is to evaluate
whether HbA1c in women with GDM is valuable in predicting adverse pregnancy
outcomes. MATERIALS AND METHODS: A retrospective review of women with GDM who had
HbA1c measured at diagnosis of GDM (GHb-diag) and at 36 weeks gestation (GHb-36
weeks) was conducted. The association between HbA1c and various pregnancy
outcomes was assessed RESULTS: Among 1244 women with GDM in our cohort, both GHb
diag and GHb-36 weeks were independent predictors for large-for-gestation (LGA)
babies (OR 1.06, P = 0.005 and OR 1.06, P = 0.002, respectively) and neonatal
hypoglycaemia (OR 1.10, P < 0.001 and OR 1.09, P < 0.001, respectively). Women
with HbA1c >= 5.4% (35 mmol/mol) at diagnosis had significantly greater risk for
LGA (15.3% vs 8.2%, P < 0.001) and neonatal hypoglycaemia (42.2% vs 23.6%, P <
0.001) than those below this cut-off. The difference between GHb-diag and GHb-36
weeks was small and improvement in HbA1c by 36 weeks was not associated with
better pregnancy outcomes. CONCLUSION: We showed that measurement of HbA1c,
either at the time of diagnosis of GDM or toward the end of pregnancy, were both
associated with adverse pregnancy outcomes. Women with elevated HbA1c (>5.4% or
35 mmol/mol) at diagnosis of GDM should be monitored closely during pregnancy.
However, there is not enough evidence to suggest that repeating HbA1c toward the
end of pregnancy will provide additional information in predicting adverse
pregnancy outcomes.
PMID- 27501523
TI - Cytoplasmic expression of beta-catenin is an independent predictor of progression
of conventional renal cell carcinoma: a simple immunostaining score.
AB - AIMS: The aims of this study were to investigate the potential of beta-catenin as
a biomarker for predicting cancer-specific survival, and to find a reproducible
mode of evaluation of immunohistochemistry. METHODS AND RESULTS: beta-Catenin
expression was analysed by immunohistochemistry in a cohort of 488 patients with
conventional renal cell carcinoma (RCC) operated on between 2000 and 2010. The
association between beta-catenin expression and cancer-specific survival was
assessed with univariate and multivariate Cox regression models in relation to
conventional clinical pathological prognostic factors, and by Kaplan-Meier
survival analysis with the log rank test. The univariate Cox regression model
revealed an association of cytoplasmic beta-catenin positivity and pathological
variables with cancer-specific death. The multivariate Cox regression model
analysis of tumours without metastatic disease at the first presentation
identified the T-classification (P < 0.001) and cytoplasmic beta-catenin
positivity as risk factors for postoperative tumour progression. Specifically,
cytoplasmic beta-catenin expression was an independent factor indicating an
unfavourable prognosis, with a four-fold higher risk of cancer-specific death
(relative risk 4.017; 95% confidence interval 2.489-6.482; P < 0.001). The median
survival time for patients with tumours showing cytoplasmic accumulation of beta
catenin was 48 months, whereas the overall survival time was 166 months.
CONCLUSIONS: Cytoplasmic beta-catenin expression is an independent prognostic
factor for conventional RCC, and may help to identify patients with a high risk
of cancer-specific death and to direct optimized active surveillance or adjuvant
therapy.
PMID- 27501524
TI - Physicians' identification of the need for palliative care in people with
intellectual disabilities.
AB - BACKGROUND: A growing number of people with intellectual disabilities (ID) is
suffering from life-threatening chronic illnesses and is therefore in need for
palliative care. AIMS: We aimed to explore how the need for palliative care is
recognized in people with ID. METHODS AND PROCEDURES: We conducted a semi
structured interview study among 10 ID-physicians in the Netherlands. OUTCOMES
AND RESULTS: Identification of people with ID in need for palliative care mostly
results from a process in which multiple signals from different information
sources converge and lead to a growing awareness. As a result, ID-physicians do
not expect people to return to their prior level of health or functioning, but
rather expect an irreversible decline leading to death. The presence, stage and
prognosis of the disease, physician-patient interaction, and communication with
proxies who provide contextual information are factors influencing the process.
CONCLUSIONS AND IMPLICATIONS: Distinctive for a population of people with ID are
the frequent diagnostic uncertainty in people with ID, the patients'
communicational abilities and the reliance of ID-physicians on close proxies. We
argue for a proactive attitude of physicians regarding care and support of people
with ID with palliative care needs.
PMID- 27501525
TI - Progress and challenges in diagnosis of dysferlinopathy.
AB - Dysferlin-deficient limb girdle muscular dystrophy type 2B, distal Miyoshi
myopathy, and other less frequent phenotypes are a group of recessive disorders
called dysferlinopathies. They are characterized by wide clinical heterogeneity.
To diagnose dysferlinopathy, a clinical neuromuscular workup, including
electrophysiological and muscle imaging investigations, is essential to support
subsequent laboratory testing. Increased serum creatine kinase levels, distal or
proximal muscle weakness, and myalgia with onset in the second or third decades
are the main clinical features of the disease. In muscle biopsies, severe
dysferlin deficiency by immunoblot or its abnormal localization by
immunohistochemistry are the gold standard, as they have a high diagnostic value.
Dysferlin testing on monocytes is a valuable alternative to muscle
immunoblotting. Molecular techniques for gene mutation detection, such as next
generation sequencing, have improved the genetic diagnosis, which is crucial for
treatment and genetic counselling. Muscle Nerve 54: 821-835, 2016.
PMID- 27501526
TI - High plasticity reversible resistive switching in heteroepitaxial metal/CeO2-x
/Nb:SrTiO3/Ti/Pt structures.
AB - We report on the characterization of resistive switching devices based on
epitaxial CeO2 thin films as a functional material. CeO2 epitaxial thin films
were grown by the pulsed laser deposition technique on conductive substrates.
Platinum and titanium nitride top electrodes (TE) were successively deposited.
Very good performances, in terms of resistivity switching and multilevel
operation capability, were obtained using the Pt TE. The dependence of the low
resistance and high resistance state on the TE material and on the CeO2 film
thickness were explained. The electrical characteristics of these
heterostructures make them promising as synapse for neuromorphic computation, but
suggest also their use with multi-valued digital systems or multibit memory
cells.
PMID- 27501527
TI - Complex effects of dyslexia risk factors account for ADHD traits: evidence from
two independent samples.
AB - BACKGROUND: Developmental dyslexia (DD) and attention deficit/hyperactivity
disorder (ADHD) are among the most common neurodevelopmental disorders, whose
etiology involves multiple risk factors. DD and ADHD co-occur in the same
individuals much more often than would be expected by chance. Several studies
have found significant bivariate heritability, and specific genes associated with
either DD or ADHD have been investigated for association in the other disorder.
Moreover, there are likely to be gene-by-gene and gene-by-environment interaction
effects (G * G and G * E, respectively) underlying the comorbidity between DD and
ADHD. We investigated the pleiotropic effects of 19 SNPs spanning five DD genes
(DYX1C1, DCDC2, KIAA0319, ROBO1, and GRIN2B) and seven DD environmental factors
(smoke, miscarriage, birth weight, breastfeeding, parental age, socioeconomic
status, and parental education) for main, either (a) genetic or (b)
environmental, (c) G * G, and (d) G * E upon inattention and
hyperactivity/impulsivity. We then attempted replication of these findings in an
independent twin cohort. METHODS: Marker-trait association was analyzed by
implementing the Quantitative Transmission Disequilibrium Test (QTDT).
Environmental associations were tested by partial correlations. G * G were
investigated by a general linear model equation and a family-based association
test. G * E were analyzed through a general test for G * E in sib pair-based
association analysis of quantitative traits. RESULTS: DCDC2-rs793862 was
associated with hyperactivity/impulsivity via G * G (KIAA0319) and G * E
(miscarriage). Smoke was significantly correlated with hyperactivity/impulsivity.
We replicated the DCDC2 * KIAA0319 interaction upon hyperactivity/impulsivity in
the twin cohort. CONCLUSIONS: DD genetic (DCDC2) and environmental factors (smoke
and miscarriage) underlie ADHD traits supporting a potential pleiotropic effect.
PMID- 27501528
TI - Successful multivessel percutaneous coronary intervention for acute coronary
syndrome in a HIV-positive severe haemophiliac.
PMID- 27501529
TI - The two sides of creatinine: both as bad as each other?
PMID- 27501530
TI - Development and pilot testing of an educational intervention for parents,
caregivers and teachers of children with verbal communication disabilities in
Mexico.
AB - The purpose of this study was to implement and test an educational intervention
aimed at training parents/caregivers and teachers in strategies to support
children with verbal communication disabilities (VCDs). We carried out a
descriptive observational research conducted in two phases during 2013-2014: a
mixed-method diagnosis and intervention development. We used convenience sampling
to select the parents/caregivers and teachers of first-to-third graders with VCDs
across four public elementary schools in a suburban community in central Mexico.
Diagnosis was based on questionnaires conducted with parents/caregivers (n = 38)
and teachers (n = 16). The instruments focused not only on the respondents'
socioeconomic characteristics and general knowledge about VCDs but also included
open questions (24/42) about their common practices and support for children with
VCDs. The intervention was built on data collected through the questionnaires,
and was designed according to the Integral Intervention Model framework based on
the ecosystemic approach. Participants were parents/caregivers and teachers of
children with VCDs. Main results showed that the participants were trained in
various support techniques, they gained knowledge about VCDs and changed their
perception of their own ability to help children with language impairments. As an
important upshot of the intervention, communication and networking among
parents/caregivers and teachers increased. The main strengths of this research
reside in its solid theoretical foundation and the fact that intervention design
was based on the specific needs of the target group. In as much as the public
health problem of VCDs in Mexico has barely been studied and has received minimal
official support, it is essential to engage additional social actors,
stakeholders and decision-makers in the implementation of permanent actions. Our
study emphasises the importance of recognising this form of health impairment as
a social responsibility and not as an individual family problem.
PMID- 27501531
TI - The remaining core: a fresh look at religiosity trends in Great Britain.
AB - In recent years, there has been a growing argument that the end product of
secularization may not be a disappearance of all things religious, but rather a
polarization between a larger secular group in society and smaller religiously
fervent and active communities. Yet, there has been little empirical testing of
this theory in contexts of advanced secularization. The aim of this paper is to
fill this gap by studying individual belief and religiosity trends over the past
four decades in Great Britain, searching specifically for evidence of the
population splitting more and more between religious 'nones' removed from all
forms of religion, and actively religious individuals characterized by strong
beliefs and favourable to the public involvement of religion. Analysing
descriptive statistics from the 1983-2012 BSAs as well as more detailed models
from the 1991, 1998 and 2008 BSAs, we find growing differences in levels of
beliefs and attitudes towards public religion between the increasing proportions
of unaffiliated and, in recent years and among younger cohorts, more stable
proportions of religiously committed individuals. The remaining religiously
committed generally have stronger beliefs and more favourable views towards
religious leaders influencing politics in 2008 compared with 1991, and the
unaffiliated, less favourable views towards public religion.
PMID- 27501532
TI - Effect of auriculopalpebral nerve block on Schirmer tear test I values in normal
horses.
AB - OBJECTIVE: To compare Schirmer tear test I (STTI) values collected in normal
horses with and without an auriculopalpebral nerve block. PROCEDURE: Schirmer
tear test I values were measured in 20 clinically normal horses (38 eyes) with a
median age of 12 years. The order of eyes tested was randomized. Within 24-48 h,
at the same time of day, tear measurements were collected again after
administration of an auriculopalpebral nerve block. Each block was performed a
minimum of 5 min prior to each STT I. A repeated-measures model was used to
analyze differences between STT I values in eyes with and without nerve blocks
incorporating within horse correlation between eyes. The mixed-model included
fixed factors of treatment and eye and a random intercept for each horse. An
unstructured covariance structure was used. RESULTS: On average, STT I values
measured in eyes after auriculopalpebral nerve blocks were 0.55 mm/min greater
than those without nerve blocks. This difference was not statistically
significant (P = 0.5268). CONCLUSIONS: There was no effect of auriculopalpebral
nerve block on STT I values in normal horses.
PMID- 27501533
TI - Considerations about the Aspirin and Tranexamic Acid for Coronary Artery Surgery
(ATACAS) trial.
PMID- 27501534
TI - Antihypertensive agents and arterial stiffness.
PMID- 27501535
TI - Cryomicroscopy provides structural snapshots of influenza virus membrane fusion.
AB - The lipid-enveloped influenza virus enters host cells during infection by binding
cell-surface receptors and, after receptor-mediated endocytosis, fusing with the
membrane of the endosome and delivering the viral genome and transcription
machinery into the host cell. These events are mediated by the hemagglutinin (HA)
surface glycoprotein. At the low pH of the endosome, an irreversible
conformational change in the HA, including the exposure of the hydrophobic fusion
peptide, activates membrane fusion. Here we used electron cryomicroscopy and
cryotomography to image the fusion of influenza virus with target membranes at
low pH. We visualized structural intermediates of HA and their interactions with
membranes during the course of membrane fusion as well as ultrastructural changes
in the virus that accompany membrane fusion. Our observations are relevant to a
wide range of protein-mediated membrane-fusion processes and demonstrate how
dynamic membrane events may be studied by cryomicroscopy.
PMID- 27501537
TI - FALL-RELATED ACTIVITIES OF DAILY LIVING AND BEHAVIOUR DISTURBANCES IN DEMENTIA.
AB - The purpose of this study is to clarify the activities of daily living and
behaviour disturbances related to inpatients and outpatients with dementia
experiencing falls. Patients diagnosed with dementia belonging to 18 facilities
which consented to the study were subjected. The study involved "whether or not
the patient has fallen in the past 12 months", "Barthel Index (B.I)", and
"Dementia Behaviour Disturbance Scale (DBD)" and other data from 325 people in 18
facilities who had been diagnosed with dementia. The ratio of subjects who had
fallen to those who had not was 113:212. The results of multiple logistic
regression analysis showed that the study items related to falls including the
DBD item of "making unwarranted accusations" had an OR = 1.445, 95% CI (1.133
1.843), the DBD item of "refusing to eat" had an OR = 0.699, 95% CI (0.521-
0.938), the B.I item of "feeding" had OR = 1.115, 95% CI (1.032-1.204) and the
B.I item of "bathing" had OR = 0.782, 95% CI (0.671-0.912). Integral
characteristics of dementia patients who have fallen are assumed to be making
unwarranted accusations, having a low rate of refusing to eat, being able to eat
alone and requiring attention when bathing.
PMID- 27501536
TI - One-way membrane trafficking of SOS in receptor-triggered Ras activation.
AB - SOS is a key activator of the small GTPase Ras. In cells, SOS-Ras signaling is
thought to be initiated predominantly by membrane recruitment of SOS via the
adaptor Grb2 and balanced by rapidly reversible Grb2-SOS binding kinetics.
However, SOS has multiple protein and lipid interactions that provide linkage to
the membrane. In reconstituted-membrane experiments, these Grb2-independent
interactions were sufficient to retain human SOS on the membrane for many
minutes, during which a single SOS molecule could processively activate thousands
of Ras molecules. These observations raised questions concerning how receptors
maintain control of SOS in cells and how membrane-recruited SOS is ultimately
released. We addressed these questions in quantitative assays of reconstituted
SOS-deficient chicken B-cell signaling systems combined with single-molecule
measurements in supported membranes. These studies revealed an essentially one
way trafficking process in which membrane-recruited SOS remains trapped on the
membrane and continuously activates Ras until being actively removed via
endocytosis.
PMID- 27501538
TI - PHYSIOLOGICAL STRAIN AMONG WOMEN POTATO CULTIVATORS IN WEST BENGAL, INDIA.
AB - The present study was aimed to evaluate physiological strain among women
cultivators engaged in potato cultivation. The cross-sectional descriptive study
was conducted on 150 women participants in different districts of West Bengal
State, India. The physiological strain was evaluated by working heart rate, blood
lactate and oxygen consumption. The average working heart rate was 109.97 +/-
9.94 beats/min when all tasks were considered together. According to the working
heart rate, oxygen consumption and energy cost, the potato cultivation job was
categorized as a moderate work category. Whereas, according to cardiovascular
stress index (CSI), all tasks of potato cultivation were categorized into a
stressful category. The more experienced workers were more productive than their
less experienced counterparts, and this increased productivity appeared to be a
combination of greater efficiency and greater physical exertion. Stepwise
multiple linear regression analyses revealed that work pace and work experience
had significant association with all the indices of physiological strain. Work
pace had strongest significant impact on these indices even after controlling the
effect of age, work experience and efficiency. It was concluded that during
performing potato cultivation tasks the workers had a great extent of
physiological strain.
PMID- 27501539
TI - PULMONARY FUNCTION STUDIES IN FEMALE SINGERS OF KOLKATA, INDIA.
AB - Singing performance is based on the efficiency of the respiratory system. The
present study was aimed to evaluate the results of pulmonary function tests
(PFTs) in female singers of Kolkata, India and to compare the data with their
sedentary counterparts from India and abroad. The study was also aimed to propose
prediction norms for PFTs in both the groups. Fifty-six female singers and fifty
two female non-singers (control group) with similar socioeconomic backgrounds
were randomly sampled from the Rabindrabharati University, Kolkata. Pulmonary
function tests were conducted by an Expirograph and the peak expiratory flow rate
(PEFR) was measured by Wright's peak flow meter. PFTs were significantly higher
in singers than in their control group. The correlation matrix depicted a
significant relationship of physical parameters (age, body height and body
weight) with vital capacity (VC), forced vital capacity (FVC), forced expiratoty
volume in 1 second (FEV1) and PEFR in both groups. Regression equations were
computed to predict PFTs from physical parameters and duration of invovlement in
singing training. The results indicated that female singers of Kolkata had higher
lung capacity than their non-singer counterparts probably because of their
regular practice and training of singing that required imperative effort of the
respiratory system.
PMID- 27501540
TI - SEX DIFFERENCES IN THE EFFECTS OF DIVERSE SOUNDS ON HEART RATE VARIABILITY.
AB - With the goal of facilitating the creation of relaxing sound environments in
stressful places, such as offices, we examined differences in the heart rate
fluctuations of men and women induced by different sounds. Twenty-three healthy
students (13 males and 10 females) aged between 18 and 23 listened to seven
different sounds while we collected electrocardiogram data. We extracted the high
frequency component (HF) and low frequency component (LF) of the signals using
the wavelet method, and calculated LF/HF. We found no statistically significant
differences between males and females in the frequency distribution of a no
change group, increased group, and decreased group for any sound. However,
certain sounds had somewhat similar patterns for men and women for all three
groups. Additionally, the pairs of experimental sounds with highly similar
effects on individuals were different for men and women.
PMID- 27501541
TI - [Editorial].
PMID- 27501542
TI - [Prof. Dr. Gunnar Stollberg. 1 October 1945 Berlin, 25 March 2014 Berlin].
PMID- 27501543
TI - [Main topic: Patient history in hospital, sanatorium and hospital].
PMID- 27501544
TI - [An interest group in the Haina Hospital against the anatomic dissection. Actors
and their protest readiness against organizational expectations].
AB - Between 1839 and 1853 several petitions have been addressed by inmates of the
Haina hospital (Hesse, Germany) in order to save them from being transferred to
the Anatomical Institute of the University of Marburg for post mortem dissection.
In 1855, exemptions were granted in certain cases. Initially, the petitioners'
strategies of argumentation and procedure have been analysed; then--referring to
the application being sent in December 1847 and signed by 30 persons--the focus
goes to the formation of this group and their opportunities for action. As a
result it can be stated that inmates being physically ill or impaired or with
impeded visual sensory perception tried to withstand unsuitable restrictions of
their liberty of action as well as their personal rights induced by the routines
of every-day hospital life. Guiltless for depending on public assistance they
were not willing to accept unjustified curtailing of their personal and moral
integrity. The attempts of being saved from anatomical dissection are part of the
inmates' self-assertion.
PMID- 27501545
TI - [Private charity - public health service. Comparison between British and German
birthing centers of the 18th century].
AB - In the eighteenth century, lying-in hospitals were founded in many European towns
and cities. The way in which these institutions were financed differed greatly
across Europe. In the UK, most of them were "charities" and relied on donations
from wealthy benefactors, whereas on the continent they were usually funded by
"public" money, be it from the state or local communities. The paper focuses on
British charities and German hospitals, and explores the corollaries of the mode
of financing. In the eighteenth century, a market emerged in Britain where
numerous charities with different aims competed for donations from the well-to
do. For attracting benefactors, a charity had to convince potential donors that
its clientele and purpose were particularly deserving, and that it used the money
donated in a cost-efficient way. In Germany, it was mainly bureaucrats and
governments who had to be persuaded, but public opinion did matter as well. In
British lying-in charities, the main donors acted as governors, and benefactors
could recommend persons for being admitted. In publicly funded German hospitals,
the medical directors had much more power. In the competitive market, in which
British charities acted, out-patient dispensaries (policlinics) became
increasingly important, since they could argue that they were more cost-efficient
and had lower mortality. In Germany, however, hospitals remained the dominant
type of assistance in this field, in spite of the criticism they received. The
different sources of finance appear to have been one of the reasons for this
divergence. Teaching was the main purpose of most German lying-in hospitals. They
either trained medical students or midwife apprentices or both. Since the
patients served as teaching objects, all women were welcomed, and in fact most
patients were single mothers. By contrast, most of the British institutions
admitted only married women, because donors did not wish to encourage immorality.
The charities staged the relation between donors and patients as a personal
patron-client bond.
PMID- 27501546
TI - [Women's complaint leadership in the Causa Kleinwachter. A contribution to
patient history of the Innsbruck maternity hospital].
AB - On the basis of the Innsbruck Maternity Clinic this paper deals with the
individual and collective worlds of experience of obstetric patients. However,
not only the patient's view on the proceedings in this specific medical space is
being reconstructed, also the prevailing conventions surrounding the treatment of
pregnant, parturient and puerperal patients serving as clinical material in
obstetric research and education are critically scrutinised. At the centre of
this paper stands Dr. Ludwig Kleinwachter's period of duty, who acted as
professor for obstetrics and gynaecology in Innsbruck between 1877 and 1881.
During this period numerous conflicts regarding the treatment of patients are
documented. Concerned about the good reputation of the Maternity Clinic, the
Tyrolean State Committee, as the Clinic's provider, tried to solve the crisis.
The existing letters of complaint and protocols do not only give a voice to the
women concerned, but also to the medical professions as well as the local
political representatives involved.
PMID- 27501547
TI - [Power and everyday life in a lunatic asylum environment - a case example from
Glasgow at the beginning of the 20th century].
AB - In this article the focus of analysis lies on power relations in everyday life in
one of Glasgow's Pauper Lunatic Asylums at the turn of the twentieth century.
Taking a sample of patient case files I examine the daily processes of
negotiation between inmates and their relatives, physicians, attendants and
nurses as well as the poor law administration. Some cases especially exemplify
the complex relationships between the actors. They show which opportunities and
boundaries existed for "power brokering" for the more powerless. At the same time
these cases illustrate the formal and practical limits of enforcement by doctors
and nursing staff. Without turning a blind eve to hierarchies and power
imbalances the analysis shows that even in settings like "total institutions"
power remains volatile. Even there the more powerful actors have to actualize,
seize and prevail on a regular basis.
PMID- 27501548
TI - [Insanity, life crises and longing for a "real life". On the discussion of
deviant behavior and mental disorders in psychiatry of the 19th and 20th
century].
AB - On insanity, life crises and the longing for a "right life". A contribution to
the discussion on the deviant behavior and mental disorders in the psychiatry of
the 19th and 20th centuries using the example of patient stories. History of
psychiatry, understood as social and cultural history, provides the framework for
this micro-historical article. Using the example of three patients treated in
Wuerttemberg or Baden psychiatric asylums between 1875 and 1912, the article
focuses on the critical analysis of types of asylums, their practices of
admissions, therapies and power relations between patients and staff. Ways of
thinking and acting, subjective experiences and emotions are exemplified by
patient records, personal testimonials and contemporary publications again by
patients and staff. The article examines options of patients to influence the
institutional daily asylum routine against the background of its complexity and
dynamics. Borders, manipulations, malingering and querulous paranoia are at stake
here. Furthermore, the article reflects various forms of social interaction with
the power regulating therapeutic and disciplinary aspects against the backdrop of
the "canons of rules" of the asylum as well as the contemporary political and
legal framework.
PMID- 27501549
TI - Introduction.
PMID- 27501550
TI - Records of "Infirmity": Dis/ability and Life Writing in 16th-Century Germany.
PMID- 27501551
TI - Disablement as Disability? Public Welfare and the Disabled Poor in Early Modern
Germany.
PMID- 27501552
TI - A Life in Darkness--Coping with Blindness in Rural Society about 1800 in Hesse.
PMID- 27501553
TI - Disability in the Early Modern Society: or How to Read "Against the Grain" and
"Fill in Gaps".
PMID- 27501554
TI - [Preliminary remarks].
PMID- 27501555
TI - [Over 70 years after "Action T4": a new memorial at the site of murder of the
sick in Brandenburg/Havel].
PMID- 27501556
TI - [Artifact discoveries in Hartheim and their significance for memorial site
development].
PMID- 27501557
TI - [What means "resistance" against National Socialism "euthanasia" crime].
PMID- 27501558
TI - [Impressions and memories of the educational trip to Florence for the 19th
Symposium "The art of healing and healing art in buildings and pictures from the
9th to 12th October 2013].
PMID- 27501559
TI - [Hospital in the picture - pictures of hospitals in Italian art between 1385 and
1529].
PMID- 27501561
TI - [Hospitals in the Islamic world].
PMID- 27501560
TI - [Hospitals and patients in Tuscany during the Renaissance].
PMID- 27501562
TI - [Surgery and art].
PMID- 27501563
TI - [10 years of art in DRK Clinics Berlin/Westend - what happens next?].
PMID- 27501564
TI - [20th Symposium of the German Society for Hospital History from 10th to 12th
October 2014 in Munster (Westfalen)-- - introduction].
PMID- 27501565
TI - [An appreciation of the services of the honorary chairman Axel Hinrich Murken. 30
years chairman of the German Society of Hospital History 1979 to 2009 and editor
of the Historia Hospitalium 1972 to 2010].
PMID- 27501566
TI - [Giving the hospital a place in history. 50 years German Society of Hospital
History. A retrospect of half a century (1964 -2014)].
PMID- 27501567
TI - [Responsibilities and goals of hospital history. A personal retrospect from the
viewpoint of a hospital architect and historian].
PMID- 27501568
TI - [Organization and administration. 11 years as managing board member of the German
Society of Hospital History e. V. (2003 - 2014)].
PMID- 27501569
TI - [The Herrlinger case: a controversy of ethics in anatomy and medical history].
PMID- 27501570
TI - [Between continuity and new beginning. On the development of university medical
history in postwar Germany].
PMID- 27501571
TI - [History and responsibility: comments on the cross section field GTE (history,
theory and ethics) in the medical curriculum].
PMID- 27501572
TI - [For the poor, sick and pilgrims. Late middle ages welfare policy in the city of
Munster].
PMID- 27501573
TI - Forms of Protection for Historic Hospitals.
PMID- 27501574
TI - [The district Weinheim nursing home in national socialism].
PMID- 27501575
TI - [Success or failure? Surgical robot from the historical perspective].
PMID- 27501576
TI - [Iron bedsteads. On the history of the hospital bed (1700 - 1900)].
PMID- 27501577
TI - [The Nicolai Hospital. Study of the leprosorium in the middle ages of Luneburg
(1251-1530)].
PMID- 27501578
TI - EDITORIAL.
PMID- 27501579
TI - THE ART OF MEDICINE.
PMID- 27501580
TI - CLIMATE CHANGE AND HEALTH: A FEBRILE PLANET.
PMID- 27501581
TI - BROKEN FACES OF WAR THE QUEENS HOSPITAL, SIDCUP, 1917-1925.
PMID- 27501582
TI - HEALTH CARE IN AUSTERITY FROM THE FALKLANDS TO AFGHANISTAN AND BEYOND.
PMID- 27501583
TI - IN 2014 CAN WE PREVENT DEMENTIA?
PMID- 27501584
TI - GYNAECOLOGICAL CANCER: GREAT PROGRESS FROM MY HEROES BUT IS IT TIME FOR A
PARADIGM SHIFT?
PMID- 27501585
TI - MEDICINE, WAR AND CAPTIVITY: SOUTHEAST ASIA 1941-1945.
PMID- 27501586
TI - ON CRUSADERS ANCIENT AND MODERN THE ORDER OF ST JOHN.
PMID- 27501587
TI - LORD MORAN AND WINSTON CHURCHILL DID THE PRCP HELP TO WIN THE WAR.
PMID- 27501588
TI - BARIATRIC SURGERY--BELIEF, BIOLOGY OR BEHAVIOUR.
PMID- 27501589
TI - HISTORY DOWN THE DRAIN.
PMID- 27501590
TI - Sleepless in America: Burning the Candle at Both Ends? At What Cost?
PMID- 27501591
TI - Osteonecrosis of the Jaw in Patients Receiving Bone-Targeted Therapies: An
Overview--Part I.
AB - Urologic patients receiving bone-targeted therapies are at risk of developing
osteonecrosis of the jaw (ONJ). ONJ has historically been associated with
bisphosphonate therapy. More recently, RANK-Ligand inhibitors (denosumab) have
also been used to reduce the risk of skeletal-related events in patients who have
advanced cancers with bone metastases. More than 65% of men with metastatic
prostate cancer and nearly 75% of women with metastatic breast cancer are
affected by bone metastases. The literature has described ONJ associated with
bisphosphonate therapy as bisphosphonate-related osteonecrosis of the jaw
(BRONJ). However, with evidence also linking the use of RANK-Ligand inhibitors
with osteonecrosis of the jaw, we advocate use of the term "anti-bone resorption
therapy-related osteonecrosis of the jaw" (ABRT-ONJ). The term "medication
related osteonecrosis of the jaw" (MRONJ) is now becoming more widespread. There
is not a universally accepted definition of ABRT-ONJ, which may have hindered
recognition and reporting of the condition. In Part I of this article, a review
of current knowledge around the etiology of ABRT-ONJ and incidence data are
provided. In Part II, we provide an audit of ONJ in a nurse consultant-led bone
support clinic. In the article, we refer to zoledronic acid because this is the
bisphosphonate of choice for use in men with prostate cancer in the United
Kingdom.
PMID- 27501592
TI - Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons
Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted
Therapies for Metastatic Cancers to the Skeleton?--Part II.
AB - Men who receive bone-targeted therapy for metastatic prostate cancer are at
increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been
associated with the administration of bone-targeted therapies in association with
other risk factors. ONJ can be distressing for a patient because it can cause
pain, risk of jaw fracture, body image disturbance, difficultly eating, and
difficulty maintaining good oral hygiene. The aim of this article is to report
results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS)
before initiation of bone-targeted therapies and whether it may reduce the risk
of ONJ in patients receiving bone-targeted therapies for advanced cancers.
PMID- 27501593
TI - Cycling Versus Continuous Mode In Neuromodulator Programming: A Crossover,
Randomized, Controlled Trial.
AB - This is a randomized, controlled, blind, crossover trial comparing cycling versus
continuous programming of a sacral neuromodulator in women diagnosed with
overactive bladder (OAB). At 6 months, treatment order significantly affected
Overactive Bladder Questionnaire - Short Form (OABq-SF) symptom scores. The
cycling followed by continuous stimulation group had superior OABq-SF scores (p >
0.02).
PMID- 27501594
TI - Preoperative Nutritional Status and The Impact on Radical Cystectomy Recovery: An
International Comparative Study.
AB - In radical cystectomy, under-nutrition is common and has detrimental
physiological and clinical effects, which can lead to increased complications and
prolonged recovery. This article compares measurements and outcomes across
continents in this patient population with advanced bladder cancer. The
association of preoperative nutritional risk, nutritional status, and length of
stay is equal across continents, and the results promote increased clinical
awareness that women at severe risk should be identified preoperatively.
PMID- 27501595
TI - Decision-Making in Prostate Cancer: Active Surveillance Over Other Treatment
Options.
AB - A qualitative-descriptive study of four patients with prostate cancer used the
Cognitive-Social Health Information Processing framework to understand how and
why men diagnosed with prostate cancer choose active surveillance over other
treatment options. In accordance with the literature, it was found that the
surgeon or general practitioner's recommendation was the most influential factor
when patients are making a treatment decision.
PMID- 27501596
TI - Application to the Evidence Base: Decision-Making in Prostate Cancer: Active
Surveillance over Other Treatment Options.
PMID- 27501598
TI - Comparison of Spraying and Nebulized Lidocaine in Patients Undergoing Esophago
Gastro-Duodenoscopy: A Randomized Trial.
AB - OBJECTIVE: Esophago-gastro-duodenoscopy (EGD) was performed under the topical
anesthesia of the pharynx. However spraying lidocaine was found to be an annoying
maneuver to patients, while nebulized lidocaine appeared to efficiently suppress
gags and cough reflexes in airway anesthesia. This study aimed to compare the
effectiveness of spraying and nebulized lidocaine for patients undergoing EGD.
MATERIAL AND METHOD: A total of 110 patients undergoing elective EGD, with a
history of neither lidocaine intolerance nor irritable airways due to smoking,
chronic obstructive pulmonary disease (COPD), upper respiratory infection,
asthma, cardiac and pulmonary diseases and allergy to lidocaine were included.
All patients were randomized into two groups: A- where 5 puffs (10 mg/puff) of
spraying lidocaine were administered four times at 5-minute intervals, up to a
total dose of 200 mg, and B-where 250 mg of nebulized lidocaine was administered
via a nebulization kit with an oxygen face mask of 7 LPM for 15 minutes prior to
the commencement of EGD. The procedure was performed by the same board-certified
endoscopist The co-researcher who was blinded to the lidocaine administration
technique assessed the ease of esophageal instrumentation as either difficult,
poor; fair or excellent. Both the endoscopist and the patients expressed their
satisfaction by using the numerical rating scale. RESULTS: The endoscopist
expressed her satisfaction with instrumentation, which showed significant
difference between group A and group B as 84.8 +/- 8.3 and 79.2 +/- 11.2,
respectively. The co-researcher also found that group A patients responded to the
ease of esophageal instrumentation better than those in group B. However
nebulized lidocaine had significant advantages over spraying lidocaine, with
better acceptance in patients undergoing EGD. CONCLUSION: The endoscopist
expressed her approval of spraying lidocaine for taking less time to start the
procedure, ease for instrumentation, less gag reflex during the procedure, less
presence of hypersecretion, and smooth operation. However participants favored
nebulized lidocaine administration.
PMID- 27501597
TI - A Randomized Placebo-Controlled Trial of Oral Ramosetron for Prevention of Post
Operative Nausea and Vomiting after Intrathecal Morphine in Patients Undergoing
Gynecological Surgery.
AB - BACKGROUND: The incidence of postoperative nausea and vomiting (PONV) after
intrathecal morphine is high. Ramosetron is a 5-HT3 antagonist that has been
shown to reduce PONV in general anesthesia. The objective of this study was to
evaluate the efficacy of Ramosetron in preventing PONV MATERIAL AND METHOD: 165
patients undergoing elective gynecological surgery under spinal anesthesia were
randomly allocated to two groups: the Ramosetron group (0.1 mg orally, n = 82),
and the placebo group (oral corn starch, n = 83). The incidence of PONV severity
of nausea and use of rescue antiemetic during the first 24 hour after surgery
were evaluated. RESULTS: The incidence of PONV was significantly lower in the
Ramosetron group compared with the placebo group (24.4% vs. 44.6%, number needed
to treat (NNT) = 5.0). The severity of nausea was significantly lower in the
Ramosetron group compared with the placebo group (20.7% vs. 39.8%, NNT = 6.0) in
the 24 hour period. CONCLUSION: Oral Ramosetron 0.1 mg was more effective than
placebo in PONV prevention and reduced the incidence of moderate to severe nausea
after intrathecal morphine in the first 24 hour after gynecological surgery.
PMID- 27501599
TI - The Efficacy of Two Oxygen Therapy Devices (Nasal Cannula vs. Simple Mask) for
Preventing Hypoxemia after General Anesthesia: A Randomized Controlled Non
Inferiority Trial of 500 Patients.
AB - OBJECTIVE: To compare the efficacy of two oxygen devices (nasal cannula and mask)
and two flows for preventing hypoxemia in post anesthesia care unit (PACU).
MATERIAL AND METHOD: Five hundred (18-70 year old) patients were enrolled into a
randomized, controlled non-inferiority trial at Sirirai Hospital, Mahidol
University from May 2013 to December 2014. They received oxygen therapy after
general anesthesia according to their groups by computer-generated randomization.
Group I received oxygen nasal cannula 4 liters per minute and group II received
oxygen mask 5 liters per minute. Both methods gave comparable FiO2 (FiO2 = 0.35).
Inclusion criteria were elective surgery, American Society of Anesthesiologist
(ASA) physical status 1-3. Exclusion criteria were unstable pulmonary disease,
BMI > 35 kg/m2, baseline SpO2 < 94%, myopathy, alteration of consciousness, and
nasal problems. The high-risk operations for post operative hypoxemia were
excluded The efficacy of two oxygen devices and flows were compared in term of
preventing hypoxemia in PACU. RESULTS: Five hundred patients were analyzed (249
patients in the cannula group and 251 patients in the mask group). They were
comparable in demographics and operations. At PACU, none of 500 patients had SpO2
< 94% (non-inferiority trial, 95% CI-0.0152, 0.0152). They were mildly sedated or
fully awake and had no respiratory complications. CONCLUSION: In low risk
patients undergoing low risk operations, both nasal cannula or simple mask with
FiO2 = 0.35 are equally effective for preventing hypoxemia in PACU.
PMID- 27501600
TI - Appropriateness of Broad Spectrum Antibiotics for Severe Sepsis and Septic Shock
in the Emergency Department.
AB - OBJECTIVE: Determine the appropriateness of broad-spectrum antibiotics applied in
severe sepsis and septic shock in an emergency room and its impact on the
survival rate. MATERIAL AND METHOD: This was a prospective observational study in
an emergency room setting at a tertiary care facility where early goal-directed
therapy (EGDT) was applied for resuscitation of severe septic and septic shock
patients. The data recorded were the initial vital signs, SAP II score, time of
EGDT goals achieved (ScvO2> 70), time of antibiotics initiated, type of
antibiotics used, organisms that were identified, source of infection, initial
and final diagnosis, and outcome of treatment. The student's t-test and Mann
Whitney U test were used to compare survival rates between appropriate and
inappropriate antibiotics used. RESULTS: Seventy-eight newly diagnosed severe
septic and septic shock cases were treated per the EGDT protocol. There were 41
(52.6%) male and 37 (47.4) female patients. The organisms were identified by
hemoculture in 28 cases, 18 (64.3%) cases were gram-negative, seven (25.0%) cases
were gram-positive, and three (10.7%) were mixed organisms. The five most common
sites of infection were 30 (38.5%) cases of lung infection, 18 (23.1%) cases of
bacteremia, 16 (20.5%) of gastrointestinal tract infection, 15 (19.2%) cases were
genito-urinary tract infection, and six (7.7%) were skin and soft tissue
infection. The mean SAP II score was 44.2 +/- 15.4 and the mean time to initiate
antibiotics was 59 +/- 50 minute. Fifty-five cases (70.5%) were classified as
appropriate antibiotics group, 31 (56.4%) of the 55 cases survived, while only
nine (39.1%) of the 23 cases in the inappropriate group survived. This was not
statistically significant. CONCLUSION: The most common sources of infection of
septic patients were lung infection, bacteremia, gastrointestinal tract
infection, genito-urinary tract infection, and skin and soft tissue infection.
The hemocultures were positive in 58.9% of the cases and the common organisms
were E. coli, K. pneumonia, S. aureus, and S. pneumoniae. The immunocompromised,
multiple co-morbid and prolonged intubated patients should receive antibiotics to
cover ESBL-producing E. coli, P. aeruginosa, and A. baumannii.
PMID- 27501601
TI - The Performance of the Neck Circumference for a Difficult Laryngoscopy in Obese
Patients.
AB - BACKGROUND AND OBJECTIVE: There is conflicting evidence as to whether neck
circumference (NC) is related to a difficult laryngoscopy in obese patients. The
objectives of this study were to determine the performance of the NC in defining
a difficult laryngoscopy, and to identify factors predicting a difficult
laryngoscopy among those obese patients. MATERIAL AND METHOD: This prospective
study was conducted in adult patients with a body mass index (BM) of greater or
equal to 30 kg/m2 who underwent conventional endotracheal intubation.
Preoperative NC, the modified Mallampati test (MMT), the thyromental distance
(TM) and the sternomental distance (SM) were measured. A difficult laryngoscopy
was defined as a Cormack-Lehane laryngoscopic view of grade III or IV. RESULTS:
Five hundred patients (366 females; 134 males), with a mean BMI of 34.3 +/- 4.6
kg/m2 (minimum = 30.0 kg/m2, and maximum = 68.4 kg/m2) and who had elective
surgery planned, were enrolled. The incidence of a difficult laryngoscopy was
7.2%. The overall performance of the NC using the area under the receiver
operating characteristic curves of a difficult laryngoscopy was 0.574, with a 95%
confidence interval (CI) of 0.53 to 0.618. The optimal cutoff point of the NC for
a difficult laryngoscopy was 37.1 centimeters. It provided sensitivity and
specificity of 75.5% (95% CI 57.8, 87.9) and 42.5% (95% CI 37.9, 47.2). The
positive and negative predictive values were 9.2% and 95.6%. After multivariate
analysis, factors affecting a difficult laryngoscopy were high grades of MMT
(odds ratio (OR) 2.23, 95% CI 1.10, 4.50) and NC/TM (OR 1.78, 95% CI 1.15, 2.74).
CONCLUSION: The NC per se was not a good predictor of a difficult laryngoscopy.
However the ratio of the NC to the TM and the MMT were factors predicting a
difficult laryngoscopy in obese patients.
PMID- 27501602
TI - Prevalence and Characteristics of Abnormal Pre-Operative Chest X-Rays in Patients
Undergoing Elective Surgery.
AB - OBJECTIVE: To determine the prevalence of pre-operative abnormal chest x-rays (CX
Rs) in patients undergoing elective surgery, and to describe the management of
the patients with abnormal CXRs. In addition, we question whether the healthy
patients aged more than 45 years really needs pre-operative chest radiographs.
MATERIAL AND METHOD: Patients undergoing elective surgery between June 2013 and
May 2014 were recruited, and medical records were retrospectively reviewed.
RESULTS: Data for 960 patients was included CX Rs were abnormal in 485 patients
(50.5%), with cardiomegaly being the most common abnormality. Among patients who
had pre-operative abnormal CXRs, 91 patients (18.8%) required consultation or
other investigation pre-operatively, and three patients (0.6%) had their
treatment plans altered. Comparing between age groups, there was no different of
abnormal results (p-value = 0.606). CONCLUSION: Prevalence of pre-operative
abnormal CXRs was high; however, the abnormalities seldom led to changes in case
management.
PMID- 27501603
TI - Development of New Lemon-Lime Flavored Beverage for OGTT: Acceptability and
Reproducibility.
AB - BACKGROUND: The oral glucose tolerance test (OGTT) is essential procedure in both
screening and diagnosis of impaired glucose tolerance (IGT), impaired fasting
glucose (IFG) and diabetes mellitus (DM), but it is not easy to perform because
of intense sweetness of the 75-g glucose test beverage causing abdominal
discomfort post-testing. Therefore, the new formula of non-carbonated lemon-lime
flavored beverage was developed to increase its palatability and better
compliance. OBJECTIVE: To develop a new non-carbonated lemon-lime flavored
beverage to replace the standard beverage for OGTT Subsequently, the diagnostic
value and acceptability between the new formula and the traditional 75-g OGTT
formula were compared in healthy subjects. MATERIAL AND METHOD: The new lemon
lime flavored formula was developed to replace the standard beverage for OGTT by
adding 1,000 milligram of citric acid and 0.03 gram of lime flavor to 75 gram of
anhydrous glucose to a final volume of 300 ml. The study was conducted in 30
healthy subjects who underwent the traditional 75-gram OGTT test and the new
formula of OGTT beverage one week later, or vice versa, to access acceptability,
indices markers of insulin secretion, and insulin sensitivity. Palatability was
determined by rating on a 9-point Hedonic Scale. RESULTS: Thirty healthy subjects
(15 females) with the age of 33.2 +/- 7.5 years and body mass index of 22.9 +/-
3.5 kg/m2 were enrolled. No significant difference was found between plasma
glucose in 0, 30, 60, 90, and 120 minutes, insulin level (0 and 120 minutes) and
four insulin surrogate markers in both traditional 75-gram OGTT and new formula
of lemon-lime flavored OGTT beverage. The overall satisfaction score of the new
formula OGTT was better when compared with the scores of the traditional OGTT
(7.1 +/- 1.8 vs. 4.7 +/- 2.0). Only one subject complained about abdominal
discomfort in both episode of OGTT CONCLUSION: The modified lemon-lime flavored
beverage for OGTT demonstrated better acceptance in the subjects without
difference in plasma glucose values and OGTT derived parameters responses to OGTT
in comparison to the traditional formula.
PMID- 27501604
TI - Comparing the Success Rate of Radial Artery Cannulation under Ultrasound Guidance
and Palpation Technique in Adults.
AB - BACKGROUND: Previous studies have shown ultrasound guidance (USG)for arterial
cannulation being advantageous compared to palpation technique, but little is
known about its performance by novices. OBJECTIVE: This study was to compare the
utility of USG radial artery cannulation with palpation technique in terms of
success rate, real-time to placement, number of attempts and complications.
MATERIAL AND METHOD: After IRB approval, a randomized prospective study was
performed November 2009-October 2010. Ten third-year residents, having performed
USG vascular catheterization as yet less than 3 times, were coached on the pork
phantom during a workshop for real time ultrasound-guided vascular access. For
the study patients were randomized to US-guided technique (US-group) and
palpation (P-group); ten patients for each resident. RESULTS: One hundred adult
patients undergoing neurosurgery were enrolled. There were no statistically
significant differences between US-group vs. P-group in success rate (78% vs.
82%; p = 0.62), time to success (60 (12.8, 547.0) vs. 52 (6.9, 639.0) sec; p =
0.22), and number of attempts (1 (1, 4) vs. 1 (1, 3); p = 0.79). Most common
complication was puncture hematoma (US-group 26% vs. P-group 24%; p = 0.82).
Success was defined as no change in catheterization site, performer and
technique. CONCLUSION: Regarding success rate, attended time, or number of
attempts for radial arterial cannulation, we did not find any benefit of
ultrasound guidance compared to palpation technique. Our findings were not in
accordance to other trials. However, we have to consider operators in our study
being in experienced in ultrasound-guided procedures but not in palpation
techniques.
PMID- 27501605
TI - Severe Venous Air Embolism Related to Positioning in Posterior Cranial Fossa
Surgery in Siriraj Hospital.
AB - BACKGROUND: Posterior cranial fossa surgery is commonly performed under sitting
and horizontal position in our institution. Venous air embolism is a potentially
serious complication of neurosurgery especially in the sitting position.
OBJECTIVE: We aim to compare the incidence of severe venous air embolism and
other complications of both positions. MATERIAL AND METHOD: A retrospective
analysis of medical record was performed in 192 patients undergoing posterior
cranial fossa craniotomy from January 2010 to December 2013. Data collected from
the records included demographic profile, patient position, hemodynamic changes,
venous air embolism (VAE), blood loss/transfusion, duration of surgery,
postoperative complications, duration of ICU stay, and postoperative discharge
status. The definition of severe air embolism was identified as suspected VAE
with decreased systolic blood pressure greater than 20%. RESULTS: There were 92
patients in sitting position (SP) group and 100 patients in horizontal position
(HP) group. The incidence of severe venous air embolism was signficantly higher
in SP group compared with HP group (41.3% vs. 11.0%, p<0. 001). SP group had more
complications than HP group in both central nervous system (71% vs. 34.0%, p =
0.001), and cardiovascular system (17% vs. 6%, p = 0.001). Although postoperative
ventilator time in SP group was less than HP group (1.24 vs. 1.60 days, p =
0.029), ICU and hospital stay were not different in either group. CONCLUSION: The
incidence of severe venous air embolism detected by end tidal CO2 was
significantly higher in SP group. However, 11% of HP group were suspected of
severe air embolism.
PMID- 27501606
TI - Incidence of Abnormal Preoperative Blood Testing and Postoperative Complication
in Appendectomy Patients in Siriraj Hospital.
AB - BACKGROUND: A cute appendicitis is a common emergency surgical problem. Pre
operative complete blood count and urinalysis are used for supporting diagnosis.
Blood chemistry is also requested for patient's status evaluation despite limited
evidence of its cost-effectiveness. OBJECTIVE: The primary objective was to
determine the incidence of abnormal pre-operative blood chemistry result. The
secondary objectives were the relationship between preoperative abnormal blood
chemistry and postoperative complication and to find the risk factors of abnormal
blood chemistry. MATERIAL AND METHOD: 450 patients underwent emergency
appendectomy at Siriraj Hospital from January 1st, 2012 to March 31st, 2014 were
included in this retrospective descriptive study. Demographic data, blood
chemistry test result and postoperative complication were recorded. The incidence
of abnormal blood chemistry results was reported. Relationship between abnormal
laboratory results, postoperative complications and predisposing factors were
analyzed. RESULTS: The incidence of abnormal pre-operative serum BUN, creatinine,
sodium, potassium, bicarbonate and chloride were 19.1%, 35.4%, 26%, 24%, 32.9%
and 24.3%, respectively. Abnormal blood chemistry results were not associated
with postoperative complications. However ASA physical status equal or more than
3 and duration of symptoms > 48 hours are significantly associated with
postoperative complications (adjusted OR 2.91, 95% CI 1.04-8.13, p-value = 0.041
and adjusted OR 2.78, 95% CI 1.24-6.25, p-value = 0.013, respectively). The
predisposing factors of abnormal blood chemistry are ASA physical status equal or
more than 3 (adjusted odd ratio 4.27, 95% CI 1.25-14.65, p-value = 0.021) and
duration of symptoms > 48 hours (adjusted odd ratio 1.79, 95% CI 1.01-3.20, p
value = 0.047). CONCLUSION: There was no association between abnormal blood
chemistry result and postoperative complication. Preoperative blood chemistry
should be tested only if indicated.
PMID- 27501607
TI - Anesthetic Management for Esophageal Stent Placement in an Endoscopy Unit Outside
Operating Room.
AB - BACKGROUND: Esophageal stent placement is a minimally invasive procedure for
treatment of esophageal strictures that cannot be treated with surgical
procedure. It requires some forms of anesthesia. This procedure could be
performed in the operating room and in the endoscopy unit. OBJECTIVE: The study
is aimed to report and evaluate the choices and techniques, drugs used and
complications of anesthesia in the patients undergoing esophageal stent placement
procedure in an endoscopy unit outside the operating room in a developing
country. MATERIAL AND METHOD: Retrospectively analyzed the patients on whom
esophageal stent placement had been performed during the period of January, 2010
to December, 2012 in Siriraj Hospital in Thailand. The patients' characteristics,
pre-anesthetic problems, anesthetic techniques, drugs, duration of anesthesia,
and anesthesia-related complications were assessed and summarized by using
descriptive statistics. RESULTS: During the study period, there were 48
procedures. Mean age 63.7 +/- 13.4 years. The majority of them was male (72.9%)
and classified in ASA physical status II (52.1%). Mean duration of anesthesia was
60.6 +/- 36.1 minutes. Most common pre-anesthetic problems were hematologic
disease (64.6%), electrolyte imbalance (50.0%), respiratory disease (31.3%) and
hypertension (29.2%). General anesthesia with endotracheal tube (64.6%) was the
main anesthetic technique. The mainly used sedoanalgesic agents were propofol,
fentanyl and midazolam. The most common neuromuscular blocking drugs were
succinylcholine and atracurium. Additionally, sevoflurane was the most inhalation
agent. The overall anesthesia-related complication rate was 35.4%. Hypotension
(31.3%) was the most frequent anesthetic complication. CONCLUSION: All of the
esophageal stent placement procedures, general anesthesia and intravenous
sedation techniques could be performed effectively in the appropriate patients.
However, clinical signs should be carefully observed and the anesthetic personnel
had to optimize the patient's condition for safety and beware of complications.
PMID- 27501608
TI - Effectiveness of Postoperative Epidural Analgesia for Thoracic and Abdominal
Surgery in Siriraj Hospital.
AB - BACKGROUND: Epidural analgesia is the recommended analgesic technique in patients
having surgery with moderate to severe postoperative pain. Inadequate pain
control in patients receiving epidural analgesia frequently occurred in clinical
practice but the number of the success rate or the failure rate have not been
reported in our university hospital. OBJECTIVE: The aim of the prospective
descriptive study is to examine various data related to and evaluate the
effectiveness of the postoperative epidural analgesia in Siriraj Hospital, a
university hospital in Thailand. MATERIAL AND METHOD: Patients scheduled to have
elective thoracic or abdominal surgery under general anesthesia combined with
epidural analgesia from December 2014 to October 2015 were enrolled in this
study. Three hundred and sixty-four patients were finally analyzed. All data
about demographics, surgery, epidural techniques, postoperative pain scores at
rest and on movement, and postoperative complications were collected RESULTS: The
number of patients having acceptable postoperative pain score at rest at all time
period was 51.4%, (95% CI 46.3-56.5). Fifty patients (13.7%) in this group needed
intravenous rescue medication for breakthrough pain. The incidence of severe
postoperative pain at rest during running of epidural medication was 24.5% (95%
CI 20.3-29.1). One hundred patients (27.5%) experienced postoperative nausea and
vomiting; and 28 patients (7.7%) had episodes of hypotension. The incidences of
accidental dural puncture and post-dural puncture headache were 1.36% and 0.8%,
respectively. CONCLUSION: Inadequate postoperative analgesia with epidural
technique occurred in up to 50% of patients in this study in which the rescue
pain medication was necessary. In-depth analysis to identify associated factors
to improve the effectiveness of postoperative epidural analgesia should be
further investigated.
PMID- 27501609
TI - Pain after Major Craniotomy in a University Hospital: A Prospective Cohort Study.
AB - BACKGROUND: Pain after major craniotomy has been believed to be less severe than
the other operations. OBJECTIVE: To determine the incidence and risk factors of
moderate to severe pain after major craniotomy. MATERIAL AND METHOD: This is a
prospective observational study in a neurosurgical intensive care unit and wards
of a university, tertiary hospital. After institutional IRB approval, patients
undergoing major craniotomy during May 2011-August 2012 were interviewed
preoperatively and 24 and 48 hours postoperatively. Demographic data,
preoperative anxiety scores, operative data and postoperative pain
characteristics were recorded. RESULTS: Two hundred and eighty patients completed
the study. The incidence of moderate to severe pain was 75%. Mean pain score
during 24 and 48 hours were 5.5 +/- 2.7 and 3.5 +/- 2.6, respectively. Univariate
analysis identified age under 45 years and perioperative steroid therapy as
predictors of moderate to severe postoperative pain. Using multivariate analysis,
only age under 45 years was a significant risk factor. Patients' satisfaction
scores were good in both mild and moderate to severe pain groups (9.49 +/- 1.08
and 8.37 +/- 1.76). During postoperative period, almost all of the patients
received intravenous opioid and oral acetaminophen for pain treatment. No
respiratory depression occurred, but postoperative nausea and vomiting occurred
in 51.7% and pruritus in 23.6%. CONCLUSION: Incidence of pain after craniotomy
was high especially in younger age group, which is not in accordance with all
similar reports. However we believe pain management after major craniotomy in our
hospital requires improvement.
PMID- 27501610
TI - Postoperative Pain Management and the Risk Factors in Major Operation: A Baseline
Study of Acute Pain Service, Siriraj Hospital.
AB - BACKGROUND: Acute pain service (APS) has been set up at Siriraj Hospital with the
aim of providing postoperative pain management for patients receiving anesthetic
pain control and other complicated cases undergoing major operations. OBJECTIVE:
To identify the incidence of moderate to severe postoperative pain and its risk
factors. To describe the techniques used and adverse effects in patients under
APS care. MATERIAL AND METHOD: A prospective study in 340 surgical patients under
APS care from January to September 2008 was performed. Data were obtained from
medical records and patients' answers during 48 hours postoperatively. RESULTS:
The incidences of postoperative pain scores 4-10 at 24 and 48 hours were 28.8%
and 7.4%, with median pain intensity (0-10, [interquartile range]) of 2.5 [1.0
4.0] and 1.0 [0.0-2.0], respectively. The risk factors related to pain score 4-10
included analgesic intake for > 2 consecutive weeks prior to operation, type of
surgery with severe degree of pain and age 65 years (odds ratios [95% CI] of 7.12
[1.92, 26.44], 6.17 [1.37, 27.77], and 1.87 [1.07, 3.29], respectively). Of the
patients, 67.9% received epidural block for postoperative analgesia. The
incidences of nausea/vomiting and itching that needed treatment were 12.4% and
9.4%, respectively. CONCLUSION: Risk factors that should be concerned were age <=
65 years, pre-operative prolonged analgesic use and surgeries with expected
severe degree of pain.
PMID- 27501611
TI - Psychometric Validity and Reliability of the Thai Version of the Neuropathic Pain
Symptom Inventory.
AB - OBJECTIVE: The aim of this study was to evaluate validity and reliability of the
Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T) in Thai patients
with neuropathic pain. Although the Thai version of Neuropathic Pain Symptom
Inventory (NPSI-T) has been linguistically validated, the tool has to be
psychometrically validated before applying to neuropathic pain patients in daily
practice. MATERIAL AND METHOD: Forty Thai patients with diagnosis of neuropathic
pain were enrolled to the study and were evaluated by visual analog scale (VAS),
the Thai version of Neuropathic Pain Diagnostic Questionnaire (DN4-T) and NPSI-T
questionnaires. Four hours later the patients were asked to perform retest NPSI-T
and to evaluate the understanding of each NPSI-T question. RESULTS: The total
score of NPSI-T questionnaire was statistically correlated to visual analog scale
(VAS) (Spearman's correlation coefficient = 0.599, p < 0.001) and neuropathic
pain diagnostic questionnaire (DN4-T) (Spearman's correlation coefficient =
0.695, p < 0.001). The reliability was determined by Intraclass correlation
coefficient (ICC), an excellent interobserver agreement (ICC > 0.8) and good
agreement (ICC 0.6-0.8) were presented in 30% and 70% of the questionnaire,
respectively. CONCLUSION: The study demonstrated validity and reliability of the
NPSI-T for assessing the neuropathic pain in Thai patients.
PMID- 27501612
TI - Effective Pain Management for Inpatients at Siriraj Hospital: A Retrospective
Study.
AB - BACKGROUND AND OBJECTIVE: The prevalence of severe cancer and non-cancer pain
among in patients has been reported at rates ranging from 15% to 36%. We examined
the effectiveness of the pain management provided to inpatients by the Siriraj
Pain Clinic. MATERIAL AND METHOD: A retrospective chart review was conducted
among inpatients who had consulted the clinic between January 2013 and December
2014. Patients with a numeric pain rating scale (NRS) 4 on the day of
consultation, those discharged within seven days, and postoperative patients were
excluded. Successful pain control was defined as NRS <= 4 within seven days of
the initial consultation. RESULTS: We identified 352 eligible patients, of which
231 (65.4%) had cancer pain. Only 42.6% achieved successful pain control. An
absence of psychological problems (odds ratio (OR) 2.1, 95% confidence interval
(CI) 1.1-4.2; p = 0.010); an initial NRS < 7 (OR 1.9, 95% CI 1.2-3.0; p = 0.008);
the use of either a non-steroidal anti-inflammatory drugs (NSAIDs) or a Coxibs
(OR 2.3, 95% CI 1.3-3.9; p = 0.017), and abdominal pain (OR 2.7, 95% CI 1.5-4.7;
p =0.008) were factors associated with successful pain control. CONCLUSION:
Adequate pain control was achieved in less than half of the inpatients in our
institution. Psychological disturbance and severe pain predicted unsatisfactory
pain control.
PMID- 27501613
TI - Assessment of Pain Severity after Radiofrequency Ablation in Patients with
Hepatocellular Carcinoma.
AB - OBJECTIVE: To find the incidence of moderate to severe pain after percutaneous
radiofrequency ablation (RFA) in patients with hepatocellular carcinoma and to
identify the factors affecting unwanted pain scores. MATERIAL AND METHOD: This
prospective study was conducted on patients who underwent percutaneous
radiofrequency ablation under intravenous sedation and local anesthesia. The pain
scores were obtained from 18 to 24 hours after the procedure. Moderate to severe
pain was defined as a value of 4 or more on the Numeric Rating Scale (NRS). Data
on patients' factors, tumor characteristics, procedural factors, anesthetic
management, postoperative treatment and perioperative complication was collected
RESULTS: A total of 190 patients were enrolled, comprised of 134 men (70.5%) and
56 women (29.5%). The mean age of the patients was 63.3 +/- 11.1 years. The
incidence of moderate to severe pain on movement (an NRS value equal to or
greater than 4) was 11.6% (22 out of 190 patients). A univariate analysis
revealed that two factors--patients with multiple tumors (more than two tumors),
and an ablation time of greater than 30 minutes--seemed to be related to an NRS
equal to or greater than 4. Nevertheless, after entering those two factors into a
multiple regression model, neither factor was associated with the moderate to
severe pain scores. CONCLUSION: The incidence of undesired pain scores after
percutaneous radiofrequency ablation in our institution was around 10%, and the
rate of complication was very low.
PMID- 27501614
TI - Femoral Nerve Block versus Intra-Articular Infiltration: A Preliminary Study of
Analgesic Effects and Quadriceps Strength in Patients Undergoing Arthroscopic
Anterior Cruciate Ligament Reconstruction.
AB - BACKGROUND: Adequate analgesia and early rehabilitation is necessary for
arthroscopic anterior cruciate ligament reconstruction (A CLR) surgery.
OBJECTIVE: To compare analgesia and quadriceps strength after femoral nerve block
(FNB) with intra-articular infiltration (IA) using 0.25% bupivacaine for ACLR
with patella tendon graft. MATERIAL AND METHOD: Forty patients were randomized to
receive FNB under ultrasound guidance with 20 mL of bupivacaine or IA with 15 mL
of bupivacaine into the knee joint and 5 mL infiltrated along the incision sites
including portal sites at the end of surgery. All patients received intravenous
ketorolac at wound closure. Data regarding demographic, time to first pain, time
to first morphine requirement, morphine usage, pain scores and quadriceps
strength were recorded. RESULTS: Significant difference in quadriceps strength
was shown. Ninety percent of patients in Group IA and fifty-five percent of
patients in Group FNB had good ability to extend knee at 24 hours after surgery
(p = 0.013). No differences were found in demographic data, time to first pain,
time to first morphine requirement, post operative pain scores and morphine
consumption, CONCLUSION: The preliminary results demonstrated that IA has an
effect on quadriceps strength less than FNB while provide comparable
postoperative analgesia after patellar tendon graft ACLR.
PMID- 27501615
TI - Incidence of Delayed Recovery from Femoral Nerve Block in Total Knee
Arthroplasty.
AB - OBJECTIVE: Femoral nerve block has been proven as an effective analgesia for
total knee arthroplasty (TKA). Delayed recovery from nerve block can result in
serious complication during postoperative period. This prospective, single
center, observational study investigated the incidence in delayed recovery from
femoral nerve block more than 24 hours postoperatively. MATERIAL AND METHOD: Two
hundred and forty patients with femoral nerve block as part of anesthesia plan
for elective unilateral TKA were recruited into study. Participants were assessed
for sensory or motor impairment lasting longer than 24 hours post operation.
Factors associated with delayed recovery from femoral nerve block were analyzed.
RESULTS: Five patients (incidence = 2.08%) reported sensory or motor impairment
more than 24 hours post operation. All of the patients could ambulate within 4
days post operation without permanent nerve injury or serious complication.
Higher dose of local anesthetic agent using for femoral nerve block showed
association with the delayed recovery (p-value = 0.01). CONCLUSION: This study
demonstrated 2.08% incidence in delayed recovery from femoral nerve block. High
concentration and dose of local anesthetic agent may lead to fall during early
ambulatory period.
PMID- 27501616
TI - Onset Time of 2% Lidocaine and 0.5% Bupivacaine Mixture versus 0.5% Bupivacaine
Alone using Ultrasound and Double Nerve Stimulation for Infraclavicular Brachial
Plexus Anesthesia in ESRD Patients Undergoing Arteriovenous Fistula Creation.
AB - OBJECTIVE: To reduce the onset of 0.5% bupivacaine by adding 2% lidocaine with
0.5% bupivacaine for ultrasound-guided and double stimulation technique at
musculocutaneous and radial nerve for infraclavicular brachial plexus block.
DESIGN: Prospective randomized double-blinded, controlled trial study. MATERIAL
AND METHOD: 90 patients undergoing creation of arteriovenous fistula under
ultrasound-guided infraclavicular brachial plexus block were randomized into 2
groups. Gr B (46 patients) received 0.5% bupivacaine 30 mL and Gr BL (44
patients) received mixture of 0.5% bupivacaine 20 mL and 2% lidocaine 10 mL. The
onset of sensory block were assessed by response to pinprick (grading: 0 = no
sensation, 1 = hypoesthesia, and 2 = normal sensation). Rescue analgesia during
the operation, duration of sensory and motor blockade were recorded. Surgeon and
patient satisfactions are also evaluated using 6-point scale (0 = dissatisfied to
5 = very satisfied). RESULTS: There were no significant difference in the onset
time of either group. Duration of sensory and motor block was not different.
Surgeons' and patients' satisfaction were also not significantly different
between the groups. CONCLUSION: Mixing 2% lidocaine with 0.5% bupivacaine to the
final concentration of 0.67%for lidocaine and 0.33% for bupivacaine does not
reduce the onset of ultrasound-guided infraclavicular brachial plexus block.
PMID- 27501617
TI - The Success of MRI without Sedations in 6-15 Years Old Pediatric Patients after
Watching MRI Introductory Video.
AB - High-quality imaging is important for effective diagnosis and treatment in
pediatrics. In order to obtain such high-quality image, the patient has to be
still during the scan, which may or may not require sedation depending on each
patient's condition. This study, conducted at Siriraj Hospital in Bangkok,
Thailand, focused on patient factors that influence success of radiologic
procedures for patients without sedation. The participants were children aged
between 6 to 15 years old. Participants and parents were asked to watch a 5
minute MRI introductory video, which was specially designed for children.
Participants would then make decision whether they needed sedation or not. Fifty
five patients were included in this study. There were 37 patients agreed with non
sedation technique. Ninety-four percent of children (35/37) who decided to
proceed without sedation, were able to complete their MRI sessions. Factors
identified from this study that determined success in MRI without sedation in 6
15 years old patients were children at aged 11-15 years and children who had
previous exposure to MRI without need of sedation/anesthesia. There was no
anesthetic complication in sedation group.
PMID- 27501618
TI - Anesthetic Techniques and Incidence of Complications in Fetoscopic Surgery.
AB - BACKGROUND: Nowadays, fetoscopic surgery has been accepted to be a procedure to
correct numerous congenital anomalies. This operation can be successfully done
under general, regional or local anesthesia with sedation. Incidence of
complications from anesthesia in fetoscopic surgery has not been reported in
Thailand. OBJECTIVE: To describe anesthetic techniques and incidence of
complications in fetoscopic surgery. MATERIAL AND METHOD: Data of 152 pregnant
women undergoing fetoscopic surgery in a single university hospital was
retrospectively chart reviewed from June 2005 to November 2015. Patient
characteristics, choices of anesthesia, medication used, intraoperative data and
complications were collected. RESULTS: During the study period, spinal anesthesia
was the most popular technique used in fetoscopic surgery (71%). Other anesthetic
techniques used were general anesthesia with endotracheal tube (GA) (20.5%),
epidural anesthesia (1.3%), combined spinal and epidural anesthesia (0.7%),
failed spinal anesthesia converting to GA (2.6%) and local anesthesia with
sedation (3.9%). Most frequent anesthetic-related complication was maternal
hypotension which occurs in 115 out of 152 patients (75.6%). All of 5 cases
(3.3%) of postoperative pulmonary edema received SA. Fetal death after operation
was 25 in 152 records (16.4%). None of patients received GA experienced
desaturation, pulmonary aspiration, failed intubation or pulmonary edema.
CONCLUSION: Spinal anesthesia (SA) is the most frequent technique used for
fetoscopy, and hypotension is the most common complication. Since pulmonary edema
was also found, judicious perioperative fluid management should be implemented to
prevent postoperative pulmonary edema.
PMID- 27501619
TI - Reference Values for Umbilical Cord Blood Gases of Newborns Delivered by Elective
Cesarean Section.
AB - BACKGROUND: Umbilical cord blood gas values are better indicators of perinatal
asphyxia than Apgar scores. Many studies have reported normal ranges of umbilical
cord blood gases, which vary greatly due to many factors. This study aimed to
establish the reference values of umbilical cord blood gases of normal cesarean
newborns in a university hospital setting. MATERIAL AND METHOD: Blood samples
from the umbilical artery and vein were collected from 160 newborns delivered by
elective cesarean section. The indications for caesarean section were not due to
fetal distress, intrauterine growth retardation, or non-reassuring fetal heart
rate. The blood samples were collected immediately after birth in the operating
room and then sent for blood-gas analysis. The blood-gas values were
statistically analyzed and reported. RESULTS: The cord blood collected from 160
newborns was analyzed in this study. Seventy-eight percent (115) of the
parturients were hypotensive before delivery. All Apgar scores at one and five
minutes after delivery were at least 7. The calculated reference range of the
umbilical arterial pH was 7.18-7.42, of pO2was 6.43-29.43 mmHg, of pCO2was 33.44
66.56 mmHg, and of HCO3was 15.60-30.70 mEq/L. The reference range obtained for
the umbilical venous pH was 7.28-7.44,for pO2was 13.97-37.13 mmHg, for pCO2was
30.70-57.0 mmHg, and for HCO3was 18.50-29.90 mEq/L. CONCLUSION: The study
determined normal reference values as a result of umbilical cord blood gas
analyses.
PMID- 27501620
TI - 50th Year Anniversary of Department of Anesthesiology, Faculty of Medicine
Siriraj Hospital, Mahidol University.
AB - Department of Anesthesiology, Faculty of Medicine Siriraj Hospital, has started
to be a formal anesthesia division, divided from division of Surgery in 1965;
hence our 50th year anniversary in 2015. Research is now a priority and mandatory
mission, according to the vision of Mahidol University. Second mission is to
teach and train, and we produce the highest number of states-of-the-art
anesthesiologists and anesthetic nurses each year Curriculum and training are
being continuously improved. From a small unit, now it is one of the largest
departments and extends the service, our third mission, to more than only in the
operating theaters. We look after pre-anesthesia assessment, inside and outside
operating room anesthesia, post-operative pain relief Intensive Care Unit, and
chronic pain management. The number of patients and their diseases increase; so
do the complexities of surgeries. There are tremendous changes in drugs and
equipment. There is the fourth mission on administration, IT and resource
management. And the fifth mission which is corporate social responsibility.
However, we still believe that compassion, responsibility and integrity are most
important. We have taught and tried to live by the teaching of HRH the King's
Father. And these will contribute to our progress and shine in the next 50 years.
PMID- 27501621
TI - Quality of Anesthesia Care in a University Hospital in Thailand.
AB - BACKGROUND: Service quality is an important factor, which value differs between
the patient's satisfaction and expectation. The patient's expectations are
important factors for development. This service quality is a key part for
improvement of our anesthesia service. In general, an improvement in service
design and delivery helps to achieve higher levels of the service quality.
OBJECTIVE: To evaluate the level of patient's expectation, patient's satisfaction
and the quality of anesthesia care in a university hospital in Thailand MATERIAL
AND METHOD: The patient satisfaction questionnaire, developed from service
quality criteria and patient satisfaction questionnaire (PSQ-18), was applied to
evaluate 467 in patients 24-72 hours after anesthesia care. The
patients'expectation was also assessed A proportional stratified randomized
allocation was done. The questionnaire consisted of three dimensions; 1)
structure: reliability & empathy, 2) process: assurance & tangible and 3) result:
responsiveness. Data expectation and satisfaction were analyzed with mean,
standard deviation, t-test, ANOVA and normalized gain for the quality of
anesthesia care. RESULTS: The patient's satisfaction in our anesthesia care is
relatively high. The mean patient's satisfaction score is significantly higher
than the mean patient's expectation in all dimensions. This study indicated that
an anesthesia service in our hospital was a high quality service in the inpatient
aspects. CONCLUSION: Patient's expectation and satisfaction with anesthesia
services in our setting was relatively high. Although most patients never had
been any expectation regarding anesthesia service, the information and the
involvement in decision- making were the most requirements of the adult
inpatients.
PMID- 27501622
TI - Development of An Assessment Test for An Anesthetic Machine.
AB - OBJECTIVE: The study is aimed to develop and assess the quality of an evaluation
form used to evaluate the nurse anesthetic trainees' skills in undertaking a pre
use check of an anesthetic machine. MATERIAL AND METHOD: An evaluation form
comprising 25 items was developed, informed by the guidelines published by
national anesthesiologist societies and refined to reflect the anesthetic machine
used in our institution. The item-checking included the cylinder supplies and
medical gas pipelines, vaporizer back bar, ventilator anesthetic breathing
system, scavenging system and emergency back-up equipment. The authors sought the
opinions of five experienced anesthetic trainers to judge the validity of the
content. The authors measured its inter-rater reliability when used by two
achievement scores evaluating the performance of 36 nurse anesthetic trainees
undertaking 15-minute anesthetic machine checks and test-retest the reliability
correlation scores between the two performances in the seven days interval.
RESULTS: The five experienced anesthesiologists agreed that the evaluation form
accurately reflected the objectives of anesthetic machine checking, equating to
an index of congruency of 1.00. The inter-rater reliability of the independent
assessors scoring was 0.977 (p = 0.01) and the test-retest reliability was 0.883
(p = 0.01). CONCLUSION: An evaluation form proved to be a reliable and effective
tool for assessing the anesthetic nurse trainees' checking of an anesthetic
machine before the use. This evaluation form was brief clear and practical to
use, and should help to improve anesthetic nurse education and the patient
safety.
PMID- 27501623
TI - A Contemporary Clinical Assessment of Historical Findings of a 14,000 Year Old
Tooth.
AB - A recent publication in Nature--Scientific Reports identified a 14,000-year-old
tooth that apparently had undergone a dental procedure to remove dental caries.
This report is well detailed and focused on the discovery of what appeared to be
dental caries manipulation in the Late Upper Palaeolithic Era in a human specimen
(Villabruna) from a burial site in Northern Italy. Modern technology was used to
assess this finding and provide a reasonable explanation based on specific enamel
chipping observed in the uppermost mesial margin of the tooth cavity. While
details of the discovery were based primarily on the tooth cavity that was
identified and the specific characteristics it displayed, upon review of the
report other observations not reported or assessed may suggest additional
considerations for contemporary dentistry. The purpose of this article is to
attempt to provide a plausible clinical perspective on these additional
observation and assessments along with identifying questions as to the importance
of these conclusions.
PMID- 27501624
TI - The Brisbane Dental Hospital Building: "The Palace" An Era Ends.
AB - Constitutional, educational, humanitarian and political considerations
underpinned the design and construction of the Brisbane Dental Hospital Building,
often colloquially referred to as "The Palace." The Queensland Heritage Council's
listing of the Brisbane Dental Hospital Building on The Queensland Heritage
Register in 1999 confirms the cultural significance of Nowland's architectural
signature, the historical importance of the Wickham Park precinct and prior
students' connection with the building. Influences on decisions determining the
location, grand design and timing of construction of the Brisbane Dental Hospital
Building emanated from a far bigger and largely unrecorded political picture. The
authors argue that the political context in two tiers of government, the timing
and nature of the proposal, town planning issues, the exigencies of the caries
epidemic and Forgan Smith's post-Depression economic reconstruction across
Queensland underpinned the project. Hanlon's personal attributes and disdain for
the autonomy of the dental profession, together with his desire to reform dental
education and to establish statewide government-administred dental clinics, were
also relevant. Accordingly, the BDHD portrayed aspiration, purpose, symbolism,
and vision. This paper, essentially an integration of dental and mainstream
history, assembles and analyzes hitherto scattered and unpublished evidence to
fill a gap in the current literature.
PMID- 27501625
TI - Dental Trade Cards XLIII.
PMID- 27501627
TI - Creating and Maintaining a Culture of Safety--Our Role.
PMID- 27501626
TI - Promoting Resilience Among Patients with End Stage Renal Disease.
PMID- 27501628
TI - Contrasting Perceptions of Home Dialysis Therapies Among In-Center and Home
Dialysis Staff.
AB - Home dialysis offers many advantages over in-center dialysis, but peritoneal
dialysis and home hemodialysis are infrequently used. To better understand why, a
survey of dialysis healthcare professionals (N = 273) in the United States was
conducted to assess their knowledge, perceptions, and beliefs about home dialysis
modalities. Most survey respondents demonstrated a lack of knowledge about home
dialysis and perceived many barriers to home therapy, which may affect patient
modality choice; however, 90% of respondents stated they would choose home
dialysis for themselves if they required dialysis. Additional staff education may
help reduce misperceptions, address knowledge gaps, and subsequently, increase
use of home modalities.
PMID- 27501629
TI - Improving the Care of Patients with Chronic Kidney Disease Using Group Visits: A
Pilot Study to Reflect an Emphasis on the Patients Rather Than the Disease.
AB - This two-group, repeated-measures experimental study assessed the efficacy of a
nurse practitioner-facilitated chronic kidney disease (CKD) group visit (GV)
model versus usual nephrology care for patients with Stage 4 CKD. The study
enrolled patients from two sites of an outpatient nephrology practice (n = 30)
and randomized subjects to usual care (n = 14) or to the GV model (n = 16). Data
regarding CKD knowledge, self-efficacy/disease self-management, and physiologic
measures were collected at baseline, 6 months, and 9 months. Satisfaction was
obtained at 6 months and 9 months. Usual nephrology office visit components were
maintained during six monthly GVs, with group discussions of CKD-related topies.
Results indicated a statistical improvement in CKD knowledge for both groups
(F[1.498, 34.446] = 6.363, p = 0.008). An upward trend in mean scores for self
management subscales and self-efficacy scores was demonstrated in the GV
patients, with no improvement found in the usual care group. Twenty-six of 30
patients completed the study, with 92% attendance in the GV group. GV
satisfaction was high.
PMID- 27501630
TI - Non-Biological Barriers to Referral and the Pre-Kidney Transplant Evaluation
Among African Americans in the United States: A Systematic Review.
AB - African Americans face a disproportionate burden related to the incidence of end
stage renal disease. A literature search was conducted for research articles
published between 2006-2015 to synthesize current literature related to non
biological barriers to early stages of the pre-kidney transplant continuum for
African Americans in the United States. Twenty-four articles were included in the
final sample. Eleven barriers were identified. Barriers were categorized as
socioeconomic-based barriers, culture-based barriers, and knowledge-based
barriers. Resources to develop educational interventions for both patients and
providers may help reduce existing barriers.
PMID- 27501631
TI - Experiences of Patients on Outpatient Hemodialysis Therapy Who Are Anticipating a
Transplant.
AB - The person with kidney failure may experience many lifestyle disruptions that
initiate distressing responses. This article reports on the results of a
phenomenological study that explored the experiences of patients with kidney
failure who were receiving outpatient hemodialysis therapy and who were either on
the transplant list or in the process of being assessed to get on the transplant
list. The participants described the existential distress they endured as a
result of living with this disease and treatment; however, the participants'
descriptions of distress were different than the psychological perspective of
emotional distress depicted in the existing research. The information provided in
this article can enhance nurses' ability to recognize and respond more
appropriately to the distressing moods experienced by patients with kidney
failure on outpatient hemodialysis.
PMID- 27501632
TI - Home Dialysis Modalities: Educational Barriers to Utilization.
AB - In the United States, an increasing number of individuals are being diagnosed
with end stage renal disease requiring renal replacement therapy. Home dialysis
modalities are an available option in lieu of in-center hemodialysis therapy for
these individuals, but are vastly underutilized in the U.S. for multiple reasons.
Both healthcare providers and individuals requiring renal replacement therapy are
frequently unaware these modalities are an available alternative to in-center
hemodialysis and of the potential benefits related to home modality use. Lack of
healthcare provider and patient education regarding home modalities is a primary
factor related to underutilization.
PMID- 27501633
TI - The Nephrology Clinical Research Nurse Role: Potential Role Conflicts.
AB - Clinical research nursing is becoming more visible to nephrology professionals.
As more nephrology practices and units are participating in clinical trials,
clinical research nursing is gaining interest as a career niche among nephrology
nurses. This unique specialty requires that nephrology clinical nurse nurses
(CRNs) reconcile the roles of nurse as caregiver and nurse as researcher, which
may result in a role conflict. Nephrology nurses should be aware that they may
experience this role conflict when transitioning from patient care to a position
as a clinical research nurse. These nurses can rely on the American Nurses
Association's Code of Ethics for Nurses and the Oncology Nursing Society's
Oncology Clinical Trials Nurse Competencies to help reconcile the potential role
conflict.
PMID- 27501634
TI - Living with a Change in Dialysis Modalities: A Case Study.
AB - Nephrology nurses play a major role in every aspect of caring for patients on
dialysis. It is always challenging to witness patients and families struggling
through dialysis modality changes coupled with end-of-life decisions. Open
discussions and care provided by an interdisciplinary team approach provides the
foundational structure for quality care necessary for this population. In the
case of Mr. T., a dialysis modality change was a necessary change in his life.
The FNP PCP played a significant role in coordinating his care to achieve the
desired outcomes and ensure there was a coordinated team approach.
PMID- 27501635
TI - The Role of Nephrology Nurses in the Selection of the Peritoneal Dialysis
Catheter and Exit Site Location.
PMID- 27501636
TI - Social Work's Grand Challenges: Mobilizing the Profession.
PMID- 27501637
TI - Mechanisms of Familial Influence on Reentry among Formerly Incarcerated Latino
Men.
AB - In the United States more than 10,000 people are released from state and federal
prisons every week and often reenter the communities in which they were arrested.
Formerly incarcerated individuals face considerable challenges to securing
employment and housing. Subsequently, approximately two-thirds of former
prisoners are rearrested within three years of their release. Latino men
represent the fastest growing ethnic group of prisoners in the United States with
unique cultural and social needs during the reentry process. The present study
examined the role of the family in the reentry process through in-depth
interviews (N = 16) with formerly incarcerated Latino men (FILM). The authors
sought to identify familial processes specific to Latino men with potential to
affect engagement and participation in reentry programs. Findings suggest that
family mechanisms of social control and social support influence FILM's reentry.
Social work practitioners who work with this growing population can engage
familial processes to prevent recidivism and promote desistance.
PMID- 27501638
TI - Social Work-Business Sector Collaboration in Pursuit of Economic Justice.
AB - This article examines social workers' perceptions, experiences, and prospects
regarding working in the business sector after participating in an MSW field
practicum with a local microlending program. Social workers' insights suggest
that cross-sector collaboration leads to vast opportunities not only for the
populations served by the collaborative efforts, but also for social work as a
profession. However, several challenges are evealed, including social workers'
unfamiliarity with business operations, the business sector's narrow
understanding of social workers' roles, and divisions between participants in
interprofessional collaboration. This article calls for enhancing the role of
social work to maximize its impact on economic development through further
research and tangible cross-sector projects.
PMID- 27501639
TI - Promoting Young People's Participation: Exploring Social Work's Contribution to
the Literature.
AB - In the National Association of Social Workers' Code of Ethics, social workers are
called on to promote meaningful involvement in decision making among vulnerable
populations. The ethical imperatives and social justice implications associated
with unequal participation suggest that the field of social work is uniquely
situated to lead research and practice in the area of youth civic engagement.
This article examines the current state of the social work literature regarding
how young people participate civically. Authors identified 113 articles on this
topic published over the past decade in journals with a large presence in social
work or by social work authors. They present the findings of their exploratory
research, with a focus on describing where this research is being published, the
range of research foci, and the terms used to describe this work. Increased
attention to promoting youth civic engagement is needed in the profession's core
journals. Based on the analysis of this literature, they recommend moving toward
a cohesive body of social work scholarship that includes increased collaboration
among scholars, more unified terms and language, increased range of research foci
and methodologies, and more rigorous and comparative testing of strategies by
which youths participate civically.
PMID- 27501640
TI - The Affordable Care Act, Substance Use Disorders, and Low-Income Clients:
Implications for Social Work.
AB - Social workers are leaders in the substance abuse services field and may often
work in substance use disorder (SUD) education, prevention, assessment,
treatment, or resource coordination and case management roles. As the Patient
Protection and Affordable Care Act (ACA) (2010) drives changes in the fields of
health and behavioral health, social workers have an opportunity to lead
structural changes at the micro and macro levels that will have a positive impact
on low-income clients with SUDs. In this article, authors examine the current
state of SUDs and health care access, the impact of the ACA on the field, and
implications for social work practice and education. Social workers should seek
specialized education and credentialing in SUD services, know how to help clients
apply for health care coverage, and advocate for integrated substance abuse
treatment and health care programs and an expansion of Medicaid in their local
communities. Social workers are well positioned to be a voice for clients to
ensure that the current structural changes result in a better, integrated system
of care that is able to respond to the needs of low-income clients with SUDs.
PMID- 27501641
TI - Out-of-School Suspensions of Black Youths: Culture, Ability, Disability, Gender,
and Perspective.
AB - Racial disproportionality in out-of-school suspensions is a persistent social
justice issue in public schools. This article examines out-of-school suspensions
of four black youths from the perspectives of the youths, their caregivers, and
educators. The case involving David, a 14-year-old African American with a
learning disability, illustrates the challenges of students experiencing the
intersection of disability and race. The case involving George, a 14-year-old
Liberian immigrant, illustrates how parents and teachers may form alliances
around shared goals and values despite profound cultural differences in
understanding of youths' misbehavior. The case involving Nina, a 12-year-old
African American, illustrates how educators' failure to consider the context of
her misbehaviors as responses to sexual harassment, along with their subsequent
harsh punishment and failure to protect her, led to her disengagement from
school. The case involving Craig, a 16-year-old African American, provides a
glimpse into how the use of criminal justice language to refer to youths'
misbehaviors can support the development of a criminalized self- and social
identity. These cases illustrate the diversity of black students--including
ability, disability, culture, and gender--and how events surrounding suspensions
are interpreted by students, caregivers, and educators. Understanding such
diversity will undergird implementation of effective alternatives to suspensions.
PMID- 27501642
TI - Feminist Social Work: Practice and Theory of Practice.
AB - Although feminist social work has been practiced in Israel since the 1970s,
little has been written about it. This qualitative study aims to fill this gap by
documenting and conceptualizing feminist theory of practice and actual practice
based on interviews with 12 feminist social workers. Findings reveal that the
interviewees perceive feminist practice as significantly different from
traditional social work practice based on four analytical principles: (1) gender
analysis, (2) awareness of power relations, (3) analysis of welfare services as
structures of oppression, and (4) utilization of feminist language, as well as 10
principles of action. The principles are discussed in the context of feminist
social work in Israel and in light of feminist principles described in
international literature.
PMID- 27501644
TI - Taking a Timeout to Ensure Well-Being: Social Work Involvement in College Sports.
PMID- 27501643
TI - Toward Complete Inclusion: Lesbian, Gay, Bisexual, and Transgender Military
Service Members after Repeal of Don't Ask, Don't Tell.
AB - The 2010 repeal of Don't Ask, Don't Tell (DADT) is one example of how U.S. public
policy has shifted toward greater inclusion of lesbian, gay, and bisexual (LGB)
individuals. The repeal of DADT reversed the practice of discharging LGB service
members on the basis of sexual identity. LGB service members may now serve their
country without fear of direct repercussions stemming from sexual identity.
Though it is a statutory step toward parity, DADT repeal does not address a
number of cultural and institutional inequities that continue to hinder full
inclusion of sexual minority service members. Notably, as discussed in this
article, DADT largely ignores issues facing the transgender population. This
study examines remaining inequities and their ramifications for lesbian, gay,
bisexual, and transgender service members and their families. The article
concludes with practice and policy recommendations for culturally competent
social work practice with military service members across the sexual identity
spectrum.
PMID- 27501645
TI - The Social Worker, Psychotropic Medication, and Right to Refuse.
PMID- 27501646
TI - Agency in Vulnerable Families: A Critical Response to Goh.
PMID- 27501647
TI - On Combat Anesthesia.
PMID- 27501648
TI - Response.
PMID- 27501649
TI - Hazardous Intraoperative Behaviors: What's at Risk?.
PMID- 27501650
TI - Effects of a 30-mL Epidural Normal Saline Bolus on Time to Full Motor Recovery in
Parturients Who Received Patient-Controlled Epidural Analgesia With 0.125%
Bupivacaine With 2 ug/mL of Fentanyl.
AB - Previous research suggests that an epidural bolus of 30 mL of normal saline after
vaginal delivery may decrease the time for recovery from motor block. A double
blind, randomized controlled study was conducted in 46 parturients to determine
if a 30-mL normal saline bolus or sham administered via epidural approach after
delivery reduces the time to full motor recovery and the time to 2-dermatome
regression. No significant difference was found in time to full motor recovery
(saline group 83.18 +/- 54 minutes vs control group 100.23 +/- 48 minutes, P =
.27) or time to 2-dermatome sensory regression (saline group 29.32 +/- 16.35
minutes vs control group 36.14 +/- 14.39 minutes, P = .15). Results suggest no
advantage to the administration of a saline bolus after delivery to hasten the
motor recovery in parturients. A post hoc power analysis suggested a sample size
of 204 subjects would have been needed to show a difference for this dilute local
anesthetic regimen. There were no complications to the technique, which suggests
that it is safe to perform, but the difference in recovery (approximately 17
minutes) from a dilute local anesthetic dose may not be clinically significant.
PMID- 27501651
TI - Venous Thromboembolism Prophylaxis in Plastic Surgery: A Literature Review.
AB - Venous thromboembolism (VTE) is a major health concern because it increases
morbidity and mortality after a surgical procedure. A number of well-defined,
evidence-based guidelines are available delineating suitable use of prophylaxis
to prevent deep vein thrombosis and pulmonary embolism. Despite the available
literature, there are clear gaps between recommendations and clinical practice,
affecting the incidence of VTE. Plastic surgeons underuse the substantiated
literature and risk stratification tools that are available to decrease the
incidence of VTE in the office-based surgical setting because of fear of bleeding
or hematoma complications postoperatively. Venous thromboembolism creates an
economic burden on both the patient and the healthcare system. The intent of this
literature review is to determine existing VTE risk using assessment models
available to aid in the implementation of protocols for VTE prevention,
specifically for high-risk cosmetic surgical patients in office-based settings.
PMID- 27501652
TI - The Jehovah's Witness Population: Considerations for Preoperative Optimization of
Hemoglobin.
AB - Most members of the Jehovah's Witness community refuse blood transfusions, and
there are variations in what alternatives they will accept depending on their
personal decisions. To provide culturally competent care, healthcare providers
need to be knowledgeable about substitutions for blood administration as well as
the risks and benefits of available alternatives so that they can inform their
patients. It has been recognized in the literature that preoperative optimization
of hemoglobin levels with alternative treatment modalities through a
multidisciplinary approach can improve clinical outcomes in patients who refuse
blood products. The purpose of this article is to illuminate the current beliefs
of Jehovah's Witnesses regarding receiving blood products, discuss ethical and
legal considerations for the nurse anesthetist, discuss the risks of blood
transfusions, and examine transfusion alternatives. Finally, this article
considers a multidisciplinary approach to the optimization of preoperative
hemoglobin levels.
PMID- 27501653
TI - Anesthetic Considerations of Stiff-Person Syndrome: A Case Report.
AB - Stiff-person syndrome (SPS) is a neurologic disorder characterized by painful
involuntary episodes of severe muscle rigidity affecting the axial muscles and
extremities. Although the etiology of SPS is unknown, it is suspected to involve
the synthesis of gamma-aminobutyric acid (GABA). Symptoms of SPS are precipitated
by sudden unexpected movements, noises, and stress. Additionally, SPS has been
linked with various autoimmune disorders, including diabetes mellitus, thyroid
disease, pernicious anemia, and certain cancers. Because of the effect of SPS and
SPS medications, inhalational agents and neuromuscular blockers have the
potential to cause prolonged hypotonia following anesthesia, resulting in
respiratory failure despite full reversal of neuromuscular blockade. In
documented case reports, the outcomes of using general anesthesia with
inhalational agents and neuromuscular blockers in patients with SPS varied. This
case report highlights the anesthetic management of a 56-year-old woman with
diagnosed SPS undergoing a hemicolectomy for a colon mass using total intravenous
anesthesia.
PMID- 27501654
TI - Preventive Dorzolamide-Timolol for Rising Intraocular Pressure During Steep
Trendelenburg Position Surgery.
AB - The study purpose was to evaluate preventive use of dorzolamide-timolol
ophthalmic solution (Cosopt) during laparoscopic surgery with the patient in
steep Trendelenburg (ST) position. Periorbital swelling, venous congestion, and
elevated intraocular pressure (IOP) may produce low ocular perfusion. Prompt IOP
reduction is important because 30- to 40-minute episodes of acute IOP elevations
can result in retinal ganglion cell dysfunction. Dorzolamide-timolol ophthalmic
drops reduce IOP and may ameliorate this effect. A double-blind randomized
experimental study was conducted to test the effect of dorzolamide-timolol on IOP
elevation during laparoscopic surgeries in ST position. Patients were randomly
assigned to receive dorzolamide-timolol treatment or balanced salt solution
following anesthesia induction. The IOP levels were measured at baseline and 30
minutes intervals throughout surgery. The generalized estimating equations model
was used to analyze treatment and time effects and treatment by time
interactions. Ninety patients were recruited, with 46 receiving dorzolamide
timolol treatment and 44 receiving balanced salt solution. Statistical analysis
revealed significant treatment and time effects and treatment-time interactions
on IOP. Patients' IOP was significantly lower in the treatment group than
controls (P < .05 to P < .001). Treatment effects were medium to strong.
Prophylactic therapy with dorzolamide-timolol significantly reduced IOP of
surgical patients during ST positioning.
PMID- 27501655
TI - Unknown Pseudocholinesterase Deficiency in a Patient Undergoing TIVA with Planned
Motor Evoked Potential Monitoring: A Case Report.
AB - Pseudocholinesterase abnormalities are a genetic cause of aberrant metabolism of
the depolarizing muscle relaxant succinylcholine. This article examines a case
where succinylcholine was chosen to facilitate intubation due to its ultra short
duration and the request of the surgeon to monitor motor evoked potentials.
Following succinylcholine administration the neurophysiologist was unable to
obtain motor evoked potentials. This case study highlights the intraoperative and
postoperative management of an elderly patient with an unknown
pseudocholinesterase deficiency.
PMID- 27501656
TI - Tranexamic Acid in Anesthetic Management of Surgical Procedures.
AB - Blood loss during surgical procedures poses a grave risk to the patient, but
transfusion is costly and associated with adverse outcomes. Antifibrinolytics,
however, offer an economical and effective means of decreasing blood loss
associated with surgical procedures. Tranexamic acid (TXA) is an antifibrinolytic
that blocks lysine-binding sites of fibrinogen and fibrin, preventing the
breakdown of existing clots. This journal course reviews extensive research
demonstrating that antifibrinolytics such as TXA decrease blood loss and in some
studies reduce allogeneic transfusion requirements. In addition, this journal
course addresses concerns that use of antifibrinolytics increases embolic events,
reviews research that demonstrates TXA does not increase the incidence of
vascular occlusive events, and describes methods of TXA use in cardiac and
orthopedic surgical procedures, neurosurgery, and obstetrics. The Certified
Registered Nurse Anesthetist should consider the possibility, on a case-by-case
basis, of using TXA in surgical procedures to reduce blood loss with minimal
adverse effects.
PMID- 27501657
TI - [Laudatio on the prize of the Pflegezeitschrift 2015].
PMID- 27501658
TI - [Respectful communication in the nursing team].
PMID- 27501659
TI - [Nursing requires continuous language change.
PMID- 27501660
TI - [Nursing must retain its own language].
PMID- 27501661
TI - [No time - when pressure and stress increasingly dominate thinking, speaking and
nursing care].
PMID- 27501662
TI - ["But we only just want what's best for you!" - Subtle forms of coercion in
nursing].
PMID- 27501663
TI - [The language of youth in nursing].
PMID- 27501664
TI - [Psychological verbal communication in (psychiatric) nursing].
PMID- 27501665
TI - [Foreign nursing staff: quality assurance by reliable language tests].
PMID- 27501666
TI - [Eliminating minute nursing].
PMID- 27501667
TI - [Transcultural nursing: how different cultural concepts can influence your
nursing practice].
PMID- 27501668
TI - [Nursing anamnesis in theory and practice].
PMID- 27501669
TI - [Supporting parents in neonatology].
PMID- 27501670
TI - [Individual conflict resolution outside the confines of the legal system].
PMID- 27501671
TI - [Clarifying the goals of the research and selecting information sources].
PMID- 27501672
TI - [The intuitive interview].
PMID- 27501673
TI - [Nursing documentation disengaged from bureaucracy in ambulatory nursing
services].
PMID- 27501674
TI - [The project expert standards@work].
PMID- 27501675
TI - [The Role of Hydrogen Sulfide in Acute Liver Injury Induced by Traumatic Stress
in Rats].
AB - OBJECTIVE: To explore the role of hydrogen sulfide (H2S) in acute liver injury
induced by crushing hind limbs of rats. METHODS: The rats were randomly divided
into the following groups: control, crushing, H2S donor sodium hydrosulfide
(NaHS) + crushing, H2S inhibitor propargylglycine (PAG) + crushing group. The
acute liver injury model was established by 'crushing the hind limbs of rats with
standard weight. Rats were sacrificed at 30 min and 120 min after the crush. The
activities of serum aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) were measured by colorimetric method, and the content of H2S in plasma and
the contents of malondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the
liver and the activity of H2S generating enzyme (cystathionine y-lyase, CSE) were
determined by chemical method. The expression of CSE mRNA in liver was detected
by RT-PCR. RESULTS: For crush injury group, the levels of AST and ALT in serum,
MDA and protein carbonyl in liver increased. The levels of GSH, CSE, CSE mRNA in
liver and H2S in serum decreased. The administration of NaHS before limbs crush
could attenuate the changes of liver injury, but the pre-treatment with PAG could
exacerbate the changes. CONCLUSION: The decrease of H2S production could involve
in mediating the acute liver injury induced by traumatic stress in rats.
PMID- 27501676
TI - [Comparison of Postmortem MSCT and Autopsy Findings in Traffic Accident Victims].
AB - OBJECTIVE: To explore the application value of postmortem multi-slice spiral
computed tomography (MSCT) by observing and analyzing the injury features in the
traffic accident victims. METHODS: Ten traffic accident victims were scanned with
whole body MSCT. The systemic autopsy was subsequently performed to compare with
the results of MSCT. The advantages and disadvantages of autopsy and MSCT for
obtaining the information of traffic accident injuries were then analyzed.
RESULTS: MSCT could reveal 3D shape of fractures clearly and detect air
accumulation in different positions of the body, which showed the obvious
advantages compared with autopsy. However, the resolution of MSCT was limited
compared to the detection of organ and soft tissue injuries. CONCLUSION: A
combination of MSCT and autopsy is the best way for determining the manner and
the cause of death in traffic fatality victims.
PMID- 27501677
TI - [Relationship between Injury Time and Expressions of EPO and Its Receptors in
Rats Brain after Cerebral Injury].
AB - OBJECTIVE: To explore the relationship between injury age and expressions of
erythropoietin (EPO) and its receptor EPOR in the brain tissue of rats after
cerebral injury. METHODS: Seventy-two rats were randomly divided into control
group (36 rats) and cerebral injury group (36 rats). The rats were sacrificed at
1, 2, 4, 8, 12, 24 h after cerebral injury (6 rats at each time point) and the
brain tissues were extracted. The expressions of mRNA and protein of EPO and EPOR
at different time points were detected by real-time fluorescent quantitative PCR
and Western bloting. RESULTS: The expressions of EPO and EPOR increased within 24
h after injury. The expressions of mRNA and protein of EPO were related to the
injury age, and the correlations were 0.875, 0.911, respectively (P < 0.05). The
expressions of mRNA and protein of EPOR were related to the injury age, and the
correlation coefficients were 0.936, 0.905, respectively (P < 0.05). CONCLUSION:
The expressions of EPO and EPOR increase gradually in the early stage of the
rat's cerebral injury, which are associated with the injury age and could be a
useful value for estimating injury age.
PMID- 27501678
TI - [Expression of PTEN in Myocardial Tissue in Coronary Heart Disease].
AB - OBJECTIVE: To observe the expression of phosphatase and tensin homology deleted
on chromosome ten (PTEN) in myocardial tissue in patients with coronary heart
disease, and explore the relevance between the expression of PTEN and the
occurrence and development of coronary heart disease. METHODS: A total of 16
death cases with pathological diagnosis of coronary heart disease were collected
as experimental group, and 19 cases without myocardial lesions were selected as
control group. The expression of PTEN protein and its mRNA were detected by
immunohistochemistry and real-time fluorescence quantitative PCR respectively.
The correlation between the expression of PTEN and the pathogenesis of coronary
heart disease was analyzed. RESULTS: The expression of PTEN protein in myocardium
in cases with coronary heart disease was significantly lower compared with the
control group (P < 0.05). There was no statistical difference of the expression
of PTEN mRNA between experimental and control group (P > 0.05). CONCLUSION: PTEN
may be involved in the occurrence and development of coronary heart disease.
PMID- 27501679
TI - [Relationship between Body Height and Craniofacial Lines Measured by CT in
Southwest Han Males].
AB - OBJECTIVE: To establish regression model between craniofacial lines and body
height by measuring craniofacial lines in Southwest Han males using CT and to
accumulate data for the study of forensic anthropology. METHODS: Head CT data of
273 Han males in Southwest were collected and 7 craniofacial lines were
determined. Multiplanar reconstruction and volume rendering were performed by
image post-processing software and the selected lines were measured. The
relationship between each measuring indicator and body height was analyzed using
SPSS 21.0 software. The regression equation of body height estimation was
established and 50 samples were selected again and put into the mathematics
models to verify its accuracy. RESULTS: The linear regression equations of 7
lines were established (P < 0.05). The correlation coefficients of the unary
linear regression equations were 0.190-0.439 and the standard errors of the
estimate (SEE) were 4.597-5.023 cm. The correlation coefficients of the multiple
linear regression equation were 0.494-0.524 and the SEE were 4.418-4.458 cm. The
return tests showed that the highest +/- 1SEE accuracy of the multiple regression
equation: y = 83.959+3.589 x6+2.573 x2, were 30%; and the highest +/- 2SEE
accuracy of the multiple regression equation: y = 72.646+3.316 x6+1.586 x2+1.553
x4+2.211 x3, were 92%. CONCLUSION: There is significant linear correlation
between 7 selected lines and the stature in this study, and the plural linear
regression equation established could be applied for estimating the stature of
Southwest Han males.
PMID- 27501680
TI - [Personality Change due to Brain Trauma Caused by Traffic Accidents and Its
Assessment of Psychiatric Impairment].
AB - OBJECTIVE: To explore the main performance of personality change in people with
mild psychiatric impairments which due to the brain trauma caused by traffic
accidents and its value in assessment of psychiatric impairment. METHODS: The
condition of personality change of patients with traumatic brain injury caused by
traffic accident was evaluated by the Scale of Personality Change Post-traumatic
Brain Injury (SPCPTBI). Furthermore, the correlation between the personality
change and the degrees of traumatic brain injury and psychiatric impairment were
explored. Results In 271 samples, 239 (88.2%) with personality changes. Among
these 239 samples, 178 (65.7%), 46 (17.0%), 15 (5.5%) with mild, moderate and
severe personality changes, respectively. The ratio based on the extent of
personality changes to the degree of brain trauma was not significant (P > 0.05),
but the total score difference between the groups was significant (P < 0.05).
There was no statistical significance between the medium and high severity brain
trauma groups. The higher degree of personality changes, the higher rank of
mental disabilities. The total score difference of the scale of personality
change among the different mild psychiatric impairment group was significant
(P<0.05). The difference between other psychiatric impairment levels had
statistical significance (P < 0.05) except level 7 and 8. CONCLUSION: The
occurrence of personality change due to traumatic brain injury caused by traffic
accident was high. Correlations exist between the personality change and the
degree of psychiatric impairment. Personality change due to brain trauma caused
by traffic accident can be assessed effectively by means of SPCPTBI, and the
correlation between the total score and the extent of traumatic brain injury can
be found.
PMID- 27501681
TI - [Application of the Peak Area Ratio of STR Loci to Amelogenin Locus in the
Estimation of DNA Degradation].
AB - OBJECTIVE: To explore the change rules of peak area ratio of STR loci to
Amelogenin (AMEL) locus (STR/AMEL), a sex-determining gene in DNA degradation,
and to evaluate the application of STR/AMEL value in the estimation of DNA
degradation degree. METHODS: DNA was extracted from iliopsoas, and the variations
of STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) were analyzed after the
artificial degradation was made by DNase I, and the changes of these three ratios
of the iliopsoas naturally degraded in an outdoor environment were also analyzed.
The regression curves were analyzed using the periods of DNA degradation and
outside the body as the independent variable (x) and the STR/AMEL value as the
dependent variable (y) and three curve equations under two conditions were
established. RESULTS: Both under the conditions of artificial and natural
degradation, STR/AMEL value had a negative relationship with the degradation
time. The relationship between STR/AMEL and degradation time can be well
simulated by the cubic function. R2 was over 0.99 under controlled degradation
condition and over 0.86 under natural degradation condition. CONCLUSION: The
STR/AMEL value (Penta E/AMEL, Penta D/AMEL, FGA/AMEL) is negatively related with
the DNA degradation degree, which follows mathematical regression models
strictly, and it might be applied to evaluate the DNA degradation degree.
PMID- 27501682
TI - [Establishment and Verification of 6-color Fluorescent-labeled Rapid PCR
Amplification System].
AB - OBJECTIVE: To establish the rapid PCR amplification program and system and to
verify the technical indexes. METHODS: PCR multiplex and capillary
electrophoresis detection of 24 autosomal STR loci and one Y-STR loci using the 6
color fluorescence marking technology, as well as A melogenin and Y-InDel.
Meanwhile, sensitivity, specificity, identity, stability, mixing and a batch of
sample tests were investigated, and the genotype of various routine samples and
degraded, exfoliated cell samples were observed. RESULTS: The sensitivity of the
system was 0.062 5 ng. In addition, the genotype could be detected accurately
only around 65 min via rapid amplification. The species-specificity was high and
the genotyping of all kinds of dry blood specimens of filter paper and mixed,
degraded, exfoliated cell samples were accurate. CONCLUSION: The rapid
amplification system can significantly improve the detection rate, and obtain
accurate and stable genotyping results, which may be important implications for
the establishment of STR database and study on population genetics and forensic
identification.
PMID- 27501683
TI - Biomonitoring of 33 Elements in Blood and Urine Samples from Coastal Populations
in Sanmen County of Zhejiang Province.
AB - OBJECTIVE: To determine the normal reference values of 33 elements, Ag, Al, As,
Au, B, Ba, Be, Ca, Cd, Co, Cr, Cs, Cu, Fe, Ga, Hg, Li, Mg, Mn, Mo, Ni, Pb, Rb,
Sb, Se, Sr, Th, Ti, Tl, U, V, Zn and Zr, in the blood and urine samples from the
general population in Sanmen County of Zhejiang province, a typical coastal area
of eastern China. METHODS: The 33 elements in 272 blood and 300 urine samples
were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The
normality test of data was conducted using SPSS 17.0 Statistics. The data was
compared with other reports. RESULTS: The normal reference values of the 33
elements in the blood and urine samples from the general population in Sanmen
County were obtained, which of some elements were found to be similar with other
reports, such as Co, Cu, Mn and Sr, while As, Cd, Hg and Pb were generally found
to be higher than those previously reported. There was a wide variation between
the reports from different countries in blood Ba. CONCLUSION: The normal
reference values of the 33 elements in the blood and urine samples from the
general population in Sanmen County are established, and successfully applied to
two poisoning cases.
PMID- 27501684
TI - [A Retrospective Analysis of 88 Solved Intentional Homicide Cases].
AB - OBJECTIVE: To summarize the key points, difficulties and relevant practical
experiences for analyzing the scene of solved intentional homicide cases.
METHODS: The data of 88 solved intentional homicide cases in a county from 2004
to 2013 were collected and the retrospective analysis was performed. RESULTS: The
number of local female victims obviously higher than non-local female victims and
the number of non-local suspects is obviously higher than local suspects. The
number of Male suspects showed higher compared with the female. Most of them were
temporary workers, unemployment or farmers with less education backgrounds. The
main causes of victims' death were mechanical injury or asphyxia. The murders
were acquaintances in most intentional homicide cases. The motive of the stranger
murders was commonly money. The murder behavior types of homicide cases were
related with people, money and sexual assault. Camouflage and guilty behavior
showed the most significance. CONCLUSION: The accurate identification of suspects
is one of the most important task in forensic investigation and reflects the
importance of the criminal scene analysis for intentional homicide cases. It also
provides the direction of future research.
PMID- 27501685
TI - [Comparison of Different Pretreatment Methods for DNA Extraction from Teeth].
AB - OBJECTIVE: To compare the concentration of teeth DNA extracted by three different
pretreatment methods and to explore a simple, economical and practical
pretreatment method with high concentration of extracted DNA from teeth. METHODS:
A total number of 21 molars were collected from 7 corpses. The pretreatment of 3
molars from each individual was randomly performed by tooth crumb method, ball
milling method and liquid nitrogen milling method and 50 mg tooth crumb was
weight and DNA was extracted by AutoMate Express forensic DNA extraction system.
Subsequently, the concentration of DNA and corresponding STR genotyping of three
methods were compared. RESULTS: The DNA concentration extracted by tooth crumb
method, ball-milling method and liquid nitrogen milling method was 0.055 6-1.989
1 ng/MUL, 0.036 6-1.175 6 ng/MUL and 0.037 8-1.249 0 ng/MUL, respectively. The
DNA concentration obtained by tooth crumb method was higher (P < 0.05) and the
success rate of STR genotyping was high. CONCLUSION: Combined with AutoMate
Express forensic DNA extraction system, tooth crumb method is an efficient and
feasible method to extract DNA from teeth, which can be applied in forensic
practice.
PMID- 27501686
TI - [New Progress of MALDI-TOF-IMS in the Study of Proteomics].
AB - Matrix-assisted laser desorption/ionization time-of-flight imaging mass
spectrometry (MALDI-TOF-IMS) has been a classical technique for studying
proteomics in present and a tool for analyzing the distribution of proteins and
small molecules within biological tissue sections. MALDI-TOF-IMS can analyze
multiple unknown compounds in biological tissue sections simultaneously through a
single measurement which can obtain molecule imaging of the tissue while
maintaining the integrity of cellular and molecules in tissue. In recent years,
imaging mass spectrometry technique develops relatively quickly in all biomedical
domain. This paper based on the relevant data and reviews the present developing
level of MALDI-TOF-IMS, the principle of imaging mass spectrometry, methology and
the prospect in forensic pathology.
PMID- 27501687
TI - [Research Progress of circRNA and Its Significance in Forensic Science].
AB - RNA has received more attention in the field of forensic medicine and the
development of the new biological markers based on RNA shows great significance
in the analysis of complex cases. circular RNA (circRNA) is a kind of non-coding
RNA which is widely reported recently. Although the regulatory mechanisms of
generation and expression are not fully clear, the existing research indicates
that circRNA has important biological functions. CircRNA has a cell-type-specific
expression with great stability and a high expression level, which makes it
meaningful in forensic applications potentially. In this paper, the research
progress, the generation and regulation of circRNA as well as its biological
characteristics and functions are summarized, which will provide references for
related studies and forensic applications.
PMID- 27501688
TI - Development of a fast and low-cost qPCR assay for diagnosis of acute gas
pharyngitis.
AB - BACKGROUND: Group A streptococci (GAS) are the most common bacterial cause of
acute pharyngitis and account for 15-30 % of cases of acute pharyngitis in
children and 5-10 % of cases in adults. In this study, a real-time quantitative
PCR (qPCR) based GAS detection assay in pharyngeal swab specimens was developed.
METHODS: The qPCR assay was compared with the gold standard bacterial culture and
a rapid antigen detection test (RADT) to evaluate its clinical performance in 687
patients. The analytical sensitivity of the assay was 240 cfu/swab. Forty-five
different potential cross-reacting organisms did not react with the test. Four
different laboratories for the reproducibility studies were in 100 % (60/60)
agreement for the contrived GAS positive and negative swab samples. RESULTS: The
relative sensitivities of the RADT and the qPCR test were 55.9 and 100 %; and the
relative specificities were 100 and 96.3 %, respectively. Duration of the total
assay for 24 samples including pre-analytical processing and analysis changed
between 42 and 55 min depending on the type of qPCR instrument used. A simple DNA
extraction method and a low qPCR volume made the developed assay an economical
alternative for the GAS detection. CONCLUSION: We showed that the developed qPCR
test is rapid, cheap, sensitive and specific and therefore can be used to replace
both antigen detection and culture for diagnosis of acute GAS pharyngitis.
PMID- 27501689
TI - Is psychometrics science?
PMID- 27501690
TI - Construction of high-resolution genetic maps of Zoysia matrella (L.) Merrill and
applications to comparative genomic analysis and QTL mapping of resistance to
fall armyworm.
AB - BACKGROUND: Zoysia matrella, widely used in lawns and sports fields, is of great
economic and ecological value. Z. matrella is an allotetraploid species (2n = 4x
= 40) in the genus zoysia under the subfamily Chloridoideae. Despite its
ecological impacts and economic importance, the subfamily Chloridoideae has
received little attention in genomics studies. As a result, limited genetic and
genomic information are available for this subfamily, which have impeded progress
in understanding evolutionary history of grasses in this important lineage. The
lack of a high-resolution genetic map has hampered efforts to improve zoysiagrass
using molecular genetic tools. RESULTS: We used restriction site-associated DNA
sequencing (RADSeq) approach and a segregating population developed from the
cross between Z. matrella cultivars 'Diamond' and 'Cavalier' to construct high
resolution genetic maps of Z. matrella. The genetic map of Diamond consists of
2,375 Single Nucleotide Polymorphism (SNP) markers mapped on 20 linkage groups
(LGs) with a total length of 1754.48 cM and an average distance between adjacent
markers at 0.74 cM. The genetic map of Cavalier contains 3,563 SNP markers on 20
LGs, covering 1824.92 cM, with an average distance between adjacent markers at
0.51 cM. A higher level of genome collinearity between Z. matrella and rice than
that between Z. matrella and sorghum was revealed by comparative genomic
analysis. Pairwise comparison revealed that two independent nested chromosome
fusion events occurred after Z. matrella and sorghum split from a common
ancestor. The high-resolution linkage maps were applied into mapping QTLs
associated with fall armyworm (FAW) resistance and six loci located on LGs 8 and
20 were detected to be significantly associated with FAW resistance. CONCLUSION:
The high-resolution linkage maps provide anchor points for comparative genomics
analysis between Z. matrella and other grass species. Our comparative genomic
analysis suggested that the chromosome number reduction from 12 to 10 had
occurred independently via a single-step in the subfamilies Chloridoideae and
Panicoideae. The high-resolution genetic maps provide an essential framework for
mapping QTLs associated with economically and agronomically important traits. The
major QTLs mapped on LG8 of the Cavalier map provide a starting point for cloning
FAW resistance genes and further studies for a better understanding of FAW
resistance in zoysiagrass.
PMID- 27501691
TI - Effects of procurement practices on quality of medical device or service
received: a qualitative study comparing countries.
AB - BACKGROUND: We know little about how procurement of a high-risk medical device
(HRMD) affects clinical practice and outcomes. In health systems in high-income
countries, and specifically those that maintain a national arthroplasty registry,
procurement decisions are frequently guided by long-term clinical results, with
the goal of ensuring at least standard quality of HRMDs. But in countries like
Mexico, decision-making is often dominated by lowest acquisition price. We set
out to study the impact of procurement for orthopaedic HRMDs on clinical
procedures and outcomes. METHODS: We based our qualitative study on 59 in-depth
interviews with stakeholders from Mexico, Switzerland, Germany, and UK:
orthopaedic specialists, government officials, other experts, and social security
system managers or administrators. We took a healthcare delivery approach to
capturing and comparing factors that affected the regulations of HRMDs and
procurement processes, and to understanding connections between procurement and
clinical practice. RESULTS: Our findings demonstrate for procurement processes
that the three European countries compared to Mexico don't have similar concerns
with regards to their procurement processes. Deficiencies of procurement
regulations and practices identified from representatives in Mexico were almost
absent in European countries. We identified three areas of deficiency: 1) HRMD
regulations based on insufficiently robust clinical evidence (mainly noted by
European countries); 2) Follow-up on Health Technology Assessments is inadequate
(noted by Mexico) and methodology not always good enough (noted by European
countries); and, 3) Lowest-acquisition price often guides procurement decisions
and thus may not align with needs of clinical procedures (noted by Mexico and
some European countries). CONCLUSIONS: Procurement processes for orthopaedic
HRMDs may have an impact on clinical procedures and outcomes. A favourable
approach is one where orthopaedic specialists are parties to the procurement
process, and post-market surveillance data informs decision-making. Actors in the
procurement process can improve their impact on clinical procedures and outcomes
by developing specific strategies that better align the needs of both,
procurement and clinical procedures.
PMID- 27501692
TI - Intravascular ultrasound for transcatheter paravalvular leak closure.
AB - Transcatheter closure of paravalvular leaks requires precise assessment of the
location, size, and shape of the defect. Transesophageal echocardiography plays
an important role in this process. We encountered a case of a paravalvular leak
at the aortic position after aortic and mitral valve replacement. It was
impossible to detect the precise location of the paravalvular leak with
transesophageal echocardiography because of an acoustic shadow from the mitral
mechanical valve. Intraoperative use of intravascular ultrasound was useful for
determining the morphology of the defect and evaluating the procedure during the
operation.
PMID- 27501693
TI - Surgical decision making for revascularization of chronically occluded right
coronary artery.
AB - OBJECTIVE: Chronic totally occluded right coronary artery (CTO-RCA) often poses a
problem in decision making for/against bypass grafting due to the lack of
standardized indication criteria. The aim of the study was to investigate whether
qualitative angiograms can be useful in decision making for/against surgical
revascularization of CTO-RCA. METHODS: A retrospective cohort study was conducted
with 69 patients who underwent elective CABG procedure, including single graft to
the RCA. The distal run-off of the bypassed RCA was measured intraoperatively
using the ultrasonic transit-time method. As a primary endpoint of the study, the
flow values were analysed in regard to diameter of the recipient artery. As a
secondary endpoint, the correlations between the regional and global LV function,
Rentrop grading, type of collateral pathway, number of donor sources,
comorbidity, and the graft flow and the diameter of the recipient artery were
investigated using uni- and multi-variate regression analyses. RESULTS: In
general, the flow values correlated significantly with the diameter of the
recipient artery. Significantly lower flow (p < 0.0001) and diameter values (p <
0.05) were found in hypo/akinetic and infarcted area reflecting functionality of
the CTO-RCA territory. CONCLUSIONS: The qualitative angiograms combined with
regional wall motion studies can be useful in decision making for
revascularization of CTO-RCA. Revascularization of akinetic/infarcted CTO-RCA
territory is associated with lower graft flows even in patients presented with
high Rentrop class and high degree of collaterality, suggesting necessity of
viability tests prior to bypass surgery.
PMID- 27501696
TI - Clinical severity in forecasting platelet to lymphocyte ratio in Crimean-Congo
hemorrhagic fever patients.
AB - Crimean-Congo hemorrhagic fever (CCHF) is a life-threatening disease that
develops as a result of infection by a member of the Nairovirus genus of the
Bunyaviridae family, and its initial symptoms are not specific. In patients with
severe clinical progression, in particular, the neutrophil rate is high, whereas
lymphocyte and monocyte levels are low. A total of 149 patients, in whom the
diagnosis was confirmed with reverse transcriptase PCR, were included in the
study. In order to compare patient clinical progression severity, we divided the
patients into two groups. For group 1, Cevik's severity score was used. The
patients who had a platelet/lymphocyte ratio (PLR) <41 constituted group 2. Of
149 patients, 20 (13.4 %) were determined as group 1 (Cevik's classification) and
38 (25.5 %) were determined as group 2 (PLR <41). Of 11 deaths, 4 (36.4 %)
patients were from group 1 and 7 (63.6 %) were from group 2. This is the first
study to our knowledge to analyse the relationship between severity and PLR in
patients with CCHF. PLR is a simple laboratory test that can aid in determining
the prognosis of individuals with this disease.
PMID- 27501695
TI - Development of an annually updated Japanese national clinical database for chest
surgery in 2014.
AB - OBJECTIVES: A national clinical database (NCD) adopted an "Internet-based
collection" in 2011. An NCD specializing in chest surgery was launched based on
the NCD system in 2014. The system was linked to the board certification as the
second level in the hierarchy of the specialty of chest surgery and accreditation
of educational institutions for chest surgery. Here, we report the status of the
NCD for chest surgery in 2014 and clarified its registration rate and its
accuracy. METHODS: Chest surgeries undertaken in Japan since January 1st, 2014
until the end of the same year were registered through an Internet-based system
until April 8th, 2015. The registration rate was compared with the annual survey
conducted by the Japanese Association for Thoracic Surgery (JATS) from 2011 to
2014. The rate of accurate inputting was measured by an Internet-based audit in
reference to 563 anonymous operative notes of patients presented by 106 chest
surgeons at the time of renewal for board certification for chest surgery.
RESULTS: A total of 88,112 chest-surgical procedures were registered from 1000
chest surgery units (CSUs). Distribution of procedures by thoracic disease was
almost identical to that of the annual survey conducted by JATS. However, the NCD
had 4260 more registered procedures compared with the annual survey. The Internet
based audit showed that inter-rater agreement between Internet-based data and
operative notes in any item was >94 %. CONCLUSIONS: The NCD system can
sustainably provide important and up-to-date information relating to preoperative
status, oncology, and best practice for chest surgery in Japan.
PMID- 27501694
TI - Optimal temperature management in aortic arch operations.
AB - Hypothermic circulatory arrest is a critical component of aortic arch procedures,
without which these operations could not be safely performed. Despite the use of
hypothermia as a protective adjunct for organ preservation, aortic arch surgery
remains complex and is associated with numerous complications despite years of
surgical advancement. Deep hypothermic circulatory arrest affords the surgeon a
safe period of time to perform the arch reconstruction, but this interruption of
perfusion comes at a high clinical cost: stroke, paraplegia, and organ
dysfunction are all potential-associated complications. Retrograde cerebral
perfusion was subsequently developed as a technique to improve upon the rates of
neurologic dysfunction, but was done with only modest success. Selective
antegrade cerebral perfusion, on the other hand, has consistently been shown to
be an effective form of cerebral protection over deep hypothermia alone, even
during extended periods of circulatory arrest. A primary disadvantage of using
deep hypothermic circulatory arrest is the prolonged bypass times required for
cooling and rewarming which adds significantly to the morbidity associated with
these procedures, especially coagulopathic bleeding and organ dysfunction. In an
effort to mitigate this problem, the degree of hypothermia at the time of the
initial circulatory arrest has more recently been reduced in multiple centers
across the globe. This technique of moderate hypothermic circulatory arrest in
combination with adjunctive brain perfusion techniques has been shown to be safe
when performing aortic arch operations. In this review, we will discuss the
evolution of these protection strategies as well as their relative strengths and
weaknesses.
PMID- 27501697
TI - Validation of T1 and T2 algorithms for quantitative MRI: performance by a vendor
independent software.
AB - BACKGROUND: Determination of the relaxation time constants T1 and T2 with
quantitative magnetic resonance imaging is increasingly used for both research
and clinical practice. Recently, groups have been formed within the Society of
Cardiovascular Magnetic Resonance to address issues with relaxometry. However, so
far they have avoided specific recommendations on methodology due to lack of
consensus and current evolving research. Standardised widely available software
may simplify this process. The purpose of the current study was to develop and
validate vendor-independent T1 and T2 mapping modules and implement those in the
versatile and widespread software Segment, freely available for research and FDA
approved for clinical applications. RESULTS: The T1 and T2 mapping modules were
developed and validated in phantoms at 1.5 T and 3 T with reference standard
values calculated from reference pulse sequences using the Nelder-Mead Simplex
optimisation method. The proposed modules support current commonly available MRI
pulse sequences and both 2- and 3-parameter curve fitting. Images acquired in
patients using three major vendors showed vendor-independence. Bias and
variability showed high agreement with T1 and T2 reference standards for T1
(range 214-1752 ms) and T2 (range 45-338 ms), respectively. CONCLUSIONS: The
developed and validated T1 and T2 mapping and quantification modules generated
relaxation maps from current commonly used MRI sequences and multiple signal
models. Patient applications showed usability for three major vendors.
PMID- 27501698
TI - A Prospective Examination of the Relations Between Emotional Abuse and Anxiety:
Moderation by Distress Tolerance.
AB - Anxiety, the most common and impairing psychological problem experienced by
youth, is associated with numerous individual and environmental factors. Two such
factors include childhood emotional abuse (CEA) and low distress tolerance (DT).
The current study aimed to understand how CEA and low DT impacted anxiety
symptoms measured annually across 5 years among a community sample of youth. We
hypothesized DT would moderate the relationship between CEA and anxiety, such
that youth with higher levels of CEA and lower levels of DT would have elevated
anxiety over time. Community youth (N = 244) were annually assessed across 5
years using the Revised Child Anxiety and Depression Scale, Childhood Trauma
Questionnaire, and Behavioral Indicator of Resiliency to Distress. Higher CEA at
baseline was associated with higher anxiety at baseline, higher anxiety at each
annual assessment, and with greater overall decreases in anxiety over time. Lower
DT was associated with higher anxiety at baseline, but did not predict changes in
anxiety over time. Baseline DT significantly moderated the relationship between
baseline CEA and anxiety, such that youth with both higher CEA and lower DT had
the highest anxiety at each annual assessment. Youth with lower DT and higher CEA
scores had the highest level of anxiety symptoms across time.
PMID- 27501699
TI - A unique method for estimating the reliability learning curve of optic nerve
sheath diameter ultrasound measurement.
AB - BACKGROUND: Optic nerve sheath diameter (ONSD) measurement using ultrasound has
been proposed as a rapid, non-invasive, point of care technique to estimate intra
cranial pressure (ICP). Ultrasonic measurement of the optic nerve sheath can be
quite challenging and there is limited literature surrounding learning curves for
this technique. We attempted to develop a method to estimate the reliability
learning curve for ONSD measurement utilizing a unique definition of reliability:
a plateau in within-subject variability with unchanged between-subject
variability. METHODS: As part of a previously published study, a single operator
measured the ONSD in 120 healthy volunteers over a 6-month period. Utilizing the
assumption that the four measurements made on each subject during this study
should be equal, the relationship of within-subject variance was described using
a quadratic-plateau model as assessed by segmental polynomial (knot) regression.
RESULTS: Segmental polynomial (knot) regression revealed a plateau in within
subject variance after the 21st subject. However, there was no difference in
overall mean values [3.69 vs 3.68 mm (p = 0.884)] or between-subject variance
[14.49 vs 11.92 (p = 0.54)] above or below this cutoff. CONCLUSIONS: This study
suggests a significant finite learning curve associated with ONSD measurements.
It also offers a unique method of calculating the learning curve associated with
ONSD measurement.
PMID- 27501700
TI - Lung ultrasound in internal medicine: training and clinical practice.
AB - BACKGROUND: Lung ultrasound (LUS) represents an emerging technique for bedside
chest imaging in different clinical settings. A standardized approach allows the
diagnosis, the quantification, and the follow-up of different conditions for
which acute respiratory failure is the main clinical presentation. The aim of
this study was to test what skill targets could be achieved in LUS, with a short
training course offered to 19 Medical Doctors attending the certification board
school in Internal Medicine at the University of Verona, Italy. METHODS: The
training course (theoretical and practical) consisted of 9 h subdivided in 4
days. Each trainee examined three healthy volunteers during the first day that
was also the day of the theoretical lessons. Moreover, they examined nine
patients per day (a total of 27 patients). Trainees were tested in the
recognition of the basic signs in LUS, the managing of the Bedside Lung
Ultrasound Evaluation (the BLUE protocol), and the recognition of the broad
clinical scenarios recognized by the LUS. Kappa statistic was used to calculate
the inter-observer agreement (trainees/tutor). RESULTS: Twenty-seven patients
were examined by the 19 trainees (ten trainees had previous limited experience in
general ultrasound). The agreement among the trainees and the tutor in the
recognition of the LUS basic signs and in the recognition of the BLUE protocol
profiles ranged from "fair" to "excellent". In particular, the agreement among
the trainees and the tutor in the final LUS diagnosis was "excellent" for the
recognition of the interstitial syndrome and the pleural effusion, "substantial"
for the recognition of the normal lung, and "moderate" for the recognition of
consolidation and pneumothorax. LUS outcome gave useful information and drove
change in therapy in 16 patients. It affected immediate management in nine
patients. The concordance between the previous X chest ray and LUS was observed
in 21 patients. CONCLUSIONS: A short training in LUS provided good proficiency in
the recognition only of the main signs of the BLUE protocol, but allowed a
correct LUS diagnosis in the Internal Medicine most frequent clinical settings of
acute respiratory failure. This study supports incorporating LUS into Internal
Medicine fellowship training programs.
PMID- 27501701
TI - Orthogeriatric co-management improves the outcome of long-term care residents
with fragility fractures.
AB - BACKGROUND: Fragility fractures are a major health care problem worldwide. Both
hip and non-hip fractures are associated with excess mortality in the years
following the fracture. Residents of long-term nursing homes represent a special
high-risk group for poor outcomes. Orthogeriatric co-management models of care
have shown in multiple studies to have medical as well as economic advantages,
but their impact on this high-risk group has not been well studied. OBJECTIVE: We
studied the outcome of long-term care residents with hip and non-hip fractures
admitted to a geriatric fracture center. METHODS: The study design is a single
center, prospective cohort study at a level-I trauma center in Austria running a
geriatric fracture center. The cohort included all fragility fracture patients
aged over 70 admitted from a long-term care residence from May 2009 to November
2011. The data set consisted of 265 patients; the mean age was 86.8 +/- 6.7
years, and 80 % were female. The mean follow-up after the index fracture was 789
days, with a range from 1 to 1842 days. Basic clinical and demographic data were
collected at hospital admission. Functional status and mobility were assessed
during follow-up at 3, 6, and 12 months. Additional outcome data regarding
readmissions for new fractures were obtained from the hospital information
database; mortality was crosschecked with the death registry from the
governmental institute of epidemiology. RESULTS: 187 (70.6 %) patients died
during the follow-up period, with 78 patients (29.4 %) dying in the first year.
The mean life expectancy after the index fracture was 527 (+/-431) days.
Differences in mortality rates between hip and non-hip fracture patients were not
statistically significant. Compared to reported mortality rates in the
literature, hip fracture patients in this orthogeriatric-comanaged cohort had a
significantly reduced one-year mortality [OR of 0.57 (95 % CI 0.31-0.85)]. After
adjustment for confounders, only older age (OR 1.091; p = 0.013; CI 1.019-1.169)
and a lower Parker Mobility Scale (PMS) (OR 0.737; p = 0.022; CI 0.568-0.957)
remained as independent predictors. During follow-up, 62 patients (23.4 %)
sustained at least one subsequent fracture, and 10 patients (3.4 %) experienced
multiple fractures; 29 patients (10.9 %) experienced an additional fracture
within the first year. Nearly, half (47.1 %) regained their pre-fracture mobility
based on the PMS. CONCLUSION: Despite the generally poor outcomes for fragility
fracture patients residing in long-term care facilities, orthogeriatric co
management appears to improve the outcome of high-risk fragility fracture
patients. One-year mortality was 29.4 % in this cohort, significantly lower than
in comparable trials. Orthogeriatric co-management may also have positive impacts
on both functional outcome and the risk of subsequent fractures.
PMID- 27501702
TI - Better satisfaction of patients operated on anterior cruciate ligament
reconstruction in outpatient setting. A prospective comparative monocentric study
of 60 cases.
AB - INTRODUCTION: The purpose of this study was to compare satisfaction, clinical
scores, and complications of patients operated on anterior cruciate ligament
reconstruction (ACLR) in outpatient setting compared to patients operated in the
conventional hospitalization. PATIENTS AND METHODS: This prospective non
randomized study compared 30 patients (mean age 31 +/- 9 years) operated on
outpatient setting for an isolated ACLR matched 1:1 according to age, gender,
body mass index, delay to surgery, and preoperative clinical score (IKDC) to 30
patients operated for an ACLR in our conventional hospitalization department
during the same period. All the patients were operated on by the same surgeon.
The same technique of anterior cruciate ligament reconstruction with using four
bundles semitendinosus and cage fixation was used. The same anaesthesiologic
protocol and perioperative cares were used in all patients. Patients'
satisfaction was assed using five questions about the course of surgery and
hospitalization and a four-level satisfaction questionnaire (excellent, good,
fair, and poor). Clinical scores (IKDC and KOOS) were compared preoperatively and
at 1 year. Readmission within 30 day and complications at 1 year were compared in
both groups. RESULTS: Satisfaction was significantly better in the group of day
case surgery and more patients of the group day-case surgery recommended this
modality of treatment (29 against 24; p = 0.04). The IKDC score improved in the
two groups (day-case group from 64 +/- 17 to 86 +/- 7; p < 0.001; conventional
hospitalization from 60 +/- 21 to 85 +/- 10; p < 0.001), but no significant
difference between two groups was found at 1 year (p = 0.86). No readmission was
necessary in the two groups, but two revisions were needed in the group of the
conventional hospitalization. CONCLUSIONS: Results of our study showed that
patients operated on day-case surgery for an isolated ACLR presented a higher
rate of satisfaction compared to patients operated in the conventional
hospitalization with comparable clinical results at 1 year. LEVEL OF EVIDENCE:
Level III, comparative study.
PMID- 27501703
TI - Significant differences in femoral torsion values depending on the CT measurement
technique.
AB - INTRODUCTION: This study compared the feasibility of six different CT-based
measurement techniques for establishing an indication for derotational osteotomy
in the cases of patellar instability or femoral fracture. MATERIALS AND METHODS:
CT scans of 52 single human cadaver femora were measured using six different
torsion measurement techniques (described by Waidelich, Murphy, and Yoshioka on
transverse images and Hernandez, Jarrett, and Yoshioka on oblique images). All
measurements were performed by four observers twice to assess intraobserver and
interobserver agreement. The intraclass correlation coefficient (ICC), ANOVA, and
Bonferroni post hoc test were used for the statistical analysis. RESULTS:
Significant differences (P < 0.001) between the values for femoral torsion were
observed with all techniques except Yoshioka's techniques on transverse and
oblique slices (P = 1.000) (transverse images: Waidelich 22.4 degrees +/- 6.8
degrees , Murphy 17.5 degrees +/- 7.0 degrees , Yoshioka 13.4 degrees +/- 6.9
degrees ; oblique images: Hernandez 11.4 degrees +/- 7.4 degrees , Jarrett 14.9
degrees +/- 7.5 degrees , Yoshioka oblique 13.4 degrees +/- 7.1 degrees ).
Intraobserver and interobserver agreement showed a high level of reproducibility
(ICC 0.877-0.986; mean 0.8 degrees -2.9 degrees ) for all techniques, with the
greatest difference being observed with Hernandez's technique (11.4 degrees /10
degrees ). CONCLUSIONS: Femoral torsion values depend on the measurement
technique. When derotational osteotomy is being considered, it is essential to
use different threshold values depending on the measurement technique.
PMID- 27501704
TI - Management of shoulder instability: the current state of treatment among German
orthopaedic surgeons.
AB - INTRODUCTION: The aim of this study was to evaluate the current state of
treatment in traumatic anterior shoulder dislocation in Germany and to detect
changes over the last 12 years. METHODS: Seven hundred ninety-six trauma and/or
orthopaedic departments were found in the German hospital directory 2012. The
websites of each department were searched for the email address of the
responsible shoulder surgeon (if applicable) or the head of the department. Seven
hundred forty-six email addresses were found, and emails with the request to
participate in an online survey were sent in January 2013. Six hundred seventy
five emails probably reached the correct addressee. Seventy-one emails were
rejected, and no contact could be made. One-hundred ninety-one (28 %)
participated in the study. The data were compared to similar data from a survey
on shoulder dislocation performed in the same department and published in 2001.
RESULTS: After the first-time traumatic shoulder dislocation in patients aged
younger than 30 years participating in sports, 14 % of the participants would
prefer conservative treatment, 83 % arthroscopic, and 3 % open surgery. When
surgery was indicated, arthroscopic Bankart repair was the treatment of choice
for 93 % of the participants. In 2001, 27 % had indicated conservative treatment
after the first-time shoulder dislocation in active patients younger than 30
years. When surgery was indicated, 66 % had performed arthroscopic and 34 % open
stabilization. For the standard arthroscopic Bankart repair without concomitant
injuries, 41 % of the participants use two and 54 % three suture anchors.
Knotless anchors were preferred by 72 %. In the case of glenoid bone loss greater
than 25 %, only 46 % perform a procedure for glenoid bone augmentation. Fifteen
percent of the participants always recommended immobilization in external
rotation after traumatic first-time shoulder dislocation. CONCLUSIONS: The
majority of participants recommend arthroscopic Bankart repair with two or three
suture anchors in young persons with the first-time dislocations. Compared to
2001 less recommend conservative treatment, complex "open" surgical procedures
are no longer used. The knowledge that a Bankart procedure likely fails in
significant glenoid bone loss is not implemented in the clinical practice. Thus,
there is a need to educate surgeons on this topic.
PMID- 27501705
TI - One-year development of QOL following orthopaedic polytrauma: a prospective
observational cohort study of 53 patients.
AB - INTRODUCTION: Most studies of polytrauma examined highly mixed patient groups.
The objective of the present study was to report the development of patient
reported quality of life (QOL), in a patient group with musculoskeletal
polytrauma, excluding patients with major thoracic, abdominal, and brain
injuries. MATERIALS AND METHODS: The study design was a 1-year cohort follow-up
study. Recordings of injury severity were measured with the ISS and NISS. Patient
reported QOL was measured with the questionnaires Eq5d-5L and SF-36 and compared
to age-matched reference populations. Moreover, patients return to work status
was measured. Data were collected prospectively at discharge, 3, 6, and 12
months. RESULTS: 53 patients were included. The mean age was 42.3 years, ranging
from 17 to 78 years. Twelve months after trauma admission, the mean Eq5d-5L index
was 0.601 (95 % CI 0.546-0.657). A progressive increasing Eq5d-5L index and SF-36
PCS was observed between the discharge and the 12-month follow-up (p < 0.001).
The development in QOL from 6 to 12 months almost shows identically scores.
Throughout the study period, patients reported significant worse QOL compared
with the established reference population. 32 % of patients have resumed earlier
employment status at 1-year follow-up. CONCLUSIONS: Throughout the 12-month
observational period, patients reported worse QOL compared to the age-matched
reference population. The development of QOL from 6- to 12-month time points
almost showed identically scores with only little improvement. At the end of 1
year follow-up, 32 % of patients had resumed prior employment status.
PMID- 27501706
TI - Effect of Laminin on Neurotrophic Factors Expression in Schwann-Like Cells
Induced from Human Adipose-Derived Stem Cells In Vitro.
AB - The Schwann-like cells can be considered as promising in stem cell therapies, at
least in experimental models. Human adipose-derived stem cells (ADSCs) are
induced into Schwann-like cells (SC-like cells) and are cultured on either a
plastic surface or laminin-coated plates. The findings here reveal that laminin
is a critical component in extracellular matrix (ECM) of SC-like cells at in
vitro. The survival rate of SC-like cells on a laminin matrix are measured
through MTT assay and it is found that this rate is significantly higher than
that of the cells grown on a plastic surface (P < 0.05). Schwann cell markers and
the myelinogenic ability of SC-like cells at the presence versus absence of
laminin are assessed through immunocytochemistry. The analysis of GFAP/S100beta
and S100beta/MBP markers indicate that laminin can increase the differentiated
rate and myelinogenic potential of SC-like cells. The expression levels of SCs
markers, myelin basic proteins (MBP), and neurotrophic factors in two conditions
are analyzed by real-time reverse transcription polymerase chain reaction (RT
PCR). The findings here demonstrated that gene expression of SCs markers, MBP,
and brain-derived neurotrophic factors (BDNF) increase significantly on laminin
compared to plastic surface (P < 0.01). In contrast, the nerve growth factor
(NGF) expression is downregulated significantly on laminin-coated plates (P <
0.05). The obtained data suggest that production of neurotrophic factors in SC
like cell in presence of laminin can induce appropriate microenvironment for
nerve repair in neurodegenerative diseases.
PMID- 27501707
TI - Dihydromyricetin Ameliorates 3NP-induced Behavioral Deficits and Striatal Injury
in Rats.
AB - Oxidative stress is closely involved in neurodegenerative diseases. The present
study aimed to examine the effect of anti-oxidant DHM (dihydromyricetin) on 3NP
(3-nitropropionic acid) -induced behavioral deficits of experimental rats and
striatal histopathological injury by using behavioral, imaging, biochemistry,
histochemistry and molecular biology technologies. The experimental results
showed that both motor dysfunctions and learning and memory impairments induced
by 3NP were significantly reduced after DHM treatment. 3NP-induced striatal
metabolic abnormality was also remarkably improved by DHM treatment, showed as
the increased glucose metabolism in PET/CT scan, decreased MDA (malondialdehyde)
and increased SOD (superoxide dismutase) activity in enzyme histochemical
staining. In addition, the cell apoptosis was evidently detected in the striatum
of the 3NP group, while in the 3NP + DHM group, the number of apoptotic cells was
remarkably reduced. 3NP treatment obviously induced down-regulation of Bcl-2, and
up-regulations of Bax and Cleaved Caspase-3, while these changes were
significantly reversed by DHM treatment. The present results suggested that DHM
showed its protective effect by anti-oxidant and anti-apoptosis mechanisms.
PMID- 27501708
TI - Nipple Preservation in Breast Cancer Associated with Nipple Discharge.
AB - BACKGROUND: Breast carcinoma presented with nipple discharge is a rare condition.
There is theoretical concern about preserving nipple in these patients since the
risk of nipple-areolar complex involvement may be greater, but not many studies
in the literature have addressed on this issue. The aim of the current study was
to determine the incidence and outcome of nipple preservation in breast cancer
associated with nipple discharge. METHODS: Medical records of patients who were
diagnosed to have breast carcinoma and presented with nipple discharge from May
2009 to October 2014 were retrospectively reviewed. RESULTS: Sixty patients
presented with nipple discharge were diagnosed with breast cancer, which
represent 3.8 % of all patients who underwent breast cancer surgery in our unit
during the study period. Forty-six patients (76.7 %) had nipple discharge as
their only symptom, while the rest also presented with breast mass clinically or
radiologically. All patients had mammogram and ultrasound performed, and 53.3 and
63.3 % respectively showed suspicious findings. Forty-one out of 46 (89.1 %)
nipple discharge cytology were inadequate or benign. Thirty-two microdochectomy
were performed. Routine frozen section was utilized intra-operatively to ensure
clear margins. The most common histology was ductal carcinoma in situ (DCIS) (n =
29, 48.3 %), followed by DCIS with invasive ductal carcinoma (n = 23, 38.3 %).
Regarding treatment, 26 patients (43.3 %) had nipple preserved, including 21
breast conservative surgery and five nipple-sparing mastectomies. Overall, no
local or systemic recurrence was observed at a median follow-up of 27 months. Ten
out of 34 (29.4 %) mastectomy specimens showed NAC involvement on pathology. By
comparing patients with NAC preserved to patients with NAC removed, no
significant preoperative predictors were identified. CONCLUSION: Breast carcinoma
patients who present with nipple discharge usually have early-stage cancer.
Presence of nipple discharge is not equivalent to NAC involvement. Nipple
preservation can be oncologically safe if negative margins are ascertained.
PMID- 27501709
TI - The Role of Troponin in Blunt Cardiac Injury After Multiple Trauma in Humans.
AB - BACKGROUND: The incidence of cardiac injury in immediate fatalities after blunt
trauma remains underestimated, and reliable diagnostic strategies are still
missing. Furthermore, clinical data concerning heart-specific troponin serum
levels, injury severity score (ISS), catecholamine treatment and survival of
patients on admission to the hospital have rarely been interrelated so far.
Therefore, the object of the present study was to identify predictive parameters
for mortality in the context of blunt cardiac injury. METHODS: This retrospective
observational study included 173 severely injured patients with an ISS >=25
admitted to the University Hospital of Ulm, a level 1 trauma center, during 2009
2013 . Furthermore, 83 blunt trauma victims who died before hospital admission
were subjected to postmortem examination at the Institute of Legal Medicine,
University of Ulm, during 2009-2014. ISS, cardiac injury and associated thoracic
injuries were determined in both groups. Furthermore, in the hospitalized
patients, serum troponin and IL-6 levels were measured. RESULTS: Macroscopic
heart injury was observed in 18 % of the patients who died at the scene and only
in 1 % of the patients admitted to the hospital, indicating that macroscopic
heart injury is associated with an immediate life-threatening condition. Troponin
levels were elevated in 43 % of the patients after admission to the hospital.
Moreover, troponin serum concentrations were significantly higher in patients
treated with norepinephrine (26.4 +/- 4 ng/l) and in non-survivors (84.9 +/- 22.8
ng/l) compared to patients without catecholamines and survivors, respectively.
CONCLUSIONS: Macroscopic heart injury was 20 times more frequent in non-survivors
than in survivors. Serum troponin levels correlated with mortality after multiple
injury and therefore may represent a valuable prognostic marker in trauma
patients.
PMID- 27501710
TI - Pancreatic Duct Holder and Mucosa Squeeze-out Technique for Duct-to-Mucosa
Pancreatojejunostomy After Pancreatoduodenectomy: Propensity Score Matching
Analysis.
AB - BACKGROUND: Duct-to-mucosa pancreatojejunostomy after pancreatoduodenectomy can
be technically difficult, particularly in cases with a non-dilated pancreatic
duct. We devised a novel procedure employing a pancreatic duct holder and mucosa
squeeze-out technique facilitating duct-to-mucosa anastomosis. We compared the
perioperative outcomes of pancreatoduodenectomy with duct-to-mucosa
pancreatojejunostomy between the novel and conventional procedures. METHODS: Our
pancreatic holder has a cone-shaped tip with a slit. The holder can expand the
pancreatic duct and provides a good surgical field for anastomosis. A small
incision for anastomosis is made on the jejunum, while the jejunum is grasped
around the incision. Then, the jejunal mucosa becomes squeezed-out and everted.
This mucosa squeeze-out technique facilitates suturing the full thickness of the
jejunum. Propensity score matching yielded 113 cases each undergoing the novel
and the conventional procedure, among 308 cases receiving pancreatoduodenectomy
with duct-to-mucosa pancreatojejunostomy. RESULTS: The overall morbidity rate was
significantly lower in the novel procedure group. The pancreatic fistula (ISGPF
grade B/C) rate was significantly lower in the novel (5 %) than in the
conventional (13 %) procedure group. For cases with a non-dilated pancreatic duct
(<=3 mm), the rate was significantly lower in the novel (10 %) than in the
conventional procedure group (24 %). Multivariate analysis identified a non
dilated pancreatic duct, soft pancreas, and the conventional procedure as factors
independently predicting the complication of pancreatic fistula formation.
CONCLUSIONS: Our novel procedure facilitates duct-to-mucosa pancreatojejunostomy
and decreases the pancreatic fistula rate. This procedure is simple, rational,
and useful for achieving anastomosis, particularly in cases with a non-dilated
pancreatic duct.
PMID- 27501711
TI - [Dermatoscopy without a dermatoscope].
PMID- 27501712
TI - [Maculonodular lesion on the back of a 66-year-old man].
PMID- 27501713
TI - Review: Therapeutic Targeting of HMGB1 in Stroke.
AB - High mobility group box-1 (HMGB1) is a nuclear protein that is expressed in
almost all eukaryotic cells. In the nucleus, it maintains nuclear homeostasis and
promotes gene transcription. HMGB1 can be passively released into the
extracellular milieu after cell necrosis or actively secreted by activated immune
cells. HMGB1 has several receptors such as Toll-like receptor 2, Toll-like
receptor 4, and the receptor for advanced glycation end products. After brain
injury, HMGB1 is released early from neural cells and contributes to the initial
stages of the inflammatory response. However, surprisingly, HMGB1 can mediate
beneficial effects during the course of stroke recovery. The biphasic biological
property of extracellular HMGB1 may be related to the redox modifications of its
cysteine residues. This review discusses the emerging roles of HMGB1 in several
stroke models, as well as its potential role as a therapeutic target for stroke
patients.
PMID- 27501714
TI - Water-soluble Complex of Curcumin with Cyclodextrins: Enhanced Physical
Properties For Ocular Drug Delivery.
AB - BACKGROUND: Curcumin, a natural hydrophobic polyphenol, has been reported to have
diverse pharmacological activities. Previous studies have evaluated its efficacy
using both oral and transdermal dosage forms. However, two major obstacles-poor
aqueous solubility and low stability-severely limited its pharmaceutical use.
OBJECTIVE: The main objective of this study was to prepare curcumin eye drops
that provided sustained release to allow for once daily application in retinitis
pigmentosa. METHOD: To achieve our goal, curcumin was complexed with beta
cyclodextrin and hydroxypropyl-beta- cyclodextrin in two molar ratios (1:1 and
1:2) using co-solvent, co-solvent with sonication and freezedrying filtration
methods. A total of 12 complexes were prepared, then characterized using
differential scanning calorimetry, powder X-ray diffraction, Fourier transform
infrared spectroscopy, scanning electron microscopy, solubility assessment and in
vitro release studies. RESULTS: An improvement in curcumin aqueous solubility
relative to pure curcumin was achieved for all 12 complexes. However, the freeze
drying filtration method was superior to all other methods because it produced
highly water-soluble drug-CD complexes. Based on our stability analyses, pH 6.8
phosphate buffer containing 1% Tween 80 was selected as the release medium for in
vitro release studies because curcumin exhibited high stability in this medium.
Our F11 formulation provided sustained release of the drug for more than 96 h
with a maximum amount released of drug (21.77+/-0.26 MUg/ml). Our in vitro
release data also showed that release of drug from curcumin-CDs inclusion
complexes followed a Higuchi non-Fickian diffusion mechanism. CONCLUSION: Based
on these results, F11 was formulated as eye drops, which provide a promising once
daily novel topical delivery of this naturally derived phytochemical.
PMID- 27501715
TI - Novel Drug Delivery System for Dermal Uptake of Etofenamate: Semisolid SLN
Dispersion.
AB - BACKGROUND: Semisolid SLNs are novel strategy for dermal drug administration
instead of incorporating the SLN dispersions into conventional semisolids.
Etofenamate loaded semisolid SLNs were successfully prepared and in vitro
characterization of formulations were performed in our previous study. The
present study is an attempt to evaluate the dermal behavior of the semisolid SLNs
selected on the basis of previous research and investigate the properties in
terms of the convenience for topical applications. OBJECTIVE: The objective of
this study is to evaluate the skin penetration characteristics of semisolid SLN
formulations. The occlusive and mechanical properties of semisolid SLNs were also
evaluated because of their impression on the dermal behavior of the formulations.
METHOD: The occlusive properties were investigated by in vitro occlusion test.
Texture analysis was performed to define the hardness, compressibility,
adhesiveness, cohesiveness and elasticity of the formulations. Rat skin was
chosen to evaluate the ex vivo penetration of etofenamate loaded semisolid SLNs
and commercial gel product. Coumarin-6 was used to visualize the dermal
distribution of the semisolid SLN formulations. For monitorizing the penetration
of coumarin-6 into the skin samples Confocal Laser Scanning Microscopy was
employed. RESULTS: The occlusive and mechanical properties of C1 coded semisolid
SLN formulation were found more favorable in comparison with P1. The cumulative
etofenamate amount in skin samples was found to be 39.88 +/- 1.50 MUg/cm2 for C1
and 30.56 +/- 2.10 MUg/cm2 for P1 coded formulations. According to CLSM images,
greater fluorescence intensities and deeper skin penetrations were obtained with
both of the semisolid SLNs in comparison to plain Carbopol gel. CONCLUSION: It
can be concluded that the semisolid SLNs are promising alternative dermal drug
delivery systems to the conventional dosage forms.
PMID- 27501716
TI - Drug Delivery From Hydrogels: A General Framework for the Release Modeling.
AB - The controlled delivery of drugs, including siRNAs, can be effectively obtained
using Hydrogel- Based Drugs Delivery Systems (HB-DDSs). Successful design of HB
DDSs requires the knowledge of the mechanisms that influence drug release. The
modeling of the physical phenomena involved could help in the development and
optimization of HB-DDS, sensibly reducing the time and costs required by a trial
and-error procedures. The modeling is rather complex because of the presence of
several, synergistic and competing, transport phenomena. In this work a general
framework useful for modeling the HB-DDS has been derived and it is proposed,
coupling and homogenizing the literature models. It is shown that all of them can
be traced back to two different approaches: multiphasic models and multicomponent
mixture models. In the first one the hydrogel is seen as constituted by different
phases, the behavior of each one being described by their own mass and momentum
conservation equations. In the second approach, the hydrogel is considered as
made of one phase composed by several components.
PMID- 27501717
TI - Current Therapeutic Drugs Against Cerebral Vasospasm after Subarachnoid
Hemorrhage: A Comprehensive Review of Basic and Clinical Studies.
AB - BACKGROUND: Cerebral vasospasm (CVS) is well known as a major complication in
subarachnoid hemorrhage (SAH) patients, and research has long been focused on
improving morbidity and mortality. As CVS commonly develops from day 4 to day 14
after SAH onset, SAH patients require therapies with drugs for preventing CVS
after surgical treatment for the source of hemorrhage, mostly ruptured
intracranial aneurysms. It is thought that the pathogenesis of CVS is initiated
by prolonged smooth muscle contraction, and the subsequent hypoperfusion and
cytotoxic responses induce cerebral ischemia. Although therapeutic investigations
have historically focused on morphological improvement, the improvement of
outcome is limited by the reversal of arterial narrowing. Therefore, it might be
important to look back at evidence from long-lasting studies of CVS and to
determine a highroad to effective drugs, including combination therapy.
OBJECTIVE: In this review, we introduce current candidate beneficial drugs
against CVS in clinical SAH, including nimodipine and other Ca2+ channel
antagonists, magnesium sulfate, clazosentan, statins, cilostazol,
eicosapentaenoic acid, fasudil hydrochloride, milrinone, and edaravone, all of
which have been frequently studied in recent years.
PMID- 27501718
TI - A draft genome of the brown alga, Cladosiphon okamuranus, S-strain: a platform
for future studies of 'mozuku' biology.
AB - The brown alga, Cladosiphon okamuranus (Okinawa mozuku), is economically one of
the most important edible seaweeds, and is cultivated for market primarily in
Okinawa, Japan. C. okamuranus constitutes a significant source of fucoidan, which
has various physiological and biological activities. To facilitate studies of
seaweed biology, we decoded the draft genome of C. okamuranus S-strain. The
genome size of C. okamuranus was estimated as ~140 Mbp, smaller than genomes of
two other brown algae, Ectocarpus siliculosus and Saccharina japonica Sequencing
with ~100* coverage yielded an assembly of 541 scaffolds with N50 = 416 kbp.
Together with transcriptomic data, we estimated that the C. okamuranus genome
contains 13,640 protein-coding genes, approximately 94% of which have been
confirmed with corresponding mRNAs. Comparisons with the E. siliculosus genome
identified a set of C. okamuranus genes that encode enzymes involved in
biosynthetic pathways for sulfated fucans and alginate biosynthesis. In addition,
we identified C. okamuranus genes for enzymes involved in phlorotannin
biosynthesis. The present decoding of the Cladosiphon okamuranus genome provides
a platform for future studies of mozuku biology.
PMID- 27501720
TI - Caregiver characteristics and bereavement needs: Findings from a population
study.
AB - BACKGROUND: Globally, most care for people with life-limiting illnesses is
provided by informal caregivers. Identifying characteristics of caregivers that
may have unmet needs and negative outcomes can help provide better support to
facilitate adjustment. AIM: We compared characteristics, expressed unmet needs
and outcomes for spousal caregivers, with other caregivers at the end of life, by
gender and age. DESIGN: The South Australian Health Omnibus is an annual, random,
face-to-face, cross-sectional survey wherein respondents are asked about end-of
life care. SETTING/PARTICIPANTS: Participants were aged over 15 years, resided in
households in South Australia and had someone close to them die from a terminal
illness in the last 5 years. RESULTS: Of the 1540 respondents who provided hands
on care for someone close at the end of life, 155 were widows/widowers. Bereaved
spousal caregivers were more likely to be older, female, better educated, have
lower incomes, less full-time work, English as second language, sought help with
grief and provided more day-to-day care for longer periods. Spousal caregivers
were less likely to be willing to take on caregiving again, less able to 'move
on' with life and needed greater emotional support and information about illness
and services. The only difference between widows and widowers was older age of
spouse in women. Younger spousal caregivers perceived greater unmet emotional
needs and were significantly less likely to be able to 'move on'. CONCLUSION:
Spousal caregivers are different from other caregivers, with more intense needs
that are not fully met. These have implications for bereavement, health and
social services.
PMID- 27501719
TI - Biomechanics and Physiology of Uphill and Downhill Running.
AB - Most running studies have considered level running (LR), yet the regulation of
locomotor behaviour during uphill (UR) and downhill (DR) running is fundamental
to increase our understanding of human locomotion. The purpose of this article
was to review the existing literature regarding biomechanical, neuromuscular and
physiological adaptations during graded running. Relative to LR, UR is
characterized by a higher step frequency, increased internal mechanical work,
shorter swing/aerial phase duration, and greater duty factor, while DR is
characterized by increased aerial time, reduced step frequency and decreased duty
factor. Grade also modifies foot strike patterns, with a progressive adoption of
a mid- to fore-foot strike pattern during UR, and rear-foot strike patterns
during DR. In UR, lower limb muscles perform a higher net mechanical work
compared to LR and DR to increase the body's potential energy. In DR, energy
dissipation is generally prevalent compared to energy generation. The increased
demands for work as running incline increases are met by an increase in power
output at all joints, particularly the hip. This implies that UR requires greater
muscular activity compared to LR and DR. Energy cost of running (C r) linearly
increases with positive slope but C r of DR decreases until a minimum slope is
reached at -20 %, after which C r increases again. The effects of slope on
biomechanics, muscle contraction patterns and physiological responses have
important implications for injury prevention and success of athletes engaged in
graded running competitions.
PMID- 27501721
TI - Is Sedentary Lifestyle Associated With Testicular Function? A Cross-Sectional
Study of 1,210 Men.
AB - Based on cross-sectional data on 1,210 healthy young Danish men, we investigated
whether sedentary lifestyle was associated with testicular function (semen
quality and reproductive hormones) independent of physical activity. The men were
invited to participate in the study between 2008 and 2012, when they attended a
compulsory medical examination to determine their fitness for military service.
Information on sedentary behavior (television watching and computer time) and
physical activity was obtained by questionnaire. The men had a physical
examination, delivered a semen sample, and had a blood sample drawn. Time spent
watching television, but not time sitting in front of a computer, was associated
with lower sperm counts. Men who watched television more than 5 hours/day had an
adjusted sperm concentration of 37 million/mL (95% confidence interval (CI): 30,
44) versus 52 million/mL (95% CI: 43, 62) among men who did not watch television;
total sperm counts in those 2 groups were 104 million (95% CI: 84, 126) and 158
million (95% CI: 130, 189), respectively. Furthermore, an increase in follicle
stimulating hormone and decreases in testosterone and the
testosterone/luteinizing hormone ratio were detected in men watching many hours
of television. Self-rated physical fitness, but not time spent on physical
activity, was positively associated with sperm counts.
PMID- 27501722
TI - Erratum to: Serum B cell-activating factor (BAFF) level in connective tissue
disease associated interstitial lung disease.
PMID- 27501723
TI - Erratum to: Conformational changes and translocation of tissue-transglutaminase
to the plasma membranes: role in cancer cell migration.
PMID- 27501724
TI - Iterative development of Vegethon: a theory-based mobile app intervention to
increase vegetable consumption.
AB - BACKGROUND: Mobile technology may serve as a cost-effective and scalable tool for
delivering behavioral nutrition interventions. This research sought to
iteratively develop a theory-driven mobile app, Vegethon, to increase vegetable
consumption. METHODS: Development of Vegethon followed phases outlined by the
IDEAS framework: 1) empathize with users (qualitative interviews, n = 18); 2)
specify target behavior; 3) ground in behavioral theory; 4) ideate implementation
strategies; 5) prototype potential products; 6) gather user feedback (qualitative
interviews, n = 14; questionnaire, n = 41); 7) build minimum viable product; and
8) pilot potential efficacy and usability (pilot RCT, n = 17). Findings from each
phase informed subsequent phases. The target population that informed
intervention development was 18-50 years of age, had BMIs of 28-40 kg/m(2), and
lived in the geographical area surrounding Stanford University. A full
description of the final version of Vegethon is included in the paper. RESULTS:
Qualitative findings that shaped initial intervention conception were:
participants' interests in accountability without judgment; their desire for
simple and efficient dietary self-monitoring; and the importance of planning
meals in advance. Qualitative findings identified during intervention refinement
were the need for a focus on vegetable self-monitoring; inclusion of vegetable
challenges; simplification of features; advice and inspiration for eating
vegetables; reminder notifications; and peer comparison. Pilot RCT findings
suggested the initial efficacy, acceptance, and feasibility of the intervention.
The final version of Vegethon enabled easy self-monitoring of vegetable
consumption and included a range of features designed to engage the user (e.g.,
surprise challenges; leaderboard; weekly reports). Vegethon was coded for its
inclusion of 18 behavior change techniques (BCTs) (e.g., goal setting; feedback;
social comparison; prompts/cues; framing/reframing; identity). CONCLUSIONS:
Vegethon is a theory-based, user-informed mobile intervention that was
systematically developed using the IDEAS framework. Vegethon targets increased
vegetable consumption among overweight adults and is currently being evaluated in
a randomized controlled efficacy trial. TRIAL REGISTRATION: Clinical Trials.gov:
NCT01826591.
PMID- 27501726
TI - The safety of laparoscopic sleeve gastrectomy among diabetic patients.
AB - AIMS: Laparoscopic sleeve gastrectomy (LSG) is a commonly performed bariatric
procedure. Although bariatric surgery is becoming increasingly recognized as a
treatment option for diabetes, there remain concerns about the operative risks
faced by diabetic patients. This study's objective was to determine the safety of
bariatric surgery in diabetic patients, specifically the type 2 diabetic (T2DM)
population. METHODS: Patients over 18 years of age with a body mass index (BMI)
>= 35 kg/m2 who underwent LSG in 2012 in the ACS-NSQIP database were identified.
Emergency cases were excluded from analysis. Data included patient demographics,
comorbidities, length of stay, and 30-day complications. The primary outcome was
30-day overall complication rate, and secondary outcomes included major
complications and reoperation rates. RESULTS: There were 6399 LSG in the NSQIP
database in 2012. Three hundred and twenty-two patients were excluded for BMI <
35, and 15 cases were deemed emergencies and excluded. Of the 6062 LSG who met
the study criteria, 4726 (78 %) of patients were non-diabetic, 941 (15.5 %) had
T2DM, and 395 (6.5 %) had T1DM. T2DM patients were more likely to be male (28.9
vs. 19.3 %, p < 0.001), were older (47.6 years vs. 42.5 years, p < 0.001), and
had a higher BMI (46.4 vs. 45.7 kg/m2, p = 0.027) compared with non-diabetics.
The overall 30-day complication rate did not differ between groups (6.5 % T2DM
vs. 5.6 % non-diabetic, p = 0.292). After controlling for possible confounders,
T2DM remained at no increased risk of 30-day complications (OR 1.16, 95 % CI 0.87
1.55, p = 0.301). In sub-analyses of specific complications, T2DM had a slightly
higher rate of blood transfusions (1.8 vs. 1.0 %, p = 0.037). Other postoperative
complications did not differ between groups. The 30-day complication rate for
type 1 diabetics was greater than for T2DM (9.9 vs. 6.5 %, p = 0.031) and non
diabetics (9.9 vs. 5.6 %, p < 0.001). CONCLUSION: Laparoscopic sleeve gastrectomy
is a safe procedure for type 2 diabetics with regard to early postoperative
complications.
PMID- 27501727
TI - A hands-free region-of-interest selection interface for solo surgery with a wide
angle endoscope: preclinical proof of concept.
AB - BACKGROUND: A hands-free region-of-interest (ROI) selection interface is proposed
for solo surgery using a wide-angle endoscope. A wide-angle endoscope provides
images with a larger field of view than a conventional endoscope. With an
appropriate selection interface for a ROI, surgeons can also obtain a detailed
local view as if they moved a conventional endoscope in a specific position and
direction. METHODS: To manipulate the endoscope without releasing the surgical
instrument in hand, a mini-camera is attached to the instrument, and the images
taken by the attached camera are analyzed. When a surgeon moves the instrument,
the instrument orientation is calculated by an image processing. Surgeons can
select the ROI with this instrument movement after switching from 'task mode' to
'selection mode.' The accelerated KAZE algorithm is used to track the features of
the camera images once the instrument is moved. Both the wide-angle and detailed
local views are displayed simultaneously, and a surgeon can move the local view
area by moving the mini-camera attached to the surgical instrument. RESULTS:
Local view selection for a solo surgery was performed without releasing the
instrument. The accuracy of camera pose estimation was not significantly
different between camera resolutions, but it was significantly different between
background camera images with different numbers of features (P < 0.01). The
success rate of ROI selection diminished as the number of separated regions
increased. However, separated regions up to 12 with a region size of 160 * 160
pixels were selected with no failure. Surgical tasks on a phantom model and a
cadaver were attempted to verify the feasibility in a clinical environment.
CONCLUSIONS: Hands-free endoscope manipulation without releasing the instruments
in hand was achieved. The proposed method requires only a small, low-cost camera
and an image processing. The technique enables surgeons to perform solo surgeries
without a camera assistant.
PMID- 27501728
TI - A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based
on real-time analysis of the mucosal lipidome: a prospective observational study
of the iKnife.
AB - BACKGROUND: This pilot study assessed the diagnostic accuracy of rapid
evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and
colonic adenomas. METHODS: Patients undergoing elective surgical resection for
CRC were recruited at St. Mary's Hospital London and The Royal Marsden Hospital,
UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with
aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass
spectrometer (Waters Corporation). Histological examination was performed for
validation purposes. Multivariate analysis was performed using principal
component analysis and linear discriminant analysis in Matlab 2015a (Mathworks,
Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used
prospectively in five patients to assess its feasibility during hot snare
polypectomy. RESULTS: Twenty-eight patients were recruited (12 males, median age
71, range 35-89). REIMS was able to reliably distinguish between cancer and
normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99).
It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma
and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus
cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial
phosphatidylglycerols were over-expressed on cancer samples, while NAM was
defined by raised plasmalogens and triacylglycerols expression and adenomas
demonstrated an over-expression of ceramides. REIMS was able to classify samples
according to tumor differentiation, tumor budding, lymphovascular invasion,
extramural vascular invasion and lymph node micrometastases (AUC's 0.88, 0.87,
0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic
REIMS was able to detect target lipid species such as ceramides during hot snare
polypectomy. CONCLUSION: REIMS demonstrates high diagnostic accuracy for tumor
type and for established histological features of poor prognostic outcome in CRC
based on a multivariate analysis of the mucosal lipidome. REIMS could augment
endoscopic and imaging technologies for precision phenotyping of colorectal
cancer.
PMID- 27501725
TI - Telomeres and telomerase in head and neck squamous cell carcinoma: from
pathogenesis to clinical implications.
AB - Strongly associated with tobacco use, heavy alcohol consumption, and with high
risk human papillomavirus (HPV) infection, head and neck squamous cell carcinoma
(HNSCC) is a frequently lethal, heterogeneous disease whose pathogenesis is a
multistep and multifactorial process involving genetic and epigenetic events. The
majority of HNSCC patients present with locoregional advanced stage disease and
are treated with combined modality strategies that can markedly impair quality of
life and elicit unpredictable results. A large fraction of those who undergo
locoregional treatment and achieve a complete response later develop locoregional
recurrences or second field tumors. Biomarkers that are thus able to stratify
risk and enable clinicians to tailor treatment plans and to personalize post
therapeutic surveillance strategies are highly desirable. To date, only HPV
status is considered a reliable independent predictor of treatment response and
survival in patients with HNSCC arising from the oropharyngeal site. Recent
studies suggest that telomere attrition, which may be an early event in human
carcinogenesis, and telomerase activation, which is detected in up to 90 % of
malignancies, could be potential markers of cancer risk and disease outcome. This
review examines the current state of knowledge on and discusses the implications
linked to telomere dysfunction and telomerase activation in the development and
clinical outcome of HNSCC.
PMID- 27501730
TI - Endoscopic control of enterocutaneous fistula by dual intussuscepting stent
technique.
AB - INTRODUCTION: Large high-output enterocutaneous fistulas pose great difficulties,
especially in the setting of recent surgery and compromised skin integrity.
METHODS: This video demonstrates a new technique of endoscopic control of
enterocutaneous fistula by using two covered overlapping stents. In brief, the
two stents are each inserted endoscopically, one proximal, and the other distal
to the fistula with 2 cm of each stent protruding cutaneously. Following this,
the proximal stent is crimped and intussuscepted into the distal stent with an
adequate overlap. A prolene suture is passed through the anterior wall of both
stents to prevent migration. The two stents used were evolution esophageal stents
10 cm long, fully covered, double-flared with non-flared and flared diameters
being 20 and 25 mm, respectively (product number EVO-FC-20-25-10-E, Cook Medical,
Bloomington, IN, USA). RESULTS: The patient featured in this video developed a
high-output enterocutaneous fistula proximal to a loop ileostomy, which was
created following a small bowel leak after a curative surgery for bladder cancer.
Using the technique featured in this video (schematic depicted in Fig. 1), the
patient was nutritionally optimized with oral feeds from albumin of 0.9-3.4 g/dl
within 2 months despite prior failure to achieve nutrition optimization and
adequate skin protection with combination of oral and/or parenteral nutrition.
Three months after stenting, following nutritional optimization and improvement
of skin coverage, definitive procedure consisted of uncomplicated fistula
resection with primary stapled side-to-side functional end-to-end anastomosis.
The stents were not completely incorporated into the mucosa and were rather
easily pulled through the residual fistula opening just prior to the surgery.
Only minimal fibrosis was noted and less than 20 cm of involved small bowel
needed to be resected. Had the fistula have closed completely, the options would
have included (1) proceeding to bowel resection with removal of the stents
regardless of closure, or (2) cutting the securing prolene stitch and
observation. Considering the placement of the stents in mid-small bowel, their
endoscopic retrieval would have been difficult unless they were to migrate into
the colon. CONCLUSIONS: Although a prior attempt at managing an enterocutaneous
fistula with a stent deployed through a colostomy site was previously reported
[1], there is no published account of bridging an enterocutaneous fistula with
overlapping endoscopic stents through the fistula itself. This video serves as a
proof of concept for temporizing enterocutaneous fistulas with endoscopic
stenting.
PMID- 27501729
TI - Mucosal perforation during laparoscopic surgery for achalasia: impact of
preoperative pneumatic balloon dilation.
AB - BACKGROUND: Controversy remains whether preoperative pneumatic balloon dilation
(PBD) influences the surgical outcome of laparoscopic esophagocardiomyotomy in
patients with esophageal achalasia. The aim of this study was to evaluate whether
preoperative PBD represents a risk factor for surgical complications and affects
the symptomatic and/or functional outcomes of laparoscopic Heller myotomy with
Dor fundoplication (LHD). METHODS: A retrospective chart review was conducted on
a prospectively compiled surgical database of 103 consecutive patients with
esophageal achalasia who underwent LHD from November 1994 to September 2014. The
following data were compared between the patients with preoperative PBD (PBD
group; n = 26) and without PBD (non-PBD group; n = 77): (1) patients'
demographics: age, gender, body mass index, duration of symptoms, maximum
transverse diameter of esophagus; (2) operative findings: operating time, blood
loss, intraoperative complications; (3) postoperative course: complications,
clinical symptoms, postoperative treatment; and (4) esophageal functional tests:
preoperative and postoperative manometric data and postoperative profile of 24-h
esophageal pH monitoring. RESULTS: (1) No significant differences were observed
in the patients' demographics. (2) Operative findings were similar between the
two groups; however, the incidence of mucosal perforation was significantly
higher in the PBD group (n = 8; 30.7 %) compared to the non-PBD group (n = 6; 7.7
%) (p = 0.005). (3) Postoperative complications were not encountered in either
group. The differences were not significant for postoperative clinical symptoms,
the incidence of gastroesophageal reflux disease, or necessity of postoperative
treatments. (4) Lower esophageal sphincter pressure was effectively reduced in
both groups, and no differences were observed in manometric data or 24-h pH
monitoring profiles between the two groups. Multivariate logistic regression
analysis showed that preoperative PBD and the maximum transverse diameter of
esophagus were significantly associated with intraoperative mucosal perforation.
CONCLUSIONS: Although postoperative outcomes were not affected, additional
caution is recommended in identifying intraoperative mucosal perforation in
patients with preoperative PBD when performing LHD.
PMID- 27501731
TI - Drawing sounds: representing tones and chords spatially.
AB - Research on the crossmodal correspondences has revealed that seemingly unrelated
perceptual information can be matched across the senses in a manner that is
consistent across individuals. An interesting extension of this line of research
is to study how sensory information biases action. In the present study, we
investigated whether different sounds (i.e. tones and piano chords) would bias
participants' hand movements in a free movement task. Right-handed participants
were instructed to move a computer mouse in order to represent three tones and
two chords. They also had to rate each sound in terms of three visual analogue
scales (slow-fast, unpleasant-pleasant, and weak-strong). The results demonstrate
that tones and chords influence hand movements, with higher-(lower-)pitched
sounds giving rise to a significant bias towards upper (lower) locations in
space. These results are discussed in terms of the literature on forward models,
embodied cognition, crossmodal correspondences, and mental imagery. Potential
applications sports and rehabilitation are discussed briefly.
PMID- 27501732
TI - Vibrotactile cuing revisited to reveal a possible challenge to sensorimotor
adaptation.
AB - Motor responses to unexpected external perturbations require the adjustment of
the motor commands driving the ongoing activity. Strategies can be learned with
practice to compensate for these unpredictable perturbations (e.g., externally
induced slips and trips). It has been hypothesized that response improvements
reflect the adaptation of motor commands through updates of an internal model.
This hypothesis may be nuanced when a pre-existing motor response could be used.
In that case, since a relatively adequate response is known, only the timing of
the command needs to be determined. If so, then it could be inferred that the
timing of movement initiation and the specific sequence of motor commands can be
dissociated. Previously, we quantified the benefits of cuing vs. learning on
recovery motor responses resulting from a trip induced by the abrupt stop of one
side of a split belt treadmill. Trip occurrence was randomized within a series of
strides. Two groups of young adults participated to two distinct experiments
(learning, cuing). In the learning experiment, trip recovery improved
progressively from the 4th to the 8th trial to reach an "adapted response". In
the cuing experiment, trip recovery was immediate (from 1st trial). Expanding
from these results, the aim of the present work was to differentiate the
processes underlying the generation of motor compensation strategies in response
to an external perturbation under time uncertainty. A supplementary analysis
revealed that "cued" responses were kinematically similar to the "adapted
response" and remained invariant regardless of cue lead time (250, 500 ms before
trip) and application location of the cue (arm, trunk, lower leg). It is posited
that all responses (cued and non-cued) are the expression of a pre-existing motor
program derived from life experiences. Here, the cue significantly reduces time
uncertainty and adaptation consists primarily in resolving time uncertainty based
on the trial-by-trial learning of the stochastic property of trip occurrence in
order to reduce the response delay. Hence, response time delay and motor program
parameters appear to stem from two distinct processes.
PMID- 27501733
TI - Adolescents', mothers', and fathers' reports of adherence across adolescence and
their relation to HbA1c and daily blood glucose.
AB - This study examined what is measured by adolescents', mothers', and fathers'
reports of adolescents' adherence to the type 1 diabetes regimen and how such
reports relate to HbA1c and daily blood glucose. Two-hundred fifty-two
adolescents (M age = 12.49 at baseline), mothers, and 188 fathers completed an
adapted Self-Care Inventory (LaGreca et al. in Child Health Care 19(3):132-139,
1990) every 6 months for 2.5 years, HbA1c was gathered from medical records, and
daily number of blood glucose tests (BGT) and blood glucose mean (BGM) were
obtained from glucose meters at one time point. A multitrait-multimethod approach
decomposing adherence indicated that fathers' reports reflected a stable
perception across time, mothers' reports a shared view within the family that
varied with HbA1c across time, and adolescents' reports a unique view. Fathers'
and mothers' reports were related to HbA1c; adolescents' reports were not, but
were uniquely associated with BGT. Family members' adherence reports capture
different information across time, with implications for measuring adherence and
for family processes.
PMID- 27501734
TI - Fatalism and hypertension prevalence, awareness, treatment and control in US
Hispanics/Latinos: results from HCHS/SOL Sociocultural Ancillary Study.
AB - Compared with non-Hispanic whites, US Hispanics/Latinos display similar
hypertension prevalence, but lower awareness, treatment, and control.
Sociocultural factors may affect these patterns. Fatalism, the belief that health
is predetermined by fate, relates to poorer adoption of risk reducing health
behaviors. We examined the association of fatalism with hypertension prevalence,
awareness, treatment, and control among 5313 Hispanics/Latinos, ages 18-74, who
were enrolled from four US communities in the Hispanic Community Health
Study/Study of Latinos Sociocultural Ancillary Study. After accounting for
socioeconomic status and acculturation in logistic regression analyses, higher
fatalism was associated with increased odds of hypertension (OR 1.14, 95 % CI
1.02, 1.28). This association was non-significant when diabetes and other health
related covariates were statistically adjusted. Fatalism was not associated with
hypertension awareness, treatment, or control. Findings suggest that the
association of fatalism with hypertension may be due largely to its association
with SES, acculturation, or related health conditions.
PMID- 27501735
TI - Towards valid 'serious non-fatal injury' indicators for international comparisons
based on probability of admission estimates.
AB - BACKGROUND: Governments wish to compare their performance in preventing serious
injury. International comparisons based on hospital inpatient records are
typically contaminated by variations in health services utilisation. To reduce
these effects, a serious injury case definition has been proposed based on
diagnoses with a high probability of inpatient admission (PrA). The aim of this
paper was to identify diagnoses with estimated high PrA for selected developed
countries. METHODS: The study population was injured persons of all ages who
attended emergency department (ED) for their injury in regions of Canada,
Denmark, Greece, Spain and the USA. International Classification of Diseases
(ICD)-9 or ICD-10 4-digit/character injury diagnosis-specific ED attendance and
inpatient admission counts were provided, based on a common protocol. Diagnosis
specific and region-specific PrAs with 95% CIs were calculated. RESULTS: The
results confirmed that femoral fractures have high PrA across all countries
studied. Strong evidence for high PrA also exists for fracture of base of skull
with cerebral laceration and contusion; intracranial haemorrhage; open fracture
of radius, ulna, tibia and fibula; pneumohaemothorax and injury to the liver and
spleen. Slightly weaker evidence exists for cerebellar or brain stem laceration;
closed fracture of the tibia and fibula; open and closed fracture of the ankle;
haemothorax and injury to the heart and lung. CONCLUSIONS: Using a large study
size, we identified injury diagnoses with high estimated PrAs. These diagnoses
can be used as the basis for more valid international comparisons of life
threatening injury, based on hospital discharge data, for countries with well
developed healthcare and data collection systems.
PMID- 27501736
TI - Protective effect of porcine placenta in a menopausal ovariectomized mouse.
PMID- 27501737
TI - Nocturnal hypoxia in obese-related obstructive sleep apnea as a putative trigger
of oxidative stress in pediatric NAFLD progression.
PMID- 27501739
TI - Propolis: a potential natural product to fight Candida species infections.
AB - AIM: To evaluate the effect of propolis against Candida species planktonic cells
and its counterpart's biofilms. MATERIALS & METHODS: The MIC values, time-kill
curves and filamentation form inhibition were determined in Candida planktonic
cells. The effect of propolis on Candida biofilms was assessed through
quantification of CFUs. RESULTS: MIC values, ranging from 220 to 880 ug/ml,
demonstrated higher efficiency on C. albicans and C. parapsilosis than on C.
tropicalis cells. In addition, propolis was able to prevent Candida species
biofilm's formation and eradicate their mature biofilms, coupled with a
significant reduction on C. tropicalis and C. albicans filamentation. CONCLUSION:
Propolis is an inhibitor of Candida virulence factors and represents an
innovative alternative to fight candidiasis.
PMID- 27501740
TI - Retracted: Aetiology and clinical profile of children with 46, XY differences of
sex development at an Indian referral centre.
AB - Retraction: 'Aetiology and clinical profile of children with 46, XY differences
of sex development at an Indian referral centre' by Vasundhera Chauhan, Rima
Dada, Vandana Jain The above article, published online on 8 August 2016 in Wiley
Online Library (http://wileyonlinelibrary.com), has been retracted by agreement
between the authors, the Journal Editors-in-Chief, Wolf-Bernhard Schill and Ralf
Henkel, and Blackwell Verlag GmbH. The retraction has been agreed as the result
of an unresolved dispute between the first author and a colleague research fellow
due to the inclusion of data from patients who were simultaneously enrolled in
two studies being conducted separately by the two parties. Reference Chauhan, V.,
Dada, R. and Jain, V. (2016), Aetiology and clinical profile of children with 46,
XY differences of sex development at an Indian referral centre. Andrologia.
doi:10.1111/and.12663.
PMID- 27501738
TI - Nocturnal hypoxia-induced oxidative stress promotes progression of pediatric non
alcoholic fatty liver disease.
AB - BACKGROUND & AIMS: Oxidative stress is proposed as a central mediator in NAFLD
pathogenesis, but the specific trigger for reactive oxygen species generation has
not been clearly delineated. In addition, emerging evidence shows that obesity
related obstructive sleep apnea (OSA) and nocturnal hypoxia are associated with
NAFLD progression in adults. The aim of this study was to determine if
OSA/nocturnal hypoxia-induced oxidative stress promotes the progression of
pediatric NAFLD. METHODS: Subjects with biopsy proven NAFLD and lean controls
were studied. Subjects underwent polysomnograms, liver histology scoring,
laboratory testing, urine F(2)-isoprostanes (measure of lipid peroxidation) and 4
hydroxynonenal liver immunohistochemistry (in situ hepatic lipid peroxidation).
RESULTS: We studied 36 adolescents with NAFLD and 14 lean controls. The
OSA/hypoxia group (69% of NAFLD subjects) had more severe fibrosis (64% stage 0
2; 36% stage 3) than those without OSA/hypoxia (100% stage 0-2), p=0.03. Higher
F(2)-isoprostanes correlated with apnea/hypoxia index (r=0.39, p=0.03), % time
SaO2 <90% (r=0.56, p=0.0008) and inversely with SaO2 nadir (r=-0.46, p=0.008).
OSA/hypoxia was most severe in subjects with the greatest 4HNE staining (p=0.03).
Increasing F(2)-isoprostanes(r=0.32, p=0.04) and 4HNE hepatic staining (r=0.47,
p=0.007) were associated with worsening steatosis. Greater oxidative stress
occurred in subjects with definite NASH as measured by F(2)-isoprostanes (p=0.06)
and hepatic 4HNE (p=0.03) compared to those with borderline/not NASH.
CONCLUSIONS: These data support the role of nocturnal hypoxia as a trigger for
localized hepatic oxidative stress, an important factor associated with the
progression of NASH and hepatic fibrosis in obese pediatric patients. LAY
SUMMARY: Obstructive sleep apnea and low nighttime oxygen are associated with
NAFLD progression in adults. In this study, we show that adolescents with NAFLD
who have OSA and low oxygen have significant scar tissue in their livers. NAFLD
subjects affected by OSA and low oxygen have a greater imbalance between the
production of free radicals and their body's ability to counteract their harmful
effects than subjects without OSA and low oxygen. This study shows that low
oxygen levels may be an important trigger in the progression of pediatric NASH.
PMID- 27501741
TI - Hollow silica nanospheres coated with insoluble calcium salts for pH-responsive
sustained release of anticancer drugs.
AB - Hollow silica nanospheres coated with biocompatible and pH-sensitive inorganic
insoluble calcium salts including calcium carbonate and hydroxyapatite have been
successfully prepared. The results indicate that the nanospheres can efficiently
load doxorubicin and release it in a pH-responsive and sustained manner, and
improve the treatment efficacy significantly.
PMID- 27501742
TI - Cu(i)-Catalyzed oxidative homo-coupling of thiazoline-4-carboxylates: synthesis
of 4,4'-bithiazoline derivatives.
AB - Cu(i)-Catalyzed oxidative homo-coupling of thiazoline-4-carboxylates with good
functional group tolerance has been developed. The methodology presented an
efficient method to directly construct vicinal carbon-hetero quaternary centers
existing in numerous functional molecules and could be applied to the synthesis
of 4,4'-bithiazoles which are difficult to prepare by direct C-H activation.
PMID- 27501743
TI - Aging Reduces an ERRalpha-Directed Mitochondrial Glutaminase Expression
Suppressing Glutamine Anaplerosis and Osteogenic Differentiation of Mesenchymal
Stem Cells.
AB - Aging deteriorates osteogenic capacity of mesenchymal stem/stromal cells (MSCs),
contributing to imbalanced bone remodeling and osteoporosis. Glutaminase (Gls)
catabolizes glutamine into glutamate at the first step of mitochondrial glutamine
(Gln)-dependent anaplerosis which is essential for MSCs upon osteogenic
differentiation. Estrogen-related receptor alpha (ERRalpha) regulates genes
required for mitochondrial function. Here, we found that ERRalpha and Gls are
upregulated by osteogenic induction in human MSCs (hMSCs). In contrast,
osteogenic differentiation capacity and glutamine consumption of MSCs, as well as
ERRalpha, Gls and osteogenic marker genes are significantly reduced with age. We
demonstrated that ERRalpha binds to response elements on Gls promoter and affects
glutamine anaplerosis through transcriptional induction of Gls. Conversely, mTOR
inhibitor rapamycin, ERRalpha inverse agonist compound 29 or Gls inhibitor BPTES
leads to reduced Gln anaplerosis and deteriorated osteogenic differentiation of
hMSCs. Importantly, overexpression of ERRalpha or Gls restored impairment by
these inhibitors. Finally, we proved that compensated ERRalpha or Gls expression
indeed potentiated Gln anaplerosis and osteogenic capability of elderly mice MSCs
in vitro. Together, we establish that Gls is a novel ERRalpha target gene and
ERRalpha/Gls signaling pathway plays an important role in osteogenic
differentiation of MSCs, providing new sights into novel regenerative
therapeutics development. Our findings suggest that restoring age-related
mitochondrial Gln-dependent anaplerosis may be beneficial for degenerative bone
disorders such as osteoporosis. Stem Cells 2017;35:411-424.
PMID- 27501745
TI - New details of the neural architecture of the salmonid adipose fin.
AB - The adipose fin of salmonids, once widely regarded as vestigial and lacking in
function, was shown to be important to swimming efficiency in juvenile brown
trout Salmo trutta. Examination with confocal microscopy of adipose fins of S.
trutta stained with various antibodies targeting the nervous system revealed
several large nerves entering the fin and anastomosing throughout its length. The
branching nerves form a plexus with specific patterns of fine terminal branches
in the leading and trailing edges. A network of astrocyte-like cells (ALCs) that
is linked through cell processes to nerves and structural collagen reacted
positively with antibodies to glial cells. No other fish fins, including other
adipose fins, have been shown to exhibit this type of neural architecture. Many
vertebrate mechanoreceptors rely on collagen deformation to stimulate responses
in afferent nerves; similarly, the adipose fin also may function as a
mechanosensor, where passive mechanical deflection by water currents stimulates
afferent nerves.
PMID- 27501746
TI - A network meta-analysis of the relative efficacy of treatments for actinic
keratosis of the face or scalp in Europe: response to comments from Prof
Dirschka.
PMID- 27501744
TI - Microbial transformation of contraceptive drug etonogestrel into new metabolites
with Cunninghamella blakesleeana and Cunninghamella echinulata.
AB - Biotransformation of a steroidal contraceptive drug, etonogestrel (1), (13-ethyl
17beta-hydroxy-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one) was
investigated with Cunninghamella blakesleeana and C. echinulata. Five metabolites
2-6 were obtained on incubation of 1 with Cunninghamella blakesleeana, and three
metabolites, 2, 4, and 6 were isolated from the transformation of 1 with C.
echinulata. Among them, metabolites 2-4 were identified as new compounds. Their
structures were deduced as 6beta-hydroxy-11,22-epoxy-etonogestrel (2), 11,22
epoxy-etonogestrel (3), 10beta-hydroxy-etonogestrel (4), 6beta-hydroxy
etonogestrel (5), and 14alpha-hydroxy-etonogestrel (6). Compounds 1-6 were
evaluated for various biological activities. Interestingly, compound 5 was found
to be active against beta-glucuronidase enzyme with IC50 value of 13.97+/
0.12MUM, in comparison to standard compound, d-saccharic acid 1,4-lactone
(IC50=45.75+/-2.16MUM). Intestinal bacteria produce beta-glucuronidase. Increased
activity of beta-glucuronidase is responsible for the hydrolyses of glucuronic
acid conjugates of estrogen and other toxic substances in the colon, which plays
a key role in the etiology of colon cancer. Inhibition of beta-glucoronidase
enzyme therefore has a therapeutic significance. Compounds 1-6 were also found to
be non cytotoxic against 3T3 mouse fibroblast cell lines.
PMID- 27501747
TI - Reply to Letter to the Editor regarding "Management of the exposed total knee
prosthesis, a six-year review".
PMID- 27501748
TI - Self-propelled swimming simulations of bio-inspired smart structures.
AB - This paper presents self-propelled swimming simulations of a foldable structure,
whose folded configuration is a box. For self-locomotion through water the
structure unfolds and undulates. To guide the design of the structure and
understand how it should undulate to achieve either highest speed or maximize
efficiency during locomotion, several kinematic parameters were systematically
varied in the simulations: the wave type (standing wave versus traveling wave),
the smoothness of undulations (smooth undulations versus undulations of rigid
links), the mode of undulations (carangiform: mackerel-like versus anguilliform:
eel-like undulations), and the maximum amplitude of undulations. We show that the
swimmers with standing wave are slow and inefficient because they are not able to
produce thrust using the added-mass mechanism. Among the tested types of
undulation at low Reynolds number (Re) regime of [Formula: see text] (Strouhal
number of about 1.0), structures that employ carangiform undulations can swim
faster, whereas anguilliform swimmers are more economic, i.e., using less power
they can swim a longer distance. Another finding of our simulations is that
structures which are made of rigid links are typically less efficient (lower
propulsive and power efficiencies and also lower swimming speed) compared with
smoothly undulating ones because a higher added-mass force is generated by smooth
undulations. The wake of all the swimmers bifurcated at the low Re regime because
of the higher lateral relative to the axial velocity (high Strouhal number) that
advects the vortices laterally creating a double row of vortices in the wake. In
addition, we show that the wake cannot be used to predict the performance of the
swimmers because the net force in each cycle is zero for self-propelled bodies
and the pressure term is not negligible compared to the other terms.
PMID- 27501749
TI - Nanolithography using Bessel Beams of Extreme Ultraviolet Wavelength.
AB - Bessel beams are nondiffracting light beams with large depth-of-focus and self
healing properties, making them suitable as a serial beam writing tool over
surfaces with arbitrary topography. This property breaks the inherent resolution
vs. depth-of-focus tradeoff of photolithography. One approach for their formation
is to use circularly symmetric diffraction gratings. Such a ring grating was
designed and fabricated for the extreme ultraviolet (EUV) wavelength of 13.5 nm,
a candidate wavelength for future industrial lithography. Exposure of the aerial
images showed that a Bessel beam with an approximately 1 mm long z-invariant
central core of 223 nm diameter had been achieved, in good agreement with theory.
Arbitrary patterns were written using the Bessel spot, demonstrating possible
future application of Bessel beams for serial beam writing. Lithographic marks of
~30 nm size were also observed using a high resolution Bessel beam.
PMID- 27501750
TI - Themed Issue on "Metallodrugs: Activation, Targeting, and Delivery".
PMID- 27501751
TI - Crystal structure of EstSRT1, a family VIII carboxylesterase displaying
hydrolytic activity toward oxyimino cephalosporins.
AB - EstSRT1 is a family VIII carboxylesterase that hydrolyzes oxyimino third- and
fourth-generation cephalosporins, first-generation cephalosporins and ester
substrates. According to the crystal structure of EstSRT1 (2.0-A resolution),
this protein contains a large alpha/beta domain and a small alpha-helical domain
and harbors three catalytic residues (Ser71, Lys74, and Tyr160) in the cavity at
the domain interface, similarly to other family VIII carboxylesterases.
Comparison of the structures of EstSRT1 and EstU1, a family VIII carboxylesterase
with no hydrolytic activity toward bulky oxyimino cephalosporins, revealed that
EstSRT1 has a smaller active site, despite its extended substrate range. The B
factors of the active site segments that could potentially contact with the
oxyimino groups and the R2 side chains of oxyimino cephalosporins are higher in
EstSRT1 than in EstU1, thus suggesting the role of the active site's structural
flexibility in the extension of EstSRT1's substrate spectrum.
PMID- 27501752
TI - BAT3 negatively regulates lipopolysaccharide-induced NF-kappaB signaling through
TRAF6.
AB - TNF receptor-associated factor 6 (TRAF6) plays a critical role in NF-kappaB and
mitogen-activated protein kinase (MAPK) signaling pathways, both of which mediate
macrophage activation in response to pathogen-associated molecular patterns such
as bacterial endotoxin, lipopolysaccharides (LPS). In this study, we investigated
whether HLA-B associated transcript-3 (BAT3) regulates LPS-induced macrophage
activation. BAT3 physically interacted with TRAF6 in macrophages, and this
interaction was enhanced in the cells after LPS treatment. Furthermore, BAT3
inhibited the homo-oligomerization of TRAF6 as well as the interaction between
TRAF6 and its downstream kinase transforming growth factor beta-activated kinase
1 (TAK1), thereby suppressing TRAF6-mediated signaling events. Intriguingly,
TRAF6 mediated ubiquitination of BAT3 and this ubiquitination was crucial for its
inhibitory effect on TRAF6-mediated signaling. Depletion of BAT3 by RNA
interference resulted in enhancement of LPS-induced activation of the NF-kappaB
signaling with increasing expression levels of pro-inflammatory cytokines. These
findings suggest that BAT3 functions as the negative regulator of LPS-induced
macrophage activation.
PMID- 27501753
TI - Ablation of aldehyde reductase aggravates carbon tetrachloride-induced acute
hepatic injury involving oxidative stress and endoplasmic reticulum stress.
AB - Aldehyde reductase (Akr1a) has been reported to be involved in the biosynthesis
of ascorbic acid (AsA) in the mouse liver. Because Akr1a is expressed at high
levels in the liver, we aimed to investigate the role of Akr1a in liver
homeostasis by employing a carbon tetrachloride (CCl4)-induced hepatotoxicity
model. Akr1a-deficient (Akr1a(-/-)) and wild-type (WT) mice were injected
intraperitoneally with CCl4 and the extent of hepatic injury in the acute phase
was assessed. Liver damage was heavier in the Akr1a(-/-) mice than in the WT
mice. Furthermore, severe hepatic steatosis was observed in the livers of Akr1a(
/-) mice compared to WT mice and was restored to the levels in WT mice by AsA
supplementation. Since the presence or absence of AsA had no effect on the
decrease in CYP2E1 activity after the CCl4 treatment, it appears that AsA plays a
role in the process after the bioactivation of CCl4. Biomarkers for oxidative
stress and ER stress were markedly increased in the livers of Akr1a(-/-) mice and
were effectively suppressed by AsA supplementation. Based on these collective
results, we conclude that Akr1a exerts a protective effect against CCl4-induced
hepatic steatosis by replenishing AsA via its antioxidative properties.
PMID- 27501754
TI - Chronic reactive oxygen species exposure inhibits glucose uptake and causes
insulin resistance in C2C12 myotubes.
AB - Reactive oxygen species (ROS) is an important regulator in cellular signaling
transduction, and many previous studies have indicated that acute ROS stimulation
improves insulin sensitivity in skeletal muscle. In the study, we found that
chronic ROS treatment caused serious insulin resistance in C2C12 myotubes.
Glucose uptake and consumption assay indicated that pretreatment with 80 MUM H2O2
for 2 h inhibited insulin-stimulated glucose uptake in C2C12 myotubes, and the
reason for it, is that chronic H2O2 treatment decreased insulin-induced glucose
transporter 4 (GLUT4) translocation from cell plasma to cell membrane. Moreover,
Akt2 phosphorylation depended on insulin was reduced in C2C12 myotubes of chronic
H2O2 treatment. Together, this study provides further demonstration that chronic
ROS stress is associated with insulin resistance of skeletal muscle in the
progression of type 2 diabetes.
PMID- 27501755
TI - A novel role for the nuclear localization signal in regulating hnRNP K protein
stability in vivo.
AB - hnRNP K is a highly conserved nucleocytoplasmic shuttling protein, which
associates with RNAs through synergistic binding via its three KH domains. hnRNP
K is required for proper nuclear export and translational control of its mRNA
targets, and these processes are controlled by hnRNP K's movement between
subcellular compartments. Whereas the nuclear export and localization of hnRNP K
that is associated with mRNP complexes has been well studied, the trafficking of
hnRNP K that is unbound to mRNA has yet to be elucidated. To that end, we
expressed an EGFP-tagged RNA binding-defective form of hnRNP K in intact Xenopus
embryos, and found it was rapidly degraded in vivo. Deleting hnRNP K's nuclear
localization signal (NLS), which contains two prospective ubiquitination sites,
rescued the protein from degradation. These data demonstrate a novel activity for
the NLS of hnRNP K in regulating the protein's stability in vivo when it is
unbound to nucleic acids.
PMID- 27501756
TI - Long noncoding RNA XIST acts as an oncogene in non-small cell lung cancer by
epigenetically repressing KLF2 expression.
AB - Recently, long noncoding RNAs (lncRNAs) have been identified as critical
regulators in numerous types of cancers, including non-small cell lung cancer
(NSCLC). X inactivate-specific transcript (XIST) has been found to be up
regulated and acts as an oncogene in gastric cancer and hepatocellular carcinoma,
but little is known about its expression pattern, biological function and
underlying mechanism in NSCLC. Here, we identified XIST as an oncogenic lncRNA by
driving tumorigenesis in NSCLC. We found that XIST is over-expressed in NSCLC,
and its increased level is associated with shorter survival and poorer prognosis.
Knockdown of XIST impaired NSCLC cells proliferation, migration and invasion in
vitro, and repressed the tumorigenicity of NSCLC cells in vivo. Mechanistically,
RNA immune-precipitation (RIP) and RNA pull-down experiment demonstrated that
XIST could simultaneously interact with EZH2 to suppress transcription of its
potential target KLF2. Additionally, rescue experiments revealed that XIST's
oncogenic functions were partly depending on silencing KLF2 expression.
Collectively, our findings expound how XIST over-expression endows an oncogenic
function in NSCLC.
PMID- 27501757
TI - Downregulation of miR-17-92a cluster promotes autophagy induction in response to
celastrol treatment in prostate cancer cells.
AB - Celastrol has potential application for the treatment of prostate cancer. However
it causes autophagy as a protective response in prostate and other types of
cancers, thus unveiling the underlying mechanisms may benefit its future
application. In the present study, we demonstrate that the miR-17-92a cluster
plays a negative role in celastrol induced-autophagy. Dissection of miR-17-92a
cluster revealed the role of miR-17 seed family (miR-20a and miR-17) in autophagy
inhibition in the context of prostate cancer cells. Autophagy-related gene ATG7
was validated as a target of miR-17 seed family by dual-luciferase assay and
qPCR. Celastrol induced autophagy was inhibited by miR-20a or miR-17, while the
inhibitory effects were rescued in the presence of pcDNA-ATG7 lacking 3' UTR,
demonstrating that these two members target ATG7 to inhibit celastrol-induced
autophagy. As celastrol degrades androgen receptor (AR), a key transcription
factor in prostate cancer cells, we further investigated whether AR affected miR
17-92a expression in prostate cancer cells. AR binding sites were found in the
promoter and two introns of miR-17-92a. In addition, higher expression levels of
miR-17-92a were observed in AR positive cells compared with AR negative cells.
Ectopic expression of AR could enhance the expression of miR-17-92a cluster in AR
negative prostate cancer cells while knockdown of AR decreased miR-17-92a
expression in AR-positive cells, demonstrating the regulation of AR on miR-17-92a
transcription. In summary, our results demonstrate that celastrol downregulates
AR and its target miR-17-92a, leading to autophagy induction in prostate cancer
cells.
PMID- 27501758
TI - Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter
activity.
AB - Endogenous viral elements (EVE) in animal genomes are the fossil records of
ancient viruses and provide invaluable information on the origin and evolution of
extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and
orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital
for viral gene expression and replication. We previously identified in the
budgerigar genome two EVEs that contain the full-length genome of an ancient
budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2
Cp were active in several human and chicken cell lines. A region from nt -85 to
11 in eBHBV1 Cp was critical for the promoter activity. Bioinformatic analysis
revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous
transcription factor, at nt -64 to -50 in eBHBV1 Cp. The NF-Y core binding site
(ATTGG, nt -58 to -54) was essential for eBHBV1 Cp activity. The same results
were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y
(NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated
the promoter activity. Finally, the NF-Y core binding site is conserved in the
Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses.
Interestingly, a putative and functionally important NF-Y core binding site is
located at nt -21 to -17 in the Cp of human hepatitis B virus. In conclusion, our
findings have pinpointed an evolutionary conserved and functionally critical NF-Y
binding element in the Cps of avihepadnaviruses.
PMID- 27501759
TI - Potential mechanisms underlying ectodermal differentiation of Wharton's jelly
mesenchymal stem cells.
AB - Wharton's jelly mesenchymal stem cells (WJMSCs) are being increasingly recognized
for their ectodermal differentiation potential. Previously, we demonstrated that
when WJMSC were seeded onto an acellular matrix material derived from Wharton's
jelly and cultured in osteogenic induction media, generated CK19 positive cells
and hair-like structures indicative of ectodermal differentiation of WJMSCs. In
this manuscript, we examine the underlying mechanism behind this observation
using a variety of microscopy and molecular biology techniques such as western
blotting and qPCR. We demonstrate that these hair-like structures are associated
with live cells that are positive for epithelial and mesenchymal markers such as
cytokeratin-19 and alpha-smooth muscle actin, respectively. We also show that up
regulation of beta-catenin and noggin, along with the expression of TGF-beta and
SMAD and inhibition of BMP4 could be the mechanism behind this ectodermal
differentiation and hair-like structure formation.
PMID- 27501760
TI - Direct induction of hepatocyte-like cells from immortalized human bone marrow
mesenchymal stem cells by overexpression of HNF4alpha.
AB - Hepatocytes from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are
expected to be a useful source for cell transplantation. However, relatively low
efficiency and repeatability of hepatic differentiation of human BM-MSCs remains
an obstacle for clinical translation. Hepatocyte nuclear factor 4 alpha
(HNF4alpha), a critical transcription factor, plays an essential role in the
entire process of liver development. In this study, immortalized hBM-MSCs, UE7T
13 cells were transduced with a lentiviral vector containing HNF4alpha. The
typical fibroblast-like morphology of the MSCs changed, and polygonal,
epithelioid cells grew out after HNF4alpha transduction. In hepatocyte culture
medium, HNF4alpha-transduced MSCs (E7-hHNF4alpha cells) strongly expressed the
albumin (ALB), CYP2B6, alpha-1 antitrypsin (AAT), and FOXA2 mRNA and exhibited
morphology markedly similar to that of mature hepatocytes. The E7-hHNF4alpha
cells showed hepatic functions such as Indocyanine green (ICG) uptake and
release, glycogen storage, urea production and ALB secretion. Approximately 28%
of E7-hHNF4alpha cells expressed both ALB and AAT. Furthermore, these E7
hHNF4alpha cells via superior mesenteric vein (SMV) injection expressed human ALB
in mouse chronic injured liver. In conclusion, this study represents a novel
strategy by directly inducing hepatocyte-like cells from MSCs.
PMID- 27501761
TI - Photochemical Copper Coating on 3D Printed Thermoplastics.
AB - 3D printing using thermoplastics has become very popular in recent years,
however, it is challenging to provide a metal coating on 3D objects without using
specialized and expensive tools. Herein, a novel acrylic paint containing
malachite for coating on 3D printed objects is introduced, which can be
transformed to copper via one-step laser treatment. The malachite containing
pigment can be used as a commercial acrylic paint, which can be brushed onto 3D
printed objects. The material properties and photochemical transformation
processes have been comprehensively studied. The underlying physics of the
photochemical synthesis of copper was characterized using density functional
theory calculations. After laser treatment, the surface coating of the 3D printed
objects was transformed to copper, which was experimentally characterized by XRD.
3D printed prototypes, including model of the Statue of Liberty covered with a
copper surface coating and a robotic hand with copper interconnections, are
demonstrated using this painting method. This composite material can provide a
novel solution for coating metals on 3D printed objects. The photochemical
reduction analysis indicates that the copper rust in malachite form can be
remotely and photo-chemically reduced to pure copper with sufficient photon
energy.
PMID- 27501762
TI - A Versatile and Scalable Approach toward Robust Superhydrophobic Porous Materials
with Excellent Absorbency and Flame Retardancy.
AB - The frequent oil spillages and the industrial discharge of organic contaminants
have not only created severe environmental and ecological crises, but also cause
a risk of fire and explosion. These environmental and safety issues emphasize the
urgent need for materials that possess superior sorption capability and less
flammability and thus can effectively and safely clean up the floating oils and
water-insoluble organic compounds. Here we present the successful hydrophobic
modification of the flame retardant melamine sponge with a commercial
fluorosilicone, by using a facile one-step solvent-free approach and demonstrate
that the resultant superhydrophobic sponge not only exhibits extraordinary
absorption efficiency (including high capacity, superior selectivity, good
recyclability, and simple recycling routes), but also retains excellent flame
retardancy and robust stability. In comparison to conventional methods, which
usually utilize massive organic solvents, the present approach does not involve
any complicated process or sophisticated equipment nor generates any waste
liquids, and thus is a more labor-saving, environment-friendly, energy-efficient
and cost-effective strategy for the hydrophobic modification. Taking into account
the critical role of hydrophobic porous materials, especially in the field of
environmental remediation, the approach presented herein would be highly valuable
for environmental remediation and industrial applications.
PMID- 27501763
TI - Metabolism and excretion of 1-hydroxymethylpyrene, the proximate metabolite of
the carcinogen 1-methylpyrene, in rats.
AB - 1-Methylpyrene, an alkylated polycyclic aromatic hydrocarbon and environmental
carcinogen, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1
HMP) and subsequent sulfo conjugation to the DNA-reactive 1-sulfooxymethylpyrene.
In addition to the bioactivation, processes of metabolic detoxification and
transport greatly influence the genotoxicity of 1-methylpyrene. For a better
understanding of 1-HMP detoxification in vivo we studied urinary and fecal
metabolites in rats following intraperitoneal doses of 19.3mg 1-HMP/kg body
weight (5 rats) or the same dose containing 200MUCi [(14)C]1-HMP/kg body weight
(2 rats). After 48h, 48.0% (rat 1) and 29.1% (rat 2) of the radioactivity was
recovered as 1-HMP in the feces. Six major metabolites were observed by UV and on
line radioactivity detection in urine samples and feces after HPLC separation.
The compounds were characterized by mass spectrometry, (1)H NMR and (1)H-(1)H
COSY NMR spectroscopy, which allowed assigning tentative molecular structures.
Two prominent metabolites, 1-pyrene carboxylic acid (M-6) and the acyl
glucuronide of 1-pyrene carboxylic acid (M-5) accounted for 17.7% (rat 1) and
25.2% (rat 2) of the overall radioactive dose. Further, we detected the acyl
glucuronide of 6-hydroxy-1-pyrene carboxylic acid (M-1) and 8-sulfooxy-1-pyrene
carboxylic acid (M-3) together with two regioisomers of M-3 (M-2 and M-4)
differing in position of the sulfate group at the pyrene ring. In urine samples,
the radioactivity of 1-pyrene carboxylic acid and its five derivatives amounted
to 32.4% (rat 1) or 45.5% (rat 2) of the total [(14)C]1-HMP dose.
PMID- 27501764
TI - Taurine zinc solid dispersions enhance bile-incubated L02 cell viability and
improve liver function by inhibiting ERK2 and JNK phosphorylation during
cholestasis.
AB - Dietary intakes of taurine and zinc are associated with decreased risk of liver
disease. In this study, solid dispersions (SDs) of a taurine zinc complex on
hepatic injury were examined in vitro using the immortalized human hepatocyte
cell line L02 and in a rat model of bile duct ligation. Sham-operated and bile
duct ligated Sprague-Dawley rats were treated with the vehicle alone or taurine
zinc (40, 80, 160mg/kg) for 17days. Bile duct ligation significantly increased
blood lipid levels, and promoted hepatocyte apoptosis, inflammation and
compensatory biliary proliferation. In vitro, incubation with bile significantly
reduced L02 cell viability; this effect was significantly attenuated by
pretreatment with SP600125 (a JNK inhibitor) and enhanced when co-incubated with
taurine zinc SDs. In vivo, administration of taurine zinc SDs decreased serum
alanine aminotransferase and aspartate aminotransferase activities in a dose
dependent manner and attenuated the increases in serum total bilirubin, total
cholesterol and low density lipoprotein cholesterol levels after bile duct
ligation. Additionally, taurine zinc SDs downregulated the expression of
interleukin-1beta and inhibited the phosphorylation of Jun N-terminal kinase
(JNK) and extracellular signal-regulated kinase2 (ERK2) in the liver after bile
duct ligation. Moreover, taurine zinc SDs had more potent blood lipid regulatory
and anti-apoptotic effects than the physical mixture of taurine and zinc acetate.
Therefore, we speculate that taurine zinc SDs protect liver function at least in
part via a mechanism linked to reduce phosphorylation of JNK and ERK2, which
suppresses inflammation, apoptosis and cholangiocyte proliferation during
cholestasis.
PMID- 27501765
TI - Differences in the action of lower and higher chlorinated polychlorinated
naphthalene (PCN) congeners on estrogen dependent breast cancer cell line
viability and apoptosis, and its correlation with Ahr and CYP1A1 expression.
AB - There are data showing that exposition to PCNs mixture increased incidence of
gastrointestinal and respiratory neoplasms, but data regarding incidence of
hormone-dependent cancer so far not shown. The objective was to determine if
exposure to single lower and higher chlorinated PCN congeners is associated with
altered proliferation and apoptosis of estrogen dependent breast cancer cells,
and whether such effects are related to induction of AhR and CYP1A1 protein
expression. MCF-7 cells were exposed to PCN 34, 39, 42, 46, 48, 52, 53, 54, 66,
67, 70, 71, 73 and 74 at concentrations of 100-10,000pg/ml. We evaluated the
action of these PCN congeners on cell proliferation, DNA fragmentation and
caspase-8,-9 activity. AhR and CYP1A1 protein expression and CYP1A1 activity was
evaluated at a concentration of 1000pg/ml. An opposite action of tri- to tetraCNs
than of penta-to heptaCNs on cell proliferation and apoptosis was evident. Tetra
PCNs increased cell proliferation, but had no effect on DNA fragmentation nor
caspase activity. Fast induction of CYP1A1 protein expression under the influence
of lower chlorinated PCNs suggests faster metabolism and a possible stimulatory
action of locally formed metabolites on cell proliferation. None of the higher
chlorinated PCNs affected cell proliferation but all higher chlorinated PCNs
increased caspase-8 activity, and hexa PCNs also increased caspase-9 activity.
The rapid activation of the Ah receptor and CYP1A1 protein expression by higher
chlorinated PCNs point to their toxicity; however, it is not sufficient for
potential carcinogenicity. Action of lower chlorinated naphthalenes metabolites
should be explored.
PMID- 27501766
TI - MicroRNAs as key mediators of hepatic detoxification.
AB - MicroRNAs (miRNAs) are a class of short noncoding RNAs that modulate gene
expression at both transcriptional and post-transcriptional levels. Many studies
have extensively revealed the significance of miRNAs in mediating liver
development and diseases. However, their role in hepatic detoxification processes
has been explored only recently. In this review, we summarized the up-to-date
knowledge about miRNA dependent regulation of enzymes involved in all three
phases of the drugs and xenobiotics detoxification process. We also discussed the
role of miRNA in regulating some upstream nuclear receptors involving gene
expression of enzymes for detoxification process in liver. The toxicological
significance of miRNAs in liver diseases and future research perspectives are
finally presented.
PMID- 27501768
TI - Improvement of outcomes for TP53 carriers.
PMID- 27501767
TI - Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line
treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint
results of a randomised, open-label, non-inferiority, phase 3 trial.
AB - BACKGROUND: The randomised phase 3 TURANDOT trial compared two approved
bevacizumab-containing regimens for HER2-negative metastatic breast cancer in
terms of efficacy, safety, and quality of life. The interim analysis did not
confirm non-inferior overall survival (stratified hazard ratio [HR] 1.04; 97.5%
repeated CI [RCI] -infinity to 1.69). Here we report final results of our study
aiming to show non-inferior overall survival with first-line bevacizumab plus
capecitabine versus bevacizumab plus paclitaxel for locally recurrent or
metastatic breast cancer. METHODS: In this multinational, open-label, randomised
phase 3 TURANDOT trial, patients aged 18 years or older who had an Eastern
Cooperative Oncology Group performance status 0-2 and measurable or non
measurable HER2-negative locally recurrent or metastatic breast cancer who had
received no previous chemotherapy for locally recurrent or metastatic breast
cancer were stratified and randomly assigned (1:1) using permuted blocks of size
six to either bevacizumab plus paclitaxel (bevacizumab 10 mg/kg on days 1 and 15
plus paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 4 weeks) or bevacizumab
plus capecitabine (bevacizumab 15 mg/kg on day 1 plus capecitabine 1000 mg/m(2)
twice daily on days 1-14 every 3 weeks) until disease progression, unacceptable
toxicity, or withdrawal of consent. Stratification factors were oestrogen or
progesterone receptor status, country, and menopausal status. The primary
objective was to show non-inferior overall survival with bevacizumab plus
capecitabine versus bevacizumab plus paclitaxel in the per-protocol population by
rejecting the null hypothesis of inferiority (HR >=1.33) using a stratified Cox
proportional hazard model. This trial is registered with ClinicalTrials.gov,
number NCT00600340. FINDINGS: Between Sept 10, 2008, and Aug 30, 2010, 564
patients were randomised, representing the intent-to-treat population. The per
protocol population comprised 531 patients (266 in the bevacizumab plus
paclitaxel group and 265 in the bevacizumab plus capecitabine group). At the
final overall survival analysis after 183 deaths (69%) in 266 patients receiving
bevacizumab plus paclitaxel and 201 (76%) in 265 receiving bevacizumab plus
capecitabine in the per-protocol population, median overall survival was 30.2
months (95% CI 25.6-32.6 months) versus 26.1 months (22.3-29.0), respectively.
The stratified HR was 1.02 (97.5% RCI -infinity to 1.26; repeated p=0.0070),
indicating non-inferiority. The unstratified Cox model (HR 1.13 [97.5% RCI
infinity to 1.39]; repeated p=0.061) did not support the primary analysis. Intent
to-treat analyses were consistent with the per-protocol results. The most common
grade 3 or worse adverse events were neutropenia (54 [19%] of 284 patients in the
bevacizumab plus paclitaxel group vs 5 [2%] of 277 patients in the bevacizumab
plus capecitabine group), hand-foot syndrome (1 [<1%] vs 43 [16%]), peripheral
neuropathy (39 [14%] vs 1 [<1%]), leucopenia (20 [7%] vs 1 [<1%]), and
hypertension (12 [4%] vs 16 [6%]). Serious adverse events were reported in 65
(23%) of 284 patients receiving bevacizumab plus paclitaxel and 68 (25%) of 277
receiving bevacizumab plus capecitabine. Deaths in two (1%) of 284 patients in
the bevacizumab plus paclitaxel group were deemed by the investigator to be
treatment-related. No treatment-related deaths occurred in the bevacizumab plus
capecitabine group. INTERPRETATION: Bevacizumab plus capecitabine represents a
valid first-line treatment option for HER2-negative locally recurrent or
metastatic breast cancer, offering good tolerability without compromising overall
survival compared with bevacizumab plus paclitaxel. Although progression-free
survival with the bevacizumab plus capecitabine combination is inferior to that
noted with bevacizumab plus paclitaxel, we suggest that physicians should
consider possible predictive risk factors for overall survival, individual's
treatment priorities, and the differing safety profiles. FUNDING: Roche.
PMID- 27501769
TI - Is there room for bevacizumab in metastatic breast cancer?
PMID- 27501770
TI - Biochemical and imaging surveillance in germline TP53 mutation carriers with Li
Fraumeni syndrome: 11 year follow-up of a prospective observational study.
AB - BACKGROUND: Carriers of a germline TP53 pathogenic variant have a substantial
lifetime risk of developing cancer. In 2011, we did a prospective observational
study of members of families who chose to either undergo a comprehensive
surveillance protocol for individuals with Li-Fraumeni syndrome or not. We sought
to update our assessment of and modify the surveillance protocol, so in this
study we report both longer follow-up of these patients and additional patients
who underwent surveillance, as well as update the originally presented
surveillance protocol. METHODS: A clinical surveillance protocol using physical
examination and frequent biochemical and imaging studies (consisting of whole
body MRI, brain MRI, breast MRI, mammography, abdominal and pelvic ultrasound,
and colonoscopy) was introduced at three tertiary care centres in Canada and the
USA on Jan 1, 2004, for carriers of TP53 pathogenic variants. After confirmation
of TP53 mutation, participants either chose to undergo surveillance or chose not
to undergo surveillance. Patients could cross over between groups at any time.
The primary outcome measure was detection of asymptomatic tumours by surveillance
investigations. The secondary outcome measure was 5 year overall survival
established from a tumour diagnosed symptomatically (in the non-surveillance
group) versus one diagnosed by surveillance. We completed survival analyses using
an as-treated approach. FINDINGS: Between Jan 1, 2004, and July 1, 2015, we
identified 89 carriers of TP53 pathogenic variants in 39 unrelated families, of
whom 40 (45%) agreed to surveillance and 49 (55%) declined surveillance. 19 (21%)
patients crossed over from the non-surveillance to the surveillance group, giving
a total of 59 (66%) individuals undergoing surveillance for a median of 32 months
(IQR 12-87). 40 asymptomatic tumours have been detected in 19 (32%) of 59
patients who underwent surveillance. Two additional cancers were diagnosed
between surveillance assessments (false negatives) and two biopsied lesions were
non-neoplastic entities on pathological review (false positives). Among the 49
individuals who initially declined surveillance, 61 symptomatic tumours were
diagnosed in 43 (88%) patients. 21 (49%) of the 43 individuals not on
surveillance who developed cancer were alive compared with 16 (84%) of the 19
individuals undergoing surveillance who developed cancer (p=0.012) after a median
follow-up of 46 months (IQR 22-72) for those not on surveillance and 38 months
(12-86) for those on surveillance. 5 year overall survival was 88.8% (95% CI 78.7
100) in the surveillance group and 59.6% (47.2-75.2) in the non-surveillance
group (p=0.0132). INTERPRETATION: Our findings show that long-term compliance
with a comprehensive surveillance protocol for early tumour detection in
individuals with pathogenic TP53 variants is feasible and that early tumour
detection through surveillance is associated with improved long-term survival.
Incorporation of this approach into clinical management of these patients should
be considered. FUNDING: Canadian Institutes for Heath Research, Canadian Cancer
Society, Terry Fox Research Institute, SickKids Foundation, and Soccer for Hope
Foundation.
PMID- 27501771
TI - Differences in metabolic biomarkers in the blood and gene expression profiles of
peripheral blood mononuclear cells among normal weight, mildly obese and
moderately obese subjects.
AB - We compared metabolic biomarkers in the blood and peripheral blood mononuclear
cell (PBMC) gene expression profiles among normal weight (BMI, 18.5-23 kg/m2),
mildly obese (BMI, 25-27.5 kg/m2) and moderately obese Korean adult men (BMI,
27.5-30 kg/m2). High leptin, lipids (except LDL- and HDL-cholesterol) and apoB
levels and low adiponectin and HDL-cholesterol levels were present in the plasma
of both mildly and moderately obese subjects. Circulating levels of inflammatory
cytokines and markers of insulin resistance, oxidative stress and liver damage
were altered in moderately obese subjects but not in mildly obese subjects. PBMC
transcriptome data showed enrichment of pathways involved in energy metabolism,
insulin resistance, bone metabolism, cancer, inflammation and fibrosis in both
mildly and moderately obese subjects. Signalling pathways involved in oxidative
phosphorylation, TAG synthesis, carbohydrate metabolism and insulin production;
mammalian target of rapamycin, forkhead box O, ras-proximate-1, RAS and
transforming growth factor-beta signalling; as well as extracellular matrix
receptor interaction were enriched only in moderately obese subjects, indicating
that changes in PBMC gene expression profiles, according to metabolic
disturbances, were associated with the development and/or aggravation of obesity.
In particular, fourteen and fifteen genes differentially expressed only in mildly
obese subjects and in both mildly and moderately obese subjects, respectively,
could be used as early or stable biomarkers for diagnosing and treating obesity
associated metabolic disturbance. We characterised BMI-associated metabolic and
molecular biomarkers in the blood and provided clues about potential blood-based
targets for preventing or treating obesity-related complications.
PMID- 27501772
TI - Plasma Inflammatory Cytokine IL-4, IL-8, IL-10, and TNF-alpha Levels Correlate
with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary
Disease (COPD) Overlap Syndrome.
AB - BACKGROUND The aim of this study was to investigate the plasma inflammatory
cytokine levels and their correlations with pulmonary function in patients with
asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS). MATERIAL
AND METHODS Between January 2013 and December 2014, a total of 96 patients with
asthma, acute exacerbation of chronic obstructive pulmonary disease (AECOPD), or
ACOS were enrolled, and 35 healthy people were included as a control group.
Fasting plasma interleukin (IL)-4, IL-8, IL-10, and tumor necrosis factor alpha
(TNF-alpha) levels were detected using enzyme-linked immunosorbent assay (ELISA).
Correlations between the plasma inflammatory cytokine levels and forced
expiratory volume in 1 second (FEV1), FEV1/predicted value ratio (FEV1%pred), and
FEV1/forced vital capacity (FVC) were analyzed. RESULTS IL-4 and IL-8 levels
showed statistically significant differences among the 3 groups of patients (both
P<0.001); IL-4 level was significantly lower, while IL-8 level was significantly
higher in the AECOPD group and ACOS group than those in the asthma group (all
P<0.05). IL-10 level and TNF-alpha level were significantly different among the 3
patient groups (both P<0.001). IL-10 level was significantly different between
each of the 2 groups (all P<0.001). TNF-alpha level in the asthma group was
higher than in the AECOPD group and ACOS group (both P<0.001). IL-4 and IL-10
were positively and IL-8 and TNF-alpha were negatively related with FEV1,
FEV1%pred, and FEV1/FVC. CONCLUSIONS Plasma levels of inflammatory cytokines IL
4, IL-8, IL-10, and TNF-alpha are related with severity of airway diseases and
could be potential markers for the evaluation of asthma, COPD, and ACOS.
PMID- 27501773
TI - Thyroid hormones are essential to preserve non-proliferative cells of adult
neurogenesis of the dentate gyrus.
AB - Thyroid hormones (THs) regulate adult hippocampal neurogenesis, a process that
involves both cell populations that dynamically switch between pools of
proliferative and quiescent cells, and cells that definitely leave the cell cycle
to maturate into granular neurons. This investigation was carried out to
determine the role of THs on the mitotic activity of specific proliferative cell
populations and the preservation of non-proliferative cells participating in the
neurogenic process of the dentate gyrus (DG) of the hippocampus. Hypothyroidism
was induced in male adult Wistar rats with methimazole for 28days. We quantified
the total number of proliferative cells (BrdU+), proliferative type 1
(BrdU+/GFAP+), and 2b and 3 (BrdU+/DCX+) cells. Early non-proliferative cells
(BrdU-/DCX+ cells lacking dendritic process), postmitotic neuroblasts (Tuj 1+
cells lacking dendritic process), and immature granular neurons (IGN; DCX+ or Tuj
1+ and the presence of dendritic processes into granular or molecular layer) were
also included. The evidence showed that the proliferation of Type 1, 2b and 3
cells is not modified by hypothyroidism. In contrast, hypothyroidism reduced the
number of early non-proliferative cells and also leads to a decrement in the
number of IGN. Our results show that proliferative cells of the DG are not
sensitive to thyroid perturbations. However, THs are essential to preserve cell
populations that leave the cell cycle in the DG of the hippocampus.
PMID- 27501774
TI - Genome-Wide Transcriptome and Binding Sites Analyses Identify Early FOX
Expressions for Enhancing Cardiomyogenesis Efficiency of hESC Cultures.
AB - The differentiation efficiency of human embryonic stem cells (hESCs) into heart
muscle cells (cardiomyocytes) is highly sensitive to culture conditions. To
elucidate the regulatory mechanisms involved, we investigated hESCs grown on
three distinct culture platforms: feeder-free Matrigel, mouse embryonic
fibroblast feeders, and Matrigel replated on feeders. At the outset, we profiled
and quantified their differentiation efficiency, transcriptome, transcription
factor binding sites and DNA-methylation. Subsequent genome-wide analyses allowed
us to reconstruct the relevant interactome, thereby forming the regulatory basis
for implicating the contrasting differentiation efficiency of the culture
conditions. We hypothesized that the parental expressions of FOXC1, FOXD1 and
FOXQ1 transcription factors (TFs) are correlative with eventual cardiomyogenic
outcome. Through WNT induction of the FOX TFs, we observed the co-activation of
WNT3 and EOMES which are potent inducers of mesoderm differentiation. The result
strengthened our hypothesis on the regulatory role of the FOX TFs in enhancing
mesoderm differentiation capacity of hESCs. Importantly, the final proportions of
cells expressing cardiac markers were directly correlated to the strength of FOX
inductions within 72 hours after initiation of differentiation across different
cell lines and protocols. Thus, we affirmed the relationship between early FOX TF
expressions and cardiomyogenesis efficiency.
PMID- 27501775
TI - Inhibition of Mycobacterium tuberculosis dihydrodipicolinate synthase by alpha
ketopimelic acid and its other structural analogues.
AB - The Mycobacterium tuberculosis dihydrodipicolinate synthase (Mtb-dapA) is an
essential gene. Mtb-DapA catalyzes the aldol condensation between pyruvate and L
aspartate-beta-semialdehyde (ASA) to yield dihydrodipicolinate. In this work we
tested the inhibitory effects of structural analogues of pyruvate on recombinant
Mtb-DapA (Mtb-rDapA) using a coupled assay with recombinant dihydrodipicolinate
reductase (Mtb-rDapB). Alpha-ketopimelic acid (alpha-KPA) showed maximum
inhibition of 88% and IC50 of 21 MUM in the presence of pyruvate (500 MUM) and
ASA (400 MUM). Competition experiments with pyruvate and ASA revealed competition
of alpha-KPA with pyruvate. Liquid chromatography-mass spectrometry (LC-MS) data
with multiple reaction monitoring (MRM) showed that the relative abundance peak
of final product, 2,3,4,5-tetrahydrodipicolinate, was decreased by 50%. Thermal
shift assays showed 1 degrees C Tm shift of Mtb-rDapA upon binding alpha-KPA.
The 2.4 A crystal structure of Mtb-rDapA-alpha-KPA complex showed the interaction
of critical residues at the active site with alpha-KPA. Molecular dynamics
simulations over 500 ns of pyruvate docked to Mtb-DapA and of alpha-KPA-bound Mtb
rDapA revealed formation of hydrogen bonds with pyruvate throughout in contrast
to alpha-KPA. Molecular descriptors analysis showed that ligands with polar
surface area of 91.7 A(2) are likely inhibitors. In summary, alpha-hydroxypimelic
acid and other analogues could be explored further as inhibitors of Mtb-DapA.
PMID- 27501776
TI - Radiation-induced changes in intestinal and tissue-nonspecific alkaline
phosphatase: implications for recovery after radiation therapy.
AB - BACKGROUND: Exogenous replacement of depleted enterocyte intestinal alkaline
phosphatase (IAP) decreases intestinal injury in models of colitis. We determined
whether radiation-induced intestinal injury could be mitigated by oral IAP
supplementation and the impact on tissue-nonspecific AP. METHODS: WAG/RjjCmcr
rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by
daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real
time polymerase chain reaction, AP activity, and microbiota analysis were
performed on intestine. Lipopolysaccharide and cytokine analysis was performed on
serum. Data were expressed as a mean +/- SEM with P greater than .05 considered
significant. RESULTS: Intestine of irradiated animals demonstrates lower hemibody
irradiation and is associated with upregulation of tissue-nonspecific AP,
downregulation of IAP, decreased AP activity, and altered composition of the
intestinal microbiome. CONCLUSIONS: Supplemental IAP after radiation may be
beneficial in mitigating intestinal radiation syndrome as evidenced by improved
histologic injury, decreased acute intestinal inflammation, and normalization of
intestinal microbiome.
PMID- 27501777
TI - High-Density Protein Loading on Hierarchically Porous Layered Double Hydroxide
Composites with a Rational Mesostructure.
AB - Hierarchically porous biocompatible Mg-Al-Cl-type layered double hydroxide (LDH)
composites containing aluminum hydroxide (Alhy) have been prepared using a phase
separation process. The sol-gel synthesis allows for the hierarchical pores of
the LDH-Alhy composites to be tuned, leading to a high specific solid surface
area per unit volume available for high-molecular-weight protein adsorptions. A
linear relationship between the effective surface area, SEFF, and loading
capacity of a model protein, bovine serum albumin (BSA), is established following
successful control of the structure of the LDH-Alhy composite. The threshold of
the mean pore diameter, Dpm, above which BSA is effectively adsorbed on the
surface of LDH-Alhy composites, is deduced as 20 nm. In particular, LDH-Alhy
composite aerogels obtained via supercritical drying exhibit an extremely high
capacity for protein loading (996 mg/g) as a result of a large mean mesopore
diameter (>30 nm). The protein loading on LDH-Alhy is >14 times that of a
reference LDH material (70 mg/g) prepared via a standard procedure. Importantly,
BSA molecules pre-adsorbed on porous composites were successfully released on
soaking in ionic solutions (HPO4(2-) and Cl(-) aqueous). The superior capability
of the biocompatible LDH materials for loading, encapsulation, and releasing
large quantities of proteins was clearly demonstrated.
PMID- 27501778
TI - Larvicidal activity of natural and modified triterpenoids against Aedes aegypti
(Diptera: Culicidae).
AB - BACKGROUND: Insecticide resistance to commonly used substances demands new
molecules for the chemical control of the dengue vector Aedes aegypti. Because
natural product sources have been an alternative to obtain larvicidal compounds,
the aim of this study was to evaluate the triterpenoids betulinic (BA) and
ursolic (UA) acids and their semi-synthetic derivatives against larval Ae.
aegypti. BA, UA, ten derivatives modified at the C-3 position and a positive
control (diflubenzuron) were evaluated. Larvicidal assays were carried out with
early fourth-instar larvae, and mortality was observed between 48 and 96 h. Doses
from 200 to 10 ppm were used to calculate lethal concentrations (LCs). RESULTS:
Natural compounds, i.e. UA and BA, had the lowest LCs (LC50 of 112 and 142 ppm
respectively), except for the modified compound 2b (LC50 of 130 ppm). Larvicidal
activity increased significantly from 48 to 96 h for all the compounds evaluated,
ranging from 20 to 50% after 48 h and from 48 to 76% after 96 h. Some
derivatives, e.g. 2a and 2d, had up to a three-fold larvicidal activity increase
from 48 to 96 h. CONCLUSION: BA, UA and their derivatives showed larvicidal
activity against Ae. aegypti larvae, increasing significantly from 48 to 96 h.
The presence of a hydroxyl group is essential for larvicidal potential in these
triterpenoids. (c) 2016 Society of Chemical Industry.
PMID- 27501779
TI - Target-controlled gating liposome "off-on" cascade amplification for sensitive
and accurate detection of phospholipase D in breast cancer cells with a low
background signal.
AB - Here we developed a simple, sensitive and accurate PLD detection method based on
a target-controlled gating liposome (TCGL) "off-on" cascade amplified strategy
and personal glucose meters (PGMs). It showed excellent sensitivity with a
detection limit of 0.005 U L(-1) and well performed PLD activity analysis in
breast cancer cells and inhibitor drug screening.
PMID- 27501780
TI - Protein phosphatase 5 mediates corticosteroid insensitivity in airway smooth
muscle in patients with severe asthma.
AB - BACKGROUND: The mechanisms driving glucocorticoid (GC) insensitivity in patients
with severe asthma are still unknown. Recent evidence suggests the existence of
GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC
receptor (GRalpha) function. We examined whether other mechanisms could
potentially explain the reduced sensitivity of ASM cells to GC in severe
asthmatics. METHODS: Airway smooth muscle cells from healthy and severe asthmatic
subjects were treated with TNF-alpha and responses to corticosteroids in both
cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time
PCR. Immunohistochemistry and flow cytometry assays were used to assess the
expression of the protein phosphatase PP5 in endobronchial biopsies and ASM
cells. RESULTS: The production of CCL11 and CCL5 by TNF-alpha was insensitive to
both fluticasone and dexamethasone in ASM cells from severe asthmatic compared to
that in healthy subjects. Fluticasone-induced GRalpha nuclear translocation,
phosphorylation at serine 211 and expression of GC-induced leucine zipper (GILZ)
were significantly reduced in ASM cells from severe asthmatics compared to
responses in healthy subjects. Levels of PP5 were increased in ASM cells from
severe asthmatics and PP5 knockdown using siRNA restored fluticasone repressive
action on chemokine production and its ability to induce GRalpha nuclear
translocation and GRE-dependent GILZ expression. In vivo PP5 expression was also
increased in the ASM bundles in endobronchial biopsies in severe asthmatics.
CONCLUSIONS: PP5-dependent impairment of GRalpha function represents a novel
mechanism driving GC insensitivity in ASM in severe asthma.
PMID- 27501783
TI - Nutrition Transition and Obesity Among Teenagers and Young Adults in South Asia.
AB - INTRODUCTION: Obesity among teenagers/adolescents and young adults is associated
with significant adverse short and longer-term effects on health. To date, no
narrative reviews have evaluated nutrition transition and its contribution to the
obesity epidemic among adolescents and young adults in the South Asian (SA)
region. METHOD: Data were retrieved by a four-stage systematic search process. A
search of the online Pub- Med/Medline, SciVerse Scopus and Web of Science
databases was performed. The age groups were defined as follows; teenage:13-19
years, adolescence:10-18 years and young adult:19-24 years. RESULTS: Among
teenagers/adolescents, the prevalence of overweight ranged from 11.0% (Sri Lanka)
to 19.0% (India), while obesity ranged from 2.4% (Sri Lanka) to 11.0% (Pakistan).
In young adults, prevalence of overweight ranged between 7.9% (Nepal) to 15.0%
(Pakistan), while obesity showed a much wider variation (0.005%[Nepal] -
22.8%[India]). Nutritional risk factors associated with overweight/ obesity among
SAs of this age group included reduced fruit and vegetable consumption, a total
vegetarian diet, consumption of fast food and soft drinks, and skipping
breakfast. Other contributing factors identified were: adding extra salt to
meals, eating meals outside of the home, frequently visiting restaurants and
eating while watching television. Daily milk/yoghurt consumption and a family
supper have shown a protective effect against overweight/obesity. CONCLUSION:
Overweight and obesity are common amongst teenagers/adolescents and young adults
of the SA region. Several food types and habits were identified as being
associated with overweight/ obesity in this population. Identifying common
protective and contributory factors is very important for the development of a
shared regional preventive strategy.
PMID- 27501782
TI - Transplantation of Human Placenta-Derived Mesenchymal Stem Cells Alleviates
Critical Limb Ischemia in Diabetic Nude Rats.
AB - Neovasculogenesis induced by stem cell therapy is an innovative approach to
improve critical limb ischemia (CLI) in diabetes. Mesenchymal stem cells (MSCs)
are ideal candidates due to their angiogenic and immunomodulatory features. The
aim of this study is to determine the therapeutic effects of human placenta
derived MSCs (P-MSCs) on diabetic CLI, with or without exogenous insulin
administration, and the underlying mechanism of any effect. A series of in vitro
experiments were performed to assess the stemness and vasculogenic activity of P
MSCs. P-MSCs were intramuscularly injected at two different doses with and
without the administration of insulin. The efficacy of P-MSC transplantation was
evaluated by ischemia damage score, ambulatory score, laser Doppler perfusion
image (LDPI), capillary, and vascular density. In vivo imaging was applied to
track the implanted P-MSCs. In vivo differentiation and in situ secretion of
angiogenic cytokines were determined. In vitro experimental outcomes showed the
differentiation potential and potent paracrine effect of P-MSCs. P-MSCs survived
in vivo for at least 3 weeks and led to the acceleration of ischemia recovery,
due to newly formed capillaries, increased arterioles, and secretion of various
proangiogenic factors. P-MSCs participate in angiogenesis and vascularization
directly through differentiation and cytokine expression.
PMID- 27501781
TI - Association of variations in HLA class II and other loci with susceptibility to
EGFR-mutated lung adenocarcinoma.
AB - Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East
Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic
factors underlying the risk of this disease by conducting a genome-wide
association study, followed by two validation studies, in 3,173 Japanese patients
with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci,
5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown
to be strongly associated with overall lung adenocarcinoma risk in East Asians,
were re-discovered as loci associated with a higher susceptibility to EGFR
mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA
class II at 6p21.32 (rs2179920; P =5.1 * 10(-17), per-allele OR=1.36) and 6p21.1
(FOXP4) (rs2495239; P=3.9 * 10(-9), per-allele OR=1.19) were newly identified as
loci associated with EGFR mutation-positive lung adenocarcinoma. This study
indicates that multiple genetic factors underlie the risk of lung adenocarcinomas
with EGFR mutations.
PMID- 27501784
TI - Dietary Fats and Oils in India.
AB - BACKGROUND: India is undergoing rapid nutrition transition concurrent with an
increase in obesity, metabolic syndrome, and type 2 diabetes (T2DM). There is a
shift from a healthy traditional home-cooked high-fiber, low-fat, low-calorie
diet, towards increasing consumption of packaged, ready-to-eat foods which are
calorie-dense and contain refined carbohydrates, high fat, salt and sugar; and
less fiber. Although fats and oils have been an integral part of our diets, there
is a change in the pattern of consumption, in terms of both quality and quantity.
METHODS: A literature search was conducted using the terms "fats, oil consumption
in India, effects of vegetable oils, obesity and T2DM in Indians" in the medical
search database PubMed (National Library of Medicine, Bethesda, MD, USA) from
1966 to June 2016. A manual search of the relevant quoted references was also
carried out from the retrieved articles. Data have also been taken from
nutritional surveys in India and worldwide, websites and published documents of
the World Health Organization, the Food and Agricultural Organization, National
Sample Survey Organization and websites of industries related to oil production.
CONCLUSION: Increasing use of saturated fat, low intake of n-3 poly unsaturated
fatty acids and increase in trans-fatty acids, along with increasing intake of
dietary sugars has been noted in India. Most importantly, traditional false
beliefs and unawareness about health effects of oils continues to be prevalent.
Aggressive public health awareness programs coupled with governmental action and
guidelines tailored for Indian population are required, to promote less
consumption of fats and oils, use of healthy oils and fats, decreased intake of
saturated fats and trans fatty acids, and increase intake of n-3 Poly-unsaturated
fatty acids and mono-unsaturated fatty acids.
PMID- 27501785
TI - Overdiagnosis, medicalisation and social justice: commentary on Carter et al
(2016) 'A definition and ethical evaluation of overdiagnosis'.
PMID- 27501786
TI - Back to the bedside? Making clinical decisions in patients with prolonged
unconsciousness.
AB - In 1993, the UK High Court decided that Tony Bland was unaware of himself and his
environment, had no interest in medical treatment and allowed withdrawal of
treatment. Subsequently, the court has reviewed all cases of stopping feeding and
hydration in people with a prolonged disorder of consciousness. Their focus has
been on determining whether the person is in the permanent vegetative state,
because this avoids considering what is in a person's Best Interests.
Consequently, much resource is spent distinguishing the vegetative state from the
minimally conscious state and often clinical decisions are delayed or not made
because of the requirement to go to court. In this paper, I argue that the
neurophysiological basis of consciousness is unknown, and one cannot test whether
the necessary structures are functioning. Unconscious people have responsiveness
which varies; they may even have brief behaviours suggestive of awareness. No
single clinical sign or investigation nor assessment battery can prove the
presence (or absence) of consciousness or its permanence. The diagnosis of
consciousness is clinical. Furthermore, awareness varies across a spectrum. There
is no separate vegetative state. People simply have very limited or absent
awareness. Even if there were such a state, it cannot be identified. The ethical
and legal issues associated with decisions on treatment of unconscious people are
no different from similar decisions in other patients. All decisions should be
taken within the Best Interests framework and process. There should be no
requirement to take any particular decision to court in this patient group.
PMID- 27501787
TI - Casting the net too wide on overdiagnosis: benefits, burdens and non-harmful
disease.
PMID- 27501788
TI - Why do parents decline newborn intramuscular vitamin K prophylaxis?
AB - OBJECTIVE: To explore the influencing factors and reasoning of parents who opt
out of intramuscular vitamin K prophylaxis for their newborn. DESIGN: We
conducted a qualitative study with 15 families from the Otago/Southland region of
New Zealand. Semistructured interviews explored their choice to opt out of
intramuscular vitamin K prophylaxis and thematic analysis was used to elucidate
themes that captured important aspects of this parental decision-making process.
RESULTS: Parents opt out of intramuscular vitamin K for a variety of reasons.
These were clustered into three main themes: parents' beliefs and values
(philosophy and spirituality), concerns about their child's welfare (pain and
potential side effects) and external influencing factors (family, friends, media
and health professionals). As part of a wider family hesitancy towards medical
intervention, the majority of parents also raised concerns regarding other
perinatal or childhood interventions. CONCLUSION: Many factors influence parental
decision making and lead to a decision to opt out of newborn intramuscular
vitamin K prophylaxis. Due to strong parallels with other common childhood
interventions, these findings have relevance for vitamin K prophylaxis and for
other healthcare interventions in childhood.
PMID- 27501789
TI - Challenges in diagnosis and management of giant solitary fibrous tumour of
pleura: a case report.
AB - BACKGROUND: Majority of patients with solitary fibrous tumours of the pleura
(SFTP) are asymptomatic. Acute presentation with symptoms resulting from mass
effect due to rapid expansion of tumour size has not been reported before. CASE
PRESENTATION: This report chronicles the case of a giant SFTP in a 76-year-old
lady who presented with acute onset of haemoptysis, left-sided pleuritic chest
pain and hoarseness of voice. Her chest radiograph showed a large left upper
hemithorax mass with an ipsilateral effusion. Computed tomography (CT) scan of
the thorax confirmed the presence of a pleural-based mass lesion in the left apex
measuring 9.7 cm with close apposition to the aortic arch. The mass demonstrated
neovascularization and there was also presence of a moderate-sized heterogeneous
appearing left pleural effusion. Thoracocentesis yielded deeply haemoserous
pleural fluid with a pleural aspirate hematocrit closely approaching that of
peripheral blood hematocrit and alongside a 2 unit decrease in haemoglobin, was
indicative of a haemothorax. Repeat CT 10 days from initial presentation showed
reduction in size of the left apical mass as well as resolution of the left
effusion. This was consistent with the occurrence of an intra-tumoural bleed
resulting in rapid increase in the size of the SFTP, causing rupture of
superficial blood vessels on the tumour surface (haemothorax) and consequential
compression of the lung parenchyma (haemoptysis) and left recurrent laryngeal
nerve (hoarseness of voice). The patient eventually underwent an uneventful
surgical resection. CONCLUSION: A benign SFTP can present acutely with
compressive symptoms as a result of spontaneous intra-tumoural bleed causing
sudden increase in its size. It is important to allow temporal regression of
these acute changes before deciding on surgical resectability.
PMID- 27501790
TI - Assessment of prison life of persons with disability in Ghana.
AB - BACKGROUND: Persons with Disabilities (PWDs) are a unique group that are often
overlooked in many developing countries due to systemic weaknesses, lack of
political commitment and inadequate support from government and non-governmental
agencies. The population of these individuals is however steadily on the increase
and currently corresponds to 15 % of the world population. Although much data
exist on lifestyle and conditions of prisoners with disabilities in the western
world, scanty information is available in Africa. In Ghana, there is insufficient
data on the occurrence and social characteristics of prisoners with disabilities.
The purpose of this current study was therefore to identify the occurrence, types
and causes of disabilities among prisoners serving sentences in Ghanaian prisons.
METHODS: This study was a descriptive cross-sectional survey conducted in the
Male and Female Regional Prisons in Kumasi, Sunyani and the Nsawam Medium
Security Prison, from November to December 2011. PWDs were selected by prisons
officers and interviewed using structured questionnaires on variables such as
socio-demographic characteristics, causes of disabilities and accessibility to
recreational facilities. Ethical approval was obtained from the security services
and the Committee of Human Research Publications and Ethics (CHRPE) of the School
of Medical Sciences, Kwame Nkrumah University of Science and Technology (KNUST).
RESULTS: We screened 6114 records of prisoners of which 1852 (30.3 %) were from
the Kumasi Central Prisons, 3483 (57 %) from the Nsawam Medium Security and 779
(12.8 %) from the Sunyani Central Prisons. A total of 99 PWDs were identified
with the commonest disability being physical, followed by visual, hearing,
speech, mental and albinism. Most of the disabilities were caused by trauma (68.8
%) followed by infection (16.7 %), and drug related mental disabilities (6.3 %).
Fifty (50.5 %) out of the 99 PWDs were not provided with assistive devices
although they admitted the need for such. CONCLUSION: The present study has
demonstrated the occurrence and conditions of PWDs in Ghanaian prisons. Major
stakeholders including government agencies and other organisations could develop
policies that would improve the conditions and livelihood of prisoners with
disabilities in Ghana.
PMID- 27501792
TI - Counter-clockwise vortical blood flow in the main pulmonary artery in a patient
with patent ductus arteriosus with pulmonary arterial hypertension: a cardiac
magnetic resonance imaging case report.
AB - BACKGROUND: In patients with pulmonary hypertension (PH), duration of vortical
blood flow along the main pulmonary artery enables estimation of the mean
pulmonary arterial pressure (mPAP) non-invasively. It remains to date not known,
if this method is applicable in patients with pulmonary arterial hypertension
(PAH) and abnormal aortic-to-pulmonary shunting. CASE PRESENTATION: The present
case analyzes the effect of a patent ductus arteriosus (PDA) on pulmonary artery
flow patterns in PAH (mPAP from right heart catheterization, 75 mmHg). PH
associated vortical blood flow, which is typically observed rotating in a
clockwise direction when viewed in right ventricular outflow tract orientation,
was found nested in PDA left-to-right shunting. Even though rotating counter
clockwise, duration of vortical flow translated into correct non-invasive mPAP
estimate. CONCLUSIONS: This case indicates that PH-associated vortex rotation is
not restricted to clockwise direction, and that vortex-based estimation of
elevated mPAP might also be feasible in patients with PAH and PDA.
PMID- 27501791
TI - Transcriptome analysis of seed dormancy after rinsing and chilling in ornamental
peaches (Prunus persica (L.) Batsch).
AB - BACKGROUND: Ornamental peaches cv. 'Yaguchi' (Prunus persica (L.) Batsch) can be
propagated via seeds. The establishment of efficient seed treatments for early
germination and seedling growth is required to shorten nursery and breeding
periods. It is important, therefore, to identify potential candidate genes
responsible for the effects of rinsing and chilling on seed germination. We
hypothesized that longer rinsing combined with chilling of seeds can alter the
genes expression in related to dormancy and then raise the germination rate in
the peach. To date, most molecular studies in peaches have involved structural
genomics, and few transcriptome studies of seed germination have been conducted.
In this study, we investigated the function of key seed dormancy-related genes
using next-generation sequencing to profile the transcriptomes involved in seed
dormancy in peaches. De novo assembly and analysis of the transcriptome
identified differentially expressed and unique genes present in this fruit.
RESULTS: De novo RNA-sequencing of peach was performed using the Illumina Miseq
2000 system. Paired-end sequence from mRNAs generated high quality sequence reads
(9,049,964, 10,026,362 and 10,101,918 reads) from 'Yaguchi' peach seeds before
rinsed (BR) and after rinsed for 2 or 7 days with a chilling period of 4 weeks
(termed 2D4W and 7D4W), respectively. The germination rate of 7D4W was
significantly higher than that of 2D4W. In total, we obtained 51,366 unique
sequences. Differential expression analysis identified 7752, 8469 and 506
differentially expressed genes from BR vs 2D4W, BR vs 7D4W and 2D4W vs 7D4W
libraries respectively, filtered based on p-value and an adjusted false discovery
rate of less than 0.05. This study identified genes associated with the rinsing
and chilling process that included those associated with phytohormones, the
stress response and transcription factors. 7D4W treatment downregulated genes
involved in ABA synthesis, catabolism and signaling pathways, which eventually
suppressed abscisic acid activity and consequently promoted germination and
seedling growth. Stress response genes were also downregulated by the 7D4W
treatment, suggesting that this treatment released seeds from endodormancy.
Transcription factors were upregulated by the BR and 2D4W treatment, suggesting
that they play important roles in maintaining seed dormancy. CONCLUSIONS: This
work indicated that longer rinsing combined with chilling affects gene expression
and germination rate, and identified potential candidate genes responsible for
dormancy progression in seeds of 'Yaguchi' peach. The results could be used to
develop breeding programs and will aid future functional genomic research in
peaches and other fruit trees.
PMID- 27501793
TI - Pazolimus: pazopanib plus sirolimus following progression on pazopanib, a
retrospective case series analysis.
AB - BACKGROUND: To explore the activity of pazopanib (P) + sirolimus (S) in patients
who progressed after previous clinical benefit on pazopanib. METHODS: Eight
patients with progressing metastatic high grade soft tissue sarcoma (STS) whose
disease advanced on P following a response duration of at least 4 months were
offered re-challenge of P supplemented by off-label S and a single patient with
progressing metastatic chondrosarcoma was offered the combination as
compassionate treatment. Patients were treated in two centers: Hadassah Medical
Center and Tel Aviv Medical Center. Patients received oral P 200-600 mg once a
day supplemented by S 3-4 mg taken separately, 12 h after the P dose. RESULTS:
Patients received treatment from December 2012 to February 2016. Four progressed
on the combination and their treatment was terminated. Two patients were
undergoing treatment when data was summarized. Best Response Evaluation Criteria
in Solid Tumour (RECIST) responses were: one partial response (PR), four stable
disease (SD), and four progressive disease (PD), corresponding to five PR and
four PD on the Choi criteria. Median progression free survival was 5.5 months
(range 4-17). CONCLUSIONS: Our series showed that the combination of P + S has
activity in STS patients selected by previous response to P and in a patient with
chondrosarcoma, suggesting this can serve as a mechanism to reverse resistance to
P and extend the chemotherapy-free window.
PMID- 27501795
TI - Reply to Letter to Editor: Management of Suprahepatic Inferior Vena Cava
Obstruction.
PMID- 27501796
TI - 23 Lung Metastases Treated by Radiofrequency Ablation Over 10 Years in a Single
Patient: Successful Oncological Outcome of a Metastatic Cancer Without Altered
Respiratory Function.
AB - An 82-year-old man, who was diagnosed in 2002 with an oncocytic (Hurthle cell)
thyroid carcinoma, was initially treated by local surgery and was refractory to
radioiodine treatment. The patient had successive secondary recurrences from 2006
onwards. Metastases were suspected due to an elevation of thyroglobulin in serum.
Hypermetabolic nodules were targeted using FDG PET as well as CT-guided
radiofrequency ablations. Thyroglobulin levels decreased following each
procedure. 10 years later, tolerance and efficacy are excellent; 23 lung
metastases have been treated during 11 sessions without current relapse.
Respiratory function and quality of life are not altered. This report illustrates
how radiofrequency ablation can be efficiently integrated into the long-term
management of poorly aggressive oligometastatic cancer, in combination with other
local and/or systemic therapies.
PMID- 27501797
TI - Regarding "Amplatzer Vascular Plugs Versus Coils for Embolization of Pulmonary
Arteriovenous Malformations in Patients with Hereditary Hemorrhagic
Telangiectasia".
PMID- 27501798
TI - Management of Suprahepatic Inferior Vena Cava Obstruction.
PMID- 27501799
TI - Patient factors associated with initiation of behavioral weight loss treatment: a
prospective observational study in an integrated care setting.
AB - Low enrollment in behavioral weight loss treatments limits their impact. We aimed
to identify factors associated with treatment initiation. The participants were
outpatients (n = 198) at Veterans Affairs (VA) healthcare facilities who were
referred to a free VA-based behavioral weight loss treatment. Participants were
assessed on psychosocial factors potentially relevant to treatment initiation.
Subsequent treatment initiation was determined via medical record review. Study
participants were 77 % male, 60 % African American, and 54 % initiated treatment.
In multivariable analyses, treatment initiation was associated with being single,
higher anxiety, and patients' perceptions that referring provider supported their
weight autonomy. Endorsement of treatment barriers was not associated with
treatment initiation. Treatments offering in-person sessions and mood management
components were rated as more preferred. Initiation of behavioral weight loss
treatments may increase if patients believe that providers respect their weight
control autonomy and if healthcare organizations offer treatments that match
patients' preferences.
PMID- 27501801
TI - Erratum to: Transitional Progenitors during Vertebrate Retinogenesis.
PMID- 27501800
TI - [Chronic low back pain and psychological comorbidity : A review].
AB - BACKGROUND: Back pain is a common, disabling problem in Germany. Previous
research has evaluated associations between low back pain (LBP), depression, and
fear. OBJECTIVES: The results should provide ideas of how to optimize preventive
measures, give guidelines for rehabilitation of patients with LBP, and to develop
new therapies. MATERIALS AND METHODS: A systematic review of the literature
including primary publications and meta-analyses using set search criteria in
PubMed was performed. A meta-analysis was then done. RESULTS: In all, 34 studies
met the inclusion and quality criteria, whereby 14 studies were included in the
meta-analysis. In the literature, significantly different depression scores were
reported for people with LBP compared to a healthy control group. The pain
perception in persons with LBP is associated with depression and fear. The
correlation between depression and pain perception was highly significant in 5
studies (p < 0.01) and significant in 8 studies (p < 0.05). Fear and pain
perception were highly significant in 4 studies (highly significant, p < 0.01)
and significant in 3 studies (p < 0.05); 5 studies had no significant results.
The studies were very heterogeneous. CONCLUSIONS: The results can improve the
understanding of the complexity of LBP perception and its therapy. The
generalization of the results is limited. To cover the correlation of
psychosocial and lifestyle factors and pain perception of LBP, further research
is required. To obtain a clearer picture of pain perception in persons with LBP,
standardized pain assessment would be beneficial. In addition, we recommend that
future studies follow standardized procedures to allow greater comparability.
PMID- 27501802
TI - Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic
Stroke.
AB - Dodecafluoropentane emulsion (DDFPe), an advanced oxygen transport drug, given IV
at 90-min intervals maintains viability in the penumbra during cerebral ischemia
in the standard rabbit anterior stroke model (STND). This study investigated
shortened dosage schedules of DDFPe in nonstandard posterior (NSTND) strokes
following occlusions of the posterior cerebral arteries. DDFPe given at shortened
schedules of 30 or 60-min injection intervals will reduce neurological deficits,
percent stroke volume (%SV), and serum glutamate levels in NSTND ischemic
strokes. New Zealand White rabbits (N = 26) were randomly placed into three
groups: A (n = 9) controls given saline injections every 60 min, B (n = 9) 2 %
DDFPe given IV every 30 min, and C (n = 8) DDFPe every 60 min. Injections began 1
h after embolization. Groups were subdivided into STND and NSTND based on
angiographically verified embolization of the cerebral arteries. Neurological
assessments and blood samples were done at 0.5-1-h intervals. Rabbits were
euthanized at 7 h following embolization. Stained brain slices were measured for
%SV. The 30 and 60-min subgroups did not differ and were combined as DDFPe-STND
or DDFPe-NSTND groups. In the DDFPe-STND stroke group, the %SV, neurological
assessment scores (NAS), and serum glutamate were decreased vs. STND controls (p
= 0.0016, 0.008, and 0.016, respectively). In the DDFPe-NSTND stroke group, %SV,
NAS, and serum glutamate did not differ statistically compared to NSTND controls
(p = 0.82, 0.097, and 0.06, respectively). More frequent dosage schedules
provided no additional improvement. In anterior strokes, DDFPe improves recovery
but not in the more severe NSTND strokes.
PMID- 27501803
TI - Gene Polymorphisms for Both Auto-antigen and Immune-Modulating Proteins Are
Associated with the Susceptibility of Autoimmune Myasthenia Gravis.
AB - Myasthenia gravis (MG) is an antibody-mediated autoimmune disease against
antigens at the neuromuscular junction. Both genetic and environmental factors
contribute to the susceptibility of MG. We undertook a case-control study to
explore the contribution of genes of the auto-antigen and immune-modulating
proteins in the pathogenesis of MG. We enrolled 389 adult MG patients and 487
healthy controls. Eighteen SNPs were selected from genes of cholinergic receptor
nicotinic alpha 1 (CHRNA1), autoimmune regulator (AIRE), cytotoxic T lymphocyte
associated protein 4 (CTLA-4), protein tyrosine phosphatase nonreceptor type 22
(PTPN22), and interleukin-10 (IL-10). Rs16862847 and rs2229957 in CHRNA1,
rs3761389 in AIRE, and rs733618 in CTLA-4 were significantly associated with MG,
with the highest association in SNPs of CHRNA1. Carrier of rs16862847 G allele
was found to be an independent risk factor in predicting high-level acetylcholine
receptor (AChR) antibodies (P = 0.003, OR = 10.296). Genetic interaction analysis
revealed a synergistic effect of CHRNA1 (rs16862847), AIRE (rs3761389), and CTLA
4 (rs733618) in the susceptibility of MG (P < 0.0001, OR = 1.95). These findings
highlight the role of auto-antigen gene (CHRNA1) in the autoimmune reactions
against AChR and reveal synergistic contribution of genes of both auto-antigen
and immune-regulating proteins (AIRE and CTLA-4) in the pathogenesis of MG.
PMID- 27501804
TI - Mitochondrion-Mediated Apoptosis Induced by Acrylamide is Regulated by a Balance
Between Nrf2 Antioxidant and MAPK Signaling Pathways in PC12 Cells.
AB - Acrylamide (ACR) is a potent toxin that affects the human nervous system.
However, the underlying mechanism of ACR neurotoxicity remains poorly understood.
In the present study, we investigated whether ACR induces mitochondrion-dependent
apoptosis and the involved signaling pathways in PC12 cells. ACR exposure
activated the mitochondrial apoptotic pathway in PC12 cells and triggered the up
regulation of Bax/Bcl-2 ratio, excessive release of cytochrome c, cleavage of
capase-9 and caspase-3, depolarization of the mitochondrial membrane, structural
damages to the mitochondria, and compaction of nuclear heterochromatin. ACR
induced oxidative stress was also observed based on distinct increase in cellular
reactive oxygen species (ROS) and malondialdehyde (MDA), and significant decrease
in glutathione (GSH). Mitogen-activated protein kinases (MAPK) signaling
including extracellular signal-regulated protein kinases (ERK), c-Jun N-terminal
kinases (JNK), and p38 were phosphorylated by ROS overproduction in PC12 cells in
a time-and dose-dependent manner. ACR promoted the translocation of nuclear
factor E2-related factor 2 (Nrf2) from the cytosol to the nucleus, thereby
enhancing the expression of downstream gamma-glutamyl-cysteine synthetase (gamma
GCS). The regulation of Nrf2 activation by MAPK pathways was confirmed by the
blockade of MAPK pathways. The suppression of JNK and p38 pathways showed a
protective effect on ACR-induced mitochondrial dysfunction and apoptosis. Nrf2
knockdown further enhanced MDA production and reduced GSH generation induced by
ACR. These results suggest that MAPK and Nrf2 signaling pathways contribute to
mitochondrion-mediated apoptosis induced by ACR in PC12 cells.
PMID- 27501805
TI - Distinct Hippocampal Expression Profiles of Long Non-coding RNAs in an
Alzheimer's Disease Model.
AB - Alzheimer's disease (AD), the most prevalent form of dementia worldwide, is a
complex neurodegenerative disease characterized by the progressive loss of memory
and other cognitive functions. The pathogenesis of AD is not yet completely
understood. Although long non-coding RNAs (lncRNAs) have recently been shown to
play a role in AD pathogenesis, the specific influences of lncRNAs in AD remain
largely unknown; in particular, hippocampal lncRNA expression profiles in AD rats
are lacking. In this study, microarray analysis was performed to investigate the
hippocampal expression patterns of dysregulated lncRNAs in a rat model of AD. A
total of 315 lncRNAs and 311 mRNAs were found to be significantly dysregulated in
the AD model (>=2.0 fold, p < 0.05). Then, quantitative real-time PCR was used to
validate the expression of selected lncRNAs and mRNAs. Bioinformatics tools and
databases were employed to explore the potential lncRNA functions. This is the
first study to comprehensively identify dysregulated hippocampal lncRNAs in AD
and to demonstrate the involvement of different lncRNA expression patterns in the
hippocampal pathogenesis of AD. This information will enable further research on
the pathogenesis of AD and facilitate the development of novel AD therapeutics
targeting lncRNAs.
PMID- 27501806
TI - Si/PEDOT:PSS Hybrid Solar Cells with Advanced Antireflection and Back Surface
Field Designs.
AB - Molybdenum oxide (MoO3) is one of most suitable antireflection (AR) layers for
silicon/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (Si/ PEDOT: PSS)
hybrid solar cells due to its well-matched refractive index (2.1). A simulation
model was employed to predict the optical characteristics of Si/ PEDOT: PSS
hybrid solar cells with the MoO3 layers as antireflection coatings (ARCs), as
well as to analyze the loss in current density. By adding an optimum thickness of
a 34-nm-thick ARC of MoO3 on the front side and an effective rear back surface
field (BSF) of phosphorus-diffused N (+) layer at the rear side, the hybrid cells
displayed higher light response in the visible and near infrared regions,
boosting a short-circuit current density (J sc) up to 28.7 mA/cm(2). The average
power conversion efficiency (PCE) of the Si/ PEDOT: PSS hybrid solar cells was
thus increased up to 11.90 %, greater than the value of 9.23 % for the reference
devices.
PMID- 27501807
TI - Teen Dating Violence, Sexual Harassment, and Bullying Among Middle School
Students: Examining Mediation and Moderated Mediation by Gender.
AB - This longitudinal study tested whether sexual harassment perpetration mediates
the relationship between bullying perpetration and teen dating violence (TDV)
perpetration and tested moderated mediation by assessing whether the
developmental pathway varies by gender among middle school-aged youth. Although
TDV has been associated with bullying and sexual harassment, the developmental
relationship among all three behaviors has rarely been examined, especially by
gender. The data were collected from one cohort of seventh grade middle school
students (N = 612) from four schools. Students were surveyed every 6 months
during seventh and eighth grades for a total of four waves of data collection.
Structural equation modeling (SEM) was conducted to address the study aims,
consisting of three stages: measurement models, mediation, and moderated
mediation (otherwise known as Contrast of Mediated Effects). Results indicate no
evidence of mediation. However, in the overall model, bullying and sexual
harassment both emerged as significant predictors of TDV at a later time point.
Among girls, only bullying significantly predicted TDV at a later time point,
and, among boys, only sexual harassment significantly predicted TDV at a later
time point. Prevention programs that target bullying and sexual harassment
perpetration may reduce later perpetration of TDV. Further research is needed to
disentangle the temporal relationships between these aggressive behaviors among
youth.
PMID- 27501808
TI - It's not just the big kids: both high and low BMI impact bracing success for
adolescent idiopathic scoliosis.
AB - PURPOSE: Bracing is a common treatment for patients with adolescent idiopathic
scoliosis (AIS) and is recommended for most skeletally immature patients with a
curve of 25-45 degrees in order to prevent or delay curve progression. The aim
of this study was to determine at which body habitus orthotic management for AIS
becomes less effective. We hypothesize that overweight children are more likely
to fail brace treatment. METHODS: This was a retrospective cohort study involving
consecutive patients with AIS treated with a thoracolumbosacral orthosis at a
large pediatric tertiary care center. Patients were divided into three groups
based on BMI: (1) high-BMI group (BMI >85th percentile); (2) low-BMI group (BMI
<20th percentile); (3) mid-BMI group (BMI 20th-85th percentile). Successful
orthotic treatment was defined as an increase in the primary curve of <5 degrees
, prevention of progression past 45 degrees , and avoidance of surgery. RESULTS:
The study cohort comprised 182 patients with a mean age of 12.5 years at brace
prescription and a mean follow-up of 2 years. Compared to the mid-BMI group, high
and low-BMI patients were significantly more likely to fail orthotic management.
The association between high-BMI and orthotic failure disappeared when compliance
and in-brace correction were taken into account, but the association between low
BMI and each poor outcome remained significant. CONCLUSIONS: Based on our
results, children on either end of the BMI spectrum are more likely to fail brace
treatment for scoliosis than their mid-BMI counterparts. In high-BMI patients,
this appears to be in large part attributable to an inadequacy of in-brace curve
correction as well as to poorer brace compliance, while a low BMI appears to be
an independent risk factor for brace failure.
PMID- 27501809
TI - Decreased PD-1 positive blood follicular helper T cells in patients with
psoriasis.
AB - Follicular helper T (Tfh) cells are recently characterized subset of helper T
cells, which are initially found in the germinal centers of B cell follicles. The
major role of Tfh cells is helping B cell activation and antibody production
during humoral immunity. Recently, blood Tfh cells were shown to be associated
with autoimmune diseases, such as systemic lupus erythematosus, rheumatoid
arthritis, bullous pemphigoid and psoriasis. There is only one study which
investigated Tfh cells in psoriasis patients. Therefore, in this study, we
evaluated and analyzed blood Tfh cells in Korean patients with psoriasis. A total
of 28 psoriasis patients and 16 healthy controls were enrolled. The frequency and
absolute number of CXCR5(+)PD-1(+) Tfh cells were decreased in patients with
psoriasis compared to healthy controls. CD4(+)CXCR5(+) T cells and
CXCR5(+)ICOS(+) Tfh cells did not show differences. The frequency and absolute
number of CXCR5(+)PD-1(+) Tfh cells in psoriasis patients negatively correlated
with erythrocyte sedimentation rate and positively correlated with disease
duration. The absolute number of CXCR5(+)ICOS(+) Tfh cells also showed positive
correlation with disease duration. However, the subpopulations of Tfh cells did
not correlate with Psoriasis Area and Severity Index. Serum interleukin-21 level
was significantly increased in psoriasis patients compared to healthy controls,
however, its level did not correlate with clinical and experimental parameters of
psoriasis patients. These findings suggest the decreased function of Tfh cells in
psoriasis, which could result in attenuated B cell immune responses in the
pathogenesis of psoriasis. However, further investigations are necessary to
confirm the function of Tfh cells in psoriasis vulgaris.
PMID- 27501810
TI - Ethnicity, Sex Work, and Incident HIV/STI Among Transgender Women in New York
City: A Three Year Prospective Study.
AB - In conjunction with a 3-year prospective study of 199 transgender women from the
New York City Area, we attempted to better understand why non-Whites are much
more likely than Whites to become HIV infected. We first assessed associations of
ethnicity with sex work, sexual risk behavior for HIV, and biologically
determined HIV/STI, and then assessed the extent to which these ethnic
differences are explained by socioeconomic factors, immigration status, and
sexual orientation. Statistical techniques included generalized estimating
equations and Cox proportional hazards. As expected, compared to Whites, Blacks
and Hispanics were more involved in the sex trade, more likely to report
unprotected receptive anal intercourse, and as a result, more likely to become
HIV/STI infected. All of these associations were mediated by androphilia, and to
a lesser extent androphilia/gynephilia. Sexual orientation is a significant but
little recognized factors associated with new cases of HIV/STI among transgender
women of color.
PMID- 27501812
TI - [Transcatheter aortic valve implantation and internal carotid artery stenting in
a 74-year-old female patient].
AB - This article presents the case of a combined intervention for transcatheter
aortic valve implantation (TAVI) and stenting of the internal carotid artery. Due
to severe aortic stenosis and a subacute infarction in the middle cerebral artery
territory, with neurological instability while hypotensive and cardiac failure
while hypertensive, it was decided to carry out the intervention as a single
combined procedure. An open surgical intervention was decided against because of
the high peri-interventional mortality risk. The intervention was complication
free but a slight subarachnoid hemorrhage occurred in the postinterventional
period. It was unclear if the bleeding was the result of cerebral hyperperfusion
poststenting, if bleeding in an ischemic region was favored by post-TAVI
hyperemia and whether the outcome would have been better with two separate
interventions.
PMID- 27501811
TI - Shifting the HIV Training and Research Paradigm to Address Disparities in HIV
Outcomes.
AB - Tailored programs to diversify the pool of HIV/AIDS investigators and provide
sufficient training and support for minority investigators to compete
successfully are uncommon in the US and abroad. This paper encourages a shift in
the HIV/AIDS training and research paradigm to effectively train and mentor
Latino researchers in the US, Latin America and the Caribbean. We suggest three
strategies to accomplish this: (1) coaching senior administrative and academic
staff of HIV/AIDS training programs on the needs, values, and experiences unique
to Latino investigators; (2) encouraging mentors to be receptive to a different
set of research questions and approaches that Latino researchers offer due to
their life experiences and perspectives; and (3) creating a virtual
infrastructure to share resources and tackle challenges faced by minority
researchers. Shifts in the research paradigm to include, retain, and promote
Latino HIV/AIDS researchers will benefit the scientific process and the patients
and communities who await the promise of HIV/AIDS research.
PMID- 27501815
TI - Latitudinal Gradients in Induced and Constitutive Resistance against Herbivores.
AB - Plants are hypothesized to evolve increased defense against herbivores at lower
latitudes, but an increasing number of studies report evidence that contradicts
this hypothesis. Few studies have examined the evolution of constitutive and
induced resistance along latitudinal gradients. When induction is not considered,
underlying patterns of latitudinal clines in resistance can be obscured because
plant resistance represents a combination of induced and constitutive resistance,
which may show contrasting patterns with latitude. Here, we asked if there are
latitudinal gradients in constitutive versus induced resistance by using
genotypes of Oenothera biennis (Onagraceae) sampled along an 18 degrees
latitudinal gradient. We conducted two bioassay experiments to compare the
resistance of plant genotypes against one generalist (Spodoptera exigua) and one
specialist (Acanthoscelidius acephalus) herbivore. These insects were assayed on:
i) undamaged control plants, ii) plants that had been induced with jasmonic acid,
and iii) plants induced with herbivore damage. Additionally, we examined
latitudinal gradients of constitutive and induced chemical resistance by
measuring the concentrations of total phenolics, the concentration of oxidized
phenolics, and the percentage of phenolics that were oxidized. Spodoptera exigua
showed lower performance on plants from lower latitudes, whereas A. acephalus
showed no latitudinal pattern. Constitutive total phenolics were greater in
plants from lower latitudes, but induced plants showed higher total phenolics at
higher latitudes. Oxidative activity was greatest at higher latitudes regardless
of induction. Overall, both latitude and induction have an impact on different
metrics of plant resistance to herbivory. Further studies should consider the
effect of induction and herbivore specialization more explicitly, which may help
to resolve the controversy in latitudinal gradients in herbivory and defense.
PMID- 27501814
TI - Sex and Aggregation-Sex Pheromones of Cerambycid Beetles: Basic Science and
Practical Applications.
AB - Research since 2004 has shown that the use of volatile attractants and pheromones
is widespread in the large beetle family Cerambycidae, with pheromones now
identified from more than 100 species, and likely pheromones for many more. The
pheromones identified to date from species in the subfamilies Cerambycinae,
Spondylidinae, and Lamiinae are all male-produced aggregation-sex pheromones that
attract both sexes, whereas all known examples for species in the subfamilies
Prioninae and Lepturinae are female-produced sex pheromones that attract only
males. Here, we summarize the chemistry of the known pheromones, and the optimal
methods for their collection, analysis, and synthesis. Attraction of cerambycids
to host plant volatiles, interactions between their pheromones and host plant
volatiles, and the implications of pheromone chemistry for invasion biology are
discussed. We also describe optimized traps, lures, and operational parameters
for practical applications of the pheromones in detection, sampling, and
management of cerambycids.
PMID- 27501816
TI - Iranian homograft heart valves: assessment of durability and late outcome.
AB - Durability and the rate of complications of homograft heart valves, adjusted for
patient-related contributors and surgical techniques, rely mainly on the quality
of allografts which in turn are mirrored in the donor characteristics and most
importantly recovery and processing procedures. Aimed to assess the quality, a
study was conducted to figure out the durability and late outcome following
homograft replacement with valved conduits procured by the Iranian Tissue Bank.
Retrospectively, the pre-implantation, perioperative and follow-up data of 400
non-consecutive recipients of cryopreserved heart valves (222 pulmonary and 178
aortic) from 2006 to 2015 were collected and analyzed in terms of variables
reflecting late outcome including adverse events and durability. In the context
of durability, the event of interest was defined as the need for homograft
replacement and homograft-related death. The mean follow-up time (SD) of study
entrants (male/female ratio, 1.4) was 49.8 (36.3) months. Median age at the time
of implantation was 11 years. Total 10-years mortality was 21 % (84/400),
including 66.7 % early (30-days mortality: 56/84) and 33.3 % late (28/84).
Overall late complication rate was 2 %. Median survival time was 120 months (95 %
CI 83.3-156.6). The pulmonary valves appeared to be more durable (P value <0.001)
and survival probabilities in small sized grafts were lower (P value 0.008). One
, five-, and ten-year graft survival was 82, 76 and 73 %, respectively. The
evidences suggest that the homografts function satisfactory with low rate of late
complications; nevertheless, more emphasis should be given to make long-term
durability comparable.
PMID- 27501813
TI - DNA Methylation and Urological Cancer, a Step Towards Personalized Medicine:
Current and Future Prospects.
AB - Urologic malignancies are some of the commonest tumors often curable when
diagnosed at early stage. However, accurate diagnostic markers and faithful
predictors of prognosis are needed to avoid over-diagnosis leading to
overtreatment. Many promising exploratory studies have identified epigenetic
markers in urinary malignancies based on DNA methylation, histone modification
and non-coding ribonucleic acid (ncRNA) expression that epigenetically regulate
gene expression. We review and discuss the current state of development and the
future potential of epigenetic biomarkers for more accurate and less invasive
detection of urological cancer, tumor recurrence and progression of disease
serving to establish diagnosis and monitor treatment efficacies. The specific
clinical implications of such methylation tests on therapeutic decisions and
patient outcome and current limitations are also discussed.
PMID- 27501818
TI - The Central Nervous System and Bone Metabolism: An Evolving Story.
AB - Our understanding of the control of skeletal metabolism has undergone a dynamic
shift in the last two decades, primarily driven by our understanding of energy
metabolism. Evidence demonstrating that leptin not only influences bone cells
directly, but that it also plays a pivotal role in controlling bone mass
centrally, opened up an investigative process that has changed the way in which
skeletal metabolism is now perceived. Other central regulators of bone metabolism
have since been identified including neuropeptide Y (NPY), serotonin,
endocannabinoids, cocaine- and amphetamine-regulated transcript (CART),
adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast
differentiation, proliferation and function. The sympathetic nervous system was
originally identified as the predominant efferent pathway mediating central
signalling to control skeleton metabolism, in part regulated through circadian
genes. More recent evidence points to a role of the parasympathetic nervous
system in the control of skeletal metabolism either through muscarinic influence
of sympathetic nerves in the brain or directly via nicotinic receptors on
osteoclasts, thus providing evidence for broader autonomic skeletal regulation.
Sensory innervation of bone has also received focus again widening our
understanding of the complex neuronal regulation of bone mass. Whilst scientific
advance in this field of bone metabolism has been rapid, progress is still
required to understand how these model systems work in relation to the multiple
confounders influencing skeletal metabolism, and the relative balance in these
neuronal systems required for skeletal growth and development in childhood and
maintaining skeletal integrity in adulthood.
PMID- 27501817
TI - Laser-Sintered Constructs with Bio-inspired Porosity and Surface Micro/Nano
Roughness Enhance Mesenchymal Stem Cell Differentiation and Matrix Mineralization
In Vitro.
AB - Direct metal laser sintering can produce porous Ti-6Al-4V orthopedic and dental
implants. The process requires reduced resources and time and can provide greater
structural control than machine manufacturing. Implants in bone are colonized by
mesenchymal stem cells (MSCs), which can differentiate into osteoblasts and
contribute to osseointegration. This study examined osteoblast differentiation
and matrix mineralization of human MSCs cultured on laser-sintered Ti-6Al-4V
constructs with varying porosity and at different time scales. 2D solid disks and
low, medium and high porosity (LP, MP, and HP) 3D constructs based on a human
trabecular bone template were laser sintered from Ti-6Al-4V powder and further
processed to have micro- and nanoscale roughness. hMSCs exhibited greater
osteoblastic differentiation and local factor production on all 3D porous
constructs compared to 2D surfaces, which was sustained for 9 days without use of
exogenous factors. hMSCs cultured for 8 weeks on MP constructs in osteogenic
medium (OM), OM supplemented with BMP2 or collagen-coated MP constructs in OM
exhibited bone-like extracellular matrix mineralization. Use of bio-inspired
porosity for the 3D architecture of additively manufactured Ti-6Al-4V enhanced
osteogenic differentiation of hMSCs beyond surface roughness alone. This study
suggests that a 3D architecture may enhance the osseointegration of orthopedic
and dental implants in vivo.
PMID- 27501819
TI - The Role of Tumor Necrosis Factor Alpha and TNF Superfamily Members in Bone
Damage in Patients with End-Stage Chronic Obstructive Lung Disease Prior to Lung
Transplantation.
AB - A disequilibrium of tumor necrosis superfamily (TNF) members, including the serum
osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand,
soluble TNF-related apoptosis-inducing ligand and TNF-alpha, was associated with
the occurrence of a reduced skeletal mass and osteoporosis in male patients with
end-stage chronic obstructive pulmonary disease (COPD). The purpose of this study
was to explore the associations between serum biomarkers of tumor necrosis factor
(TNF) superfamily and body and bone compositions in end-stage COPD males.
Pulmonary function, T-score at the lumbar spine and femoral neck, lean mass,
serum osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappaB
ligand (sRANKL), TNF-alpha and its receptors (sTNFR-I, sTNFR-II) and soluble TNF
related apoptosis-inducing ligand (sTRAIL) levels were evaluated in 48 male
patients with end-stage COPD and 36 healthy male volunteers. OPG was lower in
male COPD patients than in control subjects, whereas sRANKL, TNF-alpha and its
receptors were higher. The serum sTRAIL level showed a tendency to increase
compared with that of healthy subjects (P = 0.062). Serum OPG showed a positive
correlation with bone density. In contrast, serum TNF-alpha, sRANKL and sTRAIL
were inversely associated with pretransplant bone density. We have noted the
appearance of statistically significant inverse relationships between lean mass
values and TNF-alpha, sTNFR-I and II and sRANKL levels in male COPD patients.
Moreover, there was a negative correlation between sTRAIL levels with airway
obstruction (P = 0.005) and hypercapnia (P = 0.042) in advanced COPD patients.
Through a multiple linear regression analysis, our study revealed that a
disequilibrium of TNF family members was strongly associated with the occurrence
of a reduced skeletal mass and osteoporosis. These results provide further
evidence that abnormal levels of TNF superfamily molecules may cause not only a
decrease in BMD, but also lower muscle mass in end-stage COPD.
PMID- 27501820
TI - The association of parental education with childhood undernutrition in low- and
middle-income countries: comparing the role of paternal and maternal education.
AB - Background: Most existing research on the association of parental education with
childhood undernutrition focuses on maternal education and often ignores paternal
education. We systematically investigate differences in maternal and paternal
education and their association with childhood undernutrition. Methods: One
hundred and eighty Demographic and Health Surveys from 62 countries performed
between 1990 and 2014 were analysed. We used linear-probability models to predict
childhood undernutrition prevalences, measured as stunting, underweight and
wasting, for all combinations of maternal and paternal attainment in school.
Models were adjusted for demographic and socio-economic covariates for the child,
mother and household, country-level fixed effects and clustering. Additional
specifications adjust for local area characteristics instead of country fixed
effects. Results: Both higher maternal and paternal education levels are
associated with lower childhood undernutrition. In regressions adjusted for child
age and sex as well as country-level fixed effects, the association is stronger
for maternal education than for paternal education when their combined level of
education is held constant. In the fully adjusted models, the observed
differences in predicted undernutrition prevalences are strongly attenuated,
suggesting a similar importance of maternal and paternal education. These
findings are confirmed by the analysis of composite schooling indicators.
Conclusions: We find that paternal education is similarly important for reducing
childhood undernutrition as maternal education and should therefore receive
increased attention in the literature.
PMID- 27501821
TI - Transfemoral transcatheter aortic-valve replacement should be preferred over
surgery in most intermediate-risk patients.
PMID- 27501822
TI - Controlling the half-metallicity of Heusler/Si(1 1 1) interfaces by a monolayer
of Si-Co-Si.
AB - By using first-principles calculations we show that the spin-polarization
reverses its sign at atomically abrupt interfaces between the half-metallic
Co2(Fe,Mn)(Al,Si) and Si(1 1 1). This unfavourable spin-electronic configuration
at the Fermi-level can be completely removed by introducing a Si-Co-Si monolayer
at the interface. In addition, this interfacial monolayer shifts the Fermi-level
from the valence band edge close to the conduction band edge of Si. We show that
such a layer is energetically favourable to exist at the interface. This was
further confirmed by direct observations of CoSi2 nano-islands at the interface,
by employing atomic resolution scanning transmission electron microscopy.
PMID- 27501823
TI - The dietary effect of milk sphingomyelin on the lipid metabolism of
obese/diabetic KK-A(y) mice and wild-type C57BL/6J mice.
AB - Purified milk sphingomyelin (SM) was obtained from lipid concentrated butter
serum (LC-BS) by successive separations involving solvent fractionation,
selective saponification, and silicic acid column chromatography. The SM obtained
was given to obese/diabetic KK-A(y) mice and wild-type C57BL/6J mice. SM
supplementation significantly increased fecal lipids paralleled with a decrease
in non-HDL cholesterol levels in the serum and neutral lipids and in cholesterol
levels in the livers of KK-A(y) mice. The reduction of liver lipid levels also
resulted in a decrease in the total fatty acid content of the KK-A(y) mice
livers, while n-3 fatty acids derived from the conversion of alpha-linolenic acid
(18:3n-3) increased due to SM supplementation. In contrast to the KK-A(y) mice,
little change in the serum and liver lipids was observed in wild-type C57BL/6J
mice. The present study suggests that SM may be effective only in subjects with
metabolic disorders.
PMID- 27501824
TI - A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines.
AB - A metal-free hydrogenation of 3-substituted 2H-1,4-benzoxazines has been
successfully realized with 2.5 mol% of B(C6F5)3 as a catalyst to furnish a
variety of 3,4-dihydro-2H-1,4-benzoxazines in 93-99% yields. Up to 42% ee was
also achieved for the asymmetric hydrogenation with the use of a chiral diene and
HB(C6F5)2.
PMID- 27501826
TI - Organizing Exposure Data Is Beyond Conceptualization.
PMID- 27501825
TI - Analyte-directed formation of emissive excimers for the selective detection of
polyamines.
AB - A convenient and selective method for the sensing of polyamines, which are
important biomarkers for cancers, has been developed. The fluorescence light-up
mechanism utilizes the analyte-induced formation of emissive excimers of a
sulfonated probe. Detection is achieved in aqueous media and artificial urine
samples, as indicated by an excellent fluorescence turn-on signal with a large
spectral shift.
PMID- 27501827
TI - Foldable Thermoelectric Materials: Improvement of the Thermoelectric Performance
of Directly Spun CNT Webs by Individual Control of Electrical and Thermal
Conductivity.
AB - We suggest the fabrication of foldable thermoelectric (TE) materials by embedding
conducting polymers into Au-doped CNT webs. The CNT bundles, which are
interconnected by a direct spinning method to form 3D networks without
interfacial contact resistance, provide both high electrical conductivity and
high carrier mobility. The ZT value of the spun CNT web is significantly enhanced
through two simple processes. Decorating the porous CNT webs with Au
nanoparticles increases the electrical conductivity, resulting in an optimal ZT
of 0.163, which represents a more than 2-fold improvement compared to the ZT of
pristine CNT webs (0.079). After decoration, polyaniline (PANI) is integrated
into the Au-doped CNT webs both to improve the Seebeck coefficient by an energy
filtering effect and to decrease the thermal conductivity by the phonon
scattering effect. This leads to a ZT of 0.203, which is one of the highest ZT
values reported for organic TE materials. Moreover, Au-doped CNT/PANI web is
ultralightweight, free-standing, thermally stable, and mechanically robust, which
makes it a viable candidate for a hybrid TE conversion device for wearable
electronics. When a 20 K temperature gradient is applied to the TE module
consisting of seven p-n couples, 1.74 MUW of power is generated.
PMID- 27501828
TI - An overview of the bacterial contribution to Crohn disease pathogenesis.
AB - Crohn disease (CD) is a chronic inflammatory condition primarily affecting the
gastro-intestinal tract and is characterized by reduced bacterial diversity. The
exact cause of disease is unknown; however, evidence suggests that several
components, including microbiota, may contribute to the underlying pathology and
disease development. Perturbation of the host-microbe commensal relationship is
considered the main driving force of tissue destruction and pathological changes
seen in CD. Several putative bacterial pathogens including species from
Mycobacterium, Campylobacter and Helicobacter are postulated in the aetiology of
CD. However, to date, no strong evidence supports a single bacterium contributing
overall to CD pathogenesis. Alternatively, dysbiosis or bacterial imbalance is
more widely accepted as a leading factor in the disrupted host-immune system
cross-talk resulting in subsequent intestinal inflammation. Depletion of symbiont
microbes including Firmicutes, Bifidobacterium and Clostridia, in conjunction
with an increase in pathobiont microbes from Bacteroidetes and Enterobacteria, is
a striking feature observed in CD. No single factor has been identified as
driving this dysbiosis, although diet, antibiotic exposure and possible early
life events in presence of underlying genetic susceptibility may contribute. The
aim of this review is to highlight the current accumulating literature on the
proposed role of bacteria in the pathogenesis of CD.
PMID- 27501829
TI - Understanding the pathophysiology of the human TB lung granuloma using in vitro
granuloma models.
AB - Tuberculosis remains a major human health threat that infects one in three
individuals worldwide. Infection with Mycobacterium tuberculosis is a standoff
between host and bacteria in the formation of a granuloma. This review will
introduce a variety of bacterial and host factors that impact individual
granuloma fates. The authors describe advances in the development of in vitro
granuloma models, current evidence surrounding infection and granuloma
development, and the applicability of existing in vitro models in the study of
human disease. In vitro models of infection help improve our understanding of
pathophysiology and allow for the discovery of other potential models of study.
PMID- 27501830
TI - CXCR4 Overexpression in Human Adipose Tissue-Derived Stem Cells Improves Homing
and Engraftment in an Animal Limb Ischemia Model.
AB - We investigated the effects of transplantation of CXCR4-overexpressing adipose
tissue-derived stem cells (ADSCs) into a mouse diabetic hindlimb ischemia model
on homing and engraftment as early as 48 h after transplant. CXCR4-overexpressing
ADSCs were intramuscularly or intravenously injected into diabetic mice with
hindlimb ischemia. After 48 h, muscle tissues in the femur and tibia were
collected, and the CXCR4 expression pattern was analyzed by immunofluorescence
staining. The homing and engraftment of transplanted CXCR4-overexpressing ADSCs
into the ischemic area were significantly increased, and intravenous (systemic)
injection resulted in the more effective delivery of stem cells to the target
site 48 h posttransplantation. Furthermore, CXCR4-overexpressing ADSCs more
efficiently contributed to long-term engraftment and muscle tissue regeneration
than normal ADSCs in a limb ischemia model. In addition, the homing and
engraftment of ADSCs were correlated with the CXCR4 transfection efficiency.
These results demonstrated that enhanced CXCR4 signaling could significantly
improve the early homing and engraftment of ADSCs into ischemic areas as well as
the long-term engraftment and ultimate muscle tissue regeneration.
PMID- 27501831
TI - TREM2 p.H157Y Variant and the Risk of Alzheimer's Disease: A Meta-Analysis
Involving 14,510 Subjects.
AB - We recently revealed that p.H157Y (rs2234255), a rare coding variant of
triggering receptor expressed on myeloid cells 2 gene (TREM2), was associated
with Alzheimer's disease (AD) susceptibility in Han Chinese. Contrastingly,
although p.H157Y was previously identified in both AD cases and controls by
several sequencing studies, no association of this variant with disease
susceptibility was reported. To gain a credible conclusion on the association
between p.H157Y and AD risk, a meta-analysis involving 7,102 cases and 7,408
controls was conducted. Our results indicated that p.H157Y was associated with an
increased risk of AD (OR=3.65, 95% CI: 1.61-8.28; P=0.002), further establishing
TREM2 as an important susceptibility gene for this disease.
PMID- 27501832
TI - Mesenchymal Stem Cell Secretome: A Potential Tool for the Prevention of Muscle
Degenerative Changes Associated With Chronic Rotator Cuff Tears.
AB - BACKGROUND: Massive rotator cuff tears (MRCTs) are usually chronic lesions with
pronounced degenerative changes, where advanced fatty degeneration and atrophy
can make the tear irreparable. Human mesenchymal stem cells (hMSCs) secrete a
range of growth factors and vesicular systems, known as secretome, that mediates
regenerative processes in tissues undergoing degeneration. PURPOSE: To study the
effect of hMSC secretome on muscular degenerative changes and shoulder function
on a rat MRCT model. STUDY DESIGN: Controlled laboratory study. METHODS: A
bilateral 2-tendon (supraspinatus and infraspinatus) section was performed to
create an MRCT in a rat model. Forty-four Wistar-Han rats were randomly assigned
to 6 groups: control group (sham surgery), lesion control group (MRCT), and 4
treated-lesion groups according to the site and periodicity of hMSC secretome
injection: single local injection, multiple local injections, single systemic
injection, and multiple systemic injections. Forelimb function was analyzed with
the staircase test. Atrophy and fatty degeneration of the muscle were evaluated
at 8 and 16 weeks after injury. A proteomic analysis was conducted to identify
the molecules present in the hMSC secretome that can be associated with muscular
degeneration prevention. RESULTS: When untreated for 8 weeks, the MRCT rats
exhibited a significantly higher fat content (0.73% +/- 0.19%) compared with rats
treated with a single local injection (0.21% +/- 0.04%; P < .01) or multiple
systemic injections (0.25% +/- 0.10%; P < .05) of hMSC secretome. At 16 weeks
after injury, a protective effect of the secretome in the multiple systemic
injections (0.62% +/- 0.14%; P < .001), single local injection (0.76% +/- 0.17%;
P < .001), and multiple local injections (1.35% +/- 0.21%; P < .05) was observed
when compared with the untreated MRCT group (2.51% +/- 0.42%). Regarding muscle
atrophy, 8 weeks after injury, only the single local injection group (0.0993% +/-
0.0036%) presented a significantly higher muscle mass than that of the untreated
MRCT group (0.0794% +/- 0.0047%; P < .05). Finally, the proteomic analysis
revealed the presence of important proteins with muscle regeneration, namely,
pigment epithelium-derived factor and follistatin. CONCLUSION: The study data
suggest that hMSC secretome effectively decreases the fatty degeneration and
atrophy of the rotator cuff muscles. CLINICAL RELEVANCE: We describe a new
approach for decreasing the characteristic muscle degeneration associated with
chronic rotator cuff tears. This strategy is particularly important for patients
whose tendon healing after later surgical repair could be compromised by the
progressing degenerative changes. In addition, both precise intramuscular local
injection and multiple systemic secretome injections have been shown to be
promising delivery forms for preventing muscle degeneration.
PMID- 27501833
TI - Influence of the Heel-to-Toe Drop of Standard Cushioned Running Shoes on Injury
Risk in Leisure-Time Runners: A Randomized Controlled Trial With 6-Month Follow
up.
AB - BACKGROUND: Modern running shoes are available in a wide range of heel-to-toe
drops (ie, the height difference between the forward and rear parts of the inside
of the shoe). While shoe drop has been shown to influence strike pattern, its
effect on injury risk has never been investigated. Therefore, the reasons for
such variety in this parameter are unclear. PURPOSE: The first aim of this study
was to determine whether the drop of standard cushioned running shoes influences
running injury risk. The secondary aim was to investigate whether recent running
regularity modifies the relationship between shoe drop and injury risk. STUDY
DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Leisure-time
runners (N = 553) were observed for 6 months after having received a pair of
shoes with a heel-to-toe drop of 10 mm (D10), 6 mm (D6), or 0 mm (D0). All
participants reported their running activities and injuries (time-loss
definition, at least 1 day) in an electronic system. Cox regression analyses were
used to compare injury risk between the 3 groups based on hazard rate ratios
(HRs) and their 95% CIs. A stratified analysis was conducted to evaluate the
effect of shoe drop in occasional runners (<6 months of weekly practice over the
previous 12 months) versus regular runners (>=6 months). RESULTS: The overall
injury risk was not different among the participants who had received the D6 (HR,
1.30; 95% CI, 0.86-1.98) or D0 (HR, 1.17; 95% CI, 0.76-1.80) versions compared
with the D10 shoes. After stratification according to running regularity, low
drop shoes (D6 and D0) were found to be associated with a lower injury risk in
occasional runners (HR, 0.48; 95% CI, 0.23-0.98), whereas these shoes were
associated with a higher injury risk in regular runners (HR, 1.67; 95% CI, 1.07
2.62). CONCLUSION: Overall, injury risk was not modified by the drop of standard
cushioned running shoes. However, low-drop shoes could be more hazardous for
regular runners, while these shoes seem to be preferable for occasional runners
to limit injury risk.
PMID- 27501834
TI - The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves
the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries.
AB - BACKGROUND: Although muscle injuries tend to heal uneventfully in most cases,
incomplete functional recovery commonly occurs as a result of scar tissue
formation at the site of injury, even after treatment with muscle-derived stem
cells (MDSCs). HYPOTHESIS: The transplantation of MDSCs in the presence of a
transforming growth factor beta1 (TGF-beta1) antagonist (losartan) would result
in decreased scar tissue formation and enhance muscle regeneration after
contusion injuries in a mouse model. STUDY DESIGN: Controlled laboratory study.
METHODS: An animal model of muscle contusion was developed using the tibialis
anterior muscle in 48 healthy mice at 8 to 10 weeks of age. After sustaining
muscle contusion injuries, the mice were divided into 4 groups: (1) saline
injection group (control group; n = 15), (2) MDSC transplantation group (MDSC
group; n = 15), (3) MDSC transplantation plus oral losartan group (MDSC/losartan
group; n = 15), and (4) healthy uninjured group (healthy group; n = 3). Losartan
was administrated systemically beginning 3 days after injury and continued until
the designated endpoint (1, 2, or 4 weeks after injury). MDSCs were transplanted
4 days after injury. Muscle regeneration and fibrotic scar formation were
evaluated by histology, and the expression of follistatin, MyoD, Smad7, and
Smad2/3 were analyzed by immunohistochemistry and reverse transcription
polymerase chain reaction analysis. Functional recovery was measured via
electrical stimulation of the peroneal nerve. RESULTS: When compared with MDSC
transplantation alone, MDSC/losartan treatment resulted in significantly
decreased scar formation, an increase in the number of regenerating myofibers,
and improved functional recovery after muscle contusions. In support of these
findings, the expression levels of Smad7 and MyoD were significantly increased in
the group treated with both MDSCs and losartan. CONCLUSION: When compared with
MDSCs alone, the simultaneous treatment of muscle contusions with MDSCs and
losartan significantly reduced scar formation, increased the number of
regenerating myofibers, and improved the functional recovery of muscle; these
effects were caused, at least in part, by the losartan-mediated upregulation of
Smad7 and MyoD. Increased levels of Smad7 and MyoD together reduced the
deposition of scar tissue (via the inhibition of TGF-beta1 by Smad7) and
committed the transplanted MDSCs toward a myogenic lineage (via Smad7-regulated
MyoD expression). CLINICAL RELEVANCE: The study findings contribute to the
development of biological treatments to accelerate and improve the quality of
muscle healing after injury.
PMID- 27501835
TI - Arthroscopic Bankart Repair Versus Open Bristow-Latarjet for Shoulder
Instability: A Matched-Pair Multicenter Study Focused on Return to Sport.
AB - BACKGROUND: The arthroscopic Bankart repair and open Bristow-Latarjet procedure
are the 2 most commonly used techniques to treat recurrent shoulder instability.
PURPOSE: To compare in a case control-matched manner the 2 techniques, with
particular emphasis on return to sport after surgery. STUDY DESIGN: Cohort study;
Level of evidence, 3. METHODS: A study was conducted in 2 hospitals matching 60
patients with posttraumatic recurrent anterior shoulder instability with a
minimum follow-up of 2 years (30 patients treated with arthroscopic Bankart
procedure and 30 treated with open Bristow-Latarjet procedure). Patients with
severe glenoid bone loss and revision surgeries were excluded. In one hospital,
patients were treated with arthroscopic Bankart repair using anchors; in the
other, patients underwent the Bristow-Latarjet procedure. Patients were matched
according to age at surgery, type and level of sport practiced before shoulder
instability (Degree of Shoulder Involvement in Sports [DOSIS] scale), and number
of dislocations. The primary outcomes were return to sport (Subjective Patient
Outcome for Return to Sports [SPORTS] score), rate of recurrent instability,
Oxford Shoulder Instability Score (OSIS), Subjective Shoulder Value (SSV),
Western Ontario Shoulder Instability Index (WOSI), and range of motion (ROM).
RESULTS: After a mean follow-up of 5.3 years (range, 2-9 years), patients who
underwent arthroscopic Bankart repair obtained better results in terms of return
to sport (SPORTS score: 8 vs 6; P = .02) and ROM in the throwing position (86
degrees vs 79 degrees ; P = .01), and they reported better subjective perception
of the shoulder (SSV: 86% vs 75%; P = .02). No differences were detectable using
the OSIS or WOSI. The rate of recurrent instability was not statistically
different between the 2 groups (Bankart repair 10% vs Bristow-Latarjet 0%; P =
.25), although the study may have been underpowered to detect a clinically
important difference in this parameter. The multiple regression analysis showed
that the independent variables associated with return to sport were preoperative
DOSIS scale, type of surgery, and recurrent dislocations after surgery. Patients
who played sports with high upper extremity involvement (eg, swimming, rugby,
martial arts) at a competitive level (DOSIS scale 9 or 10) had a lower level of
return to sport with both repair techniques. CONCLUSION: Arthroscopic
stabilization using anchors provided better return to sport and subjective
perception of the shoulder compared with the open Bristow-Latarjet procedure in
the population studied. Recurrence may be higher in the arthroscopic Bankart
group; further study is needed on this point.
PMID- 27501836
TI - Lower Limb Length Discrepancy After High Tibial Osteotomy: Prospective Randomized
Controlled Trial of Lateral Closing Versus Medial Opening Wedge Osteotomy.
AB - BACKGROUND: High tibial osteotomy (HTO) produces valgus limb alignment, and this
change can affect lower limb length. PURPOSE: To compare the change in lower limb
length and the discrepancy compared with the contralateral limb after unilateral
lateral closing wedge HTO (CWHTO) and medial opening wedge HTO (OWHTO). STUDY
DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: In this
study, 30 knees undergoing unilateral CWHTO and 30 knees undergoing unilateral
OWHTO for medial compartmental osteoarthritis were analyzed with 1-year follow
up. The tibial length, lower limb length, and lower limb length discrepancy were
measured preoperatively and 1 year postoperatively. The patients' subjective
sensation of, and discomfort due to, the lower limb length discrepancy were
recorded 1 year postoperatively. Univariate and multivariate linear regression
analyses were conducted to identify predictors related to the change in lower
limb length. RESULTS: The mean lengths of the tibia and lower limb increased
significantly after OWHTO (5.2 +/- 3.7 and 7.6 +/- 2.1 mm, respectively; P <
.001). The mean tibial length decreased significantly after CWHTO (-6.0 +/- 2.1
mm; P < .001); however, the mean lower limb length change was not significant (
0.8 +/- 2.5 mm; P = .073). The mean lower limb length discrepancy increased
significantly after OWHTO (-0.5 +/- 0.7 to 7.2 +/- 2.1 mm; P < .001) but not
after CWHTO (-0.7 +/- 0.6 to -1.0 +/- 2.5 mm; P = .539). A significantly greater
proportion of patients in the OWHTO group were aware of (70% vs 20%,
respectively; P = .002), and uncomfortable because of (37% vs 7%, respectively; P
= .010), the lower limb length discrepancy compared with those in the CWHTO
group. The strongest predictor of a change in lower limb length was the wedge
length in the OWHTO group and the preoperative hip-knee-ankle angle in the CWHTO
group. CONCLUSION: The lower limb length change and discrepancy were significant
after unilateral OWHTO, whereas they were negligible after unilateral CWHTO.
CWHTO was more beneficial in cases of unilateral HTO to minimize the discrepancy
of lower limb length rather than OWHTO, particularly in knees requiring a large
correction. REGISTRATION: Clinical Trials Registry Platform (protocol number
KCT00001684).
PMID- 27501837
TI - Factors responsible for poor sleep quality in patients with chronic obstructive
pulmonary disease.
AB - BACKGROUND: Sleep disturbance is a common complaint in patients with chronic
obstructive lung disease (COPD). However, the factors resulting in sleep
disturbance remain unclear. This retrospective, observational, multicenter study
aimed to identify the factors associated with sleep disturbance in patients with
COPD. METHODS: The study was a retrospective, observational, and multicenter
research. Data including age, sex, body mass index, smoking status, COPD inhaler
prescribed, clinical symptoms, pulmonary function tests, medical history of
comorbidities, and questionnaires were collected. Parameters including
demographics, symptoms, medication, severity, functional classification, and
comorbidities were correlated with sleep quality scores. RESULTS: Among 377
patients with COPD, 200 (53 %) patients experienced poor sleep quality (Pittsburg
Sleep Quality Index scores > 5). A significant difference in sleep quality, as
measured by PSQI scores, was noted between groups based on the 2011 Global
Initiatives for Chronic Obstructive Lung Disease (GOLD) classification system.
The most common sleep disturbances included "getting up to use the bathroom"
(70.3 %), "wake up at night or early morning" (40.3 %), and "cough and snore
loudly at night" (15.9 %). The use of inhaled corticosteroids, the presence of
wheezing, COPD Assessment Test (CAT) scores, and Modified Medical Research
Council (mMRC) dyspnea scale scores positively correlated with poor sleep quality
(odds ratio: 1.51, 1.66, 1.09, and 1.30, respectively). Upon multivariate
analysis, the CAT score was an independent factor for poor sleep quality in these
patients. With the exception of sleep problem items, based on the CAT
questionnaire, phlegm was significantly higher in COPD patients with poor sleep
quality. CONCLUSIONS: Poor sleep quality is common among patients with COPD and
symptoms including wheeze, phlegm, and inhaled corticosteroid use may contribute
to poor sleep quality. The CAT score is a good indicator of poor sleep quality in
patients with COPD.
PMID- 27501838
TI - Transcriptome profiling of drought responsive noncoding RNAs and their target
genes in rice.
AB - BACKGROUND: Plant transcriptome profiling has provided a tool for understanding
the mechanisms by which plants respond to stress conditions. Analysis of genome
wide transcriptome will provides a useful dataset of drought responsive noncoding
RNAs and their candidate target genes that may be involved in drought stress
responses. RESULTS: Here RNA-seq analyses of leaves from drought stressed rice
plants was performed, producing differential expression profiles of noncoding
RNAs. We found that the transcript levels of 66 miRNAs changed significantly in
response to drought conditions and that they were negatively correlated with
putative target genes during the treatments. The negative correlations were
further validated by qRT-PCR using total RNAs from both drought-treated leaves
and various tissues at different developmental stages. The drought responsive
miRNA/target pairs were confirmed by the presence of decay intermediates
generated by miRNA-guided cleavages in Parallel Analysis of RNA Ends (PARE)
libraries. We observed that the precursor miR171f produced two different mature
miRNAs, miR171f-5p and miR171f-3p with 4 candidate target genes, the former of
which was responsive to drought conditions. We found that the expression levels
of the miR171f precursor negatively correlated with those of one candidate target
gene, but not with the others, suggesting that miR171f-5p was drought-responsive,
with Os03g0828701-00 being a likely target. Pre-miRNA expression profiling
indicated that miR171f is involved in the progression of rice root development
and growth, as well as the response to drought stress. Ninety-eight lncRNAs were
also identified, together with their corresponding antisense transcripts, some of
which were responsive to drought conditions. CONCLUSIONS: We identified rice
noncoding RNAs (66 miRNAs and 98 lncRNAs), whose expression was highly regulated
by drought stress conditions, and whose transcript levels negatively correlated
with putative target genes.
PMID- 27501839
TI - Healthcare Outbreaks Associated With Dental Unit Water Systems: Strong Scientific
Evidence of Minimal Risk.
PMID- 27501840
TI - Reply to Petti.
PMID- 27501841
TI - The Spectrum of Serious Infections Among Patients Receiving Immune Checkpoint
Blockade for the Treatment of Melanoma.
AB - The risk of infection among patients receiving immune checkpoint blockade is
unknown. We retrospectively reviewed medical records of 740 patients with
melanoma who received immune checkpoint blockers. Serious infection occurred in
54 patients (7.3%). The main risk factors were receipt of corticosteroids and/or
infliximab.
PMID- 27501843
TI - Hospitalizations in Immigrants and Nonimmigrants Diagnosed With Chronic Hepatitis
C Infection in Quebec.
AB - BACKGROUND: Rates of hospitalization due to chronic hepatitis C virus (HCV) are
increasing in Canada and the United States. A large proportion of immigrants
originate from countries with intermediate to high HCV prevalence but are not
screened for HCV post-arrival and may therefore have increased risks of liver
related complications and hospitalization. METHODS: We conducted a retrospective
cohort study of reported HCV cases in Quebec, Canada, from 1998 to 2007 that were
linked to administrative health databases. Outcomes included all-cause and liver
related hospitalizations and in-hospital days in immigrants compared with
nonimmigrants adjusted for age, sex, and comorbidities. RESULTS: We identified
20 139 HCV cases; 9% (N = 1821) were immigrants. At diagnosis, immigrants were
older (47.6 vs 43.2 years) and more likely to have hepatocellular carcinoma (HCC;
0.93% vs 0.31%), while nonimmigrants were 2- to 10-fold more likely to have
substance use-related comorbidities. Mean time to HCV diagnosis after arrival was
9.8 years. Nonimmigrants had higher rates of all-cause hospitalization (adjusted
rate ratio [95% confidence interval], 1.42 [1.35-1.47]), driven by mental illness
and injury and/or poisoning. Unadjusted liver-related hospitalization rates were
similar between cohorts. After adjustment, immigrant status was associated with
lower rates of liver-related hospitalization (0.68 [.53-.88]). CONCLUSIONS:
Higher burden of all-cause hospitalization in nonimmigrants likely reflects more
prevalent behavioral comorbidities. Similar liver-related hospitalization rates
appear to be driven by older age in immigrants who were more likely to have HCC
at diagnosis possibly reflecting delayed HCV diagnosis. These findings suggest
that earlier screening and treatment in immigrants could play an important role
in preventing HCV complications in this population.
PMID- 27501844
TI - Macracanthorhynchus ingens Infection in an 18-Month-Old Child in Florida: A Case
Report and Review of Acanthocephaliasis in Humans.
AB - A case of acanthocephaliasis in an 18-month-old child caused by
Macracanthorhynchus ingens is reported from Florida. This represents only the
third documented case of this species in a human host. An overview of human cases
of acanthocephaliasis in the literature is presented, along with a review of the
biology, clinical manifestations and pathology in the human host, morphology, and
diagnosis.
PMID- 27501845
TI - The Epigenetic Regulator HDAC1 Modulates Transcription of a Core Cardiogenic
Program in Human Cardiac Mesenchymal Stromal Cells Through a p53-Dependent
Mechanism.
AB - Histone deacetylase (HDAC) regulation is an essential process in myogenic
differentiation. Inhibitors targeting the activity of specific HDAC family
members have been shown to enhance the cardiogenic differentiation capacity of
discrete progenitor cell types; a key property of donor cell populations
contributing to their afforded benefits in cardiac cell therapy applications. The
influence of HDAC inhibition on cardiac-derived mesenchymal stromal cell (CMC)
transdifferentiation or the role of specific HDAC family members in dictating
cardiovascular cell lineage specification has not been investigated. In the
current study, the consequences of HDAC inhibition on patient-derived CMC
proliferation, cardiogenic program activation, and cardiovascular
differentiation/cell lineage specification were investigated using pharmacologic
and genetic targeting approaches. Here, CMCs exposed to the pan-HDAC inhibitor
sodium butyrate exhibited induction of a cardiogenic transcriptional program and
heightened expression of myocyte and endothelial lineage-specific markers when
coaxed to differentiate in vitro. Further, shRNA knockdown screens revealed CMCs
depleted of HDAC1 to promote the induction of a cardiogenic transcriptional
program characterized by enhanced expression of cardiomyogenic- and vasculogenic
specific markers, a finding which depended on and correlated with enhanced
acetylation and stabilization of p53. Cardiogenic gene activation and elevated
p53 expression levels observed in HDAC1-depleted CMCs were associated with
improved aptitude to assume a cardiomyogenic/vasculogenic cell-like fate in
vitro. These results suggest that HDAC1 depletion-induced p53 expression alters
CMC cell fate decisions and identify HDAC1 as a potential exploitable target to
facilitate CMC-mediated myocardial repair in ischemic cardiomyopathy. Stem Cells
2016;34:2916-2929.
PMID- 27501842
TI - Epidemiology and Impact of Campylobacter Infection in Children in 8 Low-Resource
Settings: Results From the MAL-ED Study.
AB - BACKGROUND: Enteropathogen infections have been associated with enteric
dysfunction and impaired growth in children in low-resource settings. In a
multisite birth cohort study (MAL-ED), we describe the epidemiology and impact of
Campylobacter infection in the first 2 years of life. METHODS: Children were
actively followed up until 24 months of age. Diarrheal and nondiarrheal stool
samples were collected and tested by enzyme immunoassay for Campylobacter Stool
and blood samples were assayed for markers of intestinal permeability and
inflammation. RESULTS: A total of 1892 children had 7601 diarrheal and 26 267
nondiarrheal stool samples tested for Campylobacter We describe a high prevalence
of infection, with most children (n = 1606; 84.9%) having a Campylobacter
positive stool sample by 1 year of age. Factors associated with a reduced risk of
Campylobacter detection included exclusive breastfeeding (risk ratio, 0.57; 95%
confidence interval, .47-.67), treatment of drinking water (0.76; 0.70-0.83),
access to an improved latrine (0.89; 0.82-0.97), and recent macrolide antibiotic
use (0.68; 0.63-0.74). A high Campylobacter burden was associated with a lower
length-for-age Z score at 24 months (-1.82; 95% confidence interval, -1.94 to
1.70) compared with a low burden (-1.49; -1.60 to -1.38). This association was
robust to confounders and consistent across sites. Campylobacter infection was
also associated with increased intestinal permeability and intestinal and
systemic inflammation. CONCLUSIONS: Campylobacter was prevalent across diverse
settings and associated with growth shortfalls. Promotion of exclusive
breastfeeding, drinking water treatment, improved latrines, and targeted
antibiotic treatment may reduce the burden of Campylobacter infection and improve
growth in children in these settings.
PMID- 27501846
TI - Nanoroughened adhesion-based capture of circulating tumor cells with
heterogeneous expression and metastatic characteristics.
AB - BACKGROUND: Circulating tumor cells (CTCs) have shown prognostic relevance in
many cancer types. However, the majority of current CTC capture methods rely on
positive selection techniques that require a priori knowledge about the surface
protein expression of disseminated CTCs, which are known to be a dynamic
population. METHODS: We developed a microfluidic CTC capture chip that
incorporated a nanoroughened glass substrate for capturing CTCs from blood
samples. Our CTC capture chip utilized the differential adhesion preference of
cancer cells to nanoroughened etched glass surfaces as compared to normal blood
cells and thus did not depend on the physical size or surface protein expression
of CTCs. RESULTS: The microfluidic CTC capture chip was able to achieve a
superior capture yield for both epithelial cell adhesion molecule positive
(EpCAM+) and EpCAM- cancer cells in blood samples. Additionally, the microfluidic
CTC chip captured CTCs undergoing transforming growth factor beta-induced
epithelial-to-mesenchymal transition (TGF-beta-induced EMT) with dynamically down
regulated EpCAM expression. In a mouse model of human breast cancer using EpCAM
positive and negative cell lines, the number of CTCs captured correlated
positively with the size of the primary tumor and was independent of their EpCAM
expression. Furthermore, in a syngeneic mouse model of lung cancer using cell
lines with differential metastasis capability, CTCs were captured from all mice
with detectable primary tumors independent of the cell lines' metastatic ability.
CONCLUSIONS: The microfluidic CTC capture chip using a novel nanoroughened glass
substrate is broadly applicable to capturing heterogeneous CTC populations of
clinical interest independent of their surface marker expression and metastatic
propensity. We were able to capture CTCs from a non-metastatic lung cancer model,
demonstrating the potential of the chip to collect the entirety of CTC
populations including subgroups of distinct biological and phenotypical
properties. Further exploration of the biological potential of metastatic and
presumably non-metastatic CTCs captured using the microfluidic chip will yield
insights into their relevant differences and their effects on tumor progression
and cancer outcomes.
PMID- 27501847
TI - The secondary coordination sphere and axial ligand effects on oxygen reduction
reaction by iron porphyrins: a DFT computational study.
AB - Oxygen reduction reaction (ORR) catalyzed by a bio-inspired iron porphyrin
bearing a hanging carboxylic acid group over the porphyrin ring, and a tethered
axial imidazole ligand was studied by DFT calculations. BP86 free energy
calculations of the redox potentials and pK a's of reaction components involved
in the proton coupled electron transfer (PCET) reactions of the ferric-hydroxo
and -superoxo complexes were performed based on Born-Haber thermodynamic cycle in
conjunction with a continuum solvation model. The comparison was made with iron
porphyrins that lack either in the hanging acid group or axial ligand, suggesting
that H-bond interaction between the carboxylic acid and iron-bound hydroxo, aquo,
superoxo, and peroxo ligands (de)stabilizes the Fe-O bonding, resulting in the
increase in the reduction potential of the ferric complexes. The axial ligand
interaction with the imidazole raises the affinity of the iron-bound superoxo and
peroxo ligands for proton. In addition, a low-spin end-on ferric-hydroperoxo
intermediate, a key precursor for O-O cleavage, can be stabilized in the presence
of axial ligation. Thus, selective and efficient ORR of iron porphyrin can be
achieved with the aid of the secondary coordination sphere and axial ligand
interactions.
PMID- 27501848
TI - Comparison of Clinical Results Following the Use of Drug-Eluting Balloons for a
Bare-Metal Stent and Drug-Eluting Stent Instent Restenosis.
AB - BACKGROUND: Drug-eluting balloons (DEBs) have emerged as a potential alternative
to current treatments of instent restenosis (ISR). The study aims to investigate
the clinical outcomes of a DEB angioplasty to treat bare-metal stent (BMS) ISR
and drug-eluting stent (DES) ISR at 1-year clinical follow-up period. METHODS:
Between November 2011 and December 2014, 312 patients were diagnosed with
coronary artery ISR at our hospital. A total of 426 coronary ISR lesions were
treated with DEBs. The clinical outcomes, including target lesion
revascularization (TLR), myocardial infarction, stroke, cardiovascular mortality,
and all-cause mortality were compared between the BMS-ISR group and DES-ISR
group. Propensity score matched analysis was used to minimize bias. RESULTS: The
average age of the patients was 64.99 +/- 10.35 years, and 76.9% of the patients
were male. After multivariate Cox regression analyses about 1-year recurrent
restenosis in DES-ISR group, only end stage renal disease (ESRD) (P = 0.047) and
previous DEB failure (P < 0.001) were identified with significant difference.
After propensity score matched analysis, the bias of baseline characteristics
showed no significant difference. The DES-ISR group experienced more myocardial
infarctions (2.8% vs 8.3%, P = 0.075), more TLR (8.1% vs 15.4%, P = 0.051),
especially at nonostial lesion (5.7% vs 14.9%, P = 0.030) than the BMS-ISR group.
Higher incidence of major cardiac cerebral adverse events happened in the DES-ISR
group. (11.7% vs 22.1 %, P = 0.038) CONCLUSION: During the 1-year follow-up
period, DEBs angioplasty for BMS-ISR had better clinical outcomes and less TLR
than DES-ISR. ESRD and previous DEB failure were associated to TLR in DES-ISR
group.
PMID- 27501849
TI - Calibration of parameters for cardiovascular models with application to arterial
growth.
AB - We present a computational framework for the calibration of parameters describing
cardiovascular models with a focus on the application of growth of abdominal
aortic aneurysms (AAA). The growth rate in this sort of pathology is considered a
critical parameter in the risk management and is an essential indicator for the
assessment of surveillance intervals. Parameters describing growth of AAAs are
not measurable directly and need to be estimated from available data often given
by medical imaging technologies. Registration procedures often applied in
standard workflows of parameter identification to extract the image encoded
information are a source of significant systematic error. The concept of surface
currents provides means to effectively avoid this source of errors by
establishing a mathematical framework to compare surface information, directly
accessible from image data. By utilizing this concept it is possible to inversely
estimate growth parameters using sophisticated numerical models of AAAs from
measurements available as surface information. In this work we present a
framework to obtain spatial distributions of parameters governing growth of
arterial tissue, and we show how the use of surface currents can significantly
improve the results. We further present the application to patient specific
follow-up data resulting in a spatial map of volumetric growth rates enabling,
for the first time, prediction of further AAA expansion.
PMID- 27501850
TI - Programmed cell death-1 blockade enhances response to stereotactic radiation in
an orthotopic murine model of hepatocellular carcinoma.
AB - AIM: Small, solitary hepatocellular carcinoma is curable with stereotactic
radiation or other methods of tumor ablation, however, regional and systemic
tumor recurrence occurs in over 70% of patients. Here we describe the ability of
immunoradiotherapy to induce an antitumor immune response and delay the growth of
tumors in immunocompetent mice. METHODS: A syngeneic hepatocellular carcinoma
cell line (Hep-55.1c) was injected directly into the livers of C57BL/6 mice using
ultrasound guidance, then tumors were treated with stereotactic radiation using a
Small Animal Radiation Research Platform with computed tomography guidance.
RESULTS: Delivery of three doses of 250 MUg anti-programmed cell death protein-1
(alphaPD-1) antibody concurrently with 30 Gy stereotactic body radiation therapy
in three fractions reduced the growth rate of tumors and improved survival (P <
0.05). Combined treatment was associated with increased CD8+ cytotoxic T cells in
the tumor; depletion of CD8 T cells eliminated the efficacy of combined
treatment. Combined treatment also induced expression of programmed cell death-1
ligand expression on tumor-infiltrating macrophages, and the tumors grew rapidly
after alphaPD-1 treatment was discontinued. CONCLUSIONS: Tumor response to
stereotactic radiation can be augmented by concurrent treatment with alphaPD-1.
The efficacy of this combination therapy was transient, however, and treatment
induced markers of adaptive immune resistance. These data are promising, but also
indicate that mechanisms of immune resistance will need to be durably overcome
for this combination to generate lasting immunity to protect against tumor
recurrence.
PMID- 27501851
TI - Impact of treatment duration of neoadjuvant FIRINOX in patients with borderline
resectable pancreatic cancer: a pilot trial.
AB - PURPOSE: The aim of this pilot study is to confirm the safety and efficacy of
neoadjuvant therapy and also treatment duration efficacy using modified
FOLFIRINOX for patients with borderline resectable pancreatic cancer (BRPC).
METHODS: The study is a prospective multicenter pilot trial conducted on patients
with BRPC. Intervention for clinical trials: Modified FOLFIRINOX (without bolus 5
FU and LV, also decreased the dose of irinotecan; FIRINOX) was given to the first
five patients in the 4-cycle group of the regimen and next five patients in the 8
cycle group. The primary end point was the toxicity of the therapy and one of the
secondary end points were the optimal duration. RESULTS: The overall rate of
grade 3 and 4 events was 80 %: 3 patients (60 %) in the four-cycle group and five
patients (100 %) in the eight-cycle group had grade 3 or 4 adverse events. There
was no incidence of serious adverse effect such as febrile neutropenia, sepsis,
liver abscess or uncontrollable diarrhea. There was no clinically relevant
morbidity presented in patients who underwent surgery. R0 rates by intention to
treat were 60.0 % in the four-cycle group and 40 % in the eight-cycle group (P =
0.999). The histopathologic treatment effect based on the Evans grade revealed
grade I (n = 1), IIa (n = 3) in the four-cycle group and grade I (n = 2), IIa (n
= 1) in the eight-cycle group. CONCLUSIONS: FIRINOX therapy was feasible and safe
for strictly selected patients with BRPC. Four cycles of FIRINOX would be
sufficient for patients with BRPC as neoadjuvant therapy.
PMID- 27501852
TI - Repositioning organohalogen drugs: a case study for identification of potent B
Raf V600E inhibitors via docking and bioassay.
AB - Drug repositioning has been attracting increasingly attention for its advantages
of reducing costs and risks. Statistics showed that around one quarter of the
marketed drugs are organohalogens. However, no study has been reported, to the
best of our knowledge, to aim at efficiently repositioning organohalogen drugs,
which may be attributed to the lack of accurate halogen bonding scoring function.
Here, we present a study to show that two organohalogen drugs were successfully
repositioned as potent B-Raf V600E inhibitors via molecular docking with halogen
bonding scoring function, namely D(3)DOCKxb developed in our lab, and bioassay.
After virtual screening by D(3)DOCKxb against the database CMC (Comprehensive
Medicinal Chemistry), 3 organohalogen drugs that were predicted to form strong
halogen bonding with B-Raf V600E were purchased and tested with ELISA-based
assay. In the end, 2 of them, rafoxanide and closantel, were identified as potent
inhibitors with IC50 values of 0.07 MUM and 1.90 MUM, respectively, which are
comparable to that of vemurafenib (IC50: 0.17 MUM), a marketed drug targeting B
Raf V600E. Single point mutagenesis experiments confirmed the conformations
predicted by D(3)DOCKxb. And comparison experiment revealed that halogen bonding
scoring function is essential for repositioning those drugs with heavy halogen
atoms in their molecular structures.
PMID- 27501854
TI - Mild Palladium Catalyzed ortho C-H Bond Functionalizations of Aniline
Derivatives.
AB - This account collects the developments and transformations which avoid the
utilization of harsh reaction conditions in the field of palladium catalyzed,
ortho-directed C-H activation of aniline derivatives from the first attempts to
up-to-date results, including the results of our research laboratory. The
discussed functionalizations performed under mild conditions include acylation,
olefination, arylation, alkylation, alkoxylation reactions. Beside the
optimization studies and the synthetic applications mechanistic investigations
are also presented.
PMID- 27501853
TI - Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced
Shock.
AB - Animal studies and human case reports show promise in using lipid rescue to treat
refractory calcium channel antagonist toxicity. However, the majority of research
and clinical experience has focused on non-dihydropyridine agents. Thus, we
sought to investigate the value of lipid emulsion (ILE) therapy for
dihydropyridine-induced shock. This IACUC-approved study utilized seven swine
that were sedated with alpha-chloralose, mechanically ventilated, and
instrumented for drug delivery and hemodynamic measures. After stabilization and
basal measures, nifedipine (0.01875 mg/kg/min) was infused until imminent cardiac
arrest (seizure, end tidal CO2 < 10 mmHg, bradydysrhythmia, or pulseless
electrical activity). Animals then received a 7 mL/kg bolus of 20% lipid emulsion
via central catheter. Lipid circulation was visually confirmed by the presence of
fat in peripheral arterial blood. Hemodynamics were continuously monitored until
10 min after lipid bolus. Surviving animals were euthanized. Pre- and post-lipid
treatment parameters were analyzed using the Wilxocon signed rank test (p <0.05
significant). Nifedipine toxicity was characterized by vasodilatory hypotension,
impaired vascular contractility, and tachycardia with terminal bradycardia. The
median time to imminent cardiac arrest from start of nifedipine infusion was 218
min. Lipid treatment did not improve hemodynamics or restore circulation in any
animal. There was no benefit from lipid rescue in this model of nifedipine
toxicity. Further study of ILE for dihydropyridine toxicity is warranted but
initial animal model results are not promising.
PMID- 27501855
TI - Environmental selection of planktonic methanogens in permafrost thaw ponds.
AB - The warming and thermal erosion of ice-containing permafrost results in thaw
ponds that are strong emitters of methane to the atmosphere. Here we examined
methanogens and other Archaea, in two types of thaw ponds that are formed by the
collapse of either permafrost peat mounds (palsas) or mineral soil mounds
(lithalsas) in subarctic Quebec, Canada. Using high-throughput sequencing of a
hypervariable region of 16S rRNA, we determined the taxonomic structure and
diversity of archaeal communities in near-bottom water samples, and analyzed the
mcrA gene transcripts from two sites. The ponds at all sites were well
stratified, with hypoxic or anoxic bottom waters. Their archaeal communities were
dominated by Euryarchaeota, specifically taxa in the methanogenic orders
Methanomicrobiales and Methanosarcinales, indicating a potentially active
community of planktonic methanogens. The order Methanomicrobiales accounted for
most of the mcrA transcripts in the two ponds. The Archaeal communities differed
significantly between the lithalsa and palsa ponds, with higher alpha diversity
in the organic-rich palsa ponds, and pronounced differences in community
structure. These results indicate the widespread occurrence of planktonic,
methane-producing Archaea in thaw ponds, with environmental selection of taxa
according to permafrost landscape type.
PMID- 27501856
TI - Can we improve the therapy of Clostridium difficile infection in elderly
patients?
AB - BACKGROUND: Clostridium difficile infection (CDI) is becoming a serious problem
predominantly in geriatric patients, who are a significant risk group. The goal
of this study was to evaluate the risk factors for mortality in CDI patients and
to construct a binary logistic regression model that describes the probability of
mortality in geriatric patients suffering from CDI. METHODS: In this
retrospective study, we evaluated a group of 235 patients over 65 years of age
with confirmed diagnoses of CDI, hospitalized at the Department of Internal
Medicine, Geriatrics and General Practice, Brno, from January 2008 to December
2013. The examined group comprised 148 women (63 %) and 87 men (37 %). For the
diagnosis of CDI, confirmation of A and B toxins in the patients' stool or an
autopsy confirmation was crucial. RESULTS: The impact of antibiotic therapy on
the increased incidence of CDI was clearly confirmed in our study group when
examining patients' histories. Other risk factors included cerebrovascular
disease, dementia, the presence of pressure ulcers, and immobility. Our new model
consisted of a combination of the following parameters: the number of antibiotics
used (from patients' history), nutritional status (Mini Nutritional Assessment
short-form test), presence of pressure ulcers, and occurrence of fever.
CONCLUSION: Our logistic regression model may predict mortality in geriatric
patients suffering from CDI. This could help improve the therapeutic process.
PMID- 27501857
TI - Tuning the Drug Loading and Release of DNA-Assembled Gold-Nanorod
Superstructures.
AB - The use of DNA to assemble inorganic nanoparticles into superstructures is an
emerging strategy to build non-toxic delivery vehicles for targeting diseases in
the body. The impact of the core-satellite nanosystem design in mediating drug
storage, drug release (via heat), and killing of HeLa cells in culture is
investigated.
PMID- 27501858
TI - Helicity-dependent photocurrent induced by the in-plane transverse electric
current in an InAs quantum well.
AB - We report the observation of a new type of helicity-dependent photocurrent
induced by an in-plane transverse direct electric current in an InAs quantum
well. The amplitude of the photocurrent depends linearly on the transverse
current. Moreover, the observed incident azimuth-angle dependence of this
photocurrent is different from that induced by the circular photogalvanic effect.
This new photocurrent appears as a result of an asymmetrical carrier distribution
in both the conduction and valence bands induced by the transverse current. The
photoexcited carrier density created by interband transition processes is thus
modulated and leads to the observed new azimuth-angle dependence. The observed
efficient generation of the helicity-dependent photocurrent offers an effective
approach to manipulate electron spins in two-dimensional semiconductor systems
with the added advantage of electrical control of the spin-related photocurrent
in spintronic applications.
PMID- 27501859
TI - The acceptability of three vaccine injections given to infants during a single
clinic visit in South Africa.
AB - BACKGROUND: The Expanded Programme on Immunisation (EPI) has increased the number
of antigens and injections administered at one visit. There are concerns that
more injections at a single immunisation visit could decrease vaccination
coverage. We assessed the acceptability and acceptance of three vaccine
injections at a single immunisation visit by caregivers and vaccinators in South
Africa. METHODS: A mixed methods exploratory study of caregivers and vaccinators
at clinics in two provinces of South Africa was conducted. Quantitative and
qualitative data were collected using questionnaires as well as observations of
the administration of three-injection vaccination sessions. RESULTS: The sample
comprised 229 caregivers and 98 vaccinators. Caregivers were satisfied with the
vaccinators' care (97 %) and their infants receiving immunisation injections (93
%). However, many caregivers, (86 %) also felt that three or more injections were
excessive at one visit. Caregivers had limited knowledge of actual vaccines
provided, and reasons for three injections. Although vaccinators recognised the
importance of informing caregivers about vaccination, they only did this
sometimes. Overall, acceptance of three injections was high, with 97 % of
caregivers expressing willingness to bring their infant for three injections
again in future visits despite concerns about the pain and discomfort that the
infant experienced. Many (55 %) vaccinators expressed concern about giving three
injections in one immunisation visit. However, in 122 (95 %) observed three
injection vaccination sessions, the vaccinators administered all required
vaccinations for that visit. The remaining seven vaccinations were not completed
because of vaccine stock-outs. CONCLUSIONS: We found high acceptance by
caregivers and vaccinators of three injections. Caregivers' poor understanding of
reasons for three injections resulted from limited information sharing by
vaccinators for caregivers. Acceptability of three injections may be improved
through enhanced vaccinator-caregiver communication, and improved management of
infants' pain. Vaccinator training should include evidence-informed ways of
communicating with caregivers and reducing injection pain. Strategies to improve
acceptance and acceptability of three injections should be rigorously evaluated
as part of EPI's expansion in resource-limited countries.
PMID- 27501860
TI - 2-(Maleimidomethyl)-1,3-Dioxanes (MD): a Serum-Stable Self-hydrolysable
Hydrophilic Alternative to Classical Maleimide Conjugation.
AB - The vast majority of antibody-drug conjugates (ADC) are prepared through amine-to
thiol conjugation. To date, N-Succinimidyl-4-(maleimidomethyl)
cyclohexanecarboxylate (SMCC) has been one of the most frequently applied
reagents for the preparation of ADC and other functional conjugates. However,
SMCC-based conjugates suffer from limited stability in blood circulation and from
a hydrophobic character of the linker, which may give rise to major
pharmacokinetic implications. To address this issue, we have developed a
heterobifunctional analogue of a SMCC reagent, i.e., sodium 4-(maleimidomethyl)
1,3-dioxane-5-carbonyl)oxy)-2,3,5,6- tetrafluorobenzenesulfonate (MDTF) for amine
to-thiol conjugation. By replacing the cyclohexyl ring in the SMCC structure with
the 1,3-dioxane, we increased the hydrophilicity of the linker. A FRET probe
based on MD linker was prepared and showed superior stability compared to the MCC
linker in human plasma, as well as in a variety of aqueous buffers. A detailed
investigation demonstrated an accelerated succinimide ring opening for MD linker,
resulting in stabilized conjugates. Finally, the MDTF reagent was applied for the
preparation of serum stable antibody-dye conjugate.
PMID- 27501861
TI - A la Peche aux Moules.
AB - In a recent manuscript, Goff and collaborators (Metzger et al. 2016) reported
data arguing for the spread of contagious cancer cells among different species of
shellfish. Although horizontal transmission of cancer cells has been observed in
a few cases in higher organisms, it appears to be rather frequent among molluscs.
Recent evidence supports the concept of inter-species horizontal infectious
transmission of cancer cells both in molluscs but also in mammals, including
humans.
PMID- 27501862
TI - Asthma-COPD overlap syndrome (ACOS) vs 'pure' COPD: a distinct phenotype?
AB - BACKGROUND: Some studies suggest that asthma-COPD overlap syndrome (ACOS) is
associated with worse outcomes than chronic obstructive pulmonary disease (COPD).
The goal of this study was to further explore the clinical characteristics and
survival of patients with ACOS identified in a real-life cohort of patients with
COPD. METHODS: Data from the French COPD cohort 'INITIATIVES BronchoPneumopathie
Chronique Obstructive' (n = 998 patients) were analyzed to assess the frequency
of ACOS defined as a physician diagnosis of asthma before the age of 40 years and
to analyze its impact. Univariate analyses were performed to assess the
relationship between ACOS and sociodemographic characteristics, risk factors
(smoking, occupational exposure, atopic diseases), symptoms (chronic bronchitis,
dyspnea-modified Medical Research Council scale and baseline dyspnea index),
quality of life (QoL), mood disorders, exacerbations, comorbidities, lung
function, prescribed treatment, and survival. RESULTS: ACOS was diagnosed in 129
patients (13%). In multivariate analyses, ACOS was associated negatively with
cumulative smoking (odds ratio [OR]: 0.992; 95% CI 0.984-1.000 per pack-year) and
positively with obesity: OR: 1.97 [1.22-3.16], history of atopic disease (hay
fever: OR: 5.50 [3.42-9.00] and atopic dermatitis: OR 3.76 [2.14-6.61]), and drug
use (LABA + ICS: 1.86 [1.27-2.74], antileukotrienes 4.83 [1.63-14.34],
theophylline: 2.46 [1.23-4.91], and oral corticosteroids: [2.99;.1.26-7.08]). No
independent association was found with dyspnea, QoL, exacerbations, and
mortality. CONCLUSIONS: Compared to 'pure' COPD patients, patients with ACOS
exhibit lower cumulative smoking, suffer more from obesity and atopic diseases,
and use more asthma treatments. Disease severity (dyspnea, QoL, exacerbations,
comorbidities) and prognosis (mortality) are not different from 'pure' COPD
patients.
PMID- 27501863
TI - Burden of atrial fibrillation: a retrospective review of patients presenting to
acute medical services.
AB - BACKGROUND: Atrial fibrillation (AF) is a major risk factor for stroke and is
associated with increased stroke severity and greater morbidity and mortality.
Anticoagulation is highly effective for preventing episodes of thromboembolism
but remains under-utilised. AIMS: The aim of this review was to estimate the
short-term risk of thromboembolic events in patients presenting with an acute
medical illness, to assess rates of anticoagulation in eligible patients with AF
and to describe physician decisions when prescribing anticoagulation in a
hospital setting. METHODS: A retrospective cohort analysis of patients with AF
presenting to acute medical services at Wellington Regional Hospital between 1
January 2012 and 31 December 2012 was performed. RESULTS: A total of 751 patient
presentations with AF was identified; 613 unique patient encounters were eligible
for analysis, and 38.8% of patients with a CHA2 DS2 -VASc score >=2 were
discharged after anticoagulation. The mean CHA2 DS2 -VASc score was 4.03 (SD =
1.94). The CHA2 DS2 -VASc score was not associated with being started on
anticoagulation, odds ratio 1.16 (95% confidence interval = 0.83-1.61), P = 0.38,
but age by decade older was associated with a reduced likelihood of being started
on anticoagulation, odds ratio 0.61 (95% confidence interval = 0.41-0.89), P =
0.01. In untreated patients with a CHA2 DS2 -VASc score >=2, the most frequently
documented reasons not to initiate anticoagulation were decision deferred to the
primary care physician, 15.6%; fall risk or frailty, 7.2%; and high bleeding
risk, 6.6%. However, no reason was documented in 56.9%. The thromboembolic rate
in patients discharged without anticoagulation within 3 months of presentation to
acute medical services was 7/330 (2.1%). CONCLUSION: Anticoagulation for stroke
prevention in AF remains under-utilised in eligible patients presenting to acute
medical services at a tertiary-level hospital.
PMID- 27501864
TI - Iron intakes and status of 2-year-old children in the Cork BASELINE Birth Cohort
Study.
AB - Young children are at risk of iron deficiency and subsequent anaemia, resulting
in long-term consequences for cognitive, motor and behavioural development. This
study aimed to describe the iron intakes, status and determinants of status in 2
year-old children. Data were collected prospectively in the mother-child Cork
BASELINE Birth Cohort Study from 15 weeks' gestation throughout early childhood.
At the 24-month assessment, serum ferritin, haemoglobin and mean corpuscular
volume were measured, and food/nutrient intake data were collected using a 2-day
weighed food diary. Iron status was assessed in 729 children (median [IQR] age:
2.1 [2.1, 2.2] years) and 468 completed a food diary. From the food diary, mean
(SD) iron intakes were 6.8 (2.6) mg/day and 30% had intakes < UK Estimated
Average Requirement (5.3 mg/day). Using WHO definitions, iron deficiency was
observed in 4.6% (n = 31) and iron deficiency anaemia in five children (1.0%).
Following an iron series workup, five more children were diagnosed with iron
deficiency anaemia. Twenty-one per cent had ferritin concentrations <15 ug/L.
Inadequate iron intakes (OR [95% CI]: 1.94 [1.09, 3.48]) and unmodified cows'
milk intakes >= 400 mL/day (1.95 [1.07, 3.56]) increased the risk of low iron
status. Iron-fortified formula consumption was associated with decreased risk
(0.21 [0.11, 0.41] P < 0.05). In this, the largest study in toddlers in Europe, a
lower prevalence of low iron status was observed than in previous reports.
Compliance with dietary recommendations to limit cows' milk intakes in young
children and consumption of iron-fortified products appears to have contributed
to improved iron status at two years.
PMID- 27501866
TI - Isolation, identification and characterisation of ballan wrasse Labrus bergylta
plasma pigment.
AB - This study confirmed that observations of blue-green colouration in plasma
fractions of the ballan wrasse Labrus bergylta were caused by the linear tetra
pyrrole biliverdin and that the molecule was of the physiologically relevant
IXalpha isomer. Accumulation appears driven by chromogenic association with an
unknown protein moiety which precludes enzymatic reduction and would suggest
active management. It was demonstrated that the pigment did not fluctuate
relative to ontogeny, or indeed binary gender in the species of interest, but
mobilisation and depletion in the subset of individuals undergoing sex change at
the time of study supports a potential association with gender inversion
processes. It is of note that although biliverdin does have some effect on
external colouration, the evidence is indicative that crypsis is a supplementary
function thus other factors must be considered.
PMID- 27501867
TI - A tale of loss of privilege, resilience and change: the impact of the economic
crisis on physicians and medical services in Portugal.
AB - That the current economic crisis is having an impact on population health and
healthcare utilisation across Europe is fairly established; how national health
systems and markets are reacting is however still poorly understood. Drawing from
the economic literature we conducted 21 interviews with physicians, policy-makers
and healthcare managers in Portugal, to explore their perceptions on the impact
of the crisis on the country's market medical services, on physicians'
motivation, and the ensuing coping strategies. Interviews were recorded,
transcribed and analysed using NVivo software. We show that despite the crisis,
few physicians reported considering leaving the public sector and the country,
and very diverse coping strategies are emerging, depending on the respective
employment institutions and seniority. In spite of the changes in patient case
mix, demand for medical services may not have necessarily increased, having
shifted from public to private, with many highlighting the contribution of the
current crisis in consolidating the private sector. In order to maintain their
pre-crisis living standards amidst deteriorating salaries and increasing
controls, hospital physicians have resorted to strategies such as shifting hours
to the private, and primary care ones to anticipating their retirement. Migration
was reported to be an option only for the younger and older doctors. Our study
suggests the existence of resilience among Portuguese physicians and in the
country's market for medical services, which, if corroborated by further
research, will need to be taken into account by national health policies.
PMID- 27501865
TI - Changes in total plasma and serum N-glycome composition and patient-controlled
analgesia after major abdominal surgery.
AB - Systemic inflammation participates to the complex healing process occurring after
major surgery, thus directly affecting the surgical outcome and patient recovery.
Total plasma N-glycome might be an indicator of inflammation after major surgery,
as well as an anti-inflammatory therapy response marker, since protein
glycosylation plays an essential role in the inflammatory cascade. Therefore, we
assessed the effects of surgery on the total plasma N-glycome and the association
with self-administration of postoperative morphine in two cohorts of patients
that underwent major abdominal surgery. We found that plasma N-glycome undergoes
significant changes one day after surgery and intensifies one day later, thus
indicating a systemic physiological response. In particular, we observed the
increase of bisialylated biantennary glycan, A2G2S[3,6]2, 12 hours after surgery,
which progressively increased until 48 postoperative hours. Most changes occurred
24 hours after surgery with the decrease of most core-fucosylated biantennary
structures, as well as the increase in sialylated tetraantennary and
FA3G3S[3,3,3]3 structures. Moreover, we observed a progressive increase of
sialylated triantennary and tetraantennary structures two days after surgery,
with a concomitant decrease of the structures containing bisecting N
acetylglucosamine along with bi- and trisialylated triantennary glycans. We did
not find any statistically significant association between morphine consumption
and plasma N-glycome.
PMID- 27501869
TI - Comparative analysis of in vitro characteristics of fresh and frozen-thawed
urethral and epididymal spermatozoa from cats (Felis domesticus).
AB - The first aim of this study was to provide a comprehensive analysis of structural
and functional features of spermatozoa in semen collected from the same cat by
two methods: urethral catheterization and epididymis slicing. The second aim was
to assess if feline urethral (CT) and epididymal (EP) spermatozoa undergo the
same changes during cryopreservation and to compare the postthaw characteristics
of spermatozoa collected by the two methods. In the first phase, CT and EP semen
were collected from 20 cats, and sperm motility, viability, morphology, computer
assisted sperm analysis (CASA) parameters, membrane and acrosome integrity,
mitochondrial potential, lipid peroxidation, and chromatin status were assessed.
In the second phase, both types of semen collected from 10 cats were
cryopreserved, thawed, and the same sperm parameters were assessed as in fresh
semen. Fresh CT spermatozoa (phase I) showed higher (P < 0.05) motility
(subjective: median 75.0% vs. 62.5%; by CASA: mean +/- SD 60.2 +/- 10.7% vs. 43.1
+/- 16.7%), morphology (mean +/- SD, 57.5 +/- 9.6% vs. 45.2 +/- 15.9%), and
membrane integrity (median live: 89.2% vs. 79.8%). Other parameters were not
different between CT and EP spermatozoa. After cryopreservation (phase II),
spermatozoa from both types of semen did not differ significantly, except for
lipid peroxidation of live sperm cells (median CT: 3.5%, EP: 1.7%, P < 0.05).
Urethral and EP spermatozoa showed a similar, significant drop in motility (CT to
18.6 +/- 10.3% and EP to 21.6 +/- 12.1%, P < 0.05), progressive motility (CT to
6.8 +/- 5.9% and EP to 8.3 +/- 8.8%, P < 0.05), and rapid movement (from 34.3 +/-
20.6% to 8.5 +/- 7.0% in CT and from 26.0 +/- 14.7% to 10.1 +/- 10.4% in EP, P <
0.05), whereas other motion characteristics assessed by CASA were not affected (P
> 0.05). The strongest change after cryopreservation was noted in high
mitochondrial potential (median CT: 1.3%, EP: 2.2%). Although cryopreservation
increased acrosome damage and lipid peroxidation, the level of these changes in
the population of live sperm cells remained low (median acrosome damage: CT:
3.3%, EP: 4.5%, lipid peroxidation CT: 3.5%, EP: 1.7%). Cryopreservation did not
affect chromatin structure (median percent DNA fragmentation index, CT: 3.3%, EP:
2.3%). In this study, we confirmed that urethral catheterization for collection
of semen allows the retrieval of spermatozoa with quality equally good as in
those obtained by epididymal slicing. Spermatozoa from both types of semen
collected showed similar characteristics after freezing/thawing so both types can
be used for semen banking.
PMID- 27501868
TI - Local adaptation of a bacterium is as important as its presence in structuring a
natural microbial community.
AB - Local adaptation of a species can affect community composition, yet the
importance of local adaptation compared with species presence per se is unknown.
Here we determine how a compost bacterial community exposed to elevated
temperature changes over 2 months as a result of the presence of a focal
bacterium, Pseudomonas fluorescens SBW25, that had been pre-adapted or not to the
compost for 48 days. The effect of local adaptation on community composition is
as great as the effect of species presence per se, with these results robust to
the presence of an additional strong selection pressure: an SBW25-specific virus.
These findings suggest that evolution occurring over ecological time scales can
be a key driver of the structure of natural microbial communities, particularly
in situations where some species have an evolutionary head start following large
perturbations, such as exposure to antibiotics or crop planting and harvesting.
PMID- 27501870
TI - Reproductive performance of Japanese Black cattle: Association with herd size,
season, and parity in commercial cow-calf operations.
AB - The Japanese Black is the most common breed of beef cattle in Japan. However,
only limited data are available on the associations of season, parity, and herd
size with reproductive performance in Japanese Black cattle. Therefore, the
objective of the present study was to determine the associations of these factors
with reproductive performance parameters, such as the calving to first service
interval (CFSI) and first service conception rate in Japanese Black cattle. Data
were collected from 34,763 calvings in 13,186 animals from 826 commercial cow
calf operations in the Miyazaki prefecture, which is located on the south eastern
coast of Kyushu, Japan. This region has a temperate climate with warm humid
summers and cold winters. All cattle were reared intensively, and the animals
were housed in free stalls throughout their lives. The mean number of cows per
farm was 18 (range, 1-454). All animals were bred by artificial insemination.
Herds were classified into three groups based on size: small (<=10 cows),
intermediate (11-50 cows), and large (>=51 cows). The mean (+/-SD) parity, CFSI,
and the first service conception rate were 4.9 +/- 2.9, 80.0 +/- 46.2 days, and
53.5 +/- 49.9%, respectively. Cows that calved in the spring (March to May) and
winter (December to February) had the longest CFSI (P < 0.05). The CFSI in first
parity cows was shorter than in cows at parity 7 or higher (P < 0.05). Cows in
large herds had an approximately 10 days shorter mean CFSI than those in small
herds (P < 0.05). Cows inseminated in the winter or spring had an approximately
5% points lesser first-service conception rate (FSCR) than those inseminated
during the summer (June to August) or autumn (September to November; P < 0.05).
As parity increased from 1 to 9, FSCR decreased from 60.0% to 43.1% (P < 0.05).
Cows in small herds had a lesser FSCR than those in intermediate and large herds
(P < 0.05). In summary, decreased reproductive performance in intensively reared
Japanese Black cattle was associated with calving and artificial insemination
during the winter and spring, greater parity, and small herd size.
PMID- 27501871
TI - Complexities of follicle deviation during selection of a dominant follicle in Bos
taurus heifers.
AB - Follicle deviation during a follicular wave is a continuation in growth rate of
the dominant follicle (F1) and decreased growth rate of the largest subordinate
follicle (F2). The reliability of using an F1 of 8.5 mm to represent the
beginning of expected deviation for experimental purposes during waves 1 and 2 (n
= 26 per wave) was studied daily in heifers. Each wave was subgrouped as follows:
standard subgroup (F1 larger than F2 for 2 days preceding deviation and F2 > 7.0
mm on the day of deviation), undersized subgroup (F2 did not attain 7.0 mm by the
day of deviation), and switched subgroup (F2 larger than F1 at least once on the
2 days before or on the day of deviation). For each wave, mean differences in
diameter between F1 and F2 changed abruptly at expected deviation in the standard
subgroup but began 1 day before expected deviation in the undersized and switched
subgroups. Concentrations of FSH in the wave-stimulating FSH surge and an
increase in LH centered on expected deviation did not differ among subgroups.
Results for each wave indicated that (1) expected deviation (F1, 8.5 mm) was a
reliable representation of actual deviation in the standard subgroup but not in
the undersized and switched subgroups; (2) concentrations of the gonadotropins
normalized to expected deviation were similar among the three subgroups,
indicating that the day of deviation was related to diameter of F1 and not F2;
and (3) defining an expected day of deviation for experimental use should
consider both diameter of F1 and the characteristics of deviation.
PMID- 27501872
TI - The effect of ovine oocyte vitrification on expression of subset of genes
involved in epigenetic modifications during oocyte maturation and early embryo
development.
AB - Apart from ultrastructural damages in oocytes subjected to cryopreservation
procedures, little is known about the status of epigenetic modification and
chromatin remodeling in vitrified oocytes. In present study, the expression
patterns of eight genes involved in epigenetic modification (HAT1, HDAC1,
SUV39H1, DNMT1, and DNMT3b), chromatin remodeling (HMGN3a and SMARCAL1), and
transcription (STAT3), were investigated in fresh and vitrified germinal vesicle
and metaphase II oocytes and their resulting embryos at 2 to 7 cells, 8 to 16
cells, morula, and blastocyst stages. The mRNA relative abundance was quantified
by reverse transcriptase real-time polymerase chain reaction, as fold change
relative to the value obtained for fresh germinal vesicle oocytes. Vitrified
oocytes showed lower cleavage (38.1% vs. 95.5%, P < 0.001) and development to
blastocyst (8.2% vs. 50.8%, P < 0.001) compared with controls. In both fresh and
vitrified groups, the genes expressions in oocytes were lower than cleaving
embryos, with an exception of HMGN3a. Compared with fresh derived embryos, in
vitrified groups, the overall expressions of HMGN3a and HDAC1 were decreased,
whereas the expressions of STAT3, SMARCAL1, and DNMT3B were increased.
Altogether, despite some differences in expression pattern of some genes, the
overall pattern of increase and/or decrease in gene expression was almost the
same in most of the genes studied between vitrified and fresh groups. Thus, apart
from some mismatch in pattern of genes expression in a number of cases, the
difference in magnitude and/or primacy and recency in reaching to the maximum
expression, in association to embryonic genome activation, between fresh and
vitrified groups, might be the reason for the lower developmental competence of
vitrified-warmed oocytes compared with fresh ones.
PMID- 27501873
TI - Identification of the pregnancy-associated glycoprotein family (PAGs) and some
aspects of placenta development in the European moose (Alces alces L.).
AB - This study describes the identification and a broad-based characterization of the
pregnancy-associated glycoprotein (PAG) genes expressed in the
synepitheliochorial placenta of the Alces alces (Aa; N = 51). We used: (1) both
size measurements (cm) of various Aa embryos/fetuses (crown-rump length) and
placentomes (PLCs); (2) PCR, Southern and sequencing; (3) Western-blot for total
placental glycoproteins; (4) deglycosylation of total cotyledonary proteins; and
(5) double heterologous IHC for cellular immune-localization of the PAGs as
pregnancy advanced (50-200 days post coitum). The crown-rump length and PLC size
measurements permitted a novel pattern estimation of various pregnancy stages in
wild Aa. The PLC number varied (5-21) and was the greatest at the mid and late
stages of gestation in females bearing singletons or twins. The genomic existence
of the identified PAG-like family was named AaPAG-L. Amplicon profiles of the
AaPAG-L varied in the number and length (118-2000 bp). Southern with porcine cDNA
probes confirmed specificity and revealed dominant AaPAG-L amplicons in males and
females. Nucleotide sequences of the AaPAG-L amplicons shared 86.27% homology
with the bovine PAG1 (bPAG1) gene. Amino acid AaPAG sequences revealed in silico
88.23% to 100% homology with the bPAG1 precursor. Western-blots revealed a
dominant mature 55 kDa AaPAG fraction, and the major ~48 kDa glycosylated form
that was deglycosylated to ~44 kDa. The AaPAG-Ls was immuno-localized to mono-
and bi-nucleated trophectodermal cells (TRD-chorionic epithelium), where signal
intensity resembled intense TRD proliferation within developing PLCs as pregnancy
advanced. This is the first study identifying the AaPAG-L family in the largest
representative among the Cervidae.
PMID- 27501874
TI - Impact of photon cross section uncertainties on Monte Carlo-determined depth-dose
distributions.
AB - This work studies the impact of systematic uncertainties associated to
interaction cross sections on depth dose curves determined by Monte Carlo
simulations. The corresponding sensitivity factors are quantified by changing
cross sections by a given amount and determining the variation in the dose. The
influence of total and partial photon cross sections is addressed. Partial cross
sections for Compton and Rayleigh scattering, photo-electric effect, and pair
production have been accounted for. The PENELOPE code was used in all
simulations. It was found that photon cross section sensitivity factors depend on
depth. In addition, they are positive and negative for depths below and above an
equilibrium depth, respectively. At this depth, sensitivity factors are null. The
equilibrium depths found in this work agree very well with the mean free path of
the corresponding incident photon energy. Using the sensitivity factors reported
here, it is possible to estimate the impact of photon cross section uncertainties
on the uncertainty of Monte Carlo-determined depth dose curves.
PMID- 27501875
TI - Iterative image reconstruction using modified non-local means filtering for
limited-angle computed tomography.
AB - PURPOSE: Limited-angle CT imaging is an effective technique to reduce radiation.
However, existing image reconstruction methods can effectively reduce streak
artifacts but fail to suppress those artifacts around edges due to incomplete
projection data. Thus, a modified NLM (mNLM) based reconstruction method is
proposed. METHODS: Since the artifacts around edges mainly exist in local
position, it is possible to restore the true pixels in artifacts using pixels
located in artifacts-free regions. In each iteration, mNLM is performed on image
reconstructed by ART followed by positivity constraint. To solve the problem
caused by ART-mNLM that there is undesirable information that may appear in the
image, ART-TV is then utilized in the following iterative process after ART-mNLM
iterates for a number of iterations. The proposed algorithm is named as ART
mNLM/TV. RESULTS: Simulation experiments are performed to validate the
feasibility of algorithm. When the scanning range is [0, 150 degrees ], our
algorithm outperforms the ART-NLM and ART-TV with more than 40% and 29%
improvement in terms of SNR and with more than 58% and 49% reduction in terms of
MAE. Consistently, reconstructed images from real projection data also
demonstrate the effectiveness of presented algorithm. CONCLUSION: This paper uses
mNLM which benefits from redundancy of information across the whole image, to
recover the true value of pixels in artifacts region by utilizing pixels from
artifact-free regions, and artifacts around the edges can be mitigated
effectively. Experiments show that the proposed ART-mNLM/TV is able to achieve
better performances compared to traditional methods.
PMID- 27501876
TI - Molten thermoplastic dripping behavior induced by flame spread over wire
insulation under overload currents.
AB - The dripping behavior of the molten thermoplastic insulation of copper wire,
induced by flame spread under overload currents, was investigated for a better
understanding of energized electrical wire fires. Three types of sample wire,
with the same polyethylene insulation thickness and different core diameters,
were used in this study. First, overload current effects on the transient one
dimensional wire temperature profile were predicted using simplified theoretical
analysis; the heating process and equilibrium temperature were obtained. Second,
experiments on the melting characteristics were conducted in a laboratory
environment, including drop formation and frequency, falling speed, and
combustion on the steel base. Third, a relationship between molten mass loss and
volume variation was proposed to evaluate the dripping time and frequency. A
strong current was a prerequisite for the wire dripping behavior and the averaged
dripping frequency was found to be proportional to the square of the current
based on the theoretical and experimental results. Finally, the influence of
dripping behavior on the flame propagation along the energized electrical wire
was discussed. The flame width, bright flame height and flame spreading velocity
presented different behaviors.
PMID- 27501877
TI - Decolorization of azo dye by peroxymonosulfate activated by carbon nanotube:
Radical versus non-radical mechanism.
AB - Carbon nanotube (CNT) has been shown to effectively activate peroxymonosulfate
(PMS) to remove contaminants, whereas controversial activation mechanisms
(radical vs non-radical mechanism) were previously proposed. Here we report that
radical-induced decolorization of acid orange 7 (AO7) dominated in the CNT
activated PMS system, but non-radical mechanism was also involved at high Cl-
concentration. CNT exhibited high activity in activating PMS to decolorize AO7.
The decolorization rate of AO7 increased with increasing PMS dosages and CNT
loadings, rising temperature and higher pH. Radical quenching and
photoluminescence techniques confirmed the decolorization of AO7 in the CNT/PMS
system was caused by the radical oxidation, which dominantly took place on the
surface of CNT, rather than the bulk solution. The presence of Cl- exhibited a
dual effect on AO7 decolorization. Low concentration of Cl- slightly inhibited
AO7 decolorization, but further raising the concentration to above 0.1M
significantly accelerated its decolorizaition. Cl- was confirmed to react with
PMS to generate HClO, which effectively bleached AO7 through non-radical process
rather than radical process. The decolorization of AO7 induced from the non
radical process exhibited different degradation products and less mineralization
in comparison to that derived from radical process.
PMID- 27501878
TI - An Eco-tank system containing microbes and different aquatic plant species for
the bioremediation of N,N-dimethylformamide polluted river waters.
AB - An Eco-tank system of 10m was designed to simulate the natural river. It
consisted of five tanks sequentially connected containing microbes, biofilm
carriers and four species of floating aquatic plants. The purification
performance of the system for N,N-dimethylformamide (DMF) polluted river water
was evaluated by operating in continuous mode. DMF was completely removed in
Tanks 1 and 2 at influent DMF concentrations between 75.42 and 161.05mg L-1. The
NH4+-N concentration increased in Tank 1, followed by a gradual decrease in Tanks
2-5. Removal of NH4+-N was enhanced by aeration. The average effluent NH4+-N
concentration of Tank 5 decreased to a minimum of 0.89mg L-1, corresponding to a
decrease of 84.8% when compared with that before aeration. TN concentration did
not decrease significantly as expected after inoculation with denitrifying
bacteria. The average effluent TN concentration of the system was determined to
be 4.58mg L-1, still unable to satisfy the Class V standard for surface water
environmental quality. The results of this study demonstrated that the Eco-tank
system is an efficient process in removing DMF, TOC, and NH4+-N from DMF polluted
river water. However, if possible, alternative technologies should be adopted for
controlling the effluent TN concentration.
PMID- 27501879
TI - pH-dependent degradation of p-nitrophenol by sulfidated nanoscale zerovalent iron
under aerobic or anoxic conditions.
AB - Sulfidated nanoscale zerovalent iron (S-NZVI) is attracting considerable
attention due to its easy production and high reactivity to pollutants. We
studied the reactivity of optimized S-NZVI (Fe/S molar ratio 6.9), comparing with
pristine nanoscale zerovalent iron (NZVI), at various pH solutions (6.77-9.11)
towards p-nitrophenol (PNP) under aerobic and anoxic conditions. Studies showed
that the optimized extent of sulfidation could utterly enhance PNP degradation
compared to NZVI. Batch experiments indicated that in anoxic S-NZVI systems the
degradation rate constant increased with increasing pH up to 7.60, and then
declined. However, in aerobic S-NZVI, and in anoxic or aerobic NZVI systems, it
decreased as pH increased. It was manifested that anoxic S-NZVI systems preferred
to weaker alkaline solutions, whereas aerobic S-NZVI systems performed better in
acidic solutions. The highest TOC removal efficiency of PNP (17.59%) was achieved
in the aerobic S-NZVI system at pH 6.77, revealing that oxygen improved the
degradation of PNP by excessive amounts of hydroxyl radicals in slightly acidic
conditions, and the TOC removal efficiency was supposed to be further improved in
moderate acidic solutions. Acetic acid, a nontoxic ring opening by-product,
confirms that the S-NZVI system could be a promising process for industrial
wastewater containing sulfide ions.
PMID- 27501880
TI - Integrated biodepuration of pesticide-contaminated wastewaters from the fruit
packaging industry using biobeds: Bioaugmentation, risk assessment and optimized
management.
AB - Wastewaters from fruit-packaging plants contain high loads of toxic and
persistent pesticides and should be treated on site. We evaluated the depuration
performance of five pilot biobeds against those effluents. In addition we tested
bioaugmentation with bacterial inocula as a strategy for optimization of their
depuration capacity. Finally we determined the composition and functional
dynamics of the microbial community via q-PCR. Practical issues were also
addressed including the risk associated with the direct environmental disposal of
biobed-treated effluents and decontamination methods for the spent packing
material. Biobeds showed high depuration capacity (>99.5%) against all pesticides
with bioaugmentation maximizing their depuration performance against the
persistent fungicide thiabendazole (TBZ). This was followed by a significant
increase in the abundance of bacteria, fungi and of catabolic genes of aromatic
compounds catA and pcaH. Bioaugmentation was the most potent decontamination
method for spent packing material with composting being an effective alternative.
Risk assessment based on practical scenarios (pome and citrus fruit-packaging
plants) and the depuration performance of the pilot biobeds showed that discharge
of the treated effluents into an 0.1-ha disposal site did not entail an
environmental risk, except for TBZ-containing effluents where a larger disposal
area (0.2ha) or bioaugmentation alleviated the risk.
PMID- 27501881
TI - Morphology and concentration of smoke from fluorinated ethylene propylene wire
insulation in microgravity under forced airflow.
AB - The production of smoke particles from the jet bursting flame caused by
overheating fluorinated ethylene propylene (FEP) wire insulations was
investigated. Experiments examining the morphology and volume fraction of the
fractal smoke particle aggregates with forced airflow were conducted in a 3.5s
drop tower. Gravity level and forced flow were shown to have significant
hydrodynamic effects on the pathlines and fractal aggregation of the smoke
particles, thus the residence time-dependent flame shape, particle size and
concentration have obvious changes. For cases in still air, compared with normal
gravity, the jet flame in microgravity has a spherical shape, the mean primary
particle and aggregate gyration radius are bigger due to longer residence time,
but the fractal dimension maintains at about 1.79, similar to that in the normal
gravity level; the calculated smoke volume fraction is also bigger. For cases
with force flow in microgravity, the mean primary particle diameter, the mean
aggregate gyration radius, and soot volume fraction all decrease with increasing
forced flow due to decreasing residence time.
PMID- 27501882
TI - Coupling electrokinetics with microbial biodegradation enhances the removal of
cycloparaffinic hydrocarbons in soils.
AB - An innovative approach that couples electrokinetics with microbial degradation to
breakdown cycloparaffinic hydrocarbons in soils is described. Soils were spiked
with cyclododecane, used as a model pollutant, at approximately 1000mgkg-1. A
mixture of petroleum-utilizing bacteria was added to achieve about 106-107 CFUg
1. Then, three treatments were applied for 25 days: (1) no electric field,
control; (2) a constant voltage gradient of 1.3Vcm-1 in one direction; and (3)
the same electric field, but with periodical switching of polarity. The
degradation pathway of cyclododecane was not changed by the electric field, but
the dynamic processes were remarkably enhanced, especially when the electric
field was periodically switched. After 25 days, 79.9% and 87.0% of the
cyclododecane was degraded in tests 2 and 3, respectively; both much higher than
the 61.5% degraded in test 1. Analysis of the intermediate products strongly
indicated that the competitive advantage of the electric field was the increase
in ring-breaking of cyclododecane, resulting in greater concentrations of linear
substances that were more susceptible to microbial attack, that is, beta
oxidation. The conditions near the cathode were more favorable for the growth and
metabolism of microorganisms, which also enhanced beta-oxidation of the linear
alkanoic acids. Therefore, when the electric field polarity was periodically
switched, the functions of both the anode and cathode electrodes were applied
across the whole soil cell, further increasing the degradation efficiency.
PMID- 27501883
TI - Simultaneous biological-photocatalytic treatment with strain CDS-8 and TiO2 for
chlorothalonil removal from liquid and soil.
AB - In this study, a novel chlorothalonil (CTN) degrading bacterial strain CDS-8,
identified as Pseudomonas sp., was combined with photocatalyst titanium dioxide
(TiO2) for the CTN degradation in liquid and soil. After 7day incubation, 90.73%
of CTN was removed from mineral salt medium (MSM) by CDS-8 with the optimal
condition at pH 7.0 and 30 degrees C. Single biodegradation or photocatalytic
degradation could not degrade CTN completely, and many toxic and persistent
intermediate metabolites remained. However, simultaneous biological
photocatalytic treatments could markedly remove CTN and reduce the chemical
oxygen demand (COD) which could not be removed by single biodegradation or
photocatalytic degradation. In MSM, treatment with CDS-8/40mgL-1 TiO2 showed the
highest COD removal rate (84.10%). Furthermore, combined CDS-8/TiO2 treatments
could effectively degrade CTN in soil. In treatments with CDS-8/20mgkg-1 TiO2 of
soil, the maximum CTN removal rate reached 97.55% in turned soils. However, with
CDS-8/40mgkg-1 TiO2 of soil, the maximum CTN removal rate (94.94%) was found in
static soil. In general, the combined biological-photocatalytic treatments
provided a promising alternative candidate for the remediation of CTN
contaminated sites.
PMID- 27501884
TI - Assessment of the parenchymal blood volume by C-arm computed tomography for
radioembolization dosimetry.
AB - PURPOSE: Aim of the study was to evaluate the impact of parenchymal blood volume
(PBV) C-arm CT in transarterial radioembolization (TARE) planning procedure
regarding the appropriateness of segmental blood supply from selective catheter
positions defined by angiographic images compared to PBV mapsto determine the
influence of changed target volumes on dose calculation. MATERIAL AND METHODS: A
total of 22 consecutive patients (median age, 62 years) underwent a TARE planning
procedure were included in this retrospective study. Selective angiograms and
selective PBV C-arm CT (right and left liver lobe) were evaluated in a blinded
fashion, regarding segmental hepatic artery variants. Volumetry of target volume
and dosimetry of glass and resin microspheres were performed. RESULTS:
Classification of segment IV and segment I to the corresponding target vascular
bed supply was correct in 91.0% (20/22) and 86.4% (19/22) for angiography and C
arm CT, respectively. Except one case, all other liver segments were classified
properly to the left and right hepatic arterial supply. Based on the mismatch of
the angiographic and the C-arm CT approach, changes of target volume were evident
in 27.3% of patients, resulting in a mean mismatch volume of 90+/-54ml (range, 51
198ml) and a percentage of dose differences of 14.2+/-11.8% and 12.6+/-10.6% for
the right and 12.5+/-8.5% and 11.1+/-7.8% for the left liver lobe in glass and
resin microspheres, respectively. CONCLUSION: The C-arm CT approach is superior
to the angiographic determination of vascular supply of specific liver segments
for dosimetry before radioembolization. Especially for unexperienced
interventional radiologists or for a complex anatomy, C-arm CT improves
individualized dosimetry concepts.
PMID- 27501885
TI - First pass perfusion imaging to improve the assessment of left ventricular
thrombus following a myocardial infarction.
AB - PURPOSE: To assess whether a first-pass perfusion sequence (FPP) improved the
detection of left ventricular thrombus (LVT). MATERIALS AND METHODS: Three
hundred and twenty-nine patients with a first STEMI were prospectively included
to undergo cardiac magnetic resonance (CMR) at baseline and after a 3-month
follow-up. A CMR delayed analysis was performed by three blinded examiners (2 CMR
experts and 1 novice) according to a two-step reading protocol. First, an
analysis was performed on cine CMR and late gadolinium enhancement (routine
stage). Then, the FPP stage was performed following initial protocol along with a
FPP sequence. RESULTS: LVT was found in 31 out of a total of 638 (4.9%) CMR
scans, affecting 30 (9.1%) individuals. All were located in the left ventricular
apex. The FPP stage improved significantly the LVT diagnosis for all readers, in
10 and 13 cases (32% and 42%) of LVT suspicion for the experts and 16 cases (41%)
for the novice. Respectively 1, 2 and 6 LVT were not detected during the routine
stage by the CMR experts and the novice. For the novice, the FPP stage improved
diagnosis sensitivity from 78.1 to 91.2%. CONCLUSIONS: The prevalence of LVT
following a myocardial infarction reached 9.1% and increased with the reading of
FPP sequence. The FPP stage improved expert diagnostic certitude and the novice's
abilities to reach expert level.
PMID- 27501886
TI - Diffusion tensor imaging of the hippocampus in chronic cigarette smokers.
AB - PURPOSE: Previous studies have demonstrated neuronal dis-integrity in chronic
smokers using diffusion tensor imaging (DTI). However, assessment of hippocampal
DTI has not been performed in this group. The purpose of this study was to
investigate the hippocampal integrity in chronic smokers and non-smokers and to
compare this to memory performance. METHODS: We used in vivo DTI to measure the
differences in hippocampal integrity between 88 chronic smoker and 88 non-smoking
subjects. DTI was performed on a 3T scanner. We administered a verbal learning
test to assess new verbal learning capabilities. The immediate recall (IR) was
administered immediately after test procedure and delayed recall (DR) after
15min. RESULTS: Mean values of fractional anisotropy (FA) for non-smokers and
smokers were 0.46 and 0.40, respectively (p<0.05). Mean IR word number for non
smokers and smokers was 11.6, 9.04, respectively (p<0.05). The mean word number
of DR for non-smokers and smokers was 10.2, 7.2, respectively (p<0.05).
CONCLUSIONS: This is the first study of hippocampal DTI assessment in the chronic
smokers. We found that decreased hippocampal FA associated with neuronal dis
integrity and worse memory performance in chronic smokers than non-smokers. We
also found a low positive correlation hippocampal FA values with memory
performance in nonsmoking group.
PMID- 27501887
TI - Comparison between dynamic susceptibility contrast magnetic resonance imaging and
arterial spin labeling techniques in distinguishing malignant from benign brain
tumors.
AB - OBJECTIVES: The purpose of this study was to preliminarily compare unenhanced
arterial spin-labeled (ASL) imaging, dynamic susceptibility contrast-enhanced
cerebral blood volume (DSCE-CBV) magnetic resonance imaging (MRI) for evaluation
of tumor perfusion in patients with brain tumors. MATERIALS AND METHODS: A total
of 27 patients with brain tumors were examined in 1,5T MRI. Single phase and
multiphase ASL, DSCE-CBV examinations were assessed by both qualitative and
quantitative analysis for the detection of malignancy. Imaging results were
correlated with a histopathology or follow-up. RESULTS: Based on 31 studies in 27
patients with brain tumors, the visual inspection sensitivities for ASL and
dynamic DSC perfusion imaging were 88% and 94%, respectively, with 100%
specificity for both. On qualitative evaluation, sensitivities for ASL and DSC
perfusion imaging perfusions were 88% and 94%, respectively, with 100%
specificity for both. The highest sensitivity values for quantitative ASL imaging
were obtained using a normalized cut-off ratio of 1.65, resulting in sensitivity
of 94% for ASL imaging and cut-off ratio of 1.95 and sensitivity 94% for DSCE-CBV
imaging. CONCLUSION: The present study revealed similar sensitivity and
specificity for both multhiphase ASL and DSC MRI. Thus, we suggest that ASL
perfusion can be used in daily clinical practice.
PMID- 27501888
TI - Adding 3D automated breast ultrasound to mammography screening in women with
heterogeneously and extremely dense breasts: Report from a hospital-based, high
volume, single-center breast cancer screening program.
AB - PURPOSE: The aim of this study was to evaluate the impact of the 3D automated
breast ultrasound (3D ABUS) when added to full field digital screening
mammography (FFDSM), on breast cancer detection and recall rates in asymptomatic
women with dense breasts examined in a high-volume breast cancer screening
mammography center. METHODS AND MATERIAL: 1668 asymptomatic women, age 40-74
years, with heterogeneously dense parenchyma (ACR3) or extremely dense breast
(ACR4) were included in the study. FFDSM was performed using standard
craniocaudal (CC) and mediolateral oblique (MLO) views followed by
anteroposterior (AP); lateral (LAT) and medial (MED) acquisitions of 3D ABUS in
both breasts. All mammograms were double read by two dedicated breast
radiologists. The 3D ABUS was read by the first radiologist immediately after
reading the mammograms. The second reader looked at the 3D ABUS only if there was
a need for consensus discussion because of unclear or abnormal mammograms or 3D
ABUS. RESULTS: The combined FFDSM and 3D ABUS generated a total of 6.6 cancers
per 1000 women screened (95% CI: 3.0, 10.2; p<0.001) compared with 4.2 cancers
per 1000 women screened (95% CI) for FFDSM alone. The difference in yield was an
additional 2.4 detected cancers per 1000 women screened (95% CI: 0.6, 4.8;
p<0.001). The corresponding recall rate per 1000 women screened was 13.8 (95% CI:
9.0, 19.8) for FFDSM alone and 22.8 for combined FFDSM and ABUS (95% CI: 16.2,
30.0), yielding a difference of an additional 9.0 recalls per 1000 women screened
(95% CI: 3.0, 15.0; p=0.004). CONCLUSION: The addition of 3D ABUS to FFDSM in
women with ACR3 or ACR4 breast density significantly improved invasive breast
cancer detection rate with an acceptable recall increase.
PMID- 27501889
TI - Changes in brain magnetic resonance imaging patterns for preterm infants after
introduction of a magnetic resonance-compatible incubator coil system: 5-year
experience at a single institution.
AB - OBJECTIVE: To evaluate the changes in using patterns of brain magnetic resonance
imaging (MRI) in preterm infants after introduction of a MR-compatible incubator
coil system. MATERIALS AND METHODS: Brain MRIs for preterm infants with the MR
compatible incubator coil from March 2010 to July 2014 (n=154, group A) were
compared with MRIs prior to the introduction of the incubator coil, from March
2005 to February 2010 (n=65, group B). Clinical data, MRI findings, acquisition
time, and incidence of adverse events during the study were retrospectively
reviewed. For the qualitative analysis of the examinations, the presence of
motion artefact, spatial resolution, and overall image quality were assessed.
Signal uniformity of each sequence was evaluated for a quantitative comparison.
RESULTS: Comparing with group B, Group A was significantly younger (36+3 vs. 38+3
weeks, p<0.001), had a significantly lower body weight (2006.6 and 2390.3g
respectively; p<0.001) at the time of MRI, and had shorter time interval (54.3+/
2.6 vs. 70.5+/-4.4days, p=0.002) between birth and examination. Abnormal findings
were noted more frequently in group A (n=100, 65%) than in B (n=24, 37%. p=0.001)
with a significantly higher incidence of diffusion restriction (n=21, 13.6% vs.
n=4, 6.2%, p=0.034). Mean image acquisition time was significantly shorter in
group A (21.4+/-4.5 vs. 25.4+/-5.5min, p<0.001) with significant lower adverse
events during MRI (n=26, 40 vs. n=6, 3.9%, p<0.001). Group A exhibited
significantly less motion artefact, better spatial resolution, and better overall
image quality with decreased signal variation than group B (all p<0.001).
CONCLUSION: Application of the MR-compatible incubator for preterm brain MRI
evaluation is safer and provides more timely evaluation of preterm infants with
better image quality.
PMID- 27501890
TI - Reducing CT radiation exposure with organ effective modulation: A retrospective
clinical study.
AB - OBJECTIVE: To evaluate the effect of Organ Effective Modulation (OEM) on
objective and subjective image quality as well as the radiation dose needed for
thoracoabdominal computed tomography (CT). METHOD: This retrospective study
included 196 consecutive patients who were referred to our institution for
enhanced thoracoabdominal CT on a specific scanner. Patients were divided into
two groups: those for whom OEM was used and those for whom it was not used. For
the non-OEM group, the tube current was controlled with an angular-longitudinal
modulation technique. All CT examinations were performed with adaptive iterative
dose reduction with 3D processing (AIDR-3D). The radiation dose was compared
between the two groups. Objective image noise was measured in several regions at
the thoracic and abdominal level. Subjective image quality was assessed by two
radiologists for image noise, artifacts, sharpness, and overall diagnostic
acceptability at the chest, abdomen, and pelvis. RESULTS: The CTDIvol was 8.3%
lower in the OEM group and high-BMI patients tended to have higher dose
reductions. Image noise was not significantly different at the thoracic level,
except for the ventral air space, which showed more noise in the OEM group. At
the abdominal level, the OEM group showed less noise in every region, only
demonstrating a significant difference in the posterior segment of the right
hepatic lobe. Subjective image quality assessment indicated more artifacts in the
thoracic ventral air space in the OEM group, whereas all other items including
the overall diagnostic acceptability showed no statistical differences between
the two groups. CONCLUSION: OEM can reduce the radiation dose by approximately 8%
without affecting the diagnostic acceptability of the image compared to angular
longitudinal modulation, especially in patients with a high BMI.
PMID- 27501891
TI - Dual-energy CT to estimate clinical severity of chronic thromboembolic pulmonary
hypertension: Comparison with invasive right heart catheterization.
AB - PURPOSE: To evaluate whether the extent of perfusion defects assessed by
examining lung perfused blood volume (PBV) images is a stronger estimator of the
clinical severity of chronic thromboembolic pulmonary hypertension (CTEPH)
compared with other computed tomography (CT) findings and noninvasive parameters.
MATERIALS AND METHODS: We analyzed 46 consecutive patients (10 men, 36 women)
with CTEPH who underwent both dual-energy CT and right-heart catheter (RHC)
examinations. Lung PBV images were acquired using a second-generation dual-source
CT scanner. Two radiologists independently scored the extent of perfusion defects
in each lung segment employing the following criteria: 0, no defect, 1, defect in
<50% of a segment, 2, defect in >=50% of a segment. Each lung PBV score was
defined as the sum of the scores of 18 segments. In addition, all of the
following were recorded: 6-min walk distance (6MWD), brain natriuretic peptide
(BNP) level, and RHC hemodynamic parameters including pulmonary artery pressure
(PAP), right ventricular pressure (RVP), cardiac output (CO), the cardiac index
(CI), and pulmonary vascular resistance (PVR). Bootstrapped weighted kappa values
with 95% confidence intervals (CIs) were calculated to evaluate the level of
interobserver agreement. Correlations between lung PBV scores and other
parameters were evaluated by calculating Spearman's rho correlation coefficients.
Multivariable linear regression analyses (using a stepwise method) were employed
to identify useful estimators of mean PAP and PVR among CT, BNP, and 6MWD
parameters. A p value<0.05 was considered to reflect statistical significance.
RESULTS: Interobserver agreement in terms of the scoring of perfusion defects was
excellent (kappa=0.88, 95% CIs: 0.85, 0.91). The lung PBV score was significantly
correlated with the PAP (mean, rho=0.48; systolic, rho=0.47; diastolic,
rho=0.39), PVR (rho=0.47), and RVP (rho=0.48) (all p values<0.01). Multivariable
linear regression analyses showed that only the lung PBV score was significantly
associated with both the mean PAP (coefficient, 0.84, p<0.01) and the PVR
(coefficient, 28.83, p<0.01). CONCLUSION: The lung PBV score is a useful and
noninvasive estimator of clinical CTEPH severity, especially in comparison with
the mean PAP and PVR, which currently serve as the gold standards for the
management of CTEPH .
PMID- 27501892
TI - Decrease of pulmonary blood flow detected by phase contrast MRI is correlated
with a decrease in lung volume and increase of lung fibrosis area determined by
computed tomography in interstitial lung disease.
AB - PURPOSE: Lung volume and pulmonary blood flow decrease in patients with
interstitial lung disease (ILD). The purpose of this study was to assess the
relationship between pulmonary blood flow and lung volume in ILD patients.
METHODS: This research was approved by the institutional review board. Twenty
seven patients (9 men, 18 women; mean age, 59 years; range, 24-79 years) with ILD
were included. Blood flow was assessed in the pulmonary trunk and the left and
right pulmonary arteries by phase contrast magnetic resonance imaging (MRI). Lung
volume and the computed tomography (CT) visual score that indicates the severity
of ILD were assessed on the left and right sides by thin-section CT scanning.
Lung volume was automatically measured by lung analysis software (VINCENT Ver.
4). The CT visual score was measured by averaging the proportion of abnormal lung
area at five anatomic levels. Pearson's correlation coefficient was used to
determine the relationship between pulmonary blood flow and lung volume. RESULTS:
Pulmonary blood flow showed a significant correlation with lung volume (both:
r=0.52, p=0.006; left: r=0.61, p=0.001; right: r=0.54, p=0.004) and CT visual
score (both: r=-0.39, p=0.04; left: r=-0.48, p=0.01; right: r=-0.38, p=0.04).
Partial correlation analysis, controlled for age, height and weight, showed a
significant correlation between pulmonary blood flow and lung volume (both:
r=0.43, p=0.03; left: r=0.55, p=0.005; right: r=0.48, p=0.01) and CT visual score
(both: r=-0.58, p=0.003; left: r=-0.51, p=0.01; right: r=-0.64, p=0.001).
CONCLUSION: In ILD, reduced pulmonary blood flow is associated with reduced lung
volume and increased abnormal lung area.
PMID- 27501893
TI - Shear wave elastography and parathyroid adenoma: A new tool for diagnosing
parathyroid adenomas.
AB - OBJECTIVES: This study prospectively determines the shear wave elastography
characteristics of parathyroid adenomas using virtual touch imaging
quantification, a non-invasive ultrasound based shear wave elastography method.
METHODS: This prospective study examined 57 consecutive patients with
biochemically proven primary hyperparathyroidism and solitary parathyroid adenoma
identified by ultrasound and confirmed by at least one of the following: surgical
resection, positive Technetium-99m Sestamibi Scintigraphy (MIBI) scan, or fine
needle aspiration biopsy with positive PTH washout (performed only in MIBI
negative patients). Vascularity and shear wave elastography were performed for
all patients. Parathyroid adenoma stiffness was measured as shear wave velocity
in meters per second. RESULTS: The median (range) pre-surgical value for PTH and
calcium were 58pg/mL (19, 427) and 10.8mg/dL (9.5, 12.1), respectively. 37
patients had positive MIBI scan. 20 patients had negative MIBI scan but diagnosis
was confirmed with positive PTH washout. 42 patients underwent parathyroidectomy,
and an adenoma was confirmed in all. The median (range) shear wave velocity for
all parathyroid adenomas enrolled in this study was 2.02m/s (1.53, 2.50). The
median (range) shear wave velocity for thyroid tissue was 2.77m/s (1.89, 3.70).
The shear wave velocity of the adenomas was independent of adenoma size, serum
parathyroid hormone concentration, or plasma parathyroid hormone concentration.
CONCLUSIONS: Tissue elasticity of parathyroid adenoma is significantly lower than
thyroid tissue. B-mode features and distinct vascularity pattern are helpful
tools in diagnosing parathyroid adenoma with ultrasound. Shear wave elastography
may provide valuable information in diagnosing parathyroid adenoma.
PMID- 27501894
TI - Pleural irregularities and mediastinal pleural involvement in early stages of
malignant pleural mesothelioma and benign asbestos pleural effusion.
AB - OBJECTIVE: To elucidate differences in the level and localization of pleural
irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos
pleural effusion (BAPE) using CT. STUDY DESIGN: Retrospective assessment of CT
findings of consecutive patients with BAPE at a single centre and patients with
eMPM reported in Japanese vital statistics. METHODOLOGY: Thirty-six patients with
confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of
eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans,
and clinical and pathologic details were obtained for all patients and were
reviewed by one radiologist, two pathologists, and two pulmonologists.
Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening
were assessed in all patients. RESULTS: Prevalence of asbestosis, pleural plaque,
rounded atelectasis, and diffuse pleural thickening was significantly higher in
the BAPE group. Low-level irregularity was more common in the BAPE group
(p<0.001), whereas high-level irregularity, mediastinal localization, and
interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar
pleural irregularity was not observed in any patients in the BAPE group, although
55% of patients in the eMPM group showed interlobar pleural irregularity.
Mediastinal pleural involvement was observed in 74% of patients in the eMPM group
and had a positive predictive value of 89%. CONCLUSION: This study demonstrates
that the level and localization of plural irregularities significantly differed
between patients with BAPE and eMPM. Large-scale prospective studies are needed
to fully establish the diagnostic utility of such differences.
PMID- 27501895
TI - Morphologic and functional abnormalities in patients with Ebstein's anomaly with
cardiac magnetic resonance imaging: Correlation with tricuspid regurgitation.
AB - PURPOSE: The aim of this study was to assess the correlations of functional and
dimensional parameters with the severity of tricuspid regurgitation in patients
with Ebstein's anomaly (EA) by using cardiac magnetic resonance (CMR) imaging.
MATERIALS AND METHODS: Thirty-three patients with EA without previous cardiac
surgery and 25 normal individuals were recruited and underwent both cardiac MR
imaging and preoperative transthoracic echocardiography. The left ventricular
(LV) functional parameters and dimensions of the right ventricle (RV) and LV were
measured using 3.0-T cardiac MR imaging. Tricuspid regurgitation severity grading
was estimated by echocardiography. The functional and dimensional parameters were
compared between EA patients and controls using independent sample t-tests.
Spearman's rank correlation was used to determine the correlations between the
functional and dimensional parameters and tricuspid regurgitation. Receiver
operating characteristic (ROC) analysis was used to predict tricuspid
regurgitation severity using individual functional and dimensional parameters.
RESULTS: Statistical analysis revealed significant differences in the functional
and dimensional parameters between EA patients and controls. Within the EA group,
tricuspid valve regurgitation negatively correlated well with the left
ventricular ejection fraction (LVEF) (r=-0.558, p=0.001). The ratio of the right
ventricular (functional right ventricle) end-diastolic dimension to the left
ventricle end-diastolic dimension (RVEDD/LVEDD) in EA patients also correlated
well with the severity of tricuspid valve regurgitation (r=0.492, p=0.004).
Moreover, ROC analysis revealed that high sensitivity and specificity were
obtained for predicting the severity of tricuspid valve regurgitation with LVEF
(78.3%, 90.0%) and RVEDD/LVEDD (78.3%, 94.3%). CONCLUSION: In EA patients, the
left and right ventricular functional and dimensional parameters from MRI
correlated well with tricuspid regurgitation, which helped predict the severity
of EA.
PMID- 27501896
TI - Quantification of lung perfusion blood volume (lung PBV) by dual-energy CT in
patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and
after balloon pulmonary angioplasty (BPA): Preliminary results.
AB - OBJECTIVES: Balloon pulmonary angioplasty (BPA) is a treatment option for
patients with chronic thromboembolic pulmonary hypertension (CTEPH). Its effect
on pulmonary perfusion has not been quantified; we examined the clinical
significance of pulmonary blood volume (PBV) using dual-energy computed
tomography (DECT) in patients with CTEPH undergoing BPA. METHODS: In this
retrospective study of 16 BPAs in eight female patients with CTEPH, we evaluated
both-lung (n=16), right- or left-lung (n=32), and three right- or left-segment
(upper, middle, and lower) (n=96) PBVs before and after BPA, using DECT. We
evaluated the relationships between improvement in lung PBV and pulmonary artery
(PA) pressure (PAP), cardiac index (CI), pulmonary vascular resistance (PVR), and
6-min walking distance. We measured PA enhancement (PAenh) on DECT images and
calculated lung PBV/PAenh to adjust timing. RESULTS: Pre- and post-BPA 6-segment
lung PBV/PAenh were 0.067+/-0.021 and 0.077+/-0.019, respectively, in the treated
segment (p<0.0001). There were significant positive correlations between pre- to
post-BPA improvements in both-lung PBV/PAenh and PAP (R=0.69, p=0.005), PVR
(R=0.56, p=0.03), and 6-min walking distance (R=0.67, p=0.01). CONCLUSIONS:
Improved PBV after BPA, reflecting increased lung perfusion, was positively
correlated with PAP, PVR, and 6-min walking distance. Lung PBV may be an
indicator of BPA treatment effect.
PMID- 27501897
TI - Automatic segmentation of abdominal organs and adipose tissue compartments in
water-fat MRI: Application to weight-loss in obesity.
AB - PURPOSE: To develop a fully automatic algorithm for abdominal organs and adipose
tissue compartments segmentation and to assess organ and adipose tissue volume
changes in longitudinal water-fat magnetic resonance imaging (MRI) data.
MATERIALS AND METHODS: Axial two-point Dixon images were acquired in 20 obese
women (age range 24-65, BMI 34.9+/-3.8kg/m(2)) before and after a four-week
calorie restriction. Abdominal organs, subcutaneous adipose tissue (SAT)
compartments (abdominal, anterior, posterior), SAT regions along the feet-head
direction and regional visceral adipose tissue (VAT) were assessed by a fully
automatic algorithm using morphological operations and a multi-atlas-based
segmentation method. RESULTS: The accuracy of organ segmentation represented by
Dice coefficients ranged from 0.672+/-0.155 for the pancreas to 0.943+/-0.023 for
the liver. Abdominal SAT changes were significantly greater in the posterior than
the anterior SAT compartment (-11.4%+/-5.1% versus -9.5%+/-6.3%, p<0.001). The
loss of VAT that was not located around any organ (-16.1%+/-8.9%) was
significantly greater than the loss of VAT 5cm around liver, left and right
kidney, spleen, and pancreas (p<0.05). CONCLUSION: The presented fully automatic
algorithm showed good performance in abdominal adipose tissue and organ
segmentation, and allowed the detection of SAT and VAT subcompartments changes
during weight loss.
PMID- 27501898
TI - Pancreatic cysts: What imaging characteristics are associated with development of
pancreatic ductal adenocarcinoma?
AB - PURPOSE: To assess relationship between pancreatic cysts (PC) and pancreatic
ductal adenocarcinoma (PDAC) and to compare imaging features of PC in subjects
who develop PDAC and those who do not. MATERIAL AND METHODS: This case-control
IRB-approved HIPAA-compliant study included patients with PDAC (cases) and lung
cancer (controls), diagnosed between 1/1/05-1/1/14. The most recent abdominal
CT/MR of each patient done >6months prior to cancer diagnosis date was reviewed
by radiologist blinded to case/control status. Presence of PC, number and size of
largest PC, presence of main pancreatic duct (MPD) dilatation (MPD >3mm) were
recorded. Simple PC was defined as lack of calcifications, septations and
enhancement. Logistic regression models with binary outcome of PDAC were
constructed. RESULTS: There were 88 cases and 273 controls with mean ages of 69.6
years (+/-10.3) and 69.8 years (+/-12.0), respectively (p=0.864). PC were present
in 21.6% (19/88) cases and in 9.2% (25/273) controls (p=0.002). The OR of PC for
development of PDAC was 2.83, adjusting for age, sex and race (p=0.001). Mean PC
size was 14.8mm (+/-8.7) in cases and 7.6mm (+/-8.0) in controls (p=0.007). PC
were solitary in 6 (31.6%) of 19 cases and 21 (84.0%) of 25 controls (p=0.001).
There was no significant difference in proportions of simple cysts or MPD
dilatation between cases and controls. Multiple PC had 8.2 times increased odds
of PDAC compared with solitary PC, adjusting for cyst size (p=0.007). CONCLUSION:
Multiple PC are associated with 8.2 times higher odds of PDAC compared with
solitary PC.
PMID- 27501899
TI - Radiation exposure levels of routine SPECT/CT imaging protocols.
AB - AIMS: To assess incremental and total patient exposure from clinical SPECT/CT
imaging by means of effective dose estimations with regards to different
protocols and SPECT/CT systems. MATERIALS AND METHODS: Consecutive patient
exposure levels were documented prospectively from SPECT/CT operations at three
European imaging centers. Documentation included the volume-weighted computed
tomography (CT) dose index, the CT dose length product (DLP) and the amount of
applied radiopharmaceutical. SPECT/CT examinations were categorized regionally
into head, neck, myocardium, thorax, abdomen, extremities and whole-body.
Effective dose from the CT (EDCT) was estimated from the DLP using gender
specific conversion factors. EDSPECT was estimated from the injected activity
levels and corresponding conversion factors (ICRP 106). RESULTS: This study
included 678 SPECT/CT examinations. EDCT per indication and EDSPECT per tracer
ranged from 0.01mSv to 7.4mSv and from 1.1mSv to 12.2mSv, respectively. In
general, EDSPECT contributed most to overall patient exposure. Total EDSPECT/CT
averaged across all protocol categories was 6.7mSv. CONCLUSION: Total patient
exposure from clinical SPECT/CT is 7mSv on average. Individual dose levels vary
with the clinical indication and on-site protocol parameters.
PMID- 27501900
TI - Value of ultra-low-dose chest CT with iterative reconstruction for selected
emergency room patients with acute dyspnea.
AB - OBJECTIVE: To compare the diagnostic confidence between low-dose computed
tomography (LDCT) and ultra-low-dose CT (ULDCT) of the chest on a single source
CT system (SSCT) for patients with acute dyspnoea. MATERIALS AND METHODS: One
hundred thirty-three consecutive dyspnoeic patients referred from the emergency
room (ER) were selected to undergo two sequential non-enhanced chest CT
acquisitions: LDCT first acquisition (100kVp and 60mAs), followed by ULDCT
(100kVp+/-20 and 10mAs). Images were reconstructed with sinogram affirmed
reconstruction (SAFIRE). Objective and subjective image quality assessments were
made. Two radiologists evaluated subjective image quality and the level of
diagnostic confidence as certain or uncertain. RESULTS: The mean effective doses
(ED) were 1.164+/-0.403 and 0.182+/-0.028mSv for LDCT and ULDCT, respectively.
Objective image quality improved significantly on lung images of ULDCT compared
with LDCT (p<0.05). Subjective image quality was rated excellent/good in 90% of
patients with BMI=25kg/m(2) for ULDCT. The level of diagnostic confidence was
"certain" in all cases for both radiologists with excellent inter-observer
agreement (k=1). CONCLUSION: Chest ULDCT with SAFIRE on a SSCT allows a high
level diagnostic confidence for the evaluation of selected acute dyspnoeic
patients.
PMID- 27501901
TI - Does motion affect liver stiffness estimates in shear wave elastography? Phantom
and clinical study.
AB - This study was undertaken to evaluate the impact of free-breathing (FB) vs. Apnea
on Shear-wave elastography (SWE) measurements. Quantitative liver-stiffness
measurements were obtained during FB and Apnea for 97 patients with various body
morphologies and liver textures. Quality indexes of FB and Apnea elasticity maps
(percentage of non-filling (PNF), temporal (TV) and spatial (SV) variabilities)
were computed. SWE measurements were also obtained from an homogeneous phantom at
rest and during a mechanically-induced motion. Liver-stiffness values estimated
from FB and Apnea acquisitions were correlated, particularly for homogeneous
livers (r=0.76, P<0.001) and favorable body-morphologies (r=0.68, P<0.001).
However FB values were consistently 20-25% lower than Apnea ones (P<0.001). FB
also systematically resulted in degradation of TV (P<0.005) and PNF (P<0.001)
compared to Apnea but had no impact on SV. With the phantom, no differences
between SWE measurements at rest and during motion were observed. Apnea and FB
measurements are highly correlated, although FB data quality is degraded compared
to Apnea and estimated stiffness in FB is systematically lower than in Apnea.
These discrepancies between rest and motion states were observed for patients but
not for phantom data, suggesting that patient breath-holding impacts liver
stiffness.
PMID- 27501902
TI - Quantitative apparent diffusion coefficient measurement obtained by 3.0Tesla MRI
as a potential noninvasive marker of tumor aggressiveness in breast cancer.
AB - PURPOSE: To assess the association between apparent diffusion coefficient (ADC),
and histological prognostic parameters in malignant breast lesions. The ability
of ADC to identify lesions with the presence of Lymphovascular invasion (LVI) in
breast carcinoma was also examined. MATERIALS AND METHODS: This HIPAA-compliant
retrospective study consisted of 212 consecutive patients with known cancers who
underwent 3.0T MRI between January 2011 and 2013. In this study, a total of 126
malignant lesions in 114 women, who had undergone DWI (b-values of 0 and
1000s/mm(2)) in addition to diagnostic MRI, were included. Patients with less
than 0.8cm lesions, or those who underwent neoadjuvant chemotherapy or suboptimal
DW images were excluded. Classical prognostic factors [lesion size,
histopathological type and grade, lymph node (LN) status and lymphovascular
invasion (LVI)], molecular prognostic markers [estrogen receptor (ER),
progesterone receptor (PR) and human epidermal grow factor receptor 2 (HER2)]
were reviewed and recorded. A region of interest (ROI) was drawn within the
lesions to measure ADC values. Statistical analyses were performed by the
Wilcoxon rank sum test (statistical significance at P<0.05). Adjusted p values
from multiple comparison analysis were also calculated. RESULTS: This study
demonstrates an inverse correlation between ADC and LVI in malignant lesions and
the ability of ADC to identify aggressiveness in lesions with positive LVI. Tumor
size, grade, ER, PR, HER2 and lymph node status did not impact tumor ADC value.
However, tumors with LVI showed significantly lower ADC values when compared to
tumors without LVI, regardless of the enhancement type, histological grade,
histological type, and LN status. CONCLUSION: Our study shows that ADC could be a
potential clinical adjunct in the evaluation of prognostic factors related to
malignant lesion aggressiveness such as LVI.
PMID- 27501903
TI - Prediction for rupture risk of carotid artery plaques: A comparative study of 3D
GSM and CAS system.
AB - PURPOSE: The study aimed to explore whether GSM based on 3D-ultrasound could
predict rupture of carotid plaques and to quantitatively evaluate the
vulnerability of carotid plaques. MATERIALS AND METHODS: 22 Patients with carotid
plaques enrolled received 3D-US and 3.0T MRI examinations with intervals less
than 48h. Images from two modalities were compared plane by plane. Based on the
MRI analysis of plaques tissue compositions, images were divided into 4 groups:
fibrous group, lipid core group, calcification group and hybrid group. GSM
differences among groups were analyzed and 95% CI was calculated. Based on
CAS(carotid atherosclerosis score)system, MRI images were divided into low risk
group, medium-low risk group, medium-high risk group and high risk group. GSM
differences were compared among groups and 95% CI was calculated. The correlation
between GSM and LRNC% (lipid-rich necrotic core%) was analyzed in medium-high
risk group and high risk group. Coefficient of variation(CoV) was used to compare
the reproducibility of GSM in calcification group and lipid core group. RESULTS:
A total of 164 images were matched between 3D-US and MRI. In the classification
of plaque tissue composition, GSM was the highest in calcification group (n=29,
95%CI: 57.28-70.38) with a significant difference from other groups, whereas the
lowest in lipid core group (n=78, 95% CI:41.79-49.36), but with no significance
compared with the fibrous group and hybrid group. In CAS system, GSM was the
lowest in high risk group (n=19, 95% CI: 26.44-36.56) and there were significant
differences among each group (p<0.05). In high risk group and medium-high risk
group, GSM was negatively correlated with lipid core ratio (r=-0.46, p=0.003).
CoV of GSM in the calcification group(10.87%) was better than in lipid core
group(13.02%), both of them were acceptable. CONCLUSION: GSM obtained by 3D-US
VPQ could evaluate the plaque vulnerability and be served as a new promising
method to predict plaque rupture.
PMID- 27501904
TI - Performance of adaptive iterative dose reduction 3D integrated with automatic
tube current modulation in radiation dose and image noise reduction compared with
filtered-back projection for 80-kVp abdominal CT: Anthropomorphic phantom and
patient study.
AB - OBJECTIVES: Evaluate the performance of Adaptive Iterative Dose Reduction 3D
(AIDR 3D) and compare with filtered-back projection (FBP) regarding radiation
dosage and image quality for an 80-kVp abdominal CT. MATERIALS AND METHODS: An
abdominal phantom underwent four CT acquisitions and reconstruction algorithms
(FBP; AIDR 3D mild, standard and strong). Sixty-three patients underwent
unenhanced liver CT with FBP and standard level AIDR 3D. Further post-acquisition
reconstruction with strong level AIDR 3D was made. Patients were divided into two
groups (< and ?29cm) based on the abdominal effective diameter (Deff) at T12
level. Quantitative (attenuation, noise, and signal-to-noise ratio) and
qualitative (image quality, noise, sharpness, and artifact) analysis by two
readers were assessed and the interobserver agreement was calculated. RESULTS:
Strong level AIDR 3D reduced radiation dose by 72% in the phantom and 47.1% in
the patient study compared with FBP. There was no difference in mean
attenuations. Image noise was the lowest and signal-to-noise ratio the highest
using strong level AIDR 3D in both patient groups. For Deff<29cm, image sharpness
of FBP was significantly different from those of AIDR 3D (P<0.05). For Deff
?29cm, image quality of AIDR 3D was significantly more favorable than FBP
(P<0.05). Interobserver agreement was substantial. CONCLUSIONS: Integrated AIDR
3D allows for an automatic reduction in radiation dose and maintenance of image
quality compared with FBP. Using AIDR 3D reconstruction, patients with larger
abdomen circumference could be imaged at 80kVp.
PMID- 27501905
TI - Modified MR defecography without rectal filling in obstructed defecation
syndrome: Initial experience.
AB - OBJECTIVE: To evaluate the role of dynamic MR defecography before rectal filling
in detecting occult anterior compartment prolapse in patients with obstructed
defecation. METHODS: This prospective study was approved by the ethics committee.
Seventy six females with obstructed defecation underwent dynamic MR defecography
before and after rectal filling. Pre-rectal and post-rectal filling sequences
were interpreted separately by two radiologists on two different settings with a
time interval of one week. Statistical analysis was performed using Wilcoxon's
matched-pairs signed rank test and t-test for matched pairs; differences were
considered statistically significant at p<0.05. RESULTS: Fifty eight females of
76 showed additional anterior compartment derangement, with 27 diagnosed only in
pre-rectal filling sequence (27/58=46.55%). Following rectal filling detected
cystocele in 27 patients was not identified in 14 cases and downgraded in 13.
Similarly, detected uterine prolapse in 17 patients was not visualized in 14
patients and downgraded in 3. Furthermore, rectocele was identified in 7 cases
before gel enema, additional 32 detected after rectal filling. Significant
statistical difference in the detection of both cystocele (p=0.0001) and uterine
prolapse (p=0.0013) was identified in the non-filled sequence. CONCLUSION: Pelvic
floor imaging before rectal filling is significantly better for detection of
anterior compartment prolapse.
PMID- 27501906
TI - Tobacco as platform for a commercial production of cyanophycin.
AB - Cyanophycin (CP) is a proteinogenic polymer that can be substituted for petroleum
in the production of plastic compounds and can also serve as a source of valuable
dietary supplements. However, because there is no economically feasible system
for large-scale industrial production, its application is limited. In order to
develop a low-input system, CP-synthesis was established in the two commercial
Nicotiana tabacum (N. tabacum) cultivars 'Badischer Geudertheimer' (BG) and
'Virginia Golta' (VG), by introducing the cyanophycin-synthetase gene from
Thermosynecchococcus elongatus BP-1 (CphATe) either via crossbreeding with
transgenic N. tabacum cv. Petit Havana SR1 (PH) T2 individual 51-3-2 or by
agrobacterium-mediated transformation. Both in F1 hybrids (max. 9.4% CP/DW) and
T0 transformants (max. 8.8% CP/DW), a substantial increase in CP content was
achieved in leaf tissue, compared to a maximum of 1.7% CP/DW in PH T0
transformants of Huhns et al. (2008). In BG CP, yields were homogenous and there
was no substantial difference in the variation of the CP content between primary
transformants (T0), clones of T0 individuals, T1 siblings and F1 siblings of
hybrids. Therefore, BG meets the requirements for establishing a master seed bank
for continuous and reliable CP-production. In addition, it was shown that the
polymer is not only stable in planta but also during silage, which simplifies
storage of the harvest prior to isolation of CP.
PMID- 27501907
TI - A two-stage cognitive theory of the positive symptoms of psychosis. Highlighting
the role of lowered decision thresholds.
AB - OBJECTIVES: We outline a two-stage heuristic account for the pathogenesis of the
positive symptoms of psychosis. METHODS: A narrative review on the empirical
evidence of the liberal acceptance (LA) account of positive symptoms is
presented. HYPOTHESIS: At the heart of our theory is the idea that psychosis is
characterized by a lowered decision threshold, which results in the premature
acceptance of hypotheses that a nonpsychotic individual would reject. Once the
hypothesis is judged as valid, counterevidence is not sought anymore due to a
bias against disconfirmatory evidence as well as confirmation biases,
consolidating the false hypothesis. As a result of LA, confidence in errors is
enhanced relative to controls. Subjective probabilities are initially low for
hypotheses in individuals with delusions, and delusional ideas at stage 1 (belief
formation) are often fragile. In the course of the second stage (belief
maintenance), fleeting delusional ideas evolve into fixed false beliefs,
particularly if the delusional idea is congruent with the emotional state and
provides "meaning". LA may also contribute to hallucinations through a
misattribution of (partially) normal sensory phenomena. Interventions such as
metacognitive training that aim to "plant the seeds of doubt" decrease positive
symptoms by encouraging individuals to seek more information and to attenuate
confidence. The effect of antipsychotic medication is explained by its doubt
inducing properties. LIMITATIONS: The model needs to be confirmed by longitudinal
designs that allow an examination of causal relationships. Evidence is currently
weak for hallucinations. CONCLUSIONS: The theory may account for positive
symptoms in a subgroup of patients. Future directions are outlined.
PMID- 27501908
TI - Phytosterol structured algae oil nanoemulsions and powders: improving antioxidant
and flavor properties.
AB - Algae oil, enriched with omega-3 long-chain polyunsaturated fatty acids (omega-3
LC-PUFA), is known for its health benefits. However, protection against lipid
oxidation as well as masking of unpleasant fishy malodors in algae oil enriched
foods is a big challenge to achieve. In this study, we firstly achieved a one-pot
ultrasound emulsification strategy (alternative heating-homogenization) to
prepare phytosterol structured thermosensitive algae oil-in-water nanoemulsion
stabilized by quillaja saponin. After spray drying, the resulting algae oil
powders from the structured nanoemulsion templates exhibit an excellent
reconstructed behavior, even after 30 d of storage. Furthermore, an enhanced
oxidative stability was obtained by reducing both the primary and secondary
oxidation products through formulation with beta-sitosterol and gamma-oryzanol,
which are natural antioxidants. Following the results of headspace volatiles
using dynamic headspace-gas chromatography-mass spectrometry (DHS-GC-MS), it was
clear that the structured algae oil-loaded nanoemulsion and powder had lower
levels of fishy off-flavour (e.g., (Z)-heptenal, decanal, ethanone, and
hexadecenoic acid), whereas the control emulsion and oil powder without structure
performed worse. This study demonstrated that the structure from phytosterols is
an effective strategy to minimize the fishy off-flavour and maximize oxidative
stability of both algae oil nanoemulsions and spray-dried powders, and opens up
the possibility of formulation design in polyunsaturated oil encapsulates as
novel delivery systems to apply in functional foods and beverages.
PMID- 27501909
TI - Oleanolic acid-NO donor-platinum(II) trihybrid molecules: Targeting cytotoxicity
on hepatoma cells with combined action mode and good safety.
AB - By taking advantage of good affinity of oleanolic acid (OA) to the bile acid
transporter, a series of hybrid compounds from oleanolic acid (OA) or OA-nitric
oxide (NO) donor derivative coordinating to platinum(II) complexes were designed
and synthesized. As expected, complexes 1c and 1d showed selective cytotoxicity
to hepatoma carcinoma cells (e.g. HepG2, SMMC-7721, BEL-7402 cells) rather than
other tumor cells. Interestingly, they had only a weak toxicity to normal hepatic
cells (e.g. LO2 cells). Mechanism studies revealed that 1c could effectively bind
to the ligand domain of the farnesoid X receptor and maintain the normal function
of liver cells. Furthermore, the NO donor moiety could moderately release
cytotoxic NO and finally enhance the cytotoxic effect, while the cytotoxicity of
the corresponding complexes was decreased when the cells were pretreated with NO
scavenger. Additionally, the agarose gel electrophoresis revealed that the Pt(II)
part could also offer DNA binding activity, suggesting the complexes possess a
combined action mode which may help to overcome the resistance of cisplatin. The
flow cytometry studies found that 1c caused tumor apoptosis and blocked cell
cycle progression in the G2 phase.
PMID- 27501910
TI - Assessing the physiological relevance of alternate architectures of the p7
protein of hepatitis C virus in different environments.
AB - The viroporin p7 of the hepatitis C virus forms multimeric channels eligible for
ion transport across the endoplasmic reticulum membrane. Currently the subject of
many studies and discussion, the molecular assembly of the ion channel and the
structural characteristics of the p7 monomer are not yet fully understood.
Structural investigation of p7 has been carried out only in detergent
environments, making the interpretation of the experimental results somewhat
questionable. Here, we analyze by means of molecular dynamics simulations the
structure of the p7 monomer as a function of its sequence, initial conformation
and environment. We investigate the conductance properties of three models of a
hexameric p7 ion channel by examining ion translocation in a pure lipid bilayer.
It is noteworthy that although none of the models reflects the experimentally
observed trend to conduct preferentially cations, we were able to identify the
position and orientation of titratable acidic or basic residues playing a crucial
role in ion selectivity and in the overall conductance of the channel. In
addition, too compact a packing of the monomers leads to channel collapse rather
than formation of a reasonable pore, amenable to ion translocation. The present
findings are envisioned to help assess the physiological relevance of p7 ion
channel models consisting of multimeric structures obtained in non-native
environments.
PMID- 27501911
TI - Arylazolyl(azinyl)thioacetanilides. Part 20: Discovery of novel
purinylthioacetanilides derivatives as potent HIV-1 NNRTIs via a structure-based
bioisosterism approach.
AB - By means of structure-based bioisosterism approach, a series of novel
purinylthioacetanilide derivatives were designed, synthesized and evaluated as
potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Some of
the tested compounds were found to be active against wild-type (WT) HIV-1(IIIB)
with EC50 in the range of 0.78-4.46MUM. Among them, LAD-8 displayed the most
potent anti-HIV activity (EC50=0.78MUM, SI=24). In addition, LBD-6 showed
moderate activity against L100I mutant (EC50=5.64MUM) and double mutant strain
RES056 (EC50=22.24MUM). Preliminary structure-activity relationships (SARs) were
discussed in detail. Molecular modeling study was used to predict the optimal
conformation in the NNRTI binding site, which may play a guiding role in further
rational optimization.
PMID- 27501912
TI - Origins of regioselectivity in 1,3-dipolar cycloadditions of nitrile oxides with
alkynylboronates.
AB - Density functional theory (M06-2X) studies of the regioselectivity of 1,3-dipolar
cycloaddition reactions of benzo and mesitonitrile oxides with alkynyl pinacol
and MIDA boronates are reported. Calculated relative free energies of activation
reproduce the experimentally observed product ratios. The electronic energies of
activation are found to be mainly controlled by distortion energies required to
achieve the transition states. Both electronic and steric effects influence
regioselectivities.
PMID- 27501913
TI - Occupying a flat subpocket in a tRNA-modifying enzyme with ordered or disordered
side chains: Favorable or unfavorable for binding?
AB - Small-molecule ligands binding with partial disorder or enhanced residual
mobility are usually assumed as unfavorable with respect to their binding
properties. Considering thermodynamics, disorder or residual mobility is
entropically favorable and contributes to the Gibbs energy of binding. In the
present study, we analyzed a series of congeneric ligands inhibiting the tRNA
modifying enzyme TGT. Attached to the parent lin-benzoguanine scaffold,
substituents in position 2 accommodate in a flat solvent-exposed pocket and
exhibit varying degree of residual mobility. This is indicated in the crystal
structures by enhanced B-factors, reduced occupancies, or distributions over
split conformers. MD simulations of the complexes suggest an even larger scatter
over several conformational families. Introduction of a terminal acidic group
fixes the substituent by a salt-bridge to an Arg residue. Overall, all
substituted derivatives show the same affinity underpinning that neither order
nor disorder is a determinant factor for binding affinity. The additional salt
bridge remains strongly solvent-exposed and thus does not contribute to affinity.
MD suggests temporary fluctuation of this contact.
PMID- 27501914
TI - Depression risk in patients with late-onset rheumatoid arthritis in Germany.
AB - GOAL: The goal of this study was to determine the prevalence of depression and
its risk factors in patients with late-onset rheumatoid arthritis (RA) treated in
German primary care practices. METHODS: Longitudinal data from general practices
(n=1072) throughout Germany were analyzed. Individuals initially diagnosed with
RA (2009-2013) were identified, and 7301 patients were included and matched (1:1)
to 7301 controls. The primary outcome measure was the initial diagnosis of
depression within 5 years after the index date in patients with and without RA.
Cox proportional hazards models were used to adjust for confounders. RESULTS: The
mean age was 72.2 years (SD: 7.6 years). A total of 34.9 % of patients were men.
Depression diagnoses were present in 22.0 % of the RA group and 14.3 % of the
control group after a 5-year follow-up period (p < 0.001). In the multivariate
regression model, RA was a strong risk factor for the development of depression
(HR: 1.55, p < 0.001). There was significant interaction of RA and diagnosed
inflammatory polyarthropathies (IP) (RA*IP interaction: p < 0.001). Furthermore,
dementia, cancer, osteoporosis, hypertension, and diabetes were associated with a
higher risk of developing depression (p values <0.001). CONCLUSION: The risk of
depression is significantly higher in patients with late-onset RA than in
patients without RA for subjects treated in primary care practices in Germany. RA
patients should be screened routinely for depression in order to ensure improved
treatment and management.
PMID- 27501917
TI - The influence of the electronic specific heat on swift heavy ion irradiation
simulations of silicon.
AB - The swift heavy ion (SHI) irradiation of materials is often modelled using the
two-temperature model. While the model has been successful in describing SHI
damage in metals, it fails to account for the presence of a bandgap in
semiconductors and insulators. Here we explore the potential to overcome this
limitation by explicitly incorporating the influence of the bandgap in the
parameterisation of the electronic specific heat for Si. The specific heat as a
function of electronic temperature is calculated using finite temperature density
functional theory with three different exchange correlation functionals, each
with a characteristic bandgap. These electronic temperature dependent specific
heats are employed with two-temperature molecular dynamics to model ion track
creation in Si. The results obtained using a specific heat derived from density
functional theory showed dramatically reduced defect creation compared to models
that used the free electron gas specific heat. As a consequence, the track radii
are smaller and in much better agreement with experimental observations. We also
observe a correlation between the width of the band gap and the track radius,
arising due to the variation in the temperature dependence of the electronic
specific heat.
PMID- 27501915
TI - The Role of Molecular Diagnostics in the Management of Patients with Gliomas.
AB - OPINION STATEMENT: The revised World Health Organization (WHO) classification of
tumors of the central nervous system of 2016 combines biology-driven molecular
marker diagnostics with classical histological cancer diagnosis. Reclassification
of gliomas by molecular similarity beyond histological boundaries improves
outcome prediction and will increasingly guide treatment decisions. This change
in paradigms implies more personalized and eventually more efficient therapeutic
approaches, but the era of molecular targeted therapies for gliomas is yet at its
onset. Promising results of molecularly targeted therapies in genetically less
complex gliomas with circumscribed growth such as subependymal giant cell
astrocytoma or pilocytic astrocytoma support further development of molecularly
targeted therapies. In diffuse gliomas, several molecular markers that predict
benefit from alkylating agent chemotherapy have been identified in recent years.
For example, co-deletion of chromosome arms 1p and 19q predicts benefit from
polychemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) in
patients with anaplastic oligodendroglioma, and the presence of 1p/19q co
deletion was integrated as a defining feature of oligodendroglial tumors in the
revised WHO classification. However, the tremendous increase in knowledge of
molecular drivers of diffuse gliomas on genomic, epigenetic, and gene expression
levels has not yet translated into effective molecular targeted therapies.
Multiple reasons account for the failure of early clinical trials of molecularly
targeted therapies in diffuse gliomas, including the lack of molecular entry
controls as well as pharmacokinetic and pharmacodynamics issues, but the key
challenge of specifically targeting the molecular backbone of diffuse gliomas is
probably extensive clonal heterogeneity. A more profound understanding of clonal
selection, alternative activation of oncogenic signaling pathways, and genomic
instability is warranted to identify effective combination treatments and
ultimately improve survival.
PMID- 27501916
TI - Helminth-Tuberculosis Co-infection: An Immunologic Perspective.
AB - Over 2 billion people worldwide are infected with helminths (worms). Similarly,
infection with Mycobacterium tuberculosis (Mtb) occurs in over a third of the
world's population, often with a great degree of geographical overlap with
helminth infection. Interestingly, the responses induced by the extracellular
helminths and those induced by the intracellular Mtb are often mutually
antagonistic and, as a consequence, can result in impaired (or cross-regulated)
host responses to either of the infecting pathogens. In this review, we outline
the nature of the immune responses induced by infections with helminths and
tuberculosis (TB) and then provide data from both experimental models and human
studies that illustrate how the immune response engendered by helminth parasites
modulates Mtb-specific responses in helminth-TB coinfection.
PMID- 27501918
TI - Characterisation of a novel, high affinity and selective alphavbeta6 integrin RGD
mimetic radioligand.
AB - The alpha-v beta-6 (alphavbeta6) integrin has been identified as playing a key
role in the activation of transforming growth factor-beta (TGFbeta) that is
hypothesised to be pivotal in the development of cancer and fibrotic diseases.
Therefore, the alphavbeta6 integrin is an attractive therapeutic target for these
debilitating diseases and a drug discovery programme to identify small molecule
alphavbeta6 selective arginyl-glycinyl-aspartic acid (RGD)-mimetics was initiated
within GlaxoSmithKline. The primary aim of this study was to pharmacologically
characterise the binding to alphavbeta6 of a novel clinical candidate, compound
1, using a radiolabelled form. Radioligand binding studies were completed with
[(3)H]compound 1 against the human and mouse soluble protein forms of alphavbeta6
to determine accurate affinity estimates and binding kinetics. The selectivity of
compound 1 for the RGD integrin family was also determined using saturation
binding studies (alphavbeta1, alphavbeta3, alphavbeta5, alphavbeta8, alpha5beta1
and alpha8beta1 integrins) and fibrinogen-induced platelet aggregation
(alphaIIbbeta3 integrin). In addition, the relationship between divalent metal
cation type and concentration and alphavbeta6 RGD site binding was also
investigated. Compound 1 has been demonstrated to bind with extremely high
affinity and selectivity for the alphavbeta6 integrin and has the potential as a
clinical tool and therapeutic for investigating the role of alphavbeta6 in a
range of disease states both pre-clinically and clinically. In addition, this is
the first study that has successfully applied radioligand binding to the RGD
integrin field to accurately determine the affinity and selectivity profile of a
small molecule RGD-mimetic.
PMID- 27501919
TI - Dehydroepiandrosterone-induced changes in mitochondrial proteins contribute to
phenotypic alterations in hepatoma cells.
AB - Dehydroepiandrosterone (DHEA)-induced growth arrest of hepatoma cells is
associated with metabolic disturbance. Our previous study has suggested that DHEA
may cause cellular energy drain. It is possible that mitochondrial dysfunction
may be mechanistically implicated in DHEA-induced changes in cellular phenotype.
Treatment of SK-Hep-1 cells with DHEA caused significant reduction in
proliferation, colony formation, and growth in semi-solid medium. Such changes in
cellular phenotype were associated with mitochondrial depolarization, increase in
mitochondrial mass, and decrease in respiratory activity. Level of reactive
oxygen species (ROS) increased in DHEA-treated cells. To explore the mechanistic
aspect of DHEA-induced mitochondrial dysfunction, we employed SILAC approach to
study the changes in the mitoproteome of SK-Hep-1 cells after DHEA treatment.
Respiratory chain complex proteins such as NDUFB8 and SDHB were differentially
expressed. Of mitochondrial proteins with altered expression, FAST kinase domain
containing protein 2 (FASTKD2) showed significantly reduced expression. Exogenous
expression of FASTKD2 in SK-Hep-1 cells increased their resistance to growth
inhibitory effect of DHEA, though it alone did not affect cell growth. FASTKD2
expression partially reversed the effect of DHEA on mitochondria, and reduced
DHEA-induced ROS generation. Our results suggest that DHEA induces changes in
mitochondrial proteins and respiratory activity, and contributes to growth
arrest. FASTKD2 may be an important regulator of mitochondrial physiology, and
represent a downstream target for DHEA.
PMID- 27501920
TI - Kinetic binding and activation profiles of endogenous tachykinins targeting the
NK1 receptor.
AB - Ligand-receptor binding kinetics (i.e. association and dissociation rates) are
emerging as important parameters for drug efficacy in vivo. Awareness of the
kinetic behavior of endogenous ligands is pivotal, as drugs often have to compete
with those. The binding kinetics of neurokinin 1 (NK1) receptor antagonists have
been widely investigated while binding kinetics of endogenous tachykinins have
hardly been reported, if at all. Therefore, the aim of this research was to
investigate the binding kinetics of endogenous tachykinins and derivatives
thereof and their role in the activation of the NK1 receptor. We determined the
binding kinetics of seven tachykinins targeting the NK1 receptor. Dissociation
rate constants (koff) ranged from 0.026+/-0.0029min-1 (Sar9,Met(O2)11-SP) to
0.21+/-0.015min-1 (septide). Association rate constants (kon) were more diverse:
substance P (SP) associated the fastest with a kon value of 0.24+/-0.046nM-1min-1
while neurokinin A (NKA) had the slowest association rate constant of 0.001+/
0.0002nM-1min-1. Kinetic binding parameters were highly correlated with potency
and maximal response values determined in label-free impedance-based experiments
on U-251 MG cells. Our research demonstrates large variations in binding kinetics
of tachykinins which correlate to receptor activation. These findings provide new
insights into the ligand-receptor interactions of tachykinins and underline the
importance of measuring binding kinetics of both drug candidates and competing
endogenous ligands.
PMID- 27501921
TI - Hybrid agent-based model for quantitative in-silico cell-free protein synthesis.
AB - An advanced vision of the mRNA translation is presented through a hybrid modeling
approach. The dynamics of the polysome formation was investigated by computer
simulation that combined agent-based model and fine-grained Markov chain
representation of the chemical kinetics. This approach allowed for the
investigation of the polysome dynamics under non-steady-state and non-continuum
conditions. The model is validated by the quantitative comparison of the
simulation results and Luciferase protein production in cell-free system, as well
as by testing of the hypothesis regarding the two possible mechanisms of the
Edeine antibiotic. Calculation of the Hurst exponent demonstrated a relationship
between the microscopic properties of amino acid elongation and the fractal
dimension of the translation duration time series. The temporal properties of the
amino acid elongation have indicated an anti-persistent behavior under low mRNA
occupancy and evinced the appearance of long range interactions within the mRNA
ribosome system for high ribosome density. The dynamic and temporal
characteristics of the polysomal system presented here can have a direct impact
on the studies of the co-translation protein folding and provide a validated
platform for cell-free system studies.
PMID- 27501922
TI - New Evidence That Nonlinear Source-Filter Coupling Affects Harmonic Intensity and
fo Stability During Instances of Harmonics Crossing Formants.
AB - The traditional source-filter theory of voice production describes a linear
relationship between the source (glottal flow pulse) and the filter (vocal
tract). Such a linear relationship does not allow for nor explain how changes in
the filter may impact the stability and regularity of the source. The objective
of this experiment was to examine what effect unpredictable changes to vocal
tract dimensions could have on fo stability and individual harmonic intensities
in situations in which low frequency harmonics cross formants in a fundamental
frequency glide. To determine these effects, eight human subjects (five male,
three female) were recorded producing fo glides while their vocal tracts were
artificially lengthened by a section of vinyl tubing inserted into the mouth. It
was hypothesized that if the source and filter operated as a purely linear
system, harmonic intensities would increase and decrease at nearly the same rates
as they passed through a formant bandwidth, resulting in a relatively symmetric
peak on an intensity-time contour. Additionally, fo stability should not be
predictably perturbed by formant/harmonic crossings in a linear system. Acoustic
analysis of these recordings, however, revealed that harmonic intensity peaks
were asymmetric in 76% of cases, and that 85% of fo instabilities aligned with a
crossing of one of the first four harmonics with the first three formants. These
results provide further evidence that nonlinear dynamics in the source-filter
relationship can impact fo stability as well as harmonic intensities as harmonics
cross through formant bandwidths.
PMID- 27501923
TI - Voice in Friedreich Ataxia.
AB - BACKGROUND: Friedreich Ataxia (FRDA) is the most common hereditary ataxia, with
dysarthria as one of its key clinical signs. OBJECTIVE: To describe the voice
profile of individuals with FRDA to inform outcome marker development and goals
of speech therapy. METHODS: Thirty-six individuals with FRDA and 30 age-matched
controls provided sustained vowel and connected speech samples. Speech and voice
samples were analyzed acoustically using the Analysis of Dysphonia in Speech and
Voice program and perceptually using the Consensus Auditory-Perceptual Evaluation
of Voice form. Correlations between dysphonia and overall dysarthria severity,
demographic, clinical, and genetic information were explored. RESULTS:
Individuals with FRDA presented with mild dysphonia characterized by hoarseness
(combined roughness and breathiness), increased strain, and altered pitch
variability (increased in vowel productions; slightly decreased on reading
samples). Acoustically, individuals with FRDA had significantly higher scores on
the Cepstral Spectral Index of Dysphonia during vowel production. A combination
of perceptual and acoustic measures of dysphonia used in this study was quite
effective in categorizing the FRDA versus control participants, with >80% overall
accuracy. CONCLUSIONS: Although dysphonia severity in FRDA did not correlate
significantly with overall disease severity, speaking rate and syllabic duration
significantly correlated with age at disease onset and disease duration, and also
have an effect on listener perception of dysphonia. The relationship between
dysphonia and dysarthria in FRDA suggests that reducing overall dysphonia
severity via therapeutic techniques that improve phonatory stability and increase
speaking rate is a viable target for speech therapy.
PMID- 27501924
TI - Expression, purification and characterization of GAPDH-ChSase ABC I from Proteus
vulgaris in Escherichia coli.
AB - Chondroitinases (ChSases) are a family of polysaccharide lyases that can
depolymerize high molecular weight chondroitin sulfate (CS) and dermatan sulfate
(DS). In this study, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is
stably expressed in different cells like normal cells and cancer cells and the
expression is relatively insensitive to experimental conditions, was expressed as
a fusion protein with ChSase ABC I. Results showed that the expression level and
enzyme activity of GAPDH-ChSase ABC I were about 2.2 and 3.0 times higher than
those of ChSase ABC I. By optimization of fermentation conditions, higher
productivity of ChSase ABC I was achieved as 880 +/- 61 IU/g wet cell weight
compared with the reported ones. The optimal temperature and pH of GAPDH-ChSase
ABC I were 40 degrees C and 7.5, respectively. GAPDH-ChSase ABC I had a kcat/Km
of 131 +/- 4.1 L/MUmol s and the catalytic efficiency was decreased as compared
to ChSase ABC I. The relative activity of GAPDH-ChSase ABC I remained 89% after
being incubated at 30 degrees C for 180 min and the thermostability of ChSase
ABC I was enhanced by GAPDH when it was incubated at 30, 35, 40 and 45 degrees
C.
PMID- 27501925
TI - Health Sector Reform: Time to Introspect.
PMID- 27501926
TI - Chlamydia trachomatis infection and HPV/Chlamydia trachomatis co-infection among
HPV-vaccinated young women at the beginning of their sexual activity.
AB - PURPOSE: This study investigated the prevalence of Chlamydia trachomatis
infection, co-infection with Human Papillomavirus (HPV) and associated risk
factors in a cohort of sexually active young women enrolled in an ongoing trial
on HPV vaccination at the European Institute of Oncology (IEO, Milan, Italy).
METHODS: Cervical samples were collected from 591 girls (median age 18.8 years)
at the beginning of their sexual activity. At the time of sample collection, 354
women had not yet been vaccinated, and 237 women had been vaccinated for at least
12 months. All samples were analyzed through a molecular assay for the detection
of C. trachomatis infection. Demographic, behavioral risk factors and high-risk
HPV (HR-HPV) status were investigated. RESULTS: The prevalence of C. trachomatis
infection was 4.9 % and HPV/C. trachomatis co-infection rate was 1.5 %. The exact
analysis has not underlined statistical significance for the variables
considered, except for the infection with HR-HPV (p < 0.001). The prevalence of
C. trachomatis infection among women who had not been immunized and those already
vaccinated was similar (5.6 vs 3.8 %). However, the rate of HPV/C. trachomatis co
infection was twice as high in unvaccinated women (2 %) compared to vaccinated
women (0.8 %). CONCLUSIONS: Over 16 % of young women had at least one of the two
STIs investigated. The risk of C. trachomatis infection was higher in HR-HPV
infected compared to HR-HPV uninfected young women. The rate of co-infection was
halved in HPV-vaccinated compared to unvaccinated women. This study underlines
that HPV vaccination can confer benefits also in terms of co-infections
prevention, leading to a decreased risk of developing cervical malignancies.
PMID- 27501927
TI - Induction of labor: does indication matter?
AB - PURPOSE: Labor induction is performed in 20 % of pregnancies. However, the impact
of the indications for induction on its failure rate has hardly been
investigated. We aimed to evaluate the association of indications for labor
induction with failure rate. METHODS: Background and delivery-related data were
retrospectively collected for all women with a viable term singleton pregnancy,
who underwent labor induction with a PGE2 vaginal insert in 2013-2014. Reasons
for induction were categorized as maternal indications, hypertensive disorders,
premature rupture of membranes, and fetal indications. Induction failure was
defined as Bishop score <=7 at 24 h after PGE2 administration, cesarean delivery
due to latent phase dystocia or removal of the insert due to non-reassuring fetal
heart rate followed by emergency cesarean delivery. Outcome measures were rate of
induction failure (primary) and rate of cesarean delivery (secondary). RESULTS:
The cohort included 1066 women. Those who failed induction (n = 213, 20 %) were
more likely to be nulliparous (69.5 vs. 45.7 %, p < 0.0001), older (31 vs. 30
years, p = 0.047), and at an earlier gestational age (39.4 vs. 40.0 weeks, p <
0.0001). Among nulliparous women, maternal indications were significantly
associated with induction failure (aOR 2.52, 95 % CI 1.28-4.95, p = 0.007) and
cesarean delivery (aOR 2.36, 95 % CI 0.40-2.29, p = 0.019). Among multiparous
women, hypertensive disorders (aOR 7.26, 95 % CI 1.89-27.87, p = 0.004) and
maternal indications (aOR 4.22, 95 %CI 1.14-15.58, p = 0.031) were significantly
associated with induction failure but not cesarean delivery. CONCLUSIONS: The
indication for induction of labor may impact its failure rate.
PMID- 27501928
TI - Impact of combined hormonal contraceptives on vessels functionality.
AB - PURPOSE: To evaluate the dynamic and static retinal vascular functionality in
young females using combined hormonal contraceptive (CHC). METHODS: Thirty-eight
consecutive young female subjects were enrolled in this study between January
2015 and December 2015. Subjects were divided in two groups: CHC group, defined
as CHC use for >=6 months, and control group, defined as no current and prior CHC
use. Participants underwent a dynamic and static retinal vessel analysis using
the Dynamic Vessel Analyzer (DVA, Imedos, Jena, Germany). RESULTS: Seventeen
subjects continuously took CHC for 54.6 +/- 29.3 months, while 21 subjects
belonged to control group. No difference was found between the CHC and control
groups for age (p = 0.1), smoking status (p = 0.6), and systolic (p = 0.3) and
diastolic (p = 0.1) blood pressure. With regard to dynamic analysis, women taking
CHC exhibited a marked significant vasoconstriction following flicker stimulation
in comparison with control group (-2.43 +/- 2.5 vs 0.63 +/- 2.1, respectively; p
= 0.0002). No significant difference was observed between groups for mean
arterial (p = 0.2) and venous dilatations (p = 0.3), arteriovenous ratio (p =
0.09), central retinal artery equivalent (p = 0.4), and central retinal venous
equivalent (p = 0.5). CONCLUSIONS: CHC may affect vessel reactivity to flicker
light by increasing arteries constriction. This may reflect systemic changes in
vascular functionality in subjects using CHC. Moreover, CHC should be considered
as a confounding bias in studies involving DVA.
PMID- 27501929
TI - Premature rupture of the membranes at term: time to reevaluate the management.
AB - PURPOSE: To compare maternal and neonatal outcomes in induced vs. expectant
management of term PROM. METHODS: This retrospective study included patients with
term PROM. A total of 325 were enrolled: 213 managed expectantly and 112 induced
at admission and matched according to gestational age. Expectant management group
patients were allowed to defer labour induction up to 48 h. Primary outcome
measures were maternal or foetal signs of infection (chorioamnionitis, early
neonatal sepsis or postpartum endometritis) and prolonged maternal
hospitalization. Secondary outcome was caesarean delivery rate. RESULTS: All
group characteristics were comparable except that expectant management included
more nulliparous women. Women managed expectantly had a higher rate of prolonged
hospitalization [15 (7 %) vs. 2 (1.8 %); P = 0.043] as an indication of maternal
complications, compared to induction management. They also had a higher rate of
caesarean delivery [34 (16.4 %) vs. 8 (7.1 %), respectively; P = 0.024].
Adjustment for parity did not change the results. Early neonatal outcomes were
similar between groups. CONCLUSIONS: Expectant management increases the
likelihood of caesarean delivery and prolonged maternal hospitalization. This
should be considered when advising patients with term PROM regarding labour
induction.
PMID- 27501930
TI - The Impact of Electronic Health Records on Risk Management of Information Systems
in Australian Residential Aged Care Homes.
AB - To obtain indications of the influence of electronic health records (EHR) in
managing risks and meeting information system accreditation standard in
Australian residential aged care (RAC) homes. The hypothesis to be tested is that
the RAC homes using EHR have better performance in meeting information system
standards in aged care accreditation than their counterparts only using paper
records for information management. Content analysis of aged care accreditation
reports from the Aged Care Standards and Accreditation Agency produced between
April 2011 and December 2013. Items identified included types of information
systems, compliance with accreditation standards, and indicators of failure to
meet an expected outcome for information systems. The Chi-square test was used to
identify difference between the RAC homes that used EHR systems and those that
used paper records in not meeting aged care accreditation standards. 1,031
(37.4%) of 2,754 RAC homes had adopted EHR systems. Although the proportion of
homes that met all accreditation standards was significantly higher for those
with EHR than for homes with paper records, only 13 RAC homes did not meet one or
more expected outcomes. 12 used paper records and nine of these failed the
expected outcome for information systems. The overall contribution of EHR to
meeting aged care accreditation standard in Australia was very small. Risk
indicators for not meeting information system standard were no access to accurate
and appropriate information, failure in monitoring mechanisms, not reporting
clinical incidents, insufficient recording of residents' clinical changes, not
providing accurate care plans, and communication processes failure. The study has
provided indications that use of EHR provides small, yet significant advantages
for RAC homes in Australia in managing risks for information management and in
meeting accreditation requirements. The implication of the study for introducing
technology innovation in RAC in Australia is discussed.
PMID- 27501931
TI - Diversity of helminth parasites in aquatic invertebrate hosts in Latin America:
how much do we know?
AB - Helminths in aquatic invertebrate hosts have been overlooked in comparison with
vertebrate hosts. Therefore, the known diversity, ecology and distribution of
these host-parasite systems are very limited in terms of their taxonomic
diversity, habitat and geographic regions. In this study we examined the
published literature on helminth parasites of aquatic invertebrates from Latin
America and the Caribbean (LAC) to identify the state of the knowledge in the
region and to identify patterns of helminth diversity. Results showed that 67% of
the literature is from Argentina, Mexico and Brazil. We found records for 772
host-parasite associations. Most records relate to medically or economically
important hosts. Molluscs were the most studied host group with 377 helminth
records (80% trematodes). The lymnaeids and planorbids were the most studied
molluscs across LAC. Arthropods were the second most studied host group with 78
helminth records (trematodes 38%, cestodes 24% and nematodes 20%), with shrimps
and crabs being the most studied hosts. Host species with the largest number of
helminth taxa were those with a larger sampling effort through time, usually in a
small country region. No large geographical-scale studies were identified. In
general, the knowledge is still too scarce to allow any zoogeographical or
helminth diversity generalization, as most hosts have been studied locally and
the studies on invertebrate hosts in LAC are substantially uneven among
countries.
PMID- 27501932
TI - Dynamically Arranging Gold Nanoparticles on DNA Origami for Molecular Logic
Gates.
AB - In molecular engineering, DNA molecules have been extensively studied owing to
their capacity for accurate structural control and complex programmability.
Recent studies have shown that the versatility and predictability of DNA origami
make it an excellent platform for constructing nanodevices. In this study, we
developed a strand-displacing strategy to selectively and dynamically release
specific gold nanoparticles (AuNPs) on a rectangular DNA origami. A set of DNA
logic gates ("OR", "AND", and "three-input majority gate") were established based
on this strategy, in which computing results were identified by disassembly
between the AuNPs and DNA origami. The computing results were detected using
experimental approaches such as gel electrophoresis and transmission electron
microscopy (TEM). This method can be used to assemble more complex nanosystems
and may have potential applications for molecular engineering.
PMID- 27501934
TI - Authors' Response: Health Benefits/Hazards Associated with Companion Animal
Exposure Might be Endpoint-and-Animal Specific.
PMID- 27501935
TI - Cetrimide-induced oral mucositis: an unusual adverse drug reaction.
PMID- 27501933
TI - Meta-Analysis of BDNF Levels in Autism.
AB - Brain-derived neurotrophic factor (BDNF) centrally mediates growth,
differentiation and survival of neurons, and the synaptic plasticity that
underlies learning and memory. Recent meta-analyses have reported significantly
lower peripheral BDNF among individuals with schizophrenia, bipolar disorder, and
depression, compared with controls. To evaluate the role of BDNF in autism, and
to compare autism to psychotic-affective disorders with regard to BDNF, we
conducted a meta-analysis of BDNF levels in autism. Inclusion criteria were met
by 15 studies, which included 1242 participants. The meta-analysis estimated a
significant summary effect size of 0.33 (95 % CI 0.21-0.45, P < 0.001),
suggesting higher BDNF in autism than in controls. The studies showed notable
heterogeneity, but no evidence of publication biases. Higher peripheral BDNF in
autism is concordant with several neurological and psychological theories on the
causes and symptoms of this condition, and it contrasts notably with the lower
levels of BDNF found in schizophrenia, bipolar disorder, and depression.
PMID- 27501937
TI - Increasing severity of traumatic brain injury is associated with an increased
risk of subsequent headache or migraine: a retrospective cohort study of U.S.
active duty service members, 2006-2015.
AB - Traumatic brain injury (TBI) is a common injury in the U.S. Compared to the
general population, military service members can be at increased risk for TBI
because of the nature of their work. Sequelae of TBI, such as headache or
migraine, can lead to military duty limitations or separation from service. To
determine whether the severity of TBI is associated with the risk of these
sequelae, this 2006-2015 retrospective cohort study compared the incidence of
diagnosed headache or migraine among all service members with a first-time mild
or moderate/severe TBI (N=111,018) against a matched sample without any history
of TBI. Risk increased according to the severity of TBI. Compared to service
members without TBI, those who sustained a mild TBI were 3.99 times more likely
to have a headache or migraine, and those with a moderate/severe TBI were 8.89
times more likely. Patients, medical providers, and military leaders can use
these results to guide care after a TBI. Early identification of those at higher
risk of these sequelae could improve medical management and reduce disability.
PMID- 27501936
TI - A HER2 selective theranostic agent for surgical resection guidance and
photodynamic therapy.
AB - In many cancers early intervention involves surgical resection of small localised
tumour masses. Inadequate resection leads to recurrence whereas overzealous
treatment can lead to organ damage. This work describes production of a HER2
targeting antibody Fab fragment dual conjugated to achieve both real time near
infrared fluorescent imaging and photodynamic therapy. The use of fluorescence
emission from a NIR-dye could be used to guide resection of tumour bulk, for
example during endoscopic diagnosis for oesophago-gastric adenocarcinoma, this
would then be followed by activation of the photodynamic therapeutic agent to
destroy untreated localised areas of cancer infiltration and tumour infiltrated
lymph nodes. This theranostic agent was prepared from the Fab fragment of
trastuzumab initially by functional disulfide re-bridging and site-specific click
reaction of a NIR-dye. This was followed by further reaction with a novel pre
activated form of the photosensitiser chlorin e6 with the exposed fragments'
lysine residues. Specific binding of the theranostic agent was observed in vitro
with a HER2 positive cell line and cellular near-infrared fluorescence was
observed with flow cytometry. Specific photo-activity of the conjugates when
exposed to laser light was observed with HER2 positive but not HER2 negative cell
lines in vitro, this selectivity was not seen with the unconjugated drug. This
theranostic agent demonstrates that two different photo-active functions can be
coupled to the same antibody fragment with little interference to their
independent activities.
PMID- 27501938
TI - Use of complementary health approaches at military treatment facilities, active
component, U.S. Armed Forces, 2010-2015.
AB - Survey-based research has demonstrated the increasing use and acceptance of
complementary and alternative medicine (CAM) in general and military populations.
This report summarizes the use of three CAM procedures (chiropractic/osteopathic
manipulation, acupuncture, and biofeedback) among active component service
members from 2010 through 2015. Findings document a marked increase in the use of
chiropractic/osteopathic manipulation and acupuncture procedures since 2010. The
majority of the 240 military installations in this analysis provided
chiropractic/osteopathic manipulation; more than three-quarters provided
acupuncture; and approximately one-third provided biofeedback procedures. "Other
and unspecified disorders of the back" was the most frequent condition for which
chiropractic/osteopathic manipulation and acupuncture were used. "Non-allopathic
lesions not elsewhere classified" was the second most frequent diagnosis during
chiropractic/osteopathic manipulation-related visits. The second and third most
frequent diagnoses during acupuncture-related visits were "acute and chronic
pain" and "adjustment reaction," respectively. "Adjustment reaction" was the
second most frequent diagnosis associated with biofeedback. Continued research is
needed to gain a better understanding of why military personnel are using CAM and
the role these procedures play in their health care.
PMID- 27501939
TI - Incident diagnoses of cancers in the active component and cancer-related deaths
in the active and reserve components, U.S. Armed Forces, 2005-2014.
AB - Cancer is the second leading cause of death in the U.S., surpassed only by heart
disease. It is estimated that approximately one of every four deaths in the U.S.
is due to cancer. Between 2005 and 2014 among active component service members in
the U.S. military, crude incidence rates of most cancer diagnoses have remained
relatively stable. During this period, 8,973 active component members were
diagnosed with at least one of the cancers of interest and no specific increasing
or decreasing trends were evident. Cancers accounted for 1,054 deaths of service
members on active duty during the 10-year surveillance period; this included 727
service members in the active component and 327 in the reserve component.
PMID- 27501940
TI - Group-based educational interventions in 11-16-year-olds can be effective in
supporting suboptimal diabetes control.
PMID- 27501941
TI - Using antibiotics responsibly: are we there yet?
AB - Problems of antibiotic access and excess coexist in the world today and are
compounded by rising rates of antibiotic resistance. We introduce two dimensions
of responsibility to this context: responsible individual practices and a broad
societal obligation centered on sustainability. Acting on these responsibilities
requires recognizing the potential tensions between an individual optimum for
antibiotic use and the societal optimum. We relate the tragedy of the commons
metaphor to this situation to illustrate the complexity involved, and we draw on
real-world experiences in Uganda, India, China and France. We conclude that we
must form a global stewardship of antibiotics that can link access, innovation
and conservation efforts across countries to ensure sustainable access to
effective antibiotics for all who need them.
PMID- 27501942
TI - Regulatory Divergence among Beta-Keratin Genes during Bird Evolution.
AB - Feathers, which are mainly composed of alpha- and beta-keratins, are highly
diversified, largely owing to duplication and diversification of beta-keratin
genes during bird evolution. However, little is known about the regulatory
changes that contributed to the expressional diversification of beta-keratin
genes. To address this issue, we studied transcriptomes from five different parts
of chicken contour and flight feathers. From these transcriptomes we inferred
beta-keratin enriched co-expression modules of genes and predicted transcription
factors (TFs) of beta-keratin genes. In total, we predicted 262 TF-target gene
relationships in which 56 TFs regulate 91 beta-keratin genes; we validated 14 of
them by in vitro tests. A dual criterion of TF enrichment and "TF-target gene"
expression correlation identified 26 TFs as the major regulators of beta-keratin
genes. According to our predictions, the ancestral scale and claw beta-keratin
genes have common and unique regulators, whereas most feather beta-keratin genes
show chromosome-wise regulation, distinct from scale and claw beta-keratin genes.
Thus, after expansion from the beta-keratin gene on Chr7 to other chromosomes,
which still shares a TF with scale and claw beta-keratin genes, most feather beta
keratin genes have recruited distinct or chromosome-specific regulators.
Moreover, our data showed correlated gene expression profiles, positive or
negative, between predicted TFs and their target genes over the five studied
feather regions. Therefore, regulatory divergences among feather beta-keratin
genes have contributed to structural differences among different parts of
feathers. Our study sheds light on how feather beta-keratin genes have diverged
in regulation from scale and claw beta-keratin genes and among themselves.
PMID- 27501943
TI - Membrane Proteins Are Dramatically Less Conserved than Water-Soluble Proteins
across the Tree of Life.
AB - Membrane proteins are crucial in transport, signaling, bioenergetics, catalysis,
and as drug targets. Here, we show that membrane proteins have dramatically fewer
detectable orthologs than water-soluble proteins, less than half in most species
analyzed. This sparse distribution could reflect rapid divergence or gene loss.
We find that both mechanisms operate. First, membrane proteins evolve faster than
water-soluble proteins, particularly in their exterior-facing portions. Second,
we demonstrate that predicted ancestral membrane proteins are preferentially lost
compared with water-soluble proteins in closely related species of archaea and
bacteria. These patterns are consistent across the whole tree of life, and in
each of the three domains of archaea, bacteria, and eukaryotes. Our findings
point to a fundamental evolutionary principle: membrane proteins evolve faster
due to stronger adaptive selection in changing environments, whereas cytosolic
proteins are under more stringent purifying selection in the homeostatic interior
of the cell. This effect should be strongest in prokaryotes, weaker in
unicellular eukaryotes (with intracellular membranes), and weakest in
multicellular eukaryotes (with extracellular homeostasis). We demonstrate that
this is indeed the case. Similarly, we show that extracellular water-soluble
proteins exhibit an even stronger pattern of low homology than membrane proteins.
These striking differences in conservation of membrane proteins versus water
soluble proteins have important implications for evolution and medicine.
PMID- 27501944
TI - Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop
Codons to Sense Codons in Condylostoma magnum.
AB - mRNA translation in many ciliates utilizes variant genetic codes where stop
codons are reassigned to specify amino acids. To characterize the repertoire of
ciliate genetic codes, we analyzed ciliate transcriptomes from marine
environments. Using codon substitution frequencies in ciliate protein-coding
genes and their orthologs, we inferred the genetic codes of 24 ciliate species.
Nine did not match genetic code tables currently assigned by NCBI. Surprisingly,
we identified a novel genetic code where all three standard stop codons (TAA,
TAG, and TGA) specify amino acids in Condylostoma magnum We provide evidence
suggesting that the functions of these codons in C. magnum depend on their
location within mRNA. They are decoded as amino acids at internal positions, but
specify translation termination when in close proximity to an mRNA 3' end. The
frequency of stop codons in protein coding sequences of closely related
Climacostomum virens suggests that it may represent a transitory state.
PMID- 27501946
TI - Is it true that plant-derived polyphenols are always beneficial for the human? In
vitro study on Leonurus cardiaca extract properties in the context of the
pathogenesis of Staphylococcus aureus infections.
AB - The aim of the study was to determine whether Leonurus cardiaca L. herb extract
(LCE) used at subinhibitory concentration modifies the characteristics of
Staphylococcus aureus, which is important in the pathogenesis of invasive
infections originating from the bloodstream, in a way favourable for the human
host. Polyphenol-rich LCE, a common ingredient in pharmaceutical products used
for various cardiovascular and nervous system disorders, had shown interesting
antibacterial and antibiofilm properties in our previous studies. Our current
findings indicate that the following S. aureus characteristics decreased,
depending on the LCE concentration: (i) formation of aggregates in plasma, (ii)
adherence to a fibrin-coated surface, (iii) staphylocoagulase-dependent plasma
clotting, (iv) bacterial survival in whole human blood in an ex vivo model, (v)
expression of cell surface protein A and (vi) synthesis of alpha-toxin. However,
staphylococcal tolerance to exogenous hydrogen peroxide was enhanced after pre
incubation with LCE, possibly due to the increased activity of bacterial
antioxidant enzymes, a possibility confirmed by the higher production of
superoxide dismutase and slightly higher production of catalase. The use of LCE
at sub-MIC in in vitro and ex vivo models resulted in the weakening of some
important staphylococcal immunoprotective attributes but the strengthening of
such virulence factors as those responsible for oxidative stress tolerance. Some
of these results and the fact that LCE has direct anticoagulant properties,
reflected in a reduced thrombin-dependent fibrinogen polymerization rate, suggest
a risk of adverse effects, which could be important in the context of S. aureus
survival in the host.
PMID- 27501945
TI - Survival and Evolution of a Large Multidrug Resistance Plasmid in New Clinical
Bacterial Hosts.
AB - Large conjugative plasmids are important drivers of bacterial evolution and
contribute significantly to the dissemination of antibiotic resistance. Although
plasmid borne multidrug resistance is recognized as one of the main challenges in
modern medicine, the adaptive forces shaping the evolution of these plasmids
within pathogenic hosts are poorly understood. Here we study plasmid-host
adaptations following transfer of a 73 kb conjugative multidrug resistance
plasmid to naive clinical isolates of Klebsiella pneumoniae and Escherichia coli.
We use experimental evolution, mathematical modelling and population sequencing
to show that the long-term persistence and molecular integrity of the plasmid is
highly influenced by multiple factors within a 25 kb plasmid region constituting
a host-dependent burden. In the E. coli hosts investigated here, improved plasmid
stability readily evolves via IS26 mediated deletions of costly regions from the
plasmid backbone, effectively expanding the host-range of the plasmid. Although
these adaptations were also beneficial to plasmid persistence in a naive K.
pneumoniae host, they were never observed in this species, indicating that
differential evolvability can limit opportunities of plasmid adaptation. While
insertion sequences are well known to supply plasmids with adaptive traits, our
findings suggest that they also play an important role in plasmid evolution by
maintaining the plasticity necessary to alleviate plasmid-host constrains.
Further, the observed evolutionary strategy consistently followed by all evolved
E. coli lineages exposes a trade-off between horizontal and vertical transmission
that may ultimately limit the dissemination potential of clinical multidrug
resistance plasmids in these hosts.
PMID- 27501947
TI - Fetal Tissues Tested for Microbial Sterility by Culture- and PCR-Based Methods
Can be Safely Used in Clinics.
AB - Cell preparations to be used in clinical practice must be free of infectious
agents. Safety concerns are especially elevated upon the use of human fetal
tissues, which are otherwise highly advantageous in cell therapy. We demonstrate
that treating fetal samples with antibiotic, extensive washing, and
homogenization prior to cryoconservation efficiently removes microbes in general.
Screening a large collection by an automatic culture system showed that 89.2%
fetal tissue samples were sterile, while contamination was detected in 10.8%
samples. Liver and chorion were contaminated more than the brain, kidney, lung,
and soft tissues. Broad-range PCR from the bacterial 16s rRNA gene was adopted as
a confirmatory assay; however, the concordance between the culture-based and PCR
assays was weak. Taxonomic identification was done for contaminated samples by
bacteriological methods and sequencing 16s rRNA PCR products. The two approaches
revealed different spectra of taxonomic groups sharing only Lactobacillus, the
most frequently found genus. In addition, other representatives of vaginal
microbiota were detected by culture-based identification, while PCR product
sequencing has also revealed a subset of nosocomial microorganisms. Importantly,
species known to cause sepsis were identified by both techniques, arguing for
their indispensability and mutual complementarity. We suggest that most
contaminations are taken up during collection of fetal material rather than
originating from an in utero infection. In conclusion, a rigorous microbiological
control by culture and PCR is a prerequisite for safe clinical use of fetal
tissue suspensions.
PMID- 27501948
TI - Commentary: Histaminergic Drugs Could be Novel Targets for Neuroprotection in CNS
Disorders.
PMID- 27501949
TI - Conference Report: 14th International Congress on Amino Acids, Peptides and
Proteins, Vienna, Austria, August 3-7, 2015.
PMID- 27501950
TI - Editorial (Thematic Issue: Old Facts and New Perspectives to Face Alzheimer's
Dementia. Focus on Non Neuronal Participants to Neurodegeneration).
PMID- 27501953
TI - Immediate implant placement and provisionalization in the aesthetic zone using a
flapless or a flap-involving approach: a randomized controlled trial.
AB - AIM: We conducted a randomized controlled trial to compare the effect of flapless
(FLS) or flap-involving (F) immediate placement and provisionalization of single
tooth implants in the aesthetic zone. MATERIALS AND METHODS: Thirty-nine patients
were randomized following extraction of a non-restorable tooth to a FLS or F
group. All implants were immediately placed and provisionalized. We monitored
prospectively changes in the peri-implant mucosal margin, the interproximal bone
and buccal horizontal ridge at 3, 6 and 12 months. RESULTS: At 3 months post
surgery, the mean +/- SD [median (interquartile range)] mesiobuccal peri-implant
gingival margin recession from the pre-surgical soft tissue position amounted to
0.11 +/- 0.32 mm [0 (0, 0.5)] in the FLS treatment arm versus 0.43 +/- 37 mm [0.5
(0, 0.5)] in the F treatment arm (p = 0.02); corresponding values at the
distobuccal surface were 0.11 +/- 32 mm [0 (0, 0)] in the FLS arm versus 0.48 +/-
0.44 mm [0.5 (0, 1)] in the F arm (p = 0.01). No other significant differences in
soft or hard tissue remodelling between the treatment arms were observed at 3, 6
or 12 months. CONCLUSIONS: Flapless and a flap-involving immediate implant
placement and provisionalization in the aesthetic zone resulted in comparable
remodelling of the peri-implant mucosa, interproximal bone and buccal ridge at 6
and 12 months.
PMID- 27501952
TI - S100B Mediates Stemness of Ovarian Cancer Stem-Like Cells Through Inhibiting p53.
AB - S100B is one of the members of the S100 protein family and is involved in the
progression of a variety of cancers. Ovarian cancer is driven by cancer stem-like
cells (CSLCs) that are involved in tumorigenesis, metastasis, chemo-resistance
and relapse. We then hypothesized that S100B might exert pro-tumor effects by
regulating ovarian CSLCs stemness, a key characteristic of CSLCs. First, we
observed the high expression of S100B in ovarian cancer specimens when compared
to that in normal ovary. The S100B upregulation associated with more advanced
tumor stages, poorer differentiation and poorer survival. In addition, elevated
S100B expression correlated with increased expression of stem cell markers
including CD133, Nanog and Oct4. Then, we found that S100B was preferentially
expressed in CD133+ ovarian CSLCs derived from both ovarian cancer cell lines and
primary tumors of patients. More importantly, we revealed that S100B knockdown
suppressed the in vitro self-renewal and in vivo tumorigenicity of ovarian CSLCs
and decreased their expression of stem cell markers. S100B ectopic expression
endowed non-CSLCs with stemness, which has been demonstrated with both in vitro
and in vivo experiments. Mechanically, we demonstrated that the underlying
mechanism of S100B-mediated effects on CSLCs stemness was not dependent on its
binding with a receptor for advanced glycation end products (RAGE), but might be
through intracellular regulation, through the inhibition of p53 expression and
phosphorylation. In conclusion, our results elucidate the importance of S100B in
maintenance of ovarian CSLCs stemness, which might provide a promising
therapeutic target for ovarian cancer. Stem Cells 2017;35:325-336.
PMID- 27501951
TI - Cytosolic phospholipase A2 contributes to innate immune defense against Candida
albicans lung infection.
AB - BACKGROUND: The lung is exposed to airborne fungal spores, and fungi that
colonize the oral cavity such as Candida albicans, but does not develop disease
to opportunistic fungal pathogens unless the immune system is compromised. The
Group IVA cytosolic phospholipase A2 (cPLA2alpha) is activated in response to
Candida albicans infection resulting in the release of arachidonic acid for
eicosanoid production. Although eicosanoids such as prostaglandins and
leukotrienes modulate inflammation and immune responses, the role of cPLA2alpha
and eicosanoids in regulating C. albicans lung infection is not understood.
METHODS: The responses of cPLA2alpha(+/+) and cPLA2alpha(-/-) Balb/c mice to
intratracheal instillation of C. albicans were compared. After challenge, we
evaluated weight loss, organ fungal burden, and the recruitment of cells and the
levels of cytokines and eicosanoids in bronchoalveolar lavage fluid. The ability
of macrophages and neutrophils from cPLA2alpha(+/+) and cPLA2alpha(-/-) mice to
recognize and kill C. albicans was also compared. RESULTS: After C. albicans
instillation, cPLA2alpha(+/+) mice recovered a modest weight loss by 48 h and
completely cleared fungi from the lung by 12 h with no dissemination to the
kidneys. In cPLA2alpha(-/-) mice, weight loss continued for 72 h, C. albicans was
not completely cleared from the lung and disseminated to the kidneys. cPLA2alpha(
/-) mice exhibited greater signs of inflammation including higher neutrophil
influx, and elevated levels of albumin and pro-inflammatory cytokines/chemokines
(IL1alpha, IL1beta, TNFalpha, IL6, CSF2, CXCL1, CCL20) in bronchoalveolar lavage
fluid. The amounts of cysteinyl leukotrienes, thromboxane B2 and prostaglandin E2
were significantly lower in bronchoalveolar lavage fluid from C. albicans
infected cPLA2alpha(-/-) mice compared to cPLA2alpha(+/+) mice. Alveolar
macrophages and neutrophils from uninfected cPLA2alpha(-/-) mice exhibited less
killing of C. albicans in vitro than cells from cPLA2alpha(+/+) mice. In addition
alveolar macrophages from cPLA2alpha(-/-) mice isolated 6 h after instillation of
GFP-C. albicans contained fewer internalized fungi than cPLA2alpha(+/+)
macrophages. CONCLUSIONS: The results demonstrate that cPLA2alpha contributes to
immune surveillance and host defense in the lung to prevent infection by the
commensal fungus C. albicans and to dampen inflammation.
PMID- 27501954
TI - Bibliometric analysis of rheumatology research in the Arab countries.
AB - BACKGROUND: The Arab world has seen an increase in the burden of musculoskeletal
diseases. No bibliometric studies have characterized rheumatology research in the
Arab world. This study evaluates the productivity and impact of rheumatology
research in the Arab world. METHODS: We searched the Web of Science Core
Collection for rheumatology publications, from 1976 to 2014, for each of the Arab
League (AL) countries, North America, Europe and Asia. For the AL countries, the
overall trend of publications and citations was analyzed, while considering the
paper type and collaborations. RESULTS: The AL countries published 944
rheumatology papers over the period studied. The number of publications increased
by a factor of 2.77 (95 % CI, 2.75-2.78) each decade, and citations increased by
a factor of 2.36 (95 % CI, 0.96-5.82). The absolute number of papers included in
the top-10 rheumatology journals remained constant but the proportion decreased.
Papers involving collaboration among AL countries were found to increase over
time. CONCLUSIONS: Overall, the AL countries lag in research productivity and
impact compared to other regions. Three countries are responsible for the
majority of publications, while four countries receive the majority of citations.
PMID- 27501955
TI - Determination of GP88 (progranulin) expression in breast tumor biopsies improves
the risk predictive value of the Nottingham Prognostic Index.
AB - BACKGROUND: The Nottingham Prognostic Index (NPI), which combines numerical
values for nodal status, tumor size and histological grade, is used in the
standard of care to provide predictive value information on post-surgery survival
for patients with primary breast cancer. Attempts to improve the performance of
the NPI algorithm have been carried out by testing the inclusion of other
biomarker expression and morphological features such as vascular invasion. In the
present study, we investigated whether expression of the autocrine growth and
survival factor GP88 (progranulin), known to be overexpressed in breast cancer,
would improve NPI's predictive value. METHODS: We examined by
immunohistochemistry (IHC) the GP88 expression in 508 cases of estrogen receptor
positive invasive ductal carcinoma with known clinical outcomes and for which NPI
had been determined. GP88 IHC expression was scored by two board certified
pathologists and classified into two score groups of GP88 <3+ (0, 1+, 2+) and
GP88 = 3+. The correlation between GP88 scoring, NPI and disease-free (DFS) or
overall survival (OS) outcomes was then examined by Kaplan-Meier analysis, Cox
proportional Hazard (CPH) ratio and Pearson's X (2) test. RESULTS: Kaplan-Meier
survival graphs of cases categorized by their NPI scores (<3.4, 3.4-5.4, >5.4)
and GP88 expression showed that for patients within the same NPI subgroup,
patients having tumors with a high GP88 expression (GP88 IHC score of 3+) had a
worse DFS than patients with tumors that had a low GP88 expression (GP88 IHC
score <3+). When adjusted for NPI, high GP88 score was significantly associated
with recurrence with a hazard ratio of 3.30 (95 % CI 2.12 to 5.14). CONCLUSIONS:
The data suggest that the determination of GP88 tumor expression at time of
diagnosis for early stage breast cancer patients can provide additional survival
information to that provided by NPI alone and thus may be useful for risk
management of patients diagnosed with breast cancer.
PMID- 27501956
TI - The leishmanicidal activity of oleuropein is selectively regulated through
inflammation- and oxidative stress-related genes.
AB - BACKGROUND: Much research effort has been focused on investigating new compounds
derived from low-cost sources, such as natural products, for treating
leishmaniasis. Oleuropein derived from numerous plants, particularly from the
olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological
activities. Our previous findings showed that oleuropein exhibits leishmanicidal
effects against three Leishmania spp. in vitro, and minimizes the parasite burden
in L. donovani-infected BALB/c mice. The aim of the present study is to
investigate the possible mechanism(s) that mediate this leishmanicidal activity.
METHODS: We determined the efficacy of oleuropein in elevating ROS and NO
production in L. donovani-infected J774A.1 macrophages and in explanted
splenocytes and hepatocytes obtained from L. donovani-infected BALB/c mice. We
also assessed the expression of genes that are related to inflammation, T-cell
polarization and antioxidant defense, in splenocytes. Finally, we determined the
ratios of specific IgG2a/IgG1 antibodies and DTH reactions in L. donovani
infected BALB/c mice treated with oleuropein. RESULTS: Oleuropein was able to
elevate ROS production in both in vitro and in vivo models of visceral
leishmaniasis and raised NO production in ex vivo cultures of splenocytes and
hepatocytes. The extensive oxidative stress found in oleuropein-treated mice was
obviated by the upregulation of the host's antioxidant enzyme (mGCLC) and the
simultaneous downregulation of the corresponding enzyme of the parasite (LdGCLC).
Moreover, oleuropein was able to mount a significant Th1 polarization
characterized by the expression of immune genes (IL-12beta, IL-10, TGF-beta1, IFN
gamma) and transcription factors (Tbx21 and GATA3). Moreover, this
immunomodulatory effect was also correlated with an inhibitory effect on IL-1beta
gene expression, rather than with the expression of IL-1alpha, IL-1rn and TNF
alpha. Furthermore, oleuropein-treated BALB/c mice mounted a delayed-type
hypersensitivity (DTH) response and an elevated Leishmania-specific IgG2a/IgG1
ratio that clearly demonstrated an in vivo protective mechanism. CONCLUSION: The
ability of Oleuropein to promote a Th1 type immune response in L. donovani
infected BALB/c mice points towards the candidacy of this bioactive compound as
an immunomodulatory agent that may complement therapeutic approaches to
leishmaniasis.
PMID- 27501957
TI - Preclinical anaylses of [18F]cEFQ as a PET tracer for imaging metabotropic
glutamate receptor type 1 (mGluR1).
AB - Metabotropic glutamate receptor type 1 (mGluR1) is related with various
neurological and psychiatric diseases, such as anxiety, depression, epilepsy,
Parkinson's disease, and neuropathic pain. Hence, mGluR1 is an important target
for drug development and imaging. We synthesized [18F]cEFQ (3-ethyl-2
[18F]fluoroquinolin-6-yl cis-(4-methoxycyclohexyl)methanone) as a PET tracer for
selective mGluR1 imaging and evaluated its properties in rodents. A
chloroquinoline precursor was labeled by a nucleophilic substitution reaction,
and the resulting [18F]cEFQ was obtained with high radiochemical purity (>99%)
and specific activity (63-246 GBq/umol). The log D value was 3.24, and the
initial brain uptake at 10 min was over 4% of injected dose per gram in BALB/c
mice. According to PET/CT and autoradiography in SD rats, [18F]cEFQ showed wide
distribution in the whole brain and the highest uptake in the cerebellum. Pre
treatment with unlabeled cEFQ or the mGluR1-specific antagonist JNJ16259685
blocked the uptake of [18F]cEFQ. However, the uptake was not blocked by pre
treatment with the mGluR5-specific antagonist ABP688. The trans isomer [18F]tEFQ
did not show high uptake in the mGluR1-rich region. [18F]cEFQ was
straightforwardly prepared using a chloro-derivative precursor. Its feasibility
as a specific and selective PET agent for imaging mGluR1 was proved by in vitro
and in vivo experiments using rodents.
PMID- 27501958
TI - Bone tissue response to experimental zirconia implants.
AB - OBJECTIVES: This study seeks to assess the bone tissue response at experimental
zirconia implants in comparison with titanium implants by means of descriptive
histology and histomorphometry in a dog model. MATERIALS AND METHODS:
Experimental zirconia implants with three different surface roughnesses (Z1 < Z2
< Z3) and conventional sandblasted large grit and acid-etched titanium implants
were inserted bilaterally in the lower jaws of nine beagle dogs. Tissue biopsies
were obtained after 3 and 14 days and 10 weeks of transmucosal healing. The
tissue response was investigated by assessing new, old, and total bone-to-implant
contact (nBIC, oBIC, and tBIC). RESULTS: After 3 days, histological specimens of
all groups showed an intimate contact between the implant threads and pristine
bone (tBIC: Ti 42.3 % > Z2 30.1 % > Z3 28.9 % > Z1 25.1 %, p > 0.05, unpaired t
test, respectively). A provisional matrix was evident at all implant surfaces. At
14 days, percentages of BIC increased in all groups (tBIC: Ti 62.1 % > Z3 69.2 %
< Z2 44.4 % > Z1 42.3 %; nBIC: Z3 58.9 % > Ti 52.2 % > Z2 35.1 % > Z1 32.5 %).
Two implants, one of group Z1 and one of group Z2, were lost. At 10 weeks, 13 of
18 zirconia implants were lost, equally distributed between all three surface
modifications. The remaining implants revealed increased BIC values (tBIC: Z3
69.5 % > Ti 58.5 % > Z1 49.7 % > Z2 37.1 %; nBIC: Z3 57.2 % > Ti 46.5 % > Z1 32.3
% > Z2 29.3 %). Histomorphometrical analysis showed comparable mean BIC values in
all groups at all healing periods without showing statistical differences (p >
0.05, unpaired t test, respectively). CONCLUSION: The bone tissue response
throughout the healing periods was characterized by a constant bone remodeling
accompanied by resorption of old bone in favor of new bone formation at both
titanium and zirconia implants. Surface roughness had a positive effect on BIC,
although not showing statistical significance. Due to the poor survival rate, the
experimental zirconia implants investigated may not be suitable for clinical use.
CLINICAL RELEVANCE: Zirconia has been introduced as an alternative biomaterial
for dental implants. A profound knowledge about the bone tissue response at
zirconia implant surfaces is necessary as it plays an important role for proper
osseointegration and long-term stability.
PMID- 27501959
TI - Risk factors associated with early mortality in patients with multiple myeloma
who were treated upfront with a novel agents containing regimen.
AB - BACKGROUND: Although the introduction of novel agents improved the survival
outcomes in patients with multiple myeloma (MM), some patients died within one
year (early mortality, EM) following diagnosis. In this study, we evaluated the
EM rate, and investigated the risk factors associated with EM in MM patients.
METHODS: Retrospective data from 542 patients who were initially treated with a
novel agent-containing regimen were analyzed. RESULTS: The median overall
survival (OS) for the entire cohort was 56.5 months. The median OS in the 2010
2014 group was longer than in the 2002-2009 group (59.2 months vs. 49.1 months, P
= 0.054). The rate of EM was 13.8 %, and the most common causes of EM were
infection and comorbidity. In multivariate analysis, the age-adjusted Charlson
comorbidity index (ACCI >= 4), low body mass index (BMI < 20 kg/m(2)),
thrombocytopenia, and renal failure were significantly associated with EM. The
presence of none, 1, or >= 2 factors was associated with a 4.1 %, 14.3 %, or 27.4
% risk of EM (P < 0.001), respectively. The median OS times were significantly
different depending on the presence of factors associated with EM (P < 0.001).
CONCLUSIONS: In conclusion, the ACCI (>= 4), low BMI, thrombocytopenia and renal
failure were strong predictors for EM in the novel agent era. The results of this
study will help to identify patients at high risk for EM, and may be helpful to
more accurately predict prognosis of MM patients in the novel-agent era.
PMID- 27501961
TI - Beyond the Drama: the Beautiful Life in News Feeds on Cancer.
AB - Facebook is one of the main communication tools in the world nowadays. In Brazil,
it is used for almost half of the population. Knowing what is conveyed about
cancer by this social network can be an important step for the development of
efficient health communication strategies. We evaluate Facebook user's comments
on pages about cancer; verify if there is a pattern of public awareness on the
disease and compare it with results from other studies. Three pages about cancer
on Facebook were selected among those with more followers in Brazil. For 6
months, from January to June 2014, all posts were selected and evaluated, and we
created eight categories. On each page, the categories that generated most
comments were elected for the second analysis. The behavior of empowered citizens
by new communication tools is the target of this study. Similarities and
differences between 12,926 comments coming from 1243 posts in three different
Facebook pages on cancer were analyzed. Four new categories were identified:
"religion," "positive," "negative," and "information." Despite the differences
among the three pages selected for this study, we observed the predominance of
positive speeches associated with religious terms. Following public perceptions
on cancer is an important step for the development of efficient health
communication strategies.
PMID- 27501960
TI - Pregnancy and multiple sclerosis: from molecular mechanisms to clinical
application.
AB - Translational research generally refers to a "bench to bedside" approach where
basic science discoveries in models move to clinical trials in humans. However, a
"bedside to bench to bedside" approach may be more promising with respect to
clinical relevance, since it starts with a clinical observation that can serve as
a research paradigm to elucidate mechanisms and translate them back into novel
therapeutic approaches. The effect of pregnancy on human autoimmune disorders in
general, and multiple sclerosis (MS) in particular, serves as an intriguing
example of how this can be used to understand disease pathobiology and discover
new therapeutic targets. Disease activity in MS undergoes pronounced shifts in
the time before, during, and after pregnancy. The most well-known and established
example is a reduction in relapse rates in the last trimester by 70-80 %.
However, disease activity reappears in the first few months after delivery,
temporarily overshooting pre-pregnancy levels. This phenomenon has since its
first description served as a model for investigating novel treatment options in
animal models and has cumulated in successful phase 2a and 2b trials in female MS
patients. However, recently, a number of other clinical observations have been
made that might be similarly suitable to offer additional insights into
pathobiological mechanisms of MS activity, progression, and possibly even
incidence. Here, we outline the various changes in the clinical course of MS that
have been described in relation to pregnancy, both short term and long term, and
discuss how these may inform the development of novel treatments for autoimmune
diseases.
PMID- 27501962
TI - Material deprivation and health: a longitudinal study.
AB - BACKGROUND: Does material deprivation affect the consequences of ill health?
Answering this question requires that we move beyond the effects of income.
Longitudinal data on material deprivation, longstanding illness and limiting
longstanding illness enables investigations of the effects of material
deprivation on risk of limiting longstanding illness. This study investigates
whether a shift from affording to not affording a car predicts the probability of
limiting longstanding ill (LLSI). METHODS: The 2008-2011 longitudinal panel of
Statistics on Income, Social Inclusion and Living Conditions (EU-SILC) is
utilised. Longitudinal fixed effects logit models are applied, using LLSI as
dependent variable. Transition from affording a car to not affording a car is
used as a proxy for material deprivation. All models are controlled for whether
the person becomes longstanding ill (LSI) as well as other time-variant
covariates that could affect the results. RESULTS: The analysis shows a
statistically significant increased odds ratio of LLSI when individuals no longer
can afford a car, after controlling for confounders and LSI in the previous year
(1.129, CI = 1.022-1.248). However, when restricting the sample to observations
where respondents report longstanding illness the results are no longer
significant (1.032, CI = 0.910-1.171). CONCLUSION: The results indicate an
individual level effect of material deprivation on LLSI, suggesting that material
resources can affect the consequences of ill health.
PMID- 27501963
TI - Orthokeratinized Odontogenic Cyst with an Associated Keratocystic Odontogenic
Tumor Component and Ghost Cell Keratinization and Calcifications in a Patient
with Gardner Syndrome.
AB - Gardner syndrome (GS) is caused by mutations in the APC and besides adenomatous
colorectal polyps includes such manifestations as osteomas, epidermoid cysts
(ECs) and occasionally multiple pilomatricomas. More than 50 % of ECs in patients
with GS exhibit pilomatricoma-like ghost cell keratinization. The latter may be
explained by the fact that the development of both GS and pilomatricoma is driven
by activation of the Wnt/beta-catenin signaling pathway. A 62-year-old, Caucasian
male with history of GS presented with a unilocular, mixed radiopaque/radiolucent
mandibular lesion causing divergence and external root resorption of involved
teeth. Histopathologically, the lesion was composed of two cystic components, an
orthokeratinized odontogenic cyst (OOC) and a smaller one with characteristics of
keratocystic odontogenic tumor (KCOT) featuring, focally, ghost cells and an
epithelial morule-like structure. Dystrophic calcifications essentially similar
to those seen in pilomatricomas were observed in the fibrous connective tissue
wall. The KCOT and OOC epithelia revealed strong and diffuse cytokeratin
(AE1/AE3) and beta-catenin immunoreactivity. CD10 positive immunostaining was
seen in the keratin and superficial spinous cell layers in both OOC and KCOT. The
intraepithelial and mural ghost cells showed a cytokeratin (+), beta-catenin and
CD10 (-) immunophenotype. The diagnosis of OOC with ghost cell calcifications in
association with KCOT was rendered. The patient was lost to follow-up. Although a
coincidental co-existence cannot be excluded, ghost cell calcifications mimicking
pilomatricoma-like changes in an unusual odontogenic cyst combining OOC and KCOT
features as seen in this patient with GS may be explained by the common molecular
mechanisms underlying the pathogenesis of cutaneous pilomatricomas and GS.
PMID- 27501964
TI - MASCC/ESMO Antiemetic Guidelines: Introduction to the 2016 guideline update.
PMID- 27501965
TI - 2016 Updated MASCC/ESMO consensus recommendations: Emetic risk classification and
evaluation of the emetogenicity of antineoplastic agents.
AB - PURPOSE: Employing the same framework as in previous guideline updates,
antineoplastic agents were classified into four emetic risk categories. The
classification of the emetogenic level of new antineoplastic agents, especially
for the oral drugs, represents an increasing challenge. Accurate reporting of
emetogenicity of new antineoplastic agents in the absence of preventive
antiemetic treatment is rarely available. METHODS: A systematic search was
conducted for drugs approved after 2009 until June 2015 using EMBASE and PubMed.
The search term was "drug name." The restrictions were language (English records
only), date (2009 to 2015), and level of evidence ("clinical trial"). RESULTS:
From January 2009 to June 2015, 42 new antineoplastic agents were identified and
a systematic search was conducted to identify relevant studies to help define
emetic risk levels. The reported incidence of vomiting varied across studies for
many agents, but there was adequate evidence to allow 41 of the 42 new
antineoplastic agents to be classified according to emetogenic risk. No highly
emetogenic agents were identified. Seven moderately emetogenic agents, 26 low
emetogenic, agents and eight minimal emetogenic agents were identified and
classified accordingly. The MASCC/ESMO update committee also recommended
reclassification of the combination of an anthracycline and cyclophosphamide (AC)
as highly emetogenic. CONCLUSION: Despite several limitations, we have attempted
to provide a reasonable approximation of the emetic risk associated with new
antineoplastic agents through a comprehensive search of the available literature.
Hopefully by the next update, more precise information on emetic risk will have
been collected during new agent development process.
PMID- 27501966
TI - Efficacy and safety of lipegfilgrastim compared with placebo in patients with non
small cell lung cancer receiving chemotherapy: post hoc analysis of elderly
versus younger patients.
AB - PURPOSE: Lipegfilgrastim, a glycoPEGylated recombinant granulocyte colony
stimulating factor (G-CSF), reduces neutropenia duration and febrile neutropenia
(FN) incidence in patients with cancer receiving myelosuppressive chemotherapy. A
phase 3 trial of lipegfilgrastim was conducted in patients with advanced non
small cell lung cancer (NSCLC) receiving cisplatin/etoposide (which produces mild
to-moderate myelosuppression). Because patients aged >65 years are at higher risk
for FN versus younger patients, this post hoc analysis compared outcomes in
elderly (>65 years) versus younger participants in this trial. METHODS: Patients
were randomized 2:1 to receive a once-per-cycle single subcutaneous injection of
lipegfilgrastim 6 mg or placebo, with up to 4 cycles of every-3-week cisplatin
(day 1) and etoposide (days 1-3). The primary end point was FN incidence during
cycle 1. Outcomes were compared across treatment groups and by age groups (<=65
and >65 years). RESULTS: For patients aged <=65 years, FN incidence during cycle
1 was similar in the lipegfilgrastim and placebo groups (3.0 vs 3.2 %,
respectively), whereas for elderly patients, there was a reduction in FN
incidence with lipegfilgrastim (0 vs 13.3 %, respectively). In both age
subgroups, lipegfilgrastim showed a propensity to reduce the incidence and
duration of severe neutropenia, time to absolute neutrophil count (ANC) recovery,
and depth of ANC nadir. Adverse events were generally similar between groups.
CONCLUSIONS: This analysis suggests that in patients with a higher FN risk, such
as the elderly patients of this study, lipegfilgrastim reduces not only the
duration of severe neutropenia but also the incidence of FN.
PMID- 27501967
TI - The influence hydrogen atom addition has on charge switching during motion of the
metal atom in endohedral Ca@C60H4 isomers.
AB - Density functional theory has been applied in a study of charge transfer between
an endohedral calcium atom and the fullerene cage in Ca@C60H4 and [Ca@C60H4](+)
isomers. Previous calculations on Ca@C60 have shown that the motion of calcium
within a fullerene is accompanied by large changes in electron density on the
carbon cage. Based on this observation, it has been proposed that a tethered
endohedral fullerene might form the bases of a nanoswitch. Through the addition
of hydrogen atoms to one hemisphere of the cage it is shown that, when compared
with Ca@C60, asymmetric and significantly reduced energy barriers can be
generated with respect to motion of the calcium atom. It is proposed that
hydrogen atom addition to a fullerene might offer a route for creating a bi
stable nanoswitch that can be fine-tuned through the selection of an appropriate
isomer and number of atoms attached to the cage of an endohedral fullerene.This
article is part of the themed issue 'Fullerenes: past, present and future,
celebrating the 30th anniversary of Buckminster Fullerene'.
PMID- 27501968
TI - The Stone-Wales transformation: from fullerenes to graphite, from radiation
damage to heat capacity.
AB - The Stone-Wales (SW) transformation, or carbon-bond rotation, has been
fundamental to understanding fullerene growth and stability, and ab initio
calculations show it to be a high-energy process. The nature and topology of the
fullerene energy landscape shows how the Ih-C60 must be the final product, if SW
transformations are fast enough, and various mechanisms for their catalysis have
been proposed. We review SW transformations in fullerenes and then discuss the
analogous transformation in graphite, where they form the Dienes defect,
originally posited to be a transition state in the direct exchange of a bonded
atom pair. On the basis of density functional theory calculations in the local
density approximation, we propose that non-equilibrium concentrations of the
Dienes defect arising from displacing radiation are rapidly healed by point
defects and that equilibrium concentrations of Dienes defects are responsible for
the divergent ultra-high-temperature heat capacity of graphite.This article is
part of the themed issue 'Fullerenes: past, present and future, celebrating the
30th anniversary of Buckminster Fullerene'.
PMID- 27501970
TI - Super-atom molecular orbital excited states of fullerenes.
AB - Super-atom molecular orbitals are orbitals that form diffuse hydrogenic excited
electronic states of fullerenes with their electron density centred at the centre
of the hollow carbon cage and a significant electron density inside the cage.
This is a consequence of the high symmetry and hollow structure of the molecules
and distinguishes them from typical low-lying molecular Rydberg states. This
review summarizes the current experimental and theoretical studies related to
these exotic excited electronic states with emphasis on femtosecond photoelectron
spectroscopy experiments on gas-phase fullerenes.This article is part of the
themed issue 'Fullerenes: past, present and future, celebrating the 30th
anniversary of Buckminster Fullerene'.
PMID- 27501969
TI - Two-dimensional inorganic analogues of graphene: transition metal
dichalcogenides.
AB - The discovery of graphene marks a major event in the physics and chemistry of
materials. The amazing properties of this two-dimensional (2D) material have
prompted research on other 2D layered materials, of which layered transition
metal dichalcogenides (TMDCs) are important members. Single-layer and few-layer
TMDCs have been synthesized and characterized. They possess a wide range of
properties many of which have not been known hitherto. A typical example of such
materials is MoS2 In this article, we briefly present various aspects of layered
analogues of graphene as exemplified by TMDCs. The discussion includes not only
synthesis and characterization, but also various properties and phenomena
exhibited by the TMDCs.This article is part of the themed issue 'Fullerenes:
past, present and future, celebrating the 30th anniversary of Buckminster
Fullerene'.
PMID- 27501971
TI - Unconventional high-Tc superconductivity in fullerides.
AB - A3C60 molecular superconductors share a common electronic phase diagram with
unconventional high-temperature superconductors such as the cuprates:
superconductivity emerges from an antiferromagnetic strongly correlated Mott
insulating state upon tuning a parameter such as pressure (bandwidth control)
accompanied by a dome-shaped dependence of the critical temperature, Tc However,
unlike atom-based superconductors, the parent state from which superconductivity
emerges solely by changing an electronic parameter-the overlap between the outer
wave functions of the constituent molecules-is controlled by the C60 (3-)
molecular electronic structure via the on-molecule Jahn-Teller effect influence
of molecular geometry and spin state. Destruction of the parent Mott-Jahn-Teller
state through chemical or physical pressurization yields an unconventional Jahn
Teller metal, where quasi-localized and itinerant electron behaviours coexist.
Localized features gradually disappear with lattice contraction and conventional
Fermi liquid behaviour is recovered. The nature of the underlying (correlated
versus weak-coupling Bardeen-Cooper-Schrieffer theory) s-wave superconducting
states mirrors the unconventional/conventional metal dichotomy: the highest
superconducting critical temperature occurs at the crossover between Jahn-Teller
and Fermi liquid metal when the Jahn-Teller distortion melts.This article is part
of the themed issue 'Fullerenes: past, present and future, celebrating the 30th
anniversary of Buckminster Fullerene'.
PMID- 27501972
TI - Fullerene ion chemistry: a journey of discovery and achievement.
AB - An account is provided of the extraordinary features of buckminster fullerene
cations and their chemistry that we discovered in our Ion Chemistry Laboratory at
York University (Canada) during a 'golden' period of research in the early 1990s,
just after C60 powder became available. We identified new chemical ways of C60
ionization and tracked novel chemistry of C60 (n+) as a function of charge state
(n=1-3) with some 50 different reagent molecules. We found that multiple charges
enhance reaction rates and diversify reaction products and mechanisms. Strong
electrostatic interactions with reagent molecules were seen to reduce barriers to
carbon surface bonding and charge-separation reactions, while intramolecular
Coulomb repulsion appeared to localize charge on the surface or the substituent
and so influence higher order chemistry, including 'spindle', 'star', 'fuzzy
ball', 'ball-and-chain' and dimer ion formation. We introduced the notion of
'apparent' gas-phase acidity with measurements of proton-transfer reactions of
multiply charged fullerene cations. We also explored the attachment of atomic
metal cations to C60 and their subsequent reactions. All these findings were
applied to the possible chemistry of fullerene cations in the interstellar medium
with a focus on multiply charged fullerene ion formation and the intervention of
fullerene cations in fullerene derivatization and molecular synthesis, with a
view to their possible future detection.This article is part of the themed issue
'Fullerenes: past, present and future, celebrating the 30th anniversary of
Buckminster Fullerene'.
PMID- 27501973
TI - Another big discovery-metallofullerenes.
AB - Several days after the first experimental observation of the 'magic number'
soccerball-shaped C60 in a laser-vaporized cluster beam mass spectrum by Kroto
and co-workers (Heath et al 1985 J. Am. Chem. Soc. 107, 7779-7780.
(doi:10.1021/ja00311a102)) they also found a magic number feature owing to La@C60
in a mass spectrum prepared by laser vaporization of a LaCl3-impregnated graphite
rod. With the advent of macroscopic synthesis and the following successful
separation and purification of metallofullerenes, both experimental and
theoretical studies of metallofullerenes have developed quite rapidly to date so
as to elucidate their structural, electronic, magnetic and transport properties.
Furthermore, a bottom-up closed network growth mechanism has experimentally been
shown to play a crucial role in generating various types of
metallofullerenes.This article is part of the themed issue 'Fullerenes: past,
present and future, celebrating the 30th anniversary of Buckminster Fullerene'.
PMID- 27501974
TI - Fullerene and nanotube growth: new insights using first principles and molecular
dynamics.
AB - Shortly after the discovery of fullerenes, many researchers pointed out that
carbon nanotubes could be considered as elongated fullerenes. However, the
detailed formation mechanism for both structures has been a topic of debate for
several years, and consequently it has been difficult to draw a clear connection
between the two systems. While the synthesis conditions appear to be different
for both fullerenes and nanotubes, here, we demonstrate that it is highly likely
that, at an initial growth stage, single-walled carbon nanotubes begin to grow
from a hemisphere-like fullerene cap. More importantly, by analysing the minimum
energy path, it is shown that the insertion of C2 fragments drives the
transformation of this fullerene cap into an elongated structure that leads to
the formation of very short carbon nanotubes.This article is part of the themed
issue 'Fullerenes: past, present and future, celebrating the 30th anniversary of
Buckminster Fullerene'.
PMID- 27501975
TI - Ab initio infrared vibrational modes for neutral and charged small fullerenes
(C20, C24, C26, C28, C30 and C60).
AB - We calculate the infrared (IR) absorption spectra using DFT B3LYP(6-311G) for a
range of small closed-cage fullerenes, Cn, n=20, 24, 26, 28, 30 and 60, in both
neutral and multiple positive and negative charge states. The results are of use,
notably, for direct comparison with observed IR absorption in the interstellar
medium. Frequencies fall typically into two ranges, with C-C stretch modes around
1100-1500 cm(-1) (6.7-9.1 MUm) and fullerene-specific radial motion associated
with under-coordinated carbon at pentagonal sites in the range 600-800 cm(-1)
(12.5-16.7 MUm). Notably, negatively charged fullerenes show significantly
stronger absorption intensities than neutral species. The results suggest that
small cage fullerenes, and notably metallic endofullerenes, may be responsible
for many of the unassigned interstellar IR spectral lines.This article is part of
the themed issue 'Fullerenes: past, present and future, celebrating the 30th
anniversary of Buckminster Fullerene'.
PMID- 27501976
TI - Pathway to the identification of C60+ in diffuse interstellar clouds.
AB - The origin of the attenuation of starlight in diffuse clouds in interstellar
space at specific wavelengths ranging from the visible to the near-infrared has
been unknown since the first astronomical observations around a century ago. The
absorption features, termed the diffuse interstellar bands, have subsequently
been the subject of much research. Earlier this year four of these interstellar
bands were shown to be due to the absorption by cold, gas phase [Formula: see
text] molecules. This discovery provides the first answer to the problem of the
diffuse interstellar bands and leads naturally to fascinating questions regarding
the role of fullerenes and derivatives in interstellar chemistry. Here, we review
the identification process placing special emphasis on the laboratory studies
which have enabled spectroscopic measurement of large cations cooled to
temperatures prevailing in the interstellar medium.This article is part of the
themed issue 'Fullerenes: past, present and future, celebrating the 30th
anniversary of Buckminster Fullerene'.
PMID- 27501977
TI - Professor Sir Harry Kroto (1939-2016).
PMID- 27501978
TI - Fullerenes: past, present and future, celebrating the 30th anniversary of
Buckminster Fullerene.
PMID- 27501979
TI - Morphology and Photoluminescence of HfO2Obtained by Microwave-Hydrothermal.
AB - In this letter, we report on the obtention of hafnium oxide (HfO2) nanostructures
by the microwave-hydrothermal method. These nanostructures were analyzed by X-ray
diffraction (XRD), field-emission gum scanning electron microscopy (FEG-SEM),
transmission electron microscopy (TEM), energy dispersive X-ray spectrometry
(EDXS), ultraviolet-visible (UV-vis) spectroscopy, and photoluminescence (PL)
measurements. XRD patterns confirmed that this material crystallizes in a
monoclinic structure. FEG-SEM and TEM micrographs indicated that the rice-like
morphologies were formed due to an increase in the effective collisions between
the nanoparticles during the MH processing. The EDXS spectrum was used to verify
the chemical compositional of this oxide. UV-vis spectrum revealed that this
material have an indirect optical band gap. When excited with 488 nm wavelength
at room temperature, the HfO2nanostructures exhibited only one broad PL band with
a maximum at around 548 nm (green emission).
PMID- 27501980
TI - Role of the ganSPQAB Operon in Degradation of Galactan by Bacillus subtilis.
AB - Bacillus subtilis possesses different enzymes for the utilization of plant cell
wall polysaccharides. This includes a gene cluster containing galactan
degradation genes (ganA and ganB), two transporter component genes (ganQ and
ganP), and the sugar-binding lipoprotein-encoding gene ganS (previously known as
cycB). These genes form an operon that is regulated by GanR. The degradation of
galactan by B. subtilis begins with the activity of extracellular GanB. GanB is
an endo-beta-1,4-galactanase and is a member of glycoside hydrolase (GH) family
53. This enzyme was active on high-molecular-weight arabinose-free galactan and
mainly produced galactotetraose as well as galactotriose and galactobiose. These
galacto-oligosaccharides may enter the cell via the GanQP transmembrane proteins
of the galactan ABC transporter. The specificity of the galactan ABC transporter
depends on the sugar-binding lipoprotein, GanS. Purified GanS was shown to bind
galactotetraose and galactotriose using thermal shift assay. The energy for this
transport is provided by MsmX, an ATP-binding protein. The transported galacto
oligosaccharides are further degraded by GanA. GanA is a beta-galactosidase that
belongs to GH family 42. The GanA enzyme was able to hydrolyze short-chain beta
1,4-galacto-oligosaccharides as well as synthetic beta-galactopyranosides into
galactose. Thermal shift assay as well as electrophoretic mobility shift assay
demonstrated that galactobiose is the inducer of the galactan operon regulated by
GanR. DNase I footprinting revealed that the GanR protein binds to an operator
overlapping the -35 box of the sigma(A)-type promoter of Pgan, which is located
upstream of ganS IMPORTANCE: Bacillus subtilis is a Gram-positive soil bacterium
that utilizes different types of carbohydrates, such as pectin, as carbon
sources. So far, most of the pectin degradation systems and enzymes have been
thoroughly studied in B. subtilis Nevertheless, the B. subtilis utilization
system of galactan, which is found as the side chain of the rhamnogalacturonan
type I complex in pectin, has remained partially studied. Here, we investigated
the galactan utilization system consisting of the ganSPQAB operon and its
regulator ganR This study improves our knowledge of the carbohydrate degradation
systems of B. subtilis, especially the pectin degradation systems. Moreover, the
galactan-degrading enzymes may be exploited for the production of galacto
oligosaccharides, which are used as prebiotic substances in the food industry.
PMID- 27501981
TI - Transcriptomic and Phenotypic Analysis Reveals New Functions for the Tat Pathway
in Yersinia pseudotuberculosis.
AB - The twin-arginine translocation (Tat) system mediates the secretion of folded
proteins that are identified via an N-terminal signal peptide in bacteria,
plants, and archaea. Tat systems are associated with virulence in many bacterial
pathogens, and our previous studies revealed that Tat-deficient Yersinia
pseudotuberculosis was severely attenuated for virulence. Aiming to identify Tat
dependent pathways and phenotypes of relevance for in vivo infection, we analyzed
the global transcriptome of parental and DeltatatC mutant strains of Y.
pseudotuberculosis during exponential and stationary growth at 26 degrees C and
37 degrees C. The most significant changes in the transcriptome of the DeltatatC
mutant were seen at 26 degrees C during stationary-phase growth, and these
included the altered expression of genes related to virulence, stress responses,
and metabolism. Subsequent phenotypic analysis based on these transcriptome
changes revealed several novel Tat-dependent phenotypes, including decreased YadA
expression, impaired growth under iron-limited and high-copper conditions, as
well as acidic pH and SDS. Several functionally related Tat substrates were also
verified to contribute to these phenotypes. Interestingly, the phenotypic defects
observed in the Tat-deficient strain were generally more pronounced than those in
mutants lacking the Tat substrate predicted to contribute to that specific
function. Altogether, this provides new insight into the impact of Tat deficiency
on in vivo fitness and survival/replication of Y. pseudotuberculosis during
infection. IMPORTANCE: In addition to its established role in mediating the
secretion of housekeeping enzymes, the Tat system has been recognized as being
involved in infection. In some clinically relevant bacteria, such as Pseudomonas
spp., several key virulence determinants can readily be identified among the Tat
substrates. In enteropathogens, such as Yersinia spp., there are no obvious
virulence determinants among the Tat substrates. Tat mutants show no growth
defect in vitro but are highly attenuated in in vivo This makes Tat an attractive
target for the development of novel antimicrobials. Therefore, it is important to
establish the causes of the attenuation. Here, we show that the attenuation is
likely due to synergistic effects of different Tat-dependent phenotypes that each
contributes to lowered in vivo fitness.
PMID- 27501982
TI - A Synonymous Mutation Upstream of the Gene Encoding a Weak-Link Enzyme Causes an
Ultrasensitive Response in Growth Rate.
AB - When microbes are faced with an environmental challenge or opportunity,
preexisting enzymes with promiscuous secondary activities can be recruited to
provide newly important functions. Mutations that increase the efficiency of a
new activity often compromise the original activity, resulting in an inefficient
bifunctional enzyme. We have investigated the mechanisms by which growth of
Escherichia coli can be improved when fitness is limited by such an enzyme, E383A
ProA (ProA*). ProA* can serve the functions of both ProA (required for synthesis
of proline) and ArgC (required for synthesis of arginine), albeit poorly. We
identified four genetic changes that improve the growth rate by up to 6.2-fold.
Two point mutations in the promoter of the proBA* operon increase expression of
the entire operon. Massive amplification of a genomic segment around the proBA*
operon also increases expression of the entire operon. Finally, a synonymous
point mutation in the coding region of proB creates a new promoter for proA* This
synonymous mutation increases the level of ProA* by 2-fold but increases the
growth rate by 5-fold, an ultrasensitive response likely arising from competition
between two substrates for the active site of the inefficient bifunctional ProA*.
IMPORTANCE: The high-impact synonymous mutation we discovered in proB is
remarkable for two reasons. First, most polar effects documented in the
literature are detrimental. This finding demonstrates that polar effect mutations
can have strongly beneficial effects, especially when an organism is facing a
difficult environmental challenge for which it is poorly adapted. Furthermore,
the consequence of the synonymous mutation in proB is a 2-fold increase in the
level of ProA* but a disproportionately large 5.1-fold increase in growth rate.
While ultrasensitive responses are often found in signaling networks and genetic
circuits, an ultrasensitive response to an adaptive mutation has not been
previously reported.
PMID- 27501984
TI - AraC-Type Regulator Rbf Controls the Staphylococcus epidermidis Biofilm Phenotype
by Negatively Regulating the icaADBC Repressor SarR.
AB - : Regulation of icaADBC-encoded polysaccharide intercellular adhesin (PIA)/poly-N
acetylglucosasmine (PNAG) production in staphylococci plays an important role in
biofilm-associated medical-device-related infections. Here, we report that the
AraC-type transcriptional regulator Rbf activates icaADBC operon transcription
and PIA production in Staphylococcus epidermidis Purified recombinant Rbf did not
bind to the ica operon promoter region in electrophoretic mobility shift assays
(EMSAs), indicating that Rbf regulates ica transcription indirectly. To identify
the putative transcription factor(s) involved in Rbf-mediated icaADBC regulation,
the ability of recombinant Rbf to interact with the promoter sequences of known
icaADBC regulators was investigated. Recombinant Rbf bound to the sarR promoter
and not the sarX, sarA, sarZ, spx, and srrA promoters. Reverse transcription (RT)
PCR demonstrated that Rbf acts as a repressor of sarR transcription. PIA
expression and biofilm production were restored to wild-type levels in an rbf
sarR double mutant grown in brain heart infusion (BHI) medium supplemented with
NaCl, which is known to activate the ica locus, but not in BHI medium alone. RT
PCR further demonstrated that although Rbf does not bind the sarX promoter, it
nevertheless exerted a negative effect on sarX expression. Apparently, direct
downregulation of the SarR repressor by Rbf has a dominant effect over indirect
repression of the SarX activator by Rbf in the control of S. epidermidis PIA
production and biofilm formation. IMPORTANCE: The importance of Staphylococcus
epidermidis as an opportunistic pathogen in hospital patients with implanted
medical devices derives largely from its capacity to form biofilm. Expression of
the icaADBC-encoded extracellular polysaccharide is the predominant biofilm
mechanism in S. epidermidis clinical isolates and is tightly regulated. Here, we
report that the transcriptional regulator Rbf promotes icaADBC expression by
negatively regulating expression of sarR, which encodes an ica operon repressor.
Furthermore, Rbf indirectly represses the ica operon activator, SarX. The data
reveal complicated interplay between Rbf and two Sar family proteins in fine
tuning regulation of the biofilm phenotype and indicate that in the hierarchy of
biofilm regulators, IcaR is dominant over the Rbf-SarR-SarX axis.
PMID- 27501983
TI - Lipogenesis and Redox Balance in Nitrogen-Fixing Pea Bacteroids.
AB - Within legume root nodules, rhizobia differentiate into bacteroids that oxidize
host-derived dicarboxylic acids, which is assumed to occur via the tricarboxylic
acid (TCA) cycle to generate NAD(P)H for reduction of N2 Metabolic flux analysis
of laboratory-grown Rhizobium leguminosarum showed that the flux from
[(13)C]succinate was consistent with respiration of an obligate aerobe growing on
a TCA cycle intermediate as the sole carbon source. However, the instability of
fragile pea bacteroids prevented their steady-state labeling under N2-fixing
conditions. Therefore, comparative metabolomic profiling was used to compare free
living R. leguminosarum with pea bacteroids. While the TCA cycle was shown to be
essential for maximal rates of N2 fixation, levels of pyruvate (5.5-fold
reduced), acetyl coenzyme A (acetyl-CoA; 50-fold reduced), free coenzyme A (33
fold reduced), and citrate (4.5-fold reduced) were much lower in bacteroids.
Instead of completely oxidizing acetyl-CoA, pea bacteroids channel it into both
lipid and the lipid-like polymer poly-beta-hydroxybutyrate (PHB), the latter via
a type III PHB synthase that is active only in bacteroids. Lipogenesis may be a
fundamental requirement of the redox poise of electron donation to N2 in all
legume nodules. Direct reduction by NAD(P)H of the likely electron donors for
nitrogenase, such as ferredoxin, is inconsistent with their redox potentials.
Instead, bacteroids must balance the production of NAD(P)H from oxidation of
acetyl-CoA in the TCA cycle with its storage in PHB and lipids. IMPORTANCE:
Biological nitrogen fixation by symbiotic bacteria (rhizobia) in legume root
nodules is an energy-expensive process. Within legume root nodules, rhizobia
differentiate into bacteroids that oxidize host-derived dicarboxylic acids, which
is assumed to occur via the TCA cycle to generate NAD(P)H for reduction of N2
However, direct reduction of the likely electron donors for nitrogenase, such as
ferredoxin, is inconsistent with their redox potentials. Instead, bacteroids must
balance oxidation of plant-derived dicarboxylates in the TCA cycle with lipid
synthesis. Pea bacteroids channel acetyl-CoA into both lipid and the lipid-like
polymer poly-beta-hydroxybutyrate, the latter via a type II PHB synthase.
Lipogenesis is likely to be a fundamental requirement of the redox poise of
electron donation to N2 in all legume nodules.
PMID- 27501985
TI - Evidence that Oxidative Stress Induces spxA2 Transcription in Bacillus anthracis
Sterne through a Mechanism Requiring SpxA1 and Positive Autoregulation.
AB - : Bacillus anthracis possesses two paralogs of the transcriptional regulator,
Spx. SpxA1 and SpxA2 interact with RNA polymerase (RNAP) to activate the
transcription of genes implicated in the prevention and alleviation of oxidative
protein damage. The spxA2 gene is highly upregulated in infected macrophages, but
how this is achieved is unknown. Previous studies have shown that the spxA2 gene
was under negative control by the Rrf2 family repressor protein, SaiR, whose
activity is sensitive to oxidative stress. These studies also suggested that
spxA2 was under positive autoregulation. In the present study, we show by in vivo
and in vitro analyses that spxA2 is under direct autoregulation but is also
dependent on the SpxA1 paralogous protein. The deletion of either spxA1 or spxA2
reduced the diamide-inducible expression of an spxA2-lacZ construct. In vitro
transcription reactions using purified B. anthracis RNAP showed that SpxA1 and
SpxA2 protein stimulates transcription from a DNA fragment containing the spxA2
promoter. Ectopically positioned spxA2-lacZ fusion requires both SpxA1 and SpxA2
for expression, but the requirement for SpxA1 is partially overcome when saiR is
deleted. Electrophoretic mobility shift assays showed that SpxA1 and SpxA2
enhance the affinity of RNAP for spxA2 promoter DNA and that this activity is
sensitive to reductant. We hypothesize that the previously observed upregulation
of spxA2 in the oxidative environment of the macrophage is at least partly due to
SpxA1-mediated SaiR repressor inactivation and the positive autoregulation of
spxA2 transcription. IMPORTANCE: Regulators of transcription initiation are known
to govern the expression of genes required for virulence in pathogenic bacterial
species. Members of the Spx family of transcription factors function in control
of genes required for virulence and viability in low-GC Gram-positive bacteria.
In Bacillus anthracis, the spxA2 gene is highly induced in infected macrophages,
which suggests an important role in the control of virulence gene expression
during the anthrax disease state. We provide evidence that elevated
concentrations of oxidized, active SpxA2 result from an autoregulatory positive
feedback loop driving spxA2 transcription.
PMID- 27501987
TI - Developmental profile of select immune cells in mice infected with Trichinella
spiralis during the intestinal phase.
AB - Trichinella spiralis can cause immunosuppression during the intestinal phase of
early infection. However, changes in the peripheral blood during T. spiralis
early infection remain unclear. Here, select immune cells in mice infected with
500 muscle larvae (ML) of T. spiralis during the intestinal phase of infection
were studied. First, the recovery rates of the intestinal worms and female
fecundity were determined, and the results showed that the intestinal worms were
completely eliminated at 17 days post-infection (dpi) and that large numbers of
new-born larvae (NBL) were generated from 5 to 9dpi. Using flow cytometry, it was
shown that the number of CD4+ T cells and CD8+ T cells increased over the entire
intestinal phase, except on 7dpi when CD4+ T cells decreased significantly
compared to the control groups. Although both CD4+ and CD8+ T cells increased,
CD8+ T cells increased more than CD4+ T cells, leading to a lower CD4+/CD8+ ratio
compared to the control group. Subsequently, a depression of the proliferative
response of T cells to concanavalin A (Con A) was noticed at 7 and 11dpi.
Although the proliferative response of B cells to LPS was enhanced, the number of
B cells from mouse peripheral blood stimulated by T. spiralis antigens showed no
differences with the control group prior to 11dpi. The expression of CD14 on
monocyte-macrophages decreased during the same period, which meant that the
antigen-presenting response was reduced in the immune system of the infected
mice. Moreover, the alternatively activated macrophages were induced in T.
spiralis early infection. These data provide a better understanding of the
development of the intestinal immune response in mice infected with T. spiralis.
PMID- 27501986
TI - Stochastic anomaly of methylome but persistent SRY hypermethylation in disorder
of sex development in canine somatic cell nuclear transfer.
AB - Somatic cell nuclear transfer (SCNT) provides an excellent model for studying
epigenomic reprogramming during mammalian development. We mapped the whole genome
and whole methylome for potential anomalies of mutations or epimutations in SCNT
generated dogs with XY chromosomal sex but complete gonadal dysgenesis, which is
classified as 78, XY disorder of sex development (DSD). Whole genome sequencing
revealed no potential genomic variations that could explain the pathogenesis of
DSD. However, extensive but stochastic anomalies of genome-wide DNA methylation
were discovered in these SCNT DSD dogs. Persistent abnormal hypermethylation of
the SRY gene was observed together with its down-regulated mRNA and protein
expression. Failure of SRY expression due to hypermethylation was further
correlated with silencing of a serial of testis determining genes, including
SOX9, SF1, SOX8, AMH and DMRT1 in an early embryonic development stage at E34 in
the XY(DSD) gonad, and high activation of the female specific genes, including
FOXL2, RSPO1, CYP19A1, WNT4, ERalpha and ERbeta, after one postnatal year in the
ovotestis. Our results demonstrate that incomplete demethylation on the SRY gene
is the driving cause of XY(DSD) in these XY DSD dogs, indicating a central role
of epigenetic regulation in sex determination.
PMID- 27501988
TI - The roles of supernatant of macrophage treated by excretory-secretory products
from muscle larvae of Trichinella spiralis on the differentiation of C2C12
myoblasts.
AB - The excretory-secretory products (ESPs) released by the muscle-larvae (ML) stage
of Trichinella spiralis have been suggested to be involved in nurse cell
formation. However, the molecular mechanisms by which ML-ESPs modulate nurse cell
formation remain unclear. Macrophages exert either beneficial or deleterious
effects on tissue repair, depending on their activation/polarization state. They
are crucial for skeletal muscle repair, notably, via their actions on myogenic
precursor cells. However, these interactions during T. spiralis infection have
not been characterized. In the present study, the ability of conditioned medium
(CM) from J774A.1 macrophages treated with ML-ESPs to influence the
differentiation of murine myoblasts, and the mechanisms of this influence, were
investigated in vitro. The results showed that the expression of Myogenic
Regulatory Factors (MRFs) MyoD and myogenin, myosin heavy chain (MyHC), and the
p21 cyclin-dependent kinase inhibitor were reduced in CM treated cells compared
to their expression in the control group. These findings indicated that CM
inhibited myoblast differentiation. Conversely, CM promoted myoblast
proliferation and increased cyclin D1 levels. Taken together, results of our
study suggested that CM can indirectly influence myoblast differentiation and
proliferation, which provides a new method for the elucidation of the complex
mechanisms involved in cell-parasite and cell-cell interactions during T.
spiralis infection.
PMID- 27501989
TI - On the feasibility of the Chevron Notch Beam method to measure fracture toughness
of fine-grained zirconia ceramics.
AB - OBJECTIVE: The fracture toughness determination of fine-grained zirconia ceramics
using the chevron notched beam method (CNB) was investigated to assess the
feasibility of this method for quality assurance and material characterization.
METHODS: CNB tests were performed using four different yttria-stabilized zirconia
ceramics under various testing modes and conditions, including displacement
controlled and load-rate-controlled four point bending to assess the influence of
slow crack growth and identify most suitable test parameters. For comparison,
tests using single-edge V-notch beams (SEVNB) were conducted. RESULTS: It was
observed that the CNB method yields well-reproducible results. However, slow
crack growth effects significantly affect the measured KIC values, especially
when slow loading rates are used. To minimize the effect of slow crack growth,
the application of high loading rates is recommended. SIGNIFICANCE: Despite a
certain effort needed for setting up a sample preparation routine, the CNB method
is considered to be very useful for measuring and controlling the fracture
toughness of zirconia ceramics.
PMID- 27501990
TI - Hierarchical PEG-Based 3D Patterns Grafting from Polymer Substrate by Surface
Initiated Visible Light Photolithography.
AB - The precise construction of a hierarchical complex pattern on substrates is
required for numerous applications. Here, a strategy to fabricate well-defined
hierarchical three dimensional (3D) patterns on polymer substrate is developed.
This technique, which combines photolithography and visible light-induced surface
initiated living graft crosslinking polymerization (VSLGCP), can effectively
graft 3D patterns onto polymer substrate with high fidelity and controllable
height. Owing to the living nature of VSLGCP, hierarchical 3D patterns can be
prepared when a sequential living graft crosslinking process is performed on the
first formed patterns. As a proof-of-concept, a reactive two layer 3D pattern
with a morphology of lateral stripe on vertical stripe is prepared and employed
to separately immobilize model biomolecules, e.g., biotin and IgG. This two
component pattern can specifically interact with corresponding target proteins
successfully, indicating that this strategy has potential applications in the
fabrication of polymer-based multicomponent biomolecule microarrays.
PMID- 27501991
TI - Computer-assisted versus traditional freehand technique in fibular free flap
mandibular reconstruction: a morphological comparative study.
AB - The purpose of the study was to compare the accuracy of computer-assisted surgery
(CAS) and the traditional freehand technique for fibular free flap mandibular
reconstruction as well as to evaluate the accuracy of the CAS planning. The
medical records of 18 patients who underwent mandibular reconstruction with
fibular free flap were reviewed. The CAS group (n = 7) benefited from virtual
surgical planning and custom patient-specific plates and surgical cutting guides.
The Control group (n = 11) was treated by conventional surgery. Morphometric
comparison was done by calculating the differences in specific linear and angular
parameters on pre- and postoperative CT-scans for both groups by using ProPlan
CMF(r) software. Symmetry was also assessed by calculating the ratio of the
affected versus the nonaffected side. In the CAS group, planned and postoperative
CT-scans were compared to evaluate accuracy. The morphometric comparison showed
no statistically significant differences between the groups except for the axial
angle on the nonaffected side (mean difference 1.0 degrees in the CAS group
versus 2.9 degrees in the Control group; p = 0.03). Ratios of the affected side
over the nonaffected side showed no differences between the two groups. In the
CAS group, the accuracy assessment showed a mean distance deviation of 2.3 mm for
mandibular osteotomies and 1.9 mm for fibular osteotomies. Our results indicated
that CAS and the conventional freehand techniques were comparable in their
ability to provide a satisfactory morphological fibular free flap mandibular
reconstruction. Moreover, the accuracy of the CAS technique was within the range
reported in the literature.
PMID- 27501992
TI - Erratum to: Comparison of acyclovir and famciclovir for the treatment of Bell's
palsy.
PMID- 27501993
TI - Bowl-shaped Troger's bases and their recognition properties.
AB - The tris-Troger's bases (TBs) are electron-rich fluorescent concave receptors due
to the incorporation of naphthalene or triphenylene moieties (calix-1 and calix
2). The structures of the TBs were studied using SXRD to reveal the propensity to
bind nitroaromatics. Titration with explosive-related nitro-compounds suggests
that the TBs may be used for sensing explosives.
PMID- 27501994
TI - Maximizing the benefits and minimizing the risks of intervention programs to
address micronutrient malnutrition: symposium report.
AB - Interventions to address micronutrient deficiencies have large potential to
reduce the related disease and economic burden. However, the potential risks of
excessive micronutrient intakes are often not well determined. During the Global
Summit on Food Fortification, 9-11 September 2015, in Arusha, a symposium was
organized on micronutrient risk-benefit assessments. Using case studies on folic
acid, iodine and vitamin A, the presenters discussed how to maximize the benefits
and minimize the risks of intervention programs to address micronutrient
malnutrition. Pre-implementation assessment of dietary intake, and/or biomarkers
of micronutrient exposure, status and morbidity/mortality is critical in
identifying the population segments at risk of inadequate and excessive intake.
Dietary intake models allow to predict the effect of micronutrient interventions
and their combinations, e.g. fortified food and supplements, on the proportion of
the population with intakes below adequate and above safe thresholds. Continuous
monitoring of micronutrient intake and biomarkers is critical to identify whether
the target population is actually reached, whether subgroups receive excessive
amounts, and inform program adjustments. However, the relation between regular
high intake and adverse health consequences is neither well understood for many
micronutrients, nor do biomarkers exist that can detect them. More accurate and
reliable biomarkers predictive of micronutrient exposure, status and function are
needed to ensure effective and safe intake ranges for vulnerable population
groups such as young children and pregnant women. Modelling tools that integrate
information on program coverage, dietary intake distribution and biomarkers will
further enable program makers to design effective, efficient and safe programs.
PMID- 27501996
TI - Reduced Intramolecular Twisting Improves the Performance of 3D Molecular
Acceptors in Non-Fullerene Organic Solar Cells.
AB - A small-molecular acceptor, tetraphenylpyrazine-perylenediimide tetramer (TPPz
PDI4 ), which has a reduced extent of intramolecular twisting compared to two
other small-molecular acceptors is designed. Benefiting from the lowest extent of
intramolecular twisting, TPPz-PDI4 exhibits the highest aggregation tendency and
electron mobility, and therefore achieves a highest power conversion efficiency
of 7.1%.
PMID- 27501997
TI - p-Hydroxylcinnamaldehyde induces the differentiation of oesophageal carcinoma
cells via the cAMP-RhoA-MAPK signalling pathway.
AB - p-Hydroxylcinnamaldehyde (CMSP) has been identified as an inhibitor of the growth
of various cancer cells. However, its function in oesophageal squamous cell
carcinoma (ESCC) and the underlying mechanism remain unclear. The aim of the
present study was to characterize the differentiation effects of CMSP, as well as
its mechanism in the differentiation of ESCC Kyse30 and TE-13 cells. The function
of CMSP in the viability, colony formation, migration and invasion of Kyse30 and
TE-13 cells was determined by MTS, colony-formation, wound healing and transwell
assays. Western blotting and pull-down assays were used to investigate the effect
of CMSP on the expression level of malignant markers of ESCC, as well as the
activity of MAPKs, RhoA and GTP-RhoA in Kyse30 and TE-13 cells. We found that
CMSP could inhibit proliferation and migration and induce Kyse30 and TE-13 cell
differentiation, characterized by dendrite-like outgrowth, decreased expression
of tumour-associated antigens, as well as the decreased expression of malignant
markers. Furthermore, increased cAMP, p-P38 and decreased activities of ERK, JNK
and GTP-RhoA, were detected after treatment with CMSP. These results indicated
that CMSP induced the differentiation of Kyse30 and TE-13 cells through mediating
the cAMP-RhoA-MAPK axis, which might provide new potential strategies for ESCC
treatment.
PMID- 27501998
TI - Treatment of heparin-induced thrombocytopenia before and after the implementation
of a hemostatic and antithrombotic stewardship program.
AB - In October 2013, we implemented a hemostatic and antithrombotic (HAT) stewardship
program with the primary focus of ensuring appropriate use of intravenous direct
thrombin inhibitors (DTI) in patients with heparin-induced thrombocytopenia
(HIT). We sought to compare the duration and cost of DTI therapy for the
management of HIT before and after implementation of the HAT stewardship program.
Following institutional review board approval, we conducted a single center,
retrospective chart review of all patients with a suspected diagnosis of HIT as
assessed by an anti-heparin-PF4 enzyme-linked immunosorbent assay 6 months pre
HAT and post-HAT implementation. Patients were excluded if they were initiated on
a DTI at an outside hospital, had a prior episode of HIT, or received mechanical
circulatory support. Clinical characteristics, including demographics,
comorbidities, medications, laboratory values, clinical and safety outcomes,
length of stay, and mortality, were collected. A total of 592 patients were
included; 333 patients were evaluated pre-HAT, while 259 patients were evaluated
post-HAT. The mean duration of DTI treatment was significantly decreased in the
post-HAT cohort (6.64 vs 5.17 days, p = 0.01), primarily driven by decreased
duration of use for patients with suspected HIT (4.07 vs 2.86 days, p = 0.01).
The HAT Stewardship program demonstrated a total decrease in annual costs
associated with the diagnosis and management of HIT of $248,500. Our results
indicate that the implementation of the HAT stewardship program had a significant
impact on reducing the duration and costs of DTI therapy and the costs of
laboratory evaluations in the management of HIT at our institution.
PMID- 27501999
TI - Additive prognostic value of left ventricular ejection fraction to the TIMI risk
score for in-hospital and long-term mortality in patients with ST segment
elevation myocardial infarction.
AB - To investigate whether the addition of left ventricular ejection fraction (LVEF)
to the TIMI risk score enhances the prediction of in-hospital and long-term death
in ST segment elevation myocardial infarction (STEMI) patients. 673 patients with
STEMI were divided into three groups based on TIMI risk score for STEMI: low-risk
group (TIMI <=3, n = 213), moderate-risk group (TIMI 4-6, n = 285), and high-risk
group (TIMI >=7, n = 175). The predictive value was evaluated using the receiver
operating characteristic. Multivariate logistic regression was used to determine
risk predictors. The rates of in-hospital death (0.5 vs 3.2 vs 10.3 %, p < 0.001)
and major adverse cardiovascular events (14.6 vs 22.5 vs 40.6 %, p < 0.001) were
significantly higher in high-risk group. Multivariate analysis showed that TIMI
risk score (OR 1.24, 95 % CI 1.04-1.48, P = 0.015) and LVEF (OR 3.85, 95 % CI
1.58-10.43, P = 0.004) were independent predictors of in-hospital death. LVEF had
good predictive value for in-hospital death (AUC: 0.838 vs 0.803, p = 0.571) or 1
year death (AUC: 0.743 vs 0.728, p = 0.775), which was similar to TIMI risk
score. When compared with the TIMI risk score alone, the addition of LVEF was
associated with significant improvements in predicting in-hospital (AUC: 0.854 vs
0.803, p = 0.033) or 1-year death (AUC: 0.763 vs 0.728, p = 0.016). The addition
of LVEF to TIMI risk score enhanced net reclassification improvement (0.864 for
in-hospital death, p < 0.001; 0.510 for 1-year death, p < 0.001). LVEF was
associated with in-hospital and long-term mortality in STEMI patients and had
additive prognostic value to TIMI risk score.
PMID- 27502000
TI - A new approach to regression analysis of censored competing-risks data.
AB - An approximate likelihood approach is developed for regression analysis of
censored competing-risks data. This approach models directly the cumulative
incidence function, instead of the cause-specific hazard function, in terms of
explanatory covariates under a proportional subdistribution hazards assumption.
It uses a self-consistent iterative procedure to maximize an approximate
semiparametric likelihood function, leading to an asymptotically normal and
efficient estimator of the vector of regression parameters. Simulation studies
demonstrate its advantages over previous methods.
PMID- 27502001
TI - Natriuretic peptide levels taken following unplanned admission to a cardiology
department predict the duration of hospitalization.
AB - AIMS: Natriuretic peptide (NP) levels are routinely employed as useful diagnostic
and prognostic tools in the evaluation of patients with heart failure (HF). As
hospitalization is the major consumer of healthcare resources, the prognostic
power of admission NPs with regard to the duration of hospitalization deserves
further investigation. METHODS AND RESULTS: We assessed retrospectively the
association between NP values sampled shortly following unplanned admission and
the duration of hospitalization in 2978 patients admitted to a cardiology
department. Duration of hospitalization (hours) and survival were determined by
interrogation of the electronic medical records system. Associations with peptide
levels were estimated using regression models and receiver operating
characteristic (ROC) analysis. The results demonstrate a significant positive
relationship between NP levels and the duration of hospitalization, after
adjusting for age (P < 0.001). The median duration of hospitalization for the
lowest BNP and NT-proBNP quintiles were 80 and 97 h, respectively, vs. 224.5 and
236 h for the highest quintiles. Using cut-off levels of 115 pmol/L for BNP and
390 pmol/L for NT-proBNP, the peptides have a positive predictive value of 78%
and 85% for a stay >4 days. During follow-up, NP levels were strongly predictive
of all-cause mortality. CONCLUSION: The results quantify the strong relationship
between NP levels taken following an unplanned admission to a cardiology
department and the duration of hospitalization. This information permits improved
identification of a patient population likely to require a prolonged hospital
stay and consume more healthcare resources. Such patients may require a more
aggressive diagnostic, treatment, and management strategy.
PMID- 27502002
TI - [Lung carcinoma screening].
PMID- 27502003
TI - [Prerequisites for a successful lung cancer screening program].
AB - The American national lung cancer screening trial (NLST) has provided the first
confirmation of a reduction in lung cancer mortality by using low-dose multislice
computed tomography (MSCT). Preliminary evaluations of smaller European trials
could not confirm such a reduction. The final evaluation of the larger Dutch
Belgian NELSON trial and five other European trials are expected within the next
1-2 years. The results of the completed rounds of screening in all these studies
indicate that the margin between a positive and a negative benefit-to-harm
balance will be narrow. In such a scenario it will be crucial to optimize the
definition of the target population for screening as a high-risk group for lung
cancer, the quality of screening in terms of high sensitivity and specificity as
well as high quality treatment and an effective ongoing control of program
quality. Not all healthcare systems are suitable to fulfill these prerequisites.
PMID- 27502005
TI - [(18)F-FDG PET/CT: Image-guided surveillance in advanced head and neck cancer as
an alternative to neck dissection].
PMID- 27502004
TI - [Early recognition of lung cancer in workers occupationally exposed to asbestos].
AB - Despite the fact that working with asbestos and placing it on the market have
been banned in Germany since 1993 according to the Ordinance on Hazardous
Substances, asbestos-related diseases of the lungs and pleura are still the
leading cause of death in occupational diseases. The maximum industrial usage of
asbestos was reached in former West Germany in the late 1970s and in former East
Germany the late 1980s. Occupational diseases, mainly mesotheliomas and lung
cancer emerging now are thus caused by asbestos exposure which occurred 30-40
years earlier. It is known that the combination of smoking and asbestos exposure
results in a superadditive increase in the risk to develop lung cancer. No
suitable screening methods for early detection of malignant mesothelioma are
currently available and the therapeutic options are still very limited; however,
the national lung screening trial (NLST) has shown for the first time that by
employing low-dose computed tomography (LDCT) in heavy smokers, lung cancer
mortality can be significantly reduced. According to current knowledge the
resulting survival benefits far outweigh the potential risks involved in the
diagnostic work-up of suspicious lesions. These results in association with the
recommendations of international medical societies and organizations were pivotal
as the German statutory accident insurance (DGUV) decided to provide LDCT as a
special occupational medical examination for workers previously exposed to
asbestos and with a particularly high risk for developing lung cancer.
PMID- 27502006
TI - Modeling the mechanics of axonal fiber tracts using the embedded finite element
method.
AB - A subject-specific human head finite element model with embedded axonal fiber
tractography obtained from diffusion tensor imaging was developed. The axonal
fiber tractography finite element model was coupled with the volumetric elements
in the head model using the embedded element method. This technique enables the
calculation of axonal strains and real-time tracking of the mechanical response
of the axonal fiber tracts. The coupled model was then verified using pressure
and relative displacement-based (between skull and brain) experimental studies
and was employed to analyze a head impact, demonstrating the applicability of
this method in studying axonal injury. Following this, a comparison study of
different injury criteria was performed. This model was used to determine the
influence of impact direction on the extent of the axonal injury. The results
suggested that the lateral impact loading is more dangerous compared to loading
in the sagittal plane, a finding in agreement with previous studies. Through this
analysis, we demonstrated the viability of the embedded element method as an
alternative numerical approach for studying axonal injury in patient-specific
human head models.
PMID- 27502008
TI - Scientific Abstracts of the 13th Congress of the European Academy of Paediatric
Dentistry (EAPD).
PMID- 27502007
TI - Down-regulation of Irf8 by Lyz2-cre/loxP accelerates osteoclast differentiation
in vitro.
AB - Interferon regulatory factor 8 (Irf8) is a transcription factor that negatively
regulates osteoclast differentiation and Irf8 global knockout (Irf8 -/-) mice
have been shown to have reduced bone volume resulting from increased osteoclast
numbers. However, detailed analysis of the functions of Irf8 in osteoclast
precursors with a monocyte/macrophage linage is difficult, because the population
and properties of hematopoietic cells in Irf8 -/- mice are severely altered.
Therefore, to clearly elucidate the functions of Irf8 during osteoclastogenesis,
we established myeloid cell-specific Irf8 conditional knockout (Irf8 fl/fl ;Lyz2
cre/+) mice. We found that trabecular bone volume in the Irf8 fl/fl ;Lyz2 cre/+
mice was not significantly affected, while exposure to M-CSF and RANKL
significantly increased TRAP activity in vitro in osteoclasts that underwent
osteoclastogenesis from bone marrow-derived macrophages (BMMs) induced from bone
marrow cells (BMCs) of those mice by addition of M-CSF. Our results also showed
that expression of Irf8 mRNA and protein in BMMs obtained from Irf8 fl/fl ;Lyz2
cre/+ mice and cultured with M-CSF was reduced. These findings predicted that
Lyz2/Lyz2-cre expression is induced when BMCs differentiate into BMMs in cultures
with M-CSF. In osteoclast differentiation cultures, Lyz2 was gradually increased
by M-CSF during the first 3 days of culture, then rapidly decreased by the
addition of RANKL with M-CSF during the next 3 days. Furthermore, BMCs
differentiated into osteoclasts while maintaining a low level of Lyz2 expression
when cultured simultaneously with both M-CSF and RANKL from the initiation of
culture. These findings suggest that Lyz2-cre expression is induced along with
differentiation to BMMs by BMCs obtained from Irf8 fl/fl ;Lyz2 cre/+ mice and
cultured with M-CSF. In addition, Irf8 was down-regulated by activation of the
cre/loxP recombination system in BMMs and osteoclastogenesis was accelerated.
Based on our results, we propose the existence in vivo of a new lineage of
osteoclast precursors among BMCs, which differentiate into osteoclasts without up
regulation of Lyz2 expression.
PMID- 27502009
TI - Hemorrhage is the most common cause of neonatal mortality in patients with
sacrococcygeal teratoma.
AB - BACKGROUND: A small percentage of neonates with sacrococcygeal teratoma die
shortly after birth from hemorrhagic complications. The incidence of and risk
factors associated with hemorrhagic mortality are unknown. In this multicenter
study we determined the incidence of early death in neonates born with SCT and
evaluated potential risk factors for hemorrhagic mortality. METHODS: 235 children
with SCT treated from 1970 to 2010 in the Netherlands were retrospectively
included. The following candidate risk factors for hemorrhagic mortality were
examined: sex, prematurity, Altman type, tumor volume, tumor histology, necessity
of emergency operation and time of diagnosis. RESULTS: Eighteen patients (7.7%)
died at a median age of 163.5days (range 1.7-973days). Nine patients died of a
malignancy. Nine others (3.8%) died postnatally (age 1-27days), six even within
two days after birth. In seven of these nine patients death was related to tumor
hemorrhage and/or circulatory failure. Risk factors for hemorrhagic mortality
were prematurity, tumor volume>1000cm3 and performance of an emergency operation.
CONCLUSIONS: Hemorrhagic mortality of neonates with SCT is relatively high (3.8%)
representing almost 70% of the overall mortality in the neonatal period. High
output cardiac failure, internal tumor hemorrhage and perioperative bleeding were
the most common causes of early death and were all strongly associated with
larger tumor sizes. LEVEL-OF-EVIDENCE RATING: II (Retrospective study).
PMID- 27502010
TI - Multiple orifices and cholangiography with a "fire-like" appearance after Kasai
hepatoportoenterostomy for biliary atresia.
AB - A 21-year-old female underwent a Kasai hepatoportoenterostomy with Roux-en-Y
reconstruction for typeIII biliary atresia at age 63 days. At the age of 19
years, she developed cholangitis and CT scan revealed hepatolithiasis. She
presented for treatment of the intrahepatic stone and the hepatportoenterostomy
was directly visualized with double-balloon endoscopy (DBE). Endoscopic findings
showed multiple intrahepatic bile ducts open to the jejunum through multiple
orifices. Cholangiography showed narrowing of intrahepatic bile duct branches
with a "fire-like" appearance. These findings have not been previously reported,
since endoscopic approaches to patients with a hepaticojejunostomy were limited.
DBE was useful to directly visualize the anastomosis in a patient status-post the
Kasai operation for biliary atresia with a Rouxen-Y reconstruction.
PMID- 27502011
TI - Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus):
establishment of optimal dosage and administration in medicated feed.
AB - The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was
studied after single intravenous (10 mg kg-1 ) and oral (100 mg kg-1 )
administration. The plasma concentration-time data of florfenicol were described
by an open one-compartment model. The elimination half-life (t1/2 ) was estimated
to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h-1
. The apparent volume distribution (Vd ) was calculated to be 0.86 L kg-1 and the
mean residence time (MRTiv ) was 30.2 h. Following oral administration, the
maximum plasma concentration (Cmax ) of 55.4 MUg mL-1 was reached at 12 h (Tmax
). The absorption constant (ka ) was 0.158 h-1 . The bioavailability was
estimated to be 57.1%. The low bioavailability observed at higher doses was
explained by the saturation of the mechanisms of absorption. The drug absorption
process was limited by its inherent low solubility, which limited the amount of
available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic
data, an optimal dosing schedule for FF administration is hereby provided. Based
on the minimum inhibitory concentration found for susceptible strains of
Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg
FF kg-1 , followed by 6 maintenance doses at 18 mg kg-1 /daily could be effective
against furunculosis in turbot.
PMID- 27502012
TI - Adaptation and memory in innate immunity.
PMID- 27502013
TI - Promotion of formyl peptide receptor 1-mediated neutrophil chemotactic migration
by antimicrobial peptides isolated from the centipede Scolopendra subspinipes
mutilans.
AB - We investigated the effects of two antimicrobial peptides (AMPs) isolated from
Scolopendra subspinipes mutilans on neutrophil activity. Stimulation of mouse
neutrophils with the two AMPs elicited chemotactic migration of the cells in a
pertussis toxin-sensitive manner. The two AMPs also stimulated activation of ERK
and Akt, which contribute to chemotactic migration of neutrophils. We found that
AMP-stimulated neutrophil chemotaxis was blocked by a formyl peptide receptor
(FPR) 1 antagonist (cyclosporin H); moreover the two AMPs stimulated the
chemotactic migration of FPR1-expressing RBL-2H3 cells but not of vector
expressing RBL-2H3 cells. We also found that the two AMPs stimulate neutrophil
migration in vivo, and that this effect is blocked in FPR1-deficient mice. Taken
together, our results suggest that the two AMPs stimulate neutrophils, leading to
chemotactic migration through FPR1, and the two AMPs will be useful for the study
of FPR1 signaling and neutrophil activation. [BMB Reports 2016; 49(9): 520-525].
PMID- 27502014
TI - The cellular basis of dendrite pathology in neurodegenerative diseases.
AB - One of the characteristics of the neurons that distinguishes them from other
cells is their complex and polarized structure consisting of dendrites, cell
body, and axon. The complexity and diversity of dendrites are particularly well
recognized, and accumulating evidences suggest that the alterations in the
dendrite structure are associated with many neurodegenerative diseases. Given the
importance of the proper dendritic structures for neuronal functions, the
dendrite pathology appears to have crucial contribution to the pathogenesis of
neurodegenerative diseases. Nonetheless, the cellular and molecular basis of
dendritic changes in the neurodegenerative diseases remains largely elusive.
Previous studies in normal condition have revealed that several cellular
components, such as local cytoskeletal structures and organelles located locally
in dendrites, play crucial roles in dendrite growth. By reviewing what has been
unveiled to date regarding dendrite growth in terms of these local cellular
components, we aim to provide an insight to categorize the potential cellular
basis that can be applied to the dendrite pathology manifested in many
neurodegenerative diseases. [BMB Reports 2017; 50(1): 5-11].
PMID- 27502015
TI - Databases and tools for constructing signal transduction networks in cancer.
AB - Traditionally, biologists have devoted their careers to studying individual
biological entities of their own interest, partly due to lack of available data
regarding that entity. Large, highthroughput data, too complex for conventional
processing methods (i.e., "big data"), has accumulated in cancer biology, which
is freely available in public data repositories. Such challenges urge biologists
to inspect their biological entities of interest using novel approaches, firstly
including repository data retrieval. Essentially, these revolutionary changes
demand new interpretations of huge datasets at a systems-level, by so called
"systems biology". One of the representative applications of systems biology is
to generate a biological network from high-throughput big data, providing a
global map of molecular events associated with specific phenotype changes. In
this review, we introduce the repositories of cancer big data and cutting-edge
systems biology tools for network generation, and improved identification of
therapeutic targets. [BMB Reports 2017; 50(1): 12-19].
PMID- 27502016
TI - Meis: New friends of Pax.
AB - The generation of neuronal diversity in the mammalian brain is a multistep
process, beginning with the regional patterning of neural stem- and progenitor
cell domains, the commitment of these cells toward a general neuronal fate,
followed by the selection of a particular neuronal subtype and the
differentiation of postmitotic neurons. Each of these steps as well as the
transitions between them require precisely controlled changes in transcriptional
programs. Although a large number of transcription factors are known to regulate
neurogenesis in the embryonic and adult central nervous system, the sheer number
of neuronal cell types in the brain and the complexity of the cellular processes
that accompany their production suggest that transcription factors act
cooperatively to control individual steps in neurogenesis. In fact, combinatorial
regulation by sets of transcription factors has emerged as a versatile mode to
control cell fate specification. Here, I discuss our recent finding that members
of the MEIS-subfamily of TALE-transcription factors, originally identified as HOX
cofactors in non-neural tissues, function in concert with PAX-proteins in the
regulation of cell fate specification and neuronal differentiation in the
embryonic and adult brain.
PMID- 27502017
TI - Force sensitivity of multilayer graphene optomechanical devices.
AB - Mechanical resonators based on low-dimensional materials are promising for force
and mass sensing experiments. The force sensitivity in these ultra-light
resonators is often limited by the imprecision in the measurement of the
vibrations, the fluctuations of the mechanical resonant frequency and the heating
induced by the measurement. Here, we strongly couple multilayer graphene
resonators to superconducting cavities in order to achieve a displacement
sensitivity of 1.3 fm Hz(-1/2). This coupling also allows us to damp the
resonator to an average phonon occupation of 7.2. Our best force sensitivity, 390
zN Hz(-1/2) with a bandwidth of 200 Hz, is achieved by balancing measurement
imprecision, optomechanical damping, and measurement-induced heating. Our results
hold promise for studying the quantum capacitance of graphene, its magnetization,
and the electron and nuclear spins of molecules adsorbed on its surface.
PMID- 27502018
TI - Ginsenoside Rg3, a Gating Modifier of EAG Family K+ Channels.
AB - Ginsenoside 20(S)-Rg3 (Rg3) is a steroid glycoside that induces human ether-a-go
go-related gene type 1 (hERG1, Kv11.1) channels to activate at more negative
potentials and to deactivate more slowly than normal. However, it is unknown
whether this action is unique to hERG1 channels. Here we compare and contrast the
mechanisms of actions of Rg3 on hERG1 with three other members of the ether-a-go
go (EAG) K(+) channel gene family, including EAG1 (Kv10.1), ERG3 (Kv11.3), and
ELK1 (Kv12.1). All four channel types were heterologously expressed in Xenopus
laevis oocytes, and K(+) currents were measured using the two-microelectrode
voltage-clamp technique. At a maximally effective concentration, Rg3 shifted the
half-point of voltage-dependent activation of currents by -14 mV for ERG1 (EC50 =
414 nM), -20 mV for ERG3 (EC50 = 374 nM), -28 mV for EAG1 (EC50 = 1.18 MUM), and
more than -100 mV for ELK1 (EC50 = 197 nM) channels. Rg3 also induced slowing of
ERG1, ERG3, and ELK1 channel deactivation and accelerated the rate of EAG1
channel activation. A Markov model was developed to simulate gating and the
effects of Rg3 on the voltage dependence of activation of hELK1 channels.
Understanding the mechanism underlying the action of Rg3 may facilitate the
development of more potent and selective EAG family channel activators as
therapies for cardiovascular and neural disorders.
PMID- 27502019
TI - Electrolyte Cations Binding with Extracellular Polymeric Substances Enhanced
Microcystis Aggregation: Implication for Microcystis Bloom Formation in Eutrophic
Freshwater Lakes.
AB - The hydrodynamic and structural properties of Microcystis extracellular polymeric
substances (EPS) in electrolytes with different valences and ionic strengths were
investigated via using dynamic light scattering, the fluorescence excitation
emission matrix coupled with parallel factor (EEM-PARAFAC) analysis, two
dimensional correlation spectroscopy (2D-COS), and cryogenic transmission
electron microscopy (Cryo-TEM). The hydrodynamic diameters of EPS colloids
exhibited no variation for monovalent NaCl but a substantial increase for
divalent CaCl2 and MgCl2. However, the negative electrophoretic mobilities for
all complexes indicated that charge neutralization would not be the main
mechanism for EPS aggregation. Application of EEM-PARAFAC and 2D-Fourier
transform infrared (FTIR)-COS revealed obvious electrolyte binding potential with
both fluorescent phenolic and aromatic compounds and nonfluorescent
polysaccharides. The complexation model showed that divalent Ca(2+) and Mg(2+)
exhibited a strong binding capability with phenolic -OH, aromatic C?C, and
polysaccharide C-O groups, while the monovalent electrolyte exhibited negligible
association with these groups. Such a strong complexation can bridge each
individual biomolecule together to form EPS aggregates and Microcystis colonies,
as supported by in situ Cryo-TEM and light microscope observation, respectively.
Given the increased concentration in natural ecosystems, electrolyte cations,
especially divalent cations, would play increased roles in Microcystis bloom
formation and thus should be considered.
PMID- 27502020
TI - Alveolar bone grafting with simultaneous cleft lip rhinoplasty.
AB - BACKGROUND: Optimal timing for cleft lip rhinoplasty is controversial. Definitive
rhinoplasty is deferred until facial skeletal growth is completed. Intermediate
rhinoplasty is performed after stabilization of the grafted alveolar bone,
because the grafted bone tends to be absorbed over several months
postoperatively, distorting the nasal profile. Here, we report our experience
with simultaneous rhinoplasty during alveolar bone grafting for indicated
patients, describe our surgical technique that ensures long-term bone graft
survival, and report graft take rates and nasal profile changes. METHODS: This
retrospective chart review included a total of 54 patients; 44 underwent alveolar
bone grafting only, and 10 underwent simultaneous cleft lip rhinoplasty. All
surgeries were conducted with a judicious mucosal incision for tensionless wound
closure. Bone graft take was evaluated with dental radiographs by the Bergland
classification. Further, nasal aesthetic outcome was evaluated with medical
photographs, based on nostril height and width and alar base width. RESULTS: In
total, 96.3% of clefts showed graft success with Type I (66.7%) or Type II
(27.8%) classifications; only 3.7% of clefts showed unfavorable results
classified as Type III, and no clefts showed Type IV failure. The nasal shape was
flatter with a decreased nostril height and increased nostril width after
alveolar bone grafting, while nostril height was increased and nostril width was
decreased in patients who underwent simultaneous rhinoplasty. CONCLUSION: With
surgical techniques ensuring alveolar bone graft survival, simultaneous cleft lip
rhinoplasty can result in nasal aesthetic improvement for patients with severe
nasal deformities, decreasing the number of operations.
PMID- 27502021
TI - Abstracts from National Young Researchers' Forum on Materials Science and
Technology, XIII AIMAT National Congress, National Biomaterial Congress - SIB,
July 2016, Ischia, Italy.
PMID- 27502022
TI - SCCmec-associated psm-mec mRNA promotes Staphylococcus epidermidis biofilm
formation.
AB - Biofilm formation is considered the major pathogenic mechanism of Staphylococcus
epidermidis-associated nosocomial infections. Reports have shown that SCCmec
associated psm-mec regulated methicillin-resistant Staphylococcus aureus
virulence and biofilm formation. However, the role of psm-mec in S. epidermidis
remains unclear. To this purpose, we analysed 165 clinical isolates of S.
epidermidis to study the distribution, mutation and expression of psm-mec and the
relationship between this gene and biofilm formation. Next, we constructed three
psm-mec deletion mutants, one psm-mec transgene expression strain (p221) and two
psm-mec point mutant strains (pM, pAG) to explore its effects on S. epidermidis
biofilm formation. Then, the amount of biofilm formation, extracellular DNA
(eDNA) and Triton X-100-induced autolysis of the constructed strains was
measured. Results of psm-mec deletion and transgene expression showed that the
gene regulated S. epidermidis biofilm formation. Compared with the control
strains, the ability to form biofilm, Triton X-100-induced autolysis and the
amount of eDNA increased in the p221 strain and the two psm-mec mutants pM and
pAG expressed psm-mec mRNA without its protein, whereas no differences were
observed among the three constructed strains, illustrating that psm-mec mRNA
promoted S. epidermidis biofilm formation through up-regulation of bacterial
autolysis and the release of eDNA. Our results reveal that acquisition of psm-mec
promotes S. epidermidis biofilm formation.
PMID- 27502023
TI - Citricoccus lacusdiani sp. nov., an actinobacterium promoting Microcystis growth
with limited soluble phosphorus.
AB - A novel actinobacterium, designated strain JXJ CY 21T, was isolated from the
culture mass of Microcystis sp. FACHB-905 collected from Lake Dianchi, South-west
China. Polyphasic taxonomic study revealed that the isolate should be a member of
the genus Citricoccus. Comparison of the 16S rRNA gene sequence of strain JXJ CY
21T with the available sequences in the GenBank database showed that the strain
is closely related to Citricoccus zhacaiensis FS24T (97.8 % similarity),
Citricoccus parietis 02-Je-010T (97.7 %), Citricoccus terreus V3M1T (97.6 %),
Citricoccus nitrophenolicus PNP1T (97.2 %), Citricoccus alkalitolerans YIM 70010T
(97.2 %) and Citricoccus muralis 4-0T (97.0 %). The DNA-DNA hybridization values
between strain JXJ CY 21T and the related type strains C. zhacaiensis FS24T and
C. parietis 02-Je-010T were 16.0 +/- 2.6 and 5.4 +/- 1.7 %, respectively. The
peptidoglycan in the cell wall was A4alpha type containing lysine-glutamic acid
glycine. The major respiratory menaquinone was found to be MK-8 (H2) (98.5 %),
while the major cellular fatty acids (>10 %) were anteiso-C15:0, iso-C16:0, iso
C15:0 and iso-C14:0. The polar lipids detected were diphosphatidylglycerol,
phosphatidylinositol, phosphatidylglycerol, an unidentified phospholipid and an
unidentified glycolipid. The DNA G + C content was determined to be 62.7 mol%.
Strain JXJ CY 21T can solubilize both insoluble inorganic and organic phosphates
up to 24.7 and 1.7 mg/l respectively. This property of the novel actinobacterium
acts as a modulator for enhancement of growth of Microcystis sp. FACHB-905 in the
lake ecosystem where the amount of soluble phosphate is limited. On the basis of
the above taxonomic data, strain JXJ CY 21T represents a novel species of the
genus Citricoccus, for which the name Citricoccus lacusdiani sp. nov. is
proposed. The type strain is JXJ CY 21T (=KCTC 29653T = DSM 29160T).
PMID- 27502024
TI - Occlusive bandaging of wounds with decreased circulation promotes growth of
anaerobic bacteria and necrosis: case report.
AB - BACKGROUND: Topical occlusive/semi-occlusive dressings that induce a damp and
trapped environment are widely used in wound treatment. Subjecting the wound with
impaired circulation to such trapped/air-free environment potentiates the growth
of anaerobic bacteria and risk for serious infection. CASE PRESENTATION: We
present a case of previously healthy Swedish male that had a muscle contusion
after heavy trauma that induced impaired circulation. The application of an
occlusive bandage to the post-traumatic wound on the patient resulted in a poly
microbial anaerobic infection and necrosis. These complications were treated
successfully with antibiotics and open dressing of the wound. CONCLUSION: The
pathophysiology of difficult- to- treat ulcers should be reviewed by the
physician and occlusive dressing should be avoided when treating wounds with
impaired circulation.
PMID- 27502026
TI - Modeling size controlled nanoparticle precipitation with the co-solvency method
by spinodal decomposition.
AB - The co-solvency method is a method for the size controlled preparation of
nanoparticles like polymersomes, where a poor co-solvent is mixed into a
homogeneous copolymer solution to trigger precipitation of the polymer. The size
of the resulting particles is determined by the rate of co-solvent addition. We
use the Cahn-Hilliard equation with a Flory-Huggins free energy model to describe
the precipitation of a polymer under changing solvent quality by applying a time
dependent Flory-Huggins interaction parameter. The analysis focuses on the
characteristic size R of polymer aggregates that form during the initial spinodal
decomposition stage, and especially on how R depends on the rate s of solvent
quality change. Both numerical results and a perturbation analysis predict a
power law dependence R~s(-1/6), which is in agreement with power laws for the
final particle sizes that have been reported from experiments and molecular
dynamics simulations. Hence, our model results suggest that the nanoparticle size
in size-controlled precipitation is essentially determined during the spinodal
decomposition stage.
PMID- 27502025
TI - TALEN-based generation of a cynomolgus monkey disease model for human
microcephaly.
AB - Gene editing in non-human primates may lead to valuable models for exploring the
etiologies and therapeutic strategies of genetically based neurological disorders
in humans. However, a monkey model of neurological disorders that closely mimics
pathological and behavioral deficits in humans has not yet been successfully
generated. Microcephalin 1 (MCPH1) is implicated in the evolution of the human
brain, and MCPH1 mutation causes microcephaly accompanied by mental retardation.
Here we generated a cynomolgus monkey (Macaca fascicularis) carrying biallelic
MCPH1 mutations using transcription activator-like effector nucleases. The monkey
recapitulated most of the important clinical features observed in patients,
including marked reductions in head circumference, premature chromosome
condensation (PCC), hypoplasia of the corpus callosum and upper limb spasticity.
Moreover, overexpression of MCPH1 in mutated dermal fibroblasts rescued the PCC
syndrome. This monkey model may help us elucidate the role of MCPH1 in the
pathogenesis of human microcephaly and better understand the function of this
protein in the evolution of primate brain size.
PMID- 27502027
TI - Discriminative stimulus properties of 1.25mg/kg clozapine in rats: Mediation by
serotonin 5-HT2 and dopamine D4 receptors.
AB - The atypical antipsychotic drug clozapine remains one of most effective
treatments for schizophrenia, given a lack of extrapyramidal side effects,
improvements in negative symptoms, cognitive impairment, and in symptoms in
treatment-resistant schizophrenia. The adverse effects of clozapine, including
agranulocytosis, make finding a safe clozapine-like a drug a goal for drug
developers. The drug discrimination paradigm is a model of interoceptive stimulus
that has been used in an effort to screen experimental drugs for clozapine-like
atypical antipsychotic effects. The present study was conducted to elucidate the
receptor-mediated stimulus properties that form this clozapine discriminative cue
by testing selective receptor ligands in rats trained to discriminate a 1.25mg/kg
dose of clozapine from vehicle in a two choice drug discrimination task. Full
substitution occurred with the 5-HT2A inverse agonist M100907 and the two
preferential D4/5-HT2/alpha1 receptor antagonists Lu 37-114 ((S)-1-(3-(2-(4-(1H
indol-5-yl)piperazin-1-yl)ethyl)indolin-1-yl)ethan-1-one) and Lu 37-254 (1-(3-(4
(1H-indol-5-yl)piperazin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one). Partial
substitution occurred with the D4 receptor antagonist Lu 38-012 and the alpha1
adrenoceptor antagonist prazosin. Drugs selective for 5-HT2C, 5-HT6 muscarinic,
histamine H1, and benzodiazepine receptors did not substitute for clozapine. The
present findings suggest that 5-HT2A inverse agonism and D4 receptor antagonism
mediate the discriminative stimulus properties of 1.25mg/kg clozapine in rats,
and further confirm that clozapine produces a complex compound discriminative
stimulus.
PMID- 27502028
TI - Grey matter density decreases as well as increases in patients with classic
galactosemia: A voxel-based morphometry study.
AB - Brain impairments have been observed in patients with classic galactosemia, an
inherited metabolic disorder resulting in a particular neuro-cognitive profile.
Neuroimaging studies showed abnormalities such as diffuse white mater (WM)
abnormalities and grey matter (GM) atrophy. Our current study analysed grey
matter density using voxel-based morphometry (VBM) and compared the brains of
eight adolescent patients with classic galactosemia with eight healthy gender-
and aged-matched controls. GM density differences were found in several regions.
Decreased GM density was found in the patients in the bilateral putamen and
bilateral occipital cortex. Increased GM density in the patients, on the other
hand, was found in the bilateral inferior frontal and medial prefrontal cortex.
The anatomical profile of the abnormalities is in line with the neuro-cognitive
profile of patients with classic galactosemia, including motor dysfunction,
speech and language difficulties and higher order cognitive problems. Less
favourable GM densities in patients (either increased or decreased compared to
controls) correlated with younger age, a worse visual working memory performance,
and an older age at initiation of the galactose-restricted diet. To conclude,
this explorative study is the first to analyse the GM using VBM in this
population, and demonstrates a mixed profile of both increased and decreased GM
density in these patients.
PMID- 27502029
TI - Behavioral evidence for the interaction between cannabinoids and Catha edulis F.
(Khat) in mice.
AB - Several studies have shown the existence of an interaction between the
endocannabinoid system and some drugs of abuse, such as opioids, nicotine,
alcohol, and cocaine. For instance, the endocannabinoid system has long been
known to play a role in the underlying mechanisms of drug reward and dependence.
The aim of this study was to evaluate the possible existence of an interaction
between the endocannabinoid system and khat after acute administration.
Behavioral interactions of khat extract with cannabinoids were assessed. To this
effect, mice were randomly divided into different groups (vehicle, khat extract,
khat and WIN55,212-2, a cannabinoid agonist, khat extract and cannabinoid
antagonists, AM251 & AM630) and their behavioral responses were evaluated in
activity monitor, elevated plus maze and Y-maze tests. These tests were used to
determine changes in locomotor activity, anxiety-like behavior, and working
memory. Khat and WIN55,212-2 demonstrated differential responses in these tests,
but co-administration of these agents invariably increased the measured
parameters, which were reversed by the cannabinoid receptor antagonists used. The
data collectively indicate that there is an interaction between khat and the
endocannabinoid system, which most likely involves the cannabinoid receptors or a
common mechanism separately activated by the two agents.
PMID- 27502030
TI - Change in atmospheric deposition during last half century and its impact on
lichen community structure in Eastern Himalaya.
AB - Climatic fluctuations largely affects species turnover and cause major shifts of
terrestrial ecosystem. In the present study the five decade old herbarium
specimens of lichens were compared with recent collection from Darjeeling
district with respect to elements, PAHs accumulation and carbon isotope
composition (delta(13)C) to explore the changes in climatic conditions and its
impact on lichen flora. The delta(13)C has increased in recent specimens which is
in contrast to the assumption that anthropogenic emission leads to delta(13)C
depletion in air and increased carbon discrimination in flora. Study clearly
demonstrated an increase in anthropogenic pollution and drastic decrease in
precipitation while temperature showed abrupt changes during the past five
decades resulting in significant change in lichen community structure. The
Usneoid and Pertusorioid communities increased, while Physcioid and Cyanophycean
decreased, drastically. Lobarian abolished from the study area, however,
Calcicoid has been introduced in the recent past. Probably, post-industrial
revolution, the abrupt changes in the environment has influenced CO2 diffusion
and/C fixation of (lower) plants either as an adaptation strategy or due to
toxicity of pollutants. Thus, the short term studies (<=5 decades) might reflect
recent micro-environmental condition and lichen community structure can be used
as model to study the global climate change.
PMID- 27502031
TI - Heart failure following cancer treatment: characteristics, survival and mortality
of a linked health data analysis.
AB - BACKGROUND: Cardiotoxicity resulting in heart failure is a devastating
complication of cancer therapy. A patient may survive cancer only to develop
heart failure (HF), which has a higher mortality rate than some cancers. AIM:
This study aimed to describe the characteristics and outcomes of HF in patients
with blood or breast cancer after chemotherapy treatment. METHODS: Queensland
Cancer Registry, Death Registry and Hospital Administration records were linked
(1996-2009). Patients were categorised as those with an index HF admission (that
occurred after cancer diagnosis) and those without an index HF admission (non
HF). RESULTS: A total of 15 987 patients was included, and 1062 (6.6%) had an
index HF admission. Median age of HF patients was 67 years (interquartile range
58-75) versus 54 years (interquartile range 44-64) for non-HF patients. More men
than women developed HF (48.6% vs 29.5%), and a greater proportion in the HF
group had haematological cancer (83.1%) compared with breast cancer (16.9%).
After covariate adjustment, HF patients had increased mortality risk compared
with non-HF patients (hazard ratios 1.67 (95% confidence interval, 1.54-1.81)),
and 47% of the index HF admission occurred within 1 year from cancer diagnosis
and 70% within 3 years. CONCLUSION: Cancer treatment may place patients at a
greater risk of developing HF. The onset of HF occurred soon after chemotherapy,
and those who developed HF had a greater mortality risk.
PMID- 27502032
TI - Cardiovascular and Skeletal-related Events Following Localized Prostate Cancer
Treatment: Role of Surgery, Radiotherapy, and Androgen Deprivation.
AB - OBJECTIVE: To examine the impact of androgen deprivation therapy (ADT) and
primary treatment modality on cardiovascular and skeletal-related events and to
investigate potential effect modification in a contemporary cohort of patients
treated for clinically localized prostate cancer. SUBJECTS AND METHODS: We
conducted a retrospective cohort study using Surveillance, Epidemiology, and End
Results-Medicare linked databases for men aged 65-79 years who underwent radical
prostatectomy or radiotherapy for cT1 or cT2 prostate cancer from 2000 to 2008.
We categorized treatment according to primary therapy and receipt of ADT. We
described the cumulative incidence of cardiovascular and skeletal-related events.
RESULTS: Among 60,156 men, 14,403 underwent surgery and 45,753 underwent
radiotherapy. Median follow-up was 6.0 years. After adjusting for baseline
differences, treatments with radiotherapy (adjusted hazard ratios [aHR] 1.16
1.28, P <.0001-.04) and ADT (aHR 1.18-1.32, P <.0001-.008) were each
independently associated with increased risk of coronary heart disease, sudden
cardiac death, fracture, and fracture requiring hospitalization. Radiotherapy was
associated with an increased risk of myocardial infarction (aHR 1.20, P = .02),
whereas ADT was not (P = .5). We did not identify a significant statistical
interaction between primary and hormonal treatment. CONCLUSION: Care for
cardiovascular and skeletal-related events is an important part of the
survivorship phase for a significant proportion of patients with localized
prostate cancer. Increasing use of ADT for patients with localized disease
undergoing radiotherapy and the observed higher prevalence of these events in
these patients should be considered when discussing the risks and benefits of
treatment for localized prostate cancer and when formulating a survivorship plan.
PMID- 27502034
TI - Tunable High-Field Magnetization in Strongly Exchange-Coupled Freestanding Co/CoO
Core/Shell Coaxial Nanowires.
AB - The exchange bias properties of Co/CoO coaxial core/shell nanowires were
investigated with cooling and applied fields perpendicular to the wire axis. This
configuration leads to unexpected exchange-bias effects. First, the magnetization
value at high fields is found to depend on the field-cooling conditions. This
effect arises from the competition between the magnetic anisotropy and the Zeeman
energies for cooling fields perpendicular to the wire axis. This allows
imprinting predefined magnetization states to the antiferromagnetic (AFM) shell,
as corroborated by micromagnetic simulations. Second, the system exhibits a high
field magnetic irreversibility, leading to open hysteresis loops attributed to
the AFM easy axis reorientation during the reversal (effect similar to athermal
training). A distinct way to manipulate the high-field magnetization in exchange
biased systems, beyond the archetypical effects, was thus experimentally and
theoretically demonstrated.
PMID- 27502033
TI - An Important Mimic of Inguinal Hernia.
AB - Spermatic cord malignancy is a rare and challenging diagnosis, often misdiagnosed
as an inguinal hernia or cord lipoma. In these images, we show a 61-year-old male
for whom laparoscopic repair of clinically diagnosed hernia was attempted.
Laparoscopy revealed closed internal ring without hernia. Imaging showed large
paratesticular mass; radical inguinal excision of testicle, cord, and mass was
performed. Pathology showed mixed low-grade and high-grade sarcoma. Liposarcoma
should be considered in cases of unusual inguinal mass; appropriate imaging can
guide surgical approach and optimize outcomes.
PMID- 27502035
TI - beta-arrestins regulate gonadotropin receptor-mediated cell proliferation and
apoptosis by controlling different FSHR or LHCGR intracellular signaling in the
hGL5 cell line.
AB - Gonadotropin signaling classically involves proliferative, steroidogenic and
apoptotic stimuli. In this study, we used the human granulosa cell line hGL5 to
demonstrate how follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
differently control proliferative or apoptotic signals, revealing novel intrinsic
properties of their receptors (FSHR, LHCGR). We found that, in this tumor-like
cell line, the expression of endogenous FSHR and LHCGR is serum-dependent, but
both receptors were unable to activate the canonical cAMP/PKA pathway upon
gonadotropin stimulation, failing to produce cAMP, progesterone and G protein
coupled receptor (GPCR)-mediated apoptosis in vitro. Conversely, ligand treatment
resulted in FSHR- and LHCGR-mediated ERK1/2 phosphorylation and cell
proliferation due to receptor coupling to beta-arrestins. The inactive cAMP/PKA
pathway was unlocked by siRNA-mediated knock-down of beta-arrestin 1 and 2,
leading to progesterone synthesis and apoptosis. Surprisingly, FSH, but not LH
treatment accelerated the cAMP/PKA-mediated apoptosis after beta-arrestin
silencing, an effect which could be reproduced by overexpressing the FSHR, but
not the LHCGR. This work demonstrates that the expression of FSHR and LHCGR can
be induced in hGL5 cells but that the FSHR-dependent cAMP/PKA pathway is
constitutively silenced, possibly to protect cells from FSHR-cAMP-PKA-induced
apoptosis. Also, we revealed previously unrecognized features intrinsic to the
two structurally similar gonadotropin receptors, oppositely resulting in the
regulation of life and death signals in vitro.
PMID- 27502036
TI - LH and FSH promote migration and invasion properties of a breast cancer cell line
through regulatory actions on the actin cytoskeleton.
AB - Reproductive hormones influence breast cancer development and progression. While
the actions of sex steroids in this setting are established, tentative evidence
suggests that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may
also play a role, yet this remains elusive. We here identify that T-47D breast
cancer cells express functional receptors for FSH and LH, and that these hormones
regulate breast cancer cell motility and invasion through the control of the
actin cytoskeleton and the formation of cortical actin aggregates and focal
adhesion complexes. Such actions are mediated by the cytoskeletal controllers
Moesin and focal adhesion kinase (FAK). Moesin is recruited rapidly by FSH and LH
through a signaling cascade requiring the G protein Galpha13 and the Rho
associated kinase, ROCK-2. FSH and LH activate FAK via a Galphai/beta and c-Src
dependent signaling cascade. Both cascades involve signaling to
phosphatidylinositol-3 kinase and Akt. FSH and LH receptors and the related
signaling intermediates are necessary for the actions of gonadotrophins on breast
cancer cell cytoskeletal rearrangement, migration and invasion. These findings
provide original information on the actions of gonadotrophins on breast cancer
cells and may have clinical implications for the use of drugs that modulate
gonadotrophins in breast cancer patients.
PMID- 27502037
TI - Targeted next generation sequencing approach identifies eighteen new candidate
genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome.
AB - The genetic basis is unknown for ~60% of normosmic hypogonadotropic hypogonadism
(nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients
were analyzed by targeted next generation sequencing (NGS) of 261 genes involved
in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome
rearrangements. Selected variants were subjected to Sanger DNA sequencing, the
gold standard. The frequency of Sanger-confirmed variants was determined using
the ExAC database. Variants were classified as likely pathogenic (frameshift,
nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two
novel FGFR1 mutations were identified, as were 18 new candidate genes including:
AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2,
PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic
variants were found in 8/48 (16.7%) and 1/48 (2.1%) patients, respectively. NGS
with confirmation by Sanger sequencing resulted in the identification of new
causative FGFR1 gene mutations and suggested 18 new candidate genes in nHH/KS.
PMID- 27502038
TI - Dilated cavum septi pellucidi in fetuses with microdeletion 22q11.
AB - OBJECTIVES: The cavum septi pellucidi (CSP) is an easily recognizable landmark in
the fetal brain. CSP disappears after birth to form the septum pellucidum.
Children with microdeletion 22q11 (del. 22q11) were, however, reported to have a
persistent dilated CSP. This study was designed to examine whether the CSP is
dilated in fetuses with del.22q11. METHODS: This was a case-control study where
the CSP width was measured in normal fetuses from 16 to 34 weeks and in fetuses
with del. 22q11. CSP width was correlated to the biparietal diameter (BPD).
Reference curves were constructed, and z-scores calculated. RESULTS: Cavum septi
pellucidi width in 260 normal fetuses showed a linear correlation with BPD. The
study group consisted of 37 fetuses with del. 22q11. In 25/37 (67.5%) of fetuses
with del. 22q11, the CSP was enlarged with a mean z-score of 2.64 (p < 0.0001).
Fetuses with a BPD > 50 mm (>22 weeks of gestation) had a dilated CSP in 85.7%
(24/28). CONCLUSIONS: The CSP is a structure routinely evaluated in screening
ultrasound. A wide CSP is found in second trimester fetuses with del. 22q11. A
dilated CSP may be an important sonographic marker for the presence of del. 22q11
along with conotruncal malformations and thymic hypoplasia. (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27502039
TI - Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool
Predominantly via the Activation of the Notch Self-Renewal Pathway.
AB - An emerging dogma shows that tumors are initiated and maintained by a
subpopulation of cancer cells that hijack some stem cell features and thus
referred to as "cancer stem cells" (CSCs). The exact mechanism that regulates the
maintenance of CSC pool remains largely unknown. Fascin is an actin-bundling
protein that we have previously demonstrated to be a major regulator of breast
cancer chemoresistance and metastasis, two cardinal features of CSCs. Here, we
manipulated fascin expression in breast cancer cell lines and used several in
vitro and in vivo approaches to examine the relationship between fascin
expression and breast CSCs. Fascin knockdown significantly reduced stem cell-like
phenotype (CD44hi /CD24lo and ALDH+ ) and reversal of epithelial to mesenchymal
transition. Interestingly, expression of the embryonic stem cell transcriptional
factors (Oct4, Nanog, Sox2, and Klf4) was significantly reduced when fascin
expression was down-regulated. Functionally, fascin-knockdown cells were less
competent in forming colonies and tumorspheres, consistent with lower basal self
renewal activity and higher susceptibility to chemotherapy. Fascin effect on CSC
chemoresistance and self-renewability was associated with Notch signaling.
Activation of Notch induced the relevant downstream targets predominantly in the
fascin-positive cells. Limiting-dilution xenotransplantation assay showed higher
frequency of tumor-initiating cells in the fascin-positive group. Collectively,
our data demonstrated fascin as a critical regulator of breast CSC pool at least
partially via activation of the Notch self-renewal signaling pathway and
modification of the expression embryonic transcriptional factors. Targeting
fascin may halt CSCs and thus presents a novel therapeutic approach for effective
treatment of breast cancer. Stem Cells 2016;34:2799-2813 Video Highlight:
https://youtu.be/GxS4fJ_Ow-o.
PMID- 27502040
TI - Tetracycline marks visible in Baltic cod Gadus morhua otoliths stored for 40
years.
AB - Baltic cod Gadus morhua otoliths marked with oxytetracycline (OTC) in 1974-1975
had been sectioned and the sections stored in paper envelopes at room temperature
in dry, dark conditions. After 40 years of storage, the historic OTC marks were
still clearly visible showing that OTC is suitable for long-term chemical marking
of otoliths. They were, however, noticeably paler than marks in recently
recaptured and archived Baltic G. morhua otoliths, chemically tagged with
tetracycline at similar dosage to the historic otoliths.
PMID- 27502041
TI - Identification of nontuberculous mycobacteria in MGIT by matrix-assisted laser
desorption/ionization mass spectrometry.
AB - AIM: The performance of Bruker Biotyper matrix-assisted laser
desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in
identifying species of nontuberculous mycobacteria (NTM) in flagged Mycobacteria
Growth Indicator Tubes (MGIT)s is unclear. MATERIALS & METHODS: A total of 92
sequential MGIT-positive nontuberculous mycobacteria isolates, including
Mycobacterium intracellulare, M. abscessus complex, M. avium complex and M.
avium, were used to compare the performance of the MALDI-TOF MS for species-level
identification with that of the BluePoint MycoID plus kit and final
identification. RESULTS: A total of 44 (47.8%) and 80 (87.0%) isolates were
correctly identified to the species level by the MALDI-TOF MS and BluePoint
MycoID plus kit, respectively. CONCLUSION: The procedure of MALDI-TOF MS in MGITs
inoculated with clinical specimens is needed to be further optimized.
PMID- 27502042
TI - Three-Dimensional Transthoracic Echocardiography in the Comprehensive Evaluation
of Right and Left Heart Chamber Remodeling Following Percutaneous Mitral Valve
Repair.
AB - BACKGROUND: Percutaneous mitral valve repair (PMVR) is an alternative treatment
in patients with significant mitral regurgitation (MR) who are denied surgery.
Although in surgical patients, outcomes have been related both to acute
hemodynamic favorable results and to positive cardiac remodeling in the midterm,
in the case of PMVR the effect on cardiac chamber remodeling has never been
extensively studied. The aims of this study were (1) to evaluate the short- and
mid-term remodeling induced by PMVR on cardiac chamber volume using two- and
three-dimensional (3D) transthoracic echocardiographic (TTE) imaging and (2) to
assess changes in left ventricular (LV) shape on the basis of 3D TTE data.
METHODS: Patients undergoing PMVR were prospectively enrolled. Two-dimensional
and 3D TTE data sets acquired at baseline, and at 30 days and 6 months after PMVR
were analyzed to assess LV and right ventricular (RV) volumes and ejection
fraction and left atrial and right atrial volumes. Moreover, 3D endocardial
surfaces were extracted to compute 3D shape indexes of LV sphericity and conicity
at end-diastole and end-systole. RESULTS: Six of the 64 enrolled patients did not
reach follow-up and were excluded. The analysis was feasible in all 58 patients
considered (26 with functional MR and 32 [55%] with degenerative MR). PMVR
resulted in significant reduction of MR and in favorable remodeling: (1)
effective PMVR was mainly associated with decreased LV loading, (2) PMVR-related
reverse remodeling was observed in patients with degenerative MR and those with
functional MR at 30 days and continued at 6-month follow-up, (3) favorable
remodeling in LV shape from abnormally spherical to more normal conical took
place in both groups after PMVR, and (4) RV volumes and systolic function were
preserved after PMVR. CONCLUSIONS: A comprehensive two-dimensional and 3D TTE
analysis allows investigation from a double perspective (volume and morphology)
of the entity and modality of changes following PMVR. In high-risk patients
undergoing PMVR, postprocedural heart remodeling involves all cardiac chambers,
occurs in the short term, and further improves at midterm follow-up.
PMID- 27502043
TI - Two angiotensin-converting enzyme-inhibitory peptides from almond protein and the
protective action on vascular endothelial function.
AB - This study aimed to discover and prepare novel angiotensin converting enzyme
(ACE) inhibitory peptides from almond protein and further evaluate the effect on
endothelial function of human umbilical vascular endothelial cells (HUVECs).
Almond protein was hydrolyzed using a two-stage alcalase-protamex hydrolysis
process, and the hydrolysates were subjected to a series of separations,
ultrafiltration, gel filtration chromatography, and reversed-phased preparative
chromatography, to obtain the active peptides. Seven ACE inhibitory fractions
with the molecular weight below 1.5 kDa were isolated and prepared, and two
purified ACE inhibitory peptides with the IC50 values of 67.52 +/- 0.05 and 43.18
+/- 0.07 MUg mL(-1), were identified as Met-His-Thr-Asp-Asp and Gln-His-Thr-Asp
Asp, respectively. Then the effect of two ACE inhibitory peptides on the
endothelial function of HUVECs was evaluated. Results showed that the two potent
ACE inhibitory peptides significantly regulated the release of nitric oxide and
endothelin in HUVECs. These results suggest that almond peptides have potential
as an antihypertensive nutraceuticals or a functional food ingredient.
PMID- 27502044
TI - Energies and densities of electrons confined in elliptical and ellipsoidal
quantum dots.
AB - We consider a droplet of electrons confined within an external harmonic potential
well of elliptical or ellipsoidal shape, a geometry commonly encountered in work
with semiconductor quantum dots and other nanoscale or mesoscale structures. For
droplet sizes exceeding the effective Bohr radius, the dominant contribution to
average system parameters in the Thomas-Fermi approximation comes from the
potential energy terms, which allows us to derive expressions describing the
electron droplet's shape and dimensions, its density, total and capacitive
energy, and chemical potential. The analytical results are in very good agreement
with experimental data and numerical calculations, and make it possible to follow
the dependence of the properties of the system on its parameters (the total
number of electrons, the axial ratios and curvatures of the confinement
potential, and the dielectric constant of the material). An interesting feature
is that the eccentricity of the electron droplet is not the same as that of its
confining potential well.
PMID- 27502045
TI - A new lizard malaria parasite Plasmodium intabazwe n. sp. (Apicomplexa:
Haemospororida: Plasmodiidae) in the Afromontane Pseudocordylus melanotus
(Sauria: Cordylidae) with a review of African saurian malaria parasites.
AB - BACKGROUND: Saurian malaria parasites are diverse apicomplexan blood parasites
including the family Plasmodiidae Mesnil, 1903, and have been studied since the
early 1900s. Currently, at least 27 species of Plasmodium are recorded in African
lizards, and to date only two species, Plasmodium zonuriae (Pienaar, 1962) and
Plasmodium cordyli Telford, 1987, have been reported from the African endemic
family Cordylidae. This paper presents a description of a new malaria parasite in
a cordylid lizard and provides a phylogenetic hypothesis for saurian Plasmodium
species from South Africa. Furthermore, it provides a tabular review of the
Plasmodium species that to date have been formally described infecting species of
African lizards. METHODS: Blood samples were collected from 77 specimens of
Pseudocordylus melanotus (A. Smith, 1838) from Platberg reserve in the Eastern
Free State, and two specimens of Cordylus vittifer (Reichenow, 1887) from the
Roodewalshoek conservancy in Mpumalanga (South Africa). Blood smears were Giemsa
stained, screened for haematozoa, specifically saurian malaria parasites,
parasite stages were photographed and measured. A small volume was also preserved
for TEM studies. Plasmodium and Haemoproteus primer sets, with a nested
polymerase chain reaction (PCR) protocol, were employed to target a fragment of
the cytochrome-b (cyt-b) gene region. Resulting sequences of the saurian
Plasmodium species' isolates were compared with each other and to other known
Plasmodium spp. sequences in the GenBank database. RESULTS: The presence of P.
zonuriae in both specimens of the type lizard host C. vittifer was confirmed
using morphological characteristics, which subsequently allowed for the species'
molecular characterisation. Of the 77 P. melanotus, 44 were parasitised by a
Plasmodium species, which when compared morphologically to other African saurian
Plasmodium spp. and molecularly to P. zonuriae, supported its description as a
new species Plasmodium intabazwe n. sp. CONCLUSIONS: This is the first
morphological and molecular account of Plasmodium species within the African
endemic family Cordylidae from South Africa. The study highlights the need for
molecular analysis of other cordylid Plasmodium species within Africa. Future
studies should also include elucidating of the life-cycles of these species, thus
promoting the use of both morphological and molecular characteristics in species
descriptions of saurian malaria parasites.
PMID- 27502046
TI - Cerebral responses to local and global auditory novelty under general anesthesia.
AB - Primate brains can detect a variety of unexpected deviations in auditory
sequences. The local-global paradigm dissociates two hierarchical levels of
auditory predictive coding by examining the brain responses to first-order
(local) and second-order (global) sequence violations. Using the macaque model,
we previously demonstrated that, in the awake state, local violations cause focal
auditory responses while global violations activate a brain circuit comprising
prefrontal, parietal and cingulate cortices. Here we used the same local-global
auditory paradigm to clarify the encoding of the hierarchical auditory
regularities in anesthetized monkeys and compared their brain responses to those
obtained in the awake state as measured with fMRI. Both, propofol, a GABAA
agonist, and ketamine, an NMDA-antagonist, left intact or even enhanced the
cortical response to auditory inputs. The local effect vanished during propofol
anesthesia and shifted spatially during ketamine anesthesia compared with
wakefulness. Under increasing levels of propofol, we observed a progressive
disorganization of the global effect in prefrontal, parietal and cingulate
cortices and its complete suppression under ketamine anesthesia. Anesthesia also
suppressed thalamic activations to the global effect. These results suggest that
anesthesia preserves initial auditory processing, but disturbs both short-term
and long-term auditory predictive coding mechanisms. The disorganization of
auditory novelty processing under anesthesia relates to a loss of thalamic
responses to novelty and to a disruption of higher-order functional cortical
networks in parietal, prefrontal and cingular cortices.
PMID- 27502047
TI - Calibrated bold fMRI with an optimized ASL-BOLD dual-acquisition sequence.
AB - Calibrated fMRI techniques estimate task-induced changes in the cerebral
metabolic rate of oxygen (CMRO2) based on simultaneous measurements of cerebral
blood flow (CBF) and blood-oxygen-level-dependent (BOLD) signal changes evoked by
stimulation. To determine the calibration factor M (corresponding to the maximum
possible BOLD signal increase), BOLD signal and CBF are measured in response to a
gas breathing challenge (usually CO2 or O2). Here we describe an ASL dual
acquisition sequence that combines a background-suppressed 3D-GRASE readout with
2D multi-slice EPI. The concatenation of these two imaging sequences allowed
separate optimization of the acquisition for CBF and BOLD data. The dual
acquisition sequence was validated by comparison to an ASL sequence with a dual
echo EPI readout, using a visual fMRI paradigm. Results showed a 3-fold increase
in temporal signal-to-noise ratio (tSNR) of the ASL time-series data while BOLD
tSNR was similar to that obtained with the dual-echo sequence. The longer TR of
the proposed dual-acquisition sequence, however, resulted in slightly lower T
scores (by 30%) in the BOLD activation maps. Further, the potential of the dual
acquisition sequence for M-mapping on the basis of a hypercapnia gas breathing
challenge and for quantification of CMRO2 changes in response to a motor
activation task was assessed. In five subjects, an average gray matter M-value of
8.71+/-1.03 and fractional changes of CMRO2 of 12.5+/-5% were found. The new
sequence remedies the deficiencies of prior combined BOLD-ASL acquisition
strategies by substantially enhancing perfusion tSNR, which is essential for
accurate BOLD calibration.
PMID- 27502049
TI - Regional homogeneity of intrinsic brain activity correlates with auditory-motor
processing of vocal pitch errors.
AB - It has been well documented that speakers produce rapid compensatory vocal
adjustments for errors they perceive in their auditory feedback. The fact that
they differ greatly in the degree to which they compensate for perceived errors,
however, has received much less attention. The present study investigated whether
intrinsic brain activity during resting can predict an individual's behavioral
and cortical responses in compensating for pitch-shifted auditory feedback during
vocalization. This relationship was investigated by correlating the regional
homogeneity (ReHo) of resting-state fMRI signals with the vocal compensation and
event-related potentials (N1 and P2) in response to pitch shifts of -200 and -500
cents. Behaviorally, the magnitudes of vocal compensation were significantly
correlated with the ReHo values in the right supplementary motor area (SMA) for
both -200 and -500 cents, the right primary motor cortex (M1) for -200 cents, and
the left premotor cortex (PMC) for -500 cents. For both pitch shift sizes, there
were significant correlations between ReHo and N1 amplitude in the left inferior
frontal gyrus (IFG), right superior temporal gyrus (STG), bilateral M1, and left
SMA. Significant correlations between ReHo and P2 amplitude were observed in the
bilateral IFG, right STG, left SMA and M1 for -200 and -500 cents, the left PMC
for -200 cents, and the right SMA for -500 cents. These findings provide the
first evidence that regional homogeneity of intrinsic brain activity can predict
behavioral and cortical responses in compensating for pitch errors in voice
auditory feedback.
PMID- 27502050
TI - Diabetes in Rats Is Cured by Islet Transplantation...But Only During Daytime.
PMID- 27502048
TI - Ten problems and solutions when predicting individual outcome from lesion site
after stroke.
AB - In this paper, we consider solutions to ten of the challenges faced when trying
to predict an individual's functional outcome after stroke on the basis of lesion
site. A primary goal is to find lesion-outcome associations that are consistently
observed in large populations of stroke patients because consistent associations
maximise confidence in future individualised predictions. To understand and
control multiple sources of inter-patient variability, we need to systematically
investigate each contributing factor and how each factor depends on other
factors. This requires very large cohorts of patients, who differ from one
another in typical and measurable ways, including lesion site, lesion size,
functional outcome and time post stroke (weeks to decades). These multivariate
investigations are complex, particularly when the contributions of different
variables interact with one another. Machine learning algorithms can help to
identify the most influential variables and indicate dependencies between
different factors. Multivariate lesion analyses are needed to understand how the
effect of damage to one brain region depends on damage or preservation in other
brain regions. Such data-led investigations can reveal predictive relationships
between lesion site and outcome. However, to understand and improve the
predictions we need explanatory models of the neural networks and degenerate
pathways that support functions of interest. This will entail integrating the
results of lesion analyses with those from functional imaging (fMRI, MEG),
transcranial magnetic stimulation (TMS) and diffusor tensor imaging (DTI) studies
of healthy participants and patients.
PMID- 27502051
TI - Investigating the association between photosynthetic efficiency and generation of
biophotoelectricity in autotrophic microbial fuel cells.
AB - Microbial fuel cells operating with autotrophic microorganisms are known as
biophotovoltaic devices. It represents a great opportunity for environmentally
friendly power generation using the energy of the sunlight. The efficiency of
electricity generation in this novel system is however low. This is partially
reflected by the poor understanding of the bioelectrochemical mechanisms behind
the electron transfer from these microorganisms to the electrode surface. In this
work, we propose a combination of electrochemical and fluorescence techniques,
giving emphasis to the pulse amplitude modulation fluorescence. The combination
of these two techniques allow us to obtain information that can assist in
understanding the electrical response obtained from the generation of electricity
through the intrinsic properties related to the photosynthetic efficiency that
can be obtained from the fluorescence emitted. These were achieved quantitatively
by means of observed changes in four photosynthetic parameters with the bioanode
generating electricity. These are the maximum quantum yield (Fv/Fm), alpha
(alpha), light saturation coefficient (Ek) and maximum rate of electron transfer
(rETRm). The relationship between the increases in the current density collected
by the bioanode to the decrease of the rETRm values in the photosynthetic pathway
for the two microorganisms was also discussed.
PMID- 27502052
TI - Dimerization of Arginyl-tRNA Synthetase by Free Heme Drives Its Inactivation in
Plasmodium falciparum.
AB - Excess cellular heme is toxic, and malaria parasites regulate its levels during
hemoglobin digestion. Aminoacyl-tRNA synthetases are ubiquitous enzymes, and of
these, arginyl-tRNA synthetase (RRS) is unique as its enzymatic product of
charged tRNA is required for protein synthesis and degradation. We show that
Plasmodium falciparum arginyl-tRNA synthetase (PfRRS) is an active, cytosolic,
and monomeric enzyme. Its high-resolution crystal structure highlights critical
structural differences with the human enzyme. We further show that hemin binds to
and inhibits the aminoacylation activity of PfRRS. Hemin induces a dimeric form
of PfRRS that is thus rendered enzymatically dead as it is unable to recognize
its cognate tRNA(arg). Excessive hemin in chloroquine-treated malaria parasites
results in significantly reduced charged tRNA(arg) levels, thus suggesting
deceleration of protein synthesis. These data together suggest that the
inhibition of Plasmodium falciparum arginyl-tRNA synthetase can now be synergized
with existing antimalarials for more potent drug cocktails against malaria
parasites.
PMID- 27502053
TI - Wholesome Nutrition: an example for a sustainable diet.
AB - 'Wholesome Nutrition' is a concept of sustainable nutrition that was developed at
the University of Giessen in the 1980s. In this concept, health and the ecologic,
economic, social and cultural dimensions of nutrition are equally important. In
1992 at the UN-Conference on Environment and Development in Rio de Janeiro the
definition of 'Sustainable Development' comprised the dimensions environment,
economy and society. Additionally to these three 'classical' dimensions of
sustainability, we included 'health' as the fourth dimension because nutrition
has far reaching effects on human health. The fifth dimension, 'culture', became
part of the sustainability dialogue since many years; the respective cultural
background influences food habits. Presently, mankind has to cope with huge
global challenges such as poverty and food insecurity in low-income countries as
well as climate change. Therefore the objective is to identify prospects for
actions to respond to these global challenges. The concept of 'Sustainable
Nutrition' analyses the food supply chain at all stages from input-production and
primary production to processing, distribution, preparation, consumption and
waste disposal. The present analysis leads to the following seven principles:
preference of plant-based foods, organic foods, regional and seasonal products,
preference of minimally processed foods, Fair Trade products, resource-saving
housekeeping and enjoyable eating culture. This concept is based on holistic
thinking and has the potential to reduce the global challenges in the field of
nutrition. Scientists, stakeholders, multipliers and consumers are asked to
consider environmental, economic, social and cultural aspects in addition to the
biological (health) aspects.
PMID- 27502055
TI - Ephemeral ecological speciation and the latitudinal biodiversity gradient.
AB - The richness of biodiversity in the tropics compared to high-latitude parts of
the world forms one of the most globally conspicuous patterns in biology, and yet
few hypotheses aim to explain this phenomenon in terms of explicit
microevolutionary mechanisms of speciation and extinction. We link population
genetic processes of selection and adaptation to speciation and extinction by way
of their interaction with environmental factors to drive global scale
macroecological patterns. High-latitude regions are both cradle and grave with
respect to species diversification. In particular, we point to a conceptual
equivalence of "environmental harshness" and "hard selection" as eco-evolutionary
drivers of local adaptation and ecological speciation. By describing how
ecological speciation likely occurs more readily at high latitudes, with such
nascent species especially prone to extinction by fusion, we derive the ephemeral
ecological speciation hypothesis as an integrative mechanistic explanation for
latitudinal gradients in species turnover and the net accumulation of
biodiversity.
PMID- 27502054
TI - Pilot clinical observations between food and drug seeking derived from fifty
cases attending an eating disorder clinic.
AB - Background The reward deficiency syndrome hypothesis posits that genes are
responsible for reward dependence and related behaviors. There is evidence that
both bulimia and anorexia nervosa, especially in women, have been linked to a
lifetime history of substance use disorder (SUD). There are difficulties in
accepting food as an addiction similar to drugs; however, increasingly
neuroimaging studies favor such an assertion. Case presentations We are reporting
the evidence of comorbidity of eating disorders with SUD found within these case
presentations. We show 50 case reports derived from two independent treatment
centers in Florida that suggest the commonality between food and drug addictions.
In an attempt to provide data from this cohort, many participants did not
adequately respond to our questionnaire. Discussion We propose that dopamine
agonist therapy may be of common benefit. Failure in the past may reside in too
powerful D2 agonist activity leading to D2 receptor downregulation, while the new
methodology may cause a reduction of "dopamine resistance" by inducing "dopamine
homeostasis." While this is not a definitive study, it does provide some
additional clinical evidence that these two addictions are not mutually
exclusive. Conclusion Certainly, it is our position that there is an overlap
between food- and drug-seeking behavior. We propose that the studies focused on
an effort to produce natural activation of dopaminergic reward circuitry as a
type of common therapy may certainly be reasonable. Additional research is
warranted.
PMID- 27502056
TI - Comparison of the compatible solute pool of two slightly halophilic
planctomycetes species, Gimesia maris and Rubinisphaera brasiliensis.
AB - Gimesia maris and Rubinisphaera brasiliensis are slightly halophilic
representatives of the deep-branching phylum Planctomycetes. For osmoadaptation
both species accumulated alpha-glutamate, sucrose, ectoine and hydroxyectoine. A
major role was found for ectoine, hydroxyectoine as well as sucrose under hyper
osmotic shock conditions. Nevertheless, the levels of sucrose were up-regulated
by the increased salinity levels and also by low nitrogen availability.
Additionally, G. maris accumulated glucosylglycerate (GG) as major solute
specifically under low nitrogen levels, which prompted us to analyse the
transcript abundance of two homologues genes known for the biosynthesis of GG,
namely glucosyl-3-phosphoglycerate synthase (GpgS) and glucosyl-3
phosphoglycerate phosphatase (GpgP). By qPCR using a suitable reference gene
selected in this study, the transcript abundance of the biosynthetic genes was
quantified in G. maris cells under hyper-osmotic shock or under low nitrogen
conditions. The gpgS gene was induced under nitrogen-limiting conditions
suggesting that GG synthesis is regulated primarily at the transcription level.
Moreover, the expression of a gene coding for a putative sucrose-phosphorylase
(Spase) located upstream the gpgS and gpgP genes was up-regulated, predicting a
metabolic role of Spase probably related to GG synthesis.
PMID- 27502057
TI - Periodontal conditions and incidence of new cardiovascular events among patients
with coronary vascular disease.
AB - AIM: We wanted to investigate whether periodontal conditions and/or oral care
habits are associated with new cardiovascular events among patients with coronary
vascular disease (CVD). MATERIALS AND METHODS: In this longitudinal cohort study,
1002 inpatients with CVD were included. They were examined regarding prevalence
of severe periodontitis, bleeding upon probing (BOP), number of missing teeth and
oral care habits. The combined endpoint was defined as myocardial infarction,
stroke/transient ischaemic attack, cardiovascular death and death caused by
stroke. Survival analyses were carried out after a 3-year follow-up period.
Hazard ratios (HRs) were adjusted for known cardiac risk factors using Cox
regression. RESULTS: Nine hundred and fifty-three patients completed the 3-year
follow-up. The overall incidence of the combined endpoint was 16.4%. Significant
HRs for BOP (HR = 2, 95% CI: 1.2-3.3), severe tooth loss (HR = 1.8, 95% CI: 1.3
2.5), brushing teeth more than once a day (HR = 0.6, 95% CI: 0.5-1.0) and use of
floss/inter-dental brushes (HR = 0.5, 95% CI: 0.3-0.9) were evaluated only in
univariate but not in multivariate survival analyses. Patients with severe
periodontitis achieved the combined endpoint more often (18.9% versus 14.2%), but
the result was not statistically significant after both univariate and
multivariate survival analyses. CONCLUSIONS: Periodontal conditions and oral care
habits are not independent indicators for further adverse events in patients with
CVD.
PMID- 27502058
TI - Anthracycline-Associated T1 Mapping Characteristics Are Elevated Independent of
the Presence of Cardiovascular Comorbidities in Cancer Survivors.
AB - BACKGROUND: Cardiovascular magnetic resonance T1 mapping characteristics are
elevated in adult cancer survivors; however, it remains unknown whether these
elevations are related to age or presence of coincident cardiovascular
comorbidities. METHODS AND RESULTS: We performed blinded cardiovascular magnetic
resonance analyses of left ventricular T1 and extracellular volume (ECV) fraction
in 327 individuals (65% women, aged 64+/-12 years). Thirty-seven individuals had
breast cancer or a hematologic malignancy but had not yet initiated their
treatment, and 54 cancer survivors who received either anthracycline-based (n=37)
or nonanthracycline-based (n=17) chemotherapy 2.8+/-1.3 years earlier were
compared with 236 cancer-free participants. Multivariable analyses were performed
to determine the association between T1/ECV measures and variables associated
with myocardial fibrosis. Age-adjusted native T1 was elevated pre- (1058+/-7 ms)
and post- (1040+/-7 ms) receipt of anthracycline chemotherapy versus comparators
(965+/-3 ms; P<0.0001 for both). Age-adjusted ECV, a marker of myocardial
fibrosis, was elevated in anthracycline-treated cancer participants (30.4+/-0.7%)
compared with either pretreatment cancer (27.8+/-0.7%; P<0.01) or cancer-free
comparators (26.9+/-0.2%; P<0.0001). T1 and ECV of nonanthracycline survivors
were no different than pretreatment survivors (P=0.17 and P=0.16, respectively).
Native T1 and ECV remained elevated in cancer survivors after accounting for
demographics (including age), myocardial fibrosis risk factors, and left
ventricular ejection fraction or myocardial mass index (P<0.0001 for all).
CONCLUSIONS: Three years after anthracycline-based chemotherapy, elevations in
myocardial T1 and ECV occur independent of underlying cancer or cardiovascular
comorbidities, suggesting that imaging biomarkers of interstitial fibrosis in
cancer survivors are related to prior receipt of a potentially cardiotoxic cancer
treatment regimen.
PMID- 27502059
TI - Moderate Physical Activity in Healthy Adults Is Associated With Cardiac
Remodeling.
AB - BACKGROUND: Cardiac mass and volumes are often elevated in athletes, but it is
not known whether moderate physical activity is also associated with cardiac
dilatation and hypertrophy in a healthy adult population. METHODS AND RESULTS: In
total, 1096 adults (54% female, median age 39 years) without cardiovascular
disease or cardiomyopathy-associated genetic variants underwent cardiac magnetic
resonance imaging to determine biventricular volumes and function. Physical
activity was assessed using a validated activity questionnaire. The relationship
between cardiac parameters and activity was assessed using multiple linear
regression adjusting for age, sex, race, and systolic blood pressure. Logistic
regression was performed to determine the effect of activity on the likelihood of
subjects having cardiac dilatation or hypertrophy according to standard cardiac
magnetic resonance normal ranges. Increasing physical activity was associated
with greater left ventricular (LV) mass (beta=0.23; P<0.0001) and elevated LV and
right ventricular volumes (LV: beta=0.26, P<0.0001; right ventricular: beta=0.26,
P<0.0001). Physical activity had a larger effect on cardiac parameters than
systolic blood pressure (0.06<=beta<=0.21) and a similar effect to age (
0.20<=beta<=-0.31). Increasing physical activity was a risk factor for meeting
imaging criteria for LV hypertrophy (adjusted odds ratio 2.1; P<0.0001), LV
dilatation (adjusted odds ratio 2.2; P<0.0001), and right ventricular dilatation
(adjusted odds ratio 2.2; P<0.0001). CONCLUSIONS: Exercise-related cardiac
remodeling is not confined to athletes, and there is a risk of overdiagnosing
cardiac dilatation or hypertrophy in a proportion of active, healthy adults.
PMID- 27502061
TI - Detection of Myocarditis With Molecular Echo Imaging: Another Potential
Application for the Phosphatidyl Serine Microbubble.
PMID- 27502060
TI - Noninvasive Contrast-Enhanced Ultrasound Molecular Imaging Detects Myocardial
Inflammatory Response in Autoimmune Myocarditis.
AB - BACKGROUND: Cardiac tests for diagnosing myocarditis lack sensitivity or
specificity. We hypothesized that contrast-enhanced ultrasound molecular imaging
could detect myocardial inflammation and the recruitment of specific cellular
subsets of the inflammatory response in murine myocarditis. METHODS AND RESULTS:
Microbubbles (MB) bearing antibodies targeting lymphocyte CD4 (MBCD4),
endothelial P-selectin (MBPSel), or isotype control antibody (MBIso) and MB with
a negative electric charge for targeting of leukocytes (MBLc) were prepared.
Attachment of MBCD4 was validated in vitro using murine spleen CD4+ T cells.
Twenty-eight mice were studied after the induction of autoimmune myocarditis by
immunization with alpha-myosin-peptide; 20 mice served as controls. Contrast
enhanced ultrasound molecular imaging of the heart was performed. Left
ventricular function was assessed by conventional and deformation
echocardiography, and myocarditis severity graded on histology. Animals were
grouped into no myocarditis, moderate myocarditis, and severe myocarditis. In
vitro, attachment of MBCD4 to CD4+ T cells was significantly greater than of
MBIso. Of the left ventricular ejection fraction or strain and strain rate
readouts, only longitudinal strain was significantly different from control
animals in severe myocarditis. In contrast, contrast-enhanced ultrasound
molecular imaging showed increased signals for all targeted MB versus MBIso both
in moderate and severe myocarditis, and MBCD4 signal correlated with CD4+ T
lymphocyte infiltration in the myocardium. CONCLUSIONS: Contrast-enhanced
ultrasound molecular imaging can detect endothelial inflammation and leukocyte
infiltration in myocarditis in the absence of a detectable decline in left
ventricular performance by functional imaging. In particular, imaging of CD4+ T
cells involved in autoimmune responses could be helpful in diagnosing
myocarditis.
PMID- 27502062
TI - Exercise-Induced Cardiac Remodeling: Competitive Athletes Are Just the Tip of the
Iceberg.
PMID- 27502063
TI - Anthracycline Cardiotoxicity: How Do We Move From Diagnosis to Prediction?
PMID- 27502064
TI - Streptococcus dysgalactiae subsp. equisimilis Isolated From Infections in Dogs
and Humans: Are Current Subspecies Identification Criteria accurate?
AB - Streptococcus dysgalactiae is a pyogenic species pathogenic both for humans and
animals. Until recently, it has been considered an exclusive animal pathogen
causing infections in wild as well as domestic animals. Currently, human
infections are being reported with increasing frequency, and their clinical
picture is often similar to the ones caused by Streptococcus pyogenes. Due to the
fact that S. dysgalactiae is a heterogeneous species, it was divided into two
subspecies: S. dysgalactiae subsp. equisimilis (SDSE) and S. dysgalactiae subsp.
dysgalactiae (SDSD). The first differentiation criterion, described in 1996, was
based on strain isolation source. Currently applied criteria, published in 1998,
are based on hemolysis type and Lancefield group classification. In this study,
we compared subspecies identification results for 36 strains isolated from
clinical cases both in humans and animals. Species differentiation was based on
two previously described criteria as well as MALDI-TOF and genetic analyses: RISA
and 16S rRNA genes sequencing. Antimicrobial susceptibility profiles were also
determined according to CLSI guidelines. The results presented in our study
suggest that the subspecies differentiation criteria previously described in the
above two literature positions seem to be inaccurate in analyzed group of
strains, the hemolysis type on blood agar, and Lancefield classification should
not be here longer considered as criteria in subspecies identification. The
antimicrobial susceptibility tests indicate emerging of multiresistant human SDSE
strains resistant also to vancomycin, linezolid and tigecycline, which might pose
a substantial problem in treatment.
PMID- 27502065
TI - Evaluation of a Commercial Real-Time PCR Kit for the Detection of Mycobacterium
avium subspecies paratuberculosis in Milk.
AB - There are several commercial test kits for Mycobacterium avium subspecies
paratuberculosis (MAP) detection, each with different advantages, disadvantages,
and applications. In the present study, a real-time PCR kit targeting the unique
transposon sequence ISMAP02 was evaluated. The analytical sensitivity was
determined using the type strain ATCC 19698, and the specificity was validated by
testing fifteen MAP isolates, thirteen non-MAP Mycobacterium isolates, and eight
non-Mycobacterium isolates. Six spiking experiments were performed using raw milk
and reconstituted infant milk artificially contaminated with dilutions containing
10(0)-10(5) MAP cells mL(-1). Sensitivity and specificity were at 100 %. The
detection probabilities in raw milk and reconstituted infant milk for the samples
(containing 1.4 * 10(1) and 1.7 * 10(1) MAP cell 50 mL(-1)) were 16.6 and 91.6 %,
respectively. Thus, the tested kit yielded satisfying results to detect MAP in
milk.
PMID- 27502066
TI - Spirosoma fluminis sp. nov., a Gamma-Radiation Resistant Bacterium Isolated from
Sediment of the Han River in South Korea.
AB - A Gram-negative, long rod-shaped, and yellowish bacterium, designated as strain
15J17T(T), was isolated from sediment of the Han River in South Korea after
exposure to 3 kGy of gamma radiation. The strain was catalase- and oxidase
positive and showed resistance to gamma radiation-D10 value (i.e., the dose
required to reduce the bacterial population by 10-fold) of >4 kGy. Phylogenetic
analysis based on the 16S rRNA gene sequence revealed that the strain belonged to
the genus Spirosoma and showed moderate degrees of sequence similarity with
related species (90.6-93.5 %). Chemotaxonomic data revealed that the strain
contained summed feature 3 (C16:1 omega7c/C16:1 omega6c), C16:1 omega5c, C16:0,
C18:0, and C15:0 iso as the major fatty acids; phosphatidylethanolamine, an
unidentified aminophospholipid, and an unidentified polar lipid as the major
polar lipids; and menaquinone-7 (MK-7) as the major quinone. The genomic DNA G+C
content of the new strain was 48.3 mol%. Based on these data, type strain
15J17T(T) (=KCTC 52198(T) = JCM 31409(T)) should be classified as representing a
new species, for which we propose the name Spirosoma fluminis sp. nov.
PMID- 27502067
TI - Creating a family through connection websites and events: ethical and social
issues.
AB - Over the years, connection websites and speed dating events have increasingly
attracted singles and couples who cannot have a child in the 'traditional' way.
These initiatives bring together candidate gamete providers and recipients with
the promise of offering more freedom of choice than fertility centres or sperm
banks currently do. Depending on the level of contact desired, the role of the
gamete provider may range from not being involved at all to sharing full parental
rights and obligations. In this paper, we take a look at the ethical and social
issues that emerge with these new forms of family arrangements. We suggest that,
although the private arrangements promote greater autonomy and control for all
parties involved, risks and questionable assumptions are also at play. In
particular, risks involve insufficient screening of the involved donor or co
parent, particularly in terms of motives and psychological characteristics. One
must also be wary of the risk of unregulated commercialization and, more
importantly, of disappointments and legal conflicts caused by unclear or changing
expectations. We also warn for the risk of reinforcing heterosexist and genetic
norms of parenting and valid family building.
PMID- 27502068
TI - Anti-Mullerian hormone for prediction of ovarian response in Chinese infertile
women undergoing IVF/ICSI cycles: a prospective, multi-centre, observational
study.
AB - This study explored the correlation between serum anti-Mullerian hormone (AMH)
concentration and the number of retrieved oocytes after ovarian stimulation in
Chinese infertile women undergoing assisted reproductive technology treatment and
AMH cut-off values predicting low and high ovarian response. This was a
prospective, multi-centre, observational study. A total of 615 subjects were
included in nine assisted reproductive centres in China for outcome analysis.
Subjects received assisted reproductive technology treatment and used recombinant
human FSH (r-HFSH) or r-HFSH plus recombinant LH (rLH) for ovarian stimulation
according to conventional treatment regimens. The main outcome variables were
correlations between AMH and the number of retrieved oocytes and the cut-off
values of AMH predicting low and high ovarian response. Serum AMH concentration
was positively correlated with the number of oocytes retrieved in Chinese
infertile women treated with IVF/intracytoplasmic sperm injection (ICSI) (Pearson
correlation coefficient = 0.4754, P < 0.0001). The optimal AMH cut-off value was
2.6 ng/ml (sensitivity: 81.28%, specificity: 59.51%) in predicting high and
normal response, and 1.1 ng/ml (sensitivity: 52.27%, specificity: 87.23%) in
predicting low and normal response. In conclusion, serum AMH concentration can be
used as a biomarker to predict ovarian response in Chinese infertile women
treated with assisted reproductive technology.
PMID- 27502070
TI - Erratum to: The anti-tumor effect of the quinoline-3-carboxamide tasquinimod:
blockade of recruitment of CD11b+ Ly6Chi cells to tumor tissue reduces tumor
growth.
PMID- 27502071
TI - Perceived discrimination and self-rated health in Canada: an exploratory study.
AB - BACKGROUND: Our objective was to explore whether the link between discrimination
and self-rated health status differed as a function of discrimination type,
including discrimination based on ethnicity/culture, race, physical appearance
(other than skin colour), religion, age, and disability. METHODS: A sample of
19,422 men and women aged 15 and older was included in this study. A multivariate
logistic regression analysis was used to measure the association between
perceived discrimination types and self-reported health status defined as
excellent/good versus fair/poor. RESULTS: The prevalence of experiencing any
discrimination in the past five years was higher among those who rated their
health as fair or poor (21.8 %) compared to those who rated their health as
excellent or good (14.5 %, p < 0.0001). After controlling for all other
covariates, there was a positive association between poorer self-rated health and
two of the six specific discrimination variables entered into the model:
perceived discrimination based on physical appearance (other than skin colour)
(OR = 1.79, 95 % CI: 1.24, 2.58) and perceived discrimination based on a having a
disability (OR = 1.59, 95 % CI: 1.04, 2.41). CONCLUSIONS: Our main findings
indicate that perceived discrimination based on physical appearance and
disability may have an adverse impact on health. The results highlight the need
for a comprehensive approach to improving health outcomes that should include
policies that are targeted against specific types of discrimination.
PMID- 27502069
TI - EGFR and SYNE2 are associated with p21 expression and SYNE2 variants predict post
operative clinical outcomes in HBV-related hepatocellular carcinoma.
AB - This study was to explore the association between gene variants and p21
expression and investigate the TP53-independent p21 regulation in hepatitis B
virus (HBV) related hepatocellular carcinoma (HCC) patients from Guangxi by
genome-wide association study. 426 HBV-related HCC patients were enrolled.
Results showed that, after quality control, a total of 21,643 SNPs were
identified in 107 p21 positive and 298 p21 negative patients. The variants of
epidermal growth factor receptor (EGFR; rs2227983 and rs6950826) and spectrin
repeat containing, nuclear envelope 2 (SYNE2; rs8010699, rs4027405 and rs1890908)
were associated with p21 expression. Moreover the haplotype block (rs2227983 and
rs6950826, r(2) = 0.378) in EGFR and the haplotype block in SYNE2 (rs8010699 was
in strong LD with rs4027405 and rs1890908 (r(2) = 0.91 and 0.70, respectively))
were identified, and the haplotype A-G of EGFR and haplotype G-A-A of SYNE2 were
significantly associated with p21 expression (P < 0.01). rs4027405 and rs1890908
were significantly associated with overall survival, and patients with AG/GG
genotypes of SYNE2 gene had a worse overall survival (P = 0.001, P = 0.002). Our
findings indicate that variants of EGFR and SYNE2 play an important role in p21
regulation and are associated with the clinical outcome of HBV-related HCC in a
TP53-indenpdent manner.
PMID- 27502072
TI - Outcome and late effects among acute myeloid leukemia survivors: a nationwide
population-based study.
AB - BACKGROUND: Understanding of pathogenesis and treatment for acute myeloid
leukemia (AML) is growing. However, studies regarding the outcomes and late
effects among AML survivors are relatively limited. METHODS: This nationwide
population-based study used medical records from the Taiwanese National Health
Insurance Research Database. A total of 3356 AML patients diagnosed from 2000 to
2008 were analyzed. The physiological and psychological morbidities in AML
survivors were compared to those identified from a normal population. This study
also compared late effects among AML survivors treated by intensive chemotherapy
alone and allogeneic hematopoietic stem cell transplantation (allo-HSCT).
RESULTS: The incidence of AML in Taiwan has increased from 1.07 per 100,000
persons in 2000 to 2.17 per 100,000 persons in 2008 (p < 0.0001). With the median
overall survival (OS) time of 0.98 years, 25.0 % of AML patients in this study
cohort received best supportive care alone. Compared to the normal population,
AML survivors had higher rates of hypertension (hazard ratio [HR] 1.69; 95 %
confidence interval [CI] 1.18-2.42; p < 0.01), cardiovascular disease (HR 2.53;
95 % CI 1.39-4.61; p < 0.01), diabetes (HR 2.27; 95 % CI 1.48-3.48; p < 0.001),
and psychological disorders (HR 1.45; 95 % CI 1.04-2.04; p < 0.05). Although
patients undergoing allo-HSCT had a better OS than did patients treated with
intensive chemotherapy alone (median not reached vs. 1.53 years; p < 0.0001),
diabetes was found more often among allo-HSCT recipients than among patients
receiving intensive chemotherapy only (HR 2.93; 95 % CI 1.21-7.08; p < 0.05).
CONCLUSION: Regular physical and psychological surveillance of AML survivors is
needed especially for those receiving allo-HSCT.
PMID- 27502075
TI - Dermoscopic findings in pigmented Bowen's disease of the lip.
PMID- 27502074
TI - Fabrication of Unique Magnetic Bionanocomposite for Highly Efficient Removal of
Hexavalent Chromium from Water.
AB - Biotreatment of hexavalent chromium has attracted widespread interest due to its
cost effective and environmental friendliness. However, the difficult separation
of biomass from aqueous solution and the slow hexavalent chromium bioreduction
rate are bottlenecks for biotechnology application. In this approach, a core
shell structured functional polymer coated magnetic nanocomposite was prepared
for enriching the hexavalent chromium. Then the nanocomposite was connected to
the bacteria via amines on bacterial (Bacillus subtilis ATCC-6633) surface. Under
optimal conditions, a series of experiments were launched to degrade hexavalent
chromium from the aqueous solution using the as-prepared bionanocomposite.
Results showed that B. subtilis@Fe3O4@mSiO2@MANHE (BFSM) can degrade hexavalent
chromium from the water more effectively (a respectable degradation efficiency of
about 94%) when compared with pristine B. subtilis and Fe3O4@mSiO2@MANHE (FSM).
Moreover, the BFSM could be separated from the wastewater by magnetic separation
technology conveniently due to the Fe3O4 core of FSM. These results indicate that
the application of BFSM is a promising strategy for effective treating wastewater
containing hexavalent chromium.
PMID- 27502073
TI - Extending the Minority Stress Model to Incorporate HIV-Positive Gay and Bisexual
Men's Experiences: a Longitudinal Examination of Mental Health and Sexual Risk
Behavior.
AB - BACKGROUND: Minority stress theory represents the most plausible conceptual
framework for explaining health disparities for gay and bisexual men (GBM).
However, little focus has been given to including the unique stressors
experienced by HIV-positive GBM. PURPOSE: We explored the role of HIV-related
stress within a minority stress model of mental health and condomless anal sex.
METHODS: Longitudinal data were collected on a diverse convenience sample of 138
highly sexually active, HIV-positive GBM in NYC regarding sexual minority
(internalized homonegativity and gay-related rejection sensitivity) and HIV
related stressors (internalized HIV stigma and HIV-related rejection
sensitivity), emotion dysregulation, mental health (symptoms of depression,
anxiety, sexual compulsivity, and hypersexuality), and sexual behavior
(condomless anal sex with all male partners and with serodiscordant male
partners). RESULTS: Across both sexual minority and HIV-related stressors,
internalized stigma was significantly associated with mental health and sexual
behavior outcomes while rejection sensitivity was not. Moreover, path analyses
revealed that emotion dysregulation mediated the influence of both forms of
internalized stigma on symptoms of depression/anxiety and sexual
compulsivity/hypersexuality as well as serodiscordant condomless anal sex.
CONCLUSIONS: We identified two targets of behavioral interventions that may lead
to improvements in mental health and reductions in sexual transmission risk
behaviors-maladaptive cognitions underlying negative self-schemas and
difficulties with emotion regulation. Techniques for cognitive restructuring and
emotion regulation may be particularly useful in the development of interventions
that are sensitive to the needs of this population while also highlighting the
important role that structural interventions can have in preventing these
disparities for future generations.
PMID- 27502076
TI - Cell-based phenotypic screening of mast cell degranulation unveils kinetic
perturbations of agents targeting phosphorylation.
AB - Mast cells play an essential role in initiating allergic diseases. The activation
of mast cells are controlled by a complicated signal network of reversible
phosphorylation, and finding the key regulators involved in this network has been
the focus of the pharmaceutical industry. In this work, we used a method named
Time-dependent cell responding profile (TCRP) to track the process of mast cell
degranulation under various perturbations caused by agents targeting
phosphorylation. To test the feasibility of this high-throughput cell-based
phenotypic screening method, a variety of biological techniques were used. We
further screened 145 inhibitors and clustered them based on the similarities of
their TCRPs. Stat3 phosphorylation has been widely reported as a key step in mast
cell degranulation. Interestingly, our TCRP results showed that a Stat3 inhibitor
JSI124 did not inhibit degranulation like other Stat3 inhibitors, such as
Stattic, clearly inhibited degranulation. Regular endpoint assays demonstrated
that the distinctive TCRP of JSI124 potentially correlated with the ability to
induce apoptosis. Consequently, different agents possibly have disparate
functions, which can be conveniently detected by TCRP. From this perspective, our
TCRP screening method is reliable and sensitive when it comes to discovering and
selecting novel compounds for new drug developments.
PMID- 27502077
TI - Correction: Selective and broad spectrum amphiphilic small molecules to combat
bacterial resistance and eradicate biofilms.
AB - Correction for 'Selective and broad spectrum amphiphilic small molecules to
combat bacterial resistance and eradicate biofilms' by Jiaul Hoque et al., Chem.
Commun., 2015, 51, 13670-13673.
PMID- 27502078
TI - Acute myocardial infarction.
AB - Acute myocardial infarction has traditionally been divided into ST elevation or
non-ST elevation myocardial infarction; however, therapies are similar between
the two, and the overall management of acute myocardial infarction can be
reviewed for simplicity. Acute myocardial infarction remains a leading cause of
morbidity and mortality worldwide, despite substantial improvements in prognosis
over the past decade. The progress is a result of several major trends, including
improvements in risk stratification, more widespread use of an invasive strategy,
implementation of care delivery systems prioritising immediate revascularisation
through percutaneous coronary intervention (or fibrinolysis), advances in
antiplatelet agents and anticoagulants, and greater use of secondary prevention
strategies such as statins. This seminar discusses the important topics of the
pathophysiology, epidemiological trends, and modern management of acute
myocardial infarction, focusing on the recent advances in reperfusion strategies
and pharmacological treatment approaches.
PMID- 27502079
TI - Synthesis, Characterization, and Microwave Absorption Property of the
SnO2Nanowire/Paraffin Composites.
AB - In this article, SnO2nanowires (NWs) have been prepared and their microwave
absorption properties have been investigated in detail. Complex permittivity and
permeability of the SnO2NWs/paraffin composites have been measured in a frequency
range of 0.1-18 GHz, and the measured results are compared with that calculated
from effective medium theory. The value of maximum reflection loss for the
composites with 20 vol.% SnO2NWs is approximately -32.5 dB at 14 GHz with a
thickness of 5.0 mm.
PMID- 27502080
TI - Validity of body adiposity index in predicting body fat in Brazilians adults.
AB - OBJECTIVES: The aim of this study was to compare various methods of assessing
body compositions with body adiposity index (BAI) and to identify the validity of
BAI as a predictor of body fat in Brazilian adults. METHODS: This study included
706 individuals (average age 37.3 years, SD = 12.1). Anthropometric data included
percent body fat obtained by skinfold thicknesses, bioelectrical impedance
analysis and DXA. Body mass index (BMI), waist/hip ratio, and BAI were
calculated. The correlation between variables was assessed by Pearson's
correlation coefficient, and the Bland-Altman and Kaplan Meier graphic approaches
were used to verify the agreement between BAI and DXA. RESULTS: There was a
strong correlation between BAI and BMI (r = 0.84 in men and r = 0.86 in women, P
< .001), waist circumference (r = 0.77 in men and r = 0.75 in women, P < .001)
percent fat by skinfold thicknesses (r = 0.71 in men and r = 0.71 in women, P <
.001) and by DXA (r = 0.72 in men and r = 0.78 in women, P < .001). The Bland
Altman approach showed an overestimation of BAI in males and an underestimation
in women using DXA as the reference method. The agreement between BAI and DXA
through the Kaplan-Meier analysis was 41%. CONCLUSIONS: It was found that BAI
does not replace other measurements of body fat, but compared with more complex
methods can be an alternative for estimating the body fat in the absence of these
methods.
PMID- 27502081
TI - Highly Efficient Interfaces in Nanocomposites Based on Polyethylene and ZnO
Nano/Hierarchical Particles: A Novel Approach toward Ultralow Electrical
Conductivity Insulations.
AB - Polyethylene nanocomposites based on functionalized ZnO nano/hierarchical
particles with highly effective interfacial surface area are presented, for the
next generation of ultralow transmission-loss high-voltage DC insulating
materials.
PMID- 27502082
TI - Relationship between type 1 metabotropic glutamate receptors and cerebellar
ataxia.
AB - Imaging of type 1 metabotropic glutamate receptor (mGluR1) has recently become
possible using positron emission tomography (PET). We aimed to examine the
relationship between mGluR1 and cerebellar ataxia. Families with spinocerebellar
ataxia type 19/22 (SCA19/22) and SCA6, six patients with sporadic SCA, and 26
healthy subjects underwent PET using an mGluR1 radiotracer. Volumes-of-interest
were placed on the anterior and posterior lobes and vermis. The binding potential
(BPND) was calculated to estimate mGluR1 availability. A partial volume
correction was applied to the BPND values. The Scale for the Assessment and
Rating of Ataxia (SARA) score were measured. In each patient with SCA19/22 and
SCA6, the anterior lobe showed the highest decrease rates in the BPND values,
compared with healthy subjects. In the families with SCA19/22 and SCA6, the
disease durations and SARA scores were shorter and lower, respectively, in the
offspring, compared with the parents. However, the offspring paradoxically showed
lower BPND values, especially in the anterior lobe, compared with the parents.
The patients with sporadic SCA showed significantly lower BPND values in all
subregions than healthy subjects. The BPND values significantly correlated with
the SARA scores in all participants. In conclusion, these results showed a
decrease in mGluR1 availability in patients with hereditary and sporadic SCA, a
correlation between mGluR1 availability and degree of cerebellar ataxia, and
paradoxical findings in two families. These results suggest the potential use of
mGluR1 imaging as a specific biomarker of cerebellar ataxia.
PMID- 27502083
TI - A novel mutation m.8561C>G in MT-ATP6/8 causing a mitochondrial syndrome with
ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic
hypogonadism.
AB - Defects in the respiratory chain or mitochondrial ATP synthase (complex V) result
in mitochondrial dysfunction that is an important cause of inherited neurological
disease. Two of the subunits of complex V are encoded by MT-ATP6 and MT-ATP8 in
the mitochondrial genome. Pathogenic mutations in MT-ATP6 are associated with the
Leigh syndrome, the syndrome of neuropathy, ataxia, and retinitis pigmentosa
(NARP), as well as with non-classical phenotypes, while MT-ATP8 is less
frequently mutated in patients with mitochondrial disease. We investigated two
adult siblings presenting with features of cerebellar ataxia, peripheral
neuropathy, diabetes mellitus, sensorineural hearing impairment, and
hypergonadotropic hypogonadism. As the phenotype was suggestive of mitochondrial
disease, mitochondrial DNA was sequenced and a novel heteroplasmic mutation
m.8561C>G in the overlapping region of the MT-ATP6 and MT-ATP8 was found. The
mutation changed amino acids in both subunits. Mutation heteroplasmy correlated
with the disease phenotype in five family members. An additional assembly
intermediate of complex V and increased amount of subcomplex F1 were observed in
myoblasts of the two patients, but the total amount of complex V was unaffected.
Furthermore, intracellular ATP concentration was lower in patient myoblasts
indicating defective energy production. We suggest that the m.8561C>G mutation in
MT-ATP6/8 is pathogenic, leads biochemically to impaired assembly and decreased
ATP production of complex V, and results clinically in a phenotype with the core
features of cerebellar ataxia, peripheral neuropathy, diabetes mellitus, and
hypergonadotropic hypogonadism.
PMID- 27502084
TI - Sir William Withey Gull (1816-1890).
PMID- 27502085
TI - Diagnostic accuracy of nerve ultrasound in hereditary and sporadic non-entrapment
neuropathies.
AB - The objective of this study is to compare the diagnostic accuracy of nerve
ultrasound (US) and nerve conduction studies (NCS) for acquired non-entrapment
peripheral neuropathies (PNP) and hereditary motor and sensory neuropathies
(HMSN) in a routine clinical setting. The methods are based on a single-center,
prospective, examiner-blinded cross-sectional study on three subject groups of
healthy controls, PNP (both enrolled by a consecutive recruitment strategy), and
HMSN patients (convenience sample). A clinical reference standard based on the
neuropathy impairment (NIS) and neuropathy symptoms scores (NSS) was used for PNP
as the external validation criterion. Diagnostic accuracy was assessed by
receiver-operating curve (ROC) analyses of single-nerve measurements and logit
models. Of a total of 676 consecutively screened subjects, 107 (15.8 %) were
recruited, of which 36 (33.6 %) had a PNP. HMSN group consisted of 53 subjects
(30 subjects (56.6 %) with genetic confirmation). AUCs of best diagnostic logit
models to distinguish between controls and PNP patients were 0.86 for US and 0.97
for NCS corresponding to an equivalent specificity [US 93 % (95 % CI: 83-98 %),
NCS 89 % (95 % CI: 78-95 %)], but inferior sensitivity of US [US 56 % (95 % CI:
35-74 %), NCS 97 % (95 % CI: 84-100 %)]. For differentiation between PNP and
HMSN, both methods had equivalent AUCs of 0.95 corresponding to similar
sensitivities/specificities. Simpler diagnostic models based on measurement
protocols feasible for clinical routine revealed similar diagnostic accuracies.
US has an inferior sensitivity than NCS for acquired PNP, but comparable
specificity. For identification of HMSN in a PNP population, US and NCS show
comparable performance.
PMID- 27502086
TI - Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite
subpopulation.
AB - Spinocerebellar ataxia type 3 is an autosomal dominant ataxia with various
phenotypes affecting Jews of Yemenite origin in Israel. Clinical and family
pedigrees data of 125 Yemenite Jewish patients were collected in our clinic. All
examined patients underwent a detailed neurological and bedside vestibular
examination. Cytosine-adenine-guanine repeats size in the Ataxin-3 gene was
measured, and patients with expanded cytosine-adenine-guanine repeats >44 were
diagnosed genetically as having spinocerebellar ataxia type 3. We estimated a
disease prevalence rate of about 29/100,000 in Jew of Yemenite descendents living
in Israel. We were able to group patients into 17 families. Mean age of onset was
44 years. 74 % of our population expressed neurological signs compatible with sub
phenotype III, i.e., ataxia and polyneuropathy. Vestibulo-ocular reflex deficit
detected on bedside examination was found in 90 % of the patients. The mean
number of cytosine-adenine-guanine repeats in the Ataxin-3 gene of the diseased
allele was 67 (range 55-76). Age of onset was inversely correlated with the
number of cytosine-adenine-guanine repeats (r = -0.7) and was significantly
earlier among male patients. Though the mean number of cytosine-adenine-guanine
repeats was not larger in the offspring, their age of onset was significantly
earlier than that of their parents. In addition, paternal offspring expressed the
disease significantly earlier than maternal offspring. Signs and stages of
disease seem to progress slower during the first 10-15 years of the disease and
faster afterward. A high disease prevalence rate in our Yemenite Jewish
subpopulation is similar to that found in other isolated populations in other
countries. Vestibulo-ocular reflex deficit detected on bedside examination should
be added as part of the phenotype of Yemenite Jewish patients. Our clinical and
genetic findings are in partial agreement with other spinocerebellar ataxia type
3 population studies and are relevant to patient management and the design of
further studies.
PMID- 27502087
TI - Bilateral nevus comedonicus of the eyelids associated with bladder cancer and
successful treatment with topical tretinoin.
PMID- 27502088
TI - Influence of alterations in heart rate on left ventricular echocardiographic
measurements in healthy cats.
AB - Objectives The purpose of this study was to evaluate the effect of sudden
alterations in heart rate (HR) on left ventricular (LV) wall thickness and
dimensions determined by echocardiography in healthy cats. Methods Six
experimental cats were used. All cats were anaesthetised and HR was controlled
with right atrial pacing. The interventricular septum and left ventricular free
wall thickness at end diastole (IVSd and LVFWd, respectively), left ventricular
end-diastolic and end-systolic diameter (LVIDd and LVIDs, respectively) and
shortening fraction (FS) of each cat were assessed using echocardiography at
pacing rates of 120, 130, 140, 150, 160, 170 and 180 ppm. Results There were
significant relationships between HR and IVSd, LVFWd, LVIDd, LVIDs and FS. As the
HR increased, LV wall thickness increased and chamber dimensions got smaller in a
linear fashion. The maximum and minimum differences in wall thickness between 120
ppm and 180 ppm were 2.0 mm and 0.7 mm in single measurements, respectively.
Conclusions and relevance LV wall thickness and dimensions were significantly
influenced by alterations in HR.
PMID- 27502089
TI - Molecular characterisation of parvoviruses from domestic cats reveals emergence
of newer variants in India.
AB - Objectives The present study was undertaken to characterise the viral polypeptide
2 (VP2) gene of parvovirus from domestic cats in India. Methods The faecal
samples from diarrhoeic/healthy domestic cats were collected from different
geographical regions of India for screening by PCR assay followed by sequence
analysis of the VP2 gene. Results Canine parvovirus (CPV)/feline panleukopenia
virus (FPV) infections were found in 12 (11.3%) of 106 faecal samples tested. Two
new CPV-2a (297Ala and Asn426) and three FPV strains were identified by VP2 gene
analysis. Several unique and existing amino acid mutations were found, suggesting
continuous evolution and emergence of newer variants. The phylogenetic analysis
of the CPV sequences revealed that the two new CPV-2a strains from Mumbai (MC8)
and Puducherry (P15) were clustered together in a single clade but had evolved
independently and were ancestrally related to Chinese CPV-2a isolates. The FPV
sequences (T-C-6 and T-C-1) from Thrissur, Kerala, formed a different clade (FPV
clade) and were closely related to each other and had an ancestral relationship
with an FPV isolate from the USA. Another FPV isolate from Goa (GC1) was
positioned in the same clade but had evolved independently. Conclusions and
relevance Detection of CPV in both diarrhoeic/healthy cats and the occurrence of
FPV infection in a vaccinated cat provide new insights into parvovirus infections
in cats in India.
PMID- 27502090
TI - Full-Term Small-for-Gestational-Age Newborns in the U.S.: Characteristics,
Trends, and Morbidity.
AB - Objectives The magnitude, characteristics, and morbidity of term (>=37 weeks
gestation) newborns that are small-for-gestational-age (SGA) in the U.S. are
underexplored. We sought to examine characteristics and trends for SGA-coded term
newborns in the U.S. Methods Data were obtained from the Nationwide Inpatient
Sample, a nationally representative database of hospital stays in the U.S. from
2002 to 2011. Term, singleton newborns with SGA codes were identified and
examined over the study period. Demographic characteristics were compared for
term newborns according to presence of SGA codes using chi2 tests. Odds ratios
(OR) were calculated to compare morbidities between the two groups, adjusting for
relevant demographic and clinical variables. Results In 2011, 15 per 1000 term
newborns in the U.S. were coded as SGA, a 29.9 % increase since 2002. Compared
with other term newborns, SGA term newborns were significantly (p < 0.05) more
likely to be female, receive public insurance, and reside in lower income zip
codes. Comorbidities, including perinatal complications, metabolic disorders,
central nervous system diseases, infection, and neonatal abstinence syndrome were
more common among SGA-coded term newborns. These newborns also had higher odds of
in-hospital death (OR = 3.0 95 % confidence interval: 2.0, 4.4), longer mean
length of stay (3.7 vs. 2.3 days, p < 0.001), and higher mean hospital charges
($12,621 vs. $5012, p < 0.001). Conclusions for practice Term newborns coded as
SGA have higher morbidity, mortality, and incur higher hospital charges than
other term newborns. More research is needed to understand causes of SGA so its
incidence and effects can be reduced.
PMID- 27502091
TI - Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and
Clinical Advances.
AB - While the majority of children and adolescents with newly diagnosed childhood
acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients
will experience relapse. On current treatment regimens, the intensity of upfront
treatment is stratified based upon prognostic factors with the aim of improving
cure rates (for those at the highest risk of relapse) and minimizing treatment
related morbidity (for lower-risk patients). Here we review advances in the
understanding of prognostic factors and their application. We also highlight
novel treatment approaches aimed at improving outcomes in childhood ALL.
PMID- 27502093
TI - Editors' Notes.
PMID- 27502094
TI - Setting the Stage: The Intersection of Leadership and Assessment.
AB - This chapter provides an overview of leadership and assessment and addresses the
complexity of assessing leadership.
PMID- 27502092
TI - Improving Prognostic Modeling in Myelodysplastic Syndromes.
AB - Myelodysplastic syndromes (MDSs) are a heterogeneous group of disorders
characterized by the accumulation of complex genetic alterations that drive
disease pathogenesis and outcome. Several prognostic models have been developed
over the last two decades to risk stratify patients with MDS. These models mainly
used clinical variables including blast percentage, cytopenias, cytogenetics,
transfusion dependency, and age. Recently, somatic mutations in specific genes
have been shown to impact overall survival in MDS and can be incorporated into
established prognostic models to improve their predictive abilities. Here, we
review the advantages and disadvantages of established prognostic models in MDS
and the impact of emerging data regarding the incorporation of somatic mutations
in risk stratification.
PMID- 27502095
TI - Developing a Comprehensive Assessment Plan.
AB - This chapter provides practical advice for developing a comprehensive assessment
plan. Two examples from institutions that have created both individual and
program-level assessment plans for leadership programs are shared.
PMID- 27502096
TI - Exploring the Language of Leadership Learning and Education.
AB - This chapter examines the importance of language in the emerging field of
leadership, especially when establishing and maintaining partnerships and when
designing pedagogical practices for leadership learning.
PMID- 27502097
TI - Assessing Student Leadership Competency Development.
AB - Many mission statements include language focusing on the institutional commitment
to develop student leaders who will affect their communities and professions upon
graduation. This chapter explores how institutions can ensure that elements of
the experience are factors in a student's leadership development.
PMID- 27502098
TI - Assessing Leadership Using National Assessment Tools.
AB - Determining the appropriate use of national or multicampus leadership assessments
requires careful consideration of program goals and resources. This chapter
explores quantitative dimensions of assessing leadership.
PMID- 27502099
TI - Carts Before Horses? Remembering the Primacy of the Student's Experience in
Student Learning.
AB - This chapter makes a case for employing qualitative methodologies in the
assessment of student leadership programs. Frameworks for reflective practice are
discussed.
PMID- 27502100
TI - Leadership Assessment from an Institutional Approach.
AB - This chapter provides information about linking undergraduates' leadership
development assessment to institutional student learning outcomes illustrated by
a case example at the University of Minnesota.
PMID- 27502102
TI - [Not Available].
PMID- 27502101
TI - Breast pumps as an incentive for breastfeeding: a mixed methods study of
acceptability.
AB - Increasing breastfeeding rates would improve maternal and child health, but
multiple barriers to breastfeeding persist. Breast pump provision has been used
as an incentive for breastfeeding, although effectiveness is unclear. Women's use
of breast pumps is increasing and a high proportion of mothers express
breastmilk. No research has yet reported women's and health professionals'
perspectives on breast pumps as an incentive for breastfeeding. In the Benefits
of Incentives for Breastfeeding and Smoking cessation in pregnancy (BIBS) study,
mixed methods research explored women's and professionals' views of breast pumps
as an incentive for breastfeeding. A survey of health professionals across
Scotland and North West England measured agreement with 'a breast pump costing
around L40 provided for free on the NHS' as an incentive strategy. Qualitative
interviews and focus groups were conducted in two UK regions with a total of 68
participants (pregnant women, new mothers, and their significant others and
health professionals) and thematic analysis undertaken. The survey of 497 health
professionals found net agreement of 67.8% (337/497) with the breast pump
incentive strategy, with no predictors of agreement shown by a multiple ordered
logistic regression model. Qualitative research found interrelated themes of the
'appeal and value of breast pumps', 'sharing the load', 'perceived benefits',
'perceived risks' and issues related to 'timing'. Qualitative participants
expressed mixed views on the acceptability of breast pumps as an incentive for
breastfeeding. Understanding the mechanisms of action for pump type, timing and
additional support required for effectiveness is required to underpin trials of
breast pump provision as an incentive for improving breastfeeding outcomes. (c)
2016 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.
PMID- 27502103
TI - Bosentan as Adjunctive Therapy for Persistent Pulmonary Hypertension of the
Newborn: Results of the Randomized Multicenter Placebo-Controlled Exploratory
Trial.
AB - OBJECTIVE: To evaluate the efficacy, safety, and pharmacokinetics of the
endothelin receptor antagonist bosentan as adjunctive therapy for neonates with
persistent pulmonary hypertension of the newborn (PPHN). STUDY DESIGN: This was a
phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE
4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled
nitric oxide (iNO) treatment (>=4 hours), and had persistent respiratory failure
(oxygenation index [OI] >=12). After 2:1 randomization, bosentan 2 mg/kg or
placebo was given by nasogastric tube twice daily for >=48 hours and up to 1 day
after iNO weaning. RESULTS: Twenty-one neonates received a study drug (13
bosentan, 8 placebo). Compared with the placebo group, the group treated with
bosentan had a higher median baseline OI and greater need for vasoactive agents.
One treatment failure (need for extracorporeal membrane oxygenation) occurred in
the group treated with bosentan. The time to weaning from iNO or mechanical
ventilation was not different between the groups. Bosentan was well tolerated and
did not adversely affect systemic blood pressure or hepatic transaminase levels.
Anemia and edema were more frequent in patients receiving bosentan. Blood
concentrations of bosentan were low and variable on day 1, and achieved steady
state on day 5. CONCLUSION: Adjunctive bosentan was well tolerated, but did not
improve oxygenation or other outcomes in our patients with PPHN. This effect may
be related to delayed absorption of bosentan on treatment initiation in
critically ill neonates or to more severe illness of the neonates who received
bosentan. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01389856.
PMID- 27502104
TI - Clinical Presentation of Pediatric Patients at Risk for Sudden Cardiac Arrest.
AB - OBJECTIVES: To identify the clinical presentation of children and adolescents
affected by 1 of 4 cardiac conditions predisposing to sudden cardiac arrest:
hypertrophic cardiomyopathy, long QT syndrome (LQTS), catecholaminergic
polymorphic ventricular tachycardia (CPVT), and anomalous origin of the left
coronary artery from the right sinus of Valsalva (ALCA-R). STUDY DESIGN: This was
a retrospective review of newly diagnosed pediatric patients with hypertrophic
cardiomyopathy, LQTS, CPVT, and ALCA-R referred for cardiac evaluation at 6 US
centers from 2008 to 2014. RESULTS: A total of 450 patients (257 male/193 female;
median age 10.1 years [3.6-13.8 years, 25th-75th percentiles]) were enrolled.
Patient age was <=13 years for 70.4% of the cohort (n = 317). Sudden cardiac
arrest was the initial presentation in 7%; others were referred on the basis of
abnormal or suspicious family history, personal symptoms, or physical findings.
Patients with LQTS and hypertrophic cardiomyopathy were referred most commonly
because of family history concerns. ALCA-R was most likely to have abnormal signs
or symptoms (eg, exercise chest pain, syncope, or sudden cardiac arrest).
Patients with CPVT had a high incidence of syncope and the greatest incidence of
sudden cardiac arrest (45%); 77% exhibited exercise syncope or sudden cardiac
arrest. This study demonstrated that suspicious or known family history plays a
role in identification of many patients ultimately affected by 1 of the 3 genetic
disorders (hypertrophic cardiomyopathy, LQTS, CPVT). CONCLUSION: Important
patient and family history and physical examination findings may allow medical
providers to identify many pediatric patients affected by 4 cardiac disorders
predisposing to sudden cardiac arrest.
PMID- 27502105
TI - Social Emotional Factors Increase Risk of Postpartum Depression in Mothers of
Preterm Infants.
AB - OBJECTIVE: To examine the association of maternal mental health, perceptions of
readiness at neonatal intensive care unit (NICU) discharge, and social risk
factors with depressive symptoms 1 month postdischarge in mothers of early (<32
weeks), moderate (32-33 weeks), and late (34-36 weeks) preterm infants. A
secondary objective was to compare depressive symptoms among mothers in all
preterm groups. STUDY DESIGN: Mothers (n = 734) of preterm infants cared for >5
days in the NICU and participating in a Transition Home Program completed the
Fragile Infant Parent Readiness Evaluation prior to discharge for perceptions of
NICU staff support, infant well-being, maternal well-being (emotional
readiness/competency), and maternal comfort (worry about infant). Mental health
history and social risk factors were obtained. At 1 month postdischarge the
Edinburgh Postnatal Depression Scale was administered. Group comparisons and
logistic regression analyses were run to predict possible depression (Edinburgh
Postnatal Depression Scale >=10). RESULTS: Mothers of early, moderate, and late
preterm infants reported similar rates of possible depression (20%, 22%, and 18%,
respectively) 1 month after NICU discharge. History of mental health disorder,
decreased perception of maternal well-being, decreased maternal comfort regarding
infant, and decreased perception of family cohesion were associated with possible
depression at 1 month postdischarge. CONCLUSIONS: Mothers with a previous mental
health disorder and experiencing negative perceptions of self and infant at NICU
discharge were at increased risk for depressive symptomatology 1 month
postdischarge regardless of infant gestational age. Comprehensive mental health
assessment prior to discharge is essential to identify women at risk and provide
appropriate referral.
PMID- 27502106
TI - Comparative analyses within Gyrodactylus (Platyhelminthes: Monogenea)
mitochondrial genomes and conserved polymerase chain reaction primers for
gyrodactylid mitochondrial DNA.
AB - In this study, we describe the complete mitochondrial genomes of Gyrodactylus
brachymystacis and Gyrodactylus parvae infecting rainbow trout (Oncorhynchus
mykiss) and the invasive topmouth gudgeon (Pseudorasbora parva), respectively.
The two circular genomes have a common genome organization found in other
Gyrodactylus species. Comparative analyses of mitochondrial genomes from six
Gyrodactylus species were carried out to determine base composition, codon usage,
transfer RNA and ribosomal RNA genes, major non-coding regions, and nucleotide
diversity within the genus. We also provide the first universal models of the
secondary structures of rrnS and rrnL for this group thereby promoting
utilization of these genetic markers. Universal primers provided herein can be
used to obtain more mitochondrial information for pathogen identification and may
reveal different levels of molecular phylogenetic inferences for this lineage.
PMID- 27502107
TI - A simultaneous assessment metric for MAb quantity and glycan quality.
AB - As a critical quality attribute, glycosylation represents an important
consideration when analyzing the success of a glycoprotein production process.
Though critical, glycosylation is not the only measure of culture success; other
factors, including culture size, maintenance, and productivity, are also
critical. A new metric was developed to address both product quality, as measured
through glycosylation, and product quantity, as measured through product
concentration. A monoclonal antibody Chinese hamster ovary cell culture model
system was used to assess this metric across various media formulations. In a
model test system, the metric discriminated that some media supplements had a net
positive impact on productivity and glycosylation, while others had a net
negative impact on productivity and glycosylation.
PMID- 27502108
TI - Role of anthropometric factors, self-perception, and diet on weight misperception
among young adolescents: a cross-sectional study.
AB - PURPOSE: Adolescence overweight and obesity have increased considerably, and the
misperception of their weight status could reduce the efficiency of intervention
programs. The aim of this study was to evaluate the prevalence rate of
misperception and to assess the relationship between weight perception and
anthropometric parameters, self-perception, physical activity, and adherence to
the Mediterranean diet. METHODS: A total of 1643 young adolescents (11-16 years
old) were surveyed in a cross-sectional investigation during two scholastic years
(period October-May of 2012-2013 and 2013-2014) in 15 secondary schools of
Sicily, southern Italy. Data on demographic information, anthropometric
characteristics (bioelectrical impedance), physical activity level, The Children
and Youth Physical Self-Perception Profile, weight perception, and dietary habits
(KIDMED) were collected. RESULTS: Misperception was found in the 27.6 % of the
young adolescents, and boys were more likely to underestimate their weight
status, while girls had a high percentage of overestimation. The strong
association with weight misperception was with socioeconomic status, waist
circumference, physical activities, and physical self-worth. Moreover, a good
adherence to the Mediterranean diet was inversely associated with both
overestimation and underestimation in both boys and girls. CONCLUSION: These
findings highlight that almost one-third of the participants had a weight
misperception that was associated with several anthropometric, social, and
lifestyle factors. Future intervention to prevent overweight and obesity should
consider not only gender-specific differences, but also parental SES, perception,
and satisfaction of body weight status.
PMID- 27502109
TI - Implementation of Methodology for Quality Improvement in Pediatric Cardiac
Catheterization: A Multi-center Initiative by the Congenital Cardiac
Catheterization Project on Outcomes-Quality Improvement (C3PO-QI).
AB - The Congenital Cardiac Catheterization Project on Outcomes (C3PO) launched in
2007 as a multi-center collaborative to establish standardized and comparable
metrics for pediatric cardiac catheterization procedures. The limitations of
larger registries at the time led to the development of the next phase in 2013,
C3PO-Quality Improvement (C3PO-QI), focusing on instituting QI initiatives within
the field. The objective of this manuscript is to provide a detailed overview of
C3PO-QI and report data on case characteristics and outcome metrics being
explored. C3PO-QI was designed to cultivate institutional collaboration during
implementation of its initiatives. A database and website were developed to
support data entry and on-demand reporting. The registry prospectively captures
pediatric cardiac catheterization data among 15 hospitals. The present study
includes case demographic data (n) and quality metric reporting by case type,
age, and radiation dose variables. This dataset includes 13,135 cases entered
into the database between 1/1/2014 and 12/31/2015. Interventional cases make up
the highest percentage by case mix distribution (48 %), and patients <1 years
make up the highest percentage by age distribution (26 %). The ratio of
diagnostic and interventional procedures performed changes by age group.
Application of QI metric shows all procedure types surpassing metric goals. Large
volume data collection, such as in C3PO-QI, allows for meaningful interpretation
of data. C3PO-QI is uniquely poised to deliver fast-paced changes in the field.
Although the project initiatives are specific to pediatric cardiac
catheterization, the implementation of the project and utilization of real-time
reporting is generalizable to other specialties and multi-center collaboratives.
PMID- 27502111
TI - Evaluation of site-specific tactics using bifenazate and Neoseiulus californicus
for management of Tetranychus urticae (Acari: Tetranychidae) in strawberries.
AB - Greenhouse and field experiments were conducted to evaluate the effectiveness of
site-specific tactics for management of the twospotted spider mite, Tetranychus
urticae Koch, a major pest of greenhouse and field-grown strawberries (Fragaria x
ananassa Duchesne). Two site-specific (spot) treatments, the miticide bifenazate
(Acramite((r))) and the predatory mite Neoseiulus californicus McGregor, were
compared with whole-plot treatments of bifenazate or N. californicus to determine
whether T. urticae could be effectively managed in field-grown strawberry using
only site-specific tactics. Additionally, the cost of site-specific tactics was
compared with whole-plot treatments to determine the economic value of using site
specific management tactics for T. urticae in strawberries. In the greenhouse,
all treatments equivalently reduced the number of T. urticae below control. In
the field during the 2011-2012 season, more T. urticae eggs and motiles were in
the whole-plot treatments of both N. californicus and bifenazate in the mid
season and late season, respectively, compared with the spot treatments. With the
exception of site-specific N. californicus during the 2011-2012 field season,
there were no differences in marketable yields between plots with site-specific
treatments and whole-plot management. An economic analysis demonstrated a
significant cost savings (75.3 %) with site-specific treatments of N.
californicus compared with whole-plot application of N. californicus. Similarly,
a 24.7 % reduction in cost was achieved in using site-specific bifenazate
compared with whole-plot application of bifenazate. The findings indicate that
site-specific treatments with N. californicus and bifenazate are competitive
alternatives to whole-field application for T. urticae management in
strawberries.
PMID- 27502110
TI - Synergistic effects of baicalein with cefotaxime against Klebsiella pneumoniae
through inhibiting CTX-M-1 gene expression.
AB - BACKGROUND: Generation of extended- spectrum beta- lactamases is one of the major
mechanisms by which clinical Klebsiella pneumoniae develop resistance to
antibiotics. Combined antibiotics prove to be a relatively effective method of
controlling such resistant strains. Some of Chinese herbal active ingredients are
known to have synergistic antibacterial effects. This study is aimed to
investigate synergistic effects of Chinese herbal active ingredients with
cefotaxime on the extended- spectrum beta- lactamase positive strains of
Klebsiella pneumoniae, and to analyze mechanism of synergistic action, providing
experimental evidence for clinical application of antimicrobial drugs. RESULTS:
For total sixteen strains including fifteen strains of cefotaxime resistant K.
pneumoniae and one extended- spectrum beta- lactamase positive standard strain,
the synergy rates of cefotaxime with baicalein, matrine, and clavulanic acid were
56.3 %, 0 %, and 100 %, respectively. The fractional inhibitory concentration
index of combined baicalein and cefotaxime was correlated with the percentage
decrease of cefotaxime MIC of all the strains (r = -0.78, p <0.01). In the group
of synergy baicalein and cefotaxime, the transcribed mRNA level of CTX-M-1 after
treatment of baicalein was decreased significantly (p <0.05). Moreover, the CTX-M
1 mRNA expression percentage inhibition (100 %, 5/5) was significantly higher
than non- synergy group (25 %, 1/4) (p <0.05). CONCLUSIONS: Our study
demonstrated that baicalein exhibited synergistic activity when combined with
cefotaxime against some of extended- spectrum beta- lactamases positive K.
pneumoniae strains by inhibiting CTX-M-1 mRNA expression. However, no direct
bactericidal or bacteriostatic activity was involved in the synergistic action.
Baicalein seems to be a promising novel effective synergistic antimicrobial
agent.
PMID- 27502112
TI - Glyphosate sub-lethal toxicity to non-target organisms occurring in Jatropha
curcas plantations in Brazil.
AB - Weed management in physic nut plantations has generally been performed by
spraying the herbicide glyphosate. However, the effects of glyphosate on non
target organisms present in the crop system are unknown. Here, we evaluated the
toxicity of glyphosate (Roundup Transorb((r))) against the pest species
Polyphagotarsonemus latus (Acari: Tarsonemidae) and Tetranychus bastosi (Acari:
Tetranychidae) which can be exposed by drift. These mites are considered pests of
the physic nut; however, they can also feed and reside on weeds associated with
the crop, serving as food sources for predatory mites. When subjected to residue
(by ingestion of sap of treated plants), and direct contact to glyphosate, P.
latus reproduction was affected but T. bastosi was affected only by the residual
effect. Although the herbicide caused a reduction in the number of eggs laid by
the females of both pest mites, it is suggested that sublethal effects of
glyphosate stimulates oviposition of P. latus and T. bastosi: both species
displayed higher reproductive rates when exposed to 0.36 kg ha(-1) of the
herbicide. We conclude that glyphosate negatively affects the arthropod
herbivores studied and we discuss possible implications on their biological
control in Jatropha curcas plantations.
PMID- 27502114
TI - Suboral fork: a newly discerned gnathosomal structure from the proboscis of
eriophyoid mites (Acari, Eriophyoidea).
AB - The infracapitulum of eriophyoid mites comprises a cone-like basal
infracapitulum, containing a pharynx, and a distal infracapitulum, forming a
proboscis ensheathing a bunch of stylets. A well-developed basal labral section
was observed in all studied specimens. A newly discerned structure, the suboral
fork, situated in the ventral part of the proboscis was discovered. It is larger
in diptilomiopids and Nalepella and notably smaller in eriophyids and phytoptids.
This structure presumably determines the site of piercing and functions in a
similar way to the pressure foot of a sewing machine which controls the movements
of a needle. In diptilomiopids the suboral fork might have an additional
function: it is a stopper which prevents the proboscis from further penetrating
into plant tissues. It is possible that the suboral fork is homologous with the
labium of early derivative acariform mites. The proboscis might be a fusion
product of the infracapitular lateral lips, malapophyses and the labium. The
proboscis serves as a feeding structure in eriophyoids; two ways of sucking plant
cell sap, depending on shapes of proboscis and labrum, are hypothesized. Further
work is needed to draw conclusions on homologies and the function of all
gnathosomal structures in eriophyoids.
PMID- 27502113
TI - Detection and localization of Solitalea-like and Cardinium bacteria in three
Acarus siro populations (Astigmata: Acaridae).
AB - Bacteria associated with mites influence their fitness, nutrition and
reproduction. Previously, we found Solitalea-like (Sphingobacteriales) and
Candidatus Cardinium (Cytophagales) bacteria in the stored product mite Acarus
siro L. by cloning and using pyrosequencing. In this study, taxon-specific
primers targeting 16S rRNA gene were used to detect and quantify the bacteria in
mites and eggs of three A. siro populations. The specific probes for fluorescent
in situ hybridization (FISH) were used to localize Solitalea-like and Cardinium
bacteria in mite bodies. The population growth as an indirect estimator of
fitness was used to describe the mite-bacteria interactions on (1) control diet;
(2) rifampicin supplemented diet; (3) tetracycline supplemented diet; (4)
rifampicin pretreated mites; (5) tetracycline pretreated mites. Solitalea-like
16S rRNA gene sequences from A. siro formed a separate cluster together with
sequences from Tyrophagus putrescentiae. qPCR analysis indicated that number of
Solitalea-like bacteria 16S rRNA gene copies was ca. 100* higher than that of
Cardinium and the numbers differed between populations. FISH analysis localized
Solitalea-like bacteria in the parenchymal tissues, mesodeum and food bolus of
larvae, nymphs and adults. Solitalea-like, but not Cardinium bacteria were
detected by taxon-specific primers in mites and eggs of all three investigated
populations. None of the antibiotic treatments eliminated Solitalea-like bacteria
in the A. siro populations tested. Rifampicin pretreatment significantly
decreased the population growth. The numbers of Solitalea-like bacteria did not
correlate with the population growth as a fitness indicator. This study
demonstrated that A. siro can host Solitalea-like bacteria either alone or
together with Cardinium. We suggest that Solitalea-like bacteria are shared by
vertical transfer in A. siro populations.
PMID- 27502115
TI - Editorial (Thematic Issue: What's Behind the Sex Gap in Cardiovascular
Mortality?).
PMID- 27502116
TI - A high titre of autoantibody at onset does not predict pancreatic beta-cell fate.
PMID- 27502117
TI - Type A personality is not associated with poor glycaemic control: Data from cross
sectional and longitudinal surveys of people with type 1 or type 2 diabetes.
PMID- 27502120
TI - Editorial note.
PMID- 27502118
TI - Aromatase inhibition remodels the clonal architecture of estrogen-receptor
positive breast cancers.
AB - Resistance to oestrogen-deprivation therapy is common in oestrogen-receptor
positive (ER+) breast cancer. To better understand the contributions of tumour
heterogeneity and evolution to resistance, here we perform comprehensive genomic
characterization of 22 primary tumours sampled before and after 4 months of
neoadjuvant aromatase inhibitor (NAI) treatment. Comparing whole-genome
sequencing of tumour/normal pairs from the two time points, with coincident
tumour RNA sequencing, reveals widespread spatial and temporal heterogeneity,
with marked remodelling of the clonal landscape in response to NAI. Two cases
have genomic evidence of two independent tumours, most obviously an ER-
'collision tumour', which was only detected after NAI treatment of baseline ER+
disease. Many mutations are newly detected or enriched post treatment, including
two ligand-binding domain mutations in ESR1. The observed clonal complexity of
the ER+ breast cancer genome suggests that precision medicine approaches based on
genomic analysis of a single specimen are likely insufficient to capture all
clinically significant information.
PMID- 27502119
TI - Study design of PANGAEA 2.0, a non-interventional study on RRMS patients to be
switched to fingolimod.
AB - BACKGROUND: The therapeutic options for patients with Multiple Sclerosis (MS)
have steadily increased due to the approval of new substances that now supplement
traditional first-line agents, demanding a paradigm shift in the assessment of
disease activity and treatment response in clinical routine. Here, we report the
study design of PANGAEA 2.0 (Post-Authorization Non-interventional GermAn
treatment benefit study of GilEnyA in MS patients), a non-interventional study in
patients with relapsing-remitting MS (RRMS) identify patients with disease
activity and monitor their disease course after treatment switch to fingolimod
(Gilenya(r)), an oral medication approved for patients with highly active RRMS.
METHOD/DESIGN: In the first phase of the PANGAEA 2.0 study the disease activity
status of patients receiving a disease-modifying therapy (DMT) is evaluated in
order to identify patients at risk of disease progression. This evaluation is
based on outcome parameters for both clinical disease activity and magnetic
resonance imaging (MRI), and subclinical measures, describing disease activity
from the physician's and the patient's perspective. In the second phase of the
study, 1500 RRMS patients identified as being non-responders and switched to
fingolimod (oral, 0.5 mg/daily) are followed-up for 3 years. Data on relapse
activity, disability progression, MRI lesions, and brain volume loss will be
assessed in accordance to 'no evidence of disease activity-4' (NEDA-4). The
modified Rio score, currently validated for the evaluation of treatment response
to interferons, will be used to evaluate the treatment response to fingolimod.
The MS management software MSDS3D will guide physicians through the complex
processes of diagnosis and treatment. A sub-study further analyzes the benefits
of a standardized quantitative evaluation of routine MRI scans by a central
reading facility. PANGAEA 2.0 is being conducted between June 2015 and December
2019 in 350 neurological practices and centers in Germany, including 100 centers
participating in the sub-study. DISCUSSION: PANGAEA 2.0 will not only evaluate
the long-term benefit of a treatment change to fingolimod but also the
applicability of new concepts of data acquisition, assessment of MS disease
activity and evaluation of treatment response for the in clinical routine. TRIAL
REGISTRATION: BfArM6532; Trial Registration Date: 20/05/2015.
PMID- 27502122
TI - Freedom from long DAPT signals the demise of the bare-metal stent.
PMID- 27502121
TI - Regional and ethnic differences among patients with heart failure in Asia: the
Asian sudden cardiac death in heart failure registry.
AB - AIMS: To characterize regional and ethnic differences in heart failure (HF)
across Asia. METHODS AND RESULTS: We prospectively studied 5276 patients with
stable HF and reduced ejection fraction (<=40%) from 11 Asian regions (China,
Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore,
Taiwan, and Thailand). Mean age was 59.6 +/- 13.1 years, 78.2% were men, and mean
body mass index was 24.9 +/- 5.1 kg/m2. Majority (64%) of patients had two or
more comorbid conditions such as hypertension (51.9%), coronary artery disease
(CAD, 50.2%), or diabetes (40.4%). The prevalence of CAD was highest in Southeast
Asians (58.8 vs. 38.2% in Northeast Asians). Compared with Chinese ethnicity,
Malays (adjusted odds ratio [OR] 1.97, 95% CI 1.63-2.38) and Indians (OR 1.44,
95% CI 1.24-1.68) had higher odds of CAD, whereas Koreans (OR 0.38, 95% CI 0.29
0.50) and Japanese (OR 0.44, 95% CI 0.36-0.55) had lower odds. The prevalence of
hypertension and diabetes was highest in Southeast Asians (64.2 and 49.3%,
respectively) and high-income regions (59.7 and 46.2%, respectively). There was
significant interaction between ethnicity and region, where the adjusted odds
were 3.95 (95% CI 2.51-6.21) for hypertension and 4.91 (95% CI 3.07-7.87) for
diabetes among Indians from high- vs. low-income regions; and 2.60 (95% CI 1.66
4.06) for hypertension and 2.62 (95% CI 1.73-3.97) for diabetes among Malays from
high- vs. low-income regions. CONCLUSIONS: These first prospective multi-national
data from Asia highlight the significant heterogeneity among Asian patients with
stable HF, and the important influence of both ethnicity and regional income
level on patient characteristics. CLINICALTRIALSGOV IDENTIFIER: NCT01633398.
PMID- 27502123
TI - Frontotemporal dementia: from molecular mechanisms to therapy.
AB - Frontotemporal dementia (FTD) is a heterogeneous clinical syndrome characterized
by frontotemporal lobar degeneration (FTLD). Neuropathologically, FTLD is
characterized by abnormal protein deposits and almost all cases can now be
classified into three major molecular subgroups based on specific accumulating
proteins with the most common being FTLD-tau and FTLD-TDP (accounting for ~40%
and 50%, respectively) and FTLD-FET (accounting for ~5-10%). In this special
issue, the molecular and genetic basics as well as clinical approaches and
therapeutics are reviewed in a series of articles. This article is part of the
Frontotemporal Dementia special issue.
PMID- 27502124
TI - Prion-like propagation as a pathogenic principle in frontotemporal dementia.
AB - Frontotemporal dementia is a devastating neurodegenerative disease causing stark
alterations in personality and language. Characterized by severe atrophy of the
frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme
heterogeneity in clinical presentation, genetic causes, and pathological
findings. Like most neurodegenerative diseases, the initial symptoms of FTD are
subtle, but increase in severity over time, as the disease progresses. Clinical
progression is paralleled by exacerbation of pathological findings and the
involvement of broader brain regions, which currently lack mechanistic
explanation. Yet, a flurry of studies indicate that protein aggregates
accumulating in neurodegenerative diseases can act as propagating entities,
amplifying their pathogenic conformation, in a way similar to infectious prions.
In this prion-centric view, FTD can be divided into three subtypes, TDP-43 or FUS
proteinopathy and tauopathy. Here, we review the current evidence that FTD-linked
pathology propagates in a prion-like manner and discuss the implications of these
findings for disease progression and heterogeneity. Frontotemporal dementia (FTD)
is a progressive neurodegenerative disease causing severe personality
dysfunctions, characterized by profound heterogeneity. Accumulation of tau, TDP
43 or FUS cytoplasmic aggregates characterize molecularly distinct and non
overlapping FTD subtypes. Here, we discuss the current evidence suggesting that
prion-like propagation and cell-to-cell spread of each of these cytoplasmic
aggregates may underlie disease progression and heterogeneity. This article is
part of the Frontotemporal Dementia special issue.
PMID- 27502125
TI - Advances in neuroimaging in frontotemporal dementia.
AB - Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous
neurodegenerative disorder with multiple underlying genetic and pathological
causes. Whilst initial neuroimaging studies highlighted the presence of frontal
and temporal lobe atrophy or hypometabolism as the unifying feature in patients
with FTD, more detailed studies have revealed diverse patterns across
individuals, with variable frontal or temporal predominance, differing degrees of
asymmetry, and the involvement of other cortical areas including the insula and
cingulate, as well as subcortical structures such as the basal ganglia and
thalamus. Recent advances in novel imaging modalities including diffusion tensor
imaging, resting-state functional magnetic resonance imaging and molecular
positron emission tomography imaging allow the possibility of investigating
alterations in structural and functional connectivity and the visualisation of
pathological protein deposition. This review will cover the major imaging
modalities currently used in research and clinical practice, focusing on the key
insights they have provided into FTD, including the onset and evolution of
pathological changes and also importantly their utility as biomarkers for disease
detection and staging, differential diagnosis and measurement of disease
progression. Validating neuroimaging biomarkers that are able to accomplish these
tasks will be crucial for the ultimate goal of powering upcoming clinical trials
by correctly stratifying patient enrolment and providing sensitive markers for
evaluating the effects and efficacy of disease-modifying therapies. This review
describes the key insights provided by research into the major neuroimaging
modalities currently used in research and clinical practice, including what they
tell us about the onset and evolution of FTD and how they may be used as
biomarkers for disease detection and staging, differential diagnosis and
measurement of disease progression. This article is part of the Frontotemporal
Dementia special issue.
PMID- 27502127
TI - [Future directions of cardiovascular surgery in China].
AB - The cardiovascular surgery in China has achieved great progress both on scale and
technology though development over the past thirty years. However, the technical
predominance of cardiovascular surgery in therapies for some diseases has been
weakened, along with developments of new drugs and interventional technology.
Besides, the change of doctor-patient relationship result from internet medical
information service and less attraction of cardiovascular surgery discipline to
talents bring certain challenge to the development of cardiovascular surgery.
Currently, cardiovascular surgeons should practice the "patient first" principle,
carry out individual customized treatment and precision therapy, absorb the
advantages of other subjects like intervention and imaging in order to achieve
technological breakthroughs, create new treatment technologies and models with
smaller trauma and better outcome, establish heart team to provide patient
oriented treatment. Besides, cardiovascular surgeons should improve knowledge
system by learning related technology and science, become hybrid doctors of
research. Cardiovascular surgeons should pay high attention to critical effect of
research on the disciplinary development, carry out question and demand oriented
clinical studies, change the medical practice by virtue of research achievements,
direct the treatment for cardiovascular diseases, and finally provide better
health service and rebuild the predominance of cardiovascular surgery.
PMID- 27502126
TI - Sequence capture using RAD probes clarifies phylogenetic relationships and
species boundaries in Primula sect. Auricula.
AB - Species-rich evolutionary radiations are a common feature of mountain floras
worldwide. However, the frequent lack of phylogenetic resolution in species-rich
alpine plant groups hampers progress towards clarifying the causes of
diversification in mountains. In this study, we use the largest plant group
endemic to the European Alpine system, Primula sect. Auricula, as a model system.
We employ a newly developed next-generation-sequencing protocol, involving
sequence capture with RAD probes, and map reads to the reference genome of
Primula veris to obtain DNA matrices with thousands of SNPs. We use these data
rich matrices to infer phylogenetic relationships in Primula sect. Auricula and
examine species delimitations in two taxonomically difficult subgroups: the
clades formed by the close relatives of P. auricula and P. pedemontana,
respectively. Our molecular dataset enables us to resolve most phylogenetic
relationships in the group with strong support, and in particular to infer four
well-supported clades within sect. Auricula. Our results support existing species
delimitations for P. auricula, P. lutea, and P. subpyrenaica, while they suggest
that the group formed by P. pedemontana and close relatives might need taxonomic
revision. Finally, we discuss preliminary implications of these findings on the
biogeographic history of Primula sect. Auricula.
PMID- 27502128
TI - [Standardize the endovascular treatment for arteriosclerosis obliterans].
AB - Endovascular therapy has become the first-line strategy for most peripheral
artery disease cases. Currently, many guidelines recommend endovascular therapy
as the first choice for arteriosclerosis obliterans. Recently, drug-eluting stent
and drug-coated balloon are available. The clinical outcomes have been greatly
improved with the evolution of devices. However, the long-term outcomes of
endovascular therapy for arteriosclerosis obliterans are still not satisfied.
Many centers treat arteriosclerosis obliterans using endovascular therapy in
appropriately. In this editorial, an evidence-based approach and some strategies
will be discussed to standardize the endovascular treatment and improve the
result of endovascular therapy for arteriosclerosis obliterans.
PMID- 27502129
TI - [Transcatheter aortic valve replacement: the new era, new opportunity and new
challenge of cardiac surgery].
AB - Conventional surgical aortic valve replacement is still the current "gold
standard" in treatment of aortic valve disease, but part of the high-risk elder
patients couldn't tolerate the surgical trauma. Now those people could receive
timely and effective treatment with the application of transcatheter aortic valve
replacement, and the related guidelines have been published in recent years. With
its wide use in recent 10 years, different implantation systems, such as SAPIEN,
CoreValve, Lotus, ACURATE neo, have been gradually improved and provened in
several large clinical trials. Transfemoral, transapical and transaortic
approaches are approved for the access and used according to different
indications. Bleeding, vascular events, III grade atrioventricular block,
coronary obstruction, valve malpositioning, valve degeneration are the major
complications for this skill, but would be overcome with the improvement of the
system. The transcather aortic valve replacement brings not only the opportunity
to develop new treatment protocols, but the challenge for cardiac surgeons to
learn new skills to control.
PMID- 27502130
TI - [Thought on the techniques of totally thoracoscopic cardiac surgery].
AB - Minimally invasive surgery has become the guiding principle of the entire
surgical treatment. In last 16 years, totally thoracoscopic cardiac surgery
(TTCS) has developed rapidly, and achieved good results. However, there are
obvious differences between the basic surgical techniques of TTCS and of
conventional cardiac surgery. At present, there is still lack of standard and in
sufficient evidence in the surgical techniques of TTCS. It requires professional
and standardized training and evidence-based research on TTCS, including
indication selection and procedure standardization, to improve the therapy level
of TTCS further.
PMID- 27502131
TI - [Analysis of endovascular treatment strategies on in-stent restenosis of
femoropopliteal artery lesions].
AB - Over the last few years, the treatment of complex femoropopliteal lesions led to
the increasing use of stents in this challenging anatomical area. Whereas in
stent restenosis remains the Achilles' heel of stenting this segment, and leads
to recurrent ischemia and repeated interventions. A majority of endovascular
techniques have been evaluated to repair this complication, including plain
balloon angioplasty, new stent deployment, cutting balloons but without
satisfactory mid- and long-term results. More recently debulking and drug-eluting
devices have been applied in femoropopliteal in-stent restenosis with promising
results. And relining with a stent graft or drug-eluting stent of femoropopliteal
in-stent restenosis can be considered in cases of stent fracture as this strategy
has showed relatively optimal outcomes. The aim of this article is to analyze the
evidence of those endovascular techniques for the treatment of femoropopliteal in
stent restenosis.
PMID- 27502132
TI - [Clinical experience of 2 543 cases of congenital heart diseases undergoing
totally thoracoscopic cardiac surgery in a single center].
AB - OBJECTIVE: To summarize the experience of totally thoracoscopic cardiac surgical
(TTCS) at congenital heart diseases (CHD) treatment. METHODS: From April 2000 to
March 2016, 2 543 patients with CHD underwent TTCS in Department of
Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University,
including 957 male and 1 586 female patients. The age ranged from 0.5 to 66.0
years with a mean age of (21+/-18) years. The body weight ranged from 6 to 118 kg
with a mean of (49+/-30) kg. Patients were diagnosed with echocardiography or
transesophagel echocardiography as complex or complicated CHD which was
unsuitable for percutaneous procedure. Surgical procedures were performed through
3 holes inserted at the right chest wall, and catheters were placed in the right
femoral artery and vein to set up cardiopulmonary bypass.The ascending aorta was
cross-clamped with long tailor-made forceps and the myocardium was protected by
coronary perfusion with cold crystalloid(blood)cardioplegia. There were 787 cases
(from January 2013 to December 2015) were selected to compare with 710 cases
underwent conventional thoracotomy over the same period. Statistical analysis was
performed by t test, t' test, rank-sum test, chi(2) test and Fisher exact test,
respectively. RESULTS: The total death rate and the major complication rate of
the operation were 0.35% (9/2 543) and 2.28% (58/2 543), respectively. All
patients were followed up 1 to 190 months and the average follow-up time was
(75+/-34) months. No residual shunt or obvious mitral/tricuspid regurgitation was
observed, and the patients gained better cardiac function as level I to II (New
York Heart Association classification). There was no significant difference in
aorta clamp time, ICU stay, hospital cost, and surgical fatality rate between 787
patients underwent TTCS and 710 conventional thoracotomy. The cardiopulmonary
bypass time ((31+/-20) minuets vs. (40+/-17) minuets, t'=9.407, P=0.001),
operation time ((91+/-27) minuets vs. ( 102+/-64) minuets, t'=4.251, P=0.000),
hospital stay ((5.3+/-2.2) d vs. (13.0+/-4.0) d, t'=45.463, P=0.000),
postoperative drainage (M(QR): 33(17) ml vs. 121(53) ml, T=2.632, P=0.000) and
major complications (7/787 vs. 23/710, chi(2)=10.49, P=0.001) were significantly
reduced and no sternal deformation occurrence (0 vs. 192/710, chi(2)=244.10,
P=0.000) in TTCS group. While the cost was higher in TTCS group ((24 000+/-400)
yuan vs. (20 000+/-400) yuan, t=19.320, P=0.000). CONCLUSION: TTCS is feasible,
safe, and minimal invasive for patients with CHD, resulting in quick recovery and
good median-long term outcomes.
PMID- 27502133
TI - [Transapical transcatheter aortic valve replacement for high risk elderly
patients with predominant aortic incompetence].
AB - OBJECTIVES: To introduce the application of the J-ValveTM system in elderly
patients with predominant aortic incompetence without significant valve
calcification, and to evaluate its feasibility. METHODS: From April 2014 to July
2015, 33 cases of transapical implantation of J-ValveTM were performed in
Department of Cardiac Surgery, Zhongshan Hospital, Fudan University. Sixteen of
these patients were diagnosed as predominant aortic incompetence without
significant valve calcification. There were 11 male and 5 female patients aged
from 61 to 84 years, with a mean age of (76+/-6) years. All patients had symptoms
of left ventricular dysfunction for at least 3 months. They were considered to be
prohibitive for surgical valve replacement (logistic European system for cardiac
operative risk evaluation: 22.2% to 44.4%, mean 27%+/-6% after evaluation by an
interdisciplinary heart team. The J-ValveTM system was applied in transapical
transcatheter aortic valve replacement for patients. The multi-slice CT was
performed before discharge. Clinical evaluation including patients' history,
symptoms and New York Heart Association classification and echocardiogram
evaluation were performed before discharge, 1(st) month, 3(th) month and 12(th)
month after the operation respectively. RESULTS: Implantations were successful in
all patients. One patient died from moderate paravalvular leak which led to multi
organ failure during the hospital stay. The mean time of postoperative hospital
stay of the other 15 patients was (6.1+/-1.3) days. The 15 patients were followed
by 174 to 410 days, with a median time of 188 days. Only two patients had trivial
prosthetic valve incompetence, the other 13 patients had no prosthetic valve
incompetence; two patients had no paravavular leak and the other 13 patients had
paravavular leak of no more than moderate grade. There were no major complication
or mortality during the follow-up. CONCLUSIONS: The transapical implantation of
the J-ValveTM system in high risk elderly patients with predominant aortic
incompetence is feasible.The early postoperative outcome is satisfactory.
PMID- 27502134
TI - [Comparison of anterolateral minithoracotomy versus partial upper hemisternotomy
in aortic valve replacement].
AB - OBJECTIVE: To compare the results of aortic valve replacement through
anterolateral minithoracotomy (RT) and partial upper hemisternotomy (PS)
approaches. METHODS: This was a retrospective, observational, cohort study of
collected data on 297 patients undergoing isolated primary aortic valve
replacement between July 2009 and March 2016 at Department of Cardiovascular
Surgery, Zhongshan Hospital, Fudan University. There were 174 male and 123 female
patients, aging from 15 to 73 years with a mean age of (51+/-13) years. Of these,
132 were performed through right RT and 165 through PS. Outcomes of the two
groups were compared by t test, t' test, rank-sum test and chi(2) test,
respectively. RESULTS: The overall in-hospital mortality was 1.7% (5/297), with
no difference between the 2 groups (3.0%, 4/132 vs. 0.6%, 1/165, P=0.175 ).
Patients in the RT group had longer cardiopulmonary bypass ((92+/-27) minutes vs.
(76+/-18) minutes, t'=5.848, P=0.000)and crossclamping ((56+/-21) minutes vs.
(43+/-12) minutes, t'=6.333, P=0.000)times. Three patients in the RT group and
two patients required intraoperative conversion. Patients by way of RT was
associated with a lower incidence of blood transfusions (20.4% vs. 39.4%,
chi(2)=12.303, P=0.001) and less drainage (250 (307) ml vs. 570 (370) ml,
Z=8.161, P=0.000). In addition, patients in RT group had a shorter postoperative
length of stay (5(4) days vs. 9(10) days, Z=4.548, P=0.000). CONCLUSIONS: Aortic
valve replacement via RT and PS are both safe and feasible. The approach through
PS is associated with better exposure, more extensive indication for surgery, and
more suitable to heart centers which intend to carry out miminally invasive
aortic valve replacement. While, for an experienced surgeon, the approach through
right RT is worthy of clinical selective application for patients concern more
about good cosmetic result, and patients have faster recovery by avoid sternotomy
through RT approach.
PMID- 27502135
TI - [Clinical experience of 60 patients underwent three-dimensional video assisted
thoracoscopic mitral valvuloplasty].
AB - OBJECTIVE: To summarize the clinical experience of 60 patients underwent three
dimensional video assisted thoracoscopic mitral valvuloplasty. METHODS: Sixty
patients were enrolled retrospectively from March 2014 to January 2016 in
Department of Cardiacvascular Surgery, Guangdong Cardiovascular Institute. They
underwent three-dimensional video assisted thoracoscopic mitral valvuloplasty.
There were 37 male and 23 female patients. The range of age was 15 to 78 years
(the median age was 47 years). The techniques of mitral valvuloplasty included
chordae tendineae transplantation (53 patients), annuloplasty (58 patients),
posterior leaflet resection (13 patients), anterior leaflet resection (2
patients), commissure resection (1 patient). Their information from charts were
collected. The follow-up time was lasting 3 to 25 months by telephone or
outpatient department interview. The data was analyzed via paired t test or
Wilcoxon signed-rank test. RESULTS: Conversions to mitral valve replacement were
performed for two patients. No patients underwent thoracotomy. The operation time
was (213+/-37) minutes, cardiopulmonary bypass time was (129+/-31) minutes,
aortic cross clamping time was (81+/-21) minutes. Postoperative hospital stay was
(7+/-3) days. During follow-up period, there were no re-operation and no death.
Mitral regurgitation level and New York Heart Association class were both
improved (Z=-6.286, P=0.000, Z=-6.237, P=0.000), respectively. Besides, there was
also no new atrial fibrillation patients. CONCLUSIONS: Not only does three
dimensional video assisted thoracoscopic mitral valvuloplasty maintain the
advantages of 2-Dimensional thoracoscopy, but also have the similar view of
median thoracotomy. This technique showed promising clinical value in the future.
PMID- 27502136
TI - [Clinical outcome of totally thoracoscopic cardiac surgery for mitral valve
replacement: a series of 634 cases].
AB - OBJECTIVE: To summarize the clinical outcome of totally thoracoscopic cardiac
surgery for mitral valve replacement. METHODS: Clinical data of 634 cases
undergoing totally thoracoscopic cardiac surgery for mitral valve replacement
from May 2004 to February 2016 in Department of Thoracoscopic Cardiacsurgery,
Shanghai Yodak Cardiothoracic Hospital was analyzed retrospectively. There were
292 male and 342 female patients, aged from 17 to 68 years with a mean of (45+/
13) years. All the 634 patients had moderate-severe mitral valve stenosis and
(or) incompetence, 263 patients had moderate-severe tricuspid valve incompetence,
356 patients had atrial fibrillation, 46 patients had left atrium thrombosis.
Cardiopulmonary bypass was established with right femoral artery and a single 2
stage venus cannula in the right atrium. The ascending aorta was cross-clamped
and the myocardium was protected by coronary perfusion with cold crystalloid
cardioplegia. Totally thoracoscopic mitral valve replacement were performed.
RESULTS: Thirteen cases had incision expanded and 8 cases had conversions to
sternotomy. Cardiopulmonary bypass and aortic cross-clamp time were (89+/-18)
minutes and (51+/-12) minutes, respectively. Operation time was (3.1+/-1.2)
hours. Mechanical ventilation time and intensive care unit stay were (17+/-6)
hours and (27+/-8) hours, respectively. Postoperation drainage quantity was
(390+/-70) ml. The hospital days was (9.2+/-2.1) days. There were 5 cases in
hospital deaths. Postoperative complications occurred in 42 cases (6.6%),
including 18 cases of right hemoneumothorax, 12 cases of reoperation for
bleeding, 3 cases of perivalvular leakage (reoperation was done in 1 patient), 3
cases of low cardiac output syndrome, 2 cases of acute renal failure, 2 cases of
inferior vena cava injury, 1 case of right femoral artery thrombosis and liver
injury, respectively. The mean duration of follow-up was (58+/-9) months in 608
cases, with a follow-up rate of 96.7% (608/629). Three patients had died during
the period of follow-up caused by congestive heart failure (2 patients) and
stroke (1 patient). Late complication among 605 survivors were 37 cases,
including 32 cases of moderate tricuspid valve insufficiency, 3 cases of stroke,
1 case of perivalvular leakage and infective endocarditis, respectively.There was
no reoperation during the period of follow-up. CONCLUSION: Totally thoracoscopic
cardiac surgery for mitral valve replacement is safe and effective, with unique
superiority and clinical feasible.
PMID- 27502137
TI - [Clinical application of modified minimally cardiopulmonary bypass: compared with
conventional cardiopulmonary bypass].
AB - OBJECTIVE: To evaluate the safety and effects on blood transfusion of modified
minimally cardiopulmonary bypass (CPB). METHODS: From April 2013 to February
2016, 1 103 elective cardiac surgery cases in National Center for Cardiovascular
Diseases China, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking
Union Medical College were prospectively enrolled in the study. Patients
undergoing modified minimally CPB were assigned to mini-CPB group (n=553), the
others undergoing conventional CPB were assigned to conventional group (n=550).
In mini-CPB group, oxygenator with integrated arterial filter, modified minimized
circuit, mini-cardioplegia and vacuum assisted venous drainage(VAVD) were used.
In conventional group, conventional CPB was composed with conventional oxygenator
from the same manufactory, conventional circuit and 1?4 blood cardioplegia.
Analysis was performed with t test, t' test, Wilcoxon rank-sum test, chi(2) test,
and Fisher exact test. RESULTS: No CPB accidents and peri-operative stroke were
observed. There was no statistical difference in postoperative mechanical
ventilation time, length of ICU stay, postoperative complications and mortality
between the two groups. The incidence of erythrocyte transfusion (13.7% vs.
27.6%, chi(2)=32.458, P=0.000) and the incidence of ultrafilter (11.0% vs. 33.7%,
chi(2)=76.019, P=0.000) were lower in the mini-CPB group. Postoperative
hematocrit (M(QR): 32.9 (5.7) vs. 32.2 (5.7), Z=3.403, P=0.001) and 12-hour chest
drainage ((228+/-154) ml vs.(260+/-197) ml, t'=3.004, P=0.003) of mini-CPB were
imporved compared with conventional group. CONCLUSIONS: Modified minimally CPB is
safe. It might reduce erythrocyte transfusion for adult cardiac surgery,
warranting widely adoption.
PMID- 27502139
TI - [The value of postoperative C-reactive protein in predictive diagnosis of
postoperative intra-abdominal septic complications for patients with Crohn
disease].
AB - OBJECTIVE: To analyze the value of postoperative C-reactive protein (CRP) in
predictive diagnosis of postoperative intra-abdominal septic complications (IASC)
for patients with Crohn disease (CD). METHODS: Clinical data of patients with CD
received intestinal resection and anastomosis surgery at Research Institute of
General Surgery, Jinling Hospital from January 2011 to January 2015 were
analyzed. Patients were divided into two groups by whether suffer from IASC 1
month after surgery, including IASC group and no-IASC group. Propensity score
matching method was used to match the general clinical data. A total of 54
patients were analyzed, including IASC 17 cases, no-IASC 37 cases. Postoperative
CRP at 1-day and 3-day were compared between the two groups using t test.
Receiver operator characteristic (ROC) cure was used to analyze the value of
postoperative CRP in predictive diagnosis of IASC. RESULTS: IASC group had higher
levels of CRP at 1-day ((78+/-13) mg/L vs. (54+/-19) mg/L, t=4.633, P=0.000) and
3-day ((103+/-19) mg/L vs. (69+/-21) mg/L, t=5.859, P=0.000) after surgery than
no-IASC group. ROC analysis showed that the CRP 3-day after surgery cut-off point
value of 81.45 mg/L, as used for the predictive diagnosis of IASC, provided a
sensitivity of 94.1%, a specificity of 82.9%, an area under the curve of 0.90,
better than CRP 1-day after surgery. CONCLUSION: Postoperative CRP can be used as
a predictive diagnosis of IASC for CD patients received intestinal resection and
anastomosis surgery.
PMID- 27502138
TI - [Drug coated balloon with paclitaxel for the treatment of symptomatic peripheral
artery disease: early and midterm results].
AB - OBJECTIVE: To evaluate the safety and efficacy of the drug coated balloon (DCB)
with paclitaxel in patients with symptomatic peripheral artery disease (PAD).
METHODS: The clinical data of 18 patients, who were diagnosed as PAD and treated
with DCB from October 2013 to June 2014 in Department of Vascular Surgery,
People's Liberation Army General Hospital, were retrospectively analyzed.Thirteen
male and 5 female patients were in the series, the mean age of the patients was
(65+/-7) years, and the Rutherford's categories were level 3 to 5. Patients were
followed up at 3- and 6-month postoperative. The main efficacy end point were
late lumen loss(LLL), rate of restenosis and clinically driven target lesion
revascularization (TLR). Meanwhile, the clinical events were recorded. RESULTS:
Mean lesion length, the percentage of total occlusions and the percentage of in
stent restenosis were (138+/-91) mm, 9/18 and 2/18, respectively. Rate of
technical success was 18/18. At 6-month postoperative, LLL, rate of restenosis
and TLR were (0.1+/-0.9) mm, 2/14 and 0, respectively. There was no deaths or no
amputations. CONCLUSION: DCB with paclitaxel is safe in patients with PAD, and
associated with reductions in LLL, restenosis and clinically driven TLR 6-month
postoperative.
PMID- 27502140
TI - [Reconstruct abdominal aortic branch arteries totally by endovascular repair in
complex aortic aneurysms: a single-centre experience].
AB - OBJECTIVE: To report experiences and results of complex aortic aneurysms
involving the visceral arteries treating by total endovascular repair. METHODS:
Seventy cases of thoracoabdominal aortic lesions treating by total endovascular
repair in Department of Vascular Surgery, People's Liberation Army General
Hospital from January 2011 to December 2014 were retrospectively analyzed. There
were 47 cases underwent chimney technique, 6 underwent sandwich technique, 15
underwent fenestration technique and 2 underwent branched stent grafts technique.
RESULTS: The average follow-up time was 21 months, range from 3 to 47 months.
Completion angiography showed that typeI endoleak of chimney, sandwich,
fenestration and branched stent grafts group were 9/47, 5/6, 2/15 and 0,
respectively. While at 30-day typeI endoleak reduced to 7/47, 2/6, 0 and 0.
During follow-up, there were 3 target vessel stents occlusion in chimney group,
the patency rate of target vessel stent was 95.1% (58/61). In sandwich,
fenestration and branched stent grafts group, all the target vessel stents kept
patent. CONCLUSION: In this study, chimney, sandwich, fenestration and branched
stent grafts techniques show good short-term and midterm results, the long-term
effects still need further studies.
PMID- 27502141
TI - [The relationship between preoperative renal failure and severe postoperative
hypoxemia of patients received surgical procedures for Stanford A aortic
dissection].
AB - OBJECTIVE: To study the relationship between renal failure and severe
postoperative hypoxemia of patients received surgical procedure for Stanford A
aortic dissection. METHODS: Clinical data of 411 consecutive patients from
January 2014 to April 2015, who received surgical procedure for Stanford A aortic
dissection in Department of Cardiovascular Surgery of Beijing Anzhen Hospital,
were collected retrospectively. The appearance of severe postoperative hypoxemia
was recorded in all the cases. All the data about potential prognostic factors
was put into the database and analyzed by univariate and multivariate Logistic
regression respectively. RESULTS: Severe postoperative hypoxemia (PO2/FiO2<100
mmHg, 1 mmHg=0.133 kPa) happened on 69 cases within 48 hours after procedures,
with the incidence rate of 17.1%. Both univariate and multivariate Logistic
regression indicated the influence that preoperative creatinine clearance rate
had on severe postoperative hypoxemia showed no statistical significance.
However, the influence of preoperative serum creatinine showed statistical
significance (OR=1.009, 95%CI: 1.000 to 1.018, P=0.048). CONCLUSIONS: The
preoperative creatinine clearance rate of patients has no direct relationship
with severe postoperative hypoxemia. But the preoperative serum creatinine could
be regarded as an independent predictor of severe postoperative hypoxemia.
PMID- 27502142
TI - [Effect of prostate volume on the peripheral nerve block anesthesia in prostate
biopsy].
AB - OBJECTIVE: To evaluate the anesthetic efficacy of periprostatic nerve block in
transrectal ultrasound(TRUS) guided biopsy on different prostate volume. METHODS:
A total of 568 patients received prostate biopsy in Department of Urology, Subei
People's Hospital from May 2013 to September 2015 were retrospectively studied.
All patients were divided into local anesthesia group and nerve block group
according to different way of anesthesia. Then each group was divided into four
subgroups(20-40 ml, >40-60 ml, >60-100 ml and >100 ml subgroups) according to
different prostate volume range. After being anaesthetized successfully, patients
in two groups underwent prostate biopsy, visual analogue scale(VAS) scores,
visual numeric scale(VNS)scores and complications were recorded and analyzed. At
inter-group and intra-group in local anesthesia group and nerve block group, Mann
Whitney U test of non-parametric analysis and single factor variance analysis
were used to compare the VAS scores and the VNS scores respectively, and chi
square test was used to compare the rates of complication. RESULTS: The VAS
scores of four subgroups: local anesthesia group: 1.9+/-0.9, 2.8+/-1.5, 3.8+/-2.3
and 5.3+/-2.5; nerve block group: 1.5+/-0.7, 2.0+/-0.8, 2.9+/-1.7 and 4.2+/-2.0.
The VNS scores: local anesthesia group: 3.4+/-0.6, 2.9+/-0.6, 2.7+/-0.5 and 1.6+/
0.7; nerve block group: 3.7+/-0.5, 3.3+/-0.4, 3.0+/-0.8 and 2.0+/-0.7. The VAS
scores and the VNS scores had significant differences (Z=-3.637-98.253, all
P<0.05) at inter-group or intra-group level. For the complication rates of
operation, hematuria, blood, urinary retention were significant differences
(F=1.347-15.402, all P<0.05) at intra-group level. But there were no significant
differences at inter-group level(P>0.05). CONCLUSION: Compared with local
anesthesia, ultrasound guided prostate peripheral nerve block anesthesia has
great analgesic effect and high safety, but for patients with a large prostate
volumethe analgesic effect is inefficiency.
PMID- 27502143
TI - IgG subclass co-expression brings harmony to the quartet model of murine IgG
function.
AB - A model of murine IgG function is presented in which the co-expression of the IgG
subclasses is a central feature, class switching occurs before the commencement
of somatic hypermutation, and there is little switching between subclasses. It is
named the quartet model to emphasize the harmony that comes from the simultaneous
presence of the four subclasses. In this model, IgG3 and IgG2b antibodies are
particularly important early in the response, when T-cell help may be limiting.
IgG3 initiates inflammation through complement fixation, whereas IgG2b provides
early FcgammaR-mediated effector functions. As T-cell help strengthens, IgG2a
antibodies increase the power of the response, whereas IgG1 production helps
limit the inflammatory drive and limits immunopathology. The model highlights the
fact that murine IgG subclasses function quite differently to human IgG
subclasses. This allows them to serve the special immunological needs of a
species that is vulnerable because of its small size.
PMID- 27502145
TI - Making a mes: A transcription factor-microRNA pair governs the size of the
midbrain and the dopaminergic progenitor pool.
AB - Canonical Wnt signaling is critical for midbrain dopaminergic progenitor
specification, proliferation, and neurogenesis. Yet mechanisms that control Wnt
signaling remain to be fully elucidated. Wnt1 is a key ligand in the embryonic
midbrain, and directs proliferation, survival, specification and neurogenesis. In
a recent study, we reveal that the transcription factor Lmx1b promotes Wnt1/Wnt
signaling, and dopaminergic progenitor expansion, consistent with earlier
studies. Additionally, Lmx1b drives expression of a non-coding RNA called Rmst,
which harbors miR135a2 in its last intron. miR135a2 in turn targets Lmx1b as well
as several Wnt pathway targets. Conditional overexpression of miR135a2 in the
midbrain, particularly during an early time, results in a decreased dopaminergic
progenitor pool, and less dopaminergic neurons, consistent with decreased Wnt
signaling. We propose a model in which Lmx1b and miR135a2 influence levels of
Wnt1 and Wnt signaling, and expansion of the dopaminergic progenitor pool.
Further loss of function experiments and biochemical validation of targets will
be critical to verify this model. Wnt agonists have recently been utilized for
programming stem cells toward a dopaminergic fate in vitro, highlighting the
importance of agents that modulate the Wnt pathway.
PMID- 27502144
TI - Effects of transmission-blocking vaccines simultaneously targeting pre- and post
fertilization antigens in the rodent malaria parasite Plasmodium yoelii.
AB - BACKGROUND: Transmission-blocking vaccine (TBV) is a promising strategy for
interrupting the malaria transmission cycle. Current TBV candidates include both
pre- and post-fertilization antigens expressed during sexual development of the
malaria parasites. METHODS: We tested whether a TBV design combining two sexual
stage antigens has better transmission-blocking activity. Using the rodent
malaria model Plasmodium yoelii, we pursued a DNA vaccination strategy with genes
encoding the gametocyte antigen Pys48/45 and the major ookinete surface protein
Pys25. RESULTS: Immunization of mice with DNA constructs expression either
Pys48/45 or Pys25 elicited strong antibody responses, which specifically
recognized a ~45 and ~25 kDa protein from gametocyte and ookinete lysates,
respectively. Immune sera from mice immunized with DNA constructs expressing
Pys48/45 and Pys25 individually and in combination displayed evident transmission
blocking activity in in vitro ookinete culture and direct mosquito feeding
experiments. With both assays, the Pys25 sera had higher transmission-blocking
activity than the Pys48/45 sera. Intriguingly, compared with the immunization
with the individual DNA vaccines, immunization with both DNA constructs produced
lower antibody responses against individual antigens. The resultant immune sera
from the composite vaccination had significantly lower transmission-blocking
activity than those from Pys25 DNA immunization group, albeit the activity was
substantially higher than that from the Pys48 DNA vaccination group. CONCLUSIONS:
This result suggested that vaccination with the two DNA constructs did not
achieve a synergistic effect, but rather caused interference in inducing antigen
specific antibody responses. This result has important implications for future
design of composite vaccines targeting different sexual antigens.
PMID- 27502146
TI - Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.
AB - Over the last few decades, polymers have been extensively used as pharmaceutical
excipients in drug delivery systems. Pharmaceutical polymers evolved from being
simply used as gelatin shells comprising capsule to offering great formulation
advantages including enabling controlled/slow release and specific targeting of
drugs to the site(s) of action (the "magic bullets" concept), hence hold a
significant clinical promise. Oral administration of solid dosage forms (e.g.,
tablets and capsules) is the most common and convenient route of drug
administration. When formulating challenging molecules into solid oral dosage
forms, polymeric pharmaceutical excipients permit masking undesired
physicochemical properties of drugs and consequently, altering their
pharmacokinetic profiles to improve the therapeutic effect. As a result, the
number of synthetic and natural polymers available commercially as pharmaceutical
excipients has increased dramatically, offering potential solutions to various
difficulties. For instance, the different polymers may allow increased
solubility, swellability, viscosity, biodegradability, advanced coatings, pH
dependency, mucodhesion, and inhibition of crystallization. The aim of this
article is to provide a wide angle prospect of the different uses of
pharmaceutical polymers in solid oral dosage forms. The various types of
polymeric excipients are presented, and their distinctive role in oral drug
delivery is emphasized. The comprehensive know-how provided in this article may
allow scientists to use these polymeric excipients rationally, to fully exploit
their different features and potential influence on drug delivery, with the
overall aim of making better drug products.
PMID- 27502147
TI - 5-(2-Aminopropyl)benzofuran and phenazepam demonstrate the possibility of
dependence by increasing dopamine levels in the brain.
AB - Although 5-(2-aminopropyl)benzofuran (5-APB) and 7-bromo-5-(2-chlorophenyl)-1,3
dihydro-2H-1,4-benzodiazepin-2-one (phenazepam) are being used as recreational
drugs, research on their dependence liability or mechanisms of action is lacking.
The present study aimed to evaluate the behavioral effects and dependence
liability of these drugs using conditioned place preference and self
administration paradigms in rodents. Additionally, biochemical techniques were
used to assess the substance-induced alterations in synaptosome-released
dopamine. While both of the tested substances elicited increases in conditioned
place preference and dopamine, neither of them facilitated self-administration,
suggesting that 5-APB and phenazepam have rewarding effects, rather than
reinforcing effects.
PMID- 27502148
TI - Cutting edge issues in autoimmune hepatitis.
AB - Autoimmune hepatitis (AIH) is a severe liver disease affecting all age groups
worldwide. Novel basic and clinical aspects of AIH, addressed at a Monothematic
Conference in London in September 2015, are highlighted in this review. The
diagnosis of AIH relies upon detection of characteristic autoantibodies,
hypergammaglobulinemia, and interface hepatitis on liver histology. The
International Autoimmune Hepatitis Group (IAIHG) has devised diagnostic scoring
systems to help in comparative studies and clinical practice. AIH arises in a
genetically predisposed host, when yet unknown triggers - such an encounter with
a pathogen - lead to a T cell-mediated immune response targeting liver
autoantigens. This immune response is inadequately controlled because regulatory
mechanisms are impaired. The mainstay of treatment for AIH is immunosuppression,
which should be instituted as soon as the diagnosis is made. Standard treatment
regimens include relatively high doses of predniso(lo)ne, which are tapered
gradually as azathioprine is introduced. Recent guidelines have described newer
treatment regimens and have tightened the goal of therapy to complete
normalization of biochemical, serological and histological parameters.
Mycophenolate mofetil, calcineurin inhibitors, mTOR inhibitors and biological
agents are potential salvage therapies, but should be reserved for selected non
responsive patients and administered only in experienced centers. Liver
transplantation is a life-saving option for those patients who progress to end
stage liver disease. Further dissection of cellular and molecular pathways
involved in AIH pathogenesis is likely to lead to the discovery of novel,
tailored and better tolerated therapies.
PMID- 27502149
TI - Retrospective evaluation of 211 patients with maxillofacial reconstruction using
parietal bone graft for implants insertion.
AB - PURPOSE: For a century, autologous bone grafts have been used in maxillofacial
reconstruction. The ideal bone harvest site and grafting procedure remains a
point of contention in regards to obtaining optimal long-term results with
sufficient bone quantity and density without serious complications. More
recently, confronted with growing patient requests and biomaterials development,
maxillofacial surgeons and dentists have been considering these issues as they
relate to pre-implant surgery. This study sought to evaluate implant success rate
and complications following pre-implant surgery with parietal bone grafting.
MATERIALS AND METHODS: A retrospective study was carried out on patients who
underwent maxillofacial reconstruction of different sites (symphysis, mandibular
corpus, maxillary sinus and premaxilla) for the purpose of implant insertion.
RESULTS: 311 procedures in 211 patients were included. The implant
osseointegration rate was around 95%. Clinical follow-up ranged from 10 months to
11 years. A secondary procedure was performed in 6.1% of cases and we noted no
serious complications at the harvest site. DISCUSSION: With good
revascularization and osseointegration of the graft, the use of parietal bone
leads to an implant success rate similar to that seen in the literature.
Moreover, the use of this material results in few infections and low bone
resorption provided there is strict immobilization of the graft and no tension on
the soft tissue sutures. CONCLUSION: Parietal bone grafts technique possess the
required qualities for the success of implant surgery, offering results at least
as interesting as others using autogenous bone and with no serious complications
on donor site.
PMID- 27502151
TI - Comparative cytotoxic and genotoxic effects of permethrin and its nanometric form
on human erythrocytes and lymphocytes in vitro.
AB - The research on the novel pesticides such as nanopesticides has become inevitable
to control the mosquito population. Nanopermethrin (NP), one of such kind was
formulated in pesticide loaded oil-in-water (o/w) microemulsion by rapid
evaporation. Even though NP possess improved efficacy against the target pests,
the toxicological investigation on the human or mammalian system remains
unexplored. So, the present study focused on a comparative investigation of the
cytotoxic and genotoxic effects of NP in vitro and its commercial parental bulk
form of permethrin (BP) on human peripheral erythrocyte/lymphocyte by erythrocyte
morphology analysis, cell viability assay, and cytokinesis-block micronucleus
(CBMN) assay. The NP and BP concentrations (10, 25, 50 and 100 MUg/ml) interacted
with human blood cells, and the morphological changes were observed using a phase
contrast microscope. The drastic increase of echinocyte was observed at 24, 48
and 72 h treatment as compared with the control. The cell viability studies have
shown the significant decrease with increase in NP and BP concentration. CBMN
study showed a series correlation in the number of micronuclei, bridge, bud,
trinucleated and tetranucleated when interacted with different levels of NP and
BP, as comparative to control *p < 0.05, **p < 0.001, ***p < 0.0001.
PMID- 27502150
TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppress AChE activity in NGF treated PC12
cells.
AB - PC12 is a well studied cell model for neuronal differentiation. AChE is also
considered as a marker for neuronal differentiation. In this study, we detected
the change of AChE activity during the NGF induced differentiation of PC 12
cells, and targeted on the ratio of the activity of AChE on the cell surface, and
found that NGF mainly increased the intracellular AChE activity. Dioxin is a kind
of persistent organic pollutants which have extreme impact on human health and
widely distributed all over the world. Recently, AChE was reported as a target of
the toxicity of dioxin. Here we investigated the effect of 2,3,7,8
tetrachlorodibenzo-p-dioxin (TCDD) on AChE activity in the PC12 cells, and found
that at the later stage of differentiation, TCDD could decrease the AChE
activity. This down regulation might not related to transcriptional regulation.
PMID- 27502152
TI - 25-hydroxyvitamin D in malignant pleural disease: a prospective cohort study.
AB - INTRODUCTION: Growing evidence suggests a role of vitamin D in various cancers
but the significance of vitamin D in malignant pleural disease remains
unexplored. We sought to investigate the concentration and diagnostic role of 25
hydroxyvitamin D (25(OH)D) in malignant pleural effusions. MATERIALS AND METHODS:
Prospective study of consecutive treatment-naive patients with a new diagnosis of
pleural effusion. RESULTS: Seventy-eight patients were studied, 45 of whom had
malignant pleural effusions. Concentration of 25(OH)D in pleural fluid was
significantly higher than serum in both malignant (15.2 ng/mL (9.7, 25.6) versus
10.2 ng/mL (6.4, 17.7), P < .001) and benign (11.4 ng/mL (8.4, 23.6) versus 7.9
(5.9, 16.1), P < .001) pleural disease. Pleural fluid 25(OH)D was almost
significantly higher in exudates compared to transudates (P = .050) but it did
not differ significantly between malignant and benign effusions (P = .217) and it
was not diagnostic for malignant pleural disease (area under the ROC curve .58,
95% CI .45-.71). CONCLUSIONS: In subjects with unselected pleural effusions,
25(OH)D in pleural fluid was not diagnostic for malignant pleural disease. The
novel finding of convincingly and consistently higher 25(OH)D in pleural fluid
than serum suggests a role for vitamin D in pleural disease and merits further
research.
PMID- 27502154
TI - Role of block copolymer adsorption versus bimodal grafting on nanoparticle self
assembly in polymer nanocomposites.
AB - We compare the self-assembly of silica nanoparticles (NPs) with physically
adsorbed polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) copolymers (BCP)
against NPs with grafted bimodal (BM) brushes comprised of long, sparsely grafted
PS chains and a short dense carpet of P2VP chains. As with grafted NPs, the
dispersion state of the BCP NPs can be facilely tuned in PS matrices by varying
the PS coverage on the NP surface or by changes in the ratio of the PS graft to
matrix chain lengths. Surprisingly, the BCP NPs are remarkably better dispersed
than the NPs tethered with bimodal brushes at comparable PS grafting densities.
We postulate that this difference arises because of two factors inherent in the
synthesis of the NPs: In the case of the BCP NPs the adsorption process is
analogous to the chains being "grafted to" the NP surface, while the BM case
corresponds to "grafting from" the surface. We have shown that the "grafted from"
protocol yields patchy NPs even if the graft points are uniformly placed on each
particle. This phenomenon, which is caused by chain conformation fluctuations, is
exacerbated by the distribution function associated with the (small) number of
grafts per particle. In contrast, in the case of BCP adsorption, each NP is more
uniformly coated by a P2VP monolayer driven by the strongly favorable P2VP-silica
interactions. Since each P2VP block is connected to a PS chain we conjecture that
these adsorbed systems are closer to the limit of spatially uniform sparse brush
coverage than the chemically grafted case. We finally show that the better NP
dispersion resulting from BCP adsorption leads to larger mechanical reinforcement
than those achieved with BM particles. These results emphasize that physical
adsorption of BCPs is a simple, effective and practically promising strategy to
direct NP dispersion in a chemically unfavorable polymer matrix.
PMID- 27502153
TI - Motivating factors and barriers towards exercise in severe mental illness: a
systematic review and meta-analysis.
AB - Exercise can improve clinical outcomes in people with severe mental illness
(SMI). However, this population typically engages in low levels of physical
activity with poor adherence to exercise interventions. Understanding the
motivating factors and barriers towards exercise for people with SMI would help
to maximize exercise participation. A search of major electronic databases was
conducted from inception until May 2016. Quantitative studies providing
proportional data on the motivating factors and/or barriers towards exercise
among patients with SMI were eligible. Random-effects meta-analyses were
undertaken to calculate proportional data and 95% confidence intervals (CI) for
motivating factors and barriers toward exercise. From 1468 studies, 12
independent studies of 6431 psychiatric patients were eligible for inclusion.
Meta-analyses showed that 91% of people with SMI endorsed 'improving health' as a
reason for exercise (N = 6, n = 790, 95% CI 80-94). Among specific aspects of
health and well-being, the most common motivations were 'losing weight' (83% of
patients), 'improving mood' (81%) and 'reducing stress' (78%). However, low mood
and stress were also identified as the most prevalent barriers towards exercise
(61% of patients), followed by 'lack of support' (50%). Many of the desirable
outcomes of exercise for people with SMI, such as mood improvement, stress
reduction and increased energy, are inversely related to the barriers of
depression, stress and fatigue which frequently restrict their participation in
exercise. Providing patients with professional support to identify and achieve
their exercise goals may enable them to overcome psychological barriers, and
maintain motivation towards regular physical activity.
PMID- 27502155
TI - Natural and synthetic peptides with antifungal activity.
AB - In recent years, the increase of invasive fungal infections and the emergence of
antifungal resistance stressed the need for new antifungal drugs. Peptides have
shown to be good candidates for the development of alternative antimicrobial
agents through high-throughput screening, and subsequent optimization according
to a rational approach. This review presents a brief overview on antifungal
natural peptides of different sources (animals, plants, micro-organisms), peptide
fragments derived by proteolytic cleavage of precursor physiological proteins
(cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal
peptides are schematically reported based on their structure, antifungal spectrum
and reported effects. Natural or synthetic peptides and their modified
derivatives may represent the basis for new compounds active against fungal
infections.
PMID- 27502156
TI - Forizymes - functionalised artificial forisomes as a platform for the production
and immobilisation of single enzymes and multi-enzyme complexes.
AB - The immobilisation of enzymes plays an important role in many applications,
including biosensors that require enzyme activity, stability and recyclability in
order to function efficiently. Here we show that forisomes (plant-derived
mechanoproteins) can be functionalised with enzymes by translational fusion,
leading to the assembly of structures designated as forizymes. When forizymes are
expressed in the yeast Saccharomyces cerevisiae, the enzymes are immobilised by
the self-assembly of forisome subunits to form well-structured protein bodies. We
used glucose-6-phosphate dehydrogenase (G6PDH) and hexokinase 2 (HXK2) as model
enzymes for the one-step production and purification of catalytically active
forizymes. These structures retain the typical stimulus-response reaction of the
forisome and the enzyme remains active even after multiple assay cycles, which we
demonstrated using G6PDH forizymes as an example. We also achieved the co
incorporation of both HXK2 and G6PDH in a single forizyme, facilitating a two
step reaction cascade that was 30% faster than the coupled reaction using the
corresponding enzymes on different forizymes or in solution. Our novel forizyme
immobilisation technique therefore not only combines the sensory properties of
forisome proteins with the catalytic properties of enzymes but also allows the
development of multi-enzyme complexes for incorporation into technical devices.
PMID- 27502157
TI - Evolution of a Protein Interaction Domain Family by Tuning Conformational
Flexibility.
AB - Conformational flexibility allows proteins to adopt multiple functionally
important conformations but can also lead to nonfunctional structures. We
analyzed the dynamic behavior of the enzyme guanylate kinase as it evolved into
the GK protein interaction domain (GKPID) to investigate the role of flexibility
in the evolution of new protein functions. We found that the ancestral enzyme is
very flexible, allowing it to adopt open conformations that can bind nucleotide
and closed ones that enable catalysis of phosphotransfer from ATP to GMP.
Historical mutations that converted the GK from an enzyme to a protein
interaction domain dramatically reduce flexibility, predominantly by inhibiting
rotations of the protein backbone that are coupled to the global closing motion.
Removing flexibility prevents adoption of conformations that cannot fit the
protein partner in the binding site. Our results highlight the importance of
mutations that optimize protein conformational flexibility with function during
evolution.
PMID- 27502158
TI - Cardiorespiratory fitness as a predictor of intestinal microbial diversity and
distinct metagenomic functions.
AB - BACKGROUND: Reduced microbial diversity in human intestines has been implicated
in various conditions such as diabetes, colorectal cancer, and inflammatory bowel
disease. The role of physical fitness in the context of human intestinal
microbiota is currently not known. We used high-throughput sequencing to analyze
fecal microbiota of 39 healthy participants with similar age, BMI, and diets but
with varying cardiorespiratory fitness levels. Fecal short-chain fatty acids were
analyzed using gas chromatography. RESULTS: We showed that peak oxygen uptake
(VO2peak), the gold standard measure of cardiorespiratory fitness, can account
for more than 20 % of the variation in taxonomic richness, after accounting for
all other factors, including diet. While VO2peak did not explain variation in
beta diversity, it did play a significant role in explaining variation in the
microbiomes' predicted metagenomic functions, aligning positively with genes
related to bacterial chemotaxis, motility, and fatty acid biosynthesis. These
predicted functions were supported by measured increases in production of fecal
butyrate, a short-chain fatty acid associated with improved gut health, amongst
physically fit participants. We also identified increased abundances of key
butyrate-producing taxa (Clostridiales, Roseburia, Lachnospiraceae, and
Erysipelotrichaceae) amongst these individuals, which likely contributed to the
observed increases in butyrate levels. CONCLUSIONS: Results from this study show
that cardiorespiratory fitness is correlated with increased microbial diversity
in healthy humans and that the associated changes are anchored around a set of
functional cores rather than specific taxa. The microbial profiles of fit
individuals favor the production of butyrate. As increased microbiota diversity
and butyrate production is associated with overall host health, our findings
warrant the use of exercise prescription as an adjuvant therapy in combating
dysbiosis-associated diseases.
PMID- 27502159
TI - Acetate ions enhance load and stability of doxorubicin onto PEGylated nanodiamond
for selective tumor intracellular controlled release and therapy.
AB - A successful drug delivery device for cancer chemotherapy should ideally be able
to load drugs highly, bring the drug preferentially into tumor cells and reduce
its distribution in normal tissue to enhance therapeutic efficacy. To this
purpose, a novel protocol for DOX-loaded PEGylated nanodiamond (ND-PEG-DOX/NaAc,
NPDA) was fabricated using sodium acetate medium. The NPDA nanoparticles
exhibited a maximum loading efficiency (99 wt%) with ultra-low drug leakage (7
wt%). Examination by confocal microscope and flow cytometer showed that the NPDA
uptake by cells was time-dependent, with a slow and sustained drug release from
the lysosomes at a low pH. Also, when CHO (a normal cell) and MCF-7 (a cancer
cell) were treated with NPDA, the results demonstrated that NPDA preferentially
accumulated much more in tumor cells than in normal cells, which implied that
NPDA has the ability to selectively kill tumor cells. In addition, NPDA can
inhibit the migration and proliferation of tumor cells and change the cell cycle
compared to the free drug. Outcomes from this work suggest that NPDA would be a
promising drug delivery platform and the preparation of such a drug delivery
system will also have implications in improving the biomedical applications of
smart nanodiamond carriers.
PMID- 27502160
TI - Nanostructured Tendon-Derived Scaffolds for Enhanced Bone Regeneration by Human
Adipose-Derived Stem Cells.
AB - Decellularized matrix-based scaffolds can induce enhanced tissue regeneration due
to their biochemical, biophysical, and mechanical similarity to native tissues.
In this study, we report a nanostructured decellularized tendon scaffold with
aligned, nanofibrous structures to enhance osteogenic differentiation and in vivo
bone formation of human adipose-derived stem cells (hADSCs). Using a bioskiving
method, we prepared decellularized tendon scaffolds from tissue slices of bovine
Achilles and neck tendons with or without fixation, and investigated the effects
on physical and mechanical properties of decellularized tendon scaffolds, based
on the types and concentrations of cross-linking agents. In general, we found
that decellularized tendon scaffolds without fixative treatments were more
effective in inducing osteogenic differentiation and mineralization of hADSCs in
vitro. When non-cross-linked decellularized tendon scaffolds were applied
together with hydroxyapatite for hADSC transplantation in critical-sized bone
defects, they promoted bone-specific collagen deposition and mineralized bone
formation 4 and 8 weeks after hADSC transplantation, compared to conventional
collagen type I scaffolds. Interestingly, stacking of decellularized tendon
scaffolds cultured with osteogenically committed hADSCs and those containing
human cord blood-derived endothelial progenitor cells (hEPCs) induced
vascularized bone regeneration in the defects 8 weeks after transplantation. Our
study suggests that biomimetic nanostructured scaffolds made of decellularized
tissue matrices can serve as functional tissue-engineering scaffolds for enhanced
osteogenesis of stem cells.
PMID- 27502161
TI - School performance for children with cleft lip and palate: a population-based
study.
AB - BACKGROUND: Educational attainment is important in shaping young people's life
prospects. To investigate whether being born with orofacial cleft (OFC) affects
school performance, we compared school test results between children born with
and without OFC. METHODS: Using record-linked datasets, we conducted a population
based cohort study of children liveborn in Western Australia 1980-2010 with a
diagnosis of OFC on the Register of Developmental Anomalies, and a random sample
of 6603 children born without OFC. We compared odds ratios for meeting national
minimum standards in five domains (reading, numeracy, writing, spelling, grammar
and punctuation), and adjusted OR (aOR) for children with cleft lip only (CLO),
cleft lip and palate (CL + P) and cleft palate only (CPO) for each domain.
RESULTS: Results from two testing programs (WALNA and NAPLAN) were available for
3238 (89%) children expected to participate. Most met the national minimum
standards. Compared with children without OFC, children with CPO were less likely
to meet minimum standards for NAPLAN reading (aOR 0.57 [95%CI 0.34, 0.96])
grammar and punctuation (aOR 0.49 [95%CI 0.32, 0.76]), WALNA writing (aOR 0.66
[95%CI 0.47, 0.92]), and WALNA and NAPLAN numeracy (aOR 0.64 [95%CI 0.43, 0.95]
and aOR 0.47 [95%CI 0.28, 0.82]), respectively. Children with CL + P had
significantly lower odds for reaching the spelling standard in NAPLAN tests (aOR
0.52 [95%CI 0.29, 0.94]). Children with CLO had similar odds for reaching all
minimum standards. CONCLUSION: Children born with OFC, particularly children with
CPO, should be monitored to identify learning difficulties early, to enable
intervention to maximize school attainment.
PMID- 27502162
TI - Identifying the Leading Edge of Exceptionally Long Contaminant Plumes.
PMID- 27502163
TI - Ribosomal protein L18aB is required for both male gametophyte function and embryo
development in Arabidopsis.
AB - Ribosomal proteins are involved in numerous essential cell activities in plants.
However, the regulatory role in specific plant developmental processes has not
yet been fully elucidated. Here we identified the new ribosomal protein L18aB,
which is specifically involved in sexual reproduction and plays a critical role
in male gametophyte development and embryo pattern formation. In rpl18aB mutant
plants, the mature pollen grains can germinate normally, but their
competitiveness for growing in the style is significantly reduced. More
interestingly, RPL18aB is required in early embryogenesis. rpl18aB embryos
displayed irregular cell division orientations in the early pro-embryo and
arrested at the globular stage with possible, secondary pattern formation
defects. Further investigations revealed that the polar transportation of auxin
is disturbed in the rpl18aB mutant embryos, which may explain the observed
failure in embryo pattern formation. The cell type-specific complementation of
RPL18aB in rpl18aB was not able to recover the phenotype, indicating that RPL18aB
may play an essential role in early cell fate determination. This work unravels a
novel role in embryo development for a ribosomal protein, and provides insight
into regulatory mechanism of early embryogenesis.
PMID- 27502164
TI - Downregulation of miR-3940-5p promotes T-cell activity by targeting the cytokine
receptor IL-2R gamma on human cutaneous T-cell lines.
AB - Vitiligo is a common established depigmentation skin disease characterized by the
presence of activated T lymphocytes anti melanocytes within the skin. T-cell
immunity mainly mediates the destruction of melanocytes and is one of the main
mechanisms involved in the pathogenesis of non-segmental vitiligo. Our previous
study had identified several differentially expressed miRNAs and found that the
expression of miR-3940-5p was downregulated in vitiligo patients. According to
the research findings, we hypothesized that the novel miRNA plays a potential
role on human cutaneous T lymphocytes in the action mechanism of immune imbalance
in vitiligo.
PMID- 27502165
TI - Dock10 regulates CD23 expression and sustains B-cell lymphopoiesis in secondary
lymphoid tissue.
AB - Dock10, a guanine nucleotide exchange factor for the Rho GTPases Rac1 and Cdc42,
affects cell morphology, membrane protrusive activity, and cell movement. Dock10
is prominently expressed in lymphoid tissue and upregulated by IL-4 in B cells.
To investigate the physiological role of Dock10, WT mice and Dock10 KO mice were
used. KO mice showed decreased numbers of B cells in spleen, both follicular B
cells and marginal zone B cells, and in peripheral blood, but not in bone marrow.
The antiapoptotic effect of IL-4 in vitro, the migratory response to CXCL13 or
CCL21 in vitro, and the whole genome expression profile were intact in spleen B
cells from KO mice. CD23, the low-affinity receptor for immunoglobulin E, was
overexpressed on follicular B cells from KO mice, suggesting that Dock10
negatively regulates membrane CD23 expression. Negative regulation of CD23
expression by Dock10 could play a role in B cell maturation and function.
PMID- 27502166
TI - Impact of cartilage graft size on success of tympanoplasty.
AB - INTRODUCTION: In the last decade, there has been an increasing use of cartilage
grafts in the primary repair of tympanic membrane perforations. The major
advantages of cartilage are its stiffness and its very low metabolic
requirements, which make it particularly suitable for difficult conditions, such
as subtotal perforations, adhesive otitis and reoperation. OBJECTIVE: To analyze
the impact of different perforation sizes requiring different sizes of cartilage
on the anatomical and functional outcome after tympanoplasty. METHODS: Through
this prospective non-controlled, non-randomized study, 50 patients underwent
cartilage type 1 tympanoplasty (20 females and 30 males), with a mean age of
19.3+/-9.8 years. According to size of perforation, patients were subdivided into
three groups, Group I had perforation >50% of tympanic membrane area, in Group II
patients the perforations were 25-50% of tympanic membrane area, and in Group III
the perforations were <=25% of tympanic membrane. All patients had pre and
postoperative Pure Tone Average and Air Bone Gap frequencies (0.5, 1, 2, 4kHz).
All patients were followed up at least 12 months after operation. RESULTS: The
anatomical success rate among all patients was 92%, all groups showed statistical
significant improvement between pre and postoperative air bone gap, no
significant correlation between size of cartilage graft and degree of air bone
gap improvement was noticed among the three groups. CONCLUSION: Size of a
cartilage graft has no impact on degree of hearing improvement or anatomical
success rate after tympanoplasty.
PMID- 27502167
TI - Desulfation of cell surface HSPG is an effective strategy for the treatment of
gallbladder carcinoma.
AB - Cell surface heparan sulfate proteoglycan (HSPG) is a group of critical
glycoproteins that mediates signal transduction. Sulfated HSPG can mediate the
activation of a variety of cell growth factor signal pathway to promote the
progression of gallbladder carcinoma (GBC). This study analyzed 527 clinical GBC
specimens and confirmed that the HSPG sulfation level was significantly higher in
GBC tissues than in gallbladder mucosa (GBM) tissues. The high HSPG sulfation
level was closely associated with poor differentiation, local metastasis, and
advanced clinical stage of GBC; it was also associated with the shortening of
disease-free survival (DFS) and overall survival (OS) and influenced the outcome
of chemotherapy or radio-chemotherapy in patients with GBC recurrence. Inhibition
of HSPG sulfation on the GBC cell surface using human sulfatase 1 (hSulf-1)
significantly reduced the phosphorylation levels of growth factor receptors and
signaling protein kinases in GBC cells, decreased cell responses to growth
factors, and inhibited cell proliferation and migration abilities. In a nude
mouse model with GBC xenografts, we observed that the xenograft tumor growth was
suppressed and the phosphorylation levels of signaling proteins were
downregulated, together with decreased expression of Ki67 and reduced sensitivity
to bFGF (basic fibroblast growth factor) induction after inhibition of HSPG
sulfation. Our study demonstrated that a high HSPG sulfation endows GBC with high
malignant biological behaviors and a poor prognosis. Desulfation of cell surface
HSPG can inhibit the kinase activities of a variety of signaling proteins, hinder
the cell response to growth factors, and effectively inhibit the malignant
biological behaviors of GBC cells.
PMID- 27502169
TI - The modular approach enables a fully ab initio simulation of the contacts between
3D and 2D materials.
AB - Up to now, the electrical properties of the contacts between 3D metals and 2D
materials have never been computed at a fully ab initio level due to the huge
number of atomic orbitals involved in a current path from an electrode to a
pristine 2D material. As a result, there are still numerous open questions and
controversial theories on the electrical properties of systems with 3D/2D
interfaces-for example, the current path and the contact length scalability. Our
work provides a first-principles solution to this long-standing problem with the
use of the modular approach, a method which rigorously combines a Green function
formalism with the density functional theory (DFT) for this particular contact
type. The modular approach is a general approach valid for any 3D/2D contact. As
an example, we apply it to the most investigated among 3D/2D contacts
metal/graphene contacts-and show its abilities and consistency by comparison with
existing experimental data. As it is applicable to any 3D/2D interface, the
modular approach allows the engineering of 3D/2D contacts with the pre-defined
electrical properties.
PMID- 27502168
TI - The efficient elimination of solid tumor cells by EGFR-specific and HER2-specific
scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F.
AB - Antibody-drug conjugates (ADCs) combine the potency of cytotoxic drugs with the
specificity of monoclonal antibodies (mAbs). Most ADCs are currently generated by
the nonspecific conjugation of drug-linker reagents to certain amino acid
residues in mAbs, resulting in a heterogeneous product. To overcome this
limitation and prepare ADCs with a defined stoichiometry, we use SNAP-tag
technology as an alternative conjugation strategy. This allows the site-specific
conjugation of O(6)-benzylguanine (BG)-modified small molecules to SNAP-tag
fusion proteins. To demonstrate the suitability of this system for the
preparation of novel recombinant ADCs, here we conjugated SNAP-tagged single
chain antibody fragments (scFvs) to a BG-modified version of auristatin F
(AURIF). We used two scFv-SNAP fusion proteins targeting members of the epidermal
growth factor receptor (EGFR) family that are frequently overexpressed in breast
cancer. The conjugation of BG-AURIF to EGFR-specific 425(scFv)-SNAP and HER2
specific alphaHER2(scFv)-SNAP resulted in two potent recombinant ADCs that
specifically killed breast cancer cell lines by inducing apoptosis when applied
at nanomolar concentrations. These data confirm that SNAP-tag technology is a
promising tool for the generation of novel recombinant ADCs.
PMID- 27502170
TI - Normal saline versus lower-chloride solutions for kidney transplantation.
AB - BACKGROUND: The ideal intravenous fluid for kidney transplantation has not been
defined, despite the common use of normal saline during the peri-operative
period. The high chloride content of normal saline is associated with an
increased risk of hyperchloraemic metabolic acidosis, which may in turn increase
the risk of hyperkalaemia and delayed graft function. Balanced electrolyte
solutions have a lower chloride content which may decrease this risk and avoid
the need for dialysis due to hyperkalaemia in the immediate post-transplant
period. Randomised controlled trials (RCTs) addressing this issue have used
biochemical outcomes to compare fluids and have been underpowered to address
patient-centred outcomes such as delayed graft function. OBJECTIVES: To examine
the effect of lower-chloride solutions versus normal saline on delayed graft
function, hyperkalaemia and acid-base status in kidney transplant recipients.
SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised
Register to 26 November 2015 through contact with the Information Specialist
using search terms relevant to this review. SELECTION CRITERIA: RCTs of kidney
transplant recipients that compared peri-operative intravenous lower-chloride
solutions to normal saline were included. DATA COLLECTION AND ANALYSIS: Two
independent investigators assessed studies for eligibility and risk of bias. Data
from individual studies were extracted using standardised forms and pooled
according to a published protocol. Summary estimates of effect were obtained
using a random-effects model, and results were expressed as risk ratios (RR) and
their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference
(MD) and 95% CI for continuous outcomes. MAIN RESULTS: Six studies (477
participants) were included in the review. All participants were adult kidney
transplant recipients and 70% of participants underwent live-donor kidney
transplantation. The overall risk of bias was low for selection bias and unclear
for remaining domains. There was no difference in the risk of delayed graft
function (3 studies, 298 participants: RR 1.03, 95% CI 0.62 to 1.70) or
hyperkalaemia (2 studies, 199 participants: RR 0.48, 95% CI 0.04 to 6.10) for
participants who received balanced electrolyte solutions compared to normal
saline. Intraoperative balanced electrolyte solutions compared to normal saline
were associated with higher blood pH (3 studies, 193 participants: MD 0.07, 95%
CI 0.05 to 0.09), higher serum bicarbonate (3 studies, 215 participants: MD 3.02
mEq/L, 95% CI 2.00 to 4.05) and lower serum chloride (3 studies, 215
participants: MD -9.93 mmol/L, 95% CI -19.96 to 0.11). There were four cases of
graft loss in the normal saline group and one in the balanced electrolyte
solution group, and four cases of acute rejection in the normal saline group
compared to two cases in the balanced electrolyte solution group. AUTHORS'
CONCLUSIONS: Balanced electrolyte solutions are associated with less
hyperchloraemic metabolic acidosis compared to normal saline, however it remains
uncertain whether lower-chloride solutions lead to improved graft outcomes
compared to normal saline.
PMID- 27502171
TI - Targeted and untargeted profiling of alkaloids in herbal extracts using online
solid-phase extraction and high-resolution mass spectrometry (Q-Orbitrap).
AB - The biological activity of alkaloids (ALKs) and the different content of these
natural products in herbs and plants have made them an attractive field for
chemical studies. A screening method automatically combining online solid-phase
purification and concentration of samples with analysis using ultra-high
performance liquid chromatography coupled with a hybrid quadrupole orbitrap mass
spectrometer was developed and is reported in this paper. The proposed
quantification method was validated for 35 ALKs with reference to pure analytical
standards. A further 48 ALKs were identified on the basis of their accurate mass
and characterised for chromatographic retention time and fragmentation profile,
following their confirmation in extracts of herbs already well documented in the
literature. More than 250 other untargeted ALKs were also tentatively identified
using literature information, such as exact mass and isotopic pattern. The mass
spectrometer operated in positive ion mode and mass spectra were acquired, with
full MS-data-dependent MS/MS analysis (full MS-dd MS/MS) at a resolution of 140
000. The method was linear up to an ALK concentration of 1000/3000 ug l(-1) ,
with R(2) always >0.99 and limits of detection ranging between 0.04 and 10 ug l(
1) . Accuracy, expressed as the recovery relative error, had a median value of
7.4%, and precision (relative standard deviation %) was generally lower than 10%
throughout the quantitation range. The proposed method was then used to
investigate the targeted and untargeted ALK profile of a selection of 18 alpine
herbal plants, establishing that pyrrolizidine, pyrrolidine and piperidine ALKs
were the most well represented. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27502172
TI - Fibpredictor: a computational method for rapid prediction of amyloid fibril
structures.
AB - Amyloid fibrils are important in diseases such as Alzheimer's disease and
Parkinson's disease, and are also a common instability in peptide and protein
drug products. Despite their importance, experimental structures of amyloid
fibrils in atomistic detail are rare. To address this limitation, we have
developed a novel, rapid computational method to predict amyloid fibril
structures (Fibpredictor). The method combines beta-sheet model building, beta
sheet replication, and symmetry operations with side-chain prediction and
statistical scoring functions. When applied to nine amyloid fibrils with
experimentally determined structures, the method predicted the correct structures
of amyloid fibrils and enriched those among the top-ranked structures. These
models can be used as the initial heuristic structures for more complicated
computational studies. Fibpredictor is available at
http://nanohub.org/resources/fibpredictor .
PMID- 27502173
TI - Biliary Polyunsaturated Fatty Acids and Telocytes in Gallstone Disease.
AB - It has been reported that intake of omega-3 polyunsaturated fatty acids (PUFAs)
reduces the risk of coronary heart disease. It also influences bile composition,
decreasing biliary cholesterol saturation in the bile of patients with
gallstones. In addition to bile composition disturbances, gallbladder
hypomotility must be a cofactor in the pathogenesis of cholelithiasis, as it
leads to the prolonged nucleation phase. Our current knowledge about gallbladder
motility has been enhanced by the study of a population of newly described
interstitial (stromal) cells-telocytes (TCs). The purpose of this study was to
determine whether TC loss, reported by our team recently, might be related to
bile lithogenicity, expressed as cholesterol saturation index or the difference
in biliary PUFA profiles in patients who suffer from cholecystolithiasis and
those not affected by this disease. We determined biliary lipid composition
including the fatty acid composition of the phospholipid species in bile. Thus,
we investigated whether differences in biliary fatty acid profiles (omega-3 PUFA
and omega-6 PUFA) in gallbladder bile may influence its lithogenicity and the
quantity of TCs within the gallbladder wall. We conclude that the altered PUFA
concentrations in the gallbladder bile, with elevation of omega-6 PUFA,
constitute important factors influencing TC density in the gallbladder wall,
being one of the possible pathophysiological components for the gallstone disease
development. This study established that altered bile composition in patients
with cholelithiasis may influence TC quantity within the gallbladder muscle, and
we concluded that reduction in TC number may be a consequence of the
supersaturated bile toxicity, while some other bile components (omega-3 PUFA,
glycocholic, and taurocholic acids) may exert protective effects on TC and thus
possibly influence the mechanisms regulating gallbladder and extrahepatic bile
duct motility. Thus, omega-3 PUFA may represent a possible option to prevent
formation of cholesterol gallstones.
PMID- 27502174
TI - Marseillevirus in lymphoma: a giant in the lymph node.
AB - The family Marseilleviridae is a new clade of giant viruses whose original
member, marseillevirus, was described in 2009. These viruses were isolated using
Acanthamoeba spp primarily from the environment. Subsequently, a close relative
of marseillevirus was isolated from the faeces of a healthy young man, and others
were detected in blood samples of blood donors and recipients and in a child with
lymph node adenitis. In this Grand Round we describe the detection of
marseillevirus by PCR, fluorescence in-situ hybridisation, direct
immunofluorescence, and immunohistochemistry in the lymph node of a 30-year-old
woman diagnosed with Hodgkin's lymphoma, together with IgG antibodies to
marseillevirus. A link with viruses and bacteria has been reported for many
lymphomas. We review the literature describing these associations, the criteria
used to consider a causal association, and the underlying mechanisms of
lymphomagenesis. Our observations suggest that consideration should be given to
marseillevirus infections as an additional viral cause or consequence of
Hodgkin's lymphoma, and that this hypothesis should be tested further.
PMID- 27502175
TI - Thalassiella azotovora gen. nov., sp. nov., a New Member of the Family
Kineosporiaceae Isolated from Sea Water in South Korea.
AB - A gram-positive, nonmotile, rod-shaped, nonflagellated, aerobic bacterium,
designated strain DSD2(T) was isolated from a seawater sample from Sadong wharf,
Ulleung-Island, South Korea. Strain DSD2(T) was found to be able to grow at pH
ranging from 6 to 11 (optimum 7-8), 0-7 % (w/v) NaCl (optimum 0 %), at 10-42
degrees C (optimum 37 degrees C). 16S rRNA gene sequence analysis revealed that
strain DSD2(T) was 95.8 % similar to the type strain of Kineosporia rhamnosa KACC
15195(T), 95.8 % similar to Angustibacter aerolatus KACC 15527(T), and 95.5 %
similar to Kineococcus xinjiangensis KCTC 19474(T) as its closest relatives. A
neighbor-joining phylogenetic tree based on the 16S rRNA gene sequence showed
that strain DSD2(T) related to Micrococcineae and Kineosporiineae suborder clade.
The major polar lipids were phosphoglycolipids and phospholipids. Strain DSD2(T)
was found to contain MK-8 (H2) and MK-9 (H4) as the predominant menaquinone and
iso-C16:0 as the major fatty acid. The isolate contained meso-diaminopimelic acid
(meso-A2pm) with alanine, glutamic acid, and glycine as the diagnostic diamino
acid. The DNA G+C content of strain DSD2(T) was 73.2 mol%. On the basis of
phylogenetic, biochemical, chemotaxonomic, and other physiological
characteristics, strain DSD2(T) is assigned to a novel species of a novel genus
within the suborder Kineosporiineae and the name Thalassiella azotovora gen nov.,
sp. nov., is proposed. The type strain is DSD2(T) (= KCTC 39634(T) = JCM
31134(T)).
PMID- 27502176
TI - Magnesium-Calcite Crystal Formation Mediated by the Thermophilic Bacterium
Geobacillus thermoglucosidasius Requires Calcium and Endospores.
AB - Fresh Geobacillus thermoglucosidasius cells grown on soybean-casein digest
nutrient agar were inoculated as a parent colony 1 cm in diameter on the surface
of an agar gel containing acetate and calcium ions (calcite-promoting hydrogel)
and incubated at 60 degrees C for 4 days, after which magnesium-calcite single
crystals of 50-130 um in size formed within the parent colony. Addition of EDTA,
polyacrylic acid or N,N-dicyclohexylcarbodiimide to the calcite-forming hydrogel
inhibited the parent colony from forming magnesium-calcite crystals. Inoculation
of G. thermoglucosidasius on calcite-forming hydrogel containing 5 uM cadmium and
20 uM zinc resulted in a decrease in the sporulation rate from 55 to 7-8 %.
Magnesium-calcite synthesis decreased relative to the sporulation rate. G.
thermoglucosidasius exhibited higher adsorption/absorbance of calcium than other
Geobacillus sp. that do not mediate calcite formation and higher levels of
magnesium accumulation. Calcium ions contained in the calcite-promoting hydrogel
and magnesium ions concentrated in G. thermoglucosidasius cells serve as the
elements for magnesium-calcite synthesis. The observed decreases in sporulation
rate and magnesium-calcite formation support the hypothesis that endospores act
as nuclei for the synthesis of magnesium-calcite single crystals.
PMID- 27502177
TI - Homogenised daily lake surface water temperature data generated from multiple
satellite sensors: A long-term case study of a large sub-Alpine lake.
AB - Availability of remotely sensed multi-spectral images since the 1980's, which
cover three decades of voluminous data could help researchers to study the
changing dynamics of bio-physical characteristics of land and water. In this
study, we introduce a new methodology to develop homogenised Lake Surface Water
Temperature (LSWT) from multiple polar orbiting satellites. Precisely, we
developed homogenised 1 km daily LSWT maps covering the last 30 years (1986 to
2015) combining data from 13 satellites. We used a split-window technique to
derive LSWT from brightness temperatures and a modified diurnal temperature cycle
model to homogenise data which were acquired between 8:00 to 17:00 UTC. Gaps in
the temporal LSWT data due to the presence of clouds were filled by applying
Harmonic ANalysis of Time Series (HANTS). The satellite derived LSWT maps were
validated based on long-term monthly in-situ bulk temperature measurements in
Lake Garda, the largest lake in Italy. We found the satellite derived homogenised
LSWT being significantly correlated to in-situ data. The new LSWT time series
showed a significant annual rate of increase of 0.020 degrees C yr(-1) (*P <
0.05), and of 0.036 degrees C yr(-1) (***P < 0.001) during summer.
PMID- 27502178
TI - Nanometal Skin of Plasmonic Heterostructures for Highly Efficient Near-Field
Scattering Probes.
AB - In this work, atomic force microscopy probes are functionalized by virtue of self
assembling monolayers of block copolymer (BCP) micelles loaded either with
clusters of silver nanoparticles or bimetallic heterostructures consisting of
mixed species of silver and gold nanoparticles. The resulting self-organized
patterns allow coating the tips with a sort of nanometal skin made of
geometrically confined nanoislands. This approach favors the reproducible
engineering and tuning of the plasmonic properties of the resulting structured
tip by varying the nanometal loading of the micelles. The newly conceived tips
are applied for experiments of tip-enhanced Raman scattering (TERS) spectroscopy
and scattering-type scanning near-field optical microscopy (s-SNOM). TERS and s
SNOM probe characterizations on several standard Raman analytes and patterned
nanostructures demonstrate excellent enhancement factor with the possibility of
fast scanning and spatial resolution <12 nm. In fact, each metal nanoisland
consists of a multiscale heterostructure that favors large scattering and near
field amplification. Then, we verify the tips to allow challenging nongap-TER
spectroscopy on thick biosamples. Our approach introduces a synergistic chemical
functionalization of the tips for versatile inclusion and delivery of plasmonic
nanoparticles at the tip apex, which may promote the tuning of the plasmonic
properties, a large enhancement, and the possibility of adding new degrees of
freedom for tip functionalization.
PMID- 27502179
TI - The genetics of an early Neolithic pastoralist from the Zagros, Iran.
AB - The agricultural transition profoundly changed human societies. We sequenced and
analysed the first genome (1.39x) of an early Neolithic woman from Ganj Dareh, in
the Zagros Mountains of Iran, a site with early evidence for an economy based on
goat herding, ca. 10,000 BP. We show that Western Iran was inhabited by a
population genetically most similar to hunter-gatherers from the Caucasus, but
distinct from the Neolithic Anatolian people who later brought food production
into Europe. The inhabitants of Ganj Dareh made little direct genetic
contribution to modern European populations, suggesting those of the Central
Zagros were somewhat isolated from other populations of the Fertile Crescent.
Runs of homozygosity are of a similar length to those from Neolithic farmers, and
shorter than those of Caucasus and Western Hunter-Gatherers, suggesting that the
inhabitants of Ganj Dareh did not undergo the large population bottleneck
suffered by their northern neighbours. While some degree of cultural diffusion
between Anatolia, Western Iran and other neighbouring regions is possible, the
genetic dissimilarity between early Anatolian farmers and the inhabitants of Ganj
Dareh supports a model in which Neolithic societies in these areas were distinct.
PMID- 27502182
TI - Plasma cell cheilitis successfully treated with topical calcineurin inhibitors.
PMID- 27502180
TI - Imaging-genomics reveals driving pathways of MRI derived volumetric tumor
phenotype features in Glioblastoma.
AB - BACKGROUND: Glioblastoma (GBM) tumors exhibit strong phenotypic differences that
can be quantified using magnetic resonance imaging (MRI), but the underlying
biological drivers of these imaging phenotypes remain largely unknown. An Imaging
Genomics analysis was performed to reveal the mechanistic associations between
MRI derived quantitative volumetric tumor phenotype features and molecular
pathways. METHODS: One hundred fourty one patients with presurgery MRI and
survival data were included in our analysis. Volumetric features were defined,
including the necrotic core (NE), contrast-enhancement (CE), abnormal tumor
volume assessed by post-contrast T1w (tumor bulk or TB), tumor-associated edema
based on T2-FLAIR (ED), and total tumor volume (TV), as well as ratios of these
tumor components. Based on gene expression where available (n = 91), pathway
associations were assessed using a preranked gene set enrichment analysis. These
results were put into context of molecular subtypes in GBM and prognostication.
RESULTS: Volumetric features were significantly associated with diverse sets of
biological processes (FDR < 0.05). While NE and TB were enriched for immune
response pathways and apoptosis, CE was associated with signal transduction and
protein folding processes. ED was mainly enriched for homeostasis and cell
cycling pathways. ED was also the strongest predictor of molecular GBM subtypes
(AUC = 0.61). CE was the strongest predictor of overall survival (C-index = 0.6;
Noether test, p = 4x10(-4)). CONCLUSION: GBM volumetric features extracted from
MRI are significantly enriched for information about the biological state of a
tumor that impacts patient outcomes. Clinical decision-support systems could
exploit this information to develop personalized treatment strategies on the
basis of noninvasive imaging.
PMID- 27502183
TI - Assessment of physico-chemical characteristics of water in Tamilnadu.
AB - Water is an important component to human life. The major aims of the present work
are to assess the quality of the ground water and its impact in Villupuram
District of Tamilnadu. The present study focus to bring an awareness among the
people about the quality of ground water by taking water samples from various
locations for Physico - Chemical analysis of the ground water. This analysis
result was compared with the WHO, ICMR, USPH and European standards of drinking
water quality parameters with the following water quality parameters namely pH,
Electrical conductivity, Cl, , Na, K, Ca , Mg, Total dissolved solids, Total
hardness, Dissolved oxygen, Fluoride etc. Various chemical methods have been
employed to investigate the extent level of pollution in ground water.
PMID- 27502184
TI - Translating an early childhood obesity prevention program for local community
implementation: a case study of the Melbourne InFANT Program.
AB - BACKGROUND: While there is a growing interest in the field of research
translation, there are few published examples of public health interventions that
have been effectively scaled up and implemented in the community. This paper
provides a case study of the community-wide implementation of the Melbourne
Infant, Feeding, Activity and Nutrition Trial (InFANT), an obesity prevention
program for parents with infants aged 3-18 months. The study explored key factors
influencing the translation of the Program into routine practice and the
respective role of policy makers, researchers and implementers. METHODS: Case
studies were conducted of five of the eight prevention areas in Victoria,
Australia who implemented the Program. Cases were selected on the basis of having
implemented the Program for 6 months or more. Data were collected from January to
June 2015 and included 18 individual interviews, one focus group and observation
of two meetings. A total of 28 individuals, including research staff (n = 4),
policy makers (n = 2) and implementers (n = 22), contributed to the data
collected. Thematic analysis was conducted using cross case comparisons and key
themes were verified through member checking. RESULTS: Key facilitators of
implementation included availability of a pre-packaged evidence based program
addressing a community need, along with support and training provided by research
staff to local implementers. Partnerships between researchers and policy makers
facilitated initial program adoption, while local partnerships supported
community implementation. Community partnerships were facilitated by local
coordinators through alignment of program goals with existing policies and
services. Workforce capacity for program delivery and administration was a
challenge, largely overcome by embedding the Program into existing roles.
Adapting the Program to fit local circumstance was critical for feasible and
sustainable delivery, however balancing this with program fidelity was a critical
issue. The lack of ongoing funding to support translation activities was a
barrier for researchers continued involvement in community implementation.
CONCLUSION: Policy makers, researchers and practitioners have important and
complementary roles to play in supporting the translation of effective research
interventions into practice. New avenues need to be explored to strengthen
partnerships between researchers and end users to support the integration of
effective public health research interventions into practice.
PMID- 27502185
TI - The superior fault tolerance of artificial neural network training with a
fault/noise injection-based genetic algorithm.
AB - Artificial neural networks (ANNs) are powerful computational tools that are
designed to replicate the human brain and adopted to solve a variety of problems
in many different fields. Fault tolerance (FT), an important property of ANNs,
ensures their reliability when significant portions of a network are lost. In
this paper, a fault/noise injection-based (FIB) genetic algorithm (GA) is
proposed to construct fault-tolerant ANNs. The FT performance of an FIB-GA was
compared with that of a common genetic algorithm, the back-propagation algorithm,
and the modification of weights algorithm. The FIB-GA showed a slower fitting
speed when solving the exclusive OR (XOR) problem and the overlapping
classification problem, but it significantly reduced the errors in cases of
single or multiple faults in ANN weights or nodes. Further analysis revealed that
the fit weights showed no correlation with the fitting errors in the ANNs
constructed with the FIB-GA, suggesting a relatively even distribution of the
various fitting parameters. In contrast, the output weights in the training of
ANNs implemented with the use the other three algorithms demonstrated a positive
correlation with the errors. Our findings therefore indicate that a combination
of the fault/noise injection-based method and a GA is capable of introducing FT
to ANNs and imply that the distributed ANNs demonstrate superior FT performance.
PMID- 27502186
TI - On the ground in Western Africa: from the outbreak to the elapse of Ebola.
PMID- 27502187
TI - The emerging roles of the DDX41 protein in immunity and diseases.
AB - RNA helicases are involved in almost every aspect of RNA, from transcription to
RNA decay. DExD/H-box helicases comprise the largest SF2 helicase superfamily,
which are characterized by two conserved RecA-like domains. In recent years, an
increasing number of unexpected functions of these proteins have been discovered.
They play important roles not only in innate immune response but also in diseases
like cancers and chronic hepatitis C. In this review, we summarize the recent
literatures on one member of the SF2 superfamily, the DEAD-box protein DDX41.
After bacterial or viral infection, DNA or cyclic-di-GMP is released to cells.
After phosphorylation of Tyr414 by BTK kinase, DDX41 will act as a sensor to
recognize the invaders, followed by induction of type I interferons (IFN). After
the immune response, DDX41 is degraded by the E3 ligase TRIM21, using Lys9 and
Lys115 of DDX41 as the ubiquitination sites. Besides the roles in innate
immunity, DDX41 is also related to diseases. An increasing number of both
inherited and acquired mutations in DDX41 gene are identified from
myelodysplastic syndrome and/or acute myeloid leukemia (MDS/AML) patients. The
review focuses on DDX41, as well as its homolog Abstrakt in Drosophila, which is
important for survival at all stages throughout the life cycle of the fly.
PMID- 27502188
TI - Rab1A mediates proinsulin to insulin conversion in beta-cells by maintaining
Golgi stability through interactions with golgin-84.
PMID- 27502189
TI - Dual red imaging (novel advanced endoscopy) can increase visibility and can
predict the depth in diagnosing esophageal varices.
AB - BACKGROUND: Dual red imaging (DRI) is a new technology that can increase the
visibility of deeper veins compared with narrow band imaging (NBI). As esophageal
varices (EVs) are a vascular disease occurring in the submucosal layer, their
visibility might be increased by DRI. We prospectively clarified whether the
visibility of EVs with red color sign (RCS) can be increased by DRI, and
clarified the relation between the visibility scores and the obtained endoscopic
ultrasound (EUS) images. METHODS: Forty patients were enrolled. The visibility of
the EVs on DRI and NBI endoscopic images was evaluated by five observers in a
blinded manner and was compared with a white light image (bad, 0; equal, 1; good,
2). The diameter of the lumen and the depth of the EVs and RCS from the
epithelium were measured by EUS. The relation between the visibility scores and
the EUS findings was investigated. RESULTS: The DRI scores were 1.66 +/- 0.34 for
the EV substance and 1.79 +/- 0.28 for the RCS, whereas the NBI scores were 0.68
+/- 0.38 and 0.41 +/- 0.28, respectively. A significant negative correlation was
found between the depth and the visibility score (r = -0.505, p = 0.001 for EVs;
r = -0.458, p = 0.003 for RCS). CONCLUSIONS: DRI increased the visibility of the
EVs and RCS. The visibility of the EVs or RCS in the shallower position was more
enhanced by DRI. Visual recognition of the changing degrees of visibility by DRI
enables the prediction of the depth of EVs.
PMID- 27502190
TI - AvaR2, a pseudo gamma-butyrolactone receptor homologue from Streptomyces
avermitilis, is a pleiotropic repressor of avermectin and avenolide biosynthesis
and cell growth.
AB - Avermectins produced by Streptomyces avermitilis are effective anthelmintic
agents. The autoregulatory signalling molecule that triggers avermectin
biosynthesis is a novel butenolide-type molecule, avenolide, rather than common
gamma-butyrolactones (GBLs). We identified AvaR2, a pseudo GBL receptor
homologue, as an important repressor of avermectin and avenolide biosynthesis and
cell growth. AvaR2 directly repressed transcription of aveR (the ave cluster
situated activator gene), aco (a key gene for avenolide biosynthesis), its own
gene (avaR2) and two other GBL receptor homologous genes (avaR1 and avaR3) by
binding to their promoter regions. The aveR promoter had the highest affinity for
AvaR2. A consensus 18 bp ARE (autoregulatory element)-like sequence was found in
the AvaR2-binding regions of these five target genes. Eleven novel AvaR2 targets
were identified, including genes involved in primary metabolism, ribosomal
protein synthesis, and stress responses. AvaR2 bound and responded to endogenous
avenolide and exogenous antibiotics jadomycin B (JadB) and aminoglycosides to
modulate its DNA-binding activity. Our findings help to clarify the roles of
pseudo GBL receptors as pleiotropic regulators and as receptors for new type
autoregulator and exogenous antibiotic signal. A pseudo GBL receptor-mediated
antibiotic signalling transduction system may be a common strategy that
facilitates Streptomyces interspecies communication and survival in complex
environments.
PMID- 27502191
TI - High-dose ustekinumab for the treatment of severe, recalcitrant pyoderma
gangrenosum.
PMID- 27502192
TI - Solvothermal Synthesis, Structure and Optical Property of Nanosized CoSb3
Skutterudite.
AB - Binary skutterudite CoSb3 nanoparticles were synthesized by solvothermal method.
The nanostructuring of CoSb3 material was achieved by the inclusion of various
kinds of additives. X-ray diffraction examination indicated the formation of the
cubic phase of CoSb3. Structural analysis by transmission electron microscopy
analysis further confirmed the formation of crystalline CoSb3 nanoparticles with
high purity. With the assistance of additives, CoSb3 nanoparticles with size as
small as 10 nm were obtained. The effect of the nanostructure of CoSb3 on the UV
visible absorption and luminescence was studied. The nanosized CoSb3 skutterudite
may find application in developing thermoelectric devices with better efficiency.
PMID- 27502193
TI - Erratum to: One-Step UV-Induced Synthesis of Polypyrrole/Ag Nanocomposites at the
Water/Ionic Liquid Interface.
PMID- 27502194
TI - An anatomical study of the orbital floor in relation to the infraorbital groove:
implications of predisposition to orbital floor fracture site.
AB - PURPOSE: To examine the anatomy of the orbital floor in relation to the
infraorbital groove. METHODS: Twenty-two Japanese cadavers aged 86.9 +/- 6.0
years at death were used. We examined whether the bony overhang on the
infraorbital nerve extending laterally was connected to the segment medial to the
infraorbital groove. The bone thicknesses at 1, 2, and 3 mm anterior to the
junction between the infraorbital groove and the inferior orbital fissure were
measured along the groove. We examined the angle between the infraorbital groove
and the orbital floor, both at the medial and lateral margins, at the thinnest
point in the above three measurement points. We used the measurement values
examined in the left orbits to prevent doubling the number of the orbits.
RESULTS: The bony overhang was not connected to the medial segment in 19 (86.4 %)
orbits. The thickness at the thinnest point was thinner in the medial portion
(1.02 +/- 1.20 mm) than in the lateral portion (2.60 +/- 1.82 mm; p = 0.001). The
angle between the medial margin and the orbital floor was obtuse (156.5 degrees
+/- 12.3 degrees ), compared with that of the lateral margin (104.0 degrees +/-
17.0 degrees ; p < 0.001). CONCLUSIONS: The results of this study imply that the
medial portion has an anatomical weakness and few supportive structures. Although
these findings were obtained only from Japanese cadavers, there may be associated
with frequent occurrences of an orbital floor fracture just medial to the
infraorbital groove.
PMID- 27502195
TI - Practice of ultrasound-guided central venous catheter technique by the French
intensivists: a survey from the BoReal study group.
AB - BACKGROUND: The ultrasound (US)-guided technique has been recommended for central
venous catheter (CVC) placement in critical care. However, several surveys have
shown that the majority of physicians continue to perform landmark procedures. In
our region, we have implemented special courses to promote the use of US with
formal training and simulators. Ultrasound machines have also been installed in
almost every ICU in our area. We designed a survey to investigate whether the
training program established for years and the widespread of ultrasound devices
in the ICU of our region will be associated with a high rate of physicians
performing US procedures. METHODS: A survey comprising 14 questions was designed
to elicit information on training in US techniques, the use of US for CVC
placement, reasons for nonuse of US and their opinion concerning the need to
teach the landmark technique to residents. This survey was electronically sent to
every physician of the BoReal study group (32 ICUs located in the North West of
France). RESULTS: We received 190 responses (response rate 66 %) including 34 %
of residents. Only 11 % of respondents reported the absence of training in the US
technique, and 3 % reported they did not have access to an ultrasound machine. A
total of 68 % declared "always" (18 %) or "almost always" (50 %) using US to
guide CVC placement. Our results are better than those of previous surveys. The
main reasons why physicians did not use the US technique were that they thought
that US guidance was unnecessary (36 %) or because the ultrasound machine was not
immediately available (33 %). Ninety-one percentages think that the landmark
technique should still be taught to the residents. A higher proportion of
residents compared to seniors declared that they always or almost always used the
US technique. CONCLUSION: Training in ultrasound techniques and the widespread
availability of ultrasound machines in ICUs seem to improve the rate of US
procedures. However, despite strong scientific evidence a proportion of
physicians continue to consider the landmark technique as an alternative to US.
Training and education are potentially still the best ways to overcome such
barriers or conviction.
PMID- 27502197
TI - Women's Use of Health Care in the First 2 Years Postpartum: Occurrence and
Correlates.
AB - Objectives We sought to determine rates and correlates of accessing health care
in the 2 years following delivery among women at an urban academic medical
center. Methods We used electronic medical records, discharge, and billing data
to determine the occurrence of primary care, other non-primary outpatient care,
emergency department visits, and inpatient admissions among women delivering at a
single medical center who had a known primary care affiliation to that medical
center over a 5 year period. We explored sociodemographic, clinical, and health
care-related factors as correlates of care, using bivariate and multivariable
modeling. Results Of 6216 women studied, most (91 %) had had at least one health
care visit in the window between 2 months and 2 years postpartum (the "late
postpartum period"). The majority (81 %) had had a primary care visit. Factors
associated with use of health care in this period included a chronic medical
condition diagnosed prior to pregnancy (adjusted odds ratio (AOR) 1.42, 95 % CI
[1.19, 1.71]), prenatal care received in an urban community health center (AOR
1.35 [1.06, 1.73]), having received obstetric (AOR 1.90 [1.51, 2.37]), primary
(AOR 2.30 [1.68, 3.23]), or other non-primary outpatient care (AOR 2.35 [1.72,
3.39]) in the first 2 months postpartum, and living closer to the hospital [AOR
for residence >17.8 miles from the medical center (AOR 0.74 [0.61, 0.90])].
Having had an obstetrical complication did not increase the likelihood of receipt
of care during this window. Conclusions for Practice Among women already enrolled
in a primary care practice at our medical center, health care utilization in the
late postpartum period is high, but not universal. Understanding the
characteristics of women who return for health care during this window, and where
they are seen, can improve transitions of care across the life course and can
provide opportunities for important and consistent interconception and well-woman
messaging.
PMID- 27502196
TI - Polymyxin-B hemoperfusion in septic patients: analysis of a multicenter registry.
AB - BACKGROUND: In 2010, the EUPHAS 2 collaborative group created a registry with the
purpose of recording data from critically ill patients suffering from severe
sepsis and septic shock treated with polymyxin-B hemoperfusion (PMX-HP) for
endotoxin removal. The aim of the registry was to verify the application of PMX
HP in the daily clinical practice. METHODS: The EUPHAS 2 registry involved 57
centers between January 2010 and December 2014, collecting retrospective data of
357 patients (297 in Europe and 60 in Asia) suffering from severe sepsis and
septic shock caused by proved or suspected infection related to Gram negative
bacteria. All patients received atleast one cycle of extracorporeal endotoxin
removal by PMX-HP. RESULTS: Septic shock was diagnosed in 305 (85.4 %) patients.
The most common source of infection was abdominal (44.0 %) followed by pulmonary
(17.6 %). Gram negative bacteria represented 60.6 % of the pathogens responsible
of infection. After 72 h from the first cycle of PMX-HP, some of the SOFA score
components significantly improved with respect to baseline: cardiovascular (2.16
+/- 1.77 from 3.32 +/- 1.29, p < 0.0001), respiratory (1.95 +/- 0.95 from 2.40 +/
1.06, p < 0.001) and renal (1.84 +/- 1.77 from 2.23 +/- 1.62, p = 0.013).
Overall 28-day survival rate was 54.5 % (60.4 % in abdominal and 47.5 % in
pulmonary infection). Patients with abdominal infection treated with PMX-HP
within 24 h from the diagnosis of septic shock had a 28-day survival rate of 64.5
%. Patients showing a significantly cardiovascular improvement after PMX-HP had a
28-survival rate of 75 % in comparison to the 39 % of patients who did not (p <
0.001). Cox regression analysis found the variation of cardiovascular,
respiratory and coagulation SOFA to be independent covariates for 28-day
survival. In European patients were observed a higher 28-day (58.8 vs. 34.5 %, p
= 0.003), ICU (59 vs. 36.7 %, p = 0.006) and hospital survival rate (53.2 vs. 35
%, p = 0.02) than in Asian patients. However, the two populations were highly
heterogeneous in terms of source of infection and severity scores at admission.
CONCLUSION: The EUPHAS 2 is the largest registry conducted outside Japan on the
clinical use of PMX-HP in septic patients. Data analysis confirmed the
feasibility of PMX-HP to treat septic patients in daily clinical practice,
showing clinical benefits associated with endotoxin removal without significant
adverse events related to the extracorporeal technique.
PMID- 27502198
TI - The Ohio Gestational Diabetes Postpartum Care Learning Collaborative: Development
of a Quality Improvement Initiative to Improve Systems of Care for Women.
AB - Objectives To improve clinical practice and increase postpartum visit Type 2
diabetes mellitus (T2DM) screening rates in women with a history of gestational
diabetes mellitus (GDM). Methods We recruited clinical sites with at least half
of pregnant patients enrolled in Medicaid to participate in an 18-month quality
improvement (QI) project. To support clinical practice changes, we developed
provider and patient toolkits with educational and clinical practice resources.
Clinical subject-matter experts facilitated a learning network to train sites and
promote discussion and learning among sites. Sites submitted data from patient
chart reviews monthly for key measures that we used to provide rapid-cycle
feedback. Providers were surveyed at completion regarding toolkit usefulness and
satisfaction. Results Of fifteen practices recruited, twelve remained actively
engaged. We disseminated more than 70 provider and 2345 patient toolkits.
Documented delivery of patient education improved for timely GDM prenatal
screening, reduction of future T2DM risk, smoking cessation, and family planning.
Sites reported toolkits were useful and easy to use. Of women for whom postpartum
data were available, 67 % had a documented postpartum visit and 33 % had a
postpartum T2DM screen. Lack of information sharing between prenatal and
postpartum care providers was are barriers to provision and documentation of
care. Conclusions for Practice QI and toolkit resources may improve the quality
of prenatal education. However, postpartum care did not reach optimal levels.
Future work should focus on strategies to support coordination of care between
obstetrical and primary care providers.
PMID- 27502199
TI - Advancing MCH Interdisciplinary/Interprofessional Leadership Training and
Practice Through a Learning Collaborative.
AB - Purpose The Interdisciplinary Leadership Learning Collaborative (ILLC), under the
sponsorship of AUCD and the Maternal and Child Health Bureau, brought together
six teams, composed of 14 MCHB and UCEDD training programs to enhance their
leadership training. Description Using adult learning principles, interactive
training methods, and skill-focused learning, the ILLC built upon the evidence
based Interdisciplinary Leadership Development Program of the University of North
Carolina at Chapel Hill. The program began with a 4-day on-site intensive and
then continued through monthly conference calls, a mid-term on-site workshop, and
a summary virtual workshop to present programmatic accomplishments and share
plans for sustainability. Coaching/consultation for the teams around particular
challenges was also part of the program. Assessment All teams reported
enhancements in intentional leadership training, threading of leadership concepts
across clinical, didactic, and workshop settings, and new collaborative
partnerships for leadership training. Teams also identified a number of
strategies to increase sustainability of their intentional leadership training
efforts. Conclusion for Practice The learning collaborative is a productive model
to address the growing need for interdisciplinary MCH leaders.
PMID- 27502200
TI - A rapid marker ordering approach for high-density genetic linkage maps in
experimental autotetraploid populations using multidimensional scaling.
AB - KEY MESSAGE: The paper proposes and validates a robust method for rapid
construction of high-density linkage maps suitable for autotetraploid species.
Modern genotyping techniques are producing increasingly high numbers of genetic
markers that can be scored in experimental populations of plants and animals.
Ordering these markers to form a reliable linkage map is computationally
challenging. There is a wide literature on this topic, but most has focussed on
populations derived from diploid, homozygous parents. The challenge of ordering
markers in an autotetraploid population has received little attention, and there
is currently no method that runs sufficiently rapidly to investigate the effects
of omitting problematic markers on map order in larger datasets. Here, we have
explored the use of multidimensional scaling (MDS) to order markers from a cross
between autotetraploid parents, using simulated data with 74-152 markers on a
linkage group and also experimental data from a potato population. We compared
different functions of the recombination fraction and LOD score to form the MDS
stress function and found that an LOD2 weighting generally performed well,
including when missing values and genotyping errors are present. We conclude that
an initial analysis using unconstrained MDS gives a rapid method to detect and
remove problematic markers, and that a subsequent analysis using either
constrained MDS or principal curve analysis gives reliable marker orders. The
latter approach is also particularly rapid, taking less than 10 s on a set of 258
markers compared to 6 days for the JoinMap software. This MDS approach could also
be applied to experimental populations of diploid species.
PMID- 27502201
TI - Stigma and Mental Health: A Proposal for Next Steps.
PMID- 27502202
TI - Comparison of chemical compositions in air particulate matter during summer and
winter in Beijing, China.
AB - The development of industry in Beijing, the capital of China, particularly in
last decades, has caused severe environmental pollution including particulate
matter (PM), dust-haze, and photochemical smog, which has already caused
considerable harm to local ecological environment. Thus, in this study, air
particle samples were continuously collected in August and December, 2014. And
elements (Si, Al, V, Cr, Mn, Fe, Ni, Cu, Zn, Mo, Cd, Ba, Pb and Ti) and ions
([Formula: see text], [Formula: see text], F-, Cl-, Na+, K+, Mg2+, Ca2+ and
[Formula: see text]) were analyzed by inductively coupled plasma mass
spectrometer and ion chromatography. According to seasonal changes, discuss the
various pollution situations in order to find possible particulate matter sources
and then propose appropriate control strategies to local government. The results
indicated serious PM and metallic pollution in some sampling days, especially in
December. Chemical Mass Balance model revealed central heating activities, road
dust and vehicles contribute as main sources, account for 5.84-32.05 %
differently to the summer and winter air pollution in 2014.
PMID- 27502203
TI - Aboveground Epichloe coenophiala-Grass Associations Do Not Affect Belowground
Fungal Symbionts or Associated Plant, Soil Parameters.
AB - Cool season grasses host multiple fungal symbionts, such as aboveground Epichloe
endophytes and belowground arbuscular mycorrhizal fungi (AMF) and dark septate
endophytes (DSEs). Asexual Epichloe endophytes can influence root colonization by
AMF, but the type of interaction-whether antagonistic or beneficial-varies. In
Schedonorus arundinaceus (tall fescue), Epichloe coenophiala can negatively
affect AMF, which may impact soil properties and ecosystem function. Within field
plots of S. arundinaceus that were either E. coenophiala-free (E-), infected with
the common, mammal-toxic E. coenophiala strain (CTE+), or infected with one of
two novel, non-toxic strains (AR542 NTE+ and AR584 NTE+), we hypothesized that
(1) CTE+ would decrease AMF and DSE colonization rates and reduce soil
extraradical AMF hyphae compared to E- or NTE+, and (2) this would lead to E- and
NTE+ plots having greater water stable soil aggregates and C than CTE+. E.
coenophiala presence and strain did not significantly alter AMF or DSE
colonization, nor did it affect extraradical AMF hypha length, soil aggregates,
or aggregate-associated C and N. Soil extraradical AMF hypha length negatively
correlated with root AMF colonization. Our results contrast with previous
demonstrations that E. coenophiala symbiosis inhibits belowground AMF
communities. In our mesic, relatively nutrient-rich grassland, E. coenophiala
symbiosis did not antagonize belowground symbionts, regardless of strain.
Manipulating E. coenophiala strains within S. arundinaceus may not significantly
alter AMF communities and nutrient cycling, yet we must further explore these
relationships under different soils and environmental conditions given that
symbiont interactions can be important in determining ecosystem response to
global change.
PMID- 27502204
TI - Obstructive sleep apnea is associated with visit-to-visit variability in low
density lipoprotein-cholesterol in patients with coronary artery disease.
AB - PURPOSE: Visit-to-visit variability in low-density lipoprotein-cholesterol (LDL
C) was found to be a novel predictor of adverse cardiac events. Obstructive sleep
apnea (OSA), an emerging cardiovascular risk factor, is characterized by
sympathetic activation and increased oxidative stress which are regulators of LDL
C metabolism. We hypothesized that OSA was associated with LDL-C variability.
METHODS: We prospectively recruited 190 patients with coronary artery disease for
an overnight sleep study. Statin was prescribed upon discharge for 186 patients.
Serum LDL-C levels were measured at clinic every 3 to 6 months. Severity of OSA
(on the basis of apnea-hypopnea index (AHI)) was correlated with visit-to-visit
LDL-C variability (on the basis of variation independent of mean (VIM)) in
outpatient clinic. RESULTS: The mean AHI was 21.9 +/- 18.9. Using an AHI cut-off
of 5-14.9, 15-29.9, and >=30, the prevalence of mild, moderate, and severe OSA
was 26.3, 18.9, and 27.4 %, respectively. After 53.2 +/- 25.3 months, LDL-C was
recorded over 8.1 +/- 4.2 measurements. VIM positively correlated with AHI
(Pearson's r = 0.183, p = 0.016), but not body mass index, baseline and mean
follow-up LDL-C levels, and number of LDL-C measurements. In multiple linear
regression analysis, AHI remained an independent predictor of VIM after adjusting
for diabetes mellitus and hyperlipidemia. A 10-unit rise in AHI led to a 3.8 %
increase in VIM (95 % CI 0.1 to 7.4 %; p = 0.044). CONCLUSION: This is the first
study to show the independent correlation between OSA severity and visit-to-visit
LDL-C variability. Our finding contributes to the understanding of the
vasculopathic effects of OSA.
PMID- 27502205
TI - Meta-analysis of all-cause and cardiovascular mortality in obstructive sleep
apnea with or without continuous positive airway pressure treatment.
AB - PURPOSE: The associations between obstructive sleep apnea (OSA) and all-cause and
cardiovascular mortality are well established but are not entirely consistent. To
accurately evaluate these associations as well as the therapeutic effects of
continuous positive airway pressure (CPAP), we conducted a comprehensive meta
analysis of all eligible cohort studies. METHODS: Electronic literature databases
(i.e., PubMed and Embase) were searched for relevant studies published before
January 2016 that evaluated the associations between OSA and all-cause or
cardiovascular mortality. Random-effect models were used to calculate the pooled
hazard ratio (HR) and corresponding 95 % confidence intervals (CIs) for
categorical risk estimates. The therapeutic effects of CPAP treatment for all
cause and cardiovascular mortality in OSA were examined through the meta
analysis. RESULTS: The 27 cohort studies included in the meta-analysis included
3,162,083 participants. Compared to the control group, the pooled HR of all-cause
mortality was 1.19 (95 % CI, 0.86-1.65) for mild OSA, 1.28 (0.96-1.69) for
moderate OSA, and 2.13 (1.68-2.68) for severe OSA. The pooled HR of
cardiovascular mortality was 1.24 (0.53-2.55) for mild OSA, 2.05 (0.57-5.47) for
moderate OSA, and 2.73 (1.94-3.85) for severe OSA. All-cause mortality (HR 0.66;
0.59-0.73) and cardiovascular mortality (HR 0.37; 0.16-0.54) were significantly
lower in CPAP-treated than in untreated patients. There were no differences in
cardiovascular mortality in CPAP-treated OSA patients vs. normal control subjects
(HR 0.82; 0.52-1.29). CONCLUSIONS: Greater attention should be paid to severe
OSA, as it is an independent predictor for risk for all-cause and cardiovascular
mortality. CPAP is an effective treatment that reduces risk of mortality.
PMID- 27502206
TI - Microbial functional genes enriched in the Xiangjiang River sediments with heavy
metal contamination.
AB - BACKGROUND: Xiangjiang River (Hunan, China) has been contaminated with heavy
metal for several decades by surrounding factories. However, little is known
about the influence of a gradient of heavy metal contamination on the diversity,
structure of microbial functional gene in sediment. To deeply understand the
impact of heavy metal contamination on microbial community, a comprehensive
functional gene array (GeoChip 5.0) has been used to study the functional genes
structure, composition, diversity and metabolic potential of microbial community
from three heavy metal polluted sites of Xiangjiang River. RESULTS: A total of
25595 functional genes involved in different biogeochemical processes have been
detected in three sites, and different diversities and structures of microbial
functional genes were observed. The analysis of gene overlapping, unique genes,
and various diversity indices indicated a significant correlation between the
level of heavy metal contamination and the functional diversity. Plentiful
resistant genes related to various metal were detected, such as copper, arsenic,
chromium and mercury. The results indicated a significantly higher abundance of
genes involved in metal resistance including sulfate reduction genes (dsr) in
studied site with most serious heavy metal contamination, such as cueo, mer,
metc, merb, tehb and terc gene. With regard to the relationship between the
environmental variables and microbial functional structure, S, Cu, Cd, Hg and Cr
were the dominating factor shaping the microbial distribution pattern in three
sites. CONCLUSIONS: This study suggests that high level of heavy metal
contamination resulted in higher functional diversity and the abundance of metal
resistant genes. These variation therefore significantly contribute to the
resistance, resilience and stability of the microbial community subjected to the
gradient of heavy metals contaminant in Xiangjiang River.
PMID- 27502207
TI - Amelotin gene expression is temporarily being upregulated at the initiation of
apoptosis induced by TGFbeta1 in mouse gingival epithelial cells.
AB - Amelotin (AMTN) is expressed and secreted by ameloblasts in the maturation stage
of amelogenesis and persist with low levels in the junctional epithelium (JE) of
erupted teeth. The purpose of this study is to investigate the transcriptional
regulation of the AMTN gene by transforming growth factor beta1 (TGFbeta1) in
gingival epithelial (GE1) cells in the apoptosis phase. Apoptosis was evaluated
by the fragmentation of chromosomal DNA and TUNEL staining. A real-time PCR was
carried out to examine the AMTN mRNA levels induced by TGFbeta1 and Smad3
overexpression. Transient transfection analyses were completed using the various
lengths of mouse AMTN gene promoter constructs with or without TGFbeta1.
Chromatin immunoprecipitation (ChIP) assays were performed to investigate the
Smad3 bindings to the AMTN gene promoter by TGFbeta1. TGFbeta1-induced apoptosis
in GE1 cells were detected at 24 and 48 h by DNA fragmentation and TUNEL
staining. AMTN mRNA levels increased at 6 h and reached maximum at 24 h in GE1
cells. Luciferase activities of the mouse AMTN gene promoter constructs were
induced by TGFbeta1. The results of the ChIP assays showed that there was an
increase in Smad3 binding to Smad-binding element (SBE)#1 and SBE#2 after
stimulation by TGFbeta1. Immunohistochemical localization of AMTN was detected in
the JE, and the AMTN protein levels in Smad3-deficient mice were decreased
compared with wild-type mice. AMTN mRNA levels were induced at the initiation of
apoptosis by TGFbeta1, which mediated through the Smad3 bindings to SBEs in the
mouse AMTN gene promoter.
PMID- 27502208
TI - Novel SAHA analogues inhibit HDACs, induce apoptosis and modulate the expression
of microRNAs in hepatocellular carcinoma.
AB - In eukaryotes, transcriptional regulation occurs via chromatin remodeling, mainly
through post translational modifications of histones that package DNA into
structural units. Histone deacetylases (HDACs) are enzymes that play important
role in various biological processes by repressing gene expression.
Suberoylanilide hydroxamic acid (SAHA) is a known HDAC inhibitor that showed
significant anti cancer activity by relieving gene silencing against hematologic
and solid tumors. We have designed and synthesized a series of SAHA analogs C1-C4
and performed biological studies to elucidate its anti-cancer effects. It is
observed that SAHA analogs significantly inhibited cell proliferation and induced
apoptosis in hepatocellular carcinoma (HCC) cell lines HepG2 and SK-HEP-1. These
analogs also showed non-toxic activity towards primary human hepatocytes, which
describes its tumor specificity. SAHA analogs exhibited strong HDAC inhibition,
which is 2-3 fold higher compared to SAHA. Moreover, these molecules induced
hyper acetylation of histone H3 at various positions on the lysine residue.
Further, it is observed that SAHA analogs are strong inducers of apoptosis, as
they regulated the expression of various proteins involved in both extrinsic and
intrinsic pathways. Interestingly, SAHA analogs induced upregulation of tumor
suppressor miRNAs by activating its biogenesis pathway. Further, it is confirmed
by microRNA (miRNA) prediction tools that these miRNAs are capable of targeting
various anti-apoptotic genes. Based on these findings we conclude that SAHA
analogs could be strong HDAC inhibitors with promising apoptosis inducing nature
in HCC.
PMID- 27502209
TI - Assessing Computational Fractional Flow Reserve From Optical Coherence Tomography
in Patients With Intermediate Coronary Stenosis in the Left Anterior Descending
Artery.
AB - BACKGROUND: Intravascular optical coherence tomography (OCT) imaging provides
limited information on the functional assessment of coronary stenosis. We
evaluated a new approach to OCT image-based computation modeling, which can be
used to estimate the fractional flow reserve (FFR) in patients with intermediate
coronary stenosis. METHODS AND RESULTS: Ninety-two patients with intermediate
diameter stenosis in the left anterior descending artery underwent both FFR
measurement with pressure wires and OCT examination. Using the OCT data, a
computational fluid dynamics algorithm was used to calculate the computational
FFR (FFROCT). The diagnostic performance of the FFROCT was assessed based on the
pressure wire-based FFR. The median FFR and FFROCT values were 0.86 (0.79-0.89)
and 0.89 (0.82-0.94), respectively. The average diameter stenosis in quantitative
coronary angiography and area stenosis in OCT were 58.1+/-13.4% and 67.5+/-13.5%,
respectively. The FFROCT was better correlated to the FFR than were the anatomic
variables (r=0.72; P<0.001 versus r=0.46; P<0.001 for minimal luminal diameter on
quantitative coronary angiography or r=0.57; P<0.001 for minimal lumen area on
OCT). When functionally significant stenosis was defined as an FFR cutoff value
of <=0.8, FFROCT resulted in 88.0% accuracy, 68.7% sensitivity, and 95.6%
specificity. The positive and negative predictive values were 84.2% and 89.0%,
respectively. CONCLUSIONS: The computation of FFROCT enables assessment not only
of anatomic information, but also of the functional significance of intermediate
stenosis. This measurement may be a useful approach for the simultaneous
evaluation of the functional and anatomic severity of coronary stenosis.
PMID- 27502210
TI - Letter by Saad et al Regarding Article, "Outcomes With Intravascular Ultrasound
Guided Stent Implantation: A Meta-Analysis of Randomized Trials in the Era of
Drug-Eluting Stents".
PMID- 27502211
TI - Response by Elgendy et al to Letter Regarding Article, "Outcomes With
Intravascular Ultrasound-Guided Stent Implantation: A Meta-Analysis of Randomized
Trials in the Era of Drug-Fluting Stents".
PMID- 27502212
TI - Women in Interventional Cardiology: Small Numbers, Big Impact.
PMID- 27502213
TI - A qualitative review of implementer perceptions of the national community-level
malaria surveillance system in Southern Province, Zambia.
AB - BACKGROUND: Parts of Zambia with very low malaria parasite prevalence and high
coverage of vector control interventions are targeted for malaria elimination
through a series of interventions including reactive case detection (RCD) at
community level. When a symptomatic individual presenting to a community health
worker (CHW) or government clinic is diagnostically confirmed as an incident
malaria case an RCD response is initiated. This consists of a CHW screening the
community around the incident case with rapid diagnostic tests (RDT) and treating
positive cases with artemether-lumefantrine (AL, CoartemTM) in accordance with
national policy. Since its inception in 2011, Zambia's RCD programme has relied
on anecdotal feedback from staff to identify issues and possible solutions. In
2014, a systematic qualitative programme review was conducted to determine
perceptions around malaria rates, incentives, operational challenges and
solutions according to CHWs, their supervisors and district-level managers.
METHODS: A criterion-based sampling framework based on training regime and
performance level was used to select nine rural health posts in four districts of
Southern Province. Twenty-two staff interviews were completed to produce English
or bilingual (CiTonga or Silozi + English) verbatim transcripts, which were then
analysed using thematic framework analysis. RESULTS: CHWs, their supervisors and
district-level managers strongly credited the system with improving access to
malaria services and significantly reducing the number of cases in their area.
The main implementation barriers included access (e.g., lack of rain gear, broken
bicycles), insufficient number of CHWs for programme coverage, communication
(e.g. difficulties maintaining cell phones and "talk time" to transmit data by
phone), and inconsistent supply chain (e.g., inadequate numbers of RDT kits and
anti-malarial drugs to test and treat uncomplicated cases). CONCLUSIONS: This
review highlights the importance of a community surveillance system like RCD in
shaping Zambia's malaria elimination campaign by identifying community-based
infections that might otherwise remain undetected. At this stage the system must
ensure it can meet growing public demand by providing CHWs the tools and
materials they need to consistently carry out their work and expand programme
reach to more isolated communities. Results from this review will be used to plan
programme scale-up into other parts of Zambia.
PMID- 27502214
TI - Understanding the double burden of malnutrition in food insecure households in
Brazil.
AB - Household food insecurity (HFI) has been associated with both obesity among
mothers and undernutrition among children. However, this association has not been
well investigated in mother/child pairs living in the same household. The
objective of this study was to examine the relationship of coexistence of
maternal overweight and child stunting with HFI in Brazil. We conducted secondary
data analyses of the 2006 Brazilian National Demographic and Health Survey. We
analyzed the nutritional status of 4299 pairs of 15-49-year-olds mothers and
their children under 5 years of age. The double burden of malnutrition (DBM) was
defined as the presence of an overweight mother and a stunted child in the same
household. HFI was measured with the Brazilian HFI Measurement Scale. The
association between DBM and HFI was examined with hierarchical multivariable
logistic regression analyses. Severe HFI was associated with DBM after adjusting
for macroeconomic and household level socio-economic and demographic variables
(Adjusted OR: 2.65 - CI: 1.17-8.53). Findings suggest that policies and
programmes targeting HFI are needed to prevent the coexistence of child chronic
undernutrition and maternal overweight/obesity in the same household. These
investments are likely to be highly cost-effective as stunting has been
identified as one of the major risk factors for poor child development and adult
overweight/obesity and a strong risk factor for the development of costly chronic
diseases including type 2 diabetes and cardiovascular disease.
PMID- 27502215
TI - Spindle-cell rhabdomyosarcoma of the thumb: Rare site, rare tumor in a child.
AB - Spindle-cell rhabdomyosarcoma (RMS) is a relatively recently recognized favorable
variant of embryonal RMS occurring mainly in the paratesticular and head and neck
regions. Cytological reports of spindle-cell RMS have been sparse in the
literature and the awareness of its cytological features is not very wide among
cytopathologists. A 2-year-old girl was brought to clinical attention for a
progressively enlarging swelling of right thumb. Imaging studies showed it to be
a soft-tissue tumor in the subcutaneous region. Fine-needle aspiration yielded
moderately cellular smears composed of small, round cells and few spindle cells
with tapered cytoplasm. A cytological impression of RMS was rendered, which was
later confirmed as spindle-cell RMS on excision biopsy. Spindle-cell RMS, a
favorable prognostic variant of embryonal RMS, should be considered in the
cytologic diagnosis of soft-tissue tumors with round cell and spindle cell
morphology. This is especially true for tumors occurring in hitherto unreported
sites. Diagn. Cytopathol. 2016;44:1094-1097. (c) 2016 Wiley Periodicals, Inc.
PMID- 27502216
TI - Disorganized Amygdala Networks in Conduct-Disordered Juvenile Offenders With
Callous-Unemotional Traits.
AB - BACKGROUND: The developmental trajectory of psychopathy seemingly begins early in
life and includes the presence of callous-unemotional (CU) traits (e.g.,
deficient emotional reactivity, callousness) in conduct-disordered (CD) youth.
Though subregion-specific anomalies in amygdala function have been suggested in
CU pathophysiology among antisocial populations, system-level studies of CU
traits have typically examined the amygdala as a unitary structure. Hence,
nothing is yet known of how amygdala subregional network function may contribute
to callous-unemotionality in severely antisocial people. METHODS: We addressed
this important issue by uniquely examining the intrinsic functional connectivity
of basolateral amygdala (BLA) and centromedial amygdala (CMA) networks across
three matched groups of juveniles: CD offenders with CU traits (CD/CU+; n = 25),
CD offenders without CU traits (CD/CU-; n = 25), and healthy control subjects (n
= 24). We additionally examined whether perturbed amygdala subregional
connectivity coincides with altered volume and shape of the amygdaloid complex.
RESULTS: Relative to CD/CU- and healthy control youths, CD/CU+ youths showed
abnormally increased BLA connectivity with a cluster that included both dorsal
and ventral portions of the anterior cingulate and medial prefrontal cortices,
along with posterior cingulate, sensory associative, and striatal regions. In
contrast, compared with CD/CU- and healthy control youths, CD/CU+ youths showed
diminished CMA connectivity with ventromedial/orbitofrontal regions. Critically,
these connectivity changes coincided with local hypotrophy of BLA and CMA
subregions (without being statistically correlated) and were associated to more
severe CU symptoms. CONCLUSIONS: These findings provide unique insights into a
putative mechanism for perturbed attention-emotion interactions, which could bias
salience processing and associative learning in youth with CD/CU+.
PMID- 27502217
TI - Representing genetic variation with synthetic DNA standards.
AB - The identification of genetic variation with next-generation sequencing is
confounded by the complexity of the human genome sequence and by biases that
arise during library preparation, sequencing and analysis. We have developed a
set of synthetic DNA standards, termed 'sequins', that emulate human genetic
features and constitute qualitative and quantitative spike-in controls for genome
sequencing. Sequencing reads derived from sequins align exclusively to an
artificial in silico reference chromosome, rather than the human reference
genome, which allows them them to be partitioned for parallel analysis. Here we
use this approach to represent common and clinically relevant genetic variation,
ranging from single nucleotide variants to large structural rearrangements and
copy-number variation. We validate the design and performance of sequin standards
by comparison to examples in the NA12878 reference genome, and we demonstrate
their utility during the detection and quantification of variants. We provide
sequins as a standardized, quantitative resource against which human genetic
variation can be measured and diagnostic performance assessed.
PMID- 27502218
TI - Spliced synthetic genes as internal controls in RNA sequencing experiments.
AB - RNA sequencing (RNA-seq) can be used to assemble spliced isoforms, quantify
expressed genes and provide a global profile of the transcriptome. However, the
size and diversity of the transcriptome, the wide dynamic range in gene
expression and inherent technical biases confound RNA-seq analysis. We have
developed a set of spike-in RNA standards, termed 'sequins' (sequencing spike
ins), that represent full-length spliced mRNA isoforms. Sequins have an entirely
artificial sequence with no homology to natural reference genomes, but they align
to gene loci encoded on an artificial in silico chromosome. The combination of
multiple sequins across a range of concentrations emulates alternative splicing
and differential gene expression, and it provides scaling factors for
normalization between samples. We demonstrate the use of sequins in RNA-seq
experiments to measure sample-specific biases and determine the limits of
reliable transcript assembly and quantification in accompanying human RNA
samples. In addition, we have designed a complementary set of sequins that
represent fusion genes arising from rearrangements of the in silico chromosome to
aid in cancer diagnosis. RNA sequins provide a qualitative and quantitative
reference with which to navigate the complexity of the human transcriptome.
PMID- 27502219
TI - Africa's jungle and the arch: Of elephants and CHIMPS.
PMID- 27502220
TI - "Foot and Ankle Surgery" is awarded its first impact factor.
PMID- 27502221
TI - Does external fixation result in superior ankle function than open reduction
internal fixation in the management of adult distal tibial plafond fractures?
AB - BACKGROUND: Traditionally distal tibial plafond fractures were managed with open
reduction internal fixation however, high complication rates have prompted the
use of external fixation as an alternative. No definitive review has been
conducted and the issue of superior treatment method remains contentious. This
review assesses the comparative effectiveness of both with regards ankle
function. METHOD: A search strategy was formulated with keywords ensuring full
use of Medical Subject Headings terms for maximum sensitivity with Boolean
combinations. Multiple databases were used. RESULTS: All papers had limitations,
hence results and conclusions must be considered conservatively. Paper-1
demonstrated an association between ORIF and superior ankle function (P<0.05).
Papers-2 and -3 demonstrated no significant difference (P>0.05) between treatment
techniques. CONCLUSIONS: Neither method can yet be widely advocated as superior
with the treatment method chosen remaining primarily on surgeon preference and
experience. This review highlights the requirement for further, high-quality
research in this area.
PMID- 27502222
TI - Short term results of the Mobility Total Ankle System: Clinical and radiographic
outcome.
AB - BACKGROUND: Ankle arthroplasty is increasingly used to reduce pain and improve or
maintain joint mobility in end-stage ankle arthritis. The aim of this study was
to assess the clinical and radiographic short term results of the Mobility
prosthesis. METHODS: Complications, secondary operations, failures and the
survival rate were retrospectively examined in 67 primary Mobility total ankle
arthroplasties. Prosthesis alignment was measured and patient reported outcomes
were assessed with the use of questionnaires. RESULTS: There were two
intraoperative and 13 postoperative complications, requiring seven reoperations.
Failure occurred in three cases, with a survival of 95% after 61 months. Clinical
scores improved after surgery and alignment was correct in 93% of the tibial and
93% of the talar components. CONCLUSION: Despite few intraoperative complications
and satisfactory clinical and radiological outcome, the incidence of
postoperative complications, reoperations and failure indicate the importance of
further development and research in the field of ankle arthroplasty.
PMID- 27502223
TI - Comparison of modern locked plating and antiglide plating for fixation of
osteoporotic distal fibular fractures.
AB - BACKGROUND: Fractures in osteoporotic patients can be difficult to treat because
of poor bone quality and inability to gain screw purchase. The purpose of this
study is to compare modern lateral periarticular distal fibula locked plating to
antiglide plating in the setting of an osteoporotic, unstable distal fibula
fracture. METHODS: AO/OTA 44-B2 distal fibula fractures were created in sixteen
paired fresh frozen cadaveric ankles and fixed with a lateral locking plate and
an independent lag screw or an antiglide plate with a lag screw through the
plate. The specimens underwent stiffness, cyclic loading, and load to failure
testing. The energy absorbed until failure, torque to failure, construct
stiffness, angle at failure, and energy at failure was recorded. RESULTS: The
lateral locking construct had a higher torque to failure (p=0.02) and construct
stiffness (p=0.04). The locking construct showed a trend toward increased angle
at failure, but did not reach statistical significance (p=0.07). Seven of the
eight lateral locking plate specimens failed through the distal locking screws,
while the antiglide plating construct failed with pullout of the distal screws
and displacement of the fracture in six of the eight specimens. CONCLUSION: In
our study, the newly designed distal fibula periarticular locking plate with
increased distal fixation is biomechanically stronger than a non-locking one
third tubular plate applied in antiglide fashion for the treatment of AO/OTA 44
B2 osteoporotic distal fibula fractures. LEVEL OF EVIDENCE: V: This is an ex-vivo
study performed on cadavers and is not a study performed on live patients.
Therefore, this is considered Level V evidence.
PMID- 27502224
TI - Is arthroscopic assisted percutaneous screw fixation as good as open reduction
and internal fixation for the treatment of displaced intra-articular calcaneal
fractures?
AB - BACKGROUND: This study compares the outcomes of calcaneal fracture surgery after
open reduction internal fixation and plating (ORIF) versus arthroscopic assisted
percutaneous screw fixation (APSF). METHODS: Group I (N=12) underwent ORIF. Group
II (N=15) underwent APSF. Anthropometric data, pre and post-operative stay,
complications and duration off work were recorded in this retrospective case
cohort study. Radiographs were analyzed for Bohler's, Gissane's angle and
Sanders' classification. AOFAS Hindfoot and SF 36 scores were collected at final
follow-up. RESULTS: Anthropometric data, Bohler's and Gissane's angles, AOFAS and
SF 36 scores were not significantly different. Pre-operative duration was 12.3
days in ORIF and 6.9 days in APSF. Post-operative duration was 7.3 days vs 3.8
days. Duration off work was 6.2 months vs 2.9 months. CONCLUSION: The APSF group
was able to have surgery earlier, go home faster, and return to work earlier.
This study was not powered to demonstrate a difference in wound complication
rates.
PMID- 27502225
TI - Randomised comparison of two skin preparation methods in foot and ankle surgery.
AB - BACKGROUND: Foot and ankle surgery has an increased incidence of post-operative
surgical site infections. The aim of this study was to examine the efficacy and
efficiency of an alternative method of surgical site preparation for foot and
ankle surgery. METHOD: Fifty-one volunteers were recruited for this study which
compared standard gauze painting using 2% chlorhexidine with 70% alcohol to
immersion of the foot and ankle in a non-sterile bag filled with 60mL of the same
solution and rubbing all skin surfaces (bag immersion method). Each method was
applied to different feet of each volunteer in a randomised order. Commercially
available impression agar slides were used to measure bacteria colony-forming
unit (CFU) counts from four areas of each foot after allowing the preparation to
dry. Outcomes included CFU count and preparation time. RESULT: There was no
difference between the methods in terms of CFU count (0 total CFU vs. 1).
Preparation time was significantly shorter for the bag immersion method (63.98s
vs. 67.98s). Two-side 90% confidence intervals (2.03-6.00) for the difference in
means of preparation time demonstrated equivalence using a margin of +/-20%.
CONCLUSIONS: The bag immersion method is a valid alternative, equivalent in
preparation timing and the elimination of transient skin flora when using 2%
Chlorhexidine with 70% alcohol.
PMID- 27502226
TI - 5 year retrospective follow-up of new cases of Charcot neuroarthropathy-A single
centre experience.
AB - BACKGROUND: Few data describe the natural history of Charcot neuroarthropathy
treated with a total contact plaster cast (TCC). METHODS: A 5 year retrospective
analysis of 50 patients presenting with an acute CN, Assessing time to clinical
resolution into appropriate footwear and assessing if initial immobilisation
device influenced resolution time. RESULTS: During the study period 42 patients
(84%) of patients went into remission, 2 died during their treatment, 4 had major
amputations, in 2 patients treatment was ongoing. 36 patients were treated with
combination offloading devices, 6 were treated with one modality only. Median
time to resolution for patients initially treated with a TCC was not
significantly shorter than for those treated with a removable below knee boot.
34.9% required re-casting due to clinical deterioration in the removable device.
CONCLUSIONS: More precise measures of resolution of CN are needed to assess the
impact of initial treatment modality on time to resolution.
PMID- 27502227
TI - Modified Chevron osteotomy for hallux valgus deformity in female athletes. A 2
year follow-up study.
AB - BACKGROUND: Hallux valgus is an increasingly common deformity in young female
athletes that constricts their daily athletic activities and influences foot
cosmesis. The aim of this study was to evaluate the outcome of modified Chevron
osteotomy for hallux valgus deformity in this specific population. METHODS: Forty
two cases of modified Chevron osteotomies were carried out in 33 patients with
mild to moderate hallux valgus deformity. Each participant was evaluated for
AOFAS score, pain, range of motion, cosmetic and radiological outcome. RESULTS:
Mean AOFAS score improved to 96.3 (p<0.001) while the mean range of motion of the
metatarsophalangeal joint was maintained (p=0.138). The cosmetic result was
excellent/good in 40 cases (95%). Mean metatarsophalangeal and intermetatarsal
angles were decreased from 29.8 degrees and 14.2 degrees preoperatively to 12.2
degrees and 8.1 degrees postoperatively (p<0.001 and p<0.036), respectively.
CONCLUSIONS: Modified Chevron osteotomy could offer substantial correction of
hallux valgus deformity in young female athletes, with excellent clinical
outcome.
PMID- 27502228
TI - Posterior ankle and hindfoot endoscopy: A cadaveric study.
AB - BACKGROUND: The list of indications of posterior ankle endoscopy is expanding and
includes various soft tissue and bony pathologies of the posterior ankle. Some of
the indications, e.g. release of frozen ankle, debridement of posteromedial soft
tissue impingement of the ankle and debridement or fixation of the posteromedial
osteochondral lesion of the talus, require approach to the posterior ankle medial
to the flexor hallucis longus tendon. The purpose of this study was to assess the
risk of injury to the posterior tibial neurovascular bundle during posterior
ankle endoscopy. METHODS: Fourteen fresh frozen foot and ankle specimens were
used. A metal rod was inserted into the posteromedial, posterolateral and
modified posteromedial portals and touched the medial border of the
posterolateral talar tubercle and the posteromedial corner of the ankle mortise
in turn. The neurovascular bundle and FHL tendon were examined for any kink.
RESULTS: The neurovascular bundle was kinked in all specimens (100%) with the rod
at the posteromedial corner of the ankle mortise through the posteromedial portal
and was kinked in 11 specimens (79%) with the rod through the modified
posteromedial portal. The neurovascular bundle was kinked in 1 specimen (7%) with
the rod through the posterolateral portal. CONCLUSIONS: The neurovascular bundle
was at risk during instrumentation of the posteromedial ankle through the
posteromedial portal but was safe through the posterolateral portal.
PMID- 27502229
TI - A critical evaluation of venous thromboembolism risk assessment models used in
patients with lower limb cast immobilisation.
AB - BACKGROUND: There is a recognised link between lower limb cast immobilisation and
the development of venous thromboembolism (VTE). Our aim was to assess the
diagnostic accuracy of risk assessment models (RAMs) applicable to this patient
group. This has not been done before. METHODS: A literature and guideline review
identified five RAMs. They were used to retrospectively risk assess a consecutive
series of patients who were diagnosed with symptomatic VTE following lower limb
injury treated with a cast (Group I). A case-matched cohort who did not suffer
symptomatic VTE (Group II) was also retrospectively risk assessed. The RAMs'
diagnostic performance indicators were calculated. RESULTS: Groups I and II
consisted of 21 patients each. There was no significant difference in the mean
age or total number of VTE risk factors between Groups I and II (p=.957 and
p=.878 respectively). The Plymouth (2010) RAM achieved the highest accuracy
(54.8%). CONCLUSIONS: Each RAM demonstrated significant limitations. Two
displayed very limited clinical utility. Three recommended chemical
thromboprophylaxis to all patients because they weighted lower limb
immobilisation as an absolute risk factor for the development of VTE. Cast
immobilisation should not be considered an absolute risk factor when risk
assessing patients who all have casts. Prospective evaluation with a larger
patient cohort is required.
PMID- 27502230
TI - Interosseous membrane window size for tibialis posterior tendon transfer
Geometrical and MRI analysis.
AB - BACKGROUND: Tibialis posterior (TP) tendon transfer through the interosseous
membrane is commonly performed in Charcot-Marie-Tooth disease. In order to avoid
entrapment of this tendon, no clear recommendation relative to the interosseous
membrane (IOM) incision size has been made. OBJECTIVE: Analyze the TP size at the
transfer level and therefore determine the most adequate IOM window size to avoid
muscle entrapment. METHODS: Eleven lower extremity magnetic resonances were
analyzed. TP muscle measurements were made in axial views, obtaining the medial
lateral and antero-posterior diameter at various distances from the medial
malleolus tip. The distance from the posterior to anterior compartment was also
measured. These measurements were applied to a mathematical model to predict the
IOM window size necessary to allow an ample TP passage in an oblique direction.
RESULTS: The average tendon diameter (confidence-interval) at 15cm proximal to
the medial malleolus tip was 19.47mm (17.47-21.48). The deep posterior
compartment to anterior compartment distance was 10.97mm (9.03-12.90). Using a
mathematical model, the estimated IOM window size ranges from 4.2 to 4.9cm.
CONCLUSION: The IOM window size is of utmost importance in trans-membrane TP
transfers, given that if equal or smaller than the transposed tendon oblique
diameter, a high entrapment risk exists. A membrane window of 5cm or 2.5 times
the size of the tendon diameter should be performed in order to theoretically
diminish this complication.
PMID- 27502231
TI - Talolisthesis in end stage ankle arthrosis.
AB - BACKGROUND: Sagittal displacement in patients with end stage ankle arthritis has
been described as the tibiotalar ratio (TTR). Yet the incidence, distribution and
predictive factors of talolisthesis are unknown. METHODS: The radiographs of 470
cases of ankle arthritis were compared with a control group of 49 normal ankles.
The TTR was measured for both groups. Additional co-variables included the
anterior and lateral distal tibial angles, and talar tilt. RESULTS: The mean TTR
in the arthritis cohort was 34.8+9.12 compared to the normal group of 34.1+2.62.
Twenty-eight percent of the ankles had anterior displacement and twenty-eight
percent had posterior talolisthesis, while forty-four percent had normal
tibiotalar alignment. Multivariate linear regression revealed significant
predictors of anterior distal tibial angle (p<0.0001) and talar tilt (p=0.0007)
for abnormal TTR. CONCLUSION: Sagittal displacement is common in end stage ankle
arthritis and is affected by ligamentous laxity and joint morphology.
PMID- 27502232
TI - Talonavicular joint arthroscopic portals: A cadaveric study of feasibility and
safety.
AB - BACKGROUND: The objectives of the study were to evaluate the safety of
hypothetical arthroscopic portals from talonavicular joint and to evaluate their
reproducibility and enforceability. METHODS: 19 cadaveric feet were marked and
four arthroscopic portals were made (medial, dorsomedial, dorsolateral and
lateral). The specimens were dissected in layers and the distances between
neurovascular structures and the trocars were measured. RESULTS: Medial and
dorsomedial portals were in average 8.3 and 8.7, respectively, to the saphenous
vein and nerve. Dorsolateral portal was in average 8.1mm to the deep peroneal
nerve and dorsalis pedis artery, and 9.1mm to the medial dorsal cutaneous branch
of the superficial peroneal nerve. Lateral portal was in average 12.3mm to the
intermediate dorsal cutaneous branch of the superficial peroneal nerve.
CONCLUSION: Tested portals shown to have a good safety margin for the foot
neurovascular deep dorsal structures and an acceptable safety margin for the
superficial neurovascular structures.
PMID- 27502233
TI - Syndesmosis preserving osteotomy of the fibula for access to the lateral talar
dome.
AB - BACKGROUND: Open surgical access to the postero-lateral talar dome for the
treatment of osteochondral lesions is challenging, often requiring a segmental
osteotomy of the fibula (fibular window) and division of the anterior inferior
tibiofibular ligament (AITFL) or a fibular osteotomy with division of the AITFL
and the anterior talofibular ligament (ATFL) (fibular door). Alternatively, to
preserve the tibiofibular syndesmosis both the fibula and the lateral tibial
plafond can be osteotomised to expose the entire lateral talar dome. All of these
techniques involve extensive surgical exposures and a significant amount of
internal fixation of the osteotomy to achieve surgical access. METHODS: A
trapezoidal fibular osteotomy which hinges on the AITFL thus preserving the
syndesmotic and lateral ligamentous complex was developed to permit perpendicular
access to the lateral talar dome. The remaining posterior column of fibula allows
keying in of the osteotomy requiring minimal internal fixation. RESULTS: A 43
year old male with a displaced osteochondral fracture of the superolateral talar
dome underwent the osteotomy to provide perpendicular fixation with two Herbert's
screws. The osteotomy was reduced and fixed with a single 3.5mm lag screw. At 3
month follow up the osteotomy had healed both clinically and radiographically.
CONCLUSIONS: Our technique utilizes a novel trapezoidal fibular osteotomy with
preservation of key syndesmotic and ligamentous structures and requires minimal
internal fixation.
PMID- 27502234
TI - Letter to the editor on "A standard shoelace prevents equinus posturing of the
ankle during circular external fixation of the tibia".
PMID- 27502235
TI - Response to: "Re: Standard shoelace prevents equinus posturing of the ankle
during circular external fixation of the tibia". Manuscript 14-00002.
PMID- 27502236
TI - Conversion of ankle autofusion to total ankle replacement using the Salto XT
revision prosthesis.
AB - Few reports in the literature have described the conversion of a surgically fused
ankle to a total ankle replacement. The takedown of an autofusion and conversion
to a prosthesis has not been described. We report the case of a patient with
severe rheumatoid arthritis with an ankle autofusion fixed in equinus and severe
talonavicular arthritis that was converted to ankle replacement using the Salto
XT revision system. We describe the reasons why the decision was made to perform
total ankle arthroplasty while concomitantly fusing the talonavicular joint, and
discuss the rationale of the various surgical treatment options considered. We
describe the clinical and radiographic outcomes achieved in this case. At 12
months post-operatively the patient reported significant reduction of pain,
increased FAOS scores and had increased ankle range of motion.
PMID- 27502237
TI - Poncet's disease (tubercular rheumatism) with primary involvement of the foot - A
case report.
AB - We present a rare case with primary tubercular involvement of the foot,
accomapanied by a reactionary (aseptic) effusion in the knee. The diagnosis was
delayed due to unusual presentation and also because of failure to elicit a
detailed history. Incision and drainage of the foot abscess and antitubercular
drug therapy resulted in satisfactory control of tubercular infection.
Polyarticular presentation may not always signify active tubercular focus in
every joint; it may reflect reactive synovitis known as Poncet's disease, which
resolves with multidrug antitubercular therapy.A multidispilinary approach should
be adopted and chest physicians, rheumatologists and orthopaedic surgeons should
work in close association to correctly diagnose and treatthis condition.
PMID- 27502238
TI - Hereditary Heterozygous C2 Deficiency: Variable Clinical and Serological
Manifestations Among Three Sisters.
AB - The causal link between inherited complement deficiencies and systemic lupus
erythematosus (SLE) has been well established, although it remains a rare cause
of the disease. We present the case of three biological sisters with hereditary
heterozygous C2 deficiency, but who differ widely in their clinical and
serological manifestations. Patient 1 is 25 years old and was diagnosed with SLE
at the age of 12. Further testing revealed positive ANA and anti-dsDNA,
antiphospholipid syndrome (APS) and decreased C2, C3 and C4 levels. Patients 2
and 3 are 21-year-old dizygotic twins. Both have positive ANA and
antiphospholipid (APL) antibodies, and decreased C2 and C4 levels. We present a
case of familial heterozygous C2 deficiency with different disease phenotypes.
The presence of positive APL antibodies in all 3 patients is significant, as this
association has been rarely described. The variable clinical and serological
manifestations among our patients further reflect the complex and multifactorial
nature of SLE.
PMID- 27502240
TI - Quantity Distortion Effect in Consumers' Perception of Different Volumes and
Weights of Money: A Pilot Study.
AB - Consumers tend to misunderstand the physical value of cash money by adopting
improper anchors for their judgments (e.g., banknote size and shape, currency
denominations, etc.). In a pilot study carried out on a sample of 242
participants (n = 116 men; M age = 29.6 year, SD = 10.8), a quantity distortion
effect was demonstrated by evaluating consumers' misperceptions of different
monetary quantities, either in terms of volume or weight, using banknotes of the
same denomination (?50). A threshold value was found, for both volume (?876,324)
and weight (?371,779), above (below) which consumers tend to overrate (underrate)
monetary amounts. The theoretical and operative implications are discussed.
PMID- 27502239
TI - Non-invasive real-time biopsy of intracranial lesions using short time expanded
circulating tumor cells on glass slide: report of two cases.
AB - BACKGROUND: Circulating Tumor Cells (CTCs) are promising biomarkers for
monitoring solid cancer and were used to monitor brain tumors. Here we report two
cases in which, for the first time, CTCs were used in cytological diagnostic
evaluation to discriminate a space-occupying lesion of the brain. CASE
PRESENTATION: Two cases of focal intracranial lesions, unclassified for
diagnosis, untreated and apparently symptomatic, were examined after high
contrast resolution Magnetic Resonance Imaging and/or Computed Tomography scans.
CTCs were seeded on chamber slides and short-time expanded under the optimized
conditions as we previously reported. The first case was a focal lesion localized
in the parietal-occipital area in a 67-year-old woman. The second case was a 31
year-old man with an expansive intracerebral lesion localized in the left peri
trigonal area. Both patients underwent excisional biopsy. Histopathological
evaluation of the biopsy confirmed the previous cytological diagnoses, and the
analysis of the clinical outcomes retrospectively validated both diagnoses.
CONCLUSIONS: The cases here reported illustrate the potential for using expanded
CTCs as non-invasive, real-time biopsy. Moreover, non-invasive real-time biopsy
can represent an alternative diagnostic tool to be used when a functional area of
the brain is at risk of injury from excisional biopsy procedures.
PMID- 27502241
TI - Force Irregularity Following Maximal Effort: The After-Peak Reduction.
AB - Irregularities in force output are present throughout human movement and can
impair task performance. We investigated the presence of a large force
discontinuity (after-peak reduction, APR) that appeared immediately following
peak in maximal effort ramp contractions performed with the thumb adductor and
ankle dorsiflexor muscles in 25 young adult participants (76% males, 24% females;
M age 24.4 years, SD = 7.1). The after-peak reduction displayed similar
parameters in both muscle groups with comparable drops in force during the after
peak reduction minima (thumb adductor: 27.5 +/- 7.5% maximal voluntary
contraction; ankle dorsiflexor: 25.8 +/- 6.2% maximal voluntary contraction). A
trend for the presence of fewer after-peak reductions with successive ramp trials
was observed, suggesting a learning effect. Further investigation should explore
underlying neural mechanisms contributing to the after-peak reduction.
PMID- 27502242
TI - Attentional Focus in Motor Learning, the Feldenkrais Method, and Mindful
Movement.
AB - The present paper discusses attentional focus in motor learning and performance
from the point of view of mindful movement practices, taking as a starting point
the Feldenkrais method. It is argued that earlier criticism of the Feldenkrais
method (and thereby implicitly of mindful movement practices more generally)
because of allegedly inappropriate attentional focus turns out to be unfounded in
light of recent developments in the study of motor learning and performance.
Conversely, the examples of the Feldenkrais method and Ki-Aikido are used to
illustrate how both Western and Eastern (martial arts derived) mindful movement
practices might benefit sports psychology.
PMID- 27502243
TI - Postural Control During Cascade Ball Juggling: Effects of Expertise and Base of
Support.
AB - Cascade ball juggling is a complex perceptual motor skill which requires
efficient postural stabilization. The aim of this study was to investigate
effects of experience (expert and intermediate groups) and foot distance (wide
and narrow stances) on body sway of jugglers during three ball cascade juggling.
A total of 10 expert jugglers and 11 intermediate jugglers participated in this
study. Participants stood barefoot on the force plate (some participants wore a
gaze tracking system), with feet maintained in wide and narrow conditions and
performed three 40-seconds trials of the three-ball juggling task. Dependent
variables were sway mean velocity, amplitude, mean frequency, number of ball
cycles, fixation number, mean duration and its variability, and area of gaze
displacement. Two-way analyses of variance with factors for group and condition
were conducted. Experts' body sway was characterized by lower velocity and
smaller amplitude as compared to intermediate group. Interestingly, the more
challenging (narrow) basis of support caused significant attenuation in body sway
only for the intermediate group. These data suggest that expertise in cascade
juggling was associated with refined postural control.
PMID- 27502244
TI - Competitive Performance Correlates of Mental Toughness in Tennis: A Preliminary
Analysis.
AB - This study investigated relationships between mental toughness and measures of
competitive performance in tennis. Forty-three male (N = 25) and female (N = 18)
players (M age = 13.6 years, SD = 2.4) completed the mental toughness inventory,
and the point-by-point outcomes recorded during a competitive tennis match
(singles) were used to generate performance indices for each athlete. The results
indicated that mental toughness was associated with several, but not all, macro,
micro, and critical moment performance indices. The findings suggest mental
toughness may contribute to successful performance during tennis competition,
although the importance of the construct appears to depend depend on specific
match situations. Future mental toughness research should consider a range of
factors related to sport performance, including athletes' and opponents'
physical, technical, and tactical abilities.
PMID- 27502245
TI - Cartilage inflammation and degeneration is enhanced by pro-inflammatory (M1)
macrophages in vitro, but not inhibited directly by anti-inflammatory (M2)
macrophages.
AB - OBJECTIVE: Macrophages play a crucial role in the progression of osteoarthritis
(OA). Their phenotype may range from pro-inflammatory to anti-inflammatory. The
aim of this study was to evaluate the direct effects of macrophage subtypes on
cartilage by culturing macrophage conditioned medium (MCM) on human articular
cartilage. DESIGN: Human OA cartilage explants were cultured with MCM of pro
inflammatory M(IFNgamma+TNFalpha), or anti-inflammatory M(IL-4) or M(IL-10) human
monocyte-derived macrophages. To assess effects of anti-inflammatory macrophages,
the cartilage was cultured with a combination of MCM phenotypes as well as pre
stimulated with IFNgamma+TNFalpha cartilage before culture with MCM. The
reactions of the explants were assessed by gene expression, nitric oxide (NO)
production and release of glycosaminoglycans (GAGs). RESULTS:
M(IFNgamma+TNFalpha) MCM affected OA cartilage by upregulation of IL1B
(Interleukin 1beta), IL6, MMP13 (Matrix Metalloproteinase-13) and ADAMTS5 (A
Disintegrin And Metalloproteinase with Thrombospondin Motifs-5), while inhibiting
ACAN (aggrecan) and COL2A1 (collagen type II). M(IL-10) upregulated IL1B and
Suppressor of cytokine signaling 1 (SOCS1). NO production and GAG release by the
cartilage was increased when cultured with M(IFNgamma+TNFalpha) MCM. M(IL-4) and
M(IL-10) did not inhibit the effects of M(IFNgamma+TNFalpha) MCM of neither
phenotype affected IFNgamma+TNFalpha pre-stimulated cartilage, in which an
inflammatory gene response was deliberately induced. CONCLUSION:
M(IFNgamma+TNFalpha) macrophages have a prominent direct effect on OA cartilage,
while M(IL-4) and M(IL-10) do not inhibit the effects of M(IFNgamma+TNFalpha), or
IFNgamma+TNFalpha induced inflammation of the cartilage. Therapies aiming at
inhibiting cartilage degeneration may take this into account by directing
suppression of pro-inflammatory macrophages or stimulation of anti-inflammatory
macrophages.
PMID- 27502246
TI - Rift Valley fever vector diversity and impact of meteorological and environmental
factors on Culex pipiens dynamics in the Okavango Delta, Botswana.
AB - BACKGROUND: In Northern Botswana, rural communities, livestock, wildlife and
large numbers of mosquitoes cohabitate around permanent waters of the Okavango
Delta. As in other regions of sub-Saharan Africa, Rift Valley Fever (RVF) virus
is known to circulate in that area among wild and domestic animals. However, the
diversity and composition of potential RVF mosquito vectors in that area are
unknown as well as the climatic and ecological drivers susceptible to affect
their population dynamics. METHODS: Using net traps baited with carbon dioxide,
monthly mosquito catches were implemented over four sites surrounding cattle
corrals at the northwestern border of the Okavango Delta between 2011 and 2012.
The collected mosquito species were identified and analysed for the presence of
RVF virus by molecular methods. In addition, a mechanistic model was developed to
assess the qualitative influence of meteorological and environmental factors such
as temperature, rainfall and flooding levels, on the population dynamics of the
most abundant species detected (Culex pipiens). RESULTS: More than 25,000
mosquitoes from 32 different species were captured with an overabundance of Cx.
pipiens (69,39 %), followed by Mansonia uniformis (20,67 %) and a very low
detection of Aedes spp. (0.51 %). No RVF virus was detected in our mosquito
pooled samples. The model fitted well the Cx. pipiens catching results (rho =
0.94, P = 0.017). The spatial distribution of its abundance was well represented
when using local rainfall and flooding measures (rho = 1, P = 0.083). The global
population dynamics were mainly influenced by temperature, but both rainfall and
flooding presented a significant influence. The best and worst suitable periods
for mosquito abundance were around March to May and June to October,
respectively. CONCLUSIONS: Our study provides the first available data on the
presence of potential RVF vectors that could contribute to the maintenance and
dissemination of RVF virus in the Okavango Delta. Our model allowed us to
understand the dynamics of Cx. pipiens, the most abundant vector identified in
this area. Potential predictions of peaks in abundance of this vector could allow
the identification of the most suitable periods for disease occurrence and
provide recommendations for vectorial and disease surveillance and control
strategies.
PMID- 27502247
TI - MR perfusion-weighted imaging in the evaluation of high-grade gliomas after
treatment: a systematic review and meta-analysis.
AB - BACKGROUND: Distinction between tumor and treatment related changes is crucial
for clinical management of patients with high-grade gliomas. Our purpose was to
evaluate whether dynamic susceptibility contrast-enhanced (DSC) and dynamic
contrast enhanced (DCE) perfusion-weighted imaging (PWI) metrics can effectively
differentiate between recurrent tumor and posttreatment changes within the
enhancing signal abnormality on conventional MRI. METHODS: A comprehensive
literature search was performed for studies evaluating PWI-based differentiation
of recurrent tumor and posttreatment changes in patients with high-grade gliomas
(World Health Organization grades III and IV). Only studies published in the
"temozolomide era" beginning in 2005 were included. Summary estimates of
diagnostic accuracy were obtained by using a random-effects model. RESULTS: Of
1581 abstracts screened, 28 articles were included. The pooled sensitivities and
specificities of each study's best performing parameter were 90% and 88% (95% CI:
0.85-0.94; 0.83-0.92) and 89% and 85% (95% CI: 0.78-0.96; 0.77-0.91) for DSC and
DCE, respectively. The pooled sensitivities and specificities for detecting tumor
recurrence using the 2 most commonly evaluated parameters, mean relative cerebral
blood volume (rCBV) (threshold range, 0.9-2.15) and maximum rCBV (threshold
range, 1.49-3.1), were 88% and 88% (95% CI: 0.81-0.94; 0.78-0.95) and 93% and 76%
(95% CI: 0.86-0.98; 0.66-0.85), respectively. CONCLUSIONS: PWI-derived thresholds
separating viable tumor from treatment changes demonstrate relatively good
accuracy in individual studies. However, because of significant variability in
optimal reported thresholds and other limitations in the existing body of
literature, further investigation and standardization is needed before
implementing any particular quantitative PWI strategy across institutions.
PMID- 27502248
TI - Radiogenomics to characterize regional genetic heterogeneity in glioblastoma.
AB - BACKGROUND: Glioblastoma (GBM) exhibits profound intratumoral genetic
heterogeneity. Each tumor comprises multiple genetically distinct clonal
populations with different therapeutic sensitivities. This has implications for
targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI
and conventional sampling techniques have failed to resolve this heterogeneity,
particularly for nonenhancing tumor populations. This study explores the
feasibility of using multiparametric MRI and texture analysis to characterize
regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor
segments. METHODS: We collected multiple image-guided biopsies from primary GBM
patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so
called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number
variants for core GBM driver genes reported by The Cancer Genome Atlas. We co
registered biopsy locations with MRI and texture maps to correlate regional
genetic status with spatially matched imaging measurements. We also built
multivariate predictive decision-tree models for each GBM driver gene and
validated accuracies using leave-one-out-cross-validation (LOOCV). RESULTS: We
collected 48 biopsies (13 tumors) and identified significant imaging correlations
(univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and
TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest.
Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%),
and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4
driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples
(n = 16) compared with those from ENH segments (n = 32). CONCLUSION: MRI and
texture analysis can help characterize regional genetic heterogeneity, which
offers potential diagnostic value under the paradigm of individualized oncology.
PMID- 27502249
TI - Ruxolitinib in steroid refractory graft-vs.-host disease: a case report.
AB - BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) is
potentially curative in a variety of hematological malignancies. Graft-vs.-host
disease (GvHD) remains a life-threatening complication. Standard treatment is
high-dose (HD) corticosteroids. Steroid-refractory (SR) GvHD is associated with
poor prognosis. At present, second-line treatment is ill-defined and includes a
number of agents. Novel insights into the pathophysiology of acute GvHD (aGvHD)
highlight the relevant role of the host inflammatory response governed by several
kinase families, including Janus kinases (JAK)1/2. Ruxolitinib, a JAK1/2
inhibitor approved for intermediate-2/high-risk myelofibrosis, was recently
employed in SR-GvHD with encouraging overall response rates. Clinical experience
however remains limited. CASE PRESENTATION: A 51-year-old male with refractory
anemia with excess blast type-2 underwent a myeloablative allogeneic HSCT from a
9/10 HLA-matched unrelated donor after conditioning with busulfan and
cyclophosphamide. GvHD prophylaxis consisted of cyclosporine, methotrexate, and
thymoglobulin. CD34(+) cells/kg infused were 8.69 * 10(6) kg. On day 29, the
patient developed overall grade IV aGvHD with biopsy proven stage IV
gastrointestinal (GI) GvHD refractory to HD corticosteroids. Patient conditions
rapidly deteriorated and became critical despite the addition of mycophenolate
mofetil and budesonide. On day 33, Ruxolitinib was started, and on day 39 the
patient clinical conditions gradually improved. Complete resolution of aGvHD was
also confirmed by histology on day 54. CONCLUSIONS: At 5 months from HSCT, the
patient is well and in continuous hematological complete remission without flare
of GvHD. Ruxolitinib was discontinued on day 156. Ruxolitinib is feasible and
effective in SR-aGvHD though large prospective clinical trials are warranted.
PMID- 27502251
TI - Dermatologic Jottings I: George Orwell's Animal Farm Has Arrived.
PMID- 27502250
TI - Glycemic variability evaluated by continuous glucose monitoring system is
associated with the 10-y cardiovascular risk of diabetic patients with well
controlled HbA1c.
AB - BACKGROUND: The present study aimed to identify the relationship between glycemic
variability (GV) and the 10-y risk of cardiovascular disease (CVD) in type 2
diabetes mellitus (T2DM) patients with good glycemic control. METHODS: Two
hundred forty consecutive T2DM patients (HbA1c<=7.0%) without CVD were included
to calculate the 10-y CVD risk by Framingham risk score (FRS), and divided into 3
groups: low-risk group (FRS<=10%), intermediate-risk group (>10%, <=20%) and high
risk group (>20%). Inter-group differences of GV were determined by comparing the
SD of blood glucose (SDBG), mean amplitudes of glycemic excursion (MAGE), and
mean of daily differences (MODD) gathered from 72-h continuous glucose monitoring
system. RESULTS: The levels of SDBG and MAGE significantly increased along with
the raises of 10-y CVD risk of T2DM patients (p<0.01). FRS was positively
correlated with age, systolic blood pressure, SDBG and MAGE (r=0.717, 0.525,
0.509 and 0.485 respectively, p<0.01), while negatively correlated with the level
of HDL-C (r=-0.348, p<0.01). Furthermore, multivariate logistic regression
analysis confirmed that increased MAGE [OR: 1.623(1.198-2.316), p<0.001] and
patients with high urine albumin excretion rates [OR: 1.743(1.247-2.793),
p<0.001] were independent predictors for high 10-y CVD risk. CONCLUSION: GV
predicts independently the 10-y CVD risk of T2DM patients with well-controlled
HbA1c.
PMID- 27502252
TI - Erectile Dysfunction in Dermatology: It's Not As Hard As You Think.
PMID- 27502253
TI - Characteristics of Eccrine Tumors in a Tertiary Institution: A 5-Year
Retrospective Study.
AB - Eccrine tumors are adnexal tumors with a varied clinical presentation and wide
histological spectrum. This study aims to consolidate data on the clinical
characteristics of eccrine tumors to help improve clinical acumen and management
of such tumors. Histopathological records from January 2008 to December 2012 were
retrieved. Clinical characteristics of the tumor including site, appearance,
symptoms, color, duration prior to presentation, and clinical and histological
diagnosis were recorded. Eighty-four patients with eccrine tumors were
identified, with seven main types of tumors recognized-hidradenoma (33.3%),
poroma (29.8%), mixed tumors (14.3%), spiradenoma (8.3%), porocarcinoma (6.7%),
eccrine adenoma (3.6%), and syringoma (3.6%). A total of 50% of mixed tumors were
misdiagnosed as epidermal cysts. Eccrine tumors have a wide array of clinical
presentations and are often clinically misdiagnosed as cysts. Recognizing certain
clinical features may aid in the diagnosis, but, if in doubt, a biopsy should be
performed.
PMID- 27502254
TI - Clinical Efficacy and Safety of a Monopolar Radiofrequency Device With Comfort
Pulse Technology for the Treatment of Facial and Neck Laxity in Men.
AB - The objective of this study was to demonstrate the efficacy and safety of a
monopolar radiofrequency treatment for facial and neck laxity in men. Twelve men
received one treatment of the face and upper portion of the neck using an RF
system with comfort pulsed technology. Standardized photographs were taken at
baseline and at 1, 3, and 6 months of follow-up. Study investigators evaluated
facial and neck laxity at baseline and all follow-up visits using the Fasil
Laxity Scale. Patents and investigators assessed skin texture and overall
appearance using the Quartile Improvement Scale. Average improvement in treated
areas was statistically significant at 1-month (P<.01), 3-month (P=.02), and 6
month (P=.05) follow-up visits compared with baseline. Investigators rated
greatest improvement in skin texture and overall appearance (mild to moderate) at
the 3-month follow-up. Patient assessments demonstrated moderate improvement in
skin laxity, skin texture, and overall appearance maintained out to 6 months
after treatment. A total of 64% of patients were satisfied to very satisfied with
treatment at the 6-month follow-up. One RF treatment of the face and neck yielded
20% reduction in facial laxity 1 month after treatment, with maintained
improvement out to 6 months (15% reduction).
PMID- 27502255
TI - What Is Vitamin D3 and Its Potential Use in Dermatology?
AB - There are many clinical studies that show the importance of vitamin D in multiple
skin disorders. Understanding the molecular elements of cathelicidin expression
might lead to new treatments and help explain mechanisms of current therapies.
Overall, current data are generating many questions and expectations and require
larger trials to confirm the therapeutic use of vitamin D3 supplementation.
Vitamin D now represents a vast and promising field of research to
dermatologists.
PMID- 27502257
TI - Oral Mucosal Lesions: Miscellaneous-Part III.
AB - Oral mucosal lesions are a common occurrence in dermatology. In part III of this
series, the authors discuss the epidemiology and etiopathology of these lesions,
including clinical classifications, modifying factors, and incriminating agents.
PMID- 27502258
TI - A Leopard Can't Change Its Spots, but a Melanocyte Can! False-Negative MART-1
Staining.
PMID- 27502259
TI - JUBLIA (Efinaconazole): An Update.
PMID- 27502260
TI - Adult-Onset Still Disease Is on the Move.
PMID- 27502261
TI - Dermatology in a Bygone Era: Part II.
PMID- 27502262
TI - Lymphangioma Circumscriptum of the Vulva.
PMID- 27502263
TI - A Souvenir From France: Acrodermatitis Chronica Atrophicans Presenting in the
United States.
AB - A 70-year-old man was referred by his rheumatologist to our dermatology clinic
for evaluation of dermatitis on his right arm that appeared 3 months earlier. The
skin lesion was asymptomatic and the patient denied current systemic symptoms,
including fever, chills, and joint pain; however, 10 months prior to this
presentation he experienced arthritis in the left knee. At that time, Borrelia
serology revealed positive IgG (6.07; <0.8 negative, 0.8 to 0.99 borderline, >=1
positive) and negative IgM titers. The patient had not received treatment for
Lyme disease in the past. He was referred to rheumatology for evaluation of
possible Lyme disease but did not follow up until 10 months later. The arthritis
has since resolved. He travels frequently to France and recalls multiple tick
bites during these trips.
PMID- 27502264
TI - Porokeratotic Adnexal Ostial Nevus-Report of a Case With Unusual Clinical and
Histologic Features.
AB - An 11-year-old Tanzanian girl presented with diffuse verrucous lesions of varying
morphology, scarring alopecia, and keloid scars over the face with a predilection
for the ears. Physical examination revealed dark keratoderma and patches of
hypopigmentation near the midline of the dorsal trunk (Figure 1a). Her forearms
were densely covered by verrucous lesions with the exception of a clear linear
patch on the dorsal aspect of the left forearm (Figure 1b). The perioral area was
notable for white spires projecting from verrucous papules (Figure 1c) while the
oral mucosa and teeth appeared normal on visual examination. The rest of her
body, including the palms and soles, was covered by patchy, scaly lesions of
varying severity.
PMID- 27502265
TI - Four Diseases, Two Associations, One Patient: A Case of Frontal Fibrosing
Alopecia, Lichen Planus Pigmentosus, Acne Rosacea, and Morbihan Disease.
AB - A 77-year-old woman born in the Dominican Republic presented with fullness of the
glabella and medial eyebrows for 1 year followed by alopecia of the lateral
eyebrows and frontal hairline. She stated that although she had a high hairline
at baseline, it had receded in the past year. She had also noted central scalp
hair thinning that started 6 years earlier. She denied all styling practices that
used traction or chemical processes, although she admitted to hair dye and blow
dryer use. She reported "acne" in the central face for decades and darkening of
the skin on the lateral face for several years. Her medical history included
hypertension, hyperlipidemia, hypothyroidism, benign paroxysmal positional
vertigo, and treated breast ductal hyperplasia. Her medications were metoprolol,
amlodipine, aspirin, levothyroxine, omeprazole, pravastatin, and meclizine; she
denied starting any new medications within the past 2 years. Her family history
was notable for androgenic pattern alopecia in a brother and a high hairline in
her father. Review of systems was negative except for knee arthralgias and
seasonal allergic rhinitis.
PMID- 27502266
TI - Epidermal Nevus Presenting in a Pediatric Patient With Pallister-Killian
Syndrome.
AB - A six-year-old boy with Pallister-Killian syndrome (PKS) presented to the clinic
with extensive lesions on his body (Figure 1). The patient was not born with the
lesions but began developing them on the head and neck, extending to his lower
extremities, at 2 years of age. These lesions had been evaluated by his primary
care physician and were previously treated with desonide and ketoconazole cream
with little improvement.
PMID- 27502267
TI - Penile Granuloma Annulare.
AB - A 50-year-old man presented to the genitourinary medicine clinic with a 3-year
history of skin-colored circular papules over the shaft and glans of the penis.
There were multiple lesions that were initially small, around 0.3 cm in diameter,
and gradually enlarged. Physical examination revealed five nodules over the glans
and shaft of the penis, with the largest lesion measuring 3*1 cm over the lateral
aspect of the shaft (Figure 1). There were no similar lesions elsewhere. There
was no lymphadenopathy and the rest of the examination was unremarkable. The
patient complained of discomfort during sexual intercourse but the lesions were
otherwise asymptomatic and nontender. There was no history of trauma to the area
and no dermatological history. He had had the same sexual partner for the past 22
years, no significant medical history, and was not taking any medication. He was
a smoker with a 32-pack-year history. His family history did not include any
dermatological diseases. His father was diagnosed with type II diabetes at 65
years of age and his mother had hypertension since age 60 years. He had consulted
his general practitioner regarding the penile eruption a year earlier and was
treated for a presumed fungal infection with clotrimazole cream for 1 month with
no effect. Results from genitourinary investigations for sexually transmitted
diseases including syphilis were all negative.
PMID- 27502268
TI - Scrotodynia: Diagnostic and Therapeutic Challenge.
AB - Case 1 A 35-year-old married man presented with diffuse burning of the scrotum
for 6 months' duration that was aggravated by sitting and wearing tight-fitting
undergarments. He reported a history of sexual exposure 6 months prior, after
which the complaint started. Clinical examination of the scrotal skin, testis,
epididymis, penis, and perianal area did not reveal any abnormality. Rectal
examination was performed to rule out chronic proctitis. Investigations were
performed to exclude sexually transmitted infections. Ultrasonography of the
abdomen and pelvis was ordered to rule out organic cause. The patient experienced
guilt from the exposure because he was married, and therefore was referred to the
psychiatrist to rule out psychological problems. A diagnosis of major depressive
disorder was made. He was started on amitriptyline 25 mg and was gradually
increased to 50 mg. The patient showed gradual improvement in symptoms after 3
weeks of follow-up.
PMID- 27502269
TI - Facial Blanching After Cosmetic Botulinum Toxin Injection: Case Series.
AB - Case 1 A 32-year-old woman was treated for the first time with onabotulinumtoxinA
(BoNT), receiving 10 units in her forehead and 20 units in her glabella. She
reported no history of skin disease and had a very active lifestyle. She first
noticed blanching while doing a group workout and a friend inquired if she had
"hives" on her forehead (Figure 1). She continued to note the blanching during
workouts 5 months after injection. Each episode lasted 30 minutes to 2 hours.
There were no associated symptoms with the blanching other than minor
embarrassment. Given her active lifestyle and frequent blanching, she has elected
not to receive further injections.
PMID- 27502270
TI - microRNA regulation of neural precursor self-renewal and differentiation.
AB - During early stages of development of the vertebrate central nervous system,
neural precursors divide symmetrically to produce new precursors, thereby
expanding the precursor population. During middle stages of neural development,
precursors switch to an asymmetric division pattern whereby each mitosis produces
one new precursor and one cell that differentiates as a neuron or glial cell. At
late stages of development, most precursors stop dividing and terminally
differentiate. Par complex proteins are associated with the apical membrane of
neural precursors and promote precursor self-renewal. How Par proteins are down
regulated to bring precursor self-renewal to an end has not been known. Our
investigations of zebrafish neural development revealed that the microRNA miR-219
negatively regulates apical Par proteins, thereby promoting cessation of neural
precursor division and driving terminal differentiation.
PMID- 27502271
TI - RNA-sequencing of the sturgeon Acipenser baeri provides insights into expression
dynamics of morphogenic differentiation and developmental regulatory genes in
early versus late developmental stages.
AB - BACKGROUND: Acipenser baeri, one of the critically endangered animals on the
verge of extinction, is a key species for evolutionary, developmental, physiology
and conservation studies and a standout amongst the most important food products
worldwide. Though the transcriptome of the early development of A. baeri has been
published recently, the transcriptome changes occurring in the transition from
embryonic to late stages are still unknown. The aim of this work was to analyze
the transcriptomes of embryonic and post-embryonic stages of A. baeri and
identify differentially expressed genes (DEGs) and their expression patterns
using mRNA collected from specimens at big yolk plug, wide neural plate and 64
day old sturgeon developmental stages for RNA-Seq. RESULTS: The paired-end
sequencing of the transcriptome of samples of A. baeri collected at two early
(big yolk plug (T1, 32 h after fertilization) and wide neural plate formation
(T2, 45 h after fertilization)) and one late (T22, 64 day old sturgeon)
developmental stages using Illumina Hiseq2000 platform generated 64039846,
64635214 and 75293762 clean paired-end reads for T1, T2 and T22, respectively.
After quality control, the sequencing reads were de novo assembled to generate a
set of 149,265 unigenes with N50 value of 1277 bp. Functional annotation
indicated that a substantial number of these unigenes had significant similarity
with proteins in public databases. Differential expression profiling allowed the
identification of 2789, 12,819 and 10,824 DEGs from the respective T1 vs. T2, T1
vs. T22 and T2 vs. T22 comparisons. High correlation of DEGs' features was
recorded among early stages while significant divergences were observed when
comparing the late stage with early stages. GO and KEGG enrichment analyses
revealed the biological processes, cellular component, molecular functions and
metabolic pathways associated with identified DEGs. The qRT-PCR performed for
candidate genes in specimens confirmed the validity of the RNA-seq data.
CONCLUSIONS: This study presents, for the first time, an extensive overview of
RNA-Seq based characterization of the early and post-embryonic developmental
transcriptomes of A. baeri and provided 149,265 gene sequences that will be
potentially valuable for future molecular and genetic studies in A. baeri.
PMID- 27502272
TI - Thresholds and timing of pre-operative thrombocytosis and ovarian cancer
survival: analysis of laboratory measures from electronic medical records.
AB - BACKGROUND: Thrombocytosis has been associated with poor ovarian cancer
prognosis. However, comparisons of thresholds to define thrombocytosis and
evaluation of relevant timing of platelet measurement has not been previously
conducted. METHODS: We selected Tumor Registry confirmed ovarian, primary
peritoneal, and fallopian tube cancer cases diagnosed between 1995-2013 from the
Vanderbilt University Medical Center. Laboratory measured platelet values from
electronic medical records (EMR) were used to determine thrombocytosis at three
thresholds: a platelet count greater than 350, 400, or 450 * 10(9)/liter. Timing
was evaluated with 5 intervals: on the date of diagnosis, and up to 1, 2, 4, and
8 weeks prior to the date of diagnosis. Cox regression was used to calculate
hazard ratios (HR) and confidence intervals (CI) for association with overall
survival; adjustment included age, stage, grade, and histologic subtype of
disease. RESULTS: Pre-diagnosis platelet measures were available for 136, 241,
280, 297, and 304 cases in the five intervals. The prevalence of thrombocytosis
decreased with increasing thresholds and was generally consistent across the five
time intervals, ranging from 44.8-53.2 %, 31.6-39.4 %, and 19.9-26.1 % across the
three thresholds. Associations with higher grade and stage of disease gained
significance as the threshold increased. With the exception of the lowest
threshold on the date of diagnosis (HR350: 1.55, 95 % CI: 0.97-2.47), all other
survival associations were significant, with the highest reaching twice the risk
of death for thrombocytosis on the date of diagnosis (HR400: 2.01, 95 % CI: 1.25
3.23). CONCLUSIONS: Our EMR approach yielded associations comparable to published
findings from medical record abstraction approaches. In addition, our results
indicate that lower thrombocytosis thresholds and platelet measures up to 8 weeks
before diagnosis may inform ovarian cancer characteristics and prognosis.
PMID- 27502274
TI - Molecular Basis for the Protein Recognition Specificity of the Dynein Light Chain
DYNLT1/Tctex1: CHARACTERIZATION OF THE INTERACTION WITH ACTIVIN RECEPTOR IIB.
AB - It has been suggested that DYNLT1, a dynein light chain known to bind to various
cellular and viral proteins, can function both as a molecular clamp and as a
microtubule-cargo adapter. Recent data have shown that the DYNLT1 homodimer binds
to two dynein intermediate chains to subsequently link cargo proteins such as the
guanine nucleotide exchange factor Lfc or the small GTPases RagA and Rab3D.
Although over 20 DYNLT1-interacting proteins have been reported, the exact
sequence requirements that enable their association to the canonical binding
groove or to the secondary site within the DYNLT1 surface are unknown. We
describe herein the sequence recognition properties of the hydrophobic groove of
DYNLT1 known to accommodate dynein intermediate chain. Using a pepscan approach,
we have substituted each amino acid within the interacting peptide for all 20
natural amino acids and identified novel binding sequences. Our data led us to
propose activin receptor IIB as a novel DYNLT1 ligand and suggest that DYNLT1
functions as a molecular dimerization engine bringing together two receptor
monomers in the cytoplasmic side of the membrane. In addition, we provide
evidence regarding a dual binding mode adopted by certain interacting partners
such as Lfc or the parathyroid hormone receptor. Finally, we have used NMR
spectroscopy to obtain the solution structure of human DYNLT1 forming a complex
with dynein intermediate chain of ~74 kDa; it is the first mammalian structure
available.
PMID- 27502273
TI - The Human Ether-a-go-go-related Gene (hERG) Potassium Channel Represents an
Unusual Target for Protease-mediated Damage.
AB - The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of
the rapidly activating delayed rectifier potassium channel (IKr), which is
important for cardiac repolarization. Dysfunction of hERG causes long QT syndrome
and sudden death, which occur in patients with cardiac ischemia. Cardiac ischemia
is also associated with activation, up-regulation, and secretion of various
proteolytic enzymes. Here, using whole-cell patch clamp and Western blotting
analysis, we demonstrate that the hERG/IKr channel was selectively cleaved by the
serine protease, proteinase K (PK). Using molecular biology techniques including
making a chimeric channel between protease-sensitive hERG and insensitive human
ether-a-go-go (hEAG), as well as application of the scorpion toxin BeKm-1, we
identified that the S5-pore linker of hERG is the target domain for proteinase K
cleavage. To investigate the physiological relevance of the unique susceptibility
of hERG to proteases, we show that cardiac ischemia in a rabbit model was
associated with a reduction in mature ERG expression and an increase in the
expression of several proteases, including calpain. Using cell biology
approaches, we found that calpain-1 was actively released into the extracellular
milieu and cleaved hERG at the S5-pore linker. Using protease cleavage-predicting
software and site-directed mutagenesis, we identified that calpain-1 cleaves hERG
at position Gly-603 in the S5-pore linker of hERG. Clarification of protease
mediated damage of hERG extends our understanding of hERG regulation. Damage of
hERG mediated by proteases such as calpain may contribute to ischemia-associated
QT prolongation and sudden cardiac death.
PMID- 27502275
TI - Interdomain Conformational Changes Provide Allosteric Regulation en Route to
Chorismate.
AB - Multifunctional proteins play a variety of roles in metabolism. Here, we examine
the catalytic function of the combined 3-deoxy-d-arabino heptulosonate-7
phosphate synthase (DAH7PS) and chorismate mutase (CM) from Geobacillus sp.
DAH7PS operates at the start of the biosynthetic pathway for aromatic
metabolites, whereas CM operates in a dedicated branch of the pathway for the
biosynthesis of amino acids tyrosine and phenylalanine. In line with sequence
predictions, the two catalytic functions are located in distinct domains, and
these two activities can be separated and retain functionality. For the full
length protein, prephenate, the product of the CM reaction, acts as an allosteric
inhibitor for the DAH7PS. The crystal structure of the full-length protein with
prephenate bound and the accompanying small angle x-ray scattering data reveal
the molecular mechanism of the allostery. Prephenate binding results in the
tighter association between the dimeric CM domains and the tetrameric DAH7PS,
occluding the active site and therefore disrupting DAH7PS function. Acquisition
of a physical gating mechanism to control catalytic function through gene fusion
appears to be a general mechanism for providing allostery for this enzyme.
PMID- 27502276
TI - The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and
Unimmunized BALB/c Mice.
AB - Immunological memory is a fundamental function of vaccination. The antigenic
breakdown products of the vaccine may not persist, and undefined tonic
stimulation has been proposed to maintain the specific memory. We have suggested
that cellular stress agents to which the immune cells are constantly exposed may
be responsible for tonic stimulation. Here we have studied four stress agents:
sodium arsenite, an oxidative agent; Gramicidin, eliciting K(+) efflux and
calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide
(alum), an immunological adjuvant. The aims of this study are to extend these
investigations to T and B cell responses of unimmunized and ovalbumin (OVA)
immunized BALB/c mice, and furthermore, to ascertain whether stress is involved
in optimal expression of memory B cells, as demonstrated in CD4(+) T cells.
Examination of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor)
interaction and the inflammasome pathway defined by the IL-1-IL-1R interaction
between dendritic cells (DC) and CD4(+) T cells suggests that both pathways are
involved in the development of optimal expression of CD4(+)CD45RO(+) memory T
cells in unimmunized and OVA-immunized BALB/c mice. Furthermore, significant
direct correlation was found between CD4(+)CD44(+) memory T cells and both IL-15
of the homeostatic and IL-1beta of the inflammasome pathways. However,
CD19(+)CD27(+) memory B cells in vivo seem to utilize only the IL-15/IL-15R
homeostatic pathway, although the proliferative responses are enhanced by the
stress agents. Altogether, stress agents may up-regulate unimmunized and OVA
immunized CD4(+)CD44(+) memory T cells by the homeostatic and inflammasome
pathways. However, the CD19(+)CD27(+) memory B cells utilize only the homeostatic
pathway.
PMID- 27502277
TI - An ATP Binding Cassette Transporter Mediates the Uptake of alpha-(1,6)-Linked
Dietary Oligosaccharides in Bifidobacterium and Correlates with Competitive
Growth on These Substrates.
AB - The molecular details and impact of oligosaccharide uptake by distinct human gut
microbiota (HGM) are currently not well understood. Non-digestible dietary
galacto- and gluco-alpha-(1,6)-oligosaccharides from legumes and starch,
respectively, are preferentially fermented by mainly bifidobacteria and
lactobacilli in the human gut. Here we show that the solute binding protein
(BlG16BP) associated with an ATP binding cassette (ABC) transporter from the
probiotic Bifidobacterium animalis subsp. lactis Bl-04 binds alpha-(1,6)-linked
glucosides and galactosides of varying size, linkage, and monosaccharide
composition with preference for the trisaccharides raffinose and panose. This
preference is also reflected in the alpha-(1,6)-galactoside uptake profile of the
bacterium. Structures of BlG16BP in complex with raffinose and panose revealed
the basis for the remarkable ligand binding plasticity of BlG16BP, which
recognizes the non-reducing alpha-(1,6)-diglycoside in its ligands. BlG16BP
homologues occur predominantly in bifidobacteria and a few Firmicutes but lack in
other HGMs. Among seven bifidobacterial taxa, only those possessing this
transporter displayed growth on alpha-(1,6)-glycosides. Competition assays
revealed that the dominant HGM commensal Bacteroides ovatus was out-competed by
B. animalis subsp. lactis Bl-04 in mixed cultures growing on raffinose, the
preferred ligand for the BlG16BP. By comparison, B. ovatus mono-cultures grew
very efficiently on this trisaccharide. These findings suggest that the ABC
mediated uptake of raffinose provides an important competitive advantage,
particularly against dominant Bacteroides that lack glycan-specific ABC
transporters. This novel insight highlights the role of glycan transport in
defining the metabolic specialization of gut bacteria.
PMID- 27502278
TI - Outer Membrane Proteins Derived from Non-cyanobacterial Lineage Cover the
Peptidoglycan of Cyanophora paradoxa Cyanelles and Serve as a Cyanelle Diffusion
Channel.
AB - The cyanelle is a primitive chloroplast that contains a peptidoglycan layer
between its inner and outer membranes. Despite the fact that the envelope
structure of the cyanelle is reminiscent of Gram-negative bacteria, the
Cyanophora paradoxa genome appears to lack genes encoding homologs of putative
peptidoglycan-associated outer membrane proteins and outer membrane channels.
These are key components of Gram-negative bacterial membranes, maintaining
structural stability and regulating permeability of outer membrane, respectively.
Here, we discovered and characterized two dominant peptidoglycan-associated outer
membrane proteins of the cyanelle (~2 * 10(6) molecules per cyanelle). We named
these proteins CppF and CppS (cyanelle peptidoglycan-associated proteins). They
are homologous to each other and function as a diffusion channel that allows the
permeation of compounds with Mr <1,000 as revealed by permeability measurements
using proteoliposomes reconstituted with purified CppS and CppF. Unexpectedly,
amino acid sequence analysis revealed no evolutionary linkage to cyanobacteria,
showing only a moderate similarity to cell surface proteins of bacteria belonging
to Planctomycetes phylum. Our findings suggest that the C. paradoxa cyanelle
adopted non-cyanobacterial lineage proteins as its main outer membrane
components, providing a physical link with the underlying peptidoglycan layer and
functioning as a diffusion route for various small substances across the outer
membrane.
PMID- 27502279
TI - Structures of Exopolysaccharides Involved in Receptor-mediated Perception of
Mesorhizobium loti by Lotus japonicus.
AB - In the symbiosis formed between Mesorhizobium loti strain R7A and Lotus japonicus
Gifu, rhizobial exopolysaccharide (EPS) plays an important role in infection
thread formation. Mutants of strain R7A affected in early exopolysaccharide
biosynthetic steps form nitrogen-fixing nodules on L. japonicus Gifu after a
delay, whereas mutants affected in mid or late biosynthetic steps induce
uninfected nodule primordia. Recently, it was shown that a plant receptor-like
kinase, EPR3, binds low molecular mass exopolysaccharide from strain R7A to
regulate bacterial passage through the plant's epidermal cell layer (Kawaharada,
Y., Kelly, S., Nielsen, M. W., Hjuler, C. T., Gysel, K., Muszynski, A., Carlson,
R. W., Thygesen, M. B., Sandal, N., Asmussen, M. H., Vinther, M., Andersen, S.
U., Krusell, L., Thirup, S., Jensen, K. J., et al. (2015) Nature 523, 308-312).
In this work, we define the structure of both high and low molecular mass
exopolysaccharide from R7A. The low molecular mass exopolysaccharide produced by
R7A is a monomer unit of the acetylated octasaccharide with the structure (2,3/3
OAc)beta-d-RibfA-(1->4)-alpha-d-GlcpA-(1->4)-beta-d-Glcp-(1->6)-(3OAc)beta-d-Glcp
(1->6)-*[(2OAc)beta-d-Glcp-(1->4)-(2/3OAc)beta-d-Glcp-(1->4)-beta-d-Glcp-(1->3)
beta-d-Galp]. We propose it is a biosynthetic constituent of high molecular mass
EPS polymer. Every new repeating unit is attached via its reducing-end beta-d
Galp to C-4 of the fourth glucose (asterisked above) of the octasaccharide,
forming a branch. The O-acetylation occurs on the four glycosyl residues in a non
stoichiometric ratio, and each octasaccharide subunit is on average substituted
with three O-acetyl groups. The availability of these structures will facilitate
studies of EPR3 receptor binding of symbiotically compatible and incompatible EPS
and the positive or negative consequences on infection by the M. loti exo mutants
synthesizing such EPS variants.
PMID- 27502280
TI - Tuning the Transcriptional Response to Hypoxia by Inhibiting Hypoxia-inducible
Factor (HIF) Prolyl and Asparaginyl Hydroxylases.
AB - The hypoxia-inducible factor (HIF) system orchestrates cellular responses to
hypoxia in animals. HIF is an alpha/beta-heterodimeric transcription factor that
regulates the expression of hundreds of genes in a tissue context-dependent
manner. The major hypoxia-sensing component of the HIF system involves oxygen
dependent catalysis by the HIF hydroxylases; in humans there are three HIF prolyl
hydroxylases (PHD1-3) and an asparaginyl hydroxylase (factor-inhibiting HIF
(FIH)). PHD catalysis regulates HIFalpha levels, and FIH catalysis regulates HIF
activity. How differences in HIFalpha hydroxylation status relate to variations
in the induction of specific HIF target gene transcription is unknown. We report
studies using small molecule HIF hydroxylase inhibitors that investigate the
extent to which HIF target gene expression is induced by PHD or FIH inhibition.
The results reveal substantial differences in the role of prolyl and asparaginyl
hydroxylation in regulating hypoxia-responsive genes in cells. PHD inhibitors
with different structural scaffolds behave similarly. Under the tested
conditions, a broad-spectrum 2-oxoglutarate dioxygenase inhibitor is a better
mimic of the overall transcriptional response to hypoxia than the selective PHD
inhibitors, consistent with an important role for FIH in the hypoxic
transcriptional response. Indeed, combined application of selective PHD and FIH
inhibitors resulted in the transcriptional induction of a subset of genes not
fully responsive to PHD inhibition alone. Thus, for the therapeutic regulation of
HIF target genes, it is important to consider both PHD and FIH activity, and in
the case of some sets of target genes, simultaneous inhibition of the PHDs and
FIH catalysis may be preferable.
PMID- 27502281
TI - MicroRNA-223-5p and -3p Cooperatively Suppress Necroptosis in Ischemic/Reperfused
Hearts.
AB - Recent studies have shown that myocardial ischemia/reperfusion (I/R)-induced
necrosis can be controlled by multiple genes. In this study, we observed that
both strands (5p and 3p) of miR-223 were remarkably dysregulated in mouse hearts
upon I/R. Precursor miR-223 (pre-miR-223) transgenic mouse hearts exhibited
better recovery of contractile performance over reperfusion period and lesser
degree of myocardial necrosis than wild type hearts upon ex vivo and in vivo
myocardial ischemia. Conversely, pre-miR-223 knock-out (KO) mouse hearts
displayed opposite effects. Furthermore, we found that the RIP1/RIP3/MLKL
necroptotic pathway and inflammatory response were suppressed in transgenic
hearts, whereas they were activated in pre-miR-223 KO hearts upon I/R compared
with wild type controls. Accordingly, treatment of pre-miR-223 KO mice with
necrostatin-1s, a potent necroptosis inhibitor, significantly decreased I/R
triggered cardiac necroptosis, infarction size, and dysfunction. Mechanistically,
we identified two critical cell death receptors, TNFR1 and DR6, as direct targets
of miR-223-5p, whereas miR-223-3p directly suppressed the expression of NLRP3 and
IkappaB kinase alpha, two important mediators known to be involved in I/R-induced
inflammation and cell necroptosis. Our findings indicate that miR-223-5p/-3p
duplex works together and cooperatively inhibits I/R-induced cardiac necroptosis
at multiple layers. Thus, pre-miR-223 may constitute a new therapeutic agent for
the treatment of ischemic heart disease.
PMID- 27502282
TI - Functional Annotation of a Presumed Nitronate Monoxygenase Reveals a New Class of
NADH:Quinone Reductases.
AB - The protein PA1024 from Pseudomonas aeruginosa PAO1 is currently classified as 2
nitropropane dioxygenase, the previous name for nitronate monooxygenase in the
GenBankTM and PDB databases, but the enzyme was not kinetically characterized. In
this study, PA1024 was purified to high levels, and the enzymatic activity was
investigated by spectroscopic and polarographic techniques. Purified PA1024 did
not exhibit nitronate monooxygenase activity; however, it displayed NADH:quinone
reductase and a small NADH:oxidase activity. The enzyme preferred NADH to NADPH
as a reducing substrate. PA1024 could reduce a broad spectrum of quinone
substrates via a Ping Pong Bi Bi steady-state kinetic mechanism, generating the
corresponding hydroquinones. The reductive half-reaction with NADH showed a kred
value of 24 s-1 and an apparent Kd value estimated in the low micromolar range.
The enzyme was not able to reduce the azo dye methyl red, routinely used in the
kinetic characterization of azoreductases. Finally, we revisited and modified the
existing six conserved motifs of PA1024, which define a new class of NADH:quinone
reductases and are present in more than 490 hypothetical proteins in the
GenBankTM, the vast majority of which are currently misannotated as nitronate
monooxygenase.
PMID- 27502283
TI - Rice Endosperm Starch Phosphorylase (Pho1) Assembles with Disproportionating
Enzyme (Dpe1) to Form a Protein Complex That Enhances Synthesis of Malto
oligosaccharides.
AB - Starch synthesis in cereal grain endosperm is dependent on the concerted actions
of many enzymes. The starch plastidial phosphorylase (Pho1) plays an important
role in the initiation of starch synthesis and in the maturation of starch
granule in developing rice seeds. Prior evidence has suggested that the rice
enzyme, OsPho1, may have a physical/functional interaction with other starch
biosynthetic enzymes. Pulldown experiments showed that OsPho1 as well as OsPho1
devoid of its L80 region, a peptide unique to higher plant phosphorylases,
captures disproportionating enzyme (OsDpe1). Interaction of the latter enzyme
form with OsDpe1 indicates that the putative regulatory L80 is not responsible
for multienzyme assembly. This heterotypic enzyme complex, determined at a molar
ratio of 1:1, was validated by reciprocal co-immunoprecipitation studies of
native seed proteins and by co-elution chromatographic and co-migration
electrophoretic patterns of these enzymes in rice seed extracts. The OsPho1
OsDpe1 complex utilized a broader range of substrates for enhanced synthesis of
larger maltooligosaccharides than each individual enzyme and significantly
elevated the substrate affinities of OsPho1 at 30 degrees C. Moreover, the
assembly with OsDpe1 enables OsPho1 to utilize products of transglycosylation
reactions involving G1 and G3, sugars that it cannot catalyze directly.
PMID- 27502284
TI - Result of randomized control trial to increase breast health awareness among
young females in Malaysia.
AB - BACKGROUND: Breast cancer is the most common cancer and the second principal
cause of cancer deaths in women worldwide as well as in Malaysia. Breast self
examination (BSE) has a role in raising breast cancer awareness among women and
educational programs play an important role in breast cancer preventive behavior.
The aim of this study is to develop, implement and evaluate the effectiveness of
Breast Health Awareness program based on health belief model on knowledge of
breast cancer and breast-selfexamination and BSE practice among female students
in Malaysia. METHODS: A single-blind randomized controlled trial was carried out
among 370 female undergraduate students from January 2011 to April 2012 in two
selected public universities in Malaysia. Participants were randomized to either
the intervention group or the control group. The educational program was
delivered to the intervention group. The outcome measures were assessed at
baseline, 6, and 12 months after implementing the health educational program. Chi
square, independent samples t-test and two-way repeated measures ANOVA (GLM) were
conducted in the course of the data analyses. RESULTS: Mean scores of knowledge
on breast cancer (p<0.003), knowledge on breast self examination (p<0.001),
benefits of BSE (p<0.00), barrier of BSE (0.01) and confidence of BSE practice
(p<0.00) in the intervention group had significant differences in comparison with
those of the control group 6 and 12 months after the intervention. Also, among
those who never practiced BSE at baseline, frequency of BSE practice increased 6
and 12 months after the intervention (p<0.05). CONCLUSION: The Breast Health
Awareness program based on health the belief model had a positive effect on
knowledge of breast cancer and breast self-examination and practice of BSE among
females in Malaysia. TRIAL REGISTRATION: The ANZCTR clinical trial registry (
ACTRN12616000831482 ), retrospectively registered on Jun 23, 2016 in
ANZCTR.org.au.
PMID- 27502285
TI - Three new sesquiterpenoids from agarwood of Aquilaria crassna.
AB - Three new sesquiterpenoids (1-3), together with two known ones were isolated from
the EtOAc extract of agarwood originating from Aquilaria crassna. The new
compounds were elucidated on the basis of spectroscopic techniques (UV, IR, MS,
1D and 2D NMR). Compounds 1-5 were isolated from agarwood of A. crassna for the
first time. In the acetylcholinesterase inhibition experiment of 2-5, compound 3
showed acetylcholinesterase inhibition activity (IR 42.9+/-0.6%). Compound 5
expressed antibacterial activities against Staphylococcus aureus and Ralstonia
solanacearum with diameter of the inhibition zones of 12.35+/-0.11mm and 16.90+/
0.09mm, respectively.
PMID- 27502286
TI - Morphology, Clinicopathologic Correlations, and Mechanisms in Heart Valve Health
and Disease.
AB - The clinical and pathological features of the most frequent intrinsic structural
diseases that affect the heart valves are well established, but heart valve
disease mechanisms are poorly understood, and effective treatment options are
evolving. Major advances in the understanding of the structure, function and
biology of native valves and the pathobiology, biomaterials and biomedical
engineering, and the clinical management of valvular heart disease have occurred
over the past several decades. This communication reviews contemporary
considerations relative to the pathology of valvular heart disease, including (1)
clinical significance and epidemiology of valvular heart disease; (2) functional
and dynamic valvular macro-, micro- and ultrastructure; (3) causes, morphology
and mechanisms of human valvular heart disease; and (4) pathologic considerations
in valve replacement, repair and, potentially, regeneration of the heart valves.
PMID- 27502287
TI - Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients
with HCV genotype 1 infection.
AB - BACKGROUND: DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A
inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non
nucleoside NS5B inhibitor), has achieved high rates of sustained virologic
response at post-treatment Week 12 (SVR12) in phase 3 studies. METHODS: In this
phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for
24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 %
genotype 1b). RESULTS: SVR12 rates >=95 % were achieved in both treatment-naive
(N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for
12 weeks and were comparable across patient subgroups, including patients aged
>=65 years and those with cirrhosis. DUAL recipients (N = 75) had an SVR12 rate
of 87 %. In the absence of baseline resistance-associated polymorphisms at
positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among
genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92
%) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse
events, mostly liver related, led to treatment discontinuation in 10 % of DCV
TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who
discontinued before Week 4 and by 12/12 patients who completed >=4 weeks of DCV
TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO
and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to
adverse events. No deaths occurred. CONCLUSION: SVR12 was achieved by 96 % of
Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with
the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.
PMID- 27502289
TI - Erratum to: Concentric Multiple Rings by Droplet Epitaxy: Fabrication and Study
of the Morphological Anisotropy.
PMID- 27502288
TI - Sphingolipids as targets for treatment of fungal infections.
AB - Invasive fungal infections have significantly increased in the last few decades.
Three classes of drugs are commonly used to treat these infections: polyenes,
azoles and echinocandins. Unfortunately each of these drugs has drawbacks;
polyenes are toxic, resistance against azoles is emerging and echinocandins have
narrow spectrum of activity. Thus, the development of new antifungals is urgently
needed. In this context, fungal sphingolipids have emerged as a potential target
for new antifungals, because their biosynthesis in fungi is structurally
different than in mammals. Besides, some fungal sphingolipids play an important
role in the regulation of virulence in a variety of fungi. This review aims to
highlight the diverse strategies that could be used to block the synthesis or/and
function of fungal sphingolipids.
PMID- 27502291
TI - Another piece in the puzzle of bicuspid aortic valve syndrome.
PMID- 27502290
TI - Identification of patients at risk for renal impairment after living donor kidney
transplantation.
AB - PURPOSE: Outcome after living donor kidney transplantation is highly relevant,
since recipient and donor were exposed to notable harm. Reliable identification
of risk factors is necessary. METHODS: Three hundred sixty-six living donor
kidney transplants were included in this observational retrospective study.
Relevant risk factors for renal impairment 1 year after transplantation and
delayed graft function were identified with univariable and multivariable binary
logistic regression and ordinal regression analysis. RESULTS: Eighty-four
patients (26.6 %) suffered from renal impairment KDIGO stage >=4 1 year post
transplant; median estimated glomerular filtration rate was 35.3 ml/min. In
multivariable ordinal regression, male recipient sex (p < 0.001), recipient body
mass index (p = 0.006), donor age (p = 0.002) and high percentages of panel
reactive antibodies (p = 0.021) were revealed as independent risk factors for
higher KDIGO stages. After adjustment for post-transplant data, recipient male
sex (p < 0.001), donor age (p = 0.026) and decreased early renal function at the
first post-transplant outpatient visit (p < 0.001) were identified as independent
risk factors. Delayed graft function was independently associated with long stay
on the waiting list (p = 0.011), high donor body mass index (p = 0.043),
prolonged warm ischemic time (p = 0.016) and the presence of preformed donor
specific antibodies (p = 0.043). CONCLUSIONS: Broadening the donor pool with non
blood related donors seems to be legitimate, although with respect to careful
medical selection, since donor age in combination with male recipient sex were
shown to be risk factors for decreased graft function. Warm ischemic time and
waiting time need to be kept as short as possible to avoid delayed graft
function. Transplantation across HLA and ABO borders did not affect outcome
significantly.
PMID- 27502292
TI - The high-risk criteria low-attenuation plaque <60 HU and the napkin-ring sign are
the most powerful predictors of MACE: a long-term follow-up study.
AB - Aims: To assess the prognostic value of coronary CT angiography (CTA) for
prediction of major adverse cardiac events (MACE) over a long-term follow-up
period. Methods and Results: A total of 1469 low-to-intermediate-risk patients
(65.9 years; 44.2% females) were included in our prospective cohort study. CTA
was evaluated for (i) stenosis severity (minimal <10%; mild <50%; moderate 50
70%; severe >70%), (ii) plaque types (calcified, mixed dominantly calcified,
mixed dominantly non-calcified, non-calcified), and (iii) high-risk plaque
criteria [low-attenuation plaque (LAP) quantified by HU, napkin-ring (NR) sign,
spotty calcification <3 mm, and remodelling index (RI)]. Over a follow-up of mean
7.8 years, MACE rate was 41 (2.8%) and 0% in patients with negative CTA. MACE
rate increased along with stenosis severity by CTA (from 1.3 to 7.8%) (P < 0.001)
and was higher in T3/T4 plaques than in T2/T1 (7.8 vs. 1.9%; P < 0.0001). LAP
density was lower (35.2 HU +/- 32 vs. 108.8 HU +/- 53) (P < 0.001) and both NR
sign prevalence with n = 26 (63.4%) vs. n = 40 (28%) and LAP <30, <60, and <90 HU
prevalence with 46.3-78% vs. 2.4-7% were higher in the MACE group (P < 0.001). On
univariate and unadjusted multivariable proportional Hazards model, LAP <60 HU
and NR were the strongest MACE predictors (HR 4.96; 95% CI: 2.0-12.2 and HR 3.85;
95% CI: 1.7-8.6) (P < 0.0001), while spotty calcification (HR 2.2; 95% CI: 1.1
4.3, P < 0.001), stenosis severity, and plaque type (HR 1.5; 95% CI: 1.1-2.3 and
HR 1.7; 95% CI: 1.1-2.6) (P < 0.001) were less powerful. After adjusting for risk
factors, CTA stenosis severity, and plaque type, LAP <60 HU and the NR sign
remained significant (P < 0.001), while the effect of NR sign was even enhancing.
HRP criteria were independent predictors from other risk factors. Conclusion:
Prognosis is excellent over a long-term period if CTA is negative and worsening
with an increasing non-calcifying plaque component. LAP <60 HU and NR sign are
the most powerful MACE predictors.
PMID- 27502293
TI - Quantitative assessment of the entire right ventricle from one acoustic window:
an attractive approach.
AB - Aims: The aim of this prospective study was to evaluate the feasibility and
establish normal values of functional right ventricle (RV) parameters as assessed
in our four, long-axis view RV model using iRotate echocardiography. Furthermore,
we evaluated the potential use of this model in patients with abnormally loaded
RVs. Method and results: One hundred and fifty-five healthy subjects aged 20-72
years (>=28 subjects per decile) were prospectively recruited. We used non
dedicated RV speckle-tracking software to test the feasibility and to establish
normal range values of peak systolic global longitudinal RV strain (RV-GLS) from
the RV free-walls (septum was excluded). Also normal range values for:
dimensions, tricuspid annular plane systolic excursion (TAPSE) and tricuspid
annular peak systolic velocity (TDI-S') were established. The feasibility of RV
GLS was 88, 84, and 62%, respectively, in the lateral, inferior, and anterior
free wall. Mean RV-GLS normal values were -24.5 +/- 4.9% for lateral wall and
25.4 +/- 5.0% for anterior wall. Mean RV-GLS in the inferior wall was -23.2 +/-
4.4% in the aortic (Ao) view and -20.7 +/- 5.0% in the coronal (CV) view. The
feasibility of mean RV-GLS was 100% in the anterior, lateral, and inferior walls
in abnormally dilated RVs. Conclusion: The feasibility of all RV parameters
assessed in the four-view iRotate model is good to excellent. Normal values for
RV dimension and function of the anterior, inferior, and lateral RV walls have
been established. Further studies and dedicated RV speckle-tracking software are
warranted to discover the full potential of this new technique.
PMID- 27502294
TI - Predicting outcomes after percutaneous mitral balloon valvotomy: the impact of
left ventricular strain imaging.
AB - Aims: This study aimed (1) to evaluate the impact of preprocedural two
dimensional speckle-tracking echocardiography (2D-STE) on long-term outcome after
successful percutaneous mitral balloon valvotomy (PMBV) in patients with mitral
stenosis (MS) and (2) to determine whether 2D-STE detects underlying diastolic
dysfunction as defined by invasive haemodynamic study. Methods and Results: Sixty
four consecutive MS patients with preserved left ventricular ejection fraction
(LVEF >=50%) and who underwent successfully PMBV were studied. Successful
immediate result was defined as post-procedural mitral valve area >=1.5 cm2 and
<=2/4 mitral regurgitation by catheterization. During a follow-up of 4.2 +/- 3.0
years, there were 7 deaths (11%) and 21 late mitral valve reintervention (33%).
Univariate predictors of death were global longitudinal strain (GLS), age, LVEF,
and pre- and post-procedural pulmonary artery pressures. In the multivariate Cox
model, GLS was the strongest predictor of death [hazard ratio (HR) (95% CI), 1.45
(1.07-2.04); P= 0.01]. For the composite endpoint, GLS and post-procedural left
atrial pressure (LAP) were univariate predictors of death or reintervention. At
multivariable analysis, GLS and post-procedural LAP remained in the final model
with strong trend towards significance [GLS HR (95% CI), 1.17 (0.99-1.37); P=
0.056]. There was no correlation between diastolic dysfunction identified at
catheterization and standard echocardiographic and 2D-STE indexes, even after
adjustments for age, left ventricular mass, effective arterial elastance
(afterload), and end-diastolic volume indexes (preload). Conclusion: GLS is a
powerful predictor of long-term outcome after successful PMBV and provides
incremental prognostic value over traditional parameters. Echocardiographic
diagnosis of concomitant diastolic dysfunction in MS patients remains elusive.
PMID- 27502295
TI - The additive prognostic value of coronary flow velocity reserve during exercise
echocardiography.
AB - Aims: The aim of the study was to assess the additive prognostic value of
coronary flow velocity reserve (CFVR) alongside wall motion analysis during
exercise echocardiography in patients with known or suspected coronary artery
disease (CAD). Methods and results: In a prospective, single-centre,
observational study, we evaluated 689 patients (449 males; 56 + 9 years) who
underwent supine bicycle stress echo (ESE) with CFVR evaluation of the left
anterior descending artery (LAD) by Doppler. ESE was positive for regional wall
motion abnormalities in 359 (52%) patients. Mean CFVR was 1.9 +/- 0.8. During a
median follow-up of 36.6 months, there were 200 patients with major adverse
cardiac events (MACE): 15 deaths, 17 non-fatal myocardial infarctions [11 of them
also had percutaneous coronary intervention with stenting (PCI) or/and coronary
artery bypass graft surgery (CABG)] and 179 patients underwent revascularization.
The 37 months' event-free survival showed the best outcome for those patients
with negative ESE by wall motion criteria and normal CFVR, and the worst outcome
for patients with positive ESE by wall motion and abnormal CVFR (99 vs. 42%, P <
0.0001). At multivariable analysis, CFVR in LAD (OR 0.53, 95% CI 0.35-0.79, P <
0.0001), positivity for regional wall motion abnormalities during testing (OR
0.10, 95% CI 0.04-0.25, P < 0.000), previous PCI (OR 0.38, 95% CI 0.16-0.90, P <
0.003), male sex (OR 0.44, 95% CI 0.27-0.71, P < 0.0009), and heart rate reached
during exercise (OR 0.98, 95% CI 0.96-0.99, P < 0.02) were independent prognostic
predictors of MACE. Conclusion: In patients with known or suspected CAD, exercise
stress tests measuring wall motion criteria and CFVR are additive and
complementary for the identification of patients at risk of experiencing major
adverse events.
PMID- 27502296
TI - Robust phase retrieval for high resolution edge illumination x-ray phase-contrast
computed tomography in non-ideal environments.
AB - Edge illumination x-ray phase contrast tomography is a recently developed imaging
technique which enables three-dimensional visualisation of low-absorbing
materials. Dedicated phase retrieval algorithms can provide separate computed
tomography (CT) maps of sample absorption, refraction and scattering properties.
In this paper we propose a novel "modified local retrieval" method which is
capable of accurately retrieving sample properties in a range of realistic, non
ideal imaging environments. These include system misalignment, defects in the
used optical elements and system geometry variations over time due to vibrations
or temperature fluctuations. System instabilities were analysed, modelled and
incorporated into a simulation study. As a result, an additional modification was
introduced to the retrieval procedure to account for changes in the imaging
system over time, as well as local variations over the field of view. The
performance of the proposed method was evaluated in comparison to a previously
used "global retrieval" method by applying both approaches to experimental CT
data of a rat's heart acquired in a non-ideal environment. The use of the
proposed method resulted in the removal of major artefacts, leading to a
significant improvement in image quality. This method will therefore enable
acquiring high-resolution, reliable CT data of large samples in realistic
settings.
PMID- 27502298
TI - Non-Alzheimer Dementias.
PMID- 27502297
TI - beta-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in
patients with psoriasis.
AB - BACKGROUND: IL-17A is a key driver of human autoimmune diseases, particularly
psoriasis. OBJECTIVE: We sought to determine the role of IL-17A in psoriasis
pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven
pathology. METHODS: We studied 8 healthy subjects and 8 patients with psoriasis
before and after administration of secukinumab, a fully human anti-IL-17A mAb,
and used a combination of classical techniques and a novel skin microperfusion
assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and
lesional skin. For validation, we also tested stored sera from 601 patients with
a variety of autoimmune diseases. RESULTS: IL-17A was specifically expressed in
lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001).
Proteomic and gene transcription analyses revealed dysregulated antimicrobial
peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of
which returned to normal after treatment with secukinumab. beta-Defensin 2 (BD-2)
was identified as a biomarker of IL-17A-driven pathology by comparing protein
expression in patients with psoriasis versus that in healthy subjects (5746 vs 82
pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001),
responsiveness to secukinumab therapy, and synergistic induction by IL-17A and
TNF-alpha in epidermal keratinocytes. In a validation set of sera from 601
patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2
levels are most highly increased in patients with psoriatic skin lesions, and in
patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r =
0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores (r = 0.53,
n = 281, P < .001). CONCLUSION: IL-17A is a primary driver of skin pathology in
patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL
17A-driven skin pathology.
PMID- 27502299
TI - Revisiting DLB Diagnosis: A Consideration of Prodromal DLB and of the Diagnostic
Overlap With Alzheimer Disease.
AB - Efforts to clinically diagnose cases having dementia with Lewy bodies (DLB)
identify those with a characteristic clinical syndrome (probable DLB) at the
expense of missing an equal, if not greater, number of cases who have atypical
presentations thought to be associated with coexisting Alzheimer pathologies.
This article argues that further efforts should now be made to characterize this
atypical group that constitutes cases previously identified postmortem as the
Lewy body variant of Alzheimer disease (AD) or as AD with Lewy bodies. Since such
fine distinction is unlikely to be achieved on clinical grounds alone, this new
diagnostic category will require robust biomarker validation. Turning to a
consideration of early/prodromal diagnosis of both typical and atypical DLB
cases, it is suggested that there will be at least 3 prototypical forms-a mild
cognitive impairment variant, associated with early visuoperceptual and
attentional deficits; a delirium onset DLB with provoked or spontaneous delirium
as the presenting features; and a psychiatric disorder DLB with its primary
presentation as a late-onset affective disorder or psychosis.
PMID- 27502300
TI - Imaging in Dementia With Lewy Bodies: An Overview.
AB - Dementia with Lewy bodies (DLB) while common in older age can present a
diagnostic challenge to clinicians and is often misdiagnosed as Alzheimer disease
(AD). Imaging studies have improved our understanding of the neurobiological
changes in DLB during life and how they differ from AD. This has led to
significant advances in the development of new techniques, such as dopaminergic
imaging, which can aid the clinical diagnosis. Other functional imaging methods
also show promise in helping to assess the influence of differing pathologies in
DLB, most notably, AD-related and vascular pathology during life. This article
will provide an overview of the main imaging findings in DLB.
PMID- 27502301
TI - Parkinson Disease and Dementia.
AB - Dementia is a frequent complication of Parkinson disease (PD) with a yearly
incidence of around 10% of patients with PD. Lewy body pathology is the most
important factor in the development of Parkinson disease dementia (PDD) and there
is evidence for a synergistic effect with beta-amyloid. The clinical phenotype in
PDD extends beyond the dysexecutive syndrome that is often present in early PD
and encompasses deficits in recognition memory, attention, and visual perception.
Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are
often present. This review provides an update on current knowledge of PDD
including aspects of epidemiology, pathology, clinical presentation, management,
and prognosis.
PMID- 27502302
TI - Frontotemporal Dementia: An Updated Clinician's Guide.
AB - Today, frontotemporal dementia (FTD) remains one of the most common forms of
early-onset dementia, that is, before the age of 65, thus posing several
diagnostic challenges to clinicians since symptoms are often mistaken for
psychiatric or neurological diseases causing a delay in correct diagnosis, and
the majority of patients with FTD present with symptoms at ages between 50 and
60. Genetic components are established risk factors for FTD, but the influence of
lifestyle, comorbidity, and environmental factors on the risk of FTD is still
unclear. Approximately 40% of individuals with FTD have a family history of
dementia but less than 10% have a clear autosomal dominant pattern of
inheritance. Lack of insight is often an early clue to FTD. A tailored treatment
option at an early phase can mitigate suffering and improve patients' and
caregivers' quality of life.
PMID- 27502303
TI - Update on Vascular Dementia.
AB - Vascular dementia (VaD) is a major contributor to the dementia syndrome and is
described as having problems with reasoning, planning, judgment, and memory
caused by impaired blood flow to the brain and damage to the blood vessels
resulting from events such as stroke. There are a variety of etiologies that
contribute to the development of vascular cognitive impairment and VaD, and these
are often associated with other dementia-related pathologies such as Alzheimer
disease. The diagnosis of VaD is difficult due to the number and types of lesions
and their locations in the brain. Factors that increase the risk of vascular
diseases such as stroke, high blood pressure, high cholesterol, and smoking also
raise the risk of VaD. Therefore, controlling these risk factors can help lower
the chances of developing VaD. This update describes the subtypes of VaD, with
details of their complex presentation, associated pathological lesions, and
issues with diagnosis, prevention, and treatment.
PMID- 27502304
TI - Erratum to: Therapeutic dilemmas in Hashimoto's encephalopathy.
PMID- 27502305
TI - Overexpression of Antimicrobial, Anticancer, and Transmembrane Peptides in
Escherichia coli through a Calmodulin-Peptide Fusion System.
AB - In recent years, the increasing number of antibiotic-resistant bacteria has
become a serious health concern. Antimicrobial peptides (AMPs) are an important
component of the innate immune system of most organisms. A better understanding
of their structures and mechanisms of action would lead to the design of more
potent and safer AMPs as alternatives for current antibiotics. For detailed
investigations, effective recombinant production which allows the facile
modification of the amino acid sequence, the introduction of unnatural amino
acids, and labeling with stable isotopes for nuclear magnetic resonance (NMR)
studies is desired. Several expression strategies have been introduced in
previous reports; however, their effectiveness has been limited to a select few
AMPs. Here, we have studied calmodulin (CaM) as a more universal carrier protein
to express many types of AMPs in E. coli. We have discovered that the unique
architecture of CaM, consisting of two independent target binding domains with
malleable methionine-rich interaction surfaces, can accommodate numerous amino
acid sequences containing basic and hydrophobic residues. This effectively masks
the toxic antimicrobial activities of many amphipathic AMPs and protects them
from degradation during expression and purification. Here, we demonstrate the
expression of various AMPs using a CaM-fusion expression system, including
melittin, fowlicidin-1, tritrpticin, indolicidin, puroindoline A peptide,
magainin II F5W, lactoferrampin B, MIP3alpha51-70, and human beta-defensin 3 (HBD
3), the latter requiring three disulfide bonds for proper folding. In addition,
our approach was extended to the transmembrane domain of the cell adhesion
protein l-selectin. We propose the use of the CaM-fusion system as a universal
approach to express many cationic amphipathic peptides that are normally toxic
and would kill the bacterial host cells.
PMID- 27502306
TI - Curcumin attenuates osteogenic differentiation and calcification of rat vascular
smooth muscle cells.
AB - Vascular calcification has been considered as a biological process resembling
bone formation involving osteogenic differentiation. It is a major risk factor
for cardiovascular morbidity and mortality. Previous studies have shown the
protective effects of curcumin on cardiovascular diseases. However, whether
curcumin has effects on osteogenic differentiation and calcification of vascular
smooth muscle cells (VSMCs) has not been reported. In the present study, we used
an in vitro model of VSMC calcification to investigate the role of curcumin in
the progression of rat VSMC calcification. Curcumin treatment significantly
reduced calcification of VSMCs in a dose-dependent manner, detected by alizarin
red staining and calcium content assay. Similarly, ALP activity and expression of
bone-related molecules including Runx2, BMP2, and Osterix were also decreased in
VSMCs treated with curcumin. In addition, flow cytometry analysis and caspase-3
activity assay revealed that curcumin treatment significantly suppressed
apoptosis of VSMCs, which plays an important role during vascular calcification.
Furthermore, we found that pro-apoptotic molecules including p-JNK and Bax were
up-regulated in VSMCs treated with calcifying medium, but they were reduced in
VSMCs after curcumin treatment. However, curcumin treatment has no effect on
expression of NF-kappaB p65. Taken together, these findings suggest that curcumin
attenuates apoptosis and calcification of VSMCs, presumably via inhibition of
JNK/Bax signaling pathway.
PMID- 27502307
TI - Randomized trial assessing the safety and efficacy of sitagliptin in Chinese
patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea
alone or combined with metformin.
AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a significant burden in China,
where approximately 114 million patients have been diagnosed with diabetes.
Chinese patients present with prominent beta-cell failure, with resulting
deficiency in insulin secretion, particularly early phase insulin secretion
leading to postprandial hyperglycemia. Sitagliptin, a selective once-daily oral
dipeptidyl peptidase-4 inhibitor, has been shown to improve glycemic control as
monotherapy and in combination with other antihyperglycemic agents, including
sulfonylureas and metformin. METHODS: This was a multicenter randomized double
blind placebo-controlled study conducted in China. The study assessed the safety
and efficacy of the addition of sitagliptin 100 mg once daily versus placebo on
changes from baseline at Week 24 in HbA1c, fasting plasma glucose (FPG) and 2-h
post-meal glucose (PMG). Patients were aged 18-79 years, had T2DM with inadequate
glycemic control, and were taking a sulfonylurea, with or without metformin.
RESULTS: After 24 weeks, sitagliptin reduced HbA1c, FPG, and 2-h PMG
significantly more than placebo (between-treatment differences: -0.61 %, -16.8
mg/dL, and -32.9 mg/dL, respectively; P < 0.001 for all). The addition of
sitagliptin was generally well tolerated, with a comparable incidence of adverse
events and drug-related adverse events in both treatment groups. The sitagliptin
group had a higher incidence of symptomatic hypoglycemia than the placebo group
(25/248 [10.1 %] vs 13/249 [5.2 %], respectively; P = 0.042). CONCLUSIONS:
Sitagliptin 100 mg once daily significantly improved glycemic control in Chinese
patients with T2DM who had inadequate glycemic control with sulfonylurea, with or
without metformin therapy. The addition of sitagliptin was generally well
tolerated. (clinicaltrials.gov: NCT01590771).
PMID- 27502308
TI - USING EXPERT OPINION IN HEALTH TECHNOLOGY ASSESSMENT: A GUIDELINE REVIEW.
AB - OBJECTIVES: External experts can be consulted at different stages of an HTA. When
using vague information sources, it is particularly important to plan, analyze,
and report the information processing in a standardized and transparent way. Our
objective was to search and analyze recommendations regarding where and how to
include expert data in HTA. METHODS: We performed a systematic database search
and screened the Internet pages of seventy-seven HTA organizations for
guidelines, recommendations, and methods papers that address the inclusion of
experts in HTA. Relevant documents were downloaded, and information was extracted
in a standard form. Results were merged in tables and narrative evidence
synthesis. RESULTS: From twenty-two HTA organizations, we included forty-two
documents that consider the use of expert opinion in HTA. Nearly all documents
mention experts in the step of preparation of the evidence report. Six documents
address their role for priority setting of topics, fifteen for scoping, twelve
for the appraisal of evidence and results, another twelve documents mention
experts when considering the dissemination of HTA results. During the assessment
step, experts are most often asked to amend the literature search or to provide
expertise for special data analyses. Another issue for external experts is to
appraise the HTA results and refer them back to a clinical and social context.
Little is reported on methods of expert elicitation when their input substitutes
study data. CONCLUSIONS: Despite existing recommendations on the use of expert
opinion in HTA, common standards for elicitation are scarce in HTA guidelines.
PMID- 27502309
TI - Metabolic Surgery Enters the T2DM Treatment Algorithm.
AB - A Joint Statement endorsed by 45 international organizations, clinicians, and
researchers indicating when to recommend or consider metabolic surgery in type 2
diabetes mellitus (T2DM) treatment has been recently published. These new
guidelines, resulting from the Second Diabetes Surgery Summit (DSS-II), represent
the most radical change in T2DM management of the past few decades.
PMID- 27502310
TI - Typing concordance between PowerPlex(r) Fusion and GlobalFiler(r) based on 1501
Japanese individuals and the causes of typing discrepancies.
PMID- 27502311
TI - Duration of oral tetracycline-class antibiotic therapy and use of topical
retinoids for the treatment of acne among general practitioners (GP): A
retrospective cohort study.
AB - BACKGROUND: Guidelines recommend limiting the duration of oral antibiotic therapy
in acne to 3 to 6 months and prescribing concomitant topical retinoids for all
patients. OBJECTIVE: We sought to evaluate the duration of therapy with oral
tetracyclines and the use of topical retinoids among patients with acne treated
primarily by general practitioners in the United Kingdom. METHODS: We conducted a
retrospective cohort study using the Health Improvement Network database.
RESULTS: The mean duration of therapy was 175.1 days. Of antibiotic courses, 62%
were not associated with a topical retinoid; 29% exceeded 6 months in duration.
If all regions were to achieve uses similar to the region with the shortest mean
duration of therapy, approximately 3.3 million antibiotic days per year could be
avoided in the United Kingdom. LIMITATIONS: The Health Improvement Network does
not include information on acne severity and clinical outcomes. CONCLUSIONS:
Prescribing behavior for oral antibiotics in the treatment of acne among general
practitioners is not aligned with current guideline recommendations. Increasing
the use of topical retinoids and considering alternative agents to oral
antibiotics when appropriate represent opportunities to reduce antibiotic
exposure and associated complications such as antibiotic resistance and to
improve outcomes in patients treated for acne.
PMID- 27502312
TI - Imaging mass spectrometry assists in the classification of diagnostically
challenging atypical Spitzoid neoplasms.
AB - BACKGROUND: Previously, using imaging mass spectrometry (IMS), we discovered
proteomic differences between Spitz nevi and Spitzoid melanomas. OBJECTIVE: We
sought to determine whether IMS can assist in the classification of
diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and
correlate the IMS and histopathological diagnoses with clinical behavior.
METHODS: We conducted a retrospective collaborative study involving centers from
11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were
divided into clinical groups 1 to 4 representing best to worst clinical behavior.
The association among IMS findings, histopathological diagnoses, and clinical
groups was assessed. RESULTS: There was a strong association between a diagnosis
of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and
4 (recurrence of disease, metastases, or death) compared with clinical group 1
(no recurrence or metastasis beyond a sentinel node) (P < .0001). Older age and
greater tumor thickness were strongly associated with poorer outcome (P = .01).
CONCLUSIONS: IMS diagnosis of ASN better predicted clinical outcome than
histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated
with aggressive clinical behavior. IMS analysis using a proteomic signature may
improve the diagnosis and prediction of outcome/risk stratification for patients
with ASN.
PMID- 27502314
TI - Polydiacetylenyl beta-cyclodextrin based smart vesicles for colorimetric assay of
arginine and lysine.
AB - Selective visualization of arginine and lysine has been explored among 20 amino
acids using the hybrid conjugate of beta-cyclodextrin (beta-CD) and
polydiacetylene (PDA). The mono pentacosa-10,12-diynyl aminomethyl group was
successfully coupled to either the primary or the secondary face of beta-CD,
where mono-6-amino-6-deoxy-beta-CD or mono-3-amino-3-deoxy-beta-CD reacted with
the N-hydroxysuccinimide ester of 10,12-pentacosadiynoic acid. In this
combinatorial system, the cylindrical beta-cyclodextrin functions as a channel
for the introduction of the cationic amino acids to the artificial membrane. The
membrane perturbation and aggregation by the target amino acids could be
exclusively visualized as a blue to red color change based on the responsive
polydiacetylene domain. These interesting findings demonstrated that the
developed beta-CD conjugated PDA system may offer a new method of cell
penetrating mechanism, a promising vector system, as well as impact the
production industry of arginine or lysine.
PMID- 27502315
TI - Usefulness of peripheral arterial signs in the evaluation of aortic
regurgitation.
AB - BACKGROUND: Early diagnosis and optimal timing of surgical repair for chronic
aortic regurgitation (AR) are topics of interest, because left ventricular
compensation delays the clinical signs of the early stages of left ventricular
dysfunction. Various physical signs have been described as indicators of chronic
AR, but AR screening can be difficult depending on the proficiency of primary
care providers. The recent use of the cardio-ankle vascular index (CAVI)
measurement to assess peripheral atherosclerosis may detect AR objectively and
simply because its arterial pulse wave configuration is closely related to the
physical signs of AR. METHODS: CAVI measurements include pulse pressure (PP), the
difference in blood pressures between upper and lower limbs (ABD), ankle-brachial
index (ABI), ejection time (ET), and upstroke time (UT). We evaluated the
differences in CAVI parameters between AR group and age-matched control group,
the relationships between CAVI parameters and the echocardiographic semi
quantitative measurements of AR severity such as left ventricular dimensions (Dd,
Ds) and vena contracta (VC), and between the changes in CAVI parameters before
and after aortic valve replacement. RESULTS: ABD, PP, ET, ankle systolic pressure
and ABI in the AR group were significantly higher than that in the control group.
Brachial diastolic pressure and CAVI in the AR group were significantly lower
than that in the control group. UT was lower than that in the control group
(p=0.05). PP did not correlate with the semi-quantitative AR severity, but ABD
was correlated with Dd, Ds, and VC and was negatively correlated with UT. The
exaggerated ABD, PP, ET, and ABI were moderated after surgery. CONCLUSIONS: CAVI
parameters could be useful in the screening and serial follow-up of AR patients.
PMID- 27502316
TI - Safety and efficacy of direct oral anticoagulants over warfarin in Japanese
patients with acute venous thromboembolism: A meta-analysis.
AB - BACKGROUND: Direct oral anticoagulants (DOACs) have been developed as
alternatives to conventional therapy with warfarin for the treatment of acute
venous thromboembolism (VTE) events. The safety and efficacy of DOACs in Japanese
patients with acute VTE has been investigated in small trials or subgroups from
global randomized controlled trials (RCTs). METHODS AND RESULTS: We conducted a
systematic review and meta-analysis of RCTs, to compare the safety and efficacy
of DOACs to those of conventional therapy in Japanese patients with acute VTE.
Published research was systematically searched for RCTs that compared DOAC to
conventional therapy in Japanese patients with acute VTE. Random-effects models
were used to pool safety and efficacy data across RCTs. Three studies, including
386 patients, were identified. Patients randomized to DOAC had a decreased risk
for all bleeding [risk ratio (RR) 0.69, 95% confidential interval (CI) 0.50
0.95], without any significant differences in recurrent VTE (RR 0.84, 95% CI 0.29
2.43) and recurrent VTE/all-cause death (RR 0.60, 95% CI 0.23-1.56). CONCLUSION:
DOACs offer clinical benefit over conventional therapy in Japanese patients with
acute VTE, showing a significant difference in their bleeding profile.
PMID- 27502317
TI - Adaptive evolution of virus-sensing toll-like receptor 8 in bats.
AB - Recently, bats have gained attention as potential reservoir hosts for emerging
zoonotic single-stranded (ssRNA) viruses that may prove fatal for humans and
other mammals. It has been hypothesized that some features of their innate immune
system may enable bats to trigger an efficient early immune response. Toll-like
receptors (TLRs) represent a first line defense within the innate immune system
and lie directly at the host-pathogen interface in targeting specific microbe
molecular patterns. However, the direction and strength of selection acting on
TLRs are largely unknown for bats. Here, we studied the selection on viral ssRNA
sensing TLR8 based on sequence data of 21 bat species. The major part (63 %) of
the TLR8 gene evolved under purifying selection, likely due to functional
constraints. We also found evidence for persistent positive selection acting on
specific amino acid sites (7 %), especially when compared to viral TLR evolution
of other mammals. All of these putatively positively selected codons were located
in the ligand-binding ectodomain, some coincidenced or were in close proximity to
functional sites, as suggested by the crystallographic structure of the human
TLR8. This might contribute to the inter-species variation in the ability to
recognize molecular patterns of viruses. TLR8 evolution within bats revealed that
branches leading to ancestral and recent lineages evolved under episodic positive
selection, indicating selective selection pressures in restricted bat lineages.
Altogether, we found that the TLR8 displays extensive sequence variation within
bats and that unique features separate them from humans and other mammals.
PMID- 27502313
TI - Clinical outcomes and response of patients applying topical therapy for pyoderma
gangrenosum: A prospective cohort study.
AB - BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited
evidence base for treatment. OBJECTIVE: We sought to estimate the effectiveness
of topical therapies in the treatment of patients with PG. METHODS: This was a
prospective cohort study of UK secondary care patients with a clinical diagnosis
of PG that was suitable for topical treatment (recruited between July 2009 and
June 2012). Participants received topical therapy after normal clinical practice
(primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%).
The primary outcome was speed of healing at 6 weeks. Secondary outcomes included
the following: proportion healed by 6 months; time to healing; global assessment;
inflammation; pain; quality of life; treatment failure; and recurrence. RESULTS:
Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate
0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers
healed by 6 months. The median time to healing was 145 days (95% confidence
interval, 96 days to infinity). Initial ulcer size was a significant predictor of
time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P =
.043). Four patients (15%) had a recurrence. LIMITATIONS: Our study did not
include a randomized comparator. CONCLUSION: Topical therapy is potentially an
effective first-line treatment for PG that avoids the possible side effects
associated with systemic therapy. It remains unclear whether more severe disease
will respond adequately to topical therapy alone.
PMID- 27502319
TI - Emergent spin-valley-orbital physics by spontaneous parity breaking.
AB - The spin-orbit coupling in the absence of spatial inversion symmetry plays an
important role in realizing intriguing electronic states in solids, such as
topological insulators and unconventional superconductivity. Usually, the
inversion symmetry breaking is inherent in the lattice structures, and hence, it
is not easy to control these interesting properties by external parameters. We
here theoretically investigate the possibility of generating the spin-orbital
entanglement by spontaneous electronic ordering caused by electron correlations.
In particular, we focus on the centrosymmetric lattices with local asymmetry at
the lattice sites, e.g. zigzag, honeycomb, and diamond structures. In such
systems, conventional staggered orders, such as charge order and
antiferromagnetic order, break the inversion symmetry and activate the
antisymmetric spin-orbit coupling, which is hidden in a sublattice-dependent form
in the paramagnetic state. Considering a minimal two-orbital model on a honeycomb
structure, we scrutinize the explicit form of the antisymmetric spin-orbit
coupling for all the possible staggered charge, spin, orbital, and spin-orbital
orders. We show that the complete table is useful for understanding of spin
valley-orbital physics, such as spin and valley splitting in the electronic band
structure and generalized magnetoelectric responses in not only spin but also
orbital and spin-orbital channels, reflecting in peculiar magnetic, elastic, and
optical properties in solids.
PMID- 27502320
TI - Erratum to: KSC-N: Clustering of Hierarchical Time Profile Data.
PMID- 27502321
TI - Midrefractive Dielectric Modulator for Broadband Unidirectional Scattering and
Effective Radiative Tailoring in the Visible Region.
AB - Nanoantennas have found many applications in ultrasmall sensors, single-molecule
detection, and all-optical communication. Conventional nanoantennas are based on
noble-metal plasmonic structures, but suffer from large ohmic loss and only
possess dipolar plasmon modes. This has driven an intense search for all
dielectric materials beyond noble metals. Here, we propose midrefractive
nanospheres as a novel all-dielectric material to realize broadband
unidirectional radiation and effective radiative tailoring in the visible region.
Midrefractive all-dielectric materials such as boron nanospheres possess broad
and overlapping electric and magnetic dipole modes. The internal interaction
between these two modes can route the radiation almost on the one side covering
the whole visible range. Unlike the elaborate design in plasmonic nanostructures
to obtain strong coupled broad and narrow modes, the bright mode in boron
nanospheres is intrinsic, independent, and easily coupled with adjacent narrow
modes. So the strong interaction in boron-based heterodimer is able to realize an
independent and precise tailoring of the radiant and subradiant states by simply
changing the particle sizes, respectively. Our findings imply midrefractivity
materials like boron are excellent building blocks to support electromagnetic
coupling operation in nanoscale devices, which will lead to a variety of emerging
applications such as nanoantennas with directing exciton emission, ultrasensitive
nanosensors, or even potential new construction of photonic metamaterials.
PMID- 27502318
TI - Donor-unrestricted T cells in the human CD1 system.
AB - The CD1 and MHC systems are specialized for lipid and peptide display,
respectively. Here, we review evidence showing how cellular CD1a, CD1b, CD1c, and
CD1d proteins capture and display many cellular lipids to T cell receptors
(TCRs). Increasing evidence shows that CD1-reactive T cells operate outside two
classical immunogenetic concepts derived from the MHC paradigm. First, because
CD1 proteins are non-polymorphic in human populations, T cell responses are not
restricted to the donor's genetic background. Second, the simplified population
genetics of CD1 antigen-presenting molecules can lead to simplified patterns of
TCR usage. As contrasted with donor-restricted patterns of MHC-TCR interaction,
the donor-unrestricted nature of CD1-TCR interactions raises the prospect that
lipid agonists and antagonists of T cells could be developed.
PMID- 27502322
TI - In-Depth Characterization and Validation of Human Urine Metabolomes Reveal Novel
Metabolic Signatures of Lower Urinary Tract Symptoms.
AB - Lower urinary tract symptoms (LUTS) are a range of irritative or obstructive
symptoms that commonly afflict aging population. The diagnosis is mostly based on
patient-reported symptoms, and current medication often fails to completely
eliminate these symptoms. There is a pressing need for objective non-invasive
approaches to measure symptoms and understand disease mechanisms. We developed an
in-depth workflow combining urine metabolomics analysis and machine learning
bioinformatics to characterize metabolic alterations and support objective
diagnosis of LUTS. Machine learning feature selection and statistical tests were
combined to identify candidate biomarkers, which were statistically validated
with leave-one-patient-out cross-validation and absolutely quantified by selected
reaction monitoring assay. Receiver operating characteristic analysis showed
highly-accurate prediction power of candidate biomarkers to stratify patients
into disease or non-diseased categories. The key metabolites and pathways may be
possibly correlated with smooth muscle tone changes, increased collagen content,
and inflammation, which have been identified as potential contributors to urinary
dysfunction in humans and rodents. Periurethral tissue staining revealed a
significant increase in collagen content and tissue stiffness in men with LUTS.
Together, our study provides the first characterization and validation of LUTS
urinary metabolites and pathways to support the future development of a urine
based diagnostic test for LUTS.
PMID- 27502323
TI - A Cost-Effectiveness Analysis of Using the JBR.10-Based 15-Gene Expression
Signature to Guide Adjuvant Chemotherapy in Early Stage Non-Small-Cell Lung
Cancer.
AB - BACKGROUND: Adjuvant chemotherapy (ACT) improved survival in the NCIC Clinical
Trials Group JBR.10 trial of resected stage IB/II non-small-cell lung cancer. A
prognostic 15-gene expression signature was developed, which may also predict for
benefit from ACT. An exploratory economic analysis was conducted to assess the
potential cost-effectiveness of using the 15-gene signature in guiding ACT
decisions. METHODS: A decision analytic model was populated by study patients
with quantitative reverse transcription polymerase chain reaction tumor
profiling, current costs, and quality-adjusted survival. Analysis was performed
over the 6-year follow-up from the perspective of the Canadian public health care
system in 2015 Canadian dollars (discounted 5%/year). Incremental cost
effectiveness and cost-utility ratios were determined for ACT versus observation
using clinical stage, gene signature, or a combined approach to select treatment.
RESULTS: The mean survival gain of ACT versus observation was higher using the
gene signature (1.86 years) compared with clinical stage (1.28 years). Although
more costly, ACT guided by the gene signature remained cost-effective at
$10,421/life-year gained (95% confidence interval [CI], $466-$19,568 Canadian),
comparable to stage-directed selection ($7081/life-year gained; 95% CI, -$2370 to
$14,721; P = .52). Incremental cost-utility ratios were $13,452/quality-adjusted
life-year (95% CI, $373-$31,949) and $9194/quality-adjusted life-year (95% CI,
$4104 to $23,952), respectively (P = .53). Comparing the standard and test-and
treat approaches, use of the gene signature did not significantly alter survival
compared with the standard strategy, but it reduced the ACT rate by 25%.
CONCLUSION: If validated, the use of the 15-gene expression signature to select
patients for ACT may increase the survival gain of treatment in patients with
high-risk stage IB/II non-small-cell lung cancer, while avoiding toxicities in
low-risk patients.
PMID- 27502324
TI - Graphene-mediated microfluidic transport and nebulization via high frequency
Rayleigh wave substrate excitation.
AB - The deposition of a thin graphene film atop a chip scale piezoelectric substrate
on which surface acoustic waves are excited is observed to enhance its
performance for fluid transport and manipulation considerably, which can be
exploited to achieve further efficiency gains in these devices. Such gains can
then enable complete integration and miniaturization for true portability for a
variety of microfluidic applications across drug delivery, biosensing and point
of-care diagnostics, among others, where field-use, point-of-collection or point
of-care functionality is desired. In addition to a first demonstration of
vibration-induced molecular transport in graphene films, we show that the
coupling of the surface acoustic wave gives rise to antisymmetric Lamb waves in
the film which enhance molecular diffusion and hence the flow through the
interstitial layers that make up the film. Above a critical input power, the
strong substrate vibration displacement can also force the molecules out of the
graphene film to form a thin fluid layer, which subsequently destabilizes and
breaks up to form a mist of micron dimension aerosol droplets. We provide
physical insight into this coupling through a simple numerical model, verified
through experiments, and show several-fold improvement in the rate of fluid
transport through the film, and up to 55% enhancement in the rate of fluid
atomization from the film using this simple method.
PMID- 27502325
TI - Investigating the potential role of non-vls genes on linear plasmid 28-1 in
virulence and persistence by Borrelia burgdorferi.
AB - BACKGROUND: The lp28-1 plasmid is required for persistent infection by the Lyme
disease spirochete, Borrelia burgdorferi. Mutational studies on this plasmid have
shown that the vls locus is important for antigenic variation of the VlsE
lipoprotein that leads to immune evasion and persistence. However, it is still
unknown whether the vls system is the only genetic locus on this plasmid
necessary for long-term infection, and thus the potential role of non-vls genes
on lp28-1 in virulence and persistence is yet to be fully determined. Despite
extensive mutational analyses, two lp28-1 regions containing the ORFs bbf19 -
bbf22 and bbf27 - bbf30 have not yet been mutated in their entirety. RESULTS: In
this study, we set out to establish if these unstudied regions of lp28-1 play a
role in spirochete persistence. Results show that the generated mutants were
fully infectious in immunocompetent mice, and were able to persist for 91 days
following infection. Following this finding, ospC expression by these mutants was
determined, as it has been reported that spirochetes lacking lp28-1 fail to
downregulate expression of this lipoprotein leading to immune clearance. Data
presented here failed to show a definitive difference in ospC expression levels
during host infection when the mutants were compared to the wild type.
CONCLUSIONS: Overall, the results strongly suggest that non-vls genes residing on
lp28-1 do not play a role in spirochete persistence during infection of the
mammalian host, and that the regions under study are likely not involved in the
regulation of ospC expression. In conjunction with previous studies involving
mutation of non-vls loci on lp28-1, these findings suggest that the vls locus is
likely the sole genetic element on this plasmid responsible for immune evasion
and persistence exhibited by the Lyme disease pathogen.
PMID- 27502327
TI - Treatment for avascular necrosis of bone in people with sickle cell disease.
AB - BACKGROUND: Avascular necrosis of bone is a frequent and severe complication of
sickle cell disease and its treatment is not standardised. This is an update of a
previously published Cochrane Review. OBJECTIVES: To determine the impact of any
surgical procedure compared with other surgical interventions or non-surgical
procedures, on avascular necrosis of bone in people with sickle cell disease in
terms of efficacy and safety. SEARCH METHODS: We searched the Cochrane Cystic
Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register,
comprising references identified from comprehensive electronic database searches
and handsearches of relevant journals and abstract books of conference
proceedings. Additional trials were sought from the reference lists of papers
identified by the search strategy.Date of the most recent search of the Group's
Haemoglobinopathies Trials Register: 27 May 2016. SELECTION CRITERIA: Randomized
clinical trials comparing specific therapies for avascular necrosis of bone in
people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Each author
independently extracted data and assessed trial quality. Since only one trial was
identified, meta-analysis was not possible. MAIN RESULTS: One trial (46
participants) was eligible for inclusion. After randomization eight participants
were withdrawn, mainly because they declined to participate in the trial. Data
were analysed for 38 participants at the end of the trial. After a mean follow up
of three years, hip core decompression and physical therapy did not show clinical
improvement when compared with physical therapy alone using the score from the
original trial (an improvement of 18.1 points for those treated with intervention
therapy versus an improvement of 15.7 points with control therapy). There was no
significant statistical difference between groups regarding major complications
(hip pain, risk ratio 0.95 (95% confidence interval 0.56 to 1.60; vaso-occlusive
crises, risk ratio 1.14 (95% confidence interval 0.72 to 1.80; very low quality
of evidence); and acute chest syndrome, risk ratio 1.06 (95% confidence interval
0.44 to 2.56; very low quality of evidence)). This trial did not report results
on mortality or quality of life. AUTHORS' CONCLUSIONS: We found no evidence that
adding hip core decompression to physical therapy achieves clinical improvement
in people with sickle cell disease with avascular necrosis of bone compared to
physical therapy alone. However, we highlight that our conclusion is based on one
trial with high attrition rates. Further randomized controlled trials are
necessary to evaluate the role of hip-core depression for this clinical
condition. Endpoints should focus on participants' subjective experience (e.g.
quality of life and pain) as well as more objective 'time-to-event' measures
(e.g. mortality, survival, hip longevity). The availability of participants to
allow adequate trial power will be a key consideration for endpoint choice.
PMID- 27502326
TI - A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy
and Safety of Fimasartan/Amlodipine Combined Therapy Versus Fimasartan
Monotherapy in Patients With Essential Hypertension Unresponsive to Fimasartan
Monotherapy.
AB - PURPOSE: The goal of this study was to evaluate whether the blood pressure
lowering efficacy of fimasartan/amlodipine combination therapy was superior to
that of fimasartan monotherapy after 8 weeks of treatment in patients with
hypertension who had failed to respond adequately to fimasartan monotherapy.
METHODS: This trial was a randomized, double-blind, multicenter, Phase III
clinical study. Patients who failed to respond after 4 weeks of treatment with 60
mg daily of fimasartan (sitting systolic blood pressure [SiSBP]) >=140 mm Hg)
were randomized to receive either daily fimasartan 60 mg or fimasartan/amlodipine
60 mg/10 mg. The primary efficacy end point was the change in SiSBP from baseline
to week 8. Secondary end points included the change in SiSBP from baseline to
week 4, the changes in sitting diastolic blood pressure from baseline to weeks 4
and 8, and the response rate (SiSBP <140 mm Hg or decrease in SiSBP >=20 mm Hg)
or control rate (SiSBP <140 mm Hg) at week 8. Treatment-emergent adverse events
were also assessed. FINDINGS: Of 143 patients randomized to treatment, 137
patients who had available efficacy data were analyzed. The mean age of patients
was 59.1 (8.9) years, and 100 (73.0%) were male. Baseline SiSBP and sitting
diastolic blood pressure were 150.6 (9.2) mm Hg and 91.7 (8.6) mm Hg,
respectively. In the fimasartan/amlodipine combination group, a greater reduction
in SiSBP from baseline to week 8 was observed compared with the fimasartan group
(7.8 [13.3] mm Hg in the fimasartan group vs 20.5 [14.6] mm Hg in the
fimasartan/amlodipine group; P < 0.0001). This reduction was observed after 4
weeks. The mean SiSBP changes from baseline to week 4 were 8.1 (15.8) mm Hg in
the fimasartan group and 20.1 (14.7) mm Hg in the fimasartan/amlodipine group (P
< 0.0001). At week 8, the response rate was significantly higher in the
fimasartan/amlodipine (82.1%) group than in the fimasartan (32.9%) group (P <
0.0001). The control rate at week 8 was also higher in the fimasartan/amlodipine
(79.1%) group than in the fimasartan (31.4%) group (P < 0.0001). Adverse drug
reactions were observed in 9 patients (6.3%), with no significant differences
between treatment groups. There were no serious adverse events associated with
the study drugs. IMPLICATIONS: Fimasartan/amlodipine combination therapy
exhibited superior efficacy in reducing blood pressure, with no increase in
adverse drug reactions, compared with fimasartan monotherapy. ClinicalTrials.gov
identifier: NCT02152306.
PMID- 27502329
TI - Pacing-Induced Cardiomyopathy: "It's Tough to Make Predictions, Especially About
the Future"*.
PMID- 27502328
TI - Metabolic and diffusional limitations of photosynthesis in fluctuating irradiance
in Arabidopsis thaliana.
AB - A better understanding of the metabolic and diffusional limitations of
photosynthesis in fluctuating irradiance can help identify targets for improving
crop yields. We used different genotypes of Arabidopsis thaliana to characterise
the importance of Rubisco activase (Rca), stomatal conductance (gs), non
photochemical quenching of chlorophyll fluorescence (NPQ) and sucrose phosphate
synthase (SPS) on photosynthesis in fluctuating irradiance. Leaf gas exchange and
chlorophyll fluorescence were measured in leaves exposed to stepwise increases
and decreases in irradiance. rwt43, which has a constitutively active Rubisco
enzyme in different irradiance intensities (except in darkness), showed faster
increases than the wildtype, Colombia-0, in photosynthesis rates after step
increases in irradiance. rca-2, having decreased Rca concentration, showed lower
rates of increase. In aba2-1, high gs increased the rate of change after stepwise
irradiance increases, while in C24, low gs tended to decrease it. Differences in
rates of change between Colombia-0 and plants with low levels of NPQ (npq1-2,
npq4-1) or SPS (spsa1) were negligible. In Colombia-0, the regulation of Rubisco
activation and of gs were therefore limiting for photosynthesis in fluctuating
irradiance, while levels of NPQ or SPS were not. This suggests Rca and gs as
targets for improvement of photosynthesis of plants in fluctuating irradiance.
PMID- 27502332
TI - Fundamental literature and hot topics on rural left-behind children in China: a
bibliometric analysis.
AB - BACKGROUND: Recently, the literature on rural left-behind children in China has
rapidly grown. However, no comprehensive review of the status of knowledge on the
issue exists. METHODS: A co-cited network map of 327 studies (covering 1998
through 2014) drawn from the Chinese Social Studies Citation Index database was
analysed. RESULTS: Using visualization software, the results identified three
fundamental studies on the issue and four hot topics: interventions, deviant
behaviours, mental health and family childrearing strategies. The analysis found
that knowledge on this topic could be furthered by (1) focusing on protective
factors and (2) integrating disciplines by standardizing concepts and measures.
CONCLUSIONS: These study's results are an important reference for the development
of theories, practices and policies regarding rural left-behind children in
China.
PMID- 27502333
TI - Two cases of disseminated superficial actinic porokeratosis treated with daylight
mediated photodynamic therapy.
PMID- 27502334
TI - Advances in Controlled Drug Delivery for Treatment of Osteoporosis.
AB - Osteoporosis, which is characterized by resorption of bone exceeding formation,
remains a significant human health concern, and the impact of this condition will
only increase with the "graying" of the worldwide population. This review focuses
on current and emerging approaches for delivering therapeutic agents to restore
bone remodeling homeostasis. Well-known antiresorptive and anabolic agents, such
as estrogen, estrogen analogs, bisphosphonates, calcitonin, and parathyroid
hormone, along with newer modulators and antibodies, are primarily administered
orally, intravenously, or subcutaneously. Although these treatments can be
effective, continuing problems include patient noncompliance and adverse systemic
or remote-site effects. Controlled drug delivery via polymeric, targeted, and
active release systems extends drug half-life by shielding against premature
degradation and improves bioavailability while also providing prolonged,
sustained, or intermittent release at therapeutic doses to more effectively treat
osteoporosis and associated fracture risk.
PMID- 27502336
TI - Pre-NELA vs NELA - has anything changed, or is it just an audit exercise?
AB - BACKGROUND Following evidence suggestive of high mortality following emergency
laparotomies, the National Emergency Laparotomy Audit (NELA) was set up,
highlighting key standards in emergency service provision. Our aim was to compare
our NHS trust's adherence to these recommendations immediately prior to, and
following, the launch of NELA, and to compare patient outcome. METHODS This was a
retrospective study of patients who underwent an emergency laparotomy over the
course of 6 months - 3 months either side of the initiation of NELA. RESULTS
There were 44 patients before the initiation of NELA (pre-NELA, PN group) and 55
in the first 3 months of NELA (N group). We saw a significant increase in the
proportion of patients whose decision to operate was made by the consultant:
75.0% in the PN group vs 100% in N group (subsequent data presented in this
order) (P < 0.001). The presence of a consultant surgeon (75.0% vs 83.6%, P =
0.321) and anaesthetist (100.0% vs 90.9%, P = 0.064) in theatres were comparable
in both groups. Risk stratification based on Portsmouth Physiological and
Operative Severity Score for the enUmeration of Mortality and Morbidity (P
POSSUM) score showed no difference in high-risk patients in both groups (47.7% vs
36.4%, P = 0.306). With the NELA initiative, however, significantly more patients
were admitted directly from theatres to the critical care unit, when compared
with the pre-NELA period (9.1% vs 27.3%, P = 0.038). This also reflected a
significant reduction in unexpected escalation to a higher level of care during
this period (10.0% vs 0%, P = 0.036). Significantly more patients had uneventful
recovery in the NELA period (52.3 vs 76.4%, P = 0.018), although there was no
difference in 30-day mortality between the groups (2.3% vs 7.3%, P = 0.378).
CONCLUSIONS This study demonstrated a greater degree of consultant involvement in
the decision to operate during NELA. More high-risk patients have been identified
preoperatively with diligent risk assessment and, hence, have been proactively
admitted to critical care units following laparotomy, which may account for the
significant reduction in unexpected escalation to level 2 or level 3 care and
thus in overall better patient outcomes.
PMID- 27502335
TI - Does smoking influence the physical activity and lung cancer relation? A
systematic review and meta-analysis.
AB - Research suggests an inverse association between physical activity and lung
cancer. However, whether the relation is modified by degree of smoking adjustment
has not been summarized. We conducted a meta-analysis of physical activity and
lung cancer focusing on evaluating whether smoking status and the degree of
smoking adjustment influenced the association. Comparing high versus low physical
activity levels from 25 observational studies yielded a lung cancer summary
relative risk (RR) of 0.79 [95 % confidence interval (CI) = 0.72-0.87], with RRs
of 0.87 (95 % CI = 0.80-0.94) for cohort studies and 0.57 (95 % CI = 0.46-0.71)
for case-control studies. In further analyses restricted to cohort studies,
physical activity was inversely related to lung cancer among former smokers (RR =
0.68, 95 % CI = 0.51-0.90) and current smokers (RR = 0.80, 95 % CI = 0.70-0.90),
whereas the association was null among never smokers (RR = 1.05, 95 % CI = 0.78
1.40, p interaction = 0.26). The degree of smoking adjustment did not modify the
association (p interaction = 0.73). Physical activity was unrelated to lung
cancer among never smokers but it was inversely associated with lung cancer among
former and current smokers. Although the physical activity and lung cancer
relation was not modified by smoking status or degree of smoking adjustment,
residual confounding by smoking remains a possible explanation for the relations
observed.
PMID- 27502337
TI - Prediction of histological stage based on cystoscopic appearances of newly
diagnosed bladder tumours.
AB - INTRODUCTION In the 75-80% of urothelial bladder cancers (UBC) presenting as non
muscle invasive bladder cancer (NMIBC), transurethral resection of bladder tumour
(TURBT) is the key treatment and staging procedure. In the 20-25% of patients
with muscle invasive bladder cancer (MIBC), further cross-sectional imaging is
required to complete the staging process before considering radical treatment.
Given the adverse effects of ionising radiation, clinicians identify patients
believed to have MIBC, and so requiring further imaging pre-TURBT, at the tumour
histology/stage based on the tumour's visual characteristics. There is minimal
evidence describing the accuracy of such predictions in newly-diagnosed patients.
METHODS Over a 6-year period, a database of patients undergoing resection of
newly-diagnosed bladder lesions in a single UK centre was prospectively
established. Predictions based on histology were simultaneously recorded, and the
accuracy of these predictions of histology/stage subsequently assessed. RESULTS
One hundred and twenty two (73.1%) patients with histologically confirmed NMIBC
had predictions recorded versus 45 (26.9%) patients with MIBC. Visual assessment
predictions of MIBC had a sensitivity of 88.9% (95% confidence interval [CI]
76.5%-95.2%) and a specificity of 91.0% (95% CI 84.6%-94.9%), giving a positive
predictive value of 78.4% (95% CI 65.4%-87.5%) and a negative predictive value of
95.7% (95% CI 90.3%-98.1%). CONCLUSIONS We find that visual assessment is
accurate in predicting the presence of MIBC. This supports the practice of
stratifying patients at the time of initial cystoscopy for those requiring
further radiological staging pre-TURBT.
PMID- 27502338
TI - The right colic artery: An anatomical demonstration and its relevance in the
laparoscopic era.
AB - INTRODUCTION Hemicolectomies are not tailored in right-sided colon cancer
resections, despite significant variation in the incidence and origin of the
right colic artery (RCA). Early evidence suggests that removal of the relevant
lymphovascular package and associated cancer as part of complete mesocolic
excision (CME), rather than the entire right colon, may produce better outcomes.
Advancing laparoscopic techniques are making this possible, and so it is
increasingly important to more precisely define the anatomy of the RCA. METHODS
To demonstrate the incidence and variation of the RCA, 25 formalin embalmed
cadavers were dissected. Consent to dissection and photography was obtained under
Human Tissue Act regulations. RESULTS Eleven female and 14 male cadavers (mean
age 79.7 years, range 41-95 years) were included. The RCA originated from the
right branch of the middle colic artery in nine cadavers (36%), while it arose
from the superior mesenteric artery in eight cases (32%) and from the ileocolic
or root of the middle colic artery in a smaller number of specimens. The RCA was
absent in two individuals. CONCLUSIONS The RCA arises from the right branch of
the middle colic artery in a considerable number of cases. The literature to date
does not reflect the precision of anatomical understanding required for CME;
hence, a new definition for the right colic vessel is proposed.
PMID- 27502339
TI - The evolution of intraoperative conversion in video assisted thoracoscopic
lobectomy.
AB - INTRODUCTION Unplanned conversion to thoracotomy remains a major concern in video
assisted thoracoscopic surgery (VATS) lobectomy. This study aimed to investigate
the development of a VATS lobectomy programme over a five-year period, with a
focus on the causes and consequences of unplanned conversions. METHODS A single
centre retrospective review was performed of patients who underwent complete
anatomical lung resection initiated by VATS between January 2010 and April 2015.
RESULTS In total, 1,270 patients underwent a lobectomy in the study period and
684 (53.9%) of these were commenced thoracoscopically. There were 75 cases
(10.9%) with unplanned conversion. The proportion of lobectomies started as VATS
was significantly higher in the second half of the study period (2010-2012:
277/713 [38.8%], 2013-2015: 407/557 [73.1%], p<0.001). The conversion rate
dropped initially from 20.4% (11/54) in 2010 to 9.9% (15/151) in 2013 and then
remained consistently under 10% until 2015. Conversions were most commonly
secondary to vascular injury (26/75, 34.7%). Patients undergoing unplanned
conversion had a longer length of stay than VATS completed patients (9 vs 6 days,
p<0.001). There was a higher incidence of respiratory failure (10/75 [14.1%] vs
23/607 [3.8%], p<0.001) and 30-day mortality (7/75 [9.3%] vs 6/607 [1.0%],
p=0.003) in patients with unplanned conversion than in those with completed VATS.
CONCLUSIONS As our VATS lobectomy programme developed, the unplanned conversion
rate dropped initially and then remained constant at approximately 10%. With
increasing unit experience, it is both safe and technically possible to complete
the majority of lobectomy procedures thoracoscopically.
PMID- 27502340
TI - Abdominal fat ratio - a novel parameter for predicting conversion in laparoscopic
colorectal surgery.
AB - INTRODUCTION Laparoscopic surgery has become the standard for colorectal cancer
resection in the UK but it can be technically challenging in patients who are
obese. Patients whose body fat is mainly inside the abdominal cavity are more
challenging than those whose fat is mainly outside the abdominal cavity.
Abdominal fat ratio (AFR) is a simple parameter proposed by the authors to aid
identification of this subgroup. MATERIALS AND METHODS All 195 patients who
underwent elective, laparoscopic colorectal cancer resections from March 2010 to
November 2013 were included in the study. For patients who were obese (body mass
index greater than 30), preoperative staging computed tomography was used to
determine AFR. This was assessed by two different, blinded observers and compared
with conversion rate. RESULTS Of the 195 patients, 58 (29.7%) fell into the obese
group and 137 (70.3%) into the non-obese group. The median AFR of the obese group
that were converted to open surgery was significantly higher at 5.9 compared with
those completed laparoscopically (3.3, P = 0.0001, Mann-Whitney). There was no
significant difference in conversion rate when looking at body mass index, tumour
site or size. DISCUSSION Previous studies have found body mass index, age,
gender, previous abdominal surgery, site and locally advanced tumours to be
associated with an increased risk of conversion. This study adds AFR to the list
of risk factors. CONCLUSION AFR is a simple, reproducible parameter which can
help to predict conversion risk in obese patients undergoing colorectal cancer
resection.
PMID- 27502341
TI - An unusual diaphragmatic hernia with gastric perforation and sub-acute
presentation.
AB - Gastric perforation into the thoracic cavity through a diaphragmatic hernia is
rare but, when it occurs, patients present in severe distress, with mortality
approaching 50%. We present a unique case in which a fibrotic reaction between
the stomach and the parietal pleura led to a subacute presentation upon
perforation. The extra time that this afforded led to more effective
multidisciplinary team management and ultimately an excellent outcome for the
patient.
PMID- 27502342
TI - Non-steroidal anti-inflammatory drug-induced diaphragm disease: an uncommon cause
of small bowel obstruction.
AB - Surgeons frequently deal with small bowel obstruction. However, small bowel
obstruction caused by non-steroidal anti-inflammatory drug (NSAID)-induced
diaphragm disease is very rare. The diagnosis is challenging, as symptoms are
often non-specific and radiological studies remain inconclusive. We present a
case of a 63-year-old man who, after an extensive diagnostic work-up and small
bowel resection for obstructive symptoms, was finally diagnosed with NSAID
induced diaphragm disease as confirmed by histology. An unusual aspect of this
case is that the patient stopped using NSAIDs after he was diagnosed with a
gastric ulcer 2-years previously. This suggests that NSAID-induced diaphragms of
the small bowel take some time to develop and underlines the importance of
careful history taking.
PMID- 27502343
TI - Giant cell aortitis in treatment-naive human immunodeficiency virus and hepatitis
C coinfection.
AB - Giant cell arteritis is a common form of vasculitis, although involvement of the
aorta is unusual. There is no established association between giant cell aortitis
and human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection.
We present the case of a 46-year-old female coinfected with HIV and HCV who had
never received antiretroviral therapy and developed symptoms of deteriorating
shortness of breath on exertion. Investigations demonstrated aortic root and
ascending aorta dilatation, along with severe aortic valve regurgitation, for
which the patient underwent valve-sparing aortic root replacement (a David
procedure). Histopathology confirmed giant cell aortitis.
PMID- 27502344
TI - Management of joint dislocations of the lower limb in Larsen syndrome: practical
approach.
AB - INTRODUCTION Larsen syndrome is an autosomal-dominant osteochondrodysplasia
characterised by large joint dislocations and craniofacial anomalies. CASE
HISTORY We present a rare case of Larsen syndrome with bilateral dislocated hips
and knees and severe clubfeet at 7-year follow-up. We undertook bilateral open
reduction of both hips at age 8 months. This procedure was preceded by open
reduction and left-knee V-Y quadricepsplasty at age 4 months following a failed
trial of closed reduction of the left knee. Both feet had a severe deformity
(Pirani score of 5.5 and 6.0) and were treated using the Ponseti method, but the
left foot relapsed at 24 months and required posteromedial release. CONCLUSIONS
We tried to address the difficult questions on the timing and sequence of
surgical interventions by treating clubfeet and dislocated knees early using
Ponseti casts which included the knees. Open reduction of hips was done later,
and further interventions were guided by functional needs.
PMID- 27502345
TI - Supra-aural gossypiboma: case report of a retained textile surgical sponge in an
unusual location.
AB - Gossypiboma or retained surgical sponge is an infrequently encountered surgical
complication, more so in the head and neck region. A literature search did not
reveal a previously reported case of retained or concealed surgical sponge after
microscopic ear surgery. We present a unique and previously unreported case of a
25-year-old male who presented with a cystic swelling in the right supra-aural
region 5 months post-modified radical mastoidectomy of the right ear. Surgical
excision of the swelling revealed a retained surgical sponge. We emphasise the
importance of counting surgical sponges after every surgical step to minimise the
incidence of such retained surgical items.
PMID- 27502346
TI - Peritoneal encapsulation; a rare cause of bowel obstruction.
AB - Peritoneal encapsulation is a rare congenital cause of bowel obstruction in
children. We present the case of a 12-year-old male with severe dehydration and
recurrent episodes of vomiting. This pathology should be considered in cases of
bowel obstruction with a virgin abdomen.
PMID- 27502347
TI - A rare case of primary epithelioid angiosarcoma of the ureter.
AB - Angiosarcoma is an extremely rare vascular malignancy with a 1-year survival rate
of 50%, regardless of tumour origin. Distant metastases are common and occur in
the lungs, bone, lymph nodes and soft tissues. The majority of patients with
angiosarcoma present with localised disease, although 25-45% have distant
metastases at presentation. There are few reported cases of angiosarcomas of the
bladder and we report the second case in the literature of primary angiosarcoma
of the ureter. We suggest that, in atypical manifestations of suspected
urothelial malignancy, the multidisciplinary team considers the possibility of
rarer, aggressive tumours early. This may influence clinical decision making
towards offering radical treatments earlier, before it is too late to do so owing
to aggressive oncological behaviour.
PMID- 27502348
TI - Sexual Orientation Self-Presentation Among Bisexual-Identified Women and Men:
Patterns and Predictors.
AB - Writing on the experiences of bisexual-identified people has highlighted the
potential complexity of the ongoing process of deciding when and how to present
one's sexual orientation identity to others (Rust, 2002). The two studies
presented here were designed to contribute basic knowledge regarding self
presentation of sexual orientation among bisexual people. In Study 1, bisexual
participants (N = 147) were less likely than their lesbian and gay (LG) peers (N
= 191) to present their actual orientation to others, and more likely to present
themselves as having a sexual orientation different from their actual
orientation. These sexual orientation differences were explained by gender of
romantic partner and uncertainty about one's sexual orientation. Sexual
orientation differences also emerged in links between self-presentation and
outness level. For example, bisexual participants who presented themselves as LG
had relatively high everyday outness levels; in contrast, LG participants who
presented themselves as bisexual had relatively low everyday outness levels. In
Study 2, 240 bisexual women and men indicated their levels of outness as a sexual
minority person (potentially including identification as gay, lesbian, queer) and
specifically as bisexual. Outness was higher with respect to status as a sexual
minority compared to status as bisexual; the magnitude of this difference was
predicted by gender of romantic partner and uncertainty about one's sexual
orientation. Moreover, even controlling for outness as a sexual minority person,
well-being was predicted by outness as bisexual to family members.
PMID- 27502349
TI - Moving Transgender Care Forward within Public Health Organizations: Inclusion of
Facial Feminizing Surgery in the Swedish National Treatment Recommendations.
PMID- 27502350
TI - Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis.
AB - The Female Sexual Function Index (FSFI) is a psychometrically sound and popular
19-item self-report measure, but its length may preclude its use in studies with
multiple outcome measures, especially when sexual function is not a primary
endpoint. Only one attempt has been made to create a shorter scale, resulting in
the Italian FSFI-6, later translated into Spanish and Korean without further
psychometric analysis. Our study evaluated whether a subset of items on the 19
item English-language FSFI would perform as well as the full-length FSFI in peri-
and postmenopausal women. We used baseline data from 898 peri- and postmenopausal
women recruited from multiple communities, ages 42-62 years, and enrolled in
randomized controlled trials for vasomotor symptom management. Goals were to (1)
create a psychometrically sound, shorter version of the FSFI for use in peri- and
postmenopausal women as a continuous measure and (2) compare it to the Italian
FSFI-6. Results indicated that a 9-item scale provided more information than the
FSFI-6 across a spectrum of sexual functioning, was able to capture sample
variability, and showed sufficient range without floor or ceiling effects. All
but one of the items from the Italian 6-item version were included in the 9-item
version. Most omitted FSFI items focused on frequency of events or experiences.
When assessment of sexual function is a secondary endpoint and subject burden
related to questionnaire length is a priority, the 9-item FSFI may provide
important information about sexual function in English-speaking peri- and
postmenopausal women.
PMID- 27502351
TI - Views and Experiences of Malaysian Family Medicine Trainees of Female Sexual
Dysfunction.
AB - Sociocultural factors have been shown to be important influencers of sexual
health and sexuality. Hence, the aim of our study was to explore the views and
experiences of family medicine trainees regarding female sexual dysfunction (FSD)
with a focus on the barriers and facilitators towards the initiation of
conversation on this topic. A qualitative study design involving semi-structured
focus group discussions (FGDs) was conducted with 19 family medicine trainees in
Malaysia. The conceptual framework used was based on the Theory of Planned
Behavior. Thematic approach was used to analyze the data. Participants perceived
FSD as being uncommon and unimportant. According to our participants, patients
often presented with indirect complaints, and doctors were not proactive in
asking about FSD. Three main barriers were identified: doctor factors, perceived
patient factors, and system factors. Lack of confidence, knowledge, experience,
time, and embarrassment were the key barriers identified at the doctors' level.
Lack of awareness, among patients regarding FSD, and local cultural and religious
norms were the perceived patient barriers. System barriers were lack of time and
privacy. Various facilitators, such as continuous medical education and public
forums, were suggested as means to encourage family medicine trainees to initiate
discussion on sexual matters during consultations. In conclusion, family medicine
trainees found it difficult to initiate conversation on FSD with patients.
Interventions to encourage conversation on FSD should target this and other
identified barriers.
PMID- 27502353
TI - Electroclinical phenotypes and outcomes in TBC1D24-related epilepsy.
AB - TBC1D24 is a newly recognized gene in which variations lead to variable clinical
phenotypes including drug-resistant epilepsy. We report four patients with novel
variants of TBC1D24 demonstrating drug-resistant focal epilepsy, developmental
delays, and head growth deceleration. All patients had seizure semiologies
consisting of prolonged, unilateral, focal clonic activity of the arm, leg or
face, in addition to generalized clonic or myoclonic seizures. Ictal EEG
characteristics included epilepsia partialis continua, epilepsy of infancy with
migrating focal seizures, and other focal seizures with indiscrete interictal
ictal transitions. Two seemingly unrelated Navajo patients with identical
variations experienced super-refractory status epilepticus at 9 months of age,
with one achieving resolution with ketogenic diet therapy. Our series suggests
that TBC1D24-related epilepsy can manifest with hypotonia, developmental delays,
and a variety of focal-onset seizures prone to electroclinical dissociation.
PMID- 27502354
TI - Electron ionization mass spectrometric fragmentation and multiple reaction
monitoring quantification of trimethylsilyl derivatives of cucurbic acid and its
6,7-stereoisomers.
AB - RATIONALE: Isomeric cucurbic acids derive from the reduction of the keto group of
jasmonic acids. These growth regulators are natural constituents of various
higher plants and fungi. Elucidation of electron ionization mass spectrometry
(EIMS) fragmentation pathways of the trimethylsilyl (TMS) derivatives of the
different stereoisomers is essential for their characterization and
quantification in natural samples. METHODS: EIMS fragmentation pathways of TMS
derivatives of isomeric cucurbic acids and methyl cucurbates were investigated.
These pathways were deduced by: (i) low-energy collision-induced dissociation
(CID) gas chromatography/tandem mass spectrometry (GC/MS/MS), (ii) accurate mass
measurement, and (iii) deuterium labelling. RESULTS: CID-MS/MS analyses, accurate
mass measurement and deuterium labelling allowed us to elucidate EIMS
fragmentations of TMS derivatives of several isomeric cucurbic acids and methyl
cucurbates and to propose some specific fragment ions useful in addition to
chromatographic retention times to characterize individual stereoisomers. As an
application of some of the described fragmentations, isomeric cucurbic acids were
characterized and quantified in multiple reaction monitoring (MRM) mode in
different natural samples. CONCLUSIONS: The EIMS fragmentations of TMS
derivatives of isomeric cucurbic acids appear to be distinct when the ether and
ester groups are in the cis or trans positions, allowing for an easy
differentiation of individual stereoisomers in natural samples. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27502355
TI - The effect of experimental osteoporosis on bone regeneration: Part 1, histology
findings.
AB - OBJECTIVES: To histologically define the healing events occurring in calvarial
critical size defects (CSDs) following treatment with a collagen barrier for
guided bone regeneration (GBR) and a particulate graft in healthy and
osteoporotic conditions. MATERIAL AND METHODS: Thirty-six 10-month-old, female,
Wistar rats were used in this study. Half of them were ovariectomized (OVX) and
fed with a low-calcium diet to induce an osteoporotic-like status. In each animal
of both groups, two 5-mm CSDs were created, one in the centre of each parietal
bone, and they were treated with a deproteinized bovine bone mineral (DBBM)
particulate graft and a bi-layer collagen membrane. Six OVX and six healthy
control rats were randomly euthanized at 7, 14 and 30 days. One defect per animal
was randomly processed for decalcified histology. Three central sections were
used for qualitative histology and histomorphometric analysis. RESULTS: No
significant difference in terms of percentage of newly formed bone was detected
between the two groups at the different healing periods. However, a trend towards
less bone formation and of poorer quality, expressed as reduced bone maturation,
was detected in the OVX animals at 30 days. DISCUSSION: According to this study,
GBR with a collagen barrier and a DBBM graft can be successfully obtained also in
osteoporotic-like conditions. Future studies considering longer healing periods
and controlling for the confounding factors arising from the use of a particulate
graft are needed to confirm these data.
PMID- 27502356
TI - Dynamically Tuning the Up-conversion Luminescence of Er(3+)/Yb(3+) Co-doped
Sodium Niobate Nano-crystals through Magnetic Field.
AB - In this work, we show here that the up-conversion luminescence of
NaNbO3:Er(3+)/Yb(3+) nano-materials can be modulated by magnetic field and a
enhancement of up-conversion intensities by a factor of about 2 for
Er(3+):(4)S3/2 -> (4)I15/2 obtained at 30 T and about 5.4 for Er(3+):(4)F9/2 ->
(4)I15/2 obtained at 20 T. The increased up-conversion luminescence are mainly
interpreted in terms of the enhanced non-radiation transition from (4)I11/2 to
(4)I13/2 of Er(3+) ions and the spin-orbital coupling (that is "mixing" effect)
in crystal field by an external magnetic field. Meanwhile, we observed
continuously spectra broadening with growing the magnetic field intensity, which
is ascribed to the "mixing" effect induced by magnetic field and the difference
of g factor of sub-bands. This bi-functional material with controllable optical
magnetic interactions has various potential applications, such as optical
detection of magnetic field, etc.
PMID- 27502358
TI - Analytical relationships for prediction of the mechanical properties of
additively manufactured porous biomaterials.
AB - Recent developments in additive manufacturing techniques have motivated an
increasing number of researchers to study regular porous biomaterials that are
based on repeating unit cells. The physical and mechanical properties of such
porous biomaterials have therefore received increasing attention during recent
years. One of the areas that have revived is analytical study of the mechanical
behavior of regular porous biomaterials with the aim of deriving analytical
relationships that could predict the relative density and mechanical properties
of porous biomaterials, given the design and dimensions of their repeating unit
cells. In this article, we review the analytical relationships that have been
presented in the literature for predicting the relative density, elastic modulus,
Poisson's ratio, yield stress, and buckling limit of regular porous structures
based on various types of unit cells. The reviewed analytical relationships are
used to compare the mechanical properties of porous biomaterials based on
different types of unit cells. The major areas where the analytical relationships
have improved during the recent years are discussed and suggestions are made for
future research directions. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res
Part A: 104A: 3164-3174, 2016.
PMID- 27502360
TI - Immunotherapy: Here or there, PD-L1 can be anywhere.
PMID- 27502361
TI - Driving factors of dinoflagellate cyst distribution in surface sediments of a
Mediterranean lagoon with limited access to the sea.
AB - Seasonal distribution of dinoflagellate cysts were studied at five surface
sediment study stations in Ghar El Melh Lagoon (GML) (Tunisia) in relation to
physicochemical parameters and phytoplankton abundance in the water column. At
least sixteen dinocyst types were identified, dominated mainly by Protoperidinium
spp., Scrippsiella trochoidea complex, Lingulodinum machaerophorum, Alexandrium
spp. and Gymnodinium spp., along with many round brown cysts. Cyst abundance
ranged from 0 to 229g-1 dry sediment. No significant differences in cyst
distribution were found among stations, though a significant variation was
observed among seasons with cyst dominance in autumn. No significant variation
was found between cyst abundance and the different abiotic factors monitored,
neither in the water column (physicochemical parameters) nor in the sediment (%
H2O). Low dinocyst abundance was consistent with the dominance of non-cyst
forming dinoflagellates in the GML water column.
PMID- 27502362
TI - Fundao Dam collapse: Oceanic dispersion of River Doce after the greatest
Brazilian environmental accident.
AB - On 5 November 2015, the Fundao tailings dam collapsed and its content first
reached River Doce and then the Atlantic Ocean by 22 November. This study focuses
on the oceanic time and space patterns of river discharge dispersion. By using an
ocean model together with nLw(555) and RGB images from MODIS sensors, the river
plume was followed for 2months after the arrival of the tailings at the ocean.
The results show the huge effect of this accident and reveal that riverine waters
may have dispersed hundreds of kilometres, reaching regions as far as the shelf
in front of the city of Rio de Janeiro. The movement of the freshwater was
essentially to the south in accordance with the seasonal wind regime. Episodic
frontal systems, leading to wind reversion, and oceanic mesoscale features
contribute to the offshore dispersion of the plume. The region more often in
contact with the riverine waters was located at the inner shelf between the river
mouth and the city of Vitoria, turning to the outer shelf and shelf break at
lower latitudes.
PMID- 27502363
TI - Culture supernatants of cervical cancer cells induce an M2 phenotypic profile in
THP-1 macrophages.
AB - Patients with cervical cancer (CxCa) typically present an infiltrate of tumor
associated macrophages, which is associated with a poor prognosis. We found that
CxCa cell lines (HeLa, SiHa, and C-33A) secreted factors involved in regulating
tumor growth including IL-6, IL-4, PDGFAA, HGF, VEGF, ANG-2, and TGF-beta3. We
assessed the effects of culture supernatants from these cell lines on macrophages
derived from the THP-1 cell line. Macrophages treated with culture supernatants
from CxCa cells developed an M2-like phenotype with expression of CD163, low
nitric oxide release, and high secretion of IL-6, PDGFAA, HGF, ANG-2, and VEGF.
The macrophages continued to produce PDGFAA, PDGFBB, and VEGF 48h after the CxCa
cell culture supernatants were removed. The induction of M2 macrophages in vivo
favors tumor growth, angiogenesis, tissue remodeling, and metastasis. These
results demonstrated that factors secreted by CxCa cells induced a stable M2
phenotype in THP-1 macrophages.
PMID- 27502359
TI - Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?
AB - The prevalence of obesity, of type 2 diabetes mellitus (T2DM), and of cancer are
all increasing globally. The relationships between these diseases are complex,
and thus difficult to elucidate; nevertheless, evidence supports the hypothesis
that obesity increases the risks of both T2DM and certain cancers. Further
complexity arises from controversial evidence that specific drugs used in the
treatment of T2DM increase or decrease cancer risk or influence cancer prognosis.
Herein, we review the current evidence from studies that have addressed these
relationships, and summarize the methodological challenges that are frequently
encountered in such research. We also outline the physiology that links obesity,
T2DM, and neoplasia. Finally, we outline the practical principles relevant to the
increasingly common challenge of managing patients who have been diagnosed with
both diabetes and cancer.
PMID- 27502364
TI - Phosphatidylcholine as a metabolic cue for determining B cell fate and function.
AB - In activated B cells, increased production of phosphatidylcholine (PtdCho), the
most abundant cellular phospholipid, is handled primarily by the CDP-choline
pathway. B cell-specific deletion of CTP:phosphocholine cytidylyltransferase
alpha (CCTalpha), the rate-limiting enzyme in the CDP-choline pathway, led to
augmented IgM secretion and reduced IgG production, suggesting that PtdCho
synthesis is required for germinal center reactions. To specifically assess
whether PtdCho influences B cell fate during germinal center responses, we
examined immune responses in mice whereby PtdCho synthesis is disrupted in B
cells that have undergone class switch recombination to IgG1 (referred to as
either Cgamma1wt/wt, Cgamma1Cre/wt or Cgamma1Cre/Cre based on Cre copy number).
Serum IgG1 was markedly reduced in naive Cgamma1Cre/wt and Cgamma1Cre/Cre mice,
while levels of IgM and other IgG subclasses were similar between Cgamma1Cre/wt
and Cgamma1wt/wt control mice. Serum IgG2b titers were notably reduced and IgG3
titers were increased in Cgamma1Cre/Cre mice compared with controls. Following
immunization with T cell-dependent antigen NP-KLH, control mice generated high
titer IgG anti-NP while IgG anti-NP titers were markedly reduced in both
immunized Cgamma1Cre/wt and Cgamma1Cre/Cre mice. Correspondingly, the frequency
of NP-specific IgG antibody-secreting cells was also reduced in spleens and bone
marrow of Cgamma1Cre/wt and Cgamma. 1Cre/Cre mice compared to control mice.
Interestingly, though antigen-specific IgM B cells were comparable between
Cgamma1Cre/wt, Cgamma1Cre/Cre and control mice, the frequency and number of IgG1
NP-specific B cells was reduced only in Cgamma1Cre/Cre mice. These data indicate
that PtdCho is required for the generation of both germinal center-derived B
cells and antibody-secreting cells. Further, the reduction in class-switched ASC
but not B cells in Cgamma1Cre/wt mice suggests that ASC have a greater demand for
PtdCho compared to germinal center B cells.
PMID- 27502365
TI - Whipple's arthritis.
AB - Whipple's disease is a chronic systemic infection that is due to the bacterial
agent Tropheryma whipplei and can be cured by appropriate antibiotic therapy. The
typical patient is a middle-aged man. Rheumatologists are in a prime position to
handle Whipple's disease. The classical presentation combines weight loss and
diarrhea, preceded in three-quarters of patients by a distinctive pattern of
joint manifestations that run an intermittent course, at least initially. The
mean time from joint symptom onset to the diagnosis of Whipple's disease is 6
years. Either oligoarthritis or chronic polyarthritis with negative tests for
rheumatoid factors (RFs) develops. If the diagnosis is missed, progression to
chronic septic destructive polyarthritis may occur. Spondyloarthritis has also
been reported, as well as a few cases of diskitis or, even more rarely, of
hypertrophic osteoarthropathy. In most patients with the classical form of
Whipple's disease, periodic acid-Schiff (PAS) staining of duodenal and jejunal
biopsies shows macrophagic inclusions that contain bacteria. However, the
involvement of the bowel may be undetectable clinically or, less often,
histologically, and even PCR testing of bowel biopsies may be negative.
Therefore, when nothing points to bowel disease, rheumatologists should consider
T. whipplei infection in middle-aged men with unexplained intermittent
oligoarthritis. PCR testing allows the detection of T. whipplei genetic material
in joint fluid, saliva, and feces. This test is now a first-line diagnostic
investigation, although T. whipplei is a rare cause of unexplained RF-negative
oligoarthritis or polyarthritis in males. PCR testing can provide an early
diagnosis before the development of severe systemic complications, which are
still fatal in some cases.
PMID- 27502366
TI - Individual and structural environmental influences on utilization of iron and
folic acid supplementation among pregnant women in Harare, Zimbabwe.
AB - Micronutrient deficiencies are prevalent among Zimbabweans with serious health
and social implications. Due to a lack of a national micronutrient food
fortification policy, the Zimbabwe Ministry of Health and Child Care established
a policy for the prevention of maternal micronutrient deficiencies, which centres
on pregnant women receiving daily iron and folic acid (IFA) at their first
antenatal care visit and throughout pregnancy. Despite these efforts, utilization
of IFA supplementation in pregnancy in Zimbabwe is low. This study aimed to
understand the experiences and knowledge of IFA supplementation among pregnant
women and healthcare workers in Harare, Zimbabwe, and the influence of health
service and social environments on utilization. Semi-structured in-depth
interviews were conducted in Shona and English, with pregnant women (n = 24) and
healthcare workers (n = 14) providing direct antenatal care services to pregnant
women in two high-density community clinics. Data were analysed thematically
using NVivo 10. Influences on utilization were at the individual and structural
environmental levels. Reasons for low utilization of IFA supplementation included
forgetting to take IFA, side effects, misconceptions about IFA, limited access to
nutrition information, delayed entry or non-uptake of antenatal care and social
norms of pregnant women for IFA supplementation. Utilization was enhanced by
knowledge of risks and benefits of supplementation, fear of negative health
complications with non-utilization, family support and healthcare worker
recommendation for supplementation. Study findings can inform approaches to
strengthen micronutrient supplementation utilization to improve the micronutrient
status of pregnant women to decrease maternal mortality and improve overall
maternal and child health in Zimbabwe. (c) 2016 John Wiley & Sons Ltd.
PMID- 27502367
TI - Interval Appendectomy: Finding the Breaking Point for Cost-Effectiveness.
AB - BACKGROUND: Patients with phlegmonous appendicitis can be managed nonoperatively,
yet debate continues about the need for interval appendectomy (IA), given the low
risk of recurrence or neoplasm. We sought to determine for which patient age
interval appendectomy is cost-effective. METHODS: Using TreeAge software, a cost
effectiveness model was developed. Two strategies were compared, IA and no
interval appendectomy (NIA). Interval appendectomy patients were modeled with
probability of benign pathology, cancer or inflammatory bowel disease, and
possible operative complications. Patients with NIA were modeled with the
probability of recurrence. The probability of malignancy or inflammatory bowel
disease developing, or death occurring during a lifetime, was modeled. Base case
scenarios at 18, 35, and 50 years old were completed using a Monte Carlo
microsimulation. Probabilistic sensitivity analysis was completed using 2
dimensional sample as a Monte Carlo microsimulation to account for variability
for patients 18 to 60 years old. Probabilities of complications developing,
pathologic diagnosis requiring additional management, and state utility were
extracted from published data. Costs were collected from the Centers for Medicare
and Medicaid Services and utility was quality-adjusted life years (QALY).
RESULTS: For an 18-year-old patient, IA costs $9,417.22 with a gain of 16.59
QALYs compared with NIA, which costs $11,613.57 with a gain of 16.52 QALYs. For a
35-year-old, IA costs $8,989.16 with 9.1 QALYs gained. No interval appendectomy
costs $6,614.61 and 9.09 QALYs gained. For the 35-year-old patient, the interval
cost-effectiveness ratio comparing NIA with IA is $237,455/QALY. As patient age
increases, the interval cost-effectiveness ratio increases. Using a willingness
to-pay threshold of $50,000/QALY, IA remains cost-effective until the patient is
33 years old. CONCLUSIONS: Interval appendectomy should be considered in patients
younger than 34 years of age.
PMID- 27502368
TI - Physician-Owned Surgical Hospitals Outperform Other Hospitals in Medicare Value
Based Purchasing Program.
AB - BACKGROUND: The Hospital Value-Based Purchasing Program measures value of care
provided by participating Medicare hospitals and creates financial incentives for
quality improvement and fosters increased transparency. Limited information is
available comparing hospital performance across health care business models.
STUDY DESIGN: The 2015 Hospital Value-Based Purchasing Program results were used
to examine hospital performance by business model. General linear modeling
assessed differences in mean total performance score, hospital case mix index,
and differences after adjustment for differences in hospital case mix index.
RESULTS: Of 3,089 hospitals with total performance scores, categories of
representative health care business models included 104 physician-owned surgical
hospitals, 111 University HealthSystem Consortium, 14 US News & World Report
Honor Roll hospitals, 33 Kaiser Permanente, and 124 Pioneer accountable care
organization affiliated hospitals. Estimated mean total performance scores for
physician-owned surgical hospitals (64.4; 95% CI, 61.83-66.38) and Kaiser
Permanente (60.79; 95% CI, 56.56-65.03) were significantly higher compared with
all remaining hospitals, and University HealthSystem Consortium members (36.8;
95% CI, 34.51-39.17) performed below the mean (p < 0.0001). Significant
differences in mean hospital case mix index included physician-owned surgical
hospitals (mean 2.32; p < 0.0001), US News & World Report honorees (mean 2.24; p
= 0.0140), and University HealthSystem Consortium members (mean 1.99; p <
0.0001), and Kaiser Permanente hospitals had lower case mix value (mean 1.54; p <
0.0001). Re-estimation of total performance scores did not change the original
results after adjustment for differences in hospital case mix index. CONCLUSIONS:
The Hospital Value-Based Purchasing Program revealed superior hospital
performance associated with business model. Closer inspection of high-value
hospitals can guide value improvement and policy-making decisions for all
Medicare Value-Based Purchasing Program Hospitals.
PMID- 27502370
TI - Prostaglandin E2 Reduces Cardiac Contractility via EP3 Receptor.
AB - BACKGROUND: Prostaglandin E2 (PGE2) EP receptors EP3 and EP4 signal via decreased
and increased cAMP production, respectively. Previously, we reported that
cardiomyocyte-specific EP4 knockout mice develop dilated cardiomyopathy with
reduced ejection fraction. Thus, we hypothesized that PGE2 increases
contractility via EP4 but decreases contractility via EP3. METHODS AND RESULTS:
The effects of PGE2 and the EP1/EP3 agonist sulprostone on contractility were
examined in the mouse Langendorff preparation and in adult mouse cardiomyocytes.
Isolated hearts of adult male C57Bl/6 mice were perfused with PGE2 (10(-6) M) or
sulprostone (10(-6) M) and compared with vehicle. Both PGE2 and sulprostone
decreased +dp/dt (P<0.01) and left ventricular developed pressure (P<0.001) with
reversal by an EP3 antagonist. In contrast, the EP4 agonist had the opposite
effect. Adult mouse cardiomyocytes contractility was also reduced after treatment
with either PGE2 or sulprostone for 10 minutes. We then examined the acute
effects of PGE2, sulprostone, and the EP4 agonist on expression of phosphorylated
phospholamban and sarcoendoplasmic reticulum Ca(2+)-ATPase 2a in adult mouse
cardiomyocytes using Western blot. Treatment with either PGE2 or sulprostone
decreased expression of phosphorylated phospholamban corrected to total
phospholamban, whereas treatment with the EP4 agonist had the opposite effect.
Sarcoendoplasmic reticulum Ca(2+)-ATPase 2a expression was unaffected. Finally,
we examined the effect of these compounds in vivo using pressure-volume loops.
Both PGE2 and sulprostone decreased +dp/dt, whereas the EP4 agonist increased
+dp/dt. CONCLUSIONS: Contractility is reduced via the EP3 receptor but increased
via EP4. These effects may be mediated through changes in phospholamban
phosphorylation and has relevance to detrimental effects of inflammation.
PMID- 27502369
TI - Postnatal Loss of Kindlin-2 Leads to Progressive Heart Failure.
AB - BACKGROUND: The striated muscle costamere, a multiprotein complex at the boundary
between the sarcomere and the sarcolemma, plays an integral role in maintaining
striated muscle structure and function. Multiple costamere-associated proteins,
such as integrins and integrin-interacting proteins, have been identified and
shown to play an increasingly important role in the pathogenesis of human
cardiomyopathy. Kindlin-2 is an adaptor protein that binds to the integrin beta
cytoplasmic tail to promote integrin activation. Genetic deficiency of Kindlin-2
results in embryonic lethality, and knockdown of the Kindlin-2 homolog in
Caenorhabditis elegans and Danio rerio suggests that it has an essential role in
integrin function and normal muscle structure and function. The precise role of
Kindlin-2 in the mammalian cardiac myocyte remains to be determined. METHODS AND
RESULTS: The current studies were designed to investigate the role of Kindlin-2
in the mammalian heart. We generated a series of cardiac myocyte-specific Kindlin
2 knockout mice with excision of the Kindlin-2 gene in either developing or adult
cardiac myocytes. We found that mice lacking Kindlin-2 in the early developing
heart are embryonic lethal. We demonstrate that deletion of Kindlin-2 at late
gestation or in adult cardiac myocytes resulted in heart failure and premature
death, which were associated with enlargement of the heart and extensive
fibrosis. In addition, integrin beta1D protein expression was significantly
downregulated in the adult heart. CONCLUSIONS: Kindlin-2 is required to maintain
integrin beta1D protein stability. Postnatal loss of Kindlin-2 from cardiac
myocytes leads to progressive heart failure, showing the importance of costameric
proteins like Kindlin-2 for homeostasis of normal heart function.
PMID- 27502371
TI - Savannahs of Asia: antiquity, biogeography, and an uncertain future.
AB - The savannahs of Asia remain locally unrecognized as distinctive ecosystems, and
continue to be viewed as degraded forests or seasonally dry tropical forests.
These colonial-era legacies are problematic, because they fail to recognize the
unique diversity of Asian savannahs and the critical roles of fire and herbivory
in maintaining ecosystem health and diversity. In this review, we show that: the
palaeo-historical evidence suggests that the savannahs of Asia have existed for
at least 1 million years, long before widespread landscape modification by
humans; savannah regions across Asia have levels of C4 grass endemism and
diversity that are consistent with area-based expectations for non-Asian
savannahs; there are at least three distinct Asian savannah communities, namely
deciduous broadleaf savannahs, deciduous fine-leafed and spiny savannahs and
evergreen pine savannahs, with distinct functional ecologies consistent with fire
and herbivory-driven community assembly. Via an analysis of savannah climate
domains on other continents, we map the potential extent of savannahs across
Asia. We find that the climates of African savannahs provide the closest
analogues for those of Asian deciduous savannahs, but that Asian pine savannahs
occur in climates different to any of the savannahs in the southern continents.
Finally, we review major threats to the persistence of savannahs in Asia,
including the mismanagement of fire and herbivory, alien woody encroachment,
afforestation policies and future climate uncertainty associated with the
changing Asian monsoon. Research agendas that target these issues are urgently
needed to manage and conserve these ecosystems.This article is part of the themed
issue 'Tropical grassy biomes: linking ecology, human use and conservation'.
PMID- 27502372
TI - Clarifying the confusion: old-growth savannahs and tropical ecosystem
degradation.
AB - Ancient tropical grassy biomes are often misrecognized as severely degraded
forests. I trace this confusion to several factors, with roots in the nineteenth
century, including misinterpretations of the nature of fire in savannahs,
attempts to reconcile savannah ecology with Clementsian succession, use of
physiognomic (structural) definitions of savannah and development of tropical
degradation frameworks focused solely on forests. Towards clarity, I present two
models that conceptualize the drivers of ecosystem degradation as operating in
both savannahs and forests. These models highlight how human-induced
environmental changes create ecosystems with superficially similar physiognomies
but radically different conservation values. Given the limitation of physiognomy
to differentiate savannahs from severely degraded forests, I present an
alternative approach based on floristic composition. Data from eastern lowland
Bolivia show that old-growth savannahs can be reliably distinguished by eight
grass species and that species identity influences ecosystem flammability. I
recommend that scientists incorporate savannahs in tropical degradation
frameworks alongside forests, and that savannah be qualified as old-growth
savannah in reference to ancient grassy biomes or derived savannah in reference
to deforestation. These conceptual advances will require attention not only to
tree cover, but also to savannah herbaceous plant species and their
ecologies.This article is part of the themed issue 'Tropical grassy biomes:
linking ecology, human use and conservation'.
PMID- 27502373
TI - Many shades of green: the dynamic tropical forest-savannah transition zones.
AB - The forest-savannah transition is the most widespread ecotone in tropical areas,
separating two of the most productive terrestrial ecosystems. Here, we review
current understanding of the factors that shape this transition, and how it may
change under various drivers of local or global change. At broadest scales, the
location of the transition is shaped by water availability, mediated strongly at
local scales by fire regimes, herbivory pressure and spatial variation in soil
properties. The frequently dynamic nature of this transition suggests that forest
and savannah can exist as alternative stable states, maintained and separated by
fire-grass feedbacks and tree shade-fire suppression feedback. However, this
theory is still contested and the relative contributions of the main biotic and
abiotic drivers and their interactions are yet not fully understood. These
drivers interplay with a wide range of ecological processes and attributes at the
global, continental, regional and local scales. The evolutionary history of the
biotic and abiotic drivers and processes plays an important role in the current
distributions of these transitions as well as in their species composition and
ecosystem functioning. This ecotone can be sensitive to shifts in climate and
other driving factors, but is also potentially stabilized by negative feedback
processes. There is abundant evidence that these transitions are shifting under
contemporary global and local changes, but the direction of shift varies
according to region. However, it still remains uncertain how these transitions
will respond to rapid and multi-faceted ongoing current changes, and how
increasing human influence will interact with these shifts.This article is part
of the themed issue 'Tropical grassy biomes: linking ecology, human use and
conservation'.
PMID- 27502374
TI - Competing consumers: contrasting the patterns and impacts of fire and mammalian
herbivory in Africa.
AB - Fire and herbivory are the two consumers of above-ground biomass globally. They
have contrasting impacts as they differ in terms of selectivity and temporal
occurrence. Here, we integrate continental-scale data on fire and herbivory in
Africa to explore (i) how environmental drivers constrain these two consumers and
(ii) the degree to which each consumer affects the other. Environments conducive
to mammalian herbivory are not necessarily the same as those conducive to fire,
although their spheres of influence do overlap-especially in grassy ecosystems
which are known for their frequent fires and abundance of large mammalian
herbivores. Interactions between fire and herbivory can be competitive,
facultative or antagonistic, and we explore this with reference to the potential
for alternative ecosystem states. Although fire removes orders of magnitude more
biomass than herbivory their methane emissions are very similar, and in the past,
herbivores probably emitted more methane than fire. We contrast the type of
herbivory and fire in different ecosystems to define 'consumer-realms'.This
article is part of the themed issue 'Tropical grassy biomes: linking ecology,
human use and conservation'.
PMID- 27502375
TI - Reforestation or conservation? The attributes of old growth grasslands in South
Africa.
AB - Deforestation as a result of burning and land conversion in the tropics and
subtropics has been widely studied and active restoration of forests has been
widely promoted. Besides other benefits, reforestation can sequester carbon
thereby reducing CO2 emissions to the atmosphere. However, before grasslands are
targeted for 'reforestation', it is necessary to distinguish whether they are
ancient natural grasslands or secondary vegetation colonizing deforested areas.
Here we report the results of a study comparing primary grasslands in South
Africa with 4-40 year old secondary grasslands recovering from afforestation with
Pinus species. Primary grasslands had significantly higher plant species richness
overall, especially of forb species. Ground cover of primary grasslands was more
evenly distributed among species than secondary grasslands which tended to mono
dominance. Forbs with underground storage organs (USOs) were common in primary
grasslands but conspicuously absent in the recovering systems. Comparison of
secondary grasslands of different ages (up to 40 years) showed negligible
recovery of the original species composition. Three key features distinguish old
growth primary from secondary grasslands: total and forb species numbers,
evenness of species contributions to cover and the presence of USOs. Old growth
grasslands also differed in their fire response, showing significant post-burn
resprouting and fire-stimulated flowering in contrast to secondary grasslands.
Though similar contrasting attributes of ancient and secondary grasslands have
been reported in South America, more studies are needed to explore their
generality in other geographical regions.This article is part of the themed issue
'Tropical grassy biomes: linking ecology, human use and conservation'.
PMID- 27502376
TI - The future distribution of the savannah biome: model-based and biogeographic
contingency.
AB - The extent of the savannah biome is expected to be profoundly altered by climatic
change and increasing atmospheric CO2 concentrations. Contrasting projections are
given when using different modelling approaches to estimate future distributions.
Furthermore, biogeographic variation within savannahs in plant function and
structure is expected to lead to divergent responses to global change. Hence the
use of a single model with a single savannah tree type will likely lead to biased
projections. Here we compare and contrast projections of South American, African
and Australian savannah distributions from the physiologically based Thornley
transport resistance statistical distribution model (TTR-SDM)-and three versions
of a dynamic vegetation model (DVM) designed and parametrized separately for
specific continents. We show that attempting to extrapolate any continent
specific model globally biases projections. By 2070, all DVMs generally project a
decrease in the extent of savannahs at their boundary with forests, whereas the
TTR-SDM projects a decrease in savannahs at their boundary with aridlands and
grasslands. This difference is driven by forest and woodland expansion in
response to rising atmospheric CO2 concentrations in DVMs, unaccounted for by the
TTR-SDM. We suggest that the most suitable models of the savannah biome for
future development are individual-based dynamic vegetation models designed for
specific biogeographic regions.This article is part of the themed issue 'Tropical
grassy biomes: linking ecology, human use and conservation'.
PMID- 27502377
TI - Ecosystem services from southern African woodlands and their future under global
change.
AB - Miombo and mopane woodlands are the dominant land cover in southern Africa.
Ecosystem services from these woodlands support the livelihoods of 100 M rural
people and 50 M urban dwellers, and others beyond the region. Provisioning
services contribute $9 +/- 2 billion yr(-1) to rural livelihoods; 76% of energy
used in the region is derived from woodlands; and traded woodfuels have an annual
value of $780 M. Woodlands support much of the region's agriculture through
transfers of nutrients to fields and shifting cultivation. Woodlands store 18-24
PgC carbon, and harbour a unique and diverse flora and fauna that provides
spiritual succour and attracts tourists. Longstanding processes that will impact
service provision are the expansion of croplands (0.1 M km(2); 2000-2014),
harvesting of woodfuels (93 M tonnes yr(-1)) and changing access arrangements.
Novel, exogenous changes include large-scale land acquisitions (0.07 M km(2);
2000-2015), climate change and rising CO2 The net ecological response to these
changes is poorly constrained, as they act in different directions, and
differentially on trees and grasses, leading to uncertainty in future service
provision. Land-use change and socio-political dynamics are likely to be dominant
forces of change in the short term, but important land-use dynamics remain
unquantified.This article is part of the themed issue 'Tropical grassy biomes:
linking ecology, human use and conservation'.
PMID- 27502378
TI - Woody encroachment and its consequences on hydrological processes in the
savannah.
AB - Woody encroachment due to changes in climate or in the disturbance regimes (fire
and herbivory) has been observed throughout the savannah biome over the last
century with ecological, hydrological and socioeconomic consequences. We assessed
changes in tree density and basal area and estimated changes in rain interception
by the canopies across a 5-year period over a biomass gradient in Cerrado
vegetation protected from fire. We modelled throughfall, stemflow and net
rainfall on the basis of tree basal area (TBA). Tree density increased by an
average annual rate of 6.7%, basal area at 5.7% and rain interception by the
canopies at 0.6% of the gross rainfall. Independent of the vegetation structure,
we found a robust relationship of 0.9% less rainfall reaching the ground as TBA
increases by 1 m(2) ha(-1) Increases in tree biomass with woody encroachment may
potentially result in less water available for uptake by plants and to recharge
rivers and groundwater reserves. Given that water is a seasonally scarce resource
in all savannahs, woody encroachment may threaten the ecosystem services related
to water resources.This article is part of the themed issue 'Tropical grassy
biomes: linking ecology, human use and conservation'.
PMID- 27502380
TI - Charcoal production in the Mopane woodlands of Mozambique: what are the trade
offs with other ecosystem services?
AB - African woodlands form a major part of the tropical grassy biome and support the
livelihoods of millions of rural and urban people. Charcoal production in
particular is a major economic activity, but its impact on other ecosystem
services is little studied. To address this, our study collected biophysical and
social datasets, which were combined in ecological production functions, to
assess ecosystem service provision and its change under different charcoal
production scenarios in Gaza Province, southern Mozambique. We found that
villages with longer histories of charcoal production had experienced declines in
wood suitable for charcoal, firewood and construction, and tended to have lower
perceived availabilities of these services. Scenarios of future charcoal impacts
indicated that firewood and woody construction services were likely to trade-off
with charcoal production. However, even under the most extreme charcoal scenario,
these services were not completely lost. Other provisioning services, such as
wild food, medicinal plants and grass, were largely unaffected by charcoal
production. To reduce the future impacts of charcoal production, producers must
avoid increased intensification of charcoal extraction by avoiding the expansion
of species and sizes of trees used for charcoal production. This is a major
challenge to land managers and policymakers in the area.This article is part of
the themed issue 'Tropical grassy biomes: linking ecology, human use and
conservation'.
PMID- 27502379
TI - The spatial distribution of African savannah herbivores: species associations and
habitat occupancy in a landscape context.
AB - Herbivores play an important role in determining the structure and function of
tropical savannahs. Here, we (i) outline a framework for how interactions among
large mammalian herbivores, carnivores and environmental variation influence
herbivore habitat occupancy in tropical savannahs. We then (ii) use a Bayesian
hierarchical model to analyse camera trap data to quantify spatial patterns of
habitat occupancy for lions and eight common ungulates of varying body size
across an approximately 1100 km(2) landscape in the Serengeti ecosystem. Our
results reveal strong positive associations among herbivores at the scale of the
entire landscape. Lions were positively associated with migratory ungulates but
negatively associated with residents. Herbivore habitat occupancy differed with
body size and migratory strategy: large-bodied migrants, at less risk of
predation and able to tolerate lower quality food, were associated with high
NDVI, while smaller residents, constrained to higher quality forage, avoided
these areas. Small herbivores were strongly associated with fires, likely due to
the subsequent high-quality regrowth, while larger herbivores avoided burned
areas. Body mass was strongly related to herbivore habitat use, with larger
species more strongly associated with riverine and woodlands than smaller
species. Large-bodied migrants displayed diffuse habitat occupancy, whereas
smaller species demonstrated fine-scale occupancy reflecting use of smaller
patches of high-quality habitat. Our results demonstrate the emergence of strong
positive spatial associations among a diverse group of savannah herbivores, while
highlighting species-specific habitat selection strongly determined by herbivore
body size.This article is part of the themed issue 'Tropical grassy biomes:
linking ecology, human use and conservation'.
PMID- 27502381
TI - Reconciling agriculture, carbon and biodiversity in a savannah transformation
frontier.
AB - Rapidly rising populations and likely increases in incomes in sub-Saharan Africa
make tens of millions of hectares of cropland expansion nearly inevitable, even
with large increases in crop yields. Much of that expansion is likely to occur in
higher rainfall savannas, with substantial costs to biodiversity and carbon
storage. Zambia presents an acute example of this challenge, with an expected
tripling of population by 2050, good potential to expand maize and soya bean
production, and large areas of relatively undisturbed miombo woodland and
associated habitat types of high biodiversity value. Here, we present a new model
designed to explore the potential for targeting agricultural expansion in ways
that achieve quantitatively optimal trade-offs between competing economic and
environmental objectives: total converted land area (the reciprocal of potential
yield); carbon loss, biodiversity loss and transportation costs. To allow
different interests to find potential compromises, users can apply varying
weights to examine the effects of their subjective preferences on the spatial
allocation of new cropland and its costs. We find that small compromises from the
objective to convert the highest yielding areas permit large savings in
transportation costs, and the carbon and biodiversity impacts resulting from
savannah conversion. For example, transferring just 30% of weight from a yield
maximizing objective equally between carbon and biodiversity protection
objectives would increase total cropland area by just 2.7%, but result in avoided
costs of 27-47% for carbon, biodiversity and transportation. Compromise solutions
tend to focus agricultural expansion along existing transportation corridors and
in already disturbed areas. Used appropriately, this type of model could help
countries find agricultural expansion alternatives and related infrastructure and
land use policies that help achieve production targets while helping to conserve
Africa's rapidly transforming savannahs.This article is part of the themed issue
'Tropical grassy biomes: linking ecology, human use and conservation'.
PMID- 27502382
TI - The underestimated biodiversity of tropical grassy biomes.
AB - For decades, there has been enormous scientific interest in tropical savannahs
and grasslands, fuelled by the recognition that they are a dynamic and
potentially unstable biome, requiring periodic disturbance for their maintenance.
However, that scientific interest has not translated into widespread appreciation
of, and concern about threats to, their biodiversity. In terms of biodiversity,
grassy biomes are considered poor cousins of the other dominant biome of the
tropics-forests. Simple notions of grassy biomes being species-poor cannot be
supported; for some key taxa, such as vascular plants, this may be valid, but for
others it is not. Here, we use an analysis of existing data to demonstrate that
high-rainfall tropical grassy biomes (TGBs) have vertebrate species richness
comparable with that of forests, despite having lower plant diversity. The
Neotropics stand out in terms of both overall vertebrate species richness and
number of range-restricted vertebrate species in TGBs. Given high rates of land
cover conversion in Neotropical grassy biomes, they should be a high priority for
conservation and greater inclusion in protected areas. Fire needs to be actively
maintained in these systems, and in many cases re-introduced after decades of
inappropriate fire exclusion. The relative intactness of TGBs in Africa and
Australia make them the least vulnerable to biodiversity loss in the immediate
future. We argue that, like forests, TGBs should be recognized as a critical-but
increasingly threatened-store of global biodiversity.This article is part of the
themed issue 'Tropical grassy biomes: linking ecology, human use and
conservation'.
PMID- 27502383
TI - Understanding patterns of land-cover change in the Brazilian Cerrado from 2000 to
2015.
AB - Clearing tropical vegetation impacts biodiversity, the provision of ecosystem
services, and thus ultimately human welfare. We quantified changes in land cover
from 2000 to 2015 across the Cerrado biome of northern Minas Gerais state,
Brazil. We assessed the potential biophysical and socio-economic drivers of the
loss of Cerrado, natural regeneration and net cover change at the municipality
level. Further, we evaluated correlations between these land change variables and
indicators of human welfare. We detected extensive land-cover changes in the
study area, with the conversion of 23 446 km(2) and the natural regeneration of
13 926 km(2), resulting in a net loss of 9520 km(2) The annual net loss (-1.2%
per year) of the cover of Cerrado is higher than that reported for the whole
biome in similar periods. We argue that environmental and economic variables
interact to underpin rates of conversion of Cerrado, most severely affecting more
humid Cerrado lowlands. While rates of Cerrado regeneration are important for
conservation strategies of the remaining biome, their integrity must be
investigated given the likelihood of encroachment. Given the high frequency of
land abandonment in tropical regions, secondary vegetation is fundamental to
maintain biodiversity and ecosystem services. Finally, the impacts of Cerrado
conversion on human welfare likely vary from local to regional scales, making it
difficult to elaborate land-use policies based solely on socio-economic
indicators.This article is part of the themed issue 'Tropical grassy biomes:
linking ecology, human use and conservation'.
PMID- 27502384
TI - Woody encroachment over 70 years in South African savannahs: overgrazing, global
change or extinction aftershock?
AB - Woody encroachment in 'open' biomes like grasslands and savannahs is occurring
globally. Both local and global drivers, including elevated CO2, have been
implicated in these increases. The relative importance of different processes is
unresolved as there are few multi-site, multi-land-use evaluations of woody plant
encroachment. We measured 70 years of woody cover changes over a 1020 km(2) area
covering four land uses (commercial ranching, conservation with elephants,
conservation without elephants and communal rangelands) across a rainfall
gradient in South African savannahs. Different directions of woody cover change
would be expected for each different land use, unless a global factor is causing
the increases. Woody cover change was measured between 1940 and 2010 using the
aerial photo record. Detection of woody cover from each aerial photograph was
automated using eCognitions' Object-based image analysis (OBIA). Woody cover
doubled in all land uses across the rainfall gradient, except in conservation
areas with elephants in low-rainfall savannahs. Woody cover in 2010 in low
rainfall savannahs frequently exceeded the maximum woody cover threshold
predicted for African savannahs. The results indicate that a global factor, of
which elevated CO2 is the likely candidate, may be driving encroachment.
Elephants in low-rainfall savannahs prevent encroachment and localized megafaunal
extinction is a probable additional cause of encroachment.This article is part of
the themed issue 'Tropical grassy biomes: linking ecology, human use and
conservation'.
PMID- 27502386
TI - Correction to 'The zinc sensing receptor, ZnR/GPR39, triggers metabotropic
calcium signalling in colonocytes and regulates occludin recovery in experimental
colitis'.
PMID- 27502385
TI - Tropical grassy biomes: linking ecology, human use and conservation.
AB - Tropical grassy biomes (TGBs) are changing rapidly the world over through a
coalescence of high rates of land-use change, global change and altered
disturbance regimes that maintain the ecosystem structure and function of these
biomes. Our theme issue brings together the latest research examining the
characterization, complex ecology, drivers of change, and human use and ecosystem
services of TGBs. Recent advances in ecology and evolution have facilitated a new
perspective on these biomes. However, there continues to be controversies over
their classification and state dynamics that demonstrate critical data and
knowledge gaps in our quantitative understanding of these geographically
dispersed regions. We highlight an urgent need to improve ecological
understanding in order to effectively predict the sensitivity and resilience of
TGBs under future scenarios of global change. With human reliance on TGBs
increasing and their propensity for change, ecological and evolutionary
understanding of these biomes is central to the dual goals of sustaining their
ecological integrity and the diverse services these landscapes provide to
millions of people.This article is part of the themed issue 'Tropical grassy
biomes: linking ecology, human use and conservation'.
PMID- 27502388
TI - Synthesis and Applications of Nanoflowers.
AB - BACKGROUND: Recent advances in nanotechnology make novel shapes of nanostructured
materials with novel physicochemical properties. Different kinds of materials
including carbon, metals, alloys, metal oxides, conducting polymers, metal
chalcogenides, pnictides and fluorides have been synthesized with small size of
<100 nm with shapes resembled to the natural flowers. The objective of this
review is to provide a broad overview of the synthesis strategies, effects of
different parameters on the morphology of nanoflowers, and their applications.
METHODS: A comprehensive search to assess the current evidence for the synthesis
routs of nanoflowers and applications was conducted. 487 studies became selected
and the quality of papers were appraised and categorized according to type of
nanomaterials. Within each section, the nanomaterials addressed specifically. In
addition, recent patents were reviewed in a separate section. RESULTS: The
nanoflowers exhibited unique properties which were utilized in the design of
efficient applications. These nanostructures can be processed with different
methods. The configuration of flower-like nanostructures can be controlled by
altering experimental parameters, such as the precursor's ratio, temperature and
reaction time. Despite the huge efforts to control and understand the growth
mechanism of these nanostructures, some fundamental phenomena are still not well
understood. Investigation of the fundamental effects of size and morphology on
their properties is required in order to better apply these nanostructured
materials. CONCLUSION: The nanoflowers with interesting properties can be used in
the design of future devices with various applications. The existence of
different routes to synthesis nanoflowers and their unique properties confirm the
importance promoted awareness of potential benefits of nanoflowers in different
applications. The reviewed patents emphasized the importance of these
nanostructures. Therefore, research efforts based on nanoflowers are dynamic and
applicable in various fields.
PMID- 27502387
TI - Bi-insular cortical involvement in anti-NMDA-receptor encephalitis - a case
report.
AB - BACKGROUND: Anti-NMDA-receptor encephalitis is an immune-mediated inflammatory
disorder of the central nervous system. Brain MRI is unremarkable in at least 50%
of patients and highly variable in the remaining patients with signal
abnormalities in different brain regions. Only scarce reports exist on other
imaging modalities. CASE PRESENTATION: A 31-year-old woman sub-acutely developed
psychosis, behavioural changes, amnesia, alternating states of agitation and
mutism, fever and epileptic seizures. Clinically suspected diagnosis of anti-NMDA
receptor encephalitis was confirmed by the detection of anti-NMDA receptor
antibodies in CSF and serum. During the acute phase, brain MRI abnormalities were
found in both insular cortices and hippocampi, whereas F(18)-FDG-PET showed
hypermetabolism bilaterally in insular and prefrontal cortex. After resection of
the underlying ovarian teratoma and with multimodal immunotherapy the patient
substantially improved reaching a modified Rankin Scale score of 2 after 3
months. At follow-up, both hippocampi were still affected on MRI, whereas insular
cortex appeared normal; however, both regions showed prominent glucose
hypometabolism. CONCLUSIONS: Here, we report bi-insular cortical abnormalities on
MRI and F(18)-FDG-PET in a patient with anti-NMDA-receptor encephalitis during
the acute phase and after clinical improvement.
PMID- 27502389
TI - Lymphatic Delivery of Anti-HIV Drug Nanoparticles.
AB - BACKGROUND: HIV infection persists for a longer time in AIDS patient compared to
many other viral diseases. This is mainly because the HIV resides maximally in
lymphatic system mainly the lymph nodes. Most of the present anti-HIV drugs have
very poor bioavailability at lymphatic tissue. Hence, pharmaceutical scientists
have made many efforts to formulate anti-HIV drugs for targeting lymphatic
system. The exploration of nanoparticulate drug delivery systems have been
popularly investigated for lymphatic targeting and for improving therapeutic
efficacy. METHODS: An electronic search was undertaken to review the recent
publications and patents from the available resources on nanoformulations of anti
HIV drugs for lymphatic delivery. RESULTS: Various carrier systems such as
liposomes, polymeric nanoparticles, solid-lipid nanoparticles, nanostructured
lipid carriers, polymeric micelles, dendrimers, and nanocrystals have been tried
for lymphatic targeting. These nanoparticles are widely studied as passive
targeting carriers for lymphatic systems. There is dearth of active targeting for
anti-HIV drugs. The studies on surface modified nanoparticles have shown
promising results for lymphatic targeting. CONCLUSION: One of the reasons for low
success rate in targeting the lymphatic tissue is poor-understanding of
pharmacokinetic interactions of novel delivery systems in disease pathology.
Apart from this, there are several hurdles in biological screening models and
clinical trials. These issues should never be neglected in developing newer
targeted delivery systems for treatment of AIDS.
PMID- 27502390
TI - Nanocarriers as Tools in Delivering Active Compounds for Immune System Related
Pathologies.
AB - BACKGROUND: Immune system related pathologies affect an increasing number of
patients every year, having potentially lethal consequences and requiring
expensive and difficult tolerated treatments. This area of pathologies offers an
excellent potential for the development of innovative solutions such as
nanoformulations; this review aims to describe the main categories of
nanostructured drug delivery platforms that have been developed in order to
achieve a more effective, low toxic treatment in autoimmune pathologies. METHODS:
We conducted a systematic search of peer-reviewed original studies focusing on
nanoformulations suitable for use against autoimmune disorders. Each study was
evaluated by at least two reviewers who applied inclusion and exclusion criteria
in order to establish the quality of the research reported in the selected
papers. The systematic screening of the literature also identified the most
recent patents issued in the field of inflammatory/autoimmune diseases which were
included in the current paper. RESULTS: One hundred ninety-seven bibliographic
titles were included in the review of which fifty-three recently published
patents. Twenty-one papers were selected to define the interaction between
nanoformulations and the immune system triggering either immunosuppression or
immunostimulation. Thirty-seven papers outlined the characteristics of liposomal
formulations that have been reported as treatment for several autoimmune diseases
including multiple sclerosis. Twentythree articles provided data on the main
lipid nanoparticles of the first and second generation which may include
physiological lipids with low cytotoxicity. Gold nanoparticles were described by
thirteen papers which highlighted the advantages of the new hybrid organic
inorganic nanoparticles vs. the classical ionic gold compounds. Polymeric
nanoformulations were the subject of fifty-nine papers that described their
preparation as well as various advantages in the treatment of inflammatory
disorders; dendrimers and polymeric micelles were included in the study. Thirty
three studies were selected to outline the benefits provided by the use of
cyclodextrins as carriers for active drugs. The review also identified the
possibility of producing combined nanoformulations (e.g. polymer/cyclodextrin,
liposome/polymer) thus achieving superior therapeutic results. CONCLUSION:
Nanoformulations offer multiple advantages over the classical pharmaceutical
formulations, the main ones being the precise targeted therapy with small doses
of active drugs, longer circulating time in the bloodstream, and high loading
capacity for diagnostic and therapeutic molecules; moreover, the nanoparticles
may be functionalized in order to act as nanotheranostics within the larger frame
of personalized medicine.
PMID- 27502391
TI - The Advanced Aluminum Nitride Synthesis Methods and Its Applications: Patent
Review.
AB - BACKGROUND: High purity nanosized aluminum nitride synthesis is a current issue
for both industry and science. However, there is no up-to-date review considering
the major issues and the technical solutions for different methods. This review
aims to investigate the advanced methods of aluminum nitride synthesis and its
development tendencies. Also the aluminum nitride application patents and
prospects for development of the branch have been considered. METHODS: The patent
search on "aluminum nitride synthesis" has been carried out. The research
activity has been analyzed. Special attention has been paid to the patenting
geography and the leading researchers in aluminum nitride synthesis. RESULTS:
Aluminum nitride synthesis methods have been divided into 6 main groups, the most
studied approaches are carbothermal reduction (88 patents) and direct nitridation
(107 patents). The current issues for each group have been analyzed; the main
trends are purification of the final product and nanopowder synthesis. The
leading researchers in aluminum nitride synthesis have represented 5 countries,
namely: Japan, China, Russia, South Korea and USA. The main aluminum nitride
application spheres are electronics (59,1 percent of applications) and new
materials manufacturing (30,9 percent). CONCLUSION: The review deals with the
state of the art data in nanosized aluminum nitride synthesis, the major issues
and the technical solutions for different synthesis methods. It gives a full
understanding of the development tendencies and of the current leaders in the
sphere.
PMID- 27502392
TI - Effect of Gold/Amine Nanoparticles on Polyaniline Electrochemical Sensitivity to
Formaldehyde.
AB - BACKGROUND: Nanoparticles have a promising potential in electrochemical
sensitivity. Polyaniline (PANI) received significant attention in the latest
years owing to its high conductivity and excellent electrochemical stability.
This research aims to study the effect of gold nanoparticles capped octadecyl
amine (Au/ODA) on polyaniline emeraldine salt (ES) electrochemical sensitivity to
formaldehyde (FA) using DPV technique. Furthermore, ES and Au-ODA/ES have been
applied for the first time in sensing FA. Few relevant patents to the topic have
been reviewed and cited in this article. METHODS: Emeraldine salt (ES) was
prepared by doping the prepared emeraldine base (EB) powder with dodecylbenzene
sulfonic acid (DBSA) at a ratio of 1:2 W/W. Then ES-DBSA was dissolved in
chloroform solution and added to Au/ODA nanoparticles solution to obtain Au/ES
DBSA nanocomposite. FA sensors were prepared by depositing a film from ESDBSA or
Au/ES-DBSA on a working electrode and the potential was measured at FA different
concentrations in Electrochemical cell kit. RESULTS: FTIR and XRD confirmed the
structure of ES-DBSA and Au/ES-DBSA. The obtained results reveal that the ESDBSA
nanosensor is an efficient sensor because it can recognize the low levels of FA
starting from 0.06 ppm. The recorded electrochemical oxidation current shows a
linear direct relationship between the produced current and FA concentration in
case of ES-DBSA nanoparticles while it illustrates a fluctuating signal with
lower sensitivity in the case of the novel prepared nanocomposites (Au/ES-DBSA).
This may be due to the gold capping agent (ODA), which in turn could inhibit the
role of DBSA and decrease the conductivity of the nanocomposite. CONCLUSION:
Herein we described the application of ES-DBSA and Au/ES-DBSA nanocomposite for
the first time as a novel, facile, and cheap method for electrochemical sensitive
detection of formaldehyde. The gold capping agent ODA hinders the ES-DBSA
conductivity through interaction with the DBSA sulfo group.
PMID- 27502393
TI - Effective Strategies for Achieving Scope of Practice Reform in Pennsylvania.
AB - BACKGROUND: Current regulatory impediments prohibit advanced practice registered
nurses from practicing to their full capacity. PURPOSE: To examine the process of
successful removal of scope of practice barriers in Pennsylvania under the Rx4PA
legislation introduced in 2007. METHOD: We used qualitative research techniques,
including purposeful sampling of participants. Twelve stakeholder informed
interviews were conducted between October 2013 and May 2014. Participants were
closely involved with the development of the Rx4PA legislation. Thematic content
analysis was performed to analyze our interviews. DISCUSSION: Interviews
identified overarching themes, including the importance of leveraging years of
grass roots advocacy, identifying political allies, and recognizing mutually
beneficial compromises. CONCLUSIONS: The combination of timing, careful political
maneuvering, and compromise were key to scope of practice reform in Pennsylvania
and may be useful strategies for other states seeking similar practice changes.
PMID- 27502394
TI - Vaccination of rabbits with immunodominant antigens from Sarcoptes scabiei
induced high levels of humoral responses and pro-inflammatory cytokines but
confers limited protection.
AB - BACKGROUND: Vaccination is an attractive ecological alternative to the use of
acaricides for parasite control. However, effective anti-parasite vaccines
against sarcoptic mange have not yet been developed. The purpose of this study
was first to identify Sarcoptes scabiei immunodominant antigens and second to
evaluate them as vaccine candidates in a rabbit/S. scabiei var. cuniculi model.
METHODS: The S. scabiei Sslambda15 immunodominant antigen was selected by
immunoscreening of a S. scabiei var. hominis cDNA. The full-length cDNA was
sequenced and cloned into the pGEX vector and the recombinant protein expressed
in BL21 (DE3) cells and purified. A vaccination trial was performed consisting of
a test group (n = 8) immunised with recAgs (a mix of two recombinant antigens,
Sslambda15 and the previously described Sslambda20?B3) and a control group (n =
8) immunised with PBS. All analyses were performed with R Statistical Environment
with alpha set at 0.050. RESULTS: The full-length open reading frame of the 1,821
nt cloned cDNA encodes a 64 kDa polypeptide, the sequence of which had 96 %
identity with a hypothetical protein of S. scabiei. Sslambda15 was localised by
immunostaining of skin sections in the tegument surrounding the mouthparts and
the coxa in the legs of mites. Rabbit immunisation with recAgs induced high
levels of specific IgG (P < 0.010) and increased levels of total IgEs. However,
no significant clinical protection against S. scabiei challenge was detected.
Unexpectedly, the group immunised with the recAgs mix had significantly higher
lesion scores (P = 0.050) although lower mean mite densities than those observed
in the control group. These results might indicate that the lesions in the recAgs
group were due not only to the mites density but also to an exacerbated
immunological response after challenge, which is in agreement with the specific
high levels of pro-inflammatory cytokines (IL-1 and TNFalpha) detected after
challenge in this group. CONCLUSIONS: The selected antigens delivered as
recombinant proteins had no clinical protective efficacy against S. scabiei
infestation although immunisation reduced mite density. However, these results
pave the way for future studies on alternative production systems, adjuvants,
delivery methods and combinations of antigens in order to manage stimulation of
clinical protective immune responses.
PMID- 27502395
TI - Correlation between invasion mode and the histologic risk assessment model in
oral squamous cell carcinoma.
AB - PURPOSE: The histologic risk assessment (HRA) model was proposed to assess
clinical outcome of oral squamous cell carcinomas (SCCs), and its prognostic
value has been confirmed in several studies, but its underlying molecular
mechanisms has not been fully investigated. The objective of this study was to
evaluate the association between immunohistochemical invasion mode of head and
neck SCC and the HRA grading system. METHODS: The HRA model consisting of risk
scores (RSs), based on perineural invasion (PI), lymphocytic infiltration (LI),
and worst pattern of invasion (WPOI), was used for grading 80 samples of head and
neck SCC, followed by immunohistochemical staining with antibodies against E
cadherin, N-cadherin, and podoplanin. The two major invasion modes were
considered as epithelial-mesenchymal-transition (EMT) and collective cell
invasion (CCI) with profiles of E-cadherin-/N-cadherin+/podoplanin- and E
cadherin+/N-cadherin-/podoplanin+, respectively. All other immunohistochemical
profiles were classified as partial/incomplete EMT. Statistical analysis was
performed by Kruskal-Wallis and Mann-Whitney U tests (P < 0.05). RESULTS:
Invasion pattern was significantly different among the three RSs (P = 0.01) and
across the different scores of LI (P = 0.03) but not perineural invasion (PNI) (P
= 0.07) and WPOI (P = 0.70). CONCLUSIONS: Based on our results, it seems that
there is a difference in EMT, CCI, and partial/incomplete EMT among the variables
of the HRA model which might help clarify its functioning system.
PMID- 27502396
TI - uPAR enhances malignant potential of triple-negative breast cancer by directly
interacting with uPA and IGF1R.
AB - BACKGROUND: Due to lack of a targeted therapy for the triple-negative breast
cancer (TNBC) patients, it is important to explore this aggressive breast cancer
type in more detail and to establish novel therapeutic approaches. TNBC is
defined negative for the protein expression of oestrogen receptor (ER),
progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2).
One prominent feature of this cancer type is the frequent overexpression of major
components of the urokinase-type plasminogen activator system (uPAS) including
uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as
therapeutic targets. METHODS: Direct interactions of uPAR with interactors were
demonstrated by immunoprecipitations and proximity ligation assays. For stable
knockdowns of target proteins, lentiviral vectors were used and the effects were
analysed by immunoblottings and using in vitro cell viability, migration and
invasion assays. Immunohistochemical and statistical analyses of biomarkers and
clinical parameters were conducted in a TNBC cohort (n = 174). RESULTS: Direct
tumour-promoting interactions of uPAR with uPA and the insulin-like growth factor
receptor 1 (IGF1R) were shown in TNBC cells and these interactions were
significantly reduced (p = 0.001) when uPAR was downregulated. The combined
knockdown of uPAR and uPA or IGF1R additively and significantly reduced cell
viability, migration and invasion of the model cell lines. In TNBC tissue, the
complexes formed by uPAR with uPA or with IGF1R significantly correlated with the
histological grade (p = 0.0019) as well as with cathepsin B and D (p <= 0.0001)
that are implicated in cell invasion and metastasis. CONCLUSIONS: Our outcomes
show that not only overexpressed biomarkers promote tumourigenesis, but rather
their interactions further potentiate tumour progression. This study emphasises
the potential of combined approaches targeting uPAR and its interactors with
regard to an improved therapy of TNBC.
PMID- 27502397
TI - Violacein induces death of RAS-mutated metastatic melanoma by impairing autophagy
process.
AB - Treatment of metastatic melanoma still remains a challenge, since in advanced
stage it is refractory to conventional treatments. Most patients with melanoma
have either B-RAF or N-RAS mutations, and these oncogenes lead to activation of
the RAS-RAF-MEK-ERK and AKT signal pathway, keeping active the proliferation and
survival pathways in the cell. Therefore, the identification of small molecules
that block metastatic cell proliferation and induce cell death is needed.
Violacein, a pigment produced by Chromobacterium violaceum found in Amazon River,
has been used by our group as a biotool for scrutinizing signaling pathways
associated with proliferation, survival, aggressiveness, and resistance of cancer
cells. In the present study, we demonstrate that violacein diminished the
viability of RAS- and RAF-mutated melanoma cells (IC50 value ~500 nM), and more
important, this effect was not abolished after treatment medium removal.
Furthermore, violacein was able to reduce significantly the invasion capacity of
metastatic melanoma cells in 3D culture. In the molecular context, we have shown
for the first time that violacein causes a strong drop on histone deacetylase 6
expression, a proliferating activator, in melanoma cells. Besides, an inhibition
of AXL and AKT was detected. All these molecular events propitiate an inhibition
of autophagy, and consequently, melanoma cell death by apoptosis.
PMID- 27502398
TI - In vitro and in vivo effects of hemodilution on kaolin-based activated clotting
time predicted heparin requirement using a heparin dose-response technique.
AB - PURPOSE: The heparin dose-response (HDR) technique is based on activated clotting
time (ACT) response to a fixed-dose heparin bolus, which varies substantially
among patients. It is unclear, however, whether hemodilution-associated
reductions in coagulation and anticoagulation factors affect the HDR slope.
METHODS: For in vitro hemodilution, aliquots of whole blood from healthy
volunteers were diluted 9:1 and 8:2 v/v with normal saline. For in vivo
hemodilution, a prospective observational study was performed on 46 patients who
underwent elective cardiovascular surgery with or without cardiopulmonary bypass.
HDR slope, antithrombin (AT) activity, complete blood count, and other
coagulation parameters were compared after induction of anesthesia and after
hemodilution with 500 ml of intravenous fluid. RESULTS: In vitro 10 and 20 %
hemodilution significantly increased the HDR slope relative to baseline, reducing
the heparin requirement. Hemodilution of heparinized samples significantly
prolonged ACT, whereas there was no significant change in non-heparinized blood.
The percent changes in fibrinogen and AT activity were significantly greater at
20 % than those of the other coagulation variables. In vivo, hemodilution
significantly increased the HDR slope and reduced heparin requirement. The
percent change in fibrinogen due to hemodilution was significantly greater than
the change in AT activity. Target ACTs of 300 and 450 s were not achieved in 83.3
and 53.8 % of patients, respectively. CONCLUSION: In vitro and in vivo
hemodilution significantly increased the HDR slope and reduced the requirement
for heparin. In vitro, the HDR slope did not change in parallel but became
steeper, depending on the degree of hemodilution.
PMID- 27502399
TI - Size doesn't matter in the heat shock response.
AB - Heat shock factor 1 (Hsf1) is a transcription factor that is often described as
the master regulator of the heat shock response in all eukaryotes. However, due
to its essentiality in yeast, Hsf1's contribution to the transcriptome under
basal and heat shock conditions has never been directly determined. Using a
chemical genetics approach that allowed rapid Hsf1 inactivation, my colleagues
and I have recently shown that the bulk of the heat shock response is Hsf1
independent. Rather than inducing genes responsible for carrying out the various
cellular processes required for adaptation to thermal stress, Hsf1 controls a
dedicated set of chaperone protein genes devoted to restoring protein-folding
homeostasis. The limited scope of the Hsf1 regulon belies its outsize importance
in cellular fitness.
PMID- 27502400
TI - Morbidity and mortality rates after emergency abdominal surgery: an analysis of
4346 patients scheduled for emergency laparotomy or laparoscopy.
AB - PURPOSE: Emergency abdominal surgery results in a high rate of post-operative
complications and death. There are limited data describing the emergency surgical
population in details. We aimed to give a detailed analyses of complications and
mortality in a consecutive group of patients undergoing acute abdominal surgery
over a 4-year period. METHODS: This observational study was conducted between
2009 and 2013 at Copenhagen University Hospital Herlev, Denmark. All patients
scheduled for emergency laparotomy or laparoscopy were included. Pre-, intra-,
and post-operative data were collected from medical records. Complications were
registered according to the Clavien-Dindo classification. Cox regression analysis
was performed to identify risk factors for mortality. RESULTS: A total of 4,346
patients underwent emergency surgery, of whom 14 % had surgical complications and
23 % medical complications. The overall 30-day mortality was 8 % with 50 % of
those in this group over 80 years of age. The 30-day mortality rates were 0.8 %
(95 % CI 0.5-1.1) and 17 % (95 % CI 15.5-18.9), respectively, for the laparoscopy
and the laparotomy groups. The overall death rate within 24 h of surgery was 21
%. Several risk factors for 30- and 90-day mortality were identified: age, ASA
>=3 (American Society of Anaesthesiologists physical status classification),
performance score (Zubroed/WHOclassification), cirrhosis of the liver, chronic
nephropathy, several medical conditions, and malignancy. CONCLUSION: Almost one
in five patients died after emergency laparotomy, of whom one in five died within
24 h of surgery. Predictors for poor outcome were identified.
PMID- 27502402
TI - Endovascular treatment of previously clipped aneurysms: continued evolution of
hybrid neurosurgery.
AB - BACKGROUND/OBJECTIVE: The optimal management of residual or recurrent clipped
aneurysms is infrequently addressed in the literature. METHODS: We reviewed our
endovascular database from January 1998 to May 2016 to identify patients with
clipped aneurysms undergoing subsequent endovascular treatment, evaluating
treatment approach, and clinical and angiographic outcomes. RESULTS: 60 patients
underwent endovascular treatment of residual/recurrent clipped aneurysms; 7
rebled prior to endovascular therapy. Treatment was via coiling alone (n=25,
42%), stent assisted coiling (n=15, 25%), balloon assisted coiling (n=8, 13%),
flow diversion (n=8, 13%), stenting alone (n=3, 5%), or flow diversion with
coiling (n=1, 2%). The procedural permanent neurological morbidity and mortality
rates were 3% and 2%, respectively. Over a clinical follow-up of 253.4 patient
years (median 3.9 years), there was one rebleed in a patient who had declined
further treatment. For 43 patients with at least 1 month of digital subtraction
angiographic follow-up (median 3.4 years), complete aneurysm occlusion was seen
in 79% of cases. Neck remnants were observed in 14%, and stable small dome
remnants were observed in 7% of cases. In a subgroup of 18 patients with 'clip
induced' narrow neck aneurysms, all domes were initially coil occluded (Raymond 1
or 2); there was no permanent procedural morbidity and no aneurysms required
retreatment or recanalized over a median follow-up of 3.9 years. CONCLUSIONS:
Endovascular treatment of residual or recurrent clipped aneurysms is an excellent
treatment approach in well selected patients; 'clip induced' narrow neck
aneurysms fare particularly well after treatment both angiographically and
clinically.
PMID- 27502401
TI - Canalization of gene expression is a major signature of regulatory cold
adaptation in temperate Drosophila melanogaster.
AB - BACKGROUND: Transcriptome analysis may provide means to investigate the
underlying genetic causes of shared and divergent phenotypes in different
populations and help to identify potential targets of adaptive evolution.
Applying RNA sequencing to whole male Drosophila melanogaster from the ancestral
tropical African environment and a very recently colonized cold-temperate
European environment at both standard laboratory conditions and following a cold
shock, we seek to uncover the transcriptional basis of cold adaptation. RESULTS:
In both the ancestral and the derived populations, the predominant characteristic
of the cold shock response is the swift and massive upregulation of heat shock
proteins and other chaperones. Although we find ~25 % of the genome to be
differentially expressed following a cold shock, only relatively few genes (n =
16) are up- or down-regulated in a population-specific way. Intriguingly, 14 of
these 16 genes show a greater degree of differential expression in the African
population. Likewise, there is an excess of genes with particularly strong cold
induced changes in expression in Africa on a genome-wide scale. CONCLUSIONS: The
analysis of the transcriptional cold shock response most prominently reveals an
upregulation of components of a general stress response, which is conserved over
many taxa and triggered by a plethora of stressors. Despite the overall response
being fairly similar in both populations, there is a definite excess of genes
with a strong cold-induced fold-change in Africa. This is consistent with a
detrimental deregulation or an overshooting stress response. Thus, the
canalization of European gene expression might be responsible for the increased
cold tolerance of European flies.
PMID- 27502403
TI - Endovascular treatment for AIS with underlying ICAD.
AB - BACKGROUND: Acute large vessel occlusion (LVO) can result from thromboemboli or
underlying intracranial atherosclerotic disease (ICAD). Although the technique
for revascularization differs significantly for these two lesions (simple
thrombectomy for thromboemboli and balloon angioplasty and stenting for ICAD),
the underlying etiology is often unknown in acute ischemic stroke (AIS).
OBJECTIVE: To evaluate whether procedural complications, revascularization rates,
and functional outcomes differ among patients with LVO from ICAD or
thromboembolism. METHODS: A retrospective review of thrombectomy cases from 2008
to 2015 was carried out for cases of AIS due to underlying ICAD. Thirty-six
patients were identified. A chart and imaging review was performed to determine
revascularization rates, periprocedural complications, and functional outcomes.
Patients with ICAD and acute LVO were compared with those with underlying
thromboemboli. RESULTS: Among patients with ICAD and LVO, mean National
Institutes of Health Stroke Scale (NIHSS) score on admission was 12.9+/-8.5,
revascularization (Thrombolysis In Cerebral Infarction, TICI >=2b) was achieved
in 22/34 (64.7%) patients, 11% had postprocedural intracerebral hemorrhage (PH2),
and 14/33 (42.4%) had achieved a modified Rankin Scale (mRS) score of 0-2 at the
3-month follow-up. Compared with patients without underlying ICAD, there was no
difference in NIHSS on presentation, or in the postprocedural complication rate.
However, procedure times for ICAD were longer (98.5+/-59.8 vs 37.1+/-34.2 min),
there was significant difference in successful revascularization rate between the
groups (p=0.001), and a trend towards difference in functional outcome at 3
months (p=0.07). CONCLUSIONS: Despite AIS with underlying ICAD requiring a more
complex, technically demanding recanalization strategy than traditional
thromboembolic AIS, it appears safe, and good outcomes are obtainable.
PMID- 27502404
TI - Biological Effects of Drug-Free Alginate Beads Cross-Linked by Copper Ions
Prepared Using External Ionotropic Gelation.
AB - External ionotropic gelation offers a unique possibility to entrap multivalent
ions in a polymer structure. The aim of this experimental study was to prepare
new drug-free sodium alginate (ALG) particles cross-linked by Cu2+ ions and to
investigate their technological parameters (particle size, sphericity, surface
topology, swelling capacity, copper content, release of Cu2+ ions,
mucoadhesivity) and biological activity (cytotoxicity and efficiency against the
most common vaginal pathogens-Herpes simplex, Escherichia coli, Candida albicans)
with respect to potential vaginal administration. Beads prepared from NaALG
dispersions (3 or 4%) were cross-linked by Cu2+ ions (0.5 or 1.0 M CuCl2) using
external ionotropic gelation. Prepared mucoadhesive beads with particle size over
1000 MUm exhibited sufficient sphericity (all ?0.89) and copper content (214.8
249.07 g/kg), which increased with concentration of polymer and hardening
solution. Dissolution behaviour was characterized by extended burst effect,
followed by 2 h of copper release. The efficiency of all samples against the most
common vaginal pathogens was observed at cytotoxic Cu2+ concentrations. Anti-HSV
activity was demonstrated at a Cu2+ concentration of 546 mg/L. Antibacterial
activity of beads (expressed as minimum inhibition concentration, MIC) was
influenced mainly by the rate of Cu2+ release which was controlled by the extent
of swelling capacity. Lower MIC values were found for E. coli in comparison with
C. albicans. Sample ALG-3_1.0 exhibited the fastest copper release and was proved
to be the most effective against both bacteria. This could be a result of its
lower polymer concentration in combination with smaller particle size and thus
larger surface area.
PMID- 27502405
TI - Improved Method for Solid Lipid Nanoparticle Preparation Based on Hot
Microemulsions: Preparation, Characterization, Cytotoxicity, and
Hemocompatibility Evaluation.
AB - The ease of application and no requirement of extra energy input make the
microemulsion method favorable for solid lipid nanoparticles (SLNs) production.
Very limited data are available to date on preparation of SLNs from pre-screened
microemulsion phase diagrams. The purpose of this study was to investigate the
microemulsion formation area with solid lipids using hot ternary phase diagrams
at elevated temperatures and to use selected microemulsions for SLN production.
Also, we aimed to characterize obtained SLNs in terms of physicochemical
properties, in vitro cell toxicity, and hemolysis. Phase diagrams of solid lipids
were screened at elevated temperatures and oil-in-water microemulsion regions
were determined. Microemulsions were selected, and SLNs were produced by
modification of the microemulsion dilution method and characterized in terms of
visual appearance, turbidity, particle size, and zeta potential. Cytotoxicity of
nanoparticles was tested on L929 mouse skin fibroblast cells. Hemolytic potential
was assessed in vitro using freshly isolated erythrocytes. The phase diagram
screening and the modified hot microemulsion dilution method enabled production
of SLNs with particle size below 100 nm. We found evidence that the solid lipids
in the SLNs produced by the new method remain in supercooled liquid state.
Nanoparticles prepared by the new method exhibit lower toxicity on L929 cells and
have lower hemolytic potential than the formulations prepared by direct mixing of
the components. The method can be used to prepare SLNs with controllable
composition and small particle size below 100 nm. These SLNs are low toxic and
can be used for drug delivery purposes.
PMID- 27502406
TI - Growth Factor-Loaded Nano-niosomal Gel Formulation and Characterization.
AB - Controlled delivery of signaling factors could be a great approach in the tissue
engineering field. Nano-niosomal drug delivery systems offer numerous advantages
for this purpose. The present study reports the formulation and evaluation of a
growth factor (GF)-loaded nano-niosome-hydrogel composite for GF delivery to
modulate cell behavior. Niosomes were prepared, using span 60 surfactant with
cholesterol (CH) in diethyl ether solvent, by reverse-phase evaporation
technique. Basic fibroblast growth factor (bFGF) and bovine serum albumin (BSA)
were loaded simultaneously and the final suspension was embedded into agarose
hydrogel. Particle size, vesicle morphology, protein entrapment efficiency (EE),
and release profile were measured by dynamic light scattering (DLS) nanoparticle
size analyzer, transmission electron microscopy (TEM) and NanoDrop
spectrophotometry methods, respectively. The release and performance of bFGF were
revealed via human umbilical vein endothelial cell (HUVEC) proliferation using
microscopy imaging and MTT assay. Nano-niosomes had an average particle size of
232 nm and had encapsulated 58% of the total proteins present in the suspension.
bFGF-BSA-loaded niosomal gel considerably enhanced HUVEC proliferation. This GF
loaded niosomal hydrogel could be a potent material in many biomedical
applications including the induction of angiogenesis in tissue engineering.
PMID- 27502407
TI - Development of Microemulsion Delivery System of Essential Oil from Zingiber
cassumunar Roxb. Rhizome for Improvement of Stability and Anti-Inflammatory
Activity.
AB - The present study aims to investigate the major constituents of the essential oil
from Zingiber cassumunar rhizome (EO) and to develop microemulsions with enhanced
chemical stability and anti-inflammatory activity of EO. The major constituents
of EO were terpinen-4-ol (40.5 +/- 6.6%) and sabinene (17.4 +/- 1.4%) as
determined by gas chromatography-mass spectrometry. These compounds were
responsible for the anti-inflammatory activities of EO. Sabinene and terpinen-4
ol significantly reduced nuclear factor-kappa B (NF-kB) expression by 47 +/- 5
and 78 +/- 8%, respectively (p < 0.001) and significantly reduced the interleukin
6 (IL-6) secretion levels to 64 +/- 4% (p < 0.05) and 50 +/- 1% (p < 0.001),
respectively. EO microemulsions, developed using the system of EO/Tween 20 and
propylene glycol (2:1)/water, showed the internal droplet size in the range of
211.5 +/- 63.3 to 366.7 +/- 77.8 nm. Both EO and EO microemulsions were shown to
be safe for human use since there was no apparent toxic effect on human
peripheral blood mononuclear cells. Interestingly, EO microemulsion could
significantly protect sabinene from the evaporation after heating-cooling
stability test, which leads to a good stability and high efficacy. Moreover, EO
microemulsions significantly enhanced the anti-inflammatory effect comparing to
the native EO. Therefore, microemulsions were attractive delivery system for
natural anti-inflammatory compounds since they could enhance both efficacy and
stability of EO.
PMID- 27502408
TI - Electronic data capture on athletes' pre-participation health and in-competition
injury and illness at major sports championships: An extended usability study in
Athletics.
AB - This study set out to identify factors critical for the usability of electronic
data collection in association with championships in individual sports. A
qualitative analysis of electronic data collection system usability for
collection of data on pre-participation health from athletes and in-competition
injury and illness from team physicians was performed during the 2013 European
Athletics Indoor Championships. A total of 15 athletes and team physicians
participated. Athletes were found to experience few problems interacting with the
electronic data collection system, but reported concerns about having to reflect
on injury and illness before competitions and the medical terminology used. Team
physicians encountered problems when first navigating through the module for
clinical reporting, but they were not subjected to motivational problems. We
conclude that athletes' motivation to self-report health data and the design of
the human-computer interface for team physicians are key issues for the usability
of electronic data collection systems in association with championships in
individual sports.
PMID- 27502409
TI - Neonatal encephalocardiomyopathy caused by mutations in VARS2.
AB - VARS2 encodes a mitochondrial aminoacyl-tRNA-synthetase. Mutations in VARS2 have
recently been identified as a cause of mitochondrial encephalomyopathy in three
individuals. However, clinical information remained scarce. Exome sequencing lead
us to identify compound heterozygous pathogenic VARS2 variants in a boy
presenting with severe lactic acidosis, hypertrophic cardiomyopathy, epilepsy,
and abnormalities on brain imaging including hypoplasia of corpus callosum and
cerebellum as well as a massive lactate peak on MR-spectroscopy. Studies in
patient-derived fibroblasts confirmed the functional relevance of the identified
VARS2 variants. Our report expands the phenotypic spectrum associated with this
rare mitochondrial defect, in that VARS2 deficiency may also cause severe
neonatal presentations with cardiac involvement and structural brain
abnormalities.
PMID- 27502411
TI - Use of food labels by adolescents to make healthier choices on snacks: a cross
sectional study from Sri Lanka.
AB - BACKGROUND: Unhealthy snacking is commonly seen among adolescents. Therefore, use
of food labels is promoted for making healthier choices on packaged snacks. This
study was conducted to assess the use of food labels in making choices on
packaged snack and its associated factors among adolescents. METHODS: A cross
sectional study was conducted in 2012 among 542 Grade 12 students in Sri Lanka.
Eight classes were selected as 'clusters' for the study (two classes each from
two schools that were selected randomly from each list of 'Girls only' and 'Boys
only' schools in Colombo district). A self-administered questionnaire assessed
their socio-demography, snacking behaviour, attitudes and nutrition knowledge
related to food labels. Adolescents' use of labels was assessed by three
practices (label reading frequency, attention paid to label contents and correct
interpretation of six hypothetical labels of snacks). Based on total scores
obtained for the three practices, 'satisfactory' (score >=75(th) percentile mark)
and 'unsatisfactory' (score <75(th) percentile mark) label users were identified.
Using SPSS, associations were assessed at 0.05 significance level using Chi
square-test. RESULTS: Of the participants, 51 % were males; 61 % spent their
pocket money at least once/week on packaged snacks; predominantly on biscuits (85
%) and cola-drinks (77 %) and 88 % selected snacks on their own. The majority
(74.5 %) was frequent ('always' or 'most often') label readers with female
predominance (p < 0.05). Over 74 % paid attention frequently to the brand name
(75 %), price (85 %) and nutrition panel (81 %). Over 64 % were able to select
the better food label when given a choice between two snacks, although some did
it for reasons such as attractive label (63 %). The majority (84 %) had good
knowledge (obtaining more than the 75(th) percentile mark) on interpreting
labels. Although not statistically significant, 'unsatisfactory' label use was
higher among males (73 %), purchasing power (70.4 %) and unhealthy snacking
behaviour (73 %). In contrast, among the marketing strategies, identifying known
brands (73.2 %) and imported products (75.8 %) as 'good' products were
significantly associated with 'unsatisfactory' label use (p < 0.05). CONCLUSIONS:
Despite having good knowledge and positive attitudes, food label use is
unsatisfactory among adolescents. Skills in reading labels should be addressed in
the 'School canteen policy' in Sri Lanka.
PMID- 27502410
TI - The serum zinc concentration as a potential biological marker in patients with
major depressive disorder.
AB - Despite many clinical trials assessing the role of zinc in major depressive
disorder (MDD), the conclusions still remain ambiguous. The aim of the present
clinical study was to determine and comparison the zinc concentration in the
blood of MDD patients (active stage or remission) and healthy volunteers
(controls), as well as to discuss its potential clinical usefulness as a
biomarker of the disease. In this study 69 patients with current depressive
episode, 45 patients in remission and 50 controls were enrolled. The zinc
concentration was measured by electrothermal atomic absorption spectrometry (ET
AAS). The obtained results revealed, that the zinc concentration in depressed
phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06
mg/L, respectively], while the zinc level in patients achieve remission was not
significantly different from the controls [1.07 vs. 1.06 mg/L, respectively].
Additionally, among the patients achieve remission a significant differences in
zinc concentration between group with and without presence of drug-resistance in
the previous episode of depression were observed. Also, patients in remission
demonstrated correlation between zinc level and the average number of depressive
episodes in the last year. Serum zinc concentration was not dependent on atypical
features of depression, presence of psychotic symptoms or melancholic syndrome,
age, age of onset or duration of disease, number of episodes in the life time,
duration of the episode/remission and severity of depression measured by the
Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression
Rating Scale (MADRS). Concluding, our findings confirm the correlation between
zinc deficit present in the depressive episode, and are consistent with the
majority of previous studies. These results may also indicate that serum zinc
concentration might be considered as a potential biological marker of MDD.
PMID- 27502412
TI - Accumulation of Copper in Gill, Liver, Spleen, Kidney and Muscle Tissues of
Clarias gariepinus Exposed to the Metal Singly and in Mixture with Chitosan.
AB - Accumulation of copper (Cu), applied singly and in mixture with chitosan (CT), in
gill, liver, spleen, kidney and muscle tissues of Clarias gariepinus was studied
after exposing the fish to no Cu (control), 5 ppm Cu, 5 ppm Cu + 75 ppm CT
mixture over 1, 7 and 15 days. Metal levels in tissues were determined using an
ICP-AES spectrophotometer. No mortality was observed during the experiments.
Highest accumulation of Cu was observed in liver while lowest accumulation was
observed in muscle tissue. Exposure to Cu-CT mixture decreased Cu accumulation in
liver at all exposure periods and in kidney on the 15th day compared to Cu alone.
Exposure to Cu alone and Cu-CT mixture had no effect on Cu accumulation in spleen
or muscle tissue. Copper accumulation increased in gill tissue compared to
control when exposed to Cu alone at all exposure periods, and exposure to the Cu
CT mixture significantly increased Cu accumulation in this tissue at all exposure
periods compared to Cu alone.
PMID- 27502413
TI - High-frequency rTMS on leg motor area in the early phase of stroke.
AB - Although repetitive transcranial magnetic stimulation (rTMS) for upper limb motor
area in stroke patients is beneficial, it has been poorly investigated in rTMS
for leg motor area. Furthermore, no study has examined the usefulness of rTMS for
leg motor area in patients in the early phase of stroke. Twenty-one patients with
a hemispheric stroke lesion in the early phase were randomly assigned into two
groups: the high-frequency (HF)-rTMS group [N = 11] and the sham stimulation
group [N = 10]. Patients received rTMS for 5 consecutive days, beginning 10.9 +/-
6.6 days on average after the onset. Brunnstrom Recovery Stages (BRS) for the
lower limbs and the Ability for Basic Movement Scale Revised (ABMS II) were
assessed before and after the intervention. The improvement in BRS for the lower
limbs was significant after the intervention in the HF-rTMS group. Although both
the HF-rTMS and sham stimulation groups had significant improvements in ABMS II
scores, the extent of improvement in the AMBS II was significantly greater in the
HF-rTMS group than in the sham stimulation group. Application of HF-rTMS over the
bilateral leg motor areas has potential to be a new rehabilitation therapy for
patients in the acute phase of stroke.
PMID- 27502414
TI - Recent advances on halohydrin dehalogenases-from enzyme identification to novel
biocatalytic applications.
AB - Halohydrin dehalogenases are industrially relevant enzymes that catalyze the
reversible dehalogenation of vicinal haloalcohols with formation of the
corresponding epoxides. In the reverse reaction, also other negatively charged
nucleophiles such as azide, cyanide, or nitrite are accepted besides halides to
open the epoxide ring. Thus, novel C-N, C-C, or C-O bonds can be formed by
halohydrin dehalogenases, which makes them attractive biocatalysts for the
production of various beta-substituted alcohols. Despite the fact that only five
individual halohydrin dehalogenase enzyme sequences have been known until
recently enabling their heterologous production, a large number of different
biocatalytic applications have been reported using these enzymes. The recent
characterization of specific sequence motifs has facilitated the identification
of novel halohydrin dehalogenase sequences available in public databases and has
largely increased the number of recombinantly available enzymes. These will help
to extend the biocatalytic repertoire of this enzyme family and to foster novel
biotechnological applications and developments in the future. This review gives a
general overview on the halohydrin dehalogenase enzyme family and their
biochemical properties and further focuses on recent developments in halohydrin
dehalogenase biocatalysis and protein engineering.
PMID- 27502415
TI - Antimicrobial properties and death-inducing mechanisms of saccharomycin, a
biocide secreted by Saccharomyces cerevisiae.
AB - We recently found that Saccharomyces cerevisiae (strain CCMI 885) secretes
antimicrobial peptides (AMPs) derived from the glycolytic enzyme glyceraldehyde 3
phosphate dehydrogenase (GAPDH) that are active against various wine-related
yeast and bacteria. Here, we show that several other S. cerevisiae strains also
secrete natural biocide fractions during alcoholic fermentation, although at
different levels, which correlates with the antagonistic effect exerted against
non-Saccharomyces yeasts. We, therefore, term this biocide saccharomycin. The
native AMPs were purified by gel-filtration chromatography and its antimicrobial
activity was compared to that exhibited by chemically synthesized analogues (AMP1
and AMP2/3). Results show that the antimicrobial activity of the native AMPs is
significantly higher than that of the synthetic analogues (AMP1 and AMP2/3), but
a conjugated action of the two synthetic peptides is observed. Moreover, while
the natural AMPs are active at pH 3.5, the synthetic peptides are not, since they
are anionic and cannot dissolve at this acidic pH. These findings suggest that
the molecular structure of the native biocide probably involves the formation of
aggregates of several peptides that render them soluble under acidic conditions.
The death mechanisms induced by the AMPs were also evaluated by means of
epifluorescence microscopy-based methods. Sensitive yeast cells treated with the
synthetic AMPs show cell membrane disruption, apoptotic molecular markers, and
internalization of the AMPs. In conclusion, our work shows that saccharomycin is
a natural biocide secreted by S. cerevisiae whose activity depends on the
conjugated action of GAPDH-derived peptides. This study also reveals that S.
cerevisiae secretes GAPDH-derived peptides as a strategy to combat other
microbial species during alcoholic fermentations.
PMID- 27502416
TI - Influence of cAMP receptor protein (CRP) on bacterial virulence and
transcriptional regulation of allS by CRP in Klebsiella pneumoniae.
AB - cAMP receptor protein (CRP) is one of the most important transcriptional
regulators, which can regulate large quantities of operons in different bacteria.
The gene allS was well-known as allantoin-utilizing capability and involving in
bacterial virulence in Klebsiella pneumoniae (K. pneumoniae). The specific DNA
recognition motif of transcription regulator CRP was found in allS promoter
region. Therefore, this study is aimed to investigate the function of CRP on
virulence and its transcriptional regulation mechanism to gene allS in K.
pneumoniae. The wild-type (WT) K. pneumoniae NTUH-2044, crp knockout (Kp
Deltacrp) and the complemented knockout (KpC-Deltacrp) strains were used to
determine the function of crp gene. The lacZ fusion, qRT-PCR, electrophoretic
mobility shift and DNase I footprinting assays were performed to study the
transcriptional regulation of CRP on allS. The result showed a decreased
virulence in crp knockout strain. Complement through supplementing crp fragment
in expression plasmid partially restore virulence of knockout bacteria. The CRP
could bind to the allS promoter-proximal region and the binding site was further
refined to be located from 60bp to 94bp upstream of the allS promoter. Based on
these results, we proposed that CRP is an essential virulence regulator and knock
out of crp gene will result in reduced virulence in K. pneumoniae. In the
meantime, the transcription of gene allS is positively regulated by CRP via
directly binding to upstream of allS promoter.
PMID- 27502417
TI - Intrinsic HER4/4ICD transcriptional activation domains are required for STAT5A
activated gene expression.
AB - The epidermal growth factor receptor family member HER4 undergoes proteolytic
processing at the cell surface to release the HER4 intracellular domain (4ICD)
nuclear protein. Interestingly, 4ICD directly interacts with STAT5 and functions
as an obligate STAT5 nuclear chaperone. Once in the nucleus 4ICD binds with STAT5
at STAT5 target genes, dramatically potentiating STAT5 transcriptional
activation. These observations raise the possibility that 4ICD directly
coactivates STAT5 gene expression. Using both yeast and mammalian transactivation
reporter assays, we performed truncations of 4ICD fused to a GAL4 DNA binding
domain and identified two independent 4ICD transactivation domains located
between residues 1022 and 1090 (TAD1) and 1192 and 1225 (TAD2). The ability of
the 4ICD DNA binding domain fusions to transactivate reporter gene expression
required deletion of the intrinsic tyrosine kinase domain. In addition, we
identified the 4ICD carboxyl terminal TVV residues, a PDZ domain binding motif
(PDZ-DBM), as a potent transcriptional repressor. The transactivation activity of
the HER4 carboxyl terminal domain lacking the tyrosine kinase (CTD) was
significantly lower than similar EGFR or HER2 CTD. However, deletion of the HER4
CTD PDZ-DBM enhanced HER4 CTD transactivation to levels equivalent to the EGFR
and HER2 CTDs. To determine if 4ICD TAD1 and TAD2 have a physiologically relevant
role in STAT5 transactivation, we coexpressed 4ICD or 4ICD lacking TAD2 or both
TAD1 and TAD2 with STAT5 in a luciferase reporter assay. Our results demonstrate
that each 4ICD TAD contributes additively to STAT5A transactivation and the
ability of STAT5A to transactivate the beta-casein promoter requires the 4ICD
TADs. Taken together, published data and our current results demonstrate that
both 4ICD nuclear chaperone and intrinsic coactivation activities are essential
for STAT5 regulated gene expression.
PMID- 27502418
TI - Identification of AaCASPS7, an effector caspase in Aedes albopictus.
AB - Aedes albopictus mosquito is a vector of various arboviruses and is becoming a
significant threat to public health due to its rapid global expansion. Several
reports suggest that apoptosis could be a factor limiting arbovirus infection in
mosquitoes. Thus, it is significant to identify apoptosis pathway and study the
correlation between apoptosis and virus infection in mosquitoes. Apoptosis is a
type of programmed cell death that plays a vital role in immunity, development,
and tissue homeostasis. Caspases are a family of conserved proteases playing
important roles in apoptosis. In this study, we identified Aedes albopictus
AaCASPS7, a caspase shared high identity with dipteran insect drICE orthologs.
Phylogenetic analysis showed the closest relative of AaCASPS7 was Aedes aegypti
AeCASPS7. AaCASPS7 displayed several features that were typical of an effector
caspase and showed significant activity to effector caspase substrates. Aacasps7
transcripts were expressed ubiquitously in developmental and adult stages in
Aedes albopictus mosquitoes. Transient expression of AaCASPS7 induced caspase
dependent apoptosis in C6/36 cells. Taken together the above data, this study
identified a novel caspase, AaCASPS7, which might function as an apoptotic
caspase. Further study the function of AaCASPS7 would facilitate better
understanding the apoptotic mechanism in Aedes albopictus mosquito.
PMID- 27502419
TI - Response of the JAK-STAT signaling pathway to oxygen deprivation in the red eared
slider turtle, Trachemys scripta elegans.
AB - The red-eared slider turtle, Trachemys scripta elegans, is a model organism
commonly used to study the environmental stress of anoxia. It exhibits multiple
biochemical adaptations to ensure its survival during the winter months where
quantities of oxygen are largely depleted. We proposed that JAK-STAT signaling
would display stress responsive regulation to mediate the survival of the red
eared slider turtle, Trachemys scripta elegans, during anoxic stress.
Importantly, the JAK-STAT signaling pathway is involved in transmitting
extracellular signals to the nucleus resulting in the expression of select genes
that aid cell survival and growth. Immunoblotting was used to compare the
relative phosphorylation levels of JAK proteins, STAT proteins, and two of its
inhibitors, SOCS and PIAS, in response to anoxia. A clear activation of the JAK
STAT pathway was observed in the liver tissue while no significant changes were
found in the skeletal muscle. To further support our findings we also found an
increase in mRNA transcripts of downstream targets of STATs, namely bcl-xL and
bcl-2, using PCR analysis in the liver tissues. These findings suggest an
important role for the JAK-STAT pathway in exhibiting natural anoxia tolerance by
the red-eared slider turtle.
PMID- 27502421
TI - Novel cellulose-collagen blend biofibers prepared from an amine/salt solvent
system.
AB - Cellulose/collagen biofibers were produced from ethylene diamine/potassium
thiocyanate binary solvent system, with methanol as a coagulant. The dynamic
viscosity of the solutions decreased with the gradual increase in the collagen
content up to 40%. The elemental analysis showed incorporation of collagen into
cellulose matrix, thereby demonstrating some degree of interaction with the
cellulose matrix. The chemical and thermal analysis further revealed an
intermolecular interaction between cellulose and the protein and improved thermal
stability, respectively. Furthermore, the electron microscopy images mostly
exhibited fibrillar morphology with no visible phase separation, indicating
compatibility between the two phases. Moreover, biofibers containing higher
cellulose content showed higher crystallinity, tensile, and birefringence
properties of the composite fibers.
PMID- 27502422
TI - Transubstantiating commercial mushroom market with ultrasonically ultrasized
mushroom powders showcasing higher bioactivity.
AB - Mushrooms that have been restricted to fresh markets have now entered commercial
and pharmaceutical markets. However, not much research has been targeted on
testing the efficiency of these commercialized mushroom powders or capsules. For
the first time, efforts were made to study the bioactive properties and
antimicrobial properties of four predominant mushroom capsules available for
commercial purposes. Then, these commercial mushroom powders were downsized to
ultrasized fine powders by sonication and then their properties were compared
against the commercialized ones. The results indicated that the bioactive
properties and the antioxidant properties of these powders when used as marketed
capsules was very less. It was following ultrasonication assisted size reduction
that the cumulative bioactivity related properties got accelerated. Micro size
reduction of the mushroom powders lead to significant enhancement of antiviral
properties compared to antibacterial and antifungal properties. This work
demonstrates that commercialization of mushroom as powders could realize higher
impact through sonication assisted ultrasizing and even nanosizing.
PMID- 27502424
TI - Risk Factors and Outcome Analysis in Children with Carbon Monoxide Poisoning.
AB - BACKGROUND: Carbon monoxide (CO) poisoning is one of the common causes of
poisoning in patients and can result in significant morbidity and mortality.
However, few studies have focused on the pediatric group. METHODS: We
retrospectively reviewed children (age < 18 years) with CO poisoning from nonfire
accidents at a tertiary medical center in Taiwan from 2002 to 2010. We analyzed
the patients' characteristics, management, and outcome; compared the data of
patients who received hyperbaric oxygen (HBO) to those who received normobaric
oxygen (NBO) therapy; and identified the ri0sk factors for patients who developed
delayed neurological sequelae (DNS) or permanent neurological sequelae (PNS).
RESULTS: A total of 81 children were enrolled. The annual case number increased
from five cases in 2002 to 20 in 2010, particularly during the cold months
(December to February). The most common source of exposure was an indoor heating
system (54.3%). The most common presenting symptoms were vomiting (32.1%) and
consciousness changes (30.9%). HBO treatment tended to be administered to
patients with a higher initial COHb (%) (p < 0.001), an initial Glasgow coma
scale change (p < 0.001), and admission to the hospital (p = 0.002). After
multivariate analysis, treatment in the intensive care unit because of prolonged
loss of consciousness (p = 0.002) was the only independent risk factor for
patients with DNS; only rescue by a ventilator (p < 0.001) was an independent
risk factor for patients with PNS. In comparison to the NBO therapy, HBO
treatment did not show benefit or harm to patients according to the incidence of
inducing DNS or PNS after multivariate analysis. CONCLUSION: For those with
treatment in the intensive care unit because of prolonged loss of consciousness
and rescue by a ventilator, special attention should be given and follow-up
should be performed to determine whether DNS or PNS occurs, particularly epilepsy
and cognitive deficits.
PMID- 27502420
TI - Nuclear retinoid receptors and pregnancy: placental transfer, functions, and
pharmacological aspects.
AB - Animal models of vitamin A (retinol) deficiency have highlighted its crucial role
in reproduction and placentation, whereas an excess of retinoids (structurally or
functionally related entities) can cause toxic and teratogenic effects in the
embryo and foetus, especially in the first trimester of human pregnancy. Knock
out experimental strategies-targeting retinoid nuclear receptors RARs and RXRs
have confirmed that the effects of vitamin A are mediated by retinoic acid
(especially all-trans retinoic acid) and that this vitamin is essential for the
developmental process. All these data show that the vitamin A pathway and
metabolism are as important for the well-being of the foetus, as they are for
that of the adult. Accordingly, during this last decade, extensive research on
retinoid metabolism has yielded detailed knowledge on all the actors in this
pathway, spurring the development of antagonists and agonists for therapeutic and
research applications. Natural and synthetic retinoids are currently used in
clinical practice, most often on the skin for the treatment of acne, and as anti
oncogenic agents in acute promyelocytic leukaemia. However, because of the
toxicity and teratogenicity of retinoids during pregnancy, their pharmacological
use needs a sound knowledge of their metabolism, molecular aspects, placental
transfer, and action.
PMID- 27502426
TI - A PROCESS OF PRIORITIZING TOPICS FOR HEALTH TECHNOLOGY ASSESSMENT IN KAZAKHSTAN.
AB - OBJECTIVES: The aim of this study was to develop criteria for the prioritization
of topics for health technology assessment (HTA) in the healthcare system of
Kazakhstan. METHODS: Initial proposals for criteria were suggested through
consultation with Ministry of Health (MoH) policy areas. These were refined
through a workshop attended by HTA department staff, persons from medical
universities and research institutes, and MoH policy makers. The workshop
included discussion on methods used in international HTA practice. Opinions of
participants on selection of criteria from those specified in a review of
prioritization processes were used to define a list for inclusion in an
instrument for routine use. A scoring system was established in later discussion.
RESULTS: Selected criteria for HTA prioritization were burden of disease,
availability of alternative technology, clinical effectiveness, economic
efficiency, budget impact, and ethical, legal, and/or psychosocial aspects. For
each criterion, a health technology under consideration is given a score from 3
(High) to 1 (Low). The total score determines whether the technology is of high
to medium priority or of low priority. Determination of priorities for
assessment, using the instrument, should be carried out by an expert group
appointed by the MoH. The process was applied in 2014 to a selection of topics,
and three health technologies were chosen for full assessments. CONCLUSIONS:
Criteria for prioritization have evolved with development of the HTA program in
Kazakhstan. A method for HTA prioritization has been developed that is easy to
apply, requires comparatively few resources, and is compatible with processes
required by the MoH.
PMID- 27502425
TI - Olfactory perception of chemically diverse molecules.
AB - BACKGROUND: Understanding the relationship between a stimulus and how it is
perceived reveals fundamental principles about the mechanisms of sensory
perception. While this stimulus-percept problem is mostly understood for color
vision and tone perception, it is not currently possible to predict how a given
molecule smells. While there has been some progress in predicting the
pleasantness and intensity of an odorant, perceptual data for a larger number of
diverse molecules are needed to improve current predictions. Towards this goal,
we tested the olfactory perception of 480 structurally and perceptually diverse
molecules at two concentrations using a panel of 55 healthy human subjects.
RESULTS: For each stimulus, we collected data on perceived intensity,
pleasantness, and familiarity. In addition, subjects were asked to apply 20
semantic odor quality descriptors to these stimuli, and were offered the option
to describe the smell in their own words. Using this dataset, we replicated
several previous correlations between molecular features of the stimulus and
olfactory perception. The number of sulfur atoms in a molecule was correlated
with the odor quality descriptors "garlic," "fish," and "decayed," and large and
structurally complex molecules were perceived to be more pleasant. We discovered
a number of correlations in intensity perception between molecules. We show that
familiarity had a strong effect on the ability of subjects to describe a smell.
Many subjects used commercial products to describe familiar odorants,
highlighting the role of prior experience in verbal reports of olfactory
perception. Nonspecific descriptors like "chemical" were applied frequently to
unfamiliar odorants, and unfamiliar odorants were generally rated as neither
pleasant nor unpleasant. CONCLUSIONS: We present a very large psychophysical
dataset and use this to correlate molecular features of a stimulus to olfactory
percept. Our work reveals robust correlations between molecular features and
perceptual qualities, and highlights the dominant role of familiarity and
experience in assigning verbal descriptors to odorants.
PMID- 27502427
TI - Abnormal auditory pattern perception in schizophrenia.
AB - Mismatch negativity (MMN) in response to deviation from physical sound parameters
(e.g., pitch, duration) is reduced in individuals with long-term schizophrenia
(Sz), suggesting deficits in deviance detection. However, MMN can appear at
several time intervals as part of deviance detection. Understanding which part of
the processing stream is abnormal in Sz is crucial for understanding MMN
pathophysiology. We measured MMN to complex pattern deviants, which have been
shown to produce multiple MMNs in healthy controls (HC). Both simple and complex
MMNs were recorded from 27 Sz and 27 matched HC. For simple MMN, pitch- and
duration-deviants were presented among frequent standard tones. For complex MMN,
patterns of five single tones were repeatedly presented, with the occasional
deviant group of tones containing an extra sixth tone. Sz showed smaller pitch
MMN (p=0.009, ~110ms) and duration MMN (p=0.030, ~170ms) than healthy controls.
For complex MMN, there were two deviance-related negativities. The first (~150ms)
was not significantly different between HC and SZ. The second was significantly
reduced in Sz (p=0.011, ~400ms). The topography of the late complex MMN was
consistent with generators in anterior temporal cortex. Worse late MMN in Sz was
associated with increased emotional withdrawal, poor attention, lack of
spontaneity/conversation, and increased preoccupation. Late MMN blunting in
schizophrenia suggests a deficit in later stages of deviance processing.
Correlations with negative symptoms measures are preliminary, but suggest that
abnormal complex auditory perceptual processes may compound higher-order
cognitive and social deficits in the disorder.
PMID- 27502428
TI - Targeted Anterior Gland Focal Therapy-a Novel Treatment Option for a Better
Defined Disease.
AB - The goal of focal therapy is to achieve long-term oncological control by
eradicating only the clinically significant focus/foci of cancer within the
prostate, while preserving erectile function and continence. Anterior prostate
cancers may have a PZ or TZ origin and share commonalities in location and
biology. While anterior prostate cancers previously constituted a diagnostic
blind spot in the prostate and were often not detected or discovered late, with
the rapid dissemination of advanced imaging and biopsy techniques, they can now
be identified at an earlier, organ-confined stage due to MR imaging and targeted
biopsies. Due to their anterior location, they represent a therapeutic target
that allows for thorough ablation of the cancer focus/foci with an adequate
margin while remaining far from the neurovascular bundles bilaterally. However,
the TZ origin cancers are mostly anterior to the distal urethra close to the apex
and the striated sphincter. Men having early stage anterior cancers may represent
good candidates to achieve a balance between oncological control and functional
preservation with focal therapy. Thus, this class of tumor based on location,
along with the proposed treatment, represents a novel form of targeted image
guided therapy.
PMID- 27502430
TI - Rescuing neuronal cell death by RAIDD- and PIDD- derived peptides and its
implications for therapeutic intervention in neurodegenerative diseases.
AB - Caspase-2 is known to be involved in oxidative-stress mediated neuronal cell
death. In this study, we demonstrated that rotenone-induced neuronal cell death
is mediated by caspase-2 activation via PIDDosome formation. Our newly designed
TAT-fused peptides, which contains wild-type helix number3 (H3) from RAIDD and
PIDD, blocked the PIDDosome formation in vitro. Furthermore, peptides inhibited
rotenone-induced caspase-2-dependent apoptosis in neuronal cells. These results
suggest that PIDD- or RAIDD-targeted peptides might be effective at protecting
against rotenone-induced neurotoxicity. Our peptides are novel neuronal cell
apoptosis inhibitors that might serve as a prototype for development of drugs for
the treatment of neurodegenerative diseases.
PMID- 27502431
TI - Intensity-modulated radiotherapy for early glottic cancer: transition to a new
standard of care?
AB - For decades, the standard of care for radiation treatment of early larynx cancers
has been conventional treatment using opposed lateral fields encompassing the
larynx and overlying neck structures, including the adjacent carotid arteries.
While intensity-modulated radiotherapy (IMRT) has replaced conventional
radiotherapy for all other head/neck cancer situations, the use of IMRT to treat
early glottic cancers remains controversial. The article reviews the published
experience with IMRT for this clinical situation and provides a detailed review
of the literature on radiation-induced carotid toxicity and how it might apply to
the controversy. Finally, we discuss whether the radiation oncology community
should transition to IMRT as a new standard of care for the treatment of early
glottic cancers.
PMID- 27502429
TI - Genetics of Male Infertility.
AB - While 7 % of the men are infertile, currently, a genetic etiology is identified
in less than 25 % of those men, and 30 % of the infertile men lack a definitive
diagnosis, falling in the "idiopathic infertility" category. Advances in genetics
and epigenetics have led to several proposed mechanisms for male infertility.
These advances may result in new diagnostic tools, treatment approaches, and
better counseling with regard to treatment options and prognosis. In this review,
we focus on clinical aspects of male infertility and the role of genetics in
elucidating etiologies and the potential of treatments.
PMID- 27502432
TI - Long-term effectiveness and safety of once-daily, single-entity, extended-release
hydrocodone in patients of >=75 years of age with moderate to severe nonmalignant
and nonneuropathic pain.
AB - In elderly (>=75 years) individuals, age-associated physiologic changes and a
higher prevalence of comorbidities, polypharmacy, and increased susceptibility to
medication-induced side effects complicate pain management. Hysingla(r) ER (HYD)
is a once-daily, single-entity, extended-release hydrocodone formulation approved
for the treatment of chronic pain that is insufficiently controlled by
alternative treatments. In this post-hoc analysis of a previously reported study,
the effectiveness and safety of HYD for the treatment of moderate-to-severe
chronic pain among the elderly (>=75 years) for a 52-week duration was
investigated. HYD dose administered during the maintenance period-remained
relatively stable and provided clinically meaningful decreases in mean "pain over
the last 24 h" and pain interference scores. Patients achieved pain control
without additional non-study opioid use at the end of the study. Adverse events
were typical of opioids. In summary, HYD provided clinically meaningful reduction
of pain scores in elderly patients that were maintained over a 52-week period.
PMID- 27502433
TI - Effect of long-term combined application of organic and inorganic fertilizers on
soil nematode communities within aggregates.
AB - A long-term fertilization experiment was conducted to examine the effects of
different fertilization practices on nematode community composition within
aggregates in a wheat-maize rotation system. The study was a randomized complete
block design with three replicates. The experiment involved the following four
treatments: no fertilizer, inorganic N, P and K fertilizer (NPK), NPK plus manure
(NPKM) and NPK plus maize straw (NPKS). Soil samples were taken at 0-20 cm depth
during the wheat harvest stage. Based on our results, NPKS contributed to soil
aggregation and moisture retention, with a positive effect on soil total nitrogen
accumulation, particularly within small macroaggregates (0.25-1 mm) and
microaggregates (<0.25 mm). The C/N ratio was correlated to the distribution of
the soil nematode community. Both manure application and straw incorporation
increased the nematode functional metabolic footprints within all aggregates.
Additionally, the functional metabolic footprints decreased with a decline in
aggregate size. The accumulation of total nitrogen within <1 mm aggregates under
NPKS might play a key role in maintaining the survival of soil nematodes. In our
study, both crop straw incorporation and inorganic fertilizer application
effectively improved soil physicochemical properties and were also beneficial for
nematode survival within small aggregate size fractions.
PMID- 27502434
TI - Partial redundancy and functional specialization of E-class SEPALLATA genes in an
early-diverging eudicot.
AB - Plant MADS-box genes have duplicated extensively, allegedly contributing to the
immense diversity of floral form in angiosperms. In Arabidopsis thaliana (a core
eudicot model plant), four SEPALLATA (SEP) genes comprise the E-class from the
extended ABCE model of flower development. They are redundantly involved in the
development of the four types of floral organs (sepals, petals, stamens and
carpels) and in floral meristem determinacy. E-class genes have been examined in
other core eudicots and monocots, but have been less investigated in non-core
eudicots. Our goal was to functionally characterize the E-class genes in the
early-diverging eudicot Thalictrum thalictroides (Ranunculaceae), whose flowers
are apetalous. We identified four SEP orthologs, which when placed in a
phylogenetic context, resulted from a major gene duplication event before the
origin of angiosperms and a subsequent duplication at the origin of the
Ranunculales. We used Virus-Induced Gene Silencing (VIGS) to down-regulate the
three expressed paralogs individually and in combination to investigate their
function and to determine the degree of conservation versus divergence of this
important plant transcription factor. All loci were partially redundant in sepal
and stamen identity and in promoting petaloidy of sepals, yet the SEP3 ortholog
had a more pronounced role in carpel identity and development. The two other
paralogs appear to have subfunctionalized in their cadastral roles to keep the
boundaries between either sepal and stamen zones or stamen and carpel zones.
Double knockdowns had enhanced phenotypes and the triple knockdown had an even
more severe phenotype that included partial to complete homeotic conversion of
stamens and carpels to sepaloid organs and green sepals, highlighting a role of E
class genes in petaloidy of sepals in this species. While no floral meristem
determinacy defects were observed, this could be due to residual amounts of gene
expression in the VIGS experiments being sufficient to perform this function or
to the masking role of a redundant gene.
PMID- 27502435
TI - Functional constraints on SoxE proteins in neural crest development: The
importance of differential expression for evolution of protein activity.
AB - Vertebrate SoxE genes (Sox8, 9, and 10) are key regulators of neural crest cell
(NCC) development. These genes arose by duplication from a single SoxE gene in
the vertebrate ancestor. Although SoxE paralogs are coexpressed early in NCC
development, later, Sox9 is restricted to skeletogenic lineages in the head, and
Sox10 to non-skeletogenic NCC in the trunk and head. When this
subfunctionalization evolved and its possible role in the evolution of the neural
crest are unknown. Sea lampreys are basal vertebrates that also possess three
SoxE genes, while only a single SoxE is present in the cephalochordate amphioxus.
In order to address the functional divergence of SoxE genes, and to determine if
differences in their biochemical functions may be linked to changes in neural
crest developmental potential, we examined the ability of lamprey and amphioxus
SoxE genes to regulate differentiation of NCC derivatives in zebrafish colourless
(cls) mutants lacking expression of sox10. Our findings suggest that the proto
vertebrate SoxE gene possessed both melanogenic and neurogenic capabilities prior
to SoxE gene duplication. Following the agnathan-gnathostome split, lamprey SoxE1
and SoxE3 largely lost their melanogenic and/or enteric neurogenic properties,
while gnathostome SoxE paralogs have retained functional conservation. We posit
that this difference in protein subfunctionalization is a direct consequence of
the independent regulation of SoxE paralog expression between the two lineages.
Specifically, we propose that the overlapping expression of gnathostome SoxE
paralogs in early neural crest largely constrained the function of gnathostome
SoxE proteins. In contrast, the largely non-overlapping expression of lamprey
SoxE paralogs allowed them to specialize with regard to their DNA-binding and/or
protein interaction properties. Restriction of developmental potential among
cranial and trunk neural crest in lampreys may be related to constraints on SoxE
activity among duplicates, but such specialization does not appear to have
occurred in gnathostomes. This highlights an important difference in the
evolution of SoxE activity between these two divergent vertebrate lineages and
provides insights for understanding how cell fate restriction in different NCC
populations may be dependent on subfunctionalization among SoxE duplicates.
PMID- 27502436
TI - Increased avidity for Dpp/BMP2 maintains the proliferation of progenitors-like
cells in the Drosophila eye.
AB - During organ development, the progenitor state is transient, and depends on
specific combinations of transcription factors and extracellular signals. Not
surprisingly, abnormal maintenance of progenitor transcription factors may lead
to tissue overgrowth, and the concurrence of signals from the local environment
is often critical to trigger this overgrowth. Therefore, identifying specific
combinations of transcription factors/signals promoting -or opposing-
proliferation in progenitors is essential to understand normal development and
disease. We have investigated this issue using the Drosophila eye as model.
Transcription factors hth and tsh are transiently expressed in eye progenitors
causing the expansion of the progenitor pool. However, if their co-expression is
maintained experimentally, cell proliferation continues and differentiation is
halted. Here we show that Hth+Tsh-induced tissue overgrowth requires the BMP2 Dpp
and the abnormal hyperactivation of its pathway. Rather than using autocrine Dpp
expression, Hth+Tsh cells increase their avidity for Dpp, produced locally, by
upregulating extracellular matrix components. During normal development, Dpp
represses hth and tsh ensuring that the progenitor state is transient. However,
cells in which Hth+Tsh expression is forcibly maintained use Dpp to enhance their
proliferation.
PMID- 27502437
TI - Quality of life in patients with skin tumors: the mediator role of body image and
social support.
AB - OBJECTIVE: This study analyzed the relationships between illness representations,
psychological morbidity, family stress, and quality of life and whether these
variables were mediated by body image and social support. METHODS: The sample
consisted of 106 patients with skin tumors, who answered the following measures:
Dermatology Life Quality Index, Illness Perception Questionnaire-Brief, Medical
Outcomes Study Social Support Survey, Index of Family Relations, Hospital Anxiety
and Depression Scales, and the Body Image Scale. RESULTS: Patients with poor
quality of life showed more threatening cognitive and emotional illness
representations, less perceived social support, higher psychological morbidity,
and higher concern with body image. Body image mediated the relationship between
cognitive and comprehension illness representations, family stress, psychological
morbidity, and quality of life. Social support mediated the relationship between
family stress/psychological morbidity and quality of life. CONCLUSIONS:
Psychological intervention should focus on body image and social support,
particularly in patients with melanoma, less disease duration, tumors in the
face, head or neck, in an active professional status, and with lower education.
PMID- 27502438
TI - Microfluidic blood plasma separation for medical diagnostics: is it worth it?
AB - Circulating biomarkers are on the verge of becoming powerful diagnostic tools for
various human diseases. However, the complex sample composition makes it
difficult to detect biomarkers directly from blood at the bench or at the point
of-care. Blood cells are often a source of variability of the biomarker signal.
While the interference of hemoglobin is a long known source of variability, the
release of nucleic acids and other cellular components from hemocytes is a new
concern for measurement and detection of circulating extracellular markers.
Research into miniaturised blood plasma separation has been thriving in the last
10 years (2006-2016). Most point-of-care systems need microscale blood plasma
separation, but developed solutions differ in complexity and sample volume range.
But could blood plasma separation be avoided completely? This focused review
weights the advantages and limits of miniaturised blood plasma separation and
highlights the most interesting advances in direct capture as well as smart blood
plasma separation.
PMID- 27502439
TI - Expression patterns of Ikaros family members during positive selection and
lineage commitment of human thymocytes.
AB - The Ikaros family of transcription factors is essential for normal T-cell
development, but their expression pattern in human thymocytes remains poorly
defined. Our goal is to determine how protein levels of Ikaros, Helios and Aiolos
change as human thymocytes progress through the positive selection and lineage
commitment stages. To accomplish this goal, we used multi-parameter flow
cytometry to define the populations in which positive selection and lineage
commitment are most likely to occur. After human thymocytes express CD3 and
receive positive selection signals, the cells down-regulate expression of CD4 to
become transitional single-positive (TSP) CD8+ thymocytes. At this stage, there
was a transient increase in the Ikaros, Helios and Aiolos protein levels. After
the TSP CD8+ developmental stage, some thymocytes re-express CD4 and become CD3hi
double-positive thymocytes before down-regulating CD8 to become mature single
positive CD4+ thymocytes. Except for regulatory T cells, Helios protein levels
declined and Aiolos protein levels transiently increased during CD4+ T-cell
maturation. For thymocytes progressing toward the CD8+ T-cell lineage, TSP CD8+
thymocytes increase their expression of CD3 and maintain high levels of Aiolos
protein as the cells complete their maturation. In summary, we defined the TSP
CD8+ developmental stage in human T-cell development and propose that this stage
is where CD4/CD8 lineage commitment occurs. Ikaros, Helios and Aiolos each
undergo a transient increase in protein levels at the TSP stage before diverging
in their expression patterns at later stages.
PMID- 27502440
TI - Pro-arrhythmogenic effects of CACNA1C G1911R mutation in human ventricular
tachycardia: insights from cardiac multi-scale models.
AB - Mutations in the CACNA1C gene are associated with ventricular tachycardia (VT).
Although the CACNA1C mutations were well identified in patients with cardiac
arrhythmias, mechanisms by which cardiac arrhythmias are generated in such
genetic mutation conditions remain unclear. In this study, we identified a novel
mechanism of VT resulted from enhanced repolarization dispersion which is a key
factor for arrhythmias in the CACNA1C G1911R mutation using multi-scale
computational models of the human ventricle. The increased calcium influx in the
mutation prolonged action potential duration (APD), produced steepened action
potential duration restitution (APDR) curves as well as augmented membrane
potential differences among different cell types during repolarization,
increasing transmural dispersion of repolarization (DOR) and the spatial and
temporal heterogeneity of cardiac electrical activities. Consequentially, the
vulnerability to unidirectional conduction block in response to a premature
stimulus increased at tissue level in the G1911R mutation. The increased
functional repolarization dispersion anchored reentrant excitation waves in
tissue and organ models, facilitating the initiation and maintenance of VT due to
less meandering rotor tip. Thus, the increased repolarization dispersion caused
by the G1911R mutation is a primary factor that may primarily contribute to the
genesis of cardiac arrhythmias in Timothy Syndrome.
PMID- 27502442
TI - Effects of Carbon Content on the Electrochemical Performances of MoS2-C
Nanocomposites for Li-Ion Batteries.
AB - Molybdenum disulfide is popular for rechargeable batteries, especially in Li-ion
batteries, because of its layered structure and relatively high specific
capacity. In this paper, we report MoS2-C nanocomposites that are synthesized by
a hydrothermal process, and their use as anode material for Li-ion batteries.
Ascorbic acid is used as the carbon source, and the carbon contents can be tuned
from 2.5 wt % to 16.2 wt %. With increasing of carbon content, the morphology of
MoS2-C nanocomposites changes from nanoflowers to nanospheres, and the particle
size is decreased from 200 to 60 nm. This change is caused by the chemical
complex interaction of ascorbic acid. The MoS2-C nanocomposite with 8.4 wt % C
features a high capacity of 970 mAh g(-1) and sustains a capacity retention ratio
of nearly 100% after 100 cycles. When the current increases to 1000 mA g(-1), the
capacity still reaches 730 mAh g(-1). The above manifests that the carbon coating
layer does not only accelerate the charge transfer kinetics to supply quick
discharging and charging, but also hold the integrity of the electrode materials
as evidenced by the long cycling stability. Therefore, MoS2-based nanocomposites
could be used as commercial anode materials in Li-ion batteries.
PMID- 27502441
TI - MicroRNA-21 Mediates Angiotensin II-Induced Liver Fibrosis by Activating NLRP3
Inflammasome/IL-1beta Axis via Targeting Smad7 and Spry1.
AB - AIMS: Angiotensin II (AngII), a vasoconstrictive peptide of the renin-angiotensin
system (RAS), promotes hepatic fibrogenesis and induces microRNA-21(mir-21)
expression. Angiotensin-(1-7) [Ang-(1-7)] is a peptide of the RAS, which
attenuates liver fibrosis. Recently, it was reported that the NOD-like receptor
family, pyrin domain containing 3 (NLRP3) inflammasome participated in liver
fibrosis. However, it remains unclear how mir-21 mediates AngII-induced NLRP3
inflammasome activation. We investigate the role of AngII-induced mir-21 in the
regulation of NLRP3 inflammasome/IL-1beta axis in liver fibrosis. RESULTS: In
vivo, circulating mir-21 was upregulated in patients with liver fibrosis and was
positively correlated with liver fibrosis and oxidation. Treatment with Ang-(1-7)
inhibited mir-21, NLRP3 inflammasome, and liver fibrosis after bile duct ligation
(BDL) or AngII infusion. Inhibition of mir-21 suppressed the Smad7/Smad2/3/NOX4,
Spry1/ERK/NF-kappaB pathway, NLRP3 inflammasome, and liver fibrosis induced by
AngII infusion. In vitro, AngII upregulated mir-21 expression via targeting Smad7
and Spry1 in primary hepatic stellate cells (HSCs). In contrast, Ang-(1-7)
suppressed mir-21 expression and oxidation induced by AngII. Overexpression of
mir-21 promoted oxidation, and collagen production enhanced the effect of AngII
on NLRP3 inflammasome activation via the Spry1/ERK/NF-kappaB, Smad7/Smad2/3/NOX4
pathways. However, downregulation of mir-21 exerted the opposite effects.
Innovation and Conclusions: Mir-21 mediates AngII-activated NLRP3 inflammasome
and resultant HSC activation via targeting Spry1 and Smad7. Ang-(1-7) protected
against BDL or AngII infusion-induced hepatic fibrosis and inhibited mir-21
expression. Antioxid. Redox Signal. 27, 1-20.
PMID- 27502443
TI - Tacrolimus induced dermatophyte infection overlying a plaque morphea.
PMID- 27502445
TI - High-efficiency sono-solar-induced degradation of organic dye by the
piezophototronic/photocatalytic coupling effect of FeS/ZnO nanoarrays.
AB - Highly-efficient sono-solar-induced degradation of organic dye by the
piezophototronic/photocatalytic coupling effect of FeS/ZnO nanoarrays was
achieved. A steel screen was used as the substrate for supporting FeS/ZnO
nanoarrays, and the nanoarrays were vertically and uniformly grown on the
substrate via a wet-chemical route. Under ultrasonic and solar irradiation,
FeS/ZnO nanoarrays have high sono-photocatalytic activity for degrading methylene
blue in water. The photogenerated carriers can be separated by a piezoelectric
field and a built-in electric field, resulting in a low recombination rate and
high photocatalytic efficiency. The piezophototronic and photocatalytic effects
were coupled together. The experimental/theoretical data indicate that this novel
wastewater treatment can co-use mechanical and solar energy in nature, and so is
a promising technology for environment improvement.
PMID- 27502444
TI - Breaking through the strength-ductility trade-off dilemma in an Al-Si-based
casting alloy.
AB - Al-Si-based casting alloys have a great potential in various industrial
applications. Common strengthening strategies on these alloys are accompanied
inevitably by sacrifice of ductility, known as strength-ductility trade-off
dilemma. Here, we report a simple route by combining rapid solidification (RS)
with a post-solidification heat treatment (PHT), i.e. a RS + PHT route, to break
through this dilemma using a commercial Al-Si-based casting alloy (A356 alloy) as
an example. It is shown that yield strength and elongation to failure of the RS +
PHT processed alloy are elevated simultaneously by increasing the cooling rate
upon RS, which are not influenced by subsequent T6 heat treatment. Breaking
through the dilemma is attributed to the hierarchical microstructure formed by
the RS + PHT route, i.e. highly dispersed nanoscale Si particles in Al dendrites
and nanoscale Al particles decorated in eutectic Si. Simplicity of the RS + PHT
route makes it being suitable for industrial scaling production. The strategy of
engineering microstructures offers a general pathway in tailoring mechanical
properties of other Al-Si-based alloys. Moreover, the remarkably enhanced
ductility of A356 alloy not only permits strengthening further the material by
work hardening but also enables possibly conventional solid-state forming of the
material, thus extending the applications of such an alloy.
PMID- 27502446
TI - Sultiame revisited: treatment of refractory absence seizures.
AB - Sultiame is recommended for the treatment of benign epilepsy of childhood with
centrotemporal spikes, electrical status epilepticus during slow-wave sleep, as
well as other genetic (idiopathic) focal epilepsies. Sultiame is not
traditionally considered a treatment choice for idiopathic generalised epilepsy,
and it does not appear on the list of drugs recommended for treatment of absence
seizures. We report the efficacy of sultiame in treating three children with drug
resistant absence seizures and discuss the potential use of sultiame beyond the
idiopathic focal epilepsies.
PMID- 27502448
TI - Structural derivation of lipid A from Cronobacter sakazakii using tandem mass
spectrometry.
AB - RATIONALE: Cronobacter sakazakii is a Gram-negative opportunistic pathogen that
can cause necrotizing enterocolitis, bacteremia, and meningitis. Lipid A, the
glycolipid membrane anchor of lipopolysaccharide (LPS), is a potential virulence
factor for C. sakazakii. Given the potential importance of this molecule in
infection and virulence, structural characterization of lipid A was carried out.
METHODS: The structural characterization of lipid A extracted from C. sakazakii
was performed using electrospray ionization and collision-induced dissociation in
a linear ion trap mass spectrometer. Specifically, for detailed structural
characterization, hierarchical tandem mass spectrometry was performed on the
dominant ions present in the precursor ion mass spectra. By comparing the C.
sakazakii fragmentation pathways to those of the known structure of E. coli lipid
A, a structure of C. sakazakii lipid A was derived. RESULTS: The precursor ion at
m/z 1796 from C. sakazakii is produced from a lipid A molecule where the acyl
chains between the 2'b (C14) and 3'b (C12) positions are reversed as compared to
E. coli lipid A. Additionally, the precursor ion at m/z 1824 from C. sakazakii
corresponds to an E. coli structure with the same acyl chain at the 2'b position
(C14), but a longer acyl chain (C14) at the 3'b position versus m/z 1796.
CONCLUSIONS: Two lipid A structures were derived for the C. sakazakii ions at m/z
1796 and 1824. They differed in composition at the 2'b and 3'b acyl chain
substituents, which may be a result of differences in substrate specificity of
the two lipid A acyl chain transferases: LpxL and LpxM. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27502449
TI - Preexisting cognitive impairment in intracerebral hemorrhage.
AB - OBJECTIVES: Preexisting cognitive impairment is a predictor of cognitive decline
after ischemic stroke, but evidence in intracerebral hemorrhage (ICH) is limited.
We aimed to determine the prevalence of premorbid cognitive impairment in
patients with ICH. MATERIALS AND METHODS: We included patients with acute ICH.
Pre-ICH cognitive impairment was determined based on the results of the Informant
Questionnaire on Cognitive Decline in the Elderly (IQCODE) that uses information
from close relatives. Patients were assessed as having been cognitively impaired
with an IQCODE score of >=3.44; an IQCODE >=4.00 indicated pre-ICH dementia. CT
and MRI images were reviewed to determine the extent of white matter lesions and
to measure the radial width of the temporal horn as marker of brain atrophy. We
investigated differences of cardiovascular risk factors and imaging data between
patients with and without pre-ICH cognitive impairment using correlation
analyses, uni- and multivariable regression models. Functional neurological state
was assessed using the modified Rankin Scale (mRS). The mRS was dichotomized at
the level of 3, and a premorbid mRS of 0-2 was considered as functional
independency. RESULTS: Among the 89 participants, median age was 70 years
(interquartile range 58-78) and 52 (58.4%) were male. IQCODE indicated pre-ICH
cognitive impairment in 18.0% (16 of 89), and 83.1% were functionally independent
before ICH. Cognitive impairment was associated with a premorbid mRS>=3 (chi
squared test, P=0.009). In multivariable analysis, prior stroke/transient
ischemic attack (OR 18.29, 95%-CI 1.945-172.033, P=.011) and hematoma volume (OR
0.90, 95%-CI 0.812-0.991, P=.033) were independently associated with pre-ICH
cognitive impairment. CONCLUSIONS: In conclusion, cognitive impairment frequently
precedes ICH. A higher frequency of cerebrovascular events suggests a role of
vascular processes in the development of cognitive impairment before ICH.
PMID- 27502450
TI - Spontaneous Reversion of Mild Cognitive Impairment to Normal Cognition: A
Systematic Review of Literature and Meta-Analysis.
AB - OBJECTIVES: The issue of subjects with mild cognitive impairment (MCI) reverting
to normal cognition (NC) has to date been taken in limited consideration, and no
conclusive data are available on the rate of reversion. We aimed at
systematically reviewing available longitudinal studies on MCI and meta-analyzing
data with the purpose of estimating the proportion of subjects reverting to NC.
DESIGN: We performed a systematic bibliographic search on PubMed, the Cochrane
Library, and the ISI Web of Science databases. We included in the review all
longitudinal studies on MCI published from 1999 up to November 2015. Only studies
with a longitudinal design, a follow-up >=2 years, enrolling subjects with MCI,
and reporting the number or the percentage of subjects reverting to NC were
included. Data extraction was performed independently by 2 authors. The
methodological quality of studies was also assessed by 2 independent authors
using the QUIPS tool. RESULTS: Twenty-five studies were included. The quality of
evidence was found to be moderate. We observed an overall 18% (95% CI 14-22)
reversion rate from MCI to NC. Results from the metaregression showed a
significant association between effect size and study setting. In particular,
estimates significantly varied according to study setting, with an 8% (95% CI 4
11) reversion rate in clinical-based studies and a 25% (95% CI 19-30) rate in
population-based studies. The frequency of reversion from MCI to NC further
increased to 26% when considering only studies of better quality. Only a few
studies were designed to specifically investigate the reversion from MCI to NC,
thus relevant information on this topic was frequently missing. CONCLUSION: Our
data confirm that reversion to normality is a common outcome in subjects with
MCI, thus leading to recommend a more balanced view when approaching the
construct of MCI both in a clinical and in a research setting.
PMID- 27502451
TI - Subclinical Mood and Cognition Impairments and Blood Pressure Control in a Large
Cohort of Elderly Hypertensives.
AB - BACKGROUND: Blood pressure (BP) control in the elderly is often limited by poor
compliance with prescribed regimen. Both can be influenced by clinical cognitive
or mood impairments; however, the impact of subclinical alterations of cognition
or mood remains unknown. OBJECTIVES: To assess the relation between cognition,
mood, and BP control in treated older hypertensive patients. DESIGN: Cross
sectional association study. SETTING: Predefined substudy to the POLFOKUS
nationwide survey investigating the correlates of poor BP control in patients
randomly drawn from primary and specialist practices across Poland. PARTICIPANTS:
1988 outpatients >=65 years of age treated for hypertension for at least 1 year.
MEASUREMENTS: BP was mean of at least 2 office measurements. We assessed
adherence to antihypertensive medications using a questionnaire and performed
screening tests for cognitive deficits [Abbreviated Mental Test Score (AMTS)] and
mood disorders [Geriatric Depression Scale (GDS)]. In all patients, we used a
unified (BP <140/90 mm Hg) and in >=80 years old a unified or age-specific (<150
mm Hg systolic BP) definition of BP control. We fitted logistic regression models
to assess the probability of poor BP control in association with cognitive and
mood disturbances. RESULTS: The mean [standard deviation (SD)] age of 1988 (65.6%
women) patients was 73.9 (6.0) years (19.3% >=80 years old). Cognitive and mood
impairments were observed in 8.0% and 37.2%, respectively. Mean systolic and
diastolic BP were 141.8 (16.4) and 83.6 (9.5) mm Hg, respectively. According to
age-stratified and unified definition of proper BP control, goal BP was achieved
in 65.4% and 38.5% patients >=80 years of age, respectively. In younger patients,
the control reached 46%. Globally, 66% patients adhered to antihypertensive
medications. Poor compliance was related to cognitive and mood impairments. When
unified goal was applied, there was a 15.0% higher risk of finding poor BP
control per 1 score lost in AMTS and an 8.0% increase per 1 score gained in GDS
(all P < .001). CONCLUSION: Poorer BP control is related to subclinical worsening
of cognition and mood, which supports widespread use of the Comprehensive
Geriatric Assessment even in apparently self-dependent older patients with
hypertension.
PMID- 27502452
TI - Ten-year hard and soft tissue results of a pilot double-blinded randomized
controlled trial on immediately loaded post-extractive implants using platform
switching concept.
AB - AIM: To evaluate the 10-year post-loading radiological and esthetic outcomes of
implants inserted in post-extraction sites and restored with or without platform
switching protocol. MATERIAL AND METHODS: Twenty-two patients were scheduled for
maxillary post-extractive implant, using a 13 mm in length and 5.5 mm in diameter
implant (Global, Sweden & Martina, Padua, Italy). They randomly received
definitive restorations using platform-switching concept (abutment 3.8 mm in
diameter: test group) or standard restoration (abutment 5.5 mm in diameter:
control group). Outcome measures were survival rates of implants and prostheses,
peri-implant marginal bone loss and periodontal indices 10 years after prosthetic
loading. Moreover, esthetic parameters including soft tissue buccal peri-implant
mucosal levels (REC) and mesial and distal papilla height (PH) were taken at
definitive restoration, 2 and 10 years thereafter. RESULTS: Nineteen implants
were analyzed after 10 years of follow-up. No implants nor prostheses failed. The
postoperative radiographs demonstrated an overall mean bone loss of 0.18 +/- 0.14
mm in the test group and of 0.80 +/- 0.40 mm in the control group (P = 0.00108).
Test group showed 0.23 +/- 0.51 mm of REC gain and PH was of 0.21 +/- 0.33 mm on
average. On the other side, the control group presented a REC = -0.59 +/- 0.80 mm
with PH = -1.12 +/- 0.55 mm, demonstrating a slight continuous soft tissue
shrinkage during the entire follow-up. The mean values were statistically
significant different between test and control group for both REC gain (P =
0.01174) and PH (P = 0.0009). CONCLUSIONS: With the limitations of this study,
immediate single implant restorations rehabilitated with platform-switching
protocol may provide peri-implant alveolar bone-level stability and avoid
continuous soft tissue shrinkage after 10 years of prosthetic loading compared to
a platform-matching restoration. Further studies involving larger sample sizes
are required to confirm these preliminary results.
PMID- 27502453
TI - Beyond the known functions of the CCR4-NOT complex in gene expression regulatory
mechanisms: New structural insights to unravel CCR4-NOT mRNA processing
machinery.
AB - Large protein assemblies are usually the effectors of major cellular processes.
The intricate cell homeostasis network is divided into numerous interconnected
pathways, each controlled by a set of protein machines. One of these master
regulators is the CCR4-NOT complex, which ultimately controls protein expression
levels. This multisubunit complex assembles around a scaffold platform, which
enables a wide variety of well-studied functions from mRNA synthesis to
transcript decay, as well as other tasks still being identified. Solving the
structure of the entire CCR4-NOT complex will help to define the distribution of
its functions. The recently published three-dimensional reconstruction of the
complex, in combination with the known crystal structures of some of the
components, has begun to address this. Methodological improvements in structural
biology, especially in cryoelectron microscopy, encourage further structural and
protein-protein interaction studies, which will advance our comprehension of the
gene expression machinery.
PMID- 27502454
TI - Plasmonic nanoparticles tuned thermal sensitive photonic polymer for biomimetic
chameleon.
AB - Among many thermo-photochromic materials, the color-changing behavior caused by
temperature and light is usually lack of a full color response. And the study on
visible light-stimuli chromic response is rarely reported. Here, we proposed a
strategy to design a thermo-photochromic chameleon biomimetic material consisting
of photonic poly(N-isopropylacrylamide-co-methacrylic acid) copolymer and
plasmonic nanoparticles which has a vivid color change triggered by temperature
and light like chameleons. We make use of the plasmonic nanoparticles like gold
nanoparticles and silver nanoparticles to increase the sensitivity of the
responsive behavior and control the lower critical solution temperature of the
thermosensitive films by tuning the polymer chain conformation transition.
Finally, it is possible that this film would have colorimetric responses to the
entire VIS spectrum by the addition of different plasmonic nanoparticles to tune
the plasmonic excitation wavelength. As a result, this method provides a
potential use in new biosensors, military and many other aspects.
PMID- 27502455
TI - A self-sufficient system for removal of synthetic dye by coupling of spore
displayed triphenylmethane reductase and glucose 1-dehydrogenase.
AB - Biodegradation of triphenylmethane dyes by microorganisms is hampered by the
transport barrier imposed by cell membranes. On the other hand, cell-free systems
using enzyme-based biodegradation strategy are costly. Therefore, an efficient
and inexpensive approach circumventing these problems is highly desirable. Here,
we constructed a self-sufficient system for synthetic dye removal by coupling of
spore surface-displayed triphenylmethane reductase (TMR) and glucose 1
dehydrogenase (GDH) for the first time. Display of both TMR and GDH significantly
enhanced their stability under conditions of extreme pH and temperature. These
engineered spores also exhibited more robust long-term stability than their
purified counterparts. Furthermore, we observed that a high ratio of spore
displayed GDH is necessary for high dye degradation efficiency. These results
indicate that this continuous dye removal system with cofactor regeneration
offers a promising solution for dye biodegradation applications.
PMID- 27502456
TI - Particle- and gas-phase PAHs toxicity equivalency quantity emitted by a non-road
diesel engine with non-thermal plasma technology.
AB - Polycyclic aromatic hydrocarbon (PAH) toxicity equivalency quantity (TEQ, denoted
by benzo(a)pyrene equivalent (BaPeq) concentration) is more meaningful when
evaluating the influence of non-road diesel engines PAH toxicity on environment.
Particle- and gas-phase PAH BaPeq concentrations were calculated based on gas
chromatography-mass spectrometer (GC-MS) results and toxic equivalency factors. A
non-thermal plasma (NTP) reactor was applied to a non-road diesel engine to
decrease PAH TEQ content. Only the gas-phase Nap BaPeq concentration increased
slightly with the action of NTP at three different generator power outputs. BaP
dominated the BaPeq concentration for 15 samples with, and without NTP except in
the gas-phase at 4 kW. Almost all medium molecular weight (MMW) and high
molecular weight (HMW) PAH TEQs increased for particle- and gas-phases at 3 kW
power output compared to 2 kW without the use of NTP. Particle-phase Nap, Acp,
and AcPy (low molecular weight, LMW) TEQ were under detection at 3 and 4 kW,
while gas-phase BkF, IND, DBA, and BghiP (HMW) concentrations were below the
limits of detection. The most abundant PAH TEQ compounds were MMW and HMW PAHs
for gas- and particle-phase while they were BaA, CHR, BbF, BaP, and IND for PM
aggregation. The total BaPeq emission factors were 15.1, 141.4, and 46.5 MUg m(
3) at three engine loads, respectively. Significant BaPeq concentration
percentage reduction was obtained (more than 80 and 60 %) with the use of NTP for
particle- and gas-phases. A high TEQ content was observed for PM aggregation
(38.8, 98.4, and 50.0 MUg kg(-1)) which may have caused secondary PAH toxicity
emissions. With the action of NTP, the breakup of MMW and HMW into LMW PAHs led
to reduction of some PAH concentrations.
PMID- 27502457
TI - Aseptic hydroponics to assess rhamnolipid-Cd and rhamnolipid-Zn bioavailability
for sunflower (Helianthus annuus): a phytoextraction mechanism study.
AB - The availability of cadmium (Cd) and zinc (Zn) to sunflower (Helianthus annuus)
was investigated in rhamnolipid- and ethylenediaminetetraacetic acid (EDTA)
buffered solutions in order to evaluate the influence of aqueous speciation of
the metals on their uptake by the plant, in relation to predictions of uptake by
the free ion activity model (FIAM). Free metal ion activity was estimated using
the chemical equilibrium program MINTEQ or measured by Donnan dialysis. The
uptake of Cd followed the FIAM for the EDTA-buffered solution at EDTA
concentrations below 0.4 MUM; for the rhamnolipid-buffered solution, the uptake
of both metals in roots was not markedly affected by increasing rhamnolipid
concentrations in solution. This suggests rhamnolipid enhanced metal accumulation
in plant roots (per unit free metal in solution) possibly through formation and
uptake of lipophilic complexes. The addition of normal Ca concentrations (low
millimetre range) to the rhamnolipid uptake solutions reduced Cd accumulation in
shoots by inhibiting Cd translocation, whereas it significantly increased Zn
accumulation in shoots. This study confirms that although rhamnolipid could
enhance accumulation of Cd in plants roots at low Ca supply, it is not suitable
for Cd phytoextraction in contaminated soil environments where Ca concentrations
in soil solution are orders of magnitude greater than those of Cd.
PMID- 27502458
TI - Evaluating the dynamical characteristics of particle matter emissions in an open
ore yard with industrial operation activities.
AB - A study to investigate the dynamical characteristics of particle matter emissions
in a working open yard is conducted in Caofeidian Port of Hebei Province, China.
The average diurnal concentrations of the total suspended particulate (TSP)
matter and respirable particulate matter (PM10 and PM5) are monitored during the
field measurement campaign. Sampling is performed at a regular interval at 8
monitoring stations in the yard with normal industrial activities. The average
TSP, PM10 and PM5 concentrations range from 285 to 568, 198 to 423 and 189 to 330
MUg.m-3 in the yard, respectively. The linear regression correlation coefficient
of TSP/PM10 and TSP/PM5 is 0.95+/-0.01 and 0.88+/-0.02, respectively.By using the
Spearman correlation method, the wind speed and relative humidity are both weakly
correlated with the PM10 and PM5 concentrations according to the measurements. In
addition, industrial operation activities, such as vehicular traffic in the yard
and the loading time of stackers, are significantly positively correlated with
the PM concentration. Using the multivariate regression method, the main
parameters influencing the TSP concentration variations are integratedly
analysed. The traffic volume is found to be a significant predictor of TSP
concentration variation, with the smallest P value (P<0.05).To understand the
dynamical characteristics of particle emissions in the yard, the emissions from
the truck transports, that is, from unpaved haul roads and from the loading
process, are established. Then, the dynamical emission factor (EFD) based on the
industrial activities in the yard is proposed. The dynamical emissions average
5.25x105 kg.year-1 and EFD is evaluated to be 0.29 kg.(ton.day)-1 during the
measurement period. These outcomes have meaningful implications not only for
understanding the dynamical characteristics of particle emissions in the working
stockyard but also for implementing effective control measures at appropriate
sites in the harbour area.
PMID- 27502459
TI - Thermodynamic entropy of organic oxidation in the water environment: experimental
evaluation compared to semi-empirical calculation.
AB - Residual organic matters in the secondary effluent are usually less biodegradable
in terms of the total organic carbon content, and when discharged into a
receiving water body, their further decomposition most likely mainly occurs due
to chemical oxidation. Using this scenario, a semi-empirical method was
previously developed to calculate the thermodynamic entropy of organic oxidation
to quantitatively evaluate the impact of organic discharge on the water
environment. In this study, the relationship between the entropy increase
(DeltaSC) and excess organic mass (DeltaTOC) was experimentally verified via
combustion heat measurement using typical organic chemicals and mixtures. For
individual organic chemicals, a linear relationship was detected between DeltaSC
and DeltaTOC with the same proportionality coefficient, 54.0 kJ/g, determined in
the previous semi-empirical relationship. For the organic mixtures, a linear
relationship was also identified; however, the proportionality coefficient was
69.2 kJ/g, indicating an approximately 28 % increase in the oxidation heat
required to decompose the same organic mass. This increase in energy can likely
be attributed to the synergistic effects of hydrogen bonding, hydrophobic
interactions, pi-pi interactions, and van der Waals interactions between
functional groups of different organic compounds. Intermolecular interactions may
result in 17-32 % more dissociation energy for organic mixtures compared to the
organic components' chemical structures. Because organics discharged into a water
body are always a mixture of organic compounds, the proportionality coefficient
obtained using organic mixtures should be adopted to modify the previously
proposed semi-empirical equation.
PMID- 27502460
TI - Catalytic ozonation of sulfamethoxazole by composite iron-manganese silicate
oxide: cooperation mechanism between adsorption and catalytic reaction.
AB - A systematic investigation of the cooperation mechanism between adsorption and
catalytic reaction during the catalytic ozonation of sulfamethoxazole (SMX) by
composite iron-manganese silicate oxide (FMSO) was carried out in this work.
Results showed that the total organic carbon (TOC) removal increased
significantly from 27 % (sole-ozonation) to 79.8 % (FMSO catalytic ozonation).
The presence of FMSO in the ozonation process effectively enhanced the ozone
utilization efficiency and accelerated the transformation of ozone into hydroxyl
radicals. The latter result was verified by the indirect method, using NaHSO3 as
the reductor, and the direct electron spin resonance (ESR) determination
technology. The adsorption of SMX on FMSO was minimal (1.8 %). However, ozone
rapidly converted SMX into various intermediates, which was exhibited by the much
higher adsorption affinity on the surface of FMSO than that of SMX. The
accumulation of various intermediates on the FMSO surface also increased their
contact probability with the .OH radicals generated by the ozone decomposition.
The continuous interaction of intermediates with .OH radicals could further
promote the benign cycling of the release of adsorption sites and the succeeding
adsorption/decomposition of ozone and intermediates on FMSO. This could be
another reason for the higher and faster TOC removal rate.
PMID- 27502461
TI - The significance of cell-related challenges in the clinical application of tissue
engineering.
AB - Tissue engineering is increasingly being recognized as a new approach that could
alleviate the burden of tissue damage currently managed with transplants or
synthetic devices. Making this novel approach available in the future for
patients who would potentially benefit is largely dependent on understanding and
addressing all those factors that impede the translation of this technology to
the clinic. Cell-associated factors in particular raise many challenges,
including those related to cell sources, up- and downstream techniques,
preservation, and the creation of in vitro microenvironments that enable cells to
grow and function as far as possible as they would in vivo. This article
highlights the main confounding issues associated with cells in tissue
engineering and how these issues may hinder the advancement of therapeutic tissue
engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A:
3157-3163, 2016.
PMID- 27502462
TI - 55-Year-Old Woman With Recurrent Syncope.
PMID- 27502463
TI - Murder Liability for Prescribing Opioids: A Way Forward?
PMID- 27502464
TI - 46-Year-Old Man With Jaundice and Hypoxemia.
PMID- 27502465
TI - Survival predictors in patients with prostate adenocarcinoma with hormonal
blockade.
AB - Ki-67 index and clinical-pathological factors such as the Gleason score and the
presence of neuroendocrine differentiation have been used for predicting survival
in patients with prostate cancer. We examined prostate tissue from 45 patients
with advanced prostate cancer who were treated with maximal androgen blockade and
analysed their cancer-specific survival (CSS). We assessed the Gleason index,
performed an immunohistochemical analysis of Ki-67 (MIB-1) and determined the
presence of neuroendocrine differentiation (chromogranin A). A survival study was
conducted using Kaplan-Meier curves (log-rank test) and a Cox regression
analysis. Twenty-four patients (53.3%) died from the disease, with a mean follow
up of 68.7+/-7.7 months (56.6% CSS at 5 years and 31.8% at 10 years). In the
univariate analysis, survival was associated with an interquartile distribution
of Ki-67 (0-5, 6-12%, 13-25%, >25%; log-rank, p=0.01), Gleason 5 (total index 9
10; log-rank, p=0.002) and the presence of metastases during the diagnosis (M1;
log-rank, p=0.004) but not to cT category (T3-T4; log-rank, p=0.26) or
neuroendocrine differentiation (immunohistochemically positive tumour cell nests;
log-rank, p=0.46). The multivariate analysis revealed that a Ki-67 index <=12%
(HR, 0.22; p=0.0009) and the absence of metastases (M0) during diagnosis (HR,
0.17; p=0.0002) were protective factors in this population. In conclusion, Ki-67
proliferation index and the lack of metastases at diagnosis predict CSS in
patients with advanced prostate cancer who undergo hormonal blockade.
Neuroendocrine differentiation in tumour tissue had no prognostic value in this
study.
PMID- 27502466
TI - Cutaneous syncytial myoepithelioma:: Clinico-pathological features and
differential diagnosis.
AB - Cutaneous syncytial myoepithelioma (CSM) is a very rare tumor belonging to the
spectrum of skin myoepithelial lesions. CSM usually affects the upper extremities
of young to middle aged patients and is characterized by peculiar morphological
and immunohistochemical features. Unlike classic myoepithelioma, CSM is composed
by a densely packed proliferation of spindled to histiocytoid cells, which are
variably positive for EMA, S100, SMA, and frequently negative for cytokeratins
and GFAP. The peculiar histopathology and the extreme rarity of such lesion (less
than 40 cases reported in the literature) can make the diagnosis of CSM a true
challenge. In the present case, we report the clinico-pathological features of a
primary CSM occurring in a 38 year-old Caucasian man. The differential diagnoses
of such lesion are also briefly discussed.
PMID- 27502468
TI - IL-22/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis
with nasal polyps via alteration of MUC1 expression.
AB - BACKGROUND: IL-22 is an IL-10-family cytokine that regulates chronic
inflammation. We investigated the role of IL-22 and its receptor, IL-22R1, in the
pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: IL
22 and IL-22R1 protein and mRNA expression in NP and in uncinate tissues (UT)
from CRS and non-CRS patients was examined using immunohistochemistry and real
time PCR, respectively. Dispersed NP and UT cells were cultured with the
Staphylococcus aureus exotoxins, staphylococcal enterotoxin B and alpha-toxin,
following which exotoxin-induced IL-22 levels and their association with
clinicopathological factors were analyzed. Effects of IL-22 on MUC1 expression
and cytokine release in NP cells were also determined. RESULTS: IL-22 and IL-22R1
in NP were mainly expressed in infiltrating inflammatory cells and in epithelial
cells, respectively. IL-22 mRNA levels in NP were significantly higher than those
in UTs from non-CRS patients whereas IL-22R1 levels were conversely lower in NPs.
NP cells produced substantial amounts of IL-22 in response to exotoxins. Exotoxin
induced IL-22 production by NP cells significantly and negatively correlated with
the degree of local eosinophilia and postoperative computed tomography (CT)
score, whereas conversely it positively correlated with the forced expiratory
volume in 1s (FEV1)/forced vital capacity (FVC) ratio. IL-22 significantly
enhanced MUC1 mRNA expression in NP cells. IL-22-induced MUC1 mRNA levels were
significantly and positively correlated with IL-22R1 mRNA levels in NPs.
CONCLUSIONS: These data suggest that imbalance of IL-22/IL-22R1 signaling
regulates the pathogenesis of CRSwNP, including local eosinophilia, via
alteration of MUC1 expression.
PMID- 27502469
TI - Validation of an algorithm to predict reulceration in amputation patients with
diabetes.
AB - The aim of this article was to assess the ability to predict reulceration in
people with diabetes and a history of minor amputation according to the formula
proposed by Miller et al. A retrospective study was performed on 156 consecutive
records of patients with a recent history of simple or multiple forefoot
amputation. The sample was divided according to Miller's formula into patients at
low risk of reulceration and those at high risk; those were further divided into
two subgroups according to whether or not the first segment of the forefoot had
been amputated. Forty-eight (47.1%) individuals suffered forefoot reulceration,
showing a median reulceration-free survival time of 8 months [interquartile range
(IR) 3.6-14.8]. Nephropathy (P = 0.005) and Miller's formula (P = 0.028) were
risk factors for reulceration-free survival time in the univariate analysis. The
pattern relating to the first segment amputated [hazard ratio (HR) 2.853; P =
0.004; 95% confidence interval (CI) 1.391-5.849] and nephropathy (HR 2.468; P =
0.004; 95% CI 1.328-4.587) showed a significant hazard ratio in the multivariate
Cox model. Participants with first segment amputation and one other amputation
showed an association with the probability of reulceration in comparison with any
other specific type of minor amputation.
PMID- 27502470
TI - The relative contributions of store-operated and voltage-gated Ca2+ channels to
the control of Ca2+ oscillations in airway smooth muscle.
AB - KEY POINTS: Agonist-dependent oscillations in the concentration of free cytosolic
calcium are a vital mechanism for the control of airway smooth muscle contraction
and thus are a critical factor in airway hyper-responsiveness. Using a
mathematical model, closely tied to experimental work, we show that the
oscillations in membrane potential accompanying the calcium oscillations have no
significant effect on the properties of the calcium oscillations. In addition,
the model shows that calcium entry through store-operated calcium channels is
critical for calcium oscillations, but calcium entry through voltage-gated
channels has much less effect. The model predicts that voltage-gated channels are
less important than store-operated channels in the control of airway smooth
muscle tone. ABSTRACT: Airway smooth muscle contraction is typically the key
mechanism underlying airway hyper-responsiveness, and the strength of muscle
contraction is determined by the frequency of oscillations of intracellular
calcium (Ca2+ ) concentration. In airway smooth muscle cells, these Ca2+
oscillations are caused by cyclic Ca2+ release from the sarcoplasmic reticulum,
although Ca2+ influx via plasma membrane channels is also necessary to sustain
the oscillations over longer times. To assess the relative contributions of store
operated and voltage-gated Ca2+ channels to this Ca2+ influx, we generated a
comprehensive mathematical model, based on experimental Ca2+ measurements in
mouse precision-cut lung slices, to simulate Ca2+ oscillations and changes in
membrane potential. Agonist-induced Ca2+ oscillations are accompanied by
oscillations in membrane potential, although the membrane potential oscillations
are too small to generate large Ca2+ currents through voltage-gated Ca2+
channels, and thus have little effect on the Ca2+ oscillations. Ca2+ entry
through voltage-gated channels only becomes important when the cell is
depolarized (e.g. by a high external K+ concentration). As a result, agonist
induced Ca2+ oscillations are critically dependent on Ca2+ entry through store
operated channels but do not depend strongly on Ca2+ entry though voltage-gated
channels.
PMID- 27502471
TI - PARL: The mitochondrial rhomboid protease.
AB - The rhomboid family comprises evolutionary conserved intramembrane proteases
involved in a wide spectrum of biologically relevant activities. A mitochondrion
localized rhomboid, called PARL in mammals, and conserved in yeast and Drosophila
as RBD1/PCP1 and rho-7, respectively, plays an indispensable role in cell
homeostasis as illustrated by the severe phenotypes caused by its genetic
ablation in the various investigated species. Although several substrates of PARL
have been proposed to explain these phenotypes, there remains a lot of
controversy in this important area of research. We review here the putative
functions and substrates of PARL and its orthologues in different species,
highlighting areas of uncertainty, and discuss its potential involvement in some
prevalent diseases such as type II diabetes and Parkinson's disease.
PMID- 27502472
TI - Attention-deficit hyperactivity disorder in adults: a systematic review and meta
analysis of genetic, pharmacogenetic and biochemical studies.
PMID- 27502473
TI - All naturally occurring autoantibodies against the NMDA receptor subunit NR1 have
pathogenic potential irrespective of epitope and immunoglobulin class.
AB - Autoantibodies of the IgG class against N-methyl-d-aspartate-receptor subunit NR1
(NMDAR1) were first described in anti-NMDAR encephalitis and seen as disease
indicators. Recent work on together over 5000 individuals challenged this
exclusive view by showing age-dependently up to >20% NMDAR1-autoantibody
seroprevalence with comparable immunoglobulin class and titer distribution across
health and disease. The key question therefore is to understand the properties of
these autoantibodies, also in healthy carriers, in order to assess secondary
complications and possible contributions to neuropsychiatric disease. Here, we
believe we provide for human NMDAR1-autoantibodies the first comprehensive
analysis of their target epitopes and functionality. We selected sera of
representative carriers, healthy or diagnosed with very diverse conditions, that
is, schizophrenia, age-related disorders like hypertension and diabetes, or anti
NMDAR encephalitis. We show that all positive sera investigated, regardless of
source (ill or healthy donor) and immunoglobulin class, provoked NMDAR1
internalization in human-induced pluripotent stem cell-derived neurons and
reduction of glutamate-evoked currents in NR1-1b/NR2A-expressing Xenopus oocytes.
They displayed frequently polyclonal/polyspecific epitope recognition in the
extracellular or intracellular NMDAR1 domains and some additionally in NR2A. We
conclude that all circulating NMDAR1-autoantibodies have pathogenic potential
regarding the whole spectrum of neuronal NMDAR-mediated effects upon access to
the brain in situations of increased blood-brain-barrier permeability.
PMID- 27502474
TI - Genome-wide common and rare variant analysis provides novel insights into
clozapine-associated neutropenia.
AB - This corrects the article DOI: 10.1038/mp.2016.97.
PMID- 27502476
TI - Exome-sequencing in a large population-based study reveals a rare Asn396Ser
variant in the LIPG gene associated with depressive symptoms.
PMID- 27502477
TI - Towards natural language question generation for the validation of ontologies and
mappings.
AB - BACKGROUND: The increasing number of open-access ontologies and their key role in
several applications such as decision-support systems highlight the importance of
their validation. Human expertise is crucial for the validation of ontologies
from a domain point-of-view. However, the growing number of ontologies and their
fast evolution over time make manual validation challenging. METHODS: We propose
a novel semi-automatic approach based on the generation of natural language (NL)
questions to support the validation of ontologies and their evolution. The
proposed approach includes the automatic generation, factorization and ordering
of NL questions from medical ontologies. The final validation and correction is
performed by submitting these questions to domain experts and automatically
analyzing their feedback. We also propose a second approach for the validation of
mappings impacted by ontology changes. The method exploits the context of the
changes to propose correction alternatives presented as Multiple Choice
Questions. RESULTS: This research provides a question optimization strategy to
maximize the validation of ontology entities with a reduced number of questions.
We evaluate our approach for the validation of three medical ontologies. We also
evaluate the feasibility and efficiency of our mappings validation approach in
the context of ontology evolution. These experiments are performed with different
versions of SNOMED-CT and ICD9. CONCLUSIONS: The obtained experimental results
suggest the feasibility and adequacy of our approach to support the validation of
interconnected and evolving ontologies. Results also suggest that taking into
account RDFS and OWL entailment helps reducing the number of questions and
validation time. The application of our approach to validate mapping evolution
also shows the difficulty of adapting mapping evolution over time and highlights
the importance of semi-automatic validation.
PMID- 27502475
TI - mGluR2/3 mechanisms in primate dorsolateral prefrontal cortex: evidence for both
presynaptic and postsynaptic actions.
AB - Cognitive deficits in psychiatric and age-related disorders generally involve
dysfunction of the dorsolateral prefrontal cortex (dlPFC), but there are few
treatments for these debilitating symptoms. Group II metabotropic glutamate
receptors (mGluR2/3), which couple to Gi/Go, have been a focus of therapeutics
based on rodent research, where mGluR2/3 have been shown to reduce axonal
glutamate release and increase glial glutamate uptake. However, this strategy has
had mixed results in patients, and understanding mGluR2/3 mechanisms in primates
will help guide therapeutic interventions. The current study examined mGluR2/3
localization and actions in the primate dlPFC layer III circuits underlying
working memory, where the persistent firing of 'Delay cells' is mediated by N
methyl-d-aspartate receptors and weakened by cAMP-PKA-potassium channel signaling
in dendritic spines. Immunoelectron microscopy identified postsynaptic mGluR2/3
in the spines, in addition to the traditional presynaptic and astrocytic
locations. In vivo iontophoretic application of the mGluR2/3 agonists (2R, 4R)
APDC or LY379268 onto dlPFC Delay cells produced an inverted-U effect on working
memory representation, with enhanced neuronal firing following low doses of
mGluR2/3 agonists. The enhancing effects were reversed by an mGluR2/3 antagonist
or by activating cAMP signaling, consistent with mGluR2/3 inhibiting postsynaptic
cAMP signaling in spines. Systemic administration of these agonists to monkeys
performing a working memory task also produced an inverted-U dose-response, where
low doses improved performance but higher doses, similar to clinical trials, had
mixed effects. Our data suggest that low doses of mGluR2/3 stimulation may have
therapeutic effects through unexpected postsynaptic actions in dlPFC,
strengthening synaptic connections and improving cognitive function.
PMID- 27502478
TI - Precursors of age-related macular degeneration: associations with vitamin A and
interaction with CFHY402H in the Inter99 Eye Study.
AB - PURPOSE: To investigate associations of very early age-related macular
degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E,
vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in
complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross-sectional
study of 848 subjects aged 30-60 years from the Inter99 Eye Study. Daily intake
of vitamins and minerals was estimated from a 198-item food frequency
questionnaire. Digital fundus photographs were recorded in red-free illumination
and graded for macular drusen >63 MUm and numerous (>20) small hard macular
drusen as a mean of both eyes. RESULTS: Higher intake of vitamin A increased the
risk of having macular drusen >63 MUm with odds ratio = 1.82 (CI95 1.02-3.24, p =
0.042) comparing participants in the highest quartile of vitamin A intake with
participants in the lowest quartile, adjusted for recruitment group, age and sex.
There was a significant interaction with CFHY402H (p = 0.038). Among 504
participants with CFHY402H, the relative risk of having macular drusen >63 MUm
was increased in participants in the highest quartile of vitamin A intake (odds
ratio = 2.58; CI95 1.16-5.73, p = 0.020) and in the second highest quartile (odds
ratio = 3.27; CI95 1.50-7.13, p = 0.0029) compared with the lowest quartile.
Further adjusting for total fat intake, energy intake, plasma cholesterol, body
mass index (BMI), smoking, alcohol intake, education and physical activity
strengthened the association. CONCLUSIONS: In this cross-sectional study, a
higher intake of vitamin A increased the risk of macular drusen >63 MUm in
subjects with CFHY402H. The study supports that vitamin A may be a risk factor
for early AMD.
PMID- 27502479
TI - A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac
Myocytes and Nonmyocytes From the Adult Mouse Heart.
AB - RATIONALE: Cardiovascular disease represents a global pandemic. The advent of and
recent advances in mouse genomics, epigenomics, and transgenics offer ever
greater potential for powerful avenues of research. However, progress is often
constrained by unique complexities associated with the isolation of viable
myocytes from the adult mouse heart. Current protocols rely on retrograde aortic
perfusion using specialized Langendorff apparatus, which poses considerable
logistical and technical barriers to researchers and demands extensive training
investment. OBJECTIVE: To identify and optimize a convenient, alternative
approach, allowing the robust isolation and culture of adult mouse cardiac
myocytes using only common surgical and laboratory equipment. METHODS AND
RESULTS: Cardiac myocytes were isolated with yields comparable to those in
published Langendorff-based methods, using direct needle perfusion of the LV ex
vivo and without requirement for heparin injection. Isolated myocytes can be
cultured antibiotic free, with retained organized contractile and mitochondrial
morphology, transcriptional signatures, calcium handling, responses to hypoxia,
neurohormonal stimulation, and electric pacing, and are amenable to patch clamp
and adenoviral gene transfer techniques. Furthermore, the methodology permits
concurrent isolation, separation, and coculture of myocyte and nonmyocyte cardiac
populations. CONCLUSIONS: We present a novel, simplified method, demonstrating
concomitant isolation of viable cardiac myocytes and nonmyocytes from the same
adult mouse heart. We anticipate that this new approach will expand and
accelerate innovative research in the field of cardiac biology.
PMID- 27502480
TI - A school-based health promotion programme to increase help-seeking for substance
use and mental health problems: study protocol for a randomised controlled trial.
AB - BACKGROUND: Adolescence is a high-risk time for the development of mental health
and substance use problems. However, fewer than one in four 16-24 year-olds with
a current disorder access health services, with those experiencing a substance
use disorder being the least likely to seek professional help. Research indicates
that young people are keeping their problems to themselves or alternatively,
turning to peers or trusted adults in their lives for help. These help-seeking
preferences highlight the need to build the mental health literacy of
adolescents, to ensure that they know when and how to assist themselves and their
peers to access support. The MAKINGtheLINK intervention aims to introduce these
skills to adolescents within a classroom environment. METHODS/DESIGN: This is a
cluster randomised controlled trial (RCT) with schools as clusters and individual
students as participants from 22 secondary schools in Victoria, Australia.
Schools will be randomly assigned to either the MAKINGtheLINK intervention group
or the waitlist control group. All students will complete a self-report
questionnaire at baseline, immediately post intervention and 6 and 12 months post
baseline. The primary outcome to be assessed is increased help-seeking behaviour
(from both formal and informal sources) for alcohol and mental health issues,
measured at 12 months post baseline. DISCUSSION: The findings from this research
will provide evidence on the effectiveness of the MAKINGtheLINK intervention for
teaching school students how to overcome prominent barriers associated with
seeking help, as well as how to effectively support their peers. If deemed
effective, the MAKINGtheLINK programme will be the first evidence-informed
resource that is able to address critical gaps in the knowledge and behaviour of
adolescents in relation to help-seeking. It could, therefore, be a valuable
resource that could be readily implemented by classroom teachers. TRIAL
REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR):
ACTRN12613000235707 . Registered on 27 February 2013.
PMID- 27502481
TI - Sox2: A multitasking networker.
AB - The transcription factor Sox2 is best known as a pluripotency factor in stem and
precursor cells and its expression generally correlates with an undifferentiated
state. Proposed modes of action include those as classical transcription factor
and pre-patterning factor with influence on histone modifications and chromatin
structure. Recently, we provided the first detailed analysis of Sox2 expression
and function during development of oligodendrocytes, the myelin-forming cells of
the CNS. Surprisingly, we found evidence for a role of Sox2 as differentiation
factor and found it to act through modulation of microRNA levels. Thus, we add
new facets to the functional repertoire of Sox2 and throw light on the networking
activity of this multitasking developmental regulator.
PMID- 27502482
TI - A case of lymphomatosis cerebri mimicking inflammatory diseases.
AB - BACKGROUND: Lymphomatosis cerebri (LC) is a rare subtype of primary central
nervous system malignant lymphoma. The typical features of this disease exhibited
on magnetic resonance imaging (MRI) without contrast enhancement are similar to
those observed with diffuse leukoencephalopathy, mimicking white matter disorders
such as encephalitis. Clinical features and examination findings that are
suggestive of inflammatory diseases may indeed confound the diagnosis of LC. CASE
PRESENTATION: A 66-year-old woman with continuous fever over a two-month period
developed left hemiparesis despite presenting in an alert state with normal
cognitive function. Sampling tests showed autoantibodies in the serum and
inflammatory changes in the cerebrospinal fluid. The results from an MRI
demonstrated multiple non-enhanced brain lesions in the splenium of the corpus
callosum and deep white matter. Single photon emission computed tomography
revealed increases in blood flow in the basal ganglia, thalamus and brainstem. No
systemic malignancies were found. The patient was suspected of having a diagnosis
of nonvasculitic autoimmune inflammatory meningoencephalitis and treated with
intravenous methylprednisolone pulse therapy. Her fever transiently dropped to
within the normal range. However, she had a sudden seizure and a second MRI
exhibited infiltrative lesions gradually extending throughout the whole brain. We
performed a brain biopsy, and LC was histologically diagnosed. The patient
received whole-brain radiation therapy, which diminished the fever and seizures.
The patient died one year after the initial onset of fever. CONCLUSIONS: The
present case yields an important consideration that brain neoplasms, especially
LC, cannot be ruled out, even in cases with clinical characteristics and
examinations consistent with inflammatory diseases. Careful follow-up and
histological study are vital for the correct diagnosis of LC.
PMID- 27502483
TI - RECQ5 helicase promotes resolution of conflicts between replication and
transcription in human cells.
AB - Collisions between replication and transcription machineries represent a
significant source of genomic instability. RECQ5 DNA helicase binds to RNA
polymerase (RNAP) II during transcription elongation and suppresses transcription
associated genomic instability. Here, we show that RECQ5 also associates with
RNAPI and enforces the stability of ribosomal DNA arrays. We demonstrate that
RECQ5 associates with transcription complexes in DNA replication foci and
counteracts replication fork stalling in RNAPI- and RNAPII-transcribed genes,
suggesting that RECQ5 exerts its genome-stabilizing effect by acting at sites of
replication-transcription collisions. Moreover, RECQ5-deficient cells accumulate
RAD18 foci and BRCA1-dependent RAD51 foci that are both formed at sites of
interference between replication and transcription and likely represent
unresolved replication intermediates. Finally, we provide evidence for a novel
mechanism of resolution of replication-transcription collisions wherein the
interaction between RECQ5 and proliferating cell nuclear antigen (PCNA) promotes
RAD18-dependent PCNA ubiquitination and the helicase activity of RECQ5 promotes
the processing of replication intermediates.
PMID- 27502484
TI - TMX1 determines cancer cell metabolism as a thiol-based modulator of ER
mitochondria Ca2+ flux.
AB - The flux of Ca(2+) from the endoplasmic reticulum (ER) to mitochondria regulates
mitochondria metabolism. Within tumor tissue, mitochondria metabolism is
frequently repressed, leading to chemotherapy resistance and increased growth of
the tumor mass. Therefore, altered ER-mitochondria Ca(2+) flux could be a cancer
hallmark, but only a few regulatory proteins of this mechanism are currently
known. One candidate is the redox-sensitive oxidoreductase TMX1 that is enriched
on the mitochondria-associated membrane (MAM), the site of ER-mitochondria Ca(2+)
flux. Our findings demonstrate that cancer cells with low TMX1 exhibit increased
ER Ca(2+), accelerated cytosolic Ca(2+) clearance, and reduced Ca(2+) transfer to
mitochondria. Thus, low levels of TMX1 reduce ER-mitochondria contacts, shift
bioenergetics away from mitochondria, and accelerate tumor growth. For its role
in intracellular ER-mitochondria Ca(2+) flux, TMX1 requires its thioredoxin motif
and palmitoylation to target to the MAM. As a thiol-based tumor suppressor, TMX1
increases mitochondrial ATP production and apoptosis progression.
PMID- 27502485
TI - A disulfide bond in the TIM23 complex is crucial for voltage gating and
mitochondrial protein import.
AB - Tim17 is a central, membrane-embedded subunit of the mitochondrial protein import
machinery. In this study, we show that Tim17 contains a pair of highly conserved
cysteine residues that form a structural disulfide bond exposed to the
intermembrane space (IMS). This disulfide bond is critical for efficient protein
translocation through the TIM23 complex and for dynamic gating of its preprotein
conducting channel. The disulfide bond in Tim17 is formed during insertion of the
protein into the inner membrane. Whereas the import of Tim17 depends on the
binding to the IMS protein Mia40, the oxidoreductase activity of Mia40 is
surprisingly dispensable for Tim17 oxidation. Our observations suggest that Tim17
can be directly oxidized by the sulfhydryl oxidase Erv1. Thus, import and
oxidation of Tim17 are mediated by the mitochondrial disulfide relay, though the
mechanism by which the disulfide bond in Tim17 is formed differs considerably
from that of soluble IMS proteins.
PMID- 27502486
TI - A Toll receptor-FoxO pathway represses Pavarotti/MKLP1 to promote microtubule
dynamics in motoneurons.
AB - FoxO proteins are evolutionarily conserved regulators of neuronal structure and
function, yet the neuron-specific pathways within which they act are poorly
understood. To elucidate neuronal FoxO function in Drosophila melanogaster, we
first screened for FoxO's upstream regulators and downstream effectors. On the
upstream side, we present genetic and molecular pathway analyses indicating that
the Toll-6 receptor, the Toll/interleukin-1 receptor domain adaptor dSARM, and
FoxO function in a linear pathway. On the downstream side, we find that Toll-6
FoxO signaling represses the mitotic kinesin Pavarotti/MKLP1 (Pav-KLP), which
itself attenuates microtubule (MT) dynamics. We next probed in vivo functions for
this novel pathway and found that it is essential for axon transport and
structural plasticity in motoneurons. We demonstrate that elevated expression of
Pav-KLP underlies transport and plasticity phenotypes in pathway mutants,
indicating that Toll-6-FoxO signaling promotes MT dynamics by limiting Pav-KLP
expression. In addition to uncovering a novel molecular pathway, our work reveals
an unexpected function for dynamic MTs in enabling rapid activity-dependent
structural plasticity.
PMID- 27502487
TI - ERK signaling promotes cell motility by inducing the localization of myosin 1E to
lamellipodial tips.
AB - Signaling by extracellular signal-regulated kinase (ERK) plays an essential role
in the induction of cell motility, but the precise mechanism underlying such
regulation has remained elusive. We recently identified SH3P2 as a negative
regulator of cell motility whose function is inhibited by p90 ribosomal S6 kinase
(RSK)-mediated phosphorylation downstream of ERK. We here show that myosin 1E
(Myo1E) is a binding partner of SH3P2 and that the interaction of the two
proteins in the cytosol prevents the localization of Myo1E to the plasma
membrane. Serum-induced phosphorylation of SH3P2 at Ser(202) by RSK results in
dissociation of Myo1E from SH3P2 in the cytosol and the subsequent localization
of Myo1E to the tips of lamellipodia mediated by binding of its TH2 domain to F
actin. This translocation of Myo1E is essential for lamellipodium extension and
consequent cell migration. The ERK signaling pathway thus promotes cell motility
through regulation of the subcellular localization of Myo1E.
PMID- 27502488
TI - Mitochondrial protein import: An unexpected disulfide bond.
AB - Most mitochondrial proteins are imported through the TIM23 translocation channel,
the structure and molecular nature of which are still unclear. In this issue,
Ramesh et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602074) show
that the TIM23 subunit Tim17 contains a disulfide bond that is crucial for
protein translocation and channel gating.
PMID- 27502489
TI - VPS35 binds farnesylated N-Ras in the cytosol to regulate N-Ras trafficking.
AB - Ras guanosine triphosphatases (GTPases) regulate signaling pathways only when
associated with cellular membranes through their C-terminal prenylated regions.
Ras proteins move between membrane compartments in part via diffusion-limited,
fluid phase transfer through the cytosol, suggesting that chaperones sequester
the polyisoprene lipid from the aqueous environment. In this study, we analyze
the nature of the pool of endogenous Ras proteins found in the cytosol. The
majority of the pool consists of farnesylated, but not palmitoylated, N-Ras that
is associated with a high molecular weight (HMW) complex. Affinity purification
and mass spectrographic identification revealed that among the proteins found in
the HMW fraction is VPS35, a latent cytosolic component of the retromer coat.
VPS35 bound to N-Ras in a farnesyl-dependent, but neither palmitoyl- nor
guanosine triphosphate (GTP)-dependent, fashion. Silencing VPS35 increased N
Ras's association with cytoplasmic vesicles, diminished GTP loading of Ras, and
inhibited mitogen-activated protein kinase signaling and growth of N-Ras
dependent melanoma cells.
PMID- 27502490
TI - Systemically and cutaneously distributed ectoparasiticides: a review of the
efficacy against ticks and fleas on dogs.
AB - Acaricidal (tick) and insecticidal (flea) efficacy of systemically and
cutaneously distributed ectoparasiticide products for dogs are compared based on
permethrin and fluralaner as representative molecules. Results of efficacy
studies against fleas and ticks are reviewed that show generally good to
excellent results. Both externally and systemically distributed treatments have
benefits and weaknesses in potentially preventing pathogen transmission by these
arthropod vectors.Four general properties are considered related to the goal of
providing optimal reduction in the risk of vector-borne pathogen transmission.
These are: 1. Owner adherence to the recommended treatment protocol; 2. Rapid
onset of activity following administration; 3. Uniform efficacy over all areas of
the treated dog at risk for parasite attachment; 4. Maintenance of high efficacy
throughout the retreatment interval. In considering these four factors, a
systemically distributed acaricide can offer an option that is at least as
effective as a cutaneously administered acaricide with regard to the overall goal
of reducing the risk of vector-borne pathogen transmission.
PMID- 27502491
TI - Factors associated with needle sharing among people who inject drugs in Yunnan,
China: a combined network and regression analysis.
AB - BACKGROUND: Network analyses have been widely utilized to evaluate large
datasets, but have not yet been used to explore factors associated with risk
behaviours. In combination with traditional regression analysis, network analyses
may provide useful information and highlight key factors for reducing needle
sharing behaviours among people who inject drugs (PWID). METHODS:
Sociodemographic data, and information on injection behaviour and sexual
practices were collected from a cross-sectional survey that was conducted with
PWID in five prefectures of Yunnan province, China. A combination of logistic
regression and correlation network analyses were used to explore key factors for
reducing needle-sharing behaviours among PWID. RESULTS: In a total of 1 049 PWID,
37.5 % had a history of needle or syringe sharing. The logistic analysis showed
that Zhaotong, Qujing, Dehong, or Lincang residents, diazepam use, longer
injection duration, needle reuse, and infection with HIV, viral hepatitis,
tuberculosis and/or malaria were independently associated with needle sharing.
The correlation network analyses showed that, compared to PWID who had never
shared needles, PWID who did share needles would achieve harm reduction goals
faster and more permanently. HIV serostatus and marital status were found to be
closely associated with other risk factors. By combining regression analyses with
network analyses, it was shown that PWID who are HIV seropositive will be an
ideal target group for harm reduction programs. CONCLUSION: Needle-sharing
behaviours are common among PWID in Yunnan, and harm reduction programs may help
PWID who are HIV seropositive reduce risk behaviours and prevent blood borne
diseases.
PMID- 27502492
TI - Antiangiogenic and antihepatocellular carcinoma activities of the Juniperus
chinensis extract.
AB - BACKGROUND: To identify a novel therapeutic agent for hepatocellular carcinoma
(HCC), for which no promising therapeutic agent exists, we screened a panel of
plants and found that Juniperus chinensis exhibited potential antiangiogenic and
anti-HCC activities. We further investigated the antiangiogenic and anti-HCC
effects of the active ingredient of J. chinensis extract, CBT-143-S-F6F7, both in
vitro and in vivo. METHODS: A tube formation assay conducted using human
umbilical vein endothelial cells (HUVECs) was first performed to identify the
active ingredient of CBT-143-S-F6F7. A series of angiogenesis studies, including
HUVEC migration, Matrigel plug, and chorioallantoic membrane (CAM) assays, were
then performed to confirm the effects of CBT-143-S-F6F7 on angiogenesis. The
effects of CBT-143-S-F6F7 on tumor growth were investigated using a subcutaneous
and orthotopic mouse model of HCC. In vitro studies were performed to investigate
the effects of CBT-143-S-F6F7 on the cell cycle and apoptosis in HCC cells.
Moreover, protein arrays for angiogenesis and apoptosis were used to discover
biomarkers that may be influenced by CBT-143-S-F6F7. Finally, nuclear magnetic
resonance analysis was conducted to identify the compounds of CBT-143-S-F6F7.
RESULTS: CBT-143-S-F6F7 showed significantly antiangiogenic activity in various
assays, including HUVEC tube formation and migration, CAM, and Matrigel plug
assays. In in vivo studies, gavage with CBT-143-S-F6F7 significantly repressed
subcutaneous Huh7 tumor growth in severe combined immunodeficient (SCID) mice,
and prolonged the survival of orthotopic Huh7 tumor-bearing SCID mice (a 40 %
increase in median survival duration compared with the vehicle-treated mice).
Immunohistochemical staining of subcutaneous Huh7 tumors in CBT-143-S-F6F7
treated mice showed a significantly decrease in the cell cycle regulatory protein
cyclin D1, cellular proliferation marker Ki-67, and endothelial marker CD31. CBT
143-S-F6F7 caused arrest of the G2/M phase and induced Huh7 cell apoptosis,
possibly contributing to the inhibition of HCC tumors. Protein array analysis
revealed that several angiogenic and antiapoptotic factors were suppressed in CBT
143-S-F6F7-treated Huh7 cells. Finally, five compounds from CBT-143-S-F6F7 were
identified. CONCLUSIONS: According to these results, we report for the first time
the antiangiogenic and anti-HCC activities of CBT-143-S-F6F7, the active
fractional extract of J. chinensis. We believe that CBT-143-S-F6F7 warrants
further evaluation as a new anti-HCC drug.
PMID- 27502493
TI - Evaluation of long-term surgical site occurrences in ventral hernia repair:
implications of preoperative site independent MRSA infection.
AB - PURPOSE: Previous work demonstrated that prior MRSA infection [MRSA(+)] is
associated with 30-day surgical site infection (SSI) following ventral hernia
repair (VHR). We aimed to determine the impact of MRSA(+) on long-term wound
outcomes after VHR. PARTICIPANTS: A retrospective cohort study was performed at a
tertiary center between July 11, 2005, and May 18, 2012, of patients undergoing
elective VHR with class I wounds. Patients with documented preoperative MRSA
infection at any site (urinary, bloodstream, SSI, etc.) were considered MRSA(+).
Primary outcome was 2-year surgical site occurrence (SSO), defined as SSI,
cellulitis, necrosis, nonhealing wound, seroma, hematoma, dehiscence, or fistula.
SSOs were subdivided into those that required procedural intervention (SSOPI) and
those that did not. RESULTS: Among 632 patients, 46 % were female with average
age 53 +/- 13 years. There were 368 SSOs in 193 patients (31 %); an SSOPI
occurred in 9.8 % (n = 62). The most common SSOs were cellulitis (91/632), seroma
(91/632), and serous drainage (58/632). The rate of 2-year SSO was higher with
MRSA(+) compared to those without (46 vs. 29 %, p = 0.023), attributed to
increased soft tissue necrosis, purulent drainage, serous drainage, cellulitis,
and fistula. In multivariable analysis, MRSA(+) was not associated with 2-year
SSO (HR 1.5, 95 % CI 0.91-2.55, p = 0.113); factors associated with SSO included
obesity, immunosuppression, mesh repair, and operative times. CONCLUSIONS: This
study is the first to evaluate long-term SSOs and SSOPIs after VHR, highlighting
the importance of long-term follow-up. Though not independently associated with
SSOs, MRSA(+) may be a marker of hernia complexity.
PMID- 27502494
TI - Changes in posterior corneal elevations after combined transepithelial
photorefractive keratectomy and accelerated corneal collagen cross-linking:
retrospective, comparative observational case series.
AB - BACKGROUND: To compare the changes in anterior and posterior corneal elevations
after combined transepithelial photorefractive keratectomy (PRK) and accelerated
corneal collagen cross-linking (CXL) and after PRK. METHODS: Medical records of
82 eyes of 44 patients undergoing either combined transepithelial PRK and CXL
(PRK-CXL group) or transepithelial PRK (PRK group) were examined retrospectively.
Changes in anterior and posterior corneal elevations were calculated by fitting
an 8.0-mm diameter best-fit sphere and best-fit toric ellipsoid (BFTE) to the
corneal shape with a fixed eccentricity of 0.4 using Scheimpflug tomography
(Pentacam HR; Oculus Optikgerate GmbH, Wetzlar, Germany) preoperatively and 6
months postoperatively. RESULTS: In anterior corneal elevation, both groups
demonstrated a similar trend of a forward displacement of peripheral anterior
corneal surface and a backward displacement of central anterior corneal surface.
In posterior corneal elevation, a forward displacement of peripheral posterior
corneal surface was induced in both groups, along with a backward displacement of
central posterior corneal surface, regardless of the calculation method. The
magnitudes of displacement of peripheral and central posterior corneal surfaces
were significantly smaller in the PRK-CXL group than in the PRK group. Moreover,
the PRK-CXL group showed a backward displacement of posterior corneal surface at
maximum corneal elevations when the BFTE was used as the reference surface.
CONCLUSIONS: Transepithelial PRK combined with prophylactic CXL significantly
reduced the magnitudes of displacement of peripheral and central posterior
corneal surfaces, with the radius of the BFTE was set to 8.0-mm on the
Scheimpflug tomography system.
PMID- 27502495
TI - Systematic Literature Review of DPP-4 Inhibitors in Patients with Type 2 Diabetes
Mellitus and Renal Impairment.
AB - INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used in the
management of patients with type 2 diabetes mellitus (T2DM) and renal impairment
(RI). A systematic literature review was performed to compare the efficacy and
safety of DPP-4 inhibitors in patients with T2DM and RI. METHODS: We searched
EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials (cut-off,
June 2015) to identify >=12-week, randomized, placebo-controlled trials on DPP-4
inhibitors in >=50 patients with T2DM and RI. Outcomes of interest included
change in glycated hemoglobin (HbA1c), overall safety, and incidence of
hypoglycemic events (HEs). RESULTS: Seven trials of <=52-54 weeks duration were
retrieved, which included one study each on vildagliptin, saxagliptin, and
sitagliptin, two on linagliptin, and the remaining two were extension studies of
vildagliptin and saxagliptin. Majority of patients were on insulin at baseline
(53-86%), except in the sitagliptin study, where approximately 11% received
insulin during the placebo-controlled phase. After 52 weeks, vildagliptin and
saxagliptin reduced HbA1c levels by 0.6-0.7% (baseline 7.8-8.4%) versus placebo
in the overall population. HbA1c reductions were similar at weeks 12 and 52. In
the 12-week, placebo-controlled phase, sitagliptin and linagliptin reduced mean
HbA1c by approximately 0.4% (baseline 7.7-8.1%) versus placebo. Rates of HEs with
DPP-4 inhibitors were not significantly different versus placebo in any study.
Rates of adverse events (AEs) and changes involving renal function were similar
in the active- and placebo-treated groups. CONCLUSION: These results suggest that
DPP-4 inhibitors have the potential to improve glycemic control in patients with
RI without increasing the risk of HEs or overall AEs. FUNDING: Novartis Pharma
AG.
PMID- 27502496
TI - Effective Utilization of Oral Hypoglycemic Agents to Achieve Individualized HbA1c
Targets in Patients with Type 2 Diabetes Mellitus.
AB - Type 2 diabetes is a progressive condition that may require the combination of
three oral treatments to achieve optimal glycemic management to prevent
microvascular and macrovascular complications whilst minimizing the risk of acute
complications and side effects or adverse reactions to treatments. With the
widening availability of treatment options and increasing importance of
individualized treatment pathways, including personalized HbA1c targets, this
article will explore the mode of action of currently available oral treatments,
factors to consider when individualizing HbA1c targets, the relevance of
estimated glomerular filtration rate assessment, and the importance of reviewing
the clinical impact of all treatment decisions.
PMID- 27502497
TI - Accuracy of patient-specific template-guided vs. free-hand fluoroscopically
controlled pedicle screw placement in the thoracic and lumbar spine: a randomized
cadaveric study.
AB - PURPOSE: Dorsal spinal instrumentation with pedicle screw constructs is
considered the gold standard for numerous spinal pathologies. Screw misplacement
is biomechanically disadvantageous and may create severe complications. The aim
of this study was to assess the accuracy of patient-specific template-guided
pedicle screw placement in the thoracic and lumbar spine compared to the free
hand technique with fluoroscopy. METHODS: Patient-specific targeting guides were
used for pedicle screw placement from Th2-L5 in three cadaveric specimens by
three surgeons with different experience levels. Instrumentation for each side
and level was randomized (template-guided vs. free-hand). Accuracy was assessed
by computed tomography (CT), considering perforations of <2 mm as acceptable
(safe zone). Time efficiency, radiation exposure and dependencies on surgical
experience were compared between the two techniques. RESULTS: 96 screws were
inserted with an equal distribution of 48 screws (50 %) in each group. 58 % (n =
28) of template-guided (without fluoroscopy) vs. 44 % (n = 21) of free-hand
screws (with fluoroscopy) were fully contained within the pedicle (p = 0.153).
97.9 % (n = 47) of template-guided vs. 81.3 % (n = 39) of free-hand screws were
within the 2 mm safe zone (p = 0.008). The mean time for instrumentation per
level was 01:14 +/- 00:37 for the template-guided vs. 01:40 +/- 00:59 min for the
free-hand technique (p = 0.013), respectively. Increased radiation exposure was
highly associated with lesser experience of the surgeon with the free-hand
technique. CONCLUSIONS: In a cadaver model, template-guided pedicle screw
placement is faster considering intraoperative instrumentation time, has a higher
accuracy particularly in the thoracic spine and creates less intraoperative
radiation exposure compared to the free-hand technique.
PMID- 27502499
TI - The Epidemiology of Staphylococcus aureus and Panton-Valentine Leucocidin (pvl)
in Central Australia, 2006-2010.
AB - BACKGROUND: The Central Australian Indigenous population has a high incidence of
Staphylococcus aureus bacteremia (SAB) but little is known about the local
molecular epidemiology. METHODS: Prospective observational study of bacteremic
and nasal colonizing S.aureus isolates between June 2006 to June 2010. All
isolates underwent single nucleotide polymorphism (SNP) genotyping and testing
for the presence of the Panton-Valentine Leucocidin (pvl) gene. RESULTS: Invasive
isolates (n = 97) were predominantly ST93 (26.6 %) and pvl positive (54.3 %),
which was associated with skin and soft tissue infections (OR 4.35, 95 % CI 1.16,
16.31). Non-multiresistant MRSA accounted for 31.9 % of bacteremic samples and
showed a trend to being healthcare associated (OR 2.16, 95 % CI 0.86, 5.40). Non
invasive isolates (n = 54) were rarely ST93 (1.9 %) or pvl positive (7.4 %).
CONCLUSIONS: In Central Australia, ST93 was the dominant S.aureus clone, and was
frequently pvl positive and associated with an aggressive clinical phenotype.
Whether non-nasal carriage is more important with invasive clones or whether
colonization occurs only transiently remains to be elucidated.
PMID- 27502500
TI - Epidemiological study of adult-onset Still's disease using a Japanese
administrative database.
AB - Adult-onset Still's disease (AOSD) is a rare disease, and large epidemiological
studies of this disease are limited. Furthermore, it has been difficult to show
the incidence and characteristics of severe AOSD complications due to the rarity
of this disease. The aim of our study was to describe the demographics of AOSD
and the incidence and characteristics of severe complications. Using a large
Japanese administrative database, we identified hospitalized patients with AOSD
and described the demographics. We also calculated the incidence of severe
complications (i.e., macrophage activation syndrome [MAS] and disseminated
intravascular coagulation [DIC]) and in-hospital mortality in AOSD patients, and
then analyzed the age-controlled difference between men and women. We identified
513 patients with AOSD (mean age: 53.1 years; women 64.1 %). According to the age
distribution, there was no distinct peak age. The thirties and the sixties were
relatively large age groups. There were 76 patients of AOSD with MAS or DIC
observed in this study. The incidence of severe complications was 14.8 %, 95 % CI
[11.9, 18.2]. Women were more likely to have severe complications than men after
controlling for age (odds ratio: 2.07; [1.14, 3.73]; p = 0.014). AOSD does not
predominantly affect young adults in our study population. Elderly AOSD patients
can be observed more than before due to global population aging. Severe
complications are more likely to occur in women than in men.
PMID- 27502501
TI - Clinical and Pathological Significance of ER Stress Marker (BiP/GRP78 and PERK)
Expression in Malignant Melanoma.
AB - Glucose-regulated protein of 78 kD (GRP78) also referred to as immunoglobulin
heavy chain binding protein (BiP/GRP78) plays an important role in the
endoplasmic reticulum (ER) stress. The level of BiP/GRP78 is highly elevated in
various human cancers. The purpose of this study is to examine the prognostic
significance of BiP/GRP78 expression in patients with malignant melanoma. A total
of 133 malignant melanoma patients were analyzed, and tumor specimens were
stained by immunohistochemistry for BiP/GRP78, PKR-like endoplasmic reticulum
kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34.
BiP/GRP78 and PERK were highly expressed in 40 % (53/133) and 78 % (104/133),
respectively. BiP/GRP78 disclosed a significant relationship with PERK
expression, thickness, T factor, N factor, disease staging, cell proliferation
(Ki-67) and MVD (CD34). By multivariate analysis, the high expression of
BiP/GRP78 was identified as an independent prognostic factor for predicting poor
survival against malignant melanoma. The increased BiP/GRP78 expression was
clarified as an independent prognostic marker for predicting worse outcome. ER
stress marker, BiP/GRP78 could be a powerful molecular target for the treatment
of malignant melanoma.
PMID- 27502502
TI - Risk Factors for Cryptococcal Meningitis: A Single United States Center
Experience.
AB - Cryptococcal meningitis carries a high mortality. Further understanding of immune
suppression factors associated with neuroinvasive infection will improve risk
stratification and enhance early diagnosis and treatment with antifungal therapy.
The aim of the study was to corroborate established or find novel clinical
predictors for cryptococcal meningitis. We performed a matched case-control study
of Cryptococcus infection in immunocompromised patients with or without
cryptococcal meningitis. Data of all patients with a diagnosis of cryptococcal
disease were collected at University of Colorado Hospital between 2000 and 2015
(n = 51). Thirty patients were diagnosed with cryptococcal meningitis. We built a
logistic regression model for risk factors associated with cryptococcal
meningitis. The single-predictor univariate model found that a positive blood
culture, positive serum cryptococcal antigen, current malignancy, and headaches
were significantly associated with cryptococcal meningitis (p = 0.02). In the
adjusted multivariate model, central nervous system disease was significantly
associated with a diagnosis of HIV infection (OR 24.45, 95 % CI 1.62-350.37; p =
0.022) and a positive serum cryptococcal antigen test (OR 42.92, 95 % CI 3.26
555.55; p = 0.0055). In patients with HIV infection or a positive serum
cryptococcal antigen, the pretest probability of neuroinvasive Cryptococcus
infection is increased and an aggressive diagnostic evaluation should be
conducted to exclude infection and consider empiric therapy.
PMID- 27502503
TI - New Antifungal Agents and New Formulations Against Dermatophytes.
AB - A variety of oral and topical antifungal agents are available for the treatment
of superficial fungal infections caused by dermatophytes. This review builds on
the antifungal therapy update published in this journal for the first special
issue on Dermatophytosis (Gupta and Cooper 2008;166:353-67). Since 2008, there
have not been additions to the oral antifungal armamentarium, with terbinafine,
itraconazole, and fluconazole still in widespread use, albeit for generally more
severe or recalcitrant infections. Griseofulvin is used in the treatment of tinea
capitis. Oral ketoconazole has fallen out of favor in many jurisdictions due to
risks of hepatotoxicity. Topical antifungals, applied once or twice daily, are
the primary treatment for tinea pedis, tinea corporis/tinea cruris, and mild
cases of tinea unguium. Newer topical antifungal agents introduced include the
azoles, efinaconazole, luliconazole, and sertaconazole, and the oxaborole,
tavaborole. Research is focused on developing formulations of existing topical
antifungals that utilize novel delivery systems in order to enhance treatment
efficacy and compliance.
PMID- 27502504
TI - Genetic Predictors of Susceptibility to Dermatophytoses.
AB - Countless observational studies conducted over the last century reveal that
dermatophytes infect humans of every age, race, gender, and socioeconomic status
with strikingly high rates. The curious disparity in dermatophyte infection
patterns observed within and between populations has led countless investigators
to explore whether genetics underlie a susceptibility to, or confer protection
against, dermatophyte infections. This paper examines the data that offer a link
between genetics and dermatophytoses and discusses the underlying mechanisms that
support these observations.
PMID- 27502505
TI - Evaluation of Daily Physical Activity (DPA) policy implementation in Ontario:
surveys of elementary school administrators and teachers.
AB - BACKGROUND: School-based structured opportunities for physical activity can
provide health-related benefits to children and youth, and contribute to
international guidelines recommending 60 min of moderate-to-vigorous physical
activity (MVPA) per day. In 2005, the Ministry of Education in Ontario, Canada,
released the Daily Physical Activity (DPA) policy requiring school boards to
"ensure that all elementary students, including students with special needs, have
a minimum of twenty minutes of sustained MVPA each school day during
instructional time". This paper reports on the first provincial study evaluating
implementation fidelity to the DPA policy in Ontario elementary schools and
classrooms. Using an adapted conceptual framework, the study also examined
associations between implementation of DPA and a number of predictors in each of
these respective settings. METHODS: Separate cross-sectional online surveys were
conducted in 2014 with Ontario elementary school administrators and classroom
teachers, based on a representative random sample of schools and classrooms. An
implementation fidelity score was developed based on six required components of
the DPA policy. Other survey items measured potential predictors of
implementation at the school and classroom levels. Descriptive analyses included
frequency distributions of implementation fidelity and predictor variables.
Bivariate analyses examining associations between implementation and predictors
included binary logistic regression for school level data and generalized linear
mixed models for classroom level data, in order to adjust for school-level
clustering effects. RESULTS: Among administrators, 61.4 % reported implementation
fidelity to the policy at the school level, while 50.0 % of teachers reported
fidelity at the classroom level. Several factors were found to be significantly
associated with implementation fidelity in both school and classroom settings
including: awareness of policy requirements; scheduling; monitoring; use of
resources and supports; perception that the policy is realistic and achievable;
and specific barriers to implementation. CONCLUSIONS: Findings from the surveys
indicate incomplete policy implementation and a number of factors significantly
associated with implementation fidelity. The results indicate a number of
important implications for policy, practice and further research, including the
need for additional research to monitor implementation and its predictors, and
assess the impacts of study recommendations and subsequent outcomes of a
reinvigorated DPA moving forward.
PMID- 27502507
TI - Critical illness polyneuropathy and myopathy 20 years later. No man's land? No,
it is our land!
PMID- 27502506
TI - The highly expressed 5'isomiR of hsa-miR-140-3p contributes to the tumor
suppressive effects of miR-140 by reducing breast cancer proliferation and
migration.
AB - BACKGROUND: miRNAs are small noncoding RNA molecules that play an important role
in post-transcriptional regulation of gene expression. Length and/or sequence
variants of the same miRNA are termed isomiRs. While most isomiRs are
functionally redundant compared to their canonical counterparts, the so-called
5'isomiRs exhibit a shifted 5' end and therefore a shifted seed sequence
resulting in a different target spectrum. However, not much is known about the
functional relevance of these isoforms. RESULTS: Analysis of miRNA-seq data from
breast cancer cell lines identified six pairs of highly expressed miRNAs and
associated 5'isomiRs. Among them, hsa-miR-140-3p was of particular interest
because its 5'isomiR showed higher expression compared to the canonical miRNA
annotated in miRbase. This miRNA has previously been shown to control stemness of
breast cancer cells. miRNAseq data of breast cancer patients (TCGA dataset)
showed that both the canonical hsa-miR-140-3p and its 5'isomiR-140-3p were highly
expressed in patients' tumors compared to normal breast tissue. In the current
work, we present the functional characterization of 5'isomiR-140-3p and the
cellular phenotypes associated with its overexpression in MCF10A, MDA-MB-468 and
MDA-MB-231 cell lines in comparison to the canonical hsa-miR-140-3p. Contrary to
the effect of the canonical hsa-miR-140-3p, overexpression of the 5'isomiR-140-3p
led to a decrease in cell viability. The latter observation was supported by cell
cycle analysis, where the 5'isomiR-140-3p but not the hsa-miR-140-3p caused cell
cycle arrest in G0/G1-phase. Additionally, 5'ismoiR-140-3p overexpression was
found to cause a decrease in cell migration in the three cell lines. We
identified three novel direct target genes of the 5'isomiR-140-3p; COL4A1, ITGA6
and MARCKSL1. Finally, we have shown that knocking down these genes partially
phenocopied the effects of the 5'isomiR-140-4p overexpression, where COL4A1 and
ITGA6 knockdown led to reduced cell viability and cell cycle arrest, while
MARCKSL1 knockdown resulted in a decrease in the migratory potential of cells.
CONCLUSIONS: In summary, this work presents evidence that there is functional
synergy between the canonical hsa-miR-140-3p and the newly identified 5'isomiR
140-3p in suppressing growth and progression of breast cancer by simultaneously
targeting genes related to differentiation, proliferation, and migration.
PMID- 27502508
TI - Increased risk for secondary infections in trauma patients with viral
reactivation.
PMID- 27502509
TI - Netrin-1 and its receptor Unc5b are novel targets for the treatment of
inflammatory arthritis.
AB - Rheumatoid arthritis is an autoimmune disease that is characterized by chronic
inflammation and destruction of joints. Netrin-1, a chemorepulsant, laminin-like
matrix protein, promotes inflammation by preventing macrophage egress from
inflamed sites and is required for osteoclast differentiation. We asked whether
blockade of Netrin-1 or its receptors [Unc5b and DCC (deleted in colorectal
carcinoma)] may be useful therapeutic targets for treatment of inflammatory
arthritis. Arthritis was induced in 8-wk-old C57Bl/6 mice by intraperitoneal
injection of K/BxN serum. Murine monoclonal antibodies against Netrin-1, Unc5b,
or DCC (10 ug/mouse) were injected weekly for 4 wk (n = 10). Paw swelling and
thickness were assessed and following euthanasia 2-4 wk after serum transfer,
paws were prepared for micro-computed tomography and histology. Paw inflammation
was maximal 2 wk after injection. Anti-Netrin-1 or anti-Unc5b, but not anti-DCC,
antibodies significantly reduced paw inflammation (clinical score: 9.8 +/- 0.8,
10.4 +/- 0.9, and 13.5 +/- 0.5, respectively vs 16 +/- 0 for control; P < 0.001).
Micro-computed tomography showed bony erosions in untreated or anti-DCC-treated
mice, whereas there were no erosions in anti-Netrin-1/anti-Unc5b-treated-animals.
Tartrate-resistant acid phosphatase staining demonstrated a marked decrease in
osteoclasts in anti-Netrin-1/anti-Unc5b-treated animals. Immunofluorescence
staining revealed a decrease in cathepsin K+ and CD68+ cells in anti-Netrin
1/anti-Unc5b-treated animals. Blockade of Netrin-1/Unc5b by monoclonal antibodies
prevents bone destruction and reduces the severity of K/BxN serum transfer
induced arthritis. Netrin-1 may be a novel therapeutic target for treatment of
inflammatory bone destruction.-Mediero, A., Wilder, T., Ramkhelawon, B., Moore,
K. J., Cronstein, B. N. Netrin-1 and its receptor Unc5b are novel targets for the
treatment of inflammatory arthritis.
PMID- 27502510
TI - The great recession, youth unemployment and inequalities in psychological health
complaints in adolescents: a multilevel study in 31 countries.
AB - OBJECTIVES: Little is known about the impact of recessions on young people's
socioeconomic inequalities in health. This study investigates the impact of the
economic recession in terms of youth unemployment on socioeconomic inequalities
in psychological health complaints among adolescents across Europe and North
America. METHODS: Data from the WHO collaborative 'Health Behaviour in School
aged Children' (HBSC) study were collected in 2005/06 (N = 160,830) and 2009/10
(N = 166,590) in 31 European and North American countries. Logistic multilevel
models were used to assess the contribution of youth unemployment in 2009/10
(enduring recession) and the change in youth unemployment (2005-2010) to
adolescent psychological health complaints and socioeconomic inequalities in
complaints in 2009/10. RESULTS: Youth unemployment during the recession is
positively related to psychological health complaints, but not to inequalities in
complaints. Changes in youth unemployment (2005-2010) were not associated with
adolescents' psychological health complaints, whereas greater inequalities in
complaints were found in countries with greater increases in youth unemployment.
CONCLUSIONS: This study highlights the need to tackle the impact of increasing
unemployment on adolescent health and health inequalities during economic
recessions.
PMID- 27502511
TI - Competition in the healthcare sector: a missing dimension.
PMID- 27502512
TI - Gain-of-Function Research: Ethical Analysis.
AB - Gain-of-function (GOF) research involves experimentation that aims or is expected
to (and/or, perhaps, actually does) increase the transmissibility and/or
virulence of pathogens. Such research, when conducted by responsible scientists,
usually aims to improve understanding of disease causing agents, their
interaction with human hosts, and/or their potential to cause pandemics. The
ultimate objective of such research is to better inform public health and
preparedness efforts and/or development of medical countermeasures. Despite these
important potential benefits, GOF research (GOFR) can pose risks regarding
biosecurity and biosafety. In 2014 the administration of US President Barack
Obama called for a "pause" on funding (and relevant research with existing US
Government funding) of GOF experiments involving influenza, SARS, and MERS
viruses in particular. With announcement of this pause, the US Government
launched a "deliberative process" regarding risks and benefits of GOFR to inform
future funding decisions-and the US National Science Advisory Board for
Biosecurity (NSABB) was tasked with making recommendations to the US Government
on this matter. As part of this deliberative process the National Institutes of
Health commissioned this Ethical Analysis White Paper, requesting that it provide
(1) review and summary of ethical literature on GOFR, (2) identification and
analysis of existing ethical and decision-making frameworks relevant to (i) the
evaluation of risks and benefits of GOFR, (ii) decision-making about the conduct
of GOF studies, and (iii) the development of US policy regarding GOFR (especially
with respect to funding of GOFR), and (3) development of an ethical and decision
making framework that may be considered by NSABB when analyzing information
provided by GOFR risk-benefit assessment, and when crafting its final
recommendations (especially regarding policy decisions about funding of GOFR in
particular). The ethical and decision-making framework ultimately developed is
based on the idea that there are numerous ethically relevant dimensions upon
which any given case of GOFR can fare better or worse (as opposed to there being
necessary conditions that are either satisfied or not satisfied, where all must
be satisfied in order for a given case of GOFR to be considered ethically
acceptable): research imperative, proportionality, minimization of risks,
manageability of risks, justice, good governance (i.e., democracy), evidence, and
international outlook and engagement. Rather than drawing a sharp bright line
between GOFR studies that are ethically acceptable and those that are ethically
unacceptable, this framework is designed to indicate where any given study would
fall on an ethical spectrum-where imaginable cases of GOFR might range from those
that are most ethically acceptable (perhaps even ethically praiseworthy or
ethically obligatory), at one end of the spectrum, to those that are most
ethically problematic or unacceptable (and thus should not be funded, or
conducted), at the other. The aim should be that any GOFR pursued (and/or funded)
should be as far as possible towards the former end of the spectrum.
PMID- 27502513
TI - A Breastfeeding Quality Improvement Project in Rural Primary Care.
AB - BACKGROUND: Breastfeeding is the gold standard nutrition for infants, and more
than three-fourths of US mother-infant couplets initiate breastfeeding at birth.
However, breastfeeding rates plummet after hospital discharge, when mother-infant
couplets enter primary care. This quality improvement project examined the effect
of a primary care intervention on breastfeeding rates from the newborn visit
through the 4-month visit. OBJECTIVE: The overall aim of this evidence-based
quality improvement project was to increase breastfeeding rates by refining the
care provided to a diverse patient population with historically low breastfeeding
rates. METHODS: Two independent groups of mother-infant couplets, a pre
implementation (N = 43) and a post-implementation (N = 45), were longitudinally
evaluated on breastfeeding rates at the newborn, 1-month, 2-month, and 4-month
well-child visits for exclusive, partial, and any breastfeeding rates.
Relationships for the 2 groups were compared using 2-sample t tests, chi-square,
and Fisher exact tests. RESULTS: Post-implementation rates for any breastfeeding
progressively increased at each timepoint. Exclusive breastfeeding increased
40.98% at the 1-month visit, 27.4% at the 2-month visit, and 139% at the 4-month
visit. CONCLUSION: The implementation of an evidence-based breastfeeding-friendly
office protocol in a rural low breastfeeding rate primary care setting was
associated with increased breastfeeding rates.
PMID- 27502514
TI - Community Rates of Breastfeeding Initiation.
AB - BACKGROUND: Breastfeeding initiation rates vary considerably across racial and
ethnic groups, maternal age, and education level, yet there are limited data
concerning the influence of geography on community rates of breastfeeding
initiation. OBJECTIVE: This study aimed to describe how community rates of
breastfeeding initiation vary in geographic space, highlighting "hot spots" and
"cool spots" of initiation and exploring the potential connections between race,
socioeconomic status, and urbanization levels on these patterns. METHODS: Birth
certificate data from the Kentucky Department of Health for 2004-2010 were
combined with county-level geographic base files, Census 2010 demographic and
socioeconomic data, and Rural-Urban Continuum Codes to conduct a spatial
statistical analysis of community rates of breastfeeding initiation. RESULTS:
Between 2004 and 2010, the average rate of breastfeeding initiation for Kentucky
increased from 43.84% to 49.22%. Simultaneously, the number of counties
identified as breastfeeding initiation hot spots also increased, displaying a
systematic geographic pattern in doing so. Cool spots of breastfeeding initiation
persisted in rural, Appalachian Kentucky. Spatial regression results suggested
that unemployment, income, race, education, location, and the availability of
International Board Certified Lactation Consultants are connected to
breastfeeding initiation. CONCLUSION: Not only do spatial analytics facilitate
the identification of breastfeeding initiation hot spots and cool spots, but they
can be used to better understand the landscape of breastfeeding initiation and
help target breastfeeding education and/or support efforts.
PMID- 27502519
TI - Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts'
Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.
AB - : : Restoration of the protein dystrophin on muscle membrane is the goal of many
research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of
ongoing preclinical and clinical trials suggest that partial restoration of
dystrophin might be sufficient to significantly reduce muscle damage. Different
myogenic progenitors are candidates for cell therapy of muscular dystrophies, but
only satellite cells and pericytes have already entered clinical experimentation.
This study aimed to provide in vitro quantitative evidence of the ability of
mesoangioblasts to restore dystrophin, in terms of protein accumulation and
distribution, within myotubes derived from DMD patients, using a microengineered
model. We designed an ad hoc experimental strategy to miniaturize on a chip the
standard process of muscle regeneration independent of variables such as
inflammation and fibrosis. It is based on the coculture, at different ratios, of
human dystrophin-positive myogenic progenitors and dystrophin-negative myoblasts
in a substrate with muscle-like physiological stiffness and cell micropatterns.
Results showed that both healthy myoblasts and mesoangioblasts restored
dystrophin expression in DMD myotubes. However, mesoangioblasts showed unexpected
efficiency with respect to myoblasts in dystrophin production in terms of the
amount of protein produced (40% vs. 15%) and length of the dystrophin membrane
domain (210-240 um vs. 40-70 um). These results show that our microscaled in
vitro model of human DMD skeletal muscle validated previous in vivo preclinical
work and may be used to predict efficacy of new methods aimed at enhancing
dystrophin accumulation and distribution before they are tested in vivo, reducing
time, costs, and variability of clinical experimentation. SIGNIFICANCE: This
study aimed to provide in vitro quantitative evidence of the ability of human
mesoangioblasts to restore dystrophin, in terms of protein accumulation and
distribution, within myotubes derived from patients with Duchenne muscular
dystrophy (DMD), using a microengineered model. An ad hoc experimental strategy
was designed to miniaturize on a chip the standard process of muscle regeneration
independent of variables such as inflammation and fibrosis. This microscaled in
vitro model, which validated previous in vivo preclinical work, revealed that
mesoangioblasts showed unexpected efficiency as compared with myoblasts in
dystrophin production. Consequently, this model may be used to predict efficacy
of new drugs or therapies aimed at enhancing dystrophin accumulation and
distribution before they are tested in vivo.
PMID- 27502520
TI - Characterization of hydrocarbons in aerosols at a Mediterranean city with a high
density of palm groves.
AB - Samples of PM1 and PM10 were collected for 1 year at an urban background station
in the city of Elche (southeastern Spain) and analyzed to determine the content
of n-alkanes and polycyclic aromatic hydrocarbons (PAHs). A few samples were also
gathered at a second sampling point established at one of the several palm tree
gardens of the city in order to evaluate the influence of biogenic emissions on
the urban levels of n-alkanes. Diagnostic parameters obtained for aliphatic
hydrocarbons (carbon maximum number (C max), carbon preference index (CPI), and
wax n-alkane content (%WNA)) revealed a higher contribution of biogenic n-alkanes
in PM10 than in PM1. Moreover, the values of %WNA indicated that the levels of n
alkanes in Elche were more affected by emissions from terrestrial vegetation than
in other urban areas, particularly in the palm tree grove location (%WNA = 29 for
PM10). PAH diagnostic ratios pointed to traffic as the main anthropogenic source
of hydrocarbons in Elche, with predominance of diesel versus gasoline vehicle
emissions. The average levels of total PAHs (~1 ng m(-3)) were noticeably lower
than the values registered at other urban areas in Europe, most likely because
emissions from other sources are scarce. Both aliphatic and aromatic hydrocarbons
showed higher levels in the cold season due to the lower atmospheric dispersion
conditions, the increase in traffic exhaust emissions, and the lower ambient
temperatures that reduce the evaporation of semivolatile species.
PMID- 27502521
TI - A multi-temporal analysis for change assessment and estimation of algal bloom in
Sambhar Lake, Rajasthan, India.
AB - Sambhar Lake in Rajasthan, India is the major inland salt water lake producing
salt for centuries. The present study addresses the monitoring changes in and
around the lake and its consequent effect on the lake water ecology. For this,
satellite images of the years 1976, 1981, 1997, and 2013 are analyzed for land
use land cover classes. Significant reduction in the water body is observed in
contrast with the increase in salt pan around the periphery of lake and wetland
classes. Further, the extent of water body and algae in the lake are delineated
as per normalized difference water index and normalized difference vegetation
index. Rainfall data do not indicate any major change in the pattern, but drastic
decrease in the extent of water body and significant increase in algal bloom are
serious concerns for the lake's existence. This may be due to surrounding
anthropogenic activities and construction of check dams and anicuts in the lake
catchment which curtail the runoff into the lake and provide favorable growth of
algae. Sambhar Lake, being declared as a wetland according to the Ramsar
Convention, is necessary to protect and conserve the ecological importance of the
lake through sustainable planning and management.
PMID- 27502522
TI - Polycyclic aromatic hydrocarbons in urban green spaces of Beijing: concentration,
spatial distribution and risk assessment.
AB - A comprehensive investigation of the levels, spatial distribution of polycyclic
aromatic hydrocarbons (PAHs) in urban green space soils of Beijing, China, was
conducted, and the potential human health risks associated with the levels
observed were addressed. The objective of this study was to determine
concentration, spatial distribution, and health risk of 15 PAHs in 121 surface
soil (0-5 cm) samples collected from four types of green space, such as park
green space (PGS), roadside green space (RDS), residential green space (RGS), and
attached green space (AGS). Results showed that the highest concentrations of 15
PAHs was in soils of RDS, followed by RGS, PGS, and AGS. The level of PAHs
pollution was seriously and mainly distributed in the central and southwest of
the city. Incremental lifetime cancer risks (ILCRs) associated with exposures to
PAHs in soil was calculated separately for children and adults under normal and
extreme conditions. The results showed that ILCRs for urban green space soil of
Beijing were low under normal conditions. But individual samples are seriously
polluted, and its potential health risks cannot be ignored.
PMID- 27502523
TI - Offline solid-phase extraction for preconcentration of pharmaceuticals and
personal care products in environmental water and their simultaneous
determination using the reversed phase high-performance liquid chromatography
method.
AB - The present study reports a precise and simple offline solid-phase extraction
(SPE) coupled with reversed-phase high-performance liquid chromatography (RP
HPLC) method for the simultaneous determination of five representative and
commonly present pharmaceuticals and personal care products (PPCPs), a new class
of emerging pollutants in the aquatic environment. The target list of analytes
including ciprofloxacin, acetaminophen, caffeine benzophenone and irgasan were
separated by a simple HPLC method. The column used was a reversed-phase C18
column, and the mobile phase was 1 % acetic acid and methanol (20:80 v/v) under
isocratic conditions, at a flow rate of 1 mL min(-1). The analytes were separated
and detected within 15 min using the photodiode array detector (PDA). The
linearity of the calibration curves were obtained with correlation coefficients
0.98-0.99.The limit of detection (LOD), limit of quantification (LOQ), precision,
accuracy and ruggedness demonstrated the reproducibility, specificity and
sensitivity of the developed method. Prior to the analysis, the SPE was performed
using a C18 cartridge to preconcentrate the targeted analytes from the
environmental water samples. The developed method was applied to evaluate and
fingerprint PPCPs in sewage collected from a residential engineering college
campus, polluted water bodies such as Nag river and Pili river and the influent
and effluent samples from a sewage treatment plant (STP) situated at Nagpur city,
in the peak summer season. This method is useful for estimation of pollutants
present in microquantities in the surface water bodies and treated sewage as
compared to nanolevel pollutants detected by mass spectrometry (MS) detectors.
PMID- 27502524
TI - Are Saudi medical students aware of middle east respiratory syndrome coronavirus
during an outbreak?
AB - Recently, an outbreak of MERS-CoV occurred in King Abdulaziz Medical City (KAMC),
Riyadh. This outbreak contributed to the students at the King Saud bin Abdulaziz
University for Health Sciences (KSAU-HS) becoming more involved in promoting
health awareness in their communities. This was a cross-sectional study that
evaluated students in the clinical phase of medical school. The data were
collected by an online questionnaire. The measurements were obtained using a
researcher-administered and a self-reported questionnaire that had been
previously validated. A p-value of less than 0.05 was considered statistically
significant. One hundred and thirty-six students participated and showed good
awareness regarding the clinical aspects of MERS, such as etiology, diagnosis,
management, and prevention. However, 76% of the students were not aware of the
mortality rate. Conversely, this study uncovered a low level of awareness in the
basic sciences. Interestingly, fifth year medical students were more familiar
with the incubation period than final year students (p-value <0.05). Regarding
gender differences, more female students were knowledgeable about the incubation
period and the possible asymptomatic presentation of the disease than male
students (p-value <0.05). However, male students were more aware of the
diagnostic tests for MERS than their female counterparts. Medical students were
knowledgeable about the clinical aspects of MERS but were lacking background
awareness in the basic sciences.
PMID- 27502525
TI - Police officers gunned down while protecting vaccination workers in Pakistan.
PMID- 27502526
TI - Prevalence and risk factors for viral blipping in chronic hepatitis B patients
treated with nucleos (t) ide analogues.
AB - The clinical relevance of viral blipping during nucleos (t) ide analogue (NA)
treatment is unclear in chronic hepatitis B (CHB). We investigated the
prevalence, risk factors and clinical outcomes for those with viral blipping
during NA treatment. A retrospective cohort study investigated consecutively
treated CHB patients from May 2008 to February 2015 on the NAs such as entecavir
(ETV), tenofovir (TDF) and lamivudine (LAM). Included patients were previously
treatment naive. Viral blipping was defined as serum HBV DNA >20 IU/mL on one
occasion, and not >200 IU/mL, with subsequent measurement returning to
undetectable levels, that is <20 IU/mL. A total of 242 treatment-compliant CHB
patients were included with 44 (18.2%) experiencing viral blipping. In
multivariable Cox regression, Asian race (HR=7.40, 95% CI 1.01-54.29, P<.049),
LAM therapy (vs ETV/TDF, HR=2.53, 95% CI 1.29-4.95, P<.007), higher creatinine
(per SD, HR=1.47, 95% CI 1.21-1.79, P<.001), HBeAg positivity (HR=2.68, 95% CI
1.39-5.03, P<.003) and longer time to achieve undetectable HBV DNA (per month,
HR=1.05, 95% CI 1.02-1.08, P=.001) were associated with an increased risk of
viral blipping. Viral blipping did not show any significant association with
viral breakthrough, HBsAg loss, ALT flares or disease progression. Viral blipping
is a frequent event during NA therapy; however, it did not lead to any clinically
significant outcomes. Thus, it may not require more frequent blood work and
patient visits in clinical practice.
PMID- 27502527
TI - Delirium in elderly patients: association with educational attainment.
AB - OBJECTIVE: Among cognitive reserve markers, educational attainment is the most
widely studied, with several studies establishing a strong association with risk
of dementia. However, it has not yet been fully examined in delirium. This study
aims to analyse the relationship between educational attainment and delirium.
METHODS: The study included elderly hospitalised patients admitted (>=48 h) into
an intermediate care unit (IMCU) of Intensive Care Medicine Service. Exclusion
criteria were as follows: Glasgow Coma Scale (total<=11), blindness/deafness,
inability to communicate or to speak Portuguese. The European Portuguese Version
of the Confusion Assessment Method (CAM) was used for delirium assessment.
RESULTS: The final sample (n=157) had a mean age of 78.8 (SD=7.6) the majority
being female (52.2%), married (51.5%) and with low educational level (49%).
According to CAM, 21% of the patients had delirium. The delirium group presented
the fewest years of education (median 1 vs. 4), with statistical significance
(p=0.003). Delirium was more frequent among male patients [odds ratio (OR) 0.32;
95% confidence interval (CI) 0.12-0.86; p=0.023], as well as those patients with
lower education (OR 0.76; 95% CI 0.62-0.95; p=0.016), and with respiratory
disease (OR 3.35; 95% CI 1.20-9.33; p=0.020), after controlling for age and
medication. CONCLUSION: Similar to previous studies, these findings point to a
negative correlation between education and delirium. This study appears as an
attempt to contribute to the knowledge about the role of cognitive reserve in
risk of delirium, particularly because is the first one that has been carried out
in an IMCU, with lower educated elderly patients. Further studies are needed to
clarify this relationship considering other markers (e.g. cognitive activities),
which can contribute to the definition of preventive strategies.
PMID- 27502528
TI - Weight gain in insulin-treated patients by body mass index category at treatment
initiation: new evidence from real-world data in patients with type 2 diabetes.
AB - AIMS: To evaluate, in patients with type 2 diabetes (T2DM) treated with insulin,
the extent of weight gain over 2 years of insulin treatment, and the dynamics of
weight gain in relation to glycaemic achievements over time according to
adiposity levels at insulin initiation. MATERIALS AND METHODS: Patients with T2DM
(n = 155 917), who commenced insulin therapy and continued it for at least 6
months, were selected from a large database of electronic medical records in the
USA. Longitudinal changes in body weight and glycated haemoglobin (HbA1c)
according to body mass index (BMI) category were estimated. RESULTS: Patients had
a mean age of 59 years, a mean HbA1c level of 9.5%, and a mean BMI of 35 kg/m2 at
insulin initiation. The HbA1c levels at insulin initiation were significantly
lower (9.2-9.4%) in the obese patients than in patients with normal body weight
(10.0%); however, the proportions of patients with HbA1c >7.5% or >8.0% were
similar across the BMI categories. The adjusted weight gain fell progressively
with increasing baseline BMI category over 6, 12 and 24 months (p < .01). The
adjusted changes in HbA1c were similar across BMI categories. A 1% decrease in
HbA1c was associated with progressively less weight gain as pretreatment BMI
rose, ranging from a 1.24 kg gain in those with a BMI <25 kg/m2 to a 0.32 kg loss
in those with a BMI > 40 kg/m2 . CONCLUSIONS: During 24 months of insulin
treatment, obese patients gained significantly less body weight than normal
weight and overweight patients, while achieving clinically similar glycaemic
benefits. These data provide reassurance with regard to the use of insulin in
obese patients.
PMID- 27502529
TI - Significance Testing Needs a Taxonomy: Or How the Fisher, Neyman-Pearson
Controversy Resulted in the Inferential Tail Wagging the Measurement Dog.
AB - Accurate measurement and a cutoff probability with inferential statistics are not
wholly compatible. Fisher understood this when he developed the F test to deal
with measurement variability and to make judgments on manipulations that may be
worth further study. Neyman and Pearson focused on modeled distributions whose
parameters were highly determined and concluded that inferential judgments
following an F test could be made with accuracy because the distribution
parameters were determined. Neyman and Pearson's approach in the application of
statistical analyses using alpha and beta error rates has played a dominant role
guiding inferential judgments, appropriately in highly determined situations and
inappropriately in scientific exploration. Fisher tried to explain the different
situations, but, in part due to some obscure wording, generated a long standing
dispute that currently has left the importance of Fisher's p < .05 criteria not
fully understood and a general endorsement of the Neyman and Pearson error rate
approach. Problems were compounded with power calculations based on effect sizes
following significant results entering into exploratory science. To understand in
a practical sense when each approach should be used, a dimension reflecting
varying levels of certainty or knowledge of population distributions is
presented. The dimension provides a taxonomy of statistical situations and
appropriate approaches by delineating four zones that represent how well the
underlying population of interest is defined ranging from exploratory situations
to highly determined populations.
PMID- 27502530
TI - The Taxonic Latent Structure and Taxometrics in Forensic Mental Health.
AB - Recently, researchers in the field of forensic mental health have attempted to
address the technical, empirical question of whether important clinical problems,
such as psychopathy or malingering, constitute taxa (i.e., discrete conditions).
In this paper, we provide a detailed elucidation of the foundational logic of the
quantitative methods employed to answer this question, focusing on the taxometric
procedures developed by Paul Meehl and colleagues. We attempt to demonstrate that
research on taxonicity is hampered by (a) researchers' unfamiliarity with or
misunderstanding of the logic underlying latent variable technologies and (b) the
fundamental incapacity of Meehlian procedures to provide a test of taxonicity. We
conclude by discussing the utility of taxometric procedures to research in
forensic mental health and, more broadly, in the field of applied psychological
measurement.
PMID- 27502531
TI - Males Perform Better in Identifying Voices During Menstruation Than Females: A
Pilot Study.
AB - The objective of the present study is to investigate gender differences in the
ability to identify females' voice during menstruation. In Study 1, 55 male
participants (M age = 19.6 years, SD = 1.0) were asked to listen to vocal samples
from women during both ovulation and menstruation and to identify which
recordings featured menstruating women. The results showed that the accuracy of
men's responses (M = 56.73%, SD = 0.21) was significantly higher than 50%. In
Study 2, 118 female students (M age = 19.4 years, SD = 1.6) completed the same
task. The results indicated that the accuracy of women's performance was nearly
50%. These preliminary findings suggest that men are better able to identify
women's voices during menstruation than women. Future work could consider several
significant variables for the purpose of validating the results.
PMID- 27502532
TI - A Brief Exploratory Report of Coping Strategies Among Police Recruits During
Academy Training.
AB - Few longitudinal studies have investigated the use of coping strategies among
police recruits. This study investigated perceived life and work stressors,
appraisal, and coping over a seven-month police recruit academy training program.
Participants were 81 police recruits who completed the Ways of Coping
Questionnaire at three time points approximately three months apart. The average
age of the recruits was 27.6 years (SD = 5.1, range 20-51). Separate repeated
measures analyses of variance were conducted to examine coping scores.
Statistically significant decreases, although small, were observed in reported
emotion-focused, problem-focused, and seeking social support coping strategies.
Results suggested that as police recruits undergo academy training, they rely on
fewer coping strategies to deal with life and work stress. More longitudinal
studies are needed that assess the methods police recruits utilize to manage
stress during academy training. Such results can inform stress management
interventions.
PMID- 27502533
TI - Impact of the DSM-V Attention Deficit Hyperactivity Disorder Criteria for
Diagnosing Children With High IQ.
AB - This study compared the number of attention deficit hyperactivity disorder (ADHD)
cases defined by Diagnostic and Statistical Manual (DSM)-IV versus DSM-V
criterion in children who have learning or behavioral problems with high IQ. The
medical records of children <=15 years of age who presented with learning or
behavioral problems and underwent a Wechsler Intelligence Scale for Children
(WISC)-III IQ test at the Pediatric Outpatient Clinic unit between 2010 and 2015
were reviewed. Information on DSM-IV and DSM-V criteria for ADHD were derived
from computer-based medical records. Twenty-eight children who had learning or
behavioral problems were identified to have a full-scale IQ >=120. Sixteen of
these high-IQ children met the DSM-IV criteria diagnosis for ADHD. Applying the
extension of the age-of-onset criterion from 7 to 12 years in DSM-V led to an
increase of three cases, all of which were the inattentive type ADHD. Including
the pervasive developmental disorder criterion led to an increase of one case.
The total number of ADHD cases also increased from 16 to 20 in this group. The
data supported the hypothesis that applying the extension of the age-of-onset
ADHD criterion and enabling the diagnosis of children with pervasive
developmental disorders will increase the number of ADHD diagnoses among children
with high IQ.
PMID- 27502534
TI - Effect of Acute Emotional Stress on Proteomic Profile of Selected Brain Areas and
Lysosomal Proteolysis in Rats with Different Behavioral Activity.
AB - We compared proteome profiles of selected brain areas (cortex, amygdala,
hippocampus, and reticular formation) and measured cathepsins B and D activity in
liver lysosomal fraction in rats with different behavioral activity under
conditions of emotional stress. In passive rats, the expression of some proteins
in various brain regions was changed and baseline cathepsin B activity was higher
than in active animals. Taken together, the results attest to differences in the
adaptive response formation in rats, depending on behavioral features.
PMID- 27502535
TI - Effect of Afobazole and Betaine on Cognitive Disorders in the Offspring of Rats
with Streptozotocin-Induced Diabetes and Their Relationship with DNA Damage.
AB - Cognitive activity in 60-day-old offspring of rats (intrauterine development in
experimental streptozotocin-induced diabetes) was studied on the model of food
seeking behavior under conditions of free choice in a 6-arm maze. The formation
of the food-procuring skill was significantly delayed, which attests to
impairment of cognitive functions in these animals. Peroral administration of
afobazole (10 and 50 mg/kg) and betaine (50 and 100 mg/kg) significantly and dose
dependently alleviated this disorder. Correlation analysis of the data on delayed
formation of a food-procuring skill and results of DNA comet attests to a strong
relationship between DNA damage in cells of the embryo and placenta during
intrauterine development and cognitive dysfunction in the postnatal offspring of
animals with streptozotocin-induced diabetes.
PMID- 27502536
TI - Antitumor Effects of JAK3 Inhibitor on the Model of Transplantable Lewis Lung
Carcinoma and Mechanisms of Their Development.
AB - Mice with Lewis lung carcinoma were used to study the antitumor and
antimetastatic effects of JAK3 inhibitor. The study revealed no effect of JAK3
inhibitor on the growth of primary tumor node, but found a pronounced inhibition
of hematogenous spread of the pathologic process into the lungs. In vitro
blockade of JAK3 in cultured Lewis lung carcinoma produced no effect on the count
of the stem tumor cells and stimulated functions of committed elements. In
addition, blockade of JAK3 significantly elevated maturation index of the tumor
tissue.
PMID- 27502537
TI - Enzyme Changes in the Offspring of Female Rats due to Long-Term Administration of
Cyclic AMP and Insulin before Pregnancy.
AB - We studied the effects of insulin and cAMP on the offspring of female rats after
daily treatment with these substances over 4 weeks. In adult offspring from cAMP
treated females, activities of pyruvate kinase and glucose-6-phosphate
dehydrogenase decreased in the liver and brain and activities of NADP-dependent
malate dehydrogenase and 6-phosphogluconate dehydrogenase decreased in the liver.
In the offspring of insulin-treated females, we observed only activation of
glucose-6-phosphate dehydrogenase and malate dehydrogenase in the liver and only
in females. Enzyme activity probably correlates with their content, as no changes
in their kinetic properties were observed under these conditions. Long-term
hormone treatment before pregnancy can affect the expression of genes for some
enzymes in the offspring due to transmission of epigenetic signals by the ovum.
However, further studies are required to confirm this mechanism.
PMID- 27502538
TI - Evidence of Echocardiography Validity in Model Experiments on Small Animals.
AB - Dynamic echocardiographic monitoring in rats subjected to forced alcoholization
showed the formation of disorders in intracardiac hemodynamics characteristic of
ethanol cardiomyopathy formed by the end of 24-week continuous ethanol
consumption. The results of echocardiographic monitoring were confirmed by
histological and morphometric studies demonstrating fatty infiltration of the
myocardium pathognomonic for this condition and bifocal dilatation of cardiac
ventricles. These results persuasively demonstrate that echocardiographic studies
on small animals are valid and can be used for search for cardiotropic drugs and
studies of the mechanisms of their activities.
PMID- 27502539
TI - Studying the General Toxicity and Cumulative Properties of a Radiopharmaceutical
Nanocolloid, (99m)Tc-Al2O3.
AB - We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc
Al2O3. Tests for acute toxicity showed that this agent belongs to a class of
moderate-toxicity substances and does not have cumulative properties. The
evaluation of subchronic toxicity after subcutaneous injection of this product to
rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did
not reveal changes in the general state, temperature, body weight, indices of the
peripheral blood and bone marrow, functions of the heart, liver, kidneys, and
nervous system, and morphological characteristics of the internal organs in
animals. The drug does not produce a local irritant effect.
PMID- 27502540
TI - Investigation of anti-asthmatic potential of Kanakasava in ovalbumin-induced
bronchial asthma and airway inflammation in rats.
AB - ETHNO-PHARMACOLOGICAL RELEVANCE: Kanakasava is an Indian traditional Ayurvedic
formulation containing Datura (Datura metel), Vasaca (Adhatoda vasica), Dhataki
(Woodfordia fruticosa) and Grape (Vitis vinifera) extracts as major constituents
and used to treat pulmonary diseases including coughing, breathing difficulty and
asthma. The present study was designed to assess the safety and therapeutic
efficacy of Kanakasava against ovalbumin-induced bronchial asthma and related
airway inflammation in rats due to lack of evidence based therapeutic efficacy
data. MATERIAL AND METHODS: Male wistar rats were sensitized with allergen
(ovalbumin, 40mg/rat+aluminum hydroxide, 2.0mg/rat) and treated orally with
standard dexamethasone (2.5mg/kg, b.w.) or Kanakasava (1.23 and 2.46ml/kg, b.w.)
from day 1 to day 28. Inflammatory markers, including cell counts and cytokines
such as interleukins (IL-4, IL-5, IL-1beta), tumor necrosis factor (TNF-alpha),
leukotriene (LTD-4), immunoglobulin (IgE), nitric oxide and nitrite levels in
both blood and broncheo alveolar lavaged fluid (BALF) were analyzed. Abdominal
mesentery was studied histologically for mast cell degranulation, whereas lung
functions were investigated by spirometer. Method was also developed to quantify
gallic acid and ethyl gallate content in Kanakasava by HPTLC for its quality
control. RESULTS: None of the rats exhibited mortality and Kanakasava was found
to be safe at the tested doses. Treatment with Kanakasava significantly (P<0.01)
reversed elevated levels of IgE, cytokines, nitrites and influx of eosinophils
and neutrophils in blood and BALF. These findings were further supported by the
significant improvement in lung functions (P<0.01) and suppression (P<0.01) of
degranulation of mast cells. The content of gallic acid and ethyl gallate in
Kanakasava was found to be 1.94% and 0.98%, respectively. CONCLUSION: These
findings demonstrated the preventive effect of Kanakasava in allergen induced
model of asthma providing scientific basis for its traditional use in Ayurveda,
since long time.
PMID- 27502541
TI - Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo
Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors.
AB - Cancer Osaka thyroid (COT) kinase is an important regulator of pro-inflammatory
cytokines in macrophages. Thus, pharmacologic inhibition of COT should be a valid
approach to therapeutically intervene in the pathogenesis of macrophage-driven
inflammatory diseases such as rheumatoid arthritis. We report the discovery and
chemical optimization of a novel series of COT kinase inhibitors, with
unprecedented nanomolar potency for the inhibition of TNFalpha. Pharmacological
profiling in vivo revealed a high metabolism of these compounds in rats which was
demonstrated to be predominantly attributed to aldehyde oxidase. Due to the very
low activity of hepatic AO in the dog, the selected candidate 32 displayed
significant blood exposure in dogs which resulted in a clear prevention of
inflammation-driven lameness. Taken together, the described compounds both
potently and selectively inhibit COT kinase in primary human cells and ameliorate
inflammatory pathologies in vivo, supporting the notion that COT is an
appropriate therapeutic target for inflammatory diseases.
PMID- 27502542
TI - Calpains are involved in asexual and sexual development, cell wall integrity and
pathogenicity of the rice blast fungus.
AB - Calpains are ubiquitous and well-conserved proteins that belong to the calcium
dependent, non-lysosomal cysteine protease family. In this study, 8 putative
calpains were identified using Pfam domain analysis and BlastP searches in M.
oryzae. Three single gene deletion mutants (DeltaMocapn7, DeltaMocapn9 and
DeltaMocapn14) and two double gene deletion mutants (DeltaMocapn4DeltaMocapn7 and
DeltaMocapn9DeltaMocapn7) were obtained using the high-throughput gene knockout
system. The calpain disruption mutants showed defects in colony characteristics,
conidiation, sexual reproduction and cell wall integrity. The mycelia of the
DeltaMocapn7, DeltaMocapn4DeltaMocapn7 and DeltaMocapn9DeltaMocapn7 mutants
showed reduced pathogenicity on rice and barley.
PMID- 27502543
TI - Computer simulations of a new toroidal-cylindrical ion trap mass analyzer.
AB - RATIONALE: A novel toroidal-cylindrical ion trap (TCIT) design is introduced
based on a compact dual ion trap system that comprises an outer toroidal ion trap
(T-trap) and an inner cylindrical ion trap (CIT). These two traps have specific
but different functions that can improve the performance of tandem mass analysis
operation. METHODS: The TCIT is studied by using a simulated mass spectrometer
platform that is mainly based on SIMION modeling and extensive data processing.
This platform combines different functions, such as simulation of ion motion and
field calculations, as well as acquisition of a simulated mass spectrum. RESULTS:
The main steps of the MS operation, including the full scan process, the mass
selective ejection of the ions in the T-trap, and the capture of the injected
precursor ions in the CIT, are realized using the abovementioned platform. In
addition, the simulated design is optimized for improved mass analysis
performance. CONCLUSIONS: For the outer T-trap, when the outside surface of the
inner cylindrical electrode is modified to include a circular arc with
appropriate radius, the ion ejection efficiency that is directed into the CIT
could be significantly enhanced. In the case of the inner CIT, the ion capture
efficiency could be improved to more than 90% with geometry optimization.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27502545
TI - Evaluation of VDR gene polymorphisms in Trypanosoma cruzi infection and chronic
Chagasic cardiomyopathy.
AB - Vitamin D is an important modulator of the immune response. It acts over several
immune cell types where the Vitamin D receptor (VDR) is expressed. Due to the
high relevance of this signaling pathway, several studies have investigated the
possible influence of genes involved in the metabolism of Vitamin D and its
receptor in different human diseases. Here, we analyzed whether four single
nucleotide polymorphisms of the VDR gene (rs731236, rs7975232, rs1544410 and
rs2228570) are involved in the susceptibility to infection by Trypanosoma cruzi
and/or to chronic Chagas cardiomyopathy (CCC) in a Colombian endemic population
for this parasite. Our results showed that the rs2228570*A allele is associated
with CCC development (P = 4.46E-03, OR = 1.51). In summary, the data presented in
this report suggest that variation within the VDR gene may affect the immune
response against T. cruzi, increasing the probability of cardiac complications in
infected individuals.
PMID- 27502546
TI - Evolution of Insulator-Metal Phase Transitions in Epitaxial Tungsten Oxide Films
during Electrolyte-Gating.
AB - An interface between an oxide and an electrolyte gives rise to various processes
as exemplified by electrostatic charge accumulation/depletion and electrochemical
reactions such as intercalation/decalation under electric field. Here we directly
compare typical device operations of those in electric double layer transistor
geometry by adopting A-site vacant perovskite WO3 epitaxial thin films as a
channel material and two different electrolytes as gating agent. In situ
measurements of X-ray diffraction and channel resistance performed during the
gating revealed that in both the cases WO3 thin film reaches a new metallic state
through multiple phase transitions, accompanied by the change in out-of-plane
lattice constant. Electrons are electrostatically accumulated from the interface
side with an ionic liquid, while alkaline metal ions are more uniformly
intercalated into the film with a polymer electrolyte. We systematically
demonstrate this difference in the electrostatic and electrochemical processes,
by comparing doped carrier density, lattice deformation behavior, and time
constant of the phase transitions.
PMID- 27502547
TI - Transplantation: GoCAR - on the road to reduced allograft loss.
PMID- 27502548
TI - Contemporary evidence for robot-assisted radical cystectomy for treating bladder
cancer.
AB - Robot-assisted radical cystectomy (RARC) is an evolving technique for the
treatment of muscle-invasive bladder cancer (MIBC); however, its effectiveness
compared with open radical cystectomy (ORC) - the established modality - is
debated. Six specific areas of evidence are critically important for supporting
the continuing use of RARC for MIBC, including technical aspects of surgery,
perioperative outcomes, complications, oncological outcomes, functional outcomes,
and financial costs. Considerable progress has been made regarding these aspects
and data show that RARC replicates the technical benchmarks of ORC in terms of
success of cystectomy, lymph node dissection, and urinary diversion, and could
offer advantages over the more-established technique. Despite some clear benefits
of RARC (such as reduced blood loss) other perioperative outcomes, including
duration of inpatient stay and 30-90 day complication rates, seem to be similar
to those of ORC. Current data on oncological and functional outcomes are
promising, but robust data from prospective studies will help determine the
indications for use of RARC for treating MIBC in the future.
PMID- 27502549
TI - Kidney cancer: Open gates for oxaliplatin.
PMID- 27502550
TI - Prostate cancer: Focal laser ablation improves short-term outcomes.
PMID- 27502551
TI - Panels of chemically-modified heparin polysaccharides and natural heparan sulfate
saccharides both exhibit differences in binding to Slit and Robo, as well as
variation between protein binding and cellular activity.
AB - Heparin/heparan sulfate (HS) glycosaminoglycans are required for Slit-Robo
cellular responses. Evidence exists for interactions between each combination of
Slit, Robo and heparin/HS and for formation of a ternary complex. Heparin/HS are
complex mixtures displaying extensive structural diversity. The relevance of this
diversity has been studied to a limited extent using a few select chemically
modified heparins as models of HS diversity. Here we extend these studies by
parallel screening of structurally diverse panels of eight chemically-modified
heparin polysaccharides and numerous natural HS oligosaccharide chromatographic
fractions for binding to both Drosophila Slit and Robo N-terminal domains and for
activation of a chick retina axon response to the Slit fragment. Both the
polysaccharides and oligosaccharide fractions displayed variability in binding
and cellular activity that could not be attributed solely to increasing
sulfation, extending evidence for the importance of structural diversity to
natural HS as well as model modified heparins. They also displayed differences in
their interactions with Slit compared to Robo, with Robo preferring compounds
with higher sulfation. Furthermore, the patterns of cellular activity across
compounds were different to those for binding to each protein, suggesting that
biological outcomes are selectively determined in a subtle manner that does not
simply reflect the sum of the separate interactions of heparin/HS with Slit and
Robo.
PMID- 27502552
TI - Oral sildenafil as a treatment option for lymphatic malformations in PIK3CA
related tissue overgrowth syndromes.
AB - Patients with extensive lymphatic malformations associated with tissue overgrowth
syndromes (such as Klippel-Trenaunay syndrome and CLOVES) often pose a
therapeutic challenge for physicians. In recent years, it has been suggested that
oral sildenafil therapy might be used to treat congenital lymphatic
malformations. However, this possible new therapy has not yet been used in
patients with lymphatic malformations associated with tissue overgrowth
syndromes. A 30-year-old man with extensive capillary-lymphatic malformations of
the right leg and thorax, and a tissue overgrowth syndrome caused by a somatic
mutation in the PIK3CA gene, was treated with oral sildenafil due to symptoms of
pain, dyspnea, and functional impairment. Several weeks after the start of the
treatment, the patient reported softening of the lymphatic malformation and a
significant improvement of his symptoms and physical condition. So far,
sildenafil is still considered a last resort in the treatment of complex
treatment-resistant lymphatic malformations. With this case report, we
demonstrate that sildenafil could also be an alternative treatment option for
lymphatic malformations in patients with syndromes belonging to the PIK3CA
related overgrowth spectrum.
PMID- 27502553
TI - Closed-state inactivation involving an internal gate in Kv4.1 channels modulates
pore blockade by intracellular quaternary ammonium ions.
AB - Voltage-gated K(+) (Kv) channel activation depends on interactions between
voltage sensors and an intracellular activation gate that controls access to a
central pore cavity. Here, we hypothesize that this gate is additionally
responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv
channels undergo CSI by a mechanism that is still poorly understood. To test the
hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by
exploiting the trap-door paradigm of pore blockade by internally applied
quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity
for a blocking site. We found that inactivation gating seemingly traps benzyl
tributylammonium (bTBuA) when it enters the central pore cavity in the open
state. However, bTBuA fails to block inactivated Kv4.1 channels, suggesting gated
access involving an internal gate. In contrast, bTBuA blockade of a Shaker Kv
channel that undergoes open-state P/C-type inactivation exhibits fast onset and
recovery inconsistent with bTBuA trapping. Furthermore, the inactivated Shaker Kv
channel is readily blocked by bTBuA. We conclude that Kv4.1 closed-state
inactivation modulates pore blockade by QA ions in a manner that depends on the
state of the internal activation gate.
PMID- 27502554
TI - Complementary mechanisms create direction selectivity in the fly.
AB - How neurons become sensitive to the direction of visual motion represents a
classic example of neural computation. Two alternative mechanisms have been
discussed in the literature so far: preferred direction enhancement, by which
responses are amplified when stimuli move along the preferred direction of the
cell, and null direction suppression, where one signal inhibits the response to
the subsequent one when stimuli move along the opposite, i.e. null direction.
Along the processing chain in the Drosophila optic lobe, directional responses
first appear in T4 and T5 cells. Visually stimulating sequences of individual
columns in the optic lobe with a telescope while recording from single T4
neurons, we find both mechanisms at work implemented in different sub-regions of
the receptive field. This finding explains the high degree of directional
selectivity found already in the fly's primary motion-sensing neurons and marks
an important step in our understanding of elementary motion detection.
PMID- 27502555
TI - Conserved functional antagonism of CELF and MBNL proteins controls stem cell
specific alternative splicing in planarians.
AB - In contrast to transcriptional regulation, the function of alternative splicing
(AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively
regulate an exon program specific of embryonic stem cells; however, little is
known about the in vivo significance of this regulation. We studied AS in a
powerful in vivo model for stem cell biology, the planarian Schmidtea
mediterranea. We discover a conserved AS program comprising hundreds of
alternative exons, microexons and introns that is differentially regulated in
planarian stem cells, and comprehensively identify its regulators. We show that
functional antagonism between CELF and MBNL factors directly controls stem cell
specific AS in planarians, placing the origin of this regulatory mechanism at the
base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal
regenerative capacities by affecting self-renewal and differentiation sets of
genes, respectively. These results highlight the importance of AS interactions in
stem cell regulation across metazoans.
PMID- 27502556
TI - Physical association between a novel plasma-membrane structure and centrosome
orients cell division.
AB - In the last mitotic division of the epidermal lineage in the ascidian embryo, the
cells divide stereotypically along the anterior-posterior axis. During
interphase, we found that a unique membrane structure invaginates from the
posterior to the centre of the cell, in a microtubule-dependent manner. The
invagination projects toward centrioles on the apical side of the nucleus and
associates with one of them. Further, a cilium forms on the posterior side of the
cell and its basal body remains associated with the invagination. A laser
ablation experiment suggests that the invagination is under tensile force and
promotes the posterior positioning of the centrosome. Finally, we showed that the
orientation of the invaginations is coupled with the polarized dynamics of
centrosome movements and the orientation of cell division. Based on these
findings, we propose a model whereby this novel membrane structure orchestrates
centrosome positioning and thus the orientation of cell division axis.
PMID- 27502558
TI - Cellular fingers take hold.
AB - Invaginations in the membranes of embryonic cells appear to orient cell division
in sea squirts.
PMID- 27502557
TI - Impact of HIV co-infection on the evolution and transmission of multidrug
resistant tuberculosis.
AB - The tuberculosis (TB) epidemic is fueled by a parallel Human Immunodeficiency
Virus (HIV) epidemic, but it remains unclear to what extent the HIV epidemic has
been a driver for drug resistance in Mycobacterium tuberculosis (Mtb). Here we
assess the impact of HIV co-infection on the emergence of resistance and
transmission of Mtb in the largest outbreak of multidrug-resistant TB in South
America to date. By combining Bayesian evolutionary analyses and the
reconstruction of transmission networks utilizing a new model optimized for TB,
we find that HIV co-infection does not significantly affect the transmissibility
or the mutation rate of Mtb within patients and was not associated with increased
emergence of resistance within patients. Our results indicate that the HIV
epidemic serves as an amplifier of TB outbreaks by providing a reservoir of
susceptible hosts, but that HIV co-infection is not a direct driver for the
emergence and transmission of resistant strains.
PMID- 27502559
TI - Effective antigen presentation to helper T cells by human eosinophils.
AB - Although eosinophils are inflammatory cells, there is increasing attention on
their immunomodulatory roles. For example, murine eosinophils can present antigen
to CD4+ T helper (Th) cells, but it remains unclear whether human eosinophils
also have this ability. This study determined whether human eosinophils present a
range of antigens, including allergens, to activate Th cells, and characterized
their expression of MHC class II and co-stimulatory molecules required for
effective presentation. Human peripheral blood eosinophils purified from non
allergic donors were pulsed with the antigens house dust mite extract (HDM),
Timothy Grass extract (TG) or Mycobacterium tuberculosis purified protein
derivative (PPD), before co-culture with autologous CD4+ Th cells. Proliferative
and cytokine responses were measured, with eosinophil expression of HLA-DR/DP/DQ
and the co-stimulatory molecules CD40, CD80 and CD86 determined by flow
cytometry. Eosinophils pulsed with HDM, TG or PPD drove Th cell proliferation,
with the response strength dependent on antigen concentration. The cytokine
responses varied with donor and antigen, and were not biased towards any
particular Th subset, often including combinations of pro- and anti-inflammatory
cytokines. Eosinophils up-regulated surface expression of HLA-DR/DP/DQ, CD80,
CD86 and CD40 in culture, increases that were sustained over 5 days when
incubated with antigens, including HDM, or the major allergens it contains, Der p
I or Der p II. Human eosinophils can, therefore, act as effective antigen
presenting cells to stimulate varied Th cell responses against a panel of
antigens including HDM, TG or PPD, an ability that may help to determine the
development of allergic disease.
PMID- 27502560
TI - Endothelial Progenitor Cells as Shuttle of Anticancer Agents.
AB - Cell therapies are treatments in which stem or progenitor cells are stimulated to
differentiate into specialized cells able to home to and repair damaged tissues.
After their discovery, endothelial progenitor cells (EPCs) stimulated worldwide
interest as possible vehicles to perform autologous cell therapy of tumors.
Taking into account the tumor-homing properties of EPCs, two different approaches
to control cancer progression have been pursued by combining cell-based therapy
with gene therapy or with nanomedicine. The first approach is based on the
possibility of engineering EPCs to express different transgenes, and the second
is based on the capacity of EPCs to take up nanomaterials. Here we review the
most important progress covering the following issues: the characterization of
bona fide endothelial progenitor cells, their role in tumor vascularization and
metastasis, and preclinical data about their use in cell-based tumor therapy,
considering antiangiogenic, suicide, immune-stimulating, and oncolytic virus gene
therapy. The mixed approach of EPC cell therapy and nanomedicine is discussed in
terms of plasmonic-dependent thermoablation and molecular imaging.
PMID- 27502561
TI - Oncologist, patient, and companion questions during pretreatment consultations
about adjuvant cancer treatment: a shared decision-making perspective.
AB - OBJECTIVES: To assess the occurrence of questions that foster shared decision
making, in particular cancer patients' understanding of treatment decisions and
oncologists' understanding of patients' priorities, during consultations in which
preference-sensitive decisions are discussed. Specifically, (a) regarding patient
understanding, do oncologists ask about patients' preexisting knowledge,
information preferences, and understanding and do patients and companions ask
about the disease and treatment, and (b) regarding patient priorities, do
oncologists ask about patients' treatment- and decision-related preferences and
do patients and companions ask about the decision? METHODS: Audiotaped
pretreatment consultations of 100 cancer patients with 32 oncologists about
(neo)adjuvant treatment were coded and analyzed to document question type, topic,
and initiative. RESULTS: The oncologists ascertained prior knowledge in 50
patients, asked 24 patients about preferred (probability) information, and
invited questions from 56 patients. The oncologists asked 32 patients about
treatment preferences and/or for consent. Respectively, one-third and one-fifth
of patients and companions asked about treatment benefits compared with three
quarters of them who asked about treatment harms and/or procedures. CONCLUSIONS:
It would be helpful to patients if oncologists more often assessed patients'
existing knowledge to tailor their information provision. Also, patients could
receive treatment recommendations that better fit their personal situation if
oncologists collected information on patients' views about treatments. Moreover,
by educating patients to ask about treatment alternatives, benefits, and harms,
patients may gain a better understanding of the choice they have.
PMID- 27502562
TI - Prevalence of bacterial resistance within an eco-agricultural system in Hangzhou,
China.
AB - The wide use of antibiotics in the animal husbandry and the relevant sustainable
industries may promote the emergence of antibiotic-resistant bacteria (ARB),
which constitutes a growing threat to human health. The objective of this study
was to determine the abundance and diversity of sulfonamide- and tetracycline
resistant bacteria within an eco-agricultural system (EAS) in Hangzhou, China. We
investigated samples at every link in the EAS, from livestock manure, to biogas
residues and biogas slurry, to vegetable and ryegrass fields, to a fish pond. A
combination of culture-based and 16S rRNA gene-based sequencing method was used
in this study. Within the studied system, the average rate of bacterial
resistance to sulfonamide (46.19 %) was much higher than that of tetracycline
(8.51 %) (p < 0.01). There were 224 isolates that were enumerated and sequenced,
108 of which were identified to species level. The genera comprising the
sulfamethoxazole-resistant (SMXr) bacteria were generally different from those of
tetracycline-resistant (TCr) bacteria. Staphylococcus and Acinetobacter were the
most dominant genera of SMXr bacteria (19.30 % of the total resistant bacteria)
and TCr bacteria (14.04 % of the total resistant bacteria), respectively. Several
strains of resistant opportunistic pathogens (e.g., Pantoea agglomerans) were
detected in edible vegetable samples, which may exert a potential threat to both
pig production and human health. In general, this study indicates that the EAS is
an important reservoir of antibiotic-resistant bacteria, some of which may be
pathogenic.
PMID- 27502563
TI - Periphyton: an important regulator in optimizing soil phosphorus bioavailability
in paddy fields.
AB - Periphyton is ubiquitous in paddy field, but its importance in influencing the
bioavailability of phosphorus (P) in paddy soil has been rarely recognized. A
paddy field was simulated in a greenhouse to investigate how periphyton
influences P bioavailability in paddy soil. Results showed that periphyton
colonizing on paddy soil greatly reduced P content in paddy floodwater but
increased P bioavailability of paddy soil. Specifically, all the contents of
water-soluble P (WSP), readily desorbable P (RDP), algal-available P (AAP), and
NaHCO3-extractable P (Olsen-P) in paddy soil increased to an extent compared to
the control (without periphyton) after fertilization. In particular, Olsen-P was
the most increased P species, up to 216 mg kg-1 after fertilization, accounting
for nearly 60 % of total phosphorus (TP) in soil. The paddy periphyton captured P
up to 1.4 mg g-1 with Ca-P as the dominant P fraction and can be a potential crop
fertilizer. These findings indicated that the presence of periphyton in paddy
field benefited in improving P bioavailability for crops. This study provides
valuable insights into the roles of periphyton in P bioavailability and migration
in a paddy ecosystem and technical support for P regulation.
PMID- 27502565
TI - Comparative study of different carbon-supported Fe2O3-Pt catalysts for oxygen
reduction reaction.
AB - One of the challenges in electrocatalysis is the adequate dispersion of the
catalyst on an appropriate porous support matrix, being up to now the most
commonly used the carbon-based supports. To overcome this challenge, carbon
supports must first be functionalized to guide the catalyst's nucleation,
thereby, improving the dispersion and allowing the use of smaller amount of the
catalyst material to achieve a higher electrochemically active surface area. This
study present the effect of functionalized Vulcan carbon XC72 (FVC) and
functionalized Black Pearl carbon (FBPC) as supports on the catalytic activity of
decorated Fe2O3 with Pt. Both carbons were functionalized with HNO3 and
subsequently treated with ethanolamine. Fe2O3 nanoparticles were synthesized by
chemical reduction and decorated with platinum by epitaxial growth. Pt and Fe2O3
structural phases were identified by XRD and XPS; the Pt content was measured by
XPS, and results showed to a high Pt content in Fe2O3-Pt/FBPC. TEM micrographs
reveal nanoparticles with an average size of 2 nm in both supported catalysts.
The Fe2O3-Pt/FVC catalyst presents the highest specific activity and mass
activity, 0.21 mA cm-2Pt and 140 mA mgPt-1, respectively, associated to the
appropriate distribution of platinum on the Fe2O3 nanoparticles.
PMID- 27502564
TI - Biochar enhances the cadmium tolerance in spinach (Spinacia oleracea) through
modification of Cd uptake and physiological and biochemical attributes.
AB - Cadmium (Cd) has no known role in plant biology and is toxic to plants and
animals. The Cd mainly accumulated in agricultural soils through anthropogenic
activities, such as sewage water irrigation and phosphorus fertilization. Biochar
(BC) has been proposed as an amendment to reduce metal toxicity in plants. The
objective of this study was to evaluate the role of BC (cotton stick at a rate of
0, 3, and 5 %) on Cd uptake and the photosynthetic, physiological, and
biochemical responses of spinach (Spinacia oleracea) grown in Cd-spiked soil (0,
25, 50, 75, and 100 mg Cd kg-1 soil). The results showed that Cd toxicity
decreased growth, photosynthetic pigments, gas exchange characteristics, and
amino acid and protein contents in 52-day-old spinach seedlings. The Cd
treatments increased the concentrations of Cd, sugar, ascorbic acid, and
malondialdehyde (MDA) in plants. The application of BC ameliorated the harmful
effects of Cd in spinach plants. Under Cd stress, BC application increased the
growth, photosynthesis, and protein contents and decreased Cd concentrations and
MDA contents in plants. The maximum BC-mediated increase in dry biomass was about
25 % with 5 % BC application in control plants. It is concluded that BC could
ameliorate Cd toxic effects in spinach through changing the physiological and
biochemical attributes under Cd stress.
PMID- 27502566
TI - Photocatalytic performance of electrospun CNT/TiO2 nanofibers in a simulated air
purifier under visible light irradiation.
AB - The photocatalytic treatment of gaseous benzene under visible light irradiation
was developed using electrospun carbon nanotube/titanium dioxide (CNT/TiO2)
nanofibers as visible light active photocatalysts. The CNT/TiO2 nanofibers were
fabricated by electrospinning CNT/poly(vinyl pyrrolidone) (PVP) solution followed
by the removal of PVP by calcination at 450 degrees C. The molar ratio of
CNT/TiO2 was fixed at 0.05:1 by weight, and the quantity of CNT/TiO2 loaded in
PVP solution varied between 30 and 60 % wt. CNT/TiO2 nanofibers have high
specific surface area (116 m2/g), significantly higher than that of TiO2
nanofibers (44 m2/g). The photocatalytic performance of the CNT/TiO2 nanofibers
was investigated by decolorization of 1 * 10-5 M methylene blue (MB) dye (in
water solution) and degradation of 100 ppm gaseous benzene under visible light
irradiation. The 50-CNT/TiO2 nanofibers (calcined CNT/TiO2 nanofibers fabricated
from a spinning solution of 50 % wt CNT/TiO2 based on PVP) had higher MB
degradation efficiency (58 %) than did other CNT/TiO2 nanofibers and pristine
TiO2 nanofibers (15 %) under visible light irradiation. The photocatalytic
degradation of gaseous benzene under visible light irradiation on filters made of
50-CNT/TiO2 nanofibers was carried out in a simulated air purifier system.
Similar to MB results, the degradation efficiency of gaseous benzene by 50
CNT/TiO2 nanofibers (52 %) was higher than by other CNT/TiO2 nanofibers and
pristine TiO2 nanofibers (18 %). The synergistic effects of the larger surface
area and lower band gap energy of CNT/TiO2 nanofibers were presented as strong
adsorption ability and greater visible light adsorption. The CNT/TiO2 nanofiber
prepared in this study has potential for use in air purifiers to improve air
treatment efficiency with less energy.
PMID- 27502567
TI - Use of mixed solid waste as a soil amendment for saline-sodic soil remediation
and oat seedling growth improvement.
AB - Soil salinization has become a worldwide problem that imposes restrictions on
crop production and food quality. This study utilizes a soil column experiment to
address the potential of using mixed solid waste (vinegar residue, fly ash, and
sewage sludge) as soil amendment to ameliorate saline-sodic soil and enhance crop
growth. Mixed solid waste with vinegar residue content ranging from 60-90 %,
sewage sludge of 8.7-30 %, and fly ash of 1.3-10 % was added to saline-sodic soil
(electrical conductivity (EC1:5) = 1.83 dS m-1, sodium adsorption ratio (SAR1:5)
= 129.3 (mmolc L-1)1/2, pH = 9.73) at rates of 0 (control), 130, 260, and 650 kg
ha-1. Results showed that the application of waste amendment significantly
reduced SAR, while increasing soil soluble K+, Ca2+, and Mg2+, at a dose of 650
kg ha-1. The wet stability of macro-aggregates (>1 mm) was improved 90.7-133.7 %
when the application rate of amendment was greater than 260 kg ha-1. The
application of this amendment significantly reduced soil pH. Germination rates
and plant heights of oats were improved with the increasing rate of application.
There was a positive correlation between the percentage of vinegar residue and
the K/Na ratio in the soil solutions and roots. These findings suggest that
applying a mixed waste amendment (vinegar residue, fly ash, and sewage sludge)
could be a cost-effective method for the reclamation of saline-sodic soil and the
improvement of the growth of salt-tolerant plants.
PMID- 27502568
TI - Biosynthesised magnetic iron nanoparticles for sludge dewatering via Fenton
process.
AB - The magnetic iron nanoparticles (MFeNp) were biosynthesised using the extract of
Cinnamomum tamala (bay leaf) and examined for its efficacy on sludge dewatering.
The characteristics of MFeNp were studied using scanning electron microscope
(SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD), Fourier
transform infrared spectroscopy (FTIR) and x-ray photoelectron spectrometer (XPS)
techniques. The presence of polyphenolic compounds were confirmed by FTIR and XPS
analysis. The reduction in capillary suction time (CST) (71.36 to 16.5 s) and
specific resistance to filtration (SRF) (53.71 * 1011 to 1.47 * 1011 m/kg) values
have indicated that the use of Fenton nanocatalyst enhanced the sludge
dewaterability. The differential scanning calorimetry (DSC) analysis has shown
that the mass of bound water in the treated sludge was decreased significantly
from 1.45 to 0.92 kg H2O/kg DS. The breakdown of extracellular polymeric
substances (EPS) by the MFeNp leads to the significant reduction in proteins,
polysaccharides, water content and heavy metals. The optimisation using response
surface modelling (RSM) have shown that the maximum removal efficiency of water
from the sludge was 85.9 % when the optimum pH (3) MFeNp dosage (50 mg/g DS) and
H2O2 dosage (500 mg/g DS) were maintained. The experimental results and the
statistical optimisation have suggested that MFeNp can be used as a potential
nanocatalyst for the sludge dewaterability and hence it can be used for the
agricultural purpose. Graphical abstract Schematic representation of sludge
dewatering process.
PMID- 27502569
TI - Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine
in human immune system mice.
AB - A number of studies have shown that CD8+ T cells mediate protective anti-malaria
immunity in a mouse model. However, whether human CD8+ T cells play a role in
protection against malaria remains unknown. We recently established human immune
system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by
transduction with HLA-A*0201 and certain human cytokines using recombinant adeno
associated virus-based gene transfer technologies. These HIS-CD8 mice mount a
potent, antigen-specific HLA-A*0201-restricted human CD8+ T-cell response upon
immunization with a recombinant adenovirus expressing a human malaria antigen,
the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In
the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic
Plasmodium berghei sporozoites expressing full-length PfCSP and found that
AdPfCSP-immunized (but not naive) mice were protected against subsequent malaria
challenge. The level of the HLA-A*0201-restricted, PfCSP-specific human CD8+ T
cell response was closely correlated with the level of malaria protection.
Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice
almost completely abolished the anti-malaria immune response. Taken together, our
data show that human CD8+ T cells mediate protective anti-malaria immunity in
vivo.
PMID- 27502571
TI - Radiative neutron capture as a counting technique at pulsed spallation neutron
sources: a review of current progress.
AB - Neutron scattering techniques are attracting an increasing interest from
scientists in various research fields, ranging from physics and chemistry to
biology and archaeometry. The success of these neutron scattering applications is
stimulated by the development of higher performance instrumentation. The
development of new techniques and concepts, including radiative capture based
neutron detection, is therefore a key issue to be addressed. Radiative capture
based neutron detectors utilize the emission of prompt gamma rays after neutron
absorption in a suitable isotope and the detection of those gammas by a photon
counter. They can be used as simple counters in the thermal region and
(simultaneously) as energy selector and counters for neutrons in the eV energy
region. Several years of extensive development have made eV neutron spectrometers
operating in the so-called resonance detector spectrometer (RDS) configuration
outperform their conventional counterparts. In fact, the VESUVIO spectrometer, a
flagship instrument at ISIS serving a continuous user programme for eV inelastic
neutron spectroscopy measurements, is operating in the RDS configuration since
2007. In this review, we discuss the physical mechanism underlying the RDS
configuration and the development of associated instrumentation. A few successful
neutron scattering experiments that utilize the radiative capture counting
techniques will be presented together with the potential of this technique for
thermal neutron diffraction measurements. We also outline possible improvements
and future perspectives for radiative capture based neutron detectors in neutron
scattering application at pulsed neutron sources.
PMID- 27502570
TI - Live-vaccinia virus encapsulation in pH-sensitive polymer increases safety of a
reservoir-targeted Lyme disease vaccine by targeting gastrointestinal release.
AB - The incidence of Lyme disease has continued to rise despite attempts to control
its spread. Vaccination of zoonotic reservoirs of human pathogens has been
successfully used to decrease the incidence of rabies in raccoons and foxes. We
have previously reported on the efficacy of a vaccinia virus vectored vaccine to
reduce carriage of Borrelia burgdorferi in reservoir mice and ticks. One
potential drawback to vaccinia virus vectored vaccines is the risk of accidental
infection of humans. To reduce this risk, we developed a process to encapsulate
vaccinia virus with a pH-sensitive polymer that inactivates the virus until it is
ingested and dissolved by stomach acids. We demonstrate that the vaccine is
inactive both in vitro and in vivo until it is released from the polymer. Once
released from the polymer by contact with an acidic pH solution, the virus
regains infectivity. Vaccination with coated vaccinia virus confers protection
against B. burgdorferi infection and reduction in acquisition of the pathogen by
naive feeding ticks.
PMID- 27502572
TI - Thymic E4bp4 gene transcription is up-regulated in the chicken during
experimental peritonitis modified by the season-related lighting conditions.
AB - Immunity, like other vertebrate processes, undergoes the diurnal and seasonal
rhythmicity generated and synchronized by the endogenous clock. In the present
study a transcription of the selected clock genes was evaluated in the chicken
thymus to verify its supposed role as a peripheral clock and to check its
relation with the seasonality of immune function. Chickens kept from hatch in the
season-related lighting conditions (LD 16:8 in summer vs 8:16 in winter) and in a
controlled temperature were exposed to the experimental peritonitis elicited by
i.p. thioglycollate injection. Previously described seasonality of the
inflammatory response has been confirmed and the diurnal rhythms of a core clock
gene Per3 and its repressor E4bp4 in the thymus has been evidenced. E4bp4
transcription was up-regulated in inflamed chickens while that of Per3 appeared
independent of the locally induced inflammation. Our results suggest an
interconnecting role of E4BP4 between molecular clock and immunity in the
chicken.
PMID- 27502573
TI - Application of diffusion-weighted imaging and dynamic susceptibility contrast
perfusion-weighted imaging for ganglioglioma in adults: Comparison study with
oligodendroglioma.
AB - BACKGROUND AND PURPOSE: To evaluate diffusion-weighted imaging (DWI) and dynamic
susceptibility contrast perfusion-weighted imaging (DSC-PWI) of ganglioglioma
(GG) compared with oligodendroglioma (ODG). MATERIALS AND METHODS: We enrolled 36
patients with histopathologically confirmed GG (12 patients) or ODG (24
patients). The volumetric analyses of normalized ADC (nADC) and normalized CBV
(nCBV) maps, tumor volume, and ratio of enhancing portion compared to the tumor
volume were performed. The microvessel area (MVA) was analyzed by staining with
the CD34 monoclonal antibody. RESULTS: GGs occurred more frequently in the
temporal lobe than in the frontal lobe. GGs showed a smaller tumor volume, and
higher ratio of enhancing portion per tumor volume than ODGs (P=.002, and P=.010,
respectively). GGs also showed lower nADC values (1.055+/-0.063 vs 1.204+/-0.030,
P=.021) and higher nCBV values (0.777+/-0.032 vs 0.514+/-0.025, P<.001) than
ODGs. Among the parameters in the multivariate model, nCBV was the most
significant factor for differentiating GGs and ODGs (P<.0001). GGs showed
significantly higher MVAs than ODGs (0.48+/-0.09 vs 0.24+/-0.04, P=.025).
CONCLUSION: Our results suggest that GGs tend to have relatively smaller tumor
volume with higher ratio of enhancing portions, lower nADC values, and higher
nCBV values than ODGs. Among these parameters, measurement of nCBV, which is
correlated with a higher MVA measurement in GGs, can be the most useful tool for
differentiating GGs from ODGs.
PMID- 27502574
TI - Tracking successive Wallerian degenerations in a relapsing-remitting multiple
sclerosis patient.
PMID- 27502575
TI - Role of intratumoral flow void signs in the differential diagnosis of
intracranial solitary fibrous tumors and meningiomas.
AB - BACKGROUND AND OBJECTIVE: An absence of signal on magnetic resonance (MR) images
caused by blood or cerebral spinal fluid flow is known as a flow void, and may be
related to intracranial tumors such as intracranial solitary fibrous tumor (SFT)
or meningioma. However, the differential diagnosis of these neoplasms based on
flow void configuration is controversial. This study investigated common
intratumoral flow void patterns for differentiating intracranial SFT from
meningioma. METHODS: From May 2008 to May 2015, 14 patients (10 men, 4 women; 14
63y) received a pathologic diagnosis of primary intracranial SFT, and in 85
patients (23 men, 62 women; 20-76y) a pathologic diagnosis of meningioma was
made. Intratumoral flow void signs were retrospectively observed on MR images of
all these patients and classified by radiologists blinded to the pathology
findings. Statistical significance was established by chi-squared tests. RESULTS:
In intracranial SFT patients, the sunburst flow void was detected in 1 case
(7.1%) and the serpentine in 13 cases (92.9%). In meningioma patients, the
sunburst flow void was detected in 82 cases (96.5%) and the serpentine in 3 cases
(3.5%). The differences in the prevalence of the flow void types between the 2
groups were significant (chi(2)=64.348; P<0.01). CONCLUSION: Intracranial SFTs on
MR images were more likely to show a serpentine than a sunburst flow void, while
the sunburst pattern was far more typical of meningioma. Thus, the pattern of the
intratumoral flow void sign may be a useful tool to assist in differentiating
these tumors.
PMID- 27502576
TI - Endovascular treatment of intracranial aneurysms with Barricade coils:
Feasibility, procedural safety, and immediate postoperative anatomical results.
AB - BACKGROUND AND PURPOSE: The safety of bare platinum coils has been widely
described in the literature. This study aimed to report the first series of
intracranial aneurysms treated with Barricade bare platinum coils with a
comprehensive evaluation of their procedural safety and postprocedural anatomical
results. METHODS: Patients with intracranial aneurysms treated between October
2013 and December 2015 by simple coiling or balloon-assisted coiling with
Barricade coils (Blockade Medical, Irvine, California, USA) were prospectively
included in a database and retrospectively studied. For all included patients,
the patient and aneurysm characteristics, procedural complications, technical
issues, postoperative anatomical results, and one-month clinical outcome
(modified Rankin Scale) were evaluated by an independent interventional
neuroradiologist. RESULTS: Eighty-eight patients harboring 97 aneurysms were
included. Procedural complications and technical issues were encountered in 17
and 5 patients (19.3 and 5.7%, respectively), but clinical worsening in only 2
patients (2.2%). There was no treatment-related mortality. After one month,
morbidity (mRS>=1) was observed in 19 patients (21.8%), 17 related to
subarachnoid hemorrhage (SAH) in patients with ruptured aneurysms (19.4%) and 2
related to thromboembolic events in patients with unruptured aneurysms (2.3%).
Nine patients initially presenting with a ruptured aneurysm were deceased at 1
month as a consequence of SAH (10.2%). Adequate occlusion was observed
postoperatively in 94.8% of the aneurysms (complete occlusion in 81.4% and
residual neck in 13.4%). CONCLUSION: Endovascular treatment of intracranial
aneurysms with Barricade coils is feasible and the demonstrated overall safety
results are within the ranges found in the literature for other coils. Immediate
anatomical results are satisfying.
PMID- 27502577
TI - Serum amyloid A1 is induced by UV irradiation and detected by toll-like receptor
4 to causes skin inflammation.
PMID- 27502579
TI - Clinical and subjective evaluation of implants in patients with hypodontia: a two
year observation study.
AB - BACKGROUND: Hypodontia compromises appearance and function and is challenging to
manage clinically. OBJECTIVES: To assess the impact of implant retained crowns on
quality of life of patients and to determine clinical performance of implant
retained crowns in these patients. METHODS: In a 24-month prospective observation
study, patients with non-syndromic mild hypodontia manifested with missing teeth
in the anterior maxilla were included. Pre-treatment screening included a
clinical and radiographic examination and completion of an OHIP-20. Narrow neck
SLActive TiZr implants (Roxolid(r) , Straumann AG, Switzerland) were provided and
restored with single unit crowns. Implant stability was recorded at time of
placement and abutment connection. Standardized radiographs were recorded at time
of surgery, abutment connection and 12- and 24-month follow-up visits, and
distance between implant shoulder and first bone contact was measured. Oral
health-related quality of life was calculated using OHIP-20 scores at 12- and 24
month visits compared with pre-treatment scores. Pink (PES) and white (WES)
aesthetic scores were used to objectively assess aesthetic outcome of treatment.
RESULTS: Twenty implants were placed in 12 patients (seven females, five males;
mean [SD] age 19.33 [2.37] years). There was a significant improvement in oral
health-related quality of life following treatment (P = 0.026), and the effect
size of this change was 1.17 indicating a large clinically meaningful change.
Mean PES and WES scores were high, indicated a satisfactory aesthetic outcome at
24 months. Crestal bone-level changes were considered small. CONCLUSION:
Favourable clinical outcomes were observed. Implant retained crowns had a large
and clinically meaningful impact on quality of life of patients with hypodontia.
PMID- 27502578
TI - Bisphenol A Exposure May Induce Hepatic Lipid Accumulation via Reprogramming the
DNA Methylation Patterns of Genes Involved in Lipid Metabolism.
AB - Accumulating evidence suggests a role of bisphenol A (BPA) in metabolic
disorders. However, the underlying mechanism is still unclear. Using a mouse BPA
exposure model, we investigated the effects of long-term BPA exposure on lipid
metabolism and the underlying mechanisms. The male mice exposed to BPA (0.5 MUg
BPA /kg/day, a human relevant dose) for 10 months exhibited significant hepatic
accumulation of triglycerides and cholesterol. The liver cells from the BPA
exposed mice showed significantly increased expression levels of the genes
related to lipid synthesis. These liver cells showed decreased DNA methylation
levels of Srebf1 and Srebf2, and increased expression levels of Srebf1 and Srebf2
that may upregulate the genes related to lipid synthesis. The expression levels
of DNA methyltransferases were decreased in BPA-exposed mouse liver. Hepa1-6 cell
line treated with BPA showed decreased expression levels of DNA
methyltransferases and increased expression levels of genes involved in lipid
synthesis. DNA methyltransferase knockdown in Hepa1-6 led to hypo-methylation and
increased expression levels of genes involved in lipid synthesis. Our results
suggest that long-term BPA exposure could induce hepatic lipid accumulation,
which may be due to the epigenetic reprogramming of the genes involved in lipid
metabolism, such as the alterations of DNA methylation patterns.
PMID- 27502580
TI - Extremely heat tolerant photo-symbiosis in a shallow marine benthic foraminifera.
AB - Bleaching, the loss of algal symbionts, occurs in marine photosymbiotic organisms
at water temperatures minimally exceeding average summer SST (sea surface
temperatures). Pre-adaptation allows organisms to persist under warmer
conditions, providing the tolerance can be carried to new habitats. Here we
provide evidence for the existence of such adaptation in the benthic foraminifera
Pararotalia calcariformata. This species occurs at a thermally polluted site in
the Mediterranean, where water temperatures reach a maxima daily average of 36
degrees C during the summer. To test whether this occurrence represents a
widespread adaptation, we conducted manipulative experiments exposing this
species from an unpolluted site to elevated temperatures (20-42 degrees C). It
was kept in co-culture with the more thermally sensitive foraminifera
Amphistegina lobifera in two experiments (20-36 degrees C). Reduced
photosynthetic activity in A. lobifera occurred at 32 degrees C whereas
photochemical stress in P. calcariformata was first observed during exposure to
36 degrees C. Pararotalia calcariformata survived all treatment conditions and
grew under 36 degrees C. The photosymbiosis in P. calcariformata is unusually
thermally tolerant. These observations imply that marine eukaryote-eukaryote
photosymbiosis can respond to elevated temperatures by drawing on a pool of
naturally occurring pre-adaptations. It also provides a perspective on the
massive occurrence of symbiont-bearing foraminifera in the early Cenozoic
hothouse climate.
PMID- 27502581
TI - Prognostic factors for long-term infliximab treatment in Crohn's disease
patients: a 20-year single centre experience.
AB - BACKGROUND: The long-term efficacy of infliximab in patients with Crohn's disease
is suboptimal. AIM: To study prognostic factors for real-life long-term effcacy
of infliximab in Crohn's disease. METHODS: All consecutive Crohn's disease
patients treated with infliximab at a tertiary centre were retrospectively
analysed. Only patients who received scheduled infliximab maintenance treatment
were considered. Patient- and disease-related factors were used to identify
independent predictors of infliximab failure-free survival using Cox proportional
hazards regression. RESULTS: Of 1031 patients with Crohn's disease, 261 were
eligible for inclusion. Median time on infliximab was 2.4 [IQR 1.4-4.7] years,
and 65 (24.9%) patients experienced infliximab failure. Estimated 5-year
infliximab failure-free survival was 65.9% (95% CI 58.3-73.5). Multivariate Cox
regression identified disease duration >=1 year (HR 2.5 (95% CI 1.2-5.2), P =
0.02), L1 disease location [HR 2.0 (1.1-3.5), P = 0.02], prior anti-TNF use [HR
2.3 (1.1-4.8), P = 0.03], haemoglobin <13.5 g/dL [HR 2.3 (1.2-4.4), P = 0.02],
not using therapeutic drug monitoring [HR 8.0 (4.1-15.6), P = 1 * 10(-9) ], and
first dose optimisation within first year [HR 3.7 (2.1-6.6), P = 5 * 10(-6) ] as
independent predictors of infliximab failure-free survival. Stratifying patients
into risk groups resulted in estimated 3-year infliximab failure-free survival
rates ranging from 95.3% (94.2-96.4) to 26.3% (8.6-44.0) depending on the number
of risk factors (P = 8 * 10(-13) ). CONCLUSIONS: This study identified several
easy to obtain predictors of infliximab failure in patients with Crohn's disease,
and these are in line with previous reports. Those with a high-risk profile for
infliximab failure in whom infliximab initiation is considered, should be treated
as early as possible making use of therapeutic drug monitoring.
PMID- 27502582
TI - Evaluation of two doses of etoricoxib, a COX-2 selective non-steroidal anti
inflammatory drug (NSAID), in the treatment of Rheumatoid Arthritis in a double
blind, randomized controlled trial.
AB - BACKGROUND: Treatment with non-steroidal anti-inflammatory drugs (NSAID) is a
common component of treatment regimens for rheumatoid arthritis (RA). Etoricoxib
is a COX-2 selective NSAID that has demonstrated efficacy in the treatment of RA
at a dose of 90 mg. The current study further evaluated the efficacy of
etoricoxib 60 mg and 90 mg in RA patients with active disease. METHODS: This was
a 2-part, double-blind, placebo-controlled study in RA (NCT01208181). Patients
were required to have a diagnosis of RA (according to ARA 1987 revised
classification criteria) and were to demonstrate symptom flare upon
discontinuation of previous NSAID treatment prior to randomization. Part I was a
6-week, placebo-controlled period to assess the efficacy of etoricoxib 90 mg and
etoricoxib 60 mg, each compared to placebo, as well as to each other. Part II was
a 6-week period to evaluate the potential benefit of dose escalation from
etoricoxib 60 mg to etoricoxib 90 mg after 6 weeks exposure to etoricoxib 60 mg
in Part I compared to maintaining a steady dose of etoricoxib 60 mg throughout
Parts I and II. Primary endpoints were Disease Activity Score evaluating 28
joints and C reactive protein level (DAS28-CRP) index and Patient Global
Assessment of Pain (Pain) score (0-100 mm VAS) after 6 weeks of treatment in Part
I. Adverse events were monitored throughout the study. RESULTS: In total, 1404
patients were randomized in a 2:7:7:8 ratio; 1228 patients completed Part I and
713 patients continued to Part II. Both etoricoxib doses were superior to placebo
on both primary efficacy endpoints (p = 0.004 for 60 mg and p = 0.034 for 90 mg
for DAS28-CRP; p < 0.001 for both doses for PGAP) in Part I. Further in Part I,
etoricoxib 90 mg was not significantly different from 60 mg for DAS28-CRP, but
did demonstrate a small, but statistically significant decrease in baseline PGAP
score vs. 60 mg (p = 0.019). In Part II, there was no significant decrease in
PGAP score after increasing to 90 mg in subjects with inadequate pain relief on
60 mg as compared to subjects who stayed on 60 mg. The incidence of AEs and SAEs
were similar between etoricoxib 60 mg and 90 mg in both Part I and II.
CONCLUSION: Both etoricoxib 90 mg and 60 mg are superior to placebo in relieving
the symptoms of RA. Etoricoxib 90 mg vs 60 mg resulted in a statistically
significant, though small, improvement in PGAP score, but not DAS28-CRP. Dose
escalation from 60 mg to 90 mg in pain inadequate responders did not
significantly improve efficacy. These results confirm the efficacy and
tolerability of etoricoxib 90mg in patients with RA. In addition, this study
demonstrated that etoricoxib 60 mg is also efficacious and well-tolerated in RA.
CLINICAL TRIAL REGISTRATION: NCT01208181 (registered September 22, 2010).
PMID- 27502583
TI - Long-Term Effects of an Internet-Mediated Pedometer-Based Walking Program for
Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.
AB - BACKGROUND: Regular physical activity (PA) is recommended for persons with
chronic obstructive pulmonary disease (COPD). Interventions that promote PA and
sustain long-term adherence to PA are needed. OBJECTIVE: We examined the effects
of an Internet-mediated, pedometer-based walking intervention, called Taking
Healthy Steps, at 12 months. METHODS: Veterans with COPD (N=239) were randomized
in a 2:1 ratio to the intervention or wait-list control. During the first 4
months, participants in the intervention group were instructed to wear the
pedometer every day, upload daily step counts at least once a week, and were
provided access to a website with four key components: individualized goal
setting, iterative feedback, educational and motivational content, and an online
community forum. The subsequent 8-month maintenance phase was the same except
that participants no longer received new educational content. Participants
randomized to the wait-list control group were instructed to wear the pedometer,
but they did not receive step-count goals or instructions to increase PA. The
primary outcome was health-related quality of life (HRQL) assessed by the St
George's Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome
was daily step count. Linear mixed-effect models assessed the effect of
intervention over time. One participant was excluded from the analysis because he
was an outlier. Within the intervention group, we assessed pedometer adherence
and website engagement by examining percent of days with valid step-count data,
number of log-ins to the website each month, use of the online community forum,
and responses to a structured survey. RESULTS: Participants were 93.7% male
(223/238) with a mean age of 67 (SD 9) years. At 12 months, there were no
significant between-group differences in SGRQ-TS or daily step count. Between
group difference in daily step count was maximal and statistically significant at
month 4 (P<.001), but approached zero in months 8-12. Within the intervention
group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which
decreased over the months of study (P<.001). Mean number of log-ins to the
website each month also significantly decreased over the months of study
(P<.001). The online community forum was used at least once during the study by
83.8% (129/154) of participants. Responses to questions assessing participants'
goal commitment and intervention engagement were not significantly different at
12 months compared to 4 months. CONCLUSIONS: An Internet-mediated, pedometer
based PA intervention, although efficacious at 4 months, does not maintain
improvements in HRQL and daily step counts at 12 months. Waning pedometer
adherence and website engagement by the intervention group were observed. Future
efforts should focus on improving features of PA interventions to promote long
term behavior change and sustain engagement in PA. CLINICALTRIAL:
Clinicaltrials.gov NCT01102777; https://clinicaltrials.gov/ct2/show/NCT01102777
(Archived by WebCite at http://www.webcitation.org/6iyNP9KUC).
PMID- 27502585
TI - Using AberOWL for fast and scalable reasoning over BioPortal ontologies.
AB - BACKGROUND: Reasoning over biomedical ontologies using their OWL semantics has
traditionally been a challenging task due to the high theoretical complexity of
OWL-based automated reasoning. As a consequence, ontology repositories, as well
as most other tools utilizing ontologies, either provide access to ontologies
without use of automated reasoning, or limit the number of ontologies for which
automated reasoning-based access is provided. METHODS: We apply the AberOWL
infrastructure to provide automated reasoning-based access to all accessible and
consistent ontologies in BioPortal (368 ontologies). We perform an extensive
performance evaluation to determine query times, both for queries of different
complexity and for queries that are performed in parallel over the ontologies.
RESULTS AND CONCLUSIONS: We demonstrate that, with the exception of a few
ontologies, even complex and parallel queries can now be answered in
milliseconds, therefore allowing automated reasoning to be used on a large scale,
to run in parallel, and with rapid response times.
PMID- 27502584
TI - MicroRNA-203 mimics age-related aortic smooth muscle dysfunction of cytoskeletal
pathways.
AB - Increased aortic stiffness is a biomarker for subsequent adverse cardiovascular
events. We have previously reported that vascular smooth muscle Src-dependent
cytoskeletal remodelling, which contributes to aortic plasticity, is impaired
with ageing. Here, we use a multi-scale approach to determine the molecular
mechanisms behind defective Src-dependent signalling in an aged C57BL/6 male
mouse model. Increased aortic stiffness, as measured in vivo by pulse wave
velocity, was found to have a comparable time course to that in humans.
Bioinformatic analyses predicted several miRs to regulate Src-dependent
cytoskeletal remodelling. qRT-PCR was used to determine the relative levels of
predicted miRs in aortas and, notably, the expression of miR-203 increased almost
twofold in aged aorta. Increased miR-203 expression was associated with a
decrease in both mRNA and protein expression of Src, caveolin-1 and paxillin in
aged aorta. Probing with phospho-specific antibodies confirmed that
overexpression of miR-203 significantly attenuated Src and extracellular signal
regulated kinase (ERK) signalling, which we have previously found to regulate
vascular smooth muscle stiffness. In addition, transfection of miR-203 into
aortic tissue from young mice increased phenylephrine-induced aortic stiffness ex
vivo, mimicking the aged phenotype. Upstream of miR-203, we found that DNA
methyltransferases (DNMT) 1, 3a, and 3b are also significantly decreased in the
aged mouse aorta and that DNMT inhibition significantly increases miR-203
expression. Thus, the age-induced increase in miR-203 may be caused by epigenetic
promoter hypomethylation in the aorta. These findings indicate that miR-203
promotes a re-programming of Src/ERK signalling pathways in vascular smooth
muscle, impairing the regulation of stiffness in aged aorta.
PMID- 27502586
TI - EFFECTS: an expanded access program of everolimus for patients with subependymal
giant cell astrocytoma associated with tuberous sclerosis complex.
AB - BACKGROUND: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, has
been shown to be effective and safe in the treatment of subependymal giant cell
astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC). The
Everolimus For Fast Expanded aCcess in TSC SEGA (EFFECTS) study was designed to
provide everolimus access to patients with SEGA associated with TSC and to mainly
assess the safety and also efficacy of everolimus in a real-world setting.
METHODS: EFFECTS was a phase 3b, open-label, noncomparative, multicenter,
expanded access study. Eligible patients were >= 3 years of age, with a definite
diagnosis of TSC, and with at least one SEGA lesion identified by MRI or CT scan.
Patients received once daily everolimus (dose adjusted to attain a trough level
of 5-15 ng/mL). Safety evaluation was the primary objective and included
collection of adverse events (AEs) and serious AEs, with their severity and
relationship to everolimus. Efficacy evaluation, which was the secondary
objective, was based on the best overall response as per medical judgment.
RESULTS: Of the 120 patients enrolled, 100 (83.3%) completed the study. Median
age of patients was 11 years (range, 1-47). Median daily dose of everolimus was
5.82 mg (range, 2.0-11.8). Median duration of exposure was 56.5 weeks (range, 0.3
130). The overall incidence of AEs was 74.2%. Aphthous stomatitis (18 [15.0%]),
pyrexia (18 [15.0%]), bronchitis (11 [9.2%]), and stomatitis (10 [8.3%]) were the
most common AEs reported. Overall, 25 patients had grade 3 AEs; most frequent was
stomatitis (4 [3.3%]). Grade 4 AEs were reported in three (2.5%) patients. A
total of 62 (51.7%) patients had suspected drug-related AEs, of which 15 (12.5%)
were of grade 3 or 4. In eight (6.7%) patients, AEs led to drug discontinuation.
With regard to efficacy, 81 (67.5%) patients had a partial response, 35 (29.2%)
had a stable disease, and one (0.8%) had progressive disease. The response was
unknown in three (2.5%) patients. CONCLUSION: This study confirms the acceptable
safety profile of everolimus in patients with SEGA associated with TSC in a real
world setting. The results further support the efficacy of everolimus in the
treatment of SEGA associated with TSC. (EudraCT: 2010-022583-13).
PMID- 27502587
TI - Copper induces hepatocyte injury due to the endoplasmic reticulum stress in
cultured cells and patients with Wilson disease.
AB - Copper is an essential trace element, however, excess copper is harmful to human
health. Excess copper-derived oxidants contribute to the progression of Wilson
disease, and oxidative stress induces accumulation of abnormal proteins. It is
known that the endoplasmic reticulum (ER) plays an important role in proper
protein folding, and that accumulation of misfolded proteins disturbs ER
homeostasis resulting in ER stress. However, copper-induced ER homeostasis
disturbance has not been fully clarified. We treated human hepatoma cell line
(Huh7) and immortalized-human hepatocyte cell line (OUMS29) with copper and
chemical chaperones, including 4-phenylbutyrate and ursodeoxycholic acid. We
examined copper-induced oxidative stress, ER stress and apoptosis by
immunofluorescence microscopy and immunoblot analyses. Furthermore, we examined
the effects of copper on carcinogenesis. Excess copper induced not only oxidative
stress but also ER stress. Furthermore, excess copper induced DNA damage and
reduced cell proliferation. Chemical chaperones reduced this copper-induced
hepatotoxicity. Excess copper induced hepatotoxicity via ER stress. We also
confirmed the abnormality of ultra-structure of the ER of hepatocytes in patients
with Wilson disease. These findings show that ER stress plays a pivotal role in
Wilson disease, and suggests that chemical chaperones may have beneficial effects
in the treatment of Wilson disease.
PMID- 27502588
TI - Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle
cells involved in the modulation of calcium sensing receptor in high
homocysteine.
AB - Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells
(VSMCs). Hydrogen sulfide (H2S) inhibits the phenotype switch of VSMCs and
calcium-sensing receptor (CaSR) regulated the production of endogenous H2S.
However, whether CaSR inhibits the proliferation of VSMCs by regulating the
endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S)
pathway in high homocysteine (HHcy) has not been previously investigated. The
intracellular calcium concentration, the concentration of H2S, the cell
viability, the proliferation and the expression of proteins of cultured VSMCs
from rat thoracic aortas were measured, respectively. The results showed that the
[Ca(2+)]i and the expression of p-CaMK and CSE increased upon treatment with CaSR
agonist. In HHcy, the H2S concentration decrease, the proliferation and migration
rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2
increased while the alpha-SM actin, P21(Cip/WAK-1) and Calponin decreased. The
CaSR agonist or exogenous H2S significantly reversed the changes of VSMCs caused
by HHcy. In conclusion, our results demonstrated that CaSR regulate the
endogenous CSE/H2S is related to the PLC-IP3 receptor and CaM signal pathways
which inhibit the proliferation of VSMCs, and the latter is involved in the
Erk1/2 dependent signal pathway in high homocysteine.
PMID- 27502589
TI - ACEMg-mediated hearing preservation in cochlear implant patients receiving
different electrode lengths (PROHEARING): study protocol for a randomized
controlled trial.
AB - BACKGROUND: The indications for a cochlear implant (CI) have been extended to
include patients with some residual hearing. Shorter and thinner atraumatic
electrodes have been designed to preserve the residual hearing in the implanted
ear. However, the insertion of the electrode array into the cochlea, with
potential mechanical trauma and the presence of this foreign body inside the
cochlea, may lead to free radical formation and reduced blood perfusion of the
cochlea which can result in the loss of residual hearing. METHODS/DESIGN: In this
single-center, randomized, placebo-controlled, double-blind phase II clinical
trial the effect of free radical scavengers and a vasodilator on the residual
hearing of 140 CI patients will be evaluated. The formulation is composed of beta
carotene (vitamin A), ascorbic acid (vitamin C), dl-alpha-tocopherol acetate
(vitamin E) and the vasodilator magnesium (Mg), or ACEMg. Medication is
administered twice daily per os for approximately 3 months. The primary measure
is based upon the reduction in postoperative low-frequency air-conducted pure
tone thresholds compared to preoperative thresholds in ACEMg-treated patients
compared to those of a placebo group. Additionally, the effect of different
electrode lengths (20, 24 and 28 mm) is analyzed. Study visits are scheduled 2
days before surgery, at first fitting, which is the adjustment and start of
stimulation via CI 4 weeks after surgery and 3, 6, 9 and 12 months after first
fitting. The primary endpoint is the air-conduction hearing loss at 500 Hz 3
months after first fitting. Additionally, speech recognition tests, hearing aid
benefit in the implanted ear and electrophysiological measurements of implant
function are assessed. Since this is a blinded clinical trial and recruitment is
still ongoing, data continue to accrue and we cannot yet analyze the outcome of
the ACEMg treatment. DISCUSSION: There is an unfulfilled need for new strategies
to preserve acoustic hearing in CI patients. This study will provide first-in-man
data on ACEMg-mediated protection of residual hearing in CI patients. Performing
all surgeries and patient follow-up at one study site improves consistency in
diagnosis and therapy and less variability in surgery, audiological test
techniques and fitting. This approach will allow investigation of the influence
of ACEMg on residual hearing in CI patients. TRIAL REGISTRATION: The German
Bundesinstitut fur Arzneimittel und Medizinprodukte (BfArM) application number
4039192, was registered on 6 December 2013 with protocol amendment version 3.0
from 19 August 2014. EudraCT number: 2012-005002-22 .
PMID- 27502590
TI - Using the Theoretical Domains Framework (TDF) to understand adherence to multiple
evidence-based indicators in primary care: a qualitative study.
AB - BACKGROUND: There are recognised gaps between evidence and practice in general
practice, a setting posing particular implementation challenges. We earlier
screened clinical guideline recommendations to derive a set of 'high-impact'
indicators based upon criteria including potential for significant patient
benefit, scope for improved practice and amenability to measurement using
routinely collected data. Here, we explore health professionals' perceived
determinants of adherence to these indicators, examining the degree to which
determinants were indicator-specific or potentially generalisable across
indicators. METHODS: We interviewed 60 general practitioners, practice nurses and
practice managers in West Yorkshire, the UK, about adherence to four indicators:
avoidance of risky prescribing; treatment targets in type 2 diabetes; blood
pressure targets in treated hypertension; and anticoagulation in atrial
fibrillation. Interview questions drew upon the Theoretical Domains Framework
(TDF). Data were analysed using framework analysis. RESULTS: Professional role
and identity and environmental context and resources featured prominently across
all indicators whilst the importance of other domains, for example, beliefs about
consequences, social influences and knowledge varied across indicators. We
identified five meta-themes representing more general organisational and
contextual factors common to all indicators. CONCLUSIONS: The TDF helped elicit a
wide range of reported determinants of adherence to 'high-impact' indicators in
primary care. It was more difficult to pinpoint which determinants, if targeted
by an implementation strategy, would maximise change. The meta-themes broadly
underline the need to align the design of interventions targeting general
practices with higher level supports and broader contextual considerations.
However, our findings suggest that it is feasible to develop interventions to
promote the uptake of different evidence-based indicators which share common
features whilst also including content-specific adaptations.
PMID- 27502592
TI - Facial movement disorder and dopamine imaging in a patient with amphetamine
abuse.
PMID- 27502593
TI - Switching the poles in sexual and reproductive health research: implementing a
research capacity-strengthening network in West and North Africa.
AB - Health research capacities have been improved in Africa but still remain weak as
compared to other regions of the World. To strengthen these research capacities,
international collaboration and networking for knowledge and capacity transfer
are needed. In this commentary, we present the Network for Scientific Support in
the field of Sexual and Reproductive Health in West and North Africa, its
priority research topics and discuss its implementation process. Established in
January 2014, the Network aims at generating human rights and gender-based
research fully carried out and driven by South based institutions. It is composed
of 12 institutions including the Institute of Tropical Medicine of Antwerp
(Belgium) and 11 institutions from eight Francophone West and North African
countries. The key areas of interest of this network are health policies analysis
and health system research in family planning, HIV prevention among vulnerable
groups, quality of care and breast cancers. Since it started, seventeen research
proposals based on locally relevant research questions have been developed. Among
the seventeen proposals, eleven have been implemented. Several research
institutions enhanced linkages with local representations of international
partners such as UNFPA. The network is committed to strengthening methodological
research capacities and soft skills such as fundraising, advocacy and leadership.
Such competencies are strongly needed for developing an effective South-based
leadership in Sexual and Reproductive Health research, and for achieving the
Sustainable Development Goals.
PMID- 27502591
TI - Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of
Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice
Guideline.
AB - PURPOSE: To provide guidance to clinicians regarding the use of neoadjuvant
chemotherapy and interval cytoreduction among women with stage IIIC or IV
epithelial ovarian cancer. METHODS: The Society of Gynecologic Oncology and the
American Society of Clinical Oncology convened an Expert Panel and conducted a
systematic review of the literature. RESULTS: Four phase III clinical trials form
the primary evidence base for the recommendations. The published studies suggest
that for selected women with stage IIIC or IV epithelial ovarian cancer,
neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary
cytoreduction and adjuvant chemotherapy with respect to overall and progression
free survival and are associated with less perioperative morbidity and mortality.
RECOMMENDATIONS: All women with suspected stage IIIC or IV invasive epithelial
ovarian cancer should be evaluated by a gynecologic oncologist prior to
initiation of therapy. The primary clinical evaluation should include a CT of the
abdomen and pelvis, and chest imaging (CT preferred). Women with a high
perioperative risk profile or a low likelihood of achieving cytoreduction to < 1
cm of residual disease (ideally to no visible disease) should receive neoadjuvant
chemotherapy. Women who are fit for primary cytoreductive surgery, and with
potentially resectable disease, may receive either neoadjuvant chemotherapy or
primary cytoreductive surgery. However, primary cytoreductive surgery is
preferred if there is a high likelihood of achieving cytoreduction to < 1 cm
(ideally to no visible disease) with acceptable morbidity. Before neoadjuvant
chemotherapy is delivered, all patients should have confirmation of an invasive
ovarian, fallopian tube, or peritoneal cancer. Additional information is
available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.
PMID- 27502594
TI - Significance of EZH2 expression in canine mammary tumors.
AB - BACKGROUND: Current studies report that aberrations in epigenetic regulators or
chromatin modifications are related to tumor development and maintenance. EZH2
(Enhancer of zeste homolog 2) is one of the catalytic subunits of Polycomb
repressive complex 2, a crucial epigenetic regulator. EZH2 has a master
regulatory function in such processes as cell proliferation, stem cell
differentiation, and early embryogenesis. In humans, EZH2 is linked to oncogenic
function in several carcinomas, including breast cancer, and dysregulation of
EZH2 has been particularly associated with loss of differentiation and the
development of poorly differentiated breast cancer. In our present study, we were
interested in determining whether EZH2 is increased in canine mammary tumors,
which show similarities to human breast cancer. RESULTS: Investigation of the
expression of EZH2 in canine mammary tumors revealed that EZH2 protein was
overexpressed in canine mammary carcinomas, as in human breast cancer. In
addition, the immunohistochemical expression level of EZH2 was associated with
the degree of malignancy in canine mammary carcinoma. This is the first report to
describe EZH2 expression in canine mammary tumors. CONCLUSIONS: Because the
expression of EZH2 was similar in canine mammary carcinoma and human breast
cancer, spontaneous canine mammary tumors may be a suitable model for studying
EZH2 and treatment development.
PMID- 27502595
TI - Cryptosporidium parvum rhomboid1 has an activity in microneme protein CpGP900
cleavage.
AB - BACKGROUND: Apicomplexan parasites actively release transmembrane (TM) adhesive
proteins involved in host cell attachment and invasion. Rhomboids, a family of
intramembrane serine proteases, cleave these secreted adhesive proteins within
their TM domains as an essential step in completing the invasion process. In
Cryptosporidium parvum, the activity of rhomboids in cleaving microneme proteins
(MICs) has not been reported. In the present study, the interaction between C.
parvum rhomboids (CpROM1 and CpROM4) and C. parvum microneme proteins (CpGP900
and CpTRAP-C1) was investigated using yeast two-hybrid assay and co
immunoprecipitation assays. RESULTS: Our study demonstrated that CpROM1 protein
could interact with CpGP900 protein in co-transformed AH109 yeasts. Analysis of
these proteins in co-transfected mammalian cells showed that the cleavage product
of the CpGP900 protein was detected in the co-transfected cells. As control,
CpGP900 only was transfected into cells and no cleavage was observed. The results
suggested that CpGP900 protein was the substrate of CpROM1. Moreover, CpROM1 and
CpROM4 could not cleave CpTRAP-C1 protein, which is the substrate of T. gondii
rhomboid 2. CONCLUSIONS: Our results showed that CpROM1 is an active protease
that is involved in microneme protein CpGP900 cleavage, which lay the foundation
for further research on the mechanisms of C. parvum invasion.
PMID- 27502596
TI - The development of an automatically produced cholangiography procedure using the
reconstruction of portal-phase multidetector-row computed tomography images:
preliminary experience.
AB - PURPOSE: Fusion angiography using reconstructed multidetector-row computed
tomography (MDCT) images, and cholangiography using reconstructed images from
MDCT with a cholangiographic agent include an anatomical gap due to the different
periods of MDCT scanning. To conquer such gaps, we attempted to develop a
cholangiography procedure that automatically reconstructs a cholangiogram from
portal-phase MDCT images. METHODS: The automatically produced cholangiography
procedure utilized an original software program that was developed by the
Graduate School of Information Science, Nagoya University. This program
structured 5 candidate biliary tracts, and automatically selected one as the
candidate for cholangiography. The clinical value of the automatically produced
cholangiography procedure was estimated based on a comparison with manually
produced cholangiography. RESULTS: Automatically produced cholangiograms were
reconstructed for 20 patients who underwent MDCT scanning before biliary drainage
for distal biliary obstruction. The procedure showed the ability to extract the 5
main biliary branches and the 21 subsegmental biliary branches in 55 and 25 % of
the cases, respectively. The extent of aberrant connections and aberrant
extractions outside the biliary tract was acceptable. Among all of the
cholangiograms, 5 were clinically applied with no correction, 8 were applied with
modest improvements, and 3 produced a correct cholangiography before automatic
selection. CONCLUSIONS: Although our procedure requires further improvement based
on the analysis of additional patient data, it may represent an alternative to
direct cholangiography in the future.
PMID- 27502597
TI - Severe tricuspid regurgitation after mitral valve surgery: the risk factors and
results of the aggressive application of prophylactic tricuspid valve repair.
AB - PURPOSE: This study aimed to examine the risk factors for severe postoperative
tricuspid regurgitation (TR) in patients undergoing mitral valve surgery. We also
studied the effects of prophylactic tricuspid valve repair (TVR) on severe
postoperative TR. METHODS: We retrospectively studied 125 patients without severe
TR who underwent mitral valve surgery from 1987 to 2006. Patients did not undergo
TVR before 1998 (the early period, n = 54). In 1998 (the late period, n = 71),
patients with a preoperative tricuspid annular diameter of >=35 mm underwent TVR
using an annuloplasty ring (n = 52). RESULTS: In the analysis of the early
period, the rates of freedom from severe TR at 10 and 20 years after surgery were
76 and 59 %, respectively. A multivariate analysis identified moderate
preoperative TR as a significant risk factor for severe TR. In the late period,
none of the 52 patients who underwent TVR developed severe TR. However, 4/19
patients who did not undergo TVR developed severe TR, and all of these four
patients had a preoperative tricuspid annular diameter of <=35 mm. CONCLUSIONS:
Moderate preoperative TR is a significant risk factor for severe postoperative TR
in patients undergoing mitral valve surgery. The aggressive application of TVR
can prevent severe postoperative TR; however, tricuspid annular dilatation might
not be a good indicator for TVR.
PMID- 27502598
TI - Clinical factors that affect the outcomes after anatomical versus non-anatomical
resection for hepatocellular carcinoma.
AB - PURPOSE: For hepatocellular carcinoma (HCC), the superiority of anatomical
resection (AR) over non-anatomical resection (NR) is still controversial. In this
study, we assessed the potential benefits of AR for HCC. METHODS: We enrolled 173
consecutive patients with HCC who underwent hepatectomy in our hospital from
August 2003 to May 2013 and compared the outcomes for the AR group (n = 125) with
those for the NR group (n = 48). RESULTS: The median observational period was 790
days. The 1- and 2-year overall survival (OS) rates were 92.1 and 85.8 %,
respectively; the 1- and 2-year disease-free survival (DFS) rates were 78.2 and
63.0 %, respectively. The AR and NR groups did not significantly differ in the OS
or DFS. However, the 2-year DFS was significantly better for the AR group than
the NR group among HCV patients (68.2 vs. 32.2 %; P = 0.004) and patients with
alpha-fetoprotein (AFP) within the normal range (<20 ng/ml; 76.7 vs. 60.9 %; P =
0.031), total bilirubin <0.8 mg/dl (70.8 vs. 47.0 %; P = 0.034), and tumors 2-5
cm in diameter (82.0 vs. 62.5 %; P = 0.025). CONCLUSIONS: If a patient is HCV
negative, has low AFP, low total bilirubin, or a tumor diameter of 2-5 cm, AR is
recommended.
PMID- 27502599
TI - Risk factors to predict drug-resistant pathogens in hemodialysis-associated
pneumonia.
AB - BACKGROUND: After the concept of healthcare associated pneumonia (HCAP) was
introduced in 2005 by the American Thoracic Society/Infectious Disease Society of
America (ATS/IDSA), pneumonia in hemodialysis patients has been classified as
HCAP. Even though there are several risk factors and scoring systems of drug
resistant pathogens (DRPs) in HCAP, the risk factors for DRPs in hemodialysis
associated pneumonia are unclear. METHODS: Patients who were admitted to our
tertiary care hospital from January 2005 to December 2010 were screened by a
discharge diagnosis of pneumonia. Patients were enrolled if they fulfilled the
definition of HCAP according to the 2005 ATS/IDSA guidelines. RESULTS: A total of
530 subjects were diagnosed with HCAP, of whom 48 (9.1 %) received regular
hemodialysis (HD group) and the other 482 did not (non-HD group). The most common
pathogens in HD group were Pseudomonas aeruginosa and methicillin resistant
Staphylococcus aureus (MRSA). There was a similar distribution of Gram-negative
bacilli infections between the two groups except for Haemophilus influenzae and
Citrobacter species. The incidence of DRPs was not significantly different
between the two groups (HD vs. non-HD, 35.4 vs. 39.2 %, p = 0.607). Wound care,
severe pneumonia and an age of more than 70 years were significant risk factors
for DRPs. The area under the operating cure of predicting DRPs was 0.727 (0.575
0.879, p = 0.01). CONCLUSION: P. aeruginosa and MRSA were the most important
pathogens in hemodialysis-associated pneumonia. Wound care, severe pneumonia and
old age were significant risk factors for DRPs.
PMID- 27502600
TI - The clinical utility of serum IL-35 in patients with polymyositis and
dermatomyositis.
AB - The objectives of this study are to assess the levels of serum Interleukin-35 (IL
35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate
the association between IL-35 levels and IIM-related features. Serum IL-35 was
detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis
(PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus
erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)),
and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients. Serum
IL-35 was higher in myositis (PM/DM) patients than in healthy controls (median
76.6 pg/ml [interquartile range (IQR) 57.9-136.2] vs. 29.9 pg/ml (IQR 21.9-65.5),
P < 0.001) and disease controls. Serum IL-35 in IIM patients negatively
correlated with disease duration moderately (r = -0.35, P < 0.01). Patients with
dysphagia had higher IL-35 than those without (median149.35 pg/ml (IQR 87.97
267.32) vs. 70.72 pg/ml (IQR 54.49-123.42), P = 0.001). Cross-sectional
correlation analysis showed a weak positive correlation between serum IL-35 and
CK (r = 0.293, P = 0.003), moderate positive correlation with erythrocyte
sedimentation rate (ESR) (r = 0.304, P = 0.002), serum ferritin (SF) (r = 0.467,
P = 0.001) and LDH levels (r = 0.401, P < 0.001). Additionally, serum IL-35 was
higher in patients who were positive for anti-HMGCR (median 292.04 pg/ml (IQR
67.9-442.86) vs. 74.66 pg/ml (IQR 57.24-131.32), P = 0.038) and anti-SRP antibody
(median 130.33 pg/ml (IQR 88.04-481.28) vs. 73.06 pg/ml (IQR 56.78-134.28), P =
0.009) than in negative patients, respectively. Follow-up study showed that
changes in IL-35 levels after treatment correlated with changes in MYOACT scores
moderately (r = 0.375, P = 0.029). These data indicate that increased serum IL-35
could act as a disease activity marker and as a risk factor for esophageal
involvement in IIM. IL-35 may participate in the pathophysiological processes of
IIM, but it still needs further study to confirm.
PMID- 27502601
TI - DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control.
AB - Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are an emerging class of
antidiabetic drugs that constitutes approximately fifty percent of the market
share of the oral hypoglycemic drugs. Its mechanism of action for lowering blood
glucose is essentially via inhibition of the rapid degradation of incretin
hormones, such as glucagon-like peptide (GLP)-1 and gastric inhibitory
polypeptide (GIP), thus the plasma concentration of GLP-1 increases, which
promotes insulin secretion from the pancreatic beta cells and suppresses glucagon
secretion from the alpha cells. In addition to the direct actions on the
pancreas, GLP-1 exhibits diverse actions on different tissues through its action
on GLP-1 receptor, which is expressed ubiquitously. Moreover, DPP-4 has multiple
substrates besides GLP-1 and GIP, including cytokines, chemokines, neuropeptides,
and growth factors, which are involved in many pathophysiological conditions.
Recently, it was suggested that DPP-4 is a new adipokine secreted from the
adipose tissue, which plays an important role in the regulation of the endocrine
function in obesity-associated type 2 diabetes. Consequently, DPP-4 inhibitors
have been reported to exhibit cytoprotective functions against various diabetic
complications affecting the liver, heart, kidneys, retina, and neurons. This
review outlines the current understanding of the effect of DPP-4 inhibitors on
the complications associated with type 2 diabetes, such as liver steatosis and
inflammation, dysfunction of the adipose tissue and pancreas, cardiovascular
diseases, nephropathy, and neuropathy in preclinical and clinical studies.
PMID- 27502602
TI - Papaya CpERF9 acts as a transcriptional repressor of cell-wall-modifying genes
CpPME1/2 and CpPG5 involved in fruit ripening.
AB - KEY MESSAGE: CpERF9 controls papaya fruit ripening through transcriptional
repression of cell-wall-modifying genes CpPME1/2 and CpPG5 by directly binding to
their promoters. Papaya fruit ripening is an intricate and highly coordinated
developmental process which is controlled by the action of ethylene and
expression of numerous ethylene-responsive genes. Ethylene response factors
(ERFs) representing the last regulators of ethylene-signaling pathway determine
the specificities of ethylene response. However, knowledge concerning the
transcriptional controlling mechanism of ERF-mediated papaya fruit ripening is
limited. In the present work, a gene-encoding AP2/ERF protein with two ERF
associated amphiphilic repression (EAR) motifs, named CpERF9, was characterized
from papaya fruit. CpERF9 was found to localize in nucleus, and possess
transcriptional repression ability. CpERF9 expression steadily decreased during
papaya fruit ripening, while several genes encoding pectin methylesterases (PMEs)
and polygalacturonases (PGs), such as CpPME1/2 and CpPG5, were gradually
increased, paralleling the decline of fruit firmness. Electrophoretic mobility
shift assay (EMSA) demonstrated a specific binding of CpERF9 to promoters of
CpPME1/2 and CpPG5, via the GCC-box motif. Transient expression of CpERF9 in
tobacco repressed CpPME1/2 and CpPG5 promoter activities, which was depended on
two EAR motifs of CpERF9 protein. Taken together, these findings suggest that
papaya CpERF9 may act as a transcriptional repressor of several cell-wall
modifying genes, such as CpPME1/2 and CpPG5, via directly binding to their
promoters.
PMID- 27502603
TI - Do perfusion and diffusion MRI predict glioblastoma relapse sites following
chemoradiation?
AB - To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and
diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after
chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy
(60 Gy) and concomitant temozolomide for glioblastoma, who were included in the
reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed
and their imaging data were analyzed. All patients underwent anatomical MRI, DSC
MRI and DWI before radiotherapy and every 2 months thereafter until relapse.
Voxels within the sites of relapse were correlated with their perfusion and/or
diffusion abnormality (PDA) pretreatment status after rigid co-registration. The
relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC)
were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels
using a 1.75 fixed rCBV threshold (HPt); hypoperfused (hPg) and hyperperfused
(HPg) voxels using a histogram-based Gaussian method; diffusion-restricted voxels
(DRg); and HPg voxels with diffusion restriction (HPg&DRg). Two sets of voxels
(2,459,483 and 2,073,880) were analyzed according to these thresholding methods.
Positive predictive values (PPV) of PDA voxels were low (between 9.5 and 31.9 %).
The best PPV was obtained with HPg&DRg voxels within the FLAIR hyperintensity, as
18.3 % of voxels without initial PDA were within relapse sites, versus 31.9 %
with initial PDA (p < 0.0001). This prospective study suggests that DSC and/or
DWI-MRI do not predict the glioblastoma relapse sites. However, further
investigations with new methodological approaches are needed to better understand
the role of these modalities in the prediction of glioblastoma relapse sites.
PMID- 27502604
TI - Young systemic factors as a medicine for age-related neurodegenerative diseases.
AB - It is widely known that neurogenesis, brain function and cognition decline with
aging. Increasing evidence suggests that cerebrovascular dysfunction is a major
cause of cognitive impairment in the elderly but is also involved in age-related
neurodegenerative diseases. Finding ways and molecules that reverse this process
and ameliorate age- and disease-related cognitive impairment by targeting
vascular and neurogenic deterioration would be of great therapeutic value. In
Katsimpardi et al. we reported that young blood has a dual beneficial effect in
the aged brain by restoring age-related decline in neurogenesis as well as
inducing a striking remodeling of the aged vasculature and restoring blood flow
to youthful levels. Additionally, we identified a youthful systemic factor, GDF11
that recapitulates these beneficial effects of young blood. We believe that the
identification of young systemic factors that can rejuvenate the aged brain opens
new roads to therapeutic intervention for neurodegenerative diseases by targeting
both neural stem cells and neurogenesis as well as at the vasculature.
PMID- 27502605
TI - Accreditation for centers of sarcoma surgery.
AB - Soft-tissue sarcomas (STS) are a heterogeneous group of neoplasms which may be
subclassified into over 70 specific histologies and may be distributed throughout
the body. Approximately one-half arises in the extremities and one-third arises
in the abdomen, pelvis, and retroperitoneum. The diversity and rarity of sarcomas
combined with the quite large number of affected patients are factors which
underline of the importance of networking in diagnosis, therapy, and research
dealing with rare cancers. The expertise of the treating center is one of the
most significant factors affecting survival in STS. The optimal treatment of
locally recurrent disease is to prevent it; aggressive multidisciplinary
treatment of the primary disease is thus required, as adjuvant therapies cannot
compensate for inadequate surgery. Treatment within specialized multidisciplinary
teams (MDTs) is crucial; a body of expertise in all the areas of diagnosis and
treatment is required to manage STS appropriately. Conformity to approved
treatment guidelines is improved when patients are treated by an MDT in a
reference centre. Traditionally, peer-reviewed literature has discussed the
surgical management of STS based on the site of origin. While the site of origin
remains an important consideration, it has become increasingly clear that surgery
must also be tailored to specific sarcoma histology to more accurately reflect
tumor biology and pattern of recurrence. All sarcoma operations, included
retroperitoneal surgery, should be performed in specialized centres to ensure
optimal outcomes.
PMID- 27502606
TI - Treatment of branch-duct intraductal papillary mucinous neoplasms of the
pancreas: state of the art.
AB - The diagnosis of branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs)
has been dramatically increased. BD-IPMNs are frequently discovered as incidental
findings in asymptomatic individuals, mainly in elderly patients. An accurate
evaluation of BD-IPMNs with high-resolution imaging techniques and endoscopic
ultrasound is necessary. Patients with high-risk stigmata (HRS, obstructive
jaundice, enhanced solid component) should undergo resection. Patients with
worrisome features (WF, cyst size >=3 cm, thickened enhanced cyst walls, non
enhanced mural nodules, and clinical acute pancreatitis) may undergo either a
strict surveillance based on patients' characteristics (age, comorbidities) or
surgical resection. Non-operative management is indicated for BD-IPMNs without
HRS and WF. Patients with BD-IPMN who do not undergo resection may develop
malignant change over time as well as IPMN-distinct pancreatic cancer. However,
non-operative management of BD-IPMNs lacking WF and HRS is safe and the risk of
malignant degeneration seems relatively low. The optimal surveillance protocol is
currently unclear.
PMID- 27502607
TI - Echinocandin B biosynthesis: a biosynthetic cluster from Aspergillus nidulans
NRRL 8112 and reassembly of the subclusters Ecd and Hty from Aspergillus
pachycristatus NRRL 11440 reveals a single coherent gene cluster.
AB - BACKGROUND: Echinocandins are nonribosomal lipopeptides produced by ascommycete
fungi. Due to their strong inhibitory effect on fungal cell wall biosynthesis and
lack of human toxicity, they have been developed to an important class of
antifungal drugs. Since 2012, the biosynthetic gene clusters of most of the main
echinocandin variants have been characterized. Especially the comparison of the
clusters allows a deeper insight for the biosynthesis of these complex
structures. RESULTS: In the genome of the echinocandin B producer Aspergillus
nidulans NRRL 8112 we have identified a gene cluster (Ani) that encodes
echinocandin biosynthesis. Sequence analyses showed that Ani is clearly delimited
from the genomic context and forms a monophyletic lineage with the other
echinocandin gene clusters. Importantly, we found that the disjunct genomic
location of the echinocandin B gene cluster in A. pachycristatus NRRL 11440 on
two separate subclusters, Ecd and Hty, at two loci was likely an artifact of
genome misassembly in the absence of a reference sequence. We show that both
sequences can be aligned resulting a single cluster with a gene arrangement
collinear compared to other clusters of Aspergillus section Nidulantes. The
reassembled gene cluster (Ecd/Hty) is identical to a putative gene cluster (AE)
that was previously deposited at the NCBI as a sequence from A. delacroxii NRRL
3860. PCR amplification of a part of the gene cluster resulted a sequence that
was very similar (97 % identity), but not identical to that of AE. CONCLUSIONS:
The Echinocandin B biosynthetic cluster from A. nidulans NRRL 8112 (Ani) is
particularly similar to that of A. pachycristatus NRRL 11440 (Ecd/Hty). Ecd/Hty
was originally reported as two disjunct sub-clusters Ecd and Hty, but is in fact
a continuous sequence with the same gene order as in Ani. According to sequences
of PCR products amplified from genomic DNA, the echinocandin B producer A.
delacroxii NRRL 3860 is closely related to A. pachycristatus NRRL 11440. A PCR
product from the gene cluster was very similar, but clearly distinct from the
sequence published for A. delacroxii NRRL 3860 at the NCBI (No. AB720074). As the
NCBI entry is virtually identical with the re-assembled Ecd/Hty cluster, it is
likely that it originates from A. pachycristatus NRRL 11440 rather than A.
delacroxii NRRL 3860.
PMID- 27502609
TI - Extracorporeal membrane oxygenation in burn patients with refractory acute
respiratory distress syndrome leads to 28 % 90-day survival.
PMID- 27502610
TI - Editor's Note.
PMID- 27502608
TI - GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion
Formation in Apolipoprotein E-Null Mice.
AB - Growth differentiation factor 11 (GDF11) reduces cardiac hypertrophy, improves
cerebral vasculature and enhances neurogenesis in ageing mice. Higher growth
differentiation factor 11/8 (GDF11/8) is associated with lower risk of
cardiovascular events in humans. Here, we showed that adeno-associated viruses
GDF11 and recombinant GDF11 protein improve endothelial dysfunction, decrease
endothelial apoptosis, and reduce inflammation, consequently decrease
atherosclerotic plaques area in apolipoprotein E-/- mice. Moreover, adeno
associated viruses-GDF11 and recombinant GDF11 stabilize atherosclerotic plaques
by selectively decreasing in macrophages and T lymphocytes, while increasing in
collagen and vascular smooth muscle cells within plaques. In addition, GDF11
inhibit palmitic acid-induced endothelial apoptosis and ameliorate palmitic acid
induced inflammatory response in RAW264.7 macrophages in vitro. Mechanistically,
GDF11 activates the TGF-beta/Smad2/3, AMPK/endothelial nitricoxide synthase
(eNOS) while suppresses JNK and NF-kappaB pathways. In humans, circulating
GDF11/8 is positively associated with flow-mediated endothelium-dependent
dilation in overweight subjects. We concluded that adeno-associated viruses-GDF11
and recombinant GDF11 protect against endothelial injury and reduce
atherosclerosis in apolipoprotein E-/- mice, thus may be providing a novel
approach to the treatment of atherosclerosis.
PMID- 27502611
TI - Compassionate Care Through the Centuries: Highlights in Nursing History.
PMID- 27502612
TI - "Endeavoring to Carry On Their Work": The National Debate Over Midwives and Its
Impact in Rhode Island, 1890-1940.
AB - This article analyzes the national discourse over "the problem" of midwifery in
medical literature and examines the impact of this dialogue on Rhode Island from
1890 to 1940. Doctors did not speak as a monolithic bloc on this "problem": some
blamed midwives while others impugned poorly trained physicians. This debate led
to curricula reform and to state laws to regulate midwifery. The attempt to
eliminate midwives in the 1910s failed because of a shortage of trained
obstetricians, and because of cultural barriers between immigrant and mainstream
communities. A decrease in immigration, an increase in trained obstetricians, the
growing notion of midwives as relics of an outdated past, and the emergence of
insurance plans to cover "modern" hospital births led to a decline in midwifery.
PMID- 27502613
TI - "A Powerful Protector of the Japanese People": The History of the Japanese
Hospital in Steveston, British Columbia, Canada,1896-1942.
AB - From 1896 to 1942, a Japanese hospital operated in the village of Steveston,
British Columbia, Canada. For the first 4 years, Japanese Methodist missionaries
utilized a small mission building as a makeshift hospital, until a larger
institution was constructed by the local Japanese Fishermen's Association in
1900. The hospital operated until the Japanese internment, after the attack on
Pearl Harbor during World War II. This study offers important commentary about
the relationships between health, hospitals, and race in British Columbia during
a period of increased immigration and economic upheaval. From the unique
perspective of Japanese leaders, this study provides new insight about how
Japanese populations negotiated hospital care, despite a context of severe racial
discrimination. Japanese populations utilized Christianization, fishing
expertise, and hospital work to garner more equitable access to opportunities and
resources. This study demonstrates that in addition to providing medical
treatment, training grounds for health-care workers, and safe refuge for the
sick, hospitals played a significant role in confronting broader racialized
inequities in Canada's past.
PMID- 27502614
TI - Confectionery Care: The Child as a Category of Historical Analysis.
PMID- 27502616
TI - "Mother: Here's the Aspirin Tablet That 'Fits' Your Child's Needs"-"Candy"
Aspirin and Children, 1947-1960.
PMID- 27502618
TI - Media Reviews.
PMID- 27502617
TI - Playing Doctor, Playing Nurse: Perspectives on the Origins of the Toy Doctor and
Nurse Kits.
PMID- 27502619
TI - Use of customised pressure-guided elastic bandages to improve efficacy of
compression bandaging for venous ulcers.
AB - Compression bandaging is a major treatment of chronic venous ulcers. Its efficacy
depends on the applied pressure, which is dependent on the skill of the
individual applying the bandage. To improve the quality of bandaging by reducing
the variability in compression bandage interface pressures, we changed elastic
bandages into a customised version by marking them with circular ink stamps,
applied when the stretch achieves an interface pressure between 35 and 45 mmHg.
Repeated applications by 20 residents of the customised bandage and non-marked
bandage to one smaller and one larger leg were evaluated by measuring the sub
bandage pressure. The results demonstrated that the target pressure range is more
often attained with the customised bandage compared with the non-marked bandage.
The customised bandage improved the efficacy of compression bandaging for venous
ulcers, with optimal sub-bandage pressure.
PMID- 27502620
TI - Mathematical analysis of the sodium sensitivity of the human histamine H3
receptor.
AB - PURPOSE: It was shown by several experimental studies that some G protein coupled
receptors (GPCR) are sensitive to sodium ions. Furthermore, mutagenesis studies
or the determination of crystal structures of the adenosine A2A or delta-opioid
receptor revealed an allosteric Na(+) binding pocket near to the highly conserved
Asp(2.50). Within a previous study, the influence of NaCl concentration onto the
steady-state GTPase activity at the human histamine H3 receptor (hH3R) in
presence of the endogenous histamine or the inverse agonist thioperamide was
analyzed. The purpose of the present study was to examine and quantify the Na(+)
sensitivity of hH3R on a molecular level. METHODS: To achieve this, we developed
a set of equations, describing constitutive activity and the different ligand
receptor equilibria in absence or presence of sodium ions. Furthermore, in order
to gain a better understanding of the ligand- and Na(+)-binding to hH3R on
molecular level, we performed molecular dynamic (MD) simulations. RESULTS: The
analysis of the previously determined experimental steady-state GTPase data with
the set of equations presented within this study, reveals that thioperamide binds
into the orthosteric binding pocket of the hH3R in absence or presence of a Na(+)
in its allosteric binding site. However, the data suggest that thioperamide binds
preferentially into the hH3R in absence of a sodium ion in its allosteric site.
These experimental results were supported by MD simulations of thioperamide in
the binding pocket of the inactive hH3R. Furthermore, the MD simulations revealed
two different binding modes for thioperamide in presence or absence of a Na(+) in
its allosteric site. CONCLUSION: The mathematical model presented within this
study describes the experimental data regarding the Na(+)-sensitivity of hH3R in
an excellent manner. Although the present study is focused onto the Na(+)
sensitivity of the hH3R, the resulting equations, describing Na(+)- and ligand
binding to a GPCR, can be used for all other ion-sensitive GPCRs.
PMID- 27502622
TI - Arab Journal of Gastroenterology: A rising star.
PMID- 27502621
TI - In silico evaluation of gadofosveset pharmacokinetics in different population
groups using the Simcyp(r) simulator platform.
AB - PURPOSE: Gadofosveset is a Gd-based contrast agent used for magnetic resonance
imaging (MRI). Gadolinium kinetic distribution models are implemented in T1
weighted dynamic contrast-enhanced perfusion MRI for characterization of lesion
sites in the body. Physiology changes in a disease state potentially can
influence the pharmacokinetics of drugs and to this respect modify the
distribution properties of contrast agents. This work focuses on the in silico
modelling of pharmacokinetic properties of gadofosveset in different population
groups through the application of physiologically-based pharmacokinetic models
(PBPK) embedded in Simcyp(r) population pharmacokinetics platform. METHODS:
Physicochemical and pharmacokinetic properties of gadofosveset were introduced
into Simcyp(r) simulator platform and a min-PBPK model was applied. In silico
clinical trials were generated simulating the administration of the recommended
dose for the contrast agent (i.v., 30 mg/kg) in population cohorts of healthy
volunteers, obese, renal and liver impairment, and in a generated virtual
oncology population. Results were evaluated regarding basic pharmacokinetic
parameters of Cmax, AUC and systemic CL and differences were assessed through
ANOVA and estimation of ratio of geometric mean between healthy volunteers and
the other population groups. RESULTS: Simcyp(r) predicted a mean Cmax = 551.60
mg/l, a mean AUC = 4079.12 mg/L*h and a mean systemic CL = 0.56 L/h for the
virtual population of healthy volunteers. Obese population showed a modulation in
Cmax and CL, attributed to increased administered dose. In renal and liver
impairment cohorts a significant modulation in Cmax, AUC and CL of gadofosveset
is predicted. Oncology population exhibited statistical significant differences
regarding AUC when compared with healthy volunteers. CONCLUSIONS: This work
employed Simcyp(r) population pharmacokinetics platform in order to compute
gadofosveset's pharmacokinetic profiles through PBPK models and in silico
clinical trials and evaluate possible differences between population groups. The
approach showed promising results that could provide new insights regarding
administration of contrast agents in special population cohorts. In silico
pharmacokinetics could further be used for evaluating of possible toxicity,
interpretation of MRI PK image maps and development of novel contrast agents.
PMID- 27502623
TI - Radial head button holing: a cause of irreducible anterior radial head
dislocation.
AB - "Buttonholing" of the radial head through the anterior joint capsule is a known
cause of irreducible anterior radial head dislocation associated with Monteggia
injuries in pediatric patients. To the best of our knowledge, no report has
described an injury consisting of buttonholing of the radial head through the
annular ligament and a simultaneous radial head fracture in an adolescent. In the
present case, the radiographic findings were a radial head fracture with anterior
dislocation and lack of the anterior fat pad sign. Magnetic resonance imaging
(MRI) clearly demonstrated anterior dislocation of the fractured radial head
through the torn annular ligament. The anterior joint capsule and proximal
portion of the annular ligament were interposed between the radial head and
capitellum, preventing closed reduction of the radial head. Familiarity with this
condition and imaging findings will aid clinicians to make a proper diagnosis and
fast decision to perform an open reduction.
PMID- 27502624
TI - Glenoid avulsion of the glenohumeral ligament (GAGL): a case report and review of
the anatomy.
AB - Shoulder dislocations are frequently seen in the general population and can be a
cause of instability. Instability can lead to debilitating symptoms and morbidity
as a result of progressive damage to the shoulder. Anterior shoulder dislocations
are the most frequent type of dislocations and have been studied extensively with
MRI. The soft tissue Bankart lesion is the most well-known entity associated with
anterior instability; however, additional structural lesions arising from
traumatic events have been described in recent literature which also predispose
to anterior shoulder instability. One of these lesions, the glenoid avulsion of
the glenohumeral ligament (GAGL), involves avulsion of the inferior glenohumeral
ligament from the glenoid and involves separation from an intact labrum. In
contrast to the Bankart lesion, there has been limited discussion of the GAGL
lesion in the literature and very few imaging examples. We report a case of a
GAGL diagnosed on MRI and confirmed with arthroscopy. It is discussed in the
context of the anatomy of the inferior glenohumeral ligament and the imaging
findings.
PMID- 27502626
TI - Real-life experience with intravitreal ocriplasmin on vitreomacular traction and
full-thickness macular holes.
PMID- 27502625
TI - Short- and midterm reproducibility of marrow fat measurements using mDixon
imaging in healthy postmenopausal women.
AB - OBJECTIVE: We tested the short- and midterm reproducibility of vertebral marrow
fat fraction (FF) measurements using mDixon imaging. MATERIALS AND METHODS:
Thirty postmenopausal women underwent mDixon scans to obtain L1-4 FF from three
slices per vertebra by two independent observers (session 1). Measurements were
repeated after 6 weeks (session 2) and 6 months (session 3). The mean FF for
three regions of interest per vertebra was calculated. The coefficients of
variation (CVs) were calculated for each participant and imaging session, and the
intraclass correlation coefficients (ICCs) were calculated to assess
interobserver and intersession agreements. RESULTS: There were no significant
differences in FF measurements among the three slices, imaging sessions or
observers. The mean intrasubject CV for FF measurement reproducibility was 1.94
%. The interobserver agreement for the average FF value was excellent (ICC
>=0.945 for each session). The ICC for intersession agreement was excellent (ICC
>=0.955 between sessions). The mean intersession CV was lower within a short-term
interval (2.97 %) than within sessions 1 and 3 (4.80 %) or sessions 3 and 2 (4.44
%). The overall mean CV for the reproducibility of FF measured with mDixon
imaging over the short- and midterm was 4.09 % (95 % CI, 3.79-4.40 %).
CONCLUSION: mDixon is a reproducible method for FF quantification over short- and
midterm intervals up to 6 months in healthy postmenopausal women. Our results
also provide data by which a power analysis can be optimized when designing
studies involving the use of FF derived from similar mDixon sequences.
PMID- 27502627
TI - Cancer burden in four countries of the Middle East Cancer Consortium (Cyprus;
Jordan; Israel; Izmir (Turkey)) with comparison to the United States
surveillance; epidemiology and end results program.
AB - It is important that population-based cancer registries provide accurate and
reliable data for public health purposes. These data are essential data for
planning of cancer control and prevention. In this study, we examined cancer
incidence rates (year 2005-2010) in four MECC registries (Cyprus, Jordan, Israel,
Izmir (Turkey)) and compared with the rates in the US. The overall age
standardized incidence rates for males were highest in the US followed by Israeli
Jews, Izmir (Turkey), Cyprus, Israeli Arabs, and lowest in Jordan. In women the
rates of cancer of all sites were also highest in US women followed by Israeli
Jews, Cyprus, Israeli Arabs, Izmir (Turkey), and lowest in Jordan. It is of
interest that although site-specific cancer rates differ between the countries
studied, prostate, lung and colorectal cancers are within the five most common
cancers males in all countries studied. In females, breast colorectal and
endometrium cancers are three of the five most common cancers in females in all
countries studied. The results presented in this paper can have implications for
opportunities in cancer control and prevention in these countries. Future studies
on individual cancer sites with highest rates in these Countries are currently
underway.
PMID- 27502628
TI - Investigation of Nucleation Mechanism and Tapering Observed in ZnO Nanowire
Growth by Carbothermal Reduction Technique.
AB - ZnO nanowire nucleation mechanism and initial stages of nanowire growth using the
carbothermal reduction technique are studied confirming the involvement of the
catalyst at the tip in the growth process. Role of the Au catalyst is further
confirmed when the tapering observed in the nanowires can be explained by the
change in the shape of the catalyst causing a variation of the contact area at
the liquid-solid interface of the nanowires. The rate of decrease in nanowire
diameter with length on the average is found to be 0.36 nm/s and this rate is
larger near the base. Variation in the ZnO nanowire diameter with length is
further explained on the basis of the rate at which Zn atoms are supplied as well
as the droplet stability at the high flow rates and temperature. Further, saw
tooth faceting is noticed in tapered nanowires, and the formation is analyzed
crystallographically.
PMID- 27502629
TI - Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for
Cancer Chemotherapy.
AB - Three types of nanoparticle formulation from biodegradable PLGA-TPGS random
copolymer were developed in this research for oral administration of anticancer
drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS
nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS
random copolymer was synthesized and characterized. DMAB was used to increase
retention time at the cell surface, thus increasing the chances of particle
uptake and improving oral drug bioavailability. Nanoparticles were found to be of
spherical shape with an average particle diameter of around 250 nm. The surface
charge of PLGA-TPGS nanoparticles was changed to positive after DMAB
modification. The results also showed that the DMAB-modified PLGA-TPGS
nanoparticles have significantly higher level of the cellular uptake than that of
DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In
vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS
nanoparticle formulation over commercial Taxotere((r)) in terms of cytotoxicity
against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS
nanoparticle formulation is an attractive and promising treatment option for
patients.
PMID- 27502630
TI - Optical Properties of GaSb Nanofibers.
AB - Amorphous GaSb nanofibers were obtained by ion beam irradiation of bulk GaSb
single-crystal wafers, resulting in fibers with diameters of ~20 nm. The Raman
spectra and photoluminescence (PL) of the ion irradiation-induced nanofibers
before and after annealing were studied. Results show that the Raman intensity of
the GaSb LO phonon mode decreased after ion beam irradiation as a result of the
formation of the amorphous nanofibers. A new mode is observed at ~155 cm(-1) both
from the unannealed and annealed GaSb nanofiber samples related to the A1g mode
of Sb-Sb bond vibration. Room temperature PL measurements of the annealed
nanofibers present a wide feature band at ~1.4-1.6 eV. The room temperature PL
properties of the irradiated samples presents a large blue shift compared to bulk
GaSb. Annealed nanofibers and annealed nanofibers with Au nanodots present two
different PL peaks (400 and 540 nm), both of which may originate from Ga or O
vacancies in GaO. The enhanced PL and new band characteristics in nanostructured
GaSb suggest that the nanostructured fibers may have unique applications in
optoelectronic devices.
PMID- 27502631
TI - Sensitivity of Dielectric Properties to Wear Process on Carbon Nanofiber/High
Density Polyethylene Composites.
AB - We examined the correlation of wear effects with dielectric properties of carbon
nanofibers (CNFs; untreated and organosilane-treated)-reinforced high-density
polyethylene (HDPE) composites. Wear testing for the nanocomposites over up to
120 h was carried out, and then, dielectric permittivity and dielectric loss
factor of the polymer composites with the increased wear time were studied.
Scanning electron microscope and optical microscope observations were made to
analyze the microstructure features of the nanocomposites. The results reveal
that there exist approximate linear relationships of permittivity with wear
coefficient for the nanocomposites. Composites containing silanized CNFs with the
sufficiently thick coating exhibited high wear resistance. The change in
permittivity was more sensitive to the increased wear coefficient for the
nanocomposites with lower wear resistance. This work provides potential for
further research on the application of dielectric signals to detect the effects
of wear process on lifetime of polymeric materials.
PMID- 27502632
TI - Biocompatibility of Graphene Oxide.
AB - Herein, we report the effects of graphene oxides on human fibroblast cells and
mice with the aim of investigating graphene oxides' biocompatibility. The
graphene oxides were prepared by the modified Hummers method and characterized by
high-resolution transmission electron microscope and atomic force microscopy. The
human fibroblast cells were cultured with different doses of graphene oxides for
day 1 to day 5. Thirty mice divided into three test groups (low, middle, high
dose) and one control group were injected with 0.1, 0.25, and 0.4 mg graphene
oxides, respectively, and were raised for 1 day, 7 days, and 30 days,
respectively. Results showed that the water-soluble graphene oxides were
successfully prepared; graphene oxides with dose less than 20 MUg/mL did not
exhibit toxicity to human fibroblast cells, and the dose of more than 50 MUg/mL
exhibits obvious cytotoxicity such as decreasing cell adhesion, inducing cell
apoptosis, entering into lysosomes, mitochondrion, endoplasm, and cell nucleus.
Graphene oxides under low dose (0.1 mg) and middle dose (0.25 mg) did not exhibit
obvious toxicity to mice and under high dose (0.4 mg) exhibited chronic toxicity,
such as 4/9 mice death and lung granuloma formation, mainly located in lung,
liver, spleen, and kidney, almost could not be cleaned by kidney. In conclusion,
graphene oxides exhibit dose-dependent toxicity to cells and animals, such as
inducing cell apoptosis and lung granuloma formation, and cannot be cleaned by
kidney. When graphene oxides are explored for in vivo applications in animal or
human body, its biocompatibility must be considered.
PMID- 27502633
TI - Interaction of Water-Soluble CdTe Quantum Dots with Bovine Serum Albumin.
AB - Semiconductor nanoparticles (quantum dots) are promising fluorescent markers, but
it is very little known about interaction of quantum dots with biological
molecules. In this study, interaction of CdTe quantum dots coated with
thioglycolic acid (TGA) with bovine serum albumin was investigated. Steady state
spectroscopy, atomic force microscopy, electron microscopy and dynamic light
scattering methods were used. It was explored how bovine serum albumin affects
stability and spectral properties of quantum dots in aqueous media. CdTe-TGA
quantum dots in aqueous solution appeared to be not stable and precipitated.
Interaction with bovine serum albumin significantly enhanced stability and
photoluminescence quantum yield of quantum dots and prevented quantum dots from
aggregating.
PMID- 27502634
TI - Assessment of Influence of Magnetic Forces on Aggregation of Zero-valent Iron
Nanoparticles.
AB - Aggregation of zero-valent nanoparticles in groundwater is influenced by several
physical phenomena. The article shortly introduces preceding works in modeling of
aggregation of small particles including influence of sedimentation, velocity
profile of water, heat fluctuations, and surface electric charge. A brief
description of inclusion of magnetic forces into the model of aggregation
follows. Rate of influence of the magnetic forces on the aggregation depends on
the magnitude of magnetization of the particles, radius of nanoparticles, size of
the aggregates, and their concentration in the solution. Presented results show
that the magnetic forces have significant influence on aggregation especially of
the smallest iron particles.
PMID- 27502635
TI - In situ-Directed Growth of Organic Nanofibers and Nanoflakes: Electrical and
Morphological Properties.
AB - Organic nanostructures made from organic molecules such as para-hexaphenylene (p
6P) could form nanoscale components in future electronic and optoelectronic
devices. However, the integration of such fragile nanostructures with the
necessary interface circuitry such as metal electrodes for electrical connection
continues to be a significant hindrance toward their large-scale implementation.
Here, we demonstrate in situ-directed growth of such organic nanostructures
between pre-fabricated contacts, which are source-drain gold electrodes on a
transistor platform (bottom-gate) on silicon dioxide patterned by a combination
of optical lithography and electron beam lithography. The dimensions of the gold
electrodes strongly influence the morphology of the resulting structures leading
to notably different electrical properties. The ability to control such nanofiber
or nanoflake growth opens the possibility for large-scale optoelectronic device
fabrication.
PMID- 27502636
TI - Arc Discharge Synthesis and Photoluminescence of 3D Feather-like AlN
Nanostructures.
AB - A complex three-dimensional (3D) feather-like AlN nanostructure was synthesized
by a direct reaction of high-purity Al granules with nitrogen using an arc
discharge method. By adjusting the discharge time, a coral-like nanostructure,
which evolved from the feather-like nanostructure, has also been observed. The
novel 3D feather-like AlN nanostructure has a hierarchical dendritic structure,
which means that the angle between the trunk stem and its branch is always about
30 degrees in any part of the structure. The fine branches on the surface of the
feather-like nanostructure have shown a uniform fish scale shape, which are about
100 nm long, 10 nm thick and several tens of nanometers in width. An alternate
growth model has been proposed to explain the novel nanostructure. The spectrum
of the feather-like products shows a strong blue emission band centered at 438 nm
(2.84 eV), which indicates their potential application as blue light-emitting
diodes.
PMID- 27502637
TI - Perpendicular Magnetic Anisotropy in FePt Patterned Media Employing a CrV Seed
Layer.
AB - A thin FePt film was deposited onto a CrV seed layer at 400 degrees C and showed
a high coercivity (~3,400 Oe) and high magnetization (900-1,000 emu/cm(3))
characteristic of L 10 phase. However, the magnetic properties of patterned media
fabricated from the film stack were degraded due to the Ar-ion bombardment. We
employed a deposition-last process, in which FePt film deposited at room
temperature underwent lift-off and post-annealing processes, to avoid the
exposure of FePt to Ar plasma. A patterned medium with 100-nm nano-columns showed
an out-of-plane coercivity fivefold larger than its in-plane counterpart and a
remanent magnetization comparable to saturation magnetization in the out-of-plane
direction, indicating a high perpendicular anisotropy. These results demonstrate
the high perpendicular anisotropy in FePt patterned media using a Cr-based
compound seed layer for the first time and suggest that ultra-high-density
magnetic recording media can be achieved using this optimized top-down approach.
PMID- 27502638
TI - In situ Precursor-Template Route to Semi-Ordered NaNbO3 Nanobelt Arrays.
AB - We exploited a precursor-template route to chemically synthesize NaNbO3 nanobelt
arrays. Na7(H3O)Nb6O19.14H2O nanobelt precursor was firstly prepared via a
hydrothermal synthetic route using Nb foil. The aspect ratio of the precursor is
controllable facilely depending on the concentration of NaOH aqueous solution.
The precursor was calcined in air to yield single-crystalline monoclinic NaNbO3
nanobelt arrays. The proposed scheme for NaNbO3 nanobelt formation starting from
Nb metal may be extended to the chemical fabrication of more niobate arrays.
PMID- 27502639
TI - Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and
Release Kinetics.
AB - The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT)
affords an intestine-selective drug delivery system that has a captopril-loading
capacity of up to ca. 14 %w/w and which exhibits near-zero-order release
kinetics.
PMID- 27502640
TI - Biofabrication of Anisotropic Gold Nanotriangles Using Extract of Endophytic
Aspergillus clavatus as a Dual Functional Reductant and Stabilizer.
AB - Biosynthesis of metal and semiconductor nanoparticles using microorganisms has
emerged as a more eco-friendly, simpler and reproducible alternative to the
chemical synthesis, allowing the generation of rare forms such as nanotriangles
and prisms. Here, we report the endophytic fungus Aspergillus clavatus, isolated
from surface sterilized stem tissues of Azadirachta indica A. Juss., when
incubated with an aqueous solution of chloroaurate ions produces a diverse
mixture of intracellular gold nanoparticles (AuNPs), especially nanotriangles
(GNT) in the size range from 20 to 35 nm. These structures (GNT) are of special
interest since they possess distinct plasmonic features in the visible and IR
regions, which equipped them with unique physical and optical properties
exploitable in vital applications such as optics, electronics, catalysis and
biomedicine. The reaction process was simple and convenient to handle and was
monitored using ultraviolet-visible spectroscopy (UV-vis). The morphology and
crystalline nature of the GNTs were determined from transmission electron
microscopy (TEM), atomic force spectroscopy (AFM) and X-ray diffraction (XRD)
spectroscopy. This proposed mechanistic principal might serve as a set of design
rule for the synthesis of anisotropic nanostructures with desired architecture
and can be amenable for the large scale commercial production and technical
applications.
PMID- 27502642
TI - Design and Fabrication of Fiber-Optic Nanoprobes for Optical Sensing.
AB - This paper describes the design and fabrication of fiber-optic nanoprobes
developed for optical detection in single living cells. It is critical to
fabricate probes with well-controlled nanoapertures for optimized spatial
resolution and optical transmission. The detection sensitivity of fiber-optic
nanoprobe depends mainly on the extremely small excitation volume that is
determined by the aperture sizes and penetration depths. We investigate the angle
dependence of the aperture in shadow evaporation of the metal coating onto the
tip wall. It was found that nanoaperture diameters of approximately 50 nm can be
achieved using a 25 degrees tilt angle. On the other hand, the aperture size is
sensitive to the subtle change of the metal evaporation angle and could be
blocked by irregular metal grains. Through focused ion beam (FIB) milling,
optical nanoprobes with well-defined aperture size as small as 200 nm can be
obtained. Finally, we illustrate the use of the nanoprobes by detecting a
fluorescent species, benzo[a]pyrene tetrol (BPT), in single living cells. A
quantitative estimation of the numbers of BPT molecules detected using fiber
optic nanoprobes for BPT solutions shows that the limit of detection was
approximately 100 molecules.
PMID- 27502641
TI - Silver and Gold Nanoparticles Alter Cathepsin Activity In vitro.
AB - Nanomaterials are being incorporated into many biological applications for use as
therapeutics, sensors, or labels. Silver nanomaterials are being utilized for
biological implants and wound dressings as an antiviral material, whereas gold
nanomaterials are being used as biological labels or sensors due to their surface
properties and biocompatibility. Cytotoxicity data of these materials are
becoming more prevalent; however, little research has been performed to
understand how the introduction of these materials into cells affects cellular
processes. Here, we demonstrate the impact that silver and gold nanoparticles
have on cathepsin activity in vitro. Cathepsins are important cellular proteases
that are imperative for proper immune system function. We have selected to
examine gold and silver nanoparticles due to the increased use of these materials
in biological applications. This manuscript depicts how both of these types of
nanomaterials affect cathepsin activity, which could impact the host's immune
system and its ability to respond to pathogens. Cathepsin B activity decreases in
a dose-dependent manner with all nanoparticles tested. Alternatively, the impact
of nanoparticles on cathepsin L activity depends greatly on the type and size of
the material.
PMID- 27502643
TI - Biomagnetic of Apatite-Coated Cobalt Ferrite: A Core-Shell Particle for Protein
Adsorption and pH-Controlled Release.
AB - Magnetic nanoparticle composite with a cobalt ferrite (CoFe2O4, (CF)) core and an
apatite (Ap) coating was synthesized using a biomineralization process in which a
modified simulated body fluid (1.5SBF) solution is the source of the calcium
phosphate for the apatite formation. The core-shell structure formed after the
citric acid-stabilized cobalt ferrite (CFCA) particles were incubated in the 1.5
SBF solution for 1 week. The mean particle size of CFCA-Ap is about 750 nm. A
saturation magnetization of 15.56 emug(-1) and a coercivity of 1808.5 Oe were
observed for the CFCA-Ap obtained. Bovine serum albumin (BSA) was used as the
model protein to study the adsorption and release of the proteins by the CFCA-Ap
particles. The protein adsorption by the CFCA-Ap particles followed a more
typical Freundlich than Langmuir adsorption isotherm. The BSA release as a
function of time became less rapid as the CFCA-Ap particles were immersed in
higher pH solution, thus indicating that the BSA release is dependent on the
local pH.
PMID- 27502644
TI - Quantum Dot Infrared Photodetectors: Photoresponse Enhancement Due to Potential
Barriers.
AB - Potential barriers around quantum dots (QDs) play a key role in kinetics of
photoelectrons. These barriers are always created, when electrons from dopants
outside QDs fill the dots. Potential barriers suppress the capture processes of
photoelectrons and increase the photoresponse. To directly investigate the effect
of potential barriers on photoelectron kinetics, we fabricated several QD
structures with different positions of dopants and various levels of doping. The
potential barriers as a function of doping and dopant positions have been
determined using nextnano(3) software. We experimentally investigated the
photoresponse to IR radiation as a function of the radiation frequency and
voltage bias. We also measured the dark current in these QD structures. Our
investigations show that the photoresponse increases ~30 times as the height of
potential barriers changes from 30 to 130 meV.
PMID- 27502646
TI - Organic-Inorganic Nanostructure Architecture via Directly Capping Fullerenes onto
Quantum Dots.
AB - A new form of fullerene-capped CdSe nanoparticles (PCBA-capped CdSe NPs), using
carboxylate ligands with [60]fullerene capping groups that provides an effective
synthetic methodology to attach fullerenes noncovalently to CdSe, is presented
for usage in nanotechnology and photoelectric fields. Interestingly, either the
internal charge transfer or the energy transfer in the hybrid material
contributes to photoluminescence (PL) quenching of the CdSe moieties.
PMID- 27502645
TI - Biomimetic Synthesis of Gelatin Polypeptide-Assisted Noble-Metal Nanoparticles
and Their Interaction Study.
AB - Herein, the generation of gold, silver, and silver-gold (Ag-Au) bimetallic
nanoparticles was carried out in collagen (gelatin) solution. It first showed
that the major ingredient in gelatin polypeptide, glutamic acid, acted as
reducing agent to biomimetically synthesize noble metal nanoparticles at 80
degrees C. The size of nanoparticles can be controlled not only by the mass ratio
of gelatin to gold ion but also by pH of gelatin solution. Interaction between
noble-metal nanoparticles and polypeptide has been investigated by TEM, UV
visible, fluorescence spectroscopy, and HNMR. This study testified that the
degradation of gelatin protein could not alter the morphology of nanoparticles,
but it made nanoparticles aggregated clusters array (opposing three-dimensional
alpha-helix folding structure) into isolated nanoparticles stabilized by gelatin
residues. This is a promising merit of gelatin to apply in the synthesis of
nanoparticles. Therefore, gelatin protein is an excellent template for biomimetic
synthesis of noble metal/bimetallic nanoparticle growth to form nanometer-sized
device.
PMID- 27502647
TI - Facile Synthesis of Amine-Functionalized Eu(3+)-Doped La(OH)3 Nanophosphors for
Bioimaging.
AB - Here, we report a straightforward synthesis process to produce colloidal Eu(3+)
activated nanophosphors (NPs) for use as bioimaging probes. In this procedure,
poly(ethylene glycol) serves as a high-boiling point solvent allowing for
nanoscale particle formation as well as a convenient medium for solvent exchange
and subsequent surface modification. The La(OH)3:Eu(3+) NPs produced by this
process were ~3.5 nm in diameter as determined by transmission electron
microscopy. The NP surface was coated with aminopropyltriethoxysilane to provide
chemical functionality for attachment of biological ligands, improve chemical
stability and prevent surface quenching of luminescent centers. Photoluminescence
spectroscopy of the NPs displayed emission peaks at 597 and 615 nm (lambdaex =
280 nm). The red emission, due to (5)D0 -> (7)F1 and (5)D0 -> (7)F2 transitions,
was linear with concentration as observed by imaging with a conventional
bioimaging system. To demonstrate the feasibility of these NPs to serve as
optical probes in biological applications, an in vitro experiment was performed
with HeLa cells. NP emission was observed in the cells by fluorescence
microscopy. In addition, the NPs displayed no cytotoxicity over the course of a
48-h MTT cell viability assay. These results suggest that La(OH)3:Eu(3+) NPs
possess the potential to serve as a luminescent bioimaging probe.
PMID- 27502648
TI - Fabrication of Nickel Nanostructure Arrays Via a Modified Nanosphere Lithography.
AB - In this paper, we present a modified nanosphere lithographic scheme that is based
on the self-assembly and electroforming techniques. The scheme was demonstrated
to fabricate a nickel template of ordered nanobowl arrays together with a nickel
nanostructure array-patterned glass substrate. The hemispherical nanobowls
exhibit uniform sizes and smooth interior surfaces, and the shallow nanobowls
with a flat bottom on the glass substrate are interconnected as a net structure
with uniform thickness. A multiphysics model based on the level set method (LSM)
was built up to understand this fabricating process by tracking the interface
between the growing nickel and the electrolyte. The fabricated nickel nanobowl
template can be used as a mold of long lifetime in soft lithography due to the
high strength of nickel. The nanostructure-patterned glass substrate can be used
in optical and magnetic devices due to their shape effects. This fabrication
scheme can also be extended to a wide range of metals and alloys.
PMID- 27502649
TI - The MoS2 Nanotubes with Defect-Controlled Electric Properties.
AB - We describe a two-step synthesis of pure multiwall MoS2 nanotubes with a high
degree of homogeneity in size. The Mo6S4I6 nanowires grown directly from elements
under temperature gradient conditions in hedgehog-like assemblies were used as
precursor material. Transformation in argon-H2S/H2 mixture leads to the MoS2
nanotubes still grouped in hedgehog-like morphology. The described method enables
a large-scale production of MoS2 nanotubes and their size control. X-ray
diffraction, optical absorption and Raman spectroscopy, scanning electron
microscopy with wave dispersive analysis, and transmission electron microscopy
were used to characterize the starting Mo6S4I6 nanowires and the MoS2 nanotubes.
The unit cell parameters of the Mo6S4I6 phase are proposed. Blue shift in optical
absorbance and metallic behavior of MoS2 nanotubes in two-probe measurement are
explained by a high defect concentration.
PMID- 27502650
TI - Role of Surface Area, Primary Particle Size, and Crystal Phase on Titanium
Dioxide Nanoparticle Dispersion Properties.
AB - Characterizing nanoparticle dispersions and understanding the effect of
parameters that alter dispersion properties are important for both environmental
applications and toxicity investigations. The role of particle surface area,
primary particle size, and crystal phase on TiO2 nanoparticle dispersion
properties is reported. Hydrodynamic size, zeta potential, and isoelectric point
(IEP) of ten laboratory synthesized TiO2 samples, and one commercial Degussa TiO2
sample (P25) dispersed in different solutions were characterized. Solution ionic
strength and pH affect titania dispersion properties. The effect of monovalent
(NaCl) and divalent (MgCl2) inert electrolytes on dispersion properties was
quantified through their contribution to ionic strength. Increasing titania
particle surface area resulted in a decrease in solution pH. At fixed pH,
increasing the particle surface area enhanced the collision frequency between
particles and led to a higher degree of agglomeration. In addition to the
synthesis method, TiO2 isoelectric point was found to be dependent on particle
size. As anatase TiO2 primary particle size increased from 6 nm to 104 nm, its
IEP decreased from 6.0 to 3.8 that also results in changes in dispersion zeta
potential and hydrodynamic size. In contrast to particle size, TiO2 nanoparticle
IEP was found to be insensitive to particle crystal structure.
PMID- 27502651
TI - Effect of Topological Defects on Buckling Behavior of Single-walled Carbon
Nanotube.
AB - Molecular dynamic simulation method has been employed to consider the critical
buckling force, pressure, and strain of pristine and defected single-walled
carbon nanotube (SWCNT) under axial compression. Effects of length, radius,
chirality, Stone-Wales (SW) defect, and single vacancy (SV) defect on buckling
behavior of SWCNTs have been studied. Obtained results indicate that axial
stability of SWCNT reduces significantly due to topological defects. Critical
buckling strain is more susceptible to defects than critical buckling force. Both
SW and SV defects decrease the buckling mode of SWCNT. Comparative approach of
this study leads to more reliable design of nanostructures.
PMID- 27502652
TI - Novel Strategy to Fabricate PLA/Au Nanocomposites as an Efficient Drug Carrier
for Human Leukemia Cells in Vitro.
AB - Poly (lactic acid) (PLA) polymer has the promising applications in the biomedical
field because of its biodegradability and safe elimination. In this study, we
have explored the bio-application of new nanocomposites composed with PLA
nanofibers and Au nanoparticles as the potential drug carrier for an efficient
drug delivery in target cancer cells. The results demonstrated that the
anticancer drug daunorubicin could be efficiently self-assembled on the surface
of PLA/Au nanocomposites and the synergistic enhancement of PLA/Au nanocomposites
conjugated with daunorubicin into drug-sensitive K562 and drug-resistant leukemia
K562/AO2 cells could be obviously observed by MTT assay and confocal fluorescence
microscopy studies. These observations suggest that the new nanocomposites could
readily induce daunorubicin to accumulate and uptake in target leukemia cells and
increase the drug's cytotoxicity. Especially, the PLA/Au nanocomposites could
significantly facilitate the cellular drug absorbtion of daunorubicin into drug
resistant K562/AO2 cells and efficiently inhibit the cancer cell proliferation.
This raised the possibility to utilize the PLA/Au nanocomposites as a new
effective additive agent to inhibit the drug resistance and thus as a novel
strategy to sensitively track the respective cancer cells.
PMID- 27502653
TI - Efficient Performance of Electrostatic Spray-Deposited TiO2 Blocking Layers in
Dye-Sensitized Solar Cells after Swift Heavy Ion Beam Irradiation.
AB - A compact TiO2 layer (~1.1 MUm) prepared by electrostatic spray deposition (ESD)
and swift heavy ion beam (SHI) irradiation using oxygen ions onto a fluorinated
tin oxide (FTO) conducting substrate showed enhancement of photovoltaic
performance in dye-sensitized solar cells (DSSCs). The short circuit current
density (Jsc = 12.2 mA cm(-2)) of DSSCs was found to increase significantly when
an ESD technique was applied for fabrication of the TiO2 blocking layer, compared
to a conventional spin-coated layer (Jsc = 8.9 mA cm(-2)). When SHI irradiation
of oxygen ions of fluence 1 * 10(13) ions/cm(2) was carried out on the ESD TiO2,
it was found that the energy conversion efficiency improved mainly due to the
increase in open circuit voltage of DSSCs. This increased energy conversion
efficiency seems to be associated with improved electronic energy transfer by
increasing the densification of the blocking layer and improving the adhesion
between the blocking layer and the FTO substrate. The adhesion results from
instantaneous local melting of the TiO2 particles. An increase in the electron
transport from the blocking layer may also retard the electron recombination
process due to the oxidized species present in the electrolyte. These findings
from novel treatments using ESD and SHI irradiation techniques may provide a new
tool to improve the photovoltaic performance of DSSCs.
PMID- 27502654
TI - One-Pot Synthesis of Biocompatible CdSe/CdS Quantum Dots and Their Applications
as Fluorescent Biological Labels.
AB - We developed a novel one-pot polyol approach for the synthesis of biocompatible
CdSe quantum dots (QDs) using poly(acrylic acid) (PAA) as a capping ligand at 240
degrees C. The morphological and structural characterization confirmed the
formation of biocompatible and monodisperse CdSe QDs with several nanometers in
size. The encapsulation of CdS thin layers on the surface of CdSe QDs (CdSe/CdS
core-shell QDs) was used for passivating the defect emission (650 nm) and
enhancing the fluorescent quantum yields up to 30% of band-to-band emission (530
600 nm). Moreover, the PL emission peak of CdSe/CdS core-shell QDs could be tuned
from 530 to 600 nm by the size of CdSe core. The as-prepared CdSe/CdS core-shell
QDs with small size, well water solubility, good monodispersity, and bright PL
emission showed high performance as fluorescent cell labels in vitro. The
viability of QDs-labeled 293T cells was evaluated using a 3-(4,5-dimethylthiazol)
2-diphenyltertrazolium bromide (MTT) assay. The results showed the satisfactory
(>80%) biocompatibility of as-synthesized PAA-capped QDs at the Cd concentration
of 15 MUg/ml.
PMID- 27502655
TI - Role of Temperature in the Growth of Silver Nanoparticles Through a Synergetic
Reduction Approach.
AB - This study presents the role of reaction temperature in the formation and growth
of silver nanoparticles through a synergetic reduction approach using two or
three reducing agents simultaneously. By this approach, the shape-/size
controlled silver nanoparticles (plates and spheres) can be generated under mild
conditions. It was found that the reaction temperature could play a key role in
particle growth and shape/size control, especially for silver nanoplates. These
nanoplates could exhibit an intensive surface plasmon resonance in the wavelength
range of 700-1,400 nm in the UV-vis spectrum depending upon their shapes and
sizes, which make them useful for optical applications, such as optical probes,
ionic sensing, and biochemical sensors. A detailed analysis conducted in this
study clearly shows that the reaction temperature can greatly influence reaction
rate, and hence the particle characteristics. The findings would be useful for
optimization of experimental parameters for shape-controlled synthesis of other
metallic nanoparticles (e.g., Au, Cu, Pt, and Pd) with desirable functional
properties.
PMID- 27502656
TI - Characterization of Films with Thickness Less than 10 nm by Sensitivity-Enhanced
Atomic Force Acoustic Microscopy.
AB - We present a method for characterizing ultrathin films using sensitivity-enhanced
atomic force acoustic microscopy, where a concentrated-mass cantilever having a
flat tip was used as a sensitive oscillator. Evaluation was aimed at 6-nm-thick
and 10-nm-thick diamond-like carbon (DLC) films deposited, using different
methods, on a hard disk for the effective Young's modulus defined as E/(1 -
nu(2)), where E is the Young's modulus, and nu is the Poisson's ratio. The
resonant frequency of the cantilever was affected not only by the film's
elasticity but also by the substrate even at an indentation depth of about 0.6
nm. The substrate effect was removed by employing a theoretical formula on the
indentation of a layered half-space, together with a hard disk without DLC
coating. The moduli of the 6-nm-thick and 10-nm-thick DLC films were 392 and 345
GPa, respectively. The error analysis showed the standard deviation less than 5%
in the moduli.
PMID- 27502657
TI - Large-scale Synthesis of beta-SiC Nanochains and Their Raman/Photoluminescence
Properties.
AB - Although the SiC/SiO2 nanochain heterojunction has been synthesized, the chained
homogeneous nanostructure of SiC has not been reported before. Herein, the novel
beta-SiC nanochains are synthesized assisted by the AAO template. The
characterized results demonstrate that the nanostructures are constructed by
spheres of 25-30 nm and conjoint wires of 15-20 nm in diameters. Raman and
photoluminescence measurements are used to explore the unique optical properties.
A speed-alternating vapor-solid (SA-VS) growth mechanism is proposed to interpret
the formation of this typical nanochains. The achieved nanochains enrich the
species of one-dimensional (1D) nanostructures and may hold great potential
applications in nanotechnology.
PMID- 27502658
TI - beta-Phase Morphology in Ordered Poly(9,9-dioctylfluorene) Nanopillars by
Template Wetting Method.
AB - An efficient method based in template wetting is applied for fabrication of
ordered Poly(9,9-dioctylfluorene) (PFO) nanopillars with beta-phase morphology.
In this process, nanoporous alumina obtained by anodization process is used as
template. PFO nanostructures are prepared under ambient conditions via
infiltration of the polymeric solution into the pores of the alumina with an
average pore diameter of 225 nm and a pore depth of 500 nm. The geometric
features of the resulting structures are characterized with environmental
scanning electron microscopy (ESEM), luminescence fluorimeter (PL) and micro MU-X
ray diffractometer (MU-XRD). The characterization demonstrates the beta-phase of
the PFO in the nanopillars fabricated. Furthermore, the PFO nanopillars are
characterized by Raman spectroscopy to study the polymer conformation. These
ordered nanostructures can be used in optoelectronic applications such as polymer
light-emitting diodes, sensors and organic solar cells.
PMID- 27502659
TI - Thermal Effects and Small Signal Modulation of 1.3-MUm InAs/GaAs Self-Assembled
Quantum-Dot Lasers.
AB - We investigate the influence of thermal effects on the high-speed performance of
1.3-MUm InAs/GaAs quantum-dot lasers in a wide temperature range (5-50 degrees
C). Ridge waveguide devices with 1.1 mm cavity length exhibit small signal
modulation bandwidths of 7.51 GHz at 5 degrees C and 3.98 GHz at 50 degrees C.
Temperature-dependent K-factor, differential gain, and gain compression factor
are studied. While the intrinsic damping-limited modulation bandwidth is as high
as 23 GHz, the actual modulation bandwidth is limited by carrier thermalization
under continuous wave operation. Saturation of the resonance frequency was found
to be the result of thermal reduction in the differential gain, which may
originate from carrier thermalization.
PMID- 27502660
TI - Flexible Dye-Sensitized Solar Cell Based on Vertical ZnO Nanowire Arrays.
AB - Flexible dye-sensitized solar cells are fabricated using vertically aligned ZnO
nanowire arrays that are transferred onto ITO-coated poly(ethylene terephthalate)
substrates using a simple peel-off process. The solar cells demonstrate an energy
conversion efficiency of 0.44% with good bending tolerance. This technique paves
a new route for building large-scale cost-effective flexible photovoltaic and
optoelectronic devices.
PMID- 27502661
TI - A High Diffusive Model for Nanomaterials.
AB - Considerable attention is today devoted to the engineering of films widely used
in photocatalytic, solar energy converters, photochemical and
photoelectrochemical cells, dye-sensitized solar cells (DSSCs), to optimize
electronic time response following photogeneration. However, the precise nature
of transport processes in these systems has remained unresolved. To investigate
such aspects of carrier dynamics, we have suggested a model for the calculation
of correlation functions, expressed as the Fourier transform of the frequency
dependent complex conductivity sigma(omega). Results are presented for the
velocity correlation functions, the mean square deviation of position and the
diffusion coefficient in systems, like TiO2 and doped Si, of large interest in
present devices. Fast diffusion occurs in short time intervals of the order of
few collision times. Consequences for efficiency of this fast response are
discussed in relation to nanostructured devices.
PMID- 27502662
TI - Investigation on the Plasma-Induced Emission Properties of Large Area Carbon
Nanotube Array Cathodes with Different Morphologies.
AB - Large area well-aligned carbon nanotube (CNT) arrays with different morphologies
were synthesized by using a chemical vapor deposition. The plasma-induced
emission properties of CNT array cathodes with different morphologies were
investigated. The ratio of CNT height to CNT-to-CNT distance has considerable
effects on their plasma-induced emission properties. As the ratio increases,
emission currents of CNT array cathodes decrease due to screening effects. Under
the pulse electric field of about 6 V/MUm, high-intensity electron beams of 170
180 A/cm(2) were emitted from the surface plasma. The production mechanism of the
high-intensity electron beams emitted from the CNT arrays was plasma-induced
emission. Moreover, the distribution of the electron beams was in situ
characterized by the light emission from the surface plasma.
PMID- 27502663
TI - Nano-Floating Gate Memory Devices Composed of ZnO Thin-Film Transistors on
Flexible Plastics.
AB - Nano-floating gate memory devices were fabricated on a flexible plastic substrate
by a low-temperature fabrication process. The memory characteristics of ZnO-based
thin-film transistors with Al nanoparticles embedded in the gate oxides were
investigated in this study. Their electron mobility was found to be 0.18
cm(2)/V.s and their on/off ratio was in the range of 10(4)-10(5). The threshold
voltages of the programmed and erased states were negligibly changed up to 10(3)
cycles. The flexibility, memory properties, and low-temperature fabrication of
the nano-floating gate memory devices described herein suggest that they have
potential applications for future flexible integrated electronics.
PMID- 27502664
TI - The Investigation of Intermediate Stage of Template Etching with Metal Droplets
by Wetting Angle Analysis on (001) GaAs Surface.
AB - In this work, we study metal droplets on a semiconductor surface that are the
initial stage for both droplet epitaxy and local droplet etching. The
distributions of droplet geometrical parameters such as height, radius and volume
help to understand the droplet formation that strongly influences subsequent
nanohole etching. To investigate the etching and intermixing processes, we offer
a new method of wetting angle analysis. The aspect ratio that is defined as the
ratio of the height to radius was used as an estimation of wetting angle which
depends on the droplet material. The investigation of the wetting angle and the
estimation of indium content revealed significant materials intermixing during
the deposition time. AFM measurements reveal the presence of two droplet groups
that is in agreement with nanohole investigations. To explain this observation,
we consider arsenic evaporation and consequent change in the initial substrate.
On the basis of our analysis, we suggest the model of droplet evolution and the
formation of two droplet groups.
PMID- 27502665
TI - Trapping Iron Oxide into Hollow Gold Nanoparticles.
AB - Synthesis of the core/shell-structured Fe3O4/Au nanoparticles by trapping Fe3O4
inside hollow Au nanoparticles is described. The produced composite nanoparticles
are strongly magnetic with their surface plasmon resonance peaks in the near
infrared region (wavelength from 700 to 800 nm), combining desirable magnetic and
plasmonic properties into one nanoparticle. They are particularly suitable for in
vivo diagnostic and therapeutic applications. The intact Au surface provides
convenient anchorage sites for attachment of targeting molecules, and the
particles can be activated by both near infrared lights and magnetic fields. As
more and more hollow nanoparticles become available, this synthetic method would
find general applications in the fabrication of core-shell multifunctional
nanostructures.
PMID- 27502666
TI - Single Walled Carbon Nanotubes Exhibit Dual-Phase Regulation to Exposed
Arabidopsis Mesophyll Cells.
AB - Herein we are the first to report that single-walled carbon nanotubes (SWCNTs)
exhibit dual-phase regulation to Arabidopsis mesophyll cells exposed to different
concentration of SWCNTs. The mesophyll protoplasts were prepared by enzyme
digestion, and incubated with 15, 25, 50, 100 MUg/ml SWCNTs for 48 h, and then
were observed by optical microscopy and transmission electron microscopy, the
reactive oxygen species (ROS) generation was measured. Partial protoplasts were
stained with propidium iodide and 4'-6- diamidino-2-phenylindole, partial
protoplasts were incubated with fluorescein isothiocyanate-labeled SWCNTs, and
observed by fluorescence microscopy. Results showed that SWCNTs could traverse
both the plant cell wall and cell membrane, with less than or equal to 50 MUg/ml
in the culture medium, SWCNTs stimulated plant cells to grow out trichome
clusters on their surface, with more than 50 MUg/ml SWCNTs in the culture medium,
SWCNTs exhibited obvious toxic effects to the protoplasts such as increasing
generation of ROS, inducing changes of protoplast morphology, changing green
leaves into yellow, and inducing protoplast cells' necrosis and apoptosis. In
conclusion, single walled carbon nanotubes can get through Arabidopsis mesophyll
cell wall and membrane, and exhibit dose-dependent dual-phase regulation to
Arabidopsis mesophyll protoplasts such as low dose stimulating cell growth, and
high dose inducing cells' ROS generation, necrosis or apoptosis.
PMID- 27502667
TI - A Novel Way for Synthesizing Phosphorus-Doped Zno Nanowires.
AB - We developed a novel approach to synthesize phosphorus (P)-doped ZnO nanowires by
directly decomposing zinc phosphate powder. The samples were demonstrated to be P
doped ZnO nanowires by using scanning electron microscopy, high-resolution
transmission electron microscopy, X-ray diffraction spectra, X-ray photoelectron
spectroscopy, energy dispersive spectrum, Raman spectra and photoluminescence
measurements. The chemical state of P was investigated by electron energy loss
spectroscopy (EELS) analyses in individual ZnO nanowires. P was found to
substitute at oxygen sites (PO), with the presence of anti-site P on Zn sites
(PZn). P-doped ZnO nanowires were high resistance and the related P-doping
mechanism was discussed by combining EELS results with electrical measurements,
structure characterization and photoluminescence measurements. Our method
provides an efficient way of synthesizing P-doped ZnO nanowires and the results
help to understand the P-doping mechanism.
PMID- 27502669
TI - Highly Efficient Method for Preparing Homogeneous and Stable Colloids Containing
Graphene Oxide.
AB - Phase transfer method has been developed for preparing homogeneous and stable
graphene oxide colloids. Graphene oxide nanosheets (GONs) were successfully
transferred from water to n-octane after modification by oleylamine. Corrugation
and scrolling exist dominantly in the modified GONs. GONs were single layered
with the maximum solubility in n-octane up to 3.82 mg mL(-1). Oleylamine
molecules chemically attach onto the GONs. Compared with traditional strategies,
the phase transfer method has the features of simplicity and high efficiency.
PMID- 27502668
TI - Observation of Coalescence Process of Silver Nanospheres During Shape
Transformation to Nanoprisms.
AB - In this report, we observed the growth mechanism and the shape transformation
from spherical nanoparticles (diameter ~6 nm) to triangular nanoprisms (bisector
length ~100 nm). We used a simple direct chemical reduction method and provided
evidences for the growth of silver nanoprisms via a coalescence process. Unlike
previous reports, our method does not rely upon light, heat, or strong oxidant
for the shape transformation. This transformation could be launched by fine
tuning the pH value of the silver colloidal solution. Based on our extensive
examination using transmission electron microscopy, we propose a non-point
initiated growth mechanism, which is a combination of coalescence and dissolution
recrystallization process during the growth of silver nanoprisms.
PMID- 27502670
TI - Dielectric Relaxation of La-Doped Zirconia Caused by Annealing Ambient.
AB - La-doped zirconia films, deposited by ALD at 300 degrees C, were found to be
amorphous with dielectric constants (k-values) up to 19. A tetragonal or cubic
phase was induced by post-deposition annealing (PDA) at 900 degrees C in both
nitrogen and air. Higher k-values (~32) were measured following PDA in air, but
not after PDA in nitrogen. However, a significant dielectric relaxation was
observed in the air-annealed film, and this is attributed to the formation of
nano-crystallites. The relaxation behavior was modeled using the Curie-von
Schweidler (CS) and Havriliak-Negami (HN) relationships. The k-value of the as
deposited films clearly shows a mixed CS and HN dependence on frequency. The CS
dependence vanished after annealing in air, while the HN dependence disappeared
after annealing in nitrogen.
PMID- 27502671
TI - Nanospiral Formation by Droplet Drying: One Molecule at a Time.
AB - We have created nanospirals by self-assembly during droplet evaporation. The
nanospirals, 60-70 nm in diameter, formed when solvent mixtures of methanol and m
cresol were used. In contrast, spin coating using only methanol as the solvent
produced epitaxial films of stripe nanopatterns and using only m-cresol
disordered structure. Due to the disparity in vapor pressure between the two
solvents, droplets of m-cresol solution remaining on the substrate serve as
templates for the self-assembly of carboxylic acid molecules, which in turn
allows the visualization of solution droplet evaporation one molecule at a time.
PMID- 27502672
TI - Determination of InN/Diamond Heterojunction Band Offset by X-ray Photoelectron
Spectroscopy.
AB - Diamond is not only a free standing highly transparent window but also a
promising carrier confinement layer for InN based devices, yet little is known of
the band offsets in InN/diamond system. X-ray photoelectron spectroscopy was used
to measure the energy discontinuity in the valence band offset (VBO) of
InN/diamond heterostructure. The value of VBO was determined to be 0.39 +/- 0.08
eV and a type-I heterojunction with a conduction band offset (CBO) of 4.42 +/-
0.08 eV was obtained. The accurate determination of VBO and CBO is important for
the application of III-N alloys based electronic devices.
PMID- 27502673
TI - Enhanced Specificity of Multiplex Polymerase Chain Reaction via CdTe Quantum
Dots.
AB - Nanoparticles were recently reported to be able to improve both efficiency and
specificity in polymerase chain reaction (PCR). Here, CdTe QDs were introduced
into multi-PCR systems. It was found that an appropriate concentration of CdTe
QDs could enhance the performance of multi-PCR by reducing the formation of
nonspecific products in the complex system, but an excessive amount of CdTe QDs
could suppress the PCR. The effects of QDs on PCR can be reversed by increasing
the polymerase concentration or by adding bovine serum albumin (BSA). The
mechanisms underlying these effects were also discussed. The results indicated
that CdTe QDs could be used to optimize the amplification products of the PCR,
especially in the multi-PCR system with different primers annealing temperatures,
which is of great significance for molecular diagnosis.
PMID- 27502674
TI - Giant Persistent Photoconductivity of the WO3 Nanowires in Vacuum Condition.
AB - A giant persistent photoconductivity (PPC) phenomenon has been observed in vacuum
condition based on a single WO3 nanowire and presents some interesting results in
the experiments. With the decay time lasting for 1 * 10(4) s, no obvious current
change can be found in vacuum, and a decreasing current can be only observed in
air condition. When the WO3 nanowires were coated with 200 nm SiO2 layer, the
photoresponse almost disappeared. And the high bias and high electric field
effect could not reduce the current in vacuum condition. These results show that
the photoconductivity of WO3 nanowires is mainly related to the oxygen adsorption
and desorption, and the semiconductor photoconductivity properties are very weak.
The giant PPC effect in vacuum condition was caused by the absence of oxygen
molecular. And the thermal effect combining with oxygen re-adsorption can reduce
the intensity of PPC.
PMID- 27502675
TI - Radial Corrugations of Multi-Walled Carbon Nanotubes Driven by Inter-Wall
Nonbonding Interactions.
AB - We perform large-scale quasi-continuum simulations to determine the stable cross
sectional configurations of free-standing multi-walled carbon nanotubes (MWCNTs).
We show that at an inter-wall spacing larger than the equilibrium distance set by
the inter-wall van der Waals (vdW) interactions, the initial circular cross
sections of the MWCNTs are transformed into symmetric polygonal shapes or
asymmetric water-drop-like shapes. Our simulations also show that removing
several innermost walls causes even more drastic cross-sectional polygonization
of the MWCNTs. The predicted cross-sectional configurations agree with prior
experimental observations. We attribute the radial corrugations to the
compressive stresses induced by the excessive inter-wall vdW energy release of
the MWCNTs. The stable cross-sectional configurations provide fundamental
guidance to the design of single MWCNT-based devices and shed lights on the
mechanical control of electrical properties.
PMID- 27502676
TI - Atomic Force Microscopy Study of Protein-Protein Interactions in the Cytochrome
CYP11A1 (P450scc)-Containing Steroid Hydroxylase System.
AB - Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) were used
for monitoring of the procedure for cytochrome CYP11A1 monomerization in solution
without phospholipids. It was shown that the incubation of 100 MUM CYP11A1 with
12% Emulgen 913 in 50 mM KP, pH 7.4, for 10 min at T = 22 degrees C leads to
dissociation of hemoprotein aggregates to monomers with the monomerization degree
of (82 +/- 4)%. Following the monomerization procedure, CYP11A1 remained
functionally active. AFM was employed to detect and visualize the isolated
proteins as well as complexes formed between the components of the cytochrome
CYP11A1-dependent steroid hydroxylase system. Both Ad and AdR were present in
solution as monomers. The typical heights of the monomeric AdR, Ad and CYP11A1
images were measured by AFM and were found to correspond to the sizes 1.6 +/- 0.2
nm, 1.0 +/- 0.2 nm and 1.8 +/- 0.2 nm, respectively. The binary Ad/AdR and
AdR/CYP11A1mon complexes with the heights 2.2 +/- 0.2 nm and 2.8 +/- 0.2 nm,
respectively, were registered by use of AFM. The Ad/CYP11A1mon complex formation
reaction was kinetically characterized based on optical biosensor data. In
addition, the ternary AdR/Ad/CYP11A1 complexes with a typical height of 4 +/- 1
nm were AFM registered.
PMID- 27502677
TI - The Microscopic Origin of Residual Stress for Flat Self-Actuating Piezoelectric
Cantilevers.
AB - In this study, flat piezoelectric microcantilevers were fabricated under low
stress Pb(Zr0.52Ti0.48)O3 (PZT) film conditions. They were analyzed using the
Raman spectrum and wafer curvature methods. Based on the residual stress
analysis, we found that a thickness of 1 MUm was critical, since stress
relaxation starts to occur at greater thicknesses, due to surface roughening. The
(111) preferred orientation started to decrease when the film thickness was
greater than 1 MUm. The d33 value was closely related to the stress relaxation
associated with the preferred orientation changes. We examined the harmonic
response at different PZT cantilever lengths and obtained a 9.4-MUm tip
displacement at 3 Vp-p at 1 kHz. These analyses can provide a platform for the
reliable operation of piezoelectric microdevices, potentially nanodevice when one
needs to have simultaneous control of the residual stress and the piezoelectric
properties.
PMID- 27502679
TI - Synthesis and Thermoelectric Properties of Bi2Se3 Nanostructures.
AB - Bismuth selenide (Bi2Se3) nanostructures were synthesized via solvothermal
method. The crystallinity of the as-synthesized sample has been analyzed by X-ray
diffraction, which shows the formation of rhombohedral Bi2Se3. Electron
microscopy examination indicates that the Bi2Se3 nanoparticles have hexagonal
flake-like shape. The effect of the synthesis temperature on the morphology of
the Bi2Se3 nanostructures has also been investigated. It is found that the
particle size increases with the synthesis temperature. Thermoelectric properties
of the Bi2Se3 nanostructures were also measured, and the maximum value of
dimensionless figure of merit (ZT) of 0.096 was obtained at 523 K.
PMID- 27502678
TI - Anisotropic Confinement, Electronic Coupling and Strain Induced Effects Detected
by Valence-Band Anisotropy in Self-Assembled Quantum Dots.
AB - A method to determine the effects of the geometry and lateral ordering on the
electronic properties of an array of one-dimensional self-assembled quantum dots
is discussed. A model that takes into account the valence-band anisotropic
effective masses and strain effects must be used to describe the behavior of the
photoluminescence emission, proposed as a clean tool for the characterization of
dot anisotropy and/or inter-dot coupling. Under special growth conditions, such
as substrate temperature and Arsenic background, 1D chains of In0.4Ga0.6 As
quantum dots were grown by molecular beam epitaxy. Grazing-incidence X-ray
diffraction measurements directly evidence the strong strain anisotropy due to
the formation of quantum dot chains, probed by polarization-resolved low
temperature photoluminescence. The results are in fair good agreement with the
proposed model.
PMID- 27502680
TI - Template-free Synthesis of One-dimensional Cobalt Nanostructures by Hydrazine
Reduction Route.
AB - One-dimensional cobalt nanostructures with large aspect ratio up to 450 have been
prepared via a template-free hydrazine reduction route under external magnetic
field assistance. The morphology and properties of cobalt nanostructures were
characterized by scanning electron microscopy, X-ray diffractometer, and
vibrating sample magnetometer. The roles of the reaction conditions such as
temperature, concentration, and pH value on morphology and magnetic properties of
fabricated Co nanostructures were investigated. This work presents a simple, low
cost, environment-friendly, and large-scale production approach to fabricate one
dimensional magnetic Co materials. The resulting materials may have potential
applications in nanodevice, catalytic agent, and magnetic recording.
PMID- 27502681
TI - Formation of Nanopits in Si Capping Layers on SiGe Quantum Dots.
AB - In-situ annealing at a high temperature of 640 degrees C was performed for a low
temperature grown Si capping layer, which was grown at 300 degrees C on SiGe self
assembled quantum dots with a thickness of 50 nm. Square nanopits, with a depth
of about 8 nm and boundaries along <110>, are formed in the Si capping layer
after annealing. Cross-sectional transmission electron microscopy observation
shows that each nanopit is located right over one dot with one to one
correspondence. The detailed migration of Si atoms for the nanopit formation is
revealed by in-situ annealing at a low temperature of 540 degrees C. The final
well-defined profiles of the nanopits indicate that both strain energy and
surface energy play roles during the nanopit formation, and the nanopits are
stable at 640 degrees C. A subsequent growth of Ge on the nanopit-patterned
surface results in the formation of SiGe quantum dot molecules around the
nanopits.
PMID- 27502682
TI - In Situ Synthesis of Reduced Graphene Oxide and Gold Nanocomposites for
Nanoelectronics and Biosensing.
AB - In this study, an in situ chemical synthesis approach has been developed to
prepare graphene-Au nanocomposites from chemically reduced graphene oxide (rGO)
in aqueous media. UV-Vis absorption, atomic force microscopy, scanning electron
microscopy, transmission electron microscopy, and Raman spectroscopy were used to
demonstrate the successful attachment of Au nanoparticles to graphene sheets.
Configured as field-effect transistors (FETs), the as-synthesized single-layered
rGO-Au nanocomposites exhibit higher hole mobility and conductance when compared
to the rGO sheets, promising its applications in nanoelectronics. Furthermore, we
demonstrate that the rGO-Au FETs are able to label-freely detect DNA
hybridization with high sensitivity, indicating its potentials in nanoelectronic
biosensing.
PMID- 27502683
TI - Conductance of Graphene Nanoribbon Junctions and the Tight Binding Model.
AB - Planar carbon-based electronic devices, including metal/semiconductor junctions,
transistors and interconnects, can now be formed from patterned sheets of
graphene. Most simulations of charge transport within graphene-based electronic
devices assume an energy band structure based on a nearest-neighbour tight
binding analysis. In this paper, the energy band structure and conductance of
graphene nanoribbons and metal/semiconductor junctions are obtained using a third
nearest-neighbour tight binding analysis in conjunction with an efficient
nonequilibrium Green's function formalism. We find significant differences in
both the energy band structure and conductance obtained with the two
approximations.
PMID- 27502684
TI - Effect of MWCNTs on Gastric Emptying in Mice.
AB - After making model of gastric functional disorder (FD), part of model mice were
injected intravenously (i.v.) with oxide multi-walled carbon nanotubes (oMWCNTs)
to investigate effect of carbon nanotubes on gastric emptying. The results showed
that NO content in stomach, compared with model group, was decreased
significantly and close to normal level post-injection with oMWCNTs (500 and 800
MUg/mouse). In contrast to FD or normal groups, the content of acetylcholine
(Ach) in stomach was increased obviously in injection group with 500 or 800
MUg/mouse of oMWCNTs. The kinetic curve of emptying was fitted to calculate
gastric motility factor k; the results showed that the k of injection group was
much higher than FD and normal. In other words, the gastric motility of FD mice
was enhanced via injection with oMWCNTs. In certain dosage, oMWCNTs could improve
gastric emptying and motility.
PMID- 27502685
TI - Morphology and Microstructure of As-Synthesized Anodic TiO2 Nanotube Arrays.
AB - The as-grown structure of electrochemically synthesized titania nanotube arrays
is investigated by scanning electron microscope (SEM) in combination with
transmission electron microscope (TEM) as well as X-ray diffraction (XRD). The
analysis reveals a preferred growth direction of the nanotubes relative to the
substrate surface and the well control on the nanotube arrays morphology. The
crystal structure of the anatase phase is detected and exists in the tube walls
without any thermal treatment, which makes it possible to realize the application
of as-formed TiO2 nanotubes avoiding the degradation of the nanotube structures
when sintering. In addition, a new growth, layered model of the anodic TiO2
nanotubes is presented to obtain further understanding of the growth mechanism.
PMID- 27502686
TI - n-Type Doping of Vapor-Liquid-Solid Grown GaAs Nanowires.
AB - In this letter, n-type doping of GaAs nanowires grown by metal-organic vapor
phase epitaxy in the vapor-liquid-solid growth mode on (111)B GaAs substrates is
reported. A low growth temperature of 400 degrees C is adjusted in order to
exclude shell growth. The impact of doping precursors on the morphology of GaAs
nanowires was investigated. Tetraethyl tin as doping precursor enables heavily n
type doped GaAs nanowires in a relatively small process window while no doping
effect could be found for ditertiarybutylsilane. Electrical measurements carried
out on single nanowires reveal an axially non-uniform doping profile. Within a
number of wires from the same run, the donor concentrations ND of GaAs nanowires
are found to vary from 7 * 10(17) cm(-3) to 2 * 10(18) cm(-3). The n-type
conductivity is proven by the transfer characteristics of fabricated nanowire
metal-insulator-semiconductor field-effect transistor devices.
PMID- 27502687
TI - Mathematical modelling of the degradation behaviour of biodegradable metals.
AB - A mathematical model for the biodegradation of magnesium is developed in this
study to inspect the corrosion behaviour of biodegradable implants. The aim of
this study was to provide a suitable framework for the assessment of the
corrosion rate of magnesium which includes the process of formation/dissolution
of the protective film. The model is intended to aid the design of implants with
suitable geometries. The level-set method is used to follow the changing geometry
of the implants during the corrosion process. A system of partial differential
equations is formulated based on the physical and chemical processes that occur
at the implant-medium boundary in order to simulate the effect of the formation
of a protective film on the degradation rate. The experimental data from the
literature on the corrosion of a high-purity magnesium sample immersed in
simulated body fluid is used to calibrate the model. The model is then used to
predict the degradation behaviour of a porous orthopaedic implant. The model
successfully reproduces the precipitation of the corrosion products on the
magnesium surface and the effect on the degradation rate. It can be used to
simulate the implant degradation and the formation of the corrosion products on
the surface of biodegradable magnesium implants with complex geometries.
PMID- 27502688
TI - Regulation of autophagy by mitochondrial phospholipids in health and diseases.
AB - Autophagy is an evolutionarily conserved mechanism that maintains nutrient
homeostasis by degrading protein aggregates and damaged organelles. Autophagy is
reduced in aging, which is implicated in the pathogenesis of aging-related
diseases, including cancers, obesity, type 2 diabetes, cardiovascular diseases,
and neurodegenerative diseases. Mitochondria-derived phospholipids cardiolipin,
phosphatidylethanolamine, and phosphatidylglycerol are critical throughout the
autophagic process, from initiation and phagophore formation to elongation and
fusion with endolysosomal vesicles. Cardiolipin is also required for
mitochondrial fusion and fission, an important step in isolating dysfunctional
mitochondria for mitophagy. Furthermore, genetic screen in yeast has identified a
surprising role for cardiolipin in regulating lysosomal function.
Phosphatidylethanolamine plays a pivotal role in supporting the autophagic
process, including autophagosome elongation as part of lipidated Atg8/LC3. An
emerging role for phosphatidylglycerol in AMPK and mTORC1 signaling as well as
mitochondrial fission may provide the first glimpse into the function of
phosphatidylglycerol apart from being a precursor for cardiolipin. This review
examines the effects of manipulating phospholipids on autophagy and mitophagy in
health and diseases, as well as current limitations in the field. This article is
part of a Special Issue entitled: Lipids of Mitochondria edited by Guenther Daum.
PMID- 27502689
TI - Factors associated with poor adherence to antiviral treatment for hepatitis B.
AB - Antiviral therapy for hepatitis B is effective and reduces the risk of
progression to cirrhosis and liver cancer but is often required for an indefinite
duration. Treatment adherence is important to prevent the development of
resistance and optimize outcomes. Pharmacy adherence measures can be used to
assess treatment adherence, with the medication possession ratio being less
susceptible to bias than physician- or self-reported adherence. The aim of this
study was to measure adherence in public hospital outpatients over a 3-year
period and to examine factors associated with nonadherence. A retrospective study
of pharmacy records of patients dispensed antiviral therapy for hepatitis B from
four major hospitals in Melbourne between 2010 and 2013. Hospital record numbers
were linked with and de-identified demographic information including age, sex,
Indigenous status, country of birth, interpreter requirement, spoken language and
postcode of residence. The medication possession ratio was the outcome measure
with poor adherence defined <.90. Univariate logistic regression and multivariate
logistic regression were performed to examine associations with nonadherence.
Records of 1026 patients were included in the analysis. Twenty per cent of all
participants met the definition of poor adherence. Significant factors affecting
adherence included age <35 years (P=.002), hospital site and treatment by
multiple doctors within shorter time periods. This is the largest study examining
detailed factors associated with adherence to hepatitis B treatment.
Understanding poor adherence in clinical settings, and the factors associated
with lower adherence, is important to inform efforts towards promoting treatment
adherence for hepatitis B.
PMID- 27502690
TI - Promotion of couples' voluntary HIV counseling and testing: a comparison of
influence networks in Rwanda and Zambia.
AB - BACKGROUND: Many African adults do not know that partners in steady or cohabiting
relationships can have different HIV test results. Despite WHO recommendations
for couples' voluntary counseling and testing (CVCT), fewer than 10 % of couples
have been jointly tested and counseled. We examine the roles and interactions of
influential network leaders (INLs) and influential network agents (INAs) in
promoting CVCT in Kigali, Rwanda and Lusaka, Zambia. METHODS: INLs were
identified in the faith-based, non-governmental, private, and health sectors.
Each INL recruited and mentored several INAs who promoted CVCT. INLs and INAs
were interviewed about demographic characteristics, promotional efforts, and
working relationships. We also surveyed CVCT clients about sources of CVCT
information. RESULTS: In Zambia, 53 INAs and 31 INLs were surveyed. In Rwanda, 33
INAs and 27 INLs were surveyed. Most (75 %-90 %) INAs believed that INL support
was necessary for their promotional work. Zambian INLs reported being more
engaged with their INAs than Rwandan INLs, with 58 % of Zambian INLs reporting
that they gave a lot of support to their INAs versus 39 % in Rwanda. INAs in both
Rwanda and Zambia reported promoting CVCT via group forums (77 %-97 %) and
speaking to a community leader about CVCT (79 %-88 %) in the past month. More
Rwandan INAs and INLs reported previous joint or individual HIV testing compared
with their Zambian counterparts, of which more than half had not been tested. In
Zambia and Rwanda, 1271 and 3895 CVCT clients were surveyed, respectively.
Hearing about CVCT from INAs during one-on-one promotions was the most frequent
source of information reported by clients in Zambia (71 %). In contrast, Rwandan
couples who tested were more likely to have heard about CVCT from a previously
tested couple (59 %). CONCLUSIONS: CVCT has long been endorsed for HIV prevention
but few couples have been reached. Influential social networks can successfully
promote evidence-based HIV prevention in Africa. Support from more senior INLs
and group presentations leveraged INAs' one-on-one promotions. The INL/INA model
was effective in promoting couples to seek joint HIV testing and counseling and
may have broader application to other sub-Saharan African countries to
sustainably increase CVCT uptake.
PMID- 27502691
TI - Cognitive leisure activities and future risk of cognitive impairment and
dementia: systematic review and meta-analysis.
AB - BACKGROUND: As life expectancies continue to rise, modifiable lifestyle factors
that may prevent cognitive decline and dementia in later life become increasingly
important in order to maintain quality of life in old age. METHODS: Five meta
analyses were conducted on data from papers identified in a systematic review.
Studies were grouped according to outcomes (dementia, cognitive impairment
including amnestic Mild Cognitive Impairment (aMCI), Mild Cognitive Impairment
(MCI), and cognitive decline) and output (risk (RR), odds (OR), or hazard ratios
(HR)). RESULTS: Nineteen studies met our inclusion criteria and quality
assessments. Four of five meta-analyses showed significant associations between
participation in cognitive leisure activities and reduced risk of cognitive
impairment (OR = 0.69, 95% CI: 0.56-0.85) and dementia (HR = 0.58, 95% CI: 0.46
0.74; RR = 0.61, 95% CI: 0.42-0.90; OR = 0.78, 95% CI: 0.67-0.90). However, one
pooled analysis of cognitive impairment studies did not reach significance (HR =
0.85, 95% CI: 0.71-1.02). Mentally stimulating leisure activities were
significantly associated with later life cognition (beta = 0.11, p = 0.05),
better memory (beta = 0.20, 95% CI: 0.11-0.29), speed of processing (beta = 0.37,
95% CI: 0.29-0.45), and executive functioning (beta = 0.23, 95% CI: 0.15-0.29),
and less decline in overall cognition (beta = -0.23, p < 0.01), language (beta =
0.11, p < 0.05), and executive functioning (beta = -0.13, p < 0.05). Activities
were also shown to reduce rate of cognitive decline (estimate = 0.03, SE = 0.01,
p = 0.00). CONCLUSIONS: There is increasing evidence that participation in
cognitively stimulating leisure activities may contribute to a reduction of risk
of dementia and cognitive impairment in later life. Promoting involvement in such
activities across lifespan could be an important focus for primary prevention
strategies for governments and health services.
PMID- 27502692
TI - Preference in time of insulin injection in type 2 diabetic patients treated with
once-daily long-acting insulin analog.
PMID- 27502693
TI - Fine mapping and genetic association analysis of Net2, the causative D-genome
locus of low temperature-induced hybrid necrosis in interspecific crosses between
tetraploid wheat and Aegilops tauschii.
AB - Hybrid necrosis has been observed in many interspecific hybrids from crosses
between tetraploid wheat and the wheat D-genome donor Aegilops tauschii. Type II
necrosis is a kind of hybrid incompatibility that is specifically characterized
by low-temperature induction and growth suppression. Two complementary genes,
Net1 on the AB genome and Net2 on the D genome, putatively control type II
necrosis in ABD triploids and synthetic hexaploid wheat. Toward map-based cloning
of Net2, a fine map around the Net2 region on 2DS was constructed in this study.
Using the draft genome sequence of Ae. tauschii and the physical map of the
barley genome, the Net2 locus was mapped within a 0.6 cM interval between two
closely linked markers. Although local chromosomal rearrangements were observed
in the Net2-corresponding region between the barley/Brachypodium and Ae. tauschii
genomes, the two closely linked markers were significantly associated with type
II necrosis in Ae. tauschii. These results suggest that these markers will aid
efficient selection of Net2 non-carrier individuals from the Ae. tauschii
population and intraspecific progeny, and could help with introgression of
agriculturally important genes from Ae. tauschii to common wheat.
PMID- 27502694
TI - Mycoplasma genitalium macrolide resistance in Stockholm, Sweden.
AB - OBJECTIVES: Mycoplasma genitalium is an important cause of STI in men and women.
Worldwide evidence suggests a reduction in efficacy of azithromycin treatment due
to the prevalence of macrolide resistant M. genitalium. The aim of this study was
to describe the prevalence of macrolide resistance in patients with a positive
test for M. genitalium within our setting. METHODS: Two STI clinics in Stockholm
offered tests for M. genitalium as part of a routine care pathway. Positive
specimens were analysed for macrolide resistance mediating mutations by
sequencing. RESULTS: During the study period, 171 (7.5%) of 2276 patients had a
positive M. genitalium test; 7% of women and 8% of men. Macrolide resistance was
detected in 31 (18%) of the M. genitalium positive; treatment with azithromycin
within the previous 6 months was strongly associated with macrolide resistance.
CONCLUSIONS: The prevalence of macrolide resistance was lower in Sweden than in
other Northern European settings. We hypothesise that this observation may be due
to use of doxycycline as primary treatment of Chlamydia trachomatis. The efficacy
of empirical treatment is challenged by azithromycin resistant M. genitalium.
Clinically available and enhanced diagnostics targeting this pathogen are
urgently required. We suggest a test of cure 3-4 weeks after start of
azithromycin therapy since macrolide resistance develop during treatment.
PMID- 27502695
TI - STAT3-mediated TLR2/4 pathway upregulation in an IFN-gamma-induced Chlamydia
trachomatis persistent infection model.
AB - Inflammatory pathological injury caused by Chlamydia trachomatis persistent
infection could lead to a variety of urogenital tract diseases. By comparing the
cytokine production and PRR (pattern recognition receptor) expression between
cell models with acute or persistent C. trachomatis infection, our data supported
that persistent infection of C. trachomatis led to abnormal activation of toll
like receptor (TLR)2/4 signaling pathway and elevated IL-1alpha and IL-6
production, which was mediated by signal transducer and activator of
transcription3 (STAT3). Studying the effects of abnormal activation of TLR
signaling pathway in the cells with C. trachomatis persistent infection could
provide new hints for chronic infection treatment and an important experimental
basis for understanding the pathogenesis of C. trachomatis persistent infection.
PMID- 27502697
TI - Imaginaries of nuclear energy in the Portuguese parliament: Between promise,
risk, and democracy.
AB - This article explores the evolution of the nuclear energy debate and its
associated controversies in the Portuguese parliament. The analysis focuses on
the dictatorial regime of the New State (from the beginning of the nuclear
program in 1951 until the 1974 revolution) and on the democratic period (post
1974). Portugal, as an exporting country of uranium minerals, significantly
invested in the development of a national capacity in nuclear research, but never
developed an endogenous nuclear power infrastructure. Through the analysis of
parliamentary debates, this article characterizes the dynamic evolution of the
Portuguese sociotechnical imaginary on nuclear energy and technology interlinked
with ambivalent representations, including the promise of nuclear energy as key
for the constitution of a technological Nation or as prompting new sociotechnical
risks.
PMID- 27502696
TI - Intravenous adenovirus expressing a multi-specific, single-domain antibody
neutralizing TcdA and TcdB protects mice from Clostridium difficile infection.
AB - Clostridium difficile infection (CDI) is the most common cause of antibiotic
associated diarrhea and colitis in developed countries. The disease is mainly
mediated via two major exotoxins TcdA and TcdB secreted by the bacterium. We have
previously developed a novel, potently neutralizing, tetravalent and bispecific
heavy-chain-only single domain (VHH) antibody to both TcdA and TcdB (designated
as ABA) that reverses fulminant CDI in mice. Since ABA has a short serum half
life, in this study a replication-deficient recombinant adenovirus expressing ABA
was generated and the long-lasting expression of functional ABA was demonstrated
in vitro and in vivo Mice transduced with one dose of the adenovirus displayed
high levels of serum ABA for more than1 month and were fully protected against
systemic toxin challenges. More importantly, the ABA delivered by the adenovirus
protected mice from both primary and recurrent CDI. Thus, replication-deficient
adenoviral vector may be used to deliver neutralizing antibodies against the
toxins in order to prevent CDI and recurrence.
PMID- 27502698
TI - Radial simultaneous multi-slice CAIPI for ungated myocardial perfusion.
AB - OBJECTIVE: Simultaneous multi-slice (SMS) imaging is a slice acceleration
technique that acquires multiple slices in the same time as a single slice.
Radial controlled aliasing in parallel imaging results in higher acceleration
(radial CAIPIRINHA or CAIPI) is a promising SMS method with less severe slice
aliasing artifacts as compared to its Cartesian counterpart. Here we use radial
CAIPI with data undersampling and constrained reconstruction to improve the
utility of ungated cardiac perfusion acquisitions. We test the proposed framework
with a traditional saturation recovery fast low-angle shot (turboFLASH) sequence
and also without saturation recovery as a steady-state spoiled gradient echo
(SPGR) sequence on animal and human studies. METHODS: Simulations and phantom
studies were performed for both the turboFLASH and the SPGR radial CAIPI methods.
Ungated undersampled golden ratio radial CAIPI data with saturation recovery were
acquired in 8 dogs and 2 human subjects. The CAIPI data without saturation pulses
were acquired in 4 human subjects. For both methods, slice acceleration factors
of two and three were used. A new spatio-temporal reconstruction using total
variation and patch-based low rank constraints was used to jointly reconstruct
the multi-slice multi-coil images. RESULTS: Phantom scans and computer
simulations showed that ungated SPGR generally provides better contrast to noise
ratio (CNR) than the saturation recovery sequence if the saturation recovery time
is less than 100ms. Both of the ungated radial CAIPI methods demonstrated
promising image quality in terms of preserving dynamics of the contrast agent and
maintaining anatomical structures, even with three slices acquired
simultaneously. CONCLUSION: Ungated simultaneous multi-slice acquisitions with
either a saturation recovery turboFLASH sequence or a steady-state gradient echo
SPGR sequence are feasible and provide increased slice coverage without loss of
temporal resolution. Compared with a sensitivity encoding (SENSE) SMS
reconstruction, the constrained reconstruction method provides better image
quality for undersampled radial CAIPI data.
PMID- 27502699
TI - Anticompulsive Activity of a New Pyrazolo[C]Pyridine Derivative GIZh-72 under
Conditions of Unpredictable Chronic Mild Stress.
AB - Anticompulsive activity of a novel compound GIZh-72 (4,6-dimethyl-2-(4
chlorphenyl)-2,3-dihydro-1H-pyrazolo[4,3-C]Pyridine-3-on, chloral hydrate) in a
dose of 20 mg/kg (single, subchronic, and chronic administration) in comparison
with fluvoxamine (25 mg/kg) was studied in the marble burying test in the model
of unpredictable chronic mild stress on BALB/c mice. GIZh-72 produced an
anticompulsive effect that increased with increasing treatment duration under
stress conditions in contrast to fluvoxamine that induced inversion of this
effect after long-term administration. Neuroleptic activity of GIZh-72 in doses
of 20 and 40 mg/kg was studied on the model of apomorphine-induced climbing in
C57Bl/6 mice. In contrast to haloperidol (0.5 mg/kg), GIZh-72 exhibited no
neuroleptic properties. Our results indicate that GIZh-72 holds much promise for
pharmacotherapy of obsessive-compulsive disorder.
PMID- 27502700
TI - Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for
Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary
Arterial Hypertension.
AB - A series of potent PDGFR inhibitors has been identified. The series was optimized
for duration of action in the lung. A novel kinase occupancy assay was used to
directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h
occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy
at 0.03 mg/kg, in the rat moncrotaline model of pulmonary arterial hypertension.
Examination of PK/PD data from the optimization effort has revealed in vitro:in
vivo correlations which link duration of action in vivo with low permeability and
high basicity and demonstrate that nonspecific binding to lung tissue increases
with lipophilicity.
PMID- 27502702
TI - Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human
colorectal cancer.
AB - BACKGROUND: Circulating microRNAs (miRNAs) are attracting major interest as
potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed
to identify a novel serum miRNA biomarker for the early detection and/or
evaluating prognosis of CRC patients. PATIENTS AND METHODS: Comprehensive miRNA
array analysis was carried out using serum samples from patients with colorectal
neoplasia and healthy controls. Next, to verify whether the candidate miRNA
possessed a secretory potential, we screened miRNA expression levels in culture
medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12
adenoma, and 12 control subjects. Thereafter, we validated expression of
candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an
independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. RESULTS:
Through microarray analysis, we identified significantly higher levels of miRNA
1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We
verified miR-1290 overexpression in serum of CRC patients in a training cohort.
In the validation cohort, serum miR-1290 levels were significantly up-regulated
in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum
miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) =
0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290
expression in serum and tissue was significantly associated with tumor
aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an
independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval
(CI) = 1.23-23.69; P = 0.0096] and an independent predictor for tumor recurrence
(hazard ratio = 3.92; 95% confidence interval = 1.11-25.14; P = 0.032) in CRC.
CONCLUSIONS: Serum miR-1290 is a novel biomarker for early detection, recurrence,
and prognosis in CRC.
PMID- 27502701
TI - Selection of an early biomarker for vascular normalization using dynamic contrast
enhanced ultrasonography to predict outcomes of metastatic patients treated with
bevacizumab.
AB - BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for
evaluation of tumor response to antiangiogenic treatments. The objective of this
study was to assess the link between DCE-US data obtained during the first week
of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients
treated with antiangiogenic therapies were included in a multicentric prospective
study from 2007 to 2010. DCE-US examinations were available at baseline and at
day 7. For each examination, a 3 min perfusion curve was recorded just after
injection of a contrast agent. Each perfusion curve was modeled with seven
parameters. We analyzed the correlation between criteria measured up to day 7 on
freedom from progression (FFP). The impact was assessed globally, according to
tumor localization and to type of treatment. RESULTS: The median follow-up was 20
months. The mean transit time (MTT) evaluated at day 7 was the only criterion
significantly associated with FFP (P = 0.002). The cut-off point maximizing the
difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a
better FFP. The results according to tumor type were significantly heterogeneous:
the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for
colon cancer (P = 0.025) than for other tumor types. Similarly, the differences
in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving
bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly
correlated to FFP of patients treated with bevacizumab. This criterion might be
linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.
PMID- 27502703
TI - Improved survival with dose-escalated radiotherapy in stage III non-small-cell
lung cancer: analysis of the National Cancer Database.
AB - BACKGROUND: Concurrent chemoradiation is the standard of care in non-operable
stage III non-small-cell lung cancer (NSCLC). Data have suggested a benefit of
dose escalation; however, results from the randomized dose-escalation trial RTOG
0617 revealed a lower survival rate with high-dose radiation. To evaluate the
impact of dose escalation on overall survival (OS) in stage III NSCLC treated
with chemoradiotherapy outside the controlled setting of a randomized trial, we
carried out an observational, population-based investigation of the National
Cancer Database (NCDB). PATIENTS AND METHODS: A total of 33 566 patients with
stage III NSCLC treated with chemoradiation from 2004 to 2012 and radiation doses
between 59.4 and 85 Gy were included. The primary end point was OS, with median
survival calculated via Kaplan-Meier. Univariate, multivariable and propensity
score matching analyses were carried out. RESULTS: Patients were stratified by
dose with median OS of: 18.8, 19.8 and 21.6 months for cohorts receiving 59.4-60,
61-69 and >=70 Gy, respectively (P < 0.001). Granular dose analyses were carried
out demonstrating increased OS with increasing radiation dose: median survival of
18.8, 21.1, 22.0 and 21.0 months for 59.4-60, 66, 70 and >=71 Gy, respectively.
While 66, 70 and >=71 Gy resulted in increased OS in comparison with 59.4-60 Gy,
no significant difference in OS was observed when comparing 66 with >=71 Gy (P =
0.38). CONCLUSIONS: Dose escalation above 60 Gy was associated with improved OS
in this cohort of stage III NSCLC patients treated with chemoradiotherapy. A
plateau of benefit was observed, with no additional improvement in OS with
increased dose (>=71 Gy) compared with 66-70 Gy. With evidence suggesting worse
OS and quality of life with increased dose, these data support investigation of
the role of intermediate-dose radiation, and in the absence of randomized
evidence, may be leveraged to justify utilization of intermediate-dose radiation.
PMID- 27502704
TI - Distinct subclonal tumour responses to therapy revealed by circulating cell-free
DNA.
AB - BACKGROUND: The application of precision medicine in oncology requires in-depth
characterisation of a patient's tumours and the dynamics of their responses to
treatment. PATIENTS AND METHODS: We used next-generation sequencing of
circulating cell-free DNA (cfDNA) to monitor the response of a KIT p.L576P-mutant
metastatic vaginal mucosal melanoma to sequential targeted, immuno- and
chemotherapy. RESULTS: Despite a KIT mutation, the response to imatinib was
mixed. Unfortunately, tumours were not accessible for molecular analysis. To
study the mechanism underlying the mixed clinical response, we carried out whole
exome sequencing and targeted longitudinal analysis of cfDNA. This revealed two
tumour subclones; one with a KIT mutation that responded to imatinib and a second
KIT-wild-type subclone that did not respond to imatinib. Notably, the subclones
also responded differently to immunotherapy. However, both subclones responded to
carboplatin/paclitaxel, and although the KIT-wild-type subclone progressed after
chemotherapy, it responded to subsequent re-administration of paclitaxel.
CONCLUSION: We show that cfDNA can reveal tumour evolution and subclonal
responses to therapy even when biopsies are not available.
PMID- 27502705
TI - Establishing a complementary diagnostic for anti-PD-1 immune checkpoint inhibitor
therapy.
PMID- 27502706
TI - The clinical dilemma of grade 3 follicular lymphoma.
PMID- 27502707
TI - Is the Gleason score the driver for the treatment decision-making of patients
with castration-resistant prostate cancer in the new era of the anti-androgenic
therapies?
PMID- 27502708
TI - Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.
AB - BACKGROUND: Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The
inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro
proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral
adenosine triphosphate-competitive AURKA inhibitor. PATIENTS AND METHODS: This
Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was
conducted through the Alliance for Clinical Trials in Oncology (A091102).
Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii)
leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve
sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every
21 days. The primary end point was response rate; progression-free survival (PFS)
was secondary. One response in the first 9 patients expanded enrollment in a
cohort to 24 using a Simon two-stage design. RESULTS: Seventy-two patients were
enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath
tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4%
were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other
sarcoma cohort. The histology-specific cohorts ceased at the first stage. There
were two confirmed PRs in the other cohort (both angiosarcoma) and one
unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS),
44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral
mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%),
and neutropenia (42%). CONCLUSIONS: Alisertib was well tolerated. Occasional
responses, yet prolonged stable disease, were observed. Although failing to meet
the primary RR end point, PFS was promising. TRIAL REGISTRATION ID: NCT01653028.
PMID- 27502709
TI - Temporal and spatial discordance of programmed cell death-ligand 1 expression and
lymphocyte tumor infiltration between paired primary lesions and brain metastases
in lung cancer.
AB - BACKGROUND: The dynamics of PD-L1 expression may limit its use as a tissue-based
predictive biomarker. We sought to expand our understanding of the dynamics of PD
L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung
cancer-related brain metastases. EXPERIMENTAL DESIGN: Paired primary lung cancers
and brain metastases were identified and assessed for PD-L1 and CD3 expression by
immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered
positive. Agreement statistics and the chi(2) or Fisher's exact test were used
for analysis. RESULTS: We analyzed 146 paired lesions from 73 cases. There was
disagreement of tumor cell PD-L1 expression in 10 cases (14%, kappa = 0.71), and
disagreement of TIL PD-L1 expression in 19 cases (26%, kappa = 0.38). Most paired
lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more
months apart. When specimens were categorized using a proposed tumor
microenvironment categorization scheme based on PD-L1 expression and TILs, there
were significant changes in the classifications because many of the brain
metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both
even when they were present in the primary lung cancer specimens (P = 0.009).
CONCLUSIONS: We identified that there are significant differences between the
tumor microenvironment of paired primary lung cancers and brain metastases. When
physicians decide to treat patients with lung cancer with a PD-1 or PD-L1
inhibitor, they must do so in the context of the spatial and temporal
heterogeneity of the tumor microenvironment.
PMID- 27502710
TI - Open-label, randomized study of individualized, pharmacokinetically (PK)-guided
dosing of paclitaxel combined with carboplatin or cisplatin in patients with
advanced non-small-cell lung cancer (NSCLC).
AB - BACKGROUND: Variable chemotherapy exposure may cause toxicity or lack of
efficacy. This study was initiated to validate pharmacokinetically (PK)-guided
paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to
avoid supra- or subtherapeutic exposure. PATIENTS AND METHODS: Patients with
newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles
of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard
paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In
arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and
subsequent doses were guided by neutropenia and previous-cycle paclitaxel
exposure [time above a plasma concentration of 0.05 uM (Tc>0.05)] determined from
a single blood sample on day 2. The primary end point was grade 4 neutropenia;
secondary end points included neuropathy, radiological response, progression-free
survival (PFS) and overall survival (OS). RESULTS: Among 365 patients randomly
assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P =
0.10). Neuropathy grade >=2 (38% versus 23%, P < 0.001) and grade >=3 (9% versus
2%, P < 0.001) was significantly lower in arm B, independent of the platinum drug
used. The median final paclitaxel dose was significantly lower in arm B (199
versus 150 mg/m(2), P < 0.001). Response rate was similar in arms A and B (31%
versus 27%, P = 0.405), as was adjusted median PFS [5.5 versus 4.9 months, hazard
ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.49, P = 0.228] and OS (10.1
versus 9.5 months, HR 1.05, 95% CI 0.81-1.37, P = 0.682). CONCLUSION: PK-guided
dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel
associated neuropathy and thereby improves the benefit-risk profile in patients
with advanced NSCLC. CLINICAL TRIAL INFORMATION: NCT01326767
(https://clinicaltrials.gov/ct2/show/NCT01326767).
PMID- 27502711
TI - Statistical controversies in clinical research: should schedules of tumor size
assessments be changed?
AB - BACKGROUND: Time to progression (TTP) is often used as a primary end point in
phase II clinical trials. Since the actual date of nadir and progression is never
known, most calculated TTP are overestimated. This study evaluates the
imprecision on the estimate of TTP under two hypothetical tumor kinetic settings
and various assessment schedules. DESIGN: A two-component tumor growth model was
used to account for treatment effect assuming exponential decay for tumor
shrinkage and linear growth for progression. Evolution of tumor burden (TB) was
modelized according to two scenarios using either a cytotoxic or a cytostatic
agent and several assessment schedules. TB, nadir, progression and TTP were
simulated for each visit schedule. RESULTS: For cytotoxic agents, our model
predicted response at 1.5 weeks, a TB at nadir of 40.2 mm (starting from 100 mm)
occurring at 6.7 weeks and true progression at 11.2 weeks with a TB of 48.2 mm.
For cytostatic agents, our model predicted no response, a TB at nadir of 77 mm
occurring at 9.2 weeks and true progression at 19.4 weeks with a TB of 92 mm.
Depending on the assessment schedule, estimated TTP was increased from 0.8 to
36.8 weeks and from 0.6 to 28.6 weeks when compared with the true TTP and varied
from 5.2% to 298% and from 1.66 to 109.58% when compared with the true TB at
progression for cytotoxic and cytostatic agents, respectively. Our model further
shows that for cytotoxic agents, evaluation of TB every 6 weeks is optimal to
capture the true nadir, the time to nadir, the true progression and the true TTP,
whereas for cytostatic agents, this evaluation is optimal every 10 weeks.
CONCLUSIONS: Our results emphasize the importance to estimate the effects of
tested drugs on tumor shrinkage before design any phase II clinical trials to
choose optimal TB evaluation's timing.
PMID- 27502713
TI - Reply to the letter to the editor 'Epstein-Barr virus reactivation in extranodal
natural killer/T-cell lymphoma patients: a previously unrecognized serious
adverse event in a pilot study with romidepsin, histone deacetylase (HDAC)
inhibitors when combined with a proteasome inhibitor are safe and effective in
patients with extranodal natural killer/T-cell lymphoma' by Tan et al.
PMID- 27502712
TI - Prospective assessment of a gene signature potentially predictive of clinical
benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic
(PREDICT).
AB - BACKGROUND: Genomic profiling of tumor tissue may aid in identifying predictive
or prognostic gene signatures (GS) in some cancers. Retrospective gene expression
profiling of melanoma and non-small-cell lung cancer led to the characterization
of a GS associated with clinical benefit, including improved overall survival
(OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the
present study was to prospectively evaluate the predictive value of the
previously characterized GS. PATIENTS AND METHODS: An open-label prospective
phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage
IIIB-C/IV-M1a melanoma. RESULTS: Of 123 subjects who received the MAGE-A3
immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS
rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free
survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to
treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response
(GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was
similarly immunogenic in both populations and had a clinically acceptable safety
profile. CONCLUSION: Treatment of patients with MAGE-A3-positive unresectable
stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an
overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS
rates, indicating that in this study, GS was not predictive of outcome.
Unexpectedly, the objective response rate was lower in this study than in other
studies carried out in the same setting with the MAGE-A3 immunotherapeutic.
Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3
immunotherapeutic treatment is ongoing in another melanoma study.This study is
registered at www.clinicatrials.gov NCT00942162.
PMID- 27502714
TI - Tolerability of immune checkpoint inhibition cancer therapy in a cardiac
transplant patient.
PMID- 27502715
TI - Sustained response to salvage therapy for dabrafenib-resistant metastatic
Langerhans cell sarcoma.
PMID- 27502716
TI - The obese endometrial cancer patient: how do we effectively improve morbidity and
mortality in this patient population?
AB - The relationship between obesity, metabolic syndrome, and endometrial cancer has
been established and accepted for decades. However, despite this understanding,
endometrial cancer patients continue to die of their obesity-related
comorbidities such as cardiovascular disease and diabetes. Furthermore, studies
show that gynecologic oncologists, general obstetrician/gynecologists, and
bariatric specialists do not appropriately address obesity as a risk factor for
cancer and also do not provide appropriate counseling on weight loss and
lifestyle modification during screening, diagnosis, and follow-up for endometrial
cancer. Given the increasing numbers of obese women both in the United States as
well as globally, it is imperative that this risk be addressed and mitigated
during patient interactions. Therefore, this article reviews the literature on
obesity, metabolic syndrome, and endometrial cancer, as well as the literature on
causes of death in endometrial cancer patients. Given the increased
cardiovascular and all-cause mortality, we provide a number of methods to address
obesity as a risk factor for cancer during patient visits. These methods include
self-directed diet and exercise, supervised diet and exercise programs, medical
management with insulin-sensitizing agents and statins, as well as bariatric
surgery in extreme cases. Furthermore, we also encourage collaboration between
general obstetrician/gynecologists, gynecologic oncologists, and bariatric
specialists in the care of obese endometrial cancer patients to ensure that they
not only survive their diagnosis, but also go on to live long, healthy lives.
PMID- 27502717
TI - Tumor-related leukocytosis is associated with poor radiation response and
clinical outcome in uterine cervical cancer patients.
AB - BACKGROUND: To evaluate response to radiation and clinical outcome of uterine
cervical cancer patients with tumor-related leukocytosis (TRL) at initial
diagnosis and during definitive radiotherapy. PATIENTS AND METHODS: We
retrospectively analyzed 2456 patients with stage IA-IVA uterine cervical cancer
who received definitive radiotherapy with (37.4%) or without (62.6%) platinum
based chemotherapy between 1986 and 2012. TRL was defined as two or more
occurrences of leukocytosis over 9000/MUl at the time of diagnosis and during the
course of treatment. Locoregional failure-free survival (LFFS) and overall
survival (OS) were compared between patients with or without TRL. RESULTS: The
median age of all patients was 55 years, and the median follow-up time was 65.1
months. TRL was observed in 398 patients (16%) at initial diagnosis; TRL (+)
patients were younger and had larger tumors, advanced stage, and more frequent
lymph node metastases (all P < 0.05). TRL (+) patients showed a significantly
lower rate of complete remission than TRL (-) patients (89.9% versus 96.3%,
respectively, P = 0.042). Ten-year LFFS and OS for all patients were 84% and 78%,
respectively. LFFS and OS were significantly lower in TRL (+) patients than TRL (
) patients (10-year LFFS: 69% versus 87% respectively, P < 0.001; 10-year OS: 63%
versus 81% respectively P < 0.001). After propensity score matching, LFFS and OS
rates in TRL (+) patients remained significantly lower than for TRL (-) patients;
this significant difference was also observed on multivariate analysis. Twenty
six percent of patients with locoregional failure (n = 345) were TRL (+) and had
significantly poorer median OS (6 versus 12 months, P = 0.001). CONCLUSION: This
study reveals the aggressive nature of cervical cancer with TRL and its poor
response to radiation therapy. Given the unfavorable prognosis and higher
probability of treatment failure, optimal diagnostic and therapeutic approaches
and careful monitoring for early detection of recurrence should be considered for
these patients.
PMID- 27502718
TI - Utilisation of the ESMO-MCBS in practice of HTA.
PMID- 27502719
TI - Possible determinants of VSL#3 probiotic failure in preventing gastrointestinal
adverse events associated with dacomitinib in patients with advanced non-small
cell lung cancer enrolled in ARCHER-1042 trial.
PMID- 27502720
TI - Reply to the letter to the editor 'the clinical dilemma of grade 3 follicular
lymphoma' by Sorigue et al.
PMID- 27502721
TI - Higher rate of severe toxicities in obese patients receiving dose-dense (dd)
chemotherapy according to unadjusted body surface area: results of the
prospectively randomized GAIN study.
AB - BACKGROUND: In routine clinical practice, chemotherapy doses are frequently
capped at a body surface area (BSA) of 2.0 m2 or adjusted to an ideal weight for
obese patients due to safety reasons. MATERIALS AND METHODS: Between August 2004
and July 2008, a total of 3023 patients were enrolled in the GAIN study, a
randomized phase III adjuvant trial, comparing two types of dose-dense (dd)
regimen [epirubicin, docetaxel and cyclophosphamide (iddETC) versus epirubicin
and cyclophosphamide (EC) followed by docetaxel (T) plus capecitabine (X)]. We
retrospectively evaluated a total of 555 patients with a BMI of >=30 for safety
and outcome. RESULTS: Eighteen percent of all patients were obese: 31% of those
received chemotherapy according to an unadjusted BSA. For the remaining patients,
BSA was adjusted to ideal weight or was capped at 2.0 m2. A total of 15% of obese
patients receiving full (unadjusted) dose of chemotherapy versus 6% of obese
patients with an adjusted BSA experienced febrile neutropenia (P = 0.003) and 9%
versus 3% high-grade thrombopenia (P = 0.002). Overall, 17% versus 10% had a
thromboembolic event (P = 0.017), which was high grade in 13% versus 6%,
respectively (P = 0.019), and 3% versus 0.3% high-grade hot flushes (P = 0.013).
Dizziness (5% versus 11%; P = 0.016), diarrhea (19% versus 27%; P = 0.033) and an
increase in serum creatinine (7% versus 14%; P = 0.019) were higher in the
adjusted group. However, no differences in disease-free survival (DFS) and
overall survival (OS) were observed between non-obese patients, obese patients
receiving full-dose chemotherapy or according to an adjusted BSA [5-year DFS 81%
(confidence interval 79% to 83%) versus 82% (75% to 87%) versus 81% (76% to 84%);
P = 0.761; 5-year OS 90% (88% to 91%) versus 86% (80% to 91%) versus 88% (84% to
91%); P = 0.143]. CONCLUSION: Obese patients receiving dd chemotherapy according
to their real BSA have a higher risk of developing severe toxicities without
influencing survival. Therefore, a dose adjustment of intense dd chemotherapy
should be carried out to avoid life-threatening complications.
PMID- 27502722
TI - Toward the molecular dissection of peritoneal pseudomyxoma.
AB - BACKGROUND: Outcome of pseudomyxoma peritonei (PMP) after cytoreductive surgery
(CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) is heterogeneous even
after adjusting for clinico-pathological prognostic variables. The identification
of additional prognostic or even predictive biomarkers is an unmet clinical need.
PATIENTS AND METHODS: Forty patients with mucinous appendiceal tumors and PMP
were clinically eligible and had evaluable tumor samples obtained after CRS and
HIPEC. We carried out next-generations sequencing (NGS) of 50 gene's hotspot
regions contained in the Hotspot Cancer Panel v2 using the Ion Torrent Personal
Genome Machine platform (Life Technologies). RESULTS: KRAS and GNAS mutations
were found in 72% and 52%, and their allelic frequency was below 10% in 55% and
43% of samples, respectively. KRAS and GNAS mutations were associated with worse
progression-free survival (PFS) at univariate analysis (P = 0.006 and 0.011,
respectively). At multivariate analysis, only KRAS mutations were independently
associated with PFS (P = 0.012); GNAS mutations were not-being significantly
associated with other poor prognostic features such as incomplete cytoreduction
or KRAS mutations. Validation of results was carried out in an independent bi
institutional cohort of 25 patients and the prognostic effect of KRAS mutations
was again confirmed in the multivariate model (P = 0.029). NGS approach allowed
the discovery of other potentially druggable mutations such as those in PI3K,
AKT, LKB1, FGFR3 and PDGFRA. CONCLUSIONS: Given the homogeneity of this series
and the sensitivity of NGS in this low-cellularity tumor, we demonstrated for the
first time a poor prognostic role of KRAS mutations.
PMID- 27502723
TI - Fertility-sparing surgery in epithelial ovarian cancer: a systematic review of
oncological issues.
AB - Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in
early-stage epithelial ovarian cancer (EOC) has been explored by several teams
and is reconsidered in this systematic review undertaken using the PRISMA
guidelines. Borderline ovarian tumours and non-EOCs were excluded. This review
comprises 1150 patients and 139 relapsing patients reported by 21 teams. This
conservative treatment can be safely carried out for stage IA and IC grade 1 and
2 disease and stage IC1 according to the new FIGO staging system. Nevertheless,
the number of patients reported with grade 2 disease is too small to definitively
confirm whether FSS is safe in this subgroup. For patients with 'less favourable'
prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be
confirmed, but patients should be informed that radical treatment probably may
not necessarily improve their oncological outcome, because the poorest survival
observed could be related to the natural history of the disease itself and not
specifically to the use of conservative therapy. FSS could probably be considered
in stage I clear-cell tumours but should remain contraindicated for stage II/III
disease (whatever the histologic subtype). As the disease stage and the
histologic data (tumour type and grade) are crucial to patient selection for this
treatment, this implies careful and mandatory complete surgical staging surgery
in this context and a pathological analysis (or review) of the tumour by an
expert pathologist.
PMID- 27502724
TI - Long-term outcomes of accelerated BEP (bleomycin, etoposide, cisplatin) for
advanced germ cell tumours: updated analysis of an Australian multicentre phase
II trial by the Australian and New Zealand Urogenital and Prostate Cancer Trials
Group (ANZUP).
PMID- 27502726
TI - Predictors of chemotherapy efficacy in non-small-cell lung cancer: a challenging
landscape.
AB - BACKGROUND: Conventional cytotoxic chemotherapy (CCC) is the backbone of non
small-cell lung cancer (NSCLC) treatment since decades and still represents a key
element of the therapeutic armamentarium. Contrary to molecularly targeted
therapies and immune therapies, for which predictive biomarkers of activity have
been actively looked for and developed in parallel to the drug development
process ('companion biomarkers'), no patient selection biomarker is currently
available for CCC, precluding customizing treatment. MATERIALS AND METHODS: We
reviewed preclinical and clinical studies that assessed potential predictive
biomarkers of CCC used in NSCLC (platinum, antimetabolites, topoisomerase
inhibitors, and spindle poisons). Biomarker evaluation method, analytical
validity, and robustness are described and challenged for each biomarker.
RESULTS: The best-validated predictive biomarkers for efficacy are currently
ERCC1, RRM1, and TS for platinum agents, gemcitabine and pemetrexed,
respectively. Other potential biomarkers include hENT1 for gemcitabine, class III
beta-tubulin for spindle poisons, TOP2A expression and CEP17 duplication (mostly
studied for predicting anthracyclines efficacy) whose applicability concerning
etoposide would deserve further evaluation. However, none of these biomarkers has
till now been validated prospectively in an appropriately designed and powered
randomised trial, and none of them is currently ready for implementation in
routine clinical practice. CONCLUSION: The search for predictive biomarkers to
CCC has been proven challenging. If a plethora of biomarkers have been evaluated
either in the preclinical or in the clinical setting, none of them is ready for
clinical implementation yet. Considering that most mechanisms of resistance or
sensitivity to CCC are multifactorial, a combinatorial approach might be relevant
and further efforts are required.
PMID- 27502725
TI - Final results of the TANIA randomised phase III trial of bevacizumab after
progression on first-line bevacizumab therapy for HER2-negative locally
recurrent/metastatic breast cancer.
AB - BACKGROUND: The randomised phase III TANIA trial demonstrated that continuing
bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast
cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy
significantly improved progression-free survival (PFS) compared with chemotherapy
alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61-0.93]. We
report final results from the TANIA trial, including overall survival (OS) and
health-related quality of life (HRQoL). PATIENTS AND METHODS: Patients with HER2
negative LR/mBC that had progressed on or after first-line bevacizumab plus
chemotherapy were randomised to receive standard second-line chemotherapy either
alone or with bevacizumab. At second progression, patients initially randomised
to bevacizumab continued bevacizumab with their third-line chemotherapy, but
those randomised to chemotherapy alone were not allowed to cross over to receive
third-line bevacizumab. The primary end point was second-line PFS; secondary end
points included third-line PFS, combined second- and third-line PFS, OS, HRQoL
and safety. RESULTS: Of the 494 patients randomised, 483 received second-line
therapy; 234 patients (47% of the randomised population) continued to third-line
study treatment. The median duration of follow-up at the final analysis was 32.1
months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus
chemotherapy arm. There was no statistically significant difference between
treatment arms in third-line PFS (HR = 0.79, 95% CI 0.59-1.06), combined second-
and third-line PFS (HR = 0.85, 95% CI 0.68-1.05) or OS (HR = 0.96, 95% CI 0.76
1.21). Third-line safety results showed increased incidences of proteinuria and
hypertension with bevacizumab, consistent with safety results for the second-line
treatment phase. No differences in HRQoL were detected. CONCLUSIONS: In this
trial, continuing bevacizumab beyond first and second progression of LR/mBC
improved second-line PFS, but no improvement in longer term efficacy was
observed. The second-line PFS benefit appears to be achieved without
detrimentally affecting quality of life. CLINICALTRIALSGOV: NCT01250379.
PMID- 27502727
TI - Searching for aurora in the night of sarcoma phase II trials: isn't it time to
move to second gear?
PMID- 27502728
TI - Prognostic value of tumor-infiltrating lymphocytes differs depending on
histological type and smoking habit in completely resected non-small-cell lung
cancer.
AB - BACKGROUND: T-cell infiltration in tumors has been used as a prognostic tool in
non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and
histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains
unclear. PATIENTS AND METHODS: We evaluated the prognostic significance of TILs
(CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit
using automatic immunohistochemical staining and cell counting in 218 patients
with NSCLC. RESULTS: In multivariate survival analyses of clinical, pathological,
and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4)
[hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05
for recurrence-free survival (RFS)] and a low accumulation of CD20+ B cells (HR:
2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse
prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number
of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01
for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high
FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01
for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells
(HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an
unfavorable factor in non-smokers with AD. CONCLUSIONS: A low number of CD8+ T
cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of
CD20+ B cells in non-smokers with AD were identified as independent unfavorable
prognostic factors in resected NSCLC. Evaluating the influence of histological
type and smoking habit on the immunological environment may lead to the
establishment of immunological diagnosis and appropriate individualized
immunotherapy for NSCLC.
PMID- 27502729
TI - Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as
adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive
early breast cancer: a multicenter randomized study by the Hellenic Oncology
Research Group (HORG).
AB - BACKGROUND: Sequential administration of anthracycline and taxane is the current
standard of care adjuvant regimen for node-positive early breast cancer. Due to
long-term toxicity concerns, anthracycline-free regimens have been developed. We
compared a sequential dose-dense anthracycline and taxane regimen with the
anthracycline-free regimen of docetaxel and cyclophosphamide. PATIENTS AND
METHODS: In this randomized, non-inferiority, phase III trial, women with HER2
negative invasive breast cancer and at least one positive axillary lymph node
were randomized to receive either epirubicin (75 mg/m(2)), 5-fluorouracil (500
mg/m(2)) and cyclophosphamide (500 mg/m(2)) every 2 weeks for four cycles,
followed by four cycles of docetaxel (75 mg/m(2)) every 2 weeks with prophylactic
G-CSF support (FEC -> D) or docetaxel (75 mg/m(2)) and cyclophosphamide (600
mg/m(2)) every 21 days for six cycles (TC). The primary end point of the study
was the 3-year disease-free survival (DFS) rate. RESULTS: Six hundred and fifty
women were randomized to either FEC -> D (n = 326) or TC (n = 324). After a
median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for
the FEC -> D and TC arm, respectively (hazard ratio = 1.147, 95% confidence
interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm
(32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low
(<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more
common with FEC -> D. Acute cardiotoxicity was rare (1 event in each group).
There were no toxic deaths. CONCLUSIONS: This trial did not clearly demonstrate
that TC is non-inferior to dose-dense FEC -> D. However, 3-year DFS rates were
excellent in both arms for women with node-positive, HER2-negative early breast
cancer. CLINICALTRIALSGOV: NCT01985724.
PMID- 27502730
TI - High power laser-driven ceramic phosphor plate for outstanding efficient white
light conversion in application of automotive lighting.
AB - We report on Y3Al5O12: Ce(3+) ceramic phosphor plate (CPP) using nano phosphor
for high power laser diode (LD) application for white light in automotive
lighting. The prepared CPP shows improved luminous properties as a function of
Ce(3+) concentration. The luminous properties of the Y3Al5O12: Ce(3+) CPP nano
phosphor are improved when compared to the Y3Al5O12: Ce(3+) CPP with bulk
phosphor, and hence, the luminous emittance, luminous flux, and conversion
efficiency are improved. The Y3Al5O12: Ce(3+) CPP with an optimal Ce(3+) content
of 0.5 mol % shows 2733 lm/mm(2) value under high power blue radiant flux density
of 19.1 W/mm(2). The results indicate that Y3Al5O12: Ce(3+) CPP using nano
phosphor can serve as a potential material for solid-state laser lighting in
automotive applications.
PMID- 27502731
TI - Water vapor delta(2) H, delta(18) O and delta(17) O measurements using an off
axis integrated cavity output spectrometer - sensitivity to water vapor
concentration, delta value and averaging-time.
AB - RATIONALE: High-precision analysis of atmospheric water vapor isotope
compositions, especially delta(17) O values, can be used to improve our
understanding of multiple hydrological and meteorological processes (e.g.,
differentiate equilibrium or kinetic fractionation). This study focused on
assessing, for the first time, how the accuracy and precision of vapor delta(17)
O laser spectroscopy measurements depend on vapor concentration, delta range, and
averaging-time. METHODS: A Triple Water Vapor Isotope Analyzer (T-WVIA) was used
to evaluate the accuracy and precision of delta(2) H, delta(18) O and delta(17) O
measurements. The sensitivity of accuracy and precision to water vapor
concentration was evaluated using two international standards (GISP and SLAP2).
The sensitivity of precision to delta value was evaluated using four working
standards spanning a large delta range. The sensitivity of precision to averaging
time was assessed by measuring one standard continuously for 24 hours. RESULTS:
Overall, the accuracy and precision of the delta(2) H, delta(18) O and delta(17)
O measurements were high. Across all vapor concentrations, the accuracy of
delta(2) H, delta(18) O and delta(17) O observations ranged from 0.100/00 to
1.840/00, 0.080/00 to 0.860/00 and 0.060/00 to 0.620/00, respectively, and the
precision ranged from 0.0990/00 to 0.4300/00, 0.0090/00 to 0.0800/00 and
0.0220/00 to 0.0540/00, respectively. The accuracy and precision of all isotope
measurements were sensitive to concentration, with the higher accuracy and
precision generally observed under moderate vapor concentrations (i.e., 10000
15000 ppm) for all isotopes. The precision was also sensitive to the range of
delta values, although the effect was not as large compared with the sensitivity
to concentration. The precision was much less sensitive to averaging-time than
the concentration and delta range effects. CONCLUSIONS: The accuracy and
precision performance of the T-WVIA depend on concentration but depend less on
the delta value and averaging-time. The instrument can simultaneously and
continuously measure delta(2) H, delta(18) O and delta(17) O values in water
vapor, opening a new window to better understand ecological, hydrological and
meteorological processes. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27502732
TI - Novel Poly(3-hydroxybutyrate-g-vinyl alcohol) Polyurethane Scaffold for Tissue
Engineering.
AB - The design of new synthetic grafted poly(3-hydroxybutyrate) as composite 3D
scaffolds is a convenient alternative for tissue engineering applications. The
chemically modified poly(3-hydroxybutyrate) is receiving increasing attention for
use as biomimetic copolymers for cell growth. As of yet, these copolymers cannot
be used efficiently because of the lack of good mechanical properties. Here, we
address this challenge, preparing a composite-scaffold of grafted poly(3
hydroxybutyrate) polyurethane for the first time. However, it is unclear if the
composite structure and morphology can also offer a biological application. We
obtained the polyurethane by mixing a polyester hydroxylated resin with
polyisocyanate and the modified polyhydroxyalkanoates. The results show that the
poly(3-hydroxybutyrate) grafted with poly(vinyl alcohol) can be successfully used
as a chain extender to form a chemically-crosslinked thermosetting polymer.
Furthermore, we show a proposal for the mechanism of the polyurethane synthesis,
the analysis of its morphology and the ability of the scaffolds for growing
mammalian cells. We demonstrated that astrocytes isolated from mouse cerebellum,
and HEK293 can be cultured in the prepared material, and express efficiently
fluorescent proteins by adenoviral transduction. We also tested the metabolism of
Ca(2+) to obtain evidence of the biological activity.
PMID- 27502733
TI - Intestinal infection at onset of mycophenolic acid-associated chronic diarrhea in
kidney transplant recipients.
AB - BACKGROUND: Chronic diarrhea after kidney transplantation is often attributed to
mycophenolic acid (MPA) toxicity. We hypothesize that intestinal infections
contribute to the pathogenesis of chronic MPA-associated diarrhea. METHODS: In
this retrospective study, all patients (n = 726) receiving a kidney transplant
between 2000 and 2010 at the University Hospital Zurich were followed until July
2014 for occurrence of chronic diarrhea (>=4 weeks). Infectious triggers at
diarrhea onset were assessed by reviewing medical history, stool microbiology,
and histology of colon biopsies. RESULTS: In 46 patients (6.3% of the cohort), a
total of 51 episodes of chronic diarrhea during MPA treatment were documented.
The diarrhea episodes were often severe, as confirmed by significant weight loss.
The cumulative incidence of chronic diarrhea was uniformly distributed throughout
the post-transplant period, with 2.0%, 5.1%, and 9.6% at 1, 5, and 10 years,
respectively. Evidence was found for intestinal infection at diarrhea onset in 38
episodes (74.5%). Occurrence of diarrhea onset showed a seasonal distribution
with peaks in April and October/November. Specific antimicrobial treatment alone
was associated with a 19% resolution rate only, whereas combination with dose
reduction of MPA or switch from mycophenolate mofetil to enteric-coated
mycophenolate sodium resulted in a 22.7% and 76.5% resolution rate, respectively.
Change to an MPA-free regimen was associated with a 100% resolution rate.
CONCLUSION: These results provide first evidence for a contribution of intestinal
infections in chronic post-transplant diarrhea associated with MPA treatment.
PMID- 27502735
TI - Pd Nanoparticles Decorated N-Doped Graphene Quantum Dots@N-Doped Carbon Hollow
Nanospheres with High Electrochemical Sensing Performance in Cancer Detection.
AB - The development of carbon based hollow-structured nanospheres (HNSs) materials
has stimulated growing interest due to their controllable structure, high
specific surface area, large void space, enhanced mass transport, and good
biocompatibility. The incorporation of functional nanomaterials into their core
and/or shell opens new horizons in designing functionalized HNSs for a wider
spectrum of promising applications. In this work, we report a new type of
functionalized HNSs based on Pd nanoparticles (NPs) decorated double shell
structured N-doped graphene quantum dots (NGQDs)@N-doped carbon (NC) HNSs, with
ultrafine Pd NPs and "nanozyme" NGQDs as dual signal-amplifying nanoprobes, and
explore their promising application as a highly efficient electrocatalyst in
electrochemical sensing of a newly emerging biomarker, i.e., hydrogen peroxide
(H2O2), for cancer detection. Due to the synergistic effect of the robust and
conductive HNS supports and catalytically active Pd NPs and NGQD in facilitating
electron transfer, the NGQD@NC@Pd HNS hybrid material exhibits high
electrocatalytic activity toward the direct reduction of H2O2 and can promote the
electrochemical reduction reaction of H2O2 at a favorable potential of 0 V, which
effectively restrains the redox of most electroactive species in physiological
samples and eliminates interference signals. The resultant electrochemical H2O2
biosensor based hybrid HNSs materials demonstrates attractive performance,
including low detection limit down to nanomole level, short response time within
2 s, as well as high sensitivity, reproducibility, selectivity, and stability,
and have been used in real-time tracking of trace amounts of H2O2 secreted from
different living cancer cells in a normal state and treated with chemotherapy and
radiotherapy.
PMID- 27502736
TI - Identification of IL6 as a susceptibility gene for major depressive disorder.
AB - Our previous work implied that interleukin 6 (IL6) may be a biological marker for
major depressive disorder (MDD). In this study, we performed a comprehensive
genetic study to determine the association between the gene encoding IL6 (IL6)
and MDD in Han Chinese. There were 50 drug-naive MDD patients and 50 healthy
controls undergoing an mRNA expression study. A sample of 772 patients with MDD
and 759 healthy controls were used for genetic analysis. Next, we performed an
eQTL analysis to identify whether risk SNP(s) is associated with IL6 expression
in brain. Our results showed that patients with MDD have higher levels of IL6
than healthy controls (P = 0.008). The SNP rs1800797 has a significant
association with MDD (P = 0.01) in a dominant model. The eQTL analysis showed a
marginally significant association between the rs1800797 and IL6 expression in
the frontal cortex (P = 0.087). Our preliminary findings are suggestive of an
association between rs1800797 and the risk of MDD. Further investigations are
required to evaluate this association in larger samples to increase statistical
power, and to examine the correlation between rs1800797 and IL6 methylation
patterns.
PMID- 27502737
TI - Predictors of duration of abiraterone acetate in men with castration-resistant
prostate cancer.
AB - BACKGROUND: Androgen receptor signaling remains important in castration-resistant
prostate cancer (CRPC) as demonstrated by the efficacy of abiraterone acetate
(henceforth abiraterone) in phase III trials. Given that heterogeneous patient
responses are observed, we sought to identify clinical factors associated with
duration of abiraterone. METHODS: We retrospectively identified patients with
CRPC treated with abiraterone in our database. Patient characteristics and types
and duration of prostate cancer (PC) therapies were analyzed. These parameters
were analyzed with duration of abiraterone in univariate and multivariable
analyses. RESULTS: We identified 161 patients who had received abiraterone. All
had received primary androgen-deprivation therapy (ADT), 86% prior secondary
hormone therapy (SHT) and 33% prior chemotherapy. The median duration of primary
ADT was 23 months, duration of SHT (excluding abiraterone) was 17 months and
duration of chemotherapy was 8 months. We demonstrated that lower PSA at
abiraterone initiation, longer primary ADT duration, no prior ketoconazole, no
prior chemotherapy and longer chemotherapy duration were associated with a longer
duration on abiraterone in univariate analysis. In multivariable analysis,
duration of primary ADT (duration of abiraterone 9 versus 13 months for ?12
versus >12 months, P=0.03) and no use of prior chemotherapy (duration of
abiraterone 16 versus 7 months for no versus yes prior chemotherapy, P<0.01) were
associated with duration of abiraterone. CONCLUSIONS: Several clinical
parameters, including type and duration of prior therapy, are predictive of
responsiveness to abiraterone. These parameters are logical and correlate with
smaller disease burden or less exposure to PC therapies. This information can
help physicians counsel patients about the potential durability of efficacy of
abiraterone. Identifying predictive biomarkers that inform patient selection for
therapy is critical to optimizing treatment outcomes.
PMID- 27502738
TI - Morbidity and mortality after surgery for lower urinary tract symptoms: a study
of 95 577 cases from a nationwide German health insurance database.
AB - BACKGROUND: Little real-world data is available on the comparison of different
methods in surgery for lower urinary tract symptoms due to benign prostatic
obstruction in terms of complications. The objective was to evaluate the
proportions of TURP, open prostatectomy (OP) and laser-based surgical approaches
over time and to analyse the effect of approach on complication rates. METHODS:
Using data of the German local healthcare funds (Allgemeine Ortskrankenkassen
(AOK)), we identified 95 577 cases with a primary diagnosis of hyperplasia of
prostate who received TURP, laser vaporisation (LVP), laser enucleation (LEP) of
the prostate or OP between 2008 and 2013. Univariable logistic regression was
used to analyse proportions of surgical approach over time, and the effect of
surgical method on outcomes was analysed by means of multivariable logistic
regression. RESULTS: The proportion of TURP decreased from 83.4% in 2008 to 78.7%
in 2013 (P<0.001). Relative to TURP and adjusting for age, co-morbidities, AOK
hospital volume, year of surgery and antithrombotic medication, OP had increased
mortality (odds ratio (OR) 1.47, P<0.05), transfusions (OR 5.20, P<0.001) and
adverse events (OR 2.17, P<0.001), and lower re-interventions for bleeding (OR
0.75, P<0.001) and long-term re-interventions (OR 0.55, P<0.001). LVP carried a
lower risk of transfusions (OR 0.57, P<0.001) and re-interventions for bleeding
(OR 0.76, P<0.001), but a higher risk of long-term re-interventions (OR 1.43,
P<0.001). LEP had increased re-interventions for bleeding (OR 1.35, P<0.01).
Complications were also dependent on age and co-morbidity. Limitations include
the lack of clinical information and functional results. CONCLUSIONS: OP has the
greatest risks of complication despite a low re-intervention rate. LVP
demonstrated favourable results for transfusion and bleeding, but increased long
term re-interventions compared with TURP, while LEP showed increased re
interventions for bleeding. Findings support a careful indication and choice of
method for surgery for LUTS, taking age and co-morbidities into account.
PMID- 27502739
TI - Tumor features and survival after radical prostatectomy among antidiabetic drug
users.
AB - BACKGROUND: To evaluate the association between use of metformin and other
antidiabetic drugs with tumor characteristics and survival in surgically managed
prostate cancer (PCa) patients. METHODS: The study population included 1314 men
who underwent radical prostatectomy at the Tampere University Hospital during
1995-2009. Causes of deaths were collected from the Finnish Cancer Registry.
Individual-level data on medication use during 1995-2009 was obtained from
national prescription database. Fasting blood glucose and hemoglobin A1c values
during the study period were gathered from hospital district database. Gleason
grade and pathological stage were compared by drug use before surgery and
separately by metformin usage. Risk of biochemical recurrence, all-cause death
and PCa-specific death were calculated using Cox proportional hazard regression
with adjustment for age, tumor characteristics, glycemic control and use of other
drug groups. RESULTS: High-grade tumors were more common among antidiabetic drug
users (P=0.032), including metformin users (P=0.012). Despite this, no difference
in PSA levels was observed. Men who had used antidiabetic drugs before surgery
had an increased risk of Gleason 7-10 disease (odds ratio (OR) 1.83, 95%
confidence interval (CI) 1.04-3.23). The risk of high-grade PCa was higher among
metformin users compared with other antidiabetic drug users (OR 3.11, 95% CI 1.16
8.33). During the median follow-up of 8.6 years after surgery, 551 men had
biochemical recurrence and 244 died, 32 owing to PCa. Generally, no association
with risk of disease recurrence was observed. Risk of death was increased by
preoperative use of antidiabetic drugs (hazard ratio 1.81 95% CI 1.03-3.19), but
no survival associations for postoperative use of antidiabetic drugs or metformin
were observed. CONCLUSION: Diabetic men have more high-grade PCa at lower PSA
levels, but that does not have a clear impact on disease-specific survival in the
short term even when glycemic control is being considered.
PMID- 27502740
TI - The concordance between the volume hotspot and the grade hotspot: a 3-D
reconstructive model using the pathology outputs from the PROMIS trial.
PMID- 27502741
TI - The contribution of the citrate pathway to oxidative stress in Down syndrome.
AB - Inflammatory conditions and oxidative stress have a crucial role in Down syndrome
(DS). Emerging studies have also reported an altered lipid profile in the early
stages of DS. Our previous works demonstrate that citrate pathway activation is
required for oxygen radical production during inflammation. Here, we find up
regulation of the citrate pathway and down-regulation of carnitine/acylcarnitine
carrier and carnitine palmitoyl-transferase 1 genes in cells from children with
DS. Interestingly, when the citrate pathway is inhibited, we observe a reduction
in oxygen radicals as well as in lipid peroxidation levels. Our preliminary
findings provide evidence for a citrate pathway dysregulation, which could be
related to some phenotypic traits of people with DS.
PMID- 27502742
TI - A circuit motif in the zebrafish hindbrain for a two alternative behavioral
choice to turn left or right.
AB - Animals collect sensory information from the world and make adaptive choices
about how to respond to it. Here, we reveal a network motif in the brain for one
of the most fundamental behavioral choices made by bilaterally symmetric animals:
whether to respond to a sensory stimulus by moving to the left or to the right.
We define network connectivity in the hindbrain important for the lateralized
escape behavior of zebrafish and then test the role of neurons by using laser
ablations and behavioral studies. Key inhibitory neurons in the circuit lie in a
column of morphologically similar cells that is one of a series of such columns
that form a developmental and functional ground plan for building hindbrain
networks. Repetition within the columns of the network motif we defined may
therefore lie at the foundation of other lateralized behavioral choices.
PMID- 27502743
TI - Breslow density is a novel prognostic feature in cutaneous malignant melanoma.
AB - AIMS: In 1970, Breslow described his eponymously named thickness measurement. No
one has sought to enhance the Breslow thickness (BT). The aim of this study was
to demonstrate a proof of concept that the density of melanoma cells at the
position where the BT is measured is a morphological prognostic biomarker, which
we name the Breslow density (BD). The hypothesis was that the BD has prognostic
value for overall survival (OS) and is independent of the BT. METHODS AND
RESULTS: We analysed 100 cutaneous melanomas, and followed REMARK guidelines. The
BD was the estimated percentage dermal area occupied by melanoma cells in a
specified location. The BT and BD had a strong correlation (P = 2.1 * 10-11 )
but, despite this, they were independent prognostic factors for OS in Cox
regression [BD hazard ratio (HR) 1.03, P = 0.001849; and BT HR 1.09, P =
0.000146]. This was corroborated by an independent effect on melanoma-specific
survival. We assessed whether the BT and BD could be combined into a Breslow
score. A prognostic index based on Cox regression coefficients was used, and this
showed a marginal improvement in predicted 5-year survival as compared with the
BT alone (area under the curve of 94.8% versus 96.7%). CONCLUSIONS: We show a
proof of concept that the BD represents a novel morphological prognostic
biomarker that is independent of the BT, and that there is potential to combine
these into a Breslow score. Larger studies are needed to validate the BD, but the
simplicity of this biomarker makes it a strong candidate for translation to
clinical practice.
PMID- 27502744
TI - Real-world implementation of electronic patient-reported outcomes in outpatient
pediatric cancer care.
AB - OBJECTIVE: The KLIK method is an online tool that monitors and discusses
electronic patient-reported outcomes (ePROs), which has been shown to enhance
outcomes. This study aimed (1) to determine the fidelity (ie, extent to which
used as intended) of the KLIK method as implemented in outpatient pediatric
cancer care and (2) to study health care professional (HCP)-reported barriers and
facilitators for implementation. METHODS: Two hundred five children with newly
diagnosed cancer (enrollment rate 85%) participated. At 1 (T1), 3 (T2), and 6
(T3) months after diagnosis, patients (8-18 years) or parents (of patients 0-7
years) completed health-related quality of life (HRQoL) questionnaires, which
were transformed into an ePROfile and discussed by their HCP during
consultations. Fidelity was determined by the following: percentage of website
registrations, HRQoL questionnaires completed, and ePROfiles discussed.
Implementation determinants were assessed with HCPs after the final T3 with the
Measurement Instrument for Determinants of Innovations. RESULTS: Depending on the
time point (T1-T3), fidelity was 86% to 89% for website registration, 66-85% for
completed HRQoL questionnaires, and 56% to 62% for ePROfile discussion. Barriers
were mainly related to organizational issues (eg, organizational change) and less
frequently to users (eg, motivation to comply) or the intervention
(compatibility). Facilitators were related to the user (eg, positive outcome
expectations) and intervention (simplicity) but not to the organization.
CONCLUSIONS: When implementing ePROs in outpatient pediatric oncology practice,
HCPs report determinants that influence ePRO integration. To improve
implementation and outcomes, tailored organizational (eg, formal ratification by
management and time) and specific local (eg, individualized assessments)
strategies should be developed to achieve optimal ePRO discussion.
PMID- 27502745
TI - Promiscuous Pathogenicity Islands and Phylogeny of Pathogenic Streptomyces spp.
AB - Approximately 10 Streptomyces species cause disease on underground plant
structures. The most economically important of these is potato scab, and the most
studied of these pathogens is Streptomyces scabiei (syn. S. scabies). The main
pathogenicity determinant of scab-causing Streptomyces species is a nitrated
diketopiperazine, known as thaxtomin A (ThxA). In the pathogenic species
Streptomyces turgidiscabies, ThxA biosynthetic genes reside on a mobile
pathogenicity island (PAI). However, the mobilization of PAIs in other
Streptomyces species remains uncharacterized. Here, we investigated the
mobilization of the PAI of S. scabiei 87-22. Based on whole genome sequences, we
inferred the evolutionary relationships of pathogenic Streptomyces species and
discovered that Streptomyces sp. strain 96-12, a novel pathogenic species
isolated from potatoes in Egypt, was phylogenetically grouped with nonpathogenic
species rather than with known pathogenic species. We also found that
Streptomyces sp. strain 96-12 contains a PAI that is almost identical to the PAI
in S. scabiei 87-22, despite significant differences in their genome sequences.
This suggested direct or indirect in vivo mobilization of the PAI between S.
scabiei and nonpathogenic Streptomyces species. To test whether the S. scabiei 87
22 PAI could, indeed, be mobilized, S. scabiei 87-22 deletion mutants containing
antibiotic resistance markers in the PAI were mated with Streptomyces
diastatochromogenes, a nonpathogenic species. The PAI of S. scabiei was site
specifically inserted into the aviX1 gene of S. diastatochromogenes and conferred
pathogenicity in radish seedling assays. Our results demonstrated that S.
scabiei, the earliest described Streptomyces pathogen, could be the source of a
PAI responsible for the emergence of novel pathogenic species.
PMID- 27502746
TI - Concentrations of 226Ra, 232Th and 40K in industrial kaolinized granite.
AB - Activity concentrations of 226Ra, 232Th and 40K in 120 kaolinized granite samples
imported in Serbia from the Motajica mine, Bosnia and Herzegovina, were measured.
The 226Ra concentration ranged from 61 to 319 Bq kg-1, the 232Th from 44 to 272
Bq kg-1, and the 40K from 590 to 1470 Bq kg-1. The frequency distribution of 40K
concentrations was near-Gaussian, where those of 226Ra and 232Th were right
skewed. In 6 samples, the gamma index, I, was higher than 2, which exceeds the
exemption dose criterion (0.3 mSv y-1). The absorbed dose rate and annual
effective doses for workers in the ceramic industries in Serbia who worked with
kaolinized granite were below levels of concern.
PMID- 27502747
TI - 210Po and 210Pb disequilibrium at the PN section in the East China Sea.
AB - Lead-210 and 210Po have been widely used as tracers for quantifying particulate
scavenging in the upper layer of the oceanic water column. In this study, we
investigated the 210Po/210Pb disequilibrium in the water column of the PN section
in the East China Sea (ECS) during autumn 2013. In most of the water column, a
deficiency of 210Po was observed with respect to its parent nuclide 210Pb (i.e.,
a 210Po/210Pb activity ratio < 1.0). The (210Po/210Pb)dissolved,
(210Po/210Pb)particulate and (210Po/210Pb)total activity ratios ranged from 0.29
to 0.71 (average: 0.53 +/- 0.13, n = 27), 0.31 to 1.42 (average: 0.70 +/- 0.27, n
= 27) and 0.22 to 0.62 (average: 0.50 +/- 0.12, n = 27), respectively. The
distribution coefficients (Kd) of 210Po and 210Pb were 12.1* 104 ml g-1 and 8.8*
104 ml g-1, with an average (210Po/210Pb) total activity ratio of (0.50 +/- 0.12,
n = 27). However, over the continental shelf, planktonic detritus and fecal
pellets appear to be the main carriers for 210Po, which preferentially scavenges
210Po and produces a lower (210Po/210Pb) total activity ratio (0.49 +/- 0.12, n =
22) with a Kd for 210Po of 13.8* 104 ml g-1 in the water column. The variations
in the fractionation factor (1.48 +/- 0.66) of 210Po/210Pb reveal distinct
differences between the distribution and scavenging of 210Po and 210Pb by
particulate matter in different marine environments: in the estuarine zone (a
high turbidity area), terrigenous suspended particulate matter scavenges 210Pb
from the water column, while in areas dominated by biogenic particular matter,
210Po is preferentially scavenged from the water column. Using the 210Po/210Pb
disequilibrium in the water column, we estimated the removal fluxes of POC from
the upper waters downward to be 25.0 mg C m-2 d-1, comparable to those in other
marginal seas. Moreover, a decreasing trend of POC removal fluxes was observed
with increasing distance offshore.
PMID- 27502750
TI - The contributions of resting state and task-based functional connectivity studies
to our understanding of adolescent brain network maturation.
AB - This review summarizes functional magnetic resonance imaging (fMRI) research done
over the past decade that examined changes in the function and organization of
brain networks across human adolescence. Its over-arching goal is to highlight
how both resting state functional connectivity (rs-fcMRI) and task-based
functional connectivity (t-fcMRI) have jointly contributed - albeit in different
ways - to our understanding of the scope and types of network organization
changes that occur from puberty until young adulthood. These two approaches
generally have tested different types of hypotheses using different analysis
techniques. This has hampered the convergence of findings. Although much has been
learned about system-wide changes to adolescents' neural network organization, if
both rs-fcMRI and t-fcMRI approaches draw upon each other's methodology and ask
broader questions, it will produce a more detailed connectome-informed theory of
adolescent neurodevelopment to guide physiological, clinical, and other lines of
research.
PMID- 27502748
TI - Electronic approaches to restoration of sight.
AB - Retinal prostheses are a promising means for restoring sight to patients blinded
by the gradual atrophy of photoreceptors due to retinal degeneration. They are
designed to reintroduce information into the visual system by electrically
stimulating surviving neurons in the retina. This review outlines the concepts
and technologies behind two major approaches to retinal prosthetics: epiretinal
and subretinal. We describe how the visual system responds to electrical
stimulation. We highlight major differences between direct encoding of the
retinal output with epiretinal stimulation, and network-mediated response with
subretinal stimulation. We summarize results of pre-clinical evaluation of
prosthetic visual functions in- and ex vivo, as well as the outcomes of current
clinical trials of various retinal implants. We also briefly review alternative,
non-electronic, approaches to restoration of sight to the blind, and conclude by
suggesting some perspectives for future advancement in the field.
PMID- 27502749
TI - Neurocognitive functioning in euthymic patients with bipolar disorder and
unaffected relatives: A review of the literature.
AB - BACKGROUND: Neurocognitive deficits are present in bipolar disorder (BD) patients
and their unaffected (nonbipolar) relatives, but it is not clear which domains
are most often impaired and the extent of the impairment resulting from shared
genetic factors. In this literature review, we address these issues and identify
specific neurocognitive tasks most sensitive to cognitive deficits in patients
and unaffected relatives. METHOD: We conducted a systematic review in Web of
Science, PubMed/Medline and PsycINFO databases. RESULTS: Fifty-one articles
assessing cognitive functioning in BD patients (23 studies) and unaffected
relatives (28 studies) were examined. Patients and, less so, relatives show
impairments in attention, processing speed, verbal learning/memory, and verbal
fluency. CONCLUSION: Studies were more likely to find impairment in patients than
relatives, suggesting that some neurocognitive deficits may be a result of the
illness itself and/or its treatment. However, small sample sizes, differences
among relatives studied (e.g., relatedness, diagnostic status, age), and
differences in assessment instruments may contribute to inconsistencies in
reported neurocognitive performance among relatives. Additional studies
addressing these issues are needed.
PMID- 27502751
TI - The dlt genes play a role in antimicrobial tolerance of Streptococcus mutans
biofilms.
AB - Microbial biofilms are tolerant to antibiotic treatment and therefore cause
problematic infections. Knowledge about the molecular mechanisms underlying
biofilm-associated antimicrobial tolerance will aid the development of
antibiofilm drugs. Screening of a Streptococcus mutans transposon mutant library
for genes that are important for biofilm-associated antimicrobial tolerance
provided evidence that the dlt genes play a role in the tolerance of S. mutans
biofilms towards gentamicin. The minimum bactericidal concentration for biofilm
cells (MBC-B) for a dltA transposon mutant was eight-fold lower than that of the
wild-type. The minimum bactericidal concentration for planktonic cells (MBC-P)
was only slightly reduced, indicating that the mechanism involved in the observed
antimicrobial tolerance has a predominant role specifically in biofilms.
Experiments with a knockout dltA mutant and complemented strain confirmed that
the dlt genes in S. mutans play a role in biofilm-associated tolerance to
gentamicin. Confocal laser scanning microscopy analyses of biofilms grown on
glass slides showed that the dltA mutant produced roughly the same amount of
biofilm as the wild-type, indicating that the reduced antimicrobial tolerance of
the dltA mutant is not due to a defect in biofilm formation. The products of the
dlt genes have been shown to mediate alanylation of teichoic acids, and in
accordance the dltA mutant showed a more negatively charged surface than the wild
type, which likely is an important factor in the reduced tolerance of the dltA
mutant biofilms towards the positively charged gentamicin.
PMID- 27502752
TI - Ten key points for the appropriate use of antibiotics in hospitalised patients: a
consensus from the Antimicrobial Stewardship and Resistance Working Groups of the
International Society of Chemotherapy.
AB - The Antibiotic Stewardship and Resistance Working Groups of the International
Society for Chemotherapy propose ten key points for the appropriate use of
antibiotics in hospital settings. (i) Get appropriate microbiological samples
before antibiotic administration and carefully interpret the results: in the
absence of clinical signs of infection, colonisation rarely requires
antimicrobial treatment. (ii) Avoid the use of antibiotics to 'treat' fever: use
them to treat infections, and investigate the root cause of fever prior to
starting treatment. (iii) Start empirical antibiotic treatment after taking
cultures, tailoring it to the site of infection, risk factors for multidrug
resistant bacteria, and the local microbiology and susceptibility patterns. (iv)
Prescribe drugs at their optimal dosing and for an appropriate duration, adapted
to each clinical situation and patient characteristics. (v) Use antibiotic
combinations only where the current evidence suggests some benefit. (vi) When
possible, avoid antibiotics with a higher likelihood of promoting drug resistance
or hospital-acquired infections, or use them only as a last resort. (vii) Drain
the infected foci quickly and remove all potentially or proven infected devices:
control the infection source. (viii) Always try to de-escalate/streamline
antibiotic treatment according to the clinical situation and the microbiological
results. (ix) Stop unnecessarily prescribed antibiotics once the absence of
infection is likely. And (x) Do not work alone: set up local teams with an
infectious diseases specialist, clinical microbiologist, hospital pharmacist,
infection control practitioner or hospital epidemiologist, and comply with
hospital antibiotic policies and guidelines.
PMID- 27502753
TI - Retrospective survey of the efficacy of mandatory implementation of the Essential
Medicine Policy in the primary healthcare setting in China: failure to promote
the rational use of antibiotics in clinics.
AB - The objective of this study was to understand the impact of implementation of the
Essential Medicine Policy (EMP) on the rational use of antibiotics in primary
medical institutions in China. A retrospective survey was conducted in 39 primary
medical institutions to compare the efficacy of EMP in rational antibiotic use.
All institutions completed the survey 1 year before and 1 year after
implementation of the EMP. In particular, antibiotic use and its rationality were
closely examined. The institutions mainly dealt with common diseases, especially
non-infectious chronic diseases. Antibiotic usage was very inappropriate both
before and after EMP implementation. Before and after EMP implementation,
respectively, the median outpatient cost was US$6.34 and US$5.05, 52.50%
(2005/3819) and 53.41% (1865/3492) of the outpatient prescriptions contained
antibiotics, and 76.23% (1132/1485) and 78.83% (1106/1403) of inpatients were
administered antibiotics. In addition, 98.38% (425/432) and 97.52% (512/525) of
surgical inpatients were administered antibiotics, respectively, and 80.76%
(638/790) and 75.19% (503/669) of patients with a cold were prescribed
antibiotics, respectively. The most commonly used antibiotics were broad-spectrum
and injectable agents, including cephalosporins, fluoroquinolones and
penicillins. This profile showed little change following implementation of the
EMP. In conclusion, inappropriate antibiotic use is a serious problem in primary
medical institutions in China. Whilst enforcing the EMP reduced the cost of
medical services, it had little effect on promoting the rational use of
antibiotics.
PMID- 27502755
TI - [Atypical scurvy associated with anorexia nervosa].
AB - INTRODUCTION: Scurvy, or "Barlow's disease", is a widely described disease
involving cutaneous and mucosal lesions resulting from vitamin C deficiency.
Herein, we report a case of scurvy in a 48-year-old woman that was unusual in its
atypical cutaneous-mucosal presentation as well as its association with anorexia
nervosa. PATIENTS AND METHODS: A 48-year-old woman treated for depression for
several years was admitted to hospital for her impaired general state of health.
Over the last year, she had presented palmoplantar rash and episodes of
perimalleolar oedema. The clinical examination showed the patient to have wasting
syndrome, with a BMI of 11.9kg/m2, lower-limb oedema, palmoplantar fissures,
geographic tongue, telogen effluvium and purpuric petechiae on her right knee.
However, no gingival bleeding was noted and there was no loss of tooth enamel.
The remainder of the clinical examination was normal. Blood tests revealed
extremely low vitamin C levels without any other associated deficiencies, as well
as laboratory signs of cytolysis and anicteric cholestasis without inflammatory
syndrome. The diagnosis of anorexia nervosa was made by psychiatrists, despite
the unusual age of onset. Favorable clinical outcome was rapidly achieved via a
one-month course of vitamin C supplements at a daily dose of 1g. DISCUSSION: The
absence of classical buccal-dental symptoms and the presence of keratotic
dermatosis with fissures and ulcers on the hands and feet are atypical in scurvy;
however, this diagnosis was confirmed by the existence of purpura evoking
capillary fragility, the patient's drastically low vitamin C level and the rapid
subsidence of symptoms following treatment with oral vitamin C alone. Anorexia
nervosa was doubtless the cause of deficiency. This situation is rare and a
systematic review of the literature in Medline via PubMed showed that only three
reports of scurvy associated with mental anorexia have been published since 1975.
PMID- 27502754
TI - [Reversible posterior leukoencephalopathy syndrome in a patient presenting
granulomatosis with polyangiitis].
AB - BACKGROUND: Reversible posterior leukoencephalopathy syndrome (RPLS) is
characterised by clinical neurological features of sudden onset and brain MRI
findings such as T2/Flair white matter hyperintensities. RPLS can occur in
autoimmune diseases, and rarely in systemic vasculitis. We report a case of RPLS
in a woman presenting granulomatosis with polyangiitis (Wegener's
granulomatosis). PATIENTS AND METHODS: A 22-year-old female patient was treated
with methylprednisolone pulses for granulomatosis with polyangiitis and
neurological impairment. A few hours after the second pulse, the patient had
seizures, blindness and confusion associated with high blood pressure and acute
renal failure. MRI revealed a high-intensity area on T2-Flair weighted images of
the occipital-temporal lobes. The patient was treated with antiepileptic and
antihypertensive medications, oral steroids and cyclophosphamide; the clinical
and radiological findings proved reversible over the ensuing days. DISCUSSION:
The occurrence of RPLS in systemic vasculitis is rare. Six cases of RPLS
associated with granulomatosis and polyangiitis have been reported. It appears
important to screen for high blood pressure in patients recently treated with
corticosteroids for vasculitis as this condition may represent a precipitating
factor for RPLS.
PMID- 27502757
TI - Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated
glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of
anxiety/depression.
AB - Antidepressants increase hippocampal neurogenesis by activating the
glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal
neurogenesis, suggesting that normal GR function is crucial for hippocampal
neurogenesis. Baicalin was reported to regulate the expression of GR and
facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are
still unknown. In this study, we used the chronic corticosterone (CORT)-induced
mouse model of anxiety/depression to assess antidepressant-like effects of
baicalin and illuminate possible molecular mechanisms by which baicalin affects
GR-mediated hippocampal neurogenesis. We found that oral administration of
baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT
induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX
positive cells to restore chronic CORT-induced suppression of hippocampal
neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in
GR protein levels, the increase in GR nuclear translocation and the increase in
GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased
the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and
glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin
normalized these changes. Together, our findings suggest that baicalin improves
anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We
propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated
GR phosphorylation.
PMID- 27502756
TI - 'Atherothrombosis-associated microRNAs in Antiphospholipid syndrome and Systemic
Lupus Erythematosus patients'.
AB - MicroRNAs markedly affect the immune system, and have a relevant role in CVD and
autoimmune diseases. Yet, no study has analyzed their involvement in
atherothrombosis related to APS and SLE patients. This study intended to: 1)
identify and characterize microRNAs linked to CVD in APS and SLE; 2) assess the
effects of specific autoantibodies. Six microRNAs, involved in atherothrombosis
development, were quantified in purified leukocytes from 23 APS and 64 SLE
patients, and 56 healthy donors. Levels of microRNAs in neutrophils were lower in
APS and SLE than in healthy donors. Gene and protein expression of miRNA
biogenesis-related molecules were also reduced. Accordingly, more than 75% of
identified miRNAs by miRNA profiling were underexpressed. In monocytes, miR124a
and -125a were low, while miR-146a and miR-155 appeared elevated. Altered
microRNAs' expression was linked to autoimmunity, thrombosis, early
atherosclerosis, and oxidative stress in both pathologies. In vitro treatment of
neutrophils, monocytes, and ECs with aPL-IgG or anti-dsDNA-IgG antibodies
deregulated microRNAs expression, and decreased miRNA biogenesis-related
proteins. Monocyte transfections with pre-miR-124a and/or -125a caused reduction
in atherothrombosis-related target molecules. In conclusion, microRNA biogenesis,
significantly altered in neutrophils of APS and SLE patients, is associated to
their atherothrombotic status, further modulated by specific autoantibodies.
PMID- 27502758
TI - Environment-wide association study to identify factors associated with
hematocrit: evidence from the Guangzhou Biobank Cohort Study.
AB - PURPOSE: In randomized controlled trials reducing high hematocrit (Hct) in
patients with polycythemia vera protects against cardiovascular disease (CVD)
events, whereas increasing Hct in anemia patients causes CVD events. Hct is
influenced by environmental and lifestyle factors. Given limited knowledge
concerning the drivers of Hct, we took an agnostic approach to identify drivers
of Hct. METHODS: We used an environment-wide association study to identify
environmental and lifestyle factors associated with Hct in 20443 older Chinese
adults (mean age = 62.7 years) from the Guangzhou Biobank Cohort Study. We
evaluated the role of 25 nutrients, 40 environmental contaminants, two metals
(only available for 10405 participants), and six lifestyle factors in relation to
Hct, adjusted for sex, age, recruitment phase, and socioeconomic position.
RESULTS: In a mutually adjusted model vitamin A, serum calcium, serum magnesium,
and alcohol use were associated with higher Hct, whereas physical activity was
associated with lower Hct. CONCLUSIONS: Despite the difficulty of ascertaining
causality, finding both expected (vitamin A and physical inactivity) and novel
factors (serum calcium, serum magnesium and alcohol use) strongly associated with
Hct illustrates the utility of environment-wide association study to generate
hypotheses regarding the potential contribution of modifiable exposures to CVD.
PMID- 27502759
TI - Internet Mindfulness Meditation Intervention for the General Public: Pilot
Randomized Controlled Trial.
AB - BACKGROUND: Mindfulness meditation interventions improve a variety of health
conditions and quality of life, are inexpensive, easy to implement, have minimal
if any side effects, and engage patients to take an active role in their
treatment. However, the group format can be an obstacle for many to take
structured meditation programs. Internet Mindfulness Meditation Intervention
(IMMI) is a program that could make mindfulness meditation accessible to all
people who want and need to receive it. However, the feasibility, acceptability,
and ability of IMMI to increase meditation practice have yet to be evaluated.
OBJECTIVES: The primary objectives of this pilot randomized controlled study were
to (1) evaluate the feasibility and acceptability of IMMIs in the general
population and (2) to evaluate IMMI's ability to change meditation practice
behavior. The secondary objective was to collect preliminary data on health
outcomes. METHODS: Potential participants were recruited from online and offline
sources. In a randomized controlled trial, participants were allocated to IMMI or
Access to Guided Meditation arm. IMMI included a 1-hour Web-based training
session weekly for 6 weeks along with daily home practice guided meditations
between sessions. The Access to Guided Meditation arm included a handout on
mindfulness meditation and access to the same guided meditation practices that
the IMMI participants received, but not the 1-hour Web-based training sessions.
The study activities occurred through the participants' own computer and Internet
connection and with research-assistant telephone and email contact. Feasibility
and acceptability were measured with enrollment and completion rates and
participant satisfaction. The ability of IMMI to modify behavior and increase
meditation practice was measured by objective adherence of daily meditation
practice via Web-based forms. Self-report questionnaires of quality of life, self
efficacy, depression symptoms, sleep disturbance, perceived stress, and
mindfulness were completed before and after the intervention period via Web-based
surveys. RESULTS: We enrolled 44 adults were enrolled and 31 adults completed all
study activities. There were no group differences on demographics or important
variables at baseline. Participants rated the IMMI arm higher than the Access to
Guided Meditation arm on Client Satisfaction Questionnaire. IMMI was able to
increase home practice behavior significantly compared to the Access to Guided
Meditation arm: days practiced (P=.05), total minutes (P=.01), and average
minutes (P=.05). As expected, there were no significant differences on health
outcomes. CONCLUSIONS: In conclusion, IMMI was found to be feasible and
acceptable. The IMMI arm had increased daily meditation practice compared with
the Access to Guided Meditation control group. More interaction through staff
and/or through built-in email or text reminders may increase daily practice even
more. Future studies will examine IMMI's efficacy at improving health outcomes in
the general population and also compare it directly to the well-studied
mindfulness-based group interventions to evaluate relative efficacy. TRIAL
REGISTRATION: Clinicaltrials.gov NCT02655835;
http://clinicaltrials.gov/ct2/show/NCT02655835 (Archived by WebCite at
http://www.webcitation/ 6jUDuQsG2).
PMID- 27502760
TI - Improving conceptual and procedural knowledge: The impact of instructional
content within a mathematics lesson.
AB - BACKGROUND: Students, parents, teachers, and theorists often advocate for direct
instruction on both concepts and procedures, but some theorists suggest that
including instruction on procedures in combination with concepts may limit
learning opportunities and student understanding. AIMS: This study evaluated the
effect of instruction on a math concept and procedure within the same lesson
relative to a comparable amount of instruction on the concept alone. Direct
instruction was provided before or after solving problems to evaluate whether the
type of instruction interacted with the timing of instruction within a lesson.
SAMPLE: We worked with 180 second-grade children in the United States. METHODS:
In a randomized experiment, children received a classroom lesson on mathematical
equivalence in one of four conditions that varied in instruction type (conceptual
or combined conceptual and procedural) and in instruction order (instruction
before or after solving problems). RESULTS: Children who received two iterations
of conceptual instruction had better retention of conceptual and procedural
knowledge than children who received both conceptual and procedural instruction
in the same lesson. Order of instruction did not impact outcomes. CONCLUSIONS:
Findings suggest that within a single lesson, spending more time on conceptual
instruction may be more beneficial than time spent teaching a procedure when the
goal is to promote more robust understanding of target concepts and procedures.
PMID- 27502761
TI - Determinants of patient satisfaction and their willingness to return after
primary total hip replacement: a cross-sectional study.
AB - BACKGROUND: Surveys of patient satisfaction and their willingness to return can
be used for the optimization of processes, improving their quality, and
increasing the satisfaction and loyalty in customers. This study looked at the
factors significantly associated with patient satisfaction after primary total
hip replacement (THR), and which affect the patients' willingness to return to
the same hospital for future treatment, even when unrelated to their THR.
METHODS: Data for the study was collected by written survey from 810 patients of
43 hospitals following their THR. Satisfaction and willingness to return were
measured using a validated, multidimensional questionnaire, primarily based on
six-point scales, which were then evaluated together with routine hospital data,
according to bivariate and multivariate analyses. RESULTS: The bivariate analysis
showed a strong correlation between satisfaction or willingness to return and the
health condition before hospitalization as well as the perceived length of stay.
In contrast, the patient's gender and the number of inpatient cases in a hospital
with THR had no influence. The binary logistic regression analyses identified
three predictors associated with overall satisfaction and seven predictors
associated with willingness to return. The strongest factor for both dependent
variables was the perceived length of stay, and the weakest factor for
satisfaction was the treatment outcome. CONCLUSIONS: Overall, with all of the
medical and service-related issues considered, high levels of satisfaction were
reached. Despite the high satisfaction scores, probable causes for declining the
willingness to return were identified. The results provide incentives for
hospitals and medical professionals to attain a high satisfaction levels in their
THR patients.
PMID- 27502762
TI - Engaging members and partner organizations in translating a nursing science
agenda.
PMID- 27502763
TI - Human milk and breastfeeding: An intervention to mitigate toxic stress.
AB - The American Academy of Nursing has identified toxic stress in childhood as a
health policy concern of high priority. Adult diseases (e.g., obesity, diabetes,
hypertension and cardiovascular disease) should be viewed as developmental
disorders that begin early in life that could be reduced with the alleviation of
toxic stress in childhood. The provision of human milk/breastfeeding is an
evidence-based intervention that may hold the greatest potential to mitigate the
effects of toxic stress from the moment of birth. Assisting families to make an
informed choice to initiate and continue breastfeeding from birth has the
potential to address both the disparity in the quality of nutrition provided
infants and the economic stress experienced by families who purchase formula. The
Expert Panel on Breastfeeding endorses initiatives to improve the initiation,
duration, and exclusivity of breastfeeding to mitigate the effects of toxic
stress in this call to action for research to build the evidence to support these
critical relationships.
PMID- 27502764
TI - How fast will the registered nurse workforce grow through 2030? Projections in
nine regions of the country.
AB - BACKGROUND: After an unprecedented increase in nursing school enrollment and
graduates in the past 10 years, projected shortages of nurses have been erased at
a national level. However, nursing markets are local, and an uneven distribution
of health care providers of all types is a longstanding feature of health care in
the United States. PURPOSE: The purpose of this study was to understand how the
outlook for future registered nurse (RN) supply varies regionally across the
United States. METHODS: We apply our nursing supply model to the nine U.S. Census
Divisions to produce separate supply forecasts for each region. DISCUSSION: We
find dramatic differences in expected future growth of the nursing workforce
across U.S. regions. These range from zero expected growth in the number of RNs
per capita in New England and in the Pacific regions between 2015 and 2030 to 40%
growth in the East South Central region (Mississippi, Alabama, Tennessee,
Kentucky) and in the West South Central region (Texas, Oklahoma, Arkansas,
Louisiana). CONCLUSION: Assuming growth in the demand for RNs per population,
some regions of the United States are expected to face shortfalls in their
nursing workforce if recent trends do not change.
PMID- 27502766
TI - Mitochondrial STAT3 is negatively regulated by SOCS3 and upregulated after spinal
cord injury.
AB - Suppressor of cytokine signaling-3 (SOCS3) expression is induced by the Janus
kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling
pathway. SOCS3 then acts as a feedback inhibitor of JAK-STAT signaling. Previous
studies have shown that knocking down SOCS3 in spinal cord neurons with
Lentiviral delivery of SOCS3-targeting shRNA (shSOCS3) increased spinal cord
injury (SCI)-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr), which in
part contributed to decreased neuronal death and demyelination as well as
enhanced dendritic regeneration and protection of neuronal morphology after SCI.
However, the role of serine phosphorylation of STAT3 (P-STAT3 Ser) is in large
part undetermined. Our purposes of this study were to evaluate the expression
patterns of P-STAT3 Ser and to explore the possible role of SOCS3 in the
regulation of P-STAT3 Ser expression. Immunoblot analyses demonstrated that
Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, induced
both P-STAT3 Tyr and P-STAT3 Ser in SH-SY5Y cells. Subcellular fractionation
further revealed that P-STAT3 Ser was localized in mitochondria. Overexpression
of SOCS3 with a Lentivirus-mediated approach in SH-SY5Y cells inhibited OSM
induced P-STAT3 Ser in both cytosol and mitochondria fractions. In contrast, OSM
induced P-STAT3 Ser was further upregulated in both cytosol and mitochondria when
SOCS3 was knocked down by Lentivirus-delivered shSOCS3. Using a rat T8 spinal
cord complete transection model, we found that SCI induced upregulation of P
STAT3 Ser in the mitochondria of macrophages/microglia and neurons both rostral
and caudal to the injury site of spinal cord. Collectively, these results suggest
that SOCS3 regulation of STAT3 signaling plays critical roles in stress
conditions.
PMID- 27502767
TI - Baicalin suppresses NLRP3 inflammasome and nuclear factor-kappa B (NF-kappaB)
signaling during Haemophilus parasuis infection.
AB - Haemophilus parasuis (H. parasuis) is the causative agent of Glasser's disease, a
severe membrane inflammation disorder. Previously we showed that Baicalin (BA)
possesses anti-inflammatory effects via the NLRP3 inflammatory pathway in an LPS
challenged piglet model. However, whether BA has anti-inflammatory effects upon
H. parasuis infection is still unclear. This study investigated the anti
inflammatory effects and mechanisms of BA on H. parasuis-induced inflammatory
responses via the NF-kappaB and NLRP3 inflammasome pathway in piglet mononuclear
phagocytes (PMNP). Our data demonstrate that PMNP, when infected with H.
parasuis, induced ROS (reactive oxygen species) production, promoted apoptosis,
and initiated transcription expression of IL-6, IL-8, IL-10, PGE2, COX-2 and TNF
alpha via the NF-kappaB signaling pathway, and IL-1beta and IL-18 via the NLRP3
inflammasome signaling pathway. Moreover, when BA was administrated, we observed
a reduction in ROS production, suppression of apoptosis, and inhibition of the
activation of NF-kappaB and NLRP3 inflammasome signaling pathway in PMNP treated
with H. parasuis. To our best knowledge, this is the first example that uses
piglet primary immune cells for an H. parasuis infection study. Our data strongly
suggest that BA can reverse the inflammatory effect initiated by H. parasuis and
possesses significant immunosuppression activity, which represents a promising
therapeutic agent in the treatment of H. parasuis infection.
PMID- 27502768
TI - Infant feeding and health-related quality of life in healthy Chinese infants:
results from a prospective, observational cohort study.
AB - BACKGROUND: Infant feeding regimens, including breastfeeding, formula-feeding, or
a combination of the two, may influence infant health-related quality of life
(HRQOL). However, few studies have examined this association. METHODS: This
prospective cohort study assessed HRQOL in relation to three parent-selected
feeding regimens: exclusively breastfed (n = 136), exclusively study formula-fed
(n = 140), and mixed-fed with study formula and breast milk (n = 151). Healthy
Chinese infants were enrolled at their first normally scheduled well infant
clinic visit at age 42 days (study day 1). Parents independently chose their
infants' feeding regimens prior to recruitment into the study, with infants in
the formula and mixed-fed groups already consuming an infant formula enriched
with alpha-lactalbumin and increased sn-2 palmitate and oligofructose. The Infant
and Toddler Quality of Life Questionnaire, which includes six infant-focused and
three parent-focused concepts, was used to assess HRQOL at day 1 and at a follow
up visit 48 days later. Scores for each concept ranged from 0 to 100. Parent
quality of life (assessed using the Mental Component Summary score of the SF-12v2
Health Survey) was included in the ANCOVA model to adjust for its potential
effect on parent's perception of infant HRQOL. RESULTS: HRQOL concept scores were
high in all three study groups at both visits (mean scores 71-95). Day 1 HRQOL
scores were not significantly different between groups. At day 48, 5 of 9 HRQOL
scores were not significantly different between groups. However, scores for
Temperament and Moods, General Health Perceptions and Parent Impact-Time were
slightly but statistically significantly lower in the formula-fed group (mean
scores 75-86; all p <= 0.01) compared to the breastfed (78-90) and mixed-fed (77
91) groups. Day 48 Parent Impact-Emotional scores were also significantly lower
by a small margin (4 points; p = 0.003) in the formula-fed group compared with
the breastfed group. CONCLUSIONS: HRQOL was high in this population of healthy
infants, with only a few small differences in HRQOL concept scores observed
between breastfed, formula-fed and mixed-fed infants. These results indicate
favorable physical, mental, and social well-being in these infants and parents.
Assessment of infant HRQOL is therefore feasible and provides valuable insight
into parental perceptions of their child's health and well-being. TRIAL
REGISTRATION: ClinicalTrials.gov, NCT01370967 .
PMID- 27502770
TI - Implementing shared decision-making: consider all the consequences.
AB - BACKGROUND: The ethical argument that shared decision-making is "the right" thing
to do, however laudable, is unlikely to change how healthcare is organized, just
as evidence alone will be an insufficient factor: practice change is governed by
factors such as cost, profit margin, quality, and efficiency. It is helpful,
therefore, when evaluating new approaches such as shared decision-making to
conceptualize potential consequences in a way that is broad, long-term, and as
relevant as possible to multiple stakeholders. Yet, so far, evaluation metrics
for shared decision-making have been mostly focused on short-term outcomes, such
as cognitive or affective consequences in patients. The goal of this article is
to hypothesize a wider set of consequences, that apply over an extended time
horizon, and include outcomes at interactional, team, organizational and system
levels, and to call for future research to study these possible consequences.
MAIN ARGUMENT: To date, many more studies have evaluated patient decision aids
rather than other approaches to shared decision-making, and the outcomes measured
have typically been focused on short-term cognitive and affective outcomes, for
example knowledge and decisional conflict. From a clinicians perspective, the
shared decision-making process could be viewed as either intrinsically rewarding
and protective, or burdensome and impractical, yet studies have not focused on
the impact on professionals, either positive or negative. At interactional
levels, group, team, and microsystem, the potential long-term consequences could
include the development of a culture where deliberation and collaboration are
regarded as guiding principles, where patients are coached to assess the value of
interventions, to trade-off benefits versus harms, and assess their burdens-in
short, to new social norms in the clinical workplace. At organizational levels,
consistent shared decision-making might boost patient experience evaluations and
lead to fewer complaints and legal challenges. In the long-term, shared decision
making might lead to changes in resource utilization, perhaps to reductions in
cost, and to modification of workforce composition. Despite the gradual shift to
value-based payment, some organizations, motivated by continued income derived
from achieving high volumes of procedures and contacts, will see this as a
negative consequence. CONCLUSION: We suggest that a broader conceptualization and
measurement of shared decision-making would provide a more substantive evidence
base to guide implementation. We outline a framework which illustrates a
hypothesized set of proximal, distal, and distant consequences that might occur
if collaboration and deliberation could be achieved routinely, proposing that
well-informed preference-based patient decisions might lead to safer, more cost
effective healthcare, which in turn might result in reduced utilization rates and
improved health outcomes.
PMID- 27502769
TI - The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study
protocol for a randomised controlled trial.
AB - BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as
one quarter of elderly surgical patients, and this decline is associated with
increased morbidity and mortality. Cognition may be affected across a range of
domains, including memory, psychomotor skills, and executive function. Whilst the
exact mechanisms of cognitive change after surgery are not precisely known,
oxidative stress and subsequent neuroinflammation have been implicated. N
acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence
oxidative homeostasis, neuronal transmission, and inflammation. NAC has been
shown to reduce oxidative stress and inflammation in both human and animal
models. There is clinical evidence to suggest that NAC may be beneficial in
preventing the cognitive decline associated with both acute physiological insults
and dementia-related disorders. To date, no trials have examined perioperative
NAC as a potential moderator of postoperative cognitive changes in the noncardiac
surgery setting. METHODS AND DESIGN: This is a single-centre, randomised, double
blind, placebo-controlled clinical trial, with a between-group, repeated
measures, longitudinal design. The study will recruit 370 noncardiac surgical
patients at the University Hospital Geelong, aged 60 years or older. Participants
are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups
are stratified by age and surgery type. Participants undergo a series of
neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post
surgery. It is hypothesised that the perioperative administration of NAC will
reduce the degree of postoperative cognitive changes at early and long-term
follow-up, as measured by changes on individual measures of the neurocognitive
battery, when compared with placebo. Serum samples are taken on the day of
surgery and on day 2 post surgery to quantitate any changes in levels of
biomarkers of inflammation and oxidative stress. DISCUSSION: The PANACEA trial
aims to examine the potential efficacy of perioperative NAC to reduce the
severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery
population. This is an entirely novel approach to the prevention of postoperative
cognitive dysfunction and will have high impact and translatable outcomes if NAC
is found to be beneficial. TRIAL REGISTRATION: The PANACEA trial has been
registered with the Therapeutic Goods Administration, and the Australian New
Zealand Clinical Trials Registry: ACTRN12614000411640 ; registered on 15 April
2014.
PMID- 27502771
TI - Metabolic host responses to malarial infection during the intraerythrocytic
developmental cycle.
AB - BACKGROUND: The malarial parasite Plasmodium falciparum undergoes a complex life
cycle, including an intraerythrocytic developmental cycle, during which it is
metabolically dependent on the infected human red blood cell (RBC). To describe
whole cell metabolic activity within both P. falciparum and RBCs during the
asexual reproduction phase of the intraerythrocytic developmental cycle, we
developed an integrated host-parasite metabolic modeling framework driven by time
dependent gene expression data. RESULTS: We validated the model by reproducing
the experimentally determined 1) stage-specific production of biomass components
and their precursors in the parasite and 2) metabolite concentration changes in
the medium of P. falciparum-infected RBC cultures. The model allowed us to
explore time- and strain-dependent P. falciparum metabolism and hypothesize how
host cell metabolism alters in response to malarial infection. Specifically, the
metabolic analysis showed that uninfected RBCs that coexist with infected cells
in the same culture decrease their production of 2,3-bisphosphoglycerate, an
oxygen-carrying regulator, reducing the ability of hemoglobin in these cells to
release oxygen. Furthermore, in response to parasite-induced oxidative stress,
infected RBCs downgraded their glycolytic flux by using the pentose phosphate
pathway and secreting ribulose-5-phosphate. This mechanism links individually
observed experimental phenomena, such as glycolytic inhibition and ribulose-5
phosphate secretion, to the oxidative stress response. CONCLUSIONS: Although the
metabolic model does not incorporate regulatory mechanisms per se, alterations in
gene expression levels caused by regulatory mechanisms are manifested in the
model as altered metabolic states. This provides the model the capability to
capture complex multicellular host-pathogen metabolic interactions of the
infected RBC culture. The system-level analysis revealed complex relationships
such as how the parasite can reduce oxygen release in uninfected cells in the
presence of infected RBCs as well as the role of different metabolic pathways
involved in the oxidative stress response of infected RBCs.
PMID- 27502772
TI - Stimulation and quantification of Babesia divergens gametocytogenesis.
AB - BACKGROUND: Babesia divergens is the most common blood parasite in Europe causing
babesiosis, a tick-borne malaria-like disease. Despite an increasing focus on B.
divergens, especially regarding veterinary and human medicine, the sexual
development of Babesia is poorly understood. Development of Babesia sexual stages
in the host blood (gametocytes) plays a decisive role in parasite acquisition by
the tick vector. However, the exact mechanism of gametocytogenesis is still
unexplained. METHODS: Babesia divergens gametocytes are characterized by
expression of bdccp1, bdccp2 and bdccp3 genes. Using previously described
sequences of bdccp1, bdccp2 and bdccp3, we have established a quantitative real
time PCR (qRT-PCR) assay for detection and assessment of the efficiency of B.
divergens gametocytes production in bovine blood. We analysed fluctuations in
expression of bdccp genes during cultivation in vitro, as well as in cultures
treated with different drugs and stimuli. RESULTS: We demonstrated that all B.
divergens clonal lines tested, originally derived from naturally infected cows,
exhibited sexual stages. Furthermore, sexual commitment was stimulated during
continuous growth of the cultures, by addition of specific stress-inducing drugs
or by alternating cultivation conditions. Expression of bdccp genes was greatly
reduced or even lost after long-term cultivation, suggesting possible problems in
the artificial infections of ticks in feeding assays in vitro. CONCLUSIONS: Our
research provides insight into sexual development of B. divergens and may
facilitate the development of transmission models in vitro, enabling a more
detailed understanding of Babesia-tick interactions.
PMID- 27502773
TI - Using complexity theory to develop a student-directed interprofessional learning
activity for 1220 healthcare students.
AB - BACKGROUND: More and better interprofessional practice is predicated to be
necessary to deliver good care to the patients of the future. However,
universities struggle to create authentic learning activities that enable
students to experience the dynamic interprofessional interactions common in
healthcare and that can accommodate large interprofessional student cohorts. We
investigated a large-scale mandatory interprofessional learning (IPL) activity
for health professional students designed to promote social learning. METHODS: A
mixed methods research approach determined feasibility, acceptability and the
extent to which student IPL outcomes were met. We developed an IPL activity
founded in complexity theory to prepare students for future practice by engaging
them in a self-directed (self-organised) learning activity with a diverse team,
whose assessable products would be emergent creations. Complicated but authentic
clinical cases (n = 12) were developed to challenge student teams (n = 5 or 6).
Assessment consisted of a written management plan (academically marked) and a
five-minute video (peer marked) designed to assess creative collaboration as well
as provide evidence of integrated collective knowledge; the cohesive patient
centred management plan. RESULTS: All students (including the disciplines of
diagnostic radiology, exercise physiology, medicine, nursing, occupational
therapy, pharmacy, physiotherapy and speech pathology), completed all tasks
successfully. Of the 26 % of students who completed the evaluation survey, 70 %
agreed or strongly agreed that the IPL activity was worthwhile, and 87 % agreed
or strongly agreed that their case study was relevant. Thematic analysis found
overarching themes of engagement and collaboration-in-action suggesting that the
IPL activity enabled students to achieve the intended learning objectives.
Students recognised the contribution of others and described negotiation,
collaboration and creation of new collective knowledge after working together on
the complicated patient case studies. The novel video assessment was challenging
to many students and contextual issues limited engagement for some disciplines.
CONCLUSIONS: We demonstrated the feasibility and acceptability of a large scale
IPL activity where design of cases, format and assessment tasks was founded in
complexity theory. This theoretically based design enabled students to achieve
complex IPL outcomes relevant to future practice. Future research could establish
the psychometric properties of assessments of student performance in large-scale
IPL events.
PMID- 27502774
TI - Pericardial effusion and cardiac tamponade after ventriculoperitoneal shunt
placement: a case report.
AB - Insertion of a ventriculoperitoneal shunt is a common neurosurgical procedure in
both adult and paediatric patients. It is one of the most important treatments in
cases of hydrocephalus; however, there is a wide range of complications: the most
common complication being a shunt infection, and examples of rare complications
are shunt migrations and cardiac tamponade. Several reports of distal
ventriculoperitoneal shunt migration in different sites, including chest, right
ventricle, pulmonary artery, bowel and scrotum were published. But pericardial
effusion with cardiac tamponade and its relationship to distal
ventriculoperitoneal shunt migration into the pericardial sac has never been
reported.
PMID- 27502775
TI - Maximum surgical resection and adjuvant intensity-modulated radiotherapy with
simultaneous integrated boost for skull base chordoma.
AB - BACKGROUND: Local recurrence is common after surgical resection of clivus
chordoma. We report the results of maximum surgical resection followed by
intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB).
METHODS: We reviewed 14 consecutive clivus chordoma cases undergoing
postoperative IMRT-SIB using the institutional protocol between 2005 and 2013.
Total and near-total resections were achieved in 11 patients (78.6 %), partial in
2 patients (14.3 %), and 1 patient (7.1 %) received RT for recurrent tumor after
total resection. Gross residual or the high-risk area defined the planning target
volume (PTV)1; PTV2 was the postoperative tumor bed plus a 3-5-mm margin, and
PTV3 was PTV2 plus a 5-10 mm margin. A moderate hypofractionation schedule was
used: doses to PTV1, PTV2 and PTV3 were 3.9 Gy, 3.15 Gy and 2.8 Gy through 15
fractions for the first two patients, and the rest received 2.5 Gy, 2.2 Gy and
1.8 Gy through 25 fractions. The biologically equivalent dose in 2-Gy fractions
(EQD2) was 65-68 Gy for PTV1, 52-56 Gy for PTV2, and 44.3-44.8 Gy for PTV3.
RESULTS: Median follow-up was 41 months. Eight patients were free of disease for
median 42.5 months (range 23-91 months), four patients had stable disease for
median 60.5 months (range 39-113 months), and 1 patient showed partial response
for 38 months after RT. Local progression was seen in one patient who received
EQD2 67.8 Gy after partial resection. Estimated 5-year progression-free and
overall survival rates were 92.9 %. Surgery improved the neurologic deficit in
six patients, and IMRT-SIB was well tolerated without lasting toxicity.
CONCLUSION: Our experience suggests that maximum resection and high-dose IMRT-SIB
can achieve local control without significant morbidities.
PMID- 27502776
TI - Evaluation of a demand-creation intervention for couples' HIV testing services
among married or cohabiting individuals in Rakai, Uganda: a cluster-randomized
intervention trial.
AB - BACKGROUND: Uptake of couples' HIV counseling and testing (couples' HCT) services
remains largely low in most settings. We report the effect of a demand-creation
intervention trial on couples' HCT uptake among married or cohabiting individuals
who had never received couples' HCT. METHODS: This was a cluster-randomized
intervention trial implemented in three study regions with differing HIV
prevalence levels (range: 9-43 %) in Rakai district, southwestern Uganda, between
February and September 2014. We randomly assigned six clusters (1:1) to receive
the intervention or serve as the comparison arm using computer-generated random
numbers. In the intervention clusters, individuals attended small group, couple
and male-focused interactive sessions, reinforced with testimonies from 'expert
couples', and received invitation coupons to test together with their partners at
designated health facilities. In the comparison clusters, participants attended
general adult health education sessions but received no invitation coupons. The
primary outcome was couples' HCT uptake, measured 12 months post-baseline.
Baseline data were collected between November 2013 and February 2014 while follow
up data were collected between March and April 2015. We conducted intention-to
treat analysis using a mixed effects Poisson regression model to assess for
differences in couples' HCT uptake between the intervention and comparison
clusters. Data analysis was conducted using STATA statistical software, version
14.1. RESULTS: Of 2135 married or cohabiting individuals interviewed at baseline,
42 % (n = 846) had ever received couples' HCT. Of those who had never received
couples' HCT (n = 1,174), 697 were interviewed in the intervention clusters while
477 were interviewed in the comparison clusters. 73.6 % (n = 513) of those
interviewed in the intervention and 82.6 % (n = 394) of those interviewed in the
comparison cluster were interviewed at follow-up. Of those interviewed, 72.3 % (n
= 371) in the intervention and 65.2 % (n = 257) in the comparison clusters
received HCT. Couples' HCT uptake was higher in the intervention than in the
comparison clusters (20.3 % versus 13.7 %; adjusted prevalence ratio (aPR) =
1.43, 95 % CI: 1.02, 2.01, P = 0.04). CONCLUSION: Our findings show that a small
group, couple and male-focused, demand-creation intervention reinforced with
testimonies from 'expert couples', improved uptake of couples' HCT in this rural
setting. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02492061 . Date of
registration: June 14, 2015.
PMID- 27502777
TI - Heart involvement in systemic lupus erythematosus: a systemic review and meta
analysis.
AB - Cardiovascular diseases are one of the most important causes of the disability
and mortality in patients with systemic lupus erythematosus (SLE). The present
study examined the cardiac abnormalities in patients with SLE by
echocardiography. Case-control studies were obtained by searching PubMed MEDLINE,
Embase, and MD Consult. Systemic review and meta-analysis were performed to
assess the cardiac abnormalities based on the changes in the echocardiography in
patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy
controls were enrolled into this study. We found that patients with SLE developed
the pericardial effusion (odds ratio (OR) (95 % confidence interval (CI)) 30.52
(9.70-96.02); p < 0.00001) and the combined valvular alterations (OR (95 %CI)
11.08 (6.98-17.59); p < 0.00001). In addition, SLE patients also exhibited an
increase in the left atrial diameter (LAD) (WMD-weighted mean difference (95 %CI)
0.18 (0.06-0.29); p = 0.002), the left ventricular internal diameter in diastole
(LVDd) (WMD (95 %CI) 0.07 (0.02-0.12); p = 0.01), and the left ventricular mass
index (LVMI) (WMD (95 %CI) 5.69 (2.69-8.69); p = 0.0002). In contrast, the left
ventricular systolic function (WMD (95 %CI) -1.22 (-1.69 to -0.75); p < 0.00001)
and diastolic function including E/A ratio and E/E' ratio (WMD (95 % CI) -0.13 (
0.24 to -0.01); p = 0.04; WMD (95 % CI) 1.71 (0.43 to 2.99); p = 0.009) were
decreased in SLE patients. Patients with SLE are associated with significant
alterations in cardiac structure and function as demonstrated by
echocardiography. Data from this study suggest that echocardiographic assessment
should be considered as a part of routine examinations for SLE patients
clinically.
PMID- 27502778
TI - Aortic aneurysm associated with rheumatoid arthritis: a population-based cross
sectional study.
AB - There is substantial evidence that aortic aneurysm (AA) may be a manifestation of
several systemic rheumatic disorders. However, only several studies have assessed
the association between rheumatoid arthritis (RA) and AA. The aim of this study
was to evaluate the incidence of AA in RA patients in a case-control study. A
retrospective case-control study was performed utilizing the database of Clalit
Health Services (CHS), a large healthcare provider organization in Israel. Data
available from the CHS database included age, sex, socioeconomic status (SES),
and diagnoses of chronic diseases, including AA. Patients over the age of 20
years who were diagnosed with RA ("cases") were compared with a sample of age-
and gender-matched enrollees without RA ("controls") regarding the prevalence of
AA. Chi-square and t tests were used for univariate analysis, and a logistic
regression model was used for multivariate analysis. The study included 11,782 RA
patients and 57,973 age- and gender-matched controls. The proportion of AA was
significantly higher in RA patients (0.72 %) compared to the control group 0.49 %
(odds ratio (OR) 1.48, 95 %; confidence interval (CI) 1.15-1.88; p = 0.002). A
multivariate analysis that evaluated covariates associated with AA revealed an
independent association of AA and RA after adjustment for different factors
including age, gender, SES, and smoking status (OR 1.406, 95 %; CI 1.094-1.789; p
= 0.006). Our study has demonstrated that AA is more prevalent in patients with
RA in comparison with general population. Future large randomized studies are
important to identify cardiovascular- and disease-related risk factors for AA
formation in RA patients.
PMID- 27502779
TI - Hormone receptor status of contralateral breast cancers: analysis of data from
the US SEER population-based registries.
AB - BACKGROUND: Women diagnosed with breast cancer display higher propensity to
develop second primary cancer in the contralateral breast (CBC). Identification
of patients with increased risk of CBC and understanding relationships between
hormone receptor (HR) statuses of the first and second breast cancers is
desirable for endocrine-based prevention strategies. METHODS: Using 1992-2012
data from 13 SEER registries, the risk of developing CBC was determined as ratio
of observed and expected second breast cancers (SIR). Association between HR
statuses was examined by exploratory data analysis and multivariable logistic
regression. RESULTS: Women with ER-positive and ER-negative breast cancers have
increased risk of developing CBC with SIR values 2.09 (CI 95 = 1.97-2.21) and
2.40 (CI 95 = 2.18-2.63), respectively. ER statuses of the CBC are moderately
positively associated. In metachronous CBC, most cases with ER-positive first
cancers had ER-positive second breast cancers (81.6 %; CI 95 = 80.2-82.9 %);
however, considerable proportion of cases with ER-negative first cancers had ER
positive second cancers (48.8 %; CI 95 = 46.2-51.4 %). CONCLUSIONS: Some women
with ER-negative breast cancers may benefit from endocrine-based prevention of ER
positive CBC.
PMID- 27502780
TI - Erratum: Revealing the mechanism of passive transport in lipid bilayers via
phonon-mediated nanometre-scale density fluctuations.
PMID- 27502781
TI - Operationalising resilience in longitudinal studies: a systematic review of
methodological approaches.
AB - Over the life course, we are invariably faced with some form of adversity. The
process of positively adapting to adverse events is known as 'resilience'.
Despite the acknowledgement of 2 common components of resilience, that is,
adversity and positive adaptation, no consensus operational definition has been
agreed. Resilience operationalisations have been reviewed in a cross-sectional
context; however, a review of longitudinal methods of operationalising resilience
has not been conducted. The present study conducts a systematic review across
Scopus and Web of Science capturing studies of ageing that posited operational
definitions of resilience in longitudinal studies of ageing. Thirty-six studies
met inclusion criteria. Non-acute events, for example, cancer, were the most
common form of adversity identified and psychological components, for example,
the absence of depression, the most common forms of positive adaptation. Of the
included studies, 4 used psychometrically driven methods, that is, repeated
administration of established resilience metrics, 9 used definition-driven
methods, that is, a priori establishment of resilience components and criteria,
and 23 used data-driven methods, that is, techniques that identify resilient
individuals using latent variable models. Acknowledging the strengths and
limitations of each operationalisation is integral to the appropriate application
of these methods to life course and longitudinal resilience research.
PMID- 27502782
TI - Periodontitis is an independent risk indicator for atherosclerotic cardiovascular
diseases among 60 174 participants in a large dental school in the Netherlands.
AB - BACKGROUND: The association between periodontitis and atherosclerotic
cardiovascular diseases (ACVD) has been established in some modestly sized
studies (<10 000). Rarely, however, periodontitis has been studied directly;
often tooth loss or self-reported periodontitis has been used as a proxy measure
for periodontitis. Our aim is to investigate the adjusted association between
periodontitis and ACVD among all individuals registered in a large dental school
in the Netherlands (Academic Centre for Dentistry Amsterdam (ACTA)). METHODS:
Anonymised data were extracted from the electronic health records for all
registered patients aged >35 years (period 1998-2013). A participant was recorded
as having periodontitis based on diagnostic and treatment codes. Any affirmative
answer for cerebrovascular accidents, angina pectoris and/or myocardial
infarction labelled a participant as having ACVD. Other risk factors for ACVD,
notably age, sex, smoking, diabetes, hypertension, hypercholesterolaemia and
social economic status, were also extracted. Logistic regression analyses were
used to evaluate the adjusted associations between periodontitis and ACVD.
RESULTS: 60 174 individuals were identified; 4.7% of the periodontitis
participants (455/9730) and 1.9% of the non-periodontitis participants (962/50
444) reported ACVD; periodontitis showed a significant association with ACVD (OR
2.52; 95% CI 2.3 to 2.8). After adjustment for the confounders, periodontitis
remained independently associated with ACVD (OR 1.59; 95% CI 1.39 to 1.81). With
subsequent stratification for age and sex, periodontitis remained independently
associated with ACVD. CONCLUSIONS: This cross-sectional analysis of a large
cohort in the Netherlands of 60 174 participants shows the independent
association of periodontitis with ACVD.
PMID- 27502783
TI - Multi-site phospho-regulation of proneural transcription factors controls
proliferation versus differentiation in development and reprogramming.
AB - During development of the nervous system, it is essential to co-ordinate the
processes of proliferation and differentiation. Basic helix-loop-helix
transcription factors play a central role in controlling neuronal differentiation
and maturation as well as being components of the combinatorial code that
determines neuronal identity. We have recently shown that the ability of the
proneural proteins Ngn2 and Ascl1 to drive neuronal differentiation is inhibited
by cyclin dependent kinase-mediated multi-site phosphorylation. This limits
downstream target promoter dwell time, thus demonstrating a direct mechanistic
regulatory link between the cell cycle and differentiation machinery.Proneural
proteins are key components of transcription factor cocktails that can bring
about the direct reprogramming of human fibroblasts into neurons. Building on our
observations demonstrating that phospho-mutant proneural proteins show an
enhanced ability to drive neuronal differentiation in vivo, we see that replacing
wild-type with phospho-mutant proneural proteins in fibroblast reprogramming
cocktails significantly enhances the axonal outgrowth, branching and
electrophysiological maturity of the neurons generated. A model is presented here
that can explain the enhanced ability of dephosphorylated proneural proteins to
drive neuronal differentiation, and some unanswered questions in this emerging
area are highlighted.
PMID- 27502784
TI - Phase I trial of dose-escalating metronomic temozolomide plus bevacizumab and
bortezomib for patients with recurrent glioblastoma.
AB - The average survival time for patients with recurrent glioblastoma is between 5
and 9 months. Phase I and II trials have shown a modest survival benefit with
combination temozolomide and other chemotherapeutics. We conducted a phase I
trial of dose-escalating temozolomide with bevacizumab and the proteasome
inhibitor bortezomib for patients with recurrent disease. Three groups of three
patients were scheduled to receive daily doses of temozolomide at 25, 50, and 75
mg/m2. Fixed doses of bortezomib and bevacizumab were given at standard
intervals. Patients were monitored for dose-limiting toxicities (DLT) to
determine the maximum-tolerated dose (MTD) of temozolomide with this regimen. No
DLT were seen in the first two groups (25 and 50 mg/m2 temozolomide). One patient
in the 75 mg/m2 group experienced a grade 4 elevation of ALT and three more
patients were accrued for a total of six patients at that dose level. No other
DLT occurred, thus making 75 mg/m2 the MTD. Progression-free survival was 3.27
months for all patients and mean overall survival was 20.75 months. The MTD of
temozolomide was 75 mg/m2 in combination with bevacizumab and bortezomib for
recurrent glioblastoma. Only one patient experienced a severe (Grade 4) elevation
of ALT. This study will provide the framework for further studies to elicit
effectiveness and better determine a safety profile for this drug combination.
PMID- 27502785
TI - Postoperative surveillance of pediatric cerebellar pilocytic astrocytoma.
AB - The purpose of this study was to identify the optimal frequency and duration of
magnetic resonance imaging follow-up in children who had gross totally resected
cerebellar pilocytic astrocytomas (CPAs). Our hypothesis was that following two
MR examinations, separated by at least 3 months, showing no evidence of tumor,
gross totally resected CPAs did not recur and no further imaging follow-up was
necessary. Retrospective review of Neuro-Oncology database from 1/2000 to 7/2013
yielded 53 patients with CPAs that had preoperative imaging and >2 years post
operative imaging follow-up available. Pilocytic astrocytomas with brainstem
involvement and patients with neurofibromatosis type I were excluded.
Preoperative tumor volumes were calculated. The dates and reports of the
examinations were tabulated. The median number of follow-up examinations was 9
over a median follow-up time of 6.05 years (2.07-12.28 years). Two consecutive MR
examinations over at least a 3 month span demonstrated the smallest negative
likelihood ratio of future recurrence (0.15). There was no association of
recurrence with preoperative tumor volume. Among the 35 patients with gross total
resection of their tumor and greater than two negative follow-up examinations,
one recurrence (2.9 %) was identified, occurring 6.4 years after initial
resection. Gross totally resected pediatric CPAs can recur, but this is
exceedingly rare. Frequent surveillance (every 3-6 months) is suggested in
patients with CPAs until absence of tumor is concluded on imaging and documented
on two consecutive studies spaced at least 3 months apart. The likelihood of
recurrence thereafter is low.
PMID- 27502786
TI - Use of Antiepileptic Drugs During Pregnancy: Evolving Concepts.
AB - Although prenatal exposure to antiepileptic drugs (AEDs) is known to impart
relatively higher risks of major congenital malformations, prospective studies
have provided refined data that allow us to differentiate the risks of different
types and doses of AEDs. As the number of AED prescriptions has dramatically
increased in reproductive-aged women with a variety of neuropsychiatric
indications, the evolving concepts learned from studies in women with epilepsy
can be applied to a much larger group of pregnant women to improve child outcomes
while maintaining maternal disease control. In addition to careful selection of
the type of medication, the amount of fetal exposure at conception and in the
first trimester probably matters across all AEDs. Some AED polytherapy regimens
are not associated with a higher risk of malformations, although other outcomes
have not yet been formally studied. The individual woman's drug target
concentration should be established preconception and maintained during
pregnancy, to prevent seizure worsening. Substantial pharmacokinetic changes
occur with many of the medications during pregnancy and postpartum, and
interindividual variability supports the use of therapeutic drug monitoring for
most AEDs. During pregnancy, vigilance and close monitoring should also include
intrauterine fetal growth, obstetric complications, and neonatal complications.
Breastfeeding can provide additional neurodevelopmental benefit and should be an
option for women on AEDs. Knowledge of these key principles enhances our ability
to make treatment recommendations with resultant improved maternal and child
outcomes. Additional prospective studies are needed to further define the risk
benefit ratio across a variety of medications, dosing strategies, and
neuropsychiatric disorders.
PMID- 27502789
TI - Posterior subtenon injection of triamcinolone acetonide for pseudophakic cystoid
macular oedema.
PMID- 27502787
TI - Modeling central metabolism and energy biosynthesis across microbial life.
AB - BACKGROUND: Automatically generated bacterial metabolic models, and even some
curated models, lack accuracy in predicting energy yields due to poor
representation of key pathways in energy biosynthesis and the electron transport
chain (ETC). Further compounding the problem, complex interlinking pathways in
genome-scale metabolic models, and the need for extensive gapfilling to support
complex biomass reactions, often results in predicting unrealistic yields or
unrealistic physiological flux profiles. RESULTS: To overcome this challenge, we
developed methods and tools ( http://coremodels.mcs.anl.gov ) to build high
quality core metabolic models (CMM) representing accurate energy biosynthesis
based on a well studied, phylogenetically diverse set of model organisms. We
compare these models to explore the variability of core pathways across all
microbial life, and by analyzing the ability of our core models to synthesize ATP
and essential biomass precursors, we evaluate the extent to which the core
metabolic pathways and functional ETCs are known for all microbes. 6,600 (80 %)
of our models were found to have some type of aerobic ETC, whereas 5,100 (62 %)
have an anaerobic ETC, and 1,279 (15 %) do not have any ETC. Using our manually
curated ETC and energy biosynthesis pathways with no gapfilling at all, we
predict accurate ATP yields for nearly 5586 (70 %) of the models under aerobic
and anaerobic growth conditions. This study revealed gaps in our knowledge of the
central pathways that result in 2,495 (30 %) CMMs being unable to produce ATP
under any of the tested conditions. We then established a methodology for the
systematic identification and correction of inconsistent annotations using core
metabolic models coupled with phylogenetic analysis. CONCLUSIONS: We predict
accurate energy yields based on our improved annotations in energy biosynthesis
pathways and the implementation of diverse ETC reactions across the microbial
tree of life. We highlighted missing annotations that were essential to energy
biosynthesis in our models. We examine the diversity of these pathways across all
microbial life and enable the scientific community to explore the analyses
generated from this large-scale analysis of over 8000 microbial genomes.
PMID- 27502788
TI - Inadequate pre-operative glycaemic control in patients with diabetes mellitus
adversely influences functional recovery after total knee arthroplasty : Patients
with impaired glycaemic control exhibit poorer functional outcomes at 1-year post
arthroplasty.
AB - PURPOSE: Whilst inadequate glycaemic control is associated with an increase in
perioperative complications following total knee arthroplasty, the impact of
glycaemic control in this at-risk patient group remains ill-defined.
Identification of at-risk patients would allow targeted pre-operative glycaemic
control intervention. METHODS: One hundred consecutive patients with a diagnosis
of diabetes mellitus and one hundred age, sex and BMI matched patients without
diabetes undergoing total knee arthroplasty in a single institution were analysed
between 2008 and 2013. Inadequate glycaemic control was defined as having an
HbA1c of greater than 64 mmol/mol (8.0 % NGSP) measured within the 3 months
before surgery. Patient demographics, diabetes management and complications of
diabetes were recorded and used as explanatory variables to deliver a generalised
linear model. This allows for relationships to be defined between change in
patient-reported function (SF-36, WOMAC) and these explanatory variables.
RESULTS: The patient group with concomitant diabetes exhibited smaller
improvements in WOMAC and SF-36 physical component summary at 1 year after knee
arthroplasty. This effect was most pronounced in the subset of patients with
inadequate glycaemic control recorded in the early pre-operative period.
CONCLUSION: Patients with diabetes, particularly those with inadequate glycaemic
control, exhibit less improvement at 1 year following knee arthroplasty than
patients without diabetes mellitus. Clinical focus on modulating this factor in
this at-risk group is warranted. LEVEL OF EVIDENCE: III.
PMID- 27502790
TI - Desmoid fibromatosis: MRI features of response to systemic therapy.
AB - OBJECTIVE: Imaging criteria for measuring the response of desmoid fibromatosis to
systemic therapy are not well established. We evaluated a series of patients with
desmoids who underwent systemic therapy to document magnetic resonance imaging
(MRI) features associated with a positive clinical response. MATERIALS AND
METHODS: This Institutional Review Board-approved retrospective study included 23
patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens
included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and
nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were
categorized as progressive disease, stable, or partial response. Maximum tumor
dimension (Dmax), approximate tumor volume (VTumor), and quantitative tumor T2
hyperintensity and contrast enhancement (relative to muscle) for pre- and post
treatment MRIs were compared. RESULTS: Three lesions progressed, 5 lesions were
stable, whereas 21 showed a clinical response. Dmax decreased more in responders
(mean -11.0 %) than in stable/progressive lesions (mean -3.6 and 0 %
respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors
(RECIST 1.1) 27 out of 29 lesions were "stable," including the 3 progressive
lesions. In responders, VTumor change averaged -29.4 %, but -19.2 % and +32.5 %
in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria
14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50
54 % in partial response/stable disease, but only by 10 % in progressive lesions
(p = 0.049, t test). Changes in contrast enhancement ranged from -23 % to 0 %,
but were not statistically significant among response groups (p = 0.37). Change
in T2 hyperintensity showed a positive correlation with volumetric change (r =
0.40). CONCLUSION: Decreases in volume and T2 hyperintensity reflect the positive
response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not
sensitive to clinically determined tumor response.
PMID- 27502792
TI - Landmarks of the Frankfort horizontal plane : Reliability in a three-dimensional
Cartesian coordinate system.
AB - OBJECTIVES: The goal was to investigate whether the three-dimensional (3D)
reliability of the landmarks defining the Frankfort horizontal plane (FH) can be
enhanced by reducing variance with the help of nearby anatomical structures.
METHODS: Twenty multislice computed tomography (MSCT) datasets of evidently
symmetrical patients (11 female and 9 male patients, 6.1-16 years old) were
selected from 695 datasets archived at our department. In the 3D reconstructions,
we located the anthropometric landmarks orbitale and porion, then these were
modified with the help of frontomalare temporale, radiculare and the most
anterior border of the left and right external acoustic pore. The resultant
orbitale* and porion* reference points for the Frankfort horizontal plane were
then compared to the original landmarks. Statistical analysis was performed.
RESULTS: The superior reliability in the sagittal y-axis and in the transversal x
axis of the new reference points was confirmed. Based on the covariance matrices,
the mean maximum standard deviation (square root of the maximum eigenvalue) in
the direction of maximum variance was reduced from 0.77/0.94 mm to 0.47/0.48 mm
for left/right orbitale, and similar reductions from 0.85/0.92 mm to 0.29/0.30 mm
were noted for left/right porion (p < 0.001 for all four points). Vertical
reliability did not improve further. CONCLUSIONS: The modifications significantly
reduced the variance of the orbitale and porion landmarks, thus, clearly
increasing the three-dimensional reliability. Hence these optimized reference
points are better suited to construct the FH, which arguably is an important
spatial reference plane in orthodontics.
PMID- 27502791
TI - Growth, metabolic markers, and cognition in 8-year old children born prematurely,
follow-up of a randomized controlled trial with essential fatty acids.
AB - The study is a follow-up of a randomized, double-blinded, placebo-controlled
trial of supplementation with docosahexaenoic acid (DHA) and arachidonic acid
(AA) to 129 very low birth weight (VLBW; birth weight <1500 g) infants fed human
milk. The main hypothesis was that supplementation would affect growth, metabolic
markers, and cognitive function. The secondary aim was to describe predictors of
metabolic markers and cognitive status at follow-up. Ninety-eight children met
for 8-year follow-up with anthropometric measures, blood biomarkers, and
cognitive testing. The intervention group had significantly lower insulin-like
growth factor-1 (IGF-1) at 8 years, whereas no differences in growth or
intelligence quotient (IQ) were found. For the total cohort, weight gain during
first year of life was neither associated with BMI, metabolic markers, nor IQ at
follow-up. Blood DHA at 8 years was positively associated with IQ. CONCLUSIONS:
The study is the first long-term follow-up of a randomized controlled trial with
essential fatty acids investigating growth, metabolic factors, and IQ. IGF-1
levels were significantly lower in the intervention group at 8 years. First-year
growth was not associated with BMI, metabolic markers, or IQ at follow-up.
Current DHA status was a significant predictor of higher IQ at follow-up. WHAT IS
KNOWN: * Preterm children have increased risk of lower intelligence quotient
(IQ), reduced growth, and abnormal metabolic status. * Early intake of
docosahexaenoic acid (DHA) and arachidonic acid (AA), as well as early growth
pattern, may influence both IQ and metabolic status. What is New: * Early
intervention with DHA and AA led to reduced insulin-like growth factor-1 in blood
at 8 years of age. * Weight gain during first year of life was neither associated
with impaired metabolic markers nor improved IQ at follow-up. * Current DHA
status was a significant predictor of higher IQ at 8 years, also when maternal
education and birth weight were included in the model.
PMID- 27502793
TI - Phototherapy for Pityriasis Lichenoides in the Pediatric Population: A Review of
the Published Literature.
AB - BACKGROUND: Pityriasis lichenoides (PL) is a dermatologic disorder that manifests
in either the acute (pityriasis lichenoides et varioliformis acuta) or the
chronic form (pityriasis lichenoides chronica, also known as parapsoriasis
chronica). Traditional first-line therapy consists of corticosteroids or
antibiotics; however, these treatments are often accompanied with multiple side
effects and may be ineffective. OBJECTIVE: The goal of this study was to review
the use of phototherapy for treating PL in the pediatric population. MATERIALS
AND METHODS: We performed a systematic review of the literature in the National
Library of Medicine's PubMed database and the SCOPUS database discussing
phototherapy for treatment of PL in the pediatric population. The following
search terms were used: 'pityriasis lichenoides', 'pityriasis lichenoides
chronica', 'pityriasis lichenoides et varioliformis acuta', and 'febrile
ulceronecrotic Mucha-Habermann disease'. RESULTS: The systematic search and
screening of articles resulted in 14 articles including a total of 64 patients
with PL treated with phototherapy. Three different modalities were utilized, with
five studies using broadband ultraviolet B (BB-UVB) radiation, nine studies
utilizing narrowband UVB (NB-UVB), and two studies employing psoralen with
ultraviolet A (PUVA) therapy. Overall, the use of BB-UVB had an initial clearance
rate of 89.6 % with 23.1 % recurrence, whereas NB-UVB cleared 73 % of the lesions
with no recurrence, and PUVA therapy initially cleared 83 % of the lesions with
60 % recurrence. The side-effect profiles were similar and revealed limited
toxicity. CONCLUSION: Phototherapy shows promising results and a favorable side
effect profile in the treatment of PL. Ultimately, large randomized controlled
trials are needed to determine optimal treatments.
PMID- 27502794
TI - Relief from anxiety using complementary therapies in the perioperative period: A
principle-based concept analysis.
AB - AIMS AND OBJECTIVES: To analyze and clarify the concept of providing relief from
anxiety using complementary therapies in the perioperative period utilizing the
epistemological, pragmatic, linguistic and logical principles of a principle
based concept analysis to examine the state of the science. BACKGROUND: The
majority of patients scheduled for surgery experience anxiety in the
perioperative period. Anxiety has the potential to limit a patient's ability to
participate in his or her care throughout their hospitalization. Although
medications are the conventional medical treatment for anxiety in the
perioperative period, the addition of a complementary therapy could be an
effective holistic approach to providing relief from anxiety. DESIGN: Principle
based concept analysis. METHODS: In 2015, strategic literature searches of CINHAL
and PUBMED using keywords were performed. Fifty-six full text articles were
assessed for eligibility. RESULTS: Twelve studies were used in the final analysis
to clarify the concept of relief from anxiety using complementary therapies in
the perioperative period. CONCLUSION: This analysis has clarified the maturity
and boundaries, within the four principles of a principle-based concept analysis,
of the concept of relief from anxiety using complementary therapies in the
perioperative period. A greater understanding of relief from anxiety using
complimentary therapies in the perioperative period as an adjunct to conventional
medicine will allow perioperative nurses and anesthesia providers to modify and
specify the plan of care for their surgical patients. The use of complementary
therapies for relief in the perioperative period appears to be an area of
promising research and treatment for patients, families and providers.
PMID- 27502795
TI - Effects of Muslims praying (Salat) on EEG gamma activity.
AB - This study investigates the difference of mean gamma EEG power between actual and
mimic Salat practices in twenty healthy Muslim subjects. In the actual Salat
practice, the participants were asked to recite and performing the physical steps
in all four stages of Salat; whereas in the mimic Salat practice, they were
instructed to perform only the physical steps without recitation. The gamma power
during actual Salat was statistically higher than during mimic Salat in the
frontal and parietal regions in all stages. In the actual Salat practice, the
left hemisphere exhibited significantly higher mean gamma power in all cerebral
regions and all stages, except the central-parietal region in the sitting
position, and the frontal area in the bowing position. Increased gamma power
during Salat, possibly related to an increase in cognitive and attentional
processing, supports the concept of Salat as a focus attention meditation.
PMID- 27502796
TI - Clinical nurses' perceptions of the opportunities for using complementary
therapies in Iranian clinical settings: A qualitative study.
AB - Nurses need to use complementary therapies in their clinical practice in order to
fulfill community's needs. There are potential opportunities for using
complementary therapies in different clinical settings. This study was done to
explore nurses' perceptions of these opportunities in Iranian clinical settings.
In this qualitative study, sampling was done purposively and ended after reaching
data saturation. Semi-structured interviews were done with fifteen nurses. The
data were analyzed via the conventional content analysis approach. The
participants' perceptions fell into three main categories of 'consumer demand',
'environmental potentials', and 'optimal official regulations' from which, the
main theme of 'A potentially-supportive environment' was abstracted. The context
of Iranian clinical settings is appropriate for using complementary therapies in
nursing practice. A potentially-supportive environment automatically directs
nurses towards using such therapies. These findings can be used by nursing
managers to integrate complementary therapies into nursing practice.
PMID- 27502798
TI - Bending without breaking: A narrative review of trauma-sensitive yoga for women
with PTSD.
AB - OBJECTIVE: The purpose of this review is to evaluate the peer-reviewed empirical
evidence on the use of Trauma-Sensitive Yoga (TSY) for the treatment of women
with post-traumatic stress disorder (PTSD): specifically interpersonal trauma
such as intimate partner violence. To date, no such review has been conducted.
METHODS: Articles meeting study inclusionary criteria were identified through
electronic database searches. A total of five studies (N = 5) were selected and
reviewed. These studies included two randomized controlled trials (RCT), one
follow-up of an RCT, one quasi-experimental study, and one qualitative study.
RESULTS: There is tentative evidence to support the efficacy of TSY in reducing
PTSD, depression, and anxiety symptomatology for women with PTSD; there is also
tentative evidence confirming the feasibility of implementing TSY as an
adjunctive mental health intervention, particularly for individuals who are non
responsive to cognitive-based psychotherapies. The qualitative findings speak to
a number of benefits of yoga practice stimulated by TSY participation centering
on the phenomenon of peaceful embodiment. CONCLUSIONS: Replication of these
results using larger and more diverse samples and rigorous study designs by
independent researchers would add credibility to these findings and contribute to
the growing body of knowledge on TSY. Additionally, there is a dearth of studies
on this nascent form of therapeutic yoga. Therefore, further research is needed
to explore the potential efficacy of TSY with other types of trauma, populations,
and settings.
PMID- 27502797
TI - Massage therapy research review.
AB - In this review, massage therapy has been shown to have beneficial effects on
varying conditions including prenatal depression, preterm infants, full-term
infants, autism, skin conditions, pain syndromes including arthritis and
fibromyalgia, hypertension, autoimmune conditions including asthma and multiple
sclerosis, immune conditions including HIV and breast cancer and aging problems
including Parkinson's and dementia. Although many of the studies have involved
comparisons between massage therapy and standard treatment control groups,
several have compared different forms of massage (e.g. Swedish versus Thai
massage), and different active therapies such as massage versus exercise.
Typically, the massage therapy groups have experienced more positive effects than
the control or comparison groups. This may relate to the massage therapy
providing more stimulation of pressure receptors, in turn enhancing vagal
activity and reducing cortisol levels. Some of the researchers have assessed
physical, physiological and biochemical effects, although most have relied
exclusively on self-report measures. Despite these methodological problems and
the dearth of research from the U.S., the massage therapy profession has grown
significantly and massage therapy is increasingly practiced in traditional
medical settings, highlighting the need for more rigorous research.
PMID- 27502799
TI - Health literacy screening of patients attending a student-led osteopathy clinic:
A pilot investigation.
AB - Adequate levels of health literacy (HL) are required for patients to access
appropriate health services and develop an understanding of the options for
managing their healthcare needs. There is limited literature on HL of patients
seeking care for a musculoskeletal complaint. The present study sought to screen
the HL of patients presenting to an Australian osteopathy student-led clinic
using a single screening question 'Are you confident completing medical forms?'.
Less than 10% of patients attending the clinic were considered to have below
adequate levels of HL using this question, consistent with other work in
Australian populations. Logistic regression analysis identified that the most
significant demographic variables associated with lower HL were patients who did
not speak English at home, those with lower education levels, and those who were
less satisfied with their life. Evaluation of a patients' HL may assist
practitioners to improve patient education and management strategies.
PMID- 27502800
TI - Investigating the effect of rose essential oil in patients with primary
dysmenorrhea.
AB - OBJECTIVE: This study aimed to evaluate the effects of rose essential oil on
primary dysmenorrhea. METHODS: One hundred patients were randomly divided into
two groups; Group D received diclofenac sodium (75 mg/im) and Group A
administered diclofenac sodium with aromatherapy (2% rose essential oil). The
visual analog scale (VAS) scores in all subjects at baseline, 10th min, and 30th
min were recorded. RESULTS: When the two groups were compared before and after
the treatment, there were significant decreases in VAS values at the 10 min and
30 min compared to baseline values in both groups (p < 0.001). However, the 30th
min mean VAS value in Group D was higher than in Group A (p = 0.019). CONCLUSION:
The present study suggests that aromatherapy with rose essential oil, which is a
nonpharmacologic treatment method, as an adjuvant to conventional treatment
methods may be beneficial for pain relief in individuals with primary
dysmenorrhea.
PMID- 27502801
TI - Yoga reduces perceived stress and exhaustion levels in healthy elderly
individuals.
AB - This study investigated whether a 7-week yoga intervention could improve physical
function, perceived stress, and mental/emotional wellness in elderly
participants. METHODS: 8 participants (66.5 +/- 0.3 years) attended 2 60-min
Hatha yoga sessions/week for 7 weeks, and performed pre- and post-intervention
assessments. Balance was assessed using a 5-test battery. Flexibility was
measured by sit-and-reach and shoulder flexibility tests. Functional mobility
tests included 8-ft up-and-go, 5 chair stands, and 4-m walk. Participants
completed SF-12, exhaustion level, and Perceived Stress Scale (PSS)
questionnaires. RESULTS: SF-12 Mental Component Summary scores, exhaustion
levels, and PSS scores improved post-intervention. No differences were found for
physical function measures. CONCLUSIONS: Yoga participation can improve
mental/emotional wellness, exhaustion levels, and stress levels in elderly
individuals, even without measurable improvements in physical function.
Clinicians and health practitioners who work with the elderly should consider
yoga as a potential therapeutic modality for improving important aspects of
quality of life in this population.
PMID- 27502802
TI - Welcoming max: Increasing pediatric provider knowledge of service dogs.
AB - Service dogs have been used in the adult population for decades. Recently, there
has been a diversification in types of service dogs, specifically for the
pediatric population. Although guide dogs and mobility dogs are accepted in
society, autism assistance dogs, seizure alert and response dogs and diabetic
alert dogs are relatively new. As pediatric service dogs attract more attention,
pediatric providers need to be prepared to answer parental inquires regarding
service dog use. The pediatric provider is well equipped to identify children who
could benefit from a service dog intervention and should be able to make a
referral to a reputable service dog provider. This article presents guidance on
appropriate patient selection, making a service dog referral, and risks and
benefits involved. Pediatric providers are ideally positioned to be leaders in
implementing this evolving new assistive technology that can help to alleviate
pediatric disabilities for both the patient and family.
PMID- 27502803
TI - Training postural control and sitting in children with cerebral palsy: Kinesio
taping vs. neuromuscular electrical stimulation.
AB - OBJECTIVE: To elucidate the effects of Kinesio Taping (KT) in addition to
neurodevelopmental therapy (NDT) on posture and sitting, and to compare the
effects of KT and neuromuscular electrical stimulation (NMES). MATERIALS-METHODS:
Seventy-five children were randomized into control, KT, and NMES groups. NDT was
applied to all children 4 times a week for 4 weeks. In addition, KT and NMES were
applied to KT and NMES groups, respectively. Sitting subset of Gross Motor
Function Measure (GMFM) and kyphosis levels of the groups were analyzed by two
way mixed ANOVA. RESULTS: GMFM and kyphosis values improved significantly in all
groups (all p < 0.01), yet change levels were more prominent in the KT and NMES
groups than the control group. Moreover, NMES group showed better improvement.
CONCLUSION: KT or NMES application for four weeks in addition to NDT is effective
on improving kyphosis and sitting. Besides, NMES is more effective than KT.
PMID- 27502804
TI - Glycemic reductions following water- and land-based exercise in patients with
type 2 diabetes mellitus.
AB - PURPOSE: To assess the acute glucose responses to the first sessions of three
mesocycles of water- and land-based aerobic exercise. METHODS: The water-based
exercise group (WBE, n = 14; 54.1 +/- 9.1 years) performed deep water walking
and/or running, while the land-based exercise group (LBE, n = 11; 60.1 +/- 7.3
years) performed walking and/or running on athletic track. In the first
mesocycle, patients trained at 85-90% of their anaerobic threshold (AT) for 35
min, progressing to 90-95% of the AT in the second mesocycle, and 95-100% of the
AT in the last mesocycle. Capillary glucose was assessed before and immediately
after the first session of each mesocycle. RESULTS: There was glycemic reduction
(p < 0.001) in all sessions, with relative reductions of 19%, 29% and 24% for the
WBE and 24%, 29% and 27% for the LBE in the mesocycles 1, 2 and 3, respectively.
There were no found differences between groups and between mesocycles.
CONCLUSIONS: The acute response of blood glucose to aerobic training between 85
and 100% of the heart rate of AT is effective and independent of the environment
in which it is performed. Clinical trial reg. no. NCT01956357,
clinicaltrials.gov.
PMID- 27502805
TI - The effect of foot reflexology applied to women aged between 40 and 60 on
vasomotor complaints and quality of life.
AB - PURPOSE: This study aims to identify the effects of foot reflexology applied to
women on their vasomotor complaints and quality of life. METHODS: A randomised
controlled study was conducted with 120 women. The experimental group received
foot reflexology treatment, while the control group received nonspecific foot
massage. RESULTS: The mean scores for hot flashes, sweats, and night sweats, were
lower in the reflexology group than the control group after the practice; and the
difference between the groups was statistically significant (p < 0.001). The mean
scores for the sub-groups of the MENQOL demonstrated improvements in both groups
after the application (p < 0.001). As for the sexual domain, there was a
significant improvement in the reflexology group (p < 0.05), but no improvements
were found in the control group (p > 0.05). CONCLUSION: Results showed that
reflexology might be effective in decreasing vasomotor problems and increasing
quality of life in women in the menopausal period.
PMID- 27502806
TI - TENS and heat therapy for pain relief and quality of life improvement in
individuals with primary dysmenorrhea: A systematic review.
AB - The present systematic review aimed to synthesize evidence for the effectiveness
of TENS and heat therapy interventions from randomized trials. Six relevant
databases were searched for studies on TENS and heat therapy for primary
dysmenorrhea. Menstrual pain intensity and quality of life were the primary and
secondary outcomes respectively. The search yielded 46 citations from which six
studies on TENS and three studies on heat therapy were systematically reviewed.
On the PEDRO quality scale, the trials methodological quality was 4.8 out of 10
for TENS and 6.3 out of 10 for heat therapy. TENS and heat therapy both showed
evidence of pain reduction, but no study included quality of life as an outcome.
Meta-analysis was not possible due to substantial heterogeneity in included
studies. TENS and heat therapy show potential as adjunct remedies in the
management of primary dysmenorrhea, but rigorous high quality trials are still
needed to made conclusive recommendation.
PMID- 27502807
TI - Massage as adjuvant therapy in the management of post-cesarean pain and anxiety:
A randomized clinical trial.
AB - OBJECTIVE: The present study was conducted to determine the effect of massage on
post-cesarean pain and anxiety. METHODS: The present single-blind clinical trial
was conducted on 156 primiparous women undergone elective cesarean section. The
participants were randomly divided into three groups, including a hand and foot
massage group, a foot massage group and a control group (n = 52 per group). The
patients' intensity of pain, vital signs and anxiety level were measured before,
immediately after and 90 min after the massage. RESULTS: A significant reduction
was observed in the intensity of pain immediately and 90 min after massage (P <
0.001). Moreover, changes in some of the physiological parameters, including
blood pressure and respiration rate, were significant after massage (P < 0.001);
however, this change was not significant for pulse rate. A significant reduction
was also observed in the level of anxiety (P < 0.001) and a significant increase
in the frequency of breastfeeding (P < 0.001) after massage. CONCLUSION: As an
effective nursing intervention presenting no side-effects, hand and foot massage
can be helpful in the management of postoperative pain and stress.
PMID- 27502808
TI - Birth ball or heat therapy? A randomized controlled trial to compare the
effectiveness of birth ball usage with sacrum-perineal heat therapy in labor pain
management.
AB - OBJECTIVE: Labor pain and its management is a major concern for childbearing
women, their families and health care providers. This study aimed to investigate
the effects of two non-pharmacological methods such as birth ball and heat
therapy on labor pain relief. MATERIAL & METHODS: This randomized control trial
was undertaken on 90 primiparous women aged 18-35 years old who were randomly
assigned to two intervention (birth ball and heat) and control groups. The pain
score was recorded by using Visual Analogue Scale (VAS) before the intervention
and every 30 min in three groups until cervical dilatation reached 8 cm. RESULTS:
The mean pain severity score in the heat therapy group was less than that of in
control group at 60 and 90 min after intervention (p < 0.05). In addition there
were significantly differences between the pain scores in the birth ball group
after all three investigated times in comparison to control group. CONCLUSION:
Both heat therapy and birth ball can use as inexpensive complementary and low
risk treatment for labor pain.
PMID- 27502809
TI - Use and interest in complementary and alternative medicine among college students
seeking healthcare at a university campus student health center.
AB - BACKGROUND: There is growing data on complementary and alternative medicine (CAM)
preferences among college students. While several studies have focused on
undergraduate students, there is limited data on graduate students. MATERIALS AND
METHODS: Cross sectional analysis of undergraduate and graduate students seeking
medical care at the University of California Irvine's Student Health Center
(SHC). The survey assessed previous CAM use and preferences for future CAM use
and education. RESULTS: The majority (67.0%) had used CAM within the last year,
27.0% would use CAM for their current health condition, and 51.9% would consider
CAM for their current health condition if they were more knowledgeable. Most
respondents desired more CAM education and indicated that they would try CAM
modalities if covered under insurance. CONCLUSION: Most college students
requested more knowledge to assist in their decisions to use CAM. These findings
provide insight for health centers on the preferences of college student
patients.
PMID- 27502810
TI - Efficacy of rehabilitation with Tai Ji Quan in an Italian cohort of patients with
Fibromyalgia Syndrome.
AB - BACKGROUND: Fibromyalgia Syndrome (FMS) is characterized by musculoskeletal pain,
muscle tenderness leading to disability, impaired quality of life (QoL), fatigue
and it is accompanied by sleep disorders and psychological distress. Mind body
therapies (MBT), such as Tai Ji Quan (TJQ), use different techniques to
facilitate the ability of the mind to influence disease characteristics and
symptoms. Some studies showed that TJQ, in patients with rheumatic diseases,
particularly FMS, improved QoL, disability and psychological distress.
OBJECTIVES: To evaluate the efficacy of TJQ on disability, QoL, fatigue, sleep
and psychological distress in an Italian cohort of FMS patients. METHODS: We
enrolled 44 FMS patients: 22 patients (Experimental Group) participated to a
course of Tai Ji Quan style of (2/week for 16 weeks); 22 patients (Control Group)
participated to an educational course about FMS (2/week for 16 weeks). At
baseline (T0) and at the end of treatment (T1), patients were assessed for
disability [Fibromyalgia Impact Questionnaire (FIQ), Health Assessment
Questionnaire (HAQ)], Quality of Life [Short-Form 36 (SF36)], fatigue [Functional
Assessment of Chronic Illness-Fatigue (FACIT-F)], pain [Widespread Pain Index
(WPI)], tenderness [Tender Points (TP)], Sleep Quality [Pittsburgh Sleep Quality
Index (PSQI)] and mood disorders [Hospital Anxiety and Depression Scale (HADS)].
RESULTS: At T1 versus T0, patients of the Experimental Group showed a significant
improvement in FIQ, FACIT, SF36 (Summary Physical Index, Physical activity,
physical role, bodily pain, general health, vitality, emotional role
limitations), in WPI, TP, PSQI (total, sleep duration, and sleep disturbance) and
HADS (total score and anxiety subscale), while Patients in the Control Group did
not improve in any parameter. CONCLUSIONS: In FMS patients TJQ, if performed by
an expert physiotherapist, should be regarded as an effective rehabilitation
method.
PMID- 27502811
TI - Perceived relaxation as a function of restorative yoga combined with Reiki for
cancer survivors.
AB - AIMS & OBJECTIVES: Twenty-six cancer survivor volunteers participated in a study
of the efficacy of perceived relaxation after performing restorative yoga
combined with Reiki. RESULTS: Subjects scoring high ratings of Meaning and Peace
in life demonstrated greater perception of depth of relaxation. A comparison of
subjects receiving concurrent Reiki (19) and restorative yoga with those who only
received restorative yoga (7) showed that Reiki subjects experienced greater
perceived depth of relaxation than subjects who were not afforded the Reiki
intervention. Non-Reiki participants also showed more difficulty overcoming
intrusive fearful thoughts than the Reiki group. CONCLUSIONS: Clinical
implications suggest that patients should be screened and treated for trauma-like
symptoms including intrusive thoughts linked to anxiety and depression before
referral to complementary programs that offer meditative or relaxation
interventions.
PMID- 27502813
TI - Topical honey for the treatment of diabetic foot ulcer: A systematic review.
AB - Topical honey has been used for the treatment of wound since ancient time. But
the medical evidence proving it is limited. Hence a systematic review was
planned. An exhaustive literature search was done in PUBMED, COCHRANE, GOOGLE
using 'topical honey', 'diabetic foot ulcer', 'chronic wounds' as key words.
Literature search showed total of five clinical trials and about ten
observational studies in various part of world. Out of five clinical trials three
concluded that honey dressing is better than conventional dressing, all the
clinical trials proved safety of honey for the treatment of diabetic foot ulcer.
Observational studies included total of 320 patients which also showed safety of
honey but efficacy cannot be considered from observational studies. This review
showed that honey dressing is safer for treatment of diabetic foot ulcer but
there is insufficient good quality data to realistically conclude on the efficacy
of honey on diabetic foot ulcers.
PMID- 27502812
TI - Effects of a chair-yoga exercises on stress hormone levels, daily life
activities, falls and physical fitness in institutionalized older adults.
AB - The aim of this study was to assess the changes mediated by exercise on
activities of daily life and falls, physical fitness, salivary cortisol and alpha
amylase in older adults living in social and health care givers centers. METHODS:
Sample consisted in 35 women (83.81 +/- 6.6 years old) were divided into two
groups: chair-yoga exercises group (CY, n = 20) and control group (CG, n = 15).
All subjects were evaluated before and after 14-weeks. CY was involved in
exercise classes two times per week, while the GC did not participate in any
exercise. RESULTS: Fear of falling decreased in both groups, cortisol increased
and alpha-amylase decreased in the CG. No significant changes occurred in
physical fitness outcomes. CONCLUSION: CY practice was able to maintain the
physical fitness scores and stress hormone levels, but was not able to improve
the subject's perception on the ability to perform the instrumental activities of
daily life.
PMID- 27502814
TI - Therapeutic Touch((r)) in a geriatric Palliative Care Unit - A retrospective
review.
AB - Complementary therapies are increasingly used in palliative care as an adjunct to
the standard management of symptoms to achieve an overall well-being for patients
with malignant and non-malignant terminal illnesses. A Therapeutic Touch Program
was introduced to a geriatric Palliative Care Unit (PCU) in October 2010 with two
volunteer Therapeutic Touch Practitioners providing treatment. OBJECTIVE: To
conduct a retrospective review of Therapeutic Touch services provided to patients
in an in-patient geriatric palliative care unit in order to understand their
responses to Therapeutic Touch. METHODS: A retrospective medical chart review was
conducted on both patients who received Therapeutic Touch as well as a random
selection of patients who did not receive Therapeutic Touch from October 2010
June 2013. Client characteristics and the Therapeutic Touch Practitioners'
observations of the patients' response to treatment were collected and analyzed.
RESULTS: Patients who did not receive Therapeutic Touch tended to have lower
admitting Palliative Performance Scale scores, shorter length of stay and were
older. Based on a sample of responses provided by patients and observed by the
Therapeutic Touch practitioner, the majority of patients receiving treatment
achieved a state of relaxation or sleep. CONCLUSIONS: This retrospective chart
review suggests that implementation of a TT program for an inpatient geriatric
Palliative Care Unit is feasible, and appears to be safe, and well-tolerated.
Moreover, patient responses, as recorded in the Therapeutic Touch practitioners'
session notes, suggest beneficial effects of Therapeutic Touch for a significant
number of participants with no evidence of negative sequelae. Therefore, the use
of TT in this difficult setting appears to have potential value as an adjunct or
complementary therapy to help patients relax.
PMID- 27502815
TI - The effect of foot reflexology and back massage on hemodialysis patients' fatigue
and sleep quality.
AB - OBJECTIVE: The aim of this study is to examine the effectiveness of foot
reflexology and back massage on optimizing the sleep quality and reducing the
fatigue of hemodialysis patients. METHODS: The study includes 105 volunteer
patients who were registered at a private dialysis clinic and were receiving
hemodialysis treatment. Foot reflexology and back massage were administered to
the patients two times a week for four weeks. The Visual Analogue Scale for
Fatigue and the Pittsburg Sleep Quality Index were used to collect data. RESULTS:
The differences between the pretest and posttest score averages of the patients
on the Visual Analogue Scale for Fatigue and the Pittsburg Sleep Quality Index
were statistically significant (p < 0.001). CONCLUSION: Foot reflexology and back
massage were shown to improve the sleep quality and reduce the fatigue of
hemodialysis patients. Compared to back massage, foot reflexology was determined
to be more effective.
PMID- 27502816
TI - Yoga research review.
AB - This paper is a review of empirical studies, review and meta-analysis
publications on yoga from the last few years. The review includes
demographics/prevalence of yoga as a practice, bibliometric analyses of the yoga
publications and the use of yoga for physical fitness and cognitive function.
Most of the studies reviewed here involve yoga effects on psychiatric and medical
conditions. These include pregnancy, prenatal and postpartum depression; stress,
PTSD, anxiety, and obesity; cardiovascular conditions including hypertension;
pain syndromes including arthritis, headaches and low back pain; autoimmune
conditions including asthma, type II diabetes and multiple sclerosis; immune
conditions including HIV and breast cancer; and aging problems including balance,
osteoporosis and Parkinson's. The methods and results of those studies are
briefly summarized along with their limitations and suggestions for future
research. Basically yoga has been more effective than control and waitlist
control conditions, although not always more effective than treatment comparison
groups such as other forms of exercise. More randomized controlled studies are
needed in which yoga is compared to active exercise groups. Having established
the physical and mental health benefits of yoga makes it ethically questionable
to assign participants to inactive control groups. Shorter sessions should be
investigated for cost-effectiveness and for daily practice. Multiple physical and
physiological measures need to be added to the self-report research protocols and
potential underlying mechanisms need to be further explored. In the interim, the
studies reviewed here highlight the therapeutic effects of yoga, a practice that
could come to be called yoga therapy.
PMID- 27502817
TI - Systemic acupuncture in patients with faecal incontinence.
AB - CONTEXT: Faecal incontinence is defined as the involuntary loss of intestinal
contents (whether faeces or gas). Although it is not frequently reported, it does
cause physical and psychological distress. Traditional Chinese medicine believes
that the healthy human body is originally in a state of balanced energy (Qi)
between Yin and Yang, and all disorders that occur in the body are explained by
disruptions in this energy balance. Acupuncture is a valuable therapy and is used
as a therapeutic approach for the treatment of pelvic floor dysfunction. Data
regarding faecal incontinence and acupuncture is scarce. This research describes
the efficacy of using acupuncture in patients with faecal incontinence. PATIENTS
AND METHODS: Eighteen adults (2 men and 16 women) underwent acupuncture therapy
with traditional acupuncture needles for 10 weeks. Before and after treatment,
all patients completed a Fecal Incontinence Quality of Life (FIQL) survey and the
incontinence intensity was assessed using a visual analogue scale. RESULTS: After
10 sessions of acupuncture, all patients reported an improvement, and the vast
majority of patients showed statistically significant improvements in both tests.
CONCLUSION: Therefore, evidence now shows that acupuncture can improve the
quality of life of patients undergoing faecal incontinence treatment.
PMID- 27502818
TI - Pregnant women and health professional's perceptions of complementary alternative
medicine, and participation in a randomised controlled trial of acupressure for
labour onset.
AB - Feasibility randomised controlled trials of complementary medicine are important
to evaluate acceptability and practicality. This study examined participants' and
health professionals' perceptions of CAM and participation in a feasibility RCT
of acupressure for labour onset. METHODS: A qualitative study incorporated within
an RCT. Data were collected from postnatal women via questionnaires and health
professionals via focus groups. RESULTS: Four themes emerged from the women's
views: "Using CAM to start labour", "Feeling empowered through action", "Desiring
randomisation to acupressure group", and "Welcoming the opportunity to assist in
research". Five themes emerged from the health professionals' views: "Personal
awareness and attitudes towards CAM"; "Supporting and empowering women";
"Complements the wellness model of pregnancy and childbirth"; "Need for evidenced
based practice"; and "Randomisation 'doing it on the sly'". CONCLUSIONS: Themes
from the groups were similar. The study protocol will be refined with a placebo
group to improve equipoise with a powered RCT planned.
PMID- 27502819
TI - The therapeutic impacts of environmental design interventions on wellness in
clinical settings: A narrative review.
AB - PURPOSE: The aim of this review is to document the role of physical environmental
factors in clinical environments and their impact on patients and staff wellness
with a particular focus on physical and mental healthcare. METHODS: Data sources
comprised relevant English language articles and the results of literature search
of ISI Web of Knowledge, PubMed, Scopus, ProQuest Central, MEDLINE, and Google.
RESULTS: Incorporating physical environmental factors into hospital design can
facilitate better user satisfaction, efficiency and organisational outcomes. Many
of the design interventions convey positive distractions for patients and staff,
in terms of views of pleasant outside vistas, soothing sound, artwork and music.
CONCLUSIONS: Well-designed physical settings play an important role in the
healing process of patients in health care facilities. The challenge then is to
fully understand that role in the ecological context of health care. Other
contributors are possible and should be explored in further research.
PMID- 27502820
TI - The effect of auricular acupressure on nausea and vomiting caused by chemotherapy
among breast cancer patients.
AB - OBJECTIVE: The aim of this study was to determine the effect of auricular
acupressure in relieving nausea and vomiting among the women who received
chemotherapy. METHODS: 48 women suffering from Breast Cancer and receiving
chemotherapy were recruited for the study. The patients were randomly assigned
into two groups of experiment and control. In the initial phase of chemotherapy,
the experimental group received standard medications to control nausea and
vomiting and auricular acupressure for five days. Meanwhile, the control group
received only the standard medications. RESULTS: The use of auricular acupressure
led to the decrease in the number and intensity of nausea and vomiting in both
the acute and delayed phases in experimental group which were significantly lower
than the control group (P = 0/001). CONCLUSIONS: It is suggested that nurses use
this pressure technique as a complementary treatment, non - pharmacological,
inexpensive, non-invasive approach for the relief of chemotherapy-induced nausea
and vomiting.
PMID- 27502821
TI - Structure of the lateral mass of the ethmoid by curved stacking of endoturbinal
elements.
AB - CONTEXT: According to evo-devo theory, the embryonic development of the nasal
organ mimics its phylontogenic formation: the lateral masses of the human ethmoid
bone develop by curved "onion" stacking of the endoturbinals (the horizontal bone
septa of the mammalian olfactory chamber) under the impact of facial and skull
base remodeling, rather than by pneumatization of cavities communicating via
ostia. OBJECTIVES: To assess the frequency of the onion structure on coronal CT.
MATERIAL AND METHODS: Three independent examiners performed a retrospective
descriptive study of coronal CT scans taken ahead of septorhinoplasty between
June 2010 and December 2012 in adult patients without history of sinonasal
surgery. RESULTS: Fifty patients were included. In the anterior right and left
and posterior right ethmoid, an onion arrangement of the endoturbinals was
systematically found on at least 1 view, and on 60% of views taking all ethmoid
compartments together. Two endoturbinals were generally involved, but a rolling
up of 3 endoturbinals was also observed, significantly more frequently in the
posterior compartments (P=0.004 on the right side, P=0.012 on the left).
CONCLUSION: The onion structure of the lateral masses of the ethmoid can be
observed on coronal CT scans. This structure confirms evo-devo theory. The
ethmoid thus appears fundamentally different from the paranasal sinuses,
suggesting that the pathogenesis of nasal polyposis and ethmoidectomy techniques
need to be reconsidered.
PMID- 27502822
TI - Single-center retrospective series of fourteen patients with mucosal melanoma of
the nasal cavity and paranasal sinuses.
AB - OBJECTIVES: Mucosal melanoma of the nasal cavity and paranasal sinuses is a rare
and highly aggressive tumor. We report our experience over 20 years in management
of this tumor. PATIENTS AND METHODS: A retrospective study included 14 patients
with primary sinonasal mucosal melanoma. RESULTS: The series comprised 8 male and
6 female patients, with a median age at diagnosis of 67 years. Staging on the
American Joint Committee on Cancer classification of sinus cancer was 14% T2, 22%
T3, 75% T4a and 7% T4b. All patients underwent primary surgical treatment; 71%
received adjuvant external radiotherapy. Median recurrence-free interval was 28.7
months. Two- and 5-year overall survival was 43% and 32%, respectively. Median
follow-up was 43 months. CONCLUSIONS: Mucosal melanomas of the nasal cavity and
paranasal sinuses are very specific entities. Limited pathophysiological
knowledge still precludes effective medium- and long-term management. Future
treatment will probably be based on global adjuvant or neoadjuvant-targeted
chemotherapy.
PMID- 27502823
TI - Use of auditory steady-state responses in children and comparison with other
electrophysiological and behavioral tests.
AB - OBJECTIVE: In patients who cannot or will not cooperate in behavioral hearing
assessment, electrophysiological examinations are used, but are time-consuming
because the subject has to remain immobile. The aim of this study was to assess
whether auditory steady-state responses (ASSR) are sufficiently reliable,
compared to auditory brainstem responses (ABR) and free-field audiometry, for
assessment to begin with ASSR instead of ABR. MATERIAL AND METHODS: A
retrospective study was performed between January 2012 and April 2013, including
children less than 6 years of age who could not be tested via headphones. ASSR
and ABR were measured during natural sleep or under phenobarbital-alimemazine
sedation. Subjective pure-tone audiometry was performed, using the visual
reinforcement audiometry method, in 69 children who were able and willing to
cooperate. RESULTS: A total of 175 children were included. ASSR and ABR
thresholds showed good positive correlation (338 ears; Pearson's correlation
coefficient, 0.87). Behavioral thresholds correlated significantly with ASSR
thresholds (Student t-test for matched series; P<0.05). ASSR thresholds were
usually better than behavioral thresholds, with a difference of 8-15dB HL.
CONCLUSION: ASSR is reliable in children under 6 years of age, and should be
performed before ABR when hearing threshold rather than latency is to be
determined.
PMID- 27502824
TI - Exoskeletal cuticle of cavernicolous and epigean terrestrial isopods: A review
and perspectives.
AB - Comparative ultrastructural studies of the integument in terrestrial isopod
crustaceans show that specific environmental adaptations of different eco
morphotypes are reflected in cuticle structure. The biphasic molting in isopods
is a valuable experimental model for studies of cuticular matrix secretion and
degradation in the same animal. The aim of this review is to show structural and
functional adaptations of the tergal cuticle in terrestrial isopods inhabiting
cave habitats. Exoskeletal cuticle thickness, the number of cuticular layers,
epicuticle structure, mineralization, pigmentation and complexity of sensory
structures are compared, with greater focus on the well-studied cave trichoniscid
Titanethes albus. A large number of thinner cuticular layers in cave isopods
compared to fewer thicker cuticular layers in related epigean species of similar
body-sizes is explained as a specific adaptation to the cavernicolous life style.
The epicuticle structure and composition are compared in relation to their
potential waterproofing capacity in different environments. Cuticle
mineralization is described from the functional point of view as well as from the
aspect of different calcium storage sites and calcium dynamics during the molt
cycle. We also discuss the nature and reduction of pigmentation in the cave
environment and outline perspectives for future research.
PMID- 27502825
TI - Angiotensin-converting enzyme inhibitor-associated angioedema treated with c1
esterase inhibitor: A case report and review of the literature.
AB - CASE REPORT: A 59-year old man currently on >5 years of angiotensin-converting
enzyme inhibitor (ACEI) therapy presented to the emergency department with
angioedema of the tongue and difficulty swallowing. After receiving conventional
therapy of antihistamine, steroids, and epinephrine, the patient's condition
continued to deteriorate, with imminent intubation. The patient was treated with
a C1-esterase inhibitor (C1-INH) and experienced rapid resolution of symptoms,
which avoided airway complications. DISCUSSION: Although no therapy has been
approved for the treatment of ACEI-associated angioedema (AAE), the conventional
therapy (antihistamine, steroids, and epinephrine) often proves ineffective in
this bradykinin-mediated angioedema. There are drugs approved and used for
hereditary angioedema that may be effective in the acute phase of ACEI-AAE that
may prevent the need for further interventions, such as intubation and
tracheotomy. These drugs include icatibant, ecallantide, fresh frozen plasma, and
C1-INH. CONCLUSION: The literature and clinical evidence indicate C1-INH can be
effectively used in the treatment of ACEI-AAE to halt the progression of the
condition, prevent airway compromise and the need for intervention, and lead to
rapid resolution of symptoms.
PMID- 27502826
TI - The Role of Trace Elements in Tinnitus.
AB - In this study, we aimed to investigate the role of three trace elements, namely,
zinc, copper, and lead, in tinnitus by analyzing the serum level of copper and
lead and both the serum and tissue level of zinc. Eighty patients, who applied to
outpatient otolaryngology clinic with the complaints of having tinnitus, and 28
healthy volunteers were included. High-frequency audiometry was performed, and
participants who had hearing loss according to the pure tone average were
excluded; tinnitus frequency and loudness were determined and tinnitus reaction
questionnaire scores were obtained from the patients. Of all the participants,
serum zinc, copper, and lead values were measured; moreover, zinc levels were
examined in hair samples. The levels of trace elements were compared between
tinnitus and control groups. The level of copper was found to be significantly
lower in the tinnitus group (p = 0.02), but there was no significant difference
between the groups in terms of the levels of zinc, neither in serum nor in hair,
and lead in serum (p > 0.05). The lack of trace elements, especially that of
"zinc," have been doubted for the etiopathogenesis of tinnitus in the literature;
however, we only found copper levels to be low in patients having tinnitus.
PMID- 27502828
TI - Attitudes to diagnosis and management in dementia care: views of future general
practitioners.
AB - Considerable international governmental support is focused on the timely
diagnosis of dementia and post-diagnostic care of people with dementia.
Identifying those at high risk of dementia is one approach to timely diagnosis.
General practitioners (GPs) are well-placed clinicians in the community to
provide both pre- and post-diagnostic dementia care. However, GPs have in the
past consistently demonstrated low confidence in both diagnosing dementia and
providing care for these complex patients particularly for patients in the post
diagnostic phase. It is currently unclear how future GPs view dementia care. We
aimed to evaluate the current attitudes and experiences of future GPs in dementia
care and their views on targeting high risk groups. All (n = 513) GP trainees
were approached by email to participate in a cross-sectional web and paper-based
survey in the North of England. A further reminder was sent out two months after
the initial invitation. We received 153 responses (29.8% response rate, 66.7%
female, average age 31 (range 25-55 years old). The main difficulties encountered
included coordinating supporting services for carers and the person with dementia
and responding to co-existing behavioral and psychiatric symptoms. Further
education in dementia management was considered to be important by respondents.
GP trainees were generally very positive about their future role in caring for
people with dementia, particularly in the area of earlier diagnosis via
identification of high-risk individuals. Future GPs in one area of England are
very positive about their key role in dementia care. In order to facilitate the
delivery of high quality, community-based care, work is required to establish
core post-diagnostic dementia support services. Further research is needed to
identify effective systems to enable accurate assessment and to ensure earlier
diagnosis in high-risk groups.
PMID- 27502827
TI - Dietary pattern transitions, and the associations with BMI, waist circumference,
weight and hypertension in a 7-year follow-up among the older Chinese population:
a longitudinal study.
AB - BACKGROUND: Few studies explored the effects of nutritional changes on body mass
index (BMI), weight (Wt), waist circumference (WC) and hypertension, especially
for the older Chinese population. METHODS: By using China Health and Nutrition
Survey 2004-2011 waves, a total of 6348 observations aged >= 60 were involved in
the study. The number of participants dropped from 2197 in 2004, to 1763 in 2006,
1303 in 2009, and 1085 in 2011. Dietary information was obtained from
participants using 24 hour-recall over three consecutive days. Height, Wt, WC,
systolic and diastolic blood pressure were also measured in each survey year. The
dietary pattern was derived by exploratory factor analysis using principal
component analysis methods. Linear Mixed Models were used to investigate
associations of dietary patterns with BMI, Wt and WC. Generalized Estimating
Equation models were used to assess the associations between dietary patterns and
hypertension. RESULTS: Over time, older people's diets were shifting towards a
modern dietary pattern (high intake of dairy, fruit, cakes and fast food).
Traditional and modern dietary patterns had distinct associations with BMI, Wt
and WC. Participants with a diet in the highest quartile for traditional
composition had a beta (difference in mean) of -0.23 (95 % CI: -0.44; -0.02) for
BMI decrease, beta of -0.90 (95 % CI: -1.42; -0.37) for Wt decrease; and beta of
1.57 (95 % CI: -2.32; -0.83) for WC decrease. However, participants with a diet
in the highest quartile for modern diet had a beta of 0.29 (95 % CI: 0.12; 0.47)
for BMI increase; beta of 1.02 (95 % CI: 0.58; 1.46) for Wt increase; and beta of
1.44 (95 % CI: 0.78; 2.10) for Wt increase. No significant associations were
found between dietary patterns and hypertension. CONCLUSIONS: We elucidate the
associations between dietary pattern and change in BMI, Wt, WC and hypertension
in a 7-year follow-up study. The strong association between favourable body
composition and traditional diet, compared with an increase in BMI, WC and Wt
with modern diet suggests that there is an urgent need to develop age-specific
dietary guideline for older Chinese people.
PMID- 27502829
TI - Differentiating sibling species of Zeugodacus caudatus (Insecta: Tephritidae) by
complete mitochondrial genome.
AB - Zeugodacus caudatus is a pest of pumpkin flowers. It has a Palearctic and
Oriental distribution. We report here the complete mitochondrial genome of the
Malaysian and Indonesian samples of Z. caudatus determined by next-generation
sequencing of genomic DNA and determine their taxonomic status as sibling species
and phylogeny with other taxa of the genus Zeugodacus. The whole mitogenome of
both samples possessed 37 genes (13 protein-coding genes-PCGs, 2 rRNA and 22 tRNA
genes) and a control region. The mitogenome of the Indonesian sample (15,885 bp)
was longer than that of the Malaysian sample (15,866 bp). In both samples, TPsiC
loop was absent in trnF and DHU-loop was absent in trnS1. Molecular phylogeny
based on 13 PCGs was concordant with 15 mitochondrial genes (13 PCGs and 2 rRNA
genes), with the two samples of Z. caudatus forming a sister group and the genus
Zeugodacus was monophyletic. The Malaysian and Indonesian samples of Z. caudatus
have a genetic distance of p = 7.8 % based on 13 PCGs and p = 7.0 % based on 15
mitochondrial genes, indicating status of sibling species. They are proposed to
be accorded specific status as members of a species complex.
PMID- 27502830
TI - Introduction to Special Issue on Mitochondrial Redox Signaling in Health and
Disease.
PMID- 27502831
TI - Community Federally Qualified Health Centers as Homes for HIV Preexposure
Prophylaxis: Perspectives from South Florida.
AB - Preexposure prophylaxis (PrEP) for HIV has the potential to reduce HIV incidence
in highly affected areas. The Southeastern United States is disproportionately
impacted by HIV, and 3 counties in South Florida have the highest incidence of
new HIV infections in the United States. This study explored the feasibility,
acceptability, and uptake of PrEP in South Florida. Focus groups consisting of
providers, administrators, and case managers at HIV-servicing community health
centers and federally qualified health centers in South Florida reported broad
support but low implementation of PrEP. Generally, participants indicated that
the centers were appropriate locations for implementation. However, practical
concerns and perceived limitations due to financial, insurance, and immigration
status of those who would potentially benefit from the intervention were widely
reported. Addressing provider concerns appears necessary for successful expansion
of PrEP implementation in highly impacted areas such as South Florida.
PMID- 27502832
TI - Association Between Monetary Deposits and Weight Loss in Online Commitment
Contracts.
AB - PURPOSE: To examine the characteristics of voluntary online commitment contracts
that may be associated with greater weight loss. DESIGN: Retrospective analysis
of weight loss commitment contracts derived from a company that provides web
based support for personal commitment contracts. Using regression, we analyzed
whether percentage weight loss differed between participants who incentivized
their contract using monetary deposits and those who did not. SETTING: Online.
PARTICIPANTS: Users (N = 3857) who voluntarily signed up online in 2013 for a
weight loss contract. INTERVENTION: Participants specified their own weight loss
goal, time period, and self-reported weekly weight. Deposits were available in
the following 3 categories: charity, anticharity (a nonprofit one does not like),
or donations made to a friend. MEASURES: Percentage weight loss per week.
ANALYSIS: Multivariable linear regressions. RESULTS: Controlling for several
participant and contract characteristics, contracts with anticharity, charity,
and friend deposits had greater reported weight loss than nonincentivized
contracts. Weight change per week relative to those without deposits was -0.33%,
0.28%, and -0.25% for anti-charity, charity, and friend, respectively ( P <
0.001). Contracts without a weight verification method claimed more weight loss
than those with verification. CONCLUSION: Voluntary use of commitment contracts
may be an effective tool to assist weight loss. Those who choose to use monetary
incentives report more weight loss. It is not clear whether this is due to the
incentives or higher motivation.
PMID- 27502834
TI - Biomanufacture of nano-Pd(0) by Escherichia coli and electrochemical activity of
bio-Pd(0) made at the expense of H2 and formate as electron donors.
AB - OBJECTIVE: Palladised cells of Desulfovibrio desulfuricans and Shewanella
oneidensis have been reported as fuel cell electrocatalysts but growth at scale
may be unattractive/costly; we have evaluated the potential of using E. coli,
using H2/formate for Pd-nanoparticle manufacture. RESULTS: Using 'bio-Pd' made
under H2 (20 wt%) cyclic voltammograms suggested electrochemical activity of bio
NPs in a native state, attributed to proton adsorption/desorption. Bio-Pd
prepared using formate as the electron donor gave smaller, well separated NPs;
this material showed no electrochemical properties, and hence little potential
for fuel cell use using a simple preparation technique. Bio-Pd on S. oneidensis
gave similar results to those obtained using E. coli. CONCLUSION: Bio-Pd is
sufficiently conductive to make an E. coli-derived electrochemically active
material on intact, unprocessed bacterial cells if prepared at the expense of H2,
showing potential for fuel cell applications using a simple one-step preparation
method.
PMID- 27502833
TI - A/T Run Geometry of B-form DNA Is Independent of Bound Methyl-CpG Binding Domain,
Cytosine Methylation and Flanking Sequence.
AB - DNA methylation in a CpG context can be recognised by methyl-CpG binding protein
2 (MeCP2) via its methyl-CpG binding domain (MBD). An A/T run next to a methyl
CpG maximises the binding of MeCP2 to the methylated DNA. The A/T run
characteristics are reported here with an X-ray structure of MBD A140V in complex
with methylated DNA. The A/T run geometry was found to be strongly stabilised by
a string of conserved water molecules regardless of its flanking nucleotide
sequences, DNA methylation and bound MBD. New water molecules were found to
stabilise the Rett syndrome-related E137, whose carboxylate group is salt bridged
to R133. A structural comparison showed no difference between the wild type and
MBD A140V. However, differential scanning calorimetry showed that the melting
temperature of A140V constructs in complex with methylated DNA was reduced by ~7
degrees C, although circular dichroism showed no changes in the secondary
structure content for A140V. A band shift analysis demonstrated that the larger
fragment of MeCP2 (A140V) containing the transcriptional repression domain (TRD)
destabilises the DNA binding. These results suggest that the solution structure
of MBD A140V may differ from the wild-type MBD although no changes in the
biochemical properties of X-ray A140V were observed.
PMID- 27502835
TI - Expression of a high sweetness and heat-resistant mutant of sweet-tasting
protein, monellin, in Pichia pastoris with a constitutive GAPDH promoter and
modified N-terminus.
AB - OBJECTIVES: To improve the stability and sweetness of the sweet-tasting protein,
monellin, by using site-directed mutagenesis and a Pichia pastoris expression
system with a GAPDH constitutive promoter. RESULTS: Both wild-type and E2 N
mutant of single-chain monellin gene were cloned into the PGAPZalphaA vector and
expressed in Pichia pastoris. The majority of the secreted recombinant protein,
at 0.15 g/l supernatant, was monellin. This was purified by Sephadex G50
chromatography. The sweetness threshold of wild-type and E2 N were 30 MUg/ml and
20 MUg/ml, respectively. Compared with the proteins expressed in Escherichia
coli, the thermostability of both proteins was improved. The N-terminal sequence
is determinative for the sweetness of the proteins expressed in yeast strains.
CONCLUSIONS: Site-directed mutagenesis, modification of the N-terminus of
monellin, and without the need of methanol induction in P. pastoris expression
system, indicate the possibility for large-scale production of this sweet-tasting
protein.
PMID- 27502836
TI - Solving the "Personhood Jigsaw Puzzle" in Residential Care Homes for the Elderly
in the Hong Kong Chinese Context.
AB - End-of-life care studies on the nature of personhood are bourgeoning; however,
the practices utilized for achieving personhood in end-of-life care, particularly
in a cultural context in which interdependent being and collectivism prevail,
remain underexplored. This study seeks to examine and conceptualize good
practices for achieving the personhood of the dying elderly in residential care
homes in a Chinese context. Twelve interviews were conducted with both medical
and social care practitioners in four care homes to collect narratives of
practitioners' practices. Those narratives were utilized to develop an "end-of
life case graph." Constant comparative analysis led to an understanding of the
practice processes, giving rise to a process model of "solving the personhood
jigsaw puzzle" that includes "understanding the person-in-relationship and person
in-time," "identifying the personhood-inhibiting experiences," and "enabling
personalized care for enhanced psychosocial outcomes." Findings show how the
"relational personhood" of the elderly can be maintained when physical
deterioration and even death are inevitable.
PMID- 27502838
TI - Sixth International AFM BioMed Conference on AFM in life sciences and medicine,
December 13 to 17, 2014, San Diego, California.
PMID- 27502837
TI - Classical Galactosaemia and CDG, the N-Glycosylation Interface. A Review.
AB - Classical galactosaemia is a rare disorder of carbohydrate metabolism caused by
galactose-1-phosphate uridyltransferase (GALT) deficiency (EC 2.7.7.12). The
disease is life threatening if left untreated in neonates and the only available
treatment option is a long-term galactose restricted diet. While this is
lifesaving in the neonate, complications persist in treated individuals, and the
cause of these, despite early initiation of treatment, and shared GALT genotypes
remain poorly understood. Systemic abnormal glycosylation has been proposed to
contribute substantially to the ongoing pathophysiology. The gross N
glycosylation assembly defects observed in the untreated neonate correct over
time with treatment. However, N-glycosylation processing defects persist in
treated children and adults.Congenital disorders of glycosylation (CDG) are a
large group of over 100 inherited disorders affecting largely N- and O
glycosylation.In this review, we compare the clinical features observed in
galactosaemia with a number of predominant CDG conditions.We also summarize the N
glycosylation abnormalities, which we have described in galactosaemia adult and
paediatric patients, using an automated high-throughput HILIC-UPLC analysis of
galactose incorporation into serum IgG with analysis of the corresponding N
glycan gene expression patterns and the affected pathways.
PMID- 27502840
TI - Molybdenum carbide nanotubes: a novel multifunctional material for label-free
electrochemical immunosensing.
AB - Herein, a multifunctional nanoarchitecture has been developed by integrating well
crystalline molybdenum carbide (Mo2C) nanotubes and an electrochemical indicator
thionin (TH). The Mo2C nanotubes were synthesized through the self-degradable
template method and high-temperature calcination, and their structure and
morphology were characterized through scanning electron microscopy (SEM), X-ray
diffraction (XRD) and transmission electron microscopy (TEM). Due to the high
electrocatalytic properties, excellent conductivity and highly active surface
area of Mo2C nanotubes, the Mo2C-based material was used as a nanocarrier to load
TH molecules for the development of a label-free electrochemical immunosensor for
alpha-fetoprotein (AFP) detection. The decorated TH probe on the Mo2C nanotubes
not only acted as a bridging molecule to effectively capture and immobilize
primary anti-AFP on the Mo2C nanotubes, but also acted as a signal indicator for
the detection of AFP. The proposed immunosensor exhibited excellent selectivity
(with a detection limit of 3 pg mL(-1)), high stability and good reproducibility
by combining the unique structure and features of the Mo2C nanotubes.
Furthermore, this sensing platform was finally used for the detection of AFP in
human serum with satisfactory results. Therefore, the Mo2C nanotubes can be
considered as a candidate carbon material for fabrication of simple, label-free
and ultrasensitive electrochemical sensors, broadening the application of this
material.
PMID- 27502839
TI - The role of mTOR signalling in the regulation of skeletal muscle mass in a rodent
model of resistance exercise.
AB - Resistance exercise (RE) activates signalling by the mammalian target of
rapamycin (mTOR), and it has been suggested that rapamycin-sensitive mTOR
signalling controls RE-induced changes in protein synthesis, ribosome biogenesis,
autophagy, and the expression of peroxisome proliferator gamma coactivator 1
alpha (PGC-1alpha). However, direct evidence to support the aforementioned
relationships is lacking. Therefore, in this study, we investigated the role of
rapamycin-sensitive mTOR in the RE-induced activation of muscle protein
synthesis, ribosome biogenesis, PGC-1alpha expression and hypertrophy. The
results indicated that the inhibition of rapamycin-sensitive mTOR could prevent
the induction of ribosome biogenesis by RE, but it only partially inhibited the
activation of muscle protein synthesis. Likewise, the inhibition of rapamycin
sensitive mTOR only partially blocked the hypertrophic effects of chronic RE.
Furthermore, both acute and chronic RE promoted an increase in PGC-1alpha
expression and these alterations were not affected by the inhibition of rapamycin
sensitive mTOR. Combined, the results from this study not only establish that
rapamycin-sensitive mTOR plays an important role in the RE-induced activation of
protein synthesis and the induction of hypertrophy, but they also demonstrate
that additional (rapamycin-sensitive mTOR-independent) mechanisms contribute to
these fundamentally important events.
PMID- 27502841
TI - Conductive Carbon Network inside a Sulfur-Impregnated Carbon Sponge: A
Bioinspired High-Performance Cathode for Li-S Battery.
AB - A highly conductive sulfur cathode is crucial for improving the kinetic
performance of a Li-S battery. The encapsulation of sulfur in porous nanocarbons
is expected to benefit the Li(+) migration, yet the e(-) conduction is still to
be improved due to a low graphitization degree of a conventional carbon
substrate, especially that pyrolyzed from carbohydrates or polymers. Aiming at
facilitating the e(-) conduction in the cathode, here we propose to use ketjen
black, a highly graphitized nanocarbon building block to form a conductive
network for electrons in a biomass-derived, hierarchically porous carbon sponge
by a easily scaled-up approach at a low cost. The specifically designed carbon
host ensures a high loading and good retention of active sulfur, while also
provides a faster electron transmission to benefit the lithiation/delithiation
kinetics of sulfur. The sulfur cathode prepared from the carbon network shows
excellent cycling and rate performance in a Li-S battery, rendering its
practicality for emerging energy storage opportunities such as grids or
automobiles.
PMID- 27502842
TI - Risks of undernutrition and malnutrition in hospitalized pediatric patients with
spinal cord injury.
AB - STUDY DESIGN: Prospective study. OBJECTIVES: To describe the nutritional
risk/status of Chinese children with spinal cord injury (SCI) at admission and
determine the relationship between nutritional risk/status and demography/SCI
characteristics. SETTING: China Rehabilitation Research Center, Beijing, China.
METHODS: Baseline clinical data, appetite level, anthropometric measurements and
Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) scores
were obtained for pediatric SCI patients. The relationships among the
demographic/SCI characteristics and STAMP score and z-scores of weight-for-age
(WAZ), height-for-age (HAZ) and body mass index-for-age (BAZ) were assessed. The
risk of undernutrition was compared with actual nutritional status. RESULTS:
Forty-five children including 12 boys and 33 girls were included. The risks of
undernutrition using the STAMP tool and malnutrition were 51.1% and 55.6%,
respectively. Children with different demographic characteristics had similar
nutritional status and risk of malnutrition. The risk of undernutrition was
associated with nutritional status, including WAZ (P<0.001), HAZ (P=0.001), BAZ
(P<0.001) and appetite level (P<0.001). Compared with nutritional status, STAMP
had a sensitivity of 100%, a specificity of 73.3% and an overall agreement of
82.2%. As the duration of SCI increased, the risks of overweight and stunting
increased. CONCLUSIONS: Nutritional screening in all pediatric SCI patients
should be performed periodically. The decreasing trends in nutritional status and
appetite level after SCI require special attention. The STAMP may be an
alternative method for assessing nutritional status in Chinese children with SCI.
PMID- 27502843
TI - Chronic abdominal pain in long-term spinal cord injury: a follow-up study.
AB - STUDY DESIGN: A longitudinal postal survey. OBJECTIVES: To evaluate the
prevalence and characteristics of abdominal pain in long-term spinal cord injury
(SCI). SETTING: Members of the Danish SCI Association. METHODS: In 2006, a
questionnaire on chronic abdominal pain and discomfort was sent to the 284
members of the Danish SCI association who had been members for at least 10 years;
203 of them responded. An almost identical questionnaire including questions on
intensity and interference of pain within the past 7 days, as well as descriptors
and treatment, was sent to the 178 surviving members in 2015. RESULTS: Of 130
(73%) responders, 125 answered the question on chronic abdominal pain. The mean
time since injury was 30.5 (9.8) years. Chronic abdominal pain or discomfort was
reported by 32.8% (41/125), and 23% (29/125) of responders had been at least
moderately bothered by this in the past week. Abdominal pain or discomfort was
more common in women and in those with self-reported constipation. The median
intensity (numeric rating scale) was 6.0 (range 3-10) and it was often associated
with autonomic symptoms. Nine (8%) of the 115 individuals who responded in both
2006 and 2015 had developed new abdominal pain or discomfort, 30 (26%) no longer
reported it, and 28 (24%) reported it at both time points with a similar
intensity. CONCLUSIONS: Chronic abdominal pain or discomfort is common and
bothersome in long-term SCI. It has a late onset, but the prevalence and severity
do not seem to further increase between 20 and 30 years following SCI.
PMID- 27502844
TI - Mode jumping of split-ring resonator metamaterials controlled by high
permittivity BST and incident electric fields.
AB - We investigate the resonant modes of split-ring resonator (SRR) metamaterials
that contain high-permittivity BST block numerically and experimentally. We
observe interesting mode-jumping phenomena from the BST-included SRR absorber
structure as the excitation wave is incident perpendicularly to the SRR plane.
Specifically, when the electric field is parallel to the SRR gap, the BST block
in the gap will induce a mode jumping from the LC resonance to plasmonic
resonance (horizontal electric-dipole mode), because the displacement current
excited by the Mie resonance in the dielectric block acts as a current channel in
the gap. When the electric field is perpendicular to the gap side, the plasmonic
resonance mode (vertical electric-dipole mode) in SRR changes to two joint modes
contributed simultaneously by the back layer, SRR and BST block, as a result of
connected back layer and SRR layer by the displacement current in the BST
dielectric block. Based on the mode jumping effect as well as temperature and
electric-field dependent dielectric constant, the BST-included SRR metamaterials
may have great potentials for the applications in electromagnetic switches and
widely tunable metamaterial devices.
PMID- 27502845
TI - Permutation-based inference for the AUC: A unified approach for continuous and
discontinuous data.
AB - We investigate rank-based studentized permutation methods for the nonparametric
Behrens-Fisher problem, that is, inference methods for the area under the ROC
curve. We hereby prove that the studentized permutation distribution of the
Brunner-Munzel rank statistic is asymptotically standard normal, even under the
alternative. Thus, incidentally providing the hitherto missing theoretical
foundation for the Neubert and Brunner studentized permutation test. In
particular, we do not only show its consistency, but also that confidence
intervals for the underlying treatment effects can be computed by inverting this
permutation test. In addition, we derive permutation-based range-preserving
confidence intervals. Extensive simulation studies show that the permutation
based confidence intervals appear to maintain the preassigned coverage
probability quite accurately (even for rather small sample sizes). For a
convenient application of the proposed methods, a freely available software
package for the statistical software R has been developed. A real data example
illustrates the application.
PMID- 27502846
TI - Albuminuria and cardiovascular events in patients with acute coronary syndromes:
Results from the TRACER trial.
AB - BACKGROUND: Albuminuria is associated with cardiovascular (CV) outcomes. We
evaluated albuminuria, alone and in combination with estimated glomerular
filtration rate (eGFR), as a predictor of mortality and CV morbidity in 12,944
patients with non-ST-segment elevation acute coronary syndromes. METHODS:
Baseline serum creatinine and urinary dipsticks were obtained, with albuminuria
stratified into no/trace albuminuria, microalbuminuria (>=30 but <300 mg/dL), or
macroalbuminuria (>=300 mg/dL). Kaplan-Meier rates and proportional Cox hazards
models of CV death, overall mortality, CV death or myocardial infarction (MI),
and bleeding were calculated. Incidence of acute kidney injury, identified by
adverse event reporting and creatinine increase (absolute >=0.3 mg/dL or relative
>=50%), was descriptively reported. RESULTS: Both dipstick albuminuria and
creatinine values were available in 9473 patients (73.2%). More patients with
macroalbuminuria, versus no/trace albuminuria, had diabetes (66% vs 27%) or
hypertension (86% vs 68%). Rates for CV death and overall mortality per strata
were 3.1% and 4.8% (no/trace albuminuria); 5.8% and 9.0% (microalbuminuria); and
7.7% and 12.6% (macroalbuminuria) at 2 years of follow-up. Corresponding rates
for CV death or MI were 12.2%, 16.9%, and 23.5%, respectively. Observed acute
kidney injury rates were 0.6%, 1.2%, and 2.9% (n = 79), respectively. Adjusted
HRs for macroalbuminuria on CV mortality were 1.65 (95% CI 1.15-2.37), and after
adjustment with eGFR, 1.37 (95% CI 0.93-2.01). Corresponding HRs for overall
mortality were 1.82 (95% CI 1.37-2.42) and 1.47 (95% CI 1.08-1.98). CONCLUSIONS:
High-risk patients with non-ST-segment elevation acute coronary syndromes and
albuminuria have increased morbidity and increased overall mortality independent
of eGFR.
PMID- 27502847
TI - Rationale and design of a randomized cluster trial to improve guideline-adherence
of secondary preventive drugs prescription after coronary artery bypass grafting
in China: Measurement and Improvement Studies of Surgical Coronary
Revascularization: Secondary Prevention (MISSION-1) Study.
AB - OBJECTIVES: The benefits of secondary preventive drugs after coronary artery
bypass grafting have been thoroughly established. However, the prescription rates
of these drugs are low at discharge in China. We sought to evaluate the
effectiveness of continuous quality improvement with mobile-based interventions
for clinicians on improving the guideline-adherence of secondary preventive drugs
prescription. METHODS AND RESULTS: The quality MISSION-1 study is a cluster
randomized controlled trial. We enrolled 60 hospitals with a bypass surgery
volume of more than 30 a year and randomly assigned them into the intervention
group or the control group in a 1:1 ratio using minimized random grouping. The
intervention group undertakes a series of mobile-based interventions, while the
control group maintains a routine practice pattern. All sites consecutively
register patients who underwent isolated coronary artery bypass grafting and
submit in-hospital data. We require supporting documents regarding prescription
information at discharge to adjudicate the outcome measures. The estimated sample
size of enrolled patients is 9,600. The primary outcome measure is the
prescription rate of statins for eligible patients at discharge. The secondary
outcome measures are beta-blockers, angiotensin-converting enzyme inhibitors or
angiotensin receptor blockers, and optimal medical therapy. MISSION-1 study is
now recruiting patients. CONCLUSIONS: The MISSION-1 study has the potential to
identify the effectiveness of interventions on improving secondary prevention
adherence at discharge after bypass surgery in China and further disseminate
findings to other settings to improve the quality of care.
PMID- 27502848
TI - Impact of baseline mitral regurgitation on short- and long-term outcomes
following transcatheter aortic valve replacement.
AB - BACKGROUND: The prevalence of concomitant significant mitral regurgitation (MR)
in patients with severe aortic stenosis (AS) undergoing transcatheter aortic
valve replacement (TAVR) ranges from 2% to 33%. The impact of significant MR on
post-TAVR outcomes remains controversial. METHODS: The data from a cohort of
patients with symptomatic severe AS undergoing TAVR at out institution were
retrospectively analyzed. The last transthoracic echocardiogram (TTE) before the
index TAVR procedure was selected as the baseline assessment of the degree of MR.
The total study cohort (N = 589) was divided into 2 groups: significant
>=moderate MR (n = 68) versus nonsignificant =moderate MR on mortality at short- and long-term
follow-up periods. RESULTS: Patients with >=moderate MR had a higher mortality
rate versus patients with =moderate
group, 62.5% and 77.7% of patients had improved to 35% and <=45%, >45% and <55%, and >=55%) and as a continuous variable. Secondary
outcomes of interest were 1-year all-cause, cardiovascular, and heart failure
readmissions. RESULTS: The risk of 1-year mortality was 29.0% in patients with EF
<= 35%, compared with 13.0% in patients in the reference group, EF >= 55%
(adjusted hazard ratio [HR] 1.58, 95% CI 1.51-1.66). Relative to patients with EF
>= 55%, patients with EF <= 35% had an increased risk of 1-year all-cause
readmission (adjusted HR 1.20, 95% CI 1.17-1.24), cardiovascular readmission
(adjusted HR 1.36, 95% CI 1.31-1.41), and heart failure readmission (adjusted HR
2.43, 95% CI 2.28-2.60). For patients with EF <= 40%, the hazard of mortality
increased by 26% for every 5% decrease in EF, a finding that remained after risk
adjustment (adjusted HR 1.11, 95% CI 1.09-1.12). CONCLUSIONS: Low EF after MI
remains an important risk factor for postdischarge mortality and hospital
readmission, even after adjustment for patient and hospital characteristics.
PMID- 27502854
TI - Blood pressure control and stroke or bleeding risk in anticoagulated patients
with atrial fibrillation: Results from the ROCKET AF Trial.
AB - BACKGROUND: We conducted a retrospective analysis examining the association
between systolic blood pressure (SBP) or hypertension bracket and stroke risk in
patients with atrial fibrillation (AF). METHODS: The study included 14,256
anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models
were used to compare the risk of adverse outcomes by European Society of
Cardiology hypertension bracket and screening SBP. RESULTS: In total, 90.5% of
patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted
risk of stroke or systemic embolism (SE) increased significantly for every 10-mm
Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There
was a trend toward an increased adjusted risk of stroke or SE in patients with
controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42,
95% CI 1.03-1.95) (P = .06). In contrast, the adjusted risk of major bleeding was
similar between hypertensive brackets and did not vary significantly by screening
SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was
consistent among patients regardless of SBP (P interaction = .69). CONCLUSIONS:
In a trial of anticoagulated patients with AF, increasing screening SBP was
independently associated with stroke and SE, and one-third of patients had
uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban
versus warfarin were consistent across all levels of screening SBP. A single SBP
may be an important factor in reducing the overall risk of stroke and SE in
anticoagulated patients with AF.
PMID- 27502855
TI - Effects of interactive patient smartphone support app on drug adherence and
lifestyle changes in myocardial infarction patients: A randomized study.
AB - BACKGROUND: Patients with myocardial infarction (MI) seldom reach recommended
targets for secondary prevention. This study evaluated a smartphone application
("app") aimed at improving treatment adherence and cardiovascular lifestyle in MI
patients. DESIGN: Multicenter, randomized trial. METHODS: A total of 174
ticagrelor-treated MI patients were randomized to either an interactive patient
support tool (active group) or a simplified tool (control group) in addition to
usual post-MI care. Primary end point was a composite nonadherence score
measuring patient-registered ticagrelor adherence, defined as a combination of
adherence failure events (2 missed doses registered in 7-day cycles) and
treatment gaps (4 consecutive missed doses). Secondary end points included change
in cardiovascular risk factors, quality of life (European Quality of Life-5
Dimensions), and patient device satisfaction (System Usability Scale). RESULTS:
Patient mean age was 58 years, 81% were men, and 21% were current smokers. At 6
months, greater patient-registered drug adherence was achieved in the active vs
the control group (nonadherence score: 16.6 vs 22.8 [P = .025]). Numerically, the
active group was associated with higher degree of smoking cessation, increased
physical activity, and change in quality of life; however, this did not reach
statistical significance. Patient satisfaction was significantly higher in the
active vs the control group (system usability score: 87.3 vs 78.1 [P = .001]).
CONCLUSIONS: In MI patients, use of an interactive patient support tool improved
patient self-reported drug adherence and may be associated with a trend toward
improved cardiovascular lifestyle changes and quality of life. Use of a disease
specific interactive patient support tool may be an appreciated, simple, and
promising complement to standard secondary prevention.
PMID- 27502856
TI - Association of hospital myocardial infarction volume with adherence to American
College of Cardiology/American Heart Association performance measures: Insights
from the National Cardiovascular Data Registry.
AB - BACKGROUND: Adherence to guideline-based therapy improves patient outcomes after
acute myocardial infarction (AMI) and hospital AMI volume is associated with
reperfusion care, but the extent hospital AMI volume is associated with overall
guideline adherence is unclear. METHODS AND RESULTS: We studied 486 hospitals
treating 249,877 AMI patients in ACTION Registry-GWTG from January 1, 2007, to
March 31, 2011. Hospital adherence to each American College of
Cardiology/American Heart Association performance measure was compared between
tertiles defined by hospital AMI volume: low (<=108 cases/y), middle (>=109 and
<=227 cases/y), and high (>=228 cases/y). Multivariable logistic regression,
adjusting for patient and hospital characteristics, was used to examine the
association between annual AMI volume and adherence to each measure. Similar
modeling was used to evaluate the relationship between AMI volume and in-hospital
mortality. Compared with high-volume hospitals, lower-volume hospitals were less
likely to be academically affiliated, or to have cardiac surgery capabilities,
electronic health records, or dedicated tobacco treatment services. Higher-volume
hospitals had greater adherence to each performance measure, except aspirin use
at arrival and reperfusion therapy. The greatest difference was in the rates of
referral to cardiac rehabilitation (59%, 76%, and 83% in low-, middle-, and high
volume hospitals, respectively). After multivariable adjustment, higher AMI
volume (up to 400 AMI patients/y) remained associated with higher-performance
measure adherence. There was no association between AMI volume and in-hospital
mortality after adjusting for patient and hospital characteristics. CONCLUSIONS:
Higher hospital AMI volume was correlated with better adherence to process of
care measures, but not in-hospital mortality.
PMID- 27502857
TI - Effect of ColchiciNe on the InciDence of Atrial Fibrillation in Open Heart
Surgery Patients: END-AF Trial.
AB - BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients
undergoing cardiac surgery and may result in significant morbidity and increased
hospital stay. This study was conducted to determine if colchicine administered
preoperatively to patients undergoing cardiac surgery and continued during
hospitalization is effective in reducing the incidence of postoperative AF.
METHODS: In this multicenter prospective randomized open-label study, consecutive
patients with no history of AF and scheduled to undergo elective cardiac surgery
(n = 360) were randomized to colchicine (n = 179) or no-colchicine (n = 181).
Main exclusion criteria were history of AF or supraventricular arrhythmias or
absence of sinus rhythm at enrolment, and contraindications to colchicine.
Colchicine was orally administered 12 to 24 hours preoperatively and continued
until hospital discharge. The primary efficacy end point was documented AF
lasting more than 5 minutes. Safety end point was colchicine adverse effects.
RESULTS: In-hospital mortality was 3.3%. The primary end point of AF occurred in
63 patients (17.5%): 26 (14.5%) in the colchicine group and 37 (20.5%) in the no
colchicine group (relative risk reduction 29.3% [P = .14]). Diarrhea occurred in
54 patients, 44 (24.6%) on colchicine and 10 (5.5%) on no-colchicine (P < .001).
Diarrhea led to discontinuation of colchicine in 23 (52%) of the 44 patients.
CONCLUSION: Colchicine administered preoperatively to patients undergoing cardiac
surgery and continued until hospital discharge failed to significantly reduce the
incidence of early postoperative AF. Diarrhea was the most common adverse effect
of colchicine leading to its discontinuation in more than half of the patients
with this adverse effect.
PMID- 27502858
TI - Reactive hyperemia is associated with adverse clinical outcomes in heart failure.
AB - INTRODUCTION: Impaired endothelial function, as assessed by brachial artery flow
mediated dilation (FMD), is an established risk factor for cardiovascular events.
FMD is impaired in heart failure (HF) patients, but less is known about hyperemic
brachial artery flow. We investigated the relationship between FMD and hyperemic
flow with adverse clinical outcomes in HF patients. METHODS: Brachial artery FMD
and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian;
mean age (+/- SD) = 56.2 (+/-12.4) years) with HF and reduced left ventricular
ejection fraction (LVEF). Cox proportional hazard models were used to assess the
potential explanatory association of FMD and hyperemic flow with the composite
outcome of death or cardiovascular hospitalization over a median 5-year follow-up
period. RESULTS: Both FMD and hyperemic flow were negatively correlated with age,
but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type
natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was
associated with an increased risk of death or cardiac hospitalization after
controlling for traditional risk factors. CONCLUSION: The association of reduced
hyperemic flow with increased risk of adverse clinical outcomes suggests that
micro-vascular function may be an important prognostic marker in patients with
HF.
PMID- 27502859
TI - Time course, predictors, and prognostic implications of significant mitral
regurgitation after ST-segment elevation myocardial infarction.
AB - BACKGROUND: Ischemic mitral regurgitation (MR) is a known complication of ST
segment elevation myocardial infarction (STEMI) with important prognostic
implications. We evaluated changes over time in ischemic MR after STEMI and the
prevalence and predictors of significant (grade >=2) MR at 12 months.
Furthermore, the prognostic additional value of significant MR at 12-month follow
up over acute MR was assessed. METHODS: STEMI patients (n = 1,599; 77% male; 60
+/- 12 years) treated with primary percutaneous coronary intervention underwent
echocardiography <48 hours of admission (baseline) and at 12 months. Mortality
data were collected during long-term follow-up. RESULTS: At baseline, significant
MR was present in 103 (6%) patients. After 12 months, MR worsened >=1 grade in
321 (20%) patients, remained stable in 963 (60%), and improved >=1 grade in 315
(20%). Significant MR was present in 135 patients at 12 months (8%, P = .01 vs
baseline). Age, left ventricular end-systolic volume, and significant MR at
baseline were independently associated with significant MR at follow-up. During
follow-up (median, 50 months), 121 (8%) patients died (40% of cardiovascular
cause). Significant MR at follow-up was independently associated with all-cause
(hazard ratio, 1.65, 95% CI, 1.02-2.99) and cardiovascular mortality (hazard
ratio, 2.47; 95% CI, 1.24-4.92), also after adjusting for significant MR at
baseline. CONCLUSIONS: The prevalence of significant MR after STEMI increases
over time. Age, baseline left ventricular end-systolic volume, and baseline
significant MR are independently associated with significant MR at follow-up.
Significant MR at 12 months is associated with subsequent all-cause and
cardiovascular mortality and shows additional prognostic value over acute MR.
PMID- 27502860
TI - Left atrial thrombus resolution in atrial fibrillation or flutter: Results of a
prospective study with rivaroxaban (X-TRA) and a retrospective observational
registry providing baseline data (CLOT-AF).
AB - BACKGROUND: Data on left atrial/left atrial appendage (LA/LAA) thrombus
resolution after non-vitamin K antagonist (VKA) oral anticoagulant treatment are
scarce. The primary objective of X-TRA was to explore the use of rivaroxaban for
the resolution of LA/LAA thrombi in patients with nonvalvular atrial fibrillation
(AF) or atrial flutter, with the CLOT-AF registry providing retrospective data
after standard-of-care therapy in this setting. METHODS: X-TRA was a prospective,
single-arm, open-label, multicenter study that investigated rivaroxaban treatment
for 6 weeks for LA/LAA thrombus resolution in patients with nonvalvular AF or
atrial flutter and LA/LAA thrombus confirmed at baseline on a transesophageal
echocardiogram (TEE). CLOT-AF retrospectively collected thrombus-related patient
outcome data after standard-of-care anticoagulant treatment for 3 to 12 weeks in
patients with nonvalvular AF or atrial flutter who had LA/LAA thrombi on TEE
recorded in their medical file. RESULTS: In X-TRA, patients were predominantly
(95.0%) from Eastern European countries. The adjudicated thrombus resolution rate
was 41.5% (22/53 modified intention-to-treat [mITT] patients, 95% CI 28.1%-55.9%)
based on central TEE assessments. Resolved or reduced thrombus was evident in
60.4% (32/53 mITT patients, 95% CI 46.0%-73.6%) of patients. In CLOT-AF, the
reported thrombus resolution rate was 62.5% (60/96 mITT patients, 95% CI 52.0%
72.2%) and appeared better in Western European countries (34/50; 68.0%) than in
Eastern European countries (26/46; 56.5%). CONCLUSION: X-TRA is the first
prospective, multicenter study examining LA/LAA thrombus resolution with a non
VKA oral anticoagulant in VKA-naive patients or in patients with suboptimal VKA
therapy. Rivaroxaban could be a potential option for the treatment of LA/LAA
thrombi.
PMID- 27502861
TI - Evaluating bococizumab, a monoclonal antibody to PCSK9, on lipid levels and
clinical events in broad patient groups with and without prior cardiovascular
events: Rationale and design of the Studies of PCSK9 Inhibition and the Reduction
of vascular Events (SPIRE) Lipid Lowering and SPIRE Cardiovascular Outcomes
Trials.
AB - BACKGROUND: Although statins significantly reduce vascular event rates, residual
cholesterol risk remains high in many patient groups, including those with known
vascular disease as well as in the setting of high-risk primary prevention.
Bococizumab is a humanized monoclonal antibody that inhibits proprotein
convertase subtilisin-kexin type 9 (PCSK9), prolongs the half-life of hepatic low
density lipoprotein (LDL) receptors, and reduces circulating atherogenic
cholesterol levels. DESIGN: The SPIRE program comprises 6 lipid-lowering studies
and 2 cardiovascular outcomes trials, each comparing bococizumab (150 mg
subcutaneously every 2 weeks) to matching placebo. The 6 SPIRE lipid-lowering
studies include 3 parallel 12-month assessments of bococizumab on atherogenic
lipids among statin-treated individuals at high residual risk (SPIRE-HR, SPIRE
LDL, SPIRE-LL), one 12-month study of bococizumab among individuals with familial
hypercholesterolemia (SPIRE-FH), one 6-month study of bococizumab among those
with statin intolerance (SPIRE-SI), and one 3-month study of bococizumab delivery
using an auto-injector device (SPIRE-AI). The SPIRE-1 and SPIRE-2 event-driven
cardiovascular outcome trials will assess the efficacy and safety of bococizumab
in the prevention of incident vascular events in high-risk populations with and
without clinically evident cardiovascular disease who have directly measured
entry LDL cholesterol levels >=70 mg/dL (SPIRE-1, n = 17,000) or >=100 mg/dL
(SPIRE-2, n = 11,000). SUMMARY: The SPIRE trials, inclusive of more than 30,000
participants worldwide, will ascertain the magnitude of reduction in atherogenic
lipids that accrue with bococizumab and determine whether the addition of this
PCSK9 inhibitor to standard treatment significantly reduces cardiovascular
morbidity and mortality in high-risk patients, including those without a history
of clinical cardiovascular events.
PMID- 27502862
TI - Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment
study.
AB - BACKGROUND: Clinical and subclinical (covert) stroke is a cause of cognitive loss
and functional impairment. In the AVERROES trial, we performed serial brain
magnetic resonance imaging (MRI) scans in a subgroup to explore the effect of
apixaban, compared with aspirin, on clinical and covert brain infarction and on
microbleeds in patients with atrial fibrillation. METHODS: We performed brain MRI
(T1, T2, fluid-attenuated inversion recovery, and T2* gradient echo sequences) in
1,180 at baseline and in 931 participants at follow-up. Mean interval from
baseline to follow-up MRI scans was 1.0 year. The primary outcome was a composite
of clinical ischemic stroke and covert embolic pattern infarction (defined as
infarction >1.5 cm, cortical-based infarction, or new multiterritory infarction).
Secondary outcomes included new MRI-detected brain infarcts and microbleeds and
change in white matter hyperintensities. RESULTS: Baseline MRI scans revealed
brain infarct(s) in 26.2% and microbleed(s) in 10.5%. The rate of the primary
outcomes was 2.0% in the apixaban group and 3.3% in the aspirin group (hazard
ratio [HR] 0.55; 0.27-1.14) from baseline to follow-up MRI scan (mean duration of
follow-up: 1 year). In those who completed baseline and follow-up MRI scans, the
rate of new infarction detected on MRI was 2.5% in the apixaban group and 2.2% in
the aspirin group (HR 1.09; 0.47-2.52), but new infarcts were smaller in the
apixaban group (P = .03). There was no difference in proportion with new
microbleeds on follow-up MRI (HR 0.92; 0.53-1.60) between treatment groups.
CONCLUSIONS: Apixaban treatment was associated with a nonsignificant trend toward
reduction in the composite of clinical ischemic stroke and covert embolic-pattern
infarction and did not increase the number of microbleeds in patients with atrial
fibrillation compared with aspirin.
PMID- 27502863
TI - Clinical and echocardiographic characteristics and outcomes in congestive heart
failure at the Hospital of The State University of Haiti.
AB - BACKGROUND: This study aimed to evaluate the clinical and epidemiologic profile
of congestive heart failure at the principal free-care hospital in Haiti.
Cardiovascular disease represents the most prevalent cause of admissions to the
medical service of the University Hospital of the State of Haiti. No previous
study has examined the demographics of congestive heart failure in urban Haiti.
METHODS: Two hundred forty-seven patients presented to the inpatient service
between May 2011 and May 2013. Evaluation included history and physical, CBC,
renal/metabolic profile, serum glucose, anti-HIV antibody, ECG, chest radiograph
and echocardiogram. Treatment included angiotensin converting enzyme inhibitors,
furosemide and spironolactone, carvedilol, digoxin and anticoagulation. RESULTS:
Women (62.4%) outnumbered men; patients were relatively young (mean age 50.1) and
from the lowest socio-economic levels of the population. Nearly all (98.8%)
presented with NYHA III-IV status, with correspondingly high mortality (23.3%).
Echocardiography showed 73% dilated cardiomyopathy; 83% showed moderate to severe
LV systolic dysfunction (mean EF 36.5 +/- 15%) and 17% preserved LV systolic
function. The three principal etiologies were dilated cardiomyopathy (29%)
hypertensive cardiomyopathy (27%) and peripartum cardiomyopathy (20%). Ischemic
cardiomyopathy was rare (3.4%). At 27 months follow-up, 76.7% of the patients
were alive and well. Among those who died, mean survival time was 113 days.
Readmission carried a poor prognosis. CONCLUSIONS: This congestive heart failure
study from Haiti shows an unusually high proportion of young women, primarily due
to peripartum cardiomyopathy. Ischemic cardiomyopathy is rare, as in Africa.
Further study is warranted to address the particular problem of the high
frequency of peripartum cardiomyopathy in this population.
PMID- 27502864
TI - Defining nonvalvular atrial fibrillation: A quest for clarification.
AB - Non-vitamin K oral anticoagulants (NOACs) are currently recommended for patients
with nonvalvular atrial fibrillation since the publication of the 4 major pivotal
trials evaluating the efficacy and safety of factor IIa and factor Xa inhibitors.
The definition of nonvalvular atrial fibrillation is unclear, varying from one
trial to another and even between North American and European guidelines, which
is a source of uncertainties in clinical practice. However, many patients with
atrial fibrillation present signs of valvular involvement, and clarification of
this term is needed to not deny NOACs to patients based on the wrong perception
that they may have valvular atrial fibrillation. The currently unique
contraindications to NOACs are patients with mechanical heart valves and those
with moderate-to-severe mitral stenosis, as stated by the recent 2015 position
paper of the European Heart Rhythm Association. Patients with native heart valve
involvement, regardless of their severity, are suitable for NOAC therapy.
Patients with bioprosthetic heart valves and mitral valve repair may be suitable
for NOACs except for the first 3 and the first 3-6 months postoperatively,
respectively. Patients with transaortic valve implantation or percutaneous
transluminal aortic valvuloplasty are also considered as being eligible for
NOACs, although the bleeding risk has to be carefully considered in this
population often requiring a combination with antiplatelet therapy. Future
studies are warranted to increase the level of evidence of use of NOACs,
particularly in patients with transaortic valve implantation and valvular
surgery, and to determine whether they could be used in the future in the only 2
remaining contraindications.
PMID- 27502865
TI - Very early administration of glucose-insulin-potassium by emergency medical
service for acute coronary syndromes: Biological mechanisms for benefit in the
IMMEDIATE Trial.
AB - AIMS: In the IMMEDIATE Trial, intravenous glucose-insulin-potassium (GIK) was
started as early as possible for patients with suspected acute coronary syndrome
by ambulance paramedics in communities. In the IMMEDIATE Biological Mechanism
Cohort substudy, reported here, we investigated potential modes of GIK action on
specific circulating metabolic components. Specific attention was given to
suppression of circulating oxygen-wasting free fatty acids (FFAs) that had been
posed as part of the early GIK action related to averting cardiac arrest.
METHODS: We analyzed the changes in plasma levels of FFA, glucose, C-peptide, and
the homeostasis model assessment (HOMA) index. RESULTS: With GIK, there was rapid
suppression of FFA levels with estimated levels for GIK and placebo groups after
2 hours of treatment of 480 and 781 MUmol/L (P<.0001), even while patterns of FFA
saturation remained unchanged. There were no significant changes in the HOMA
index in the GIK or placebo groups (HOMA index: placebo 10.93, GIK 12.99; P =
.07), suggesting that GIK infusions were not countered by insulin resistance.
Also, neither placebo nor GIK altered endogenous insulin secretion as reflected
by unchanging C-peptide levels. CONCLUSION: These mechanistic observations
support the potential role of FFA suppression in very early cardioprotection by
GIK. They also suggest that the IMMEDIATE Trial GIK formula is balanced with
respect to its insulin and glucose composition, as it induced no endogenous
insulin secretion.
PMID- 27502866
TI - Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment
elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist
for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial.
AB - BACKGROUND: Antithrombotic therapy plays an important role in the treatment of
non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated
with bleeding risk. Advanced age may modify the relationship between efficacy and
safety. METHODS: Efficacy and safety of vorapaxar (a protease-activated receptor
1 antagonist) was analyzed across ages as a continuous and a categorical variable
in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate
the effect of age, Cox regression models were developed to estimate hazard ratios
(HRs) with the adjustment of other baseline characteristics and randomized
treatment for the primary efficacy composite of cardiovascular death, myocardial
infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent
coronary revascularization, and the primary safety composite of moderate or
severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO)
bleeding. RESULTS: The median age of the population was 64years (25th, 75th
percentiles = 58, 71). Also, 1,791 patients (13.8%) were <=54years of age, 4,968
(38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years,
and 2,206 (17.1%) were 75years or older. Older patients had higher rates of
hypertension, renal insufficiency, and previous stroke and worse Killip class.
The oldest age group (>=75years) had substantially higher 2-year rates of the
composite ischemic end point and moderate or severe GUSTO bleeding compared with
the youngest age group (<=54years). The relationships between treatment
assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For
the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo
in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89
(0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435).
Similar to what was observed for efficacy outcomes, we did not observe any
interaction between vorapaxar and age on bleeding outcomes. For the composite of
moderate or severe bleeding according to the GUSTO classification, the HRs (95%
CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34),
1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value
for interaction = .574). CONCLUSION: Older patients had a greater risk for
ischemic and bleeding events; however, the efficacy and safety of vorapaxar in
NSTE ACS were not significantly influenced by age.
PMID- 27502867
TI - Risky business: Personalizing the approach to percutaneous coronary intervention.
PMID- 27502868
TI - Predicting in-hospital worsening heart failure at time of admission, but do we
really need another heart failure risk model?
PMID- 27502870
TI - Development and validation of a risk model for in-hospital worsening heart
failure from the Acute Decompensated Heart Failure National Registry (ADHERE).
AB - BACKGROUND: A subset of patients hospitalized with acute heart failure
experiences in-hospital worsening heart failure, defined as persistent or
worsening signs or symptoms requiring an escalation of therapy. METHODS: We
analyzed data from the Acute Decompensated Heart Failure National Registry
(ADHERE) linked to Medicare claims to develop and validate a risk model for in
hospital worsening heart failure. Our definition of in-hospital worsening heart
failure included events such as escalation of medical therapy (eg, inotropic
medications) >12hours after admission. We considered candidate risk prediction
variables routinely assessed at admission, including age, medical history,
biomarkers, and renal function. We used logistic regression with robust standard
errors to generate a risk model in a 66% random derivation sample; we validated
the model in the remaining 34%. We evaluated the calibration and discrimination
of the model in both samples. RESULTS: We evaluated 23,696 patients hospitalized
with acute heart failure. Baseline characteristics were well matched in the
derivation and validation samples, and the occurrence of in-hospital worsening
heart failure was similar in both samples (15.4% and 15.6%, respectively). In the
multivariable model, the strongest predictors of in-hospital worsening heart
failure were increased troponin and creatinine. The model was well calibrated and
had good discrimination in the derivation sample (c statistic, 0.74) and
validation sample (c statistic, 0.72). CONCLUSIONS: The ADHERE worsening heart
failure risk model is a clinical tool with good discrimination for use in
patients hospitalized with acute heart failure to identify those at increased
risk for in-hospital worsening heart failure. This tool may be useful to target
treatment strategies for patients at high risk for in-hospital worsening heart
failure.
PMID- 27502871
TI - Asymptomatic severe aortic stenosis: Cardiopulmonary exercise testing in "The
World of AVATAR".
PMID- 27502869
TI - Understanding physician-level barriers to the use of individualized risk
estimates in percutaneous coronary intervention.
AB - BACKGROUND: The foundation of precision medicine is the ability to tailor therapy
based upon the expected risks and benefits of treatment for each individual
patient. In a prior study, we implemented a software platform, ePRISM, to execute
validated risk-stratification models for patients undergoing percutaneous
coronary intervention and found substantial variability in the use of the
personalized estimates to tailor care. A better understanding of physicians'
perspectives about the use of individualized risk-estimates is needed to overcome
barriers to their adoption. METHODS: In a qualitative research study, we
conducted interviews, in-person or by telephone, with 27 physicians at 8 centers
that used ePRISM until thematic saturation occurred. Data were coded using
descriptive content analyses. RESULTS: Three major themes emerged among
physicians who did not use ePRISM to support decision making: (1) "Experience
versus Evidence," physicians' preference to rely upon personal experience and
subjective assessments rather than objective risk estimates; (2) "Omission of
Therapy," the perception that the use of risk models leads to unacceptable
omission of potentially beneficial therapy; and (3) "Unnecessary Information,"
the opinion that information derived from risk models is not needed because
physicians' decision making is already sound and they already know the
information. CONCLUSIONS: Barriers to the use of risk models in clinical practice
include physicians' perceptions that their experience is sufficient, that models
may lead to omission of therapy in patients that may benefit from therapy, and
that they already provide good care. Anticipating and overcoming these barriers
may improve the adoption of precision medicine.
PMID- 27502872
TI - Response: Asymptomatic severe aortic stenosis: Cardiopulmonary exercise testing
in "the world of AVATAR".
PMID- 27502873
TI - To the Editor.
PMID- 27502874
TI - In response to Letter to the Editor.
PMID- 27502875
TI - Greater Attention to Task-Relevant Threat Due to Orbitofrontal Lesion.
AB - Injury to the orbitofrontal cortex (OFC) is a frequent consequence of head injury
and may lead to dysfunctional regulation of emotional and social behavior.
Dysfunctional emotional behavior may partly be related to the role of the OFC in
emotion-attention interaction, as reported previously. In order to better
understand its role in emotion-attention and emotion-cognitive control
interactions, we investigated attention allocation to task-relevant and task
irrelevant threat-related emotional stimuli during a task requiring cognitive
control in patients with lesion to the OFC. We measured the behavioral
performance and event-related potentials (ERP) of 13 patients with OFC lesion and
11 control subjects during a Go/NoGo visual discrimination task. In the task,
line drawings of threatening (spider) and neutral (flower) figures served as
either task-relevant Go or NoGo signals, or as task-irrelevant distractors.
Overall performance did not differ between the groups. In contrast to the control
group performance, the orbitofrontal group performance was improved by relevant
threat signal in comparison with neutral signal. Further, task-relevant threat
signals evoked larger frontocentral N2-P3 amplitude in the orbitofrontal group.
Taken together, behavioral and electrophysiological results suggest that patients
with OFC injury allocated more attentional and cognitive control resources in the
context of task-relevant emotional stimuli. This study provides new evidence for
the role of the OFC in emotion-attention and emotion-cognitive control
interactions. Further, the OFC seems to contribute to the balance between
voluntary and involuntary attention networks in context of emotional stimuli.
Better understanding of alterations in emotion-attention interaction offers
insight into affective dysfunction due to OFC lesion.
PMID- 27502876
TI - Factors affecting orocutaneous fistula formation following head and neck
reconstructive surgery.
AB - This paper explores factors associated with the formation of orocutaneous fistula
following head and neck reconstructive surgery, and considers ways this
complication may be reduced. We retrospectively analysed the medical notes of 102
patients who had reconstructive surgery at the study centre over a 17-month
period. Information included patient comorbidities, previous oncological
treatment, duration of hospital stay, complications, incidence of fistulas, and
the day on which oral intake started. Patients who had previously had
chemoradiotherapy were significantly more likely to develop a fistula than those
who had not (p=0.008). Associations between other variables were not significant.
Our analysis identifies a considerable number of patients who require head and
neck reconstructive surgery as a result of new primary or recurrent tumours
within previously irradiated fields. It also demonstrates the impact of previous
chemoradiotherapy on many elements of recovery and rehabilitation, including but
not limited to fistula formation. Treatment for this group of patients requires
careful consideration and planning, as their recovery trajectory may be different
from those patients who undergo surgery as a primary intervention. We suggest
ways to reduce the incidence of fistulas, which include the avoidance of oral
intake before the eighth postoperative day.
PMID- 27502877
TI - Physiological marker and surgical ligation of patent ductus arteriosus in
neonates.
AB - BACKGROUND: In preterm infants, immediate complications of surgical closure of a
patent ductus arteriosus (PDA) are often serious and due to haemorrhage or
ligation of incorrect structures. The aim of this study was to measure blood
pressure (BP) changes during ligation and hence introduce a novel physiological
marker to alert surgeons to the ligation of incorrect structures. MATERIALS AND
METHODS: This study included 146 preterm babies (<=35 weeks of gestation) who
underwent surgical PDA closure of a left-to-right unidirectional PDA between June
2006 and December 2015. The median weight was 920 g (range, from 520 to 2200 g).
In all cases, the PDA was test cross-clamped, and the lower limb or umbilical
artery BP was recorded before ligation. RESULTS: Based on preoperative
echocardiography, the PDA diameter range was 2-4 mm in 135 cases and 5-6 mm in 11
cases. During test clamping of the PDA, a 20-60% rise in mean BP was recorded.
The lower figure was observed with smaller PDAs. CONCLUSION: It is estimated that
the mean BP should rise by 10% for every mm of PDA diameter during test clamping
and ligation of the PDA, irrespective of weight or age. The absence of this
expected rise in mean BP indicates that an incorrect structure might have been
clamped.
PMID- 27502878
TI - Management of oesophageal atresia in a developing country: Is primary repair
forbidden?
AB - BACKGROUND: The aim of the study was to evaluate the outcomes of initial surgical
procedures for oesophageal atresia at our institution. Primary repair of
oesophageal atresia at our centre was perceived to be associated with a high
mortality rate. In view of this, almost all patients seen since January 2014 were
offered initial surgery for staged repair. MATERIALS AND METHODS: A retrospective
review of records of infants with oesophageal atresia seen at the centre from
January 2007 to December 2014 was used in this study. RESULTS: Eighty-five cases
of oesophageal atresia were seen over the study period. Of these, 74 (87.1) had
surgery performed. Surgical outcome was, however, indicated in 67 of the 74, with
overall survival rate of 40.3%. Among the 67 patients, early primary repair was
performed in 24 (35.8%) with a survival rate of 45.8% (11 patients). Totally, 12
(17.9%) of the 67 had initial procedure for delayed primary repair, with a
survival rate of 16.7% (2 patients). The remaining 31 (46.3%) patients had
initial surgery for staged repair, with survival rate of 45.2% (14 patients).
There was no association between the type of surgery and the surgical outcome
(chi2 = 3.396, df = 2, P = 0.183). CONCLUSION: The overall surgical survival rate
of 40.3% for oesophageal atresia at our institution is low. This study did not
show any difference in the survival rate of 45.8% and 45.2% associated with
primary repair and staged repair respectively.
PMID- 27502879
TI - Clinical spectrum of neonates presenting with pneumoperitoneum: A retrospective
study.
AB - BACKGROUND: Neonatal pneumoperitoneum is attributed, in most of the reported
cases, to necrotising enterocolitis (NEC). There are also other causes leading to
free intraperitoneal air. The aim of this study is to describe the clinical
spectrum, causes, management and outcome of neonates admitted with
pneumoperitoneum in the paediatric surgery unit of a university hospital.
SUBJECTS AND METHODS: This retrospective study included neonates having
radiographic evidences of pneumoperitoneum from 2012 to the end of 2014.
Patients' files were analysed regarding age at admission, birth weight, history,
clinical picture, management, operative findings and subsequent outcome. RESULTS:
Fifty-six out of 379 neonates (14.7%) were found to have pneumoperitoneum during
the study period. There were 35 males (62.5%) and 21 females (37.5%). Cases
diagnosed as NEC represented 27 neonates (48.2%). There were 29 cases (51.8%)
with causes not related to NEC. Non-NEC causes were spontaneous intestinal
perforation (8.9%), ano-rectal malformations (7.1%), Hirschsprung's disease
(14.2%), ileal atresia (3.5%), incarcerated inguinal hernia (1.7%), gastric
perforation (1.7%) and meconium ileus (1.7%). In seven patients (12.5%), those
who were managed conservatively (8.9%) or whose laparotomy was negative (3.6%),
no cause of pneumoperitoneum could be reached. Overall mortality was 25%, 78.5%
of which was NEC-related. CONCLUSIONS: Neonatal pneumoperitoneum is an alerting
finding for paediatric surgeons. Most cases imply serious causes with a
significant morbidity and mortality, NEC being the most common cause. On the
other hand, pneumoperitoneum is not an absolute indication for surgery. Careful
assessment and tailored management can limit the morbidity of unnecessary
laparotomies.
PMID- 27502880
TI - Lower limbs deformities in patients with McCune-Albright syndrome: Tomography and
treatment.
AB - BACKGROUND: The skeletal changes in McCune-Albright disease are usually severe
because of the polyostotic form of the disease. Trendelenberg gait and limited
mobility are the most common presenting features. The constellation of Cafe-au
lait spots and polyostotic bone involvement is commonly referred to as McCune
Albright's syndrome (MAS). MATERIALS AND METHODS: One boy and 4 girls (7-16
years) were sought in our departments from 1998 to 2012. Limb length discrepancy
was the main clinical presentation. Repetitive micro-fractures caused the
development of 'Shepherd crook' deformity with pain were the main burden.
RESULTS: Because of the repetitive micro-fractures and the significant deformity
that distorted the integrity of the long bones which were associated with pain.
We referred to re-alignment valgus osteotomy with internal fixation to preserve
proper alignment. Moreover, guided growth technique with 8-plates was performed
in 1 case. CONCLUSION: Tendency to progressive unilateral lower limb deformity in
patients with MAS is usually associated with thinning and expansion of the cortex
and distortion of the normal lower limb integrity secondary to repetitive micro
fractures. The latter is a situation which warrants surgical treatment to re
align the deformity and to preserve function. Prophylactic intramedullary nailing
via the application of locking nails to ensure stabilisation of the femoral neck
was found to be effective. However, nevertheless, the mosaic nature of MAS means
any cell, tissue and organ in any site of the body could be affected to varying
degrees. The clinical manifestations are a diversity of the disorder ranging from
mild clinical signs to severe life-threatening disease.
PMID- 27502881
TI - Digital camera image analysis of faeces in detection of cholestatic jaundice in
infants.
AB - BACKGROUND: Stool colour assessment is a screening method for biliary tract
obstruction in infants. This study is aimed to be a proof of concept work of
digital photograph image analysis of stool colour compared to colour grading by a
colour card, and the stool bilirubin level test. MATERIALS AND METHODS: The total
bilirubin (TB) level contents in stool samples from 17 infants aged less than 1
year, seven with confirmed cholestatic jaundice and ten healthy subjects was
measured, and outcome correlated with the physical colour of the stool. RESULTS:
The seven infants with cholestasis included 6 cases of biliary atresia and 1 case
of pancreatic mass. All pre-operative stool samples in these cases were indicated
as grade 1 on the stool card (stool colour in healthy infants ranges from 4 to
6). The average stool TB in the pale stool group was 43.07 MUg/g compared to
101.78 MUg/g in the non-pale stool group. Of the 3 colour channels assessed in
the digital photographs, the blue and green light were best able to discriminate
accurately between the pre-operative stool samples from infants with cholestasis
and the samples from the healthy controls. With red, green, and blue (RGB) image
analysis using wave level as the ANN input, the system predicts the stool TB with
a relationship coefficient of 0.96, compared to 0.61 when stool colour card
grading was used. CONCLUSION: Input from digital camera images of stool had a
higher predictive capability compared to the standard stool colour card,
indicating using digital photographs may be a useful tool for detection of
cholestasis in infants.
PMID- 27502882
TI - Association between plasma kisspeptin levels and adolescent gynecomastia.
AB - BACKGROUND: Gynecomastia is defined as benign proliferation of male breast
glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG)
remains unclear. Kisspeptin is a polypeptide that plays an important role in the
regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we
investigated whether there is a relationship between kisspeptin and AG. MATERIALS
AND METHODS: This study included 40 males between 9 and 18 years of age diagnosed
with gynecomastia. The control group consisted of 30 young healthy males in the
same age range. The participants were evaluated with respect to anthropometric
measurements (age, height, body weight, body mass index, breast and pubic stages
and testicular volume). The levels of kisspeptin, follicle-stimulating hormone,
luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were
measured in both groups. RESULTS: The mean age was 13.8 years. There were no
differences between the groups in terms of anthropometric parameters, plasma
gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin
(0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were
significantly higher in the AG group than in the control group (P < 0.001).
CONCLUSION: Kisspeptin levels are an important factor in AG.
PMID- 27502883
TI - The value of using loupe magnification and methylene blue dye in intra-operative
identification of thyroglossal duct tract.
AB - BACKGROUND: This was a comparative randomised study to find out the value of
using loupe magnification and methylene blue dye in identification of the
thyroglossal duct and to compare between them. PATIENTS AND METHODS: Twenty-two
patients who presented with infrahyoid thyroglossal duct cyst were subjected to
excision of the cyst with two methods for identification of thyroglossal duct
track during the operation. Data were anlysed for identification of multiple
tracts, the tract relation to the hyoid bone, incidence of complications and
operative time. RESULTS: We found that multiple tracts were present in 9.1% of
the patients in Group I and 36.3% in Group II, with no statistically significant
difference between the two groups. The incidence of complications was 27.2% in
Group I and 9.1% in Group II, with no statistically significant difference
between both groups. However, the incidence of identification of the tract, and
its relation to the hyoid bone was higher in Group II (90.9%) than in Group I
(45.5%) , with a statistically significant difference between both groups. Also
the incidence of identification of the extension level of the tract above the
hyoid bone and up to the tongue base was significantly higher in Group II (72.8%)
as compared to Group I (9.1%). The operative time was significantly shorter in
Group II (54.35 min) and was 76.55 min in Group I, (P = 0.0001). CONCLUSION:
Intra-operative identification of the thyroglossal tract is an essential step in
the removal of the thyroglossal duct cyst. Both loupe magnification and methylene
blue dye help in the tract identification, however, the usage of surgical loupes
enhances better and safe results.
PMID- 27502884
TI - Mixed gonadal dysgenesis in Yaounde: A preliminary experience about three cases.
AB - Mixed gonadal dysgenesis is characterised by unilateral chromosomal abnormality,
which is probably the result of anaphase lag during mitosis. The 45, XO/46, XY
karyotype is the most common form of mosaicism involving the Y chromosome. It is
a rare clinical entity with a worldwide incidence of 1.5/10,000 live births. Its
epidemiology in Sub-Saharan Africa is not known. This study reports experience in
the management of 3 cases at the Yaounde Gynecologic-Obstetric and Paediatric
Hospital. From November 2009 to November 2014, 3 cases were successfully managed
at our institution. RESULTS: All patients presented with asymmetrical gonadal
differentiation. On one side of the body, a poorly-developed testicular gonad and
on the other side a gonadal streak. A persistent Momicronllerian remnant was
equally found in the 3 cases. Management of mixed gonadal dysgenesis should be
done in tertiary health care centres. A multidisciplinary team approach is
recommended.
PMID- 27502885
TI - Laparoscopic management of an axially torsed gangrenous Meckel's diverticulum in
a child.
AB - Meckel's diverticulum (MD) is the most common congenital anomaly of the
gastrointestinal tract. Most often is asymptomatic but it may give a number of
complications including gastrointestinal bleeding, obstruction and inflammation.
Axial torsion and gangrene of MD are exceptional. The correct diagnosis of MD
could only be made during surgery. Early surgery is important to reduce
morbidity, especially perforation. Laparoscopy aided in the diagnosis and
adequate treatment. We herein describe the case of a 4-year-old boy with axial
torsion of MD. Clinical and radiographic finding suggest a segmental volvulus.
Laparoscopy contributes to diagnosis and treatment of torted MD.
PMID- 27502886
TI - A case report of Cowper's syringocele in an 18-months old infant at the Yaounde
Gynaeco-Obstetric and Pediatric Hospital.
AB - Syringocele or dilatation of the duct of the bulbo-urethral (Cowper's) gland is
usually of congenital origin but can be acquired. It is a very rare deformity,
<10 cases have been reported in literature. The main objective is to describe an
additional case of syringocele of Cowper's glands and review the literature. An
18-month-old infant presented with a history of acute urinary retention 3 days
after birth and a cystostomy was done. Voiding cystourethrogram was normal and
cystourethroscopy showed a syringocele. Endoscopic incision was performed in our
patient with satisfactory results. No complications were noted. Syringocele or
cystic dilatation of Cowper's gland duct usually has a congenital aetiology.
Diagnosis is confirmed by endoscopy. Treatment is by marsupialisation in the
urethra by endoscopy. Syringocele is a rare pathology usually congenital. It
should be suspected in all case of lower urinary tract obstruction in children.
PMID- 27502887
TI - Penetrating chest wound of the foetus.
AB - Traumas of the foetus caused by stabbings are rare but actually life-threatening
for both the foetus and the mother. We report a case of penetrating chest wound
on a baby taken from the obstetrics unit to the paediatric surgical department.
His mother was assaulted by his father, a mentally sick person with no
appropriate follow-up. The foetus did not show any sign of vital distress.
Surgical exploration of the wound has revealed a section of the 10 th rib, a
laceration of the pleura and a tearing of the diaphragm. A phrenorraphy and a
pleural drainage were performed. The new-born and its mother were released from
hospital after 5 days and the clinical control and X-ray checks 6 months later
showed nothing abnormal. We insisted a medical, psychiatric follow-up be
initiated for the father. As regards pregnant women with penetrating wounds, the
mortality rate of the foetus is 80%. The odds are good for our newborn due to the
mild injuries and good professional collaboration of the medical staff.
Penetrating transuterine wounds of the foetus can be very serious. The health
care needed should include many fields due to the mother and the foetus' lesions
extreme polymorphism. In our case, it could have prevented by a good psychiatric
followed up of the offender.
PMID- 27502888
TI - Visceral basidiobolomycosis.
PMID- 27502889
TI - Traumatic chest injury in children.
PMID- 27502890
TI - Post-traumatic growth in breast cancer: how and when do distress and stress
contribute?
AB - OBJECTIVE: While several theoretical models provide explanation for the genesis
and development of post-traumatic growth (PTG) in the aftermath of stressful
events, empirical evidence regarding the predictors and consequences of PTG in
breast cancer patients in active treatment and early survivorship is
inconclusive. This study, therefore, examines the role of distress and stress as
predictors and outcomes of PTG in women with breast cancer over an 18-month
period. METHODS: These effects are tested in two structural equation models that
track pathways of PTG in a sample of 253 recently diagnosed women. Questionnaires
were completed at diagnosis and at 4 follow-up time points assessing cancer
specific stress (Impact of Events Scale), global stress (Perceived Stress Scale),
and depression and anxiety (Hospital Anxiety and Depression Scale). Post
traumatic growth (Silver Lining Questionnaire) was assessed at follow-up time
points. RESULTS: Cancer-specific stress was related to higher PTG concurrently
and longitudinally. Anxiety was related concurrently to higher PTG, but overall
general distress had minimal impact on PTG. Global stress was inversely related
to PTG. Positive growth at 6 months was associated with subsequent reduction in
stress. CONCLUSIONS: This study showing that early stage higher cancer-specific
stress and anxiety were related to positive growth supports the idea that
struggle with a challenging illness may be instrumental in facilitating PTG, and
findings show positive implications of PTG for subsequent adjustment.
PMID- 27502892
TI - Difference between SB4 and reference etanercept in the hepatobiliary disorders
not considered to be caused by SB4: response to letter by Scheinberg and Azevedo.
PMID- 27502891
TI - Risk of lymphoma in patients exposed to antitumour necrosis factor therapy:
results from the British Society for Rheumatology Biologics Register for
Rheumatoid Arthritis.
AB - OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of
lymphoma compared with the general population. There are concerns that tumour
necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the
excess risk of lymphoma in RA is related to the cumulative burden of
inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the
burden of inflammation. The aim of this study was to compare the risk of lymphoma
in subjects with RA treated with TNFi with those treated with non-biological
therapy. METHODS: Subjects diagnosed by a rheumatologist with RA enrolled in the
British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a
prospective cohort study, were followed until first lymphoma, death or until 30
November 2013. Rates of lymphoma in the TNFi and non-biological-treated cohorts
were compared using Cox regression. RESULTS: 11 931 TNFi-treated patients were
compared with 3367 biological-naive patients. 84 lymphomas (88 (95% CI 70 to 109)
per 100 000 person-years) were reported in the TNFi cohort and 30 lymphomas (154
(95% CI 104 to 220)) in the biological-naive cohort. After adjusting for
differences in baseline characteristics, there was no difference in the risk of
lymphoma for the TNFi versus the biological-naive group: HR 1.00 (95% CI 0.56 to
1.80). No risk differences were observed for individual TNFi. CONCLUSIONS: In
medium-term follow-up, there is no evidence that tumour necrosis factor
inhibition influences the risk of lymphoma over the background risk in subjects
with RA.
PMID- 27502893
TI - Caenorhabditis elegans chronically exposed to a Mn/Zn ethylene-bis
dithiocarbamate fungicide show mitochondrial Complex I inhibition and increased
reactive oxygen species.
AB - Reports have linked human exposure to Mn/Zn ethylene-bis-dithiocarbamate (Mn/Zn
EBDC) fungicides with multiple pathologies, from dermatitis to central nervous
system dysfunction. Although members of this family of agrochemicals have been
available for over 50 years, their mechanism of toxicity in humans is still
unclear. Since mitochondrial inhibition and oxidative stress are implicated in a
wide variety of diseases, we hypothesized that Caenorhabditis elegans (C.
elegans) exposed to a commercially-available formulation of an Mn/Zn-EBDC
containing fungicide (Manzate; MZ) would also show these endpoints. Thus, worms
were treated chronically (24h) with various MZ concentrations and assayed for
reduced mitochondrial function and increased levels of reactive oxygen species
(ROS). Oxygen consumption studies suggested Complex I inhibition in all treatment
groups compared to controls (**p<0.01). In order to verify these findings, assays
specific for Complex II or Complex IV activity were also completed. Data analysis
from these studies indicated that neither complex was adversely affected by MZ
treatment. Additional data from ATP assays indicated a statistically significant
decrease (***p<0.001) in ATP levels in all treatment groups when compared to
control worms. Further studies were completed to determine if exposure of C.
elegans to MZ also resulted in increased ROS concentrations. Studies demonstrated
that hydrogen peroxide, but not superoxide or hydroxyl radical, levels were
statistically significantly increased (*p<0.05). Since hydrogen peroxide is known
to up-regulate glutathione-S-transferase (GST), we used a GST:green fluorescent
protein transgenic worm strain to test this hypothesis. Results from these
studies indicated a statistically significant increase (***p<0.001) in green
pixel number following MZ exposure. Taken together, these data indicate that C.
elegans treated with MZ concentrations to which humans are exposed show
mitochondrial Complex I inhibition with concomitant hydrogen peroxide production.
Since these mechanisms are associated with numerous human diseases, we suggest
further studies to determine if MZ exposure induces similar toxic mechanisms in
mammals.
PMID- 27502894
TI - Primary syphilis: An uncommon manifestation in the oral cavity.
PMID- 27502895
TI - Fracture resistance of dental nickel-titanium rotary instruments with novel
surface treatment: Thin film metallic glass coating.
AB - BACKGROUND/PURPOSE: Dental nickel-titanium (NiTi) rotary instruments are widely
used in endodontic therapy because they are efficient with a higher success rate.
However, an unpredictable fracture of instruments may happen due to the surface
characteristics of imperfection (or irregularity). This study assessed whether a
novel surface treatment could increase fatigue fracture resistance of dental NiTi
rotary instruments. METHODS: A 200- or 500-nm thick Ti-zirconium-boron (Ti-Zr-B)
thin film metallic glass was deposited on ProTaper Universal F2 files using a
physical vapor deposition process. The characteristics of coating were analyzed
by scanning electron microscopy, transmission electron microscopy, and X-ray
diffractometry. In cyclic fatigue tests, the files were performed in a simulated
root canal (radius=5 mm, angulation=60 degrees ) under a rotating speed of
300rpm. The fatigue fractured cross sections of the files were analyzed with
their fractographic performances through scanning electron microscopy images.
RESULTS: The amorphous structure of the Ti-Zr-B coating was confirmed by
transmission electron microscopy and X-ray diffractometry. The surface of treated
files presented smooth morphologies without grinding irregularity. For the 200-
and 500-nm surface treatment groups, the coated files exhibited higher resistance
of cyclic fatigue than untreated files. In fractographic analysis, treated files
showed significantly larger crack-initiation zone; however, no significant
differences in the areas of fatigue propagation and catastrophic fracture were
found compared to untreated files. CONCLUSION: The novel surface treatment of Ti
Zr-B thin film metallic glass on dental NiTi rotary files can effectively improve
the fatigue fracture resistance by offering a smooth coated surface with
amorphous microstructure.
PMID- 27502896
TI - Novel approaches to characterize age-related remodelling of the dermal-epidermal
junction in 2D, 3D and in vivo.
AB - BACKGROUND/PURPOSE: The dermal-epidermal junction (DEJ) forms epidermal
protrusions down into the dermis (rete ridges) and dermal projections up into the
epidermis (dermal papillae). Usually visualized in two-dimensions (2D), our
knowledge of how the DEJ changes with ageing is limited. We aimed to characterize
how this structure exists in 3D and changes with age. METHODS: Photoprotected and
photoexposed skin were imaged using reflectance confocal microscopy (RCM) in
young and aged individuals. Biopsies of the imaged areas were processed for
histological sectioning and for imaging using micro-computed X-ray tomography
(microCT). RESULTS: Images obtained from RCM and microCT were used to 3D
reconstruct the DEJ. DEJ heights obtained from microCT images showed strong
correlation with histology-measured heights. We proposed a novel definition of
rete ridges (RRm ) and dermal papillae (DPm ), which allowed easier automated
measurement of reduced DPm and RRm volumes in aged skin from microCT
reconstructions. An algorithm to map DPm connectivity showed reduced lengths of
DPm branches with age. CONCLUSION: Three-dimensional images illustrated the
complex topography of the DEJ and highlighted the distinct morphology of dermal
papillae compared with rete ridges, which is not evident when evaluating 2D
sections. Ex vivo imaging was more successful in differentiating DEJ architecture
with respect to age.
PMID- 27502897
TI - Inhibition of Autophagy Enhances Curcumin United light irradiation-induced
Oxidative Stress and Tumor Growth Suppression in Human Melanoma Cells.
AB - Malignant melanoma is the most aggressive form of skin carcinoma, which possesses
fast propagating and highly invasive characteristics. Curcumin is a natural
phenol compound that has various biological activities, such as anti
proliferative and apoptosis-accelerating impacts on tumor cells. Unfortunately,
the therapeutical activities of Cur are severely hindered due to its extremely
low bioavailability. In this study, a cooperative therapy of low concentration
Cur combined with red united blue light irradiation was performed to inspect the
synergistic effects on the apoptosis, proliferation and autophagy in human
melanoma A375 cell. The results showed that red united blue light irradiation
efficaciously synergized with Cur to trigger oxidative stress-mediated cell
death, induce apoptosis and inhibit cell proliferation. Meanwhile, Western
blotting revealed that combined disposure induced the formation of
autophagosomes. Conversely, inhibition of the autophagy enhanced apoptosis,
obstructed cell cycle arrest and induced reversible proliferation arrest to
senescence. These findings suggest that Cur combined with red united blue light
irradiation could generate photochemo-preventive effects via enhancing apoptosis
and triggering autophagy, and pharmacological inhibition of autophagy convert
reversible arrested cells to senescence, therefore reducing the possibility that
damaged cells might escape programmed death.
PMID- 27502898
TI - Boron exposure through drinking water during pregnancy and birth size.
AB - BACKGROUND: Boron is a metalloid found at highly varying concentrations in soil
and water. Experimental data indicate that boron is a developmental toxicant, but
the few human toxicity data available concern mostly male reproduction.
OBJECTIVES: To evaluate potential effects of boron exposure through drinking
water on pregnancy outcomes. METHODS: In a mother-child cohort in northern
Argentina (n=194), 1-3 samples of serum, whole blood and urine were collected per
woman during pregnancy and analyzed for boron and other elements to which
exposure occurred, using inductively coupled plasma mass spectrometry. Infant
weight, length and head circumference were measured at birth. RESULTS: Drinking
water boron ranged 377-10,929MUg/L. The serum boron concentrations during
pregnancy ranged 0.73-605MUg/L (median 133MUg/L) and correlated strongly with
whole-blood and urinary boron, and, to a lesser extent, with water boron. In
multivariable-adjusted linear spline regression analysis (non-linear
association), we found that serum boron concentrations above 80MUg/L were
inversely associated with birth length (B-0.69cm, 95% CI -1.4; -0.024, p=0.043,
per 100MUg/L increase in serum boron). The impact of boron appeared stronger when
we restricted the exposure to the third trimester, when the serum boron
concentrations were the highest (0.73-447MUg/L). An increase in serum boron of
100MUg/L in the third trimester corresponded to 0.9cm shorter and 120g lighter
newborns (p=0.001 and 0.021, respectively). CONCLUSIONS: Considering that
elevated boron concentrations in drinking water are common in many areas of the
world, although more screening is warranted, our novel findings warrant
additional research on early-life exposure in other populations.
PMID- 27502899
TI - Mechanisms of arsenic disruption on gonadal, adrenal and thyroid endocrine
systems in humans: A review.
AB - Due to its toxicity as a carcinogen and wide distribution in the environment,
arsenic (As) exposure in humans is of public concern globally. Many studies have
manifested that As exposure induces cancers besides pathological effects in
humans. Animal studies showed that chronic As exposure induces serious
neurological effects. Based on recent studies, researchers proposed that As,
including arsenate (AsV) and arsenite (AsIII), is also an endocrine disruptor.
This review discusses the mechanisms of As toxicity on three endocrine systems
including gonadal, adrenal and thyroid endocrine systems. Arsenic methylation and
oxidative stress are responsible for As-induced disorders of endocrine systems,
however, strong binding of AsIII to thiols also play an important role. Some
studies showed AsV toxicity on endocrine systems, but mechanistic investigation
is lacking. Research is needed to look into their toxicity mechanisms to help
cure the illnesses caused by As-induced endocrine system disorders.
PMID- 27502901
TI - The Longest Wait: Examining the Impact of Utah's 72-Hour Waiting Period for
Abortion.
AB - PURPOSE: To assess the impact of Utah's 2012 law increasing the mandatory
abortion waiting period from 24 to 72 hours. METHODS: This paper includes two
assessments of this change: (1) Comparison of the proportion of women returning
for an abortion after counseling before and after the introduction of the 72-hour
law and (2) self-reported wait times between abortion and procedure, distance
traveled, financial expenditures, and perceived impact of the law in a subset of
women who were surveyed. MAIN FINDINGS: Aggregate counseling and procedural data
were available at three Utah clinics; 2,793 of 3,618 women (77%) returned for
abortion procedures under the 72-hour law, compared with 2,513 of 3,130 (80%) in
the previous year (p < .05). Among 307 women surveyed, 63% reported more than 7
days between signing the consent form and their procedure, and women frequently
had to travel further to get their procedure than they did for the counseling.
Close to two-thirds (62%) reported the 72-hour wait affected them negatively in
some way, including the lost wages of needing to take extra time off work (47%),
increased transportation cost (30%), lost wages by family or friend(s) (27%), and
having to disclose their abortion to someone they would not had told without the
waiting period (33%). CONCLUSION: Utah's extended waiting period showed a small
reduction in the proportion of counseled women who returned for their abortion
procedure statewide. Women who had abortions after the law was enacted reported
several burdensome aspects of the law.
PMID- 27502900
TI - No evidence for spectral jamming avoidance in echolocation behavior of foraging
pipistrelle bats.
AB - Frequency shifts in signals of bats flying near conspecifics have been
interpreted as a spectral jamming avoidance response (JAR). However, several
prerequisites supporting a JAR hypothesis have not been controlled for in
previous studies. We recorded flight and echolocation behavior of foraging
Pipistrellus pipistrellus while flying alone and with a conspecific and tested
whether frequency changes were due to a spectral JAR with an increased frequency
difference, or whether changes could be explained by other reactions. P.
pipistrellus reacted to conspecifics with a reduction of sound duration and often
also pulse interval, accompanied by an increase in terminal frequency. This
reaction is typical of behavioral situations where targets of interest have
captured the bat's attention and initiated a more detailed exploration. All
observed frequency changes were predicted by the attention reaction alone, and do
not support the JAR hypothesis of increased frequency separation. Reaction
distances of 1-11 m suggest that the attention response may be elicited either by
detection of the conspecific by short range active echolocation or by long range
passive acoustic detection of echolocation calls.
PMID- 27502902
TI - Chromatographic method for clobetasol propionate determination in hair follicles
and in different skin layers.
AB - Clobetasol propionate (CLO) is a potent steroid used for the treatment of several
dermatological diseases. Recent studies suggest its additional use in alopecia
topical treatment, generating a demand for novel formulations with specific
delivery into hair follicles. Hence, a selective analytical method for drug
quantification in follicular structures and skin layers is required. For this, a
simple HPLC-UV method was developed. Quantification was performed using a RP-C18
column (4.6 mm * 15 cm, 5 MUm), with a mixture of methanol-acetonitrile-water
(50:15:35 v/v) as mobile phase, a flow rate of 1.2 mL/min, oven temperature of 30
degrees C, injection volume of 50 MUL and detection at 240 nm. The optimized
conditions enabled a 12 min running with CLO elution at 10.1 min and resolution
of 2.424 from skin matrix interferences. Validation was performed in accordance
with International Conference on Harmonization guidelines and fulfilled the
criteria of selectivity, linearity (0.5-15.0 MUg/mL), robustness, precision,
accuracy and limits of detection and quantification (0.02 and 0.07 MUg/mL,
respectively). The validated method was successfully applied for CLO
quantification following in vitro skin permeation experiments and differential
tape-stripping for hair follicle deposition determination, demonstrating its
suitability.
PMID- 27502903
TI - The hills and valleys of calcium signaling.
PMID- 27502904
TI - Recent advances in the research for the homolog of breast cancer associated gene
AtROW1 in higher plants.
AB - BARD1 (BRCA1 associated RING domain protein 1), as an important animal tumor
suppressor gene associated with many kinds of cancers, has been intensively
studied for decades. Surprisingly, homolog of BARD1 was found in plants and it
was renamed AtROW1 (repressor of Wuschel-1) according to its extremely important
function with regard to plant stem cell homeostasis. Although great advances have
been made in human BARD1, the function of this animal tumor-suppressor like gene
in plant is not well studied and need to be further elucidated. Here, we review
and summarize past and present work regarding this protein. Apart from its
previously proposed role in DNA repair, recently it is found essential for shoot
and root stem cell development and differentiation in plants. The study of AtROW1
in plant may provide an ideal model for further elucidating the functional
mechanism of BARD1 in mammals.
PMID- 27502905
TI - Prevalence and phylogenetic characterization of canine coronavirus from diseased
pet dogs in Beijing, China.
PMID- 27502906
TI - Heart Failure With Preserved Ejection Fraction: A Kidney Disorder?
PMID- 27502907
TI - Parsing Atherosclerosis: The Unnatural History of Peripheral Artery Disease.
PMID- 27502908
TI - Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis
of Population-Based Studies From 90 Countries.
AB - BACKGROUND: Hypertension is the leading preventable cause of premature death
worldwide. We examined global disparities of hypertension prevalence, awareness,
treatment, and control in 2010 and compared secular changes from 2000 to 2010.
METHODS: We searched MEDLINE from 1995 through 2014 and supplemented with manual
searches of retrieved article references. We included 135 population-based
studies of 968 419 adults from 90 countries. Sex- and age-specific hypertension
prevalences from each country were applied to population data to calculate
regional and global numbers of hypertensive adults. Proportions of awareness,
treatment, and control from each country were applied to hypertensive populations
to obtain regional and global estimates. RESULTS: In 2010, 31.1% (95% confidence
interval, 30.0%-32.2%) of the world's adults had hypertension; 28.5% (27.3%
29.7%) in high-income countries and 31.5% (30.2%-32.9%) in low- and middle-income
countries. An estimated 1.39 (1.34-1.44) billion people had hypertension in 2010:
349 (337-361) million in high-income countries and 1.04 (0.99-1.09) billion in
low- and middle-income countries. From 2000 to 2010, the age-standardized
prevalence of hypertension decreased by 2.6% in high-income countries, but
increased by 7.7% in low- and middle-income countries. During the same period,
the proportions of awareness (58.2% versus 67.0%), treatment (44.5% versus
55.6%), and control (17.9% versus 28.4%) increased substantially in high-income
countries, whereas awareness (32.3% versus 37.9%) and treatment (24.9% versus
29.0%) increased less, and control (8.4% versus 7.7%) even slightly decreased in
low- and middle-income countries. CONCLUSIONS: Global hypertension disparities
are large and increasing. Collaborative efforts are urgently needed to combat the
emerging hypertension burden in low- and middle-income countries.
PMID- 27502909
TI - Still on the Road to Worldwide Hypertension Control.
PMID- 27502911
TI - Letter by Aparci et al Regarding Article, "Characterization of Myocardial
Repolarization Reserve in Adolescent Females With Anorexia Nervosa".
PMID- 27502912
TI - Response by Padfield and Krahn to Letter Regarding Article, "Characterization of
Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa".
PMID- 27502913
TI - Letter by Papalia and Okonko Regarding Article, "Drp1-Dependent Mitochondrial
Autophagy Plays a Protective Role Against Pressure Overload-Induced Mitochondrial
Dysfunction and Heart Failure".
PMID- 27502914
TI - Response by Shirakabe et al to Letter Regarding Article, "Drp1-Dependent
Mitochondrial Autophagy Plays a Protective Role Against Pressure Overload-Induced
Mitochondrial Dysfunction and Heart Failure".
PMID- 27502915
TI - Letter by Carlstrom and Lundberg Regarding Article, "SIRT3-AMP-Activated Protein
Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and Normalizes
Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection
Fraction".
PMID- 27502916
TI - Response by Lai and Gladwin to Letter Regarding Article, "SIRT3-AMP-Activated
Protein Kinase Activation by Nitrite and Metformin Improves Hyperglycemia and
Normalizes Pulmonary Hypertension Associated With Heart Failure With Preserved
Ejection Fraction".
PMID- 27502917
TI - Assessment of a cytomegalovirus serology dual-testing strategy in hematopoietic
stem cell transplant recipients.
AB - BACKGROUND: Accurate determination of recipient cytomegalovirus (CMV) serostatus
before allogeneic hematopoietic stem cell transplantation (HSCT) is critical, as
it is the most important predictor of post-transplant CMV infection and remains
associated with non-relapse mortality. The purpose of this study was to assess a
recipient dual-testing strategy before HSCT. METHODS: CMV serologic testing was
performed before allogeneic HSCT using 2 different assays: reference laboratory
(RL) and American Red Cross (ARC). In all cases, blood samples were obtained for
RL testing either before ARC testing (median 130 days before HSCT [range 12
2594]) or at the same time (median 25 days before HSCT [range 8-129]). The
results of serologic testing were correlated with CMV viremia post HSCT. RESULTS:
Of 287 recipients evaluated, 76 (26.5%) had discordant results, of which 74
(97.4%) tested RL-/ARC+. Ten had RL and ARC testing performed on simultaneously
obtained samples, 3 of which (30%) were discordant (3 [100%] RL-/ARC+). Acute
myeloid leukemia and receipt of blood product transfusion in the interval between
testing were associated with RL-/ARC+ discordance. Correlation with viremia after
HSCT suggested that RL-/ARC+ discordance was caused by detection of anti-CMV
immunoglobulin transferred in transfused blood products and reduced specificity
of the ARC assay. CONCLUSION: CMV-seronegative hematopoietic stem cell transplant
recipients may be misclassified as seropositive if testing is performed after
receipt of blood products or when using assays optimized for sensitivity at the
expense of specificity. This misclassification may negatively affect post-HSCT
outcomes for individual patients and studies that rely on accurate CMV serology
reporting.
PMID- 27502918
TI - Abstracts of the German STI-Congress and Leopoldina-Symposium 2016, 06.
09.07.2016, Berlin.
PMID- 27502919
TI - The untold story of IFN-gamma in cancer biology.
AB - Interferon (IFN)-gamma is the uppermost cytokine implicated in anti-tumor
immunity. With its cytostatic, pro-apoptotic and immune-provoking effects, IFN
gamma plays a central role in the recognition and elimination of transformed
cells. Considering well-characterized anti-tumor effects of this cytokine, many
clinical trials and immunotherapy approaches have been designed to reinforce IFN
gamma-mediated immunity for different types of cancer. However, the outcomes were
not satisfactory and leaded to questioning of alternative actions of IFN-gamma.
Many regulatory pathways can be induced by IFN-gamma to protect the normal
tissues from collateral damage and to facilitate the re-establishment of
homeostasis. Nevertheless, malignant cells can take the advantage of IFN-gamma as
an inducer of mediators inhibiting anti-tumor immune reactions. In addition,
under the influence of tumor-derived factors, certain types of immune cells are
also licensed by IFN-gamma to perform regulatory actions. This review focuses on
the immune modulatory functions of IFN-gamma in cancer as an alternative story to
be told.
PMID- 27502920
TI - Infant and young child feeding practices differ by ethnicity of Vietnamese
mothers.
AB - BACKGROUND: Limited studies have examined ethnic variation in breastfeeding and
complementary feeding practices in developing countries. This study investigated
ethnic variation in feeding practices in mothers with children 0-23 months old in
Vietnam. METHODS: We used data on 1875 women who came from the ethnic majority,
Kinh (n = 989, randomly sampled from 9875 surveyed Kinh mothers, 10 % from each
province) and three ethnic minorities: E De-Mnong (n = 309), Thai-Muong (n = 229)
and Tay-Nung (n = 348). Ethnic minorities were compared with the Kinh group using
logistic regression model. RESULTS: Prevalence of breastfeeding initiation within
an hour of birth was 69 % in Thai-Muong, but ~50 % in other ethnicities. In
logistic regression, the prevalence of breastfeeding within one hour was lower in
Tay-Nung (OR: 0.54; 95 % CI: 0.38, 0.77) than the majority Kinh. Prevalence of
exclusive breastfeeding under 6 months was 18, 10, 17, and 33 % in Kinh, Thai
Muong, Tay-Nung, and E De-Mnong, respectively; compared to the majority Kinh, the
prevalence was lower in Thai-Muong (OR: 0.42; 95 % CI: 0.25, 0.71) and higher in
E De-Mnong (OR: 1.99; 95 % CI: 1.04, 3.82). Overall prevalence of bottle feeding
in Thai-Muong and E De-Mnong (~20 %) was lower than in Kinh (~33 %): Thai-Muong
(OR: 0.50; 95 % CI: 0.37, 0.68) and E De-Mnong (OR: 0.69; 95 % CI: 0.50, 0.95).
Compared with Kinh (75 %), fewer ethnic minority children received minimum
acceptable diets (33 % in Thai-Muong, 46 % in E De-Mnong, and 52 % in Tay-Nung; P
< 0.05). Prevalence of minimum acceptable diet (met both dietary frequency and
diversity) was lower in Thai-Muong (OR: 0.23; 95 % CI: 0.11, 0.46), Tay-Nung (OR:
0.52; 95 % CI: 0.39, 0.69), and E De-Mnong (OR: 0.55; 95 % CI: 0.33, 0.89) than
the majority Kinh. CONCLUSIONS: Breastfeeding practices were suboptimal and
differed by ethnicity, which suggests need for tailored interventions at multiple
levels to address ethnic-specific challenges and norms. Complementary feeding
practices were less optimal among ethnic minorities compared to Kinh, which
suggests need for broad intervention including improved food availability,
accessibility, and security.
PMID- 27502921
TI - Postoperative chemoradiotherapy versus chemotherapy for R0 resected gastric
cancer with D2 lymph node dissection: an up-to-date meta-analysis.
AB - BACKGROUND: This meta-analysis aims to provide more evidence on the role of
postoperative chemoradiotherapy (CRT) for gastric cancer (GC) patients in Asian
countries where D2 lymphadenectomy is prevalent. METHODS: We conducted a
systematic review of randomized controlled trials (RCTs), extracted data of
survival and toxicities, and pooled data to evaluate the efficacy and toxicities
of CRT compared with chemotherapy (CT) after D2 lymphadenectomy. RESULTS: A total
of 960 patients from four RCTs were selected. The results showed that
postoperative CRT significantly reduced loco-regional recurrence rate (LRRR: RR =
0.50, 95 % CI = 0.34-0.74, P = 0.0005) and improved disease-free survival (DFS:
HR = 0.73, 95 % CI = 0.60-0.89, P = 0.002). However, CRT did not affect distant
metastasis rate (DMR: RR = 0.81, 95 % CI = 0.60-1.08, P = 0.15) and overall
survival (OS: HR = 0.91, 95 % CI = 0.74-1.11, P = 0.34). The main grade 3-4
toxicities manifested no significant differences between the two groups.
CONCLUSIONS: Overall, CRT after D2 lymphadenectomy may reduce LRRR and prolong
DFS. The role of postoperative CRT should be further investigated in the
population with high risk of loco-regional recurrence.
PMID- 27502922
TI - Disentangling psychopathology, substance use and dependence: a factor analysis.
AB - BACKGROUND: The notion that substance use can induce symptoms of depression and
anxiety is influential in clinical practice, however questions remain about the
empirical support for this hypothesis. METHODS: We analysed mental health and
substance dependence screening records for 280 outpatients in addictions
treatment. Item-level data for depression (PHQ-9), anxiety (GAD-7), severity of
dependence (SDS) and self-reported weekly substance use were studied using factor
analysis and correlations. Symptom-level associations between substance use and
psychological distress symptoms were examined after controlling for underlying
levels of psychopathology. RESULTS: We obtained a two-factor solution accounting
for approximately 48 % of total variance. Depression and anxiety symptoms loaded
onto a single psychopathology factor. Severity of dependence (SDS) and substance
use measures loaded onto a distinct but correlated factor. After controlling for
latent levels of psychopathology, the only remaining symptom-level associations
were impaired concentration linked to cannabis use and irritability linked to
alcohol use. Dependence (SDS) was prominently associated with depressive
rumination, and negatively correlated with residual anxiety symptoms related to
substance use (e.g., craving). CONCLUSIONS: Overall, this analysis supports a
psychological understanding of comorbidity; with dependence, craving, negative
reinforcement and rumination as key variables.
PMID- 27502923
TI - Role of plant MicroRNA in cross-species regulatory networks of humans.
AB - BACKGROUND: It has been found that microRNAs (miRNAs) can function as a
regulatory factor across species. For example, food-derived plant miRNAs may pass
through the gastrointestinal (GI) tract, enter into the plasma and serum of
mammals, and interact with endogenous RNAs to regulate their expression. Although
this new type of regulatory mechanism is not well understood, it provides a fresh
look at the relationship between food consumption and physiology. To investigate
this new type of mechanism, we conducted a systematic computational study to
analyze the potential functions of these dietary miRNAs in the human body.
RESULTS: In this paper, we predicted human and plant target genes using RNAhybrid
and set some criteria to further filter them. Then we built the cross-species
regulatory network according to the filtered targets, extracted central nodes by
PageRank algorithm and built core modules. We summarized the functions of these
modules to three major categories: ion transport, metabolic process and stress
response, and especially some target genes are highly related to ion transport,
polysaccharides and the lipid metabolic process. Through functional analysis, we
found that human and plants have similar functions such as ion transport and
stress response, so our study also indicates the existence of a close link
between exogenous plant miRNA targets and digestive/urinary organs. CONCLUSIONS:
According to our analysis results, we suggest that the ingestion of these plant
miRNAs may have a functional impact on consuming organisms in a cross-kingdom
way, and the dietary habit may affect the physiological condition at a genetic
level. Our findings may be useful for discovering cross-species regulatory
mechanism in further study.
PMID- 27502925
TI - Lumbar puncture simulation in pediatric residency training: improving procedural
competence and decreasing anxiety.
AB - BACKGROUND: Pediatric residents must become proficient with performing a lumbar
puncture (LP) during training. Residents have traditionally acquired LP skills by
observing the procedure performed by a more senior resident or staff physician
and then attempting the procedure themselves. This process can result in variable
procedural skill acquisition and trainee discomfort. This study assessed changes
in resident procedural skill and self-reported anxiety when residents were
provided with an opportunity to participate in an interactive training session
and practice LPs using a simulator. METHODS: All pediatric residents at our
institution were invited to participate. Residents were asked to report their
post-graduate year (PGY), prior LP attempts and self-reported anxiety scores as
measured by the standardized State-Trait Anxiety Inventory - State Anxiety Scale
(STAI-S) prior to completing an observed pre-test using an infant-sized LP
simulator. Staff physicians observed and scored each resident's procedural skill
using a previously published 21-point scoring system. Residents then participated
in an interactive lecture on LP technique and were given an opportunity for staff
supervised, small group simulator-based practice within 1 month of the pre-test.
Repeat post-test was performed within 4 months. RESULTS: Of the pediatric
residents who completed the pre-test (N = 20), 16/20 (80 %) completed both the
training session and post-test. Their PGY training level was: PGY1 (38 %), PGY2
(25 %), PGY3 (25 %) or PGY4 (12 %). Procedural skill improved in 15/16 residents
(paired t-test; p < 0.001), driven by a significant improvement in skill for
residents in PGY1 (P = 0.015) and PGY2 (p = 0.003) but not PGY3 or PGY4. Overall
anxiety scores were higher at baseline than at post testing (mean +/- SD; 44.8 +/
12.1 vs 39.7 +/- 9.4; NS) however only PGY1 residents experienced a significant
reduction in anxiety (paired t-test, p = 0.04). CONCLUSION: LP simulation
training combined with an interactive training session may be a useful tool for
improving procedural competence and decreasing anxiety levels, particularly among
those at an earlier stage of residency training.
PMID- 27502924
TI - Role of different Culicoides vectors (Diptera: Ceratopogonidae) in bluetongue
virus transmission and overwintering in Sardinia (Italy).
AB - BACKGROUND: Bluetongue (BT) epidemics have affected the Mediterranean island of
Sardinia since 2000. While Culicoides imicola represents the main bluetongue
virus (BTV) vector, other European Culicoides biting midges, possibly implicated
in virus transmission, have been detected here. Understanding their distribution,
seasonal abundance, and infection rates is necessary to predict disease incidence
and spread across coastal and inland areas, and to define their role in virus
overwintering. METHODS: Biting midge abundance was determined by light traps on
selected farms representing diverse climatic conditions of Sardinia. Livestock
associated Culicoides species were morphologically and molecularly identified.
Infection rates in prevailing midge species captured in 2013 during a BTV-1
outbreak were determined using RT-qPCR based virus detection in insect body
pools, supplemented by specific body region analyses. The seasonal infection
prevalence in Culicoides samples collected in 2001 in a BTV-2 affected farm was
also determined. RESULTS: The Newsteadi complex (C. newsteadi species A and
species B) prevailed among all biting midge species (47.7 %), followed by C.
imicola (27.8 %) and the Obsoletus complex (C. obsoletus and C. scoticus) (17.6
%). Whilst Culicoides imicola was more abundant along the coast, the Newsteadi
complex was frequently collected at higher altitude and the Obsoletus complex was
notably associated to cattle farms. Culicoides pulicaris and C. punctatus
abundance was found to be marginal in all farms. BTV was detected in parous
female samples of all these species, and the full dissemination of the virus
within the body of C. imicola, C. obsoletus, C. scoticus, and Newsteadi complex
species was confirmed by analyses of thorax and head, containing salivary glands.
Higher infection rates were associated with C. scoticus, C. newsteadi species A
and species B, compared to C. imicola. The virus was detected in C. newsteadi
species A and C. obsoletus in winter and spring, whereas it was mainly found in
summer and autumn in C. imicola. CONCLUSIONS: In Sardinia, bluetongue virus is
transmitted by multiple Culicoides vectors, including C. imicola and the
Newsteadi complex being the most important. The Newsteadi complex and other midge
species can play an important role in internal areas and are likely to be
directly involved in virus overwintering.
PMID- 27502926
TI - A volatolomic approach for studying plant variability: the case of selected
Helichrysum species (Asteraceae).
AB - The species of Helichrysum sect. Stoechadina (Asteraceae) are well-known for
their secondary metabolite content and the characteristic aromatic bouquets. In
the wild, populations exhibit a wide phenotypic plasticity which makes critical
the circumscription of species and infraspecific ranks. Previous investigations
on Helichrysum italicum complex focused on a possible phytochemical typification
based on hydrodistilled essential oils. Aims of this paper are three-fold: (i)
characterizing the volatile profiles of different populations, testing (ii) how
these profiles vary across populations and (iii) how the phytochemical diversity
may contribute in solving taxonomic problems. Nine selected Helichrysum
populations, included within the H. italicum complex, Helichrysum litoreum and
Helichrysum stoechas, were investigated. H. stoechas was chosen as outgroup for
validating the method. After collection in the wild, plants were cultivated in
standard growing conditions for over one year. Annual leafy shoots were screened
in the post-blooming period for the emissions of volatile organic compounds
(VOCs) by means of headspace solid phase microextraction coupled with gas
chromatography and mass spectrometry (HS-SPME-GC/MS). The VOC composition
analysis revealed the production of overall 386 different compounds, with
terpenes being the most represented compound class. Statistical data processing
allowed the identification of the indicator compounds that differentiate the
single populations, revealing the influence of the geographical provenance area
in determining the volatile profiles. These results suggested the potential use
of VOCs as valuable diacritical characters in discriminating the Helichrysum
populations. In addition, the cross-validation analysis hinted the potentiality
of this volatolomic study in the discrimination of the Helichrysum species and
subspecies, highlighting a general congruence with the current taxonomic
treatment of the genus. The consistency between this phytochemical approach and
the traditional morphometrical analysis in studying the Helichrysum populations
supports the validity of the VOC profile in solving taxonomic problems.
PMID- 27502927
TI - Reproducibility of dalbavancin MIC test results and an updated surrogate accuracy
analysis of vancomycin MIC values to infer dalbavancin susceptibility (2014).
PMID- 27502928
TI - Design of the FemCure study: prospective multicentre study on the transmission of
genital and extra-genital Chlamydia trachomatis infections in women receiving
routine care.
AB - BACKGROUND: In women, anorectal infections with Chlamydia trachomatis (CT) are
about as common as genital CT, yet the anorectal site remains largely untested in
routine care. Anorectal CT frequently co-occurs with genital CT and may thus
often be treated co-incidentally. Nevertheless, post-treatment detection of CT at
both anatomic sites has been demonstrated. It is unknown whether anorectal CT may
play a role in post-treatment transmission. This study, called FemCure, in women
who receive routine treatment (either azithromycin or doxycycline) aims to
understand the post-treatment transmission of anorectal CT infections, i.e., from
their male sexual partner(s) and from and to the genital region of the same
woman. The secondary objective is to evaluate other reasons for CT detection by
nucleic acid amplification techniques (NAAT) such as treatment failure, in order
to inform guidelines to optimize CT control. METHODS: A multicentre prospective
cohort study (FemCure) is set up in which genital and/or anorectal CT positive
women (n = 400) will be recruited at three large Dutch STI clinics located in
South Limburg, Amsterdam and Rotterdam. The women self-collect anorectal and
vaginal swabs before treatment, and at the end of weeks 1, 2, 4, 6, 8, 10, and
12. Samples are tested for presence of CT-DNA (by NAAT), load (by quantitative
polymerase chain reaction -PCR), viability (by culture and viability PCR) and CT
type (by multilocus sequence typing). Sexual exposure is assessed by online self
administered questionnaires and by testing samples for Y chromosomal DNA. Using
logistic regression models, the impact of two key factors (i.e., sexual exposure
and alternate anatomic site of infection) on detection of anorectal and genital
CT will be assessed. DISCUSSION: The FemCure study will provide insight in the
role of anorectal chlamydia infection in maintaining the CT burden in the context
of treatment, and it will provide practical recommendations to reduce avoidable
transmission. Implications will improve care strategies that take account of
anorectal CT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02694497 .
PMID- 27502929
TI - The correlation between Toxoplasma gondii infection and prenatal depression in
pregnant women.
AB - Previous studies have demonstrated that latent toxoplasmosis is associated with
neuropsychiatric disorders. We evaluated the correlation between Toxoplasma
gondii infection and prenatal depression. In this case-control study, we enrolled
116 depressed pregnant women and 244 healthy controls. The Edinburgh Postpartum
Depression Scale (EPDS) was used to evaluate the depression symptom severity in
study participants. All participants were screened for the anti-Toxoplasma IgG by
enzyme-linked immunosorbent assay. Seroprevalence of T. gondii did not
significantly differ between the depressed pregnant women and healthy controls
(OR = 1.4; 95 % CI = 0.9-2.19; P = 0.142). T. gondii IgG titer was significantly
higher in depressed women (18.6 +/- 10.9 IUs) than those in the control group
(13.6 +/- 8.1 IUs) (z = -5.36, P < 0.001). The T. gondii-positive depressed women
showed a positive correlation of T. gondii IgG titer with the EPDS scores (r =
0.52; P < 0.01). The mean EPDS score was also significantly higher in the T.
gondii-positive depressed women (20.7 +/- 2.7) compared with the controls (18.36
+/- 2.7) (P < 0.001). The results obtained from the current study revealed that
T. gondii infection might affect susceptibility to depression and severity of
depressive symptoms in pregnant women, particularly in those patients who have
high antibody titers. Further study is required to fully elucidate the
characteristics and mechanisms of this association.
PMID- 27502930
TI - Etiology and clinical features of 229 cases of bloodstream infection among
Chinese HIV/AIDS patients: a retrospective cross-sectional study.
AB - Bloodstream infections (BSIs) are prevalent among people living with HIV/AIDS.
The etiology varies in different regions and different periods. We aimed to
survey the etiological and clinical features of BSIs in HIV patients in mainland
China. We assessed all HIV patients with a positive blood culture in a Chinese
teaching hospital from September 2009 through December 2014. We excluded those
with specimens likely to have been contaminated. We used Pearson's chi-squared
test to measure the differences in characteristics among subgroups of different
pathogens. Among 2442 Chinese HIV-seropositive inpatients, 229 (9.38 %)
experienced BSIs. The most common pathogens detected included Cryptococcus
neoformans (22.7 %), Penicillium marneffei (18.8 %), Mycobacterium tuberculosis
(15.3 %), and non-tuberculous mycobacterium (14.8 %). 30/229 (13.1 %) HIV
patients with BSIs had a poor prognosis. BSIs are prevalent in hospitalized
patients with HIV/AIDS in China. Fungi and mycobacteria are the predominant
pathogens.
PMID- 27502931
TI - Computed tomography findings associated with bacteremia in adult patients with a
urinary tract infection.
AB - The use of computed tomography (CT) in the diagnosis of urinary tract infection
(UTI) has rapidly increased recently at acute stage, but the CT findings
associated with bacteremia in UTI patients are unknown. 189 UTI patients were
enrolled who underwent a CT scan within 24 h after hospital admission. We
classified CT findings into eight types: a focal or multifocal wedge-shaped area
of hypoperfusion, enlarged kidneys, perinephric fat stranding, ureteritis or
pyelitis, complicated renal cyst, renal papillary necrosis, hydronephrosis, and
renal and perirenal abscess. A retrospective analysis was conducted to evaluate
the CT findings associated with bacteremia. The mean age of these patients was 60
+/- 17.2 years, and 93.1 % were women. Concurrent bacteremia was noted in 40.2 %
of the patients. Abnormal CT findings were noted in 96.3 % of the patients and
62.4 % had two or more abnormal findings. The most frequent abnormal CT finding
was a focal or multifocal wedge-shaped area of hypoperfusion (77.2 %), followed
by perinephric fat stranding (29.1 %). Perinephric fat stranding, hydronephrosis,
and the presence of two or more abnormal CT findings were significantly
associated with bacteremia in patients with community-acquired UTI. In the
multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95 %
confidence interval (CI) 1.009-1.062], two or more abnormal CT findings (OR
3.163; 95 % CI 1.334-7.498), and hydronephrosis (OR 13.160; 95 % CI 1.048
165.282) were significantly associated with bacteremia. Physicians should be
aware that appropriate early management is necessary to prevent fatality in
patients with these CT findings.
PMID- 27502933
TI - Dose-Adjusted EPOCH-R and Mid-Cycle High Dose Methotrexate for Patients with
Systemic Lymphoma and secondary CNS Involvement.
PMID- 27502932
TI - Comparison on cellular mechanisms of iron and cadmium accumulation in rice:
prospects for cultivating Fe-rich but Cd-free rice.
AB - Iron (Fe) is essential for rice growth and humans consuming as their staple food
but is often deficient because of insoluble Fe(III) in soil for rice growth and
limited assimilation for human bodies, while cadmium (Cd) is non-essential and
toxic for rice growth and humans if accumulating at high levels. Over-accumulated
Cd can cause damage to human bodies. Selecting and breeding Fe-rich but Cd-free
rice cultivars are ambitious, challenging and meaningful tasks for researchers.
Although evidences show that the mechanisms of Fe/Cd uptake and accumulation in
rice are common to some extent as a result of similar entry routes within rice,
an increasing number of researchers have discovered distinct mechanisms between
Fe/Cd uptake and accumulation in rice. This comprehensive review systematically
elaborates and compares cellular mechanisms of Fe/Cd uptake and accumulation in
rice, respectively. Mechanisms for maintaining Fe homeostasis and Cd
detoxicification are also elucidated. Then, effects of different fertilizer
management on Fe/Cd accumulation in rice are discussed. Finally, this review
enumerates various approaches for reducing grain Cd accumulation and enhancing Fe
content in rice. In summary, understanding of discrepant cellular mechanisms of
Fe/Cd accumulation in rice provides guidance for cultivating Fe-fortified rice
and has paved the way to develop rice that are tolerant to Cd stress, aiming at
breeding Fe-rich but Cd-free rice.
PMID- 27502934
TI - Does lymph node dissection during nephroureterectomy affect oncological outcomes
in upper tract urothelial carcinoma patients without suspicious lymph node
metastasis on preoperative imaging studies?
AB - PURPOSE: This study aimed to investigate the effects of lymph node dissection
(LND) on upper tract urothelial carcinoma (UTUC) without suspicious lymph node
(LN) metastasis on preoperative imaging studies. METHODS: From 1998 to 2012, 418
UTUC patients without suspicious LN metastasis on preoperative imaging studies
were included. Patients were divided into two groups according to the performance
of LND. The effects of LND on oncological outcomes were assessed after adjusting
other variables. The mean follow-up duration was 69 months. RESULTS: Among the
132 patients who underwent LND, LN metastasis was pathologically identified in 16
patients (12.1 %). The median number of resected LNs for patients who underwent
LND was 7. On multivariate analysis, the number of resected LNs and pathologic T
stage was significant predictors of LN metastasis. The 5-year recurrence-free
survival was 76.4 % for patients without LND and 65.4 % for patients with LND (p
= 0.126). In addition, there was no difference in 5-year overall survival between
the 2 groups (without LND; 71.7 % vs. with LND; 72.1 %, p = 0.756). Multivariate
analysis showed that pathologic T stage, tumor grade, and lymphovascular invasion
were risk factors for recurrence. Age at surgery, tumor size, pathologic T stage,
tumor grade, and lymphovascular invasion were significantly associated with
overall survival. However, performance of LND was not associated with recurrence
and survival. CONCLUSIONS: LND could be selectively performed in patients with
clinically LN-negative UTUC based on patient/tumor characteristics and operative
findings although sufficient LNs should be removed if LND is to be performed.
PMID- 27502936
TI - Modified method to enhanced recovery of Toxocara cati larvae for the purposes of
diagnostic and therapeutic.
AB - Human toxocariasis, extraintestinal-migration of Toxocara species, is a worldwide
helminthic zoonosis in many places of the undeveloped countries. Toxocara cati is
one of the common helminths in cats and it is a potentially preventable disease.
Its diagnosis and treatment depend on the demonstration of specific excretory
secretory Toxocara antibodies from Toxocara larvae by immunological assays. This
study provides a simple manual technique which can be performed in any laboratory
for recovering a large number of Toxocara cati larvae from the thick-shelled
eggs. The devices that are required contain a manual homogenizer and a filter
membrane of 40 MUm mesh; the rest of materials and solutions is standard
laboratory ware. In the modified method the larval yields were 2.7 times higher
(3000 larval/ml) and the time spent in performing the modified method was shorter
(75 min). Further benefits over already techniques are the easy and repeatable,
inexpensive and convenient materials, simplicity to perform and require less time
for recovery of Toxocara cati larvae for subsequent cultivation and harvest of
the larval excretory-secretory antigens for diagnostic or treatment purposes.
PMID- 27502935
TI - Cytoreductive radical prostatectomy in metastatic prostate cancer: Does it really
make sense?
AB - PURPOSE: Surgical removal of the primary tumor in metastatic prostate cancer
(mPCa) is becoming a hotly debated issue. The purpose of this review was to
summarize the current knowledge on cytoreductive radical prostatectomy (cRP) in
this setting. MATERIALS AND METHODS: We performed a non-systematic Medline/PubMed
literature search of articles published in the field between January 2000 and
April 2015. RESULTS: Cytoreductive surgery has demonstrated its benefit in
various malignancies with a solid biological rationale to justify its assessment
in mPCa. cRP appears as a safe and feasible procedure in expert hands and well
selected patients. A growing body of evidence suggests a survival benefit for
patients undergoing cRP as a part of a multimodal approach compared to those
treated with systemic treatment alone. Nevertheless, little is known about the
best clinical and tumor characteristics for the selection of patients most likely
to benefit from cRP. The current literature is based on retrospective studies
with small cohorts and limited follow-up or large uncontrolled population-based
studies. CONCLUSIONS: Data from various other malignancies together with the
biological rationale and preliminary results in PCa suggest that cytoreductive
surgery may be an option in some mPCa patients. The lack of randomized controlled
trials and the low level of evidence in the current literature preclude any firms
conclusion on the benefit of cRP in mPCa. Ongoing phase II and future phase III
studies are mandatory to define the exact role of cRP in mPCa and to identify the
patients who are most likely to benefit from cRP.
PMID- 27502937
TI - Winter is coming: The recurring risk of carbon monoxide poisoning.
PMID- 27502938
TI - Abnormal Expression of FBXL20 in Refractory Epilepsy Patients and a Pilocarpine
Induced Rat Model.
AB - E3 ubiquitin ligases are important protein-modifying enzymes involved in the
pathogenesis of a variety of neurodegenerative diseases. F-box and leucine-rich
repeat protein 20 (FBXL20), an E3 ubiquitin ligase widely expressed in the
central nervous system, plays an important role in the ubiquitin-dependent
degradation of regulating synaptic membrane exocytosis 1 (RIM1), which is an
important factor in the release of synaptic vesicles. FBXL20 has been associated
with a variety of neurodegenerative diseases; thus, we hypothesized that FBXL20
is involved in the development of epilepsy. Herein, we used immunofluorescence
staining, immunohistochemistry and western blotting to determine the expression
pattern of FBXL20 in temporal lobe epilepsy patients and pilocarpine-induced
epilepsy animal models. We also injected SD rats with lentivirus-vector mediated
overexpression of FBXL20. The results showed that FBXL20 is expressed in the
membrane and the cytoplasm of cortical neurons, and overexpression of FBXL20
decreased the onset level of spontaneous seizure, the frequency and duration of
seizures. Additionally, FBXL20 protein level was decreased but RIM1 protein level
was increased in the epileptic group compared with the LV-FBXL20 and LV-GFP
group. These findings in humans were consistent with the results from a
pilocarpine-induced animal model of chronic epilepsy. Thus, abnormal expression
of FBXL20 might play an important role in the development of epilepsy.
PMID- 27502939
TI - The Search for New Screening Models of Pharmacoresistant Epilepsy: Is Induction
of Acute Seizures in Epileptic Rodents a Suitable Approach?
AB - Epilepsy, a prevalent neurological disease characterized by spontaneous recurrent
seizures (SRS), is often refractory to treatment with anti-seizure drugs (ASDs),
so that more effective ASDs are urgently needed. For this purpose, it would be
important to develop, validate, and implement new animal models of
pharmacoresistant epilepsy into drug discovery. Several chronic animal models
with difficult-to-treat SRS do exist; however, most of these models are not
suited for drug screening, because drug testing on SRS necessitates laborious
video-EEG seizure monitoring. More recently, it was proposed that, instead of
monitoring SRS, chemical or electrical induction of acute seizures in epileptic
rodents may be used as a surrogate for testing the efficacy of novel ASDs against
refractory SRS. Indeed, several ASDs were shown to lose their efficacy on acute
seizures, when such seizures were induced by pentylenetetrazole (PTZ) in
epileptic rather than nonepileptic rats, whereas this was not observed when using
the maximal electroshock seizure test. Subsequent studies confirmed the loss of
anti-seizure efficacy of valproate against PTZ-induced seizures in epileptic
mice, but several other ASDs were more potent against PTZ in epileptic than
nonepileptic mice. This was also observed when using the 6-Hz model of partial
seizures in epileptic mice, in which the potency of levetiracetam, in particular,
was markedly increased compared to nonepileptic animals. Overall, these
observations suggest that performing acute seizure tests in epileptic rodents
provides valuable information on the pharmacological profile of ASDs, in
particular those with mechanisms inherent to disease-induced brain alterations.
However, it appears that further work is needed to define optimal approaches for
acute seizure induction and generation of epileptic/drug refractory animals that
would permit reliable screening of new ASDs with improved potential to provide
seizure control in patients with pharmacoresistant epilepsy.
PMID- 27502940
TI - Interactions between Glu-1 and Glu-3 loci and associations of selected molecular
markers with quality traits in winter wheat (Triticum aestivum L.) DH lines.
AB - The quality of wheat depends on a large complex of genes and environmental
factors. The objective of this study was to identify quantitative trait loci
controlling technological quality traits and their stability across environments,
and to assess the impact of interaction between alleles at loci Glu-1 and Glu-3
on grain quality. DH lines were evaluated in field experiments over a period of 4
years, and genotyped using simple sequence repeat markers. Lines were analysed
for grain yield (GY), thousand grain weight (TGW), protein content (PC), starch
content (SC), wet gluten content (WG), Zeleny sedimentation value (ZS),
alveograph parameter W (APW), hectolitre weight (HW), and grain hardness (GH). A
number of QTLs for these traits were identified in all chromosome groups. The Glu
D1 locus influenced TGW, PC, SC, WG, ZS, APW, GH, while locus Glu-B1 affected
only PC, ZS, and WG. Most important marker-trait associations were found on
chromosomes 1D and 5D. Significant effects of interaction between Glu-1 and Glu-3
loci on technological properties were recorded, and in all types of this
interaction positive effects of Glu-D1 locus on grain quality were observed,
whereas effects of Glu-B1 locus depended on alleles at Glu-3 loci. Effects of Glu
A3 and Glu-D3 loci per se were not significant, while their interaction with
alleles present at other loci encoding HMW and LMW were important. These results
indicate that selection of wheat genotypes with predicted good bread-making
properties should be based on the allelic composition both in Glu-1 and Glu-3
loci, and confirm the predominant effect of Glu-D1d allele on technological
properties of wheat grains.
PMID- 27502941
TI - The genome-scale DNA-binding profile of BarR, a beta-alanine responsive
transcription factor in the archaeon Sulfolobus acidocaldarius.
AB - BACKGROUND: The Leucine-responsive Regulatory Protein (Lrp) family is a
widespread family of regulatory transcription factors in prokaryotes. BarR is an
Lrp-like transcription factor in the model archaeon Sulfolobus acidocaldarius
that activates the expression of a beta-alanine aminotransferase gene, which is
involved in beta-alanine degradation. In contrast to classical Lrp-like
transcription factors, BarR is not responsive to any of the alpha-amino acids but
interacts specifically with beta-alanine. Besides the juxtaposed beta-alanine
aminotransferase gene, other regulatory targets of BarR have not yet been
identified although beta-alanine is the precursor of coenzyme A and thus an
important central metabolite. The aim of this study is to extend the knowledge of
the DNA-binding characteristics of BarR and of its corresponding regulon from a
local to a genome-wide perspective. RESULTS: We characterized the genome-wide
binding profile of BarR using chromatin immunoprecipation combined with high
throughput sequencing (ChIP-seq). This revealed 21 genomic binding loci. High
enrichment binding regions were validated to interact with purified BarR protein
in vitro using electrophoretic mobility shift assays and almost all targets were
also shown to harbour a conserved semi-palindromic binding motif. Only a small
subset of enriched genomic sites are located in intergenic regions at a relative
short distance to a promoter, and qRT-PCR analysis demonstrated that only one
additional operon is under activation of BarR, namely the glutamine synthase
operon. The latter is also a target of other Lrp-like transcription factors.
Detailed inspection of the BarR ChIP-seq profile at the beta-alanine
aminotransferase promoter region in combination with binding motif predictions
indicate that the operator structure is more complicated than previously
anticipated, consisting of multiple (major and auxiliary) operators. CONCLUSIONS:
BarR has a limited regulon, and includes also glutamine synthase genes besides
the previously characterized beta-alanine aminotransferase. Regulation of
glutamine synthase is suggestive of a link between beta-alanine and alpha-amino
acid metabolism in S. acidocaldarius. Furthermore, this work reveals that the
BarR regulon overlaps with that of other Lrp-like regulators.
PMID- 27502942
TI - Clinical comparison of the two-stranded single and four-stranded double Krackow
techniques for acute Achilles tendon ruptures.
AB - PURPOSE: Several different Krackow stitch configurations have been used for acute
Achilles tendon rupture repair. Although several biomechanical studies compared
different Krackow stitch configurations, to our knowledge, no previous studies
compared the clinical outcome of these different suture methods. Therefore, in
this study, we aimed to compare the clinical outcomes and complications of the
two-stranded single and four-stranded double Krackow techniques. METHODS: Sixty
eight consecutive patients who underwent open repair by using the four-stranded
double Krackow (33 patients, group A) or the two-stranded single Krackow (35
patients, group B) techniques between September 2011 and August 2014 were
reviewed retrospectively. The isokinetic strength of plantar flexion and
dorsiflexion of both ankles was assessed on a Cybex dynamometer 3 and 6 months
after surgery. Clinical outcomes were evaluated 3, 6, and 12 months post
operatively. RESULTS: No significant differences were found between the groups
regarding patient demographics or activity levels prior to treatment. Significant
differences in the Achilles tendon Total Rupture Score, the American Orthopaedic
Foot and Ankle Society Ankle-Hindfoot score, or the four-point Boyden scale were
not found at any time during follow-up. Rerupture occurred only in one patient
from group A. No significant differences were observed between the groups
regarding the isokinetic plantar flexion and dorsiflexion strength at any time or
any test speed. CONCLUSION: Equally favourable clinical outcomes and isokinetic
muscle strength and a low complication rate were achieved with the two-stranded
single Krackow technique as compared with the four-stranded double Krackow
technique for acute Achilles tendon rupture repair. LEVEL OF EVIDENCE: III.
PMID- 27502943
TI - Possible Impact of Incremental Cost-Effectiveness Ratio (ICER) on Decision Making
for Cancer Screening in Hong Kong: A Systematic Review.
AB - OBJECTIVES: The aim of this paper was to critically review the literature on the
cost effectiveness of cancer screening interventions, and examine the incremental
cost-effectiveness ratios (ICERs) that may influence government recommendations
on cancer screening strategies and funding for mass implementation in the Hong
Kong healthcare system. METHODS: We conducted a literature review of cost
effectiveness studies in the Hong Kong population related to cancer screening
published up to 2015, through a hand search and database search of PubMed, Web of
Science, Embase, and OVID Medline. Binary data on the government's decisions were
obtained from the Cancer Expert Working Group, Department of Health. Mixed-effect
logistic regression analysis was used to examine the impact of ICERs on decision
making. Using Youden's index, an optimal ICER threshold value for positive
decisions was examined by area under receiver operating characteristic curve
(AUC). RESULTS: Eight studies reporting 30 cost-effectiveness pairwise
comparisons of population-based cancer screening were identified. Most studies
reported an ICER for a cancer screening strategy versus a comparator with
outcomes in terms of cost per life-years (55.6 %), or cost per quality-adjusted
life-years (55.6 %). Among comparisons with a mean ICER of US$102,931 (range 800
715,137), the increase in ICER value by 1000 was associated with decreased odds
(odds ratio 0.990, 0.981-0.999; p = 0.033) of a positive recommendation. An
optimal ICER value of US$61,600 per effectiveness unit yielded a high sensitivity
of 90 % and specificity of 85 % for a positive recommendation. A lower ICER
threshold value of below US$8044 per effectiveness unit was detected for a
positive funding decision. CONCLUSIONS: Linking published evidence to Government
recommendations and practice on cancer screening, ICERs influence decisions on
the adoption of health technologies in Hong Kong. The potential ICER threshold
for recommendation in Hong Kong may be higher than those of developed countries.
PMID- 27502948
TI - Neurally adjusted ventilatory assist (NAVA) in preterm newborn infants with
respiratory distress syndrome-a randomized controlled trial.
AB - Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator synchrony
during invasive ventilation and leads to lower peak inspiratory pressures (PIP)
and oxygen requirements. The aim of this trial was to compare NAVA with current
standard ventilation in preterm infants in terms of the duration of invasive
ventilation. Sixty infants born between 28 + 0 and 36 + 6 weeks of gestation and
requiring invasive ventilation due to neonatal respiratory distress syndrome
(RDS) were randomized to conventional ventilation or NAVA. The median durations
of invasive ventilation were 34.7 h (quartiles 22.8-67.9 h) and 25.8 h (15.6-52.1
h) in the NAVA and control groups, respectively (P = 0.21). Lower PIPs were
achieved with NAVA (P = 0.02), and the rapid reduction in PIP after changing the
ventilation mode to NAVA made following the predetermined extubation criteria
challenging. The other ventilatory and vital parameters did not differ between
the groups. Frequent apneas and persistent pulmonary hypertension were conditions
that limited the use of NAVA in 17 % of the patients randomized to the NAVA
group. Similar cumulative doses of opiates were used in both groups (P = 0.71).
CONCLUSIONS: NAVA was a safe and feasible ventilation mode for the majority of
preterm infants suffering from RDS, but the traditional extubation criteria were
not clinically applicable during NAVA. WHAT IS KNOWN: * NAVA improves patient
ventilator synchrony during invasive ventilation. * Lower airway pressures and
oxygen requirements are achieved with NAVA during invasive ventilation in preterm
infants by comparison with conventional ventilation. What is new: * Infants
suffering from PPHN did not tolerate NAVA in the acute phase of their illness. *
The traditional extubation criteria relying on inspiratory pressures and
spontaneous breathing efforts were not clinically applicable during NAVA.
PMID- 27502949
TI - Binding of transition metals to monosilicic acid in aqueous and xylem (Cucumis
sativus L.) solutions: a low-T electron paramagnetic resonance study.
AB - The supplementation of monosilicic acid [Si(OH)4] to the root growing medium is
known to protect plants from toxic levels of iron (Fe), copper (Cu) and manganese
(Mn), but also to mitigate deficiency of Fe and Mn. However, the physicochemical
bases of these alleviating mechanisms are not fully understood. Here we applied
low-T electron paramagnetic resonance (EPR) spectroscopy to examine the formation
of complexes of Si(OH)4 with Mn(2+), Fe(3+), and Cu(2+) in water and in xylem sap
of cucumber (Cucumis sativus L.) grown without or with supply of Si(OH)4. EPR,
which is also useful in establishing the redox state of these metals, was
combined with measurements of total concentrations of metals in xylem sap by
inductive coupled plasma. Our results show that Si(OH)4 forms coordination bonds
with all three metals. The strongest interactions of Si(OH)4 appear to be with
Cu(2+) (1/1 stoichiometry) which might lead to Cu precipitation. In line with
this in vitro findings, Si(OH)4 supply to cucumber resulted in dramatically lower
concentration of this metal in the xylem sap. Further, it was demonstrated that
Si(OH)4 supplementation causes pro-reductive changes that contribute to the
maintenance of Fe and, in particular, Mn in the xylem sap in bioavailable 2+
form. Our results shed more light on the intertwined reactions between Si(OH)4
and transition metals in plant fluids (e.g. xylem sap).
PMID- 27502950
TI - Patient characteristics in a return to work programme for common mental
disorders: a cross-sectional study.
AB - BACKGROUND: Mental health problems are a growing cause of sickness absence. There
are programmes in many countries to facilitate return to work (RTW) after
sickness absence. In Norway, there has been some controversy about patients on
sick-leave being prioritized over other patient groups, such as those with more
severe diagnoses. However, it is not clear whether patients in RTW programmes
actually do differ from patients in regular services. METHODS: This study
compared 270 patients treated in an RTW outpatient clinic and 86 patients treated
in a regular outpatient clinic, both in specialized mental health care, on
patient characteristics, history of treatment and mental health status. Analyses
of differences between groups were done by ANOVA tests, chi-square test and
logistic regression. RESULTS: Patients in the RTW clinic had lower scores on the
Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM). There was no
difference in health-related quality of life. RTW patients were somewhat older
and more likely to live in relationships and have children, and they had higher
incomes. Work participation, previous psychiatric hospitalization and present
diagnosis contributed uniquely to an explanation of which patients were included
in the respective clinics. The RTW clinic seems to reach its intended target
group. Almost all of the patients in this group participated in the work arena,
and their psychopathologies were clearly dominated by common mental disorders.
Most RTW patients' general practitioners had followed them fairly closely in the
year before referral, suggesting previous attempts at treatment in primary care
settings. CONCLUSIONS: Relative to outpatients in a specialized mental health
care setting, RTW patients had lower symptoms, but still in the same moderate
range of severity. They suffered the same reduction in quality of life. Almost
all of the RTW patients were diagnosed with illnesses that can be treated
effectively, about half of them had recurring mental health problems and many of
them had been treated in primary care settings before referral. These findings
indicate that this group has significant health problems that can benefit from
treatment in specialized health care settings.
PMID- 27502951
TI - The Correlation Between Arterial Lactate and Venous Lactate in Patients With
Sepsis and Septic Shock.
AB - BACKGROUND: Applying peripheral venous lactate instead of arterial lactate in
clinical practice is questionable because of deviation between both values. We
aimed to find the relationship between the arterial lactate and the peripheral
venous lactate before reasoned that the venous lactate could be used in
substitution to the arterial lactate in sepsis. METHODS: We conducted a
prospective, cross-sectional study at a university hospital. The patients with
sepsis in ICU who required lactate level monitoring were enrolled in this
research. The correlation and agreement between arterial lactate (A-LACT) and
peripheral venous lactate (V-LACT) were the primary outcomes. RESULTS: A total of
63 paired samples were collected. The A-LACT and V-LACT were strongly correlated
( r = .934, P < .0001, r2 = .873). The regression equation was A-LACT = (0.934 *
V-LACT) - 0.236. The mean difference between V-LACT and A-LACT was 0.66 +/- 1.53
mmol/L. The 95% limits of agreement were between -3.66 and 2.33 mmol/L. The V
LACT >= 4 mmol/L can predict A-LACT level >= 4 mmol/L with 87.5% sensitivity and
91.5% specificity, and the area under receiver operating characteristic curve was
0.948. CONCLUSION: The present study demonstrated a strong correlation between A
LACT and V-LACT, but an agreement between both parameters was poor. We suggest
not to use the V-LACT in substitution to the A-LACT in sepsis regarding the
absolute value and clearance rate, but the V-LACT >= 4.5 mmol/L may be used for
predicting the A-LACT >= 4 mmol/L.
PMID- 27502952
TI - Sympatric reinforcement of reproductive barriers between Neotinea tridentata and
N. ustulata (Orchidaceae).
AB - Reinforcement is the process by which selection favors traits that decrease
mating between two incipient species in response to costly mating or the
production of maladapted hybrids, causing the evolution of greater reproductive
isolation between emerging species. I have studied a pair of orchids, Neotinea
tridentata and N. ustulata, to examine the level of postmating pre- and post
zygotic isolating mechanisms that maintain these species, and the degree to which
the boundary may still be permeable to gene flow. In this study, I performed
pollen tube growth rate experiments and I investigated pre- and post-zygotic
barriers by performing hand pollination experiments in order to evaluate fruit
set, embryonate seed set and seed germination rates by intra- and interspecific
crosses. Fruit set, the percentage of embryonate seeds and germinability of
interspecific crosses were reduced compared to intraspecific pollinations,
showing significant differences between sympatric and allopatric populations.
While in allopatric populations the post-pollination isolation index ranged
between 0.40 and 0.11, in sympatric populations orchid pairs showed total
isolation due to post-pollination prezygotic barriers, guaranteed at the level of
pollen-stigma interactions. Indeed, in sympatric populations, pollen tubes
reached the ovary after 24 h in only 8 out of 45 plants; in the remaining cases,
the pollen tubes did not enter the ovary, and thus no fruit set occurred. This
pair of orchids is characterized by postmating pre-zygotic reproductive isolation
in sympatric populations that prevents the formation of hybrids. This mechanism
of speciation, starting in allopatry and triggering the reinforcement mechanisms
of reproductive isolation in secondary sympatry, is the most likely explanation
for the pattern of evolutionary transitions found in this pair of orchids.
PMID- 27502953
TI - Lead Modulates Calcium Entry and Beta-Adrenoceptors Signaling to Produce
Myometrial Relaxation in Rats.
AB - Modulation of myometrial spontaneity by lead acetate trihydrate (Pb) and its
regulatory pathways were studied in estrogenized rats. Isometric tension in
myometrial strips under a resting tension of 1 g was measured using data
acquisition system-based physiograph and Lab Chart Pro v7.3.7 software. Lead
produced a dose-dependent inhibitory effect on rat myometrium with a major effect
on phasic contractions compared to tonic contractions along with a reduction in
both amplitude and frequency of contraction. Lead (3 MUM) significantly (p <
0.05) reduced CaCl2, and 80 mM KDS induced contractile response while potentiated
the relaxant effect of phenylephrine. Based on our findings, it may be inferred
that lead blocks calcium entry through VDCC and/or stimulates beta-adrenoceptors
adenylyl cyclase-C-AMP pathway to produce inhibitory effect on rat myometrium.
PMID- 27502954
TI - Serum Macroelement and Microelement Concentrations in Patients with Polycystic
Ovary Syndrome: a Cross-Sectional Study.
AB - Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases.
However, its pathogenesis is unclear. We aim to explore the potential
relationships between serum macroelements/microelements and PCOS. A total of 1137
women were involved in the current study. PCOS was defined according to
ESHRE/ASRM, and complete blood samples were collected. Serum macroelements
(calcium and magnesium) and microelements (copper, zinc, and iron) were assayed
through atomic absorption spectrophotometry. PCOS patients had significantly
higher copper concentrations than patients without PCOS (P < 0.001). By contrast,
PCOS patients had lower serum calcium levels than patients without PCOS (P <
0.001). No significant differences were observed in the levels of serum zinc,
magnesium, and iron between PCOS and non-PCOS patients. PCOS patients with acne
had higher magnesium levels than those without acne (P = 0.020), and PCOS
patients with hirsutism had lower magnesium levels than those without hirsutism
(P = 0.037). High serum copper and low calcium levels may be correlated with
PCOS. Magnesium concentrations are correlated with acne and hirsutism in PCOS
patients. These results provide clues to explore the mechanism of PCOS and
guidance for element treatments in PCOS patients.
PMID- 27502955
TI - Scheduling rules to achieve lead-time targets in outpatient appointment systems.
AB - This paper considers how to schedule appointments for outpatients, for a clinic
that is subject to appointment lead-time targets for both new and returning
patients. We develop heuristic rules, which are the exact and relaxed appointment
scheduling rules, to schedule each new patient appointment (only) in light of
uncertainty about future arrivals. The scheduling rules entail two decisions.
First, the rules need to determine whether or not a patient's request can be
accepted; then, if the request is not rejected, the rules prescribe how to assign
the patient to an available slot. The intent of the scheduling rules is to
maximize the utilization of the planned resource (i.e., the physician staff), or
equivalently to maximize the number of patients that are admitted, while
maintaining the service targets on the median, the 95th percentile, and the
maximum appointment lead-times. We test the proposed scheduling rules with
numerical experiments using real data from the chosen clinic of Tan Tock Seng
hospital in Singapore. The results show the efficiency and the efficacy of the
scheduling rules, in terms of the service-target satisfaction and the resource
utilization. From the sensitivity analysis, we find that the performance of the
proposed scheduling rules is fairly robust to the specification of the
established lead-time targets.
PMID- 27502956
TI - The Quality and Accuracy of Mobile Apps to Prevent Driving After Drinking
Alcohol.
AB - BACKGROUND: Driving after the consumption of alcohol represents a significant
problem globally. Individual prevention countermeasures such as personalized
mobile app aimed at preventing such behavior are widespread, but there is little
research on their accuracy and evidence base. There has been no known assessment
investigating the quality of such apps. OBJECTIVE: This study aimed to determine
the quality and accuracy of apps for drink driving prevention by conducting a
review and evaluation of relevant mobile apps. METHODS: A systematic app search
was conducted following PRISMA guidelines. App quality was assessed using the
Mobile App Rating Scale (MARS). Apps providing blood alcohol calculators
(hereafter "calculators") were reviewed against current alcohol advice for
accuracy. RESULTS: A total of 58 apps (30 iOS and 28 Android) met inclusion
criteria and were included in the final analysis. Drink driving prevention apps
had significantly lower engagement and overall quality scores than alcohol
management apps. Most calculators provided conservative blood alcohol content
(BAC) time until sober calculations. None of the apps had been evaluated to
determine their efficacy in changing either drinking or driving behaviors.
CONCLUSIONS: This novel study demonstrates that most drink driving prevention
apps are not engaging and lack accuracy. They could be improved by increasing
engagement features, such as gamification. Further research should examine the
context and motivations for using apps to prevent driving after drinking in at
risk populations. Development of drink driving prevention apps should incorporate
evidence-based information and guidance, lacking in current apps.
PMID- 27502957
TI - Sensitivity of Image Features to Noise in Conventional and Respiratory-Gated
PET/CT Images of Lung Cancer: Uncorrelated Noise Effects.
AB - The effect of noise on image features has yet to be studied in depth. Our
objective was to explore how significantly image features are affected by the
addition of uncorrelated noise to an image. The signal-to-noise ratio and noise
power spectrum were calculated for a positron emission tomography/computed
tomography scanner using a Ge-68 phantom. The conventional and respiratory-gated
positron emission tomography/computed tomography images of 31 patients with lung
cancer were retrospectively examined. Multiple sets of noise images were created
for each original image by adding Gaussian noise of varying standard deviation
equal to 2.5%, 4.0%, and 6.0% of the maximum intensity for positron emission
tomography images and 10, 20, 50, 80, and 120 Hounsfield units for computed
tomography images. Image features were extracted from all images, and percentage
differences between the original image and the noise image feature values were
calculated. These features were then categorized according to the noise
sensitivity. The contour-dependent shape descriptors averaged below 4% difference
in positron emission tomography and below 13% difference in computed tomography
between noise and original images. Gray level size zone matrix features were the
most sensitive to uncorrelated noise exhibiting average differences >200% for
conventional and respiratory-gated images in computed tomography and 90% in
positron emission tomography. Image feature differences increased as the noise
level increased for shape, intensity, and gray-level co-occurrence matrix
features in positron emission tomography and for gray-level co-occurrence matrix
and gray-level size zone matrix features in conventional computed tomography.
Investigators should be aware of the noise effects on image features.
PMID- 27502958
TI - Adaptive Radiotherapy for Head and Neck Cancer.
AB - OBJECTIVE: To investigate the effects of adaptive radiotherapy on dosimetric,
clinical, and toxicity outcomes for patients with head and neck cancer undergoing
chemoradiotherapy with intensity-modulated radiotherapy. METHODS: Fifty-one
patients with advanced head and neck cancer underwent definitive
chemoradiotherapy with the original plan optimized to deliver 70.2 Gy. All
patients were resimulated at a median dose of 37.8 Gy (range, 27.0-48.6 Gy) due
to changes in tumor volume and/or patient weight loss (>15% from baseline).
Thirty-four patients underwent adaptive replanning for their boost planning (21.6
Gy). The dosimetric effects of the adaptive plan were compared to the original
plan and the original plan copied on rescan computed tomography. Acute and late
toxicities and tumor local control were assessed. Gross tumor volume reduction
rate was calculated. RESULTS: With adaptive replanning, the maximum dose to the
spinal cord, brain stem, mean ipsilateral, and contralateral parotid had a median
reduction of -4.5%, -3.0%, -6.2%, and -2.5%, respectively (median of 34
patients). Median gross tumor volume and boost planning target volume coverage
improved by 0.8% and 0.5%, respectively. With a median follow-up time of 17.6
months, median disease-free survival and overall survival was 14.8 and 21.1
months, respectively. Median tumor volume reduction rate was 35.2%. For patients
with tumor volume reduction rate <=35.2%, median disease-free survival was 8.7
months, whereas it was 16.9 months for tumor volume reduction rate >35.2%. Four
patients had residual disease after chemoradiotherapy, whereas 64.7% (20 of 34)
of patients achieved locoregional control. CONCLUSION: Implementation of adaptive
radiotherapy in head and neck cancer offers benefits including improvement in
tumor coverage and decrease in dose to organs at risk. The tumor volume reduction
rate during treatment was significantly correlated with disease-free survival and
overall survival.
PMID- 27502959
TI - Licoricidin, an isoflavonoid isolated from Glycyrrhiza uralensis Fisher, prevents
UVA-induced photoaging of human dermal fibroblasts.
AB - OBJECTIVE: Licoricidin is an isoflavonoid isolated from Glycyrrhiza uralensis
Fisher. In this study, we investigated the effects of licoricidin on photoaging
of UVA-irradiated human dermal fibroblasts (HDFs). METHODS: In vitro reactive
oxygen species (ROS) scavenging activity, cellular protective effect and
inhibition of elastase activity was determined by Fe3+ -EDTA/H2 O2 systems,
photohaemolysis and elastase activity assay, respectively. Anti-oxidative
capacity of the compound was evaluated by fluorescent ELISA and 2', 7'
dichlorofluorescin-diacetate (DCF-DA) assay. The expression of protein and
phosphorylation was examined using Western blot. RESULTS: The ROS scavenging
activity (OSC50 ) of licoricidin was 2.77 MUM. It was 3.1-fold higher than that
of L-ascorbic acid. Its protective effects were confirmed in a study of 1 O2
induced cellular damage to human erythrocytes. The tau50 value of 10 MUM of
licoricidin was 71.0 min; this was markedly higher than that obtained with alpha
tocopherol (37.0 min). The elastase inhibitory activity of licoricidin (IC50 of
61.2 MUM) was 2.1-fold more potent than that of oleanolic acid. Licoricidin
markedly reduced the UVA-induced intracellular ROS in a concentration-dependent
manner. Western blot revealed that licoricidin attenuated the UVA-dependent
induction of MMP-1 protein. Mechanistically, this appeared to be due to
licoricidin-dependent inhibition of mitogen-activated protein kinases (MAPK)
phosphorylation, which resulted in decreased c-Jun activation and reduced c-Jun
and c-Fos expression. CONCLUSION: Licoricidin blocks UVA-induced photoaging via
ROS scavenging. This activity converges to limit the activity of MMP-1. These
data suggest that licoricidin may be considered as an active ingredient in new
topically applied anti-ageing formulations.
PMID- 27502961
TI - Picturing a neuroanatomical vision in a cave.
PMID- 27502960
TI - Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency.
AB - Mitochondrial complex I (CI) deficiency is the most prevalent defect in the
respiratory chain in paediatric mitochondrial disease. This heterogeneous group
of diseases includes serious or fatal neurological presentations such as Leigh
syndrome and there are very limited evidence-based treatment options available.
Here we describe that cell membrane-permeable prodrugs of the complex II
substrate succinate increase ATP-linked mitochondrial respiration in CI-deficient
human blood cells, fibroblasts and heart fibres. Lactate accumulation in
platelets due to rotenone-induced CI inhibition is reversed and rotenone-induced
increase in lactate:pyruvate ratio in white blood cells is alleviated.
Metabolomic analyses demonstrate delivery and metabolism of [(13)C]succinate. In
Leigh syndrome patient fibroblasts, with a recessive NDUFS2 mutation, respiration
and spare respiratory capacity are increased by prodrug administration. We
conclude that prodrug-delivered succinate bypasses CI and supports electron
transport, membrane potential and ATP production. This strategy offers a
potential future therapy for metabolic decompensation due to mitochondrial CI
dysfunction.
PMID- 27502962
TI - Spinal cord, vertebral body, paraspinal muscle, and rib infarction: Tiny thrombus
detected by CT.
PMID- 27502963
TI - The magnetic apraxia of Denny-Brown.
PMID- 27502964
TI - Critically re-evaluating a common technique: Accuracy, reliability, and
confirmation bias of EMG.
PMID- 27502966
TI - Journal Club: Effect of comorbidity on mortality in multiple sclerosis.
PMID- 27502965
TI - Summary of comprehensive systematic review: Rehabilitation in multiple sclerosis:
Report of the Guideline Development, Dissemination, and Implementation
Subcommittee of the American Academy of Neurology.
PMID- 27502967
TI - Teaching NeuroImages: The syndrome of cutaneous photosensitivity, growth failure,
and basal ganglia calcification.
PMID- 27502968
TI - Teaching NeuroImages: Chronic sinus thrombosis with patency of occipital and
falcine cerebral venous sinuses.
PMID- 27502969
TI - Teaching Video NeuroImages: Thalamic infarct with pseudo-abducens and vertical
gaze palsies and an unusual stroke mechanism.
PMID- 27502970
TI - Methods for detecting, quantifying, and adjusting for dissemination bias in meta
analysis are described.
AB - OBJECTIVE: To systematically review methodological articles which focus on
nonpublication of studies and to describe methods of detecting and/or quantifying
and/or adjusting for dissemination in meta-analyses. To evaluate whether the
methods have been applied to an empirical data set for which one can be
reasonably confident that all studies conducted have been included. STUDY DESIGN
AND SETTING: We systematically searched Medline, the Cochrane Library, and Web of
Science, for methodological articles that describe at least one method of
detecting and/or quantifying and/or adjusting for dissemination bias in meta
analyses. RESULTS: The literature search retrieved 2,224 records, of which we
finally included 150 full-text articles. A great variety of methods to detect,
quantify, or adjust for dissemination bias were described. Methods included
graphical methods mainly based on funnel plot approaches, statistical methods,
such as regression tests, selection models, sensitivity analyses, and a great
number of more recent statistical approaches. Only few methods have been
validated in empirical evaluations using unpublished studies obtained from
regulators (Food and Drug Administration, European Medicines Agency). CONCLUSION:
We present an overview of existing methods to detect, quantify, or adjust for
dissemination bias. It remains difficult to advise which method should be used as
they are all limited and their validity has rarely been assessed. Therefore, a
thorough literature search remains crucial in systematic reviews, and further
steps to increase the availability of all research results need to be taken.
PMID- 27502972
TI - Epidemiology of hepatitis C virus and genotype distribution in immigrants
crossing to Europe from North and sub-Saharan Africa.
AB - BACKGROUND: The association between the prevalence of hepatitis C virus (HCV) and
immigration is rarely studied, particularly for the immigrants crossing to the
resettlement countries. Most of the published data are confined to those
immigrants who were resident in European countries and rarely immigrated before
they reach the final destination. Libya is a large country in North Africa with
the longest coast of the Mediterranean Sea facing the European Union. It has been
considered as the main transient station for African immigrants to Europe. The
objectives of this study were to determine: (1) the prevalence of HCV in African
immigrants gathered in Libya from different African countries on their way to
Europe and (2) HCV genotype distribution in these immigrants and its correlation
with different demographic factors. METHODS: A total of 14 205 serum samples were
collected in a 3-year period (2013-2015) from different immigrants from North and
sub-Saharan Africa who resided in the African immigrant campus, Tripoli, Libya.
The participants were interviewed, and relevant information was collected,
including socio-demographic, ethnic, and geographic variables. Each serum sample
was tested for anti-HCV antibody using ELISA. The genotypes were determined and
assigned using a specific genotyping assay and correlated with demographic and
potential risk factors of the recruited individuals. RESULTS: Of the immigrants
studied, 1078 (7.6%) were positive for HCV. The prevalence of HCV infection
ranged from 1.4% to 18.7%; it was higher among individuals arriving from Nile
river (3.6-18.7%) of North Africa, followed by those who arrived from the West
African region (2.1-14.1%), Horn of Africa (HOA, 6.8-9.9%), and Maghreb countries
(1.4-2.7%). The relative risk factor attributable to gender variation was not
significant (95% Cl: 0.8513-1.2381). Five genotypes were detected in 911 African
immigrants. Genotypic analysis showed that the predominant HCV genotypes in this
group were genotypes 4, 1, and 2 that accounted for 329 (36.1%), 326 (35.8%), and
131 (14.4%) strains, respectively, followed by genotype 3 that accounted for 87
(9.5%) strains. Genotype 5 was isolated mainly from 18 HOA (2%) and 20 West
African (2.2%) individuals. CONCLUSIONS: The prevalence of HCV is considered high
with a unique disparate distribution among African immigrants crossing to Europe.
This indicated that the prevalence of HCV is high among these immigrants and thus
may be reflected on the HCV prevalence in the guest countries. The broad genetic
heterogeneity of HCV genotypes detected here may impact the efficacy of
prevention and control efforts for HCV in both Europe and North and sub-Saharan
Africa; hence, an integrated global policy of actions is needed.
PMID- 27502971
TI - Conservation and divergence within the clathrin interactome of Trypanosoma cruzi.
AB - Trypanosomatids are parasitic protozoa with a significant burden on human health.
African and American trypanosomes are causative agents of Nagana and Chagas
disease respectively, and speciated about 300 million years ago. These parasites
have highly distinct life cycles, pathologies, transmission strategies and
surface proteomes, being dominated by the variant surface glycoprotein (African)
or mucins (American) respectively. In African trypanosomes clathrin-mediated
trafficking is responsible for endocytosis and post-Golgi transport, with several
mechanistic aspects distinct from higher organisms. Using clathrin light chain
(TcCLC) and EpsinR (TcEpsinR) as affinity handles, we identified candidate
clathrin-associated proteins (CAPs) in Trypanosoma cruzi; the cohort includes
orthologs of many proteins known to mediate vesicle trafficking, but
significantly not the AP-2 adaptor complex. Several trypanosome-specific proteins
common with African trypanosomes, were also identified. Fluorescence microscopy
revealed localisations for TcEpsinR, TcCLC and TcCHC at the posterior region of
trypomastigote cells, coincident with the flagellar pocket and Golgi apparatus.
These data provide the first systematic analysis of clathrin-mediated trafficking
in T. cruzi, allowing comparison between protein cohorts and other trypanosomes
and also suggest that clathrin trafficking in at least some life stages of T.
cruzi may be AP-2-independent.
PMID- 27502973
TI - Changes in choroidal thickness after intraocular pressure reduction following
trabeculectomy.
PMID- 27502975
TI - Severe Sarcoidosis Phenotypes: An Occupational Hazard?
PMID- 27502974
TI - A dynamical framework to relate perceptual variability with multisensory
information processing.
AB - Multisensory processing involves participation of individual sensory streams,
e.g., vision, audition to facilitate perception of environmental stimuli. An
experimental realization of the underlying complexity is captured by the "McGurk
effect"- incongruent auditory and visual vocalization stimuli eliciting
perception of illusory speech sounds. Further studies have established that time
delay between onset of auditory and visual signals (AV lag) and perturbations in
the unisensory streams are key variables that modulate perception. However, as of
now only few quantitative theoretical frameworks have been proposed to understand
the interplay among these psychophysical variables or the neural systems level
interactions that govern perceptual variability. Here, we propose a dynamic
systems model consisting of the basic ingredients of any multisensory processing,
two unisensory and one multisensory sub-system (nodes) as reported by several
researchers. The nodes are connected such that biophysically inspired coupling
parameters and time delays become key parameters of this network. We observed
that zero AV lag results in maximum synchronization of constituent nodes and the
degree of synchronization decreases when we have non-zero lags. The attractor
states of this network can thus be interpreted as the facilitator for stabilizing
specific perceptual experience. Thereby, the dynamic model presents a
quantitative framework for understanding multisensory information processing.
PMID- 27502976
TI - 16 Years and Counting? Time to Implement Noninvasive Screening for ARDS.
PMID- 27502977
TI - Toward Personalized Prescription of Systemic Steroids for Patients Hospitalized
With COPD Exacerbations.
PMID- 27502978
TI - Could Cryo-Biopsies Lead Bronchoscopy Into the Ice Age?
PMID- 27502981
TI - Considerations for the Interpretation of the Results Described in "Analysis of
National Trends in Admissions for Pulmonary Embolism".
PMID- 27502982
TI - Is FGF23 or FGF21 a Promising Biomarker to Indicate the Aging Process in COPD?
PMID- 27502983
TI - Hospitals' Patterns of Noninvasive Ventilation in Asthma: Evidence or Deep
Recommendations Needed?
PMID- 27502984
TI - Response.
PMID- 27502985
TI - Comparison of the Accuracy of Nurse-Performed and Physician-Performed Lung
Ultrasound in the Diagnosis of Cardiogenic Dyspnea.
PMID- 27502986
TI - Normoxic Recovery Reverses Intermittent Hypoxia-Induced Systemic and Vascular
Inflammation.
PMID- 27502987
TI - Serum Surfactant Protein D as a Marker of Asthma Severity.
PMID- 27502988
TI - Response.
PMID- 27502989
TI - Sirolimus Therapy for Patients With Lymphangioleiomyomatosis Leads to Loss of
Chylous Ascites and Circulating LAM Cells.
AB - A young woman received a diagnosis of abdominal, sporadic
lymphangioleiomyomatosis (LAM) and multiple abdominal lymphangioleiomyomas and
was referred for recurrent chylous ascites responding only to a fat-free diet. On
admission, pulmonary function test (PFT) results showed a moderate reduction in
the transfer factor for carbon monoxide with normal exercise performance. The
serum vascular endothelial growth factor D (VEGF-D) level was 2,209 pg/mL. DNA
sequences, amplified at loci kg8, D16S3395, D16S3024, D16S521, and D16S291 on
chromosome 16p13.3, showed a loss of heterozygosity (LOH) only for kg8. Fat-free
total parenteral nutrition in association with sirolimus (2 mg po daily) was
initiated. Serum sirolimus levels were maintained at concentrations between 5 and
15 ng/mL. After 1 month, reintroduction of a low-fat oral feeding was achieved
without recurrence of ascites. PFT results were stable. Interestingly, clinical
improvement was associated with a reduction in the VEGF-D serum level (1,558
pg/mL). LOH at the kg8 biomarker in blood LAM cells was no longer detected.
PMID- 27502990
TI - A 56-Year-Old Woman With a Recurrent Pleural Effusion After Chest Trauma.
PMID- 27502991
TI - "Code Blue" in a 66-Year-Old Man in the Cardiology Department.
PMID- 27502992
TI - A 57-Year-Old Man With Insidious Dyspnea and Nonpleuritic Chest and Back Pain.
AB - A 57-year-old man with a history of DVT and pulmonary embolism, transient
ischemic attacks, prior 60 pack-year smoking history, and oxygen-dependent COPD
presented with insidiously worsening dyspnea associated with new pleuritic chest
and back pain.
PMID- 27502993
TI - A 44-Year-Old Man With Sore Throat and Fatigue After Using an Old Camper Van.
AB - A 44-year-old man from Connecticut with no significant past medical history
presented to the ED with a 2-week history of sore throat and fatigue,
subsequently developing cough, dyspnea, fevers, and chills. The patient reported
buying an old camper van and noticed a large infestation of rodent droppings,
which he had cleaned thoroughly from the cabin. He used the camper van on several
camping trips in Vermont, and symptoms started on his return.
PMID- 27502994
TI - A 29-Year-Old Woman With Severe Sepsis and Hemoptysis.
AB - A 29-year-old woman presented with a 1-week history of fever, weakness, anorexia,
darkened urine, and mild cough. The patient described her cough as nonproductive
and without hemoptysis. She had no chest pain. The patient's medical history was
significant for x-linked hypophosphatemia, renal stones, migraine headaches, and
chronic back pain managed on prescribed oral opiates for some time. She reported
regular cigarette smoking, but denied illicit or IV drug use or any recent travel
or sick contacts. The patient also had no known pertinent family history.
PMID- 27502995
TI - A 51-Year-Old Woman With Hypoacusia and Increased Respiratory Effort in the
Supine Position and OSA.
AB - A 51-year-old woman with a personal history of vitiligo, normal thyroid hormone
studies, a simple hysterectomy for multiple uterine myomas at age 35 years, and
childhood adenotonsillectomy was seen for progressive hearing loss. She reported
mild asthenia, cold intolerance, mild dysphagia with frequent choking while
eating and drinking, and a progressive increase in inspiratory effort, especially
in the supine position. Her partner described a progressively worsening history
of snoring and witnessed apneic episodes, mostly in the supine position. Mild to
moderate daytime sleepiness was also present.
PMID- 27502996
TI - 2017 Clinical trials update in new treatments of beta-thalassemia.
AB - The underlying basis of beta-thalassemia pathology is the diminished beta-globin
synthesis leading to alpha-globin accumulation and premature apoptotic
destruction of erythroblasts, causing oxidative stress-induced ineffective
erythropoiesis, bone marrow hyperplasia, splenomegaly, and increased intestinal
iron absorption with progressive iron overload. Better understanding of the
molecular mechanisms underlying this disease led to the recognition of new
targets with potential therapeutic utility. Agents such as JAK2 inhibitors and
TGF-beta ligand traps that reduce the ineffective erythropoiesis process are
already being tested in clinical trials with promising results. Other agents that
aim to reduce oxidative stress (activators of Foxo3, HRI-eIF2aP, Prx2, Hsp70, and
PK anti-oxidant systems and inhibitors of HO-1) and to decrease iron overload
(hepcidin agonists, erythroferrone inhibitors and exogenous transferrin) are also
under experimental investigation. Significant progress has also been made in the
area of allogeneic hematopoietic stem cell transplantation with several ongoing
clinical trials examining new condition regimens as well as different donor
selection and stem cell source options. Gene therapy has reached a critical point
and phase 1 clinical trials have recently been launched to examine the
effectiveness and especially long term safety. Epigenetic manipulation and
genomic editing of the gamma- or beta-globin gene are novel and promising
experimental gene therapy approaches for beta-thalassemia giving hope for cure
for this chronic disease. This review outlines the key points of the molecular
mechanisms underlying beta-thalassemia in relation to the development of new
therapies and an update is given both at the pre-clinical and clinical level. Am.
J. Hematol. 91:1135-1145, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27502997
TI - Borophene as an extremely high capacity electrode material for Li-ion and Na-ion
batteries.
AB - "Two-dimensional (2D) materials as electrodes" is believed to be the trend for
future Li-ion and Na-ion battery technologies. Here, by using first-principles
methods, we predict that the recently reported borophene (2D boron sheets) can
serve as an ideal electrode material with high electrochemical performance for
both Li-ion and Na-ion batteries. The calculations are performed on two
experimentally stable borophene structures, namely beta12 and chi3 structures.
The optimized Li and Na adsorption sites are identified, and the host materials
are found to maintain good electric conductivity before and after adsorption.
Besides advantages including small diffusion barriers and low average open
circuit voltages, most remarkably, the storage capacity can be as high as 1984 mA
h g(-1) in beta12 borophene and 1240 mA h g(-1) in chi3 borophene for both Li and
Na, which are several times higher than the commercial graphite electrode and are
the highest among all the 2D materials discovered to date. Our results highly
support that borophenes can be appealing anode materials for both Li-ion and Na
ion batteries with extremely high power density.
PMID- 27502998
TI - Electronic properties of highly-active Ag3AsO4 photocatalyst and its band gap
modulation: an insight from hybrid-density functional calculations.
AB - The electronic structures of highly active Ag-based oxide photocatalysts Ag3AsO4
and Ag3PO4 are studied by hybrid-density functional calculations. It is revealed
that Ag3AsO4 and Ag3PO4 are indirect band gap semiconductors. The Hartree-Fock
mixing parameters are fitted for experimental band gaps of Ag3AsO4 (1.88 eV) and
Ag3PO4 (2.43 eV). The smaller electron effective mass and the lower valence band
edge of Ag3AsO4 are likely to be responsible for the superior photocatalytic
oxidation reaction to Ag3PO4. The comparable lattice constant and analogous
crystal structure between the two materials allow the opportunities of fine
tuning the band gap of Ag3AsxP1-xO4 using a solid-solution approach. The
development of Ag3AsxP1-xO4 should be promising for the discovery of novel
visible-light sensitized photocatalysts.
PMID- 27502999
TI - Negative Capacitance in BaTiO3/BiFeO3 Bilayer Capacitors.
AB - Negative capacitances provide an approach to reduce heat generations in field
effect transistors during the switch processes, which contributes to further
miniaturization of the conventional integrated circuits. Although there are many
studies about negative capacitances using ferroelectric materials, the direct
observation of stable ferroelectric negative capacitances has rarely been
reported. Here, we put forward a dc bias assistant model in bilayer capacitors,
where one ferroelectric layer with large dielectric constant and the other
ferroelectric layer with small dielectric constant are needed. Negative
capacitances can be obtained when external dc bias electric fields are larger
than a critical value. Based on the model, BaTiO3/BiFeO3 bilayer capacitors are
chosen as study objects, and negative capacitances are observed directly.
Additionally, the upward self-polarization effect in the ferroelectric layer
reduces the critical electric field, which may provide a method for realizing
zero and/or small dc bias assistant negative capacitances.
PMID- 27503000
TI - Comparison and combination of blood DNA methylation at smoking-associated genes
and at lung cancer-related genes in prediction of lung cancer mortality.
AB - Epigenome-wide association studies have established methylation patterns related
to smoking, the major risk factor of lung cancer (LC), which are distinct from
methylation profiles disclosed in LC patients. This study simultaneously
investigated associations of smoking-associated and LC-related methylation
markers with LC mortality. DNA methylation was determined by HM450K assay in
baseline blood samples of 1,565 older adults in a population-based case-cohort
study. The associations of 151 smoking-associated CpGs (smoCpGs) and 3,806 LC
related CpGs (caCpGs) with LC mortality were assessed by weighted Cox regression
models, controlling for potential confounders. Multi-loci methylation scores were
separately constructed based on smoCpGs and caCpGs. During a median follow-up of
13.8 years, 60 participants who had a first diagnosis of LC died from LC. The
average time between sample collection and LC diagnosis was 5.8 years.
Hypomethylation at 77 smoCpGs and 121 caCpGs, and hypermethylation at 4 smoCpGs
and 66 caCpGs were associated with LC mortality. The associations were much
stronger for smoCpGs than for caCpGs. Hazard ratios (95% CI) were 7.82 (2.91
21.00) and 2.27 (0.75-6.85), respectively, for participants in highest quartile
of Score I (based on 81 smoCpGs) and Score II (based on 187 caCpGs), compared
with participants in the corresponding lower three quartiles. Score I
outperformed Score II, with an optimism-corrected C-index of 0.87 vs. 0.77. In
conclusion, although methylation changes of both smoking-associated and LC
related genes are associated with LC mortality, only smoking-associated
methylation markers predict LC mortality with high accuracy, and may thus serve
as promising candidates to identify high risk populations for LC screening.
PMID- 27503001
TI - Comparison of neuropsychological and functional outcomes in Alzheimer's disease
patients with good or bad response to a cognitive stimulation treatment: a
retrospective analysis.
AB - BACKGROUND: The benefit of cognitive stimulation (CS) treatments in dementia is
unequal. This study has sought to identify cognitive and functional measurements
before and after the treatment which are indicative of a better response to a one
year CS program. METHODS: A retrospective observational study was conducted
between 2004 and 2012 in a sample of 60 users diagnosed with mild Alzheimer's
disease (AD) who followed a one-year CS program and underwent a cognitive and
functional assessment before and after the intervention. As a primary measure of
treatment response, we used the annual change of the Mini-Mental State
Examination (MMSE) scores, which distinguished good responders (R) from non
responders (NR). RESULTS: 51.7% of patients classified as R at baseline had a
higher cognitive performance in attention, immediate verbal memory, language, and
working memory compared to NR. No initial statistically significant differences
were found between R and NR in any sociodemographic variables, medical
conditions, anxiety and/or depressive symptoms, treatment with cholinesterase
inhibitors (ChEIs), level of insight, global cognitive function (MMSE), or
functional capacity. After 12 months of treatment, R had significantly better
results than NR on MMSE, temporal orientation, category evocation, and
Philadelphia Geriatric Center-Instrumental Activities of Daily Living (PGC-IADL).
CONCLUSION: The response to a CS treatment of some subjects over others is linked
to cognitive and functional capacity. This research contributes to characterize
the neuropsychological profile that differentiates subjects who respond better
than others before and after the treatment. This should contribute to customize
and optimize neuropsychological interventions in patients with AD.
PMID- 27503002
TI - Electron acceptor redox potential globally regulates transcriptomic profiling in
Shewanella decolorationis S12.
AB - Electron acceptor redox potential (EARP) was presumed to be a determining factor
for microbial metabolism in many natural and engineered processes. However,
little is known about the potentially global effects of EARP on bacteria. In this
study, we compared the physiological and transcriptomic properties of Shewanella
decolorationis S12 respiring with different EARPs in microbial electrochemical
systems to avoid the effects caused by the other physicochemical properties of
real electron acceptor. Results showed that the metabolic activities of strain
S12 were nonlinear responses to EARP. The tricarboxylic acid cycle for central
carbon metabolism was down-regulated while glyoxylate shunt was up-regulated at
0.8 V compared to 0.2 and -0.2 V, which suggested that EARP is an important but
not the only determinant for metabolic pathways of strain S12. Moreover, few
cytochrome c genes were differentially expressed at different EARPs. The energy
intensive flagella assembly and assimilatory sulfur metabolism pathways were
significantly enriched at 0.8 V, which suggested strain S12 had stronger
electrokinesis behavior and oxidative stress-response at high EARP. This study
provides the first global information of EARP regulations on microbial
metabolism, which will be helpful for understanding microorganism respiration.
PMID- 27503003
TI - Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing
of Pseudomonas aeruginosa.
AB - Bacteria have evolved multiple strategies for causing infections that include
producing virulence factors, undertaking motility, developing biofilms, and
invading host cells. N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS)
tightly regulates the expression of multiple virulence factors in the
opportunistic pathogenic bacterium Pseudomonas aeruginosa. Thus, inhibiting QS
could lead to health benefits. In this study, we demonstrate an anti-virulence
activity of a cranberry extract rich in proanthocyanidins (cerPAC) against P.
aeruginosa in the model host Drosophila melanogaster and show this is mediated by
QS interference. cerPAC reduced the production of QS-regulated virulence
determinants and protected D. melanogaster from fatal infection by P. aeruginosa
PA14. Quantification of AHL production using liquid chromatography-mass
spectrometry confirmed that cerPAC effectively reduced the level of AHLs produced
by the bacteria. Furthermore, monitoring QS signaling gene expression revealed
that AHL synthases LasI/RhlI and QS transcriptional regulators LasR/RhlR genes
were inhibited and antagonized, respectively, by cerPAC. Molecular docking
studies suggest that cranberry-derived proanthocyanidin binds to QS
transcriptional regulators, mainly interacting with their ligand binding sites.
These findings provide insights into the underlying mechanisms of action of a
cerPAC to restrict the virulence of P. aeruginosa and can have implications in
the development of alternative approaches to control infections.
PMID- 27503004
TI - Women's birth place preferences in the United Kingdom: a systematic review and
narrative synthesis of the quantitative literature.
AB - BACKGROUND: Current clinical guidelines and national policy in England support
offering 'low risk' women a choice of birth setting, but despite an increase in
provison of midwifery units in England the vast majority of women still give
birth in obstetric units and there is uncertainty around how best to configure
services. There is therefore a need to better understand women's birth place
preferences. The aim of this review was to summarise the recent quantitative
evidence on UK women's birth place preferences with a focus on identifying the
service attributes that 'low risk' women prefer and on identifying which
attributes women prioritise when choosing their intended maternity unit or birth
setting. METHODS: We searched Medline, Embase, PsycINFO, Science Citation Index,
Social Science Index, CINAHL and ASSIA to identify quantitative studies published
in scientific journals since 1992 and designed to describe and explore women's
preferences in relation to place of birth. We included experimental stated
preference studies, surveys and mixed-methods studies containing relevant
quantitative data, where participants were 'low risk' or 'unselected' groups of
women with experience of UK maternity services. RESULTS: We included five
experimental stated preference studies and four observational surveys, including
a total of 4201 respondents. Most studies were old with only three conducted
since 2000. Methodological quality was generally poor. The attributes and
preferences most commonly explored related to pain relief, continuity of midwife,
involvement/availability of medical staff, 'homely' environment/atmosphere,
decision-making style, distance/travel time and need for transfer. Service
attributes that were almost universally valued by women included local services,
being attended by a known midwife and a preference for a degree of control and
involvement in decision-making. A substantial proportion of women had a strong
preference for care in a hospital setting where medical staff are not necessarily
involved in their care, but are readily available. CONCLUSIONS: The majority of
women appear to value some service attributes while preferences differ for
others. Policy makers, commissioners and service providers might usefully
consider how to extend the availability of services that most women value while
offering a choice of options that enable women to access services that best fit
their needs and preferences.
PMID- 27503005
TI - mTOR Inhibitors in Castration-Resistant Prostate Cancer: A Systematic Review.
AB - BACKGROUND: The progression of prostate cancer to castration-resistant prostate
cancer (CRPC) is often a result of somatic alterations in the PI3K/Akt/mTOR
(mammalian target of rapamycin) pathway, suggesting that therapies targeting this
pathway might lead to improved survival and efficacy. Here, we systematically
evaluate the results of clinical trials investigating mTOR inhibition in CRPC and
utilize preclinical data to predict clinical outcomes. METHODS: Trials included
in the study were identified through PubMed and via review of conference
abstracts cited by relevant review articles. The eligibility of trials was
independent of sample size, clinical setting, or date. RESULTS: A total of 14
studies were eligible for qualitative analysis. The clinical setting was variable
among studies, and all utilized an allosteric mTOR inhibitor as either a
monotherapy or in combination. Molecular criteria were evaluated in three trials.
Among most studies, the prostate-specific antigen level declined during
treatment, but often increased shortly thereafter. Partial responses to treatment
were minimal, and no complete responses were reported. Two studies exploring
therapy with an mTOR inhibitor in combination with bicalutamide resulted in
minimal efficacy. Overall, allosteric mTOR inhibition was deemed to be inadequate
for the treatment of CRPC. CONCLUSION: Preclinical data suggest that a reciprocal
feedback mechanism between PI3K and androgen receptor signaling is a potential
mechanism behind the clinical inefficacy of mTOR inhibitors in CRPC, indicating
combinatorial targeting of PI3K, mTORC1/2, and the androgen receptor might be
more effective. Comprehensive analysis of preclinical data to assess clinical
trial targets and efficacy may reduce the number of unproductive trials and
identify potentially beneficial combinatorial therapies for resistant disease.
PMID- 27503006
TI - Impact of Diabetes on Outcomes of Sorafenib Therapy for Hepatocellular Carcinoma.
AB - BACKGROUND: Patients with diabetes are at increased risk of developing
hepatocellular carcinoma (HCC) and have a poorer prognosis as compared to non
diabetics when HCC occurs. Diabetics with non-HCC cancers are at higher risk of
toxicity related to systemic therapy, but data on HCC are lacking. OBJECTIVE: The
aim of this study was to evaluate safety and effectiveness of sorafenib in HCC
patients according to the presence/absence of diabetes. PATIENTS AND METHODS:
From October 2008 to June 2014, 313 patients with HCC treated with sorafenib were
enrolled. The patients were staged according to the BCLC system. Treatment
response was evaluated according to the mRECIST criteria. The main evaluated
outcomes were the overall survival and the safety in the two groups. RESULTS:
Patients were divided in two groups: 80 diabetics (DIAB) and 233 nondiabetics
(nDIAB). The median treatment duration was 4 months in DIAB and 3 months in
nDIAB. Main adverse events occurred with comparable frequency in both groups,
with the exception of rash, that was more frequent among DIAB than in nDIAB: 27.5
% vs 17.6 % (P = .047). The median overall survival was 9 months in nDIAB and 10
months in DIAB group (P = .535). Median time-to-progression (TTP) was longer the
in DIAB than the nDIAB group (P = .038). CONCLUSIONS: Sorafenib was as safe as
effective in DIAB and in nDIAB patients. The longer TTP observed among DIAB than
in nDIAB patients might suggest a better anticancer effect of sorafenib in
patients with diabetes.
PMID- 27503007
TI - Motor priming in virtual reality can augment motor-imagery training efficacy in
restorative brain-computer interaction: a within-subject analysis.
AB - BACKGROUND: The use of Brain-Computer Interface (BCI) technology in
neurorehabilitation provides new strategies to overcome stroke-related motor
limitations. Recent studies demonstrated the brain's capacity for functional and
structural plasticity through BCI. However, it is not fully clear how we can take
full advantage of the neurobiological mechanisms underlying recovery and how to
maximize restoration through BCI. In this study we investigate the role of
multimodal virtual reality (VR) simulations and motor priming (MP) in an upper
limb motor-imagery BCI task in order to maximize the engagement of sensory-motor
networks in a broad range of patients who can benefit from virtual rehabilitation
training. METHODS: In order to investigate how different BCI paradigms impact
brain activation, we designed 3 experimental conditions in a within-subject
design, including an immersive Multimodal Virtual Reality with Motor Priming
(VRMP) condition where users had to perform motor-execution before BCI training,
an immersive Multimodal VR condition, and a control condition with standard 2D
feedback. Further, these were also compared to overt motor-execution. Finally, a
set of questionnaires were used to gather subjective data on Workload,
Kinesthetic Imagery and Presence. RESULTS: Our findings show increased capacity
to modulate and enhance brain activity patterns in all extracted EEG rhythms
matching more closely those present during motor-execution and also a strong
relationship between electrophysiological data and subjective experience.
CONCLUSIONS: Our data suggest that both VR and particularly MP can enhance the
activation of brain patterns present during overt motor-execution. Further, we
show changes in the interhemispheric EEG balance, which might play an important
role in the promotion of neural activation and neuroplastic changes in stroke
patients in a motor-imagery neurofeedback paradigm. In addition,
electrophysiological correlates of psychophysiological responses provide us with
valuable information about the motor and affective state of the user that has the
potential to be used to predict MI-BCI training outcome based on user's profile.
Finally, we propose a BCI paradigm in VR, which gives the possibility of motor
priming for patients with low level of motor control.
PMID- 27503008
TI - Fragile X mental retardation protein knockdown in the developing Xenopus tadpole
optic tectum results in enhanced feedforward inhibition and behavioral deficits.
AB - BACKGROUND: Fragile X Syndrome is the leading monogenetic cause of autism and
most common form of intellectual disability. Previous studies have implicated
changes in dendritic spine architecture as the primary result of loss of Fragile
X Mental Retardation Protein (FMRP), but recent work has shown that neural
proliferation is decreased and cell death is increased with either loss of FMRP
or overexpression of FMRP. The purpose of this study was to investigate the
effects of loss of FMRP on behavior and cellular activity. METHODS: We knocked
down FMRP expression using morpholino oligos in the optic tectum of Xenopus
laevis tadpoles and performed a series of behavioral and electrophysiological
assays. We investigated visually guided collision avoidance, schooling, and
seizure propensity. Using single cell electrophysiology, we assessed intrinsic
excitability and synaptic connectivity of tectal neurons. RESULTS: We found that
FMRP knockdown results in decreased swimming speed, reduced schooling behavior
and decreased seizure severity. In single cells, we found increased inhibition
relative to excitation in response to sensory input. CONCLUSIONS: Our results
indicate that the electrophysiological development of single cells in the absence
of FMRP is largely unaffected despite the large neural proliferation defect. The
changes in behavior are consistent with an increase in inhibition, which could be
due to either changes in cell number or altered inhibitory drive, and indicate
that FMRP can play a significant role in neural development much earlier than
previously thought.
PMID- 27503009
TI - Models of wound healing: an emphasis on clinical studies.
AB - BACKGROUND: The healing of wounds has always provided challenges for the medical
community whether chronic or acute. Understanding the processes which enable
wounds to heal is primarily carried out by the use of models, in vitro, animal
and human. It is generally accepted that the use of human models offers the best
opportunity to understand the factors that influence wound healing as well as to
evaluate efficacy of treatments applied to wounds. OBJECTIVES: The objective of
this article is to provide an overview of the different methodologies that are
currently used to experimentally induce wounds of various depths in human
volunteers and examines the information that may be gained from them. METHODS:
There is a number of human volunteer healing models available varying in their
invasiveness to reflect the different possible depth levels of wounds. RESULTS:
Currently available wound healing models include sequential tape stripping,
suction blister, abrasion, laser, dermatome, and biopsy techniques. The various
techniques can be utilized to induce wounds of variable depth, from removing
solely the stratum corneum barrier, the epidermis to even split-thickness or full
thickness wounds. CONCLUSION: Depending on the study objective, a number of
models exist to study wound healing in humans. These models provide efficient and
reliable results to evaluate treatment modalities.
PMID- 27503010
TI - Reconstruct the proximal radius with iliac graft and elastic intramedullary nail
fixation after tumor resection.
AB - BACKGROUND: This study aims to introduce a novel technique in treating benign
bone tumors of the proximal radius by elastic intramedullary nail fixation and
iliac graft after tumor resection. METHOD: In this retrospective case series, the
treatment outcomes of 17 patients with benign bone tumor involving the proximal
radius were reported from January 2010 to August 2014. All the patients received
reconstruction surgery with iliac graft and elastic intramedullary nail fixation
after tumor resection. Pain scoring was assessed using the 0 to 10 numerical
rating scale. The quality of life scoring was assessed using the SF-30 scoring
system. In addition, functional outcome was assessed with the Musculoskeletal
Tumor Society score and the Disabilities of the Arm, Shoulder, and Hand score.
RESULTS: The mean follow-up was 16 months (range, 10-22). The average bone
consolidate time was 19.2 weeks (range, 16-24 weeks). The pre- and postoperative
pain scores were 5.47 +/- 1.58 and 1.18 +/- 0.39, respectively. The pain symptom
was significantly ameliorated after the operation (t = 13.50, p < 0.01). The pre-
and postoperative and the quality of life scores were 48.29 +/- 6.58 and 77.47 +/
5.89, respectively; the quality of life score was dramatically improved (t =
20.11, p < 0.01). The mean Musculoskeletal Tumor Society score was 83.41 %
(range, 63-93 %) and the mean Disabilities of the Arm, Shoulder, and Hand score
was 14.1 (range, 5.8-38.3). CONCLUSION: Taken together, the application of iliac
graft and elastic intramedullary nail fixation after excision of lesions might be
associated to a significant reduction of the pain and improvement of QOL (quality
of life) and limb function of patients with benign bone tumors of proximal
radius.
PMID- 27503011
TI - The New Era of Organ Transplantation in China.
PMID- 27503013
TI - Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic
Dilated Cardiomyopathy.
AB - BACKGROUND: Current risk stratification of idiopathic dilated cardiomyopathy
(IDC) lacks sufficient sensitivity and specificity. The objective of this study
was to investigate the predictive role of frontal QRS-T angles in IDC. METHODS: A
prospective study with 509 IDC patients was performed from February 2008 to
December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of
Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up
was conducted every 6 months. Analyses by Cox Proportional Hazards model were
performed to evaluate the association between QRS-T angle and outcomes. The
primary outcome of interest was all-cause mortality. RESULTS: During a median
follow-up of 34 months, 90 of 316 patients with QRS-T angles >90 degrees died
compared to 31 of 193 patients with QRS-T angles <=90 degrees (hazard ratio [HR]
=2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T
angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR =
2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T
angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05),
cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR
= 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T
angle (100.9 +/- 53.4 degrees vs. 107.2 +/- 54.4 degrees , P < 0.001). The
frontal QRS-T angle correlated well with established risk factors, such as left
ventricular ejection fraction, brain natriuretic peptide, and New York Heart
Association functional class. CONCLUSIONS: The frontal QRS-T angle is a powerful
predictor of all-cause mortality, cardiac mortality, and worsening heart failure
in IDC patients, independent of well-established prognostic factors. Optimized
therapy significantly narrows the QRS-T angle, which might be an indicator of
medication compliance, but this requires further investigation.
PMID- 27503014
TI - Is There a Reliable Method to Predict the Limb Length Discrepancy after
Chemotherapy and Limb Salvage Surgery in Children with Osteosarcoma?
AB - BACKGROUND: For a child with osteosarcoma, prediction of the limb length
discrepancy at maturity is important when planning for limb salvage surgery. The
purpose of this study was to provide a reliable prediction method. METHODS: A
retrospective review of Chinese children receiving chemotherapy for osteosarcoma
before skeletal maturity was conducted. Standing full-length radiographs of the
lower extremity were used for length measurements. Length-for-age curves were
constructed using the LMS method. The lower limb multiplier for a specific age
and gender was calculated using the formula M = Lm/L, where M was the gender- and
age-specific multiplier, Lmwas the bone length at maturity, and L was the age
specific bone length. Prematurity and postmaturity radiographs were used to
assess the accuracy of the prediction methods. RESULTS: A total of 513
radiographs of 131 boys and 314 radiographs of 86 girls were used to calculate
the coefficients of the multiplier. The multipliers of 8-, 9-, 10-, 11-, 12-, 13
, 14-, 15-, 16-, 17-, and 18-year-old boys after chemotherapy for osteosarcoma
were 1.394, 1.306, 1.231, 1.170, 1.119, 1.071, 1.032, 1.010, 1.004, 1.001, and
1.000, respectively; while for girls at the same ages, the multipliers were
1.311, 1.221, 1.146, 1.092, 1.049, 1.021, 1.006, 1.001, 1.000, 1.000, and 1.000,
respectively. Prematurity and postmaturity femoral and tibial lengths of 21
patients were used to assess the prediction accuracy. The mean prediction error
was 0 cm, 0.8 cm, and 1.6 cm for the multiplier method using our coefficients,
Paley's coefficients, and Anderson's method, respectively. CONCLUSIONS: Our
coefficients for the multiplier method are reliable in predicting lower limb
length growth of Chinese children with osteosarcoma.
PMID- 27503012
TI - Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A
Nephropathy: A Randomized Controlled Trial.
AB - BACKGROUND: The efficacy and safety of telmisartan combined with clopidogrel,
leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear.
This study was designed to evaluate the efficacy and safety of telmisartan
combined with clopidogrel, leflunomide, or both drugs for IgAN. METHODS: It is a
multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN
patients were recruited in 13 renal units across Beijing, China, from July 2010
to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients
continuing on 80 mg/d telmisartan were randomly assigned to additionally receive
placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C),
or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week
intervention was completed by 360 patients. The primary endpoint was change in 24
h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the
changes at 4, 12, and 24 weeks. Generalized estimating equations were used to
evaluate changes in hematuria grade. This trial was registered at the Chinese
Clinical Trial Registry. RESULTS: The effects of telmisartan combined with
leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18
0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44-96.49] MUmol/L, P
< 0.001), in serum creatinine (9.49 [95% CI 6.54-12.44] MUmol/L, P < 0.001), and
in estimated glomerular filtration rate (-6.72 [95% CI-9.46 to -3.98] ml.min
1.1.73 m-2, P < 0.001) were statistically significant, whereas they were not
statistically significant on changes in systolic and diastolic blood pressure and
weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical
effect on any outcome, and there was no interaction between the interventions. No
obvious adverse reactions were observed. CONCLUSIONS: Telmisartan combined with
leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in
certain IgAN patients. TRIAL REGISTRATION: chictr.org.cn, ChiCTR-TRC-10000776;
http://www.chictr.org.cn/showproj.aspx?proj=8760.
PMID- 27503015
TI - Inserting the Ulnar Prosthesis into Radius as a Novel Salvage Surgery for
Revision Total Elbow Arthroplasty with Massive Bone Defect.
AB - BACKGROUND: Infection and aseptic loosening are common complications of total
elbow arthroplasty (TEA) and often require revision surgery. However, bone
defects, along with other complications, bring an extra difficulty to the second
surgery, especially for patients with a massive bone defect in the proximal ulna.
Several methods including allograft or autograft have been introduced into
practice, but none sufficiently solves these problems. METHODS: We conducted a
new surgical method for patients with a massive ulnar bone defect needing
revision TEA. During revision arthroplasty, the ulnar prosthesis was inserted
into the radius as a salvage procedure. Four consecutive patients received
revision arthroplasty with this method between 2013 and 2016. Patients' data were
collected to evaluate the clinical outcome. RESULTS: All patients had a Grade III
ulnar bone defect. At the last follow-up session, all patients reported a
painless, functional elbow joint. Three patients suffered from a periprosthetic
infection that was completely cured using the two-stage method. No major
complications, including infection, aseptic loosening, or wound problems were
found. One patient had a transient ulnar neuritis, and another had a transient
radial neuritis. Both patients had full recovery at the last follow-up session.
CONCLUSIONS: Inserting an ulnar prosthesis into the radius is a novel procedure
for patients with a massive bone defect due to infection or aseptic loosening. It
is a safe, quick, and effective treatment with a promising short-term outcome.
This method should be provided as a salvage procedure for patients with a
nonreconstructable ulnar bone defect.
PMID- 27503016
TI - Cognitive Function of Children and Adolescents with Attention Deficit
Hyperactivity Disorder and Learning Difficulties: A Developmental Perspective.
AB - BACKGROUND: The cognitive function of children with either attention deficit
hyperactivity disorder (ADHD) or learning disabilities (LDs) is known to be
impaired. However, little is known about the cognitive function of children with
comorbid ADHD and LD. The present study aimed to explore the cognitive function
of children and adolescents with ADHD and learning difficulties in comparison
with children with ADHD and healthy controls in different age groups in a large
Chinese sample. METHODS: Totally, 1043 participants with ADHD and learning
difficulties (the ADHD + learning difficulties group), 870 with pure ADHD (the
pure ADHD group), and 496 healthy controls were recruited. To investigate the
difference in cognitive impairment using a developmental approach, all
participants were divided into three age groups (6-8, 9-11, and 12-14 years old).
Measurements were the Chinese-Wechsler Intelligence Scale for Children, the
Stroop Color-Word Test, the Trail-Making Test, and the Behavior Rating Inventory
of Executive Function-Parents (BRIEF). Multivariate analysis of variance was
used. RESULTS: The results showed that after controlling for the effect of ADHD
symptoms, the ADHD + learning difficulties group was still significantly worse
than the pure ADHD group, which was, in turn, worse than the control group on
full intelligence quotient (98.66 +/- 13.87 vs. 105.17 +/- 14.36 vs. 112.93 +/-
13.87, P < 0.001). The same relationship was also evident for shift function
(shifting time of the Trail-Making Test, 122.50 [62.00, 194.25] s vs. 122.00
[73.00, 201.50] s vs. 66.00 [45.00, 108.00] s, P< 0.001) and everyday life
executive function (BRIEF total score, 145.71 +/- 19.35 vs. 138.96 +/- 18.00 vs.
122.71 +/- 20.45, P < 0.001) after controlling for the effect of the severity of
ADHD symptoms, intelligence quotient, age, and gender. As for the age groups, the
differences among groups became nonsignificant in the 12-14 years old group for
inhibition (meaning interference of the Stroop Color-Word Test, 18.00 [13.00,
25.00] s vs. 17.00 [15.00, 26.00] s vs. 17.00 [10.50, 20.00] s , P = 0.704) and
shift function (shifting time of the Trail-Making Test, 62.00 [43.00, 97.00] s
vs. 53.00 [38.00, 81.00] s vs. 101.00 [88.00, 114.00] s, P = 0.778). CONCLUSIONS:
Children and adolescents with ADHD and learning difficulties have more severe
cognitive impairment than pure ADHD patients even after controlling for the
effect of ADHD symptoms. However, the differences in impairment in inhibition and
shift function are no longer significant when these individuals were 12-14 years
old.
PMID- 27503017
TI - Self-controlled Study of Onychomycosis Treated with Long-pulsed Nd:YAG 1064-nm
Laser Combined with Itraconazole.
AB - BACKGROUND: Onychomycosis is a fungal infection of the nail plate and subungual
area. In this study, we examined the efficacy of laser treatment using self
controlled study programs involving a long-pulsed Nd:YAG 1064-nm laser combined
with oral medication. METHODS: Self-controlled strategies were followed in this
study. The patients received treatment with oral itraconazole in conjunction with
long-pulsed Nd:YAG 1064-nm laser treatment at the nails of the unilateral limb
once a week for a total of four times. A total of 84 affected nails were divided
into Group A (mild to moderate) and Group B (severe) according to disease
severity. Affected nails with the same Scoring Clinical Index for Onychomycosis
scores were selected to compare the therapeutic effects of the pure medication
treatment group and the combination treatment group with a 24-week follow-up
period. RESULTS: In Group A, at the 8th, 16th, and 24th weeks of follow-up, the
efficacies in the pure medication treatment group were 81.0%, 81.0%, and 90.5%,
respectively, while those in the combination treatment group were 100%, 95.2%,
and 90.5%, respectively. The differences between groups were not significant (8th
week: chi2 = 4.421, P> 0.05; 16th week: chi2 = 2.043, P> 0.05; 24th week: chi2 =
0.00, P > 0.05). In Group B, at the 8th, 16th, and 24th weeks of follow-up, the
efficacies in the pure medication treatment group were 61.9%, 66.7%, and 52.4%,
respectively, while those in the combination treatment group were 95.2%, 90.5%,
and 100%, respectively. The differences between groups at the 8th and 24th weeks
of follow-up were statistically significant (8th week: chi2 = 6.929, P< 0.05;
24th week: chi2 = 13.125, P < 0.05). CONCLUSIONS: For patients with mild or
moderate onychomycosis, we recommended a pure medication treatment or combination
treatment with medication and laser. For those patients with severe
onychomycosis, we recommended a combination of medication and laser therapy.
PMID- 27503018
TI - Usage of a Reward System for Dealing with Pediatric Dental Fear.
AB - BACKGROUND: Pediatric dental fear, if left unchecked, can persist for a lifetime
and adversely impact the physical and psychological health of a patient. In this
study, a feasible nonmedical method for relieving pediatric dental fear was
investigated. METHODS: A randomized, single-blind, controlled trial model was
applied. The juvenile patients experiencing dental fear, whose parents or
guardian had signed an informed consent form, were randomly divided into two
groups. Group A (n = 50) was the control group, while Group B (n = 50) was the
reward group. Participants in Group A accepted routine treatment. Participants in
Group B were told that they would obtain a gift as a rewarda for their good
behavior if they were compliant during their dental treatments. The Chinese
version of the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) was used
to evaluate the level of dental fear of each patient both before and after each
treatment. A contrast analysis and a correlation analysis of the results were
used to assess the efficacy of the reward mechanism. RESULTS: All participants in
Group B, were obedient during the dental treatment, and they also successfully
chose the present they wanted at the end of their dental treatment. Children at
different ages showed different reward preferences. Significant difference in the
fear scores of the participants in Group B before the treatment and after
receiving the reward was found (independent samples t-test, t = 14.72, P <
0.001). In Group A, 86% children's fear score did not undergo a noticeable
change. CONCLUSIONS: A reward system is proved feasible to relieve pediatric
dental fear, and the form of reward should meet the demand of patients.
PMID- 27503019
TI - Viral and Bacterial Etiology of Acute Diarrhea among Children under 5 Years of
Age in Wuhan, China.
AB - BACKGROUND: Acute diarrhea remains the serious problem in developing countries,
especially among children under 5 years of age. Currently, only two or three
common diarrhea pathogens were screened at most hospitals in China. The aim of
this study was to provide a wide variety of diarrhea pathogens and their
antimicrobial resistance patterns in children under 5 years of age. METHODS:
Totally 381 stool samples collected from Tongji Hospital between July 1, 2014 and
June 30, 2015 were tested by culture and/or polymerase chain reaction for eight
kinds of bacteria and five kinds of viruses. An antimicrobial sensitivity test
was performed using dilution method recommended by the Clinical and Laboratory
Standards Institute. RESULTS: Viral infections were mainly identified in infants
(0-11 months), whereas bacterial infections were more prevalent in the age of 24
59 months. About 69.8% of samples were positive for at least one pathogen, 51.7%
of samples were virus positive, followed by bacteria positive cases (19.4%), and
12.6% of cases displayed co-infections with two viruses or a virus and a
bacterium. Rotavirus was the most prevalent pathogen, followed closely by
norovirus, while Salmonella was the most commonly isolated bacteria, followed by
diarrheagenic Escherichia coli (DEC) and Campylobacter. More than 40% of
Salmonella spp. and DEC isolates were resistant to first-line antibiotics
(ampicillin, trimethoprim-sulfamethoxazole, and tetracycline). Around 10% of
Salmonella spp. isolates were resistant to ceftriaxone and ciprofloxacin
simultaneously. Campylobacter spp. displayed high resistance to ciprofloxacin but
kept low resistance to azithromycin and doxycycline. CONCLUSIONS: The etiology of
acute diarrhea varies in children of different age groups. The high frequency of
infection with viruses suggests the urgent demand for new viral vaccine
development. Proper use of antibiotics in the treatment of acute diarrhea is
crucial due to the high level of antibiotic resistance.
PMID- 27503020
TI - Clinical and Molecular Characteristics in 100 Chinese Pediatric Patients with
m.3243A>G Mutation in Mitochondrial DNA.
AB - BACKGROUND: Mitochondrial diseases are a group of energy metabolic disorders with
multisystem involvements. Variable clinical features present a major challenge in
pediatric diagnoses. We summarized the clinical spectrum of m.3243A>G mutation in
Chinese pediatric patients, to define the common clinical manifestations and
study the correlation between heteroplasmic degree of the mutation and clinical
severity of the disease. METHODS: Clinical data of one-hundred pediatric patients
with symptomatic mitochondrial disease harboring m.3243A>G mutation from 2007 to
2013 were retrospectively reviewed. Detection of m.3243A>G mutation ratio was
performed by polymerase chain reaction (PCR)-restriction fragment length
polymorphism. Correlation between m.3243A>G mutation ratio and age was evaluated.
The differences in clinical symptom frequency of patients with low, middle, and
high levels of mutation ratio were analyzed by Chi-square test. RESULTS: Sixty
six patients (66%) had suffered a delayed diagnosis for an average of 2 years.
The most frequent symptoms were seizures (76%), short stature (73%), elevated
plasma lactate (70%), abnormal magnetic resonance imaging/computed tomography
(MRI/CT) changes (68%), vomiting (55%), decreased vision (52%), headache (50%),
and muscle weakness (48%). The mutation ratio was correlated negatively with
onset age (r = -0.470, P < 0.001). Myopathy was more frequent in patients with a
high level of mutation ratio. However, patients with a low or middle level of
m.3243A>G mutation ratio were more likely to suffer hearing loss, decreased
vision, and gastrointestinal disturbance than patients with a high level of
mutation ratio. CONCLUSIONS: Our study showed that half of Chinese pediatric
patients with m.3243A>G mutation presented seizures, short stature, abnormal
MRI/CT changes, elevated plasma lactate, vomiting, and headache. Pediatric
patients with these recurrent symptoms should be considered for screening
m.3243A>G mutation. Clinical manifestations and laboratory abnormalities should
be carefully monitored in patients with this point mutation.
PMID- 27503021
TI - Vascular Endothelial Growth Factor and Cluster of Differentiation 34 for
Assessment of Perioperative Bleeding Risk in Gastric Cancer Patients.
AB - BACKGROUND: Angiogenesis is the formation of new blood vessels to supply
nutrients to tumors. Vascular endothelial growth factor (VEGF) and cluster of
differentiation 34 (CD34) are important signaling proteins involved in
angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to
tumor progression. This study focused on the relationship between VEGF, CD34, and
perioperative hemorrhage in patients with gastric cancer. METHODS: To observe the
relationship between VEGF and CD34, we tracked 112 patients with advanced gastric
cancer for 5 years to assess factors related to hemorrhage, using
immunohistochemistry. The results were subjected to statistical analysis using a
2 * 2 contingency table, logistic regression, and receiver operating
characteristic (ROC) test. RESULTS: The concentrations of VEGF and CD34 were
critically correlated with perioperative hemorrhage and neural invasion in
patients with gastric cancer (P < 0.05). Expression of VEGF and CD34 was related
(P < 0.05, chi2 = 6.834). VEGF and CD34 co-expression strongly increased the risk
of preoperative bleeding (area under the ROC curve >0.7, P < 0.05). CONCLUSIONS:
Expression of VEGF and CD34 was critically correlated with perioperative
hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an
effective indicator for evaluating the risk of perioperative bleeding in gastric
cancer patients.
PMID- 27503022
TI - Ginsenoside Rd Attenuates DNA Damage by Increasing Expression of DNA Glycosylase
Endonuclease VIII-like Proteins after Focal Cerebral Ischemia.
AB - BACKGROUND: Ginsenoside Rd (GSRd), one of the main active ingredients in
traditional Chinese herbal Panax ginseng, has been found to have therapeutic
effects on ischemic stroke. However, the molecular mechanisms of GSRd's
neuroprotective function remain unclear. Ischemic stroke-induced oxidative stress
results in DNA damage, which triggers cell death and contributes to poor
prognosis. Oxidative DNA damage is primarily processed by the base excision
repair (BER) pathway. Three of the five major DNA glycosylases that initiate the
BER pathway in the event of DNA damage from oxidation are the endonuclease VIII
like (NEIL) proteins. This study aimed to investigate the effect of GSRd on the
expression of DNA glycosylases NEILs in a rat model of focal cerebral ischemia.
METHODS: NEIL expression patterns were evaluated by quantitative real-time
polymerase chain reaction in both normal and middle cerebral artery occlusion
(MCAO) rat models. Survival rate and Zea-Longa neurological scores were used to
assess the effect of GSRd administration on MCAO rats. Mitochondrial DNA (mtDNA)
and nuclear DNA (nDNA) damages were evaluated by the way of real-time analysis of
mutation frequency. NEIL expressions were measured in both messenger RNA (mRNA)
and protein levels by quantitative polymerase chain reaction and Western blotting
analysis. Apoptosis level was quantitated by the expression of cleaved caspase-3
and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling
assay. RESULTS: We found that GSRd administration reduced mtDNA and nDNA damages,
which contributed to an improvement in survival rate and neurological function;
significantly up-regulated NEIL1 and NEIL3 expressions in both mRNA and protein
levels of MCAO rats; and reduced cell apoptosis and the expression of cleaved
caspase-3 in rats at 7 days after MCAO. CONCLUSIONS: Our results indicated that
the neuroprotective function of GSRd for acute ischemic stroke might be partially
explained by the up-regulation of NEIL1 and NEIL3 expressions.
PMID- 27503023
TI - Cryobiological Characteristics of L-proline in Mammalian Oocyte Cryopreservation.
AB - BACKGROUND: L-proline is a natural, nontoxic cryoprotectant that helps cells and
tissues to tolerate freezing in a variety of plants and animals. The use of L
proline in mammalian oocyte cryopreservation is rare. In this study, we explored
the cryobiological characteristics of L-proline and evaluated its protective
effect in mouse oocyte cryopreservation. METHODS: The freezing property of L
proline was detected by Raman spectroscopy and osmometer. Mature oocytes obtained
from 8-week-old B6D2F1 mice were vitrified in a solution consisting various
concentration of L-proline with a reduced proportion of dimethyl sulfoxide (DMSO)
and ethylene glycol (EG), comparing with the control group (15% DMSO and 15% EG
without L-proline). The survival rate, 5-methylcytosine (5-mC) expression,
fertilization rate, two-cell rate, and blastocyst rate in vitro were assessed by
immunofluorescence and in vitro fertilization. Data were analyzed by Chi-square
test. RESULTS: L-proline can penetrate the oocyte membrane within 1 min. The
osmotic pressure of 2.00 mol/L L-proline mixture is similar to that of the
control group. The survival rate of the postthawed oocyte in 2.00 mol/L L-proline
combining 7.5% DMSO and 10% EG is significantly higher than that of the control
group. There is no difference of 5-mC expression between the L-proline
combination groups and control. The fertilization rate, two-cell rate, and
blastocyst rate in vitro from oocyte vitrified in 2.00 mol/L L-proline combining
7.5% DMSO and 10% EG solution are similar to that of control. CONCLUSIONS: It
indicated that an appropriate concentration of L-proline can improve the
cryopreservation efficiency of mouse oocytes with low concentrations of DMSO and
EG, which may be applicable to human oocyte vitrification.
PMID- 27503024
TI - Comparison between Minimally Invasive Transforaminal Lumbar Interbody Fusion and
Conventional Open Transforaminal Lumbar Interbody Fusion: An Updated Meta
analysis.
AB - BACKGROUND: The previous studies agree that minimally invasive transforaminal
lumbar interbody fusion (MIS-TLIF) has better function outcomes, less blood loss,
and shorter hospital stay, when compared to open-TLIF. However, there are no
significance differences on operative time, complication, and reoperation rate
between the two procedures. This could be from less relative literatures and
lower grade evidence. The further meta-analysis is needed with more and higher
grade evidences to compare the above two TLIF procedures. METHODS: Prospective
and retrospective studies that compared open-TLIF and MIS-TLIF were identified by
searching the Medline, Embase, Web of Science, China National Knowledge
Infrastructure, Wanfang, and VIP database (the literature search comprised
Medical Subject Heading terms and key words or Emtree term). The retrieval time
ranged from the date when the database was founded to January 2015. Pooled risk
ratios (RR s) and weighted mean differences (WMDs) with 95% confidence intervals
were calculated for the clinical outcomes and perioperative data. RESULTS: Twenty
four studies (n = 1967 patients) were included in this review (n = 951, open
TLIF, n = 1016, MIS-TLIF). MIS-TLIF was associated with a significant decrease in
the visual analog score (VAS)-back pain score (WMD = -0.44; P = 0.001), Oswestry
Disabilities Index (WMD = -1.57; P = 0.005), early ambulation (WMD = -1.77; P =
0.0001), less blood loss (WMD = -265.59; P < 0.00001), and a shorter hospital
stay (WMD = -1.89; P < 0.0001). However, there were no significant differences in
the fusion rate (RR = 0.99; P = 0.34), VAS-leg pain (WMD = -0.10; P = 0.26),
complication rate (RR = 0.84; P = 0.35), operation time (WMD = -5.23; P = 0.82),
or reoperation rate (RR = 0.73; P = 0.32). CONCLUSIONS: MIS-TLIF resulted in a
similar fusion rate with better functional outcome, less blood loss, shorter
ambulation, and hospital stay; furthermore, it did not increase the complication
or reoperation rate based on the existing evidence.
PMID- 27503025
TI - Synovial Fluid C-reactive Protein as a Diagnostic Marker for Periprosthetic Joint
Infection: A Systematic Review and Meta-analysis.
AB - BACKGROUND: Periprosthetic joint infection (PJI) is the main cause of failure
following total joint arthroplasty. Until now, the diagnosis of PJI is still
confronted with technical limitations, and the question of whether synovial fluid
biomarker, C-reactive protein (CRP), can provide high value in the diagnosis of
PJI remains unanswered and, therefore, was the aim of the study. METHODS: First,
we conducted a systematic review on CRP in the diagnosis of PJI by searching
online databases using keywords such as "periprosthetic joint infection",
"synovial fluid", and "C-reactive protein". Eligible studies providing sufficient
data to construct 2 * 2 contingency tables were then selected based on the list
of criteria and the quality of included studies was assessed subsequently.
Finally, the reported sensitivity, specificity, diagnostic odds ratio (DOR),
summary receiver operating characteristic (SROC) curve, and the area under the
SROC (AUSROC) were pooled together and used to evaluate overall diagnostic
performance. RESULTS: Seven studies were included in our review, six of which
comprising a total of 456 participants were further investigated in our meta
analysis. The pooled sensitivity, specificity, and DOR were 0.92 (95% confidence
interval [CI]: 0.86-0.96), 0.90 (95% CI: 0.87-0.93), and 101.40 (95% CI: 48.07
213.93), respectively. The AUSROC was 0.9663 (standard error, 0.0113).
CONCLUSIONS: Synovial fluid CRP is a good biomarker for the diagnosis of PJI with
high sensitivity and specificity.
PMID- 27503027
TI - Corrigendum: Preparation and Characterization of Paclitaxel-loaded Poly Lactic
Acid-co-glycolic Acid Coating Tracheal Stent.
PMID- 27503026
TI - Cerebrospinal Fluid Leakage after Thoracic Decompression.
AB - OBJECTIVE: The objective of this study is to review cerebrospinal fluid leakage
(CSFL) after thoracic decompression and describe its regular and special
features. DATA SOURCES: Literature cited in this review was retrieved from PubMed
and Medline and was primarily published during the last 10 years. "Cerebrospinal
fluid", "leakage", "dural tears", and "thoracic decompression" were the indexed
terms. Relevant citations in the retrieved articles were also screened to include
more data. STUDY SELECTION: All retrieved literature was scrutinized, and four
categories were recorded: incidence and risk factors, complications, treatment
modalities, and prognosis. RESULTS: CSFL is much more frequent after thoracic
decompression than after cervical and lumbar spinal surgeries. Its occurrence is
related to many clinical factors, especially the presence of ossified ligaments
and the adhesion of the dural sac. While its impact on the late neurological
recovery is currently controversial, CSFL increases the risk of other
perioperative complications, such as low intracranial pressure symptoms,
infection, and vascular events. The combined use of primary repairs during the
operation and conservative treatment postoperatively is generally effective for
most CSFL cases, whereas lumbar drains and reoperations should be implemented as
rescue options for refractory cases only. CONCLUSIONS: CSFL after thoracic
decompression has not been specifically investigated, so the present study
provides a systematic and comprehensive review of the issue. CSFL is a multi
factor-related complication, and pathological factors play a decisive role. The
importance of CSFL is in its impact on the increased risk of other complications
during the postoperative period. Methods to prevent these complications are in
need. In addition, though the required treatment resources are not special for
CSFL after thoracic decompression, most CSFL cases are conservatively curable,
and surgeons should be aware of it.
PMID- 27503028
TI - Idebenone Maintains Survival of Mutant Myocilin Cells by Inhibiting Apoptosis.
PMID- 27503029
TI - Surgical Repair and Detection of Cerebrospinal Fluid Rhinorrhea using Magnetic
Resonance Cisternography and Skull Base Coronal Thin-section Computed Tomography
Scan.
PMID- 27503030
TI - Three Cases of Idiopathic Superior Laryngeal Neuralgia Treated by Superior
Laryngeal Nerve Block under Ultrasound Guidance.
PMID- 27503031
TI - Symptomatic Rathke's Cleft Cyst with Rapid Enlargement Masquerading as Rathke's
Cleft Cyst Apoplexy.
PMID- 27503032
TI - Adult Monosymptomatic Nocturnal Enuresis with Obstructive Sleep Apnea Syndrome.
PMID- 27503033
TI - First Case of Laboratory-confirmed Zika Virus Infection Imported into China.
PMID- 27503034
TI - Single-puncture Method of Laparoscopic Herniorrhaphy in Children.
PMID- 27503035
TI - Treatment of In-Stent Restenosis in Patients with Renal Artery Stenosis.
AB - PURPOSE: To determine clinical outcomes of patients treated for renal artery in
stent restenosis (ISR) with atherosclerotic renal artery stenosis. MATERIALS AND
METHODS: A retrospective review was performed of the clinical data of all
patients who underwent renal artery stent placement for atherosclerotic renal
artery stenosis from 1996 to 2009. Medical records of patients were reviewed for
relevant clinical history, including blood pressure, antihypertensive
medications, and renal function data before and after an intervention. In 1,052
patients, 1,090 renal artery stent placements were performed. Of these, 101
stents in 79 patients developed ISR, which was treated with either percutaneous
transluminal angioplasty (PTA) or repeat stent placement. Procedural details,
including modality of intervention, stent diameter, and time to restenosis, were
recorded. Hypertensive agent and use of statins were recorded. Univariate
analysis was performed to identify risk factors associated with restenosis after
treatment of ISR. RESULTS: Patients treated with repeat stent placement were 6.89
times more likely to lose patency after treatment than patients treated with PTA
(P < .01). No additional clinical or procedural factor, including smoking
history; presence of cardiac, renal, or metabolic disease; use of statin at time
of ISR treatment; or diameter of treatment (stent or PTA), had a significant
association with duration of stent or angioplasty patency. CONCLUSIONS: Treatment
of renal artery ISR with PTA among patients with atherosclerotic renal artery
stenosis has a lower rate of subsequent ISR compared with repeat stent placement.
PMID- 27503036
TI - An online psychological intervention can improve the sexual satisfaction of men
following treatment for localized prostate cancer: outcomes of a Randomised
Controlled Trial evaluating My Road Ahead.
AB - BACKGROUND: Prostate cancer treatment often results in significant psycho-sexual
challenges for men following treatment; however, many men report difficulty in
accessing appropriate care. METHODS: A randomized controlled trial was undertaken
to assess the efficacy of a 10-week self-guided online psychological intervention
called My Road Ahead (MRA) for men with localized prostate cancer in improving
sexual satisfaction. Participants were randomized to 1 of 3 conditions MRA alone
or MRA plus online forum, or forum access alone. Pre, post, and follow-up
assessments of overall sexual satisfaction were conducted. Mixed models and
structural equation modeling were used to analyze the data. RESULTS: One hundred
forty-two men (mean age 61 y; SD = 7) participated. The majority of participants
had undergone radical prostatectomy (88%) and all men had received treatment for
localized prostate cancer. Significant differences were obtained for the 3 groups
(P = .026) and a significant improvement in total sexual satisfaction was
observed only for participants who were allocated to MRA + forum with a large
effect size (P = .004, partial eta2 = 0.256). Structural equation modeling
indicated that increases in sexual function, masculine self-esteem, and sexual
confidence contributed significantly to overall sexual satisfaction for the MRA +
forum plus forum condition. CONCLUSIONS: This study is the first, to our
knowledge, that has evaluated a self-guided online psychological intervention
tailored to the specific needs of men with prostate cancer. The findings indicate
the potential for MRA to deliver support that men may not otherwise receive and
also highlight the importance of psychological intervention to facilitate
improved sexual outcomes.
PMID- 27503038
TI - Cognition Effects of Low-Grade Hypoxia.
AB - INTRODUCTION: The effects of low-grade hypoxia on cognitive function are reported
in this paper. The study compared cognitive function during short exposures at
four different altitudes. METHODS: Ninety-one subjects were exposed to simulated
altitudes of ground level, 1524, 2438, and 3658 m (5000, 8000, and 12,000 ft) in
the Brooks City-Base altitude pressure chamber in a balanced design. Oxygen
saturation, heart rate, and cognitive performance on seven different cognitive
tasks were measured. In addition, subjects indicated their symptoms from a 33
item subjective symptom survey. RESULTS: As designed, oxygen saturation decreased
and heart rate increased with higher altitudes. Very small degradations in
performance were found at the two highest altitudes for only two of the cognitive
tasks (continuous performance and grammatical reasoning). In the subjective
symptom survey, 18 of the 33 possible symptoms were more common at 3658 m (12,000
ft) than at ground level. CONCLUSIONS: The findings indicated a minimal influence
of low-grade hypoxia on cognitive performance in contrast to some existing
classic symptoms of hypoxia. Pilmanis AA, Balldin UI, Fischer JR. Cognition
effects of low-grade hypoxia. Aerosp Med Hum Perform. 2016; 87(7):596-603.
PMID- 27503039
TI - Frequency, Not Amplitude, of Latency Affects Subjective Sickness in a Head
Mounted Display.
AB - BACKGROUND: Interactions between frequency and amplitude of latency in head
mounted displays (HMDs) are thought to affect simulator sickness. Many studies
have linked system latency to subjective sickness, but recent research has found
that at least with the case of inertia-based head tracking technology, latency is
not a constant; rather it varies systematically over time due to sensor errors
and clock asynchronization. The purpose of this experiment was to further explore
the relationship between frequency and amplitude of latency as they relate to
subjective sickness experienced in an HMD. METHODS: In a 2 (frequency) * 2
(amplitude) design, 120 subjects were randomly assigned to 4 latency conditions.
Frequency of latency was either 0.2 Hz or 1.0 Hz. Amplitude of latency was either
100 ms fixed or 20-100 ms varying. RESULTS: A main effect of frequency of latency
was found. Subjects reported greater sickness in the 0.2-Hz frequency conditions
(39.0 +/- 27.8) compared to the 1-Hz conditions (30.3 +/- 17.0). Additionally, 18
subjects withdrew their participation early in the 0.2-Hz conditions compared to
7 in the 1.0-Hz conditions. DISCUSSION: In conclusion, frequency of latency
appears to play a role in the experience of sickness in HMDs in both subjective
reporting of symptoms and subject performance. The current study confirms results
of earlier studies, finding that real motion around a frequency of 0.2 Hz is more
sickening than other frequencies. Future work should continue to parse the
effects of frequency and amplitude of latency in head-tracked HMDs. Kinsella A,
Mattfeld R, Muth E, Hoover A. Frequency, not amplitude, of latency affects
subjective sickness in a head-mounted display. Aerosp Med Hum Perform. 2016;
87(7):604-609.
PMID- 27503040
TI - Neuromuscular Adaptations Following 90 Days Bed Rest With or Without Resistance
Exercise.
AB - INTRODUCTION: This study examined the effects of long-term bed rest with or
without a concurrent resistance exercise protocol on different muscle function
indices of the knee extensors and their influence on previously shown atrophy,
neural impairment, and slow-to-fast phenotype shift. METHODS: Nine men underwent
90 d of bed rest only (BR), while eight men in addition performed maximal supine
squats every third day (BRE). Before and at day 1 and 5 following bed rest,
surface quadriceps electromyographic (EMG) activity was measured during a
sustained (60-s) submaximal isometric action and rate of force development (RFD)
was assessed during a maximal isometric action, both in the supine squat
position. Maximal torque was measured during isokinetic knee extensions at
different angular velocities before and after (day 2 and 11) bed rest. RESULTS:
EMG amplitude at a fixed submaximal load increased in BR, but not in BRE. The
increase in amplitude during the sustained action was elevated in BR but not in
BRE. RFD decreased in BR; this effect was attenuated day 1 and normalized day 5
in BRE. RFD expressed relative to maximal force was maintained in both groups.
Angle-specific torque decreased equally for all velocities in BR. The decrease in
isokinetic strength was attenuated day 2 in BRE. DISCUSSION: Phenotype changes
were not reflected in muscle function measurements, probably because they were
overridden by the effects of atrophy and neural adaptation. The protective effect
of resistance exercise was more pronounced in tasks similar to the training
action, inferring great impact of neural mechanisms. Alkner BA, Norrbrand L,
Tesch PA. Neuromuscular adaptations following 90 days bed rest with or without
resistance exercise. Aerosp Med Hum Perform. 2016; 87(7):610-617.
PMID- 27503041
TI - Aeromedical Hazard Comparison of FAA Medically Certified Third-Class and
Medically Uncertified Pilots.
AB - BACKGROUND: Since 2004, in the United States, light sport aircraft (LSA) and some
aircraft with standard airworthiness certificates can be operated for
recreational purposes with a valid state driver's license rather than a Federal
Aviation Administration (FAA)-issued aeromedical certificate. There have been
recent efforts to allow operation of much larger, heavier, faster, and more
complex aircraft without requiring a medical certificate. The primary objective
of this research was to compare hazards to flight safety identified in fatally
injured pilots required to possess a valid FAA third-class medical certificate to
hazards in fatally injured pilots who were not required to possess a valid
medical certificate. METHODS: A search of all fatal U.S. aircraft accidents in
the FAA Medical ANalysis and TRAcking (MANTRA) registry between January 1, 2011,
and April 30, 2014, identified 1084 individuals. A review of accident pilots'
medical, autopsy, and toxicological data was conducted. After applying exclusion
criteria, 467 pilots remained, including 403 medically certified and 64 medically
uncertified pilots. RESULTS: A significant difference was found in a surrogate
measure for risk between medically certified and uncertified pilots (25% vs.
59%). This difference remained significant after adjustment for age. No
significant difference was found in the proportions of hazards identified on
toxicological review. CONCLUSION: The results of this study suggest that the risk
of an adverse medical event is reduced in pilots required to possess a valid
medical certificate. Ricaurte EM, Mills WD, DeJohn CA, Laverde-Lopez MC, Porras
Sanchez DF. Aeromedical hazard comparison of FAA medically certified third-class
and medically uncertified pilots. Aerosp Med Hum Perform. 2016; 87(7):618-621.
PMID- 27503042
TI - Cognitive Performance Effects of Bilastine 20 mg During 6 Hours at 8000 ft Cabin
Altitude.
AB - INTRODUCTION: Bilastine is a new oral, second generation antihistamine used in
the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. It is
considered a nonsedating antihistamine and might be recommended for use in
pilots, pending research on the effects on flying-related performance under
hypobaric conditions that prevail in an airliner. We assessed the effects of a
single dose of bilastine 20 mg on alertness and complex task performance of
healthy volunteers in a hypobaric chamber at 75.2 kPa (8000 ft/2438 m cabin
altitude). METHODS: In a randomized, double-blind, crossover study, 24 volunteers
received a single dose of bilastine 20 mg, hydroxyzine 50 mg (active control),
and placebo. Using the Vigilance and Tracking Task, Multi-Attribute Task Battery,
and Stanford Sleepiness Scale, assessments were made before and up to 6 h after
intake of the study medication. RESULTS: Bilastine 20 mg had no impairing effects
on sleepiness levels, vigilance, or complex task performance for up to 6 h post
dose. Hydroxyzine 50 mg (active control) was associated with significant
sleepiness and impaired performance across this time period, confirming the
sensitivity of the tests. CONCLUSION: Bilastine 20 mg did not cause sleepiness or
impaired performance on tasks related to flying. It is anticipated that a single
dose of bilastine 20 mg will not affect flying performance. Bilastine may provide
a safe therapeutic alternative for pilots suffering from allergic rhinitis or
urticaria. Our findings might also have implications for the treatment of
allergic disorders of personnel involved in other safety-sensitive jobs. Valk
PJL, Simons R, Jetten AM, Valiente R, Labeaga L. Cognitive performance effects of
bilastine 20 mg during 6 hours at 8000 ft cabin altitude. Aerosp Med Hum Perform.
2016; 87(7):622-627.
PMID- 27503043
TI - Demographic, Lifestyle Factors, and Reasons for Use of Dietary Supplements by Air
Force Personnel.
AB - BACKGROUND: Dietary supplement (DS) use is common among U.S. Army personnel to
purportedly improve health, provide energy, and increase strength. However, a
comprehensive analysis of DS use among U.S. Air Force (USAF) personnel has not
been conducted using the same survey instrument, which would permit direct
comparisons to DS use by Army personnel. METHODS: A standardized questionnaire
was used to assess DS use, demographic factors, and reasons for use of DS by USAF
personnel (N = 1750). Logistic regression models adjusted for age, sex, and rank
were used to determine relationships among categories of DS (multivitamin and
multimineral, individual vitamins and minerals, protein/amino acid supplements,
combination products, herbal supplements, purported steroid analogs, and other)
and demographic factors. Findings were compared to reports from other military
services and civilian populations. RESULTS: DS were used by 68% of USAF
personnel: 35% used 1-2 DS >= 1 time/wk, 13% 3-4 DS >= 1 time/wk, and 20% >= 5 DS
>= 1 time/wk. There were 45% of personnel who used a multivitamin and mineral,
33% protein supplements, 22% individual vitamins/minerals, 22% combination
products, and 7% herbals. Logistic regression demonstrated aerobic exercise
duration and strength training were associated with increased DS use. Individuals
who previously deployed were more likely to use DS. CONCLUSIONS: Like Army
personnel, college students and athletes, USAF personnel use more DS than the
general population and are more likely to use purported performance enhancing DS,
such as protein supplements, and concurrently consume multiple DS. Austin KG,
Price LL, McGraw SM, Leahy G, Lieberman HR. Demographic, lifestyle factors, and
reasons for use of dietary supplements by Air Force personnel. Aerosp Med Hum
Perform. 2016; 87(7):628-637.
PMID- 27503044
TI - Sleep Disturbance in Female Flight Attendants and Teachers.
AB - BACKGROUND: Flight attendants (FAs) may experience circadian disruption due to
travel during normal sleep hours and through multiple time zones. This study
investigated whether FAs are at higher risk for sleep disturbance compared to
teachers, as assessed by questionnaire, diary, and activity monitors. METHODS:
Sleep/wake cycles of 45 FAs and 25 teachers were studied. For one menstrual
cycle, participants wore an activity monitor and kept a daily diary. Sleep
metrics included total sleep in the main sleep period (MSP), sleep efficiency
(proportion of MSP spent sleeping), and nocturnal sleep fraction (proportion of
sleep between 10 p.m. to 8 a.m. home time). Relationships between sleep metrics
and occupation were analyzed with mixed and generalized linear models. RESULTS:
Both actigraph and diary data suggest that FAs sleep longer than teachers.
However, several actigraph indices of sleep disturbance indicated that FAs
incurred significant impairment of sleep compared to teachers. FAs were more
likely than teachers to have poor sleep efficiency [adjusted odds ratio (OR) for
lowest quartile of sleep efficiency = 1.9, 95% Confidence Interval (CI) 1.2 -
3.0] and to have a smaller proportion of their sleep between 10 p.m. and 8 a.m.
home time (adjusted OR for lowest quartile of nocturnal sleep fraction = 3.1, CI
1.1 -9.0). DISCUSSION: Study FAs experienced increased sleep disturbance compared
to teachers, which may indicate circadian disruption. Grajewski B, Whelan EA,
Nguyen MM, Kwan L, Cole RJ. Sleep disturbance in female flight attendants and
teachers. Aerosp Med Hum Perform. 2016; 87(7)638-645.
PMID- 27503045
TI - Gaze Behavior While Operating a Complex Instrument Control Task.
AB - INTRODUCTION: The recent developments of technology in almost all areas of
industrial processing, workplace, smart homes, mobility, media, and communication
change humans' everyday life environment and behavioral responses in numerous
ways. Our main objective in this study was to determine whether subjects'
operator performance in a complex sensorimotor task is associated with their gaze
behavior. METHODS: In two experiments subjects operated a complex control task.
To this end they watched multiple displays, made strategic decisions, and used
multiple actuators to maximize their virtual earnings from operating a virtual
power plant. In Experiment 1 we compared gaze behavior during the tasks with
respect to operator performance in two different age groups (young vs. old), and
in Experiment 2 in two different gravity conditions (normal vs. microgravity).
RESULTS: We found gaze pattern changed in older subjects as well as in
microgravity. Older adults and subjects in microgravity looked longer at areas
that are less relevant for task success. Most importantly, these changes in gaze
pattern accounted for the effects of age and microgravity and on total earnings
in the instrument-control task. DISCUSSION: In conclusion, age- and gravity
related changes of gaze behavior show a similar pattern. Gaze behavior seems to
play an important role in complex control tasks and might predict alterations of
operational performance. Kalicinski M, Steinberg F, Dalecki M, Bock O. Gaze
behavior while operating a complex instrument control task. Aerosp Med Hum
Perform. 2016; 87(7):646-651.
PMID- 27503046
TI - Personal Flying Accident Rates of Selected Light Sport Aircraft Compared with
General Aviation Aircraft.
AB - BACKGROUND: The issue of expanding flight privileges that do not require medical
oversight is currently an important topic, especially in the United States. We
compared personal flying accident rates in aircraft with special light sport
aircraft (SLSA) and experimental light sport aircraft (ELSA) airworthiness
certificates to accident rates for personal flying in other general aviation (GA)
aircraft. METHODS: To calculate accident rates, personal flying hours were
obtained from the annual FAA General Aviation and Part 135 Activity Surveys, and
numbers of personal flying accidents were obtained from the NTSB accident
database. Overall and fatal personal flying accident rates for the SLSA and ELSA
groups and other GA aircraft were calculated and accident rates were compared.
RESULTS: The overall personal flying accident rate for SLSA and ELSA was found to
be 29.8 per 100,000 flight hours and the fatal accident rate was 5.2 per 100,000
flying hours. These are both significantly greater than the overall personal
flying rate of 12.7 per 100,000 h and fatal rate of 2.6 per 100,000 h for other
GA aircraft. DISCUSSION: Although this study has several limitations, the
significantly higher accident rates in the sport pilot aircraft suggests caution
when expanding sport pilot privileges to include larger, more complex aircraft.
Mills WD, DeJohn CA. Personal flying accident rates of selected light sport
aircraft compared with general aviation aircraft. Aerosp Med Hum Perform. 2016;
87(7):652-654.
PMID- 27503047
TI - A Report of Transverse Process Fractures Secondary to the Centrifuge in a Healthy
Aviator.
AB - BACKGROUND: Centrifuge training, while an integral component in pilot training,
is not without risks. To date there has never been a reported case of isolated
transverse process fractures associated with centrifuge training. CASE REPORT: A
32-yr-old Flight Surgeon underwent centrifuge training as part of an educational
course. She had increasing back pain after exposure to the centrifuge. Follow-up
studies showed left L2 and bilateral L3 transverse process fractures. No other
contributory causes could be identified except for mild vitamin D deficiency.
DISCUSSION: The etiology, incidence, and treatment of transverse process
fractures are examined to better prepare the clinician for the management of
these cases. Puderbaugh MA. A report of transverse process fractures secondary to
the centrifuge in a healthy aviator. Aerosp Med Hum Perform. 2016; 87(7):655-658.
PMID- 27503048
TI - Use of Gene Expression Biomarkers to Predict Suicidality.
AB - Since the tragic accident of Germanwings flight 4U9525, there has been discussion
about methods to identify and prevent suicidality in pilots. Neurogenetic
scientists claim that biomarker tests for suicidality as part of healthcare
assessments may lead to early identification of suicidal behavior. In this
commentary the value of these gene expression biomarkers for aeromedical purposes
is evaluated based on relevant literature. It is concluded that the currently
identified biomarkers for suicidality need thorough validation before they can be
used. The aeromedical examiner's most important tool is still an anamnesis, in
which warning signs of suicidal behavior can be picked up. Simons R. Use of gene
expression biomarkers to predict suicidality. Aerosp Med Hum Perform. 2016;
87(7):659-660.
PMID- 27503049
TI - You're the Flight Surgeon.
AB - Rojas J. You're the flight surgeon: F-16 pilot with papular rash. Aerosp Med Hum
Perform. 2016; 87(7):661-663.
PMID- 27503050
TI - This Month in Aerospace Medicine History.
PMID- 27503052
TI - In silico modeling for tumor growth visualization.
AB - BACKGROUND: Cancer is a complex disease. Fundamental cellular based studies as
well as modeling provides insight into cancer biology and strategies to treatment
of the disease. In silico models complement in vivo models. Research on tumor
growth involves a plethora of models each emphasizing isolated aspects of benign
and malignant neoplasms. Biologists and clinical scientists are often overwhelmed
by the mathematical background knowledge necessary to grasp and to apply a model
to their own research. RESULTS: We aim to provide a comprehensive and expandable
simulation tool to visualizing tumor growth. This novel Web-based application
offers the advantage of a user-friendly graphical interface with several
manipulable input variables to correlate different aspects of tumor growth. By
refining model parameters we highlight the significance of heterogeneous
intercellular interactions on tumor progression. Within this paper we present the
implementation of the Cellular Potts Model graphically presented through
Cytoscape.js within a Web application. The tool is available under the MIT
license at https://github.com/davcem/cpm-cytoscape and
http://styx.cgv.tugraz.at:8080/cpm-cytoscape/ . CONCLUSION: In-silico methods
overcome the lack of wet experimental possibilities and as dry method succeed in
terms of reduction, refinement and replacement of animal experimentation, also
known as the 3R principles. Our visualization approach to simulation allows for
more flexible usage and easy extension to facilitate understanding and gain novel
insight. We believe that biomedical research in general and research on tumor
growth in particular will benefit from the systems biology perspective.
PMID- 27503053
TI - AC105 Increases Extracellular Magnesium Delivery and Reduces Excitotoxic
Glutamate Exposure within Injured Spinal Cords in Rats.
AB - Magnesium (Mg2+) homeostasis is impaired following spinal cord injury (SCI) and
the loss of extracellular Mg2+ contributes to secondary injury by various
mechanisms, including glutamate neurotoxicity. The neuroprotective effects of
high dose Mg2+ supplementation have been reported in many animal models. Recent
studies found that lower Mg2+ doses also improved neurologic outcomes when Mg2+
was formulated with polyethylene glycol (PEG), suggesting that a PEG/ Mg2+
formulation might increase Mg2+ delivery to the injured spinal cord, compared
with that of MgSO4 alone. Here, we assessed spinal extracellular Mg2+ and
glutamate levels following SCI in rats using microdialysis. Basal levels of
extracellular Mg2+ (~0.5 mM) were significantly reduced to 0.15 mM in the core
and 0.12 mM in the rostral peri-lesion area after SCI. A single intravenous
infusion of saline or of MgSO4 at 192 MUmoL/kg did not significantly change
extracellular Mg2+ concentrations. However, a single infusion of AC105 (a MgCl2
in PEG) at an equimolar Mg2+ dose significantly increased the Mg2+ concentration
to 0.3 mM (core area) and 0.25 mM (rostral peri-lesion area). Moreover, multiple
AC105 treatments completely restored the depleted extracellular Mg2+
concentrations after SCI to levels in the uninjured spinal cord. Repeated MgSO4
infusions slightly increased the Mg2+ concentrations while saline infusion had no
effect. In addition, AC105 treatment significantly reduced extracellular
glutamate levels in the lesion center after SCI. These results indicate that
intravenous infusion of PEG-formulated Mg2+ normalized the Mg2+ homeostasis
following SCI and reduced potentially neurotoxic glutamate levels, consistent
with a neuroprotective mechanism of blocking excitotoxicity.
PMID- 27503054
TI - Polychlorinated biphenyls and organochlorine pesticides in River Brahmaputra from
the outer Himalayan Range and River Hooghly emptying into the Bay of Bengal:
Occurrence, sources and ecotoxicological risk assessment.
AB - River Brahmaputra (RB) from the outer Himalayan Range and River Hooghly (RH), a
distributary of River Ganga, are the two largest transboundary perennial rivers
supplying freshwater to the northeastern and eastern states of India. Given the
history of extensive usage of organochlorine pesticides and increasing
industrialization along the banks of these rivers we investigated selected
organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in the
surface water of River Brahmaputra and River Hooghly. Geomean of SigmaOCPs (53 ng
L-1) and Sigma19PCBs (108 ng L-1) was higher in RH compared with geomean of
SigmaOCPs (24 ng L-1) and Sigma19PCBs (77 ng L-1) in RB. Among OCPs, gamma-HCH
showed maximum detection frequency in both the rivers reflecting ongoing lindane
usage. DDT and endosulfan residues were observed at specific locations where past
or ongoing sources exist. Elevated concentrations of heavier congeners (penta
hepta) were observed in those sites along RH where port and industrial activities
were prevalent including informal electronic waste scrap processing units.
Furthermore along River Hooghly PCB-126 was high in the suburban industrial belt
of Howrah district. PCBs were found to be ubiquitously distributed in RB.
Atmospheric transport of tri- and tetra-PCB congeners from the primary source
regions might be a major contributor for PCBs in RB. Heavier congeners (penta
nona) in the urban centers of RB were likely due to industrial wastewater runoff
from the oil refineries in the Brahmaputra valley. Sigma19PCBs concentrations in
this study exceeded the USEPA recommended limit for freshwater. Ecotoxicological
risk assessment showed the possibility of adverse impact on the organisms in the
lower trophic level due to DDT and lindane contamination. Impact of endosulfan on
fishes might be of considerable concern for aquatic environment.
PMID- 27503055
TI - Changes of primary and secondary metabolites in barley plants exposed to CdO
nanoparticles.
AB - The environmental fate of airborne nanoparticles and their toxicity to plants is
not yet fully understood. Pot-grown barley plants with second leaves developed
were therefore exposed to CdO nanoparticles (CdONPs) of ecologically relevant
size (7-60 nm) and concentration (2.03 +/- 0.45 * 105 particles cm-3) in air for
3 weeks. An experiment was designed to test the effects of different treatments
when only leaves (T1); leaves and soil substrate (T2); and leaves, soil, and
water supply were exposed to nanoparticles (T3). A fourth, control group of
plants was left without treatment (T0). Although CdONPs were directly absorbed by
leaves from the air, a part of leaf-allocated Cd was also transported from roots
by transpiration flow. Chromatographic assays revealed that CdONPs had a
significant effect on total content of primary metabolites (amino acids and
saccharides) but no significant effect on total content of secondary metabolites
(phenolic compounds, Krebs cycle acids, and fatty acids). In addition, the
compositions of individual metabolite classes were affected by CdONP treatment.
For example, tryptophan and phenylalanine were the most affected amino acids in
both analysed organs, while ferulic acid and isovitexin constituted the
polyphenols most affected in leaves. Even though CdONP treatment had no effect on
total fatty acids content, there were significant changes in the composition of
saturated and unsaturated fatty acids in both the roots and leaves of treated
plants. Although the results indicate the most pronounced effect in T3 plants as
compared to T1 and T2 plants, even just leaf exposure to CdONPs has the potential
to induce changes in plant metabolism.
PMID- 27503056
TI - Serum POP concentrations are highly predictive of inner blubber concentrations at
two extremes of body condition in northern elephant seals.
AB - Long-lived, upper trophic level marine mammals are vulnerable to bioaccumulation
of persistent organic pollutants (POPs). Internal tissues may accumulate and
mobilize POP compounds at different rates related to the body condition of the
animal and the chemical characteristics of individual POP compounds; however,
collection of samples from multiple tissues is a major challenge to ecotoxicology
studies of free-ranging marine mammals and the ability to predict POP
concentrations in one tissue from another tissue remains rare. Northern elephant
seals (Mirounga angustirostris) forage on mesopelagic fish and squid for months
at a time in the northeastern Pacific Ocean, interspersed with two periods of
fasting on land, which results in dramatic seasonal fluctuations in body
condition. Using northern elephant seals, we examined commonly studied tissues in
mammalian toxicology to describe relationships and determine predictive equations
among tissues for a suite of POP compounds, including SigmaDDTs, SigmaPCBs,
Sigmachlordanes, and SigmaPBDEs. We collected paired blubber (inner and outer)
and blood serum samples from adult female and male seals in 2012 and 2013 at Ano
Nuevo State Reserve (California, USA). For females (N = 24), we sampled the same
seals before (late in molting fast) and after (early in breeding fast) their
approximately seven month foraging trip. For males, we sampled different seals
before (N = 14) and after (N = 15) their approximately four month foraging trip.
We observed strong relationships among tissues for many, but not all compounds.
Serum POP concentrations were strong predictors of inner blubber POP
concentrations for both females and males, while serum was a more consistent
predictor of outer blubber for males than females. The ability to estimate POP
blubber concentrations from serum, or vice versa, has the potential to enhance
toxicological assessment and physiological modeling. Furthermore, predictive
equations may illuminate commonalities or distinctions in bioaccumulation across
marine mammal species.
PMID- 27503058
TI - Increase in moped injuries requiring emergency care.
AB - BACKGROUND: There has been a marked increased in moped use over the past few
years. In addition, there has been an increase in moped-related injuries
presenting to the emergency department (ED). The objective of this study is to
characterize moped-related injuries presenting to US EDs and obtain national
estimates of moped injury incidence over time. METHODS: Data regarding moped
injuries were queried from the National Electronic Injury Surveillance System
from calendar year 2007 to 2015. Data included diagnosis, body part injured, ED
disposition, and patient demographics. RESULTS: There were an estimated 114 729
moped-related injuries treated in US EDs from 2007 to 2015 (95% confidence
interval, 102 156-127 302). In addition, there was an increase in the number of
moped injuries annually (B = 762.1, P < .01). The average number of moped
injuries yearly was 12 748. The mean age was 34 years. Patients between ages 19
and 38 years represented 42% of the study population. Men (74%) and whites (55%)
accounted for most of the injured population. Most injuries were stabilized in
the ED and discharged home (85%). Approximately 9% of injuries were admitted to
the hospital, and fractures constituted 59% of all diagnoses admitted to the
hospital. Contusions (27%) and fractures (24%) accounted for most diagnoses. The
most common body part injured was the head (16%). CONCLUSIONS: Moped injuries
have increased since 2007 and mopeds are associated with severe injuries.
Education and reexamination of current moped laws may decrease the number and
severity of moped-related injuries.
PMID- 27503057
TI - Neutron Scattering Studies of the Interplay of Amyloid beta Peptide(1-40) and An
Anionic Lipid 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol.
AB - The interaction between lipid bilayers and Amyloid beta peptide (Abeta) plays a
critical role in proliferation of Alzheimer's disease (AD). AD is expected to
affect one in every 85 humans by 2050, and therefore, deciphering the interplay
of Abeta and lipid bilayers at the molecular level is of profound importance. In
this work, we applied an array of neutron scattering methods to study the
structure and dynamics of Abeta(1-40) interacting 1,2-dimyristoyl-sn-glycero-3
phosphoglycerol (DMPG) bilayers. In the structural investigations of lipid
bilayer's response to Abeta binding, Small Angle Neutron Scattering and Neutron
Membrane Diffraction revealed that the Abeta anchors firmly to the highly charged
DMPG bilayers in the interfacial region between water and hydrocarbon chain, and
it doesn't penetrate deeply into the bilayer. This association mode is
substantiated by the dynamics studies with high resolution Quasi-Elastic Neutron
Scattering experiments, showing that the addition of Abeta mainly affects the
slower lateral motion of lipid molecules, especially in the fluid phase, but not
the faster internal motion. The results revealed that Abeta associates with the
highly charged membrane in surface with limited impact on the structure, but the
altered membrane dynamics could have more influence on other membrane processes.
PMID- 27503059
TI - Application of nitroglycerin patch to treat finger cyanosis due to unintentional
injection of epinephrine.
PMID- 27503060
TI - Pharmacist impact on time to antibiotic administration in patients with sepsis in
an ED.
AB - PURPOSE: The purpose was to determine if the physical presence of a clinical
pharmacist in the emergency department (ED) would decrease antibiotic order to
administration time in adult patients with sepsis, severe sepsis, or septic
shock. METHODS: We conducted a retrospective review of adult patients presenting
to the ED between January and December 2014 with a diagnosis of sepsis, severe
sepsis, or septic shock who required intravenous antibiotics. RESULTS: A total of
186 patients (92 patients when an ED pharmacist was present and 94 when no ED
pharmacist was present) were included in the analysis. Baseline characteristics
were similar between groups. When a pharmacist was present, patients received
antibiotics sooner (median 0.61 vs 0.88 hour, P=.001), Surviving Sepsis Campaign
goals for antibiotic administration time were more likely to be met (88% vs 72%,
P=.0097), and initial antibiotics were appropriate more often (97% vs 81%,
P=.0008). No significant differences were noted in intensive care unit length of
stay, hospital length of stay, ventilator days, or in-hospital mortality.
CONCLUSIONS: Physical presence of a clinical pharmacist in the ED decreased time
to administration and increased appropriateness of intravenous antibiotics for
adult patients with sepsis, severe sepsis, or septic shock.
PMID- 27503061
TI - The role of prehospital advanced airway management on outcomes for out-of
hospital cardiac arrest patients: a meta-analysis.
AB - OBJECTIVE: The objective of this meta-analysis was to compare the benefits of
prehospital advanced airway management (AAM) and basic airway management (BAM)
for out-of-hospital cardiac arrest (OHCA) patients. METHODS: Two investigators
performed a systematic review of PubMed, EMBASE, and the Cochrane Database to
identify all peer-reviewed articles relevant to this meta-analysis. We included
all articles describing emergency medical system-treated nontraumatic OHCAs;
specifically, all articles that described intervention of the prehospital AAM
type were considered. The primary outcome was survival to discharge, whereas the
secondary outcome was neurologic recovery after an OHCA event. For subgroup
analysis, we compared the clinical outcome of endotracheal intubation (ETI), a
specific type of AAM, vs BAM. RESULTS: We reviewed 1452 studies, 10 of which
satisfied all the inclusion criteria and involved 17 380 patients subjected to
AAM and 67 525 subjected to BAM. Based on the full random effects model, patients
who received AAM had lower odds of survival (odds ratio [OR], 0.51; 95%
confidence interval [CI], 0.29-0.90) compared with BAM. Subgroup analysis for ETI
vs BAM showed no significant association with respect to survival (OR, 0.44; 95%
CI, 0.16-1.23). There were no significant differences in the odds of neurologic
recovery between AAM and BAM (OR, 0.64; 95% CI, 0.03-1.37). CONCLUSIONS: Our
results reveal decreased survival odds for OHCA patients treated with AAM by
emergency medical service personnel compared with BAM. However, the role of
prehospital AAM, especially ETI, on achieving neurologic recovery remains
unclear.
PMID- 27503062
TI - A survival case of tension gastrothorax due to hiatal hernia, the key of life
saving is thoracotomy.
PMID- 27503063
TI - Severe diabetic ketoacidosis presenting with negative serum ketones.
PMID- 27503064
TI - A dramatic case of malignant atrophic papulosis (Kohlmeier-Degos disease) with
fatal outcome.
PMID- 27503065
TI - Severe respiratory disease with rhinovirus detection: Role of bacteria in the
most severe cases.
PMID- 27503066
TI - An expedient reverse-phase high-performance chromatography (RP-HPLC) based method
for high-throughput analysis of deferoxamine and ferrioxamine in urine.
AB - The present study was planned to optimize and validate an expedient reverse-phase
high chromatography (RP-HPLC) based protocol for the analysis of deferoxamine
(DFO) and ferrioxamine (FO) in urinary execration of patients suffering beta
thalassemia major. The optimized RP-HPLC method was found to be linear over the
wide range of DFO and FO concentration (1-90 MUg/mL) with appreciable recovery
rates (79.64-97.30%) of quality controls at improved detection and quantitation
limits and acceptable inter and intraday variability. Real-time analysis of DFO
and FO in the urine of thalassemic patients (male and female) at different
intervals of Desferal(r)(Novartis Pharmaceuticals Corporation) injection revealed
DFO and FO excretion at significantly (p < 0) different rates. The maximum
concentrations of DFO (76.7 +/- 3.06 MUg/mL) and FO (74.2 +/- 3.25 MUg/mL) were
found in urine samples, collected after 6 h of drug infusion while the minimum
levels of DFO (1.10 +/- 0.12 MUg/mL) and FO (2.97 +/- 0.13 MUg/mL) were excreted
by patients after 24 h. The present paper offers balanced conditions for an
expedient, reliable and quick determination of DFO and FO in urine samples.
PMID- 27503067
TI - Palliative Care and Cardiovascular Disease and Stroke: A Policy Statement From
the American Heart Association/American Stroke Association.
AB - The mission of the American Heart Association/American Stroke Association
includes increasing access to high-quality, evidence-based care that improves
patient outcomes such as health-related quality of life and is consistent with
the patients' values, preferences, and goals. Awareness of and access to
palliative care interventions align with the American Heart Association/American
Stroke Association mission. The purposes of this policy statement are to provide
background on the importance of palliative care as it pertains to patients with
advanced cardiovascular disease and stroke and their families and to make
recommendations for policy decisions. Palliative care, defined as patient- and
family-centered care that optimizes health-related quality of life by
anticipating, preventing, and treating suffering, should be integrated into the
care of all patients with advanced cardiovascular disease and stroke early in the
disease trajectory. Palliative care focuses on communication, shared decision
making about treatment options, advance care planning, and attention to physical,
emotional, spiritual, and psychological distress with inclusion of the patient's
family and care system. Our policy recommendations address the following:
reimbursement for comprehensive delivery of palliative care services for patients
with advanced cardiovascular disease and stroke; strong payer-provider
relationships that involve data sharing to identify patients in need of
palliative care, identification of better care and payment models, and
establishment of quality standards and outcome measurements; healthcare system
policies for the provision of comprehensive palliative care services during
hospitalization, including goals of care, treatment decisions, needs of family
caregivers, and transition to other care settings; and health professional
education in palliative care as part of licensure requirements.
PMID- 27503068
TI - Prospective evaluation of SeptiFast Multiplex PCR in children with systemic
inflammatory response syndrome under antibiotic treatment.
AB - BACKGROUND: Antimicrobially pre-treated children with systemic inflammation often
pose a diagnostic challenge to the physician. We aimed to evaluate the additional
use of SeptiFast multiplex polymerase chain reaction (PCR) to identify causative
pathogens in children with suspected systemic bacterial or fungal infection.
METHODS: Prospective observational study in 39 children with systemic
inflammatory response syndrome (SIRS) under empiric antibiotic treatment. Primary
outcome was the rate of positive blood cultures (BC), compared to the rate of
positive SeptiFast (SF) results. RESULTS: In total, 14 SF-samples yielded
positive results, compared to 4 positive BC (p < 0.05). All blood cultures and 13
of 14 positive SF-tests were considered infection. Median time for positive BC
was 2 days, and time to definite result was 6 days, compared to 12 h for SF.
Antimicrobial therapy was adapted in 7 of the 14 patients with positive
SeptiFast, and in 3 of the 4 patients with positive BC. Best predictive power for
positive SF shown by receiver-operating characteristic was demonstrated for
procalcitonin PCT (Area under the curve AUC: 0.79), compared to C-reactive
protein CRP (AUC: 0.51) and leukocyte count (AUC: 0.46). A procalcitonin
threshold of 0.89 ng/ml yielded a sensitivity of 0.82 and a specifity of 0.7.
Children with a positive SeptiFast result on day 0 had a significantly higher
risk to require treatment on the Pediatric Intensive Care Unit or to be deceased
on day 30 (Odds-Ratio 8.62 (CI 1.44-51.72). CONCLUSIONS: The additional testing
with SeptiFast in antimicrobially pre-treated children with systemic inflammation
enhances the rate of pathogen detection. The influence of multiplex PCR on
clinically relevant outcome parameters has to be further evaluated. ( TRIAL
REGISTRATION: DRKS00004694).
PMID- 27503069
TI - Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II
expression in thymic epithelium and CD4 T cell selection.
AB - Major histocompatibility complex class II (MHC II) expression is tightly
regulated, being subjected to cell type-specific mechanisms that closely control
its levels at the cell surface. Ubiquitination by the E3 ubiquitin ligase MARCH 1
regulates MHC II expression in dendritic cells and B cells. In this study, we
demonstrate that the related ligase MARCH 8 is responsible for regulating surface
MHC II in thymic epithelial cells (TECs). March8(-/-) mice have elevated MHC II
at the surface of cortical TECs and autoimmune regulator (AIRE)(-) medullary TECs
(mTECs), but not AIRE(+) mTECs. Despite this, thymic and splenic CD4(+) T cell
numbers and repertoires remained unaltered in March8(-/-) mice. Notably, the
ubiquitination of MHC II by MARCH 8 is controlled by CD83. Mice expressing a
mutated form of CD83 (Cd83(anu/anu) mice) have impaired CD4(+) T cell selection,
but deleting March8 in Cd83(anu/anu) mice restored CD4(+) T cell selection to
normal levels. Therefore, orchestrated regulation of MHC II surface expression in
TECs by MARCH 8 and CD83 plays a major role in CD4(+) T cell selection. Our
results also highlight the specialized use of ubiquitinating machinery in
distinct antigen-presenting cell types, with important functional consequences
and implications for therapeutic manipulation.
PMID- 27503070
TI - Multiple allogeneic progenitors in combination function as a unit to support
early transient hematopoiesis in transplantation.
AB - Cord blood (CB) is a valuable donor source in hematopoietic cell transplantation.
However, the initial time to engraftment in CB transplantation (CBT) is often
delayed because of low graft cell numbers. This limits the use of CB. To overcome
this cell dose barrier, we modeled an insufficient dose CBT setting in lethally
irradiated mice and then added hematopoietic stem/progenitor cells (HSCs/HPCs;
HSPCs) derived from four mouse allogeneic strains. The mixture of HSPCs rescued
recipients and significantly accelerated hematopoietic recovery. Including T
cells from one strain favored single-donor chimerism through graft versus graft
reactions, with early hematopoietic recovery unaffected. Furthermore, using
clinically relevant procedures, we successfully isolated a mixture of CD34(+)
cells from multiple frozen CB units at one time regardless of HLA-type
disparities. These CD34(+) cells in combination proved transplantable into
immunodeficient mice. This work provides proof of concept that when circumstances
require support of hematopoiesis, combined multiple units of allogeneic HSPCs are
capable of early hematopoietic reconstitution while allowing single-donor
hematopoiesis by a principal graft.
PMID- 27503071
TI - Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII
turnover in cortical epithelial cells through CD83.
AB - Deficiency of CD83 in thymic epithelial cells (TECs) dramatically impairs thymic
CD4 T cell selection. CD83 can exert cell-intrinsic and -extrinsic functions
through discrete protein domains, but it remains unclear how CD83's capacity to
operate through these alternative functional modules relates to its crucial role
in TECs. In this study, using viral reconstitution of gene function in TECs, we
found that CD83's transmembrane domain is necessary and sufficient for thymic CD4
T cell selection. Moreover, a ubiquitination-resistant MHCII variant restored CD4
T cell selection in Cd83(-/-) mice. Although during dendritic cell maturation
CD83 is known to stabilize MHCII through opposing the ubiquitin ligase March1,
regulation of March1 did not account for CD83's TEC-intrinsic role. Instead, we
provide evidence that MHCII in cortical TECs (cTECs) is targeted by March8, an E3
ligase of as yet unknown physiological substrate specificity. Ablating March8 in
Cd83(-/-) mice restored CD4 T cell development. Our results identify CD83
mediated MHCII stabilization through antagonism of March8 as a novel functional
adaptation of cTECs for T cell selection. Furthermore, these findings suggest an
intriguing division of labor between March1 and March8 in controlling inducible
versus constitutive MHCII expression in hematopoietic antigen-presenting cells
versus TECs.
PMID- 27503072
TI - An activated form of ADAM10 is tumor selective and regulates cancer stem-like
cells and tumor growth.
AB - The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins,
including ligands and receptors of the Notch, Eph, and erbB families, thereby
activating signaling pathways critical for tumor initiation and maintenance.
ADAM10 is thus a promising therapeutic target. Although widely expressed, its
activity is normally tightly regulated. We now report prevalence of an active
form of ADAM10 in tumors compared with normal tissues, in mouse models and
humans, identified by our conformation-specific antibody mAb 8C7.
Structure/function experiments indicate mAb 8C7 binds an active conformation
dependent on disulfide isomerization and oxidative conditions, common in tumors.
Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch
signaling, known to mediate chemoresistance. Importantly, specific targeting of
active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models,
particularly regrowth after chemotherapy. Our results indicate targeted
inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor
development and drug resistance.
PMID- 27503073
TI - Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent
control of cytomegalovirus infection.
AB - The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved
in cellular adhesion and immune response. It engages the activating receptor DNAX
accessory molecule (DNAM)-1, the inhibitory receptor TIGIT, and the CD96 receptor
with both activating and inhibitory functions. Human cytomegalovirus (HCMV) down
regulates PVR expression, but the significance of this viral function in vivo
remains unknown. Here, we demonstrate that mouse CMV (MCMV) also down-regulates
the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic
reticulum and promotes its degradation. A MCMV mutant lacking the PVR inhibitor
was attenuated in normal mice but not in mice lacking DNAM-1. This attenuation
was partially reversed by NK cell depletion, whereas the simultaneous depletion
of mononuclear phagocytes abolished the virus control. This effect was associated
with the increased expression of DNAM-1, whereas TIGIT and CD96 were absent on
these cells. An increased level of proinflammatory cytokines in sera of mice
infected with the virus lacking the m20.1 and an increased production of iNOS by
inflammatory monocytes was observed. Blocking of CCL2 or the inhibition of iNOS
significantly increased titer of the virus lacking m20.1. In this study, we have
demonstrated that inflammatory monocytes, together with NK cells, are essential
in the early control of CMV through the DNAM-1-PVR pathway.
PMID- 27503074
TI - Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1
dependent gene regulation and IFN-gamma-mediated host defenses.
AB - An early hallmark of Toxoplasma gondii infection is the rapid control of the
parasite population by a potent multifaceted innate immune response that engages
resident and homing immune cells along with pro- and counter-inflammatory
cytokines. In this context, IFN-gamma activates a variety of T. gondii-targeting
activities in immune and nonimmune cells but can also contribute to host immune
pathology. T. gondii has evolved mechanisms to timely counteract the host IFN
gamma defenses by interfering with the transcription of IFN-gamma-stimulated
genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional
activity) as a critical molecular switch that is secreted by intracellular
parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent
proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on
dedicated loci but also promotes shaping of a nonpermissive chromatin through its
capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional
repressor. We found that during mice acute infection, TgIST-deficient parasites
are rapidly eliminated by the homing Gr1(+) inflammatory monocytes, thus
highlighting the protective role of TgIST against IFN-gamma-mediated killing. By
uncovering TgIST functions, this study brings novel evidence on how T. gondii has
devised a molecular weapon of choice to take control over a ubiquitous immune
gene expression mechanism in metazoans, as a way to promote long-term parasitism.
PMID- 27503075
TI - Widespread transneuronal propagation of alpha-synucleinopathy triggered in
olfactory bulb mimics prodromal Parkinson's disease.
AB - Parkinson's disease (PD) is characterized by the progressive appearance of
intraneuronal Lewy aggregates, which are primarily composed of misfolded alpha
synuclein (alpha-syn). The aggregates are believed to propagate via neural
pathways following a stereotypical pattern, starting in the olfactory bulb (OB)
and gut. We hypothesized that injection of fibrillar alpha-syn into the OB of
wild-type mice would recreate the sequential progression of Lewy-like pathology,
while triggering olfactory deficits. We demonstrate that injected alpha-syn
fibrils recruit endogenous alpha-syn into pathological aggregates that spread
transneuronally over several months, initially in the olfactory network and later
in distant brain regions. The seeded inclusions contain posttranslationally
modified alpha-syn that is Thioflavin S positive, indicative of amyloid fibrils.
The spreading alpha-syn pathology induces progressive and specific olfactory
deficits. Thus, we demonstrate that propagating alpha-syn pathology triggered in
the OB is functionally detrimental. Collectively, we have created a mouse model
of prodromal PD.
PMID- 27503076
TI - Empirical monotherapy with meropenem or combination therapy: the microbiological
point of view.
AB - The increase in the number of clinical isolates of multiresistant
Enterobacteriaceae and Pseudomonas aeruginosa raises problems in decision-making
on empirical treatments for severe Gram-negative bacilli-associated infections.
The aim of our study is to determine the resistance of meropenem in our setting
and the co-resistance of a combination of this compound with two antibiotics from
different families: amikacin and ciprofloxacin. Between 2009 and 2013, a total of
81,310 clinical isolates belonging to the main species of Enterobacteriaceae and
39,191 clinical isolates of P. aeruginosa isolated in 28 hospitals in the
Valencian Community on the South East Mediterranean Coast of Spain were analyzed
using data provided by RedMiva (microbiological surveillance network of the
Valencian Community). Meropenem resistance in Enterobacteriaceae increased from
0.16 % in 2009 to 1.25 % in 2013. Very few Enterobacteriaceae strains resistant
to meropenem were sensitive to ciprofloxacin; in contrast, the combination of
meropenem and amikacin led to a marked decrease in the risk of the microorganisms
being resistant to both drugs (RR = 34 in 2013). In the case of P. aeruginosa,
meropenem resistance also increased (from 14.32 % in 2009 to 24.52 % in 2013).
Most meropenem-resistant P. aeruginosa isolates were also resistant to
fluoroquinolones. However, the addition of amikacin led to a more than three-fold
decrease in the risk of resistance. In our setting, empirical treatment with
meropenem is adequate in enterobacterial infections, but poses difficulties when
infection due to P. aeruginosa is suspected, in which case a combination of
meropenem and amikacin has been shown to have a higher microbiological success
rate.
PMID- 27503077
TI - Large-Scale medical image analytics: Recent methodologies, applications and
Future directions.
AB - Despite the ever-increasing amount and complexity of annotated medical image
data, the development of large-scale medical image analysis algorithms has not
kept pace with the need for methods that bridge the semantic gap between images
and diagnoses. The goal of this position paper is to discuss and explore
innovative and large-scale data science techniques in medical image analytics,
which will benefit clinical decision-making and facilitate efficient medical data
management. Particularly, we advocate that the scale of image retrieval systems
should be significantly increased at which interactive systems can be effective
for knowledge discovery in potentially large databases of medical images. For
clinical relevance, such systems should return results in real-time, incorporate
expert feedback, and be able to cope with the size, quality, and variety of the
medical images and their associated metadata for a particular domain. The design,
development, and testing of the such framework can significantly impact
interactive mining in medical image databases that are growing rapidly in size
and complexity and enable novel methods of analysis at much larger scales in an
efficient, integrated fashion.
PMID- 27503078
TI - Reflections on ultrasound image analysis.
AB - Ultrasound (US) image analysis has advanced considerably in twenty years.
Progress in ultrasound image analysis has always been fundamental to the
advancement of image-guided interventions research due to the real-time
acquisition capability of ultrasound and this has remained true over the two
decades. But in quantitative ultrasound image analysis - which takes US images
and turns them into more meaningful clinical information - thinking has perhaps
more fundamentally changed. From roots as a poor cousin to Computed Tomography
(CT) and Magnetic Resonance (MR) image analysis, both of which have richer
anatomical definition and thus were better suited to the earlier eras of medical
image analysis which were dominated by model-based methods, ultrasound image
analysis has now entered an exciting new era, assisted by advances in machine
learning and the growing clinical and commercial interest in employing low-cost
portable ultrasound devices outside traditional hospital-based clinical settings.
This short article provides a perspective on this change, and highlights some
challenges ahead and potential opportunities in ultrasound image analysis which
may both have high impact on healthcare delivery worldwide in the future but may
also, perhaps, take the subject further away from CT and MR image analysis
research with time.
PMID- 27503079
TI - 20th anniversary of the Medical Image Analysis journal (MedIA).
PMID- 27503080
TI - Quantitative analysis of retinal OCT.
AB - Clinical acceptance of 3-D OCT retinal imaging brought rapid development of
quantitative 3-D analysis of retinal layers, vasculature, retinal lesions as well
as facilitated new research in retinal diseases. One of the cornerstones of many
such analyses is segmentation and thickness quantification of retinal layers and
the choroid, with an inherently 3-D simultaneous multi-layer LOGISMOS (Layered
Optimal Graph Image Segmentation for Multiple Objects and Surfaces) segmentation
approach being extremely well suited for the task. Once retinal layers are
segmented, regional thickness, brightness, or texture-based indices of individual
layers can be easily determined and thus contribute to our understanding of
retinal or optic nerve head (ONH) disease processes and can be employed for
determination of disease status, treatment responses, visual function, etc. Out
of many applications, examples provided in this paper focus on image-guided
therapy and outcome prediction in age-related macular degeneration and on
assessing visual function from retinal layer structure in glaucoma.
PMID- 27503081
TI - Renal transplantation in human immunodeficiency virus-infected recipients: a case
control study from the Brazilian experience.
AB - BACKGROUND: Highly active antiretroviral therapy has turned human
immunodeficiency virus (HIV)-infected patients with end-stage renal disease into
suitable candidates for renal transplantation. We present the Brazilian
experience with kidney transplantation in HIV-infected recipients observed in a
multicenter study. METHODS: HIV-infected kidney transplant recipients and matched
controls were evaluated for the incidence of delayed graft function (DGF), acute
rejection (AR), infections, graft function, and survival of patients and renal
grafts. RESULTS: Fifty-three HIV-infected recipients and 106 controls were
enrolled. Baseline characteristics were similar, but a higher frequency of pre
transplant positivity for hepatitis C virus and cytomegalovirus infections was
found in the HIV group. Immunosuppressive regimens did not differ, but a trend
was observed toward lower use of anti-thymocyte globulin in the group of HIV
infected recipients (P = 0.079). The HIV-positive recipient group presented a
higher incidence of treated AR (P = 0.036) and DGF (P = 0.044). Chronic Kidney
Disease Epidemiology Collaboration estimated that glomerular filtration rate was
similar at 6 months (P = 0.374) and at 12 months (P = 0.957). The median number
of infections per patient was higher in the HIV-infected group (P = 0.018). The 1
year patient survival (P < 0.001) and graft survival (P = 0.004) were lower, but
acceptable, in the group of HIV-infected patients. CONCLUSIONS: In the Brazilian
experience, despite somewhat inferior outcomes, kidney transplantation is an
adequate therapy for selected HIV-infected recipients.
PMID- 27503082
TI - Patients' Perspective of Medication Adherence in Chronic Conditions: A
Qualitative Study.
AB - INTRODUCTION: About 50% of patients do not take their long-term therapy for
chronic conditions as prescribed. Many studies have centered on patients'
adherence to a specific treatment or single conditions, but few have taken all
chronic conditions into consideration from a patient's perspective. This study
aims to explore factors that impact on drug compliance and to identify strategies
to improve this from the perspective of patients with at least one chronic
condition. METHODS: Patients were recruited by healthcare professionals from a
hospital pharmacy, four community pharmacies, patient associations, and a primary
care center in Barcelona. Five focus groups were conducted (N = 36).
Conversations were audiotaped and transcribed verbatim to allow qualitative
analysis. RESULTS: Study subjects were aged 39-90 years (mean 65 years) and the
mean number of comorbidities per patient was 2.3 (range 1-7). The main modifiers
of therapeutic conduct were: patients' health beliefs, patient-prescriber
relationships, and patients' motivation and perception of illness control. Study
participants wanted greater participation in decision-making concerning their
health and increased education about their illness and medication. They also
wanted individualized healthcare that took their preferences and personal and
emotional issues into account. CONCLUSION: Our results highlight how the patient
prescriber's relationship and factors such as health beliefs, motivation and
perception of illness control impact on medication adherence in chronic patients.
Future interventions to optimize adherence to treatment should focus on shared
decision-making and more extensive health education. FUNDING: Celgene
Corporation.
PMID- 27503083
TI - A systematic review of the effects of low-frequency repetitive transcranial
magnetic stimulation on cognition.
AB - rTMS is increasingly used for a variety of neuropsychiatric conditions. There are
data to support 'fast' rTMS (>=10 Hz) having some positive effects on cognitive
functioning, but a dearth of research looking at any such effects of 'slow' rTMS.
This question is important as cognitive dysfunction accompanies many
neuropsychiatric conditions and neuromodulation that potentially enhances or
hinders such functioning has important clinical consequences. To determine
cognitive effects of slow (<=1 Hz) rTMS, a systematic review of randomized
control trials assayed cognition in neurological, psychiatric, and healthy
volunteer <=1 Hz rTMS paradigms. Both active (fast rTMS) and placebo comparators
were included. 497 Records were initially obtained; 20 met inclusion criteria for
evaluation. Four major categories emerged: mood disorders; psychotic disorders;
cerebrovascular accidents; and 'other' (PTSD, OCD, epilepsy, anxiety, and
tinnitus). Cognitive effects were measured across several domains: attention,
executive functioning, learning, and psychomotor speed. Variability of study
paradigms and reporting precluded meta-analytical analysis. No statistically
significant improvement or deterioration was consistently found in any cognitive
domain or illness category. These data support the overall safety of rTMS in not
adversely affecting cognitive functioning. There are some data indicating that
rTMS might have cognitive enhancing potential, but these are too limited at this
time to make any firm conclusions, and the literature is marked by considerable
heterogeneity in study parameters that hinder interpretation. Greater consensus
is required in future studies in cognitive markers, and particularly in reporting
of protocols. Future work should evaluate the effects of rTMS on cognitive
training.
PMID- 27503084
TI - Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio
in the cerebrospinal fluid in Parkinson's disease: historical overview and future
prospects.
AB - Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro
Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987,
we detected PREP activity in human cerebrospinal fluid (CSF) using highly
sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl
coumarin amide as a new synthetic substrate, and found a marked decrease in its
activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease
(PD) as compared with its level in control patients without neurological
diseases. In 2013, Hannula et al. found co-localization of PREP with alpha
synuclein in the postmortem PD brain. Several recent studies also suggest that
the level of PREP in the brain of PD patients may be related to dopamine (DA)
cell death via promotion of alpha-synuclein oligomerization and that inhibitors
of PREP may play a neuroprotective role in PD. Although the relationship between
another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II)
and dipeptidyl peptidase IV (DPP IV), and alpha-synuclein in the PD brain is not
yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was
significantly increased in PD patients. This review discusses the possibility of
PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.
PMID- 27503085
TI - [Extensive yellowish fundus changes in a 6-year-old child].
AB - We describe a 6-year-old, symptom-free girl presenting with a best corrected
visual acuity of 0.6 on both eyes. Clinically we found yellowish subretinal
lesions in the macula and around the vessel arcade without signs of vasculitis or
abnormal vessels in the angiography. Fundus autofluorescence was marked and SD
OCT showed subretinal hyperreflective masses. With the help of molecular genetics
we could make the diagnosis of an autosomal recessive bestrophinopathy (ARB). The
natural history over 22 months revealed a slight recovery of the visual acuity as
well as a slight reduction of the subretinal deposits.
PMID- 27503087
TI - Urogynecology digest : Presented by Katie Propst.
PMID- 27503088
TI - Vaginal hysterectomy, vaginal salpingoophorectomy and uterosacral ligament
colpopexy: a view from above (in English and Spanish).
AB - AIM OF THE VIDEO: The aim of this video is to make vaginal hysterectomy (TVH),
vaginal salpingoophorectomy and uterosacral ligament (USL) colpopexy approachable
by showing the key procedural steps from both the vaginal and abdominal
perspectives. METHODS: This production shows TVH with salpingoophorectomy and USL
colpopexy that was performed on a cadaver and filmed simultaneously from the
vaginal and abdominal views. The video begins with an anatomy overview from the
open abdomen and proceeds with the TVH. The anterior and posterior peritoneal
entries, a technique to safely and easily access the adnexa, as well as the
placement of USL suspension sutures are highlighted. The proximity of the ureter
and its distance from the three locations most vulnerable to injury during this
procedure (the uterine artery pedicle, the infundibulopelvic ligament and the
USL) are illustrated. The location of the USL suspension sutures in relation to
the ischial spine, the rectum and the sacrum are demonstrated. For all of these
crucial steps, a series of picture-in-picture views simultaneously showing the
abdominal and vaginal perspectives are presented so that the viewer may better
understand the spatial anatomy. CONCLUSION: This video provides the viewer with a
unique anatomic perspective and helps more confidently perform TVH, vaginal
salpingooophorectomy and USL colpopexy.
PMID- 27503086
TI - Bioinformatic prediction of transcription factor binding sites at promoter
regions of genes for photoperiod and vernalization responses in model and
temperate cereal plants.
AB - BACKGROUND: Many genes involved in responses to photoperiod and vernalization
have been characterized or predicted in Arabidopsis (Arabidopsis thaliana),
Brachypodium (Brachypodium distachyon), wheat (Triticum aestivum) and barley
(Hordeum vulgare). However, little is known about the transcription regulation of
these genes, especially in the large, complex genomes of wheat and barley.
RESULTS: We identified 68, 60, 195 and 61 genes that are known or postulated to
control pathways of photoperiod (PH), vernalization (VE) and pathway integration
(PI) in Arabidopsis, Brachypodium, wheat and barley for predicting transcription
factor binding sites (TFBSs) in the promoters of these genes using the FIMO motif
search tool of the MEME Suite. The initial predicted TFBSs were filtered to
confirm the final numbers of predicted TFBSs to be 1066, 1379, 1528, and 789 in
Arabidopsis, Brachypodium, wheat and barley, respectively. These TFBSs were
mapped onto the PH, VE and PI pathways to infer about the regulation of gene
expression in Arabidopsis and cereal species. The GC contents in promoters,
untranslated regions (UTRs), coding sequences and introns were higher in the
three cereal species than those in Arabidopsis. The predicted TFBSs were most
abundant for two transcription factor (TF) families: MADS-box and CSD (cold shock
domain). The analysis of publicly available gene expression data showed that
genes with similar numbers of MADS-box and CSD TFBSs exhibited similar expression
patterns across several different tissues and developmental stages. The intra
specific Tajima D-statistics of TFBS motif diversity showed different binding
specificity among different TF families. The inter-specific Tajima D-statistics
suggested faster TFBS divergence in TFBSs than in coding sequences and introns.
Mapping TFBSs onto the PH, VE and PI pathways showed the predominance of MADS-box
and CSD TFBSs in most genes of the four species, and the difference in the
pathway regulations between Arabidopsis and the three cereal species. CONCLUSION:
Our approach to associating the key flowering genes with their potential TFs
through prediction of putative TFBSs provides a framework to explore regulatory
mechanisms of photoperiod and vernalization responses in flowering plants. The
predicted TFBSs in the promoters of the flowering genes provide a basis for
molecular characterization of transcription regulation in the large, complex
genomes of important crop species, wheat and barley.
PMID- 27503089
TI - Inhibitor treatment of peripheral mononuclear cells from Parkinson's disease
patients further validates LRRK2 dephosphorylation as a pharmacodynamic
biomarker.
AB - Activating mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly
associated with increased risk of Parkinson's disease (PD). Thus, LRRK2 kinase
inhibitors are in development as potential Parkinson's disease therapeutics. A
reduction in the constitutive levels of phosphorylation on leucine-rich repeat
kinase 2 (LRRK2) is currently used to measure target engagement of LRRK2 kinase
inhibitors in cell and animal models. We aimed to determine if reduced
phosphorylation of LRRK2 following inhibitor treatment is also a valid measure of
target engagement in peripheral mononuclear cells from Parkinson's disease
patients. Peripheral mononuclear cells from idiopathic Parkinson's disease
patients and controls were treated ex vivo with two structurally distinct
inhibitors of LRRK2, at four different doses, and immunoblotting was used to
assess the reduction in LRRK2 phosphorylation at Ser910, Ser935, Ser955 and
Ser973. Both inhibitors showed no acute toxicity in primary cells and both
inhibitors reduced the constitutive phosphorylation of LRRK2 at all measured
residues equally in both control and Parkinson's disease groups. Measuring the
reduction in LRRK2 phosphorylation resulting from LRRK2 kinase inhibition, is
thus a valid measure of acute peripheral target engagement in Parkinson's disease
patients. This is important if LRRK2 kinase inhibitors are to be used in a
clinical setting.
PMID- 27503091
TI - Safety Assessment of Liver Injury with Quetiapine Fumarate XR Management in Very
Heavy Drinking Alcohol-Dependent Patients.
AB - BACKGROUND: Studies have reported liver injury as a consequence of antipsychotic
treatment. Very heavy alcohol drinking (ten or more drinks/day for men and eight
for women) also causes liver injury. This study aims to evaluate liver injury
with quetiapine extended release (XR) in very heavy drinking alcohol-dependent
(AD) patients. METHODS: Two hundred and eighteen AD patients, 18-65 years of age,
received 12 weeks of quetiapine XR or placebo treatment in a dose-escalated
manner reaching the full dose of 400 mg/day during week 4. Blood chemistry and
hematology were assessed at baseline (W0), post-titration at the end of week 3
(W4), week 8 (W8), and end of week 12 (W13). Patients were further grouped as
GR.1 (no liver injury, ALT <=40) and GR.2 (pre-existing liver injury, ALT >40)
within each treatment. Drinking history, fasting blood glucose concentration
(FBG), and lipid panel were used as covariates in the analyses. RESULTS: Liver
injury and total drinks and average drinking measures from the Timeline follow
back questionnaire (TLFB) were highly associated. No significant exacerbation in
liver injury was observed in patients treated with quetiapine XR in GR.2. Liver
injury as determined by elevated alanine aminotransaminase (ALT) was reported in
a few patients in GR.1 who received quetiapine XR; however, the occurrence was
low, and the level of liver injury was not significant. FBG and lipid measures
showed some elevation, but did not show any significant association with liver
injury. CONCLUSION: Quetiapine XR did not show any significant exacerbation of
liver injury in very heavy drinking alcohol-dependent patients with pre-existing
liver injury. Frequency and severity of new liver injury cases in quetiapine XR
treated patients without any pre-existing liver injury was also low. Study
findings support medical management of AD patients with heavy drinking profile
using quetiapine XR formulation.
PMID- 27503092
TI - QTLs for earliness and yield-forming traits in the Lubuski * CamB barley RIL
population under various water regimes.
AB - Drought has become more frequent in Central Europe causing large losses in cereal
yields, especially of spring crops. The development of new varieties with
increased tolerance to drought is a key tool for improvement of agricultural
productivity. Material for the study consisted of 100 barley recombinant inbred
lines (RILs) (LCam) derived from the cross between Syrian and European parents.
The RILs and parental genotypes were examined in greenhouse experiments under
well-watered and water-deficit conditions. During vegetation the date of heading,
yield and yield-related traits were measured. RIL population was genotyped with
microsatellite and single nucleotide polymorphism markers. This population,
together with two other populations, was the basis for the consensus map
construction, which was used for identification of quantitative trait loci (QTLs)
affecting the traits. The studied lines showed a large variability in heading
date. It was noted that drought-treatment negatively affected the yield and its
components, especially when applied at the flag leaf stage. In total, 60 QTLs
were detected on all the barley chromosomes. The largest number of QTLs was found
on chromosome 2H. The main QTL associated with heading, located on chromosome 2H
(Q.HD.LC-2H), was identified at SNP marker 5880-2547, in the vicinity of Ppd-H1
gene. SNP 5880-2547 was also the closest marker to QTLs associated with plant
architecture, spike morphology and grain yield. The present study showed that the
earliness allele from the Syrian parent, as introduced into the genome of an
European variety could result in an improvement of barley yield performance under
drought conditions.
PMID- 27503090
TI - Solute Carriers in the Blood-Brain Barier: Safety in Abundance.
AB - Blood-brain barrier formed by brain capillary endothelial cells, being in contact
with astrocytes endfeet and pericytes, separates extracellular fluid from plasma.
Supply of necessary nutrients and removal of certain metabolites takes place due
to the activity of transporting proteins from ABC (ATP binding cassette) and SLC
(solute carrier) superfamilies. This review is focused on the SLC families
involved in transport though the blood-brain barrier of energetic substrates
(glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their
precursors, as well as organic ions. Members of SLC1, SLC2, SLC3/SLC7, SLC5,
SLC6, SLC16, SLC22, SLC38, SLC44, SLC47 and SLCO (SLC21), whose presence in the
blood-brain barriers has been demonstrated are characterized with a special
emphasis put on polarity of transporters localization in a luminal (blood side)
versus an abluminal (brain side) membrane.
PMID- 27503094
TI - Visualization of CSF Flow with Time-resolved 3D MR Velocity Mapping in Aqueductal
Stenosis Before and After Endoscopic Third Ventriculostomy : A Feasibility Study.
AB - PURPOSE: The aim of this study was to evaluate timed-resolved three-dimensional
(3D) magnetic resonance (MR) velocity mapping as a method for investigation of
cerebrospinal fluid (CSF) flow changes in patients with aqueductal stenosis (AS)
treated by endoscopic third ventriculostomy (ETV). METHODS: The MR velocity
mapping was performed in 12 AS patients before and after ETV and in 10 healthy
volunteers by using a 3-Tesla MR system. Time-resolved 3D MR velocity mapping
data were acquired with a standard 3D phase contrast (PC) sequence with cardiac
triggering. Values of mean (vmean) and maximum (vpeak) velocity were measured at
several ventricular structures using dedicated software. RESULTS: Of the patients
11 showed a satisfactory clinical improvement after ETV, whereas one patient
needed subsequent shunt implantation. All AS patients showed significant
hypomotile CSF flow dynamics in the third ventricle when compared to healthy
subjects before surgery (p < 0.05). In contrast, CSF flow velocity was increased
within the Foramen of Monro in AS patients. After ETV, all AS patients showed a
decrease of CSF flow dynamics within the third ventricle. Mean and peak CSF flow
velocities through the ventriculostomy were 1.72 +/- 0.59 cm/s (vmean) and 3.53
+/- 0.79 cm/s (vpeak), respectively after ETV. The patient who needed shunt
implantation after ETV had the lowest flow velocities through the
ventriculostomy. CONCLUSION: This study demonstrates that timed-resolved 3D MR
velocity mapping is a useful imaging investigation for diagnostics and follow-up
in patients with AS. This new technique provides an insight into the
physiological CSF flow changes related with AS and its treatment.
PMID- 27503095
TI - Improving knowledge and behaviours related to the cause, transmission and
prevention of Tuberculosis and early case detection: a descriptive study of
community led Tuberculosis program in Flores, Indonesia.
AB - BACKGROUND: The community's awareness of Tuberculosis (TB) and delays in health
care seeking remain important issues in Indonesia despite the extensive efforts
of community-based TB programs delivered by a non-government organisation (NGO).
This study explored the knowledge and behaviours in relation to TB and early
diagnosis before and after an asset-based intervention designed to improve these
issues. METHODS: Six villages in Flores, Indonesia were purposively selected to
participate in this study. Three villages served as intervention villages and the
other three villages provided a comparison group. Data collection included
interviews, group discussions, observations, field notes and audit of records.
RESULTS: In total, 50 participants across six villages were interviewed and three
group discussions were conducted in the intervention villages supplemented by 1 -
5 h of observation during monthly visits. Overall, participants in all villages
had limited knowledge regarding the cause and transmission of TB before the
intervention. The delay in health seeking behaviour was mainly influenced by
ignorance of TB symptoms. Health care providers also contributed to delayed
diagnosis by ignoring the symptoms of TB suspects at the first visit and failing
to examine TB suspects with sputum tests. Stigmatisation of TB patients by the
community was reported, although this did not seem to be common. Early case
detection was less than 50 % in four of the six villages before the asset-based
intervention. Knowledge of TB improved after the intervention in the intervention
villages alongside improved education activities. Early case detection also
increased in the intervention villages following this intervention. The behaviour
changes related to prevention of TB were also obvious in the intervention
villages but not the comparison group. CONCLUSION: This small project
demonstrated that an asset-based intervention can result in positive changes in
community's knowledge and behaviour in relation to TB and early case detection. A
continuing education process is like to be required to maintain this outcome and
to reach a wider community. Promoting community involvement and local initiatives
and engaging health care providers were important elements in the community-based
TB program implemented.
PMID- 27503096
TI - Crossing technological frontiers in radioguided intervention.
PMID- 27503097
TI - Prodromal symptoms of Parkinson's disease: Implications for epidemiological
studies of disease etiology.
AB - In recent years, there has been a major shift in our understanding of the course
of Parkinson's disease (PD) from a disease of the brain to a disease of long
latency, characterized by the progressive emergence of multiple non-motor
symptoms, including hyposmia, constipation, depression, anxiety, rapid eye
movement (REM) sleep behavior disorder and excessive daytime sleepiness, as well
as subtle motor signs, before the typical motor signs appear. Epidemiological
studies have made major contributions by allowing better characterization of
subsequent PD risk in relation to non-motor symptoms. Such findings have profound
implications for the conduct of epidemiological studies examining risk and
protective factors in PD, and the interpretation of their findings. Given the
length of the prodromal period, reverse causation in particular is a major
concern with many reported associations. One striking feature of PD etiology,
compared with other diseases, is the presence of numerous inverse associations.
If these associations are truly causal, they would have major implications for
disease prevention and for slowing disease progression. However, whether these
associations are truly causal remains to be demonstrated in future studies.
Experimental studies play an important role by offering a better understanding of
the underlying mechanisms. Well-designed epidemiological studies using innovative
approaches will also be key in elucidating whether these intriguing associations
are causal or a consequence of reverse causation.
PMID- 27503093
TI - Strategies of targeting the extracellular domain of RON tyrosine kinase receptor
for cancer therapy and drug delivery.
AB - PURPOSE: Cancer is one of the most important life-threatening diseases in the
world. The current efforts to combat cancer are being focused on molecular
targeted therapies. The main purpose of such approaches is based on targeting
cancer cell-specific molecules to minimize toxicity for the normal cells. RON
(Recepteur d'Origine Nantais) tyrosine kinase receptor is one of the promising
targets in cancer-targeted therapy and drug delivery. METHODS: In this review, we
will summarize the available agents against extracellular domain of RON with
potential antitumor activities. RESULTS: The presented antibodies and antibody
drug conjugates against RON in this review showed wide spectrum of in vitro and
in vivo antitumor activities promising the hope for them entering the clinical
trials. CONCLUSION: Due to critical role of extracellular domain of RON in
receptor activation, the development of therapeutic agents against this region
could lead to fruitful outcome in cancer therapy.
PMID- 27503099
TI - Large soft-tissue masses in an adult patient with Gaucher disease.
AB - Extra-osseous masses are rarely seen in Gaucher disease. Here we present a case
of a 30-year-old patient with Gaucher disease type 3, receiving beta
glucocerebrosidase enzyme replacement therapy, who presented with slowly
enlarging masses along her back. There was no osseous extension seen on imaging.
Biopsy of the mass ultimately showed extensive soft tissue infiltration by
Gaucher cells. No other cases of soft-tissue masses of this extent have been
described in the literature, and therefore management remains unclear.
PMID- 27503098
TI - Hypnosis and movement disorders: State of the art and perspectives.
AB - INTRODUCTION: Hypnosis might represent an interesting complementary therapeutic
approach to movement disorders, as it takes into account not only symptoms, but
also well-being, and empowers patients to take a more active role in their
treatment. METHODS: Our review of the literature on the use of hypnosis to treat
movement disorders was done by systematically searching the PubMed database for
reports published between 1984 and November 2015. The following variables were
extracted from each selected paper: study design; sample size; type of movement
disorder; hypnotic procedure; treatment duration; and efficacy. RESULTS: Thirteen
papers were selected for detailed analysis. Most concerned tremor in Parkinson's
disease and tics in Gilles de la Tourette syndrome. Although promising, the data
were insufficient to allow conclusions to be drawn on the efficacy of hypnosis in
movement disorders or to recommend its use in this setting. CONCLUSION: Well
designed studies taking into account some specific methodological challenges are
needed to determine the possible therapeutic utility of hypnosis in movement
disorders. In addition to the potential benefits for such patients, hypnosis
might also be useful for studying the neuroanatomical and functional
underpinnings of normal and abnormal movements.
PMID- 27503101
TI - Correcting motion in multiplanar cardiac magnetic resonance images.
AB - BACKGROUND: Misalignment in cardiac magnetic resonance (CMR) images can adversely
affect three-dimensional left ventricle modelling and downstream quantitative
analysis. Currently, there are two types of approaches for dealing with
realignment and motion distortion problems, one image based and the other
geometry based. Image-based approaches are limited by the inherent non
homogeneity and anisotropy of CMR images. Geometry-based approaches rely on
idealized models and over-simplified assumptions. This study was motivated by the
need for a robust and effective approach for correcting motion related
distortions due to misalignment in CMR images. METHODS: A cine cardiac magnetic
resonance image sequence was acquired using our routine clinical imaging
protocol. The left ventricular endocardium was delineated manually with software
assistance on all long and short-axis images. Long and short-axis contours were
projected onto a patient-based coordinate system and then realigned using
iterative registration. The realigned contour points were used to reconstruct the
shape of the left ventricle for quantitative validation. RESULTS: The method was
tested on five myocardial infarction patients whose images showed substantial
misalignment. Realignment time was about 16 seconds per case, using a 2.5 GHz CPU
desktop with obvious elimination of the distortion in the reconstructed model.
Using the long-axis contour as a reference in evaluating the reconstructed
models, it was apparent that the models with realigned contours had better
accuracy than the non-realigned ones. CONCLUSION: This study presents a novel,
geometry-based method for correcting motion distortions in CMR images. The method
incorporates (1) manual delineation, (2) registration based on a generalized,
iterative closest point algorithm, and (3) reconstruction of the shape of the
left ventricle for quantitative validation. The effectiveness of our approach is
corroborated both visually and by quantitative assessment. We envision the use of
our method in current clinical practice as a means of improving accuracy in the
evaluation of cardiac function.
PMID- 27503102
TI - Does chronic exposure to high levels of nitrogen dioxide exacerbate the short
term effects of airborne particles?
AB - BACKGROUND: Long-term exposure to air pollutants has been hypothesised as a
factor in susceptibility to short-term exposure to particulate matter (PM), but
results are not coherent. We studied the short-term effects of PM10 on mortality
and assessed whether long-term exposure to nitrogen dioxide (NO2) modifies this
association. METHODS: We used a case-crossover design to evaluate daily PM10
related mortality among 124 432 35+ year-old participants who died in Rome
between 2001 and 2010 and maintained the same address for at least 5 years before
death. Modification of PM10-related mortality by long-term NO2 exposure was
determined by two-way interaction, while a three-way interaction was used to
assess effect modification of high NO2 levels in population groups defined by
sociodemographic position and pre-existing diseases. RESULTS: Mortality increased
by 0.82% (0.23-1.41%) for each 10 ug/m3 increase in PM10. Mortality rose by 1.22%
(0.17-2.38%) in participants exposed to NO2 levels >=50 ug/m3 and by 0.69% (0.03
1.34%) in those exposed to levels <50 ug/m3 with no effect modification (p
interaction 0.378). A suggestion of effect modification was seen in 85+-year-olds
(3.10%; p-interaction 0.043), as well as in those with a pre-existing arrhythmia
(3.26%; p-interaction 0.014) and chronic obstructive pulmonary disease (3.52%; p
interaction 0.042). CONCLUSIONS: Long-term exposure to NO2 is not likely to
induce susceptibility to short-term PM10 exposure in the overall population.
However, an effect modification of NO2 is probable in the elderly and in those
suffering from arrhythmias and chronic obstructive pulmonary disease.
PMID- 27503103
TI - An Integrative Review of the Quality and Outcomes of Diabetes Education Programs
for Children and Adolescents.
AB - PURPOSE: The purpose of this study was twofold: (1) to describe the content of
recent diabetes education programs and their outcomes in terms of glycemic
control, disease management, and psychosocial criteria for children and
adolescents with type 1 diabetes and (2) to gauge the match between these
programs and the recommendations of the International Society for Pediatric and
Adolescent Diabetes (ISPAD). METHODS: The integrative review was carried out
according to the Cochrane recommendations. Thirteen databases were searched for
evaluations of education programs published from 2009 to 2014. Program
characteristics and outcomes were described. Quality of studies was assessed, and
program match with ISPAD recommendations was gauged. RESULTS: Of 2528 studies
found, 43 covering 36 education programs intended for youth with type 1 diabetes
were retained for review. Nine of these centered on self-care competencies, 18 on
psychosocial competencies, and 9 on both types of competency (mixed program).
Programs varied widely in terms of organization, procedure, and content. Glycemic
control was an indicator assessed in the majority of programs, but only half of
these (for the most part, self-care programs) reported positive findings in this
regard. Few programs seemed to affect psychosocial indicators. An online mixed
program, which was the program that best met the ISPAD recommendations, proved to
have an influence on glycemic control and several psychosocial criteria.
CONCLUSIONS: Various avenues can be considered to improve participant engagement
in education programs and to align these programs more closely with international
recommendations. Further research is required to enhance knowledge in this field.
PMID- 27503104
TI - Polymorphism of the 3'-UTR of the dopamine transporter gene (DAT) in New World
monkeys.
AB - Genetic polymorphism in the 3'-untranslated region (3'-UTR) of the dopamine
transporter (DAT) gene has been reported in both human and nonhuman primates, and
the variable number of tandem repeats (VNTR) polymorphism has been related to
several neurological and psychiatric disorders. As New World primates have been
employed as models in biomedical research in these fields, in the present study
we assessed genetic variation in the DAT gene in 25 robust capuchin monkeys
(Sapajus spp.) and 39 common marmosets (Callithrix jacchus). Using enzymatic
amplification followed by sequencing of amplified fragments, a VNTR polymorphism
in the 3'-UTR region of the DAT gene was identified in both robust capuchins and
common marmosets. The polymorphic tandem repeat of 40-bp basic units is similar
to the human VNTR consensus sequence, with size variants composed of 9, 10, and
11 units in marmosets and 8, 9, 13, and 17 basic units in capuchins. We found
behavioral evidence that carrying the 10-repeat DAT allele promotes flexible
choice and maximization of foraging in marmosets tested in an operant choice
paradigm. Moreover, in an intertemporal choice task, capuchins with longer repeat
variants show less self-controlled choices than capuchins with at least one short
repeat variant. Future research should focus on the relationship between these
DAT polymorphisms, dopamine reuptake via the dopamine transporter, and behavioral
and cognitive variation across New World monkey individuals.
PMID- 27503105
TI - The Contribution of the C-Terminal Tails of Microtubules in Altering the Force
Production Specifications of Multiple Kinesin-1.
AB - The extent to which beta tubulin isotypes contribute to the function of
microtubules and the microtubule-driven transport of molecular motors is poorly
understood. The major differences in these isotypes are associated with the
structure of their C-terminal tails. Recent studies have revealed a few aspects
of the C-terminal tails' regulatory role on the activities of some of the motor
proteins on a single-molecule level. However, little attention is given to the
degree to which the function of a team of motor proteins can be altered by the
microtubule's tail. In a set of parallel experiments, we investigated this open
question by studying the force production of several kinesin-1 (kinesin)
molecular motors along two groups of microtubules: regular ones and those
microtubules whose C-terminals are cleaved by subtilisin digestion. The results
indicate that the difference between the average of the force production of
motors along two types of microtubules is statistically significant. The
underlying mechanism of such production is substantially different as well. As
compared to untreated microtubules, the magnitude of the binding time of several
kinesin-1 is almost three times greater along subtilisin-treated microtubules.
Also, the velocity of the group of kinesin molecules shows a higher sensitivity
to external loads and reduces significantly under higher loads along subtilisin
treated microtubules. Together, this work shows the capacity of the tails in fine
tuning the force production characteristics of several kinesin molecules.
PMID- 27503106
TI - Dual targeting of Hsp90 in childhood acute lymphoblastic leukaemia.
PMID- 27503107
TI - Determining Survey Satisficing of Online Longitudinal Survey Data in the
Multicenter AIDS Cohort Study: A Group-Based Trajectory Analysis.
AB - BACKGROUND: Survey satisficing occurs when participants respond to survey
questions rapidly without carefully reading or comprehending them. Studies have
demonstrated the occurrence of survey satisficing, which can degrade survey
quality, particularly in longitudinal studies. OBJECTIVE: The aim of this study
is to use a group-based trajectory analysis method to identify satisficers when
similar survey questions were asked periodically in a long-standing cohort, and
to examine factors associated with satisficing in the surveys having sensitive
human immunodeficiency virus (HIV)-related behavioral questions. METHODS:
Behavioral data were collected semiannually online at all four sites of the
Multicenter AIDS Cohort Study (MACS) from October 2008 through March 2013. Based
on the start and end times, and the word counts per variable, response speed
(word counts per second) for each participant visit was calculated. Two-step
group-based trajectory analyses of the response speed across 9 study visits were
performed to identify potential survey satisficing. Generalized linear models
with repeated measures were used to investigate the factors associated with
satisficing on HIV-related behavioral surveys. RESULTS: Among the total 2138 male
participants, the median baseline age was 51 years (interquartile range, 45-58);
most of the participants were non-Hispanic white (62.72%, 1341/2138) and college
graduates (46.59%, 996/2138), and half were HIV seropositive (50.00%, 1069/2138).
A total of 543 men (25.40%, 543/2138) were considered potential satisficers with
respect to their increased trajectory tendency of response speed. In the
multivariate analysis, being 10 years older at the baseline visit increased the
odds of satisficing by 44% (OR 1.44, 95% CI 1.27-1.62, P<.001). Compared with the
non-Hispanic white participants, non-Hispanic black participants were 122% more
likely to satisfice the HIV-related behavioral survey (OR 2.22, 95% CI 1.69-2.91,
P<.001), and 99% more likely to do so for the other race/ethnicity group (OR
1.99, 95% CI 1.39-2.83, P<.001). Participants with a high school degree or less
were 67% more likely to satisfice the survey (OR 1.67, 95% CI 1.26-2.21, P<.001)
compared with those with a college degree. Having more than one sex partner and
using more than one recreational drug reduced the odds of satisficing by 24% (OR
0.76, 95% CI 0.61-0.94, P=.013) and 28% (OR 0.72, 95% CI 0.55-0.93, P=.013),
respectively. No statistically significant association of HIV serostatus with
satisficing was observed. CONCLUSIONS: Using a group-based trajectory analysis
method, we could identify consistent satisficing on HIV-related behavioral
surveys among participants in the MACS, which was associated with being older,
being non-white, and having a lower education level; however, there was no
significant difference by HIV serostatus. Methods to minimize satisficing using
longitudinal survey data are warranted.
PMID- 27503109
TI - No effect of juvenile hormone on task performance in a bumblebee (Bombus
terrestris) supports an evolutionary link between endocrine signaling and social
complexity.
AB - A hallmark of insect societies is a division of labor among workers specializing
in different tasks. In bumblebees the division of labor is related to body size;
relatively small workers are more likely to stay inside the nest and tend
("nurse") brood, whereas their larger sisters are more likely to forage. Despite
their ecological and economic importance, very little is known about the
endocrine regulation of division of labor in bumblebees. We studied the influence
of juvenile hormone (JH) on task performance in the bumblebee Bombus terrestris.
We first used a radioimmunoassay to measure circulating JH titers in workers
specializing in nursing and foraging activities. Next, we developed new protocols
for manipulating JH titers by combining a size-adjusted topical treatment with
the allatotoxin Precocene-I and replacement therapy with JH-III. Finally, we used
this protocol to test the influence of JH on task performance. JH levels were
either similar for nurses and foragers (three colonies), or higher in nurses (two
colonies). Nurses had better developed ovaries and JH levels were typically
positively correlated with ovarian state. Manipulation of JH titers influenced
ovarian development and wax secretion, consistent with earlier allatectomy
studies. These manipulations however, did not affect nursing or foraging
activity, or the likelihood to specialize in nursing or foraging activity. These
findings contrast with honeybees in which JH influences age-related division of
labor but not adult female fertility. Thus, the evolution of complex societies in
bees was associated with modifications in the way JH influences social behavior.
PMID- 27503108
TI - Association of affective temperaments with blood pressure and arterial stiffness
in hypertensive patients: a cross-sectional study.
AB - BACKGROUND: Affective temperaments (anxious, depressive, cyclothymic, irritable
and hyperthymic) measure subclinical manifestations of major mood disorders.
Furthermore, cumulating evidence suggests their involvement in somatic disorders
as well. We aimed to assess associations between affective temperament scores and
blood pressure and arterial stiffness parameters in hypertensive patients.
METHODS: In this cross-sectional study, 173 patients with well-controlled or
grade 1 chronic hypertension, with no history of depression, completed the TEMPS
A, Beck Depression Inventory (BDI) and Hamilton Anxiety Scale (HAM-A)
questionnaires in three GP practices. Arterial stiffness was measured with
tonometry (PulsePen). RESULTS: According to multiple linear regression analysis,
cyclothymic temperament score was positively associated with brachial systolic
blood pressure independently of age, sex, total cholesterol, brachial diastolic
blood pressure, BDI, HAM-A and the use of alprazolam (beta = 0.529, p = 0.042),
while hyperthymic temperament score was negatively related to augmentation index
independent of age, sex, smoking, heart rate, BDI, HAM-A and the use of
alprazolam (beta = -0.612, p = 0.013). A significant interaction was found
between cyclothymic temperament score and sex in predicting brachial systolic
blood pressure (p = 0.025), between irritable and anxious temperament scores and
sex in predicting pulse wave velocity (p = 0.021, p = 0.023, respectively) and an
interaction with borderline significance between hyperthymic temperament score
and sex in predicting augmentation index (p = 0.052). CONCLUSIONS: The present
findings highlight elevated blood pressure among subjects with high cyclothymic
temperament as well as an increased level of arterial stiffening in subjects with
low hyperthymic scores suggesting that affective temperaments may play a role in
the development of hypertension and arterial stiffening and may thus represent
markers of cardiovascular risk. Sex differences were also present in these
associations.
PMID- 27503111
TI - The analysis of scalp irritation by coacervates produced in hair shampoo via FTIR
with focal plane array detector, X-ray photoelectron microscopy and HaCaT cells.
AB - OBJECTIVE: Coacervates are inevitably formed on scalp on using hair washing
products. Our goal was to analyse the coacervates in detail to identify the part
responsible for scalp stimulation. METHODS: Shampoo that increases coacervate
formation was applied to in vitro skin and was washed. The residue was then
analysed using Fourier transform infrared spectroscopy-focal plane array (FTIR
FPA) and X-ray photoelectron microscopy (XPS). And HaCaT cells were used for
irritant test of coacervate. RESULTS: Through this research, it was confirmed
that the coacervate was a macromolecule structurally similar to a cationic
polymer and contains an anionic surfactant. Its anionic surfactant was
structurally semi-stable so that it released onto scalp when it absorbs moisture.
CONCLUSION: Coacervate releases sulphate bonding into the matrix when it is
exposed to water. Thus, the scalp stimulation would be expected.
PMID- 27503110
TI - Use of metabolomics for the identification and validation of clinical biomarkers
for preterm birth: Preterm SAMBA.
AB - BACKGROUND: Spontaneous preterm birth is a complex syndrome with multiple
pathways interactions determining its occurrence, including genetic,
immunological, physiologic, biochemical and environmental factors. Despite great
worldwide efforts in preterm birth prevention, there are no recent effective
therapeutic strategies able to decrease spontaneous preterm birth rates or their
consequent neonatal morbidity/mortality. The Preterm SAMBA study will associate
metabolomics technologies to identify clinical and metabolite predictors for
preterm birth. These innovative and unbiased techniques might be a strategic key
to advance spontaneous preterm birth prediction. METHODS/DESIGN: Preterm SAMBA
study consists of a discovery phase to identify biophysical and untargeted
metabolomics from blood and hair samples associated with preterm birth, plus a
validation phase to evaluate the performance of the predictive modelling. The
first phase, a case-control study, will randomly select 100 women who had a
spontaneous preterm birth (before 37 weeks) and 100 women who had term birth in
the Cork Ireland and Auckland New Zealand cohorts within the SCOPE study, an
international consortium aimed to identify potential metabolomic predictors using
biophysical data and blood samples collected at 20 weeks of gestation. The
validation phase will recruit 1150 Brazilian pregnant women from five participant
centres and will collect blood and hair samples at 20 weeks of gestation to
evaluate the performance of the algorithm model (sensitivity, specificity,
predictive values and likelihood ratios) in predicting spontaneous preterm birth
(before 34 weeks, with a secondary analysis of delivery before 37 weeks).
DISCUSSION: The Preterm SAMBA study intends to step forward on preterm birth
prediction using metabolomics techniques, and accurate protocols for sample
collection among multi-ethnic populations. The use of metabolomics in medical
science research is innovative and promises to provide solutions for disorders
with multiple complex underlying determinants such as spontaneous preterm birth.
PMID- 27503112
TI - Feasibility of a walking virtual reality system for rehabilitation: objective and
subjective parameters.
AB - BACKGROUND: Even though virtual reality (VR) is increasingly used in
rehabilitation, the implementation of walking navigation in VR still poses a
technological challenge for current motion tracking systems. Different metaphors
simulate locomotion without involving real gait kinematics, which can affect
presence, orientation, spatial memory and cognition, and even performance. All
these factors can dissuade their use in rehabilitation. We hypothesize that a
marker-based head tracking solution would allow walking in VR with high sense of
presence and without causing sickness. The objectives of this study were to
determine the accuracy, the jitter, and the lag of the tracking system and its
elicited sickness and presence in comparison of a CAVE system. METHODS: The
accuracy and the jitter around the working area at three different heights and
the lag of the head tracking system were analyzed. In addition, 47 healthy
subjects completed a search task that involved navigation in the walking VR
system and in the CAVE system. Navigation was enabled by natural locomotion in
the walking VR system and through a specific device in the CAVE system. An HMD
was used as display in the walking VR system. After interacting with each system,
subjects rated their sickness in a seven-point scale and their presence in the
Slater-Usoh-Steed Questionnaire and a modified version of the Presence
Questionnaire. RESULTS: Better performance was registered at higher heights,
where accuracy was less than 0.6 cm and the jitter was about 6 mm. The lag of the
system was 120 ms. Participants reported that both systems caused similar low
levels of sickness (about 2.4 over 7). However, ratings showed that the walking
VR system elicited higher sense of presence than the CAVE system in both the
Slater-Usoh-Steed Questionnaire (17.6 +/- 0.3 vs 14.6 +/- 0.6 over 21,
respectively) and the modified Presence Questionnaire (107.4 +/- 2.0 vs 93.5 +/-
3.2 over 147, respectively). CONCLUSIONS: The marker-based solution provided
accurate, robust, and fast head tracking to allow navigation in the VR system by
walking without causing relevant sickness and promoting higher sense of presence
than CAVE systems, thus enabling natural walking in full-scale environments,
which can enhance the ecological validity of VR-based rehabilitation
applications.
PMID- 27503113
TI - Canthin-4-ones as Novel Antibacterial Agents.
AB - Based on the chemotype of canthin-4-one alkaloids with moderate antimicrobial
activity, a collection of variously substituted canthin-4-ones and desaza analogs
were synthesized. Key steps in the syntheses were regioselective halogenations of
(desaza) canthin-4-one, followed by Pd-catalyzed cross-coupling reactions. The in
vitro screening for antimicrobial activity revealed that two 5-substituted
canthin-4-ones (3-pyridyl, 2-bromophenyl) exhibit significant activity against
Streptococcus entericus, coupled with high selectivity and the lack of
cytotoxicity against mammalian cells. The intact canthin-4-one ring system was
demonstrated to be essential for antibacterial activity.
PMID- 27503114
TI - Simultaneous CT angiography and whole-body CT is an effective imaging approach
before multiorgan retrieval.
AB - PURPOSE: To assess the role of whole-body computed tomography (CT) for
determining morphological suitability before multiorgan retrieval (MOR) in brain
dead patients. MATERIALS AND METHODS: Fifty-one clinically brain dead patients
(21 women, 30 men; mean age 61 year+/-15) were included in this prospective,
single center study. All patients had CT angiography of the brain and whole-body
CT examination. CT images were evaluated for the presence of morphological
abnormalities of lungs, liver and other abdominal organs and presence of vascular
anatomical variants. The results of CT examinations were compared to
intraoperative findings observed during organ harvesting and/or the results of
histopathological analysis of biopsy specimens. The impact of whole-body CT
examination on the harvesting process was evaluated. RESULTS: Ninety-five percent
of vascular anatomical variants that were found intraoperatively were depicted on
CT. CT density measurements predicted surgical finding of steatosis in 80% of
patients. Whole-body CT changed the MOR strategy in 21/51 patients (41%)
including 3 MOR cancellations and 8 grafts refusals, whereas organ harvesting was
continued in 10 patients after histopathological analysis was performed.
CONCLUSION: Selection of potential graft donors using whole-body CT is reliable
and improves graft selection during MOR.
PMID- 27503115
TI - Unenhanced respiratory-navigated NATIVE(r) TrueFISP magnetic resonance
angiography in the evaluation of renal arteries: Comparison with contrast
enhanced magnetic resonance angiography.
AB - PURPOSE: To compare unenhanced three-dimensional (3D) NATIVE(r) true fast imaging
with steady-state precession (TrueFISP) magnetic resonance (MR) angiography with
the more conventional MR angiography technique obtained after intravenous
administration of a gadolinium chelate in the evaluation of renal arteries and
their branches in patients with suspected renal artery stenosis. MATERIALS AND
METHODS: A total of 39 patients (25 men, 14 women) with a mean age of 51.4+/
17.5years (SD) (range: 10-82years) were included in the study. All patients with
suspected renal artery stenosis underwent unenhanced 3D NATIVE(r) TrueFISP MR
angiography and contrast-enhanced MR angiography. The two MR angiography methods
were compared by two independent readers for image quality using a four-point
scale, diagnostic performance and grading of renal artery stenosis on a total of
78 renal arteries. RESULTS: For both readers image quality of unenhanced 3D
NATIVE(r) TrueFISP MR angiography (3.12 to 3.63) was greater than that of
contrast-enhanced MR angiography (1.94 to 2.71) for renal artery ostium-trunk and
the left renal artery segmental branches. The sensitivity of 3D NATIVE(r)
TrueFISP MR angiography for the diagnosis of renal artery stenosis was 100% for
both readers for the right renal artery and 66% and 80% for the left renal artery
for reader 1 and reader 2, respectively. Agreement between 3D NATIVE(r) TrueFISP
MR angiography and CE-MR angiography was 95% (74/78) for reader 1 and 92% (72/78)
for reader 2. CONCLUSION: Unenhanced NATIVE(r) TrueFISP magnetic resonance
angiography can play an additional role in the evaluation of renal arteries in
patients with hypertension, especially in subjects at risk of nephrogenic
systemic fibrosis.
PMID- 27503116
TI - Image fusion-guided portal vein puncture during transjugular intrahepatic
portosystemic shunt placement.
AB - PURPOSE: The purpose of this study was to assess the feasibility and utility of
image fusion (Easy-TIPS) obtained from pre-procedure CT angiography and per
procedure real-time fluoroscopy for portal vein puncture during transjugular
intrahepatic portosystemic shunt (TIPS) placement. MATERIALS AND METHODS:
Eighteen patients (15 men, 3 women) with a mean age of 63 years (range: 48-81
years; median age, 65 years) were included in the study. All patients underwent
TIPS placement by two groups of radiologists (one group with radiologists of an
experience<3 years and one with an experience>=3 years) using fusion imaging
obtained from three-dimensional computed tomography angiography of the portal
vein and real-time fluoroscopic images of the portal vein. Image fusion was used
to guide the portal vein puncture during TIPS placement. At the end of the
procedure, the interventional radiologists evaluated the utility of fusion
imaging for portal vein puncture during TIPS placement. Mismatch between three
dimensional computed tomography angiography and real-time fluoroscopic images of
the portal vein on image fusion was quantitatively analyzed. Posttreatment CT
time, number of the puncture attempts, total radiation exposure and radiation
from the retrograde portography were also recorded. RESULTS: Image fusion was
considered useful for portal vein puncture in 13/18 TIPS procedures (72%). The
mean posttreatment time to obtain fusion images was 16.4minutes. 3D volume
rendered CT angiography images was strictly superimposed on direct portography in
10/18 procedures (56%). The mismatch mean value was 0.69cm in height and 0.28cm
laterally. A mean number of 4.6 portal vein puncture attempts was made. Eight
patients required less than three attempts. The mean radiation dose from
retrograde portography was 421.2dGy.cm2, corresponding to a mean additional
exposure of 19%. CONCLUSION: Fusion imaging resulting from image fusion from pre
procedural CT angiography is feasible, safe and makes portal puncture easier
during TIPS placement.
PMID- 27503117
TI - Croceicoccus pelagius sp. nov. and Croceicoccus mobilis sp. nov., isolated from
marine environments.
AB - Strain Ery9T, isolated from surface seawater of the Atlantic Ocean, and strain
Ery22T, isolated from deep-sea sediment of the Indian Ocean, were subjected to a
taxonomic study using a polyphasic approach. Cells of the two strains were Gram
stain-negative, aerobic and rod-shaped. They produced yellow pigments and lacked
bacteriochlorophyll a. On the basis of 16S rRNA gene sequence analysis, strain
Ery9T was closely related to Croceicoccus naphthovorans PQ-2T (with 16S rRNA gene
sequence similarity of 97.7 %), and strain Ery22T was closely related to
Croceicoccusmarinus E4A9T (98.3 %). The 16S rRNA gene sequence similarity between
strain Ery9T and strain Ery22T was 96.6 %. Phylogenetic analyses revealed that
strains Ery9T and Ery22T fell within the cluster of the genus Croceicoccus and
represented two independent lineages. The average nucleotide identity (ANI)
values and the genome-to-genome distances between strains Ery9T and Ery22T and
the type strains of species of the genus Croceicoccus with validly published
names were 73.7-78.4 % and 20.1-22.3 %, respectively. The major respiratory
quinone of the two isolates was ubiquinone-10 (Q-10). The DNA G+C contents of
strains Ery9T and Ery22T were 62.8 and 62.5 mol%, respectively. Differential
phylogenetic distinctiveness and chemotaxonomic differences, together with
phenotypic properties, revealed that strains Ery9T and Ery22T could be
differentiated from their closely related species. Therefore, it is concluded
that strains Ery9T and Ery22T represent two novel species of the genus
Croceicoccus, for which the names Croceicoccus pelagius sp. nov. (type strain
Ery9T=CGMCC 1.15358T=DSM 101479T) and Croceicoccus mobilis sp. nov. (type strain
Ery22T=CGMCC 1.15360T=DSM 101481T), are proposed.
PMID- 27503118
TI - ARN: analysis and prediction by adipogenic professional database.
AB - Adipogenesis is the process of cell differentiation by which mesenchymal stem
cells become adipocytes. Extensive research is ongoing to identify genes, their
protein products, and microRNAs that correlate with fat cell development. The
existing databases have focused on certain types of regulatory factors and
interactions. However, there is no relationship between the results of the
experimental studies on adipogenesis and these databases because of the lack of
an information center. This information fragmentation hampers the identification
of key regulatory genes and pathways. Thus, it is necessary to provide an
information center that is quickly and easily accessible to researchers in this
field. We selected and integrated data from eight external databases based on the
results of text-mining, and constructed a publicly available database and web
interface (URL: http://210.27.80.93/arn/ ), which contained 30873 records related
to adipogenic differentiation. Then, we designed an online analysis tool to
analyze the experimental data or form a scientific hypothesis about adipogenesis
through Swanson's literature-based discovery process. Furthermore, we calculated
the "Impact Factor" ("IF") value that reflects the importance of each node by
counting the numbers of relation records, expression records, and prediction
records for each node. This platform can support ongoing adipogenesis research
and contribute to the discovery of key regulatory genes and pathways.
PMID- 27503120
TI - Study and interest of cellular load in respiratory samples for the optimization
of molecular virological diagnosis in clinical practice.
AB - BACKGROUND: Respiratory viral diagnosis of upper respiratory tract infections has
largely developed through multiplex molecular techniques. Although the
sensitivity of different types of upper respiratory tract samples seems to be
correlated to the number of sampled cells, this link remains largely unexplored.
METHODS: Our study included 800 upper respiratory tract specimens of which 400
negative and 400 positive for viral detection in multiplex PCR. All samples were
selected and matched for age in these 2 groups. For the positive group, samples
were selected for the detected viral species. RESULTS: Among the factors
influencing the cellularity were the type of sample (p < 0.0001); patient age (p
< 0.001); viral positive or negative nature of the sample (p = 0.002); and, for
the positive samples, the number of viral targets detected (0.004 < p < 0.049)
and viral species. CONCLUSION: The cellular load of upper respiratory samples is
multifactorial and occurs for many in the sensitivity of molecular detection.
However it was not possible to determine a minimum cellularity threshold allowing
molecular viral detection. The differences according to the type of virus remain
to be studied on a larger scale.
PMID- 27503119
TI - 2D versus 3D fluoroscopy-based navigation in posterior pelvic fixation: review of
the literature on current technology.
AB - PURPOSE: Percutaneous sacroiliac (SI) fixation of unstable posterior pelvic ring
injuries is a widely accepted procedure. The complex sacral anatomy with narrow
osseous corridors for SI screw placement makes this procedure technically
challenging. Techniques are constantly evolving as a result of better
understanding of the posterior pelvic anatomy. Recently developed tools include
fluoroscopy-based computer-assisted navigation, which can be two-dimensional (2D)
or three-dimensional (3D). Our goal is to determine the relevant technical
considerations and clinical outcomes associated with these modalities by
reviewing the published research. We hypothesize that 3D fluoroscopy-based
navigation is safer and superior to its 2D predecessor with respect to lower
radiation dose and more accurate SI screw placement. METHODS: We searched four
medical databases to identify English-language studies of 2D and 3D fluoroscopy
based navigation from January 1990 through August 2015. We included articles
reporting imaging techniques and outcomes of closed posterior pelvic ring
fixation with percutaneous SI screw fixation. Injuries included in the study were
sacral fractures (52 patients), sacroiliac fractures (88 patients), lateral
compression fractures (20 patients), and anteroposterior compression type pelvic
fractures (8 patients). We excluded articles on open reduction of posterior
pelvic ring injuries and solely anatomic studies. We then reviewed these studies
for technical considerations and outcomes associated with these technologies.
RESULTS: Six studies were included in our analysis. Results of these studies
indicate that 3D fluoroscopy-based navigation is associated with a lower
radiation dose and lower rate of screw malpositioning compared with 2D
fluoroscopy-based systems. CONCLUSIONS: It may be advantageous to combine modern
imaging modalities such as 3D fluoroscopy with computer-assisted navigation for
percutaneous screw fixation in the posterior pelvis.
PMID- 27503121
TI - Temporal and Spatial Evolution of Raised Intraspinal Pressure after Traumatic
Spinal Cord Injury.
AB - Traumatic spinal cord injury (SCI) often leads to permanent neurological
impairment. Currently, the only clinically effective intervention for patients
with acute SCI is surgical decompression by removal of impinging bone fragments
within 24 h after injury. Recent clinical studies suggest that elevated
intraparenchymal spinal pressure (ISP) limits functional recovery following SCI.
Here, we report on the temporal and spatial patterns of elevated ISP following a
moderate rodent contusion SCI. Compared with physiological ISP in the intact cord
(2.7 +/- 0.5 mm Hg), pressures increase threefold 30 min following injury (8.9 +/
1.1 mm Hg, p < 0.001) and remain elevated for up to 7 days (4.3 +/- 0.8 mm Hg).
Measurements of rostrocaudal ISP distribution reveal peak pressures in the injury
center and in segments rostral to the injury during the acute phase(<= 24 h).
During the subacute phase(>= 72 h), peak ISP decreases while a 7.5 mm long
segment of moderately elevated ISP remains, centered on the initial contusion
site. Interestingly, the contribution of the dural and pial compartments toward
increased ISP changes with time after injury: Dural and pial linings contribute
almost equally to increased ISP during the acute phase, whereas the dural lining
is primarily responsible for elevated ISP during the subacute phase (78.9%). Our
findings suggest that a rat contusion SCI model in combination with novel micro
catheters allows for direct measurement of ISP after SCI. Similarly to traumatic
brain injury, raised tissue pressure is likely to have detrimental effects on
spontaneous recovery following SCI.
PMID- 27503122
TI - Environmental chemicals impact dog semen quality in vitro and may be associated
with a temporal decline in sperm motility and increased cryptorchidism.
AB - Adverse temporal trends in human semen quality and cryptorchidism in infants have
been associated with exposure to environmental chemicals (ECs) during
development. Here we report that a population of breeding dogs exhibit a 26 year
(1988-2014) decline in sperm quality and a concurrent increased incidence of
cryptorchidism in male offspring (1995-2014). A decline in the number of males
born relative to the number of females was also observed. ECs, including
diethylhexyl phthalate (DEHP) and polychlorinated biphenyl 153 (PCB153), were
detected in adult dog testes and commercial dog foods at concentrations reported
to perturb reproductive function in other species. Testicular concentrations of
DEHP and PCB153 perturbed sperm viability, motility and DNA integrity in vitro
but did not affect LH stimulated testosterone secretion from adult testis
explants. The direct effects of chemicals on sperm may therefore contribute to
the decline in canine semen quality that parallels that reported in the human.
PMID- 27503123
TI - c-Cbl-mediated ubiquitination of IRF3 negatively regulates IFN-beta production
and cellular antiviral response.
AB - Induction of type I interferon is a fundamental cellular response to viral
infection. Interferon regulatory factor 3 (IRF3) plays an essential role in Toll
like receptor (TLR) and retinoic acid-inducible gene I (RIG-I) mediated induction
of type I interferon and host antiviral responses. However, posttranslational
regulation of IRF3 remains to be fully understood. In this study, we identified
E3 ubiquitin ligase Casitas B-lineage lymphoma (c-Cbl) as a negative regulator
for IRF3 protein stability and IFN-beta signal pathway. Knockdown of c-Cbl
expression by small interfering RNA enhanced virus-induced IFN-beta production as
well as cellular antiviral response, whereas overexpression of c-Cbl inhibited
virus-induced IFN-beta signaling. Coimmunoprecipitation experiments demonstrated
that c-Cbl interacted with IRF3 via TKB domain of c-Cbl and IRF association
domain of IRF3, promoting K48-linked polyubiquitination and proteasomal
degradation of IRF3. Therefore, our findings suggest that c-Cbl negatively
regulates IFN-beta signaling and cellular antiviral response by promoting IRF3
ubiquitination and degradation, providing a new mechanism for control of type I
interferon induction.
PMID- 27503125
TI - Merocyanine 540 adsorbed on polyethylenimine-functionalized graphene oxide
nanocomposites as a turn-on fluorescent sensor for bovine serum albumin.
AB - Graphene oxide (GO)-based fluorescence sensors are attractive and versatile tools
for various sensing applications. Herein, we report the photophysical properties
of merocyanine 540 (MC540) in an aqueous dispersion including graphene oxide (GO)
and GO chemically functionalized with branched polyethylenimine (PEI), and the
application of a novel designed MC540/PEI-GO system for BSA (bovine serum
albumin) detection. Initially, the negatively charged GO surface was modified
using PEI to form high positively charged PEI-GO nanocomposites via the amine
groups of PEI. Later, to form MC540/PEI-GO system, MC540 molecules were assembled
on PEI-GO nanocomposites having an attractive surface for negatively charged
functional materials. The interaction of MC540 molecules with PEI-GO
nanocomposites in aqueous dispersion led to a change in the photophysical
properties of the dye. The variations in the photophysical properties of MC540
were spectroscopically characterized and explained. It was determined that the
interaction of MC540 with GO sheets and PEI-GO nanocomposites strongly quenched
the fluorescence of the dye. However, the quenching effect of the PEI-GO
nanocomposites on the fluorescence of MC540 was specifically prevented by the
addition of BSA, in which the fluorescence of MC540 was nearly recovered. By
using the PEI-GO nanocomposites-based fluorescence platform, BSA has been
detected with a LOD (limit of detection) of 7.45 nM, which is one of the best
applications among BSA sensors to date. The designed sensor system was easily
applied for the detection of BSA in commonly used biological media and clinical
injectable fluids. Consequently, we suggest a simple, fast, sensitive and
selective BSA sensor designed by assembling MC540 molecules on PEI-GO
nanocomposites.
PMID- 27503124
TI - The combination of herbal medicine Weng-li-tong with Tolterodine may be better
than Tolterodine alone in the treatment of overactive bladder in women: a
randomized placebo-controlled prospective trial.
AB - BACKGROUND: To assess the efficacy and safety of the herbal medicine, Weng-li
tong (WLT) as monotherapy or combined with tolterodine in women with overactive
bladder (OAB). METHODS: A prospective, randomized, single-blind multi-center
trial was performed which included 182 OAB patients treated with either placebo
(n = 26), WLT (n = 52), tolterodine (n = 52) or WLT plus tolterodine (n = 52).
The overactive bladder symptom score (OABSS) and micturition behavior were
measured to evaluate treatment efficacy. RESULTS: In total, 146 patients [placebo
(n = 23), WLT (n = 39), tolterodine (n = 41) and WLT plus tolterodine (n = 43)]
completed 8 weeks of treatment. Compared to those treated with placebo, patients
in three intervention groups showed significant improvements in the OABSS,
voiding frequency, average voided volume and urgency incontinence. WLT had a
slower onset than tolterodine or combination therapy in reducing urgency
incontinence. Compared with tolterodine, WLT had a weaker effect in improving
OABSS (P = 0.022) and daily voiding frequency (P = 0.034). The combination
therapy had better efficacy than WLT or tolterodine alone in improving the OABSS,
voiding frequency and voided volume. No significant differences in the changes in
quality of life scores were observed among the three intervention groups.
Residual urine increased significantly in tolterodine group (P = 0.004), but not
in combination group. WLT resulted in fewer adverse effects than tolterodine such
as dry mouth (P = 0.002), weak stream (P = 0.002) and less residual urine (P <
0.001). CONCLUSIONS: WLT could improve OAB symptoms in women, while it had slower
onset and weaker efficacy but fewer adverse effects than tolterodine. The
combination of WLT and tolterodine was more efficacious than tolterodine alone in
improving OAB symptoms. TRIAL REGISTRATION: Chinese Clinical Trial Registry [
ChiCTR-IPR-14005626 ]. Date of registration: 7 December 2014.
PMID- 27503126
TI - Rehabilitation of atrophic anophthalmic cavity with orthostatic ocular
prosthesis: A clinical report.
AB - The absence of the eyeball can generate psychosocial and facial harmony changes,
such as atrophy of the muscles around it. In these cases, the use of an
orthostatic prosthesis with expanding function fosters distension of the tissues
for subsequent rehabilitation. This technique consists of making individual
ocular prostheses with gradual enlargement of size. The aim of this following
clinical report was to describe the technique used in the standing prosthetic
rehabilitation of a patient, 73 years old, who underwent enucleation of the right
eye as a result of glaucoma. Clinical and laboratory procedures were performed
such as impression, adjusting curvature of the sclera, centering the pupil area
and processing in heat-cured acrylic resin three prostheses made according to the
expansion of the anophthalmic cavity. At the end of treatment, there was a
considerable increase of the cavity, allowing for volume replacement similar to
that existing in the patient's contralateral orbit, thus generating a
satisfactory facial harmony.
PMID- 27503127
TI - Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal
epithelium and induces gut microbial shifts in murine model.
AB - Gut microbiota dysbiosis are associated with a wide range of human diseases,
including inflammatory bowel diseases. The physiopathology of these diseases has
multifactorial aetiology in which environmental factors, particularly pollution
could play a crucial role. Among the different pollutants listed, Polycyclic
Aromatic Hydrocarbons (PAHs) are subject to increased monitoring due to their
wide distribution and high toxicity on Humans. Here, we used 16S rRNA gene
sequencing to investigate the impact of benzo[a]pyrene (BaP, most toxic PAH) oral
exposure on the faecal and intestinal mucosa-associated bacteria in C57BL/6 mice.
Intestinal inflammation was also evaluated by histological observations. BaP oral
exposure significantly altered the composition and the abundance of the gut
microbiota and led to moderate inflammation in ileal and colonic mucosa. More
severe lesions were observed in ileal segment. Shifts in gut microbiota
associated with moderate inflammatory signs in intestinal mucosa would suggest
the establishment of a pro-inflammatory intestinal environment following BaP oral
exposure. Therefore, under conditions of genetic susceptibility and in
association with other environmental factors, exposure to this pollutant could
trigger and/or accelerate the development of inflammatory pathologies.
PMID- 27503128
TI - Familial occurrence of autoimmune liver disease with overlapping features of
primary biliary cholangitis and autoimmune hepatitis in a mother and her
daughter.
AB - We encountered two patients with overlapping features of primary biliary
cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman
presented at our hospital from a previous medical institution because of the
diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted
with liver dysfunction 4 years later. When compared, these two related patients
were found to have overlapping features of primary biliary cholangitis and
autoimmune hepatitis. Their human leukocyte antigen haplotype was
DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two
patients immediately improved following treatment with a combination of
prednisolone and ursodeoxycholic acid, in accordance with the Japanese
guidelines. It is extremely important to identify such pathological conditions as
quickly as possible, particularly with the appearance of severe liver dysfunction
due to liver cirrhosis, as observed in our case. The Japanese guidelines are
considered to be a realistic and useful clinical policy for the swift and
efficient treatment of patients with overlapping features of primary biliary
cholangitis and autoimmune hepatitis. We suggest that our two patients presented
with a genetic predisposition to autoimmune liver disease with overlapping
features of primary biliary cholangitis and autoimmune hepatitis within the same
family.
PMID- 27503129
TI - Mesalazine allergy in a boy with ulcerative colitis: clinical usefulness of
mucosal biopsy criteria.
AB - 5-Aminosalicylic acid preparations have been used as first-line drugs for
treatment of ulcerative colitis (UC). However, some patients with UC present with
exacerbation of symptoms because of allergy to mesalazine. Diagnosis of
mesalazine allergy in active UC may be challenging because its symptoms mimic
those of UC. Here we describe a 13-year-old boy with mesalazine allergy who
achieved remission when his medication was changed from mesalazine to
salazosulfapyridine. During his clinical course mesalazine was prescribed twice,
and on each occasion exacerbation of the symptoms occurred. We considered a
diagnosis of mesalazine allergy, and this was confirmed by a drug lymphocyte
stimulation test; the result for salazosulfapyridine was negative. On the basis
of criteria involving simple mucosal biopsy combined with endoscopy for
predicting patients with UC who would ultimately require surgery, we considered
that the UC in this case might be susceptible to steroid treatment, and we
therefore treated the patient with salazosulfapyridine and prednisolone. Shortly
afterwards, remission was achieved and the patient has remained in good condition
on salazosulfapyridine alone. When treating patients with mesalazine, the
possibility of allergy should always be borne in mind, especially when the
clinical course is inconsistent with the results of biopsy.
PMID- 27503130
TI - Can interprofessional practice solve the vexing question of 'What is occupational
therapy'?
PMID- 27503131
TI - There is some evidence from non-randomised trials that team interventions improve
processes and outcomes in rehabilitation and chronic care settings.
PMID- 27503132
TI - A single virtual patient education activity led to improvements in some self
reported interprofessional competencies in approximately 40% of students.
PMID- 27503134
TI - The role of periodic serum CA19-9 test in surveillance after colorectal cancer
surgery.
AB - BACKGROUND: The serum carcinoembryonic antigen (CEA) test is mainly used for
postoperative surveillance of colorectal cancer patients in Western and Japanese
guidelines, but evidence to support the use of CA19-9 is scarce. METHODS: We
analyzed the cohort data from 22 institutions of the Japanese Study Group for
Postoperative Follow-up of Colorectal Cancer. Patients who had undergone curative
surgery for primary colorectal cancer (pathological stage I-III) between 1997 and
2006 were eligible for analysis. Sensitivities of CEA and CA19-9 at the time of
recurrence and the contribution of CA19-9 to detecting recurrences were assessed.
RESULTS: A total of 17,833 patients were eligible, and the overall recurrence
rate was 18 %. The sensitivity of CA19-9 in detecting recurrence was lower than
that of CEA (29 vs. 57 %). Among patients with recurrence, recurrences were first
suspected in 96 % using standard surveillance modalities (CEA elevation, CT scan,
clinic visit, and colonoscopy), whereas recurrences were suspected because of
CA19-9 elevation in an estimated 1.3 % of patients. With regard to prognosis
after recurrences, the sensitivity of CA19-9 was lower than that of CEA in the
detection of surgically treatable recurrences (22 vs. 49 %). In terms of overall
survival after recurrences, CA19-9 and CEA had almost comparable hazard ratios
(1.66 and 1.48, respectively). CONCLUSIONS: Our data suggested that the
sensitivity of serum CA19-9 test is low, and that adding it to the current
standard surveillance strategies is not beneficial.
PMID- 27503135
TI - Erratum to: Why so many deep brain stimulation targets in Tourette's syndrome?
Toward a broadening of the definition of the syndrome.
PMID- 27503136
TI - A nickel iron diselenide-derived efficient oxygen-evolution catalyst.
AB - Efficient oxygen-evolution reaction catalysts are required for the cost-effective
generation of solar fuels. Metal selenides have been reported as promising oxygen
evolution catalysts; however, their active forms are yet to be elucidated. Here
we show that a representative selenide catalyst, nickel selenide, is entirely
converted into nickel hydroxide under oxygen-evolution conditions. This result
indicates that metal selenides are unstable during oxygen evolution, and the in
situ generated metal oxides are responsible for their activity. This knowledge
inspired us to synthesize nanostructured nickel iron diselenide, a hitherto
unknown metal selenide, and to use it as a templating precursor to a highly
active nickel iron oxide catalyst. This selenide-derived oxide catalyses oxygen
evolution with an overpotential of only 195 mV for 10 mA cm(-2). Our work
underscores the importance of identifying the active species of oxygen-evolution
catalysts, and demonstrates how such knowledge can be applied to develop better
catalysts.
PMID- 27503137
TI - Association of nerve conduction impairment and insulin resistance in children
with obesity.
AB - AIM: The objective of our study was to investigate nerve conduction in
normoglycemic obese children. METHODS: A total of 60 children with obesity (30
female and 30 male) and 30 healthy children (15 female and 15 male) were enrolled
in the study. Insulin resistance (IR) and other metabolic disturbances were
investigated and nerve conduction was measured in all participants. Obese
children were divided into groups according to the presence of IR. All results
were compared between these subgroups. RESULTS: The nerve conduction velocity
(NCV) of motor median nerves in the IR+ group was significantly higher than that
in the IR- group and lower than that in the control group. The NCV of the motor
peroneal nerve in the IR+ group was significantly lower than that in the IR-
group. The sensory nerve action potential (SNAP) of the sensory median nerve was
significantly lower in the IR+ group compared to that in the IR- group. The
sensory sural nerve's SNAP was significantly lower in the IR+ group than that in
the control group. CONCLUSION: Nerve conduction tests may help to detect early
pathologies in peripheral nerves and to decrease morbidities in obese children.
PMID- 27503139
TI - Dynamic self-representation of interdependent Chinese: The effect of bicultural
experience.
AB - The process of globalisation has increased the opportunity for Chinese
individuals to utilise influences from other cultures that differ from their own
collectivistic culture. The explorations of the impact of acculturation on
Chinese individuals' self-construals have become intriguing. Thus, we recruited
German-Chinese (N = 192) people who live in Germany and had direct bicultural
experiences, as well as Mainland-Chinese (N = 192) people who live in Mainland
China and had internalised a second culture through more indirect means of
exposure. We investigated their accessibility to both interdependent and
independent cultural frameworks using temporal self-construal priming. The
results showed that priming effects were observed in both cultural groups.
However, the self-construals of the German-Chinese participants were more
flexible than those of Mainland-Chinese under self-construal priming. Also, the
results suggested that women were easier to be influenced by direct bicultural
experiences, due to their private and collective self were different between the
two cultures. These findings provide evidence regarding the opinion that
individuals could use influences from more than one culture. More importantly,
these results suggest that the acculturation induced by direct bicultural
experiences facilitates cultural frame switching.
PMID- 27503140
TI - Beard alopecia areata: a multicentre review of 55 patients.
AB - BACKGROUND: Alopecia areata on the beard area (BAA) is a common clinical
manifestation, but there are no studies about its characteristics. OBJECTIVE: To
describe the epidemiology, comorbidities, clinical presentation, evolution,
diagnostic findings and therapeutic choices in a series of patients with BAA.
METHODS: This retrospective multicentre review included patients diagnosed with
BAA as the first and unique clinical manifestation with at least 12 months of
follow-up. Diagnosis was performed based on the typical clinical features. Extra
beard involvement was monitored in all cases. RESULTS: Overall, 55 male patients
with a mean age of 39.1 years (range 20-74) were included. Twenty-five patients
(45.5%) developed alopecia of the scalp during follow-up and more than 80% of
cases appeared in the first 12.4 months. Clinical presentation of AA on the scalp
was patchy AA (less than 5 patches) (52%), multifocal AA (28%), AA totalis (12%)
and AA universalis (8%). Multivariate analysis revealed a trend of association
between scalp involvement and family history of AA without statistical
significance. CONCLUSIONS: According to this study, BAA may progress to scalp AA
in a significant number of patients (45.5% of the patients with a follow-up
interval of at least 12 months). In the group of patients who developed scalp AA,
80% of them did it within the first 12 months, so follow-up of patients with BAA
is highly encouraged.
PMID- 27503138
TI - A combination of TERT promoter mutation and MGMT methylation status predicts
clinically relevant subgroups of newly diagnosed glioblastomas.
AB - The prognostic impact of TERT mutations has been controversial in IDH-wild
tumors, particularly in glioblastomas (GBM). The controversy may be attributable
to presence of potential confounding factors such as MGMT methylation status or
patients' treatment. This study aimed to evaluate the impact of TERT status on
patient outcome in association with various factors in a large series of adult
diffuse gliomas. We analyzed a total of 951 adult diffuse gliomas from two
cohorts (Cohort 1, n = 758; Cohort 2, n = 193) for IDH1/2, 1p/19q, and TERT
promoter status. The combined IDH/TERT classification divided Cohort 1 into four
molecular groups with distinct outcomes. The overall survival (OS) was the
shortest in IDH wild-type/TERT mutated groups, which mostly consisted of GBMs (P
< 0.0001). To investigate the association between TERT mutations and MGMT
methylation on survival of patients with GBM, samples from a combined cohort of
453 IDH-wild-type GBM cases treated with radiation and temozolomide were
analyzed. A multivariate Cox regression model revealed that the interaction
between TERT and MGMT was significant for OS (P = 0.0064). Compared with TERT
mutant-MGMT unmethylated GBMs, the hazard ratio (HR) for OS incorporating the
interaction was the lowest in the TERT mutant-MGMT methylated GBM (HR, 0.266),
followed by the TERT wild-type-MGMT methylated (HR, 0.317) and the TERT wild-type
MGMT unmethylated GBMs (HR, 0.542). Thus, patients with TERT mutant-MGMT
unmethylated GBM have the poorest prognosis. Our findings suggest that a
combination of IDH, TERT, and MGMT refines the classification of grade II-IV
diffuse gliomas.
PMID- 27503143
TI - Nondestructive Encapsulation of CdSe/CdS Quantum Dots in an Inorganic Matrix by
Pulsed Laser Deposition.
AB - We report the successful encapsulation of colloidal quantum dots in an inorganic
matrix by pulsed laser deposition. Our technique is nondestructive and thus
permits the incorporation of CdSe/CdS core/shell colloidal quantum dots in an
amorphous yttrium oxide matrix (Y2O3) under full preservation of the advantageous
optical properties of the nanocrystals. We find that controlling the kinetic
energy of the matrix precursors by means of the oxygen pressure in the deposition
chamber facilitates the survival of the encapsulated species, whose well
conserved optical properties such as emission intensity, luminescence spectrum,
fluorescence lifetime, and efficiency as single-photon emitters we document in
detail. Our method can be extended to different types of nanoemitters (e.g.,
nanorods, dots-in-rods, nanoplatelets) as well as to other matrices (oxides,
semiconductors, metals), opening up new vistas for the realization of fully
inorganic multilayered active devices based on colloidal nano-objects.
PMID- 27503141
TI - Advances in the characterization of RNA-binding proteins.
AB - From transcription, to transport, storage, and translation, RNA depends on
association with different RNA-binding proteins (RBPs). Methods based on next
generation sequencing and protein mass-spectrometry have started to unveil genome
wide interactions of RBPs but many aspects still remain out of sight. How many of
the binding sites identified in high-throughput screenings are functional? A
number of computational methods have been developed to analyze experimental data
and to obtain insights into the specificity of protein-RNA interactions. How can
theoretical models be exploited to identify RBPs? In addition to oligomeric
complexes, protein and RNA molecules can associate into granular assemblies whose
physical properties are still poorly understood. What protein features promote
granule formation and what effects do these assemblies have on cell function?
Here, we describe the newest in silico, in vitro, and in vivo advances in the
field of protein-RNA interactions. We also present the challenges that
experimental and computational approaches will have to face in future studies.
WIREs RNA 2016, 7:793-810. doi: 10.1002/wrna.1378 For further resources related
to this article, please visit the WIREs website.
PMID- 27503144
TI - Structural Stability and Deformation of Solvated Sm@C2(42)-C90 under High
Pressure.
AB - Solvated fullerenes recently have been shown to exhibit novel compression
behaviors compared with the pristine fullerenes. However, less attention has been
focused on the large cage endohedral metallofullerenes. Here, we have firstly
synthesized solvated Sm@C90 microrods by a solution drop-drying method, and then
studied the transformations under high pressure. The pressure-induced structural
evolutions of Sm@C90 molecules both undergo deformation and collapse. The band
gaps of both samples decrease with increasing pressure. The trapped Sm atom plays
a role in restraining the compression of the adjacent bonds. The solvent plays a
role in protecting Sm@C90 against collapse in the region of 12-20 GPa, decreasing
and postponing the change of band gap. Above 30 GPa, the carbon cages collapse.
Released from 45 GPa, the compressed solvated Sm@C90 forms a new ordered
amorphous carbon cluster (OACC) structure with metal atoms trapped in the units
of amorphous carbon clusters, which is different from the OACC structure formed
by compressing solvated C60 and C70. This discovery opens the door for the
creation of new carbon materials with desirable structural and physical
properties when suitable starting materials are selected.
PMID- 27503142
TI - The venom gland transcriptome of the parasitoid wasp Nasonia vitripennis
highlights the importance of novel genes in venom function.
AB - BACKGROUND: Prior to egg laying the parasitoid wasp Nasonia vitripennis
envenomates its pupal host with a complex mixture of venom peptides. This venom
induces several dramatic changes in the host, including developmental arrest,
immunosuppression, and altered metabolism. The diverse and potent bioactivity of
N. vitripennis venom provides opportunities for the development of novel acting
pharmaceuticals based on these molecules. However, currently very little is known
about the specific functions of individual venom peptides or what mechanisms
underlie the hosts response to envenomation. Many of the venom peptides also lack
bioinformatically derived annotations because no homologs can be identified in
the sequences databases. The RNA interference system of N. vitripennis provides a
method for functional characterisation of venom protein encoding genes, however
working with the current list of 79 candidates represents a daunting task. For
this reason we were interested in determining the expression levels of venom
encoding genes in the venom gland, as this information could be used to rank
candidates for further study. To do this we carried out deep transcriptome
sequencing of the venom gland and ovary tissue and used RNA-seq to rank the venom
protein encoding genes by expression level. The generation of a specific venom
gland transcriptome dataset also provides further opportunities to investigate
novel features of this specialised organ. RESULTS: RNA-seq revealed that the
highest expressed venom encoding gene in the venom gland was 'Venom protein Y'.
The highest expressed annotated gene in this tissue was serine protease
Nasvi2EG007167, which has previously been implicated in the apoptotic activity of
N. vitripennis venom. As expected the RNA-seq confirmed that venom encoding genes
are almost exclusively expressed in the venom gland relative to the neighbouring
ovary tissue. Novel genes appear to perform key roles in N. vitripennis venom
function, with over half of the 15 highest expressed venom encoding loci lacking
bioinformatic annotations. The high throughput sequencing data also provided
evidence for the existence of an additional 472 previously undescribed
transcribed regions in the N. vitripennis genome. Finally, metatranscriptomic
analysis of the venom gland transcriptome finds little evidence for the role of
Wolbachia in the venom system. CONCLUSIONS: The expression level information
provided here for the N. vitripennis venom protein encoding genes represents a
valuable dataset that can be used by the research community to rank candidates
for further functional characterisation. These candidates represent bioactive
peptides valuable in the development of new pharmaceuticals.
PMID- 27503145
TI - Extensive herpes simplex infection of the skin in an immunocompetent, previously
skin-healthy female patient.
PMID- 27503147
TI - Reflections on my association with Henry G. Kunkel.
PMID- 27503146
TI - The Kunkel legacy and hepatitis C virus infection.
AB - In commemoration of Henry Kunkel's 100th birthday, the effect of his legacy on
the investigation of hepatitis C virus is recounted. The delineation of a major
cross-idiotype (WA) among patients with essential mixed cryoglobulinemia led to
the discovery that HCV was the etiologic agent for this disease. Studies of the
cryoglobulins led to the discovery that WA RF reacted specifically with HCV-VLDL
like particles that on electronmicroscopy and binding studies appeared to be the
virion within a lipid shell. This particle mediates cell entry via LDLr and may
serve to avoid the immune response by masking the virion. In addition, the WA B
cell may be a prognostic marker for cutaneous vasculitis and B cell malignancy in
HCV-infected patients. In commemoration of Henry Kunkel's 100th birthday, this is
an account of how his legacy had a role in the investigation of hepatitis C virus
(HCV) infection. There is a bit of a historical basis for the legacy of this
great immunologist having a role in virology. He began his research career
studying hepatitis. Later he worked with HCV in his studies of mixed
cryoglobulins although he didn't know it at the time. There may also have been a
Kunkel historical basis for why he accepted me as fellow in his laboratory
considering that my credentials paled in comparison with those of the fellows and
PhD students in his laboratory. Like Henry I was drafted into the Navy following
my internship, I had had minimal research experience in medical school and only
one minor publication, and I had a passion for clinical investigation. It may
have been fortuitous that while on active duty at the Bayonne NJ Naval Base I
visited Henry Kunkel in my Navy uniform and told him I was interested in studying
SLE. I did not know at the time the dramatic role the Navy had played in his
career or that one of his major training goals was to teach MDs to use clinical
observation as a focus for delineating disease mechanisms in the laboratory. When
I started work in the laboratory on discharge from the Navy, the first thing he
told me was that it took five years to make a clinical investigator so I might as
well get a Rockefeller University PhD while working in his laboratory. I was sure
I would leave the laboratory after two years so I declined his offer. I did not
leave until six years later!
PMID- 27503148
TI - 3D Printing Variable Stiffness Foams Using Viscous Thread Instability.
AB - Additive manufacturing of cellular structures has numerous applications ranging
from fabrication of biological scaffolds and medical implants, to mechanical
weight reduction and control over mechanical properties. Various additive
manufacturing processes have been used to produce open regular cellular
structures limited only by the resolution of the printer. These efforts have
focused on printing explicitly designed cells or explicitly planning offsets
between strands. Here we describe a technique for producing cellular structures
implicitly by inducing viscous thread instability when extruding material. This
process allows us to produce complex cellular structures at a scale that is finer
than the native resolution of the printer. We demonstrate tunable effective
elastic modulus and density that span two orders of magnitude. Fine grained
cellular structures allow for fabrication of foams for use in a wide range of
fields ranging from bioengineering, to robotics to food printing.
PMID- 27503150
TI - Phosphonium pillar[5]arenes as a new class of efficient biofilm inhibitors:
importance of charge cooperativity and the pillar platform.
AB - Biofilm formation, which frequently occurs in microbial infections and often
reduces the efficacy of antibiotics, also perturbs many industrial and domestic
processes. We found that a new class of water soluble pillar[5]arenes bearing
phosphonium moieties (1, 2) and their respective ammonium analogues (3, 4)
inhibit biofilm formation with IC50 values in the range of 0.67-1.66 MUM. These
compounds have no antimicrobial activity, do not damage red blood cell membranes,
and do not affect mammalian cell viability in culture. Comparison of the
antibiofilm activities of the phosphonium-decorated pillar[5]arene derivatives 1
and 2 with their respective ammonium counterparts 3 and 4 and their monomers 5
and 6, demonstrate that while positive charges, charge cooperativity and the
pillararene platform are essential for the observed antibiofilm activity the
nature of the charges is not.
PMID- 27503149
TI - A sex difference in oxidative stress and behavioral suppression induced by
ethanol withdrawal in rats.
AB - Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy
drinking, and provokes oxidative brain damage. Here, we investigated whether the
cerebellum and hippocampus of female rats are less affected by prooxidant EW than
male rats due to the antioxidant effect of 17beta-estradiol (E2). Female and male
rats received a four-week ethanol diet and three-week withdrawal per cycle for
two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin
E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus
(water-maze)-related behaviors, oxidative markers (O2(-), malondialdehyde,
protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial
enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were
subjected to ethanol-exposure and withdrawal for two cycles to assess the effect
of a CcO inhibitor on E2's protection for mitochondrial respiration and cell
viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative
markers in cerebellum and hippocampus than male rats, and E2 treatment decreased
the oxidative markers. Compared to male counterparts, ethanol-withdrawn female
rats showed better Rotarod but poorer water-maze performance, accompanied by more
severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or
antioxidant treatment improved Rotarod but not water-maze performance. In the
presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial
respiration and cell viability from EW. These data suggest that antioxidant E2
contributes to smaller oxidative stress in ethanol-withdrawn female than male
rats. They also suggest that EW-induced severe mitochondrial damage in
hippocampus may blunt E2's antioxidant protection for hippocampus-related
behavior.
PMID- 27503151
TI - What's in a name? Pancreatic pseudocysts, walled-off necrosis, and pancreatic
fluid collections.
PMID- 27503152
TI - Utility of endoscopic ultrasound in the diagnosis and management of
esophagogastric varices.
AB - Endoscopic ultrasound (EUS) has significantly improved our understanding of the
complex vascular structural changes in patients with portal hypertension. At
present, EUS is a useful diagnostic tool for the evaluation of esophagogastric
varices (EGVs) and guidance of endoscopic therapy. Several studies have employed
this new technique for the diagnosis and management of esophageal and gastric
varices, respectively. In the present review, we have summarized the current
status of EUS for the diagnosis and management of EGVs and clarified the clinical
feasibility of this procedure. New indications for EUS can be developed in the
future after adequate validation.
PMID- 27503153
TI - Efforts to improve the diagnostic accuracy of endoscopic ultrasound-guided fine
needle aspiration for pancreatic tumors.
AB - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to
obtain a definitive diagnosis of pancreatic tumors. Good results have been
reported for its diagnostic accuracy, with high sensitivity and specificity of
around 90%; however, technological developments and adaptations to improve it
still further are currently underway. The endosonographic technique can be
improved when several tips and tricks useful to overcome challenges of EUS-FNA
are known. This review provides various techniques and equipment for improvement
in the diagnostic accuracy in EUS-FNA.
PMID- 27503155
TI - In vivo cytological observation of liver and spleen by using high-resolution
microendoscopy system under endoscopic ultrasound guidance: A preliminary study
using a swine model.
AB - Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is useful to obtain
specimens from lesions underlying deep parts of the liver and spleen. However,
the development of novel ancillary techniques must be explored to reduce the
number of needle passes and potential adverse effects during this procedure. We
conducted an animal study using a swine to demonstrate technical feasibility of
in vivo cytological observation of liver and spleen using the high-resolution
microendoscopy (HRME) system under EUS guidance. We successfully performed the
study. No significant acute adverse events occurred during the procedure. The
HRME system could obtain clear images representing cytology-level morphology of
spleen and liver. Hence, it is found out that in vivo cytological observation of
liver and spleen using the HRME system under EUS guidance is technically
feasible.
PMID- 27503154
TI - Endobronchial ultrasound elastography.
AB - Elastographic techniques have recently become available as advanced diagnostic
tools for tissue characterization. Strain elastography is a real-time technique
used with transcutaneous ultrasound (US) and endoscopic US. Convincing evidence
is available demonstrating a significant value of strain elastography for the
discrimination of benign and malignant lymph nodes (LNs). This paper reviews
preliminary data demonstrating the feasibility of performing real-time
elastography during endobronchial US (EBUS) and a potential application of this
technique for selection of LNs for EBUS-guided transbronchial needle aspiration
in patients with lung cancer and extrathoracic malignancies.
PMID- 27503156
TI - Usefulness of lymphoid granulomatous inflammation culture obtained by
endobronchial ultrasound-guided transbronchial needle aspiration in a fungal
endemic area.
AB - BACKGROUND AND OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle
aspiration (EBUS-TBNA) is the procedure of choice for the evaluation of
mediastinal/hilar lymph node enlargements. Granulomatous inflammation of the
mediastinal/hilar lymph nodes is often identified on routine histology. In
addition, mediastinal lymphadenopathy may be present with undiagnosed infection.
We sought to determine the usefulness of routine cultures and histology for
infectious etiologies in a fungal endemic area when granulomatous inflammation is
identified. MATERIALS AND METHODS: We identified 56 of 210 patients with
granulomatous inflammation on EBUS-TBNA biopsies from October 2012 through
October 2014. An onsite cytologist evaluated all biopsies and an additional TBNA
pass for microbiologic stains and cultures were obtained in those with
granulomatous inflammation. RESULTS: Of the 56 patients with granulomatous
inflammation, 20 patients had caseating (necrotizing) granulomas while
noncaseating (nonnecrotizing) granulomas were detected in 36 of the remainder
patients. In patients with caseating granulomas, fungal elements were identified
in 6 of 20 (30%) patients (histoplasma; N = 5, blastomyces; N = 1) on Grocott
methenamine silver (GMS) stain. Lymph node cultures identified 3 of 20 (20%)
patients as being positive for Mycobacterium tuberculosis (N = 1), Histoplasma
capsulatum (N = 1), and Blastomyces dermatitidis (N = 1). Among patients with
noncaseating granulomas, only 2 out of 36 (5%) were positive for fungal elements
on GMS stain, identified as Histoplasma, although the lymph node cultures
remained negative. CONCLUSION: The incidence of granulomatous inflammation of
mediastinal lymph nodes was 26.6% in our series. Of these patients, noncaseating
granulomas were more common (64% vs. 36%). Infectious organisms, fungal or acid
fast bacilli (AFB), on either staining or lymph node culture were rarely
identified in noncaseating granulomas, 5% and none, respectively. Caseating
granulomas were more commonly associated with positive lymph node fungal stain
and culture, 35% and 15%, respectively. In a fungal endemic area, lymph node
staining and culture can be considered in cases with caseating granulomatous
inflammation, if known at the time of biopsy.
PMID- 27503157
TI - Endoscopic ultrasound characteristics of pancreatic lymphoepithelial cysts: A
case series from a large referral center.
AB - BACKGROUND AND OBJECTIVES: Lymphoepithelial cysts (LECs) of the pancreas are
benign lesions that can mimic cystic neoplasms on imaging. Endoscopic ultrasound
(EUS) features have not been well described. We aimed to describe the clinical
and EUS characteristics of LECs and the present outcomes of management at a high
volume referral center. MATERIALS AND METHODS: We identified patients who
underwent EUS and were found to have LECs based on fine-needle aspiration (FNA)
cytology or surgical pathology from existing databases. EUS features, imaging
characteristics, and pathology results were described. RESULTS: Sixteen patients
were found to have 17 LECs. The mean size was 33 mm +/- 15 mm. Locations within
the pancreas included 10 lesions in the tail, 3 in the body, 1 in the uncinate
process; the remaining 3 were exophytic. Six lesions were anechoic, 6 were
hypoechoic, and 5 had mixed echogenicity. Nine lesions had mixed solid/cystic
components, 7 were purely cystic, and 1 was solid. Cyst fluid was thick or
viscous in six cases and thin in three. Eleven patients had diagnostic
cytopathology. Six patients ultimately underwent surgery due to symptoms,
nondiagnostic FNA, or other clinical concerns for malignancy. CONCLUSIONS:
Pancreatic LECs have variable morphology and echogenicity on EUS, but the
appearance of a cyst with variable solid and cystic components combined with the
appearance of thick, turbid, and viscous aspirate should raise suspicion for an
LEC. The majority of patients with LECs at our center avoided surgery for LECs on
the basis of diagnostic EUS-FNA.
PMID- 27503158
TI - Exploration under the dome: Esophageal ultrasound with the ultrasound
bronchoscope is indispensible.
AB - BACKGROUND: Effective use of the convex curvilinear ultrasound bronchoscope in
the esophagus (EUS-B) for fine needle aspiration biopsy of mediastinal structures
is now well described. In contrast, there is little to no reporting, depending on
the site of EUS-B for access to sub-diaphragmatic structures. Our practice has
been accessing sub-diaphragmatic sites for years. This review documents our
experience with EUS-B to biopsy liver, left adrenal glands, and coeliac lymph
nodes. METHODS: After Institutional Review Board's approval, all endosonographic
procedures performed by interventional pulmonary between July 2013 and June 2015
were reviewed. Those including biopsy of sub-diaphragmatic sites were then
selected for analysis. RESULTS: Over the study interval, 45 sub-diaphragmatic
biopsy procedures (25 left adrenal glands, 7 liver, and 13 celiac node) were
performed with EUS-B. In all cases, cellular adequacy was present, and samples
were large enough for immunohistochemistry and any relevant ancillary studies.
Metastatic malignancy was documented in 58% of cases, 16% of cases contained
benign diagnostic findings, and in 27% of cases, normal organ tissue was
documented. There were no complications. CONCLUSIONS: Operators comfortable with
the endobronchial ultrasound scope in both the airway and the esophagus can
actively seek and successfully perform biopsy of sub-diaphragmatic abnormalities
when present and can thereby add to the diagnostic value of the procedure.
PMID- 27503159
TI - Repeat endoscopic ultrasound fine needle aspiration after a first negative
procedure is useful in pancreatic lesions.
AB - BACKGROUND AND OBJECTIVES: There is no consensus about the ideal method for
diagnosis in patients who have already undergone endoscopic ultrasound fine
needle aspiration (EUS-FNA), and the inconclusive material is often obtained. The
aim was to evaluate the diagnostic yield of the second EUS-FNA of pancreatic
lesions. MATERIALS AND METHODS: A retrospective analysis of prospectively
collected data of patients with EUS-FNA of pancreatic lesions is performed. All
patients who underwent more than one EUS-FNA for the evaluation of suspected
pancreatic cancer over a 7-year period were included in the analysis. RESULTS: A
total of 296 EUS-FNAs of the pancreas were performed in 257 patients. The
diagnostic yield with the first EUS-FNA was 78.6% (202/257). Thirty-nine (13.3%)
FNAs were repeated in 34 patients; 17 (50%) patients were women. The mean +/-
standard deviation (SD) age was 58.8 +/- 16.1 years. The location of the lesions
in the pancreatic gland, from which the second biopsies were taken, was head of
the pancreas, n = 28 (82.4%), body of the pancreas, n = 3 (8.8%), and tail, n = 3
(8.8%). The mean +/- SD of the size of the lesion was 36.3 +/- 14.6 mm. The
second EUS-FNA was more likely to be positive for diagnosis in patients with an
"atypical" histological result in the first EUS-FNA (odds ratio [OR]: 4.04; 95%
confidence interval [CI]: 0.9-18.3), in contrast to patients with a first EUS-FNA
reported as "normal" (OR: 0.21; 95% CI: 0.06-0.71). Overall, the diagnostic yield
of the second EUS-FNA was 58.8% (20/34) with an increase to 86.3% overall
(222/257). CONCLUSION: Repeat EUS-FNA in pancreatic lesions is necessary in
patients with a negative first EUS-FNA because it improves the diagnostic yield.
PMID- 27503160
TI - Endoscopic ultrasound-guided puncture suture device versus metal clip for gastric
defect closure after endoscopic full-thickness resection: A randomized,
comparative, porcine study.
AB - OBJECTIVE: The secure closure of the wall defect is a critical stage of
endoscopic full-thickness resection (EFTR). The aim of this study was to compare
the closure of post-EFTR defects using an endoscopic ultrasound-guided puncture
suture device (PSD) with the metal clip (MC) technique in a randomized,
comparative, porcine study. METHODS: We performed a randomized comparative
survival study that included 18 pigs. The circular EFTR defects with a diameter
of approximately 20 mm were closed with either a PSD or MC. Serum levels of
interleukin-6 (IL-6) were determined preoperatively and on a postoperative day
(POD) 1, 3, and 7. Three animals from each group were sacrificed at the end of
the 7 th , 14 th , and 30 th POD. Tissue samples retrieved from the closure sites
were examined macroscopically and microscopically. RESULTS: Resection and closure
were performed in 18 pigs (100%) without major perioperative complications. The
mean closure time was significantly longer in the MC group than in the PSD group
(25.00 +/- 3.16 min vs. 1.56 +/- 0.39 min; P < 0.05). Preoperative and POD 7
serum levels of IL-6 did not differ between the two groups. However, on POD 1,
the IL-6 levels were observed to be significantly greater in the MC group than in
the PSD group (P < 0.005). No significant differences between the PSD and MC
groups were observed at necropsy. CONCLUSION: In this in vivo porcine model, PSD
is a feasible device that achieves post-EFTR defect closure with a much shorter
closure time and with less immunological responses than the MC technique.
PMID- 27503161
TI - Opium-related sphincter of Oddi dysfunction causing double duct sign.
AB - Double duct sign where there is a simultaneous dilatation of both the common bile
duct (CBD) and pancreatic duct is usually associated with sinister causes like
malignancies of pancreatic head or ampulla. Occasionally, benign causes like
chronic pancreatitis or sphincter of Oddi dysfunction (SOD) may cause double duct
sign. Chronic opium abuse is a rare cause of the double duct sign, and endoscopic
ultrasound (EUS) findings of this rare entity have been occasionally reported. We
report about a 54-year-old male with a history of chronic alcohol and opioid
abuse evaluated for episodes of abdominal pain and found to have opioid-related
SOD and improved with biliary sphincterotomy. EUS was done to rule out malignancy
and revealed hypoechoic prominence around terminal CBD suggestive of
hypertrophied muscle.
PMID- 27503162
TI - Endobronchial ultrasound for the detection of chronic pulmonary artery thrombus.
AB - Endobronchial ultrasound (EBUS) has been shown to be able to successfully
identify acute/subacute pulmonary thromboembolism (PE). Most reported cases have
required confirmation by computerized tomography (CT) angiography. This report
demonstrates a case where CT angiography was not conclusive and the EBUS was
useful in clarifying the chronic process inside the pulmonary artery compatible
with clinical diagnosis of chronic pulmonary artery thrombosis.
PMID- 27503163
TI - Biliary intraductal papillary-mucinous neoplasm in the left hepatic lobe
diagnosed by endoscopic ultrasonography: Report of a case.
PMID- 27503164
TI - Endoscopic ultrasound-guided internalization of a pancreaticocutaneous fistula
without need for percutaneous manipulation.
PMID- 27503165
TI - EUS-FNA diagnosis of a rare case of esophageal teratoma.
PMID- 27503166
TI - The relationship between living alone and depressive symptoms among older gay
men: the moderating role of sense of belonging with gay friends.
AB - BACKGROUND: Living alone is a risk factor for depressive symptoms among older
adults, although it is unclear if it is a risk factor for older gay men. A sense
of belonging to the gay community is protective and might compensate for living
alone. This research investigated whether a sense of belonging with gay friends
weakened the relationship between living alone and depressive symptoms among
older gay men. METHODS: A community sample of 160 Australian gay men aged 65-92
years completed the Center for Epidemiologic Studies Depression Scale and two
visual analogue scales assessing a sense of belonging with gay friends. RESULTS:
Results supported the moderation model, with increasing levels of belonging with
gay friends weakening the relationship between living alone and depressive
symptoms. CONCLUSION: Results imply that enhancing a sense of belonging with gay
friends among older gay men who live alone is likely to be a protective factor in
relation to depressive symptoms.
PMID- 27503167
TI - Development of myotendinous-like junctions that anchor cardiac valves requires
fibromodulin and lumican.
AB - BACKGROUND: There are many patients that exhibit connective tissue related
cardiac malformations but do not have mutations in collagen genes. The Small
Leucine Rich Proteoglycans (SLRP) fibromodulin (FMOD) and lumican (LUM) bind
collagen and regulate fibril assembly in other biological contexts. RESULTS: FMOD
deficient mice and double deficient FMOD; LUM mice exhibited anomalies in regions
where cardiac valve tissue interdigitates with adjacent muscle for support.
Ectopic connective and/or myocardial tissue(s) was associated with the more
severe cardiac valve anomalies in FMOD; LUM deficient mice. At postnatal day 0
(P0) there was an increase in the mesenchymal cell number in the regions where
valve cusps anchor in FMOD; LUM deficient mice compared to WT. The cardiac valve
anomalies correlated with the highest levels of FMOD expression in the heart and
also where myotendinous junctions (MTJ) components biglycan, collagen type I
alpha 1, and collagen type VI, are also localized. CONCLUSIONS: The postnatal
assembly of the collagen-rich ECM in regions where cardiac valves anchor, that we
have designated 'myotendinous-like junctions' (MTLJ) requires the SLRPs FMOD and
LUM. Moreover, FMOD and LUM may facilitate mesenchymal cell differentiation in
late stages of cardiac valve development. Developmental Dynamics 245:1029-1042,
2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27503168
TI - Screening anti-allergic components of Astragali Radix using LAD2 cell membrane
chromatography coupled online with UHPLC-ESI-MS/MS method.
AB - Huangqi (Astragali Radix), a traditional Chinese herb, is widely used in clinical
therapy in China. In addition, an anti-allergic effect of constituents in Huangqi
has been reported in the scientific literature. In the present study, cell
membrane chromatography coupled online with UHPLC-ESI-MS/MS method was developed
to screen, analyze and identify the anti-allergic components of Huangqi. The
Laboratory of Allergic Disease 2 (LAD2) cell was used to establish cell membrane
chromatography, which was combined with UHPLC-ESI-MS/MS. The coupled system was
then used to screen anti-allergic components from Huangqi. Effects of active
components were verified by histamine release assay. A component retained on the
LAD2 cell membrane chromatography was identified as formononetin. Bioactivity of
formononetin was investigated by histamine release assay in LAD2 cells, and it
was found that formononetin could inhibit histamine release in a dose-dependent
manner from 1 to 100 MUm. The LAD2 cell membrane chromatography online with UHPLC
ESI-MS/MS method is an effective technique for screening the anti-allergic
components of Huangqi.
PMID- 27503169
TI - A 'suicide' CRISPR-Cas9 system to promote gene deletion and restoration by
electroporation in Cryptococcus neoformans.
AB - Loss-of-function mutagenesis is an important tool used to characterize gene
functions, and the CRISPR-Cas9 system is a powerful method for performing
targeted mutagenesis in organisms that present low recombination frequencies,
such as the serotype D strains of Cryptococcus neoformans. However, when the
CRISPR-Cas9 system persists in the host cells, off-target effects and Cas9
cytotoxicity may occur, which might block subsequent genetic manipulation. Here,
we report a method of spontaneously eliminating the CRISPR-Cas9 system without
impairing its robust editing function. We successfully expressed single guide RNA
under the driver of an endogenous U6 promoter and the human codon-optimized Cas9
endonuclease with an ACT1 promoter. This system can effectively generate an indel
mutation and efficiently perform targeted gene disruption via homology-directed
repair by electroporation in yeast. We then demonstrated the spontaneous
elimination of the system via a cis arrangement of the CRISPR-Cas9 expression
cassettes to the recombination construct. After a system-mediated double
crossover, the CRISPR-Cas9 cassettes were cleaved and degraded, which was
validated by Southern blotting. This 'suicide' CRISPR-Cas9 system enables the
validation of gene functions by subsequent complementation and has the potential
to minimize off-target effects. Thus, this technique has the potential for use in
functional genomics studies of C. neoformans.
PMID- 27503171
TI - Considerations concerning the definition of sarcopenia: response to comments.
PMID- 27503170
TI - Associations of dietary calcium intake with metabolic syndrome and bone mineral
density among the Korean population: KNHANES 2008-2011.
AB - : Excessive amount of calcium intake increased risk for metabolic syndrome in
men. However, modest amount decreased the risk of metabolic syndrome and
osteoporosis in postmenopausal women. Modest amount of calcium also increased
bone mineral density (BMD) in both men and postmenopausal women. INTRODUCTION:
The present study aimed to evaluate the associations of dietary calcium intake
with metabolic syndrome and bone mineral density (BMD) in Korean men and women,
especially postmenopausal women. METHODS: The study was performed using data from
the Korean National Health and Nutrition Examination Survey (2008-2011) and
included 14,705 participants (5953 men, 4258 premenopausal women, and 4494
postmenopausal women). Clinical and other objective characteristics, presence of
metabolic syndrome, and the BMD of the femur neck and lumbar spine were evaluated
according to dietary calcium intake. RESULTS: There was a higher tendency for
metabolic syndrome in men with a dietary calcium intake of >1200 mg/day than with
<=400 mg of calcium intake; >400 and <=800 mg of calcium intake was helpful for
postmenopausal women to decrease risk for metabolic syndrome. Overall, the group
with calcium intake >400 and <=800 mg daily had significantly increased BMD in
both femoral neck and lumbar spine from both men and postmenopausal women. From
both femoral neck and lumbar spine, the prevalence of osteoporosis in
postmenopausal women significantly decreased in the group whose calcium intake
was >400 and <=800 mg daily. CONCLUSION: Excessive dietary calcium may increase
the prevalence of metabolic syndrome in men. For postmenopausal women, calcium
intake does not increase the risk of metabolic syndrome, but modest amount
decreases the risk. It may increase the BMD in men and postmenopausal women, and
also reduce the prevalence of both osteoporosis and metabolic syndrome in
postmenopausal women.
PMID- 27503172
TI - Considerations concerning the definition of sarcopenia: comments.
PMID- 27503173
TI - Health-related quality of life in older people with osteoporotic vertebral
fractures: clinically important vs. statistically significant.
PMID- 27503174
TI - Health-related quality of life in older people with osteoporotic vertebral
fractures: response to comments by Sani et al.
PMID- 27503175
TI - Thalassemia-associated osteoporosis: a systematic review on treatment and brief
overview of the disease.
AB - Thalassemia-associated osteoporosis constitutes a major complication in patients
with thalassemia. This review presents the existing studies on the treatment of
thalassemia-associated osteoporosis and discusses the management of this
debilitating complication. A brief presentation of the disease characteristics
and pathogenetic mechanisms is also provided. The life expectancy of patients
with thalassemia has increased markedly in recent years resulting in the aging of
the population and the emergence of new comorbidities. The majority of patients
with thalassemia have low bone mineral density and experience lifelong fracture
rates as high as 71 %. The pathogenesis of thalassemia-associated osteoporosis
(TAO) is multifactorial with anemia and iron overload playing crucial role in its
development. Data concerning the prevention and treatment of TAO are extremely
limited. We performed a literature research in Pubmed and Scopus to identify
interventional studies evaluating the effects of various agents on TAO. Seventeen
studies were retrieved. We present the results of these studies as well as a
brief overview of TAO including presentation, pathogenesis, and management. Most
of the studies identified are of poor quality, are not randomized controlled, and
include small number of participants. There are no data concerning effects on
fracture rates. Bisphosphonates are the most widely studied agents and among them
zoledronic acid is the most well studied. Hormone replacement treatment (HRT)
shows beneficial but small effects. Denosumab and strontium ranelate have each
been evaluated in only a single study, while there are no data about the effects
of anabolic agents. Given the increased life expectancy and the increase in
fracture rates with age, more data about the management of TAO are warranted.
Moreover, due to the need for lifelong management starting at young age, careful
treatment plans which may include sequential treatment may often be required.
However, currently, there are no relevant data available.
PMID- 27503176
TI - The Association of Vitamin D With Estimated Glomerular Filtration Rate and
Albuminuria: 5th Korean National Health and Nutritional Examination Survey 2011
2012.
AB - OBJECTIVES: The kidney plays a key role in the metabolism of vitamin D. However,
the relationship between GFR and 25(OH)D is not well understood. Moreover, few
studies have investigated the effect of albuminuria, a known mediator of kidney
function, on vitamin D levels. Our aim was to investigate the associations among
estimated GFR (eGFR), albumin-creatinine ratio (ACR), and 25(OH)D. METHODS: We
investigated the relationship of 25-hydroxyvitamin D (25[OH]D) with eGFR and
albuminuria in 11,336 adults who participated in the 5th Korea National Health
and Nutrition Examination Survey (KNHANES) 2011-2012. The eGFR, ACR, and serum
25(OH)D were measured in participants who met the detailed inclusion criteria.
RESULTS: We found that after adjusting for covariates and log-ACR values, the
mean (95% CI) eGFR decreased significantly with increasing 25(OH)D levels (Q1:
93.4 [92.7-94.0]; Q2: 91.9 [91.2-92.5]; Q3: 90.9 [90.3-91.6]; and Q4: 90.2 [89.5
90.8] mL/min/1.73m2; P < .001). However, the mean 25(OH)D value was highest at
eGFR 61-90 mL/min per 1.73 m2 and decreased significantly with decreasing eGFR
levels (>90: 17.3 [17.1-17.5]; 61-90: 17.6 [17.4-17.8]; 46-60: 17.1 [16.2-18.0];
31-45: 16.2 [14.2-18.2]; <=30: 13.8 [17.0-10.7] ng/mL; P = .008). After adjusting
for covariates and log-eGFR, the mean ACR decreased significantly with increasing
25(OH)D quartiles (Q1: 22.0 [18.1-25.9]; Q2: 20.4 [16.6-24.2]; Q3: 16.3 [12.5
20.0]; Q4: 15.0 [11.2-18.8] MUg/mg; P = .043). CONCLUSIONS: The mean eGFR values
were negatively associated with 25(OH)D levels independently of ACR. However, the
mean 25(OH)D values were decreased significantly with decreasing eGFR levels in
moderate and severe chronic kidney disease stages. Also, the mean ACR values were
negatively associated with 25(OH)D levels independently of eGFR in an Korean
adult population.
PMID- 27503177
TI - Japanese secular trends in birthweight and the prevalence of low birthweight
infants during the last three decades: A population-based study.
AB - Since low birthweight has been correlated with both neonatal and long-term
health, we performed this epidemiological study to evaluate the Japanese secular
trends in mean birthweight and the prevalence of preterm/term low birthweight
infants during the last three decades. We used population-based birth certificate
data from January 1979 to December 2010. Time trends were analysed using a linear
regression model. During the study period, we observed a significant decrease in
the mean birthweight for singleton live births (3,152 +/- 436 g in 1979 and 3,018
+/- 421 g in 2010 p < 0.001) and an increase in the prevalence of preterm/term
low birthweight infants. A 96.3% increase in the proportion of term low
birthweight infants was observed during the study period (2.7% in 1979 and 5.3%
in 2010). In addition, an increased proportion of preterm/low birthweight infants
born to younger women was observed (<35 years vs. >=35 years). These trends may
be related to changing patterns in Japanese women's nutritional status and the
relatively strict recommended limit on weight gain during pregnancy.
Understanding the long-term trends for singleton births may allow us to identify
the associated risk factors and reduce the future socioeconomic burden that is
associated with low birthweight infants.
PMID- 27503178
TI - Effect of autoimmunity risk loci on the honeymoon phase in type 1 diabetes.
AB - OBJECTIVE: To analyze the correlation between duration and depth of honeymoon
phase in patients with type 1 diabetes (T1DM) and autoimmunity risk loci.
METHODS: From a database of 567 individuals with clinical data, we selected 210
patients for whom we had dense genotyping results of single-nucleotide
polymorphisms (SNPs) from our previous genome-wide association studies (GWAS) or
targeted genotyping data. Using PLINK software, we analyzed the association
between time spent in honeymoon phase as our quantitative trait, and 24 known
autoimmunity predisposing SNPs. RESULTS: We found one allele on chromosome 5,
rs4613763 mapping to a Prostaglandin Receptor EP4 (PTGER4) to reach statistical
significance (P = .0067), in determining a larger proportion of T1DM patients
with a detectable honeymoon phase. This polymorphism determines risk for
inflammatory bowel disease (IBD) but not T1DM. CONCLUSION: By showing the role of
PTGER4 in autoimmune diseases and its effect on inflammatory responses via its
interaction with NF-kB, we hypothesize that PTGER4 modulates honeymoon phase in
patients with T1DM without influencing the risk of developing T1DM. We
hypothesize that this quantitative trait locus promotes inflammatory suppression
of beta cells without directly promoting beta-cell destruction. Understanding
SNPs that effect function can provide insight in to pathogenesis of T1DM and the
mechanism of the honeymoon phase. Because this is a hypothesis-generating study,
it needs to be replicated in an additional larger cohort.
PMID- 27503179
TI - Nano-Bio Interactions: Guiding the Development of Nanoparticle Therapeutics,
Diagnostics, and Imaging Agents.
PMID- 27503180
TI - Newly Approved Agents for the Treatment and Prevention of Pediatric Migraine.
AB - Treatment of pediatric migraine remains an unmet medical need. There continues to
be a paucity of pediatric randomized controlled trials for the treatment of
migraine, both in the acute and preventive settings. Pediatric studies are often
complicated by high placebo-response rates and much of our current practice is
based on adult trials. This lack of significant pediatric studies results in a
wide variation in migraine management both amongst clinicians and between
institutions, and evidence-based treatments are not always administered. In this
article, we aim to briefly review newly approved abortive and preventive agents
for migraine in the pediatric age group. Over-the-counter anti-inflammatory
medications, including ibuprofen, naproxen sodium, aspirin, and acetaminophen are
reasonable first-line options for abortive therapy. In addition, studies have
shown triptans, or migraine-specific agents, to be safe and effective in children
and adolescents and several formulations have been approved for the pediatric
population, including rizatriptan, almotriptan, zolmitriptan nasal spray, and
naproxen sodium/sumatriptan in combination.
PMID- 27503182
TI - Electronic Consultations in Nephrology: Pilot Implementation and Evaluation.
PMID- 27503181
TI - Brivaracetam: A Review in Partial-Onset (Focal) Seizures in Patients with
Epilepsy.
AB - Brivaracetam (Briviact((r)); BRIVLERATM) is a high affinity synaptic vesicle
protein 2A (SV2A) ligand available orally (as a tablet or solution) or
intravenously (as a bolus or infusion) in various countries worldwide, including
the USA, Canada and those of the EU. It is approved as adjunctive therapy for the
treatment of partial-onset seizures (POS) in adults (aged >=18 years) [USA, EU
and Canada] and adolescents (aged 16 to <18 years) [USA and EU] with epilepsy. In
multinational, phase III studies in adults and adolescents (aged >=16 years),
oral brivaracetam as adjunctive therapy to other antiepileptic drugs (AEDs) was
generally associated with significant median percent reductions over placebo in
seizure frequency and significant improvements in the proportion of patients
achieving a >=50 % reduction in seizure frequency compared with placebo. These
benefits appeared to be sustained during up to 96 months' therapy in follow-up
studies. Whether administered orally or intravenously, adjunctive brivaracetam
was generally well tolerated in clinical studies, with the majority of treatment
emergent adverse events (TEAEs) being mild or moderate in intensity. In the
absence of head-to-head studies, definitive conclusions on the comparative
efficacy and tolerability of brivaracetam versus newer AEDs are not yet possible.
In the meantime, brivaracetam extends the options currently available for the
treatment of POS in patients aged >=16 years with epilepsy.
PMID- 27503183
TI - Febuxostat in Hyperuricemic Patients With Advanced CKD.
PMID- 27503184
TI - The influence of tibial resection on the PCL in PCL-retaining total knee
arthroplasty: A clinical and cadaveric study.
AB - BACKGROUND: The influence of tibial resection on the joint gap and on stability
against posterior laxity in posterior cruciate ligament-retaining total knee
arthroplasty (CR-TKA) remains unclear. In addition, there are no detailed reports
regarding how much of the tibial attachment of the posterior cruciate ligament
(PCL) is preserved during tibial resection. Our goals were to evaluate the
influence of tibial resection on the intraoperative joint gap and on
postoperative anteroposterior stability in a clinical population, and to assess
the preserved area of the tibial PCL attachment using cadaveric knees. METHODS:
In 20 consecutive patients, the joint gaps before and after tibial resection at
90 degrees flexion and full extension were analyzed during CR-TKA, and
anteroposterior stability was evaluated postoperatively. In 11 cadaveric knees,
tibial resection with a thickness of 8, 10, 12, or 14 mm and a posterior slope of
3, 4, 5, 6, or 7 degrees was simulated using computed tomography images, and the
percentage of the preserved area of the attachment was calculated. RESULTS: The
flexion gaps before and after tibial resection were 18.1 +/- 1.9 mm and 18.4 +/-
2.2 mm, respectively, with no statistically significant difference (p = 0.08).
Similarly, the extension gap did not increase significantly before and after
tibial resection (20.8 +/- 2.5 mm and 21.0 +/- 2.6 mm; p = 0.45). All knees
maintained anteroposterior stability at the follow-up period (32.0 +/- 1.9
months). The posterior slope of the tibial resection was 5.9 +/- 1.4 degrees ,
and the thickness of the lateral tibial resection was 10.4 +/- 1.1 mm. The
cutoffs to preserve more than 50% of the attachment were 10-mm thickness and 5
degrees slope. CONCLUSIONS: Our results showed that tibial resection did not
influence the intraoperative joint gap or postoperative anteroposterior
stability. However, our analysis demonstrated that increased amounts of tibial
resection led to considerable damage to the attachment.
PMID- 27503185
TI - Leukocyte concentration and composition in platelet-rich plasma (PRP) influences
the growth factor and protease concentrations.
AB - BACKGROUND: Platelet-rich plasma (PRP) therapy has become an increasingly popular
treatment for orthopaedics and sports-related injuries, and various clinically
available PRP preparation methods exist. However, the differences in PRP quality
among numerous preparation methods remain unclear. Specifically, the benefit of
including leukocytes in the PRP product remains controversial, and few studies
have been conducted to evaluate the effects of the interaction between platelets
and leukocytes on the growth factor concentrations. The aim of the present study
was to compare the biological characteristics of PRPs focusing on the leukocyte
concentration and composition. METHODS: Leucocyte rich (LR)-PRP, leucocyte poor
(LP)-PRP, and pure-PRP were prepared from the peripheral blood of 6 healthy male
volunteers (mean age: 31.3 years). The concentrations of platelets, leukocytes,
erythrocytes, growth factors (transforming growth factor-beta 1: TGF-beta1;
fibroblast growth factor-basic: FGF-b; platelet-derived growth factor-BB: PDGF
BB; vascular endothelial growth factor: VEGF) and matrix metalloproteinase-9 (MMP
9) from each of the PRP samples were measured. Considering the interaction
between platelets and leukocytes, correlations between platelets/leukocytes and
growth factors/MMP-9 were analyzed using partial correlation coefficients.
RESULTS: The platelet concentration did not differ among the three PRP
preparation methods. Conversely, the leukocyte concentration was dramatically
different: 14.9 +/- 4.5 (10(3)/MUl) in LR-PRP, 2.4 +/- 1.3 (10(3)/MUl) in LP-PRP,
0.2 +/- 0.2 (10(3)/MUl) in pure-PRP. The platelet concentration positively
correlated with all growth factors. On the other hand, the leukocyte
concentration positively correlated with PDGF-BB and the VEGF concentration,
while it negatively correlated with FGF-b. Regarding catabolic factors, the MMP-9
concentration strongly correlated with the leukocyte concentration, while there
was no correlation between the platelet and MMP-9 concentrations. CONCLUSIONS:
These findings demonstrate that leukocytes strongly influence the quality of
PRPs. Therefore, modifying the PRP preparation method according to the pathology
is essential to achieve better clinical results with PRP therapy.
PMID- 27503186
TI - Paraarticular osteochondroma of a lumbar facet joint presenting with
radiculopathy.
PMID- 27503187
TI - Evaluation of three-dimensional scapular kinematics and shoulder function in
patients with short malunion of clavicle fractures.
AB - BACKGROUND: The presence of short malunion of clavicle fractures could result in
alterations in static scapular position and dynamic scapular motion.
Nevertheless, no report has ever addressed the kinematic changes of the scapula
in patients with short malunion of clavicular fractures. The goal of this study
was to compare the changes of shoulder function, and the consequent scapular
kinematic changes between the fractured side and the sound side of the shoulder
in non-surgically treated patients. METHODS: Fourteen patients with a short
malunion (>10 mm) of midshaft clavicular fracture following conservative
treatment were recruited. Outcome analysis included standard clinical follow-up,
plain radiography, Shoulder Pain and Disability Index (SPADI) score, shoulder
range of motion (ROM), shoulder muscle strength and scapular resting position.
The 3-dimensional scapular motion during arm movement in the scapular plane was
recorded using an electromagnetic tracking device. The kinematic changes between
the fractured side and sound side were analyzed. RESULTS: The mean shortening
length of the clavicle was 12.9 +/- 2.8 mm. The fractured sides showed a
significantly higher SPADI score and limited ROM in both shoulder flexion and
abduction. Significantly weaker shoulder external rotators (1.1 kg, p = 0.017)
and lower trapezius (0.7 kg, p = 0.041) were found in the fractured sides when
compared with the sound side. The fractured side exhibited significantly more
forward shoulder (3.9 mm, p = 0.034) and slightly more anteriorly tilted scapula
(5.8 degrees , p = 0.094) in static scapular position. Scapular kinematics showed
that the fractured side trended toward greater scapular internal rotation and
smaller posterior tilt during arm elevation and lowering phases, especially after
the arm rising above horizontal level. CONCLUSIONS: This study showed that
significant changes in scapular kinematics and shoulder function were found after
short malunion of clavicle fractures. Recognition and evaluation of the changes
could lead to a comprehensive framework regarding the treatment of shortened
clavicle fractures.
PMID- 27503188
TI - Chemically-doped graphene with improved surface plasmon characteristics: an
optical near-field study.
AB - One of the most fascinating and important merits of graphene plasmonics is their
tunability over a wide range. While chemical doping has proven to be a facile and
effective way to create graphene plasmons, most of the previous studies focused
on the macroscopic behaviors of the plasmons in chemically-doped graphene and
little was known about their nanoscale responses and related mechanisms. Here, to
the best of our knowledge, we present the first experimental near-field optical
study on chemically-doped graphene with improved surface plasmon characteristics.
By using a scattering-type scanning near-field optical microscope (s-SNOM), we
managed to show that the graphene plasmons can be tuned and improved using a
facile chemical doping method. Specifically, the plasmon interference patterns
near the edge of the monolayer graphene were substantially enhanced via nitric
acid (HNO3) exposure. The plasmon-related characteristics can be deduced by
analyzing such plasmonic fringes, which exhibited a longer plasmon wavelength and
reduced plasmon damping rate. In addition, the local carrier density and
therefore the Fermi energy level (EF) of graphene can be obtained from the
plasmonic nano-imaging, which indicated that the enhanced plasmon oscillation
originated from the injection of free holes into graphene by HNO3. These findings
were further corroborated by theoretical calculations using density functional
theory (DFT). We believe that our findings provide a clear nanoscale picture on
improving graphene plasmonics by chemical doping, which will be helpful for
optimizing graphene plasmonics and for elucidating the mechanisms of two
dimensional light confinement by atomically thick materials.
PMID- 27503189
TI - Richness of ectoparasitic flies (Diptera: Streblidae) of bats (Chiroptera)-a
systematic review and meta-analysis of studies in Brazil.
AB - The family Streblidae consists of obligate hematophagous ectoparasites of bats.
The richness of Streblidae may be affected by environmental and host-related
variables, collection methods, and sampling effort. The purposes of this study
were to list the Streblidae species recorded in Brazil, verify their distribution
in the Brazilian biomes and states, and pinpoint the parameters that favored the
greatest richness. Through queries in online databases and libraries, 86
publications were found containing records of 83 species in 24 genera. The state
with the largest number of publications was Sao Paulo and Federal District
presented the highest richness of Streblidae. The largest number of records of
Streblidae species was in Cerrado biome. The meta-analyses utilizing 26 Brazilian
inventories showed that the richness of Streblidae was positively correlated with
the number of flies and richness and abundance of Phyllostomidae. We hope that
the results of this study will contribute to a better understanding of the
distribution of research on Streblidae in Brazil and confirming the specificity
between Streblidae and Phyllostomidae.
PMID- 27503190
TI - A Survey of Graduates of Combined Emergency Medicine-Pediatrics Residency
Programs: An Update.
AB - BACKGROUND: In 1998, emergency medicine-pediatrics (EM-PEDS) graduates were no
longer eligible for the pediatric emergency medicine (PEM) sub-board
certification examination. There is a paucity of guidance regarding the various
training options for medical students who are interested in PEM. OBJECTIVES: We
sought to to determine attitudes and personal satisfaction of graduates from EM
PEDS combined training programs. METHODS: We surveyed 71 graduates from three EM
PEDS residences in the United States. RESULTS: All respondents consider their
combined training to be an asset when seeking a job, 92% find it to be an asset
to their career, and 88% think it provided added flexibility to job searches. The
most commonly reported shortcoming was their ineligibility for the PEM sub-board
certification. The lack of this designation was perceived to be a detriment to
securing academic positions in dedicated children's hospitals. When surveyed
regarding which training offers the better skill set for the practice of PEM, 90%
(44/49) stated combined EM-PEDS training. When asked which training track gives
them the better professional advancement in PEM, 52% (23/44) chose combined EM
PEDS residency, 27% (12/44) chose a pediatrics residency followed by a PEM
fellowship, and 25% (11/44) chose an EM residency then a PEM fellowship. No EM
PEDS respondents considered PEM fellowship training after the completion of the
dual training program. CONCLUSION: EM-PEDS graduates found combined training to
be an asset in their career. They felt that it provided flexibility in job
searches, and that it was ideal training for the skill set required for the
practice of PEM. EM-PEDS graduates' practices varied, including mixed settings,
free-standing children's hospitals, and community emergency departments.
PMID- 27503192
TI - Design, syntheses, characterization, and cytotoxicity studies of novel
heterobinuclear oxindolimine copper(II)-platinum(II) complexes.
AB - Herein, the design and syntheses of two new mononuclear oxindolimine-copper(II)
(1 and 2) and corresponding heterobinuclear oxindolimine Cu(II)Pt(II) complexes
(3 and 4), are described. All the isolated complexes were characterized by
spectroscopic techniques (UV/Vis, IR, EPR), in addition to elemental analysis and
mass spectrometry. Cyclic voltammetry (CV) measurements showed that in all cases,
one-electron quasi-reversible waves were observed, and ascribed to the formation
of corresponding copper(I) complexes. Additionally, waves related to oxindolimine
ligand reduction was verified, and confirmed using analogous oxindolimine-Zn(II)
complexes. The Pt(IV/II) reduction, and corresponding oxidation, for complexes 3
and 4 occurred at very close values to those observed for cisplatin. By
complementary fluorescence studies, it was shown that glutathione (GSH) cannot
reduce any of these complexes, under the experimental conditions (room
temperature, phosphate buffer 50mM, pH7.4), using an excess of 20-fold [GSH]. All
these complexes showed characteristic EPR spectral profile, with parameters
values g||>g? suggesting an axially distorted environment around the copper(II)
center. Interactions with calf thymus-DNA, monitored by circular dichroism (CD),
indicated different effects modulated by the ligands. Finally, the cytotoxicity
of each complex was tested toward different tumor cells, in comparison to
cisplatin, and low values of IC50 in the range 0.6 to 4.0MUM were obtained, after
24 or 48h incubation at 37 degrees C. The obtained results indicate that such
complexes can be promising alternative antitumor agents.
PMID- 27503191
TI - Identifying common barriers and facilitators to linkage and retention in chronic
disease care in western Kenya.
AB - BACKGROUND: Sub-Saharan Africa is increasingly being challenged in providing care
and treatment for chronic diseases, both communicable and non-communicable. In
order to address the challenges of linkage to and retention in chronic disease
management, there is the need to understand the factors that can influence
engagement in care. We conducted a qualitative study to identify barriers and
facilitators to linkage and retention in chronic care for HIV, tuberculosis (TB)
and Hypertension (HTN) as part of the Academic Model Providing Access to
Healthcare (AMPATH) program in western Kenya. METHODS: In-depth interviews and
focus group discussions were conducted July 2012-August 2013. Study participants
were purposively sampled from three AMPATH clinics and included patients within
the AMPATH program receiving HIV, TB, and HTN care, as well as caregivers of
children with HIV, community leaders, and healthcare providers. A set of
interview guides were developed to explore perceived barriers and facilitators to
chronic disease management, particularly related to linkage to and retention in
HIV, TB and HTN care. Data were coded and various themes were identified. We
organized the concepts and themes generated using the Andersen-Newman Framework
of Health Services Utilization. RESULTS: A total of 235 participants including
110 individuals living with HIV (n = 50), TB (n = 39), or HTN (n = 21); 24
caregivers; 10 community leaders; and 62 healthcare providers participated.
Barriers and facilitators were categorized as predisposing characteristics,
enabling resources and need factors. Many of the facilitators and barriers
reported in this study were consistently reported across disease categories
including personal drive, patient-provider relationships and the need for social
and peer support. CONCLUSIONS: Our findings provide insight into the individual
as well as broader structural factors that can deter or encourage linkage and
retention that are relevant across communicable and non-communicable chronic
diseases. The findings of the present study suggest that interventions should
consider the logistical aspects of accessing care in addition to predisposing and
need factors that may affect an individuals' decision to seek out and remain in
appropriate care.
PMID- 27503193
TI - Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG
PET/CT in anal canal cancer.
AB - PURPOSE: The aim of this study was to confirm the prognostic value of metabolic
tumour volume (MTV) at the primary site on initial work-up FDG PET/CT in patients
with squamous cell carcinoma (SCC) of the anal canal. METHODS: Patients with a
recent diagnosis of SCC of the anal canal without metastases undergoing PET/CT
for initial work-up and treated with (chemo)radiotherapy were retrospectively
reviewed. Computer-aided MTV and SUVmax were determined. Survival rates were
estimated using the Kaplan-Meier method. Cox regression analysis was used to
evaluate prognostic variables of progression-free survival and overall survival
(OS). RESULTS: The study group comprised 75 patients who had an initial work-up
PET/CT. Five patients (6.7 %) had stage I disease, 22 (29.3 %) stage II disease,
20 (26.7 %) stage IIIA disease, and 28 (37.3 %) stage IIIB disease. Median follow
up was 51 months (range 10 - 117 months). Global 4-year OS was 82.7 %, ranging
from 100 % in patients with stage I disease to 75 % in patients with stage IIIB
disease. MTV at the primary site was significantly and independently correlated
with OS (p < 0.05), as patients with MTV less than 7 cm3 had a better prognosis.
SUVmax was not correlated with survival parameters. Metabolic involvement of the
inguinal lymph nodes was also correlated with a poor outcome in the univariate
analysis (p < 0.05). CONCLUSION: MTV at the primary site is a prognostic
biomarker in anal canal cancer. Hypermetabolic inguinal lymph nodes also appear
to be correlated with survival.
PMID- 27503194
TI - Researchers' choice of the number and range of levels in experiments affects the
resultant variance-accounted-for effect size.
AB - In psychology, the reporting of variance-accounted-for effect size indices has
been recommended and widely accepted through the movement away from null
hypothesis significance testing. However, most researchers have paid insufficient
attention to the fact that effect sizes depend on the choice of the number of
levels and their ranges in experiments. Moreover, the functional form of how and
how much this choice affects the resultant effect size has not thus far been
studied. We show that the relationship between the population effect size and
number and range of levels is given as an explicit function under reasonable
assumptions. Counterintuitively, it is found that researchers may affect the
resultant effect size to be either double or half simply by suitably choosing the
number of levels and their ranges. Through a simulation study, we confirm that
this relation also applies to sample effect size indices in much the same way.
Therefore, the variance-accounted-for effect size would be substantially affected
by the basic research design such as the number of levels. Simple cross-study
comparisons and a meta-analysis of variance-accounted-for effect sizes would
generally be irrational unless differences in research designs are explicitly
considered.
PMID- 27503195
TI - Abstract-concept learning in Black-billed magpies (Pica hudsonia).
AB - relational concepts depend upon relationships between stimuli (e.g., same vs.
different) and transcend features of the training stimuli. Recent evidence shows
that learning abstract concepts is shared across a variety species including
birds. Our recent work with a highly-skilled food-storing bird, Clark's
nutcracker, revealed superior same/different abstract-concept learning compared
to rhesus monkeys, capuchin monkeys, and pigeons. Here we test a more social, but
less reliant on food-storing, corvid species, the Black-billed magpie (Pica
hudsonia). We used the same procedures and training exemplars (eight pairs of the
same rule, and 56 pairs of the different rule) as were used to test the other
species. Magpies (n = 10) showed a level of abstract-concept learning that was
equivalent to nutcrackers and greater than the primates and pigeons tested with
these same exemplars. These findings suggest that superior initial abstract
concept learning abilities may be shared across corvids generally, rather than
confined to those strongly reliant on spatial memory.
PMID- 27503196
TI - Removing Cardiac Artefacts in Magnetoencephalography with Resampled Moving
Average Subtraction.
AB - Magnetoencephalography (MEG) signals are commonly contaminated by cardiac
artefacts (CAs). Principle component analysis and independent component analysis
have been widely used for removing CAs, but they typically require a complex
procedure for the identification of CA-related components. We propose a simple
and efficient method, resampled moving average subtraction (RMAS), to remove CAs
from MEG data. Based on an electrocardiogram (ECG) channel, a template for each
cardiac cycle was estimated by a weighted average of epochs of MEG data over
consecutive cardiac cycles, combined with a resampling technique for accurate
alignment of the time waveforms. The template was subtracted from the
corresponding epoch of the MEG data. The resampling reduced distortions due to
asynchrony between the cardiac cycle and the MEG sampling times. The RMAS method
successfully suppressed CAs while preserving both event-related responses and
high-frequency (>45 Hz) components in the MEG data.
PMID- 27503197
TI - [Health as a commodity : The deprofessionalization of physicians].
AB - The German health care delivery system is increasingly drawn into the framework
and profit expectations of an industrial economic system. This development is one
of the consequences of global political and economic restructuring, and can
hardly be influenced by national health policy. Physicians are marginalized.
Their professional work is reduced to certain core activities, often directed by
commercial interests.
PMID- 27503198
TI - Survival of Del17p CLL Depends on Genomic Complexity and Somatic Mutation.
AB - PURPOSE: Chronic lymphocytic leukemia (CLL) with 17p deletion typically
progresses quickly and is refractory to most conventional therapies. However,
some del(17p) patients do not progress for years, suggesting that del(17p) is not
the only driving event in CLL progression. We hypothesize that other concomitant
genetic abnormalities underlie the clinical heterogeneity of del(17p) CLL.
EXPERIMENTAL DESIGN: We profiled the somatic mutations and copy number
alterations (CNA) in a large group of del(17p) CLLs as well as wild-type CLL and
analyzed the genetic basis of their clinical heterogeneity. RESULTS: We found
that increased somatic mutation number associates with poor overall survival
independent of 17p deletion (P = 0.003). TP53 mutation was present in 81% of
del(17p) CLL, mostly clonal (82%), and clonal mutations with del(17p) exhibit
shorter overall survival than subclonal mutations with del(17p) (P = 0.019).
Del(17p) CLL has a unique driver mutation profile, including NOTCH1 (15%), RPS15
(12%), DDX3X (8%), and GPS2 (6%). We found that about half of del(17p) CLL cases
have recurrent deletions at 3p, 4p, or 9p and that any of these deletions
significantly predicts shorter overall survival. In addition, the number of CNAs,
but not somatic mutations, predicts shorter time to treatment among patients
untreated at sampling. Indolent del(17p) CLLs were characterized by absent or
subclonal TP53 mutation and few CNAs, with no difference in somatic mutation
number. CONCLUSIONS: We conclude that del(17p) has a unique genomic profile and
that clonal TP53 mutations, 3p, 4p, or 9p deletions, and genomic complexity are
associated with shorter overall survival. Clin Cancer Res; 23(3); 735-45. (c)2016
AACR.
PMID- 27503199
TI - Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3
Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling
Pathway.
AB - PURPOSE: Loss of Chr9q31-33 is one of the most common chromosome imbalances of
cervical cancer, but the underlying mechanism has not been well documented.
EXPERIMENTAL DESIGN: The loss of heterozygosity (LOH) status of Chr9q31-33 was
investigated utilizing 26 microsatellite markers. We detected the expression of
miR-181a2/181b2 by qRT-PCR analysis of cervical cancer cell lines and 100 paired
tumor samples and corresponding adjacent non-tumor tissues. Kaplan-Meier and Cox
proportional hazard regression analyses were performed to identify the prognostic
value of miR-181a2/181b2. Regulation of expression was analyzed by methylation
specific PCR. The tumor-suppressing effects of miR-181a2/181b2 were determined in
vitro and in vivo The target gene and signaling pathway that mediated the
function of miR-181a2/181b2 were also identified. RESULTS: Chr9q33.3 was
identified as one of the most deleted regions in cervical cancer. Underexpression
of miR-181a2/181b2 was detected in 46% of cervical cancer and was induced by the
LOH of chr9q33.3 and promoter hypermethylation. Attenuated miR-181a2/181b2
expression predicted a poor prognostic phenotype and advanced clinical stage of
cervical cancer. miR-181a2/181b2 prominently dampened cell-cycle progression,
suppressed cell growth, and promoted apoptosis of tumor cells in vitro They also
effectively impeded tumor formation and growth in vivo miR-181a2/181b2 exert the
tumor suppressor ability by depressing the direct target PIK3R3 (p55gamma) and
consequently modulating the PIK3R3/Akt/FoxO signaling pathway. CONCLUSIONS: We
demonstrated a cause-and-effect event beginning from loss of chr9q33.3, a
frequent event in cervical cancer, to the underexpression of miR-181a2/181b2,
leading to the elevated activation of the PI3K pathway. Clin Cancer Res; 23(2);
575-86. (c)2016 AACR.
PMID- 27503201
TI - e-Corrigendum.
PMID- 27503202
TI - Galagos as avian nest predators in South Africa.
AB - Galagos are generally regarded as dietary specialists that feed predominantly on
insects and gum. The diet of the thick-tailed greater galago is more varied and
also includes fruit and small vertebrates, although the latter is rare and
restricted to certain populations. The southern lesser galago is seemingly a more
specialist forager, but frugivory was recently reported in two separate
populations, suggesting at least some dietary plasticity in this species. The
species is not known to consume vertebrates. Here I report on observations of
avian nest predation by both thick-tailed greater and southern lesser galagos in
Roodewal State Forest Reserve in South Africa. Galagos were responsible for 56 %
of nest losses captured on trail cameras. Both species consumed eggs and
nestlings of six species of passerines ranging in size from recently hatched to
~30 g nestlings almost ready to fledge. The consumption of vertebrates by the
southern lesser galago represents an extension of its diet, as this has not been
reported before. The results suggest that eggs and nestlings comprise part of the
regular diet of thick-tailed greater galagos in the study area, albeit only
seasonal. The consumption of vertebrate prey by southern lesser galagos may
represent the expression of latent behavior which is only expressed under certain
environmental conditions, e.g., a severe drought, when its regular food base may
be diminished.
PMID- 27503200
TI - A Phase 1 Study of the PARP Inhibitor Veliparib in Combination with Temozolomide
in Acute Myeloid Leukemia.
AB - PURPOSE: In preclinical studies, the PARP inhibitor veliparib enhanced the
antileukemic action of temozolomide through potentiation of DNA damage.
Accordingly, we conducted a phase 1 study of temozolomide with escalating doses
of veliparib in patients with relapsed, refractory acute myeloid leukemia (AML)
or AML arising from aggressive myeloid malignancies. EXPERIMENTAL DESIGN:
Patients received veliparib [20-200 mg once a day on day 1 and twice daily on
days 4-12 in cycle 1 (days 1-8 in cycle >=2)] and temozolomide [150-200 mg/m2
daily on days 3-9 in cycle 1 (days 1-5 in cycle >=2)] every 28 to 56 days.
Veliparib pharmacokinetics and pharmacodynamics [ability to inhibit poly(ADP
ribose) polymer (PAR) formation and induce H2AX phosphorylation] were assessed.
Pretreatment levels of MGMT and PARP1 protein, methylation of the MGMT promoter,
and integrity of the Fanconi anemia pathway were also examined. RESULTS: Forty
eight patients were treated at seven dose levels. Dose-limiting toxicities were
oral mucositis and esophagitis lasting >7 days. The MTD was veliparib 150 mg
twice daily with temozolomide 200 mg/m2 daily. The complete response (CR) rate
was 17% (8/48 patients). Veliparib exposure as well as inhibition of PAR polymer
formation increased dose proportionately. A veliparib-induced increase in H2AX
phosphorylation in CD34+ cells was observed in responders. Three of 4 patients
with MGMT promoter methylation achieved CR. CONCLUSIONS: Veliparib plus
temozolomide is well tolerated, with activity in advanced AML. Further evaluation
of this regimen and of treatment-induced phosphorylation of H2AX and MGMT
methylation as potential response predictors appears warranted. Clin Cancer Res;
23(3); 697-706. (c)2016 AACR.
PMID- 27503205
TI - Correlation between the serum levels of type IV collagen 7s domain and the risk
of intractable ascites following liver resection for hepatocellular carcinoma: A
propensity score-matched analysis.
AB - BACKGROUND: The severity of liver fibrosis has been reported to be correlated
with the risk of intractable ascites after hepatectomy for hepatocellular
carcinoma. Since 2009, we have measured routinely the serum concentrations of
type IV collagen 7s domain (7s collagen), a biochemical marker of liver fibrosis
and applied limited resection to patients with elevation of the serum 7s collagen
concentrations above the upper limit of normal (6.0 ng/mL). The aim of this study
was to assess the potential benefits of our treatment strategy on the
postoperative outcomes of patients with hepatocellular carcinoma. METHODS: A
propensity score-matched analysis was performed to compare the outcomes between
patients who underwent initial hepatectomy for hepatocellular carcinoma before or
after 2009 (2009 to April 2015; period 2) and those who underwent the operation
prior to 2009 (1990-2008; period 1; n = 129 in each period). RESULTS: The
incidence of intractable ascites was significantly lower in period 2 than in
period 1 (2.3 vs 14.7%; P < .001), although the other short-term and long-term
outcomes were comparable between the 2 groups. A multivariate analysis identified
elevation of the serum 7s collagen concentrations to >=7.4 ng/mL as an
independent predictor of IA (odds ratio 14.1, 95% confidence interval 2.8 to
106.7; P = .001), with the area under the receiver-operating characteristic curve
of 0.820 (0.648-0.919, P = .005). CONCLUSION: Modification of the surgical
procedure according to the serum 7s collagen concentration is beneficial for
reducing the risk of development of intractable ascites after hepatectomy for
hepatocellular carcinoma.
PMID- 27503203
TI - Zebrafish models of cardiovascular disease.
AB - Cardiovascular disease (CVD) is one of the leading causes of death worldwide. The
most significant risk factors associated with the development of heart diseases
include genetic and environmental factors such as hypertension, high blood
cholesterol levels, diabetes, smoking, and obesity. Coronary artery disease
accounts for the highest percentage of CVD deaths and stroke, cardiomyopathies,
congenital heart diseases, heart valve defects and arrhythmias follow. The
causes, prevention, and treatment of all forms of cardiovascular disease remain
active fields of biomedical research, with hundreds of scientific studies
published on a weekly basis. Generating animal models of cardiovascular diseases
is the main approach used to understand the mechanism of pathogenesis and also
design and test novel therapies. Here, we will focus on recent advances to
finding the genetic cause and the molecular mechanisms of CVDs as well as novel
drugs to treat them, using a small tropical freshwater fish native to Southeast
Asia: the zebrafish (Danio rerio). Zebrafish emerged as a high-throughput but low
cost model organism that combines the advantages of forward and reverse genetics
with phenotype-driven drug screenings. Noninvasive imaging allows in vivo
analyses of cardiovascular phenotypes. Functional verification of candidate genes
from genome-wide association studies has verified the role of several genes in
the pathophysiology of CVDs. Also, zebrafish hearts maintain their ability to
regenerate throughout their lifetime, providing novel insights to understand
human cardiac regeneration.
PMID- 27503204
TI - Therapeutic Potential of Secreted Molecules Derived from Human Amniotic Fluid
Mesenchymal Stem/Stroma Cells in a Mice Model of Colitis.
AB - Inflammatory bowel diseases (IBDs) are the result of pathological immune
responses due to environmental factors or microbial antigens into a genetically
predisposed individual. Mainly due to their trophic properties, a mounting
interest is focused on the use of human mesenchymal stem/stromal cells (hMSCs) to
treat IBD disease in animal models. The aim of the study is to test whether the
secreted molecules, derived from a specific population of second trimester
amniotic fluid mesenchymal stem/stromal cells, the spindle-shaped MSCs (SS-AF
MSCs), could be utilized as a novel therapeutic, cell free approach for IBD
therapy. Induction of colitis was achieved by oral administration of dextran
sulphate sodium (DSS) (3 % w/v in tap water), for 5 days, to 8-week-old NOD/SCID
mice. The progression of colitis was assessed on a daily basis through recording
the body weight, stool consistency and bleeding. Conditioned media (CM) derived
from SS-AF-MSCs were collected, concentrated and then delivered intraperitoneally
into DSS treated mice. To evaluate and determine the inflammatory cytokine
levels, histopathological approach was applied. Administration of CM derived from
SS-AF-MSCs cells reduced the severity of colitis in mice. More importantly, TGFb1
protein levels were increased in the mice received CM, while TNFa and MMP2
protein levels were decreased, respectively. Accordingly, IL-10 was significantly
increased in mice received CM, whereas TNFa and IL-1b were decreased at mRNA
level. Our results demonstrated that CM derived from SS-AF-MSCs cells is able to
ameliorate DSS-induced colitis in immunodeficient colitis mouse model, and thus,
it has a potential for use in IBD therapy.
PMID- 27503206
TI - An Online Learning Module to Increase Self-Efficacy and Involvement in Care for
Patients With Advanced Lung Cancer: Research Protocol.
AB - BACKGROUND: Improving patient care for individuals with lung cancer is a priority
due to the increasing burden of the disease globally. One way this can be done is
by improving patient self-management capabilities through increasing their self
efficacy. This can improve positive outcomes for patients with chronic conditions
and increase their ability to manage the challenges of such illnesses.
Unfortunately, patients with chronic conditions often struggle to travel far from
home to engage with patient education events, a common means of improving self
efficacy. The development of more accessible tools for improving patient self
efficacy is required to increase quality of life for patients with chronic
conditions. OBJECTIVE: To evaluate the feasibility of delivering symptom
identification and management information to patients with advanced lung cancer
using an online program. METHODS: This article describes a pre-post test study to
evaluate a Qstream online learning platform to improve patient self-efficacy for
managing advanced lung cancer symptoms. Undertaking this program should increase
participant knowledge about the side-effects they may experience as a result of
their treatment and in turn increase help-seeking behavior and self-efficacy for
the participant cohort. Quantitative data collected by the Qstream platform on
the completion rates of participants will be used as a tool to evaluate the
intervention. Additionally, validated scales will be used to collect data on
patient self-efficacy. Qualitative data will also be collected via an exit survey
and thematic content analysis of semi-structured interviews. RESULTS: The
research is in the preliminary stages but thus far a protocol has been approved
in support of the project. Additionally, advisory committee members have been
identified and initial meetings have been undertaken. CONCLUSIONS: Development of
new approaches for increasing patient understanding of their care is important to
ensure high quality care continues to be delivered in the clinical setting.
PMID- 27503207
TI - Single or dual experimental infections with Vibrio aestuarianus and OsHV-1 in
diploid and triploid Crassostrea gigas at the spat, juvenile and adult stages.
AB - French production of the Pacific cupped oyster, Crassostrea gigas, is currently
threatened by two pathogens, OsHV-1 and V. aestuarianus. While oysters selected
for their higher resistance to OsHV-1 are now available for the industry, the
impact of V. aestuarianus on such oysters is unknown, especially for triploids.
In addition, experimental infection has used the virus or the bacteria alone, but
there have been no investigations of dual exposure to these pathogens. This study
is the first report of single or dual exposure in spat (Spat1 and Spat2),
juvenile and adult naive oysters. For each of the two stocks evaluated,
unselected oysters and oysters selected for their higher resistance to OsHV-1
infection were tested, as well as their triploid siblings of the selected oysters
produced using cytochalasin B. We confirmed that resistance to OsHV-1 infection
and susceptibility to V. aestuarianus increased with age and size, although
selected oysters were not significantly impacted by OsHV-1 whatever their ploidy,
size or age. We found different mortality patterns depending on the pathogen
tested. The mortality pattern was similar for oysters exposed to OsHV-1 or to
both pathogens in the Spat1 trial (4months old and 1.9g). The mortality pattern
was similar for oysters exposed to V. aestuarianus or to both pathogens in the
Adult trial (25months old and 63.1g). Surprisingly, mortality was much higher
(ranging from 75.9% to 100%), in particular for the selected oysters, for the
Spat2 (8months old/3.9g) and Juvenile trials (16months old/18.4g) given a dual
exposure, regardless of the level of selection for OsHV-1 and the ploidy state.
Our findings highlight an important threat for oyster farmers: oysters exposed to
both pathogens could experience dramatic mortality rates, even in oysters
selected for their higher resistance to OsHV-1. Finally, our study demonstrated
for the first time that triploid oysters were more susceptible to experimental
challenges with V. aestuarianus at the spat stage than their diploid siblings.
However, the difference in mortality between the triploids and diploids remained
limited and ranged from 22.9% to 6.6% for spat and adults, respectively with a
relatively regularly decrease in the difference with increased age.
PMID- 27503208
TI - Immunotherapy Expands and Maintains the Function of High-Affinity Tumor
Infiltrating CD8 T Cells In Situ.
AB - Cancer cells harbor high-affinity tumor-associated Ags capable of eliciting
potent antitumor T cell responses, yet detecting these polyclonal T cells is
challenging. Therefore, surrogate markers of T cell activation such as CD69,
CD44, and programmed death-1 (PD-1) have been used. We report in this study that
in mice, expression of activation markers including PD-1 is insufficient in the
tumor microenvironment to identify tumor Ag-specific T cells. Using the Nur77GFP
T cell affinity reporter mouse, we highlight that PD-1 expression can be induced
independent of TCR ligation within the tumor. Given this, we characterized the
utility of the Nur77GFP model system in elucidating mechanisms of action of
immunotherapies independent of PD-1 expression. Coexpression of Nur77GFP and OX40
identifies a polyclonal population of high-affinity tumor-associated Ag-specific
CD8(+) T cells, which produce more IFN-gamma in situ than OX40 negative and
doubles in quantity with anti-OX40 and anti-CTLA4 mAb therapy but not with anti
PD-1 or programmed death ligand-1. Moreover, expansion of these high-affinity CD8
T cells prolongs survival of tumor-bearing animals. Upon chronic stimulation in
tumors and after adoptive cell therapy, CD8 TCR signaling and Nur77GFP induction
is impaired, and tumors progress. However, this can be reversed and overall
survival significantly enhanced after adoptive cell therapy with agonist OX40
immunotherapy. Therefore, we propose that OX40 agonist immunotherapy can maintain
functional TCR signaling of chronically stimulated tumor-resident CD8 T cells,
thereby increasing the frequency of cytotoxic, high-affinity, tumor-associated Ag
specific cells.
PMID- 27503210
TI - lck-Driven Cre Expression Alters T Cell Development in the Thymus and the
Frequencies and Functions of Peripheral T Cell Subsets.
AB - Conditional gene targeting using the bacteriophage-derived Cre recombinase is
widely applied for functional gene studies in mice. Mice transgenic for Cre under
the control of the lck gene promoter are used to study the role of loxP-targeted
genes in T cell development and function. In this article, we show a striking 65%
reduction in cellularity, preferential development of gammadelta versus alphabeta
T cells, and increased expression of IL-7R in the thymus of mice expressing Cre
under the proximal lck promoter (lck-cre(+) mice). The transition from CD4/CD8
double-negative to double-positive cells was blocked, and lck-cre(+) double
positive cells were more prone to apoptosis and showed higher levels of Cre
expression. Importantly, numbers of naive T cells were reduced in spleens and
lymph nodes of lck-cre(+) mice. In contrast, frequencies of gammadelta T cells,
CD44(+)CD62L(-) effector T cells, and Foxp3(+) regulatory T cells were elevated,
as was the frequency of IFN-gamma-secreting CD4(+) and CD8(+) T cells. A
literature survey of 332 articles that used lck-cre(+) mice for deletion of
floxed genes indicated that results are statistically influenced by the control
used (lck-cre(+) or lck-cre(-)), more frequently resembling the lck-cre(+)
phenotype described in this article if lck-cre(-) controls were used. Altogether,
care should be taken when interpreting published results and to properly control
targeted gene deletions using the lck-cre(+) strain.
PMID- 27503209
TI - TLR2 Activation Limits Rhinovirus-Stimulated CXCL-10 by Attenuating IRAK-1
Dependent IL-33 Receptor Signaling in Human Bronchial Epithelial Cells.
AB - Airway epithelial cells are the major target for rhinovirus (RV) infection and
express proinflammatory chemokines and antiviral cytokines that play a role in
innate immunity. Previously, we demonstrated that RV interaction with TLR2 causes
ILR-associated kinase-1 (IRAK-1) depletion in both airway epithelial cells and
macrophages. Further, IRAK-1 degradation caused by TLR2 activation was shown to
inhibit ssRNA-induced IFN expression in dendritic cells. Therefore, in this
study, we examined the role of TLR2 and IRAK-1 in RV-induced IFN-beta, IFN
lambda1, and CXCL-10, which require signaling by viral RNA. In airway epithelial
cells, blocking TLR2 enhanced RV-induced expression of IFNs and CXCL-10. By
contrast, IRAK-1 inhibition abrogated RV-induced expression of CXCL-10, but not
IFNs in these cells. Neutralization of IL-33 or its receptor, ST2, which requires
IRAK-1 for signaling, inhibited RV-stimulated CXCL-10 expression. In addition, RV
induced expression of both ST2 and IL-33 in airway epithelial cells. In
macrophages, however, RV-stimulated CXCL-10 expression was primarily dependent on
TLR2/IL-1R. Interestingly, in a mouse model of RV infection, blocking ST2 not
only attenuated RV-induced CXCL-10, but also lung inflammation. Finally,
influenza- and respiratory syncytial virus-induced CXCL-10 was also found to be
partially dependent on IL-33/ST2/IRAK-1 signaling in airway epithelial cells.
Together, our results indicate that RV stimulates CXCL-10 expression via the IL
33/ST2 signaling axis, and that TLR2 signaling limits RV-induced CXCL-10 via IRAK
1 depletion at least in airway epithelial cells. To our knowledge, this is the
first report to demonstrate the role of respiratory virus-induced IL-33 in the
induction of CXCL-10 in airway epithelial cells.
PMID- 27503211
TI - TLR Tolerance as a Treatment for Central Nervous System Autoimmunity.
AB - The role of TLR signaling in multiple sclerosis (MS) and experimental autoimmune
encephalomyelitis (EAE) is unclear. This role is especially controversial in
models of adoptive transfer EAE in which no adjuvant and no TLR ligands are
administered. We recently reported that a microbiome-derived TLR2 ligand, Lipid
654 (L654), is present in healthy human serum but significantly decreased in the
serum of MS patients. This suggested that microbiome products that gain access to
the systemic circulation, rather than being proinflammatory, may normally play an
immune-regulatory role by maintaining a state of relative TLR tolerance.
Therefore, a loss of microbiome-mediated TLR tolerance, as suggested by lower
serum levels of L654, may play a role in the pathogenesis of MS. As proof of
concept we asked whether administering low-level TLR2 ligands in adoptive
transfer EAE induces TLR2 tolerance and attenuates disease. We administered low
level Pam2CSK4 or L654 to mice receiving encephalitogenic cells and in doing so
induced both TLR2 tolerance and attenuation of EAE. Disease attenuation was
accompanied in the CNS by a decrease in macrophage activation, a decrease in a
specific proinflammatory macrophage population, and a decrease in Th17 cells. In
addition, disease attenuation was associated with an increase in splenic type 1
regulatory T cells. Kinetic tolerance induction studies revealed a critical
period for TLR2 involvement in adoptive transfer EAE. Overall, these results
suggest that inducing TLR tolerance may offer a new approach to treating CNS
autoimmune diseases such as MS.
PMID- 27503212
TI - The Effect of Bariatric Surgery on Mobility, Health-Related Quality of Life,
Healthcare Resource Utilization, and Employment Status.
AB - BACKGROUND: A sub-study of the Ontario Bariatric Registry was conducted to
evaluate the impact of bariatric surgery on mobility, health-related quality of
life (HRQoL), healthcare resource utilization (HRU), and employment status.
METHODS: The 1-year change in mobility following bariatric surgery was evaluated
using the mobility domain of the EuroQOL-5D-5L (EQ-5D-5L), which was self
administered at baseline and 1 year after bariatric surgery along with questions
on HRU. Another questionnaire was used to document employment status at time of
surgery and 1 year later. RESULTS: The population included 304 individuals (mean
age = 46 years; 85 % female). At baseline, 68 % of participants had some problems
in walking compared to 14 % at 1 year following surgery (p < 0.001). The EQ-5D-5L
health utility score increased from 0.73 to 0.90 (p < 0.001). The number of
hospitalizations increased significantly before and after surgery (p = 0.021). Of
the 304 study participants, 138 completed the questionnaire and responses
indicated that more individuals reported a change in their employment status
within 1 year following surgery (26 %) compared to 1 year prior to the surgery (9
%) (p < 0.001). CONCLUSIONS: Within the limitations of this study, there is a
suggestion that bariatric surgery has a major impact on mobility and HRQoL. More
research is warranted to understand the benefits, costs, and cost-effectiveness
of bariatric surgery in Canada.
PMID- 27503213
TI - Internal Cardioverter Defibrillator Indications and Therapies after Atrial Baffle
Procedure for d-Transposition of the Great Arteries: A Multicenter Analysis.
AB - BACKGROUND: Sudden cardiac death (SCD) is the most important cause of late
mortality after atrial baffle procedure for d-transposition of the great arteries
(d-TGA). Experience with internal cardioverter defibrillator (ICD) therapy in
this population is limited. We conducted a multicenter cohort study to determine
the current state of ICD therapy in individuals after atrial baffle procedure.
METHODS: Demographic and clinical data as well as data on device implantation,
programming, ICD discharges, and complications after atrial baffle procedure for
d-TGA from four German centers were analyzed retrospectively. RESULTS: ICD
implantation was undertaken in 33 subjects. ICD implantation was undertaken as
primary prevention in 29 (88%) and secondary prevention in four (12%)
individuals. There were 21 (64%) subjects with atrial reentrant tachycardia
(IART). During a median follow-up of 4.8 years, seven appropriate ICD therapies
were delivered in three (10%) individuals with primary prevention indication. No
appropriate shocks were documented in subjects with secondary prevention
indication. A total of 12 inappropriate ICD discharges occurred in eight (24%)
individuals due to IART (n = 6) or lead failure (n = 2). ICD-related
complications were noted in seven individuals (21%): lead dislodgement/failure in
five (15%) and ICD infection in two subjects (6%). CONCLUSIONS: The majority of
individuals received an ICD for primary prevention of SCD, thus representing a
liberal attitude of physicians for ICD implantation. During a median follow-up of
4.8 years, the rate of appropriate ICD therapies was low and clearly exceeded by
inappropriate ICD discharges. Lead failure and IART were present in >20% of the
individuals and were frequent reasons for inappropriate ICD discharges. Facing
these results, rigorous treatment of IART and careful ICD programming seems
mandatory.
PMID- 27503214
TI - Excessive bleeding is a normal cleansing process: a qualitative study of
postpartum haemorrhage among rural Uganda women.
AB - BACKGROUND: Postpartum haemorrhage (PPH) remains the leading cause of maternal
morbidity and mortality worldwide. The main strategy for preventing PPH is the
use of uterotonic drugs given prophylactically by skilled health workers.
However, in settings where many women still deliver at home without skilled
attendants, uterotonics are often inaccessible. In such cases, women and their
caregivers need to recognize PPH promptly so, as to seek expert care. For this
reason, it is important to understand how women and their caregivers recognize
PPH, as well as the actions they undertake to prevent and treat PPH in home
births. Such knowledge can also inform programs aiming to make uterotonics
accessible at the community level. METHODS: Between April and June 2012, a
phenomenological study was carried out in a rural Ugandan district involving 15
in-depth interviews. Respondents were purposively sampled and included six women
who had delivered at home in the past year and nine traditional birth attendants
(TBAs). The interviews explored how PPH was recognized, its perceived causes, and
the practices that respondents used in order to prevent or treat it.
Phenomenological descriptive methodology was used to analyse the data. RESULTS:
Bleeding after childbirth was considered to be a normal cleansing process, which
if stopped or inhibited would lead to negative health consequences to the mother.
Respondents used a range of criteria to recognize PPH: rate of blood flow, amount
of blood (equivalent to two clenched fists), fainting, feeling thirsty,
collapsing or losing consciousness immediately after birth. As a group,
respondents seemed to correctly identify women at risk of PPH (those with twin
pregnancies, high parity or prolonged labour), but many individuals did not know
all the reasons. Respondents used cold drink, uterine massage and traditional
medicine to treat PPH. CONCLUSION: The community viewed bleeding after childbirth
as a normal process and their methods of determining excessive bleeding are
imprecise and varied. This opens the door for intervention for reducing delays in
the home diagnosis of PPH. This includes increasing awareness among TBAs, women
and their families about the risk of death due to excessive bleeding in the
immediate postpartum period.
PMID- 27503215
TI - The impact of positive, negative and neutral stimuli in a virtual reality
cognitive-motor rehabilitation task: a pilot study with stroke patients.
AB - BACKGROUND: Virtual Reality (VR) based methods for stroke rehabilitation have
mainly focused on motor rehabilitation, but there is increasing interest in
integrating motor and cognitive training to increase similarity to real-world
settings. Unfortunately, more research is needed for the definition of which type
of content should be used in the design of these tools. One possibility is the
use of emotional stimuli, which are known to enhance attentional processes.
According to the Socioemotional Selectivity Theory, as people age, the emotional
salience arises for positive and neutral, but not for negative stimuli. METHODS:
For this study we developed a cognitive-motor VR task involving attention and
short-term memory, and we investigated the impact of using emotional images of
varying valence. The task consisted of finding a target image, shown for only two
seconds, among fourteen neutral distractors, and selecting it through arm
movements. After performing the VR task, a recall task took place and the
patients had to identify the target images among a valence-matched number of
distractors. Ten stroke patients participated in a within-subjects experiment
with three conditions based on the valence of the images: positive, negative and
neutral. Eye movements were recorded during VR task performance with an eye
tracking system. RESULTS: Our results show decreased attention for negative
stimuli in the VR task performance when compared to neutral stimuli. The recall
task shows significantly more wrongly identified images (false memories) for
negative stimuli than for neutral. Regression and correlation analyses with the
Montreal Cognitive Assessment and the Geriatric Depression Scale revealed
differential effects of cognitive function and depressive symptomatology in the
encoding and recall of positive, negative and neutral images. Further, eye
movement data shows reduced search patterns for wrongly selected stimuli
containing emotional content. CONCLUSIONS: The results of this study suggest that
it is feasible to use emotional content in a VR based cognitive-motor task for
attention and memory training after stroke. Stroke survivors showed less
attention towards negative information, exhibiting reduced visual search patterns
and more false memories. We have also shown that the use of emotional stimuli in
a VR task can provide additional information regarding patient's mood and
cognitive status.
PMID- 27503216
TI - Auxin Influx Carrier AUX1 Confers Acid Resistance for Arabidopsis Root Elongation
Through the Regulation of Plasma Membrane H+-ATPase.
AB - The plant plasma membrane (PM) H+-ATPase regulates pH homeostasis and cell
elongation in roots through the formation of an electrochemical H+ gradient
across the PM and a decrease in apoplastic pH; however, the detailed signaling
for the regulation of PM H+-ATPases remains unclear. Here, we show that an auxin
influx carrier, AUXIN RESISTANT1 (AUX1), is required for the maintenance of PM H+
ATPase activity and proper root elongation. We isolated a low pH-hypersensitive 1
(loph1) mutant by a genetic screen of Arabidopsis thaliana on low pH agar plates.
The loph1 mutant is a loss-of-function mutant of the AUX1 gene and exhibits a
root growth retardation restricted to the low pH condition. The ATP hydrolysis
and H+ extrusion activities of the PM H+-ATPase were reduced in loph1 roots.
Furthermore, the phosphorylation of the penultimate threonine of the PM H+-ATPase
was reduced in loph1 roots under both normal and low pH conditions without
reduction of the amount of PM H+-ATPase. Expression of the DR5:GUS reporter gene
and auxin-responsive genes suggested that endogenous auxin levels were lower in
loph1 roots than in the wild type. The aux1-7 mutant roots also exhibited root
growth retardation in the low pH condition like the loph1 roots. These results
indicate that AUX1 positively regulates the PM H+-ATPase activity through
maintenance of the auxin accumulation in root tips, and this process may serve to
maintain root elongation especially under low pH conditions.
PMID- 27503217
TI - The Pepper RING-Type E3 Ligase, CaAIP1, Functions as a Positive Regulator of
Drought and High Salinity Stress Responses.
AB - Plant adaptive responses to osmotic stress are co-ordinated by restriction of
growth and developmental processes and by molecular and physiological activities.
The phytohormone ABA is the primary regulator that induces and responds to
osmotic stress, and its sensitivity markedly influences osmotic stress tolerance
levels. Several E3 ubiquitin ligases act as positive or negative regulators of
ABA, thereby mediating sensitivity to osmotic stress in higher plants. Here, we
report that the C3H2C3-type RING finger E3 ligase, CaAIP1, regulates osmotic
stress responses via ABA-mediated signaling. CaAIP1 contains a RING finger motif,
which functions during attachment of ubiquitins to the target proteins.
Expression of CaAIP1 was induced by ABA, drought and NaCl treatments, suggesting
its role in the osmotic stress response. CaAIP1-silenced pepper plants displayed
a drought-sensitive phenotype characterized by a high level of transpirational
water loss in the drought-treated leaves. CaAIP1-overexpressing (OX) plants
exhibited increased sensitivity to ABA, but an NaCl- and mannitol-tolerant
phenotype during seed germination and seedling growth. CaAIP1-OX plants further
displayed enhanced tolerance to drought stress, characterized by low levels of
transpirational water loss via increased stomatal closure and leaf temperature.
Our data indicate that CaAIP1 is a positive regulator of the osmotic stress
tolerance mechanism.
PMID- 27503218
TI - Sperm motility and morphology changes in rats exposed to cadmium and diazinon.
AB - BACKGROUND: Humans are ubiquitously exposed to multiple environmental
contaminants. Consequences of combined action on the reproductive system remain
unknown. This study aimed to assess single and joint effects of cadmium and
diazinon exposure on sperm quality parameters. METHODS: Male adult Wistar rats
were randomized into 4 groups of ten animals each. Group A was used as a control,
animals from group B were exposed to cadmium (30 mg/L), rats from group C were
administered with diazinon (40 mg/L), and rats from group D were exposed
simultaneously to cadmium (30 mg/L) and diazinon (40 mg/L) via drinking water for
90 days. Sperm morphology and motility were evaluated using a bright field
microscope and a computer-assisted semen analysis. RESULTS: The percentage of
motile spermatozoa and morphologically normal sperm was markedly reduced in rats
from the group B. Rats from the C group showed an increase in velocity
parameters, amplitude of lateral head displacement, decrease in beat-cross
frequency, and an increase in abnormal sperm morphology. Simultaneous coexposure
to cadmium and diazinon increased distance and velocity parameters, and amplitude
of lateral head displacement. Reductions were observed in straightness,
linearity, wobble, and beat-cross frequency. The decreased normal sperm
morphology rates were related to defects of the sperm tail. CONCLUSIONS: Exposure
to cadmium and diazinon at relatively low doses impairs sperm quality and can
reduce male fertility. Cadmium and diazinon caused significant changes on sperm
morphology with varying effects on motility patterns. These parameters were
significantly higher in the group D as compared to the group C. The findings have
important implications for reproductive risk assessment of combined exposures to
multiple chemicals.
PMID- 27503220
TI - Leena Peltonen-Palotie: 1952-2010.
PMID- 27503219
TI - Chelatococcus reniformis sp. nov., isolated from a glacier.
AB - A Gram-stain-negative, non-motile, reniform bacterial strain, B2974T, was
isolated from an ice core of the Muztagh Glacier, on the Tibetan Plateau, China.
Strain B2974T grew optimally at pH 7.0-7.5 and 25-30 degrees C in the presence
of 0-2.0 % (w/v) NaCl. 16S rRNA gene sequence similarity analysis indicated that
strain B2974T was closely related to Chelatococcus asaccharovorans LMG 25503T at
a level of 97.1 %. The major quinone of strain B2974T was ubiquinone Q10. The
predominant fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 :
1omega6c) and C19 : 0 cyclo omega8c. sym-Homospermidine was the major polyamine.
The genomic DNA G+C content of the strain was 64 mol%. In DNA-DNA hybridization
tests, strain B2974T shared 49.32 % DNA-DNA relatedness with the type strain of
Chelatococcus asaccharovorans LMG 25503T. Based on the results of phenotypic and
chemotaxonomic characteristics, strain B2974T was considered as a novel species
of the genus Chelatococcus, for which the name Chelatococcus reniformis sp. nov.
is proposed. The type strain is B2974T (=JCM 30308T=CGMCC 1.12919T).
PMID- 27503222
TI - BiDiFuse: a FIJI plugin for fusing bi-directionally recorded microscopic image
volumes.
AB - : Deep tissue imaging is increasingly used for non-destructive interrogation of
intact organs and small model organisms. An intuitive approach to increase the
imaging depth by almost a factor of 2 is to record a sample from two sides and
fuse both image stacks. However, imperfect three-dimensional alignment of both
stacks presents a computational challenge. We have developed a FIJI plugin,
called BiDiFuse, which merges bi-directionally recorded image stacks via 3D rigid
transformations. The method is broadly applicable, considering it is compatible
with all optical sectioning microscopes and it does not rely on fiducial markers
for image registration. AVAILABILITY AND IMPLEMENTATION: The method is freely
available as a plugin for FIJI from https://github.com/JanDetrez/BiDiFuse/
CONTACT: winnok.devos@uantwerpen.be.
PMID- 27503221
TI - A profile-based method for identifying functional divergence of orthologous genes
in bacterial genomes.
AB - MOTIVATION: Next generation sequencing technologies have provided us with a
wealth of information on genetic variation, but predicting the functional
significance of this variation is a difficult task. While many comparative
genomics studies have focused on gene flux and large scale changes, relatively
little attention has been paid to quantifying the effects of single nucleotide
polymorphisms and indels on protein function, particularly in bacterial genomics.
RESULTS: We present a hidden Markov model based approach we call delta-bitscore
(DBS) for identifying orthologous proteins that have diverged at the amino acid
sequence level in a way that is likely to impact biological function. We
benchmark this approach with several widely used datasets and apply it to a proof
of-concept study of orthologous proteomes in an investigation of host adaptation
in Salmonella enterica We highlight the value of the method in identifying
functional divergence of genes, and suggest that this tool may be a better
approach than the commonly used dN/dS metric for identifying functionally
significant genetic changes occurring in recently diverged organisms.
AVAILABILITY AND IMPLEMENTATION: A program implementing DBS for pairwise genome
comparisons is freely available at: https://github.com/UCanCompBio/deltaBS
CONTACT: nicole.wheeler@pg.canterbury.ac.nz or lars.barquist@uni
wuerzburg.deSupplementary information: Supplementary data are available at
Bioinformatics online.
PMID- 27503223
TI - Bayesian network feature finder (BANFF): an R package for gene network feature
selection.
AB - MOTIVATION: Network marker selection on genome-scale networks plays an important
role in the understanding of biological mechanisms and disease pathologies.
Recently, a Bayesian nonparametric mixture model has been developed and
successfully applied for selecting genes and gene sub-networks. Hence, extending
this method to a unified approach for network-based feature selection on general
large-scale networks and creating an easy-to-use software package is on demand.
RESULTS: We extended the method and developed an R package, the Bayesian network
feature finder (BANFF), providing a package of posterior inference, model
comparison and graphical illustration of model fitting. The model was extended to
a more general form, and a parallel computing algorithm for the Markov chain
Monte Carlo -based posterior inference and an expectation maximization-based
algorithm for posterior approximation were added. Based on simulation studies, we
demonstrate the use of BANFF on analyzing gene expression on a protein-protein
interaction network. AVAILABILITY: https://cran.r
project.org/web/packages/BANFF/index.html CONTACT: jiankang@umich.edu,
tianwei.yu@emory.eduSupplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 27503224
TI - PathScore: a web tool for identifying altered pathways in cancer data.
AB - : PathScore quantifies the level of enrichment of somatic mutations within
curated pathways, applying a novel approach that identifies pathways enriched
across patients. The application provides several user-friendly, interactive
graphic interfaces for data exploration, including tools for comparing pathway
effect sizes, significance, gene-set overlap and enrichment differences between
projects. AVAILABILITY AND IMPLEMENTATION: Web application available at
pathscore.publichealth.yale.edu. Site implemented in Python and MySQL, with all
major browsers supported. Source code available at:
github.com/sggaffney/pathscore with a GPLv3 license. CONTACT:
stephen.gaffney@yale.edu.
PMID- 27503225
TI - RNAcommender: genome-wide recommendation of RNA-protein interactions.
AB - MOTIVATION: Information about RNA-protein interactions is a vital pre-requisite
to tackle the dissection of RNA regulatory processes. Despite the recent advances
of the experimental techniques, the currently available RNA interactome involves
a small portion of the known RNA binding proteins. The importance of determining
RNA-protein interactions, coupled with the scarcity of the available information,
calls for in silico prediction of such interactions. RESULTS: We present
RNAcommender, a recommender system capable of suggesting RNA targets to
unexplored RNA binding proteins, by propagating the available interaction
information taking into account the protein domain composition and the RNA
predicted secondary structure. Our results show that RNAcommender is able to
successfully suggest RNA interactors for RNA binding proteins using little or no
interaction evidence. RNAcommender was tested on a large dataset of human RBP-RNA
interactions, showing a good ranking performance (average AUC ROC of 0.75) and
significant enrichment of correct recommendations for 75% of the tested RBPs.
RNAcommender can be a valid tool to assist researchers in identifying potential
interacting candidates for the majority of RBPs with uncharacterized binding
preferences. AVAILABILITY AND IMPLEMENTATION: The software is freely available at
http://rnacommender.disi.unitn.it CONTACT: gianluca.corrado@unitn.it or
andrea.passerini@unitn.itSupplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 27503226
TI - shinyGEO: a web-based application for analyzing gene expression omnibus datasets.
AB - : The Gene Expression Omnibus (GEO) is a public repository of gene expression
data. Although GEO has its own tool, GEO2R, for data analysis, evaluation of
single genes is not straightforward and survival analysis in specific GEO
datasets is not possible without bioinformatics expertise. We describe a web
application, shinyGEO, that allows a user to download gene expression data sets
directly from GEO in order to perform differential expression and survival
analysis for a gene of interest. In addition, shinyGEO supports customized
graphics, sample selection, data export and R code generation so that all
analyses are reproducible. The availability of shinyGEO makes GEO datasets more
accessible to non-bioinformaticians, promising to lead to better understanding of
biological processes and genetic diseases such as cancer. AVAILABILITY AND
IMPLEMENTATION: Web application and source code are available from
http://gdancik.github.io/shinyGEO/ CONTACT: dancikg@easternct.eduSupplementary
information: Supplementary data are available at Bioinformatics online.
PMID- 27503227
TI - SRinversion: a tool for detecting short inversions by splitting and re-aligning
poorly mapped and unmapped sequencing reads.
AB - MOTIVATION: Rapid development in sequencing technologies has dramatically
improved our ability to detect genetic variants in human genome. However, current
methods have variable sensitivities in detecting different types of genetic
variants. One type of such genetic variants that is especially hard to detect is
inversions. Analysis of public databases showed that few short inversions have
been reported so far. Unlike reads that contain small insertions or deletions,
which will be considered through gap alignment, reads carrying short inversions
often have poor mapping quality or are unmapped, thus are often not further
considered. As a result, the majority of short inversions might have been
overlooked and require special algorithms for their detection. RESULTS: Here, we
introduce SRinversion, a framework to analyze poorly mapped or unmapped reads by
splitting and re-aligning them for the purpose of inversion detection.
SRinversion is very sensitive to small inversions and can detect those less than
10 bp in size. We applied SRinversion to both simulated data and high-coverage
sequencing data from the 1000 Genomes Project and compared the results with those
from Pindel, BreakDancer, DELLY, Gustaf and MID. A better performance of
SRinversion was achieved for both datasets for the detection of small inversions.
AVAILABILITY AND IMPLEMENTATION: SRinversion is implemented in Perl and is
publicly available at http://paed.hku.hk/genome/software/SRinversion/index.html
CONTACT: yangwl@hku.hkSupplementary information: Supplementary data are available
at Bioinformatics online.
PMID- 27503228
TI - PRODIGY: a web server for predicting the binding affinity of protein-protein
complexes.
AB - : Gaining insights into the structural determinants of protein-protein
interactions holds the key for a deeper understanding of biological functions,
diseases and development of therapeutics. An important aspect of this is the
ability to accurately predict the binding strength for a given protein-protein
complex. Here we present PROtein binDIng enerGY prediction (PRODIGY), a web
server to predict the binding affinity of protein-protein complexes from their 3D
structure. The PRODIGY server implements our simple but highly effective
predictive model based on intermolecular contacts and properties derived from non
interface surface. AVAILABILITY AND IMPLEMENTATION: PRODIGY is freely available
at: http://milou.science.uu.nl/services/PRODIGY CONTACT: a.m.j.j.bonvin@uu.nl,
a.vangone@uu.nl.
PMID- 27503229
TI - Kinematics of anterior cruciate ligament-deficient knees in a Chinese population
during stair ascent.
AB - BACKGROUND: The purpose of this study was to measure the tibiofemoral kinematics
of anterior cruciate ligament (ACL) deficiency in a Chinese population and
compare the kinematics with published data about a Caucasian population. METHODS:
Unilateral knees of 18 Chinese ACL-deficient (ACL-D) subjects were studied while
subjects ascended stairs. Kinematic alteration was compared between ACL-D knees
and contralateral ACL-intact (ACL-I) knees. The kinematic alteration of ACL
deficiency was also compared between the Chinese population and published data
about a Caucasian population. RESULTS: A statistical difference was found in the
three-dimensional rotations between ACL-D and ACL-I knees. In the sagittal plane,
ACL-I knees had a larger flexion angle than ACL-D knees during 40 to 50 % of the
activity during stair ascent (P < 0.027) and throughout the gait cycle. A
significant difference in rotational motion between ACL-D and ACL-I knees was
also observed in the frontal plane during 40 to 60 % (P < 0.017) of the activity
and in the transverse plane during 70 to 80 % (P < 0.028) of the activity. A
greater tibial varus was demonstrated in the Chinese population while the
published data revealed external tibial rotation and a statistical difference in
translation in the Caucasian population. CONCLUSIONS: ACL-D knees show different
kinematics than ACL-I knees in the Chinese population. ACL-I knees had a larger
flexion angle than ACL-D knees in the middle stage of the activity during stair
ascent. A significant difference in rotational motion between ACL-D and ACL-I
knees was also observed in the frontal plane during the middle phase and in the
transverse plane during the terminal phase of the activity. A greater tibial
varus was demonstrated in the Caucasian population while the published data
revealed external tibial rotation and a statistical difference in translation in
the Caucasian population.
PMID- 27503231
TI - Community-acquired pneumonia in children: what to do when there is no response to
standard empirical treatment?
PMID- 27503230
TI - Traditional and HIV-specific risk factors for cardiovascular morbidity and
mortality among HIV-infected adults in Brazil: a retrospective cohort study.
AB - BACKGROUND: Antiretroviral therapy (ART) agents potentially associated with
adverse metabolic profiles are commonly used in low- and middle-income countries.
We assessed risk factors for cardiovascular disease (CVD)-related morbidity and
mortality in a cohort of HIV-infected, ART-treated adults in Rio de Janeiro,
Brazil. METHODS: Hospital records and mortality data between 2000-2010 were
examined for incident CVD-related ICD-10 and Coding of Death in HIV diagnoses
among adults >=18 years old on ART, enrolled in an observational cohort. Poisson
regression models assessed associations between demographic and clinical
characteristics and ART agent or class on CVD event risk. RESULTS: Of 2960
eligible persons, 109 had a CVD event (89 hospitalizations, 20 deaths).
Participants were 65 % male, 54 % white, and had median age of 37 and 4.6 years
on ART. The median nadir CD4(+) T lymphocyte count was 149 cells/mm(3). The
virologic suppression rate at the end of study follow-up was 60 %. In
multivariable models, detectable HIV-1 RNA prior to the event, prior CVD, less
time on ART, age >=40 at study baseline, nadir CD4(+) T lymphocyte count <=50
cells/mm(3), non-white race, male gender, and a history of hypertension were
significantly associated with CVD event incidence (p < 0.05), in order of
decreasing strength. In multivariate models, cumulative use of tenofovir,
zidovudine, efavirenz and ritonavir-boosted atazanavir, darunavir and/or
lopinavir were associated with decreased CVD event risk. Recent tenofovir and
boosted atazanavir use were associated with decreased risk, while recent
stavudine, nevirapine and unboosted nelfinavir and/or indinavir use were
associated with increased CVD event risk. CONCLUSIONS: Virologic suppression and
preservation of CD4(+) T-lymphocyte counts were as important as traditional CVD
risk factor burden in determining incident CVD event risk, emphasizing the
overall benefit of ART on CVD risk and the need for metabolically-neutral first-
and second-line ART in resource-limited settings.
PMID- 27503232
TI - The obstructive sleep apnoea syndrome in adolescents.
AB - BACKGROUND: The obstructive sleep apnoea syndrome (OSAS) results from a
combination of structural and neuromotor factors; however, the relative
contributions of these factors have not been studied during the important
developmental phase of adolescence. We hypothesised that adenotonsillar volume
(ATV), nasopharyngeal airway volume (NPAV), upper airway critical closing
pressure (Pcrit) in the hypotonic and activated neuromotor states, upper airway
electromyographic response to subatmospheric pressure and the ventilatory
response to CO2 during sleep would be major predictors of OSAS risk. METHODS: 42
obese adolescents with OSAS and 37 weight-matched controls underwent upper airway
MRI, measurements of Pcrit, genioglossal electromyography and ventilatory
response to CO2 during wakefulness and sleep. RESULTS: ATV, NPAV, activated and
hypotonic Pcrit, genioglossal electromyography and ventilatory response to CO2
during sleep were all associated with OSAS risk. Multivariate models adjusted for
age, gender, body mass index and race indicated that ATV, NPAV and activated
Pcrit each independently affected apnoea risk in adolescents; genioglossal
electromyography was independently associated in a reduced sample. There was
significant interaction between NPAV and activated Pcrit (p=0.021), with
activated Pcrit more strongly associated with OSAS in adolescents with larger
NPAVs and NPAV more strongly associated with OSAS in adolescents with more
negative activated closing pressure. CONCLUSIONS: OSAS in adolescents is mediated
by a combination of anatomic (ATV, NPAV) and neuromotor factors (activated
Pcrit). This may have important implications for the management of OSAS in
adolescents.
PMID- 27503233
TI - FUT2 genotype influences lung function, exacerbation frequency and airway
microbiota in non-CF bronchiectasis.
AB - OBJECTIVE: To assess whether FUT2 (secretor) genotype affects disease severity
and airway infection in patients with non-cystic fibrosis bronchiectasis.
PARTICIPANTS: Induced sputum samples were obtained from 112 adult patients with
high-resolution CT scan-proven bronchiectasis and at least two exacerbations in
the previous year, as part of an unrelated randomised control trial. OUTCOME
MEASURES: Presence of null FUT2 polymorphisms were determined by gene sequencing
and verified by endobronchial biopsy histochemical staining. Outcome measures
were FEV1% predicted, exacerbation frequency, and bacterial, fungal and viral
components of the microbiota (measured by culture independent approaches).
RESULTS: Patients were grouped by FUT2 loss-of-function genotype; categorised as
non-secretors (n=27, sese), heterozygous secretors (n=54, Sese) or homozygous
secretors (n=31, SeSe). FEV1% was significantly lower in SeSe patients compared
with sese patients (mean 61.6 (SD 20.0) vs 74.5 (18.0); p=0.023). Exacerbation
frequency was significantly higher in SeSe (mean count 5.77) compared with sese
(4.07; p=0.004) and Sese (4.63; p=0.026) genotypes. The time until first
exacerbation was significantly shorter in SeSe compared with Sese (HR=0.571 (95%
CI 0.343 to 0.950); p=0.031), with a similar trend for sese patients (HR=0.577
(0.311 to 1.07); p=0.081). sese had a significantly reduced frequency of
Pseudomonas aeruginosa-dominated airway infection (8.7%) compared with Sese (31%;
p=0.042) and SeSe (36%; p=0.035). In contrast, fungal, viral and non-dominant
bacterial components of the microbiome were not significantly different between
FUT2 genotypes. CONCLUSIONS: FUT2 genotype in patients with non-cystic fibrosis
bronchiectasis was significantly associated with disease outcomes, with
homozygous secretors exhibiting lower lung function, higher exacerbation number
and a higher frequency of P. aeruginosa-dominated infection. TRIAL REGISTRATION
NUMBER: ACTRN12609000578202 (anzctr.org.au); Pre-results.
PMID- 27503234
TI - Assessment of a rapid liquid-based cytology method for measuring sputum cell
counts.
AB - Differential sputum cell counting is not widely available despite proven clinical
utility in the management of asthma. We compared eosinophil counts obtained using
liquid-based cytology (LBC), a routine histopathological processing method, and
the current standard method. Eosinophil counts obtained using LBC were a strong
predictor of sputum eosinophilia (>=3%) determined by the standard method
suggesting LBC could be used in the management of asthma.
PMID- 27503235
TI - The iLappSurgery taTME app: a modern adjunct to the teaching of surgical
techniques.
AB - Application-based technology has emerged as a method of modern information
communication, and this has been applied towards surgical training and education.
It allows surgeons the ability to obtain portable and instant access to
information that is otherwise difficult to deliver. The iLappSurgery Foundation
has recently launched the transanal total mesorectal excision educational
application (taTME app) which provides a useful adjunct, especially for surgeons
interested in mastery of the taTME technique and its principles. The article
provides a detailed review of the application, which has achieved a large user
base since its debut in June, 2016.
PMID- 27503236
TI - Prostaglandin D2 receptor antagonism: a novel therapeutic option for eosinophilic
asthma?
PMID- 27503237
TI - Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with
persistent eosinophilic asthma: a single-centre, randomised, double-blind,
parallel-group, placebo-controlled trial.
AB - BACKGROUND: Eosinophilic airway inflammation is often present in asthma, and
reduction of such inflammation results in improved clinical outcomes. We
hypothesised that fevipiprant (QAW039), an antagonist of prostaglandin D2
receptor 2, might reduce eosinophilic airway inflammation in patients with
moderate-to-severe eosinophilic asthma. METHODS: We performed a single-centre,
randomised, double-blind, parallel-group, placebo-controlled trial at Glenfield
Hospital (Leicester, UK). We recruited patients with persistent, moderate-to
severe asthma and an elevated sputum eosinophil count (>=2%). After a 2-week
single-blind placebo run-in period, patients were randomly assigned (1:1) by the
trial pharmacist, using previously generated treatment allocation cards, to
receive fevipiprant (225 mg twice per day orally) or placebo, stratified by the
use of oral corticosteroid treatment and bronchoscopy. The 12-week treatment
period was followed by a 6-week single-blind placebo washout period. The primary
outcome was the change in sputum eosinophil percentage from baseline to 12 weeks
after treatment, analysed in the intention-to-treat population. All patients who
received at least one dose of study drug were included in the safety analyses.
This trial is registered with ClinicalTrials.gov, number NCT01545726, and with
EudraCT, number 2011-004966-13. FINDINGS: Between Feb 10, 2012, and Jan 30, 2013,
61 patients were randomly assigned to receive fevipiprant (n=30) or placebo
(n=31). Three patients in the fevipiprant group and four patients in the placebo
group withdrew because of asthma exacerbations. Two patients in the fevipiprant
group were incorrectly given placebo (one at the mid-treatment visit and one
throughout the course of the study). They were both included in the fevipiprant
group for the primary analysis, but the patient who was incorrectly given placebo
throughout was included in the placebo group for the safety analyses. Between
baseline and 12 weeks after treatment, sputum eosinophil percentage decreased
from a geometric mean of 5.4% (95% CI 3.1-9.6) to 1.1% (0.7-1.9) in the
fevipiprant group and from 4.6% (2.5-8.7) to 3.9% (CI 2.3-6.7) in the placebo
group. Compared with baseline, mean sputum eosinophil percentage was reduced by
4.5 times in the fevipiprant group and by 1.3 times in the placebo group
(difference between groups 3.5 times, 95% CI 1.7-7.0; p=0.0014). Fevipiprant had
a favourable safety profile, with no deaths or serious adverse events reported.
No patient withdrawals were judged by the investigator to be related to the study
drug. INTERPRETATION: Fevipiprant reduces eosinophilic airway inflammation and is
well tolerated in patients with persistent moderate-to-severe asthma and raised
sputum eosinophil counts despite inhaled corticosteroid treatment. FUNDING:
Novartis Pharmaceuticals, AirPROM project, and the UK National Institute for
Health Research.
PMID- 27503238
TI - Disseminated necrotizing leukoencephalopathy eight months after alemtuzumab
treatment for multiple sclerosis.
PMID- 27503240
TI - Genetic and phylogenetic analysis of a novel parvovirus isolated from chickens in
Guangxi, China.
AB - A previously unidentified chicken parvovirus (ChPV) strain, associated with
runting-stunting syndrome (RSS), is now endemic among chickens in China. To
explore the genetic diversity of ChPV strains, we determined the first complete
genome sequence of a novel ChPV isolate (GX-CH-PV-7) identified in chickens in
Guang Xi, China, and showed moderate genome sequence similarity to reference
strains. Analysis showed that the viral genome sequence is 86.4 %-93.9 %
identical to those of other ChPVs. Genetic and phylogenetic analyses showed that
this newly emergent GX-CH-PV-7 is closely related to Gallus gallus enteric
parvovirus isolate ChPV 798 from the USA, indicating that they may share a common
ancestor. The complete DNA sequence is 4612 bp long with an A+T content of 56.66
%. We determined the first complete genome sequence of a previously unidentified
ChPV strain to elucidate its origin and evolutionary status.
PMID- 27503239
TI - MATSAP: An automated analysis of stretch-attend posture in rodent behavioral
experiments.
AB - Stretch-attend posture (SAP) occurs during risk assessment and is prevalent in
common rodent behavioral tests. Measuring this behavior can enhance behavioral
tests. For example, stretch-attend posture is a more sensitive measure of the
effects of anxiolytics than traditional spatiotemporal indices. However,
quantifying stretch-attend posture using human observers is time consuming,
somewhat subjective, and prone to errors. We have developed MATLAB-based
software, MATSAP, which is a quick, consistent, and open source program that
provides objective automated analysis of stretch-attend posture in rodent
behavioral experiments. Unlike human observers, MATSAP is not susceptible to
fatigue or subjectivity. We assessed MATSAP performance with videos of male Swiss
mice moving in an open field box and in an elevated plus maze. MATSAP reliably
detected stretch-attend posture on par with human observers. This freely
available program can be broadly used by biologists and psychologists to
accelerate neurological, pharmacological, and behavioral studies.
PMID- 27503242
TI - Exploring the link between organizational climate and the use of psychotropic
medicines in nursing homes: A qualitative study.
AB - BACKGROUND: Research concerning the overprescribing of psychotropic medicines in
nursing homes suggests that organizational climate plays a significant role in
the use of psychotropic medicines. Organizational climate refers to how members
of the organization perceive their work environment as well as interactions with
each other or outsiders. OBJECTIVES: This study aimed to explore the key
dimensions of organizational climate and their subsequent influence on the use of
psychotropic medicines. METHODS: Semi-structured interviews were conducted with
40 on-site and visiting staff from eight nursing homes in Sydney, Australia.
Purposive sampling was used to recruit participants representing a broad range of
health disciplines and roles. Transcripts were content coded for participants'
perceptions related to the work environment and descriptions of psychotropic
medicines use. Thematic analysis was used to derive key concepts. RESULTS: Three
salient dimensions of organizational climate were linked to the use of
psychotropic medicines in nursing homes: staffing, managerial expectations and
teamwork among visiting and on-site staff. Inadequate staffing levels were
perceived to influence on-site staff requests for initiation of psychotropic
medicines to cope with high workload. Participants reported managers that
prioritized the non-pharmacological management of behavioral disturbances led
other on-site staff to have a reduced preference for psychotropic medicines. In
addition, trust and open communication among on-site and visiting staff
facilitated the cessation of psychotropic medicines. CONCLUSION: This study
illustrates that organizational climate is an important factor influencing the
use of psychotropic medicines. Furthermore, the study highlights what aspects of
organizational climate need to be addressed to reduce the inappropriate
prescribing of psychotropic medicines.
PMID- 27503241
TI - A novel role for beta2-microglobulin: a precursor of antibacterial chemokine in
respiratory epithelial cells.
AB - We analyzed a panel of cationic molecules secreted in the culture medium of human
respiratory epithelial cells (REC) upon activation by IL-1beta and different
pathogen-associated molecular patterns. A 9 kDa fragment derived from beta2
microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary
structure of sB2M-9 was revealed to increase its pI value that potentially could
play an important role in innate defense. sB2M-9 exhibits antibacterial activity
against Gram positive Staphylococcus aureus (SA) but not against Gram negative
Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a
phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA
clumps was significantly greater than that to SA without clumps. sB2M-9 binds to
SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we
demonstrated that REC release a novel chemokine with antibacterial activity that
is shed from B2M to facilitate THP-1 migration.
PMID- 27503243
TI - There is still a case for a generic qualitative approach in some pharmacy
practice research.
PMID- 27503245
TI - An inflammatory fascination for thrombosis.
PMID- 27503244
TI - The role of antagonists of the PD-1:PD-L1/PD-L2 axis in head and neck cancer
treatment.
AB - We review the current clinical knowledge surrounding one of the most promising
immune checkpoint pathways currently investigated in head and neck squamous cell
carcinoma patients, programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD
L2). We review ongoing clinical trials and associated clinical responses observed
with targeting the receptor, PD-1, and its ligand, PD-L1. A recent phase III
clinical trial (Checkmate 141) demonstrated an improved overall survival in head
and neck cancer patients treated with anti-PD-1 monotherapy as compared to
standard of care for recurrent and/or metastatic disease, which raises questions
on how best to incorporate immunotherapy in the context of standard of care. We
discuss biomarkers of response to this class of novel drugs, which is an area of
active investigation. Lastly, we project future directions in the field wherein
understanding how the Fc portions of the various monoclonal antibodies may impact
their clinical efficacy as well as discuss areas where our next advances may take
place, such as combination strategies.
PMID- 27503246
TI - FleQ of Pseudomonas putida KT2440 is a multimeric cyclic diguanylate binding
protein that differentially regulates expression of biofilm matrix components.
AB - The intracellular signal molecule cyclic di-GMP (c-di-GMP) is an important
element in regulation of biofilm formation by bacteria. In Pseudomonas
aeruginosa, FleQ functions as a c-di-GMP-dependent transcriptional regulator of
expression of flagellar genes and the exopolysaccharide (EPS) Pel, a component of
the biofilm extracellular matrix. In the plant-beneficial bacterium Pseudomonas
putida KT2440, a mutation in fleQ reduces biofilm formation and colonization of
plant surfaces. Using isothermal titration calorimetry and electrophoretic
mobility shift assays, we show in this work that FleQ of P. putida interacts with
c-di-GMP and directly binds the promoter regions of flagellar and EPS genes. Data
obtained by analytical gel filtration and ultracentrifugation indicate that FleQ
is in multiple oligomeric states in solution (dimers, tetramers and hexamers),
which do not show altered equilibrium in the presence of c-di-GMP. DNA binding is
independent of c-diGMP, although it is favored by the second messenger in the
case of the promoter of the operon responsible for synthesis of the species
specific EPS Pea. Analysis of expression using transcriptional fusions showed an
influence of FleQ upon two of the four EPS operons under regular growth
conditions. Finally, a consensus sequence for promoter recognition by FleQ in P.
putida is also proposed.
PMID- 27503247
TI - Use of dermal regeneration template to close a giant myelomeningocele in a
newborn.
AB - Many techniques are available to close a myelomeningocele, but large lesions can
be particularly difficult to close given the absence of surrounding tissue. The
authors present the case of a 2-day-old girl with a large lumbosacral
myelomeningocele who underwent a staged repair using dermal regeneration template
(DRT; Integra) followed by split-thickness skin grafting. The results
demonstrated that the combined use of myofascial turnover flaps and DRT with
delayed skin grafting is a safe, effective option for this challenging
reconstructive dilemma.
PMID- 27503248
TI - Timing of cranial vault remodeling in nonsyndromic craniosynostosis: a single
institution 30-year experience.
AB - OBJECTIVE Due to the changing properties of the infant skull, there is still no
clear consensus on the ideal time to surgically intervene in cases of
nonsyndromic craniosynostosis (NSC). This study aims to shed light on how patient
age at the time of surgery may affect surgical outcomes and the subsequent need
for reoperation. METHODS A retrospective cohort review was conducted for patients
with NSC who underwent primary cranial vault remodeling between 1990 and 2013.
Patients' demographic and clinical characteristics and surgical interventions
were recorded. Postoperative outcomes were assessed by assigning each procedure
to a Whitaker category. Multivariate logistic regression analysis was performed
to determine the relationship between age at surgery and need for minor (Whitaker
I or II) versus major (Whitaker III or IV) reoperation. Odds ratios (ORs) for
Whitaker category by age at surgery were assigned. RESULTS A total of 413 unique
patients underwent cranial vault remodeling procedures for NSC during the study
period. Multivariate logistic regression demonstrated increased odds of requiring
major surgical revisions (Whitaker III or IV) in patients younger than 6 months
of age (OR 2.49, 95% CI 1.05-5.93), and increased odds of requiring minimal
surgical revisions (Whitaker I or II) in patients older than 6 months of age (OR
2.72, 95% CI 1.16-6.41). CONCLUSIONS Timing, as a proxy for the changing
properties of the infant skull, is an important factor to consider when planning
vault reconstruction in NSC. The data presented in this study demonstrate that
patients operated on before 6 months of age had increased odds of requiring major
surgical revisions.
PMID- 27503250
TI - [Not Available].
PMID- 27503249
TI - Randomized Pharmacokinetic Crossover Study Comparing 2 Curcumin Preparations in
Plasma and Rectal Tissue of Healthy Human Volunteers.
AB - Curcumin is poorly absorbed, which is interest in new preparations. However,
little is known about variations in its pharmacokinetics and tissue
bioavailability between formulations. In this randomized, crossover study we
evaluated the relationship between steady-state plasma and rectal tissue
curcuminoid concentrations using standard and phosphatidylcholine curcumin
extracts. There was no difference in the geometric mean plasma AUCs when adjusted
for the 10-fold difference in curcumin dose between the 2 formulations.
Phosphatidylcholine curcumin extract yielded only 20% to 30% plasma
demethoxycurcumin and bisdemethoxycurcumin conjugates compared to standard
extract, yet yielded 20-fold greater hexahydrocurcumin. When adjusting for
curcumin dose, tissue curcumin concentrations were 5-fold greater for the
phosphatidylcholine extract. Improvements in curcuminoid absorption due to
phosphatidylcholine are not uniform across the curcuminoids. Furthermore,
curcuminoid exposures in the intestinal mucosa are most likely due to luminal
exposure rather than to plasma disposition. Finally, once-daily dosing is
sufficient to maintain detectable curcuminoids at steady state in both plasma and
rectal tissues.
PMID- 27503251
TI - [IgG4-related disease].
PMID- 27503252
TI - Effects of cranial integration on hominid endocranial shape.
AB - Because brains do not fossilize, the internal surface of the braincase (endocast)
serves as an important source of information about brain growth, development, and
evolution. Recent studies of endocranial morphology and development in great
apes, fossil hominins, and modern humans have revealed taxon-specific
differences. However, it remains to be investigated to which extent differences
in endocranial morphology reflect differences in actual brain morphology and
development, and to which extent they reflect different interactions of the brain
and its case with the cranial base and face. Here we address this question by
analyzing the effects of cranial integration on endocranial morphology. We test
the 'spatial packing' and 'facial orientation' hypotheses, which propose that
size and orientation of the neurocranium relative to the viscerocranium influence
endocranial shape. Results show that a substantial proportion of endocranial
shape variation along and across ontogenetic trajectories is due to cranial
integration. Specifically, the uniquely globular shape of the human endocast
mainly results from the combination of an exceptionally large brain with a
comparatively small face. Overall, thus, cranial integration has pervasive
effects on endocranial morphology, and only a comparatively small proportion of
inter- and intra-taxon variation can directly be associated with variation in
brain morphology.
PMID- 27503253
TI - Bibliometric analysis on global Behcet disease publications during 1980-2014: is
there a Silk Road in the literature?
AB - BACKGROUND: Behcet disease (BD) is a chronic and multisystemic vasculitis
characterized with recurrent oral and genital ulcers, uveitis, arthritis and skin
manifestations. The highest prevalence of the disease has been reported in
regions historically involved in the Silk Road routes. OBJECTIVE: We aimed to
analyse Behcet literature and evaluate whether there is a concordance between
ancient Silk Road regions and the distribution of publication productivity.
METHODS: The bibliometric analysis of the publications published during 1980-2014
using Thomson Reuters Web of Science database was performed. We generated
infographics of productivity and also analysed the correlations among economical
productivities, technological advancement levels and humanity index and
productivity performances of 78 countries in Behcet literature. RESULTS: Turkey
ranked first in Behcet literature with 1837 articles followed by Japan and the
USA. Turkey, Tunisia and Israel occupied the first three places in productivity.
Significant correlations were noted between 2014 gross economic and technological
indices and publication numbers of the countries. We found that European
countries had high productivity, although they had low prevalence of BD. We
detected no concordance between the productivity density of the countries and the
ancient Silk Road routes. CONCLUSION: Most publications were reported from
developed countries although undeveloped or developing countries had higher
prevalence of BD. Physicians in undeveloped and developing countries should be
supported and encouraged to perform novel studies on BD.
PMID- 27503254
TI - Stabilization of Charge Carriers in Picket-Fence Polythiophenes Using Dielectric
Side Chains.
AB - Insulated molecular wires (IMWs) are pi-conjugated polymers that are molecularly
sheathed with an insulating layer and are structurally analogous to electric
power cords at the nanoscale. Such unique architectures are expected in molecular
electronics and organic devices. Herein, we propose a new molecular design
concept of IMWs, in which the sheaths can be customized, thereby enabling the
modulation of the electronic properties of the interior pi-conjugated systems. To
this end, we focused our attention on the dielectric constant of the sheaths, as
it governs the electrostatic interaction between charges. Upon doping, charge
carriers, such as polaron and bipolaron, were generated regardless of the
dielectric properties of the sheaths. Flash-photolysis time-resolved microwave
conductivity measurements revealed that intrawire charge carrier mobility was
independent of the sheaths. However, we found that the charge carriers could be
stabilized by the sheaths with a high dielectric constant owing to the charge
screening effect. We expect that IMWs designed in this way will be useful in a
variety of applications, where the nature of charge carriers plays an important
role, and particularly when redox switching is required (e.g., electrochromic,
magnetic, and memory applications).
PMID- 27503256
TI - Cu0.89Zn0.11O, A New Peroxidase-Mimicking Nanozyme with High Sensitivity for
Glucose and Antioxidant Detection.
AB - Nanomaterial-based enzyme mimetics (nanozymes) is an emerging field of research
that promises to produce alternatives to natural enzymes for a variety of
applications. The search for the most cost-effective and efficient inorganic
nanomaterials, such as metal oxides, cannot be won by pristine CuO. However,
unlike CuO, the Zn-doped CuO (Zn-CuO) nanoparticles reported in this paper reveal
superior peroxidase-like enzyme activity. This places Zn-CuO in a good position
to participate in a range of activities aimed at developing diverse enzyme
applications. The peroxidase-like activity was tested and confirmed against
various chromogenic substrates in the presence of H2O2 and obeyed the Michaelis
Menten enzymatic pathway. The mechanism of enhanced enzymatic activity was proved
by employing terephthalic acid as a fluorescence probe and by electron spin
resonance. The nanozyme, when tested for the detection of glucose, showed a
substantial enhancement in the detection selectivity. The limit of detection
(LOD) was also decreased reaching a limit as low as 0.27 ppm. Such a low LOD has
not been reported so far for the metal oxides without any surface modifications.
Moreover, the nanozyme (Zn-CuO) was utilized to detect the three antioxidants
tannic acid, tartaric acid, and ascorbic acid and the relative strength of their
antioxidant capacity was compared.
PMID- 27503257
TI - Chickpea Ferritin CaFer1 Participates in Oxidative Stress Response, and Promotes
Growth and Development.
AB - Ferritins store and sequester iron, and regulate iron homeostasis. The cDNA for a
stress-responsive phytoferritin, previously identified in the extracellular
matrix (ECM) of chickpea (Cicer arietinum), was cloned and designated CaFer1. The
CaFer1 transcript was strongly induced in chickpea exposed to dehydration,
hypersalinity and ABA treatment. Additionally, it has role in the defense against
Fusarium oxysporum infection. Functional complementation of the yeast frataxin
deficient mutant, Deltayfh1, indicates that CaFer1 functions in oxidative stress.
The presence of CaFer1 in the extracellular space besides chloroplast establishes
its inimitable nature from that of other phytoferritins. Furthermore, CaFer1
expression in response to iron suggests its differential mechanism of
accumulation at two different iron conditions. CaFer1-overexpressing transgenic
plants conferred improved growth and development, accompanied by altered
expression of iron-responsive genes. Together, these results suggest that the
phytoferritin, CaFer1, might play a key role in maintenance of iron buffering and
adaptation to environmental challenges.
PMID- 27503258
TI - Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine
needle aspiration biopsy: a case report.
AB - Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of
eosinophilic infiltration into the squamous epithelium. In contrast, another
disease concept termed "eosinophilic esophageal myositis (EoEM)" has been
proposed, whereby there is eosinophilic infiltration into the muscularis propria
instead. A 60-year-old man was referred to our hospital for chest pain,
dysphagia, and several episodes of esophageal food impaction. Although EoE was
suspected based on clinical features, biopsy specimens showed no mucosal
eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the
muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy
(EUS-FNA) revealed eosinophilic infiltration into the muscularis propria.
Although the patient's symptoms gradually improved after steroid administration,
complete remission was not achieved after 1 year of treatment. This case may
reflect a disorder distinct from typical EoE based on eosinophilic infiltration
of the muscularis propria but not the squamous epithelium, and we, therefore,
diagnosed it as EoEM using the EUS-FNA findings as reference.
PMID- 27503260
TI - Mesocrystals: structural and morphogenetic aspects.
AB - Mesocrystals are a fascinating class of crystalline nanostructured materials
since they combine the properties of nanoparticles with order on the microscopic
or even macroscopic length scale. This tutorial review deals with the structural
aspects of mesocrystals as well as their formation mechanisms known so far. The
goal is to reach an understanding about what is special about the structuration
principles of mesocrystals and their complex structures and what are the
possibilities to control their formation processes.
PMID- 27503259
TI - Computational characterization of Iron metabolism in the Tsetse disease vector,
Glossina morsitans: IRE stem-loops.
AB - BACKGROUND: Iron metabolism and regulation is an indispensable part of species
survival, most importantly for blood feeding insects. Iron regulatory proteins
are central regulators of iron homeostasis, whose binding to iron response
element (IRE) stem-loop structures within the UTRs of genes regulate expression
at the post-transcriptional level. Despite the extensive literature on the
mechanism of iron regulation in human, less attention has been given to insect
and more specifically the blood feeding insects, where research has mainly
focused on the characterization of ferritin and transferrin. We thus, examined
the mechanism of iron homeostasis through a genome-wide computational
identification of IREs and other enriched motifs in the UTRs of Glossina
morsitans with the view to identify new IRE-regulated genes. RESULTS: We
identified 150 genes, of which two are known to contain IREs, namely the ferritin
heavy chain and the MRCK-alpha. The remainder of the identified genes is
considered novel including 20 hypothetical proteins, for which an iron-regulatory
mechanism of action was inferred. Forty-three genes were found with IRE
signatures of regulation in two or more insects, while 46 were only found to be
IRE-regulated in two species. Notably 39 % of the identified genes exclusively
shared IRE-signatures in other Glossina species, which are potentially Glossina
specific adaptive measures in addressing its unique reproductive biology and
blood meal-induced iron overload. In line with previous findings, we found no
evidence pertaining to an IRE regulation of Transferrin, which highlight the
importance of ferritin heavy chain and the other proposed transporters in the
tsetse fly. In the context of iron-sequestration, key players of tsetse immune
defence against trypanosomes have been introduced namely 14 stress and immune
response genes, while 28 cell-envelop, transport, and binding genes were assigned
a putative role in iron trafficking. Additionally, we identified and annotated
enriched motifs in the UTRs of the putative IRE-regulated genes to derive at a co
regulatory network that maintains iron homeostasis in tsetse flies. Three
putative microRNA-binding sites namely Gy-box, Brd-box and K-box motifs were
identified among the regulatory motifs, enriched in the UTRs of the putative IRE
regulated genes. CONCLUSION: Beyond our current view of iron metabolism in
insects, with ferritin and transferrin as its key players, this study provides a
comprehensive catalogue of genes with possible roles in the acquisition;
transport and storage of iron hence iron homeostasis in the tsetse fly.
PMID- 27503255
TI - A protein-truncating R179X variant in RNF186 confers protection against
ulcerative colitis.
AB - Protein-truncating variants protective against human disease provide in vivo
validation of therapeutic targets. Here we used targeted sequencing to conduct a
search for protein-truncating variants conferring protection against inflammatory
bowel disease exploiting knowledge of common variants associated with the same
disease. Through replication genotyping and imputation we found that a predicted
protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative
colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon
ring finger E3 ligase with strong colonic expression, protects against ulcerative
colitis (overall P=6.89 * 10(-7), odds ratio=0.30). We further demonstrate that
the truncated protein exhibits reduced expression and altered subcellular
localization, suggesting the protective mechanism may reside in the loss of an
interaction or function via mislocalization and/or loss of an essential
transmembrane domain.
PMID- 27503261
TI - WHO medical eligibility criteria update.
PMID- 27503262
TI - Risk-benefit analysis of navigation techniques for vertebral transpedicular
instrumentation: a prospective study.
AB - BACKGROUND CONTEXT: Pedicle screws in spinal surgery have allowed greater
biomechanical stability and higher fusion rates. However, malposition is very
common and may cause neurologic, vascular, and visceral injuries and compromise
mechanical stability. PURPOSE: The purpose of this study was to compare the
malposition rate between intraoperative computed tomography (CT) scan assisted
navigation and free-hand fluoroscopy-guided techniques for placement of pedicle
screw instrumentation. STUDY DESIGN/SETTING: This is a prospective, randomized,
observational study. PATIENT SAMPLE: A total of 114 patients were included: 58 in
the assisted surgery group and 56 in the free-hand fluoroscopy-guided surgery
group. OUTCOME MEASURES: Analysis of screw position was assessed using the Heary
classification. Breach severity was defined according to the Gertzbein
classification. Radiation doses were evaluated using thermoluminescent
dosimeters, and estimates of effective and organ doses were made based on scan
technical parameters. METHODS: Consecutive patients with degenerative disease,
who underwent surgical procedures using the free-hand, or intraoperative
navigation technique for placement of transpedicular instrumentation, were
included in the study. RESULTS: Forty-four out of 625 implanted screws were
malpositioned: 11 (3.6%) in the navigated surgery group and 33 (10.3%) in the
free-hand group (p<.001). Screw position according to the Heary scale was Grade
II (4 navigated surgery, 6 fluoroscopy guided), Grade III (3 navigated surgery,
11 fluoroscopy guided), Grade IV (4 navigated surgery, 16 fluoroscopy guided),
and Grade V (1 fluoroscopy guided). There was only one symptomatic case in the
conventional surgery group. Breach severity was seven Grade A and four Grade B in
the navigated surgery group, and eight Grade A, 24 Grade B, and one Grade C in
free-hand fluoroscopy-guided surgery group. Radiation received per patient was
5.8 mSv (4.8-7.3). The median dose received in the free-hand fluoroscopy group
was 1 mGy (0.8-1.1). There was no detectable radiation level in the navigation
assisted surgery group, whereas the effective dose was 10 uGy in the free-hand
fluoroscopy-guided surgery group. CONCLUSIONS: Malposition rate, both symptomatic
and asymptomatic, in spinal surgery is reduced when using CT-guided placement of
transpedicular instrumentation compared with placement under fluoroscopic
guidance, with radiation values within the safety limits for health. Larger
studies are needed to determine risk-benefit in these patients.
PMID- 27503263
TI - Transient physical and psychosocial activities increase the risk of nonpersistent
and persistent low back pain: a case-crossover study with 12 months follow-up.
AB - BACKGROUND CONTEXT: A previous study has shown that transient physical and
psychosocial activities increased the risk of developing low back pain. However,
the link between these factors in triggering nonpersistent or persistent episodes
remains unclear. PURPOSE: We aimed to investigate the association of transient
exposures to physical and psychosocial activities with the development of
nonpersistent or persistent low back pain. STUDY DESIGN: This was a case
crossover study with 12 months follow-up. PATIENT SAMPLE: We included 999
consecutive participants seeking care for a sudden onset of low back pain.
OUTCOME MEASURES: Development of low back pain was the outcome measure. MATERIALS
AND METHODS: At baseline, participants reported transient exposures to 12
predefined activities over the 4 days preceding pain onset. After 12 months,
participants were asked whether they had recovered and the date of recovery.
Exposures in the 2-hour period preceding pain onset (case window) were compared
with the 2-hour period, 24 hours before pain onset (control window) in a case
crossover design for all participants. Conditional logistic regression was used
to calculate odds ratios (ORs) and 95% confidence intervals (CI), and interaction
analyses were used to compare estimates of nonpersistent (i.e., <6 weeks
duration) and persistent cases. This study received funding from Australia's
National Health and Medical Research Council (APP1003608). RESULTS: There were
832 participants (83%) who completed the 12 months follow-up successfully. Of
these, 430 participants had nonpersistent low back pain (<6 weeks duration),
whereas 352 reported persistent symptoms (>=6 weeks duration). Exposure to
several transient activities, such as manual tasks involving heavy loads, awkward
postures, live people or animals, moderate or vigorous physical activity, and
being fatigued or tired during a task or activity, significantly increased the
risk of both nonpersistent and persistent low back pain, with ORs ranging from
2.9 to 11.7. Overall, the risk of developing a persistent or a nonpersistent
episode of low back pain associated with the included physical factors did not
differ significantly. CONCLUSIONS: Our results revealed that previously
identified triggers contribute equally to the development of both nonpersistent
and persistent low back pain. Future prevention strategies should focus on
controlling exposure to these triggers as they have the potential to decrease the
burden associated with both acute and chronic low back pain.
PMID- 27503264
TI - Preoperative and postoperative sagittal plane analysis in adult idiopathic
scoliosis in patients older than 40 years of age.
AB - BACKGROUND CONTEXT: Most of the papers correlate sagittal radiographic parameters
with health-related quality of life (HRQOL) scores for patients with scoliosis.
However, we do not know how changes in sagittal profile influence clinical
outcomes after surgery in adult population operated for mainly frontal deformity.
PURPOSE: This study aimed to analyze spinal sagittal profile in a population
operated on adult idiopathic scoliosis (AS) and to describe variations in
sagittal parameters after surgery and the association between those variations
and clinical outcomes. DESIGN/SETTING: This is a historical cohort study. PATIENT
SAMPLE: We included in this study 40 patients operated on AS, older than 40 at
the time of surgery (mean age 54.9), and with more than 2-year follow-up (mean
7.4 years). OUTCOME MEASURES: Full-length free-standing radiographs, Scoliosis
Research Society 22 (SRS22) and Short Form 36 (SF36) instruments, and
satisfaction with outcomes were available at final follow-up. METHODS: Sagittal
preoperative and final follow-up radiographic parameters, radiographic
correlation with HRQOL scores at final follow-up, and association between
satisfaction and changes in sagittal profile were analyzed. A multivariate
analysis was performed. No funds were received for this article. RESULTS:
Preoperatively, the spinal sagittal plane tended to exhibit kyphosis. Most
sagittal parameters did not improve at final follow-up with respect to
preoperative values. We saw, after univariate analysis, that worse sagittal
profile leads to worse HRQOL, but after multivariate analysis, only spinal tilt
(ST) persisted as possible predictor for worse SRS activity scores. Frontal Cobb
significantly improved. Most patients (82%) were satisfied with final outcomes.
Variations in sagittal profile parameters did not differ between satisfied and
dissatisfied patients. CONCLUSIONS: Although most sagittal plane parameters did
not improve after surgery, surgical treatment in AS achieves a high satisfaction
rate. Good clinical results do not correlate with improving sagittal plane
parameters. Sagittal profile measurements are not helpful to decide surgical
treatment in patients with mainly frontal deformity.
PMID- 27503265
TI - The impact of generalized joint laxity (GJL) on the posterior neck pain, cervical
disc herniation, and cervical disc degeneration in the cervical spine.
AB - BACKGROUND CONTEXT: Generalized joint laxity (GJL) can have a negative impact on
lumbar spine pathology, including low back pain, disc degeneration, and disc
herniation, but the relationship between GJL and cervical spine conditions
remains unknown. PURPOSE: To investigate the relationship between GJL and
cervical spine conditions, including the prevalence of posterior neck pain (PNP),
cervical disc herniation (CDH), and cervical disc degeneration (CDD), in a young,
active population. STUDY DESIGN: Retrospective 1:2 matched cohort (case-control)
study from prospectively collected data PATIENT SAMPLE: Of a total of 1853
individuals reviewed, 73 individuals with GJL (study group, gruop A) and 146
without GJL (control group, Group B) were included in the study according to a
1:2 case-control matched design for age, sex, and body mass index. OUTCOME
MEASURE: The primary outcome measure was the prevalence and intensity of PNP at
enrollment based on a visual analogue scale score for pain. The secondary outcome
measures were (1) clinical outcomes as measured with the neck disability index
(NDI) and 12-item short form health survey (SF-12) at enrollment, and (2)
radiological outcomes of CDH and CDD at enrollment. METHODS: We compared baseline
data between groups. Descriptive statistical analyses were performed to compare
the 2 groups in terms of the outcome measures. RESULTS: The prevalence and
intensity of PNP were significantly greater in group A (patients with GJL) than
in group B (patients without GJL) (prevalence: p=.02; intensity: p=.001).
Clinical outcomes as measured with NDI and SF-12 did not differ significantly
between groups. For radiologic outcomes, the prevalence of CDD was significantly
greater in group A than in group B (p=.04), whereas the prevalence of CDH did not
differ significantly between groups (p=.91). CONCLUSIONS: The current study
revealed that GJL was closely related to the prevalence and intensity of PNP,
suggesting that GJL may be a causative factor for PNP. In addition, GJL may
contribute to the occurrence of CDD, but not CDH. Spine surgeons should screen
for GJL in patientswith PNP and inform patients of its potential negative impact
on disc degeneration of the cervical spine.
PMID- 27503266
TI - The computed tomography angiography study of the spatial relationship between C1
transpedicular screw trajectory and V3 segment of vertebral artery.
AB - BACKGROUND CONTEXT: To our knowledge, there is no study that has systematically
analyzed the relationship between C1 transpedicular screw trajectory and V3
segment of vertebral artery (VA V3 segment). PURPOSE: To study the relationship
between C1 transpedicular screw trajectory and VA V3 segment. STUDY DESIGN: A
morphologic computed tomography angiography (CTA) analysis of the spatial
relationship between C1 transpedicular screw trajectory and VA V3 segment.
METHODS: Measurements were made on a workstation by using CTA data of 62
patients. Firstly, parameters related to the relationship between C1 vertebral
artery groove (VAG) and vertebral artery (VA) were measured: (A) the shortest
distance between the posterosuperior aspect of C1 posterior arch and VA; (B)
distance between the outer aspect of VAG and VA; (C) distance between midpoint of
VAG and VA; and (D) distance between the inner aspect of the VAG and VA. Then,
the central axis of trajectory perpendicular to the coronal plane (axis P) and
the central axis of trajectory with a medial inclination (axis M) were designed
for the basis of measurements. Parameters related to the relationship between
axis P/M and VA V3 segment were measured respectively: (E, E'), distance between
insertion point and anterior aspect of VA along axis P/M; (F, F'), the shortest
distance between axis P/M and the outer cortex of C1 transverse foramen; and (G,
G'), the narrowest width of C1 internal medullary canal along axis P/M. RESULT:
A, B, C, and D were 1.7+/-1.0 mm, 1.6+/-0.9 mm, 1.5+/-0.7 mm, 2.3+/-1.1 mm,
respectively. E, E' were 5.5+/-1.7 mm and 4.1+/-2.3 mm. F, F' were 1.9+/-0.7 mm
and 2.9+/-0.7 mm. G, G' were 3.7+/-1.4 mm and 4.8+/-1.2 mm. There was a little
interspace between atlas VAG and VA, which was mainly filled with venous plexus.
CONCLUSIONS: There is a close relationship between C1 transpedicular screw
trajectory and VA V3 segment. Trajectory with medial inclination technique is
suggested especially for female patients.
PMID- 27503268
TI - Infant Strangulation from an Amber Teething Necklace.
AB - Amber teething necklaces supposedly provide analgesia for teething infants. Their
use is becoming more widespread, despite lack of peer-reviewed evidence and
warnings from Health Canada that they pose a strangulation and aspiration risk.
To date, there have been no published reports of strangulation secondary to amber
teething necklaces. In this report we present a case of non-fatal infant
strangulation from the first time use of an amber teething necklace. We will also
discuss the role of physicians as advocates in reporting similar cases and
educating families. Finally, we will comment on the responsibility of all
professionals and professional organizations that work with infants and toddlers
to advocate for children by raising concerns and counselling parents.
PMID- 27503267
TI - Prostate-specific extracellular vesicles as a novel biomarker in human prostate
cancer.
AB - Extracellular vesicles (EVs) may play an important role in cancer development and
progression. We aimed to investigate the prognostic potential of prostate
specific EVs in prostate cancer (PCa) patients. Plasma and prostate tissue were
collected from patients who underwent surgery for PCa (n = 82) or benign
prostatic hyperplasia (BPH, n = 28). To analyze the quantity of EVs in prostate,
we performed transmission electron microscopy (TEM), immuno-TEM with CD63 and
prostate-specific membrane antigen (PSMA), and immunofluorescence staining. After
EV isolation from plasma, CD63 and PSMA concentration was measured using ELISA
kits. PSMA-positive areas in prostate differed in patients with BPH, and low-,
intermediate-, and high-risk PCa (2.4, 8.2, 17.5, 26.5%, p < 0.001). Plasma PSMA
positive EV concentration differed in patients with BPH, and low-, intermediate-,
and high-risk PCa (21.9, 43.4, 49.2, 59.9 ng/mL, p < 0.001), and ROC curve
analysis indicated that plasma PSMA-positive EV concentration differentiated PCa
from BPH (AUC 0.943). Patients with lower plasma PSMA-positive EV concentration
had greater prostate volume (50.2 vs. 33.4 cc, p < 0.001) and lower pathologic
Gleason score (p = 0.025). During the median follow-up of 18 months, patients
with lower plasma PSMA-positive EV concentration tended to have a lower risk of
biochemical failure than those with higher levels of prostate-specific EVs (p =
0.085).
PMID- 27503269
TI - Drosophila glob1 is required for the maintenance of cytoskeletal integrity during
oogenesis.
AB - BACKGROUND: Hemoglobins (Hbs) are evolutionarily conserved heme-containing
metallo-proteins of the Globin protein family that harbour the characteristic
"globin fold." Hemoglobins have been functionally diversified during evolution
and their usual property of oxygen transport is rather a recent adaptation.
Drosophila genome possesses three globin genes (glob1, glob2, and glob3), and we
have reported earlier that adequate expression of glob1 is required for various
aspects of development, as well as to regulate the cellular level of reactive
oxygen species (ROS). The present study illustrates the explicit role of
Drosophila globin1 in progression of oogenesis. RESULTS: We demonstrate a dynamic
expression pattern of glob1 in somatic and germ cell derivatives of developing
egg chambers during various stages of oogenesis, which largely confines around
the F-actin-rich cellular components. Reduced expression of glob1 leads to
various types of abnormalities during oogenesis, which were primarily mediated by
the inappropriately formed F-actin-based cytoskeleton. Our subsequent analysis in
the somatic and germ line clones shows cell autonomous role of glob1 in the
maintenance of the integrity of F-actin-based cytoskeleton components in the
somatic and germ cell derivatives. CONCLUSIONS: Our study establishes a novel
role of glob1 in maintenance of F-actin-based cytoskeleton during progression of
oogenesis in Drosophila. Developmental Dynamics 245:1048-1065, 2016. (c) 2016
Wiley Periodicals, Inc.
PMID- 27503271
TI - Increased Blood Viscosity in Ischemic Stroke Patients with Small Artery Occlusion
Measured by an Electromagnetic Spinning Sphere Viscometer.
AB - BACKGROUND AND PURPOSE: High blood viscosity causes blood stagnation and
subsequent pathological thrombotic events, resulting in the development of
ischemic stroke. We hypothesize that the contribution of blood viscosity may
differ among ischemic stroke subtypes based on specific pathological conditions.
We tried to verify this hypothesis by measuring blood viscosity in acute ischemic
stroke patients using a newly developed electromagnetic spinning sphere (EMS)
viscometer. METHODS: Measurements in acute ischemic stroke patients were
performed 4 times during admission and data were compared with those obtained
from 100 healthy outpatient volunteers. RESULTS: We enrolled 92 patients
(cardioembolism: 25, large artery atherosclerosis: 42, and small artery occlusion
[SAO]: 25) in this study. Comparisons of blood viscosity between the ischemic
stroke subgroups and control group revealed that blood viscosity at the date of
admission was significantly higher in the SAO group (5.37 +/- 1.11 mPa?s) than in
the control group (4.66 +/- .72 mPa?s) (P < .01). Among all subtype groups
showing a reduction in blood viscosity after 2 weeks, the SAO group showed the
highest and most significant reduction, indicating that SAO patients had the most
concentrated blood at the onset. CONCLUSIONS: Blood viscosity was significantly
increased in the SAO group at the date of admission, which indicated the
contribution of dehydration to the onset of ischemic stroke. The importance of
dehydration needs to be emphasized more in the pathogenesis of SAO. The clinical
application of the EMS viscometer is promising for understanding and
differentiating the pathogenesis of ischemic stroke.
PMID- 27503270
TI - Composite Membranes of Recombinant Silkworm Antimicrobial Peptide and Poly (L
lactic Acid) (PLLA) for biomedical application.
AB - Antimicrobial peptides, produced by innate immune system of hosts in response to
invading pathogens, are capable of fighting against a spectrum of bacteria,
viruses, fungi, parasites and cancer cells. Here, a recombinant silkworm AMP
Bmattacin2 from heterologous expression is studied, indicating a broad spectrum
of antibacterial activity and showing selective killing ability towards skin and
colon cancer cells over their normal cell counterparts. For the purpose of
biomedical application, the electrospinning fabrication technique is employed to
load Bmattacin2 into PLLA nanofibrous membrane. In addition to a good
compatibility with the normal cells, Bmattacin2 loaded nanofibrous membranes
demonstrate instant antibacterial effects and sustained anticancer effects. The
cancer cell and bacteria targeting dynamics of recombinant Bmattacin2 are
investigated. With these characteristics, PLLA/Bmattacin2 composite membranes
have a great potential for developing novel biomedical applications such as
cancer therapies and wound healing treatments.
PMID- 27503272
TI - Can Prediction of Functional Outcome after Stroke Be Improved by Adding
Fibrinogen to Prognostic Model?
AB - BACKGROUND: Several studies demonstrated that elevated plasma fibrinogen level is
associated with poor functional outcome after ischemic stroke. It remains,
however, unclear if prediction of functional outcome after stroke can be improved
by adding fibrinogen to prognostic model. We aimed to determine the prognostic
value of plasma fibrinogen for the prediction of functional outcome after
ischemic stroke. METHODS: We retrospectively analyzed the data of 727 ischemic
stroke patients (median age: 70; 48% men). The functional outcome was assessed 1
month after stroke onset using modified Rankin Scale. Unfavorable outcome was
defined as modified Rankin Scale score higher than 2. Using C-statistic and
reclassification measures (net reclassification improvement-NRI and integrated
discrimination improvement-IDI), we compared the predictive abilities of 2
models. The first model contained stroke severity and age, and the second one
included fibrinogen in addition. RESULTS: After adjusting for age and stroke
severity, plasma fibrinogen level higher than 2.95 g/L was associated with
unfavorable outcome (OR: 1.80, 95% CI: 1.20-2.72, P < .01). The addition of
fibrinogen did not lead to an improvement in predictive ability of the model. C
statistic did not differ between models (.90 versus .90, P = .34). The
categorical NRI was .01 (P = .66) and the IDI was .006 (P = .08). CONCLUSIONS:
The addition of fibrinogen to predictive model including age and stroke severity
does not improve discrimination between favorable and unfavorable outcomes after
ischemic stroke.
PMID- 27503273
TI - Blood Pressure Is the Determinant for the Increased Risk for Intracranial
Arterial Stenosis in Subjects with Elevated Glycated Hemoglobin Levels: The
Kangbuk Samsung Health Study.
AB - BACKGROUND AND PURPOSE: Ischemic stroke is known to be an important vascular
complication of diabetes. Intracranial arterial stenosis (ICAS) is considered as
an important cause of stroke in Asians. We aimed to analyze the risk for ICAS
assessed by transcranial Doppler (TCD) ultrasonography in different groups of
young Korean subjects divided by glycated hemoglobin (HbA1c) levels. METHODS:
This study included 10,437 participants without history of cardiovascular
diseases (81.3% men, mean age 43 years) from a health screening program, in whom
TCD ultrasonography was used to detect greater than 50% ICAS based on criteria
modified from the SONIA (Stroke Outcomes and Neuroimaging of Intracranial
Atherosclerosis) trial. The subjects were divided into 3 groups according to
HbA1c levels: HbA1c < 5.7%, 5.7 <= HbA1c < 6.5%, and HbA1c >= 6.5% or under
medication for diabetes. RESULTS: Among the participants, 3.0% of the subjects
had ICAS. The subjects with ICAS tended to have higher mean HbA1c level compared
with those without ICAS (5.8 +/- .8 versus 5.7 +/- .6, P = .063). The proportion
of subjects with ICAS significantly increased as the HbA1c increased from the
first to the third group (2.8%, 3.0%, 4.6%, P for linear trend = .022). In
logistic regression analysis with ICAS as the dependent variable, the group with
HbA1c >= 6.5% showed significantly increased odds ratio for ICAS with subjects
with HbA1c < 5.7% as the reference after adjustment for confounding variables
(1.575, 95% confidence interval 1.056-2.347). However, this significance
disappeared with inclusion of presence of hypertension in the model. CONCLUSIONS:
The risk for ICAS assessed by TCD was increased in young Korean subjects with
HbA1c >= 6.5%. However, this significance was attenuated after adjustment for
presence of hypertension, suggesting the importance of hypertension in ICAS.
PMID- 27503274
TI - A hole inversion layer at the BiVO4/Bi4V2O11 interface produces a high tunable
photovoltage for water splitting.
AB - The conversion of solar energy into hydrogen fuel by splitting water into
photoelectrochemical cells (PEC) is an appealing strategy to store energy and
minimize the extensive use of fossil fuels. The key requirement for efficient
water splitting is producing a large band bending (photovoltage) at the
semiconductor to improve the separation of the photogenerated charge carriers.
Therefore, an attractive method consists in creating internal electrical fields
inside the PEC to render more favorable band bending for water splitting.
Coupling ferroelectric materials exhibiting spontaneous polarization with visible
light photoactive semiconductors can be a likely approach to getting higher
photovoltage outputs. The spontaneous electric polarization tends to promote the
desirable separation of photogenerated electron- hole pairs and can produce
photovoltages higher than that obtained from a conventional p-n heterojunction.
Herein, we demonstrate that a hole inversion layer induced by a ferroelectric
Bi4V2O11 perovskite at the n-type BiVO4 interface creates a virtual p-n junction
with high photovoltage, which is suitable for water splitting. The photovoltage
output can be boosted by changing the polarization by doping the ferroelectric
material with tungsten in order to produce the relatively large photovoltage of
1.39 V, decreasing the surface recombination and enhancing the photocurrent as
much as 180%.
PMID- 27503275
TI - Effect of pre-miRNA-1658 gene polymorphism on chicken growth and carcass traits.
AB - OBJECTIVE: Polymorphisms occurring in the precursor region of microRNAs (miRNAs)
affect the target gene and alter the biogenesis of miRNAs, resulting in
phenotypic variation. The purpose of the study was to investigate the genetic
effects of rs16681031 (C>G) mutation in the precursor region of gga-miR-1658 on
the economic traits of the Gushi-Anka chicken F2 resource population. METHODS: To
explore the effect of miR-1658 polymorphisms on chicken economic traits, the SNP
was genotyped by MassArray matrix-assisted laser desorption/ionization-time of
flight mass spectrometry. The association between the SNP and chicken body size,
growth and carcass traits was determined by linear mixed models. RESULTS: The SNP
was not only significantly associated with body weight at the age of 6, 8, 10, 12
weeks, respectively, but also with the breadth of the chicken chest, body
slanting length and pelvic breadth at 4 weeks, chest depth at 8 weeks of age, and
body slanting length at 12 weeks (p<0.05), respectively. CONCLUSION: Our data
serve as a useful resource for further analysis of miRNA function, and represent
a molecular genetic basis for poultry breeding.
PMID- 27503276
TI - Allosteric HIV-1 integrase inhibitors promote aberrant protein multimerization by
directly mediating inter-subunit interactions: Structural and thermodynamic
modeling studies.
AB - Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) bind at the dimer interface
of the IN catalytic core domain (CCD), and potently inhibit HIV-1 by promoting
aberrant, higher-order IN multimerization. Little is known about the structural
organization of the inhibitor-induced IN multimers and important questions
regarding how ALLINIs promote aberrant IN multimerization remain to be answered.
On the basis of physical chemistry principles and from our analysis of
experimental information, we propose that inhibitor-induced multimerization is
mediated by ALLINIs directly promoting inter-subunit interactions between the CCD
dimer and a C-terminal domain (CTD) of another IN dimer. Guided by this
hypothesis, we have built atomic models of inter-subunit interfaces in IN
multimers by incorporating information from hydrogen-deuterium exchange (HDX)
measurements to drive protein-protein docking. We have also developed a novel
free energy simulation method to estimate the effects of ALLINI binding on the
association of the CCD and CTD. Using this structural and thermodynamic modeling
approach, we show that multimer inter-subunit interface models can account for
several experimental observations about ALLINI-induced multimerization, including
large differences in the potencies of various ALLINIs, the mechanisms of
resistance mutations, and the crucial role of solvent exposed R-groups in the
high potency of certain ALLINIs. Our study predicts that CTD residues Tyr226,
Trp235 and Lys266 are involved in the aberrant multimer interfaces. The key
finding of the study is that it suggests the possibility of ALLINIs facilitating
inter-subunit interactions between an external CTD and the CCD-CCD dimer
interface.
PMID- 27503277
TI - The role of glycemia in insulin resistance in youth with type 1 and type 2
diabetes.
AB - BACKGROUND: Hyperglycemia has traditionally been considered a major contributor
to insulin resistance (IR) in type 1 diabetes (T1D), yet studies examining the
relationship between HbA1c and IR are conflicting. Glucose measures captured by
continuous glucose monitoring (CGM) (eg, peak glucose, standard deviation,
hypoglycemia) in youth have not been explored as predictors of insulin
sensitivity (IS). OBJECTIVE: Assess the relationship between IS and glycemia in
youth with T1D and type 2 diabetes (T2D). METHODS: Sedentary 12-19 year olds with
diabetes had peripheral IS measured by hyperinsulinemic-euglycemic clamp. HbA1c
and 3 days of CGM data were also collected. Spearman correlation coefficients
were calculated to examine the association between variables. RESULTS:
Participants included 100 youth with T1D [46% male, median body mass index (BMI)
74 percentile, HbA1c 8.5%] and 42 with T2D (26% male, BMI 99 percentile, HbA1c
6.9%). Nineteen with T1D and 13 with T2D also wore CGM. In T2D youth, higher
HbA1c, average sensor glucose, area under the CGM curve, and metabolic syndrome
characteristics correlated with lower IS. In T1D youth, higher BMI percentile,
waist circumference, triglycerides, and LDL cholesterol, but not HbA1c,
correlated with lower IS. Moreover, higher CGM overnight means glucose correlated
with greater IS, and CGM hypoglycemia correlated with lower IS. CONCLUSIONS:
Markers of metabolic syndrome and hyperglycemia predicted decreased IS in T2D
youth. Paradoxically, hypoglycemia predicted decreased IS in T1D youth and
hyperglycemia, particularly overnight, predicted improved IS. These preliminary
results imply different mechanisms underlying IR in T1D vs T2D and suggest a role
for non-insulin therapies in T1D to improve IR.
PMID- 27503278
TI - [Aplasia cutis congenita: Update and management].
AB - Congenital skin aplasia, or aplasia cutis congenita (ACC) is a rare congenital
disease. It is characterized by the absence of skin at birth, localized or
widespread, of one or several areas. This condition commonly involve the scalp
but can also involve more rarely the trunk or limbs. However it is most
frequently an isolated disorder, it can be associated with other anomalies, such
as the Adams-Oliver syndrome, the association with a fetus papyraceus or with an
epidermolysis bullosa. Many hypothesis have been suggested: vascular, genetic,
traumatic, pharmacological or an anomaly in the neural tube closure process, but
the exact mechanism is still unknown. Morbidity and mortality of this
malformation depends on the affected area and the size of the defect. The main
risk is the infection, hemorrhage and thrombosis in the case of a scalp defect
with an underlying bone defect, the exposure of the meninges and the superior
sagittal sinus. The initial management of ACC will therefore involve several
plastic surgery techniques, from more simple to more complex, using conservative
wound care to flaps techniques. Other techniques can be performed later, in the
management of ACC sequelae, such as skin expansion for scarring alopecia.
PMID- 27503279
TI - The solely motif-doped Au36-xAgx(SPh-tBu)24 (x = 1-8) nanoclusters: X-ray crystal
structure and optical properties.
AB - We report the observation of new doping behavior in Au36-xAgx(SR)24 nanoclusters
(NCs) with x = 1 to 8. The atomic arrangements of Au and Ag atoms are determined
by X-ray crystallography. The new gold-silver bimetallic NCs share the same
framework as that of the homogold counterpart, i.e. possessing an fcc-type Au28
kernel, four dimeric AuAg(SR)3 staple motifs and twelve simple bridging SR
ligands. Interestingly, all the Ag dopants in the Au36-xAgx(SR)24 NCs are
selectively incorporated into the surface motifs, which is in contrast to the
previously reported Au-Ag alloy structures with the Ag dopants preferentially
displacing the core gold atoms. This distinct doping behavior implies that the
previous assignments of an fcc Au28 core with four dimers and 12 bridging
thiolates for Au36(SR)24 are more justified than other assignments of core vs.
surface motifs. The UV-Vis adsorption spectrum of Au36-xAgx(SR)24 is almost the
same as that of Au36(SR)24, indicating that the Ag dopants in the motifs do not
change the optical properties. The similar UV-Vis spectra are further confirmed
by TD-DFT calculations. DFT also reveals that the energies of the HOMO and LUMO
of the motif-doped AuAg alloy NC are comparable to those of the homogold Au36 NC,
indicating that the electronic structure is not disturbed by the motif Ag
dopants. Overall, this study reveals a new silver-doping mode in alloy NCs.
PMID- 27503280
TI - Early recognition of coeliac disease through community pharmacies: a proof of
concept study.
AB - Setting Fifteen community pharmacies in the UK. Objective Proof of concept study
to test the use of community pharmacies for active case finding of patients with
coeliac disease. Methods Customers accessing over-the counter and prescription
medicines indicated in the treatment of possible symptoms of coeliac disease over
a 6 month period were offered a free point of care test. All patients were given
advice regarding the test results and those who tested positive were advised to
make an appointment with their general practitioner. Patients and pharmacists
involved in service provision were asked to complete a satisfaction survey.
Pharmacists were additionally invited to undertake interviews to better
understand their views on the service. Main outcome measures Feasibility of
service, acceptability to stakeholders and proportion testing positive for
coeliac disease. Results Of the 551 individuals tested, 52 (9.4 %) tested
positive. 277 (50.3 %) were tested for accessing irritable bowel syndrome
treatment, 142 (25.8 %) due to presenting for diarrhoea. The proportion of
patients testing positive with different symptoms or for different treatments
were similar. Of 43 customers who returned the satisfaction survey, all would
recommend the service to others, believing the community pharmacy to be a
suitable location. Community pharmacists believed that it enabled them to improve
relationships with their customers and that medical practices were receptive to
the service. Conclusion This proof of concept study has shown that community
pharmacies using a point of care test can effectively recognise and refer
patients for confirmatory coeliac disease testing with high levels of customer
and service provider satisfaction.
PMID- 27503281
TI - Patients' knowledge and attitude towards therapeutic reference pricing system in
Slovenia.
AB - Background The therapeutic reference pricing (TRP) in Slovenia was implemented
for proton pump inhibitors in 2013 and for angiotensin-converting enzyme
inhibitors and lipid-lowering medicines in 2014. Objective The study aimed to
assess patients' knowledge and attitude towards the TRP system. Moreover, the
patients' willingness to pay was evaluated for patients who rejected the
substitution of a current medicine within a therapeutic class by the reference
medicine for which no co-payment is needed. Setting Invitation of patients to
participate in a survey and filling in the first part of the questionnaire was
run in the community pharmacies in Slovenia. The second part of the questionnaire
was filled in at patients' home. Method A representative sample of 676 patients
that had been prescribed at least one medicine from the three therapeutic classes
was surveyed. The survey was carried out from 15th May to 15th June 2014 in 40
community pharmacies with the help of the pharmacists, who filled in the first
part of the questionnaire in the presence of the patients. The second part of the
questionnaire was filled in by 475 patients at home and returned by prepaid mail.
Main outcome measure Patients' knowledge of and attitude to the TRP system
implemented into Slovenian health care practice. Results Most of the statements
describing patient' rights and duties within the TRP system were known by
approximately 50 % of the patients. Patients were inhomogeneous in their view
about the necessity and benefits of the TRP system, most of them regarded it as
an unnecessary burden. Among 50.4 % of the patients who were required to copay
for their medicine, 46.7 % accepted and 3.7 % rejected co-payment. The average co
payment was ? 6.92, while the expressed average willingness to co-pay was ? 10.4
per 3 months of therapy. Conclusion Our results indicate that the implementation
of the TRP system and potential upgrades represent a significant challenge for
the patients.
PMID- 27503282
TI - Potentially inappropriate prescribing in nursing home residents detected with the
community pharmacist specific GheOP(3)S-tool.
AB - Background The Ghent Older People's Prescriptions community Pharmacy Screening
(GheOP3S-)tool was recently developed to screen for potentially inappropriate
prescribing (PIP). Objective We aimed (1) to determine PIP prevalence in older
nursing home (NH) residents with polypharmacy using the GheOP3S-tool and (2) to
identify those PIPs that are most frequently detected. Method A cross-sectional
study was carried out between February and June 2014 in 10 NHs in Belgium,
supplied by a community pharmacy chain. For each NH, 40 residents (>=70 years,
using >=5 chronic drugs) were included. PIP prevalence was determined using the
GheOP3S-tool. Results 400 NH residents were included [mean age (+/-SD) 86.2 (+/
6.3) years; median number of drugs (+/-IQR) 10 (7-12)]. A total of 1728 PIPs were
detected in 387 (97 %) participants (Median 4; IQR 2-6). The most prevalent items
can be assigned to three categories: long-term use of central nervous system
drugs (i.e. benzodiazepines, antidepressants and antipsychotics), use of
anticholinergic drugs (mutual combinations and with underlying
constipation/dementia) and underuse of osteoporosis prophylaxis. Conclusion
Screening for PIP by means of the GheOP3S-tool revealed a high prevalence of PIP
among older NH residents with polypharmacy. This finding urges for initiatives on
the patient-level, but also on a broader, institutional level.
PMID- 27503283
TI - Sources and magnitude of error in preparing morphine infusions for nurse-patient
controlled analgesia in a UK paediatric hospital.
AB - Background Administering nurse/patient controlled analgesia (N/PCA) to children
requires complex dose calculations and multiple manipulations to prepare morphine
solutions in 50 mL syringes for administration by continuous infusion with
additional boluses. Objective To investigate current practice and accuracy during
preparation of morphine N/PCA infusions in hospital theatres and wards at a UK
children's hospital. Methods Direct observation of infusion preparation methods
and morphine concentration quantification using UV-Vis spectrophotometry. The
British Pharmacopoeia specification for morphine sulphate injection drug content
(+/-7.5 %) was used as a reference limit. Results Preparation of 153 morphine
infusions for 128 paediatric patients was observed. Differences in preparation
method were identified, with selection of inappropriate syringe size noted. Lack
of appreciation of the existence of a volume overage (i.e. volume in excess of
the nominal volume) in morphine ampoules was identified. Final volume of the
infusion was greater than the target (50 mL) in 33.3 % of preparations. Of 78
infusions analysed, 61.5 % had a morphine concentration outside 92.5-107.5 % of
label strength. Ten infusions deviated by more than 20 %, with one by 100 %.
Conclusions Variation in morphine infusion preparation method was identified.
Lack of appreciation of the volume overage in ampoules, volumetric accuracy of
different syringe sizes and ability to perform large dilutions of small volumes
were sources of inaccuracy in infusion concentration, resulting in patients
receiving morphine doses higher or lower than prescribed.
PMID- 27503284
TI - Comment on: "Safety and Tolerability of Pharmacological Treatment of Alcohol
Dependence: Comprehensive Review of Evidence".
PMID- 27503285
TI - Authors' Reply to Alain Braillon's Comment on "Safety and Tolerability of
Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of
Evidence".
PMID- 27503286
TI - Patient-centeredness and its impact on patient satisfaction and treatment
outcomes in medical rehabilitation.
AB - OBJECTIVE: To examine the impact of patient-centeredness for patient satisfaction
and treatment outcomes. METHOD: A multicenter cross-sectional survey study with
patients (n=1033) in nine medical rehabilitation centers in Germany was
conducted. Data was analyzed with multiple linear regression. Predictors were
patient-centeredness (CCRQ-15) and patients age, employment and therapeutic
indication; outcomes were patient satisfaction and treatment outcomes (changes in
living conditions and health status). RESULTS: The regression model could explain
54% of variance in patient satisfaction. The strongest predictor was decision
making/communication (beta=0.34). In treatment outcome, 19% of variance of
changes in living conditions and 21% of variance of changes in state of health
could be explained. The strongest predictor in both variables was self
management/empowerment (beta=0.40 and 0.32, respectively). CONCLUSION: The
results emphasize the relevance of patient-centered treatments for patient
satisfaction and treatment results. The evidence is provided for the first time
in medical rehabilitation. PRACTICE IMPLICATIONS: Further studies should consider
multilevel modeling and diverse survey methods. Continued implementation and
evaluation of patient-centeredness in the medical rehabilitation treatment are
recommended measures. Promoting shared decision-making, effective clinician
patient communication, and increased patient empowerment are essential, e.g. by
patient education programs or staff training in shared decision-making.
PMID- 27503287
TI - "We'll call you when the results are in": Preferences for how medical test
results are delivered.
AB - OBJECTIVE: Whether healthy or sick, adults undergo frequent medical testing;
however, no guidelines currently exist as to how patients are informed of their
medical test results. This short report provides an initial look at how
healthcare professionals deliver medical test results and patient preferences
regarding these procedures. METHODS: We specifically focus on two options for
delivery of results: (1) open-ended timing, in which patients are contacted
without warning when test results become available; or (2) closed-ended timing,
in which patients are provided with a specific day and time when they will learn
their test results. Participants who underwent a recent medical test indicated
which delivery method their healthcare professional provided and their preferred
method. RESULTS: Findings demonstrate a large discrepancy between actual and
preferred timing, stemming from a general trend towards providing open-ended
timing, whereas patient preferences were evenly split between the two options.
CONCLUSION: This study provides a first step in understanding the merits of two
options for delivering medical test results to patients and suggests an
opportunity to improve patient care. PRACTICE IMPLICATIONS: The findings from
this study provide first steps toward the development of guidelines for
delivering test results in ways that maximize the quality of patient care.
PMID- 27503288
TI - Identification of susceptibility gene associated with female primary Sjogren's
syndrome in Han Chinese by genome-wide association study.
AB - Primary Sjogren's syndrome (PSS) is an autoimmune disease targeting exocrine
glands. It ten times more dominantly affects women than men with an onset peak at
menopause. The genetic factor predisposing women to PSS remains unclear.
Therefore, we aimed to identify susceptibility loci for PSS in women. We
performed genome-wide association study (GWAS) using 242 female PSS patients and
1444 female control in Han Chinese population residing in Taiwan. Replication was
conducted in an independent cohort of 178 female PSS and 14,432 control subjects.
We identified rs117026326 on GTF2I with GWAS significance (P = 1.10 * 10-15) and
rs13079920 on RBMS3 with suggestive significance (P = 2.90 * 10-5) associating
with PSS in women. The association of RBMS3 was further evidenced by imputation
in which rs13072846 (P = 4.89 * 10-5) was identified and confirmed as female PSS
associating SNP within the same LD with rs13079920. PSS pathogenesis involves
both immune (effector) and exocrine (target) system. We suggested that while
GTF2I is a previously reported associating gene which may function in immune
system, RBMS3 is a novel susceptibility gene that predisposes women to PSS
potentially through modulating acinar apoptosis and TGF-beta signaling in target
exocrine system.
PMID- 27503289
TI - Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, cause
severe primary microcephaly in humans.
AB - Primary microcephaly is a clinical phenotype in which the head circumference is
significantly reduced at birth due to abnormal brain development, primarily at
the cortical level. Despite the marked genetic heterogeneity, most primary
microcephaly-linked genes converge on mitosis regulation. Two consanguineous
families segregating the phenotype of severe primary microcephaly, spasticity and
failure to thrive had overlapping autozygomes in which exome sequencing
identified homozygous splicing variants in CIT that segregate with the phenotype
within each family. CIT encodes citron, an effector of the Rho signaling that is
required for cytokinesis specifically in proliferating neuroprogenitors, as well
as for postnatal brain development. In agreement with the critical role assigned
to the kinase domain in effecting these biological roles, we show that both
splicing variants predict variable disruption of this domain. The striking
phenotypic overlap between CIT-mutated individuals and the knockout mice and rats
that are specifically deficient in the kinase domain supports the proposed causal
link between CIT mutation and primary microcephaly in humans.
PMID- 27503290
TI - Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute
to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic
Divergence of Homo sapiens.
AB - Thousands of candidate human-specific regulatory sequences (HSRS) have been
identified, supporting the hypothesis that unique to human phenotypes result from
human-specific alterations of genomic regulatory networks. Collectively, a
compendium of multiple diverse families of HSRS that are functionally and
structurally divergent from Great Apes could be defined as the backbone of human
specific genomic regulatory networks. Here, the conservation patterns analysis of
18,364 candidate HSRS was carried out requiring that 100% of bases must remap
during the alignments of human, chimpanzee, and bonobo sequences. A total of
5,535 candidate HSRS were identified that are: (i) highly conserved in Great
Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii)
defined by either the acceleration of mutation rates on the human lineage or the
functional divergence from non-human primates. The exaptation of highly conserved
ancestral DNA pathway seems mechanistically distinct from the evolution of
regulatory DNA segments driven by the species-specific expansion of transposable
elements. Genome-wide proximity placement analysis of HSRS revealed that a small
fraction of topologically associating domains (TADs) contain more than half of
HSRS from four distinct families. TADs that are enriched for HSRS and termed
rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the
hESC genome. RevTADs manifest distinct correlation patterns between placements of
human accelerated regions, human-specific transcription factor-binding sites, and
recombination rates. There is a significant enrichment within revTAD boundaries
of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII
binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS
in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis
supports the idea that phenotypic divergence of Homo sapiens is driven by the
evolution of human-specific genomic regulatory networks via at least two
mechanistically distinct pathways of creation of divergent sequences of
regulatory DNA: (i) recombination-associated exaptation of the highly conserved
ancestral regulatory DNA segments; (ii) human-specific insertions of transposable
elements.
PMID- 27503291
TI - Inevitability of Genetic Parasites.
AB - Almost all cellular life forms are hosts to diverse genetic parasites with
various levels of autonomy including plasmids, transposons and viruses.
Theoretical modeling of the evolution of primordial replicators indicates that
parasites (cheaters) necessarily evolve in such systems and can be kept at bay
primarily via compartmentalization. Given the (near) ubiquity, abundance and
diversity of genetic parasites, the question becomes pertinent: are such
parasites intrinsic to life? At least in prokaryotes, the persistence of
parasites is linked to the rate of horizontal gene transfer (HGT). We
mathematically derive the threshold value of the minimal transfer rate required
for selfish element persistence, depending on the element duplication and loss
rates as well as the cost to the host. Estimation of the characteristic gene
duplication, loss and transfer rates for transposons, plasmids and virus-related
elements in multiple groups of diverse bacteria and archaea indicates that most
of these rates are compatible with the long term persistence of parasites.
Notably, a small but non-zero rate of HGT is also required for the persistence of
non-parasitic genes. We hypothesize that cells cannot tune their horizontal
transfer rates to be below the threshold required for parasite persistence
without experiencing highly detrimental side-effects. As a lower boundary to the
minimum DNA transfer rate that a cell can withstand, we consider the process of
genome degradation and mutational meltdown of populations through Muller's
ratchet. A numerical assessment of this hypothesis suggests that microbial
populations cannot purge parasites while escaping Muller's ratchet. Thus, genetic
parasites appear to be virtually inevitable in cellular organisms.
PMID- 27503292
TI - Diurnal Transcriptional Regulation of Endosymbiotically Derived Genes in the
Chlorarachniophyte Bigelowiella natans.
AB - Chlorarachniophyte algae possess complex plastids acquired by the secondary
endosymbiosis of a green alga, and the plastids harbor a relict nucleus of the
endosymbiont, the so-called nucleomorph. Due to massive gene transfer from the
endosymbiont to the host, many proteins involved in plastid and nucleomorph are
encoded by the nuclear genome. Genome sequences have provided a blueprint for the
fate of endosymbiotically derived genes; however, transcriptional regulation of
these genes remains poorly understood. To gain insight into the evolution of
endosymbiotic genes, we performed genome-wide transcript profiling along the cell
cycle of the chlorarachniophyte Bigelowiella natans, synchronized by light and
dark cycles. Our comparative analyses demonstrated that transcript levels of
7,751 nuclear genes (35.7% of 21,706 genes) significantly oscillated along the
diurnal/cell cycles, and those included 780 and 147 genes for putative plastid
and nucleomorph-targeted proteins, respectively. Clustering analysis of those
genes revealed the existence of transcriptional networks related to specific
biological processes such as photosynthesis, carbon metabolism, translation, and
DNA replication. Interestingly, transcripts of many plastid-targeted proteins in
B. natans were induced before dawn, unlike other photosynthetic organisms. In
contrast to nuclear genes, 99% nucleomorph genes were found to be constitutively
expressed during the cycles. We also found that the nucleomorph DNA replication
would be controlled by a nucleus-encoded viral-like DNA polymerase. The results
of this study suggest that nucleomorph genes have lost transcriptional regulation
along the diurnal cycles, and nuclear genes exert control over the complex
plastid including the nucleomorph.
PMID- 27503293
TI - Multiple Lines of Evidence from Mitochondrial Genomes Resolve Phylogenetic
Relationships of Parasitic Wasps in Braconidae.
AB - The rapid increase in the number of mitochondrial genomes in public databases
provides opportunities for insect phylogenetic studies; but it also provides
challenges because of gene rearrangements and variable substitution rates among
both lineages and sites. Typically, phylogenetic studies use mitochondrial
sequence data but exclude other features of the mitochondrial genome from
analyses. Here, we undertook large-scale sequencing of mitochondrial genomes from
a worldwide collection of specimens belonging to Braconidae, one of the largest
families of Metazoa. The strand-asymmetry of base composition in the
mitochondrial genomes of braconids is reversed, providing evidence for monophyly
of the Braconidae. We have reconstructed a backbone phylogeny of the major
lineages of Braconidae from gene order of the mitochondrial genomes. Standard
phylogenetic analyses of DNA sequences provided strong support for both
Cyclostomes and Noncyclostomes. Four subfamily complexes, that is, helconoid,
euphoroid, sigalphoid, and microgastroid, within the Noncyclostomes were
reconstructed robustly, the first three of which formed a monophyletic group
sister to the last one. Aphidiinae was recovered as a lineage sister to other
groups of Cyclostomes, while the Ichneutinae was recovered as paraphyletic.
Separate analyses of the subdivided groups showed congruent relationships,
employing different matrices and methods, for the internal nodes of the
Cyclostomes and the microgastroid complex of subfamilies. This research, using
multiple lines of evidence from mitochondrial genomes, illustrates multiple uses
of mitochondrial genomes for phylogenetic inference in Braconidae.
PMID- 27503294
TI - Epigenetic Variability across Human Populations: A Focus on DNA Methylation
Profiles of the KRTCAP3, MAD1L1 and BRSK2 Genes.
AB - Natural epigenetic diversity has been suggested as a key mechanism in
microevolutionary processes due to its capability to create phenotypic
variability within individuals and populations. It constitutes an important
reservoir of variation potentially useful for rapid adaptation in response to
environmental stimuli. The analysis of population epigenetic structure represents
a possible tool to study human adaptation and to identify external factors that
are able to naturally shape human DNA methylation variability. The aim of this
study is to investigate the dynamics that create epigenetic diversity between and
within different human groups. To this end, we first used publicly available
epigenome-wide data to explore population-specific DNA methylation changes that
occur at macro-geographic scales. Results from this analysis suggest that
nutrients, UVA exposure and pathogens load might represent the main environmental
factors able to shape DNA methylation profiles. Then, we evaluated DNA
methylation of candidate genes (KRTCAP3, MAD1L1, and BRSK2), emerged from the
previous analysis, in individuals belonging to different populations from
Morocco, Nigeria, Philippines, China, and Italy, but living in the same Italian
city. DNA methylation of the BRSK2 gene is significantly different between
Moroccans and Nigerians (pairwise t-test: CpG 6 P-value = 5.2*10 (-) (3); CpG 9 P
value = 2.6*10 (-) (3); CpG 10 P-value = 3.1*10 (-) (3); CpG 11 P-value = 2.8*10
(-) (3)). Comprehensively, these results suggest that DNA methylation diversity
is a source of variability in human groups at macro and microgeographical scales
and that population demographic and adaptive histories, as well as the individual
ancestry, actually influence DNA methylation profiles.
PMID- 27503295
TI - The Role of Retrotransposons in Gene Family Expansions in the Human and Mouse
Genomes.
AB - Retrotransposons comprise a large portion of mammalian genomes. They contribute
to structural changes and more importantly to gene regulation. The expansion and
diversification of gene families have been implicated as sources of evolutionary
novelties. Given the roles retrotransposons play in genomes, their contribution
to the evolution of gene families warrants further exploration. In this study, we
found a significant association between two major retrotransposon classes, LINEs
and LTRs, and lineage-specific gene family expansions in both the human and mouse
genomes. The distribution and diversity differ between LINEs and LTRs, suggesting
that each has a distinct involvement in gene family expansion. LTRs are
associated with open chromatin sites surrounding the gene families, supporting
their involvement in gene regulation, whereas LINEs may play a structural role
promoting gene duplication. Our findings also suggest that gene family
expansions, especially in the mouse genome, undergo two phases. The first phase
is characterized by elevated deposition of LTRs and their utilization in
reshaping gene regulatory networks. The second phase is characterized by rapid
gene family expansion due to continuous accumulation of LINEs and it appears
that, in some instances at least, this could become a runaway process. We provide
an example in which this has happened and we present a simulation supporting the
possibility of the runaway process. Altogether we provide evidence of the
contribution of retrotransposons to the expansion and evolution of gene families.
Our findings emphasize the putative importance of these elements in
diversification and adaptation in the human and mouse lineages.
PMID- 27503296
TI - Comparative Large-Scale Mitogenomics Evidences Clade-Specific Evolutionary Trends
in Mitochondrial DNAs of Bivalvia.
AB - Despite the figure of complete bivalve mitochondrial genomes keeps growing, an
assessment of the general features of these genomes in a phylogenetic framework
is still lacking, despite the fact that bivalve mitochondrial genomes are unusual
under different aspects. In this work, we constructed a dataset of one hundred
mitochondrial genomes of bivalves to perform the first systematic comparative
mitogenomic analysis, developing a phylogenetic background to scaffold the
evolutionary history of the class' mitochondrial genomes. Highly conserved
domains were identified in all protein coding genes; however, four genes (namely,
atp6, nad2, nad4L, and nad6) were found to be very divergent for many respects,
notwithstanding the overall purifying selection working on those genomes.
Moreover, the atp8 gene was newly annotated in 20 mitochondrial genomes, where it
was previously declared as lacking or only signaled. Supernumerary mitochondrial
proteins were compared, but it was possible to find homologies only among
strictly related species. The rearrangement rate on the molecule is too high to
be used as a phylogenetic marker, but here we demonstrate for the first time in
mollusks that there is correlation between rearrangement rates and evolutionary
rates. We also developed a new index (HERMES) to estimate the amount of
mitochondrial evolution. Many genomic features are phylogenetically congruent and
this allowed us to highlight three main phases in bivalve history: the origin,
the branching of palaeoheterodonts, and the second radiation leading to the
present-day biodiversity.
PMID- 27503297
TI - Weak Polygenic Selection Drives the Rapid Adaptation of the Chemosensory System:
Lessons from the Upstream Regions of the Major Gene Families.
AB - The animal chemosensory system is involved in essential biological processes,
most of them mediated by proteins encoded in multigene families. These multigene
families have been fundamental for the adaptation to new environments,
significantly contributing to phenotypic variation. This adaptive potential
contrasts, however, with the lack of studies at their upstream regions,
especially taking into account the evidence linking their transcriptional changes
to certain phenotypic effects. Here, we explicitly characterize the contribution
of the upstream sequences of the major chemosensory gene families to rapid
adaptive processes. For that, we analyze the genome sequences of 158 lines from a
population of Drosophila melanogaster that recently colonized North America, and
integrate functional and transcriptional data available for this species. We find
that both, strong negative and strong positive selection, shape transcriptional
evolution at the genome-wide level. The chemosensory upstream regions, however,
exhibit a distinctive adaptive landscape, including multiple mutations of small
beneficial effect and a reduced number of cis-regulatory elements. Together, our
results suggest that the promiscuous and partially redundant transcription and
function of the chemosensory genes provide evolutionarily opportunities for rapid
adaptive episodes through weak polygenic selection.
PMID- 27503298
TI - Mitochondrion-to-Chloroplast DNA Transfers and Intragenomic Proliferation of
Chloroplast Group II Introns in Gloeotilopsis Green Algae (Ulotrichales,
Ulvophyceae).
AB - To probe organelle genome evolution in the Ulvales/Ulotrichales clade, the newly
sequenced chloroplast and mitochondrial genomes of Gloeotilopsis planctonica and
Gloeotilopsis sarcinoidea (Ulotrichales) were compared with those of
Pseudendoclonium akinetum (Ulotrichales) and of the few other green algae
previously sampled in the Ulvophyceae. At 105,236 bp, the G planctonica
mitochondrial DNA (mtDNA) is the largest mitochondrial genome reported so far
among chlorophytes, whereas the 221,431-bp G planctonica and 262,888-bp G
sarcinoidea chloroplast DNAs (cpDNAs) are the largest chloroplast genomes
analyzed among the Ulvophyceae. Gains of non-coding sequences largely account for
the expansion of these genomes. Both Gloeotilopsis cpDNAs lack the inverted
repeat (IR) typically found in green plants, indicating that two independent IR
losses occurred in the Ulvales/Ulotrichales. Our comparison of the
Pseudendoclonium and Gloeotilopsis cpDNAs offered clues regarding the mechanism
of IR loss in the Ulotrichales, suggesting that internal sequences from the rDNA
operon were differentially lost from the two original IR copies during this
process. Our analyses also unveiled a number of genetic novelties. Short mtDNA
fragments were discovered in two distinct regions of the G sarcinoidea cpDNA,
providing the first evidence for intracellular inter-organelle gene migration in
green algae. We identified for the first time in green algal organelles, group II
introns with LAGLIDADG ORFs as well as group II introns inserted into
untranslated gene regions. We discovered many group II introns occupying sites
not previously documented for the chloroplast genome and demonstrated that a
number of them arose by intragenomic proliferation, most likely through
retrohoming.
PMID- 27503300
TI - Feasibility of triphasic CT with a modified two-point Patlak plot to determine
spit kidney glomerular filtration rate in clinical practice.
AB - PURPOSE: To investigate whether triphasic CT with a simplified Patlak plot can be
used in clinical practice for the estimate of split kidney glomerular filtration
rate (SKGFR). MATERIALS AND METHODS: The animal experiment included 15 rabbits
that underwent 40 dynamic contrast-enhanced CT scans of the kidneys with 1.5 s
time interval. Patlak-derived SKGFR was obtained using standard forty-point, two
point (unenhanced phase, arterial phase t alpha, and portovenous phase t beta),
and a modified two-point (MTP) (unenhanced, t alpha, t beta, and a virtual t tau
[t tau = (t alpha + t beta)/2]) image data, respectively. The MTP-Patlak plot
approach was then validated in 13 patients who underwent a triphasic renal
contrast-enhanced CT examination. SKGFR measured by 99mTc-DTPA clearance was as a
standard reference. RESULTS: MTP-Patlak significantly reduced input function
errors than two-point Patlak (21.1 +/- 16.2 % vs 30.8 +/- 15.2 %, p < 0.01) and
showed good concordance with standard Patlak for measurement of SKGFR in animal
experiment (1.20 +/- 0.38 mL/g/min vs 1.51 +/- 0.43 mL/g/min; linear correlation
coefficient r = 0.87, p < 0.001). Human study showed that mean SKGFR was 45.7
mL/min (range, 26.5-86.2 mL/min) obtained from 99mTc-DTPA, and 38.2 mL/min
(range, 18.6-79.3 mL/min) obtained from triphasic CT using MTP-Patlak plot.
Linear correlation between the two methods was r = 0.75 (p < 0.01). The mean
difference between SKGFRs as determined with the two methods was 7.4 +/- 9.0
mL/min. CONCLUSION: The MTP-Patlak approach, featured with simplicity, is
feasible in a clinically indicated CT examination for the evaluation of split
renal function.
PMID- 27503299
TI - Comparative Metagenomic Analysis Reveals Mechanisms for Stress Response in
Hypoliths from Extreme Hyperarid Deserts.
AB - Understanding microbial adaptation to environmental stressors is crucial for
interpreting broader ecological patterns. In the most extreme hot and cold
deserts, cryptic niche communities are thought to play key roles in ecosystem
processes and represent excellent model systems for investigating microbial
responses to environmental stressors. However, relatively little is known about
the genetic diversity underlying such functional processes in climatically
extreme desert systems. This study presents the first comparative metagenome
analysis of cyanobacteria-dominated hypolithic communities in hot (Namib Desert,
Namibia) and cold (Miers Valley, Antarctica) hyperarid deserts. The most abundant
phyla in both hypolith metagenomes were Actinobacteria, Proteobacteria,
Cyanobacteria and Bacteroidetes with Cyanobacteria dominating in Antarctic
hypoliths. However, no significant differences between the two metagenomes were
identified. The Antarctic hypolithic metagenome displayed a high number of
sequences assigned to sigma factors, replication, recombination and repair,
translation, ribosomal structure, and biogenesis. In contrast, the Namib Desert
metagenome showed a high abundance of sequences assigned to carbohydrate
transport and metabolism. Metagenome data analysis also revealed significant
divergence in the genetic determinants of amino acid and nucleotide metabolism
between these two metagenomes and those of soil from other polar deserts, hot
deserts, and non-desert soils. Our results suggest extensive niche
differentiation in hypolithic microbial communities from these two extreme
environments and a high genetic capacity for survival under environmental
extremes.
PMID- 27503301
TI - The Simple Video Coder: A free tool for efficiently coding social video data.
AB - Videotaping of experimental sessions is a common practice across many disciplines
of psychology, ranging from clinical therapy, to developmental science, to animal
research. Audio-visual data are a rich source of information that can be easily
recorded; however, analysis of the recordings presents a major obstacle to
project completion. Coding behavior is time-consuming and often requires ad-hoc
training of a student coder. In addition, existing software is either
prohibitively expensive or cumbersome, which leaves researchers with inadequate
tools to quickly process video data. We offer the Simple Video Coder-free, open
source software for behavior coding that is flexible in accommodating different
experimental designs, is intuitive for students to use, and produces outcome
measures of event timing, frequency, and duration. Finally, the software also
offers extraction tools to splice video into coded segments suitable for training
future human coders or for use as input for pattern classification algorithms.
PMID- 27503302
TI - Spanish semantic feature production norms for 400 concrete concepts.
AB - Semantic feature production norms provide many quantitative measures of different
feature and concept variables that are necessary to solve some debates
surrounding the nature of the organization, both normal and pathological, of
semantic memory. Despite the current existence of norms for different languages,
there are still no published norms in Spanish. This article presents a new set of
norms collected from 810 participants for 400 living and nonliving concepts among
Spanish speakers. These norms consist of empirical collections of features that
participants used to describe the concepts. Four files were elaborated: a concept
feature file, a concept-concept matrix, a feature-feature matrix, and a
significantly correlated features file. We expect that these norms will be useful
for researchers in the fields of experimental psychology, neuropsychology, and
psycholinguistics.
PMID- 27503303
TI - Sgttoolbox: Utility for controlling SimpleGazeTracker from Psychtoolbox.
AB - Eye movement analysis is effective for investigating visual perception and
cognition. The cost of conducting eye movement studies has decreased as a result
of the recent release of low-cost commercial and open-source eye trackers.
However, synchronizing visual stimulus presentation with eye movement recording
is still difficult, particularly if the eye tracker does not come with a
practical application programming interface. This paper introduces a
Matlab/Octave toolbox named Sgttoolbox, which works in conjunction with the
widely used experiment control library Psychtoolbox to control a cross-platform
open-source eye tracker named SimpleGazeTracker, which is an eye-tracking
application of GazeParser software. Hardware and software requirements for
Sgttoolbox and its main functions are described. A test of temporal accuracy
showed that eye movement sampling frequency was stable when stimulus presentation
and recording were performed on a single PC, although better performance was
obtained when presentation and recording were performed on separate PCs.
Transferring the latest eye position from SimpleGazeTracker to Psychtoolbox
script takes 2 to 4 ms on average, which causes a delay in drawing multiple
visual stimuli when recording and stimulus presentation were performed on a
single PC. When such a transfer delay is not importnat, Sgttoolbox would be a
good choice for Psychtoolbox users who wish to conduct eye-tracking studies.
PMID- 27503304
TI - Statistical analyses of the resilience function.
AB - The extent to which distracting information influences decisions can be
informative about the nature of the underlying cognitive and perceptual
processes. In a recent paper, a response time-based measure for quantifying the
degree of interference (or facilitation) from distracting information termed
resilience was introduced. Despite using a statistical measure, the analysis was
limited to qualitative comparisons between different model predictions. In this
paper, we demonstrate how statistical procedures from workload capacity analysis
can be applied to the new resilience functions. In particular, we present an
approach to null-hypothesis testing of resilience functions and a method based on
functional principal components analysis for analyzing differences in the
functional form of the resilience functions across participants and conditions.
PMID- 27503305
TI - Clinical significance of noncalcified lung nodules in patients with breast
cancer.
AB - Patients with breast cancer are increasingly likely to have chest computed
tomography (CT) performed. In many cases, small lung nodules will be detected,
raising concern for metastases and causing considerable patient anxiety. The
majority of these nodules, however, are benign, though the specific probability
of malignancy is uncertain in any given case. Therefore, we analyzed the results
of chest CT scans of a large number of patients with breast cancer, to determine
characteristics and clinical significance of noncalcified lung nodules. 3313
patients were investigated, and 4889 CT scans from 1325 patients were
retrospectively reviewed. Among the 1325 patients, 812 (59 %) had at least one
noncalcified lung nodule, of which 330 (41 %) had malignant nodules, 197 (24 %)
had large (>=10 mm) nodules, and 586 (72 %) had multiple nodules. Large nodules
were more often malignant than benign (P < 0.001). In patients with multiple
large nodules, the rate of malignancy rate was 83 %, and most of these were
metastases. In the case of very small (2-4 mm) nodules, the malignancy rates for
solitary and multiple nodules were 8 and 20 %, respectively. Lung metastases were
more likely with breast cancer cell grade 3 (22 %) than grade 1-2 (10 %) (P <
0.001) and when patients were clinical stage 2-3 (14 %) than stage 0-1 (7.9 %) (P
= 0.03). Lung metastases are highly likely in patients with multiple nodules
greater than 10 mm. Higher cancer cell grades and clinical stage are also related
to an increased likelihood of lung metastases. The great majority of small lung
nodules in breast cancer patients are benign.
PMID- 27503306
TI - [Preclinical fibrinolysis in patients with ST-segment elevation myocardial
infarction in a rural region].
AB - BACKGROUND: In the current guidelines for the treatment of patients with ST
segment elevation myocardial infarction (STEMI), the European Society of
Cardiology (ESC) recommends preclinical fibrinolysis as a reperfusion therapy if,
due to long transportation times, no cardiac catheterisation is available within
90-120 min. However, there is little remaining in-depth expertise in this method
because fibrinolysis is presently only rarely indicated. METHODS: In a rural area
in southwestern Germany, where an emergency primary percutaneous coronary
intervention was not routinely available within 90-120 min, 156 STEMI patients
underwent fibrinolysis with the plasminogen activator reteplase, performed by
trained emergency physicians. The practicality of the treatment, as well as
complications and the mortality of the patients in the preclinical phase until
arrival at the hospital, were retrospectively studied. RESULTS: The mean time
from onset of the symptoms to first medical contact was 114 +/- 116 min. The mean
interval to the start of fibrinolysis of 13.5 +/- 6.4 min was within the 30 min
mandated by the ESC. Patients with inferior STEMI represented the largest
subgroup. Occurring in 39 cases (25 %), complications due to infarction were
relatively common during the prehospital phase, including 15 cases (9.6 %) of
cardiogenic shock, but in all cases the complications were manageable. No patient
died before arrival at the hospital. As lysis-associated adverse effects, merely
two uncomplicated mucosal haemorrhages and one case of mild allergic skin
reactions were seen. CONCLUSION: In emergency situations with long transportation
times to the nearest suitable cardiac catheterisation laboratory, preclinical
fibrinolysis in STEMI still represents a workable method. Success of this
strategy requires particularly strong training of the emergency physicians in ECG
and lysis therapy, and co-operation with nearby cardiac centres.
PMID- 27503307
TI - The association between ambient temperature and preterm birth in Shenzhen, China:
a distributed lag non-linear time series analysis.
AB - BACKGROUND: A few studies have examined the association between ambient
temperature and preterm birth (PTB), and the results have been inconsistent. This
study explored the association between ambient temperature and PTB in Shenzhen,
China. METHODS: Data of daily singleton PTB, air pollution and meteorological
variables from 2005 to 2011 were collected in Shenzhen. A distributed lag non
linear model (DLNM) was used to investigate the association of the low and high
temperatures (1st, 5th, 95th, and 99th percentiles) with PTB. RESULTS: The median
temperature was 24.5 degrees C and the 1st, 5th, 95th, and 99th percentiles of
daily mean temperatures were 9, 12.5, 29.9 and 30.7 degrees C, respectively. The
prevalence of singleton PTB was 5.61 % in Shenzhen. The association between
temperature and PTB was not linear. There was an immediate positive association
of low temperature (1st and 5th percentiles) and a negative association of high
temperature (95th and 99th percentiles) with PTB. The effect of low temperature 9
degrees C (1st) on PTB on the current day was stronger than that of 12.5
degrees C (5th), with a relative risk (RR) of 1.54 (95 % CI: 1.36-1.75) and 1.49
(95 % CI: 1.35-1.63), respectively. The cumulative RR (up to 30 days) of 9 and
12.5 degrees C was 1.72 (95 % CI: 1.28-2.33) and 1.96 (95 % CI: 1.60-2.39),
respectively. The cumulative effects (up to 30 days) of high temperature (95th
and 99th percentiles) on PTB were 0.69 (95 % CI: 0.60-0.80) and 0.62 (95 % CI:
0.52-0.74), respectively. The cumulative effect (up to 30 days) of low
temperatures on vaginal delivery PTB was lower than that of the cesarean section
PTB with an RR of 1.58 (95 % CI: 1.12-2.22) and 1.93 (95 % CI: 1.21-3.08),
respectively. CONCLUSIONS: This study suggests that low temperature might be a
risk factor, while high temperature might be a protective factor of PTB in
Shenzhen.
PMID- 27503308
TI - Diffusion-weighted echo planar MR imaging of the neck at 3 T using integrated
shimming: comparison of MR sequence techniques for reducing artifacts caused by
magnetic-field inhomogeneities.
AB - OBJECTIVE: Our objective was to compare available techniques reducing artifacts
in echo planar imaging (EPI)-based diffusion-weighed magnetic resonance imaging
MRI (DWI) of the neck at 3 Tesla caused by B0-field inhomogeneities. MATERIALS
AND METHODS: A cylindrical fat-water phantom was equipped with a Maxwell coil
allowing for additional linear B0-field variations in z-direction. The effect of
increasing strength of this superimposed gradient on image quality was observed
using a standard single-shot EPI-based DWI sequence (sEPI), a zoomed single-shot
EPI sequence (zEPI), a readout-segmented EPI sequence (rsEPI), and an sEPI
sequence with integrated dynamic shimming (intEPI) on a 3-Tesla system.
Additionally, ten volunteers were examined over the neck region using these
techniques. Image quality was assessed by two radiologists. Scan durations were
recorded. RESULTS: With increasing strength of the external gradient, marked
distortions, signal loss, and failure of fat suppression were observed using
sEPI, zEPI, and rsEPI. These artifacts were markedly reduced using intEPI.
Significantly better in vivo image quality was also observed using intEPI
compared with the other techniques. Scan time of intEPI was similar to sEPI and
zEPI and shorter than rsEPI. CONCLUSION: The use of integrated 2D shim and
frequency adjustment for EPI-based DWI results in a significant improvement in
image quality of the head/neck region at 3 Tesla. Combining integrated shimming
with rsEPI or zEPI can be expected to provide additional improvements.
PMID- 27503309
TI - 3D single point imaging with compressed sensing provides high temporal resolution
R 2* mapping for in vivo preclinical applications.
AB - OBJECTIVE: Purely phase-encoded techniques such as single point imaging (SPI) are
generally unsuitable for in vivo imaging due to lengthy acquisition times.
Reconstruction of highly undersampled data using compressed sensing allows SPI
data to be quickly obtained from animal models, enabling applications in
preclinical cellular and molecular imaging. MATERIALS AND METHODS: TurboSPI is a
multi-echo single point technique that acquires hundreds of images with
microsecond spacing, enabling high temporal resolution relaxometry of large-R 2*
systems such as iron-loaded cells. TurboSPI acquisitions can be pseudo-randomly
undersampled in all three dimensions to increase artifact incoherence, and can
provide prior information to improve reconstruction. We evaluated the performance
of CS-TurboSPI in phantoms, a rat ex vivo, and a mouse in vivo. RESULTS: An
algorithm for iterative reconstruction of TurboSPI relaxometry time courses does
not affect image quality or R 2* mapping in vitro at acceleration factors up to
10. Imaging ex vivo is possible at similar acceleration factors, and in vivo
imaging is demonstrated at an acceleration factor of 8, such that acquisition
time is under 1 h. CONCLUSIONS: Accelerated TurboSPI enables preclinical R 2*
mapping without loss of data quality, and may show increased specificity to iron
oxide compared to other sequences.
PMID- 27503310
TI - Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and
Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner.
AB - Endothelial activation with excessive recruitment and adhesion of immune cells
plays a central role in the progression of sepsis. We established a microfluidic
system to study the activation of human umbilical vein endothelial cells by
conditioned medium containing plasma from lipopolysaccharide-stimulated whole
blood or from septic blood and to investigate the effect of adsorption of
inflammatory mediators on endothelial activation. Treatment of stimulated whole
blood with polystyrene-divinylbenzene-based cytokine adsorbents (average pore
sizes 15 or 30 nm) prior to passage over the endothelial layer resulted in
significantly reduced endothelial cytokine and chemokine release, plasminogen
activator inhibitor-1 secretion, adhesion molecule expression, and in diminished
monocyte adhesion. Plasma samples from sepsis patients differed substantially in
their potential to induce endothelial activation and monocyte adhesion despite
their almost identical interleukin-6 and tumor necrosis factor-alpha levels. Pre
incubation of the plasma samples with a polystyrene-divinylbenzene-based
adsorbent (30 nm average pore size) reduced endothelial intercellular adhesion
molecule-1 expression to baseline levels, resulting in significantly diminished
monocyte adhesion. Our data support the potential of porous polystyrene
divinylbenzene-based adsorbents to reduce endothelial activation under septic
conditions by depletion of a broad range of inflammatory mediators.
PMID- 27503311
TI - Children's supernatural thinking as a signalling behaviour in early childhood.
AB - In this study, we analysed the reaction times of 137 college students when making
decisions on pairs of hypothetical children verbalizing different types of
vignettes and/or exhibiting different physical appearance (photographs of faces).
Vignettes depicted immature and mature versions of both supernatural (e.g., 'The
sun's not out today because it's mad' vs. 'The sun's not out today because the
clouds are blocking it') and natural ('I can remember all 20 cards!' vs. 'I can
remember 6 or 7 cards') explanations to ordinary phenomena. Photographs of
children's faces were morphed with a physical appearance of approximately 4-7
years old or approximately 8-10 years old. In earlier research, immature
supernatural thinking produced positive-affect reactions from adults and older
adolescents (14-18 years old) towards young children, with cognitive cues being
more important than physical-appearance cues in influencing adults' judgements.
Reaction times to make decisions varied for the Supernatural and Natural
vignettes and for the immature and mature vignettes/faces, reflecting the
differential cognitive effort adults used for making decisions about aspects of
children's physical appearance and verbal expressions. The findings were
interpreted in terms of the critical role that young children's immature
supernatural thinking has on adults' perception, analogous to the evolved role of
immature physical features on adults' perception of infants.
PMID- 27503312
TI - ProBDNF inhibits collective migration and chemotaxis of rat Schwann cells.
AB - Schwann cell migration, including collective migration and chemotaxis, is
essential for the formation of coordinate interactions between Schwann cells and
axons during peripheral nerve development and regeneration. Moreover, limited
migration of Schwann cells imposed a serious obstacle on Schwann cell-astrocytes
intermingling and spinal cord repair after Schwann cell transplantation into
injured spinal cords. Recent studies have shown that mature brain-derived
neurotrophic factor, a member of the neurotrophin family, inhibits Schwann cell
migration. The precursor form of brain-derived neurotrophic factor, proBDNF, was
expressed in the developing or degenerating peripheral nerves and the injured
spinal cords. Since "the yin and yang of neurotrophin action" has been
established as a common sense, proBDNF would be expected to promote Schwann cell
migration. However, we found, in the present study, that exogenous proBDNF also
inhibited in vitro collective migration and chemotaxis of RSC 96 cells, a
spontaneously immortalized rat Schwann cell line. Moreover, proBDNF suppressed
adhesion and spreading of those cells. At molecular level, proBDNF inhibits F
actin polymerization and focal adhesion dynamics in cultured RSC 96 cells.
Therefore, our results suggested a special case against the classical opinion of
"the yin and yang of neurotrophin action" and implied that proBDNF might modulate
peripheral nerve development or regeneration and spinal cord repair through
perturbing native or transplanted Schwann cell migration.
PMID- 27503313
TI - Volar locking plate vs epibloc system for distal radius fractures in the elderly.
AB - PURPOSE: To compare clinical outcomes of ORIF with volar locking plates and the
Epibloc system (ES) in the treatment of distal radius fractures (DRFs) in
patients aged over 65 years. METHODS: We retrospectively examined a consecutive
series of 100 patients with intra-articular or extra-articular DRF who were
admitted to our Department of Orthopaedics and Traumatology between January 2007
and January 2013. Fifty patients were treated using the Epibloc System; and the
other 50 patients using ORIF with volar locking plates. In all patients,
functional evaluation (wrist range of motion [ROM], grip strength and Disability
of the Arm, Shoulder and Hand [DASH] Score) and radiographic assessment (radial
inclination, volar tilt, ulnar variance and articular congruity) were performed
at 2 and 6 weeks, and 3, 6 and 12 months postoperatively; then every 12 months
thereafter. RESULTS: ORIF with volar locking plates was associated with better
outcome than ES in the intra-articular and extra-articular DRF groups, generating
higher average ROM, DASH and visual analogue scale (VAS) scores. Grip strength
mean values, however, were quantified over the minimum level for a functional
wrist (>60%) in both groups. There were no differences between the two techniques
in X-ray parameters, and no further correlation was found with functional outcome
and ROM. CONCLUSIONS: In a low-functioning patient with multiple medical
comorbidities, minimally-invasive surgery with the ES is a safe option, enables
early mobilisation of the wrist and is likely to produce acceptable clinical
outcomes.
PMID- 27503314
TI - Complications in proximal humeral fractures.
AB - Necrosis of the humeral head, infections and non-unions are among the most
dangerous and difficult-to-treat complications of proximal humeral fractures. The
aim of this work was to analyse in detail non-unions and post-traumatic bone
defects and to suggest an algorithm of care. Treatment options are based not only
on the radiological frame, but also according to a detailed analysis of the
patient, who is classified using a risk factor analysis. This method enables the
surgeon to choose the most suitable treatment for the patient, thereby
facilitating return of function in the shortest possible time. The treatment of
such serious complications requires the surgeon to be knowledgeable about the
following possible solutions: increased mechanical stability; biological
stimulation; and reconstructive techniques in two steps, with application of
biotechnologies and prosthetic substitution.
PMID- 27503315
TI - Retrievable inferior vena cava filters in geriatric trauma: Is there an age bias?
AB - BACKGROUND: Trauma patients are at increased risk for developing venous
thromboembolic (VTE) disease. The EAST (Eastern Association for the Surgery of
Trauma) practice management guidelines identified risk factors for VTE, as well
as indications for prophylactic inferior vena cava filters (IVCF). In a 2009
study, our institution found a 26% retrieval rate for IVCF. Lack of retrieval was
most consistently due to lack of follow-up. Our study is a follow-up analysis for
retrieval rate of IVCF, since the formation of a geriatric trauma service. We
anticipated that geriatric trauma patients would have a lower rate of IVCF
retrieval compared to the general trauma patient. METHODS: Our study population
consisted of trauma patients admitted from January 2008 to August 2013, with
documented VTE or high risk for VTE with contraindication to anticoagulation.
INCLUSION CRITERIA: IVCF placed in trauma patients. EXCLUSION CRITERIA: permanent
filters, retrievable filters placed permanently, non-trauma patients, superior
vena cava filters and patients who died before discharge. RESULTS: During the
study period, 160 trauma patients had an IVCF placed, of which 147 survived and
were discharged. Of those patients, 66% (97/147) were planned for retrieval.
Overall, the retrieval rate was 34% (33/97). Following age categorization, rates
were 47% (30/64) and 9% (3/33) for those <65 and >/=65 years old, respectively.
Applying Fisher's Exact Test to a crosstab of planned retrieval by age category
yielded a statistically significant difference, p<0.0005 at alpha=0.05. In the
geriatric population with IVCFs not retrieved, 23% (7/30) died and 67% (20/30)
were lost to follow-up. CONCLUSION: IVCF plays a critical role in the management
of trauma patients with VTE, particularly the geriatric population. Since our
2009 study, we have improved nearly ten percentage points (26% to 34%); however,
we exposed an age bias with retrieval rate being lower in patients >/=65 compared
to those <65 (9% vs. 47%).
PMID- 27503316
TI - Allograft-prosthetic composite versus megaprosthesis in the proximal tibia-What
works best?
AB - Modular megaprosthesis (MP) and allograft-prosthetic composite (APC) are the most
commonly used reconstructions for large bone defects of the proximal tibia. The
primary objective of this study was to compare the two different techniques in
terms of failures and functional results. A total of 42 consecutive patients with
a mean age of 39.6 years (range 15-81 years) who underwent a reconstruction of
the proximal tibia between 2001 and 2012 were included. Twenty-three patients
were given an MP, and 19 patients received an APC. There were nine reconstruction
failures after an average follow-up of 62 months: five in the MP group and four
in the APC group (p=0.957). The 10-year implant survival rate was 78.8% for the
MP and 93.7% for the APC (p=0.224). There were no relevant differences between
the two groups in functional results. Both MP and APC are valid and satisfactory
reconstructive options for massive bone defects in the proximal tibia. In high
demanding patients with no further risk factors, an APC should be considered to
provide the best possible functional result for the extensor mechanism.
PMID- 27503317
TI - Lumbrokinase attenuates myocardial ischemia-reperfusion injury by inhibiting TLR4
signaling.
AB - Lumbrokinase, a novel antithrombotic agent, purified from the earthworm Lumbricus
rubellus, has been clinically used to treat stroke and cardiovascular diseases.
However, inflammatory responses associated with the cardioprotective effect of
lumbrokinase remain unknown. In this study, the signaling pathways involved in
lumbrokinase-inhibited expressions of inflammation mediators were investigated in
rats subjected to myocardial ischemia-reperfusion (I-R) injury. The left main
coronary artery of anesthetized rats was subjected to 1h occlusion and 3h
reperfusion. The animals were treated with/without lumbrokinase and the
severities of I-R-induced arrhythmias and infarction were compared. Lumbrokinase
inhibited I-R-induced arrhythmias and reduced mortality, as well as decreased the
lactate dehydrogenase levels in carotid blood. Lumbrokinase also inhibited the
enhancement of I-R induced expressions of cyclooxygenase (COX)-2, inducible
nitric oxide synthase (iNOS), and matrix metalloproteinase (MMP)-9 through toll
like receptor 4 (TLR4) signaling pathway. Moreover, our results demonstrated that
stimulation with lumbrokinase decreases the phosphorylation of JNK, IkappaB, and
NF-kappaB. These findings suggested that lumbrokinase is a potent
cardioprotective drug in rats with I-R injury. The cardioprotective effects of
lumbrokinase may be correlated with its inhibitory effect on the I-R-induced
expressions of COX-2, iNOS and MMP-9, mediated by TLR4 signaling through JNK and
NF-kappaB pathways.
PMID- 27503318
TI - HCG-mediated activation of mTORC1 signaling plays a crucial role in
steroidogenesis in human granulosa lutein cells.
AB - Luteinizing hormone/human chorionic gonadotropin stimulates progesterone
biosynthesis in the corpus luteum by activating cyclic adenosine
monophosphate/protein kinase A cascade. Recent studies have shown that cyclic
adenosine monophosphate-mediated activation of protein kinase A interacts with
the mammalian target of rapamycin signaling pathways. Furthermore, the use of
mammalian target of rapamycin inhibitors for immunosuppression in transplant
patients has shown adverse effects in reproductive functions. This study examined
whether the mammalian target of rapamycin pathway plays any role in luteinizing
hormone-mediated regulation of progesterone production. Human granulosa lutein
cells were isolated from follicular aspirates of women undergoing in vitro
fertilization. Cells were cultured for 72 h and treated with human chorionic
gonadotropin (50 ng/ml) for different time periods with or without pretreatment
with mammalian target of rapamycin complex 1 inhibitor, rapamycin, (20 nM) for 1
h. Expression of steroidogenic enzymes, including steroidogenic acute regulatory
protein, cholesterol side chain cleavage enzyme, and 3beta-hydroxysteroid
dehydrogenase type 1 messenger RNA, were examined by real-time polymerase chain
reaction after 6 h of human chorionic gonadotropin treatment. Expressions of
phospho-ribosomal protein S6 kinase and cholesterol side chain cleavage enzyme
were analyzed after 15 min and 24 h of human chorionic gonadotropin treatment,
respectively. Progesterone production was analyzed by an enzyme immunoassay kit
after human chorionic gonadotropin (50 ng/ml) or forskolin (10 MUM) treatment for
24 h. Treatment with human chorionic gonadotropin increased the expression of
downstream targets of mammalian target of rapamycin complex 1, as well as
cholesterol side chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1
and steroidogenic acute regulatory protein messenger RNAs. These increases were
inhibited by rapamycin pretreatment. Increased progesterone production in
response to treatment with human chorionic gonadotropin or forskolin was also
blocked by rapamycin pretreatment. Our findings support a role for mammalian
target of rapamycin complex 1 in regulating steroidogenesis in human granulosa
lutein cells.
PMID- 27503319
TI - Transient modulation of calcium and parathyroid hormone stimulates bone
formation.
AB - Intermittent administration of parathyroid hormone can stimulate bone formation.
Parathyroid hormone is a natural hormone that responds to serum calcium levels.
In this study, we examined whether a transient increase and/or decrease in the
serum calcium can stimulate bone formation. Using a mathematical model previously
developed, we first predicted the effects of administration of parathyroid
hormone, neutralizing parathyroid hormone antibody, calcium, and EGTA (calcium
chelator) on the serum concentration of parathyroid hormone and calcium. The
model predicted that intermittent injection of parathyroid hormone and ethylene
glycol tetraacetic acid transiently elevated the serum parathyroid hormone, while
that of parathyroid hormone antibody and calcium transiently reduced parathyroid
hormone in the serum. In vitro analysis revealed that parathyroid hormone's
transient changes (both up and down) elevated activating transcription factor 4
mediated osteocalcin expression. In the mouse model of osteoporosis, both
intermittent administration of calcium and ethylene glycol tetraacetic acid
showed tendency to increase bone mineral density of the upper limb (ulna and
humerus) and spine, but the effects varied in a region-specific manner.
Collectively, the study herein supports a common bone response to administration
of calcium and its chelator through their effects on parathyroid hormone.
PMID- 27503320
TI - Serum anti-mullerian hormone and all-cause mortality in men.
AB - Several studies have examined an association of anti-mullerian hormone to various
risk factors for mortality, however, to the best of our knowledge, no study has
reported a direct relationship between anti-mullerian hormone and all-cause
mortality. Therefore, we examined the relationship between baseline anti
mullerian hormone levels and subsequent all-cause mortality in men during median
follow-up of 9.4 (range = 0-13) years. We used the continuous National Health and
Nutrition Examination Surveys from 1999-2004 combined with National Death Index
for vital status information through December 2011. Cox proportional hazard
models were fit to estimate hazard ratios for all-cause mortality. Models were
adjusted for age, ethnic background, body mass index, hypertension, diabetes,
smoking status, c-reactive protein, total cholesterol, estimated glomerular
filtration rate, serum estradiol, testosterone, sex hormone binding globulin, and
androstenedione. Of the 989 men, 30 % were older than 65 years, 51 % were
Caucasians, 33 % had hypertension, 27 % were active smokers, and 11 % had
diabetes. Mean serum anti-mullerian hormone level of the population was 7.2 (6.3)
ng/mL. During the 8943 person-years of follow-up, 164 (17 %) men died. In
unadjusted analysis, each unit increase in serum anti-mullerian hormone level was
associated with a 13 % lower risk of death (HR = 0.87; 95 %CI = 0.83-0.92). In
multivariable models, the inverse association between serum anti-mullerian
hormone levels and mortality remained significant (HR = 0.94; 95 %CI = 0.90-0.98)
and was independent of confounding variables. Similarly, individuals in the
highest quartile had significantly lower risk of death as compared to individuals
in the lowest quartile (unadjusted HR = 0.13, 95 %CI = 0.07-0.25; adjusted HR =
0.36, 95 %CI = 0.16-0.81). We found an independent and inverse association
between serum anti-mullerian hormone levels and all-cause mortality in men. The
mechanism underlying this association is unknown. Further studies are needed to
validate our findings in men and to examine this association in women.
PMID- 27503322
TI - Structure elucidation of a new cycloartane triterpene glycoside from Souliea
vaginata by NMR.
PMID- 27503321
TI - Effect Of combining FK506 and neurotrophins on neurite branching and elongation.
AB - INTRODUCTION: There is a clinical need to improve the outcomes of peripheral
nerve regeneration and repair after injury. In addition to its immunosuppressive
effects, FK506 (tacrolimus) has been shown to have neuroregenerative properties.
To determine biologically relevant local FK506 and growth factor concentrations,
we performed an in vitro bioassay using dorsal root ganglion (DRG) from chicken
embryos. METHODS: Neurite elongation and neurite branching were analyzed
microscopically after addition of FK506, glial cell line-derived neurotrophic
factor (GDNF), and nerve growth factor (NGF), each alone and in combination.
RESULTS: FK506 induced modest neurite elongation (~500-800 um) without improving
neurite branching significantly. The combination of FK506 with NGF, GDNF, or
both, exerted a potentiating or competitive effect on neurite elongation (~700
1100 um) based on dosage and competitive effect on neurite branching (~0.2-0.4).
CONCLUSIONS: These results strongly suggest that the interaction of FK506 with
GDNF and NGF mediates distinct enhancement of neurite growth. Muscle Nerve 55:
570-581, 2017.
PMID- 27503323
TI - Takotsubo Syndrome as a Cause of False Acute Abdomen in the Early Postoperative
Period After Bariatric Surgery-a Report of Two Cases.
AB - Takotsubo syndrome, also known as broken-heart syndrome, stress-induced
cardiomyopathy or transient apical ballooning syndrome, is a transient disorder
characterized by segmental left ventricular failure in the absence of obstructive
coronary artery disease. Most cases of Takotsubo syndrome are caused by acute
stress that leads to a sudden, temporary weakening of the cardiac musculature.
This stress triggers a rise in circulating catecholamine levels that results in
acute ventricular dysfunction. In this report, we describe two cases of Takotsubo
syndrome in the early postoperative period after bariatric surgery.
PMID- 27503324
TI - Predictors of Intimate Partner Homicide in a Sample of Portuguese Male Domestic
Offenders.
AB - Intimate partner homicide (IPH) is a major social problem, and it is important to
determine the predictors of this violent behavior. The purpose of this study was
to examine the differences between intimate partner violence (IPV) and IPH and to
identify the variables that predict IPH. The sample was composed of 35
perpetrators of IPH, who were compared with 137 perpetrators of IPV. The data
were collected using the Spousal Abuse Risk Assessment. The data suggest that IPH
presents different dynamics from IPV. Being older, exhibiting suicidal and/or
homicidal ideation/intent, and the use of weapons and/or credible threats of
death substantially increase a man's risk of committing IPH. Inversely, not being
single, violating conditional release, and being victimized in childhood decrease
the likelihood of committing IPH. These findings reinforce the assumption that
IPV and IPH have both commonalities and differences and challenge the view that
IPV and IPH are different phenomena and that intimate partner murder is an
inexplicable event. Implications for preventing IPV and IPH are discussed.
PMID- 27503325
TI - Wireless Participant Incentives Using Reloadable Bank Cards to Increase Clinical
Trial Retention With Abused Women Drinkers: A Natural Experiment.
AB - Retaining participants in longitudinal studies is a unique methodological
challenge in many areas of investigation, and specifically for researchers aiming
to identify effective interventions for women experiencing intimate partner
violence (IPV). Individuals in abusive relationships are often transient and have
logistical, confidentiality, and safety concerns that limit future contact. A
natural experiment occurred during a large randomized clinical trial enrolling
women in abusive relationships who were also heavy drinkers, which allowed for
the comparison of two incentive methods to promote longitudinal retention: cash
payment versus reloadable wireless bank cards. In all, 600 patients were enrolled
in the overall trial, which aimed to incentivize participants using a reloadable
bank card system to promote the completion of 11 weekly interactive voice
response system (IVRS) phone surveys and 3-, 6-, and 12-month follow-up phone or
in person interviews. The first 145 participants were paid with cash as a result
of logistical delays in setting up the bank card system. At 12 weeks,
participants receiving the bank card incentive completed significantly more IVRS
phone surveys, odds ratio (OR) = 2.4, 95% confidence interval (CI) = [0.01,
1.69]. There were no significant differences between the two groups related to
satisfaction or safety and/or privacy. The bank card system delivered lower
administrative burden for tracking payments for study staff. Based on these and
other results, our large medical research university is implementing reloadable
bank card as the preferred method of participant incentive payments.
PMID- 27503327
TI - Effect of Sampling Frequency for Real-Time Tablet Coating Monitoring Using Near
Infrared Spectroscopy.
AB - While the sampling of pharmaceutical products typically follows well-defined
protocols, the parameterization of spectroscopic methods and their associated
sampling frequency is not standard. Whereas, for blending, the sampling frequency
is limited by the nature of the process, in other processes, such as tablet film
coating, practitioners must determine the best approach to collecting spectral
data. The present article studied how sampling practices affected the
interpretation of the results provided by a near-infrared spectroscopy method for
the monitoring of tablet moisture and coating weight gain during a pan-coating
experiment. Several coating runs were monitored with different sampling
frequencies (with or without co-adds (also known as sub-samples)) and with
spectral averaging corresponding to processing cycles (1 to 15 pan rotations).
Beyond integrating the sensor into the equipment, the present work demonstrated
that it is necessary to have a good sense of the underlying phenomena that have
the potential to affect the quality of the signal. The effects of co-adds and
averaging was significant with respect to the quality of the spectral data.
However, the type of output obtained from a sampling method dictated the type of
information that one can gain on the dynamics of a process. Thus, different
sampling frequencies may be needed at different stages of process development.
PMID- 27503326
TI - Inhibition of ADAM10 promotes the clearance of Abeta across the BBB by reducing
LRP1 ectodomain shedding.
AB - BACKGROUND: Transport across the blood-brain barrier (BBB) is an important
mediator of beta-amyloid (Abeta) accumulation in the brain and a contributing
factor in the pathogenesis of Alzheimer's disease (AD). One of the receptors
responsible for the transport of Abeta in the BBB is the low density lipoprotein
receptor-related protein 1 (LRP1). LRP1 is susceptible to proteolytic shedding at
the cell surface, which prevents endocytic transport of ligands. Previously, we
reported a strong inverse correlation between LRP1 shedding in the brain and
Abeta transit across the BBB. Several proteases contribute to the ectodomain
shedding of LRP1 including the alpha-secretase, a desintegrin and
metalloproteinase domain containing protein 10 (ADAM10). METHODS: The role of
ADAM10 in the shedding of LRP1 and Abeta BBB clearance was assessed through
pharmacological inhibition of ADAM10 in an in vitro model of the BBB and through
the use of ADAM10 endothelial specific knock-out mice. In addition, an acute
treatment paradigm with an ADAM10 inhibitor was also tested in an AD mouse model
to assess the effect of ADAM10 inhibition on LRP1 shedding and Abetabrain
accumulation. RESULTS: In the current studies, inhibition of ADAM10 reduced LRP1
shedding in brain endothelial cultures and increased Abeta42 transit across an in
vitro model of the BBB. Similarly, transgenic ADAM10 endothelial knockout mice
displayed lower LRP1 shedding in the brain and significantly enhanced Abeta
clearance across the BBB compared to wild-type animals. Acute treatment with the
ADAM10-selective inhibitor GI254023X in an AD mouse model substantially reduced
brain LRP1 shedding and increased Abeta40 levels in the plasma, indicating
enhanced Abeta transit from the brain to the periphery. Furthermore, both soluble
and insoluble Abeta40 and Abeta42 brain levels were decreased following GI254023X
treatment, but these effects lacked statistical significance. CONCLUSIONS: These
studies demonstrate a role for ADAM10 in the ectodomain shedding of LRP1 in the
brain and the clearance of Abeta across the BBB, which may provide a novel
strategy for attenuating Abeta accumulation in the AD brain.
PMID- 27503329
TI - Intrapancreatic Accessory Spleen Mimicking Pancreatic neoplasm.
PMID- 27503328
TI - District health manager and mid-level provider perceptions of practice
environments in acute obstetric settings in Tanzania: a mixed-method study.
AB - BACKGROUND: In sub-Saharan Africa, the capacity of human resources for health
(HRH) managers to create positive practice environments that enable motivated,
productive, and high-performing HRH is weak. We implemented a unique approach to
examining HRH management practices by comparing perspectives offered by mid-level
providers (MLPs) of emergency obstetric care (EmOC) in Tanzania to those
presented by local health authorities, known as council health management teams
(CHMTs). METHODS: This study was guided by the basic strategic human resources
management (SHRM) component model. A convergent mixed-method design was utilized
to assess qualitative and quantitative data from the Health Systems Strengthening
for Equity: The Power and Potential of Mid-Level Providers project. Survey data
was obtained from 837 mid-level providers, 83 of whom participated in a critical
incident interview whose aim was to elicit negative events in the practice
environment that induced intention to leave their job. HRH management practices
were assessed quantitatively in 48 districts with 37 members of CHMTs
participating in semi-structured interviews. RESULTS: The eight human resources
management practices enumerated in the basic SHRM component model were
implemented unevenly. On the one hand, members of CHMTs and mid-level providers
agreed that there were severe shortages of health workers, deficient salaries,
and an overwhelming workload. On the other hand, members of CHMTs and mid-level
providers differed in their perspectives on rewards and allocation of
opportunities for in-service training. Although written standards of performance
and supervision requirements were available in most districts, they did not
reflect actual duties. Members of CHMTs reported high levels of autonomy in key
HRH management practices, but mid-level providers disputed the degree to which
the real situation on the ground was factored into job-related decision-making by
CHMTs. CONCLUSIONS: The incongruence in perspectives offered by members of CHMTs
and mid-level providers points to deficient HRH management practices, which
contribute to poor practice environments in acute obstetric settings in Tanzania.
Our findings indicate that members of CHMTs require additional support to
adequately fulfill their HRH management role. Further research conducted in low
income countries is necessary to determine the appropriate package of
interventions required to strengthen the capacity of members of CHMTs.
PMID- 27503331
TI - Migrated Biliary Stent Causing Entero-enteric Fistula.
PMID- 27503330
TI - A Novel Nomogram to Predict the Prognosis of Patients Undergoing Liver Resection
for Neuroendocrine Liver Metastasis: an Analysis of the Italian Neuroendocrine
Liver Metastasis Database.
AB - Even though surgery remains the only potentially curative option for patients
with neuroendocrine liver metastases, the factors determining a patient's
prognosis following hepatectomy are poorly understood. Using a multicentric
database including patients who underwent hepatectomy for NELMs at seven tertiary
referral hepato-biliary-pancreatic centers between January 1990 and December
2014, we sought to identify the predictors of survival and develop a clinical
tool to predict patient's prognosis after liver resection for NELMs. The median
age of the 238 patients included in the study was 61.9 years (interquartile range
51.5-70.1) and 55.9 % (n = 133) of patients were men. The number of NELMs (hazard
ratio = 1.05), tumor size (HR = 1.01), and Ki-67 index (HR = 1.07) were the
predictors of overall survival. These variables were used to develop a nomogram
able to predict survival. According to the predicted 5-year OS, patients were
divided into three different risk classes: 19.3, 55.5, and 25.2 % of patients
were in low (>80 % predicted 5-year OS), medium (40-80 % predicted 5-year OS),
and high (<40 % predicted 5-year OS) risk classes. The 10-year OS was 97.0, 55.9,
and 20.0 % in the low, medium, and high-risk classes, respectively (p < 0.001).
We developed a novel nomogram that accurately (c-index >70 %) staged and
predicted the prognosis of patients undergoing liver resection for NELMs.
PMID- 27503332
TI - Primary Castleman's Disease of the Liver.
AB - Castleman's disease is a rare lymphoproliferative disorder that may affect the
liver as part of mutlicentric disease or, rarely, as unicentric hepatic disease.
Primary hepatic disease is difficult to diagnose but demonstrates diffusion
restriction on magnetic resonance scan and can be treated curatively with hepatic
resection.
PMID- 27503333
TI - Williamsia herbipolensis sp. nov., isolated from the phyllosphere of Arabidopsis
thaliana.
AB - A Gram-stain-positive, non-endospore-forming actinobacterium (ARP1T) was isolated
from the phyllosphere of Arabidopsis thaliana. On the basis of 16S rRNA gene
sequence phylogeny strain ARP1T was placed into the genus Williamsia and the
closest related species were Williamsia phyllosphaerae (98.5 % 16S rRNA gene
sequence similarity), Williamsia deligens (98.5 %), Williamsia maris (98.3 %) and
Williamsia serinedens (98.2 %). Genome-based comparison indicated a clear
distinction to the type strains of those species with pairwise average nucleotide
identities (ANI) between 76.4-78.4 %. The quinone system of strain ARP1T
consisted predominantly of menaquinones MK-9(H2), MK-7(H2) and MK-8(H2), and the
polar lipid profile contained the major compound diphosphatidylglycerol, and
moderate amounts of phosphatidylethanolamine, phosphatidylglycerol and numerous
unidentified lipids. Mycolic acids were present. These chemotaxonomic traits and
the major fatty acids, which were C16 : 1omega7c, C16 : 0, C18 : 0, C18 :
1omega9c and tuberculostearic acid supported the affiliation of strain ARP1T to
the genus Williamsia. Genotypic, physiological and biochemical testing revealed
clear differences of strain ARP1T to the most closely related species of the
genus Williamsia. Therefore strain ARP1T represents a novel species of this
genus, for which the name Williamsia herbipolensis sp. nov. is proposed. The type
strain is ARP1T (=DSM 46872T=LMG 28679T).
PMID- 27503334
TI - Hyperandrogenism rule no longer in play at Rio Olympics.
PMID- 27503335
TI - Improved hybrid de novo genome assembly of domesticated apple (Malus x
domestica).
AB - BACKGROUND: Domesticated apple (Malus * domestica Borkh) is a popular temperate
fruit with high nutrient levels and diverse flavors. In 2012, global apple
production accounted for at least one tenth of all harvested fruits. A high
quality apple genome assembly is crucial for the selection and breeding of new
cultivars. Currently, a single reference genome is available for apple, assembled
from 16.9 * genome coverage short reads via Sanger and 454 sequencing
technologies. Although a useful resource, this assembly covers only ~89 % of the
non-repetitive portion of the genome, and has a relatively short (16.7 kb) contig
N50 length. These downsides make it difficult to apply this reference in
transcriptive or whole-genome re-sequencing analyses. FINDINGS: Here we present
an improved hybrid de novo genomic assembly of apple (Golden Delicious), which
was obtained from 76 Gb (~102 * genome coverage) Illumina HiSeq data and 21.7 Gb
(~29 * genome coverage) PacBio data. The final draft genome is approximately
632.4 Mb, representing ~ 90 % of the estimated genome. The contig N50 size is
111,619 bp, representing a 7 fold improvement. Further annotation analyses
predicted 53,922 protein-coding genes and 2,765 non-coding RNA genes.
CONCLUSIONS: The new apple genome assembly will serve as a valuable resource for
investigating complex apple traits at the genomic level. It is not only suitable
for genome editing and gene cloning, but also for RNA-seq and whole-genome re
sequencing studies.
PMID- 27503336
TI - Deformable Self-Propelled Micro-Object Comprising Underwater Oil Droplets.
AB - The self-propelled motion with deformation of micrometer-sized soft matter in
water has potential application not only for underwater carriers or probes in
very narrow spaces but also for understanding cell locomotion in terms of non
equilibrium physics. As far as we know, there have been no reports about
micrometer-sized self-propelled soft matter mimicking amoeboid motion underwater.
Here, we report an artificial molecular system of underwater oil droplets
exhibiting self-propelled motion with deformation as an initial experimental
model. We describe the heterogeneity in a deformable self-propelled oil droplet
system in aqueous and oil phases and at their interface based on the behavior and
interaction of surfactant and oil molecules. The current results have great
importance for scientific frontiers such as developing deformable micro-swimmers
and exploring the emergence of self-locomotion of oil droplet-type protocells.
PMID- 27503337
TI - Using willingness-to-pay to establish patient preferences for cancer testing in
primary care.
AB - BACKGROUND: Shared decision making is a stated aim of several healthcare systems.
In the area of cancer, patients' views have informed policy on screening and
treatment but there is little information about their views on diagnostic testing
in relation to symptom severity. METHODS: We used the technique of willingness-to
pay to determine public preferences around diagnostic testing for colorectal,
lung, and pancreatic cancer in primary care in the UK. Participants were
approached in general practice waiting rooms and asked to complete a two-stage
electronic survey that described symptoms of cancer, the likelihood that the
symptoms indicate cancer, and information about the appropriate diagnostic test.
Part 1 asked for a binary response (yes/no) as to whether they would choose to
have a test if it were offered. Part 2 elicited willingness-to-pay values of the
tests using a payment scale followed by a bidding exercise, with the aim that
these values would provide a strength of preference not detectable using the
binary approach. RESULTS: A large majority of participants chose to be tested for
all cancers, with only colonoscopy (colorectal cancer) demonstrating a risk
gradient. In the willingness-to-pay exercise participants placed a lower value on
an X-ray (lung cancer) than the tests for colorectal or pancreatic cancer and X
ray was the only test where risk was clearly related to the willingness-to-pay
value. CONCLUSION: Willingness-to-pay values did not enhance the binary responses
in the way intended; participants appeared to be motivated differently when
responding to the two parts of the questionnaire. More work is needed to
understand how participants perceive risk in this context and how they respond to
questions about willingness-to-pay. Qualitative methods could provide useful
insights.
PMID- 27503338
TI - Re-emergence of H3N2 strains carrying potential neutralizing mutations at the N
linked glycosylation site at the hemagglutinin head, post the 2009 H1N1 pandemic.
AB - BACKGROUND: Seasonally prevalent H1N1 and H3N2 influenza A viruses have evolved
by antigenic drift; this evolution has resulted in the acquisition of asparagine
(N)-linked glycosylation sites (NGSs) in the globular head of hemagglutinin (HA),
thereby affecting the antigenic and receptor-binding properties, as well as
virulence. An epidemiological survey indicated that although the traditional
seasonal H1N1 strain had disappeared, H3N2 became predominant again in the
seasons (2010-11 and 2011-12) immediately following the H1N1 pandemic of 2009.
Interestingly, although the 2009 pandemic H1N1 strain (H1N1pdm09) lacks
additional NGSs, clinically isolated H3N2 strains obtained during these seasons
gained N (Asn) residues at positions 45 and 144 of HA that forms additional NGSs.
METHODS: To investigate whether these NGSs are associated with re-emergence of
H3N2 within the subtype, we tested the effect of amino acid substitutions on
neutralizing activity by using the antisera raised against H3N2 strains with or
without additional NGSs. Furthermore, because the N residue at position 144 of HA
was identified as the site of mismatch between the vaccine and epidemic strains
of 2011-2012, we generated mutant viruses by reverse genetics and tested the
functional importance of this particular NGS for antibody-mediated neutralization
by intranasal inoculation of mice. RESULTS: The results indicated that amino acid
substitution at residue 144 significantly affected neutralization activity,
acting as an escape mutation. CONCLUSIONS: Our data suggest that the newly
acquired NGSs in the HA globular head may play an important role in the re
emergence of endemic seasonal H3N2 strain by aiding the escape from humoral
immunity.
PMID- 27503339
TI - Transapical aortic valve implantation in patients with pre-existing mitral valve
prostheses: a case report.
AB - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has proven to be a
valid option for patients with severe aortic stenosis who are at high
perioperative risk, particularly in patients with previous cardiac surgery.
Several patients with previous mitral valve surgery were reported to have been
successfully treated with TAVI. CASE PRESENTATION: Two patients, one with
mechanical and one with biological mitral valve prosthesis, presented with
symptomatic severe aortic stenosis. After discussion among our multidisciplinary
heart team transapical approach and a JenaValveTM prosthesis was used for TAVI.
Main reasons were to decrease the perioperative risk, avoid a re-opening of the
chest via median sternotomy, and discuss the possible superiority of the
JenaValveTM device due to its design. The patients were successfully treated and
discharged on the 11th and 14th post-operative day, respectively.
Echocardiographic follow up before discharge and up to 2.8 years post-operatively
showed excellent results. CONCLUSIONS: In conclusion, TAVI in patients with
preexisting mitral prostheses-mechanical or biological-is feasible, safe, and
effective and offers a valid alternative to conventional aortic valve replacement
in this particular re-operation scenario. The JenaValveTM device does not
interact with the mitral prosthesis and offers therefore due to its unique design
a potential advantage.
PMID- 27503340
TI - Precise Tuning of Facile One-Pot Gelatin Methacryloyl (GelMA) Synthesis.
AB - Gelatin-methacryloyl (GelMA) is one of the most commonly used photopolymerizable
biomaterials in bio-applications. However, GelMA synthesis remains suboptimal, as
its reaction parameters have not been fully investigated. The goal of this study
is to establish an optimal route for effective and controllable GelMA synthesis
by systematically examining reaction parameters including carbonate-bicarbonate
(CB) buffer molarity, initial pH adjustment, MAA concentration, gelatin
concentration, reaction temperature, and reaction time. We employed several
analytical techniques in order to determine the degree of substitution (DS) and
conducted detailed structural analysis of the synthesized polymer. The results
enabled us to optimize GelMA synthesis, showing the optimal conditions to balance
the deprotonation of amino groups with minimizing MAA hydrolysis, which led to
nearly complete substitution. The optimized conditions (low feed ratio of MAA to
gelatin (0.1 mL/g), 0.25 M CB buffer at pH 9, and a gelatin concentration of 10
20%) enable a simplified reaction scheme that produces GelMA with high
substitution with just one-step addition of MAA in one pot. Looking forward,
these optimal conditions not only enable facile one-pot GelMA synthesis but can
also guide researchers to explore the efficient, high methacrylation of other
biomacromolecules.
PMID- 27503341
TI - BMC Ecology Image Competition 2016: the winning images.
AB - The 2016 BMC Ecology Image Competition marked another celebration of the
astounding biodiversity, natural beauty, and biological interactions documented
by talented ecologists worldwide. For our fourth annual competition, we welcomed
guest judge Dr. Matthew Palmer of Columbia University, who chose the winning
image from over 140 entries. In this editorial, we highlight the award winning
images along with a selection of highly commended honorable mentions.
PMID- 27503342
TI - Renal denervation and hypertension - The need to investigate unintended effects
and neural control of the human kidney.
AB - Increased renal sympathetic nerve activity (RSNA) is present in human and
experimental forms of arterial hypertension. Experimental denervation studies
showed that renal nerves contribute to the development of hypertension. Clinical
trials provided equivocal results on the antihypertensive efficacy of renal
denervation in patients spurring discussions on technical aspects of renal
denervation and further research on the role of renal nerves for the regulation
of kidney function as well as the pathophysiology of hypertension. This review
summarizes recent findings on adrenoceptor expression and function in the human
kidney, adrenoceptor-dependent regulation of sodium chloride transport in the
distal nephron, experimental data on chronic RSNA and the development of high
arterial pressure and consequences of renal denervation that may limit its
antihypertensive efficacy. Future research needs to reduce the gap between our
knowledge on neural control of renal function in animals vs. humans to facilitate
translation of experimental animal data to humans. More experimental studies on
the temporal relationship between RSNA and arterial pressure in the chronic
setting are needed to better define the pathogenetic role of heightened RSNA in
different forms of arterial hypertension in order to improve the rational basis
for renal denervation in antihypertensive therapy. Finally, research on
unintended consequences of renal denervation including but not limited to
reinnervation and denervation supersensitivity needs to be intensified to further
assess the potential of renal denervation to slow the progression of renal
disease and hypertension.
PMID- 27503344
TI - Evaluating the carotid bodies and renal nerves as therapeutic targets for
hypertension.
AB - Despite the plethora of current treatment options, hypertension remains a
difficult condition to adequately control, and there is a pressing need for novel
therapeutic strategies. The carotid body has recently become the focus of
considerable interest as a potential novel treatment target in essential
hypertension. Herein, we appraise the current literature suggesting that the
carotid body plays an important causative role to generate sympathetic
overactivity and drive increases in arterial pressure, in animal models of
hypertension. We also review evidence from human studies showing cardiovascular
benefits to the transient inactivation, or surgical removal of carotid bodies,
and evaluate the potential benefits of pre-screening to identify patients likely
to respond to carotid body-targeted therapy. Finally, given that a high
proportion of patients who have undergone renal nerve ablation procedures remain
hypertensive, we examine whether the renal nerves are necessary for the drop in
blood pressure seen with carotid body removal.
PMID- 27503343
TI - Predictors of autonomic neuropathy in rheumatoid arthritis.
AB - OBJECTIVE: Autonomic dysfunction occurs in rheumatoid arthritis (RA). However,
the association between the autonomic dysfunction and inflammation has not been
investigated in RA. We investigated the relationship between inflammation and ANS
function in RA. METHODS: In this cross-sectional study, 25 RA patients and 25 age
and sex-matched healthy controls were recruited. Autonomic function assessed by
five cardiovascular reflex tests according to Ewing. Parasympathetic dysfunction
established by applying three tests: heart rate response to deep breath (HRD) and
standing (HRS) and Valsalva tests. Sympathetic dysfunction examined by applying
two tests: BP response to standing and handgrip test. Peripheral sympathetic
autonomic function assessed by Sudoscan through measurement of electrochemical
skin conductance of hands and feet. Sudoscan investigates the sweat gland
activity and used as a surrogate to study the damage of sympathetic sudomotor
nerves in neuropathy. It is an indirect assessment tool of sudomotor function.
Disease-specific and inflammatory measures (DAS 28, ESR, CRP, TNF-alpha, IL-6 and
IL-1) were determined. RESULTS: RA patients had significantly impaired HRD, HRS,
BP response to hand grip and sudomotor function as compared to healthy controls.
Pro-inflammatory cytokines were significantly higher in RA as compared to healthy
controls (p<0.05). DAS 28 significantly correlated with HRD in RA. ESR
significantly correlated with HRD and HRS. TNF-alpha significantly correlated
with HRD, HRS, BP response to standing and sudomotor function. Significant
correlation was found between IL-6 and HRS. Seropositive patients had more
pronounced CAN and sudomotor dysfunction. CONCLUSION: Autonomic dysfunction in RA
is related to disease activity, seropositivity and pro-inflammatory cytokines.
PMID- 27503345
TI - Both low and high serum ferritin levels predict mortality risk in hemodialysis
patients without inflammation.
AB - BACKGROUND: Serum ferritin concentration >100 ng/mL was associated with a higher
risk of death in hemodialysis patients in Japan, whereas such an association was
less clear in hemodialysis patients in Western countries. Since Japanese dialysis
patients are generally less inflamed than those in Western countries,
inflammation may modify the association between serum ferritin and the adverse
outcomes. METHODS: We performed an observational cohort study using data from
2606 Japanese hemodialysis patients who participated in the Dialysis Outcomes and
Practice Patterns Study (DOPPS) III (2005-2008) or DOPPS IV (2009-2012). The
predictor was serum ferritin category (<50, 50-99.9, 100-199.9, and >=200 ng/mL),
and the primary and secondary outcomes were all-cause mortality and
cardiovascular hospitalization, respectively. C-reactive protein (CRP, cut-off by
0.3 mg/dL) and serum albumin (cut-off by 3.8 g/dL) were stratification factors
related to systemic inflammation. RESULTS: After adjustment for relevant
confounding factors, a U-shaped association was observed between serum ferritin
and all-cause mortality in the group with low CRP levels, whereas such
relationship was not significant in the high CRP counterparts. In contrast, we
found a linear association between serum ferritin and cardiovascular
hospitalization in the low CRP and high CRP groups commonly. Similar results were
obtained when the total cohort was stratified by serum albumin. CONCLUSIONS:
Serum ferritin showed different patterns of association with all-cause mortality
in hemodialysis patients with versus without inflammation, whereas its
association with cardiovascular hospitalization was similar regardless of
inflammatory conditions.
PMID- 27503346
TI - Resting-state functional connectivity by independent component analysis-based
markers corresponds to areas of initial seizure propagation established by prior
modalities from the hypothalamus.
AB - OBJECTIVE: The aims of this study were to evaluate a clinically practical
functional connectivity protocol designed to blindly identify the corresponding
areas of initial seizure propagation and also to differentiate these areas from
remote secondary areas affected by seizure. The patients in this cohort had
intractable epilepsy caused by intrahypothalamic hamartoma, which is the location
of the ictal focus. The ictal propagation pathway is homogeneous and established,
thus creating the optimum situation for the proposed method validation study.
METHODS: Twelve patients with seizures from hypothalamic hamartoma and 6 normal
control patients underwent resting state functional MRI, using independent
component analysis to identify network differences in patients. This was followed
by seed-based connectivity measures to determine the extent of functional
connectivity derangement between hypothalamus and these areas. The areas with
significant change in connectivity were compared with the results of prior
studies' modalities used to evaluate seizure propagation. RESULTS: The left
amygdala-parahippocampal gyrus area, cingulate gyrus, and occipito-temporal gyrus
demonstrated the highest derangement in connectivity with the hypothalamus, p <
0.01, corresponding to the initial seizure propagation areas established by prior
modalities. Areas of secondary ictal propagation were differentiated from these
initial locations by first being identified as an abnormal neuronal signal source
via independent component analysis, but did not show significant connectivity
directly with the known ictal focus. CONCLUSION: Non-invasive connectivity
measures correspond to areas of initial ictal propagation and differentiate such
areas from secondary ictal propagation, which may aid in ictal focus surgical
disconnection planning and support the use of this newer modality for adjunctive
information in epilepsy surgery evaluation.
PMID- 27503347
TI - Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in
experimental NMO/SD.
AB - Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease
of the central nervous system (CNS). In the majority of patients, it is
associated with the presence of pathogenic serum autoantibodies (the so-called
NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the
formation of large, astrocyte-destructive lesions in spinal cord and optic
nerves. A large number of recent studies using optical coherence tomography (OCT)
demonstrated that damage to optic nerves in NMO/SD is also associated with
retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and
microcystic inner nuclear layer abnormalities. These studies concluded that
retinal injury in NMO/SD patients results from secondary neurodegeneration
triggered by optic neuritis.However, the eye also contains cells expressing AQP4,
i.e., Muller cells and astrocytes in the retina, epithelial cells of the ciliary
body, and epithelial cells of the iris, which raised the question whether the eye
can also be a primary target in NMO/SD. Here, we addressed this point in
experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285
specific T cells and NMO-IgG.We show that these animals show retinitis and
subsequent dysfunction/damage of retinal axons and neurons, and that this
pathology occurs independently of the action of NMO-IgG. We further show that in
the retinae of ENMO animals Muller cell side branches lose AQP4 reactivity, while
retinal astrocytes and Muller cell processes in the RNFL/ganglionic cell layers
are spared. These changes only occur in the presence of both AQP4268-285-specific
T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can
be a primary event in NMO/SD.
PMID- 27503348
TI - Molecular epidemiology of J-subgroup avian leukosis virus isolated from meat-type
chickens in southern China between 2013 and 2014.
AB - Members of avian leukosis virus subgroup J (ALV-J) cause various diseases
associated with tumor formation and decreased fertility, resulting in major
economic losses in the poultry industry worldwide. To assess the status of ALV-J
infection in meat-type chickens in southern China, the molecular epidemiology of
ALV-J strains was investigated. A total of 265 clinical samples collected from
southern China from 2013 to 2014 were investigated in this study for the presence
of ALV-J, which resulted in 12 virus isolates. Phylogenetic analysis showed that
91.7 % (11/12) of the ALV-J isolates have possessed high homology to Chinese
layer isolates and belong to one subgroup. One of the ALV isolates (designated
GD1411-1) was relatively closely related to the ALV-J broiler isolates,
indicating that the GD1411-1 isolate might be a transition strain. Several unique
nucleotide substitutions in gp85 and the U3 region were detected in all 12 ALV-J
isolates. This study provides some interesting information on the molecular
characterization of ALV-J isolates. These findings will be beneficial for
understanding of the pathogenic mechanism of ALV-J infection.
PMID- 27503349
TI - Reasons for Trying E-cigarettes and Risk of Continued Use.
AB - BACKGROUND: Longitudinal research is needed to identify predictors of continued
electronic cigarette (e-cigarette) use among youth. We expected that certain
reasons for first trying e-cigarettes would predict continued use over time (eg,
good flavors, friends use), whereas other reasons would not predict continued use
(eg, curiosity). METHODS: Longitudinal surveys from middle and high school
students from fall 2013 (wave 1) and spring 2014 (wave 2) were used to examine
reasons for trying e-cigarettes as predictors of continued e-cigarette use over
time. Ever e-cigarette users (n = 340) at wave 1 were categorized into those
using or not using e-cigarettes at wave 2. Among those who continued using e
cigarettes, reasons for trying e-cigarettes were examined as predictors of use
frequency, measured as the number of days using e-cigarettes in the past 30 days
at wave 2. Covariates included age, sex, race, and smoking of traditional
cigarettes. RESULTS: Several reasons for first trying e-cigarettes predicted
continued use, including low cost, the ability to use e-cigarettes anywhere, and
to quit smoking regular cigarettes. Trying e-cigarettes because of low cost also
predicted more days of e-cigarette use at wave 2. Being younger or a current
smoker of traditional cigarettes also predicted continued use and more frequent
use over time. CONCLUSIONS: Regulatory strategies such as increasing cost or
prohibiting e-cigarette use in certain places may be important for preventing
continued use in youth. In addition, interventions targeting current cigarette
smokers and younger students may also be needed.
PMID- 27503350
TI - Pneumococcal Vaccines in Preterm Infants: Are More Doses Better? Implications for
Other Vaccines.
PMID- 27503351
TI - Schedules for Pneumococcal Vaccination of Preterm Infants: An RCT.
AB - BACKGROUND AND OBJECTIVE: Premature infants have a higher risk of invasive
pneumococcal disease and are more likely to have lower vaccine responses compared
with term infants. Increasingly, immunization schedules are including a reduced,
2-dose, pneumococcal conjugate vaccine priming schedule. Our goal was to assess
the immunogenicity of 3 commonly used 13-valent pneumococcal conjugate vaccine
(PCV13) priming schedules in premature infants and their response to a 12-month
booster dose. METHODS: Premature infants (<35 weeks' gestation) were randomized
to receive PCV13 at 2 and 4 months (reduced schedule); 2, 3, and 4 months
(accelerated schedule); or 2, 4, and 6 months (extended schedule). All infants
received a 12-month PCV13 booster. Serotype-specific pneumococcal immunoglobulin
G (IgG) for PCV13 serotypes was measured by using enzyme-linked immunosorbent
assay 1 month after the primary and booster vaccinations. RESULTS: A total of 210
infants (median birth gestation, 29(+6) weeks; range, 23(+2)-34(+6) weeks) were
included. After the primary vaccination, 75% (95% confidence interval [CI], 62
85), 88% (95% CI, 76-95), and 97% (95% CI, 87-99) of participants had protective
antibody concentrations for at least one-half the PCV13 serotypes for the
reduced, accelerated, and extended schedules, respectively. After the booster
vaccination, participants receiving the extended schedule had significantly lower
(P < .05) geometric mean concentrations compared with reduced (for 9 of 13
serotypes) and accelerated (for 4 of 13 serotypes) schedules, but nearly all
participations, regardless of schedule or serotype, had seroprotective IgG
concentrations. CONCLUSIONS: A reduced priming schedule of PCV13 resulted in
higher post-booster IgG concentrations but lower post-primary concentrations. The
optimum vaccine schedule for preterm infants will therefore depend on when they
are most at risk for invasive pneumococcal disease.
PMID- 27503352
TI - Studying the Evolution of the Vertebrate Circadian Clock: The Power of Fish as
Comparative Models.
AB - The utility of any model species cannot be judged solely in terms of the tools
and approaches it provides for genetic analysis. A fundamental consideration is
also how its biology has been shaped by the environment and the ecological niche
which it occupies. By comparing different species occupying very different
habitats we can learn how molecular and cellular mechanisms change during
evolution in order to optimally adapt to their environment. Such knowledge is as
important as understanding how these mechanisms work. This is illustrated by the
use of fish models for studying the function and evolution of the circadian
clock. In this review we outline our current understanding of how fish clocks
sense and respond to light and explain how this differs fundamentally from the
situation with mammalian clocks. In addition, we present results from comparative
studies involving two species of blind cavefish, Astyanax mexicanus and
Phreatichthys andruzzii. This work reveals the consequences of evolution in
perpetual darkness for the circadian clock and its regulation by light as well as
for other mechanisms such as DNA repair, sleep, and metabolism which directly or
indirectly are affected by regular exposure to sunlight. Major differences in the
cave habitats inhabited by these two cavefish species have a clear impact on
shaping the molecular and cellular adaptations to life in complete darkness.
PMID- 27503353
TI - Genomic and Transcriptomic Approaches to Study Cancer in Small Aquarium Fish
Models.
AB - Zebrafish and medaka that develop tumors have become valuable tools for
experimental cancer research. With the advent of microarrays and new sequencing
technologies it has become feasible to perform whole genome, exome, and
transcriptome analyses in these fish models. Analyses that compare the two fish
models with each other and with data from human tumors have revealed a plethora
of important insights. An unexpected high degree of comparability of molecular
features of fish and human tumors has been detected. Furthermore, analyses of the
fish model data have uncovered molecules that have not received appropriate
attention in studies on their human tumor counterparts and thus have provided
valuable candidates for novel biomarkers and therapeutic targets.
PMID- 27503354
TI - Gal4 Driver Transgenic Zebrafish: Powerful Tools to Study Developmental Biology,
Organogenesis, and Neuroscience.
AB - Targeted expression by the Gal4-UAS system is a powerful genetic method to
analyze the functions of genes and cells in vivo. Although the Gal4-UAS system
has been extensively used in genetic studies in Drosophila, it had not been
applied to genetic studies in vertebrates until the mid-2000s. This was mainly
due to the lack of an efficient transgenesis tool in model vertebrates, such as
the P-transposable element of Drosophila, that can create hundreds or thousands
of transgene insertions in different loci on the genome and thereby enables the
generation of transgenic lines expressing Gal4 in various tissues and cells via
enhancer trapping. This situation was revolutionized when a highly efficient
transgenesis method using the Tol2 transposable element was developed in the
model vertebrate zebrafish. By using the Tol2 transposon system, we and other
labs successfully performed gene trap and enhancer trap screens in combination
with the Gal4-UAS system. To date, numerous transgenic fish lines that express
engineered versions of Gal4 in specific cells, organs, and tissues have been
generated and used for various aspects of biological studies. By constructing
transgenic fish lines harboring genes of interest downstream of UAS, the Gal4
expressing cells and tissues in those transgenic fish have been visualized and
manipulated via the Gal4-UAS system. In this review, we describe how the Gal4-UAS
system works in zebrafish and how transgenic zebrafish that express Gal4 in
specific cells, tissues, and organs have been used for the study of developmental
biology, organogenesis, and neuroscience.
PMID- 27503355
TI - Whole-Organism Cellular Pathology: A Systems Approach to Phenomics.
AB - Phenotype is defined as the state of an organism resulting from interactions
between genes, environment, disease, molecular mechanisms, and chance. The
purpose of the emerging field of phenomics is to systematically determine and
measure phenotypes across biology for the sake of understanding. Phenotypes can
affect more than one cell type and life stage, so ideal phenotyping would include
the state of every cell type within the context of both tissue architecture and
the whole organism at each life stage. In medicine, high-resolution anatomic
assessment of phenotype is obtained from histology. Histology's interpretative
power, codified by Virchow as cellular pathology, is derived from its ability to
discern diagnostic and characteristic cellular changes in diseased tissues.
Cellular pathology is observed in every major human disease and relies on the
ability of histology to detect cellular change in any cell type due to unbiased
pan-cellular staining, even in optically opaque tissues. Our laboratory has shown
that histology is far more sensitive than stereomicroscopy for detecting
phenotypes in zebrafish mutants. Those studies have also shown that more complete
sampling, greater consistency in sample orientation, and the inclusion of
phenotypes extending over longer length scales would provide greater coverage of
common phenotypes. We are developing technical approaches to achieve an ideal
detection of cellular pathology using an improved form of X-ray microtomography
that retains the strengths and addresses the weaknesses of histology as a
screening tool. We are using zebrafish as a vertebrate model based on the
overlaps between zebrafish and mammalian tissue architecture, and a body size
small enough to allow whole-organism, volumetric imaging at cellular resolution.
Automation of whole-organism phenotyping would greatly increase the value of
phenomics. Potential societal benefits would include reduction in the cost of
drug development, a reduction in the incidence of unexpected severe drug and
environmental toxicity, and more rapid elucidation of the contributions of genes
and the environment to phenotypes, including the validation of candidate disease
alleles identified in population and personal genetics.
PMID- 27503356
TI - Evolutionary Genetics of the Cavefish Astyanax mexicanus.
AB - Blind and depigmented fish belonging to the species Astyanax mexicanus are
outstanding models for evolutionary genetics. During their evolution in the
darkness of caves, they have undergone a number of changes at the morphological,
physiological, and behavioral levels, but they can still breed with their river
dwelling conspecifics. The fertile hybrids between these two morphotypes allow
forward genetic approaches, from the search of quantitative trait loci to the
identification of the mutations underlying the evolution of troglomorphism. We
review here the past 30years of evolutionary genetics on Astyanax: from the first
crosses and the discovery of convergent evolution of different Astyanax cavefish
populations to the most recent evolutionary transcriptomics and genomics studies
that have provided researchers with potential candidate genes to be tested using
functional genetic approaches. Although significant progress has been made and
some genes have been identified, cavefish have not yet fully revealed the secret
of their adaptation to the absence of light. In particular, the genetic
determinism of their loss of eyes seems complex and still puzzles researchers. We
also discuss future research directions, including searches for the origin of
cave alleles and searches for selection genome-wide, as well as the necessary but
missing information on the timing of cave colonization by surface fish.
PMID- 27503357
TI - Transcriptional Regulation During Zygotic Genome Activation in Zebrafish and
Other Anamniote Embryos.
AB - Embryo development commences with the fusion of two terminally differentiated
haploid gametes into the totipotent fertilized egg, which through a series of
major cellular and molecular transitions generate a pluripotent cell mass. The
activation of the zygotic genome occurs during the so-called maternal to zygotic
transition and prepares the embryo for zygotic takeover from maternal factors, in
the control of the development of cellular lineages during differentiation.
Recent advances in next generation sequencing technologies have allowed the
dissection of the genomic and epigenomic processes mediating this transition.
These processes include reorganization of the chromatin structure to a
transcriptionally permissive state, changes in composition and function of
structural and regulatory DNA-binding proteins, and changeover of the
transcriptome as it is overhauled from that deposited by the mother in the oocyte
to a zygotically transcribed complement. Zygotic genome activation in zebrafish
occurs 10 cell cycles after fertilization and provides an ideal experimental
platform for elucidating the temporal sequence and dynamics of establishment of a
transcriptionally active chromatin state and helps in identifying the
determinants of transcription activation at polymerase II transcribed gene
promoters. The relatively large number of pluripotent cells generated by the fast
cell divisions before zygotic transcription provides sufficient biomass for next
generation sequencing technology approaches to establish the temporal dynamics of
events and suggest causative relationship between them. However, genomic and
genetic technologies need to be improved further to capture the earliest events
in development, where cell number is a limiting factor. These technologies need
to be complemented with precise, inducible genetic interference studies using the
latest genome editing tools to reveal the function of candidate determinants and
to confirm the predictions made by classic embryological tools and genome-wide
assays. In this review we summarize recent advances in the characterization of
epigenetic regulation, transcription control, and gene promoter function during
zygotic genome activation and how they fit with old models for the mechanisms of
the maternal to zygotic transition. This review will focus on the zebrafish
embryo but draw comparisons with other vertebrate model systems and refer to
invertebrate models where informative.
PMID- 27503358
TI - The Zebrafish as Model for Deciphering the Regulatory Architecture of Vertebrate
Genomes.
AB - Despite enormous progress to map cis-regulatory modules (CRMs), like enhancers
and promoters in genomes, elucidation of the regulatory landscape of the
developing embryo remains a challenge. The zebrafish embryo with its experimental
virtues has a great potential to contribute to this endeavor. However, so far
progress remained behind expectation. We discuss here available methods and their
limitations and how the zebrafish embryo could contribute in the future to
unravel the wiring of the vertebrate genome.
PMID- 27503359
TI - Transcriptomic Approaches in the Zebrafish Model for Tuberculosis-Insights Into
Host- and Pathogen-specific Determinants of the Innate Immune Response.
AB - Mycobacterium marinum infection in zebrafish has become a well-established model
of tuberculosis. Both embryonic and adult zebrafish infection studies have
contributed to our knowledge of the development and function of tuberculous
granulomas, which are typical of mycobacterial pathogenesis. In this review we
discuss how transcriptome profiling studies have helped to characterize this
infection process. We illustrate this using new RNA sequencing (RNA-Seq) data
that reveals three main phases in the host response to M. marinum during the
early stages of granuloma development in zebrafish embryos and larvae. The early
phase shows induction of complement and transcription factors, followed by a
relatively minor induction of pro-inflammatory cytokines within hours following
phagocytosis of M. marinum. A minimal response is observed in the mid-phase,
between 6 hours and 1day post infection, when the tissue dissemination of M.
marinum begins. During subsequent larval development the granulomas expand and a
late-phase response is apparent, which is characterized by progressively
increasing induction of complement, transcription factors, pro-inflammatory
cytokines, matrix metalloproteinases, and other defense and inflammation-related
gene groups. This late-phase response shares common components with the strong
and acute host transcriptome response that has previously been reported for
Salmonella typhimurium infection in zebrafish embryos. In contrast, the early/mid
phase response to M. marinum infection, characterized by suppressed pro
inflammatory signaling, is strikingly different from the acute response to S.
typhimurium infection. Furthermore, M. marinum infection shows a collective and
strongly fluctuating regulation of lipoproteins, while S. typhimurium infection
has pronounced effects on amino acid metabolism and glycolysis.
PMID- 27503360
TI - Peripheral biomarkers of stroke: Focus on circulatory microRNAs.
AB - Stroke is the second leading cause of death in the world. Stroke occurs when
blood flow stops, and that stoppage results in reduced oxygen supply to neurons
in the brain. The occurrence of stroke increases with age, but anyone at any age
can suffer from stroke. Recent research has implicated multiple cellular changes
in stroke patients, including oxidative stress and mitochondrial dysfunction,
inflammatory responses, and changes in mRNA and proteins. Recent research has
also revealed that stroke is associated with modifiable and non-modifiable risk
factors. Stroke can be controlled by modifiable risk factors, including diet,
cardiovascular, hypertension, smoking, diabetes, obesity, metabolic syndrome,
depression and traumatic brain injury. Stroke is the major risk factor for
vascular dementia (VaD) and Alzheimer's disease (AD). The purpose of this article
is to review the latest developments in research efforts directed at identifying
1) latest developments in identifying biomarkers in peripheral and central
nervous system tissues, 2) changes in microRNAs (miRNAs) in patients with stroke,
3) miRNA profile and function in animal brain, and 4) protein biomarkers in
ischemic stroke. This article also reviews research investigating circulatory
miRNAs as peripheral biomarkers of stroke.
PMID- 27503361
TI - Effects of Simple and Microencapsulated Lactobacillus acidophilus With or Without
Inulin on the Broiler Meat Quality Infected by Avian Influenza Virus (H9N2).
AB - The aims of the present study were to investigate the effects of simple and
microencapsulated Lactobacillus acidophilus as probiotic with or without inulin
as prebiotic on meat quality of broiler infected by avian influenza virus (H9N2).
Two hundred-day-old chicks were randomly allocated into 14 groups based on
simple, microencapsulated probiotic and prebiotic and based on vaccination and
challenge with H9N2 virus. Groups 1-7 contained 20 chicks, and groups 8-12 and 14
contained 10 chicks. Group 13 was derived from group 1 with 10 chicks at
challenge day with avian influenza virus (AIV). Half of the groups were
vaccinated by H9N2 vaccine on day 5. All groups except the negative control and
positive vaccine control were challenged with 106.5 EID50 of low-virulence H9N2
AIV at day 21. Each bird was received 109 CFU of simple or microencapsulated
probiotic on days 0 and 17 by gavage. Prebiotic as dose as 0.1 % of feed weight
was used daily. Increase in water-holding capacity, dry matter, ash and protein
content, and decrease in dripping loss plus beneficial changes in lightness and
redness of breast meat were detected in response to probiotic especially
microencapsulated synbiotic. In conclusion, probiotic alone or with prebiotic was
able to improve the physicochemical properties of chicken breast muscle in both
healthy and AIV-infected chickens.
PMID- 27503362
TI - Enrofloxacin and Probiotic Lactobacilli Influence PepT1 and LEAP-2 mRNA
Expression in Poultry.
AB - Expression of peptide transporter 1 (PepT1) and liver-expressed antimicrobial
peptide 2 (LEAP-2) in chickens can be influenced by food deprivation,
pathological conditions and drug administration. Effect of three putative
probiotic Lactobacillus strains and enrofloxacin on the expression of PepT1 and
LEAP-2 mRNA was investigated in Ross 308 chickens. One-day-old chicks (n = 24)
were allocated to following groups: control (without treatment); group treated
with probiotics via feed; group treated with a combination of probiotics and
enrofloxacin; and a group given enrofloxacin only. The drug was administered at a
dose of 10 mg kg-1, via drinking water for 5 days. Samples from liver, duodenum
and jejunum were collected 126 h after the start of the treatment. Expression
levels of PepT1 and LEAP-2 were determined by real-time polymerase chain reaction
and were statistically evaluated by Mann-Whitney test. Enrofloxacin administered
alone or in combination with probiotics provoked a statistically significant up
regulation of PepT1 mRNA levels in the measured organ sites. These changes can be
attributed to a tendency of improvement in utilization of dietary peptide and in
body weight gain. LEAP-2 mRNA expression levels did not change significantly in
enrofloxacin-treated chickens in comparison with control group.
PMID- 27503363
TI - Genetic mapping of canine fear and aggression.
AB - BACKGROUND: Fear/anxiety and anger/aggression greatly influence health, quality
of life and social interactions. They are a huge burden to wellbeing, and
personal and public economics. However, while much is known about the physiology
and neuroanatomy of such emotions, little is known about their genetics - most
importantly, why some individuals are more susceptible to pathology under stress.
RESULTS: We conducted genomewide association (GWA) mapping of breed stereotypes
for many fear and aggression traits across several hundred dogs from diverse
breeds. We confirmed those findings using GWA in a second cohort of partially
overlapping breeds. Lastly, we used the validated loci to create a model that
effectively predicted fear and aggression stereotypes in a third group of dog
breeds that were not involved in the mapping studies. We found that i) known IGF1
and HMGA2 loci variants for small body size are associated with separation
anxiety, touch-sensitivity, owner directed aggression and dog rivalry; and ii)
two loci, between GNAT3 and CD36 on chr18, and near IGSF1 on chrX, are associated
with several traits, including touch-sensitivity, non-social fear, and fear and
aggression that are directed toward unfamiliar dogs and humans. All four genome
loci are among the most highly evolutionarily-selected in dogs, and each of those
was previously shown to be associated with morphological traits. We propose that
the IGF1 and HMGA2 loci are candidates for identical variation being associated
with both behavior and morphology. In contrast, we show that the GNAT3-CD36 locus
has distinct variants for behavior and morphology. The chrX region is a special
case due to its extensive linkage disequilibrium (LD). Our evidence strongly
suggests that sociability (which we propose is associated with HS6ST2) and
fear/aggression are two distinct GWA loci within this LD block on chrX, but there
is almost perfect LD between the peaks for fear/aggression and animal size.
CONCLUSIONS: We have mapped many canine fear and aggression traits to single
haplotypes at the GNAT3-CD36 and IGSF1 loci. CD36 is widely expressed, but areas
of the amygdala and hypothalamus are among the brain regions with highest
enrichment; and CD36-knockout mice are known to have significantly increased
anxiety and aggression. Both of the other genes have very high tissue-specificity
and are very abundantly expressed in brain regions that comprise the core anatomy
of fear and aggression - the amygdala to hypothalamic-pituitary-adrenal (HPA)
axis. We propose that reduced-fear variants at these loci may have been involved
in the domestication process.
PMID- 27503364
TI - Effect of Low-Furanocoumarin Hybrid Grapefruit Juice Consumption on Midazolam
Pharmacokinetics.
AB - The objectives of this study were to investigate the effect of grapefruit juice
low in furanocoumarins on CYP3A activity and to summarize previous findings of
enzyme inhibition measured by the metabolism of midazolam after intake of
grapefruit juice. Twelve healthy volunteers participated in a prospective,
randomized, double-blinded, 3-way crossover clinical study to determine the
effect of regular grapefruit juice (RGJ) and a novel, low-furanocoumarin hybrid
grapefruit juice (HGJ) on the metabolism of oral midazolam, used as a probe for
in vivo CYP3A activity, compared with water as a control. The RGJ was 100% hand
squeezed "Hudson" grapefruit juice, and the HGJ contained low amounts of
furanocoumarin constituents. The point estimates (90% confidence intervals) for
the RGJ/water midazolam AUC geometric mean ratio was 122% (107-140). The point
estimate for the HGJ/water midazolam AUC ratio was within the 80% to 125%
bioequivalence range, indicating an absence of interaction. This finding also
prompted a systematic review of available evidence on the pharmacokinetic
alteration of midazolam by grapefruit juice. Although most studies demonstrated
alteration in midazolam pharmacokinetics supporting inhibition of CYP3A activity
as a likely mechanism, the cohorts included in these studies and the extent of
the pharmacokinetic interaction varied widely. The current study indicated
grapefruit juice-drug interaction varies substantially based on patient
characteristics and/or grapefruit juice product-related factors, including the
amount of furanocoumarin constituents present in the juice.
PMID- 27503365
TI - Comparison of the Aerosol Stability of 2 Strains of Zaire ebolavirus From the
1976 and 2013 Outbreaks.
AB - The largest outbreak of Ebola virus disease began in Gueckedou, Guinea, West
Africa, in December 2013 and rapidly spread to major population centers in 3 West
African countries. Early reports in some scientific and public media speculated
that the virus had evolved to more effectively transmit between humans. One route
of transmission postulated was aerosol transmission, although there was little
epidemiological evidence to support this claim. This study investigates the
viability of 2 Zaire ebolavirus strains within aerosols at 22 degrees C and 80%
relative humidity over time. The results presented here indicate that there is no
difference in virus stability between the 2 strains and that viable virus can be
recovered from an aerosol 180 minutes after it is generated.
PMID- 27503366
TI - Reply to Lipsitch.
PMID- 27503368
TI - Matsumiya et al (J Infect Dis 2015; 211:1499-509).
PMID- 27503367
TI - Comment on "Gain-of-Function Research and the Relevance to Clinical Practice".
PMID- 27503369
TI - Bhattacharya et al (J Infect Dis 2016; 214:196-204).
PMID- 27503370
TI - Resistance to Increasing Chemical Classes of Fungicides by Virtue of "Selection
by Association" in Botrytis cinerea.
AB - Previous research has shown that Botrytis cinerea isolates with resistance to
multiple chemical classes of fungicides exist in eastern strawberry fields. In
this study, the fungicide resistance profiles of 2,130 isolates from flowers of
commercial strawberry fields located in multiple states was determined over four
consecutive strawberry production seasons. Producers were asked to alternate
single-site fungicides that were considered low risk in their specific location
based on resistance monitoring results in their fields. This recommendation led
to an increase of chemical class diversity used in the spray programs. Results
indicated that simultaneous resistance in individual isolates to two, three,
four, five, six, and seven classes of fungicides increased over time. The
increase in chemical class resistances within isolates was likely due to a
process we termed "selection by association", where fungicide resistance traits
were often linked to the trait being selected rather than the selectable trait
itself. Data analysis also indicated that the odds were highest for isolates
resistant to one chemical class (1CCR) to be resistant to thiophanate-methyl; for
2CCR isolates to be resistant to thiophanate-methyl and pyraclostrobin; and for
3CCR isolates to be resistant to thiophanate-methyl, pyraclostrobin, and either
cyprodinil or fenhexamid. We hypothesize that the more chemical classes are used
in a spray program, the faster isolates will be selected with increasing numbers
of chemical class resistances by virtue of selection by association if such
isolates preexist in the population.
PMID- 27503371
TI - Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.
AB - Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of
wheat globally. Upon infection, the fungus secretes a number of effector
proteins. Although a large repository of putative effectors has been predicted
using bioinformatic pipelines, the lack of available high-throughput effector
screening systems has limited functional studies on these proteins. In this
study, we mined the available transcriptomes of Puccinia graminis and P.
striiformis to look for potential effectors that suppress host hypersensitive
response (HR). Twenty small (<300 amino acids), secreted proteins, with no
predicted functions were selected for the HR suppression assay using Nicotiana
benthamiana, in which each of the proteins were transiently expressed and
evaluated for their ability to suppress HR caused by four cytotoxic effector-R
gene combinations (Cp/Rx, ATR13/RPP13, Rpt2/RPS-2, and GPA/RBP-1) and one mutated
R gene-Pto(Y207D). Nine out of twenty proteins, designated Shr1 to Shr9
(suppressors of hypersensitive response), were found to suppress HR in N.
benthamiana. These effectors varied in the effector-R gene defenses they
suppressed, indicating these pathogens can interfere with a variety of host
defense pathways. In addition to HR suppression, effector Shr7 also suppressed
PAMP-triggered immune response triggered by flg22. Finally, delivery of Shr7
through Pseudomonas fluorescens EtHAn suppressed nonspecific HR induced by
Pseudomonas syringae DC3000 in wheat, confirming its activity in a homologous
system. Overall, this study provides the first evidence for the presence of
effectors in Puccinia species suppressing multiple plant defense responses.
PMID- 27503372
TI - Revisitation of autoimmune hypophysitis: knowledge and uncertainties on
pathophysiological and clinical aspects.
AB - PURPOSE: This publication reviews the accepted knowledges and the findings still
discussed on several features of autoimmune hypophysitis, including the most
recently described forms, such as IgG4 and cancer immunotherapy- related
hypophysitis. METHODS: The most characteristic findings and the pending
controversies were derived from a literature review and previous personal
experiences. A single paragraph focused on some atypical examples of the disease
presenting under confounding pretences. RESULTS: Headache, visual field
alterations and impaired pituitary secretion are the most frequent clinical
findings of the disease. Pituitary biopsy, still considered the gold diagnostic
standard, does not always receive consent from the patients. The role of magnetic
resonance imaging is limited, as this disease may generate images similar to
those of other diseases. The role of antipituitary and antihypothalamus
antibodies is still discussed owing to methodological difficulties and also
because the findings on the true pituitary antigen(s) are still debated. However,
the low sensitivity and specificity of immunofluorescence, one of the more widely
employed methods to detect these antibodies, may be improved, considering a
predetermined cut-off titre and a particular kind of immunostaining. CONCLUSION:
Autoimmune hypophysitis is a multifaceted disease, which may certainly be
diagnosed by pituitary biopsy. However, the possible different clinical,
laboratory and imaging features must be considered by the physician to avoid a
misdiagnosis when examining a possibly affected patient. Therapeutic choice has
to be made taking into account the clinical conditions and the degree of
hypothalamic-pituitary involvement, but also considering that spontaneous
remissions can occur.
PMID- 27503373
TI - An MRI study of white matter tract integrity in regular cannabis users: effects
of cannabis use and age.
AB - RATIONALE: Conflicting evidence exists on the effects of cannabis use on brain
white matter integrity. The extant literature has exclusively focused on younger
cannabis users, with no studies sampling older cannabis users. OBJECTIVES: We
recruited a sample with a broad age range to examine the integrity of major white
matter tracts in association with cannabis use parameters and neurodevelopmental
stage. METHODS: Regular cannabis users (n = 56) and non-users (n = 20) with a
mean age of 32 (range 18-55 years) underwent structural and diffusion MRI scans.
White matter was examined using voxel-based statistics and via probabilistic
tract reconstruction. The integrity of tracts was assessed using average
fractional anisotropy, axial diffusivity and radial diffusivity. Diffusion
measures were compared between users and non-users and as group-by-age
interactions. Correlations between diffusion measures and age of onset, duration,
frequency and dose of current cannabis use were examined. RESULTS: Cannabis users
overall had lower fractional anisotropy than healthy non-users in the forceps
minor tract only (p = .015, partial eta = 0.07), with no voxel-wise differences
observed. Younger users showed predominantly reduced axial diffusivity, whereas
older users had higher radial diffusivity in widespread tracts. Higher axial
diffusivity was associated with duration of cannabis use in the cingulum angular
bundle (beta = 5.00 * 10(-5), p = .003). Isolated higher AD in older cannabis
users was also observed. CONCLUSIONS: The findings suggest that exogenous
cannabinoids alter normal brain maturation, with differing effects at various
neurodevelopmental stages of life. These age-related differences are posited to
account for the disparate results described in the literature.
PMID- 27503375
TI - Erratum to: Psychosis in Parkinson's Disease: Epidemiology, Pathophysiology, and
Management.
PMID- 27503374
TI - The early infant gut microbiome varies in association with a maternal high-fat
diet.
AB - BACKGROUND: Emerging evidence suggests that the in utero environment is not
sterile as once presumed. Work in the mouse demonstrated transmission of
commensal bacteria from mother to fetus during gestation, though it is unclear
what modulates this process. We have previously shown in the nonhuman primate
that, independent of obesity, a maternal high-fat diet during gestation and
lactation persistently shapes the juvenile gut microbiome. We therefore sought to
interrogate in a population-based human longitudinal cohort whether a maternal
high-fat diet similarly alters the neonatal and infant gut microbiome in early
life. METHODS: A representative cohort was prospectively enrolled either in the
early third trimester or intrapartum (n = 163), with a subset consented to
longitudinal sampling through the postpartum interval (n = 81). Multiple body
site samples, including stool and meconium, were collected from neonates at
delivery and by 6 weeks of age. A rapid dietary questionnaire was administered to
estimate intake of fat, added sugars, and fiber over the past month (National
Health and Examination Survey). DNA was extracted from each infant meconium/stool
sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis. RESULTS:
On average, the maternal dietary intake of fat ranged from 14.0 to 55.2 %, with
an average intake of 33.1 % (sigma = 6.1 %). Mothers whose diets significantly
differed from the mean (+/-1 standard deviation) were separated into two distinct
groups, a control group (n = 13, MU = 24.4 %) and a high-fat group (n = 13, MU =
43.1 %). Principal coordinate analysis revealed that the microbiome of the
neonatal stool at birth (meconium) clustered differently by virtue of maternal
gestational diet (PERMANOVA p = 0.001). LEfSe feature selection identified
several taxa that discriminated the groups, with a notable relative depletion of
Bacteroides in the neonates exposed to a maternal high-fat gestational diet
(Student's t-test, p < 0.05) that persisted to 6 weeks of age. CONCLUSIONS:
Similar to the primate, independent of maternal body mass index, a maternal high
fat diet is associated with distinct changes in the neonatal gut microbiome at
birth which persist through 4-6 weeks of age. Our findings underscore the
importance of counseling pregnant mothers on macronutrient consumption during
pregnancy and lactation.
PMID- 27503376
TI - Osteokeratoprosthesis Using Tibial Bone: Surgical Technique and Outcomes.
AB - PURPOSE: To analyze the anatomical and functional results of keratoprosthesis
using tibial bone autograft. METHODS: We reviewed 113 charts of patients who
underwent tibial bone osteokeratoprothesis implantation at the Centro de
Oftalmologia Barraquer. Kaplan-Meier survival curves with 95% confidence interval
were calculated for functional success, defined as best corrected visual acuity
(BCVA) >=0.05 on the decimal scale, and for anatomical success, defined as
retention of the keratoprosthesis lamina. Multivariate analysis was used to test
the impact of clinical factors on anatomical and functional survival rates.
RESULTS: Based on Kaplan-Meier analyses, tibial bone keratoprosthesis 5-year and
10-year anatomical survival rates were 69.5% and 53.5%, respectively. Functional
survival rate at 5 years was 33% and at 10 years was 19.2%. Considering primary
diagnosis, chemical burn had better anatomical and functional survival rates than
autoimmune or infectious diseases. Patient age did not have a significant effect
on keratoprosthesis survival rates. About 48.7% of the patients who underwent
surgery had complications: keratoprosthesis extrusion, glaucoma, retinal
detachment and buccal mucosa necrosis were the most frequent ones. CONCLUSION:
Half of the patients with tibial bone KPro had retained the keratoprosthesis
after 10 years post-surgery and one-fifth of them had visual acuity of 0.05 or
better at the same period. Considering that these patients have no other way to
recover their vision either because they have no canine tooth or their buccal or
dental conditions are not adequate for OOKP, this modified surgery is their only
hope.
PMID- 27503377
TI - Altered expression of chemokines and their receptors at porcine maternal-fetal
interface during early and mid-gestational fetal loss.
AB - Chemokines play a significant role in pregnancy, especially during embryonic
attachment and placental development. During early pregnancy, immune cells are
recruited extensively to the endometrium in several species including pigs.
However, this recruitment is solely mediated by the presence of the conceptus in
pigs making it a unique feature compared with other species (humans, primates and
mice). To understand the biological significance of chemokine expression and
immune cell recruitment in the context of fetal loss, we investigate a well
characterized porcine fetal loss model during the window of early pregnancy at
gestational day (gd) 20 and mid-pregnancy (gd50). These periods coincide with 25
40 % of conceptus loss. Using targeted quantitative polymerase chain reaction and
Western blot approaches, we screened a specific set of chemokines. Comparisons
were made with endometrial lymphocytes (ENDO LY), endometrium and chorioallantoic
membranes (CAM) associated with spontaneously arresting and healthy conceptus
attachment sites (CAS). mRNA expression studies revealed an increased expression
of CXCR3 and CCR5 in ENDO LY and of CXCL10, CXCR3, CCL5 and CCR5 in the
endometrium associated with arresting CAS at gd20. DARC was decreased in the
endometrium at gd50. CCL1 was increased in CAM associated with arresting CAS at
gd50. Some of these differences were also noted at the protein level (CXCL10,
CXCR3, CCL5 and CCR5) in the endometrium and CAM. CD45+ immunohistochemistry
demonstrated a significantly higher localization in ENDO LY in the endometrium
associated with healthy versus arresting counterparts. Most of these differences
were observed in early pregnancy and might contribute towards a shift in immune
cell functions.
PMID- 27503379
TI - Erratum to: The ''abdominal whirlpool'' sign.
PMID- 27503378
TI - MicroRNA-34b/c inhibits aldosterone-induced vascular smooth muscle cell
calcification via a SATB2/Runx2 pathway.
AB - Increasing evidence shows that aldosterone and specific microRNAs (miRs)
contribute to vascular smooth muscle cell (VSMC) calcification. In this study, we
aim to explore the mechanistic links between miR-34b/c and aldosterone in VSMC
calcification. VSMC calcification models were established both in vitro and in
vivo. First, the levels of aldosterone, miR-34b/c and special AT-rich sequence
binding protein 2 (SATB2) were measured. Then, miR-34b/c mimics or inhibitors
were transfected into VSMCs to evaluate the function of miR-34b/c. Luciferase
reporter assays were used to demonstrate whether SATB2 was a direct target of miR
34b/c. Aldosterone and SATB2 were found to be markedly upregulated during VSMC
calcification, whereas miR-34b/c expression was downregulated. Treatment with the
mineralocorticoid receptor (MR) antagonist eplerenone inhibited VSMC
calcification. In aldosterone-induced VSMC calcification, miR-34b/c levels were
downregulated and SATB2 protein was upregulated. Furthermore, miR-34b/c
overexpression alleviated aldosterone-induced VSMC calcification as well as
inhibited the expression of SATB2 protein, whereas miR-34b/c inhibition markedly
enhanced VSMC calcification and upregulated SATB2 protein. In addition,
luciferase reporter assays showed that SATB2 is a direct target of miR-34b/c in
VSMCs. Overexpression of SATB2 induced Runx2 overproduction and VSMC
calcification. Therefore, miR-34b/c participates in aldosterone-induced VSMC
calcification via a SATB2/Runx2 pathway. As miR-34b/c appears to be a negative
regulator, it has potential as a therapeutic target of VSMC calcification.
PMID- 27503380
TI - Contrast media for fluoroscopic examinations of the GI and GU tracts: current
challenges and recommendations.
AB - One of the significant challenges facing radiologists who perform and interpret
studies of the gastrointestinal and genitourinary systems have been periodic
interruptions in the availability of barium and iodinated contrast media
specially formulated for gastrointestinal (GI) and genitourinary (GU) studies.
These interruptions are due to the US Food and Drug Administration's recent
requirement for more stringent documentation of the safety and efficacy of
contrast media and the consolidation among contrast manufacturers. Therefore,
radiologists may be required to recommend an alternative means of evaluation,
such as computed tomography, magnetic resonance, or endoscopy, or they may need
to substitute a different formulation of a contrast agent not specifically
developed for GI or GU use, for example the utilization of an agent designed and
marketed for vascular use. This article reviews the current status of
fluoroscopic contrast media, and provides suggestions and recommendations for the
optimal and alternative use of contrast media formulations.
PMID- 27503381
TI - Iatrogenic, blunt, and penetrating trauma to the biliary tract.
AB - Iatrogenic and traumatic bile leaks are uncommon. However, given the overall
increase in number of hepatobiliary surgeries and the paradigm shift toward
nonoperative management of patients with liver trauma, they have become more
prevalent in recent years. Imaging is essential to establishing early diagnosis
and guiding treatment as the clinical signs and symptoms of bile leaks are
nonspecific, and a delay in recognition of bile leaks portends a high morbidity
and mortality rate. Findings suspicious for a bile leak at computed tomography or
ultrasonography include free or contained peri- or intrahepatic low density fluid
in the setting of recent trauma or hepatobiliary surgery. Hepatobiliary
scintigraphy and magnetic resonance cholangiopancreatography (MRCP) with
hepatobiliary contrast agents can be used to detect active or contained bile
leak. MRCP with hepatobiliary contrast agents has the unique ability to reveal
the exact location of bile leak, which often governs whether endoscopic
management or surgical management is warranted. Percutaneous transhepatic
cholangiography and fluoroscopy via an indwelling catheter that is placed either
percutaneously or surgically are useful modalities to guide percutaneous
transhepatic biliary drain placement which can provide biliary drainage and/or
diversion in the setting of traumatic biliary injury. Surgical treatment of a
bile duct injury with Roux-en-Y hepaticojejunostomy is warranted if definitive
treatment cannot be accomplished through percutaneous or endoscopic means.
PMID- 27503382
TI - Abdominal radiograph pearls and pitfalls for the emergency department
radiologist: a pictorial review.
AB - Abdominal plain films are often the first imaging examination performed on a
patient with abdominal pain in the emergency department. Radiograph findings can
help guide clinical management and the need for advanced imaging. A pictorial
review of a range of abdominal radiograph findings is presented, including bowel
gas patterns, abdominal organ evaluation, pathologic gas, calcifications,
implanted devices, and foreign bodies.
PMID- 27503383
TI - The role of preoperative graded compression ultrasound in detecting acute
appendicitis and influencing the negative appendectomy rate.
AB - PURPOSE: The diagnosis of acute appendicitis is mainly clinical and is correct in
about 80% of patients, but 20-33% present with atypical findings, which resulted
in a negative appendectomy rate of 20-30%. The graded compression ultrasound
method in the diagnosis of acute appendicitis was reported with a sensitivity of
89%, and specificity of 95%. In this study, we aim to evaluate the graded
compression ultrasonography in the diagnosis of acute appendicitis, its influence
on the clinical judgment to operate, and its role in lowering the negative
appendectomy rate. METHODS: 1073 patients treated surgically for acute
appendicitis between January 2005 and December 2014 were reviewed. Ultrasound
findings, histopathological diagnosis, and positive or negative appendectomy
rates were analyzed. RESULTS: 647 (60.3%) patients were males and 426 (39.7%)
females. The mean age was 26.5 years. Positive ultrasound findings were recorded
in 892 (83.13%), while negative findings were recorded in 181 (16.87%). Positive
appendectomy was recorded in 983 (91.6%), while negative appendectomy was
recorded in 90 (8.4%). The sensitivity was 83%, specificity was 100%, and the
rate of negative appendectomy was 8.39%. CONCLUSION: Graded compression technique
of ultrasound is a useful modality, in addition to the clinical judgment of the
surgeon and clinical findings, in detecting true positive cases of acute
appendicitis, and thus reducing the negative appendectomy rate. Values of 100%
specificity, and 8.4% negative appendectomy rate, or better, could be achieved,
when an experienced surgeon and a professional radiologist collaborate in the
diagnosis of acute appendicitis.
PMID- 27503384
TI - Editor's Highlight: Computational Modeling of Plasma Vitellogenin Alterations in
Response to Aromatase Inhibition in Fathead Minnows.
AB - In vertebrates, conversion of testosterone into 17beta-estradiol (E2) is
catalyzed by cytochrome P450 (CYP) 19A aromatase. An important role of E2 in
oviparous vertebrates such as fish is stimulation of hepatic synthesis of the
glycolipoprotein vitellogenin (VTG), an egg yolk precursor essential to oocyte
development and larval survival. In fathead minnows (FHMs) (Pimephales promelas)
exposed to the aromatase inhibitor fadrozole, plasma VTG levels do not change in
concert with plasma E2 levels. Specifically, while plasma VTG and E2 levels both
drop quickly when aromatase is first inhibited, the recovery of plasma VTG upon
cessation of aromatase inhibition is substantially delayed relative to the
recovery of plasma E2. We modified an existing computational model of the FHM
hypothalamic-pituitary-gonadal axis to evaluate alternative hypotheses that might
explain this delay. In the first hypothesis, a feedback loop involving active
transport of VTG from the blood into the ovary is used. The activity of the
transporter is negatively regulated by ovarian VTG. In the second hypothesis, a
type 1 coherent feed-forward loop is implemented in the liver. This loop has 2
arms, both requiring E2 activation. The first arm describes direct, canonical E2
driven transcriptional induction of VTG, and the second describes an E2-driven
intermediate transcriptional regulator that is also required for VTG synthesis.
Both hypotheses accurately described the observed VTG dynamics. This result could
be used to guide design of laboratory experiments intended to determine if either
of the motifs, or perhaps even both of them, actually do control VTG dynamics in
FHMs exposed to aromatase inhibitors.
PMID- 27503385
TI - Editor's Highlight: Development of an In vitro Assay Measuring Uterine-Specific
Estrogenic Responses for Use in Chemical Safety Assessment.
AB - A toxicity pathway approach was taken to develop an in vitro assay using human
uterine epithelial adenocarcinoma (Ishikawa) cells as a replacement for measuring
an in vivo uterotrophic response to estrogens. The Ishikawa cell was determined
to be fit for the purpose of recapitulating in vivo uterine response by verifying
fidelity of the biological pathway components and the dose-response predictions
to women of child-bearing age. Expression of the suite of estrogen receptors that
control uterine proliferation (ERalpha66, ERalpha46, ERalpha36, ERbeta, G-protein
coupled estrogen receptor (GPER)) were confirmed across passages and treatment
conditions. Phenotypic responses to ethinyl estradiol (EE) from transcriptional
activation of ER-mediated genes, to ALP enzyme induction and cellular
proliferation occurred at concentrations consistent with estrogenic activity in
adult women (low picomolar). To confirm utility of this model to predict
concentration-response for uterine proliferation with xenobiotics, we tested the
concentration-response for compounds with known uterine estrogenic activity in
humans and compared the results to assays from the ToxCast and Tox21 suite of
estrogen assays. The Ishikawa proliferation assay was consistent with in vivo
responses and was a more sensitive measure of uterine response. Because this
assay was constructed by first mapping the key molecular events for cellular
response, and then ensuring that the assay incorporated these events, the
resulting cellular assay should be a reliable tool for identifying estrogenic
compounds and may provide improved quantitation of chemical concentration
response for in vitro-based safety assessments.
PMID- 27503386
TI - Editor's Highlight: Interactive Genotoxicity Induced by Environmentally Relevant
Concentrations of Benzo(a)Pyrene Metabolites and Arsenite in Mouse Thymus Cells.
AB - Arsenic and polycyclic aromatic hydrocarbon (PAH) exposures affect many people
worldwide leading to cancer and other diseases. Arsenite (As+3) and certain PAHs
are known to cause genotoxicity. However, there is limited information on the
interactions between As+3 and PAHs at environmentally relevant concentrations.
The thymus is the primary immune organ for T cell development in mammals. Our
previous studies showed that environmentally relevant concentrations of As+3
induce genotoxicity in mouse thymus cells through Poly(ADP-ribose) polymerase
(PARP) inhibition. Certain PAHs, such as the metabolites of benzo(a)pyrene (BaP),
are known to cause DNA damage by forming DNA adducts. In the present study,
primary mouse thymus cells were examined for DNA damage following 18 hr in vitro
treatments with 5 or 50 nM As+3 and 100 nM BaP, benzo[a]pyrene-7,8-dihydrodiol
(BP-Diol), or benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). An interactive
increase in genotoxicity and apoptosis were observed following treatments with 5
nM As + 3 + 100 nM BP-diol and 50 nM As + 3 + 100 nM BPDE. We attribute the
increase in DNA damage to inhibition of PARP inhibition leading to decreased DNA
repair. To further support this hypothesis, we found that a PARP inhibitor, 3,4
dihydro-5[4-(1-piperindinyl) butoxyl]-1(2H)-isoquinoline (DPQ), also interacted
with BP-diol to produce an increase in DNA damage. Interestingly, we also found
that As+3 and BP-diol increased CYP1A1 and CYP1B1 expression, suggesting that
increased PAH metabolism may also contribute to genotoxicity. In summary, these
results show that the suppression of PARP activity and induction of CYP1A1/CYP1B1
may act together to increase DNA damage produced by As+3 and PAHs.
PMID- 27503387
TI - Identification of Drug-Drug Interactions In Vitro: A Case Study Evaluating the
Effects of Sofosbuvir and Amiodarone on hiPSC-Derived Cardiomyocytes.
AB - Drug-drug interactions pose a difficult drug safety problem, given the increasing
number of individuals taking multiple medications and the relative complexity of
assessing the potential for interactions. For example, sofosbuvir-based drug
treatments have significantly advanced care for hepatitis C virus-infected
patients, yet recent reports suggest interactions with amiodarone may cause
severe symptomatic bradycardia and thus limit an otherwise extremely effective
treatment. Here, we evaluated the ability of human induced pluripotent stem cell
derived cardiomyocytes (hiPSC-CMs) to recapitulate the interaction between
sofosbuvir and amiodarone in vitro, and more generally assessed the feasibility
of hiPSC-CMs as a model system for drug-drug interactions. Sofosbuvir alone had
negligible effects on cardiomyocyte electrophysiology, whereas the sofosbuvir
amiodarone combination produced dose-dependent effects beyond that of amiodarone
alone. By comparison, GS-331007, the primary circulating metabolite of
sofosbuvir, had no effect alone or in combination with amiodarone. Further
mechanistic studies revealed that the sofosbuvir-amiodarone combination disrupted
intracellular calcium (Ca2+) handling and cellular electrophysiology at
pharmacologically relevant concentrations, and mechanical activity at supra
pharmacological (30x Cmax) concentrations. These effects were independent of the
common mechanisms of direct ion channel block and P-glycoprotein activity. These
results support hiPSC-CMs as a comprehensive, yet scalable model system for the
identification and evaluation of cardioactive pharmacodynamic drug-drug
interactions.
PMID- 27503388
TI - From the Cover: Exposure to Oral Antibiotics Induces Gut Microbiota Dysbiosis
Associated with Lipid Metabolism Dysfunction and Low-Grade Inflammation in Mice.
AB - Due to a long history of improper and excessive use, Penicillin G (Pen G) and
erythromycin (Ery) are regularly detected in environmental samples and pose a
great threat to human health. Here, we set out to investigate effects of Pen G,
Ery or their mixture on lipid metabolism and gut microbiota in order to better
understand their toxicological mechanisms. Male C57BL/6J mice were exposed either
to 60 MUg/ml Pen G, Ery or a half mixture of both for 6 weeks or to 10 MUg/ml Pen
G, Ery or a half mixture of both for 14 weeks. In a recovery experiment, male
mice were exposed to 60 MUg/ml Pen G or Ery for 2 weeks and then maintained
without antibiotics for up to 8 weeks. It was observed that oral exposure to Pen
G, Ery or their mixture induced lipid metabolism dysfunction, characterized by
significantly increased lipid accumulations, triglycerides (TG) levels and
expression of key genes involved in free fatty acid (FFA) synthesis, FFA
transport and TG synthesis in the liver. In addition, Pen G and Ery exposure
induced an inflammatory response as indicated by the increase of serum
lipopolysaccharide levels and the up-regulation of key genes that regulate immune
responses in the liver, fat, colon and ileum. Moreover, Pen G and Ery exposure
rapidly and dramatically altered the composition of the microbiota in feces and
cecum. Furthermore, high throughput sequencing of V3-V4 region of bacterial 16S
rRNA gene revealed additional significant changes in the cecal microbiota of
antibiotics-treated mice. Importantly, it took a very long time to reconstitute
the normal composition of the gut microbiota after it was imbalanced by
antibiotics exposure. Orally administered Pen G and Ery (especially to the
latter) can induce gut microbiota dysbiosis, which may indirectly link antibiotic
exposure to host metabolic disorders and inflammation.
PMID- 27503389
TI - Geographic Variation in the Cumulative Risk of Imprisonment and Parental
Imprisonment in the United States.
AB - This article reports estimates of the cumulative risk of imprisonment and
parental imprisonment for demographic groups in four regions and four states.
Regional and state-level cumulative risks were markedly higher for African
Americans and Latinos than for whites. African Americans faced the highest
cumulative risks of imprisonment in the Midwest, Northeast, and two southern
states. Latinos were most likely to serve time in state prison in the West, where
their cumulative risk was comparable to that of African Americans. Latino
children had a relatively high risk of having a parent imprisoned in the
Northeast as well. Racial disparities in the cumulative risk of imprisonment and
parental imprisonment did not increase linearly with increases in the cumulative
risk for all groups.
PMID- 27503390
TI - Age Differences in Cognitive and Affective Theory of Mind: Concurrent
Contributions of Neurocognitive Performance, Sex, and Pulse Pressure.
AB - OBJECTIVES: Theory of mind (ToM) allows us to detect and make inferences about
cognitive and affective mental states. Mixed findings exist regarding (a) age
differences in cognitive and affective ToM and (b) what mechanisms may underlie
changes in the two components. We addressed these questions by examining the
unique and joint contributions of neurocognitive performance, pulse pressure
(PP), and biological sex to age differences in cognitive and affective ToM.
METHOD: We tested 86 young and 85 older adults on standardized measures of
neurocognitive performance and ToM. Predictors were derived from demographics
(sex), in-office PP, and measures of executive functions, semantic memory, and
episodic memory. We used path analysis to identify concurrent predictors of
cognitive and affective ToM between groups and invariance analyses to assess age
differences in the relative strength of identified predictors. RESULTS: We
demonstrated robust age differences in cognitive and affective ToM. Certain
neurocognitive predictors of ToM were more salient among older individuals; most
predictors were shared across age groups and equivalent in magnitude. DISCUSSION:
To our knowledge, this study represents the most comprehensive investigation to
date of predictors of ToM in aging. Findings highlight the need for continued
investigation of ToM within a multidimensional framework.
PMID- 27503391
TI - Prevalence and quantification of geographic atrophy associated with newly
diagnosed and treatment-naive exudative age-related macular degeneration.
AB - OBJECTIVE: To identify and quantify geographic atrophy (GA) associated with
neovascular age-related macular degeneration (AMD) at initial presentation using
a fundus autofluorescence (FAF) semi-automated software and to correlate the
results with demographic and clinical data. DESIGN: Retrospective, observational
study. METHODS: The study population consisted of treatment-naive patients with
newly diagnosed neovascular AMD. Best-corrected visual acuity, fundus
photographs, infrared reflectance, FAF and spectral-domain optical coherence
tomography were performed, associated with fluorescein and indocyanine green
angiographies. Identification of GA was independently performed by three readers.
Quantification of atrophy areas was done using RegionFinder Software (RFA), a
semi-automated software embedded in Spectralis device (Heidelberg Engineering,
Germany). RESULTS: We included 206 eyes of 173 consecutive patients (72% female,
mean age: 79.7+/-9.1 years). Type I choroidal neovascularisation (CNV) was
observed in 44.2% of eyes, type II CNV was observed in 20.9% and mixed CNV lesion
was observed in 11.7%. Polypoidal choroidal vasculopathy was diagnosed in 7.7%
and type III CNV was diagnosed in 15.5%. Analysis of FAF frames showed that GA
was associated with nAMD in 46/206 eyes (22.3%). Taking into account data both
from Region Finder and multimodal imaging, our results suggest that GA was
present in 24.3% of eyes newly diagnosed with exudative AMD. Mean size of GA was
1.23+/-1.76 mm2 (range 0.03-7.39). CONCLUSION: GA is associated with nAMD in 1/4
of cases at initial presentation. Combined imaging, including RFA is an effective
tool to identify and quantify GA at diagnosis.
PMID- 27503392
TI - Non-traumatic corneal perforations: aetiology, treatment and outcomes.
AB - PURPOSE: To report aetiology, characteristics, treatment and main outcomes of non
traumatic corneal perforations in a single referral centre. METHODS: A
retrospective review of clinical records of patients diagnosed with non-traumatic
corneal perforation. The analysed data included demographic characteristics,
medical history, initial and final corrected distance visual acuity (CDVA),
perforation aetiology, size, location, initial therapy, surgical treatment,
ocular integrity and complications. A comparison between non-infectious and
infectious groups was performed. Different variables were analysed through a
multiple logistic regression analysis for the probability to have at least one
more procedure. RESULTS: We included 127 eyes of 116 patients with a mean age of
50 years and a mean follow-up of 11 months. The initial CDVA was 3.00 logarithm
of the minimum angle of resolution (logMAR) and the final CDVA was 2.30 logMAR
(p>0.5). Regarding treatment, of the 49 eyes with an initial cyanoacrylate patch,
35 eyes (71.4%) had at least one more procedure performed (p>0.001). In
comparison, of the 49 eyes with an initial tectonic penetrating keratoplasty
(PK), 33 (67.3%) eyes remained stable while 16 (32.7%) eyes needed one or more
interventions (p=0.004). In a multiple logistic regression analysis, an initial
cyanoacrylate patch represented a probability of 4.7 times to require a
subsequent procedure in comparison with an initial PK. Overall, globe integrity
was achieved in 96.1% of the cases. CONCLUSIONS: Corneal perforations represent
an important cause of ocular morbidity. The use of a cyanoacrylate patch is
useful as an initial therapy in corneal perforations; however, procedures such as
PK are often necessary to achieve anatomical success, especially in non
infectious aetiologies.
PMID- 27503393
TI - Repeatability and interobserver reproducibility of a new optical biometer based
on swept-source optical coherence tomography and comparison with IOLMaster.
AB - OBJECTIVE: To evaluate the precision of the measurements in healthy subjects
obtained with a new optical biometer (OA-2000, Tomey, Nagoya, Japan) using swept
source optical coherence tomography (SS-OCT) and compare these measurements with
those provided by the IOLMaster v5.4 (Carl Zeiss Meditec AG, Jena, Germany) using
partial coherence interferometry (PCI). METHODS: Axial length (AL), keratometry
(K) over 2.5 mm and 3.0 mm diameters, anterior chamber depth (ACD) (corneal
epithelium to lens), lens thickness (LT), central corneal thickness and corneal
diameter (CD) were measured with SS-OCT by two experienced operators.
Intraobserver repeatability and interobserver reproducibility were assessed. AL,
ACD, K and CD were also measured with PCI for agreement analysis using Bland
Altman plots. RESULTS: Sixty-five eyes of 65 normal subjects were enrolled in the
prospective study. The SS-OCT measurements revealed high repeatability and
reproducibility with low test-retest repeatability, low within-subject
coefficient of variation (CoV) and high intraclass correlation coefficients.
Bland-Altman analysis showed narrow 95% limits of agreement for most parameters
indicating excellent agreement for AL (-0.05 mm to 0.07 mm), K values both at 2.5
mm (-0.42 D to 0.20 D) and 3.0 mm (-0.42 D to 0.08 D) and ACD (-0.19 mm to 0.22
mm) except for the CD (-1.11 mm to -0.01 mm). CONCLUSIONS: The repeatability and
reproducibility of SS-OCT were excellent for all parameters including AL, K, ACD,
LT and CD values. High agreement was shown between SS-OCT and PCI for most
biometrical parameters.
PMID- 27503394
TI - Impact of initial visual acuity on anti-VEGF treatment outcomes in patients with
macular oedema secondary to retinal vein occlusions in routine clinical practice.
AB - AIM: To determine the impact of initial visual acuity (VA) on anti-vascular
endothelial growth factor (VEGF) treatment outcomes in patients with macular
oedema secondary to retinal vein occlusions in routine clinical practice.
METHODS: A retrospective study was conducted at a single academic institution to
identify 177 treatment naive patients with macular oedema secondary to branch
retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO) and central
retinal vein occlusion (CRVO) treated with intravitreal anti-VEGFs. Exclusion
criteria included prior intravitreal injection or presence of active confounding
ocular disease. Patients were stratified by initial VA; main outcomes measured
were average change in VA and mean absolute change in central subfield thickness
(CST) at 6 and 12 months. RESULTS: Patients with BRVO with initial VA of 20/40 or
better had no significant changes in average letters gained and CST from baseline
(+2.6 letters, p=0.42; -48.94 um, p=0.12) compared with patients with initial VA
between 20/50 and 20/300 (+13.2 letters, p<0.001; -98.20 um, p<0.001) after 12
months. Patients with CRVO/HRVO with initial VA of 20/320 or worse had the most
improvement in average letters gained and CST from baseline (+42.2 letters,
p<0.001; -182.84 um, p=0.004) with anti-VEGF therapy compared with patients with
initial VA between 20/50 and 20/300 (+9.4 letters, p=0.016; -160.87 um, p<0.001)
and patients with initial VA of 20/40 or better (-9.6 letters, p=0.14; -47.92 um,
p=0.38). CONCLUSIONS: For macular oedema secondary to retinal vein occlusion,
anti-VEGF treatment can result in a greater improvement in average letters gained
and in CST for those with poor initial VA compared with those with better initial
VA.
PMID- 27503395
TI - Visual object categorisation in people with glaucoma.
AB - PURPOSE: There is evidence that people with glaucoma exhibit difficulties with
some complex visual tasks such as face recognition, motion perception and scene
exploration. The purpose of this study was to determine whether glaucoma affects
the ability to categorise briefly presented visual objects in central vision.
METHODS: Visual categorisation performance of 14 people with glaucoma (primary
open angle glaucoma and preperimetric) and 15 age-matched controls was measured,
assessing both accuracy and response times. Grey level photographs of objects
(size) were presented for 28 ms foveally. Perimetric thresholds were normal for
all participants within the central 3 degrees . Two levels of contrasts were
included: one medium level at 50% and one with high contrast at 100%. RESULTS: On
average, accuracy was significantly decreased by 7% (p=0.046) for the medium
contrast stimuli in patients with glaucoma (87% of correct response, SD: 5%)
compared with controls (94% of correct response, SD: 4.7%). Group average
response times were significantly slower for the patients relative to the control
group (712 ms, SD: 53 ms compared with 643 ms, SD: 34 ms for the control group;
p<0.01). Performance was equivalent in the two groups when the picture contrast
was 100%. CONCLUSIONS: The impairment observed in the categorisation task
supports previous work that demonstrates that people with glaucoma can have
greater difficulties with complex visual tasks than is predicted by their visual
field loss. The performance was equivalent to age-matched controls when contrast
was maximised.
PMID- 27503396
TI - Optical coherence tomography angiography of type 3 neovascularisation in age
related macular degeneration after antiangiogenic therapy.
AB - BACKGROUND/AIMS: To assess the microvascular response of type 3
neovascularisation secondary to age-related macular degeneration (AMD) after
antivascular endothelial growth factor (anti-VEGF) therapy using optical
coherence tomography angiography (OCTA). METHODS: Consecutive patients diagnosed
with AMD and type 3 neovascularisation based on clinical examination, structural
optical coherence tomography and fluorescein angiography when available were
retrospectively evaluated. En face OCTA imaging (3*3 mm scans) with quantitative
microvascular analysis was performed at baseline and after a single anti-VEGF
intravitreal injection. RESULTS: 17 eyes of 14 patients underwent OCTA before and
after anti-VEGF treatment. OCTA demonstrated significant regression of small
calibre type 3 neovascular tufts in all eyes. Median lesion area was 0.061 mm2
(range 0.003-0.198 mm2) at baseline and 0.009 mm2 (range 0-0.085 mm2, p=0.0003)
at follow-up. Cystoid macular oedema and/or subretinal fluid resolved in all
cases after treatment. The type 3 lesions became undetectable with OCTA post
treatment in 5 of the 17 eyes. However, in 11 eyes, large feeder vessels were
identified and remained unchanged after treatment. CONCLUSIONS: The microvascular
morphology of type 3 neovascularisation secondary to AMD was assessed at baseline
and follow-up and showed significant regression in response to anti-VEGF therapy
by OCTA. Quantitative OCTA analysis was also performed and confirmed remarkable
regression in response to a single intravitreal anti-VEGF injection.
PMID- 27503397
TI - Metrics for monitoring cancer inequities: residential segregation, the Index of
Concentration at the Extremes (ICE), and breast cancer estrogen receptor status
(USA, 1992-2012).
AB - PURPOSE: To address the paucity of evidence on residential segregation and
cancer, we explored their relationship using a new metric: the Index of
Concentration at the Extremes (ICE). We focused on breast cancer estrogen
receptor (ER) status, a biomarker associated with survival and, etiologically,
with social and economic privilege. METHODS: We obtained data from the 13
registry group of US Surveillance, Epidemiology, and End Results (SEER) program
for 1992-2012 on all women aged 25-84 who were diagnosed with primary invasive
breast cancer (n = 516,382). We appended to each case's record her annual county
median household income quintile and the quintile for her annual county value for
ICE measures for income (<=20th vs. >=80th household income quintile),
race/ethnicity (black vs. white), and income plus race/ethnicity (low-income
black vs. high-income white). The odds of being ER+ versus ER- were estimated in
relation to the county-level income and ICE measures, adjusting for relevant
covariates. RESULTS: Women in the most privileged versus deprived county quintile
for household income and for all three ICE measures had a 1.1- to 1.3-fold
increased odds (95 % confidence intervals excluding 1) of having an ER+ tumor.
These results were robust to adjustment for age at diagnosis, cancer registry,
tumor characteristics (tumor stage, size, histology, grade), and race/ethnicity.
CONCLUSION: A focus on segregation offers news possibilities for understanding
how inequitable group relations contribute to cancer inequities. The utility of
employing the ICE for monitoring cancer inequities should be investigated in
relation to other cancer outcomes.
PMID- 27503398
TI - Multicolor Fluorescence Detection-Based Microfluidic Device for Single-Cell
Metabolomics: Simultaneous Quantitation of Multiple Small Molecules in Primary
Liver Cells.
AB - Single-cell metabolomics can be used to study cell diversity and how cells
respond to environment. There is an urgent need to develop effective detection
methods for single-cell metabolomics. Microchip electrophoresis with laser
induced fluorescence detection (MCE-LIFD) is a powerful tool to detect
metabolites at the single-cell level. However, the existing one-laser excitation
and one-color fluorescence collection in MCE-LIFD is not sufficient for the
simultaneous detection of multiple small molecules with wide variations in their
fluorescence excitation and emission spectra. In this manuscript, we describe a
multicolor fluorescence detection-based microfluidic device (MFD-MD) for single
cell metabolomics research. We selected primary liver cells from acute ethanol
stimulated mice as the model cells and hydrogen peroxide (H2O2), glutathione
(GSH), and cysteine (Cys) as representative small-molecule metabolites for single
cell analysis. The microfluidic chip enabled accurate single-cell manipulation
and effective electrophoresis separation. The new multicolor fluorescence
detection permitted simultaneous analysis of H2O2, GSH, and Cys. Ethanol exposure
induced an increase in H2O2 and a decrease in GSH and Cys. Obvious cell
heterogeneity was observed. These results provide insights regarding the
intracellular oxidative/antioxidative molecular mechanism in response to external
stimuli. The MFD-MD provides a new opportunity for simultaneous single-cell
analysis of multiple metabolites.
PMID- 27503399
TI - Heat stroke admissions during heat waves in 1,916 US counties for the period from
1999 to 2010 and their effect modifiers.
AB - BACKGROUND: Heat stroke is a serious heat-related illness, especially among older
adults. However, little is known regarding the spatiotemporal variation of heat
stroke admissions during heat waves and what factors modify the adverse effects.
METHODS: We conducted a large-scale national study among 23.5 million Medicare
fee-for-service beneficiaries per year residing in 1,916 US counties during 1999
2010. Heat wave days, defined as a period of at least two consecutive days with
temperatures exceeding the 97th percentile of that county's temperatures, were
matched to non-heat wave days by county and week. We fitted random-effects
Poisson regression models to estimate the relative risk (RR) of heat stroke
admissions on a heat wave day as compared to a matched non-heat wave day. A
variety of effect modifiers were tested including individual-level covariates,
community-level covariates, meteorological conditions, and the intensity and
duration of the heat wave event. RESULTS: The RR declined substantially from 71.0
(21.3-236.2) in 1999 to 3.5 (1.9-6.5) in 2010, and was highest in the northeast
and lowest in the west north central regions of the US. We found a lower RR among
counties with higher central air conditioning (AC) prevalence. More severe and
longer-lasting heat waves had higher RRs. CONCLUSIONS: Heat stroke
hospitalizations associated with heat waves declined dramatically over time,
indicating increased resilience to extreme heat among older adults. Considerable
risks, however, still remain through 2010, which could be addressed through
public health interventions at a regional scale to further increase central AC
and monitoring heat waves.
PMID- 27503400
TI - Changes of visual-field global indices after cataract surgery in primary open
angle glaucoma patients.
AB - PURPOSE: To determine changes of visual-field (VF) global indices after cataract
surgery and the factors associated with the effect of cataracts on those indices
in primary open-angle glaucoma (POAG) patients. METHODS: A retrospective chart
review of 60 POAG patients who had undergone phacoemulsification and intraocular
lens insertion was conducted. All of the patients were evaluated with standard
automated perimetry (SAP; 30-2 Swedish interactive threshold algorithm; Carl
Zeiss Meditec Inc.) before and after surgery. VF global indices before surgery
were compared with those after surgery. The best-corrected visual acuity,
intraocular pressure (IOP), number of glaucoma medications before surgery, mean
total deviation (TD) values, mean pattern deviation (PD) value, and mean TD-PD
value were also compared with the corresponding postoperative values.
Additionally, postoperative peak IOP and mean IOP were evaluated. Univariate and
multivariate logistic regression analyses were performed to identify the factors
associated with the effect of cataract on global indices. RESULTS: Mean deviation
(MD) after cataract surgery was significantly improved compared with the
preoperative MD. Pattern standard deviation (PSD) and visual-field index (VFI)
after surgery were similar to those before surgery. Also, mean TD and mean TD-PD
were significantly improved after surgery. The posterior subcapsular cataract
(PSC) type showed greater MD changes than did the non-PSC type in both the
univariate and multivariate logistic regression analyses. In the univariate
logistic regression analysis, the preoperative TD-PD value and type of cataract
were associated with MD change. However, in the multivariate logistic regression
analysis, type of cataract was the only associated factor. None of the other
factors was associated with MD change. CONCLUSIONS: MD was significantly affected
by cataracts, whereas PSD and VFI were not. Most notably, the PSC type showed
better MD improvement compared with the non-PSC type after cataract surgery.
Clinicians therefore should carefully analyze VF examination results for POAG
patients with the PSC type.
PMID- 27503401
TI - Changes in ocular higher-order aberrations following botulinum toxin treatment in
patients with blepharospasm : BTX improves dry eye in patients with BEB.
AB - BACKGROUND/AIMS: To evaluate the effects of botulinum toxin type A (BTX-A)
treatment in patients with benign essential blepharospasm (BEB) by monitoring the
ocular surface and ocular higher-order aberrations (HOAs) before and after
treatment. METHODS: The present study reports a prospective case series of 38
patients (76 eyes, 11 men and 27 women; mean age 66.8 +/- 9.8 years) with BEB who
underwent BTX-A treatment at Kokura Memorial Hospital between 2013 and 2014.
Patients were evaluated for ophthalmoscopic findings, Schirmer I test, tear film
break-up time (t-BUT), HOAs, fluctuation index (FI), stability index (SI) using a
wavefront aberrometer, 15 subjective symptoms using the Dry Eye-Related Quality
of Life Score (DEQS), and complications before and after the treatment. RESULTS:
After BTX-A treatment, the Schirmer I test score improved significantly from 5.9
+/- 5.4 to 8.7 +/- 6.1 mm and t-BUT recovered from 5.2 +/- 1.7 to 7.3 +/- 1.7 s.
HOAs were classified into four patterns: stable (60.5 %), small fluctuation (14.5
%), sawtooth (17.1 %), and reverse sawtooth (7.9 %), and they significantly
reduced after the treatment. Only FI (not SI) showed a marked reduction, and the
DEQS significantly improved from 44.7 +/- 21.6 to 37.6 +/- 21.0 after the
treatment (p < 0.05). There were no complications during the observations.
CONCLUSION: BTX-A is a treatment with a high potential to improve ocular surface
disorders induced by BEB.
PMID- 27503402
TI - Protein-like Nanoparticles Based on Orthogonal Self-Assembly of Chimeric
Peptides.
AB - A novel two-component self-assembling chimeric peptide is designed where two
orthogonal protein folding motifs are linked side by side with precisely defined
position relative to one another. The self-assembly is driven by a combination of
symmetry controlled molecular packing, intermolecular interactions, and geometric
constraint to limit the assembly into compact dodecameric protein nanoparticles.
PMID- 27503403
TI - Impaired function of trophoblast cells derived from translocated hESCs may
explain pregnancy loss in women with balanced translocation (11;22).
AB - PURPOSE: The aim of the study was to study whether the trophoblasts carrying
unbalanced translocation 11,22 [t(11;12)] display abnormal expression of
trophoblastic genes and impaired functional properties that may explain
implantation failure. METHODS: t(11;22) hESCs and control hESCs were
differentiated in vitro into trophoblast cells in the presence of BMP4, and
trophoblast vesicles (TBVs) were created in suspension. The expression pattern of
extravillous trophoblast (EVT) genes was compared between translocated and
control TBVs. The functional properties of the TBVs were evaluated by their
attachment to endometrium cells (ECC1) and invasion through trans-well inserts.
RESULTS: TBVs derived from control hESCs expressed EVT genes from functioning
trophoblast cells. In contrast, TBVs differentiated from the translocated hESC
line displayed impaired expression of EVT genes. Moreover, the number of TBVs
that were attached to endometrium cells was significantly lower compared to the
controls. Correspondingly, invasiveness of trophoblast-differentiated
translocated cells was also significantly lower than that of the control cells.
CONCLUSIONS: These results may explain the reason for implantation failure in
couple carriers of t(11;22). They also demonstrate that translocated hESCs
comprise a valuable in vitro human model for studying the mechanisms underlying
implantation failure.
PMID- 27503404
TI - Exenatide treatment increases serum irisin levels in patients with obesity and
newly diagnosed type 2 diabetes.
AB - OBJECTIVE: Irisin is a myokine secreted by skeletal muscle during exercise.
Abnormal serum irisin levels are associated with obesity and type 2 diabetes
(T2D). This study investigated the changes in serum irisin in the obese patients
with newly diagnosed T2D following glucagon-like peptide-1 (GLP-1) receptor
agonist (exenatide) treatment. METHODS: Fifty-four obese patients with T2D were
treated with exenatide for 12weeks. The control group included 54 age-, sex-, and
body mass index (BMI)-matched subjects with normal glucose tolerance. RESULTS:
Patients with T2D had lower irisin than the control group (38.06 [29.29-53.79]
vs. 58.01 [43.07-87.79] ng/mL, P<0.01]. Serum irisin was negatively associated
with BMI (r=-0.178, P<0.05), fasting blood glucose (FBG; r=-0.170, P<0.05), and
glycosylated hemoglobin (HbA1c; r=-0.189, P<0.01) in patients with T2D. Exenatide
treatment markedly increased serum irisin by 19.28ng/mL (12.59-25.98) compared to
baseline (P<0.01). Increased irisin was significantly correlated with decreased
FBG and HbA1c after exenatide treatment (FBG: r=-0.35; HbA1c: r=-0.37; both
P<0.05). CONCLUSIONS: Exenatide treatment significantly increased irisin in
patients with T2D. Post-treatment changes in irisin were correlated with
decreases in FBG and HbA1c. The upregulation of irisin might be a novel mechanism
for the beneficial effects of exenatide in type 2 diabetic patients.
PMID- 27503405
TI - Ten-year hemoglobin A1c trajectories and outcomes in type 2 diabetes mellitus:
The Diabetes & Aging Study.
AB - AIMS: To classify trajectories of long term HbA1c values in patients after
diagnosis of type 2 diabetes and examine each trajectory's associations with
subsequent microvascular and macrovascular events and mortality. METHODS: A
longitudinal follow-up of 28,016 patients newly diagnosed with type 2 diabetes
was conducted. Latent growth mixture modeling was used to identify ten-year HbA1c
trajectories. Cox proportional hazards models were used to assess how HbA1c
trajectories were associated with events (microvascular and macrovascular) and
mortality. RESULTS: We identified 5 HbA1c trajectories: "low stable" (82.5%),
"moderate increasing late" (5.1%), "high decreasing early" (4.9%), "moderate
peaking late" (4.1%) and "moderate peaking early" (3.3%). After adjusting for
average HbA1c, compared to the low stable trajectory, all non-stable trajectories
were associated with higher incidences of microvascular events (hazard ratio (HR)
range, 1.28 (95% CI, 1.08-1.53) (high decreasing early) to 1.45 (95% CI, 1.20
1.75) (moderate peaking early)). The high decreasing early trajectory was
associated with an increased mortality risk (HR, 1.27 (95% CI, 1.03-1.58)).
Trajectories were not associated with macrovascular events. CONCLUSIONS: Non
stable HbA1c trajectories were associated with greater risk of microvascular
events and mortality. These findings suggest a potential benefit of early
diabetes detection, prioritizing good glycemic control, and maintaining control
over time.
PMID- 27503406
TI - Utility of existing diabetes risk prediction tools for young black and white
adults: Evidence from the Bogalusa Heart Study.
AB - AIMS: To evaluate several adult diabetes risk calculation tools for predicting
the development of incident diabetes and pre-diabetes in a bi-racial, young adult
population. METHODS: Surveys beginning in young adulthood (baseline age >=18) and
continuing across multiple decades for 2122 participants of the Bogalusa Heart
Study were used to test the associations of five well-known adult diabetes risk
scores with incident diabetes and pre-diabetes using separate Cox models for each
risk score. Racial differences were tested within each model. Predictive utility
and discrimination were determined for each risk score using the Net
Reclassification Index (NRI) and Harrell's c-statistic. RESULTS: All risk scores
were strongly associated (p<.0001) with incident diabetes and pre-diabetes. The
Wilson model indicated greater risk of diabetes for blacks versus whites with
equivalent risk scores (HR=1.59; 95% CI 1.11-2.28; p=.01). C-statistics for the
diabetes risk models ranged from 0.79 to 0.83. Non-event NRIs indicated high
specificity (non-event NRIs: 76%-88%), but poor sensitivity (event NRIs: -23% to
3%). CONCLUSIONS: Five diabetes risk scores established in middle-aged, racially
homogenous adult populations are generally applicable to younger adults with good
specificity but poor sensitivity. The addition of race to these models did not
result in greater predictive capabilities. A more sensitive risk score to predict
diabetes in younger adults is needed.
PMID- 27503407
TI - A new cyanoacrylate used as bronchial sealant in the endoscopic treatment of
bronchopleural fistual.
PMID- 27503408
TI - An SPR based sensor for allergens detection.
AB - A simple, sensitive and label-free optical sensor method was developed for
allergens analysis using alpha-casein as the biomarker for cow's milk detection,
to be used directly in final rinse samples of cleaning in place systems (CIP) of
food manufacturers. A Surface Plasmon Resonance (SPR) sensor chip consisting of
four sensing arrays enabling the measurement of samples and control binding
events simultaneously on the sensor surface was employed in this work. SPR offers
several advantages in terms of label free detection, real time measurements and
superior sensitivity when compared to ELISA based techniques. The gold sensor
chip was used to immobilise alpha-casein-polyclonal antibody using EDC/NHS
coupling procedure. The performance of the assay and the sensor was first
optimised and characterised in pure buffer conditions giving a detection limit of
58ngmL-1 as a direct binding assay. The assay sensitivity can be further improved
by using sandwich assay format and amplified with nanoparticles. However, at this
stage this is not required as the detection limit achieved exceeded the required
allergens detection levels of 2ugmL-1 for alpha-S1-casein. The sensor
demonstrated good selectivity towards the alpha-casein as the target analyte and
adequate recoveries from CIP final rinse wash samples. The sensor would be useful
tool for monitoring allergen levels after cleaning procedures, providing
additional data that may better inform upon wider food allergen risk management
decision(s) that are made by food manufacturer. In particular, this sensor could
potentially help validate or optimise cleaning practices for a given food
manufacturing process.
PMID- 27503409
TI - Selective isolation of magnetic nanoparticle-mediated heterogeneity subpopulation
of circulating tumor cells using magnetic gradient based microfluidic system.
AB - Relocation mechanisms of the circulating tumor cells (CTCs) from the primary site
to the secondary site through the blood vessel network cause tumor metastasis.
Despite of the importance to diagnose the cancer metastasis by CTCs, still it is
formidable challenge to use in the clinical purpose because of the rarity and the
heterogeneity of CTCs in the cancer patient's peripheral blood sample. In this
study we have developed magnetic force gradient based microfluidic chip (Mag
Gradient Chip) for isolating the total number of CTCs in the sample and
characterizing the state of CTCs simultaneously with respect to the epithelial
cell adhesion molecule (EpCAM) expression level. We have synthesized magnetic
nanoparticles (MNPs) using hydrothermal method and functionalized anti-EpCAM on
their surface for the specific binding with CTCs. The Mag-Gradient Chip designed
to isolate and classify the CTCs by isolating at the different location in the
chip using magnetic force differences depending on the EpCAM expression level. We
observed 95.7% of EpCAM positive and 79.3% of EpCAM negative CTCs isolated in the
Mag-Gradient Chip. At the same time, the 71.3% of isolated EpCAM positive CTCs
were isolated at the first half area whereas the 76.9% of EpCAM negative CTCs
were collected at the latter half area. The Mag-Gradient Chip can isolate the 3ml
of heterogeneous CTCs sample in 1h with high isolating yield. The EpCAM
expression level dose not means essential condition of the metastatic CTCs, but
the Mag-Gradient Chip can shorten the date to diagnose the cancer metastasis in
clinic.
PMID- 27503410
TI - A review of recent progress in lens-free imaging and sensing.
AB - Recently, lens-free imaging has evolved as an alternative imaging technology. The
key advantages of this technology, including simplicity, compactness, low cost,
and flexibility of integration with other components, have facilitated the
realization of many innovative applications, especially, in the fields of the on
chip lens-free imaging and sensing. In this review, we discuss the development of
lens-free imaging, from theory to applications. This article includes the working
principle of lens-free digital inline holography (DIH) with coherent and semi
coherent light, on-chip lens-free fluorescence imaging and sensing, lens-free on
chip tomography, lens-free on-chip gigapixel nanoscopy, detection of
nanoparticles using on-chip microscopy, wide field microscopy, and lens-free
shadow image based point-of-care systems. Additionally, this review also
discusses the lens-free fluorescent imaging and its dependence on structure and
optical design, the advantage of using the compact lens-free driven equilibrium
Fourier transform (DEFT) resolved imaging technique for on-chip tomography, the
pixel super-resolved algorithm for gigapixel imaging, and the lens-free
technology for point-of-care applications. All these low-cost, compact, and fast
processing lens-free imaging and sensing techniques may play a crucial role
especially in the fields of environmental, pharmaceutical, biological, and
clinical applications of the resource-limited settings.
PMID- 27503411
TI - In vitro aging promotes endoplasmic reticulum (ER)-mitochondria Ca2+ cross talk
and loss of store-operated Ca2+ entry (SOCE) in rat hippocampal neurons.
AB - Aging is associated to cognitive decline and susceptibility to neuron death, two
processes related recently to subcellular Ca2+ homeostasis. Memory storage relies
on mushroom spines stability that depends on store-operated Ca2+ entry (SOCE). In
addition, Ca2+ transfer from endoplasmic reticulum (ER) to mitochondria sustains
energy production but mitochondrial Ca2+ overload promotes apoptosis. We have
addressed whether SOCE and ER-mitochondria Ca2+ transfer are influenced by
culture time in long-term cultures of rat hippocampal neurons, a model of
neuronal aging. We found that short-term cultured neurons show large SOCE, low
Ca2+ store content and no functional coupling between ER and mitochondria. In
contrast, in long-term cultures reflecting aging neurons, SOCE is essentially
lost, Stim1 and Orai1 are downregulated, Ca2+ stores become overloaded, Ca2+
release is enhanced, expression of the mitochondrial Ca2+ uniporter (MCU)
increases and most Ca2+ released from the ER is transferred to mitochondria.
These results suggest that neuronal aging is associated to increased ER
mitochondrial cross talking and loss of SOCE. This subcellular Ca2+ remodeling
might contribute to cognitive decline and susceptibility to neuron cell death in
the elderly.
PMID- 27503413
TI - KLICK syndrome: recognizable phenotype and hot-spot POMP mutation.
PMID- 27503412
TI - Amorphous nickel boride membrane on a platinum-nickel alloy surface for enhanced
oxygen reduction reaction.
AB - The low activity of the oxygen reduction reaction in polymer electrolyte membrane
fuel cells is a major barrier for electrocatalysis, and hence needs to be
optimized. Tuning the surface electronic structure of platinum-based bimetallic
alloys, a promising oxygen reduction reaction catalyst, plays a key role in
controlling its interaction with reactants, and thus affects the efficiency. Here
we report that a dealloying process can be utilized to experimentally fabricate
the interface between dealloyed platinum-nickel alloy and amorphous nickel boride
membrane. The coating membrane works as an electron acceptor to tune the surface
electronic structure of the platinum-nickel catalyst, and this composite catalyst
composed of crystalline platinum-nickel covered by amorphous nickel boride
achieves a 27-times enhancement in mass activity relative to commercial
platinum/carbon at 0.9 V for the oxygen reduction reaction performance. Moreover,
this interactional effect between a crystalline surface and amorphous membrane
can be readily generalized to facilitate the 3-times higher catalytic activity of
commercial platinum/carbon.
PMID- 27503414
TI - Interactions of two odorant-binding proteins influence insect chemoreception.
AB - It is well known that the odorant-binding proteins (OBPs) play crucial roles in
insect olfactory detection. To explore if interactions of OBPs affect olfactory
coding in the rice leaffolder Cnaphalocrocis medinalis ligand-binding
experiments, molecular docking, RNA interference and electrophysiological
recording were performed. The binding activity of two C. medinalis OBPs
(CmedOBPs) to rice plant volatiles showed wide flexibility depending on the
structure of ligands and interactions of CmedOBPs involved. The binding sites of
CmedOBP2 and CmedOBP3 to rice plant volatiles were well predicted by three
dimensional structure modelling and molecular docking experiments. In addition,
the interactions of these two CmedOBPs in the perception of rice volatiles were
demonstrated by RNA interference experiments. When a single double-stranded RNA
(dsRNA)-CmedOBP2 was injected, the expression of CmedOBP2 was significantly
reduced and the expression of CmedOBP3 was significantly increased, and vice
versa. When both dsRNA-CmedOBP2 and 3 were injected together, greater reduction
of electroantennogram responses to rice plant volatiles was induced than that
seen with individual injection of either dsRNA-CmedOBP2 or dsRNA-CmedOBP3. These
results clearly indicate that the interactions of CmedOBP2 and CmedOBP3 have
significant effects on C. medinalis during the detection of host plant volatiles.
PMID- 27503415
TI - Quantitative trait gene Slit2 positively regulates murine hematopoietic stem cell
numbers.
AB - Hematopoietic stem cells (HSC) demonstrate natural variation in number and
function. The genetic factors responsible for the variations (or quantitative
traits) are largely unknown. We previously identified a gene whose differential
expression underlies the natural variation of HSC numbers in C57BL/6 (B6) and
DBA/2 (D2) mice. We now report the finding of another gene, Slit2, on chromosome
5 that also accounts for variation in HSC number. In reciprocal chromosome 5
congenic mice, introgressed D2 alleles increased HSC numbers, whereas B6 alleles
had the opposite effect. Using gene array and quantitative polymerase chain
reaction, we identified Slit2 as a quantitative trait gene whose expression was
positively correlated with the number of HSCs. Ectopic expression of Slit2 not
only increased the number of the long-term colony forming HSCs, but also enhanced
their repopulation capacity upon transplantation. Therefore, Slit2 is a novel
quantitative trait gene and a positive regulator of the number and function of
murine HSCs. This finding suggests that Slit2 may be a potential therapeutic
target for the effective in vitro and in vivo expansion of HSCs without
compromising normal hematopoiesis.
PMID- 27503417
TI - Revealing the role of catechol moieties in the interactions between peptides and
inorganic surfaces.
AB - Catechol (1,2-dihydroxy benzene) moieties are being widely used today in new
adhesive technologies. Understanding their mechanism of action is therefore of
high importance for developing their applications in materials science. This
paper describes a single-molecule study of the interactions between catechol
related amino acid residues and a well-defined titanium dioxide (TiO2) surface.
It is the first quantified measurement of the adhesion of these residues with a
well-defined TiO2 surface. Single-molecule force spectroscopy measurements with
AFM determined the role of different substitutions of the catechol moiety on the
aromatic ring in the adhesion to the surface. These results shed light on the
nature of interactions between these residues and inorganic metal oxide surfaces.
This information is important for the design and fabrication of catechol-based
materials such as hydrogels, coatings, and composites. Specifically, the
interaction with TiO2 is important for the development of solar cells.
PMID- 27503416
TI - Effects of race and sex on cerebral hemodynamics, oxygen delivery and blood flow
distribution in response to high altitude.
AB - To assess racial, sexual, and regional differences in cerebral hemodynamic
response to high altitude (HA, 3658 m). We performed cross-sectional comparisons
on total cerebral blood flow (TCBF = sum of bilateral internal carotid and
vertebral arterial blood flows = QICA + QVA), total cerebrovascular resistance
(TCVR), total cerebral oxygen delivery (TCOD) and QVA/TCBF (%), among six groups
of young healthy subjects: Tibetans (2-year staying) and Han (Han Chinese) at sea
level, Han (2-day, 1-year and 5-year) and Tibetans at HA. Bilateral ICA and VA
diameters and flow velocities were derived from duplex ultrasonography; and
simultaneous measurements of arterial pressure, oxygen saturation, and hemoglobin
concentration were conducted. Neither acute (2-day) nor chronic (>1 year)
responses showed sex differences in Han, except that women showed lower TCOD
compared with men. Tibetans and Han exhibited different chronic responses
(percentage alteration relative to the sea-level counterpart value) in TCBF (-17%
vs. 0%), TCVR (22% vs. 12%), TCOD (0% vs. 10%) and QVA/TCBF (0% vs. 2.4%,
absolute increase), with lower resting TCOD found in SL- and HA-Tibetans. Our
findings indicate racial but not sex differences in cerebral hemodynamic
adaptations to HA, with Tibetans (but not Han) demonstrating an altitude-related
change of CBF distribution.
PMID- 27503418
TI - Evaluation of Life Events in Major Depression: Assessing Negative Emotional Bias.
AB - BACKGROUND: Overly negative appraisals of negative life events characterize
depression but patterns of emotion bias associated with life events in depression
are not well understood. The goal of this paper is to determine under which
situations emotional responses are stronger than expected given life events and
which emotions are biased. METHODS: Depressed (n = 16) and non-depressed (n = 14)
participants (mean age = 41.4 years) wrote about negative life events involving
their own actions and inactions, and rated the current emotion elicited by those
events. They also rated emotions elicited by someone else's actions and
inactions. These ratings were compared with evaluations provided by a second,
'benchmark' group of non-depressed individuals (n = 20) in order to assess the
magnitude and direction of possible biased emotional reactions in the two groups.
RESULTS: Participants with depression reported greater anger and disgust than
expected in response to both actions and inactions, whereas they reported greater
guilt, shame, sadness, responsibility and fear than expected in response to
inactions. Relative to non-depressed and benchmark participants, depressed
participants were overly negative in the evaluation of their own life events, but
not the life events of others. CONCLUSION: A standardized method for establishing
emotional bias reveals a pattern of overly negative emotion only in depressed
individuals' self-evaluations, and in particular with respect to anger and
disgust, lending support to claims that major depressives' evaluations represent
negative emotional bias and to clinical interventions that address this bias.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27503419
TI - Reducing low-value interventions in the emergency department: you may be part of
the problem.
PMID- 27503420
TI - Corrigendum: A Toxic RNA Catalyzes the In Cellulo Synthesis of Its Own Inhibitor.
PMID- 27503422
TI - Distal Normograde Intramedullary Pin and Locking Plate Placement in the Canine
Humerus: A Cadaveric Study.
AB - OBJECTIVE: To identify a repeatable anatomic landmark for pin insertion and to
describe the technique for placement of a distal normograde intramedullary (IM)
pin of approximately 35% of the IM diameter using this approach combined with a
locking compression plate (LCP) on the medial aspect of the canine humerus. STUDY
DESIGN: Ex vivo anatomic study. SAMPLE POPULATION: Canine cadavers (n=10
Greyhounds). METHODS: An anatomic landmark for pin insertion was identified based
on three-dimensional reconstructions of previous elbow computed tomography
studies and cadaveric dissection of the medial aspect of the humeral condyle.
Bilateral distal normograde IM pin and LCP placement were performed and confirmed
radiographically and by disarticulation and sagittal sectioning. RESULTS: The
anatomic landmark for pin insertion was consistently identified in each specimen
using the technique described. Distal normograde insertion of a 3.5 mm IM pin was
possible in Greyhound cadaveric humeri at the described location in conjunction
with a 3.5 mm LCP with fixed angle, locked screws. A monocortical locking screw
was required to avoid interference with the IM pin in 28 of 60 of the 3 proximal
screw holes. No pin interference was encountered in any of the distal screw
holes. CONCLUSION: The anatomic landmark and technique described in our study
enabled repeatable successful placement of a distal normograde IM pin of
approximately 35% of the IM diameter combined with an LCP on the medial aspect of
the canine humerus. This technique may be useful for locking plate-rod fixation
of distal humeral diaphyseal fractures.
PMID- 27503423
TI - Characterization of fibrosis changes in chronic hepatitis C patients after
virological cure: A systematic review with meta-analysis.
AB - BACKGROUND AND AIM: Virological cure becomes available for most patients with
chronic hepatitis C (CHC), but residual fibrosis can be an independent risk
factor for liver-related complications. We aimed to characterize fibrosis change
in CHC patients achieved virological cure. METHODS: We did a systematic
literature search for studies that had pre and post-treatment evaluations of
histologic fibrosis in CHC patients with sustained virological response (SVR). We
identified the association of SVR with the incidence, extent, and velocity of
fibrosis change. RESULTS: Overall, 3243 patients were included. Interferon-based
regimens were used for all the patients, achieving a median SVR prevalence of
36.2%. Biopsy interval ranged from 1 to 10 years. Mean baseline fibrosis score
(METAVIR) was 2.3 points. Compared with non-SVR patients, SVR patients could have
higher incidence of fibrosis regression (35.1% vs 17.0%; OR: 3.3; P < 0.001),
regardless of baseline fibrosis severity, way of biopsy evaluation, treatment
regimen, or study design, and could have more extent of reduction (-0.31 points
vs -0.00 points; P = 0.004). Baseline advanced fibrosis (F > 2) was associated
with more rapid regression in both SVR and non-SVR patients (P < 0.05 for both).
SVR patients could have lower incidence of fibrosis progression and maintenance
than non-SVR patients by 4.8% versus 23.1% (OR: 0.20; P = 0.008) and 42.9% versus
55.2% (OR: 0.53; P < 0.001), respectively. CONCLUSIONS: There could be a
favorable characteristic of fibrosis regression in SVR patients. However,
residential fibrosis may remain an issue because of a non-ignorable prevalence of
fibrosis maintenance among these patients.
PMID- 27503424
TI - A Nanoscale Interface Promoting Molecular and Functional Differentiation of
Neural Cells.
AB - Potassium channels and aquaporins expressed by astrocytes are key players in the
maintenance of cerebral homeostasis and in brain pathophysiologies. One major
challenge in the study of astrocyte membrane channels in vitro, is that their
expression pattern does not resemble the one observed in vivo. Nanostructured
interfaces represent a significant resource to control the cellular behaviour and
functionalities at micro and nanoscale as well as to generate novel and more
reliable models to study astrocytes in vitro. However, the potential of
nanotechnologies in the manipulation of astrocytes ion channels and aquaporins
has never been previously reported. Hydrotalcite-like compounds (HTlc) are
layered materials with increasing potential as biocompatible nanoscale interface.
Here, we evaluate the effect of the interaction of HTlc nanoparticles films with
primary rat neocortical astrocytes. We show that HTlc films are biocompatible and
do not promote gliotic reaction, while favouring astrocytes differentiation by
induction of F-actin fibre alignment and vinculin polarization. Western Blot,
Immunofluorescence and patch-clamp revealed that differentiation was accompanied
by molecular and functional up-regulation of both inward rectifying potassium
channel Kir 4.1 and aquaporin 4, AQP4. The reported results pave the way to
engineering novel in vitro models to study astrocytes in a in vivo like
condition.
PMID- 27503425
TI - The value of 11C-methionine PET in the early differentiation between tumour
recurrence and radionecrosis in patients treated for a high-grade glioma and
indeterminate MRI.
AB - OBJECTIVE: To evaluate the contribution of 11C-Methionine PET in the early
differentiation between tumour recurrence and radionecrosis in patients treated
for a high grade glioma. METHOD: The study included 30 patients with glioma
(III/IV grade) treated with surgery/radiotherapy/chemotherapy (5-8 months) and
with an indeterminate MRI. All patients underwent a 11C-Methione PET (within 15
days of MRI) and studies were visually analysed (intensity and morphology of
uptake), quantified (SUV max/SUV mean background), and coregistered to MRI (3D
Flair). Patient management was decided by the neuro-oncology committee to
clinical and imaging follow-up, second-line treatment, or surgery. RESULTS: There
were 23 11C-Methionine PET studies visually positive. Morphology of uptake was
focal in 15, diffuse in 4, and ring-shaped in 4. Three out of the focal uptake
cases underwent resection (Histopathology +). Sixteen underwent second-line
therapy (11 responded; 5 progressed). The 4 cases with ring-shaped uptake were
followed-up, and progression was found in 2 (true-positive), and disease-free in
2 (follow-up of 6 and 7 months, respectively) (false-positive). Seven out of 11C
Methionine studies PET were visually negative, and all of them were disease-free
(follow-up of 3-12 months). SUV lesion/background was 2.79+/-1.35 in tumour
recurrence, and 1.53+/-0.39 in radionecrosis (P<.05). Taking into account a SUV
lesion/background threshold of 2.35, the sensitivity and specificity values were
90.5% and 100%, respectively. CONCLUSION: Visual analysis, quantitative and
PET/MRI coregistration of 11C-Methionine PET showed their complementary role in
patients with indeterminate MRI results, thus allowing early differentiation
between tumour recurrence and radionecrosis, and helping in the individual
therapy approach.
PMID- 27503426
TI - The mRNA capping enzyme of Saccharomyces cerevisiae has dual specificity to
interact with CTD of RNA Polymerase II.
AB - RNA Polymerase II (RNAPII) uniquely possesses an extended carboxy terminal domain
(CTD) on its largest subunit, Rpb1, comprising a repetitive Tyr1Ser2Pro3Thr4
Ser5Pro6Ser7 motif with potential phosphorylation sites. The phosphorylation of
the CTD serves as a signal for the binding of various transcription regulators
for mRNA biogenesis including the mRNA capping complex. In eukaryotes, the 5
prime capping of the nascent transcript is the first detectable mRNA processing
event, and is crucial for the productive transcript elongation. The binding of
capping enzyme, RNA guanylyltransferases to the transcribing RNAPII is known to
be primarily facilitated by the CTD, phosphorylated at Ser5 (Ser5P). Here we
report that the Saccharomyces cerevesiae RNA guanylyltransferase (Ceg1) has dual
specificity and interacts not only with Ser5P but also with Ser7P of the CTD. The
Ser7 of CTD is essential for the unconditional growth and efficient priming of
the mRNA capping complex. The Arg159 and Arg185 of Ceg1 are the key residues that
interact with the Ser5P, while the Lys175 with Ser7P of CTD. These interactions
appear to be in a specific pattern of Ser5PSer7PSer5P in a tri-heptad CTD
(YSPTSPPS YSPTSPSP YSPTSPPS) and provide molecular insights into the Ceg1-CTD
interaction for mRNA transcription.
PMID- 27503427
TI - Energy Bandgap and Edge States in an Epitaxially Grown Graphene/h-BN
Heterostructure.
AB - Securing a semiconducting bandgap is essential for applying graphene layers in
switching devices. Theoretical studies have suggested a created bulk bandgap in a
graphene layer by introducing an asymmetry between the A and B sub-lattice sites.
A recent transport measurement demonstrated the presence of a bandgap in a
graphene layer where the asymmetry was introduced by placing a graphene layer on
a hexagonal boron nitride (h-BN) substrate. Similar bandgap has been observed in
graphene layers on metal substrates by local probe measurements; however, this
phenomenon has not been observed in graphene layers on a near-insulating
substrate. Here, we present bulk bandgap-like features in a graphene layer
epitaxially grown on an h-BN substrate using scanning tunneling spectroscopy. We
observed edge states at zigzag edges, edge resonances at armchair edges, and
bandgap-like features in the bulk.
PMID- 27503428
TI - Paenibacillus hispanicus sp. nov. isolated from Triticum aestivum roots.
AB - A bacterial strain designated AMTAE16T was isolated from a root of wheat in
Spain. Phylogenetic analyses based on 16S rRNA gene sequences placed the isolate
in the genus Paenibacilluswith its closest relative being Paenibacillus
daejeonensis AP-20T with 99.0 % 16S rRNA gene sequence similarity. DNA-DNA
hybridization studies showed a mean of 30 % DNADNA relatedness between strain
AMTAE16T and the type strain of P. daejeonensis. The isolate was a Gram
stainvariable, motile and sporulating rod. Catalase and oxidase activities were
positive. Gelatin and starch were hydrolysed but not casein. Growth was supported
by many carbohydrates and organic acids as carbon source. MK-7 was the only
menaquinone detected and anteiso-C15 : 0, C16 : 0 and iso-C16 : 0 were the major
fatty acids. The major polar lipids were diphosphatidylglycerol,
phosphatidylglycerol, phosphatidylethanolamine, two unidentified
aminophospholipids, four unidentified phospholipids and two unidentified lipids.
meso-Diaminopimelic acid was detected in the peptidoglycan. The DNA G+C content
was 55.4 mol%. Phylogenetic, chemotaxonomic and phenotypic analyses showed that
strain AMTAE16T represents a novel species of the genus Paenibacillus, for which
the name Paenibacillus hispanicus sp. nov. is proposed. The type strain is
AMTAE16T(=LMG 29501T=CECT 9124T).
PMID- 27503429
TI - Post chemotherapy retroperitoneal lymph node dissection in germ cell tumor:
robotic way.
AB - Post chemotherapy residual masses are considered extremely challenging to remove
even by the most experienced laparoscopic surgeons. Robotic technology has added
a new dimension to the management of such cases and has lessened the fear and
discomfort associated with such challenging surgery but is still evolving. We
present our experience of management of post chemotherapy residual mass with
robotic assistance along with tips and tricks required to perform such procedure.
PMID- 27503431
TI - Enhancing photoluminescence properties of SiC/SiO2 coaxial nanocables by making
oxygen vacancies.
AB - Coaxial nanocables (CNs) with an SiC core and a SiO2 shell were fabricated at a
large scale by a simple and low cost method. The thickness of the SiO2 shell
could be controlled by etching in 1 M NaOH aqueous solution for different amounts
of time. XRD, SEM, TEM, HRTEM, PL and UV-Vis spectra were adopted to investigate
the morphology and optical properties of the obtained SiC/SiO2CNs. Blue
photoluminescence was observed at room temperature from the coaxial structure.
The intensity of the single emission band at 468 nm (2.65 eV) exhibited a strong
dependence on the thickness of the SiO2 layer and was significantly enhanced when
the outer SiO2 shell had a thickness of 2.8 nm. The enhancement effect was
attributed to oxygen vacancies (OV) and this was verified by deliberately
enriching the surface OV through hydrogen treatment.
PMID- 27503430
TI - Tuberculosis infection control practices and associated factors among health care
workers in health centers of West Gojjam zone, Northwest Ethiopia: a cross
sectional study.
AB - BACKGROUND: Tuberculosis (TB) remains a major global health problem. The emerging
epidemic of multi- and extensively drug-resistant (M/XDR) TB further imperils
health workers, patients and public health. Health facilities with inadequate
infection control are risky environments for the emergence and transmission of
TB. There was no study that presented data on infection control practices of
health care workers. This study aimed to assess tuberculosis infection control
practices and associated factors among health care workers in West Gojjam Zone,
Northwest Ethiopia. METHODS: Institution based quantitative cross-sectional study
triangulated with qualitative observation and key informant interview was
conducted. Six hundred sixty two health care workers were selected by multistage
random sampling method. Self-administered structured questionnaire was used to
collect quantitative data. Observation checklists and key informant interview
guides were used to collect qualitative data. Quantitative data were entered in
to Epi Info version 3.5.3 and analyzed using SPSS version 20. Odds ratio with 95
% confidence interval was used to identify factors associated with TB infection
control practice of health care workers. Qualitative data were translated,
transcribed, analyzed and triangulated with the quantitative findings. RESULTS:
The proportion of proper TB infection control (TBIC) practices was 38 %.
Qualitative data showed that administrative, environmental and personal
respiratory protection control measures were not practiced well. Knowledge on the
presence of TBIC plan [AOR = 4.25, 95 % CI: 2.46 - 7.35], knowledge on the
presence of national guideline [AOR = 8.95, 95 % CI: 4.35 - 18.40] and working
department of the health care workers were independent predictors of TBIC
practices. CONCLUSIONS: The proportion of proper TBIC practices of health care
workers was low. TBIC practices were determined by knowing the presence of TBIC
plan and national guideline and working department. Hence, supportive supervision
and trainings should be given to health care workers who are working other than
TB clinics to improve the knowledge of TBIC plan and guidelines. Health centers
shall prepare TBIC plans and orient all health care workers.
PMID- 27503432
TI - Could participant-produced photography augment therapeutic interventions for
people with intellectual disabilities? A systematic review of the available
evidence.
AB - BACKGROUND: People with intellectual disabilities are entitled to equitable
access to psychological support. Traditional therapeutic approaches often rely on
a person's ability to verbally articulate a description of their life, which can
be particularly difficult for emotionally salient information. METHODS: A
systematic literature review was undertaken to determine the evidence base
underpinning the use of participant-produced photography within therapeutic
settings. Evidence across a range of specialisms was examined in order to
extrapolate areas of best practice and make recommendations for its
implementation alongside people with intellectual disabilities. RESULTS: A
systematic search of peer-reviewed journals identified 13 relevant documents.
Participant-produced photography showed promise, although evidence pertaining
specifically to people with intellectual disabilities was sparse ( n = 2).
CONCLUSION: Participant-produced photography within therapeutic settings shows
promise for people with intellectual disabilities. Methodological limitations
made it difficult to derive firm conclusions regarding the effectiveness of
different approaches. Implications for clinical and research practice are
discussed.
PMID- 27503433
TI - Capsule Commentary on Axon et al., Differential Impact of Homelessness on
Glycemic Control in Veterans with Type 2 Diabetes Mellitus.
PMID- 27503434
TI - Capsule Commentary on Bailey et al., Effect of Gaining Insurance Coverage on
Smoking Cessation in Community Health Centers: A Cohort Study.
PMID- 27503435
TI - Erratum to: Improvement Happens -- Learning to Better Care for "Super-Utilizers"
at Denver Health: An Interview with Holly Batal.
PMID- 27503437
TI - Capsule Commentary of Shah et al., Targeted Reminder Phone Calls to Patients at
High Risk to No-Show for Primary Care Appointment: A Randomized Trial.
PMID- 27503436
TI - Targeted Reminder Phone Calls to Patients at High Risk of No-Show for Primary
Care Appointment: A Randomized Trial.
AB - BACKGROUND: No-shows, or missed appointments, are a problem for many medical
practices. They result in fragmented care and reduce access for all patients.
OBJECTIVE: To determine whether telephone reminder calls targeted to patients at
high risk of no-show can reduce no-show rates. DESIGN: Single-center randomized
controlled trial. PARTICIPANTS: A total of 2247 primary care patients in a
hospital-based primary care clinic at high risk of no-show (>15 % risk) for their
appointment in 7 days. INTERVENTION: Seven days prior to their appointment,
intervention arm patients were placed in a calling queue to receive a reminder
phone call from a patient service coordinator. Coordinators were trained to
engage patients in concrete planning. All patients received an automated phone
call (usual care). MAIN MEASURES: Primary outcome was no-show rate. Secondary
outcomes included arrival rate, cancellation rate, reschedule rate, time to
cancellation, and change in revenue. KEY RESULTS: The no-show rate in the
intervention arm (22.8 %) was significantly lower (absolute risk difference -6.4
%, p < 0.01, 95 % CI [-9.8 to -3.0 %]) than that in the control arm (29.2 %).
Arrival, cancellation, and reschedule rates did not differ significantly. In the
intervention arm, rescheduling and cancellations occurred further in advance of
the appointment (mean difference, 0.35 days; 95 % CI [0.07-0.64]; p = 0.01).
Reimbursement did not differ significantly. CONCLUSIONS: A phone call 7 days
prior to an appointment led to a significant reduction in no-shows and increased
reimbursement among patients at high risk of no-show. The use of targeted
interventions may be of interest to practices taking on increased accountability
for population health.
PMID- 27503438
TI - Vital Signs Are Still Vital: Instability on Discharge and the Risk of Post
Discharge Adverse Outcomes.
AB - BACKGROUND: Vital sign instability on discharge could be a clinically objective
means of assessing readiness and safety for discharge; however, the association
between vital sign instability on discharge and post-hospital outcomes is
unclear. OBJECTIVE: To assess the association between vital sign instability at
hospital discharge and post-discharge adverse outcomes. DESIGN: Multi-center
observational cohort study using electronic health record data. Abnormalities in
temperature, heart rate, blood pressure, respiratory rate, and oxygen saturation
were assessed within 24 hours of discharge. We used logistic regression adjusted
for predictors of 30-day death and readmission. PARTICIPANTS: Adults (>=18 years)
with a hospitalization to any medicine service in 2009-2010 at six hospitals
(safety-net, community, teaching, and non-teaching) in north Texas. MAIN
MEASURES: Death or non-elective readmission within 30 days after discharge. KEY
RESULTS: Of 32,835 individuals, 18.7 % were discharged with one or more vital
sign instabilities. Overall, 12.8 % of individuals with no instabilities on
discharge died or were readmitted, compared to 16.9 % with one instability, 21.2
% with two instabilities, and 26.0 % with three or more instabilities (p <
0.001). The presence of any (>=1) instability was associated with higher risk
adjusted odds of either death or readmission (AOR 1.36, 95 % CI 1.26-1.48), and
was more strongly associated with death (AOR 2.31, 95 % CI 1.91-2.79).
Individuals with three or more instabilities had nearly fourfold increased odds
of death (AOR 3.91, 95 % CI 1.69-9.06) and increased odds of 30-day readmission
(AOR 1.36, 95 % 0.81-2.30) compared to individuals with no instabilities. Having
two or more vital sign instabilities at discharge had a positive predictive value
of 22 % and positive likelihood ratio of 1.8 for 30-day death or readmission.
CONCLUSIONS: Vital sign instability on discharge is associated with increased
risk-adjusted rates of 30-day mortality and readmission. These simple vital sign
criteria could be used to assess safety for discharge, and to reduce 30-day
mortality and readmissions.
PMID- 27503439
TI - Patient Relationship Management: What the U.S. Healthcare System Can Learn from
Other Industries.
AB - As the U.S. healthcare system moves to value-based care, the importance of
engaging patients and families continues to intensify. However, simply engaging
patients and families to improve their subjective satisfaction will not be enough
for providers who want to maximize value. True optimization entails developing
deep and long-term relationships with patients. We suggest that healthcare
organizations must build such a discipline of "patient relationship management"
(PRM) just as companies in non-healthcare industries have done with the concept
of customer relationship management (CRM). Some providers have already made
strides in this area, but overall it has been underemphasized or ignored by most
healthcare systems to date. As healthcare providers work to develop their
dedicated PRM systems, tools, and processes, we suggest they may benefit from
emulating companies in other industries who have been able to engage their
customers in innovative ways while acknowledging the differences between
healthcare and other industries.
PMID- 27503440
TI - Patient-Centered Medical Home Implementation in the Veterans Health
Administration and Primary Care Use: Differences by Patient Comorbidity Burden.
AB - BACKGROUND: The patient-centered medical home (PCMH) model has several components
to improve care for patients with high comorbidity, including greater access to
face-to-face primary care. OBJECTIVE: We examined whether high-comorbidity
patients had larger increases in primary care provider (PCP) visits attributable
to PCMH implementation in a large integrated health system relative to other
patients enrolled in primary care. DESIGN, SUBJECTS AND MAIN MEASURES: This
longitudinal study examined a 1 % random sample of 9.3 million patients enrolled
in the Veterans Health Administration (VHA) at any time between 2003 and 2013.
Face-to-face visits with PCPs per quarter were identified through VHA
administrative data. Comorbidity was measured using the Gagne index and patients
with a weighted score of >= 2 were defined as high comorbidity. We applied
interrupted time-series models to estimate marginal changes in PCP visits
attributable to PCMH implementation. Differences in marginal changes were
calculated across comorbidity groups (high vs. low). Analyses were stratified by
age group to account for Medicare eligibility. KEY RESULTS: Among age 65+
patients, PCMH was associated with greater PCP visits starting four and ten
quarters following implementation for high- and low-comorbidity patients,
respectively. Changes were larger for high-comorbidity patients (eight to 11
greater visits per 1000 patients per quarter). Among patients age < 65, PCMH was
associated with greater visits for high-comorbidity patients starting eight
quarters following implementation, but fewer visits for low-comorbidity patients
in all quarters. The difference in visit changes across groups ranged from 18 to
67 visits per 1000 patients per quarter. CONCLUSIONS: Increases in PCP visits
attributable to PCMH were greater among patients with higher comorbidity. Health
systems implementing PCMH should account for population-level comorbidity burden
when planning for PCMH-related changes in PCP utilization.
PMID- 27503441
TI - Comparison of immediate breast reconstruction after mastectomy and mastectomy
alone for breast cancer: A meta-analysis.
AB - BACKGROUND: The purpose of this study was to compare patient outcomes between
immediate breast reconstruction (IBR) after mastectomy and mastectomy alone.
METHODS: We conducted a comprehensive literature search of PUBMED, EMBASE, Web of
Science, and Cochrane Library. The primary outcomes evaluated in this review were
overall survival, disease-free survival and local recurrence. Secondary outcome
was the incidence of surgical site infection. All data were analyzed using Review
Manager 5.3. RESULTS: Thirty-one studies, involving of 139,894 participants were
included in this paper. Pooled data demonstrated that women who had IBR after
mastectomy were more likely to experience surgical site infection than those
treated with mastectomy alone (risk ratios 1.51, 95% CI: 1.22-1.87; p = 0.0001).
There were no significant differences in overall survival (hazard ratios 0.92,
95% CI: 0.80-1.06; p = 0.25) and disease-free survival (hazard ratios 0.96, 95%
CI: 0.84-1.10; p = 0.54) between IBR after mastectomy and mastectomy alone. No
significant difference was found in local recurrence between two groups (risk
ratios 0.92, 95% CI: 0.75-1.13; p = 0.41). CONCLUSIONS: Our study demonstrates
that IBR after mastectomy does not affect the overall survival and disease-free
survival of breast cancer. Besides, no evidence shows that IBR after mastectomy
increases the frequency of local recurrence.
PMID- 27503442
TI - Re: Infection prevention in implant surgery - A review of the surgical evidence,
guidelines and a checklist.
PMID- 27503443
TI - Corrigendum to "Alkaline bioleaching of municipal solid waste incineration fly
ash by autochthonous extremophiles" [Chemosphere vol. 160 (2016) 54-61].
PMID- 27503444
TI - Patterns of disease relapse in primary extremity soft-tissue sarcoma.
AB - BACKGROUND: Extremity soft-tissue sarcomas comprise a range of distinct
histological subtypes. This study aimed to characterize the patterns of disease
relapse in patients undergoing resection of primary extremity soft-tissue
sarcoma. METHODS: All patients who had resection of primary extremity soft-tissue
sarcoma at the Royal Marsden Hospital between January 2004 and January 2014 were
identified from an institutional database. RESULTS: In the period examined, 556
patients underwent resection. The most common histological subtypes were
undifferentiated pleomorphic sarcoma (169 patients, 30.4 per cent), well
differentiated liposarcoma (63, 11.3 per cent), myxoid liposarcoma (62, 11.2 per
cent), myxofibrosarcoma (54, 9.7 per cent) and leiomyosarcoma (39, 7.0 per cent).
Local recurrence-free survival (LRFS) did not differ significantly between
histological subtypes (P = 0.222). Distant metastasis-free survival (DMFS) and
disease-specific survival (DSS) were found to differ significantly between
subtypes (P < 0.001 for both DMFS and DSS), with the worst outcomes in patients
with undifferentiated pleomorphic sarcoma (5-year survival rate: 56.8 (95 per
cent c.i. 52.5 to 61.1) per cent for DMFS; 60.1 (55.6 to 64.6) per cent for DSS).
However, on multivariable analysis, histological subtype was not found to be
independently prognostic for LRFS, DMFS or DSS. Metastatic disease developed in
149 patients, with the lungs being the most common site of first metastasis (120
patients, 80.5 per cent). The site of first metastasis differed between subtypes,
with extrapulmonary metastases predominant in myxoid liposarcoma (11 of 13
patients; P < 0.001). CONCLUSION: Although histological subtype was not found to
be an independent prognostic factor for oncological outcomes, the site of first
metastasis differed significantly between subtypes.
PMID- 27503445
TI - Seroprevalence of hepatitis B virus surface antigen (HBsAg) among clients
visiting 'Tefera Hailu' memorial hospital, Sekota, Northern Ethiopia.
AB - BACKGROUND: Hepatitis B virus is one of the most causative agents of human liver
disease, including acute and chronic hepatitis, cirrhosis and hepatocellular
carcinoma. The disease is a great health problem worldwide, with estimated of 350
million chronically infected people. OBJECTIVE: The aim of this study was to
determine the prevalence of hepatitis B virus in Tefera Hailu Memorial Hospital
(THMH) for the last three years (2013, 2014, 2015) by using secondary data.
METHOD: A three year retrospective record review was conducted from March 01/2015
July 30/2015. All registered data for hepatitis B virus serological screening of
the specified period were included. The data were collected by predesigned data
collection sheet. The sample size was calculated by simple statistical estimation
to be 149 for each year. RESULT: Of 482 subjects, 215 (44.60 %) were females and
267 (55.40 %) were males. The overall prevalence of HBV was 102 (21.16 %). The
positivity rate was 69 (14.31 %) in the age group between 15 and 45. There was a
decrease in the prevalence of HBV from 2012 up to 2014. CONCLUSION: The
seroprevalence of HBsAg was higher in males than in females and the yearly
prevalence decreases from 2012-2014. But HBV infection is still a public health
problem in Ethiopia. Therefore intensification of health education concerning
modes of transmission and prevention of HBV, early case finding and treatment is
recommended to reduce the spread of the disease.
PMID- 27503446
TI - Imaging the Addicted Brain: Alcohol.
AB - Alcohol use disorder (AUD) represents a major public health issue due to its
prevalence and severe health consequences. It may affect several aspects of an
individual's life including work and relationships, and it also increases risk
for additional problems such as brain injury. The causes and outcomes of AUD are
varied; thus, attempting to understand this complex phenomenon requires
investigation from multiple perspectives. Magnetic resonance imaging (MRI) is a
powerful means to investigate brain anatomical and functional alterations related
to AUD. Recent advances in MRI methods allow better investigation of the
alterations to structural and functional brain networks in AUD. Here, we focus on
findings from studies using multiple MRI techniques, which converge to support
the considerable vulnerability of frontal systems. Indeed, MRI studies provide
evidence for a "disconnection syndrome" which could be involved in the poor
behavioral control observed in AUD.
PMID- 27503448
TI - Neurobiological Basis of Hypersexuality.
AB - Until now, hypersexuality has not found entry into the common diagnostic
classification systems. However it is a frequently discussed phenomenon
consisting of excessive sexual appetite that is maladaptive for the individual.
Initial studies investigated the neurobiological underpinnings of hypersexuality,
but current literature is still insufficient to draw unequivocal conclusions. In
the present review, we summarize and discuss findings from various perspectives:
neuroimaging and lesion studies, studies on other neurological disorders that are
sometimes accompanied by hypersexuality, neuropharmacological evidence, genetic
as well as animal studies. Taken together, the evidence seems to imply that
alterations in the frontal lobe, amygdala, hippocampus, hypothalamus, septum, and
brain regions that process reward play a prominent role in the emergence of
hypersexuality. Genetic studies and neuropharmacological treatment approaches
point at an involvement of the dopaminergic system.
PMID- 27503447
TI - Effects of Marijuana Use on Brain Structure and Function: Neuroimaging Findings
from a Neurodevelopmental Perspective.
AB - Marijuana, behind only tobacco and alcohol, is the most popular recreational drug
in America with prevalence rates of use rising over the past decade. A wide range
of research has highlighted neurocognitive deficits associated with marijuana
use, particularly when initiated during childhood or adolescence. Neuroimaging,
describing alterations to brain structure and function, has begun to provide a
picture of possible mechanisms associated with the deleterious effects of
marijuana use. This chapter provides a neurodevelopmental framework from which
recent data on brain structural and functional abnormalities associated with
marijuana use is reviewed. Based on the current data, we provide aims for future
studies to more clearly delineate the effects of marijuana on the developing
brain and to define underlying mechanisms of the potential long-term negative
consequences of marijuana use.
PMID- 27503450
TI - Imaging the Gambling Brain.
AB - Neuroimaging studies examining the neurobiological basis of gambling disorder
(GD) have increased over the past decade. Functional magnetic resonance imaging
studies during appetitive cue and reward processing tasks demonstrate altered
functioning in frontostriatal brain areas, including the ventral striatum and the
ventromedial prefrontal cortex. Findings suggest differences in how the
anticipation and outcome of rewards are processed in individuals with GD. Future
research requires larger sample sizes and should include appropriate clinical
reference groups. Overall, studies to date highlight a common pathophysiology
between substance-based addictions and GD, the latter offering a unique condition
in which to examine nonchemical factors in addiction.
PMID- 27503449
TI - Psychological and Neurobiological Correlates of Food Addiction.
AB - Food addiction (FA) is loosely defined as hedonic eating behavior involving the
consumption of highly palatable foods (ie, foods high in salt, fat, and sugar) in
quantities beyond homeostatic energy requirements. FA shares some common
symptomology with other pathological eating disorders, such as binge eating.
Current theories suggest that FA shares both behavioral similarities and
overlapping neural correlates to other substance addictions. Although
preliminary, neuroimaging studies in response to food cues and the consumption of
highly palatable food in individuals with FA compared to healthy controls have
shown differing activation patterns and connectivity in brain reward circuits
including regions such as the striatum, amygdala, orbitofrontal cortex, insula,
and nucleus accumbens. Additional effects have been noted in the hypothalamus, a
brain area responsible for regulating eating behaviors and peripheral satiety
networks. FA is highly impacted by impulsivity and mood. Chronic stress can
negatively affect hypothalamic-pituitary-adrenal axis functioning, thus
influencing eating behavior and increasing desirability of highly palatable
foods. Future work will require clearly defining FA as a distinct diagnosis from
other eating disorders.
PMID- 27503452
TI - Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics.
AB - Despite reports of apparent benefits, social and political pressure beginning in
the late 1960s effectively banned scientific inquiry into psychedelic substances.
Covert examination of psychedelics persisted through the 1990s; the turn of the
century and especially the past 10 years, however, has seen a resurgent interest
in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines
relevant EEG and brain imaging studies evaluating the effects of psychedelics on
the brain. This chapter also reviews evidence of the use of psychedelics as
adjunct therapy for a number of psychiatric and addictive disorders. In
particular, psychedelics appear to have efficacy in treating depression and
alcohol-use disorders.
PMID- 27503453
TI - Preface.
PMID- 27503451
TI - Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain
Stimulation Treatments for Cocaine-Dependent Individuals.
AB - Cocaine dependence is one of the most difficult substance use disorders to treat.
While the powerful effects of cocaine use on behavior were documented in the 19th
century, it was not until the late 20th century that we realized cocaine use was
affecting brain tissue and function. Following a brief introduction (Section 1),
this chapter will summarize our current knowledge regarding alterations in neural
circuit function typically observed in chronic cocaine users (Section 2) and
highlight an emerging body of literature which suggests that pretreatment limbic
circuit activity may be a reliable predictor of clinical outcomes among
individuals seeking treatment for cocaine (Section 3). Finally, as the field of
addiction research strives to translate this neuroimaging data into something
clinically meaningful, we will highlight several new brain stimulation approaches
which utilize functional brain imaging data to design noninvasive brain
stimulation interventions for individuals seeking treatment for substance
dependence disorders (Section 4).
PMID- 27503454
TI - The Sclerotinia sclerotiorum Slt2 mitogen-activated protein kinase ortholog,
SMK3, is required for infection initiation but not lesion expansion.
AB - Mitogen-activated protein kinases (MAPKs) play a central role in transferring
signals and regulating gene expression in response to extracellular stimuli. An
ortholog of the Saccharomyces cerevisiae cell wall integrity MAPK was identified
in the phytopathogenic fungus Sclerotinia sclerotiorum. Disruption of the S.
sclerotiorum Smk3 gene severely reduced virulence on intact host plant leaves but
not on leaves stripped of cuticle wax. This was attributed to alterations in
hyphal apical dominance leading to the inability to aggregate and form infection
cushions. The mutation also caused loss of the ability to produce sclerotia,
increased aerial hyphae formation, and altered hyphal hydrophobicity and cell
wall integrity. Mutants had slower radial expansion rates on solid media but more
tolerance to elevated temperatures. Loss of the SMK3 cell wall integrity MAPK
appears to have impaired the ability of S. sclerotiorum to sense its surrounding
environment, leading to misregulation of a variety of functions. Many of the
phenotypes were similar to those observed in S. sclerotiorum adenylate cyclase
and SMK1 MAPK mutants, suggesting that these signaling pathways co-regulate
aspects of fungal growth, physiology, and pathogenicity.
PMID- 27503455
TI - Corrigendum to "High diversity of beta-lactamases in the General Hospital Vienna
verified by whole genome sequencing and statistical analysis" [Infect. Genet.
Evol., Oct.;27 (2014) 408-417].
PMID- 27503456
TI - Discovery of potential prognostic long non-coding RNA biomarkers for predicting
the risk of tumor recurrence of breast cancer patients.
AB - Deregulation of long non-coding RNAs (lncRNAs) expression has been proven to be
involved in the development and progression of cancer. However, expression
pattern and prognostic value of lncRNAs in breast cancer recurrence remain
unclear. Here, we analyzed lncRNA expression profiles of breast cancer patients
who did or did not develop recurrence by repurposing existing microarray datasets
from the Gene Expression Omnibus database, and identified 12 differentially
expressed lncRNAs that were closely associated with tumor recurrence of breast
cancer patients. We constructed a lncRNA-focus molecular signature by the risk
scoring method based on the expression levels of 12 relapse-related lncRNAs from
the discovery cohort, which classified patients into high-risk and low-risk
groups with significantly different recurrence-free survival (HR = 2.72, 95%
confidence interval 2.07-3.57; p = 4.8e-13). The 12-lncRNA signature also
represented similar prognostic value in two out of three independent validation
cohorts. Furthermore, the prognostic power of the 12-lncRNA signature was
independent of known clinical prognostic factors in at least two cohorts.
Functional analysis suggested that the predicted relapse-related lncRNAs may be
involved in known breast cancer-related biological processes and pathways. Our
results highlighted the potential of lncRNAs as novel candidate biomarkers to
identify breast cancer patients at high risk of tumor recurrence.
PMID- 27503457
TI - Preselection of A- and B- modified d-homo lactone and d-seco androstane
derivatives as potent compounds with antiproliferative activity against breast
and prostate cancer cells - QSAR approach and molecular docking analysis.
AB - The problem with trial-and-error approach in organic synthesis of targeted
anticancer compounds can be successfully avoided by computational modeling of
molecules, docking studies and chemometric tools. It has been proven that A- and
B- modified d-homo lactone and d-seco androstane derivatives are compounds with
significant antiproliferative activity against estrogen-independent breast
adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells
(AR-, PC-3). This paper presents the quantitative structure-activity relationship
(QSAR) models based on artificial neural networks (ANNs) which are able to
predict whether d-homo lactone and/or d-seco androstane-based compounds will
express antiproliferative activity against breast cancer cells (MDA-MB-231) or
not. Also, the present paper describes the molecular docking study of 3beta
acetoxy-5alpha,6alpha-epoxy- (3) and 6alpha,7alpha-epoxy-1,4-dien-3-one (24) d
homo lactone androstane derivatives, as well as 4-en-3-one (15) d-seco androstane
derivative, which are compounds with strong or moderate antiproliferative
activity against prostate cancer cells (PC-3), and compares them with
commercially available medicament for prostate cancer - abiraterone. The obtained
promising results can be used as guidelines in further syntheses of novel d-homo
lactone and d-seco androstane derivatives with antiproliferative activity against
breast and prostate cancer cells.
PMID- 27503458
TI - Nanovesicular liposome-encapsulated hemoglobin (LEH) prevents multi-organ
injuries in a rat model of hemorrhagic shock.
AB - The goals of resuscitation in hemorrhagic shock are to correct oxygen deficit and
to maintain perfusion pressure to the vital organs. We created liposome
encapsulated hemoglobin (LEH) as a nanoparticulate oxygen carrier (216+/-2nm)
containing 7.2g/dl hemoglobin, and examined its ability to prevent the systemic
manifestations of hemorrhagic shock (45% blood loss) in a rat model. We collected
plasma after 6h of shock and LEH resuscitation, and determined the circulating
biomarkers of systemic inflammation and functions of liver, gut, heart, and
kidney. As is typical of the shock pathology, a significant increase in the
plasma levels of cardiac troponin, liver function enzymes, soluble CD163
(macrophage activation), and creatinine, and the liver/gut myeloperoxidase
activity was observed in the hemorrhaged rats. The plasma levels of TNF-alpha, IL
6, IL-1alpha, CINC-1, and IL-22 also increased after hemorrhagic shock. LEH
administration prevented the hemorrhagic shock-induced accumulation of the
markers of injury to the critical organs and pro-inflammatory cytokines. LEH also
decreased the plasma levels of stress hormone corticosterone in hemorrhaged rats.
Although saline also reduced the circulating corticosterone and a few other
tissue injury markers, it was not as effective as LEH in restraining the plasma
levels of creatinine, alanine transaminase, CD163, TNF-alpha, IL-6, and IL
1alpha. These results indicate that resuscitation with nanoparticulate LEH
creates a pro-survival phenotype in hemorrhaged rats, and because of its oxygen
carrying capacity, LEH performs significantly better than saline in hemorrhagic
shock.
PMID- 27503459
TI - Tailoring the mucoadhesive and sustained release characteristics of mesalamine
loaded formulations for local treatment of distal forms of ulcerative colitis.
AB - Direct delivery of sustained therapeutic levels of mesalamine (MS) via rectal
systems to manage distal forms of ulcerative colitis was studied. The High
molecular weight hydroxypropyl methylcellulose (HPMC K4M) polymer was combined
with hydrophilic surfactants to control polymer hydration process allowing
optimization of the mucoadhesive and controlled drug release properties for the
rectal systems. Physical mixtures and granules of MS and HPMC K4M were prepared
and in vitro characterized using scanning electron microscope, differential
scanning calorimetry and X-ray diffraction techniques. Rectal formulations were
prepared utilizing MS-HPMC K4M mixtures in different polyethylene glycol (PEG)
combination bases. The developed rectal formulations were investigated for
physical, mucoadhesion, in-vitro drug release and swelling characteristics.
Results revealed acceptable physical characteristics of the prepared formulations
with good content uniformity and minimum weight variation. Sustained release
patterns of MS form HPMC K4M based formulations were observed. Formulations
prepared using high proportions of the polymer or PEG 400 showed higher extent of
mucoadhesion, swelling and greatly extended drug release time. Efficacy of an
optimized formulation was assessed using the acetic acid induced colitis model in
rats and compared to a reference polymer-free formulation of the drug. Clinical
evaluation included bleeding from rectum, consistency of animal stool and
colon/body weight ratio. Furthermore, histopathological analysis was carried out
to evaluate the degree of inflammation and mucosal damage. Overall results showed
a significant enhancement in the clinical pictures and colon histopathology of
animals treated by the sustained release mucoadhesive formulation compared to the
reference polymer free formulation and the non-treated colitis group.
PMID- 27503460
TI - Novel antibodies to phosphorylated alpha-synuclein serine 129 and NFL serine 473
demonstrate the close molecular homology of these epitopes.
AB - Pathological inclusions containing aggregated, highly phosphorylated (at
serine129) alpha-synuclein (alphaS pSer129) are characteristic of a group of
neurodegenerative diseases termed synucleinopathies. Antibodies to the pSer129
epitope can be highly sensitive in detecting alphaS inclusions in human tissue
and experimental models of synucleinopathies. However, the generation of
extensively specific pSer129 antibodies has been problematic, in some cases
leading to the misinterpretation of alphaS inclusion pathology. One common issue
is cross-reactivity to the low molecular mass neurofilament subunit (NFL)
phosphorylated at Ser473. Here, we generated a series of monoclonal antibodies to
the pSer129 alphaS and pSer473 NFL epitopes. We determined the relative abilities
of the known alphaS kinases, polo-like kinases (PLK) 1, 2 and 3 and casein kinase
(CK) II in phosphorylating NFL and alphaS, while using this information to
characterize the specificity of the new antibodies. NFL can be phosphorylated by
PLK1, 2 and 3 at Ser473; however CKII shows the highest phosphorylation
efficiency and specificity for this site. Conversely, PLK3 is the most efficient
kinase at phosphorylating alphaS at Ser129, but there is overlay in the ability
of these kinases to phosphorylate both epitopes. Antibody 4F8, generated to the
pSer473 NFL epitope, was relatively specific for phosphorylated NFL, however it
could uniquely cross-react with pSer129 alphaS when highly phosphorylated,
further showing the structural similarity between these phospho-epitopes. All of
the new pSer129 antibodies detected pathological alphaS inclusions in human
brains and mouse and cultured cell experimental models of induced
synucleinopathies. Several of these pSer129 alphaS antibodies reacted with the
pSer473 NFL epitope, but 2 clones (LS3-2C2 and LS4-2G12) did not. However, LS3
2C2 demonstrated cross-reactivity with other proteins. Our findings further
demonstrate the difficulties in generating specific pSer129 alphaS antibodies,
but highlights that the use of multiple antibodies, such as those generated here,
can provide a sensitive and accurate assessment of alphaS pathology.
PMID- 27503461
TI - Changes in rubisco, cysteine-rich proteins and antioxidant system of spinach
(Spinacia oleracea L.) due to sulphur deficiency, cadmium stress and their
combination.
AB - Sulphur (S) deficiency, cadmium (Cd) toxicity and their combinations are of wide
occurrence throughout agricultural lands. We assessed the impact of short-term (2
days) and long-term (4 days) applications of cadmium (40 MUg/g soil) on spinach
plants grown on sulphur-sufficient (300 MUM SO42-) and sulphur-deficient (30 MUM
SO42-) soils. Compared with the control (+S and -Cd), oxidative stress was
increased by S deficiency (-S and -Cd), cadmium (+S and +Cd) and their
combination stress (-S and +Cd) in the order of (S deficiency) < (Cd stress) < (S
deficiency and +Cd stress). SDS-PAGE profile of leaf proteins showed a high
vulnerability of rubisco large subunit (RbcL) to S deficiency. Rubisco small
subunit (RbcS) was particularly sensitive to Cd as well as dual stress (+Cd and
S) but increased with Cd in the presence of S. Cysteine content in low molecular
weight proteins/peptide was also affected, showing a significant increase under
cadmium treatment. Components of ascorbate-glutathione antioxidant system altered
their levels, showing the maximum decline in ascorbate (ASA), dehydroascorbate
(DHA), total ascorbate (ASA + DHA, hereafter TA), glutathione (GSH) and total
glutathione (GSH + GSSG, hereafter TG) under S deficiency. However, total
ascorbate and total glutathione increased, besides a marginal increase in their
reduced and oxidized forms, when Cd was applied in the presence of sufficient S.
Sulphur supply also helped in increasing the activity of superoxide dismutase
(SOD), ascorbate peroxidase (APX), glutathione reductase (GR) and catalase (CAT)
under Cd stress. However, their activity suffered by S deficiency and by Cd
stress during S deficiency. Each stress declined the contents of soluble protein
and photosynthetic pigments; the highest decline in contents of protein and
pigments occurred under S deficiency and dual stress respectively. The fresh and
dry weights, although affected adversely by every stress, declined most under
dual stress. It may be concluded that an optimal level of S is required during Cd
stress for better response of SOD, APX, GR and CAT activity, as well as synthesis
of cysteine. RbcS is as highly sensitive to S deficiency as RbcL is to Cd stress.
PMID- 27503462
TI - Prosurvival Factors Improve Functional Engraftment of Myogenically Converted
Dermal Cells into Dystrophic Skeletal Muscle.
AB - In Duchenne muscular dystrophy (DMD) and other muscle wasting disorders, cell
therapies are a promising route for promoting muscle regeneration by supplying a
functional copy of the missing dystrophin gene and contributing new muscle
fibers. The clinical application of cell-based therapies is resource intensive,
and it will therefore be necessary to address key limitations that reduce cell
engraftment into muscle tissue. A pressing issue is poor donor cell survival
following transplantation, which in preclinical studies limits the ability to
effectively test the impact of cell-based therapy on whole muscle function. We,
therefore, sought to improve engraftment and the functional impact of in vivo
myogenically converted dermal fibroblasts (dFbs) using a prosurvival cocktail
(PSC) that includes heat shock followed by treatment with insulin-like growth
factor-1, a caspase inhibitor, a Bcl-XL peptide, a KATP channel opener, basic
fibroblast growth factor, Matrigel, and cyclosporine A. Advantages of dFbs
include compatibility with the autologous setting, ease of isolation, and greater
proliferative potential than DMD satellite cells. dFbs expressed tamoxifen
inducible MyoD and carried a mini-dystrophin gene driven by a muscle-specific
promoter. After transplantation into muscles of mdx mice, a 70% reduction in
donor cells was observed by day 5, and a 94% reduction by day 28. However,
treatment with PSC gave a nearly three-fold increase in donor cells in early
engraftment, and greatly increased the number of donor-contributed muscle fibers
and total engrafted area in transplanted muscles. Furthermore, dystrophic muscles
that received dFbs with PSC displayed reduced injury with eccentric contractions
and an increase in maximum isometric force. Thus, enhancing survival of myogenic
cells increases engraftment and improves structure and function of dystrophic
muscle.
PMID- 27503463
TI - [S2e guidelines "Gouty arthritis - specialist"].
PMID- 27503464
TI - A meta-analysis of the social communication questionnaire: Screening for autism
spectrum disorder.
AB - The current meta-analysis examines the previous research on the utility of the
Social Communication Questionnaire as a screening instrument for autism spectrum
disorder. Previously published reports have highlighted the inconsistencies
between Social Communication Questionnaire-screening results and formal autism
spectrum disorder diagnoses. The variations in accuracy resulted in some
researchers questioning the validity of the Social Communication Questionnaire.
This study systematically examined the accuracy of the Social Communication
Questionnaire as a function of the methodological decisions made by researchers
screening for autism spectrum disorder over the last 15 years. Findings from this
study suggest that the Social Communication Questionnaire is an acceptable
screening instrument for autism spectrum disorder (area under the curve = 0.885).
Variations in methodological decisions, however, greatly influenced the accuracy
of the Social Communication Questionnaire in screening for autism spectrum
disorder. Of these methodological variations, using the Current instead of the
Lifetime version of the Social Communication Questionnaire resulted in the
largest detrimental effect ( d = -3.898), followed by using the Social
Communication Questionnaire with individuals younger than 4 years of age ( d =
2.924) and relying upon convenience samples ( d = -4.828 for clinical samples,
2.734 for convenience samples, and -1.422 for community samples). Directions for
future research and implications for using the Social Communication Questionnaire
to screen for autism spectrum disorder are discussed.
PMID- 27503465
TI - Equivalence of symptom dimensions in females and males with autism.
AB - This study investigated equivalence of autism symptom domains in males and
females with autism. Symptom data were obtained from 2643 children and
adolescents with autism spectrum disorder (352 females, 2291 males; age range = 4
17 years) included in the Simons Simplex Collection. Items from the Social
Responsiveness Scale and Autism Diagnostic Interview-Revised were mapped to nine
a priori symptom dimensions. Multi-group confirmatory factor models, including
measurement equivalence and item response theory analyses, examined whether males
and females showed measurement or structural differences in autism symptom
constructs. Results indicated mean differences in restricted interests that were
not due to measurement bias. No other symptom dimension showed evidence of
measurement bias and autism symptom structure was highly similar between males
and females. Future studies are needed to carefully estimate any sex differences
in the content, frequency, or intensity/severity of restricted interests in
females and males.
PMID- 27503466
TI - Monitoring recovery from neuromuscular block using acceleromyography at the
trapezius muscle: problems that must be considered.
PMID- 27503467
TI - Whole-genome regulation analysis of histone H3 lysin 27 trimethylation in
subclinical mastitis cows infected by Staphylococcus aureus.
AB - BACKGROUND: S. aureus is one of the major etiological agents causing bovine
subclinical mastitis. The regulatory effects of H3K27me3 on gene expression in
subclinical S. aureus mastitis cows are unknown. This study aimed to profile
genome-wide transcriptional changes regulated by H3K27me3 in bovine lymphocytes
applied in subclinical S. aureus mastitis cows and healthy controls. RESULTS: A
total of 61 differentially expressed genes (DEGs) were detected in subclinical S.
aureus mastitis cows compared to the healthy controls, of which 25 DEGs are up
regulated and the rest are down-regulated genes in subclinical S.aureus mastitis
cows. The up-regulated genes are mainly involved in the Jak-STAT signaling
pathway, cytokine-cytokine receptor interaction, and T cell receptor-signaling
pathway, while the down-regulated genes are related to metabolism pathways.
Combination analysis of histone methylation and gene expression revealed that
H3K27 trimethylation levels in silent genes were higher in subclinical S. aureus
mastitis cattle than in healthy cows. The key regions of H3K27me3 target genes
related to subclinical S. aureus mastitis were the upstream 2 kb regions of the
DEGs relative to transcription start site (TSS). CONCLUSIONS: The current study
provides a novel insight into the interaction between S. aureus and lymphocytes
in lactating cows by histone H3 methylation regulation. The differentially
expressed genes in bovine lymphocytes regulated by H3K27me3 on upstream 2 kb
regions (IL10, PTX3 and etc.) may relate to S. aureus mastitis susceptibility and
could be considered as key candidate genes for anti- S. aureus mastitis study and
breeding.
PMID- 27503469
TI - Decreased absorption of midazolam in the stomach due to low pH induced by co
administration of Banha-sasim-tang.
AB - OBJECTIVES: Banha-sasim-tang (BST), which consists of seven different herbs, is
one of the most popular herbal formulae for treating gastrointestinal disorders
in Eastern Asia. The commonly used herbal medicine is often co-administered with
other therapeutic drugs, which raises the possibility of herb-drug interactions
and may modify the clinical safety profile of therapeutic drugs. METHODS: We
investigated the potential herb-drug interactions between BST extract and
midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC)
of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and
intraperitoneal administration of MDZ, following oral administration of BST (0.5
and 1 g/kg). RESULTS: It was found that the AUC of MDZ and 1'-OH-MDZ was lower in
case of oral administration of MDZ. Administration of BST extract was not
associated with hepatic cytochrome P450 activity. BST extract induced a strong
reduction in pH and it has been reported that oral mucosal absorption of MDZ is
lower at low pH. The decreased absorption rate of MDZ might be caused by the
ingredients of BST and may not be related to other factors such as increased
excretion of MDZ by P-glycoprotein. CONCLUSIONS: The altered pharmacokinetics of
midazolam caused by co-administration with BST in vivo could be attributed to a
decrease in pH and subsequent reduction of MDZ absorption rate.
PMID- 27503468
TI - Growing Out of Stress: The Role of Cell- and Organ-Scale Growth Control in Plant
Water-Stress Responses.
AB - Water is the most limiting resource on land for plant growth, and its uptake by
plants is affected by many abiotic stresses, such as salinity, cold, heat, and
drought. While much research has focused on exploring the molecular mechanisms
underlying the cellular signaling events governing water-stress responses, it is
also important to consider the role organismal structure plays as a context for
such responses. The regulation of growth in plants occurs at two spatial scales:
the cell and the organ. In this review, we focus on how the regulation of growth
at these different spatial scales enables plants to acclimate to water-deficit
stress. The cell wall is discussed with respect to how the physical properties of
this structure affect water loss and how regulatory mechanisms that affect wall
extensibility maintain growth under water deficit. At a higher spatial scale, the
architecture of the root system represents a highly dynamic physical network that
facilitates access of the plant to a heterogeneous distribution of water in soil.
We discuss the role differential growth plays in shaping the structure of this
system and the physiological implications of such changes.
PMID- 27503470
TI - Foraging Behavior Interactions Between Two non-Native Social Wasps, Vespula
germanica and V. vulgaris (Hymenoptera: Vespidae): Implications for Invasion
Success?
AB - Vespula vulgaris is an invasive scavenging social wasp that has very recently
arrived in Patagonia (Argentina), a territory previously invaded - 35 yrs earlier
- by another wasp, Vespula germanica Although V. vulgaris wasps possess features
that could be instrumental in overcoming obstacles through several invasion
stages, the presence of preestablished populations of V. germanica could affect
their success. We studied the potential role played by V. germanica on the
subsequent invasion process of V. vulgaris wasps in Patagonia by focusing on the
foraging interaction between both species. This is because food searching and
exploitation are likely to overlap strongly among Vespula wasps. We carried out
choice tests where two types of baits were presented in a pairwise manner. We
found experimental evidence supporting the hypothesis that V. germanica and V.
vulgaris have an asymmetrical response to baits with stimuli simulating the
presence of each other. V. germanica avoided baits with either visual or
olfactory cues indicating the V. vulgaris presence. However, V. vulgaris showed
no preference between baits with or lacking V. germanica stimuli. These results
suggest that the presence of an established population of V. germanica may not
contribute to added biotic resistance to V. vulgaris invasion.
PMID- 27503471
TI - Stability and localization of 14-3-3 proteins are involved in salt tolerance in
Arabidopsis.
AB - KEY MESSAGE: Salt stress induces the degradation of 14-3-3 proteins, and affects
the localization of 14-3-3 lambda. Both the modulation of 14-3-3 protein
stability and the subcellular localization of these proteins are involved in salt
tolerance in plants. Salt tolerance in plants is regulated by multiple signaling
pathways, including the salt overly sensitive (SOS) pathway, of which the SOS2
protein is a key component. SOS2 is activated under salt stress to enhance salt
tolerance in plants. We previously identified 14-3-3 lambda and kappa as
important regulators of salt tolerance. Both proteins interact with SOS2 to
inhibit its kinase activity under normal growth conditions. In response to salt
stress, 14-3-3 proteins dissociate from SOS2, releasing its activity and
activating the SOS pathway to confer salt tolerance (Zhou et al. Plant Cell
26:1166-1182, 2014). Here we report that salt stress promotes the degradation of
14-3-3 lambda and kappa, at least in part via the actions of SOS3-like calcium
binding protein 8/calcineurin-B-like10, and also decreases the plasma membrane
(PM) localization of 14-3-3 lambda. Salt stress also partially represses the
interaction of SOS2 and 14-3-3 lambda at the PM, but activates PM-localized SOS2.
Together, these results suggest that, in plants, both the modulation of 14-3-3
stability and the subcellular localization of these proteins in response to salt
stress are important for SOS2 activation and salt tolerance. These data provide
new insights into the biological roles of 14-3-3 proteins in modulating salt
tolerance.
PMID- 27503472
TI - GH32 family activity: a topological approach through protein contact networks.
AB - KEY MESSAGE: The application of Protein Contact Networks methodology allowed to
highlight a novel response of border region between the two domains to substrate
binding. Glycoside hydrolases (GH) are enzymes that mainly hydrolyze the
glycosidic bond between two carbohydrates or a carbohydrate and a non
carbohydrate moiety. These enzymes are involved in many fundamental and diverse
biological processes in plants. We have focused on the GH32 family, including
enzymes very similar in both sequence and structure, each having however clear
specificities of substrate preferences and kinetic properties. Structural and
topological differences among proteins of the GH32 family have been here
identified by means of an emerging approach (Protein Contact network, PCN) based
on the formalization of 3D structures as contact networks among amino-acid
residues. The PCN approach proved successful in both reconstructing the already
known functional domains and in identifying the structural counterpart of the
properties of GH32 enzymes, which remain uncertain, like their allosteric
character. The main outcome of the study was the discovery of the activation upon
binding of the border (cleft) region between the two domains. This reveals the
allosteric nature of the enzymatic activity for all the analyzed forms in the
GH32 family, a character yet to be highlighted in biochemical studies.
Furthermore, we have been able to recognize a topological signature (graph
energy) of the different affinity of the enzymes towards small and large
substrates.
PMID- 27503473
TI - Assessing the reproducibility of exome copy number variations predictions.
AB - BACKGROUND: Reproducibility is receiving increased attention across many domains
of science and genomics is no exception. Efforts to identify copy number
variations (CNVs) from exome sequence (ES) data have been increasing. Many
algorithms have been published to discover CNVs from exomes and a major challenge
is the reproducibility in other datasets. Here we test exome CNV calling
reproducibility under three conditions: data generated by different sequencing
centers; varying sample sizes; and varying capture methodology. METHODS: Four CNV
tools were tested: eXome Hidden Markov Model (XHMM), Copy Number Inference From
Exome Reads (CoNIFER), EXCAVATOR, and Copy Number Analysis for Targeted
Resequencing (CONTRA). To examine the reproducibility, we ran the callers on four
datasets, varying sample sizes of N = 10, 30, 75, 100, 300, and data with
different capture methodology. We examined the false negative (FN) calls and
false positive (FP) calls for potential limitations of the CNV callers. The
positive predictive value (PPV) was measured by checking the CNV call concordance
against single nucleotide polymorphism array. RESULTS: Using independently
generated datasets, we examined the PPV for each dataset and observed wide range
of PPVs. The PPV values were highly data dependent (p <0.001). For the sample
sizes and capture method analyses, we tested the callers in triplicates. Both
analyses resulted in wide ranges of PPVs, even for the same test. Interestingly,
negative correlations between the PPV and the sample sizes were observed for
CoNIFER (rho = -0.80). Further examination of FN calls showed that 44 % of these
were missed by all callers and were attributed to the CNV size (46 % spanned <=3
exons). Overlap of the FP calls showed that FPs were unique to each caller,
indicative of algorithm dependency. CONCLUSIONS: Our results demonstrate that
further improvements in CNV callers are necessary to improve reproducibility and
to include wider spectrum of CNVs (including the small CNVs). These CNV callers
should be evaluated on multiple independent, heterogeneously generated datasets
of varying size to increase robustness and utility. These approaches to the
evaluation of exome CNV are essential to support wide utility and applicability
of CNV discovery in exome studies.
PMID- 27503474
TI - Effects of typhoid vaccine on inflammation and sleep in healthy participants: a
double-blind, placebo-controlled, crossover study.
AB - RATIONALE: An increasing body of evidence links the occurrence of sleep
continuity disturbances with increased inflammation and both sleep disturbances
and inflammation are associated with clinical depression. Typhoid vaccination
results in a mild inflammatory response that significantly increases levels of
the proinflammatory cytokine, interleukin (IL)-6. OBJECTIVES: The present
exploratory study aimed to enhance our understanding of the link between
inflammation, sleep and depression by examining the effects of typhoid vaccine on
the sleep polysomnogram. METHODS: We studied the effects of a single injection of
typhoid polysaccharide vaccine and placebo (saline solution) on sleep in 16
healthy male and female participants aged 20-38 years, sleeping at home in a
randomized, double-blind, balanced order, crossover design. Subjective measures
of mood, sleep and adverse effects were elicited and plasma samples analysed for
IL-6 levels. RESULTS: IL-6 levels (in picogramme per millilitre) significantly
increased 2 h post vaccine compared to placebo (0.90 vs 0.53, p = 0.026, r =
0.55). Relative to placebo, typhoid vaccination produced significant impairment
in several measures of sleep continuity. Total sleep time (in minute) (426.1 vs
410.7, p = 0.005, r = 0.62) and sleep efficiency percent (94.3 vs 91.5, p =
0.007, r = 0.65) were decreased; with increases in wake after sleep onset (in
minute) (25.5 vs 38.8, p = 0.007,r = 0.65), total wake (in minute) (34.9 vs 50.3,
p = 0.005,r = 0.67), sleep stage transitions (155.9 vs 173.1, p = 0.026, r =
0.56), number of awakenings (27.2 vs 36.1, p = 0.007, r = 0.64) and awakening
index (3.8 vs 5.3, p = 0.005, r = 0.67) (means, significance level and effect
size). CONCLUSIONS: Inflammatory mechanisms may underlie the impairment in sleep
efficiency which is a hallmark of major depression. Because impaired sleep is
also a predictor of major depression, there may be a role for suitable anti
inflammatory approaches in strategies designed to prevent the onset of
depression. ClinicalTrials.gov ( http://www.clinicaltrials.gov ): NCT02628054.
PMID- 27503475
TI - Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats.
AB - RATIONALE: The appetite-stimulating properties of cannabis are well documented
and have been predominantly attributed to the hyperphagic activity of the
psychoactive phytocannabinoid, ?(9)-tetrahydrocannabinol (?(9)-THC). However, we
have previously shown that a cannabis extract devoid of ?(9)-THC still stimulates
appetite, indicating that other phytocannabinoids also elicit hyperphagia. One
possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG),
which has affinity for several molecular targets with known involvement in the
regulation of feeding behaviour. OBJECTIVES: The objective of the study was to
assess the effects of CBG on food intake and feeding pattern microstructure.
METHODS: Male Lister hooded rats were administered CBG (30-120 mg/kg, per ora
(p.o.)) or placebo and assessed in open field, static beam and grip strength
tests to determine a neuromotor tolerability profile for this cannabinoid.
Subsequently, CBG (at 30-240 mg/kg, p.o.) or placebo was administered to a
further group of pre-satiated rats, and hourly intake and meal pattern data were
recorded over 2 h. RESULTS: CBG produced no adverse effects on any parameter in
the neuromotor tolerability test battery. In the feeding assay, 120-240 mg/kg CBG
more than doubled total food intake and increased the number of meals consumed,
and at 240 mg/kg reduced latency to feed. However, the sizes or durations of
individual meals were not significantly increased. CONCLUSIONS: Here, we
demonstrate for the first time that CBG elicits hyperphagia, by reducing latency
to feed and increasing meal frequency, without producing negative neuromotor side
effects. Investigation of the therapeutic potential of CBG for conditions such as
cachexia and other disorders of eating and body weight regulation is thus
warranted.
PMID- 27503477
TI - The incredible shrinking problem of the device patient.
PMID- 27503476
TI - Changes in symptoms of asthma and rhinitis by sensitization status over ten years
in a cohort of young Chilean adults.
AB - BACKGROUND: We investigated the net changes in prevalence of symptoms of asthma
and rhinitis over 10 years in a cohort of young by baseline sensitization status.
METHODS: One thousand one hundred ninety three Chilean adults subjects aged 22-28
living in a semi-rural area of central Chile answered a lifestyle and the
European Community Respiratory Health Survey (ECRHS) questionnaires. Bronchial
hyper-responsiveness (BHR) and skin prick test (SPT) to eight allergens were
measured at baseline in 2001. Ten years later, 772 participants completed the
questionnaires again. Estimates of adjusted net changes in prevalence of symptoms
by sensitization status at baseline and association between sensitization status
at baseline and respiratory symptoms ten years later were assessed. RESULTS: A
quarter of the participants were sensitized to at least one allergen in 2001.
Prevalence of wheeze had a net change per year of -0.37 % (95 % Confidence
Interval -0.71 to 0.02 %; p = 0.067). Self-reported nasal allergies in the last
12 months increased by 0.83 % per year (95 % CI 0.49 to 1.17 %; p < 0.001). Those
sensitized to either cat fur (OR 1.76; CI 1.01 to 3.05), cockroach, (OR 2.09;
1.13 to 3.86) blend of grass and pollens (1.78; 95 % CI 1.08 to 2.92), or weeds
(OR 1.77; 95 % CI 1.01 to 3.12) in 2001 were more likely to have wheeze in the
last 12 months 10 years later. CONCLUSION: Symptoms of asthma remained stable or
slightly changed over 10 years in adults, whilst rhinitis and nasal allergies
greatly increased. Being sensitized to at least one allergen is a risk factor for
persistent symptoms of asthma and rhinitis, but not for determining net changes
of symptoms over time. The underlying causes for the contrasting trends between
asthma and nasal allergy are unknown.
PMID- 27503478
TI - Reply to the Editor- Bipolar left ventricular pacing is associated with
significant reduction in heart failure or death in CRT-D patients with LBBB.
PMID- 27503479
TI - To the Editor- Bipolar left ventricular pacing is associated with significant
reduction in heart failure or death in CRT-D patients with LBBB.
PMID- 27503480
TI - Catheter ablation using the third-generation cryoballoon provides an enhanced
ability to assess time to pulmonary vein isolation facilitating the ablation
strategy: Short- and long-term results of a multicenter study.
AB - BACKGROUND: Limited data exist on cryoablation of atrial fibrillation (Cryo-AF)
using the newly available third-generation (Arctic Front Advance-Short Tip [AFA
ST]) cryoballoon. OBJECTIVE: In this multicenter study, we evaluated the safety
and efficacy of Cryo-AF using the AFA-ST vs the second-generation (Arctic Front
Advance [AFA]) cryoballoon. METHODS: We examined the procedural safety and
efficacy and the short- and long-term clinical outcomes associated with a first
time Cryo-AF performed in 355 consecutive patients (254/355 [72%] with paroxysmal
AF), using either the AFA-ST (n = 102) or the AFA (n = 253) cryoballoon
catheters. RESULTS: Acute isolation was achieved in 99.6% of all pulmonary veins
(PVs) (AFA-ST: 100% vs AFA: 99.4%; P = .920). Time to pulmonary vein isolation
was recorded in 89.2% of PVs using AFA-ST vs 60.2% using AFA (P < .001). PVs
targeted using AFA-ST required fewer applications (1.6 +/- 0.8 vs 1.7 +/- 0.8; P
= .023), whereas there were no differences in the balloon nadir temperature (AFA
ST: -47.0 degrees C +/- 7.3 degrees C vs AFA: -47.5 degrees C +/- 7.8 degrees C;
P = .120) or thaw time (AFA-ST: 41 +/- 24 seconds vs AFA: 44 +/- 28 seconds; P =
.056). However, AFA-ST was associated with shorter left atrial dwell time (43 +/-
5 minutes vs 53 +/- 16 minutes; P < .001) and procedure time (71 +/- 11 minutes
vs 89 +/- 25 minutes; P < .001). Furthermore, Cryo-AF using AFA-ST was completed
more frequently by "single-shot" PV ablation (27.4% vs 20.2%; P = .031).
Persistent phrenic nerve palsy (AFA-ST: 0% vs AFA: 0.8%; P = .507) and procedure
related adverse events (AFA-ST: 1.0% vs AFA: 1.6%; P = .554) were similar, as was
the freedom from recurrent atrial arrhythmias at 10 months of follow-up (AFA-ST:
81.8% vs AFA: 79.9%; P = .658). CONCLUSION: Cryo-AF using the AFA-ST cryoballoon
offers an enhanced ability to assess time to pulmonary vein isolation, allowing
for fewer cryoapplications and shorter left atrial dwell time and procedure time.
Consequently, this allowed for procedural completion more frequently using a
"single-shot" PV ablation with equivalent safety and efficacy.
PMID- 27503481
TI - Patellar height assessment in total knee arthroplasty: a new method.
AB - INTRODUCTION: We described in 1981 a method to evaluate patellar height in normal
and symptomatic knees on sagittal X-ray view. This index is a frequently used
method, yet it is not suitable after a total knee arthroplasty (TKA). MATERIAL
AND METHOD: The original method measures the distance between the distal margin
of the articular surface of the patella (point A) and the anterosuperior angle of
the tibial plateau (point T), then the length of the patellar articular surface
(AP). The index is AT/AP ratio (normal values range from 0.8 to 1.2). After TKA,
the T landmark is no longer available, so we must define a new T' landmark. This
point is situated at the intersection between the line perpendicular to the
tibial posterior cortex elevated at the tip of the fibular head and the tibial
anterior cortex. This remarkable landmark can be identified before and after TKA,
with a new relative index AT'/AP ratio. This modified method allows the
comparison of patella height before and after TKA. RESULTS: We have used this
modified index with the collaboration of several authors during the testing of
different models of TKA, with an accurate reproducibility. Repeatability (usually
called intra-observer reliability) was good, with intra-class correlation
coefficients (ICCs) between 0.58 and 0.75 among the observers. Reproducibility
(usually called inter-observer reliability) was also considered as good, with ICC
ranging from 0.64 to 0.72. DISCUSSION: Patella height measurement has to be
assessed with the original method (AT/AP) to detect patella infera that could
influence the surgical approach. The correlation between original and modified
indexes has to be assessed. The modification of patella height after TKA could be
evaluated through the modified index and compared with functional results.
PMID- 27503482
TI - Ingenol Disoxate: A Novel 4-Isoxazolecarboxylate Ester of Ingenol with Improved
Properties for Treatment of Actinic Keratosis and Other Non-Melanoma Skin
Cancers.
AB - INTRODUCTION: Ingenol mebutate gel (Picato(r), LEO Pharma A/S) is approved for
the field treatment of actinic keratosis and is characterized by high sustained
clearance of actinic lesions. The inherent propensity of ingenol mebutate towards
chemical rearrangement necessitates refrigeration of the final product. We sought
to identify novel ingenol derivatives with enhanced chemical stability and
similar or improved in vitro potency and in vivo efficacy. METHODS: A number of
ingenol esters were synthesized with full regiocontrol from ingenol. Chemical
stability was determined in aqueous buffer at physiological pH and hydroalcoholic
gel at lower pH. Acute cytotoxicity was determined in HeLa or HSC-5 cells.
Keratinocyte proliferation, viability and caspase 3/7 activation was measured in
primary epidermal keratinocytes. Relative gene expression levels were determined
by real-time quantitative PCR. Evaluation of in vivo tumor ablating potential was
performed in the murine B16 melanoma mouse model and in the UV-induced skin
carcinogenesis model in hairless SKH-1 mice following topical treatment for two
consecutive days with test compounds formulated at 0.1% in a hydroalcoholic gel.
RESULTS: This work resulted in the identification of ingenol disoxate (LEO 43204)
displaying increased stability in a clinically relevant formulation and in
aqueous buffer with minimal pH-dependent acyl migration degradation. Ingenol
disoxate exhibited a significantly higher cytotoxic potency relative to ingenol
mebutate. Likewise, cell growth arrest in normal human keratinocyte was more
potently induced by ingenol disoxate, which was accompanied by protein kinase C
dependent transcription of markers of keratinocyte differentiation. Most notably,
ingenol disoxate possessed a superior antitumor effect in a B16 mouse melanoma
model and significantly increased median survival time relative to ingenol
mebutate. A significant effect on tumor ablation was also observed in a murine
model of ultraviolet irradiation-induced skin carcinogenesis. CONCLUSION: These
data illustrate that the favorable in vitro and in vivo pharmacological
properties driving ingenol mebutate efficacy are either preserved or improved in
ingenol disoxate. In combination with improved chemical stability to potentially
facilitate storage of the final product at ambient temperatures, these features
support further development of ingenol disoxate as a convenient and efficacious
treatment modality of non-melanoma skin cancers. FUNDING: LEO Pharma A/S.
PMID- 27503484
TI - Fermentation of de-oiled algal biomass by Lactobacillus casei for production of
lactic acid.
AB - De-oiled algal biomass (algal cake) generated as waste byproduct during algal
biodiesel production is a promising fermentable substrate for co-production of
value-added chemicals in biorefinery systems. We explored the ability of
Lactobacillus casei 12A to ferment algal cake for co-production of lactic acid.
Carbohydrate and amino acid availability were determined to be limiting
nutritional requirements for growth and lactic acid production by L. casei. These
nutritional requirements were effectively addressed through enzymatic hydrolysis
of the algal cake material using alpha-amylase, cellulase (endo-1,4-beta-D
glucanase), and pepsin. Results confirm fermentation of algal cake for production
of value-added chemicals is a promising avenue for increasing the overall cost
competiveness of the algal biodiesel production process.
PMID- 27503483
TI - Comparability of automated human induced pluripotent stem cell culture: a pilot
study.
AB - Consistent and robust manufacturing is essential for the translation of cell
therapies, and the utilisation automation throughout the manufacturing process
may allow for improvements in quality control, scalability, reproducibility and
economics of the process. The aim of this study was to measure and establish the
comparability between alternative process steps for the culture of hiPSCs.
Consequently, the effects of manual centrifugation and automated non
centrifugation process steps, performed using TAP Biosystems' CompacT SelecT
automated cell culture platform, upon the culture of a human induced pluripotent
stem cell (hiPSC) line (VAX001024c07) were compared. This study, has demonstrated
that comparable morphologies and cell diameters were observed in hiPSCs cultured
using either manual or automated process steps. However, non-centrifugation hiPSC
populations exhibited greater cell yields, greater aggregate rates, increased
pluripotency marker expression, and decreased differentiation marker expression
compared to centrifugation hiPSCs. A trend for decreased variability in cell
yield was also observed after the utilisation of the automated process step. This
study also highlights the detrimental effect of the cryopreservation and thawing
processes upon the growth and characteristics of hiPSC cultures, and demonstrates
that automated hiPSC manufacturing protocols can be successfully transferred
between independent laboratories.
PMID- 27503485
TI - Implementation and analysis of temperature control strategies for outdoor
photobiological hydrogen production.
AB - For outdoor photobiological hydrogen production, the effective control of
temperature in photobioreactors is a challenge. In this work, an internal cooling
system for outdoor tubular photobioreactors was designed, built, and tested. The
temperatures in the reactors with bacteria were consistently higher than those
without bacteria, and were also strongly influenced by solar irradiation and
ambient air temperature. The cooling protocol applied successfully kept the
reactor temperatures below the threshold limit (38 degrees C) required for the
bioprocess and provided a uniform distribution of temperature along the reactor
tube length. The biomass growth and hydrogen production were similar in the
reactors cooled co-currently and counter-currently. The biomass growth rate was
0.1 l/h, the maximum hydrogen production rate was 1.28 mol/m3/h, and the overall
hydrogen yield obtained was 20 %. The change in the biomass was fitted using the
logistic model while cumulative hydrogen production was fitted using the modified
Gompertz equation.
PMID- 27503486
TI - Hydrophobic adsorption in ionic medium improves the catalytic properties of
lipases applied in the triacylglycerol hydrolysis by synergism.
AB - It is known that lipases may have their catalytic properties improved by the
action of some salts or by the adsorption on hydrophobic supports. However, what
we present in this work is more than that: we evaluate the combination of these
two factors of hyperactivation of lipases from Acremonium-like ROG 2.1.9, a study
that has not been done so far. This work proves that a synergistic effect occurs
when the lipases are immobilized on hydrophobic supports at the presence of
sodium chloride and are applied in triacylglycerol hydrolysis. This assay made it
possible to achieve the highest hyperactivation of 500 % with the lipases
immobilized on Phenyl-Sepharose and applied with 0.1 M of sodium chloride.
Besides this positive effect on enzyme activity, the use of these two factors led
to the thermal stability increasing of the immobilized lipases. For this
derivative, the recovered activity was approximately 85 % after 6 h incubated at
55 degrees C and 1.0 M of the sodium chloride against 50 % of the same
derivative without this salt. Furthermore, others assays were performed to prove
the evidences about the synergistic effect, showing a promising method to improve
the catalytic properties of the lipases from Acremonium-like ROG 2.1.9.
PMID- 27503487
TI - Cobalt separation by Alphaproteobacterium MTB-KTN90: magnetotactic bacteria in
bioremediation.
AB - Bioremediation of toxic metals by magnetotactic bacteria and magnetic separation
of metal-loaded magnetotactic bacteria are of great interest. This bioprocess
technique is rapid, efficient, economical, and environmentally friendly. In this
study, cobalt removal potential of a novel isolated magnetotactic bacterium
(Alphaproteobacterium MTB-KTN90) as a new biosorbent was investigated. The
effects of various environmental parameters in the cobalt removal and the
technique of magnetic separation of cobalt-loaded bacterial cells were studied.
Cobalt removal by MTB-KTN90 was very sensitive to pH solution; higher biosorption
capacity was observed around pH 6.5-7.0. When biomass concentration increased
from 0.009 to 0.09 g/l, the biosorption efficiency increased from 13.87 % to
19.22 %. The sorption of cobalt by MTB-KTN90 was rapid during the first 15 min
(859.17 mg/g dry weight). With the increasing of cobalt concentrations from 1 to
225 mg/l, the specific cobalt uptake increased. Maximum cobalt removal (1160.51
+/- 15.42 mg/g dry weight) took place at optimum conditions; pH 7.0 with initial
cobalt concentration of 115 mg/l at 60 min by 0.015 g/l of dry biomass. The
results showed maximum values for constants of Langmuir and Freundlich models so
far. The biosorption mechanisms were studied with FTIR, PIXE, and FESEM analysis.
Cobalt-loaded MTB-KTN90 had ability to separate from solution by a simple
magnetic separator. Magnetic response in MTB-KTN90 is due to the presence of
unique intracellular magnetic nanoparticles (magnetosomes). The orientation
magnetic separation results indicated that 88.55 % of cobalt was removed from
solution. Consequently, Alphaproteobacterium MTB-KTN90 as a new biosorbent opens
up good opportunities for the magnetic removal of cobalt from the polluted
aquatic environments.
PMID- 27503488
TI - Removal of pigments from molasses wastewater by combining micro-electrolysis with
biological treatment method.
AB - Pigments in molasses wastewater (MWW) effluent, such as melanoidins, were
considered as kinds of the most recalcitrant and hazardous colorant contaminants
to the environment. In this study, de-coloring the MWW by a synergistic
combination of micro-electrolysis with bio-treatment was performed. Aiming to a
high de-colorization yield, levels of nutrition source supplies, MWW dilution
ratio, and micro-electrolysis reaction time were optimized accordingly. For a
diluted (50 %, v/v) MWW, an maximum overall de-colorization yield (97.1 +/- 0.5
%, for absorbance at 475 nm) was achieved through the bio-electrolysis treatment.
In electrolysis bio-treatment, the positive effect of micro-electrolysis was also
revealed by a promoted growth of fungal biomass as well as activities of
ligninolytic enzymes. Activities of lignin peroxidase, manganese peroxidase, and
laccase were promoted by 111.2, 103.9, and 7.7 %, respectively. This study also
implied that the bio-treatment and the micro-electrolysis had different
efficiencies on removal of pigments with distinct polarities.
PMID- 27503489
TI - Computation of a high-resolution MRI 3D stereotaxic atlas of the sheep brain.
AB - The sheep model was first used in the fields of animal reproduction and
veterinary sciences and then was utilized in fundamental and preclinical studies.
For more than a decade, magnetic resonance (MR) studies performed on this model
have been increasingly reported, especially in the field of neuroscience. To
contribute to MR translational neuroscience research, a brain template and an
atlas are necessary. We have recently generated the first complete T1-weighted
(T1W) and T2W MR population average images (or templates) of in vivo sheep
brains. In this study, we 1) defined a 3D stereotaxic coordinate system for
previously established in vivo population average templates; 2) used deformation
fields obtained during optimized nonlinear registrations to compute nonlinear
tissues or prior probability maps (nlTPMs) of cerebrospinal fluid (CSF), gray
matter (GM), and white matter (WM) tissues; 3) delineated 25 external and 28
internal sheep brain structures by segmenting both templates and nlTPMs; and 4)
annotated and labeled these structures using an existing histological atlas. We
built a quality high-resolution 3D atlas of average in vivo sheep brains linked
to a reference stereotaxic space. The atlas and nlTPMs, associated with
previously computed T1W and T2W in vivo sheep brain templates and nlTPMs, provide
a complete set of imaging space that are able to be imported into other imaging
software programs and could be used as standardized tools for neuroimaging
studies or other neuroscience methods, such as image registration, image
segmentation, identification of brain structures, implementation of recording
devices, or neuronavigation. J. Comp. Neurol. 525:676-692, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27503490
TI - Low-dose aspirin or other nonsteroidal anti-inflammatory drug use and prostate
cancer risk: a nationwide study.
AB - PURPOSE: Increasing evidence suggests that aspirin use may protect against
prostate cancer. In a nationwide case-control study, using Danish high-quality
registry data, we evaluated the association between the use of low-dose aspirin
or other nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of prostate
cancer. METHODS: We identified 35,600 patients (cases) with histologically
verified prostate cancer during 2000-2012. Cases were matched to 177,992
population controls on age and residence by risk-set sampling. Aspirin and
nonaspirin NSAID exposure was defined by type, estimated dose, duration, and
consistency of use. We used conditional logistic regression to estimate odds
ratios (ORs), with 95 % confidence intervals (CIs), for prostate cancer
associated with low-dose aspirin (75-150 mg) or nonaspirin NSAID use, adjusted
for potential confounders. RESULTS: Use of low-dose aspirin was associated with
an OR for prostate cancer of 0.94 (95 % CI 0.91-0.97). Slightly lower ORs were
seen with increasing cumulative amount, duration, and consistency of low-dose
aspirin use (continuous use, >=5 years: OR 0.89; 95 % CI 0.82-0.97; >=10 years:
OR 0.86; 95 % CI 0.70-1.06). Nonaspirin NSAID use was associated with a slightly
increased OR for prostate cancer (1.13; 95 % CI 1.10-1.15); however, this
association was confined to localized disease and did not vary materially with
amount, duration, or consistency of nonaspirin NSAID use. CONCLUSIONS: Our study
indicates that long-term, consistent low-dose aspirin use may provide modest
protection against prostate cancer. The slightly increased risk of only localized
prostate cancer with nonaspirin NSAID use suggests a noncausal explanation of the
observed association.
PMID- 27503491
TI - The Role of Laparoscopic Radical Hysterectomy in Early-Stage Adenocarcinoma of
the Uterine Cervix.
AB - OBJECTIVE: To compare long-term survival outcomes and patterns of recurrence of
laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in
early-stage cervical adenocarcinoma. METHODS: The medical records of 293 patients
with stage IA2-IIA cervical adenocarcinomas who underwent radical hysterectomy
were retrospectively reviewed. RESULTS: In total, 186 patients underwent LRH and
107 underwent ORH. There was no difference between the two surgery groups in
clinicopathologic characteristics. There were no differences in disease-free
survival (DFS) and overall survival (OS) between the LRH and ORH groups (88.7 vs.
84.1 %, P = 0.725; and 93.0 vs. 86.9 %, P = 0.735) for univariate analysis and
multivariate analysis after adjusting for other significant prognostic factors.
There was no difference in the patterns of recurrence between the two surgery
groups (P = 0.220). The median time interval between surgery and the first
recurrence were 25 months (range, 3-100 months) for LRH group and 14 months
(range, 3-128 months) for ORH group (P = 0.230). The LRH group showed
significantly fewer postoperative complications (P < 0.001), less estimated blood
loss (P < 0.001), faster bowel movement recovery (P < 0.001), shorter
postoperative hospital stay (P < 0.001), and a lower rate of wound dehiscence,
ileus, lymphedema, infected lymphocele, and pelvic abscess (P = 0.004, 0.011,
0.017, and 0.040, respectively). CONCLUSIONS: LRH has comparable survival
outcomes with ORH and did not affect the pattern of recurrence in early-stage
adenocarcinoma of the uterine cervix. The surgical outcomes were more favorable
than ORH.
PMID- 27503492
TI - Time to Treatment: Measuring Quality Breast Cancer Care.
AB - BACKGROUND: To optimize breast cancer care, several organizations have crafted
guidelines to define best practices for treating breast cancer. In addition to
recommended therapies, 'timeliness of treatment' has been proposed as a quality
metric. Our study evaluates time to surgical treatment and its effect on overall
survival (OS). METHODS: The National Cancer Data Base (NCDB) was used to identify
women diagnosed with invasive breast cancer between 2004 and 2012. Time from
diagnosis to surgical treatment was calculated and grouped according to
predetermined time intervals. Univariate and multivariate Cox proportional hazard
models were used to assess patient and treatment factors related to OS. RESULTS:
Overall, 420,792 patients initially treated with surgery were identified.
Increased time to surgical treatment >12 weeks was associated with decreased OS
[hazard ratio (HR) 1.14, 95 % confidence interval (CI) 1.09-1.20]. When
stratified by pathologic stage, stage I patients treated at 8 to <12 weeks (HR
1.07, 95 % CI 1.02-1.13) and >12 weeks (HR 1.19, 95 % CI 1.11-1.28), as well as
stage II patients treated at >12 weeks (HR 1.16, 95 % CI 1.08-1.25), had
decreased OS compared with patients treated at <4 weeks. Other variables
associated with decreased survival were treatment at a community cancer program,
Medicaid or Medicare insurance, Black race, increasing age, mastectomy,
moderately and poorly differentiated tumor grade, increasing T and N stage, and
higher Charlson Index Group. CONCLUSION: The survival benefit of expedited time
to initial surgical treatment varies by stage and appears to have the greatest
impact in early-stage disease. Prior to establishing standard metrics, further
quantification of the impact on patient outcomes is needed.
PMID- 27503493
TI - Exploiting Molecular and Immune Biology of Gastric and Gastroesophageal
Adenocarcinomas to Discover Novel Therapeutic Targets.
AB - Gastroesophageal carcinomas (GACs) are a significant problem worldwide, and
despite many attempts to improve the outcomes of patients with these tumors,
little progress has been made over the last several decades. In the past decade,
only transtuzumab and ramucirumab, two drugs with marginal clinical benefit, have
been approved for the treatment of patients with GACs. After second-line therapy,
most treatment options are generally ineffective. Prior studies in this disease
have been largely empiric, using unselected patient populations. More recently,
detailed somatic genotyping, enrichment of patients based on biomarkers, and
pharmacokinetic studies have opened new avenues for developing treatment options
in patients with GAC.
PMID- 27503494
TI - Racial Differences in Utilization of Breast Conservation Surgery: Results from
the National Cancer Data Base (NCDB).
AB - BACKGROUND: Whether rates of breast-conservation surgery (BCS) vary based on race
and ethnicity has not been clearly elucidated on a national leve. METHODS: The
National Cancer Data Base (NCDB) was used to identify women who underwent surgery
for invasive breast cancer during 2010 and 2011. The effect of race and ethnicity
on BCS rates was determined, independent of patient demographics, tumor-related
variables, and geographic region. RESULTS: There were 299,827 patients with known
race and ethnicity who underwent definitive breast surgery. BCS rates by race
were as follows: 135,065/241,236 (56.0 %) for whites, 17,819/33,301 (53.5 %) for
blacks, 4,722/9,508 (49.7 %) for Asian/Pacific Islanders, and 7,919/15,782 (50.2
%) for Hispanics (p < 0.001). Mean tumor size differed among the racial groups:
2.07 cm in whites, 2.54 cm in blacks, 2.23 cm in Asians, and 2.48 cm in Hispanics
(p < 0.001). When stratified by tumor size, BCS was most common in blacks and
least common in Asians for all tumors >2 cm (p < 0.001). On multivariable
analysis adjusted for age, tumor size, nodal status, grade, molecular type,
geographic area, urban/rural residence, insurance status, and census-derived
median income and education for the patient's zip code, the odds ratio for BCS
for blacks compared to whites was 1.23 (95 % confidence interval [CI] 1.20-1.27,
p < 0.001), for Asians was 0.84 (95 % CI 0.80-0.88, p < 0.001), and for Hispanics
was 1.00 (95 % CI 0.96-1.05, p = 0.885). CONCLUSIONS: When adjusted for patient
demographics, tumor-related variables, and geographic area, BCS rates are higher
in blacks and lower in Asians compared to whites.
PMID- 27503495
TI - Blinded predictions of host-guest standard free energies of binding in the SAMPL5
challenge.
AB - In the context of the SAMPL5 blinded challenge standard free energies of binding
were predicted for a dataset of 22 small guest molecules and three different host
molecules octa-acids (OAH and OAMe) and a cucurbituril (CBC). Three sets of
predictions were submitted, each based on different variations of classical
molecular dynamics alchemical free energy calculation protocols based on the
double annihilation method. The first model (model A) yields a free energy of
binding based on computed free energy changes in solvated and host-guest complex
phases; the second (model B) adds long range dispersion corrections to the
previous result; the third (model C) uses an additional standard state correction
term to account for the use of distance restraints during the molecular dynamics
simulations. Model C performs the best in terms of mean unsigned error for all
guests (MUE [Formula: see text]-95 % confidence interval) for the whole data set
and in particular for the octa-acid systems (MUE [Formula: see text]). The
overall correlation with experimental data for all models is encouraging
([Formula: see text]). The correlation between experimental and computational
free energy of binding ranks as one of the highest with respect to other entries
in the challenge. Nonetheless the large MUE for the best performing model
highlights systematic errors, and submissions from other groups fared better with
respect to this metric.
PMID- 27503496
TI - [Participatory research : Meaning, concept, objectives and methods].
AB - Shaping one's own life and feeling equal in society is an essential aspect of
participation. Based on the UN Convention on the Rights of Persons with
Disabilities, the Social Security Code IX and the International Classification of
Functioning, Disability and Health (ICF), participation is relevant for the
German health system. The cross-sectional discipline of participation research
investigates conditions for self-determined and equal participation in society.
Research results can reinforce and promote the participation of humans with
disabilities. Participation research uses established quantitative and
qualitative approaches. Moreover, participatory research is a relevant approach
that demands involving persons with disabilities in decisions in the research
process. In the future, it will be important to concentrate findings and to
connect researchers. The participation research action alliance (Aktionsbundnis
Teilhabeforschung), which was established in 2015, aims to make funding
accessible as well as strengthen and profile participation research.
PMID- 27503497
TI - [Environmental factors and the promotion of participation. The Perspective of
medical rehabilitation].
AB - BACKGROUND: The International Classification of Functioning, Disability and
Health (ICF), as well as the main goal of enabling participation, are of
fundamental importance for medical rehabilitation. According to the logic of the
ICF and its underlying multidimensional model of functioning and disability, the
participation of a person can be influenced by modelling environmental factors.
OBJECTIVES: This article presents environmental factors as defined by the ICF in
the context of medical rehabilitation and aims to answer to what extent
environmental factors are already involved in medical rehabilitation and if there
are further environmental factors with the potential of being involved in
interventions for improvement of participation. MATERIALS AND METHODS: An
analysis of documents with relevance to medical rehabilitation was done. Text
passages that referred to environmental factors were linked to the environmental
factor codes of the ICF. RESULTS AND CONCLUSIONS: The ICF and its underlying
model of functioning and disability provide a conceptual framework both for
making the current usage of environmental factors apparent and for deriving and
developing new intervention approaches with the involvement of environmental
factors. The analysis of documents showed that environmental factor codes vary in
how well they are represented in these documents. There are environmental factor
codes that are barely or not at all represented, but do have potential to
contribute to the improvement of participation.
PMID- 27503498
TI - [Data on disability and participation in Germany : Requirements, analysis options
and results].
AB - As a basis for political decisions and to meet the statistical requirements of
the CRPD, reliable data and reporting on the situation of people with
disabilities are essential. Based on results of the preliminary study for a
German participation survey, this article firstly defines data requirements and
areas of participation. Secondly, data sources regarding participation and
disability in Germany that were identified in a literature search are described
in detail. Only sources providing population-based data that are collected on a
regular basis and that could contribute to participation reporting were taken
into account. This includes data from official statistics, (panel) studies or
surveys, administrative data and reporting systems. Finally, we exemplarily
present the main statistical findings of the 2012 European health and social
integration survey (EHSIS), a survey that was specifically designed to
investigate participation of persons with disabilities. In addition to the
surveys identified in the preliminary study for a German participation survey
that could be used or expanded for participation reporting, and the data sources
used in the participation report published by the federal government in 2013, the
research yielded further publicly available data sources with a high potential
for a participation reporting system.
PMID- 27503499
TI - [Incapacitated persons - participation rights and the legal concept of the
capacity to consent].
AB - Legal problems related to the capacity to consent and decision-making have
recently become increasingly important. This concerns the prerequisites and
limitations of legal participation as a basis of social participation. Among the
relevant social spheres and fields of action, this particulary concerns medicine
and health care as well as disability and care. At the normative level, with a
view to those concerned, this leads to fundamental questions resulting from the
tension between self-determination and care as basic legal and ethical standards.
At the empirical level, there are debates between the law and the sciences with
regard to the relevant knowledge base for the assessment of (in)capacity to
consent. The traditional controversies about the relevant legal criteria
determining the existence or absence of capacity to consent are intensified by
some recent legal developments, two of which must be highlighted. One of these is
the postulate, increasingly emphasized by courts and legislator, of an at least
communicative involvement of persons incapable to give consent in the decision
making process. The other is the fundamental discussion of medical ethics on
concepts of assisted self-determination and supported decision-making, the
consequences of which will also be of relevance at the legal level. Insofar, the
development of guardianship law and the legal requirements of the UN Disability
Rights Convention are of particular importance.
PMID- 27503500
TI - [Antibiotic intake and resistance development - Knowledge, experience and
behavior among the German general population].
AB - BACKGROUND: The network project RAI (Rational Use of Antibiotics via Information
and Communication) is aimed at developing tailored information and communication
tools on the subject of antibiotic (AB) resistance for various stakeholder
groups. During the preparation phase, a survey was performed addressing the
German general population. OBJECTIVES: To gain insights into the knowledge,
attitudes, and behavior of nonprescribers concerning AB and multidrug-resistant
organisms (MDRO). METHODS: Using computer-assisted, telephone-based interviews a
random sample of 1,004 persons aged 14 years and older was surveyed. Descriptive
reporting of data and multivariate analysis were performed, including
sociodemographic variables. RESULTS: Only 24 % of participants knew that bacteria
(but not viruses or humans) could develop AB resistance. However, this knowledge
did not influence the outcome of other questions. Regardless of knowledge, 71 %
thought that the subject was important, but 58 % did not believe in the influence
of their own behavior on MDRO development. When visiting a physician, patients
were given an antibiotic three times as often as information on AB resistance. 17
% did not take the AB as prescribed and 20 % of all participants stated that they
personally knew at least one person with MDRO problems. This personal involvement
had a significant effect on the rating of self-influence, on the importance of
the subject, on the interaction between patient and physician (more information,
less AB), and on AB intake compliance (less frequent). DISCUSSION: We found
considerable knowledge gaps, but this had no impact on the assessment of the
subject. A starting point for an intervention could be patient-physician
communication. This seems more effective and safer than a public campaign.
PMID- 27503501
TI - Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with
CLL on single-agent ibrutinib.
AB - Ibrutinib is not known to confer risk for Pneumocystis jirovecii pneumonia (PCP).
We observed 5 cases of PCP in 96 patients receiving single-agent ibrutinib,
including 4 previously untreated. Clinical presentations included asymptomatic
pulmonary infiltrates, chronic cough, and shortness of breath. The diagnosis was
often delayed. Median time from starting ibrutinib to occurrence of PCP was 6
months (range, 2-24). The estimated incidence of PCP was 2.05 cases per 100
patient-years (95% confidence interval, 0.67-4.79). At the time of PCP, all
patients had CD4 T-cell count >500/MUL (median, 966/MUL) and immunoglobulin G
(IgG) >500 mg/dL (median, 727 mg/dL). All patients underwent bronchoalveolar
lavage. P jirovecii was identified by polymerase chain reaction in all 5 cases;
direct fluorescence antibody staining was positive in 1. All events were grade
<=2 and resolved with oral therapy. Secondary prophylaxis was not given to 3
patients; after 61 patient-months of follow up, no recurrence occurred. Lack of
correlation with CD4 count and IgG level suggests that susceptibility to PCP may
be linked to Bruton tyrosine kinase (BTK) inhibition. If confirmed, this
association could result in significant changes in surveillance and/or
prophylaxis, possibly extending to other BTK inhibitors. This trial was
registered at www.clinicaltrials.gov as #NCT01500733 and #NCT02514083.
PMID- 27503502
TI - Importance of environmental stiffness for megakaryocyte differentiation and
proplatelet formation.
AB - Megakaryocyte (MK) differentiation occurs within the bone marrow (BM), a complex
3-dimensional (3D) environment of low stiffness exerting local external
constraints. To evaluate the influence of the 3D mechanical constraints that MKs
may encounter in vivo, we differentiated mouse BM progenitors in methylcellulose
(MC) hydrogels tuned to mimic BM stiffness. We found that MKs grown in a medium
of 30- to 60-Pa stiffness more closely resembled those in the BM in terms of
demarcation membrane system (DMS) morphological aspect and exhibited higher
ploidy levels, as compared with MKs in liquid culture. Following resuspension in
a liquid medium, MC-grown MKs displayed twice as much proplatelet formation as
cells grown in liquid culture. Thus, the MC gel, by mimicking external
constraints, appeared to positively influence MK differentiation. To determine
whether MKs adapt to extracellular stiffness through mechanotransduction
involving actomyosin-based modulation of the intracellular tension, myosin
deficient (Myh9-/-) progenitors were grown in MC gels. Absence of myosin resulted
in abnormal cell deformation and strongly decreased proplatelet formation,
similarly to features observed for Myh9-/- MKs differentiated in situ but not in
vitro. Moreover, megakaryoblastic leukemia 1 (MKL1), a well-known actor in
mechanotransduction, was found to be preferentially relocated within the nucleus
of MC-differentiated MKs, whereas its inhibition prevented MC-mediated increased
proplatelet formation. Altogether, these data show that a 3D medium mimicking BM
stiffness contributes, through the myosin IIA and MKL1 pathways, to a more
favorable in vitro environment for MK differentiation, which ultimately
translates into increased proplatelet production.
PMID- 27503503
TI - Nocardiajiangsuensis sp. nov., an actinomycete isolated from coastal soil.
AB - A novel actinomycete strain, designated strain KLBMP S0027T, was isolated from a
coastal soil collected from the coastal region of Lianyungang, Jiangsu Province,
in east China, and was studied in detail for its taxonomic position. Comparative
16S rRNA gene sequence analysis showed that this strain belonged to the genus
Nocardia and was most closely related to Nocardia harenae WS-26T (98.5 %),
Nocardiaasiatica NBRC 100129T (98.5 %), Nocardiaabscessus NBRC 100374T (98.2 %),
Nocardia brasiliensis NBRC 14402T (98.2 %) and Nocardiacyriacigeorgica NBRC
100375T (98 %), respectively. The strain showed a combination of chemotaxonomic
and morphological properties typical of the genus Nocardia. The cell wall
contained meso-diaminopimelic acid (type IV), and whole-cell sugars were
arabinose, galactose, glucose and ribose. Strain KLBMP S0027T contained MK
8(H4omega-cycl) as the predominant menaquinone; C16 : 0, C18 : 1omega9c, C18 : 0
10-methyl (TBSA) and summed feature 3 (C16 : 1omega7c/C16 : 1omega6c) were the
major cellular fatty acids. The polar lipids detected were
diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, one
unknown glycolipid and two unknown lipids. Mycolic acids were detected. The G+C
content of the DNA was 70.5 %. However, a combination of DNA-DNA hybridization
and phenotypic data demonstrated that strain KLBMP S0027T could be clearly
distinguished from the type strain of the most closely related species, N.
harenae WS-26T. On the basis of the data presented from a polyphasic study, it
was evident that this strain should be assigned to a novel species of the genus
Nocardia, for which the name Nocardia jiangsuensis sp. nov. is proposed. The type
strain is KLBMP S0027T (=CGMCC 4.7330T=KCTC 39691T).
PMID- 27503505
TI - Update on ultrasound in bowel obstruction.
PMID- 27503504
TI - Combination of Paclitaxel and MG1 oncolytic virus as a successful strategy for
breast cancer treatment.
AB - BACKGROUND: Breast cancer is the most common malignant disease amongst Western
women. The lack of treatment options for patients with chemotherapy-resistant or
recurrent cancers is pushing the field toward the rapid development of novel
therapies. The use of oncolytic viruses is a promising approach for the treatment
of disseminated diseases like breast cancer, with the first candidate recently
approved by the Food and Drug Administration for use in patients. In this report,
we demonstrate the compatibility of oncolytic virotherapy and chemotherapy using
various murine breast cancer models. This one-two punch has been explored in the
past by several groups with different viruses and drugs and was shown to be a
successful approach. Our strategy is to combine Paclitaxel, one of the most
common drugs used to treat patients with breast cancer, and the oncolytic
Rhabdovirus Maraba-MG1, a clinical trial candidate in a study currently
recruiting patients with late-stage metastatic cancer. METHODS: We used the EMT6,
4 T1 and E0771 murine breast cancer models to evaluate in vitro and in vivo the
effects of co-treatment with MG1 and Paclitaxel. Treatment-induced cytotoxicity
was assessed and plaque assays, flow cytometry, microscopy and
immunocytochemistry analysis were performed to quantify virus production and
transgene expression. Orthotopically implanted tumors were measured during and
after treatment to evaluate efficacy and Kaplan-Meier survival curves were
generated. RESULTS: Our data demonstrate not only the compatibility of the
treatments, but also their synergistic cytopathic activity. With Paclitaxel, EMT6
and 4 T1 tumors demonstrated increased virus production both in vitro and in
vivo. Our results also show that Paclitaxel does not impair the safety profile of
the virus treatment. Importantly, when combined, MG1 and the drug controlled
tumor growth and prolonged survival. CONCLUSIONS: The combination of MG1 and
Paclitaxel improved efficacy in all of the breast cancer models we tested and
thus is a promising alternative approach for the treatment of patients with
refractory breast cancer. Our strategy has potential for rapid translation to the
clinic, given the current clinical status of both agents.
PMID- 27503507
TI - Customary law, traditional punishment, and death in the Anangu Pitjantjatjara
Yankunytjatjara (APY) lands of Central Australia.
PMID- 27503506
TI - Natal habitat imprinting counteracts the diversifying effects of phenotype
dependent dispersal in a spatially structured population.
AB - BACKGROUND: Habitat selection may have profound evolutionary consequences, but
they strongly depend on the underlying preference mechanism, including
genetically-determined, natal habitat and phenotype-dependent preferences. It is
known that different mechanisms may operate at the same time, yet their relative
contribution to population differentiation remains largely unexplored empirically
mainly because of the difficulty of finding suitable study systems. Here, we
investigate the role of early experience and genetic background in determining
the outcome of settlement by pied flycatchers (Ficedula hypoleuca) breeding in
two habitat patches between which dispersal and subsequent reproductive
performance is influenced by phenotype (body size). For this, we conducted a
cross-fostering experiment in a two-patch system: an oakwood and a conifer
plantation separated by only 1 km. RESULTS: Experimental birds mostly returned to
breed in the forest patch where they were raised, whether it was that of their
genetic or their foster parents, indicating that decisions on where to settle are
determined by individuals' experience in their natal site, rather than by their
genetic background. Nevertheless, nearly a third (27.6 %) moved away from the
rearing habitat and, as previously observed in unmanipulated individuals,
dispersal between habitats was phenotype-dependent. Pied flycatchers breeding in
the oak and the pine forests are differentiated by body size, and analyses of
genetic variation at microsatellite loci now provide evidence of subtle genetic
differentiation between the two populations. This suggests that phenotype
dependent dispersal may contribute to population structure despite the short
distance and widespread exchange of birds between the study plots. CONCLUSIONS:
Taken together, the current and previous findings that pied flycatchers do not
always settle in the habitat to which they are best suited suggest that their
strong tendency to return to the natal patch regardless of their body size might
lead to maladaptive settlement decisions and thus constrain the potential of
phenotype-dependent dispersal to promote microgeographic adaptation.
PMID- 27503508
TI - Unintentional asphyxia, SIDS, and medically explained deaths: a descriptive study
of outcomes of child death review (CDR) investigations following sudden
unexpected death in infancy.
AB - BACKGROUND: A comprehensive child death review (CDR) program was introduced in
England and Wales in 2008, but as yet data have only been analyzed at a local
level, limiting the learning from deaths. The aim of this study is to describe
the profile of causes and risk factors for sudden unexpected death in infancy
(SUDI) as determined by the new CDR program. METHODS: This was a descriptive
outcome study using data from child death overview panel Form C for SUDI cases
dying during 2010-2012 in the West Midlands region of England. The main outcome
measures were: cause of death, risk factors and potential preventability of
death, and determination of deaths probably due to unintentional asphyxia.
RESULTS: Data were obtained for 65/70 (93 %) SUDI cases. 20/65 (31 %) deaths were
initially categorized as due to medical causes; 21/65 (32 %) as SIDS; and 24/65
(37 %) as undetermined. Reanalysis suggested that 2/21 SIDS and 7/24 undetermined
deaths were probably due to unintentional asphyxia, with 6 of these involving co
sleeping and excessive parental alcohol consumption. Deaths classified as
"undetermined" had significantly higher total family and environmental risk
factor scores (mean 2.6, 95 % CI 2.0-3.3) compared to those classified as SIDS
(mean 1.6, 95 % CI 1.2-1.9), or medical causes for death (mean 1.1, 95 % CI 0.8
1.3). 9/20 (47 %) of medical deaths, 19/21 (90 %) SIDS, and 23/24 (96 %)
undetermined deaths were considered to be potentially preventable. There were
inadequacies in medical provision identified in 5/20 (25 %) of medically
explained deaths. CONCLUSIONS: The CDR program results in detailed information
about risk factors for SUDI cases but failed to recognize deaths probably due to
unintentional asphyxia. The misclassification of probable unintentional asphyxial
deaths and SIDS as "undetermined deaths" is likely to limit learning from these
deaths and inhibit prevention strategies. Many SUDI occurred in families with
mental illness, substance misuse and chaotic lifestyles and most in unsafe sleep
environments. This knowledge could be used to better target safe sleep advice for
vulnerable families and prevent SUDI in the future.
PMID- 27503509
TI - Stabbing energy and force required for pocket-knives to pierce ribs.
AB - PURPOSE: In addition to reconstructing the course of events, the medical examiner
will often have to answer questions regarding the force necessary to inflict a
certain injury in stabbing incidents. Several groups have examined the force
needed to penetrate soft-tissue and clothing; however, no studies addressing the
energy needed for penetrating ribs exist. Therefore, we decided to investigate
this force on an animal model. METHOD: Ribs from healthy, 8 to 10-month-old pigs
were used as a substitute for human ribs. These ribs were then stabbed either
transversely or longitudinally with two different pocket-knife blades, namely a
Swiss Army pocket knife and a sturdier pocket knife (Classic Schnitzmesser,
Herbertz Solingen) dropped from a drop-tower at defined heights and therefore
defined energies. RESULTS: Longitudinally orientated stabs showed complete
piercing of the ribs at approximately 11 Joules (J) or with a stabbing force in
excess of 906 Newton (N) for both blade types. Transversely orientated stabs,
however, displayed complete piercing between 11 and 16 J, or in excess of 1198 N,
with the sturdy pocket knife tending to require a little more energy than the
Swiss army pocket knife. CONCLUSIONS: Young adult porcine ribs are completely
pierced by pocket knife blades at energies between 11 and 16 J. Assuming the
porcine ribs are comparable to those ribs of young adult humans, our results
indicate that a complete penetration of the chest wall through the ribs by
stabbing with a pocket knife is rather easily achieved.
PMID- 27503510
TI - Palliative care for patients with heart failure: facilitators and barriers - a
cross sectional survey of German health care professionals.
AB - BACKGROUND: Compared to patients with cancer, heart failure patients are seldom
candidates for palliative care. Numerous studies have investigated reasons why
heart failure patients do not receive palliative care; however, none of these
studies have ever evaluated the situation in the German health care setting. This
study aims to identify German healthcare providers' (HCP) perception of barriers
and facilitators to palliative care of patients with chronic heart failure.
METHODS: We conducted an online-survey with 315 nurses and physicians of
different medical disciplines. RESULTS: Even though heart failure patients' need
of palliative care and its advantages has been recognized, HCP see potential for
development and improvement. A lack of knowledge about the content and measures
of palliative care, poor communication and unclear responsibilities between
medical disciplines, difficulties to determine the right time to initiate
palliative care, and the feeling not to be prepared to discuss end-of-life issues
with the patient has been identified as barriers. Further, HCP believe that
patients and relatives do not possess adequate knowledge about the disease and
its progression and are therefore unprepared in asking questions regarding
palliative care. They rather tend to demand everything possible to be done in
order prolong life, and are reluctant to accept that life is limited. Overall,
HCP perceive that dying is a taboo subject within our society placing palliative
care on the same level as assisted dying. In addition, results indicate that HCP
have an inappropriate notion of ideal medicine fearing to lose patient and are
worried about the appropriateness of PC remuneration. CONCLUSIONS: In order to
overcome the described barriers, HCP, patients, and relatives need to be educated
in palliative care. Information and education encompassing the aim, content and
measures of palliative care needs to be provided for all parties in order to
optimize patient care, to foster communication between healthcare professionals,
patients, and relatives, and to overcome perceived barriers. TRIAL REGISTRATION:
DRKS00007119.
PMID- 27503511
TI - Supersuppression: Reservoir Competency and Timing of Mosquito Host Shifts Combine
to Reduce Spillover of West Nile Virus.
AB - In the eastern United States, human cases of West Nile virus (WNV) result from
spillover from urban epizootic transmission between passerine birds and Culex
mosquitoes. In Atlanta, GA, substantial WNV presence in hosts and vectors has not
resulted in the human disease burden observed in cities with similar infection
pressure. Our study goal was to investigate extrinsic ecological conditions that
potentially contribute to these reduced transmission rates. We conducted WNV
surveillance among hosts and vectors in urban Atlanta and recorded an overall
avian seroprevalence of nearly 30%, which was significantly higher among northern
cardinals, blue jays, and members of the mimid family, and notably low among
American robins. Examination of temporal Culex feeding patterns showed a marked
feeding shift from American robins in the early season to northern cardinals in
the late season. We therefore rule out American robins as superspreaders in the
Atlanta area and suggest instead that northern cardinals and mimids act as WNV
"supersuppressor" species, which slow WNV transmission by drawing many infectious
bites during the critical virus amplification period, yet failing to amplify
transmission due to low host competencies. Of particular interest, urban forest
patches provide spillover protection by increasing the WNV amplification fraction
on supersuppressor species.
PMID- 27503512
TI - Plasma Tryptophan and the Kynurenine-Tryptophan Ratio are Associated with the
Acquisition of Statural Growth Deficits and Oral Vaccine Underperformance in
Populations with Environmental Enteropathy.
AB - Early childhood enteric infections have adverse impacts on child growth and can
inhibit normal mucosal responses to oral vaccines, two critical components of
environmental enteropathy. To evaluate the role of indoleamine 2,3-dioxygenase 1
(IDO1) activity and its relationship with these outcomes, we measured tryptophan
and the kynurenine-tryptophan ratio (KTR) in two longitudinal birth cohorts with
a high prevalence of stunting. Children in rural Peru and Tanzania (N = 494)
contributed 1,251 plasma samples at 3, 7, 15, and 24 months of age and monthly
anthropometrics from 0 to 36 months of age. Tryptophan concentrations were
directly associated with linear growth from 1 to 8 months after biomarker
assessment. A 1-SD increase in tryptophan concentration was associated with a
gain in length-for-age Z-score (LAZ) of 0.17 over the next 6 months in Peru (95%
confidence interval [CI] = 0.11-0.23, P < 0.001) and a gain in LAZ of 0.13 Z
scores in Tanzania (95% CI = 0.03-0.22, P = 0.009). Vaccine responsiveness data
were available for Peru only. An increase in kynurenine by 1 MUM was associated
with a 1.63 (95% CI = 1.13-2.34) increase in the odds of failure to poliovirus
type 1, but there was no association with tetanus vaccine response. A KTR of 52
was 76% sensitive and 50% specific in predicting failure of response to serotype
1 of the oral polio vaccine. KTR was associated with systemic markers of
inflammation, but also interleukin-10, supporting the association between IDO1
activity and immunotolerance. These results strongly suggest that the activity of
IDO1 is implicated in the pathophysiology of environmental enteropathy, and
demonstrates the utility of tryptophan and kynurenine as biomarkers for this
syndrome, particularly in identifying those at risk for hyporesponsivity to oral
vaccines.
PMID- 27503513
TI - Schistosoma mansoni in Gabon: Emerging or Ignored?
AB - Schistosomiasis affects millions of people across Africa. We detected eggs of
Schistosoma mansoni in western lowland gorilla and central chimpanzee fecal
samples in Loango National Park, Gabon. We analyzed nuclear and mitochondrial
DNA, namely internal transcribed spacer and cytochrome c oxidase subunit 1
fragments, and the resulting maximum likelihood phylogenetic analyses and
haplotype network of the ITS and COI, respectively, showed that the samples from
gorillas and chimpanzees clustered clearly within the S. mansoni clade. This is
the first confirmed record of S. mansoni from Gabon, which urges surveillance in
the area and prompts questions regarding the extent of zoonotic transmission and
the clinical impact.
PMID- 27503514
TI - Identification of a second HOXA2 nonsense mutation in a family with autosomal
dominant non-syndromic microtia and distinctive ear morphology.
AB - Microtia is a congenital defect affecting external ears, which appear smaller and
sometimes malformed. Here we describe a five-generation family with isolated
bilateral microtia segregating as an autosomal dominant trait. Similar features
have been previously observed in an autosomal dominant family with non-syndromic
microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2
biallelic mutations were also described in an inbreed family with autosomal
recessive microtia, hearing impairment and incomplete cleft palate. In our
family, sequence analysis detected a heterozygous protein truncating nonsense
variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and
absent in public databases. This study confirms the role of HOXA2 gene in
dominant isolated microtia and contribute to further define the dysmorphogenetic
effect of this gene on ear development.
PMID- 27503515
TI - Targeted delivery of vitamin D3-loaded nanoparticles to C6 glioma cell line
increased resistance to doxorubicin, epirubicin, and docetaxel in vitro.
AB - In recent years, targeted delivery systems have been used along with
combinatorial therapy to decrease drug resistance and increase cancer therapy
efficacy. The anti-proliferative effects of vitamin D3 (VD3) on cancerous cells,
such as C6 glioma, with active hedgehog pathways raised the question as to
whether pre-targeting C6 glioma cells with VD3-loaded nanoparticles (VD3NPs) can
enhance the anti-tumor effects of doxorubicin, epirobicin, and docetaxel on this
drug-resistant cell line. Here, studying at cellular, nuclear, protein, and gene
levels we demonstrated that VD3NP-doxorubicin and VD3NP-epirobicin combinations
increased the probability of chemotherapy/radiotherapy resistance and cancer stem
cell (CSC) properties in C6 glioma significantly (P < 0.05), compared to
doxorubicin and epirobicin alone. However, VD3NP-docetaxel combination may have
the potential in sensitizing C6 cells to ionizing irradiation, but this
combination also increased the CSC properties and the probability of drug
resistance significantly (P < 0.05), compared to docetaxel alone. Although our
previous study showed that targeted delivery of VD3 reduced the rate of
proliferation significantly (P < 0.05) in C6 glioma cells (a drug-resistant cell
line), here we concluded that combinatorial therapy of exogenous VD3 with
doxorubicin, epirobicin, and docetaxel not only did not lead to the enhancement
of cytotoxic effects of the aforementioned drugs but also increased the cancerous
characteristics in C6 glioma, in vitro.
PMID- 27503532
TI - Effusive-constrictive pericarditis, hepatitis, and pancreatitis in a patient with
possible coxsackievirus B infection: a case report.
AB - BACKGROUND: Coxsackie B is a viral pathogen that presents with various invasive
diseases in adults. Historically, the majority of adult cases with pericarditis
or myocarditis have been attributed to coxsackievirus B. The presentation of this
viral infection causing effusive-constrictive pericarditis, hepatitis or
pancreatitis is rare. This case report is the first to describe a patient with
concomitant effusive-constrictive pericarditis, hepatitis and pancreatitis from
possible coxsackievirus B infection. CASE PRESENTATION: A 26-year old female was
admitted to our hospital with the diagnosis of effusive-constrictive pericarditis
complicated by tamponade and cardiac arrest. An emergent pericardiocentesis was
performed successfully. Hepatitis and pancreatitis were also identified in our
patient. After an extensive workup, coxsackievirus B infection was suspected by
positive serum complement fixation antibody titers. Our patient made a full
recovery and was discharged from the hospital. CONCLUSION: Clinical suspicion of
effusive-constrictive pericarditis with tamponade from coxsackievirus B should be
considered in patients presenting with chest pain, dyspnea, jugular venous
distention, hypotension, ST segment elevation on electrocardiogram, and
ventricular interdependence with septal shift during diastole on transthoracic
echocardiogram. Initial diagnoses of effusive-constrictive pericarditis
resembling cardiac tamponade, hepatitis and pancreatitis can be challenging, and
this case highlights the need for healthcare professionals to be cognizant of the
association between these unusual clinical presentations and coxsackievirus B
infection.
PMID- 27503516
TI - Amniotic membrane mesenchymal stem cells can differentiate into germ cells in
vitro.
AB - This is the first report on differentiation of mouse amniotic membrane
mesenchymal stem cells (AM-MSCs) into male germ cells (GCs). AM-MSCs have the
multipotent differentiation capacity and can be differentiated into various cell
types. In the present study, AM-MSCs were induced for differentiation into GCs.
AM-MSCs were isolated from mouse embryonic membrane by enzymatic digestion. AM
MSCs were characterized with osteogenic and adipogenic differentiation test and
flow cytometric analysis of some CD-markers. AM-MSCs were induced to
differentiate into GCs using a creative two-step method. Passage-3 AM-MSCs were
firstly treated with 25 ng/ml bone morphogenetic protein 4 (BMP4) for 5 d and in
continuing with 1 MUM retinoic acid (RA) for 12 d (total treatment time was 17
d). At the end of the treatment period, real-time reverse transcription (RT)-PCR
was performed to evaluate the expression of GC-specific markers-Itgb1, Dazl,
Stra8, Piwil2, Mvh, Oct4, and c-Kit- in the cells. Moreover, flow cytometry and
immunofluorescence staining were performed to evaluate the expression of Mvh and
Dazl at protein level. Real-time RT-PCR showed that most of the tested markers
were upregulated in the treated AM-MSCs. Furthermore, flow cytometric and
immunofluorescence analyses both revealed that a considerable part of the treated
cells expressed GC-specific markers. The percentage of positive cells for Mvh and
Dazl was about 23 and 46%, respectively. Our results indicated that a number of
AM-MSCs successfully differentiated into the GCs. Finally, it seems that AM-MSCs
would be a potential source of adult pluripotent stem cells for in vitro
generation of GCs and cell-based therapies for treatment of infertility.
PMID- 27503533
TI - Three-dimensional corrective osteotomies of complex malunited humeral fractures
using patient-specific guides.
AB - BACKGROUND: Corrective osteotomies of malunited fractures of the proximal and
distal humerus are among the most demanding orthopedic procedures. Whereas the
restoration of the normal humeral anatomy is the ultimate goal, the
quantification of the deformity as well as the transfer of the preoperative plan
is challenging. The purpose of this study was to provide a guideline for 3
dimensional (3D) corrective osteotomies of malunited intra-articular fractures of
the humerus and a detailed overview of existing and novel instruments to enlarge
the toolkit for 3D preoperative planning and intraoperative realization using
patient-specific guides. METHODS: We describe the preoperative 3D deformity
analysis, relevant considerations for the preoperative plan, design of the
patient-specific guides, and surgical technique of corrective osteotomies of the
humerus. RESULTS: The presented technique demonstrates the benefit of computer
assisted surgery for complex osteotomies of the humerus from a preoperative
deformity analysis to the creation of feasible surgical procedures and the
generation of patient-specific guides. CONCLUSIONS: A 3D analysis of a post
traumatic deformity of the humerus, 3D preoperative planning, and use of patient
specific guides facilitate corrective osteotomies of complex malunited humeral
fractures.
PMID- 27503534
TI - In Situ and Timed Extraction of Cellular Peptides from Live HeLa Cells by Photo
Switchable Mesoporous Silica Nanocarriers.
AB - In situ and timed extraction of cellular peptides is a great challenge for
dynamic and global proteomic investigation of live cells. In this work, a
mesoporous silica nanocarrier with photoswitchable off/on coumarin gates (MSNcg)
was developed for capturing peptides from the cytosol of living HeLa cells. The
MSNcg was constructed from mesoporous silica nanoparticle (MSN) and its
subsequent modifications with TAT peptides and coumarin, to endow the features of
the size-exclusion effect of the mesoporous silica and the localization of
nanocarrier at cytosol by TAT peptide and to control the closing and opening of
the coumarin gates by reversible photodimerization and photocleavage. With the
pre-endocytosing of MSNcg, 126 cytosol peptides were harvested and identified
from living HeLa cells. Moreover, 3 peptides were captured containing dynamic and
changeable information. The extraction strategy of using MSNcg exhibited
promising potentials in the in situ and dynamic extraction of endogenous peptides
and/or proteins from living systems.
PMID- 27503535
TI - Identification of urinary tract pathogens after 3-hours urine culture by MALDI
TOF mass spectrometry.
AB - Complicated urinary tract infections, such as pyelonephritis, may lead to sepsis.
Rapid diagnosis is needed to identify the causative urinary pathogen and to
verify the appropriate empirical antimicrobial therapy. We describe here a rapid
identification method for urinary pathogens: urine is incubated on chocolate agar
for 3h at 35 degrees C with 5% CO2 and subjected to MALDI-TOF MS analysis by
VITEK MS. Overall 207 screened clinical urine samples were tested in parallel
with conventional urine culture. The method, called U-si-MALDI-TOF (urine short
incubation MALDI-TOF), showed correct identification for 86% of Gram-negative
urinary tract pathogens (Escherichia coli, Klebsiella pneumoniae, and other
Enterobacteriaceae), when present at >10(5)cfu/ml in culture (n=107), compared
with conventional culture method. However, Gram-positive bacteria (n=28) were not
successfully identified by U-si-MALDI-TOF. This method is especially suitable for
rapid identification of E. coli, the most common cause of urinary tract
infections and urosepsis. Turnaround time for identification using U-si-MALDI-TOF
compared with conventional urine culture was improved from 24h to 4-6h.
PMID- 27503536
TI - Label-free analysis of mononuclear human blood cells in microfluidic flow by
coherent imaging tools.
AB - The investigation of the physical properties of peripheral blood mononuclear
cells (PBMC) is of great relevance, as they play a key role in regulating human
body health. Here we report the possibility to characterize human PBMC in their
physiological conditions in a microfluidic-based measurement system. A
viscoelastic polymer solution is adopted for 3D alignment of individual cells
inflow. An optical signature (OS) acquisition of each flowing cell is performed
using a wide angle light scattering apparatus. Besides, a quantitative phase
imaging (QPI) holographic system is employed with the aim (i) to check the
position in flow of individual cells using a holographic 3D cell tracking method;
and (ii) to estimate their 3D morphometric features, such as their refractive
index (RI). Results obtained by combining OS and QPI have been compared with
literature values, showing good agreement. The results confirm the possibility to
obtain sub-micrometric details of physical cell properties in microfluidic flow,
avoiding chemical staining or fluorescent labelling.
PMID- 27503537
TI - A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end
resection.
AB - There are two major and alternative pathways to repair DNA double-strand breaks:
non-homologous end-joining and homologous recombination. Here we identify and
characterize novel factors involved in choosing between these pathways; in this
study we took advantage of the SeeSaw Reporter, in which the repair of double
strand breaks by homology-independent or -dependent mechanisms is distinguished
by the accumulation of green or red fluorescence, respectively. Using a genome
wide human esiRNA (endoribonuclease-prepared siRNA) library, we isolate genes
that control the recombination/end-joining ratio. Here we report that two
distinct sets of genes are involved in the control of the balance between NHEJ
and HR: those that are required to facilitate recombination and those that favour
NHEJ. This last category includes CCAR2/DBC1, which we show inhibits
recombination by limiting the initiation and the extent of DNA end resection,
thereby acting as an antagonist of CtIP.
PMID- 27503538
TI - Fat removal using a new cryolipolysis device: a retrospective study of 418
procedures.
PMID- 27503539
TI - Fine mapping and identification of candidate genes for a QTL affecting
Meloidogyne incognita reproduction in Upland cotton.
AB - BACKGROUND: The southern root-knot nematode (Meloidogyne incognita; RKN) is one
of the most important economic pests of Upland cotton (Gossypium hirsutum L.).
Host plant resistance, the ability of a plant to suppress nematode reproduction,
is the most economical, practical, and environmentally sound method to provide
protection against this subterranean pest. The resistant line Auburn 623RNR and a
number of elite breeding lines derived from it remain the most important source
of root-knot nematode (RKN) resistance. Prior genetic analysis has identified two
epistatically interacting RKN resistance QTLs, qMi-C11 and qMi-C14, affecting
gall formation and RKN reproduction, respectively. RESULTS: We developed a
genetic population segregating only for the qMi-C14 locus and evaluated the
genetic effects of this QTL on RKN resistance in the absence of the qMi-C11
locus. The qMi-C14 locus had a LOD score of 12 and accounted for 24.5 % of total
phenotypic variation for egg production. In addition to not being significantly
associated with gall formation, this locus had a lower main effect on RKN
reproduction than found in our previous study, which lends further support to
evidence of epistasis with qMi-C11 in imparting RKN resistance in the Auburn
623RNR source. The locus qMi-C14 was fine-mapped with the addition of 16 newly
developed markers. By using the reference genome sequence of G. raimondii, we
identified 20 candidate genes encoding disease resistance protein homologs in the
newly defined 2.3 Mb region flanked by two SSR markers. Resequencing of an RKN
resistant and susceptible G. hirsutum germplasm revealed non-synonymous mutations
in only four of the coding regions of candidate genes, and these four genes are
consequently of high interest. CONCLUSIONS: Our mapping results validated the
effects of the qMi-C14 resistance locus, delimiting the QTL to a smaller region,
and identified tightly linked SSR markers to improve the efficiency of marker
assisted selection. The candidate genes identified warrant functional studies
that will help in identifying and characterizing the actual qMi-C14 defense
gene(s) against root-knot nematodes.
PMID- 27503540
TI - Contemporary sex differences among patients with acute coronary syndrome treated
by emergency percutaneous coronary intervention.
AB - Acute coronary syndrome (ACS) is an important cause of mortality and morbidity in
the general population. Recent advances in percutaneous coronary intervention
(PCI) and optimal medical treatment have helped to improve the prognosis of
patients with ACS. The previous reports indicated that women with ACS have a
higher risk of adverse outcomes. However, sex differences in clinical outcomes
with contemporary coronary revascularization and medical therapy for ACS have not
been elucidated. We analyzed data from 676 consecutive patients with ACS (female,
n = 166; male, n = 510) who were treated by emergency PCI between 2011 and 2014
at Juntendo Shizuoka Hospital. The patients were grouped according to sex. We
defined major adverse cardiovascular events as a composite of all-cause death and
ACS recurrence at 1 year and compared rates of major adverse cardiac events
(MACE) between the groups. Women were older (75.4 +/- 11.0 vs. 66.2 +/- 12.2
years) and had a higher rate of multi-vessel disease, chronic kidney disease, and
Killip IV at presentation. The cumulative rate of MACE at 1 year was
significantly higher among women than men (17.5 vs. 10.2 %, p = 0.02, log-rank
test). However, the association between women and a higher risk of MACE was
attenuated after adjusting for age (HR 1.25, 95 % CI 0.77-2.00, p = 0.36) and
other variables (HR 0.93, 95 % CI 0.36-2.44, p = 0.88). Adjustment for age and
other risk factors attenuated sex differences in mid-term clinical outcomes among
patients with ACS after emergency PCI.
PMID- 27503541
TI - Erratum to: Characterization of iodinated disinfection by-products in chlorinated
and chloraminated waters using Orbitrap based gas chromatography-mass
spectrometry.
PMID- 27503542
TI - An isotope dilution capillary electrophoresis/tandem mass spectrometry (CE-MS/MS)
method for the simultaneous measurement of choline, betaine, and dimethylglycine
concentrations in human plasma.
AB - Plasma concentrations of choline, betaine, and dimethylglycine provide valuable
information on the flow of methyl groups in key biological processes,
particularly during folate deficiency states. We developed a new method to
simultaneously measure these analytes in human plasma. Following sample
deproteinization using acetonitrile, an aliquot was evaporated to dryness under
vacuum to be then taken up by water. Finally, analytes were separated by
capillary electrophoresis and detected by electrospray ionization triple
quadrupole mass spectrometry, in multiple reaction monitoring mode, using two
stable isotope-labeled internal standards. Linearity of the calibration curves of
each analyte was good (R(2) > 0.99). Average limits of detection (LODs) and
limits of quantification (LOQs) for choline, betaine, and dimethylglycine were,
respectively, 0.43, 0.62, and 0.31 MUmol/L and 1.52, 2.11, and 0.97 MUmol/L. Mean
recovery of three replicates of two spiked concentrations levels was close to 100
% for all of the analytes. Repeatability and intermediate precision, expressed as
%RSD of measurements, were <9 %. The method, applied to measure analytes in
samples from 30 patients with chronic kidney disease and 30 age- and sex-matched
healthy controls, was able to detect differences between groups and the sexes.
PMID- 27503543
TI - Development and application of ultrasound-assisted microextraction to analysis of
fenitrothion in environmental samples.
AB - A microextraction technique based on ultrasonic emulsification and
demulsification was developed for detecting pesticides at trace levels in
environmental water samples. In this ultrasound-assisted microextraction (UAME),
chloroform was emulsified with an aqueous sample solution containing trace
fenitrothion (MEP) by ultrasonic irradiation (48 kHz) for 5 min. The emulsion was
then demulsified by ultrasonic irradiation (2.4 MHz) for 10 min. This resulted in
phase separation of the water and chloroform without centrifugation. The
demulsified chloroform was collected by a microsyringe and submitted to gas
chromatography-mass spectrometry. In conventional extraction with mechanical
stirring, the extraction recovery (ER) of MEP was strongly dependent on the
sample/chloroform volume ratio. However, in UAME, the ER was independent of the
volume ratio and the ER was >80 % when the enrichment factor was 40. In UAME, MEP
was rapidly extracted into the chloroform because of the large specific surface
areas of the small chloroform droplets in the oil-in-water (O/W) emulsion. This
gave a high extraction efficiency for MEP. UAME is a simple method requiring only
a change in the ultrasound frequency and with no pretreatment steps that could
contaminate the sample. The suitability of UAME was demonstrated by application
to the detection of trace levels of pesticides in a spiked water sample from a
fish tank. Graphical abstract Schematic diagram of the ultrasound-assisted
microextraction (UAME) method.
PMID- 27503544
TI - Practical utilization of spICP-MS to study sucrose density gradient
centrifugation for the separation of nanoparticles.
AB - Single particle inductively coupled plasma mass spectrometry (spICP-MS) is shown
to be a practical technique to study the efficacy of rate-zonal sucrose density
gradient centrifugation (SDGC) separations of mixtures of gold nanoparticles
(AuNPs) in liquid suspension. spICP-MS enabled measurements of AuNP size
distributions and particle number concentrations along the gradient, allowing
unambiguous evaluations of the effectiveness of the separation. Importantly,
these studies were conducted using AuNP concentrations that are directly relevant
to environmental studies (sub ng mL-1). At such low concentrations, other
techniques [e.g., dynamic light scattering (DLS), transmission and scanning
electron microscopies (TEM and SEM), UV-vis spectroscopy, atomic force microscopy
(AFM)] do not have adequate sensitivity, highlighting the inherent value of spICP
MS for this and similar applications. In terms of the SDGC separations, a mixture
containing three populations of AuNPs, having mean diameters of 30, 80, and 150
nm, was fully separated, while separations of two other mixtures (30, 60, 100 nm;
and 20, 50, 100 nm) were less successful. Finally, it is shown that the
separation capacity of SDGC can be overwhelmed when particle number
concentrations are excessive, an especially relevant finding in view of common
methodologies taken in nanotechnology research. Graphical Abstract
Characterization of the separation of a gold nanoparticle mixture by sucrose
density gradient centrifugation by conventional and single particle ICP-MS
analysis.
PMID- 27503545
TI - Application of microwave-assisted extraction and ultra-high performance liquid
chromatography-tandem mass spectrometry for the analysis of sex hormones and
corticosteroids in sewage sludge samples.
AB - Hormonal compounds are a concern to the international community because they can
affect the aquatic biota and are therefore considered to be endocrine-disrupting
compounds. These compounds have lipophilic properties, so they tend to accumulate
in solid matrices, such as sewage sludge. This work presents the optimization of
a microwave-assisted extraction process combined with ultra-high performance
liquid chromatography-tandem mass spectrometry for the determination of 15
hormonal compounds in sludge samples. The proposed method has relative standard
deviations below 23 %, good recoveries (over 71 %) for all compounds, detection
limits that ranged from 1.1 to 7.9 ng g(-1) and quantification limits which
ranged from 3.7 to 26.3 ng g(-1). The method was used to analyse sludge samples
from four different wastewater treatment plants of Gran Canaria (Spain) with
different wastewater treatments. 17beta-estradiol, 17alpha-ethynylestradiol,
norgestrel and cortisone were detected in sludge samples at concentrations that
ranged from 17.3 to 1.44 * 10(3) ng g(-1). The developed method permits the use
of small quantities of sample and organic solvents, presents short extractions
times and is the first one based on microwave-assisted extraction for the
analysis of both sex hormones and corticosteroids.
PMID- 27503546
TI - Silk-Fibroin and Graphene Oxide Composites Promote Human Periodontal Ligament
Stem Cell Spontaneous Differentiation into Osteo/Cementoblast-Like Cells.
AB - Graphene represents one of the most interesting additions to the tissue
engineering toolbox. Novel graphene-based composites are required to improve the
beneficial graphene properties in terms of tridimensional polymeric structure,
conferring a higher mechanical strength and favoring the differentiation of human
mesenchymal stem cells. Here, we have demonstrated in a wide range of composite
combinations, the successful use of graphene and silk-fibroin constructs for
future bioengineering applications in the field of clinical regenerative
dentistry using human periodontal ligament stem cells. Our results provide
exciting new data for the development of suitable scaffolds that allow good cell
engrafting, preservation of cell viability and proliferation, promotion of
spontaneous osteoblastic differentiation, and importantly, stimulation of a
higher cementum physiological synthesis than using other different available
biomaterials.
PMID- 27503547
TI - Erratum: Graphic analysis of flow-volume curves: a pilot study.
PMID- 27503548
TI - Contra-lateral hip fracture in the elderly: are decreased body mass index and
skin thickness predictive factors?
AB - PURPOSE: A correlation between soft tissue thickness and osteoporosis has been
suggested. We aimed to estimate if a low body mass index (BMI) and/or a decrease
of skin thickness could estimate the risk of contra-lateral hip fracture.
METHODS: First, we performed a retrospective analysis of 1268 patients treated
for a hip fracture. The 146 patients who had a contra-lateral hip fractures-study
group-were compared with the 1078 patients who did not-control group. Four BMI
categories were considered: obese, overweight, normal weight and low weight.
Second, we enrolled prospectively 1000 consecutive patients in the emergency
department. History of fractures, BMI, and skin aspect on the dorsum of both
hands-classified as severe decrease thickness, moderate decrease thickness or
normal-were recorded. RESULTS: pt?>In the first part, we found that patients with
contra-lateral fractures had a significantly lower BMI than those in the control
group (22.2 Vs 26.5 kg/m2, p = 0.01). In the second part, 48 on 1000 patients had
a hip fracture. Among them, six had a contra-lateral fracture. BMI was 23.4 kg/m2
in bilateral hip fractures, 33.68 kg/m2 in the unilateral fracture group, and
28.04 kg/m2 in the non-fracture group (p = 0.04). Finally, patients with contra
lateral hip fractures had a severe decrease thickness of the skin. CONCLUSION: A
low BMI and a decreased skin thickness increase independently the risk of
fractures by three times. When associated, they increase the risk of fracture
risk by five times. This combination had a sensitivity at 71 % and a specificity
at 90 % for predicting hip fracture.
PMID- 27503549
TI - Rotavirus vaccines contribute towards universal health coverage in a mixed public
private healthcare system.
AB - OBJECTIVES: To evaluate rotavirus vaccination in Malaysia from the household's
perspective. The extended cost-effectiveness analysis (ECEA) framework quantifies
the broader value of universal vaccination starting with non-health benefits such
as financial risk protection and equity. These dimensions better enable decision
makers to evaluate policy on the public finance of health programmes. METHODS:
The incidence, health service utilisation and household expenditure related to
rotavirus gastroenteritis according to national income quintiles were obtained
from local data sources. Multiple birth cohorts were distributed into income
quintiles and followed from birth over the first five years of life in a
multicohort, static model. RESULTS: We found that the rich pay more out of pocket
(OOP) than the poor, as the rich use more expensive private care. OOP payments
among the poorest although small are high as a proportion of household income.
Rotavirus vaccination results in substantial reduction in rotavirus episodes and
expenditure and provides financial risk protection to all income groups. Poverty
reduction benefits are concentrated amongst the poorest two income quintiles.
CONCLUSION: We propose that universal vaccination complements health financing
reforms in strengthening Universal Health Coverage (UHC). ECEA provides an
important tool to understand the implications of vaccination for UHC, beyond
traditional considerations of economic efficiency.
PMID- 27503550
TI - Coronary bifurcation stent morphology in dual-source CT: validation with micro
CT.
AB - The aim of this study is to analyze post-bifurcation coronary stent morphology in
vitro using dual-source CT and validate those findings using micro-CT. Nine
silicon coronary artery phantoms simulating main branch (MB) and side branch (SB)
were prepared using a 3-D printer. After bifurcation stenting using Crush,
Culotte, and T-stenting technique, in vitro CT imaging was conducted using both
dual-source CT and micro-CT. Morphological change of the bifurcation stent
including crushed segment and floating stent strut were evaluated. Dual-source CT
was able to demonstrate morphologic changes of bifurcation stents and was
comparable to micro-CT. In stents with Crush and T-stenting methods, crushed
segment appeared denser and thicker than other stent parts and was located at MB
side in all phantoms. Floating strut was observed in half of the phantoms with
Crush technique and all phantoms with T-stenting. Parameters measured in both
dual-source CT and micro-CT showed good correlation and high agreement (limits of
agreement and correlation for length, perimeter and area, 0.3 +/- 3.5, 0.5 +/-
2.1 mm, and 0.0 +/- 1.5 mm2, r = 0.76, 0.92, and 0.91). The morphology of post
bifurcation stent on dual-source CT correlates well with that of micro-CT in the
coronary artery phantom. Coronary CT angiography may be a feasible method for the
evaluation of stent morphology in patients who underwent bifurcation stenting.
PMID- 27503552
TI - An atomic symmetry-controlled thermal switch.
AB - We propose a simple diatomic system trapped inside an optical cavity to control
the energy flow between two thermal baths. Through the action of the baths the
system is driven to a non-equilibrium steady state. Using the Large Deviation
theory we show that the number of photons flowing between the two baths is
dramatically different depending on the symmetry of the atomic states. Here we
present a deterministic scheme to prepare symmetric and antisymmetric atomic
states with the use of external driving fields, thus implementing an atomic
control switch for the energy flow.
PMID- 27503551
TI - Early gadolinium enhancement in hypertrophic cardiomyopathy: a potential
premature marker of myocardial damage.
AB - Early gadolinium enhancement (EGE), one CMR diagnostic criteria in acute
myocarditis, has been related with hyperemia and capillary leakage. The value of
EGE in hypertrophic cardiomyopathy (HCM) remains unknown. Our aim was to
determine the prevalence of EGE in patients with HCM, and its relation with late
gadolinium enhancement (LGE). The association of EGE with morphological and
clinical parameters was also evaluated. Sixty consecutive patients with HCM and
CMR from our center were included. All the clinical and complementary test
information was collected prospectively in our HCM clinic. Left ventricular (LV)
measurements were calculated from cine sequences. EGE and LGE were quantified
with a dedicated software. Clinical events were collected from medical records. A
slow wash-out pattern on EGE was detected in up to 68 % of the patients, being an
isolated finding without LGE in 10 (16 %). This cohort showed a greater maximal
LV wall thickness (20.1 +/- 4 vs. 18.1 +/- 3.5 mm, p = 0.010) and asymmetry ratio
(1.86 +/- 0.42 vs. 1.62 +/- 0.46; p = 0.039). The percentage of EGE/slice and the
difference with the percentage LGE/slice demonstrated a significant positive
correlation with the maximal LV wall thickness (Rho 0.450 and 0.386
respectively). EGE also correlated with number of segments with LVH (LV
hypertrophy) and the asymmetry ratio. Neither EGE nor LGE were associated with
classical risk factors, the risk score for sudden cardiac death, or with major
clinical events. EGE was a frequent finding in HCM, even in absence of LGE. This
phenomenon showed a positive correlation with morphological markers of disease
burden.
PMID- 27503553
TI - Heterologous production of an acidic thermostable lipase with broad-range pH
activity from thermophilic fungus Neosartorya fischeri P1.
AB - Thermophilic Neosartorya fischeri P1 is an excellent lipase producer and harbors
seven lipase genes. All genes were found to be functional after heterologous
expression in Escherichia coli. One of them, LIP09, showed high-level expression
in Pichia pastoris with the yield of 2.0 g/L in a 3.7-L fermentor. Deduced amino
acid sequence of LIP09 consists of a putative signal peptide (residues 1-19) and
a mature polypeptide (residues 20-562). Compared with other fungal counterparts,
purified recombinant LIP09 has some superior properties. It exhibited maximum
activity at 60 degrees C and pH 5.0, had broad pH adaptability (>60% activity at
pH 3.5-8.0) and stability (retaining >90% activity after incubation at pH 3.0-7.0
for 1 h at 40 degrees C), and was highly thermostable (retaining >96% activity
after incubation at 50 degrees C for 30 min). The r-LIP09 had a preference for
the medium-chain length p-nitrophenyl esters (C12) rather than short and long
chain length substrates. The high-level expression and excellent properties make
LIP09 a potential enzyme candidate in food and feed industries.
PMID- 27503555
TI - Rapid and large-scale synthesis of bare Co3O4 porous nanostructures from an
oleate precursor as superior Li-ion anodes with long-cycle lives.
AB - In this study, we describe a rapid and environmentally friendly synthesis of bare
Co3O4 nanocrystals derived from Co(ii) oleate complexes by calcination treatment.
When directly used as anode materials for lithium-ion batteries (LIBs), the as
prepared nanocrystals could deliver a high reversible capacity of 980 mA h g(-1)
after 250 cycles at a current density of 100 mA g(-1) and excellent cycling
performance, which may be beneficial to promote the further development of the
next generation of lithium ion batteries. The synthetic route can offer great
advantages for the flash preparation of other metal oxide nanocrystals for energy
storage application.
PMID- 27503554
TI - Estimating safe maximum levels of vitamins and minerals in fortified foods and
food supplements.
AB - PURPOSE: To show how safe maximum levels (SML) of vitamins and minerals in
fortified foods and supplements may be estimated in population subgroups.
METHODS: SML were estimated for adults and 7- to 10-year-old children for six
nutrients (retinol, vitamins B6, D and E, folic acid, iron and calcium) using
data on usual daily nutrient intakes from Irish national nutrition surveys.
RESULTS: SML of nutrients in supplements were lower for children than for adults,
except for calcium and iron. Daily energy intake from fortified foods in high
consumers (95th percentile) varied by nutrient from 138 to 342 kcal in adults and
40-309 kcal in children. SML (/100 kcal) of nutrients in fortified food were
lower for children than adults for vitamins B6 and D, higher for vitamin E, with
little difference for other nutrients. Including 25 % 'overage' for nutrients in
fortified foods and supplements had little effect on SML. Nutritionally
significant amounts of these nutrients can be added safely to supplements and
fortified foods for these population subgroups. The estimated SML of nutrients in
fortified foods and supplements may be considered safe for these population
subgroups over the long term given the food composition and dietary patterns
prevailing in the respective dietary surveys. CONCLUSIONS: This risk assessment
approach shows how nutrient intake data may be used to estimate, for population
subgroups, the SML for vitamins and minerals in both fortified foods and
supplements, separately, each taking into account the intake from other dietary
sources.
PMID- 27503557
TI - An Interview with Rick Neubig.
PMID- 27503556
TI - Tristetraprolin as a Therapeutic Target in Inflammatory Disease.
AB - Members of the tristetraprolin (TTP) family of RNA-binding proteins are found in
all major eukaryotic groups. TTP family members, from plants through humans, can
bind adenosine-uridine rich elements in target mRNAs with high affinity. In
mammalian cells, these proteins then promote deadenylation and decay of target
transcripts. Four such proteins are found in mice, of which the best studied is
TTP. When the gene encoding TTP is disrupted in mice, the animals develop a
severe syndrome of arthritis, autoimmunity, cachexia, dermatitis, and myeloid
hyperplasia. Conversely, recent overexpression studies have demonstrated
protection against several experimental models of immune inflammatory disease.
This endogenous anti-inflammatory protein could serve as the basis for novel
approaches to therapy of similar conditions in humans.
PMID- 27503558
TI - N w-hydroxy-L-arginine as a novel ethnic specific indicator of estrogen-negative
breast cancer.
AB - As a heterogeneous disease, breast cancer can be divided into distinct subtypes.
Among the two major subsets of estrogen receptor-negative (ER-) and ER-positive
(ER+) tumors, the ER- is a more aggressive subtype, more difficult to treat, has
greater ethnic disparity concerns, worse prognosis, and almost twice the risk of
mortality. We provide here a fundamental delineation of N w-hydroxy-L-arginine as
a sensitive and reliable ethnic specific indicator for ER- breast cancer early
prognosis (United States provisional patent application number 62232816).
PMID- 27503559
TI - Transglutaminase 2-specific coeliac disease autoantibodies induce morphological
changes and signs of inflammation in the small-bowel mucosa of mice.
AB - Coeliac disease is hallmarked by an abnormal immune reaction against ingested
wheat-, rye- and barley-derived gluten and the presence of transglutaminase 2
(TG2)-targeted autoantibodies. The small-bowel mucosal damage characteristic of
the disorder develops gradually from normal villus morphology to inflammation and
finally to villus atrophy with crypt hyperplasia. Patients with early-stage
coeliac disease have TG2-autoantibodies present in serum and small-intestinal
mucosa and they may already suffer from abdominal symptoms before the development
of villus atrophy. Previously, we have shown that intraperitoneal injections of
coeliac patient-derived sera or purified immunoglobulin fraction into mice induce
a condition mimicking early-stage coeliac disease. In the current study, we
sought to establish whether recombinantly produced patient-derived TG2-targeted
autoantibodies are by themselves sufficient for the development of such an
experimentally induced condition in immune-compromised mice. Interestingly, mice
injected with coeliac patient TG2-antibodies had altered small-intestinal mucosal
morphology, increased lamina propria cellular infiltration and disease-specific
autoantibodies deposited in the small bowel, but did not evince clinical features
of the disease. Thus, coeliac patient-derived TG2-specific autoantibodies seem to
be sufficient for the induction of subtle small-bowel mucosal alterations in
mice, but the development of clinical features probably requires additional
factors such as other antibody populations relevant in coeliac disease.
PMID- 27503560
TI - 11,000 years of craniofacial and mandibular variation in Lower Nubia.
AB - The transition to agriculture was a key event in human history. The extent to
which this transition is associated with biological changes in different world
regions remains debated. Cultural and osteological records in Lower Nubia
throughout the Holocene have been interpreted as a result of in situ
differentiation or alternatively as migratory events and possible admixture with
surrounding populations. Here we investigated the patterns of craniofacial and
mandibular variation from Mesolithic hunting-gathering to late farming, a period
spanning 11,000 years. We analyzed 102 adult specimens spanning five cultural
horizons: Mesolithic, A-group, C-group, Pharaonic and Meroitic, by means of 3D
geometric morphometric methods, in order to assess shape variation and diachronic
patterns at the transition to farming and in subsequent periods. Our results
highlight a strong morphometric distinction between Mesolithic hunter-gatherers
and farmers as well as differences between transitional and intensive farmers in
mandibular variation which is consistent with differential impact of selective
pressures on different regions of the skull. This study corroborates a major
biological change during the transition from hunting to farming, supporting the
masticatory-functional hypothesis for the mandible and suggesting population
continuity among farming populations throughout the Holocene based on the overall
shape of the cranium.
PMID- 27503561
TI - Deciphering the role of the AT-rich interaction domain and the HMG-box domain of
ARID-HMG proteins of Arabidopsis thaliana.
AB - ARID-HMG DNA-binding proteins represent a novel group of HMG-box containing
protein family where the AT-rich interaction domain (ARID) is fused with the HMG
box domain in a single polypeptide chain. ARID-HMG proteins are highly plant
specific with homologs found both in flowering plants as well as in moss such as
Physcomitrella. The expression of these proteins is ubiquitous in plant tissues
and primarily localises in the cell nucleus. HMGB proteins are involved in
several nuclear processes, but the role of ARID-HMG proteins in plants remains
poorly explored. Here, we performed DNA-protein interaction studies with
Arabidopsis ARID-HMG protein HMGB11 (At1g55650) to understand the functionality
of this protein and its individual domains. DNA binding assays revealed that
AtHMGB11 can bind double-stranded DNA with a weaker affinity (Kd = 475 +/- 17.9
nM) compared to Arabidopsis HMGB1 protein (Kd = 39.8 +/- 2.68 nM). AtHMGB11 also
prefers AT-rich DNA as a substrate and shows structural bias for supercoiled DNA.
Molecular docking of the DNA-AtHMGB11 complex indicated that the protein
interacts with the DNA major groove, mainly through its ARID domain and the
junction region connecting the ARID and the HMG-box domain. Also, predicted by
the docking model, mutation of Lys(85) from the ARID domain and Arg(199) &
Lys(202) from the junction region affects the DNA binding affinity of AtHMGB11.
In addition, AtHMGB11 and its truncated form containing the HMG-box domain can
not only promote DNA mini-circle formation but are also capable of inducing
negative supercoils into relaxed plasmid DNA suggesting the involvement of this
protein in several nuclear events. Overall, the study signifies that both the
ARID and the HMG-box domain contribute to the optimal functioning of ARID-HMG
protein in vivo.
PMID- 27503562
TI - Soliton driven angiogenesis.
AB - Angiogenesis is a multiscale process by which blood vessels grow from existing
ones and carry oxygen to distant organs. Angiogenesis is essential for normal
organ growth and wounded tissue repair but it may also be induced by tumours to
amplify their own growth. Mathematical and computational models contribute to
understanding angiogenesis and developing anti-angiogenic drugs, but most work
only involves numerical simulations and analysis has lagged. A recent stochastic
model of tumour-induced angiogenesis including blood vessel branching,
elongation, and anastomosis captures some of its intrinsic multiscale structures,
yet allows one to extract a deterministic integropartial differential description
of the vessel tip density. Here we find that the latter advances chemotactically
towards the tumour driven by a soliton (similar to the famous Korteweg-de Vries
soliton) whose shape and velocity change slowly. Analysing these collective
coordinates paves the way for controlling angiogenesis through the soliton, the
engine that drives this process.
PMID- 25492891
TI - Transrectal ultrasonography of anorectal diseases: advantages and disadvantages.
AB - Transrectal ultrasonography (TRUS) has been widely accepted as a popular imaging
modality for evaluating the lower rectum, anal sphincters, and pelvic floor in
patients with various anorectal diseases. It provides excellent visualization of
the layers of the rectal wall and of the anatomy of the anal canal. TRUS is an
accurate tool for the staging of primary rectal cancer, especially for early
stages. Although magnetic resonance imaging is a modality complementary to TRUS
with advantages for evaluating the mesorectum, external sphincter, and deep
pelvic inflammation, three-dimensional ultrasonography improves the detection and
characterization of perianal fistulas and therefore plays a crucial role in
optimal treatment planning. The operator should be familiar with the anatomy of
the rectum and pelvic structures relevant to the preoperative evaluation of
rectal cancer and other anal canal diseases, and should have technical
proficiency in the use of TRUS combined with an awareness of its limitations
compared to magnetic resonance imaging.
PMID- 27503564
TI - Publication of Cost-of-Illness Studies: Does Methodological Complexity Matter?
PMID- 27503565
TI - The Six-Food Elimination Diet for Eosinophilic Esophagitis Increases Grocery
Shopping Cost and Complexity.
AB - The six-food elimination diet (SFED), where dairy, wheat, eggs, soy, nuts, and
seafood are avoided, is an effective treatment for eosinophilic esophagitis
(EoE). Patient-related costs of this approach, however, are unknown. We aimed to
assess the cost of and ease of shopping for an SFED compared to an unrestricted
diet. A dietitian with expertise in EoE generated menus meeting dietary
requirements for a week's worth of meals for the SFED and an unrestricted diet.
We compared prices and the number of missing items for both diets at standard and
specialty grocery stores. The average weekly price of the SFED at a standard
supermarket was $92.54 compared to $79.84 for an unrestricted diet (p = 0.0001).
A patient shopping at a standard grocery store needed a higher proportion of
items from a second store compared to an unrestricted diet (32 vs. 3 %, p =
0.0001). The prices of the SFED and unrestricted diet using a specialty
supermarket were comparable ($106.47 vs. $105.96, p = 0.81), as was the
percentage of items requiring a trip to a second store (6 vs. 2 % items, p =
0.03). Shopping at a specialty grocery store increased weekly grocery costs by
$13.93 (p = 0.04) for the SFED and $26.12 (p = 0.03) for the unrestricted diet.
In conclusion, for patients shopping at standard grocery stores, the cost of an
SFED is higher, and an SFED requires more items from a second store. These
differences disappear at specialty grocery stores, but costs were significantly
higher. This cost and logistical burden can inform patients when selecting
dietary therapy.
PMID- 27503566
TI - A Comparative Study Between Two Sensory Stimulation Strategies After Two Weeks
Treatment on Older Patients with Oropharyngeal Dysphagia.
AB - Oropharyngeal dysphagia (OD) is a prevalent geriatric syndrome. Treatment is
based on compensatory strategies to avoid complications. New treatments based on
sensory stimulation to promote the recovery of the swallowing function have
proved effective in acute studies but prolonged treatment needs further research.
Our aim was to evaluate and compare the effect of two, longer-term sensory
treatment strategies on older patients with OD. 38 older patients (>=70 years)
were studied with videofluoroscopy (pre/posttreatment) and randomized into two 10
day treatment groups: Group A-transient receptor potential vanilloid 1 (TRPV1)
agonist (capsaicin 1 * 10(-5) M) and Group B-transcutaneous sensory electrical
stimulation (TSES) (Intelect VitalStim, biphasic pulses, 300 MUs, 80 Hz).
Patients were analyzed for treatment response. Patients were old (80.47 +/- 5.2
years), with comorbidities (3.11 +/- 1.59 Charlson Index), polymedication (8.92
+/- 3.31 drugs/patient), and mild functional impairment (86.84 +/- 17.84 Barthel
Index), and 28.9 % were at risk of malnutrition (MNA-sf). Overall, all patients
had videofluoroscopic signs of impaired safety of swallow (ISS) with delayed
oropharyngeal swallow response (OSR). After sensory stimulation, prevalence of
ISS decreased to 68.42 % in both groups (P = 0.019). There were 68.42 %
responders in Group A (TRPV1) and 42.11 % in Group B (TSES). Group A responders
showed an improvement in the penetration-aspiration scale (PAS, 5.23 +/- 2.04 to
3 +/- 1.47; P = 0.002), and the same was true for those of Group B (4.63 +/- 1.41
to 2.13 +/- 0.64; P = 0.007). 10-day sensory stimulation with either therapy
improved safety of swallow and OSR in older patients with OD, reducing the
severity of OD in a significant subgroup of these patients.
PMID- 27503567
TI - Carotid stiffness is associated with impairment of cognitive performance in
individuals with and without type 2 diabetes. The Maastricht Study.
AB - BACKGROUND AND AIMS: There is increasing evidence linking arterial (mainly
aortic) stiffness and type 2 diabetes, a risk factor for arterial stiffness, to
cognitive impairment and dementia. However, data on carotid stiffness, which may
be especially relevant for cognitive performance, are scarce, and few studies
have addressed the interplay between arterial stiffness, type 2 diabetes, and
cognitive performance. METHODS: We studied individuals with (n = 197) and without
(n = 528) type 2 diabetes, who completed a neuropsychological test battery and
underwent applanation tonometry and vascular ultrasound to evaluate aortic (i.e.
carotid-to-femoral pulse wave velocity) and carotid stiffness (i.e.
distensibility, compliance and Young's elastic modulus). Linear regression
analyses were performed and adjusted for demographics, vascular risk factors, and
depression. RESULTS: Overall, our results showed that carotid, but not aortic,
stiffness was associated with worse cognitive performance, primarily in the
domains of processing speed (standardized regression coefficient for
distensibility -0.083, p = 0.040; compliance -0.077, p = 0.032) and executive
function and attention (distensibility -0.133, p = 0.001; compliance -0.090, p =
0.015; Young's elastic modulus -0.081, p = 0.027). These associations did not
differ by diabetes status. The differences in cognitive performance between
individuals with and without type 2 diabetes (mean difference in domain scores
relative to those without diabetes for free recall memory -0.23, processing speed
-0.19, executive function and attention -0.23; all p <= 0.009 and adjusted for
demographics, traditional vascular risk factors, and depression) were not
substantially altered after additional adjustment for carotid stiffness.
CONCLUSIONS: Our findings suggest that carotid stiffness is associated with
cognitive performance in both individuals with and without diabetes, but does not
mediate the relationship between type 2 diabetes and cognitive dysfunction.
PMID- 27503569
TI - Equal variations of the Fermi level and work function in graphene at the
nanoscale.
AB - If surface effects are neglected, any change of the Fermi level in a
semiconductor is expected to result in an equal and opposite change of the work
function. However, this is in general not observed in three-dimensional
semiconductors, because of Fermi level pinning at the surface. By combining
Kelvin probe force microscopy and scanning tunneling spectroscopy on single layer
graphene, we measure both the local work function and the charge carrier density.
The one-to-one equivalence of changes in the Fermi level and the work function is
demonstrated to accurately hold in single layer graphene down to the nanometer
scale.
PMID- 27503568
TI - Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous
esophageal cells.
AB - The histone deacetylase (HDAC) inhibitor vorinostat has received significant
attention in recent years as an 'epigenetic' drug used to treat solid tumors.
However, its mechanisms of action are not entirely understood, particularly with
regard to its interaction with the aberrations in 3D nuclear structure that
accompany neoplastic progression. We investigated the impact of vorinostat on
human esophageal epithelial cell lines derived from normal, metaplastic (pre
cancerous), and malignant tissue. Using a combination of novel optical computed
tomography (CT)-based quantitative 3D absorption microscopy and conventional
confocal fluorescence microscopy, we show that subjecting malignant cells to
vorinostat preferentially alters their 3D nuclear architecture relative to non
cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that
drug-treated cancer cells exhibit significant alterations in nuclear morphometry.
Confocal microscopy revealed that vorinostat caused changes in the distribution
of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin.
Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA
repair gene MGMT was accompanied by spatial relocation toward the center of the
nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data
suggest that vorinostat's differential modulation of 3D nuclear architecture in
normal and abnormal cells could play a functional role in its anti-cancer action.
PMID- 27503570
TI - Mechanism of action of pimavanserin in Parkinson's disease psychosis: targeting
serotonin 5HT2A and 5HT2C receptors.
AB - Pimavanserin, a novel agent approved for the treatment of Parkinson's disease
psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A
receptors and less potent antagonist/inverse agonist actions at 5HT2C receptors.
PMID- 27503571
TI - ICD and DSM: neuroplasticity and staging are still missing.
AB - The two main diagnostic systems, the International Classification of Diseases
(ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM), have
undergone a number of revisions since their first editions: whereas the fifth
edition of the DSM has been published in 2013, the eleventh revision of the ICD
is expected by 2018. Although the process of harmonization between the 2 systems
is still a debated topic, the forthcoming revision of the ICD is seemingly
converging toward the DSM approach in regard to the reclassification of a number
of disorders. Nevertheless, the 2 systems still exhibit considerable differences,
partly due to their different purposes, development and revision processes, and
target audiences. Furthermore, while alternative and innovative classification
approaches are emerging with the aim of integrating the latest findings from
neuroscience and genomics, both the DSM and ICD still fail to incorporate core
concepts such as the clinical staging of psychiatric disorders and
"neuroprogression," as well as an adequate consideration of endophenotypes.
PMID- 27503572
TI - The separation of adult separation anxiety disorder.
AB - The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
categorization of mental disorders places "separation anxiety disorder" within
the broad group of anxiety disorders, and its diagnosis no longer rests on
establishing an onset during childhood or adolescence. In previous editions of
DSM, it was included within the disorders usually first diagnosed in infancy,
childhood, or adolescence, with the requirement for an onset of symptoms before
the age of 18 years: symptomatic adults could only receive a retrospective
diagnosis, based on establishing this early onset. The new position of separation
anxiety disorder is based upon the findings of epidemiological studies that
revealed the unexpectedly high prevalence of the condition in adults, often in
individuals with an onset of symptoms after the teenage years; its prominent
place within the DSM-5 group of anxiety disorders should encourage further
research into its epidemiology, etiology, and treatment. This review examines the
clinical features and boundaries of the condition, and offers guidance on how it
can be distinguished from other anxiety disorders and other mental disorders in
which "separation anxiety" may be apparent.
PMID- 27503573
TI - Development of deep eutectic solvents applied in extraction and separation.
AB - Deep eutectic solvents, as an alternative to ionic liquids, have greener
credentials than ionic liquids, and have attracted considerable attention in
related chemical research. Deep eutectic solvents have attracted increasing
attention in chemistry for the extraction and separation of various target
compounds from natural products. This review highlights the preparation of deep
eutectic solvents, unique properties of deep eutectic solvents, and synthesis of
deep-eutectic-solvent-based materials. On the other hand, application in the
extraction and separation of deep eutectic solvents is also included in this
report. In this paper, the available data and references in this field are
reviewed to summarize the applications and developments of deep eutectic
solvents. Based on the development of deep eutectic solvents, an exploitation of
new deep eutectic solvents and deep eutectic solvents-based materials is expected
to diversify into extraction and separation.
PMID- 27503574
TI - Evolutionary theory of ageing and the problem of correlated Gompertz parameters.
AB - The Gompertz mortality model is often used to evaluate evolutionary theories of
ageing, such as the Medawar-Williams' hypothesis that high extrinsic mortality
leads to faster ageing. However, fits of the Gompertz mortality model to data
often find the opposite result that mortality is negatively correlated with the
rate of ageing. This negative correlation has been independently discovered in
several taxa and is known in actuarial studies of ageing as the Strehler-Mildvan
correlation. We examine the role of mortality selection in determining late-life
variation in susceptibility to death, which has been suggested to be the cause of
this negative correlation. We demonstrate that fixed-frailty models that account
for heterogeneity in frailty do not remove the correlation and that the
correlation is an inherent statistical property of the Gompertz distribution.
Linking actuarial and biological rates of ageing will continue to be a pressing
challenge, but the Strehler-Mildvan correlation itself should not be used to
diagnose any biological, physiological, or evolutionary process. These findings
resolve some key tensions between theory and data that affect evolutionary and
biological studies of ageing and mortality. Tests of evolutionary theories of
ageing should include direct measures of physiological performance or condition.
PMID- 27503575
TI - Perioperative Complications and Outcome of Laparoscopic Cholecystectomy in 20
Dogs.
AB - OBJECTIVE: To report the complications and outcome of dogs undergoing
laparoscopic cholecystectomy for uncomplicated gall bladder disease. STUDY
DESIGN: Multi-institutional case series. ANIMALS: Client-owned dogs (n=20).
METHODS: Medical records of dogs that underwent laparoscopic cholecystectomy were
reviewed and signalment, history, clinical and ultrasound examination findings,
surgical variables, and complications were collated. Laparoscopic cholecystectomy
was performed using a multiport approach. Data were compared between dogs with
successful laparoscopic cholecystectomy and dogs requiring conversion to open
cholecystectomy. RESULTS: Six dogs (30%) required conversion from laparoscopic to
open cholecystectomy due to inability to ligate the cystic duct (3), evidence of
gall bladder rupture (1), leakage from the cystic duct during dissection (1), and
cardiac arrest (1). Cystic duct dissection was performed in 19 dogs using an
articulating dissector (10), right angle forceps (7), and unrecorded (2). The
cystic duct was ligated in 15 dogs using surgical clips (5), suture (6), or a
combination (4). All dogs were discharged from the hospital and had resolution of
clinical signs, although 1 dog developed pancreatitis and 1 dog required revision
surgery for bile peritonitis. There was no significant difference in preoperative
blood analysis results, surgical technique, or duration of hospitalization
between dogs undergoing laparoscopic cholecystectomy and cases converted to open
cholecystectomy. CONCLUSION: Laparoscopic cholecystectomy can be performed
successfully for uncomplicated gall bladder disease in dogs after careful case
selection. The surgeon considering laparoscopic cholecystectomy should be
familiar with a variety of methods for cystic duct dissection and ligation to
avoid difficulties during the procedure.
PMID- 27503576
TI - Isolation and characterization of hepatitis C virus resistant to a novel
phenanthridinone derivative.
AB - BACKGROUND: The novel phenanthridinone derivative HA-719 has recently been
identified as a highly potent and selective inhibitor of hepatitis C virus
replication. To elucidate its mechanism of inhibition, we have isolated and
analyzed a clone of hepatitis C virus replicon cells resistant to HA-719.
METHODS: To isolate HA-719-resistant replicon cells, Huh-7 cells containing
subgenomic hepatitis C virus replicons (genotype 1b) with a luciferase reporter
(LucNeo#2) were cultured in the presence of G418 and escalating concentrations of
HA-719. After several passages, total RNA was extracted from the growing cells,
and Huh-7 cells were transfected with the extracted RNA. Limiting dilution of the
transfected cells was performed to obtain an HA-719-resistant clone. RESULTS: The
50% effective concentration (EC50) of HA-719 for hepatitis C virus replication
was 0.058 +/- 0.012 uM in LucNeo#2 cells. The replicon cells capable of growing
in the presence of G418 and 3 uM HA-719 were obtained after 18 passages (72
days). The HA-719-resistant clone LucNeo719R showed 98.3-fold resistant to the
compound (EC50 = 5.66 +/- 0.92 uM), but the clone had no cross-resistance to
telaprevir (NS3 inhibitor), daclatasvir (NS5A inhibitor), and VX-222 (NS5B
inhibitor). The sequence analysis for the wild-type and LucNeo719R identified 3,
2 and 7 mutations in NS3/4 A, NS4B, and NS5A, respectively, but no mutations in
NS5B. CONCLUSION: None of the amino acid mutations in the resistant clone
corresponds to those reported to confer drug-resistance to current anti-hepatitis
C virus agents, suggesting that the target of HA-719 for hepatitis C virus
inhibition differs from those of the existing agents.
PMID- 27503577
TI - Melatonin decreases brain apoptosis, oxidative stress, and CD200 expression and
increased survival rate in mice infected by Venezuelan equine encephalitis virus.
AB - BACKGROUND: Pro-inflammatory and oxidative events during brain Venezuelan equine
encephalitis virus infection could lead to apoptosis and induce anti-inflammatory
responses (increased expression of CD200). The aim of this study was to determine
the effect of melatonin on brain apoptosis, oxidative stress, and CD200 molecule
in mice and neuroblastoma cultures infected by Venezuelan equine encephalitis
virus. METHODS: Mice were infected with 10 median lethal doses (LD50) of
Venezuelan equine encephalitis virus, treated with melatonin (500 ug/kg bw; three
days before infection and during all experimental time) and sacrificed on days 1,
3, and 5 postinfection. Brain samples were obtained at those periods of time. In
addition, infected neuroblastoma cell cultures (multiplicity of infection [MOI]:
1) were treated with 0, 0.1, 0.5, and 1 mM of melatonin and analyzed at 2, 4, and
6 h. CD200 and apoptosis expressions were analyzed by immunohistochemistry and
TUNEL assay, respectively. Nitrites and malondialdehyde were determined by
appropriate biochemical methods. RESULTS: Increased brain expression of
apoptosis, nitrite, and malondialdehyde productions and CD200 of infected mice
were found. Melatonin diminished those expressions. Similarly, high apoptosis
expression and nitrite and malondialdehyde productions on infected neuroblastoma
cultures were diminished by melatonin. Melatonin increased the survival rate
(25%) in Venezuelan equine encephalitis virus-infected animals compared with
untreated infected mice (0%). CONCLUSIONS: Neurological damage during brain
Venezuelan equine encephalitis virus infection could be mediated by apoptosis and
oxidative stress and CD200 molecule could be an important anti-inflammatory
response. Melatonin could be beneficial reducing apoptosis and oxidative stress.
PMID- 27503578
TI - Population differences in S-warfarin pharmacokinetics among African Americans,
Asians and whites: their influence on pharmacogenetic dosing algorithms.
AB - Using population pharmacokinetic analysis (PPK), we attempted to identify
predictors of S-warfarin clearance (CL(S)) and to clarify population differences
in S-warfarin pharmacokinetics among a cohort of 378 African American, Asian and
white patients. Significant predictors of CL(S) included clinical (age, body
weight and sex) and genotypic (CYP2C9*2,*3 and *8) factors, as well as African
American ethnicity, the median CL(S) being 30% lower in the latter than in Asians
and whites (170 versus 243 and 250 ml h-1, P<0.01). The plasma S-warfarin (Cp(S))
time courses following the genotype-based dosing algorithms simulated using the
PPK estimates showed African Americans with CYP2C9*1/*1 and any of the VKORC1
genotypes would have an average Cp(S) at steady state 1.5-1.8 times higher than
in Asians and whites. These results indicate warfarin dosing algorithms should be
evaluated in each respective ethnic population. Further study of a large African
American cohort will be necessary to confirm the present findings.
PMID- 27503579
TI - Clinical relevance of EMT and stem-like gene expression in circulating tumor
cells of metastatic colorectal cancer patients.
AB - : Using approved methods, circulating tumor cells (CTCs) are only isolated from
blood in 30%-50% of metastatic colorectal cancer (mCRC) patients. We previously
validated a technique to isolate circulating tumor cells (CTCs) in a cohort of
mCRC patients by combining immunomagnetic enrichment of EpCAM+/CD45- cells with
qRT-PCR amplification of CK20 and survivin expression. Here, we examined the
prognostic utility of CTC epithelial-mesenchymal transition (EMT) and stem cell
gene expression. An 8 ml blood sample was collected from 78 consecutive mCRC
patients before treatment with investigational and standard chemotherapeutics.
The mRNA expression of EMT (PI3Kalpha, Akt-2, Twist1) and stem cell (ALDH1)
markers was measured. Associations between CTC gene expression and progression
free survival (PFS) and overall survival (OS) were determined using Cox
regression models. Among patients without CK20 or survivin-expressing CTCs
(n=17), 55% had expression of ALDH1, PI3Kalpha and/or Akt-2. Patients with
positive CTC Akt-2 expression had a significantly shorter median PFS (3.0 versus
4.0 months) compared with those without CTC Akt-2 expression in univariable
(hazard ratio (HR)=1.61; log-rank P=0.034) and multivariable analyses (HR=1.70;
adjusted P=0.041). In univariable analysis, CTC ALDH1 expression was associated
with shorter OS (10.0 versus 38.6 months; HR=2.04, P=0.021). Patients with CTCs
expressing ALDH1, PI3Kalpha and/or Akt-2 had a significantly inferior PFS (3.0
versus 7.7 months; HR=1.88, P=0.015) and OS (10.0 versus 26.8+ months; HR=2.25,
P=0.050) in univariable, but not multivariable, analysis. CONCLUSIONS: CTC Akt-2
expression may serve as a clinically useful prognostic marker in mCRC patients
and warrants further evaluation in prospective trials.
PMID- 27503580
TI - CXCR4 polymorphism predicts progression-free survival in metastatic colorectal
cancer patients treated with first-line bevacizumab-based chemotherapy.
AB - We analyzed associations between CXCR4/CXCL12 single-nucleotide polymorphisms and
outcomes in metastatic colorectal cancer (mCRC) patients who underwent first-line
bevacizumab-based chemotherapy. A total of 874 patients were included in this
study: 144 treated with bevacizumab and FOLFOX or XELOX (training cohort), 653
treated with bevacizumab and FOLFIRI or FOLFOXIRI (validation cohort A or B) and
77 treated with cetuximab- and oxaliplatin-based regimens (control cohort). One
CXCR4 polymorphism (rs2228014) and two CXCL12 polymorphisms (rs1801157 and
rs3740085) were analyzed by PCR-based direct sequencing. Patients with a C/C
genotype had a prolonged progression-free survival (PFS) compared with those with
any T allele (P=0.030) in the training cohort. Similarly, patients with the C/C
genotype had a superior PFS in the validation cohorts, but not in the control
cohort. Our findings suggest that a common genetic variant, CXCR4 rs2228014,
could predict PFS and may guide therapeutic decisions in mCRC patients receiving
first-line bevacizumab-based chemotherapy.
PMID- 27503581
TI - Irinotecan-induced toxicity pharmacogenetics: an umbrella review of systematic
reviews and meta-analyses.
AB - Irinotecan chemotherapy toxicities can be severe, and may result in treatment
delay, morbidity and in some rare cases death. This systematic review of
systematic reviews synthesises all meta-analyses on biomarkers for irinotecan
toxicity across all genetic models for Asians, Caucasians, low dose, medium/high
dose and regimens with and without fluorouracil. False-positive findings are a
problem in pharmacogenetics, increasing the importance of systematic reviews.
Four systematic reviews that investigated the effect of the polymorphisms
UGT1A1*6 and/or*28 on neutropenia or diarrhoea toxicity were included. Both
UGT1A1*6 and *28 were reliably demonstrated to be risk factors for irinotecan
induced neutropenia, with tests for both polymorphisms potentially being
particularly useful in Asian cancer patients. UGT1A1*6 and *28 were also related
to diarrhoea toxicity; however, at low doses of irinotecan there was evidence
that UGT1A1*28 was not. In synthesising the best available evidence, this
umbrella systematic review provides a novel reference for clinicians applying
personalised medicine and identifies important research gaps.
PMID- 27503582
TI - Posterior Urethral Suspension During Robot-Assisted Radical Prostatectomy
Improves Early Urinary Control: A Prospective Cohort Study.
AB - PURPOSE: Early urinary control is a major goal for patients undergoing robot
assisted radical prostatectomy (RARP). We report our technique of posterior
urethral suspension (PUS) performed at the time of urethrovesical anastomosis.
PATIENTS AND METHODS: We prospectively followed men with localized prostate
cancer undergoing RARP by a single surgeon from August 2012 to October 2015.
Patients before April 2014 underwent only bladder neck preservation (controls),
while patients after April 2014 also underwent PUS. Patients were given a
modified Expanded Prostate Cancer Index Composite questionnaire, along with
questions depicting objective measures of urinary control (type of pad, number of
pads, wetness of pad). Time points queried were preoperatively and
postoperatively at weeks 1, 2, 4, and 12. Our primary outcome was pad-free
survival. RESULTS: Questionnaire response rate was 52% (56/107) for controls and
43% (36/83) for PUS. There were no differences in baseline demographics,
preoperative urinary control, intraoperative variables, or postoperative
complications between groups. There were few subjective improvements in urinary
control for PUS compared with controls. More notable, PUS patients had
significantly improved objective measures of urinary control, including less
protective incontinence products at 1 and 2 weeks after catheter removal (p <
0.03). They also wore fewer pads and had less leakage on each pad that lasted
from week 1 to week 4 after catheter removal (p < 0.01). PUS patients had pad
free rates of 37%, 47%, 54%, and 60% compared with controls 15%, 18%, 24%, and
36%, at weeks 1, 2, 4, and 12 after catheter removal (p = 0.07). CONCLUSION: PUS
may improve objective measures of early urinary control compared with controls.
With no increase in operative time and no change in complication rates, further
work in a randomized setting would provide additional weight to our findings.
PMID- 27503583
TI - J(Si,H) Coupling Constants in Nonclassical Transition-Metal Silane Complexes.
AB - We will outline that the sign and magnitude of J(Si,H) coupling constants provide
a highly sensitive tool to measure the extent of Si-H bond activation in
nonclassical silane complexes. Up to now, this structure-property relationship
was obscured by erroneous J(Si,H) sign determinations in the literature. These
new findings also help to identify the salient control parameters of the Si-H
bond activation process in nonclassical silane complexes.
PMID- 27503585
TI - Conventional versus drug-eluting beads chemoembolization for hepatocellular
carcinoma: Emphasis on the impact of tumor size.
AB - BACKGROUND AND AIM: This study aims to evaluate clinical outcomes of patients
with hepatocellular carcinoma who underwent transarterial chemoembolization
(TACE) using drug-eluting beads (DEB). PATIENTS AND METHODS: This study
retrospectively compared the clinical outcomes of 250 consecutive patients who
underwent DEB-TACE (n = 106) or conventional TACE (cTACE) (n = 144) in a tertiary
center between January 2010 and April 2014. The median age of the patients was 62
years and 81.6% were men. The primary endpoint was overall survival (OS). The
time to progression (TTP), radiological response rate using modified response
evaluation criteria in solid tumors criteria at 1 month after treatment, and
complication rates within 1 month were also compared. RESULTS: The most common
etiology was hepatitis B virus infection. The median index tumor size was 2.8 cm,
and 150 (60.0%) patients had Barcelona Clinic Liver Cancer stage B. Median TTP in
the cTACE group was longer than in the DEB-TACE group (13.3 vs10.8 months; P =
0.023). However, DEB-TACE and cTACE groups showed no significant differences for
mean OS (46.6 vs 44.9 months; P = 0.660) and disease control rate at 1 month
(78.3% vs 86.8%; P = 0.076). The OS, TTP, and disease control rate were also not
different between two groups, even when subgrouped by index tumor size. The
complication rates within 1 month were higher in the cTACE group (6.6% vs 14.6%;
P = 0.048). CONCLUSIONS: Drug-eluting beads TACE appears to be a safe intra
arterial therapy. However, it is not superior to cTACE in terms of efficacy.
Tumor size might not be a criterion to select treatment modality between cTACE
and DEB-TACE in terms of efficacy.
PMID- 27503584
TI - Breast cancer cells alter the dynamics of stromal fibronectin-collagen
interactions.
AB - Breast cancer cells recruit surrounding stromal cells, such as cancer-associated
fibroblasts (CAFs), to remodel their extracellular matrix (ECM) and promote
invasive tumor growth. Two major ECM components, fibronectin (Fn) and collagen I
(Col I), are known to interact with each other to regulate cellular behavior. In
this study, we seek to understand how Fn and Col I interplay and promote a
dysregulated signaling pathway to facilitate tumor progression. Specifically, we
investigated the evolution of tumor-conditioned stromal ECM composition,
structure, and relaxation. Furthermore, we assessed how evolving Fn-Col I
interactions gradually affected pro-angiogenic signaling. Our data first indicate
that CAFs initially assembled a strained, viscous, and unfolded Fn matrix. This
early altered Fn matrix was later remodeled into a thick Col I-rich matrix that
was characteristic of a dense tumor mass. Next, our results suggest that this ECM
remodeling was primarily mediated by matrix metalloproteinases (MMPs). This MMP
activity caused profound structural and mechanical changes in the developing ECM,
which then modified vascular endothelial growth factor (VEGF) secretion by CAFs
and matrix sequestration. Collectively, these findings enhance our understanding
of the mechanisms by which Fn and Col I synergistically interplay in promoting a
sustained altered signaling cascade to remodel the breast tumor stroma for
invasive breast tumor growth.
PMID- 27503586
TI - Brain enhancer activities at the gene-poor 5p14.1 autism-associated locus.
AB - Due to the vast clinical and genetic heterogeneity, identification of causal
genetic determinants for autism spectrum disorder (ASD) has proven to be complex.
Whereas several dozen 'rare' genetic variants for ASD susceptibility have been
identified, studies are still underpowered to analyse 'common' variants for their
subtle effects. A recent application of genome-wide association studies (GWAS) to
ASD indicated significant associations with the single nucleotide polymorphisms
(SNPs) on chromosome 5p14.1, located in a non-coding region between cadherin10
(CDH10) and cadherin9 (CDH9). Here we apply an in vivo bacterial artificial
chromosome (BAC) based enhancer-trapping strategy in mice to scan the gene desert
for spatiotemporal cis-regulatory activities. Our results show that the ASD
associated interval harbors the cortical area, striatum, and cerebellum specific
enhancers for a long non-coding RNA, moesin pseudogene1 antisense (MSNP1AS)
during the brain developing stages. Mouse moesin protein levels are not affected
by exogenously expressed human antisense RNAs in our transgenic brains,
demonstrating the difficulty in modeling rather smaller effects of common
variants. Our first in vivo evidence for the spatiotemporal transcription of
MSNP1AS however provides a further support to connect this intergenic variant
with the ASD susceptibility.
PMID- 27503588
TI - Vitamin K antagonists after all, or possibly not?
PMID- 27503587
TI - Positive association between waist-to-height ratio and hypertension in
adolescents.
AB - INTRODUCTION: The obesity and overweight epidemic, together with increasing
cardiovascular disease, represent a major public health problem worldwide, and
their occurrence in childhood and adolescence has increased in recent decades.
The objective of this study was to assess the association between waist-to-height
ratio (WHR) and the incidence of hypertension in adolescents. METHODS: We
performed a cross-sectional study of adolescents aged 10-17 years of both sexes
attending municipal schools in inland Rio Grande do Sul, Brazil. Using a
secondary database, weight and height measurements, blood pressure, and waist
circumference (WC) were analyzed and body mass index (BMI) and WHR were
calculated. Blood pressure was classified according to the Brazilian hypertension
guidelines, BMI according to the curves of the World Health Organization, and WC
according to Taylor et al. The cutoff used for WHR was 0.50 for both sexes.
RESULTS: Of the 1030 adolescents studied, 29.6% (305) presented
overweight/obesity and 30.4% (313) had hypertension; 24% (247) had high WC and
18.3% (189) presented high WHR. Participants with WHR >=0.50 were 2.4 times more
likely to have hypertension than those with WHR <0.50 (OR 2.39; 95% CI 1.73-3.32;
p<0.001). CONCLUSION: A positive association was found between WHR and the
presence of hypertension in adolescents.
PMID- 27503589
TI - Organization and implementation of a cardio-oncology program.
AB - Considerable advances in cancer therapies in recent decades have reshaped the
prognosis of cancer patients. There are now estimated to be over 20 million
cancer survivors in the USA and Europe, numbers unimaginable a few years ago.
However, this increase in survival, along with the aging of the patient
population, has been accompanied by a rise in adverse cardiovascular effects,
particularly when there is a previous history of heart disease. The incidence of
cardiotoxicity continues to grow, which can compromise the effectiveness of
cancer therapy. Cardiotoxicity associated with conventional therapies, especially
anthracyclines and radiation, is well known, and usually leads to left
ventricular dysfunction. However, heart failure represents only a fraction of the
cardiotoxicity associated with newer therapies, which have diverse cardiovascular
effects. There are few guidelines for early detection, prevention and treatment
of cardiotoxicity of cancer treatments, and no well-established tools for
screening these patients. Echocardiography is the method of choice for assessment
of patients before, during and after cancer treatment. It therefore makes sense
to adopt a multidisciplinary approach to these patients, involving cardiologists,
oncologists and radiotherapists, collaborating in the development of new training
modules, and performing clinical and translational research in a cardio-oncology
program. Cardio-oncology is a new frontier in medicine and has emerged as a new
medical subspecialty that concentrates knowledge, understanding, training and
treatment of cardiovascular comorbidities, risks and complications in patients
with cancer in a comprehensive approach to the patient rather than to the
disease.
PMID- 27503590
TI - The HIPOGAIA study: Monitoring of oral anticoagulation with vitamin K antagonists
in the municipality of Gaia.
AB - INTRODUCTION: Anticoagulant therapy is an effective measure in preventing
thromboembolic adverse events. Of the diseases in which this treatment is
indicated, atrial fibrillation (AF) has the highest incidence worldwide, with a
prevalence of 1.5-2%. OBJECTIVES: To assess the quality of monitoring of patients
with non-valvular AF under oral anticoagulation with vitamin K antagonists in
Vila Nova de Gaia healthcare units. METHODS: This was a retrospective
observational analytical study of the population registered at the 37 healthcare
units of the Vila Nova de Gaia and Espinho health center area under oral
anticoagulation with vitamin K antagonists during 2014. The data were collected
using TAONet((r)) software. The variables studied were health units, age, gender,
INR value, time in therapeutic range (TTR) and medication. TTR was calculated for
each patient using the Rosendaal linear interpolation method. It was stipulated
that each patient should have undergone at least six INR measurements. Data were
analyzed using Microsoft Excel((r)) 2010 and SPSS((r)) version 21, using
descriptive and inferential statistical techniques. RESULTS: A total of 479
patients with non-valvular AF were studied, corresponding to 5883 INR tests. Mean
TTR was 67.4+/-6.5%, and 35.3% of patients exhibited poor control (TTR <60%).
DISCUSSION: Our study showed moderate control of coagulation parameters, but
better than in many international clinical trials and in another Portuguese
observational study. Nevertheless, there is still room for improvement in
anticoagulation monitoring in primary health care.
PMID- 27503591
TI - Alcohol septal ablation in obstructive acromegalic hypertrophic cardiomyopathy -
a first case report.
AB - Acromegaly is a rare disease, mostly caused by a growth hormone (GH)-secreting
benign pituitary tumor, with an increased production of GH and insulin-like
growth factor 1 (IGF-1). Cardiovascular complications are common and are
associated with cardiomyocyte apoptosis and concentric cardiac hypertrophy.
Suppression of GH and IGF-1 appears to improve cardiac function only in the short
term, with little or no decrease in left ventricular mass or improvement in
cardiac function after prolonged treatment. Alcohol septal ablation (ASA) has
emerged as a minimally invasive alternative to septal myectomy, with significant
improvement in symptoms, gradients and left ventricular remodeling. In this
report, we describe the case of a 73-year-old woman with acromegaly due to a
pituitary adenoma diagnosed and treated surgically at the age of 38 but with
recurrence and reoperation at the age of 50. She was referred to our cardiology
department due to a three-month history of progressively worsening exercise
induced dyspnea and orthopnea under optimal medical therapy. Echocardiography and
magnetic resonance imaging revealed severe basal hypertrophy of the
interventricular septum (19 mm), dynamic left ventricular outflow tract
obstruction with a gradient of 70 mmHg at rest and 120 mmHg with Valsalva
maneuver, and systolic anterior movement (SAM). Genetic testing excluded the most
frequent forms of familial hypertrophic cardiomyopathy. ASA was performed with
injection of 2 cc of alcohol in the first septal branch of the left coronary
artery, without complications. At one-year reassessment, significant clinical and
echocardiographic improvement was noted, with disappearance of SAM. To our
knowledge, there have been no previously reported cases of ASA in hypertrophic
cardiomyopathy due to acromegaly. We report a case of successful ASA in
acromegalic cardiomyopathy.
PMID- 27503592
TI - Intake of antioxidant nutrients and coefficients of variation in pregnant women
with preeclampsia.
AB - INTRODUCTION AND OBJECTIVE: Oxidative stress appears to play a critical role in
the pathogenesis of preeclampsia. Evidence suggests that adequate intake of
antioxidants can modulate this condition. The objective of this study was to
assess the intake of antioxidant nutrients and coefficients of variation in
pregnant women with preeclampsia. METHODS: In a cross-sectional study in the
public health network of the city of Maceio, Brazil, a dietary survey was
performed consisting of 24-hour food recalls, with subsequent adjustment of
nutrients using the estimated average requirement as the cutoff point, and a
questionnaire on frequency of consumption of antioxidants. RESULTS: We studied 90
pregnant women with preeclampsia (PWP) and 90 pregnant women without preeclampsia
(PWoP) with mean ages of 25.8+/-6.7 years and 24.1+/-6.2 years (p=0.519),
respectively. A low mean intake of antioxidants (vitamin A, selenium, zinc and
copper) was observed in both PWP and PWoP, although intakes of vitamin A
(p=0.045) and selenium (p=0.008) were higher in PWoP. In addition, we observed
high coefficients of variation in nutrient intakes in both groups, which were
higher for vitamin C (p<0.001), vitamin A (p=0.006) and copper (p=0.005) in PWP.
CONCLUSIONS: Consumption of antioxidant nutrients by pregnant women with
preeclampsia is inadequate, with considerable daily variations in intake, which
points to a need for nutrition education strategies aimed at improving intakes,
because diet is without doubt a key factor in the modulation of oxidative stress
caused by preeclampsia.
PMID- 27503593
TI - High prevalence of clade 8 Escherichia coli O157:H7 isolated from retail meat and
butcher shop environment.
AB - Escherichia coli O157:H7 is an enteric pathogen associated with food safety
threats and with significant morbidity and mortality worldwide. In Argentina,
post-enteric hemolytic uremic syndrome (HUS) is endemic, with >70% of cases
associated with E. coli O157 infection. To date the biological basis behind the
severity among E. coli O157 infections is unknown. However, single nucleotide
polymorphism (SNP) typing has helped to define nine E. coli O157:H7 clades, of
which clade 8 strains are associated with severe disease cases. The aim of this
study was to characterize a collection of 20 STEC O157:H7 strains isolated
between 2011 and 2013 from ground beef and different environmental samples from
butcher shops of Argentina. All strains harbored the eae, ehxA, fliCH7, efa, iha,
and toxB genes, with stx2a/stx2c as the predominant genotype (75%). The XbaI-PFGE
analysis showed that the E. coli O157 strains had high genetic diversity. Nine
strains were grouped in four XbaI-PFGE clusters, whereas 11 strains showed unique
XbaI-PFGE patterns. In contrast, the SNP analysis allowed us to separate the
strains in two distinct lineages representing clade 8 (70%) and clade 6 (30%).
Our results show the molecular characterization of E. coli O157 strains isolated
from ground beef and environmental samples from Argentinean butcher shops.
PMID- 27503594
TI - Molecular characterisation and genetic variation of Elephant Endotheliotropic
Herpesvirus infection in captive young Asian elephants in Thailand.
AB - Elephant Endotheliotropic Herpesvirus (EEHV) is emerging as a new threat for
elephant conservation, since being identified as the cause of severe, often
fatal, haemorrhagic disease in young Asian elephants. To describe positive cases
and the molecular relatedness of virus detected in elephants in Thailand, we re
examined all available of EEHV samples occurring in young elephants in Thailand
between 2006 and 2014 (n=24). Results indicated 75% (18/24) of suspected cases
were positive for EEHV by semi-nested PCR. Further gene analysis identified these
positive cases as EEHV1A (72%, 13/18 cases), EEHV1B (11%, 2/18) and EEHV4 (17%,
3/18). This study is the first to phylogenetically analyse and provide an
overview of most of the known EEHV cases that have occurred in Thailand. Positive
individuals ranged in age from one to nine years, with no sex association
detected, and occurred across geographical locations throughout the country. All
individuals, except one, were captive-born. No history of direct contact among
the cases was recorded, and this together with the fact that various subtype
clusters of virus were found, implied that none of the positive cases were
epidemiologically related. These results concur with the hypothesis that EEHV1 is
likely to be an ancient endogenous pathogen in Asian elephants. It is recommended
that active surveillance and routine monitoring for EEHV should be undertaken in
all elephant range countries, to gain a better understanding of the epidemiology,
transmission and prevention of this disease.
PMID- 27503595
TI - Identification of vaginal bacteria diversity and it's association with clinically
diagnosed bacterial vaginosis by denaturing gradient gel electrophoresis and
correspondence analysis.
AB - Bacterial vaginosis (BV) is a common complex associated with numerous adverse
health outcomes, affecting women of different ages throughout the world. The
etiology of BV remains poorly understood due to the difficulty of establishing a
molecular genetic criterion to recognize the vaginal microbiota of BV-positive
women from that of the normal women. We used techniques of broad-range PCR-DGGE
and gel imaging analysis system cooperated with 16S rRNA gene sequencing and
statistical analysis to investigate the community structure of the healthy and BV
affected vaginal microbial ecosystems. The community of vaginal bacteria detected
in subjects with BV was far more luxuriant and diverse than in subjects without
BV. The mean number of microbial species in 128 BV-positive women was nearly two
times greater than in 68 subjects without BV(4.05+/-1.96 versus 2.59+/-1.14). Our
sequencing efforts yielded many novel phylotypes (198 of our sequences
represented 59 species), including several novel BV-associated bacteria (BVAB)
and many belonging to opportunistic infections, which remain inexplicable for
their roles in determining the health condition of vaginal microflora. This study
identifies Algoriphagus aquatilis, Atopobium vaginae, Burkholderia fungorum,
Megasphaera genomosp species as indicators to BV and subjects with BV harbor
particularly taxon-rich and diverse bacterial communities. Maybe Bifidobacterium,
Staphylococcus or even more alien species are commensal creatures in normal
vaginal microbiota.
PMID- 27503596
TI - Nutrition and health claims on healthy and less-healthy packaged food products in
New Zealand.
AB - Nutrition and health claims are displayed to influence consumers' food choices.
This study assessed the extent and nature of nutrition and health claims on the
front-of-pack of 'healthy' and 'less-healthy' packaged foods in New Zealand.
Foods from eight categories, for which consumption may affect the risk of obesity
and diet-related chronic diseases, were selected from the 2014 Nutritrack
database. The internationally standardised International Network for Food and
Obesity/Non-Communicable Diseases Research, Monitoring and Action Support
(INFORMAS) taxonomy was used to classify claims on packages. The Nutrient
Profiling Scoring Criterion (NPSC) was used to classify products as 'healthy' or
'less healthy'. In total, 7526 products were included, with 47 % (n 3557)
classified as 'healthy'. More than one-third of products displayed at least one
nutrition claim and 15 % featured at least one health claim on the front-of-pack.
Claims were found on one-third of 'less-healthy' products; 26 % of those products
displayed nutrition claims and 7 % featured health claims. About 45 % of
'healthy' products displayed nutrition claims and 23 % featured health claims.
Out of 7058 individual claims, the majority (69 %) were found on 'healthy'
products. Cereals displayed the greatest proportion of nutrition and health
claims (1503 claims on 564 products), of which one-third were displayed on 'less
healthy' cereals. Such claims could be misleading consumers' perceptions of
nutritional quality of foods. It needs to be explored how current regulations on
nutrition and health claims in New Zealand could be further strengthened (e.g.
using the NPSC for nutrition claims, including general health claims as per the
INFORMAS taxonomy) to ensure consumers are protected and not misled.
PMID- 27503598
TI - Signatures of selection and host-adapted gene expression of the Phytophthora
infestans RNA silencing suppressor PSR2.
AB - Phytophthora infestans is a devastating pathogen in agricultural systems.
Recently, an RNA silencing suppressor (PSR2, 'Phytophthora suppressor of RNA
silencing 2') has been described in P. infestans. PSR2 has been shown to increase
the virulence of Phytophthora pathogens on their hosts. This gene is one of the
few effectors present in many economically important Phytophthora species. In
this study, we investigated: (i) the evolutionary history of PSR2 within and
between species of Phytophthora; and (ii) the interaction between sequence
variation, gene expression and virulence. In P. infestans, the highest PiPSR2
expression was correlated with decreased symptom expression. The highest gene
expression was observed in the biotrophic phase of the pathogen, suggesting that
PSR2 is important during early infection. Protein sequence conservation was
negatively correlated with host range, suggesting host range as a driver of PSR2
evolution. Within species, we detected elevated amino acid variation, as observed
for other effectors; however, the frequency spectrum of the mutations was
inconsistent with strong balancing selection. This evolutionary pattern may be
related to the conservation of the host target(s) of PSR2 and the absence of
known corresponding R genes. In summary, our study indicates that PSR2 is a
conserved effector that acts as a master switch to modify plant gene regulation
early during infection for the pathogen's benefit. The conservation of PSR2 and
its important role in virulence make it a promising target for pathogen
management.
PMID- 27503597
TI - Variable proopiomelanocortin expression in tanycytes of the adult rat
hypothalamus and pituitary stalk.
AB - It is generally believed that proopiomelanocortin (POMC) is expressed exclusively
by neurons in the adult rodent brain. Unbeknownst to most researchers, however,
Pomc in situ hybridization studies in the rat show specific labeling in the
ventral wall of the hypothalamic third ventricle, which is formed by specialized
ependymal cells, called tanycytes. Here we characterized this non-neuronal POMC
expression in detail using in situ hybridization and immunohistochemical
techniques, and report two unique characteristics. First, POMC mRNA and precursor
protein expression in non-neuronal cells varies to a great degree as to the
extent and abundance of expression. In brains with low-level expression, POMC
mRNA and protein was largely confined to a population of tanycytes within the
infundibular stalk/caudal median eminence, termed here gamma tanycytes, and a
subset of closely located beta and alpha2 tanycytes. In brains with high-level
expression, POMC mRNA and protein was observed in the vast majority of alpha2,
beta, and gamma tanycytes. This variability was observed in both adult males and
females; of 41 rats between 8 and 15 weeks of age, 17 had low-, 9 intermediate-,
and 15 high-level POMC expression in tanycytes. Second, unlike other known POMC
expressing cells, tanycytes rarely contained detectable levels of
adrenocorticotropin or alpha-melanocyte-stimulating hormone. The results indicate
either a dynamic spatiotemporal pattern whereby low and high POMC syntheses in
tanycytes occur periodically in each brain, or marked interindividual differences
that may persist throughout adulthood. Future studies are required to examine
these possibilities and elucidate the physiologic importance of POMC in
tanycytes. J. Comp. Neurol. 525:411-441, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27503599
TI - BSHI Guideline: HLA matching and donor selection for haematopoietic progenitor
cell transplantation.
AB - A review of the British Society for Histocompatibility and Immunogenetics (BSHI)
"Guideline for selection and HLA matching of related, adult unrelated donors and
umbilical cord units for haematopoietic progenitor cell transplantation" was
undertaken by a BSHI appointed writing committee. Literature searches were
performed, and the data extracted were presented as recommendations according to
the GRADE nomenclature.
PMID- 27503601
TI - Sleep, rhythms and metabolism: too many links to be ignored.
PMID- 27503600
TI - Performance evaluation of a rapid whole-blood immunoassay for the detection of
IgG antibodies against Helicobacter pylori in daily clinical practice.
AB - BACKGROUND: A growing number of rapid Helicobacter pylori antibody tests are
commercially available now, however, some of these tests are often used without
sufficient evaluation. The aim of this study was to evaluate the performance of a
commercially available rapid whole-blood immunoassay (gabControl((r)) H. pylori;
gabmed GmbH, Koln, Germany), for the qualitative detection of IgG antibodies
against H. pylori with the (13)C-urea breath test ((13)C-UBT) serving as a
reference method. METHODS: A total of 108 consecutive outpatients, who were
referred for (13)C-UBT by general practitioners and specialists, were also tested
for H. pylori infection by the gabControl((r)) H. pylori immunoassay. The
clinical performance of this rapid whole-blood test was evaluated by determining
the sensitivity, specificity, positive predictive value (PPV), and negative
predictive value (NPV) compared to the (13)C-UBT. The agreement between the two
tests was calculated using Cohen's Kappa (kappa) with 95 % confidence intervals
(CI). RESULTS: The agreement between the gabControl((r)) H. pylori assay and the
(13)C-UBT was 0.62 [95 % confidence intervals (CIs) 0.47-0.76; P < 0.001]. With
the (13)C-UBT serving as the non-invasive gold standard method of H. pylori
diagnosis, the gabControl((r)) H. pylori assay demonstrated a sensitivity and
specificity of 91.4 and 76.7 %, respectively, with a PPV of 65.3 % and a NPV of
94.9 %. Seventeen (15.7 %) individuals with a positive H. pylori anamnesis showed
a negative (13)C-UBT and were typed positive by the gabControl((r)) H. pylori
assay. Of these, 13 (76.5 %) and 3 individuals (17.6 %) had completed one and two
eradication therapies, respectively. CONCLUSIONS: The gabControl((r)) H. pylori
immunoassay is a rapid and easy to use first line screening tool for H. pylori
IgG antibody detection in daily clinical practice. However, this assay should not
be used for confirmation of the successful H. pylori eradication after antibiotic
treatment.
PMID- 27503602
TI - Vacuolar Chloride Fluxes Impact Ion Content and Distribution during Early
Salinity Stress.
AB - The ability to control the cytoplasmic environment is a prerequisite for plants
to cope with changing environmental conditions. During salt stress, for instance,
Na+ and Cl- are sequestered into the vacuole to help maintain cytosolic ion
homeostasis and avoid cellular damage. It has been observed that vacuolar ion
uptake is tied to fluxes across the plasma membrane. The coordination of both
transport processes and relative contribution to plant adaptation, however, is
still poorly understood. To investigate the link between vacuolar anion uptake
and whole-plant ion distribution during salinity, we used mutants of the only
vacuolar Cl- channel described to date: the Arabidopsis (Arabidopsis thaliana)
ALMT9. After 24-h NaCl treatment, almt9 knock-out mutants had reduced shoot
accumulation of both Cl- and Na+ In contrast, almt9 plants complemented with a
mutant variant of ALMT9 that exhibits enhanced channel activity showed higher Cl-
and Na+ accumulation. The altered shoot ion contents were not based on
differences in transpiration, pointing to a vacuolar function in regulating xylem
loading during salinity. In line with this finding, GUS staining demonstrated
that ALMT9 is highly expressed in the vasculature of shoots and roots. RNA-seq
analysis of almt9 mutants under salinity revealed specific expression profiles of
transporters involved in long-distance ion translocation. Taken together, our
study uncovers that the capacity of vacuolar Cl- loading in vascular cells plays
a crucial role in controlling whole-plant ion movement rapidly after onset of
salinity.
PMID- 27503605
TI - 'Remind-to-move' treatment versus constraint-induced movement therapy for
children with hemiplegic cerebral palsy: a randomized controlled trial.
AB - AIM: To evaluate 'remind-to-move' (RTM) treatment by comparing it with constraint
induced movement therapy (CIMT) and conventional rehabilitation of the upper
extremity in children with hemiplegic cerebral palsy (CP). METHOD: Seventy-three
children (44 males, 29 females; mean age 11y 8mo, standard deviation [SD] 3y 1mo)
- with 20, 38, and 15 in Manual Ability Classification System levels I, II, and
III respectively - were recruited from three special schools and randomly
selected for an RTM (n=25) or CIMT (n=24) programme (for 75h over 3wks) or for
conventional rehabilitation (n=24). The Jebsen-Taylor Hand Function Test, the
Bruininks-Oseretsky Test of Motor Proficiency (Subtest 3), the Caregiver
Functional Use Survey, and arm movement duration captured by accelerometers were
used at the baseline, post-test, and 1-month and 3-month follow-ups. RESULTS:
Both the RTM and CIMT treatments achieved significant gains in manual capacities
and spontaneous hand use immediately after the intervention compared with
conventional rehabilitation, but there were no significant differences between
the two interventions. INTERPRETATION: The RTM treatment demonstrated similar
therapeutic effects with CIMT in manual dexterity and functional hand use, but
both interventions were superior to conventional rehabilitation. RTM is
recommended as an alternative treatment for the hemiplegic upper extremity in
children with CP.
PMID- 27503603
TI - Glutaredoxin GRXS17 Associates with the Cytosolic Iron-Sulfur Cluster Assembly
Pathway.
AB - Cytosolic monothiol glutaredoxins (GRXs) are required in iron-sulfur (Fe-S)
cluster delivery and iron sensing in yeast and mammals. In plants, it is unclear
whether they have similar functions. Arabidopsis (Arabidopsis thaliana) has a
sole class II cytosolic monothiol GRX encoded by GRXS17 Here, we used tandem
affinity purification to establish that Arabidopsis GRXS17 associates with most
known cytosolic Fe-S assembly (CIA) components. Similar to mutant plants with
defective CIA components, grxs17 loss-of-function mutants showed some degree of
hypersensitivity to DNA damage and elevated expression of DNA damage marker
genes. We also found that several putative Fe-S client proteins directly bind to
GRXS17, such as XANTHINE DEHYDROGENASE1 (XDH1), involved in the purine salvage
pathway, and CYTOSOLIC THIOURIDYLASE SUBUNIT1 and CYTOSOLIC THIOURIDYLASE
SUBUNIT2, both essential for the 2-thiolation step of 5-methoxycarbonylmethyl-2
thiouridine (mcm5s2U) modification of tRNAs. Correspondingly, profiling of the
grxs17-1 mutant pointed to a perturbed flux through the purine degradation
pathway and revealed that it phenocopied mutants in the elongator subunit ELO3,
essential for the mcm5 tRNA modification step, although we did not find XDH1
activity or tRNA thiolation to be markedly reduced in the grxs17-1 mutant. Taken
together, our data suggest that plant cytosolic monothiol GRXs associate with the
CIA complex, as in other eukaryotes, and contribute to, but are not essential
for, the correct functioning of client Fe-S proteins in unchallenged conditions.
PMID- 27503604
TI - Chronic Iron Limitation Confers Transient Resistance to Oxidative Stress in
Marine Diatoms.
AB - Diatoms are single-celled, photosynthetic, bloom-forming algae that are
responsible for at least 20% of global primary production. Nevertheless, more
than 30% of the oceans are considered "ocean deserts" due to iron limitation. We
used the diatom Phaeodactylum tricornutum as a model system to explore diatom's
response to iron limitation and its interplay with susceptibility to oxidative
stress. By analyzing physiological parameters and proteome profiling, we defined
two distinct phases: short-term (<3 d, phase I) and chronic (>5 d, phase II) iron
limitation. While at phase I no significant changes in physiological parameters
were observed, molecular markers for iron starvation, such as Iron Starvation
Induced Protein and flavodoxin, were highly up-regulated. At phase II, down
regulation of numerous iron-containing proteins was detected in parallel to
reduction in growth rate, chlorophyll content, photosynthetic activity,
respiration rate, and antioxidant capacity. Intriguingly, while application of
oxidative stress to phase I and II iron-limited cells similarly oxidized the
reduced glutathione (GSH) pool, phase II iron limitation exhibited transient
resistance to oxidative stress, despite the down regulation of many antioxidant
proteins. By comparing proteomic profiles of P. tricornutum under iron limitation
and metatranscriptomic data of an iron enrichment experiment conducted in the
Pacific Ocean, we propose that iron-limited cells in the natural environment
resemble the phase II metabolic state. These results provide insights into the
trade-off between optimal growth rate and susceptibility to oxidative stress in
the response of diatoms to iron quota in the marine environment.
PMID- 27503606
TI - Alginate Sulfate-Nanocellulose Bioinks for Cartilage Bioprinting Applications.
AB - One of the challenges of bioprinting is to identify bioinks which support cell
growth, tissue maturation, and ultimately the formation of functional grafts for
use in regenerative medicine. The influence of this new biofabrication technology
on biology of living cells, however, is still being evaluated. Recently we have
identified a mitogenic hydrogel system based on alginate sulfate which potently
supports chondrocyte phenotype, but is not printable due to its rheological
properties (no yield point). To convert alginate sulfate to a printable bioink,
it was combined with nanocellulose, which has been shown to possess very good
printability. The alginate sulfate/nanocellulose ink showed good printing
properties and the non-printed bioink material promoted cell spreading,
proliferation, and collagen II synthesis by the encapsulated cells. When the
bioink was printed, the biological performance of the cells was highly dependent
on the nozzle geometry. Cell spreading properties were maintained with the lowest
extrusion pressure and shear stress. However, extruding the alginate
sulfate/nanocellulose bioink and chondrocytes significantly compromised cell
proliferation, particularly when using small diameter nozzles and valves.
PMID- 27503608
TI - In vivo assessment of periodontal structures and measurement of gingival sulcus
with Optical Coherence Tomography: a pilot study.
AB - There has been increasing interest on the development of clinically acceptable,
more sensitive and specific methods for non-invasive diagnosis in Periodontics.
In this pilot study, the performance of an Optical Coherence Tomography (OCT)
system in imaging periodontal structures in humans was evaluated. Gingival sulcus
depth measurements were obtained and compared with traditional probes. In total,
445 sites of 23 periodontally healthy individuals were measured by 3 instruments:
North Carolina manual probe, Florida automated probe and OCT at 1325 nm. To
obtain quantitative measurements from OCT images, the gingival refractive index
was also determined. Discomfort/pain perception and the duration of examinations
were compared among the instruments. The analysis of OCT images allowed the
identification of relevant anatomic dental and periodontal regions. The average
sulcus depth measured by OCT, 0.85 +/- 0.27 mm and 0.87 +/- 0.28 mm, was lower
than the values obtained by manual and automated probing. Discomfort/pain were
prevalent for traditional probes, which are invasive methods, than for the non
invasive OCT technique. OCT has the potential to be a reliable tool for in vivo
periodontal tissues evaluation and for reproducible sulcus depth measurements in
healthy sites. Further technological advances are required to reduce the
procedure time and promote evaluation of posterior oral regions. Photonic
assessment of periodontal tissue with OCT (top) in a clinical environment,
showing tooth/gingiva features (bottom).
PMID- 27503607
TI - Protease-Responsive Prodrug with Aggregation-Induced Emission Probe for
Controlled Drug Delivery and Drug Release Tracking in Living Cells.
AB - Controlled drug delivery and real-time tracking of drug release in cancer cells
are essential for cancer therapy. Herein, we report a protease-responsive prodrug
(DOX-FCPPs-PyTPE, DFP) with aggregation-induced emission (AIE) characteristics
for controlled drug delivery and precise tracking of drug release in living
cells. DFP consists of three components: AIE-active tetraphenylethene (TPE)
derivative PyTPE, functionalized cell penetrating peptides (FCPPs) containing a
cell penetrating peptide (CPP) and a short protease-responsive peptide (LGLAG)
that can be selectively cleaved by a cancer-related enzyme matrix
metalloproteinase-2 (MMP-2), and a therapeutic unit (doxorubicin, DOX). Without
MMP-2, this prodrug cannot go inside the cells easily. In the presence of MMP-2,
DFP can be cleaved into two parts. One is cell penetrating peptides (CPPs) linked
DOX, which can easily interact with cell membrane and then go inside the cell
with the help of CPPs. Another is the PyTPE modified peptide which will self
aggregate because of the hydrophobic interaction and turn on the yellow
fluorescence of PyTPE. The appearance of the yellow fluorescence indicates the
release of the therapeutic unit to the cells. The selective delivery of the drug
to the MMP-2 positive cells was also confirmed by using the intrinsic red
fluorescence of DOX. Our result suggests a new and promising method for
controlled drug delivery and real-time tracking of drug release in MMP-2
overexpression cells.
PMID- 27503609
TI - Practice-induced and sequential modulations in the Simon task: evidence from
pupil dilation.
AB - Recent evidence showed that pupil dilation (PD) reflects modulations in the
magnitude of the Simon interference effect due to correspondence sequence. In the
present study we used this measure to assess whether these modulations, thought
to result from cognitive control mechanisms, are influenced by prior practice
with an incompatible stimulus-response (S-R) mapping. To this end, PD and
reaction times (RTs) were recorded while participants performed a Simon task
before and after executing a spatially incompatible practice. The sequential
analysis revealed that PD mirrored the conflict-adaptation pattern observed in
RTs. Crucially, sequential modulations were not affected by prior practice. These
findings support the view that the modulations of the Simon effect due to prior
practice and those due to correspondence sequence result from two different
mechanisms, and suggest that PD can help to better understand the mechanisms
underlying response selection and cognitive control in the Simon task.
PMID- 27503610
TI - Ferromagnetic particles as magnetic resonance imaging temperature sensors.
AB - Magnetic resonance imaging is an important technique for identifying different
types of tissues in a body or spatial information about composite materials.
Because temperature is a fundamental parameter reflecting the biological status
of the body and individual tissues, it would be helpful to have temperature maps
superimposed on spatial maps. Here we show that small ferromagnetic particles
with a strong temperature-dependent magnetization, can be used to produce
temperature-dependent images in magnetic resonance imaging with an accuracy of
about 1 degrees C. This technique, when further developed, could be used to
identify inflammation or tumours, or to obtain spatial maps of temperature in
various medical interventional procedures such as hyperthermia and thermal
ablation. This method could also be used to determine temperature profiles inside
nonmetallic composite materials.
PMID- 27503611
TI - Polygonibacillus indicireducens gen. nov., sp. nov., an indigo-reducing and
obligate alkaliphile isolated from indigo fermentation liquor for dyeing.
AB - Obligately alkaliphilic and halophilic strains, designated In2-9T and D2-7, were
isolated from a fermented Polygonum indigo (Polygonum tinctorium Lour.) liquor
sample obtained from a craft centre in Date City, Hokkaido, Japan. The 16S rRNA
gene sequence phylogeny suggested that strain In2-9T is a member of the genus
Bacillus with the closest relatives being the alkaliphilic species of the genus
Bacillus, Bacillus hemicellulosilyticusJCM 9152T (96.4 % 16S rRNA gene sequence
similarity) and Bacillus alcalophilus DSM 485T (96.5 %). Cells of the isolate
stained Gram-positive and were facultatively anaerobic straight rods that were
motile by peritrichous flagella. Strain In2-9T grew between 13 and 45 degrees C
with optimum growth at approximately 35-37 degrees C. The isolates grew in the
pH range of 8-12 with optimum growth at pH 10. The isoprenoid quinone detected
was menaquinone-6 (MK-6) and the DNA G+C content was 39.4 mol%. The whole-cell
fatty acid profile mainly (>10 %) consisted of iso-C15 : 0, anteiso-C15 : 0 and
C16 : 0. Spore shape and location and chemotaxonomic characteristics revealed
that the isolates were distinctly different from phylogenetic neighbouring
alkaliphilic species of the genus Bacillus. On the basis of phenotypic and
chemotaxonomic characteristics and phylogenetic data, the isolates represent a
novel species of a new genus, for which the name Polygonibacillusindicireducens
gen. nov., sp. nov. is proposed. The type strain of the type species is In2-9T
(=JCM 30831T=NCIMB 14982T), and strain D2-7 is an additional strain of the
species.
PMID- 27503612
TI - Oestrogen-containing contraceptive pills increase vitamin D levels, study finds.
PMID- 27503615
TI - [Long-term complications after appendectomy].
PMID- 27503613
TI - Cardiolipin deficiency causes a dissociation of the b 6 c:caa 3 megacomplex in B.
subtilis membranes.
AB - The associations among respiratory complexes in energy-transducing membranes have
been established. In fact, it is known that the Gram-negative bacteria Paracoccus
denitrificans and Escherichia coli have respiratory supercomplexes in their
membranes. These supercomplexes are important for channeling substrates between
enzymes in a metabolic pathway, and the assembly of these supercomplexes depends
on the protein subunits and membrane lipids, mainly cardiolipin, which is present
in both the mitochondrial inner membrane and bacterial membranes. The Gram
positive bacterium Bacillus subtilis has a branched respiratory chain, in which
some complexes generate proton motive force whereas others constitute an escape
valve of excess reducing power. Some peculiarities of this respiratory chain are
the following: a type II NADH dehydrogenase, a unique b 6 c complex that has a b
6 type cytochrome with a covalently bound heme, and a c-type heme attached to the
third subunit, which is similar to subunit IV of the photosynthetic b 6 f
complex. Cytochrome c oxygen reductase (caa 3 ) contains a c-type cytochrome on
subunit I. We previously showed that the b 6 c and the caa 3 complexes form a
supercomplex. Both the b 6 c and the caa 3 together with the quinol oxygen
reductase aa 3 generate the proton motive force in B. subtilis. In order to seek
proof that this supercomplex is important for bacterial growth in aerobic
conditions we compared the b 6 c: caa 3 supercomplex from wild type membranes
with membranes from two mutants lacking cardiolipin. Both mutant complexes were
found to have similar activity and heme content as the wild type. Clear native
electrophoresis showed that mutants lacking cardiolipin had b 6 c:caa 3
supercomplexes of lower mass or even individual complexes after membrane
solubilization with digitonin. The use of dodecyl maltoside revealed a more
evident difference between wild-type and mutant supercomplexes. Here we provide
evidence showing that cardiolipin plays a role in the stability of the b 6 c:caa
3 supercomplex in B. subtilis.
PMID- 27503614
TI - Fish Oil and Microalga Omega-3 as Dietary Supplements: A Comparative Study on
Cardiovascular Risk Factors in High-Fat Fed Rats.
AB - Dietary supplementation with marine omega-3 polyunsaturated fatty acids (n-3
PUFA) can have beneficial effects on a number of risk factors for cardiovascular
disease (CVD). We compared the effects of two n-3 PUFA rich food supplements
(freeze-dried Odontella aurita and fish oil) on risk factors for CVD. Male rats
were randomly divided into four groups of six animals each and fed with the
following diets: control group (C) received a standard diet containing 7 %
lipids; second group (HF high fat) was fed with a high-fat diet containing 40 %
lipids; third group (HFFO high fat+fish oil) was fed with the high-fat diet
supplemented with 0.5 % fish oil; and fourth group (HFOA high fat+O. aurita)
received the high-fat diet supplemented with 12 % of freeze-dried O. aurita.
After 8 weeks rats fed with the high-fat diet supplemented with O. aurita
displayed a significantly lower bodyweight than those in the other groups. Both
the microalga and the fish oil significantly reduced insulinemia and serum lipid
levels. O. aurita was more effective than the fish oil in reducing hepatic
triacyglycerol levels and in preventing high-fat diet-induced steatosis. O.
aurita and fish oil also reduced platelet aggregation and oxidative status
induced by high fat intake. After an OA supplementation, the adipocytes in the
HFOA group were smaller than those in the HF group. Freeze-dried O. aurita showed
similar or even greater biological effects than the fish oil. This could be
explained by a potential effect of the n-3 PUFA but also other bioactive
compounds of the microalgae.
PMID- 27503616
TI - [Intraoperative ERCP versus laparoscopic bile duct exploration for treatment of
choledocholithiasis].
PMID- 27503617
TI - [Antibiotic treatment versus appendectomy for non-perforated appendicitis :
Results of a meta-analysis].
PMID- 27503618
TI - [Extensive hepatopancreaticobiliary resections including arterial reconstruction
for advanced cholangiocarcinoma].
PMID- 27503619
TI - Hyaluronic acid injection via a pneumatic microjet device to improve forehead
wrinkles.
PMID- 27503620
TI - In vivo uteroplacental release of placental growth factor and soluble Fms-like
tyrosine kinase-1 in normal and preeclamptic pregnancies.
AB - BACKGROUND: Preeclampsia is characterized by maternal endothelial dysfunction,
which underlies a highly diverse clinical presentation. The pathophysiologic
condition remains to be unraveled fully, but interplay between factors that are
released from the placenta and maternal vascular vulnerability is likely. An
imbalance in circulating angiogenic factors is a prominent feature of
preeclampsia; placental growth factor and soluble Fms-like tyrosine kinase 1 have
been implemented as biomarkers of placental function and preeclampsia. Their test
accuracies are limited in a clinical setting, which urges better insight into
their production and removal. Current data suggest that placental growth factor
and soluble Fms-like tyrosine kinase 1 are released from the placenta. Both the
circulating levels and the placental expression are altered in preeclamptic
pregnancies. However, in vivo placental release has not been determined in human
pregnancies. Moreover, there is evidence that extra-placental tissues might
contribute to the circulating levels placental growth factor and soluble Fms-like
tyrosine kinase 1 in normal and preeclamptic pregnancies. OBJECTIVES: We aimed to
study the in vivo placental release of placental growth factor and soluble Fms
like tyrosine kinase 1 by determining the uteroplacental arteriovenous
differences in human pregnancies. Further, we investigated whether this release
was altered in early-onset preeclampsia compared with control subjects and
whether there was a release of placental growth factor and soluble Fms-like
tyrosine kinase 1 from maternal systemic endothelium. STUDY DESIGN: We conducted
a case-control study at Oslo University Hospital and included 23 women with
preeclampsia (diagnosis <34 weeks) and 20 control subjects. During cesarean
delivery, we sampled blood from 3 vessels simultaneously (uterine vein, radial
artery, and antecubital vein). We determined concentrations of placental growth
factor and soluble Fms-like tyrosine kinase 1 and calculated the arteriovenous
differences. A possible net placental and extra-placental release was evaluated
with the use of a Wilcoxon signed rank test. Differences between groups were
compared by a Mann-Whitney U-test. RESULTS: The median gestational age at
delivery was 33.4 weeks (Q1, 28.3; Q3, 34.4 weeks) in the preeclamptic group and
39.3 weeks (Q1, 39.0; Q3, 39.6 weeks) in the control subjects. Women with
preeclampsia had lower plasma concentrations of placental growth factor and
higher concentrations of soluble Fms-like tyrosine kinase 1 compared with control
subjects (P<.001). There were significant uteroplacental arteriovenous
differences of soluble Fms-like tyrosine kinase 1 in preeclampsia (P<.001), but
not in the control subjects. The uteroplacental arteriovenous differences of
placental growth factor were significant in both groups (P<.001). Despite lower
concentrations of plasma placental growth factor in women with preeclampsia, the
arteriovenous differences were not significantly different from normal
pregnancies (P=.53), even when we corrected for placental weight (P=.79). We
found no placental growth factor or soluble Fms-like tyrosine kinase 1
concentration differences between the radial artery and the antecubital vein.
CONCLUSION: Our findings are consistent with a net release of soluble Fms-like
tyrosine kinase 1 from the placenta in early-onset preeclampsia. This study
demonstrated a placental release of placental growth factor to the maternal
circulation but could not demonstrate that this release was impaired in the
preeclamptic group. We could not find evidence of systemic endothelial release of
placental growth factor and soluble Fms-like tyrosine kinase 1 by analyzing the
arteriovenous differences in the forearm. This study contributes to the
pathophysiologic understanding of preeclampsia by the use of the clinical setting
to test current concepts in vivo and underscores that studies of in vivo
degradation rates of placentally released compounds are needed.
PMID- 27503621
TI - First evidence of a menstruating rodent: the spiny mouse (Acomys cahirinus).
AB - BACKGROUND: Advances in research relating to menstruation and associated
disorders (eg, endometriosis and premenstrual syndrome) have been hindered by the
lack of an appropriate animal model. Menstruation, the cyclical shedding of the
decidualized endometrium in the absence of pregnancy, is believed to be limited
to 78 higher-order primates (human beings and Old World monkeys), 4 species of
bat, and the elephant shrew. This represents only 1.5% of the known 5502
mammalian species and <0.09% of these are nonprimates. Thus, many aspects of
menstruation remain poorly understood, limiting the development of effective
treatments for women with menstrual disorders. Menstruation occurs as a
consequence of progesterone priming of the endometrial stroma and a spontaneous
decidual reaction. At the end of each infertile cycle as progesterone levels
decline the uterus is unable to maintain this terminally differentiated stroma
and the superficial endometrium is shed. True menstruation has never been
reported in rodents. OBJECTIVE: Here we describe the first observation of
menstruation in a rodent, the spiny mouse (Acomys cahirinus). STUDY DESIGN:
Virgin female spiny mice (n = 14) aged 12-16 weeks were sampled through daily
vaginal lavage for 2 complete reproductive cycles. Stage-specific collection of
reproductive tissue and plasma was used for histology, prolactin
immunohistochemistry, and enzyme-linked immunosorbent assay of progesterone (n =
4-5/stage of the menstrual cycle). Normally distributed data are reported as the
mean +/- SE and significant differences calculated using a 1-way analysis of
variance. Nonnormal data are displayed as the median values of replicates (with
interquartile range) and significant differences calculated using Kruskal-Wallis
test. RESULTS: Mean menstrual cycle length was 8.7 +/- 0.4 days with red blood
cells observed in the lavages over 3.0 +/- 0.2 days. Cyclic endometrial shedding
and blood in the vaginal canal concluding with each infertile cycle was confirmed
in all virgin females. The endometrium was thickest during the luteal phase at
322.6 MUm (254.8, 512.2), when plasma progesterone peaked at 102.1 ng/mL (70.1,
198.6) and the optical density for prolactin immunoreactivity was strongest
(0.071 +/- 0.01 arbitrary units). CONCLUSION: The spiny mouse undergoes
spontaneous decidualization, demonstrating for the first time menstruation in a
rodent. The spiny mouse provides a readily accessible nonprimate model to study
the mechanisms of menstrual shedding and repair, and may therefore be useful in
furthering studies of human menstrual and pregnancy-associated disorders.
PMID- 27503622
TI - Low self-awareness of osteoporosis and fracture risk among postmenopausal women.
AB - Postmenopausal women with a high risk of fractures may not perceive their risk.
This study showed no concordance between the perceived and calculated risk of
fracture. Almost 80 % of the women identified as a high risk of fracture by the
FRAX algorithm tool perceived themselves to have little risk. PURPOSE: This study
aimed to assess the concordance between self-perception of osteoporosis and
fracture risk and the 10-year risk of fractures calculated by the FRAX algorithm.
METHODS: A cross-sectional study was conducted in Santa Maria, RS, Brazil,
between March 1 and August 31, 2013. Postmenopausal women over 55 years of age
who have had at least one appointment at primary care in the 2 years prior to the
enrolment were recruited. We excluded women with cognitive impairment. A
standardized questionnaire regarding the perception of personal risk of
osteoporosis and fractures was used. We also evaluated previous fractures, family
history of fracture, smoking, alcohol consumption, use of glucocorticoids, and
secondary causes of osteoporosis. Weight and height of the participants were
measured. The risk of fractures of each participant was calculated using the FRAX
algorithm (Fracture Risk Assessment Tool). RESULTS: Of the 1301 invited women,
1057 completed the survey. The average (mean [SD]) age and BMI were 67.2 (7.6)
years and 29.3 (5.5) kg/m(2), respectively. Only 16.9 and 19.9 % participants
believed themselves to be at a high risk of osteoporosis and fractures,
respectively. There was no agreement between the perceived risk of fractures and
the calculated FRAX risk of fractures. Moreover, almost 79.3 % of the women
identified with a high risk of fractures by the FRAX algorithm perceived
themselves as having little risk. CONCLUSION: These results show that
postmenopausal women underestimate their risk of osteoporotic fractures when
compared with their 10-year fracture risk according to FRAX algorithm.
PMID- 27503623
TI - Elevated ferritin and circulating osteoprotegerin levels as independent
predictors of hip fracture in postmenopausal women admitted for fragility
fracture: time for new screening strategies?
AB - Identification of risk factors may help us to understand the pathogenesis of
osteoporotic hip fracture as well as to formulate development of better
diagnostic, prevention and treatment strategies. The present study was designed
to determine the impact of multiple metabolic risk factors such as markers of
systemic inflammation (C-reactive protein), immune responses-acute phase
reactants (ferritin), insulin resistance (HOMA-IR) and bone remodeling
(osteoprotegerin), for the prediction of hip fractures in postmenopausal
osteoporotic women. The study group consisted of 115 postmenopausal women divided
into two groups: Group 1 consisted of 49 women hospitalized in the Orthopedic
Department, Wolfson Medical Center for the diagnosis of non-traumatic hip
fracture and Group 2 contained 66 postmenopausal osteoporotic women without a
history of hip fracture. Metabolic parameters were determined. Circulating OPG
was significantly higher in Group 1 than in Group 2 (205.2 +/- 177.1 vs 60.0 =/
22.3, p < 0.0001). While levels of hemoglobin (Hbg) as well as MCV and MCH did
not differ between groups, circulating ferritin was significantly increased in
Group 1 compared to the control Group 2 (217.9 +/- 195.1 vs 49.7 +/- 31.3, p <
0.0001). In multiple linear regression analysis, which explains about 40 % of the
variability in CRP, 42 % in OPG, and 28 % in ferritin, significant by-group
differences in terms of these parameters persisted even after adjustment.
Elevated serum ferritin concentrations and bone remodeling marker,
osteoprotegerin, are independent predictors of hip fracture in postmenopausal
women hospitalized for fragility fracture.
PMID- 27503626
TI - Analysis of the improvement of selenite retention in smectite by adding alumina
nanoparticles.
AB - Smectite clay is used as barrier for hazardous waste retention and confinement.
It is a powerful material to retain cations, but less effective for retaining
anionic species like selenite. This study shows that the addition of a small
percentage of gamma-Al2O3 nanoparticles to smectite significantly improves
selenite sorption. gamma-Al2O3 nanoparticles provide high surface area and
positively charged surface sites within a wide range of pH, since their point of
zero charge is at pH8-9. An addition of 20wt% of gamma-Al2O3 to smectite is
sufficient to approach the sorption capacity of pure alumina. To analyze the
sorption behavior of the smectite/oxide mixtures, a nonelectrostatic surface
complexation model was considered, accounting for the surface complexation of
HSeO3- and SeO32-, the anion competition, and the formation of surface ternary
complexes with major cations present in the solution. Selenite sorption in
mixtures was satisfactorily described with the surface parameters and
complexation constants defined for the pure systems, accounting only for the
mixture weight fractions. Sorption in mixtures was additive despite the particle
heteroaggregation observed in previous stability studies carried out on
smectite/gamma-Al2O3 mixtures.
PMID- 27503625
TI - Severe somatoform and dysautonomic syndromes after HPV vaccination: case series
and review of literature.
AB - Human papilloma virus (HPV) is recognized as a major cause for cervical cancer
among women worldwide. Two HPV vaccines are currently available: Gardasil(r) and
Cervarix(r). Both vaccines enclose viral antigenic proteins, but differ as to the
biological systems of culture and the adjuvant components. Recently, a collection
of symptoms, indicating nervous system dysfunction, has been described after HPV
vaccination. We retrospectively described a case series including 18 girls (aged
12-24 years) referred to our "Second Opinion Medical Network" for the evaluation
of "neuropathy with autonomic dysfunction" after HPV vaccination. All girls
complained of long-lasting and invalidating somatoform symptoms (including
asthenia, headache, cognitive dysfunctions, myalgia, sinus tachycardia and skin
rashes) that have developed 1-5 days (n = 11), 5-15 days (n = 5) and 15-20 days
(n = 2) after the vaccination. These cases can be included in the recently
described immune dysfunction named autoimmune/inflammatory syndrome induced by
adjuvants (ASIA). HPV vaccine, through its adjuvant component, is speculated to
induce an abnormal activation of the immune system, involving glia cells in the
nervous system too. Further researches should aim at defining the pathological
and clinical aspects of these post-vaccination diseases and identifying a genetic
background predisposing to these adverse reactions.
PMID- 27503624
TI - cDNA phage display for the discovery of theranostic autoantibodies in rheumatoid
arthritis.
AB - Rheumatoid arthritis (RA) is the world's most common autoimmune disease mainly
characterized by a chronic inflammation of multiple synovial joints.
Rheumatologists now have a whole range of treatment options including
glucocorticoids (GCs), classical synthetic and biological disease-modifying
antirheumatic drugs (cs- and bDMARDS), resulting in a tremendous improvement in
treatment outcomes for RA patients over the last two decades. Despite this
progress, the choice of treatment regimen to achieve stable remission at the
individual patient level still largely depends on trial and error. In this
review, the need for novel theranostic markers that can predict a patient's
response to methotrexate, the standard first-line csDMARD treatment, is
discussed. Like in many autoimmune diseases, the majority of RA patients form a
whole range of autoantibodies. We aim to find novel theranostic autoantibody
markers using serological antigen selection, a high-throughput technique that
uses cDNA phage display to identify novel antigen targets. We have constructed a
barcoded cDNA phage display library from the synovial tissue of three RA patients
by fusing cDNA products to the filamentous phage minor coat protein VI. This
library contains a large proportion of full-length genes and gene fragments that
are cloned in frame with the phage gene VI. By screening this library for
antibody reactivity in serum samples of patients from the CareRA trial, which
compared different intensive treatment strategies based on csDMARDs and a step
down GC schedule, our cDNA phage display library has great potential for the
discovery of novel theranostic autoantibody biomarkers.
PMID- 27503627
TI - Drought and detritivores determine leaf litter decomposition in calcareous
streams of the Ebro catchment (Spain).
AB - Drought, an important environmental factor affecting the functioning of stream
ecosystems, is likely to become more prevalent in the Mediterranean region as a
consequence of climate change and enhanced water demand. Drought can have
profound impacts on leaf litter decomposition, a key ecosystem process in
headwater streams, but there is still limited information on its effects at the
regional scale. We measured leaf litter decomposition across a gradient of
aridity in the Ebro River basin. We deployed coarse- and fine-mesh bags with
alder and oak leaves in 11 Mediterranean calcareous streams spanning a range of
over 400km, and determined changes in discharge, water quality, leaf-associated
macroinvertebrates, leaf quality and decomposition rates. The study streams were
subject to different degrees of drought, specific discharge (Ls-1km-2) ranging
from 0.62 to 9.99. One of the streams dried out during the experiment, another
one reached residual flow, whereas the rest registered uninterrupted flow but
with different degrees of flow variability. Decomposition rates differed among
sites, being lowest in the 2 most water-stressed sites, but showed no general
correlation with specific discharge. Microbial decomposition rates were not
correlated with final nutrient content of litter nor to fungal biomass. Total
decomposition rate of alder was positively correlated to the density and biomass
of shredders; that of oak was not. Shredder density in alder bags showed a
positive relationship with specific discharge during the decomposition
experiment. Overall, the results point to a complex pattern of litter
decomposition at the regional scale, as drought affects decomposition directly by
emersion of bags and indirectly by affecting the functional composition and
density of detritivores.
PMID- 27503628
TI - The effect of periphyton on seed germination and seedling growth of rice (Oryza
sativa) in paddy area.
AB - Periphyton is widely distributed in paddy fields and its interactions with paddy
soil and rice growth have been reported rarely. In this study, model paddy
ecosystems with different additional soil substrates were simulated under
controlled conditions to investigate the effects of periphyton on rice seed
germination and seedling growth. Results show that the selected soil substrates
had significant effects on the metabolic activities and growth of periphyton in
paddy fields. The addition of straw to soil enhances but the addition of biochar
leads to attenuation of periphyton growth. The presence of periphyton in the
paddy system, especially with straw in soil greatly increased the germination
index of rice seed (by maximally 21%). However, the biochar treatment in the
presence of periphyton was detrimental for the seed vitality with a decrease of
30%. As a result, the periphyton cover on paddy soil surface significantly
inhibited the growth of rice seedling, including rice height, leaf width and
biomass. To summarize, this study indicates that the presence of periphyton
during seed germination period was detrimental for rice growth, but could be used
to control the weed growth. Thus, this study provided insight into understanding
the periphyton-plant relationships with different soil-substrates and also new
approaches to controlling weeds in paddy fields by regulating the growth of
periphyton.
PMID- 27503629
TI - Airborne bacterial contaminations in typical Chinese wet market with live poultry
trade.
AB - : Chinese wet markets with live poultry trade have been considered as major
sources of pathogen dissemination, and sites for horizontal transfer of bacterial
and viral pathogens. In this study, the pathogenic bacteria and antibiotic
resistant genes (ARGs) in air samples collected at a typical Chinese wet market
had been analysis and quantified. Corynebacterium minutissimum and other
pathogenic bacteria accounted for 0.81-8.02% of the whole microbial community in
different air samples. The four ARGs quantified in this study showed a comparable
relative concentration (copies/ng_DNA) with municipal wastewater. Poultry manures
were demonstrated to be important microbial contamination source in wet market,
which was supported by both microbial composition based source tracking and the
quantification of airborne microbial density. A series of Firmicutes and
Bacteroidetes indicators of poultry area contamination were successfully
screened, which will be useful for the more convenient monitoring of airborne
poultry area contamination. Our results indicate bioaerosols acted as important
route for the transmissions of pathogens and ARGs. Continued surveillance of
airborne microbial contamination is required in poultry trade wet market.
PRACTICAL IMPLICATIONS: Urban live poultry markets are important sources of
pathogen dissemination, and sites for horizontal transfer of viral and bacterial
pathogens. In the present field-study, pathogenic bacteria and antibiotic
resistance genes were focused to provide quantitative information on the levels
of microbial contaminations at the indoor air of wet markets. Results
demonstrated that poultry manures were important microbial contamination source
in wet market, and in the meanwhile bioaerosols were identified as important
route for the transmissions of microbial contaminants. A series of Firmicutes and
Bacteroidetes indicators of poultry area contamination were successfully
screened, which will be useful for the more convenient monitoring of airborne
poultry area contamination.
PMID- 27503630
TI - Polychlorinated biphenyls in settled dust from informal electronic waste
recycling workshops and nearby highways in urban centers and suburban industrial
roadsides of Chennai city, India: Levels, congener profiles and exposure
assessment.
AB - Polychlorinated biphenyls (PCBs) were quantified in settled dust collected from
informal electronic waste (e-waste) recycling workshops and nearby highways in
the urban centers and roadside dust from the suburban industrial belt of Chennai
city in India. Further dust samples were subjected to a high resolution field
emission scanning electron microscope equipped with an energy dispersive X-ray
spectrometer (FESEM/EDX) to characterize the shape, size and elemental
composition of the dust particles. Geomean of total PCB concentration followed
the following order: informal e-waste metal recovery workshops (53ngg-1)>e-waste
dismantling sites (3.6ngg-1)>nearby highways (1.7ngg-1)>suburban industrial
roadsides (1.6ngg-1). In e-waste workshops, tetra, penta and hexa-PCB homologs
contributed two third of Sigma26PCB concentration. Informal e-waste recycling
workshops contributed more than 80% concentration of all the PCB congeners loaded
in the first principal component. Predominance of dioxin like PCBs, PCB-l14, -118
and -126 in the e-waste metal recovery sites were presumably due to combustion
and pyrolytic processes performed during recycling of electrical components.
According to the morphology and elemental composition, settled dust from e-waste
workshops were irregular particles heavily embedded with toxic metals and
industrial roadside dust were distinct angular particles. FESEM revealed that
average particle size (in Ferret diameter) increased in the following order: e
waste recycling workshops (0.5MUm)= 3 and n >= 3) quantum system. In
particular, we give so far the smallest number of locally indistinguishable
states of a completable orthogonal product basis in arbitrary quantum systems.
Furthermore, we construct a series of small and locally indistinguishable
orthogonal product bases in m ? n (m >= 3 and n >= 3). All the results lead to a
better understanding of the structures of locally indistinguishable product bases
in arbitrary bipartite quantum system.
PMID- 27503635
TI - Detecting the Biopolymer Behavior of Graphene Nanoribbons in Aqueous Solution.
AB - Graphene nanoribbons (GNR), can be prepared in bulk quantities for large-area
applications by reducing the product from the lengthwise oxidative unzipping of
multiwalled carbon nanotubes (MWNT). Recently, the biomaterials application of
GNR has been explored, for example, in the pore to be used for DNA sequencing.
Therefore, understanding the polymer behavior of GNR in solution is essential in
predicting GNR interaction with biomaterials. Here, we report experimental
studies of the solution-based mechanical properties of GNR and their parent
products, graphene oxide nanoribbons (GONR). We used atomic force microscopy
(AFM) to study their mechanical properties in solution and showed that GNR and
GONR have similar force-extension behavior as in biopolymers such as proteins and
DNA. The rigidity increases with reducing chemical functionalities. The
similarities in rigidity and tunability between nanoribbons and biomolecules
might enable the design and fabrication of GNR-biomimetic interfaces.
PMID- 27503637
TI - Issues in Pain Prediction - More Gain than Pain.
PMID- 27503636
TI - Maternal methylmercury exposure through rice ingestion and offspring
neurodevelopment: A prospective cohort study.
AB - BACKGROUND: Dietary methylmercury intake can occur not only through fish
ingestion but also through rice ingestion; however, rice does not contain the
same beneficial micronutrients as fish. OBJECTIVES: In rural China, where rice is
a staple food, associations between prenatal methylmercury exposure (assessed
using maternal hair mercury) and impacts on offspring neurodevelopment were
investigated. METHODS: A total of 398 mothers were recruited at parturition at
which time a sample of scalp hair was collected. Offspring (n=270, 68%) were
assessed at 12 months using the Bayley Scales of Infant Development-II, yielding
age-adjusted scores for the Mental Developmental Index (MDI) and Psychomotor
Developmental Index (PDI). RESULTS: Among 270 mothers, 85% ingested rice daily,
41% never or rarely ingested fish/shellfish and 11% ingested fish/shellfish at
least twice/weekly. Maternal hair mercury averaged 0.41MUg/g (median: 0.39MUg/g,
range: 0.079-1.7MUg/g). In unadjusted models, offspring neurodevelopment (both
MDI and PDI) was inversely correlated with hair mercury. Associations were
strengthened after adjustment for fish/shellfish ingestion, rice ingestion, total
energy intake (kcal), and maternal/offspring characteristics for both the MDI
[Beta: -4.9, 95% Confidence Interval (CI): -9.7, -0.12] and the PDI (Beta: -2.7,
95% CI: -8.3, 2.9), although confidence intervals remained wide for the latter.
CONCLUSIONS: For 12-month old offspring living in rural China, prenatal
methylmercury exposure was associated with statistically significant decrements
in offspring cognition, but not psychomotor development. Results expose potential
new vulnerabilities for communities depending on rice as a staple food.
PMID- 27503638
TI - High Prevalence of Carbapenemase-Producing Enterobacteriaceae among Hospitalized
Children in Luanda, Angola.
AB - This study aimed to evaluate the prevalence of carbapenemase-producing
Enterobacteriaceae in Luanda, Angola. A total of 157 rectal samples were
collected from children visiting a pediatric hospital in Luanda in March 2015.
Fifty-seven imipenem-nonsusceptible enterobacterial isolates were recovered, most
of which were non-clonally related. The blaOXA-181 (50/57) and blaNDM-1 (7/57)
carbapenemase genes were identified. Notably, OXA-181-producing Escherichia coli
isolates rarely coproduced extended-spectrum beta-lactamases and consequently
remained susceptible to broad-spectrum cephalosporins. The blaOXA-181 gene was
always located on an IncX3 plasmid, while the blaNDM-1 gene was located on either
IncFIA or IncA/C plasmids. The study identified a high prevalence of OXA-181
among hospitalized children in Angola.
PMID- 27503639
TI - The Synergistic Effect of Azoles and Fluoxetine against Resistant Candida
albicans Strains Is Attributed to Attenuating Fungal Virulence.
AB - This study evaluated the synergistic effects of the selective serotonin reuptake
inhibitor, fluoxetine, in combination with azoles against Candida albicans both
in vitro and in vivo and explored the underlying mechanism. MICs, sessile MICs,
and time-kill curves were determined for resistant C. albicans Galleria
mellonella was used as a nonvertebrate model for determining the efficacy of the
drug combinations against C. albicans in vivo For the mechanism study, gene
expression levels of the SAP gene family were determined by reverse transcription
(RT)-PCR, and extracellular phospholipase activities were detected in vitro by
the egg yolk agar method. The combinations resulted in synergistic activity
against C. albicans strains, but the same effect was not found for the non
albicans Candida strains. For the biofilms formed over 4, 8, and 12 h, synergism
was seen for the combination of fluconazole and fluoxetine. In addition, the time
kill curves confirmed the synergism dynamically. The results of the G. mellonella
studies agreed with the in vitro analysis. In the mechanism study, we observed
that fluconazole plus fluoxetine caused downregulation of the gene expression
levels of SAP1 to SAP4 and weakened the extracellular phospholipase activities of
resistant C. albicans The combinations of azoles and fluoxetine showed
synergistic effects against resistant C. albicans may diminish the virulence
properties of C. albicans.
PMID- 27503641
TI - Development of an In Vitro Assay for Detection of Drug-Induced Resuscitation
Promoting-Factor-Dependent Mycobacteria.
AB - Tuberculosis is a major infectious disease that requires prolonged chemotherapy
with a combination of four drugs. Here we present data suggesting that treatment
of Mycobacterium tuberculosis, the causative agent of tuberculosis, and
Mycobacterium smegmatis, a model organism widely used for the screening of
antituberculosis agents, with first-line drugs resulted in the generation of
substantial populations that could be recovered only by the addition of a culture
supernatant from growing mycobacteria. These bacilli failed to grow in standard
media, resulting in significant underestimation of the numbers of viable
mycobacteria in treated samples. We generated M. smegmatis strains overexpressing
M. tuberculosis resuscitation-promoting factors (Rpfs) and demonstrated their
application for the detection of Rpf-dependent mycobacteria generated after drug
exposure. Our data offer novel opportunities for validation of the sterilizing
activity of antituberculosis agents.
PMID- 27503640
TI - Preclinical Profile and Clinical Efficacy of a Novel Hepatitis C Virus NS5A
Inhibitor, EDP-239.
AB - EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural
protein 5A (NS5A), has been investigated in vitro and in vivo EDP-239 is a
potent, selective inhibitor with potency at picomolar to nanomolar concentrations
against HCV genotypes 1 through 6. In the presence of human serum, the potency of
EDP-239 was reduced by less than 4-fold. EDP-239 is additive to synergistic with
other direct-acting antivirals (DAAs) or host-targeted antivirals (HTAs) in
blocking HCV replication and suppresses the selection of resistance in vitro
Furthermore, EDP-239 retains potency against known DAA- or HTA-resistant
variants, with half-maximal effective concentrations (EC50s) equivalent to those
for the wild type. In a phase I, single-ascending-dose, placebo-controlled
clinical trial, EDP-239 demonstrated excellent pharmacokinetic properties that
supported once daily dosing. A single 100-mg dose of EDP-239 resulted in
reductions in HCV genotype 1a viral RNA of >3 log10 IU/ml within the first 48 h
after dosing and reductions in genotype 1b viral RNA of >4-log10 IU/ml within 96
h. (This study has been registered at ClinicalTrials.gov under identifier
NCT01856426.).
PMID- 27503642
TI - Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of
a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.
AB - This study aimed to investigate the pharmacokinetics (PK), safety, and
tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A
phase I, multicenter, open-label PK study was conducted in pediatric patients
hospitalized with an infection and receiving systemic antibiotic therapy.
Patients were enrolled into four age cohorts (cohort 1, >=12 to <18 years; cohort
2, >=6 to <12 years; cohort 3, >=2 to <6 years; cohort 4, >=3 months to <2
years). Patients received a single 2-h intravenous infusion of ceftazidime
avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [>=40 kg] or 50
to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were
collected to describe individual PK characteristics for ceftazidime and
avibactam. Population PK modeling was used to describe characteristics of
ceftazidime and avibactam PK across all age groups. Safety and tolerability were
assessed. Thirty-two patients received study drug. Mean plasma concentration-time
curves, geometric mean maximum concentration (Cmax), and area under the
concentration-time curve from time zero to infinity (AUC0-infinity) were similar
across all cohorts for both drugs. Six patients (18.8%) reported an adverse
event, all mild or moderate in intensity. No deaths or serious adverse events
occurred. The single-dose PK of ceftazidime and avibactam were comparable between
each of the 4 age cohorts investigated and were broadly similar to those
previously observed in adults. No new safety concerns were identified. (This
study has been registered at ClinicalTrials.gov under registration no.
NCT01893346.).
PMID- 27503643
TI - Effects of Lipid-Lowering Drugs on Vancomycin Susceptibility of Mycobacteria.
AB - Tuberculosis is still a cause of major concern, partly due to the emergence of
multidrug-resistant strains. New drugs are therefore needed. Vancomycin can
target mycobacteria with cell envelope deficiency. In this study, we used a
vancomycin susceptibility assay to detect drugs hampering lipid synthesis in
Mycobacterium bovis BCG and in Mycobacterium tuberculosis We tested three drugs
already used to treat human obesity: tetrahydrolipstatin (THL), simvastatin, and
fenofibrate. Only vancomycin and THL were able to synergize on M. bovis BCG and
on M. tuberculosis, although mycobacteria could also be inhibited by simvastatin
alone. Lipid analysis allowed us to identify several lipid modifications in M.
tuberculosis H37Rv treated with those drugs. THL treatment mainly reduced the
phthiocerol dimycocerosate (PDIM) content in the mycobacterial cell wall,
providing an explanation for the synergy, since PDIM deficiency has been related
to vancomycin susceptibility. Proteomic analysis suggested that bacteria treated
with THL, in contrast to bacteria treated with simvastatin, tried to recover,
inducing, among other reactions, lipid synthesis. The combination of THL and
vancomycin should be considered a promising solution in developing new strategies
to treat multidrug-resistant tuberculosis.
PMID- 27503644
TI - Preclinical and Clinical Resistance Profile of EDP-239, a Novel Hepatitis C Virus
NS5A Inhibitor.
AB - EDP-239, a potent and selective hepatitis C virus (HCV) nonstructural protein 5A
(NS5A) inhibitor developed for the treatment of HCV infection, has been
investigated in vitro and in vivo This study sought to characterize genotypic
changes in the HCV NS5A sequence of genotype 1 (GT1) replicons and to compare
those changes to GT1 viral RNA mutations isolated from clinical trial patients.
Resistance selection experiments in vitro using a subgenomic replicon identified
resistance-associated mutations (RAMs) at GT1a NS5A amino acid positions 24, 28,
30, 31, and 93 that confer various degrees of resistance to EDP-239. Key RAMs
were similarly identified in GT1b NS5A at amino acid positions 31 and 93.
Mutations F36L in GT1a and A92V in GT1b do not confer resistance to EDP-239
individually but were found to enhance the resistance of GT1a K24R and GT1b Y93H.
RAMs were identified in GT1 patients at baseline or after dosing with EDP-239
that were similar to those detected in vitro Baseline RAMs identified at NS5A
position 93 in GT1, or positions 28 or 30 in GT1a only, correlated with a reduced
treatment response. RAMs at additional positions were also detected and may have
contributed to reduced EDP-239 efficacy. The most common GT1a and GT1b RAMs found
to persist up to weeks 12, 24, or 48 were those at NS5A positions 28, 30, 31, 58
(GT1a only), and 93. Those RAMs persisting at the highest frequencies up to weeks
24 or 48 were L31M and Q30H/R for GT1a and L31M and Y93H for GT1b. (This study
has been registered at ClinicalTrials.gov under identifier NCT01856426.).
PMID- 27503645
TI - Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir
Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent
Dolutegravir or Abacavir plus Lamivudine.
AB - The direct-acting antiviral regimen of 25 mg ombitasvir-150 mg paritaprevir-100
mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved
for the treatment of hepatitis C virus genotype 1 infection, including patients
coinfected with human immunodeficiency virus. This study was performed to
evaluate the pharmacokinetic, safety, and tolerability effects of coadministering
the regimen of 3 direct-acting antivirals with two antiretroviral therapies
(dolutegravir or abacavir plus lamivudine). Healthy volunteers (n = 24) enrolled
in this phase I, single-center, open-label, multiple-dose study received 50 mg
dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4
days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct
acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10
days. Pharmacokinetic parameters were calculated to compare combination therapy
with 3-direct-acting-antiviral or antiretroviral therapy alone, and
safety/tolerability were assessed throughout the study. Coadministration of the 3
direct-acting-antiviral regimen increased the geometric mean maximum plasma
concentration (Cmax) and the area under the curve (AUC) of dolutegravir by 22%
(central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38%
(1.380 [1.295, 1.469]), respectively. Abacavir geometric mean Cmax and AUC values
decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while
those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876
[0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean Cmax
and AUC during coadministration were within 18% of measurements made during
administration of the 3-direct-acting-antiviral regimen alone, although trough
concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729
[0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively.
All study treatments were generally well tolerated, with no evidence of increased
rates of adverse events during combination administration. These data indicate
that the 3-direct-acting-antiviral regimen can be administered with dolutegravir
or abacavir plus lamivudine without dose adjustment.
PMID- 27503646
TI - Multiple Drug Transporters Are Involved in Renal Secretion of Entecavir.
AB - Entecavir (ETV) is a first-line antiviral agent for the treatment of chronic
hepatitis B virus infection. Renal excretion is the major elimination path of
ETV, in which tubular secretion plays the key role. However, the secretion
mechanism has not been clarified. We speculated that renal transporters mediated
the secretion of ETV. Therefore, the aim of our study was to elucidate which
transporters contribute to the renal disposition of ETV. Our results revealed
that ETV (50 MUM) remarkably reduced the accumulation of probe substrates in MDCK
cells stably expressing human multidrug and toxin efflux extrusion proteins
(hMATE1/2-K), organic cation transporter 2 (hOCT2), and carnitine/organic cation
transporters (hOCTNs) and increased the substrate accumulation in cells
transfected with multidrug resistance-associated protein 2 (hMRP2) or multidrug
resistance protein 1 (hMDR1). Moreover, ETV was proved to be a substrate of the
above-described transporters. In transwell studies, the transport of ETV in MDCK
hOCT2-hMATE1 showed a distinct directionality from BL (hOCT2) to AP (hMATE1), and
the cellular accumulation of ETV in cells expressing hMATE1 was dramatically
lower than that of the mock-treated cells. The accumulation of ETV in mouse
primary renal tubular cells was obviously affected by inhibitors of organic anion
transporter 1/3 (Oat1/3), Oct2, Octn1/2, and Mrp2. Therefore, the renal uptake of
ETV is likely mediated by OAT1/3 and OCT2 while the efflux is mediated by MATEs,
MDR1, and MRP2, and OCTN1/2 may participate in both renal secretion and
reabsorption.
PMID- 27503648
TI - IMP-27, a Unique Metallo-beta-Lactamase Identified in Geographically Distinct
Isolates of Proteus mirabilis.
AB - A novel metallo-beta-lactamase gene, blaIMP-27, was identified in unrelated
Proteus mirabilis isolates from two geographically distinct locations in the
United States. Both isolates harbor blaIMP-27 as part of the first gene cassette
in a class 2 integron. Antimicrobial susceptibility testing indicated
susceptibility to aztreonam, piperacillin-tazobactam, and ceftazidime but
resistance to ertapenem. However, hydrolysis assays indicated that ceftazidime
was a substrate for IMP-27.
PMID- 27503649
TI - Emergence of ileS2-Carrying, Multidrug-Resistant Plasmids in Staphylococcus
lugdunensis.
AB - Of 137 Staphylococcus lugdunensis isolates collected from two nephrology centers
in Hong Kong, 10 (7.3%) and 3 (2.2%) isolates had high-level and low-level
mupirocin resistance, respectively. Isolates with high-level resistance contained
the plasmid-mediated ileS2 gene, while isolates with low-level resistance
contained the mutation V588F within the chromosomal ileS gene. All but one of the
ileS2-positive isolates belong to the predominating clone HKU1. Plasmids carrying
the ileS2 gene were mosaic and also cocarry multiple other resistance
determinants.
PMID- 27503647
TI - Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium
tuberculosis That Target Leucyl-tRNA Synthetase.
AB - The recent development and spread of extensively drug-resistant and totally drug
resistant resistant (TDR) strains of Mycobacterium tuberculosis highlight the
need for new antitubercular drugs. Protein synthesis inhibitors have played an
important role in the treatment of tuberculosis (TB) starting with the inclusion
of streptomycin in the first combination therapies. Although parenteral
aminoglycosides are a key component of therapy for multidrug-resistant TB, the
oxazolidinone linezolid is the only orally available protein synthesis inhibitor
that is effective against TB. Here, we show that small-molecule inhibitors of
aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial
protein synthesis targets, are orally bioavailable and effective against M.
tuberculosis in TB mouse infection models. We applied the oxaborole tRNA-trapping
(OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl
tRNA synthetase (LeuRS), to M. tuberculosis LeuRS. X-ray crystallography was used
to guide the design of LeuRS inhibitors that have good biochemical potency and
excellent whole-cell activity against M. tuberculosis Importantly, their good
oral bioavailability translates into in vivo efficacy in both the acute and
chronic mouse models of TB with potency comparable to that of the frontline drug
isoniazid.
PMID- 27503650
TI - First Report of the Globally Disseminated IncX4 Plasmid Carrying the mcr-1 Gene
in a Colistin-Resistant Escherichia coli Sequence Type 101 Isolate from a Human
Infection in Brazil.
AB - A colistin-resistant Escherichia coli strain was recovered from a patient with a
diabetic foot infection in Brazil. Whole-genome analysis revealed that the E.
coli isolate belonged to the widespread sequence type (ST) 101 and harbored the
mcr-1 gene on an IncX4 plasmid that was highly similar to mcr-1-bearing IncX4
plasmids that were recently identified in Enterobacteriaceae from food, animal,
and human samples recovered on different continents. These results suggest that
self-transmissible IncX4-type plasmids may represent promiscuous plasmids
contributing to the intercontinental spread of the mcr-1 gene.
PMID- 27503652
TI - mcr-1 in Multidrug-Resistant blaKPC-2-Producing Clinical Enterobacteriaceae
Isolates in Singapore.
PMID- 27503651
TI - Nicotiana alata Defensin Chimeras Reveal Differences in the Mechanism of Fungal
and Tumor Cell Killing and an Enhanced Antifungal Variant.
AB - The plant defensin NaD1 is a potent antifungal molecule that also targets tumor
cells with a high efficiency. We examined the features of NaD1 that contribute to
these two activities by producing a series of chimeras with NaD2, a defensin that
has relatively poor activity against fungi and no activity against tumor cells.
All plant defensins have a common tertiary structure known as a cysteine
stabilized alpha-beta motif which consists of an alpha helix and a triple
stranded beta-sheet stabilized by four disulfide bonds. The chimeras were
produced by replacing loops 1 to 7, the sequences between each of the conserved
cysteine residues on NaD1, with the corresponding loops from NaD2. The loop 5
swap replaced the sequence motif (SKILRR) that mediates tight binding with
phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and is essential for the potent
cytotoxic effect of NaD1 on tumor cells. Consistent with previous reports, there
was a strong correlation between PI(4,5)P2 binding and the tumor cell killing
activity of all of the chimeras. However, this correlation did not extend to
antifungal activity. Some of the loop swap chimeras were efficient antifungal
molecules, even though they bound poorly to PI(4,5)P2, suggesting that additional
mechanisms operate against fungal cells. Unexpectedly, the loop 1B swap chimera
was 10 times more active than NaD1 against filamentous fungi. This led to the
conclusion that defensin loops have evolved as modular components that combine to
make antifungal molecules with variable mechanisms of action and that artificial
combinations of loops can increase antifungal activity compared to that of the
natural variants.
PMID- 27503654
TI - Activity of Cysteamine against the Cystic Fibrosis Pathogen Burkholderia cepacia
Complex.
AB - There are no wholly successful chemotherapeutic strategies against Burkholderia
cepacia complex (BCC) colonization in cystic fibrosis (CF). We assessed the
impact of cysteamine (Lynovex) in combination with standard-of-care CF
antibiotics in vitro against BCC CF isolates by the concentration at which 100%
of bacteria were killed (MIC100) and checkerboard assays under CLSI standard
conditions. Cysteamine facilitated the aminoglycoside-, fluoroquinolone- and
folate pathway inhibitor-mediated killing of BCC organisms that were otherwise
resistant or intermediately sensitive to these antibiotic classes. Slow-growing
BCC strains are often recalcitrant to treatment and form biofilms. In assessing
the impact of cysteamine on biofilms, we demonstrated inhibition of BCC biofilm
formation at sub-MIC100s of cysteamine.
PMID- 27503655
TI - Determining the Optimal Carbapenem MIC That Distinguishes Carbapenemase-Producing
and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae.
AB - Carbapenemase-producing (CP) Enterobacteriaceae are largely responsible for the
rapid spread of carbapenem-resistant Enterobacteriaceae (CRE). Distinguishing CP
CRE from non-CP-CRE has important infection control implications. In a cohort of
198 CRE isolates, for isolates that remained susceptible or intermediate to some
carbapenem antibiotics, an ertapenem MIC of 0.5 MUg/ml and meropenem, imipenem,
and doripenem MICs of 2 MUg/ml were best able to distinguish CP-CRE from non-CP
CRE isolates.
PMID- 27503653
TI - A Novel Spirooxindole Derivative Inhibits the Growth of Leishmania donovani
Parasites both In Vitro and In Vivo by Targeting Type IB Topoisomerase.
AB - Visceral leishmaniasis is a fatal parasitic disease, and there is an emergent
need for development of effective drugs against this neglected tropical disease.
We report here the development of a novel spirooxindole derivative, N-benzyl
2,2'alpha-3,3',5',6',7',7alpha,alpha'-octahydro-2methoxycarbonyl-spiro[indole
3,3'-pyrrolizidine]-2-one (compound 4c), which inhibits Leishmania donovani
topoisomerase IB (LdTopIB) and kills the wild type as well as drug-resistant
parasite strains. This compound inhibits catalytic activity of LdTopIB in a
competitive manner. Unlike camptothecin (CPT), the compound does not stabilize
the DNA-topoisomerase IB cleavage complex; rather, it hinders drug-DNA-enzyme
covalent complex formation. Fluorescence studies show that the stoichiometry of
this compound binding to LdTopIB is 2:1 (mole/mole), with a dissociation constant
of 6.65 MUM. Molecular docking with LdTopIB using the stereoisomers of compound
4c produced two probable hits for the binding site, one in the small subunit and
the other in the hinge region of the large subunit of LdTopIB. This spirooxindole
is highly cytotoxic to promastigotes of L. donovani and also induces apoptosis
like cell death in the parasite. Treatment with compound 4c causes depolarization
of mitochondrial membrane potential, formation of reactive oxygen species inside
parasites, and ultimately fragmentation of nuclear DNA. Compound 4c also
effectively clears amastigote forms of wild-type and drug-resistant parasites
from infected mouse peritoneal macrophages but has less of an effect on host
macrophages. Moreover, compound 4c showed strong antileishmanial efficacies in
the BALB/c mouse model of leishmaniasis. This compound potentially can be used as
a lead for developing excellent antileishmanial agents against emerging drug
resistant strains of the parasite.
PMID- 27503656
TI - Gel-Entrapped Staphylococcus aureus Bacteria as Models of Biofilm Infection
Exhibit Growth in Dense Aggregates, Oxygen Limitation, Antibiotic Tolerance, and
Heterogeneous Gene Expression.
AB - An experimental model that mimicked the structure and characteristics of in vivo
biofilm infections, such as those occurring in the lung or in dermal wounds where
no biomaterial surface is present, was developed. In these infections, microbial
biofilm forms as cell aggregates interspersed in a layer of mucus or host matrix
material. This structure was modeled by filling glass capillary tubes with an
agarose gel that had been seeded with Staphylococcus aureus bacteria and then
incubating the gel biofilm in medium for up to 30 h. Confocal microscopy showed
that the bacteria formed in discrete pockets distributed throughout the gel
matrix. These aggregates enlarged over time and also developed a size gradient,
with the clusters being larger near the nutrient- and oxygen-supplied interface
and smaller at greater depths. Bacteria entrapped in gels for 24 h grew slowly
(specific growth rate, 0.06 h(-1)) and were much less susceptible to oxacillin,
minocycline, or ciprofloxacin than planktonic cells. Microelectrode measurements
showed that the oxygen concentration decreased with depth into the gel biofilm,
falling to values less than 3% of air saturation at depths of 500 MUm. An
anaerobiosis-responsive green fluorescent protein reporter gene for lactate
dehydrogenase was induced in the region of the gel where the measured oxygen
concentrations were low, confirming biologically relevant hypoxia. These results
show that the gel biofilm model captures key features of biofilm infection in
mucus or compromised tissue: formation of dense, distinct aggregates, reduced
specific growth rates, local hypoxia, and antibiotic tolerance.
PMID- 27503657
TI - In Vitro Activity of 3-Triazeneindoles against Mycobacterium tuberculosis and
Mycobacterium avium.
AB - Among 230 target-synthesized indole-based compounds, seven 3-triazenoindoles
showed MICs of 0.2 to 0.5 MUg/ml against Mycobacterium tuberculosis strain H37Rv
and isoniazid-resistant human isolate CN-40. The TU112 compound was active also
against a dormant form of M. tuberculosis Some of these triazenoindoles were
active against Mycobacterium avium, with MICs of 0.05 to 0.5 MUg/ml. The
selectivity indices (SI) for M. tuberculosis and M. avium were significantly
higher than 10, making these compounds acceptable for the next testing step.
PMID- 27503658
TI - Increasing Trends in mcr-1 Prevalence among Extended-Spectrum-beta-Lactamase
Producing Escherichia coli Isolates from French Calves despite Decreasing
Exposure to Colistin.
PMID- 27503659
TI - Phase 2, Dose-Ranging Study of Relebactam with Imipenem-Cilastatin in Subjects
with Complicated Intra-abdominal Infection.
AB - Relebactam (REL [MK-7655]) is a novel class A/C beta-lactamase inhibitor intended
for use with imipenem for the treatment of Gram-negative bacterial infections.
REL restores imipenem activity against some resistant strains of Klebsiella and
Pseudomonas In this multicenter, double-blind, controlled trial (NCT01506271),
subjects who were >=18 years of age with complicated intra-abdominal infection
were randomly assigned (1:1:1) to receive 250 mg REL, 125 mg REL, or placebo,
each given intravenously (i.v.) with 500 mg imipenem-cilastatin (IMI) every 6 h
(q6h) for 4 to 14 days. The primary efficacy endpoint was the proportion of
microbiologically evaluable (ME) subjects with a favorable clinical response at
discontinuation of i.v. therapy (DCIV). A total of 351 subjects were randomized,
347 (99%) were treated, and 255 (73%) were ME at DCIV (55% male; mean age, 49
years). The most common diagnoses were complicated appendicitis (53%) and
complicated cholecystitis (17%). Thirty-six subjects (13%) had imipenem-resistant
Gram-negative infections at baseline. Both REL doses plus IMI were generally well
tolerated and demonstrated safety profiles similar to that of IMI alone. Clinical
response rates at DCIV were similar in subjects who received 250 mg REL plus IMI
(96.3%) or 125 mg REL plus IMI (98.8%), and both were noninferior to IMI alone
(95.2%; one-sided P < 0.001). The treatment groups were also similar with respect
to clinical response at early and late follow-up and microbiological response at
all visits. Pharmacokinetic/pharmacodynamic simulations show that imipenem
exposure at the proposed dose of 500 mg IMI with 250 mg REL q6h provides coverage
of >90% of carbapenem-resistant bacterial strains.
PMID- 27503661
TI - Migraine-like headache caused by rheumatic heart disease: The second case of
'Mahler's migraine'?
PMID- 27503660
TI - Genetic characterization of cysteine-rich type-b avenin-like protein coding genes
in common wheat.
AB - The wheat avenin-like proteins (ALP) are considered atypical gluten constituents
and have shown positive effects on dough properties revealed using a transgenic
approach. However, to date the genetic architecture of ALP genes is unclear,
making it impossible to be utilized in wheat breeding. In the current study,
three genes of type-b ALPs were identified and mapped to chromosomes 7AS, 4AL and
7DS. The coding gene sequence of both TaALP-7A and TaALP-7D was 855 bp long,
encoding two identical homologous 284 amino acid long proteins. TaALP-4A was 858
bp long, encoding a 285 amino acid protein variant. Three alleles were identified
for TaALP-7A and four for TaALP-4A. TaALP-7A alleles were of two types: type-1,
which includes TaALP-7A1 andTaALP-7A2, encodes mature proteins, while type-2,
represented byTaALP-7A3, contains a stop codon in the coding region and thus does
not encode a mature protein. Dough quality testing of 102 wheat cultivars
established a highly significant association of the type-1 TaALP-7A allele with
better wheat processing quality. This allelic effects were confirmed among a
range of commercial wheat cultivars. Our research makes the ALP be the first of
such genetic variation source that can be readily utilized in wheat breeding.
PMID- 27503663
TI - Corrigendum to "Generalization of treadmill perturbation to overground slip
during gait: Effect of different perturbation distances on slip recovery" [J.
Biomech. 49/2 (Jan. 2016) 149-154].
PMID- 27503662
TI - Pharmacokinetics of a Once-Daily Dose of Tacrolimus Early After Liver
Transplantation: With Special Reference to CYP3A5 and ABCB1 Single Nucleotide
Polymorphisms.
AB - BACKGROUND The aim of the present study was to investigate the pharmacokinetics
of the once-daily tacrolimus formulation (QD form) in relation to polymorphisms
of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene
and recipient adenosine triphosphate-binding cassette sub-family B member 1
(ABCB1) gene. MATERIAL AND METHODS A total of 80 consecutive living-donor liver
transplant (LDLT) recipients were started on the QD form of tacrolimus (day 1),
and 60 patients were completely followed for 7 days early after liver
transplantation in order to evaluate the pharmacokinetics. RESULTS The
concentration/dose (C/D) ratio in recipients with the donor CYP3A5 *1 allele was
significantly lower throughout the observation period compared with those with
the CYP3A5 genotype *3/*3 (p<0.001), while no effect of single-nucleotide
polymorphisms (SNPs) of ABCB1 was observed. The administered doses required to
achieve the target trough level were significantly higher on day 7 than on day 1
among all groups, regardless of the differences in the SNPs, especially among
those with donor CYP3A5 *1 allele. The tacrolimus concentration was kept within
the targeted level all through the study regardless of SNPs. CONCLUSIONS The
donor CYP3A5 *1 allele correlated with the lower C/D ratio after administration
of the QD form, and higher doses of QD-form tacrolimus and careful monitoring for
the trough level should be considered, especially in recipients with the donor
CYP3A5 *1 allele.
PMID- 27503665
TI - Dr Barnett Rosenberg - a Personal Perspective.
PMID- 27503664
TI - Ballistocardiogram: Mechanism and Potential for Unobtrusive Cardiovascular Health
Monitoring.
AB - For more than a century, it has been known that the body recoils each time the
heart ejects blood into the arteries. These subtle cardiogenic body movements
have been measured with increasingly convenient ballistocardiography (BCG)
instruments over the years. A typical BCG measurement shows several waves, most
notably the "I", "J", and "K" waves. However, the mechanism for the genesis of
these waves has remained elusive. We formulated a simple mathematical model of
the BCG waveform. We showed that the model could predict the BCG waves as well as
physiologic timings and amplitudes of the major waves. The validated model
reveals that the principal mechanism for the genesis of the BCG waves is blood
pressure gradients in the ascending and descending aorta. This new mechanistic
insight may be exploited to allow BCG to realize its potential for unobtrusive
monitoring and diagnosis of cardiovascular health and disease.
PMID- 27503666
TI - Photosensitizer cross-linked nano-micelle platform for multimodal imaging guided
synergistic photothermal/photodynamic therapy.
AB - The multifunctional nano-micelle platform holds great promise to enhance the
accuracy and efficiency of cancer diagnosis and therapy. In this work, an
amphiphilic poly[(poly(ethylene glycol) methyl ether methacrylate)-co-(3
aminopropyl methacrylate)]-block-poly(methyl methacrylate) (P(PEGMA-co-APMA)-b
PMMA) block copolymer was synthesized by successive RAFT polymerizations and
subsequent chemical modification. Then the multifunctional micelles with high
solubility in physiological environments were developed by a self-assembly and
crosslinking processes. The photosensitizer segment, 5,10,15,20-tetrakis (4
carboxyphenyl) porphyrin (TCPP), serves as a tetra-functional cross-linker,
photodynamic agent, fluorescence indicator, as well as magnetic resonance (MR)
contrast agent after labelling with manganese ions (Mn(2+)), while IR825
simultaneously locating in the interior of the fabricated micelles contributed to
the photoacoustic (PA) imaging ability and the photothermal effect. The prepared
nanoparticles show great stability in a physiological environment with uniform
morphology and diameters of around 80 nm as disclosed by stability investigation,
TEM and DLS analysis. IR825@P(PEGMA-co-APMA)-b-PMMA@TCPP/Mn nanoparticles
displayed high in vivo tumor uptake with a long blood circulation half-life
(~3.64 h) by the EPR effect after intravenous (i.v.) injection, as revealed by
fluorescence, MR and PA imaging models. In vivo anti-tumor effects were achieved
via a combined photothermal and photodynamic therapy without noticeable dark
toxicity, and this strategy was able to induce a remarkably improved synergistic
therapeutic effect to both superficial and deep regions of tumors under mild
conditions compared with either single photothermal or photodynamic mechanisms.
PMID- 27503667
TI - Nano-Structured Materials as Separation Media.
PMID- 27503669
TI - Errata.
PMID- 27503670
TI - Elucidating the Stereochemistry of Enzymatic Benzylsuccinate Synthesis with
Chirally Labeled Toluene.
AB - Benzylsuccinate synthase is a glycyl radical enzyme that initiates anaerobic
toluene metabolism by adding fumarate to the methyl group of toluene to yield (R)
benzylsuccinate. To investigate whether the reaction occurs with retention or
inversion of configuration at the methyl group of toluene, we synthesized both
enantiomers of chiral toluene with all three H isotopes in their methyl groups.
The chiral toluenes were converted into benzylsuccinates preferentially
containing (2) H and (3) H at their benzylic C atoms, owing to a kinetic isotope
effect favoring hydrogen abstraction from the methyl groups. The configuration of
the products was analyzed by enzymatic CoA-thioester synthesis and stereospecific
oxidation using enzymes involved in benzylsuccinate degradation. Assessment of
the configurations of the benzylsuccinate isomers based on loss or retention of
tritium showed that inversion of configuration at the methyl group occurs when
the chiral toluenes react with fumarate.
PMID- 27503671
TI - Differential effect of hypoxia on early endothelial-mesenchymal transition
response to transforming growth beta isoforms 1 and 2.
AB - Angiogenesis is essential for mammalian development and tissue homeostasis, and
is involved in several pathological processes, including tumor growth and
dissemination. Many factors within the tissue microenvironment are known to
modulate angiogenesis, including cytokines, such as transforming growth factor
beta (TGFbeta), and oxygen level. TGFbeta exists in three different isoforms (1,
2 and 3), all of which (albeit in different contexts) might mediate angiogenesis
and are able to induce endothelial-mesenchymal transition (EndoMT), a process
involved in heart development, pathologic fibrosis and, as recently reported, in
angiogenesis. Low oxygen level, referred to as hypoxia, has been independently
shown to induce angiogenesis, modulate TGFbeta signalling and promote EndoMT.
However, how these phenomena might be interconnected to drive angiogenesis is
rather unexplored. To begin addressing the potential contribution of TGFbeta
induced EndoMT to angiogenesis, and to explore how microenvironmental hypoxia
might influence these processes, we investigated the effect of TGFbeta isoforms 1
and 2 on early EndoMT response in cultured adult endothelium under standard (21
%) and hypoxic (1 %) culture conditions. Our data indicates that EndoMT-like
changes, such as an increase in expression and nuclear translocation of Snail,
Slug and Zeb1, and reduction of VE-cadherin expression, occur in response to
TGFbeta1 and/or TGFbeta2 as early as 6h after stimulation and might be enhanced
by hypoxia in an isoform-specific manner. Further, hypoxia enhances canonical
TGFbeta signalling, and appears to be a key determinant of Snail's differential
involvement in endothelial cell responses to TGFbeta1 versus TGFbeta2.
PMID- 27503672
TI - Providing innovative solutions in a single pill: Servier's portfolio in
hypertension.
AB - Jean-Jacques Mourad & Jean-Christophe Guillerm speak to Henry Ireland, Drug
Evaluation Editor: Jean-Jacques Mourad talks about his vision of the current
landscape and unmet medical needs in the field of hypertension. Jean-Christophe
Guillerm describes the family of antihypertensive treatments from Servier, which
were designed to address the current challenges in the management of hypertension
by providing an adapted solution to doctors and to the specific needs of each
patient. Jean-Jacques Mourad currently works as Professor of Medicine and is the
Head of the Hypertension Unit at the Hopital Avicenne in Bobigny, France. He
completed his academic degrees at the Pierre and Marie Curie University, Paris VI
in the field of internal and vascular medicine in 1996, and in the area of
cardiovascular medicine and pharmacology in 2001. He is the past president of the
French League Against Hypertension (since 2012), and the former General Secretary
of the French Microcirculation Society. He is the actual Scientific Secretary of
the French Society of Hypertension. He is also a member of the administrative
council of the College Francais de Pathologie Vasculaire. His research focuses on
the epidemiology of hypertension, arterial structure and function, determinants
of adherence to chronic treatment and the effects of antihypertensive agents. He
was involved in several studies and surveys. He is a co-author of more than 130
publications and of 900 communications presented at national and international
meetings. Jean-Christophe Guillerm, joined the pharmaceutical industry 17 years
ago. He is currently the Head of the Cardiovascular Division for Servier, in
charge of both cardiology and hypertension's medical strategy at a global level.
Prior to this, he was in charge of the diabetes and internal medicine franchise
at a global level. He also has experience in French commercial operations.
PMID- 27503673
TI - The Nutrition Society journals: vive la difference!
PMID- 27503674
TI - Nutrition information and front-of-pack labelling: issues in effectiveness.
PMID- 27503675
TI - How to talk about protein-level false discovery rates in shotgun proteomics.
AB - A frequently sought output from a shotgun proteomics experiment is a list of
proteins that we believe to have been present in the analyzed sample before
proteolytic digestion. The standard technique to control for errors in such lists
is to enforce a preset threshold for the false discovery rate (FDR). Many
consider protein-level FDRs a difficult and vague concept, as the measurement
entities, spectra, are manifestations of peptides and not proteins. Here, we
argue that this confusion is unnecessary and provide a framework on how to think
about protein-level FDRs, starting from its basic principle: the null hypothesis.
Specifically, we point out that two competing null hypotheses are used
concurrently in today's protein inference methods, which has gone unnoticed by
many. Using simulations of a shotgun proteomics experiment, we show how confusing
one null hypothesis for the other can lead to serious discrepancies in the FDR.
Furthermore, we demonstrate how the same simulations can be used to verify FDR
estimates of protein inference methods. In particular, we show that, for a simple
protein inference method, decoy models can be used to accurately estimate protein
level FDRs for both competing null hypotheses.
PMID- 27503676
TI - Arginine (Di)methylated Human Leukocyte Antigen Class I Peptides Are Favorably
Presented by HLA-B*07.
AB - Alterations in protein post-translational modification (PTM) are recognized
hallmarks of diseases. These modifications potentially provide a unique source of
disease-related human leukocyte antigen (HLA) class I-presented peptides that can
elicit specific immune responses. While phosphorylated HLA peptides have already
received attention, arginine methylated HLA class I peptide presentation has not
been characterized in detail. In a human B-cell line we detected 149 HLA class I
peptides harboring mono- and/or dimethylated arginine residues by mass
spectrometry. A striking preference was observed in the presentation of arginine
(di)methylated peptides for HLA-B*07 molecules, likely because the binding motifs
of this allele resemble consensus sequences recognized by arginine methyl
transferases. Moreover, HLA-B*07-bound peptides preferentially harbored
dimethylated groups at the P3 position, thus consecutively to the proline anchor
residue. Such a proline-arginine sequence has been associated with the arginine
methyl-transferases CARM1 and PRMT5. Making use of the specific neutral losses in
fragmentation spectra, we found most of the peptides to be asymmetrically
dimethylated, most likely by CARM1. These data expand our knowledge of the
processing and presentation of arginine (di)methylated HLA class I peptides and
demonstrate that these types of modified peptides can be presented for
recognition by T-cells. HLA class I peptides with mono- and dimethylated arginine
residues may therefore offer a novel target for immunotherapy.
PMID- 27503677
TI - Synthesis and trypanocidal activity of novel benzimidazole derivatives.
AB - The present work reports the synthesis and biological activity of a series of 14
benzimidazole derivatives designed to act on the enzyme triosephosphate isomerase
of Trypanosoma cruzi (TcTIM). This enzyme is involved in the metabolism of
glucose, the only source of energy for the parasite. In this study, we found four
compounds that inhibit TcTIM moderately and lack inhibitory activity against
human TIM (HsTIM). In vitro studies against T. cruzi epimastigotes showed two
compounds that were more active than the reference drug nifurtimox, and these
presented a low cytotoxic effect in mouse macrophages (J744 cell line).
PMID- 27503678
TI - Ligand-based virtual screen for the discovery of novel M5 inhibitor chemotypes.
AB - This Letter describes a ligand-based virtual screening campaign utilizing SAR
data around the M5 NAMs, ML375 and VU6000181. Both QSAR and shape scores were
employed to virtually screen a 98,000-member compound library. Neither approach
alone proved productive, but a consensus score of the two models identified a
novel scaffold which proved to be a modestly selective, but weak inhibitor
(VU0549108) of the M5 mAChR (M5 IC50=6.2MUM, M1-4 IC50s>10MUM) based on an
unusual 8-((1,3,5-trimethyl-1H-pyrazol-4-yl)sulfonyl)-1-oxa-4-thia-8
azaspiro[4,5]decane scaffold. [(3)H]-NMS binding studies showed that VU0549108
interacts with the orthosteric site (Ki of 2.7MUM), but it is not clear if this
is negative cooperativity or orthosteric binding. Interestingly, analogs
synthesized around VU0549108 proved weak, and SAR was very steep. However, this
campaign validated the approach and warranted further expansion to identify
additional novel chemotypes.
PMID- 27503679
TI - Synthesis and bioactivities of novel pyrazole oxime derivatives containing a
1,2,3-thiadiazole moiety.
AB - A series of new pyrazole oxime compounds bearing a 1,2,3-thiadiazole ring were
designed, synthesized, and evaluated for their insecticidal, acaricidal and
antitumor activities. Bioassays demonstrated that some title compounds displayed
satisfactory insecticidal and acaricidal properties. Especially, compounds 8d and
8h exhibited 90% insecticidal activities against Aphis craccivora at the
concentration of 100MUg/mL. Interestingly, some of the target compounds possessed
significant antitumor activities against four human cancer cell lines in vitro.
Among them, compounds 8e (IC50=7.19MUM), 8l (IC50=6.56MUM), 8m (IC50=8.12MUM),
and 8r (IC50=7.06MUM) had better inhibitory activities against HCT-116 cells than
the control 5-fluorouracil (IC50=29.50MUM). Additionally, compounds 8j, 8m, and
8r showed wonderful inhibitory activities against SGC-7901 cells with the IC50
values of 11.46, 9.41, and 8.64MUM, respectively, which were superior to that of
the control 5-fluorouracil.
PMID- 27503680
TI - Highly sensitive and selective detection of Al(III) ions in aqueous buffered
solution with fluorescent peptide-based sensor.
AB - A fluorescent sensor based on a tripeptide (SerGluGlu) with a dansyl fluorophore
detected selectively Al(III) among 16 metal ions in aqueous buffered solutions
without any organic cosolvent. The peptide-based sensor showed a highly sensitive
turn on response to aluminium ion with high binding affinity (1.84*10(4)M(-1)) in
aqueous buffered solutions. The detection limit (230nM, 5.98ppb) of the peptide
based sensor was much lower than the maximum allowable level (7.41MUM) of
aluminium ions in drinking water demanded by EPA. The binding mode of the peptide
sensor with aluminium ions was characterized using ESI mass spectrometry, NMR
titration, and pH titration experiments.
PMID- 27503681
TI - Design, synthesis and evaluation of the multidrug resistance-reversing activity
of pyridine acid esters of podophyllotoxin in human leukemia cells.
AB - Multidrug resistance (MDR) is the main cause for chemotherapeutic failure in
cancer treatment. To overcome MDR, a serious of pyridine acid esters of
podophyllotoxin was synthesized and their antiproliferation activities were
evaluated against two human chronic myeloid leukemia cell lines in vitro. Most of
them exhibited potent growth inhibition with IC50 values in the nanomolar range
as well as markedly reduced resistance factors. The most potent compound, Y8
exhibited an IC50 of 0.046+/-0.003MUM against resistance K562/ADR cells, showing
more significant than that of adriamycin and etoposide, respectively.
Furthermore, Y8 efficiently triggered cell cycle arrest at S phase and
simultaneously induced apoptosis in K562/ADR cells. Meanwhile, Y8 also regulated
the expression levels of cell cycle- and apoptosis-related proteins.
Additionally, Y8 stimulated the ERK1/2 signalling and reduced the expression of
Pgp protein. Finally, on the basis of results obtained using U0126, an ERK1/2
inhibitor, the ERK1/2 signalling pathway was proposed for the multidrug
resistance-reversing effect of Y8 in K562/ADR cells. Together, Y8 could be a
novel potential MDR reversal agent for the treatment of drug-resistant leukemia.
PMID- 27503682
TI - Synthesis of novel flavone derivatives possessing substituted benzamides and
their biological evaluation against human cancer cells.
AB - Baicalein is a well-known flavone derivative that possesses diverse biological
properties, such as anticancer, antioxidant and anti-inflammatory activities.
Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been
synthesized with the aim of enhancing its inherent biological activities. In the
present work, new flavones, possessing an N-aroylamine-substituent on the B-ring,
were synthesized to improve the cytotoxicity of baicalein and 5,6,7
trimethoxyflavone against human cancer cell lines. The majority of the flavones
synthesized exhibited greater cytotoxicity than baicalein and 5,6,7
trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n,
possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on
HepG2 (GI50=7.06MUM) and MCF-7 (GI50=7.67MUM) cells. In contrast, N-aroylamine
substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater
cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a
5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on
the cytotoxicity profile.
PMID- 27503683
TI - Non-canonical modulators of nuclear receptors.
AB - Like G protein-coupled receptors (GPCRs) and protein kinases, nuclear receptors
(NRs) are a rich source of pharmaceutical targets. Over 80 NR-targeting drugs
have been approved for 18 NRs. The focus of drug discovery in NRs has hitherto
been on identifying ligands that bind to the canonical ligand binding pockets of
the C-terminal ligand binding domains (LBDs). Due to the development of drug
resistance and selectivity concerns, there has been considerable interest in
exploring other, non-canonical ligand binding sites. Unfortunately, the potencies
of compounds binding at other sites have generally not been sufficient for
clinical development. However, the situation has changed dramatically over the
last 3years, as compounds with sufficient potency have been reported for several
NR targets. Here we review recent developments in this area from a medicinal
chemistry point of view in the hope of stimulating further interest in this area
of research.
PMID- 27503684
TI - Systematic chemical modifications of single stranded siRNAs significantly
improved CTNNB1 mRNA silencing.
AB - Single-stranded silencing RNAs (ss siRNA), while not as potent as duplex RNAs,
have the potential to become a novel platform technology in RNA interference
based gene silencing by virtue of their simplicity and plausibly favorable
characteristics in pharmacokinetics and biodistribution. Like other therapeutic
pharmaceutical agents, ss siRNA can be optimized to achieve higher potency
through a structure-activity based approach. Systematic chemical modification at
each position of a 21-mer oligonucleotide identified 2',5'-linked 3'
deoxythymidine (3dT) at position 1 and locked nucleic acids (LNAs) at the seed
region as key components to afford significant enhancement in knockdown activity
both in vitro and in vivo. Further optimization by additional chemical
modifications should enable ss siRNA as an alternative gene silencing modality.
PMID- 27503685
TI - Nature-inspired design of tetraindoles: Optimization of the core structure and
evaluation of structure-activity relationship.
AB - Building on the initial successful optimization of a novel series of
tetraindoles, a second generation of the compounds with changes in the core
phenyl ring was synthesized to improve anticancer properties. 17 new compounds
with different rigidity, planarity, symmetry and degree of conjugation of their
core structures to 5-hydroxyindole units were synthesized. All the compounds were
fully characterized and tested against breast cancer cell line (MDA-MB-231). The
results revealed that the core structure is required for activity and it should
be aromatic, rigid, planar, symmetrical and conjugated for optimal activity.
Compound 29, which has strong anticancer activity against various tumor-derived
cell lines, including Mahlavu (hepatocellular), SK-HEP-1 (hepatic), HCT116
(colon), MIA PaCa-2 (pancreatic), H441 (lung papillary), A549 (lung), H460 (non
small cell lung) and CL1-5 (lung carcinoma) with IC50 values ranging from 0.19 to
3.50MUM, was generated after series of successive optimizations. It was found to
induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in the
non-obese diabetic-severe combined immunodeficiency (NOD/SCID) mice bearing
xenografted MIA PaCa-2 human pancreatic cancer.
PMID- 27503686
TI - Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA
efflux pump inhibitors of Staphylococcus aureus.
AB - A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1
C18) with alpha-, beta- and gamma-amino acids were synthesized, characterized and
evaluated for their efflux pump inhibitory activity against ciprofloxacin
resistant Staphylococcus aureus. The amides were screened against NorA
overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium
bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and
reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold
reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay
proved these compounds as NorA inhibitors.
PMID- 27503687
TI - Metabolism of poplar salicinoids by the generalist herbivore Lymantria dispar
(Lepidoptera).
AB - The survival of insect herbivores on chemically defended plants may often depend
on their ability to metabolize these defense compounds. However, only little
knowledge is available on how insects actually process most plant defense
compounds. We investigated the metabolism of salicinoids, a major group of
phenolic glycosides in poplar and willow species, by a generalist herbivore, the
gypsy moth (Lymantria dispar). Seven salicinoid metabolites identified in gypsy
moth caterpillar feces were mostly conjugates with glucose, cysteine or glycine.
Two of the glucosides were phosphorylated, a feature not previously reported for
insect metabolites of plant defense compounds. The origins of these metabolites
were traced to specific moieties of three major poplar salicinoids ingested,
salicin, salicortin and tremulacin. Based on the observed metabolite patterns we
were able to deduce the initial steps of salicinoid breakdown in L. dispar guts,
which involves cleavage of ester bonds. The conjugated molecules were effectively
eliminated within 24 h after ingestion. Some of the initial breakdown products
(salicin and catechol) demonstrated negative effects on insect growth and
survival in bioassays on artificial diets. Gypsy moth caterpillars with prior
feeding experience on salicinoid-containing poplar foliage converted salicinoids
to the identified metabolites more efficiently than caterpillars pre-fed an
artificial diet. The majority of the metabolites we identified were also produced
by other common poplar-feeding insects. The conversion of plant defenses like
salicinoids to a variety of water-soluble sugar, phosphate and amino acid
conjugates and their subsequent excretion fits the general detoxification
strategy found in insect herbivores and other animals.
PMID- 27503688
TI - u1 -Opioid receptors in the dorsomedial and ventrolateral columns of the
periaqueductal grey matter are critical for the enhancement of post-ictal
antinociception.
AB - Generalised tonic and tonic-clonic seizures are followed by significant increase
in nociceptive thresholds in both laboratory animals and humans. The endogenous
opioid peptides play a role in antinociceptive signalling, and the periaqueductal
grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this
investigation was to evaluate the role of u1 -opioid receptors in the dorsomedial
(dm) and ventrolateral (vl) columns of PAG in post-ictal antinociception.
Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA-mediated Cl-
influx antagonist, was intraperitoneally (IP) administered to induce tonic-clonic
seizures in Wistar rats. The tail-flick test was used to measure the nociceptive
threshold. Microinjections of naltrexone (5.0 ug/0.2 uL), which is a non
selective opioid receptor antagonist, in both dmPAG and vlPAG decreased the tonic
clonic seizure-induced antinociception in seizing animals from 10 to 120 min
after seizures. Furthermore, microinjections of the u1 -opioid receptor-selective
antagonist naloxonazine (5.0 ug/0.2 uL) into the dmPAG decreased post-ictal
antinociception immediately after convulsive reactions and from 10 to 90 min
after seizures. However, vlPAG-pretreatment with naloxonazine at the same
concentration decreased the post-ictal antinociception 30 min after the onset of
tonic-clonic seizures and the nociceptive threshold returned to basal values 120
min after seizures. These findings indicate that u1 -opioid receptor-signalling
mechanisms in both dmPAG and vlPAG play a relevant role in the organisation of
post-ictal antinociception. In addition, u1 -opioid receptors in the dmPAG rather
than in vlPAG seem to be more critically recruited during the antinociception
induced by generalised tonic-clonic seizures.
PMID- 27503689
TI - Becoming business critical: Knowledge for Healthcare.
AB - Significant progress has been made in implementing Knowledge for Healthcare. This
editorial reports the central contribution of effective partnerships and the
involvement of librarians and knowledge specialists in this work. There are
compelling business priorities. Key elements of work-streams on demonstrating
impact, workforce development and streamlining are indicated, along with areas of
growing importance - knowledge management, embedded roles and health information
for the public and patients. Knowledge, and the skills to help people to use it,
are business critical.
PMID- 27503690
TI - Demonstrating the financial impact of clinical libraries: a systematic review.
AB - OBJECTIVE: The purpose of this review is to evaluate the tools used to measure
the financial value of libraries in a clinical setting. METHODS: Searches were
carried out on ten databases for the years 2003-2013, with a final search before
completion to identify any recent papers. RESULTS: Eleven papers met the final
inclusion criteria. There was no evidence of a single 'best practice', and many
metrics used to measure financial impact of clinical libraries were developed on
an ad hoc basis locally. The most common measures of financial impact were value
of time saved, value of resource collection against cost of alternative sources,
cost avoidance and revenue generated through assistance on grant submissions. Few
papers provided an insight into the longer term impact on the library service
resulting from submitting return on investment (ROI) or other financial impact
statements. CONCLUSIONS: There are limited examples of metrics which clinical
libraries can use to measure explicit financial impact. The methods highlighted
in this literature review are generally implicit in the measures used and lack
robustness. There is a need for future research to develop standardised,
validated tools that clinical libraries can use to demonstrate their financial
impact.
PMID- 27503691
TI - Empowering international nursing students to become effective library users.
AB - This article summarises the research conducted for a dissertation which addressed
the needs of students and academic staff of the Bachelor of Nursing International
programme at St. Angela's College, Ireland. Aoife Murray completed an MSc Econ
Information and Library Studies in 2015 from Aberystwyth University via distance
learning. She gained a distinction for her work and has co-written the article
with Hugh Preston, her dissertation supervisor. Aoife highlights the
recommendations she made as a result of her research and the programme put in
place to deliver those recommendations. She also reports on some early
evaluations of the new programme. AM.
PMID- 27503692
TI - International collaborations in learning and teaching: perspectives from a
visiting professorship.
AB - This article provides a reflection on the outcomes of an international
collaboration between health librarians and academics at York St John University
and Pacific University Oregon. In particular, it describes how a month-long
visiting professorship from an academic with a clinical librarian background at
the Faculty of Health and Life Sciences helped to develop and inform teaching
practice in the areas of information literacy and evidence-based health practice
on health programmes at Pacific University. Perspectives are offered from both
institutions on the rich exchange of knowledge and practice that took place
during the visit and the ongoing impact it has had on teaching practices. H. S.
PMID- 27503693
TI - Hormonal therapy for endometriosis: from molecular research to bedside.
AB - Endometriotic lesions are associated with hormonal imbalance, including increased
estrogen synthesis, metabolism and progesterone resistance. These hormonal
changes cause increased proliferation, inflammation, pain and infertility.
Hormonal imbalances are targets for treatment. Therapeutic strategies and
innovations of hormonal drugs for endometriosis are increasing. Acting on
estrogen receptors are hormonal drugs decreasing systemic and local estrogen
synthesis (GnRH analogs, GnRH antagonists, Aromatase inhibitors) or estrogen
activity (selective estrogen receptor modulators). The progesterone resistance is
counteracted by progestins (Medroxyprogesterone acetate, Dienogest, Danazol,
Levonorgestrel) or by Selective progesterone receptor modulators, a class of
drugs under development. The future trend will be to define new drugs to use for
prolonged period of time and with poor side effects considering endometriosis a
chronic disease.
PMID- 27503694
TI - Diagnosing Infection in Patients Undergoing Conversion of Prior Internal Fixation
to Total Hip Arthroplasty.
AB - BACKGROUND: Criteria for diagnosis of infected internal fixation implants at the
time of conversion to total hip arthroplasty (THA) are not clear. The purpose of
this study is to identify risk factors for infection in patients undergoing
conversion to THA. METHODS: We retrospectively reviewed patients at a single
institution who underwent conversion to THA from 2009 to 2014. Patients were
diagnosed with infection preoperatively using Musculoskeletal Infection Society
criteria or postoperatively if they were found to have positive cultures
intraoperatively at the time of conversion surgery. Medical comorbidities and
preoperative inflammatory markers were compared between infected and noninfected
groups. Univariate and multivariate logistic regression analysis were performed
to identify independent risk factors for infection. Receiver operating
characteristic curves were generated to determine test performance of erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP). A post hoc power analysis
was performed. RESULTS: Thirty-three patients were included in the study. Six
patients (18%) were diagnosed with infection. We found no association between
comorbidities and infection in this cohort. The mean ESR and CRP were higher in
infected (ESR = 41.6 mm/h, CRP = 2.0 mg/dL) vs noninfected (ESR = 19.3 mm/h, CRP
= 1.3 mg/dL) groups (both P < .01). ESR >30 mm/h (odds ratio 28.8, 95% confidence
interval 2.6-315.4, P = .001) and CRP >1.0 mg/dL (odds ratio 11.5, 95% confidence
interval 1.6-85.2, P = .01) were strongly associated with infection. Receiver
operating characteristic curves for ESR (area under the curve [AUC] = 0.89) and
CRP (AUC = 0.89) demonstrated good fit. CONCLUSION: We report a high incidence of
infection in patients who underwent conversion to THA. Preoperative ESR and CRP
are effective screening tools though occult infections may still be missed.
Patients with borderline or elevated inflammatory markers should raise strong
suspicion for infection.
PMID- 27503695
TI - Preoperative Glycemic Control on Total Joint Arthroplasty Patient-Perceived
Outcomes and Hospital Costs.
AB - BACKGROUND: The purpose of this study was to determine the influence of
preoperative glycemic control in diabetic patients undergoing a primary total hip
or knee arthroplasty. We wanted to study patient-perceived outcomes in the medium
term, the length of stay, hospital costs, and rate of short-term postoperative
complications. METHODS: One hundred twenty consecutive primary total joint
arthroplasties (TJAs) performed in type 2 diabetic patients were stratified into
2 groups representing optimal and suboptimal preoperative glycemic control, based
on serum levels of glycated hemoglobin (HbA1c), and those groups compared.
RESULTS: The mean follow-up time was 5.9 years (range, 2.1-10.7 years). Both
groups demonstrated improvement in all patient-perceived outcome measures after
TJA, with no significant difference detected in any change of a measure between
the groups. No significant difference was detected in the length of stay,
hospital costs, or rate of short-term postoperative complications between the
groups. CONCLUSION: Preoperative glycemic control in type 2 diabetic patients
undergoing TJA did not affect patient-perceived outcomes in the medium term.
Optimal vs suboptimal glycemic control in these patients also had no effect on
the length of stay, hospital costs, or rate of short-term postoperative
complications.
PMID- 27503696
TI - Infection Is Not a Risk Factor for Perioperative and Postoperative Blood Loss and
Transfusion in Revision Total Hip Arthroplasty.
AB - BACKGROUND: Septic hip revisions are associated with greater complications and
higher costs than aseptic revisions. It is unclear whether blood loss and
transfusion requirements are different in septic and aseptic revisions. We
hypothesized that the blood loss and transfusion are dependent on the complexity
of the revision surgery and patient's general health rather than the presence of
infection. METHODS: We retrospectively reviewed 626 revision total hip
arthroplasties in 547 patients between 2009 and 2013. All the procedures were
classified as septic (n = 120) or aseptic (n = 506) based on the Musculoskeletal
Infection Society criteria for periprosthetic joint infection. Independent risk
factors for transfusion and blood loss were analyzed using a multiple regression
analysis. RESULTS: The transfusion rate was higher in septic revisions (septic =
108/120 [90%], aseptic = 370/506 [73%]; P < .001), so was the average amount of
blood loss (septic = 2533 +/- 161 mL, aseptic = 1974 +/- 68 mL; P < .001). After
adjusting for potential confounders, infection was not an independent risk factor
for transfusion (P = .176) or blood loss (P = .437). Increasing age (P = .004),
higher American Society of Anesthesiologists score (P = .047), lower preoperative
hemoglobin (P < .001), cell saver use (P < .001), and complex revision surgery (P
< .001) were independently associated with greater risk of transfusion.
CONCLUSIONS: Although blood loss and transfusion rates were higher in septic
revisions, the presence of infection alone did not increase the risk of
transfusion or blood loss. Blood management strategies in revision total hip
arthroplasties should be guided by the type of surgery planned and patient's
preoperative health rather than the presence of infection.
PMID- 27503697
TI - Comparison of Midterm Outcomes of Minimally Invasive Computer-Assisted vs
Minimally Invasive Jig-Based Total Knee Arthroplasty.
AB - BACKGROUND: Minimally invasive surgery (MIS) has perceived advantages in the
early postoperative stage for total knee arthroplasty (TKA). It is not clear
whether the improved radiographic alignment achieved by computer-assisted
navigation surgery (CAS) improves midterm clinical outcomes. The aim of this
study was to compare patient outcomes of MIS TKA performed with and without CAS
after a minimum follow-up of 7 years. METHODS: Between 2007 and 2009, 50 patients
underwent CAS and MIS TKA, and 50 patients underwent jig-based MIS TKA in this
prospective study. Ninety-six patients were evaluated after a mean follow-up of
7.7 years, and clinical and radiological evaluations were performed. RESULTS:
Midterm results demonstrated that the Knee Society knee score, function score,
and range of motion were comparable in the 2 groups. The percentage of patients
with the mechanical axis within +/-3 degrees of neutral was significantly higher
in the CAS group than in the jig-based group (94% vs 79%, respectively; P =
.038). No knees had loosening after TKA. However, 1 patient in the CAS group
demonstrated late infection 4 years postoperatively. CONCLUSION: CAS did not
improve midterm outcomes after MIS TKA compared with jig-based surgery, although
CAS reduced outliers in coronal alignment.
PMID- 27503698
TI - Interactions between mitochondrial and nuclear DNA in mammalian cells are non
random.
AB - Chromosome Conformation Capture techniques regularly detect physical interactions
between mitochondrial and nuclear DNA (i.e. mito-nDNA interactions) in mammalian
cells. We have evaluated mito-nDNA interactions captured by HiC and Circular
Chromosome Conformation Capture (4C). We show that these mito-nDNA interactions
are statistically significant and shared between biological and technical
replicates. The most frequent interactions occur with repetitive DNA sequences,
including centromeres in human cell lines and the 18S rDNA in mouse cortical
astrocytes. Our results demonstrate a degree of selective regulation in the
identity of the interacting mitochondrial partners confirming that mito-nDNA
interactions in mammalian cells are not random.
PMID- 27503699
TI - Early changes of brain connectivity in primary open angle glaucoma.
AB - Our aim was to assess in primary open angle glaucoma (POAG), a major cause of
irreversible blindness worldwide, whether diffuse brain changes recently shown in
advanced stage can be detected since the early stage. We used multimodal magnetic
resonance imaging (MRI) in 57 patients with the three POAG stages and in 29 age
matched normal controls (NC). Voxelwise statistics was performed with
nonparametric permutation testing. Compared with NC, disrupted anatomical
connectivity (AC) was found in the whole POAG group along the visual pathway and
in nonvisual white matter tracts (P < 0.001). Moreover, POAG patients showed
decreased functional connectivity (FC) in the visual (P = 0.004) and working
memory (P < 0.001) networks whereas an increase occurred in the default mode (P =
0.002) and subcortical (P < 0.001) networks. Altered AC and FC were already
present in early POAG (n = 14) in both visual and nonvisual systems (P <= 0.01).
Only severe POAG (n = 30) showed gray matter atrophy and this mapped on visual
cortex (P < 0.001) and hippocampus (P < 0.001). Increasing POAG stage was
associated with worsening AC in both visual and nonvisual pathway (P < 0.001),
progressive atrophy in the hippocampus and frontal cortex (P < 0.003). Most of
the structural and functional alterations within and outside the visual system
showed correlation (P < 0.001 to 0.02) with computerized visual field and retinal
nerve fiber layer thickness. In conclusion, the complex pathogenesis of POAG
includes widespread damage of AC and altered FC within and beyond the visual
system since the early disease stage. The association of brain MRI changes with
measures of visual severity emphasizes the clinical relevance of our findings.
Hum Brain Mapp 37:4581-4596, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27503700
TI - Quantitative analyses of cellularity and proliferative activity reveals the
dynamics of the central canal lining during postnatal development of the rat.
AB - According to previous opinion, the derivation of neurons and glia from the
central canal (CC) lining of the spinal cord in rodents should occur in the
embryonic period. Reports of the mitotic activity observed in the lining during
postnatal development have often been contradictory, and proliferation was
ascribed to the generation of ependymocytes, which are necessary for the
elongation of CC walls. Our study quantifies the intensity of proliferation and
determines the cellularity of the CC lining in reference to lumbar spinal segment
L4 during the postnatal development of rats. The presence of dividing cells peaks
in the CC lining on postnatal day 8 (P8), with division occurring in 19.2% +/-
3.2% of cells. In adult rats, 3.6% +/- 0.9% of cells still proliferate, whereas,
in mice, 10.3% +/- 2.3% of cells at P8 and only 0.6% +/- 0.2% of cells in the CC
lining in adulthood are proliferating. In the rat, the length of the cell cycle
increases from 100.3 +/- 35.7 hours at P1 to 401.4 +/- 80.6 hours at P43, with a
sudden extension between P15 and P22. Despite the intensive proliferation, the
total cellularity of the CC lining at the L4 spinal segment significantly
descended in from P8 to P15. According to our calculations, the estimated
cellularity was significantly higher compared with the measured cellularity of
the CC lining at P15. Our results indicate that CC lining serves as a source of
cells beyond ependymal cells during the first postnatal weeks of the rat. J.
Comp. Neurol. 525:693-707, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27503701
TI - Effect of assisted hatching on pregnancy outcomes: a systematic review and meta
analysis of randomized controlled trials.
AB - Emerging evidence suggests that assisted hatching (AH) techniques may improve
clinical pregnancy rates, particularly in poor prognosis patients; however, there
still remains considerable uncertainty. We conducted a meta-analysis to verify
the effect of AH on pregnancy outcomes. We searched for related studies published
in PubMed, Web of Science, and Cochrane library databases from start dates to
October 10, 2015. Totally, 36 randomized controlled trials with 6459 participants
were included. Summary odds ratios (ORs) with 95% confidence intervals (CIs) for
whether by AH or not were estimated. We found a significant increase in clinical
pregnancy (OR = 1.16, 95% CI = 1.00-1.36, I(2) = 48.3%) and multiple pregnancy
rates (OR = 1.50, 95% CI = 1.11-2.01, I(2) = 44.0%) with AH when compared to the
control. Numerous subgroup analyses stratified by hatching method, conception
mode, extent of AH, embryos transfer status, and previous failure history were
also carried out. Interestingly, significant results of clinical pregnancy as
well as multiple pregnancy rates were observed among women who received
intracytoplasmic sperm injection, and who received AH which the zona were
completely removed. In summary, this meta-analysis supports that AH was
associated with an increased chance of achieving clinical pregnancy and multiple
pregnancy. Whether AH significantly changes live birth and miscarriage rates
needs further investigations.
PMID- 27503702
TI - Learning from facial expressions in individuals with Williams syndrome.
AB - BACKGROUND: Despite high levels of social engagement, the social competence of
individuals with Williams syndrome (WS) is frequently compromised. This
descriptive study explores the ability of young people with WS to learn from
facial expressions when provided as a source of feedback for their actions.
METHOD: Using a novel task, the ability to interpret facial expressions and adapt
behaviour after receiving feedback in the form of happy or angry faces was
assessed in 12 participants with WS aged between 10 and 28 years and with a mean
nonverbal mental age of 6.5 years, and in typically developing (TD) children aged
between 4 and 7 years. RESULTS: Individuals with WS were able to use facial
expressions as feedback in a manner commensurate with their mental age, only when
other cognitive demands were low. Their performance profile differed from that of
the TD children matched for mental age and from the performance profile of 4 year
olds. CONCLUSIONS: Possible explanations for the unique performance profile
observed in the participants with WS are discussed. The results highlight the
need to examine social competencies in the context of the cognitive demands
characteristic of social environments.
PMID- 27503703
TI - Prevalence of autism and attention-deficit-hyperactivity disorder in Down
syndrome: a population-based study.
AB - AIM: To investigate the prevalence of autism spectrum disorder (ASD) and
attention-deficit-hyperactivity disorder (ADHD) in a population-based group of
children and adolescents with Down syndrome, and to relate the findings to level
of intellectual disability and to medical conditions. METHOD: From a population
based cohort of 60 children and adolescents with Down syndrome, 41 individuals
(29 males, 12 females; mean age 11y, age range 5-17y) for whom parents gave
consent for participation were clinically assessed with regard to ASD and ADHD.
The main instruments used were the Autism Diagnostic Interview-Revised, Autism
Diagnostic Observation Schedule, Swanson, Nolan, and Pelham-IV Rating Scale, and
the Adaptive Behavior Assessment System-II. RESULTS: High rates of ASD and ADHD
were found: 17 (42%) and 14 (34%) of the 41 children met DSM criteria for ASD and
ADHD respectively. INTERPRETATION: Children with Down syndrome and coexisting
neurodevelopmental/neuropsychiatric disorders in addition to intellectual
disability and medical disorders constitute a severely disabled group. Based on
the results, we suggest that screening is implemented for both ASD and ADHD, at
the age of 3 to 5 years and early school years respectively, to make adequate
interventions possible.
PMID- 27503704
TI - Molecular insights of organochlorine biocide-induced toxicity in zebrafish: Whole
adult-organism toxicogenomics, targeted gene expression and histological
analyses.
PMID- 27503705
TI - ?
AB - The identification of individual eukaryotic and prokaryotic cells is the backbone
of clinical pathology and provides crucial information about the genesis and
progression of a disease. While most commonly fluorescent-label based methods are
applied, label-free methods, such as Raman spectroscopy, are elegant
alternatives. A major disadvantage of Raman spectroscopy is the low signal yield
resulting in long acquisition times, making it impractical for high-throughput
clinical analysis. As a rule, Raman-based cell identification relies on high
resolution Raman spectra. This comes at a cost of detected Raman photons. In this
letter we show that while the proper biochemical characterization of cells
requires high-resolution Raman spectra, the proper classification of cells does
not. By varying the slit-width between 50 um and 500 um it is possible to show
that detected Raman signal from eukaryotic cells increased up to seven-fold.
Raman-based cell classification was performed on three cancer cell lines: Jurkat,
MiaPaca2, and Capan1, at three different resolutions 8 cm-1 , 24 cm-1 , and 48 cm
1 . Moreover, we have simulated the resolution decrease due to low-diffraction
gratings by binning neighboring pixels together. In both cases the cells were
well classifiable using support vectors machine (SVM). For anyone working in the
field of Raman spectroscopy this picture of Sir C.V. Raman is recognizable, even
with reduced spatial resolution. Raman spectra of eukaryotic cells can also be
recognized even with six fold reduced spectral resolution.
PMID- 27503706
TI - NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo.
AB - The replacement of injured neurons by the selective stimulation of neural stem
cells in situ represents a potential therapeutic strategy for the treatment of
neurodegenerative diseases. The peptide NFL-TBS.40-63 showed specific
interactions towards neural stem cells of the subventricular zone. The aim of our
work was to produce a NFL-based drug delivery system able to target neural stem
cells through the selective affinity between the peptide and these cells. NFL
TBS.40-63 (NFL) was adsorbed on lipid nanocapsules (LNC) whom targeting
efficiency was evaluated on neural stem cells from the subventricular zone
(brain) and from the central canal (spinal cord). NFL-LNC were incubated with
primary neural stem cells in vitro or injected in vivo in adult rat brain (right
lateral ventricle) or spinal cord (T10). NFL-LNC interactions with neural stem
cells were different depending on the origin of the cells. NFL-LNC showed a
preferential uptake by neural stem cells from the brain, while they did not
interact with neural stem cells from the spinal cord. The results obtained in
vivo correlate with the results observed in vitro, demonstrating that NFL-LNC
represent a promising therapeutic strategy to selectively deliver bioactive
molecules to brain neural stem cells.
PMID- 27503708
TI - Mode-locking via dissipative Faraday instability.
AB - Emergence of coherent structures and patterns at the nonlinear stage of
modulation instability of a uniform state is an inherent feature of many
biological, physical and engineering systems. There are several well-studied
classical modulation instabilities, such as Benjamin-Feir, Turing and Faraday
instability, which play a critical role in the self-organization of energy and
matter in non-equilibrium physical, chemical and biological systems. Here we
experimentally demonstrate the dissipative Faraday instability induced by
spatially periodic zig-zag modulation of a dissipative parameter of the system
spectrally dependent losses-achieving generation of temporal patterns and high
harmonic mode-locking in a fibre laser. We demonstrate features of this
instability that distinguish it from both the Benjamin-Feir and the purely
dispersive Faraday instability. Our results open the possibilities for new
designs of mode-locked lasers and can be extended to other fields of physics and
engineering.
PMID- 27503707
TI - Ultrasound-guided therapeutic modulation of hepatocellular carcinoma using
complementary microRNAs.
AB - Treatment options for patients with hepatocellular carcinoma (HCC) are limited,
in particular in advanced and drug resistant HCC. MicroRNAs (miRNA) are non
coding small RNAs that are emerging as novel drugs for the treatment of cancer.
The aim of this study was to assess treatment effects of two complementary miRNAs
(sense miRNA-122, and antisense antimiR-21) encapsulated in biodegradable poly
(lactic-co-glycolic acid) nanoparticles (PLGA-NP), administered by an ultrasound
guided and microbubble-enhanced delivery approach in doxorubicin-resistant and
non-resistant human HCC xenografts. Proliferation and invasiveness of human HCC
cells after miRNA-122/antimiR-21 and doxorubicin treatment were assessed in
vitro. Confocal microscopy and qRT-PCR were used to visualize and quantitate
successful intracellular miRNA-loaded PLGA-NP delivery. Up and down-regulation of
miRNA downstream targets and multidrug resistance proteins and extent of
apoptosis were assessed in vivo in treated human HCC xenografts in mice. Compared
to single miRNA therapy, combination therapy with the two complementary miRNAs
resulted in significantly (P<0.05) stronger decrease in cell proliferation,
invasion, and migration of HCC cells as well as higher resensitization to
doxorubicin. Ultrasound-guided delivery significantly increased in vivo miRNA
loaded PLGA-NP delivery in human HCC xenografts compared to control conditions by
5-9 fold (P<0.001). miRNA-loaded PLGA-NP were internalized in HCC cells and anti
apoptotic proteins were down regulated with apoptosis in ~27% of the tumor volume
of doxorubicin-resistant human HCC after a single treatment with complementary
miRNAs and doxorubicin. Thus, ultrasound-guided delivery of complementary miRNAs
is highly efficient in the treatment of doxorubicin- resistant and non-resistant
HCC. Further development of this new treatment approach could aid in better
treatment of patients with HCC.
PMID- 27503709
TI - Pseudomonas turukhanskensis sp. nov., isolated from oil-contaminated soils.
AB - A bacterial strain named IB1.1T was isolated in a screening of hydrocarbon
degrading bacteria from oil-contaminated soils on the territory of the Turukhansk
District of Krasnoyarsk Krai, East Siberia, Russia. The 16S rRNA gene sequence
had 98.7 % identity with respect to the closest phylogenetic relative,
Pseudomonas granadensis F-278,770T, and the next most closely related species
with 98.6 % similarity was Pseudomonaspunonensis, suggesting that IB1.1T should
be classified within the genus Pseudomonas. The analysis of housekeeping genes
rpoB, rpoD and gyrB showed similarities lower than 90 % in all cases with respect
to the closest relatives, confirming its phylogenetic affiliation. The strain
showed a polar flagellum. The respiratory quinone was Q9. The major fatty acids
were 16 : 1omega7c/16 : 1omega6c (summed feature 3), 18 : 1omega7c and 16 : 0.
The strain was oxidase- and catalase-positive, but the arginine dihydrolase
system was not present. Nitrate reduction, urease and beta-galactosidase
production, and aesculin hydrolysis were negative. The temperature range for
growth was 4-34 degrees C, and the strain could grow at pH 11. The DNA G+C
content was 58.5 mol%. DNA-DNA hybridization results showed values of less than
30 % relatedness with respect to the type strains of the eight most closely
related species. Therefore, the dataset of genotypic, phenotypic and
chemotaxonomic data support the classification of strain IB1.1T into a novel
species of the genus Pseudomonas, for which the name Pseudomonasturukhanskensis
sp. nov. is proposed. The type strain is IB1.1T (=VKM B-2935T=CECT 9091T).
PMID- 27503710
TI - Dietary alpha-ketoglutarate increases cold tolerance in Drosophila melanogaster
and enhances protein pool and antioxidant defense in sex-specific manner.
AB - Alpha-ketoglutarate (AKG) is an important intermediate in Krebs cycle which
bridges the metabolism of amino acids and carbohydrates. Its effects as a dietary
supplement on cold tolerance were studied in Drosophila melanogaster Canton S.
Two-day-old adult flies fed at larval and adult stages with AKG at moderate
concentrations (5-10mM) recovered faster from chill coma (0 degrees C for 15min
or 3h) than control ones. The beneficial effect of AKG on chill coma recovery was
not found at its higher concentrations, which suggests hormetic like action of
this keto acid. Time of 50% observed mortality after 2h recovery from continuous
cold exposure (-1 degrees C for 3-31h) (LTi50) was higher for flies reared on
10mM AKG compared with control ones, showing that the diet with AKG enhanced
insect cold tolerance. In parallel with enhancement of cold tolerance, dietary
AKG improved fly locomotor activity. Metabolic effects of AKG differed partly in
males and females. In males fed on AKG, there were no differences in total
protein and free amino acid levels, but the total antioxidant capacity, catalase
activity and low molecular mass thiol content were higher than in control
animals. In females, dietary AKG promoted higher total antioxidant capacity and
higher levels of proteins, total amino acids, proline and low molecular mass
thiols. The levels of lipid peroxides were lower in both fly sexes reared on AKG
as compared with control ones. We conclude that both enhancement of antioxidant
system capacity and synthesis of amino acids can be important for AKG-promoted
cold tolerance in D. melanogaster. The involvement of AKG in metabolic pathways
of Drosophila males and females is discussed.
PMID- 27503711
TI - Local weather conditions have complex effects on the growth of blue tit
nestlings.
AB - Adverse weather conditions are expected to result in impaired nestling
development in birds, but empirical studies have provided equivocal support for
such a relationship. This may be because the negative effects of adverse weather
conditions are masked by parental effects. Globally, ambient temperatures,
rainfall levels and wind speeds are all expected to increase in a changing
climate and so there is a need for a better understanding of the relationship
between weather conditions and nestling growth. Here, we describe a correlative
study that examined the relationships between local temperatures, rainfall levels
and wind speeds and the growth of individual blue tit (Cyanistes caeruleus)
nestlings in relation to their hatching order and sex. We found that changes in a
range of morphological characters were negatively related to both temperature and
wind speed, but positively related to rainfall. These patterns were further
influenced by the hatching order of the nestlings but not by nestling sex. This
suggests that the predicted changes in local weather conditions may have complex
effects on nestling growth, but that parents may be able to mitigate the adverse
effects via adaptive parental effects. We therefore conclude that local weather
conditions have complex effects on avian growth and the implications for patterns
of avian growth in a changing climate are discussed.
PMID- 27503712
TI - The use of thermal imaging to assess the effectiveness of ice massage and cold
water immersion as methods for supporting post-exercise recovery.
AB - Cold water immersion (CWI) and ice massage (IM) are commonly used treatments to
prevent the delay onset of muscle soreness (DOMS); however, little is known on
their relative benefits and effectiveness to lower tissue temperature. This study
was designed to evaluate the effectiveness of IM and CMI on tissue temperature
and potential benefit to preventing DOMS. The research encompassed 36 subjects
divided into three groups of twelve depending on the form of recovery: ice
massage (IM), cold-water immersion (CWI), or passive recovery (PAS). All the
participants were asked to jump as high as possible from a full squat for one
minute. Thermal imaging was conducted at rest, immediately following the
exercise, immediately after the trial, following the recovery treatment, and
after 30min of rest. Their pain levels were assessed using the Visual Analogue
Scale (VAS). After applying the selected method for supporting recovery, the LA
level decreased by 4.25mmol/L in the IM group, and by 4.96mmol/L in the CWI group
(IM vs. CWI p>0.05). The 2.75mmol/L decrease in lactate concentration in the PAS
group was significantly lower than in the other groups (IM vs. PAS p<0.05/ CWI
vs. PAS p<0.01). In both groups, Tsk after 30min was significantly lower
(DeltaTsk~0.5 degrees C) than at rest (p<0.05). In turn, Tsk in the PAS group
returned to the resting values (p>0.05). Seventy-two hours after the exercise, a
clear decrease in discomfort was observed in the IM and CWI groups compared to
the PAS group. The two applied treatments have proven to be effective both in
utilizing lactate and preventing DOMS. Depending on training requirements, we
recommend the use of IM when athletes experience localized muscle fatigue. One
the other hand, CWI is recommended in situations of global or generalized muscle
injury or fatigue.
PMID- 27503713
TI - Mitigation of heat stress-related complications by a yeast fermentate product.
AB - Heat stress results in a multitude of biological and physiological responses
which can become lethal if not properly managed. It has been shown that heat
stress causes significant adverse effects in both human and animals. Different
approaches have been proposed to mitigate the adverse effects caused by heat
stress, among which are special diet and probiotics. We characterized the effect
of the yeast fermentate EpiCor (EH) on the prevention of heat stress-related
complications in rats. We found that increasing the body temperature of animals
from 37.1+/-0.2 to 40.6+/-0.2 degrees C by exposure to heat (45 degrees C for
25min) resulted in significant morphological changes in the intestine. Villi
height and total mucosal thickness decreased in heat-stressed rats pre-treated
with PBS in comparison with control animals not exposed to the heat. Oral
treatment of rats with EH before heat stress prevented the traumatic effects of
heat on the intestine. Changes in intestinal morphology of heat-stressed rats,
pre-treated with PBS resulted in significant elevation of lipopolysaccharides
(LPS) level in the serum of these animals. Pre-treatment with EH was effective in
the prevention of LPS release into the bloodstream of heat-stressed rats. Our
study revealed that elevation of body temperature also resulted in a significant
increase of the concentration of vesicles released by erythrocytes in rats, pre
treated with PBS. This is an indication of a pathological impact of heat on the
erythrocyte structure. Treatment of rats with EH completely protected their
erythrocytes from this heat-induced pathology. Finally, exposure to heat stress
conditions resulted in a significant increase of white blood cells in rats. In
the group of animals pre-treated with EH before heat stress, the white blood cell
count remained the same as in non-heated controls. These results showed the
protective effect of the EH product in the prevention of complications, caused by
heat stress.
PMID- 27503714
TI - Hypothermal effects on survival, energy homeostasis and expression of energy
related genes of swimming crabs Portunus trituberculatus during air exposure.
AB - Previously, dry or semi-dry approach under the hypothermal condition is proved to
be an alternative method in transport of live swimming crabs Portunus
trituberculatus. However, we wondered whether this method can improve crab
survival when temperature is kept as cool as possible. In this study, we
hypothesized that there is a thermal threshold below which dry or semi-dry
approach (air exposure) could cause crab physiological disruption and therefore
aggravate their mortality. To test the above hypothesis, crabs (23 degrees C)
were exposed to air at temperatures ranging from 4 to 16 degrees C. Results
showed that crabs had a worse survival and vigor at temperatures below 12 degrees
C. Then we tested crab energy metabolism to explore the possible reason. It was
shown that total adenine nucleotide and adenylate energy charge in gills were
remarkably reduced by air exposure of below 12 degrees C. This increased the need
for crabs to re-balance energy metabolism, which was indicated by the
upregulation of AMPKalpha and HIF-1alpha. Meanwhile, there was a significant
increase of the expression of Na(+)/K(+)-ATPase, V-type ATPase and HSP90 at
temperatures below 12 degrees C, while all treatments shared a similar level of
hemocyanin, urate and lactate in hemolymph and expression of cytochrome c oxidase
and NADH-ubiquinone reductase in gills. These results implied that dry or semi
dry approach below 12 degrees C could exert detrimental effects on P.
trituberculatus, and perturbation of energy homeostasis, which is more related
with changes of energy-demanding physiological pathways, is a possible reason of
crab death and poor vigor.
PMID- 27503715
TI - 'Optimal thermal range' in ectotherms: Defining criteria for tests of the
temperature-size-rule.
AB - Thermal performance curves for population growth rate r (a measure of fitness)
were estimated over a wide range of temperature for three species: Coleps hirtus
(Protista), Lecane inermis (Rotifera) and Aeolosoma hemprichi (Oligochaeta). We
measured individual body size and examined if predictions for the temperature
size rule (TSR) were valid for different temperatures. All three organisms
investigated follow the TSR, but only over a specific range between minimal and
optimal temperatures, while maintenance at temperatures beyond this range showed
the opposite pattern in these taxa. We consider minimal and optimal temperatures
to be species-specific, and moreover delineate a physiological range outside of
which an ectotherm is constrained against displaying size plasticity in response
to temperature. This thermal range concept has important implications for general
size-temperature studies. Furthermore, the concept of 'operating thermal
conditions' may provide a new approach to (i) defining criteria required for
investigating and interpreting temperature effects, and (ii) providing a novel
interpretation for many cases in which species do not conform to the TSR.
PMID- 27503716
TI - Regional warming and the thermal regimes of American crocodile nests in the
Tempisque Basin, Costa Rica.
AB - Spatial variation in global climate change makes population-specific responses to
this enigmatic threat pertinent on a regional scale. Organisms with temperature
dependent sex determination (TSD) potentially possess a unique physiological
susceptibility that threatens population viability if rapid environmental effects
on sex ratios render populations non-viable. A heavily male-biased sex ratio for
hatchling American crocodiles of the Tempisque Basin, Costa Rica requires
assessment of how nest temperature affects sex determination at this site, how
females might compensate for these effects when creating nests, and how current
patterns of climate change might alter future sex ratios and survival in
hatchling cohorts. We demonstrate high within-nest variation in temperature but
predict a female bias at hatching based on nest temperatures quantified here.
Further, our data suggest that egg size and metabolic heating associated with
this factor outweighs microhabitat parameters and depth in influencing nest
thermal regimes. Finally, we document regional warming in the Tempisque Basin
over the last 15 years and project that further heating over the next 15 years
will not yield hatchling sex ratios as male biased as those currently found at
this site. Thus, we find no support for nest temperature or climate change as
likely explanations for male-biased American crocodile (Crocodylus acutus) sex
ratios in the Tempisque Basin.
PMID- 27503717
TI - Acute effects of a dopamine/norepinephrine reuptake inhibitor on neuromuscular
performance following self-paced exercise in cool and hot environments.
AB - Dopamine/norepinephrine (DA/NE) reuptake inhibitors have been used to manipulate
the central mechanisms affecting arousal and motivation during exercise. Eight
healthy, physically active males performed 30min fixed-intensity cycling at 50%
Wmax followed by 30min of self paced time trial (TT) with each section
interspersed with a 30 s maximal sprint at 9, 19 and 29min. The DA/NE re-uptake
inhibitor administered was bupropion (BUP) versus a placebo (PLA) in either warm
(32 degrees C, BUP32 or PLA32) or moderate (20 degrees C; BUP20, PLA20) ambient
conditions. Core and skin temperature, heart rate and perceptual responses,
neuromuscular and hormonal measures were assessed at multiple times throughout
the trials and post exercise. Time trial performance remained unchanged across
conditions (12.7-13.1km) although core temperature was elevated in the fixed
intensity section of the trials for BUP32 and BUP20 but continued to rise only in
BUP32 during the time trial reaching 38.6 degrees C (P<0.05). NE increased in all
conditions from pre-exercise with BUP32 values peaking at the end of TT to
1245.3+/-203.1pg/mL (P<0.05) compared to the other conditions. Neuromuscular
responses were similar among conditions although peak force was significantly
reduced from pre (262+/-31N) to post (202+/-31N, P<0.05) exercise along with
contraction duration (22%, P<0.05) in BUP20. We conclude that DA/NE re-uptake
inhibitors influenced thermoregulation in the heat but not exercise performance.
DA/NE re-uptake inhibitors are likely to act centrally to override the inhibitory
signals for the cessation of exercise with these drugs acting peripherally to
reduce the twitch characteristics of skeletal muscle in cooler conditions.
PMID- 27503718
TI - Thermal variation and factors influencing vertical migration behavior in Daphnia
populations.
AB - The antipredator behavior diel vertical migration (DVM), common in aquatic
keystone species Daphnia, involves daily migration from warmer surface waters
before dawn to cooler deeper waters after dusk. Plasticity in Daphnia DVM
behavior optimizes fitness via trade-offs between growth, reproduction, and
predator avoidance. Migration behavior is affected by co-varying biotic and
abiotic factors, including light, predator cues, and anthropogenic stressors
making it difficult to determine each factor's individual contribution to the
variation in this behavior. This study aims to better understand this
ecologically significant behavior in Daphnia by: (1) determining how Daphnia
pulicaria thermal preferences vary within and among natural populations; (2)
distinguishing the role of temperature verses depth in Daphnia vertical
migration; and (3) defining how two anthropogenic stressors (copper and nickel)
impact Daphnia migratory behavior. Simulated natural lake stratification were
constructed in 8L (0.5m tall, 14.5cm wide) water columns to monitor under
controlled laboratory conditions the individual effects of temperature gradients,
depth, and metal stressors on Daphnia vertical migration. Three major findings
are reported. First, while no difference in thermal preference was found among
the four populations studied, within lake populations variability among isolates
was high. Second, decoupling temperature and depth revealed that depth was a
better predictor of Daphnia migratory patterns over temperature. Third, exposure
to environmentally relevant concentrations of copper or nickel inhibited classic
DVM behavior. These findings revealed the high variability in thermal preference
found within Daphnia populations, elucidated the individual roles that depth and
temperature have on migratory behavior, and showed how copper and nickel can
interfere with the natural response of Daphnia to fish predator cues. Thus
contributing to the body of knowledge necessary to predict how natural
populations of Daphnia will be affected by climate related changes in lake
temperatures and increased presence of anthropogenic stressors.
PMID- 27503719
TI - Thermal equilibrium and temperature differences among body regions in European
plethodontid salamanders.
AB - Information on species thermal physiology is extremely important to understand
species responses to environmental heterogeneity and changes. Thermography is an
emerging technology that allows high resolution and accurate measurement of body
temperature, but until now it has not been used to study thermal physiology of
amphibians in the wild. Hydromantes terrestrial salamanders are strongly
depending on ambient temperature for their activity and gas exchanges, but
information on their body temperature is extremely limited. In this study we
tested if Hydromantes salamanders are thermoconform, we assessed whether there
are temperature differences among body regions, and evaluated the time required
to reach the thermal equilibrium. During summers of 2014 and 2015 we analysed 56
salamanders (Hydromantes ambrosii and Hydromantes italicus) using infrared
thermocamera. We photographed salamanders at the moment in which we found them
and 1, 2, 3, 4, 5 and 15min after having kept them in the hands. Body temperature
was equal to air temperature; salamanders attained the equilibrium with air
temperature in about 8min, the time required to reach equilibrium was longer in
individuals with large body size. We detected small temperature differences
between body parts, the head being slightly warmer than the body and the tail
(mean difference: 0.05 degrees C). These salamanders quickly reach the
equilibrium with the environment, thus microhabitat measurement allows obtaining
accurate information on their tolerance limits.
PMID- 27503720
TI - Analysis of the energetic metabolism in cyclic Bedouin goats (Capra hircus):
Nychthemeral and seasonal variations of some haematochemical parameters in
relation with body and ambient temperatures.
AB - Several studies have examined changes in some haematochemical parameters as a
function of the different physiological status (cyclic, pregnant and lactating)
of goats, but no relevant literature has exhaustively investigated these
variations from anestrous to estrous stages in cyclic goats. In this paper, we
report nychthemeral and seasonal variations in ambient and body temperatures, and
in some haematochemical parameters (glycemia, cholesterolemia, triglyceridemia,
creatininemia and uremia) measured during summer, winter and spring, in seven (7)
experimental cyclic female Bedouin goats (Capra hircus) living in the Beni-Abbes
region (Algerian Sahara desert). Cosinor rhythmometry procedure was used to
determine the rhythmic parameters of ambient temperature and haematochemical
parameters. To determine the effect of time of day on the rhythmicity of the
studied parameters, as well as their seasonality, repeated measure analysis of
variance (ANOVA) was applied. The results showed that in spite of the
nychthemeral profile presented by the ambient temperature for each season, the
body temperature remained in a narrow range, thus indicating a successful
thermoregulation. The rhythmometry analysis showed a circadian rhythmicity of
ambient temperature and haematochemical parameters with diurnal acrophases. A
statistically significant effect of the time of day was shown on all studied
haematochemical parameters, except on creatininemia. It was also found that only
uremia, cholesterolemia and triglyceridemia followed the seasonal sexual activity
of the studied ruminant. This study demonstrated the good physiological
adaptation developed by this breed in response to the harsh climatic conditions
of its natural environment.
PMID- 27503721
TI - Effects of daily fluctuating temperatures on the Drosophila-Leptopilina boulardi
parasitoid association.
AB - Koinobiont parasitoid insects, which maintain intimate and long-term
relationships with their arthropod hosts, constitute an association of
ectothermic organisms that is particularly sensitive to temperature variations.
Because temperature shows pronounced natural daily fluctuations, we examined if
experiments based on a constant temperature range can mask the real effects of
the thermal regime on host-parasitoid interactions. The effects of two
fluctuating thermal regimes on several developmental parameters of the Drosophila
larval parasitoid Leptopilina boulardi were analyzed in this study. Regime 1
included a range of 16-23-16 degrees C and regime 2 included a range of 16-21-26
21-16 degrees C (mean temperature 20.1 degrees C) compared to a 20.1 degrees C
constant temperature. Under an average temperature of 20.1 degrees C, which
corresponds to a cold condition of L. boulardi development, we showed that the
success of parasitism is significantly higher under a fluctuating temperature
regime than at constant temperature. A fluctuating regime also correlated with a
reduced development time of the parasitoids. In contrast, the thermal regime did
not affect the ability of Drosophila to resist parasitoid infestation. Finally,
we demonstrated that daily temperature fluctuation prevented the entry into
diapause for this species, which is normally observed at a constant temperature
of 21 degrees C. Overall, the results reveal that constant temperature
experiments can produce misleading results, highlighting the need to study the
thermal biology of organisms under fluctuating regimes that reflect natural
conditions as closely as possible. This is particularly a major issue in host
parasitoid associations, which constitute a good model to understand the effect
of climate warming on interacting species.
PMID- 27503722
TI - Feeding rumen-protected gamma-aminobutyric acid enhances the immune response and
antioxidant status of heat-stressed lactating dairy cows.
AB - This experiment was conducted to investigate the effects of rumen-protected gamma
aminobutyric acid (GABA) on immune function and antioxidant status in heat
stressed dairy cows. Sixty Holstein dairy cows were randomly assigned to 1 of 4
treatments according to a completely randomized block design. The treatments
consisted of 0 (control), 40, 80, or 120mg of GABA/kg DM from rumen-protected
GABA. The trial lasted 10 weeks. The average temperature-humidity indices at
0700, 1400 and 2200h were 78.4, 80.2 and 78.7, respectively. Rectal temperatures
decreased linearly at 0700, 1400, and 2200h with increasing GABA. As the GABA
increased, the immunoglobulin (Ig) A and IgG contents and the proportions of
CD4(+) and CD8(+) T lymphocytes increased linearly (P<0.05), whereas
concentrations of interleukin (IL)-2, IL-4, IL-6 and tumor necrosis factor-alpha
(TNF-alpha) decreased linearly (P<0.05). The activities of superoxide dismutase
(SOD), glutathione-peroxidase (GSH-PX) and total antioxidant capacity (T-AOC)
increased linearly (P<0.05), whereas malondialdehyde (MDA) content decreased
linearly (P<0.05) with increasing GABA. These results indicate that rumen
protected GABA supplementation to heat-stressed dairy cows can improve their
immune function and antioxidant activity.
PMID- 27503723
TI - The effect of skin reflectance on thermal traits in a small heliothermic
ectotherm.
AB - Variation in colour patterning is prevalent among and within species. A number of
theories have been proposed in explaining its evolution. Because solar radiation
interacts with the pigmentation of the integument causing light to either be
reflected or absorbed into the body, thermoregulation has been considered to be a
primary selective agent, particularly among ectotherms. Accordingly, the colour
mediated thermoregulatory hypothesis states that darker individuals will heat
faster and reach higher thermal equilibria while paler individuals will have the
opposite traits. It was further predicted that dark colouration would promote
slower cooling rates and higher thermal performance temperatures. To test these
hypotheses we quantified the reflectance, selected body temperatures, performance
optima, as well as heating and cooling rates of an ectothermic vertebrate,
Lampropholis delicata. Our results indicated that colour had no influence on
thermal physiology, as all thermal traits were uncorrelated with reflectance. We
suggest that crypsis may instead be the stronger selective agent as it may have a
more direct impact on fitness. Our study has improved our knowledge of the
functional differences among individuals with different colour patterns, and the
evolutionary significance of morphological variation within species.
PMID- 27503724
TI - Bicephality, a seldom occurring developmental deformity in Tegenaria atrica
caused by alternating temperatures.
AB - The experiment was aimed at demonstrating the relationship between deformities of
the front part of the prosoma accompanied by changes in the brain structure in
bicephalous Tegenaria atrica and exposure of their embryos to temperature
fluctuations. By exposing spider embryos to alternating temperatures of 14 and 32
degrees C for the first 10 days of embryonic development, we obtained eight two
headed individuals, subsequently divided into three groups according to
morphological differences. We described in detail morphological abnormalities of
the prosoma identified in members of each group. Histological examination
confirmed a close relationship between morphological deformities and the brain
structure of teratogenically changed spiders. The fusion of appendages (pedipalps
and chalicerae) was accompanied by the fusion of corresponding ganglia. The
absence of appendages (pedipalps) was accompanied by the absence of corresponding
ganglia. This correlation may have resulted from previously impaired neuromere
development which led to changes in the morphological structure of the prosoma.
Since no deformities were identified in control animals, it can be concluded that
bicephaly was caused by exposing embryos to alternating temperatures.
PMID- 27503725
TI - The role of nest surface temperatures and the brain in influencing ant metabolic
rates.
AB - Thermal limits of insects can be influenced by recent thermal history: here we
used thermolimit respirometry to determine metabolic rate responses and thermal
limits of the dominant meat ant, Iridomyrmex purpureus. Firstly, we tested the
hypothesis that nest surface temperatures have a pervasive influence on thermal
limits. Metabolic rates and activity of freshly field collected individuals were
measured continuously while ramping temperatures from 44 degrees C to 62 degrees
C at 0.25 degrees C/minute. At all the stages of thermolimit respirometry,
metabolic rates were independent of nest surface temperatures, and CTmax did not
differ between ants collected from nest with different surface temperatures.
Secondly, we tested the effect of brain control on upper thermal limits of meat
ants via ant decapitation experiments ('headedness'). Decapitated ants exhibited
similar upper critical temperature (CTmax) results to living ants (Decapitated
50.3+/-1.2 degrees C: Living 50.1+/-1.8 degrees C). Throughout the temperature
ramping process, 'headedness' had a significant effect on metabolic rate in total
(Decapitated VCO2 140+/-30ulCO2mg(-1)min(-1): Living VCO2 250+/-50 CO2mg(-1)min(
1)), as well as at temperatures below and above CTmax. At high temperatures (>44
degrees C) pre- CTmax the relationships between I. purpureus CTmax values and
mass specific metabolic rates for living ants exhibited a negative slope whilst
decapitated ants exhibited a positive slope. The decapitated ants also had a
significantly higher Q10:25-35 degrees C when compared to living ants (1.91+/
0.43 vs. 1.29+/-0.35). Our findings suggest that physiological responses of ants
may be able to cope with increasing surface temperatures, as shown by metabolic
rates across the thermolimit continuum, making them physiologically resilient to
a rapidly changing climate. We also demonstrate that the brain plays a role in
respiration, but critical thermal limits are independent of respiration levels.
PMID- 27503727
TI - Sitting in the sun: Nest microhabitat affects incubation temperatures in
seabirds.
AB - During incubation parent birds are committed to a nest site and endure a range of
ambient conditions while regulating egg temperatures. Using artificial eggs
containing temperature loggers alongside ambient temperature (Ta) controls,
incubation profiles were determined for four tropical seabird species at
different nest site locations. Camera traps were used for ad-hoc behavioural
incubation observations. Eggs experienced a range of temperatures during
incubation and varied significantly between species and in some cases between
different microhabitats within a species. Such variation has important
consequences in the phenotypic expression of both physical and physiological
traits of chicks, and ultimately species fitness. Exposed nest sites were more
strongly correlated to Tas. Camera traps highlighted different incubation
strategies employed by these species that could be related to trade-offs in
predator defence, feeding habits, and temperature regulation of eggs. This study
provides evidence that species with similar breeding habits could be affected by
environmental stressors in similar ways and that the differences shown in nest
site selection could negate some of these effects. We propose that habitats
providing suitable nest microclimates will become increasingly important for the
successful breeding of seabird species, particularly under predicted climate
change scenarios.
PMID- 27503726
TI - Chronic oral administration of pine bark extract (flavangenol) attenuates brain
and liver mRNA expressions of HSPs in heat-exposed chicks.
AB - Exposure to a high ambient temperature (HT) can cause heat stress, which has a
huge negative impact on physiological functions. Cellular heat-shock response is
activated upon exposure to HT for cellular maintenance and adaptation. In
addition, antioxidants are used to support physiological functions under HT in a
variety of organisms. Flavangenol, an extract of pine bark, is one of the most
potent antioxidants with its complex mixture of polyphenols. In the current
study, chronic (a single daily oral administration for 14 days) or acute (a
single oral administration) oral administration of flavangenol was performed on
chicks. Then the chicks were exposed to an acute HT (40+/-1 degrees C for 3h) to
examine the effect of flavangenol on the mRNA expression of heat-shock protein
(HSP) in the brain and liver. Rectal temperature, plasma aspartate
aminotransferase (AAT), a marker of liver damage, and plasma corticosterone as
well as metabolites were also determined. HSP-70 and -90 mRNA expression, rectal
temperature, plasma AAT and corticosterone were increased by HT. Interestingly,
the chronic, but not the acute, administration of flavangenol caused a declining
in the diencephalic mRNA expression of HSP-70 and -90 and plasma AAT in HT
exposed chicks. Moreover, the hepatic mRNA expression of HSP-90 was also
significantly decreased by chronic oral administration of flavangenol in HT
chicks. These results indicate that chronic, but not acute, oral administration
of flavangenol attenuates HSP mRNA expression in the central and peripheral
tissues due to its possible role in improving cellular protective functions
during heat stress. The flavangenol-dependent decline in plasma AAT further
suggests that liver damage induced by heat stress was minimized by flavangenol.
PMID- 27503729
TI - Black or white? Physiological implications of roost colour and choice in a
microbat.
AB - Although roost choice in bats has been studied previously, little is known about
how opposing roost colours affect the expression of torpor quantitatively. We
quantified roost selection and thermoregulation in a captive Australian
insectivorous bat, Nyctophilus gouldi (n=12) in winter when roosting in black and
white coloured boxes using temperature-telemetry. We quantified how roost choice
influences torpor expression when food was provided ad libitum or restricted in
bats housed together in an outdoor aviary exposed to natural fluctuations of
ambient temperature. Black box temperatures averaged 5.1 degrees C (maximum 7.5
degrees C) warmer than white boxes at their maximum daytime temperature. Bats fed
ad libitum chose black boxes on most nights (92.9%) and on 100% of nights when
food-restricted. All bats used torpor on all study days. However, bats fed ad
libitum and roosting in black boxes used shorter torpor and spent more time
normothermic/active at night than food-restricted bats and bats roosting in white
boxes. Bats roosting in black boxes also rewarmed passively more often and to a
higher skin temperature than those in white boxes. Our study suggests that N.
gouldi fed ad libitum select warmer roosts in order to passively rewarm to a
higher skin temperature and thus save energy required for active midday rewarming
as well as to maintain a normothermic body temperature for longer periods at
night. This study shows that colour should be considered when deploying bat
boxes; black boxes are preferable for those bats that use passive rewarming, even
in winter when food availability is reduced.
PMID- 27503728
TI - Impact of water temperature on the growth and fatty acid profiles of juvenile sea
cucumber Apostichopus japonicus (Selenka).
AB - The present study determined the changes in the fatty acid (FA) profiles of
juvenile sea cucumber Apostichopus japonicus in response to the varied water
temperature. Sea cucumbers with similar size (4.02+/-0.11g) were cultured for 8
weeks at 14 degrees C, 18 degrees C, 22 degrees C and 26 degrees C, respectively.
At the end of the experiment, the specific growth rate (SGR) and the profiles of
FAs in neutral lipids and phospholipids of the juvenile sea cucumbers cultured at
different temperatures were determined. The SGRs of the sea cucumbers cultured at
26 degrees C significantly decreased 46.3% compared to thos cultured at 18
degrees C. Regression analysis showed that the SGR-temperature (T) relationship
can be expressed as SGR=-0.0073T(2)+0.255T -1.0231 (R(2)=0.9936) and the highest
SGR was predicted at 17.5 degrees C. For the neutral lipids, the sum of saturated
FAs (SFAs), monounsaturated FAs (MUFAs) or polyunsaturated FAs (PUFAs) of the sea
cucumbers that were cultured at the water temperature from 18 degrees C-26
degrees C did not change significantly, indicating the insensitivity of FA
profiles for the neutral lipids of sea cucumbers in response to increasing water
temperature. For phospholipids, the sum of PUFAs in the sea cucumbers
dramatically decreased with the gradually increased water temperature. The sum of
SFAs and MUFAs of sea cucumbers, however, increased with the gradually elevated
water temperature. In particular, the contents of highly unsaturated fatty acids
(HUFAs), including eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid
(DHA), in the phospholipids of the sea cucumbers decreased 37.2% and 26.1%,
respectively, when the water temperature increased from 14 degrees C to 26
degrees C. In summary, the sea cucumbers A. japonicus can regulate the FA
compositions, especially the contents of EPA and DHA, in the phospholipids so as
to adapt to varied water temperature.
PMID- 27503730
TI - Nest thermoregulation of the paper wasp Polistes dominula.
AB - Wasps of the genus Polistes build combs without any cover and hence are
insufficiently protected against temperature fluctuations. Due to this fact,
different types of thermoregulation of Polistes dominula nests were investigated
using the modern method of thermography. The study of active mechanisms for nest
thermoregulation revealed no brood incubation or clustering behaviour of P.
dominula. Furthermore, we found out that wing fanning for cooling the nest was
almost undetectable (4 documented cases). However, we could convincingly record
that water evaporation is most effective for nest cooling. By the direct
comparison of active (with brood and adults) and non-active (without brood and
adults) nests, the start of cooling by water evaporation was detected above
maximum outside temperatures of 25 degrees C or at nest temperatures above 35
degrees C. The powerful role of water in nest cooling was manifested by an
average decrease of temperature of single cells of about 8 degrees C and a mean
duration of 7min until the cells reached again their initial temperature. The
investigation of passive thermoregulatory mechanisms revealed that the
architecture of the nest plays an important role. Based on the presented results,
it can be assumed that the vertical orientation of cells helps maintaining the
warmth of nests during the night, whereas the pedicel assists in cooling the nest
during the day. Therefore, our study of nest thermoregulation has revealed that
P. dominula wasps regulate the temperature of their nest actively by evaporative
cooling and passively by a careful site selection and the architecture of their
nests.
PMID- 27503731
TI - Seasonal metabolic acclimatization in the herbivorous desert lizard Uromastyx
philbyi (Reptilia: Agamidea) from western Saudi Arabia.
AB - Many ectotherms adjust their metabolic rate seasonally in association with
variations in environmental temperatures. The range and direction of these
seasonal changes in reptilian metabolic rates are thought to be linked to the
seasonality of activity and energy requirements. The present study was conducted
to measure the standard metabolic rate (SMR) of seasonally-acclimatized Uromastyx
philbyi with different body masses at 20, 25, 30, 35 and 40 degrees C using open
flow respirometry during the four seasons. SMR was mass-dependent. The mean
exponent of mass, "b", in the metabolism-body mass relation was 0.76
(variance=0.0007). Likewise, SMR increased as temperature increased with low Q10
values at high temperatures and high Q10 values at low temperatures. The lowest
and highest Q10 values were achieved for temperature ranges of 30-35 degrees C
for summer-acclimatized dhabbs (Q10=1.6) and 20-25 degrees C for winter
acclimatized dhabbs (Q10=3.9). Seasonal acclimatization effects were obvious at
all temperatures (20-40 degrees C). Winter-acclimatized dhabbs had the lowest
metabolic rates at all temperatures. The seasonal acclimatization patterns
displayed by U. philbyi may represent a valuable adaptation for herbivorous
desert lizards that inhabit subtropical deserts to facilitate activity during
their active seasons and to conserve energy during inactivity at low
temperatures.
PMID- 27503732
TI - Effect of tidal regime on the thermal tolerance of the marine gastropod Lunella
smaragda (Gmelin 1791).
AB - The tidal cycle around New Zealand results in spring low tides consistently
occurring during the hottest part of the day (mid-afternoon) in north-eastern New
Zealand, and during the cooler dawn/dusk periods in the north-west of the
country. We hypothesised that due to mid-afternoon spring low tides, intertidal
populations residing at north-eastern sites would show greater thermotolerance
than their north-west conspecifics. To test this we used the marine gastropod,
Lunella smaragda, which were collected from sites on both the East and West
coasts of the Auckland region and exposed to an acute heat shock. Thermotolerance
was measured as survivorship (LT50), drop down time (time to heat coma) and
thermal stability of the anaerobic energy producing enzyme Tauropine
dehydrogenase. Furthermore, temperature loggers were deployed at each site so as
to record and compare thermal regimes among sites. A strong temperature spike
associated with spring low tide was found at all sites, and maximal temperatures
of all East coast sites were higher than West coast sites (in some case by up to
10 degrees C). In terms of thermotolerance, mortality of L. smaragda occurred at
42 degrees C leading to 100% mortality at 45 degrees C. However, comparison of
LT50 showed snails were equally thermotolerant regardless of site of collection.
Similar results were found in TDH thermal stability with animals from all sites
showing an approximately 80% decrease in enzyme activity after 10min exposure to
42 degrees C. Whilst drop down times were different among sites these were
correlated with animal size as opposed to site of collection. Thus, East coast
populations of L. smaragda appear no more thermotolerant than their West coast
counterparts. Such a result is concerning as maximal temperatures at East coast
sites already exceed the LT50 values of L. smaragda recorded in the lab
suggesting these populations have less of a thermal safety margin.
PMID- 27503733
TI - Brown adipose tissue thermogenesis does not explain the intra-administration
hyperthermic sign-reversal induced by serial administrations of 60% nitrous oxide
to rats.
AB - Initial administration of >=60% nitrous oxide (N2O) to rats promotes hypothermia
primarily by increasing whole-body heat loss. We hypothesized that the drug
promotes heat loss via the tail and might initially inhibit thermogenesis via
brown adipose tissue (BAT), major organs of thermoregulation in rodents.
Following repeated administrations, N2O inhalation evokes hyperthermia underlain
by increased whole-body heat production. We hypothesized that elevated BAT
thermogenesis plays a role in this thermoregulatory sign reversal. Using dual
probe telemetric temperature implants and infrared (IR) thermography, we assessed
the effects of nine repeated 60% N2O administrations compared to control (con)
administrations on core temperature, BAT temperature, lumbar back temperature and
tail temperature. Telemetric core temperature, telemetric BAT temperature, and IR
BAT temperature were reduced significantly during initial 60% N2O inhalation
(p<=0.001 compared to con). IR thermography revealed that acute N2O
administration unexpectedly reduced tail temperature (p=0.0001) and also
inhibited IR lumbar temperature (p<0.0001). In the 9th session, N2O inhalation
significantly increased telemetric core temperature (p=0.007) indicative of a
hyperthermic sign reversal, yet compared to control administrations, telemetric
BAT temperature (p=0.86), IR BAT temperature (p=0.85) and tail temperature
(p=0.47) did not differ significantly. Thus, an initial administration of 60% N2O
at 21 degrees C may promote hypothermia via reduced BAT thermogenesis accompanied
by tail vasoconstriction as a compensatory mechanism to limit body heat loss.
Following repeated N2O administrations rats exhibit a hyperthermic core
temperature but a normalized BAT temperature, suggesting induction of a
hyperthermia-promoting thermogenic adaptation of unknown origin.
PMID- 27503734
TI - Non-linear dual-phase-lag model for analyzing heat transfer phenomena in living
tissues during thermal ablation.
AB - In this article, a non-linear dual-phase-lag (DPL) bio-heat transfer model based
on temperature dependent metabolic heat generation rate is derived to analyze the
heat transfer phenomena in living tissues during thermal ablation treatment. The
numerical solution of the present non-linear problem has been done by finite
element Runge-Kutta (4,5) method which combines the essence of Runge-Kutta (4,5)
method together with finite difference scheme. Our study demonstrates that at the
thermal ablation position temperature predicted by non-linear and linear DPL
models show significant differences. A comparison has been made among non-linear
DPL, thermal wave and Pennes model and it has been found that non-linear DPL and
thermal wave bio-heat model show almost same nature whereas non-linear Pennes
model shows significantly different temperature profile at the initial stage of
thermal ablation treatment. The effect of Fourier number and Vernotte number
(relaxation Fourier number) on temperature profile in presence and absence of
externally applied heat source has been studied in detail and it has been
observed that the presence of externally applied heat source term highly affects
the efficiency of thermal treatment method.
PMID- 27503735
TI - Thermal equilibrium responses in Guzerat cattle raised under tropical conditions.
AB - The literature is very sparse regarding research on the thermal equilibrium in
Guzerat cattle (Bos indicus) under field conditions. Some factors can modify the
physiological response of Guzerat cattle, such as the reactivity of these animals
to handling. Thus, the development of a methodology to condition and select
Guzerat cattle to acclimate them to the routine collection of data without
altering their physiological response was the objective of the preliminary
experiment. Furthermore, the animals selected were used in the main experiment to
determine their thermal equilibrium according to the thermal environment. For
this proposal, the metabolic heat production and heat exchange between the animal
and the environment were measured simultaneously in the field with an indirect
calorimetry system coupled to a facial mask. The results of the preliminary
experiment showed that the respiratory rate could demonstrate that conditioning
efficiently reduced the reactivity of the animals to experimental handling.
Furthermore, the respiratory rate can be used to select animals with less
reactivity. The results of the main experiment demonstrate that the skin, hair
coat surface and expired air temperature depend on the air temperature, whereas
the rectal temperature depends on the time of day; consequently, the sensible
heat flow was substantially reduced from 70 to 20Wm(-2) when the air temperature
increased from 24 to 34 degrees C. However, the respiratory latent heat flow
increased from 10 to 15Wm(-2) with the same temperature increase. Furthermore,
the metabolic heat production remained stable, independent of the variation of
the air temperature; however, it was higher in males than in females (by
approximately 25%). This fact can be explained by the variation of the
ventilation rate, which had a mean value of 1.6 and 2.2Ls(-1) for females and
males, respectively.
PMID- 27503736
TI - The impact of geographical origin of two strains of the herbivore, Eccritotarsus
catarinensis, on several fitness traits in response to temperature.
AB - Adaptation to temperature changes is vital to reduce adverse effects on
individuals, and some may present phenotypic changes, which might be accompanied
with physiological costs in fitness traits. The objective of this study was to
determine whether the two strains of the herbivore Eccritotarsus catarinensis, a
biological control agent against water hyacinth in South Africa, differ in their
responses to temperature according to their geographical origin. We
experimentally quantified the responses of the two strains, at three constant
temperatures: 20 degrees C, 25 degrees C and 30 degrees C, using laboratory
cultures that originated from Brazil and Peru, where climates differ.
Reproductive output, egg hatching rate, sex ratio and longevity were recorded at
each temperature. Fitness traits for both strains were significantly reduced at
30 degrees C compared with 25 degrees C and 20 degrees C in two successive
generations. Nonetheless, Peruvian individuals continued their development at 30
degrees C, whereas Brazilian individuals that succeeded in emerging did not
continue their development. In contrast, sex ratio was unaffected by temperature.
The Peruvian strain of E. catarinensis presented different phenotypes depending
on temperature and was more adapted to extreme high temperature than the
Brazilian strain. The tropical origin of the population induces the insect to
tolerate the extreme high temperature. We suggest that the Peruvian strain could
be better suited for release to control water hyacinth in nature, particularly in
regions where temperature is high.
PMID- 27503737
TI - An efficient and inexpensive method for measuring long-term thermoregulatory
behavior.
AB - Thermoregulatory ability and behavior influence organismal responses to their
environment. By measuring thermal preferences, researchers can better understand
the effects that temperature tolerances have on ecological and physiological
responses to both biotic and abiotic stressors. However, because of funding
limitations and confounders, measuring thermoregulation can often be difficult.
Here, we provide an effective, affordable (~$50 USD per unit), easy to construct,
and validated apparatus for measuring the long-term thermal preferences of
animals. In tests, the apparatus spanned temperatures from 9.29 to 33.94 degrees
C, and we provide methods to further increase this range. Additionally, we
provide simple methods to non-invasively measure animal and substrate
temperatures and to prevent temperature preferences of the focal organisms from
being confounded with temperature preferences of its prey and its humidity
preferences. To validate the apparatus, we show that it was capable of detecting
individual-level consistency and among individual-level variation in the
preferred body temperatures of Southern toads (Anaxyrus terrestris) and Cuban
tree frogs (Osteopilus septentrionalis) over three-weeks. Nearly every aspect of
our design is adaptable to meet the needs of a multitude of study systems,
including various terrestrial amphibious, and aquatic organisms. The apparatus
and methods described here can be used to quantify behavioral thermal
preferences, which can be critical for determining temperature tolerances across
species and thus the resiliency of species to current and impending climate
change.
PMID- 27503738
TI - Thermal tolerance in the Andean toad Rhinella spinulosa (Anura: Bufonidae) at
three sites located along a latitudinal gradient in Chile.
AB - Rhinella spinulosa is one of the anuran species with the greatest presence in
Chile. This species mainly inhabits mountain habitats and is distributed
latitudinally along the western slope of the Andes Range. These habitats undergo
great temperature fluctuations, exerting pressure on the amphibian. To identify
the physiological strategies and thermal behavior of this species, we analyzed
the temperature variables CTmin, CTmax, TTR, tauheat, and taucool in individuals
of three sites from a latitudinal gradient (22 degrees S to 37 degrees S). The
amphibians were acclimated to 10 degrees C and 20 degrees C and fed ad libitum.
The results indicate that the species has a high thermal tolerance range, with a
mean of 38.14+/-1.34 degrees C, a critical thermal maxima of 34.6-41.4 degrees C,
and a critical thermal minima of 2.6-0.8 degrees C, classifying the species as
eurythermic. Furthermore, there were significant differences in CTmax and TTR
only in the northern site. The differences in thermal time constants between
sites are due to the effects of size and body mass. For example, those from the
central site had larger size and greater thermal inertia; therefore, they warmed
and cooled in a slower manner. The wide thermal limits determined in R. spinulosa
confirm that it is a thermo-generalist species, a characteristic that allows the
species to survive in adverse microclimatic conditions. The level of plasticity
in critical temperatures seems ecologically relevant and supports the
acclimatization of thermal limits as an important factor for ectothermic animals
to adapt to climate change.
PMID- 27503739
TI - HIV charity criticises NHS England over "homophobic" PrEP statement.
PMID- 27503740
TI - Identification of the earliest collagen- and plant-based coatings from Neolithic
artefacts (Nahal Hemar cave, Israel).
AB - Mortuary practices in human evolution record cognitive, social changes and
technological innovations. The Neolithic Revolution in the Levant was a watershed
in this domain that has long fascinated the archaeological community. Plaster
modelled skulls are well known at Jericho and several other Neolithic sites, and
in Nahal Hemar cave (Israel, ca. 8200 -7300 cal. BC) excavations yielded six
unique human skulls covered with a black organic coating applied in a net pattern
evoking a headdress. This small cave was used as storage for paraphernalia in the
semi-arid area of the Judean desert and the dry conditions preserved other
artefacts such as baskets coated with a similar dark substance. While previous
analysis had revealed the presence of amino acids consistent with a collagen
signature, in the present report, specific biomarkers were characterised using
combined proteomic and lipid approaches. Basket samples yielded collagen and
blood proteins of bovine origin (Bos genus) and a large sequence coverage of a
plant protein charybdin (Charybdis genus). The skull residue samples were
dominated by benzoate and cinnamate derivatives and triterpenes consistent with a
styrax-type resin (Styrax officinalis), thus providing the earliest known
evidence of an odoriferous plant resin used in combination with an animal
product.
PMID- 27503741
TI - New Insights into Dialysis Vascular Access: Introduction.
PMID- 27503743
TI - Response to: a network meta-analysis of the relative efficacy of treatments for
actinic keratosis of the face or scalp in Europe.
PMID- 27503742
TI - Familial gain-of-function Nav1.9 mutation in a painful channelopathy.
AB - OBJECTIVE: Gain-of-function mutations in Nav1.9 have been identified in three
families with rare heritable pain disorders, and in patients with painful small
fibre neuropathy. Identification and functional assessment of new Nav1.9
mutations will help to elucidate the phenotypic spectrum of Nav1.9
channelopathies. METHODS: Patients from a large family with early-onset pain
symptoms were evaluated by clinical examination and genomic screening for
mutations in SCN9A and SCN11A. Electrophysiological recordings and multistate
modelling analysis were implemented for functional analyses. RESULTS: A novel
Nav1.9 mutation, p.Arg222His, was identified in patients with early-onset pain in
distal extremities including joints and gastrointestinal disturbances, but was
absent from an asymptomatic blood relative. This mutation alters channel
structure by substituting the highly conserved first arginine residue in
transmembrane segment 4 (domain 1), the voltage sensor, with histidine. Voltage
clamp recordings demonstrate a hyperpolarising shift and acceleration of
activation of the p.Arg222His mutant channel, which make it easier to open the
channel. When expressed in dorsal root ganglion neurons, mutant p.Arg222His
channels increase excitability via a depolarisation of resting potential and
increased evoked firing. CONCLUSIONS: This study expands the spectrum of
heritable pain disorders linked to gain-of-function mutations in Nav1.9,
strengthening human validation of this channel as a potential therapeutic target
for pain.
PMID- 27503744
TI - Proton Hopping as the Nerve Conduction Message.
AB - BACKGROUND: The article proposes a new concept explaining nerve conduction
information. The conduction is based upon proton hopping, the fastest known
chemical reaction. A summary of the proton hopping at several parts of the nerve
structure are described. METHODS: The details of each part of the nerve system
are described in the article. RESULTS: A summary of the parts of the nerve
structure involving the role of proton hopping, are expressed to give a complete
picture of the nerve function and the role of proton hopping. CONCLUSION: An
overall description of the function of the nerve is described in terms of the
role of proton hopping as the mechanism of message passage.
PMID- 27503745
TI - Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis.
AB - BACKGROUND The relationship between HLA-DRB1 alleles and asthma is controversial.
The purpose of this study was to evaluate the relationship between HLA-DRB1
alleles and risk of asthma. MATERIAL AND METHODS We searched PubMed, Chinese
National Knowledge Infrastructure (CNKI), Wan Fang (Chinese) database, and
Chinese Biomedical Medical databases (CBM) to find studies on the relationship
between HLA-DRB1 alleles and risk of asthma. We calculated the pooled odds ratio
(OR) and 95% confidence interval (CI) using STATA 12.0. Finally, a total of 24
studies were included in this meta-analysis. RESULTS The results revealed that
DRB1*03 was positively associated with risk of asthma (OR=1.51, 95%CI=1.27-1.80),
and DRB1*15 was negatively associated with risk of asthma (OR=0.63, 95%CI=0.42
0.93), but no association was found in other HLA-DRB1 alleles. Subgroup analysis
by age revealed that DRB1*03, DRB1*04, DRB1*09, and DRB1*15 were associated with
asthma in children. Subgroup analysis by ethnicity showed that DRB1*03 and
DRB1*15 were associated with asthma in whites, and DRB1*07 and DRB1*14 were
associated with asthma in Asians. CONCLUSIONS This results of this meta-analysis
suggest that HLA-DRB1 alleles are associated with asthma.
PMID- 27503746
TI - What predicts a positive response to acupuncture? A secondary analysis of three
randomised controlled trials of insomnia.
AB - OBJECTIVE: Few studies have investigated the predictors of the specific and non
specific effects of acupuncture. The aim of this secondary analysis was to
determine patient characteristics that may predict a better treatment response to
acupuncture for insomnia. METHODS: We pooled the data of three randomised, double
blind, placebo-controlled trials of acupuncture for insomnia to examine
sociodemographic variables, clinical characteristics, baseline sleep-wake
variables, and treatment expectancy in relation to acupuncture response. Subjects
with an improvement in insomnia severity index (ISI) scores of >=8 points from
baseline to 1 week post-treatment were classified as responders. Factors were
compared between responders and non-responders, and also by univariate and
multivariate logistic regression analysis. RESULTS: A total of 116 subjects who
received traditional needle acupuncture were included, of which 37 (31.9%) were
classified as responders. Acupuncture responders had a higher educational level
(p<0.01) and higher baseline ISI score (p<0.05), compared to non-responders. In
the multivariate logistic regression analysis, only the number of years spent in
full-time education remained significant as a predictor of treatment response (OR
1.21, 95% CI 1.06 to 1.38, p<0.01). CONCLUSIONS: Consistent with previous
studies, our data suggest that the response to acupuncture is difficult to
predict. Although the predictive power of educational level is weak overall, our
findings provide potentially valuable information that could be built upon in
further research (including a larger sample size), and may help to inform patient
selection for the treatment of chronic insomnia with acupuncture in the future.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: #NCT00839592; Results,
#NCT00838994; Results, and #NCT01707706; Results.
PMID- 27503747
TI - Patient preference and evidence based decisions on anticoagulant therapy for
atrial fibrillation.
PMID- 27503748
TI - Shave to Save Face.
AB - BACKGROUND: Basal cell carcinoma (BCC) is the most common cutaneous malignancy.
Terminal hair is not routinely removed for assessment of BCCs on the scalp and
yet may obscure the true size of scalp BCCs. This can compromise effective
management. OBJECTIVE: To underscore the importance of removing terminal hair on
the scalp for an accurate assessment of clinical margins of BCC on the scalp.
METHODS: We report 2 cases of cutaneous BCC arising on the scalp. The size of the
malignancies was underestimated because they were masked by hair growth. RESULTS:
Removing terminal hair allowed for a full assessment of the extent of the tumours
on hair-bearing scalp, which had been underestimated by 73% to 80% prior to
shaving. CONCLUSION: Our cases highlight the importance of hair removal for
complete assessment of cutaneous malignancy occurring on hair-bearing skin.
PMID- 27503749
TI - A spectrophotometric assay for monoamine oxidase activity with 2, 4
dinitrophenylhydrazine as a derivatized reagent.
AB - A simple, rapid and reliable spectrophotometry was developed to determine
monoamine oxidase (MAO). In this study, 2,4-dinitrophenylhydrazine (DNPH), a
classic derivatizing reagent, was used to detect MAO-dependent aldehyde
production; and traditional DNPH spectrophotometry was simplified. Benzylamine
and serotonin oxidation were catalyzed by MAO-B and MAO-A, respectively, to
aldehydes. These were derivatized with DNPH, and the corresponding quinones were
further formed by adding NaOH. These DNPH derivatives with large conjugated
structures were directly measured spectrophotometrically at 465 nm and 425 nm,
without the need for precipitating, washing and suspending procedures. The
addition of NaOH caused a red shift of the maximum absorption wavelength of these
derivatives, which reduced the interference of free DNPH. MAO-B protein was as
low as 47.5 MUg in rat liver with correlation coefficients ranging within 0.995
0.999. This method is 2-3 times more sensitive than direct spectrophotometry. The
detection of MAO inhibition through this method showed that IC50 values of
rasagiline are 8.00 * 10(-9) M for MAO-B and 2.59 * 10(-7) M for MAO-A. These
results are similar to the values obtained by direct spectrophotometry. Our study
suggests that DNPH spectrophotometry is suitable to detect MAO activity, and has
the potential for MAO inhibitor screening in the treatment of MAO-mediated
diseases.
PMID- 27503750
TI - Identification and comparative oridonin metabolism in different species liver
microsomes by using UPLC-Triple-TOF-MS/MS and PCA.
AB - Oridonin (ORI) is an active natural ent-kaurene diterpenoid ingredient with
notable anti-cancer and anti-inflammation activities. Currently, a strategy was
developed to identify metabolites and to assess the metabolic profiles of ORI in
vitro using ultra-high-performance liquid chromatography-Triple/time-of-flight
mass spectrometry (UPLC-Triple-TOF-MS/MS). Meanwhile, the metabolism differences
of ORI in the liver microsomes of four different species were investigated using
a principal component analysis (PCA) based on the metabolite absolute peak area
values as the variables. Based on the proposed methods, 27 metabolites were
structurally characterized. The results indicate that ORI is universally
metabolized in vitro, and the metabolic pathway mainly includes dehydration,
hydroxylation, di-hydroxylation, hydrogenation, decarboxylation, and ketone
formation. Overall, there are obvious inter-species differences in types and
amounts of ORI metabolites in the four species. These results will provide basic
data for future pharmacological and toxicological studies of ORI and for other
ent-kauranes diterpenoids. Meanwhile, studying the ORI metabolic differences
helps to select the proper animal model for further pharmacology and
toxicological assessment.
PMID- 27503751
TI - Hepatic Vein Arrival Time for Diagnosis of Liver Cirrhosis: A 10-Year Single
Center Experience With Contrast-Enhanced Sonography.
AB - OBJECTIVES: To evaluate the performance of contrast-enhanced sonography with a
second-generation contrast agent in assessing the severity of chronic diffuse
liver disease and differentiating cirrhotic from noncirrhotic liver disease.
METHODS: Contrast-enhanced sonography was performed after intravenous bolus
injection of a second-generation contrast agent in 14 healthy control
participants and 160 consecutive patients with cirrhotic and noncirrhotic liver
disease (n = 78 and 82, respectively) enrolled between March 2004 and April 2014.
The intensity of enhancement in a main hepatic vein was used to determine hepatic
vein arrival time, time to peak intensity, and peak contrast enhancement.
RESULTS: The hepatic vein arrival time was lower in cirrhotic patients compared
with both noncirrhotic patients and controls (mean +/- SD, 15.0 +/- 2.8, 21.5 +/-
3.4, and 25.6 +/- 4.7 seconds, respectively; P < .05). The hepatic vein arrival
time in noncirrhotic patients was also significantly lower than that in controls
(P < .05). The time to peak intensity was significantly lower in cirrhotic
patients compared with noncirrhotic patients and controls (40.7 +/- 13.7, 49.4 +/
12.8, and 51.2 +/- 13.7 seconds; P < .05). A receiver operating characteristic
curve analysis revealed that the hepatic vein arrival time more accurately
excluded a diagnosis of liver cirrhosis than the time to peak intensity (area
under the receiver operating characteristic curve, 0.953 versus 0.694).
Specifically, a hepatic vein arrival time cutoff value of 17 seconds excluded
liver cirrhosis with 91.1% sensitivity and 93.6% specificity. CONCLUSIONS:
Contrast-enhanced sonography is a valid alternative method for noninvasive
staging of liver diseases. The hepatic vein arrival time could be used to exclude
liver cirrhosis in a clinical setting.
PMID- 27503752
TI - Diagnostic Value of Contrast-Enhanced Sonography for Differentiation of Breast
Lesions: A Meta-analysis.
AB - OBJECTIVES: The purpose of this study was to systematically review and evaluate
the diagnostic accuracy of contrast-enhanced sonography in the differential
diagnosis of benign and malignant breast lesions. METHODS: The scientific
literature databases PubMed and Embase were comprehensively searched for relevant
studies before January 2015. Data were pooled to yield the summary sensitivity,
specificity, and diagnostic odds ratio using meta-analysis software. RESULTS: A
total of 29 studies with 2296 lesions were included in the analysis. The pooled
sensitivity and specificity were 0.88 (95% confidence interval [CI], 0.86-0.90;
inconsistency index [I(2)] = 77.9%) and 0.80 (95% CI, 0.78-0.83; I(2) = 84.0%),
respectively. The pooled diagnostic odds ratio was 30.35 (95% CI, 15.75-58.48;
I(2)= 82.1%), and the area under the summary receiver operating characteristic
curve was 0.9115 (SE, 0.0243). CONCLUSIONS: The comprehensive results suggest
that contrast-enhanced sonography could be a potentially effective method for
differential diagnosis of benign and malignant breast lesions.
PMID- 27503753
TI - Prenatal Diagnosis of an Aortopulmonary Window With an Interrupted Aortic Arch.
AB - A prenatal aortopulmonary window with an interrupted aortic arch was detected in
a 22-week-old fetus. The 3-vessel and trachea view showed a communication between
the ascending aorta and the pulmonary artery. Early postnatal surgery was
successful. A PubMed-based search identified all cases of prenatal aortopulmonary
windows between 2002 and 2015. Nine articles were identified. The average
gestational age at diagnosis was 28 weeks (range, 22-33 weeks). The most frequent
aortopulmonary window was type I (40%). All cases were associated with congenital
heart defects, mainly an interrupted aortic arch (50%). No chromosomal or
extracardiac abnormalities were seen. Prenatal echocardiography is useful for
early diagnosis of an aortopulmonary window. The prognosis depends on the time of
surgery and the nature of the associated anomalies.
PMID- 27503754
TI - Role of Strain Elastography in the Evaluation of Testicular Torsion: An
Experimental Study.
AB - OBJECTIVES: To evaluate the utility of real-time strain elastography in
experimentally induced testicular torsion at different degrees and torsion hours.
METHODS: Thirty-one Wistar albino rats were divided into 4 torsion groups by
twisting left testes (group I, sham operated; group II, 360 degrees ; group III,
720 degrees ; and group IV, 1080 degrees ). Elastography was applied at the 8th
and 24th hours of torsion. Elasticity patterns (pattern 1, soft testis; pattern
2, moderately soft testis; pattern 3, predominantly hard testis; and pattern 4,
almost entirely hard testis) and strain ratios were recorded. Histopathologic
evaluation was done at the 24th hour. Interobserver agreement was analyzed.
RESULTS: Changes in elastographic patterns and strain ratios among groups II,
III, and IV were statistically significant at both hours as determined by both
radiologists (P < .01). Elastographic patterns changed from 2 to 3 in groups II
and III to 4 in group III between the 8th and 24th hours (P < .05), but in group
IV, patterns were reversed, and pattern 1 was observed at both hours.
Pathologically severe necrosis (grade 4) was seen in left testes in group IV. In
the other groups, pathologic grading in the left testes was as follows: mostly
grade 1 in groups I and II and mostly grade 2 in group III. Elastography showed
that right testes were affected in group IV, with significant differences in
elastographic patterns and strain ratios (P < .01). Interobserver agreement for
elastographic patterns in right testes was substantial at the 8th hour (kappa =
0.72) and otherwise excellent (kappa = 0.81-0.85). Concordance of strain ratios
between observers was excellent for right and left testes at the 8th and 24th
hours (intraclass correlation coefficients, 0.990 at the 8th hour and 0.987 at
the 24th hour). CONCLUSIONS: Our results show that real-time strain elastography
can be a complementary method in the evaluation of testicular tissue in
testicular torsion and can guide surgeons in their surgical approach.
PMID- 27503755
TI - On the Physical Basis of Pulmonary Sonographic Interstitial Syndrome.
PMID- 27503756
TI - Contrast-Enhanced Sonographic Characteristics of Hepatic Inflammatory
Pseudotumors.
AB - A hepatic inflammatory pseudotumor, which can be misdiagnosed as a malignant
tumor, is a relatively uncommon tumor with nonspecific imaging manifestations. As
a new diagnostic technique, contrast-enhanced sonography has become increasingly
important in the diagnosis of liver focal lesions. Here we present 3 cases of
histologically confirmed hepatic inflammatory pseudotumors diagnosed with
contrast-enhanced sonography. "Fast-in and centrifugal-out" may be a
characteristic contrast-enhanced sonographic enhancement pattern in the diagnosis
of hepatic inflammatory pseudotumors, which needs confirmation in further
studies.
PMID- 27503757
TI - Interobserver and Intraobserver Agreement on Qualitative Assessments of Right
Ventricular Dysfunction With Echocardiography in Patients With Pulmonary
Embolism.
AB - OBJECTIVES: To evaluate observer agreement using qualitative goal-directed
echocardiographic criteria for right ventricular (RV) dysfunction prognostication
in submassive pulmonary embolism (PE). METHODS: Two emergency physicians and 2
cardiologists independently reviewed 31 packets of goal-directed
echocardiographic video clips consisting of at least 3 windows obtained by
emergency physicians from normotensive patients with PE. Nine packets were
repeated to assess for intraobserver agreement. Right ventricular dysfunction
criteria on goal-directed echocardiography were as follows: RV enlargement was
present, with a right-to-left ventricular basal diameter ratio of 1.0 or higher
and blunting of the apex of the RV in 2 or more different windows; RV systolic
dysfunction was present if the tricuspid annulus moved toward the apex 10 mm or
less and there was RV free wall hypokinesis; and septal deviation was present
with any flattening or deviation of the ventricular septum toward the left
ventricle. RESULTS: Among the 4 participants, there was 83.9% agreement on the
presence or absence of RV enlargement (kappa = 0.84), 74.2% agreement on the
presence or absence of RV systolic dysfunction (kappa = 0.69), and 71.0%
agreement on the presence or absence of septal deviation (kappa = 0.59).
Intraobserver agreement was 100% for each RV dysfunction variable for each
observer (kappa = 1.0). CONCLUSIONS: Agreement was substantial for both severe RV
enlargement and RV systolic dysfunction and moderate for septal deviation. Right
ventricular dysfunction assessment with qualitative goal-directed
echocardiographic criteria is reproducible for PE risk stratification.
PMID- 27503758
TI - Prospective Study Comparing Two Second-Look Ultrasound Techniques: Handheld
Ultrasound and an Automated Breast Volume Scanner.
AB - OBJECTIVES: The aim of this study was to compare the diagnostic performance of
handheld ultrasound (US) and an automated breast volume scanner (ABVS) as second
look US techniques subsequent to preoperative breast magnetic resonance imaging
(MRI). METHODS: We prospectively enrolled patients with breast cancer who
underwent handheld US and ABVS examinations as second-look US modalities for
additional suspicious lesions found via preoperative breast MRI. We reviewed each
second-look US modality independently and evaluated the detection rate of each
modality. We then analyzed the correlation between the detection rate and the MRI
factors (size, distance, and enhancement type). RESULTS: From March to September
2014, both types of second-look US examinations were performed on 40 patients
with breast cancer who had 76 additional suspicious lesions detected via
preoperative breast MRI. The detection rate of the ABVS was higher than that of
handheld US for the second-look examination (94.7% versus 86.8%; P< .05). Among
the 76 total lesions, 7 were only identified by the ABVS, 1 was only found by
handheld US, and 3 were not detected by either the ABVS or handheld US. When we
analyzed the correlation between the detection rate and MRI factors, the only
meaningful factor was the enhancement type. The ability to detect a nonmass
lesion was lower than the ability to detect a mass-type lesion (P < 0.05) for
both the ABVS and handheld US. CONCLUSIONS: For a second-look US examination
subsequent to preoperative breast MRI in patients with breast cancer, the ABVS is
a more efficient modality than handheld US for preoperative evaluations. However,
both techniques have limitations in detecting nonmass lesions.
PMID- 27503759
TI - Isolation of Live Premature Senescent Cells Using FUCCI Technology.
AB - Cellular senescence plays an important role in diverse biological processes such
as tumorigenesis and organismal aging. However, lack of methods to specifically
identify and isolate live senescent cells hampers the precise understanding of
the molecular mechanisms regulating cellular senescence. Here, we report that
utilization of fluorescent ubiquitination-based cell cycle indicator (FUCCI)
technology allows isolation of live premature senescent cells induced by
doxorubicin treatment. Exposure of human foreskin fibroblasts (HFFs) to a low
dose of doxorubicin led to cellular senescent phenotypes including formation of
gamma-H2AX and 53BP1 foci indicative of DNA damage, decreased cell proliferation
and increased senescence-associated beta-galactosidase (SA-beta-gal) activity.
Importantly, doxorubicin-induced senescent cells were arrested at S/G2/M phases
of cell cycle which can be reported by a construct encoding a fragment of
hGeminin fused with monomeric Azami-Green (mAG-hGeminin). Flow cytometric sorting
of GFP(+) cells from doxorubicin-treated HFFs carrying mAG-hGeminin reporter
enabled isolation and enrichment of live senescent cells in the culture. Our
study develops a novel method to identify and isolate live premature senescent
cells, thereby providing a new tool to study cellular senescence.
PMID- 27503760
TI - Huaier restrains proliferative and invasive potential of human hepatoma SKHEP-1
cells partially through decreased Lamin B1 and elevated NOV.
AB - Hepatocellular carcinoma (HCC) is one of the most common cause of malignancy
related mortality worldwide. It is urgently needed to develop potential drugs
with good efficacy and low toxicity for HCC treatment. The anti-tumor effect of
Traditional Chinese Medicine (TCM) has received increasing attention worldwide.
Trametes robiniophila Murr. (Huaier) has been used in TCM for approximately 1,600
years. Clinically, Huaier has satisfactory therapeutic effects in cancer
treatment, especially in HCC. However, the mechanisms underlying the anti-cancer
effect of Huaier remain ill defined. Herein we have demonstrated that Huaier
dramatically inhibited cell proliferation and induced apoptosis in human hepatoma
cell line SKHEP-1. Importantly, Huaier restrained the metastatic capability of
SKHEP-1 cells. Mechanistically, down-regulation of Lamin B1 and up-regulation of
Nephroblastoma overexpressed (NOV) were at least partially responsible for the
inhibitory effect of Huaier on the proliferative and invasive capacity of SKHEP-1
cells. Our finding provided new insights into mechanisms of anti-HCC effect of
Huaier and suggested a new scientific basis for clinical medication.
PMID- 27503761
TI - Fetal Bovine Serum RNA Interferes with the Cell Culture derived Extracellular
RNA.
AB - Fetal bovine serum (FBS) has been used in eukaryotic cell cultures for decades.
However, little attention has been paid to the biological effects associated with
RNA content of FBS on cell cultures. Here, using RNA sequencing, we demonstrate
that FBS contains a diverse repertoire of protein-coding and regulatory RNA
species, including mRNA, miRNA, rRNA, and snoRNA. The majority of them (>70%) are
retained even after extended ultracentrifugation in the preparations of vesicle
depleted FBS (vdFBS) commonly utilized in the studies of extracellular vesicles
(EV) and intercellular communication. FBS-associated RNA is co-isolated with cell
culture derived extracellular RNA (exRNA) and interferes with the downstream RNA
analysis. Many evolutionally conserved FBS-derived RNA species can be falsely
annotated as human or mouse transcripts. Notably, specific miRNAs abundant in
FBS, such as miR-122, miR-451a and miR-1246, have been previously reported as
enriched in cell-culture derived EVs, possibly due to the confounding effect of
the FBS. Analysis of publically available exRNA datasets supports the notion of
FBS contamination. Furthermore, FBS transcripts can be taken up by cultured cells
and affect the results of highly sensitive gene expression profiling
technologies. Therefore, precautions for experimental design are warranted to
minimize the interference and misinterpretations caused by FBS-derived RNA.
PMID- 27503762
TI - Pharmacological treatments of cardiovascular diseases: Evidence from real-life
studies.
AB - The management of chronic cardiovascular diseases has evolved greatly in the last
decades. Over the last thirty years, the management of acute coronary syndrome
has improved, leading to an important lowering of the mortality in the acute
phase of the event. Consequently, the optimal management of the secondary
prevention of acute coronary syndrome has greatly evolved. Moreover, the
increased number of pharmacological alternatives for patients affected by chronic
heart failure and by non-valvular atrial fibrillation reserves a number of
challenges for their correct management. Moreover, these diseases are without any
reasonable doubt the largest contributor to global mortality in the present and
will continue to be it in the future. The aim of this study was to provide the
most updated information of the real-life drug use and their effectiveness. This
review was performed to assess the potential knowledge gaps in the treatments of
these diseases and to indicate potential perspective of pharmaco-epidemiological
research in this area.
PMID- 27503763
TI - Biodegradable ECM-coated PCL microcarriers support scalable human early MSC
expansion and in vivo bone formation.
AB - BACKGROUND AIMS: Human mesenchymal stromal cells or marrow stromal cells (MSCs)
are of great interest for bone healing due to their multi-potency and trophic
effects. However, traditional MSC expansion methods using 2-dimensional monolayer
(MNL) flasks or cell stacks are limited by labor-intensive handling, lack of
scalability, the need for enzymatic cell harvesting and the need for attachment
to a scaffold before in vivo delivery. Here, we present a biodegradable
microcarrier and MSC bioprocessing system that may overcome the abovementioned
challenges. METHODS: We cultured human early MSCs (heMSCs) on biodegradable
polycaprolactone microcarriers (PCL MCs) coated with extracellular matrix (ECM)
and evaluated the in vitro osteogenic differentiation and in vivo bone formation
capacity of ECM-coated PCL MC-bound heMSCs compared with conventional MNL
cultured cells. RESULTS: We found that heMSCs proliferate well on PCL MCs coated
with a fibronectin, poly-l-lysine, and fibronectin (FN+PLL+FN) coating (cPCL
MCs). During in vitro osteogenic induction, heMSCs cultured on cPCL MCs displayed
a 68% increase in specific calcium deposition compared with cultures on MNL. In a
mouse ectopic mineralization model, bone mass was equivalent for MNL-expanded and
cPCL MC-bound heMSC implants but higher in both cases when compared with cell
free cPCL MC implants at 16 weeks post-implantation. In summary, compared with
MNL cultures, biodegradable MC MSC cultures provide the benefits of large-scale
expansion of cells and can be delivered in vivo, thereby eliminating the need for
cell harvesting and use of scaffolds for cell delivery. These results highlight
the promise of delivering heMSCs cultured on cPCL MCs for bone applications.
PMID- 27503764
TI - Bi(OTf)3-catalyzed addition of isocyanides to 2H-chromene acetals: an efficient
pathway for accessing 2-carboxamide-2H-chromenes.
AB - Bismuth triflate (Bi(OTf)3) is identified as an efficient catalyst for the direct
addition of isocyanides to 2H-chromene acetals. The large scope of isocyanides
and chromene acetals makes them suitable substrates in this catalytic system. By
this synthetic strategy, a polyfunctional molecular scaffold, 2-carboxamide-2H
chromenes could be prepared efficiently in one step up to 95% yield. In addition,
this efficient and practical protocol proceeded smoothly in the gram scale even
when the catalytic loading was reduced to 2 mol%.
PMID- 27503765
TI - Scoping the effectiveness and evolutionary obstacles in using plasmid-dependent
phages to fight antibiotic resistance.
AB - AIM: To investigate the potential evolutionary obstacles in the sustainable
therapeutic use of plasmid-dependent phages to control the clinically important
conjugative plasmid-mediated dissemination of antibiotic resistance genes to
pathogenic bacteria. MATERIALS & METHODS: The lytic plasmid-dependent phage PRD1
and the multiresistance conferring plasmid RP4 in an Escherichia coli host were
utilized to assess the genetic and phenotypic changes induced by combined phage
and antibiotic selection. RESULTS & CONCLUSIONS: Resistance to PRD1 was always
coupled with either completely lost or greatly reduced conjugation ability.
Reversion to full conjugation efficiency was found to be rare, and it also
restored the susceptibility to plasmid-dependent phages. Consequently, plasmid
dependent phages constitute an interesting candidate for development of
sustainable anticonjugation/antiresistance therapeutic applications.
PMID- 27503766
TI - Trinuclear nickel and cobalt complexes containing unsymmetrical tripodal
tetradentate ligands: syntheses, structural, magnetic, and catalytic properties.
AB - The coordination chemistries of the tetradentate N2O2-type ligands N-(2
pyridylmethyl)iminodiethanol (H2pmide) and N-(2-pyridylmethyl)iminodiisopropanol
(H2pmidip) have been investigated with nickel(ii) and cobalt(ii/iii) ions. Three
novel complexes prepared and characterized are [(Hpmide)2Ni3(CH3COO)4] (1),
[(Hpmide)2Co3(CH3COO)4] (2), and [(pmidip)2Co3(CH3COO)4] (3). In 1 and 2, two
terminal nickel(ii)/cobalt(ii) units are coordinated to one Hpmide(-) and two
CH3CO2(-). The terminal units are each connected to a central
nickel(ii)/cobalt(ii) cation through one oxygen atom of Hpmide(-) and two oxygen
atoms of acetate ions, giving rise to nickel(ii) and cobalt(ii) trinuclear
complexes, respectively. Trinuclear complexes 1 and 2 are isomorphous. In 3, two
terminal cobalt(iii) units are coordinated to pmidip(2-) and two CH3CO2(-). The
terminal units are each linked to a central cobalt(ii) cation through two oxygen
atoms of pmidip(2-) and one oxygen atom of a bidentate acetate ion, resulting in
a linear trinuclear mixed-valence cobalt complex. 1 shows a weak ferromagnetic
interaction with the ethoxo and acetato groups between the nickel(ii) ions (g =
2.24, J = 2.35 cm(-1)). However, 2 indicates a weak antiferromagnetic coupling
with the ethoxo and acetato groups between the cobalt(ii) ions (g = 2.37, J =
0.5 cm(-1)). Additionally, 3 behaves as a paramagnetic cobalt(ii) monomer, due to
the diamagnetic cobalt(iii) ions in the terminal units (g = 2.53, |D| = 36.0 cm(
1)). No catalytic activity was observed in 1. However, 2 and 3 showed significant
catalytic activities toward various olefins with modest to good yields. 3 was
slightly less efficient toward olefin epoxidation reaction than 2. Also 2 was
used for terminal olefin oxidation reaction and was oxidised to the corresponding
epoxides in moderate yields (34-75%) with conversions ranging from 47-100%. The
cobalt complexes 2 and 3 promoted the O-O bond cleavage to ~75% heterolysis and
~25% homolysis.
PMID- 27503767
TI - Preparation and evaluation of immobilized 4-methylbenzoylcellulose stationary
phases for enantioselective separations.
AB - A photochemical method for immobilizing polysaccharide derivatives on silica gel
has been developed and applied to 4-methylbenzoyl cellulose (PMBC). The
photochemically immobilized materials have been used as chiral stationary phases
(CSPs) for the chromatographic separation of the stereoisomers of chiral
molecules. Through to the immobilization which makes the chromatographic material
insoluble in almost all organic solvents, there no restriction regarding the kind
of solvent used in the mobile phase. This feature permits to considerably extend
the possibilities to improve the selectivity of the separations and or the
solubility of the solute in the mobile phase. The influence of various parameters
such as immobilization process, cross-linker type and amount on the
chromatographic properties and chiral recognition ability of the resulting CSPs
has been investigated using a set of chiral molecules. The impact of the amount
of coated polysaccharide material on chiral recognition ability was also
examined.
PMID- 27503768
TI - Sex hormones modulate neurophysiological correlates of visual temporal attention.
AB - The functional cerebral asymmetry (FCA) in processing targets within rapid serial
visual presentation (RSVP) streams has been reported to fluctuate across the
menstrual cycle, with identification of the second of two closely spaced targets
being impaired when both targets occur in the left or the right hemifield stream
during the luteal phase, while during the menstrual phase identification of the
second target is only impaired for target pairs presented in the right hemifield
stream. This fluctuation has been proposed to result from variations in estradiol
levels. The current study used EEG to investigated whether the cycle-related
fluctuation in RSVP target identification FCA relates to changes in early,
stimulus-driven, bottom-up or in later, top down-driven aspects of FCA. While the
former would be expected to become evident in the early visual evoked potentials
(VEPs) P1 or N1, the latter would be evident in later event-related potentials
(ERPs) such as N2pc or P3. Women performed a dual-stream RSVP task once during
the menstrual phase and once during the follicular phase. Estradiol levels were
determined from saliva samples. In contrast to previous findings, FCA in RSVP
target identification was not affected by cycle phase. However, the impairment in
second-target identification when targets where closely spaced was generally
smaller during the menstrual phase than during the follicular phase. This effect
was matched by shorter peak latencies of P1 VEPs for the menstrual phase, and by
a reduction in the latency of the second-target P3 ERP for closely spaced
relative to widely spaced target pairs, again for the menstrual phase. Results
suggest that in a dual-stream RSVP setup, target identification, early stage
stimulus processing, and target consolidation are affected by cycle phase, but
that the asymmetry of these effects does not differ between menstrual and
follicular phase. The observed cycle-related modulations in neurophysiology and
behavior could relate to the effects of estradiol on the locus ceruleus
norepinephrine (LC-NE) system, which is known to play a major role in arousal,
attention and stress response.
PMID- 27503769
TI - Musical experience facilitates lexical tone processing among Mandarin speakers:
Behavioral and neural evidence.
AB - Music and speech share many sound attributes. Pitch, as the percept of
fundamental frequency, often occupies the center of researchers' attention in
studies on the relationship between music and speech. One widely held assumption
is that music experience may confer an advantage in speech tone processing. The
cross-domain effects of musical training on non-tonal language speakers'
linguistic pitch processing have been relatively well established. However, it
remains unclear whether musical experience improves the processing of lexical
tone for native tone language speakers who actually use lexical tones in their
daily communication. Using a passive oddball paradigm, the present study revealed
that among Mandarin speakers, musicians demonstrated enlarged electrical
responses to lexical tone changes as reflected by the increased mismatch
negativity (MMN) amplitudes, as well as faster behavioral discrimination
performance compared with age- and IQ-matched nonmusicians. The current results
suggest that in spite of the preexisting long-term experience with lexical tones
in both musicians and nonmusicians, musical experience can still modulate the
cortical plasticity of linguistic tone processing and is associated with enhanced
neural processing of speech tones. Our current results thus provide the first
electrophysiological evidence supporting the notion that pitch expertise in the
music domain may indeed be transferable to the speech domain even for native tone
language speakers.
PMID- 27503770
TI - Reducible Polyethylenimine Nanoparticles for Efficient siRNA Delivery in Corneal
Neovascularization Therapy.
AB - The aim of this study is to establish the safe and effective ocular delivery
system of therapeutic small interfering RNA (siRNA) in corneal neovascularization
therapy. The major hurdle present in siRNA-based corneal neovascularization (CNV)
therapy is severe cytotoxicity caused by repetitive drug treatment. A reducible
branched polyethylenimine (rBPEI)-based nanoparticle (NP) system is utilized as a
new siRNA carrier as a hope for CNV therapy. The thiolated BPEI is readily self
crosslinked in mild conditions to make high molecular weight rBPEI thus allowing
the creation of stable siRNA/rBPEI nanoparticles (siRNA-rBPEI-NPs). In the
therapeutic region, the rBPEI polymeric matrix is effectively degraded into
nontoxic LMW BPEI inside the reductive cytosol causing the rapid release of the
encapsulated siRNA into the cytosol to carry out its function. The fluorescent
labeled siRNA-rBPEI-NPs can release siRNA into the entire corneal region after
subconjuctival injection into the eye of Sprague Dawley rats thus confirming the
proof of concept of this system.
PMID- 27503771
TI - Continuous care and patients' basic needs during weaning from mechanical
ventilation: A qualitative study.
AB - BACKGROUND: Mechanical ventilation is associated with a number of risks and
complications. Thus, rapid and safe weaning from mechanical ventilation is of
great importance. Weaning is a complex and challenging process, requiring
continuous care and knowledge of the patient. AIMS: The aim of the present study
was to describe the continuous care process during weaning as well as to analyse
the facilitators and obstacles to the weaning process from start to finish from
the perspective of intensive care unit (ICU) staff, particularly nurses. RESEARCH
DESIGN: Twenty-two ICU staff members, including nurses and physicians, and three
patients hospitalised in the ICU were enrolled in this qualitative study. Semi
structured interviews were used for data collection and the transcripts were
analysed using qualitative content analysis. FINDINGS: 'Continuous care' was
found to be the patients' basic need during weaning from mechanical ventilation.
Uninterrupted, stable, comprehensive and dynamic care and monitoring with
immediate response to all physiological and psychological changes were features
of continuous care. The three main themes identified by this study were time
spent with the patient, comprehensive supervision and maintenance of the quality
of care during shifts. CONCLUSION: Continuous and constant care should be
provided during the weaning process. Such care will help to provide health care
staff with a deeper understanding of the patient and his or her continuous
changes, leading to a timely and favourable response during weaning. To achieve
this goal, skill, communication and organisational changes are essential.
PMID- 27503772
TI - Decreased between-hemisphere connectivity strength and network efficiency in
geriatric depression.
AB - White matter (WM) lesions have been recognized as a key etiological factor in
geriatric depression. However, little is known about the topological pattern
changes of WM in geriatric depression in the remitted state (RGD) and its
relationship to depressive episodes. To address these questions, we acquired
diffusion tensor images in 24 RGD and 24 healthy participants. Among them, 10
patients and 19 healthy controls completed a 1-year follow up. Between-hemisphere
connectivity and graph theoretical methods were used to analyze the data. We
found significantly reduced WM connectivity between the left and right hemisphere
in the RGD group compared with the control group. Those with multiple depression
episodes had greater reduction in between-hemisphere connectivity strength than
those with fewer episodes. In addition, the RGD group had a reduced global
clustering coefficient, global efficiency, and network strength, and an increased
shortest path length compared with the controls. A lower clustering coefficient
was correlated with poorer memory function. The reduction of nodal clustering
coefficient, global efficiency, and network strength in several regions were
associated with slower information processing speed. At 1-year follow up, the
network properties in the RGD subjects were significantly changed suggesting
instability of WM network properties of depressed patients. Together, our study
provides direct evidence of reduced between-hemisphere WM connectivity with
greater depressive episodes, and of alterations of network properties with
cognitive dysfunction in geriatric depression. Hum Brain Mapp 38:53-67, 2017. (c)
2016 Wiley Periodicals, Inc.
PMID- 27503773
TI - Laparoscopic surgery on broken points for uterine sarcoma in the early stage
decrease prognosis.
AB - Uterine sarcoma, a rare solid tumor in uterus, is difficult to identify in the
early stage from some benign uterine tumors, such as uterine fibroids. Hence,
uterine sarcoma may be treated in the same way as uterine fibroids; and this may
not be found until pathological diagnosis. Consequently, this can lead to tumor's
abdominal spread, planting and local invasive growth, resulting in an early
uterine sarcoma, an increased relapse rate after surgery and a decreased
survival. Therefore, it's important to avoid these unintended and iatrogenic
complications through an accurate diagnosis and an appropriate surgical approach.
The surgical staging and a complete resection of the tumor are both important for
patients' prognosis. In this review, we will discuss the laparoscopic surgery for
uterine sarcoma in the early stage and patients' prognosis.
PMID- 27503774
TI - 1H NMR-Linked Metabolomics Analysis of Liver from a Mouse Model of NP-C1 Disease.
AB - Clinical manifestations of Niemann-Pick type C1 (NP-C1) disease include neonatal
hepatosplenomegaly and in some patients progressive liver dysfunction and
failure. This study involved a 1H NMR-linked metabolomics analysis of liver
samples collected from a NP-C1 disease mutant mouse model in order to explore
time-dependent imbalances in metabolic pathways associated with NP-C1 liver
dysfunction, including fibrosis. NP-C1 mutant (Npc1-/-; NP-C1), control (Npc1+/+;
WT), and NP-C1 heterozygous mice (Npc1+/-; HET) were generated from heterozygote
matings. Aqueous extracts of these liver samples collected at time points of 3,
6, 9, and 11 weeks were subjected to high-resolution NMR analysis, and
multivariate (MV) metabolomics analyses of data sets acquired were performed. A
MV random forests (RFs) model effectively discriminated between NP-C1 and a
combined WT/HET hepatic NMR profiles with very high predictive accuracy and
reliability. Key distinguishing features included significant upregulations in
the hepatic concentrations of phenylalanine, tyrosine, glutamate,
lysine/ornithine, valine, threonine, and hypotaurine/methionine, and diminished
levels of nicotinate/niacinamide, inosine, phosphoenolpyruvate, and 3
hydroxyphenylacetate. Quantitative pathway topological analysis confirmed that
imbalances in tyrosine biosynthesis, and hepatic phenylalanine, tyrosine,
glutamate/glutamine, and nicotinate/niacinamide metabolism were involved in the
pathogenesis of NP-C1 disease-associated liver dysfunction/damage. 1H NMR-linked
metabolomics analysis provides valuable biomarker information regarding hepatic
dysfunction or damage in NP-C1 disease.
PMID- 27503775
TI - The Holocene occurrence of Acipenser spp. in the southern North Sea: the
archaeological record.
AB - Archaeological sturgeon remains from the southern North Sea basin used to be
automatically attributed to Acipenser sturio, since this was the only acipenserid
species believed to occur there. These species identifications, however, were in
need of revision after a growing number of indications were found for the
historical presence of Acipenser oxyrinchus in western Europe. In this study,
morphological and genetic data on sturgeon remains from archaeological sites
along the southern North Sea are revised. A large number of Dutch, Belgian,
British and some French archaeological sturgeon remains, dating from the
Mesolithic up to Late Modern times, are morphologically examined and fish sizes
are reconstructed. This study of >7000 acipenserid bones proves the sympatric
occurrence of European sturgeon A. sturio and Atlantic sturgeon A. oxyrinchus in
the southern North Sea at least since the Neolithic (fourth millennium BC
onwards), with A. oxyrinchus remains always outnumbering those of A. sturio.
Human influence is documented by the decrease in finds through time, but no clear
evidence was found for a diachronic change in fish lengths that could possibly be
related to fishing pressure.
PMID- 27503776
TI - The case for investigating social context in laboratory studies of smoking.
AB - BACKGROUND: With increasing frequency, addiction is conceived of as a brain
disease, and such accounts seem especially pertinent with regard to the rapid
delivery of nicotine to the brain via cigarette smoke. Moreover, drug
administration trials (cigarette puffs) suggest that the behavior of smoking
becomes automatized, with individuals developing prototypical approaches to
smoking a cigarette. Compared with presumably more social activities, such as
drinking alcohol, there may be little opportunity for social processes to
influence smoking behavior. However, survey research examining smoking motivation
often reveals a broadly defined 'social' factor and field research suggests that
social context does influence smoking. ARGUMENT: We posit that laboratory smoking
research has largely ignored social contextual factors that may help to
understand better the precise mechanisms underlying smoking behavior and smoking
motivation. METHOD: We reviewed laboratory studies examining the effect of social
context (operationalized as modeling) on smoking behavior. Studies were
identified by searching PsychInfo and Medline using the following keywords:
smoking, nicotine, tobacco, cigarette, consumption, topography, puff, smoking
behavior, cigarettes smoked, modeling, imitation, social context, social
influence and peer pressure. The reference and citation lists of these studies
were then searched to identify additional studies. CONCLUSIONS: Few laboratory
smoking studies target social context. Those few studies indicate that smoking
behavior can be influenced by the presence of others. There is also some evidence
that social context influences the effects of smoking as well as processes
related to self-perception and self-regulation that reinforce smoking and hamper
smoking cessation efforts.
PMID- 27503777
TI - Usefulness of Circulating B-cell-Activating Factor Serial Monitoring in Childhood
Onset Ocular Myasthenia Gravis.
PMID- 27503778
TI - An Atypical Case of Anti-N-Methyl-D-Aspartate Receptor Encephalitis.
PMID- 27503779
TI - In Memoriam - Gordon Barry Pierce, 1925-2015.
PMID- 27503780
TI - Comparison of photodynamic treatment produced cell damage between human breast
cancer cell MCF-7 and its multidrug resistance cell.
AB - BACKGROUND: Multidrug resistance (MDR) of breast cancer is a major obstacle in
chemotherapy of cancer treatments. Recently the anti-tumor effects of Chlorin e6
(Ce6) mediated photodynamic therapy (Ce6-PDT) were reported in skin cancer and
hepatoma in vitro. However, its therapeutic potential in killing human breast
cancer especially those with MDR and the differences between MCF-7 and MCF-7/ADR
after PDT treatment has not been fully investigated. METHODS: MTT assay was used
to measure cell survival rate of MCF-7 cells and MCF-7/ADR cells. Intracellular
reactive oxygen species (ROS) generation was measured by monitoring the
fluorescence intensity of dichlorofluorescein (DCF) by flow cytometry. Nuclear
morphology changes and DNA damage in both MCF-7 and MCF-7/ADR after Ce6-PDT were
analyzed by hochest33342 staining and comet assay. Western blot and
monodansylcadaverine (MDC) staining were used to monitor autophagic response in
MCF-7/ADR. RESULTS: Ce6-PDT induced cell viability decrease, intracellular ROS
generation, and DNA damage in concentration-dependent and cell-specific manner,
and MCF-7 was more sensitive to Ce6-PDT than MCF-7/ADR cells at the same PDT
condition. PDT treatment could trigger cell death via apoptosis in MCF-7 cells
but autophagic cell death in MCF-7/ADR cells. CONCLUSION: These results suggested
that MCF-7 was more sensitive to Ce6-PDT than MCF-7/ADR, and PDT treatment could
trigger apoptotic response in MCF-7 cells, but stimulate autophagic response in
MCF-7/ADR cells.
PMID- 27503781
TI - Observation of clinical efficacy of photodynamic therapy in 3 patients with
refractory plaque-stage mycosis fungoides.
AB - Mycosis fungoides (MF) is one of the most common cutaneous T cell lymphomas
(CTCLs). Currently there are a variety of treatment methods for early-stage MF,
most of which are effective. However, some lesions in plaque-stage react poorly
to conventional therapy. We chose 3 patients with plaque-stage MF who failed
routine therapy, to perform 2-3 times Aminolaevulinic acid-based photodynamic
therapy (ALA-PDT). And it turned out that these patients responded well to ALA
PDT: the skin lesions of 2 patients subsided completely, and the last one had
more than 75% of the lesions eliminated. In conclusion, compared with traditional
therapy, ALA-PDT had tremendous therapeutic effect on refractory plaque-stage MF,
with advantages of less side effects and quicker recovery. Therefore, ALA-PDT was
an effective method for treating refractory plaque-stage MF.
PMID- 27503782
TI - Effectiveness of amphibians as biodiversity surrogates in pond conservation.
AB - Amphibian decline has led to worldwide conservation efforts, including the
identification and designation of sites for their protection. These sites could
also play an important role in the conservation of other freshwater taxa. In 89
ponds in Switzerland, we assessed the effectiveness of amphibians as a surrogate
for 4 taxonomic groups that occur in the same freshwater ecosystems as
amphibians: dragonflies, aquatic beetles, aquatic gastropods, and aquatic plants.
The ponds were all of high value for amphibian conservation. Cross-taxon
correlations were tested for species richness and conservation value, and Mantel
tests were used to investigate community congruence. Species richness,
conservation value, and community composition of amphibians were weakly congruent
with these measures for the other taxonomic groups. Paired comparisons for the 5
groups considered showed that for each metric, amphibians had the lowest degree
of congruence. Our results imply that site designation for amphibian conservation
will not necessarily provide protection for freshwater biodiversity as a whole.
To provide adequate protection for freshwater species, we recommend other
taxonomic groups be considered in addition to amphibians in the prioritization
and site designation process.
PMID- 27503783
TI - Characterization of perioperative infection risk among patients undergoing
radical cystectomy: Results from the national surgical quality improvement
program.
AB - OBJECTIVES: To evaluate the incidence, risk factors, and timing of infections
following radical cystectomy (RC). METHODS: The American College of Surgeons
National Surgical Quality Improvement Project database was queried to identify
patients undergoing RC for bladder cancer from 2006 to 2013. Characteristics
including year of surgery, age, sex body mass index, diabetes, smoking, renal
function, steroid usage, preoperative albumin, preoperative hematocrit,
perioperative blood transfusion (PBT), and operative time were assessed for
association with the risk of infection within 30 days of RC using multivariable
logistic regression. RESULTS: A total of 3,187 patients who had undergone RC were
identified, of whom 766 (24.0%) were diagnosed with a postoperative infection, at
a median of 13 days (interquartile ranges 8-19) after RC. Infections included
surgical site infection (SSI) (404; 12.7%), sepsis/septic shock (405; 12.7%), and
urinary tract infection (UTI) (309; 9.7%). On multivariable analysis, body mass
index>=30kg/m2 (odds ratios [OR] = 1.52; P<0.01), receipt of a PBT (OR = 1.27;
P<0.01), and operative time>=480 minutes (OR = 1.72; P<0.01) were significantly
associated with the risk of infection. When the outcomes of UTI, SSI, and sepsis
were analyzed separately, operative time>=480 minutes remained independently
associated with increased infection risk in each model (OR = 2.11 for UTI, OR =
1.63 for SSI, and OR = 1.80 for sepsis/septic shock; all P<0.05), whereas PBT was
associated with SSI and sepsis/septic shock (OR = 1.33 and OR = 1.29,
respectively; both P< 0.05). CONCLUSIONS: Approximately 25% of patients
undergoing RC experience an infection within 30 days of surgery. Several
potentially modifiable risk factors for infection were identified, specifically
PBT and prolonged operative time, which may represent opportunities for future
care improvement.
PMID- 27503785
TI - Interictal epileptiform discharges have an independent association with cognitive
impairment in children with lesional epilepsy.
AB - OBJECTIVES: The relative contribution of interictal epileptiform discharges
(IEDs) to cognitive dysfunction in comparison with the underlying brain pathology
is not yet understood in children with lesional focal epilepsy. METHODS: The
current study investigated the association of IEDs with intellectual functioning
in 103 children with medication-resistant focal epilepsy. Hierarchical multiple
regression analyses were used to determine the independent contribution of IED
features on intellectual functioning, after controlling for effects of lesional
pathology, epilepsy duration, and medication. Exploratory analyses were conducted
for language and memory scores as well as academic skills available in a subset
of participants. RESULTS: The results reveal that IEDs have a negative
association with IQ with independent, additive effects documented for frequent
and bilaterally distributed IEDs as well as discharge enhancement in sleep. Left
lateralized IEDs had a prominent effect on verbal intelligence, in excess of the
influence of left-sided brain pathology. These effects extended to other
cognitive functions, most prominently for sleep-enhanced IEDs to be associated
with deficits in expressive and receptive language, reading, spelling and
numerical skills. SIGNIFICANCE: Overall, IED effects on cognition were of a
magnitude similar to lesional influences or drug effects (topiramate use). This
study demonstrates an association between IEDs and cognitive dysfunction,
independent of the underlying focal brain pathology.
PMID- 27503786
TI - [Recommendations for the preparation and administration of antituberculosis drugs
in children. Second phase of the Magistral Project of the Spanish Network for the
Study of Paediatric Tuberculosis (pTBred)].
AB - The Spanish Network for the Study of Paediatric Tuberculosis has shown a lack of
national consensus on the treatment of tuberculosis in children, partly due to
the unavailability of paediatric presentations of antituberculosis drugs. The
harmonisation of tuberculosis treatment in children is a priority in Spain. A
joint action is proposed by a group of Spanish experts in childhood tuberculosis
and in the area of Paediatric Pharmacology. To this end, a pTBred-led workgroup
of members from five scientific bodies has been created. Drug pharmaceutical
compounding in oral suspensions or oral solutions are recommended as follows:
isoniazid 50mg/mL, pyrazinamide 100mg/mL, and ethambutol 50mg/mL. Raw materials,
period of validity, and storage conditions are specified. Recommendations for the
use of fixed-dose combination drugs are also established. If oral
solutions/suspensions or fixed-dose combination drugs are not appropriate, the
use of crushed tablets is recommended. Adherence to treatment and optimal dosing
of antituberculosis drugs are critical in the control and eradication of TB. This
multidisciplinary document provides an opportunity to promote the appropriate
treatment of paediatric tuberculosis in Spain, and should become a useful tool
for paediatricians and pharmacists.
PMID- 27503787
TI - [Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: A study
and follow-up of 16 cases].
PMID- 27503784
TI - International consensus on the diagnosis and management of pediatric patients
with hereditary angioedema with C1 inhibitor deficiency.
AB - BACKGROUND: The consensus documents published to date on hereditary angioedema
with C1 inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of
the previous recommendations have not been adapted to pediatric patients. We
intended to produce consensus recommendations for the diagnosis and management of
pediatric patients with C1-INH-HAE. METHODS: During an expert panel meeting that
took place during the 9th C1 Inhibitor Deficiency Workshop in Budapest, 2015
(www.haenet.hu), pediatric data were presented and discussed and a consensus was
developed by voting. RESULTS: The symptoms of C1-INH-HAE often present in
childhood. Differential diagnosis can be difficult as abdominal pain is common in
pediatric C1-INH-HAE, but also commonly occurs in the general pediatric
population. The early onset of symptoms may predict a more severe subsequent
course of the disease. Before the age of 1 year, C1-INH levels may be lower than
in adults; therefore, it is advisable to confirm the diagnosis after the age of
one year. All neonates/infants with an affected C1-INH-HAE family member should
be screened for C1-INH deficiency. Pediatric patients should always carry a C1
INH-HAE information card and medicine for emergency use. The regulatory approval
status of the drugs for prophylaxis and for acute treatment is different in each
country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only
agents licensed for the acute treatment of pediatric patients. Clinical trials
are underway with additional drugs. It is recommended to follow up patients in an
HAE comprehensive care center. CONCLUSIONS: The pediatric-focused international
consensus for the diagnosis and management of C1-INH-HAE patients was created.
PMID- 27503788
TI - Killer-cell immunoglobulin-like receptors genotyping of 127 individuals from
Terceira Island, Azores, Portugal.
AB - One hundred and twenty-seven unrelated Azorean individuals were randomly selected
to study the gene frequencies of Killer-cell immunoglobulin-like receptors (KIR)
in the Azorean (Terceira) population. KIR genotyping was performed by polymerase
chain reaction using commercial sequence-specific oligonucleotide probe kits. All
loci were in HWE, showing no locus-level deviations. The genotype data is
available in the Allele Frequencies Net Database under the population name
"Azores Terceira Island KIR".
PMID- 27503790
TI - Vaccinia virus K1 ankyrin repeat protein inhibits NF-kappaB activation by
preventing RelA acetylation.
AB - The vaccinia virus (VACV) K1 protein inhibits dsRNA-dependent protein kinase
(PKR) activation. A consequence of this function is that K1 inhibits PKR-induced
NF-kappaB activation during VACV infection. However, transient expression of K1
also inhibits Toll-like receptor (TLR)-induced NF-kappaB activation. This
suggests that K1 has a second NF-kappaB inhibitory mechanism that is PKR
independent. This possibility was explored by expressing K1 independently of
infection and stimulating NF-kappaB under conditions that minimized or excluded
PKR activation. K1 inhibited both TNF- and phorbol 12-myristate 13-acetate (PMA)
induced NF-kappaB activation, as detected by transcription of synthetic (e.g.
luciferase) and natural (e.g. CXCL8) genes controlled by NF-kappaB. K1 also
inhibited NF-kappaB activity in PKRkd cells, cells that have greatly decreased
amounts of PKR. K1 no longer prevented IkappaBalpha degradation or NF-kappaB
nuclear translocation in the absence of PKR, suggesting that K1 acted on a
nuclear event. Indeed, K1 was present in the nucleus and cytoplasm of stimulated
and unstimulated cells. K1 inhibited acetylation of the RelA (p65) subunit of NF
kappaB, a nuclear event known to be required for NF-kappaB activation. Moreover,
p65-CBP (CREB-binding protein) interactions were blocked in the presence of K1.
However, K1 did not preclude NF-kappaB binding to oligonucleotides containing
kappaB-binding sites. The current interpretation of these data is that NF-kappaB
promoter interactions still occur in the presence of K1, but NF-kappaB cannot
properly trigger transcriptional activation because K1 antagonizes acetylation of
RelA. Thus, in comparison to all known VACV NF-kappaB inhibitory proteins, K1
acts at one of the most downstream events of NF-kappaB activation.
PMID- 27503791
TI - Leading pancreatic cancer researcher is struck off for fabricating data.
PMID- 27503792
TI - Is State Care an Oxymoron?
PMID- 27503793
TI - Adverse Childhood Experiences and Health in Adulthood in a Rural Population-Based
Sample.
AB - BACKGROUND: Adverse childhood experiences (ACEs), including emotional abuse,
substance abuse in the household, separation or divorce, physical abuse, violence
between adults, mental illness in the household, sexual abuse, or incarceration
of a household member, have the potential to profoundly impact health and well
being in adulthood. To assess whether previously reported relationships between
ACEs and health outcomes withstand validation, we conducted a community-based ACE
study with the unique capacity to link self-reported ACEs and other survey
results to validated health data in an electronic medical record (EMR). METHODS:
Information regarding ACEs and health outcomes was captured from 2013-2014 via a
telephone survey of residents of the predominantly rural northern and central
regions of Wisconsin and electronic abstraction of EMR data. ACE score was
calculated by counting each exposure as one point. We examined the relationship
between ACE score, type, and self-reported and validated health outcomes.
RESULTS: A total of 800 participants completed the telephone survey. Overall, 62%
reported at least one ACE and 15% reported experiencing four or more. All self
reported measures of poor health were associated with increased ACE score. EMR
data were positively correlated with ACE score for increased body mass index and
diagnoses of depression, anxiety, and asthma. In contrast, diagnoses of
hypertension, hypercholesterolemia, myocardial infarction, and skin and other
cancers were inversely related to ACE score. Emotional abuse was the most common
ACE reported followed by substance abuse in the household. ACEs tended to cluster
so that people who reported at least one ACE were likely to have experienced
multiple ACEs. There was no clear correlation between abuse type (e.g., direct
abuse vs. household dysfunction) and health outcomes. CONCLUSIONS: In the first
community-based study to link self-reported ACEs to comprehensive health measures
documented in the medical record, we observed previously reported associations
between childhood adversity and poor outcomes in adulthood, but also noted an
inverse relationship between ACE score and certain medical diagnoses. Potential
explanations for this finding warrant further investigation.
PMID- 27503794
TI - Evaluation of delirium screening tools in geriatric medical inpatients: a
diagnostic test accuracy study.
AB - INTRODUCTION: screening all unscheduled older adults for delirium is recommended
in national guidelines, but there is no consensus on how to perform initial
assessment. AIM: to evaluate the test accuracy of five brief cognitive assessment
tools for delirium diagnosis in routine clinical practice. METHODS: a consecutive
cohort of non-elective, elderly care (older than 65 years) hospital inpatients
admitted to a geriatric medical assessment unit of an urban teaching hospital.
Reference assessments were clinical diagnosis of delirium performed by elderly
care physicians. Routine screening tests were: Abbreviated Mental Test (AMT-10,
AMT-4), 4 A's Test (4AT), brief Confusion Assessment Method (bCAM), months of the
year backwards (MOTYB) and informant Single Question in Delirium (SQiD). RESULTS:
we assessed 500 patients, mean age 83 years (range = 66-101). Clinical diagnoses
were: 93 of 500 (18.6%) definite delirium, 104 of 500 (20.8%) possible delirium
and 277 of 500 (55.4%) no delirium; 266 of 500 (53.2%) were identified as
definite or possible dementia. For diagnosis of definite delirium, AMT-4 (cut
point < 3/4) had a sensitivity of 92.7% (95% confidence interval (CI): 84.8
97.3), with a specificity of 53.7% (95% CI: 48.1-59.2); AMT-10 (<4/10), MOTYB
(<4/12) and SQiD showed similar performance. bCAM had a sensitivity of 70.3% (95%
CI: 58.5-80.3) with a specificity of 91.4% (95% CI: 87.7-94.3). 4AT (>4/12) had a
sensitivity of 86.7% (95% CI: 77.5-93.2) and specificity of 69.5% (95% CI: 64.4
74.3). CONCLUSIONS: short screening tools such as AMT-4 or MOTYB have good
sensitivity for definite delirium, but poor specificity; these tools may be
reasonable as a first stage in assessment for delirium. The 4AT is feasible and
appears to perform well with good sensitivity and reasonable specificity.
PMID- 27503795
TI - A clock network for geodesy and fundamental science.
AB - Leveraging the unrivalled performance of optical clocks as key tools for geo
science, for astronomy and for fundamental physics beyond the standard model
requires comparing the frequency of distant optical clocks faithfully. Here, we
report on the comparison and agreement of two strontium optical clocks at an
uncertainty of 5 * 10(-17) via a newly established phase-coherent frequency link
connecting Paris and Braunschweig using 1,415 km of telecom fibre. The remote
comparison is limited only by the instability and uncertainty of the strontium
lattice clocks themselves, with negligible contributions from the optical
frequency transfer. A fractional precision of 3 * 10(-17) is reached after only
1,000 s averaging time, which is already 10 times better and more than four
orders of magnitude faster than any previous long-distance clock comparison. The
capability of performing high resolution international clock comparisons paves
the way for a redefinition of the unit of time and an all-optical dissemination
of the SI-second.
PMID- 27503796
TI - Proteome mapping of Plasmodium: identification of the P. yoelii remodellome.
AB - Plasmodium associated virulence in the host is linked to extensive remodelling of
the host erythrocyte by parasite proteins that form the "remodellome". However,
without a common motif or structure available to identify these proteins, little
is known about the proteins that are destined to reside in the parasite
periphery, the host-cell cytoplasm and/or the erythrocyte membrane. Here, the
subcellular fractionation of erythrocytic P. yoelii at trophozoite and schizont
stage along with label-free quantitative LC-MS/MS analysis of the whole proteome,
revealed a proteome of 1335 proteins. Differential analysis of the relative
abundance of these proteins across the subcellular compartments allowed us to map
their locations, independently of their predicted features. These results, along
with literature data and in vivo validation of 61 proteins enabled the
identification of a remodellome of 184 proteins. This approach identified a
significant number of conserved remodelling proteins across plasmodium that
likely represent key conserved functions in the parasite and provides new
insights into parasite evolution and biology.
PMID- 27503797
TI - Oral health of Hong Kong children: a historical and epidemiological perspective.
AB - OBJECTIVE: To provide a historical and epidemiological overview of the oral
health of Hong Kong children. METHODS: Literature published before 2014 related
to the oral health of Hong Kong children, supplemented with information accessed
from government-archived oral health reports, was sourced using electronic
databases and hand searches. Dental caries experience, periodontal health, enamel
defects, and malocclusion of Hong Kong children were reviewed. RESULTS: A decline
in the prevalence and extent of dental caries was observed among Hong Kong
schoolchildren and adolescents after the 1960s. Among preschool children,
however, dental caries remains common and the extent appears to have increased.
The periodontal health of Hong Kong children remains unsatisfactory. Recently,
enamel defects/dental fluorosis have considerably reduced. Information about
malocclusion in Hong Kong children is limited. CONCLUSIONS: Since the 1960s,
following public health policies, health promotion activities, and the
introduction of a School Dental Care Service, improvements in the oral health of
schoolchildren are evident. Nonetheless, the oral health of preschool children
remains a concern. Policies and practices to improve the oral health of preschool
children in Hong Kong are required.
PMID- 27503798
TI - Syntheses of pterocarpenes and coumestans via regioselective cyclodehydration.
AB - A highly efficient synthetic route to pterocarpenes and coumestans is described.
BCl3-mediated dehydrative cyclization of 1,3-diaryloxyacetones under mild
conditions permitted regioselective ring closure to afford 3-((2
iodoaryloxy)methyl)benzofurans which were converted to the corresponding
pterocarpenes by Pd-catalyzed intramolecular direct arylation. The subsequent
benzylic oxidation led to coumestans. This sequence was applied to the formal
syntheses of coumestrol and the proposed structure of plicadin as well as total
syntheses of flemichapparins B and C.
PMID- 27503799
TI - Development and pilot-testing of a new tool to screen psoriasis patients for the
presence of psoriatic arthritis: the Simple Psoriatic Arthritis Screening (SiPAS)
questionnaire.
PMID- 27503800
TI - Glucose level determines excitatory or inhibitory effects of adiponectin on
arcuate POMC neuron activity and feeding.
AB - Adiponectin regulates glucose and lipid metabolism, acting against metabolic
syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts
on the brain including hypothalamic arcuate nucleus (ARC), where
proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several
studies have examined intracerebroventricular (ICV) injection of adiponectin and
reported opposite effects, increase or decrease of food intake. These reports
used different nutritional states. The present study aimed to clarify whether
adiponectin exerts distinct effects on food intake and ARC POMC neurons depending
on the glucose concentration. Adiponectin was ICV injected with or without
glucose for feeding experiments and administered to ARC slices with high or low
glucose for patch clamp experiments. We found that adiponectin at high glucose
inhibited POMC neurons and increased food intake while at low glucose it exerted
opposite effects. The results demonstrate that glucose level determines
excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity
and feeding.
PMID- 27503801
TI - Reciprocity in spatial evolutionary public goods game on double-layered network.
AB - Spatial evolutionary games have mainly been studied on a single, isolated
network. However, in real world systems, many interaction topologies are not
isolated but many different types of networks are inter-connected to each other.
In this study, we investigate the spatial evolutionary public goods game (SEPGG)
on double-layered random networks (DRN). Based on the mean-field type arguments
and numerical simulations, we find that SEPGG on DRN shows very rich interesting
phenomena, especially, depending on the size of each layer, intra-connectivity,
and inter-connected couplings, the network reciprocity of SEPGG on DRN can be
drastically enhanced through the inter-connected coupling. Furthermore, SEPGG on
DRN can provide a more general framework which includes the evolutionary dynamics
on multiplex networks and inter-connected networks at the same time.
PMID- 27503802
TI - Identification of structural determinants of NAD(P)H selectivity and lysine
binding in lysine N(6)-monooxygenase.
AB - l-lysine (l-Lys) N(6)-monooxygenase (NbtG), from Nocardia farcinica, is a flavin
dependent enzyme that catalyzes the hydroxylation of l-Lys in the presence of
oxygen and NAD(P)H in the biosynthetic pathway of the siderophore nocobactin.
NbtG displays only a 3-fold preference for NADPH over NADH, different from well
characterized related enzymes, which are highly selective for NADPH. The
structure of NbtG with bound NAD(P)(+) or l-Lys is currently not available.
Herein, we present a mutagenesis study targeting M239, R301, and E216. These
amino acids are conserved and located in either the NAD(P)H binding domain or the
l-Lys binding pocket. M239R resulted in high production of hydrogen peroxide and
little hydroxylation with no change in coenzyme selectivity. R301A caused a 300
fold decrease on kcat/Km value with NADPH but no change with NADH. E216Q
increased the Km value for l-Lys by 30-fold with very little change on the kcat
value or in the binding of NAD(P)H. These results suggest that R301 plays a major
role in NADPH selectivity by interacting with the 2'-phosphate of the adenine
ribose moiety of NADPH, while E216 plays a role in l-Lys binding.
PMID- 27503803
TI - Glycan structure of Gc Protein-derived Macrophage Activating Factor as revealed
by mass spectrometry.
AB - Disagreement exists regarding the O-glycan structure attached to human vitamin D
binding protein (DBP). Previously reported evidence indicated that the O-glycan
of the Gc1S allele product is the linear core 1 NeuNAc-Gal-GalNAc-Thr
trisaccharide. Here, glycan structural evidence is provided from glycan linkage
analysis and over 30 serial glycosidase-digestion experiments which were followed
by analysis of the intact protein by electrospray ionization mass spectrometry
(ESI-MS). Results demonstrate that the O-glycan from the Gc1F protein is the same
linear trisaccharide found on the Gc1S protein and that the hexose residue is
galactose. In addition, the putative anti-cancer derivative of DBP known as Gc
Protein-derived Macrophage Activating Factor (GcMAF, which is formed by the
combined action of beta-galactosidase and neuraminidase upon DBP) was analyzed
intact by ESI-MS, revealing that the activating E. coli beta-galactosidase
cleaves nothing from the protein-leaving the glycan structure of active GcMAF as
a Gal-GalNAc-Thr disaccharide, regardless of the order in which beta
galactosidase and neuraminidase are applied. Moreover, glycosidase digestion
results show that alpha-N-Acetylgalactosamindase (nagalase) lacks endoglycosidic
function and only cleaves the DBP O-glycan once it has been trimmed down to a
GalNAc-Thr monosaccharide-precluding the possibility of this enzyme removing the
O-glycan trisaccharide from cancer-patient DBP in vivo.
PMID- 27503804
TI - Neuoroprotective efficacies by KUS121, a VCP modulator, on animal models of
retinal degeneration.
AB - Retinitis pigmentosa (RP) is one of the leading causes of adult blindness and has
no established therapy. We have shown that valosin-containing protein (VCP)
modulators, Kyoto University Substances (KUSs), ameliorated abnormally low ATP
levels by inhibiting the ATPase of VCP, thereby protected several types of cells,
including retinal neurons, from cell death-inducing insults. In this study, we
found that KUS121, one of the VCP modulators, effectively protects photoreceptors
both morphologically and functionally, in two animal models of retinal
degeneration, rd12 mice and RP rabbits with a rhodopsin (Pro347Leu) mutation. In
rd12 mice, KUS121 suppressed the loss of photoreceptors, not only rods but also
cones, as well as the visual function deterioration. Significant protective
effects existed even when the medication was started in later stages of the
disease. In RP rabbits, KUS121 suppressed thinning of the outer nuclear layer and
maintained visual function. In the retinas treated with KUS121, suppression of
endoplasmic reticulum stress, activation of mammalian target of rapamycin and
suppression of disease-associated apoptosis were evident. The ability of KUS121
to protect photoreceptors, especially cones, even in later stages of the disease
may contribute to the preservation of central vision in RP patients, which is
important for quality of vision.
PMID- 27503805
TI - Defining myocardial tissue abnormalities in end-stage renal failure with cardiac
magnetic resonance imaging using native T1 mapping.
AB - Noninvasive quantification of myocardial fibrosis in end-stage renal disease is
challenging. Gadolinium contrast agents previously used for cardiac magnetic
resonance imaging (MRI) are contraindicated because of an association with
nephrogenic systemic fibrosis. In other populations, increased myocardial native
T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial
fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age-
and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1
relaxation times and feature tracking-derived global longitudinal strain as
potential markers of fibrosis were compared and associated with cardiac
biomarkers. Left ventricular mass indices were higher in the hemodialysis than
the control group. Global, Septal and midseptal T1 times were all significantly
higher in the hemodialysis group (global T1 hemodialysis 1171 +/- 27 ms vs. 1154
+/- 32 ms; septal T1 hemodialysis 1184 +/- 29 ms vs. 1163 +/- 30 ms; and
midseptal T1 hemodialysis 1184 +/- 34 ms vs. 1161 +/- 29 ms). In the hemodialysis
group, T1 times correlated with left ventricular mass indices. Septal T1 times
correlated with troponin and electrocardiogram-corrected QT interval. The peak
global longitudinal strain was significantly reduced in the hemodialysis group
(hemodialysis -17.7+/-5.3% vs. -21.8+/-6.2%). For hemodialysis patients, the peak
global longitudinal strain significantly correlated with left ventricular mass
indices (R = 0.426), and a trend was seen for correlation with galectin-3, a
biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis
patients consistent with myocardial fibrosis can be determined noninvasively and
associated with multiple structural and functional abnormalities.
PMID- 27503806
TI - Hypoxia-inducible factor-1alpha promotes glomerulosclerosis and regulates COL1A2
expression through interactions with Smad3.
AB - The function of hypoxia-inducible factor-1alpha (HIF-1alpha) in chronic kidney
disease is disputed. Here we report that interactions of HIF-1alpha with
transforming growth factor-beta (TGF-beta) signaling may promote its fibrotic
effects. Knockout of HIF-1alpha is protective against glomerulosclerosis and
glomerular type-I collagen accumulation in a mouse podocyte ablation model.
Transcriptional analysis of cultured renal cells showed that alpha2(I) collagen
expression is directly regulated by HIF-1alpha binding to a functional hypoxia
responsive element in its promoter at -335 relative to the transcription start
site. Activation of COL1A2 transcription by HIF-1alpha occurred in the absence of
hypoxia and is strongly enhanced by TGF-beta signaling. TGF-beta, in addition to
increasing HIF-1alpha levels, increased both HIF-1alpha binding to the COL1A2
promoter and HIF-1alpha N-terminal transactivation domain activity. These effects
of TGF-beta on HIF-1alpha were inhibited in Smad3-null mouse embryonic
fibroblasts, suggesting a requirement for Smad3. Phosphorylated Smad3 also
associated with the -335 hypoxia-responsive element of the COL1A2 promoter
independent of a Smad DNA binding sequence. Smad3 binding to the -335 hypoxia
responsive element required HIF-1alpha both in vitro and in kidney lysate from
the disease model, suggesting formation of an HIF-1alpha-Smad3 transcriptional
complex. Thus, HIF-1alpha-Smad3 has a novel interaction in glomerulosclerosis.
PMID- 27503807
TI - Polydopamine-Coated Porous Microspheres Conjugated with Immune Stimulators for
Enhanced Cytokine Induction in Macrophages.
AB - Polydopamine-coated porous microsphere (PPM) is investigated as a simple and
versatile immobilization strategy for immune-stimulating biomolecules to enhance
delivery efficiency and immune-stimulating effects such as cytokine induction in
macrophages. The PPMs, with diameters of about 2 MUm, exhibit simultaneous and
efficient incorporation of biomolecules (nucleotides and proteins), which is
comparable to that achieved using microspheres carrying biomolecules internally
by virtue of their porous structure. Ovalbumin-conjugated PPMs are internalized
into macrophages efficiently and selectively via the phagocytic pathway, without
any noticeable toxicity. Internalized CpG oligodeoxynucleotide (ODN)-conjugated
PPMs (PPM-CpG) greatly enhance the induction of selected cytokines (TNF-alpha and
IL-6) in RAW 264.7 cells compared to that by the soluble CpG ODN and ionic
complexes. Therefore, PPMs generated in this study may serve as effective
carriers of immune-stimulating biomolecules such as diverse toll-like receptor
agonists.
PMID- 27503808
TI - Band gap bowing in NixMg1-xO.
AB - Epitaxial transparent oxide NixMg1-xO (0 <= x <= 1) thin films were grown on
MgO(100) substrates by pulsed laser deposition. High-resolution synchrotron X-ray
diffraction and high-resolution transmission electron microscopy analysis
indicate that the thin films are compositionally and structurally homogeneous,
forming a completely miscible solid solution. Nevertheless, the composition
dependence of the NixMg1-xO optical band gap shows a strong non-parabolic bowing
with a discontinuity at dilute NiO concentrations of x < 0.037. Density
functional calculations of the NixMg1-xO band structure and the density of states
demonstrate that deep Ni 3d levels are introduced into the MgO band gap, which
significantly reduce the fundamental gap as confirmed by optical absorption
spectra. These states broaden into a Ni 3d-derived conduction band for x > 0.074
and account for the anomalously large band gap narrowing in the NixMg1-xO solid
solution system.
PMID- 27503809
TI - Metastatic prostatic adenocarcinoma with neuroendocrine differentiation to
meningioma.
AB - The diagnosis of a tumor-to-tumor metastasis in the central nervous system most
commonly involves metastasis to a meningioma. These combined lesions are often
radiographically unsuspected and mimic a meningioma. Most commonly, the source of
metastatic disease are carcinomas from the lung and breast. To our knowledge,
fewer than a half dozen cases of metastatic prostatic adenocarcinoma to a
meningioma have been documented in the literature. This report documents a 67
year-old man who presented with worsening confusion and altered mental status,
accompanied by symptoms of increased urinary frequency, incontinence, and
difficulty urinating. Imaging revealed a mass at the base of the bladder and an
intracranial lesion, surrounded by edema, which was initially suspicious for
intracranial metastasis of prostate cancer. Due to worsening neurological
symptoms, the patient underwent craniotomy to remove the intracranial mass. The
mass was comprised of a meningothelial meningioma, World Health Organization
Grade I, accompanied by atypical epithelioid cells which demonstrated
immunoreactivity to prostate specific antigen, chromogranin and neuron specific
enolase antibodies, consistent with a metastatic prostatic adenocarcinoma with
neuroendocrine differentiation. The patient suffered severe neurological
complications post-operatively, developed multiple metastases and expired
12months later. The report reviews current theories as to why meningiomas are the
most common host tumor for tumor-to-tumor metastases in the brain and reviews the
literature on previously reported cases involving metastatic prostatic
adenocarcinoma.
PMID- 27503810
TI - NF-kappaB deregulation in splenic marginal zone lymphoma.
AB - Splenic marginal zone lymphoma is a rare mature B-cell malignancy involving the
spleen, bone marrow and blood. Over the past years, the rapid expansion of
sequencing technologies allowing the genome-wide assessment of genomic,
epigenetic and transcriptional changes has revolutionized our understanding of
the biological basis of splenic marginal zone lymphoma by providing a
comprehensive and unbiased view of the genes/pathways that are deregulated in
this disease. NF-kappaB is a family of transcription factors that plays critical
roles in development, survival, and activation of B lymphocytes. Consistent with
the physiological involvement of NF-kappaB signalling in proliferation and
commitment of mature B-cells to the marginal zone of the spleen, many oncogenic
mutations involved in constitutive activation of the NF-kappaB pathway were
recently identified in splenic marginal zone lymphoma. This review describes the
progress in understanding the mechanism of NF-kappaB activation in splenic
marginal zone lymphoma, including molecular, epigenetic and post-transcriptional
modifications of NF-kappaB genes and of upstream pathways, and discusses how
information gained from these efforts has provided new insights on potential
targets of diagnostic, prognostic and therapeutic relevance for splenic marginal
zone lymphoma.
PMID- 27503816
TI - [The Neural Mechanism of Emotional Sweating].
AB - The autonomic nervous system mediates blood pressure, heart rate, and sweat
secretion, which are strongly modulated by the limbic system. Moreover, the
limbic system plays an important role in generating emotion. Therefore,
monitoring autonomic activities, such as palmar sweating, could be useful to
evaluate emotional responses. Palmar sweating is otherwise known as emotional
sweating, and it's monitored for lie-detection or psychological therapy. The
present review will be helpful for neurologists, psychiatrists, and psychologists
seeking to understand the neural mechanism of emotional sweating.
PMID- 27503811
TI - Effects of acute alcohol withdrawal on nest building in mice selectively bred for
alcohol withdrawal severity.
AB - Nest building has been used to assess thermoregulatory behavior and positive
motivational states in mice. There are known genetic influences on ethanol
withdrawal severity as well as individual/thermoregulatory nest building.
Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1,
WSR-2) mice were selectively bred for high vs low handling-induced convulsion
(HIC) severity, respectively, during withdrawal from chronic ethanol vapor
inhalation. They also differ in HIC severity during withdrawal from an acute,
4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of
ethanol dose-dependently impaired nest building over the initial 24h of
withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In
two further studies, acute ethanol withdrawal suppressed nest building for up to
two days in WSP-1 females. Deficits in nest building from ethanol were limited to
the initial 10h of withdrawal in WSR-1 females and to the initial 24h of
withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up
to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building
deficits in female mice from the first replicate could not be explained by a
general decrease in locomotor behavior. These results suggest that nest building
is a novel behavioral phenotype for indexing the severity of acute ethanol
withdrawal, and that genes contributing to this trait differ from those affecting
acute withdrawal HIC severity.
PMID- 27503817
TI - [Emotion Disorders and Abnormal Perspiration].
AB - This article reviewed the relationship between emotional disorders and abnormal
perspiration. First, I focused on local brain areas related to emotional
processing, and summarized the functions of the emotional network involving those
local areas. Functional disorders followed by the damage in the amygdala,
orbitofrontal cortex, and insular cortex were reviewed, including related
abnormal perspiration. I then addressed the mechanisms of how autonomic disorders
influence emotional processing. Finally, possible future directions for
integrated understanding of the connection between neural activities and bodily
reactions were discussed.
PMID- 27503818
TI - [Functional Neuroimaging of Sweating].
AB - Central mechanisms of thermal and emotional sweating has been elucidated by using
functional MRI in healthy human subjects. The hypothalamus (preoptic region) was
specifically activated during thermal sweating, whereas prefrontal regions,
insula, and anterior cingulate were activated during emotional sweating. Both
thermal and emotional sweating were associated with activation in the dorsal
midbrain and in the rostral lateral medulla. These results suggested that
sweating in human represents not only sympathetic activation but also integrates
emotional function, internal awareness, and attentional arousal in humans.
PMID- 27503819
TI - [Decision Making and Electrodermal Activity].
AB - Decision making is aided by emotions. Bodily responses, such as sweating,
heartbeat, and visceral sensation, are used to monitor the emotional state during
decision making. Because decision making in dairy life is complicated and
cognitively demanding, these bodily signals are thought to facilitate the
decision making process by assigning positive or negative values for each of the
behavioral options. The sweat response in a decision making task is measured by
skin conductance response (SCR). SCR in decision making is divided into two
categories: anticipatory SCR is observed before making decisions, and
reward/punishment SCR is observed after the outcome of the decision is perceived.
Brain lesion studies in human revealed that the amygdala and ventromedial
prefrontal cortex are important in decision making. Patients with lesinon in the
amygdala exhibit neither the anticipatory nor reward/punishment SCRs, while
patients with the ventromedial prefrontal lesions have deficits only in the
anticipatory SCRs. Decision making tasks and SCR analysis have contributed to
reveal the implicit aspects of decision making. Further research is necessary for
clarifying the role of explicit process of decision making and its relationship
with the implicit process.
PMID- 27503820
TI - [Biofeedback Therapy and Sweat].
AB - Biofeedback training is a technique through which one can learn to control
usually uncontrollable inner body functions, such as brain waves, heart rate or
electrodermal activity (EDA). These 'hidden' biological signals are measured from
a participant and fed back during the training, e.g., through visual and auditory
changes on a computer screen. With practice, the participant learns to control
this feedback, and ultimately to control their bodily responses without needing
the feedback. In this article, the application of EDA biofeedback will be
introduced as a therapy for specific neurological conditions.
PMID- 27503821
TI - [Role of Reelin during Layer Formation in the Cerebral Neocortex].
AB - Reelin controls the neuronal layer formation in the developing cerebral
neocortex. The Reelin glycoprotein is mainly secreted from Cajal-Retzius cells in
the marginal zone, and it guides the proper aggregation of the migrating neurons
in a birth-dependent "inside-out" manner. Reelin also regulates the final process
of neuronal migration (terminal translocation and somal translocation) by
activating integrin and N-cadherin. It is also expressed around the
subventricular zone and it controls the behavior of the migrating neurons.
PMID- 27503822
TI - [The Social Costs of Dementia in Japan: Focusing on the Informal Care Cost].
AB - Due to the rapid increase of the number in people with dementia, social costs of
dementia are also expected to rise. In 2014, the social cost of dementia in Japan
was estimated to be 145,140 billion yen, 40 % of which was spent on informal
care. To investigate whether each intervention is worth the investment, more
research on aspects like cost-effective analysis is expected to be undertaken.
PMID- 27503823
TI - [An Autopsy Case of Globular Glial Tauopathy Presenting with Amyotrophic Lateral
Sclerosis with Dementia].
AB - We report an autopsy case of globular glial tauopathy (GGT) presenting clinically
with amyotrophic lateral sclerosis (ALS) with dementia. A 79-year-old female
developed weakness in the right upper limb, which progressed gradually. She
developed apathy and speech disorder at 80 years of age. On neurological
examination, she showed signs of upper and lower motor neuron disorder and
dementia, but no extrapyramidal signs. The clinical diagnosis was ALS with
dementia. The autopsy revealed left predominant marked atrophy of the frontal
lobe due to severe neuronal loss and Gliosis. Immunohistochemistry using anti-4
repeat tau antibody revealed numerous globular glial inclusions. Severe
neurodegeneration in the primary motor cortex and corticospinal tract was
observed. There were distinctive tau-positive inclusions in both Betz and
anterior horn cells. TDP-43-positive inclusions in motor neurons were not
detected. Sequence analysis of the tau gene revealed no mutations in exons 1-5,
7, 9-13, or the adjacent intronic sequences. GGT can cause a clinical phenotype
of ALS with dementia. (Received December 28, 2015; Accepted February 23, 2016;
Published August 1, 2016).
PMID- 27503824
TI - [Effective Microvascular Decompression of the Trigeminal Nerve in a Patient with
SUNCT].
AB - A 43-year-old man presented with severe, saw-tooth pattern pain around the right
eye that started with conjunctival injection, lacrimation and nasal discharge,
lasting for about 1 hour, 4 months after the initial onset of lancinating pain in
the same area. The patient was diagnosed with SUNCT (short-lasting unilateral
neuralgiform headache attacks with conjunctival injection and tearing) according
to the International Classification of Headache Disorders 3rd edition (beta
version). The symptoms improved in 2 months but recurred 6 months later. He
developed a toxic eruption after receiving a variety of antiepileptic agents
including lamotrigine, which suggested refractory SUNCT. Head magnetic resonance
imaging (MRI) showed neurovascular compression (NVC) involving the right
trigeminal nerve. Microvascular decompression (MVD) was performed, and the pain
was relieved postoperatively. MVD should be considered when treating refractory
SUNCT because NVC may be involved in some cases. (Received February 29, 2016;
Accepted April 4, 2016; Published August 1, 2016).
PMID- 27503825
TI - [A Case of Spontaneous Putaminal Hemorrhage Responsible for the Rupture of
Charcot Artery].
PMID- 27503826
TI - Inter- and Intra-Observer Agreement in Ultrasound BI-RADS Classification and Real
Time Elastography Tsukuba Score Assessment of Breast Lesions.
AB - Our aim was to prospectively evaluate inter- and intra-observer agreement between
Breast Imaging Reporting and Data System (BI-RADS) classifications and Tsukuba
elasticity scores (TSs) of breast lesions. The study included 164 breast lesions
(63 malignant, 101 benign). The BI-RADS classification and TS of each breast
lesion was assessed by the examiner and twice by three reviewers at an interval
of 2 months. Weighted kappa values for inter-observer agreement ranged from
moderate to substantial for BI-RADS classification (kappa = 0.585-0.738) and was
substantial for TS (kappa = 0.608-0.779). Intra-observer agreement was almost
perfect for ultrasound (US) BI-RADS (kappa = 0.847-0.872) and TS (kappa = 0.879
0.914). Overall, individual reviewers are highly self-consistent (almost perfect
intra-observer agreement) with respect to BI-RADS classification and TS, whereas
inter-observer agreement was moderate to substantial. Comprehensive training is
essential for achieving high agreement and minimizing the impact of subjectivity.
Our results indicate that breast US and real-time elastography can achieve high
diagnostic performance.
PMID- 27503827
TI - Nearly half of US pediatric trials are unfinished or unpublished, study finds.
PMID- 27503828
TI - Significantly Accelerated Wound Healing of Full-Thickness Skin Using a Novel
Composite Gel of Porcine Acellular Dermal Matrix and Human Peripheral Blood
Cells.
AB - Here we report the fabrication of a novel composite gel from decellularized gal
gal-knockout porcine skin and human peripheral blood mononuclear cells (hPBMCs)
for full-thickness skin wound healing. Decellularized skin extracellular matrix
(ECM) powder was prepared via chemical treatment, freeze drying, and
homogenization. The powder was mixed with culture medium containing hyaluronic
acid to generate a pig skin gel (PSG). The effect of the gel in regeneration of
full-thickness wounds was studied in nude mice. We found significantly
accelerated wound closure already on day 15 in animals treated with PSG only or
PSG + hPBMCs compared to untreated and hyaluronic acid-treated controls (p <
0.05). Addition of the hPBMCs to the gel resulted in marked increase of host
blood vessels as well as the presence of human blood vessels. At day 25,
histologically, the wounds in animals treated with PSG only or PSG + hPBMCs were
completely closed compared to those of controls. Thus, the gel facilitated
generation of new skin with well-arranged epidermal cells and restored bilayer
structure of the epidermis and dermis. These results suggest that porcine skin
ECM gel together with human cells may be a novel and promising biomaterial for
medical applications especially for patients with acute and chronic skin wounds.
PMID- 27503829
TI - Bayesian bent-cable growth mixture tobit models for longitudinal data with
skewness and detection limit: application to AIDS studies.
AB - This paper presents a new Bayesian methodology for identifying a transition
period for the development of drug resistance to antiretroviral drug or therapy
in HIV/AIDS studies or other related fields. Estimation of such a transition
period requires an availability of longitudinal data where growth trajectories of
a response variable tend to exhibit a gradual change from a declining trend to an
increasing trend rather than an abrupt change. We assess this clinically
important feature of the longitudinal HIV/AIDS data using the bent-cable
framework within a growth mixture Tobit model. To account for heterogeneity of
drug resistance among subjects, the parameters of the bent-cable growth mixture
Tobit model are also allowed to differ by subgroups (subpopulations) of patients
classified into latent classes on the basis of trajectories of observed viral
load data with skewness and left-censoring. The proposed methods are illustrated
using real data from an AIDS clinical study. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27503830
TI - Environmental and mucosal microbiota and their role in childhood asthma.
AB - BACKGROUND: High microbial diversity in the environment has been associated with
lower asthma risk, particularly in children exposed to farming. It remains
unclear whether this effect operates through an altered microbiome of the mucosal
surfaces of the airways. METHODS: DNA from mattress dust and nasal samples of 86
school age children was analyzed by 454 pyrosequencing of the 16S rRNA gene
fragments. Based on operational taxonomic units (OTUs), bacterial diversity and
composition were related to farm exposure and asthma status. RESULTS: Farm
exposure was positively associated with bacterial diversity in mattress dust
samples as determined by richness (P = 8.1 * 10-6 ) and Shannon index (P = 1.3 *
10-5 ). Despite considerable agreement of richness between mattress and nasal
samples, the association of richness with farming in nasal samples was restricted
to a high gradient of farm exposure, that is, exposure to cows and straw vs no
exposure at all. In mattress dust, the genera Clostridium, Facklamia, an
unclassified genus within the family of Ruminococcaceae, and six OTUs were
positively associated with farming. Asthma was inversely associated with richness
[aOR = 0.48 (0.22-1.02)] and Shannon index [aOR = 0.41 (0.21-0.83)] in mattress
dust and to a lower extent in nasal samples [richness aOR 0.63 = (0.38-1.06),
Shannon index aOR = 0.66 (0.39-1.12)]. CONCLUSION: The stronger inverse
association of asthma with bacterial diversity in mattress dust as compared to
nasal samples suggests microbial involvement beyond mere colonization of the
upper airways. Whether inhalation of metabolites of environmental bacteria
contributes to this phenomenon should be the focus of future research.
PMID- 27503831
TI - The neurotrophin receptor signaling endosome: Where trafficking meets signaling.
AB - Neurons are the largest cells in the body and form subcellular compartments such
as axons and dendrites. During both development and adulthood building blocks
must be continually trafficked long distances to maintain the different regions
of the neuron. Beyond building blocks, signaling complexes are also transported,
allowing for example, axons to communicate with the soma. The critical roles of
signaling via ligand-receptor complexes is perhaps best illustrated in the
context of development, where they are known to regulate polarization, survival,
axon outgrowth, dendrite development, and synapse formation. However, knowing
'when' and 'how much' signaling is occurring does not provide the complete story.
The location of signaling has a significant impact on the functional outcomes.
There are therefore complex and functionally important trafficking mechanisms in
place to control the precise spatial and temporal aspects of many signal
transduction events. In turn, many of these signaling events affect trafficking
mechanisms, setting up an intricate connection between trafficking and signaling.
In this review we will use neurotrophin receptors, specifically TrkA and TrkB, to
illustrate the cell biology underlying the links between trafficking and
signaling. Briefly, we will discuss the concepts of how trafficking and signaling
are intimately linked for functional and diverse signaling outputs, and how the
same protein can play different roles for the same receptor depending on its
localization. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437,
2017.
PMID- 27503832
TI - Vaccine Coverage for United States Infants at Milestone Ages: Missed
Opportunities for Vaccination.
AB - We used a claims database to assess coverage for rotavirus (RV), diphtheria
tetanus-acellular pertussis, and pneumococcal conjugate vaccines among infants in
the United States. Similar coverage was seen until 7 months of age, after which
RV coverage lagged. Missed opportunities for vaccination at well-child visits
were found to vary by age.
PMID- 27503833
TI - Enhanced protective role in materials with gradient structural orientations:
Lessons from Nature.
AB - Living organisms are adept at resisting contact deformation and damage by
assembling protective surfaces with spatially varied mechanical properties, i.e.,
by creating functionally graded materials. Such gradients, together with multiple
length-scale hierarchical structures, represent the two prime characteristics of
many biological materials to be translated into engineering design. Here, we
examine one design motif from a variety of biological tissues and materials where
site-specific mechanical properties are generated for enhanced protection by
adopting gradients in structural orientation over multiple length-scales, without
manipulation of composition or microstructural dimension. Quantitative
correlations are established between the structural orientations and local
mechanical properties, such as stiffness, strength and fracture resistance; based
on such gradients, the underlying mechanisms for the enhanced protective role of
these materials are clarified. Theoretical analysis is presented and corroborated
through numerical simulations of the indentation behavior of composites with
distinct orientations. The design strategy of such bioinspired gradients is
outlined in terms of the geometry of constituents. This study may offer a
feasible approach towards generating functionally graded mechanical properties in
synthetic materials for improved contact damage resistance. STATEMENT OF
SIGNIFICANCE: Living organisms are adept at resisting contact damage by
assembling protective surfaces with spatially varied mechanical properties, i.e.,
by creating functionally-graded materials. Such gradients, together with multiple
length-scale hierarchical structures, represent the prime characteristics of many
biological materials. Here, we examine one design motif from a variety of
biological tissues where site-specific mechanical properties are generated for
enhanced protection by adopting gradients in structural orientation at multiple
length-scales, without changes in composition or microstructural dimension. The
design strategy of such bioinspired gradients is outlined in terms of the
geometry of constituents. This study may offer a feasible approach towards
generating functionally-graded mechanical properties in synthetic materials for
improved damage resistance.
PMID- 27503834
TI - Epigenetics and nutrition-related epidemics of metabolic diseases: Current
perspectives and challenges.
AB - We live in a world fascinated by the relationship between disease and nutritional
disequilibrium. The subtle and slow effects of chronic nutrient toxicity are a
major public health concern. Since food is potentially important for the
development of "metabolic memory", there is a need for more information on the
type of nutrients causing adverse or toxic effects. We now know that metabolic
alterations produced by excessive intake of some nutrients, drugs and chemicals
directly impact epigenetic regulation. We envision that understanding how
metabolic pathways are coordinated by environmental and genetic factors will
provide novel insights for the treatment of metabolic diseases. New methods will
enable the assembly and analysis of large sets of complex molecular and clinical
data for understanding how inflammation and mitochondria affect bioenergetics,
epigenetics and health. Collectively, the observations we highlight indicate that
energy utilization and disease are intimately connected by epigenetics. The
challenge is to incorporate metabolo-epigenetic data in better interpretations of
disease, to expedite therapeutic targeting of key pathways linking nutritional
toxicity and metabolism. An additional concern is that changes in the parental
phenotype are detectable in the methylome of subsequent offspring. The effect
might create a menace to future generations and preconceptional considerations.
PMID- 27503835
TI - Choice of non-medic to run radiology school was "ill conceived," says royal
college.
PMID- 27503836
TI - Drosophila wing imaginal discs respond to mechanical injury via slow InsP3R
mediated intercellular calcium waves.
AB - Calcium signalling is a highly versatile cellular communication system that
modulates basic functions such as cell contractility, essential steps of animal
development such as fertilization and higher-order processes such as memory. We
probed the function of calcium signalling in Drosophila wing imaginal discs
through a combination of ex vivo and in vivo imaging and genetic analysis. Here
we discover that wing discs display slow, long-range intercellular calcium waves
(ICWs) when mechanically stressed in vivo or cultured ex vivo. These slow
imaginal disc intercellular calcium waves (SIDICs) are mediated by the inositol-3
phosphate receptor, the endoplasmic reticulum (ER) calcium pump SERCA and the key
gap junction component Inx2. The knockdown of genes required for SIDIC formation
and propagation negatively affects wing disc recovery after mechanical injury.
Our results reveal a role for ICWs in wing disc homoeostasis and highlight the
utility of the wing disc as a model for calcium signalling studies.
PMID- 27503837
TI - A flexible parametric approach to examining spatial variation in relative
survival.
AB - Most of the few published models used to obtain small-area estimates of relative
survival are based on a generalized linear model with piecewise constant hazards
under a Bayesian formulation. Limitations of these models include the need to
artificially split the time scale, restricted ability to include continuous
covariates, and limited predictive capacity. Here, an alternative Bayesian
approach is proposed: a spatial flexible parametric relative survival model. This
overcomes previous limitations by combining the benefits of flexible parametric
models: the smooth, well-fitting baseline hazard functions and predictive
ability, with the Bayesian benefits of robust and reliable small-area estimates.
Both spatially structured and unstructured frailty components are included.
Spatial smoothing is conducted using the intrinsic conditional autoregressive
prior. The model was applied to breast, colorectal, and lung cancer data from the
Queensland Cancer Registry across 478 geographical areas. Advantages of this
approach include the ease of including more realistic complexity, the feasibility
of using individual-level input data, and the capacity to conduct overall, cause
specific, and relative survival analysis within the same framework. Spatial
flexible parametric survival models have great potential for exploring small-area
survival inequalities, and we hope to stimulate further use of these models
within wider contexts. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27503838
TI - Assessment of Early Tumour Shrinkage: Ready for Integration in the Treatment
Strategy for Metastatic Renal Cell Carcinoma?
PMID- 27503839
TI - Re: Prostate Cancer Detection with Magnetic Resonance-ultrasound Fusion Biopsy:
The Role of Systematic and Targeted Biopsies.
PMID- 27503840
TI - Improved Reporting of Randomized Controlled Trials in the Urologic Literature.
AB - BACKGROUND: Well-designed randomized controlled trials (RCTs) have the potential
to provide high-quality evidence to inform questions of therapy and prevention,
but this potential is contingent on the use of appropriate methods and
transparent reporting. OBJECTIVE: To systematically assess the quality of urology
RCT reporting and identify trends over time. DESIGN, SETTING, AND PARTICIPANTS:
All RCTs published in four leading urology journals in 2013 were identified and
compared to a prior analysis of studies from 1996 and 2004. Two reviewers
abstracted data based on the Consolidated Standards of Reporting Trials (CONSORT)
checklist. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A summary reporting
score (range: 0-22) for each study was determined. Mean overall scores for 1996,
2004, and 2013 were compared using analysis of variance. We used chi2 to compare
the reporting frequency of individual criteria. RESULTS AND LIMITATIONS: Mean
CONSORT scores for RCTs were 15.6+/-2.0 in 2013 (n=82), 12.0+/-0.3 in 2004
(n=87), and 10.2+/-0.3 in 1996 (n=65); p<0.01. Key deficiencies remain in
reporting methods of allocation concealment and group assignment (selection
bias), and blinding of participants, personnel, and outcome assessors
(performance and detection bias). Study limitations are potential reviewer bias
resulting from lack of journal deidentification and the relatively low number of
studies reviewed. CONCLUSIONS: There has been a substantial improvement in
reporting quality of RCTs in urology since CONSORT. Some methodological criteria
remain underreported, and increased efforts are necessary to further this
improvement. PATIENT SUMMARY: Treatment decisions are often based on data from
randomized controlled trials. We looked at whether these trials in urology are
transparent in reporting their design and conduct using a framework known as the
CONSORT criteria and found significant improvements over time. Some areas of
deficiency remain, and our paper aimed to highlight these drawbacks to promote
continued high-quality research.
PMID- 27503841
TI - Comparison of luminescence property of gamma-ray irradiated Tb3+ -doped and Ce3+
co-doped potassium halide single crystals.
AB - Single crystals of KCl and KBr singly and doubly doped with Tb3+ and Ce3+ ,
respectively, were successfully grown using the Bridgeman technique. This work
reports the comparative luminescence behavior and optical absorption
characterization of non-irradiated and gamma-ray-irradiated single crystals of
these materials. The existing defect and the defect created by gamma-ray
irradiation were monitored by optical absorption spectra. The excitation and
emission spectra of these materials were measured at room temperature with a
spectrofluorometer and the pertaining results were compared. The F-band
comparison was made when bleached with F-light for 2 mins. The trap-level changes
in KCl and KBr when it is singly and doubly doped enabled us to draw conclusions
on the nature of the defect and on the recombination processes involved.
PMID- 27503842
TI - Seeing is Believing: Tracking Translation Dynamics In Vivo.
AB - Translation is a crucial step in transmitting genetic information from mRNA to
functional protein. Four recent papers provide novel imaging approaches to
directly observe translation of single mRNAs in real time in live cells, and
represent a powerful toolkit to dissect the molecular mechanisms of translation
regulation.
PMID- 27503843
TI - Neuroanatomical bases of effortful control: evidence from a large sample of young
healthy adults using voxel-based morphometry.
AB - Effortful control (EC) is a base of individuality in cognition and psychological
adjustment. EC is defined as a capacity to control responses and behaviors. We
investigated associations between individual differences of EC and regional gray
and white matter volume (rGMV/rGMV) in 374 men and 306 women (age, 20.61 +/- 1.82
years) using Japanese version of Effortful control scale (J-ECS). J-ECS consists
of three subscales such as inhibitory control (IC), activation control (ACTC),
and attentional control (ATC). Results showed that (a) IC was associated with
larger rGMV in the dorsal part of anterior cingulate cortex (dACC), the
supplementary motor area (SMA) and the pre SMA and larger rWMV in the dACC, (b)
ACTC was correlated with smaller rGMV in the insula and the putamen, and (c) ATC
was associated with larger rWMV in the inferior frontal gyrus, orbital frontal
gyrus, ACC, and insula. Our study revealed key neuroanatomical correlations
between EC and rGMV and rWMV.
PMID- 27503844
TI - The Risk of Hepatotoxicity, New Onset Diabetes and Rhabdomyolysis in the Era of
High-Intensity Statin Therapy: Does Statin Type Matter?
AB - The 2013 American College of Cardiology/American Heart Association guidelines on
cholesterol management have placed greater emphasis on high-intensity statin
dosing for those with known cardiovascular disease or diabetes mellitus.
Differences in risk of hepatotoxicity, new onset diabetes and rhabdomyolysis
specifically between the high-intensity statins and the most common moderate
intensity statin, simvastatin, were not found to a significant degree in this
review. Rather, baseline characteristics and drug-drug interactions (DDIs) appear
to be more important regarding the risk of these adverse effects. Pharmacogenetic
differences in statin metabolism may explain individual susceptibility, however
genetic testing is not felt to be cost effective at this time. More importantly,
statin choice should consider concomitant use of the many prevalent CYP3A4
inhibitors or inducers, and when present, rosuvastatin selection is recommended
to reduce DDIs and risk of statin-induced adverse effects.
PMID- 27503845
TI - DCLK1 phosphorylates the microtubule-associated protein MAP7D1 to promote axon
elongation in cortical neurons.
AB - Doublecortin-like kinase 1 (DCLK1) is a member of the neuronal microtubule
associated doublecortin (DCX) family and functions in multiple stages of neural
development including radial migration and axon growth of cortical neurons. DCLK1
is suggested to play the roles in part through its protein kinase activity, yet
the kinase substrates of DCLK1 remain largely unknown. Here we have identified
MAP7D1 (microtubule-associated protein 7 domain containing 1) as a novel
substrate of DCLK1 by using proteomic analysis. MAP7D1 is expressed in developing
cortical neurons, and knockdown of MAP7D1 in layer 2/3 cortical neurons results
in a significant impairment of callosal axon elongation, but not of radial
migration, in corticogenesis. We have further defined the serine 315 (Ser 315) of
MAP7D1 as a DCLK1-induced phosphorylation site and shown that overexpression of a
phosphomimetic MAP7D1 mutant in which Ser 315 is substituted with glutamic acid
(MAP7D1 S315E), but not wild-type MAP7D1, fully rescues the axon elongation
defects in Dclk1 knockdown neurons. These data demonstrate that DCLK1
phosphorylates MAP7D1 on Ser 315 to facilitate axon elongation of cortical
neurons. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.
PMID- 27503846
TI - StemCell KeepTM Is Effective for Cryopreservation of Human Embryonic Stem Cells
by Vitrification.
AB - Safe and stable cryopreservation is critical for research involving human
embryonic stem cells (hESCs). Dimethyl sulfoxide (DMSO) is a popular
cryoprotective agent; however, its cytotoxicity cannot be ignored. Thus, there is
a need for an alternate cryoprotectant. We reported previously that a novel
cryopreservation reagent, StemCell KeepTM (SCK), was effective for cryopreserving
human induced pluripotent stem cells (hiPSCs) by vitrification. Because hESCs and
hiPSCs are not identical, the current study examined the use of SCK on hESCs.
hESCs cryopreserved with SCK were thawed and cultured on SNL 76/7 cells, which
were derived from a mouse fibroblast STO cell line transformed with neomycin
resistance and murine LIF genes. After cryopreservation, cultured hESCs were
assessed for their attachment ability and characterized by alkaline phosphatase
(AP) and immunocytochemical (ICC) staining, fluorescence-activated cell sorting
(FACS), reverse transcription polymerase chain reaction (RT-PCR), and
karyotyping. The proliferation of SCK-cryopreserved hESCs cultured on SNL cells,
or in feeder-free conditions, was higher than that of cells preserved in a
solution of 2 M DMSO, 1 M acetamide, and 3 M propylene glycol (DAP). The cell
number with SCK-cryopreserved hESCs was about twice that of hESCs cryopreserved
in DAP. The pluripotency of SCK-cryopreserved hESCs was similar to that of DAP
cryopreserved hESCs based on AP staining. Data from ICC, FACS, and RT-PCR
analyses showed that stem cell markers were continually expressed on SCK
cryopreserved hESCs. The teratoma assay showed that SCK-cryopreserved hESCs
differentiated into three germ layers. Furthermore, SCK-cryopreserved hESCs had
normal karyotypes. These data indicate that SCK was effective for
cryopreservation of hESCs by vitrification.
PMID- 27503847
TI - Surgical Valvotomy Versus Balloon Valvuloplasty for Congenital Aortic Valve
Stenosis: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Optimal initial treatment for congenital aortic valve stenosis in
children remains unclear between balloon aortic valvuloplasty (BAV) and surgical
aortic valvotomy (SAV). METHODS AND RESULTS: We performed a contemporary
systematic review and meta-analysis to compare survival in children with
congenital aortic valve stenosis. Secondary outcomes included frequency of at
least moderate regurgitation at hospital discharge as well as rates of aortic
valve replacement and reintervention. Single- and dual-arm studies were
identified by a search of PubMed (Medline), Embase, and the Cochrane database.
Overall 2368 patients from 20 studies were included in the analysis, including
1835 (77%) in the BAV group and 533 (23%) in the SAV group. There was no
difference between SAV and BAV in hospital mortality (OR=0.98, 95% CI 0.5-2.0,
P=0.27, I(2)=22%) or frequency of at least moderate aortic regurgitation at
discharge (OR=0.58, 95% CI 0.3-1.3, P=0.09, I(2)=54%). Kaplan-Meier analysis
showed no difference in long-term survival or freedom from aortic valve
replacement but significantly more reintervention in the BAV group (10-year
freedom from reintervention of 46% [95% CI 40-52] for BAV versus 73% [95% CI 68
77] for SAV, P<0.001). Results were unchanged in a sensitivity analysis
restricted to infants (<1 year of age). CONCLUSIONS: Although higher rates of
reintervention suggest improved outcomes with SAV, indications for reintervention
may vary depending on initial intervention. When considering the benefits of a
less-invasive approach, and clinical equipoise with respect to more clinically
relevant outcomes, these findings support the need for a randomized controlled
trial.
PMID- 27503848
TI - Long-Term Prognosis of Brugada-Type ECG and ECG With Atypical ST-Segment
Elevation in the Right Precordial Leads Over 20 Years: Results From the
Circulatory Risk in Communities Study (CIRCS).
AB - BACKGROUND: Brugada syndrome is recognized as being associated with sudden
cardiac death; however, the prevalence of non-type 1 Brugada-type ECG (BrS) or
atypical ST-segment elevation in the right precordial leads (STERP) and the long
term prognosis for those patients remain unknown. METHODS AND RESULTS: We
analyzed standard 12-lead ECGs of 7178 apparently healthy participants (age range
40-64 years) who underwent health checkups from 1982 to 1986 in the Circulatory
Risk in Communities Study, a prospective, large, community-based cohort study in
Japan. ECGs with J point amplitude >=0.2 mV in the right precordial leads were
divided into 3 groups: (1) type 1 BrS, (2) type 2 or 3 BrS (non-type 1 BrS), and
(3) STERP. The others served as the non-ST-segment elevation group. We identified
8 participants (0.1%) with type1 BrS, 84 (1.2%) with non-type 1 BrS, and 228
(3.2%) with STERP. During a median follow-up of 18.7 years (133 987.0 person
years), sudden cardiac death was observed in no participants (0.0%) with type 1
BrS, in 1 (1.2%) with non-type 1 BrS, in 7 (3.1%) with STERP, and in 50 (0.7%)
with non-ST-segment elevation. Participants with STERP had a markedly elevated
risk of sudden cardiac death (multivariable hazard ratio 3.9, 95% CI 1.7-9.0).
CONCLUSIONS: STERP was associated with an elevated risk of sudden cardiac death
in a middle-aged population.
PMID- 27503849
TI - Prognostic Value of the Change in Heart Rate From the Supine to the Upright
Position in Patients With Chronic Heart Failure.
AB - BACKGROUND: The prognostic value of the change in heart rate from the supine to
upright position (?HR) in patients with chronic heart failure (HF) is unknown.
METHODS AND RESULTS: ?HR was measured in patients enrolled in the Trial of
Intensified Medical Therapy in Elderly Patients with Congestive Heart Failure
(TIME-CHF) who were in sinus rhythm and had no pacemaker throughout the trial
(n=321). The impact of ?HR on 18-month outcome (HF hospitalization-free survival)
was assessed. In addition, the prognostic effect of changes in ?HR between
baseline and month 6 on outcomes in the following 12 months was determined. A
lower ?HR was associated with a higher risk of death or HF hospitalization
(hazard ratio 1.79 [95% confidence interval {95% CI} 1.19-2.75] if ?HR <=3
beats/min [bpm], P=0.004). In the multivariate analysis, lower ?HR remained an
independent predictor of death or HF hospitalization (hazard ratio 1.75 [95% CI,
1.18-2.61] if ?HR <=3 bpm, P=0.004) along with ischemic HF etiology, lower
estimated glomerular filtration rate, presence and extent of rales, and no
baseline beta-blocker use. In patients without event during the first 6 months,
the change in ?HR from baseline to month 6 predicted death or HF hospitalization
during the following 12 months (hazard ratio=2.13 [95% CI 1.12-5.00] if rise in
?HR <2 bpm; P=0.027). CONCLUSIONS: ?HR as a simple bedside test is an independent
prognostic predictor in patients with chronic HF. ?HR is modifiable, and changes
in ?HR also provide prognostic information, which raises the possibility that ?HR
may help to guide treatment. CLINICAL TRIAL REGISTRATION INFORMATION: URL:
www.isrctn.org. Unique identifier: ISRCTN43596477.
PMID- 27503850
TI - Thrombin Generation and Atherothrombosis: What Does the Evidence Indicate?
PMID- 27503851
TI - Hemodynamic and Autonomic Response to Different Salt Intakes in Normotensive
Individuals.
AB - BACKGROUND: Even if sodium sensitivity represents a risk factor at any blood
pressure (BP) level, limited evidence is available that it may influence
cardiovascular control in normotensives, particularly in white individuals.
Therefore, the aim of the study was to investigate whether sodium sensitivity
alters hemodynamic or autonomic responses to salt in normotensives. METHODS AND
RESULTS: We evaluated the Sodium-Sensitivity Index (SS-Index) in 71 white
normotensives after 5 days of high- and low-sodium diets. We measured BP
continuously at the end of each period, estimating hemodynamic indices from BP
waveform analysis, and autonomic indices from heart rate (HR) and BP variability.
According to the SS-Index distribution, we defined 1 sodium-sensitive group (SS,
with SS-Index >15 mm Hg/[mmol.day]), 1 sodium-resistant group, (unresponsive to
sodium load with -15<= SS-Index <=+15), and 1 inverse sodium-sensitive group,
responsive to sodium by decreasing BP, with SS-Index <-15). We compared the
effects of the diets among groups, and correlated autonomic/hemodynamic indices
with the SS-Index. After sodium loading, a significant decrease in systemic
peripheral resistances, HR, spectral indices of BP modulation, and a significant
increase of indices of HR vagal modulation were found in the inverse sodium
sensitive group but not in SS normotensives. Moreover, the highest SS-Indices
were associated with the lesser vagal HR decelerations. CONCLUSIONS: Our data
suggest that salt sensitivity in white normotensive individuals is associated
with impaired vasodilation and altered autonomic response to dietary salt. Such
dysfunction may critically contribute to induce a BP response to dietary salt.
PMID- 27503852
TI - Vaccination knowledge, attitude and practice among Chinese travelers who visit
travel clinics in Preparation for international travel.
AB - BACKGROUND: Although international travel has become increasingly more common in
main land China, few data are available on vaccination knowledge, attitude and
practice (KAP) among Chinese travelers. METHOD: In each of 14 International
Travel Healthcare Centers (ITHCs) situated in mainland China 200 volunteers were
recruited for a cross-sectional investigation by questionnaire on KAP related to
travel vaccinations. For the evaluation the study subjects were grouped by
demographic data, past travel experience, travel destination, duration of stay
abroad, purpose of travel. RESULTS: Among the 2,800 Chinese travelers who
participated in the study, 67.1% were aware of national and travel vaccination
recommendations. The knowledge about vaccine preventable diseases was low. The
most common sources (73.4%) of information were requirements by destination
countries obtained in connection with the visa application, Chinese companies
employing workers/laborers for assignments overseas, and foreign schools. The
overall acceptance rate of recommended vaccines was 68.7%, but yellow fever was
accepted by 99.8% of the participants when recommended. Among 81.1% respondents
who recalled to have received vaccinations in the past, only 25.9% of them
brought the old vaccination records with them to their ITHC consultations.
CONCLUSION: The results indicate that increased awareness of the importance of
pre-travel vaccination is needed among the travellers in order to improve their
KAP.
PMID- 27503853
TI - Older age, chronic medical conditions and polypharmacy in Himalayan trekkers in
Nepal: an epidemiologic survey and case series.
AB - BACKGROUND: The number of tourists in Nepal doubled between 2003 and 2013 is
nearly 800 000. With the increased popularity of trekking, the number of those
with pre-existing medical conditions requiring access to healthcare is likely to
increase. We therefore sought to characterize the demographics and health status
of trekkers on the Everest Base Camp route in the Solukhumbu Valley. In addition,
we report cases that illustrate the potential complications of an ageing and
medicated population of trekkers with underlying diseases. METHODS: Trekkers over
18 years were enrolled in a larger observational cohort study on blood pressure
at high altitude at 2860 m. They answered a questionnaire regarding demographics,
medical history and current medications. Acute medical problems relating to
medication use that were brought to the attention of investigators were
documented and are presented as case reports. RESULTS: We enrolled 670 trekkers,
394 (59%) male, with a mean age of 48 years (range 18-76). Pre-existing medical
conditions were reported by 223 participants (33%). The most frequent conditions
included hypertension, hypercholesterolemia, migraines and thyroid dysfunction. A
total of 276 participants (41%) reported taking one or more medications. The most
common medications were acetazolamide (79, 12%), antihypertensives (50, 8%) and
NSAIDs (47, 7%), with 30 classes of drugs represented. Excluding acetazolamide,
older trekkers (age >50 years) were more likely than younger ones to take
medications (OR = 2.17; 95% CI 1.57-3.00; P <0.05). Acetazolamide use was not
related to age. CONCLUSIONS: Our findings illustrate a wide variety of medical
conditions present in trekkers in Nepal with wide-ranging potential complications
that could pose difficulties in areas where medical care is scarce and evacuation
difficult. Our cases illustrate the potential problems polypharmacy poses in
trekkers, and the need for local and expedition healthcare workers to be aware
of, and prepared for the common medical conditions present.
PMID- 27503854
TI - Use of antimicrobial agents for treatment and prevention of travellers' diarrhoea
in the face of enhanced risk of transient fecal carriage of multi-drug resistant
enterobacteriaceae: setting the stage for consensus recommendations.
AB - BACKGROUND: The recommendation that antibiotics should be used for routine
therapy of travellers' diarrhoea is being reconsidered in view of growing
evidence that the therapy may lead to intestinal carriage of multi-drug resistant
(MDR) colonic microbiota. This review attempts to put the issues of therapy and
MDR acquisition in perspective to help in the establishment of therapeutic
recommendations for travellers' diarrhoea. METHODS: The existing literature
showing the risk and consequences of acquisition of MDR microbiota in antibiotic
treated travellers was reviewed. Issues important to the development of firm
evidence-based recommendations for antibiotics use for treatment and prevention
of travellers' diarrhoea were researched. RESULTS: Six areas of research needed
to allow the development of evidence-based recommendations for antibiotic
treatment and -prevention of travellers' diarrhoea were identified. CONCLUSIONS:
Increasing worldwide occurrence of antibiotic resistance should alert public
health officials of the importance of encouraging local antibiotic stewardship
guidelines. Six areas to research are identified in this review to allow the
development of evidence-based recommendations for use of antibiotics for
treatment and selective prevention of travellers' diarrhoea. An interdisciplinary
ISTM Consensus group will consider the data available and develop current
recommendations for therapy and chemoprevention of travellers' diarrhoea
considering groups who would benefit the most from antimicrobials while
recognizing the hazards associated with broad use of these drugs. With interim
recommendations and ultimately evidence-based recommendations, guidelines can be
developed for management of travellers' diarrhoea considering populations and
destinations.
PMID- 27503855
TI - The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2
(GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from
the Cytoskeleton but Attenuated by Tissue Recruitment.
AB - Ligands with improved potency and selectivity for free fatty acid receptor 2
(FFA2R) have become available, and we here characterize the neutrophil responses
induced by one such agonist (Cmp1) and one antagonist (CATPB). Cmp1 triggered an
increase in the cytosolic concentration of Ca(2+), and the neutrophils were then
desensitized to Cmp1 and to acetate, a naturally occurring FFA2R agonist. The
antagonist CATPB selectively inhibited responses induced by Cmp1 or acetate. The
activated FFA2R induced superoxide anion secretion at a low level in naive blood
neutrophils. This response was largely increased by tumor necrosis factor alpha
(TNF-alpha) in a process associated with a recruitment of easily mobilizable
granules, but neutrophils recruited to an aseptic inflammation in vivo were
nonresponding. Superoxide production induced by Cmp1 was increased in latrunculin
A-treated neutrophils, but no reactivation of desensitized FFA2R was induced by
this drug, suggesting that the cytoskeleton is not directly involved in
terminating the response. The functional and regulatory differences between the
receptors that recognize short-chain fatty acids and formylated peptides,
respectively, imply different roles of these receptors in the orchestration of
inflammation and confirm the usefulness of a selective FFA2R agonist and
antagonist as tools for the exploration of the precise role of the FFA2R.
PMID- 27503856
TI - Unravelling the Mechanism of TrkA-Induced Cell Death by Macropinocytosis in
Medulloblastoma Daoy Cells.
AB - Macropinocytosis is a normal cellular process by which cells internalize
extracellular fluids and nutrients from their environment and is one strategy
that Ras-transformed pancreatic cancer cells use to increase uptake of amino
acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed
medulloblastoma brain tumors, we have shown that expression and activation of the
receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the
catastrophic disintegration of the cell membrane and in tumor cell death. The
molecular basis of this uncontrolled form of macropinocytosis has not been
previously understood. Here, we demonstrate that the overactivation of
macropinocytosis is caused by the simultaneous activation of two TrkA-mediated
pathways: (i) inhibition of RhoB via phosphorylation at Ser(185) by casein kinase
1, which relieves actin stress fibers, and (ii) FRS2-scaffolded Src and H-Ras
activation of RhoA, which stimulate actin reorganization and the formation of
lamellipodia. Since catastrophic macropinocytosis results in brain tumor cell
death, improved understanding of the mechanisms involved will facilitate future
efforts to reprogram tumors, even those resistant to apoptosis, to die.
PMID- 27503857
TI - SPRED1 Interferes with K-ras but Not H-ras Membrane Anchorage and Signaling.
AB - The Ras/mitogen-activated protein kinase (MAPK) signaling pathway is tightly
controlled by negative feedback regulators, such as the tumor suppressor SPRED1.
The SPRED1 gene also carries loss-of-function mutations in the RASopathy Legius
syndrome. Growth factor stimulation translocates SPRED1 to the plasma membrane,
triggering its inhibitory activity. However, it remains unclear whether SPRED1
there acts at the level of Ras or Raf. We show that pharmacological or galectin-1
(Gal-1)-mediated induction of B- and C-Raf-containing dimers translocates SPRED1
to the plasma membrane. This is facilitated in particular by SPRED1 interaction
with B-Raf and, via its N terminus, with Gal-1. The physiological significance of
these novel interactions is supported by two Legius syndrome-associated mutations
that show diminished binding to both Gal-1 and B-Raf. On the plasma membrane,
SPRED1 becomes enriched in acidic membrane domains to specifically perturb
membrane organization and extracellular signal-regulated kinase (ERK) signaling
of active K-ras4B (here, K-ras) but not H-ras. However, SPRED1 also blocks on the
nanoscale the positive effects of Gal-1 on H-ras. Therefore, a combinatorial
expression of SPRED1 and Gal-1 potentially regulates specific patterns of K-ras-
and H-ras-dependent signaling output. More broadly, our results open up the
possibility that related SPRED and Sprouty proteins act in a similar Ras and Raf
isoform-specific manner.
PMID- 27503858
TI - Association between home birth and breast feeding outcomes: a cross-sectional
study in 28 125 mother-infant pairs from Ireland and the UK.
AB - OBJECTIVES: To examine the association between breast feeding outcomes and place
of birth (home vs hospital birth). DESIGN: Population-based cross-sectional
study. SETTING: Ireland and UK. PARTICIPANTS: 10 604 mother-infant pairs from the
Growing Up in Ireland study (GUI, 2008-2009) and 17 521 pairs from the UK
Millennium Cohort Study (UKMCS, 2001-2002) at low risk of delivery complications
were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Breast
feeding initiation, exclusivity and duration. RESULTS: Home birth was found to be
significantly associated with breast feeding at all examined time points,
including at birth, 8 weeks, 6 months and breast feeding exclusively at 6 months.
In GUI, adjusted OR was 1.90 (95% CI 1.19 to 3.02), 1.78 (1.18 to 2.69), 1.85
(1.23 to 2.77) and 2.77 (1.78 to 4.33), respectively, and in UKMCS it was 2.49
(1.84 to 3.44), 2.49 (1.92 to 3.26), 2.90 (2.25 to 3.73) and 2.24 (1.14 to 4.03).
CONCLUSIONS: Home birth was strongly associated with improved breast feeding
outcomes in low-risk deliveries. While the association between home birth and
breast feeding is unlikely to be directly causal, further research is needed to
determine which factor(s) drive the observed differences, to facilitate
development of perinatal care that supports breast feeding.
PMID- 27503859
TI - Facilitating mental health research for patients, clinicians and researchers: a
mixed-method study.
AB - OBJECTIVES: Research registers using Consent for Contact (C4C) can facilitate
recruitment into mental health research studies, allowing investigators to
contact patients based on clinical records information. We investigated whether
such a register was useful for mental health research, seeking the perspectives
of patients and research investigators. SETTING AND DESIGN: In 2012, a C4C
register was developed in a large secondary mental health provider within the UK;
almost 9000 patients have joined. This mixed-method study audited the
effectiveness of the register. PARTICIPANTS: A 'mystery shopper' exercise was
conducted, and patients (n=21) were recruited to ask clinicians about the
availability of research opportunities. Structured interviews were conducted with
patients (n=52) about their experiences of being on the register. Similar
interviews were conducted with 18 investigators from 19 studies, who had
attempted to use the register to recruit participants. OUTCOME MEASURES: The
impact of C4C on study recruitment, and whether it helped patients learn about
research. RESULTS: So far, the register has provided 928 individuals with 1085
research opportunities (in 60% of cases, the individual agreed to participate in
the study). Clinicians were willing to link patients to research opportunities,
but often lacked information about studies. For patients, the register provided
opportunities which they may not otherwise have; 27 of 52 had participated in
studies since joining the register (18 participating for the first time). Most
investigators used the register to supplement recruitment to their studies, but
described problems in prescreening potential participants from a clinical record
for complex studies. CONCLUSIONS: Although the register helped investigators
recruit for studies, and provided patients with research opportunities,
clinicians' input is still useful for identifying suitable participants. C4C
registers should be adapted to provide clinicians with automatically updated
information on local studies allowing them to match patients on their caseload
with active studies.
PMID- 27503860
TI - Prospective, observational study comparing automated and visual point-of-care
urinalysis in general practice.
AB - OBJECTIVE: Point-of-care testing (POCT) urinalysis might reduce errors in
(subjective) reading, registration and communication of test results, and might
also improve diagnostic outcome and optimise patient management. Evidence is
lacking. In the present study, we have studied the analytical performance of
automated urinalysis and visual urinalysis compared with a reference standard in
routine general practice. SETTING: The study was performed in six general
practitioner (GP) group practices in the Netherlands. Automated urinalysis was
compared with visual urinalysis in these practices. Reference testing was
performed in a primary care laboratory (Saltro, Utrecht, The Netherlands).
PRIMARY AND SECONDARY OUTCOME MEASURES: Analytical performance of automated and
visual urinalysis compared with the reference laboratory method was the primary
outcome measure, analysed by calculating sensitivity, specificity, positive
predictive value (PPV) and negative predictive value (NPV) and Cohen's kappa
coefficient for agreement. Secondary outcome measure was the user-friendliness of
the POCT analyser. RESULTS: Automated urinalysis by experienced and routinely
trained practice assistants in general practice performs as good as visual
urinalysis for nitrite, leucocytes and erythrocytes. Agreement for nitrite is
high for automated and visual urinalysis. kappa's are 0.824 and 0.803 (ranked as
very good and good, respectively). Agreement with the central laboratory
reference standard for automated and visual urinalysis for leucocytes is rather
poor (0.256 for POCT and 0.197 for visual, respectively, ranked as fair and
poor). kappa's for erythrocytes are higher: 0.517 (automated) and 0.416 (visual),
both ranked as moderate. The Urisys 1100 analyser was easy to use and considered
to be not prone to flaws. CONCLUSIONS: Automated urinalysis performed as good as
traditional visual urinalysis on reading of nitrite, leucocytes and erythrocytes
in routine general practice. Implementation of automated urinalysis in general
practice is justified as automation is expected to reduce human errors in patient
identification and transcribing of results.
PMID- 27503861
TI - Association of volunteering with mental well-being: a lifecourse analysis of a
national population-based longitudinal study in the UK.
AB - OBJECTIVES: The association of volunteering with well-being has been found in
previous research, but mostly among older people. The aim of this study was to
examine the association of volunteering with mental well-being among the British
population across the life course. DESIGN: British Household Panel Survey, a
population-based longitudinal study. SETTING: UK. PARTICIPANTS: 66 343
observations (person-years). MAIN OUTCOME MEASURES: Mental well-being was
measured by using the General Health Questionnaire (GHQ-12 or GHQ); high values
denote high mental disorder. Four groups of volunteering participation were
created: frequent (once a week), infrequent (once a month/several times a year),
rare (once or less a year) and never. Multilevel linear models were used to
analyse variations in mental well-being over the life course by levels of
volunteering. RESULTS: When not considering age, those who engaged in
volunteering regularly appeared to experience higher levels of mental well-being
than those who never volunteered. To explore the association of volunteering with
the GHQ across the life course, interaction terms were fitted between age and
volunteering. The interactions were significant, demonstrating that these
associations vary by age. The association between volunteering and well-being did
not emerge during early adulthood to mid-adulthood, instead becoming apparent
above the age of 40 years and continuing up to old age. Moreover, in early
adulthood, the absence of engagement in voluntary activity was not related to
mental well-being, but GHQ scores for this group increased sharply with age,
levelling off after the age of 40 and then increasing again above the age of 70
years. The study also indicates variation in GHQ scores (65%) within individuals
across time, suggesting evidence of lifecourse effects. CONCLUSIONS: We conclude
that volunteering may be more meaningful for mental well-being at some points of
time in the life course.
PMID- 27503862
TI - Determinants of out-of-hours service users' potentially inappropriate referral or
non-referral to an emergency department: a retrospective cohort study in a local
health authority, Veneto Region, Italy.
AB - BACKGROUND: A growing presence of inappropriate patients has been recognised as
one of the main factors influencing emergency department (ED) overcrowding, which
is a very widespread problem all over the world. On the other hand, out-of-hours
(OOH) physicians must avoid delaying the diagnostic and therapeutic course of
patients with urgent medical conditions. The aim of this study was to analyse the
appropriateness of patient management by OOH services, in terms of their
potentially inappropriate referral or non-referral of non-emergency cases to the
ED. METHODS: This was an observational retrospective cohort study based on data
collected in 2011 by the local health authority No. 4 in the Veneto Region
(Italy). After distinguishing between patients contacting the OOH service who
were or were not referred to the ED, and checking for patients actually
presenting to the ED within 24 hours thereafter, these patients' medical
management was judged as potentially appropriate or inappropriate. RESULTS: The
analysis considered 22 662 OOH service contacts recorded in 2011. The cases of
potentially inappropriate non-referral to the ED were 392 (1.7% of all contacts),
as opposed to 1207 potentially inappropriate referrals (5.3% of all contacts).
Age, nationality, type of disease and type of intervention by the OOH service
were the main variables associated with the appropriateness of patient
management. CONCLUSIONS: These findings may be useful for pinpointing the factors
associated with a potentially inappropriate patient management by OOH services
and thus contribute to improving the deployment of healthcare and the quality of
care delivered by OOH services.
PMID- 27503863
TI - Scurvy and the enhancement of the senses.
PMID- 27503864
TI - Impact of pharmacist administration of influenza vaccines on uptake in Canada.
AB - BACKGROUND: Uptake of influenza vaccination in Canada remains suboptimal despite
widespread public funding. To increase access, several provinces have implemented
policies permitting pharmacists to administer influenza vaccines in community
pharmacies. We examined the impact of such policies on the uptake of seasonal
influenza vaccination in Canada. METHODS: We pooled data from the 2007-2014
cycles of the Canadian Community Health Survey (n = 481 526). To determine the
impact of influenza vaccine administration by pharmacists, we estimated the
prevalence ratio for the association between the presence of a pharmacist policy
and individual-level vaccine uptake using a modified Poisson regression model
(dependent variable: vaccine uptake) with normalized weights while controlling
for numerous health and sociodemographic factors. RESULTS: Across all survey
cycles combined, 28.8% of respondents reported receiving a seasonal influenza
vaccine during the 12 months before survey participation. Introduction of a
policy for pharmacist administration of influenza vaccine was associated with a
modest increase in coverage (2.2%) and an individual's likelihood of uptake
(adjusted prevalence ratio 1.05, 95% confidence interval 1.02-1.08).
INTERPRETATION: Uptake of influenza immunization was modestly increased in
Canadian jurisdictions that allowed pharmacists to administer influenza vaccines.
PMID- 27503865
TI - A 12-year-old girl with eczema not responding to treatment.
AB - A 12-year-old girl, who has had a history of intermittent skin rashes since
infancy, presents for the sixth time in four months for exacerbation of eczema
that is not responding to recommended treatment (daily baths, frequent
moisturization and twice-daily application of medium-potency topical
corticosteroids). Her parents express concern about the effect of her skin
disease on the child's life. They are worried about her sleeping difficulties and
decreased involvement in her regular activities; for example, she has stopped
playing sports and attending school. During the interview, the patient makes
minimal eye contact and appears agitated. Her medical history includes allergic
rhinitis. She looks systemically well, with normal temperature and vital signs.
Skin examination shows generalized xerotic skin and erythematous patches, with
predominantly flexural and facial excoriations affecting about half of the body.
There is no evidence of burrows, track marks, vesicular or pustular lesions, or
honey-coloured crusts. The rest of the exam is unremarkable.
PMID- 27503866
TI - Forming trust with vaccine fence-sitters.
PMID- 27503867
TI - Suicide rate higher for indigenous people in Labrador.
PMID- 27503868
TI - Why CMAJ writes editorials.
PMID- 27503869
TI - Thyroid nodules.
PMID- 27503870
TI - Taking action on the social determinants of health in clinical practice: a
framework for health professionals.
PMID- 27503871
TI - Acute coral contact dermatitis.
PMID- 27503872
TI - Psychotic disorders induced by antiepileptic drugs in people with epilepsy.
AB - Antiepileptic drug treatment can induce psychosis in some patients. However,
there are no agreed definitions or diagnostic criteria for antiepileptic drug
induced psychotic disorder in the classification systems of either epileptology
or psychiatry. In this study we investigated the clinical spectrum of
antiepileptic drug-induced psychotic disorder in patients with epilepsy. The
medical records of all patients with epilepsy who were diagnosed by a
neuropsychiatrist as having a psychotic disorder at the Royal Melbourne Hospital
from January 1993 to June 2015 were reviewed. Data were extracted regarding
epilepsy and its treatment, psychotic symptoms profile and outcome. The diagnosis
of epilepsy was established in accordance to the classification system of the
International League Against Epilepsy while that of psychotic disorder was made
according to the Diagnostic and Statistical Manual of Mental Disorders, 5th
Edition and the proposal on neuropsychiatric disorders in epilepsy. Patients with
antiepileptic drug-induced psychotic disorder were compared to those with
psychotic disorders unrelated to antiepileptic drugs assessed over the same
period (non-antiepileptic drug induced psychotic disorder group). Univariate
comparisons were performed and variables with a value of P < 0.1 were selected
for the multivariate logistic regression analysis. The records of 2630 in
patients and outpatients with epilepsy were screened, from which 98 (3.7%) with
psychotic disorders were identified. Among these, 14 (14.3%) were diagnosed to
have antiepileptic drug-induced psychotic disorder. Excluding one patient who
developed psychosis after valproate withdrawal, 76.9% in the antiepileptic drug
induced psychotic disorder group were female and the percentage of temporal lobe
involvement was higher in the antiepileptic drug induced psychotic disorder group
(69.2% versus 38.1%, P < 0.05). Current use of levetiracetam was higher in
antiepileptic drug-induced psychotic disorder group (84.6% versus 20.2%, P <
0.01) while use of carbamazepine was higher in the comparator group (15.4% versus
44.0%, P < 0.05). Multivariate logistic regression confirmed four factors
associated with antiepileptic drug-induced psychotic disorder: female gender,
temporal lobe involvement and use of levetiracetam, and a negative association
with carbamazepine. Disorganized behaviours and thinking were more common in the
antiepileptic drug-induced psychotic disorder group (100% versus 72.6% and 76.9%
versus 38.1%, respectively; P < 0.05). The percentage of continuous treatment
with antipsychotic drugs was lower in the antiepileptic drug-induced psychotic
disorder group (15.4% versus 66.7%, P < 0.01). No patients experienced a chronic
course in antiepileptic drug-induced psychotic disorder group whereas 40.5% did
in non-antiepileptic drug induced psychotic disorder (P < 0.05). Our findings
indicated that one in seven patients with epilepsy who developed psychosis had
antiepileptic drug-induced psychotic disorder. In these patients, female gender,
temporal lobe involvement and current use of levetiracetam were significantly
associated with antiepileptic drug induced psychotic disorder compared to other
types of psychosis, while carbamazepine had a negative association. Disorganized
behaviours and thinking were predominant in antiepileptic drug-induced psychotic
disorder. Patients with antiepileptic drug-induced psychotic disorder differed
from non-antiepileptic drug-induced psychotic disorders in having better outcome.
PMID- 27503873
TI - Sickle cell anemia mice develop a unique cardiomyopathy with restrictive
physiology.
AB - Cardiopulmonary complications are the leading cause of mortality in sickle cell
anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary
hypertension, diastolic, and autonomic dysfunction have all been described, but a
unifying pathophysiology and mechanism explaining the poor prognosis and
propensity to sudden death has been elusive. Herein, SCA mice underwent a
longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac
imaging with electrocardiography, histopathology, and molecular analysis to
determine the basis of cardiac dysfunction. We show that in SCA mice, anemia
induced hyperdynamic physiology was gradually superimposed with restrictive
physiology, characterized by progressive left atrial enlargement and diastolic
dysfunction with preserved systolic function. This phenomenon was absent in WT
mice with experimentally induced chronic anemia of similar degree and duration.
Restrictive physiology was associated with microscopic cardiomyocyte loss and
secondary fibrosis detectable as increased extracellular volume by cardiac-MRI.
Ultrastructural mitochondrial changes were consistent with severe chronic
hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome
analysis revealed up-regulation of genes involving angiogenesis, extracellular
matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel
transport and cardiac conduction were down-regulated. Indeed, progressive
corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA
mice before sudden death. Sudden cardiac death is common in humans with
restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide
a unifying cardiac pathophysiology that explains the reported cardiac
abnormalities and sudden death seen in humans with SCA.
PMID- 27503874
TI - Human striatal recordings reveal abnormal discharge of projection neurons in
Parkinson's disease.
AB - Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss
and aberrant striatal inputs into the basal ganglia network. However,
extrastriatal mechanisms have increasingly been the focus of attention, whereas
the status of striatal discharges in the parkinsonian human brain remains
conjectural. We now report the activity pattern of striatal projection neurons
(SPNs) in patients with PD undergoing deep brain stimulation surgery, compared
with patients with essential tremor (ET) and isolated dystonia (ID). The SPN
activity in ET was very low (2.1 +/- 0.1 Hz) and reminiscent of that found in
normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 +/-
1.2 Hz) and with abundant spike bursts. The difference between PD and ET was
reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and
normal nonhuman primates. The SPN activity was also increased in ID, but to a
lower level compared with the hyperactivity observed in PD. These results provide
direct evidence that the striatum contributes significantly altered signals to
the network in patients with PD.
PMID- 27503875
TI - FtsEX acts on FtsA to regulate divisome assembly and activity.
AB - Bacterial cell division is driven by the divisome, a ring-shaped protein complex
organized by the bacterial tubulin homolog FtsZ. Although most of the division
proteins in Escherichia coli have been identified, how they assemble into the
divisome and synthesize the septum remains poorly understood. Recent studies
suggest that the bacterial actin homolog FtsA plays a critical role in divisome
assembly and acts synergistically with the FtsQLB complex to regulate the
activity of the divisome. FtsEX, an ATP-binding cassette transporter-like
complex, is also necessary for divisome assembly and inhibits division when its
ATPase activity is inactivated. However, its role in division is not clear. Here,
we find that FtsEX acts on FtsA to regulate both divisome assembly and activity.
FtsX interacts with FtsA and this interaction is required for divisome assembly
and inhibition of divisome function by ATPase mutants of FtsEX. Our results
suggest that FtsEX antagonizes FtsA polymerization to promote divisome assembly
and the ATPase mutants of FtsEX block divisome activity by locking FtsA in the
inactive form or preventing FtsA from communicating with other divisome proteins.
Because FtsEX is known to govern cell wall hydrolysis at the septum, our findings
indicate that FtsEX acts on FtsA to promote divisome assembly and to coordinate
cell wall synthesis and hydrolysis at the septum. Furthermore, our study provides
evidence that FtsA mutants impaired for self-interaction are favored for
division, and FtsW plays a critical role in divisome activation in addition to
the FtsQLB complex.
PMID- 27503876
TI - Regulatory evolution of Tbx5 and the origin of paired appendages.
AB - The diversification of paired appendages has been a major factor in the
evolutionary radiation of vertebrates. Despite its importance, an understanding
of the origin of paired appendages has remained elusive. To address this problem,
we focused on T-box transcription factor 5 (Tbx5), a gene indispensable for
pectoral appendage initiation and development. Comparison of gene expression in
jawless and jawed vertebrates reveals that the Tbx5 expression in jawed
vertebrates is derived in having an expression domain that extends caudal to the
heart and gills. Chromatin profiling, phylogenetic footprinting, and functional
assays enabled the identification of a Tbx5 fin enhancer associated with this
apomorphic pattern of expression. Comparative functional analysis of reporter
constructs reveals that this enhancer activity is evolutionarily conserved among
jawed vertebrates and is able to rescue the finless phenotype of tbx5a mutant
zebrafish. Taking paleontological evidence of early vertebrates into account, our
results suggest that the gain of apomorphic patterns of Tbx5 expression and
regulation likely contributed to the morphological transition from a finless to
finned condition at the base of the vertebrate lineage.
PMID- 27503877
TI - Climate warming reduces fish production and benthic habitat in Lake Tanganyika,
one of the most biodiverse freshwater ecosystems.
AB - Warming climates are rapidly transforming lake ecosystems worldwide, but the
breadth of changes in tropical lakes is poorly documented. Sustainable management
of freshwater fisheries and biodiversity requires accounting for historical and
ongoing stressors such as climate change and harvest intensity. This is
problematic in tropical Africa, where records of ecosystem change are limited and
local populations rely heavily on lakes for nutrition. Here, using a ~1,500-y
paleoecological record, we show that declines in fishery species and endemic
molluscs began well before commercial fishing in Lake Tanganyika, Africa's
deepest and oldest lake. Paleoclimate and instrumental records demonstrate
sustained warming in this lake during the last ~150 y, which affects biota by
strengthening and shallowing stratification of the water column. Reductions in
lake mixing have depressed algal production and shrunk the oxygenated benthic
habitat by 38% in our study areas, yielding fish and mollusc declines. Late-20th
century fish fossil abundances at two of three sites were lower than at any other
time in the last millennium and fell in concert with reduced diatom abundance and
warming water. A negative correlation between lake temperature and fish and
mollusc fossils over the last ~500 y indicates that climate warming and
intensifying stratification have almost certainly reduced potential fishery
production, helping to explain ongoing declines in fish catches. Long-term
declines of both benthic and pelagic species underscore the urgency of strategic
efforts to sustain Lake Tanganyika's extraordinary biodiversity and ecosystem
services.
PMID- 27503878
TI - Early emerging system for reasoning about the social nature of food.
AB - Selecting appropriate foods is a complex and evolutionarily ancient problem, yet
past studies have revealed little evidence of adaptations present in infancy that
support sophisticated reasoning about perceptual properties of food. We propose
that humans have an early-emerging system for reasoning about the social nature
of food selection. Specifically, infants' reasoning about food choice is tied to
their thinking about agents' intentions and social relationships. Whereas infants
do not expect people to like the same objects, infants view food preferences as
meaningfully shared across individuals. Infants' reasoning about food preferences
is fundamentally social: They generalize food preferences across individuals who
affiliate, or who speak a common language, but not across individuals who
socially disengage or who speak different languages. Importantly, infants'
reasoning about food preferences is flexibly calibrated to their own experiences:
Tests of bilingual babies reveal that an infant's sociolinguistic background
influences whether she will constrain her generalization of food preferences to
people who speak the same language. Additionally, infants' systems for reasoning
about food is differentially responsive to positive and negative information.
Infants generalize information about food disgust across all people, regardless
of those people's social identities. Thus, whereas food preferences are seen as
embedded within social groups, disgust is interpreted as socially universal,
which could help infants avoid potentially dangerous foods. These studies reveal
an early-emerging system for thinking about food that incorporates social
reasoning about agents and their relationships, and allows infants to make
abstract, flexible, adaptive inferences to interpret others' food choices.
PMID- 27503879
TI - Correction for Eklund et al., Cluster failure: Why fMRI inferences for spatial
extent have inflated false-positive rates.
PMID- 27503880
TI - Increased water deficit decreases Douglas fir growth throughout western US
forests.
AB - Changes in tree growth rates can affect tree mortality and forest feedbacks to
the global carbon cycle. As air temperature increases, evaporative demand also
increases, increasing effective drought in forest ecosystems. Using a spatially
comprehensive network of Douglas fir (Pseudotsuga menziesii) chronologies from
122 locations that represent distinct climate environments in the western United
States, we show that increased temperature decreases growth via vapor pressure
deficit (VPD) across all latitudes. Using an ensemble of global circulation
models, we project an increase in both the mean VPD associated with the lowest
growth extremes and the probability of exceeding these VPD values. As temperature
continues to increase in future decades, we can expect deficit-related stress to
increase and consequently Douglas fir growth to decrease throughout its US range.
PMID- 27503881
TI - No relative expansion of the number of prefrontal neurons in primate and human
evolution.
AB - Human evolution is widely thought to have involved a particular expansion of
prefrontal cortex. This popular notion has recently been challenged, although
controversies remain. Here we show that the prefrontal region of both human and
nonhuman primates holds about 8% of cortical neurons, with no clear difference
across humans and other primates in the distribution of cortical neurons or white
matter cells along the anteroposterior axis. Further, we find that the volumes of
human prefrontal gray and white matter match the expected volumes for the number
of neurons in the gray matter and for the number of other cells in the white
matter compared with other primate species. These results indicate that
prefrontal cortical expansion in human evolution happened along the same
allometric trajectory as for other primate species, without modification of the
distribution of neurons across its surface or of the volume of the underlying
white matter. We thus propose that the most distinctive feature of the human
prefrontal cortex is its absolute number of neurons, not its relative volume.
PMID- 27503882
TI - Climate influence on Vibrio and associated human diseases during the past half
century in the coastal North Atlantic.
AB - Climate change is having a dramatic impact on marine animal and plant communities
but little is known of its influence on marine prokaryotes, which represent the
largest living biomass in the world oceans and play a fundamental role in
maintaining life on our planet. In this study, for the first time to our
knowledge, experimental evidence is provided on the link between multidecadal
climatic variability in the temperate North Atlantic and the presence and spread
of an important group of marine prokaryotes, the vibrios, which are responsible
for several infections in both humans and animals. Using archived formalin
preserved plankton samples collected by the Continuous Plankton Recorder survey
over the past half-century (1958-2011), we assessed retrospectively the relative
abundance of vibrios, including human pathogens, in nine areas of the North
Atlantic and North Sea and showed correlation with climate and plankton changes.
Generalized additive models revealed that long-term increase in Vibrio abundance
is promoted by increasing sea surface temperatures (up to ~1.5 degrees C over
the past 54 y) and is positively correlated with the Northern Hemisphere
Temperature (NHT) and Atlantic Multidecadal Oscillation (AMO) climatic indices (P
< 0.001). Such increases are associated with an unprecedented occurrence of
environmentally acquired Vibrio infections in the human population of Northern
Europe and the Atlantic coast of the United States in recent years.
PMID- 27503883
TI - Belowground rhizomes in paleosols: The hidden half of an Early Devonian vascular
plant.
AB - The colonization of terrestrial environments by rooted vascular plants had far
reaching impacts on the Earth system. However, the belowground structures of
early vascular plants are rarely documented, and thus the plant-soil interactions
in early terrestrial ecosystems are poorly understood. Here we report the
earliest rooted paleosols (fossil soils) in Asia from Early Devonian deposits of
Yunnan, China. Plant traces are extensive within the soil and occur as complex
network-like structures, which are interpreted as representing long-lived,
belowground rhizomes of the basal lycopsid Drepanophycus The rhizomes produced
large clones and helped the plant survive frequent sediment burial in well
drained soils within a seasonal wet-dry climate zone. Rhizome networks
contributed to the accumulation and pedogenesis of floodplain sediments and
increased the soil stabilizing effects of early plants. Predating the appearance
of trees with deep roots in the Middle Devonian, plant rhizomes have long
functioned in the belowground soil ecosystem. This study presents strong, direct
evidence for plant-soil interactions at an early stage of vascular plant
radiation. Soil stabilization by complex rhizome systems was apparently
widespread, and contributed to landscape modification at an earlier time than had
been appreciated.
PMID- 27503884
TI - DNA damage checkpoint kinase ATM regulates germination and maintains genome
stability in seeds.
AB - Genome integrity is crucial for cellular survival and the faithful transmission
of genetic information. The eukaryotic cellular response to DNA damage is
orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED
(ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological
roles for these sensor kinases in control of seed germination. We demonstrate
that double-strand breaks (DSBs) are rate-limiting for germination. We identify
that desiccation tolerant seeds exhibit a striking transcriptional DSB damage
response during germination, indicative of high levels of genotoxic stress, which
is induced following maturation drying and quiescence. Mutant atr and atm seeds
are highly resistant to aging, establishing ATM and ATR as determinants of seed
viability. In response to aging, ATM delays germination, whereas atm mutant seeds
germinate with extensive chromosomal abnormalities. This identifies ATM as a
major factor that controls germination in aged seeds, integrating progression
through germination with surveillance of genome integrity. Mechanistically, ATM
functions through control of DNA replication in imbibing seeds. ATM signaling is
mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED
5, an essential factor required for the aging-induced delay to germination. In
the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR,
with changes in dormancy and germination potential modulated by environmental
signals, including temperature and soil moisture. Collectively, our findings
reveal physiological functions for these sensor kinases in linking genome
integrity to germination, thereby influencing seed quality, crucial for plant
survival in the natural environment and sustainable crop production.
PMID- 27503885
TI - Secondary expansion of the transient subplate zone in the developing cerebrum of
human and nonhuman primates.
AB - The subplate (SP) was the last cellular compartment added to the Boulder
Committee's list of transient embryonic zones [Bystron I, Blakemore C, Rakic P
(2008) Nature Rev Neurosci 9(2):110-122]. It is highly developed in human and
nonhuman primates, but its origin, mode, and dynamics of development, resolution,
and eventual extinction are not well understood because human postmortem tissue
offers only static descriptive data, and mice cannot serve as an adequate
experimental model for the distinct regional differences in primates. Here, we
take advantage of the large and slowly developing SP in macaque monkey to examine
the origin, settling pattern, and subsequent dispersion of the SP neurons in
primates. Monkey embryos exposed to the radioactive DNA replication marker
tritiated thymidine ([(3)H]dT, or TdR) at early embryonic ages were killed at
different intervals postinjection to follow postmitotic cells' positional
changes. As expected in primates, most SP neurons generated in the ventricular
zone initially migrate radially, together with prospective layer 6 neurons.
Surprisingly, mostly during midgestation, SP cells become secondarily displaced
and widespread into the expanding SP zone, which becomes particularly wide
subjacent to the association cortical areas and underneath the summit of its
folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and
corticocortical axons is mainly responsible for this region-dependent passive
dispersion of the SP cells. Histologic and immunohistochemical comparison with
the human SP at corresponding fetal ages indicates that the same developmental
events occur in both primate species.
PMID- 27503886
TI - Adiabatic quenches and characterization of amplitude excitations in a continuous
quantum phase transition.
AB - Spontaneous symmetry breaking occurs in a physical system whenever the ground
state does not share the symmetry of the underlying theory, e.g., the
Hamiltonian. This mechanism gives rise to massless Nambu-Goldstone modes and
massive Anderson-Higgs modes. These modes provide a fundamental understanding of
matter in the Universe and appear as collective phase or amplitude excitations of
an order parameter in a many-body system. The amplitude excitation plays a
crucial role in determining the critical exponents governing universal
nonequilibrium dynamics in the Kibble-Zurek mechanism (KZM). Here, we
characterize the amplitude excitations in a spin-1 condensate and measure the
energy gap for different phases of the quantum phase transition. At the quantum
critical point of the transition, finite-size effects lead to a nonzero gap. Our
measurements are consistent with this prediction, and furthermore, we demonstrate
an adiabatic quench through the phase transition, which is forbidden at the mean
field level. This work paves the way toward generating entanglement through an
adiabatic phase transition.
PMID- 27503887
TI - Atom-scale depth localization of biologically important chemical elements in
molecular layers.
AB - In nature, biomolecules are often organized as functional thin layers in
interfacial architectures, the most prominent examples being biological
membranes. Biomolecular layers play also important roles in context with
biotechnological surfaces, for instance, when they are the result of adsorption
processes. For the understanding of many biological or biotechnologically
relevant phenomena, detailed structural insight into the involved biomolecular
layers is required. Here, we use standing-wave X-ray fluorescence (SWXF) to
localize chemical elements in solid-supported lipid and protein layers with near
Angstrom precision. The technique complements traditional specular reflectometry
experiments that merely yield the layers' global density profiles. While earlier
work mostly focused on relatively heavy elements, typically metal ions, we show
that it is also possible to determine the position of the comparatively light
elements S and P, which are found in the most abundant classes of biomolecules
and are therefore particularly important. With that, we overcome the need of
artificial heavy atom labels, the main obstacle to a broader application of high
resolution SWXF in the fields of biology and soft matter. This work may thus
constitute the basis for the label-free, element-specific structural
investigation of complex biomolecular layers and biological surfaces.
PMID- 27503888
TI - Time-resolved 2-million-year-old supernova activity discovered in Earth's
microfossil record.
AB - Massive stars ([Formula: see text]), which terminate their evolution as core
collapse supernovae, are theoretically predicted to eject [Formula: see text] of
the radioisotope (60)Fe (half-life 2.61 Ma). If such an event occurs sufficiently
close to our solar system, traces of the supernova debris could be deposited on
Earth. Herein, we report a time-resolved (60)Fe signal residing, at least
partially, in a biogenic reservoir. Using accelerator mass spectrometry, this
signal was found through the direct detection of live (60)Fe atoms contained
within secondary iron oxides, among which are magnetofossils, the fossilized
chains of magnetite crystals produced by magnetotactic bacteria. The
magnetofossils were chemically extracted from two Pacific Ocean sediment drill
cores. Our results show that the (60)Fe signal onset occurs around 2.6 Ma to 2.8
Ma, near the lower Pleistocene boundary, terminates around 1.7 Ma, and peaks at
about 2.2 Ma.
PMID- 27503889
TI - Ab initio molecular dynamics of solvation effects on reactivity at electrified
interfaces.
AB - Using ab initio molecular dynamics as implemented in periodic, self-consistent
(generalized gradient approximation Perdew-Burke-Ernzerhof) density functional
theory, we investigated the mechanism of methanol electrooxidation on Pt(111). We
investigated the role of water solvation and electrode potential on the
energetics of the first proton transfer step, methanol electrooxidation to
methoxy (CH3O) or hydroxymethyl (CH2OH). The results show that solvation weakens
the adsorption of methoxy to uncharged Pt(111), whereas the binding energies of
methanol and hydroxymethyl are not significantly affected. The free energies of
activation for breaking the C-H and O-H bonds in methanol were calculated through
a Blue Moon Ensemble using constrained ab initio molecular dynamics. Calculated
barriers for these elementary steps on unsolvated, uncharged Pt(111) are similar
to results for climbing-image nudged elastic band calculations from the
literature. Water solvation reduces the barriers for both C-H and O-H bond
activation steps with respect to their vapor-phase values, although the effect is
more pronounced for C-H bond activation, due to less disruption of the hydrogen
bond network. The calculated activation energy barriers show that breaking the C
H bond of methanol is more facile than the O-H bond on solvated negatively biased
or uncharged Pt(111). However, with positive bias, O-H bond activation is
enhanced, becoming slightly more facile than C-H bond activation.
PMID- 27503890
TI - Derepression of hTERT gene expression promotes escape from oncogene-induced
cellular senescence.
AB - Oncogene-induced senescence (OIS) is a critical tumor-suppressing mechanism that
restrains cancer progression at premalignant stages, in part by causing telomere
dysfunction. Currently it is unknown whether this proliferative arrest presents a
stable and therefore irreversible barrier to cancer progression. Here we
demonstrate that cells frequently escape OIS induced by oncogenic H-Ras and B
Raf, after a prolonged period in the senescence arrested state. Cells that had
escaped senescence displayed high oncogene expression levels, retained functional
DNA damage responses, and acquired chromatin changes that promoted c-Myc
dependent expression of the human telomerase reverse transcriptase gene (hTERT).
Telomerase was able to resolve existing telomeric DNA damage response foci and
suppressed formation of new ones that were generated as a consequence of DNA
replication stress and oncogenic signals. Inhibition of MAP kinase signaling,
suppressing c-Myc expression, or inhibiting telomerase activity, caused telomere
dysfunction and proliferative defects in cells that had escaped senescence,
whereas ectopic expression of hTERT facilitated OIS escape. In human early
neoplastic skin and breast tissue, hTERT expression was detected in cells that
displayed features of senescence, suggesting that reactivation of telomerase
expression in senescent cells is an early event during cancer progression in
humans. Together, our data demonstrate that cells arrested in OIS retain the
potential to escape senescence by mechanisms that involve derepression of hTERT
expression.
PMID- 27503891
TI - Differential lipid binding of vinculin isoforms promotes quasi-equivalent
dimerization.
AB - The main cause of death globally remains debilitating heart conditions, such as
dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), which are
often due to mutations of specific components of adhesion complexes. Vinculin
regulates these complexes and plays essential roles in intercalated discs that
are necessary for muscle cell function and coordinated movement and in the
development and function of the heart. Humans bearing familial or sporadic
mutations in vinculin suffer from chronic, progressively debilitating DCM that
ultimately leads to cardiac failure and death, whereas autosomal dominant
mutations in vinculin can also provoke HCM, causing acute cardiac failure. The
DCM/HCM-associated mutants of vinculin occur in the 68-residue insert unique to
the muscle-specific, alternatively spliced isoform of vinculin, termed
metavinculin (MV). Contrary to studies that suggested that phosphoinositol-4,5
bisphosphate (PIP2) only induces vinculin homodimers, which are asymmetric, we
show that phospholipid binding results in a domain-swapped symmetric MV dimer via
a quasi-equivalent interface compared with vinculin involving R975. Although one
of the two PIP2 binding sites is preserved, the symmetric MV dimer that bridges
two PIP2 molecules differs from the asymmetric vinculin dimer that bridges only
one PIP2 Unlike vinculin, wild-type MV and the DCM/HCM-associated R975W mutant
bind PIP2 in their inactive conformations, and R975W MV fails to dimerize.
Mutating selective vinculin residues to their corresponding MV residues, or vice
versa, switches the isoform's dimeric constellation and lipid binding site.
Collectively, our data suggest that MV homodimerization modulates microfilament
attachment at muscular adhesion sites and furthers our understanding of MV
mediated cardiac remodeling.
PMID- 27503892
TI - Functional neuroanatomy of intuitive physical inference.
AB - To engage with the world-to understand the scene in front of us, plan actions,
and predict what will happen next-we must have an intuitive grasp of the world's
physical structure and dynamics. How do the objects in front of us rest on and
support each other, how much force would be required to move them, and how will
they behave when they fall, roll, or collide? Despite the centrality of physical
inferences in daily life, little is known about the brain mechanisms recruited to
interpret the physical structure of a scene and predict how physical events will
unfold. Here, in a series of fMRI experiments, we identified a set of cortical
regions that are selectively engaged when people watch and predict the unfolding
of physical events-a "physics engine" in the brain. These brain regions are
selective to physical inferences relative to nonphysical but otherwise highly
similar scenes and tasks. However, these regions are not exclusively engaged in
physical inferences per se or, indeed, even in scene understanding; they overlap
with the domain-general "multiple demand" system, especially the parts of that
system involved in action planning and tool use, pointing to a close relationship
between the cognitive and neural mechanisms involved in parsing the physical
content of a scene and preparing an appropriate action.
PMID- 27503893
TI - Xkr8 phospholipid scrambling complex in apoptotic phosphatidylserine exposure.
AB - Xk-related protein (Xkr) 8, a protein carrying 10 transmembrane regions, is
essential for scrambling phospholipids during apoptosis. Here, we found Xkr8 as a
complex with basigin (BSG) or neuroplastin (NPTN), type I membrane proteins in
the Ig superfamily. In BSG(-/-)NPTN(-/-) cells, Xkr8 localized intracellularly,
and the apoptosis stimuli failed to expose phosphatidylserine, indicating that
BSG and NPTN chaperone Xkr8 to the plasma membrane to execute its scrambling
activity. Mutational analyses of BSG showed that the atypical glutamic acid in
the transmembrane region is required for BSG's association with Xkr8. In cells
exposed to apoptotic signals, Xkr8 was cleaved at the C terminus and the Xkr8/BSG
complex formed a higher-order complex, likely to be a heterotetramer consisting
of two molecules of Xkr8 and two molecules of BSG or NPTN, suggesting that this
cleavage causes the formation of a larger complex of Xkr8-BSG/NPTN for
phospholipid scrambling.
PMID- 27503894
TI - Salmonella Typhimurium utilizes a T6SS-mediated antibacterial weapon to establish
in the host gut.
AB - The mammalian gastrointestinal tract is colonized by a high-density polymicrobial
community where bacteria compete for niches and resources. One key competition
strategy includes cell contact-dependent mechanisms of interbacterial antagonism,
such as the type VI secretion system (T6SS), a multiprotein needle-like apparatus
that injects effector proteins into prokaryotic and/or eukaryotic target cells.
However, the contribution of T6SS antibacterial activity during pathogen invasion
of the gut has not been demonstrated. We report that successful establishment in
the gut by the enteropathogenic bacterium Salmonella enterica serovar Typhimurium
requires a T6SS encoded within Salmonella pathogenicity island-6 (SPI-6). In an
in vitro setting, we demonstrate that bile salts increase SPI-6 antibacterial
activity and that S Typhimurium kills commensal bacteria in a T6SS-dependent
manner. Furthermore, we provide evidence that one of the two T6SS nanotube
subunits, Hcp1, is required for killing Klebsiella oxytoca in vitro and that this
activity is mediated by the specific interaction of Hcp1 with the antibacterial
amidase Tae4. Finally, we show that K. oxytoca is killed in the host gut in an
Hcp1-dependent manner and that the T6SS antibacterial activity is essential for
Salmonella to establish infection within the host gut. Our findings provide an
example of pathogen T6SS-dependent killing of commensal bacteria as a mechanism
to successfully colonize the host gut.
PMID- 27503895
TI - miR-579-3p controls melanoma progression and resistance to target therapy.
AB - Therapy of melanoma patients harboring activating mutations in the BRAF (V-raf
murine sarcoma viral oncogene homolog B1) oncogene with a combination of BRAF and
MEK inhibitors is plagued by the development of drug resistance. Mutational
events, as well as adaptive mechanisms, contribute to the development of drug
resistance. In this context we uncover here the role of a miRNA, miR-579-3p. We
first show that low expression of miR-579-3p is a negative prognostic factor
correlating with poor survival. Expression levels of miR-579-3p decrease from
nevi to stage III/IV melanoma samples and even further in cell lines resistant to
BRAF/MEK inhibitors. Mechanistically, we demonstrate that miR-579-3p acts as an
oncosuppressor by targeting the 3'UTR of two oncoproteins: BRAF and an E3
ubiquitin protein ligase, MDM2. Moreover miR-579-3p ectopic expression impairs
the establishment of drug resistance in human melanoma cells. Finally, miR-579-3p
is strongly down-regulated in matched tumor samples from patients before and
after the development of resistance to targeted therapies.
PMID- 27503896
TI - Specificity of Protein Covalent Modification by the Electrophilic Proteasome
Inhibitor Carfilzomib in Human Cells.
AB - Carfilzomib (CFZ) is a second-generation proteasome inhibitor that is Food and
Drug Administration and European Commission approved for the treatment of
relapsed or refractory multiple myeloma. CFZ is an epoxomicin derivative with an
epoxyketone electrophilic warhead that irreversibly adducts the catalytic
threonine residue of the beta5 subunit of the proteasome. Although CFZ produces a
highly potent, sustained inactivation of the proteasome, the electrophilic nature
of the drug could potentially produce off-target protein adduction. To address
this possibility, we synthesized an alkynyl analog of CFZ and investigated
protein adduction by this analog in HepG2 cells. Using click chemistry coupled
with streptavidin based IP and shotgun tandem mass spectrometry (MS/MS), we
identified two off-target proteins, cytochrome P450 27A1 (CYP27A1) and
glutathione S-transferase omega 1 (GSTO1), as targets of the alkynyl CFZ probe.
We confirmed the adduction of CYP27A1 and GSTO1 by streptavidin capture and
immunoblotting methodology and then site-specifically mapped the adducts with
targeted MS/MS methods. Although CFZ adduction of CYP27A1 and GSTO1 in vitro
decreased the activities of these enzymes, the small fraction of these proteins
modified by CFZ in intact cells should limit the impact of these off-target
modifications. The data support the high selectivity of CFZ for covalent
modification of its therapeutic targets, despite the presence of a reactive
electrophile. The approach we describe offers a generalizable method to evaluate
the safety profile of covalent protein-modifying therapeutics.
PMID- 27503898
TI - Changing undergraduate human anatomy and physiology laboratories: perspectives
from a large-enrollment course.
AB - In the present article, a veteran lecturer of human anatomy and physiology taught
several sections of the laboratory component for the first time and shares his
observations and analysis from this unique perspective. The article discusses a
large-enrollment, content-heavy anatomy and physiology course in relationship to
published studies on learning and student self-efficacy. Changes in the
laboratory component that could increase student learning are proposed. The
author also points out the need for research to assess whether selective
curricular changes could increase the depth of understanding and retention of
learned material.
PMID- 27503897
TI - Human Sirtuin 2 Localization, Transient Interactions, and Impact on the Proteome
Point to Its Role in Intracellular Trafficking.
AB - Human sirtuin 2 (SIRT2) is an NAD+-dependent deacetylase that primarily functions
in the cytoplasm, where it can regulate alpha-tubulin acetylation levels. SIRT2
is linked to cancer progression, neurodegeneration, and infection with bacteria
or viruses. However, the current knowledge about its interactions and the means
through which it exerts its functions has remained limited. Here, we aimed to
gain a better understanding of its cellular functions by characterizing SIRT2
subcellular localization, the identity and relative stability of its protein
interactions, and its impact on the proteome of primary human fibroblasts. To
assess the relative stability of SIRT2 interactions, we used immunoaffinity
purification in conjunction with both label-free and metabolic labeling
quantitative mass spectrometry. In addition to the expected associations with
cytoskeleton proteins, including its known substrate TUBA1A, our results reveal
that SIRT2 specifically interacts with proteins functioning in membrane
trafficking, secretory processes, and transcriptional regulation. By quantifying
their relative stability, we found most interactions to be transient, indicating
a dynamic SIRT2 environment. We discover that SIRT2 localizes to the ER-Golgi
intermediate compartment (ERGIC), and that this recruitment requires an intact ER
Golgi trafficking pathway. Further expanding these findings, we used microscopy
and interaction assays to establish the interaction and coregulation of SIRT2
with liprin-beta1 scaffolding protein (PPFiBP1), a protein with roles in focal
adhesions disassembly. As SIRT2 functions may be accomplished via interactions,
enzymatic activity, and transcriptional regulation, we next assessed the impact
of SIRT2 levels on the cellular proteome. SIRT2 knockdown led to changes in the
levels of proteins functioning in membrane trafficking, including some of its
interaction partners. Altogether, our study expands the knowledge of SIRT2
cytoplasmic functions to define a previously unrecognized involvement in
intracellular trafficking pathways, which may contribute to its roles in cellular
homeostasis and human diseases.
PMID- 27503899
TI - A method of providing engaging formative feedback to large cohort first-year
physiology and anatomy students.
AB - A growing body of evidence demonstrates a critical role for effective, meaningful
feedback to enhance student learning. Effective feedback can become part of the
learning cycle that is not only a learning opportunity for the student but can
also be used to inform the teacher and ongoing curriculum development. Feedback
is considered particularly important during the first year of university and can
even be viewed as a retention strategy that can help attenuate student
performance anxieties and solidify perceptions of academic support.
Unfortunately, the provision of individualized, timely feedback can be
particularly challenging in first-year courses as they tend to be large and
diverse cohort classes that pose challenges of time and logistics. Various forms
of generic feedback can provide rapid and cost-effect feedback to large cohorts
but may be of limited benefit to students other than signaling weaknesses in
knowledge. The present study describes a method that was used to provide
formative task-related feedback to a large cohort of first-year physiology and
anatomy students. Based on student evaluations presented in this study, this
method provided feedback in a manner that engaged students, uncovered underlying
misconceptions, facilitated peer discussion, and provided opportunity for new
instruction while allowing the lecturer to recognize common gaps in knowledge and
inform ongoing curriculum development.
PMID- 27503900
TI - Engaging medical undergraduates in question making: a novel way to reinforcing
learning in physiology.
AB - The monotony of conventional didactic lectures makes students less attentive
toward learning, and they tend to memorize isolated facts without understanding,
just for the sake of passing exams. Therefore, to promote a habit of gaining
indepth knowledge of basic sciences in medical undergraduates along with honing
of their communication and analytical skills, we introduced this more interactive
way of learning. The present study was performed on 99 first-semester medical
students. After conventional didactic lectures, students were asked to prepare
small conceptual questions on the topic. They were divided into two teams, which
were made to ask questions to each other. If a team failed to answer, the student
who questioned was supposed to answer to the satisfaction of the other team's
student. Data were then obtained by getting feedback from the students on a 10
item questionnaire, and statistical evaluation was done using MS Excel and SPSS.
To draft questions, students went through the whole system comprehensively and
made questions from every possible aspect of the topic. Some of the questions
(30%) were of recall type, but most judged higher cognitive domains. Student
feedback revealed that they were satisfied, motivated to read more, and were
confident of applying this learning and communication skills in future clinical
practice. Students also expressed their desire to implement this activity as a
regular feature of the curriculum. The activity resulted in an increase in
student perceptions of their knowledge on the topic as well as communicative and
analytical skills. This may eventually lead to better learning.
PMID- 27503901
TI - Electrophysiology for biomedical engineering students: a practical and
theoretical course in animal electrocorticography.
AB - The major challenge in laboratory teaching is the application of abstract
concepts in simple and direct practical lessons. However, students rarely have
the opportunity to participate in a laboratory that combines practical learning
with a realistic research experience. In the Biomedical Engineering career, we
offer short and optional courses to complement studies for students as they
initiate their Graduation Project. The objective of these theoretical and
practical courses is to introduce students to the topics of their projects. The
present work describes an experience in electrophysiology to teach undergraduate
students how to extract cortical information using electrocorticographic
techniques. Students actively participate in some parts of the experience and
then process and analyze the data obtained with different signal processing
tools. In postlaboratory evaluations, students described the course as an
exceptional opportunity for students interested in following a postgraduate
science program and fully appreciated their contents.
PMID- 27503902
TI - Cold pressor test using strain-gauge plethysmography.
AB - This laboratory activity is designed to teach students how to measure forearm
muscle blood flow (FBF) to describe the mechanisms of peripheral blood flow
thermal regulation in healthy subjects. The cold pressor test (CPT) is the
clinical procedure used in the experiment to induce arterial vasoconstriction.
Strain-gauge plethysmography is applied on the patient's forearm to noninvasive
monitor vasoconstriction effects on local blood perfusion and physiological
parameters such as blood pressure (BP) and heart rate (HR). Patients with an
altered peripheral vascular resistance (e.g., in hypertension) have different
responses to the CPT from healthy subjects. To date, experimental evidence
remains unexplained, as we do not know if the BP and HR increase is caused by a
decrease in flow rate or an increase in peripheral vascular resistance during the
test. To clarify this situation, we have to quantify the parameter we assume is
being conditioned by the regulatory physiological intervention, i.e., peripheral
vascular resistance. Peripheral vascular resistance quantification can be
calculated as the ratio between muscle flow and mean arterial pressure. Students
will learn how to apply the instrumental procedure to collect and analyze data
before, during, and after the CPT and to describe the physiological responses of
the peripheral vascular system to external stressors. They will also learn how to
distinguish healthy from pathological responses on the basis of how sympathetic
nervous system reactions influence the biomechanics of peripheral vessels.
PMID- 27503903
TI - The brain robot "Herr Tie": discovering basic principles of brain function at
primary school.
PMID- 27503904
TI - Perceptions of undergraduate students on the use of animals in practical classes.
PMID- 27503905
TI - Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate
in relapsing-remitting multiple sclerosis patients: 3-year results of the
Glatiramer Acetate Low-Frequency Administration open-label extension study.
AB - BACKGROUND: The 1-year placebo-controlled (PC) phase of the Glatiramer Acetate
Low-Frequency Administration (GALA) study showed that glatiramer acetate 40 mg/mL
three times weekly (GA40) significantly reduced annualized relapse rate (ARR) and
magnetic resonance imaging (MRI) activity in patients with relapsing-remitting
multiple sclerosis. Patients completing the PC phase were invited to an open
label (OL) extension. OBJECTIVE: To evaluate the effects of early start (ES) and
delayed start (DS) of GA40 over 3 years. METHODS: A total of 97.2% of patients
completing the PC phase received GA40 in the OL extension. ES ( n = 943) patients
received GA40 throughout; DS ( n = 461) patients received placebo during the PC
phase and GA40 during the OL phase. Relapse, MRI, disease progression, and safety
were evaluated. RESULTS: A total of 1041 patients completed 3 years of follow-up.
During the OL phase, ES and DS patients showed comparable ARRs (0.20-0.22) and
similar numbers of gadolinium-enhancing T1 ( p = 0.49) and new or enlarging T2
lesions ( p = 0.51) at Year 3. ES patients showed significantly smaller changes
in gray matter volume than DS patients from Months 12 to 36 (mean difference,
0.371%; p = 0.015), with similar trend in whole-brain volume ( p = 0.080).
Adverse events were mild, consistent with the well-established glatiramer acetate
(GA) safety profile. CONCLUSION: GA40 conferred treatment benefit over 3 years:
sustained low ARR and lesion activity and favorable safety.
PMID- 27503906
TI - The impact of drugs for multiple sclerosis on sleep.
AB - Although there is a growing literature on the presence of sleep disorders in
multiple sclerosis (MS), few studies have specifically addressed the impact of
drugs on sleep of these patients. Moreover, even when sleep is considered,
quantitative assessment by standardized questionnaires or polysomnography is
lacking. The studies that have been done highlight that interferon-beta and some
symptomatic medications may affect sleep, thus contributing to fatigue,
depression, and poor quality of life; conversely, natalizumab and cannabinoids
may improve sleep. Common limitations of the literature reviewed here are small
sample size, selection bias, and often a lack of objective outcome measures.
Clinicians need to remember to ask about sleep in all MS patients and intervene
when appropriate. A systematic approach that takes sleep into account is
recommended to enhance recognition and appropriate management of sleep
disruption, including disorders related to medication. Consideration of the
impact on sleep should also be part of the design of trials of new therapies.
PMID- 27503907
TI - Increased ex vivo antigen presentation profile of B cells in multiple sclerosis.
AB - BACKGROUND: Multiple sclerosis (MS) is thought to be T cell mediated but the
mechanisms eliciting such a dysregulated adaptative immune response remain
enigmatic. OBJECTIVE: To examine the activation profile of antigen-presenting
cells (APCs) in MS. METHODS: A total of 98 study subjects were enrolled including
patients suffering from relapsing-remitting, secondary- and primary-progressive
(PP) MS, other inflammatory neurological diseases, and healthy controls. Blood
monocytes and B cells were stimulated using specific ligands of toll-like
receptors (TLRs) or inflammasomes or Epstein-Barr virus (EBV) particles. Their
activation profile was determined before or after stimulation by flow cytometry
(CD40, CD80, CD83, CD86, and human leukocyte antigen-antigen D related (HLA-DR))
and Luminex assay, measuring the concentration of eight cytokines in culture
supernatants. Differences among groups were assessed in a linear model framework.
RESULTS: We demonstrate that relapsing MS patients exhibit an increased
expression of HLA-DR and CD40 ex vivo, mostly at the surface of B cells. Specific
stimulations of TLR or inflammasomes enhance the expression of components of the
immunological synapse and the cytokine secretion but without differences between
categories of study subjects. CONCLUSION: These data suggest that the activation
profile of B cells is increased in MS. However, the perception of the danger
signal by B lymphocytes and monocytes does not seem to be different in MS
patients as compared to control subjects.
PMID- 27503908
TI - Can Neurological Biomarkers of Brain Impairment Be Used to Predict Poststroke
Motor Recovery? A Systematic Review.
AB - Background There is growing interest to establish recovery biomarkers, especially
neurological biomarkers, in order to develop new therapies and prediction models
for the promotion of stroke rehabilitation and recovery. However, there is no
consensus among the neurorehabilitation community about which biomarker(s) have
the highest predictive value for motor recovery. Objective To review the evidence
and determine which neurological biomarker(s) meet the high evidence quality
criteria for use in predicting motor recovery. Methods We searched databases for
prognostic neuroimaging/neurophysiological studies. Methodological quality of
each study was assessed using a previously employed comprehensive 15-item rating
system. Furthermore, we used the GRADE approach and ranked the overall evidence
quality for each category of neurologic biomarker. Results Seventy-one articles
met our inclusion criteria; 5 categories of neurologic biomarkers were
identified: diffusion tensor imaging (DTI), transcranial magnetic stimulation
(TMS), functional magnetic resonance imaging (fMRI), conventional structural MRI
(sMRI), and a combination of these biomarkers. Most studies were conducted with
individuals after ischemic stroke in the acute and/or subacute stage (~70%). Less
than one-third of the studies (21/71) were assessed with satisfactory
methodological quality (80% or more of total quality score). Conventional
structural MRI and the combination biomarker categories ranked "high" in overall
evidence quality. Conclusions There were 3 prevalent methodological limitations:
(a) lack of cross-validation, (b) lack of minimal clinically important difference
(MCID) for motor outcomes, and (c) small sample size. More high-quality studies
are needed to establish which neurological biomarkers are the best predictors of
motor recovery after stroke. Finally, the quarter-century old methodological
quality tool used here should be updated by inclusion of more contemporary
methods and statistical approaches.
PMID- 27503910
TI - Hsp90-binding immunophilin FKBP52 modulates telomerase activity by promoting the
cytoplasmic retrotransport of hTERT.
AB - Telomerase is a unique ribonucleoprotein enzyme that is required for continued
cell proliferation. To generate catalytically active telomerase, human telomerase
reverse transcriptase (hTERT) must translocate to the nucleus and assemble with
the RNA component of telomerase. The molecular chaperones heat shock protein 90
(Hsp90) and p23 maintain hTERT in a conformation that enables nuclear
translocation. However, the regulatory role of chaperones in nuclear transport of
hTERT remains unclear. In this work, we demonstrate that immunophilin FK506
binding protein (FKBP)52 linked the hTERT-Hsp90 complex to the dynein-dynactin
motor, thereby promoting the transport of hTERT to the nucleus along
microtubules. FKBP52 interacted with the hTERT-Hsp90 complex through binding of
the tetratricopeptide repeat domain to Hsp90 and binding of the dynamitin (Dyt)
component of the dynein-associated dynactin complex to the peptidyl prolyl
isomerase domain. The depletion of FKBP52 inhibited nuclear transport of hTERT,
resulting in cytoplasmic accumulation. Cytoplasmic hTERT was rapidly degraded
through ubiquitin (Ub)-dependent proteolysis, thereby abrogating telomerase
activity. In addition, overexpression of dynamitin, which is known to dissociate
the dynein-dynactin motor from its cargoes, reduced telomerase activity.
Collectively, these results provide a molecular mechanism by which FKBP52
modulates telomerase activity by promoting dynein-dynactin-dependent nuclear
import of hTERT.
PMID- 27503909
TI - Gsk3beta and Tomm20 are substrates of the SCFFbxo7/PARK15 ubiquitin ligase
associated with Parkinson's disease.
AB - Fbxo7 is a clinically relevant F-box protein, associated with both cancer and
Parkinson's disease (PD). Additionally, SNPs within FBXO7 are correlated with
alterations in red blood cell parameters. Point mutations within FBXO7 map within
specific functional domains, including near its F-box domain and its substrate
recruiting domains, suggesting that deficiencies in SCFFbxo7/PARK15 ubiquitin
ligase activity are mechanistically linked to early-onset PD. To date, relatively
few substrates of the ligase have been identified. These include HURP (hepatoma
up-regulated protein), whose ubiquitination results in proteasome-mediated
degradation, and c-IAP1 (inhibitor of apoptosis protein 1), TNF receptor
associated factor 2 (TRAF2), and NRAGE, which are not destabilized as a result of
ubiquitination. None of these substrates have been linked directly to PD, nor has
it been determined whether they would directly engage neuronal cell death
pathways. To discover ubiquitinated substrates of SCFFbxo7 implicated more
directly in PD aetiology, we conducted a high-throughput screen using protein
arrays to identify new candidates. A total of 338 new targets were identified and
from these we validated glycogen synthase kinase 3beta (Gsk3beta), which can
phosphorylate alpha-synuclein, and translocase of outer mitochondrial membrane 20
(Tomm20), a mitochondrial translocase that, when ubiquitinated, promotes
mitophagy, as SCFFbxo7 substrates both in vitro and in vivo Ubiquitin chain
restriction analyses revealed that Fbxo7 modified Gsk3beta using K63 linkages.
Our results indicate that Fbxo7 negatively regulates Gsk3beta activity, rather
than its levels or localization. In addition, Fbxo7 ubiquitinated Tomm20, and its
levels correlated with Fbxo7 expression, indicating a stabilizing effect. None of
the PD-associated mutations in Fbxo7 impaired Tomm20 ubiquitination. Our findings
demonstrate that SCFFbxo7 has an impact directly on two proteins implicated in
pathological processes leading to PD.
PMID- 27503911
TI - Using the Intervention Mapping Protocol to develop an online video intervention
for parents to prevent childhood obesity: Movie Models.
AB - BACKGROUND: The increasing prevalence of childhood overweight/obesity caused by
an unhealthy diet, insufficient physical activity (PA) and high levels of
sedentary behaviour (SB) is a prominent public health concern. Parenting
practices may contribute to healthy behaviour change in children, but well
researched examples are limited. The aim of this study is to describe the
systematic development of an intervention for parents to prevent childhood
overweight/obesity through the improvement of parenting practices. METHODS: The
six steps of the Intervention Mapping Protocol (IMP), a theory- and evidence
based tool to develop health-related interventions, were used as a framework to
develop the 'Movie Models' programme. RESULTS: In Step 1, a needs assessment was
performed to better understand the health problem of overweight/obesity in
children and its association with diet, PA and SB. In Step 2, the programme goal
(increasing the adoption of effective parenting practices) was sub-divided into
performance objectives. Change objectives, which specify explicit actions
required to accomplish the performance objectives, were also identified. Step 3
included the selection of theoretical methods (e.g. 'modelling' and 'images'),
which were then translated into the practical strategy of online parenting
videos. Step 4 comprised the development of a final intervention framework, and
Step 5 included the planning of programme adoption and implementation. The final
phase, Step 6, included the development of an effect- and process-evaluation
plan. DISCUSSION: The IMP was used to structure the development of 'Movie
Models', an intervention targeting specific parenting practices related to
children's healthy diet, PA, SB, and parental self-efficacy. A clear framework
for process analyses is offered, which aims to increase the potential
effectiveness of an intervention and can be useful for those developing health
promotion programmes.
PMID- 27503912
TI - Somatic Complaints Are Significantly Associated with Chronic Uninvestigated
Dyspepsia and Its Symptoms: A Large Cross-sectional Population Based Study.
AB - Background/Aims: Somatization may influence persistence and severity of symptoms
in gastrointestinal diseases. Some studies suggest that somatization is
associated with chronic uninvestigated dyspepsia (CUD); however, the association
is unclear. We aimed to determine the association between the profiles of somatic
complaints with CUD and its symptoms. Methods: In a cross-sectional study
conducted on 4763 Iranian adults, somatic complaints were assessed using a
comprehensive 31-items questionnaire. Patients with CUD were identified by the
Rome III diagnostic criteria. Profiles of somatic complaints were derived from
factor analysis. Logistic regression analysis was used to assess the relationship
between extracted profiles with CUD and its symptoms. Results: CUD, bothersome
postprandial fullness, early satiation, and epigastric pain or burning was
identified in 723 (15.2%), 384 (8.1%), 302 (6.3%), and 371 (7.8%) of the study
population. The frequency of all 31 somatic complaints was significantly higher
in patients with CUD compared with controls (P < 0.001), and the most frequent
was severe fatigue (45.1%). The profiles of somatic complaints were extracted in
4 domains, including "psychological", "gastrointestinal", "neuro-skeletal", and
"pharyngeal-respiratory". The psychological (OR, 1.49; 95% CI, 1.44-1.54),
gastrointestinal (OR, 2.22; 95% CI, 2.09-2.37), neuro-skeletal (OR, 1.52; 95% CI,
1.44-1.59), and pharyngeal-respiratory (OR, 2.09; 95% CI, 1.94-2.25) profiles
were significantly associated with greater odds of CUD. Conclusions: CUD and its
symptoms are strongly associated with higher levels of somatic complaints and
their related extracted profiles. This perhaps explains that why it can be
difficult to treat, however further prospective investigations are required to
confirm these associations.
PMID- 27503913
TI - Vertebral column anomalies in Indo-Pacific and Atlantic humpback dolphins Sousa
spp.
AB - Conspicuous vertebral column abnormalities in humpback dolphins (genus Sousa)
were documented for the first time during 3 photo-identification field studies of
small populations in Taiwan, Senegal and Angola. Seven Taiwanese humpback
dolphins S. chinensis taiwanensis with vertebral column anomalies (lordosis,
kyphosis or scoliosis) were identified, along with 2 possible cases of vertebral
osteomyelitis. There was evidence from several individuals photographed over
consecutive years that the anomalies became more pronounced with age. Three
Atlantic humpback dolphins S. teuszii were observed with axial deviations of the
vertebral column (lordosis and kyphosis). Another possible case was identified in
a calf, and 2 further animals were photographed with dorsal indents potentially
indicative of anomalies. Vertebral column anomalies of humpback dolphins were
predominantly evident in the lumbo-caudal region, but one Atlantic humpback
dolphin had an anomaly in the cervico-thoracic region. Lordosis and kyphosis
occurred simultaneously in several individuals. Apart from the described
anomalies, all dolphins appeared in good health and were not obviously
underweight or noticeably compromised in swim speed. This study presents the
first descriptions of vertebral column anomalies in the genus Sousa. The
causative factors for the anomalies were unknown in every case and are
potentially diverse. Whether these anomalies result in reduced fitness of
individuals or populations merits attention, as both the Taiwanese and Atlantic
humpback dolphin are species of high conservation concern.
PMID- 27503914
TI - Acute necrotizing colitis with pneumatosis intestinalis in an Amazonian manatee
calf.
AB - On 25 January 2014, a 1 mo old female Amazonian manatee Trichechus inunguis calf
weighing 12 kg was rescued by air transport in Guajara, Brazil, and transferred
to Mamiraua Institute's Community-based Amazonian Manatee Rehabilitation Center.
The calf presented piercing/cutting lesions on the back, neck, and head, in
addition to dehydration and intermittent involuntary buoyancy. X-ray analysis
revealed a large amount of gases in the gastrointestinal tract. Daily procedures
included wound cleaning and dressing, clinical and laboratory monitoring,
treatment for intestinal tympanism, and artificial feeding. Adaptation to the
nursing formula included 2 kinds of whole milk. Up to 20 d post-rescue the calf
presented appetite, was active, and gained weight progressively. Past this period
the calf started losing weight and presented constant involuntary buoyancy and
died after 41 d in rehabilitation. The major findings at necropsy were
pneumatosis intestinalis in cecum and colon, pulmonary edema, and hepatomegaly.
The microscopic examination revealed pyogranulomatous and necrohemohrragic
colitis with multinucleated giant cells, acute multifocal lymphadenitis with
lymphoid depletion in cortical and paramedullary regions of mesenteric lymph
nodes, and diffuse severe acinar atrophy of the pancreas. Anaerobic cultures of
fragments of cecum and colon revealed colonies genotyped as Clostridium
perfringens type A. We speculate that compromised immunity, thermoregulatory
failure, and intolerance to artificial diet may have been contributing factors to
the infection, leading to enterotoxemia and death.
PMID- 27503915
TI - Molecular and pathological characterization of Fusarium solani species complex
infection in the head and lateral line system of Sphyrna lewini.
AB - A severe fungal infection affecting the head and lateral line system was
diagnosed in 7 captive scalloped hammerhead sharks Sphyrna lewini in an aquarium
in Thailand. Extensive and severe necrotizing cellulitis was consistently
observed microscopically along the cephalic and lateral line canals in
conjunction with positive fungal cultures for Fusarium sp. Molecular phylogenetic
analysis was performed from 3 isolates based on the nucleotide sequences
containing internally transcribed spacer (ITS) and a portion of 5.8S and 28S
rDNA. The fungus was highly homologous (100%) and closely related to F. solani
species complex 2 (FSSC 2), which belongs to Clade 3 of the FSSC. Our results
illustrate the histopathological findings and expand upon our knowledge of the
prevalence of invasive fusariosis in the head and lateral line system of
hammerhead sharks.
PMID- 27503916
TI - First identification of Francisella noatunensis subsp. orientalis causing
mortality in Mexican tilapia Oreochromis spp.
AB - Francisellosis, an emerging disease in tilapia Oreochromis spp., is caused by the
facultative, intracellular bacterium Francisella noatunensis subsp. orientalis,
which is present in various countries where tilapia farming is commercially
important. We confirmed the presence of francisellosis in Mexican tilapia
cultures in association with an outbreak during the second semester of 2012.
Broodstock fish presented a mortality rate of approximately 40%, and disease was
characterized by histologically classified granulomas, or whitish nodules, in
different organs, mainly the spleen and kidney. Through DNA obtained from
infected tissue and pure cultures in a cysteine heart medium supplemented with
hemoglobin, F. noatunensis subsp. orientalis was initially confirmed through the
amplification and analysis of the 16S rRNA gene and the internal transcribed
spacer region. Phylogenetic analysis of these genes demonstrated close similarity
with previously reported F. noatunensis subsp. orientalis sequences obtained from
infected tilapia from various countries. The identification of this subspecies as
the causative agent of the outbreak was confirmed using the iglC gene as a target
sequence, which showed 99.5% identity to 2 F. noatunensis subsp. orientalis
strains (Ethime-1 and Toba04). These findings represent the first documented
occurrence of francisellosis in Mexican tilapia cultures, which highlights the
importance of establishing preventative measures to minimize the spread of this
disease within the Mexican aquaculture industry.
PMID- 27503917
TI - Virulence of Flavobacterium columnare genomovars in rainbow trout Oncorhynchus
mykiss.
AB - Flavobacterium columnare is the causative agent of columnaris disease and is
responsible for significant economic losses in aquaculture. F. columnare is a
Gram-negative bacterium, and 5 genetic types or genomovars have been described
based on restriction fragment length polymorphism of the 16S rRNA gene. Previous
research has suggested that genomovar II isolates are more virulent than
genomovar I isolates to multiple species of fish, including rainbow trout
Oncorhynchus mykiss. In addition, improved genotyping methods have shown that
some isolates previously classified as genomovar I, and used in challenge
experiments, were in fact genomovar III. Our objective was to confirm previous
results with respect to genomovar II virulence, and to determine the
susceptibility of rainbow trout to other genomovars. The virulence of 8 genomovar
I, 4 genomovar II, 3 genomovar II-B, and 5 genomovar III isolates originating
from various sources was determined through 3 independent challenges in rainbow
trout using an immersion challenge model. Mean cumulative percent mortality (CPM)
of ~49% for genomovar I isolates, ~1% for genomovar II, ~5% for the II-B
isolates, and ~7% for the III isolates was observed. The inability of genomovar
II isolates to produce mortalities in rainbow trout was unanticipated based on
previous studies, but may be due to a number of factors including rainbow trout
source and water chemistry. The source of fish and/or the presence of sub-optimal
environment may influence the susceptibility of rainbow trout to different F.
columnare genomovars.
PMID- 27503918
TI - High prevalence of Enterocytozoon hepatopenaei in shrimps Penaeus monodon and
Litopenaeus vannamei sampled from slow growth ponds in India.
AB - Hepatopancreatic microsporidiosis in cultivated Litopenaeus vannamei and Penaeus
monodon is caused by the newly emerged pathogen Enterocytozoon hepatopenaei
(EHP). It has been detected in shrimp cultured in China, Vietnam and Thailand and
is suspected to have occurred in Malaysia and Indonesia and to be associated with
severely retarded growth. Due to retarded shrimp growth being reported at farms
in the major grow-out states of Tamilnadu, Andhra Pradesh and Odisha in India,
shrimp were sampled from a total of 235 affected ponds between March 2014 and
April 2015 to identify the presence of EHP. PCR and histology detected a high
prevalence of EHP in both P. monodon and L. vannamei, and infection was confirmed
by in situ hybridization using an EHP-specific DNA probe. Histology revealed
basophilic inclusions in hepatopancreas tubule epithelial cells in which EHP was
observed at various developmental stages ranging from plasmodia to mature spores.
The sequence of a region of the small subunit rDNA gene amplified by PCR was
found to be identical to EHP sequences deposited in GenBank. Bioassays confirmed
that EHP infection could be transmitted orally to healthy shrimp. Histology also
identified bacterial co-infections in EHP-infected shrimp sampled from slow
growth ponds with low-level mortality. The data confirm that hepatopancreatic
microsporidiosis caused by EHP is prevalent in shrimp being cultivated in India.
EHP infection control measures thus need to be implemented urgently to limit
impacts of slowed shrimp growth.
PMID- 27503919
TI - Ostreid herpesvirus in wild oysters from the Huelva coast (SW Spain).
AB - This is the first report of ostreid herpesvirus 1 microvariant (OsHV-1 uVar)
infecting natural oyster beds located in Huelva (SW Spain). The virus was
detected in 3 oyster species present in the intertidal zone: Crassostrea gigas
(Thunberg, 1793), C. angulata (Lamarck, 1819) and, for the first time, in Ostrea
stentina Payraudeau, 1826. Oysters were identified by a specific polymerase chain
reaction (PCR) and posterior restriction fragment length polymorphism (RFLP)
analysis based on cytochrome oxidase I (COI) mitochondrial DNA. Results confirmed
that C. angulata still remains the dominant oyster population in SW Spain despite
the introduction of C. gigas for cultivation in the late 1970s, and its
subsequent naturalization. C. angulata shows a higher haplotype diversity than C.
gigas. OsHV-1 virus was detected by PCR with C2/C6 pair primers. Posterior RFLP
analyses with the restriction enzyme MfeI were done in order to reveal the OsHV-1
uVar. Detections were confirmed by DNA sequencing, and infections were evidenced
by in situ hybridization in C. gigas, C. angulata and O. stentina samples. The
prevalence was similar among the 3 oyster species but varied between sampling
locations, being higher in areas with greater harvesting activities. OsHV-1 uVar
accounted for 93% of all OsHV-1 detected.
PMID- 27503920
TI - Detection of Brucella spp. in bottlenose dolphins Tursiops truncatus by a real
time PCR using blowhole swabs.
AB - Blowhole swabs are a simple and non-invasive method for collecting samples from
cetaceans and can be used for screening large numbers of animals in the field.
This study reports a real-time PCR assay for the detection of Brucella spp. using
blowhole swab samples from bottlenose dolphins Tursiops truncatus stranded in the
coastal region of Virginia, South Carolina and northern Florida, USA, between
2013 and 2015. We used real-time PCR results on lung samples from the same
dolphins in order to estimate the relative sensitivity and specificity of real
time PCR of blowhole swabs. Brucella DNA was detected in lung tissue of 22%
(18/81) and in blowhole swabs of 21% (17/81) of the sampled dolphins. The
relative sensitivity and specificity of real-time PCR on blowhole swabs as
compared to the real-time PCR on lung samples was 94% (17/18) and 100% (63/63),
respectively. These results indicate that real-time PCR on blowhole swabs may be
used as a non-invasive test for rapid detection of Brucella spp. in the
respiratory tract of dolphins. To our knowledge, this is the first report on the
use of blowhole swabs for detection of bacterial pathogens by real-time PCR in
bottlenose dolphins.
PMID- 27503921
TI - Cutaneous malignant melanoma in a Haller's round ray Urobatis halleri.
AB - Multiple black raised nodular masses were noted on the dorsal surface of an adult
male Haller's round ray Urobatis halleri. Biopsy of 2 masses was performed, and
histopathology revealed proliferative sheets of melanocytes exhibiting mild
anisocytosis and anisokaryosis, supporting a diagnosis of malignant melanoma.
Approximately 2 mo following the biopsy procedure, the round ray became acutely
anorexic and was found dead in its enclosure. A full necropsy was performed, and
tissues were submitted for histopathology. The black raised nodular masses again
exhibited histologic features of a melanoma. In addition to the nodular masses
present, multiple flat areas of increased pigmentation were also present
throughout the course of the case and were not suggestive of neoplasia
histologically. The transformation of benign to malignant neoplasia has been well
described in other species and may have played a role in the development of
multiple tumors in this case.
PMID- 27503922
TI - Larvae of Contracaecum sp. (Nematoda: Anisakidae) in the threatened freshwater
fish Sandelia capensis (Anabantidae) in South Africa.
AB - Third-stage larvae of the nematode genus Contracaecum Railliet et Henry, 1912
(Contracaecum sp.) were, for the first time, recorded from the abdominal cavity
of the threatened endemic freshwater fish Sandelia capensis (Cuvier) in South
Africa. The larval morphology indicated that they belong to a species of which
the adults are parasitic in fish-eating birds. Although the nematode seems to be
a common parasite of S. capensis in the locality under study (prevalence 23%),
the low intensity of infection recorded (1 to 4) and the generally known low
pathogenicity of Contracaecum larvae in fish indicate that this parasite probably
does not represent a danger to the local population of this threatened fish
species.
PMID- 27503923
TI - Draining and liming of ponds as an effective measure for containment of CyHV-3 in
carp farms.
AB - Infections of common carp Cyprinus carpio and koi, its coloured morphotypes, with
the cyprinid herpesvirus 3 (CyHV-3) can induce severe clinical signs and
increased mortality in affected stocks. This may significantly challenge the
economic basis of carp farming in Central Europe. To limit virus spread in carp
farms, effective disinfection measures for ponds stocked with infected
populations are required. In the traditional European pond aquaculture of carp,
draining and liming of ponds with quicklime (CaO) up to pH 12 is a well
established disinfection measure against various pathogens. The present field
study investigated whether these measures are sufficient for the inactivation of
CyHV-3 infectivity in carp ponds. After draining and liming, the ponds were
stocked with carp fry from a CyHV-3-negative stock, and 2 ponds were examined for
the presence of CyHV-3-specific DNA sequences during the growth period of the
carp and in the harvested stock. Wild fish (from the ponds, and feeder and
drainage canals) and water samples (from the ponds) were also examined for CyHV-3
specific DNA sequences; and naive carp were cohabited with wild fish, or exposed
to the pondwater samples, to test for the presence of infectious virus. All
examined samples remained negative for CyHV-3 throughout the study. This
indicates that draining and liming with quicklime can be a suitable disinfection
measure for ponds after a CyHV-3 outbreak in carp aquaculture.
PMID- 27503924
TI - RNA Sequencing Identifies Transcriptionally Viable Gene Fusions in Esophageal
Adenocarcinomas.
AB - Esophageal adenocarcinoma is a deadly cancer with increasing incidence in the
United States, but mechanisms underlying pathogenesis are still mostly elusive.
In addressing this question, we assessed gene fusion landscapes by comprehensive
RNA sequencing (RNAseq) of 55 pretreatment esophageal adenocarcinoma and 49
nonmalignant biopsy tissues from patients undergoing endoscopy for Barrett's
esophagus. In this cohort, we identified 21 novel candidate esophageal
adenocarcinoma-associated fusions occurring in 3.33% to 11.67% of esophageal
adenocarcinomas. Two candidate fusions were selected for validation by PCR and
Sanger sequencing in an independent set of pretreatment esophageal adenocarcinoma
(N = 115) and nonmalignant (N = 183) biopsy tissues. In particular, we observed
RPS6KB1-VMP1 gene fusion as a recurrent event occurring in approximately 10% of
esophageal adenocarcinoma cases. Notably, esophageal adenocarcinoma cases
harboring RPS6KB1-VMP1 fusions exhibited significantly poorer overall survival as
compared with fusion-negative cases. Mechanistic investigations established that
the RPS6KB1-VMP1 transcript coded for a fusion protein, which significantly
enhanced the growth rate of nondysplastic Barrett's esophagus cells. Compared
with the wild-type VMP1 protein, which mediates normal cellular autophagy,
RPS6KB1-VMP1 fusion exhibited aberrant subcellular localization and was
relatively ineffective in triggering autophagy. Overall, our findings identified
RPS6KB1-VMP1 as a genetic fusion that promotes esophageal adenocarcinoma by
modulating autophagy-related processes, offering new insights into the molecular
pathogenesis of esophageal adenocarcinomas. Cancer Res; 76(19); 5628-33. (c)2016
AACR.
PMID- 27503925
TI - Assessing Immune-Related Adverse Events of Efficacious Combination
Immunotherapies in Preclinical Models of Cancer.
AB - New combination immunotherapies are displaying both efficacy and immune-related
adverse events (irAE) in humans. However, grade 3/4 irAEs occur in a high
proportion, which can lead to discontinuation of treatment and can result in
fatalities if not promptly treated. Prolonged T regulatory cell (Treg) depletion
in tumor-bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum
of antitumor responses and severity of irAEs that can occur in
ipilimumab/nivolumab-treated patients. In contrast, transient Treg depletion or
anti-CTLA-4/PD-1 therapy had equivalent effects in mice, lowering the immune
tolerance threshold and allowing irAEs to be more easily induced following
treatment with additional immunomodulatory antibodies. Transient Treg depletion
of DT in combination with anti-PD-1 or anti-TIM-3 monoclonal antibodies had a
high therapeutic window compared with DT plus anti-CD137. In contrast, DT plus
anti-CD137-treated mice developed severe irAEs similar to grade 3/4 clinical
symptoms. These irAEs appeared because of an infiltration of activated
proliferating effector T cells in the tissues producing IFNgamma and TNF;
however, TNF blockade decreased irAEs severity without impacting on tumor growth.
Cancer Res; 76(18); 5288-301. (c)2016 AACR.
PMID- 27503926
TI - SIRT2 Deacetylates and Inhibits the Peroxidase Activity of Peroxiredoxin-1 to
Sensitize Breast Cancer Cells to Oxidant Stress-Inducing Agents.
AB - SIRT2 is a protein deacetylase with tumor suppressor activity in breast and liver
tumors where it is mutated; however, the critical substrates mediating its
antitumor activity are not fully defined. Here we demonstrate that SIRT2 binds,
deacetylates, and inhibits the peroxidase activity of the antioxidant protein
peroxiredoxin (Prdx-1) in breast cancer cells. Ectopic overexpression of SIRT2,
but not its catalytically dead mutant, increased intracellular levels of reactive
oxygen species (ROS) induced by hydrogen peroxide, which led to increased levels
of an overoxidized and multimeric form of Prdx-1 with activity as a molecular
chaperone. Elevated levels of SIRT2 sensitized breast cancer cells to
intracellular DNA damage and cell death induced by oxidative stress, as
associated with increased levels of nuclear FOXO3A and the proapoptotic BIM
protein. In addition, elevated levels of SIRT2 sensitized breast cancer cells to
arsenic trioxide, an approved therapeutic agent, along with other intracellular
ROS-inducing agents. Conversely, antisense RNA-mediated attenuation of SIRT2
reversed ROS-induced toxicity as demonstrated in a zebrafish embryo model system.
Collectively, our findings suggest that the tumor suppressor activity of SIRT2
requires its ability to restrict the antioxidant activity of Prdx-1, thereby
sensitizing breast cancer cells to ROS-induced DNA damage and cell cytotoxicity.
Cancer Res; 76(18); 5467-78. (c)2016 AACR.
PMID- 27503927
TI - Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells.
AB - The stress-induced chaperone protein Hsp70 enables the initiation and progression
of many cancers, making it an appealing therapeutic target for development. Here,
we show that cancer cells resistant to Hsp70 inhibitors in vitro remain sensitive
to them in vivo, revealing the pathogenic significance of Hsp70 in tumor stromal
cells rather than tumor cells as widely presumed. Using transgenic mouse models
of cancer, we found that expression of Hsp70 in host stromal cells was essential
to support tumor growth. Furthermore, genetic ablation or pharmacologic
inhibition of Hsp70 suppressed tumor infiltration by macrophages needed to enable
tumor growth. Overall, our results illustrate how Hsp70 inhibitors mediate the
anticancer effects by targeting both tumor cells and tumor stromal cells, with
implications for the broad use of these inhibitors as tools to ablate tumor
associated macrophages that enable malignant progression. Cancer Res; 76(20);
5926-32. (c)2016 AACR.
PMID- 27503928
TI - Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial
Tumor Cell Invasion and Metastasis.
AB - Snail1 transcriptional factor is essential for triggering epithelial-to
mesenchymal transition (EMT) and inducing tumor cell invasion. We report here an
EMT-independent action of Snail1 on tumor invasion, as it is required for the
activation of cancer-associated fibroblasts (CAF). Snail1 expression in
fibroblasts requires signals derived from tumor cells, such as TGFbeta;
reciprocally, in fibroblasts, Snail1 organizes a complex program that stimulates
invasion of epithelial cells independent of the expression of Snail1 in these
cells. Epithelial cell invasion is stimulated by the secretion by fibroblast of
diffusible signaling molecules, such as prostaglandin E2 The capability of human
or murine CAFs to promote tumor invasion is dependent on Snail1 expression.
Inducible Snail1 depletion in mice decreases the invasion of breast tumors;
moreover, epithelial tumor cells coxenografted with Snail1-depleted fibroblasts
originated tumors with lower invasion than those transplanted with control
fibroblasts. Therefore, these results demonstrate that the role of Snail1 in
tumor invasion is not limited to EMT, but it is also dependent on its activity in
stromal fibroblasts, where it orchestrates the cross-talk with epithelial tumor
cells. Cancer Res; 76(21); 6205-17. (c)2016 AACR.
PMID- 27503929
TI - Chromatin-Remodeling Complex SWI/SNF Controls Multidrug Resistance by
Transcriptionally Regulating the Drug Efflux Pump ABCB1.
AB - Anthracyclines are among the most effective yet most toxic drugs used in the
oncology clinic. The nucleosome-remodeling SWI/SNF complex, a potent tumor
suppressor, is thought to promote sensitivity to anthracyclines by recruiting
topoisomerase IIa (TOP2A) to DNA and increasing double-strand breaks. In this
study, we discovered a novel mechanism through which SWI/SNF influences
resistance to the widely used anthracycline doxorubicin based on the use of a
forward genetic screen in haploid human cells, followed by a rigorous single and
double-mutant epistasis analysis using CRISPR/Cas9-mediated engineering.
Doxorubicin resistance conferred by loss of the SMARCB1 subunit of the SWI/SNF
complex was caused by transcriptional upregulation of a single gene, encoding the
multidrug resistance pump ABCB1. Remarkably, both ABCB1 upregulation and
doxorubicin resistance caused by SMARCB1 loss were dependent on the function of
SMARCA4, a catalytic subunit of the SWI/SNF complex. We propose that residual
SWI/SNF complexes lacking SMARCB1 are vital determinants of drug sensitivity, not
just to TOP2A-targeted agents, but to the much broader range of cancer drugs
effluxed by ABCB1. Cancer Res; 76(19); 5810-21. (c)2016 AACR.
PMID- 27503930
TI - TPL2 Is an Oncogenic Driver in Keratocanthoma and Squamous Cell Carcinoma.
AB - Squamous cell carcinoma (SCC) and keratoacanthoma (KA; SCC/KA) research has been
hampered mainly by our lack of understanding the underlying genetic and
epigenetic alterations associated with SCC/KA development, as well as the lack of
animal models that faithfully recapitulate histopathologic features of human
SCC/KA. Here, we show that TPL2 overexpression induced both cell transformation
in immortalized human keratinocytes and SCC and KA-like cutaneous SCC (cSCC)
development in mice. Mechanistically, activation of TPL2 downstream signaling
pathways such as MEK/ERK MAPK, mTOR, NF-kappaB, and p38 MAPK leads to TPL2
mediated cell transformation in immortalized human keratinocytes and
tumorigenesis in mice. Most importantly, TPL2 overexpression is required for
iTPL2 TG-driven SCC and KA-like cSCC tumor maintenance, validating TPL2 as a
possible drug target for the treatment of SCC/KA. Finally, we verified that TPL2
is overexpressed in human cutaneous metastatic SCC and KA clinical specimens
compared with normal skin. Taken together, our results establish TPL2 as an
oncogenic driver in SCC/KA development. Cancer Res; 76(22); 6712-22. (c)2016
AACR.
PMID- 27503931
TI - Inhibiting Mitochondrial DNA Ligase IIIalpha Activates Caspase 1-Dependent
Apoptosis in Cancer Cells.
AB - Elevated levels of DNA ligase IIIalpha (LigIIIalpha) have been identified as a
biomarker of an alteration in DNA repair in cancer cells that confers
hypersensitivity to a LigIIIalpha inhibitor, L67, in combination with a poly (ADP
ribose) polymerase inhibitor. Because LigIIIalpha functions in the nucleus and
mitochondria, we examined the effect of L67 on these organelles. Here, we show
that, although the DNA ligase inhibitor selectively targets mitochondria, cancer
and nonmalignant cells respond differently to disruption of mitochondrial DNA
metabolism. Inhibition of mitochondrial LigIIIalpha in cancer cells resulted in
abnormal mitochondrial morphology, reduced levels of mitochondrial DNA, and
increased levels of mitochondrially generated reactive oxygen species that caused
nuclear DNA damage. In contrast, these effects did not occur in nonmalignant
cells. Furthermore, inhibition of mitochondrial LigIIIalpha activated a caspase 1
dependent apoptotic pathway, which is known to be part of inflammatory responses
induced by pathogenic microorganisms in cancer, but not nonmalignant cells. These
results demonstrate that the disruption of mitochondrial DNA metabolism elicits
different responses in nonmalignant and cancer cells and suggests that the
abnormal response in cancer cells may be exploited in the development of novel
therapeutic strategies that selectively target cancer cells. Cancer Res; 76(18);
5431-41. (c)2016 AACR.
PMID- 27503932
TI - Adaptive NK Cells with Low TIGIT Expression Are Inherently Resistant to Myeloid
Derived Suppressor Cells.
AB - Human cytomegalovirus (CMV)-induced adaptive natural killer (NK) cells display
distinct phenotypic and functional characteristics, including properties of
immune memory. We hypothesized that these cells may be more resistant to
suppression mediated by immunoregulatory cell subsets, making them attractive for
use in cancer therapy. Here we report that relative to conventional NK cells,
adaptive NK cells express lower levels of the inhibitory receptor T-cell Ig and
ITIM domain (TIGIT), which results in resistance to immune suppression mediated
by myeloid-derived suppressor cells (MDSC), as derived from cytokine induction in
normal blood or patients with myelodysplastic syndrome. In contrast, conventional
NK cells were potently suppressed by MDSCs, an effect abrogated completely by
TIGIT blockade. Mechanistically, TIGIT signaling in NK cells after MDSC coculture
led to a decrease in the phosphorylation of ZAP70/Syk and ERK1/2. These effects
were reversed by blocking TIGIT on NK cells or by inhibiting production of
reactive oxygen species (ROS) by MDSCs, the latter of which upregulated the TIGIT
ligand CD155 on MDSCs. Accordingly, the blunted cytotoxicity of NK cells
cocultured with MDSCs against tumor cells could be reversed by blocking TIGIT or
ROS production. Overall, our results show how adaptive NK cells arising in
response to CMV infection can escape MDSC-mediated suppression, and defined TIGIT
antagonists as a novel type of checkpoint inhibitor to enhance NK-cell-mediated
responses against cancer and infection. Cancer Res; 76(19); 5696-706. (c)2016
AACR.
PMID- 27503933
TI - Tissue Stiffness and Hypoxia Modulate the Integrin-Linked Kinase ILK to Control
Breast Cancer Stem-like Cells.
AB - Breast tumors are stiffer and more hypoxic than nonmalignant breast tissue. Here
we report that stiff and hypoxic microenvironments promote the development of
breast cancer stem-like cells (CSC) through modulation of the integrin-linked
kinase ILK. Depleting ILK blocked stiffness and hypoxia-dependent acquisition of
CSC marker expression and behavior, whereas ectopic expression of ILK stimulated
CSC development under softer or normoxic conditions. Stiff microenvironments also
promoted tumor formation and metastasis in ovo, where depleting ILK significantly
abrogated the tumorigenic and metastatic potential of invasive breast cancer
cells. We further found that the ILK-mediated phenotypes induced by stiff and
hypoxic microenvironments are regulated by PI3K/Akt. Analysis of human breast
cancer specimens revealed an association between substratum stiffness, ILK, and
CSC markers, insofar as ILK and CD44 were expressed in cancer cells located in
tumor regions predicted to be stiff. Our results define ILK as a key
mechanotransducer in modulating breast CSC development in response to tissue
mechanics and oxygen tension. Cancer Res; 76(18); 5277-87. (c)2016 AACR.
PMID- 27503934
TI - Magnetic Resonance-Guided Nasogastric Feeding Tube Placement for Neonates: A
Preclinical Study.
AB - BACKGROUND: Establishing postnatal nutrition delivery is challenging in neonates
with immature sucking and swallowing ability. Enteral feeding is the gold
standard for such patients, but their small size and fragility present challenges
in nasogastric (NG) feeding tube placement. Feeding tubes are typically placed
with x-ray guidance, which provides minimal soft tissue contrast and exposes the
baby to ionizing radiation. This research investigates magnetic resonance (MR)
guidance of NG feeding tube placement in neonates to provide improved soft tissue
visualization without ionizing radiation. MATERIALS AND METHODS: A novel feeding
tube incorporating 3 solenoid coils for real-time tracking and guidance in the MR
environment was developed. The feeding tube was placed 5 times in a rabbit with
conventional x-ray guidance to assess mechanical stability and function. After x
ray procedures, the rabbit was transferred to a neonatal MR system, and the tube
was placed 5 more times. RESULTS: In procedures guided by x-ray and MR, the
feeding tube provided sufficient mechanical strength and functionality to access
the esophagus and stomach of the rabbit. MR imaging provided significantly
improved soft tissue contrast versus x-ray, which aided in proper tube guidance.
Moreover, MR guidance allowed for real-time placement of the tube without the use
of ionizing radiation. CONCLUSIONS: The feasibility and benefits offered by an MR
guided approach to NG feeding tube placement were demonstrated. The ability to
acquire high-quality MR images of soft tissue without ionizing radiation and a
contrast agent, coupled with accurate 3-dimensional device tracking, promises to
have a powerful impact on future neonatal feeding tube placements.
PMID- 27503936
TI - Immunonutrition Is Associated With a Decreased Incidence of Graft-Versus-Host
Disease in Bone Marrow Transplant Recipients: A Meta-Analysis.
AB - INTRODUCTION: Graft-versus-host disease (GVHD) is a serious complication of bone
marrow transplantation (BMT), requiring higher doses of glucocorticoids or
immunosuppressive therapies and further straining transplant recipients.
Immunonutrition, such as vitamins and amino acid supplements, increase immunity
and decrease inflammation and oxidative stress. This meta-analysis examines the
impact of immunonutrition on the incidence of GVHD and postoperative infections
among BMT recipients. METHODS: A comprehensive literature search for all
published randomized controlled trials was conducted with PubMed, Cochrane
Central Registry of Controlled Trials, and Google Scholar (1966-2016). Keywords
in the search included variations of terms related to immunonutrition, such as
"vitamin," "glutamine," and "transplant." Outcomes included incidence of GVHD and
infection. RESULTS: Ten randomized controlled trials involving 681 BMT recipients
were analyzed: 332 receiving immunonutrition and 349 receiving standard
nutrition. Immunonutrition is correlated with a decreased incidence of GVHD by
19% (relative risk [RR] = 0.810, 95% CI: 0.695-0.945, P = .007). There was no
significant difference in the incidence of infections with immunonutrition (RR =
1.016, 95% CI: 0.819-1.261, P = .885). Subgroup analysis of glutamine compared
with N-acetylcysteine, selenium, and eicosapentaenoic acid showed no significant
difference in the incidence of GVHD or infections (RR = 0.913, 95% CI: 0.732
1.139, P = .419; RR = 0.951, 95% CI: 0.732-1.235; P = .708, respectively).
CONCLUSION: The use of immunonutrition is associated with a reduced risk of GVHD
in BMT recipients, potentially as a result of improved immune support and free
radical scavenging. Providing immunonutrient supplements is a valuable adjunct in
the routine care of BMT recipients, helping to alleviate a common and deadly
complication.
PMID- 27503935
TI - Preserved Gut Microbial Diversity Accompanies Upregulation of TGR5 and
Hepatobiliary Transporters in Bile Acid-Treated Animals Receiving Parenteral
Nutrition.
AB - BACKGROUND: Parenteral nutrition (PN) is a lifesaving therapy but is associated
with gut atrophy and cholestasis. While bile acids (BAs) can modulate intestinal
growth via gut receptors, the gut microbiome likely influences gut proliferation
and inflammation. BAs also regulate the bile salt export pump (BSEP) involved in
cholestasis. We hypothesized that the BA receptor agonist oleanolic acid (OA)
regulates gut TGR5 receptor and modulates gut microbiota to prevent PN-associated
injury. MATERIALS AND METHODS: Neonatal piglets were randomized to approximately
2 weeks of isocaloric enteral nutrition (EN), PN, or PN + enteral OA. Serum
alanine aminotransferase, bilirubin, BAs, hepatic BSEP, gut TGR5, gut, liver
morphology, and fecal microbiome utilizing 16S rRNA sequencing were evaluated.
Kruskal-Wallis test, pairwise Mann-Whitney U test, and multilevel logistic
regression analysis were performed. RESULTS: PN support resulted in gut atrophy
substantially prevented by OA. The median (interquartile range) for villous/crypt
ratio was as follows: EN, 3.37 (2.82-3.80); PN, 1.73 (1.54-2.27); and OA, 2.89
(2.17-3.34; P = .006). Pairwise comparisons yielded P = .002 (EN vs PN), P = .180
(EN vs OA), P = .026 (PN vs OA). OA upregulated TGR5 and BSEP without significant
improvement in serum bilirubin ( P = .095). A decreased microbial diversity and
shift toward proinflammatory phylum Bacteroidetes were seen with PN, which was
prevented by OA. CONCLUSIONS: OA prevented PN-associated gut mucosal injury,
Bacterioides expansion, and the decreased microbial diversity noted with PN. This
study demonstrates a novel relationship among PN-associated gut dysfunction, BA
treatment, and gut microbial changes.
PMID- 27503937
TI - Glucagon-Like Peptide 2 Stimulates Postresection Intestinal Adaptation in Preterm
Pigs by Affecting Proteins Related to Protein, Carbohydrate, and Sulphur
Metabolism.
AB - BACKGROUND: Exogenous glucagon-like peptide 2 (GLP-2) stimulates intestinal
adaptation after resection in animal models of pediatric short bowel syndrome
(SBS). It is unknown whether the molecular mechanisms of such GLP-2 effects are
similar to those of postresection spontaneous adaptation. Using preterm pigs as a
model, we hypothesized that GLP-2 treatment would change the intestinal proteome
within the first week after resection, relative to individuals not resected or
resected without GLP-2 treatment. MATERIALS AND METHODS: Two-day-old preterm pigs
were subjected to resection of 50% distal small intestine and fed total
parenteral nutrition without (SBS) or with GLP-2 infusion (3.5 ug/kg/h, SBS+GLP
2) for 5 days. The proteome of the remnant proximal intestine was compared among
the SBS, SBS+GLP-2, and unresected pigs, through gel-based proteomics. RESULTS:
Thirty-two proteins with differential expression were identified. Ten of these
proteins were affected by the resection alone (ie, SBS vs unresected pigs). Five
of these resection-responsive proteins and another 22 proteins were affected by
GLP-2 infusion (ie, SBS+GLP-2 vs SBS or unresected pigs). Resection alone mainly
affected cellular structural proteins, while the added GLP-2 treatment affected
proteins involved in protein processing and the metabolism of protein,
carbohydrate, and sulphur. CONCLUSION: In the first days following resection,
proteins affected by resection plus GLP-2 treatment differed markedly from those
affected by the spontaneous intestinal adaptation following resection alone.
Whether more long-term GLP-2 treatment may affect the intestinal proteome
following intestinal resection remains unknown.
PMID- 27503938
TI - Decision Aid for Nutrition Support in Pediatric Oncology: A Pilot Study.
AB - BACKGROUND: Despite the importance of nutrition support in preventing
malnutrition in pediatric oncology, the decision to initiate and choose which
nutrition support method is most appropriate can be difficult for parents and
healthcare professionals. Decision aids are decision-focused patient information
materials. They can improve knowledge, reduce decisional conflict, improve
patients' risk perception, and increase patient participation in the decision
making process. They have never been evaluated for pediatric oncology nutrition
decisions. We aimed to develop and pilot test a decision aid to assist parents
making these decisions in collaboration with their healthcare team. MATERIALS AND
METHODS: The decision aid was developed in accordance with the International
Patient Decision Aid Standards guidelines and evaluated in a single-center pilot
study. The parents and healthcare professionals of pediatric oncology patients
were eligible. Participants read the decision aid and completed a questionnaire
assessing acceptability, usability, and improvement in understanding. RESULTS:
Thirty-one parents and 15 healthcare professionals participated. Parents found
the decision aid balanced, relevant, and satisfactory overall. Some parents
reported the decision aid was too long (26%). Healthcare professionals positively
rated the development process, usefulness to parents, and content and format of
the decision aid. Forty-three percent reported that using the decision aid would
save them time. There were no significant associations between health literacy,
decisional satisfaction, decisional regret, acceptability, and improvement in
understanding. CONCLUSION: The decision aid appears acceptable and usable for our
target population. Decision aid feedback provided critical data to make
modifications before evaluating the decision aid in a randomized controlled
trial.
PMID- 27503939
TI - Evaluation of Mitochondrial Respiratory Chain on the Generation of Reactive
Oxygen Species and Cytotoxicity in HaCaT Cells Induced by Nanosized Titanium
Dioxide Under UVA Irradiation.
AB - Nanosized titanium dioxide (nano-TiO2) is widely used in the chemical,
electrical, and electronic industries. Nanosized TiO2 has been reported to be an
efficient photocatalyst, which is able to produce reactive oxygen species (ROS)
under UVA irradiation. In the present work, we evaluate the effect of
mitochondrial respiratory chain on the generation of ROS and cytotoxicity in
keratinocyte (HaCaT) cells induced by nano-TiO2 under UVA irradiation. HaCaT
cells were pretreated with different inhibitors of mitochondrial respiratory
chain and followed by treatment with 200 ug/mL nano-TiO2, then exposed to UVA
(365 nm) for 1 hour and cultured for 24 hours. Our results demonstrated that the
complexes I and III of the mitochondrial respiratory chain are the major site in
the ROS generation induced by nano-TiO2 Our results also demonstrated that the
uncouplers of mitochondrial oxidative phosphorylation resulted in obvious changes
in the production of intracellular ROS induced by nano-TiO2 The ROS sources of
lipoxygenase, cyclooxygenase, and nicotinamide adenine dinucleotide phosphate
oxidase had no significant effect on the ROS production. To some extent, nitric
oxide synthase had effect on the ROS production. These results indicated that
mitochondrial respiratory chain may be the main source of intracellular ROS
production induced by nano-TiO2.
PMID- 27503940
TI - Successful treatment of recurrent pleural and pericardial effusions with
tocilizumab in a patient with systemic lupus erythematous.
AB - A 22-year-old Caucasian man presented to hospital with pleuritic chest pain. He
had had a history of a sun-sensitive rash a year prior. Workup revealed normal
cardiac enzymes and chest X-ray. However, electrocardiogram revealed ST elevation
and PR depression, and echocardiogram revealed a slight pericardial effusion
without other findings. A diagnosis of pericarditis was made. Subsequently, he
was found to be positive for antinuclear antibodies (ANAs), as well as antibodies
to SSA, SSB and double-stranded DNA; C3 was low, and C4 was undetectable. A
diagnosis of systemic lupus erythematosus was made. The patient initially
responded to high-dose ibuprofen. One month later, he developed a new pericardial
effusion, this time with concomitant massive left-sided pleural effusion,
requiring three separate thoracenteses draining a total of 6 L of pleural fluid.
The recurrent effusion failed to respond to high-dose corticosteroid treatment.
Owing to the severity and rapidity of the recurrence of pleural and pericardial
effusion, intravenous tocilizumab was administered. The patient had excellent
clinical and radiographic improvement. This case shows that tocilizumab may have
a role in the treatment of intractable pleuropericardial effusion and other forms
of lupus-associated serositis.
PMID- 27503941
TI - Rare case of gallbladder agenesis presenting with pancreatitis.
AB - Gallbladder agenesis (GA) is a rare congenital abnormality with an incidence of
0.01-0.09%. Majority of GA exist alone although it can be associated with other
systemic malformations involving the gastrointestinal, genitourinary,
cardiovascular and skeletal systems. It is thought that biliary and pancreatic
pathologies coexist and this is the second case reported in the literature of GA
presenting with pancreatitis.
PMID- 27503942
TI - Cerebral venous thrombosis associated with thyrotoxicosis, the use of
desmopressin and elevated factor VIII/von Willebrand factor.
AB - Cerebral venous thrombosis (CVT) is an uncommon disorder associated with diverse
processes. We report a patient who, while receiving desmopressin and
contraceptive pills (OCP), developed straight sinus thrombosis. Clinical
assessment and laboratory investigations revealed untreated hyperthyroidism and a
hypercoagulable state, characterised by high levels of von Willebrand factor,
factor VIII coagulant activity and IgM cardiolipin antibody. The clinical picture
improved with anticoagulation, treatment of hyperthyroidism and discontinuation
of OCP and desmopressin. To the best of our knowledge, the association between
the use of oral desmopressin and CVT has not been described. The multiple risk
factors present in our case were probably additive in increasing the risk of CVT.
Although this case represents a rare occurrence, practitioners should be alerted
to the possible associations of desmopressin, oral contraceptives and Graves'
disease with venous thrombosis.
PMID- 27503943
TI - The importance of gene-environment interactions in human obesity.
AB - The worldwide obesity epidemic has been mainly attributed to lifestyle changes.
However, who becomes obese in an obesity-prone environment is largely determined
by genetic factors. In the last 20 years, important progress has been made in the
elucidation of the genetic architecture of obesity. In parallel with successful
gene identifications, the number of gene-environment interaction (GEI) studies
has grown rapidly. This paper reviews the growing body of evidence supporting
gene-environment interactions in the field of obesity. Heritability, monogenic
and polygenic obesity studies provide converging evidence that obesity
predisposing genes interact with a variety of environmental, lifestyle and
treatment exposures. However, some skepticism remains regarding the validity of
these studies based on several issues, which include statistical modelling,
confounding, low replication rate, underpowered analyses, biological assumptions
and measurement precision. What follows in this review includes (1) an
introduction to the study of GEI, (2) the evidence of GEI in the field of
obesity, (3) an outline of the biological mechanisms that may explain these
interaction effects, (4) methodological challenges associated with GEI studies
and potential solutions, and (5) future directions of GEI research. Thus far,
this growing body of evidence has provided a deeper understanding of GEI
influencing obesity and may have tremendous applications in the emerging field of
personalized medicine and individualized lifestyle recommendations.
PMID- 27503944
TI - Long non-coding RNAs-towards precision medicine in diabetic kidney disease?
AB - Diabetic kidney disease (DKD) is escalating and is the major cause of end stage
kidney failure. There is increasing evidence to support the role of epigenetic
factors and metabolic memory in linking the environmental and genetic causes of
this disease. Although our understanding of this disease has improved, there has
been no significant efficacious therapeutic translation in the last decade.
Current sequencing technology has allowed interrogation of the human
transcriptome. It is evident that although approximately 80% of the genome is
transcribed, only 1-2% is read and coded into protein. The remaining non-coding
RNA, historically assumed to be 'junk', is now known to have key roles in
regulating gene function and orchestrate how and when coding genes are expressed.
This largest subset of non-coding RNAs called long non-coding RNAs (LNCRNAs)
drives epigenetic changes and has functional relevance best characterized in
cancers and cardiovascular disease. This understanding, coupled with the
availability and affordability of RNA sequencing, has shifted our therapeutic
strategies towards genomic therapy in DKD. The role of LNCRNAs with respect to
DKD is only just emerging. In this review we summarize the role of LNCRNAs in DKD
and the existing antisense oligonucleotide therapy that may provide precise and
targeted medicine to treat DKD in this postgenomic era.
PMID- 27503945
TI - Adipose tissue inflammation: a cause or consequence of obesity-related insulin
resistance?
AB - The worldwide obesity epidemic has become a major health concern, because it
contributes to higher mortality due to an increased risk for noncommunicable
diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal
disorders and some cancers. Insulin resistance may link accumulation of adipose
tissue in obesity to metabolic diseases, although the underlying mechanisms are
not completely understood. In the past decades, data from human studies and
transgenic animal models strongly suggested correlative, but also causative
associations between activation of proinflammatory pathways and insulin
resistance. Particularly chronic inflammation in adipose tissue seems to play an
important role in the development of obesity-related insulin resistance. On the
other hand, adipose tissue inflammation has been shown to be essential for
healthy adipose tissue expansion and remodelling. However, whether adipose tissue
inflammation represents a consequence or a cause of impaired insulin sensitivity
remains an open question. A better understanding of the molecular pathways
linking excess adipose tissue storage to chronic inflammation and insulin
resistance may provide the basis for the future development of anti-inflammatory
treatment strategies to improve adverse metabolic consequences of obesity. In
this review, potential mechanisms of adipose tissue inflammation and how adipose
tissue inflammation may cause insulin resistance are discussed.
PMID- 27503946
TI - Energy balance, body composition, sedentariness and appetite regulation: pathways
to obesity.
AB - Energy balance is not a simple algebraic sum of energy expenditure and energy
intake as often depicted in communications. Energy balance is a dynamic process
and there exist reciprocal effects between food intake and energy expenditure. An
important distinction is that of metabolic and behavioural components of energy
expenditure. These components not only contribute to the energy budget directly,
but also by influencing the energy intake side of the equation. It has recently
been demonstrated that resting metabolic rate (RMR) is a potential driver of
energy intake, and evidence is accumulating on the influence of physical activity
(behavioural energy expenditure) on mechanisms of satiety and appetite control.
These effects are associated with changes in leptin and insulin sensitivity, and
in the plasma levels of gastrointestinal (GI) peptides such as glucagon-like
peptide-1 (GLP-1), ghrelin and cholecystokinin (CCK). The influence of fat-free
mass on energy expenditure and as a driver of energy intake directs attention to
molecules emanating from skeletal tissue as potential appetite signals.
Sedentariness (physical inactivity) is positively associated with adiposity and
is proposed to be a source of overconsumption and appetite dysregulation. The
molecular signals underlying these effects are not known but represent a target
for research.
PMID- 27503947
TI - Pro-atherogenic mediators and subclinical atherogenesis are related to epicardial
adipose tissue thickness in patients with cardiovascular risk.
AB - Objective To evaluate the relationship between pro-atherogenic biomarkers and
epicardial adipose tissue (EAT) thickness in patients with cardiovascular risk
factors. Methods Plasma nitric oxide (NO), soluble intercellular adhesion
molecule-1 and malondialdehyde (MDA) levels, EAT thickness, flow-mediated
dilation (FMD) and carotid intima media thickness (CIMT) were determined in
patients aged >18 years who were referred for echocardiography for heart ischemia
or non-ischemic diseases. Cardiovascular risk factors (Framingham score [FS] >=
20) were weighted. Results Hypertension, dyslipidaemia and type 2 diabetes
mellitus were prevalent (>=55% of 40 patients). Patients with FS >= 20 ( n = 21)
showed significantly higher EAT and CIMT values. Globally, MDA, CIMT, age, waist
circumference, high-density lipoprotein cholesterol (HDL-C) and FS were
associated with EAT thickness. EAT was significantly associated with NO in
patients with FS >= 20. Significant differences in EAT thickness were found
between patients stratified by NO value, FMD, age, smoking status, dyslipidaemia,
type 2 diabetes mellitus and FS. An EAT-associated atherogenic risk (CIMT >= 1
mm) model was statistically significant when MDA and type 2 diabetes mellitus
were included. Conclusion EAT thickness was associated with MDA, CIMT, age, waist
circumference, HDL-C and FS globally, but with NO only in patients with FS>=20.
EAT may be used to identify vascular damage stage, possibly influenced by MDA and
type 2 diabetes mellitus.
PMID- 27503948
TI - Integrity of Amygdala Subregion-Based Functional Networks and Emotional Lability
in Drug-Naive Boys With ADHD.
AB - OBJECTIVE: This study evaluated the functional networks of amygdala subregions
(basolateral [BLA], centromedial [CMA], and superficial amygdala [SFA]) in ADHD
and their association with emotional lability (EL) symptoms. METHOD: Resting
state functional connectivity (RSFC) of amygdala subregions and their
correlations with EL scores were evaluated in 35 drug-naive boys with ADHD and 30
age-matched healthy controls (HC). RESULTS: Compared with HC, altered RSFC were
detected differently for each amygdala subregion in ADHD: altered RSFC of BLA
with the thalamus and vermis; aberrant RSFC of CMA with the superior temporal
gyrus/pole and insula, precuneus and cerebellum; reduced RSFC of SFA with dorsal
frontoparietal cortices. Within ADHD, higher EL scores were associated with
reduced negative RSFC of SFA with the dorsolateral prefrontal cortex and inferior
parietal lobe. CONCLUSION: Diffuse alterations of amygdala subregion-based
networks are associated with ADHD, and the weaker SFA-frontoparietal networks
might be involved in the hypothesized top-down effortful regulation of emotion.
PMID- 27503950
TI - Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208.
AB - Aerobic exercise-induced cardiac hypertrophy (CH) is a physiological response
involving accurate orchestration of gene and protein expression of contractile
and metabolic components. The microRNAs: miR-208a, miR-208b and miR-499 are each
encoded by a myosin gene and thus are also known as 'MyomiRs', regulating several
mRNA targets that in turn regulate CH and metabolic pathways. To understand the
role of myomiRs in the fine-tuning of cardiac myosin heavy chain (MHC) isoform
expression by exercise training-induced physiological hypertrophy, Wistar rats
were subjected to two different swim training protocols. We observed that high
volume swim training (T2), improved cardiac diastolic function, induced CH and
decreased the expression of miR-208a and miR-208b Consequently, the increased
expression of their targets, sex determining region y-related transcription
factor 6 (Sox6), Med13, Purbeta, specificity proteins (Sp)/Kruppel-like
transcription factor 3 (SP3) and HP1beta (heterochromatin protein 1beta) was more
prominent in T2, thus converging to modulate cardiac metabolic and contractile
adaptation by exercise training, with an improvement in the alpha-MHC/beta-MHC
ratio, bypassing the increase in PPARbeta and histone deacetylase (HDAC) class I
and II regulation. Altogether, we conclude that high-volume swim training finely
assures physiological cardiac remodelling by epigenetic regulation of myomiRs,
because inhibition of miR-208a and miR-208b increases the expression of their
target proteins and stimulates the interaction among metabolic, contractile and
epigenetic genes.
PMID- 27503949
TI - Administration of tauroursodeoxycholic acid prevents endothelial dysfunction
caused by an oral glucose load.
AB - Postprandial hyperglycaemia leads to a transient impairment in endothelial
function; however, the mechanisms remain largely unknown. Previous work in cell
culture models demonstrate that high glucose results in endoplasmic reticulum
(ER) stress and, in animal studies, ER stress has been implicated as a cause of
endothelial dysfunction. In the present study, we tested the hypothesis that
acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500 mg), a
chemical chaperone known to alleviate ER stress, would prevent hyperglycaemia
induced endothelial dysfunction. In 12 young healthy subjects (seven men, five
women), brachial artery flow-mediated dilation (FMD) was assessed at baseline,
and at 60 and 120 min after an oral glucose challenge. Subjects were tested on
two separate visits in a single-blind randomized cross-over design: after oral
ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during
hyperglycaemia under the placebo condition (-32% at 60 min and -28% at 120 min
post oral glucose load; P<0.05 from baseline) but not under the TUDCA condition (
4% at 60 min and +0.3% at 120 min post oral glucose load; P>0.05 from baseline).
Postprandial plasma glucose and insulin were not altered by TUDCA ingestion.
Plasma oxidative stress markers 3-nitrotyrosine and thiobarbituric acid reactive
substance (TBARS) remained unaltered throughout the oral glucose challenge in
both conditions. These results suggest that hyperglycaemia-induced endothelial
dysfunction can be mitigated by oral administration of TUDCA, thus supporting the
hypothesis that ER stress may contribute to endothelial dysfunction during
postprandial hyperglycaemia.
PMID- 27503951
TI - Basal ganglia necrosis: a 'best-fit' approach.
AB - A previously well 16-year-old boy developed a rapid-onset hypokinetic syndrome,
coupled with a radiological appearance of extensive and highly symmetrical basal
ganglia and white matter change. The diagnostic process was challenging and we
systematically considered potential causes. After excluding common causes of this
clinico-radiological picture, we considered common disorders with this unusual
radiological picture and vice versa, before finally concluding that this was a
rare presentation of a rare disease. We considered the broad categories of:
metabolic; toxic; infective; inflammatory, postinfective and immune-mediated;
neoplastic; paraneoplastic and heredodegenerative. Long-term follow-up gave
insight into the nature of the insult, confirming the monophasic course. During
recovery, and following presumed secondary aberrant reinnervation, his disorder
evolved from predominantly hypokinetic to hyperkinetic. Here, we explore the
process of finding a 'best-fit' diagnosis: in this case, acute necrotising
encephalopathy.
PMID- 27503952
TI - An in silico algorithm for identifying stabilizing pockets in proteins: test
case, the Y220C mutant of the p53 tumor suppressor protein.
AB - The p53 tumor suppressor protein performs a critical role in stimulating
apoptosis and cell cycle arrest in response to oncogenic stress. The function of
p53 can be compromised by mutation, leading to increased risk of cancer;
approximately 50% of cancers are associated with mutations in the p53 gene, the
majority of which are in the core DNA-binding domain. The Y220C mutation of p53,
for example, destabilizes the core domain by 4 kcal/mol, leading to rapid
denaturation and aggregation. The associated loss of tumor suppressor
functionality is associated with approximately 75 000 new cancer cases every
year. Destabilized p53 mutants can be 'rescued' and their function restored;
binding of a small molecule into a pocket on the surface of mutant p53 can
stabilize its wild-type structure and restore its function. Here, we describe an
in silico algorithm for identifying potential rescue pockets, including the
algorithm's integration with the Dynameomics molecular dynamics data warehouse
and the DIVE visual analytics engine. We discuss the results of the application
of the method to the Y220C p53 mutant, entailing finding a putative rescue pocket
through MD simulations followed by an in silico search for stabilizing ligands
that dock into the putative rescue pocket. The top three compounds from this
search were tested experimentally and one of them bound in the pocket, as shown
by nuclear magnetic resonance, and weakly stabilized the mutant.
PMID- 27503953
TI - GADIS: Algorithm for designing sequences to achieve target secondary structure
profiles of intrinsically disordered proteins.
AB - Many intrinsically disordered proteins (IDPs) participate in coupled folding and
binding reactions and form alpha helical structures in their bound complexes.
Alanine, glycine, or proline scanning mutagenesis approaches are often used to
dissect the contributions of intrinsic helicities to coupled folding and binding.
These experiments can yield confounding results because the mutagenesis strategy
changes the amino acid compositions of IDPs. Therefore, an important next step in
mutagenesis-based approaches to mechanistic studies of coupled folding and
binding is the design of sequences that satisfy three major constraints. These
are (i) achieving a target intrinsic alpha helicity profile; (ii) fixing the
positions of residues corresponding to the binding interface; and (iii)
maintaining the native amino acid composition. Here, we report the development of
a G: enetic A: lgorithm for D: esign of I: ntrinsic secondary S: tructure (GADIS)
for designing sequences that satisfy the specified constraints. We describe the
algorithm and present results to demonstrate the applicability of GADIS by
designing sequence variants of the intrinsically disordered PUMA system that
undergoes coupled folding and binding to Mcl-1. Our sequence designs span a range
of intrinsic helicity profiles. The predicted variations in sequence-encoded mean
helicities are tested against experimental measurements.
PMID- 27503954
TI - Conformational dynamics of cancer-associated MyD88-TIR domain mutant L252P
(L265P) allosterically tilts the landscape toward homo-dimerization.
AB - MyD88 is an essential adaptor protein, which mediates the signaling of the toll
like and interleukin-1 receptors' superfamily. The MyD88 L252P (L265P) mutation
has been identified in diffuse large B-cell lymphoma. The identification of this
mutation has been a major advance in the diagnosis of patients with aldenstrom
macroglobulinemia and related lymphoid neoplasms. Here we used computational
methods to characterize the conformational effects of the mutation. Our molecular
dynamics simulations revealed that the mutation allosterically quenched the
global conformational dynamics of the toll/IL-1R (TIR) domain, and readjusted its
salt bridges and dynamic community network. Specifically, the mutation changed
the orientation and reduced the fluctuation of alpha-helix 3, possibly through
eliminating/weakening ~8 salt bridges and enhancing the salt bridge D225-K258.
Using the energy landscape of the TIR domains of MyD88, we identified two dynamic
conformational basins, which correspond to the binding sites used in homo- and
hetero-oligomerization, respectively. Our results indicate that the mutation
stabilizes the core of the homo-dimer interface of the MyD88-TIR domain, and
increases the population of homo-dimer-compatible conformational states in MyD88
family proteins. However, the dampened motion restricts its ability to
heterodimerize with other TIR domains, thereby curtailing physiological
signaling. In conclusion, the L252P both shifts the landscape toward homo
dimerization and restrains the dynamics of the MyD88-TIR domain, which disfavors
its hetero-dimerization with other TIR domains. We further put these observations
within the framework of MyD88-mediated cell signaling.
PMID- 27503955
TI - Disparities, Hospital Financing, And More.
PMID- 27503956
TI - Tackling Disparities With Lessons From Abroad.
AB - Countries endeavoring to reduce health disparities are looking for guidance from
other nations, but challenges abound.
PMID- 27503957
TI - Active Life Expectancy In The Older US Population, 1982-2011: Differences Between
Blacks And Whites Persisted.
AB - Understanding long-range trends in longevity and disability is useful for
projecting the likely impact of the baby-boom generation on long-term care
utilization and spending. We examine changes in active life expectancy in the
United States from 1982 to 2011 for white and black adults ages sixty-five and
older. For whites, longevity increased, disability was postponed to older ages,
the locus of care shifted from nursing facilities to community settings, and the
proportion of life at older ages spent without disability increased. In contrast,
for blacks, longevity increases were accompanied by smaller postponements in
disability, and the percentage of remaining life spent active remained stable and
well below that of whites. Older black women were especially disadvantaged in
2011 in terms of the proportion of years expected to be lived without disability.
Public health measures directed at older black adults-particularly women-are
needed to offset impending pressures on the long-term care delivery system as the
result of population aging.
PMID- 27503958
TI - Sight-Threatening Ocular Diseases Remain Underdiagnosed Among Children Of Less
Affluent Families.
AB - Sight-threatening eye diseases such as strabismus (misaligned eyes) and amblyopia
(lazy eye) develop during childhood. The earlier in life these diseases are
diagnosed and effectively treated, the greater the chance of preventing
irreversible long-term sight loss. Using 2001-14 claims data for nearly 900,000
US children with health insurance, we followed a cohort for up to fourteen years
from birth, to assess whether household net worth affected rates of visits to
ophthalmologists and optometrists or rates of diagnoses of strabismus and
amblyopia. We found considerably lower use of eye care services among children in
less affluent families than among those in more affluent ones, resulting in
estimates of nearly 13,000 missed strabismus diagnoses and over 5,000 missed
amblyopia diagnoses in a ten-year period. Despite ongoing efforts to improve
screening rates for serious childhood ocular disorders, more attention should be
directed to overcoming economic barriers that keep children from obtaining
necessary eye care services.
PMID- 27503959
TI - Using Genetic Technologies To Reduce, Rather Than Widen, Health Disparities.
AB - Evidence shows that both biological and nonbiological factors contribute to
health disparities. Genetics, in particular, plays a part in how common diseases
manifest themselves. Today, unprecedented advances in genetically based diagnoses
and treatments provide opportunities for personalized medicine. However,
disadvantaged groups may lack access to these advances, and treatments based on
research on non-Hispanic whites might not be generalizable to members of minority
groups. Unless genetic technologies become universally accessible, existing
disparities could be widened. Addressing this issue will require integrated
strategies, including expanding genetic research, improving genetic literacy, and
enhancing access to genetic technologies among minority populations in a way that
avoids harms such as stigmatization.
PMID- 27503960
TI - Racial Disparities In Geographic Access To Primary Care In Philadelphia.
AB - Primary care is often thought of as the gateway to improved health outcomes and
can lead to more efficient use of health care resources. Because of primary
care's cardinal importance, adequate access is an important health policy
priority. In densely populated urban areas, spatial access to primary care
providers across neighborhoods is poorly understood. We examined spatial
variation in primary care access in Philadelphia, Pennsylvania. We calculated
ratios of adults per primary care provider for each census tract and included
buffer zones based on prespecified drive times around each tract. We found that
the average ratio was 1,073; the supply of primary care providers varied widely
across census tracts, ranging from 105 to 10,321. We identified six areas of
Philadelphia that have much lower spatial accessibility to primary care relative
to the rest of the city. After adjustment for sociodemographic and insurance
characteristics, the odds of being in a low-access area were twenty-eight times
greater for census tracts with a high proportion of African Americans than in
tracts with a low proportion of African Americans.
PMID- 27503961
TI - Physicians' Participation In ACOs Is Lower In Places With Vulnerable Populations
Than In More Affluent Communities.
AB - Early evidence suggested that accountable care organizations (ACOs) could improve
health care quality while constraining costs, and ACOs are expanding throughout
the United States. However, if disadvantaged patients have unequal access to
physicians who participate in ACOs, that expansion may exacerbate health care
disparities. We examined the relationship between physicians' participation in
both Medicare and commercial ACOs across the country and the sociodemographic
characteristics of their likely patient populations. Physicians' participation in
ACOs varied widely across hospital referral regions, from nearly 0 percent to
over 85 percent. After we adjusted for individual physician and practice
characteristics, we found that physicians who practiced in ZIP Code Tabulation
Areas where a higher percentage of the population was black, living in poverty,
uninsured, or disabled or had less than a high school education-compared to other
areas-had significantly lower rates of ACO participation than other physicians.
Our findings suggest that vulnerable populations' access to physicians
participating in ACOs may not be as great as access for other groups, which could
exacerbate existing disparities in health care quality.
PMID- 27503962
TI - Across US Hospitals, Black Patients Report Comparable Or Better Experiences Than
White Patients.
AB - Patient-reported experience is a critical part of measuring health care quality.
There are limited data on racial differences in patient experience. Using patient
level data for 2009-10 from the Hospital Consumer Assessment of Healthcare
Providers and Systems (HCAHPS), we compared blacks' and whites' responses on
measures of overall hospital rating, communication, clinical processes, and
hospital environment. In unadjusted results, there were no substantive
differences between blacks' and whites' ratings of hospitals. Blacks were less
likely to recommend hospitals but reported more positive experiences, compared to
whites. Higher educational attainment and self-reported worse health status were
associated with more negative evaluations in both races. Additionally, blacks
rated minority-serving hospitals worse than other hospitals on all HCAHPS
measures. Taken together, there were surprisingly few meaningful differences in
patient experience between blacks and whites across US hospitals. Although blacks
tend to receive care at worse-performing hospitals, compared to whites, within
any given hospital black patients tend to report better experience than whites
do.
PMID- 27503963
TI - Language Services In Hospitals Vary By Ownership And Location.
AB - Twenty-four million people in the United States have limited English proficiency.
They experience barriers to health care because of their inability to communicate
effectively with providers. Hospitals are required to provide language services
that reflect the needs of people in their communities, but these services are not
available systematically.
PMID- 27503964
TI - Geographic Concentration Of Home-Based Medical Care Providers.
AB - The United States faces a shortage of providers who care for homebound patients.
About 5,000 primary care providers made 1.7 million home visits to Medicare fee
for-service beneficiaries in 2013, accounting for 70 percent of all home-based
medical visits. Nine percent of these providers performed 44 percent of visits.
However, most homebound people live more than thirty miles from a high-volume
provider.
PMID- 27503965
TI - Achieving Health Equity: Closing The Gaps In Health Care Disparities,
Interventions, And Research.
AB - In the United States, racial/ethnic minority, rural, and low-income populations
continue to experience suboptimal access to and quality of health care despite
decades of recognition of health disparities and policy mandates to eliminate
them. Many health care interventions that were designed to achieve health equity
fall short because of gaps in knowledge and translation. We discuss these gaps
and highlight innovative interventions that help address them, focusing on
cardiovascular disease and cancer. We also provide recommendations for advancing
the field of health equity and informing the implementation and evaluation of
policies that target health disparities through improved access to care and
quality of care.
PMID- 27503967
TI - Strategies To Empower Communities To Reduce Health Disparities.
AB - Community-based participatory research is a promising approach to reducing health
disparities. It empowers individuals and communities to become the major players
in solving their own health problems. We discuss the use of community-based
participatory research and other strategies to enhance empowerment. We also
discuss projects from the Centers for Population Health and Health Disparities
that have empowered communities to achieve positive health outcomes aimed at
reducing disparities. We offer recommendations to policy makers for involving
residents in efforts to achieve health equity.
PMID- 27503966
TI - Evaluating Strategies For Reducing Health Disparities By Addressing The Social
Determinants Of Health.
AB - The opportunities for healthy choices in homes, neighborhoods, schools, and
workplaces can have decisive impacts on health. We review scientific evidence
from promising interventions focused on the social determinants of health and
discuss how such interventions can improve population health and reduce health
disparities. We found sufficient evidence of successful outcomes to support
disparity-reducing policy interventions targeted at education and early
childhood; urban planning and community development; housing; income enhancements
and supplements; and employment. Cost-effectiveness evaluations show that these
interventions lead to long-term societal savings, but the interventions require
more routine attention to cost considerations. We discuss challenges to
implementation, including the need for long-term financing to scale up effective
interventions for implementation at the local, state, and national levels.
PMID- 27503968
TI - Multilevel Interventions To Address Health Disparities Show Promise In Improving
Population Health.
AB - Multilevel interventions are those that affect at least two levels of influence
for example, the patient and the health care provider. They can be experimental
designs or natural experiments caused by changes in policy, such as the
implementation of the Affordable Care Act or local policies. Measuring the
effects of multilevel interventions is challenging, because they allow for
interaction among levels, and the impact of each intervention must be assessed
and translated into practice. We discuss how two projects from the National
Institutes of Health's Centers for Population Health and Health Disparities used
multilevel interventions to reduce health disparities. The interventions, which
focused on the uptake of the human papillomavirus vaccine and community-level
dietary change, had mixed results. The design and implementation of multilevel
interventions are facilitated by input from the community, and more advanced
methods and measures are needed to evaluate the impact of the various levels and
components of such interventions.
PMID- 27503969
TI - Combined Regional Investments Could Substantially Enhance Health System
Performance And Be Financially Affordable.
AB - Leaders across the United States face a difficult challenge choosing among
possible approaches to transform health system performance in their regions. The
ReThink Health Dynamics Model simulates how alternative scenarios could unfold
through 2040. This article compares the likely consequences if four interventions
were enacted in layered combinations in a prototypical midsize US city. We
estimated the effects of efforts to deliver higher-value care; reinvest savings
and expand global payment; enable healthier behaviors; and expand socioeconomic
opportunities. Results suggest that there may be an effective and affordable way
to unlock much greater health and economic potential, ultimately reducing severe
illness by 20 percent, lowering health care costs by 14 percent, and improving
economic productivity by 9 percent. This would require combined investments in
clinical and population-level initiatives, coupled with financial agreements that
reduce incentives for costly care and reinvest a share of the savings to ensure
adequate long-term financing.
PMID- 27503970
TI - Medicare Advantage Plans Pay Hospitals Less Than Traditional Medicare Pays.
AB - There is ongoing debate about how prices paid to providers by Medicare Advantage
plans compare to prices paid by fee-for-service Medicare. We used data from
Medicare and the Health Care Cost Institute to identify the prices paid for
hospital services by fee-for-service (FFS) Medicare, Medicare Advantage plans,
and commercial insurers in 2009 and 2012. We calculated the average price per
admission, and its trend over time, in each of the three types of insurance for
fixed baskets of hospital admissions across metropolitan areas. After accounting
for differences in hospital networks, geographic areas, and case-mix between
Medicare Advantage and FFS Medicare, we found that Medicare Advantage plans paid
5.6 percent less for hospital services than FFS Medicare did. Without taking into
account the narrower networks of Medicare Advantage, the program paid 8.0 percent
less than FFS Medicare. We also found that the rates paid by commercial plans
were much higher than those of either Medicare Advantage or FFS Medicare, and
growing. At least some of this difference comes from the much higher prices that
commercial plans pay for profitable service lines.
PMID- 27503971
TI - The Affordable Care Act's Effects On The Formation, Expansion, And Operation Of
Physician-Owned Hospitals.
AB - The Affordable Care Act (ACA) imposed new restrictions on the formation and
expansion of physician-owned hospitals. These restrictions provided incentives
for the hospitals and their owners to take preemptive actions before the
effective dates of ACA provisions and modify their operations thereafter. We
studied 106 physician-owned hospitals in Texas to determine how they responded to
ACA restrictions. We found that there were significant pre-ACA increases in the
formation, physician ownership, and physical capacity of physician-owned
hospitals, which suggests that they reacted quickly to the policy changes. After
the ACA's provisions took effect, the hospitals improved the use of their assets
to generate increased amounts of services, revenue, and profits. We found no
evidence that existing physician-owned hospitals stopped accepting Medicare to
avoid the ACA restrictions, although some investors adopted a seemingly
unsuccessful strategy of not accepting Medicare at physician-owned hospitals
formed after implementation of the ACA. We conclude that the ACA restrictions
effectively eliminated the formation of new physician-owned hospitals, thus
accomplishing what previous legislative efforts had failed to do.
PMID- 27503972
TI - Accounting For Patients' Socioeconomic Status Does Not Change Hospital
Readmission Rates.
AB - There is an active public debate about whether patients' socioeconomic status
should be included in the readmission measures used to determine penalties in
Medicare's Hospital Readmissions Reduction Program (HRRP). Using the current
Centers for Medicare and Medicaid Services methodology, we compared risk
standardized readmission rates for hospitals caring for high and low proportions
of patients of low socioeconomic status (as defined by their Medicaid status or
neighborhood income). We then calculated risk-standardized readmission rates
after additionally adjusting for patients' socioeconomic status. Our results
demonstrate that hospitals caring for large proportions of patients of low
socioeconomic status have readmission rates similar to those of other hospitals.
Moreover, readmission rates calculated with and without adjustment for patients'
socioeconomic status are highly correlated. Readmission rates of hospitals caring
for patients of low socioeconomic status changed by approximately 0.1 percent
with adjustment for patients' socioeconomic status, and only 3-4 percent fewer
such hospitals reached the threshold for payment penalty in Medicare's HRRP.
Overall, adjustment for socioeconomic status does not change hospital results in
meaningful ways.
PMID- 27503973
TI - Uncompensated Care Decreased At Hospitals In Medicaid Expansion States But Not At
Hospitals In Nonexpansion States.
AB - One pillar of the Affordable Care Act (ACA) was its expected impact on the
growing burden of uncompensated care costs for the uninsured at hospitals.
However, little is known about how this burden changed as a result of the ACA's
enactment. We examine how the Affordable Care Act (ACA)'s coverage expansions
affected uncompensated care costs at a large, diverse sample of hospitals. We
estimate that in states that expanded Medicaid under the ACA, uncompensated care
costs decreased from 4.1 percentage points to 3.1 percentage points of operating
costs. The reductions in Medicaid expansion states were larger at hospitals that
had higher pre-ACA uncompensated care burdens and in markets where we predicted
larger gains in coverage through expanded eligibility for Medicaid. Our estimates
suggest that uncompensated care costs would have decreased from 5.7 percentage
points to 4.0 percentage points of operating costs in nonexpansion states if they
had expanded Medicaid. Thus, while the ACA decreased the variation in
uncompensated care costs across hospitals within Medicaid expansion states, the
difference between expansion and nonexpansion states increased substantially.
Policy makers and researchers should consider how the shifting uncompensated care
burden affects other hospital decisions as well as the distribution of
supplemental public funding to hospitals.
PMID- 27503974
TI - Medicaid Expansion In 2014 Did Not Increase Emergency Department Use But Did
Change Insurance Payer Mix.
AB - In 2014 twenty-eight states and the District of Columbia had expanded Medicaid
eligibility while federal and state-based Marketplaces in every state made
subsidized private health insurance available to qualified individuals. As a
result, about seventeen million previously uninsured Americans gained health
insurance in 2014. Many policy makers had predicted that Medicaid expansion would
lead to greatly increased use of hospital emergency departments (EDs). We
examined the effect of insurance expansion on ED use in 478 hospitals in 36
states during the first year of expansion (2014). In difference-in-differences
analyses, Medicaid expansion increased Medicaid-paid ED visits in those states by
27.1 percent, decreased uninsured visits by 31.4 percent, and decreased privately
insured visits by 6.7 percent during the first year of expansion compared to
nonexpansion states. Overall, however, total ED visits grew by less than 3
percent in 2014 compared to 2012-13, with no significant difference between
expansion and nonexpansion states. Thus, the expansion of Medicaid coverage
strongly affected payer mix but did not significantly affect overall ED use, even
though more people gained insurance coverage in expansion states than in
nonexpansion states. This suggests that expanding Medicaid did not significantly
increase or decrease overall ED visit volume.
PMID- 27503975
TI - Delivering On Accountable Care: Lessons From A Behavioral Health Program To
Improve Access And Outcomes.
AB - Patients with behavioral health disorders often have worse health outcomes and
have higher health care utilization than patients with medical diseases alone. As
such, people with behavioral health conditions are important populations for
accountable care organizations (ACOs) seeking to improve the efficiency of their
delivery systems. However, ACOs have historically faced numerous barriers in
implementing behavioral health population-based programs, including acquiring
reimbursement, recruiting providers, and integrating new services. We developed
an evidence-based, all-payer collaborative care program called Behavioral Health
Associates (BHA), operated as part of UCLA Health, an integrated academic medical
center. Building BHA required several innovations, which included using our
enterprise electronic medical record for behavioral health referrals and
documentation; registering BHA providers with insurance plans' mental health
carve-out products; and embedding BHA providers in primary care practices
throughout the UCLA Health system. Since 2012 BHA has more than tripled the
number of patients receiving behavioral health services through UCLA Health.
After receiving BHA treatment, patients had a 13 percent reduction in emergency
department use. Our efforts can serve as a model for other ACOs seeking to
integrate behavioral health care into routine practice.
PMID- 27503976
TI - Medical Underwriting In Long-Term Care Insurance: Market Conditions Limit Options
For Higher-Risk Consumers.
AB - A key feature of private long-term care insurance is that medical underwriters
screen out would-be buyers who have health conditions that portend near-term
physical or cognitive disability. We applied common underwriting criteria based
on data from two long-term care insurers to a nationally representative sample of
individuals in the target age range (50-71 years) for long-term care insurance.
The screening criteria put upper bounds on the current proportion of Americans
who could gain coverage in the individual market without changes to medical
underwriting practice. Specifically, our simulations show that in the target age
range, approximately 30 percent of those whose wealth meets minimum industry
standards for suitability for long-term care insurance would have their
application for such insurance rejected at the underwriting stage. Among the
general population-without considering financial suitability-we estimated that 40
percent would have their applications rejected. The predicted rejection rates are
substantially higher than the rejection rates of about 20-25 percent of
applicants in the actual market. In evaluating reforms for long-term care
financing and their potential to increase private insurance rates, as well as to
reduce financial pressure on public safety-net programs, policy makers need to
consider the role of underwriting in the market for long-term care insurance.
PMID- 27503977
TI - A Synchronized Prescription Refill Program Improved Medication Adherence.
AB - Synchronizing medication refills-renewing all medications at the same time from
the same pharmacy-is an increasingly popular strategy to improve adherence to
medication regimens, but there has been little research regarding its
effectiveness. In light of increasing policy interest, we evaluated the impact of
a pilot refill synchronization program implemented by a large national insurer. A
random sample of Medicare Advantage patients receiving mail-order refills for
common maintenance medications (antihypertensive, lipid-lowering, or antidiabetic
agents) were invited to join the program and followed for twelve months. On
average, the absolute increase in the proportion of patients deemed adherent
during follow-up was 3-10 percentage points for the intervention group, compared
to 1-5 percentage points for the control group. Patients with poorer baseline
adherence showed larger increases in the absolute proportion deemed adherent in
intervention (23-26 percentage points) compared to a control group (13-15
percentage points). Synchronizing refills might be a promising intervention to
improve adherence to maintenance medications, especially among Medicare patients
with low baseline adherence.
PMID- 27503978
TI - Gaps In Primary Care And Health System Performance In Six Latin American And
Caribbean Countries.
AB - The rapid demographic and epidemiological transitions occurring in Latin America
and the Caribbean have led to high levels of noncommunicable diseases in the
region. In addition to reduced risk factors for chronic conditions, a strong
health system for managing chronic conditions is vital. This study assessed the
extent to which populations in six Latin American and Caribbean countries receive
high-quality primary care, and it examined the relationship between experiences
with care and perceptions of health system performance. We applied a validated
survey on access, use, and satisfaction with health care services to nationally
representative samples of the populations of Brazil, Colombia, El Salvador,
Jamaica, Mexico, and Panama. Respondents reported considerable gaps in the ways
in which primary care is organized, financed, and delivered. Nearly half reported
using the emergency department for a condition they considered treatable in a
primary care setting. Reports of more primary care problems were associated with
worse perceptions of health system performance and quality and less receipt of
preventive care. Urgent attention to primary care performance is required as the
region's population continues to age at an unprecedented rate.
PMID- 27503979
TI - Grasping At The Moon: Enhancing Access To Careers In The Health Professions.
AB - A former HHS secretary reflects on what's needed to enable more minorities to
become doctors and other health professionals.
PMID- 27503980
TI - New Directions For Foundations In Health Equity.
AB - Rising income inequality and pessimism about the current and future status of
race relations in the United States make this both a challenging time for the
pursuit of health equity and also an important opportunity for action. We glean
lessons from past and ongoing philanthropic investments in health equity and
recommend approaches that can guide future work by foundations. Improving health
equity is a complex process that must take into account a variety of factors that
affect health, of which access to high-quality health care is just one element.
Accordingly, improving health equity will require the combined forces of
philanthropy, the public sector, and sectors that have not traditionally been
identified with health.
PMID- 27503982
TI - The Most Profitable US Hospitals.
PMID- 27503983
TI - Profitable Hospitals: The Authors Reply.
PMID- 27503984
TI - The Social Costs Of Lead Poisonings.
PMID- 27503985
TI - Lead Poisonings: The Author Replies.
PMID- 27503986
TI - The Therapeutic Relationship Is Key To Patient Engagement.
PMID- 27503987
TI - Limited Resources For Health: Malaysia And Oman.
PMID- 27503988
TI - Malaysian Health Care System Still Needs Work.
PMID- 27503989
TI - Health Care in Malaysia: The Author Replies.
PMID- 27503991
TI - Medical marijuana research.
PMID- 27503992
TI - Why conscientious objection merits respect.
PMID- 27503993
TI - Are we consistent?
PMID- 27503994
TI - CIHR hikes grants.
PMID- 27503995
TI - Synthetic Biology of Natural Products.
AB - The diversity and natural modularity of their biosynthetic pathways has turned
natural products into attractive, but challenging, targets for synthetic biology
approaches. Here, we discuss the current state of the field, highlighting recent
advances and remaining bottlenecks. Global genomic assessments of natural product
biosynthetic capacities across large parts of microbial diversity provide a first
survey of the available natural parts libraries and identify evolutionary design
rules for further engineering. Methods for compound and pathway detection and
characterization are developed increasingly on the basis of synthetic biology
tools, contributing to an accelerated translation of genomic information into
usable building blocks for pathway assembly. A wide range of methods is also
becoming available for accessing ever larger parts of chemical space by rational
diversification of natural products, guided by rapid progress in our
understanding of the underlying biochemistry and enzymatic mechanisms. Enhanced
genome assembly and editing tools, adapted to the needs of natural products
research, facilitate the realization of ambitious engineering strategies, ranging
from combinatorial library generation to high-throughput optimization of product
titers. Together, these tools and concepts contribute to the emergence of a new
generation of revitalized natural product research.
PMID- 27503996
TI - Polymyxin: Alternative Mechanisms of Action and Resistance.
AB - Antibiotic resistance among pathogenic bacteria is an ever-increasing issue
worldwide. Unfortunately, very little has been achieved in the pharmaceutical
industry to combat this problem. This has led researchers and the medical field
to revisit past drugs that were deemed too toxic for clinical use. In particular,
the cyclic cationic peptides polymyxin B and colistin, which are specific for
Gram-negative bacteria, have been used as "last resort" antimicrobials. Before
the 1980s, these drugs were known for their renal and neural toxicities; however,
new clinical practices and possibly improved manufacturing have made them safer
to use. Previously suggested to primarily attack the membranes of Gram-negative
bacteria and to not easily select for resistant mutants, recent research
exploring resistance and mechanisms of action has provided new perspectives. This
review focuses primarily on the proposed alternative mechanisms of action, known
resistance mechanisms, and how these support the alternative mechanisms of
action.
PMID- 27503997
TI - Somatic TP53 Mutations in the Era of Genome Sequencing.
AB - Amid the complexity of genetic alterations in human cancer, TP53 mutation appears
as an almost invariant component, representing by far the most frequent genetic
alteration overall. Compared with previous targeted sequencing studies, recent
integrated genomics studies offer a less biased view of TP53 mutation patterns,
revealing that >20% of mutations occur outside the DNA-binding domain. Among the
12 mutations representing each at least 1% of all mutations, five occur at
residues directly involved in specific DNA binding, four affect the tertiary fold
of the DNA-binding domain, and three are nonsense mutations, two of them in the
carboxyl terminus. Significant mutations also occur in introns, affecting
alternative splicing events or generating rearrangements (e.g., in intron 1 in
sporadic osteosarcoma). In aggressive cancers, mutation is so common that it may
not have prognostic value (all these cancers have impaired p53 function caused by
mutation or by other mechanisms). In several other cancers, however, mutation
makes a clear difference for prognostication, as, for example, in HER2-enriched
breast cancers and in lung adenocarcinoma with EGFR mutations. Thus, the clinical
significance of TP53 mutation is dependent on tumor subtype and context.
Understanding the clinical impact of mutation will require integrating mutation
specific information (type, frequency, and predicted impact) with data on
haplotypes and on loss of heterozygosity.
PMID- 27503999
TI - Percutaneous mechanical circulatory support: current concepts and future
directions.
PMID- 27503998
TI - Mechanisms of Nucleosome Dynamics In Vivo.
AB - Nucleosomes function to tightly package DNA into chromosomes, but the nucleosomal
landscape becomes disrupted during active processes such as replication,
transcription, and repair. The realization that many proteins responsible for
chromatin regulation are frequently mutated in cancer has drawn attention to
chromatin dynamics; however, the basic mechanisms whereby nucleosomes are
disrupted and reassembled is incompletely understood. Here, I present an overview
of chromatin dynamics as has been elucidated in model organisms, in which our
understanding is most advanced. A basic understanding of chromatin dynamics
during normal developmental processes can provide the context for understanding
how this machinery can go awry during oncogenesis.
PMID- 27504000
TI - The electronic health record as a catalyst for quality improvement in patient
care.
AB - Electronic health records (EHRs) are now broadly used, following decades of
development and incentive programmes for their use. EHRs have been shown through
use of reminders, electronic order sets and other means to improve reliability of
performance of many basic tasks in acute, preventive and chronic care. They
assist with collecting, summarising and displaying the large volumes of
information in patient records and support the implementation of guidelines and
care pathways. Broad use of EHRs has brought into focus weaknesses of the current
generation of EHRs: their user interface, implementation difficulties, time
required to use them and others. Addressing these weaknesses and adopting new
technologies, including use of voice, natural language processing and data
analytic techniques, is necessary for EHRs to achieve their full potential: to
gather information from routine care, to learn from it and to be an integral
component of efforts to continuously improve and to transform care.
PMID- 27504001
TI - Effect of age and aortic valve anatomy on calcification and haemodynamic severity
of aortic stenosis.
AB - OBJECTIVE: To evaluate the effect of age and aortic valve anatomy (tricuspid
(TAV) vs bicuspid (BAV) aortic valve) on the relationship between the aortic
valve calcification (AVC) and the haemodynamic parameters of aortic stenosis (AS)
severity. METHODS: Two hundred patients with AS and preserved left ventricular
ejection fraction were prospectively recruited in the PROGRESSA (Metabolic
Determinants of the Progression of Aortic Stenosis) study and underwent a
comprehensive Doppler echocardiography and multidetector CT (MDCT). Mean
transvalvular gradient (MG) measured by Doppler echocardiography was used to
assess AS haemodynamic severity and AVC was evaluated by MDCT using the Agatston
method and indexed to the left ventricular outflow tract area to obtain AVC
density (AVCd). All analyses were adjusted for sex. RESULTS: Thirty-nine patients
had a BAV and 161 a TAV. Median age was 51 and 72 years for BAV and TAV patients,
respectively. There was a modest correlation between MG and AVCd (rho=0.51,
p<0.0001) in the whole cohort. After dichotomisation for valve anatomy, there was
a good correlation between AVCd and MG in the TAV group (rho=0.61, p<0.0001) but
weak correlation in the BAV group (rho=0.32, p=0.046). In the TAV group, the
strength of the AVCd-MG correlation was similar in younger (<72 years old;
rho=0.59, p<0.0001) versus older (>=72 years old; rho=0.61, p<0.0001) patients.
In the BAV group, there was no correlation between AVCd and MG in younger
patients (<51 years old; rho=0.12, p=0.65), whereas there was a good correlation
in older patients (>=51 years old; rho=0.55, p=0.009). AVCd (p=0.005) and age
(p=0.02) were both independent determinants of MG in BAV patients while AVCd
(p<0.0001) was the only independent determinant of MG in TAV patients.
CONCLUSIONS: In patients with TAV as well as in older patients with BAV, AVCd
appears to be the main factor significantly associated with the haemodynamic
severity of AS and so it may be used to corroborate AS severity in case of
uncertain or discordant findings at echocardiography. However, among younger
patients with BAV, some may have a haemodynamically significant stenosis with
minimal AVCd. The results of MDCT AVCd should thus be interpreted cautiously in
this subset of patients. TRIAL REGISTRATION NUMBER: NCT01679431; Pre-results.
PMID- 27504002
TI - International patterns of dual antiplatelet therapy duration after acute coronary
syndromes.
AB - OBJECTIVE: To describe international patterns of dual antiplatelet therapy (DAPT)
duration after acute coronary syndrome (ACS), and explore its determinants and
correlation with clinical events. METHODS: EPICOR (long-tErm follow-uP of anti
thrombotic management patterns In acute CORonary syndrome patients) is a
prospective, international, observational study of 10 568 ACS hospital survivors
enrolled in 555 centres from 20 countries across Europe and Latin America between
2010 and 2011, with telephone follow-up at quarterly intervals up to 24 months to
assess treatment continuation and clinical events. RESULTS: Of 8593 patients
discharged on DAPT, 4859 (57%) remained on uninterrupted DAPT at end of follow
up. There were minor differences in rates of DAPT discontinuation according to
age, gender, risk factors, therapeutic strategy or region, but major differences
between countries. By study end, 555 of evaluable patients (5.7%) died, 727
(10.0%) experienced new cardiovascular (CV) events, 496 new coronary events
(6.82%) and 154 (2.11%) clinically relevant bleeding (14 (6.7%) fatal). Most CV
events and deaths (85%) occurred while on DAPT. DAPT interruption was associated
with increased risk of CV events in the following week (HR 2.29; 95% CI 1.08 to
4.84) but not specifically with time to first coronary event or mortality.
CONCLUSIONS: Despite guideline recommendations, most patients with ACS in Europe
and Latin America remained on DAPT beyond 12 months, country being the most
important determinant of DAPT duration. Increase in short-term CV risk was seen
after switching from DAPT to less medication, as compared with continued DAPT,
with no long-term effect on coronary or mortality risk. TRIAL REGISTRATION
NUMBER: NCT01171404; Results.
PMID- 27504004
TI - Antithrombotic drug use: scientific breakthroughs, biological limits and
physician behaviour.
PMID- 27504003
TI - Infarct size and left ventricular remodelling after preventive percutaneous
coronary intervention.
AB - OBJECTIVE: We hypothesised that, compared with culprit-only primary percutaneous
coronary intervention (PCI), additional preventive PCI in selected patients with
ST-elevation myocardial infarction with multivessel disease would not be
associated with iatrogenic myocardial infarction, and would be associated with
reductions in left ventricular (LV) volumes in the longer term. METHODS: In the
preventive angioplasty in myocardial infarction trial (PRAMI; ISRCTN73028481),
cardiac magnetic resonance (CMR) was prespecified in two centres and performed
(median, IQR) 3 (1, 5) and 209 (189, 957) days after primary PCI. RESULTS: From
219 enrolled patients in two sites, 84% underwent CMR. 42 (50%) were randomised
to culprit-artery-only PCI and 42 (50%) were randomised to preventive PCI. Follow
up CMR scans were available in 72 (86%) patients. There were two (4.8%) cases of
procedure-related myocardial infarction in the preventive PCI group. The culprit
artery-only group had a higher proportion of anterior myocardial infarctions
(MIs) (55% vs 24%). Infarct sizes (% LV mass) at baseline and follow-up were
similar. At follow-up, there was no difference in LV ejection fraction (%, median
(IQR), (culprit-artery-only PCI vs preventive PCI) 51.7 (42.9, 60.2) vs 54.4
(49.3, 62.8), p=0.23), LV end-diastolic volume (mL/m2, 69.3 (59.4, 79.9) vs 66.1
(54.7, 73.7), p=0.48) and LV end-systolic volume (mL/m2, 31.8 (24.4, 43.0) vs
30.7 (23.0, 36.3), p=0.20). Non-culprit angiographic lesions had low-risk Syntax
scores and 47% had non-complex characteristics. CONCLUSIONS: Compared with
culprit-only PCI, non-infarct-artery MI in the preventive PCI strategy was
uncommon and LV volumes and ejection fraction were similar.
PMID- 27504005
TI - Orthostatic Hypotension in Diabetics in the ACCORD (Action to Control
Cardiovascular Risk in Diabetes) Blood Pressure Trial.
PMID- 27504006
TI - Orthostatic Hypotension in the ACCORD (Action to Control Cardiovascular Risk in
Diabetes) Blood Pressure Trial: Prevalence, Incidence, and Prognostic
Significance.
AB - Orthostatic hypotension (OH) is associated with hypertension and diabetes
mellitus. However, in populations with both hypertension and diabetes mellitus,
its prevalence, the effect of intensive versus standard systolic blood pressure
(BP) targets on incident OH, and its prognostic significance are unclear. In 4266
participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) BP
trial, seated BP was measured 3*, followed by readings every minute for 3 minutes
after standing. Orthostatic BP change, calculated as the minimum standing minus
the mean seated systolic BP and diastolic BP, was assessed at baseline, 12
months, and 48 months. The relationship between OH and clinical outcomes (total
and cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart
failure hospitalization or death and the primary composite outcome of nonfatal
myocardial infarction, nonfatal stroke, and cardiovascular death) was assessed
using proportional hazards analysis. Consensus OH, defined by orthostatic decline
in systolic BP >=20 mm Hg or diastolic BP >=10 mm Hg, occurred at >=1 time point
in 20% of participants. Neither age nor systolic BP treatment target (intensive,
<120 mm Hg versus standard, <140 mm Hg) was related to OH incidence. Over a
median follow-up of 46.9 months, OH was associated with increased risk of total
death (hazard ratio, 1.61; 95% confidence interval, 1.11-2.36) and heart failure
death/hospitalization (hazard ratio, 1.85, 95% confidence interval, 1.17-2.93),
but not with the primary outcome or other prespecified outcomes. In patients with
type 2 diabetes mellitus and hypertension, OH was common, not associated with
intensive versus standard BP treatment goals, and predicted increased mortality
and heart failure events.
PMID- 27504007
TI - Revisiting Fibromuscular Dysplasia: Rationale of the European Fibromuscular
Dysplasia Initiative.
PMID- 27504008
TI - How much does curation cost?
AB - NIH administrators have recently expressed concerns about the cost of curation
for biological databases. However, they did not articulate the exact costs of
curation. Here we calculate the cost of biocuration of articles for the EcoCyc
database as $219 per article over a 5-year period. That cost is 6-15% of the cost
of open-access publication fees for publishing biomedical articles, and we
estimate that cost is 0.088% of the cost of the overall research project that
generated the experimental results. Thus, curation costs are small in an absolute
sense, and represent a miniscule fraction of the cost of the research.
PMID- 27504009
TI - Improving the dictionary lookup approach for disease normalization using enhanced
dictionary and query expansion.
AB - The rapidly increasing biomedical literature calls for the need of an automatic
approach in the recognition and normalization of disease mentions in order to
increase the precision and effectivity of disease based information retrieval. A
variety of methods have been proposed to deal with the problem of disease named
entity recognition and normalization. Among all the proposed methods, conditional
random fields (CRFs) and dictionary lookup method are widely used for named
entity recognition and normalization respectively. We herein developed a CRF
based model to allow automated recognition of disease mentions, and studied the
effect of various techniques in improving the normalization results based on the
dictionary lookup approach. The dataset from the BioCreative V CDR track was used
to report the performance of the developed normalization methods and compare with
other existing dictionary lookup based normalization methods. The best
configuration achieved an F-measure of 0.77 for the disease normalization, which
outperformed the best dictionary lookup based baseline method studied in this
work by an F-measure of 0.13.Database URL:
https://github.com/TCRNBioinformatics/DiseaseExtract.
PMID- 27504010
TI - Crowdsourcing and curation: perspectives from biology and natural language
processing.
AB - Crowdsourcing is increasingly utilized for performing tasks in both natural
language processing and biocuration. Although there have been many applications
of crowdsourcing in these fields, there have been fewer high-level discussions of
the methodology and its applicability to biocuration. This paper explores
crowdsourcing for biocuration through several case studies that highlight
different ways of leveraging 'the crowd'; these raise issues about the kind(s) of
expertise needed, the motivations of participants, and questions related to
feasibility, cost and quality. The paper is an outgrowth of a panel session held
at BioCreative V (Seville, September 9-11, 2015). The session consisted of four
short talks, followed by a discussion. In their talks, the panelists explored the
role of expertise and the potential to improve crowd performance by training; the
challenge of decomposing tasks to make them amenable to crowdsourcing; and the
capture of biological data and metadata through community editing.Database URL:
http://www.mitre.org/publications/technical-papers/crowdsourcing-and-curation
perspectives.
PMID- 27504011
TI - MODEM: multi-omics data envelopment and mining in maize.
AB - MODEM is a comprehensive database of maize multidimensional omics data, including
genomic, transcriptomic, metabolic and phenotypic information from the cellular
to individual plant level. This initial release contains approximately 1.06 M
high quality SNPs for 508 diverse inbred lines obtained by combining variations
from RNA sequencing on whole kernels (15 days after pollination) of 368 lines and
a 50 K array for all 508 individuals. As all of these data were derived from the
same diverse panel of lines, the database also allows various types of genetic
mapping (including characterization of phenotypic QTLs, pQTLs; expression QTLs,
eQTLs and metabolic QTLs, mQTLs). MODEM is thus designed to promote a better
understanding of maize genetic architecture and deep functional annotation of the
complex maize genome (and potentially those of other crop plants) and to explore
the genotype-phenotype relationships and regulation of maize kernel development
at multiple scales, which is also comprehensive for developing novel methods.
MODEM is additionally designed to link with other databases to make full use of
current resources, and it provides visualization tools for easy browsing. All of
the original data and the related mapping results are freely available for easy
query and download. This platform also provides helpful tools for general
analyses and will be continually updated with additional materials, features and
public data related to maize genetics or regulation as they become
available.Database URL: (http://modem.hzau.edu.cn).
PMID- 27504012
TI - FNDC5 Alleviates Hepatosteatosis by Restoring AMPK/mTOR-Mediated Autophagy, Fatty
Acid Oxidation, and Lipogenesis in Mice.
AB - Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of
subcutaneous fat and mediates the beneficial effects of exercise on metabolism.
However, whether FNDC5 is associated with hepatic steatosis, autophagy, fatty
acid oxidation (FAO), and lipogenesis remains unknown. Herein, we show the roles
and mechanisms of FNDC5 in hepatic steatosis, autophagy, and lipid metabolism.
Fasted FNDC5-/- mice exhibited severe steatosis, reduced autophagy, and FAO, and
enhanced lipogenesis in the liver compared with wild-type mice. Energy
deprivation-induced autophagy, FAO, and AMPK activity were attenuated in FNDC5-/-
hepatocytes, which were restored by activating AMPK with 5-aminoimidazole-4
carboxamide ribonucleotide (AICAR). Inhibition of mammalian target of rapamycin
(mTOR) complex 1 with rapamycin enhanced autophagy and FAO and attenuated
lipogenesis and steatosis in FNDC5-/- livers. FNDC5 deficiency exacerbated
hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and
lipid accumulation in obese mice. Exogenous FNDC5 stimulated autophagy and FAO
gene expression in hepatocytes and repaired the attenuated autophagy and
palmitate-induced steatosis in FNDC5-/- hepatocytes. FNDC5 overexpression
prevented hyperlipemia, hepatic FAO and autophagy impairment, hepatic
lipogenesis, and lipid accumulation in obese mice. These results indicate that
FNDC5 deficiency impairs autophagy and FAO and enhances lipogenesis via the
AMPK/mTOR pathway. FNDC5 deficiency aggravates whereas FNDC5 overexpression
prevents the HFD-induced hyperlipemia, hepatic lipid accumulation, and impaired
FAO and autophagy in the liver.
PMID- 27504013
TI - Insulin Resistance Is Accompanied by Increased Fasting Glucagon and Delayed
Glucagon Suppression in Individuals With Normal and Impaired Glucose Regulation.
AB - Hyperinsulinemia is an adaptive mechanism that enables the maintenance of
normoglycemia in the presence of insulin resistance. We assessed whether glucagon
is also involved in the adaptation to insulin resistance. A total of 1,437
individuals underwent an oral glucose tolerance test with measurements of
circulating glucose, insulin, and glucagon concentrations at 0, 30 and 120 min.
Early glucagon suppression was defined as suppression in the period from 0 to 30
min, and late glucagon suppression as 30 to 120 min after glucose intake. Insulin
sensitivity was estimated by the validated insulin sensitivity index. Individuals
with screen-detected diabetes had 30% higher fasting glucagon levels and
diminished early glucagon suppression, but greater late glucagon suppression when
compared with individuals with normal glucose tolerance (P <= 0.014). Higher
insulin resistance was associated with higher fasting glucagon levels, less early
glucagon suppression, and greater late glucagon suppression (P < 0.001). The
relationship between insulin sensitivity and fasting glucagon concentrations was
nonlinear (P < 0.001). In conclusion, increased fasting glucagon levels and
delayed glucagon suppression, together with increased circulating insulin levels,
develop in parallel with insulin resistance. Therefore, glucose maintenance
during insulin resistance may depend not only on hyperinsulinemia but also on the
ability to suppress glucagon early after glucose intake.
PMID- 27504014
TI - The Stepwise Approach to Diabetes Prevention: Results From the D-CLIP Randomized
Controlled Trial.
AB - OBJECTIVE: This study tests the effectiveness of expert guidelines for diabetes
prevention: lifestyle intervention with addition of metformin, when required,
among people with prediabetes. RESEARCH DESIGN AND METHODS: The Diabetes
Community Lifestyle Improvement Program (D-CLIP) is a randomized, controlled,
translation trial of 578 overweight/obese Asian Indian adults with isolated
impaired glucose tolerance (iIGT), isolated impaired fasting glucose (iIFG), or
IFG+IGT in Chennai, India. Eligible individuals were identified through community
based recruitment and randomized to standard lifestyle advice (control) or a 6
month, culturally tailored, U.S. Diabetes Prevention Program-based lifestyle
curriculum plus stepwise addition of metformin (500 mg, twice daily) for
participants at highest risk of conversion to diabetes at >=4 months of follow
up. The primary outcome, diabetes incidence, was assessed biannually and compared
across study arms using an intention-to-treat analysis. RESULTS: During 3 years
of follow-up, 34.9% of control and 25.7% of intervention participants developed
diabetes (P = 0.014); the relative risk reduction (RRR) was 32% (95% CI 7-50),
and the number needed to treat to prevent one case of diabetes was 9.8. The RRR
varied by prediabetes type (IFG+IGT, 36%; iIGT, 31%; iIFG, 12%; P = 0.77) and was
stronger in participants 50 years or older, male, or obese. Most participants
(72.0%) required metformin in addition to lifestyle, although there was
variability by prediabetes type (iIFG, 76.5%; IFG+IGT, 83.0%; iIGT, 51.3%).
CONCLUSIONS: Stepwise diabetes prevention in people with prediabetes can
effectively reduce diabetes incidence by a third in community settings; however,
people with iIFG may require different interventions.
PMID- 27504015
TI - Expression of Organic Anion Transporting Polypeptide 1A2 in Red Blood Cells and
Its Potential Impact on Antimalarial Therapy.
AB - Important antimalarial drugs, including quinolines, act against blood schizonts
by interfering with hemoglobin metabolism. To reach their site of action, these
compounds have to cross the plasma membrane of red blood cells (RBCs). Organic
cation transporters (OCTs) and organic anion transporting polypeptides (OATPs)
are important uptake transporters and interesting candidates for local drug
transport. We therefore studied their interaction with antimalarial compounds
(quinine, chloroquine, mefloquine, pyrimethamine, artemisinin, and artesunate)
and characterized the expression of OATP1A2 and OATP2B1 in RBCs. Competition
assays using transporter-overexpressing Madin-Darby canine kidney (MDCKII) cells
and the model substrate estrone-3-sulfate identified quinine and chloroquine as
potent inhibitors of OATP1A2 function (IC50 quinine: 0.7 +/- 1.2 uM; chloroquine:
1.0 +/- 1.5 uM), but no or only moderate effects were observed for OATP2B1.
Subsequently, quinine was identified as a substrate of OATP1A2 (Km 23.4 uM). The
OATP1A2-mediated uptake was sensitive to the OATP1A2-specific inhibitor naringin.
Both OATPs were expressed in human RBCs, and ex vivo transport studies
demonstrated naringin-sensitive accumulation of quinine in these cells (60 pmol
versus 38 pmol/5 * 10(5) RBCs). Additional transport studies using OCT1-3 and
organic cation transporter novel type 1 (OCTN1) indicated only significant
quinine uptake by OCT1, which was not detected in RBCs. In conclusion, our data
demonstrate expression of OATP2B1 and OATP1A2 in RBCs as well as OATP1A2-mediated
uptake of quinine. Therefore, modulation of OATP1A2 function may affect quinine
uptake into erythrocytes.
PMID- 27504016
TI - In Vitro and In Vivo Drug-Drug Interaction Studies to Assess the Effect of
Abiraterone Acetate, Abiraterone, and Metabolites of Abiraterone on CYP2C8
Activity.
AB - Abiraterone acetate, the prodrug of the cytochrome P450 C17 inhibitor
abiraterone, plus prednisone is approved for treatment of metastatic castration
resistant prostate cancer. We explored whether abiraterone interacts with drugs
metabolized by CYP2C8, an enzyme responsible for the metabolism of many drugs.
Abiraterone acetate and abiraterone and its major metabolites, abiraterone
sulfate and abiraterone sulfate N-oxide, inhibited CYP2C8 in human liver
microsomes, with IC50 values near or below the peak total concentrations observed
in patients with metastatic castration-resistant prostate cancer (IC50 values:
1.3-3.0 uM, 1.6-2.9 uM, 0.044-0.15 uM, and 5.4-5.9 uM, respectively). CYP2C8
inhibition was reversible and time-independent. To explore the clinical relevance
of the in vitro data, an open-label, single-center study was conducted comprising
16 healthy male subjects who received a single 15-mg dose of the CYP2C8 substrate
pioglitazone on day 1 and again 1 hour after the administration of abiraterone
acetate 1000 mg on day 8. Plasma concentrations of pioglitazone, its active M-III
(keto derivative) and M-IV (hydroxyl derivative) metabolites, and abiraterone
were determined for up to 72 hours after each dose. Abiraterone acetate increased
exposure to pioglitazone; the geometric mean ratio (day 8/day 1) was 125 [90%
confidence interval (CI), 99.9-156] for Cmax and 146 (90% CI, 126-171) for
AUClast Exposure to M-III and M-IV was reduced by 10% to 13%. Plasma abiraterone
concentrations were consistent with previous studies. These results show that
abiraterone only weakly inhibits CYP2C8 in vivo.
PMID- 27504017
TI - The role of cell-free circulating microRNA in diagnostics in patients with
rheumatoid arthritis.
PMID- 27504018
TI - Antibody profile to Borrelia burgdorferi in veterinarians from Nuevo Leon,
Mexico, a non-endemic area of this zoonosis.
AB - OBJECTIVES: Lyme disease is a tick-borne disease caused by infections with
Borrelia. Persons infected with Borrelia can be asymptomatic or can develop
disseminated disease. Diagnosis and recognition of groups at risk of infection
with Borrelia burgdorferi is of great interest to contemporary rheumatology.
There are a few reports about Borrelia infection in Mexico, including
lymphocytoma cases positive to B. burgdorferi sensu stricto by PCR and a patient
with acrodermatitis chronica atrophicans. Veterinarians have an occupational risk
due to high rates of tick contact. The aim of this work was to investigate
antibodies to Borrelia in students at the Faculty of Veterinary Medicine and
Zootechnics, at Nuevo Leon, Mexico, and determine the antibody profile to B.
burgdorferi antigens. MATERIAL AND METHODS: Sera were screened using a C6 ELISA,
IgG and IgM ELISA using recombinant proteins from B. burgdorferi, B. garinii and
B. afzelii. Sera with positive or grey-zone values were tested by IgG Western
blot to B. burgdorferi sensu stricto. RESULTS: All volunteers reported tick
exposures and 72.5% remembered tick bites. Only nine persons described mild Lyme
disease related symptoms, including headaches, paresthesias, myalgias and
arthralgias. None of the volunteers reported erythema migrans. Nine samples were
confirmed by IgG Western blot. The profile showed 89% reactivity to OspA, 67% to
p83, and 45% to BmpA. CONCLUSIONS: Positive sera samples shared antibody
reactivity to the markers of late immune response p83 and BmpA, even if
individuals did not present symptoms of Lyme arthritis or post-Lyme disease. The
best criterion to diagnose Lyme disease in our country remains to be established,
because it is probable that different strains coexist in Mexico. This is the
first report of antibodies to B. burgdorferi in Latin American veterinarians.
Veterinarians and high-risk people should be alert to take precautionary measures
to prevent tick-borne diseases.
PMID- 27504019
TI - Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes
cultured in synovial fluid isolated from patients with rheumatoid arthritis.
AB - OBJECTIVES: Leptin is an adipose cells derived hormone that regulates energy
homeostasis within the body. Energy metabolism of immune cells influences their
activity within numerous pathological states, but the effect of leptin on these
cells in unclear. On the one hand, it was observed that leptin induces
neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils
exposed to leptin did not display detectable Ca(2+) ions mobilization or beta2
integrin upregulation. In this study, we investigated the effect of leptin on the
redox homeostasis in lymphocytes and neutrophils. MATERIAL AND METHODS:
Neutrophils and lymphocytes were isolated by density-gradient centrifugation of
blood from healthy volunteers. Cells were cultured with or without leptin (100
ng/ml for lymphocytes and 500 ng/ml for neutrophils) or with or without synovial
fluid (85%) for 0-72 h. Culture media were not changed during incubation. Cells
were homogenized and homogenate was frozen until laboratory measurements. Redox
homeostasis was assessed by the reduced glutathione (GSH) vs. oxidized
glutathione (GSSG) ratio and membrane lipid peroxidation evaluation. RESULTS:
Lymphocytes cultured with leptin and synovial fluid showed a significant increase
of the GSSG level. The GSSG/GSH ratio increased by 184 +/-37%. In neutrophils
incubated in a similar environment, the GSSG/GSH ratio increased by just 21 +/
7%, and the effect was observed irrespectively of whether they were exposed to
leptin or synovial fluid or both together. Neither leptin nor synovial fluid
influenced lipid peroxidation in neutrophils, but in lymphocytes leptin
intensified lipid peroxidation. CONCLUSIONS: Leptin altered the lymphocytes, but
not neutrophils redox state. Because firstly neutrophils are anaerobic cells and
have just a few mitochondria and secondly lymphocytes have typical aerobic
metabolism, the divergence of our data supports the hypothesis that leptin
induces oxidative stress by modulation of mitochondria.
PMID- 27504020
TI - Radionuclide synovectomy - essentials for rheumatologists.
AB - Radionuclide synovectomy is a minimally invasive method of treating persistent
joint inflammation. It involves intra-articular injection of radioactive colloids
which induce necrosis and fibrosis of hypertrophic synovial membrane. The most
common indication for radiosynovectomy is rheumatoid arthritis, although patients
with seronegative spondyloarthropathies, unclassified arthritis, haemophilic
arthropathy and other less common arthropathies can also benefit from this
method. Radiosynovectomy is safe, well tolerated and efficacious. About 70-80% of
patients respond well to the therapy. However, the therapeutic effects are
considerably worse in patients with co-existent osteoarthritis and advanced joint
degeneration. Despite its advantages, radionuclide synovectomy is not performed
as often as it could be, so greater knowledge and understanding of this method
are needed. The authors present the most important facts about radiosynovectomy
that may help rheumatologists in their daily clinical practice.
PMID- 27504021
TI - Physical activity in the elderly who underwent joint replacement surgery in the
course of rheumatic diseases.
AB - According to the forecasts of the Central Statistical Office of Poland, in 2030
people at the age of 65 and older will account for 23.8%, i.e. their number will
amount to approx. 8.5 m people. Geriatric rheumatic patients more often decide to
undergo surgical joint replacement. According to the National Health Fund, the
number of joint replacement services provided in 2014 increased by 93%, as
compared to 2005. Improving the physical performance of this constantly expanding
group of patients requires taking into account many factors to raise their
functional status, reduce the risk of falling, teach rules of proper functioning
with an artificial joint and encourage unassisted physical activity. Restoring
fitness and independence is a difficult but necessary task due to an increasing
number of seniors with replaced joint.
PMID- 27504022
TI - Rheumatic diseases induced by drugs and environmental factors: the state-of-the
art - part one.
AB - The majority of rheumatic diseases belong to the group of autoimmune diseases and
are associated with autoantibody production. Their etiology is not fully
understood. Certain medications and environmental factors may have an influence
on the occurrence of rheumatic diseases. Establishing a cause-effect relationship
between a certain factor and disease induction is not always simple. It is
important to administer the drug continuously or monitor exposure to a given
factor in the period preceding the onset of symptoms. The lack of previously
diagnosed autoimmune disease, or finally the lack of symptoms within a few
weeks/months after discontinuation of the drug/cessation of exposure, is also
important. The most frequently mentioned rheumatic diseases caused by drugs and
environmental factors include systemic lupus erythematosus, scleroderma, systemic
vasculitis, polymyositis, dermatomyositis, and Sjogren's syndrome. The objective
of this study is to summarize current knowledge on rheumatic diseases induced by
drugs and environmental factors.
PMID- 27504023
TI - Cardiovascular risk assessment in rheumatoid arthritis - controversies and the
new approach.
AB - The current methods of cardiovascular (CV) risk assessment in the course of
inflammatory connective tissue diseases are a subject of considerable
controversy. Comparing different methods of CV risk assessment in current
rheumatoid arthritis (RA) guidelines, only a few of them recommend the use of
formal risk calculators. These are the EULAR guidelines suggesting the use of
SCORE and the British Society for Rheumatology guidelines performed in
collaboration with NICE preferring the use of QRISK-2. Analyzing the latest
American and British reports, two main concepts could be identified. The first
one is to focus on risk calculators developed for the general population taking
into account RA, and the calculator that might fulfill this role is the new QRISK
2 presented by NICE in 2014. The second concept is to create RA-specific risk
calculators, such as the Expanded Cardiovascular Risk Prediction Score for RA. In
this review we also discuss the efficiency of a new Pooled Cohort Equation and
other calculators in the general and RA population.
PMID- 27504024
TI - Pachydermodactyly - a report of two cases.
AB - Pachydermodactyly (PDD) is a rare and benign form of digital soft tissues
fibromatosis, which affects the skin of the fingers. The disorder is
characterized by asymptomatic, symmetric, progressive soft tissue swelling of the
proximal interphalangeal (PIP) joints of the fingers. The etiology of disease
remains unknown. It is usually acquired, even though there are some publications
that document family cases. It affects mainly adolescent men. We report two boys
with the bilateral swelling of the of the PIP joints of the fingers and skin and
subcutaneous tissue thickening. Based on clinical manifestations, radiological
study and histopathological examination, pachydermodactyly was diagnosed. PDD is
a rare and benign disorder, although it is important to consider other diseases,
especially rheumatic conditions, in the differential diagnosis in order to avoid
unnecessary additional tests and treatments.
PMID- 27504025
TI - The paediatric rheumatologist and orphan disease - a story without happy ending.
AB - Orphan diseases are not a common challenge in the everyday practice of the
rheumatologist. Despite their extremely rare occurrence one of the patients under
our care developed one of them - neuronal ceroid lipofuscinosis, the most
frequent neurodegenerative disease observed in the paediatric population. We
report a case of 2-year-old girl diagnosed with oligoarticular form of juvenile
idiopathic arthritis treated in our Department with steroids and methotrexate and
staying in the stage of disease remission. During routine checkups at Outpatient
Clinic we observed progressive deterioration of girls neurological condition
resulting in ataxia, gait disturbances with no rheumatological cause behind and
speech impairment. The appearance of the symptoms was accompanied by frequent
episodes of epileptic seizures, with little clinical improvement on combined
antiepileptic treatment. Magnetic resonance imaging that we performed showed a
picture highly suggestive of neuronal ceroid lipofuscinosis - atrophy of the
patients cerebrum and cerebellum. Genetic testing conducted resulted in the
diagnosis of late infantile neuronal ceroid lipofuscinosis (LINCL).
PMID- 27504026
TI - Rivaroxaban - a safe therapeutic option in patients with antiphospholipid
syndrome? Our experience in 23 cases.
AB - In the therapeutic approach to patients with antiphospholipid syndrome (APS) with
thrombotic manifestations, oral vitamin K antagonists (VKA) remain the standard
of care. However, the use of VKA is very often associated with inability to
achieve a therapeutic dose even in patients maintaining nutritional and
therapeutic restrictions. The non-vitamin-K oral anticoagulants (NOAC) have a lot
of advantages, but their efficacy and safety in APS have not been proven. We
present 23 patients with APS treated with rivaroxaban in our department.
Recurrence of thrombosis was observed only in 1 patient. No major or minor
bleeding occurred. It proves the efficacy of treatment with rivaroxaban, but our
observations require further prospective, randomized studies.
PMID- 27504027
TI - The role of melanin pathways in extremotolerance and virulence of Fonsecaea
revealed by de novo assembly transcriptomics using illumina paired-end
sequencing.
AB - Melanisation has been considered to be an important virulence factor of Fonsecaea
monophora. However, the biosynthetic mechanisms of melanisation remain unknown.
We therefore used next generation sequencing technology to investigate the
transcriptome and digital gene expression data, which are valuable resources to
better understand the molecular and biological mechanisms regulating melanisation
in F. monophora. We performed de novo transcriptome assembly and digital gene
expression (DGE) profiling analyses of parent (CBS 122845) and albino (CBS
125194) strains using the Illumina RNA-seq system. A total of 17 352 annotated
unigenes were found by BLAST search of NR, Swiss-Prot, Gene Ontology, Clusters of
Orthologous Groups and Kyoto Encyclopedia of Genes and Genomes (KEGG) (E-value
<1e-5). A total of 2 283 unigenes were judged to be the differentially expressed
between the two genotypes. We identified most of the genes coding for key enzymes
involved in melanin biosynthesis pathways, including polyketide synthase (pks),
multicopper oxidase (mco), laccase, tyrosinase and homogentisate 1,2-dioxygenase
(hmgA). DEG analysis showed extensive down-regulation of key genes in the DHN
pathway, while up-regulation was noted in the DOPA pathway of the albino mutant.
The transcript levels of partial genes were confirmed by real time RT-PCR, while
the crucial role of key enzymes was confirmed by either inhibitor or substrate
tests in vitro. Meanwhile, numbers of genes involved in light sensing, cell wall
synthesis, morphology and environmental stress were identified in the
transcriptome of F. monophora. In addition, 3 353 SSRs (Simple Sequence Repeats)
markers were identified from 21 600 consensus sequences. Blocking of the DNH
pathway is the most likely reason of melanin deficiency in the albino strain,
while the production of pheomelanin and pyomelanin were probably regulated by
unknown transcription factors on upstream of both pathways. Most of genes
involved in environmental tolerance to oxidants, irradiation and extreme
temperatures were also assembled and annotated in transcriptomes of F. monophora.
In addition, thousands of identified cSSR (combined SSR) markers will favour
further genetic linkage studies. In conclusion, these data will contribute to
understanding the regulation of melanin biosynthesis and help to improve the
studies of pathogenicity of F. monophora.
PMID- 27504028
TI - Take-all or nothing.
AB - Take-all disease of Poaceae is caused by Gaeumannomyces graminis
(Magnaporthaceae). Four varieties are recognised in G. graminis based on
ascospore size, hyphopodial morphology and host preference. The aim of the
present study was to clarify boundaries among species and varieties in
Gaeumannomyces by combining morphology and multi-locus phylogenetic analyses
based on partial gene sequences of ITS, LSU, tef1 and rpb1. Two new genera,
Falciphoriella and Gaeumannomycella were subsequently introduced in
Magnaporthaceae. The resulting phylogeny revealed several cryptic species
previously overlooked within Gaeumannomyces. Isolates of Gaeumannomyces were
distributed in four main clades, from which 19 species could be delimited, 12 of
which were new to science. Our results show that the former varieties
Gaeumannomyces graminis var. avenae and Gaeumannomyces graminis var. tritici
represent species phylogenetically distinct from G. graminis, for which the new
combinations G. avenae and G. tritici are introduced. Based on molecular data,
morphology and host preferences, Gaeumannomyces graminis var. maydis is proposed
as a synonym of G. radicicola. Furthermore, an epitype for Gaeumannomyces
graminis var. avenae was designated to help stabilise the application of that
name.
PMID- 27504029
TI - Active Patient Engagement: Long Overdue in Rehabilitation Research.
PMID- 27504030
TI - Association between Neuropathic Pain and Reported Disability after Total Knee
Arthroplasty.
AB - PURPOSE: To determine whether reporting neuropathic pain (NP) at an average of 5
years after total knee arthroplasty (TKA) was related to patient age, sex,
preoperative comorbidity, arthritis self-efficacy, or disability before surgery
and at 1 year after surgery. The estimate of NP prevalence and cross-sectional
group differences were explored at 5 years after surgery. METHODS: A subsample of
participants in a formal research study was contacted via mail approximately 5
years after undergoing surgery and were sent four questionnaires: the Western
Ontario and McMaster Universities Osteoarthritis Index, the Patient Health
Questionnaire, the Self-Administered Leeds Assessment of Neuropathic Signs and
Symptoms (S-LANSS), and a satisfaction questionnaire. NP was defined as an S
LANSS score of 12 or more. RESULTS: Of 89 patients who met the inclusion
criteria, data for 63 (71%) patients (47 women; mean age 67 [SD 8] y) were used
for analysis. Of these 63, 9 (14%) were identified as having NP. None had a
report of failure of prosthesis or other surgical complications according to most
recent medical records. There was no relationship between preoperative patient
characteristics and development of NP. However, the NP group on average had a
higher report of stiffness (p=0.020), physical dysfunction (p=0.019), and pain
(p=0.050) at 1 year after surgery. Cross-sectional comparisons showed higher
levels of pain (p=0.001), stiffness (p=0.008), physical dysfunction (p=0.003),
and depression (p=0.005) and lower satisfaction (p=0.018) at the time of the
survey than the patients without NP. CONCLUSION: The estimated prevalence of NP
was 14%. Patients with NP reported higher levels of disability as early as 1 year
after surgery. They remained more disabled, with a higher level of depression and
less satisfaction, at an average of 5 years after surgery.
PMID- 27504031
TI - Effects of Autogenic Drainage on Sputum Recovery and Pulmonary Function in People
with Cystic Fibrosis: A Systematic Review.
AB - PURPOSE: To determine the effects of short- and long-term use of autogenic
drainage (AD) on pulmonary function and sputum recovery in people with cystic
fibrosis (CF). METHODS: The authors conducted a systematic review of randomized
and quasi-randomized clinical trials in which participants were people with CF
who use AD as their sole airway clearance technique. RESULTS: Searches in 4
databases and secondary sources using 5 key terms yielded 735 articles, of which
58 contained the terms autogenic drainage and cystic fibrosis. Ultimately, 4
studies, 2 of which were long term, were included. All measured forced expiratory
volume in 1 second (FEV1) and found no change. The long-term studies were
underpowered to detect change in FEV1; however, the short-term studies found a
clinically significant sputum yield (>=4 g). CONCLUSION: AD has been shown to
produce clinically significant sputum yields in a limited number of
investigations. The effect of AD on the function of the pulmonary system remains
uncertain, and questions have emerged regarding the appropriateness of FEV1 as a
valid measure of airway clearance from peripheral lung regions. Further
consideration should be given to the use of FEV1 as a primary measure of the
effect of AD.
PMID- 27504032
TI - Factors Affecting Length of Stay in Adult Outpatient Physical Rehabilitation: A
Scoping Review of the Literature.
AB - PURPOSE: To identify factors affecting length of stay (LOS) for adults
participating in outpatient physical or occupational therapy programmes. METHOD:
A scoping review of the literature was conducted using the Ovid MEDLINE, EMBASE,
CINAHL, AMED, and Cochrane Library databases. RESULTS: A total of 19 articles
were retained from the search, and 2 additional articles were retrieved from grey
literature (i.e., non-published sources). Personal factors affecting LOS are age
and sex, both of which had inconsistent effects on LOS, and communication,
language, physical, and cognitive difficulties, for which higher levels of
function were generally associated with shorter LOS. Institutional factors
affecting LOS were location, interdisciplinary communication, number of
disciplines involved, and type of rehabilitation setting. Finally, two clinician
related factors-fewer treatment goals and a selection of evidence-informed
treatment techniques-were associated with shorter LOS. CONCLUSIONS: Research on
factors affecting adult outpatient rehabilitation LOS is limited and
inconsistent. A preliminary list of LOS factors was produced, but this topic
should be further explored with the collaboration of researchers and clinical
institutions.
PMID- 27504033
TI - What Makes a Leader: Identifying the Strengths of Canadian Physical Therapists.
AB - PURPOSE: To identify the personal strengths of Canadian physical therapists who
hold leadership positions and compare them with the strengths of Canadian
physical therapists who do not occupy positions of leadership. METHODS: A
quantitative, cross-sectional online survey was distributed to registered
Canadian physical therapists. We used the Clifton StrengthsFinder to evaluate 34
characteristics and determine which characteristics described a participant's
strengths. Population demographics and leadership strengths were described via
frequency distributions and percentages; chi-square analyses and Fisher's exact
tests were used to compare differences between groups. RESULTS: Of 173 physical
therapists who completed the survey, 108 occupied a position of leadership, and
65 did not. Those in the leader group had significantly more experience and
achieved a higher level of education. Leaders most frequently exhibited the
strengths of learner, achiever, responsibility, input, and strategic, whereas non
leaders most frequently displayed strengths of learner, achiever, input, relator,
and harmony. Leaders were significantly more likely than non-leaders to possess
the achiever strength. Gender, level of education, and years of experience did
not significantly influence which strengths were present in the leadership
profile. CONCLUSIONS: There is substantial overlap between leaders and non
leaders in terms of leadership profiles. Future research should investigate
whether leadership strengths vary depending on the leadership position occupied
and whether leadership development initiatives promote leadership strengths.
PMID- 27504034
TI - The Group Experience: Remodelling Outpatient Physiotherapy after Knee Replacement
Surgery.
AB - Purpose : To estimate responses to short-duration (4-6 weeks) group-based
physiotherapy after knee replacement in terms of pain, function, and
satisfaction. METHOD: The study used a prospective, observational design. A total
of 169 participants (111 women, 58 men) were consecutively recruited to attend a
twice-weekly post-operative knee replacement class focused on mobility, strength,
balance, and functional retraining. Changes in pain, function, and satisfaction
were measured using the P4 pain intensity measure, the Lower Extremity Functional
Scale (LEFS), a timed stair test (TST), knee range of motion (ROM), the Patient
Specific Functional Scale (PSFS), and the Client Satisfaction Questionnaire (CSQ
8). Using Stata version 12.1, the data were summarized descriptively, and change
scores were calculated with 95% CIs. Results : On average, participants were
discharged within 11 classes, having achieved their treatment goals. More than
77% exceeded the minimal detectable change at the 90% confidence level (MDC90) on
the LEFS, TST, PSFS, and ROM assessments. The mean CSQ-8 score at discharge was
31.8 (SD 1.46); 66.7% recorded a perfect score of 32. Conclusions : Patients
attending a short group-based outpatient knee replacement class demonstrated
significant improvements in pain and lower extremity function and were highly
satisfied with their physiotherapy treatment.
PMID- 27504035
TI - Using Outcome Measures in Daily Practice: Development and Evaluation of an
Implementation Strategy for Physiotherapists in the Netherlands.
AB - PURPOSE: To describe the development of an educational programme for
physiotherapists in the Netherlands, two toolkits of measurement instruments, and
the evaluation of an implementation strategy. METHOD: The study used a controlled
pre- and post-measurement design. A tailored educational programme for the use of
outcome measures was developed that consisted of four training sessions and two
toolkits of measurement instruments. Of 366 invited physiotherapists, 265
followed the educational programme (response rate 72.4%), and 235 randomly chosen
control physiotherapists did not (28% response rate). The outcomes measured were
participants' general attitude toward measurement instruments, their ability to
choose measurement instruments, their use of measurement instruments, the
applicability of the educational programme, and the changes in physiotherapy
practice achieved as a result of the programme. RESULTS: Consistent (not
occasional) use of measurement instruments increased from 26% to 41% in the
intervention group; in the control group, use remained almost the same (45% vs
48%). Difficulty in choosing an appropriate measurement instrument decreased from
3.5 to 2.7 on a 5-point Likert-type scale. Finally, 91% of respondents found the
educational programme useful, and 82% reported that it changed their
physiotherapy practice. CONCLUSIONS: The educational programme and toolkits were
useful and had a positive effect on physiotherapists' ability to choose among
many possible outcome measures.
PMID- 27504036
TI - An Evidence-Based Case Study of Unilateral Shin Splints: Do Red Flags Function in
Paediatric Osteosarcoma?
AB - Physiotherapists use red flags to screen for serious pathology. Paediatric
osteosarcoma is a rare disease, occurring predominantly in the area of the knee
and shoulder, and it is not always included by physiotherapists on a differential
diagnosis list. Traditional red flags do not always correspond to the initial
signs and symptoms of osteosarcoma. Physiotherapists should routinely palpate
along the length of the bone to detect a potential mass. The detection of a mass
or symptoms that do not follow the expected course indicates the need for
reassessment and possibly referral for further investigation.
PMID- 27504037
TI - Characteristics of People with Hip or Knee Osteoarthritis Deemed Not Yet Ready
for Total Joint Arthroplasty at Triage.
AB - PURPOSE: To identify the characteristics of people with hip or knee
osteoarthritis (OA) attending a regional triage centre for an initial consult who
are deemed not yet ready for total joint arthroplasty (TJA). METHODS: Initial
consultation notes (n=482) were reviewed retrospectively. Predictive variables
were derived from the literature a priori, and 14 of these variables were
suitable for inclusion in stepwise multiple logistic regression analyses.
RESULTS: Of the 222 eligible people, 131 (59%) were deemed not yet ready for TJA.
Five variables entered into the model ([Formula: see text]=133.19, p<0.001) for
an overall success rate of 81.1%. Those deemed not yet ready for TJA were more
likely to have knee OA (vs. hip OA; odds ratio [OR]=0.352, p=0.018), to have less
severe OA (OR=0.246 for each category increase in severity, p<0.001), to use no
gait aid (vs. cane; OR=0.390, p=0.033), and to have a higher Lower Extremity
Functional Scale score (OR=1.050 for each 1-point increase, p=0.003) and better
joint status as measured by the Knee Society Scale or Hip Harris Scale (OR=3.946
for each category increase, p=0.007). CONCLUSION: Considering these
characteristics will help clinicians to identify individuals likely to require
interventions other than TJA.
PMID- 27504038
TI - Standardized Patients versus Volunteer Patients for Physical Therapy Students'
Interviewing Practice: A Pilot Study.
AB - PURPOSE: To compare the use of standardized patients (SPs) and volunteer patients
(VPs) for physical therapy students' interviewing practice in terms of students'
perception and overall costs. METHODS: Students in the Master of Physical Therapy
programme (n=80) at a Canadian university were divided into 20 groups of 4 and
were randomly assigned to interview either an SP (10 groups) or a VP (10 groups).
Students completed a survey about their perception of the usefulness of the
activity and the ease and depth of information extraction. Survey responses as
well as costs of the interview exercise were compared between SP and VP groups.
RESULTS: No statistically significant between-groups difference was found for the
majority of survey items. The cost of using an SP was $148, versus $50 for a VP.
CONCLUSIONS: Students' perceptions of the usefulness of the activity in helping
them to develop their interview skills and of the ease and depth of extracting
information were similar for both SPs and VPs. Because the cost of using an SP is
about three times that of using a VP, using VPs seem to be a more cost-effective
option.
PMID- 27504039
TI - Enhanced Patient-Centred Care: Physiotherapists' Perspectives on the Impact of
International Clinical Internships on Canadian Practice.
AB - PURPOSE: To explore the perspectives of physiotherapists who participated in an
international clinical internship (ICI) in low- or middle-income countries
(LMICs) during their physiotherapy (PT) training in a Canadian PT programme
regarding the ICI's impact on their PT practice in Canada. METHODS: This
qualitative descriptive study used in-depth semi-structured interviews. Data were
organized using NVivo; inductive and deductive coding were used to analyze data
and develop broader themes. RESULTS: The 13 practising Canadian physiotherapists
interviewed described three enhanced capacities: (1) critical reflection on
culture, values and practice; (2) communication skills; and (3) creativity and
resourcefulness. These capacities were perceived to transfer to Canadian practice
by enhancing participants' ability to deliver patient-centred care, specifically
through an enhanced understanding of patients' values and social determinants of
health, regardless of the Canadian setting or patient population. CONCLUSIONS:
For PT students considering an ICI, the study findings provide insight into the
perceived impact of ICIs on Canadian practice. For PT academic programmes, the
findings can guide decisions on the extent of investment in ICIs as learning
opportunities that will enhance practice in Canada.
PMID- 27504040
TI - What Does the Cochrane Collaboration Say about the Effectiveness of Chest
Physiotherapy in Respiratory Conditions?
PMID- 27504041
TI - Cultural Humility: A Way of Thinking to Inform Practice Globally.
PMID- 27504042
TI - Current Uses (and Potential Misuses) of Facebook: An Online Survey in
Physiotherapy.
AB - PURPOSE: In recent years, the use of social media such as Facebook has become
extremely popular and widespread in our society. Among users are health care
professionals, who must develop ways to extend their professionalism online.
Before issuing formal guidelines, policies, or recommendations to guide online
behaviours, there is a need to know to what extent Facebook influences the
professional life of physiotherapy professionals. Our goal was to explore
knowledge and behaviour that physiotherapists and physical rehabilitation
therapists practicing in Quebec have of Facebook. METHOD: We used an empirical
cross-sectional online survey design (n=322, response rate 4.5%). RESULTS: The
results showed that 84.3% of physiotherapy professionals had a Facebook account.
Almost all had colleagues or former colleagues as Facebook friends, 21% had
patients as friends, and 27% had employers as friends. More than a third of
workplaces had clinic pages with information intended for the public. Regarding
workplace Facebook policies, 37.3% said that there was no policy and another
41.6% were not aware whether there was one or not. CONCLUSION: There appears to
be a need to establish guidelines regarding the use of social media for
physiotherapy professionals to ensure maintenance of professionalism and ethical
conduct.
PMID- 27504043
TI - Validity of the Handheld Dynamometer Compared with an Isokinetic Dynamometer in
Measuring Peak Hip Extension Strength.
AB - PURPOSE: To determine whether the handheld dynamometer (HHD) is an appropriate
tool to assess and quantify peak hip extension strength in prone standing
position by (1) evaluating the concurrent validity of the HHD versus an
isokinetic dynamometer (IKD), (2) establishing the minimal detectable change
(MDC), and (3) determining the validity of single-trial versus multi-trial
measures. METHOD: A convenience sample of 20 healthy adults was recruited for
this cross-sectional study. Measures of peak hip extension strength were
collected in prone standing position with both the HHD and the IKD and in supine
position with the IKD. RESULTS: Values of r were 0.37 for HHD versus IKD prone
standing and 0.51 for HHD versus IKD supine. MDC was 14.8 Nm for the HHD, 25.6 Nm
for IKD prone standing, and 41.5 Nm for IKD supine. High correlations (r values
of 0.92-0.94) were observed between trial 1 and the mean of three trials.
CONCLUSIONS: The HHD has moderate concurrent validity in measuring peak hip
extension strength in the prone standing position in healthy adults. MDC for hip
extension strength was lowest using the HHD. Single-trial values showed a high
correlation with three-trial mean values.
PMID- 27504044
TI - Shoulder Retractor Strengthening Exercise to Minimize Rhomboid Muscle Activity
and Subacromial Impingement.
AB - PURPOSE: We investigated the best position for shoulder retractor strengthening
exercise to maximize middle trapezius activity and minimize rhomboid major
activity. Although both trapezius and rhomboids are scapular retractors,
rhomboids also act as downward rotators of the scapula, which can worsen
subacromial impingement. METHODS: Twelve healthy participants (age 30 [SD 6] y)
with no history of shoulder pain were recruited for this study, which used fine
wire electromyography to examine maximal muscle activation of the middle
trapezius and rhomboid major muscle fibres in four different positions: with the
shoulder in 90 degrees abduction with elbow completely extended and (1) shoulder
internal rotation, (2) shoulder neutral rotation, (3) shoulder external rotation,
and (4) rowing (shoulder neutral rotation and elbow flexed 90 degrees ). The
ratio of trapezius to rhomboid muscles was compared with Wilcoxon signed-rank
tests. RESULTS: Muscle activation ratio during shoulder retraction exercise was
significantly lower by 22% (i.e., rhomboid was more active than middle trapezius)
when performed with the shoulder in rowing position (elbow flexed) than with the
shoulder in external rotation (elbow extended) position (p=0.031). All four
positions produced coactivation of trapezius and rhomboids. DISCUSSION: Rowing
position may not be the best position for shoulder retractor strengthening in
patients with impingement syndrome. The preferable position for maximizing middle
trapezius activity and minimizing rhomboid activity may be shoulder external
rotation with elbow extended.
PMID- 27504045
TI - A Roland Morris Disability Questionnaire Target Value to Distinguish between
Functional and Dysfunctional States in People with Low Back Pain.
AB - PURPOSE: To estimate a threshold Roland Morris Disability Questionnaire (RMQ)
value that could be used to classify patients with low back pain (LBP) as
functional or dysfunctional. METHODS: In this secondary analysis of data from a
study that estimated clinically important RMQ change scores, participants were
adults with LBP attending one of three physical therapy clinics. Diagnostic test
methodology and a reference standard of goals met were applied to estimate a
threshold RMQ value that best distinguished between participants with a
functional status and those whose status was dysfunctional. RESULTS: Of 143
participants, 104 (73%) met their goals. An RMQ threshold value of 4/24 best
distinguished between those who met their goals and those who did not.
Sensitivity and specificity for a threshold score of 4 were 94% (95% CI, 88-98)
and 69% (95% CI, 52-83), respectively. CONCLUSIONS: A threshold value of 4 RMQ
points provided a reasonably accurate classification of patients. Further
research is necessary to cross-validate this estimate and to examine the
stability of the estimated value in people with diverse functional demands.
PMID- 27504046
TI - Promoting Physical Activity and Exercise in Daily Practice: Current Practices,
Barriers, and Training Needs of Physiotherapists in Eastern Nigeria.
AB - PURPOSE: To investigate current practices, barriers, and training needs for the
promotion of physical activity (PA) in physiotherapy practices in eastern
Nigeria. METHODS: A total of 141 fully licensed physiotherapists in southeast
Nigeria were invited to participate in a cross-sectional survey consisting of 23
questions in five key sections, focusing mainly on risk-factor management
practices of physiotherapists. RESULTS: A total of 103 questionnaires were
returned. Respondents ranged in age from 25 to 54 years and reported a mean of 11
(SD 10) years of clinical experience. Respondents reported that they regularly
assess and advise their clients on PA but rarely give written prescriptions.
Although they are confident in assessing and advising their clients on PA and
consider including PA intervention as a priority in daily practice, lack of time
and lack of access to materials were reported as barriers to effective PA
intervention. CONCLUSION: Findings showed the potential for physiotherapists to
address physical inactivity and highlighted several barriers. Strategies are
needed to improve contact time with clients and make material promoting PA
available to practising physiotherapists.
PMID- 27504047
TI - Correlation between Limb Muscle Endurance, Strength, and Functional Capacity in
People with Chronic Obstructive Pulmonary Disease.
AB - PURPOSE: To examine the correlation between limb muscle function (endurance and
strength) and functional capacity in upper limbs (ULs) and lower limbs (LLs) of
people with chronic obstructive pulmonary disease (COPD). METHOD: This article
describes a secondary analysis of data from a randomized controlled trial. A
stationary dynamometer was used to measure isokinetic muscle strength and
endurance; the 6-minute walk test, the 6-minute pegboard and ring test, and the
unsupported UL exercise test were used to measure functional capacity. RESULTS:
Participants were 44 adults with COPD. Muscle strength and endurance in ULs and
LLs demonstrated a moderate to strong correlation with functional capacity. When
controlling for muscle strength, muscle endurance was moderately correlated with
functional capacity in ULs and LLs, but when controlling for muscle endurance,
there was no positive and significant correlation between muscle strength and
functional capacity for the ULs or LLs. CONCLUSIONS: Functional capacity seems to
be more closely related to limb muscle endurance than to limb muscle strength in
people with COPD.
PMID- 27504048
TI - Leadership in Physical Therapy: Characteristics of Academics and Managers: A
Brief Report.
AB - PURPOSE: To explore the characteristics of physical therapy leaders in academic
and managerial roles. METHODS: This quantitative, cross-sectional study used an
online questionnaire administered via email to Canadian physical therapists
recruited through the Canadian Physiotherapy Association and via additional
emails targeted to academic and health care institutions. Individuals who met the
inclusion criteria after completion of the questionnaire were asked to complete
the Clifton StrengthsFinder, which was used to objectively assess the extent to
which participants exhibited personality characteristics. We calculated
frequencies for demographic characteristics and the 10 most prominent
characteristics for participants in academic and managerial roles. RESULTS: A
total of 88 participants completed the questionnaire (52 managers, 36 academics).
The most prevalent strengths among both academics and managers were the learner
and achiever characteristics. CONCLUSIONS: Academics and managers in physical
therapy share similar core characteristics, with slight variations in secondary
characteristics.
PMID- 27504049
TI - Mechanical Low Back Pain: Secular Trend and Intervention Topics of Randomized
Controlled Trials.
AB - PURPOSE: To evaluate the number of published randomized controlled trials (RCTs)
focusing on mechanical low back pain (MLBP) rehabilitation, the secular (i.e.,
long-term) trend, and the distribution of interventions studied. METHODS: All
included RCTs were extracted from all Cochrane systematic reviews focusing on
rehabilitation therapies for MLBP, and two independent reviewers screened and
analyzed the information on interventions. RESULTS: After removal of duplicates,
the data set consisted of 196 RCTs published between 1961 and 2010. The number of
RCTs published increased consistently over time: 2 trials (1% of the total) were
published in 1961-1970, 10 (5%) in 1971-1980, 41 (21%) in 1981-1990, 68 (35%) in
1991-2000, and 75 (38%) in 2001-2010. The intervention of interest in the
majority of RCTs was exercise therapy (115/399; 29%), followed by spinal
manipulation therapies (60/399; 15%). CONCLUSION: The number of RCTs focusing on
MLBP has risen over time; of all interventions studied, exercise therapy has
attracted the most research interest.
PMID- 27504050
TI - Canadian Physiotherapy Assessment of Clinical Performance: Face and Content
Validity.
AB - PURPOSE: To investigate face and content validity of a draft measure to be used
across Canada to assess physiotherapy students' performance in clinical
education, through broad consultation with physiotherapy clinical instructors
(CIs) across Canada. METHODS: An online survey was used to collect input on the
draft measure. In addition to demographics, the questionnaire included questions
on the preferred rating scale, the items within the measure that should have
their own rating scale, and general impressions. RESULTS: Among the 259 CIs who
completed the survey, a discrete rating scale with six anchors and 10 boxes or a
continuous-line rating scale with six anchors was preferred. Respondents favoured
using one rating scale for each key competency in the Expert role but considered
a single rating scale sufficient for assessing the Scholarly Practitioner role.
CIs agreed that the proposed measure would allow them to assess a student who was
performing poorly or very well. The name Canadian Physiotherapy Assessment of
Clinical Performance (ACP) received the most votes in the questionnaire.
CONCLUSIONS: CIs' collective preferences on the design, organization, and naming
of the measure they will use in evaluating students are reflected in the second
draft of the ACP.
PMID- 27504051
TI - Diminishing Effect Sizes with Repeated Exposure to Evidence-Based Practice
Training in Entry-Level Health Professional Students: A Longitudinal Study.
AB - PURPOSE: To investigate the magnitude of change in outcomes after repeated
exposure to evidence-based practice (EBP) training in entry-level health
professional students. METHOD: Using an observational cross-sectional analytic
design, the study tracked 78 students in physiotherapy, podiatry, health science,
medical radiations, and human movement before and after two sequential EBP
courses. The first EBP course was aimed at developing foundational knowledge of
and skills in the five steps of EBP; the second was designed to teach students to
apply these steps. Two EBP instruments were used to collect objective (actual
knowledge) and self-reported (terminology, confidence, practice, relevance,
sympathy) data. Participants completed both instruments before and after each
course. RESULTS: Effect sizes were larger after the first course than after the
second for relevance (0.72 and 0.26, respectively), practice (1.23 and 0.43),
terminology (2.73 and 0.84), and actual knowledge (1.92 and 1.45); effect sizes
were larger after the second course for sympathy (0.03 and 0.14) and confidence
(0.81 and 1.12). CONCLUSIONS: Knowledge and relevance changed most meaningfully
(i.e., showed the largest effect size) for participants with minimal prior
exposure to training. Changes in participants' confidence and attitudes may
require a longer time frame and repeated training exposure.
PMID- 27504052
TI - Boys, Transitions, and Physical (In)activity: Exploring the Socio-Behavioural
Mediators of Participation.
AB - PURPOSE: To explore the socio-behavioural mechanisms that motivate or dissuade
boys' participation in physical activity (PA) as they transition into adolescence
and their implications for physical therapy. METHODS: This critical qualitative
study involved in-depth interviews using active interviewing techniques with 15
adolescent boys. Data generation and analysis were driven by techniques of
grounded theory and Bourdieu's sociology of practice. RESULTS: The analysis
identified intersectional relationships among emotions, the inherent pleasures of
movement, and a sense of connectedness to PA, each of which acted as a mediating
mechanism in motivating participation in PA. Analogously, body dissatisfaction,
negative self-perceptions, and repeated instances of explicit and symbolic
bullying intersected to dissuade boys from participating and created apathy
toward PA. CONCLUSION: Identifying socio-behavioural mechanisms that motivate or
dissuade physically active behaviour contributes new knowledge toward
understanding PA attrition among boys transitioning to adolescence. As health
advocates and movement experts, physiotherapists have an important role in
helping adolescents of all abilities to participate in activities that provide
them with meaning, inclusivity, and a sense of connectedness to PA.
PMID- 27504053
TI - What Does the Cochrane Collaboration Say about Interventions to Promote Physical
Activity?
PMID- 27504054
TI - The Efficacy and Safety of Antipsychotic Medications in the Treatment of
Psychosis in Patients with Parkinson's Disease.
AB - Psychotic symptoms are present in up to 50% of patients with Parkinson's disease.
These symptoms have detrimental effects on patients' and caregivers' quality of
life and may predict mortality. The pathogenesis of psychotic symptoms in
Parkinson's disease is complex, but the use of dopaminergic medications is one of
the risk factors. The treatment of psychotic symptoms in Parkinson's disease is
complicated due to the ability of antipsychotic medications to worsen motor
symptoms. The efficacy of clozapine in the treatment of psychosis in patients
with Parkinson's disease has been confirmed in several clinical trials; however,
the adverse effects and the necessity of blood count monitoring are the reasons
why the use of this drug is challenging. The studies on safety and efficacy of
other antipsychotics conflicting results. The use of antipsychotics in these
patients is also associated with increased mortality. Psychotic symptoms in
Parkinson's disease per se are also proven predictors of mortality. Thus it is
necessary to treat psychotic symptoms but the choice of an antipsychotic should
be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic
option with more favorable adverse effects profile is now available for this
indication, but careful postmarketing monitoring is necessary to establish the
true picture of this drug's long-term safety and efficacy.
PMID- 27504055
TI - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-glucoside Isolated from Polygoni
Multiflori Ameliorates the Development of Periodontitis.
AB - Periodontitis, a chronic infection by periodontopathic bacteria, induces
uncontrolled inflammation, which leads to periodontal tissue destruction.
2,3,5,4'-Tetrahydroxystilbene-2-O-beta-glucoside (THSG), a polyphenol extracted
from Polygoni Multiflori, reportedly has anti-inflammatory properties. In this
study, we investigated the mechanisms of THSG on the Porphyromonas gingivalis
induced inflammatory responses in human gingival fibroblasts and animal modeling
of ligature-induced periodontitis. Human gingival fibroblast cells were treated
with lipopolysaccharide (LPS) extracted from P. gingivalis in the presence of
resveratrol or THSG to analyze the expression of TNF-alpha, IL-1beta, and IL-6
genes. Increased AMP-activated protein kinase (AMPK) activation and SirT1
expression were induced by THSG. Treatment of THSG decreased the expression of
LPS-induced inflammatory cytokines, enhanced AMPK activation, and increased the
expression of SirT1. In addition, it suppressed the activation of NF-kappaB when
cells were stimulated with P. gingivalis LPS. The anti-inflammatory effect of
THSG and P. Multiflori crude extracts was reproduced in ligature-induced
periodontitis animal modeling. In conclusion, THSG inhibited the inflammatory
responses of P. gingivalis-stimulated human gingival fibroblasts and ameliorated
ligature-induced periodontitis in animal model.
PMID- 27504056
TI - A radiographic simulation study of fixed superior pubic ramus fractures with
retrograde screw insertion.
AB - OBJECTIVES: The study's aim is to calculate the parameters for retrograde
insertion points for fixed superior pubic ramus fractures. METHODS: From the
pubic symphysis, diameter and length of the screw were measured, as well as the
angle between the screw axis and the 3 planes. RESULTS: When the diameter was
fixed at 4.5 mm, the maximum lengths were 125 mm and 119 mm. CONCLUSIONS: When
the fracture occurs in Zone I, the penetration point could be selected in the
pubic symphysis pubis angle to ensure that medial fracture fragments have
sufficient screw channel length.
PMID- 27504057
TI - Radiographic and functional evaluation of low profile dorsal versus volar plating
for distal radius fractures.
AB - INTRODUCTION: Fracture of the distal radius is a common clinical problem. Complex
fracture requires open reduction and stabilization with plating to restore
anatomy. Dorsal plating has advantages of buttressing the fracture better but
often complicated with tendon problems as per literature. The rate of
complications however, was not compared between the low-profile dorsal and the
volar plates. METHODOLOGY: This was a retrospective study on seventy one patients
with dorsally angulated or displaced distal radius fractures, who underwent
fixation of fractures with either dorsal or volar locking plate from Jan - Nov
2012. Preoperative radiographs were classified based on Universal and Fernandez
classification. Postoperative radiographs were assessed for anatomical
restoration of Radial length, radial inclination and volar tilt. Tendon and nerve
related complications were assessed and functional evaluation was performed on
the basis of PRWE (Patient related wrist evaluation) score. RESULTS: Both groups
were matched for their demographic profile and fracture types (p 0.033). Dorsal
plating group had 89% excellent/good restoration and fair in 11%. Volar group had
96% excellent/good restoration and fair in 4%. Statistical analysis was performed
with unpaired t test for radiographic parameters. Three patients had tendon
related complications in dorsal plating group; two patients in volar group had
nerve related complications. Functional outcome with PRWE was comparable between
two groups. CONCLUSION: Results with low profile dorsal plating were comparable
to volar plating. Therefore dorsal plating can be used as an alternative method
when dorsal buttressing of comminuted fracture is required, especially with
concomitant osteoporosis.
PMID- 27504058
TI - The epidemiology of thoracolumbar trauma: A meta-analysis.
AB - PURPOSE: To describe the epidemiology of thoracolumbar fractures and associated
injuries in blunt trauma patients. METHODS: A systematic review and metaanalysis
was performed based on a MEDLINE database search using MeSH terms for studies
matching our inclusion criteria. The search yielded 21 full-length articles, each
sub-grouped according to content. Data extraction and multiple analyses were
performed on descriptive data. RESULTS: The rate of thoracolumbar fracture in
blunt trauma patients was 6.90% (+/-3.77, 95% CI). The rate of spinal cord injury
was 26.56% (+/-10.70), and non-contiguous cervical spine fracture occurred in
10.49% (+/-4.17). Associated injury was as follows: abdominal trauma 7.63% (+/
9.74), thoracic trauma 22.64% (+/-13.94), pelvic trauma 9.39% (+/-6.45),
extremity trauma 18.26% (+/-5.95), and head trauma 12.96% (+/-2.01). Studies that
included cervical spine fracture with thoracolumbar fracture had the following
rates of associated trauma: 3.78% (+/-5.94) abdominal trauma, 21.65% (+/-16.79)
thoracic trauma, 3.62% (+/-1.07) pelvic trauma, 18.36% (+/-4.94) extremity
trauma, and 15.45% (+/-11.70) head trauma. A subgroup of flexion distraction
injuries showed an associated intra-abdominal injury rate of 38.70% (+/-13.30).
The most common vertebra injured was L1 at a rate of 34.40% (+/-15.90). T7 was
the most common non-junctional vertebra injured at 3.90% (+/-1.09). Burst/AO type
A3 fractures were the most common morphology 39.50% (+/-16.30) followed by 33.60%
(+/-15.10) compression/AO type A1, 14.20% (+/-8.08) fracture dislocation/AO type
C, and 6.96% (+/-3.50) flexion distraction/AO type B. The most common etiology
for a thoracolumbar fracture was motor vehicle collision 36.70% (+/-5.35),
followed by high-energy fall 31.70% (+/-6.70). CONCLUSIONS: Here we report the
incidence of thoracolumbar fracture in blunt trauma and the spectrum of
associated injuries. To our knowledge, this paper provides the first
epidemiological road map for blunt trauma thoracolumbar injuries.
PMID- 27504059
TI - Total hip arthroplasty in patients with haemophilia - What are the risks of
bleeding in the immediate peri-operative period?
AB - BACKGROUND: Undergoing a major surgical intervention such as total hip
arthroplasty (THA) with an underlying clotting disorder like haemophilia poses
its own unique challenges. Despite the advances in factor replacement and medical
management, the potential for excessive and uncontrolled haemorrhage still
exists. The aim of this study was to quantify blood loss, peri-operative
transfusion requirements and risk of haematoma formation in a cohort of patients
with haemophilia undergoing THA. METHODS: All patients with haemophilia types A
or B who had undergone THA in the previous 10 years were identified from the
Hospital In-Patient Enquiry system and theatre logs. A comprehensive review of
operative records, laboratory parameters and peri-operative haematological
management was conducted. RESULTS: Eleven male patients (12 THA) were identified.
The mean age was 56 years (range 28-76). The mean intra-operative blood loss was
502 ml (100-1250 ml) compared to an established normal blood loss of 400 ml. The
mean drop in haemoglobin was 3.25 g/dl in 48 h. Only one patient required a post
operative transfusion of two units of red cell concentrate. There were no
complications of haematoma formation. CONCLUSION: The results in our institution
compare favourably with the established blood loss reported in the literature and
by assessment with International Guidelines. Average blood loss in patients with
haemophilia was higher than the established normal, but there was no increased
transfusion requirement.
PMID- 27504060
TI - Death and Neurological Devastation From Intrathecal Vinca Alkaloids.
AB - Inadvertent intrathecal vincristine administration causes fatalities.
PMID- 27504062
TI - Drug and Device News.
AB - Approvals, new indications, regulatory activities, and more.
PMID- 27504061
TI - Compounding Pharmacists Unhappy With New FDA Guidance Documents : Rules Severely
Limit Distribution.
AB - Recent FDA compounding guidances raise hackles.
PMID- 27504063
TI - Pharmaceutical Approval Update.
AB - Venetoclax (Venclexta) for chronic lymphocytic leukemia; riboflavin 5'-phosphate
solutions (Photrexa Viscous and Photrexa) for progressive keratoconus; and
pimavanserin (Nuplazid) for Parkinson's disease psychosis.
PMID- 27504064
TI - Ceftazidime-Avibactam (Avycaz): For the Treatment of Complicated Intra-Abdominal
and Urinary Tract Infections.
AB - Ceftazidime-avibactam (Avycaz) for the treatment of complicated infections.
PMID- 27504065
TI - Congress and Federal Agencies Address Opioid Abuse Epidemic, But Will New
Initiatives Be Successful?
AB - In response to the alarming rate of opioid overdose deaths in the U.S., the
President, Congress, and federal agencies are making efforts to reduce the number
of fatalities.
PMID- 27504066
TI - Immunization in the United States: Recommendations, Barriers, and Measures to
Improve Compliance: Part 2: Adult Vaccinations.
AB - Despite annual recommendations, American adults remain inadequately vaccinated.
The author outlines how compliance may be improved through health care
professional interventions, as well as government and community-based programs.
PMID- 27504067
TI - An Annual Formulary Review Strategy Implemented by a Saudi Health System.
AB - As in the U.S., there is no unified national formulary in Saudi Arabia, so
individual institutions must develop their own medication lists. A Saudi health
system's strategy for maintaining formulary safety, efficacy, and cost
effectiveness is described.
PMID- 27504068
TI - European League Against Rheumatism And American Diabetes Association.
AB - We present EULAR sessions on the latest treatments for rheumatic disease with an
infliximab biosimilar, certolizumab pegol, secukinumab, and bimekizumab. We also
report on significant developments in diabetes presented at ADA's Scientific
Sessions.
PMID- 27504069
TI - Launch of Breakthrough Therapies Will Reshape Renal Cell Carcinoma Market.
AB - Tyrosine kinase inhibitors (TKIs) are leading systemic therapies for the
treatment of renal cell carcinoma. However, programmed death-1 inhibitors,
promising new agents in development, may surpass TKIs as the standard of care in
the future.
PMID- 27504070
TI - Research Briefs.
PMID- 27504072
TI - Microstructure and Mechanical Properties of Microwave Sintered ZrO2 Bioceramics
with TiO2 Addition.
AB - The microwave sintered zirconia ceramics with 0, 1, 3, and 5 wt% TiO2 addition at
a low sintering temperature of 1300 degrees C and a short holding time of 1 hour
were investigated. Effect of contents of TiO2 addition on microstructure and
mechanical properties of microwave sintered zirconia bioceramics was reported. In
the sintered samples, the main phase is monoclinic zirconia (m-ZrO2) phase and
minor phase is tetragonal zirconia (t-ZrO2) phase. The grain sizes increased with
increasing the TiO2 contents under the sintering temperature of 1300 degrees C.
Although the TiO2 phase was not detected in the XRD pattern, Ti and O elements
were detected in the EDS analysis. The presence of TiO2 effectively improved
grain growth of the ZrO2 ceramics. The Vickers hardness was in the range of 125
to 300 Hv and increased with the increase of TiO2 contents. Sintering temperature
dependence on the Vickers hardness was also investigated from 1150 degrees C to
1300 degrees C, showing the increase of Vickers hardness with the increase of the
sintering temperature as well as TiO2 addition.
PMID- 27504071
TI - Management of HIV Infection during Pregnancy in the United States: Updated
Evidence-Based Recommendations and Future Potential Practices.
AB - All HIV-infected women contemplating pregnancy should initiate combination
antiretroviral therapy (cART), with a goal to achieve a maternal serum HIV RNA
viral load beneath the laboratory level of detection prior to conceiving, as well
as throughout their pregnancy. Successfully identifying HIV infection during
pregnancy through screening tests is essential in order to prevent in utero and
intrapartum transmission of HIV. Perinatal HIV transmission can be less than 1%
when effective cART, associated with virologic suppression of HIV, is given
during the ante-, intra-, and postpartum periods. Perinatal HIV guidelines,
developed by organizations such as the World Health Organization, American
College of Obstetricians and Gynecologists, and the US Department of Health and
Human Services, are constantly evolving, and hence the aim of our review is to
provide a useful concise review for medical providers caring for HIV-infected
pregnant women, summarizing the latest and current recommendations in the United
States.
PMID- 27504073
TI - When Does Feature Search Fail to Protect Against Attentional Capture?
AB - When participants search for a shape (e.g., a circle) among a set of homogenous
shapes (e.g., triangles) they are subject to distraction by color singletons that
are more salient than the target. However, when participants search for a shape
among heterogeneous shapes, the presence of a non-target color singleton does not
slow responses to the target. Attempts have been made to explain these results
from both bottom-up and top-down perspectives. What both accounts have in common
is that they do not predict the occurrence of attentional capture on typical
feature search displays. Here, we present a case where manipulating selection
history, rather than the displays themselves, leads to attentional capture on
feature search trials. The ability to map specific colors to the target and
distractor appears to be what enables resistance to capture during feature
search.
PMID- 27504074
TI - Measurement and modeling of polarized specular neutron reflectivity in large
magnetic fields.
AB - The presence of a large applied magnetic field removes the degeneracy of the
vacuum energy states for spin-up and spin-down neutrons. For polarized neutron
reflectometry, this must be included in the reference potential energy of the
Schrodinger equation that is used to calculate the expected scattering from a
magnetic layered structure. For samples with magnetization that is purely
parallel or antiparallel to the applied field which defines the quantization
axis, there is no mixing of the spin states (no spin-flip scattering) and so this
additional potential is constant throughout the scattering region. When there is
non-collinear magnetization in the sample, however, there will be significant
scattering from one spin state into the other, and the reference potentials will
differ between the incoming and outgoing wavefunctions, changing the angle and
intensities of the scattering. The theory of the scattering and recommended
experimental practices for this type of measurement are presented, as well as an
example measurement.
PMID- 27504075
TI - Investigation of dissimilar metal welds by energy-resolved neutron imaging.
AB - A nondestructive study of the internal structure and compositional gradient of
dissimilar metal-alloy welds through energy-resolved neutron imaging is described
in this paper. The ability of neutrons to penetrate thick metal objects (up to
several cm) provides a unique possibility to examine samples which are opaque to
other conventional techniques. The presence of Bragg edges in the measured
neutron transmission spectra can be used to characterize the internal residual
strain within the samples and some microstructural features, e.g. texture within
the grains, while neutron resonance absorption provides the possibility to map
the degree of uniformity in mixing of the participating alloys and intermetallic
formation within the welds. In addition, voids and other defects can be revealed
by the variation of neutron attenuation across the samples. This paper
demonstrates the potential of neutron energy-resolved imaging to measure all
these characteristics simultaneously in a single experiment with sub-mm spatial
resolution. Two dissimilar alloy welds are used in this study: Al autogenously
laser welded to steel, and Ti gas metal arc welded (GMAW) to stainless steel
using Cu as a filler alloy. The cold metal transfer variant of the GMAW process
was used in joining the Ti to the stainless steel in order to minimize the heat
input. The distributions of the lattice parameter and texture variation in these
welds as well as the presence of voids and defects in the melt region are mapped
across the welds. The depth of the thermal front in the Al-steel weld is clearly
resolved and could be used to optimize the welding process. A highly textured
structure is revealed in the Ti to stainless steel joint where copper was used as
a filler wire. The limited diffusion of Ti into the weld region is also verified
by the resonance absorption.
PMID- 27504076
TI - Rotation of X-ray polarization in the glitches of a silicon crystal
monochromator.
AB - EXAFS studies on dilute samples are usually carried out by collecting the
fluorescence yield using a large-area multi-element detector. This method is
susceptible to the 'glitches' produced by all single-crystal monochromators.
Glitches are sharp dips or spikes in the diffracted intensity at specific crystal
orientations. If incorrectly compensated, they degrade the spectroscopic data.
Normalization of the fluorescence signal by the incident flux alone is sometimes
insufficient to compensate for the glitches. Measurements performed at the state
of-the-art wiggler beamline I20-scanning at Diamond Light Source have shown that
the glitches alter the spatial distribution of the sample's quasi-elastic X-ray
scattering. Because glitches result from additional Bragg reflections, multiple
beam dynamical diffraction theory is necessary to understand their effects. Here,
the glitches of the Si(111) four-bounce monochromator of I20-scanning just above
the Ni K edge are associated with their Bragg reflections. A fitting procedure
that treats coherent and Compton scattering is developed and applied to a sample
of an extremely dilute (100 micromolal) aqueous solution of Ni(NO3)2. The
depolarization of the wiggler X-ray beam out of the electron orbit is modeled.
The fits achieve good agreement with the sample's quasi-elastic scattering with
just a few parameters. The X-ray polarization is rotated up to +/-4.3 degrees
within the glitches, as predicted by dynamical diffraction. These results will
help users normalize EXAFS data at glitches.
PMID- 27504077
TI - Interfibrillar packing of bovine cornea by table-top and synchrotron scanning
SAXS microscopy.
AB - Bovine cornea was studied with scanning small-angle X-ray scattering (SAXS)
microscopy, by using both synchrotron radiation and a microfocus laboratory
source. A combination of statistical (adaptive binning and canonical correlation
analysis) and crystallographic (pair distribution function analysis) approaches
allowed inspection of the collagen lateral packing of the supramolecular
structure. Results reveal (i) a decrease of the interfibrillar distance and of
the shell thickness around the fibrils from the periphery to the center of the
cornea, (ii) a uniform fibril diameter across the explored area, and (iii) a
distorted quasi-hexagonal arrangement of the collagen fibrils. The results are in
agreement with existing literature. The overlap between laboratory and
synchrotron-radiation data opens new perspectives for further studies on collagen
based/engineered tissues by the SAXS microscopy technique at laboratory-scale
facilities.
PMID- 27504078
TI - Dragonfly: an implementation of the expand-maximize-compress algorithm for single
particle imaging.
AB - Single-particle imaging (SPI) with X-ray free-electron lasers has the potential
to change fundamentally how biomacromolecules are imaged. The structure would be
derived from millions of diffraction patterns, each from a different copy of the
macromolecule before it is torn apart by radiation damage. The challenges posed
by the resultant data stream are staggering: millions of incomplete, noisy and un
oriented patterns have to be computationally assembled into a three-dimensional
intensity map and then phase reconstructed. In this paper, the Dragonfly software
package is described, based on a parallel implementation of the expand-maximize
compress reconstruction algorithm that is well suited for this task. Auxiliary
modules to simulate SPI data streams are also included to assess the feasibility
of proposed SPI experiments at the Linac Coherent Light Source, Stanford,
California, USA.
PMID- 27504079
TI - CFEL-ASG Software Suite (CASS): usage for free-electron laser experiments with
biological focus.
AB - CASS [Foucar et al. (2012). Comput. Phys. Commun.183, 2207-2213] is a well
established software suite for experiments performed at any sort of light source.
It is based on a modular design and can easily be adapted for use at free
electron laser (FEL) experiments that have a biological focus. This article will
list all the additional functionality and enhancements of CASS for use with FEL
experiments that have been introduced since the first publication. The article
will also highlight some advanced experiments with biological aspects that have
been performed.
PMID- 27504080
TI - WavePropaGator: interactive framework for X-ray free-electron laser optics design
and simulations.
AB - This article describes the WavePropaGator (WPG) package, a new interactive
software framework for coherent and partially coherent X-ray wavefront
propagation simulations. The package has been developed at European XFEL for
users at the existing and emerging free-electron laser (FEL) facilities, as well
as at the third-generation synchrotron sources and future diffraction-limited
storage rings. The WPG addresses the needs of beamline scientists and user groups
to facilitate the design, optimization and improvement of X-ray optics to meet
their experimental requirements. The package uses the Synchrotron Radiation
Workshop (SRW) C/C++ library and its Python binding for numerical wavefront
propagation simulations. The framework runs reliably under Linux, Microsoft
Windows 7 and Apple Mac OS X and is distributed under an open-source license. The
available tools allow for varying source parameters and optics layouts and
visualizing the results interactively. The wavefront history structure can be
used for tracking changes in every particular wavefront during propagation. The
batch propagation mode enables processing of multiple wavefronts in workflow
mode. The paper presents a general description of the package and gives some
recent application examples, including modeling of full X-ray FEL beamlines and
start-to-end simulation of experiments.
PMID- 27504081
TI - Condor: a simulation tool for flash X-ray imaging.
AB - Flash X-ray imaging has the potential to determine structures down to molecular
resolution without the need for crystallization. The ability to accurately
predict the diffraction signal and to identify the optimal experimental
configuration within the limits of the instrument is important for successful
data collection. This article introduces Condor, an open-source simulation tool
to predict X-ray far-field scattering amplitudes of isolated particles for
customized experimental designs and samples, which the user defines by an atomic
or a refractive index model. The software enables researchers to test whether
their envisaged imaging experiment is feasible, and to optimize critical
parameters for reaching the best possible result. It also aims to support
researchers who intend to create or advance reconstruction algorithms by
simulating realistic test data. Condor is designed to be easy to use and can be
either installed as a Python package or used from its web interface
(http://lmb.icm.uu.se/condor). X-ray free-electron lasers have high running costs
and beam time at these facilities is precious. Data quality can be substantially
improved by using simulations to guide the experimental design and simplify data
analysis.
PMID- 27504082
TI - Hyperbilirubinemia without Transaminitis during Combined Therapy with Daclatasvir
and Asunaprevir.
AB - Daclatasvir (DCV) and asunaprevir (ASV) are direct-acting antivirals (DAAs) used
in the treatment of chronic hepatitis C virus (HCV) infection. Combined therapy
with DCV and ASV shows high efficacy and safety even in patients with cirrhosis.
We encountered a patient exhibiting severe hyperbilirubinemia during combined
therapy, which is an unreported side effect of DCV and ASV. A 78-year-old woman
with cirrhosis developed hyperbilirubinemia >10 mg/dl without transaminitis 3
weeks after starting combined therapy. We suspected DAAs-induced liver disorder
and discontinued treatment, which resulted in the improvement of
hyperbilirubinemia. Caution is required in the use of DAAs for patients with
advanced cirrhosis.
PMID- 27504083
TI - Very Early Presentation of Extrahepatic Portal Vein Obstruction Causing Portal
Hypertension in an Infant: Uncertainties in the Management and Therapeutic
Limitations.
AB - Extrahepatic portal vein obstruction, although rare in children, is a significant
cause of portal hypertension (PHT) leading to life-threatening gastrointestinal
bleeding in the pediatric age group. PHT may also lead to other complications
such as hyperesplenism, cholangyopathy, ascites, and even hepatopulmonary
syndrome and portopulmonary hypertension that may require organ transplantation.
Herein we report the case of an asymptomatic 11-month-old infant wherein a
hepatomegaly and cavernous transformation of the portal vein was detected by
liver ultrasound. Neither signs of thrombosis in arteriovenous system, nor
affectation of biliary tract were identified in the magnetic resonance imaging
study. A significant enlargement of the caudate lobe of the liver was reported.
No risk factors were detected. The differential diagnosis performed was
extensive. Inherited thrombophilia and storage disorders were especially
considered. Liver biopsy was normal. Upper gastrointestinal
esophagogastroduodenoscopy detected two small varicose cords on the distal third
of the esophagus. Finding a cavernous transformation of the portal vein with
evidence of collateral circulation in such an early age is a challenging
condition for professionals, since PHT may lead to severe complications during
childhood and can compromise growth and development. Evidence-based guidelines
for the management of PHT in adults have been published. However, follow-up and
treatment of pediatric patients have not yet been standardized. Moreover,
management of PHT in infants faces particular difficulties such as technical
restrictions that could hinder their treatment.
PMID- 27504084
TI - Increased Expression of Osteopontin in Retinal Degeneration Induced by Blue Light
Emitting Diode Exposure in Mice.
AB - Osteopontin (OPN) is a multifunctional adhesive glycoprotein that is implicated
in a variety of pro-inflammatory as well as neuroprotective and repair-promoting
effects in the brain. As a first step towards understanding the role of OPN in
retinal degeneration (RD), we examined changes in OPN expression in a mouse model
of RD induced by exposure to a blue light-emitting diode (LED). RD was induced in
BALB/c mice by exposure to a blue LED (460 nm) for 2 h. Apoptotic cell death was
evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
assay. In order to investigate changes in OPN in RD, western blotting and
immunohistochemistry were performed. Anti-OPN labeling was compared to that of
anti-glial fibrillary acidic protein (GFAP), which is a commonly used marker for
retinal injury or stress including inflammation. OPN expression in RD retinas
markedly increased at 24 h after exposure, was sustained through 72 h, and
subsided at 120 h. Increased OPN expression was observed co-localized with
microglial cells in the outer nuclear layer (ONL), outer plexiform layer (OPL),
and subretinal space. Expression was restricted to the central retina in which
photoreceptor cell death occurred. Interestingly, OPN expression in the ONL/OPL
was closely associated with microglia, whereas most of the OPN plaques observed
in the subretinal space were not. Immunogold electron microscopy demonstrated
that OPN was distributed throughout the cytoplasm of microglia and in nearby
fragments of degenerating photoreceptors. In addition, we found that OPN was
induced more acutely and with greater region specificity than GFAP. These results
indicate that OPN may be a more useful marker for retinal injury or stress, and
furthermore act as a microglial pro-inflammatory mediator and a phagocytosis
inducing opsonin in the subretinal space. Taken together, our data suggest that
OPN plays an important role in the pathogenesis of RD.
PMID- 27504086
TI - Emergent Spatial Patterns of Excitatory and Inhibitory Synaptic Strengths Drive
Somatotopic Representational Discontinuities and their Plasticity in a
Computational Model of Primary Sensory Cortical Area 3b.
AB - Mechanisms underlying the emergence and plasticity of representational
discontinuities in the mammalian primary somatosensory cortical representation of
the hand are investigated in a computational model. The model consists of an
input lattice organized as a three-digit hand forward-connected to a lattice of
cortical columns each of which contains a paired excitatory and inhibitory cell.
Excitatory and inhibitory synaptic plasticity of feedforward and lateral
connection weights is implemented as a simple covariance rule and competitive
normalization. Receptive field properties are computed independently for
excitatory and inhibitory cells and compared within and across columns. Within
digit representational zones intracolumnar excitatory and inhibitory receptive
field extents are concentric, single-digit, small, and unimodal. Exclusively in
representational boundary-adjacent zones, intracolumnar excitatory and inhibitory
receptive field properties diverge: excitatory cell receptive fields are single
digit, small, and unimodal; and the paired inhibitory cell receptive fields are
bimodal, double-digit, and large. In simulated syndactyly (webbed fingers),
boundary-adjacent intracolumnar receptive field properties reorganize to within
representation type; divergent properties are reacquired following syndactyly
release. This study generates testable hypotheses for assessment of cortical
laminar-dependent receptive field properties and plasticity within and between
cortical representational zones. For computational studies, present results
suggest that concurrent excitatory and inhibitory plasticity may underlie novel
emergent properties.
PMID- 27504087
TI - Apremilast Use for Moderate-to-Severe Atopic Dermatitis in Pediatric Patients.
AB - Atopic dermatitis (AD) is a chronic, pruritic skin disease often complicated by
bacterial superinfection affecting 10.7% of American children. The pathogenesis
involves a skin barrier breakdown in addition to dysfunctional innate and
adaptive immune response, including an unbalanced increase in T-helper 2 cells
and hyperimmunoglobulinemia E. The increased numbers of T-helper 2 cells are
involved in stimulating the production of immunoglobulin E and eosinophilia by
releasing interleukin-4, -5, and -13 as well as in decreasing protection against
bacterial superinfection by releasing interleukin-10. The current Food and Drug
Administration-approved symptomatic treatment for AD includes topical ointments,
topical and systemic corticosteroids, topical immunomodulant therapy,
antibiotics, and phototherapy, but there are not approved targeted therapies or
cures. By presenting a case of an 8-year-old African-American boy, this case
report supports novel therapy of moderate-to-severe AD with apremilast, a
phosphodiesterase type 4 inhibitor. Apremilast has recently completed the phase 2
clinical trial (NCT02087943) for treatment of AD in adults. This case report
illustrates the potential for apremilast as a treatment for AD in children, where
there is a great need for safe and effective medications.
PMID- 27504085
TI - The Presynaptic Microtubule Cytoskeleton in Physiological and Pathological
Conditions: Lessons from Drosophila Fragile X Syndrome and Hereditary Spastic
Paraplegias.
AB - The capacity of the nervous system to generate neuronal networks relies on the
establishment and maintenance of synaptic contacts. Synapses are composed of
functionally different presynaptic and postsynaptic compartments. An appropriate
synaptic architecture is required to provide the structural basis that supports
synaptic transmission, a process involving changes in cytoskeletal dynamics.
Actin microfilaments are the main cytoskeletal components present at both
presynaptic and postsynaptic terminals in glutamatergic synapses. However, in the
last few years it has been demonstrated that microtubules (MTs) transiently
invade dendritic spines, promoting their maturation. Nevertheless, the presence
and functions of MTs at the presynaptic site are still a matter of debate. Early
electron microscopy (EM) studies revealed that MTs are present in the presynaptic
terminals of the central nervous system (CNS) where they interact with synaptic
vesicles (SVs) and reach the active zone. These observations have been reproduced
by several EM protocols; however, there is empirical heterogeneity in detecting
presynaptic MTs, since they appear to be both labile and unstable. Moreover,
increasing evidence derived from studies in the fruit fly neuromuscular junction
proposes different roles for MTs in regulating presynaptic function in
physiological and pathological conditions. In this review, we summarize the main
findings that support the presence and roles of MTs at presynaptic terminals,
integrating descriptive and biochemical analyses, and studies performed in
invertebrate genetic models.
PMID- 27504088
TI - A Case Of Bilateral Acquired Localized Lipoatrophy.
AB - Lipoatrophy is characterized by inflammation and tissue loss in fatty tissue.
This disease may be congenital or acquired, primary or secondary. Secondary
lipoatrophy develops with infections, collagen tissue diseases, tumors and drug
injections. In this report, we present the case of a 14-year-old female patient
who developed lipoatrophy following intramuscular steroid injection to both
buttocks.
PMID- 27504089
TI - Inframammary Dermatitis: A Case of Localized Late-Onset Darier's Disease.
AB - Darier's disease (DD) is an autosomal dominant inherited genodermatosis which is
often under- or misdiagnosed. In the majority of cases, the disease manifests in
adolescents or young adults with small brownish-yellow, warty, hyperkeratotic
papules in multiple seborrheic areas of the body. Localized DD (LDD) is a
clinical variant, first described by Kreibich in 1906; only a few cases are
reported in the literature. We described the case of an aged woman presenting
with LDD, and we review the literature on this subject.
PMID- 27504090
TI - Nodular Cutaneous Amyloidosis at the Temple.
AB - A 52-year-old woman presented with a large partially yellow and erythematous
tumor on her right temple. She reported that it had grown over the last 4 years.
Regional lymph nodes were impalpable. A punch biopsy showed eosinophilic material
in the dermis and subcutis. Immunohistochemistry showed positive staining for
kappa and lambda light chains. Electron microscopy showed the typical amyloid
fibrils (7-10 nm in diameter). There was no evidence of systemic amyloidosis,
paraproteinemia or underlying plasmacytoma. The tumor was completely removed via
curettage. At follow-up, the patient presented in good health with no signs of
relapse.
PMID- 27504091
TI - A Young Woman with Ischemic Stroke: Should We Pay More Attention to Varicella
Zoster Infection?
AB - Ischemic and hemorrhagic stroke are recognized complications of Varicella zoster
virus (VZV) infections, although uncommon and poorly documented. The authors
report the case of a 31-year-old woman admitted with acute ischemic stroke of the
right posterior cerebral artery and a history of a thoracic rash 1 month before.
Aspirin and simvastatin were prescribed, but the patient suffered a stepwise
deterioration the following days, with new areas of infarction on brain imaging.
Despite no evidence of cardiac or large vessel embolic sources, anticoagulation
was started empirically 6 days after stroke onset. One week later, symptomatic
hemorrhagic transformation occurred. The diagnosis of VZV vasculopathy was then
considered, and treatment with acyclovir and prednisolone was started with no
further vascular events. Cerebrospinal fluid analysis and digital subtraction
angiography findings corroborated the diagnosis. The patient was discharged to
the rehabilitation center with a modified Rankin scale (mRS) score of 4. On the 6
month follow-up, she presented only a slight disability (mRS score 2). In
conclusion, VZV vasculopathy needs to be considered in young adults with stroke.
A high index of suspicion and early treatment seem to be important to minimize
morbidity and mortality. Anticoagulation should probably be avoided in stroke
associated with VZV vasculopathy.
PMID- 27504092
TI - Brown Heroin-Associated Candida albicans Ventriculitis and Endophthalmitis
Treated with Voriconazole.
AB - Chronic meningitis and ventriculitis are defined as inflammatory pleocytoses in
the cerebrospinal fluid (CSF) and ependyma that persists for at least 1 month
without spontaneous resolution. Because the CSF communicates directly with the
posterior compartments of the eye, fungal infections in the brain often cause
secondary ophthalmologic complications. We report a 23-year-old male who
presented to the emergency room with progressive severe headaches associated with
insidious monocular vision loss. After extensive workup and a multidisciplinary
team effort, the patient was diagnosed with ventriculitis and endogenous
endopthalmitis. The etiology is suspected to be due to brown heroin use with
secondary disseminated Candida albicans.
PMID- 27504093
TI - Demyelinizing Neurological Disease after Treatment with Tumor Necrosis Factor
alpha Antagonists.
AB - PURPOSE: Demyelinizing neurological disease is a rare complication after
treatment with tumor necrosis factor (TNF)alpha antagonists. We report on a case
of multiple sclerosis after TNFalpha antagonist treatment and discuss its
differential diagnosis. METHODS: This is an observational case study. RESULTS: A
48-year-old male was referred to Ophthalmology in January 2015 for an absolute
scotoma in the superior quadrant of the visual field in his right eye. Visual
acuity was 20/50 in the right eye and 20/20 in the left. Fundus examination was
unremarkable bilaterally. Spectral domain optical coherence tomography revealed a
normal macular retina structure. Visual field examination revealed a superior
hemianopsia in the right eye. Head magnetic resonance imaging showed findings
compatible with optic neuritis. The visual evoked potentials confirmed the
presence of optic neuritis. The patient had been under therapy with adalimumab
since January 2014, for Crohn's disease. Suspension of adalimumab was
recommended, and it was substituted with tapered deltacortene, from 1 mg/kg/day.
After 1 month, the scotoma was resolved completely. CONCLUSIONS: TNFalpha
antagonists can provide benefit to patients with inflammatory autoimmune
diseases. However, they can also be associated with severe adverse effects.
Therefore, adequate attention should be paid to neurological abnormalities in
patients treated with TNFalpha antagonists.
PMID- 27504094
TI - A Ribonuclease Isolated from Wild Ganoderma Lucidum Suppressed Autophagy and
Triggered Apoptosis in Colorectal Cancer Cells.
AB - The mushroom Ganoderma lucidum (G. lucidum) has been consumed in China as a
medicine for promoting health and longevity for thousands of years. Due to its
paramount and multiple pharmaceutical effects, G. lucidum has received
considerable attention from researchers and its chemical constituents as well as
their respective functions were gradually unveiled by using modern research
methods. Herein, we reported the isolation of a protein (Ganoderma lucidum
ribonuclease, GLR) with anti-colorectal cancer activities from G. lucidum. This
protein is a 17.4-kDa RNA degrading enzyme (ribonuclease) and was purified by
using liquid chromatography procedures. GLR manifested potent anti-proliferative
and anti-colony formation activities on HT29 and HCT116 colorectal cancer cells
by inducing cell cycle arrest in G1 phase through the regulation of cyclin D1 and
P53 expression. GLR was demonstrated to induce cell apoptosis in HCT116 cells by
activating unfolded protein response and caspase-9 regulated pathways. Besides,
the ability to undergo autophagy which is a stress adaption mechanism to cope
with metabolic crisis was significantly suppressed by GLR treatment in HCT116
cells. The activation of apoptosis in GLR-treated HT29 cells was, however,
independent of caspase-9 and the suppression of autophagy was also relatively
minor. Thus the apoptosis of HT29 cells triggered by GLR was much milder than
that in HCT116 cells. Our findings show that the RNase from G. lucidum may be one
of the bioactive components that contribute to the anti-colorectal cancer
activity of G. lucidum.
PMID- 27504095
TI - A Standardized Chemically Modified Curcuma longa Extract Modulates IRAK-MAPK
Signaling in Inflammation and Potentiates Cytotoxicity.
AB - The TLR/IL-1R pathway is a critical signaling module that is misregulated in
pathologies like inflammation and cancer. Extracts from turmeric (Curcuma longa
L.) enriched in curcumin and carbonyls like turmerones have been shown to exert
potent anti-inflammatory effects. The present study evaluated the anti
inflammatory activity, cytotoxic effect and the underlying mechanism of a novel
chemically modified, non-carbonyl compound enriched Curcuma longa L. (C. longa)
extract (CMCE). CMCE (1 or 10 MUg/mL; 14 h) significantly decreased LPS (50-100
ng/mL) induced TNF-alpha and IL-1beta production in THP-1 cells, human, and mouse
whole blood as measured by ELISA. LPS-induced IRAK1, MAPK activation, TLR4
expression, TLR4-MyD88 interaction, and IkappaBalpha degradation were
significantly reduced in CMCE pre-treated THP-1 cells as assessed by Western
blotting. CMCE (30, 100, and 300 mg/kg; 10 days p.o.) pre-treated and LPS (10
mg/kg) challenged Swiss mice exhibited attenuated plasma TNF-alpha, IL-1beta,
nitrite, aortic iNOS expression, and vascular dysfunction. In a PI permeability
assay, cell lines derived from acute myeloid leukemia were most sensitive to the
cytotoxic effects of CMCE. Analysis of Sub-G1 phase, Annexin V-PI positivity,
loss of mitochondrial membrane potential, increased caspase-3, and PARP-1
activation confirmed CMCE induced apoptosis in HL-60 cells. IRAK inhibition also
sensitized HL-60 cells to CMCE induced cytotoxicity. The present study defines
the mechanism underlying the action of CMCE and suggests a therapeutic potential
for its use in sepsis and leukemia.
PMID- 27504096
TI - Protective Effects of Otophylloside N on Pentylenetetrazol-Induced Neuronal
Injury In vitro and In vivo.
AB - Approximately 30% of epileptic patients worldwide are medically unable to control
their seizures. In addition, repeated epileptic seizures generally lead to neural
damage. Pentylenetetrazol (PTZ) is a clinical circulatory and respiratory
stimulant that is experimentally used to mimic epileptic convulsion in epilepsy
research. Here, we systematically explore the neuroprotective effects of a pure
compound isolated from Cynanchum otophyllum Schneid (Qingyangshen), Otophylloside
N (OtoN), against PTZ-induced neuronal injury. We used three models: in vitro
primary cortical neurons, in vivo mice, and in vivo zebrafish. Our results
revealed that OtoN treatment may attenuate PTZ-induced morphology changes, cell
death, LDH efflux in embryonic neuronal cells of C57BL/6J mice, and convulsive
behavior in zebrafish. Additionally, our Western blot and RT-PCR results
demonstrated that OtoN may attenuate PTZ-induced apoptosis and neuronal
activation in neuronal cells, mice, and zebrafish. OtoN may reduce PTZ-induced
cleavage of poly ADP-ribose polymerase and upregulation of the Bax/Bcl-2 ratio
and decrease the expression level of c-Fos. This study is the first investigation
of the neuroprotective effects of OtoN, which might be developed as a novel
antiepileptic drug.
PMID- 27504097
TI - Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High
Aerobic Capacity.
AB - The production of heat, i.e., thermogenesis, is a significant component of the
metabolic rate, which in turn affects weight gain and health. Thermogenesis is
linked to physical activity (PA) level. However, it is not known whether
intrinsic exercise capacity, aging, and long-term voluntary running affect core
body temperature. Here we use rat models selectively bred to differ in maximal
treadmill endurance running capacity (Low capacity runners, LCR and High capacity
Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging,
and metabolic disease risk to study the connection between PA and body
temperature. Ten high capacity runner (HCR) and ten low capacity runner (LCR)
female rats were studied between 9 and 21 months of age. Rectal body temperature
of HCR and LCR rats was measured before and after 1-year voluntary
running/control intervention to explore the effects of aging and PA. Also, we
determined whether injected glucose and spontaneous activity affect the body
temperature differently between LCR and HCR rats at 9 vs. 21 months of age. HCRs
had on average 1.3 degrees C higher body temperature than LCRs (p < 0.001). Aging
decreased the body temperature level of HCRs to similar levels with LCRs. The
opportunity to run voluntarily had a significant impact on the body temperature
of HCRs (p < 0.001) allowing them to maintain body temperature at a similar level
as when at younger age. Compared to LCRs, HCRs were spontaneously more active,
had higher relative gastrocnemius muscle mass and higher UCP2, PGC-1alpha, cyt c,
and OXPHOS levels in the skeletal muscle (p < 0.050). These results suggest that
higher PA level together with greater relative muscle mass and higher
mitochondrial content/function contribute to the accumulation of heat in the
HCRs. Interestingly, neither aging nor voluntary training had a significant
impact on core body temperature of LCRs. However, glucose injection resulted in a
lowering of the body temperature of LCRs (p < 0.050), but not that of HCRs. In
conclusion, rats born with high intrinsic capacity for aerobic exercise and
better health have higher body temperature compared to rats born with low
exercise capacity and disease risk. Voluntary running allowed HCRs to maintain
high body temperature during aging, which suggests that high PA level was crucial
in maintaining the high body temperature of HCRs.
PMID- 27504099
TI - Quality of Life in Caregivers of ADHD Children and Diabetes Patients.
AB - INTRODUCTION: Studies have shown that the presence of attention-deficit
hyperactivity disorder (ADHD) causes great impairment in academic, social, and
professional activities as well as in the quality of life (QoL) of its patients.
Similarly, the impact caused by other chronic disorders, such as diabetes, in the
patient's QoL has been emphasized in many studies. Despite its relevance, no
study has yet investigated whether ADHD caregivers and diabetic patients would
have similar QoL impairment. OBJECTIVES: This study was conducted in order to
compare the QoL scores among ADHD caregivers and diabetic patients. METHODS: We
evaluated 63 caregivers of ADHD children treated at the Child and Adolescent
Psychiatric Unit at the Federal University of Sao Paulo (UPIA-UNIFESP) and 52
adult diabetic patients. Subjects were assessed with the World Health
Organization quality of Life-Bref Version (WHOQOL-BREF), the Beck and Hamilton
depression scales, and the Adult Self-Report Scale. RESULTS: When compared to the
Brazilian normative data, ADHD caregivers had significantly lower scores in the
social relations and environment WHOQOL domains. ADHD caregivers and diabetic
patients had similar impairment in all WHOQOL domains except for the physical
domain. CONCLUSION: ADHD affects the QoL of the patient's caregiver, with similar
impairment, when compared to the QoL of diabetic patients. These results
emphasize the need for assessing QoL of the caregivers as part of the treatment
strategies. They also emphasize the need for future studies with larger sample
sizes comparing how the QOL is impacted in different chronic disorders.
PMID- 27504098
TI - Can Interoception Improve the Pragmatic Search for Biomarkers in Psychiatry?
AB - Disrupted interoception is a prominent feature of the diagnostic classification
of several psychiatric disorders. However, progress in understanding the
interoceptive basis of these disorders has been incremental, and the application
of interoception in clinical treatment is currently limited to panic disorder. To
examine the degree to which the scientific community has recognized interoception
as a construct of interest, we identified and individually screened all articles
published in the English language on interoception and associated root terms in
Pubmed, Psychinfo, and ISI Web of Knowledge. This search revealed that
interoception is a multifaceted process that is being increasingly studied within
the fields of psychiatry, psychology, neuroscience, and biomedical science. To
illustrate the multifaceted nature of interoception, we provide a focused review
of one of the most commonly studied interoceptive channels, the cardiovascular
system, and give a detailed comparison of the most popular methods used to study
cardiac interoception. We subsequently review evidence of interoceptive
dysfunction in panic disorder, depression, somatic symptom disorders, anorexia
nervosa, and bulimia nervosa. For each disorder, we suggest how interoceptive
predictions constructed by the brain may erroneously bias individuals to express
key symptoms and behaviors, and outline questions that are suitable for the
development of neuroscience-based mental health interventions. We conclude that
interoception represents a viable avenue for clinical and translational research
in psychiatry, with a well-established conceptual framework, a neural basis,
measurable biomarkers, interdisciplinary appeal, and transdiagnostic targets for
understanding and improving mental health outcomes.
PMID- 27504101
TI - Comparing Emotion Recognition Skills among Children with and without Jailed
Parents.
AB - Approximately five million children in the United States have experienced a co
resident parent's incarceration in jail or prison. Parental incarceration is
associated with multiple risk factors for maladjustment, which may contribute to
the increased likelihood of behavioral problems in this population. Few studies
have examined early predictors of maladjustment among children with incarcerated
parents, limiting scholars' understanding about potential points for prevention
and intervention. Emotion recognition skills may play a role in the development
of maladjustment and may be amenable to intervention. The current study examined
whether emotion recognition skills differed between 3- to 8-year-old children
with and without jailed parents. We hypothesized that children with jailed
parents would have a negative bias in processing emotions and less accuracy
compared to children without incarcerated parents. Data were drawn from 128
families, including 75 children (53.3% male, M = 5.37 years) with jailed parents
and 53 children (39.6% male, M = 5.02 years) without jailed parents. Caregivers
in both samples provided demographic information. Children performed an emotion
recognition task in which they were asked to produce a label for photos
expressing six different emotions (i.e., happy, surprised, neutral, sad, angry,
and fearful). For scoring, the number of positive and negative labels were
totaled; the number of negative labels provided for neutral and positive stimuli
were totaled (measuring negative bias/overextension of negative labels); and
valence accuracy (i.e., positive, negative, and neutral) and label accuracy were
calculated. Results indicated a main effect of parental incarceration on the
number of positive labels provided; children with jailed parents presented
significantly fewer positive emotions than the comparison group. There was also a
main effect of parental incarceration on negative bias (the overextension of
negative labels); children with jailed parents had a negative bias compared to
children without jailed parents. However, these findings did not hold when
controlling for child age, race/ethnicity, receipt of special education services,
and caregiver education. The results provide some evidence for the effect of the
context of parental incarceration in the development of negative emotion
recognition biases. Limitations and implications for future research and
interventions are discussed.
PMID- 27504100
TI - Multivariate Imaging Genetics Study of MRI Gray Matter Volume and SNPs Reveals
Biological Pathways Correlated with Brain Structural Differences in Attention
Deficit Hyperactivity Disorder.
AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent
neurodevelopmental disorder affecting children, adolescents, and adults. Its
etiology is not well understood, but it is increasingly believed to result from
diverse pathophysiologies that affect the structure and function of specific
brain circuits. Although one of the best-studied neurobiological abnormalities in
ADHD is reduced fronto-striatal-cerebellar gray matter (GM) volume, its specific
genetic correlates are largely unknown. METHODS: In this study, T1-weighted MR
images of brain structure were collected from 198 adolescents (63 ADHD
diagnosed). A multivariate parallel independent component analysis (Para-ICA)
technique-identified imaging genetic relationships between regional GM volume and
single nucleotide polymorphism data. RESULTS: Para-ICA analyses extracted 14
components from genetic data and 9 from MR data. An iterative cross-validation
using randomly chosen subsamples indicated acceptable stability of these ICA
solutions. A series of partial correlation analyses controlling for age, sex, and
ethnicity revealed two genotype-phenotype component pairs significantly differed
between ADHD and non-ADHD groups, after a Bonferroni correction for multiple
comparisons. The brain phenotype component not only included structures
frequently found to have abnormally low volume in previous ADHD studies but was
also significantly associated with ADHD differences in symptom severity and
performance on cognitive tests frequently found to be impaired in patients
diagnosed with the disorder. Pathway analysis of the genotype component
identified several different biological pathways linked to these structural
abnormalities in ADHD. CONCLUSION: Some of these pathways implicate well-known
dopaminergic neurotransmission and neurodevelopment hypothesized to be abnormal
in ADHD. Other more recently implicated pathways included glutamatergic and GABA
eric physiological systems; others might reflect sources of shared liability to
disturbances commonly found in ADHD, such as sleep abnormalities.
PMID- 27504102
TI - Reducing the Meta-Emotional Problem Decreases Physiological Fear Response during
Exposure in Phobics.
AB - Anxiety disorders may not only be characterized by specific symptomatology (e.g.,
tachycardia) in response to the fearful stimulus (primary problem or first-level
emotion) but also by the tendency to negatively evaluate oneself for having those
symptoms (secondary problem or negative meta-emotion). An exploratory study was
conducted driven by the hypothesis that reducing the secondary or meta-emotional
problem would also diminish the fear response to the phobic stimulus. Thirty
three phobic participants were exposed to the phobic target before and after
undergoing a psychotherapeutic intervention addressed to reduce the meta
emotional problem or a control condition. The electrocardiogram was continuously
recorded to derive heart rate (HR) and heart rate variability (HRV) and affect
ratings were obtained. Addressing the meta-emotional problem had the effect of
reducing the physiological but not the subjective symptoms of anxiety after
phobic exposure. Preliminary findings support the role of the meta-emotional
problem in the maintenance of response to the fearful stimulus (primary problem).
PMID- 27504103
TI - Contribution of Pro-inflammatory Cytokine Signaling within Midbrain
Periaqueductal Gray to Pain Sensitivity in Parkinson's Disease via GABAergic
Pathway.
AB - BACKGROUND/AIMS: Hypersensitive pain response is often observed in patients with
Parkinson's disease (PD); however, the mechanisms responsible for hyperalgesia
are not well understood. Chronic neuroinflammation is one of the hallmarks of PD
pathophysiology. Since the midbrain periaqueductal gray (PAG) is an important
component of the descending inhibitory pathway controlling on central pain
transmission, we examined the role for pro-inflammatory cytokines (PICs) system
of PAG in regulating exaggerated pain evoked by PD. METHODS: We used a rat model
of PD to perform the experimental protocols. PD was induced by microinjection of
6-hydroxydopamine to lesion the left medial forebrain bundle. Pain responses to
mechanical and thermal stimulation were first examined in control rats and PD
rats. Then, ELISA and Western Blot analysis were used to determine PIC levels and
their receptors expression. RESULTS: Protein expression of IL-1beta, IL-6, and
TNF-alpha receptors (namely, IL-1R, IL-6R, and TNFR subtype TNFR1) in the plasma
membrane PAG of PD rats was upregulated, whereas the total expression of PIC
receptors was not significantly altered. The ratio of membrane protein and total
protein (IL-1R, IL-6R, and TNFR1) was 1.48 +/- 0.15, 1.59 +/- 0.18, and 1.67 +/-
0.16 in PAG of PD rats (P < 0.05 vs. their respective controls). This was
accompanied with increases of PICs of PAG and decreases of GABA (623 +/- 21 ng/mg
in control rats and 418 +/- 18 ng/mg in PD rats; P < 0.05 vs. control rats) and
withdrawal thresholds to mechanical and thermal stimuli. Our data further showed
that the concentrations of GABA and withdrawal thresholds were largely restored
by blocking those PIC receptors in PAG of PD rats. Stimulation of GABA receptors
in PAG of PD rats also blunted a decrease in withdrawal thresholds. CONCLUSION:
Our data suggest that upregulation of the membrane PIC receptor in the PAG of PD
rats is likely to impair the descending inhibitory pathways in regulating pain
transmission and thereby plays a role in the development of hypersensitive pain
response in PD.
PMID- 27504104
TI - Functional Connectivity Is Altered in Concussed Adolescent Athletes Despite
Medical Clearance to Return to Play: A Preliminary Report.
AB - Recovery following sports-related concussion (SRC) is slower and often more
complicated in young adolescent athletes than in collegiate players. Further, the
clinical decision to return to play is currently based on symptoms and cognitive
performance without direct knowledge of brain function. We tested the hypothesis
that brain functional connectivity (FC) would be aberrant in recently concussed,
asymptomatic athletes who had been cleared to return to play. A seed-based FC
analysis measured the FC of the default mode network (DMN) (seeds = anterior
cingulate cortex, posterior cingulate cortex (PCC), right lateral parietal
cortex, and left lateral parietal cortex) 30 days after SRC in asymptomatic high
school athletes cleared to return to play (n = 13) and was compared to the FC of
high school athletes with orthopedic injury (OI) (n = 13). The SRC group
demonstrated greater FC than the OI group between the PCC and the ventral lateral
prefrontal cortex, as well as between the right lateral parietal cortex and
lateral temporal cortex (with regions both outside of and within the DMN).
Additionally, the OI group demonstrated greater FC than the SRC group between
right lateral parietal cortex and supramarginal gyrus. When relating the FC
results to verbal memory performance approximately 1 week and 1 month after
injury, significantly different between-group relations were found for the
posterior cingulate and right lateral parietal cortex seeds. However, the groups
did not differ in verbal memory at 1 month. We suggest that changes in FC are
apparent 1-month post-SRC despite resolution of post-concussion symptoms and
recovery of cognitive performance in adolescent athletes cleared to return to
play.
PMID- 27504105
TI - Non-Motor Symptoms in Patients Suffering from Motor Neuron Diseases.
AB - BACKGROUND: The recently postulated "disease spreading hypothesis" has gained
much attention, especially for Parkinson's disease (PD). The various non-motor
symptoms (NMS) in neurodegenerative diseases would be much better explained by
this hypothesis than by the degeneration of disease-specific cell populations.
Motor neuron disease (MND) is primarily known as a group of diseases with a
selective loss of motor function. However, recent evidence suggests disease
spreading into non-motor brain regions also in MND. The aim of this study was to
comprehensively detect NMS in patients suffering from MND. METHODS: We used a
self-rating questionnaire including 30 different items of gastrointestinal,
autonomic, neuropsychiatric, and sleep complaints [NMS questionnaire (NMSQuest)],
which is an established tool in PD patients. 90 MND patients were included and
compared to 96 controls. RESULTS: In total, MND patients reported significantly
higher NMS scores (median: 7 points) in comparison to controls (median: 4
points). Dribbling, impaired taste/smelling, impaired swallowing, weight loss,
loss of interest, sad/blues, falling, and insomnia were significantly more
prevalent in MND patients compared to controls. Interestingly, excessive sweating
was more reported in the MND group. Correlation analysis revealed an increase of
total NMS score with disease progression. CONCLUSION: NMS in MND patients seemed
to increase with disease progression, which would fit with the recently
postulated "disease spreading hypothesis." The total NMS score in the MND group
significantly exceeded the score for the control group, but only 8 of the 30
single complaints of the NMSQuest were significantly more often reported by MND
patients. Dribbling, impaired swallowing, weight loss, and falling could
primarily be connected to motor neuron degeneration and declared as motor
symptoms in MND.
PMID- 27504106
TI - Prognostic Factors for Adrenocortical Carcinoma Outcomes.
AB - PURPOSE: Adrenocortical carcinoma (ACC) is an aggressive tumor characterized by a
high recurrence rate and poor response to treatment. This study analyzes a
consecutive series of ACC patients to evaluate the prognostic value of various
clinical and pathological characteristics. METHODS: We retrospectively evaluated
32 ACC patients followed at our Medical Center from 1997 to 2015 and evaluated
the prognostic value of age at diagnosis, gender, tumor functional status, stage,
and type of treatment with respect to overall survival (OS) and disease-free
survival (DFS), as determined by Kaplan-Meier curves. RESULTS: ACC was associated
with hormonal overproduction in 50% of cases, and patients with isolated
hyperandrogenism had a better prognosis. Recurrence was observed in 12/26 (46.2%)
patients with no evidence of disease after surgery. Tumor size [hazard ratio (HR)
1.32, 95% confidential intervals (CI) 1.12-1.64; p = 0.007], ki-67 (HR 1.06, 95%
CI 1.02-1.11; p = 0.009) and advanced stage at diagnosis (III-IV) (HR 6.51, 95%
CI 1.65-24.68; p = 0.006) were associated with recurrence in the 26 R0 patients
in the univariate analysis. Advanced stage was an independent risk factor for
recurrence in the multivariate analysis (HR 8.10, 95% CI 1.55-41.35; p = 0.01).
Five-year survival was 40.0%. Positive resection margins (HR 10.61, 95% CI 3.02
38.31; p = < 0.001), ki-67 (HR 1.04, 95% CI 1.01-1.07; p = 0.01) and advanced
stage (HR 11.31, 95% CI 1.45-87.76; p = 0.02) were associated with poor survival
in all 32 patients, but only positive resection margins were an independent
predictor of mortality in the multivariate analysis (HR 6.22, 95% CI 1.44-26.05;
p = 0.01). CONCLUSION: ACC has a poor prognosis with a high recurrence rate.
Tumor stage at diagnosis and the completeness of surgical excision are the most
relevant prognostic factors.
PMID- 27504107
TI - Bioassays for TSH Receptor Autoantibodies, from FRTL-5 Cells to TSH Receptor
LH/CG Receptor Chimeras: The Contribution of Leonard D. Kohn.
AB - Since the discovery 60 years ago of the "long-acting thyroid stimulator" by Adams
and Purves, great progress has been made in the detection of thyroid-stimulating
hormone (TSH) receptor (TSHR) autoantibodies (TRAbs) in Graves' disease. Today,
commercial assays are available that can detect TRAbs with high accuracy and
provide diagnostic and prognostic evaluation of patients with Graves' disease.
The present review focuses on the development of TRAbs bioassays, and
particularly on the role that Leonard D. Kohn had in this. Indeed, 30 years ago,
the Kohn group developed a bioassay based on the use of FRTL-5 cells that was
characterized by high reproducibility, feasibility, and diagnostic accuracy.
Using this FRTL-5 bioassay, Kohn and his colleagues were the first to develop
monoclonal antibodies (moAbs) against the TSHR. Furthermore, they demonstrated
the multifaceted functional nature of TRAbs in patients with Graves' disease,
with the identification of stimulating and blocking TRAbs, and even antibodies
that activated pathways other than cAMP. After the cloning of the TSHR, the Kohn
laboratory constructed human TSHR-rat luteinizing hormone/chorionic gonadotropin
receptor chimeras. This paved the way to a new bioassay based on the use of non
thyroid cells transfected with the Mc4 chimera. The new Mc4 bioassay is
characterized by high diagnostic and prognostic accuracy, greater than for other
assays. The availability of a commercial kit based on the Mc4 chimera is
spreading the use of this assay worldwide, indicating its benefits for these
patients with Graves' disease. This review also describes the main contributions
made by other researchers in TSHR molecular biology and TRAbs assay, especially
with the development of highly potent moAbs. A comparison of the diagnostic
accuracies of the main TRAbs assays, as both immunoassays and bioassays, is also
provided.
PMID- 27504108
TI - Silver Nanoparticles, Ions, and Shape Governing Soil Microbial Functional
Diversity: Nano Shapes Micro.
AB - Silver nanoparticles (AgNPs) affect microbial metabolic processes at single cell
level or lab-culture strains. However, the impact of different AgNPs properties
such as the particle, ion release, and shape on functional responses of natural
soil microbial communities remain poorly understood. Therefore, we assessed the
relative importance of particles and ions of AgNPs in bacterial toxicity and how
the functional diversity of soil microbial communities were impacted by AgNPs
shapes (i.e., plates, spheres, and rods) in laboratory incubations. Our results
showed that the relative contribution of AgNPs(particle) increased with
increasing exposure concentrations (accounted for about 60-68% of the total
toxicity at the highest exposure level). In addition, the functional composition
of the microbial community differed significantly according to different AgNPs
shapes. The various properties of AgNPs thus can significantly and differentially
affect the functional composition of microbial communities and associated
ecosystem processes depending on the level of environmental exposure.
PMID- 27504109
TI - Fermented Foods: Are They Tasty Medicines for Helicobacter pylori Associated
Peptic Ulcer and Gastric Cancer?
AB - More than a million people die every year due to gastric cancer and peptic ulcer.
Helicobacter pylori infection in stomach is the most important reason for these
diseases. Interestingly, only 10-20% of the H. pylori infected individuals suffer
from these gastric diseases and rest of the infected individuals remain
asymptomatic. The genotypes of H. pylori, host genetic background, lifestyle
including smoking and diet may determine clinical outcomes. People from different
geographical regions have different food habits, which also include several
unique fermented products of plant and animal origins. When consumed raw, the
fermented foods bring in fresh inocula of microbes to gastrointestinal tract and
several strains of these microbes, like Lactobacillus and Saccharomyces are known
probiotics. In vitro and in vivo experiments as well as clinical trials suggest
that several probiotics have anti-H. pylori effects. Here we discuss the
possibility of using natural probiotics present in traditional fermented food and
beverages to obtain protection against H. pylori induced gastric diseases.
PMID- 27504110
TI - Leukocyte Ig-Like Receptors - A Model for MHC Class I Disease Associations.
AB - MHC class I (MHC-I) polymorphisms are associated with the outcome of some viral
infections and autoimmune diseases. MHC-I proteins present antigenic peptides and
are recognized by receptors on natural killer cells and cytotoxic T lymphocytes,
thus enabling the immune system to detect self-antigens and eliminate targets
lacking self or expressing foreign antigens. Recognition of MHC-I, however,
extends beyond receptors on cytotoxic leukocytes. Members of the leukocyte Ig
like receptor (LILR) family are expressed on monocytic cells and can recognize
both classical and non-classical MHC-I alleles. Despite their relatively broad
specificity when compared to the T cell receptor or killer Ig-like receptors,
variations in the strength of LILR binding between different MHC-I alleles have
recently been shown to correlate with control of HIV infection. We suggest that
LILR recognition may mediate MHC-I disease association in a manner that does not
depend on a binary discrimination of self/non-self by cytotoxic cells. Instead,
the effects of LILR activity following engagement by MHC-I may represent a
"degrees of self" model, whereby strength of binding to different alleles
determines the degree of influence exerted by these receptors on immune cell
functions. LILRs are expressed by myelomonocytic cells and lymphocytes, extending
their influence across antigen-presenting cell subsets including dendritic cells,
macrophages, and B cells. They have been identified as important players in the
response to infection, inflammatory diseases, and cancer, with recent literature
to indicate that MHC-I recognition by these receptors and consequent allelic
effects could extend an influence beyond the immune system.
PMID- 27504111
TI - Habitat Temperature and Precipitation of Arabidopsis thaliana Ecotypes Determine
the Response of Foliar Vasculature, Photosynthesis, and Transpiration to Growth
Temperature.
AB - Acclimatory adjustments of foliar vascular architecture, photosynthetic capacity,
and transpiration rate in Arabidopsis thaliana ecotypes (Italian, Polish [Col-0],
Swedish) were characterized in the context of habitat of origin. Temperatures of
the habitat of origin decreased linearly with increasing habitat latitude, but
habitat precipitation was greatest in Italy, lowest in Poland, and intermediate
in Sweden. Plants of the three ecotypes raised under three different growth
temperature regimes (low, moderate, and high) exhibited highest photosynthetic
capacities, greatest leaf thickness, highest chlorophyll a/b ratio and levels of
beta-carotene, and greatest levels of wall ingrowths in phloem transfer cells,
and, in the Col-0 and Swedish ecotypes, of phloem per minor vein in plants grown
at the low temperature. In contrast, vein density and minor vein tracheary to
sieve element ratio increased with increasing growth temperature - most strongly
in Col-0 and least strongly in the Italian ecotype - and transpirational water
loss correlated with vein density and number of tracheary elements per minor
vein. Plotting of these vascular features as functions of climatic conditions in
the habitat of origin suggested that temperatures during the evolutionary history
of the ecotypes determined acclimatory responses of the foliar phloem and
photosynthesis to temperature in this winter annual that upregulates
photosynthesis in response to lower temperature, whereas the precipitation
experienced during the evolutionary history of the ecotypes determined adjustment
of foliar vein density, xylem, and transpiration to temperature. In particular,
whereas photosynthetic capacity, leaf thickness, and foliar minor vein phloem
features increased linearly with increasing latitude and decreasing temperature
of the habitats of origin in response to experimental growth at low temperature,
transpiration rate, foliar vein density, and minor vein tracheary element numbers
and cross-sectional areas increased linearly with decreasing precipitation level
in the habitats of origin in response to experimental growth at high temperature.
This represents a situation where temperature acclimation of the apparent
capacity for water flux through the xylem and transpiration rate in a winter
annual responded differently from that of photosynthetic capacity, in contrast to
previous reports of strong relationships between hydraulic conductance and
photosynthesis in other studies.
PMID- 27504112
TI - Multi-Scale Characean Experimental System: From Electrophysiology of Membrane
Transporters to Cell-to-Cell Connectivity, Cytoplasmic Streaming and Auxin
Metabolism.
AB - The morphology of characean algae could be mistaken for a higher plant: stem-like
axes with leaf-like branchlets anchored in the soil by root-like rhizoids.
However, all of these structures are made up of giant multinucleate cells
separated by multicellular nodal complexes. The excised internodal cells survive
long enough for the nodes to give rise to new thallus. The size of the internodes
and their thick cytoplasmic layer minimize impalement injury and allow specific
micro-electrode placement. The cell structure can be manipulated by
centrifugation, perfusion of cell contents or creation of cytoplasmic droplets,
allowing access to both vacuolar and cytoplasmic compartments and both sides of
the cell membranes. Thousands of electrical measurements on intact or altered
cells and cytoplasmic droplets laid down basis to modern plant electrophysiology.
Furthermore, the giant internodal cells and whole thalli facilitate research into
many other plant properties. As nutrients have to be transported from rhizoids to
growing parts of the thallus and hormonal signals need to pass from cell to cell,
Characeae possess very fast cytoplasmic streaming. The mechanism was resolved in
the characean model. Plasmodesmata between the internodal cells and nodal
complexes facilitate transport of ions, nutrients and photosynthates across the
nodes. The internal structure was found to be similar to those of higher plants.
Recent experiments suggest a strong circadian influence on metabolic pathways
producing indole-3-acetic acid (IAA) and serotonin/melatonin. The review will
discuss the impact of the characean models arising from fragments of cells,
single cells, cell-to-cell transport or whole thalli on understanding of plant
evolution and physiology.
PMID- 27504113
TI - Water Deficit Affects Primary Metabolism Differently in Two Lolium
multiflorum/Festuca arundinacea Introgression Forms with a Distinct Capacity for
Photosynthesis and Membrane Regeneration.
AB - Understanding how plants respond to drought at different levels of cell
metabolism is an important aspect of research on the mechanisms involved in
stress tolerance. Furthermore, a dissection of drought tolerance into its crucial
components by the use of plant introgression forms facilitates to analyze this
trait more deeply. The important components of plant drought tolerance are the
capacity for photosynthesis under drought conditions, and the ability of cellular
membrane regeneration after stress cessation. Two closely related introgression
forms of Lolium multiflorum/Festuca arundinacea, differing in the level of
photosynthetic capacity during stress, and in the ability to regenerate their
cellular membranes after stress cessation, were used as forage grass models in a
primary metabolome profiling and in an evaluation of chloroplast 1,6-bisphosphate
aldolase accumulation level and activity, during 11 days of water deficit,
followed by 10 days of rehydration. It was revealed here that the introgression
form, characterized by the ability to regenerate membranes after rehydration,
contained higher amounts of proline, melibiose, galactaric acid, myo-inositol and
myo-inositol-1-phosphate involved in osmoprotection and stress signaling under
drought. Moreover, during the rehydration period, this form also maintained
elevated accumulation levels of most the primary metabolites, analyzed here. The
other introgression form, characterized by the higher capacity for
photosynthesis, revealed a higher accumulation level and activity of chloroplast
aldolase under drought conditions, and higher accumulation levels of most
photosynthetic products during control and drought periods. The potential impact
of the observed metabolic alterations on cellular membrane recovery after stress
cessation, and on a photosynthetic capacity under drought conditions in grasses,
are discussed.
PMID- 27504114
TI - GmCLC1 Confers Enhanced Salt Tolerance through Regulating Chloride Accumulation
in Soybean.
AB - The family of chloride channel proteins that mediate Cl(-) transportation play
vital roles in plant nutrient supply, cellular action potential and turgor
pressure adjustment, stomatal movement, hormone signal recognition and
transduction, Cl(-) homeostasis, and abiotic and biotic stress tolerance. The
anionic toxicity, mainly caused by chloride ions (Cl(-)), on plants under salt
stress remains poorly understood. In this work, we investigated the function of
soybean Cl(-)/H(+) antiporter GmCLC1 under salt stress in transgenic Arabidopsis
thaliana, soybean, and yeast. We found that GmCLC1 enhanced salt tolerance in
transgenic A. thaliana by reducing the Cl(-) accumulation in shoots and hence
released the negative impact of salt stress on plant growth. Overexpression of
GmCLC1 in the hairy roots of soybean sequestered more Cl(-) in their roots and
transferred less Cl(-) to their shoots, leading to lower relative electrolyte
leakage values in the roots and leaves. When either the soybean GmCLC1 or the
yeast chloride transporter gene, GEF1, was transformed into the yeast gef1
mutant, and then treated with different chloride salts (MnCl2, KCl, NaCl),
enhanced survival rate was observed. The result indicates that GmCLC1 and GEF1
exerted similar effects on alleviating the stress of diverse chloride salts on
the yeast gef1 mutant. Together, this work suggests a protective function of
GmCLC1 under Cl(-) stress.
PMID- 27504115
TI - Comprehensive Analysis of the Triterpenoid Saponins Biosynthetic Pathway in
Anemone flaccida by Transcriptome and Proteome Profiling.
AB - BACKGROUND: Anemone flaccida Fr. Shmidt (Ranunculaceae), commonly known as 'Di
Wu' in China, is a perennial herb with limited distribution. The rhizome of A.
flaccida has long been used to treat arthritis as a tradition in China. Studies
disclosed that the plant contains a rich source of triterpenoid saponins.
However, little is known about triterpenoid saponins biosynthesis in A. flaccida.
RESULTS: In this study, we conducted the tandem transcriptome and proteome
profiling of a non-model medicinal plant, A. flaccida. Using Illumina HiSeq 2000
sequencing and iTRAQ technique, a total of 46,962 high-quality unigenes were
obtained with an average sequence length of 1,310 bp, along with 1473 unique
proteins from A. flaccida. Among the A. flaccida transcripts, 36,617 (77.97%)
showed significant similarity (E-value < 1e (-5)) to the known proteins in the
public database. Of the total 46,962 unigenes, 36,617 open reading frame (ORFs)
were predicted. By the fragments per kilobases per million reads (FPKM)
statistics, 14,004 isoforms/unigenes were found to be upregulated, and 14,090
isoforms/unigenes were down-regulated in the rhizomes as compared to those in the
leaves. Based on the bioinformatics analysis, all possible enzymes involved in
the triterpenoid saponins biosynthetic pathway of A. flaccida were identified,
including cytosolic mevalonate pathway (MVA) and the plastidial methylerythritol
pathway (MEP). Additionally, a total of 126 putative cytochrome P450 (CYP450) and
32 putative UDP glycosyltransferases were selected as the candidates of
triterpenoid saponins modifiers. Among them, four of them were annotated as the
gene of CYP716A subfamily, the key enzyme in the oleanane-type triterpenoid
saponins biosynthetic pathway. Furthermore, based on RNA-Seq and proteome
analysis, as well as quantitative RT-PCR verification, the expression level of
gene and protein committed to triterpenoids biosynthesis in the leaf versus the
rhizome was compared. CONCLUSION: A combination of the de novo transcriptome and
proteome profiling based on the Illumina HiSeq 2000 sequencing platform and iTRAQ
technique was shown to be a powerful method for the discovery of candidate genes,
which encoded enzymes that were responsible for the biosynthesis of novel
secondary metabolites in a non-model plant. The transcriptome data of our study
provides a very important resource for the understanding of the triterpenoid
saponins biosynthesis of A. flaccida.
PMID- 27504116
TI - The Diagnostic Utility of the NINDS-CSN Neuropsychological Battery in Memory
Clinics.
AB - AIMS: To examine the diagnostic utility of the National Institute of Neurological
Disorders and Stroke and the Canadian Stroke Network (NINDS-CSN)
neuropsychological battery in memory clinics comparing controls with patients
with no cognitive impairment (NCI), patients with cognitive impairment-no
dementia (CIND) at varying severity levels (mild/moderate), and patients with
dementia. METHODS: A total of 405 participants with NCI, CIND or dementia were
assessed with the NINDS-CSN battery. The discriminatory properties of all three
protocols (5, 30 and 60 min) before and after education stratification
(none/primary vs. secondary/above) were examined by receiver operating
characteristic curves. RESULTS: Overall, the shorter protocols are equivalent to
the longer protocol in diagnosing dementia, regardless of education. To
discriminate between nondementia groups, before education stratification, the 5
min protocol showed varied discriminatory properties between different
diagnostic/severity groups. After stratification, the 5-min protocol was broadly
equivalent to the longer protocols in lower-education groups [area under the
curve (AUC) range: 0.77-0.87] but was less accurate in the higher-education
groups (AUC range: 0.68-0.78). The 30- and 60-min protocol constantly showed
moderate-to-excellent differentiating capacities regardless of education (AUC
range: 0.80-0.90). CONCLUSION: The NINDS-CSN neuropsychological battery can be
applied in memory clinics and effectively discriminate between cognitively intact
individuals and those with cognitive impairments of varying severity.
Furthermore, level of education should be taken into consideration when choosing
protocols with different lengths for cognitive assessment.
PMID- 27504117
TI - Increased Cerebrospinal Fluid Levels of Ubiquitin Carboxyl-Terminal Hydrolase L1
in Patients with Alzheimer's Disease.
AB - BACKGROUND: Dysfunctions of the ubiquitin proteasome system (UPS), including the
highly abundant neuronal enzyme ubiquitin carboxyl-terminal hydrolase L1 (UCH
L1), and autophagy-related changes (lysosomal degradation) are implicated in
several neurodegenerative disorders including Alzheimer's disease (AD). METHOD:
This study evaluated cerebrospinal fluid (CSF) levels of UCH-L1, protein
deglycase (DJ-1), neuron-specific enolase (NSE), and tau phosphorylated at
threonine 231 (P-tau231) in two independent patient and control cohorts. Cohort 1
included CSF samples from subjects having an AD biomarker profile (n = 10) or a
control biomarker profile (n = 31), while cohort 2 was a monocenter clinical
study including patients with AD (n = 32), mild cognitive impairment (n = 13),
other dementias (n = 15), as well as cognitively healthy controls (n = 20).
RESULTS: UCH-L1 and P-tau231 were elevated in AD patients compared to controls in
both cohorts. CSF levels of DJ-1 and NSE were unchanged in the AD group, whereas
they were decreased in the group of other dementia compared to controls in the
clinical study. CONCLUSION: Our main findings support that the UPS pathway may be
impaired in AD, and UCH-L1 may serve as an additional CSF biomarker for AD.
PMID- 27504118
TI - Low Leptin Availability as a Risk Factor for Dementia in Chilean Older People.
AB - OBJECTIVE: The aim was to study the role of leptin in the development of
dementia. METHODS: Follow-up of the ALEXANDROS cohorts, with baseline
measurements in 2000. From 1,136 available subjects free of dementia at baseline,
667 subjects had frozen baseline blood samples for measuring leptin and soluble
leptin receptor (sOB-R). The free leptin index (FLI) was calculated as the ratio
of leptin to sOB-R. Dementia was defined as an MMSE score <22 and a score >5 in
the Pfeffer Activities Questionnaire. RESULTS: After 15 years of follow-up, 42
incident cases of dementia were identified. No difference in serum leptin was
observed between people with and without dementia, but sOB-R was higher in
demented than in nondemented subjects (sOB-R: 44.94 +/- 23.97 vs. 33.73 +/- 21.13
ng/ml). The adjusted risk for dementia increased, the higher the log sOB (hazard
ratio = 3.58; 95% CI 1.72-7.45, p = 0.001). CONCLUSION: Lower availability of
free leptin was found in demented than in nondemented people, suggesting a role
of leptin in cognition.
PMID- 27504119
TI - Low Cerebrospinal Fluid Amyloid-Beta Concentration Is Associated with Poorer
Delayed Memory Recall in Women.
AB - BACKGROUND: Data on the association of memory performance with cerebrospinal
fluid (CSF) biomarkers of Alzheimer's disease (AD) are inconsistent. The
Consortium to Establish a Registry for Alzheimer's Disease neuropsychological
battery (CERAD-NB) is a commonly used validated cognitive tool; however, only few
studies have examined its relationship with CSF biomarkers for AD. We studied the
correlation of pathological changes in CSF biomarkers with various CERAD-NB
subtests and total scores. METHODS: Out of 79 subjects (36 men, mean age 70.5
years), 63 had undergone an assessment of cognitive status with CERAD-NB and a
CSF biomarker analysis due to a suspected memory disorder, and 16 were controls
with no memory complaint. RESULTS: In women we found a significant correlation
between CSF amyloid-beta (Abeta1-42) and several subtests measuring delayed
recall. Word List Recall correlated with all markers: Abeta1-42 (r = 0.323, p =
0.035), tau (r = -0.304, p = 0.050) and hyperphosphorylated tau (r = -0.331, p =
0.046). No such correlations were found in men. CONCLUSIONS: CSF biomarkers
correlate with delayed memory scores in CERAD-NB in women, and women may have
more actual AD pathology at the time of the investigations than men.
PMID- 27504120
TI - Profile of the Spleen Transcriptome in Beef Steers with Variation in Gain and
Feed Intake.
AB - We have previously identified components of the immune system contributing to
feed intake and gain in both the rumen and small intestine of beef steers. In
this study, we examined the spleen, a major lymphatic organ near the digestive
tract, to determine whether it was also influencing individual feed efficiency
status through immune responses. Animals (n = 16) that were divergent for gain
and intake were selected for tissue sampling. The spleen transcriptomes were
evaluated by microarray. A total of 1216 genes were identified as differentially
expressed. Genes were over-represented in Kyoto encyclopedia of genes and genomes
(KEGG) pathways including biological regulation, protein folding, cell
communication, immune systems process, response to stress, and RNA metabolic
process. Several stress response or heat shock genes including HSPH1, HSPA1A,
HSPA4, DNAJB4, DNAJA4, etc., were identified as a stress response functional gene
cluster in the low gain-low intake animals. These genes were up-regulated amongst
the low gain-low intake animals compared to all other groups. Canonical pathways
associated with the differentially expressed genes included the coagulation
system, extrinsic prothrombin activation, protein ubiquitination, unfolded
protein response, and aldosterone signaling in epithelial cells. An analysis of
expressed copy number variable (CNV) genes in the spleen produced some of the
same genes and gene families that were differentially expressed. Our data
suggests the splenic contribution to some of the underlying variation among gain
and intake within this group of animals may be a result of immune function and
stress response. In addition, some of the differences in immune response
functions may be related to gene copy number.
PMID- 27504121
TI - Ulcerative Colitis Activity Presenting as Fever of Unknown Origin, in a Patient
with Longstanding Disease under Continuous Treatment with Mesalazine.
AB - Background. The presence of ulcerative colitis (UC) with no bowel symptoms, as
fever of unknown origin (FUO), is uncommon. Objective. To describe the case of an
80-year-old woman who presented with fever, with a history of UC under treatment
with mesalazine. Case Presentation. She was admitted due to fever lasting for 12
days with no associated symptoms. Seven years earlier, she was diagnosed with UC.
After an extended workup for FUO that failed to reach the diagnosis, she
underwent a gallium-67 scintigraphy. This revealed a persistent diffuse
concentration of gallium-67 in the ascending colon at 24-hour imaging that
remained stable at 48- and 72-hour imaging without any topographic change after
the use of laxatives. Considering the results and in the absence of another
diagnosis, the patient was treated with 30 mg prednisone daily and mesalazine, as
treatment of active UC. Subsequently, the patient's condition improved markedly
and the fever retreated. One month later, she was reevaluated with a gallium-67
scintigraphy with total absence of gallium-67 concentration in the ascending
colon. Conclusion. UC activity must be included in the differential diagnosis of
FUO in patients with longstanding disease, since fever may present alone, with no
other manifestations.
PMID- 27504122
TI - Diversification of Antitumour Immunity in a Patient with Metastatic Melanoma
Treated with Ipilimumab and an IDO-Silenced Dendritic Cell Vaccine.
AB - Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) inhibits T
cell activation and promotes T-cell differentiation into regulatory T-cells.
Moreover, IDO expression promotes resistance to immunotherapies targeting immune
checkpoints such as the cytotoxic T lymphocyte antigen-4 (CTLA-4). Here, a
patient with metastatic melanoma pretreated with ipilimumab, an anti-CTLA-4
blocking antibody, was vaccinated with IDO-silenced DCs cotransfected with mRNA
for survivin or hTERT tumour antigens. During vaccination, T-cell responses to
survivin and hTERT tumour antigens were generated, and a certain degree of
clinical benefit was achieved, with a significant reduction in lung, liver, and
skin metastases, along with a better performance status. T-cell responses against
MART-1 and NY-ESO-1 tumour antigens were also detected in the peripheral blood.
The patient also mounted an antibody response to several melanoma proteins,
indicating diversification of the antitumour immunity in this patient. The
identification of such serum antibody-reacting proteins could facilitate the
discovery of tumour neoantigens.
PMID- 27504123
TI - Mystixin-7 Peptide Protects Ionotropic Glutamatergic Mechanisms against Glutamate
Induced Excitotoxicity In Vitro.
AB - Hyperactivation of the N-methyl-D-aspartic acid type glutamate receptors (NMDARs)
causes glutamate excitotoxicity, a process potentially important for many
neurological diseases. This study aims to investigate protective effects of the
synthetic corticotrophin-releasing factor-like peptide, mystixin-7 (MTX), on
model glutamate-induced excitotoxicity in vitro. The technique online monitoring
of electrophysiological parameters (excitatory glutamatergic alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionic (AMPAR) and NMDAR-dependent postsynaptic
mechanisms) in the olfactory cortex slices was used. Application of L-glutamate
in toxic concentration (20 mM) on slices evoked hyperactivation of NMDARs and
weaker activation of the AMPARs. Upon further action agonist, the excessive
activation of glutamate receptors was replaced by their irreversible blockade.
Pretreatment of the slices using MTX in different concentrations (50 and 100
mg/mL) protected both NMDARs and AMPARs from glutamate-induced damage. An
enzymatic treatment of MTX reduced hyperactivation of both NMDARs and AMPARs. The
present study demonstrated that MTX minipeptide protected the functioning of both
NMDARs and AMPARs against glutamate-induced damage. The MTX peptide is a
prospective candidate for elaborated medication in treatment of neurological
diseases.
PMID- 27504124
TI - Focal partial salvage low-dose-rate brachytherapy for local recurrent prostate
cancer after permanent prostate brachytherapy with a review of the literature.
AB - PURPOSE: To investigate the treatment results for focal partial salvage re
implantation against local recurrence after permanent prostate brachytherapy.
MATERIAL AND METHODS: Between January 2010 and September 2015, 12 patients were
treated with focal partial salvage re-implantation for local recurrence after low
dose-rate brachytherapy using (125)I seeds. The focal clinical target volume (F
CTV) was delineated on positive biopsy areas in a mapping biopsy, combining the
cold spots on the post-implant dosimetry for initial brachytherapy. The F-CTV was
expanded by 3 mm to create the planning target volume (PTV) as a margin to
compensate for uncertainties in image registration and treatment delivery. The
prescribed dose to the PTV was 145 Gy. The characteristics and biochemical
disease-free survival (BdFS) rates were analyzed. Genitourinary (GU) and
gastrointestinal (GI) toxicities were evaluated using the Common Terminology
Criteria for Adverse Events version 4. RESULTS: The median prostate-specific
antigen (PSA) level at re-implantation was 4.09 ng/ml (range: 2.91-8.24 ng/ml).
The median follow-up time was 56 months (range: 6-74 months). The median RD2cc
and UD10 were 63 Gy and 159 Gy, respectively. The 4-year BdFS rate was 78%, which
included non-responders. Biochemical recurrence occurred in two patients after 7
and 31 months, respectively. The former was treated with hormonal therapy after
biochemical failure, and the latter underwent watchful waiting (PSA at the last
follow-up of 53 months: 7.3 ng/ml) at the patient's request. No patients had
grade 3 GU/GI toxicities or died after salvage re-implantation. CONCLUSIONS: The
partial salvage low-dose-rate brachytherapy used to treat local recurrence after
permanent prostate brachytherapy is well-tolerated, with high biochemical
response rates. This treatment can be not only a method to delay chemical
castration but also a curative treatment option in cases of local recurrence of
prostate carcinoma after seed implantation.
PMID- 27504125
TI - Institutional experience using interstitial brachytherapy for the treatment of
primary and recurrent pelvic malignancies.
AB - PURPOSE: The study assessed the outcomes of patients at a single institution with
locally advanced primary and recurrent pelvic malignancies treated with
interstitial high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy (BT),
using a modified Syed-Neblett template. MATERIAL AND METHODS: Between 1996 and
2010, 60 patients with primary or recurrent pelvic malignancies were treated with
interstitial BT. Thirty three patients had primary malignancies with 6.1% being
stage I, 33.3% stage II, 45.5% stage III, and 15.2% stage IV; the remaining 27
patients were recurrent malignancies. Fifty four patients received external beam
radiotherapy (EBRT) as part of their treatment course. The median EBRT, BT, and
EBRT + BT doses were 45 Gy, 20 Gy, and 65 Gy, respectively. Thirty eight patients
received concurrent chemotherapy with EBRT. Complete response (CR) was defined by
absence of clinical and radiographic disease on first follow-up. Toxicity was
graded as per Common Terminology Criteria for Adverse Events, version 4.0.
RESULTS: The median follow-up was 37 months (4-234 months) and initial CR was
achieved in 91%. For primary cancers at diagnosis, 5-year local control (LC), 5
year progression-free survival (PFS), 5-year overall survival (OS) were 65%, 64%,
and 42% respectively. For recurrent cancers at diagnosis, 5-year LC, 5-year PFS,
and 5-year OS were 80%, 51%, and 37%, respectively. There was a significant
difference in both OS and PFS among different tumor sites (p < 0.05), with
vaginal cancers having the best 5-year OS (55%) and PFS (84%). There was a total
of 1 acute toxicity >= grade 3, 6 late grade 3 toxicities, and late grade 4
toxicity. CONCLUSIONS: Our series suggests that interstitial BT using a modified
Syed-Neblett template is a safe and effective treatment for primary or recurrent
pelvic malignancies. This technique allowed effective LC and 97% of patients had
preservation of both bladder and rectal function.
PMID- 27504126
TI - Predictive criteria for MRI-based evaluation of response both during and after
radiotherapy for cervical cancer.
AB - PURPOSE: For cervical carcinoma, the presence of persistent disease after
radiotherapy (RT) is a significant predictor for survival. To date, no standard
protocol is available to evaluate a response. This study was performed to assess
magnetic resonance imaging (MRI) to evaluate presence of local residual disease
during and after RT for Federation of Gynecology and Obstetrics (FIGO) stage Ib1
IVa cervical cancer. MATERIAL AND METHODS: Forty-two patients were included.
Patients underwent MRI before external beam RT, at final intracavitary
brachytherapy (BCT) and 2-3 months after completion of RT. Two blinded
radiologists (observer 1: experienced, observer 2: less experienced) scored the
likelihood of residual tumor. Magnetic resonance imaging was evaluated by means
of (a) 'subjective' visual evaluation of T2 weighted MRI images, and (b)
'objective' visual evaluation of T2 weighted MRI images according to predefined
imaging criteria. RESULTS: Seven patients had residual disease. Area under the
receiver operating characteristics curve (AUC) for 'subjective' visual assessment
was 0.79/0.75 (observer 1/observer 2) after RT and 0.75/0.43 at final BCT. The
combined 'objective' MRI criteria (isointense, nodular, and irregular) resulted
in improved prediction of residual tumor (AUCs of 0.91/0.85 after RT). For the
less experienced observer, the MRI criteria set significantly improved prediction
of residual tumor compared to 'subjective' visual assessment. Observer dependency
decreased, kappa of 0.41 compared to 0.84 for the MRI criteria set after RT.
CONCLUSION: Compared to 'subjective' visual assessment, predefined 'objective'
MRI criteria increase diagnostic performance and decrease observer dependency for
assessing residual tumor after RT in cervical cancer.
PMID- 27504127
TI - Clinical comparison of brachytherapy versus hypofractionated external beam
radiation versus standard fractionation external beam radiation for non
melanomatous skin cancers.
AB - PURPOSE: Non-melanomatous skin cancer (NMSC) is the single most common cancer in
the US. Radiation therapy is an excellent treatment alternative to surgery. High
dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) are commonly
used radiation treatment modalities but little data is published comparing these
modalities. We present our institution's experience and outcomes with these
therapeutic options. MATERIAL AND METHODS: From June 2005 to March 2013, 61
patients were treated with HDR brachytherapy (n = 9), hypofractionated EBRT (n =
30), or standard fractionation EBRT (n = 22) for NMSC. The primary outcome
measure was local control at most remote follow-up and secondary outcome measures
were overall survival, cosmetic outcome, and toxicity. Univariate analysis was
performed to compare outcomes between treatment modalities. Kaplan-Meier analysis
and log-rank test were used to compare overall survival. RESULTS: Median follow
up was 30 months. The most common histologies were BCC (47%) and SCC (44%); mean
patient age was 83.3 years. Local control was 81% and 2-year actuarial overall
survival was 89%. There was no statistical difference in local control or overall
survival between treatment modalities. There was no statistical difference in
cosmetic outcome or toxicity between treatment modalities, although five of six
"poor" cosmetic outcomes and the only grade 3 toxic events were found in the
standard fractionation EBRT group. CONCLUSIONS: All modalities investigated
represent effective treatments for NMSC and have good cosmetic outcomes and
acceptable toxicity profiles. The finding of higher grade toxicity and a greater
portion of patients experiencing toxicity among standard fractionation therapy is
counter to expectations. There was no statistical significance to the finding and
it is not likely to be meaningful.
PMID- 27504128
TI - Highly conformal CT based surface mould brachytherapy for non-melanoma skin
cancers of earlobe and nose.
AB - PURPOSE: Brachytherapy (BT), due to rapid dose fall off and minor set-up errors,
should be superior to external beam radiotherapy (EBRT) for treatment of lesions
in difficult locations like nose and earlobe. Evidences in this field are scarce.
We describe computed tomography (CT) based surface mould BT for non-melanoma skin
cancers (NMSC), and compare its conformity, dose coverage, and tissue sparing
ability to EBRT. MATERIAL AND METHODS: We describe procedure of preparation of
surface mould applicator and dosimetry parameters of BT plans, which were
implemented in 10 individuals with NMSC of nose and earlobe. We evaluated dose
coverage by minimal dose to 90% of planning target volume (PTV) (D90), volumes of
PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for
90 and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose
nonuniformity ratio (DNR), exposure of organs. Prospectively, we created CT-based
photons and electrons plans. We compared conformity (COIN90, COIN100), dose
coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD
(V10-V90) of EBRT and BT plans. RESULTS: We obtained mean BT-DHI = 0.76, BT-DNR =
0.23, EBRT-DHI = 1.26. We observed no significant differences in VPTV90 and D90
between BT and EBRT. Mean BT-VPTV100 (89.4%) was higher than EBRT-VPTV100
(71.2%). Both COIN90 (BT-COIN90 = 0.46 vs. EBRT-COIN90 = 0.21) and COIN100 (BT
COIN100 = 0.52 vs. EBRT-COIN100 = 0.26) were superior for BT plans. We observed
more exposure of normal tissues for small doses in BT plans (V10, V20), for high
doses in EBRT plans (V70, V90). CONCLUSIONS: Computed tmography-based surface
mould brachytherapy for superficial lesions on irregular surfaces is a highly
conformal method with good homogeneity. Brachytherapy is superior to EBRT in
those locations in terms of conformity and normal tissue sparing ability in high
doses.
PMID- 27504129
TI - Robustness of IPSA optimized high-dose-rate prostate brachytherapy treatment
plans to catheter displacements.
AB - PURPOSE: Inverse planning simulated annealing (IPSA) optimized brachytherapy
treatment plans are characterized with large isolated dwell times at the first or
last dwell position of each catheter. The potential of catheter shifts relative
to the target and organs at risk in these plans may lead to a more significant
change in delivered dose to the volumes of interest relative to plans with more
uniform dwell times. MATERIAL AND METHODS: This study aims to determine if the
Nucletron Oncentra dwell time deviation constraint (DTDC) parameter can be
optimized to improve the robustness of high-dose-rate (HDR) prostate
brachytherapy plans to catheter displacements. A set of 10 clinically acceptable
prostate plans were re-optimized with a DTDC parameter of 0 and 0.4. For each
plan, catheter displacements of 3, 7, and 14 mm were retrospectively applied and
the change in dose volume histogram (DVH) indices and conformity indices
analyzed. RESULTS: The robustness of clinically acceptable prostate plans to
catheter displacements in the caudal direction was found to be dependent on the
DTDC parameter. A DTDC value of 0 improves the robustness of planning target
volume (PTV) coverage to catheter displacements, whereas a DTDC value of 0.4
improves the robustness of the plans to changes in hotspots. CONCLUSIONS: The
results indicate that if used in conjunction with a pre-treatment catheter
displacement correction protocol and a tolerance of 3 mm, a DTDC value of 0.4 may
produce clinically superior plans. However, the effect of the DTDC parameter in
plan robustness was not observed to be as strong as initially suspected.
PMID- 27504130
TI - Clinical applications of custom-made vaginal cylinders constructed using three
dimensional printing technology.
AB - PURPOSE: Three-dimensional (3D) printing technology allows physicians to rapidly
create customized devices for patients. We report our initial clinical experience
using this technology to create custom applicators for vaginal brachytherapy.
MATERIAL AND METHODS: Three brachytherapy patients with unique clinical needs
were identified as likely to benefit from a customized vaginal applicator.
Patient 1 underwent intracavitary vaginal cuff brachytherapy after hysterectomy
and chemotherapy for stage IA papillary serous endometrial cancer using a custom
printed 2.75 cm diameter segmented vaginal cylinder with a central channel.
Patient 2 underwent interstitial brachytherapy for a vaginal cuff recurrence of
endometrial cancer after prior hysterectomy, whole pelvis radiotherapy, and
brachytherapy boost. We printed a 2 cm diameter vaginal cylinder with one central
and six peripheral catheter channels to fit a narrow vaginal canal. Patient 3
underwent interstitial brachytherapy boost for stage IIIA vulvar cancer with
vaginal extension. For more secure applicator fit within a wide vaginal canal, we
printed a 3.5 cm diameter solid cylinder with one central tandem channel and ten
peripheral catheter channels. The applicators were printed in a biocompatible,
sterilizable thermoplastic. RESULTS: Patient 1 received 31.5 Gy to the surface in
three fractions over two weeks. Patient 2 received 36 Gy to the CTV in six
fractions over two implants one week apart, with interstitial hyperthermia once
per implant. Patient 3 received 18 Gy in three fractions over one implant after
45 Gy external beam radiotherapy. Brachytherapy was tolerated well with no grade
3 or higher toxicity and no local recurrences. CONCLUSIONS: We established a
workflow to rapidly manufacture and implement customized vaginal applicators that
can be sterilized and are made of biocompatible material, resulting in high
quality brachytherapy for patients whose anatomy is not ideally suited for
standard, commercially available applicators.
PMID- 27504131
TI - Potential role of TRAns Cervical Endosonography (TRACE) in brachytherapy of
cervical cancer: proof of concept.
AB - PURPOSE: Magnetic resonance imaging (MRI) is the gold standard for image guided
adaptive brachytherapy (BT) of cervical cancer. Ultrasound is an attractive
alternative with reasonable costs and high soft tissue depiction quality. This
technical note aims to demonstrate the proof of principle for use of TRAns
Cervical Endosonography with rotating transducer in the context of brachytherapy
(TRACE BT). MATERIAL AND METHODS: TRACE BT presentation is based on a single
stage IIB cervical cancer patient. Prior to second BT implant, rotating US
transducer (6.9 mm diameter) was inserted in cervical canal and axial images
obtained at 10 MHz, focal range of 30 mm, and axial resolution of 0.4 mm. Size
and topography of hypo-echoic areas were assessed and optimal positions of
interstitial needles were determined. Finally, intracavitary applicator was
placed and needles inserted through vaginal ring-template according to TRACE pre
plan. MRI-based high risk clinical target volume (CTVHR) dimensions were compared
with hypoechoic areas on TRACE. Topography of parametrial needles on post
insertion MRI was compared with TRACE pre-plan. RESULTS: Insertion of rotating
mechanism into cervico-uterine cavity was safe, feasible and fast. The 360
degrees imaging in axial plane enabled real-time assessment of cervix, uterus,
and adjacent parametria. Qualitative comparison of TRACE with post-insertion MRI
revealed favorable agreement of findings. In-plane size of CTVHR on MRI was
comparable to hypoechoic areas on TRACE. Needle positions on post-insertion MRI
corresponded to TRACE-based pre-plan. Main limitation of TRACE was gradual
deterioration of image quality due to coupling gel removal. CONCLUSIONS: Present
proof of concept demonstrates potential role of TRACE-BT for cervical cancer as
an attractive high-tech approach with reasonable costs. Prior to investigation of
its clinical role, further development of TRACE methodology is needed. This
includes reliable transducer-tissue coupling, applicator reconstruction, imaging
range, limitations in extensive tumors, US-based contouring concepts,
registration with other imaging methods, organ dose-assessment, real-time
dosimetry, etc.
PMID- 27504132
TI - Dosimetric study for cervix carcinoma treatment using intensity modulated
radiation therapy (IMRT) compensation based on 3D intracavitary brachytherapy
technique.
AB - PURPOSE: Intensity modulated radiation therapy (IMRT) compensation based on 3D
high-dose-rate (HDR) intracavitary brachytherapy (ICBT) boost technique (ICBT +
IMRT) has been used in our hospital for advanced cervix carcinoma patients. The
purpose of this study was to compare the dosimetric results of the four different
boost techniques (the conventional 2D HDR intracavitary brachytherapy [CICBT], 3D
optimized HDR intracavitary brachytherapy [OICBT], and IMRT-alone with the
applicator in situ). MATERIAL AND METHODS: For 30 patients with locally advanced
cervical carcinoma, after the completion of external beam radiotherapy (EBRT) for
whole pelvic irradiation 45 Gy/25 fractions, five fractions of ICBT + IMRT boost
with 6 Gy/fractions for high risk clinical target volume (HRCTV), and 5
Gy/fractions for intermediate risk clinical target volume (IRCTV) were applied.
Computed tomography (CT) and magnetic resonance imaging (MRI) scans were acquired
using an in situ CT/MRI-compatible applicator. The gross tumor volume (GTV), the
high/intermediate-risk clinical target volume (HRCTV/IRCTV), bladder, rectum, and
sigmoid were contoured by CT scans. RESULTS: For ICBT + IMRT plan, values of D90,
D100 of HRCTV, D90, D100, and V100 of IRCTV significantly increased (p < 0.05) in
comparison to OICBT and CICBT. The D2cc values for bladder, rectum, and sigmoid
were significantly lower than that of CICBT and IMRT alone. In all patients, the
mean rectum V60 Gy values generated from ICBT + IMRT and OICBT techniques were
very similar but for bladder and sigmoid, the V60 Gy values generated from ICBT +
IMRT were higher than that of OICBT. For the ICBT + IMRT plan, the standard
deviations (SD) of D90 and D2cc were found to be lower than other three treatment
plans. CONCLUSIONS: The ICBT + IMRT technique not only provides good target
coverage but also maintains low doses (D2cc) to the OAR. ICBT + IMRT is an
optional technique to boost parametrial region or tumor of large size and
irregular shape when intracavitary/interstitial brachytherapy cannot be used.
PMID- 27504133
TI - Development of a magnetic resonance imaging protocol to visualize encapsulated
contrast agent markers in prostate brachytherapy recipients: initial patient
experience.
AB - PURPOSE: Computed tomography (CT)-based prostate post-implant dosimetry allows
for definitive seed localization but is associated with high interobserver
variation in prostate contouring. Currently, magnetic resonance imaging (MRI)
based post-implant dosimetry allows for accurate anatomical delineation but is
limited due to inconsistent seed localization. Encapsulated contrast agent
markers were previously proposed to overcome the seed localization limitation on
MRI images by placing hyperintense markers adjacent to hypointense seeds. The aim
of this study was to assess the appearance of these markers in prostatic tissue,
and develop an MRI protocol to enable marker visualization. MATERIAL AND METHODS:
We acquired MRI scans in prostate implant patients (n = 10) on day 0 (day of
implant) and day 30 (month after implant). Before implantation of the markers,
the routine post-implant MRI protocol included a 3D T2-weighted fast-spin-echo
(FSE) sequence with which markers and seeds could not be clearly visualized. To
visualize the MRI markers, a 3D fast radiofrequency-spoiled gradient-recalled
echo (FSPGR) sequence was evaluated for marker and seed visibility, as well as
prostate boundary definitions. RESULTS: The 3D FSPGR sequence allowed for the
visualization of markers in the prostate, enabling the distinction of signal
voids as seeds versus needle tracks. The updated post-implant MRI protocol
consists of this 3D FSPGR scan and an optional 3D T2-weighted FSE scan. The
optional 3D T2-weighted FSE sequence may be employed to better visualize
intraprostatic detail. We also described the observed image artifacts, including
seed susceptibility, marker chemical shift, partial volume averaging, motion, and
wraparound artifacts. CONCLUSIONS: We have demonstrated an MRI protocol for use
with hyperintense encapsulated contrast agent markers to assist in the
identification of hypointense seeds.
PMID- 27504134
TI - Single fraction multimodal image guided focal salvage high-dose-rate
brachytherapy for recurrent prostate cancer.
AB - PURPOSE: We present a novel method for treatment of locally recurrent prostate
cancer (PCa) following radiation therapy: focal, multimodal image guided high
dose-rate (HDR) brachytherapy. MATERIAL AND METHODS: We treated two patients with
recurrent PCa after primary (#1) or adjuvant (#2) external beam radiation
therapy. Multiparametric magnetic resonance imaging (mpMRI), choline, positron
emission tomography combined with computed tomography (PET/CT), or prostate
specific membrane antigen (PSMA)-PET combined with CT identified a single
intraprostatic lesion. Positron emission tomography or magnetic resonance imaging
- transrectal ultrasound (MRI-TRUS) fusion guided transperineal biopsy confirmed
PCa within each target lesion. We defined a PET and mpMRI based gross tumor
volume (GTV). A 5 mm isotropic margin was applied additionally to each lesion to
generate a planning target volume (PTV), which accounts for technical fusion
inaccuracies. A D90 of 18 Gy was intended in one fraction to each PTV using
ultrasound guided HDR brachytherapy. RESULTS: Six month follow-up showed adequate
prostate specific antygen (PSA) decline in both patients (DeltaPSA 83% in patient
1 and DeltaPSA 59.3% in patient 2). Follow-up 3-tesla MRI revealed regressive
disease in both patients and PSMA-PET/CT showed no evidence of active disease in
patient #1. No acute or late toxicities occurred. CONCLUSIONS: Single fraction,
focal, multimodal image guided salvage HDR brachytherapy for recurrent prostate
cancer is a feasible therapy for selected patients with single lesions. This
approach has to be evaluated in larger clinical trials.
PMID- 27504135
TI - Image-guided high-dose-rate brachytherapy of malignancies in various inner organs
- technique, indications, and perspectives.
AB - In the last few years, minimally invasive tumor ablation performed by
interventional radiologists has gained increasing relevance in oncologic patient
care. Limitations of thermal ablation techniques such as radiofrequency ablation
(RFA), microwave ablation (MWA), and laser-induced thermotherapy (LITT),
including large tumor size, cooling effects of adjacent vessels, and tumor
location near thermosensitive structures, have led to the development of image
guided high-dose-rate (HDR) brachytherapy, especially for the treatment of liver
malignancies. This article reviews technical properties of image-guided
brachytherapy, indications and its current clinical role in multimodal cancer
treatment. Furthermore, perspectives of this novel therapy option will be
discussed.
PMID- 27504136
TI - PGC-1alpha Mediated Peripheral Nerve Protection of Tongxinluo in STZ-Induced
Diabetic Rats.
AB - Aim. To investigate the effect of Tongxinluo (Txl), a Chinese herbal compound, on
diabetic peripheral neuropathy (DPN). Methods and Results. Diabetic rat model was
established by peritoneal injection of streptozotocin (STZ). Txl ultrafine powder
treatment for 16 weeks from the baseline significantly reversed the impairment of
motor nerve conductive velocity (MNCV), mechanical hyperalgesia, and nerve
structure. We further proved that Tongxinluo upregulates PGC-1alpha and its
downstream factors including COX IV and SOD, which were involved in mitochondrial
biogenesis. Conclusion. Our study indicates that the protective effect of Txl in
diabetic neuropathy may be attributed to the induction of PGC-1alpha and its
downstream targets. This finding may further illustrate the pleiotropic effect of
the medicine.
PMID- 27504137
TI - Inhibitory Effect of Yongdamsagan-Tang Water Extract, a Traditional Herbal
Formula, on Testosterone-Induced Benign Prostatic Hyperplasia in Rats.
AB - Yongdamsagan-tang, a traditional herbal formula, is used widely for the treatment
of inflammation and viral diseases. In this study, we investigated whether
Yongdamsagan-tang water extract (YSTE) affects testosterone propionate- (TP-)
induced benign prostatic hyperplasia (BPH) in a rat model. To induce BPH, rats
were injected subcutaneously with 10 mg/kg of TP every day. YSTE was
administrated daily by oral gavage at doses of 200 and 500 mg/kg along with the
TP injection. After 4 weeks, prostates were collected, weighed, and analyzed. The
relative prostrate weight was significantly lower in both YSTE groups (200 and
500 mg/kg/day) compared with the TP-induced BPH group. YSTE administration
reduced the expression of proliferation markers PCNA, cyclin D1, and Ki-67 and
the histological abnormalities observed in the prostate in TP-induced BPH rats.
YSTE attenuated the increase in the TP-induced androgen concentration in the
prostate. The YSTE groups also showed decreased lipid peroxidation and increased
glutathione reductase activity in the prostate. These findings suggest that YSTE
effectively prevented the development of TP-induced BPH in rats through
antiproliferative and antioxidative activities and might be useful in the
clinical treatment of BPH.
PMID- 27504138
TI - Pain and Inflammation: Update on Emerging Phytotherapy, Zootherapy, and
Nutritional Therapies.
PMID- 27504139
TI - Extracorporeal Shock Wave Stimulation as Alternative Treatment Modality for Wrist
and Fingers Spasticity in Poststroke Patients: A Prospective, Open-Label,
Preliminary Clinical Trial.
AB - Objective. To evaluate the effectiveness of radial shock waves (rESW) for wrist
and fingers flexors spasticity in stroke patients. Methods. Twenty patients with
upper limb muscle spasticity were enrolled in the study and treated with a single
session of rESW. The spasticity level of the radio carpal (RC) and finger (FF)
joints was assessed using Modified Ashworth Scale (MAS). The resting
bioelectrical activity of the flexor carpi radialis (FCR) and flexor carpi
ulnaris (FCU) was examined using surface electromyography (sEMG). Trophic
conditions were measured using infrared thermal (IRT) imaging. All measurements
were conducted at baseline (t 0), immediately after rESW (t 1), and 1 (t 2) and
24 (t 3) hours following rESW. Results. Significant reduction in MAS was observed
for the RC joint in t 1, as well as for the FF joints in t 1, t 2, and t 3. A
significant decrease in sEMG was shown for the FCR muscle in t 1 and t 2, as well
as for the FCU muscle in t 1 and t 3. Also, a significant increase in IRT value
was observed in t 3 only. Conclusions. A single session of rESW could be an
effective alternative treatment for reduction of limb spasticity and could lead
to improvement of trophic conditions of the spastic muscles.
PMID- 27504140
TI - MAPK Pathways Are Involved in Neuropathic Pain in Rats with Chronic Compression
of the Dorsal Root Ganglion.
AB - The aim of the present study was to investigate whether the MAPK pathways were
involved in the mechanism of neuropathic pain in rats with chronic compression of
the dorsal root ganglion. We determined the paw withdrawal mechanical threshold
(PWMT) of rats before and after CCD surgery and then after p38, JNK, or ERK
inhibitors administration. Western blotting, RT-PCR, and immunofluorescence of
dorsal root ganglia were performed to investigate the protein and mRNA level of
MAPKs and also the alternation in distributions of positive neurons in dorsal
root ganglia. Intrathecal administration of MAPKs inhibitors, SB203580 (p38
inhibitor), SP600125 (JNK inhibitor), and U0126 (ERK inhibitor), resulted in a
partial reduction in CCD-induced mechanical allodynia. The reduction of allodynia
was associated with significant depression in the level of both MAPKs mRNA and
protein expression in CCD rats and also associated with the decreased ratios of
large size MAPKs positive neurons in dorsal root ganglia. In conclusion, the
specific inhibitors of MAPKs contributed to the attenuation of mechanical
allodynia in CCD rats and the large size MAPKs positive neurons in dorsal root
ganglia were crucial.
PMID- 27504141
TI - System effectiveness of detection, brief intervention and refer to treatment for
the people with post-traumatic emotional distress by MERS: a case report of
community-based proactive intervention in South Korea.
AB - BACKGROUND: Korea has experienced diverse kind of disasters these days. Among
them the 2015 middle eastern respiratory syndrome (MERS) outbreak imposed great
psychological stress on almost all Korean citizens. Following the MERS outbreak,
government is reviewing overall infectious disease management system and
prioritizing the establishment of mental health service systems for infectious
disease. This study makes suggestions for implementing disaster-related mental
health service systems by analyzing the example of Gyeonggi Province, which
proactively intervened with residents' psychological problems caused by the large
scale outbreak of an infectious disease. CASE DESCRIPTION: Mental health service
system for MERS victims had the following two parts: a mental health service for
people who had been placed in quarantine and a service provided to families of
patients who had died or recovered patients. The government of Gyeonggi province,
public health centers, regional and local Community Mental Health Centers and the
National Center for Crisis Mental Health Management participated in this service
system. Among 1221 Gyeonggi people placed in quarantine and who experienced
psychological and emotional difficulties, 350 required continuing services; 124
of this group received continuing services. That is, 35 % of people who required
psychological intervention received contact from service providers and received
the required services. CONCLUSIONS: This study reflects a proactive monitoring
system for thousands of people placed under quarantine for the first time in
Korea. It is significant that the service utilization rate by a proactive manner,
that is the professionals administering it actively approached and contacted
people with problems rather than passively providing information was much higher
than other general mental health situation in Korea. The core value of public
mental health services is adequate public accessibility; it is therefore
essential for governments to strengthen their professional competence and
establish effective systems. These criteria should also be applied to
psychological problems caused by disastrous infectious disease outbreaks.
PMID- 27504142
TI - Thoughts about SLC16A2, TSIX and XIST gene like sites in the human genome and a
potential role in cellular chromosome counting.
AB - BACKGROUND: Chromosome counting is a process in which cells determine somehow
their intrinsic chromosome number(s). The best-studied cellular mechanism that
involves chromosome counting is 'chromosome-kissing' and X-chromosome
inactivation (XCI) mechanism. It is necessary for the well-known dosage
compensation between the genders in mammals to balance the number of active X
chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI,
two X-chromosomes are coming in close proximity and pair physically by a specific
segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene.
RESULTS: An Ensembl BLAST search for human and mouse SLC16A2/Slc16a2 homologues
revealed, that highly similar sequences can be found at almost each chromosome in
the corresponding genomes. Additionally, a BLAST search for SLC16A2/TSIX/XIST
(genes responsible for XCI) reveled that "SLC16A2/TSIX/XIST like sequences" cover
equally all chromosomes, too. With respect to this we provide following
hypotheses. HYPOTHESES: If a single genomic region containing the SLC16A2 gene on
X-chromosome is responsible for maintaining "balanced" active copy numbers, it is
possible that similar sequences or gene/s have the same function on other
chromosomes (autosomes). SLC16A2 like sequences on autosomes could encompass
evolutionary older, but functionally active key regions for chromosome counting
in early embryogenesis. Also SLC16A2 like sequence on autosomes could be involved
in inappropriate chromosomes pairing and, thereby be involved in aneuploidy
formation during embryogenesis and cancer development. Also, "SLC16A2/TSIX/XIST
gene like sequence combinations" covering the whole genome, could be important
for the determination of X:autosome ratio in cells and chromosome counting.
CONCLUSIONS: SLC16A2 and/or SLC16A2/TSIX/XIST like sequence dispersed across
autosomes and X-chromosome(s) could serve as bases for a counting mechanism to
determine X:autosome ratio and could potentially be a mechanism by which a cell
also counts its autosomes. It could also be that such specific genomic regions
have the same function for each specific autosome. As errors during the obviously
existing process of chromosome counting are one if not the major origin of
germline/somatic aneuploidy the here presented hypotheses should further
elaborated and experimentally tested.
PMID- 27504143
TI - Neurophysiological hyperresponsivity to sensory input in autism spectrum
disorders.
AB - BACKGROUND: Atypical sensory processing is a common clinical observation in
autism spectrum disorder (ASD). Neural hyperexcitability has been suggested as
the cause for sensory hypersensitivity, a frequently reported clinical
observation in ASD. We examined visual evoked responses to parametric increases
in stimulus contrast in order to model neural responsivity of sensory systems in
ASD. METHODS: Thirteen high-functioning individuals with ASD and 12 typically
developing (TD) individuals completed a steady-state visual evoked potential
study. Stimuli were vertical circular gratings oscillating at 3.76 Hz at varying
contrasts (5, 10, 20,..., 90 % contrast, 10 levels). The average spectral power
at the stimulus oscillation frequency was calculated for each contrast level.
RESULTS: The magnitude of evoked sensory responses increased at a significantly
greater rate and resulted in disproportionately elevated activation with higher
contrasts in the ASD group. Approximately 45 % of ASD participants had rates of
response increases greater than any TD participant. This alteration was highly
associated with parental reports of these participants' sensory difficulties.
CONCLUSIONS: Greater increases in visual responses over contrast manipulation
suggest heightened excitability in the sensory cortex in ASD participants.
Heightened neural excitability was observed in a substantial portion but not all
of the ASD participants. This pattern suggests that individuals with higher
excitability may constitute a neurobiologically distinct subgroup requiring
individualized treatment interventions.
PMID- 27504144
TI - Imaging of Retrosternal Space Lesions - A Pictorial Review.
AB - The retrosternal region (RSS) can be involved by diverse lesions. The RSS is the
region behind the sternum and anterior to the ascending aorta. It normally is
less than 3 cm deep. Chest X-ray is usually the first imaging modality to raise a
suspicion of RSS pathology; however computed tomography is the mainstay to
delineate and characterize lesions in this location. Lesions in this location
include thyroid, thymic and lymph node lesions; germ cell tumors and vascular
lesions. Lesions arising from the sternum, lungs as well as the pleura can also
involve this space. The pictorial review depicts the diverse spectrum of lesions
in this location.
PMID- 27504145
TI - Evaluation of the Course of the Inferior Alveolar Canal: The First CBCT Study in
an Iranian Population.
AB - BACKROUND: The frequent anatomical variations of the inferior alveolar nerve
(IAN) course should be considered prior to any treatment in this area. The aim of
this study was to evaluate the course of the inferior alveolar canal (IAC) as it
appears in the archived CBCT images of the mandible. MATERIAL/METHOD: This cross-
sectional study evaluated a sample of 156 CBCT examinations. The pattern of the
IAC was evaluated and the prevalence of different patterns according to age and
gender were recorded. In order to find the frequency of mandibular canal type
among different ages, the patients were put into the three age groups (20-29, 30
44 and 45-59).The data were analyzed using Chi-square test and the significance
level was set as p<=.05. RESULTS: Out of 156 patients, 52 canals was straight
type, 52 had Catenary type and 52 of them were presented with Progressive
descending type. There was not statistically significant difference between two
genders (Pv=0.092). According to the type of the IAC course, there was a not
statistically significant difference between the three age groups (Pv=0.32).
CONCLUSIONS: Cone beam computed tomography is a useful method for precise
assessment of the IAC course.
PMID- 27504146
TI - Intranodal Palisaded Myofibroblastoma: Radiological and Cytological Overview.
AB - BACKGROUND: Intranodal palisaded myofibroblastoma is a benign and very rare
mesenchymal neoplasm of the lymph nodes originating from differentiated smooth
muscle cells and myofibroblasts. CASE REPORT: We report a case of intranodal
palisaded myofibroblastoma in an 84-year-old woman with Parkinson's disease that
presented as a left inguinal mass. The diagnosis was made using ultrasound-guided
fine needle aspiration biopsy and consequent cytopathological examination that
included immunohistochemical analysis. Herein, we discuss the presentation of a
rare intranodal palisaded myofibroblastoma with emphasis on its ultrasonographic
and cytopathologic features. CONCLUSIONS: Intranodal palisaded myofibroblastoma
should be considered in the differential diagnosis of inguinal lymphadenopathy
and the diagnosis is possible with cytopathologic exam and immunohistochemical
analysis using ultrasound-guided FNA biopsy, guiding the clinician to nodal
excision rather than aggressive measures.
PMID- 27504147
TI - Assessing worldwide research activity on probiotics in pediatrics using Scopus
database: 1994-2014.
AB - BACKGROUND: A wide variety of probiotic products has been introduced into the
market in the past decade. Research trends and activity on probiotics help
understand how these products were evolved and their potential future role in
medicine. The objective of this study was to assess the research activity on
probiotics in pediatrics using bibliometric indicators and network visualization.
METHODS: Original and review articles on probiotics in pediatrics published
worldwide were retrieved from SciVerse, Scopus (1994-2014) and analyzed.
VOSviewer was used for network visualization. RESULTS: The total number of
documents published on probiotics in pediatrics was 2817. Research activity on
probiotics in pediatrics showed approximately 90- fold increase during the study
period. Approximately 22 % of published articles originated from USA and has the
greatest share, however, Finland ranked first when data were stratified by
population or income. The most productive institution in this field was Turku
University in Finland with 82 (2.91 %) articles. Half of the prolific authors
were also from Finland. Most of the published research activity appeared in
Journal of Pediatric Gastroenterology and Nutrition. Most frequently encountered
title terms include nutrition, infant formula, necrotizing enetrocolitis,
allergy, and diarrhea. The total number of citations for the retreived documents
documents was 70991, and the average citation per article was 25.20. CONCLUSIONS:
Interest in probiotic research and its potential benefits in pediatric ailments
is relatively recent but significantly increasing. Bibliometric analysis can be
used as an indicator of the importance and growth of probiotic use in pediatrics.
PMID- 27504148
TI - Oxidative Stress Assessment in Response to Ultraendurance Exercise: Thiols Redox
Status and ROS Production according to Duration of a Competitive Race.
AB - Purpose. Response to an ultraendurance competitive race on thiols redox status,
reactive oxygen species (ROS) production, and oxidative stress (OxS) was
investigated according to duration. Methods. Twenty-four elite runners were
examined: six completed 50 km and eighteen 100 km. Blood and urine samples were
collected before and immediately after the race. Erythrocytes and plasma
aminothiols by high-performance liquid chromatography, total antioxidant capacity
(TAC), and OxS biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive
substances (TBARS), 8-isoprostane (8-iso-PGF2alpha), and 8-OH-2-deoxyguanosine (8
OH-dG)) by immunoenzymatic assays and ROS production by Electron Paramagnetic
Resonance were assessed. Results. Significant increases (P between <0.05 and
<0.0001) were recorded in plasma total and oxidized aminothiols concentration and
TAC (P < 0.0001) only after 100 km: plasmatic (ROS production (+12 versus +29%),
PC (+54 versus +115%), and TBARS (+28 versus +55%)) and urinary (8-OH
dG.creatinine(-1) (+71 versus +158%) and 8-iso-PGF2alpha.creatinine(-1) (+43
versus +135%)) concentrations for 50 and 100 km (duration 4 h 3' versus 8 h 42'),
respectively. Conclusion. Very prolonged ultraendurance exercise causes an
increase in ROS production and OxS depending on specific biomarker examined but
always linearly and directly related to exercise duration. Redox status of
erythrocytes was preserved. A relationship between running performance and both
prerace ROS production and antioxidant-redox status was found in 100 km race.
PMID- 27504149
TI - "Cumulative Stress": The Effects of Maternal and Neonatal Oxidative Stress and
Oxidative Stress-Inducible Genes on Programming of Atopy.
AB - Although extensive epidemiological and laboratory studies have been performed to
identify the environmental and immunological causes of atopy, genetic
predisposition seems to be the biggest risk factor for allergic diseases. The
onset of atopic diseases may be the result of heritable changes of gene
expression, without any alteration in DNA sequences occurring in response to
early environmental stimuli. Findings suggest that the establishment of a
peculiar epigenetic pattern may also be generated by oxidative stress (OS) and
perpetuated by the activation of OS-related genes. Analyzing the role of maternal
and neonatal oxidative stress and oxidative stress-inducible genes, the purpose
of this review was to summarize what is known about the relationship between
maternal and neonatal OS-related genes and the development of atopic diseases.
PMID- 27504150
TI - Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and
Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and
Nuclear Factor-Kappa B.
AB - The mechanisms underlying intense exercise-induced liver damage and its potential
treatments remain unclear. We explored the hepatoprotection and mechanisms of
quercetin, a naturally occurring flavonoid, in strenuous exercise-derived
endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min
at a 5 degrees slope for 90 min) resulted in the leakage of aminotransferases in
the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress
levels were attenuated by quercetin (100 mg/kg.bw). Intense exercise and
thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and
inflammatory cytokines levels (IL-6 and TNF-alpha) were decreased with quercetin.
Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction,
Ca(2+) restoration, and blockade of the activities of Jun N-terminal kinase
(JNK), activating transcription factor 6 (ATF6) and especially NF-kappaB (p65 and
p50 nuclear translocation). A PI3K inhibitor abrogated the protection of
quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor),
AEBSF (ATF6 inhibitor), and especially PDTC (NF-kappaB inhibitor) enhanced the
quercetin-induced protection against Tg stimulation. Collectively, intense
exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt
activation and JNK, ATF6, and especially NF-kappaB suppression were involved in
the protection. Our results highlight a novel preventive strategy for treating
ERS and inflammation-mediated liver damage induced by intense exercise using
natural phytochemicals.
PMID- 27504151
TI - Effect of Gestational Diabetes on Purkinje and Granule Cells Distribution of the
Rat Cerebellum in 21 and 28 days of Postnatal Life.
AB - INTRODUCTION: Diabetes mellitus is associated with nervous system alterations in
both human and animal models. This study was done to determine the effect of
gestational diabetes on the Purkinje and granular cells in the cerebellum of rat
offspring. METHODS: 10 Wistar rats Dams were randomly allocated in control and
diabetic group. The experimental group received 40 mg/kg/body weight of
streptozotocin (STZ) at the first day of gestation and control groups received
saline injection intraperitoneally (IP). Six male offsprings of gestational
diabetic mothers and control dams, at the 21, 28 postnatal days were randomly
scarified and coronal sections of cerebellum (6 micrometer) serially collected.
The neurons were stained with cresyl violet. RESULTS: The Purkinje cells density
in the apex and depth of cerebellum in P21, in the experimental group was reduced
23% and 15% in comparison with the control group (P<0.001). The granular cells
density in the experimental group was reduced 19.58% and 18.3% in comparison with
the controls (P<0.001). The Purkinje cells density of cerebellum in P28, in the
diabetic group reduced to 22.12% and 12.62% in comparison with the control group
(P<0.001). The granular cells density in the diabetic group reduced 17.14% and
16.12% in comparison with the control group (P<0.001). DISCUSSION: The Purkinje
and granular cells significantly reduced in gestational diabetes rat offspring.
PMID- 27504152
TI - Effects of Increase in Amplitude of Occipital Alpha & Theta Brain Waves on Global
Functioning Level of Patients with GAD.
AB - INTRODUCTION: The basic objective of this study is to investigate the effects of
alpha and theta brain waves amplitude increase in occipital area on reducing the
severity of symptoms of generalized anxiety disorder and to increase the global
functioning level in patients with GAD. METHODS: This study is a quasi
experimental study with pre-test and post-test with two groups. For this purpose,
28 patients who had been referred to Sohrawardi psychiatric and clinical
psychology center in Zanjan were studied based on the interview with the
psychiatrist, clinical psychologist and using clinical diagnostic criteria for
the Diagnostic and Statistical Manual of Mental Disorders text revision - the DSM
IV-TR Fourth Edition diagnosis of GAD, 14 subjects were studied in neurofeedback
treatment group and 14 subjects in the waiting list group. Patients in both
groups were evaluated at pre-test and post-test with General Anxiety Disorder
Scale (GAD-7) and Global Assessment Functioning Scale (GAFs). The treatment group
received fifteen 30-minute alpha training sessions and fifteen 30-minute theta
brain training sessions in occipital area by neurofeedback training (treatment
group). This evaluation was performed according to the treatment protocol to
increase the alpha and theta waves. And no intervention was done in the waiting
list group. But due to ethical issues after the completion of the study all the
subjects in the waiting list group were treated. RESULTS: The results showed that
increase of alpha and theta brain waves amplitude in occipital area in people
with GAD can increase the global functioning level and can reduce symptoms of
generalized anxiety disorder in a treatment group, but no such change was
observed in the waiting list group. DISCUSSION: Increase of alpha and theta brain
waves amplitude in occipital area can be useful in the treatment of people with
GAD.
PMID- 27504153
TI - Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous
Morphine withdrawal Syndrome & Pain Sensation in Rats.
AB - INTRODUCTION: Methadone has been used as a drug to detoxify opioid tolerance.
Naloxane precipitated morphine withdrawal behaviours were attenuated by
venlafaxine as an antidepressant. On the contrary, after detoxifying the opioids,
spontaneous withdrawal syndrome may occur with pain sensitivity. Therefore the
present study aimed to examine the effects of chronic methadone (70 mg/kg, in
drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days)
and their combinations with the spontaneous morphine withdrawal syndrome and pain
sensitivity. METHODS: Twenty eight young male Sprague-Dawley rats were randomly
divided into 4 groups: control, venlafaxine treated, methadone treated and
venlafaxine + methadone treated. Morphine sulfate (10 mg/kg/day, subcutaneously,
4 days) was injected to all animals. Then primary withdrawal behaviours and tail
flick test were performed. The test was then followed by methadone or its vehicle
administration. Second intervention was venlafaxine or its vehicle injection.
Then final withdrawal behaviours and tail flick test were performed. RESULTS:
Combination of chronic methadone substitution and venlafaxine administration,
significantly reduced freezing behaviour of spontaneous morphine withdrawal
syndrome (P<0.01, 379+/-144%). Chronic methadone administration (P<0.05, 35+/-8%
difference with venlafaxine treated group) induced hyperalgesia. A positive
correlation (P=0.001, +63%) was observed between the animals final freezing
scores and their response latencies to the painful stimulus. DISCUSSION:
Combination of chronic methadone and venlafaxine administrations reduces freezing
withdrawal behaviour. Further investigations on analgesic interventions are
needed to overcome this hyperalgesia.
PMID- 27504154
TI - Effect of Cinnamomum Verum Extract on the Amyloid Formation of Hen Egg-white
Lysozyme and Study of its Possible Role in Alzheimer's Disease.
AB - INTRODUCTION: Diagnosing and treating diseases associated with amyloid fibers
remain a great challenge despite of intensive research carried out. One important
approach in the development of therapeutics is the use of herbal extracts which
are rich in aromatic small molecules. Cinnamomum verum extract (CE) contains
proanthocyanidin and cinnamaldehyde, which have been suggested to be capable of
directly inhibiting amyloid fibril formation in vitro. This study is aimed at
characterizing the inhibitory activity of CE against the fibrillation of hen egg
white lysozyme (HEWL). METHODS: Acidic pH and high temperatures were used to
drive the protein towards amyloid formation. Lysozyme was dissolved at 2 mg/mL in
50mM glycine buffer (pH 2.5), and then incubated at 57 degrees C for the
specified durations while stirred gently by Teflon magnetic bars. Various
techniques including thioflavin T, fluorescence, Congo red absorbance assay and
AFM micrography were used to characterize the HEWL fibrillation processes.
RESULTS: In the absence of CE typical amyloid fibrils (like amyloids formed in
Alzheimer disease) became evident after 48 h of incubation. Upon incubation with
various extract concentrations in the range of 0.1-1 mg/ml, formation of
fibrillar assemblies were significantly inhibited (P<0.05). AFM analysis and MTT
assay also confirmed the role of the extract in amyloid inhibition. Our studies
showed that the presence of CE did not have any effect on protein stabilization
and thus directly interact with amyloid structure and inhibit formation of these
structures. Furthermore, a docking experiment showed that a pi-pi interaction may
occur between the aromatic component of cinnamaldehyde and W62. Interestingly,
W62 is one of the principal aromatic residues that interact with glycine amide,
which is an aggregation suppressor of HEWL. DISCUSSION: These observations
suggest that aromatic small molecules of CE may directly insert into
amyloidogenic core of early aggregates and inhibit amyloid fibril formation by
disrupting the pi-pi interactions.
PMID- 27504155
TI - Group A beta-hemolytic Streptococcal Infection in Children and the Resultant
Neuro-psychiatric Disorder; a Cross Sectional Study; Tehran, Iran.
AB - INTRODUCTION: Group A Beta-Hemolytic Streptococcus (GABHS) can induce PANDAS
(pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infection). GABHS is the most important and common bacterial cause of acute
pharyngitis in Iranian children. We studied the role of GABHS (anti-streptococcal
antibodies) in suspected cases of PANDAS in a cross sectional studies. METHODS:
Across sectional study was done in 2 pediatric psychiatric/and neurologic clinics
in Tehran (Rasul Akram and Aliasghar Hospital) during 2008-2010. We studied serum
anti-streptococcal antibodies (anti streptolysin O, anti Deoxyribonuclease B, and
anti-streptokinase (ABcam-ELISA, USA) in 76 cases with psychiatric manifestation
(OCD, ADHD) in compare with 39 healthy controls. These antibodies were studied in
53 cases with movement disorders (Tic/Tourette syndrome) in compare with 76
healthy controls. Sensitivity, specificity and positive predictive value of tests
were calculated. RESULTS: In movement disorders ASOT, Anti-DNase and Anti
streptokinase was significantly higher than controls (P<0.0001, P=0.000,
P<0.00001) ASOT (cut off level> 200 IU/ml) had 75% sensitivity; 84% specificity
and 80% PPV; Anti-streptokinase (cut off level > 332 IU/ml) had 34% sensitivity;
85% specificity, and 72% PPV; Anti-DNase (cut off level > 140 IU/ml) had 70%
sensitivity; 99% specificity and PPV 90% for differentiating the group. ASOT,
Anti-DNase and Anti streptokinase titer was significantly higher than controls
(P<0.0001, P=0.000, P<0.0001). ASOT had 90% sensitivity; 82% specificity, PPV
92%; Anti streptokinase: 82% sensitivity; 82% specificity, PPV 95%; Anti DNase:
92% sensitivity; 82% specificity, PPV 92% for differentiation the cases from
normal controls. DISCUSSION: These findings support that a post infectious immune
mechanism to GABHS may play a role in the pathogenesis of PANDAS in our children.
A combination of throat culture, rapid antigen detection test, and serologic
testing for GABHS is required to achieve maximum sensitivity and specificity for
diagnosis. We prefer to use antibiotic prophylaxis in PANDAS cases for preventing
recurrent streptococcal infections. Ongoing research is needed for identifying
optimum diagnostic, prevention and therapeutic approach especially, aggressive
treatment (intravenous immunoglobulin, plasmaphresis).
PMID- 27504156
TI - Inter-pulse Interval Affects the Size of Single-pulse TMS-induced Motor Evoked
Potentials: A Reliability Study.
AB - INTRODUCTION: Measuring the size of motor evoked potentials (MEPs) induced by
transcranial magnetic stimulation (TMS) is an investigational technique to show
the level of corticospinal excitability; however, some of the fundamental
methodological aspects of TMS (such as the effects of inter-pulse intervals (IPI)
on MEP size) are not fully understood, this issue raises concerns about the
reliability of MEPs, especially in pre-test post-test studies. METHODS: MEP size
at short and long IPIs was assessed during two separate sessions. Inter- and
intra-session reliability of MEP size also was assessed at both short and long
IPIs. RESULTS: The results indicated that long IPIs induced larger MEPs (P< 0.05)
across all time points. The intra-class correlation coefficient (ICC) indicated
high intra- and inter-session reliability for short (0.87 to 0.96) and long (0.80
to 0.97) IPIs respectively. The amplitude of MEPs also had high intersession
reliability for short (ICC=0.87) and long (ICC = 0.80) IPIs. DISCUSSION: This
study provides evidence that the length of IPIs determines the size of MEPs. As a
result, it is recommended to add the length of IPI to the international checklist
of considerations for TMS application.
PMID- 27504157
TI - cAMP-Epac Pathway Stimulation Modulate Connexin-43 and MicroRNA-21 Expression in
Glioma Cells.
AB - INTRODUCTION: Malignant astrocytic gliomas are the most common and lethal brain
malignancies due to their refractory to the current therapies. Nowadays,
molecular targeted therapy has attracted great attention in treatment of glioma.
Connexin 43 (Cx43) and micro ribonucleic acid-21(miR-21) are among molecules that
are involved in glioma development and progression. These molecules showed
potential to be as target molecules with regard to glioma. Some studies have
reported that cyclic adenosine monophosphate (cAMP) signaling could be effective
on Cx43 and miR-21 in tissues other than in brain. We investigate possible
relationship between beta-adrenergic receptor and its newly described downstream,
exchange protein directly activated by cAMP (Epac) signaling pathway and
expression of Cx43 and miR-21 in low (1321N1) and high grade (U87MG) glioma cell
lines. METHODS: We treated cells with beta-adrenergic agonist and Epac activator
with and without adenyl cyclase inhibitor. Cx43 and miR-21 expression were
measured with real-time PCR. RESULTS: Our data showed that in 1321N1 cells, beta
adrenergic-Epac pathway stimulation up and down-regulated Cx43 and miR-21
expression respectively. Whereas, in U87MG cells these interventions had no
effect on Cx43 and miR-21 expression. DISCUSSION: These findings demonstrate that
low grade astrocytoma cells have better response to our pharmacological
interventions.
PMID- 27504158
TI - Evaluation of Hemodynamic Response Function in Vision and Motor Brain Regions for
the Young and Elderly Adults.
AB - INTRODUCTION: Prior studies comparing Hemodynamic Response Function (HRF) in the
young and elderly adults based on fMRI data have reported inconsistent findings
for brain vision and motor regions in healthy aging. It is shown that the
averaging method employed in all previous works has caused this inconsistency.
The averaging is so sensitive to outliers and noise. However, fMRI data are
obscured with a major contribution of noise particularly in the elderly case.
METHODS: Deconvolution algorithm is here proposed for HRF extraction to achieve
more robustness against noise. In spite of earlier works, proposed deconvolution
algorithm yields compatible HRF results using either original or denoised fMRI
data, though a large percentage of selected active voxels change in the latter
case. In the current study, event-related fMRI data have been used for 18
subjects (8 young and 10 elderly adults) with a simple visual and motor task of
pressing a key with index in response to the visual presentation of the word tap.
Considering anatomically-defined vision and motor regions and preprocessing steps
in FSL and SPM, the activated voxels have been selected according to t-test for
which HRF is estimated using deconvolution method. RESULTS: Experimental results
demonstrate that HRF peak amplitudes do not differ significantly (P=0.8) in the
vision region for the young and the elderly. In motor region, the HRF peak
significantly increases for the young compared to the elderly (P<0.03). Repeating
the procedure on the denoised fMRI data using MDL algorithm, the same results
have been obtained. DISCUSSION: In this study, a comparative study has been
realized on the hemodynamic response properties associated with the young and the
elderly adults on a simple visual and motor task.
PMID- 27504159
TI - A Qualitative Study to Identify Skills and Competency Required for Hospital
Managers.
AB - INTRODUCTION: Hospital managers aim to improve the efficiency and effectiveness
of their institutions through leadership and guidance of medical personnel.
Fulfilling these objectives requires a holistic approach to both the management
of people and institutional prioritization. The aim of this study was to identify
the skills and competencies that hospital managers must demonstrate in order to
achieve their objectives. METHODS: In 2015, a regional, multi-center qualitative
study was undertaken in Shiraz, Iran. Interviews and focus group discussions were
conducted with university hospital managers, senior managers, faculty members,
and post-graduate students, and the results were analyzed using the content
analysis method by MAXQDA software. RESULTS: Eight key skill themes
(communication, experience, appreciation of institution logistics/infrastructure,
management skills, motivation, systematic problem solving, ethics, and
financial/legal awareness) were identified among the hospital managers. The
common challenges that face hospital institutions include problems with
hierarchical and organizational structure, excessive rules and regulations, lack
of resources, poor post-graduate education, and overall management. Recurring
themes with respect to how these could be addressed included changing the culture
and belief structure of the hospital, restructuring the organizational hierarchy,
and empowering the people. CONCLUSION: In our cohort, practical skills, such as
communication and experience, were considered more important than theoretical
skills for the effective management and administration of hospitals. Therefore,
we suggest that practical, skill-based training should be emphasized for students
of these disciplines so they will be better suited to deal with real world
challenges. Further organizational improvements also can be attained by the
active and constructive involvement of senior university managers.
PMID- 27504160
TI - Mutational analysis of reverse transcriptase and surface proteins of patients
with partial virological response during mono and combination antiviral therapies
in genotype D chronic hepatitis B.
AB - INTRODUCTION: The mutational pattern of chronic Hepatitis B virus (HBV) is
unclear in patients who show incomplete response to antiviral therapy. The aims
of this study were 1) to determine the benefit of combination therapy with
adefovir dipivoxil (ADV) and Lamivudine (LAM) versus ADV or LAM alone in
maintaining virological, biochemical and histological responses and 2) to
investigate the patterns of mutations in the reverse transcriptase and surface
proteins of HBV with LAM and/or ADF-resistant in partially-responded chronic
hepatitis B (CHB) patients. METHODS: The study group consisted of 186 chronic HBV
carriers who were admitted to the Tehran Hepatitis Network from 2010 to 2013. We
retrospectively selected 86 patients who partially responded to different
nucleoside analogue regimens. After 48 weeks of therapy, five groups of patients
were defined including eight Lamivudine (LAM) Group (I), 30 Adefovir (ADV) Group
(II), 16 ADV add on LAM Group (III), 32 ADV+LAM Group (IV), and 100 controls (no
therapy). Reverse transcriptase (RT) and surface genes were amplified and
sequenced for mutational analysis. RESULTS: All groups showed differences between
mean values for age, gender, alanine transaminase (ALT), aspartate transaminase
(AST), and HBV DNA levels groups showed significant differences than other groups
(p < 0.05). The mutation frequencies for groups were I (1.7%), II (1.39%), III
(2.28%), IV (2.0%), and V (0.38%). T54N, L80I/V, I91L/V, L180M, M204I/V, Q215P/S,
and F221Y/S showed the highest number of mutations in all groups with different
frequencies. Four new, unreported mutations were found. CONCLUSION: Those
patients who failed to respond in the first 48 weeks, whether they were receiving
mono or combination therapy, should be tested genotypically, for the early
modification of treatment.
PMID- 27504161
TI - Effect of Processed Honey and Royal Jelly on Cancer-Related Fatigue: A Double
Blind Randomized Clinical Trial.
AB - BACKGROUND: Cancer-related fatigue (CRF) is experienced by 50% to 90% of cancer
patients and can severely affect their quality of life and functional capacity.
Several randomized trials have recommended various ways to alleviate the symptoms
of CRF with or without recourse to medications. OBJECTIVE: The aim of this study
is to evaluate the effectiveness of processed honey and royal jelly on the
symptoms of CRF in cancer patients who are undergoing hormone therapy,
chemotherapy, chemo-radiation, or radiotherapy. METHODS: Fifty-two participants
from the patients who visited the oncology clinic of Shohada-e-Tajrish hospital
in Tehran (Iran) between May 2013 and August 2014 were selected and divided into
two groups. The study group (26 patients) received processed honey and royal
jelly, while the control group received pure honey. Both groups were instructed
to consume their 5mL supplement twice daily for 4 weeks. Both groups were
assessed at the beginning of the study, after 2 weeks, and then at the end of 4
weeks of treatment. Fatigue was measured using a visual analogue fatigue scale
(VAFS) and fatigue severity scale (FSS). The results were compared between the
two arms of study, and equality of probability distributions was assessed using a
Kolmogorov-Smirnov test. RESULTS: The mean age of the 52 patients was 54.84.
After two and four weeks of treatment with processed honey and royal jelly, VAFS
and FSS due to treatment was better in the study group than in the control group,
and the differences were statistically significant (p<0.001, p<0.001,
respectively). CONCLUSION: To the best of our knowledge, our study provided
support for the use of processed honey and royal jelly to ameliorate CRF. The
positive results of this study warrant further studies in this field. CLINICAL
TRIAL REGISTRATION: The study was registered in the Iranian Clinical Trial
Registry Center (http://www.irct.ir) with the registration code:
IRCT2015081423426N1. FUNDING: The authors received no financial support for the
research, authorship, and/or publication of this article.
PMID- 27504162
TI - The link between bone disease and cardiovascular complications in hemodialysis
patients.
AB - INTRODUCTION: The burden on the cardiovascular system is the main cause of
mortality in chronic renal patients, and bone disease, which also may cause
disability, is one of the most important complications in those patients. The aim
of this study was to determine the link between cardiovascular and bone disease,
which frequently occur together. METHODS: In this matched case-control study, 70
subjects were subjected for full laboratory assessment as well as estimation of
parathyroid hormone (PTH) level, vitamin D level, complete echocardiography, and
dual energy absorptiometry. Of the 70 patients, 50 were on regular hemodialysis,
and there were 20 normal controls matched with the patients with respect to age
and gender. RESULTS: There was a significant decrease in the mean value of serum
vitamin D in the hemodialysis patients, i.e., their mean value was 20.47 +/- 9.60
whereas the controls had a mean value of 37.15 +/- 7.67. Thus, there was a highly
significant, negative correlation between vitamin D and left ventricular mass
(LVM) in the patients. We found that there was a highly-significant increase in
the mean PTH levels of the patients (820.22 +/- 393.51), whereas it was 57.60 +/-
13.72 for the controls. The statistical significance was less than 0.001, a
highly-significant increase in the mean of the T score levels in the patients (
2.15 +/- 2.56), whereas it was -0.47 +/- 0.71 for the controls with a statistical
significance of less than 0.001. There also was a highly-significant correlation
between the T score and LVM. CONCLUSION: A significant correlation was found
between bone disease and the occurrence of a left ventricular mass. We recommend
early strict correction of the serum levels of vitamin D, PTH, calcium, and
phosphorus.
PMID- 27504163
TI - Public sexual health promotion interventions and strategies: A qualitative study.
AB - INTRODUCTION: Sexual health promotion is the process of enabling people to
increase control over their sexual health that should be based on people's needs
and abilities. The aim of this study was to explore public sexual health
promotion interventions and strategies. METHODS: This study was a qualitative
content analysis approach. This qualitative study was a qualitative part of an
exploratory sequential qualitative-quantitative study that took place between
November 2014 and May 2015 and was conducted in Rasht, Iran. Data were collected
using semi-structured interviews with 38 engaged and married men and women as
well as nine key informants. The data were analyzed by the content analysis
method and by using qualitative data analysis software MAXqda 2011. RESULTS:
Analyzing participants' perspectives and experiences revealed two main
categories, i.e., 1) General actions to promote sexual health (with three sub
categories: public policies promoting sexual health, development of sexual health
supporting environments, and removal of barriers to receiving services) and 2)
Specific actions in the current health system (with three sub-categories:
economic policy, empowering individuals and the society, and reviewing the
current health system). CONCLUSIONS: General actions (public policies, supporting
environments developed, and removal of barriers to receiving services) and
integration of specific actions in the health system, such as empowering
individuals' needs for promoting sexual health. Achieving these goals
necessitates the review of the current health system in Iran.
PMID- 27504164
TI - Estimation of the residential radon levels and the annual effective dose in
dwellings of Shiraz, Iran, in 2015.
AB - INTRODUCTION: Radon is the second most important cause of lung cancer after
smoking. Thus, the determination of indoor radon concentrations in dwellings and
workplaces is an important public health concern. The purpose of this research
was to measure the concentration of radon gas in residential homes and public
places in the city of Shiraz and its relationship with the type and age of the
buildings as well as the type of materials used to construct the building (brick,
block). We also determined the radon dosages that occupants of the building would
receive. METHODS: The present study is a descriptive-analytical and cross
sectional research that was conducted on the building's indoor air in the city of
Shiraz in 2015. Using geographic information system (GIS) software and a spatial
sampling cell with an area of 25 square kilometers, 200 points were selected. In
this study, we used passive diffusive samplers as Solid State Nuclear Track
Detector (SSNTD) CR-39 polycarbonate films for three months in the winter.
Sampling was conducted in accordance with the U.S. Environmental Protection
Agency's protocol. We determined the concentrations of radon gas at the time of
sampling, and calibration factors were determined. The data were analyzed by IBM
SPSS, version 20, descriptive statistics, Kruskal-Wallis, and Mann-Whitney tests.
RESULTS: This study showed that the average radon concentration was 57.6 +/-
33.06 Bq/m(3) in residential dwellings. The average effective dose was 1.45
mSv/y. The concentration of radon in 5.4% of the houses was found to be greater
than 100 Bq/m(3), which is above the level allowed by the World Health
Organization (WHO). CONCLUSION: Since radon is the second leading cause of lung
cancer, it seems necessary to increase the public's awareness of this issue and
to take action to reduce radon in homes when the concentrations are above the
WHO's guideline.
PMID- 27504165
TI - Developing a conceptual model for the application of patient and public
involvement in the healthcare system in Iran.
AB - INTRODUCTION: Patient and public involvement is engaging patients, providers,
community representatives, and the public in healthcare planning and decision
making. The purpose of this study was to develop a model for the application of
patient and public involvement in decision making in the Iranian healthcare
system. METHODS: A mixed qualitative-quantitative approach was used to develop a
conceptual model. Thirty three key informants were purposely recruited in the
qualitative stage, and 420 people (patients and their companions) were included
in a protocol study that was implemented in five steps: 1) Identifying
antecedents, consequences, and variables associated with the patient and the
publics' involvement in healthcare decision making through a comprehensive
literature review; 2) Determining the main variables in the context of Iran's
health system using conceptual framework analysis; 3) Prioritizing and weighting
variables by Shannon entropy; 4) designing and validating a tool for patient and
public involvement in healthcare decision making; and 5) Providing a conceptual
model of patient and the public involvement in planning and developing healthcare
using structural equation modeling. We used various software programs, including
SPSS (17), Max QDA (10), EXCEL, and LISREL. Content analysis, Shannon entropy,
and descriptive and analytic statistics were used to analyze the data. RESULTS:
In this study, seven antecedents variable, five dimensions of involvement, and
six consequences were identified. These variables were used to design a valid
tool. A logical model was derived that explained the logical relationships
between antecedent and consequent variables and the dimensions of patient and
public involvement as well. CONCLUSION: Given the specific context of the
political, social, and innovative environments in Iran, it was necessary to
design a model that would be compatible with these features. It can improve the
quality of care and promote the patient and the public satisfaction with
healthcare and legitimate the representative of people they served for. This
model can provide a practical guide for managers and policy makers to involve
people in making the decisions that influence their lives.
PMID- 27504166
TI - Features of a Health-Oriented Education Program during Daily Commutes: A
Qualitative Study.
AB - INTRODUCTION: Today, despite scientific advances, many people spend more time and
distance between home and their workplaces because of various economic and
population reasons. The aim of this study was to identify features of an
appropriate health education program during commutes for factory staff at Ardakan
county (Yazd province, Iran). METHODS: This qualitative study was conducted via
the phenomenological method in 2014. The population of this study was members of
the staff of Ardakan Steel Company. Nineteen specialists and 11 members of the
factory's staff were invited to participate in the study, and data were collected
using semi-structured interviews. The interviews took 20 to 40 minutes, and their
content was analyzed using content analysis. RESULTS: Extraction of codes and
themes and their placement in this study showed that an educational program
during commutes should have nine features to have the desired effectiveness,
i.e., the program must be audience-oriented, repeatable, participatory,
technology-based, combinational, supportive, and motivational and interesting.
Also, the program should have environmental and organizational support, and it
must be evaluated for its effectiveness. CONCLUSION: Considering appropriate
features of a health education program in educational situations, especially
interventions related to daily commutes, is very important because the
effectiveness of such health-oriented educational programs must be ensured.
PMID- 27504167
TI - Expectation of fairness: a turning point in the professional satisfaction of
Iranian nurses.
AB - INTRODUCTION: The professional satisfaction of staff is one of the most
challenging organizational concepts that can enhance the efficiency level of
organizations. In a similar vein, the professional satisfaction of nurses is of
considerable importance, in that, professional dissatisfaction among nurses could
result in emotional detachment, depression, anger, evasion from work, and
inefficacy and would negatively impact the organization's work rate. The aim of
this study was to understand Iranian nurses' experiences of the concept of
professional satisfaction. METHODS: This was a qualitative study conducted with a
targeted sampling of 10 nurses (4 men and 6 women) in 2015. The data were
collected through conducting in-depth interviews, and textual data were analyzed
subsequently using the Qualitative Content Analysis (QCA) method. RESULTS: The
findings of this study pointed to "fair conduct," which was comprised of three
sub-categories, i.e., expectation of fairness in social-professional settings,
expectation of fairness in receiving professional benefits, and expectation of
fairness in the area of professional interactions. CONCLUSIONS: There are various
ups and downs in nursing due to the challenging nature of the profession, from
the initial education at the university until retirement. According to the
findings of this study, a lack of fairness in social-professional settings, a
lack of fairness in receiving professional benefits, and a lack of fairness in
the area of professional interactions were among the factors that have great
impacts on the degree of professional dissatisfaction among nurses.
PMID- 27504168
TI - Nanocomposites in food packaging applications and their risk assessment for
health.
AB - Nanotechnology has shown many advantages in different fields. As the uses of
nanotechnology have progressed, it has been found to be a promising technology
for the food packaging industry in the global market. It has proven capabilities
that are valuable in packaging foods, including improved barriers; mechanical,
thermal, and biodegradable properties; and applications in active and intelligent
food packaging. Examples of the latter are anti-microbial agents and nanosensors,
respectively. However, the use of nanocomposites in food packaging might be
challenging due to the reduced particle size of nanomaterials and the fact that
the chemical and physical characteristics of such tiny materials may be quite
different from those of their macro-scale counterparts. In order to discuss the
potential risks of nanoparticles for consumers, in addition to the quantification
of data, a thorough investigation of their characteristics is required. Migration
studies must be conducted to determine the amounts of nanomaterials released into
the food matrices. In this article, different applications of nanocomposites in
food packaging, migration issues, analyzing techniques, and the main concerns
about their usage are discussed briefly.
PMID- 27504169
TI - The Results of Autologous Skin Test in Patients with Chronic Urticaria in
Hamadan, Iran.
AB - INTRODUCTION: The etiology of chronic urticaria is unknown in many cases. In this
study, we demonstrated the presence of autoimmune antibodies in patients with
chronic urticaria by using of the Autologous Serum Skin Test (ASST). METHODS: We
performed a cross-sectional study to detect the presence of autologous antibodies
in the serum of 38 patients (25 females and 13 males) with idiopathic chronic
urticaria who were referred to the Hamedan Allergy Clinic in 2014. All of the
necessary tests for demonstrating chronic urticaria were performed, including
complete blood count (CBC), thyroid and liver functionality tests, and the prick
test but they did not confirm the cause of chronic urticaria. We conducted the
Autologous Serum Skin Test on the patients and analyzed the results. RESULTS: In
15 patients (39%), the ASST was positive. Of the 15 patients with positive
autoimmune chronic urticaria, five patients (33%) were males, and 10 patients
(67%) were females. CONCLUSION: We concluded that many patients with chronic
urticaria have autoimmune urticaria. It is the reason for the lack of the
response to treatment with common medications for urticaria. New ways of
treatment must be considered for them.
PMID- 27504170
TI - Laparoscopic Repair of Perforated Peptic Ulcer: Outcome and Associated Morbidity
and Mortality.
AB - INTRODUCTION: The mainstay of treatment for perforated peptic ulcer is Omental
patch closure. With the advent of laparoscopic surgery, this approach is being
used for the treatment of perforated peptic ulcer. The aim of this study was to
evaluate the outcome of laparoscopy in Firoozgar general hospital over a period
of 18 months. The outcome of the laparoscopic approach and the associated
morbidity and mortality, operation time, conversion rate and hospital stay were
assessed. METHODS: A prospective analysis of 29 consecutive patients (mean age
37.5 years; 23 men) with perforated peptic ulcers and who had undergone
laparoscopic surgery was carried over a period of 18 months from March 2014 until
September 2015. Pre-operative, intra-operative, and post-operative clinical data
were collectively analyzed by SPSS 19 for Windows. RESULTS: Seventeen patients
had a history of cigarette smoking, 11 patients had a history of opium
consumption, 19 were chronic NSAID users, 26 had Helicobacter pylori infections,
and six had a co-morbid condition. Previous surgical history included laparotomy
for pancreatic cancer in two patients, for sigmoid colon cancer in one patient,
and for acute appendicitis in four patients. The average operating time for all
cases was 47.5 + 20 min. The mean lag time between onset of symptoms and surgery
was 20.4 hours. All patients underwent laparoscopic closure of the perforation
with Omental patch closure. No morbidity was observed, and none of the patients
needed conversion to open surgery. One patient died after 11 months of follow-up
due to the progression of underlying pancreatic cancer. The mean postoperative
hospital stay was 4.2 days. CONCLUSIONS: The results of the laparoscopic approach
for perforated peptic ulcer were promising, with no conversion to open surgery,
no morbidity, and mortality.
PMID- 27504171
TI - Investigating the Relationship between Insulin-like Growth Factor-1 (IGF-1) in
diabetic mother's breast milk and the blood serum of their babies.
AB - INTRODUCTION: Since research investigating IGF-1 levels in breast milk are few,
the goal of this study was to analyze the IGF-1 levels in the breast milk of
diabetic mothers as well as in the serum of their newborn babies and to identify
what relationship exists between blood serum and IGF-1 milk levels through
patient measurement of mothers and their babies. METHODS: This case control study
was undertaken under the auspices of the Clinic of Neonatology at Al Minia
University Pediatric Hospital over May 2012 through May 2013. With a total of 30
diabetic mothers and their babies forming the experimental group and the control
group consisting of 15 non-diabetic mothers and their babies. A detailed medical
history, anthropometric assessments, as well as the measurement of the baby's
serum IGF-1 and their mother's breast milk IGF-1 levels were taken from all
participants using ELSIA. The resulting data were analyzed via Statistical
Package for the Social Sciences (SPSS) version 16 and measurements of descriptive
statistics, t-test, Chi-square test, as well as the Pearson Correlation
Coefficient. RESULTS: The Infants born to Diabetic Mothers (IDMs) demonstrated
significantly greater anthropometric measurement. Both the serum levels and the
milk IGF-1 levels as well as all of the physical measurements taken were found to
have a positive correlation between the level of IGF-1 in mother's milk and all
of the anthropometric measurements studied with the exception of delivered baby's
length. CONCLUSION: Higher levels of IGF-1 are present in the milk of diabetic
mothers and the blood serum of their babies and this characteristic could be used
as a prenatal biomarker for macrosomia.
PMID- 27504172
TI - Socio-Economic Factors Influencing on Total Fertility Rate in Iran: A Panel Data
Analysis for the Period of 2002-2012.
AB - INTRODUCTION: Over the last few decades, total fertility rate (TFR) has followed
a downward trend in Iran. The consequences of this trend from the perspectives of
some are negative. Considering the macro-population policies in recent years,
this study aimed to examine the effect of some macro socio-economic variables,
including divorce, marriage, urbanization, and unemployment rate on TFR in Iran
from 2002 to 2012. METHODS: This time series research was conducted in 2015 using
the databases of the National Organization for Civil Registration (NOCR) and the
Statistical Center of Iran. The study population was the related data of
provinces in the selected variables. The main methods used in the research were
the common unit root test, Pedroni Cointegration test, redundant fixed effects
tests, correlated random effects-Hausman test, and panel least squares of fixed
effects. In order to determine the suitable model for estimating panel data,
likelihood ratio and Huasman tests were done using Eviews software, and the fixed
effects regression model was chosen as the dominant model. RESULTS: The results
indicated that the divorce rate had a negative and significant effect on TFR (p <
0.05). A positive and significant relationship between marriage rate and TFR
variables also was observed (p < 0.05). Urbanization rate (p = 0.24) and
unemployment rate (p = 0.36) had no significant relationship with TFR. According
to F statistic, significance of the overall model also was confirmed (p < 0.001).
CONCLUSION: Due to the lower effect of the studied factors on the reduction of
TFR, it seems that variables other than the ones studied, as well as cultural
factors and values, might be fundamental factors for this change in the country.
PMID- 27504173
TI - Isolation, Identification, and In Vitro Antifungal Susceptibility Testing of
Dermatophytes from Clinical Samples at Sohag University Hospital in Egypt.
AB - AIM: The objective of this study was to isolate, identify, and explore the in
vitro antifungal susceptibility pattern of dermatophytes isolated from clinically
suspected cases of dermatophytosis (tinea infections) attending the Dermatology
Outpatient Clinic. METHODS: This study was conducted at Sohag University Hospital
from December 2014 to December 2015. Clinical samples (e.g., skin scrapings and
hair stumps) were collected under aseptic precautions. The identification of
dermatophytes was performed through microscopic examination using 10% potassium
hydroxide (KOH) with 40% dimethyl sulphoxide (DMSO) mounts and culture on
Sabouraud dextrose agar (SDA) and on Dermasel agar base media, both supplemented
with chloramphenicol and cycloheximide. All dermatophytes isolates were subjected
to antifungal susceptibility testing using the agar-based disk diffusion (ABDD)
method against Clotrimazole, Miconazole, Fluconazole, and Griseofulvin. Data were
analyzed via SPSS 16, using Chi square and a screening test (cross-tabulation
method). RESULTS: A total of 110 patients of dermatophytosis were studied. The
patients were clinically diagnosed and mycologically confirmed as having tinea
capitis (49), tinea corporis (30), tinea pedis (16), tinea cruris (9), or tinea
barbae (6). The dermatophytes isolates belonged to 4 species: Microsporum canis
58 (52.7%), Microsporum gypseum 23 (20.9%), Trichophyton mentagrophytes 18
(16.4%), and Microsporum audouinii 11 (10%). The most effective antifungal drugs
tested were Clotrimazole, followed by Miconazole (95.5% and 84.5% of isolates
were susceptible, respectively). CONCLUSION: Every patient with a tinea infection
should be properly studied for a mycological examination and should be treated
accordingly. Dermasel agar is more useful as an identification medium in the
isolation of dermatophytes. The ABDD method appears to be a simple, cost
effective, and promising method for the evaluation of antifungal susceptibility
of dermatophytes.
PMID- 27504174
TI - The Abortificient Effects of Hydroalcoholic Extract of Lawsonia Inermis on BALB/c
Mice.
AB - INTRODUCTION: According to the traditional beliefs of certain cultures, Lawsonia
inermis has been reported to cause the abortion or termination of an undesirable
pregnancy. The present study was undertaken with the goal of studying the effect
of Lawsonia inermis extract on abortion in pregnant BALB/c mice in 2013 in
Shahrekord, Iran. METHODS: This research study used an experimental methodology
and was conducted in 2013 in Shahrekord, Iran. Forty female BALB/c mice (30-40
gm, 8-12 weeks old) were randomly assigned to 4 groups. One male mouse was
included for each two female mice (1:2) and they were maintained in a protective
cage habitat. Pregnancy of the mice was confirmed by means of a vaginal smear.
The doses of 1 mg/kg and 10 mg/kg of the hydroalcoholic extract of Lawsonia
inermis were injected intraperitoneally into pregnant mice beginning on the first
day and continuing through the seventh day of pregnancy. The control group did
not receive any treatment, but was left completely unadministered. On the
eighteenth day of pregnancy, the uterine tubes of mice were removed. The
subsequent embryonic absorption is considered to be an abortion. The data were
analyzed using SPSS software version 22 using Fisher's exact test and the Kruskal
Wallis H tests. RESULTS: Abortions were observed more often in the experimental
groups (p< 0.01). The mean of the serum estrogen level was significantly higher
in the case control groups (p< 0.01) and the mean of progesterone level was also
significantly lower in the experimental groups (p< 0.01). CONCLUSION: The use of
Lawsonia inermis during pregnancy may cause abortion and therefore it should be
considered as contraindication or use with caution.
PMID- 27504176
TI - Anthropometric Profiling of New Zealand Junior Elite Triathletes.
AB - INTRODUCTION: The triathlon involves a combination of three separate disciplines
swimming, cycling and running. To date, very few studies have been conducted on
the anthropometric characteristics of the New Zealand junior elite triathletes.
The aim of this study was to determine the correlation between physical traits of
calf girth or sum of eight skinfolds (anthropometry) and running or cycling
performances in the triathlon event. METHODS: Eleven junior elite triathletes (6
females, 5 males; (Av. age: 17) who were selected for the New Zealand national
squad, were examined in this cross-sectional study. All athletes were measured
for the complete anthropometric profile, as per the International Society for
Advancement of Kinanthropometry (ISAK) guidelines. It was then correlated with
the cycling and running performances using interclass correlation (ICC) with 90%
confidence interval (CI) limits. RESULTS: A non-significant positive correlation
observed between eight skinfolds tests on running performance (ICC: 0.10; 90% CI:
-0.68-0.77; p>0.05) and biking performance (ICC: 0.15; 90% CI: -0.65-0.79;
p>0.05), suggested athletes with greater body fat may render a better athletic
performance. Conversely, a significant negative correlation was observed between
calf girth and running performance (ICC:-0.66; 90% CI: -0.94 - -0.12; p<0.05) and
a non-significant negative correlation was observed between calf girth and
cycling performance (ICC:-0.94; 90% CI: -0.97- 0.68; p>0.05). CONCLUSION:
Anthropometric data can help in predicting an ideal body profile. This research
indicates the similarities and differences of the New Zealand junior profile and
the world junior profile.
PMID- 27504175
TI - Visual Detection of Enterohemorrhagic Escherichia coli O157:H7 Using Loop
Mediated Isothermal Amplification.
AB - INTRODUCTION: Escherichia coli O157:H7, an important foodborne pathogen, can
cause serious renal damage, which can also lead to mortality. Since a rapid and
sensitive method is needed to identify this pathogenic agent, we evaluated Loop
Mediated Isothermal Amplification Assay (LAMP) to detect Escherichia coli
O157:H7. METHODS: We used six primers that specifically identified the rfbE gene.
To examine the sensitivity of the method, different dilutions were subjected to
the LAMP reaction. Other bacterial strains also were investigated to determine
the specificity of the test. The turbidity of the amplified products was assayed
by visual detection. The amplified products were detected by addition of SYBR
Green II to the reaction tubes. RESULTS: Amplification products were observed as
a ladder-like pattern on the agarose gel. A white turbidity emerged in the
positive tubes. Under UV light, the positive samples were green, whereas the
negative samples were orange. The detection limit of the LAMP was 78 pg/tube, and
this indicated that it was 100 times more sensitive than PCR for the detection of
EHEC. No LAMP products were detected when template DNA of non-EHEC strains were
used, suggesting high specificity of the LAMP assay. CONCLUSION: The results
indicated that the LAMP assay is a valuable diagnostic assay to identify EHEC
O157:H7. In addition, the simplicity, sensitivity, specificity, and rapidity of
this assay make it a useful method to diagnose pathogens in primary labs without
any need for expensive equipment or specialized techniques.
PMID- 27504177
TI - Severe angina pectoris in asthma attack: a case report.
AB - Asthma is a chronic inflammatory disorder of the airways related to the
obstruction of reversible airflow. Asthma presents as recurrent attacks of cough
and dyspnea. Poor control causes recurrent admissions to the ICU, and mortality
is related to poor drug compliance and follow-up. Angina pectoris is a syndrome
of recurrent chest discomfort related to myocardial ischemia. The presence of
these two disorders rarely has been reported. We reported a 12-year-old boy who
was referred with exacerbation of asthma and developed angina pectoris during
hospitalization. He had labored breathing and diffuse wheezing. During treatment
of the asthma, the patient developed severe chest pain due to shunt formation and
coronary hypoxia, caused by the sole administration of ventolin, since oxygen had
been disconnected. After receiving appropriate therapy, both his asthma and
angina recovered, and, to date, he has not experienced angina pectoris again.
PMID- 27504178
TI - Embracing change: striated-for-smooth muscle replacement in esophagus
development.
AB - The esophagus functions to transport food from the oropharyngeal region to the
stomach via waves of peristalsis and transient relaxation of the lower esophageal
sphincter. The gastrointestinal tract, including the esophagus, is ensheathed by
the muscularis externa (ME). However, while the ME of the gastrointestinal tract
distal to the esophagus is exclusively smooth muscle, the esophageal ME of many
vertebrate species comprises a variable amount of striated muscle. The esophageal
ME is initially composed only of smooth muscle, but its developmental maturation
involves proximal-to-distal replacement of smooth muscle with striated muscle.
This fascinating phenomenon raises two important questions: what is the
developmental origin of the striated muscle precursor cells, and what are the
cellular and morphogenetic mechanisms underlying the process? Studies addressing
these questions have provided controversial answers. In this review, we discuss
the development of ideas in this area and recent work that has shed light on
these issues. A working model has emerged that should permit deeper understanding
of the role of ME development and maturation in esophageal disorders and in the
functional and evolutionary underpinnings of the variable degree of esophageal
striated myogenesis in vertebrate species.
PMID- 27408685
TI - "The molecule's the thing:" the promise of molecular modeling and dynamic
simulations in aiding the prioritization and interpretation of genomic testing
results.
AB - Clinical genomics is now a reality and lies at the heart of individualized
medicine efforts. The success of these approaches is evidenced by the increasing
volume of publications that report causal links between genomic variants and
disease. In spite of early success, clinical genomics currently faces significant
challenges in establishing the relevance of the majority of variants identified
by next generation sequencing tests. Indeed, the majority of mutations identified
are harbored by proteins whose functions remain elusive. Herein we describe the
current scenario in genomic testing and in particular the burden of variants of
uncertain significance (VUSs). We highlight a role for molecular modeling and
molecular dynamic simulations as tools that can significantly increase the yield
of information to aid in the evaluation of pathogenicity. Though the application
of these methodologies to the interpretation of variants identified by genomic
testing is not yet widespread, we predict that an increase in their use will
significantly benefit the mission of clinical genomics for individualized
medicine.
PMID- 27429748
TI - High quality, small molecule-activity datasets for kinase research.
AB - Kinases regulate cell growth, movement, and death. Deregulated kinase activity is
a frequent cause of disease. The therapeutic potential of kinase inhibitors has
led to large amounts of published structure activity relationship (SAR) data.
Bioactivity databases such as the Kinase Knowledgebase (KKB), WOMBAT, GOSTAR, and
ChEMBL provide researchers with quantitative data characterizing the activity of
compounds across many biological assays. The KKB, for example, contains over 1.8M
kinase structure-activity data points reported in peer-reviewed journals and
patents. In the spirit of fostering methods development and validation worldwide,
we have extracted and have made available from the KKB 258K structure activity
data points and 76K associated unique chemical structures across eight kinase
targets. These data are freely available for download within this data note.
PMID- 27504181
TI - Assessing the sensitivity and representativeness of the Belgian Sentinel Network
of Laboratories using test reimbursement data.
AB - BACKGROUND: The Belgian Sentinel Network of Laboratories (SNL) was created in
1983 in order to monitor trends in infectious diseases. Given the evolution of
the surveillance system, such as the waivers, fusions and adhesions of
laboratories over time, it is important to evaluate whether the SNL is still fit
for purpose. This study aims to evaluate aspects of the sensitivity and
representativeness of the SNL by means of a test coverage analysis. METHODS: We
estimated test coverage of the SNL using the ratio of reimbursed tests performed
by participating laboratories to the total number of tests performed between 2007
and 2012, for 12 (groups of) pathogens. We further evaluated the geographical
difference coverage of the SNL at regional and provincial levels. RESULTS: We
found that test coverage of the SNL was stable over time and close to, or greater
than, 50 % for the 12 (groups of) pathogens studied. These results hold for the
three regions of Belgium but not for all provinces. We showed that some provinces
had a low test coverage for some pathogens and that test coverage was more
variable over time at provincial level. CONCLUSIONS: This sensitivity and
representativeness study based on test coverage suggests that the SNL is capable
to describe trend and to monitor changes in the 12 (groups of) pathogens studied
both at national and regional levels. Therefore, the SNL is useful to contribute
to estimate the burden of disease and to inform preventive measures. It should
however be reinforced to allow to be used as an alert system at provincial level.
PMID- 27504182
TI - The association between varicella (chickenpox) and group A streptococcus
infections in historical perspective.
AB - OBJECTIVES: The aim of the research is to investigate the historical relationship
between varicella and Streptococcus pyogenes infections. In the past few decades,
varicella has been identified as a risk factor for invasive group A streptococcus
infections. The question is whether this relationship also existed between
varicella and scarlet fever in the historical era. METHODS: The analysis begins
with a search of historical medical reports on the relationship between varicella
and scarlet fever epidemics in the late 19th and early 20th century, as well as
in more recent empirical studies. Correlations and cross-correlations between
varicella and scarlet fever are analyzed using weekly public health case reports
from 1924 to 1932 for Boston, Chicago, New York City, and Philadelphia.
Regression models are used to estimate the relationship between varicella and
scarlet fever after controlling for seasonal forcing. RESULTS: Historical records
give limited support for a causal relationship between varicella and scarlet
fever but indicate that these diseases often occurred close in time to each
other. Likewise, statistical analysis shows that varicella and scarlet fever
epidemics are closely aligned with each other, and varicella has a strong
relationship with scarlet fever. The relationship is stronger than reported in
any previous research on the two diseases. CONCLUSION: The close correspondence
of the two diseases likely depends on multiple factors, including seasonal
forcing, a causal relationship, and co-infections. The results raise questions
about whether this close relationship might have had a synergistic effect or a
role in the evolution of S. pyogenes from the virulent, high incidence epidemics
of the 19th century to the relatively benign scarlet fever of the 1950s.
PMID- 27504183
TI - Is medical perspective on clinical governance practices associated with clinical
units' performance and mortality? A cross-sectional study through a record
linkage procedure.
AB - OBJECTIVE: Assessment of the knowledge and application as well as perceived
utility by doctors of clinical governance tools in order to explore their impact
on clinical units' performance measured through mortality rates and efficiency
indicators. METHODS: This research is a cross-sectional study with a
deterministic record-linkage procedure. The sample includes n = 1250 doctors (n =
249 chiefs of clinical units; n = 1001 physicians) working in six public
hospitals located in the Emilia-Romagna Region in Italy. Survey instruments
include a checklist and a research-made questionnaire which were used for data
collection about doctors' knowledge and application as well as perceived utility
of clinical governance tools. The analysis was based on clinical units'
performance indicators which include patients' mortality, extra-region active
mobility rate, average hospital stay, bed occupancy, rotation and turnover rates,
and the comparative performance index as efficiency indicators. RESULTS: The
clinical governance tools are known and applied differently in all the considered
clinical units. Significant differences emerged between roles and organizational
levels at which the medical leadership is carried out. The levels of knowledge
and application of clinical governance practices are correlated with the clinical
units' efficiency indicators (bed occupancy rate, bed turnover interval, and
extra-region mobility). These multiple linear regression analyses highlighted
that the clinical governance knowledge and application is correlated with
clinical units' mortality rates (odds ratio, -8.677; 95% confidence interval,
16.654, -0.700). CONCLUSION: The knowledge and application, as well as perceived
utility by medical professionals of clinical governance tools, are associated
with the mortality rates of their units and with some efficiency indicators.
However, the medical frontline staff seems to not consider homogeneously useful
the clinical governance tools application on its own clinical practice.
PMID- 27504184
TI - Clinical impact and risk stratification of balloon angioplasty for
femoropopliteal disease in nitinol stenting era: Retrospective multicenter study
using propensity score matching analysis.
AB - OBJECTIVE: Nitinol stenting could bring the better outcome in endovascular
therapy for femoropopliteal disease. However, it might be expected that recent
marked advances in both device technology and operator technique had led to
improved efficacy of balloon angioplasty even in this segment. The aims of this
study were to evaluate the clinical impact of balloon angioplasty for
femoropopliteal disease and make risk stratification clear by propensity score
matching analysis. METHODS: Based on the multicenter retrospective data, 2758
patients (balloon angioplasty: 729 patients and nitinol stenting: 2029 patients),
those who underwent endovascular therapy for femoropopliteal disease, were
analyzed. RESULTS: The propensity score matching procedure extracted a total of
572 cases per group, and the primary patency rate of balloon angioplasty and
nitinol stenting groups after matching was significantly the same (77.2% vs 82.7%
at 1 year; 62.2% vs 64.3% at 3 years; 47.8% vs 54.3% at 5 years). In multivariate
Cox hazard regression analysis, significant predictors for primary patency were
diabetes mellitus, regular dialysis, cilostazol use, chronic total occlusion, and
intra-vascular ultra-sonography use. The strategy of balloon angioplasty was not
evaluated as a significant predictor for the primary patency. After risk
stratification using five items (diabetes mellitus, regular dialysis, no use of
intra-vascular ultra-sonography, chronic total occlusion, and no use of
cilostazol: the DDICC score), the estimated primary patency rates of each group
(low, DDICC score 0-2; moderate, DDICC score 3; high risk, DDICC score 4-5) were
88.6%, 78.3%, and 63.5% at 1 year; 75.2%, 60.7%, and 39.8% at 3 years; and 66.0%,
47.1%, and 26.3% at 5 years (p < 0.0001). The primary patency rate of balloon
angioplasty and nitinol stenting groups was significantly the same in each risk
stratification. CONCLUSION: This study suggests that balloon angioplasty does not
have inferiority to nitinol stenting but does have favorable efficacy in
femoropopliteal segment by careful risk stratification with the recent advance of
technique.
PMID- 27504185
TI - Effects of electrical stimulation therapy on the blood flow in chronic critical
limb ischemia patients following regenerative therapy.
AB - OBJECTIVES: We investigated the effects of electrical stimulation therapy on
cutaneous and muscle blood flow in critical limb ischemia patients following
regenerative therapy. METHODS: Three groups were studied: 10 healthy young
subjects, 10 elderly subjects, and 7 critical limb ischemia patients after
regenerative therapy. After 5 min rest, electrical stimulation was applied at 5
Hz on the tibialis anterior muscle for 10 min. We estimated the relative changes
in oxyhemoglobin and total hemoglobin compared to the basal values at rest
(Delta[HbO2], Delta[Hbtot]), which reflected the blood flow in the skin and
muscle layer, and we simultaneously measured the tissue O2 saturation (StO2)
throughout the electrical stimulation and recovery phase by near-infrared
spectroscopy. RESULTS: The Delta[HbO2] and Delta[Hbtot] values of the muscle
layer in critical limb ischemia patients increased gradually and remained
significantly higher at the 5-min and 10-min recovery periods after the
electrical stimulation without reducing the StO2, but there is no significant
change in the other two groups. Skin blood flow was not influenced by electrical
stimulation in three groups. CONCLUSION: This improvement of the peripheral
circulation by electrical stimulation would be beneficial as the adjunctive
therapy after regenerative cell therapy.
PMID- 27504186
TI - Cell-based laboratory evaluation of coagulation activation by antineoplastic
drugs for the treatment of lymphoid tumors.
AB - OBJECTIVES: Combining vorinostat, L-asparaginase, and doxorubicin (Dox) led to
improved response rates in the treatment of lymphoid tumors. However, deep-vein
thrombosis has been noted as one of the most serious side effects with these
drugs, and how these regimens cause deep-vein thrombosis is unclear. METHODS: We
investigated the procoagulant effects of vorinostat, L-asparaginase, and
doxorubicin in lymphoid tumors, focusing on tissue factor, phosphatidylserine,
and antithrombin. The human vascular endothelial cell line EAhy926 as well as the
lymphoid neoplastic cell lines HUT78 (cutaneous T-cell lymphoma), Molt4 (acute T
lymphoblastic leukemia), and Ramos (Burkitt lymphoma) were employed to
investigate these procoagulant effects. RESULTS: Vorinostat, L-asparaginase, and
doxorubicin induced exposure of phosphatidylserine and procoagulant activity on
the surface of lymphoid tumor cells. Vorinostat and doxorubicin also induced
phosphatidylserine exposure and increased procoagulant activity on EAhy926 cells.
Expression of tissue factor antigen was induced by doxorubicin on the surface of
each type of cells, whereas expression of tissue factor mRNA was unchanged.
Secretion of antithrombin from HepG2 cells was reduced only by L-asparaginase.
CONCLUSION: These data suggest that vorinostat and doxorubicin may induce
procoagulant activity in vessels through apoptosis of tumor cells and through
phosphatidylserine exposure and/or tissue factor expression on vascular
endothelial cells. L-asparaginase may induce a thrombophilic state by reducing
the secretion of anticoagulant proteins such as antithrombin. The laboratory
methods described here could be useful to evaluate the procoagulant effects of
antineoplastic drugs.
PMID- 27504187
TI - "Varibaculum massiliense" sp. nov., a new bacterial species isolated from human
urine.
AB - We report the main characteristics of "Varibaculum massiliense" strain Marseille
P2802(T) (=CSUR P2802), which was isolated from urine sample of a 59-year-old man
with end-stage renal disease.
PMID- 27504188
TI - A case of laryngeal cancer induced by exposure to asbestos in a construction site
supervisor.
AB - BACKGROUND: Construction site supervisors are exposed to many chemicals, dusts,
and metals including asbestos. Asbestos is a hazardous chemical that is
carcinogenic. Laryngeal cancer is not a rare disease in Korea. The most common
causes of this disease are tobacco and alcohol, and representative occupational
cause is asbestos. However, up to now, no case of laryngeal cancer induced by
asbestos has been reported in Korea. In this study, we report such a case in a
construction site supervisor. CASE PRESENTATION: A 60-year-old man who had been
experiencing hoarseness for 2 months was diagnosed with laryngeal cancer. The
pathologic diagnosis was squamous cell carcinoma in situ, based on examination of
a biopsy specimen obtained by resection of the lesion. The patient had been
exposed to asbestos for 38 years at construction sites where he worked until
diagnosed with laryngeal cancer. He had been exposed to asbestos when demolishing
buildings and inspecting materials. CONCLUSION: The patient in this case worked
with construction materials including asbestos and supervised construction for 38
years, and was thus exposed to asbestos at construction sites. Much of the
asbestos was highly concentrated especially during demolition processes. We
therefore consider the laryngeal cancer of this patient to be a work-related
disease.
PMID- 27504189
TI - IgA nephropathy in a laboratory worker that progressed to end-stage renal
disease: a case report.
AB - BACKGROUND: IgA nephropathy (IgAN) is the most common form of glomerulonephritis,
a principal cause of end-stage renal disease (ESRD) worldwide. The mechanisms of
onset and progression of IgAN have not been fully revealed, and epidemiologic
studies have yielded diverging opinions as to the role of occupational exposure
to organic solvents in the initiation or worsening of IgAN. As the authors
encountered a laboratory worker with IgAN that progressed to ESRD, we present a
case report of IgAN progression due to dichloromethane exposure along with a
review of literature. CASE PRESENTATION: A 41-year-old male laboratory worker
began to experience gross painless hematuria after two years of occupational
exposure to toluene. Although clinical follow-up was initiated under the
impression of IgAN based on clinical findings, the patient continued to work for
four more years in the same laboratory, during which he was in charge of
laboratory analysis with direct exposure to a high concentration of
dichloromethane without proper protective equipment. During that time, his renal
function rapidly worsened and finally progressed to ESRD 10 years after the first
clinical symptoms. The result of exposure assessment through reenactment of his
work exceeded the occupational exposure limit for dichloromethane to a
considerable degree. CONCLUSIONS: The causal association between occupational
solvent exposure and IgAN is still unclear; therefore, this case report could be
used as a basis to support the relevance of occupational solvent exposure to IgAN
and/or its progression. Early intervention as well as close monitoring of
laboratory workers exposed to various organic solvents is important to prevent or
delay the progression of glomerulonephritis to ESRD in the occupational setting.
PMID- 27504190
TI - Pharmacokinetics and dose adjustment of etoposide administered in a medium-dose
etoposide, cyclophosphamide and total body irradiation regimen before allogeneic
hematopoietic stem cell transplantation.
AB - BACKGROUND: We investigated the pharmacokinetics of etoposide (ETP) to reduce the
inter-individual variations of ETP concentrations in patients with acute leukemia
who underwent allogeneic hematopoietic stem cell transplantation. We also carried
out an in vivo study using rats to verify the dose adjustment. METHODS: This
study included 20 adult patients. ETP was administered intravenously at a dose of
15 mg/kg once daily for 2 days (total dose: 30 mg/kg) combined with standard
conditioning of cyclophosphamide and total body irradiation. In an in vivo study
using rats, ETP was administered intravenously at a dose of 15 mg/kg or an
adjusted dose. The ETP plasma concentration was determined by using HPLC. The
pharmacokinetic parameters were estimated by using a 1-compartment model.
RESULTS: The peak concentration (Cmax) of ETP and the area under the plasma
concentration-time curve (AUC) of ETP differed greatly among patients (range of
Cmax, 51.8 - 116.5 MUg/mL; range of AUC, 870 - 2015 MUg . h/mL). A significant
relationship was found between Cmax and AUC (R = 0.85, P < 0.05). Distribution
volume (Vd) was suggested to be one of the factors of inter-individual variation
in plasma concentration of ETP in patients (range of Vd, 0.13 - 0.27 L/kg), and
correlated with Alb and body weight (R = 0.56, P < 0.05; R = 0.40, P < 0.05
respectively). We predicted Vd of rats by body weight of rats (with normal
albumin levels and renal function), and the dose of ETP was adjusted using
predicted Vd. In the dose adjustment group, the target plasma ETP concentration
was achieved and the variation of plasma ETP concentration was decreased.
CONCLUSION: The results suggested that inter-individual variation of plasma
concentration of ETP could be reduced by predicting Vd. Prediction of Vd is
effective for reducing individual variation of ETP concentration and might enable
a good therapeutic effect to be achieved.
PMID- 27504191
TI - Effect of choline chloride supplementation on milk production and milk
composition of Etawah grade goats.
AB - BACKGROUND: The effect of choline chloride supplementation through forced
drinking combined with concentrate diets containing Ca-fish oil on milk
production and milk composition of Etawah Grade goats was evaluated. Choline
chloride is an essential component in ruminant diets as it is required for fat
metabolism. METHOD: The experiment was conducted in a completely randomized block
design with three types of treatments and eight replications. The trial had two
successive experimental periods; the first, during the eight weeks of late
pregnancy, and the second, during the first 12 weeks of lactation. Twenty-four
Etawah Grade does in the second gestation period were divided into three
treatment groups. Commercial choline chloride 60 % in corncobs-based powder was
used as a source of choline chloride. The treatments were no supplementation
(control) and supplemented with either 4 g or 8 g/2days of choline chloride.
Choline chloride was given to the animals through a forced drinking technique,
after dissolving it in 60 ml drinking water. The initial body weight of does was
38.81 +/- 3.66 kg. The does were penned individually, and were given fresh
chopped King Grass ad libitum and 700 g/day of concentrate diets containing Ca
fish oil, starting eight weeks prior to expecting kidding and continuing for 12
weeks of parturition. RESULTS: All nutrient intakes were not significantly
different (p > 0.05) among the treatments during the late pregnancy and the
lactation periods. Supplementation did not affect (p > 0.05) the average daily
gains and feed conversion ratio during pregnancy but gave effects (p < 0.05) on
the average daily gains, feed conversion ratio and income over feed cost during
lactation. The highest average daily milk yields and 4 % fat corrected milk
yields were found in goats supplemented with 4 g/2days of choline chloride and
increased by 17.00 % and 24.67 %, respectively, compared to the control.
Moreover, milk composition percentage and milk constituent yields improved
significantly (p < 0.05) in those supplemented with 4 g/2days of choline
chloride. CONCLUSION: The supplementation of 4 g/2days of choline chloride
through forced drinking increased milk yields, the 4 % fat corrected milk yields,
milk composition, milk constituent yields, and improved feed conversion ratio and
income over feed cost of Etawah Grade goats.
PMID- 27504192
TI - CT findings associated with blastic plasmacytoid dendritic cell neoplasm: a case
report.
AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic
malignancy that is frequently misdiagnosed. We present a case of a 53-year-old
man diagnosed with blastic plasmacytoid dendritic cell neoplasm with extensive
computed tomography (CT) findings and provide an imaging focused review of this
uncommon malignancy.
PMID- 27504193
TI - Testicular microlithiasis and preliminary experience of acoustic radiation force
impulse imaging.
AB - BACKGROUND: Elastography of the testis can be used as a part of multiparametric
examination of the scrotum. PURPOSE: To determine the testicular stiffness using
acoustic radiation force impulse imaging (ARFI) technique in men with testicular
microlithiasis (TML). MATERIAL AND METHODS: In 2013, 12 patients with diagnosed
testicular microlithiasis in 2008 (mean age, 51 years; age range, 25-76 years)
underwent a 5-year follow-up B-mode ultrasonography with three ARFI elastography
measurements of each testis. We used a Siemens Acuson S3000 machine. RESULTS: No
malignancy was found at the 5-year follow-up B-mode and elastography in 2013.
However, we found an increase in TML; in the previous ultrasonography in 2008,
eight men had bilateral TML, whereas in 2013, 10 men were diagnosed with
bilateral TML. The mean elasticity of testicles with TML was 0.82 m/s
(interquartile range [IQR], 0.72-0.88 m/s; range, 65-1.08 m/s). CONCLUSION:
Elastography velocity of testis with TML seems to be in the same velocity range
as in men with normal testis tissue.
PMID- 27504194
TI - Duplication of the superficial femoral artery: comprehensive review of imaging
literature and insight into embryology.
AB - An extremely rare case of duplicated superficial femoral artery (SFA) was
incidentally observed on computed tomography angiogram (CTA) of the lower limbs
for presurgical planning for an osteomyocutaneous fibula flap in a patient with
T4a oropharyngeal squamous cell carcinoma (SCC). To our knowledge, this is the
sixth reported case in the imaging literature. We performed a comprehensive
review of the English literature and discuss the underlying embryological origin
underpinning this rare anatomical variant.
PMID- 27504195
TI - The Effects of Scleral Collagen Cross-Linking Using Glyceraldehyde on the
Progression of Form-Deprived Myopia in Guinea Pigs.
AB - To investigate the effects of collagen cross-linking using glyceraldehyde on the
biomechanical properties of the sclera and the axial elongation of form-deprived
myopia in the guinea pig. Thirty-six guinea pigs were randomly assigned to four
groups: FDM (form-deprived myopia); FDMG (form-deprived myopia treated with
glyceraldehyde); FDMS (form-deprived myopia treated with 0.9% isotonic sodium
chloride); and normal control (free of form-deprivation). FDM was achieved in the
right eye using a latex facemask. The right eye in FDMG was treated with a
posterior subtenon injection of 0.5 M glyceraldehyde; 0.9% isotonic sodium
chloride was administered to the right eye in FDMS group using the same method.
Axial length, refraction, and stress-strain of the sclera were measured at
scheduled time points. The treated eyes were also examined histologically by
light microscopy. It was found that glyceraldehyde treatment significantly
increased the stiffness of the sclera in the FDM eyes and abnormalities have not
been observed in the retina and optic nerve of the treated eyes. But the
development of myopia was not affected.
PMID- 27504196
TI - Expression of TSLP and Downstream Molecules IL-4, IL-5, and IL-13 on the Eye
Surface of Patients with Various Types of Allergic Conjunctivitis.
AB - Background. The pathogenesis of allergic conjunctivitis has not been clearly
established. Moreover, previous studies fail to consider human models of allergic
conjunctivitis. This study investigated the expression of thymic stromal
lymphopoiet in TSLP and its downstream molecules in conjunctival scrappings and
tear. Methods. This cross-sectional study compares patients with vernal
keratoconjunctivitis (VKC), seasonal allergic conjunctivitis (SAC), and perennial
allergic conjunctivitis (PAC) with normal controls. There are 80 people recorded
in Shanxi Eye Hospital. Increasingly, 20 are with VKC, 20 are with SAC, 20 are
with PAC, and the remaining 20 are normal controls. Conjunctiva were harvested
for total RNA extraction and gene expression by real-time polymerase chain
reaction. Epithelial cells were collected to make pathological sections for
immunohistochemical staining. Human tears were evaluated by Luminex microbead
assay. A P value less than 0.05 from Dunnett's post hoc test in SPSS means a
statistical significant distinction. Results. Positive expression in conjunctival
cells of patients with allergic conjunctivitis. The expression of TSLP and IL-4,
IL-5, and IL-13 mRNA shows a statistically significant difference (P < 0.05).
TSLP and IL-4, IL-5, and IL-13 concentrations show a statistically significant
difference (P < 0.01). Conclusions. This study suggests that TSLP and downstream
molecules are expressed in patients with various types of allergic
conjunctivitis.
PMID- 27504197
TI - Effect of exercise on serum vitamin D and tissue vitamin D receptors in
experimentally induced type 2 Diabetes Mellitus.
AB - This work aimed to study the effect of swimming exercise on serum vitamin D level
and tissue vitamin D receptors in experimentally induced type 2 Diabetes
Mellitus. Sixty adult male rats were divided into control and diabetic groups.
Each was further subdivided into sedentary and exercised subgroups. Diabetes
Mellitus was induced by a single intraperitoneal dose of streptozotocin (50
mg/kg) dissolved in cold 0.01 M citrate buffer (pH 4.5). The exercised subgroups
underwent swimming for 60 min, 5 times a week for 4 weeks. Serum glucose,
insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids,
vitamin D and tissue Vitamin D receptors (VDR) were evaluated. Significant
increase in serum glucose, insulin, HOMA-IR, cholesterol, triglycerides, and low
density lipoprotein (LDL) levels in sedentary diabetic rats was detected. On the
other hand, high density lipoprotein (HDL), free fatty acids, serum vitamin D and
pancreatic, adipose, and muscular VDR showed a significant decrease in the same
group. It is evident that all these parameters were reversed by swimming exercise
indicating its beneficial role in type 2 Diabetes. In diabetic groups; serum
vitamin D was found to be correlated negatively with serum glucose, insulin,
HOMA, cholesterol, triglycerides, and LDL and positively correlated with HDL and
tissue VDR. In conclusion, Disturbed vitamin D is associated with metabolic
impairments in sedentary diabetic rats. Moderate swimming exercise is beneficial
in improving these consequences through modulation of vitamin D status. Future
studies could be designed to investigate the effect of the combination of vitamin
D intake with exercise in diabetic patients.
PMID- 27504198
TI - Metabolomics driven analysis of Erythrina lysistemon cell suspension culture in
response to methyl jasmonate elicitation.
AB - An MS-based metabolomic approach was used to profile the secondary metabolite of
the ornamental plant Erythrina lysistemon via ultra-performance liquid
chromatography coupled to photodiode array detection and high resolution q-TOF
mass spectrometry (UPLC-PDA-MS). Cultures maintained the capacity to produce E.
lysistemon flavonoid subclasses with pterocarpans amounting for the most abundant
ones suggesting that it could provide a resource of such flavonoid subclass. In
contrast, alkaloids, major constituents of Erythrina genus, were detected at
trace levels in suspension cultures. Methyl jasmonate (MeJA), phytohormone, was
further supplied to culture with the aim of increasing secondary metabolites
production and with metabolite profiles subjected to multivariate data analysis
to evaluate its effect. Results revealed that triterpene i.e. oleanolic acid and
fatty acid i.e. hydroxy-octadecadienoic acid were elicited in response to methyl
jasmonate, whereas pterocarpans i.e., isoneorautenol showed a decline in response
to elicitation suggesting for the induction of terpenoid biosynthetic pathway and
concurrent with a down regulation of pterocarpans. In conclusion, a total of 53
secondary metabolites including 3 flavones, 12 isoflavones, 4 isoflavanones, 4
alkaloids, 11 pterocarpans, and 5 phenolic acids were identified.
PMID- 27504199
TI - Using Multidisciplinary Focus Groups to Inform the Development of mI SMART: A
Nurse-Led Technology Intervention for Multiple Chronic Conditions.
AB - Used as integrated tools, technology may improve the ability of healthcare
providers to improve access and outcomes of care. Little is known about
healthcare teams' preferences in using such technology. This paper reports the
findings from focus groups aimed at evaluating a newly developed primary care
technology platform. Focus groups were completed in academic, outpatient, and
community settings. Focus groups were attended by 37 individuals. The
participants included professionals from multiple disciplines. Both prescribing
(N = 8) and nonprescribing healthcare team members (n = 21) completed the focus
groups and survey. The majority were practicing for more than 20 years (44.8%) in
an outpatient clinic (62%) for 20-40 hours per week (37.9%). Providers identified
perceived obstacles of patient use as ability, willingness, and time. System
obstacles were identified as lack of integration, lack of reimbursement, and
cost. The positive attributes of the developed system were capability for virtual
visits, readability, connectivity, user-friendliness, ability to capture
biophysical measures, enhanced patient access, and incorporation of multiple
technologies. Providers suggested increasing capability for biophysical and
symptom monitoring for more common chronic conditions. Technology interventions
have the potential to improve access and outcomes but will not be successful
without the input of users.
PMID- 27504200
TI - Bilateral Breast Reconstruction with Abdominal Free Flaps: A Single Centre,
Single Surgeon Retrospective Review of 55 Consecutive Patients.
AB - Breast reconstruction using free tissue transfer is an increasingly utilised
oncoplastic procedure. The aim was to review all bilateral breast reconstructions
using abdominal free flaps by a single surgeon over an 11-year period (2003
2014). A retrospective review was performed on all patients who underwent
bilateral breast reconstruction using abdominal free flaps between 2003 and 2014
by the senior author (DAM). Data analysed included patient demographics,
indication for reconstruction, surgical details, and complications. Fifty-five
female patients (mean 48.6 years [24-71 years]) had bilateral breast
reconstruction. The majority (41, 74.5%) underwent immediate reconstruction and
DIEP flaps were utilised on 41 (74.5%) occasions. Major surgical complications
occurred in 6 (10.9%) patients, all of which were postoperative vascular
compromise of the flap. Failure to salvage the reconstruction occurred on 3
(5.5%) occasions resulting in a total flap failure rate of 2.7%. Obesity (>30
kg/m(2)) and age > 60 years were shown to have a statistically increased risk of
developing postoperative complications (P < 0.05). Our experience demonstrates
that abdominal free flaps for bilateral breast reconstruction fares well, with a
flap failure rate of 2.7%. Increased body mass index and patient age (>60 years)
were associated with higher complication rates.
PMID- 27504201
TI - Healthy Aging from the Perspectives of 683 Older People with Multiple Sclerosis.
AB - Purpose. The aim of this study was to determine what factors most greatly
contributed to healthy aging with multiple sclerosis (MS) from the perspective of
a large sample of older people with MS. Design and Methods. Participants (n =
683; >55 years of age with symptoms >20 years) provided answers to an open-ended
question regarding healthy aging and were categorized into three groups, 55-64
(young), 65-74 (middle), and 75 and over (oldest old). Sociodemographic actors
were compared using ANOVA. Two independent raters used the framework method of
analyzing qualitative data. Results. Participants averaged 64 years of age (+/
6.2) with MS symptoms for 32.9 years (+/-9.4). 531 participants were female
(78%). The majority of participants lived in their own home (n = 657) with a
spouse or partner (n = 483). Participants described seven themes: social
connections, attitude and outlook on life, lifestyle choices and habits, health
care system, spirituality and religion, independence, and finances. These themes
had two shared characteristics, multidimensionality and interdependence.
Implications. Learning from the experiences of older adults with MS can help
young and middle aged people with MS plan to age in their own homes and
communities. Our data suggests that older people with MS prioritize factors that
are modifiable through targeted self-management strategies.
PMID- 27504202
TI - Pregnant Women in Louisiana Are Not Meeting Dietary Seafood Recommendations.
AB - Background. The 2015-2020 Dietary Guidelines for Americans recommend that
pregnant women and women of childbearing ages consume 8-12 oz. of seafood per
week. Fish are the major dietary source of omega-3 long chain polyunsaturated
fatty acids, which have benefits for the mother and fetus. Methods. In this
observational study, we investigated dietary habits of pregnant women in Baton
Rouge, Louisiana, USA, to determine if they achieve recommended seafood intake. A
print survey, which included commonly consumed foods from protein sources (beef,
chicken, pork, and fish), was completed by pregnant women at a single-day
hospital convention for expecting families in October 2015. Women (n = 221) chose
from six predefined responses to answer how frequently they were consuming each
food. Results. Chicken was consumed most frequently (75% of women), followed by
beef (71%), pork (65%), and fish (22%), respectively. Consumption frequency for
the most consumed fish (catfish, once per month) was similar to or lower than
that of the least consumed beef, chicken, and pork foods. Consumption frequency
for the most consumed chicken and beef foods was at least once per week.
Conclusion. Our data indicate that pregnant women in Louisiana often consume
protein sources other than fish and likely fail to meet dietary seafood
recommendations.
PMID- 27504203
TI - Cross-Cultural Adaptation and Validation of the Jebsen-Taylor Hand Function Test
in an Italian Population.
AB - Objective. This paper describes the Italian translation and adaptation to the
Italian culture of the original version of the Jebsen-Taylor hand function test
and conveys the procedure for testing its validity and reliability. Design. The
cultural adaptation process and validation were based on data from a group of
people with no clinical evidence of disease or impairment of the upper limbs. The
process required a forward and reverse translation in its original language. The
scale obtained was reviewed by 8 experts in the field of psychometrics dealing
with statistical methods that are useful for the behavioral and social sciences.
The Italian adapted version of the JTHFT was then produced and validated.
Participants. The test was submitted to 320 people with no clinical evidence of
disease in order to test its acceptability and consistency. Results. The total
time required to perform each subtest was 80.16 +/- 43.13 seconds for the
nondominant hand (NDH) and 49.97 +/- 27.28 seconds for the dominant hand (DH).
The internal consistency (assessed with Pearson's r) and the reliability or the
construct validity (assessed with Cronbach's alpha) are significative.
Conclusions. This is the first study reporting the result of the translation,
cultural adaptation, and validation protocols of the JTHFT in Italian. It
provides a new tool for Italian professionals to measure the functionality of the
hand in participants with various upper limb pathologies.
PMID- 27504204
TI - Altered Cerebellar Circuitry following Thoracic Spinal Cord Injury in Adult Rats.
AB - Cerebellar function is critical for coordinating movement and motor learning.
However, events occurring in the cerebellum following spinal cord injury (SCI)
have not been investigated in detail. We provide evidence of SCI-induced
cerebellar synaptic changes involving a loss of granule cell parallel fiber input
to distal regions of the Purkinje cell dendritic tree. This is accompanied by an
apparent increase in synaptic contacts to Purkinje cell proximal dendrites,
presumably from climbing fibers originating in the inferior olive. We also
observed an early stage injury-induced decrease in the levels of cerebellin-1, a
synaptic organizing molecule that is critical for establishing and maintaining
parallel fiber-Purkinje cell synaptic integrity. Interestingly, this
transsynaptic reorganizational pattern is consistent with that reported during
development and in certain transgenic mouse models. To our knowledge, such a
reorganizational event has not been described in response to SCI in adult rats.
Regardless, the novel results of this study are important for understanding SCI
induced synaptic changes in the cerebellum, which may prove critical for
strategies focusing on promoting functional recovery.
PMID- 27504205
TI - Dexamethasone Associated ST Elevation Myocardial Infarction Four Days after an
Unremarkable Coronary Angiogram-Another Reason for Cautious Use of Steroids: A
Case Report and Review of the Literature.
AB - Drug induced myocardial infarction is a known entity with different forms of
steroids linked to coronary artery disease (CAD) either through promoting its
traditional risk factors, inducing coronary spasm, or by other unidentified
mechanisms. Dexamethasone is known to promote an atherogenic and hypercoagulable
state. We report a case of a 75-year-old woman who had ST elevation myocardial
infarction (STEMI) associated with dexamethasone use just 4 days following an
angiogram showing minor luminal irregularities.
PMID- 27504206
TI - Testicular Signet-Ring Cell Metastasis from a Carcinoma of Unknown Primary Site:
A Case Report and Literature Review.
AB - Signet-ring cell carcinoma is a highly malignant adenocarcinoma consisting of
cells characterized as cytoplasmic vacuoles filled with mucin. The most common
primary location of this type of cancer is the stomach, but it may also be found
in other organs such as prostate, testis, bladder, ovaries, or colon. To date,
metastatic signet-ring cell carcinoma of unknown primary (CUP) site to the testis
is an extremely rare entity in daily practice. Reviewing the literature, we have
been able to detect only three cases of testicular metastases from CUP, two with
histological diagnosis of a signet-ring cell carcinoma and one with an
adenocarcinoma. In this short paper, we report a case of a 56-year-old man who
presented to our Department with testicular mass and ascites. Following a
standard diagnostic approach no primary tumor could be identified. CUP was the
final clinical diagnosis, histologically characterized as poorly differentiated
adenocarcinoma with signet-ring cells involving the peritoneum and the testicular
structures.
PMID- 27504207
TI - Spontaneous Minced Cartilage Procedure for Unexpectedly Large Femoral Condyle
Surface Defect.
AB - Articular cartilage defects at the knee joint are being identified and treated
with increasing frequency. Chondrocytes may have strongest potential to generate
high-quality repair tissue within the defective region, in particular when large
diameter defects are present. Autologous chondrocyte implantation is not
available in every country. We present a case where we spontaneously covered an
acute cartilage defect, which was significantly larger than expected and loose
during initial arthroscopic inspection after reading preoperative MRI, by mincing
the separated fragment and directly implanting the autologous cartilage chips
into the defective region.
PMID- 27504208
TI - Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease.
AB - Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated
vasculitis but it is rarely seen during the course of other connective tissue
diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci
immune crescentic glomerulonephritis in patients with connective tissue disease
other than vasculitis. We reviewed literature and made summary of previously
reported cases of this rare entity. Clinical and laboratory features of these
patients varied widely, but most of patients have met criteria for lupus. In this
small population of patients there is no correlation with ANCAs. Most of the
patients were treated with aggressive immunosuppression and did well if they were
treated early in the course of their disease. One of our patients required renal
transplant, but she presented late in the course of her disease, as evidenced by
chronicity on her renal biopsy. Whether these patients are overlap of vasculitis
and other connective tissue diseases or to be considered as a separate entity is
yet to be described. Clinicians must be aware of these presentations because
initial presentation can be severe.
PMID- 27504209
TI - Synthesis of Polymerizable Cyclodextrin Derivatives for Use in Adhesion-Promoting
Monomer Formulations.
AB - The synthesis of the cyclodextrin derivatives reported herein was assisted by
extensive literature research together with structure-property relationships
derived from three-dimensional molecular modeling. These studies led to the
hypothesis that many of the 21 hydroxyl groups on beta-cyclodextrin molecules
could be derivatized to form a closely related family of analogous chemical
compounds containing both polymerizable groups and hydrophilic ionizable ligand
(substrate-binding) groups, each attached via hydrolytically-stable ether
linkages. The vinylbenzylether polymerizable groups should readily homopolymerize
and also copolymerize with methacrylates. This could be highly useful for dental
applications because substantially all contemporary dental resins and composites
are based on methacrylate monomers. Due to hydrophilic ligands and residual
hydroxyl groups, these cyclodextrin derivatives should penetrate hydrated layers
of dentin and enamel to interact with collagen and tooth mineral. Analyses
indicated that the diverse reaction products resulting from the method of
synthesis reported herein should comprise a family of copolymerizable molecules
that collectively contain about 30 different combinations of vinylbenzyl and
hexanoate groups on the various molecules, with up to approximately seven of such
groups combined on some of the molecules. Although the hypothesis was supported,
and adhesive bonding to dentin is expected to be significantly improved by the
use of these polymerizable cyclodextrin derivatives, other efforts are planned
for improved synthetic methods to ensure that each of the reaction-product
molecules will contain at least one copolymerizable moiety. The long-term
objective is to enable stronger and more durable attachments of densely cross
linked polymers to hydrated hydrophilic substrates. Capabilities for bonding of
hydrolytically stable polymers to dental and perhaps other hydrous biological
tissues could provide widespread benefits.
PMID- 27504210
TI - Adhesive Bonding to Dentin Improved by Polymerizable Cyclodextrin Derivatives.
AB - The objective of this work was to determine bonding characteristics of a
hydrophilic monomer formulation containing polymerizable cyclodextrin
derivatives. The hypothesis was that a formulation containing hydrophilic cross
linking diluent comonomers and cyclodextrins with functional groups attached by
hydrolytically stable ether linkages could form strong adhesive bonds to dentin.
The previously synthesized polymerizable cyclodextrin derivatives were formulated
with sorbitol dimethacrylate, methacrylic acid and phenylbis(2,4,6
trimethylbenzoyl) phosphine oxide photoinitiator. The same formulation without
the polymerizable cyclodextrin derivatives isolated the effects of the
polymerizable cyclodextrin derivatives. A commercial self-etching bonding system
was tested as a comparative control. Ground mid-coronal dentin was etched with 37
% phosphoric acid (H3PO4) for 15 s and rinsed with distilled water for 10 s.
Formulations were applied to the moist dentin and light-cured 10 s. A packable
composite was then applied through irises and light-cured 60 s. Teeth were stored
in water for 24 h before bonds were tested in a shearing orientation. One-way
ANOVA was performed on the data. The average values of shear bond strengths were
defined as loads at fracture divided by the 4 mm diameter iris areas. The average
value of shear bond strength for the formulation containing the polymerizable
cyclodextrin derivatives was higher (p < 0.05), where p is a fraction of the
probability distribution) than that of the same monomeric formulation except that
the polymerizable cyclodextrin derivatives were not included. This was supporting
evidence that the polymerizable cyclodextrin derivatives contributed to improved
bonding. The average value of shear bond strength for the formulation containing
the polymerizable cyclodextrin derivatives was also higher (p < 0.05) than that
of the commercial self-etching bonding system. These preliminary results are in
accordance with the hypothesis that formulations containing polymerizable
cyclodextrin derivatives can form strong adhesive bonds to hydrated dentin
surfaces. Further improvements in bonding to hydrated biological tissues by use
of advanced formulations are anticipated.
PMID- 27504211
TI - ASME B89.4.19 Performance Evaluation Tests and Geometric Misalignments in Laser
Trackers.
AB - Small and unintended offsets, tilts, and eccentricity of the mechanical and
optical components in laser trackers introduce systematic errors in the measured
spherical coordinates (angles and range readings) and possibly in the calculated
lengths of reference artifacts. It is desirable that the tests described in the
ASME B89.4.19 Standard [1] be sensitive to these geometric misalignments so that
any resulting systematic errors are identified during performance evaluation. In
this paper, we present some analysis, using error models and numerical
simulation, of the sensitivity of the length measurement system tests and two
face system tests in the B89.4.19 Standard to misalignments in laser trackers. We
highlight key attributes of the testing strategy adopted in the Standard and
propose new length measurement system tests that demonstrate improved sensitivity
to some misalignments. Experimental results with a tracker that is not properly
error corrected for the effects of the misalignments validate claims regarding
the proposed new length tests.
PMID- 27504213
TI - Implementation of Two-Dimensional Polycrystalline Grains in Object Oriented
Micromagnetic Framework.
AB - In response to the growing need for a more accurate micromagnetic model to
understand switching phenomenon in nanoscale magnets, we developed the capability
to simulate two-dimensional polycrystalline grains using the Object Oriented
Micromagnetic Framework (OOMMF). This addition allows users full flexibility in
determining the magnetocrystalline anisotropy and axe in each grain as well as
the inter- and intragranular exchange coupling strength.
PMID- 27504212
TI - Statistical Analysis of a Round-Robin Measurement Survey of Two Candidate
Materials for a Seebeck Coefficient Standard Reference Material.
AB - In an effort to develop a Standard Reference Material (SRMTM) for Seebeck
coefficient, we have conducted a round-robin measurement survey of two candidate
materials-undoped Bi2Te3 and Constantan (55 % Cu and 45 % Ni alloy). Measurements
were performed in two rounds by twelve laboratories involved in active
thermoelectric research using a number of different commercial and custom-built
measurement systems and techniques. In this paper we report the detailed
statistical analyses on the interlaboratory measurement results and the
statistical methodology for analysis of irregularly sampled measurement curves in
the interlaboratory study setting. Based on these results, we have selected
Bi2Te3 as the prototype standard material. Once available, this SRM will be
useful for future interlaboratory data comparison and instrument calibrations.
PMID- 27504214
TI - Measurement of Absorption and Scattering With an Integrating Sphere Detector:
Application to Microalgae.
AB - A spectrometer with an integrating sphere (IS) detector was used to measure the
absorbance due to scattering and absorption. Analysis of the measurement process
showed that two measurements of the absorbance, one with the cuvette placed in
the normal spectrometer position, and the second with the cuvette placed next to
the entrance aperture of the IS detector, provide enough information to separate
the contributions from scattering and molecular absorption. Measurements were
carried out with mixtures of microsphere and chromophore solutions. Two cases
were examined: microspheres suspended in an aqueous fluorescein solution, and
microspheres suspended in an aqueous holmium oxide solution. In both cases, the
proposed measurement model gave results which were in good agreement with the
expected response. Measurements on microalgae suspensions yielded a molecular
absorption contribution and a scattering contribution. The scattering
contribution had significant spectral structure which was inversely related to
the molecular absorption contribution. The absorption and scattering
contributions may provide independent information on the status of chlorophyll
molecules and the structure of chloroplasts in microalgae.
PMID- 27504215
TI - Issues in Optical Diffraction Theory.
AB - This paper focuses on unresolved or poorly documented issues pertaining to
Fresnel's scalar diffraction theory and its modifications. In Sec. 2 it is
pointed out that all thermal sources used in practice are finite in size and
errors can result from insufficient coherence of the optical field. A quarter
wave criterion is applied to show how such errors can be avoided by placing the
source at a large distance from the aperture plane, and it is found that in many
cases it may be necessary to use collimated light as on the source side of a
Fraunhofer experiment. If these precautions are not taken the theory of partial
coherence may have to be used for the computations. In Sec. 3 it is recalled that
for near-zone computations the Kirchhoff or Rayleigh-Sommerfeld integrals are
applicable, but fail to correctly describe the energy flux across the aperture
plane because they are not continuously differentiable with respect to the
assumed geometrical field on the source side. This is remedied by formulating an
improved theory in which the field on either side of a semi-reflecting screen is
expressed as the superposition of mutually incoherent components which propagate
in the opposite directions of the incident and reflected light. These components
are defined as linear combinations of the Rayleigh-Sommerfeld integrals, so that
they are rigorous solutions of the wave equation as well as continuously
differentiable in the aperture plane. Algorithms for using the new theory for
computing the diffraction patterns of circular apertures and slits at arbitrary
distances z from either side of the aperture (down to z = +/- 0.0003 lambda) are
presented, and numerical examples of the results are given. These results show
that the incident geometrical field is modulated by diffraction before it reaches
the aperture plane while the reflected field is spilled into the dark space. At
distances from the aperture which are large compared to the wavelength lambda
these field expressions are reduced to the usual ones specified by Fresnel's
theory. In the specific case of a diffracting half plane the numerical results
obtained were practically the same as those given by Sommerfeld's rigorous
theory. The modified theory developed in this paper is based on the explicit
assumption that the scalar theory of light cannot explain plolarization effects.
This premise is justified in Sec. 4, where it is shown that previous attempts to
do so have produced dubious results.
PMID- 27504216
TI - Priorities for Standards and Measurements to Accelerate Innovations in Nano
Electrotechnologies: Analysis of the NIST-Energetics-IEC TC 113 Survey.
AB - In 2008, the National Institute of Standards and Technology and Energetics
Incorporated collaborated with the International Electrotechnical Commission
Technical Committee 113 (IEC TC 113) on nano-electrotechnologies to survey
members of the international nanotechnologies community about priorities for
standards and measurements to accelerate innovations in nano-electrotechnologies.
In this paper, we analyze the 459 survey responses from 45 countries as one means
to begin building a consensus on a framework leading to nano-electrotechnologies
standards development by standards organizations and national measurement
institutes. The distributions of priority rankings from all 459 respondents are
such that there are perceived distinctions with statistical confidence between
the relative international priorities for the several items ranked in each of the
following five Survey category types: 1) Nano-electrotechnology Properties, 2)
Nano-electrotechnology Taxonomy: Products, 3) Nano-electrotechnology Taxonomy:
Cross-Cutting Technologies, 4) IEC General Discipline Areas, and 5) Stages of the
Linear Economic Model. The global consensus prioritizations for ranked items in
the above five category types suggest that the IEC TC 113 should focus initially
on standards and measurements for electronic and electrical properties of sensors
and fabrication tools that support performance assessments of nano-technology
enabled sub-assemblies used in energy, medical, and computer products.
PMID- 27504217
TI - Calibration of Speed Enforcement Down-The-Road Radars.
AB - We examine the measurement uncertainty associated with different methods of
calibrating the ubiquitous down-the-road (DTR) radar used in speed enforcement.
These calibration methods include the use of audio frequency sources, tuning
forks, a fifth wheel attached to the rear of the vehicle with the radar unit, and
the speedometer of the vehicle. We also provide an analysis showing the effect of
calibration uncertainty on DTR-radar speed measurement uncertainty.
PMID- 27504218
TI - High Speed Quantum Key Distribution Over Optical Fiber Network System.
AB - The National Institute of Standards and Technology (NIST) has developed a number
of complete fiber-based high-speed quantum key distribution (QKD) systems that
includes an 850 nm QKD system for a local area network (LAN), a 1310 nm QKD
system for a metropolitan area network (MAN), and a 3-node quantum network
controlled by a network manager. This paper discusses the key techniques used to
implement these systems, which include polarization recovery, noise reduction,
frequency up-conversion detection based on a periodically polled lithium nitrate
(PPLN) waveguide, custom high-speed data handling boards and quantum network
management. Using our quantum network, a QKD secured video surveillance
application has been demonstrated. Our intention is to show the feasibility and
sophistication of QKD systems based on current technology.
PMID- 27504219
TI - Method for the Characterization of Extreme-Ultraviolet Photoresist Outgassing.
AB - Outgassing from photoresists illuminated by extreme ultraviolet radiation can
lead to degradation of the very expensive multilayer-coated optics in an extreme
ultraviolet stepper. Reliable quantification of the various organic molecules
outgassed by photoresists has been a challenging goal. We have designed a compact
system for this measurement. In the first step, the total number of molecules
emitted by the photoresist is measured using a pressure-rise method in a closed
vacuum chamber, with the pressure measured by mechanical means using a
capacitance displacement gauge. To provide identification and relative
abundances, the outgassed molecules are then collected in an evacuated trap
cooled by liquid nitrogen for subsequent analysis by gas chromatography with mass
spectrometry. We will discuss the design and performance of the system.
PMID- 27504220
TI - The Detection of Lyman Alpha Radiation Formed by the Slowing Down of Protons and
Tritons Produced by the (3)He (n, tp) Reaction-A Model Study.
AB - The observation of Lyman alpha (Lalpha) radiation produced by the end products of
the (3)He (n,tp) reaction has suggested the possibility of a new method of cold
thermal neutron detection. In order for this goal to be achieved, a basic
understanding of how the Lalpha radiation is formed and how it may be detected,
is needed. The model study described here is an attempt to provide this basic
understanding and to provide quantitative results that can be used in designing
future experiments.
PMID- 27504221
TI - Pass-Fail Testing: Statistical Requirements and Interpretations.
AB - Performance standards for detector systems often include requirements for
probability of detection and probability of false alarm at a specified level of
statistical confidence. This paper reviews the accepted definitions of confidence
level and of critical value. It describes the testing requirements for
establishing either of these probabilities at a desired confidence level. These
requirements are computable in terms of functions that are readily available in
statistical software packages and general spreadsheet applications. The
statistical interpretations of the critical values are discussed. A table is
included for illustration, and a plot is presented showing the minimum required
numbers of pass-fail tests. The results given here are applicable to one-sided
testing of any system with performance characteristics conforming to a binomial
distribution.
PMID- 27504222
TI - Characterization of Probe Dynamic Behaviors in Critical Dimension Atomic Force
Microscopy.
AB - This paper describes a detailed computational model of the interaction between an
atomic force microscope probe tip and a sample surface. The model provides
analyses of dynamic behaviors of the tip to estimate the probe deflections due to
surface intermittent contact and the resulting dimensional biases and
uncertainties. Probe tip and cantilever beam responses to intermittent contact
between the probe tip and sample surface are computed using the finite element
method. Intermittent contacts with a wall and a horizontal surface are computed
and modeled, respectively. Using a 75 nm Critical Dimension (CD) tip as an
example, the responses of the probe to interaction forces between the sample
surface and the probe tip are shown in both time and frequency domains. In
particular, interaction forces between the tip and both a vertical wall and a
horizontal surface of a silicon sample are modeled using Lennard-Jones theory.
The Snap-in and Snap-out of the probe tip in surface scanning are calculated and
shown in the time domain. Based on the given tip-sample interaction force model,
the calculation includes the compliance of the probe and dynamic forces generated
by an excitation. Cantilever and probe tip deflections versus interaction forces
in the time domain can be derived for both vertical contact with a plateau and
horizontal contact with a side wall. Dynamic analysis using the finite element
method and Lennard-Jones model provide a unique means to analyze the interaction
of the probe and sample, including calculation of the deflection and the gap
between the probe tip and the measured sample surface.
PMID- 27504223
TI - Procedures for Wavelength Calibration and Spectral Response Correction of CCD
Array Spectrometers.
AB - This work describes a procedure for acquiring a spectrum of an analyte over an
extended range of wavelengths and validating the wavelength and intensity
assignments. To acquire a spectrum over an extended range of wavelengths with a
spectrometer with a charge coupled device (CCD) array detector, it is necessary
to acquire many partial spectra, each at a different angular position of the
grating, and splice the partial spectra into a single extended spectrum. The
splicing procedure exposes instrument dependent artifacts. It is demonstrated
that by taking a spectrum of a reference irradiance source and making spectral
correction, the artifacts exposed by the splicing are removed from the analyte
spectrum. This is because the irradiance reference spectrum contains the same
artifacts as the analyte spectrum. The artifacts exposed by the splicing depend
on the wavelength of the splice; therefore it is important to measure the
irradiance reference spectrum for the same range of wavelengths used to measure
the spectrum of the analyte solution. In other words, there is no general
spectral correction factor which is applicable to spectra taken for different
range of wavelengths. The wavelength calibration is also carried out by splicing
many partial spectra from a source like a krypton lamp. However the wavelength
assignments are not sensitive to the splicing procedure and the same wavelength
calibration can be used for spectra acquired over different extended wavelength
ranges. The wavelength calibration checks the validity of the setting of the
grating angular position, and the assignment of wavelengths to individual pixels
on the CCD array detector. The procedure is illustrated by measuring the spectrum
of an orange glass and the spectrum of a suspension of microalgae.
PMID- 27504224
TI - Design of the DEMO Fusion Reactor Following ITER.
AB - Runs of the NSTAB nonlinear stability code show there are many three-dimensional
(3D) solutions of the advanced tokamak problem subject to axially symmetric
boundary conditions. These numerical simulations based on mathematical equations
in conservation form predict that the ITER international tokamak project will
encounter persistent disruptions and edge localized mode (ELMS) crashes. Test
particle runs of the TRAN transport code suggest that for quasineutrality to
prevail in tokamaks a certain minimum level of 3D asymmetry of the magnetic
spectrum is required which is comparable to that found in quasiaxially symmetric
(QAS) stellarators. The computational theory suggests that a QAS stellarator with
two field periods and proportions like those of ITER is a good candidate for a
fusion reactor. For a demonstration reactor (DEMO) we seek an experiment that
combines the best features of ITER, with a system of QAS coils providing external
rotational transform, which is a measure of the poloidal field. We have
discovered a configuration with unusually good quasisymmetry that is ideal for
this task.
PMID- 27504225
TI - A Method for Assigning Priorities to United States Measurement System (USMS)
Needs: Nano-Electrotechnologies.
AB - In 2006, the National Institute of Standards and Technology conducted an
assessment of the U.S. measurement system (USMS), which encompasses all private
and public organizations that develop, supply, use, or ensure the validity of
measurement results. As part of that assessment, NIST collaborated with
Energetics Incorporated to identify and authenticate 723 measurement needs that
are barriers to technological innovations. A number of these measurement needs
(64) are relevant to accelerating innovation and commercialization of nano
electrotechnologies. In this paper, we apply the taxonomy from a 2008
international survey that established a global consensus of priorities for
standards and measurements in nano-electrotechnologies to rank in priority order
the relevant 64 USMS-identified measurement needs. This paper presents a method
for assigning priorities that is statistically based and represents a global
consensus of stakeholders. Such a method is needed because limited resources
exist to address the large number of measurement needs in nano
electrotechnologies, and the most critical measurement needs should be addressed
first.
PMID- 27504226
TI - First-Principles Calculation of the Third Virial Coefficient of Helium.
AB - Knowledge of the pair and three-body potential-energy surfaces of helium is now
sufficient to allow calculation of the third density virial coefficient, C(T),
with significantly smaller uncertainty than that of existing experimental data.
In this work, we employ the best available pair and three-body potentials for
helium and calculate C(T) with path-integral Monte Carlo (PIMC) calculations
supplemented by semiclassical calculations. The values of C(T) presented extend
from 24.5561 K to 10 000 K. In the important metrological range of temperatures
near 273.16 K, our uncertainties are smaller than the best experimental results
by approximately an order of magnitude, and the reduction in uncertainty at other
temperatures is at least as great. For convenience in calculation of C(T) and its
derivatives, a simple correlating equation is presented.
PMID- 27504227
TI - Perturbations From Ducts on the Modes of Acoustic Thermometers.
AB - We examine the perturbations of the modes of an acoustic thermometer caused by
circular ducts used either for gas flow or as acoustic waveguides coupled to
remote transducers. We calculate the acoustic admittance of circular ducts using
a model based on transmission line theory. The admittance is used to calculate
the perturbations to the resonance frequencies and half-widths of the modes of
spherical and cylindrical acoustic resonators as functions of the duct's radius,
length, and the locations of the transducers along the duct's length. To verify
the model, we measured the complex acoustic admittances of a series of circular
tubes as a function of length between 200 Hz and 10 kHz using a three-port
acoustic coupler. The absolute magnitude of the specific acoustic admittance is
approximately one. For a 1.4 mm inside-diameter, 1.4 m long tube, the root mean
square difference between the measured and modeled specific admittances (both
real and imaginary parts) over this frequency range was 0.018. We conclude by
presenting design considerations for ducts connected to acoustic thermometers.
PMID- 27504228
TI - Uncertainty Calculation for Spectral-Responsivity Measurements.
AB - This paper discusses a procedure for measuring the absolute spectral responsivity
of optical-fiber power meters and computation of the calibration uncertainty. The
procedure reconciles measurement results associated with a monochromator-based
measurement system with those obtained with laser sources coupled with optical
fiber. Relative expanded uncertainties based on the methods from the Guide to the
Expression of Uncertainty in Measurement and from Supplement 1 to the "Guide to
the Expression of Uncertainty in Measurement"-Propagation of Distributions using
a Monte Carlo Method are derived and compared. An example is used to illustrate
the procedures and calculation of uncertainties.
PMID- 27504229
TI - Calcium Fluoride Precipitation and Deposition From 12 mmol/L Fluoride Solutions
With Different Calcium Addition Rates.
AB - The effects of different Ca-addition rates on calcium fluoride (CaF2)
precipitation and deposition were investigated in 12 mmol/L sodium fluoride
solutions to which 0.1 mol/L calcium chloride solution was continuously added at
average rates of (5, 7.5, 10, 12.5, 15 or 20) mmol L(-1) min(-1). The changes in
ionic fluoride and calcium concentrations, as well as turbidity, were
continuously recorded by F and Ca electrodes, and a fiber optic based
spectrophotometer, respectively. The F(-) concentration decreased and turbidity
increased with time indicating precipitation of CaF2. For the systems with Ca
addition rates of (5, 7.5, 10, 12.5, 15, and 20) mmol L(-1) min(-1), the 1 min
CaF2 depositions in the model substrate (cellulose filter paper, pores 0.2 um)
expressed as mean +/- SD of deposited F per substrate surface area were (3.78 +/-
0.31, 11.45 +/- 0.89, 9.31 +/- 0.68, 8.20 +/- 0.56, 6.63 +/- 0.43, and 2.09 +/-
0.28) ug/cm(2), respectively (n = 10 for each group). The 1-min F depositions did
not show positive correlation to Ca-addition rates. The lowest 1-min F deposition
was obtained in the systems with the highest Ca-addition rate of 20 mmol L(-1)
min(-1) for which CaF2 precipitation rate reached the maximum value of 0.31 mmol
L(-1) s(-1) almost immediately after beginning of reaction (6 s). The largest 1
min F depositions were obtained from the systems with Ca addition rates of (7.5
to 12.5) mmol L(-1) min(-1) in which CaF2 precipitation rates continuously
increased reaching the maximum values of (0.13 to 0.20) mmol L(-1) s(-1) after
(18 to 29) s, respectively. The 1-min F depositions were greatly enhanced in
comparison with the control F solutions that did not have continuous Ca-addition.
This indicates that continuous Ca addition that controls the rate of CaF2
formation could be a critical factor for larger F depositions from F solutions.
The efficacy of conventional F mouthrinses could be improved with addition of a
substance that continuously releases Ca.
PMID- 27504230
TI - New Spherical Gamma-Ray and Neutron Emitting Sources for Testing of Radiation
Detection Instruments.
AB - The National Institute of Standards and Technology (NIST) has developed new gamma
ray and neutron emitting sources for testing radiation detection systems. These
radioactive sources were developed for testing of detection systems in maritime
applications. This required special source characteristics.
PMID- 27504231
TI - Comparison of the NIST and PTB Air-Kerma Standards for Low-Energy X-Rays.
AB - A comparison has been made of the air-kerma standards for low-energy x rays at
the National Institute of Standards and Technology (NIST) and the Physikalisch
Technische Bundesanstalt (PTB). The comparison involved a series of measurements
at the PTB and the NIST using the air-kerma standards and two NIST reference
class transfer ionization chamber standards. Results are presented for the
reference radiation beam qualities in the range from 25 kV to 50 kV for low
energy x rays, including the techniques used for mammography dose traceability.
The tungsten generated reference radiation qualities, between 25 kV and 50 kV
used for this comparison, are new to NIST; therefore this comparison will serve
as the preliminary comparison for NIST and a verification of the primary standard
correction factors. The mammography comparison will repeat two previously
unpublished comparisons between PTB and NIST. The results show the standards to
be in reasonable agreement within the standard uncertainty of the comparison of
about 0.4 %.
PMID- 27504232
TI - Elastic-Stiffness Coefficients of Titanium Diboride.
AB - Using resonance ultrasound spectroscopy, we measured the monocrystal elastic
stiffness coefficients, the Voigt C ij, of TiB2. With hexagonal symmetry, TiB2
exhibits five independent C ij: C 11, C 33, C 44, C 12, C 13. Using Voigt-Reuss
Hill averaging, we converted these monocrystal values to quasiisotropic
(polycrystal) elastic stiffnesses. Briefly, we comment on effects of voids. From
the C ij, we calculated the Debye characteristic temperature, the Gruneisen
parameter, and various sound velocities. Our study resolves the enormous
differences between two previous reports of TiB2's C ij.
PMID- 27504233
TI - DAVE: A Comprehensive Software Suite for the Reduction, Visualization, and
Analysis of Low Energy Neutron Spectroscopic Data.
AB - National user facilities such as the NIST Center for Neutron Research (NCNR)
require a significant base of software to treat the data produced by their
specialized measurement instruments. There is no universally accepted and used
data treatment package for the reduction, visualization, and analysis of
inelastic neutron scattering data. However, we believe that the software
development approach adopted at the NCNR has some key characteristics that have
resulted in a successful software package called DAVE (the Data Analysis and
Visualization Environment). It is developed using a high level scientific
programming language, and it has been widely adopted in the United States and
abroad. In this paper we describe the development approach, elements of the DAVE
software suite, its usage and impact, and future directions and opportunities for
development.
PMID- 27504236
TI - An iterative expanding and shrinking process for processor allocation in mixed
parallel workflow scheduling.
AB - Parallel computation has been widely applied in a variety of large-scale
scientific and engineering applications. Many studies indicate that exploiting
both task and data parallelisms, i.e. mixed-parallel workflows, to solve large
computational problems can get better efficacy compared with either pure task
parallelism or pure data parallelism. Scheduling traditional workflows of pure
task parallelism on parallel systems has long been known to be an NP-complete
problem. Mixed-parallel workflow scheduling has to deal with an additional
challenging issue of processor allocation. In this paper, we explore the
processor allocation issue in scheduling mixed-parallel workflows of moldable
tasks, called M-task, and propose an Iterative Allocation Expanding and Shrinking
(IAES) approach. Compared to previous approaches, our IAES has two distinguishing
features. The first is allocating more processors to the tasks on allocated
critical paths for effectively reducing the makespan of workflow execution. The
second is allowing the processor allocation of an M-task to shrink during the
iterative procedure, resulting in a more flexible and effective process for
finding better allocation. The proposed IAES approach has been evaluated with a
series of simulation experiments and compared to several well-known previous
methods, including CPR, CPA, MCPA, and MCPA2. The experimental results indicate
that our IAES approach outperforms those previous methods significantly in most
situations, especially when nodes of the same layer in a workflow might have
unequal workloads.
PMID- 27504235
TI - Health related quality of life for young people receiving dialectical behaviour
therapy (DBT): a routine outcome-monitoring pilot.
AB - PURPOSE: Adults presenting with borderline personality disorder (BPD) score
poorly on measures of health related quality of life (HRQoL). Little is known
about HRQoL in adolescents with BPD type presentations and how treatment impacts
quality of life. Our primary aim was to use routinely collected quality-of-life
outcome measures pre and post-treatment in dialectical behaviour therapy (DBT)
for adolescents to address this gap. Secondary aims were to benchmark these data
against EuroQol 5 dimensions (EQ-5DTM) outcomes for clients treated in clinical
trials and to assess the potential of the EQ-5DTM as a benchmarking tool. METHOD:
Four adolescent DBT teams, routinely collecting outcome data using a
pseudonymised secure web-based system, supplied data from consecutive discharges.
RESULTS: Young people in the DBT programmes (n = 43) had severely impaired HRQoL
scores that were lower at programme admission than those reported in published
studies using the EQ-5DTM in adults with a BPD diagnosis and in one study of
adolescents treated for depression. 40 % of adolescents treated achieved Reliable
Clinical Change. HRQoL improved between admission and discharge with a large
effect size. These results were not statistically significant when clustering in
programme outcomes was accounted for. CONCLUSION: Young people treated in NHS DBT
programmes for BPD type presentations had poorer HRQoL than adults with a BPD
diagnosis and adolescents with depression treated in published clinical trials.
The EQ-5DTM detected reliable change in this group of adolescents. Programme
outcome clustering suggests that both the measure and the web-based monitoring
system provide a mechanism for benchmarking clinical programmes.
PMID- 27504234
TI - Helping patients to reduce tobacco consumption in oncology: a narrative review.
AB - The present overview focuses on evidence of smoking cessation approaches in
oncology settings with the aim to provide health personnel a critical perspective
on how to help their patients. This narrative review is structured in two main
sections: the first one describes the psycho-cognitive variables involved in the
decision to continue smoking after a cancer diagnosis and during the treatment;
the second section relates methods and tools may be recommended, being evidence
based, to support smoking cessation in oncology settings. Active smoking
increases not only susceptibility to common cancers in the general population,
but also increases disease severity and comorbidities in cancer patients.
Nowadays, scientific evidence has identified many strategies to give up smoking,
but a lack of knowledge exists for treatment of nicotine dependence in the cancer
population. Health personnel is often ambiguous when approaching the problem,
while their contribution is essential in guiding patients towards healthier
choices. We argue that smoking treatments for cancer patients deserve more
attention and that clinical features, individual characteristics and needs of the
patient should be assessed in order to increase the attempts success rate. Health
personnel that daily work and interact with cancer patients and their caregivers
have a fundamental role in the promotion of the health changing. For this reason,
it is important that they have adequate knowledge and resources in order to
support cancer patients to stop tobacco cigarette smoking and promoting and
healthier lifestyle.
PMID- 27504237
TI - SentiHealth: creating health-related sentiment lexicon using hybrid approach.
AB - The exponential increase in the health-related online reviews has played a
pivotal role in the development of sentiment analysis systems for extracting and
analyzing user-generated health reviews about a drug or medication. The existing
general purpose opinion lexicons, such as SentiWordNet has a limited coverage of
health-related terms, creating problems for the development of health-based
sentiment analysis applications. In this work, we present a hybrid approach to
create health-related domain specific lexicon for the efficient classification
and scoring of health-related users' sentiments. The proposed approach is based
on the bootstrapping modal, a dataset of health reviews, and corpus-based
sentiment detection and scoring. In each of the iteration, vocabulary of the
lexicon is updated automatically from an initial seed cache, irrelevant words are
filtered, words are declared as medical or non-medical entries, and finally
sentiment class and score is assigned to each of the word. The results obtained
demonstrate the efficacy of the proposed technique.
PMID- 27504238
TI - Joint large deviation result for empirical measures of the coloured random
geometric graphs.
AB - We prove joint large deviation principle for the empirical pair measure and
empirical locality measure of the near intermediate coloured random geometric
graph models on n points picked uniformly in a d-dimensional torus of a unit
circumference. From this result we obtain large deviation principles for the
number of edges per vertex, the degree distribution and the proportion of
isolated vertices for the near intermediate random geometric graph models.
PMID- 27504239
TI - Contextual determinants on the meaning of the N word.
AB - Use of the word nigger is very often castigated as slurring the referent, but
this ignores the context of use. For many people the word itself is a slur no
matter what the context, and such people argue for its eradication from the
English language. Eradicationists confuse the form of the word with its frequent
use as a slur that discredits, slights, smears, stains, besmirches people of
black African descent. In this paper I discuss several occurrences of the N word
in Quentin Tarantino's film 'Pulp Fiction'. At least one is a slur. As with many
slurs, in-group usage by people who might themselves have been slurred with the
term by out-groupers, nigger is used among African Americans to express
camaraderie. Three instances of this are examined. Another instance is where
black gangster millionaire Marcellus Wallace, after handing white boxer Butch
Coolidge money to go down in the fifth round, tells him 'You're my nigger' to
which Butch replies 'Certainly appears so'. Lastly I consider the tricky
situation where a white uses the term nigger to a black friend, not as a term of
address and not as a slur either, I argue. I discuss the composition of context
and the semantics and connotations of nigger. I examine the place and function of
the uses of nigger within the context of the film, 'Pulp Fiction', to demonstrate
that the affective quality of a linguistic expression should never be judged
without taking account of its intended perlocutionary effect within the context
in which it is uttered. We see that the basic semantic content invariably
contributes to the functional (compositional) meaning, but that pragmatic input
from connotations is essential in determining the truth value of the utterance in
which nigger appears.
PMID- 27504240
TI - Improved control configuration of PWM rectifiers based on neuro-fuzzy controller.
AB - It is well-known that rectifiers are used widely in many applications required
AC/DC transformation. With technological advances, many studies are performed for
AC/DC converters and many control methods are proposed in order to improve the
performance of these rectifiers in recent years. Pulse width modulation (PWM)
based rectifiers are one of the most popular rectifier types. PWM rectifiers have
lower input current harmonics and higher power factor compared to classical diode
and thyristor rectifiers. In this study, neuro-fuzzy controller (NFC) which has
robust, nonlinear structure and do not require the mathematical model of the
system to be controlled has been proposed for PWM rectifiers. Three NFCs are used
in control scheme of proposed PWM rectifier in order to control the dq-axis
currents and DC voltage of PWM rectifier. Moreover, simulation studies are
carried out to demonstrate the performance of the proposed control scheme at
MATLAB/Simulink environment in terms of rise time, settling time, overshoot,
power factor, total harmonic distortion and power quality.
PMID- 27504241
TI - A methodology to determine the maximum value of weighted Gini-Simpson index.
AB - Weighted Gini-Simpson index is an analytical tool that promises to be widely used
concerning biological and economics applications, relative to the assessment of
diversity measured by compositional proportions of a system defined with a finite
number of elementary states characterized by positive weights. In this paper, a
current literature review on the theme is presented and the mathematical
properties of the index are outlined, focusing on the location of the maximizer
(maximum point) and evaluation of the maximum value, with emphasis in the role of
the Lagrange multiplier critical value-closely related with the harmonic mean of
the weights-which is shown to be a barrier concerning the feasibility of the
solution. Sequential procedures are presented, either backward or forward, which
are used to obtain the correct values of the maximum point coordinates, thus
allowing for the computation of the right maximum value of the index. Also, new
theoretical results are provided, such as the calculus of limits and partial
derivatives related to the critical solution, used to assess of the effectiveness
of the algorithms herein proposed and discussed.
PMID- 27504242
TI - Effects of tongue-hold swallows on suprahyoid muscle activation according to the
relative tongue protrusion length: a preliminary study.
AB - Tongue-hold swallow (THS) is a therapeutic maneuver used to increase the
posterior pharyngeal wall motion during swallowing. This maneuver has also been
reported to result in increased activation of the suprahyoid muscles. The
hypothesis of this study was that the degree of suprahyoid muscle activation
would depend on the tongue protrusion-length. The aim of this study was to
investigate the activation levels of the suprahyoid muscles by surface
electromyography (sEMG) while performing the THS maneuver at three tongue
protrusion lengths. Suprahyoid muscle activity during THSs was recorded in 25
adult volunteers (17 women and 8 men; age range 20-38 years). To record the
activity of the suprahyoid muscles while the participants performed the maneuver,
surface wireless EMG electrodes separated by a distance of 1 cm were placed on
the skin on both sides of the midline under the chin. Each activity was recorded
three times. Data analysis was performed by repeated-measures analysis of
variance. Our results revealed that participants exhibited greater electrical
activity during THS with 2/3rd or maximal tongue protrusion as compared to THS
with 1/3rd tongue protrusion (p <= 0.001). To maximize the therapeutic effect of
the THS maneuver, it is advised to protrude the tongue maximally as long as
swallowing is possible.
PMID- 27504243
TI - The valuation of currency options by fractional Brownian motion.
AB - This research aims to investigate a model for pricing of currency options in
which value governed by the fractional Brownian motion model (FBM). The
fractional partial differential equation and some Greeks are also obtained. In
addition, some properties of our pricing formula and simulation studies are
presented, which demonstrate that the FBM model is easy to use.
PMID- 27504244
TI - Low neutrophil alkaline phosphatase score is a new aspect of calreticulin-mutated
myeloproliferative neoplasms.
AB - Calreticulin (CALR) and JAK2-V617F gene mutations, which are major genetic
mutations in patients with primary myelofibrosis (PMF) and essential
thrombocythemia (ET), exert different effects on the clinical features and
outcomes of these diseases. We analyzed 88 and 9 patients with ET and PMF,
respectively, and determined the differences in the clinical characteristics of
ET patients with JAK2-V617F compared with CALR mutations. The frequency of the
JAK2-V617F and CALR mutations were 64 and 22 %, respectively. Patients with CALR
mutations were younger, had a lower white blood cell count, and had a lower rate
of thrombotic events than patients with the JAK2 mutation. The neutrophil
alkaline phosphatase (NAP) score of 16 patients with CALR mutations was
significantly lower than the normal controls, which was mainly due to the high
proportion of NAP-negative neutrophils. This is the first report to show an
association between CALR mutations in patients with myeloproliferative neoplasms
(MPN) and the NAP score. Although the mechanism is unclear, the NAP score could
be a useful and reliable biochemical marker to discriminate the mutational status
of MPN patients. Further investigation is warranted to determine whether these
characteristics contribute to the pathogenesis of MPN and the NAP score.
PMID- 27504245
TI - Fabrication and vibration characterization of curcumin extracted from turmeric
(Curcuma longa) rhizomes of the northern Vietnam.
AB - In this report, we present the research results on using the conventional method
and microwave technology to extract curcuminoid from turmeric roots originated in
different regions of Northern Vietnam. This method is simple, yet economical, non
toxic and still able to achieve high extraction performance to get curcuminoid
from turmeric roots. The detailed results on the Raman vibration spectra combined
with X-ray powder diffraction and high-performance liquid chromatography/mass
spectrometry allowed the evaluation of each batch of curcumin crystalline powder
sample received, under the conditions of applied fabrication technology. Also,
the absorption and fluorescence spectroscopies of the samples are presented in
the paper. The information to be presented in this paper: absorption and
fluorescence spectroscopies of the samples; new experimental study results on
applied technology to mass-produce curcumin from turmeric rhizomes; comparative
study results between fabricated samples and marketing curcumin products-to state
the complexity of co-existing crystalline phase in curcumin powder samples. We
noticed that, it is possible to use the vibration line at ~959 cm(-1)
characteristic of the nu C=O vibration, and the ~1625 cm(-1) line-characteristic
of the nu C=O and nu C=C vibration in curcumin molecules, for preliminary quality
assessment of naturally originated curcumin crystalline powder samples. Data on
these new optical spectra will contribute to the bringing of detailed information
on natural curcumin in Vietnam, serving research purposes and applications of
natural curcumin powder and nanocurcumin in Vietnam, as well as being initial
materials for the pharmaceutical, cosmetics or functional food industries.
PMID- 27504246
TI - Efficacy and safety of mini percutaneous nephrolithotomy in obese patients.
AB - PURPOSE: We aimed to evaluate the effect of obesity on surgical outcomes of mini
percutaneous nephrolithotomy (Mini-PNL). METHODS: Hundred and eighty two Mini-PNL
procedures were performed between May 2013 and January 2015 and their results
were evaluated retrospectively. Patients were classified as non-obese (BMI, 18.5
30 kg/m(2)) and obese (>=30 kg/m(2)) groups. Obese and non-obese patients were
compared according to pre-operative demographic values, intra-operative surgery
techniques and post-operative results. RESULTS: BMI values of 133 patients were
lower than 30 kg/m(2) while 49 patient's BMI values were higher than 30 kg/m(2).
There were no significant difference between operation time, fluoroscopy time,
number of access and access sites when two groups were compared. No significant
difference was found in total length of hospital stay, hemoglobin drop, and
complication rates. Stone-free rates were 70.7 % in the non-obese and 71.4 % in
the obese group (p = 0.9). CONCLUSIONS: Mini-PNL procedure is a safe and
effective treatment modality, which should be strongly considered for obese
patients with appropriate sized stones.
PMID- 27504247
TI - Numerical solution of the one-dimensional fractional convection diffusion
equations based on Chebyshev operational matrix.
AB - In this paper, we are concerned with nonlinear one-dimensional fractional
convection diffusion equations. An effective approach based on Chebyshev
operational matrix is constructed to obtain the numerical solution of fractional
convection diffusion equations with variable coefficients. The principal
characteristic of the approach is the new orthogonal functions based on Chebyshev
polynomials to the fractional calculus. The corresponding fractional differential
operational matrix is derived. Then the matrix with the Tau method is utilized to
transform the solution of this problem into the solution of a system of linear
algebraic equations. By solving the linear algebraic equations, the numerical
solution is obtained. The approach is tested via examples. It is shown that the
proposed algorithm yields better results. Finally, error analysis shows that the
algorithm is convergent.
PMID- 27504248
TI - Lane changing trajectory planning and tracking control for intelligent vehicle on
curved road.
AB - This paper explores lane changing trajectory planning and tracking control for
intelligent vehicle on curved road. A novel arcs trajectory is planned for the
desired lane changing trajectory. A kinematic controller and a dynamics
controller are designed to implement the trajectory tracking control. Firstly,
the kinematic model and dynamics model of intelligent vehicle with non-holonomic
constraint are established. Secondly, two constraints of lane changing on curved
road in practice (LCCP) are proposed. Thirdly, two arcs with same curvature are
constructed for the desired lane changing trajectory. According to the
geometrical characteristics of arcs trajectory, equations of desired state can be
calculated. Finally, the backstepping method is employed to design a kinematic
trajectory tracking controller. Then the sliding-mode dynamics controller is
designed to ensure that the motion of the intelligent vehicle can follow the
desired velocity generated by kinematic controller. The stability of control
system is proved by Lyapunov theory. Computer simulation demonstrates that the
desired arcs trajectory and state curves with B-spline optimization can meet the
requirements of LCCP constraints and the proposed control schemes can make
tracking errors to converge uniformly.
PMID- 27504249
TI - The efficacy, safety, and tolerability of ivermectin compared with current
topical treatments for the inflammatory lesions of rosacea: a network meta
analysis.
AB - BACKGROUND: Rosacea is a common chronic skin condition that manifests as
recurrent inflammatory lesions. Long-term treatment is required to control
symptoms and disease progression, with topical treatments being the first-line
choice. Ivermectin 1 % cream is a new once-daily (QD) topical treatment for the
inflammatory lesions of rosacea, and it is important to compare the efficacy,
safety, and tolerability of ivermectin with other currently available topical
treatments. METHODS: A systematic literature review was performed from January
2011 to June 2015, with articles published prior to 2011 retrieved from a
Cochrane review on rosacea. Randomized controlled trials of the topical treatment
of adult patients with moderate-to-severe papulopustular rosacea were identified
from electronic databases and trial registers, and supplemented with data from
clinical study reports. Mixed treatment comparisons (MTCs) were conducted to
compare different treatments according to Bayesian methodology. RESULTS: 57
studies were identified, with 19 providing data suitable for MTC. Ivermectin 1 %
cream QD led to a significantly greater likelihood of success compared with
azelaic acid 15 % gel twice-daily (BID) [relative risk (95 % credible interval):
1.25 (1.14-1.37)], and metronidazole 0.75 % cream BID [1.17 (1.08-1.29)] at 12
weeks. Ivermectin 1 % cream QD also demonstrated a significant reduction in
inflammatory lesion count compared with azelaic acid 15 % gel BID [-8.04 (-12.69
to -3.43)] and metronidazole 0.75 % cream BID [-9.92 (-13.58 to -6.35)] at 12
weeks. Ivermectin 1 % cream QD led to a significantly lower risk of developing
any AE or TRAE compared with azelaic acid 15 % gel BID [0.83 (0.71-0.97) and 0.47
(0.32-0.67), respectively]. CONCLUSIONS: Ivermectin 1 % cream QD appears to be a
more effective topical treatment than other current options for the inflammatory
lesions of rosacea, with at least an equivalent safety and tolerability profile,
and could provide physicians and dermatologists with an alternative first-line
treatment option.
PMID- 27504250
TI - An efficient identification strategy of clonal tea cultivars using long-core
motif SSR markers.
AB - Microsatellites, or simple sequence repeats (SSRs), especially those with long
core motifs (tri-, tetra-, penta-, and hexa-nucleotide) represent an excellent
tool for DNA fingerprinting. SSRs with long-core motifs are preferred since
neighbor alleles are more easily separated and identified from each other, which
render the interpretation of electropherograms and the true alleles more
reliable. In the present work, with the purpose of characterizing a set of core
SSR markers with long-core motifs for well fingerprinting clonal cultivars of tea
(Camellia sinensis), we analyzed 66 elite clonal tea cultivars in China with 33
initially-chosen long-core motif SSR markers covering all the 15 linkage groups
of tea plant genome. A set of 6 SSR markers were conclusively selected as core
SSR markers after further selection. The polymorphic information content (PIC) of
the core SSR markers was >0.5, with <=5 alleles in each marker containing 10 or
fewer genotypes. Phylogenetic analysis revealed that the core SSR markers were
not strongly correlated with the trait 'cultivar processing-property'. The
combined probability of identity (PID) between two random cultivars for the whole
set of 6 SSR markers was estimated to be 2.22 * 10(-5), which was quite low,
confirmed the usefulness of the proposed SSR markers for fingerprinting analyses
in Camellia sinensis. Moreover, for the sake of quickly discriminating the clonal
tea cultivars, a cultivar identification diagram (CID) was subsequently
established using these core markers, which fully reflected the identification
process and provided the immediate information about which SSR markers were
needed to identify a cultivar chosen among the tested ones. The results suggested
that long-core motif SSR markers used in the investigation contributed to the
accurate and efficient identification of the clonal tea cultivars and enabled the
protection of intellectual property.
PMID- 27504251
TI - Measuring serum matrix metalloproteinase-9 levels in peripheral blood after
subarachnoid hemorrhage to predict cerebral vasospasm.
AB - PURPOSE: We aimed to investigate serum levels of matrix metalloproteinase-9 in
both subarachnoid hemorrhage and control groups for prediction of cerebral
vasospasm in this study. METHODS: Venous serum matrix metalloproteinase-9 levels
were prospectively measured four times (days 1, 3, 7, and 14) for 34 consecutive
patients with subarachnoidal hemorrhage (n = 27) and for elective aneurysm
clipping (control, n = 7). RESULTS: Vasospasm developed in 11/34 (32.4 %)
patients between 3 and 10 days after subarachnoid hemorrhage (median 5.58 days),
mean peak serum matrix metalloproteinase-9 compared with the non-vasospasm
cohort. Matrix metalloproteinase-9 levels were higher in subarachnoid hemorrhage
patients than in the controls. CONCLUSION: Increased serum matrix
metalloproteinase-9 could be an accurate biomarker to predict the onset of
cerebral vasospasm after subarachnoid hemorrhage.
PMID- 27504252
TI - Disruptive behavior among elementary students in physical education.
AB - The aim of this study was to determine which disruptive behaviors occur most
often in physical education (PE) classes, and to identify the existence of a
pattern of behavior that leads to this disruptive behavior. With this in mind, we
analyzed five PE sessions taken by pupils at different elementary school in the
region of Murcia. The total sample size was 96 students aged between 10 and 13.
Data was recorded using an observation instrument (a combination of a field
format and a categorical system) and was then analyzed using the "HOISAN"
software tool, with a sequential analysis and polar coordinates being conducted.
The results of the study revealed that disruptive behaviors (52 %) occur more
frequently than non-relevant behaviors (48 %), the most common of them being
disinterested behavior (29 %), followed by indiscipline (15 %), with no
statistically significant differences being detected in violent behavior. As
regards patterns of behavior, disinterested behavior is stimulated by "no eye
contact", "middle distance", "inside the task", "no use of material", "giving
orders" and "registering of activities", while indiscipline is stimulated by "no
eye contact", "far distance", "outside the task", "use of material", "grouping in
pairs" and "preparation of material". In conclusion, it can be stated that
disruptiveness is far more common in physical education sessions, affects the
development of sessions and has a negative impact on student learning. A solution
to this problem should therefore be sought immediately in order to ensure quality
education.
PMID- 27504253
TI - Development of a new testing equipment that combines the working principles of
both the split Hopkinson bar and the drop weight testers.
AB - In the current work, a new high strain rate tensile testing equipment is
proposed. The equipment uses a pendulum device to generate an impact load and a
three-bar mechanism to bring that load to act upon a specially designed specimen.
As the standard impact testing apparatus uses pendulum device and the well-known
SHB high strain rate tester adopts the above-mentioned mechanism, the introduced
equipment can be dealt with as an impact apparatus in which the base that
supports the V-shape specimen is replaced with the three-bar configuration that
the traditional SHB uses. In order to demonstrate the applicability of the new
tester, virtual design tools were used to determine the most appropriate
configuration for it. Then, a detailed design was created, and a full-scale
prototype was produced, calibrated, instrumented and tested. The obtained results
demonstrate that the new tester is capable of axially straining steel specimens
up to failure at a maximum rate of about 250 s(-1), which is reasonable when
compared with a more established high strain rate testers.
PMID- 27504254
TI - Impact of pipelines on land use in rural areas in Turkey.
AB - This paper examines whether the parcelization of land through easement as a
result of the construction of pipelines in rural areas in Turkey has any negative
effects on productive land use. The current legislation in Turkey does not allow
the division of land in most rural areas into parcels smaller than 5000 m(2).
Therefore, the smallest parcel that can be productively used was considered as
5000 m(2). On the basis of the analysis of the data pertaining to the easement
rights having two different widths and collected from three different regions
having different parcel sizes, the research aims to find out the number of
parcels with an area less than 5000 m(2) (excluding the easement) that were
created by the construction of pipelines and to investigate whether a significant
number of areas less than 5000 m(2) remain. This study also demonstrates a method
that can be used in studies on this subject according to the various parcel sizes
that were created by the allotment of parcels due to the easement of the
construction of pipelines.
PMID- 27504255
TI - The qualitative and quantitative analysis of the coupled C, N, P and Si retention
in complex of water reservoirs.
AB - The Solina-Myczkowce complex of reservoirs (SMCR) accounts about 15 % of the
water storage in Poland. On the base of historical (2004-2006 years) data, the
mass balance of nitrogen, phosphorus, total organic carbon and dissolved silicon
were calculated. Large, natural affluents were the main source of the biogenic
compounds in the studied ecosystem, delivering 90 % of TOC, 87 % of TN and 81 %
of TP and DSi load. Moreover, results show that SMCR is an important sink for all
the analysed biogenic elements. About 15-30 % of external loads were retained in
the reservoir mainly in upper Solina. Due to the intensive processes of primary
production, inorganic forms of nitrogen and phosphorus were mainly retained.
Internal production of organic matter lead to an amount of the organic matter
deposited in the sediments greater than was anticipated on the basis of the mass
balance calculations. A constant load of dissolved silicon originating only from
natural sources did not contribute to supplement deficits of Si present in the
body of water in the reservoirs, promoting disturbances in N:C:P:Si ratios and
another growth condition for other types of algae.
PMID- 27504256
TI - Effect of vertically aligned carbon nanotube density on the water flux and salt
rejection in desalination membranes.
AB - In this paper, vertically aligned carbon nanotube (VACNT) membranes of different
densities are developed and their performances are investigated. VACNT arrays of
densities 5 * 10(9), 10(10), 5 * 10(10) and 10(11) tubes cm(-2), are initially
grown on 1 cm * 1 cm silicon substrates using chemical vapour deposition. A VACNT
membrane is realised by attaching a 300 MUm-thick 1 cm * 1 cm VACNT array on
silicon to a 4" glass substrate, applying polydimethylsiloxane (PDMS) through
spin coating to fill the gaps between the VACNTs, and using a microtome to slice
the VACNT-PDMS composite into 25-MUm-thick membranes. Experimental results show
that the permeability of the developed VACNT membranes increases with the density
of the VACNTs, while the salt rejection is almost independent of the VACNT
density. The best measured permeance is attained with a VACNT membrane having a
CNT density of 10(11) tubes cm(-2) is 1203 LMH at 1 bar.
PMID- 27504257
TI - Exploring the nature of science through courage and purpose: a case study of
Nikolai Vavilov and plant biodiversity.
AB - INTRODUCTION: Historical biographies facilitate teaching the 'nature of science'.
This case study focuses on how Nikolai Vavilov's unrelenting sense of purpose,
courage, and charismatic personality was maintained during violent revolutionary
change in Russia. CASE DESCRIPTION: The rediscovery of Gregor Mendel's laws of
inheritance provided Vavilov with a scientific foundation for crop improvement,
this foundation was later bolstered by Vavilov's personal drive to conserve plant
biodiversity. As he advanced theories and pragmatic approaches for genetic
improvement and conservation of plants, political leaders in Russian came to
reject Mendel's principles and eventually Vavilov's work. DISCUSSION AND
EVALUATION: This rejection occurred because Joseph Stalin was desperate for a
quick remedy to the famine and suffering from forced collective agriculture.
Vavilov's work continued, modernizing Russian crop research while inspiring other
scientists to save seeds stored in the world's first gene bank. Three themes
illustrating the nature of science help examine Vavilov's life: explaining
natural phenomena, uncompromising human endeavor, and revising scientific
knowledge. CONCLUSIONS: The case study concludes with four questions to stimulate
student inquiry and self-guided research. They also deepen student understanding
of Vavilov's personal sacrifices to ensure use and conservation of plant
biodiversity.
PMID- 27504258
TI - Kinetics, equilibrium, and thermodynamics investigation on the adsorption of
lead(II) by coal-based activated carbon.
AB - The goal of this research is to investigate the feasibility of using activated
coal-based activated carbon (CBAC) to adsorb Pb(II) from aqueous solutions
through batch tests. Effects of contact time, pH, temperature and initial Pb(II)
concentration on the Pb(II) adsorption were examined. The Pb(II) adsorption is
strongly dependent on pH, but insensitive to temperature. The best pH for Pb(II)
removal is in the range of 5.0-5.5 with more than 90 % of Pb(II) removed. The
equilibrium time was found to be 60 min and the adsorption data followed the
pseudo-second-order kinetics. Isotherm data followed Langmuir isotherm model with
a maximum adsorption capacity of 162.33 mg/g. The adsorption was exothermic and
spontaneous in nature. The Fourier transform infrared spectroscopy and scanning
electron microscopy analysis suggested that CBAC possessed a porous structure and
was rich in carboxyl and hydroxyl groups on its surface, which might play a major
role in Pb(II) adsorption. These findings indicated that CBAC has great potential
as an alternative adsorbent for Pb(II) removal.
PMID- 27504259
TI - Constitutive expression of genes encoding notch receptors and ligands in
developing lymphocytes, nTreg cells and dendritic cells in the human thymus.
AB - The thymus is the site of T cell maturation. Notch receptors (Notch1-4) and
ligands (DLL1-3 and Jagged1-2) constitute one of several pathways involved in
this process. Our data revealed differential constitutive expression of Notch
genes and ligands in T lymphocytes and thymic dendritic cells (tDCs), suggesting
their participation in human thymocyte maturation. nTreg analyses indicated that
the Notch components function in parallel to promote maturation in the thymus.
PMID- 27504260
TI - De novo assembly of the blunt snout bream (Megalobrama amblycephala) gill
transcriptome to identify ammonia exposure associated microRNAs and their
targets.
AB - De novo transcriptome sequencing is a robust method for microRNA (miRNA) target
gene prediction, especially for organisms without reference genomes. Following
exposure of Megalobrama amblycephala to ammonia (0.1 or 20 mg L(-1) ), two cDNA
libraries were constructed from the fish gills and sequenced using Illumina HiSeq
2000. Over 90 million reads were generated and de novo assembled into 46, 615
unigenes, which were then extensively annotated by comparing to different protein
databases, followed by biochemical pathway prediction. The expression of 2666
unigenes significantly differed; 1961 were up-regulated, while 975 were down
regulated. Among these, 250 unigenes were identified as the targets for 10
conserved and 4 putative novel miRNA families by miRNA target computational
prediction. We examined expression of ssa-miRNA-21 and its target genes by real
time quantitative PCR and found agreement with the sequencing data. This study
demonstrates the feasibility of identifying miRNA targets by transcriptome
analysis. The transcriptome assembly data represent a substantial increase in the
genomic resources available for Megalobrama amblycephala and will be useful for
gene expression profile analysis and miRNA functional annotation.
PMID- 27504261
TI - Disrupted functional connectivity in adolescent obesity.
AB - BACKGROUND/OBJECTIVE: Obesity has been associated with brain alterations
characterised by poorer interaction between a hypersensitive reward system and a
comparatively weaker prefrontal-cognitive control system. These alterations may
occur as early as in adolescence, but this notion remains unclear, as no studies
so far have examined global functional connectivity in adolescents with excess
weight. SUBJECTS/METHODS: We investigated functional connectivity in a sample of
60 adolescents with excess weight and 55 normal weight controls. We first
identified parts of the brain displaying between-group global connectivity
differences and then characterised the extent of the differences in functional
network integrity and their association with reward sensitivity. RESULTS:
Adolescent obesity was linked to neuroadaptations in functional connectivity
within brain hubs linked to interoception (insula), emotional memory (middle
temporal gyrus) and cognitive control (dorsolateral prefrontal cortex) (pFWE <
0.05). The connectivity between the insula and the anterior cingulate cortex was
reduced in comparison to controls, as was the connectivity between the middle
temporal gyrus and the posterior cingulate cortex and cuneus/precuneus (pFWE <
0.05). Conversely, the middle temporal gyrus displayed increased connectivity
with the orbitofrontal cortex (pFWE < 0.05). Critically, these networks were
correlated with sensitivity to reward (p < 0.05). CONCLUSIONS: These findings
suggest that adolescent obesity is linked to disrupted functional connectivity in
brain networks relevant to maintaining balance between reward, emotional memories
and cognitive control. Our findings may contribute to reconceptualization of
obesity as a multi-layered brain disorder leading to compromised motivation and
control, and provide a biological account to target prevention strategies for
adolescent obesity.
PMID- 27504263
TI - Wolf-Hirschhorn (4p-) syndrome with West syndrome.
AB - Wolf-Hirschhorn syndrome (WHS) is a chromosome disorder (4p-syndrome) which is
characterized by craniofacial features and epileptic seizures. Here, we report a
case of WHS with West syndrome, in whom the seizures were refractory to several
antiepileptic drugs but were responsive to the addition of lamotrigine. The
patient had epileptic spasms at age seven months. The interictal
electroencephalogram was hypsarrhythmic. After adding lamotrigine, seizures
decreased remarkably, and spasms disappeared. We have identified and described
the very rare case of a girl with WHS who also developed West syndrome. In this
case, adding lamotrigine to her medications effectively treated the spasms.
PMID- 27504262
TI - Associations of limbic-affective brain activity and severity of ongoing chronic
arthritis pain are explained by trait anxiety.
AB - Functional magnetic resonance imaging studies (fMRI) have transformed our
understanding of central processing of evoked pain but the typically used block
and event-related designs are not best suited to the study of ongoing pain. Here
we used arterial spin labelling (ASL) for cerebral blood flow mapping to
characterise the neural correlates of perceived intensity of osteoarthritis (OA)
pain and its interrelation with negative affect. Twenty-six patients with painful
knee OA and twenty-seven healthy controls underwent pain phenotyping and ASL MRI
at 3T. Intensity of OA pain correlated positively with blood flow in the anterior
mid-cingulate cortex (aMCC), subgenual cingulate cortex (sgACC), bilateral
hippocampi, bilateral amygdala, left central operculum, mid-insula, putamen and
the brainstem. Additional control for trait anxiety scores reduced the pain-CBF
association to the aMCC, whilst pain catastrophizing scores only explained some
of the limbic correlations. In conclusion, we found that neural correlates of
reported intensity of ongoing chronic pain intensity mapped to limbic-affective
circuits, and that the association pattern apart from aMCC was explained by trait
anxiety thus highlighting the importance of aversiveness in the experience of
clinical pain.
PMID- 27504264
TI - Atypical benign partial epilepsy of childhood with acquired neurocognitive,
lexical semantic, and autistic spectrum disorder.
AB - Atypical benign partial epilepsy (ABPE) of childhood or pseudo-Lennox syndrome is
a form of idiopathic focal epilepsy characterized by multiple seizure types,
focal and/or generalized epileptiform discharges, continuous spike-wave during
sleep (CSWS), and sometimes reversible neurocognitive deficits. There are few
reported cases of ABPE describing detailed correlative longitudinal follow-up of
the various associated neurocognitive, language, social communicative, or motor
deficits, in parallel with the epilepsy. Furthermore, the molecular inheritance
pattern for ABPE and the wider spectrum of epilepsy aphasia disorders have yet to
be fully elucidated. We describe the phenotype-genotype study of a boy with ABPE
with follow-up from ages 5 to 13 years showing acquired oromotor and, later, a
specific lexical semantic and pervasive developmental disorder. Exome sequencing
identified variants in SCN9A, CPA6, and SCNM1. A direct role of the epilepsy in
the pathogenesis of the oromotor and neurocognitive deficits is apparent.
PMID- 27504265
TI - Towards the development of an enzyme replacement therapy for the metabolic
disorder propionic acidemia.
AB - Propionic acidemia (PA) is a life-threatening disease caused by the deficiency of
a mitochondrial biotin-dependent enzyme known as propionyl coenzyme-A carboxylase
(PCC). This enzyme is responsible for degrading the metabolic intermediate,
propionyl coenzyme-A (PP-CoA), derived from multiple metabolic pathways.
Currently, except for drastic surgical and dietary intervention that can only
provide partial symptomatic relief, no other form of therapeutic option is
available for this genetic disorder. Here, we examine a novel approach in protein
delivery by specifically targeting and localizing our protein candidate of
interest into the mitochondrial matrix of the cells. In order to test this
concept of delivery, we have utilized cell penetrating peptides (CPPs) and
mitochondria targeting sequences (MTS) to form specific fusion PCC protein,
capable of translocating and localizing across cell membranes. In vitro delivery
of our candidate fusion proteins, evaluated by confocal images and enzymatic
activity assay, indicated effectiveness of this strategy. Therefore, it holds
immense potential in creating a new paradigm in site-specific protein delivery
and enzyme replacement therapeutic for PA.
PMID- 27504266
TI - Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma
reveals a phenotypic spectrum.
AB - Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal recessive
neurometabolic disorder that presents with a broad-spectrum of neurological and
physiological symptoms. The ADSL gene produces an enzyme with binary molecular
roles in de novo purine synthesis and purine nucleotide recycling. The
biochemical phenotype of ADSL deficiency, accumulation of SAICAr and
succinyladenosine (S-Ado) in biofluids of affected individuals, serves as the
traditional target for diagnosis with targeted quantitative urine purine analysis
employed as the predominate method of detection. In this study, we report the
diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic
profiling, an analytical scheme capable of generating semi-quantitative z-score
values for over 1000 unique compounds in a single analysis of a specimen. Using
this method to analyze plasma, we diagnosed ADSL deficiency in four patients and
confirmed these findings with targeted quantitative biochemical analysis and
molecular genetic testing. ADSL deficiency is part of a large a group of
neurometabolic disorders, with a wide range of severity and sharing a broad
differential diagnosis. This phenotypic similarity among these many inborn errors
of metabolism (IEMs) has classically stood as a hurdle in their initial diagnosis
and subsequent treatment. The findings presented here demonstrate the clinical
utility of metabolomic profiling in the diagnosis of ADSL deficiency and
highlights the potential of this technology in the diagnostic evaluation of
individuals with neurologic phenotypes.
PMID- 27504267
TI - A simple, low cost GC/MS method for the sub-nanogram per litre measurement of
organotins in coastal water.
AB - Tributyltin (TBT) is a legacy pollutant in the aquatic environment, predominantly
from its use in anti-foulant paints and is listed as a priority hazardous
substance in the European Union's Water Framework Directive (WFD). Measuring low
concentrations of TBT and other organotins (e.g. monobutyltin (MBT), dibutyltin
(DBT), diphenyltin (DPhT) and triphenyltin (TPhT)) at sub ng/L concentrations in
coastal waters using standard laboratory instrumentation is very challenging.
Conventional, low injection volume gas chromatography/mass spectrometry (GC/MS)
combined with liquid-liquid extraction typically achieves limits of detection for
TBT ~10 ng L(-1). We describe a simple, programmed temperature vaporisation-large
injection volume (50 MUL), GC/MS selected ion monitoring method for measuring
DBT, TBT, DPhT and TPhT in coastal waters at lower concentrations. Quantification
of MBT was not possible using these injection volumes but was achieved using a 10
MUL injection volume together with a reduced injection speed. This new approach
offers: *When using a 50 MUL injection, limits of detection = 0.70 ng L(-1) and
limits of quantification = 2.1 ng L(-1) for TBT were achieved in derivatised
standards.*Recoveries of TBT and TPhT from coastal water >97%.*Time consuming,
off-line sample pre-concentration methods are unnecessary.
PMID- 27504268
TI - Hedgehog Signalling in the Embryonic Mouse Thymus.
AB - T cells develop in the thymus, which provides an essential environment for T cell
fate specification, and for the differentiation of multipotent progenitor cells
into major histocompatibility complex (MHC)-restricted, non-autoreactive T cells.
Here we review the role of the Hedgehog signalling pathway in T cell development,
thymic epithelial cell (TEC) development, and thymocyte-TEC cross-talk in the
embryonic mouse thymus during the last week of gestation.
PMID- 27504269
TI - Incidence of Foramen of Huschke in South Andhra Population of India.
AB - INTRODUCTION: Foramen of Huschke (FH) is an opening present in anteroinferior
wall of External Acoustic Meatus (EAM) on the tympanic plate of temporal bone.
The developing tympanic ring normally gets closed by the age of 5 years, if not,
leads to the persistence of FH, shows a communication between the EAM and
mandibular fossa of temporal bone. AIM: The aim of the present study was to
report on the incidence of FH in adult skulls and individual temporal bones,
belonging to South Coastal Andhra population. MATERIALS AND METHODS: Ninety three
skulls and 34 temporal bones (18 right and 16 left) obtained from the Department
of Anatomy and ENT respectively, irrespective of their sex were utilized. This
Tympanic Plates (TP) was observed for the occurrence of FH. RESULTS: Incidence of
FH was found in 18 (16.22%) on right and 24 (22.02%) on left side. Bilateral FH
was seen in 13 (13.98%) and multiple FH was 13 (5.91%). Mostly it was situated on
left than the right side. CONCLUSION: This study revealed that about 38% of South
Coastal Andhra crania have FH. The presence of FH may render external and middle
ear structures vulnerable to injury during arthroscopy of the Temporomandibular
Joint (TMJ). Since FH can result in TMJ herniation and salivary gland
fistulisation through the anterior wall of the bony EAM, surgeons working in this
area must be cautious during surgical procedures. Also, data obtained from
different populations, as observed from our study can be useful in racial and
anthropological studies.
PMID- 27504270
TI - Cadaveric Study on Morphology of Dorsal Interossei of Hand and its Anatomical
Variation.
AB - INTRODUCTION: The dorsal interossei are the abductors of the fingers and the
knowledge of its variation help the surgeon in treatment of fractures, claw hand
and compartment syndromes. AIM: To note the origin, insertion, pattern of muscle
fibres and tendon length of all the dorsal interossei of hand. MATERIALS AND
METHODS: Routinely dissected 30 formalin fixed hand in the Department of Anatomy,
KMC, Manipal, were observed for origin, insertion and tendon length and muscle
pattern of dorsal interossei. RESULTS: Out of 30 hands, presence of supernumerary
muscle was observed in three hands. Presence of three heads of dorsal interossei
was noted in one hand. CONCLUSION: The finding of present study is of importance
to surgeons and orthopaedicians during conservative and surgical management of
hand deformity. Adequate knowledge of these muscular variations is also important
in treatment of fractures, stiff hand, claw hand or tendon transfer.
PMID- 27504271
TI - Cadaveric Study of Berretini Communications in North Indian Population.
AB - INTRODUCTION: Intercommunication between peripheral nerves deserves special
attention in view of their clinical significance. Superficial palmar
communication between the median nerve and ulnar nerve is referred to as
Berrettini Anastomosis. The presence or absence of this communicating branch
varies between individuals. Earlier, incidence of Berretini communication
reported varied significantly (4-94%). AIM: The aim of this study was to find out
the frequency with which Berretini communication is found in North Indians.
MATERIALS AND METHODS: The present study was conducted on 60 upper limbs of 30
cadavers at the Government Medical College, Amritsar. The whole course of the
median nerve and the ulnar nerve was exposed. Communicating rami in the hand were
identified, cleaned and photographed. RESULTS: In all the six (10%) variant
limbs, the communicating branch originated from lateral common palmar digital
branch of ulnar nerve and joined medial common palmar digital branch of median
nerve. Single communication with oblique course was seen in all the variants.
Further, its ontogeny and clinical implications have been discussed in detail.
CONCLUSION: The Berretini anastomosis was seen in 10% upper limbs of the present
study. Damage to the communicating branch or the severing of the branch might
result in sensory loss which may be difficult to diagnose owing to the large
number of variations in the origin of the communicating branch. The patterns of
sensory impairment may vary depending upon the branch of median and ulnar nerve
it is seen connecting.
PMID- 27504272
TI - Unusual Origin of a Double Upper Subscapular Nerve from the Suprascapular Nerve
and the Posterior Division of the Upper Trunk of the Brachial Plexus: A Case
Report.
AB - A double upper subscapular nerve on the right side was detected in a male
cadaver, with the proximal one arising from the suprascapular nerve and the
distal one from the posterior division of the upper trunk of the brachial plexus.
Both of them penetrated and supplied the uppermost portion of the right
subscapularis muscle. That anatomic variation was associated with a median nerve
formed by two lateral roots. The origin and pattern of the upper subscapular
nerve displays high variability, however the presented combination of the
variable origin of a double upper subscapular nerve has rarely been described in
the literature. The knowledge of such an anatomic variation is essential for the
surgeon operating in the region especially in instances of brachial plexus'
repair after any traumatic injury. Moreover, the awareness of the precise origin
and topography of these nerves is important for the physician attempting to block
these nerves or utilizing these nerves as grafts for neurotization of adjacent
damaged nerves of the brachial plexus.
PMID- 27504273
TI - Looped and Tortuous Ulnar Artery - An Erratic Unilateral Vascular Presentation in
the Proximal Forearm.
AB - Precise and detailed knowledge of possible anatomical variations of the arterial
pattern in the upper extremity is vital during reparative surgery in this region.
Scientific literatures witnessed several reports on variant origin and branching
pattern of ulnar artery. But report on looped and tortuous ulnar artery is
lacking in the literature. We report here a unique case of ulnar artery having
double loop at its commencement giving it an appearance of sigmoid shape and its
undue tortuous course in the forearm. Such an unusual and unpredictable variation
of ulnar artery is vulnerable for life threatening hemorrhage during clinical
approaches. It could also lead to misinterpretation of CT scans as presence of
tumours. Awareness on such exceptional anatomical discrepancy of ulnar artery is
important to clinicians, neuroradiologists and radiologists in general.
PMID- 27504274
TI - Unusual Variation in the Branching Pattern of the Celiac Trunk and Its
Embryological and Clinical Perspective.
AB - Knowledge of variations in the branching pattern of Celiac Trunk (CT) is
important for surgeries of stomach, duodenum, pancreas and hepatobiliary region,
for abdominal aortic aneurysm, for liver transplant and chaemoembolization of
hepatic tumours. An unusual variation in the branching pattern of CT was observed
in 50-year-old male cadaver of Indian origin. CT divided into six branches out of
which right & left inferior phrenic arteries originated as first two branches and
left gastric artery as the third branch. CT ended into three terminal branches as
common hepatic artery, splenic artery & dorsal pancreatic artery. Right gastric
artery originated from left hepatic artery instead of common hepatic artery. A
variant hepatic artery to the left lobe of liver was also observed which
originated from right gastric artery. Anatomical variations in the branching
pattern of CT are due to developmental changes in ventral splanchnic artery.
PMID- 27504275
TI - Comparison of Oxidative Stress Markers and Serum Cortisol between Normal Labor
and Selective Cesarean Section Born Neonates.
AB - INTRODUCTION: An imbalance between antioxidant and oxidant-generating systems in
newborns can cause oxidative damage. The effect of modes of delivery on oxidative
stress in neonates is not fully investigated. AIM: This study was aimed to
examine the effects of modes of delivery on oxidative stress markers and cortisol
in newborns. MATERIALS AND METHODS: In this study 60 term neonates {30 born via
Normal Delivery (ND) and 30 born via elective Caesarean Delivery (CS)} at birth
were enrolled. Glutathione Peroxidase (GPx), Catalase (CAT) and Superoxide
Dismutase (SOD) activities were determined in umbilical cord blood in all
neonates. Moreover serum cortisol, uric acid and Total Antioxidant Capacity (TAC)
were measured. RESULTS: GPx and SOD activities in cesarean born neonates were
significantly higher than those of control subjects (p<0.05). TAC and CAT were
not significantly different between the two groups. Serum cortisol was lower in
caesarean born subjects as compared to normal born neonates. On the other hand
uric acid concentration was higher in caesarean born neonates. CONCLUSION: The
obtained data indicated that babies born via caesarean section might be
predisposed to pathological conditions due to altered antioxidant levels.
PMID- 27504276
TI - A Study of the Extended Lipid Profile including Oxidized LDL, Small Dense LDL,
Lipoprotein (a) and Apolipoproteins in the Assessment of Cardiovascular Risk in
Hypothyroid Patients.
AB - INTRODUCTION: Hypothyroidism is one of the most common metabolic disorders
associated with dyslipidemia which poses a higher risk of Coronary Artery Disease
(CAD) in such patients. Biochemical markers which can pick up the risk promptly
are becoming imperative now-a-days and thus the assessment beyond the
conventional lipid profile is the need of the hour. AIMS: To assess the
association of non-conventional lipid parameters like small dense Low Density
Lipoprotein (sd LDL), oxidized Low Density Lipoprotein (ox LDL), Apolipoprotein A
(Apo A1), Apolipoprotein B (Apo B) and Lipoprotein (a) {Lp(a)} in hypothyroid
patients and compare their values with the conventional lipid parameters such as
Total Cholesterol (TC), Triglyceride (TG), Low-Density Lipoprotein Cholesterol
(LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C). MATERIALS AND METHODS:
One hundred and thirty clinically proven patients of hypothyroidism aged 20-60
years and equal number of age and gender matched healthy individuals were
included in this case control study. Serum sd LDL, ox LDL, Apo A1, Apo B, Lp (a),
lipid profile, Thyroid Stimulating Hormone (TSH), Free Triiodothyronine (FT3) and
Free Tetraiodothyronine (FT4) levels were measured in both the groups. The data
was recorded and analysed on SPSS system. The results of cases and controls were
compared by student t-test and one-way ANOVA. All the parameters were correlated
with TSH by Pearson's correlation. RESULTS: We found significantly high levels of
sd LDL, ox LDL, Apo B, Lp (a), TC, TG, LDL-C in cases as compared to the
controls. Ox LDL has shown maximum correlation with serum TSH (p<0.0001, r=0.801)
followed by sd LDL (p<0.0001, r=0.792), Apo B (p<0.001, r=0.783) and LDL-C
(p<0.001, r=0.741). Moreover, ox LDL and sd LDL were found to be increased in
normolipidemic hypothyroid patients thereby giving a strong supportive evidence
that estimation of these parameters can become fundamental in prompt
identification of the high risk patients of CAD in hypothyroid population.
CONCLUSION: Non-conventional lipid parameters appear to be better markers for the
assessment of cardiovascular risk in hypothyroidism and might help in the
designing of the effective treatment protocols and areas of intervention by the
clinicians as well as researchers.
PMID- 27504277
TI - Aptamers in Therapeutics.
AB - Aptamers are single strand DNA or RNA molecules, selected by an iterative process
known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due
to various advantages of aptamers such as high temperature stability, animal
free, cost effective production and its high affinity and selectivity for its
target make them attractive alternatives to monoclonal antibody for use in
diagnostic and therapeutic purposes. Aptamer has been generated against vesicular
endothelial growth factor 165 involved in age related macular degeneracy. Macugen
was the first FDA approved aptamer based drug that was commercialized. Later
other aptamers were also developed against blood clotting proteins, cancer
proteins, antibody E, agents involved in diabetes nephropathy, autoantibodies
involved in autoimmune disorders, etc. Aptamers have also been developed against
viruses and could work with other antiviral agents in treating infections.
PMID- 27504278
TI - The Long Term Kinetic of Plasma Lipids and Lipoproteins in Tyloxapol Injected
Rats.
AB - INTRODUCTION: The level of plasma triglyceride is balanced by the rate of
secretion into and clearance from the plasma. Tyloxapol (Triton WR1339) is a
nonionic detergent that inhibits lipoprotein lipase and hence clearance of
triglyceride from the plasma. AIM: To determine the kinetic of plasma lipids and
lipoproteins following injection of tyloxapol over a period of two weeks.
MATERIALS AND METHODS: Fifteen male rats were starved over-night and injected
intravenously with tyloxapol (400mg/kg). Blood samples were taken in three steps
as, the early (1-6 hours), the middle (1-2 days) and the third (3-9 days) phase.
Plasma total cholesterol and triglyceride were measured by enzymatic methods and
total phospholipids were analysed as molybdenum blue. Serum lipoproteins were
fractionated by electrophoresis on agarose gel (Sebia Inc). RESULTS: The changes
of plasma lipids following tyloxapol injection showed three distinctive phases.
The early phase lasts at least 6 hours, and the concentrations of triglyceride,
total cholesterol and phospholipids increased linearly. The rate of triglyceride
secretion was 259.7 +/- 8.1 mg/h.dl in this phase, which was comparable to the
mean rate of 250.6 +/- 37.0 mg/h.dl or 102.8 +/- 15.2 mg/h.kg body in starved
male rat. During the next 48 hour the lipids continued to accumulate but at a
lower rate, and the levels of triglyceride, cholesterol and total phospholipids
rose up to about 3200, 586 and 715 mg/dl respectively. In the last phase, the
levels of plasma lipids decreased toward the basal levels after 5 days. In serum
lipoprotein electrophoresis, the VLDL and LDL increased and HDL fraction
disappeared simultaneously during the initial 2 hours of tyloxapol injection. The
VLDL fell down toward the normal range, preceded to the reappearance of HDL
during 5 days. CONCLUSION: A single intravenous injection of tyloxapol shows
three distinctive phases. In the early phase, triglyceride accumulates linearly
and the rate of its increment in plasma is a good estimate of the rate of VLDL
secretion from the liver.
PMID- 27504279
TI - Effects of Diaceto-Dipropyl-Disulphide on Plasma Sialic Acid and Renal Tissue
Thiol Levels in Alloxan Diabetic Rats.
AB - INTRODUCTION: Plasma sialic acid levels are elevated in Diabetes Mellitus (DM)
patients with proteinuria. Renal damage is mainly caused by free radicals that
are excessively generated in DM. Thiols play an important role in the cellular
antioxidative defence mechanisms mainly through thiol-disulphide exchange
reaction. Diallyl disulphide, a garlic oil principle component, is known for its
anti-diabetic properties. Its structural analogue, Diaceto-Dipropyl Disulphide
(DADPDS), is a less toxic and more palatable disulphide and possesses similar
anti-diabetic actions. AIM: This study was undertaken to assess the usefulness of
DADPDS in prevention of de-sialation of Glomerular Basement Membrane (GBM) in
alloxan diabetic rats and to assess effect of DADPDS on renal tissue thiol
levels. MATERIALS AND METHODS: Rats were divided into Normal, Diabetic and DADPDS
treated diabetic groups. Diabetes was induced by intraperitoneal injection (IP)
of alloxan. DADPDS was fed by gastric intubation. Plasma Sialic acid was
determined by Ehrlich's method and renal tissue thiol levels by Nitroprusside
reaction method. RESULTS: This study showed a significant decrease (p<0.001) in
plasma sialic acid, plasma glucose and renal tissue TBARS levels along with
significant increase (p<0.001) in renal tissue thiol levels in DADPDS treated
alloxan diabetic rats when compared to diabetic control rats. CONCLUSION: Hence
it may be concluded that DADPDS helps in preventing de-sialation of GBM in
alloxan diabetic rats and improves renal tissue antioxidant defence mechanisms,
may be through thiol-disulphide exchange reaction and thereby exhibits a possible
clinical use in prevention of renal complications like diabetic nephropathy.
PMID- 27504280
TI - Anthropometric Predictors of Bio-Impedance Analysis (BIA) Phase Angle in Healthy
Adults.
AB - INTRODUCTION: Phase Angle (PhA) is a ratio of whole body reactance and resistance
obtained from Bioelectrical Impedance Analysis (BIA). It indicates cellular
health and integrity and is considered as prognostic tool in medical disorders.
In spite of prognostic potentials of PhA, it has limited usefulness in clinical
practice and in population studies because of non-availability of normal
population reference limits for comparison. Moreover, it is influenced by various
factors like age, sex, race and body composition (i.e. body fat, muscle mass,
visceral fat, body cell mass, total body water, etc). AIM: The aim of this study
was to evaluate predictors of phase angle which will be useful in formulation of
reference values for Indian population. MATERIALS AND METHODS: BIA was performed
by Tanita Body Composition Analyser on healthy adults aged 17-24 years. The
inbuilt software measured the phase angle by the formula: Phase angle (PhA) =
Reactance (xc)/Resistance (R)* (180/pi). Phase angle values were compared across
categories of age, sex, weight, height, Body Mass Index (BMI), total fat,
visceral fat and muscle mass. RESULTS: Mean value of phase angle was found to be
5.65. Phase angle was significantly (p< 0.001) higher in male than in female.
Phase angle was significantly predicted from height (p< 0.001), weight (p<
0.002), muscle mass (p< 0.002) and visceral fat (p< 0.02) in multiple regression
models. CONCLUSION: Phase angle differs across anthropometric and body
composition categories. Thus height, weight and muscle mass should also be taken
into consideration while deriving population specific reference limits of phase
angle.
PMID- 27504281
TI - Serum Proteins Alteration in Association with Body Mass Index in Human
Volunteers.
AB - INTRODUCTION: Serum proteins are an important indicator of the nutritional status
in an individual. There is a worldwide prevalence of both undernourishment and
obesity. It has been suggested that low Body Mass Index (BMI) is associated with
a decrease in serum protein levels predisposing them to other illnesses.
Overweight and obese individuals carry risk for various other non-communicable
diseases. AIM: To compare the serum protein levels in underweight, overweight and
obese individuals with that of normal body mass index individuals. MATERIALS AND
METHODS: This prospective study was conducted in subjects who attended the master
health checkup clinic of PSG hospitals. Subjects in the age group of 20-50 years
were selected. Their serum proteins and BMI was measured. Twenty subjects each of
underweight, normal, overweight and obese individuals were selected, categorized
and compared. RESULTS: The serum protein level of normal individuals (Group I)
was compared with underweight (Group II), overweight (Group III) and obese
subjects (Group IV) by one-way ANOVA analysis. The mean serum total proteins in
gm/dl in group I controls was 7.555+/-0.37 compared to Group II (underweight)
which was 7.295+/-0.419. Low BMI was found to be associated with a decrease in
serum protein level which was not statistically significant. Elevated BMI as in
overweight and obese subjects showed no significant alterations in serum protein
levels with p >0.05 and the changes were found to be independent of the body mass
index. CONCLUSION: Underweight individuals showed a decrease in serum protein
levels whereas there were no significant changes in the serum protein levels in
overweight and obese individuals.
PMID- 27504282
TI - A Study on the Impact of Hyperhidrosis on the Quality of Life among College
Students.
AB - INTRODUCTION: Hyperhidrosis (HH) is a condition characterized by excessive
sweating or perspiration. General population, especially in developing countries
like India are seldom aware of this condition and sparsely seek medical
attention. The tropical climate and the environment also influence this condition
to a greater extent. This can be a hindrance in their professional and social
life. Though, it is a widely explored topic, studies on hyperhidrosis from India
are rare. AIM: The current study was aimed at estimating the prevalence of
hyperhidrosis among college students subjectively and to assess the quality of
life using Dermatology Life Quality Index (DLQI). MATERIALS AND METHODS: Five
hundred students with age ranging from 17 to 21 years of both genders were
included in this study using convenient sampling method. After explaining the
study and getting written consent, the students were requested to respond to two
questionnaires, one for the subjective diagnosis of hyperhidrosis using a
standardized questionnaire developed by North Jersey Thoracic Surgical Associates
and the other to assess the quality of life using DLQI. Based on the subjective
prevalence scores, the students were divided into 3 groups as "Not bothersome"
group, "Somewhat bothersome group" and "Extremely bothersome" group. The DLQI
scores of these three groups were compared by ANOVA using SPSS 21.0. RESULTS: The
study revealed that overall, 38% of the students were suffering from somewhat
bothersome to extremely bothersome hyperhidrosis. Gender analysis showed that
male students were affected more (58%), especially with palmar hyperhidrosis and
were significantly requiring treatment when compared to female students. Analysis
of DLQI scores using ANOVA revealed the fact that overall quality of life was
significantly affected in almost 35% of students to the extent that they require
appropriate treatment and care. CONCLUSION: This study brings into light the
higher prevalence of hyperhidrosis and also its impact on the quality of life
among college students in this tropical region.
PMID- 27504283
TI - Dengue: Lessons of an Outbreak.
AB - INTRODUCTION: Since 1967 there have been many outbreaks of dengue in Delhi. In
the year 2015 Delhi has suffered it's one of the worst dengue outbreaks, with
more than 15000 dengue confirmed cases and the highest number of deaths (60) in
recent years. AIM: To determine the status of Dengue cases as compared to
previous six years, the ratio of primary and secondary dengue cases and to review
the effectiveness of the one test strategy (either NS1 antigen or IgM antibody)
for the confirmation of Dengue. MATERIALS AND METHODS: A cross-sectional study
was performed in the year 2015. A total of 7177 serum samples were tested for the
confirmation of suspected cases of dengue at our institute. We performed dengue
NS1 antigen and dengue IgM antibody ELISA tests for the confirmation of dengue
cases in acute and convalescent fever cases respectively. Hundred random samples
negative for NS1 antigen were tested for IgM antibody and 100 random samples
negative for IgM antibody were tested for NS1 antigen. For determination of ratio
of primary and secondary dengue cases, IgG Avidity ELISA was performed on random
76 dengue positive samples. RESULTS: Out of 7177 samples tested, 2358 were
positive either by NS1 antigen or for IgM antibody from January to December.
Percentage positivity rates for IgM antibody detection and NS1 antigen detection
tests were 24.8% (626) and 37.1% (1732) respectively. Out of 100 NS1 negative
samples 8 were positive for IgM antibody and out of 100 IgM negative samples 6
were positive for NS1 antigen. Among the 76 samples tested for dengue IgG Avidity
ELISA 52 (68.4%) were found to be of secondary dengue. CONCLUSION: Number of
dengue cases is constantly rising in Delhi since 2011 and 2014. IgM antibody
detection and NS1 antigen detection both the tests should be performed for each
patient. Due to the increased prevalence of past infection of dengue, percentage
of secondary dengue cases is also increasing in Delhi.
PMID- 27504284
TI - Molecular Characterisation of nfsA Gene in Nitrofurantoin Resistant Uropathogens.
AB - INTRODUCTION: Majority of Urinary Tract Infections (UTI's) are lower UTI's which
constitute the real burden in the primary care setting and are usually treated
empirically. Nitrofurantoin is an underused antimicrobial for empiric therapy for
community-acquired and nosocomial lower UTIs. Nitrofurantoin has a wide spectrum
of action against Escherichia coli, Klebsiella pneumonia and Enterococci, which
are the frequent causes of nosocomial lower UTIs and also against multidrug
resistant gram-negative organisms including extended spectrum beta lactamase
(ESBL) producers, Amp-C producers and Carbapenamase producers. AIM: The study was
conducted to describe the resistance pattern of nitrofurantoin and to identify
the genes responsible for nitrofurantoin resistance (i.e.) nfsA and the type of
mutations involved. SETTINGS AND DESIGN: This study was conducted in a tertiary
care hospital for a period of six months which caters to a total of 1200 beds.
MATERIALS AND METHODS: A total of 115 clinical strains of Escherichia coli and
Klebsiella pneumoniae including ESBL and Carbapenemase producing isolates were
analysed for susceptibility to commonly used antimicrobials. RESULTS: ESBL
producers 65% and 51% of carbapenems resistant strains were susceptible to
nitrofurantoin by minimal inhibitory concentration. MIC to nitrofurantoin was
determined by E-strip method. Nitroreductase nfsA gene was detected by PCR in 64
of 70 E.coli isolates with reduced susceptibility to nitrofurantoin. Gene
sequencing was done using BLAST algorithm and substitution (N=12) and insertion
mutation (N=1) were observed in the resistant strains. CONCLUSION: Nitrofurantoin
being an oral antibiotic, its usage in ESBL producers and carbapenamase producers
is still warranted. Surprisingly, resistance to nitrofurantoin remains minimal
even after extensive use and may be related to the fact that it has multiple
mechanisms of action hence may require organisms to develop more than a single
mutation to concur resistance.
PMID- 27504285
TI - Detection of Respiratory Syncytial Virus using Direct Fluorescent Antibody Assay
in Paediatric Patients with Acute Respiratory Tract Infection.
AB - INTRODUCTION: Severe Respiratory Syncytial Virus (RSV) pulmonary disease
manifesting as bronchiolitis and pneumonia continues to play a major role in the
childhood mortality and morbidity. Hence the present study was undertaken to
evaluate the prevalence of RSV among hospitalized children presenting with Acute
Respiratory Tract Infection (ARTI) and its correlation with risk factors. AIM: To
determine the occurrence of RSV related respiratory tract infection in paediatric
patients and to access the risk factors and clinical features associated.
MATERIALS AND METHODS: RSV antigen detection was performed by Direct Fluorescent
Antibody (DFA) staining on 100 nasopharyngeal aspirate collected from
hospitalized children below 5 years of age with a diagnosis of ARTI. RESULTS: Out
of the 100 samples tested for RSV with DFA, 22 (22%) were found RSV positive with
a mean age of 12 months and a male to female ratio of (1.75:1). Clinical features
significantly associated with RSV were wheezing and breathlessness. Congenital
heart disease (CHD) and prematurity were the risk factors significantly
associated with RSV infection. CONCLUSION: RSV infection is a significant cause
of morbidity among children presenting with ARTI. In resource limited countries
DFA can be used as an important tool for rapid detection of RSV and can
potentially eliminate prolonged hospitalization and unnecessary use of
antibiotics.
PMID- 27504286
TI - Pyogenic Liver Abscess Caused by Acinetobacter lwoffii: A Case Report.
AB - Acinetobacter lwoffii is a gram negative aerobic non-fermenter bacilli. It is
considered as an important emerging pathogen after Acinetobacter baumannii in
patients with impaired immune system and in nosocomial infections. Here, we
present a case of community acquired pyogenic liver Abscess caused by
Acinetobacter lwoffii in a diabetic patient.
PMID- 27504287
TI - Acute Pancreatitis, Hepatitis and Bone Erosion in Acute Yellow Phosphorous
Compound Poisoning - A Rare Complication.
AB - We report a case of acute pancreatitis and hepatitis following ingestion of
yellow phosphorous. The condition of the patient progressed to encephalopathy and
bony erosion of the nasal septum. Fungal mass was observed in both the nasal
cavities by endoscopy. Microbiological investigation revealed the identity of the
fungus as Aspergillus flavus and Candida tropicalis. Patient improved with
fluconazole treatment.
PMID- 27504288
TI - Biofilm in Osteomyelitis caused by a Rare Pathogen, Morganella morganii : A Case
Report.
AB - Morganella morganii is a member of Enterobacteriaceae family, whose natural
habitat is the human gastrointestinal tract. It rarely causes infection alone and
is generally encountered in immunosuppressed patients. Osteoarticular pathologies
are not commonly observed with Morganella morganii and infections by it have high
mortality rate. Biofilm colonization is a causative factor behind the chronicity
and/or refractoriness of certain infections. Biofilms colonize on inert medical
devices, prosthesis, fibrosed tissues, sinus tracts as well as dead bones as in
case of chronic osteomyelitis. Morganella morganii is not a common pathogen to
produce biofilm. In this case report, we present a 56-year-old male patient with
chronic osteomyelitis of right proximal tibia caused by biofilm producing strain
of Morganella morganii, following trauma.
PMID- 27504289
TI - Detection of Salivary IgA Antibodies Against the HlyE Antigen as a Diagnosis of
Typhoid Fever.
AB - INTRODUCTION: The Salmonella typhi (S. typhi) haemolysin E protein (HlyE) has
been shown to be a sensitive and specific antigen for the detection of typhoid
fever through the detection of anti-HlyE antibodies in sera. Saliva can also be a
useful diagnostic fluid as it also contains antibodies against bacterial
pathogens. AIM: This study aims to evaluate the potential detection of salivary
anti-HlyE antibodies as a diagnosis of typhoid fever. MATERIALS AND METHODS:
Saliva was collected from acute typhoid patients (n=16) who presented at Hospital
Universiti Sains Malaysia with prolonged fever of more than five days and were
positive for S. Typhi blood culture. Saliva was also collected from convalescent
typhoid patients (n=11), patients with other febrile fevers (n=15), and from
healthy individuals (n=25). An ELISA was developed to detect the presence of IgA
antibodies against HlyE in the saliva of typhoid patients. RESULTS: The acute
typhoid group had a higher mean absorbance value of 1.496 compared to the
convalescent typhoid (0.538), other febrile fevers (0.678), and healthy
individuals (0.457) group. CONCLUSION: This study demonstrated the utility of
salivary anti-HlyE IgA antibody as a biomarker for the diagnosis of typhoid
fever. Follow-up studies with a larger sample size will allow the optimization of
the sensitivity and specificity of the assay. This non-invasive method can be
useful for mass screening programs.
PMID- 27504290
TI - Expression of Cytokeratin-19 and Thyroperoxidase in Relation to Morphological
Features in Non-Neoplastic and Neoplastic Lesions of Thyroid.
AB - INTRODUCTION: Thyroperoxidase (TPO) is a protein involved in thyroid hormone
synthesis. TPO gene suppression and mutation were involved in thyroid tumours. CK
19 plays important role in the structural integrity of epithelial cells. Reduced
TPO expression with increased CK-19 immunoreactivity has been implicated as a
marker for differentiating non neoplastic and neoplastic thyroid lesions. AIM: To
study the histopathological features of thyroid lesions and to evaluate the
diagnostic role of thyroperoxidase and CK-19 in non-neoplastic and neoplastic
thyroid lesions. MATERIALS AND METHODS: Prospective observational study of 65
thyroid specimens was studied for detailed histopathological examination and
Expression of Immunohistochemical Markers Cytokeratin-19 (CK-19) and
Thyroperoxidase. RESULTS: TPO IHC marker was expressed by non-neoplastic and
benign lesions of thyroid but not in malignancy. CK-19 was expressed 100% in
papillary carcinoma of thyroid and its variants, focal and weak staining noted in
goitre and hyperplastic areas. CONCLUSION: Most of the non-neoplastic and
neoplastic lesions were diagnosed based on histopathological features. When the
histopathological diagnosis are equivocal, immunohistochemical markers aids in
diagnosing malignancy. Diffuse and strong TPO expression indicates non-neoplastic
thyroid lesions whereas diffused and strong CK-19 expression indicates thyroid
malignancy.
PMID- 27504291
TI - Morphological Spectrum of Basal Cell Carcinoma in Southern Karnataka.
AB - INTRODUCTION: Basal Cell Carcinoma (BCC) is the most common skin cancer
worldwide, which appears over sun-exposed skin as slow-growing, locally invasive
lesion that rarely metastasizes. Many phenotypic presentations are possible. BCCs
are more common in males and tend to occur in older people. Majority is found on
the head and neck. Many histopathological subtypes have been defined including
nodular, micronodular, cystic, superficial, pigmented, adenoid, infiltrating,
sclerosing, keratotic, infundibulocystic, metatypical, basosquamous and
fibroepitheliomatous. Mixed patterns are common. AIM: The aim was to study
morphological spectrum of BCC in a tertiary care hospital in southern Karnataka.
MATERIALS AND METHODS: This was a retrospective analysis of 100 cases of BCCs
reported in the Department of Pathology over a 9-year period from 2006 to 2014.
RESULTS: The mean age of presentation was 62 years. There was slight female
preponderance (56%). The most common location was face (65%) and the most common
presentation was ulceration (45%). Of the 100 BCCs, 50% were nodular, 13%
infiltrating, 6% basosquamous, 4% superficial, 3% keratotic, 3% multinodular and
1% mixed. CONCLUSION: BCC, besides being the commonest cutaneous cancer, is also
known for its numerous histological patterns which are shown to have prognostic
implications. This study reveals the frequency of the various histological
patterns of BCC in southern Karnataka, where it has been rarely studied before.
PMID- 27504292
TI - Anaemia in Systemic Lupus Erythematosus Based on Iron Studies and Soluble
Transferrin Receptor Levels.
AB - INTRODUCTION: Haematological alterations such as anaemia, neutropenia and
thrombocytopenia are frequent in Systemic Lupus Erythematosus (SLE). Ferritin
being an acute phase reactant can be falsely elevated in lupus cases. AIM: To
evaluate the haematological alterations and to re-categorise the types of anemia
by soluble transferrin receptor levels in diagnosed cases of SLE. MATERIALS AND
METHODS: A sample of 30 newly diagnosed ANA positive SLE patients was taken.
Complete blood counts, ESR, reticulocyte count, coagulation studies, diluted
Russel Viper Venom Test (dRVVT), mixing studies, serological tests, high
sensitivity CRP along with iron profile, transferrin saturation, soluble
transferrin receptor (sol TFR) levels, anti-beta2 glycoprotein1, direct and
indirect Coomb's test were estimated in cases diagnosed as SLE. Clinical symptoms
were co-related with and Systemic Lupus Erythaematosus Disease Activity Index
(SLEDAI) was estimated. RESULTS: Anaemia was the most prevalent haematological
alteration followed by thrombocytopenia. Further sub typing of anaemia was done
by serum ferritin levels and using sol TFR assays. Ferritin is an acute phase
reactant; it underestimated iron deficiency in patients of SLE. When sol TFR was
used; patients with pure Anaemia of Chronic Disease (ACD) reduced from 68% to
26%, those with pure IDA reduced from 32% to 16% and a group with co-existing IDA
& ACD (58%) was defined {Agreement=53%, p=0.09} by sol TFR which co-related with
clinical response to Iron therapy in these patients. CRP was significantly raised
in association with disease activity. Fever (p<0.0001), arthritis (p<0.03) were
significantly related and CRP was elevated (p<0.04) in cases with high SLEDAI
(severe flare). CONCLUSION: Thus, in SLE, anaemia is the most frequent
hematological alteration; iron deficiencies supercede in contrast to ACD and
further autoimmune haemolytic anaemia. Sol TFR emerged as a better parameter to
detect iron deficiency in patients of non- haemolytic anaemia in contrast to iron
profile and ferritin levels.
PMID- 27504293
TI - Enigmatic Weak D antigen: An Experience in a Tertiary Care Hospital of East
Delhi.
AB - INTRODUCTION: The Rh blood group system is one of the most polymorphic and
immunogenic blood group systems in humans. The expression of Rh blood group
antigen is complex, among that Rh-D antigen is the most important antigen because
of its immunogenicity. It is easy to detect D antigen in most of the cases.
Sometimes, variable expression of Rh-D antigen leads to presence of weak forms.
Weak D reacts variably with anti D sera and poses a problem in blood banking.
Molecular genetics of Rh-D revealed that weak D antigen is a Rh-D phenotype that
possesses less numbers of complete D antigens on the surface of red blood cells.
AIM: Present study was carried out to study weak D positivity in a tertiary
neuropsychiatry hospital of East Delhi for compatibility testing in blood
transfusion, to assess the implications and need of weak D testing and for
population genetics study. This study tried to observe pattern of weak D antigen
in four broadly classified religious communities also (Hindus, Muslims, Sikhs and
Christians). MATERIALS AND METHODS: This was a two years prospective hospital
based study including patients as well as donors. All patients were tested for Rh
D factor by commercially available monoclonal anti-D sera. The individuals who
were found negative with anti-D were further investigated for weak D antigen by
using indirect antiglobulin test (IAT) by tube as well as gel card technique.
RESULTS: The results were compiled by using SPSS software version 21.0 and
Microsoft excel. Among 3619 cases, 3502 (96.7%) were Rh-D factor positive while
117(3.2%) were Rh D factor negative. Among these 117 Rh-D negative cases, 9 (7.6%
out of total Rh-D negatives and 0.25% out of total samples) were weak D positive
and 108(2.98%) were actually D negative individuals after IAT. Weak D positivity
showed a slight predominance in females (55.5%). As per broad religious
communities, weak D antigen was found in Hindus only and not observed in Muslims,
Sikhs and Christians. In weak D positive individuals, B phenotype (0.43%) was
found to be most common followed by A (0.26%) and O (0.2%). CONCLUSION:
Considerably high frequency of weak D antigen was noticed in study samples of
this hospital. With this data based information, it is felt worthwhile to perform
weak D testing routinely of those individuals who are negative with saline anti-D
to prevent possibility of haemolysis and for efficient blood transfusion
practices by making compatible blood available.
PMID- 27504294
TI - Histopathological Trends of Testicular Neoplasm: An Experience over a Decade in a
Tertiary Care Centre in the Malwa Belt of Central India.
AB - INTRODUCTION: Testicular and para-testicular neoplasm are rare type of tumours
affecting adolescents and young adults, reflected by the paucity of published
data in India. AIM: This study was undertaken to estimate the epidemiological
characteristics and histological types and subtypes of testicular neoplasm
according to the WHO classification in our patient group. Identification of
histopathological pattern of testicular tumour is immensely important for
improved management protocols. MATERIALS AND METHODS: This was a retrospective
study done over a period of ten years from 2004 to 2014 in a tertiary care
centre. All relevant clinical data including patient's age, laterality, history
of risk factors and serum tumour markers were collected from records.
Histopathological slides were retrieved and reviewed for tumour and its subtype
and classified according to WHO classification (2004). RESULTS: A total of 37
cases of testicular and paratesticular neoplasm were encountered in our study
with a mean age of 38.1 years. Right testis was affected in 70.3% of cases. The
most common clinical presentation was scrotal swelling with heaviness. Germ cell
tumour was the most common type accounting for 77.1% followed by lymphomas
(17.1%). Germ cell tumours were categorized into seminomatous (48.2%) and non
seminomatous tumours (51.8%). The most common subtype of non-seminomatous tumours
was mixed germ cell tumour accounting for 85.8%. CONCLUSION: The incidence of
testicular neoplasm among general population in Asian countries is low, as
reflected in the very few studies that have been performed and published in
literature. Epidemiological and histomorphological spectrum of our study was
comparable to most of the countries except for some African and Western
countries.
PMID- 27504295
TI - Clinicopathological Study of Non-Infectious Erythaematous Papulosquamous Skin
Diseases.
AB - INTRODUCTION: Papulosquamous diseases are characterized by scaly papules and
plaques with similar clinical picture which amounts to confusion and hence, a
definitive histopathological diagnosis goes a long way in treatment of such
diseases. AIM: The aim of the study was to study the histomorphology of non
infectious, erythaematous, papulosquamous lesions of skin with
clinicopathological correlation. MATERIALS AND METHODS: Skin biopsies from 150
clinically diagnosed/suspected non-infectious erythaematous, papulosquamous skin
diseases were received in the Department of Pathology. The specimens obtained
were subjected to formalin fixation and paraffin embedding, stained with
haematoxylin and eosin and studied. The lesions were classified as psoriasis,
lichen planus, lichen nitidus, lichen striatus, pityriasis rosea and pityriasis
rubra pilaris and clinicopathological correlation was done. RESULTS:
Papulosquamous lesions were common in the elderly. Males were commonly affected
except in pityriasis rosea. Among the 150 cases studied, 72 cases (48%) were
histopathologically confirmed to be papulosquamous lesions. Psoriasis was the
most common lesion. CONCLUSION: Key histopathological features and
clinicopathological correlation gives a conclusive diagnosis. The importance of
specific histomorphological diagnosis lies in distinguishing these lesions as the
treatment and prognosis varies widely.
PMID- 27504297
TI - Papillary Cystadenocarcinoma of the Parotid Gland: A Rare Case Report.
AB - Papillary cystadenocarcinoma is a rare malignant neoplasm of the salivary gland,
characterized by noticeable cystic and solid areas with papillary endophytic
projections. These tumours lack features that characterize cystic variants of
several more common salivary gland carcinomas. It was first described in 1991 by
World Health Organization as a separate entity and cystadenocarcinoma with or
without papillary component in the AFIP classification. Most of these tumours
occurred in the major salivary glands followed by minor salivary glands.
Cystadenocarcinoma is the malignant counterpart of cystadenoma. We report a case
of papillary cystadenocarcinoma of parotid. A 40-year-old lady presented with
gradually progressive swelling below the right ear associated with occasional
pain. Clinical and radiological features suggested benign neoplasm. Right lobe
superficial parotidectomy was performed. The histopathologic diagnosis showed
papillary cystadenocarinoma of the parotid gland. Histologic confirmation of
stromal invasion is required to differentiate it from the benign lesion.
Conservative wide local surgical excision is the treatment of choice.
PMID- 27504296
TI - Diagnostic and Prognostic Significance of Various Histopathological Features in
Extrahepatic Biliary Atresia.
AB - INTRODUCTION: Extrahepatic biliary atresia is a progressive disorder
characterised by fibroinflammatory obliteration or stenosis of the extrahepatic
biliary tree leading to obstruction of bile flow and cholestatic jaundice. It is
the most common cause for cholestasis in newborn. Histopathological criteria for
diagnosing biliary atresia from liver biopsy have not been clearly defined. AIM:
This study was undertaken to analyse the significance of the various
histopathological features in diagnosis and prognosis of extrahepatic biliary
atresia from liver biopsy specimens. MATERIALS AND METHODS: This was a
retrospective study of 43 cases of extra-hepatic biliary atresia diagnosed and
treated at a tertiary care hospital between January 2010 to December 2014.
Formalin fixed paraffin embedded liver biopsy tissues were processed by standard
technique and the slides were stained with haematoxylin and eosin. All the slides
were reviewed and graded by a semi-quantitative scoring system. Features such as
increased age at kasai's portoenterostomy, portal fibrosis, bile duct
proliferation, cholestasis, portal inflammation and duct plate malformation were
studied. Statistical analysis was worked out using SPSS 17.0 (statistical package
for the social science software). Chi-square test was used to find association
between various parameters with respect to mortality and Kaplan-Meier estimator
was used for survival analysis of the population under study. RESULTS: In this
study comprising of 43 cases, only 6 cases (13.95%) were alive at the end of 6
months follow-up. Twenty patients who died and the 17 cases with poor survival
had greater degrees of fibrosis, bile duct proliferation and cholestasis.
Majority of the cases with duct plate malformation expired inspite of earlier
surgical intervention. Thus proving the association of fibrosis, bile duct
proliferation, cholestasis and duct plate malformation with the survival and
prognosis of biliary atresia cases. Age at surgery did not show any correlation
with prognosis as cases operated even at <60 days had poor survival. CONCLUSION:
From this study it can be concluded that in extrahepatic biliary atresia
patients, presence of duct plate malformation, greater degrees of fibrosis, bile
duct proliferation and cholestasis were strongly associated with poor prognosis.
PMID- 27504298
TI - Non-Secretory Myeloma, Diagnosed on Renal Biopsy as Cast Nephropathy.
AB - Multiple myeloma is a disorder of plasma cells which can involve kidneys in the
form of cast nephropathy. Neoplastic plasma cells produce either complete
immunoglobulins or fragments of immunoglobulins leading to a monoclonal spike in
the serum and/or Bence Jones proteinuria. Very few patients present as non
secretory myeloma when no immunoglobulins (M spike) are produced or only light
chains are secreted which can only be detected in urine. Acute renal failure due
to cast nephropathy can rarely be the first presentation of multiple myeloma. We
here in report a case in which primary diagnosis of multiple myeloma was made on
renal biopsy due to its characteristic histomorphology. The diagnosis was later
on supported by presence of neoplastic plasma cells in the aspirate and biopsy of
bone marrow.
PMID- 27504299
TI - A Solid Pseudopapillary Tumour of the Head of Pancreas: A Rare Case Report
Diagnosed by Fine Needle Aspiration Cytology.
AB - Solid Pseudopapillary Tumour (SPPT) is a distinctive tumour of low malignant
potential with a striking and unexplained predilection for adolescent girls and
young women. Hence it is important to distinguish this rare tumour from other
pancreatic tumours with similar cytomorphologic features because an accurate
preoperative diagnosis is highly desirable since these patients can have long
survival with adequate surgery. We report a case of the rare SPPT of the pancreas
in a young girl who presented with nonspecific pain in the abdomen. Radiological
investigations revealed a solid cystic mass in relation to the uncinate process
of pancreas and third part of duodenum. The mass was diagnosed to be a solid
pseudopapillary neoplasm of pancreas on ultrasound guided FNAC. Surgical removal
of the pancreatic tumour and detailed histologic study confirmed the cytologic
diagnosis. We present this case because, to date, there are few case reports on
the cytological diagnosis of this tumour, about 60 cases, diagnosed by Fine
Needle Aspiration Cytology (FNAC) are reported in the literature. With widespread
availability of high-quality imaging systems and a better understanding of its
pathology, the number of cases reported in the literature has been steadily
increasing in recent years. In our case, the cytological diagnosis was done even
before the detailed imaging findings were available, the cytological features of
this tumour are highly characteristic and it is possible to differentiate it from
other pancreatic tumours with relative ease.
PMID- 27504300
TI - Idiopathic Fatal Pancytopenia: A Case Report.
AB - Pancytopenia is defined as decrease in red blood cells, white blood cells and
platelets. Many disease processes involve the bone marrow primarily or
secondarily resulting in pancytopenia. A 55-year-old male presented with
generalized body weakness and few episodes of malena for last one year. Physical
and systemic examination was unremarkable. CBC report revealed pancytopenia.
Other haematological parameters were within normal limit. Stool for occult blood
was positive. USG and CECT abdomen showed no abnormality. The patient was
evaluated for any evidence of malignancy but no clue was found. Bone marrow
examination was done as patient was having pancytopenia. Bone marrow smears, clot
sections and bone marrow biopsy was normal. Immunohistochemistry and cytogenetics
study was unremarkable. Patient was admitted in hospital for 1 month and his
condition rapidly deteriorated. The cause of pancytopenia remained unexplained
and therefore it was named as Idiopathic fatal pancytopenia. "Idiopathic Fatal
Pancytopenia (IFP)" is an emerging new entity with a grave prognosis. We wish to
sensitize the medical community and the scientists to this rapidly fatal
condition.
PMID- 27504301
TI - Tufted Angioma of Eyelid in an Adult - A Case Report.
AB - Tufted Angiomas also known as angioblastomas /Angioblastoma of Nagakawa are rare
vascular neoplasms localised to the skin and subcutaneous tissues with the upper
trunk and neck being most common sites. They are mainly seen in children but a
few cases in juveniles and adults have been reported. We hereby report this case,
a 40-year-old male who presented with a right lower lid, painless, slowly
progressive, firm swelling diagnosed as Tufted Angioma on histopathology and
immunohistochemistry.
PMID- 27504302
TI - Aneurysmal Bone Cyst: An Uncommon Secondary Event in Calcaneal Chondroblastoma.
AB - Chondroblastoma is an uncommon benign bone tumour, involvement of epiphysis of
long bones is typical. Chondroblastoma of the calcaneum is uncommon and its
association with secondary aneurysmal bone cyst is even rarer. Only two cases of
calcaneal chondroblastoma associated with secondary aneurysmal bone cyst have
been reported till date. A 22-year-old male presented to the department of
orthopaedics with complains of pain and swelling in the left heel since the last
10 months. On clinico-radiological grounds differentials considered were giant
cell tumour of bone and aneurysmal bone cyst. In view of the histopathological
findings of bone curettage and results of special stain and immunohistochemical
marker, final diagnosis of chondroblastoma with secondary aneurysmal bone cyst,
left calcaneum was rendered. Although rare, chondroblastoma should always be
considered in osteolytic lesions of calcaneum. The identification of secondary
aneurysmal bone cyst component is important as it has higher chances of
recurrence than usual chondroblastoma.
PMID- 27504303
TI - Extramedullary Haematopoiesis in a Case of Pilomatricoma.
AB - Pilomatricoma is a benign follicular skin appendage tumour. It usually occurs as
solitary lesion and is most commonly seen in the face and upper extremeties. Here
we report a rare case of extramedullary haematopoiesis (EMH) in pilomatricoma in
a 38-year-old lady.
PMID- 27504304
TI - A Rare Mimicker in the Placenta.
PMID- 27504305
TI - Evaluation of Hand Written and Computerized Out-Patient Prescriptions in Urban
Part of Central Gujarat.
AB - INTRODUCTION: Prescription order is an important therapeutic transaction between
physician and patient. A good quality prescription is an extremely important
factor for minimizing errors in dispensing medication and it should be adherent
to guidelines for prescription writing for benefit of the patient. AIM: To
evaluate frequency and type of prescription errors in outpatient prescriptions
and find whether prescription writing abides with WHO standards of prescription
writing. MATERIALS AND METHODS: A cross-sectional observational study was
conducted at Anand city. Allopathic private practitioners practising at Anand
city of different specialities were included in study. Collection of
prescriptions was started a month after the consent to minimize bias in
prescription writing. The prescriptions were collected from local pharmacy stores
of Anand city over a period of six months. Prescriptions were analysed for errors
in standard information, according to WHO guide to good prescribing. STATISTICAL
ANALYSIS: Descriptive analysis was performed to estimate frequency of errors,
data were expressed as numbers and percentage. RESULTS: Total 749 (549
handwritten and 200 computerised) prescriptions were collected. Abundant omission
errors were identified in handwritten prescriptions e.g., OPD number was
mentioned in 6.19%, patient's age was mentioned in 25.50%, gender in 17.30%,
address in 9.29% and weight of patient mentioned in 11.29%, while in drug items
only 2.97% drugs were prescribed by generic name. Route and Dosage form was
mentioned in 77.35%-78.15%, dose mentioned in 47.25%, unit in 13.91%, regimens
were mentioned in 72.93% while signa (direction for drug use) in 62.35%. Total
4384 errors out of 549 handwritten prescriptions and 501 errors out of 200
computerized prescriptions were found in clinicians and patient details. While in
drug item details, total number of errors identified were 5015 and 621 in
handwritten and computerized prescriptions respectively. CONCLUSION: As compared
to handwritten prescriptions, computerized prescriptions appeared to be
associated with relatively lower rates of error. Since out-patient prescription
errors are abundant and often occur in handwritten prescriptions, prescribers
need to adapt themselves to computerized prescription order entry in their daily
practice.
PMID- 27504306
TI - A Retrospective Study of the Treatment Outcome of Drug Therapies used in Heart
Failure Patients with Associated Co-morbidities in a Tertiary Care Hospital.
AB - INTRODUCTION: Heart failure is one of the most common heart problems seen in the
Indian population. There are various drugs used to prevent further progression of
the disease. In India, there are few studies in relation to treatment outcome in
a tertiary care hospital. AIM: To study the treatment outcome of drug therapies
used in heart failure patients with associated co-morbidities in a tertiary care
hospital. MATERIALS AND METHODS: This was an observational study conducted on 250
patients with heart failure. Details collected using the proforma were demography
(age, gender); medical history; medication history for heart failure patients on
admission and discharge; ejection fraction; median length of stay in hospital;
number of readmissions & in-hospital mortality. RESULTS: One hundred and twenty
eight patients categorized into LVSD group (ejection fraction <40%) and 122
patients in PSF group (ejection fraction > 40%). Medical history of coronary
artery disease (54%) was significantly higher in LVSD group (p<0.05) and anaemia
(19%) was significantly higher in PSF group (p<0.05). On admission, inotropes
(30%), digoxin (59%) and statins (54%) were prescribed more in LVSD patients
(p<0.05) while calcium channel blockers (20%) were prescribed more in PSF group
(p<0.05). At discharge, patients with LVSD were receiving ACE inhibitors (51%),
beta blockers (30%), digoxin (67%) and statins (59%) (p<0.05) while calcium
channel blockers (20%) was prescribed more in PSF group. The median length of
stay was slightly higher in patients with PSF (7 days) as compared to LVSD (6
days). In-hospital mortality was lower in patients with PSF (6%) than patients
with LVSD (20%). The percentage of readmissions within one month was slightly
higher in patients with PSF (15%) compared to LVSD (14%). CONCLUSION: Length of
stay in hospital was 6-7 days in heart failure patients. In hospital mortality in
LVSD patients (20%) was higher compared to PSF patients (6%). A 15% heart failure
patient were readmitted within 1month of discharge.
PMID- 27504307
TI - The Zest for Patient Empowerment.
AB - Patient Empowerment (PE) can be considered as an active and self-determining role
of patient than a passive recipient of health related services. It encourages the
provider-patient relationship to blossom and helps in clearing patients' doubts,
confusion and fears to bring in clarity, relief and assurance. For the active
involvement of the patient's in own health management they need to be awakened,
motivated, educated and enlightened to enable them to exercise their rights.
Active patient involvement in the decision-making achieves favourable health
outcome. In an empowerment based approach, the focus is not on defining a
particular type of behaviour, but on how the behaviour is defined as a goal to be
achieved by a particular individual. As a result of their empowerment process,
the patients can better self-manage their illness and their lives. Thus
empowerment of the patients will positively help medical uprising of the
community by creating an educated, health aware, informed and health conscious
mass.
PMID- 27504308
TI - Preventive and Protective Effect of Nishamalaki in STZ Induced Diabetic
Complications in Wistar Rats.
AB - INTRODUCTION: Diabetes is a metabolic disease of vital health importance because
of the complications associated with it. Clinical trials and animal studies have
demonstrated the anti-hyperglycaemic effect of Nishamalaki. Present study was
planned to evaluate the protective potential of Nishamalaki on diabetic
complication in rats. AIM: To study the Nephro-protective effect and to assess
the protective potential on retinal changes of Nishamalaki in diabetic wistar
rats. MATERIALS AND METHODS: Diabetes induced with 60 mg/kg of Streptozotocin and
110 mg/kg Nicotinamide IP. Nishamalaki, a combination of Curcuma longa and
Emblica officinalis administered orally with honey. Rats divided into six groups,
control and diabetic rats with blood glucose above 250 mg/dl were divided into 5
groups. After 8 weeks test animals were treated with Nishamalaki, Enalapril and
control with saline for 30 days. Biochemical parameters measured like Serum BSL,
BUN and Creatinine and rats were observed for development of cataract. Rats
sacrificed and kidney samples were taken to examine histopathological changes.
RESULTS: Blood Urea Nitrogen and Creatinine values were significantly (p<0.01)
reduced in Nishamalaki group than control group. Nishamalaki showed the
protective effect on kidney pathology as seen on histopathology by near normal
glomerular and tubular structures. Control group showed shrunken glomerulus and
tubular vacuolations. In Nishamalaki group immature sub capsular cataract with
mild lenticular opacity were seen compared to the mature cataract with
significant lenticular opacity and corneal vascularisation in control group.
CONCLUSION: Nishamalaki showed protective effect on development of Nephrotoxicity
and it has also delayed the progression of cataract in rats.
PMID- 27504309
TI - Red Lentil Extract: Neuroprotective Effects on Perphenazine Induced Catatonia in
Rats.
AB - INTRODUCTION: Parkinsonism is a neurodegenerative disease that is defined by
certain symptoms such as muscle rigidity, impaired movement, catatonia, tremor
and disorientation of body. AIM: The aim was to investigate the effect of red
lentil extract on perphenazine-induced Catatonia in model of rat. MATERIALS AND
METHODS: This experimental study was done on 48 male albino rats (weight 180
200g) of the Sprague-Dawley strain. Animals were randomly divided into six groups
and were pre-treated with a single dose of red lentil extract (200, 400, 800 and
1000 mg/kg), most effective dose of bromocriptine (30mg/kg) and normal saline
(5ml/kg) via intraperitoneal (IP) route. perphenazine (5 mg/kg) was after 30
minutes, administered (IP) to induce catatonia. The scoring method of Morpurgo
was used to determine the muscular rigidity of animals. RESULTS: The results
showed that the 200mg/kg red lentil extract treated group had no significant
reduction in catatonic responses after perphenazine administration in comparison
with control group while the groups that received 800 and 1000mg/kg of red lentil
extract showed significant difference (p<0.05) at all the time points.
CONCLUSION: The results revealed that hydroalcoholic extract of red lentil has
protective effect on Catatonia induced by perphenazine in rats. So this extract
may be probably beneficial for catatonia in Parkinsonism.
PMID- 27504310
TI - The Portal Hypertensive Gastropathy: A Case and Review of Literature.
AB - Upper gastrointestinal bleeding is a cause of high risk for morbidity and
mortality. It has been debated in alcoholic cirrhosis, if alcohol exerts an
exclusive and causal role upon gastropathy or whether it is linked to cirrhotic
portal hypertension. The authors describe an autopsy report regarding mortality
caused by gastric bleeding in a 53-year-old patient who suffered from cirrhosis.
Literature has evidence of direct, marked damage of alcohol upon the gastric
mucosa and there is noteworthy statistical data implying the revaluation of the
pathogenesis of the bleeding.
PMID- 27504311
TI - Quality of Life in Infertile Menopausal Women; Development and Psychometric of an
Instrument.
AB - INTRODUCTION: So far few studies have been designed to evaluate the quality of
life instrument in infertile women. AIM: The present study was decided to design
a valid and reliable instrument to assess quality of life in Iranian infertile
women in postmenopausal period. MATERIALS AND METHODS: Both quantitative and
qualitative research methods were applied. The process was divided into three
main stages including: instrument development, instrument validity and instrument
reliability. Instrument development used three main steps, including determining
content domain, item generation and instrument construction. Instrument was
validated using face validity, content validity and factor analysis. Both
internal consistency and test-retest reliability methods were used to confirm the
reliability of the questionnaire. RESULTS: During content development, domain
step obtained 83 items in all demission of life in infertile women. In the
qualitative and quantitative face validity, 25 items had item impact less than
1.5 and were excluded from the questionnaire. In the content validity section, 17
items failure to obtain necessary score based on Lawshe formula, so were excluded
from the questionnaire. Overall, 8 factors were extracted by factor analysis
test. However, 67.38% of the total variance was explained by 4 factors, other 4
next factors explained the remaining 32.62% of the total variance. Totally,
34.01% of rotation variance was explained by first factor and 24.37% by second
factor. In questionnaire internal consistency, 8 items had Cronbach's alpha
0.942. CONCLUSION: Therefore, we recommend the use of present questionnaire as a
valid tool to evaluate the quality of life in infertile women during
postmenopausal period.
PMID- 27504312
TI - Standardized Patient's Views About their Role in the Teaching-Learning Process of
Undergraduate Basic Science Medical Students.
AB - INTRODUCTION: Standardized Patients (SPs) are widely used in medical education.
SPs have a number of advantages but also have certain limitations. At the
institution, SPs have been used since January 2013 for both teaching-learning and
assessment during the basic science years of the undergraduate medical program.
AIM: The present study was conducted to investigate the perception of SPs about
various aspects of the program and obtain suggestions for further improvement.
MATERIALS AND METHODS: A Focus Group Discussion (FGD) was conducted with a group
of five SPs during the second week of November 2015. Respondents were explained
the aims and objectives of the study and invited to participate. Written informed
consent was obtained. The FGD was conducted using a discussion guide and was
audio recorded. Various aspects of the SP program at the institution were
discussed. Motivation/s for joining the program and suggestions for further
improvement were obtained. Transcripts were created after listening to the
recordings and were read through multiple times. Similar responses were coded.
Items with similar codes were grouped together into themes. RESULTS: Three
respondents were female while two were male. The major advantage of SPs was their
flexibility and ability to present a standardized response to the student.
Students become familiar and comfortable with SPs. However, as a SP is simulating
an illness s/he may not always be able to do complete justice to the role. The
process used by SPs to prepare themselves to portray various diseases was
highlighted. The use of SPs both during teaching-learning and assessment was also
discussed. Some SPs are trained to provide feedback to students. Most SPs joined
the program based on invitations from their friends who were already SPs.
Challenges in recruiting SPs in a small island were discussed. Suggestions for
further improvement were obtained. CONCLUSION: The present study obtained the
perception of SPs regarding various aspects of the SP program at the institution.
The overall opinion of SPs was positive.
PMID- 27504313
TI - Surveillance of Anaemia: Mapping and Grading the High Risk Territories and
Populations.
AB - INTRODUCTION: Surveillance of anaemia is an ongoing process for assessing iron
status and anaemia prevalence among individuals and the communities they live in.
Measuring blood haemoglobin levels is the commonest method espoused worldwide for
screening individuals and populations for anaemia and iron deficiency. World
Health Organization (WHO) proposed a classification of public health significance
of anaemia in populations on the basis of prevalence estimated from blood levels
of haemoglobin. India falls under "Severe public health problem" category. An
attempt has been made to categorise "Severe public health problem" into grades of
severity that will help in prioritising the states and districts for targeted
action. AIM: To adapt the "WHO Classification of anaemia as a problem of public
health significance" and to use the same to identify and map high risk population
groups in the southern states of India. MATERIALS AND METHODS: The category of
'Severe Public Health Problem' has been graded based on prevalence of anaemia.
Secondary data published in the District Level Household and Facility Survey - 4
is analysed for five states and 1 UT (Union Territory) of southern part of India.
Choropleth Mapping was done to visually depict the intensity of anaemia problem
across the geographic territories. RESULTS: Children from 6 months to 59 months
were having highest prevalence of both, anaemia (68%) and severe anaemia (10%).
This was followed by pregnant women aged 15 to 49 years and Girl Child 6 to 9
years. Four of the Southern states of India including Andhra Pradesh, Karnataka,
Telangana and Tamil Nadu fall in the Grade 2 SPHP (Severe Public Health Problem).
CONCLUSION: The sixteen districts fall under Grade 3 Severe Public Health Problem
in the states of Andhra Pradesh, Karnataka and Telangana, require special focus
for identifying and addressing the determinants of such high prevalence of
Anaemia. These populations and territories require priority in the Government of
India's Rashtriya Bal Swasthya Karyakram (RBSK) in the National Health Mission to
address iron deficiency anaemia. The problem needs to be addressed through
dietary diversification and improved access to foods that have high levels of
bioavailable iron, including animal products apart from iron supplementation.
PMID- 27504314
TI - Perspectives and Challenges of HMIS Officials in the Implementation of Health
Management Information System (HMIS) with Reference to Maternal Health Services
in Assam.
AB - INTRODUCTION: Health Management Information System (HMIS) is one of the important
components of National Rural Health Mission (NRHM). The web portal of HMIS was
launched by the Ministry of Health and Family Welfare (MOHFW), Govt. of India
(GOI) in 21(st) Oct. 2008 to enable capturing of public health data from both
public and private institutions in rural and urban areas across the country. AIM:
The aim of the study was to assess the quality perspectives and challenges among
HMIS officials in implementing HMIS at their respective levels, i.e. district and
block level. MATERIALS AND METHODS: We conducted a pilot qualitative study in two
districts of Assam. HMIS officials working at district and block level were
interviewed in-depth with the help of a semi-structured interview schedule which
lasted from May to July 2014. RESULTS: Both HMIS and MCTS (Mother and Child
Tracking System) formats were considered useful, by the HMIS officials, for data
collection, planning at various levels, tracking maternal and neonatal deaths,
institutional deliveries. HMIS officials reported that MCTS is useful for
monitoring individual health status especially the status of the mother and child
and HMIS being helpful as a health facility monitoring tool. CONCLUSION: The
study used a small sample size, hence similar type of studies are required with
large sample size to understand the perspectives and challenges of HMIS officials
in the implementation of HMIS.
PMID- 27504315
TI - Health System Delay among the Pulmonary Tuberculosis Patients Presenting in the
DOTS Centers of Nepal.
AB - INTRODUCTION: Health system delay is the time for complete diagnosis of the
disease after patient approaches a health care provider. AIM: The study aims to
identify the characteristics and the determinants of unacceptable health system
delay (>= 7 days delay from health system) in diagnosis of new pulmonary
tuberculosis patients attending in Direct Observation Treatment Short course
(DOTS) centers of Nepal. MATERIALS AND METHODS: An analytical cross-sectional
study was conducted by administrating a structured questionnaire interview and
reviewing the medical record of the new sputum smear positive pulmonary
tuberculosis cases during January-May 2015. The generalized linear model (GLM)
was applied to control the clustering effects. Multiple logistic regressions were
performed to identify the association between variables with >= 7 days of
unacceptable health system delay. RESULTS: Of the 374 new sputum smear positive
pulmonary tuberculosis cases, the factors that were associated with unacceptable
health system delay (time >= 7 days) were doing business (adj.OR= 1.61, 95% CI:
1.22-2.11; p-value <0.001) and unemployed (adj.OR= 3.04, 95% CI: 1.53-6.04; p
value <0.001) had chances of health system delay. However, getting support from
parents (adj.OR= 0.55, 95% CI: 0.44-0.68; p-value <0.001), consultation with the
private practitioners/ pharmacists (adj.OR= 0.24, 95% CI: 0.07-0.81; p-value
0.021), visiting government health facilities (adj.OR= 0.31, 95% CI: 0.13-0.73; p
value 0.008), using X-ray (adj.OR= 0.69, 95% CI: 0.49-0.97; p-value 0.032) and
advance technologies for diagnosis of TB (adj.OR= 0.60, 95% CI: 0.39-0.94; p
value 0.024) were found contributing to reduce health system delay while
controlling socio-economic, knowledge, presence of symptoms and attitude factors.
CONCLUSION: About a quarter of new TB patients faced health system delay
problems. Socioeconomic factors, unemployment, influences the health system delay
when controlled for other covariates.
PMID- 27504316
TI - Assessment of Economic Impact Among In-Patients with Non-Communicable Diseases in
a Private Tertiary Care Hospital in Southern India.
AB - INTRODUCTION: Non-communicable diseases (NCDs) are currently responsible for
tremendous economic impact on households. AIM: This study was done to estimate
the direct, indirect and total costs incurred by households of in-patients with
non-communicable diseases admitted in a Private tertiary care hospital. MATERIALS
AND METHODS: It was a cross-sectional study conducted in a private tertiary care
hospital of Mangalore city in June 2012 by interviewing 30 patients and their
attenders using a validated interview schedule. RESULTS: Direct cost constituted
58.6% of the total expenses during the course of stay in the hospital. Mean
direct cost was more among patients with cancers (p=0.049). Indirect cost was
associated with educational status (p=0.04), occupational status (p<0.001) and
socio economic status (ses) (p<0.001) of patients. Total cost was more among
patients from upper middle ses households (p=0.012). Direct and indirect cost
constituted 5-10% each and total cost > 20% of the annual income of majority of
households. Medical insurance scheme was not availed by 26 (86.7%) patients due
to ignorance. CONCLUSION: Economic burden imposed by a single admission among
inpatients with NCDs was tremendous on their households. Hence, information on
various medical insurance schemes needs to be popularized among people to improve
its utilization. Health care providers need to introduce more financial schemes
to minimize health care costs among poor households.
PMID- 27504317
TI - Life Course Socioeconomic Transition and its Association with Early Onset Type 2
Diabetes: Protocol for a Sequential Exploratory Mixed Method Study.
AB - INTRODUCTION: The prevalence of early onset type 2 diabetes (Diabetes below the
age of 45 years) is increasing worldwide. Transition in socio-economic position
i.e. Life Course Socio-Economic Transition (LSET) - may contribute to the
development of early onset T2D through complex processes involving economic and
occupational opportunities as well as individual life style choices. AIM: To
develop and validate the life course socioeconomic transition questionnaire and
to know the association between life courses socioeconomic transition and early
onset type 2 diabetes. MATERIALS AND METHODS: This study follows sequential
exploratory mixed method study design. It consists of one qualitative strand
followed by two quantitative strands. Qualitative strand consist of in- depth
interview among the community dwellers to develop a tool for measuring LSET. Two
quantitative strands consist of the validation of the questionnaire by conducting
cross-sectional survey among 200 randomly selected community dwellers and a
hospital based case control study using the same questionnaire. RESULTS: Those
who have a history of lower SEP during his childhood period and enjoying higher
SEP during his adulthood period have an increased risk for developing type 2
diabetes at their younger age (18-45 years). CONCLUSION: This study will help to
develop a validated life course socioeconomic transition questionnaire and
application of that tool in an epidemiological study.
PMID- 27504318
TI - Parathyroid Adenoma Completely Impacted within the Thyroid Gland: A Case Report.
AB - Ectopic parathyroid adenoma can be seen in various locations. Sometimes
ultrasound and even fine needle aspiration studies cannot distinguish this lesion
from thyroid lesions. A 29-year-old woman with a prominent nodule of left thyroid
lobe was referred to surgical department. Thyroid function test were normal. She
had no family history of parathyroid disease, other endocrine disease, and any
other malignancies and had received no radiation. Ultrasonography revealed a
solid and hypoechoic mass, 25x20 mm in size, with a regular shape and contour
without calcification in the inferior of left lobe of the thyroid gland. For
definite diagnosis, immunohistochemistry study of the lesion with three markers
was done. Finally, PTH marker was positive in cytoplasms of cells so parathyroid
adenoma was confirmed. Fine needle aspiration of the nodule was suspicious for
follicular neoplasm; however, postoperative histopathology and
immunohistochemistry revealed a parathyroid adenoma. Ultrasonography may be
helpful to identify localized thyroid lesions especially in parathyroid adenoma.
PMID- 27504319
TI - Indications and Visual Outcome of Penetrating Keratoplasty in Tertiary Eye Care
Institute in Uttarakhand.
AB - INTRODUCTION: Corneal blindness forms significant proportion of visual blindness
in developing countries and penetrating keratoplasty (PK) can restore vision for
this. The prognosis of PK is dependent on the corneal diseases responsible for
corneal blindness. AIM: To evaluate the indications and visual outcome of PK in
tertiary eye care institute in Uttarakhand. MATERIALS AND METHODS: Data was
reviewed from the medical records of 145 PK done in Department of Ophthalmology,
Himalayan Institute of Medical Sciences from January 2012 to October 2014.
Analysis of data was done for evaluation of the indications and visual outcome by
Paired student's t-test for hypothesis testing of grouped values of preoperative
and last follow-up best corrected visual acuity in cases of optical and
therapeutic grafts. A p-value < 0.05 was considered statistically significant.
RESULTS: In this study data of 145 eyes of 138 patients was reviewed. The most
common indication for keratoplasty was corneal scarring including adherent
leucoma 48 (33.10%). Therapeutic keratoplasty was done for 33 cases with maximum
30(20.68%) cases of infectious keratitis. One case of tectonic graft was included
in therapeutic keratoplasty group for analysis. There was statistically
significant difference (p=.0001) in best corrected visual acuity improvement from
1.39 logMAR+ 0.022(SD) preoperatively to 0.367 logMAR+0.44(SD) postoperatively
and 1.4 logMAR+.000(SD) preoperatively to 0.16 logMAR+0.57(SD) postoperatively
for optical and therapeutic grafts respectively. CONCLUSION: Infective keratitis
either active or healed was the major indication for keratoplasty. Poor prognosis
indications were most common in this part of the country. The visual outcome
following corneal transplantation was encouraging particularly in cases of
optical keratoplasty.
PMID- 27504320
TI - Therapeutic effect of 0.1% Tacrolimus Eye Ointment in Allergic Ocular Diseases.
AB - INTRODUCTION: Allergic Ocular Diseases (AODs) like Atopic Keratoconjunctivitis
(AKC) and Vernal Keratoconjunctivitis (VKC) are chronic forms of ocular allergy
that can cause severe visual complications. Pathogenesis of AODs is uncertain and
treatment has been a challenge for ophthalmologists. Tacrolimus, a 23-member
cyclic macrolide lactone derived from [streptomyces tsukubaensis] now in ointment
form has been successfully used in AODs. AIM: To study the therapeutic effect of
0.1% Tacrolimus eye ointment in patients with Allergic Ocular Diseases (AODs).
MATERIALS AND METHODS: This prospective observational study was conducted on 36
patients with severe AOD and moderate cases not responding to conventional
treatment. They were treated with 0.1% tacrolimus eye ointment twice daily for
minimum three months in addition to conventional treatment and observed for a
period of 6 months. Symptoms and signs after treatment were evaluated. Grades of
clinical signs were assessed based on slit lamp clinical photographs; development
of possible complications was assessed and analysed by Wilcoxon signed rank test.
RESULTS: Mean age of patients was 9.3+/-4.3 years and mean duration of AODs was
3.1+/-1.8 years. The scores on both the four point scales for signs and symptoms
decreased significantly (p<0.0001) after 1 month of 0.1% Tacrolimus eye ointment
treatment. Itching was the first symptom to show dramatic relief and conjunctival
hyperaemia was the first sign to show improvement. 88.88% of patients were
successfully weaned off topical steroids in 6 months into Tacrolimus treatment.
Even in patients unresponsive to 0.1% topical Cyclosporine, symptoms and signs
scores decreased significantly (p<0.0001). The most common adverse reaction was a
transient burning sensation (36.11%). CONCLUSION: Topical 0.1% Tacrolimus eye
ointment was found to be a safe and effective treatment in cases of AODs and also
worked as steroid sparing and replacing agent. It was also found effective in
patient's refractory to topical Cyclosporine.
PMID- 27504321
TI - Mechanical Ptosis in Neurofibromatosis Type 1 Heralding the Diagnosis of Right
Sided Cervical Vagus Nerve Neurofibroma: A Rare Case Report.
AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder. In
NF1, involvement of vagus nerve can occur in the form of neurofibroma. A few
cases of neurofibroma of thoracic vagus nerve have been reported while
neurofibroma of cervical vagus nerve with NF1 is quite rare. A 19-year-old male
came with complaints of decreased vision of both eyes and right sided drooping of
eyelid since childhood. He was diagnosed as having NF1 with neurofibroma of right
cervical vagus nerve.
PMID- 27504322
TI - A Rare Case of Orbital Apex Syndrome in Herpes Zoster Ophthalmicus.
AB - Orbital Apex Syndrome (OAS) is a rare complication of Herpes Zoster Ophthalmicus
(HZO). We are reporting a case of 65-year-old male who developed OAS following
HZO. Patient presented with vesicular rash in the typical dermatomal
distribution, severe periocular congestion and limited ocular motility in all
gazes along with loss of vision. Soft tissue inflammation improved within 4 weeks
of initiation of treatment while ocular motility slowly improved over 3 months.
Patient did not gain vision despite receiving systemic steroids and systemic anti
viral medication. Variable improvement in ocular motility and visual function in
our patient points towards multiple mechanisms involved in pathogenesis of this
disease, some of which are yet to be understood.
PMID- 27504323
TI - Simple Limbal Epithelial Transplantation in Acid Injury and Severe Dry Eye.
AB - The epithelial cells of cornea constantly undergo renewal and regeneration and
the stem cells responsible for renewal resides within basal epithelium at the
limbus in palisades of Vogt. Simple limbal epithelial transplantation (SLET) is a
simplified technique for limbal stem cell deficiency and it combines the benefits
of both conjunctival limbal autografting and cultivated limbal epithelial
transplantation by being single-stage and utilizing minimal donor tissue. We will
be discussing two cases of ocular surface disorder which were managed
successfully by new technique simple limbal epithelial transplantation. Two
patients one with unilateral Limbal Stem Cell Deficiency (LSCD) following acid
injury and other with bilateral LSCD due to severe dry eye underwent limbal
epithelial transplantation using the SLET method after taking prior consent for
the procedure. Success was termed complete when a completely epithelialized,
avascular and stable corneal surface was seen. The follow up examinations were
done on first day, at 1 week, 2 weeks, 4 weeks and at 3 months after the surgery.
A completely epithelialised, avascular and stable corneal surface was achieved by
4 weeks in both patients. Simple limbal epithelial transplantation is a new
technique which is simple, cheap and easily affordable and it has decreased the
dependence on stem cell laboratory.
PMID- 27504324
TI - A Comparative Study to Assess the Determinants and Outcomes of Sepsis Treated in
Medical Wards and ICU in an Indian Teaching Hospital.
AB - INTRODUCTION: Sepsis is the primary cause of death from infection worldwide. In
resource-limited countries, increasing number of sepsis is managed in non-ICU
settings, in Medical Wards (MW). AIM: To compare the burden, aetiology and short
term outcome of sepsis treated in MW with ICU. MATERIALS AND METHODS:
Prospective, observational, analytical study in sepsis patients in general MW and
medical ICU in a tertiary care hospital. Two hundred forty five sepsis patients
(MW=150, ICU=95), >=18 years, selected randomly, were studied to compare
aetiology, co-morbidities, clinical & microbiological profile and short-term
outcome between MW and ICU sepsis. Sepsis following surgery, trauma, those
transferred to/from ICU, those with other life threatening diseases were
excluded. Chi-square test/Fisher's-exact test was used for comparing ratios. A 'p
value' <0.05 was considered statistically significant. RESULTS: Sepsis was more
common in elderly males, both in MW and ICU (median age: 56.7, 59.2 years; male:
female ratios = 1.34:1, 1.63:1 respectively). Frequency of presenting symptoms,
co-morbidities and sources of sepsis were similar in both groups (p>0.05).
Frequency of positive microbiological culture, pattern of microbial flora and
antimicrobial resistance patterns were similar in both groups (p>0.05). Number of
antibiotics used was significantly higher in ICU compared to MW (p<0.01); multi
organ dysfunction and mortality were significantly higher in ICU settings (55.8%
vs. 38.7%, p=0.04; 48.4% vs. 32.6%, p=0.041 respectively). While sepsis and
severe sepsis were significantly higher in MW (34.6% vs. 22.1 %, p=0.03; 47.3%
vs. 26.3%, p<0.01 respectively), septic shock was significantly higher in ICU
(51.6% vs. 18.0%, p<0.01). Mortality in both settings was highest in septic shock
(55.5% and 61.2%, p>0.05) and multi-organ dysfunction (55.1% and 64.2%, p>0.05).
Duration of hospital stay was significantly shorter in MW than ICU (7.3 vs. 11.0
days, p<0.01). CONCLUSION: Our study aimed to identify determinants and outcome
of sepsis in MW and compare with ICU settings. Antibiotic usage in the two
settings differed: concurrent use of >=3 antibiotics, and carbapenems & linezolid
usage were significantly higher in ICU compared to MW. Sepsis in MW had
significantly lower incidence of multi-organ failure, lower mortality and shorter
hospital stay compared to ICU.
PMID- 27504325
TI - A Prospective Study of the Clinical Profile, Outcome and Evaluation of D-dimer in
Cerebral Venous Thrombosis.
AB - INTRODUCTION: Cerebral Venous Thrombosis (CVT) is a well known disease with
diverse clinical presentation and causes. With advances in neuroimaging and
changing lifestyles, the clinical profile and causes of CVT are changing. D-dimer
has been studied in early diagnosis of CVT with variable results. This
prospective study was carried out to assess the clinical profile of CVT and role
of D-dimer in diagnosis of CVT. AIM: To study various aspects of CVT and role of
D-dimer. MATERIALS AND METHODS: The study period was September 2012 to July 2014
and included 80 imaging proven patients of CVT. We also included 39 controls for
assessing D-dimer. Data was collected according to a preformed format. D-dimer
was assessed by a rapid semi-quantitative latex agglutination assay. Discharged
patients were followed up to six months. RESULTS: Of the total 44 were women and
36 were men (F: M=1.2:1). The mean age of the patients was 29.5+/-9.68 years.
Most common clinical features were headache 77 (96.25%), papilloedema (67.5%) and
seizures 51 (63.75%). Pregnancy was the most common cause of CVT. Superior
sagittal and transverse sinuses were the most common sinuses to be affected. The
sensitivity and specificity of D-dimer for diagnosing CVT was 84.62% and 80%
respectively. The risk factors for poor prognosis were altered sensorium,
presence of sepsis, increased sinus involvement and deep sinus thrombosis.
CONCLUSION: CVT affects both sexes equally. Puerperium still contributes to
majority of the cases. Iron deficiency anaemia needs to be evaluated as a
contributing factor for incidence of CVT. D-dimer is not useful in puerperal
female with CVT. Positive D-dimer will strengthen the suspicion of CVT in
patients with acute headache followed by a neurological deficit.
PMID- 27504326
TI - En-Plaque Central Nervous System Tuberculoma - An Uncommon Entity: Clinico
Radiological Profile in a Cohort from a Tertiary Referral Centre.
AB - INTRODUCTION: Case reports pertaining to Magnetic Resonance Imaging (MRI)
diagnosis of en-plaque tuberculoma are limited. To the best of our knowledge,
descriptions about en-plaque tuberculoma are limited to few isolated case
reports. This paper comprehensively depicts the clinical and radiological
features in such patients and may serve not to miss this uncommon manifestation
of a common central nervous system infection. MATERIALS AND METHODS: A
descriptive documentation of the patient cohort with a detailed history and
neurological examination were carried out in all the patients. All underwent MRI
Brain which revealed en-plaque tuberculoma. Relevant investigations including
Cerebrospinal Fluid (CSF) were done in all patients. CSF Polymerase Chain
Reaction (PCR) was done in all. RESULTS: Eight adult patients (two women and six
men) with MRI showing en-plaque CNS tuberculoma were seen during a period of five
years. None had suffered from TB in the past nor had history of contact with
tuberculosis. All patients demonstrated extra axial dural based lesions and none
had cerebral ooedema, parenchymal lesions, mass effect or midline shift. The
lesions were located in bilateral corresponding regions in two patients and the
rest six had unilateral lesions. Seven patients had lesions located in the
supratentorial compartment; one had lesion extending to the infratentorium along
the tentorium cerebelli. Various patterns of enhancement were noted in our
patients: thin peripheral (n=3), homogenous (n=3), varied enhancement (n=1) and
open ring enhancement (n=1). CSF Polymerase Chain Reaction (PCR) was tested
positive for tuberculosis in all of our patients. CONCLUSION: While MRI provides
an understanding of the topography of the lesion, PCR helped in establishing the
diagnosis of tuberculosis in our patients. Awareness about en-plaque tuberculomas
can heighten the index of suspicion and can thus prevent aggressive surgical
resections and thereby reduce mortality and morbidity.
PMID- 27504327
TI - Study of Aplastic Anaemia with Cyclosporine in Resource Poor Setting.
AB - INTRODUCTION: Aplastic Anaemia (AA) is a syndrome characterized by peripheral
pancytopenia with hypo-cellular marrow. Acquired idiopathic AA is the most common
variety, probably of an autoimmune aetiology. Bone Marrow Transplantation (BMT)
is the treatment of choice but cost is the limiting factor. Antithymocyte
Globulin and Cyclosporine-A is an alternative to BMT. Cyclosporine alone has been
tried as a single agent in resource poor setting. AIM: The study was conducted
with the aim to observe the treatment response in aplastic anaemia to Cycloserine
A. MATERIALS AND METHODS: Patients who were diagnosed as AA and opted for
Cyclosporine with informed consent were included in the study. All the subjects
were started on 5mg/kg of Cyclosporine and were followed up for three months to
see the treatment response. This study had the approval from IEC. RESULTS: Twenty
patients were enrolled in the study. Age of the patients ranged from 10 to 65
years. Maximum number (10/20) of patients was in the 2(nd) decade. Most of the
patients presented with mucosal bleeds and breathlessness on exertion; the
predominant sign was pallor. Eleven patients had severe AA, eight had non severe
and one had very severe anaemia. Out of 20, three patients were lost to follow-up
and one patient discontinued therapy due to renal dysfunction; finally sixteen
patients' data was analysed. Out of 16 patients, 9 responded was and 7 did not
respond. Complete response was observed in three patients, partial response in
six patients. Seven patients had drug toxicity in the form of acute renal failure
and gum hypertrophy. CONCLUSION: Cyclosporine seems to be a reasonable
therapeutic option with good response rate and minimal side effects.
PMID- 27504328
TI - Fertility Desires and Intentions among People Living with HIV/AIDS (PLWHA) in
Southern India.
AB - INTRODUCTION: The desire of people living with HIV/AIDS (PLWHA) to have children
can have significant public health implications. Combination Antiretroviral
Therapy (cART) has increased the life expectancy of PLWHA as a result of which
they may consider child bearing. There are hardly any studies from India
addressing the fertility desires among PLWHA. AIM: This study was done to assess
the fertility desires of PLWHA in Southern India. MATERIALS AND METHODS: It was a
cross-sectional study conducted among 230 HIV-positive men and women who
presented to Kasturba Medical College (KMC), Mangalore, India. Study was
conducted between October 2012 and October 2014. Statistical analysis was
performed using SPSS software version 11.5. Chi-square test, Fisher's exact test
and student t-test was used to find out the association of various factors
affecting fertility desire. A p-value of less than 0.05 was considered
statistically significant. RESULTS: The mean age of our study population was
36.3+/-5.5 years. The mean age of males was 37.3+/-6 years and for female 34.9+/
5 years. In our study 132 (57.4%) were males. Majority were literate 229 (99%).
Majority of patients were employed 166 (72%). In our study 195 (84.7%) were on
cART. Out of 230 PLWHA 39 (16.95%) were unmarried and 151(65.5%) married PLHIV
were living with partners at the time of study. In our study 77 (33.5%) patients
had fertility desire. Age, gender, marital status, number of children, partner's
fertility desire and HIV status of partner had an association with fertility
desire. CONCLUSION: Providing universal access to cART is the main aim of
national programs. It is high time that these programs focus on fertility issues
of PLWHA. Reproductive rights of PLWHA need to be respected. Physicians and HIV
counselors should proactively discuss and address reproductive issues of PLWHA.
PMID- 27504329
TI - The Ultrasonographic Determination of the Position of the Mental Foramen and its
Relation to the Mandibular Premolar Teeth.
AB - INTRODUCTION: The position of the mental foramen has been well researched in
cadaver specimens, radiographically as well as intraoperatively. To our
knowledge, this landmark study is the first to make use of ultrasonography in a
study population to determine the position of the mental foramen in relation to
the mandibular premolar teeth. Ultrasonography has great potential to further
revolutionize the practice of medicine and dento-maxillofacial surgery. AIM: To
make use of ultrasound to determine the position of the mental foramen and its
relation to the mandibular premolar teeth. MATERIALS AND METHODS: One hundred
Black and Caucasian subjects were enrolled. A high frequency (8MHz) transducer
(PLF.805ST) of a diagnostic ultrasound system (model SSA-510A) was applied above
the inferior border of the mandible, just lateral to the mentum. With the marker
of the transducer pointing cranially, the position of the mental foramen in
relation to the closest mandibular premolar tooth was determined. The position
was compared across race, sex and age groups. RESULTS: All mental foramina (100%)
were visualised. Overall the most frequent position of the mental foramen was in
line with the long axis of the second premolar on the right (44%) and between the
first and second premolars on the left (44%). There were no statistical
differences (p >0.05) between race groups, sex and age groups with regard to the
position of the mental foramen in relation to the mandibular premolars. However,
in Blacks, the most frequent position of the mental foramen was in line with the
long axis of the second premolar and in Caucasians the most common position was
between the first and second premolars. The most frequent position of the mental
foramen in females was in line with the long axis of the second premolar on the
right and between the first and second premolars on the left. In males, the most
frequent position of the mental foramen was in line with the long axis of the
second premolar bilaterally. The most common position of the mental foramen in
the age group category 18-30 years was between the first and second premolars. In
patients aged 31-60 years the most frequent position was in line with the long
axis of the second premolar. CONCLUSION: Ultrasound is a sensitive modality to
locate the mental foramen. There are differences in the most common position of
the mental foramen with regard to the long axis of the premolar teeth.
Ultrasonography has the potential to revolutionize the practice of dento
maxillofacial surgery.
PMID- 27504330
TI - A Therapeutic Effects of Atorvastatin on Genetic Damage in Coronary Artery
Disease.
AB - INTRODUCTION: Coronary Artery Disease (CAD) a multifactorial chronic heart
disease and the most frequent cause of death and disabling symptoms worldwide,
occurs due to the formation of atheromatous lipid rich plaques in the arteries.
Statins, which inhibit cholesterol biosynthesis, have both pleiotropic and Low
Density Lipoprotein (LDL)-lowering properties. Atorvastatin is one of the choices
for the primary and secondary prevention of cardiovascular disease and management
of hypercholesterolaemia. However, there is a paucity of data regarding the
changes in the DNA damage in patients with coronary atherosclerosis after statin
use. AIM: The aim of the present study was to evaluate atorvastatin treatment
efficacy on lipid profiles and DNA damage in CAD patients. MATERIALS AND METHODS:
The current observational study was conducted on 180 CAD patients between
November 2011 to December 2013 at Durgabai Deshmukh Hospital and Research Centre,
Vidya Nagar, Hyderabad, India. Atorvastatin administered and blood samples were
collected at index hospitalization and after 6 months statin therapy and lipid
profiles and DNA damage was compared with 200 healthy control. RESULTS: Lipid
profiles and DNA damage were found to be significantly high (p < 0.01) in CAD
patients before atorvastatin therapy compared to after 6 months statin therapy
and healthy controls. CONCLUSION: The study suggests that atorvastatin might help
in regression of lipid profile as well as DNA damage of CAD patients.
PMID- 27504331
TI - Factors Contributing Towards Poor Asthma Control in Patients on Regular
Medication.
AB - INTRODUCTION: In-spite of the availability of effective medications, it is
observed that patients with bronchial asthma on treatment are poorly controlled.
An objective evaluation of asthma control especially with respect to inflammation
and the factors contributing towards poor control is crucial in obtaining relief
of symptoms. AIM: 1) To measure the asthma control using modified Mini Asthma
Quality Of Life Questionnaire (MAQOL) and sputum eosinophil count; 2) To identify
the role of factors viz. age, duration of asthma, severity, compliance, technique
of inhalation and knowledge of asthma action plan on asthma control. MATERIALS
AND METHODS: Total 50 asthmatic patients on regular medication were included in
the study after obtaining written informed consent. The asthma-control was
evaluated based on history, clinical symptoms, need for short-acting
bronchodilators, FEVs1 and sputum eosinophil count with the help of modified
MAQOL. A global score of <80% was considered as poor control. The proportion of
patients under each factor, in poorly-controlled group (PC) was compared with the
well-controlled group (WC). The results were analysed using descriptive
statistics and unpaired student's t-test. RESULTS: Of the total, 33 (66%)
patients were in PC category with a mean global asthma score of 58.46 +/- 2.881
vs 85.2 +/- 1.19 in the WC group (34%) (p<0.05). The mean age in PC was 41.41 +/-
2.413 vs 29.00 +/- 2.157(p<0.05) in the WC. The mean duration of asthma was 16.76
+/- 2.761 in PC vs 7.882 +/- 2.065 years in WC (p<0.05). The severity score was
7.265 +/- 0.4434 in PC vs 6.706 +/- 0.64 in WC. Eight patients in PC and six in
WC were unaware of the treatment plan. One in PC group and three in WC were
unaware of technique of inhalation. One in PC group and three in WC were non
compliant. Mean sputum eosinophil count was 7.441 +/- 1.081 in PC vs 5.176 +/-
1.201 in WC. CONCLUSION: MAQOL is useful in evaluating asthma-control. Sputum
eosinophil count correlates with asthma-control. Duration of asthma, age and
severity contributed significantly to the poor control of asthma. There is a need
for an objective monitoring in asthma and the treatment strategies need to be
modified accordingly.
PMID- 27504332
TI - Benign Recurrent Intrahepatic Cholestasis in a Young Adult.
AB - Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare genetic disorder
characterized by recurrent episodes of cholestatic jaundice. The initial episode
of jaundice generally occurs before second decade of life and can persist for
several weeks to months before resolving spontaneously. It is a benign disease
and even after repeated episodes of jaundice, fibrosis of liver cell does not
occur. We had a young adult patient who was having recurrent episodes of
cholestatic jaundice with intervening symptom free period for last 20 years. He
had first episode of jaundice at the age of eight and since then had several
similar episodes. Diagnosis was made by classical clinical presentation and
histopathological findings. We intend to report this case due to rarity of this
disease in India.
PMID- 27504333
TI - Association of Systemic Lupus Erythematosus and Beta Thalassaemia Trait- A Case
Report.
AB - Systemic Lupus Erythematosus (SLE) is a multisystem chronic inflammatory disease
of autoimmune aetiology. It has a predilection for female gender and presence of
photosensitive rash over the sun exposed area gives a clue to the diagnosis.
Diagnosis in a male patient with atypical manifestations is unusual and
difficult. A 25-year-old male presented with fever, fatigue, vomiting, abdominal
pain and loss of weight. He had sustained injury on his right arm following which
he developed abscess at the trauma site and severe anaemia. Further evaluation
revealed pancytopenia and peritonitis. Though peritonitis is rare in SLE, it was
considered in the differential diagnosis after ruling out bacterial and
tubercular peritonitis. Positive anti-dsDNA and antiSm antibodies confirmed the
diagnosis. While evaluating for microcytic anaemia it was found that iron studies
were normal and A2 fraction was raised in haemoglobin electrophoresis. The
symptoms and laboratory parameters improved remarkably with steroid therapy. Beta
thalassaemia trait is rare in patients with SLE, but when they co-exist the
manifestations can be severe. High degree of suspicion is required to diagnose
SLE in male patients in absence of typical photosensitive rash. Beta thalassaemia
trait often does not require any treatment except genetic counseling. However
empirical treatment with iron should be avoided.
PMID- 27504334
TI - Herpes Zoster Infection Involving Mandibular Division of Trigeminal Nerve and
Ramsay Hunt Syndrome with Meningitis in an Immunocompetent Patient: A Rare
Association.
AB - Herpes zoster is a unilateral painful vesicular cutaneous eruption caused by the
reactivation of the Varicella zoster virus. It commonly affects the older people
and immunocompromised individuals. The dermatomes from T3 to L3 are most
frequently involved. Its three stages include prodromal stage, active stage and
chronic stage. The common complications of the infection include post-herpetic
neuralgia, Ramsay Hunt syndrome, Guillain-Barre syndrome, transverse myelitis and
encephalomyelitis. This case report summarizes a very rare association of herpes
zoster meningitis with the involvement of mandibular division of the trigeminal
nerve and facial nerve. The patient improved with intravenous acyclovir and
prednisolone treatment.
PMID- 27504335
TI - Resistant Hypertension due to Fibromuscular Dysplasia in a Young Male: A Rare
Case Report.
AB - Fibromuscular Dysplasia (FMD) is a sporadic non-atherosclerotic disease. FMD has
been established in nearly every arterial bed. However, the most frequent
arteries affected are the renal and carotid arteries. Disease presentation may
vary broadly, depending upon the arterial bed complication and the severity of
illness. Hypertension, particularly resistant type, headache and dizziness are
the most common presentations. String of beads appearance in angiographic views
due to post-stenotic aneurysms is the characteristic view. It is most commonly
described in young aged females; but in rare male cases has also been reported.
Moreover, balloon angioplasty is standard and effective therapy for FMD. We
present a young 28-year-old man who was referred for evaluation of resistant
hypertension for nearly 3 years without comprehensive workup. The patient
underwent renal artery angiography which confirmed beading narrowing of the right
renal artery with significant stenosis at mid portion compatible with FMD; and
balloon angioplasty was done. This case highlights that FMD should be kept in
mind as a rare cause of resistant hypertension in young males; although it is
most common in young females.
PMID- 27504336
TI - ECMO Rescue Therapy in Diffuse Alveolar Haemorrhage: A Case Report with Review of
Literature.
AB - Extracorporeal Membrane Oxygenation (ECMO) has evolved as a treatment option for
patients having potentially reversible severe respiratory failure who are
deteriorating on conventional ventilation. During ECMO, systemic anticoagulation
is needed to maintain patency of the circuit. Therefore, ongoing haemorrhage
remains a relative contra-indication to ECMO as it can further increase the
bleeding. There is only limited evidence available for the use of ECMO in
patients with alveolar haemorrhage. Most of these patients did not receive any
anticoagulation during ECMO. We describe our experience with a patient who
received intravenous anticoagulation during ECMO for refractory hypoxemic
respiratory failure due to Diffuse Alveolar Haemorrhage (DAH) associated with
Granulomatosis polyangitis (Wegner's GPA). ECMO sustained life by maintaining gas
exchange support and provided the time for the immunotherapy to be effective. We
report the successful use of anticoagulation during ECMO in a patient with DAH.
PMID- 27504337
TI - Sero-Negative Systemic Sclerosis: A Rare Presentation.
AB - Systemic Sclerosis is a multisystem disease associated with progressive fibrosis
of skin and internal organs. It is diagnosed by presence of characteristic
clinical findings and is supported by specific serologic abnormalities. ANA is
positive in case of systemic sclerosis in 90 percent of cases. We report a rare
case of this rare disease where patient was ANA, Antitopoisomerase I (anti-Scl
70), Anticenteromere antibody negative.
PMID- 27504338
TI - Acute Myocardial Infarction Following Blunt Chest Trauma and Coronary Artery
Dissection.
AB - Blunt chest traumatic coronary artery dissection is an uncommon cause of
atherosclerotic and non-atherosclerotic Acute Myocardial Infarction (AMI).
Injuries of the coronary artery after blunt chest trauma are caused by different
mechanisms such as vascular spasm, dissection and intimal tear or rupture of an
existing thrombus formation. Chest pain might be masked by other injuries in
patients with multiple traumas in car accident. Present case report is on a 37
year-old male without any specific past medical history who reported to the
emergency department of a hospital with chest discomfort and was discharged with
the impression of chest wall pain. After three days he experienced severe chest
pain and he was admitted with the impression of acute coronary syndrome and
underwent coronary angiography which showed Left Anterior Descending (LAD) artery
dissection. The possibility of injury of the coronary artery should be kept in
mind after blunt trauma to the chest. This condition is sometimes underdiagnosed.
Its diagnosis may be difficult because chest pain can be interpreted as being
secondary to chest wall contusion or it may be overshadowed by other injuries.
Coronary dissection diagnosis after chest trauma requires clinical suspicion and
systematic evaluation. Electrocardiography (ECG) should be done for every patient
with thoracic trauma as the clinical findings may be misleading.
PMID- 27504339
TI - Systemic Sclerosis with Multiple Pulmonary Manifestations.
AB - Systemic sclerosis (SSc) is a chronic autoimmune multisystem disorder
characterized by endothelial dysfunction and fibroblast dysfunction, which
results in progressive fibrosis of the skin and internal organs more frequently
the lungs and gastro intestinal tract. Pulmonary involvement is common in the
course of SSc, with Interstitial Lung Disease (ILD) and Pulmonary Arterial
Hypertension (PAH) being the leading causes of death. Here we report, case of an
elderly female patient presenting with Diffuse SSc with multiple uncommon
pulmonary manifestations like ILD with Usual Interstitial Pneumonia (UIP) pattern
(usually less common), PAH and right sided pleural effusion.
PMID- 27504340
TI - Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy:
Our Experience and the Review of Literature.
AB - Metronidazole is an antimicrobial agent mainly used in the treatment of several
protozoal and anaerobic infections, additionally, is often used in hepatic
encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole
can also cause symptoms of central nervous system dysfunction like ataxic gait,
dysarthria, seizures, and encephalopathy which may result from both short term
and chronic use of this drug and is collectively termed as "metronidazole induced
encephalopathy"(MIE). Neuroimaging forms the backbone in clinching the diagnosis
of this uncommon entity, especially in cases where there is high index of
suspicion of intoxication. Although typical sites of involvement include
cerebellum, brain stem and corpus callosum, however, lesions of other sites have
also been reported. Once diagnosed, resolution of findings on Magnetic Resonance
Imaging (MRI) of the Brain along with clinical improvement remains the mainstay
of monitoring. Here we review the key clinical features and MRI findings of MIE
as reported in medical literature. We also analyze implication of use of this
drug in special situations like hepatic encephalopathy and brain abscess and
discuss our experience regarding this entity.
PMID- 27504341
TI - Differences in Bacterial Colonization and Biofilm Formation Property of
Uropathogens between the Two most Commonly used Indwelling Urinary Catheters.
AB - INTRODUCTION: Catheter Associated Urinary Tract Infections (CAUTI) are one of the
most common cause of nosocomial infections. Many bacterial species show biofilm
production, which provides survival benefit to them by providing protection from
environmental stresses and causing decreased susceptibility to antimicrobial
agents. Two most common types of catheters used in our setup are pure silicone
catheter and silicone coated latex catheter. The advantage of pure silicone
catheter for long term catheterization is well established. But there is still a
controversy about any advantage of the silicone catheter regarding bacterial
colonization rates and their biofilm production property. AIMS: The aim of our
study was to compare the bacterial colonization and the biofilm formation
property of the colonizing bacteria in patients with indwelling pure silicone and
silicone coated latex catheters. MATERIALS AND METHODS: This prospective
observational study was conducted in the Urology Department of our institute.
Patients who needed catheterization for more than 5 days during the period July
2015 to January 2016 and had sterile precatheterisation urine were included in
the study. Patients were grouped into 2 groups of 50 patients each, Group A with
the pure silicone catheter and Group B with the silicone coated latex catheter.
Urine culture was done on the 6(th) day of indwelling urinary catheter drainage.
If growth was detected, then that bacterium was tested for biofilm production
property by tissue culture plate method. STATISTICAL ANALYSIS: Statistical
analyses were performed using the Statistical Package for the Social Science
Version 22 (SPSS-22). RESULTS: After 5 days of indwelling catheterization, the
pure silicone catheter had significantly less bacterial colonization than the
silicone coated latex catheter (p-value=0.03) and the biofilm forming property of
colonizing bacteria was also significantly less in the pure silicone catheter as
compared to the silicone coated latex catheter (p-value=0.02). There were no
significant differences in the colonizing bacteria in the 2 groups. In both the
groups the most common bacteria were Escherichia coli. CONCLUSION: The pure
silicone catheter is advantageous over the silicone coated latex catheter in
terms of incidence of bacterial colonization as well as the biofilm formation and
hence in the management of CAUTI.
PMID- 27504342
TI - Total Thyroidectomy for Benign Thyroid Diseases: What is the Price to be Paid?
AB - INTRODUCTION: Total thyroidectomy has been used to treat patients with malignant
thyroid disease. But for patients with benign thyroid disease, the safety and
efficacy of total thyroidectomy is a matter of debate. Subtotal thyroidectomy
that was previously the treatment of choice for benign thyroid disease has been
associated with high recurrence rates. The risk of permanent complications is
greatly increased in patients who undergo surgery for recurrence of benign
thyroid disease. Total thyroidectomy is an operation that can be safely
performed, with low incidence of permanent complications, which allows one to
broaden its indications in various benign thyroid diseases, thus avoiding future
recurrences and reoperations. AIM: To assess the benefits of total thyroidectomy
for benign thyroid diseases. MATERIALS AND METHODS: This randomized prospective
study was conducted between Feb 2013 and Nov 2014 in the Department of General
Surgery at Bangalore Medical College and Research Institute. It included 116
patients undergoing total thyroidectomy procedure for benign thyroid disease. All
cases were followed-up for a period of 6 months for incidence of RLN palsy,
hypoparathyroidism, disease recurrence and number of incidental malignancies
detected on postoperative histological analyses of the thyroid specimens.
RESULTS: Most of the patients were in the third decade of their lives. The female
to male ratio was 6.7:1. Total thyroidectomy was done for 116 benign thyroid
diseases with multinodular goiter as the most common diagnosis. The incidence of
postoperative hypocalcaemia was 16.37% (however, only 1 patient developed
permanent hypocalcaemia) and that of wound infection was 2.58% and seroma
formation was 2.58%. None of the patients included in this study had haematoma
formation or RLN paralysis. An incidental malignancy was identified in 11.20%
patients. CONCLUSION: Total thyroidectomy shows benefits in eradicating
multinodular goiter, alleviating Grave's opthalmopathy, treating Hashimoto's
thyroiditis and preventing recurrence. It decreases the likelihood of future
operations for recurrent disease or completion thyroidectomy for incidental
thyroid cancer thus decreasing the associated risks of increased morbidity
associated with second operation. Therefore, for benign thyroid diseases
requiring surgical management total thyroidectomy can be considered the treatment
of choice.
PMID- 27504343
TI - Effect of Lump Size and Nodal Status on Prognosis in Invasive Breast Cancer:
Experience from Rural India.
AB - INTRODUCTION: Breast cancer is now the leading cause of cancer among Indian
women. Usually large tumour size and axillary lymph node involvement are linked
with adverse outcome and this notion forms the basis of screening programs i.e.
early detection. AIM: The present study was carried out to analyse relationship
between tumour size, lymph node status and there relation with outcome after
treatment. MATERIALS AND METHODS: Fifty patients with cytology-proven invasive
breast tumours were evaluated for size, clinical and pathologic characteristics
of tumour, axillary lymph node status and outcome data recorded on sequential
follow-up. RESULTS: Mean age of all participated patients was 52.24+/-10 years.
Most common tumour location was in the upper outer quadrant with mean size of
primary tumour being 3.31+/-1.80cm. On pathology number of lymph nodes examined
ranged from 10 to 24 and 72% of patients recorded presence of disease in axilla.
Significant positive correlation (p<0.013; r(2)=0.026) between tumour size and
axillary lymph node involvement on linear regression. Also an indicative
correlation between size and grade of tumour and axillary lymph node status was
found with survival from the disease. CONCLUSION: The present study highlights
that the size of the primary tumour and the number of positive lymph nodes have
an inverse linear relationship with prognosis. Despite advances in diagnostic
modalities, evolution of newer markers and genetic typing both size of tumour as
T and axillary lymphadenopathy as N form an integral part of TNM staging and are
of paramount importance for their role in treatment decisions and illustrate
prognosis in patients with invasive breast cancer.
PMID- 27504344
TI - Changing Trends of Skin Cancer: A Tertiary Care Hospital Study in Malwa Region of
Punjab.
AB - INTRODUCTION: Skin cancer constitutes a small but significant proportion of
patients with cancer. Although the presence of eumelanin in dark skin is
protective against the development of skin cancer, it is increasingly being
diagnosed in the Indian population. AIM: To study the profile of skin cancer
patients presenting to a tertiary hospital in Malwa area of Punjab, India.
MATERIALS AND METHODS: Retrospective study was done to analyse the profile of
skin cancer patients who attended the institution over one year from 1(st)
December 2013 to 30(th) November 2014. A comprehensive review of aetiology and
related risk factors was done to correlate the environmental factors with high
skin cancer prevalence in this region. RESULTS: Skin cancer constituted (3.18%)
84 out of 2638 patients registered with cancer of all types. The age of the
patients was 62+/-14.2 years and ranged from 27 to 92 yrs. Basal cell carcinoma
(BCC) was the most common histological type(46/84, 54.76%) followed by squamous
cell carcinoma (SCC) (31/84, 36.91%) and malignant melanoma (MM) (7/84, 8.33%).
Male: female ratio was found to be 0.79:1. BCC showed higher female preponderance
(p<0.05). Head and Neck was the commonest site involved (p<0.05). Majority (88%)
of patients were from rural area. 92% of patients were directly into the
profession of agriculture with history of prolonged exposure to sunlight.
CONCLUSION: Skin cancer constitutes a small but significant proportion of
patients with cancers. This study highlights a paradoxically increasing trend of
BCC and female preponderance. Head and neck is the most common site involved.
Exposure to Ultra Violet B (UVB) radiation and higher levels of arsenic in
drinking water has been reported to be associated with skin cancers. Limited
studies show that levels of arsenic and pesticides were higher in the samples of
drinking water in Malwa area of Punjab. Therefore a multipronged strategy to
provide safe drinking water supply and discouraging the indiscriminate use of
pesticides is recommended.
PMID- 27504345
TI - 'Ubiquitous' Tumour Elsewhere, But Uncommon in the Colon! Can We Ignore this
Lesion?
AB - Lipoma, a benign tumour of mature fat cells, can occur anywhere in the body and
hence termed 'ubiquitous tumour'. But it rarely occurs in the colon and can
present with complications and mimic malignancy. We present a case of descending
colonic lipoma which led to a diagnostic dilemma.
PMID- 27504346
TI - Case Report: Collision Tumour of Colon Leiomyosarcoma and Adenocarcinoma.
AB - The colon is an exceedingly rare site of primary leiomyosarcoma and only a few
cases have been published to date. Of the reported cases of collision tumours,
collision tumours that specifically occurred in the colon have consisted of
combinations of adenoma or adenocarcinoma with lymphomas or neuroendocrine
tumours. Here, not only do we report a case of colon leiomyosarcoma, but we
report, what is to our knowledge, the first case of collision tumour consisting
of colon leiomyosarcoma and adenocarcinoma. Cause, prognosis, and treatment of
colon collision tumours vary and are yet to be understood.
PMID- 27504347
TI - Scalp Haematoma in Cerebral Palsy Case due to Unknown Cause - A Rare Case Report.
AB - Incidences of cerebral palsy (CP) in children are not quite common even though it
is the most common motor disorder in children. Further quality of life in CP
cases is not so good in young adult stages and has to face certain problems.
However scalp haematoma formation in CP patient without injury to head is rarely
been reported. The case is being reported for the first time from Malaysia. We
report on a unique case of scalp haematoma in an 18-year-old girl of known CP
patient with unknown cause. No history of trauma or fall with any of the focal
neurological signs or symptoms was found. Clinical examination showed soft boggy
swelling of 8 x 10 cm size, involving most of scalp and upper face. CT - scan
showed scalp haematoma with right orbital extraconal lesion. She underwent
incision and drainage of scalp lesion; consequently around 100 ml of clotted
blood came out. At follow-up she was doing well.
PMID- 27504348
TI - Dilatation of the Proximal Cystic Duct: Is It a Variant to "Type VI" Choledochal
Cyst?
AB - Choledochal cysts are rare congenital malformations, comprising of dilatation of
the biliary tree of different localization. Classically, classification of
choledochal cysts describes five variants of the disease. Type VI choledochal
cyst is considered by many authors as the sixth variant of this classification
and is described either as a dilatation of the cystic duct or as a cystic duct
cyst. We present a rare case of cystic duct dilatation that presented with acute
cholangiopancreatitis and a clinical picture consistent of a choledochal cyst in
a 10-year-old female patient. Cholecystectomy with excision of the cystic duct
was performed. Histopathologic examination did not reveal any findings consistent
with choledochal cyst. Based on these findings we speculate that in our case the
dilatation of the cystic duct is a variant to type VI choledochal cyst, based on
the fact that no cystic-like malformation has been identified in histology. We
provide details of the pre-operative work-up and compare them with intraoperative
findings in order to increase awareness of the condition.
PMID- 27504349
TI - Diagnostic Dilemma in a Thyroid Incidentaloma: Second Primary versus Metastatic
Nodule?
AB - With the increasing use of 18F-Fluro-Deoxyglucose (FDG) Positron Emission
Tomography (PET) the number of thyroid incidentalomas is on the rise. Focal
thyroid incidentalomas identified by FDG-PET have been reported to have a high
incidence of malignancy. Neuroendocrine tumours of the thyroid are rare entities.
The most common neuroendocrine tumour of the thyroid is medullary carcinoma. A
thyroid nodule in a patient with a known neuroendocrine tumour must be
differentiated from a primary medullary carcinoma which can present as a
diagnostic challenge to the clinician. A 65-year-old female patient was referred
for thyroidectomy for a FNAC diagnosed follicular neoplasm of the left lobe of
the thyroid, detected on FDG PET follow up. She was a known case of
neuroendocrine tumour of the pancreas with no features suggestive of familial
Multiple Endocrine Neoplasia (MEN) syndrome. The patient had undergone Whipple's
procedure elsewhere, 5 years back. Following total thyroidectomy, the final
histopathology report was suggestive of a primary neuroendocrine tumour. We
present this case to highlight the clinical dilemma in diagnosing a thyroid
incidentaloma as a second primary neuroendocrine tumour versus a solitary
metastatic nodule in the background of metastatic gastroentero pancreatic
neuroendocrine tumour. Although clinically, a metastatic nodule should have been
the obvious diagnosis, the histopathological and immunohistochemical features
were in favour of a primary non-medullary Neuroendocrine Tumor (NET) of the
thyroid.
PMID- 27504350
TI - Giant Intramuscular Nodular Fasciitis Masquerading as Soft Tissue Sarcoma with
Neural Involvement - A Case Report.
AB - Nodular Fasciitis (NF) is described as a benign reactive proliferation of
myofibroblasts that occurs predominantly in the subcutaneous location. Most
commonly presents as rapidly growing swelling in the young adults, with usual
size of less than 4cm and located commonly in the extremities. We hereby report a
case of giant nodular fasciitis of 10cm diameter which presented in an unusual
location (gluteal region) and rare plane of origin (intramuscular) with unusual
symptom of sciatic nerve involvement. Because of the size, location and neural
involvement a clinical diagnosis of soft tissue sarcoma was made. After
investigating with trucut biopsy and magnetic resonance imaging, benign nature of
the lesion confirmed and treated with complete excision, carefully preserving the
sciatic nerve. This case is presented for its rarity in size, location, plane of
origin and neural compression. To the best of our knowledge this is the first
case of nodular fasciitis of 10cm size and in the gluteal muscles.
PMID- 27504351
TI - Sebaceous Gland Carcinoma of the Lower Eyelid Reconstructed with a Composite
Flap: A Case Report.
AB - Sebaceous gland carcinomas are skin adnexal tumours occurring in the periocular
region of elderly females. It is an uncommon malignancy usually involving the
upper eyelid and has an indolent course. Mainstay of treatment is surgical
excision. Here we present a case of a sebaceous gland carcinoma of the lower
eyelid for which wide local excision was done and the lower eyelid reconstructed
using a composite flap of nasal chondromucosal graft with a nasolabial flap.
PMID- 27504352
TI - First Branchial Arch Fistula: A Rarity and a Surgical Challenge.
AB - Although 2(nd) Branchial arch fistulae (from incomplete closure of Cervical sinus
of His) are well known, 1(st) arch fistulae are much rarer (<10%) and are usually
not tackled comprehensively. We present a case of a rare first branchial arch
fistula of the type II Arnot classification, which presented with two external
openings of more than 20 years duration. Patient had a successful resection of
all the concerned fistulous tract. Review of literature and the surgical
challenges of the procedure are presented herewith.
PMID- 27504353
TI - Video Assisted Thoracoscopic Surgery (VATS) for Excision of an Ectopic Anterior
Mediastinal Intra-Thymic Parathyroid Adenoma.
AB - Ectopic anterior mediastinal parathyroid adenoma is a rare cause of Primary
Hyperparathyroidism (PHPT). Imaging studies such as Technetium-99m ((99m)Tc)
sestamibi parathyroid scan along with a Single Photon Emission Computerized
Tomogram (SPECT), and contrast enhanced Computerized Tomogram (CT) of the neck
and thorax can precisely localize the ectopic mediastinal parathyroid adenoma. We
report a 40-year-old gentleman who presented with persistent pain in the right
shoulder following trivial trauma. His biochemical investigations showed an
elevated serum calcium of 11.6mg% (Normal: 8.3-10.4 mg%) along with an elevated
iPTH of 1443 pg/ml (normal: 8-70 pg/ml) which were suggestive of primary
hyperparathyroidism. The localization studies revealed an ectopic cystic
parathyroid adenoma in the anterior mediastinum that was not accessible from the
neck. He underwent a Video Assisted Thoracoscopic (VAT) excision procedure with
normalization of serum calcium and an uncomplicated recovery. The VAT approach is
a successful minimally invasive technique for mediastinal parathyroidectomy.
PMID- 27504354
TI - Successful Resuscitation of a Cardiac Arrest following Slit Neck and Carotid
Artery Injury: A Case Report.
AB - Carotid artery injuries constitute a specific and relatively small group of
vascular trauma among the traumatic injuries to neck. They have the potential of
killing the patients within minutes to hours due to haemodynamic instability if
not managed by the specialist team within time. Central Neurologic deficit from
cerebral hypoxia either resulting primarily from trauma or secondarily from
surgery is a major concern. We hereby present a case of a 22-year-old man who
presented to emergency department with alleged assault and vascular trauma to
neck in a state of cardiac arrest. On exploration patient had injuries to
external and internal carotid arteries and external jugular vein. Combined effort
of trauma team lead to successful resuscitation and saved the life of the
patient.
PMID- 27504355
TI - A Rare Case Report of Inguinal Hernia with Persistent Mullerian Duct and
Klinefelter Syndrome.
AB - Inguinal hernia in male is a common problem but having female reproductive organs
in hernial sac is rare. It occur because of failure of mullerian duct to regress
in a male fetus during embryonic development, result in a syndrome known as
Persistent Mullerian Duct Syndrome (PMDS), which is a rare entity of male
pseudohermaphroditism. We hereby present a case of 21-year-old male patient
reported with complains of cryptorchidism and inguinal hernia. Generally
diagnosis of PMDS was established during investigation like ultrasonography, MRI
for localization of undescended testis and during surgical exploration for
inguinal hernia or cryptorchidism. Our patient was operated by bilateral inguinal
incision; hernial sac contained adult size uterus fallopian tube and upper
2/3(rd) of vagina. On karyotyping it was found that he was a case of klinefelter
syndrome also. Association of PMDS with klinefelter syndrome is very rare.
PMID- 27504356
TI - Rare Undifferentiated Tumour of Thyroid: Primary Thyroid Fibrosarcoma.
AB - Primary thyroid fibrosarcoma cases are very rare. Although it is a known fact
that soft tissue sarcomas show slow growth, there have been some cases in
literature similar to our case in which there was a fast-growing tumour tissue
causing breathing and swallowing difficulties due to painless pressure. For
diagnosis, there is no specific clinical or radiological finding. We report a 67
year-old male with a mobile fast-growing mass covering almost all over the neck
that appeared 2 months prior to the admission. Laboratory findings showed that
the patient was euthyroid. Fine needle aspiration biopsy results are consistent
with suspicion of a mesenchymal, histiocytic, epithelial or lymphoid tissue
origined malignancy. Patient was taken into surgical operation. The thyroid
tissue invaded the main vascular structure, trachea and esophagus. Due to this
situation R1 resection was applied. Immunohistopathological examination showed a
conventional type of fibrosarcoma. After the surgery, radiotherapy and
chemotherapy had been planned and applied. Patients died before the radiotherapy
sessions ended. It should be kept in mind that a rapid growth in thyroid tissue
can be thyroid fibrosarcoma, there could be a rapid clinical course and poor
prognosis after operation.
PMID- 27504357
TI - Clinical Study of Endometrial Polyp and Role of Diagnostic Hysteroscopy and Blind
Avulsion of Polyp.
AB - INTRODUCTION: Endometrial polyp is one of the common causes of Abnormal Uterine
Bleeding (AUB) in the reproductive age group as well as postmenopausal age group.
AIM: To study the clinical features of endometrial polyp and the safety and
feasibility of blind polypectomy following diagnostic hysteroscopy. MATERIALS AND
METHODS: Total of 256 women who were diagnosed to have endometrial polyp by
transvaginal ultrasound and underwent diagnostic hysteroscopy and blind
polypectomy by simple avulsion in the period of January 2008 to December 2014
were included in our study. Polyp was confirmed by the histopathology. RESULTS:
The prevalence of polyp among women who underwent diagnostic hysteroscopy and
blind polypectomy was more common in the age group of 40-49years. Polyps
manifested as AUB in 45.6% of our study population. The mean size of the polyp
was not significantly different between premenopausal and postmenopausal women
and single and multiple polyps. Histopathological study of the polyp showed two
malignant polyps in our study population. Premalignant lesions i.e., endometrial
hyperplasia without atypia and with atypia was found in 33 women. There was one
uterine perforation, one cervical tear; one false passage and one patient had
mild bleeding after the procedure. In our study, in the mean follow-up period of
37.57+/-28.12 months, 3.9% (7 women) had recurrence. In the follow-up period of
16.56+/-18.96 months, 78.9% women didn't have recurrence. CONCLUSION: Diagnostic
hysteroscopy and blind polypectomy has low complication rate and recurrence rate
and technically feasible for the practicing gynaecologists which don't need much
training and is cost-effective also.
PMID- 27504358
TI - Association of Intrauterine Device (IUD) and Cervical Neoplasia - A Study in a
Poor Nigerian Population.
AB - INTRODUCTION: Intrauterine Device (IUD) is a contraceptive method used by women
of reproductive age group. However, there are conflicting reports on the
association between IUD and cervical neoplasia. These controversies may further
hamper the poor uptake of modern contraception in Nigeria. AIM: This study was
therefore aimed at evaluating the association between IUD and cervical neoplasia.
MATERIALS AND METHODS: This was a case control study in which Pap smear results
of 156 participants on IUD were compared with those of 156 non-users of modern
contraception. The participants who were found to have abnormal cervical smear
cytology results were further subjected to colposcopy. Biopsy specimens for
histology were collected from the participants with obvious cervical lesions or
those with suspicious lesions on colposcopy. The results were analysed with
descriptive and inferential statistics at 95% level of confidence. RESULTS: Seven
(4.5%) and 2(1.3%) of participants using IUD had Cervical Intraepithelial
Neoplasia (CIN) 1 and CIN 2 respectively. Also, 5(3.2%) and 1(0.6%) of non-users
of modern contraception had CIN 1 and CIN 2 respectively. The prevalence of
cervical neoplasia among all the participants was 4.8%. Although, the proportion
of women who had CIN was more among participants using IUD than non-users of
modern contraception, the difference was not statistically significant.
CONCLUSION: There was no significant association between IUD and cervical
neoplasia in this study.
PMID- 27504359
TI - Intracranial Tuberculoma Presenting as Atypical Eclampsia: A Case Report.
AB - Occurrence of eclampsia before 20 weeks of pregnancy and after 48 hours of
delivery in the absence of typical signs of hypertension and or proteinuria is
termed as atypical eclampsia. Atypical or non-classic eclampsia will have some
symptoms of eclampsia but without the usual proteinuria or hypertension. All
patients with atypical onset should undergo neurological evaluation to rule out
neurologic causes of seizures. Cerebral tuberculosis is a rare and serious form
of disease secondary to haematogenous spread of Mycobacterium tuberculosis. Here
we present a case of cerebral tuberculoma with seizures in late pregnancy
mimicking eclampsia.
PMID- 27504360
TI - Prospective Randomized Study of Oral Diazepam and Baclofen on Spasticity in
Cerebral Palsy.
AB - INTRODUCTION: Spastic cerebral palsy (CP) is the most common form of CP. Diazepam
and Baclofen are the most commonly used oral drugs to manage spasticity. Study
was designed to evaluate and compare their effects and safety in CP children.
AIM: Study was aimed to assess and compare outcome of oral Diazepam and Baclofen
in spastic cerebral palsy children in terms of extent of reduction of spasticity
and side effects profile. MATERIALS AND METHODS: Randomized prospective follow-up
study was done for one year after giving Diazepam and Baclofen in weekly
incremental doses upto recommended maximum dose to 60 children for three months.
Two primary outcome measures were spasticity reduction and adverse effect
profile. Spasticity reduction was measured by Modified Ashworth's Scale (MAS) and
Range of Motion improvement (ROM). RESULTS: After random allocation, there was no
baseline difference between groups. Mean MAS score improved from 1.96+/-0.4 at
baseline to 1.63+/-0.40 and 1.41+/- 0.36 at 1 month and 3 months for Diazepam and
from 1.84+/-0.64 to 1.57+/-0.59 and 1.31+/- 0.48 respectively for Baclofen.
Within the group reduction was significant with p-value = 0.0001. Intergroup
comparison showed no statistically significant difference with p-value of 0.48
and 0.22 at 1 and 3 months. Baseline ROM showed significant improvement at 1 and
3 months with p value of 0.004 and 0.001 for Diazepam and 0.01 and 0.000 for
Baclofen respectively with no statistically significant difference among two
groups. Drowsiness was most common observed side effect in both the groups.
CONCLUSION: Patients showed significant improvement in spasticity as measured by
Mean MAS score and range of motion in Diazepam as well as Baclofen group. Both
drugs were found safe for use in children. Study couldn't establish any
difference between the two drugs. However studies with bigger sample size and
longer follow- up assessing functional improvement in patients will be required
in near future.
PMID- 27504361
TI - The Effect of Some Polymorphisms in Vitamin D Receptor Gene in Menopausal Women
with Osteoporosis.
AB - INTRODUCTION: Vitamin D receptor gene is one of candidate genes related to
osteoporosis expansion. The association of ApaI, TaqI, BsmI polymorphisms in
vitamin D receptor gene with bone metabolism and density has been area of
interest in many studies. AIM: This study was conducted to further investigate
the association between the ApaI, TaqI, BsmI polymorphisms and bone density. This
study was analytical study. Centers for bone density measurement in southwestern
Iran. MATERIALS AND METHODS: In this analytical study, 200 participants aged 45-
and above 45-year-old women referring the centers of bone density measurement
participated. The bone density of femoral neck and lumbar vertebrae was measured
using dual-energy X-ray absorptiometry method. Based on t-score, the participants
were assigned into patients (n=130) and healthy individuals (n=70). Different
genotypes of ApaI (AA/Aa/aa), TaqI (TT/Tt/tt), and BsmI (BB/Bb/bb) were
determined by PCR-RFLP. The data on bone density and PCR-RFLP were analysed by
chi-square and ANOVA. Also, triad combination of the genotypes was statistically
analysed. For each genotype combination, chi-square was run between the patients
and control group and p-value was calculated. RESULTS: No significant association
was seen between ApaI polymorphism and bone density (p>0.05). TaqI and BsmI
polymorphisms had a significant association with femoral neck's bone density
(p<0.05), but these polymorphisms were not significantly associated with lumbar
vertebrae's (p>0.05). Patients with homozygous dominant TT genotype had the least
bone density in femoral neck compared to other genotypes. Lumbar vertebrae's bone
density was similar in three TaqI genotypes. The patients with homozygous
recessive bb genotype had the least bone density in femoral neck and lumbar
vertebrae compared to other genotypes. CONCLUSION: TaqI and BsmI polymorphisms
could be desirable markers in diagnosis of women at risk of osteoporosis in the
studied region in Iran. Therefore, these women will receive suitable medical
treatment at proper time.
PMID- 27504362
TI - An Innovative Method of Assessing the Mechanical Axis Deviation in the Lower Limb
in Standing Position.
AB - INTRODUCTION: Various methods of measuring mechanical axis deviation of lower
limb have been described including radiographic and CT scanogram, intraoperative
fluoroscopy with the use of an electrocautery cord. These methods determine the
mechanical axis in a supine, non-weight bearing position. Although long cassette
standing radiographic view is used for the purpose but is not available at most
centres. A dynamic method of determining the mechanical axis in a weight bearing
position was devised in this study. AIM: The aim of the study was to describe a
simpler and newer method in quantifying the mechanical axis deviation in places
where full length cassettes for standing X rays are not available. MATERIALS AND
METHODS: A pilot study was conducted on 15 patients. The deviation from the
mechanical axis was measured using a manually operated, hydraulic mechanism
based, elevating scissor lift table. Patient was asked to stand erect over the
elevating lift table with both patellae facing forward and C-arm image
intensifier was positioned horizontally. Radiological markers were tied to a
radio-opaque thread and placed at the centre of head of the femur and another at
the centre of the tibio-talar joint. C-arm views of the hip, ankle and knee joint
were taken to confirm the correct position of the marker by varying the height of
the lift table. RESULTS: The mechanical axis deviation values were recorded by
measuring distance between the centre of the knee and radio-opaque thread in cm.
This was measured in each case both clinically and from the image on the monitor.
The two values were found to be statistically same. Pain was measured on VAS.
Mechanical axis deviation values and VAS score were found to be positively
significantly correlated. CONCLUSION: This technique is dynamic, unique and
accurate as compared to other methods for assessing mechanical axis deviation in
a weight bearing position.
PMID- 27504363
TI - Solitary Fibrous Tumour of the Clavicle: A Rare Case Report.
AB - A Solitary Fibrous Tumour (SFT) is the preferred term by most of the pathologists
than "haemangiopericytoma". SFT is a heterogeneous group of benign and malignant
neoplasms along a morphologic continuum. Here we report a case of SFT of the
clavicle in a 26-year-old male patient, who presented to us with complaints of
pain and swelling over the dominant shoulder. No signs of metastasis were noted
clinically and radiologically. He underwent surgical resection of swelling. At 6
months after resection and after 22 cycles of radiotherapy, he was noted to have
excellent prognosis with satisfactory shoulder function.
PMID- 27504364
TI - Deep Soft Tissue Leiomyoma of Forearm: A Case Report and Review of Literature.
AB - Leiomyomas are benign tumours of smooth-muscle origin representing 4.4% of all
benign soft-tissue neoplasms. They are classified as cutaneous, vascular and
leiomyomas of deep soft tissues. Leiomyomas rarely occur in extremities and are
more common in the lower limb than in the upper extremity. Deep soft tissue
leiomyomas are even rare with a very few reported cases so far in the literature.
A 25-year-old female presented to us with an atraumatic slowly enlarging mass in
the right forearm from 6 months with mild erosion of cortex of radius. She was
otherwise healthy, MRI revealed a soft tissue lesion involving the interosseous
space, isointense on T1, slightly hyperintense on T2 and hyperintense on STIR
images. The tumour was excised intoto. The case is presented due to its rarity
and the risk of tumor misdiagnosis. It should be considered in the differential
diagnosis of any solitary painful slow growing mass of the extremities. If
adequate margins are obtained recurrence of this tumour is very rare.
PMID- 27504365
TI - Bilateral Clavicle Fractures: A Report of Three Cases.
AB - Bilateral clavicle fractures are uncommonly reported in the literature with the
incidence being less than 0.5% of all the clavicle fractures. Bilateral clavicle
fractures are caused either by high-energy transfer of compression forces across
both shoulder girdles or by a direct trauma to one clavicle followed by that to
the other clavicle. These fractures could be missed due to their association with
more severe chest injuries or a more symptomatically displaced fracture on one
side or due to inadequate chest radiographs. We report three cases of traumatic
bilateral clavicle fractures with three modes of injuries in different age
groups. All the fractures were treated conservatively with good functional
outcomes without any sequelae. Bilateral clavicle fractures should be actively
sought by every trauma team with proper clinical examination and chest
radiographs including both shoulder joints in high-energy trauma cases or with
bilateral shoulder compression injuries.
PMID- 27504366
TI - Skeletal Maturation and Mineralisation of Children with Moderate to Severe
Spastic Quadriplegia.
AB - INTRODUCTION: Diminished bone mineral density and delayed skeletal maturation are
common in children with spastic quadriplegia. AIM: The purpose of our study was
to evaluate the Bone Mineral Density (BMD) of children with moderate to severe
spastic quadriplegia and its relationship with other variables like nutrition and
growth. MATERIALS AND METHODS: This was a hospital based, cross- sectional, case
control study. Forty-two (28 males, 14 females) children with spastic
quadriplegia and 42 (24 males, 18 females) healthy children were included in the
study. BMD of cases and control were measured by Dual Energy X-ray Absorptiometry
(DEXA). Radiographs of left hand and wrist of cases and controls were taken and
bone age was determined. RESULTS: BMD values of upper extremity, lower extremity,
thoraco-lumbar spine and pelvis in cases were lower than those of controls (p
<0.0001). In children with non severe malnutrition, 75% of the cases had lower
bone age than chronological age, whereas all cases with severe malnutrition had
lower bone age than chronological age. Step wise regression analysis showed that
nutritional status independently contributed to lower BMD values but the BMD
values did not correlate significantly with the use of anticonvulsant drugs and
presence of physical therapy. CONCLUSION: Decreased BMD and delayed bone age is
prevalent in children with spastic quadriplegia and nutritional status is an
important contributing factor.
PMID- 27504367
TI - Ventilator-Associated Pneumonia: Incidence, Risk Factors and Outcome in
Paediatric Intensive Care Units at Cairo University Hospital.
AB - INTRODUCTION: Ventilator-Associated Pneumonia (VAP) is a major cause of hospital
morbidity, mortality and increased health care costs. Although the epidemiology,
pathogenesis and outcome of VAP are well described in adults; few data exist
regarding VAP in paediatric patients, especially in developing countries. AIM: To
determine the incidence, risk factors and outcome of VAP in two Paediatric
Intensive Care Units (PICUs) at Cairo University Hospital. MATERIALS AND METHODS:
A total of 427 patients who received Mechanical Ventilation (MV) were included in
this prospective study during the period from September 2014 till September 2015.
Patients were observed daily till VAP occurrence, discharge from the unit or
death, whichever came first. Demographic, clinical characteristics, laboratory
results, radiographic and microbiological reports were recorded for all patients.
RESULTS: Nearly 31% patients developed VAP among the entire cohort. The incidence
density was 21.3 per 1000 ventilator days. The most frequently isolated organisms
from VAP patients were Pseudomonas aeruginosa (47.7%), Acinetobacter (18.2%) and
Methicillin-resistant Staphylococcus aureus (MRSA) (14.4%). VAP patients were
significantly younger than non-VAP ones. The incidence of VAP in comatose
patients and those with MOSF was significantly higher. Prior antibiotic use for >
48 h before MV, supine body positioning and reintubation were significantly
associated with VAP. On multiple logistic regression analysis, MOSF; prior
antibiotic use > 48h; reintubation; coma; and age remained independent predictors
of VAP. Mortality rate among the VAP group was significantly higher compared to
the non-VAP one (68.2% vs. 48.5%, p<0.001). Survival curve analysis showed a
shorter median survival time in VAP patients. CONCLUSION: Identification of risk
factors and outcome of VAP in PICUs may help in reducing the incidence and
improving patients' outcomes. The incidence of VAP in this study was relatively
high. The most prominent risk factors for occurrence of VAP were MOSF, prior
antibiotic use for > 48 h before MV, reintubation, coma and age. Proper use of
antibiotics before MV in PICUs is essential. Also, adequate training of nurses
and strict supervision of infection control protocols are crucial. Lack of a gold
standard for the diagnosis of VAP and difficulty in sampling procedures were
among the study limitations.
PMID- 27504369
TI - A Case Report of Childhood Recurrent Autoimmune Pancreatitis: A Rare Emerging
Entity.
AB - Autoimmune pancreatitis (AIP) is a rare entity in the paediatric population and
its aetiology is unknown. Here, we report a 10-year-old girl with recurrent
abdominal pain. A diagnosis of AIP was made based on elevated pancreatic enzymes,
elevated IgG 4 and image findings. She responded to corticosteroid treatment. AIP
should be considered in the differential diagnosis of recurrent pancreatitis.
Correct diagnosis can help avert the consequences of progressive disease and
unnecessary surgery.
PMID- 27504368
TI - Predictors of Mortality in Paediatric Myocarditis.
AB - INTRODUCTION: Paediatric myocarditis can present as mild flu like symptoms to
fulminent form. Early identification of the severity of illness and
prioritization of intensive care is helpful especially in developing countries
with limited resources. AIM: To know the factors at admission that can predict
mortality in paediatric myocarditis. MATERIALS AND METHODS: This was an
observational study which enrolled children who presented with fever of acute
onset (less than 15 days in duration), and were diagnosed as suspected
myocarditis on the basis of clinical features, Troponin I and echocardiography,
according to Expanded criteria for myocarditis in Paediatric ward at our
institute over a period from August 2014 to December 2015. Their clinical
features, cardiac biomarkers and echocardiography findings were compared between
survivors and non-survivors. STATISTICAL ANALYSIS: All statistical analysis was
done using graphpad Prism 5 and SPSS statistical software. A Fisher exact p-value
<0.05 was regarded as significant. Multivariate Logistic Regression was carried
out to quantify the relationship between cardiac death and other predictor
variables. The logistic coefficients for the predictor variables and their
exponents, that is, log odds were calculated. Statistical significance of these
predictor variables was interpreted by p-values. RESULTS: A 17.7% (n=11/62)
patients of paediatric myocarditis died in this study. New York Heart Association
(NYHA) class IV dyspnea (p=0.0115) and hypotension (p=0.0174) were more in
patients who did not survive. The mean value of Troponin I was more in the non
survivor group (0.958 +/- 1.13ng/ml); (p=0.0074). More number of patients who
died had Brain Natriuretic Peptide (BNP) levels increased in their plasma
(p=0.0087) with higher mean value (p=0.0175). LV ejection fraction was decreased
markedly in non survivor group with mean value of 37+/-8.09 % as compared to
survivor group with mean value of 46.6+/-10.5%, (p=0.0115). On multivariate
analysis, NYHA class IV dyspnea (p=0.0113), BNP (p=0.015) and ejection fraction
(p = 0.0284) independently are the predictors of mortality in our study group.
CONCLUSION: Children with myocarditis having hypotension, raised Troponin I, BNP
and decreased ejection fraction are more prone to die. NYHA IV dyspnea, higher
levels of BNP and decreased EF are independently related to worst outcome.
PMID- 27504370
TI - Eosinophilia in an Acutely Limping Child: An Easy Guess of Rare Systemic
Aetiology!
AB - Painful limping child is often considered due to septic arthritis. Iliopsoas
abscess (IPA) is rare in adults and children. The aetiology is often related to
tuberculosis of spine. Hereby we report a case of staphylococcal IPA where
incidental evaluations led to obvious diagnosis of a rare primary
immunodeficiency syndrome called Job syndrome or hyperimmunoglobulin E and
Eosinophilia Syndrome (HIES). This was the first case of IPA in a case of
immunodeficiency syndrome including HIES.
PMID- 27504371
TI - Asplenia Syndrome in a Neonate: A Case Report.
AB - Asplenia syndrome is a syndrome of right isomerism or attempted bilateral right
sidedness. It includes congenital asplenia in association with complex congenital
cyanotic heart disease and situs anomalies of the other thoracoabdominal organs.
Herein we report a case of asplenia syndrome so as to highlight and refocus
attention on the possibility of this rare syndrome that must be considered in a
neonate presenting with congenital cyanotic heart disease.
PMID- 27504372
TI - Congenital Ichthyosis - Collodion Baby Case Report.
PMID- 27504373
TI - Prevalence of Nosocominal Toxigenic Clostridium difficile in Children Under 5
Years in Hajar Hospital, Shahrekord, Iran.
PMID- 27504374
TI - Spectrum of Renal and Urinary Tract Diseases in Kashmiri Children.
AB - INTRODUCTION: Definite paucity of data pertaining to spectrum of renal and
urinary tract diseases in our state and in various parts of India forms the basis
of this study. Available data has emphasized more on specific clinical syndromes
and chronic renal diseases rather than over all spectrums of renal and urinary
tract diseases, that too in adult population. AIM: The present study a
retrospective analysis, forms one of the basic data of paediatric nephrology and
urology related disorders in our state. MATERIALS AND METHODS: Retrospective
analysis of the case records of all the hospitalized patients with renal and
urinary tract diseases between 2012 and 2013 were performed. Case records were
analysed and categorized into various groups like; Urinary Tract Infections
(UTI), Acute Kidney Injury (AKI), Acute Glomerulonephritis (AGN), Nephrotic
Syndrome (NS), haematuria, Polycystic Kidney Disease (PCKD), Posterior Urethral
Valve (PUV), Vesicoureteric Reflux (VUR), Chronic Kidney Disease (CKD),
Congenital Anomalies of Kidney and Urinary Iract (CAKUT) and others. These groups
were divided into subgroups to get more insight about the pattern of these
diseases. RESULTS: Out of 28114 patients hospitalized between 2012 and 2013
years, 447 (232 males and 215 females) patients were diagnosed of renal and
urinary tract diseases which forms 1.58% the total admitted patients. Among these
patients 32.9% (147/447) were diagnosed Acute Kidney Injury (AKI); 24.1%
(108/447): Urinary Tract Infection (UTI); 9.6% (43/447): Acute Glomerulonephritis
(AGN); 5.6% (25/447): bilateral hydronephrosis with UTI; 4.47% (20/447):
nephrotic syndrome (NS); 3.5% (16/447): haematuria; and 4% (18/447) were having
CAKUT (Congenital Anomalies Of Kidney And Urinary Tract). In addition to this
there were 17 cases of Renal Tubular Acidosis (RTA), 3 cases of Barter syndrome
and one case of Liddle syndrome. CONCLUSION: A substantial number of children are
hospitalized with renal and urinary tract diseases with delayed ages of
presentation, which at times have suffered irreversible renal damage that could
have been prevented or treated if diagnosed earlier. Our study indicates that
majority of these renal and urinary tract diseases are preventable and treatable.
Henceforth, there is a need to develop a comprehensive service for the children
with renal and urinary tract diseases in Jammu & Kashmir (J&K) India.
PMID- 27504375
TI - Accuracy of MRI in Prediction of Tumour Thickness and Nodal Stage in Oral Tongue
and Gingivobuccal Cancer With Clinical Correlation and Staging.
AB - INTRODUCTION: Squamous cell carcinoma of lower gingivo-buccal complex and tongue
are the most common cancer in the Indian sub-continent. The value of imaging in
the staging of Oral Squamous Cell Carcinoma (OSCC) is in judging operability,
assessment of the prognostic characteristics and dimensions of the primary
tumour, depth of tumour invasion, the presence of cervical metastasis and
detection of bone infiltration. AIM: This study evaluated squamous cell
carcinomas of the oral cavity (tongue and gingivo-buccal complex) on the basis of
their appearance, soft tissue extent, depth of tumour invasion and staging.
Further, this study assessed the accuracy of MRI in the detection of cervical
lymph nodal metastasis on the basis of ADC values on diffusion weighted MR
sequence. MATERIALS AND METHODS: T1- and T2-weighted MR, diffusion-weighted
sequences and post contrast T1W sequences were performed in various planes on
biopsy proven squamous cell carcinomas (61 cases) involving tongue and/or gingivo
buccal region. Depth of tumour invasion was calculated on axial images of post
contrast T1W images. The Apparent Diffusion Coefficient (ADC) was measured by
using two b factors (500 and 1000 s/mm(2)). MRI findings were compared clinically
and histopathologically. RESULTS: Average depth of invasion calculated on MRI was
8.47mm and by histopathology was 6.85mm. Pearson's correlation coefficient was
0.988. Shrinkage factor was 0.8. A 71% of patients with depth of invasion greater
than 9mm showed evidence of cervical lymph nodal metastasis at one or another
levels. Cut-off value to discriminate between malignant and benign lymph nodes
was 1.038 x10-3 mm(2)/s in the present study. CONCLUSION: Depth of tumour
invasion in oral malignancies can be measured reliably on MRI which helps in
predicting cervical lymph node metastasis. Benign or malignant cervical lymph
nodes can be differentiated on diffusion-weighted imaging of MRI on the basis of
their ADC values.
PMID- 27504376
TI - CT Evaluation of Acute Pancreatitis and its Prognostic Correlation with CT
Severity Index.
AB - INTRODUCTION: Pancreatitis is one of most complex and clinically challenging of
all abdominal disorders. USG and abdominal CT are the most commonly used
diagnostic imaging modalities for the evaluation of pancreas. Computed Tomography
(CT) is highly accurate and sensitive than USG in both diagnosing as well as
demonstrating the extent. Early assessment of the cause and severity of acute
pancreatitis is of utmost importance for prompt treatment and close monitoring of
patient with severe disease. CT is the imaging method of choice for assessing the
extent of acute pancreatitis and for evaluating complications. AIM: To assess
prognostic correlation and clinical outcome of acute pancreatitis on the basis of
CT severity index. MATERIALS AND METHODS: A prospective study of 50 cases was
carried out in the Department of Radio Diagnosis, with complaint suggestive of
acute pancreatitis on the basis of clinical/laboratory/ultrasonography findings
were evaluated in Siemens somatom 40 slice CT. The severity of pancreatitis was
scored using CT severity index, modified severity index and revised Atlanta
classification and classified into mild, moderate, severe categories. Clinical
follow-up of the patients was done in terms of the following parameters: Length
of hospital stay, Need for surgery or percutaneous intervention, Evidence of
infection in any organ system, Occurrence of organ failure- respiratory,
cardiovascular, renal, hepatic and haematological system, death. The clinical
outcome was compared with the currently accepted Balthazar's CTSI and Modified
Mortele's CTSI and revised Atlanta classification in all the cases. RESULTS: Gall
stone disease was most common aetiological factor seen in 40% cases, it was more
common in females than males. Alcohol was second most common aetiological factor
seen in 38% cases and was noted only in males. Pleural effusion was the most
common extra-pancreatic complication seen in 46% cases. Balthazar grade C was the
most common (40%) followed by grade D and E (25% each). Acute peri-pancreatic
collection was the most common findings seen in 72% cases. Majority of the cases
(42%) were categorized as mild pancreatitis according Balthazar CTSI score.
Majority of the cases (44%) were categorized as severe pancreatitis according
modified CTSI. Majority of the cases were categorized as mild pancreatitis
according revised Atlanta classification. Organ system failure, death were more
seen in severe grade in modified CTSI and revised Atlanta classification.
CONCLUSION: Modified CT severity index makes the score easier to calculate and
reduces the inter-observer variation. Scores obtained with the modified Mortele
index, show a stronger statistical correlation for all clinical outcome
parameters in all the patients better than the Balthazar index.
PMID- 27504377
TI - Wine Glass Sign and Empty Delta Sign: A Rare Imaging Presentation of Postpartum
Encephalopathy in Dehydration.
AB - Rapid correction of hyponatremia is a well-known cause of central pontine and
extrapontine myelinolysis. But uncommonly seen and rarely reported in
Hypernatraemia. We report a rare case presenting as postpartum psychosis, wherein
imaging revealed myelinolysis of corticospinal tracts in wine glass distribution
and empty delta sign due to cortical venous thrombosis. At follow-up 3 months
later, revealed significant neurological improvement. Concurrance occurrence of
this dual pathology is not been described, which in our case was due to high
serum sodium levels at presentation and dehydration.
PMID- 27504378
TI - Superior Mesentric Artery Syndrome in a Patient with Subacute Intestinal
Obstruction: A Case Report.
AB - Superior Mesenteric Artery (SMA) syndrome is one of the rare cause of proximal
small bowel obstruction wherein, the third part of the duodenum is compressed
between the SMA at its origin and abdominal aorta due to decreased angulations in
these two vessels. This decreased angulation exerts a compression effect on third
part of the duodenum, resulting in duodenal obstruction which may be complete or
partial. There are number of causes which can lead to this entity and will be
discussed briefly. Here we report imaging findings of such a rare cause of
proximal small bowel obstruction in a young male patient who presented to the
emergency surgical department with non specific symptoms of pain abdomen and
abdominal fullness. Patient was evaluated under the standard protocol in
management of abdominal pain. General physical examination, erect and supine
radiograph were taken. On barium meal follow-through examination, there was
paucity of contrast agent distal to the second part of duodenum with proximal
dilation of stomach, first and second part of duodenum which raised us the
possibility of SMA syndrome. Reconstructed CECT abdomen confirmed the decreased
angulation between SMA and abdominal aorta and diagnosed it as SMA syndrome.
Findings were correlated on duodenojejunostomy anastomotic surgical procedure.
Diagnosing and reporting such a case of SMA syndrome is of utmost importance
because the clinical presentation being non-specific pertaining to small bowel
obstruction which may pose a diagnostic difficulty to the surgeon and with the
further delay in diagnosis, patients may end up with chronic symptoms and
complications of the disease, repeated hospital visits and electrolyte
abnormalities.
PMID- 27504379
TI - Cardiac Pseudoaneurysm- A Death Defying Entity.
AB - A pseudoaneurysm refers to a contained rupture of the myocardium with a tenuous
pericardium walling off the leak. It needs to be differentiated from a true
aneurysm by the fact that there is lack of myocardial tissue in the wall of a
pseudoaneurysm. The differentiation between the two is pertinent as true
aneurysms can be treated medically while pseudoaneurysms require urgent surgical
treatment. Untreated pseudoaneurysms carry a high risk of rupture and mortality.
We report a case of cardiac pseudoaneurysm developing in a 46-year-old male who
had suffered myocardial infarction four months back. The patient now presented
with chest pain and dyspnoea. CECT chest revealed a partially thrombosed large
pseudoaneurysm arising from the posterior wall of left ventricle. While the
clinical diagnosis of this entity is difficult, CECT plays a pivotal role in the
non-invasive detection of pseudoaneurysms.
PMID- 27504380
TI - Fetal MR Imaging Analysis of Sirenomelia with Clinico Radiographic Correlation: A
Case Report.
AB - Sirenomelia is a social curiosity, a medical and diagnostic challenge prenatally
compounded by varied diagnostic difficulties. Prenatal diagnosis of sirenomelia
was and continues to be a challenge although von klippel et al., described a case
at 10 weeks of gestational age. However, they needed a second imaging at 12(th)
week for confirmation. First trimester or early second trimester anatomic survey
on ultrasound and MRI is accurate for the diagnosis thereby avoiding unnecessary
complex pregnancy. We report a case of second trimester diagnosed sirenomelia,
with detailed analysis of image findings on ultrasound and fetal MRI.
PMID- 27504381
TI - Illustrated Imaging Essay on Congenital Heart Diseases: Multimodality Approach
Part II: Acyanotic Congenital Heart Disease and Extracardiac Abnormalities.
AB - Acyanotic heart disease constitutes a significant majority of patient who may
present with non-cardiac symptoms. Either they are detected incidentally or
present with respiratory complaints. Equipped with knowledge of anatomy by
echocardiography and radiographic methods described in previous part of this
presentation, diagnosis may be confidently attempted. On plain radiography
acyanotic congenital heart diseases have variable appearance depending upon
severity of disease. Cardiac size, chamber enlargement and pulmonary vascular
pattern are key elements. Typically left to right shunts with large volume flow
are associated with pulmonary plethora. Plain radiography has an important role
in detecting manifestation of pulmonary arterial hypertension. Severe stenosis of
pulmonary valve is associated with pulmonary oligemia. Small intra-cardiac shunts
and anomalies of coronary arteries generally present with normal cardiac size and
pulmonary arterial pattern. Disease spectrum presented in this illustration
demands thorough scrutiny of pulmonary, osseous and abdominal abnormalities. This
section illustrates some commonly encountered spectrum of acyanotic cardiac
disease.
PMID- 27504382
TI - Comparison of Albumin, Hydroxyethyl Starch and Ringer Lactate Solution as Priming
Fluid for Cardiopulmonary Bypass in Paediatric Cardiac Surgery.
AB - INTRODUCTION: In paediatric cardiac surgery, there is still not any information
with regard to the best choice of priming fluids for Cardiopulmonary Bypass
(CPB). Albumin, Hydroxyethyl Starch (HES) & ringer lactate are equally used, but
each has its advantages & disadvantages. Albumin & HES had better fluid balance
which affect outcome in paediatric cardiac surgery significantly. AIM: To compare
priming solution containing albumin, hydroxyethyl starch and ringer lactate
during elective open-heart surgery in paediatrics aged up to 3 years. MATERIALS
AND METHODS: All patients were managed by standardized institution protocol and
were randomly distributed into three groups based on the priming solution which
is used in the CPB Circuit and having 35 patients in each group. Group A: Receive
albumin 10 ml/kg in priming solution, Group B: Receive Hydroxyethyl starch
(HES130/0.4) 6% 20ml/kg in priming solution, Group C: Receive ringer lactate
priming solution. Primary outcome variable included perioperative haemoglobin,
total protein, colloid osmotic pressure, platelets, fluid balance, urine output,
post-operative blood loss, blood products usage, renal & liver function,
extubation time, ICU stay & outcome. RESULTS: Patients receiving albumin had
higher perioperative platelet count, total protein level & colloid osmotic
pressure, lesser post-operative blood loss & blood products requirement. Patients
receiving HES had lower level of platelets postoperatively than ringer lactate
group but not associated with increase blood loss. HES did not affect renal
function & haemostasis in this dose. Patients receiving ringer lactate had
positive fluid balance intraoperatively. All three groups have similar effect on
renal & liver function, urine output, time to extubation, ICU stay & outcome.
CONCLUSION: We conclude that albumin is expensive but better prime as maintain
haemostasis, colloid oncotic pressure & reduced blood product requirement. HES
will not hamper haemostasis & renal function in lower dose & better than
crystalloid as maintain negative fluid balance. Patient outcome & ICU stay was
similarly affected by priming solutions.
PMID- 27504383
TI - Transdermal Buprenorphine Patches for Postoperative Pain Control in Abdominal
Surgery.
AB - INTRODUCTION: Buprenorphine is a semi-synthetic derivative of thebaine; its low
concentration is sufficient to provide effective pain relief. AIM: To evaluate
the efficacy of transdermal buprenorphine patch in postoperative pain management.
MATERIALS AND METHODS: After ethical approval and taking informed consent from
the patients, they were randomized into three groups (n=30 in each group) using a
computer generated random number table. Group A: placebo patch; Group B:
buprenorphine (10mg) patch and Group C: buprenorphine (20mg) patch. Haemodynamic
and analgesic effects were compared by using analysis of variance (ANOVA)
followed by Turkey's post hoc test. The proportion of side effects was compared
using the Chi-square test. RESULTS: Haemodynamic changes were not statistically
different in all the three groups A, B and C, whereas at the end of surgery VAS
score of Group A subjects was significantly higher (4.93+/-0.98) as compared to
Group B (1.73+/-0.64) and Group C (1.40+/-0.50). On 2(nd) postoperative day, no
pain was reported by the Group C patients and on 4(th) day after surgery, no pain
was reported by Group B patients. CONCLUSION: The transdermal buprenorphine patch
(20mg) was effective in attenuating postoperative pain, maintaining haemodynamic
stability requiring no rescue analgesia, with fewer postoperative rescue
analgesic requirements in low dose of buprenorphine patch (10mg) group.
PMID- 27504384
TI - Supraclavicular Brachial Plexus Block With or Without Dexamethasone as an
Adjuvant to 0.5% Levobupivacaine: A Comparative Study.
AB - INTRODUCTION: Brachial plexus block is an excellent method for attaining optimal
operating conditions by producing complete muscular relaxation, maintaining
stable intraoperative haemodynamics and the associated sympathetic block. In
addition, they provide extended postoperative analgesia with minimal side
effects. Different adjuvants have been described in literature to hasten the
onset and prolong the duration of block. The present study was conducted to study
the effect of adding dexamethasone to levobupivacaine in supraclavicular brachial
plexus block. AIM: To observe the effect of dexamethasone on onset and duration
of anaesthesia, when used as an adjuvant to levobupivacaine in supraclavicular
brachial plexus block. MATERIALS AND METHODS: A total of 60 patients in the age
group of 18-65 years belonging to ASA physical status I or II were included in
the study. They are randomly allocated in two groups and each group included 30
patients. In group 1, patients received 30ml of 0.5% isobaric levobupivacaine
with 2ml of isotonic sodium chloride. In group 2 patients received 8mg (2ml)
dexamethasone in addition to 30ml of 0.5% isobaric levobupivacaine. RESULTS: The
results showed that the onset of sensory and motor block were faster in group
2(p<0.05). The duration of sensory and motor block were significantly longer in
group 2 (p<0.05). VAS score at 12 hours were significantly lower in group 2
(p<0.05). None of the patients had bradycardia, hypotension or any other side
effects. CONCLUSION: Dexamethasone added to levobupivacaine for supraclavicular
brachial plexus block reduces the time to onset of sensory and motor blockage and
prolongs the duration of analgesia.
PMID- 27504385
TI - LBBB with History of Complete Atrioventricular Dissociation Underwent Bipolar
Hemiarthroplasty.
AB - A 70-year-old female patient, known case of hypertension and incomplete Left
bundle branch block (LBBB), posted for bipolar hemiarthroplasty. A geriatric
patient with LBBB and systemic hypertension is a fatal combination; it may
precipitate into complete AV dissociation during anaesthesia and surgical stress.
We are reporting this interesting case as our patient had developed complete
Atrioventricular (AV) dissociation when scheduled earlier for surgery and got
postponed. We had given combined spinal epidural anaesthesia and managed
successfully without any complication.
PMID- 27504386
TI - Anaesthetic Management of Caesarean Section in a Term Pregnancy with Ventricular
Septal Defect and Pulmonary Hypertension with Severe Pulmonary Stenosis.
AB - Pregnancy with pulmonary hypertension - WHO risk class IV cardiac disease is
associated with significant haemodynamic burden due to cardiocirculatory changes
which is a significant indirect cause of maternal mortality. We report a very
rare case - primigravida term pregnancy with pulmonary hypertension, large
ventricular septal defect (2.4 cm(2)), bidirectional shunt mainly left to right
with severe pulmonary stenosis with peak gradient of 144mmHg. Caesarean section
was done under general anaesthesia with successful maternal and neonatal outcome.
PMID- 27504387
TI - Effects of Yoga on Physiological Indices, Anxiety and Social Functioning in
Multiple Sclerosis Patients: A Randomized Trial.
AB - INTRODUCTION: Multiple sclerosis (MS) as a chronic disease could affect patients'
various domains of life. AIM: This study was conducted to study the effect of
yoga on the physiological indices, anxiety and social functioning of patients
with MS in southwest, Iran. MATERIALS AND METHODS: In this clinical trial study,
60 MS patients were enrolled according to inclusion criteria and randomly
assigned to two groups of 30 each. Prior to and after intervention, the patients'
vital signs were measured. For case group yoga exercises were performed three
sessions a week for 12 weeks while control group performed no exercise. The data
were gathered by questionnaire and analysed by descriptive and analytical
statistics in SPSS. RESULTS: Prior to intervention, there was no significant
difference in fatigue severity and pain between the two groups but the mean
fatigue severity and pain in case group decreased compared to the control group
after the intervention. Prior to intervention, there was no significant
difference in mean physiological indices between the two groups but the mean
physiological indices in case group decreased significantly after the
intervention (p<0.05). CONCLUSION: Yoga is likely to increase self-efficacy of MS
patients through enhancing physical activity, increasing the strength of lower
limbs and balance, and decreasing fatigue and pain, and finally to promote social
functioning and to relieve stress and anxiety in these patients.
PMID- 27504388
TI - Rising Trend of Use of Antidepressants Induced Non- Puerperal Lactation: A Case
Report.
AB - Non puerperal lactation or galactorrhea is a well known side effect of
antipsychotic drugs but has been infrequently described with the use of
antidepressants. In past few decades, there have been emerging trend of isolated
case reports of selective serotonin reuptake inhibitors induced non puerperal
lactation. We report a case of non puerperal lactation following usage of second
generation tricyclic antidepressant, nortriptyline and resolution on withdrawing
the drug. Literature review has been done for antidepressant induced galactorrhea
to understand the current trends, putative mechanism as different from one
implicated for antipsychotics and its clinical utility.
PMID- 27504389
TI - Digital Acrometastasis as Initial Presentation in Carcinoma of Lung A Case Report
and Review of Literature.
AB - Bony metastases develop in 30% of all the cancers, but out of which only 1% to 3%
occurs in the hand. Lung is the most common site for acrometastasis, followed by
breast and renal cell cancer. Metastases to the digits are with non-specific
presentation. We reported a case of 79-year-old male patient with initial
presentation of swelling over left index finger, which was found to be squamous
cell carcinoma of finger on histopathological examination. He was subsequently
diagnosed as a case of squamous cell carcinoma of lung with acrometastasis.
PMID- 27504390
TI - Adenolipoma of the Breast: A Clinicoradiological Entity and Pathologist's
Dilemma!
AB - Breast hamartomas are benign lesions composed of variety of normal breast
components arranged in disorganized manner. These are rare and classified as
adenolipoma, fibrolipoma, adenofibrolipoma, etc. Clinically these present as
painless well-circumscribed, mobile lumps of breast. Incidence and etiology
remain obscure due to its rarity. These have been described in women in their
40's or 50's. Mammographically they appear non homogenous mass with circumscribed
fatty masses. Histologically they appear as circumscribed masses with variable
amount of fat, fibrous and glandular tissue. Here we are presenting adenolipoma
in 29-year-old woman with review of literature.
PMID- 27504391
TI - Exploring the Management of Radiation Proctitis in Current Clinical Practice.
AB - INTRODUCTION: Radiation proctitis is radiation induced rectal mucositis,
occurring as a consequence to radiation therapy of the pelvic organs for various
pelvic region malignancies. The management of radiation proctitis is extremely
challenging as no recommended guidelines are available and limited number of
studies are there in the literature involving the various treatment options. AIM:
The aim of the study is the in-depth review of published literature to see the
role of various treatment modalities in the management of radiation proctitis.
MATERIALS AND METHODS: An integrative review was undertaken within PubMed,
MEDLINE, PMC, GOOGLE SEARCH databases and articles published upto February 2015
were reviewed and analysed. A total of 54 studies were included. RESULTS:
Literature suggests that non surgical therapies are the first line of treatment
and surgery is reserved for advanced or refractory cases. Endoscopic therapies
form the mainstay of treatment in managing the patients of radiation proctitis.
Argon plasma coagulation and laser therapies are preferred. Radiofrequency
ablation, cryoablation and mesenchymal stem cell therapy are the upcoming
modalities. Medical therapy can be tried alone or in conjunction to endoscopic
therapies. In the resistant or refractory cases, surgery can be looked for in the
form of diversion or resection with or without anastamosis. CONCLUSION: Though, a
number of options are available, still a lot can be explored in this field to
improve the morbidity in the patients and to confirm the superiority of one
treatment over other.
PMID- 27504392
TI - Primary Hodgkin's Lymphoma of the Sternum: Report of a Case and Review of the
Literature.
AB - Sternal masses present a unique diagnostic challenge in clinical practice. A wide
array of differential diagnosis of a sternal mass includes osteomyelitis,
tuberculosis, eosinophilic granuloma, sarcoma and lymphoma (usually Non
Hodgkin's) amongst others. Sternum is a rare site of Hodgkin's lymphoma and is
usually misdiagnosed as tuberculosis or eosinophilic granuloma on routine
histopathology. This delayed diagnosis culminates in death of patients. We report
a 30-year-old lady who presented with swelling in upper part of chest wall since
1 month. Past history was significant for a similar swelling 2 years back, which
was diagnosed as hodgkin's lymphoma and treated with 4 cycles of chemotherapy at
another centre (which led to resolution of the swelling). Examination revealed a
6x6.5cm firm swelling originating from the upper part of sternum. There was no
lymphadenopathy or organomegaly. Histopathological examination (with
immunohistochemistry) of the trucut biopsy from the swelling confirmed the
diagnosis of Hodgkin's lymphoma (nodular sclerosis). Patient was diagnosed as a
late relapse of primary sternal Hodgkin's lymphoma (stage IBE) and was
administered 4 cycles of ABVD followed by local radiotherapy to the involved site
which led to complete resolution of the disease as assessed by PET scan. We
present this unusual case of primary sternal Hodgkin's lymphoma. Rarity of this
entity, with diagnostic challenges encountered and treatment options available
are highlighted in the current report. A pubmed search revealed 18 cases of
sternal involvement in Hodgkin's lymphoma which have been tabulated.
PMID- 27504393
TI - Multiple Myeloma: An Unusual Cause of Extensive Bone Marrow Necrosis.
PMID- 27504394
TI - Evaluation of Autonomic Dysfunction in Obese and Non-Obese Hypertensive Subjects.
AB - INTRODUCTION: Obesity and more specifically, visceral obesity, has been
consistently associated with hypertension and increased cardiovascular risk.
Epidemiological studies indicate that at least two-third of the prevalence of
hypertension can be directly attributed to obesity. Studies also suggest that
hypertensive patients have impaired cardiac autonomic function. AIM: The
objective of the study was to examine any added effects of obesity on cardiac
autonomic dysfunction in hypertensive patients. MATERIALS AND METHODS:
Hypertensive subjects (n=45) between 35-60 years of age were divided into two
groups; Group A (n=30) consisted of non-obese hypertensive subjects and Group B
(n=15) consisted of obese (BMI>=30kg/m(2)) hypertensive subjects. Cardiac
autonomic function was assessed using four tests - Heart rate response to
immediate standing (30:15 ratio), standing to lying ratio (S/L ratio), Blood
pressure response to immediate standing and Cold Pressor Test (CPT). RESULTS:
There were no significant differences for autonomic function tests between obese
and non-obese hypertensive subjects (p >0.05). CONCLUSION: The results showed
that there are no significant differences in the cardiac autonomic function
responses between obese and non-obese hypertensive subjects.
PMID- 27504395
TI - An Accelerated Multi-Modality Rehabilitation Protocol Combined with Botulinum
Toxin-A Injection in Adult Idiopathic Toe Walking: Case Report.
AB - Diagnosis of Adult Idiopathic Toe Walking (AITW) is very rare in clinical
practice. High quality studies regarding AITW and its treatment options have not
been conducted previously. A 28-year-old male patient complaining of lower leg
pain was referred to outpatient rehabilitation clinic. Physical examination
revealed a gait abnormality of insufficient heel strike at initial contact. The
aetiology was investigated and the patient's walking parameters were assessed
using a computerized gait analysis system. The AITW was diagnosed. Botulinum
toxin-A (Dysport((r))) was injected to the bilateral gastrocnemius muscles. A
combined 10-days rehabilitation program was designed, including a daily one-hour
physiotherapist supervised exercise program, ankle dorsiflexion exercises using
an EMG-biofeedback unit assisted virtual rehabilitation system (Biometrics) and
virtual gait training (Rehawalk) every other day. After treatment, the patient
was able to heel strike at the initiation of the stance phase of the gait. Ankle
dorsiflexion range of motions increased. The most prominent improvement was seen
in maximum pressure and heel force. In addition center of pressure evaluations
were also improved. To the best of our knowledge this is the first case, of AITW
treated with combined botulinum toxin, exercise and virtual rehabilitation
systems. This short report demonstrates the rapid effect of this 10-days combined
therapy.
PMID- 27504396
TI - An Insight into Health Care Setup in National Capital Region of India using
Dimensions of Learning Organizations Questionnaire (DLOQ)- A Cross-Sectional
Study.
AB - INTRODUCTION: Over the past decades India, though being a developing country has
progressed in multiple sectors but has not shown a substantial qualitative
progress in healthcare. To be able to evaluate learning organization in a
healthcare setup would thrust millennium development goals and infuse continuous
learning model into health sector. AIM: To assess health care context using the
Dimensions of the Learning Organization Questionnaire (DLOQ) in a health care
setting in National Capital Region of India. MATERIALS AND METHODS: DLOQ proforma
were distributed among 315 employees at all levels of the hospital. Data was
analysed using SPSS software version 19.0 and was subjected to quantitative
analysis and non-parametric tests. RESULTS: The Kruskal-Wallis test indicated a
significant difference between the means of the different professions where as
Mann-Whitney tests compared the relation between each of the profession and a
significant difference (p < 0.05) was noted, except dimension "systems
connection". CONCLUSION: The results provided sufficient inputs about the
multidimensional learning organization capacity of a health care setting in a
rapidly developing country.
PMID- 27504397
TI - Efficacy of Different Methods for Removing Root Canal Filling Material in
Retreatment - An In-vitro Study.
AB - INTRODUCTION: Although success of endodontic therapy has significantly improved
in the last few decades due to the introduction of novel materials and
techniques, failures of endodontic therapy requiring re-treatment still comprise
a significant percentage of patients requiring root canal treatment. AIM: To
evaluate and compare the effective removal of gutta percha and sealer, amount of
apical debris extrusion and time required for gutta percha removal using various
endodontic files. MATERIALS AND METHODS: Total 48 extracted mandibular premolars
were mounted on acrylic blocks and endodontic procedure was carried out using
size 40 K file and obturated using guttapercha and zinc oxide eugenol sealer.
After one month storage, samples were decoronated, mounted on screw capped vials
and subjected to removal of obturated material by four instruments: H files, safe
sided H files, protaper universal retreatment rotary system and ultrasonic
retreatment tip, grouped as 1, 2, 3, and 4 respectively. Only 2mm of obturated
material from the coronal part was removed using no. 3 Gates Glidden drill,
guttapercha was softened with a drop of xylene for 2 mins for each canal and
retreatment was performed. The retreatment procedure was said to be complete when
no visible debris were observed on the instrument flutes. The samples split into
two halves and examined under stereomicroscope, photographed, assessed using
AUTOCAD software and percentage of remaining filling material in coronal, middle,
apical thirds of the canal was calculated in mm(2). Retreatment time was recorded
in seconds and apically extruded debris was assessed by microbalance in grams for
each tooth. The data was analyzed by using descriptive statistics, ANOVA and
Scheffe's post hoc test through SPSS for windows (v 16.0). RESULTS: The
ultrasonic retreatment tip had less percentage of residual guttapercha/sealer,
shorter mean operating time and little apical extrusion with a significant
difference (p<0.05) between the other groups. CONCLUSION: All techniques retained
guttapercha/sealer remnants within the root canal. The ultrasonic retreatment tip
proved to be an efficient method of removing obturated material. It was fastest
with least apical debris extrusion.
PMID- 27504398
TI - Comparative Evaluation of Preemptive Analgesic Effect of Injected Intramuscular
Diclofenac and Ketorolac after Third Molar Surgery- A Randomized Controlled
Trial.
AB - INTRODUCTION: Analgesia pre-emptively administered effect-ively aid in management
of pain. Pre-emptive analgesia is anti-nociceptive treatment which prevents
altered central sensitization of afferent inputs. AIM: To compare and evaluate
the pre-emptive analgesic efficacy of preoperatively administered ketorolac and
diclofenac for controlling postoperative pain after third molar surgery.
MATERIALS AND METHODS: A total of 50 patients with symmetrically impacted third
molars were divided into two groups, 30mg intramuscular injection of ketorolac
and 75 mg diclofenac sodium were used in the respective groups. The visual
analogue scale was used to assess post operative pain for three days and the
patients were also evaluated for the number of rescue analgesia. RESULTS: The
data was statistically evaluated with paired t- test. The maximum time taken for
pain perception for Group A Ketoralac was 5.48 hrs and Group B Diclofenac sodium
was 4.9 hrs and p=0.235 which was not significant. The mean number of tablets
taken by the patients in the first three post operative days was 3.24 in Group A
i.e., Ketorolac and 4.04 in Group B i.e., Diclofenac sodium. The values were
compared using the paired t test. The p value = 0.004, which was significant.
CONCLUSION: Ketoralac showed better pre-emptive analgesic effect for post
operative pain management after third molar extraction. The immediate post
operative pain free period provided by both ketorolac and diclofenac by
intramuscular route was same.
PMID- 27504399
TI - Evaluation of a New Self-Reported Tool for Periodontitis Screening.
AB - INTRODUCTION: Periodontitis is still highly prevalent in industrial population
whereas at the same time appropriate screening programs are missing. AIM: To
evaluate, a self-reported questionnaire about periodontal risk factors in
combination with the Periodontal Screening Index (PSI) to identify an existing
need for periodontal treatment combined with the early recognition of high-risk
patients. MATERIALS AND METHODS: Total 200 patients took part in the
questionnaire based study and were examined using the PSI. Thereafter the
participants were divided into two groups, subjects with periodontitis (Group 1;
PSI 0-2) and subjects without periodontitis (Group 2; PSI 3-4). The answers were
evaluated using a point system ranging from 0 to 8, based on known periodontal
risk factors and their assumed degree of influence. Receiver-Operating
Characteristic (ROC) curve analysis were applied to examine the overall
discriminatory power, sensitivity, specificity and corresponding cut-off points
of the self-reported periodontal disease scale. RESULTS: There was a significant
difference between Group 1 and 2 concerning the majority of the inquired items
(12 of 16, p<0.05). The distribution of the individual total score exhibited a
high statistical significance (p<0.001) of robustness in terms of differing
definitions of periodontitis. The Area Under the Curve (AUC) was 0.912 with a
sensitivity of 86% and a specificity of 76%. CONCLUSION: The questionnaire
produced a reliable assessment of the individual risk (total score) and the need
for periodontal treatment as well as the differentiation between gingivitis and
periodontitis. CLINICAL RELEVANCE: Patient-based data (clinical variables and
periodontal risk factors of periodontitis) were adequate to make a preliminary
assessment of a possible need for periodontal treatment.
PMID- 27504400
TI - Evaluation of Antibacterial Efficacy of MTA with and without Additives Like
Silver Zeolite and Chlorhexidine.
AB - INTRODUCTION: Microorganisms, predominantly Enterococcus faecalis are found
responsible in the progression of pulpal, periradicular diseases and in
endodontic failures. Unsuccessful conventional treatment might necessitate the
need for a surgical approach; where in retrograde restorative materials are used
to seal the apex. Among the root end filling materials, Mineral Trioxide
Aggregate (MTA) is considered biocompatible and is most commonly used in clinical
applications but it has limited antibacterial activity. Metallic silver and
chlorhexidine have been added into various dental materials to enhance the
antibacterial activity. AIM: This study aimed to compare the antibacterial effect
of MTA, MTA mixed with silver zeolite and MTA mixed with chlorhexidine against
Enterococcus faecalis. MATERIALS AND METHODS: Test materials used in the study
were divided into three groups namely Group 1- MTA, Group 2-MTA + Silver Zeolite,
Group 3-MTA + Chlorhexidine. Direct contact test was done by placing a
standardized suspension of Enterococcus faecalis on the test materials in a 96
well microtiter plate. The bacterial growth was measured spectrophotometrically
using ELISA reader at intervals of one, three and seven days. STATISTICAL
ANALYSIS: Data was collected by recording the optical density and analyzed using
two-way ANOVA and Tukey's multiple post hoc test followed by paired-t test.
RESULTS AND CONCLUSION: All test groups showed antibacterial activity against
Enterococcus faecalis at day one, three and seven. MTA with silver zeolite showed
the maximum antibacterial activity followed by MTA with 2% chlorhexidine. The
least antibacterial effect was shown by MTA mixed with sterile water.
PMID- 27504401
TI - Clinical Evaluation of Proclination of Lower Anterior Teeth during Alignment
using a Single Width Bracket-A Pilot Study.
AB - INTRODUCTION: The pre-adjusted brackets are available in various prescriptions
and sizes; nevertheless there are still many controversies as to which pre
adjusted edgewise bracket offers the maximum clinical efficiency. AIM: This study
was conducted to determine and compare the amount of lower incisor proclination
during de-crowding if any of the Mini-Uni Twin Brackets with that of the standard
double width brackets. MATERIALS AND METHODS: A total of 20 patients i.e., 10
patients in each group both males and females were randomly selected for the
study from subjects seeking treatment, the selected samples were grouped as
follows. Group I - Double Width Brackets (3M Unitek Gemini Series) 0.018" slot
with Roth prescription. Group II - Mini Uni-Twin Bracket (3M Unitek) 0.018" slot
with Roth prescription. RESULTS: The Mini-Uni Twin Brackets had statistically
significant (p = 0.01) amount of proclination of the lower anteriors (0.8(o)+/-
0.3(o)) after de-crowding as compared to the standard Double Width Brackets and
since the mean change in the Incisor Mandibular Plane Angle (IMPA) was lesser
than 1(o), its clinical significance could be questionable. CONCLUSION: The Mini
Uni Twin brackets are comparatively efficient in the lower anterior decrowding
but further comparative clinical studies need to be performed on these Mini Uni
Twin brackets, with an increase in the sample size and also the number of
parameters to prove its total clinical efficiency.
PMID- 27504402
TI - Minocycline Ointment as a Local Drug Delivery in the Treatment of Generalized
Chronic Periodontitis - A Clinical Study.
AB - INTRODUCTION: The primary goal in periodontal therapy includes removal of the
etiological factors by mechanical periodontal treatment, which sometimes fail to
eliminate the anaerobic infection at the base of the pocket and requires adjuvant
chemical therapy. AIM: The aim of the study was to evaluate the effectiveness of
2% minocycline ointment when used as an adjunct to periodontal flap surgery and
post-operative maintenance period for the treatment of generalized chronic
periodontitis. MATERIALS AND METHODS: The study included 30 subjects comprising
of 60 posterior sextants in a split mouth design in which 30 sextants were
treated as experimental and 30 sextants as control with a probing pocket
depth>=6mm. In Group A (experimental group) 30 sextants were treated with open
flap debridement followed by the application of minocycline ointment as a local
drug delivery. In Group B (control group) 30 sextants were treated with open flap
debridement alone. Minocycline hydrochloride ointment was applied on the 0 day
and 3(rd) month. The clinical parameters such as plaque index, probing pocket
depth, clinical attachment level and gingival bleeding index were recorded at 0
day, 3(rd) month and 6(th) month in both the groups. Paired and unpaired t-test
were used to compare the means of the two groups. RESULTS: When Group A and Group
B were compared, Group A showed significantly greater reduction in gingival
bleeding index, probing pocket depth and gain in clinical attachment level than
Group B, from 0 day to 3 months and from 0 day to 6 months. Group A showed
significant reduction in plaque index than Group B when they were compared at 6
months. CONCLUSION: The results demonstrate that there was significant reduction
in the clinical parameters with improvement in the periodontal status on
application of minocycline ointment as an adjunct to periodontal flap surgery in
generalized chronic periodontitis.
PMID- 27504403
TI - Comparison of K-loop Molar Distalization with that of Pendulum Appliance - A
Prospective Comparative Study.
AB - INTRODUCTION: Molar distalization is the non extraction method of managing Class
II malocclusions. AIM: The purpose of this study was to evaluate the skeletal and
dentoalveolar effects of maxillary molar distalization with K-loop appliance, and
to compare these effects with that of pendulum group. MATERIALS AND METHODS:
Class I and dental Class II malocclusions were divided into two groups of 15
each: In Group 1 (nine females and six males; mean age, 16.0+/-2.6 years)
patients were treated with K-Loop molar distalization supported palatally by
Nance button, while in Group 2 (seven females and eight males; mean age, 15.4+/
4.7 years), the patients were treated with conventional pendulum appliance.
Standardized lateral cephalograms were taken at the beginning of treatment (T0)
and at the end of molar distalization (T1) and the changes were statistically
analyzed with paired t-test. RESULTS: The results showed no statistically
significant difference in the amount of molar distalization in either of the
appliance groups: the mean amount of molar distal movement of 5.1+/-0.8 mm and
4.93+/-1.68 mm was observed in the Group 1 and 2 respectively. The incisors moved
mesially by 1.3+/-0.63 mm in Group 1 and 1.57+/-0.58 mm in Group 2. CONCLUSION: K
Loop molar distalizing appliance has similar skeletal and dentoalveolar effects
as that of pendulum appliance, with the advantages of simple yet efficient to
control the moment-force ratio to produce all types of tooth movements and also
requires minimal patient co-operation.
PMID- 27504404
TI - Assessment of Factors Affecting Adolescent Patients' Compliance with Hawley and
Vacuum Formed Retainers.
AB - INTRODUCTION: Success of orthodontic retention with removable retainers almost
entirely depends on patients' compliance. AIM: This study was carried out to
investigate the relationship between adolescent orthodontic patients' compliance
and various clinical and social factors. MATERIALS AND METHODS: The data were
collected from 77 orthodontic patients aged 7-11 years old who had finished the
full fixed appliance therapy. Hawley's retainers were used in 34 patients and 43
patients used Vacuum Formed Retainers (VFRs). The subjects completed a
questionnaire including several identifiers allowing the respondents to be
classified into subgroups. They were also asked to indicate how long they wore
their retainers during the day, by writing the number of hours in the report-card
for the next three months. Comparison of the results was performed by one-way
ANOVA and independent sample-t tests. RESULTS: No significant differences were
found between males and females. Type of the retainer, patients' grade of study,
mothers' occupation, clinicians' and parents' attitudes and filling the report
cards had significant effect on mean wear hours per day. When compliance of the
patients was assessed according to treatment location, Living place, parents'
educational degrees and ethnicity, no significant differences could be found.
CONCLUSION: The adolescent patients' compliance was greater with VFRs than with
Hawley's retainers. Parental attitude and doctor-patient relationship had a great
impact on adolescent patients' compliance.
PMID- 27504405
TI - Expression of CD1a by Langerhan's Cells in Oral Lichen Planus - A Retrospective
Analysis.
AB - INTRODUCTION: Langerhan's Cells (LCs) are dendritic cells of the oral epithelium
which play a role in a series of oral lesions from gingivitis to oral cancer.
Oral Lichen Planus (OLP) is an oral mucosal T-lymphocyte mediated immunologic
reaction to an unidentified putative antigen or allergen. AIM: The aim of this
study was to quantify the presence of immature LCs in OLP comparing them with
normal epithelium. MATERIALS AND METHODS: A retrospective study using 30 of OLP
cases were conducted. Immunohistochemistry was performed using polyclonal anti
CD1a antibodies to identify LCs in 10 cases of normal tissue and 30 samples of
OLP. The distribution of LCs among lesional tissue and normal mucosa was analysed
using Mann-Whitney U test. RESULTS: LC population in OLP was significantly higher
when compared to the normal epithelium (p<0.001). CONCLUSION: The increase in LCs
indicates the active role played during the antigen detection in OLP and
subsequent presentation to T-lymphocytes.
PMID- 27504406
TI - Detection of Porphyromonas gingivalis fimA Type I Genotype in Gingivitis by Real
Time PCR-A Pilot Study.
AB - INTRODUCTION: Published literature till date reveals a high prevalence of
Porphyromonas gingivalis fimA type I genotype among healthy subjects. Quite a few
studies have reported its prevalence also in periodontitis patients. Nevertheless
incidence of this genotype in gingivitis is lacking in adult population. AIM: The
present study was chosen to detect P. gingivalis fimA type I genotype among
chronic gingivitis patients. MATERIALS AND METHODS: A total of 46 subgingival
plaque samples collected from chronic marginal gingivitis (n=23) and chronic
periodontitis subjects (control group) (n=23) were subjected to Real-Time
Polymerase Chain Reaction to detect the P. gingivalis fimA type I gene.
Statistical analysis was performed using chi-square test. RESULTS: Prevalence of
P. gingivalis fimA type I gene among chronic periodontitis and chronic gingivitis
patients were 8.7% and 30.4% respectively. P. gingivalis fimA type I genotype
prevalence was found to be statistically insignificant between the two study
groups (p=0.135). CONCLUSION: The avirulent P. gingivalis fimA type I genotype,
occurred in high prevalence among chronic gingivitis patients, while its presence
was low in chronic periodontitis patients. Presence of this avirulent genotype in
chronic marginal gingivitis signifies its reversible condition.
PMID- 27504407
TI - Effects of Preheated Composite on Micro leakage-An in-vitro Study.
AB - INTRODUCTION: Resin composites have been the pinnacle of direct esthetic
restorations ever since its discovery. However, it comes with its own
disadvantages. Post-operative sensitivity and marginal discoloration frequently
occur due to polymerization shrinkage and micro leakage, which is the major cause
of failure in resin composite restorations. AIM: To evaluate the effects of
preheated composite at different temperatures on microleakage. MATERIALS AND
METHODS: A total of 60 extracted non-carious human premolars were collected and
class 1 cavity (1.5x4x 3mm) was prepared in each and were randomly divided into
three groups. Group 1 (n=20) was filled with microhybrid resin composite (Heraeus
Charisma Smile) at room temperature. Group 2 (n=20) was filled with the same
resin composite which was preheated to 50 degrees C and Group 3 (n=20) was filled
with resin composite preheated to 60 degrees C. Teeth were subjected to a
thermocycling regime (500X, 5 - 55 degrees C), followed by a dye infiltration by
immersing in basic fuschin for 24 hours. The tooth was sectioned longitudinally
and the extent or absence of micro-leakage was determined by the amount of dye
penetration along the resin composite-tooth interface using a confocal
microscope. RESULTS: There was minor micro-leakage detected at the occlusal
margin of the control tooth specimen. The sample with preheated composite
restoration at 50 degrees C showed an intact tooth-restoration interface with no
micro leakage. However, the preheated composite at 60 degrees C showed large
amount of microleakage. CONCLUSION: Under the current limitation of the study,
preheated composite at 50 degrees C showed the least micro-leakage.
PMID- 27504409
TI - Effect of Calcium Hydroxide, Chlorhexidine Digluconate and Camphorated
Monochlorophenol on the Sealing Ability of Biodentine Apical Plug.
AB - INTRODUCTION: Teeth with immature apex are managed by establishing an apical plug
using various materials and techniques. However, the use of previously placed
intracanal medicament may affect the sealing ability of permanent filling
material used as an apical plug. AIM: To evaluate the effect of removal of
previously placed Calcium Hydroxide, Chlorhexidine Digluconate and Camphorated
Monochlorophenol as an intracanal medicament on the sealing ability of the
Biodentine as an apical plug. MATERIALS AND METHODS: A total of 72 recently
extracted human permanent teeth with single root were selected and stored in
saline at room temperature. The crown portion of each tooth was removed at the
level of cemento enamel junction; 14mm root length was taken as standard length.
All the roots were submerged in 20% sulphuric acid up to 3 mm from the apex, for
four days for root resorption. One sample was cut longitudinally to look for root
resorption under stereo microscope. The canal preparation was done; the roots
were kept in moist gauze after instrumentation. A total of 71 roots were randomly
divided into three groups. GROUP 1:Calcium hydroxide paste, GROUP 2:
Chlorhexidine digluconate, GROUP 3: Camphorated Monochlorophenol (CMCP). The
medicaments were removed with stainless steel hand files and 0.5% sodium
hypochlorite irrigation. After removal of medicament Biodentine was placed in
apical third of resorbed roots and the remaining portion of the canals was filled
with gutta-percha. All the 71 roots were analysed with fluid filtration method
for evaluating microleakage. RESULTS: Comparing all the three groups
statistically there was no significant difference. The mean values were found
more for group 1 followed by group 2 & 3. CONCLUSION: All the groups showed
microleakage. Calcium hydroxide showed the maximum microleakage followed by
Chlorhexidine digluconate and least with CMCP.
PMID- 27504408
TI - An in vitro Comparative Evaluation of Three Remineralizing Agents using Confocal
Microscopy.
AB - INTRODUCTION: The caries process has been thought to be irreversible, resulting
in the permanent loss of tooth substance and eventually the development of a
cavity. Recent approaches focused on application of remineralizing agents to
incipient carious lesions, aim at controlling demineralization and promoting
remineralization. Remineralizing agents create a supersaturated environment
around the lesion; thus, preventing mineral loss and forces calcium and phosphate
ions in the vacant areas. AIM: To compare and evaluate the remineralization
potential of Fluoride Varnish, CPP-ACP Paste (Casein Phosphopeptide-Amorphous
Calcium Phosphate) and fTCP Paste (functionalized Tricalcium Phosphate) using
confocal microscope. MATERIALS AND METHODS: Two windows of 3X3mm were created on
the labial cervical and incisal thirds in 60 permanent maxillary central
incisors. The teeth were demineralized to create artificial caries and divided
into three groups of 20 each. Group I specimens were coated with Fluoride Varnish
once whereas those in CPP-ACP paste group and fTCP group were brushed for 2
minutes, twice daily for 20 and 40 days. The specimens were stored in artificial
saliva during the study period and were later sectioned and observed under
confocal microscope. Data obtained was statistically analyzed using Fischer's
exact test, ANOVA and post-hoc Bonferroni's test. RESULTS: Fluoride Varnish, CPP
ACP Paste and fTCP Paste showed remineralization of artificial carious lesions at
both the time intervals. Fluoride varnish showed the highest remineralization
followed by CPP-ACP Paste and fTCP Paste. A statistically significant increase in
remineralization potential of CPP-ACP Paste and fTCP Paste was observed at the
end of 40 days as compared to 20 days. CONCLUSION: Fluoride varnish showed the
greatest remineralization potential of artificial carious lesions followed by CPP
ACP Paste and fTCP Paste respectively.
PMID- 27504410
TI - Comparative Evaluation of Ciprofloxacin Levels in GCF and Plasma of Chronic
Periodontitis Patients: Quasi Experimental Study.
AB - INTRODUCTION: For any antimicrobial approach to be successful in periodontal
therapy, it is important that the antimicrobial agent targets the sub-gingival
biofilm by attaining sufficient concentration at the sub-gingival site. AIM: The
purpose of the present study was to determine and compare the concentrations of
ciprofloxacin present in Gingival Crevicular Fluid (GCF) and plasma after its
systemic administration. MATERIALS AND METHODS: A total of 20 subjects, in the
age group of 30-60 years satisfying the inclusion and exclusion criteria, were
chosen from the outpatient Department of Periodontology, Government Dental
College and Hospital, Hyderabad and consent was obtained. Subjects were put on
oral ciprofloxacin therapy (Baycip, Bayer Corporation) of 500mg twice daily doses
for five days to establish steady state tissue levels of the agent. GCF and serum
samples were collected at the 72(nd) hour after the first dose of ciprofloxacin
and were compared using unpaired t test. RESULTS: The mean gingival index value
of the subjects was 1.8 +/- 0.59 and the mean probing depth of the subjects taken
in the study was 5.724 +/- 0.47mm. The results of this study showed that
ciprofloxacin concentrations were significantly higher (p<0.001) in GCF than in
plasma. CONCLUSION: Results from the present study and those from the earlier
studies clearly indicate the ciprofloxacin's ability to reach and concentrate in
infected periodontal sites via GCF. This property of ciprofloxacin may be useful
for eradication of periodontal pathogens, thus improving the outcome of
periodontal therapy.
PMID- 27504411
TI - Assessment of Skeletal Maturation in Concordance to Statural Height and Body
Weight in 12-Year-Old Children - A Cross-Sectional Study.
AB - INTRODUCTION: To analyse the importance of bodily characteristics of growing
children and its correlation towards skeletal maturity. This further aids
orthodontists in proper treatment planning. AIM: The purpose of this study was to
assess the correlation between cervical vertebrae maturation, statural height and
body weight as measured in 12 -year-old children. MATERIALS AND METHODS: Lateral
cephalograms were taken as a part of treatment records in 94 children along with
their statural height and body weight. The Cervical Vertebrae Maturation Index
(CVMI) was used to trace the C2, C3 and C4 vertebrae respectively and the data
were then correlated to the chart provided by the Indian Council for Medical
Research (ICMR). RESULTS: The overall sample showed a statistically significant
correlation between CVMI and height (p=0.047). Girls showed significant
correlation in their mean heights to the CVMI staging (p=0.012) while the boys
exhibited a maximal mean height value in Cervical Stage (CS) 5 followed by CS3.
There was no significant correlation between weight and CVMI. The mean CVMI stage
seen in boys and girls were CS2 and CS3 respectively. CONCLUSION: There exists a
definitive correlation between height and CVMI stages in growing children. Girls
showed an advanced level of skeletal maturity in comparison to boys. CVMI staging
should be used along with statural height and body weight when considering growth
modification procedures.
PMID- 27504412
TI - Estimation of Salivary and Serum Biomarkers in Diabetic and Non Diabetic Patients
- A Comparative Study.
AB - INTRODUCTION: Blood is the gold standard body fluid for diagnosis of Diabetes
Mellitus (DM) but saliva offers an alternative to serum as a biological fluid for
diagnostic purposes because it contains serum constituents. AIM: The study was
conducted to estimate and compare serum and salivary glucose, amylase, proteins,
calcium and phosphorus levels in DM and healthy subjects and to evaluate whether
saliva can be used as a diagnostic fluid in DM patients. MATERIALS AND METHODS:
Study consisted of 120 subjects from OPD of Surendera Dental College,
Sriganganagar, Rajasthan, India. The study groups were divided into Group I-60 DM
patients (Type I & II) and Group II-60 healthy subjects. The saliva and serum
samples were collected from each subject and levels of different biochemical
parameters were estimated. RESULTS: Mean serum level of glucose (211.50 +/-
43.82), amylase (79.86 +/- 16.23), total proteins (6.65 +/- 0.84), calcium (7.17
+/- 0.91) and phosphorus (3.68+/-0.65) as observed in Group I while in Group II,
glucose (88.81+/-11.29), amylase (77.67+/-14.88), total proteins (6.35+/-0.76),
calcium (7.52+/-0.97) and phosphorus (3.96 +/- 0.91) were noted. Mean salivary
level of glucose (14.10+/-6.99), amylase (1671.42+/-569.86), total proteins
(1.33+/-1.11), calcium (10.06+/-2.76) and phosphorus (13.75+/-4.45) as observed
in Group I while in Group II, glucose (5.87+/- 2.42), amylase (1397.59 +/
415.97), total proteins (1.36+/-0.81), calcium (7.73+/-2.78) and phosphorus (8.39
+/- 1.95) were noted. On comparing values in saliva and serum, among two groups,
an insignificant difference (p>0.005) was found between few of them. CONCLUSION:
Values regarding blood and salivary biochemical parameters were distinctly
different between two groups suggesting salivary parameters can be used as a
diagnostic alternative to blood parameters for diabetes mellitus.
PMID- 27504413
TI - Buccal Micronucleus Cytome Assay in Sickle Cell Disease.
AB - INTRODUCTION: Sickle Cell Anaemia (SCA) is a commonly inherited blood disorder
preceded by episodes of pain, chronic haemolytic anaemia and severe infections.
The underlying phenomenon which causes this disease is the point mutation in the
haemoglobin beta gene (Hbbeta) found on chromosome 11 p. Increased oxidative
stress leads to DNA damage. DNA damage occurring in such conditions can be
studied by the buccal micronucleus cytome assay, which is a minimally invasive
method for studying chromosomal instability, cell death and regenerative
potential of human buccal tissue. AIM: To evaluate genomic instability in
patients with sickle cell disease by buccal micronucleus cytome assay. MATERIALS
AND METHODS: The study included 40 sickle cell anemia patients (Group A) and 40
age and sex matched controls (Group B). Buccal swabs were collected and stained
with Papanicolaou (PAP). Number of cells with micronucleus, binuclei, nuclear
bud, pyknosis and karyolysis were counted in two groups as parameters for the
evaluation of genome stability. RESULTS: All the analysis was done using t-test.
A p-value of <0.001 was considered statistically significant. There was a
statistically significant increase in micronuclei number in SCA patients when
compared with controls. Karyolytic (un-nucleated) cell number in Group A was more
than to those of the controls. CONCLUSION: The results might suggest that
patients with sickle cell anaemia have genome instability which is represented by
the presence of micronuclei in the somatic cells. Presence of apoptotic cells
might only indicate the bodily damage to the tissue as a result of the disease.
PMID- 27504414
TI - Assessment of Oral Health Knowledge, Attitude and Self-Care Practice Among
Adolescents - A State Wide Cross- Sectional Study in Manipur, North Eastern
India.
AB - INTRODUCTION: The World Health Organization global strategy of promoting oral
health have shown vast improvements in developed countries but the scenario is
glum among underprivileged communities due to lacunae in implementation of these
promotional programs. Manipur, a North Eastern state in India, is one such
marginalized area. AIM: The study aimed to evaluate Knowledge, Attitude and
Practice (KAP) towards oral health in 15-18 year adolescents residing in Manipur
together with the association of these variables to sociodemographic factors.
MATERIALS AND METHODS: This cross-sectional study included 810 healthy
adolescents drawn from various primary health care centers spanning in all the
nine districts of Manipur. A closed ended questionnaire for the purpose of
collecting data was used in the survey. RESULTS: Of the total participants 90.9%
had high knowledge, 79.8% had favorable attitude and 70.4% had adequate practice
towards oral health. Education of the parents and respondents was the only factor
significantly associated with all three variables, knowledge, attitude and
practice. Significant and positive linear correlation between knowledge-attitude
(r=0.369, p<0.01) knowledge-practice (r=0.405, p<0.01) and attitude-practice (r
=0.353, p<0.01), were observed. CONCLUSION: An overwhelming majority of the
respondents had high knowledge, favorable attitude and sound practice with
respect to oral health. A positive linear correlation exists between the
knowledge, attitude and practice. Evidence based reinforcement programs should be
introduced to further reduce the gap between knowledge, attitude and practice.
The study will also serve as a reference value for use in future evaluation to
help measure the effectiveness of the planned activities. Future research needs
to focus on establishing the dental caries prevalence and oral hygiene status of
Manipuri youth.
PMID- 27504415
TI - Comparison of the Antimicrobial Efficacy of Octenidine Dihydrochloride and
Chlorhexidine with and Without Passive Ultrasonic Irrigation - An Invitro Study.
AB - INTRODUCTION: Elimination of microorganisms from infected root canals is a
complicated task. Numerous measures have been described to reduce the microbial
load in the root canal system, including the use of various instrumentation
techniques, irrigation regimens and intracanal medicaments. The drawbacks of few
commonly used irrigants include toxic and harmful side effects, microbial
resistance to antimicrobial agents and staining. Hence there is a need for
alternative agents which are nontoxic, effective and safe. AIM: To compare and
evaluate antimicrobial effects of 2% Chlorhexidine (CHX) versus 0.1% Octenidine
Dihydrochloride (OCT) as root canal irrigant with and without passive ultrasonic
irrigation against Enterococcus faecalis (E. faecalis) in vitro and to evaluate
the depth of penetration of irrigant solution into the dentinal tubules at the
junction of middle and apical third. MATERIALS AND METHODS: Forty eight freshly
extracted, single rooted human mandibular premolars were decoronated and root
specimen standardized to 14mm. Biofilm of E. faecalis (strain ATCC 29212) was
grown for seven days and the specimens were divided into four groups (n=12) based
on irrigation protocol : Group I- Conventional Syringe Irrigation (CSI) with 2%
CHX, Group II- CSI + 0.1% OCT, Group III-Passive Ultrasonic Irrigation (PUI) + 2%
CHX and Group IV- PUI+ 0.1% OCT. Dentin shavings were collected at two depths
(200MUm and 400MUm) and total number of colony forming units were determined. The
data were statistically analyzed using ANOVA, Scheffes multiple comparison of
means and paired t-test (p<0.05). RESULTS: Group III and IV (PUI) showed
significant difference compared to Group I and II (CSI) both at 200MUm and 400MUm
(p=0.000). For Group III and Group IV no significant differences were found at
200MUm and 400MUm (p=1.000 and 0.363 respectively), however significant
difference was found between data at 200MUm and 400MUm for all the four groups
(p=0.000). CONCLUSION: Octenidine (0.1%) was more effective than 2% Chlorhexidine
against E. faecalis both at 200MUm and 400MUm. Passive ultrasonic irrigation
proved to enhance the antimicrobial action of the irrigants.
PMID- 27504417
TI - Evaluation of Effect of Brushite-Calcite and Two Indigenous Herbs in Removal of
Fluoride from Water.
AB - INTRODUCTION: The acceptable concentration of fluoride in drinking water is
1.5mg/l. Excess fluoride in drinking water causes fluorosis. Fluorosis is an
important public health problem in India. Several treatment technologies
suggested in the past for removing excess fluoride generated and causes various
chemical byproductswhich are hazardous to public. In recent years, there has been
a resurgence of interest to use natural materials due to cost and associated
health and environmental concerns of synthetic organic polymers and inorganic
chemicals. AIM: The aim of this study was to evaluate and compare the
defluoridating capability of the brushite-calcite with that of two indigenous
herbs, tulsi and wheat grass. MATERIALS AND METHODS: One gram of brushite-calcite
combination, tulsi and wheat grass were separately added to 10 containers, each
containing 1.0 l of prepared distilled water with a fluoride concentration of
5ppm and naturally fluoridated water at 2ppm. Half of the samples were boiled for
one minute in a domestic electric kettle for one minute and allowed to cool. The
remaining half of the samples was left un-boiled. Fluoride concentration in all
the samples was assessed at the end of 30 minutes and 24 hours using fluoride ion
selective electrode method. Data was analyzed using unpaired t-test and one-way
ANOVA. RESULTS: For water with 2ppm and 5ppm fluoride, brushite-calcite had shown
highest de-fluoridation capacity (p=0.001) at the end of both 30 minutes and 24
hours in boiled samples whereas tulsi (p=0.001) was most effective in un-boiled
samples. CONCLUSION: The results of the study suggest that tulsi can be used for
domestic water defluoridation as it is economic, safe and effective.
PMID- 27504416
TI - Comparison of Dental Caries Experience in Children Suffering From Epilepsy with
and without Administration of Long Term Liquid Oral Medication.
AB - INTRODUCTION: Sucrose is added as sweetening agent in liquid oral medication
(LOM) to mask the acrid taste of medicines which may be potentially cariogenic.
Many children under long term LOM therapy for treatment of epilepsy may be
susceptible to dental caries. AIM: To assess and compare dental caries experience
in children under long term liquid oral medication with those not under such
medication among 2-12 years old children suffering from epilepsy. MATERIALS AND
METHODS: A cross-sectional study was undertaken on a total of 84 children aged 2
12 years, who were suffering from epilepsy receiving liquid oral medication for
more than 3 months were selected (study group) and for comparison 106 children of
similar age group and disease but on other forms of medication were included as
control group. Dental caries was assessed using DMFT/DMFS (Decayed, Missing,
Fillled Teeth / Surfaces), dmft/dft and dmfs/dfs indices. One-way ANOVA and t
test were used with p-value fixed at 0.05. Univariate logistic regression was
applied. RESULTS: Children on LOM were at increased risk of dental caries than
those with other forms of medications (OR: 2.55, 95% CI (2.37-4.15) p=0.000, HS).
Caries prevalence was high in the study group (76.1%) when compared to control
group (55.6%). CONCLUSION: Long term use of liquid medicines containing sucrose
is a risk factor for dental caries among children with epilepsy.
PMID- 27504418
TI - Evaluation of TLR2 and 4 in Chronic Periodontitis.
AB - INTRODUCTION: Periodontal disease is the major cause of adult tooth loss and is
commonly characterized by a chronic inflammation caused by infection due to oral
bacteria. Members of Toll-Like Receptor (TLR) family recognize conserved
microbial structures, such as bacterial lipopolysaccharides and activate
signalling pathways that result in immune responses against microbial infections.
AIM: The aim of the present study was to assess the mRNA expression of Toll-Like
Receptor 2 and 4 in tissues with or without chronic periodontitis. MATERIALS AND
METHODS: Gingival tissue samples were collected from controls (30 subjects with
healthy periodontal tissues) and experimental group (30 subjects with chronic
periodontitis). Total RNA was extracted and RT-PCR was done for evaluation of TLR
2 and TLR-4. Mann Whitney U-test, Pearson Chi-square Test was used for
statistics. RESULTS: The results showed that there is a significant (p-value=
0.004) association between TLR-4 and the experimental group comprising of chronic
periodontitis patients in comparison to the insignificant (p-value= 0.085) TLR-2
expression. CONCLUSION: This study concludes that TLR-2 and TLR-4 expressed in
the gingival tissues recognize different bacterial cell wall components thus
helping us to associate its potential in diagnosing periodontal disease. Hence,
in the future, these scientific findings can pave the way in using TLR as a
diagnostic biomarker for periodontal disease.
PMID- 27504419
TI - Evaluation of Antifungal Efficacy of Ethanolic Crude Lawsone and Listerine
Mouthwash in Uncontrolled Diabetics and Denture Wearers - A Randomized Clinical
Trial.
AB - INTRODUCTION: Lawsonia Inermis (LI) is a shrub cultivated throughout India. Many
in vitro studies have been done on antifungal activity of LI, although none of
the studies have been conducted invivo. AIM: To evaluate the antifungal efficacy
of ethanolic extract of crude lawsone in comparison with listerine mouth wash in
known diabetics and wearing dentures. MATERIALS AND METHODS: A total of 60
subjects were taken and randomly divided into two groups of 30 each. Group 1
received crude lawsone mouthwash and Group 2 received listerine mouth wash. Oral
rinse technique was performed. Each subject was given distilled water at baseline
and Colony Forming Units (CFU) of candidal species was determined. Post
therapeutic samples were then collected 1hr and 1week following drug usage and
they were further advised to use given mouth washes twice daily with volume of
5ml/rinse for 30 seconds and CFU was evaluated. RESULTS: Crude lawsone mouthwash
showed superior antifungal activity when compared to listerine mouthwash. On
individual comparison of both mouth washes at baseline, 1hr and 1week highly
significant results were obtained using inferential statistics. The inter group
comparison was done using independent t-test where lawsone was considered to be
more effective in reducing CFU, at 1hr and 1week of using the mouth wash
(p<0.01). Subjective symptoms like taste and smell were determined by chi square
test where good taste was felt for lawsone and olfactory satisfaction was good
with listerine (p<0.01). Burning sensation was found to be more with listerine
mouth wash. CONCLUSION: The present study revealed superior antifungal activity
with ethanolic extract of crude lawsone mouth wash compared with listerine
mouthwash.
PMID- 27504420
TI - An Evaluation of the Stress Distribution in Screw Retained Implants of Different
Crown Implant Ratios in Different Bone Densities Under Various Loads-A FEM Study.
AB - INTRODUCTION: Studies on stress distribution around screw retained implants in
different bone densities are limited. In clinical situations crowns of different
heights are placed on the implants and the effect of varying crown implant ratio
on the bone is not understood properly. AIM: To evaluate and compare the stress
distribution in different screw retained implants for different crown-implant
ratios in different bone densities under various occlusal loads using three
dimensional finite element analyses. MATERIALS AND METHODS: In this invitro study
the stress distribution was evaluated and compared between two different crown
heights (7.5mm, 10mm) retained on implants by using different screw materials
(commercially pure titanium, titanium alloy) in two different densities of bone
D2, D3 under various load (100N, 200N) applications by using finite element
analysis. RESULTS: For crown height of 7.5mm, in D2 bone density when vertical
load of 200N was applied, the maximum stress concentration was 1780N/cm(2), for
oblique load of 100N it was 2936N/cm(2) respectively and in D3 bone density when
vertical load of 200N was applied, the maximum stress concentration was
1820N/cm(2), for oblique load of 100N it was 3477N/cm(2) respectively. When the
crown height is increased to 10mm, the maximum stress concentration in D2 bone
was 1875N/cm(2) for vertical load, 4015N/cm(2) for oblique load and in D3 bone
the maximum stress concentration was 2123N/cm(2) for vertical load and 4236N/
cm(2) for oblique load. In case of titanium screws for crown height of 7.5 mm,
when vertical load was applied, stress concentration was 1603 N/cm(2) where as
for titanium alloy screw it was 1820N/cm(2). In case of 10mm crown height stress
concentration was 1904N/cm(2) for titanium screw and 2123N/cm(2) for titanium
alloy screw. In case of oblique loading for 7.5mm crown height stress
concentration was 3155N/cm(2) for titanium screw 3477N/cm(2) for titanium alloy
screw. For 10mm crown height stress concentration was 4236N/cm(2) for titanium
screw, 4663N/cm(2) for titanium alloy screw. CONCLUSION: Stress concentration was
less and stress distribution was better in D2 bone density than in D3 bone
density. Stress concentration was less and stress distribution was better in
commercially pure titanium screw than in titanium alloy screw. With the increase
in the height of crown (i.e., from 7.5mm to 10mm) stress concentration and stress
distribution also increased.
PMID- 27504421
TI - Surgical Re-entry of an Intentionally Replanted Periodontally Compromised Tooth
Treated with Platelet Rich Fibrin (PRF): Hopeless to Hopeful.
AB - Intentional replantation is generally contraindicated in periodontally
compromised teeth however, there are reports suggesting that it can be a
successful treatment alternative for periodontally involved hopeless teeth.
Currently there is dearth of evidence regarding the success of this therapy,
especially evidence for the effectiveness of autologous platelet rich fibrin is
lacking. We present a case report of a 23-year-old male patient with
periodontally hopeless left maxillary central incisor having bone loss extending
beyond root apex. The tooth was gently extracted and replanted utilizing root
conditioning and combined regenerative therapy (Xenograft, PRF and Type I
Collagen Membrane). Surgical re-entry at nine months revealed bone formation in
the apical third of the tooth. At one year, 87% radiographic bone gain was
accomplished. The improvement in the clinical and radiographic parameters
reinforced by the re-entry surgery findings strongly suggest that intentional
replantation may be a cost-effective substitute to implants and tooth supported
prosthesis in situations where conventional periodontal therapy would yield
compromised outcomes.
PMID- 27504422
TI - Clinicopathological and Immunohistochemical Characteristics of Verruciform
Xanthoma of the Lower Gingiva: A Case Report.
AB - Verruciform xanthoma (VX) is a rare benign lesion and mainly effects the oral
mucosa. This slow-growing asymptomatic lesion typically develops along the
gingival margin of the masticatory mucosa, followed by the hard palate, tongue,
buccal mucosa, floor of the mouth, alveolar mucosa, soft palate and junction
between the hard and soft palate. Moreover, this lesion can also affect the skin
and genital organs. Clinically, VX generally presents a sessile or pedunculated
appearance, forming a papule or single plaque with verrucous or papillomatous
mucosal growth. The colour (white, pink, grey, or yellow) depends on the
thickness of the overlying epidermis. In fact, the clinical findings of VX are
similar to those of verrucous carcinoma and other benign tumours, such as
squamous papilloma, verruca vulgaris and mucosal fibroma. For this reason,
clinical and histopathological examinations are essential for accurate
differential diagnosis. Histologically, VX is characterized by parakeratosis,
rete ridges of uniform depth and the accumulation of foam cells, which are also
called "xanthoma cells". Here, we describe the clinicopathological and
immunohistochemical findings of a VX located on the lower gingiva of a 64-year
old male patient.
PMID- 27504423
TI - Zinsser-Cole-Engman Syndrome: A Rare Case Report.
AB - Zinsser-Cole-Engmann syndrome also called Dyskeratosis Congenita (DKC) is a rare
genodermatosis first described by Zinsser in 1906. Mutations in DKC1 gene is
responsible for DKC. It is usually inherited as an X-linked recessive trait,
resulting in a striking male predilection. It is characterized by a triad of
reticular skin pigmentation, nail dystrophy and mucosal leukoplakia.
Complications include predisposition to malignancy and bone marrow failure. Here,
we report a case of DKC in a 9-year-old boy with classic triad of signs. Special
investigations like endoscopy, barium swallow and bone-marrow aspiration study
confirmed the diagnosis. There is no effective treatment for DKC. Some preventive
measures can be adopted and the only long term cure for the haematological
abnormalities is allogenic haemopoietic stem cell transplantation.
PMID- 27504424
TI - A Rare Case of Tamarind Seed Induced Oral Submucous Fibrosis in a 12-Year-Old
Indian Boy.
AB - Oral Submucous Fibrosis (OSMF) is a chronic debilitating, potentially malignant
disorder of the oral cavity. It is characterized by restricted mouth opening
which results due to abnormal accumulation of collagen in the sub-epithelial
layers leading to dense fibrous bands in the mouth. The pathogenesis of the
disease is believed to be multifactorial. However, literature reports suggest a
strong association of OSMF and arecanut chewing habit. The present paper presents
a case of OSMF in a 12-year-old boy without arecanut chewing habit, but with a
heavy practice of chewing tamarind seeds.
PMID- 27504425
TI - Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible.
AB - Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive
tumor that is usually found in the extremities, trunk and infrequently found in
the head and neck area particularly in the jaws, arising from the cells allied
with nerve sheath. Mandibular MPNST may either arise from a preexisting
neurofibroma or develop de novo. Because of the greater variability from case to
case in overall appearance both clinically and histologically, a case of MPNST of
the mandible in a 25-year-old female patient is reported. The lesion was excised
and immunohistological studies (S-100 & Neuron specific enolase) were conducted
to confirm the neural origin.
PMID- 27504426
TI - Mystery behind Non-Healing Wound at Chin Region - Myiasis due to Neglected Trauma
- A Case Report with Review of Literature.
AB - Myiasis is the infestation of human beings with fly larvae which feed on host's
living or dead tissue. Diagnosis of this condition is made by the presence of
larvae in affected body parts. The standard treatment is the mechanical removal
of the maggots from the lesion and management of the general systemic condition.
This paper report a case of myiasis at the chin region in a 45-year-old male
managed by manual removal of larvae after topical application of turpentine oil,
surgical debridement of necrotic tissues and antimicrobial therapy.
PMID- 27504427
TI - An Approach with Hybrid Segmental Mechanics.
AB - Present case report provides an insight into the hybrid segmental mechanics with
treatment of 13-year-old male, considering the side effects of sole continuous
arch wire sliding mechanics. Patient was diagnosed as a case of skeletal class I
jaw relationship, low mandibular plane angle, class II molar relation on right
and class I molar relation on left side, anterior cross bite, crowding of 12mm in
upper, 5mm in lower arch. He also had proclined upper and lower anteriors by 2mm,
convex profile and incompetent lips. Total treatment duration was 20 months,
during which segmental canine retraction was performed with TMA (Titanium,
Molybdenum, Aluminum) 'T' loop retraction spring followed by consolidation of
spaces with continuous arch mechanics. Most of the treatment objectives were met
with good intraoral and facial results within reasonable framework of time. This
approach used traditional twin brackets, which offered the versatility to use
continuous arch-wire mechanics, segmental mechanics and hybrid sectional
mechanics.
PMID- 27504428
TI - Classical Cases of Lymphangioma - As Multiple Vesicular Eruptions.
AB - Lymphangiomas are uncommon congenital hamartomas of the lymphatic system, usually
diagnosed in infancy and early childhood. They are rarely situated in oral cavity
and most commonly identified on the anterior two-thirds of the tongue. Though
rarely seen in the oral cavity, lymphangiomas are the entities which should be
taken into consideration by the clinician while examining vesicular lesions of
the oral cavity. Early recognition is of utmost importance for the initiation of
proper treatment and to avoid serious complications. We hereby report two
classical cases of lymphangioma of the buccal mucosa with multiple vesicular
eruptions, a rare site.
PMID- 27504429
TI - Benign Fibrous Histiocytoma of Mandible: A Case Report and Updated Review.
AB - Benign Fibrous Histiocytoma (BFH) is a well recognised tumour of the soft tissue,
developing entirely within the subcutaneous tissue, the deep soft tissues or in
the parenchymal organs. However, BFH of bones is poorly defined. It has been
rarely reported in the bones with femur, tibia and pelvic bone being the most
commonly affected bones. Involvement of the jawbones is rare. Their clinical and
radiographic features often simulate the common odontogenic and non-odontogenic
lesions of the jaws. Hence, it is imperative for a dentist to have proper
knowledge of various conditions affecting the jaws. Here we report a case of BFH
which presented as an indolent swelling of the right mandibular posterior region
for 15 years. The case emphasizes the need for considering BFH in the
differential diagnosis of swellings of the jaws.
PMID- 27504430
TI - Test Tube Tooth: The Next Big Thing.
AB - Unlike some vertebrates and fishes, humans do not have the capacity for tooth
regeneration after the loss of permanent teeth. Although artificial replacement
with removable dentures, fixed prosthesis and implants is possible through
advances in the field of prosthetic dentistry, it would be ideal to recreate a
third set of natural teeth to replace lost dentition. For many years now,
researchers in the field of tissue engineering have been trying to bioengineer
dental tissues as well as whole teeth. In order to attain a whole tooth through
dental engineering, that has the same or nearly same biological, mechanical and
physical properties of a natural tooth, it's necessary to deal with all the cells
and tissues which are concerned with the formation, maintenance and repair of the
tooth. In this article we review the steps involved in odontogenesis or
organogenesis of a tooth and progress in the bioengineering of a whole tooth.
PMID- 27504431
TI - Prevalence of Periodontal Disease in the General Population of India-A Systematic
Review.
AB - INTRODUCTION: Periodontal disease is a chronic inflammatory disease resulting in
destruction of tissues and structures surrounding the teeth thus, if left
untreated causes loss of teeth and ultimately results in edentulism, posing a
great negative impact on individuals' quality of life. Hence the global
epidemiological data suggests periodontal disease to be one of a major burden on
oral diseases. To reduce this burden it is necessary to know the true prevalence
of the disease according to which proper initiatives can be formulated. India
being home to nearly 1.2 billion people and one amongst the rapidly developing
country, its population requires being systemically as well as orally healthy to
lead a good quality of life. However due to large heterogenecity amongst its
residing population in terms of geographical area, culture, education,
socioeconomic status, a variety of oral diseases like periodontal diseases are
prevalent here. Even though the early studies suggested that the population is
highly susceptible to the disease, the true prevalence of periodontal disease has
not been found yet due to paucity in literature available. AIM: To systematically
review the available literature taken from various parts of India and find the
prevalence rate of periodontal disease amongst the general population of India.
MATERIALS AND METHODS: A literature search was performed using PUB MED, COCHRANE
and EMBASE databases on August 6, 2015. Following full text assessment a thorough
references search was made and potential studies were included. A Quality
assessment of retrieved articles from 2(nd) round was done using a self designed
questionnaire and only field survey studies were included in the systematic
review. RESULTS: The literature search yielded six studies which had performed
field surveys to find the prevalence of periodontal disease in their respective
areas. These studies have observed different sets of age groups and the same has
been accomplished by using Community Periodontal Index (CPI) or Community
Periodontal Index of Treatment Needs (CPITN). It was also found that no
prevalence studies have been carried out in few North and North Eastern states
and Union Territories of India. CONCLUSION: Due to non-availability of same age
groups in selected studies an overall prevalence rate could not be obtained.
However, it was observed that few areas of states like West Bengal, Uttar Pradesh
and Assam have reported a prevalence rate of periodontal disease of more than 85%
in their general population. The data from the present systematic review calls
for a combined initiative from the Government of India and Dental council of
India to have a nationwide multicentric prevalence studies to obtain the true
prevalence rate of periodontal disease in India and interventions should be
provided for the same to maintain the oral health and quality of life of the
affected population.
PMID- 27504432
TI - Certainty of S100 from Physiology to Pathology.
AB - S100 exists in wide variety of tissues and cell types, originally isolated from
brain tissue and they are of low molecular weight proteins. S100 is evenly
distributed in cytoplasm and also in nucleoplasm and is involved in both
intercellular and extracellular functions. S100 protein is generally expressed in
normal and also in pathological conditions. In current review, we discuss: a)
update nomenclature of the various S100 proteins, b) expression of S100 in oral
diseases (different soft tissue tumors, odontogenic cyst and tumor) for
diagnostic value and also to know their histogenesis, c) role of S100 and RAGE
receptor in oral squamous cell carcinoma.
PMID- 27504433
TI - Transposition with Fusion of Maxillary Incisors in Primary Dentition: A Report of
a Rare Case.
PMID- 27504434
TI - Giant Sialolith of Wharton's Duct Treated Economically in a Poor Patient.
PMID- 27504435
TI - Endodontic Management of a Three Rooted Maxillary Premolar: A Report of 3 Cases.
PMID- 27504436
TI - Melanotic Neuroectodermal Tumor of Infancy.
PMID- 27504437
TI - Atypical Response of Gingival Tissue to Extruded Metapex.
PMID- 27504438
TI - Revisited:Association of Serum Cholesterol, Triglyceride, High and Low Density
Lipoprotein (HDL and LDL) Levels in Chronic Periodontitis Subjects with Risk for
Cardiovascular Disease (CVD): A Cross Sectional Study.
PMID- 27504439
TI - Correction.
AB - [This corrects the article DOI: 10.7860/JCDR/2016/18458.7824.].
PMID- 27504440
TI - Abdominal Symptoms and Incident Gallstones in a Population Unaware of Gallstone
Status.
AB - Introduction. Symptoms associated with newly formed gallstones have never been
studied in a population unaware of their gallstones. The objective of this
population-based cohort study was to determine which debut of abdominal symptoms
was associated with newly formed gallstones. Materials and Methods. A cohort
study was performed of a random sample from general population of Copenhagen.
Participants had ultrasound examinations and answered questionnaires about
abdominal symptoms at baseline and two reexaminations over 12 years. Participants
were not informed of gallstone status. Inclusion criteria were no gallstones or
cholecystectomy at baseline and attending a reexamination. Results. Of 3,785
participants, 2,845 fulfilled inclusion criteria. Changes in overall abdominal
pain were not significantly different between incident gallstones or gallstone
free participants. Multiple adjusted logistic regression analyses showed that
incident gallstones were significantly associated with debut of abdominal pain
with projection, localized in the whole upper abdomen, and of longer duration. No
significant associations for functional symptoms were identified. Conclusions. A
new onset of abdominal pain with projection, localized in the whole upper
abdomen, and of longer duration is associated with newly formed gallstones in
participants unaware of gallstone status. Functional symptoms should not be the
indication for surgical treatment.
PMID- 27504442
TI - Slowly Growing Nodule on the Trunk: Cutaneous Granular Cell Tumor.
AB - Granular cell tumor (GCT) is a rare benign neoplasm of the skin that accounts for
0.5% of all soft-tissue tumors. The tumor mostly presents with a symptomatic
slowly growing solitary nodule and overlying normal skin; therefore, it is not
always considered in the differential diagnosis. Here, we report a 58-year-old
female patient who presented with a 4-year history of a slowly growing mass, with
a dimension of 5 * 4 cm on her left waist, diagnosed as a GCT at the
histopathological examination. The neoplastic cells had centrally located nuclei
and granular eosinophilic cytoplasm and stained positively for S100, neuron
specific enolase, and CD68 antibodies. Fifteen months after surgery, the patient
still showed no signs of local recurrence or metastases. Although a large
diameter is a feature of malignant GCT, our case with cutaneous GCT was localized
on the trunk and did not present malignant features clinically and
histopathologically.
PMID- 27504441
TI - Season of Birth Predicts Emotional and Behavioral Regulation in 18-Month-Old
Infants: Hamamatsu Birth Cohort for Mothers and Children (HBC Study).
AB - BACKGROUND: Previous research has demonstrated that the season of birth may
predict development of emotional and behavioral regulation during childhood or
adolescence. This study examined whether the season of birth predicts effortful
control (i.e., the ability to voluntarily choose course of actions during
conflict and to plan for the future) and aggression (i.e., the use of physical
force and expression of anger toward others) in 18-month-old infants. METHODS:
Participants included 885 infants who were enrolled in the Hamamatsu Birth Cohort
for Mothers and Children in Hamamatsu, Japan. Seasons of birth were categorized
into winter (December, January, and February), spring (March, April, and May),
summer (June, July, and August), and autumn (September, October, and November).
At 18 months of age, effortful control was assessed using the Early Childhood
Behavior Questionnaire, and aggression was measured using the Cardiff Infant
Contentiousness Scale. Structural equation modeling analysis with measurement and
structural equations was conducted to test our prediction. RESULTS: Effortful
control was higher in infants born in spring [B = 0.095, 95% CI (0.014 to 0.175),
p = 0.021, beta = 0.146] and summer [B = 0.078, 95% CI (0.001 to 0.156), p =
0.049, beta = 0.118] than in those born in winter. In addition, aggression was
lower in those born in spring [B = -0.286, 95% CI (-0.551 to -0.021), p = 0.035,
beta = -0.135] than those born in winter, even after controlling for seven
covariates. CONCLUSION: The findings suggest that season of birth may determine
development of emotional and behavioral regulation skills during early infancy.
Future research should pay more attention to the underlying mechanisms of the
effects of birth season on development of emotional and behavioral regulation
during infancy.
PMID- 27504443
TI - Bednar Tumor: An Uncommon Entity.
AB - Bednar tumor is an uncommon variant of dermatofibrosarcoma protuberans. Also
known as pigmented dermatofibrosarcoma protuberans, this tumor is of intermediate
grade. It is seen in adults and has a predisposition to affect the shoulder
region. We report a rare case of Bednar tumor in a 40-year-old female patient.
The diagnosis of Bednar tumor must be considered while reporting pigmented
subcutaneous spindle cell lesions.
PMID- 27504444
TI - Paraneoplastic Dermatosis in a Patient with Anaplastic Large-Cell Lymphoma: Case
Report and Literature Review.
AB - BACKGROUND/AIMS: Paraneoplastic dermatoses are skin disorders that are associated
with malignancy. Anaplastic large T-cell lymphoma (ALTCL) has rarely been
associated with paraneoplastic skin manifestations such as gangrenous foot ulcers
and erythroderma. METHODS: We describe a case of ALTCL presenting as a large
annular skin rash. The clinical picture, course, and treatment will be discussed
along with current hypotheses on the mechanism of paraneoplastic syndromes.
RESULTS: Skin manifestations in ALTCL most commonly arise in two distinct ways;
either as primary cutaneous lymphoma manifestation or as systemic disease with
secondary metastasis. Less commonly, systemic disease causes skin manifestations
secondary to a paraneoplastic process without infiltration of malignant cells.
This is thought to be mediated by an immunologic reaction to tumor antigen or the
result of cytokines and other inflammatory markers produced by the tumor itself.
CONCLUSION: Paraneoplastic dermatoses could be the initial presentations of
systemic lymphoma. Knowledge about their association with anaplastic large-cell
lymphoma may help with timely diagnosis. In a patient with unexplained dermatosis
associated with B symptoms who is unresponsive to topic treatment, an
investigation for systemic lymphoma workup is warranted.
PMID- 27504445
TI - Lrig1 Expression in Human Sebaceous Gland Tumors.
AB - BACKGROUND: Sebaceous glands contribute significantly to the barrier functions of
the skin. However, little is known about their homeostasis and tumorigenesis.
Recently, increased expression of stem cell marker Lrig1 has been reported in
sebaceous carcinoma-like tumors of K14DeltaNLef1 transgenic mice. In this study,
we analyzed the Lrig1 expression in human sebaceous tumors. METHODS: Twenty-eight
formalin-fixed paraffin-embedded sebaceous tumor specimens (7 sebaceous
hyperplasias, 7 sebaceous adenomas, 10 sebaceomas and 4 sebaceous carcinomas)
were stained with anti-Lrig1, anti-CD44v3 and anti-Ki67 antibody. RESULTS: Four
(100%) sebaceous carcinomas, 8 (80%) sebaceomas, 3 (43%) sebaceous adenomas and
no sebaceous hyperplasia showed Lrig1 overexpression. DISCUSSION AND CONCLUSION:
Lrig1 is a known tumor suppressor gene and is usually considered to be an
indicator of poorly aggressive tumors. In human sebaceous tumors, the stronger
Lrig1 staining in sebaceous carcinoma compared to other sebaceous tumors might be
a feature of an advanced stage in tumorigenesis and a bad prognosis. In our
study, 100% of sebaceous carcinomas revealed Lrig1 overexpression. We propose
that Lrig1 may be used as a possible new marker of poorly differentiated
sebaceous carcinoma.
PMID- 27504446
TI - A 65-Year-Old Female from Connecticut with Orf Infection.
AB - The virus, which causes orf and induces acute pustular skin lesions in sheep and
goats, is transmissible to humans yet is rarely observed in North America. We
present a case of a 65-year-old female farmer from Connecticut who contracted orf
from her sheep. The clinical and histopathologic features, important to arrive at
the correct diagnosis of this uncommon yet important infection, are described. We
also discuss the benign nature of this condition and emphasize that treatment is
not required.
PMID- 27504447
TI - Injected Hyaluronidase Reduces the Volume of Exogenous Hyaluronate Fillers in
Mice and Results in Clinical Improvement in a Patient with Pretibial Myxedema.
AB - BACKGROUND: Hyaluronidases are essential for the breakdown of hyaluronate (HA) in
tissues and may be used to prevent the adverse effects of HA fillers. OBJECTIVES:
We explored the effect of hyaluronidase on exogenous and endogenous HA in vitro
and in vivo. MATERIALS AND METHODS: HA fillers were incubated with different
concentrations of hyaluronidase and visualized by electrophoresis. HA fillers
were injected in the skin of hairless mice, and 4 h later hyaluronidase was
injected in the papules of exogenous HA. Hyaluronidase was injected in the nodule
of pretibial myxedema of a male patient with Graves' disease. Skin sections of
mice and of the patient were performed, and a skin ultrasound system was used to
monitor the evolution of skin lesions. RESULTS: Hyaluronidase showed a degrading
effect on HA with increasing concentrations. Hyaluronidase injection
significantly decreased the content of exogenous HA within 3 days. Intralesional
injection of hyaluronidase resulted in dissolution of the nodule of pretibial
myxedema with no recurrence during 3 months. CONCLUSION: These results show that
the injection of hyaluronidase is capable of degrading exogenous HA in mouse skin
and endogenous HA in human skin in vivo and may be a therapeutic option for skin
diseases characterized by abnormal accumulation of HA.
PMID- 27504448
TI - Carbon Dioxide Laser Microsurgical Median Glossotomy for Resection of Lingual
Dermoid Cysts.
AB - Dermoid cysts are epithelial-lined cavities with skin adnexae in the capsule.
Only 7% is present in the head and neck. Between 2004 and 2013, four patients
with a lingual dermoid cyst underwent a microsurgical carbon dioxide laser
resection via a median sagittal glossotomy approach. This approach is an elegant
technique combining superior visualization, hemostasis, and little postoperative
edema with good wound healing, allowing for perfect function preservation of the
tongue.
PMID- 27504449
TI - Biology of Saccular Cerebral Aneurysms: A Review of Current Understanding and
Future Directions.
AB - Understanding the biology of intracranial aneurysms is a clinical quandary. How
these aneurysms form, progress, and rupture is poorly understood. Evidence
indicates that well-established risk factors play a critical role, along with
immunologic factors, in their development and clinical outcomes. Much of the
expanding knowledge of the inception, progression, and rupture of intracranial
aneurysms implicates inflammation as a critical mediator of aneurysm
pathogenesis. Thus, therapeutic targets exploiting this arm of aneurysm
pathogenesis have been implemented, often with promising outcomes.
PMID- 27504451
TI - The Current Landscape of Genetic Testing in Cardiovascular Malformations:
Opportunities and Challenges.
AB - Human cardiovascular malformations (CVMs) frequently have a genetic contribution.
Through the application of novel technologies, such as next-generation
sequencing, DNA sequence variants associated with CVMs are being identified at a
rapid pace. While clinicians are now able to offer testing with NGS gene panels
or whole exome sequencing to any patient with a CVM, the interpretation of
genetic variation remains problematic. Variable phenotypic expression, reduced
penetrance, inconsistent phenotyping methods, and the lack of high-throughput
functional testing of variants contribute to these challenges. This article
elaborates critical issues that impact the decision to broadly implement clinical
molecular genetic testing in CVMs. Major benefits of testing include establishing
a genetic diagnosis, facilitating cost-effective screening of family members who
may have subclinical disease, predicting recurrence risk in offsprings, enabling
early diagnosis and anticipatory management of CV and non-CV disease phenotypes,
predicting long-term outcomes, and facilitating the development of novel
therapies aimed at disease improvement or prevention. Limitations include
financial cost, psychosocial cost, and ambiguity of interpretation of results.
Multiplex families and patients with syndromic features are two groups where
disease causation could potentially be firmly established. However, these account
for the minority of the overall CVM population, and there is increasing
recognition that genotypes previously associated with syndromes also exist in
patients who lack non-CV findings. In all circumstances, ongoing dialog between
cardiologists and clinical geneticists will be needed to accurately interpret
genetic testing and improve these patients' health. This may be most effectively
implemented by the creation and support of CV genetics services at centers
committed to pursuing testing for patients.
PMID- 27504450
TI - Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease.
AB - INTRODUCTION: IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that
may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD)
refers to renal lesions associated with IgG4-RD. The most frequent morphological
type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN)
which is associated with increased IgG4-positive plasma cell infiltration and
interstitial fibrosis. CASE REPORT: Herein, we present a rare case with
coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe
tubulointerstitial lesions instead of classic IgG4-TIN. CONCLUSION: IgG4-RKD and
acute crescent glomerulonephritis can occur in the same patient. This case may
give us a clearer viewpoint of the disease.
PMID- 27504452
TI - Mitochondrial Cardiomyopathies.
AB - Mitochondria are found in all nucleated human cells and perform various essential
functions, including the generation of cellular energy. Mitochondria are under
dual genome control. Only a small fraction of their proteins are encoded by
mitochondrial DNA (mtDNA), whereas more than 99% of them are encoded by nuclear
DNA (nDNA). Mutations in mtDNA or mitochondria-related nDNA genes result in
mitochondrial dysfunction leading to insufficient energy production required to
meet the needs for various organs, particularly those with high energy
requirements, including the central nervous system, skeletal and cardiac muscles,
kidneys, liver, and endocrine system. Because cardiac muscles are one of the high
energy demanding tissues, cardiac involvement occurs in mitochondrial diseases
with cardiomyopathies being one of the most frequent cardiac manifestations found
in these disorders. Cardiomyopathy is estimated to occur in 20-40% of children
with mitochondrial diseases. Mitochondrial cardiomyopathies can vary in severity
from asymptomatic status to severe manifestations including heart failure,
arrhythmias, and sudden cardiac death. Hypertrophic cardiomyopathy is the most
common type; however, mitochondrial cardiomyopathies might also present as
dilated, restrictive, left ventricular non-compaction, and histiocytoid
cardiomyopathies. Cardiomyopathies are frequent manifestations of mitochondrial
diseases associated with defects in electron transport chain complexes subunits
and their assembly factors, mitochondrial transfer RNAs, ribosomal RNAs,
ribosomal proteins, translation factors, mtDNA maintenance, and coenzyme Q10
synthesis. Other mitochondrial diseases with cardiomyopathies include Barth
syndrome, Sengers syndrome, TMEM70-related mitochondrial complex V deficiency,
and Friedreich ataxia.
PMID- 27504453
TI - Importance of Quality of Life for Adherence to Sublingual Immunotherapy.
AB - Background. Nonperception of efficacy ranks among the most commonly cited causes
for nonadherence to sublingual immunotherapy (SLIT). Quality of life (QoL) in
patients is a determining factor influencing adherence. We investigated QoL and
adherence separately in SLIT patients at one pediatric practice in Germany.
Methods. We conducted a noninterventional, cross-sectional, retrospective,
quality-of-life survey among pediatric patients treated with SLIT. QoL was
assessed using the generic SF-12 health survey in German. The items contained in
the SF-12 health survey are weighted, added up, and converted to obtain a
physical component score (PCS) and a mental component score (MCS). Each component
score ranges from 0 to 100; the higher the score, the better the QoL perceived.
Results. 201 surveyed patients who had undergone SLIT showed PCS-12 of 49.3 (+/-
7.0) and MCS-12 of 52.6 (+/- 7.2). These figures correlate strongly with those
reported for the German general population (n = 2453): PCS-12 of 49.6 (+/- 8.7)
and MCS-12 of 52.3 (+/- 8.0). 70.2% (73) of 104 patients were adherent at this
practice. Conclusions. QoL in the SLIT patients surveyed here appears as good as
that of the general population. Adherence to SLIT at this practice was remarkably
better than that reported elsewhere.
PMID- 27504454
TI - Heterologous, Expression, and Characterization of Thermostable Glucoamylase
Derived from Aspergillus flavus NSH9 in Pichia pastoris.
AB - A novel thermostable glucoamylase cDNA without starch binding domain (SBD) of
Aspergillus flavus NSH9 was successfully identified, isolated, and overexpressed
in Pichia pastoris GS115. The complete open reading frame of glucoamylase from
Aspergillus flavus NSH9 was identified by employing PCR that encodes 493 amino
acids lacking in the SBD. The first 17 amino acids were presumed to be a signal
peptide. The cDNA was cloned into Pichia pastoris and the highest expression of
recombinant glucoamylase (rGA) was observed after 8 days of incubation period
with 1% methanol. The molecular weight of the purified rGA was about 78 kDa and
exhibited optimum catalytic activity at pH 5.0 and temperature of 70 degrees C.
The enzyme was stable at higher temperature with 50% of residual activity
observed after 20 min at 90 degrees C and 100 degrees C. Low concentration of
metal (Mg(++), Fe(++), Zn(++), Cu(++), and Pb(++)) had positive effect on rGA
activity. This rGA has the potential for use and application in the
saccharification steps, due to its thermostability, in the starch processing
industries.
PMID- 27504455
TI - Effects of Erythropoietin Administration on Adrenal Glands of Landrace/Large
White Pigs after Ventricular Fibrillation.
AB - Aim. To evaluate the effects of erythropoietin administration on the adrenal
glands in a swine model of ventricular fibrillation and resuscitation. Methods.
Ventricular fibrillation was induced via pacing wire forwarded into the right
ventricle in 20 female Landrace/Large White pigs, allocated into 2 groups:
experimental group treated with bolus dose of erythropoietin (EPO) and control
group which received normal saline. Cardiopulmonary resuscitation (CPR) was
performed immediately after drug administration as per the 2010 European
Resuscitation Council (ERC) guidelines for Advanced Life Support (ALS) until
return of spontaneous circulation (ROSC) or death. Animals who achieved ROSC were
monitored, mechanically ventilated, extubated, observed, and euthanized. At
necroscopy, adrenal glands samples were formalin-fixed, paraffin-embedded, and
routinely processed. Sections were stained with hematoxylin-eosin. Results.
Oedema and apoptosis were the most frequent histological changes and were
detected in all animals in the adrenal cortex and in the medulla. Mild and focal
endothelial lesions were also detected. A marked interindividual variability in
the degree of the intensity of apoptosis and oedema at cortical and medullary
level was observed within groups. Comparing the two groups, higher levels of
pathological changes were detected in the control group. No significant
difference between the two groups was observed regarding the endothelial changes.
Conclusions. In animals exposed to ventricular fibrillation, EPO treatment has
protective effects on the adrenal gland.
PMID- 27504456
TI - "Slalom": Microsurgical Cross-Over Decompression for Multilevel Degenerative
Lumbar Stenosis.
AB - Objective. Selective, bilateral multisegmental microsurgical decompression of
lumbar spinal canal stenosis through separate, alternating cross-over approaches.
Indications. Two-segmental and multisegmental degenerative central and lateral
lumbar spinal stenosis. Contraindications. None. Surgical Technique. Minimally
invasive, muscle, and facet joint-sparing bilateral decompression of the lumbar
spinal canal through 2 or more alternating microsurgical cross-over approaches
from one side. Results. From December 2010 until December 2015 we operated on 202
patients with 2 or multisegmental stenosis (115 f; 87 m; average age 69.3 yrs,
range 51-91 yrs). All patients were suffering from symptoms typical of a
degenerative lumbar spinal stenosis. All patients complained about back pain;
however the leg symptoms were dominant in all cases. Per decompressed segment,
the average OR time was 36 min and the blood loss 45.7 cc. Patients were
mobilized 6 hrs postop and hospitalization averaged 5.9 days. A total of 116/202
patients did not need submuscular drainage. 27/202 patients suffered from a
complication (13.4%). Dural tears occurred in 3.5%, an epidural hematoma in 5.5%,
a deep wound infection in 1.98%, and a temporary radiculopathy postop in 1.5%.
Postop follow-up ranged from 12 to 24 months. There was a significant improvement
of EQ 5 D, Oswestry Disability Index (ODI), VAS for Back and Leg Pain, and
preoperative standing times and walking distances.
PMID- 27504457
TI - Systematic Analysis of the Cytokine and Anhedonia Response to Peripheral
Lipopolysaccharide Administration in Rats.
AB - Inflammatory processes may cause depression in subsets of vulnerable individuals.
Inflammation-associated behavioral changes are commonly modelled in rodents by
administration of bacterial lipopolysaccharide (LPS). However, the time frame in
which immune activation and depressive-like behavior occur is not very clear. In
this study, we showed that systemic administration of LPS robustly increased
circulating levels of corticosterone, leptin, pro- and anti-inflammatory
cytokines, and chemokines. Serum concentrations of most analytes peaked within
the first 6 h after LPS injection and returned to baseline values by 24 h.
Chemokine levels, however, remained elevated for up to 96 h. Using an optimized
sucrose preference test (SPT) we showed that sickness behavior was present from 2
to 24 h. LPS-induced anhedonia, as measured by decreased sucrose preference,
lasted up to 96 h. To mimic the human situation, where depression develops after
chronic inflammation, rats were preexposed to repeated LPS administration or
subchronic restraint stress and subsequently challenged with LPS. While these
procedures did not increase the duration of anhedonia, our results do indicate
that inflammation may cause depressive symptoms such as anhedonia. Using our SPT
protocol, more elaborate rodent models can be developed to study the mechanisms
underlying inflammation-associated depression in humans.
PMID- 27504458
TI - Association between Serum Albumin Concentration and Ketosis Risk in Hospitalized
Individuals with Type 2 Diabetes Mellitus.
AB - Objective. This study examined the association between serum albumin
concentration and ketosis risk in hospitalized individuals with type 2 diabetes
mellitus (T2DM). Methods. A retrospective cross-sectional study was conducted at
a medical center in Taiwan. Inclusion criteria were endocrinology ward inpatients
exceeding 21 years of age, with preexisting diagnosis of T2DM, and blood glucose
above 13.9 millimoles per liter (mmol/L) at admission. Individuals without
measurement of serum albumin, urine ketone, or hemoglobin A1C, or harboring
active infection, myocardial infarction, cerebrovascular event, cirrhosis,
malignancy, or overt proteinuria were excluded. Using serum albumin concentration
below 3.0 grams per deciliter to define hypoalbuminemia, 151 hypoalbuminemic
cases and 104 normoalbuminemic controls were enrolled. The presence of ketones in
urine established ketosis. Results. The prevalence of ketonuria was 48% in
hypoalbuminemic subjects compared to 30% in normoalbuminemic controls (odds ratio
(OR): 2.15; 95% confidence interval (CI): 1.26-3.57; P = 0.004). Moreover, among
the 156 subjects with serum beta-hydroxybutyrate measurement in addition to urine
ketone, 33% of the hypoalbuminemic individuals had ketonemia exceeding 3 mmol/L
compared to 19% of those with normoalbuminemia (OR: 2.12, 95% CI: 0.99-4.48, P =
0.051). Conclusions. Serum albumin concentration is inversely associated with
ketosis risk in hospitalized individuals with T2DM.
PMID- 27504459
TI - Small Mouse Islets Are Deficient in Glucagon-Producing Alpha Cells but Rich in
Somatostatin-Secreting Delta Cells.
AB - Small and big mouse islets were compared with special reference to their content
of glucagon-producing alpha-cells and somatostatin-producing delta-cells. Areas
stained for glucagon and somatostatin were measured in the largest cross section
of small (diameter < 60 MUm) and big (diameter > 100 MUm) islets. Comparison of
the areas indicated proportionally more delta- than alpha-cells in the small
islets. After isolation with collagenase these islets were practically devoid of
alpha-cells. We evaluated the functional importance of the islet size by
measuring the Ca(2+) signal for insulin release. A majority of the small islets
responded to the hyperpolarization action of somatostatin with periodic decrease
of cytoplasmic Ca(2+) when glucose was elevated after tolbutamide blockade of the
KATP channels.
PMID- 27504462
TI - An Uncommon Association of Familial Partial Lipodystrophy, Dilated
Cardiomyopathy, and Conduction System Disease.
AB - A 46-year-old African American woman presented with severe respiratory distress
requiring intubation and was diagnosed with nonischemic cardiomyopathy. She had
the typical phenotype of familial partial lipodystrophy 2 (FPLD2). Sequence
analysis of LMNA gene showed a heterozygous missense mutation at exon 8
(c.1444C>T) causing amino acid change, p.R482W. She later developed severe
coronary artery disease requiring multiple percutaneous coronary interventions
and coronary artery bypass surgery. She was later diagnosed with diabetes,
primary hyperparathyroidism, and euthyroid multinodular goiter. She had sinus
nodal and atrioventricular nodal disease and had an implantable cardioverter
defibrillator implantation due to persistent left ventricular dysfunction. The
device eroded through the skin few months after implantation and needed a re
implant on the contralateral side. She had atrial flutter requiring ablation.
This patient with FPLD2 had most of the reported cardiac complications of FPLD2.
This case is presented to improve the awareness of the presentation of this
disease among cardiologists and internists.
PMID- 27504460
TI - Impact of the Type of Continuous Insulin Administration on Metabolism in a
Diabetic Rat Model.
AB - Exogenous insulin is the only treatment available for type 1 diabetic patients
and is mostly administered by subcutaneous (SC) injection in a basal and bolus
scheme using insulin pens (injection) or pumps (preimplanted SC catheter). Some
divergence exists between these two modes of administration, since pumps provide
better glycaemic control compared to injections in humans. The aim of this study
was to compare the impacts of two modes of insulin administration (single
injections of long-acting insulin or pump delivery of rapid-acting insulin) at
the same dosage (4 IU/200 g/day) on rat metabolism and tissues. The rat weight
and blood glucose levels were measured periodically after treatment.
Immunostaining for signs of oxidative stress and for macrophages was performed on
the liver and omental tissues. The continuous insulin delivery by pumps restored
normoglycaemia, which induced the reduction of both reactive oxygen species and
macrophage infiltration into the liver and omentum. Injections controlled the
glucose levels for only a short period of time and therefore tissue stress and
inflammation were elevated. In conclusion, the insulin administration mode has a
crucial impact on rat metabolic parameters, which has to be taken into account
when studies are designed.
PMID- 27504461
TI - Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on
the Scientific Point of View.
AB - Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular
disorders in both children and adults which can progress to end-stage renal
failure. Although there are genetic and secondary causes, circulating factors
have also been regarded as an important factor in the pathogenesis of FSGS,
because about 40% of the patients with FSGS have recurrence after renal
transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is
a soluble form of uPAR, which is a membrane-bound protein linked to GPI in
various immunologically active cells, including podocytes. It has recently been
suggested as a potential circulating factor in FSGS by in vitro podocyte
experiments, in vivo mice models, and human studies. However, there have also
been controversies on this issue, because subsequent studies showed conflicting
results. suPAR levels were also increased in patients with other glomerular
diseases and were inversely correlated with estimated glomerular filtration rate.
Nevertheless, there has been no balanced review on this issue. In this review, we
compare the conflicting data on the involvement of suPAR in the pathogenesis of
FSGS and shed light on interpretation by taking into account many points and the
potential variables and confounders influencing serum suPAR levels.
PMID- 27504464
TI - Epidemiology of Operative Procedures in an NCAA Division I Football Team Over 10
Seasons.
AB - BACKGROUND: Injury rates are high for collegiate football players. Few studies
have evaluated the epidemiology of surgical procedures in National Collegiate
Athletic Association (NCAA) Division I collegiate football players. PURPOSE: To
determine the most common surgical procedures performed in collegiate football
players over a 10-year period. STUDY DESIGN: Descriptive epidemiological study.
METHODS: From the 2004-2005 season through the 2013-2014 season, all surgical
procedures performed on athletes from a single NCAA Division I college football
team during athletic participation were reviewed. Surgeries were categorized by
anatomic location, and operative reports were used to obtain further surgical
details. Data collected over this 10-season span included type of injury, primary
procedures, reoperations, and cause of reoperation, all categorized by specific
anatomic locations and position played. RESULTS: From the 2004-2005 through the
2013-2014 seasons, 254 operations were performed on 207 players, averaging 25.4
surgical procedures per year. The majority of surgeries performed were
orthopaedic procedures (92.1%, n = 234). However, there were multiple
nonorthopaedic procedures (7.9%, n = 20). The most common procedure performed was
arthroscopic shoulder labral repair (12.2%, n = 31). Partial meniscectomy (11.8%,
n = 30), arthroscopic anterior cruciate ligament (ACL) reconstruction (9.4% n =
24), and arthroscopic hip labral repair (5.9% n = 15) were the other commonly
performed procedures. There were a total of 29 reoperations performed; thus,
12.9% of primary procedures had a reoperation. The most common revision procedure
was a revision open reduction internal fixation of stress fractures in the foot
as a result of a symptomatic nonunion (33.33%, n = 4) and revision ACL
reconstruction (12.5%, n = 3). By position, relative to the number of athletes at
each position, linebackers (30.5%) and defensive linemen (29.1%) were the most
likely to undergo surgery while kickers (6%) were the least likely. CONCLUSION:
In NCAA Division I college football players, the most commonly performed
surgeries conducted for injuries were orthopaedic in nature. Of these,
arthroscopic shoulder labral repair was the most common, followed closely by
partial meniscectomy. Nonorthopaedic procedures nonetheless accounted for a
sizable portion of surgical volume. Familiarity with this injury and surgical
spectrum is of utmost importance for the team physician treating these high-level
contact athletes.
PMID- 27504463
TI - Fibular Strut Graft Augmentation for Open Reduction and Internal Fixation of
Proximal Humerus Fractures: A Systematic Review and the Authors' Preferred
Surgical Technique.
AB - BACKGROUND: Proximal humerus fractures are common problems plaguing the elderly
population. PURPOSE: The purposes of this study were to determine the outcomes of
fibular strut allografts in treatment of proximal humerus fractures with open
reduction internal fixation (ORIF) and to present the authors' preferred surgical
technique. The hypothesis was that the use of fibular strut allografts in
treating proximal humerus fractures with ORIF will provide low reoperation rates
with acceptable outcomes. STUDY DESIGN: Systematic review; Level of evidence, 4.
METHODS: A systematic review was registered with PROSPERO and performed with
PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses)
guidelines using 3 publicly available free databases. Therapeutic clinical
outcome investigations reporting arthroscopic elbow outcomes with levels of
evidence 1 through 4 were eligible for inclusion. All study, subject, and
surgical technique demographics were analyzed and compared between continents and
countries. Statistics were calculated using Student t tests, 1-way analysis of
variance, chi-square tests, and 2-proportion Z tests. RESULTS: Four studies met
the inclusion criteria. While there is great heterogeneity existing in the
literature surrounding use of a fibular strut allograft as an adjunct to ORIF of
proximal humerus fractures, current evidence shows a humeral head screw
penetration rate of 3.7% with acceptable functional outcome scores, with a
reoperation rate of 4.4% at a weighted mean 80.78 weeks (1.55 years) of
postoperative follow-up. CONCLUSION: There is great heterogeneity that exists in
the literature surrounding the use of a fibular strut allograft as an adjunct to
ORIF of proximal humerus fractures. Current evidence shows a screw penetration
rate of 3.7% with acceptable functional outcome scores, demonstrating fibular
strut allograft is a viable option for treating proximal humerus fractures.
PMID- 27504465
TI - Kinematics of Shooting in High School and Collegiate Lacrosse Players With and
Without Low Back Pain.
AB - BACKGROUND: Low back pain (LBP) and motion alterations can occur in athletes who
engage in high-speed throwing motions. The relationship between LBP and shooting
motion in lacrosse players is not yet known. PURPOSE: To quantify the effects of
LBP on key kinematic parameters of the lacrosse shot and determine the
contribution of the severity of LBP on specific kinematic parameters of the
shooting motion. STUDY DESIGN: Controlled laboratory study. METHODS: High school
and collegiate players (N = 24) were stratified into 2 groups based on back pain
symptoms (LBP or no pain). Three-dimensional motion capture of overhead throws
was used to collect data on knee, pelvis, trunk, and shoulder kinematics as well
as crosse stick (the stick capped with a strung net) and ball speed. RESULTS:
Mean low back numeric pain rating scale (NRSpain) score was 2.9. Knee flexion at
ball release was greater in the LBP than no pain group, indicating a more bent
knee (P = .04). The LBP group demonstrated less angular velocity transfer from
pelvis to trunk than the no pain group (P = .05). Total range of motion of the
pelvis and shoulders during the shot and follow-through were less in the LBP
group than the no pain group (83.6 degrees +/- 24.5 degrees vs 75.9 degrees +/
24.5 degrees , P = .05). Age- and sex-adjusted regression analyses revealed that
the low back NRSpain rating contributed 6.3% to 25.0% of the variance to the
models of shoulder transverse rotation range of motion, trunk and shoulder
rotation angular velocities, and knee flexion angle (P < .05). CONCLUSION: LBP
severity significantly contributes to trunk and shoulder motion restriction
during lacrosse shooting. Inclusion of lumbopelvic and core training and
prehabilitation programs for high school and collegiate players may reduce pain
in affected players as well as help them to attain appropriate motion parameters
and avoid secondary musculoskeletal injuries. CLINICAL RELEVANCE: This research
identified a prehabilitation need in the understudied lacrosse population.
Therapeutic strategies can be developed to strengthen the throwing motion, which
could control mechanical loading patterns on the low back and minimize pain
symptoms in players with chronic LBP.
PMID- 27504466
TI - Closed-Loop Double Endobutton Technique for Repair of Unstable Distal Clavicle
Fractures.
AB - BACKGROUND: Displaced fractures of the distal clavicle are inherently unstable
and lead to nonunion in a high percentage of cases. The optimal surgical
management remains controversial. HYPOTHESIS: Indirect osteosynthesis with a
closed-loop double endobutton construct would result in reliable fracture union
and obviate the need for additional surgery. STUDY DESIGN: Case series; Level of
evidence, 4. METHODS: Eight patients with an acute unstable Neer type IIB distal
clavicle fracture were treated with a closed-loop double endobutton implant. Mean
follow-up averaged 3.4 years (range, 1-9 years). Two patients were lost to follow
up. The remaining 6 patients underwent a detailed functional and radiologic
evaluation. RESULTS: Definitive fracture healing was achieved in all patients.
There were no complications, and no patients required additional surgery related
to the index procedure. The mean Constant score was 97 at final follow-up.
CONCLUSION: The closed-loop double endobutton technique was reliable and
effective in achieving fracture union in all patients with unstable Neer type IIB
fractures of the distal clavicle. This technique obviates the need for late
hardware removal that is often necessary when direct osteosynthesis is used and
avoids potential complications associated with coracoclavicular cerclage
constructs that require knot fixation.
PMID- 27504467
TI - Meniscal Ramp Lesions: Anatomy, Incidence, Diagnosis, and Treatment.
AB - Meniscal ramp lesions are more frequently associated with anterior cruciate
ligament (ACL) injuries than previously recognized. Some authors suggest that
this entity results from disruption of the meniscotibial ligaments of the
posterior horn of the medial meniscus, whereas others support the idea that it is
created by a tear of the peripheral attachment of the posterior horn of the
medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to
have a low sensitivity, and consequently, ramp lesions often go undiagnosed.
Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of
the posterior horn of the medial meniscus should be performed. Several treatment
options have been reported, including nonsurgical management, inside-out meniscal
repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a
standard meniscal repair rehabilitation protocol should be followed. However,
when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation
should follow the designated ACLR postoperative protocol. The purpose of this
article was to review the current literature regarding meniscal ramp lesions and
summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended
treatment options, and postoperative protocol.
PMID- 27504468
TI - Comparison of Short-term Complications Between 2 Methods of Coracoclavicular
Ligament Reconstruction: A Multicenter Study.
AB - BACKGROUND: Numerous techniques have been used to treat acromioclavicular (AC)
joint dislocation, with anatomic reconstruction of the coracoclavicular (CC)
ligaments becoming a popular method of fixation. Anatomic CC ligament
reconstruction is commonly performed with cortical fixation buttons (CFBs) or
tendon grafts (TGs). PURPOSE: To report and compare short-term complications
associated with AC joint stabilization procedures using CFBs or TGs. STUDY
DESIGN: Cohort study; Level of evidence, 3. METHODS: We conducted a retrospective
review of the operative treatment of AC joint injuries between April 2007 and
January 2013 at 2 institutions. Thirty-eight patients who had undergone a
procedure for AC joint instability were evaluated. In these 38 patients with a
mean age of 36.2 years, 18 shoulders underwent fixation using the CFB technique
and 20 shoulders underwent reconstruction using the TG technique. RESULTS: The
overall complication rate was 42.1% (16/38). There were 11 complications in the
18 patients in the CFB group (61.1%), including 7 construct failures resulting in
a loss of reduction. The most common mode of failure was suture breakage (n = 3),
followed by button migration (n = 2) and coracoid fracture (n = 2). There were 5
complications in the TG group (25%), including 3 cases of asymptomatic
subluxation, 1 symptomatic suture granuloma, and 1 superficial infection. There
were no instances of construct failure seen in TG fixations. CFB fixation was
found to have a statistically significant increase in complications (P = .0243)
and construct failure (P = .002) compared with TG fixation. CONCLUSION: CFB
fixation was associated with a higher rate of failure and higher rate of early
complications when compared with TG fixation.
PMID- 27504469
TI - Regulation of proliferation and histone acetylation in embryonic neural
precursors by CREB/CREM signaling.
AB - The transcription factor CREB (cAMP-response element binding protein) regulates
differentiation, migration, survival and activity-dependent gene expression in
the developing and mature nervous system. However, its specific role in the
proliferation of embryonic neural progenitors is still not completely understood.
Here we investigated how CREB regulates proliferation of mouse embryonic neural
progenitors by a conditional mutant lacking Creb gene in neural progenitors. In
parallel, we explored possible compensatory effects by the genetic ablation of
another member of the same gene family, the cAMP-responsive element modulator
(Crem). We show that CREB loss differentially impaired the proliferation,
clonogenic potential and self-renewal of precursors derived from the ganglionic
eminence (GE), in comparison to those derived from the cortex. This phenotype was
associated with a specific reduction of histone acetylation in the GE of CREB
mutant mice, and this reduction was rescued in vivo by inhibition of histone
deacetylation. These observations indicate that the impaired proliferation could
be caused by a reduced acetyltransferase activity in Creb conditional knock-out
mice. These findings support a crucial role of CREB in controlling embryonic
neurogenesis and propose a novel mechanism by which CREB regulates embryonic
neural development.
PMID- 27504470
TI - Radial glia in the proliferative ventricular zone of the embryonic and adult
turtle, Trachemys scripta elegans.
AB - To better understand the role of radial glial (RG) cells in the evolution of the
mammalian cerebral cortex, we investigated the role of RG cells in the dorsal
cortex and dorsal ventricular ridge of the turtle, Trachemys scripta elegans.
Unlike mammals, the glial architecture of adult reptile consists mainly of
ependymoradial glia, which share features with mammalian RG cells, and which may
contribute to neurogenesis that continues throughout the lifespan of the turtle.
To evaluate the morphology and proliferative capacity of ependymoradial glia
(here referred to as RG cells) in the dorsal cortex of embryonic and adult
turtle, we adapted the cortical electroporation technique, commonly used in
rodents, to the turtle telencephalon. Here, we demonstrate the morphological and
functional characteristics of RG cells in the developing turtle dorsal cortex. We
show that cell division occurs both at the ventricle and away from the ventricle,
that RG cells undergo division at the ventricle during neurogenic stages of
development, and that mitotic Tbr2+ precursor cells, a hallmark of the mammalian
SVZ, are present in the turtle cortex. In the adult turtle, we show that RG cells
encompass a morphologically heterogeneous population, particularly in the
subpallium where proliferation is most prevalent. One RG subtype is similar to RG
cells in the developing mammalian cortex, while 2 other RG subtypes appear to be
distinct from those seen in mammal. We propose that the different subtypes of RG
cells in the adult turtle perform distinct functions.
PMID- 27504471
TI - Characterization of Np95 expression in mouse brain from embryo to adult: A novel
marker for proliferating neural stem/precursor cells.
AB - Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90) plays an important
role in maintaining DNA methylation of newly synthesized DNA strands by
recruiting DNA methyltransferase 1 (DNMT1) during cell division. In addition,
Np95 participates in chromatin remodeling by interacting with histone
modification enzymes such as histone deacetylases. However, its expression
pattern and function in the brain have not been analyzed extensively. We here
investigated the expression pattern of Np95 in the mouse brain, from
developmental to adult stages. In the fetal brain, Np95 is abundantly expressed
at the midgestational stage, when a large number of neural stem/precursor cells
(NS/PCs) exist. Interestingly, Np95 is expressed specifically in NS/PCs but not
in differentiated cells such as neurons or glial cells. Furthermore, we
demonstrate that Np95 is preferentially expressed in type 2a cells, which are
highly proliferative NS/PCs in the dentate gyrus of the adult hippocampus.
Moreover, the number of Np95-expressing cells increases in response to kainic
acid administration or to voluntary running, which are known to enhance the
proliferation of adult NS/PCs. These results suggest that Np95 participates in
the process of proliferation and differentiation of NS/PCs, and that it should be
a useful novel marker for proliferating NS/PCs, facilitating the analysis of the
complex behavior of NS/PCs in the brain.
PMID- 27504472
TI - MicroRNAs of the miR379-410 cluster: New players in embryonic neurogenesis and
regulators of neuronal function.
AB - The imprinted miR379-410 cluster contains 38 microRNAs (miRNAs) that are involved
in diverse neurodevelopmental processes and are important regulators of neuronal
function. The implications of these miRNAs in neurological diseases have been
recently recognized.In the present minireview, the current findings regarding the
brain-specific functions of miR379-410 cluster miRNAs are summarized and
discussed.
PMID- 27504473
TI - Identification and expression patterns of novel long non-coding RNAs in neural
progenitors of the developing mammalian cortex.
AB - Long non-coding (lnc)RNAs play key roles in many biological processes.
Elucidating the function of lncRNAs in cell type specification during organ
development requires knowledge about their expression in individual progenitor
types rather than in whole tissues. To achieve this during cortical development,
we used a dual-reporter mouse line to isolate coexisting proliferating neural
stem cells, differentiating neurogenic progenitors and newborn neurons and
assessed the expression of lncRNAs by paired-end, high-throughput sequencing. We
identified 379 genomic loci encoding novel lncRNAs and performed a comprehensive
assessment of cell-specific expression patterns for all, annotated and novel,
lncRNAs described to date. Our study provides a powerful new resource for
studying these elusive transcripts during stem cell commitment and neurogenesis.
PMID- 27504474
TI - Role of dual energy spectral computed tomography in characterization of
hepatocellular carcinoma: Initial experience from a tertiary liver care
institute.
AB - OBJECTIVE: To investigate dual-energy spectral CT in characterization of
hepatocellular Carcinoma (HCC) in patients with chronic liver disease. METHODS:
Dynamic computed tomography (CT) was performed in 3600 patients (2879 males; 721
females, mean age 50.9 +/- 11.9 years) with working clinical diagnosis of liver
cirrhosis for hepatocellular carcinoma screening and other clinical indications.
The study was conducted over a period of 3 years. During dynamic CT scanning,
spectral (monochromatic) and routine (polychromatic) CT acquisitions were
obtained on a single tube, dual energy, 64 slice multi-detector CT scanner.
Imaging findings were studied on routine CT. On the basis of routine CT findings,
indeterminate lesions (lesions not showing characteristic hypervascularity
followed by washout on dynamic routine CT scan) that were referred for biopsy or
surgery were segregated. A retrospective blinded review of the lesions, acquired
by the spectral CT acquisitions was done with the help of gem stone imaging (GSI)
software to characterize these lesions. All the above lesions were analyzed
qualitatively in the arterial phase for lesion conspicuity as well as
quantitatively using the monochromatic data sets and nodule Iodine concentration
on material density maps, respectively. This data was studied with respect to
predictability of HCC using the spectral CT technique. Iodine density of the
lesion, surrounding liver parenchyma, and lesion to liver parenchyma ratio (LLR)
were derived and statistically analyzed. Histopathology of the lesion in question
was treated as gold standard for analysis. RESULTS: It was observed via
statistical analysis that the value of iodine density of the lesion on material
density sets of >=29.5 mg/dl, enabled a discriminatory power of 86.5%,
sensitivity of 90.5% with 95% confidence Interval (CI) (69.2-98.8%) and
specificity of 81.2% with 95% Confidence Interval (54.4-95.9%) in predicting HCC.
Qualitative assessment also showed higher lesion conspicuity with spectral CT
image sets as compared to routine CT data. CONCLUSION: This study reveals that
spectral imaging is an excellent qualitative as well as a quantitative tool for
assessing and predicting hepatocellular carcinoma in cirrhotic patients.
PMID- 27504475
TI - From first to latest imaging technology: Revisiting the first mummy investigated
with X-ray in 1896 by using dual-source computed tomography.
AB - PURPOSE: The aim of this study was to systematically reinvestigate the first
human mummy that was ever analyzed with X-ray imaging in 1896, using dual-source
computed tomography (DSCT) in order to compare the earliest and latest imaging
technologies, to estimate preservation, age at death, sex, anatomical variants,
paleopathological findings, mummification, embalming and wrapping of the child
mummy from ancient Egypt. Radiocarbon dating was used to determine the mummy's
age and to specify the child's living period in the Egyptian chronology. MATERIAL
AND METHODS: The ancient Egyptian child mummy is kept in the Senckenberg Museum
of Natural History in Frankfurt am Main, Germany. An accelerator mass
spectrometer (MICADAS) was used for radiocarbon dating. DSCT was performed using
a 2 * 64 slice dual-source CT system (Siemens Healthineers, Forchheim, Germany).
A thorough visual examination of the mummy, a systematic radiological evaluation
of the DICOM datasets, and established methods in physical anthropology were
applied to assess the bio-anthropological data and the post mortem treatment of
the body. RESULTS: Radiocarbon dating yielded a calibrated age between 378 and
235 cal BC (95.4% confidence interval), corresponding with the beginning of the
Ptolemaic period. The mummy was a male who was four to five years old at the time
of death. Remnants of the brain and inner organs were preserved by the embalmers,
which is regularly observed in ancient Egyptian child mummies. Skin tissue, inner
organs, tendons and/or musculature, cartilage, nerves and vasculature could be
identified on the DSCT dataset. The dental health of the child was excellent.
Anatomical variants and pathological defects included a congenital Pectus
excavatum deformity, hepatomegaly, Harris lines, and longitudinal clefts in the
ventral cortices of both femora. CONCLUSION: Our results highlight the enormous
progress achieved form earliest to latest imaging technology for advanced mummy
research using the first human mummy investigated with X-ray. With the
application of DSCT, detailed knowledge regarding age at death, sex, diseases,
death, and mummification of a child from Ptolemaic Egypt are revealed while
considering the temporary rites of body treatment and burial for children.
PMID- 27504476
TI - Intra-individual diagnostic image quality and organ-specific-radiation dose
comparison between spiral cCT with iterative image reconstruction and z-axis
automated tube current modulation and sequential cCT.
AB - OBJECTIVES: To prospectively evaluate image quality and organ-specific-radiation
dose of spiral cranial CT (cCT) combined with automated tube current modulation
(ATCM) and iterative image reconstruction (IR) in comparison to sequential tilted
cCT reconstructed with filtered back projection (FBP) without ATCM. METHODS: 31
patients with a previous performed tilted non-contrast enhanced sequential cCT
aquisition on a 4-slice CT system with only FBP reconstruction and no ATCM were
prospectively enrolled in this study for a clinical indicated cCT scan. All
spiral cCT examinations were performed on a 3rd generation dual-source CT system
using ATCM in z-axis direction. Images were reconstructed using both, FBP and IR
(level 1-5). A Monte-Carlo-simulation-based analysis was used to compare organ
specific-radiation dose. Subjective image quality for various anatomic structures
was evaluated using a 4-point Likert-scale and objective image quality was
evaluated by comparing signal-to-noise ratios (SNR). RESULTS: Spiral cCT led to a
significantly lower (p < 0.05) organ-specific-radiation dose in all targets
including eye lense. Subjective image quality of spiral cCT datasets with an IR
reconstruction level 5 was rated significantly higher compared to the sequential
cCT acquisitions (p < 0.0001). Consecutive mean SNR was significantly higher in
all spiral datasets (FBP, IR 1-5) when compared to sequential cCT with a mean SNR
improvement of 44.77% (p < 0.0001). CONCLUSIONS: Spiral cCT combined with ATCM
and IR allows for significant-radiation dose reduction including a reduce eye
lens organ-dose when compared to a tilted sequential cCT while improving
subjective and objective image quality.
PMID- 27504477
TI - Data on the impact of SSRIs and depression symptoms on the neural activities in
obsessive-compulsive disorder at rest.
AB - The data provided here related to our research article (Chen et al., 2016) [1].
We provide whole-brain intrinsic functional connectivity patterns in obsessive
compulsive disorder at resting-state [1]. This article also provides
supplementary information to our research article, i.e., between - group
comparisons of the effect of selective serotonin reuptake inhibitors (SSRIs) and
combined depression symptoms on resting-state neural activities in obsessive
compulsive disorder. The data presented here provide novel insights into the
effect of SSRIs and combined depression symptoms on the neural activities at
rest.
PMID- 27504478
TI - Extraction of phenolic compounds from extra virgin olive oil by a natural deep
eutectic solvent: Data on UV absorption of the extracts.
AB - This data article refers to the paper "Towards green analysis of virgin olive oil
phenolic compounds: extraction by a natural deep eutectic solvent and direct
spectrophotometric detection" [1]. A deep eutectic solvent (DES) based on lactic
acid and glucose was used as green solvent for phenolic compounds. Eight standard
phenolic compounds were solubilized in the DES. Then, a set of extra virgin olive
oil (EVOO) samples (n=65) were submitted to liquid-liquid extraction by the DES.
The standard solutions and the extracts were analyzed by UV spectrophotometry.
This article reports the spectral data of both the standard solutions and the 65
extracts, as well as the total phenolic content of the corresponding oils,
assessed by the Folin-Ciocalteu assay.
PMID- 27504480
TI - Sclerosing sweat duct carcinoma of the lower extremity treated with Mohs
micrographic surgery.
PMID- 27504479
TI - Perianal streptococcal infection precipitating pustular psoriasis in an adult.
PMID- 27504481
TI - Bullous leukemia cutis in a patient with T-cell prolymphocytic leukemia.
PMID- 27504482
TI - Pembrolizumab-associated sarcoidosis.
PMID- 27504483
TI - Case series: The use of a dehydrated human amnion/chorion membrane allograft to
enhance healing in the repair of lower eyelid defects after Mohs micrographic
surgery.
PMID- 27504484
TI - Muscle Activation Differs between Three Different Knee Joint-Angle Positions
during a Maximal Isometric Back Squat Exercise.
AB - The purpose of this study was to compare muscle activation of the lower limb
muscles when performing a maximal isometric back squat exercise over three
different positions. Fifteen young, healthy, resistance-trained men performed an
isometric back squat at three knee joint angles (20 degrees , 90 degrees , and
140 degrees ) in a randomized, counterbalanced fashion. Surface electromyography
was used to measure muscle activation of the vastus lateralis (VL), vastus
medialis (VM), rectus femoris (RF), biceps femoris (BF), semitendinosus (ST), and
gluteus maximus (GM). In general, muscle activity was the highest at 90 degrees
for the three quadriceps muscles, yet differences in muscle activation between
knee angles were muscle specific. Activity of the GM was significantly greater at
20 degrees and 90 degrees compared to 140 degrees . The BF and ST displayed
similar activation at all joint angles. In conclusion, knee position alters
muscles activation of the quadriceps and gluteus maximus muscles. An isometric
back squat at 90 degrees generates the highest overall muscle activation, yet an
isometric back squat at 140 degrees generates the lowest overall muscle
activation of the VL and GM only.
PMID- 27504485
TI - A Scoping Review of the Associations of Golf with Eye Injuries in Adults and
Children.
AB - Introduction. Sport presents a risk of ocular trauma and accounts for a
significant number of eye injuries that require hospital admission. The sport of
golf presents a risk to eyesight from fast moving objects such as golf clubs and
balls. This study aims to investigate the associations of golf with eye injuries
and the reasons that these injuries occur. Material/Methods. A literature search
was conducted using the databases MEDLINE, Web of Science, SPORTDiscus, and
PsycINFO. Grey literature was searched using the WHO international clinical
trials registry platform, Google Scholar, and ProQuest. Data was extracted using
a standardised form and summarised into a report. Results and Discussion. Twenty
three studies were found relating to eye injuries in golf. Injuries appear to be
rare, but more frequent in men and children. Injuries resulted in high rates of
enucleation and visual impairment. Children sustained more injury from golf clubs
whereas adults sustained more injuries from golf balls. Conclusion. Efforts are
needed to encourage golf participants to understand the risks of ocular and
indeed other head injuries. Initiatives to provide appropriate supervision and
education on this topic are merited. Further research is needed to investigate
the circumstances of eye injury in golf and assess the effects of interventions
aimed at reducing risk of injury.
PMID- 27504486
TI - Future Perspectives of ERAS: A Narrative Review on the New Applications of an
Established Approach.
AB - ERAS approach (Enhanced Recovery After Surgery) is a multimodal, perioperative
pathway designed to achieve early recovery after surgery. ERAS has shown
documented efficacy in elective surgery, and the concept of "multimodal" and
"multidisciplinary" approach seems still to be of higher importance than each
single item within ERAS protocols. New perspectives include the use of ERAS in
emergency surgery, where efficacy and safety on outcome have been documented, and
flexibility of traditional items may add benefits for traditionally high-risk
patients. Obstetric surgery, as well, may open wide horizons for future research,
since extremely poor data are currently available, and ERAS benefits may
translate even on the baby. Finally, the concept of "outcome" may be extended
when considering the specific setting of cancer surgery, in which variables like
cancer recurrence, early access to adjuvant therapies, and, finally, long-term
survival are as important as the reduced perioperative complications. In this
perspective, different items within ERAS protocols should be reinterpreted and
eventually integrated towards "protective" techniques, to develop cancer-specific
ERAS approaches keeping pace with the specific aims of oncologic surgery.
PMID- 27504487
TI - Exercise Your Brain.
PMID- 27504488
TI - A Conversation with Amy Clippinger.
PMID- 27504489
TI - Does Nanomedicine Have a Delivery Problem?
PMID- 27504490
TI - Protein Calligraphy: A New Concept Begins To Take Shape.
AB - The ability to assemble molecules into supramolecular architectures of
controllable size and symmetry is a long sought after goal of nanotechnology and
material engineering. Proteins are particularly attractive for molecular assembly
due to their inherent molecular recognition and self-assembly capabilities.
Advances in the computational prediction of protein folding and quaternary
assembly have enabled the design of proteins that self-assemble into complex yet
predictable shapes. These protein nanostructures are opening new possibilities in
biomaterials, metabolic engineering, molecular delivery, tissue engineering, and
a plethora of nanomaterials. Images of protein constructs assembled from simpler
structures draw comparison to characters of calligraphy. In both cases, elaborate
designs emerge from basic subunits, resulting in the translation of form into
function with a high degree of artistry.
PMID- 27504491
TI - Deciphering the Interplay among Multisite Phosphorylation, Interaction Dynamics,
and Conformational Transitions in a Tripartite Protein System.
AB - Multisite phosphorylation is a common pathway to regulate protein function,
activity, and interaction pattern in vivo, but routine biochemical analysis is
often insufficient to identify the number and order of individual phosphorylation
reactions and their mechanistic impact on the protein behavior. Here, we
integrate complementary mass spectrometry (MS)-based approaches to characterize a
multisite phosphorylation-regulated protein system comprising Polo-like kinase 1
(Plk1) and its coactivators Aurora kinase A (Aur-A) and Bora, the interplay of
which is essential for mitotic entry after DNA damage-induced cell cycle arrest.
Native MS and cross-linking-MS revealed that Aur-A/Bora-mediated Plk1 activation
is accompanied by the formation of Aur-A/Bora and Plk1/Bora heterodimers. We
found that the Aur-A/Bora interaction is independent of the Bora phosphorylation
state, whereas the Plk1/Bora interaction is dependent on extensive Bora multisite
phosphorylation. Bottom-up and top-down proteomics analyses showed that Bora
multisite phosphorylation proceeds via a well-ordered sequence of site-specific
phosphorylation reactions, whereby we could reveal the involvement of up to 16
phosphorylated Bora residues. Ion mobility spectrometry-MS demonstrated that this
multisite phosphorylation primes a substantial structural rearrangement of Bora,
explaining the interdependence between extensive Bora multisite phosphorylation
and Plk1/Bora complex formation. These results represent a first benchmark of our
multipronged MS strategy, highlighting its potential to elucidate the mechanistic
and structural implications of multisite protein phosphorylation.
PMID- 27504492
TI - Reconstitution and Functional Analysis of a Full-Length Hepatitis C Virus NS5B
Polymerase on a Supported Lipid Bilayer.
AB - Therapeutic targeting of membrane-associated viral proteins is complicated by the
challenge of investigating their enzymatic activities in the native membrane
bound state. To permit functional characterization of these proteins, we
hypothesized that the supported lipid bilayer (SLB) can support in situ
reconstitution of membrane-associated viral protein complexes. As proof-of
principle, we selected the hepatitis C virus (HCV) NS5B polymerase which is
essential for HCV genome replication, and determined that the SLB platform
enables functional reconstitution of membrane protein activity. Quartz crystal
microbalance with dissipation (QCM-D) monitoring enabled label-free detection of
full-length NS5B membrane association, its interaction with replicase subunits
NS3, NS5A, and template RNA, and most importantly its RNA synthesis activity.
This latter activity could be inhibited by the addition of candidate small
molecule drugs. Collectively, our results demonstrate that the SLB platform can
support functional studies of membrane-associated viral proteins engaged in
critical biological activities.
PMID- 27504493
TI - Morphologies Observed in Ultraflexible Microemulsions with and without the
Presence of a Strong Acid.
AB - We show that three different morphologies exist near the two-phase boundary of
ternary systems containing a hydrotropic cosolvent. Based on synchrotron small-
and wide-angle X-ray scattering combined with molecular dynamics, we rationalize
the specific scattering signature of direct, bicontinuous, and reverse mesoscale
solubilization. Surprisingly, these mesostructures are resilient toward strong
acids, which are required in industrial applications. However, on a macroscopic
scale, the phase boundary shifts in salting-in and salting-out in the direct and
respectively reverse regime, leading to a crossing of the binodals.
PMID- 27504494
TI - In Vivo Bioorthogonal Chemistry Enables Local Hydrogel and Systemic Pro-Drug To
Treat Soft Tissue Sarcoma.
AB - The ability to activate drugs only at desired locations avoiding systemic
immunosuppression and other dose limiting toxicities is highly desirable. Here we
present a new approach, named local drug activation, that uses bioorthogonal
chemistry to concentrate and activate systemic small molecules at a location of
choice. This method is independent of endogenous cellular or environmental
markers and only depends on the presence of a preimplanted biomaterial near a
desired site (e.g., tumor). We demonstrate the clear therapeutic benefit with
minimal side effects of this approach in mice over systemic therapy using a
doxorubicin pro-drug against xenograft tumors of a type of soft tissue sarcoma
(HT1080).
PMID- 27504495
TI - Complex relation of HLA-DRB1*1501, age at menarche, and age at multiple sclerosis
onset.
AB - OBJECTIVE: To examine the relationship between 2 markers of early multiple
sclerosis (MS) onset, 1 genetic (HLA-DRB1*1501) and 1 experiential (early
menarche), in 2 cohorts. METHODS: We included 540 white women with MS or
clinically isolated syndrome (N = 156 with genetic data available) and 1,390
white women without MS but with a first-degree relative with MS (Genes and
Environment in Multiple Sclerosis [GEMS]). Age at menarche, HLA-DRB1*1501 status,
and age at MS onset were analyzed. RESULTS: In both cohorts, participants with at
least 1 HLA-DRB1*1501 allele had a later age at menarche than did participants
with no risk alleles (MS: mean difference = 0.49, 95% confidence interval [CI] =
[0.03-0.95], p = 0.036; GEMS: mean difference = 0.159, 95% CI = [0.012-0.305], p
= 0.034). This association remained after we adjusted for body mass index at age
18 (available in GEMS) and for other MS risk alleles, as well as a single
nucleotide polymorphism near the HLA-A region previously associated with age of
menarche (available in MS cohort). Confirming previously reported associations,
in our MS cohort, every year decrease in age at menarche was associated with a
0.65-year earlier MS onset (95% CI = [0.07-1.22], p = 0.027, N = 540). Earlier MS
onset was also found in individuals with at least 1 HLA-DRB1*1501 risk allele
(mean difference = -3.40 years, 95% CI = [-6.42 to -0.37], p = 0.028, N = 156).
CONCLUSIONS: In 2 cohorts, a genetic marker for earlier MS onset (HLA-DRB1*1501)
was inversely related to earlier menarche, an experiential marker for earlier
symptom onset. This finding warrants broader investigations into the association
between the HLA region and hormonal regulation in determining the onset of
autoimmune disease.
PMID- 27504496
TI - Trans-pQTL study identifies immune crosstalk between Parkinson and Alzheimer
loci.
AB - OBJECTIVE: Given evidence from genetic studies, we hypothesized that there may be
a shared component to the role of myeloid function in Parkinson and Alzheimer
disease (PD and AD) and assessed whether PD susceptibility variants influenced
protein expression of well-established AD-associated myeloid genes in human
monocytes. METHODS: We repurposed data in which AD-related myeloid proteins CD33,
TREM1, TREM2, TREML2, TYROBP, and PTK2B were measured by flow cytometry in
monocytes from 176 participants of the PhenoGenetic Project (PGP) and Harvard
Aging Brain Study. Linear regression was used to identify associations between 24
PD risk variants and protein expression. The 2 cohorts were meta-analyzed in a
discovery analysis, and the 4 most strongly suggestive results were validated in
an independent cohort of 50 PGP participants. RESULTS: We discovered and
validated an association between the PD risk allele rs12456492(G) in the RIT2
locus and increased CD33 expression (p joint = 3.50 * 10(-5)) and found strongly
suggestive evidence that rs11060180(A) in the CCDC62/HIP1R locus decreased PTK2B
expression (p joint = 1.12 * 10(-4)). Furthermore, in older individuals,
increased CD33 expression on peripheral monocytes was associated with a greater
burden of parkinsonism (p = 0.047), particularly bradykinesia (p = 6.64 * 10(
3)). CONCLUSIONS: We find that the rs12456492 PD risk variant affects expression
of AD-associated protein CD33 in peripheral monocytes, which suggests that
genetic factors for these 2 diseases may converge to influence overlapping innate
immune-mediated mechanisms that contribute to neurodegeneration. Furthermore, the
effect of the rs12456492(G) PD risk allele on increased CD33 suggests that the
inhibition of certain myeloid functions may contribute to PD susceptibility, as
is the case for AD.
PMID- 27504497
TI - Env7p Associates with the Golgin Protein Imh1 at the trans-Golgi Network in
Candida albicans.
AB - Vesicular dynamics is one of the very important aspects of cellular physiology,
an imbalance of which leads to the disorders or diseases in higher eukaryotes. We
report the functional characterization of a palmitoylated protein kinase from
Candida albicans whose homologue in Saccharomyces cerevisiae has been reported to
be involved in negative regulation of membrane fusion and was named Env7.
However, the downstream target of this protein remains to be identified. Env7 in
C. albicans (CaEnv7) could be isolated from the membrane fraction and localized
to vesicular structures associated with the Golgi apparatus. Our work reports
Env7 in C. albicans as a new player involved in maintaining the functional
dynamics at the trans-Golgi network (TGN) by interacting with two other TGN
resident proteins, namely, Imh1p and Arl1p. Direct interaction could be detected
between Env7p and the golgin protein Imh1p. Env7 is itself phosphorylated (Env7p)
and phosphorylates Imh1 in vivo. An interaction between Env7 and Imh1 is required
for the targeted localization of Imh1. CaEnv7 has a putative palmitoylation site
toward both N and C termini. An N-terminal palmitoylation-defective strain
retains its ability to phosphorylate Imh1 in vitro. An ENV7 homozygous mutant
showed compromised filamentation in solid media and attenuated virulence, whereas
an overexpressed strain affected cell wall integrity. Thus, Env7 plays a subtle
but important role at the level of multitier regulation that exists at the TGN.
IMPORTANCE A multitier regulation exists at the trans-Golgi network in all higher
organisms. We report a palmitoylated protein kinase, Env7, that functions at the
TGN interface by interacting with two more TGN-resident proteins, namely, Imh1
and Arl1. Palmitoylation seems to be important for the specific localization.
This study focuses on the involvement of a ubiquitous protein kinase, whose
substrates had not yet been reported from any organism, as an upstream signaling
component that modulates the activity of the Imh1-Arl1 complex crucial for
maintaining membrane asymmetry. Virulence is significantly diminished in an Env7
mutant. The functioning of this protein in C. albicans seems to be quite
different from its nearest homologue in S. cerervisiae, which reflects the
evolutionary divergence between these two organisms.
PMID- 27504498
TI - Replacement of Glycoprotein B in Alcelaphine Herpesvirus 1 by Its Ovine
Herpesvirus 2 Homolog : Implications in Vaccine Development for Sheep-Associated
Malignant Catarrhal Fever.
AB - Vaccine development is a top priority in malignant catarrhal fever (MCF)
research. In the case of sheep-associated MCF (SA-MCF) caused by ovine
herpesvirus 2 (OvHV-2), progress toward this objective has been hindered by the
absence of methods to attenuate or modify the virus, since it cannot be
propagated in vitro. As an alternative for vaccine development, in this study, we
tested the hypothesis that one of the SA-MCF vaccine candidate targets, OvHV-2
glycoprotein B (gB), could be expressed by a nonpathogenic alcelaphine
herpesvirus 1 (AlHV-1) and then evaluated the potential of the AlHV-1/OvHV-2
chimera to be used as a vaccine and a diagnostic tool. The construction and
characterization of an AlHV-1/OvHV-2 chimeric virus that is nonpathogenic and
expresses an OvHV-2 vaccine target are significant steps toward the development
of an SA-MCF vaccine and also provide a valuable means to study OvHV-2 biology.
PMID- 27504499
TI - First Detection of Bat White-Nose Syndrome in Western North America.
AB - White-nose syndrome (WNS) is an emerging fungal disease of bats caused by
Pseudogymnoascus destructans. Since it was first detected near Albany, NY, in
2006, the fungus has spread across eastern North America, killing unprecedented
numbers of hibernating bats. The devastating impacts of WNS on Nearctic bat
species are attributed to the likely introduction of P. destructans from Eurasia
to naive host populations in eastern North America. Since 2006, the disease has
spread in a gradual wavelike pattern consistent with introduction of the pathogen
at a single location. Here, we describe the first detection of P. destructans in
western North America in a little brown bat (Myotis lucifugus) from near Seattle,
WA, far from the previously recognized geographic distribution of the fungus.
Whole-genome sequencing and phylogenetic analyses indicated that the isolate of
P. destructans from Washington grouped with other isolates of a presumed clonal
lineage from the eastern United States. Thus, the occurrence of P. destructans in
Washington does not likely represent a novel introduction of the fungus from
Eurasia, and the lack of intensive surveillance in the western United States
makes it difficult to interpret whether the occurrence of P. destructans in the
Pacific Northwest is disjunct from that in eastern North America. Although there
is uncertainty surrounding the impacts of WNS in the Pacific Northwest, the
presence of the pathogen in western North America could have major consequences
for bat conservation. IMPORTANCE White-nose syndrome (WNS) represents one of the
most consequential wildlife diseases of modern times. Since it was first
documented in New York in 2006, the disease has killed millions of bats and
threatens several formerly abundant species with extirpation or extinction. The
spread of WNS in eastern North America has been relatively gradual, inducing
optimism that disease mitigation strategies could be established in time to
conserve bats susceptible to WNS in western North America. The recent detection
of the fungus that causes WNS in the Pacific Northwest, far from its previous
known distribution, increases the urgency for understanding the long-term impacts
of this disease and for developing strategies to conserve imperiled bat species.
PMID- 27504500
TI - Impact of Education on School-aged Children's Knowledge of and Participation in
"The Choking Game".
AB - OBJECTIVES: To better understand school-aged children's awareness of and
attitudes about the Choking Game (TCG). To determine if education can increase
awareness of the risk of injury when playing TCG and to determine if education
can decrease interest in TCG participation. DESIGN: Anonymous pre- and post
education surveys. SETTING: Two middle/high schools; one in Utah and one in
California. SUBJECTS: 291 participants (163 in Utah, 128 in California) aged 9
18, 68% under age 15, 32% 15 and older; 65% white, 35% non-white; 52% female, 48%
male. RESULTS: 76% of participants knew about TCG, of those 62% heard about it at
school. 32% knew someone who had played, and twelve (4%) had played, usually with
others. Most frequently cited as reasons for participation were curiosity, peer
pressure, and competition. School was the most common location for playing. In
California education significantly increased risk awareness, and significant
positive attitude changes were observed regarding interest in playing TCG. Utah
participants also exhibited attitude changes in the desired direction (less
interest in playing TCG, would warn friends, and realized it was not safe to stop
breathing), although results were not statistically significant, possibly due to
previous education and four recent and highly publicized TCG deaths in the
community. CONCLUSION: Results indicate that interactive, standardized, and
skills-based education can increase student awareness of TCG risks and decrease
interest in participation. Students reported that the schools were often where
they first heard about TCG and where TCG was commonly played. Educators and
associated health care professionals should therefore be encouraged to provide
preventative education as part of school curricula.
PMID- 27504506
TI - A molecularly imprinted electrochemiluminescence sensor based on the mimetic
enzyme catalytic effect for ultra-trace Ni2+ determination.
AB - A novel molecularly imprinted polymer (MIP) electrochemiluminescence (MIP-ECL)
sensor was developed for the highly sensitive and selective determination of
ultra-trace levels of Ni2+. The complex Ni2+-dimethylglyoxime (Ni-DMG) was chosen
as the template molecule to construct the MIP and then acted as a mimetic enzyme
to catalyse the oxidisation of luminol to enhance the ECL signal. When the
imprinted cavities were occupied by Ni-DMG in the rebinding process, the ECL
intensities produced by the luminol-H2O2 ECL system on the MIP-modified electrode
surface increased with increased concentration of the Ni-DMG complex. The highly
sensitive determination of Ni2+ was achieved through a catalytic reaction. This
technique could be used for the quantitative analysis of Ni2+ with concentrations
from 3.0 * 10-12 mol L-1 to 6.0 * 10-9 mol L-1. The detection limit was 1.01 * 10
12 mol L-1, which is much lower than that reported previously. In addition, the
allowable amounts of interference ions in the MIP-ECL sensor were higher than
that in other common molecularly imprinted sensors because of its excellent
recognition of 3D cavity-to-complex molecules and ligand-to-metal ions. This
method was successfully used to determine Ni2+ in real samples, such as apples,
carrots and grapes, and has been proven feasible for practical applications.
PMID- 27504507
TI - To the Editor.
PMID- 27504508
TI - Fate of Australia's wildlife in the balance.
PMID- 27504509
TI - Q & A: Hugh Dickinson.
PMID- 27504510
TI - In memoriam Peter Mazur--cryobiologist.
PMID- 27504511
TI - Letter to the Editor. Re: "Acute pancreatitis as the first manifestation of
duodenal MALT lymphoma" by Ivona Simkova et al. Biomed Pap Med Fac Univ Palacky
Olomouc Czech Repub 2015;159(4):688-94. doi: 10.5507/bp.2015.047.
PMID- 27504512
TI - Comment on the letter from the author Vitorino Modesto dos Santos.
PMID- 27504513
TI - Introduction to the Special Issue on Celebrating the 50th Anniversary of the
Allan Variance.
PMID- 27504514
TI - Mechanisms of Corneal Pain and Implications for Postoperative Pain After Laser
Correction of Refractive Errors.
AB - OBJECTIVE: The cornea is the target of most surgeries for refractive disorders,
as myopia. It is estimated that almost 1 million patients undergo corneal
refractive surgery each year in the United States. Refractive surgery includes
photorefractive keratectomy (PRK) that produces intense postoperative pain. This
review presents the main pain mechanisms behind PRK-related pain and the
available therapeutic options for its management. METHODS: Data sources included
literature of cornea anatomy, treatment of PRK postoperative pain, mechanisms of
corneal pain, in 3 electronic databases: Pubmed, Scopus, and Web of Science. Only
double-blinded controlled trials on pain control after PRK were selected to show
the endpoints, treatment, and control strategies. RESULTS: A total of 18 double
blind, controlled trials were identified. These studies have shown the use of
topical nonsteroidal anti-inflammatory drugs, topical steroidal anti-inflammatory
drugs, systemic analgesics, cold balanced saline solution, topical anesthetic,
gabapentin, and morphine to treat postoperative pain in PRK. DISCUSSION: The
percentage of responders has seldom been reported, and few studies allow for the
formal calculation of the number necessary to treat. Postoperative intense pain
after PRK laser surgery remains the main challenge to its widespread use for the
correction of refractive errors.
PMID- 27504516
TI - Biological roles of milk osteopontin.
AB - PURPOSE OF REVIEW: Osteopontin (OPN) is an extensively phosphorylated acidic
glycoprotein that is present at high concentration in human milk. Bovine milk OPN
has recently become commercially available, and can thus be added to infant
formula as well as other food products. Studies in experimental animals as well
as a clinical trial in human infants reveal important biological roles for milk
OPN. RECENT FINDINGS: Newborn wild-type mice nursing knock-out dams lacking milk
OPN showed impaired cognitive development, reduced brain OPN and myelin-related
proteins as compared with pups nursing wild-type dams. Transcriptomic analysis of
intestinal biopsies from infant rhesus monkeys fed formula with added bovine milk
OPN showed that OPN positively regulated intestinal proliferation, cell
migration, and cellular chemotaxis via binding to integrin receptors. A clinical
trial on human infants fed formula with added bovine milk OPN showed
significantly reduced levels of serum tumor necrosis factor a and fewer days of
fever as compared with infants fed regular formula. Further, their immune cell
profile was more similar to that of breast-fed infants. SUMMARY: Milk OPN affects
immune functions, and intestinal development in the newborn as well as brain
development in a mouse model. Addition of bovine milk OPN to infant formula may
improve the performance of formula-fed infants and make them more similar to
breast-fed infants. Due to its multiple functions, milk OPN is also used for
various adult applications.
PMID- 27504517
TI - Nutrition in the preterm infant: what's new?
AB - PURPOSE OF REVIEW: The increasing recognition of the role of nutritional care for
preterm infants continues to result in a proliferation of review articles,
systematic reviews, observational studies and trials. In this article, we review
a selection of important studies published in the last 12-18 months. RECENT
FINDINGS: The selected studies demonstrate the potential importance of light
protecting parenteral nutrition solutions, the benefits of standardized
concentrated parenteral nutrition solutions and the importance of insulin-like
growth factor I in early life. Trials of immunonutrients (such as bile salt
stimulated lipase) and other bioactive peptides such as lactoferrin are in
progress, and emerging data highlight the importance of vitamin D for immune
regulation, and therefore its role in sepsis and gut function. Early oro
pharyngeal administration of colostrum appears to safely improve early immune
development, and supports the increasingly common practice of immediate
commencement of mothers' own breast milk. Despite this, studies continue to show
that breastfeeding continuation rates could be improved. Data also highlight the
potential role of macronutrient supply on other functional outcomes, such as
retinopathy of prematurity. Finally, the importance of the unique nutritional
needs of late and moderately preterm infants is starting to be recognized - a
much larger group than the extremely preterm infants in whom many studies are
focused. SUMMARY: Earlier, more aggressive nutrient supply and feeding regimes,
including optimal support of breastfeeding mothers to ensure adequate provision
of own mother's milk, appear to improve growth and neurodevelopmental outcomes.
The addition of bioactive proteins shows promise. Special focus needs to be
reestablished for late and moderately preterm infants, who have particular
nutritional and feeding support requirements. This review has highlighted the
need for further research particularly in the areas of early parenteral
nutrition, the optimal regime to improve early growth and neuronal effects, the
optimal rate of growth and/or catch-up, and the role of immune nutrients.
PMID- 27504518
TI - [Germany joins the Nagoya Protocol: campaign against biopiracy].
PMID- 27504519
TI - [Prevention of pedophilia: therapy for more than 500 men].
PMID- 27504520
TI - [Announcement: palliative care specialty congress].
PMID- 27504521
TI - [Staffing in nursing homes now being negotiated: a new "nursing care need"
concept leads to increased personnel costs].
PMID- 27504522
TI - [Nurses must make a greater effort to adapt to migrants: study shows deficits in
culturally sensitive nursing].
PMID- 27504523
TI - [Ethics board: patient welfare in the hospital falls by the wayside: due to
economization no time is left for communication].
PMID- 27504524
TI - [Addiction in the elderly: new information for nurses].
PMID- 27504525
TI - Single-Molecule Rotational Switch on a Dangling Bond Dimer Bearing.
AB - One of the key challenges in the construction of atomic-scale circuits and
molecular machines is to design molecular rotors and switches by controlling the
linear or rotational movement of a molecule while preserving its intrinsic
electronic properties. Here, we demonstrate both the continuous rotational
switching and the controlled step-by-step single switching of a trinaphthylene
molecule adsorbed on a dangling bond dimer created on a hydrogen-passivated
Ge(001):H surface. The molecular switch is on-surface assembled when the covalent
bonds between the molecule and the dangling bond dimer are controllably broken,
and the molecule is attached to the dimer by long-range van der Waals
interactions. In this configuration, the molecule retains its intrinsic
electronic properties, as confirmed by combined scanning tunneling
microscopy/spectroscopy (STM/STS) measurements, density functional theory
calculations, and advanced STM image calculations. Continuous switching of the
molecule is initiated by vibronic excitations when the electrons are tunneling
through the lowest unoccupied molecular orbital state of the molecule. The
switching path is a combination of a sliding and rotation motion over the
dangling bond dimer pivot. By carefully selecting the STM conditions, control
over discrete single switching events is also achieved. Combined with the ability
to create dangling bond dimers with atomic precision, the controlled rotational
molecular switch is expected to be a crucial building block for more complex
surface atomic-scale devices.
PMID- 27504526
TI - A multi-rater framework for studying personality: The trait-reputation-identity
model.
AB - Personality and social psychology have historically been divided between
personality researchers who study the impact of traits and social-cognitive
researchers who study errors in trait judgments. However, a broader view of
personality incorporates not only individual differences in underlying traits but
also individual differences in the distinct ways a person's personality is
construed by oneself and by others. Such unique insights are likely to appear in
the idiosyncratic personality judgments that raters make and are likely to have
etiologies and causal force independent of trait perceptions shared across
raters. Drawing on the logic of the Johari window (Luft & Ingham, 1955), the Self
Other Knowledge Asymmetry Model (Vazire, 2010), and Socioanalytic Theory (Hogan,
1996; Hogan & Blickle, 2013), we present a new model that separates personality
variance into consensus about underlying traits (Trait), unique self-perceptions
(Identity), and impressions conveyed to others that are distinct from self
perceptions (Reputation). We provide three demonstrations of how this Trait
Reputation-Identity (TRI) Model can be used to understand (a) consensus and
discrepancies across rating sources, (b) personality's links with self-evaluation
and self-presentation, and (c) gender differences in traits. We conclude by
discussing how researchers can use the TRI Model to achieve a more sophisticated
view of personality's impact on life outcomes, developmental trajectories,
genetic origins, person-situation interactions, and stereotyped judgments.
(PsycINFO Database Record
PMID- 27504527
TI - Synthesis of the Acyclic Carbon Skeleton of Filipin III.
AB - The synthesis of the carbon skeleton of filipin III, a polyenic macrolactone
possessing 11 stereogenic centers, was achieved using a convergent strategy with
the longest linear sequence of 19 steps starting from hexanal. Construction of
the polyene was realized using two successive Heck couplings as the key steps.
Control of the stereogenic centers of the polyol fragment was performed by
utilizing an Evans aldolization, a 1,3-syn aldolization, enantio- and
diastereoselective allylations, a hemiacetalization/oxa-Michael sequence, and a
1,3-syn reduction. The polyol and polyenic fragments were coupled using a 1,5
anti diastereoselective aldolization followed by a 1,3-anti reduction.
PMID- 27504528
TI - Multimodality Imaging of Neurodegenerative Processes: Part 2, Atypical Dementias.
AB - OBJECTIVE: The purpose of this article is to describe the role of multimodality
imaging in the evaluation of atypical neurodegenerative conditions. An imaging
approach to the more common dementia disease processes was described in part 1.
This article, part 2, briefly discusses current Centers for Medicare & Medicaid
Services coverage for imaging patients with dementia and illustrates the basic
concepts of combining anatomic, metabolic, and amyloid imaging in the evaluation
of patients with atypical neurodegenerative dementia. Although these disease
processes are rare, the growing repertoire of clinically available imaging
techniques necessitates an understanding of their imaging patterns. CONCLUSION:
Despite the rarity of these conditions, imaging of patients with
neurodegenerative disorders is on the rise, and familiarity with the imaging
appearances of these atypical causes is increasingly important.
PMID- 27504529
TI - Solution to the pi-Distortivity Problem.
AB - Traditionally, the delocalized pi system of benzene is believed to be responsible
for its perfectly symmetric D6h geometry. However, it has also been suggested
that the pi system prefers a distorted D3h geometry. Arguments for this have been
based on clever use of VB methods as well as through shifts in the frequency of
the distortive b2u mode. Evidence has been provided through different ways of
partitioning the total electronic energy between the sigma and the pi systems.
These methods are plagued by the fact that there is no unique way to partition
the energy, leading to questions regarding the validity of the conclusions. Here
we note that even though energy cannot be partitioned exactly, force acting on a
nucleus depends only on the single particle density and can hence be partitioned
exactly. Using good-quality wave functions that are numerically found to obey the
Hellmann-Feynman theorem to good accuracy, we calculate the sigma and pi
components of the force and provide conclusive evidence of pi-distortivity at the
HF level. Our approach provides an unambiguous way to approach the problem with
wave functions that account for electron correlation. Our calculations suggest
that the conclusion is valid at the MP2 level, too.
PMID- 27504530
TI - Lichenoid drug eruption caused by clonazepam.
PMID- 27504531
TI - Tissue Reaction to a Novel Bone Substitute Material Fabricated With Biodegradable
Polymer-Calcium Phosphate Nanoparticle Composite.
AB - PURPOSE: The aim of this study was to evaluate the effectiveness of a novel bone
substitute material fabricated using a biodegradable polymer-calcium phosphate
nanoparticle composite. METHODS: Porous structured poly-L-lactic acid (PLLA) and
hydroxyapatite (HA) nanoparticle composite, which was fabricated using solid
liquid phase separation and freeze-drying methods, was grafted into bone defects
created in rat calvarium or tibia. Rats were killed 4 weeks after surgery, and
histological analyses were performed to evaluate new bone formation. RESULTS:
Scanning electron microscopic observation showed the interconnecting pores within
the material and the pore diameter was approximately 100 to 300 MUm. HA
nanoparticles were observed to be embedded into the PLLA beams. In the calvarial
implantation model, abundant blood vessels and fibroblastic cells were observed
penetrating into pores, and in the tibia model, newly formed bone was present
around and within the composite. CONCLUSIONS: The PLLA-HA nanoparticle composite
bone substitute developed in this study showed biocompatibility, elasticity, and
operability and thus has potential as a novel bone substitute.
PMID- 27504532
TI - Growth Factors in Bone Marrow Blood of the Mandible With Application of
Extracorporeal Shock Wave Therapy.
AB - INTRODUCTION: Enhancement of bone regeneration is crucial to dental implantology.
Growth factors play a significant role during osteogenesis and angiogenesis.
Extracorporeal shock wave therapy (ESWT) enhances bone healing; however, no
studies have yet been performed in oral implantology. MATERIALS AND METHODS:
Twenty patients who underwent bilateral mandibular wisdom tooth removal were
included. ESWT was applied to 1 side of the jaw. Blood samples were collected
from the peripheral vein (PB), mandibular bone marrow without and with ESWT (BM
/+SW). Quantity and quality of the growth factors bone morphogenetic protein
(BMP)-2, BMP-4, insulin-like growth factor 1 (IGF-1), vascular endothelial growth
factor (VEGF), and transforming growth factor-beta (TGF-beta) were investigated
via ELISA and cell proliferation assay. RESULTS: ELISA revealed superior amounts
of IGF-1 and VEGF in BM-/+SW compared to PB (P < 0.05). TGF-beta demonstrated no
variance. Levels of BMP-2 and BMP-4 were too low for adequate detection in the
ELISA. No difference was noticed upon ESWT. The cell proliferation assay did not
identify any changes comparing PB versus BM-SW versus BM + SW. CONCLUSION: IGF-1
and VEGF are present at higher levels in mandibular bone marrow than in
peripheral blood (PB). This study did not identify any benefits of extracorporeal
shock wave therapy to increase the investigated growth factors.
PMID- 27504533
TI - Periimplantitis Treatment: Long-Term Comparison of Laser Decontamination and
Implantoplasty Surgery.
AB - PURPOSE: Periimplantitis is the most frequent cause of late implant failure;
however, little is known about the long-term success of periimplantitis treatment
and the effectiveness of various therapeutic interventions. MATERIALS AND
METHODS: A total of 142 patients were referred to the Academy for Oral
Implantology in Vienna for the treatment of recurrent periimplantitis around
single-tooth implants. Of them, 72 patients (51%) were treated by laser
decontamination, 47 patients (33%) by implantoplasty surgery, and 23 patients
(16%) by a combination of both approaches. RESULTS: Overall success of
periimplantitis therapy was 89% after 9 years of follow-up, and it did not differ
significantly between female and male patients (P = 0.426). The number of implant
failures that could not be prevented by periimplantitis treatment was 6 after
laser decontamination (8%), 6 after implantoplasty surgery (13%), and 4 after a
combination of both therapies (17%). Implant loss occurred after 4.9 +/- 1.9
years of therapy, on average. No significant difference between the 3 treatment
groups could be observed (P = 0.393). CONCLUSION: The present results suggest
that success rates of periimplantitis therapy with either laser decontamination
or surgical implantoplasty are high. These success rates do not appear to be
associated with patient gender or treatment strategy.
PMID- 27504534
TI - The Effect of Platform Switching on Periimplant Crevicular Fluid Content During
Early Wound Healing.
AB - PURPOSE: The objective of this study was to investigate the soft tissue response
and periimplant crevicular fluid (PICF) content around platform-switched (PS) and
platform-matched (PM) implants during early healing. MATERIALS AND METHODS:
Nonsmokers treatment planned to receive a single implant in 2 quadrants were
recruited. Two-stage implant placement protocol with 1 PM and 1 PS implant was
implemented. Periimplant probing depths (PDs), modified sulcus bleeding index,
and plaque indices were recorded, and PICF was collected at 1, 2, 4, and 6 weeks
after abutment connection. RESULTS: PD readings were higher at week 1 than at
week 6 for both groups (P = 0.0005). PD was statistically deeper in PM than in PS
at week 1 (P = 0.03). There was a time-dependent decrease in total PICF volume
for both groups. This decrease was statistically significant for PS (P = 0.0005),
with no differences between the 2 groups at any time (P > 0.05). The decrease
observed in both PM and PS for PICF interleukin 6 and macrophage inflammatory
protein-1beta, and in PS for tumor necrosis factor-alpha (TNF-alpha) was
statistically significant (P <= 0.03). TNF-alpha was statistically higher in PS
than in PM at week 1 (P = 0.005). CONCLUSION: Within the limits of this study, it
seems that periimplant soft tissue response around PM and PS implants is mostly
similar during the early healing period.
PMID- 27504535
TI - Clinical and Microcomputed Topography Evaluation of the Concentrated Growth
Factors as a Sole Material in a Cystic Bony Defect in Alveolar Bone Followed by
Dental Implantation: A Case Report.
AB - Concentrated growth factors (CGFs) can be used to enhance wound healing. This
case report describes a short-term effect of CGF grafting followed by implant
placement in a cystic bony defect within the mandible. Healing conditions were
monitored by 2 implant-related surgeries, radiographs, and a microcomputed
topography examination. Continuous increase of radiopacity in radiographs was
noticed till 6 months after grafting. Bone core specimen was taken at 3.5 months
after grafting, and percent bone volume reached 32.7% analyzed by microcomputed
topography. In conclusion, the present case showed bone regeneration in the
cystic bony defect grafted by CGFs alone.
PMID- 27504536
TI - Alignment of Biological Apatite c-Axis Under Functional Loading: A Preliminary
Report.
AB - PURPOSE: To understand the bone modeling/remodeling process of functionally
loaded implants by observing the alignment of the biological apatite (BAp) c
axis. MATERIALS AND METHODS: Commercially available titanium implants with TiO2
grit-blasted surfaces were placed in the fourth premolar and the first molar of
the beagle dog and were functionally loaded with casted crowns and were compared
to the non-loaded controls. After being killed, the samples were subjected to
histological observation and to a microbeam x-ray diffraction (MUXRD) analysis
with a transmission optical system to evaluate the preferential BAp c-axis
alignment. RESULTS: The non-loaded group presented mostly nonoriented BAp c-axis
around the implant, whereas for the loaded group, preferential alignment of BAp c
axis was observed along the loading direction of the implant suggesting that the
Bap aligned itself based on the direction of the functional mechanical loading.
CONCLUSION: The MUXRD revealed that the c-axis orientation was perpendicular to
the implant thread working against the functional loaded direction, which may
contribute in designing an optimal implant macrogeometry.
PMID- 27504537
TI - Dihydrobenzofuran Neolignanamides: Laccase-Mediated Biomimetic Synthesis and
Antiproliferative Activity.
AB - The biomimetic synthesis of a small library of dihydrobenzofuran neolignanamides
(the natural trans-grossamide (4) and the related compounds 21-28) has been
carried out through an eco-friendly oxidative coupling reaction mediated by
Trametes versicolor laccase. These products, after complete spectroscopic
characterization, were evaluated for their antiproliferative activity against
Caco-2 (colon carcinoma), MCF-7 (mammary adenocarcinoma), and PC-3 (prostate
cancer) human cells, using an MTT bioassay. The racemic neolignamides (+/-)-21
and (+/-)-27, in being the most lipophilic in the series, were potently active,
with GI50 values comparable to or even lower than that of the positive control 5
FU. The racemates were resolved through chiral HPLC, and the pure enantiomers
were subjected to ECD measurements to establish their absolute configurations at
C-2 and C-3. All enantiomers showed potent antiproliferative activity, with, in
particular, a GI50 value of 1.1 MUM obtained for (2R,3R)-21. The effect of (+/-)
21 on the Caco-2 cell cycle was evaluated by flow cytometry, and it was
demonstrated that (+/-)-21 exerts its antiproliferative activity by inducing cell
cycle arrest and apoptosis.
PMID- 27504538
TI - Decomposition and Cell Failure Mechanisms in Lead Halide Perovskite Solar Cells.
AB - Perovskite solar cells have experienced a remarkably rapid rise in power
conversion efficiencies, with state-of-the-art devices now competing with
multicrystalline silicon and thin-film cadmium telluride in terms of efficiency.
Unfortunately, the lead halide perovskite absorbers suffer from a lack of
chemical stability and decompose in response to a variety of environmental
stimuli. In this Forum Article, we provide a brief overview of the decomposition
mechanisms in lead halide perovskite thin films, as well as the processes
contributing to cell failure in finished devices. We finish by briefly surveying
recent efforts to extend the device lifetime. Ultimately, if perovskite solar
cells can be made stable, they will be an exciting, highly complementary addition
to existing photovoltaic technologies.
PMID- 27504539
TI - Building the bacterial cell wall at the pole.
AB - Polar growth is the predominant mode of cell wall extension in the Actinobacteria
and the alphaproteobacterial clade Rhizobiales. The observation of polar
elongation in taxonomically diverse bacteria suggests that polar growth may have
evolved independently. Indeed, the regulatory mechanisms governing the assembly
of cell wall biosynthesis machinery at the pole are distinct in the
Actinobacteria and Rhizobiales. Here we highlight recent advances in our
understanding of polar growth mechanisms in bacteria, with an emphasis on
Streptomyces and Agrobacterium. This review illustrates that common themes are
emerging in the regulation of polar growth in diverse bacteria. Emerging themes
include the use of landmark proteins to direct growth to the pole and
coordination of polar growth with cell-cycle progression.
PMID- 27504540
TI - Cell biology of corn smut disease-Ustilago maydis as a model for biotrophic
interactions.
AB - Ustilago maydis is a well-established model system for biotrophic fungal plant
pathogens. The fungus has a dimorphic life cycle with a yeast-like saprophytic
phase switching to filamentous, pathogenic growth upon hyphal fusion. Due to its
highly differentiated development and the amenability for reverse-genetics U.
maydis provides a model system for both fungal cell biology as well as the study
of biotrophic plant interaction. The present article highlights key findings in
different aspects of cell biology on the corn smut disease and provides an
outlook on the most intriguing open questions.
PMID- 27504541
TI - New Oral Anticoagulants: Need and Challenges in a Developing Country.
PMID- 27504542
TI - Determination of Prevalence of Dental Erosion in 12 - 14 Years School Children
and Its Relationship with Dietary Habits.
AB - OBJECTIVE: To determine the frequency of dental erosion in 12-14 years school
children and its association with dietary habits. STUDY DESIGN: Observational
cross-sectional analytical study. PLACE AND DURATION OF STUDY: Fatima Jinnah
Dental College, Karachi, from January to June 2010. METHODOLOGY: School children
aged between 12 - 14 years were included in this study. Dental erosion was
detected by visual examination. Aself-developed questionnaire was used to assess
the dietary habits of children. Acidic diet was considered a diet that has an
acidic pH. The amount of consumption of acidic drinks and food per week was
categorized into low consumption (1 - 7 times / week) and medium consumption (8 -
21 times / week). Chi-square test was applied to see any statistical difference
between diet and tooth erosion at 95% CI. RESULTS: The results showed a high
frequency of (46%) dental erosion in children, which was significantly higher (p
< 0.001) in children with more acidic diet. CONCLUSION: This study highlights the
impact of dietary habits on the prevalence of dental erosion in children. Acidic
diets need to be controlled in frequency to prevent dental erosion.
PMID- 27504543
TI - Efficacy of Trichloro-Acetic Acid Peel Alone Versus Combined Topical Magnesium
Ascorbyl Phosphate for Epidermal Melasma.
AB - OBJECTIVE: To compare the efficacy in terms of reduction in melasma area and
severity index (MASI) score by more than 10 of a combination of 20% trichloro
acetic acid peel plus 5% topical magnesium ascorbyl phosphate versus 20%
trichloroacetic acid peel alone in the treatment of epidermal melasma. STUDY
DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Department of
Dermatology, Lady Reading Hospital (LRH), Peshawar, from May 2012 to May 2013.
METHODOLOGY: Patients aged 18 - 65 years, with Fitzpatrick skin type III-V were
divided into two equal groups having 74 patients each. Detailed history was taken
and Wood's lamp examination done to rule out mixed and dermal melasma. Melasma
area and severity index (MASI) score was calculated for every patient. Priming
was done for all patients with tretinoin cream applied once daily at night for 2
weeks, and to use a broad spectrum sun block cream before sun exposure. Patients
in group Awere subjected to combined treatment, i.e. trichloro-acetic acid peel
20% (weekly) plus magnesium ascorbyl phosphate cream (applied once daily), while
patients in group B were subjected to trichloro-acetic acid peel 20% (weekly)
alone. Treatment was continued for 6 weeks. After completion of treatment, MASI
score was recalculated. Proportion of patients with significant MASI score
reduction was compared using chi-square test with significance at p < 0.05.
RESULTS: Male and female patients were 11 (14.9%) and 63 (85.1%), respectively in
group A, whereas 13 (17.6%) and 61 (82.4%) in group B. The mean age in group Awas
30.28 +/-8.08 years, and 29.36 +/-6.84 years in group B. Significant MASI score
reduction in group Awas seen in 60 (81.1%) patients and in group B 49 (66.2%, p=
0.040). CONCLUSION: Combination of trichloro-acetic acid peel and topical
magnesium ascorbyl phosphate cream was significantly more effective than
trichloro-acetic acid peel alone in treatment of melasma.
PMID- 27504544
TI - Diagnostic Accuracy of Perfusion Computed Tomography in Cerebral Glioma Grading.
AB - OBJECTIVE: To determine the diagnostic accuracy of perfusion computed tomography
(PCT) in the grading of cerebral glioma. STUDY DESIGN: Cross-sectional analytical
study. PLACE AND DURATION OF STUDY: Department of Radiology, Allied Hospital,
Faisalabad, from January to June 2014. METHODOLOGY: All the patients with
untreated glioma had an initial non-contrast head CT and then PCT using 128
multidetector CTscanner. Perfusion maps of permeability surface (PS) and cerebral
blood volume (CBV) were generated and measured. As control, a second volume of
interest was placed in the contralateral healthy cortex. PCT parameters were
compared with World Health Organization (WHO) glioma grades. RESULTS: Fifty
patients of 30 - 70 years of age of both genders (mean 45.13 +/-5.54), 31 (62%)
males and 19 (38%) females were studied. These patients were classified as low
grade glioma group (22 patients) and high-grade glioma group (28 patients). PS
showed the sensitivity of 95.45%, specificity of 92.86% and diagnostic accuracy
of 94% in differentiating the low-grade and high-grade glioma by using a cut-off
value of 3.6 ml/100 g/minute. By using a cut-off value of CBV of 2.08 (ml/100 g)
among low-grade and high-grade glioma group, CBV showed the sensitivity of 77.3%,
specificity of 89.3%, and diagnostic accuracy of 84%. CONCLUSION: The derived
parameters (PS and CBV) correlate well with tumor histopathology, differentiating
low-grade from high-grade gliomas. PS showed better accuracy for glioma grading.
PMID- 27504545
TI - Frequency of Hepatic Hydrothorax and its Association with Child Pugh Class in
Liver Cirrhosis Patients.
AB - OBJECTIVE: To determine the frequency of hepatic hydrothorax and its association
with Child Pugh Class in patients with liver cirrhosis. STUDY DESIGN:
Descriptive, analytical study. PLACE AND DURATION OF STUDY: Jinnah Postgraduate
Medical Centre, Karachi, Medical Unit-III, (Ward- 7), from June 2012 to May 2013.
METHODOLOGY: All patients with established diagnosis of decompensated chronic
liver disease were included. Detailed history, thorough physical examination,
routine laboratory investigations, chest X-ray and abdominal ultrasound were
carried out in all patients to find out the presence of pleural effusion and
ascites, respectively. Fifty milliliters of pleural fluid was aspirated in all
patients with pleural effusion using the transthoracic approach, taking
ultrasound guidance, wherever required. Fluid was sent for microscopic,
biochemical, and microbial analysis. SBEM defined if pleural fluid with
polymorphonuclear (PMN) cell count > 500 cells/mm3 or positive culture with PMN
cell count > 250 cells/mm3 with exclusion of a parapneumonic effusion. RESULTS:
Two hundred and six patients met the inclusion criteria, with mean age of 41.25
+/-13.59 years. Among them, 149 (72.3%) were males and 57 (27.7%) females. Twenty
three (11.2%) had hydrothorax; right sided involvement was in 18 (78.3%)
subjects, 3 (13%) had left sided while bilateral pleural effusion was found in 2
(8.7%) cases. SBEM was found in 07 (30.43%) cases. Mean serum albumin 3.125 +/
0.71 gram/dl. There was association between serum albumin levels and hydrothorax.
Asignificant association of hydrothorax with Child Pugh scoring system (p=0.018),
but not with serum albumin (p=0.15). CONCLUSION: The frequency of hepatic
hydrothorax has a significant association with hepatic function as assessed by
Child Pugh scoring system, but not with serum albumin.
PMID- 27504546
TI - Immunohistochemical Expression of Epidermal Growth Factor Receptor and c-Kit in
Triple Negative Breast Cancer.
AB - OBJECTIVE: To determine the frequency of immunohistochemical expression of
epidermal growth factor receptor (EGFR) and c-KITin triple negative breast cancer
(TNBC). STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF
STUDY: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from January to
December 2014. METHODOLOGY: Fifty cases of triple negative breast cancer
diagnosed on immunohistochemistry were included in the study. Patients'gender and
age were noted. Immunohistochemistry for EGFR and c-KITwere applied and the
results were recorded. The data were analyzed by using computer software
programme SPSS version 19. Descriptive statistics, frequencies and percentages
were calculated. RESULTS: Out of 50 patients of TNBC, all patients were females.
The ages of the patients ranged between 30 and 80 years with an average age of
48.9 years and standard deviation of +/-10.0. Out of 50 cases, 29 cases (58%)
were positive for EGFR while 15 cases (30%) were positive for c-KIT. Thirteen
cases (26%) were positive for both EGFR and c-KIT. Nineteen cases (38%) were
negative for both EGFR and c-KIT. CONCLUSION: EGFR expression was observed in 58%
and c-KITexpression was seen in 30% of the cases. The results of EGFR expression
are almost similar while those of c-KIT are different from international studies
which suggest immunohistochemical differences between the studied populations.
PMID- 27504547
TI - Peer-Assisted Learning: Who Should Be the Tutor, Fellow Student or Senior
Resident?
AB - OBJECTIVE: To compare student-tutor guided peer-assisted learning (STPAL) and
resident-tutor guided peer-assisted learning (RTPAL) for its impact on
performance of students in summative assessment. STUDY DESIGN: Quasi-experimental
study. PLACE AND DURATION OF STUDY: Gujranwala Medical College, from February to
September 2015. METHODOLOGY: Four batches each of final year MBBS students were
first trained for clinical skills by resident-tutors for 2 weeks and had a pre
test. Two students with highest marks were selected as student-tutors. Half of
the batch had a further 2 weeks skill training by the student-tutors while other
half by resident-tutor, post-test was carried out after 2 weeks. Improvement in
scores was compared between STPAL and RTPAL groups, using unpaired student t
test. The batch underwent same intervention for the next month with cross-over of
STPAL and RTPAL groups. RESULTS: Study population was 152 out of expected 188 as
batch D underwent the study only once and 13 students were either absent or had
decline in scores, so were excluded. Among 74 (48.68%) STPALand 78 (51.23%) RTPAL
students, median improvement in scores was 8 for STPAL group as compared to 7 for
RTPALgroup; the difference was not statistically significant (p= 0.61).
CONCLUSION: Student-tutor guided peer-assisted learning is as effective as
resident-tutor peer assisted learning in improving performance of the students.
PMID- 27504548
TI - ICU Pathogens: A Continuous Challenge.
AB - OBJECTIVE: To determine the frequency and antibiogram of pathogens in an
intensive care unit (ICU). STUDY DESIGN: Cross-sectional, observational study.
PLACE AND DURATION OF STUDY: Department of Microbiology, Army Medical College,
National University of Science and Technology, Islamabad, from January 2013 to
January 2014. METHODOLOGY: Clinical samples, received from patients admitted in
ICU, were inoculated on various medias like blood agar, chocolate agar, MacConkey
agar and urine samples on CLED. These were then incubated at 37 degrees C for 24
hours. Isolates were identified by colony morphology, Gram reaction, catalase
test, oxidase test. Species identification in case of Gram Negative Rods was done
by using API 20E (BioMerieux). Antibiotic susceptibility was done by using
modified KirbyBauer disc diffusion technique. Bacterial isolates were prepared
and inoculated on Mueller-Hinton agar plates followed by application of various
antibiotic disc (Oxoid, UK) as per manufacturer's instructions. The plates were
then incubated at 37 degrees C aerobically for 18 - 24 hours. Zone diameters were
measured and interpreted as sensitive and resistant, according to Clinical and
Laboratory Standards Institute (CLSI) guidelines. RESULTS: Out of the 367
positive cultures, 116 (31.08%) were Acinetobacter baumanniisusceptible to
minocycline and tigecycline followed by Klebsiella pneumoniae (n=71, 16%)
susceptible to tigecycline and meropenem. Others were Pseudomonas aeruginosa,
Escherichia coli,Coagulase Negative Staphylococcus, Staphylococcus aureus,
Enterococcus spp., Streptococcus spp., Klebsiella oxytoca, Stenotrophomonas
maltophilia,and Candida spp. CONCLUSION: Acinetobacter baumanniiwas the most
frequently isolated pathogen. Most of the cultures yielding pathogens were from
respiratory tract samples. Gram negative isolates were multidrug resistant but
most were tigecycline and susceptible to meropenem.
PMID- 27504549
TI - Species Identification and Antibiotic Susceptibilities of Coagulase- Negative
Staphylococci Isolated from Urinary Tract Infection Specimens.
AB - OBJECTIVE: To determine the incidence of Coagulase- negative S. aureusin urinary
tract infections and sensitivities of these isolates to antimicrobial agents.
STUDY DESIGN: Cohort study. PLACE AND DURATION OF STUDY: Dr. Essa Laboratory and
Immunology and Infectious Disease Research Laboratory (IIDRL), Microbiology
Department, University of Karachi, from January 2009 to January 2010.
METHODOLOGY: Urine specimens, suggestive of urinary tract infection (UTI), were
identified. Speciation of isolates was done using API-20 Staph.system. Screening
of extracellular products was done using SDS-PAGE electrophoresis and Hemolysin
on blood-agar plates. Minimum inhibitory concentration (MICs) of antibiotics was
estimated by microtiter well plate method. Frequency and percentages were
determined and chi-square test was used for comparing proportions with
significance at p < 0.05. RESULTS: Coagulase - negative S. aureus(CONS) were the
cause of urinary tract infection in 56 out of 1866 outpatient (3%) and 164 of
1261 inpatient (13%), urinary tract infections (p < 0.001). Two hundred and
twenty CONS isolates were identified. The most common CONS identified was S.
saprophyticus (31%, 68 strains). The relative frequency of Coagulase - negative
S. aureuswas 6% (13 strains). All isolates were sensitive to Vancomycin and
Linezolid. Resistance was 69% to Ampicillin, 53% to Methicillin, and 37.5% to
Ciprofloxacin. CONCLUSION: CONS are a potential uropathogens, with capability of
slime production and resistance to common empirical prescriptions. This also
warrants formulation of an appropriate antibiotic policy that covers CONS.
PMID- 27504550
TI - Pattern of Polymicrobial Isolates and Antimicrobial Susceptibility from Blood.
AB - OBJECTIVE: To determine the pattern of polymicrobial isolates in blood cultures
and antimicrobial susceptibility in a tertiary care hospital of Karachi. STUDY
DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Sindh Institute of
Urology and Transplantation (SIUT), Karachi, Pakistan, from September to November
2014. METHODOLOGY: Blood culture samples were received from patients, which were
processed by BACTEC 9240 system (Becton Dickinson). All positive blood samples
were further analyzed. Susceptibility to antimicrobial agents was determined
according to the Clinical and Laboratory Standards Institute (CLSI) criteria of
the year. Identification of growth was based on Gram staining, colony morphology
and appropriate biochemical tests. Antibiotic susceptibility was done as per
Clinical and Laboratory Standards Institute (CLSI) recommendations. RESULTS: Out
of the 7251 samples submitted, 2931 (40.42%) were positive for growth, 2389
(81.5%) samples were monomicrobial, whereas 542 (18.5%) samples were
polymicrobial. Among the polymicrobial isolates, 468 (86.34%) blood culture
samples yielded two, 66 (12.17%) yielded three, and 8 (1.47%) yielded four
organisms. Gram positive isolates were 281 (51.84%) and Gram negative were 261
(48.15%). The most frequent isolates in polymicrobial blood stream infection were
Acinetobacterspp. (51/542, 9.4%) and Coagulase negative Staphylococcus(84/542,
15.5%), respectively. Staphylococcus aureus isolates, which were resistant to
Methicillin, accounted for 24.65%. Third generation Cephalosporins resistance in
Klebsiella spp. and Eschericia (E.) coli was found to be 63.6% and 58%,
respectively. Carbapenem resistance was seen in 5.9% of Pseudomonas aeruginosaand
17.6% Acinetobacter spp. CONCLUSION: Gram positive bacteria were more commonly
involved in polymicrobial blood stream infections with Coagulase negative
Staphylococcusbeing the most common Gram positive isolate. Methicillin-resistant
Staphylococcus aureusaccounted for one-fourth of isolates. Higher resistance to
third generation Cephalosporins was seen in Klebsiella spp. and E.coli isolates.
Resistance of Pseudomonas aeruginosaand Acinetobacter species to Carbapenems was
found out to be on the lower side.
PMID- 27504551
TI - Comparison of Efficacy of Tacrolimus Versus Cyclosporine in Childhood Steroid
Resistant Nephrotic Syndrome.
AB - OBJECTIVE: To compare the efficacy of tacrolimus versus cyclosporine (Calcineurin
Inhibitors) in the management of childhood steroid-resistant nephritic syndrome
(SRNS). STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY:
Department of Paediatric Nephrology at The Children's Hospital and Institute of
Child Health, Lahore, from August 2014 to September 2015. METHODOLOGY: Patients
of either gender aged 1 - 12 years, with the diagnosis of mesangioproliferative
glomerulonephritis (MesangioPGN), focal segmental glomerulosclerosis (FSGS) or
minimal-change disease (MCD) were included. Patients were assigned into two
groups, one given tacrolimus in dose of 0.1 - 0.2 mg/kg/day in two divided doses,
and other given cyclosporine in dose of 150 - 200 mg/m2/day in two divided doses
along with oral steroids 30 mg/m2/day in divided doses, followed by alternate day
with tapering dosage. Trough drug levels were done with dose adjustment
accordingly. Patients were monitored and followed for the response to treatment
and adverse effects of these two calcineurin inhibitors. RESULTS: Atotal of 84
patients, 58% males and 42% females, were included in the study. The age ranged
from 1.25 to 12 years. The most common histopathological diagnosis was
MesangioPGN (69.04%), FSGS (21.4%), and MCD (9.52%). Complete response was seen
in 80.95% and 97.6% patients treated with cyclosporine and tacrolimus,
respectively. Partial response was in 19.05% patients treated with cyclosporine
and 2.4% in patients with tacrolimus. The most common adverse effect with
cyclosporine and tacrolimus was hypertrichosis in 80.95% and 2.38%, hypertension
16.66% and 11.9% respectively while gum hypertrophy with cyclosporine was seen in
26.19% patients. CONCLUSION: Tacrolimus was more efficacious than cyclosporine in
achieving remission in childhood SRNS with insignificant adverse effects.
PMID- 27504552
TI - Effects of Cobalt Nitrate on Histopathological and Morphometric Changes in Rat
Femoral Artery Vasospasm Model.
AB - OBJECTIVE: To determine the effects of cobalt nitrate on the arterial wall in a
rat femoral artery vasospasm model. STUDY DESIGN: Experimental study. PLACE AND
DURATION OF STUDY: Faculty of Medicine, Istanbul University, between November
2009 and September 2010. METHODOLOGY: Twenty-four rats were separated into three
groups named group 1 (n=8, sham-control); group 2 (n=8, vasospasm), and group 3
(n=8, vasospasm + cobalt nitrate treated). Group 3 rats were subjected to
intraperitoneal administration of 0.1 mg/kg/day cobalt nitrate for 7 days,
followed by histological and morphometric analyses. ANOVAand post hoc analyses
were carried out. RESULTS: The mean vascular wall thickness of the group 1, 2 and
3 rats was found to be 133 +/-13, 210 +/-15 and 160 +/-11 micron, respectively.
The mean vascular lumen diameter of the group 1, 2 and 3 rats was 698 +/-20, 240
+/-15 and 540 +/-22 micron, respectively. Arteries in the group 3 had thin smooth
endothelium, thin mildly folded internal elastic lamina, and concentric smooth
muscle cells. The mean vascular lumen diameter of the group 3 rats showed a
significant decrease compared to the group 2 rats. CONCLUSION: Cobalt nitrate may
potentially serve as an agent in preventing cerebral vasospasm after a
hemorrhagic episode.
PMID- 27504553
TI - Retinal Thickness and Visual Acuity in Diabetic Macular Edema: An Optical
Coherence Tomography-Based Study.
AB - OBJECTIVE: To determine the relationship between foveal (retinal) thickness and
visual acuity in diabetic macular edema through optical coherence tomography
(OCT) mapping software. STUDY DESIGN: Cross-sectional descriptive study. PLACE
AND DURATION OF STUDY: The Retina Clinic of Al-Shifa Trust Eye Hospital,
Rawalpindi, from August 2011 to August 2012. METHODOLOGY: Eighty eyes of 68
patients with clinical diagnosis of diabetic macular edema, based on complete
ophthalmic examination, were enrolled. The best-corrected visual acuity was
recorded on logMar scale. OCTimaging was performed through dilated pupil by
experienced operator. Foveal thickness was determined. OCTparameters of macular
thickness were analysed with baseline variables including age, duration since
diagnosed with diabetes, and visual acuity. RESULTS: The mean visual acuity was
0.81 (0.2 - 1.8) logMar units. The average foveal thickness was 395.09 +/-142.26
(183 - 825 um). There was moderate correlation between foveal thickness and
visual acuity (rs= 0.574, p < 0.001), absent in those who had visual acuity worse
than 1 logMar. There was a weak positive association between foveal thickness and
the duration of diabetes (rs=0.249, p < 0.05). There was, however, no correlation
between foveal thickness and age (rs= 0.012, p=0.919). CONCLUSION: There is a
moderate correlation between visual acuity and degree of foveal thickening in
diabetic macular edema, hence two cannot be used interchangeably in clinical
practice.
PMID- 27504554
TI - Arterial and Ventricular Elastance and Ventriculo-arterial Coupling in Asthmatic
Children.
AB - OBJECTIVE: To compare arterial and ventricular end-systolic elastance and
ventriculo-arterial coupling between asthma and healthy children and correlate
these all three parameters with pulmonary function tests in subjects with asthma.
STUDY DESIGN: Across-sectional analytical study. PLACE AND DURATION OF STUDY:
Department of Pediatrics, Bozok University Medical Faculty,Yozgat, Turkey, from
January 2012 to November 2014. METHODOLOGY: Transthoracic and Doppler
echocardiography and pulmonary function tests in patients with asthma aged 7 - 12
years and control subjects. Forty stable asthma patients on prophylactic inhaled
corticosteroids and 97 healthy subjects were investigated. Both groups were
matched for age, gender, blood pressure, heart rate, body surface area,
echocardiographic parameters and pulmonary function tests. RESULTS: There was no
difference regarding left ventricular elastance at end-systole derived by single
beat/body surface area (Ees(sb)/BSA) between asthmatic patients and healthy
children (2.59 +/-1.29 mmHg/ml/m2, 2.43 +/-1.28 mmHg/ml/m2 respectively,
p=0.504), arterial elastance/BSA(Ea/BSA) (2.10 +/-0.97, 1.75 +/-0.89
respectively, p=0.041), and ventriculoarterial coupling (VAC) (0.83 +/-0.13, 0.74
+/-0.13, respectively, p < 0.001) were higher in asthmatic group than controls.
There was no correlation between Ea, Ees (sb), VAC and pulmonary function tests.
CONCLUSION: Arterial elastance increase and stiffness decrease in asthmatic
patients. This may be due to using prophylactic inhaled corticosteroids. Using
inhaled corticosteroids have protective effects against atherosclerosis. As a
result of this higher arterial elastance, asthmatic children had higher VAC
resulting in less efficient cardiovascular function.
PMID- 27504555
TI - Childhood Trauma and Alexithymia in Patients with Conversion Disorder.
AB - OBJECTIVE: To determine the relationship between childhood trauma (physical,
sexual, emotional abuse and neglect) and alexithymia in patients with conversion
disorder, and to identify it as a predictor of alexithymia in conversion
disorder. STUDY DESIGN: An analytical study. PLACE AND DURATION OF STUDY:
Multiple public sector hospitals in Lahore, from September 2012 to July 2013.
METHODOLOGY: Eighty women with conversion disorder were recruited on the basis of
DSM IV-TR diagnostic criteria checklist to screen conversion disorder. Childhood
abuse interview to measure childhood trauma and Bermond Vorst Alexithymia
Questionnaire, DSM-IV TR Dianostic Criteria Checklist, and Childhood Abuse
Interview to assess alexithymia were used, respectively. RESULTS: The mean age of
the sample was 18 +/-2.2 years. Thirty-six cases had a history of childhood
trauma, physical abuse was the most reported trauma (f = 19, 23.8%) in their
childhood. Patients with conversion disorder has a significant association with
alexithymia (p < 0.05). Multiple regression analysis showed that childhood sexual
abuse could predict alexithymia (F= 7.05, p < 0.05). Among the alexithymia
domain, childhood physical abuse significantly predicted the difficulty in
verbalizing emotions among the abused patients (F= 6.40, p < 0.05). CONCLUSION:
The study highlighted childhood abuse and emotional pent up as an etiological
factor of conversion disorder. Strategies should be devised to reduce this
disorder among women in Pakistani society.
PMID- 27504556
TI - AParadigm Shift: The New Novel Oral Anticoagulation Agents.
AB - Atrial fibrillation (AF) is the most common arrhythmia and represents one-third
of the arrhythmia-related hospital admissions in the developed countries. Embolic
strokes associated with AF are more severe and disabling. Thromboembolic stroke
prevention is a major goal in treatment of AF and Warfarin has successfully
served this purpose for many years. Drug-drug interaction and regular monitoring
with Warfarin pose a significant challenge where health care system has limited
resources; and lack of a well-structured health system, hinders regular
International Normalized Ratio (INR) monitoring. Novel oral anticoagulants
(NOACs) have opened up a new exciting chapter in the field of anticoagulation in
non-valvular atrial fibrillation (NVAF). This review discussed the landmark
trials that led to the development of NOACs and explored the potentials of these
new agents with simultaneous comparison of Warfarin.
PMID- 27504557
TI - Major Lower Limb Amputations: Experience of a Tertiary Care Hospital in Sri
Lanka.
AB - OBJECTIVE: To determine the epidemiology and conditions frequently seen in major
lower extremity amputation. STUDY DESIGN: Observational study. PLACE AND DURATION
OF STUDY: Teaching Hospital Karapitiya, Sri Lanka, from October 2013 to September
2014. METHODOLOGY: Major lower limb amputations were identified according to ICD
10 criteria. Data was retrospectively collected. Type of the amputation,
indication for the amputation, gender and age of the patients, and mortality were
noted. RESULTS: Eighty-five cases of major lower limb amputations were analyzed,
including 43 above-knee amputations, 40 below-knee amputations, and 2 through
knee amputations. Most of the patients were in their 7th (38.8%, n=33) and the
8th (21%, n=18) decade of life. Female to male ratio was 1:1.7. Indications of
lower extremity amputation were diabetic foot ulcer (37.6%, n=32), peripheral
vascular disease (31.7%, n=27), followed by trauma (n=6), acute limb ischemia and
infections (n=5 each), chronic osteomyelitis (n=4), tumors (n=3), elephantiasis,
pressure sore and chronic wound (n=1 each). Overall diabetes frequency was 52.9%
(n=45). In-hospital mortality rate was 9.4%. Main cause of deaths was septicemia.
CONCLUSION: In the study population, major lower limb amputations were more
common in males compared to females, with highest incidence in the 7th and 8th
decades. Diabetes mellitus contributed to more than 50% of amputations directly
or indirectly, and septicemia was responsible for the most mortality.
PMID- 27504558
TI - Spindle Cell Sarcoma Presenting as Pancoast Syndrome.
AB - This report describes a patient who presented with pancoast syndrome, secondary
to spindle cell sarcoma of the lung. A 56-year man presented with dyspnea,
engorged neck veins and bilateral upper limb pitting edema. The patient also had
ptosis and miosis in the right eye. Right ulnar nerve palsy with atrophy of hand
muscles was seen. His chest X-ray showed bilateral pleural effusion with an
opacity involving the apex of the right lung along with mediastinal widening.
Echocardiography revealed a pericardial effusion which was drained. The patient's
CTscan of chest strongly suspected a malignant mass in right upper lobe with
extensive mediastinal lymphadenopathy, pleural metastases and pericardial
involvement. He was started on oxygen inhalation, dexamethasone, and clopidogrel.
Bronchoscopic biopsy confirmed the diagnosis of spindle cell sarcoma. Meanwhile,
he was advised radiotherapy. The tumour was not amenable to surgery. Spindle cell
sarcoma is a rare connective tissue tumor that replicates rapidly. To the best of
the authors' knowledge, it is hereby reported the first case of spindle cell
sarcoma of the lung presenting as Pancoast syndrome.
PMID- 27504559
TI - Pneumocephalus in Child Following Bilateral Otomastoiditis and Nasal Septum
Infection.
AB - Pneumocephalus is collection of gas or air within the cranial cavity, commonly
associated with trauma, cranial surgery, air embolism, open meningomyelocele; and
rarely as a result of central nervous system infections. Asymptomatic
pneumocephalus usually recovers spontaneously within few days. Untreated
pneumocephalus can progress to tension pneumocephalus, manifesting as severe
headache, dizziness, cranial nerve palsy, mental changes, seizure and
disorientation. Herein, we report a rare case of pneumocephalus in a 9-month
infant with subdural effusion following infection of nasal septum and
otomastoiditis. There was no sign of meningitis but CThead showed communication
of intracranial dura mater across widened foramen caecum with pre-nasal space,
and bilateral otomastoiditis with erosion of anterior and lateral wall of right
mastoid bone. The patient was treated successfully and discharged without
sequelae.
PMID- 27504560
TI - Nd YAG Laser Embolysis in a Young Woman with Hemiretinal Artery Occlusion.
AB - Retinal artery occlusion is an uncommon condition but can lead to grave
consequences if not managed in time. Elderly population with other comorbid
conditions like hypertension, ischemic heart disease, hyperlipidemia and stroke
are commonly affected. However, this condition may affect younger population with
entirely different systemic associations. Thromboembolism, which usually takes
place secondary to cardiac emboli or hypercoagulable states cause retinal artery
occlusion in young population. A24-year lady presented with a short history of
unilateral altitudinal visual loss. On examination, she was found to have
hemiretinal artery occlusion. Ocular massage, anterior chamber paracentesis was
performed initially, followed by Nd YAG laser embolysis, which led to successful
restoration of retinal circulation and significant improvement in visual field
loss. Detailed evaluation and systemic investigations were carried out to
identify the underlying cause, but no systemic association could be found.
PMID- 27504561
TI - Angioleiomyoma of Gingiva Masquerading as Pyogenic Granuloma.
AB - Leiomyomas are benign soft tissue neoplasms that arise from smooth muscles. Three
distinctive patterns of leiomyoma have been described as piloleiomyomas,
angioleiomyomas and genital leiomyomas. Here in, we report the case of 39-year
male with chief complain of growth on his lower left front region of the jaw. On
the basis of clinical examination, it was provisionally diagnosed as pyogenic
granuloma; however, histopathological examination made to the final diagnosis of
angioleiomyoma. Excision led to uneventful recovery.
PMID- 27504562
TI - Efficacy of Ganglioside GM1 in the Treatment of Postherpetic Neuralgia.
AB - Postherpetic neuralgia (PHN) is a commonest and difficult-to-manage complication
of Herpes zoster. This comparative study included 140 cases of PHN admitted in
the department of dermatology in Renmin Hospital of Wuhan University, Wuhan,
China, from March 2014 to February 2015, divided into a control and a study
group. In addition to the combination of antiviral, analgesic, and neurotrophic
agents given to the control group, additional ganglioside GM1 was given to
patients in the study group. Pain assessment was performed at the time of
admission, and then on the third, seventh and tenth day of treatment, on both
groups, using a 10 cm visual analogue scale (VAS). There was a significant
statistical difference between the pain VAS score of the two groups, on the
seventh day (3.73 +/-1.66 vs. 3.03 +/-1.86, p=0.024) and on the tenth day (3.25
+/-1.78 vs. 2.20 +/-1.59, p=0.006) of treatment. The number of patients who have
good /and complete response (37.5%) were largely higher in the study group than
those in the control group (15%, p < 0.05). This finding demonstrates that the
administration of ganglioside GM1 may potentially serve as a neoadjuvant therapy
to reduce the severity and duration of pain in PHN patients.
PMID- 27504563
TI - Awareness Regarding Application of Endotracheal Tube (ETT) Cuff Pressure
Measuring Gauge in Anesthesia Practice; ACritical Step to Avoid Postintubation
Tracheal Stenosis in Critically ill Patients on Prolonged Mechanical Ventilator.
PMID- 27504564
TI - A Proposed Classification to Identify the Oral Manifestations of Genodermatoses.
PMID- 27504565
TI - Intraosseous Vascular Tumor of Mandible.
PMID- 27504566
TI - Percutaneous Endoscopic Lumbar Discectomy for Cauda Equina Syndrome.
PMID- 27504567
TI - Testicular Preserving Surgery: AJudicious Approach for Benign Testicular Lesion.
PMID- 27504568
TI - Gold Medal Award for Life Achievement in the Application of Psychology: David W.
Johnson.
AB - The American Psychological Foundation (APF) Gold Medal Awards recognize
distinguished and enduring records of accomplishment in four areas of psychology.
The 2016 recipient of Gold Medal Award for Life Achievement in the Application of
Psychology is David W. Johnson. Dorothy W. Cantor, president of the APF, will
present the APF Gold Medal Awards at the 124th Annual Convention of the American
Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF
Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice
president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer;
Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar;
Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence
M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw,
APA Board of Directors liaisons. (PsycINFO Database Record
PMID- 27504569
TI - Gold Medal Award for Life Achievement in the Practice of Psychology: Sandra L.
Shullman.
AB - The American Psychological Foundation (APF) Gold Medal Awards recognize
distinguished and enduring records of accomplishment in four areas of psychology.
The 2016 recipient of Gold Medal Award for Life Achievement in the Practice of
Psychology is Sandra L. Shullman. Dorothy W. Cantor, president of the APF, will
present the APF Gold Medal Awards at the 124th Annual Convention of the American
Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF
Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice
president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer;
Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar;
Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence
M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw,
APA Board of Directors liaisons. (PsycINFO Database Record
PMID- 27504570
TI - Gold Medal Award for Life Achievement in Psychology in the Public Interest:
Beatrice A. Wright.
AB - The American Psychological Foundation (APF) Gold Medal Awards recognize
distinguished and enduring records of accomplishment in 4 areas of psychology.
The 2016 recipient of Gold Medal Award for Life Achievement in Psychology in the
Public Interest is Beatrice A. Wright. Dorothy W. Cantor, president of the APF,
will present the APF Gold Medal Awards at the 124th Annual Convention of the
American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the
2016 APF Board of Trustees are: Dorothy W. Cantor, president; David H. Barlow,
vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer;
Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar;
Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence
M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw,
APA Board of Directors liaisons. (PsycINFO Database Record
PMID- 27504571
TI - Gold Medal Award for Life Achievement in the Science of Psychology: Richard E.
Nisbett.
AB - The American Psychological Foundation (APF) Gold Medal Awards recognize
distinguished and enduring records of accomplishment in four areas of psychology.
The 2016 recipient of Gold Medal Award for Life Achievement in the Science of
Psychology is Richard E. Nisbett. Dorothy W. Cantor, president of the APF, will
present the APF Gold Medal Awards at the 124th Annual Convention of the American
Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF
Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice
president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer;
Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar;
Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence
M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw,
APA Board of Directors liaisons. (PsycINFO Database Record
PMID- 27504572
TI - Charles L. Brewer Award for Distinguished Teaching of Psychology: Sue Frantz.
AB - The American Psychological Foundation (APF) Charles L. Brewer Distinguished
Teaching of Psychology Award recognizes an outstanding career contribution to the
teaching of psychology. The 2016 recipient of the Distinguished Teaching Award is
Sue Frantz. Dorothy W. Cantor, president of the APF, will present the
Distinguished Teaching Award at the 124th Annual Convention of the American
Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF
Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice
president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer;
Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar;
Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence
M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw,
APA Board of Directors liaisons. (PsycINFO Database Record
PMID- 27504573
TI - Proceedings of the American Psychological Association, Incorporated, for the
legislative year 2015: Minutes of the Annual Meeting of the Council of
Representatives February 20-22, 2015, Washington, DC, and August 5 and August 7,
2015, Washington, DC, and minutes of the February, June, August, and December
2015 meetings of the Board of Directors.
AB - This article provides the minutes of the Annual Meeting of the Council of
Representatives February 20-22, 2015, Washington, DC, and August 5 and August 7,
2015, Washington, DC, and minutes of the February, June, August, and December
2015 meetings of the Board of Directors. These minutes are the official record of
the actions of the Association taken during the year by both the Board of
Directors (the Board) and the Council of Representatives (Council). They are
arranged in topical rather than chronological order, and subheadings are used
when appropriate. (PsycINFO Database Record
PMID- 27504574
TI - Responding to change in a challenging climate: 2015 five-year report of the
Policy and Planning Board.
AB - The American Psychological Association (APA) Bylaws Article XI.7
(http://www.apa.org/about/governance/bylaws/article-11.aspx) requires that the
Policy and Planning Board report annually by publication to the membership and
review the structure and function of the association as a whole every fifth year.
This report details the board's 5-year review, including APA's challenges and
achievements from 2011 through 2015 within the context of broader social and
environmental changes. Recommended priorities for future change are offered.
(PsycINFO Database Record
PMID- 27504575
TI - Report of the Ethics Committee, 2015.
AB - The Report of the Ethics Committee, 2015, provides information on activities of
the Ethics Committee and Ethics Office during that year. In 2015, the Ethics
Office and Committee continued their work of adjudication, ethics education, and
ethics consultations. The Ethics Committee adopted minor changes to its "Rules
and Procedures" to increase the efficiency of the adjudication process. These
changes were approved by the APA Board of Directors to become effective on March
1, 2016. The Independent Review Report by David H. Hoffman was released in July.
The ethics office director also departed in July, and an interim ethics director
was appointed. The process for establishing a Commission on Ethics Processes was
also begun. The Commission has the charge of evaluating and recommending changes
to the American Psychological Association's current ethics program. Data for
adjudication processing in 2015 as well as comparisons to the previous 4 years
are provided. (PsycINFO Database Record
PMID- 27504576
TI - Summary Report of Journal Operations, 2015.
AB - Provides a summary report of Journal Operations. This summary is compiled from
the 2015 annual reports of the Council of Editors and from Central Office
records. (PsycINFO Database Record
PMID- 27504578
TI - Supplement to listing of accredited doctoral, internship, and postdoctoral
training programs in professional psychology.
AB - The Commission on Accreditation has provided a list announcing the following
status changes for Accredited doctoral (clinical, counseling, school, or a
combination thereof and developed practice area), doctoral internship, and
postdoctoral residency programs in professional psychology as of April 1, 2016.
(PsycINFO Database Record
PMID- 27504579
TI - Richard I. Evans (1922-2015).
AB - Presents an obituary for Richard I. Evans, who passed away on April 20, 2015, in
Houston, Texas, at the age of 92. Evans was a noted social and health
psychologist. He was one of the founding members of APA's division of Health
Psychology and served a term as president of the division. He had a major impact
on the history of psychology and media psychology, and was a central figure in
the development of the fields of health psychology and behavioral medicine.
(PsycINFO Database Record
PMID- 27504580
TI - Richard Michael Suzman (1942-2015).
AB - Presents an obituary for Richard Michael Suzman, who died on April 16, 2015.
Suzman was trained as a sociologist and anthropologist, but he was attracted to
the approaches of demography and economics. He came to know a great deal about
diverse fields of science, including health, physiology, psychology, genetics,
and economics. He was a scientific leader who was on a quest to develop new
transdisciplinary fields and to mobilize the best scientists to work in them.
Suzman's passion for transdisciplinary science was fully expressed in his
greatest achievement: the famous Health and Retirement Survey (HRS), which he
initiated in 1988 and continued to guide and inspire. (PsycINFO Database Record
PMID- 27504581
TI - Julian Meltzoff (1921-2015).
AB - Presents an obituary for Julian Meltzoff, who died on December 22, 2015, in his
La Jolla, California home. Meltzoff was a major architect of modern clinical
psychology. His innovative contributions in the arena of human service delivery,
his empirical evaluations of the efficacy of psychotherapy, and his creative
strategy for training clinical psychologists were truly ground breaking.
(PsycINFO Database Record
PMID- 27504582
TI - Judy Estes Hall (1940-2015).
AB - Presents an obituary for Judy Estes Hall, who passed away on November 24, 2015.
Hall served as the Executive Officer of the National Register of Health Service
Psychologists until her retirement in 2013. She is a recognized expert in the
development of education and training standards for the profession of psychology,
she also made significant contributions in the field of international psychology,
where she was a renowned expert in cross-national credentialing and an advocate
for commonality in licensing standards. She was the coauthor of one edited volume
and author of more than 60 journal articles, book chapters, and professional
publications. A passionate advocate for the advancement of women in psychology, a
devoted mother and grandmother, a connoisseur of wine and international traveler
extraordinaire, she touched the personal and professional lives of many.
(PsycINFO Database Record
PMID- 27504583
TI - 2015 Annual Report of the American Psychological Association.
AB - Presents the 2015 Annual Report of the American Psychological Association. In his
introduction, President Barry Anton describes how 2015 was among APA's most
challenging. Although 2015 ushered in an era of greater transparency within the
association and enhanced communications to members and the public, it also
required painful self-reflection stemming from the revelations of an independent
review by an outside law firm. The review examined the question of whether APA
played any role related to the Bush administration's use of abusive interrogation
techniques during the war on terror. Anton's introduction also discusses (1) the
APA convention, (2) representing APA at a White House meeting with health care
providers and insurance companies, (3) APA's effort to increase the number of APA
accredited internships, (4) international activities, and (5) the global summit
on psychology and integrated care. (PsycINFO Database Record
PMID- 27504584
TI - High-Resolution Tracking Asymmetric Lithium Insertion and Extraction and Local
Structure Ordering in SnS2.
AB - In the rechargeable lithium ion batteries, the rate capability and energy
efficiency are largely governed by the lithium ion transport dynamics and phase
transition pathways in electrodes. Real-time and atomic-scale tracking of fully
reversible lithium insertion and extraction processes in electrodes, which would
ultimately lead to mechanistic understanding of how the electrodes function and
why they fail, is highly desirable but very challenging. Here, we track lithium
insertion and extraction in the van der Waals interactions dominated SnS2 by in
situ high-resolution TEM method. We find that the lithium insertion occurs via a
fast two-phase reaction to form expanded and defective LiSnS2, while the lithium
extraction initially involves heterogeneous nucleation of intermediate
superstructure Li0.5SnS2 domains with a 1-4 nm size. Density functional theory
calculations indicate that the Li0.5SnS2 is kinetically favored and structurally
stable. The asymmetric reaction pathways may supply enlightening insights into
the mechanistic understanding of the underlying electrochemistry in the layered
electrode materials and also suggest possible alternatives to the accepted
explanation of the origins of voltage hysteresis in the intercalation electrode
materials.
PMID- 27504585
TI - The Science of Herbal Galactogogues.
PMID- 27504586
TI - The prevalence of hepatitis B infection in central China: An adult population
based serological survey of a large sample size.
AB - The objective of this study was to determine the prevalence of serum HBsAg among
adults in Henan province, China. A provincial serosurvey of people aged 18-74
years was conducted and individuals for analysis were selected using a multistage
stratified random cluster sampling method. A 5-ml serum sample from each person
was collected and the serum was tested for the presence of HBsAg, HBcAb, HBsAb,
HBeAg, and HBeAb by ELISA. Multivariate analysis was used to identify factors
associated with the prevalence of HBsAg. A total of 16,685 residents, aged 18-74
years who resided in 60 communities or villages in Henan, China were surveyed.
Among the eligible study population, 642 HBsAg positive cases (3.7%) were found.
The prevalence increased steadily from 3.1% among population aged 18-35 years
old, to 5.1% among population aged 55-74 years. Accordingly, HBsAb declined
steadily from 53.4% to 24.7%. Six hundred and forty-two positive HBsAg blood
samples were screened for the HBeAg and HBeAb. HBeAg prevalence declined steadily
from 27.7% among population age 18-35 years old to 6.8% among population age 55
74 years old. The single factor analysis was used for 16 possible risk factors
and multivariate analysis showed that five risk factors were significantly
related to HBV infection. HBV infection is a serious public health problem among
adult population in Henan. Strengthening administrative regulations of medical
practices, especially in rural areas, and providing health education propaganda
to the public of HBV infection should be given more attention on public health
policy. J. Med. Virol. 89:450-457, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27504587
TI - DNA-reactive B cells in lupus.
AB - IgG anti-DNA antibodies are both diagnostic and pathogenic for systemic lupus
erythematosus (SLE). They contribute to tissue inflammation through direct tissue
binding and to systemic inflammation through activation of Toll-like receptors by
nucleic acid-containing immune complexes. IgG DNA-reactive antibodies originate
when B cell tolerance mechanisms are impaired. The heterogeneous immune
perturbations in SLE lead to the survival and activation of DNA-reactive B cells
in various B cell subsets at distinct stages of B cell maturation and
differentiation. We propose that the spectrum of B cell alterations and failed
tolerance mechanisms for DNA-reactive B cells in lupus patients is best
understood by studying genetic risk alleles. This implies that the B cells
producing IgG anti-DNA antibodies and the failed tolerance mechanisms(s) will
differ across patients. A better understanding of these differences should lead
to better patient stratification, improved outcomes of clinical trials, and the
identification of novel therapeutic targets.
PMID- 27504588
TI - AIRE-mutations and autoimmune disease.
AB - The gene causing the severe organ-specific autoimmune disease autoimmune
polyendocrine syndrome type-1 (APS-1) was identified in 1997 and named autoimmune
regulator (AIRE). AIRE plays a key role in shaping central immunological
tolerance by facilitating negative selection of T cells in the thymus, building
the thymic microarchitecture, and inducing a specific subset of regulatory T
cells. So far, about 100 mutations have been identified. Recent advances suggest
that certain mutations located in the SAND and PHD1 domains exert a dominant
negative effect on wild type AIRE resulting in milder seemingly common forms of
autoimmune diseases, including pernicious anemia, vitiligo and autoimmune thyroid
disease. These findings indicate that AIRE also contribute to autoimmunity in
more common organ-specific autoimmune disorders.
PMID- 27504589
TI - Potential preadaptation to anthropogenic pollution: evidence from a common
quantitative trait locus for zinc and cadmium tolerance in metallicolous and
nonmetallicolous accessions of Arabidopsis halleri.
AB - As a drastic environmental change, metal pollution may promote the rapid
evolution of genetic adaptations contributing to metal tolerance. In Arabidopsis
halleri, genetic bases of zinc (Zn) and cadmium (Cd) tolerance have been
uncovered only in a metallicolous accession, although tolerance is species-wide.
The genetic determinants of Zn and Cd tolerance in a nonmetallicolous accession
were thus investigated for the first time. The genetic architecture of tolerance
was investigated in a nonmetallicolous population (SK2) by using first backcross
progeny obtained from crosses between SK2 and Arabidopsis lyrata petraea, a
nonmetallophyte species. Only one significant and common quantitative trait locus
(QTL) region was identified explaining 22.6% and 31.2% of the phenotypic
variation for Zn and Cd tolerance, respectively. This QTL co-localized with HEAVY
METAL ATPASE 4 (AhHMA4), which was previously validated as a determinant of Zn
and Cd tolerance in a metallicolous accession. Triplication and high expression
of HMA4 were confirmed in SK2. In contrast, gene duplication and high expression
of METAL TOLERANT PROTEIN 1A (MTP1A), which was previously associated with Zn
tolerance in a metallicolous accession, were not observed in SK2. Overall, the
results support the role of HMA4 in tolerance capacities of A. halleri that may
have pre-existed in nonmetallicolous populations before colonization of metal
polluted habitats. Preadaptation to metal-contaminated sites is thus discussed.
PMID- 27504590
TI - Clinician's Commentary on Desveaux et al.(1).
PMID- 27504591
TI - Left and right ventricular kinetic energy using time-resolved versus time-average
ventricular volumes.
AB - PURPOSE: To measure the effects of using time-resolved (TR) versus time-averaged
(TA) ventricular segmentation on four-dimensional flow-sensitive (4D flow)
magnetic resonance imaging (MRI) kinetic energy (KE) calculations. MATERIALS AND
METHODS: Right (RV) and left (LV) ventricular KE was calculated from 4D flow MRI
data acquired at 3.0T in 10 healthy volunteers and five subjects with cardiac
disease using TR and TA segmentation. KE was calculated from the mass of blood
within the ventricles multiplied by the velocities squared. Differences in TR and
TA KE and interobserver variability were quantified with Bland-Altman analysis.
RESULTS: In healthy volunteers, peak systolic RV KE (KERV ) were 4.89 +/- 1.49 mJ
using TR and 5.53 +/- 1.62 mJ using TA segmentation (P = 0.016); peak systolic LV
KE (KELV ) were 3.29 +/- 0.96 mJ and 4.16 +/- 1.26 mJ (P = 0.005). Peak diastolic
KERV were 3.33 +/- 0.90 mJ (TR) and 3.61 +/- 1.12 mJ (TA) (P = 0.082), while peak
diastolic KELV were 4.90 +/- 1.49 mJ and 5.31 +/- 1.59 mJ (P = 0.044). In patient
volunteers, peak systolic KERV were 4.34 +/- 3.78 mJ using TR and 4.88 +/- 3.98
mJ using TA segmentation (P = 0.26); peak systolic KELV were 4.39 +/- 4.21 mJ and
4.36 +/- 3.84 mJ (P = 0.91). Peak diastolic KERV were 3.34 +/- 2.08 mJ (TR) and
4.05 +/- 1.12 mJ (TA) (P = 0.08), while peak diastolic KELV were 4.34 +/- 5.11 mJ
and 4.06 +/- 3.47 mJ (P = 0.75). Interobserver differences in KELV were greater
for TR than TA calculations; bias ranged from 3 +/- 30% for TA peak systolic KELV
to 36 +/- 30% for TR peak diastolic KELV . CONCLUSION: Although qualitatively
similar, KE values calculated through TA segmentation were consistently greater
than TR KE, with differences more pronounced during systole and in the LV. LEVEL
OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:821-828.
PMID- 27504592
TI - Nonpigmented hair removal using photodynamic therapy in animal model.
AB - BACKGROUND AND OBJECTIVE: Lasers have been successfully used for decades to
remove dark hair. However, laser removal of nonpigmented hair is challenging due
to the lack of chromophores. The aim of this study was to use photodynamic
therapy (PDT) to remove nonpigmented hair. STUDY DESIGN/MATERIAL AND METHODS: We
compared the efficacy of permanent hair reduction in white BALB/c and black
C57BL/6 mice treated with PDT or an 800-nm diode laser. We collected skin biopsy
specimens and investigated post-PDT histologic changes and molecular changes.
RESULTS: We observed keratin 15 staining in the bulge area and alkaline
phosphatase staining in the dermal papilla following PDT. We observed a
temporary, catagen-like transformation in nonpigmented hair follicles after PDT.
We observed apoptotic cells in the hair matrix after PDT. Irradiation with an 800
nm diode laser did not achieve nonpigmented hair removal. Multiple PDT sessions
achieved permanent reduction of nonpigmented hair. Interestingly, removal of
black hair using PDT was less efficient. CONCLUSION: Our results suggest that PDT
can damage the nonpigmented hair matrix, but not stem cells or dermal papillae.
Repeated PDT may impair the hair-regeneration capacity via a bystander effect on
bulge stem cells or dermal papillae. In this study, we found it was possible to
remove nonpigmented hair using PDT. Lasers Surg. Med. 48:748-762, 2016. (c) 2016
Wiley Periodicals, Inc.
PMID- 27504593
TI - Neurological, Metabolic, and Psychiatric Adverse Events in Children and
Adolescents Treated With Aripiprazole.
AB - Aripiprazole is a partial dopamine agonist with only minor neurological and
psychiatric adverse effects, making it a potential first-line drug for the
treatment of psychiatric disorders. However, the evidence of its use in children
and adolescents is rather sparse. The aim of this case study is to discuss
adverse drug reaction (ADR) reports concerning aripiprazole-associated
neurological and psychiatric events in children and adolescents. The ADR report
database at Danish Medicines Agency was searched for all ADRs involving children
and adolescents (<18 years) reported by the search term [aripiprazole] AND all
spontaneous reports since the introduction of aripiprazole in 2003 until December
31, 2015. Nineteen case reports were included in the study and included both
patients with psychotic disorders (PS group) and nonpsychotic disorders (non-PS
group). The PS group consisted of 5 patients with schizophrenia and psychoses,
not otherwise specified; and the non-PS group consisted of fourteen cases
including autism spectrum disorders, attention deficit and hyperactivity
disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported
adverse effects in the non-PS group were chronic insomnia, Parkinsonism,
behavioral changes psychoses, and weight gain, whereas the adverse effects in the
PS group was predominantly anxiety, convulsions, and neuroleptic malignant
syndrome. Although aripiprazole is considered safe and well tolerated in children
and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme
insomnia, and suicidal behavior has been reported to health authorities.
Clinicians should pay attention to these possible hazards when prescribing
aripiprazole to this vulnerable group of patients.
PMID- 27504594
TI - The culture of pretence: a hidden barrier to recognising, disclosing and ending
domestic violence.
AB - AIMS AND OBJECTIVES: To explore in detail how women perceived their experience of
domestic violence and leaving or ending the abuse. This research also examined
how service providers identified their professional role in assisting women to
end such relationships. BACKGROUND: Domestic violence against women continues to
occur internationally. Reliable statistics are difficult to capture because of
inconsistent definitions, contradictory methods of acquiring data and unreported
incidents. DESIGN: A qualitative study, undertaken in two phases, was conducted
in Australia. METHODS: Twelve women who had experienced domestic violence and
ended those relationships participated in one semistructured interview (Phase 1).
Twenty-five professionals from health, social sciences and law, whose work
included assisting women experiencing domestic violence, participated in three
focus groups (Phase 2). Thematic analysis guided by a narrative inquiry approach
forms the framework for information collection and interpretation of data in this
project. FINDINGS: The barriers that impede women from disclosing abuse and
taking action to end domestic violence are complex and varied between
participants. Women did not always acknowledge or realise their relationship was
precarious and often denied or minimised the abuse to cope with the domestic
violence. Professionals identified that women did not always identify or
acknowledge abuse inherent in their relationship although this delayed the
provision of appropriate services. CONCLUSION: Whether women disclose abuse or
deny violence in their relationship, acceptance by service providers and the
offer of support is crucial to assisting women in violent relationships.
RELEVANCE TO CLINICAL PRACTICE: It is hoped that the findings may assist health
practitioners, including nurses, to provide nonjudgemental support to women
experiencing domestic violence whether women acknowledge the abusive relationship
or not.
PMID- 27504595
TI - Colorimetric determination of Timolol concentration based on localized surface
plasmon resonance of silver nanoparticles.
AB - In this work, a rapid and simple colorimetric method based on the surface plasmon
resonance of silver nanoparticles (AgNPs) was developed for the detection of the
drug Timolol. The method used is based on the interaction of Timolol with the
surface of the as-synthesized AgNPs, which promotes aggregation of the
nanoparticles. This aggregation exploits the surface plasmon resonance through
the electric dipole-dipole interaction and coupling among the agglomerated
particles, hence bringing forth distinctive changes in the spectra as well as the
color of colloidal silver. UV-vis spectrophotometery was used to monitor the
changes of the localized surface plasmon resonance of AgNPs at wavelengths of 400
and 550 nm. The developed colorimetric sensor has a wide dynamic range of 1.0 *
10(-7) M-1.0 * 10(-3) M for detection of Timolol with a low detection limit of
1.2 * 10(-6) M. The proposed method was successfully applied for the
determination of Timolol concentration in ophthalmic eye-drop solution with a
response time lower than 40 s.
PMID- 27504596
TI - Separating neural activity associated with emotion and implied motion: An fMRI
study.
AB - Previous research provides evidence for an emo-motoric neural network allowing
emotion to modulate activity in regions of the nervous system related to
movement. However, recent research suggests that these results may be due to the
movement depicted in the stimuli. The purpose of the current study was to
differentiate the unique neural activity of emotion and implied motion using
functional MRI. Thirteen healthy participants viewed 4 sets of images: (a)
negative stimuli implying movement, (b) negative stimuli not implying movement,
(c) neutral stimuli implying movement, and (d) neutral stimuli not implying
movement. A main effect for implied motion was found, primarily in regions
associated with multimodal integration (bilateral insula and cingulate), and
visual areas that process motion (bilateral middle temporal gyrus). A main effect
for emotion was found primarily in occipital and parietal regions, indicating
that emotion enhances visual perception. Surprisingly, emotion also activated the
left precentral gyrus, a motor region. These results demonstrate that emotion
elicits activity above and beyond that evoked by the perception of implied
movement, but that the neural representations of these characteristics overlap.
(PsycINFO Database Record
PMID- 27504597
TI - Emotional memory: No source memory without old-new recognition.
AB - Findings reported in the memory literature suggest that the emotional components
of an encoding episode can be dissociated from nonemotional memory. In
particular, it has been found that the previous association with threatening
events can be retrieved in aversive conditioning even in the absence of item
identification. In the present study, we test whether emotional source memory can
be independent of item recognition. Participants saw pictures of snakes paired
with threatening and nonthreatening context information (poisonousness or
nonpoisonousness). In the source memory test, participants were required to
remember whether a snake was associated with poisonousness or nonpoisonousness. A
simple extension of a well-established multinomial source monitoring model was
used to measure source memory for unrecognized items. By using this model, it was
possible to assess directly whether participants were able to associate a
previously seen snake with poisonousness or nonpoisonousness even if the snake
itself was not recognized as having been presented during the experiment. In 3
experiments, emotional source memory was only found for recognized items. While
source memory for recognized items differed between emotional and nonemotional
information, source memory for unrecognized items was equally absent for
emotional and nonemotional information. We conclude that emotional context
information is bound to item representations and cannot be retrieved in the
absence of item recognition. (PsycINFO Database Record
PMID- 27504598
TI - Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon
Local Administration in Mouse Brain.
AB - The use of siRNA-based therapies for the treatment of neurodegenerative disease
requires efficient, nontoxic distribution to the affected brain parenchyma,
notably the striatum and cortex. Here, we describe the synthesis and activity of
a fully chemically modified siRNA that is directly conjugated to docosahexaenoic
acid (DHA), the most abundant polyunsaturated fatty acid in the mammalian brain.
DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral
striatum and cortex following a single, intrastriatal injection (ranging from 6
60 MUg). Within these tissues, DHA conjugation promotes internalization by both
neurons and astrocytes. We demonstrate efficient and specific silencing of
Huntingtin mRNA expression in both the ipsilateral striatum (up to 73%) and
cortex (up to 51%) after 1 week. Moreover, following a bilateral intrastriatal
injection (60 MUg), we achieve up to 80% silencing of a secondary target,
Cyclophilin B, at both the mRNA and protein level. Importantly, DHA-hsiRNAs do
not induce neural cell death or measurable innate immune activation following
administration of concentrations over 20 times above the efficacious dose. Thus,
DHA conjugation is a novel strategy for improving siRNA activity in mouse brain,
with potential to act as a new therapeutic platform for the treatment of
neurodegenerative disorders.
PMID- 27504599
TI - Are Physicians Influenced by Their Own Specialty Society's Guidelines Regarding
Mammography Screening? An Analysis of Nationally Representative Data.
AB - OBJECTIVE: The purpose of this study is to determine whether primary care
physicians were influenced by their own specialty society's mammography screening
recommendations after the 2009 U.S. Preventive Services Task Force's (USPSTF)
revised recommendations were released. MATERIALS AND METHODS: We performed an
analysis of cross-sectional nationally representative data for 2007-2012 from the
National Ambulatory Medical Care Survey (NAMCS). All office-based preventive
services visits for women 40 years old or older were included. Multivariate
regression analyses were used to identify changes over time in the mammography
referral rate per 1000 visits by physician specialty, adjusting for patient- and
office-level covariates. All analyses were weighted to account for the multistage
probability sampling design of NAMCS. RESULTS: Our analysis represented an
average of 35,947,290 office visits per year. Overall, between 2007-2008 and 2011
2012, mammography referral rates (per 1000 visits) decreased from 285 to 215
referrals (-25.0% adjusted change; p = 0.006). The largest decrease was among
family physicians (from 230 to 128; -49.0% adjusted change; p < 0.001), followed
by internal medicine physicians (from 135 to 79; -45.8% adjusted change; p =
0.038). No statistically significant change was noted among obstetricians and
gynecologists over time (from 476 to 419; -14.4% adjusted change; p = 0.23).
DISCUSSION: Family and internal medicine physicians, whose societies adhered to
2009 USPSTF recommendations for biennial screening starting at age 50 years,
showed statistically significant decreases in mammography referral rates over
time. Obstetricians and gynecologists, whose society continued to recommend
annual screening starting at age 40 years, showed no statistically significant
change in mammography referral rates over time. Physicians may be influenced by
their own society's recommendations, which may influence their shared decision
making discussions with patients.
PMID- 27504600
TI - Structural Impact of Single Ribonucleotide Residues in DNA.
AB - Single ribonucleotide intrusions represent the most common nonstandard nucleotide
type found incorporated in genomic DNA, yet little is known of their structural
impact. This lesion incurs genomic instability in addition to affecting the
physical properties of the DNA. To probe for structural and dynamic effects of
single ribonucleotides in various sequence contexts-AxC, CxG, and GxC, where x=rG
or dG-we report the structures of three single-ribonucleotide-containing DNA
duplexes and the corresponding DNA controls. The lesion subtly and locally
perturbs the structure asymmetrically on the 3' side of the lesion in both the
riboguanosine-containing and the complementary strand of the duplex. The
perturbations are mainly restricted to the sugar and phosphodiester backbone. The
ribose and 3'-downstream deoxyribose units are predominately in N-type
conformation; backbone torsion angles epsilon and/or zeta of the ribonucleotide
or upstream deoxyribonucleotide are affected. Depending on the flanking
sequences, the C2'-OH group forms hydrogen bonds with the backbone, 3'
neighboring base, and/or sugar. Interestingly, even in similar purine-rG
pyrimidine environments (A-rG-C and G-rG-C), a riboguanosine unit affects DNA in
a distinct manner and manifests different hydrogen bonds, which makes
generalizations difficult.
PMID- 27504601
TI - Spatial integration of E-cadherin adhesion, signalling and the epithelial
cytoskeleton.
AB - The characteristic tall and elongated shape of epithelial cells requires
specialized adhesive structures and a distinct organization of cytoskeletal
filaments. Cytoskeletal networks coordinate a precise organization of adhesive
and signalling complexes along cell-cell contacts and enable exquisite strong
cohesion among epithelial cells. E-cadherin, a calcium-dependent adhesion
receptor, is an essential adhesive system in epithelia and its dynamic regulation
and pathways that stabilize cell-cell adhesion have been extensively studied.
This review highlights the less understood mechanisms underlying how cadherin
receptor signalling drives cytoskeletal rearrangements which ultimately define
the epithelial cell shape. In the past two years, new insights identify specific
actin-binding proteins and regulators of the epithelial cytoskeleton as a
framework to support junction dynamics, plasticity and maintenance.
PMID- 27504602
TI - Synthesis, Electrochemistry, and Photophysical Studies of Ruthenium(II)
Polypyridine Complexes with D-pi-A-pi-D Type Ligands and Their Application
Studies as Organic Memories.
AB - A new class of ruthenium(II) polypyridine complexes with a series of D-pi-A-pi-D
type (D=donor, A=acceptor) ligands was synthesized and characterized by 1 H NMR
spectroscopy, mass spectrometry, and elemental analysis. The photophysical and
electrochemical properties of the complexes were also investigated. The newly
synthesized ruthenium(II) polypyridine complexes were found to exhibit two
intense absorption bands at both high-energy (lambda=333-369 nm) and low-energy
(lambda=520-535 nm) regions. They are assigned as intraligand (IL) pi->pi*
transitions of the bipyridine (bpy) and pi-conjugated bpy ligands, and IL charge
transfer (CT) transitions from the donor to the acceptor moiety with mixing of
dpi(RuII )->pi*(bpy) and dpi(RuII )->pi*(L) MLCT characters, respectively. In
addition, all complexes were demonstrated to exhibit intense red emissions at
approximately lambda=727-744 nm in degassed dichloromethane at 298 K or in n
butyronitrile glass at 77 K. Nanosecond transient absorption (TA) spectroscopy
has also been carried out, establishing the presence of the charge-separated
state. In order to understand the electrochemical properties of the complexes,
cyclic voltammetry has also been performed. Two quasi-reversible oxidation
couples and three quasi-reversible reduction couples were observed. One of the
ruthenium(II) complexes has been utilized in the fabrication of memory devices,
in which an ON/OFF current ratio of over 104 was obtained.
PMID- 27504603
TI - Trauma in Veterans With Substance Use Disorder: Similar Treatment Need Among
Urban and Rural Residents.
AB - PURPOSE: The objective of this study is to determine whether rural residence is
associated with trauma exposure or posttraumatic stress disorder symptoms among
military veterans seeking treatment for substance use disorder (SUD) through the
Department of Veterans Affairs (VA), Delivering mental health services to
veterans in rural areas is a challenge, so identifying differences in the causes
and outcomes of trauma exposure would assist in effectively targeting service
delivery. METHODS: Veterans (N = 196) entering SUD treatment at 3 Midwestern VA
treatment centers were designated as either urban or rural, based on rural-urban
commuting area (RUCA) codes. The veterans completed the Life Events Checklist,
the Posttraumatic Stress Disorder Checklist, and the Addiction Severity Index's
psychiatric status subscale. Hypothesized relationships between rural-urban
residence and both trauma exposure and symptomology were tested using independent
samples t tests, chi-square tests, and ordinary least squares regression.
FINDINGS: The range of traumatic experiences was similar between rural and urban
veterans, and rural-urban residence was not significantly associated with the
overall array of traumas experienced or the symptom measures' overall scores or
subscores. Of 17 possible traumatic lifetime experiences, rural veterans differed
from urban veterans on only 2, reporting significantly lower rates of
transportation accidents and unwanted sexual experiences. CONCLUSIONS: In both
the causes of trauma and the need for treatment, veterans residing in rural areas
differ little from their urban counterparts.
PMID- 27504604
TI - Fe-Catalyzed Cross-Coupling Reaction of Vinylic Ethers with Aryl Grignard
Reagents.
AB - Iron-catalyzed cross-coupling reaction of vinylic ethers with aryl Grignard
reagents is described. The reaction proceeded at room temperature with catalytic
amounts of an iron salt without the aid of costly ligands and additives. In this
catalytic system, vinylic C-O bonds were preferentially cleaved over aromatic C-O
bonds of aryl ethers or aryl sulfonates.
PMID- 27504606
TI - Time trends in the incidence of oesophageal cancer in Asia: Variations across
populations and histological types.
AB - OBJECTIVE: We aimed to assess temporal trends in incidence rates of oesophageal
cancer in Asian countries. MATERIALS AND METHODS: Using data from the Cancer
Incidence in Five Continents series, we examined the temporal trends in incidence
rates of oesophageal cancer by population and histological type in seven Asian
countries in 1988-2007. Age-period-cohort analyses estimated the overall annual
percentage changes (net drifts) and their 95% confidence intervals (CIs) in
incidence rates. RESULTS: The age-standardised incidence rate of oesophageal
cancer declined in most Asian populations, but remained relatively unchanged in
Japan and Israel. The rate of oesophageal squamous cell carcinoma decreased in
Hong Kong, Singapore and Israel, but was stable in Japan. The net drifts were
statistically significant in men in Hong Kong (-3.4%, 95% CI: -6.1%, -0.7%) and
in women in Singapore (-10.1%, 95% CI: -14.4%, -5.5%). The age-standardised
incidence rates of oesophageal adenocarcinoma were below 2 and 0.5 per 100 000 in
men and women, respectively, across all periods in the all registers containing
valid data on histological type. The age-standardised incidence rate of
oesophageal adenocarcinoma slightly increased in Japan, Singapore, and Israel,
although the net drift was statistically significant only in Israeli men (4.9%,
95% CI: 0.8%, 9.1%). CONCLUSION: The overall incidence rates of oesophageal
cancer declined in most Asian countries, which is due to a decrease in
oesophageal squamous cell carcinoma incidence. However, attention needs to be
paid to a probable beginning of an increasing incidence of oesophageal
adenocarcinoma in Asia.
PMID- 27504605
TI - Inflammatory biomarkers, aspirin, and risk of colorectal cancer: Findings from
the physicians' health study.
AB - BACKGROUND: Chronic inflammation has been implicated in colorectal
carcinogenesis. However, the associations between plasma inflammatory markers and
risk of colorectal cancer have been inconsistent. METHODS: In a nested case
control study in the Physicians' Health Study, we prospectively investigated the
associations of plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor
necrosis factor receptor 2 (TNFR-2) with risk of colorectal cancer, and whether
aspirin modified these associations among 268 colorectal cancer patients and 446
age- and smoking-matched controls. RESULTS: In multivariate-adjusted models,
plasma levels of CRP, IL-6 and TNFR-2 were not significantly associated with risk
of colorectal cancer, although a positive trend was observed for TNFR-2
(RRhighestvs.lowestquartile=1.55; 95% CI=0.95-2.54; Ptrend=0.05). We observed a
statistically significant association between elevated TNFR-2 levels and
colorectal cancer risk in the placebo arm (RRhighestvs.lowesttertile=1.77; 95%
CI=1.02-3.06; Ptrend=0.02), but not in the aspirin arm (Ptrend=0.72). However,
the interaction between TNFR-2 and aspirin was not statistically significant
(Pinteraction=0.34). CONCLUSION: Plasma inflammatory markers were not
significantly associated with colorectal cancer risk among men, though there was
a statistically non-significant positive trend between TNFR-2 and colorectal
cancer risk. More studies are required to understand the relationship between the
role of TNFalpha pathway, aspirin, and colorectal cancer risk.
PMID- 27504607
TI - C-N Bond Formation from a Masked High-Valent Copper Complex Stabilized by Redox
Non-Innocent Ligands.
AB - The reactivity of a stable copper(II) complex bearing fully oxidized
iminobenzoquinone redox ligands towards nucleophiles is described. In sharp
contrast with its genuine low-valent counterpart bearing reduced ligands, this
complex performs high-yielding C-N bond formations. Mechanistic studies suggest
that this behavior could stem from a mechanism akin to reductive elimination
occurring at the metal center but facilitated by the ligand: it is proposed that
a masked high oxidation state of the metal can be stabilized as a lower
copper(II) oxidation state by the redox ligands without forfeiting its ability to
behave as a high-valent copper(III) center. These observations are substantiated
by a combination of advanced EPR spectroscopy techniques with DFT studies. This
work sheds light on the potential of redox ligands as promoters of unusual
reactivities at metal centers and illustrates the concept of masked high-valent
metallic species.
PMID- 27504608
TI - Dedicator of Cytokinesis 2 in Cell Signaling Regulation and Disease Development.
AB - Dedicator of cytokinesis 2 (DOCK2) is a CDM family protein containing DOCK
homology region (DHR)-1 and DHR-2, Src-homology 3 (SH3) domain, and C-terminal
polybasic amino acid cluster. The CDM family consists of 11 mammalian members and
is classified into four subfamilies, the DOCK-A, -B, -C, and -D. DOCK2 is a
member of DOCK-A subfamily and an atypical guanine exchange factor regulating the
loading of GTP to activate Rac. It is primarily found in peripheral blood,
spleen, and thymus and mainly expressed in lymphocytes and macrophages of various
organs. DOCK2 is also expressed in microglial in brain and is induced in
neointima smooth muscle following vascular injury. Functionally, DOCK2 is
involved in cell motility, polarity, adhesion, proliferation, and apoptosis. It
is essential for lymphocyte migration and activation as well as neutrophil
chemotaxis. DOCK2 also regulates the differentiation of natural killer T cells,
type 2 T helper cells, and plasmacytoid dendritic cells. In addition, it is
important for the growth of B cell lymphoma and prostate cancer cells. Deletion
of DOCK2 enables long-term cardiac allograft survival. Moreover, DOCK2 is
associated with the Alzheimer Disease, HIV development, and the early-onset of
invasive infections. Recently, we found that DOCK2 plays a critical role in SMC
phenotypic modulation and vascular remodeling. In this review, we will briefly
summarize recent advancement of DOCK2 function. J. Cell. Physiol. 232: 1931-1940,
2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27504609
TI - Differential modulation of visual object processing in dorsal and ventral stream
by stimulus visibility.
AB - As a functional organization principle in cortical visual information processing,
the influential 'two visual systems' hypothesis proposes a division of labor
between a dorsal "vision-for-action" and a ventral "vision-for-perception"
stream. A core assumption of this model is that the two visual streams are
differentially involved in visual awareness: ventral stream processing is closely
linked to awareness while dorsal stream processing is not. In this functional
magnetic resonance imaging (fMRI) study with human observers, we directly probed
the stimulus-related information encoded in fMRI response patterns in both visual
streams as a function of stimulus visibility. We parametrically modulated the
visibility of face and tool stimuli by varying the contrasts of the masks in a
continuous flash suppression (CFS) paradigm. We found that visibility -
operationalized by objective and subjective measures - decreased proportionally
with increasing log CFS mask contrast. Neuronally, this relationship was closely
matched by ventral visual areas, showing a linear decrease of stimulus-related
information with increasing mask contrast. Stimulus-related information in dorsal
areas also showed a dependency on mask contrast, but the decrease rather followed
a step function instead of a linear function. Together, our results suggest that
both the ventral and the dorsal visual stream are linked to visual awareness, but
neural activity in ventral areas more closely reflects graded differences in
awareness compared to dorsal areas.
PMID- 27504610
TI - "Cognitive, emotion control, and motor performance of adolescents in the NCANDA
study: Contributions from alcohol consumption, age, sex, ethnicity, and family
history of addiction": Correction to Sullivan et al. (2016).
AB - Reports an error in "Cognitive, emotion control, and motor performance of
adolescents in the NCANDA study: Contributions from alcohol consumption, age,
sex, ethnicity, and family history of addiction" by Edith V. Sullivan, Ty
Brumback, Susan F. Tapert, Rosemary Fama, Devin Prouty, Sandra A. Brown, Kevin
Cummins, Wesley K. Thompson, Ian M. Colrain, Fiona C. Baker, Michael D. De
Bellis, Stephen R. Hooper, Duncan B. Clark, Tammy Chung, Bonnie J. Nagel, B.
Nolan Nichols, Torsten Rohlfing, Weiwei Chu, Kilian M. Pohl and Adolf Pfefferbaum
(Neuropsychology, 2016[May], Vol 30[4], 449-473). A problem with a computation to
invert speed scores is noted and explained in this correction. All statements
indicating group differences in speed scores, as well as Table 5 and Figure 8A,
have been corrected in the online version of this article. (The following
abstract of the original article appeared in record 2016-00613-001.) OBJECTIVE:
To investigate development of cognitive and motor functions in healthy
adolescents and to explore whether hazardous drinking affects the normal
developmental course of those functions. METHOD: Participants were 831
adolescents recruited across 5 United States sites of the National Consortium on
Alcohol and NeuroDevelopment in Adolescence 692 met criteria for no/low alcohol
exposure, and 139 exceeded drinking thresholds. Cross-sectional, baseline data
were collected with computerized and traditional neuropsychological tests
assessing 8 functional domains expressed as composite scores. General additive
modeling evaluated factors potentially modulating performance (age, sex,
ethnicity, socioeconomic status, and pubertal developmental stage). RESULTS:
Older no/low-drinking participants achieved better scores than younger ones on 5
accuracy composites (general ability, abstraction, attention, emotion, and
balance). Speeded responses for attention, motor speed, and general ability were
sensitive to age and pubertal development. The exceeds-threshold group
(accounting for age, sex, and other demographic factors) performed significantly
below the no/low-drinking group on balance accuracy and on general ability,
attention, episodic memory, emotion, and motor speed scores and showed evidence
for faster speed at the expense of accuracy. Delay Discounting performance was
consistent with poor impulse control in the younger no/low drinkers and in
exceeds-threshold drinkers regardless of age. CONCLUSIONS: Higher achievement
with older age and pubertal stage in general ability, abstraction, attention,
emotion, and balance suggests continued functional development through
adolescence, possibly supported by concurrently maturing frontal, limbic, and
cerebellar brain systems. Determination of whether low scores by the exceeds
threshold group resulted from drinking or from other preexisting factors requires
longitudinal study.
PMID- 27504611
TI - [Medical Studies + Internship + Vocational Training = A Complete Ophthalmic
Surgeon? A Theoretical Analysis of the Ophthalmic Surgery Training from the
Perspective of Medical and Educational Sciences].
AB - "Let's have the courage to train young doctors to conduct ophthalmic surgery!" -
This is the final plea of this theoretical article, which appeals for greater
collaboration between medical and educational sciences in the training of
ophthalmic surgeons. It will be discussed whether surgery-based training is
adequate, from the point of view of both medical knowledge and learning theory.
Standard requirements for the specialist qualification in ophthalmic surgery are
presented for Bavaria, Austria and Switzerland; these are then compared and
contrasted with the experience-based practice of vocational training. Assuming
that vocational training can be understood as providing the context for action
oriented learning, the relevance of procedural knowledge will be discussed for
the development of practical surgical skills. A model for expertise in ophthalmic
surgery will be outlined. Instructors' didactic skills and expertise will be
discussed in relation to the requirements and guidelines for receiving the
license to train assistants. In general, the article highlights the relevance of
performance in learning surgery, and calls for the provision of sufficient
possibilities to learn surgery in the course of assistant doctors' vocational
training. This article addresses those who are involved in ophthalmologists' and
ophthalmic surgeons' vocational training (e.g. medical instructors, medical
associations, assistant doctors) and who welcome thought-provoking impulses from
unfamiliar academic disciplines on key questions and concerns in practical
vocational training.
PMID- 27504612
TI - [Are Visual Field Defects Reversible? - Visual Rehabilitation with Brains].
AB - Visual field defects are considered irreversible because the retina and optic
nerve do not regenerate. Nevertheless, there is some potential for recovery of
the visual fields. This can be accomplished by the brain, which analyses and
interprets visual information and is able to amplify residual signals through
neuroplasticity. Neuroplasticity refers to the ability of the brain to change its
own functional architecture by modulating synaptic efficacy. This is actually the
neurobiological basis of normal learning. Plasticity is maintained throughout
life and can be induced by repetitively stimulating (training) brain circuits.
The question now arises as to how plasticity can be utilised to activate residual
vision for the treatment of visual field loss. Just as in neurorehabilitation,
visual field defects can be modulated by post-lesion plasticity to improve vision
in glaucoma, diabetic retinopathy or optic neuropathy. Because almost all
patients have some residual vision, the goal is to strengthen residual capacities
by enhancing synaptic efficacy. New treatment paradigms have been tested in
clinical studies, including vision restoration training and non-invasive
alternating current stimulation. While vision training is a behavioural task to
selectively stimulate "relative defects" with daily vision exercises for the
duration of 6 months, treatment with alternating current stimulation (30 min.
daily for 10 days) activates and synchronises the entire retina and brain. Though
full restoration of vision is not possible, such treatments improve vision, both
subjectively and objectively. This includes visual field enlargements, improved
acuity and reaction time, improved orientation and vision related quality of
life. About 70 % of the patients respond to the therapies and there are no
serious adverse events. Physiological studies of the effect of alternating
current stimulation using EEG and fMRI reveal massive local and global changes in
the brain. These include local activation of the visual cortex and global
reorganisation of neuronal brain networks. Because modulation of neuroplasticity
can strengthen residual vision, the brain deserves a better reputation in
ophthalmology for its role in visual rehabilitation. For patients, there is now
more light at the end of the tunnel, because vision loss in some areas of the
visual field defect is indeed reversible.
PMID- 27504613
TI - The fabrication of well-interconnected polycaprolactone/hydroxyapatite composite
scaffolds, enhancing the exposure of hydroxyapatite using the wire-network
molding technique.
AB - In this study, the fabrication method was proposed for the well-interconnected
polycaprolactone/hydroxyapatite composite scaffold with exposed hydroxyapatite
using modified WNM technique. To characterize well-interconnected scaffolds in
terms of hydroxyapatite exposure, several assessments were performed as follows:
morphology, mechanical property, wettability, calcium ion release, and cell
response assessments. The results of these assessments were compared with those
of control scaffolds which were fabricated by precision extruding deposition
(PED) apparatus. The control PED scaffolds have interconnected pores with
nonexposed hydroxyapatite. Consequently, cell attachment of proposed WNM scaffold
was improved by increased hydrophilicity and surface roughness of scaffold
surface resulting from the exposure of hydroxyapatite particles and fabrication
process using powders. Moreover, cell proliferation and differentiation of WNM
scaffold were increased, because the exposure of hydroxyapatite particles may
enhance cell adhesion and calcium ion release. (c) 2016 Wiley Periodicals, Inc. J
Biomed Mater Res Part B: Appl Biomater, 105B: 2315-2325, 2017.
PMID- 27504614
TI - Application of Concept Mapping as a Visual Thinking Strategy in an Asynchronous
Online Graduate Informatics Course.
PMID- 27504615
TI - Member Highlights at New England Nursing Informatics Consortium's 2016 Annual
Symposium.
PMID- 27504616
TI - Integrating an Academic Electronic Health Record: Challenges and Success
Strategies.
PMID- 27504617
TI - Eco-friendly larvicides from Indian plants: Effectiveness of lavandulyl acetate
and bicyclogermacrene on malaria, dengue and Japanese encephalitis mosquito
vectors.
AB - Mosquitoes (Diptera: Culicidae) are a key threat for millions of people and
animals worldwide, since they act as vectors for devastating pathogens and
parasites, including malaria, dengue, Japanese encephalitis, filiariasis and Zika
virus. Mosquito young instars are usually targeted using organophosphates, insect
growth regulators and microbial agents. Indoor residual spraying and insecticide
treated bed nets are also employed. However, these chemicals have negative
effects on human health and the environment and induce resistance in a number of
vectors. In this scenario, newer and safer tools have been recently implemented
to enhance mosquito control. The concrete potential of screening plant species as
sources of metabolites for entomological and parasitological purposes is worthy
of attention, as recently elucidated by the Y. Tu's example. Here we investigated
the toxicity of Heracleum sprengelianum (Apiaceae) leaf essential oil and its
major compounds toward third instar larvae of the malaria vector Anopheles
subpictus, the arbovirus vector Aedes albopictus and the Japanese encephalitis
vector Culex tritaeniorhynchus. GC-MS analysis showed that EO major components
were lavandulyl acetate (17.8%) and bicyclogermacrene (12.9%). The EO was toxic
to A. subpictus, A. albopictus, and C. tritaeniorhynchus, with LC50 of 33.4, 37.5
and 40.9ug/ml, respectively. Lavandulyl acetate was more toxic to mosquito larvae
if compared to bicyclogermacrene. Their LC50 were 4.17 and 10.3ug/ml for A.
subpictus, 4.60 and 11.1ug/ml for A. albopictus, 5.11 and 12.5ug/ml for C.
tritaeniorhynchus. Notably, the EO and its major compounds were safer to three
non-target mosquito predators, Anisops bouvieri, Diplonychus indicus and Gambusia
affinis, with LC50 ranging from 206 to 4219ug/ml. Overall, this study highlights
that H. sprengelianum EO is a promising source of eco-friendly larvicides against
three important mosquito vectors with moderate toxicity against non-target
aquatic organisms.
PMID- 27504618
TI - Gestational diabetes: paradigm lost?
PMID- 27504621
TI - Ninety-First Annual Business Meeting.
PMID- 27504619
TI - Normal multiplanar movement of the spinal cord during unilateral and bilateral
straight leg raise: Quantification, mechanisms, and overview.
AB - The purpose of this investigation was to provide a full set of normal data
describing neural biomechanics within the vertebral canal in all three planes
with unilateral and bilateral SLR tests to allow for clinical comparison with
clinical cases. This is done following the notion that, due to neural continuum,
tensile forces are transmitted through the lumbosacral nerve roots and dura to
the conus medullaris (linear dependency principle). In this controlled radiologic
study 10 asymptomatic volunteers were scanned with 1.5T magnetic resonance
scanner (Siemens Magnetom Aera, Erlangen, Germany) using different scanning
sequences for planning and for measurement purposes. Conus displacement in both
antero-posterior direction (sagittal slices) and lateral direction (axial slices)
was quantified during unilateral passive left, right SLR, and bilateral SLR and
compared with the position of the conus in the neutral (anatomic) position. It is
shown that the conus medullaris displaced laterally and anteroposteriorly in
response to unilateral and bilateral SLRs. Pearson's correlations were higher
than 0.95 for both intra- and inter-observer reliability. The observed power was
higher than 0.99 for all the variables tested. Following this, the authors
conclude that lateral and antero-posterior displacement of conus medullaris into
the vertebral canal occurs consistently with unilateral and bilateral SLRs
following directions predicted by tension vectors. Summative information
collected in this line of research in neuroradiology is here presented. We
believe we have presented the first conclusive and complete full set of normal
data on non-invasive, in vivo, normative measurement of spinal cord displacement
with the SLR ever presented. (c) 2017 Orthopaedic Research Society. Published by
Wiley Periodicals, Inc. J Orthop Res 35:1335-1342, 2017.
PMID- 27504622
TI - One Hundred and Sixth Annual Council Meeting.
PMID- 27504623
TI - Chromosomal Spreading of Microsatellites and (TTAGGG)n Sequences in the
Characidium zebra and C. gomesi Genomes (Characiformes: Crenuchidae).
AB - Sex chromosome evolution involves the accumulation of repeat sequences such as
multigenic families, noncoding repetitive DNA (satellite, minisatellite, and
microsatellite), and mobile elements such as transposons and retrotransposons.
Most species of Characidium exhibit heteromorphic ZZ/ZW sex chromosomes; the W is
characterized by an intense accumulation of repetitive DNA including dispersed
satellite DNA sequences and transposable elements. The aim of this study was to
analyze the distribution pattern of 18 different tandem repeats, including
(GATA)n and (TTAGGG)n, in the genomes of C. zebra and C. gomesi, especially in
the C. gomesi W chromosome. In the C. gomesi W chromosome, weak signals were seen
for (CAA)10, (CAC)10, (CAT)10, (CGG)10, (GAC)10, and (CA)15 probes. (GA)15 and
(TA)15 hybridized to the autosomes but not to the W chromosome. The (GATA)n probe
hybridized to the short arms of the W chromosome as well as the (CG)15 probe. The
(GATA)n repeat is known to be a protein-binding motif. GATA-binding proteins are
necessary for the decondensation of heterochromatic regions that hold coding
genes, especially in some heteromorphic sex chromosomes that may keep genes
related to oocyte development. The (TAA)10 repeat is accumulated in the entire W
chromosome, and this microsatellite accumulation is probably involved in the sex
chromosome differentiation process and crossover suppression in C. gomesi. These
additional data on the W chromosome DNA composition help to explain the evolution
of sex chromosomes in Characidium.
PMID- 27504624
TI - Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in
Carbohydrate Active Enzymes.
AB - Carbohydrate active enzymes often contain auxiliary binding sites located either
on independent domains termed carbohydrate binding modules (CBMs) or as so-called
surface binding sites (SBSs) on the catalytic module at a certain distance from
the active site. The SBSs are usually critical for the activity of their cognate
enzyme, though they are not readily detected in the sequence of a protein, but
normally require a crystal structure of a complex for their identification. A
variety of methods, including affinity electrophoresis (AE), insoluble
polysaccharide pulldown (IPP) and surface plasmon resonance (SPR) have been used
to study auxiliary binding sites. These techniques are complementary as AE allows
monitoring of binding to soluble polysaccharides, IPP to insoluble
polysaccharides and SPR to oligosaccharides. Here we show that these methods are
useful not only for analyzing known binding sites, but also for identifying new
ones, even without structural data available. We further verify the chosen assays
discriminate between known SBS/CBM containing enzymes and negative controls.
Altogether 35 enzymes are screened for the presence of SBSs or CBMs and several
novel binding sites are identified, including the first SBS ever reported in a
cellulase. This work demonstrates that combinations of these methods can be used
as a part of routine enzyme characterization to identify new binding sites and
advance the study of SBSs and CBMs, allowing them to be detected in the absence
of structural data.
PMID- 27504625
TI - Clinical Q & A: Translating Therapeutic Temperature Management from Theory to
Practice.
PMID- 27504626
TI - Site-Specific Ligand Interactions Favor the Tetragonal Distortion of PbS
Nanocrystal Superlattices.
AB - We analyze the structure and morphology of mesocrystalline, body-centered
tetragonal (bct) superlattices of PbS nanocrystals functionalized with oleic
acid. On the basis of combined scattering and real space imaging, we derive a
three-dimensional (3D) model of the superlattice and show that the bct structure
benefits from a balanced combination of {100}PbS-{100}PbS and {111}PbS-{111}PbS
interactions between neighboring layers of nanocrystals, which uniquely
stabilizes this structure. These interactions are enabled by the coaxial
alignment of the atomic lattices of PbS with the superlattice. In addition, we
find that this preferential orientation is already weakly present within isolated
monolayers. By adding excess oleic acid to the nanocrystal solution, tetragonal
distortion is suppressed, and we observe assembly into a bilayered hexagonal
lattice reminiscent of a honeycomb with grain sizes of several micrometers.
PMID- 27504627
TI - Diallel Analysis and Growth Parameters as Selection Tools for Drought Tolerance
in Young Theobroma cacao Plants.
AB - This study aimed to estimate the combining ability, of T. cacao genotypes
preselected for drought tolerance through diallel crosses. The experiment was
conducted under greenhouse conditions at the Cacao Research Center (CEPEC),
Ilheus, Bahia, Brazil, in a completely randomized block design, in an
experimental arrangement 21 x 2 [21 complete diallel crosses and two water
regimes (control and stressed)]. In the control, soil moisture was kept close to
field capacity, with predawn leaf water potential (PsiWL) ranging from -0.1 to
0.5 MPa. In the drought regime, the soil moisture was reduced gradually by
decreasing the amount of water application until PsiWL reached -2.0 to -2.5 MPa.
Significant differences (p < 0.05) were observed for most morphological
attributes analyzed regarding progenies, water regime and their interactions. The
results of the joint diallel analysis revealed significant effects between
general combining ability (GCA) x water regimes and between specific combining
ability (SCA) x water regimes. The SCA 6 genetic material showed high general
combining ability for growth variables regardless of the water regime. In
general, the water deficit influenced the production of biomass in most of the
evaluated T. cacao crosses, except for SCA-6 x IMC-67, Catongo x SCA, MOC-01 x
Catongo, Catongo x IMC-67 and RB-40 x Catongo. Multivariate analysis showed that
stem diameter (CD), total leaf area (TLA), leaf dry biomass (LDB), stem dry
biomass (SDB), root dry biomass (RDB), total dry biomass (TDB), root length (RL),
root volume (RV), root diameter (RD) <1 mm and 1 <(RD) <2 mm were the most
important growth parameters in the separation of T. cacao genotypes in to
tolerant and intolerant to soil water deficit.
PMID- 27504628
TI - Soluble CD14 Enhances the Response of Periodontal Ligament Stem Cells to P.
gingivalis Lipopolysaccharide.
AB - Periodontal ligament stem cells (PDLSCs) are lacking membrane CD14, which is an
important component of lipopolysaccharide (LPS) signaling through toll-like
receptor (TLR) 4. In the present study we investigated the effect of soluble CD14
on the response of human PDLSCs to LPS of Porphyromonas (P.) gingivalis. Human
PDLSCs (hPDLSCs) were stimulated with P. gingivalis LPS in the presence or in the
absence of soluble CD14 (sCD14) and the production of interleukin (IL)-6,
chemokine C-X-C motif ligand 8 (CXCL8), and chemokine C-C motif ligand 2 (CCL2)
was measured. The response to P. gingivalis LPS was compared with that to TLR4
agonist Escherichia coli LPS and TLR2-agonist Pam3CSK4. The response of hPDLSCs
to both P. gingivalis LPS and E. coli LPS was significantly enhanced by sCD14. In
the absence of sCD14, no significant difference in the hPDLSCs response to two
kinds of LPS was observed. These responses were significantly lower compared to
that to Pam3CSK4. In the presence of sCD14, the response of hPdLSCs to P.
gingivalis LPS was markedly higher than that to E. coli LPS and comparable with
that to Pam3CSK4. The response of hPdLSCs to bacterial LPS is strongly augmented
by sCD14. Local levels of sCD14 could be an important factor for modulation of
the host response against periodontal pathogens.
PMID- 27504629
TI - Modeling of Large-Scale Functional Brain Networks Based on Structural
Connectivity from DTI: Comparison with EEG Derived Phase Coupling Networks and
Evaluation of Alternative Methods along the Modeling Path.
AB - In this study, we investigate if phase-locking of fast oscillatory activity
relies on the anatomical skeleton and if simple computational models informed by
structural connectivity can help further to explain missing links in the
structure-function relationship. We use diffusion tensor imaging data and alpha
band-limited EEG signal recorded in a group of healthy individuals. Our results
show that about 23.4% of the variance in empirical networks of resting-state
functional connectivity is explained by the underlying white matter architecture.
Simulating functional connectivity using a simple computational model based on
the structural connectivity can increase the match to 45.4%. In a second step, we
use our modeling framework to explore several technical alternatives along the
modeling path. First, we find that an augmentation of homotopic connections in
the structural connectivity matrix improves the link to functional connectivity
while a correction for fiber distance slightly decreases the performance of the
model. Second, a more complex computational model based on Kuramoto oscillators
leads to a slight improvement of the model fit. Third, we show that the
comparison of modeled and empirical functional connectivity at source level is
much more specific for the underlying structural connectivity. However, different
source reconstruction algorithms gave comparable results. Of note, as the fourth
finding, the model fit was much better if zero-phase lag components were
preserved in the empirical functional connectome, indicating a considerable
amount of functionally relevant synchrony taking place with near zero or zero
phase lag. The combination of the best performing alternatives at each stage in
the pipeline results in a model that explains 54.4% of the variance in the
empirical EEG functional connectivity. Our study shows that large-scale brain
circuits of fast neural network synchrony strongly rely upon the structural
connectome and simple computational models of neural activity can explain missing
links in the structure-function relationship.
PMID- 27504630
TI - IgM-Enriched Immunoglobulin Attenuates Systemic Endotoxin Activity in Early
Severe Sepsis: A Before-After Cohort Study.
AB - INTRODUCTION: Sepsis remains associated with a high mortality rate. Endotoxin has
been shown to influence viscoelastic coagulation parameters, thus suggesting a
link between endotoxin levels and the altered coagulation phenotype in septic
patients. This study evaluated the effects of systemic polyspecific IgM-enriched
immunoglobulin (IgM-IVIg) (Pentaglobin(r) [Biotest, Dreieich, Germany]) on
endotoxin activity (EA), inflammatory markers, viscoelastic and conventional
coagulation parameters. METHODS: Patients with severe sepsis were identified by
daily screening in a tertiary, academic, surgical ICU. After the inclusion of 15
patients, the application of IgM-IVIg (5 mg/kg/d over three days) was integrated
into the unit's standard operation procedure (SOP) to treat patients with severe
sepsis, thereby generating "control" and "IgM-IVIg" groups. EA assays,
thrombelastometry (ROTEM(r)) and impedance aggregometry (Multiplate(r)) were
performed on whole blood. Furthermore, routine laboratory parameters were
determined according to unit's standards. RESULTS: Data from 26 patients were
included. On day 1, EA was significantly decreased in the IgM-IVIg group
following 6 and 12 hours of treatment (0.51 +/-0.06 vs. 0.26 +/-0.07, p<0.05 and
0.51 +/-0.06 vs. 0.25 +/-0.04, p<0.05) and differed significantly compared with
the control group following 6 hours of treatment (0.26 +/-0.07 vs. 0.43 +/-0.07,
p<0.05). The platelet count was significantly higher in the IgM-IVIg group
following four days of IgM-IVIg treatment (200/nl +/-43 vs. 87/nl +/-20, p<0.05).
The fibrinogen concentration was significantly lower in the control group on day
2 (311 mg/dl +/-37 vs. 475 mg/dl +/-47 (p = 0.015)) and day 4 (307 mg/dl +/-35
vs. 420 mg/dl +/-16 (p = 0.017)). No differences in thrombelastometric or
aggregometric measurements, or inflammatory markers (interleukin-6 (IL-6),
leukocyte, lipopolysaccharide binding protein (LBP)) were observed. CONCLUSION:
Treatment with IgM-enriched immunoglobulin attenuates the EA levels in patients
with severe sepsis and might have an effect on septic thrombocytopenia and
fibrinogen depletion. Viscoelastic, aggregometric or inflammatory parameters were
not influenced. TRIAL REGISTRATION: clinicaltrials.gov NCT02444871.
PMID- 27504631
TI - Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the
Thalamus in OCD: A Retrospective Case Series.
AB - BACKGROUND: The current notion that cortico-striato-thalamo-cortical circuits are
involved in the pathophysiology of obsessive-compulsive disorder (OCD) has
instigated the search for the most suitable target for deep brain stimulation
(DBS). However, despite extensive research, uncertainty about the ideal target
remains with many structures being underexplored. The aim of this report is to
address a new target for DBS, the medial dorsal (MD) and the ventral anterior
(VA) nucleus of the thalamus, which has thus far received little attention in the
treatment of OCD. METHODS: In this retrospective trial, four patients (three
female, one male) aged 31-48 years, suffering from therapy-refractory OCD
underwent high-frequency DBS of the MD and VA. In two patients (de novo group)
the thalamus was chosen as a primary target for DBS, whereas in two patients
(rescue DBS group) lead implantation was performed in a rescue DBS attempt
following unsuccessful primary stimulation. RESULTS: Continuous thalamic
stimulation yielded no significant improvement in OCD symptom severity. Over the
course of thalamic DBS symptoms improved in only one patient who showed "partial
response" on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression
Inventory scores dropped by around 46% in the de novo group; anxiety symptoms
improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and
mood was observable. CONCLUSION: MD/VA-DBS yielded no adequate alleviation of
therapy-refractory OCD, the overall strategy in targeting MD/VA as described in
this paper can thus not be recommended in DBS for OCD. The magnocellular portion
of MD (MDMC), however, might prove a promising target in the treatment of mood
related and anxiety disorders.
PMID- 27504632
TI - Modelling Vulnerability and Range Shifts in Ant Communities Responding to Future
Global Warming in Temperate Forests.
AB - Global warming is likely leading to species' distributional shifts, resulting in
changes in local community compositions and diversity patterns. In this study, we
applied species distribution models to evaluate the potential impacts of
temperature increase on ant communities in Korean temperate forests, by testing
hypotheses that 1) the risk of extinction of forest ant species would increase
over time, and 2) the changes in species distribution ranges could drive upward
movements of ant communities and further alter patterns of species richness. We
sampled ant communities at 335 evenly distributed sites across South Korea and
modelled the future distribution range for each species using generalized
additive models. To account for spatial autocorrelation, autocovariate
regressions were conducted prior to generalized additive models. Among 29 common
ant species, 12 species were estimated to shrink their suitable geographic areas,
whereas five species would benefit from future global warming. Species richness
was highest at low altitudes in the current period, and it was projected to be
highest at the mid-altitudes in the 2080s, resulting in an upward movement of 4.9
m yr-1. This altered the altitudinal pattern of species richness from a monotonic
decrease curve (common in temperate regions) to a bell-shaped curve (common in
tropical regions). Overall, ant communities in temperate forests are vulnerable
to the on-going global warming and their altitudinal movements are similar to
other faunal communities.
PMID- 27504633
TI - The Promise of Mineralocorticoid Antagonism in Acute Kidney Injury.
AB - Acute kidney injury (AKI) is a major cause of morbidity and mortality in
hospitalized patients. Despite substantial progress being made in understanding
the mechanisms contributing to the pathophysiology of AKI, we have so far been
unsuccessful in devising adequate therapeutic strategies against the disease. A
growing body of evidence suggests that the activation of mineralocorticoid
receptors (MRs) may contribute to the exacerbation of AKI. Indeed, several
studies have demonstrated the potential of MR antagonists in preventing and
treating certain forms of experimental AKI. However, the main drawback of these
medications is their side-effect profile. This has been addressed with the
development of newer nonsteroidal MR antagonists, which have a comparable
therapeutic profile without the side effects. This mini review aims at providing
a brief overview of the rationale, potential benefits and challenges associated
with the use of MR antagonists, particularly the novel nonsteroidal MR blockers,
as therapy against AKI. (c) 2016 S. Karger AG, Basel.
PMID- 27504634
TI - Recovery from Borderline Personality Disorder: A Systematic Review of the
Perspectives of Consumers, Clinicians, Family and Carers.
AB - PURPOSE: Longitudinal studies support that symptomatic remission from Borderline
Personality Disorder (BPD) is common, but recovery from the disorder probably
involves a broader set of changes in psychosocial function over and above symptom
relief. A systematic review of literature on both symptomatic and personal
recovery from BPD was conducted including the views of consumers, clinicians,
family and carers. MATERIALS AND METHODS: A PRISMA guided systematic search
identified research examining the process of recovery from BPD. Longitudinal
studies with a follow-up period of five or more years were included to avoid
treatment effects. RESULTS: There were 19 studies, representing 11 unique cohorts
(1,122 consumers) meeting the review criteria. There was a limited focus on
personal recovery and the views of family and carers were absent from the
literature. Rates of remission and recovery differ depending upon individual and
methodological differences between studies. Data on symptomatic remission,
recurrence and diagnosis retainment suggests that BPD is a stable condition,
where symptomatic remission is possible and the likelihood of recurrence
following a period of remission is low. CONCLUSION: Symptomatic remission from
BPD is common. However, recovery including capacities such as engaging in
meaningful work was seldom described. Future research needs broader measures of
recovery as a sub-syndromal experience, monitoring consumer engagement in
meaningful vocation and relationships, with or without the limitations of BPD.
PMID- 27504635
TI - Protective Effect of ALA in Crushed Optic Nerve Cat Retinal Ganglion Cells Using
a New Marker RBPMS.
AB - In this study we first sought to determine whether RNA-binding protein with
multiple splicing (RBPMS) can serve as a specific marker for cat retina ganglion
cells (RGCs) using retrograde labeling and immunohistochemistry staining. RBPM
was then used as an RGC marker to study RGC survival after optic nerve crush
(ONC) and alpha-lipoic acid (ALA) treatment in cats. ALA treatment yielded a peak
density of RBPMS-alpha cells within the peak isodensity zone (>60/mm2) which did
not differ from ONC retinas. The area within the zone was significantly enlarged
(control: 2.3%, ONC: 0.06%, ONC+ALA: 0.1%). As for the 10-21/mm2 zone, ALA
treatment resulted in a significant increase in area (control: 34.5%, ONC: 12.1%,
ONC+ALA: 35.9%). ALA can alleviate crush-induced RGC injury.
PMID- 27504636
TI - Analysis of Two Putative Candida albicans Phosphopantothenoylcysteine
Decarboxylase / Protein Phosphatase Z Regulatory Subunits Reveals an Unexpected
Distribution of Functional Roles.
AB - Protein phosphatase Z (Ppz) is a fungus specific enzyme that regulates cell wall
integrity, cation homeostasis and oxidative stress response. Work on
Saccharomyces cerevisiae has shown that the enzyme is inhibited by Hal3/Vhs3
moonlighting proteins that together with Cab3 constitute the essential
phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme. In Candida albicans
CaPpz1 is also involved in the morphological changes and infectiveness of this
opportunistic human pathogen. To reveal the CaPpz1 regulatory context we searched
the C. albicans database and identified two genes that, based on the structure of
their S. cerevisiae counterparts, were termed CaHal3 and CaCab3. By pull down
analysis and phosphatase assays we demonstrated that both of the bacterially
expressed recombinant proteins were able to bind and inhibit CaPpz1 as well as
its C-terminal catalytic domain (CaPpz1-Cter) with comparable efficiency. The
binding and inhibition were always more pronounced with CaPpz1-Cter, indicating a
protective effect against inhibition by the N-terminal domain in the full length
protein. The functions of the C. albicans proteins were tested by their
overexpression in S. cerevisiae. Contrary to expectations we found that only
CaCab3 and not CaHal3 rescued the phenotypic traits that are related to
phosphatase inhibition by ScHal3, such as tolerance to LiCl or hygromycin B,
requirement for external K+ concentrations, or growth in a MAP kinase deficient
slt2 background. On the other hand, both of the Candida proteins turned out to be
essential PPCDC components and behaved as their S. cerevisiae counterparts:
expression of CaCab3 and CaHal3 rescued the cab3 and hal3 vhs3 S. cerevisiae
mutations, respectively. Thus, both CaHal3 and CaCab3 retained the PPCDC related
functions and have the potential for CaPpz1 inhibition in vitro. The fact that
only CaCab3 exhibits its phosphatase regulatory potential in vivo suggests that
in C. albicans CaCab3, but not CaHal3, acts as a moonlighting protein.
PMID- 27504637
TI - Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about
ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First
Phase of the ANRS 12249 TasP Cluster-Randomised Trial.
AB - BACKGROUND: The 2015 WHO recommendation of antiretroviral therapy (ART) for all
immediately following HIV diagnosis is partially based on the anticipated impact
on HIV incidence in the surrounding population. We investigated this approach in
a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu
Natal. We present findings from the first phase of the trial and report on uptake
of home-based HIV testing, linkage to care, uptake of ART, and community
attitudes about ART. METHODS AND FINDINGS: Between 9 March 2012 and 22 May 2014,
five clusters in the intervention arm (immediate ART offered to all HIV-positive
adults) and five clusters in the control arm (ART offered according to national
guidelines, i.e., CD4 count <= 350 cells/MUl) contributed to the first phase of
the trial. Households were visited every 6 mo. Following informed consent and
administration of a study questionnaire, each resident adult (>=16 y) was asked
for a finger-prick blood sample, which was used to estimate HIV prevalence, and
offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive
adults were referred to the trial clinic in their cluster. Those not linked to
care 3 mo after identification were contacted by a linkage-to-care team. Study
procedures were not blinded. In all, 12,894 adults were registered as eligible
for participation (5,790 in intervention arm; 7,104 in control arm), of whom
9,927 (77.0%) were contacted at least once during household visits. HIV status
was ever ascertained for a total of 8,233/9,927 (82.9%), including 2,569
ascertained as HIV-positive (942 tested HIV-positive and 1,627 reported a known
HIV-positive status). Of the 1,177 HIV-positive individuals not previously in
care and followed for at least 6 mo in the trial, 559 (47.5%) visited their
cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218)
initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3%
(83/196) had a CD4 count <= 350 cells/MUl at first visit, of whom 92.8% initiated
ART within 3 mo. Regarding attitudes about ART, 93% (8,802/9,460) of participants
agreed with the statement that they would want to start ART as soon as possible
if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2,028/6,656) (95%
CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to
care within 6 mo, and initiation of ART within 3 mo in those with CD4 count <=
350 cells/MUl did not differ significantly between the intervention and control
clusters. Selection bias related to noncontact could not be entirely excluded.
CONCLUSIONS: Home-based HIV testing was well received in this rural population,
although men were less easily contactable at home; immediate ART was acceptable,
with good viral suppression and retention. However, only about half of HIV
positive people accessed care within 6 mo of being identified, with nearly two
thirds accessing care by 12 mo. The observed delay in linkage to care would limit
the individual and public health ART benefits of universal testing and treatment
in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01509508.
PMID- 27504638
TI - Comparisons of the Tono-Pen(r) and Goldmann Applanation Tonometer in the
Measurement of Intraocular Pressure of Primary Open Angle Glaucoma Patients in a
Hospital Population in Southwest Nigeria.
AB - OBJECTIVE: The aim of this study was to compare intraocular pressure (IOP)
measured with the Tono-Pen(r) to that measured using the Goldmann applanation
tonometer (GAT) in patients with primary open angle glaucoma attending a glaucoma
clinic. SUBJECTS AND METHODS: A comparative clinic-based observational study was
conducted involving 75 patients (39 men and 36 women) attending a glaucoma clinic
in Southwest Nigeria. A pretested structured questionnaire was used to collect
sociodemographic data. The Tono-Pen and the GAT were used to measure the IOP in
each patient. Central corneal thickness (CCT) was measured with an ultrasonic
pachymeter, and the corrected GAT value was calculated for each patient. The Tono
Pen readings were compared with the uncorrected and corrected GAT readings.
Descriptive and comparative analyses were performed. Values for p < 0.05 were
considered statistically significant. RESULTS: The mean age of the participants
was 60.39 +/- 16.71 years. The mean IOP using the Tono-Pen was 21.1 +/- 6.8 mm Hg
versus the mean uncorrected GAT value of 17.1 +/- 6.9 mm Hg and the corrected GAT
value of 18.9 +/- 7.5 mm Hg. The mean CCT was 510.5 +/- 29.6 um. The mean
differences between the Tono-Pen reading and uncorrected and corrected GAT
readings were 3.9 +/- 2.6 and 2.1 +/- 3.5 mm Hg, respectively. Gender (Tono-Pen
vs. GAT; p = 0.981 vs. 0.437) and corneal thickness (p = 0.057) did not
significantly affect the IOP value. Of the 75 patients, 68 (90.7%) preferred the
Tono-Pen to the GAT. CONCLUSION: In this study, the Tono-Pen gave a higher value
for IOP than the uncorrected and corrected GAT values. Gender and corneal
thickness did not significantly affect the measurements. Most patients found the
Tono-Pen more acceptable than the GAT.
PMID- 27504639
TI - Real-Time Diffusion of Information on Twitter and the Financial Markets.
AB - Do spikes in Twitter chatter about a firm precede unusual stock market trading
activity for that firm? If so, Twitter activity may provide useful information
about impending financial market activity in real-time. We study the real-time
relationship between chatter on Twitter and the stock trading volume of 96 firms
listed on the Nasdaq 100, during 193 days of trading in the period from May 21,
2012 to September 18, 2013. We identify observations featuring firm-specific
spikes in Twitter activity, and randomly assign each observation to a ten-minute
increment matching on the firm and a number of repeating time indicators. We
examine the extent that unusual levels of chatter on Twitter about a firm portend
an oncoming surge of trading of its stock within the hour, over and above what
would normally be expected for the stock for that time of day and day of week. We
also compare the findings from our explanatory model to the predictive power of
Tweets. Although we find a compelling and potentially informative real-time
relationship between Twitter activity and trading volume, our forecasting
exercise highlights how difficult it can be to make use of this information for
monetary gain.
PMID- 27504640
TI - Do organizational expectations influence workers' implementation perceptions?
AB - The purpose of this article is to report on the use of empirically supported
treatments (ESTs) among clinical addiction workers, in order to relate the use of
ESTs to both perceived agency expectations and worker-level attitudes. We
recruited a convenience sample of 120 frontline workers within 4 agencies
providing addiction services in St. Louis. The results found that agency
expectations were related to clinician's reported use of ESTs, but were unrelated
to clinician attitudes. The regression results revealed that reported use of ESTs
was associated with openness to ESTs, but was not associated with favoring
clinical experience. Organizational leaders interested in using ESTs should send
clear, strong messages that they expect workers to use ESTs during clinical
practice. (PsycINFO Database Record
PMID- 27504641
TI - Violence risk assessment and psychological treatment in correctional and forensic
settings: Advances in research and practice.
AB - This article is an introduction to the special section "Correctional and Criminal
Justice Psychology." The eight articles in this issue advance the goals of
delivering and assessing psychological services within the legal and correctional
systems and achieving lasting change in individuals, groups, and systems.
(PsycINFO Database Record
PMID- 27504642
TI - The increasing influence of risk assessment on forensic patient review board
decisions.
AB - Previous studies of decisions about forensic patients' placement in secure
hospitals indicate some changes over time in the use of empirically supported
risk factors. Our aim was to investigate whether, in more recent cases, risk
assessment instruments were cited by a forensic patient review board or by the
clinicians who made recommendations to the board and whether there was evidence
of an association between risk assessment results and either dispositions or
recommendations. Among review board hearings held in 2009-2012 pertaining to 63
different maximum security patients found not criminally responsible on account
of mental disorder in Ontario, Canada, dispositions were most strongly associated
with psychiatrists' testimony, consistent with previous studies. However,
dispositions were associated with the scores on the Violence Risk Appraisal Guide
(VRAG), such that transferred patients had a lower risk of violent recidivism
than detained patients. An association between clinical opinions and risk
assessment results was also evident and significantly larger than in previous
research. There was no evidence that risk assessment was cited selectively in
higher risk cases or when scores were concordant with the review board decision.
This research may provide a baseline for studies of the effect of 2014
legislation introducing a high-risk designation for forensic patients in Canada.
We recommend further efforts to measure the effect of nonpharmacological
treatment participation and in-hospital security decisions on forensic decision
making. (PsycINFO Database Record
PMID- 27504643
TI - The predictive validity of the Two-Tiered Violence Risk Estimates Scale (TTV) in
a long-term follow-up of violent offenders.
AB - Over the past few decades many structured risk appraisal measures have been
created to respond to this need. The Two-Tiered Violence Risk Estimates Scale
(TTV) is a measure designed to integrate both an actuarial estimate of violence
risk with critical risk management indicators. The current study examined
interrater reliability and the predictive validity of the TTV in a sample of
violent offenders (n = 120) over an average follow-up period of 17.75 years. The
TTV was retrospectively scored and compared with the Violence Risk Appraisal
Guide (VRAG), the Statistical Information of Recidivism Scale-Revised (SIR-R1),
and the Psychopathy Checklist-Revised (PCL-R). Approximately 53% of the sample
reoffended violently, with an overall recidivism rate of 74%. Although the VRAG
was the strongest predictor of violent recidivism in the sample, the Actuarial
Risk Estimates (ARE) scale of the TTV produced a small, significant effect. The
Risk Management Indicators (RMI) produced nonsignificant area under the curve
(AUC) values for all recidivism outcomes. Comparisons between measures using AUC
values and Cox regression showed that there were no statistical differences in
predictive validity. The results of this research will be used to inform the
validation and reliability literature on the TTV, and will contribute to the
overall risk assessment literature. (PsycINFO Database Record
PMID- 27504644
TI - Specialty courts: Who's in and are they working?
AB - The effectiveness of specialty courts has been well established in the
literature; however, previous studies have not taken into account referral biases
that may exist based on offenders' race, socioeconomic status (SES), attorney
status, and so forth. The current study hypothesized that (a) Participants who
are racially diverse, of lower SES, and represented by privately retained
attorneys would be referred less frequently to specialty courts, and (b)
Participants in specialty courts would evidence reductions in missed court
appointments and failed urinary analyses (UAs) compared with peers not enrolled
in specialty courts. Participants (N = 274) were probationers who were involved
in 1 of 3 specialty court programs (i.e., drug, driving while intoxicated [DWI],
or reentry courts) or a matched sample of probationers not in specialty court
services. Results indicated that, in general and with few exceptions, specialty
courts did not have differential referral rates based on offender demographics
including race, ethnicity, SES, or attorney status (court appointed vs. privately
retained). Results examining the effectiveness of the specialty courts were
mixed. Participants in the in-prison treatment program reentry court missed a
greater proportion of scheduled court meetings than did their matched sample
counterparts; however, the other specialty court programs did not significantly
differ from their matched-sample counterparts. Participants in the DWI court had
a significantly smaller proportion of UA failures to total UAs than did their
matched sample peers; however, the drug court and reentry court programs did not
significantly differ from their matched sample counterparts. Implications, future
directions, and limitations are discussed. (PsycINFO Database Record
PMID- 27504645
TI - Recidivism risk factors are correlated with a history of psychiatric
hospitalization among sex offenders.
AB - Sexual offenders are more likely to have a history of psychiatric hospitalization
compared with the general population. This finding suggests that a history of
psychiatric hospitalization is a plausible risk factor for the initiation of
sexual crimes. It is less clear, however, whether psychiatric hospitalization is
associated with risk factors for criminal recidivism. Consequently, the current
study examined the correlates of psychiatric hospitalization and its relevance
for risk assessment in a sample of sexual offenders on community supervision (N =
947). In this sample, a history of psychiatric hospitalization significantly
increased the rate of sexual recidivism (hazard ratio = 1.95). After controlling
for well-established risk factors, however, the association was no longer
statistically significant. Consequently, this study supported an indirect effect
of a history of psychiatric hospitalization, such that the association between
psychiatric symptoms and recidivism was mediated by criminogenic needs (e.g.,
poor general self-regulation, loneliness, and social rejection). Replication
studies are needed to confirm this association, and to further understand the
link between mental illness and recidivism for sexual offenders. (PsycINFO
Database Record
PMID- 27504646
TI - Connecting the disconnected: Preliminary results and lessons learned from a
telepsychology initiative with special management inmates.
AB - The use of telepsychology, such as videoconferencing (VC) systems, has been
rapidly increasing as a tool for the provision of mental health services to
underserved clients in difficult to access settings. Inmates detained in
restrictive housing appear to be at an increased risk of experiencing emotional
and behavioral disturbances compared to their general population counterparts,
yet they are less likely to receive appropriate treatment due to security
constraints. The primary purpose of this article is to describe the process of
implementing a novel telepsychology intervention specifically designed to offer
group therapy to high-security, administratively segregated inmates. In addition,
preliminary results on treatment and therapeutic process outcomes in a sample of
49 participants are reported. Although some evidence indicated that
telepsychology was less preferred than in-person sessions, group differences on
measures of psychological functioning and criminal thinking were not found across
3 conditions (telepsychology, in-person, and a no-treatment control).
Furthermore, a number of limitations associated with program implementation and
study design suggest that results be interpreted with caution and should not be
used to discount the use of telepsychology as a viable treatment delivery option.
Recommendations for future development and evaluation of telepsychological
programs are discussed within the context of correctional settings and beyond.
(PsycINFO Database Record
PMID- 27504647
TI - Potential risks to offspring of intrauterine exposure to maternal age-related
obstetric complications.
AB - Several hypotheses have been proposed to explain the negative effects of delayed
motherhood on an offspring's morbidity later in life. However, these hypotheses
are not supported by clinical and epidemiological evidence. Because advanced
maternal age is associated with increased risk of obstetric complications, the
aim of the present study was to ascertain whether the negative effects on
offspring of intrauterine exposure to maternal age-related obstetric
complications may explain the reported negative effects of delayed motherhood on
offspring. To this end, a literature search was performed to identify relevant
publications up to March 2016 on PubMed; references cited in relevant articles
were also searched. There was a direct correlation between the risks to offspring
conferred by intrauterine exposure to at least one of the obstetric complications
present at the time of delivery in women aged >=35 years and the risks to
offspring of delayed motherhood. This correlation was not observed when comparing
the risks to offspring of delayed motherhood and the risks associated with
maternal transmission of defective mitochondria, chromosomal anomalies or DNA
double-strand breaks. Most of the effects on offspring of intrauterine exposure
to maternal age-related obstetric complications may be induced by epigenetic DNA
reprogramming during critical periods of embryo or fetal development. Women
wanting to enrol in a fertility preservation program to offset age-related
declines in fertility should be informed not only about their chances of
pregnancy and the percentage of live births, but also about the risks to
themselves and their prospective offspring of delaying motherhood.
PMID- 27504648
TI - Prophylactic Cerclage With Braided Polyblend Suture During Femoral Broaching.
AB - Femur fractures occur during broaching and impaction of the implant during hip
arthroplasty. Prophylactic cerclage of the proximal femur with braided cable and
steel wire has been shown to decrease hoop stresses and has been posited as a way
to decrease the incidence of intraoperative fracture. In this biomechanical
study, the authors investigated the strain across the proximal femur during
broaching after the application of stainless steel wire, comparing it with that
for braided polyblend suture. Nine femur models were prepared, and strain gauges
were applied to each of 3 groups. The control group received no cerclage, the
second group received a double loop of suture, and the third group received a
single loop of steel wire. A broach was firmly seated in each femur and
sequentially increasing axial loads were applied at 1000 N, 2000 N, 3000 N, 4000
N, 5000 N, and 6000 N and to failure. Strain at all loads was lower in both
cerclage groups than in the control group. Strain was 28.6%+/-12.4% lower in the
suture group than in the control group (P=.0003). Strain was 30.8%+/-10.7% lower
in the steel wire group than in the control group (P=.0011). There was no
statistically significant difference between suture cerclage and steel wire
cerclage (P=.7367). When used for prophylactic cerclage of the proximal femur,
braided polyblend suture increases hoop stress resistance, decreases strain, and
may play a clinically useful role in decreasing intraoperative proximal femur
fractures during hip arthroplasty. [Orthopedics. 2016; 39(6):e1183-e1187.].
PMID- 27504649
TI - Bone Reduction Clamp to Gain Length in Repairing Chronic Achilles Tendon
Ruptures.
AB - Chronic Achilles tendon ruptures occur after an unrecognized, untreated, or
misdiagnosed acute Achilles tendon rupture and present a potentially debilitating
injury for the patient. Various techniques have been described to reconstruct the
Achilles tendon after chronic ruptures. The technique chosen depends on the
length of tendon defect that is present after debridement. If the tendon gap is
greater than 3 cm, additional techniques are generally used, as direct repair is
often not possible. The authors present a novel intraoperative technique using
pointed reduction clamps to gain and maintain length of the Achilles tendon to
decrease the gap between ends of the Achilles tendon and allow for end-to-end
repair when it may have otherwise not been possible. [Orthopedics. 2016;
39(6):e1223-e1225.].
PMID- 27504650
TI - The Mini C-arm Adds Quality and Efficiency to the Pediatric Orthopedic Outpatient
Clinic.
AB - The mini C-arm has become increasingly popular in the practice of orthopedics. To
the authors' knowledge, its use in the pediatric orthopedic outpatient clinic has
not been reported. The purpose of this study was to evaluate the practice
efficiency and radiation exposure to the patient when the mini C-arm was used in
the pediatric orthopedic outpatient clinic. One hundred consecutive midshaft and
distal forearm fractures were evaluated by one orthopedic surgeon in follow-up
using a mini C-arm. For each case, the radiation physicist calculated the amount
of skin exposure in milligray (mGy). The average skin exposure to the patient
from the mini C-arm was 0.58 mGy, compared with 0.2 mGy for anteroposterior view
and lateral view radiographs. Use of the mini C-arm, in place of plain
radiographs obtained in the radiology department, decreased time waiting during
clinic visits by 23 minutes. This study reports 2 important findings. First,
surprisingly, the mini C-arm used a slightly higher radiation dose than standard
imaging with plain radiographs. Second, use of the mini C-arm saved time and
improved the efficiency of the clinic visit. Overall, the mini C-arm improves
quality and efficiency in the pediatric orthopedic outpatient clinic.
[Orthopedics. 2016; 39(6):e1097-e1099.].
PMID- 27504651
TI - Wear Analysis of Second-generation Highly Cross-Linked Polyethylene in Primary
Total Hip Arthroplasty.
AB - A major limiting factor in the longevity of total hip replacement is the wear
rate of the hip bearing. As manufacturing technology has improved during the past
several decades, much attention has been focused on developing newer generations
of polyethylene that have lower rates of wear while minimizing free radical
formation and subsequent osteolysis. The turning point for the manufacture of
polyethylene was moving from gamma irradiation in air to irradiation in a low
oxygen environment, which reduced free radical formation while increasing the
wear resistance. New polyethylene manufacturing methods, including multiple
cycles of irradiation and annealing, have resulted in greater wear resistance.
Wear analysis studies are essential to determine if these new liners actually
show a benefit from prior generations of polyethylene and, more importantly, if
they are safe to use. This study involved a single center retrospective review of
60 patients with a mean follow-up of 5.5 years who underwent primary total hip
arthroplasty with a second-generation highly cross-linked polyethylene
manufactured by 3 cycles of sequential irradiation and annealing. Linear and
volumetric wear rates were determined from digitized radiographs using
contemporary wear analysis software. The mean linear wear rate for the entire
group was 0.025 millimeters per year (mm/y). This value represents a linear wear
rate 2.7 times less than that of a first-generation highly cross-linked
polyethylene and 4.2 times less than that of a conventional polyethylene. At an
average of 5 years, compared with a first-generation highly cross-linked
polyethylene, a second-generation highly cross-linked polyethylene appears to
show significant improvement regarding wear. [Orthopedics. 2016; 39(6):e1178
e1182.].
PMID- 27504652
TI - The effects of proximal withdrawal states on job attitudes, job searching, intent
to leave, and employee turnover.
AB - We present the first major test of proximal withdrawal states theory (PWST; Hom,
Mitchell, Lee, & Griffeth, 2012). In addition, we develop and test new ideas to
demonstrate how PWST improves our understanding and prediction of employee
turnover. Across 2 studies, we corroborate that reluctant stayers (those who want
to leave but have to stay) are similar to enthusiastic leavers (those who want to
leave and can leave) in affective commitment, job satisfaction, and job
embeddedness, and that reluctant leavers (those who want to stay but have to
leave) are similar to enthusiastic stayers (those who want to stay and can stay)
on these dimensions. We find that job satisfaction and job embeddedness more
strongly influence the intent to leave and job search behavior for enthusiastic
stayers and leavers than for reluctant stayers and leavers. More important, we
show that for those experiencing low control over their preference for leaving or
staying (i.e., reluctant stayers and leavers), traditional variables such as job
satisfaction, job embeddedness, and intent to leave are poor predictors of their
turnover behavior. We further demonstrate that focusing on enthusiastic stayers
and leavers can significantly enhance the accuracy of job satisfaction, job
embeddedness, and intent to leave for predicting actual employee turnover.
(PsycINFO Database Record
PMID- 27504653
TI - Do it well and do it right: The impact of service climate and ethical climate on
business performance and the boundary conditions.
AB - Prior research has demonstrated that service climate can enhance unit performance
by guiding employees' service behavior to satisfy customers. Extending this
literature, we identified ethical climate toward customers as another
indispensable organizational climate in service contexts and examined how and
when service climate operates in conjunction with ethical climate to enhance
business performance of service units. Based on data collected in 2 phases over 6
months from multiple sources of 196 movie theaters, we found that service climate
and ethical climate had disparate impacts on business performance,
operationalized as an index of customer attendance rate and operating income per
labor hour, by enhancing service behavior and reducing unethical behavior,
respectively. Furthermore, we found that service behavior and unethical behavior
interacted to affect business performance, in such a way that service behavior
was more positively related to business performance when unethical behavior was
low than when it was high. This interactive effect between service and unethical
behaviors was further strengthened by high market turbulence and competitive
intensity. These findings provide new insight into theoretical development of
service management and offer practical implications about how to maximize
business performance of service units by managing organizational climates and
employee behaviors synergistically. (PsycINFO Database Record
PMID- 27504654
TI - The problem of effect size heterogeneity in meta-analytic structural equation
modeling.
AB - Scholars increasingly recognize the potential of meta-analytic structural
equation modeling (MASEM) as a way to build and test theory (Bergh et al., 2016).
Yet, 1 of the greatest challenges facing MASEM researchers is how to incorporate
and model meaningful effect size heterogeneity identified in the bivariate meta
analysis into MASEM. Unfortunately, common MASEM approaches in applied psychology
(i.e., Viswesvaran & Ones, 1995) fail to account for effect size heterogeneity.
This means that MASEM effect sizes, path estimates, and overall fit values may
only generalize to a small segment of the population. In this research, we
quantify this problem and introduce a set of techniques that retain both the true
score relationships and the variability surrounding those relationships in
estimating model parameters and fit indices. We report our findings from
simulated data as well as from a reanalysis of published MASEM studies. Results
demonstrate that both path estimates and overall model fit indices are less
representative of the population than existing MASEM research would suggest. We
suggest 2 extension MASEM techniques that can be conducted using online software
or in R, to quantify the stability of model estimates across the population and
allow researchers to better build and test theory. (PsycINFO Database Record
PMID- 27504655
TI - Are organizational justice rules gendered? Reactions to men's and women's justice
violations.
AB - Research has shown that gender role prescriptions can bias reactions to men's and
women's work behaviors. The current work draws upon this idea and extends it to
consider violations of procedural and interactional justice rules. The results of
four experimental studies demonstrate that men and women receive differential
performance evaluation ratings and reward recommendations when they violate those
organizational justice rules that coincide with the content of prescriptive
gender stereotypes. Specifically, women were rated less favorably than men when
they exhibited interactional injustice (Study 1 and Study 4), but not when they
engaged in procedural injustice (Study 2). Findings also indicate that
interactional justice violations (e.g., being impolite, not caring about the well
being of subordinates), but not procedural justice violations, are deemed less
acceptable for female managers than male managers (Study 3). Overall, the
findings suggest that reactions to injustice can be influenced by expectations of
how men and women should behave. (PsycINFO Database Record
PMID- 27504656
TI - Impressed by impression management: Newcomer reactions to ingratiated
supervisors.
AB - Organizational newcomers are unfamiliar with many aspects of their workplace and
look for information to help them reduce uncertainty and better understand their
new environment. One aspect critical to newcomers is the disposition of their
supervisor-the person who arguably can impact the newcomer's career the most. To
form an impression of their new supervisor, newcomers look to social cues from
coworkers who have interpersonal contact with the supervisor. In the present
research, we investigate the ways newcomers use observed ingratiation-a common
impression management strategy whereby coworkers try to appear likable
(Schlenker, 1980)-to form impressions of a supervisor's warmth. Research on
social influence cannot easily account for how third parties will interpret
ingratiation, as the behaviors linked to ingratiation suggest something positive
about the target, yet the unsavory aspects of the behavior imply it may not have
the same effects as other positive behaviors. Our findings suggest that newcomers
are unique in that they are motivated to learn about their new supervisor, and
are prone to ignore those unsavory aspects and infer something positive about a
supervisor targeted with ingratiation. Our findings also suggest that this effect
can be weakened based on the supervisor's response. In other words, newcomers
rely less on evidence from a coworker's ingratiation in the presence of direct
behaviors from the supervisor. (PsycINFO Database Record
PMID- 27504657
TI - Multisource feedback, human capital, and the financial performance of
organizations.
AB - We investigated the relationship between organizations' use of multisource
feedback (MSF) programs and their financial performance. We proposed a moderated
mediation framework in which the employees' ability and knowledge sharing mediate
the relationship between MSF and organizational performance and the purpose for
which MSF is used moderates the relationship of MSF with employees' ability and
knowledge sharing. With a sample of 253 organizations representing 8,879
employees from 2005 to 2007 in South Korea, we found that MSF had a positive
effect on organizational financial performance via employees' ability and
knowledge sharing. We also found that when MSF was used for dual purpose (both
administrative and developmental purposes), the relationship between MSF and
knowledge sharing was stronger, and this interaction carried through to
organizational financial performance. However, the purpose of MSF did not
moderate the relationship between MSF and employees' ability. The theoretical
relevance and practical implications of the findings are discussed. (PsycINFO
Database Record
PMID- 27504658
TI - Who strikes back? A daily investigation of when and why incivility begets
incivility.
AB - Incivility at work-low intensity deviant behaviors with an ambiguous intent to
harm-has been on the rise, yielding negative consequences for employees' well
being and companies' bottom-lines. Although examinations of incivility have
gained momentum in organizational research, theory and empirical tests involving
dynamic, within-person processes associated with this negative interpersonal
behavior are limited. Drawing from ego depletion theory, we test how experiencing
incivility precipitates instigating incivility toward others at work via reduced
self-control. Using an experience sampling design across 2 work weeks, we found
that experiencing incivility earlier in the day reduced one's levels of self
control (captured via a performance-based measure of self-control), which in turn
resulted in increased instigated incivility later in the day. Moreover,
organizational politics-a stable, environmental factor-strengthened the relation
between experienced incivility and reduced self-control, whereas construal level
a stable, personal factor-weakened the relation between reduced self-control and
instigated incivility. Combined, our results yield multiple theoretical,
empirical, and practical implications for the study of incivility at work.
(PsycINFO Database Record
PMID- 27504659
TI - Facilitating women's success in business: Interrupting the process of stereotype
threat through affirmation of personal values.
AB - Two field experiments examined if and how values affirmations can ameliorate
stereotype threat-induced gender performance gaps in an international competitive
business environment. Based on self-affirmation theory (Steele, 1988), we
predicted that writing about personal values unrelated to the perceived threat
would attenuate the gender performance gap. Study 1 found that an online
assignment to write about one's personal values (but not a similar writing
assignment including organizational values) closed the gender gap in course
grades by 89.0% among 423 Masters of Business Administration students (MBAs) at
an international business school. Study 2 replicated this effect among 396 MBAs
in a different cohort with random assignment and tested 3 related mediators (self
efficacy, self-doubt, and self-criticism). Personal values reflection (but not
reflecting on values including those of the organization or writing about others'
values) reduced the gender gap by 66.5%, and there was a significant indirect
effect through reduced self-doubt. These findings show that a brief personal
values writing exercise can dramatically improve women's performance in
competitive environments where they are negatively stereotyped. The results also
demonstrate that stereotype threat (Steele & Aronson, 1995) can occur within a
largely non-American population with work experience and that affirming one's
core personal values (without organizational values) can ameliorate the threat.
(PsycINFO Database Record
PMID- 27504660
TI - The dynamics of team cognition: A process-oriented theory of knowledge emergence
in teams.
AB - Team cognition has been identified as a critical component of team performance
and decision-making. However, theory and research in this domain continues to
remain largely static; articulation and examination of the dynamic processes
through which collectively held knowledge emerges from the individual- to the
team-level is lacking. To address this gap, we advance and systematically
evaluate a process-oriented theory of team knowledge emergence. First, we
summarize the core concepts and dynamic mechanisms that underlie team knowledge
building and represent our theory of team knowledge emergence (Step 1). We then
translate this narrative theory into a formal computational model that provides
an explicit specification of how these core concepts and mechanisms interact to
produce emergent team knowledge (Step 2). The computational model is next
instantiated into an agent-based simulation to explore how the key generative
process mechanisms described in our theory contribute to improved knowledge
emergence in teams (Step 3). Results from the simulations demonstrate that agent
teams generate collectively shared knowledge more effectively when members are
capable of processing information more efficiently and when teams follow
communication strategies that promote equal rates of information sharing across
members. Lastly, we conduct an empirical experiment with real teams participating
in a collective knowledge-building task to verify that promoting these processes
in human teams also leads to improved team knowledge emergence (Step 4).
Discussion focuses on implications of the theory for examining team cognition
processes and dynamics as well as directions for future research. (PsycINFO
Database Record
PMID- 27504661
TI - Are genetic and environmental influences on job satisfaction stable over time? A
three-wave longitudinal twin study.
AB - Job satisfaction research has unfolded as an exemplary manifestation of the
"person versus environment" debate in applied psychology. With the increasing
recognition of the importance of time, it is informative to examine a question
critical to the dispositional view of job satisfaction: Are genetic influences on
job satisfaction stable across different time points? Drawing upon dispositional
and situational perspectives on job satisfaction and recent research in
developmental behavioral genetics, we examined whether the relative potency of
genetic (i.e., the person) and environmental influences on job satisfaction
changed over time in a 3-wave longitudinal twin study. Biometric behavioral
genetics analyses showed that genetic influences accounted for 31.2% of the
variance in job satisfaction measured at approximately Age 21, which was markedly
greater than the 18.7% and 19.8% of variance explained by genetic factors at Age
25 and Age 30. Such genetic influences were mediated via positive affectivity and
negative affectivity, but not via general mental ability. After partialing out
genetic influences, environmental influences on job satisfaction were related to
interpersonal conflict at work and occupational status, and these influences were
relatively stable across the 3 time points. These results offer important
implications for organizations and employees to better understand and implement
practices to enhance job satisfaction. (PsycINFO Database Record
PMID- 27504662
TI - Fit and frustration as drivers of targeted counterproductive work behaviors: A
multifoci perspective.
AB - In this article, the authors integrate the theory of work adjustment (Dawis,
England, & Lofquist, 1964) and the stressor emotion model of counterproductive
work behaviors (CWBs; Spector & Fox, 2005) to examine workplace frustration as an
intervening mechanism that mediates relations between person-environment (P-E)
fit and CWBs. Moreover, we adopt a multifoci perspective to estimate effects for
multiple fit, frustration, and CWB foci. We examine the nature of relations
between fit, frustration, and CWB for like foci (target similar effects), as well
as cross-foci effects. Study 1 examines proposed effects in a sample of 447
employee-coworker dyads. Study 2 uses a 3-wave survey design and tests effects in
a sample of 669 employees. Results from both studies suggest that (a) frustration
mediates the effects of P-E fit on CWBs and (b) the most consistent effects were
observed among the variables with matching foci. Implications for research and
practice are discussed. (PsycINFO Database Record
PMID- 27504663
TI - When do high-context communicators speak up? Exploring contextual communication
orientation and employee voice.
AB - Past research suggests that individuals oriented toward high-context
communication are less likely than are others to voice (i.e., speak up) at work.
In the current article, we rely on high-/low-context theory to explore potential
boundary conditions of this relationship. We conducted 2 studies exploring the
relationship between contextual communication orientation and 2 distinct types of
voice (prohibitive and promotive). As hypothesized, both studies showed that the
negative relationship between contextual communication orientation and voice was
weaker for prohibitive (compared with promotive) voice. Results of Study 1 showed
that, as hypothesized, leader-member exchange (LMX) moderated the relationship
between contextual communication orientation and promotive voice, such that the
relationship was negative when LMX was low but not significant when high. The
interaction was not significant in predicting prohibitive voice in Study 1 or in
predicting either voice type in Study 2. (PsycINFO Database Record
PMID- 27504664
TI - "Demographic faultlines: A meta-analysis of the literature": Retraction of
Thatcher and Patel (2011).
AB - Reports the retraction of "Demographic faultlines: A meta-analysis of the
literature" by Sherry M. B. Thatcher and Pankaj C. Patel (Journal of Applied
Psychology, 2011[Nov], Vol 96[6], 1119-1139). At the request of the editor and in
consultation with the American Psychological Association, the article is being
retracted. This action is a result of a review by the editor and two additional
experts that determined that there are significant errors in Tables 1, 2, and 3
which may affect the overall conclusions of the article. Co-author Pankaj C.
Patel led the analysis, and both authors acknowledge that inaccuracies were made.
The retraction of this article does not preclude resubmission of a new article
that addresses the issues noted in the retraction. (The following abstract of the
original article appeared in record 2011-12686-001.) We propose and test a
theoretical model focusing on antecedents and consequences of demographic
faultlines. We also posit contingencies that affect overall team dynamics in the
context of demographic faultlines, such as the study setting and performance
measurement. Using meta-analysis structural equation modeling with a final data
set consisting of 311 data points (i.e., k [predictor-criterion relationships]),
from 39 studies that were obtained from 36 papers with a total sample size of
24,388 individuals in 4,366 teams, we found that sex and racial diversity
increased demographic faultline strength more than did diversity on the
attributes of functional background, educational background, age, and tenure.
Demographic faultline strength was found to increase task and relationship
conflict as well as decrease team cohesion. Furthermore, although demographic
faultline strength decreased both team satisfaction and team performance, there
was a stronger decrease in team performance than in team satisfaction. The
strength of these relationships increased when the study was conducted in the lab
rather than in the field. We describe the theoretical and practical implications
of these findings for advancing the study of faultlines.
PMID- 27504665
TI - In Vitro Evaluation of CRISPR/Cas9 Function by an Electrochemiluminescent Assay.
AB - The CRISPR/Cas9 system is a revolutionary genome-editing tool that enables
targeted and efficient gene knockouts. However, the off-target effects and loci
dependent enzyme activity limit its uses on the field of research and treatment.
In this study, we designed a convenient and sensitive in vitro test method, which
was based on electrochemiluminescence (ECL) technology for evaluating cleavage
activity of the CRISPR/Cas9 system. It was find that Cas9 can tolerate some
common genetic modifications to its target DNA. It was also find that target
DNA/sgRNA with single-base mismatch and UV damages of target DNA resulted in
significantly reduction of Cas9 cleavage efficiency. Comparing with traditional
method, the proposed method reduced the evaluation time from weeks to 2 h.
Therefore, our study provides a versatile in vitro method for a priori analysis
of CRISPR/Cas9 system and highlights the potential to guide in vivo genome
editing.
PMID- 27504666
TI - Dimensionless Equation of State to Predict Microemulsion Phase Behavior.
AB - Prediction of microemulsion phase behavior for changing state variables is
critical to formulation design of surfactant-oil-brine (SOB) systems. SOB systems
find applications in various chemical and petroleum processes, including enhanced
oil recovery. A dimensional equation-of-state (EoS) was recently presented by
Ghosh and Johns1 that relied on estimation of the surfactant tail length and
surface area. We give an algorithm for flash calculations for estimation of three
phase Winsor regions that is more robust, simpler, and noniterative by making the
equations dimensionless so that estimates of tail length and surface area are no
longer needed. We predict phase behavior as a function temperature, pressure,
volume, salinity, oil type, oil-water ratio, and surfactant/alcohol
concentration. The dimensionless EoS is based on coupling the HLD-NAC
(Hydrophilic Lipophilic Difference-Net Average Curvature) equations with new
relationships between optimum salinity and solubility. An updated HLD expression
that includes pressure is also used to complete the state description. A
significant advantage of the dimensionless form of the EoS over the dimensional
version is that salinity scans are tuned based only on one parameter, the
interfacial volume ratio. Further, stability conditions are developed in a
simplified way to predict whether an overall compositions lies within the single,
two-, or three-phase regions. Important new microemulsion relationships are also
found, the most important of which is that optimum solubilization ratio is equal
to the harmonic mean of the oil and water solubilization ratios in the type III
region. Thus, only one experimental measurement is needed in the three-phase zone
to estimate the optimum solubilization ratio, a result which can aid experimental
design and improve estimates of optimum from noisy data. Predictions with
changing state variables are illustrated by comparison to experimental data using
standard diagrams including a new type of dimensionless fish plot. The results
show that the optimum solubilization ratio and salinity using the tuned
dimensionless EoS are within average errors of 2.44% and 1.17% of experimental
values for the fluids examined. We then use the dimensionless equations and
thermodynamic first-principles to derive the constant in Huh's equation for
interfacial tension prediction.
PMID- 27504667
TI - Application of Coiled Coil Peptides in Liposomal Anticancer Drug Delivery Using a
Zebrafish Xenograft Model.
AB - The complementary coiled coil forming peptides E4 [(EIAALEK)4] and K4
[(KIAALKE)4] are known to trigger liposomal membrane fusion when tethered to
lipid vesicles in the form of lipopeptides. In this study, we examined whether
these coiled coil forming peptides can be used for drug delivery applications.
First, we prepared E4 peptide modified liposomes containing the far-red
fluorescent dye TO-PRO-3 iodide (E4-Lipo-TP3) and confirmed that E4-liposomes
could deliver TP3 into HeLa cells expressing K4 peptide on the membrane (HeLa-K)
under cell culture conditions in a selective manner. Next, we prepared
doxorubicin-containing E4-liposomes (E4-Lipo-DOX) and confirmed that E4-liposomes
could also deliver DOX into HeLa-K cells. Moreover, E4-Lipo-DOX showed enhanced
cytotoxicity toward HeLa-K cells compared to free doxorubicin. To prove the
suitability of E4/K4 coiled coil formation for in vivo drug delivery, we injected
E4-Lipo-TP3 or E4-Lipo-DOX into zebrafish xenografts of HeLa-K. As a result, E4
liposomes delivered TP3 to the implanted HeLa-K cells, and E4-Lipo-DOX could
suppress cancer proliferation in the xenograft when compared to nontargeted
conditions (i.e., zebrafish xenograft with free DOX injection). These data
demonstrate that coiled coil formation enables drug selectivity and efficacy in
vivo. It is envisaged that these findings are a step forward toward biorthogonal
targeting systems as a tool for clinical drug delivery.
PMID- 27504668
TI - Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome
Associated Proteins.
AB - During mitosis, phosphorylation of chromosome-associated proteins is a key
regulatory mechanism. Mass spectrometry has been successfully applied to
determine the complete protein composition of mitotic chromosomes, but not to
identify post-translational modifications. Here, we quantitatively compared the
phosphoproteome of isolated mitotic chromosomes with that of chromosomes in
nonsynchronized cells. We identified 4274 total phosphorylation sites and 350
mitosis-specific phosphorylation sites in mitotic chromosome-associated proteins.
Significant mitosis-specific phosphorylation in centromere/kinetochore proteins
was detected, although the chromosomal association of these proteins did not
change throughout the cell cycle. This mitosis-specific phosphorylation might
play a key role in regulation of mitosis. Further analysis revealed strong
dependency of phosphorylation dynamics on kinase consensus patterns, thus linking
the identified phosphorylation sites to known key mitotic kinases. Remarkably,
chromosomal axial proteins such as non-SMC subunits of condensin, TopoIIalpha,
and Kif4A, together with the chromosomal periphery protein Ki67 involved in the
establishment of the mitotic chromosomal structure, demonstrated high
phosphorylation during mitosis. These findings suggest a novel mechanism for
regulation of chromosome restructuring in mitosis via protein phosphorylation.
Our study generated a large quantitative database on protein phosphorylation in
mitotic and nonmitotic chromosomes, thus providing insights into the dynamics of
chromatin protein phosphorylation at mitosis onset.
PMID- 27504669
TI - Hernandezine, a Bisbenzylisoquinoline Alkaloid with Selective Inhibitory Activity
against Multidrug-Resistance-Linked ATP-Binding Cassette Drug Transporter ABCB1.
AB - The overexpression of ATP-binding cassette (ABC) drug transporter ABCB1 (P
glycoprotein, MDR1) is the most studied mechanism of multidrug resistance (MDR),
which remains a major obstacle in clinical cancer chemotherapy. Consequently,
resensitizing MDR cancer cells by inhibiting the efflux function of ABCB1 has
been considered as a potential strategy to overcome ABCB1-mediated MDR in cancer
patients. However, the task of developing a suitable modulator of ABCB1 has been
hindered mostly by the lack of selectivity and high intrinsic toxicity of
candidate compounds. Considering the wide range of diversity and relatively
nontoxic nature of natural products, developing a potential modulator of ABCB1
from natural sources is particularly valuable. Through screening of a large
collection of purified bioactive natural products, hernandezine was identified as
a potent and selective reversing agent for ABCB1-mediated MDR in cancer cells.
Experimental data demonstrated that the bisbenzylisoquinoline alkaloid
hernandezine is selective for ABCB1, effectively inhibits the transport function
of ABCB1, and enhances drug-induced apoptosis in cancer cells. More importantly,
hernandezine significantly resensitizes ABCB1-overexpressing cancer cells to
multiple chemotherapeutic drugs at nontoxic, nanomolar concentrations.
Collectively, these findings reveal that hernandezine has great potential to be
further developed into a novel reversal agent for combination therapy in MDR
cancer patients.
PMID- 27504670
TI - Microglia-Based Phenotypic Screening Identifies a Novel Inhibitor of
Neuroinflammation Effective in Alzheimer's Disease Models.
AB - Currently, anti-AD drug discovery using target-based approaches is extremely
challenging due to unclear etiology of AD and absence of validated therapeutic
protein targets. Neuronal death, regardless of causes, plays a key role in AD
progression, and it is directly linked to neuroinflammation. Meanwhile,
phenotypic screening is making a resurgence in drug discovery process as an
alternative to target-focused approaches. Herein, we employed microglia-based
phenotypic screenings to search for small molecules that modulate the release of
detrimental proinflammatory cytokines. The identified novel pharmacological
inhibitor of neuroinflammation (named GIBH-130) was validated to alter phenotypes
of neuroinflammation in AD brains. Notably, this molecule exhibited comparable in
vivo efficacy of cognitive impairment relief to donepezil and memantine
respectively in both beta amyloid-induced and APP/PS1 double transgenic
Alzheimer's murine models at a substantially lower dose (0.25 mg/kg). Therefore,
GIBH-130 constitutes a unique chemical probe for pathogenesis research and drug
development of AD, and it also suggests microglia-based phenotypic screenings
that target neuroinflammation as an effective and feasible strategy to identify
novel anti-AD agents.
PMID- 27504671
TI - Copper-Catalyzed Intramolecular Benzylic C-H Amination for the Synthesis of
Isoindolinones.
AB - A copper-catalyzed intramolecular amination occurs at the benzylic C-H of 2
methylbenzamides to deliver the corresponding isoindolinones of great interest in
medicinal chemistry. The mild and abundant MnO2 works well as a terminal oxidant,
and the reaction proceeds smoothly under potentially explosive organic peroxide
free conditions. Additionally, the directing-group-dependent divergent mechanisms
are proposed: 8-aminoquinoline-containing benzamides include a Cu-mediated
organometallic pathway whereas an aminyl radical-promoted Hofmann-Loffler-Freytag
(HLF)-type mechanism can be operative in the case of N-naphthyl-substituted
substrates.
PMID- 27504672
TI - How Do Distance and Solvent Affect Halogen Bonding Involving Negatively Charged
Donors?
AB - It was reported that negatively charged donors can form halogen bonding, which is
stable, especially, in a polar environment. On the basis of a survey of the
Protein Data Bank, we noticed that the distance between the negative charge
center and the halogen atom of an organohalogen may vary greatly. Therefore, a
series of model systems, composed of 4-halophenyl-conjugated polyene acids and
ammonia, were designed to explore the potential effect of distance on halogen
bonding in different solvents. Quantum mechanics (QM) calculations demonstrated
that the longer the distance, the stronger the bonding. The energy decomposition
analysis on all of the model systems demonstrated that electrostatic interaction
contributes the most (44-56%) to the overall binding, followed by orbital
interaction (42-36%). Natural bond orbital calculations showed that electron
transfer takes place from the acceptor to the donor, whereas the halogen atom
becomes more positive during the bonding, which is in agreement with the result
of neutral halogen bonding. QM/molecular mechanics calculations demonstrated that
the polarity of binding pockets makes all of the interactions attractive in a
protein system. Hence, the strength of halogen bonding involving negatively
charged donors could be adjusted by changing the distance between the negative
charge center and halogen atom and the environment in which the bonding exists,
which may be applied in material and drug design for tuning their function and
activity.
PMID- 27504673
TI - Dispersed Fluorescence Spectroscopy of Jet-Cooled Isobutoxy and 2-Methyl-1-butoxy
Radicals.
AB - We report dispersed fluorescence (DF) spectra of the isobutoxy and 2-methyl-1
butoxy radicals produced by photolysis of corresponding nitrites in supersonic
jet expansion. Different vibrational structures have been observed in the DF
spectra when different vibronic bands in the laser-induced fluorescence (LIF)
spectra of each radical were pumped, which suggests that those vibronic bands be
assigned to different conformers. Spectra simulated using calculated vibrational
frequencies and Franck-Condon factors well reproduce the experimentally observed
ones and support the assignment of the vibronic bands in the LIF spectra to the
two lowest-energy conformers of each radical. DF spectra obtained by pumping the
B <- X origin bands of the LIF spectra are dominated by CO stretch progressions
because of the large difference in CO bond length between the ground (X) and the
second excited (B) electronic states. Furthermore, with non-CO stretch bands
pumped, the DF spectra are dominated by progressions of combination bands of the
CO stretch and the pumped modes as a result of Duschinsky mixing. A-X separation
of both conformers of the isobutoxy radical has also been determined in the
experiment.
PMID- 27504674
TI - K3B3O4(OH)4.2H2O: A UV Nonlinear Optical Crystal with Isolated [B3O4(OH)4](3-)
Anion Groups.
AB - A potential ultraviolet (UV) nonlinear optical (NLO) material, K3B3O4(OH)4.2H2O,
was successfully synthesized by hydrothermal methods. The compound crystallizes
into the Cmc21 space group and exhibits isolated [B3O4(OH)4](3-) anion groups
connected by O-H...O hydrogen bonds. The UV-vis diffuse reflectance spectrum
shows that K3B3O4(OH)4.2H2O has a wide transparency range with an absorption edge
below 190 nm. Powder second harmonic generation (SHG) measurements using 1064 nm
radiation revealed a moderate efficiency, 0.8 * KDP. Additional particle size vs
SHG efficiency measurements indicate that K3B3O4(OH)4.2H2O is type I phase
matchable. Our calculated results show that the borate groups as well as the
waters of hydration determine the NLO properties of K3B3O4(OH)4.2H2O.
PMID- 27504675
TI - Toward Lower Overpotential through Improved Electron Transport Property:
Hierarchically Porous CoN Nanorods Prepared by Nitridation for Lithium-Oxygen
Batteries.
AB - To lower the overpotential of a lithium-oxygen battery, electron transport at the
solid-to-solid interface between the discharge product Li2O2 and the cathode
catalyst is of great significance. Here we propose a strategy to enhance electron
transport property of the cathode catalyst by the replace of oxygen atoms in the
generally used metal oxide-based catalysts with nitrogen atoms to improve
electron density at Fermi energy after nitridation. Hierarchically porous CoN
nanorods were obtained by thermal treatment of Co3O4 nanorods under ammonia
atmosphere at 350 degrees C. Compared with that of the pristine Co3O4 precursor
before nitridation, the overpotential of the obtained CoN cathode was
significantly decreased. Moreover, specific capacity and cycling stability of the
CoN nanorods were enhanced. It is assumed that the discharged products with
different morphologies for Co3O4 and CoN cathodes might be closely associated
with the variation in the electronic density induced by occupancy of nitrogen
atoms into interstitial sites of metal lattice after nitridation. The nitridation
strategy for improved electron density proposed in this work is proved to be a
simple but efficient way to improve the electrochemical performance of metal
oxide based cathodes for lithium-oxygen batteries.
PMID- 27504676
TI - Clinician's Commentary on Chan et al.(1).
PMID- 27504677
TI - An eye-tracking investigation of written sarcasm comprehension: The roles of
familiarity and context.
AB - This article addresses a current theoretical debate between the standard
pragmatic model, the graded salience hypothesis, and the implicit display theory,
by investigating the roles of the context and of the properties of the sarcastic
utterance itself in the comprehension of a sarcastic remark. Two eye-tracking
experiments were conducted where we manipulated the speaker's expectation in the
context and the familiarity of the sarcastic remark. The results of the first eye
tracking study showed that literal comments were read faster than unfamiliar
sarcastic comments, regardless of whether an explicit expectation was present in
the context. The results of the second eye-tracking study indicated an early
processing difficulty for unfamiliar sarcastic comments, but not for familiar
sarcastic comments. Later reading time measures indicated a general difficulty
for sarcastic comments. Overall, results seem to suggest that the familiarity of
the utterance does indeed affect the time course of sarcasm processing
(supporting the graded salience hypothesis), although there is no evidence that
making the speaker's expectation explicit in the context affects it as well (thus
failing to support the implicit display theory). (PsycINFO Database Record
PMID- 27504678
TI - Benchmark eye movement effects during natural reading in autism spectrum
disorder.
AB - In 2 experiments, eye tracking methodology was used to assess on-line lexical,
syntactic and semantic processing in autism spectrum disorder (ASD). In
Experiment 1, lexical identification was examined by manipulating the frequency
of target words. Both typically developed (TD) and ASD readers showed normal
frequency effects, suggesting that the processes TD and ASD readers engage in to
identify words are comparable. In Experiment 2, syntactic parsing and semantic
interpretation requiring the on-line use of world knowledge were examined, by
having participants read garden path sentences containing an ambiguous
prepositional phrase. Both groups showed normal garden path effects when reading
low-attached sentences and the time course of reading disruption was comparable
between groups. This suggests that not only do ASD readers hold similar syntactic
preferences to TD readers, but also that they use world knowledge on-line during
reading. Together, these experiments demonstrate that the initial construction of
sentence interpretation appears to be intact in ASD. However, the finding that
ASD readers skip target words less often in Experiment 2, and take longer to read
sentences during second pass for both experiments, suggests that they adopt a
more cautious reading strategy and take longer to evaluate their sentence
interpretation prior to making a manual response. (PsycINFO Database Record
PMID- 27504679
TI - Prospective memory in context: Moving through a familiar space.
AB - Successful completion of delayed intentions is a common but important aspect of
daily behavior. Such behavior requires not only memory for the intended action
but also recognition of the opportunity to perform that action, known
collectively as prospective memory. The fact that prospective memory tasks occur
in the midst of other activities is captured in laboratory tasks by embedding the
prospective memory task in an ongoing activity. In many cases the requirement to
perform the prospective memory task results in a reduction in ongoing performance
relative to when the ongoing task is performed alone. This is referred to as the
cost to the ongoing task and reflects the allocation of attentional resources to
the prospective memory task. The current study examined the pattern of cost
across the ongoing task when the ongoing task provided contextual information
that in turn allowed participants to anticipate when target events would occur
within the ongoing task. The availability of contextual information reduced
ongoing task response times overall, with an increase in response times closer to
the target locations (Experiments 1-3). The fourth study, drawing on the Event
Segmentation Theory, provided support for the proposal made by the Preparatory
Attentional and Memory Processes theory of prospective memory that decisions
about the allocation of attention to the prospective memory task are more likely
to be made at points of transition. (PsycINFO Database Record
PMID- 27504680
TI - Is it all task-specific? The role of binary responses, verbal mediation, and
saliency for eliciting language-space associations.
AB - Associations between language and space are of central interest for grounded
models of language comprehension. Various studies show that reading words such as
bird or shoe results in faster responses toward the typical location of the
corresponding entity (e.g., after bird, upward responses are faster than downward
responses). Critically, as of yet, the mechanisms underlying these effects and
their boundary conditions are widely unknown. In fact, it cannot be ruled out
that these effects are by-products of processing that only occur in very specific
task settings. Here we investigated the role of 3 major processes (response set,
labeling, and saliency) that might underlie these compatibility effects in Stroop
like paradigms. In Experiment 1, we aimed at overcoming the binary nature of the
response set by including responses both in the vertical and the horizontal
dimension. In Experiment 2 no memorizing of the color-to-response mapping was
required, making internal response labeling unnecessary. In Experiment 3 this was
replicated in a mouse-tracking setup. In all experiments a clear language-space
association was observed. Critically, in a final experiment not only the saliency
of verticality in the response set but also in the stimulus set was reduced. Here
no language-space association was observed. Together these results suggest that
language-space associations extend beyond bipolar response settings and that
internal response labeling is not a precondition for finding these compatibility
effects. However, the vertical dimension needs to be salient either in the
stimulus or response set. Implications for models of language comprehension are
discussed. (PsycINFO Database Record
PMID- 27504681
TI - Out of place, out of mind: Schema-driven false memory effects for object-location
bindings.
AB - Events consist of diverse elements, each processed in specialized neocortical
networks, with temporal lobe memory systems binding these elements to form
coherent event memories. We provide a novel theoretical analysis of an unexplored
consequence of the independence of memory systems for elements and their
bindings, 1 that raises the paradoxical prediction that schema-driven false
memories can act solely on the binding of event elements despite the superior
retrieval of individual elements. This is because if 2, or more, schema-relevant
elements are bound together in unexpected conjunctions, the unexpected
conjunction will increase attention during encoding to both the elements and
their bindings, but only the bindings will receive competition with evoked schema
expected bindings. We test our model by examining memory for object-location
bindings in recognition (Study 1) and recall (Studies 2 and 3) tasks. After
studying schema-relevant objects in unexpected locations (e.g., pan on a stool in
a kitchen scene), participants who then viewed these objects in expected
locations (e.g., pan on stove) at test were more likely to falsely remember this
object-location pairing as correct, compared with participants that viewed a
different unexpected object-location pairing (e.g., pan on floor). In recall,
participants were more likely to correctly remember individual schema-relevant
objects originally viewed in unexpected, as opposed to expected locations, but
were then more likely to misplace these items in the original room scene to
expected places, relative to control schema-irrelevant objects. Our theoretical
analysis and novel paradigm provide a tool for investigating memory distortions
acting on binding processes. (PsycINFO Database Record
PMID- 27504682
TI - Chinese readers can perceive a word even when it's composed of noncontiguous
characters.
AB - This study explored whether readers could recognize a word composed of
noncontiguous characters (a cross-character word) in Chinese reading. All 3
experiments employed Chinese 4-character strings ABCD, where both AB and CD were
2-character words. In the cross-character word condition, AC was a word but in
the control condition, AC was not a word. A character identification task was
employed in Experiment 1 and sentence reading tasks were employed in Experiments
2 and 3. In all 3 experiments, an AC word produced inhibition effects. In
Experiment 1, an AC word decreased the accuracy of character B identification,
but increased the accuracy of character C identification. In Experiments 2 and 3,
an AC word slowed reading on CD, indicating that the cross-character words were
activated. These results imply that Chinese character encoding leading to word
recognition does not proceed in a strictly serial way from left to right, or is
strictly constrained by invisible word boundaries. (PsycINFO Database Record
PMID- 27504683
TI - Morphine-Modified Hepatobiliary Scanning Protocol for the Diagnosis of Acute
Cholecystitis.
AB - OBJECTIVE: We report a morphine-modified hepatoiminodiacetic acid (HIDA) scanning
protocol that uses 2 mg of morphine IV push at the bedside as a pretreatment. We
compared this protocol with the original HIDA scanning protocol, which included
delayed imaging for up to 4 hours without the use of morphine. Moreover, we
contrast our results with the results of studies in the literature. MATERIALS AND
METHODS: We retrospectively reviewed the charts of inpatients who underwent HIDA
scanning for the diagnosis of acute cholecystitis between 2003 and 2013. The
study group consisted of 374 HIDA studies of 365 patients who received 2 mg of
morphine IV push at bedside and then underwent dynamic imaging for 1 hour using
222 MBq of 99mTc-mebrofenin. No delayed images were obtained. The control group
consisted of 232 studies of 227 patients who underwent conventional HIDA scanning
using our standard protocol with delayed imaging and without morphine. Either
strict pathologic criteria or the results of a percutaneous gallbladder drainage
procedure were used for the confirmation of acute cholecystitis. RESULTS: The
true-negative rate in the study group was 77% and in the control group, 72%. The
positive predictive value in the study group was 81% and in the control group,
45%. The negative predictive value in the study group was 98% and in the control
group, 99%. The accuracy in the study group was 95% and in the control group,
84%. The sensitivity in the study group was 93% and in the control group, 93%.
The specificity in the study group was 95% and in the control group, 83%. The
differences in the true-negative rate, accuracy, specificity, and positive
predictive value of the morphine-modified protocol used for the study group and
the original protocol used for the control group were statistically significant
(p < 0.0005). CONCLUSION: Pretreatment using 2 mg of IV morphine at bedside
before radionuclide imaging is superior to routine HIDA scanning with only
delayed images for the diagnosis of acute cholecystitis. The results of our
pretreatment morphine-modified protocol are comparable to those reported in the
literature for posttreatment morphine-augmented protocols.
PMID- 27504684
TI - Feasibility of free-breathing dynamic contrast-enhanced MRI of the abdomen: a
comparison between CAIPIRINHA-VIBE, Radial-VIBE with KWIC reconstruction and
conventional VIBE.
AB - OBJECTIVE: To evaluate the feasibilities of controlled aliasing in parallel
imaging results in higher acceleration with volumetric interpolated breath-hold
examination (CAIPIRINHA-VIBE), radial acquisition of VIBE (Radial-VIBE) with k
space-weighted image contrast (KWIC) reconstruction (KWIC-Radial-VIBE) and
conventional-VIBE (c-VIBE) for free-breathing dynamic contrast-enhanced (DCE)-MRI
of the abdomen. METHODS: 23 prospectively enrolled patients underwent DCE-MRI of
the abdomen with CAIPIRINHA-VIBE (n = 10), KWIC-Radial-VIBE (n = 6) or c-VIBE (n
= 7). Qualitative image quality of the DCE-MR images and perfusion maps was
independently scored by two abdominal radiologists using a 5-point scale (from 1,
uninterpretable, to 5, very good). For quantitative analysis, the signal-to-noise
ratio (SNR) of the liver and goodness-of-fit (GOF) of the time-intensity curve
were measured. RESULTS: In the three tested sequences, DCE-MRI had good temporal
(5 s) and spatial resolution (1.48 * 1.48 * 4 mm/voxel). Interobserver agreement
in the qualitative analysis was good (K = 0.753; 95% confidence interval, 0.610
0.895). Therefore, the mean scores were used in the data analysis. Overall image
quality was comparable between CAIPIRINHA-VIBE (3.52 +/- 0.55) and KWIC-Radial
VIBE (3.72 +/- 0.37; p = 1.000), and both were significantly better than c-VIBE
(2.71 +/- 0.34; p < 0.001). Perfusion map quality score was highest with KWIC
Radial-VIBE (4.33 +/- 0.65), followed by CAIPIRINHA-VIBE (3.70 +/- 0.73) and c
VIBE (3.14 +/- 0.66), but without statistical significance between CAIPIRINHA
VIBE and KWIC-Radial-VIBE (p = 0.167). The SNR of the liver and GOF of the time
intensity curve did not significantly differ between the three sequences (p =
0.116 and 0.224, respectively). CONCLUSION: CAIPIRINHA-VIBE and KWIC-Radial-VIBE
provide comparably better performance than c-VIBE. Both can be feasible sequences
with acceptable good image quality for free-breathing DCE-MRI. ADVANCES IN
KNOWLEDGE: CAIPIRINHA-VIBE and KWIC-Radial-VIBE provide comparably better quality
of free-breathing DCE-MRIs than c-VIBE.
PMID- 27504685
TI - Introduction of President Mark E. Siddall.
PMID- 27504686
TI - Electrochemical sensing of bisphenol using a multilayer graphene nanobelt
modified photolithography patterned platinum electrode.
AB - An electrochemical sensor has been developed for the detection of Bisphenol-A
(BPA) using photolithographically patterned platinum electrodes modified with
multilayer graphene nanobelts (GNB). Compared to bare electrodes, the GNB
modified electrode exhibited enhanced BPA oxidation current, due to the high
effective surface area and high adsorption capacity of the GNB. The sensor showed
a linear response over the concentration range from 0.5 MUM-9 MUM with a very low
limit of detection = 37.33 nM. In addition, the sensor showed very good stability
and reproducibility with good specificity, demonstrating that GNB is potentially
a new material for the development of a practical BPA electrochemical sensor with
application in both industrial and plastic industries.
PMID- 27504687
TI - Editorial: Indicators of OTJR's Growth and Success.
PMID- 27504688
TI - Caregivers' Impressions Predicting Fitness to Drive in Persons With Parkinson's.
AB - Parkinson's disease (PD) is a common neurodegenerative disease, increasing in
incidence, with a known impact on fitness to drive. Although great progress has
been made on evidence-based guidelines for assessing fitness to drive of persons
with PD, a need remains for early identification of at-risk drivers in need of
comprehensive assessment. This study investigated whether caregivers of drivers
with PD could predict the driver's on-road outcome. We also investigated whether
the predictive value of their impressions differed from that of drivers
themselves, their neurologist, or from information provided by standardized
measures of visual and divided attention. Caregivers' risk impressions (odds
ratio [OR] = 13.76, p = .03) and Trail Making Test Part B (Trails B; OR = 0.41, p
= .02) emerged as significant predictors of passing an on-road assessment. Our
findings suggest that caregiver impressions, with a measure of set shifting, may
be used as an efficient screen to identify drivers with PD who are potentially at
risk for failing an on-road assessment.
PMID- 27504689
TI - Quality and Reporting of Cluster Randomized Controlled Trials Evaluating
Occupational Therapy Interventions: A Systematic Review.
AB - Growing use of cluster randomized control trials (RCTs) in health care research
requires careful attention to study designs, with implications for the
development of an evidence base for practice. The objective of this study is to
investigate the characteristics, quality, and reporting of cluster RCTs
evaluating occupational therapy interventions to inform future research design.
An extensive search of cluster RCTs evaluating occupational therapy was conducted
in several databases. Fourteen studies met our inclusion criteria; four were
protocols. Eleven (79%) justified the use of a cluster RCT and accounted for
clustering in the sample size and analysis. All full studies reported the number
of clusters randomized, and five reported intercluster correlation coefficients
(50%): Protocols had higher compliance. Risk of bias was most evident in
unblinding of participants. Statistician involvement was associated with improved
trial quality and reporting. Quality of cluster RCTs of occupational therapy
interventions is comparable with those from other areas of health research and
needs improvement.
PMID- 27504690
TI - Understanding Family Interaction Patterns in Families With Alzheimer's Disease.
AB - This qualitative study explores the dynamic changes that occur in family
interaction patterns when Alzheimer's disease is present. Semi-structured
interviews were conducted with 15 participants who have a family member with the
disease. Using modified analytic induction, guided by the dimensions of the
Family Fundamental Interpersonal Relations Orientation (FIRO) Model, participants
shared how Alzheimer's disease affected family structure, control dynamics, and
intimacy among family members. Findings demonstrate that (a) families reorganize
and restructure based on geographic proximity and shifting roles, act out of
filial responsibility, and strive to preserve shared meanings and rituals; (b)
decision making increases around care of the person with Alzheimer's disease and
shifts to the primary caregiver or other family members based on their abilities;
and (c) expressions of intimacy intensify while personality is preserved in the
person with the disease. The Family FIRO model can inform practitioners using
family-centered care with families with Alzheimer's disease.
PMID- 27504691
TI - Non-Pharmacological Approaches to Reducing Negative Behavioral Symptoms: A
Scoping Review.
AB - The management of negative behavioral symptoms among residents with dementia is a
challenge that nursing homes face in delivering quality care. This study examines
evidence documenting non-pharmacological interventions that reduce negative
behavioral symptoms among nursing home residents with dementia and the role
occupational therapy practitioners have in this area. A scoping review was
completed for intervention studies published from 1987 to 2014, targeting
negative behavioral symptoms among nursing home residents above 60 years of age
with dementia. Interventions were categorized based on the American Occupational
Therapy Association (AOTA) Occupational Therapy Practice Framework. Twenty-two
studies met the inclusion criteria. Four types of interventions were identified:
occupation-based interventions, context and environment interventions, exercise
interventions, and daily routine-based interventions. The non-pharmacological
interventions were found to align with the scope of occupational therapy. This
suggests that occupational therapy practitioners can contribute to the
development and evaluation of non-pharmacological interventions aimed to reduce
negative behavioral symptoms.
PMID- 27504693
TI - Acid-Catalyzed Multicomponent Tandem Double Cyclization: A One-pot, Metal-free
Route to Synthesize Polyfunctional 4,9-Dihydropyrrolo[2,1-b]quinazolines.
AB - An acid-catalyzed multicomponent tandem double cyclization protocol has been
developed for the synthesis of polyfunctional 4,9-dihydropyrrolo[2,1
b]quinazolines from simple and readily available arylglyoxal monohydrates, 2
aminobenzylamine, and trans-beta-nitrostyrenes. This practical and metal-free
reaction proceeds through an imine formation/cyclization/Michael addition/Henry
cyclization protocol, resulting in the construction of four new bonds and two
ring moieties directly in one pot.
PMID- 27504694
TI - The role of encoding strategy in younger and older adult associative recognition:
A think-aloud analysis.
AB - Older adults have especially poor recognition memory for word pairs, and research
suggests this associative deficit manifests primarily in older adults' higher
rates of false alarms. This could result from older adults either failing to
generate meaningful (deep) mediators at study, or failing to benefit from having
generated deep mediators at test. Younger and older adults performed a
recognition memory task for words and word pairs. A think-aloud analysis of their
spontaneous encoding strategies (repetition, shallow mediators, deep mediators)
revealed that generation of deep mediators did not differ between younger and
older adults, and was associated with high hit rates for items and associates in
both age groups. However, generation of deep mediators was inversely related to
false alarm rates in younger adults but not older adults. A trial-level analysis
of encoding strategies and recognition responses revealed that younger adults
benefited from having generated deep mediators when presented with corresponding
recombined pairs at test as shown in their lower false alarm rates. In contrast,
older adults who generated deep mediators during study (e.g., to blanket-figure)
did not benefit from having done so when they encountered the corresponding
recombined pairs at test (blanket-summer and district-figure). Their false alarm
rates to pairs at test were unrelated to generation of deep mediators at study.
These results suggest that many older adults have difficulty retrieving their
mediators when presented with recombined pairs at test, or their mediators are
not distinct enough to distinguish intact pairs from recombined pairs at test, or
some combination of both. (PsycINFO Database Record
PMID- 27504695
TI - "Are vocabulary tests measurement invariant between age groups? An item response
analysis of three popular tests": Correction to Fox, Berry, and Freeman (2014).
AB - Reports an error in "Are vocabulary tests measurement invariant between age
groups? An item response analysis of three popular tests" by Mark C. Fox, Jane M.
Berry and Sara P. Freeman (Psychology and Aging, 2014[Dec], Vol 29[4], 925-938).
In the article, unneeded zeros were inadvertently included at the beginnings of
some numbers in Tables 1-4. In addition, the right column in Table 4 includes
three unnecessary zeros after asterisks. (The following abstract of the original
article appeared in record 2014-49140-001.) Relatively high vocabulary scores of
older adults are generally interpreted as evidence that older adults possess more
of a common ability than younger adults. Yet, this interpretation rests on
empirical assumptions about the uniformity of item-response functions between
groups. In this article, we test item response models of differential responding
against datasets containing younger-, middle-aged-, and older-adult responses to
three popular vocabulary tests (the Shipley, Ekstrom, and WAIS-R) to determine
whether members of different age groups who achieve the same scores have the same
probability of responding in the same categories (e.g., correct vs. incorrect)
under the same conditions. Contrary to the null hypothesis of measurement
invariance, datasets for all three tests exhibit substantial differential
responding. Members of different age groups who achieve the same overall scores
exhibit differing response probabilities in relation to the same items
(differential item functioning) and appear to approach the tests in qualitatively
different ways that generalize across items. Specifically, younger adults are
more likely than older adults to leave items unanswered for partial credit on the
Ekstrom, and to produce 2-point definitions on the WAIS-R. Yet, older adults
score higher than younger adults, consistent with most reports of vocabulary
outcomes in the cognitive aging literature. In light of these findings, the most
generalizable conclusion to be drawn from the cognitive aging literature on
vocabulary tests is simply that older adults tend to score higher than younger
adults, and not that older adults possess more of a common ability.
PMID- 27504696
TI - 25G PARS PLANA VITRECTOMY AND IRIDO-ZONULO-HYALOIDO-VITRECTOMY IN THE MANAGEMENT
OF MALIGNANT GLAUCOMA IN PHAKIC EYES FOLLOWING TRABECULECTOMY.
AB - PURPOSE: To describe a new surgical technique in the management of malignant
glaucoma in phakic eyes. METHODS: We performed 25-gauge pars plana vitrectomy
with anterior irido-zonulo-hyaloido-vitrectomy in 2 young phakic patients with
malignant glaucoma after trabeculectomy. This technique allowed posteroanterior
aqueous communication, relieved aqueous misdirection, helped restoring anterior
chamber depth, normalized the intraocular pressure and most importantly helped to
preserve the crystalline lens. RESULTS: At 8 months follow-up, both patients have
stable visual acuity, normal intraocular pressure, well-functioning blebs, and
clear crystalline lens. CONCLUSION: One can consider 25-gauge pars plana
vitrectomy with anterior irido-zonulo-hyaloido-vitrectomy as a safe and effective
treatment option for the management of malignant glaucoma in phakic eyes.
PMID- 27504697
TI - FULL-THICKNESS MACULAR HOLE COMBINED WITH PIGMENT EPITHELIAL DETACHMENT USING
MULTIMODAL IMAGING.
AB - PURPOSE: To describe two patients who showed full-thickness macular holes (FTMH)
combined with pigment epithelial detachments (PED) and had contrasting outcomes
to treatment. METHODS: A retrospective report of two cases. RESULTS: Case 1 was
treated with intravitreal antivascular endothelial growth factor and photodynamic
therapy, and the PED flattened. Subsequently, a vitrectomy was performed and the
FTMH closed. Her visual acuity improved from 20/200 to 20/25. In Case 2, the same
medical therapy, with less frequency compared with Case 1, did not affect the
PED, and the FTMH failed to close with surgery. Later, a spontaneous collapse of
the PED occurred but the FTMH was persistent with an associated poor visual
acuity of 20/200. CONCLUSION: Full-thickness macular hole is rare, but can occur
in association with large PEDs. Although the pathologic mechanism was uncertain,
visual outcomes were dependent on response to treatments of the PED, as well as
anatomical closure of the FTMH.
PMID- 27504698
TI - Charge Density and Electrostatic Potential Study of 16alpha,17beta-Estriol and
the Binding of Estrogen Molecules to the Estrogen Receptors ERalpha and ERbeta.
AB - An accurate X-ray diffraction study at 20 K combined with DFT theoretical
calculations has been performed for the estriol crystal with two conformationally
different molecules in the asymmetric unit. The electron density has been modeled
via a multipole expansion, using both experimental and theoretical structure
factors, and a topological analysis has been performed. The experimental
molecular geometry, hydrogen bonding, atomic charges, dipole moments, and other
topological characteristics are compared with those calculated theoretically. In
particular, the molecular electrostatic potential has been extracted and compared
with those reported for other estrogen molecules exhibiting different binding
affinities to the estrogen receptors (ERalpha and ERbeta).
PMID- 27504699
TI - Fall Prevention in a Primary Care Setting.
AB - BACKGROUND: Falls and fall-related injuries are common in community-dwelling
elderly people. Effective multifactorial fall prevention programs in the primary
care setting may be a promising approach to reduce the incidence rate of falls.
METHODS: In a cluster randomized trial in 33 general practices 378 people living
independently and at high risk of falling (65 to 94 years old; 285 women) were
allocated to either a 16 week exercise-based fall prevention program including
muscle strengthening and challenging balance training exercises, combined with a
12 week home-based exercise program (222 participants), or to usual care (156
participants). The main outcome was number of falls over a period of 12 months.
Secondary outcomes were the number of fall-related injuries, physical function
(Timed-Up-and-Go-Test, TUG, Chair-Stand-Test, CST, modified Romberg Test), and
fear of falling. RESULTS: In the intervention group (n=222 patients in 17 general
practices) 291 falls occurred, compared to 367 falls in the usual care group
(n=156 patients in 16 general practices). We observed a lower incidence rate for
falls in the intervention group (incidence rate ratio/IRR: 0.54; 95% confidence
interval (CI): [0.35; 0.84], p=0.007) and for fall-related injuries (IRR: 0.66;
[0.42; 0.94], p=0.033). Additionally, patients in the intervention group showed
significant improvements in secondary endpoints (TUG: -2.39 s, [-3.91; -0.87],
p=0.014; mRomberg: 1.70 s, [0.35; 3.04], p=0.037; fear of falling: -2.28 points,
[-3.87; -0.69], p=0.022) compared to usual care. CONCLUSION: A complex falls
prevention program in a primary care setting was effective in reducing falls and
fall-related injuries in community dwelling older adults at risk.
PMID- 27504700
TI - Prospective Studies from Germany Are Lacking.
PMID- 27504701
TI - In Reply.
PMID- 27504702
TI - Relevant Errors Relating to the Measuring Method.
PMID- 27504703
TI - In Reply.
PMID- 27504704
TI - Intra-arterial Treatment.
PMID- 27504705
TI - Hemodilution.
PMID- 27504706
TI - In Reply.
PMID- 27504707
TI - The Diagnosis and Treatment of Hair and Scalp Diseases.
AB - BACKGROUND: Hair loss is caused by a variety of hair growth disorders, each with
its own pathogenetic mechanism. METHODS: This review is based on pertinent
articles retrieved by a selective search in PubMed, on the current German and
European guidelines, and on the authors' clinical and scientific experience.
RESULTS: Excessive daily hair loss (effluvium) may be physiological, as in the
postpartum state, or pathological, due for example to thyroid disturbances, drug
effects, iron deficiency, or syphilis. Androgenetic alopecia generally manifests
itself in women as diffuse thinning of the hair over the top of the scalp, and in
men as receding temporal hairlines and loss of hair in the region of the whorl on
the back of the head. Alopecia areata is patchy hair loss arising over a short
time and involving the scalp, eyebrows, beard, or entire body. The hair loss of
alopecia areata is reversible in principle but hard to treat. Folliculitis
decalvans is a form of alopecia with scarring, characterized by inflamed papules,
pustules, and crusts at the edges of the lesions. Lichen planopilaris generally
presents with small patches of baldness, peripilar erythema, and round areas of
skin scaling. Kossard's frontal fibrosing alopecia is characterized by a receding
hairline and loss of eyebrows. CONCLUSION: Hair loss is a symptom, not a
diagnosis. The pathogenesis of the alopecias involves a range of genetic,
endocrine, immune, and inflammatory processes, each of which calls for its own
form of treatment.
PMID- 27504708
TI - Decoration of silicon nanowires with silver nanoparticles for ultrasensitive
surface enhanced Raman scattering.
AB - Silicon nanowires (Si NWs), produced by the chemical etching technique, were
decorated with silver nanoparticles (NPs) produced at room temperature by the
pulsed laser deposition (PLD) technique. Silver NPs were obtained by means of
nanosecond pulsed laser ablation of a target in the presence of a controlled Ar
atmosphere. Two different laser pulse numbers and Si NWs having different lengths
were used to change the NP number density on the Si NW surface. The resulting Ag
NP morphologies were studied by scanning electron microscopy imaging. The results
show that this industrially compatible technological approach allows the coverage
of the Si NW walls with Ag NPs with a strong control of the NP size distribution
and spatial arrangement. The obtained Ag NP decorated Si NWs are free from
chemicals contamination and there is no need of post deposition high temperature
processes. The optical properties of Si NW arrays were investigated by
reflectance spectroscopy that showed the presence of a plasmon related absorption
peak, whose position and width is dependent on the Ag NP surface morphology.
Coupling the huge surface-to-volume ratio of Si NW arrays with the plasmonic
properties of silver nanoparticles resulted in a 3D structure suitable for very
sensitive surface enhanced Raman scattering (SERS) applications, as demonstrated
by the detection of Rhodamine 6G in aqueous solution at a concentration level of
10(-8) M.
PMID- 27504709
TI - Association of Xerostomia and Ultrasonographic Features of the Major Salivary
Glands After Radioactive Iodine Ablation for Papillary Thyroid Carcinoma.
AB - OBJECTIVE: The objective of this study is to evaluate the association between
xerostomia and sonographic features of the major salivary glands after patients
undergo radioactive iodine ablation (RIA) for papillary thyroid carcinoma (PTC).
MATERIALS AND METHODS: The study included 256 consecutive patients who underwent
total thyroidectomy, RIA, and neck ultrasound examinations. Changes in the
ultrasound features of the parotid and submandibular glands after RIA were
evaluated retrospectively by a single radiologist, on the basis of direct
comparison of sonograms obtained before and after RIA. Clinical data, including
the presence of xerostomia, were investigated retrospectively by the same
radiologist via a review of the electronic medical records. RESULTS: For 111 of
the 256 patients (43.4%), ultrasound examination revealed changes in the major
salivary glands after RIA. The presence of xerostomia was undetermined in 85 of
the 256 patients. Among the remaining 171 patients, the frequency of xerostomia
was 36.8% (63/171). When patients with xerostomia were compared with those
without xerostomia, no statistically significant differences in patient sex and
age, the dose of RIA received, or the number of RIA sessions were noted (p >
0.05). Considering the changes in the ultrasound features of the major salivary
glands after RIA, no statistically significant association was found between
xerostomia and the number of involved major salivary glands or the presence of an
involved submandibular gland (p > 0.05). CONCLUSION: In this study, ultrasound
was unhelpful for evaluating xerostomia after RIA in patients with PTC.
PMID- 27504710
TI - Using two tools to identify Potentially Inappropriate Medications (PIM) in
elderly patients in Southern Chile.
AB - OBJECTIVES: To assess and compare the prevalence of prescribing of potentially
inappropriate medications (PIMs) identified using the Beers and STOPP criteria;
and to determine the clinical variables related with the prescription of PIMs in
older adults. METHODS: An observational study of 250 patients aged 65 years or
older was conducted in a large teaching hospital. Beers (2012) and STOPP (2008)
criteria were utilized to identify PIMs. Data on age, sex, admission and
discharge dates, diagnoses, and medications prescribed were obtained from medical
records. Multivariate logistic regression was used to determine patient variables
related with the prescription of PIMs. KEY FINDINGS: Using Beers criteria, 375
PIMs were identified in 198 patients. 32% of these patients were prescribed one
PIM, 20% were prescribed two PIMs, and 48% were prescribed more than two PIMs.
Using STOPP criteria, 148 PIMs were identified in 120 patients. 41% of these
patients were prescribed one PIM, 51% were prescribed two PIMs, and 8% were
prescribed more than two PIMs. An association between PIM prescribing and
polypharmacy was detected with both criteria. After adjusting for confounding
variables, the prescription of Beers-identified PIMs was significantly associated
with patients older than 80 (OR: 2.99; 95% CI: 1.13-7.89) and with length of
hospital stay of more than 15days (OR: 2.78; 95% CI: 1.20-6.44). CONCLUSION:
These two criteria showed that the prescription of PIMs is prevalent in
hospitalized elderly patients. It may be beneficial to educate healthcare teams
about these criteria to reduce the prescription of PIMs.
PMID- 27504711
TI - Use of NMR-Based Metabolomics To Chemically Characterize the Roasting Process of
Chicory Root.
AB - Roasted chicory root (Cichorium intybus) has been widely accepted as the most
important coffee substitute. In this study, a nuclear magnetic resonance (NMR)
based comprehensive analysis was performed to monitor the substantial changes in
the composition of chicory root during the roasting process. A detailed signal
assignment of dried raw and roasted chicory roots was carried out using 1H, 13C,
1H-1H DQF-COSY, 1H-13C edited-HSQC, 1H-13C CT-HMBC, and 1H-13C HSQC-TOCSY NMR
spectra. On the basis of the signal assignments, 36 NMR-visible components were
monitored simultaneously during roasting. Inulins, sucrose, and most of the amino
acids were largely degraded during the roasting process, whereas monosaccharides
decreased at the beginning and then increased until the dark roasting stage.
Acetamide, 5-hydroxymethylfurfural, di-d-fructose dianhydride, and norfuraneol
were newly formed during roasting. Furthermore, a principal component analysis
score plot indicated that similar chemical composition profiles could be achieved
by roasting the chicory root either at a higher firepower for a shorter time or
at a lower firepower for a longer time.
PMID- 27504712
TI - MAP4K4 deficiency in CD4(+) T cells aggravates lung damage induced by ozone
oxidized black carbon particles.
AB - As the main composition of combustion, black carbon (BC) is becoming more and
more noticeable at home and abroad. Ozone-oxidized black carbon (oBC) was
produced through aging of ozone, one of the near-surface pollutants, to black
carbon. And oBC was found to be more oxidation and cell toxicity when compared
with BC. Besides, as a key cell of immunity, whether CD4(+) T cell would involve
in lung inflammation induced by particular matter is still unclear. This study
aims to observe the effect of oBC on lung damage in mice and discuss how the
functional MAP4K4 defect CD4(+) T cells (conditional knockout of MAP4K4) presents
its role in this process. In our study, MAP4K4 deletion in CD4(+) T cells (MAP4K4
cKO) could increase cell number of macrophages, lymphocytes and neutrophils in
bronchoalveolar lavage fluid (BALF) exposed to oBC. MAP4K4 deletion in CD4(+) T
cell also affected CD4(+) T cell differentiation in mediastinal lymph nodes after
oBC stimulation. The number of CD4(+) IL17(+) T cell increased obviously. The
levels of IL-6 mRNA of lung in MAP4K4 cKO mice was higher than that in wild type
mice after exposed to oBC, while the level of IL-6 in BALF had the same trend.
Histological examination showed that MAP4K4 deletion in CD4(+) T cells affected
lung inflammation induced by oBC. Results indicated that MAP4K4 cKO in CD4(+) T
cells upgraded the level of inflammation in lung when exposed to oBC, which may
be connected to the CD4(+) T cell differentiation and JNK, ERK and P38 pathways.
PMID- 27504713
TI - Comparison of ferumoxytol-enhanced MRA with conventional angiography for
assessment of severity of transplant renal artery stenosis.
AB - PURPOSE: To determine the accuracy of ferumoxytol-enhanced magnetic resonance
angiography (MRA) in assessing the severity of transplant renal artery stenosis
(TRAS), using digital subtraction angiography (DSA) as the reference standard.
MATERIALS AND METHODS: Our Institutional Review Board approved this
retrospective, Health Insurance Portability and Accountability Act-compliant
study. Thirty-three patients with documented clinical suspicion for TRAS
(elevated serum creatinine, refractory hypertension, edema, and/or audible bruit)
and/or concerning sonographic findings (elevated renal artery velocity and/or
intraparenchymal parvus tardus waveforms) underwent a 1.5T MRA with ferumoxytol
prior to DSA. All DSAs were independently reviewed by an interventional
radiologist and served as the reference standard. The MRAs were reviewed by three
readers who were blinded to the ultrasound and DSA findings for the presence and
severity of TRAS. Sensitivity, specificity, and accuracy for identifying
substantial stenoses (>50%) were determined. Intraclass correlation coefficients
(ICCs) were calculated among readers. Mean differences between the percent
stenosis from each MRA reader and DSA were calculated. RESULTS: On DSA, a total
of 42 stenoses were identified in the 33 patients. The sensitivity, specificity,
and accuracy of MRA in detecting substantial stenoses were 100%, 75-87.5%, and
95.2-97.6%, respectively, among the readers. There was excellent agreement among
readers as to the percent stenosis (ICC = 0.82). MRA overestimated the degree of
stenosis by 3.9-9.6% compared to DSA. CONCLUSION: Ferumoxytol-enhanced MRA
provides high sensitivity, specificity, and accuracy for determining the severity
of TRAS. Our results suggest that it can potentially be used as a noninvasive
examination following ultrasound to reduce the number of unnecessary conventional
angiograms. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:779-785.
PMID- 27504714
TI - Could MRI Become the First-Line Investigation in Suspected Appendicitis?
PMID- 27504715
TI - Shuttling of (deoxy-) purine nucleotides between compartments of the diatom
Phaeodactylum tricornutum.
AB - Diatom plastids show several peculiarities when compared with primary plastids of
higher plants or algae. They are surrounded by four membranes and depend on
nucleotide uptake because, unlike in plants, nucleotide de novo synthesis
exclusively occurs in the cytosol. Previous analyses suggest that two
specifically adapted nucleotide transporters (NTTs) facilitate the required
passage of nucleotides across the innermost plastid membrane. However, nucleotide
transport across the additional plastid membranes remains to be clarified.
Phylogenetic studies, transport assays with the recombinant protein as well as
GFP-based targeting analyses allowed detailed characterization of a novel isoform
(PtNTT5) of the six NTTs of Phaeodactylum tricornutum. PtNTT5 exhibits low amino
acid similarities and is only distantly related to all previously characterized
NTTs. However, in a heterologous expression system, it acts as a nucleotide
antiporter and prefers various (deoxy-) purine nucleotides as substrates.
Interestingly, PtNTT5 is probably located in the endoplasmic reticulum, which in
diatoms also represents the outermost plastid membrane. PtNTT5, with its unusual
transport properties, phylogeny and localization, can be taken as further
evidence for the establishment of a sophisticated and specifically adapted
nucleotide transport system in diatom plastids.
PMID- 27504716
TI - Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and
Irritants on Adult-Onset Asthma in Three European Studies.
AB - BACKGROUND: The biological mechanisms by which cleaning products and
disinfectants-an emerging risk factor-affect respiratory health remain
incompletely evaluated. Studying genes by environment interactions (G * E) may
help identify new genes related to adult-onset asthma. OBJECTIVES: We identified
interactions between genetic polymorphisms of a large set of genes involved in
the response to oxidative stress and occupational exposures to low molecular
weight (LMW) agents or irritants on adult-onset asthma. METHODS: Our data came
from three large European cohorts: Epidemiological Family-based Study of the
Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution
and Lung and Heart Disease in Adults (SAPALDIA), and European Community
Respiratory Health Survey in Adults (ECRHS). A candidate pathway-based strategy
identified 163 genes involved in the response to oxidative stress and potentially
related to exposures to LMW agents/irritants. Occupational exposures were
evaluated using an asthma job-exposure matrix and job-specific questionnaires for
cleaners and healthcare workers. Logistic regression models were used to detect G
* E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults
(mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were
corrected for multiple comparisons. RESULTS: Ever exposure to LMW
agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95%
CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure
interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome
1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980,
chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and
PRKCA (rs6504453, chromosome 17). Results were consistent across the three
studies and after accounting for smoking. CONCLUSIONS: Using a pathway-based
selection process, we identified novel genes potentially involved in adult asthma
by interaction with occupational exposure. These genes play a role in the NF
kappaB pathway, which is involved in inflammation. Citation: Rava M, Ahmed I,
Kogevinas M, Le Moual N, Bouzigon E, Curjuric I, Dizier MH, Dumas O, Gonzalez JR,
Imboden M, Mehta AJ, Tubert-Bitter P, Zock JP, Jarvis D, Probst-Hensch NM,
Demenais F, Nadif R. 2017. Genes interacting with occupational exposures to low
molecular weight agents and irritants on adult-onset asthma in three European
studies. Environ Health Perspect 125:207-214; http://dx.doi.org/10.1289/EHP376.
PMID- 27504717
TI - Positional plagiocephaly reduces parental adherence to SIDS Guidelines and
inundates the health system.
AB - BACKGROUND: This study sought to better understand parent, grandparent and
clinician views of prevention, treatment and costs of plagiocephaly. METHODS: A
qualitative study was conducted using focus groups and semi-structured
interviews. A grounded theory approach was taken to build theories from the
qualitative data collected. A subjectivist epistemological orientation was taken
under the paradigm of positivism. RESULTS: Ninety-one parents, 6 grandparents and
24 clinicians were recruited from the community as well as primary and tertiary
care clinics. Plagiocephaly worried most parents because it could permanently
affect their child's 'looks' and some thought it would affect a child's
development. Parents were 'willing to do anything' to prevent plagiocephaly
including using products or sleeping positions that are contraindicated under
sudden infant death syndrome guidelines. Parents found the care pathway
convoluted and inconsistent messages were given from different health providers.
For clinicians, the high prevalence of flat head is 'clogging up their patient
pool', taking up time they used to spend with children with more severe
conditions. CONCLUSION: There is a need to re-emphasize sudden infant death
syndrome guidelines for families when they present with an infant with
plagiocephaly. Stronger messaging regarding the lack of safety of current pillows
marketed to prevent flat head may be useful to decrease their use. Increasing
education for all health professionals including general practitioners, allied
health and complementary health providers and standardizing assessment and
referral criteria may allow the majority of diagnosis and treatment of positional
plagiocephaly to occur at points of first contact (e.g. general practitioners,
community nurse) and may prevent further burden on the health care system.
PMID- 27504718
TI - Chemoselective Preparation of Clickable Aryl Sulfonyl Fluoride Monomers: A
Toolbox of Highly Functionalized Intermediates for Chemical Biology Probe
Synthesis.
AB - Sulfonyl fluoride (SF)-based activity probes have become important tools in
chemical biology. Herein, exploiting the relative chemical stability of SF to
carry out a number of unprecedented SF-sparing functional group manipulations, we
report the chemoselective synthesis of a toolbox of highly functionalized aryl SF
monomers that we used to quickly prepare SF chemical biology probes. In addition
to SF, the monomers bear an embedded click handle (a terminal alkyne that can
perform copper(I)-mediated azide-alkyne cycloaddition). The monomers can be used
either as fragments to prepare clickable SF analogues of drugs (biologically
active compounds) bearing an aryl ring or, alternatively, attached to drugs as
minimalist clickable aryl SF substituents.
PMID- 27504719
TI - Encapsulation of Perovskite Solar Cells for High Humidity Conditions.
AB - We examined different encapsulation strategies for perovskite solar cells by
testing the device stability under continuous illumination, elevated temperature
(85 degrees C) and ambient humidity of 65 %. The effects of the use of different
epoxies, protective layers and the presence of desiccant were investigated. The
best stability (retention of ~80 % of initial efficiency on average after 48 h)
was obtained for devices protected by a SiO2 film and encapsulated with a UV
curable epoxy including a desiccant sheet. However, the stability of ZnO-based
cells encapsulated by the same method was found to be inferior to that of TiO2
based cells. Finally, outdoor performance tests were performed for TiO2 -based
cells (30-90 % ambient humidity). All the stability tests were performed
following the established international summit on organic photovoltaic stability
(ISOS) protocols for organic solar cell testing (ISOS-L2 and ISOS-O1).
PMID- 27504720
TI - Characterization of Medication Velocity and Size Distribution from Pressurized
Metered-Dose Inhalers by Phase Doppler Anemometry.
AB - BACKGROUND: Particle size and velocity are two of the most significant factors
that impact the deposition of pressurized metered-dose inhaler (pMDI) sprays in
the mouth cavity. pMDIs are prominently used around the world in the treatment of
patients suffering from a variety of lung diseases such as asthma and chronic
obstructive pulmonary disease. Since their introduction in the field, and as a
result of their effectiveness and simplicity of usage, pMDIs are considered to be
the most widely prescribed medical aerosol delivery system. METHODS: In the
current study, particle velocity and size distribution were measured at three
different locations along the centerline of a pMDI spray using Phase Doppler
Anemometry. pMDIs from four different pharmaceutical companies were tested, each
using salbutamol sulfate as the medication. RESULTS AND CONCLUSIONS: Measurements
along at the pMDI centerline (at 0, 75, and 100 mm downstream of the inhaler
mouthpiece) showed that the spray velocities were bimodal in time for all four
pMDI brands. The first peak occurred as the spray was leaving the mouthpiece,
while the second peak (at the same location, 0 mm) occurred at around 60, 95, 95,
and 115 milliseconds later, respectively, for the four tested inhalers, with a
drop in the velocity between the two peaks. Three probability density functions
(PDFs) were tested, and the Rosin-Rammler PDF best fit the empirical data, as
determined using a chi-squared test. These results suggest that there is a
difference in the mean particle velocities at the centerline for the tested pMDIs
and the diameter of released particles varied statistically for each brand.
PMID- 27504721
TI - Dithiocarbamate Self-Assembled Monolayers as Efficient Surface Modifiers for Low
Work Function Noble Metals.
AB - Tuning the work function of the electrode is one of the crucial steps to improve
charge extraction in organic electronic devices. Here, we show that N,N-dialkyl
dithiocarbamates (DTC) can be effectively employed to produce low work function
noble metal electrodes. Work functions between 3.1 and 3.5 eV are observed for
all metals investigated (Cu, Ag, and Au). Ultraviolet photoemission spectroscopy
(UPS) reveals a maximum decrease in work function by 2.1 eV as compared to the
bare metal surface. Electronic structure calculations elucidate how the complex
interplay between intrinsic dipoles and dipoles induced by bond formation
generates such large work function shifts. Subsequently, we quantify the
improvement in contact resistance of organic thin film transistor devices with
DTC coated source and drain electrodes. These findings demonstrate that DTC
molecules can be employed as universal surface modifiers to produce stable
electrodes for electron injection in high performance hybrid organic
optoelectronics.
PMID- 27504722
TI - Biocatalytic Dynamic Kinetic Resolution for the Synthesis of Atropisomeric Biaryl
N-Oxide Lewis Base Catalysts.
AB - Atropisomeric biaryl pyridine and isoquinoline N-oxides were synthesized
enantioselectively by dynamic kinetic resolution (DKR) of rapidly racemizing
precursors exhibiting free bond rotation. The DKR was achieved by ketoreductase
(KRED) catalyzed reduction of an aldehyde to form a configurationally stable
atropisomeric alcohol, with the substantial increase in rotational barrier
arising from the loss of a bonding interaction between the N-oxide and the
aldehyde. Use of different KREDs allowed either the M or P enantiomer to be
synthesized in excellent enantiopurity. The enantioenriched biaryl N-oxide
compounds catalyze the asymmetric allylation of benzaldehyde derivatives with
allyltrichlorosilane.
PMID- 27504723
TI - [Editor's Comment].
PMID- 27504724
TI - [Needle electromyography of facial muscles].
PMID- 27504725
TI - [Not Available].
PMID- 27504726
TI - [Lipoid Pneumonia Associated with Lipid-Containing Nasal Sprays and Nose Drops].
AB - BACKGROUND: Regularly updating the German pharmacopoeia on contemporary
preparations DAC/NRF, chapter "Nasal Applications" and the recommendations on
"Nasal Oils" as well as "Nasal Ointments and Emulsions", the issue of the risk of
lipoid pneumonia associated with the use of plant oils and when compared to
mineral oils arose. MATERIAL AND METHODS: We searched different databases: the
"Grosse Deutsche Arzneimittelspezialitaten-Taxe" containing all products
available in German pharmacies, the Cochrane Library, the pharmacovigilance
database of the BfArM, and Medline to evaluate the benefit/risk-ratio of plant
oils in nasal drops and sprays. RESULTS: In German pharmacies, a number of both,
mineral oil-containing drugs for nasal application and plant oil-containing
medical devices are available. The risk of lipoid pneumonia described for mineral
oil-containing nasal products can not entirely be transferred to plant oil
containing products. However, evidence from the literature suggests a risk for
lipoid pneumonia, which needs to be considered given the non-proven efficacy of
such medical devices in the majority of proposed indications. To minimize risks,
recommendations are made for patient groups that should not use lipid-containing
nasal products. CONCLUSIONS: Acknowledging the potential lethal outcome of lipoid
pneumonia, a demanding diagnosis, and absence of a specific therapy, lipid
containing nasal products should be used only with great caution. Based on the
current knowledge, the statements regarding the risk of lipoid pneumonia for
lipid-containing nasal products in the DAC/NRF should not be modified.
PMID- 27504727
TI - [Eustachian Tube Dilatation? What are the Pros?].
PMID- 27504728
TI - [Eustachian Tube Dilatation? What are the Cons?].
PMID- 27504729
TI - [Not Available].
PMID- 27504730
TI - [Headache and Degraded Speech Recognition in a Patient with Unilateral Cochlear
Implant].
PMID- 27504731
TI - [Cave on Early Discharge Against Medical Advises: More Liability Less Money].
PMID- 27504732
TI - [Not Available].
PMID- 27504734
TI - [Not Available].
PMID- 27504733
TI - [Not Available].
PMID- 27504736
TI - Microencapsulation of advanced solvents for carbon capture.
AB - Purpose-designed, water-lean solvents have been developed to improve the energy
efficiency of CO2 capture from power plants, including CO2-binding organic
liquids (CO2BOLs) and ionic liquids (ILs). Many of these solvents are highly
viscous or change phases, posing challenges for conventional process equipment.
Such problems can be overcome by encapsulation. Micro-Encapsulated CO2 Sorbents
(MECS) consist of a CO2-absorbing solvent or slurry encased in spherical, CO2
permeable polymer shells. The resulting capsules have diameters in the range of
100-600 MUm, greatly increasing the surface area and CO2 absorption rate of the
encapsulated solvent. Encapsulating these new solvents requires careful selection
of shell materials and fabrication techniques. We find several common classes of
polymers are not compatible with MECS production, but we develop two custom
formulations, a silicone and an acrylate, that show promise for encapsulating
water-lean solvents. We make the first demonstration of an encapsulated IL for
CO2 capture. The rate of CO2 absorption is enhanced by a factor of 3.5 compared
to a liquid film, a value that can be improved by further development of shell
materials and fabrication techniques.
PMID- 27504737
TI - The induction of CXCR4 expression in human osteoblast-like cells (MG63) by CoCr
particles is regulated by the PLC-DAG-PKC pathway.
AB - BACKGROUND: Osteolysis which leads to aseptic loosening of implants is a
fundamental problem in joint replacement surgery (arthroplasty) and the leading
cause for implant failure and revision surgery. Metal (CoCr) particles separated
from implants by wear cause osteolysis and the failure of orthopedic implants,
but the molecular mechanism is not clear. The chemokine receptor CXCR4 has been
shown to play a pivotal role in periprosthetic osteolysis. The aim of this study
was to determine which signal transduction pathway (PLC-DAG-PKC or MAPK/ERK)
induces CXCR4 expression in osteoblast-like cells (MG63) cells. METHODS: MG63 and
Jurkat cells were stimulated with different amounts of particles (107 , 106 , and
105 ) for different time periods (30 min to 24 h), in the presence and absence of
specific inhibitors (chelerythrine for the PLC-DAG-PKC pathway and PD98059 for
the MAPK/ERK pathway). The expression of CXCR4-specific mRNA was determined by
real-time polymerase chain reaction (PCR), and the PKC activity was measured by
Western Blot using an antibody specific for PKC-related phosphorylation. RESULTS:
Real-time PCR data showed that CXCR4 mRNA expression in MG63 cells induced by
CoCr particles was significantly diminished by the PKC-specific inhibitor
chelerythrine. This effect was not observed with the MAPK/ERK inhibitor PD98059.
The involvement of PKC was also confirmed by an intensified phosphorylation
pattern after stimulation with CoCr particles. In Jurkat cells, none of the
inhibitors exhibited any effect. CONCLUSION: The induction of CXCR4-specific mRNA
expression in MG63 cells after stimulation with CoCr particles is regulated by
the PLC-DAG-PKC pathway and not by the MAPK/ERK pathway. (c) 2016 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2326-2332,
2017.
PMID- 27504738
TI - Near-Infrared Polymeric Nanoparticles with High Content of Cyanine for Bimodal
Imaging and Photothermal Therapy.
AB - The discovery and synthesis of theranostic nanomedicines with high loading of
imaging and therapeutic agents is challenging. In this work, a polymer assembling
strategy was used to make nanoparticles with exceptionally high loading of
theranostic agent. As an example, poly(heptamethine) was synthesized via
multicomponent Passerini reaction, and then assembled into nanoparticles in the
presence of poly(ethylene glycol)2k-block-poly(d,l-lactide)2k (PEG-PLA) with high
heptamethine loading (>50%). The formed nanoparticles could be used for bimodal
bioimaging and photothermal therapy. The bimodal bioimaging provided
complementary message about biodistribution, and photothermal treatment inhibited
the growth of cervical carcinoma upon laser irradiation. This assembly of
polymers formed by imaging and therapeutic agents opens new possibilities for the
construction of multifunctional nanomedicines.
PMID- 27504739
TI - Methylglyoxal is associated with changes in kidney function among individuals
with screen-detected Type 2 diabetes mellitus.
AB - AIMS: The glycolysis-derived metabolite methylglyoxal has been linked to clinical
microvascular complications, including diabetic nephropathy. We aimed to further
investigate the hypothesis that methylglyoxal is involved in decline in renal
function by assessing the associations between measures of renal function during
a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part
of the Danish arm of the ADDITION-Europe trial (ADDITION-DK). METHODS: Biobank
serum samples collected at ADDITION-DK baseline (2001-2006) and follow-up (2009
2010) were used in the current analysis of methylglyoxal. We assessed cross
sectional baseline and longitudinal associations between methylglyoxal and
urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between
methylglyoxal and categories of albuminuria or reduced eGFR. RESULTS: Baseline
methylglyoxal was positively associated with ACR at baseline (12% higher ACR per
doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of
follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m2 per
doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c ,
systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid
lowering treatment, C-reactive protein and smoking. CONCLUSIONS: In a population
of people with screen-detected Type 2 diabetes, we observed associations between
methylglyoxal and markers of renal function: 6-year change in methylglyoxal was
inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline
was positively associated with ACR at baseline. Our study lends further support
to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.
PMID- 27504740
TI - Influence of the anti-inflammatory cytokine interleukin-4 on human joint capsule
myofibroblasts.
AB - Post-traumatic joint contracture was reported to be associated with elevated
numbers of contractile myofibroblasts (MFs) in the healing capsule. During the
physiological healing process, the number of MFs declines; however, in
fibroconnective disorders, MFs persist. The manifold interaction of the cytokines
regulating the appearance and persistence of MFs in the pathogenesis of joint
contracture remains to be elucidated. The objective of our current study was to
analyze the impact of the anti-inflammatory cytokine interleukin (IL)-4 on
functional behavior of MFs. Cells were isolated from human joint capsule
specimens and challenged with three different concentrations of IL-4 with or
without its neutralizing antibody. MF viability, contractile properties, and the
gene expression of both alpha-smooth muscle actin (alpha-SMA) and collagen type I
were examined. Immunofluorescence staining revealed the presence of IL-4 receptor
(R)-alpha (alpha) on the membrane of cultured MFs. The cytokine IL-4 promoted MF
viability and enhanced MF modulated contraction of collagen gels. Moreover, IL-4
intervened in gene expression by up-regulation of alpha-SMA and collagen type I
mRNA. These effects could be specifically lowered by the neutralizing IL-4
antibody. On the basis of our findings we conclude that the anti-inflammatory
cytokine IL-4 specifically regulates viability and the contractile properties of
MFs via up-regulating the gene expression of alpha-SMA and collagen type I. IL-4
may be a helpful target in developing anti-fibrotic therapeutics for post
traumatic joint contracture in human. (c) 2016 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 35:1290-1298, 2017.
PMID- 27504741
TI - Importance of spike timing in touch: an analogy with hearing?
AB - Touch is often conceived as a spatial sense akin to vision. However, touch also
involves the transduction and processing of signals that vary rapidly over time,
inviting comparisons with hearing. In both sensory systems, first order afferents
produce spiking responses that are temporally precise and the timing of their
responses carries stimulus information. The precision and informativeness of
spike timing in the two systems invites the possibility that both implement
similar mechanisms to extract behaviorally relevant information from these
precisely timed responses. Here, we explore the putative roles of spike timing in
touch and hearing and discuss common mechanisms that may be involved in
processing temporal spiking patterns.
PMID- 27504742
TI - Topical cetirizine and oral vitamin D: a valid treatment for hypotrichosis caused
by ectodermal dysplasia.
AB - BACKGROUND: Ectodermal dysplasia is a clinically and genetically heterogeneous
group of inherited disorders characterized by abnormal development of two or more
of the following ectodermal-derived structures: hair, teeth, nails and sweat
glands. The hair is the most frequently affected structure. Hair shaft
abnormalities are of great concern to these patients, but no effective treatments
are available. METHODS: We describe three girls with congenital hypotrichosis (9,
5 and 6 years old) caused by ectodermal dysplasia treated with topical cetirizine
solution (2 mL. once daily) and oral vitamin D supplementation (1000 IU daily).
RESULTS: After 6 months of treatment, the density of hair on the scalp increased
in all patients. The vellus hair was replaced by terminal hair. Hair regrowth was
evaluated both from the clinical and trichoscopic point of view. CONCLUSION: We
propose a combination of topical cetirizine and oral vitamin D as a rational
treatment of choice in congenital hypotrichosis caused by ectodermal dysplasia.
PMID- 27504743
TI - Unusual Mn(III/IV)4 Cubane and Mn(III)16M4 (M = Ca, Sr) Looplike Clusters from
the Use of Dimethylarsinic Acid.
AB - Three complexes are reported from the initial use of dimethylarsinic acid
(Me2AsO2H) in Mn(III/IV) cluster chemistry, [Mn4O4(O2AsMe2)6] (3; 2Mn(III),
2Mn(IV)), and [Mn16X4O8(O2CPh)16(Me2AsO2)24] (X = Ca(2+) (4) or Sr(2+) (5);
16Mn(III)). They were obtained from reactions with [Mn12O12(O2CR)16(H2O)4] (R =
Me, Ph) either without (3) or with (4 and 5) the addition of X(2+) salts. Complex
3 contains a [Mn4O4](6+) cubane, whereas isostructural 4 and 5 contain a planar
loop structure comprising four Mn4 asymmetric "butterfly" units linked by
alternating anti,anti MU-O2AsMe2 and {X2(O2AsMe2)(O2CPh)2} units. Variable
temperature magnetic susceptibility (chiM) data were collected on dried
microcrystalline samples of 3-5 in the 5.0-300 K range in a 0.1 T (1000 G) direct
current (dc) magnetic field. Data for 3 were fit to the appropriate Van Vleck
equation (using the [Formula: see text] = -2JSi.Sj convention) for a cubane of
virtual C2v symmetry, giving J33 = 0.0(1) cm(-1), J34 = -3.4(4) cm(-1), J44 =
9.8(2) cm(-1), and g = 1.99(1), where the Jij subscripts refer to the oxidation
states of the interacting Mn atoms. The ground state thus consists of two coupled
Mn(IV) and two essentially noninteracting Mn(III). For 4 and 5, low-lying excited
states from the high nuclearity and weak couplings prevent fits of dc
magnetization data, but in-phase alternating current susceptibility chi'MT data
down to 1.8 K indicate them to possess S = 4 ground states, if considered single
Mn16 units. If instead they are treated as tetramers of weakly coupled Mn4 units,
then each of the latter has an S = 2 ground state. Complexes 4 and 5 also exhibit
very weak out-of-phase chi"M signals characteristic of slow relaxation, and
magnetization versus dc field scans on a single crystal of 4.15MeCN at T >= 0.04
K showed hysteresis loops but with unusual features suggesting the magnetization
relaxation barrier consists of more than one contribution.
PMID- 27504744
TI - Face morphology: Can it tell us something about body weight and fat?
AB - This paper proposes a method for an automatic extraction of geometric features,
related to weight parameters, from 3D facial data acquired with low-cost depth
scanners. The novelty of the method relies both on the processing of the 3D
facial data and on the definition of the geometric features which are
conceptually simple, robust against noise and pose estimation errors,
computationally efficient, invariant with respect to rotation, translation, and
scale changes. Experimental results show that these measurements are highly
correlated with weight, BMI, and neck circumference, and well correlated with
waist and hip circumference, which are markers of central obesity. Therefore the
proposed method strongly supports the development of interactive, non obtrusive
systems able to provide a support for the detection of weight-related problems.
PMID- 27504745
TI - Using action research to build mentor capacity to improve orientation and quality
of nursing students' aged care placements: what to do when the phone rings.
AB - AIMS AND OBJECTIVES: To describe whether an action research approach can be used
to build capacity of residential aged care facility staff to support
undergraduate nursing students' clinical placements in residential aged care
facilities, using development of an orientation programme as an exemplar.
BACKGROUND: Aged care facilities are unpopular sites for nursing students'
clinical placements. A contributing factor is the limited capacity of staff to
provide students with a positive placement experience. Strategies to build mentor
capability to shape student placements and support learning and teaching are
critical if nursing students are to have positive placements that attract them to
aged care after graduation, an imperative given the increasing care needs of the
ageing population worldwide. DESIGN: Action research approach employing mixed
methods data collection (primarily qualitative with a quantitative component).
METHODS: Aged care facility staff (n = 32) formed a mentor group at each of two
Tasmanian facilities and met regularly to support undergraduate nursing students
(n = 40) during placements. Group members planned, enacted, reviewed and
reflected on orientation procedures to welcome students, familiarise them with
the facility and prepare them for their placement. Data comprised transcripts
from these and parallel student meetings, and orientation data from student
questionnaires from two successive placement periods (2011/2012). RESULTS:
Problems were identified in the orientation processes for the initial student
placements. Mentors implemented a revised orientation programme. Evaluation
demonstrated improved programme outcomes for students regarding knowledge of
facility operations, their responsibilities and emergency procedures. CONCLUSION:
Action research provides an effective approach to engage aged care facility staff
to build their capacity to support clinical placements. RELEVANCE TO CLINICAL
PRACTICE: Building capacity in the aged care workforce is vital to provide
appropriate care for residents with increasing care needs.
PMID- 27504746
TI - Covalent Conjugation of Small-Molecule Adjuvants to Nanoparticles Induces Robust
Cytotoxic T Cell Responses via DC Activation.
AB - Specific recognitions of pathogen associated molecular patterns by Toll-like
receptors (TLRs) initiate dendritic cell (DC) activation, which is critical for
coordinating innate and adaptive immune responses. Imidazoquinolines as small
molecule TLR7 agonists often suffer from prompt dissemination and short half-life
in the bloodstream, preventing their localization to the corresponding receptors
and effective DC activation. We postulated that covalent incorporation of
imidazoquinoline moieties onto the surface of biocompatible nanoparticles (~30 nm
size) would enhance their chemical stability, cellular uptake efficiency, and
adjuvanticity. The fully synthetic adjuvant-nanocomplexes led to successful DC
activation at lower nanomolar doses compared with free small-molecule agonists.
Once a model antigen such as ovalbumin was used for immunization, we found that
the nanocomplexes promoted an unusually strong cytotoxic T lymphocyte response,
revealing their unique immunostimulatory capacity benefiting from multivalency
and efficient transport to endosomal TLR7.
PMID- 27504747
TI - Clinician's Commentary on Morgan et al.(1).
PMID- 27504748
TI - Analysis of a Nitroreductase-Based Hypoxia Sensor in Primary Neuronal Cultures.
AB - The ability to assess oxygenation within living cells is much sought after to
more deeply understand normal and pathological cell biology. Hypoxia Red
manufactured by Enzo Life Sciences is advertised as a novel hypoxia detector
dependent on nitroreducatase activity. We sought to use Hypoxia Red in primary
neuronal cultures to test cell-to-cell metabolic variability in response to
hypoxic stress. Neurons treated with 90 min of hypoxia were labeled with Hypoxia
Red. We observed that, even under normoxic conditions neurons expressed
fluorescence robustly. Analysis of the chemical reactions and biological
underpinnings of this method revealed that the high uptake and reduction of the
dye is due to active nitroreductases in normoxic cells that are independent of
oxygen availability.
PMID- 27504749
TI - Radiation protection training for cardiologists in the era of multiple imaging
techniques and complex interventions.
AB - Cardiologists are among the heaviest medical users of ionising radiation. This
usage is growing in proportion to the expanding range of cardiac diagnostic tests
and interventional treatments. The primary focus of cardiologists is achieving
clear diagnoses as well as technically and clinically successful treatments. That
has to be set alongside strong awareness of the properties of ionising radiation
and associated safety issues. This article illustrates some of the interplay
between contemporary cardiology, radiological techniques, cardiology training and
ionising radiation regulations and aims to set context for training and
accreditation of cardiologists who use ionising radiation.
PMID- 27504750
TI - Families in the context of macroeconomic crises: A systematic review.
AB - The present study is a systematic review of empirical literature from the last 35
years on families' responses to economic distress in the context of macroeconomic
crises. Thirty-nine studies published between 1983 and 2015 in 12 countries were
identified, resulting in 3 main findings. First, economic distress was associated
with negative changes in family dynamics, specifically couple relationships and
parenting. Second, protective factors were found to buffer the adverse effects of
economic distress on family and individual outcomes. Third, the results suggest
that individual responses to macroeconomic crises may be moderated by sex.
Implications for future research encompass using validated assessment
instruments, including participants beyond 2-parent families with adolescent
children and conducting both longitudinal and qualitative studies that focus on
the processes and meanings of adaptation within this risk context. Conclusions
highlighted the need to assist families dealing with macroeconomic crises'
demands, encouraging the development and validation of macrosystemic intervention
programs. (PsycINFO Database Record
PMID- 27504751
TI - Randomized trial of parent training to prevent adolescent problem behaviors
during the high school transition.
AB - This randomized controlled trial tested a widely used general parent training
program, Common Sense Parenting (CSP), with low-income 8th graders and their
families to support a positive transition to high school. The program was tested
in its original 6-session format and in a modified format (CSP-Plus), which added
2 sessions that included adolescents. Over 2 annual cohorts, 321 families were
enrolled and randomly assigned to either the CSP, CSP-Plus, or minimal-contact
control condition. Pretest, posttest, 1-year follow-up, and 2-year follow-up
survey data on parenting as well as youth school bonding, social skills, and
problem behaviors were collected from parents and youth (94% retention).
Extending prior examinations of posttest outcomes, intent-to-treat regression
analyses tested for intervention effects at the 2 follow-up assessments, and
growth curve analyses examined experimental condition differences in yearly
change across time. Separate exploratory tests of moderation by youth gender,
youth conduct problems, and family economic hardship also were conducted. Out of
52 regression models predicting 1- and 2-year follow-up outcomes, only 2 out of
104 possible intervention effects were statistically significant. No
statistically significant intervention effects were found in the growth curve
analyses. Tests of moderation also showed few statistically significant effects.
Because CSP already is in widespread use, findings have direct implications for
practice. Specifically, findings suggest that the program may not be efficacious
with parents of adolescents in a selective prevention context and may reveal the
limits of brief, general parent training for achieving outcomes with parents of
adolescents. (PsycINFO Database Record
PMID- 27504752
TI - Mexican-origin parents' differential treatment and siblings' adjustment from
adolescence to young adulthood.
AB - Parents' differential treatment is a common family dynamic that has been linked
to youth's well-being in childhood and adolescence in European American families.
Much less is known, however, about this family process in other ethnic groups.
The authors examined the longitudinal associations between parents' differential
treatment (PDT) and both depressive symptoms and risky behaviors of Mexican
origin sibling pairs from early adolescence through young adulthood. They also
tested the moderating roles of cultural orientations as well as youth age, gender
and sibling dyad gender constellation in these associations. Participants were
mothers, fathers, and 2 siblings from 246 Mexican-origin families who
participated in individual home interviews on 3 occasions over 8 years.
Multilevel models revealed that, controlling for dyadic parent-child relationship
qualities (i.e., absolute levels of warmth and conflict), adolescents who had
less favorable treatment by mothers relative to their sibling reported more
depressive symptoms and risky behavior, on average. Findings for fathers' PDT
emerged at the within-person level indicating that, on occasions when adolescents
experienced less favorable treatment by fathers than usual, they reported more
depressive symptoms and risky behavior. However, some of these effects were
moderated by youth age and cultural socialization. For example, adolescents who
experienced relatively less paternal warmth than their siblings also reported
poorer adjustment, but this effect did not emerge for young adults; such an
effect also was significant for unfavored youth with stronger but not weaker
cultural orientations. (PsycINFO Database Record
PMID- 27504753
TI - Parents behaving badly: Gender biases in the perception of parental alienating
behaviors.
AB - According to gender role theory, individuals who confirm expectations associated
with their gender roles are rewarded and judged against these expectations when
they deviate. Parental roles are strongly tied to gender, and there are very
different expectations for behaviors of mothers and fathers. This study examined
how mothers' and fathers' behaviors that support or discourage a positive
relationship with the other parent are perceived in terms of their acceptability.
Two-hundred twenty-eight parents completed an online survey assessing perceptions
of acceptability of negative (parental alienating) and positive coparenting
behaviors. Results provided support for our hypothesis: Although parental
alienating behaviors were rated unacceptable, they were more acceptable for
mothers than fathers. Expectancy violation theory can explain why parental
alienating behaviors are not viewed as negatively when mothers exhibit them than
fathers. (PsycINFO Database Record
PMID- 27504754
TI - Daily patterns of stress and conflict in couples: Associations with marital
aggression and family-of-origin aggression.
AB - For many married individuals, the ups and downs of daily life are connected such
that stressors impacting one person also impact the other person. For example,
stress experienced by one individual may "spill over" to negatively impact
marital functioning. This study used both partners' daily diary data to examine
same-day and cross-day links between stress and marital conflict and tested
several factors that make couples vulnerable to spillover. Assessment of 25 wide
ranging sources of daily stress included both paid and unpaid work, health
issues, financial concerns, and having to make difficult decisions. Results
showed that both husbands' and wives' experiences of total daily stress were
associated with greater same-day marital conflict and that conflict was greater
on days both spouses experienced high levels of stress. Evidence of cross-day
spillover was found only in those couples with high concurrent marital aggression
and in couples where wives reported high family-of-origin aggression. These
results highlight both the common, anticipated nature of same-day spillover and
the potentially problematic aspects of more prolonged patterns representing
failure to recover from stressors that occurred the previous day. The discussion
focuses on how reactivity in one life domain puts that individual at risk for
generating stress in another life domain and how current marital aggression and
family-of-origin aggression are associated with difficulty recovering from
stressful events. (PsycINFO Database Record
PMID- 27504756
TI - What Brexit means for biotech.
PMID- 27504757
TI - 'Brexit' stuns UK biotech into waiting game, but not all signals are red.
PMID- 27504755
TI - Large-Conductance Transmembrane Porin Made from DNA Origami.
AB - DNA nanotechnology allows for the creation of three-dimensional structures at
nanometer scale. Here, we use DNA to build the largest synthetic pore in a lipid
membrane to date, approaching the dimensions of the nuclear pore complex and
increasing the pore-area and the conductance 10-fold compared to previous man
made channels. In our design, 19 cholesterol tags anchor a megadalton funnel
shaped DNA origami porin in a lipid bilayer membrane. Confocal imaging and ionic
current recordings reveal spontaneous insertion of the DNA porin into the lipid
membrane, creating a transmembrane pore of tens of nanosiemens conductance. All
atom molecular dynamics simulations characterize the conductance mechanism at the
atomic level and independently confirm the DNA porins' large ionic conductance.
PMID- 27504758
TI - Genentech's PD-L1 agent approved for bladder cancer.
PMID- 27504759
TI - Biogen and UPenn join forces to commercialize gene therapies.
PMID- 27504760
TI - Juno's wild ride.
PMID- 27504761
TI - Cancer anabolic metabolism inhibitors move into clinic.
PMID- 27504762
TI - First-in-human CRISPR trial.
PMID- 27504763
TI - Synthetic human genome set to spur applications.
PMID- 27504764
TI - Gilead's first pan-genotypic HCV cure.
PMID- 27504765
TI - Around the world in a month.
PMID- 27504766
TI - Drug pipeline: 2Q16.
PMID- 27504767
TI - 2Q16-biotech claws back.
PMID- 27504768
TI - Research biotech patenting 2015.
PMID- 27504769
TI - First Rounders Podcast: David Baltimore.
PMID- 27504770
TI - Nanopore development at Oxford Nanopore.
PMID- 27504771
TI - Rapid, semi-automated protein terminal characterization using ISDetect.
PMID- 27504773
TI - Recent patents in synthetic biology.
PMID- 27504772
TI - The rise and fall of innovation in biofuels.
PMID- 27504774
TI - Deep phenotyping predicts Huntington's genotype.
PMID- 27504775
TI - An edible switch for gene therapy.
PMID- 27504776
TI - Automated design of DNA origami.
PMID- 27504779
TI - Erratum: No longer going to waste.
PMID- 27504780
TI - Erratum: Near-optimal probabilistic RNA-seq quantification.
PMID- 27504781
TI - Erratum: Genome-wide analysis reveals specificities of Cpf1 endonucleases in
human cells.
PMID- 27504782
TI - Erratum: Nature Biotechnology's academic spinouts of 2015.
PMID- 27504778
TI - Sharing and community curation of mass spectrometry data with Global Natural
Products Social Molecular Networking.
AB - The potential of the diverse chemistries present in natural products (NP) for
biotechnology and medicine remains untapped because NP databases are not
searchable with raw data and the NP community has no way to share data other than
in published papers. Although mass spectrometry (MS) techniques are well-suited
to high-throughput characterization of NP, there is a pressing need for an
infrastructure to enable sharing and curation of data. We present Global Natural
Products Social Molecular Networking (GNPS; http://gnps.ucsd.edu), an open-access
knowledge base for community-wide organization and sharing of raw, processed or
identified tandem mass (MS/MS) spectrometry data. In GNPS, crowdsourced curation
of freely available community-wide reference MS libraries will underpin improved
annotations. Data-driven social-networking should facilitate identification of
spectra and foster collaborations. We also introduce the concept of 'living data'
through continuous reanalysis of deposited data.
PMID- 27504783
TI - Second-quarter biotech job picture.
PMID- 27504785
TI - Branching Ratios and Vibrational Distributions in Water-Forming Reactions of OH
and OD Radicals with Methylamines.
AB - Reactions of OH and OD radicals with (CH3)3N, (CH3)2NH, and CH3NH2 were studied
by Fourier transform infrared emission spectroscopy (FTIR) of the water product
molecules from a fast-flow reactor at 298 K. The rate constants (4.4 +/- 0.5) *
10(-11), (5.2 +/- 0.8) * 10(-11), and (2.0 +/- 0.4) * 10(-11) cm(3) molecule(-1)
s(-1) were determined for OD + (CH3)3N, (CH3)2NH, and CH3NH2, respectively, by
comparing the HOD emission intensities to the HOD intensity from the OD reaction
with H2S. Abstraction from the nitrogen site competes with abstraction from the
methyl group, as obtained from an analysis of the HOD and D2O emission
intensities from the OD reactions with the deuterated reactants, (CD3)2NH and
CD3NH2. After adjustment for the hydrogen-deuterium kinetic isotope effect, the
product branching fractions of the hydrogen abstraction from the nitrogen for di-
and monomethylamine were found to be 0.34 +/- 0.04 and 0.26 +/- 0.05,
respectively. Vibrational distributions of the H2O, HOD, and D2O molecules are
typical for direct hydrogen atom abstraction from polar molecules, even though
activation energies are negative because of the formation of pre-transition-state
complexes. Comparison is made to the reactions of hydroxyl radicals with ammonia
and with other compounds with primary C-H bonds to discuss specific features of
disposal of energy to water product.
PMID- 27504787
TI - Store-Operated Ca2+ Entry in Oocytes Modulate the Dynamics of IP3 -Dependent Ca2+
Release From Oscillatory to Tonic.
AB - Ca2+ signaling is ubiquitous and mediates various cellular functions encoded in
its spatial, temporal, and amplitude features. Here, we investigate the role of
store-operated Ca2+ entry (SOCE) in regulating the temporal dynamics of Ca2+
signals in Xenopus oocytes, which can be either oscillatory or tonic. Oscillatory
Ca2+ release from intracellular stores is typically observed at physiological
agonist concentration. When Ca2+ release leads to Ca2+ store depletion, this
triggers the activation of SOCE that translates into a low-amplitude tonic Ca2+
signal. SOCE has also been implicated in fueling Ca2+ oscillations when activated
at low levels. Here, we show that sustained SOCE activation in the presence of
IP3 to gate IP3 receptors (IP3 R) results in a pump-leak steady state across the
endoplasmic reticulum (ER) membrane that inhibits Ca2+ oscillations and produces
a tonic Ca2+ signal. Tonic signaling downstream of SOCE activation relies on
focal Ca2+ entry through SOCE ER-plasma membrane (PM) junctions, Ca2+ uptake into
the ER, followed by release through open IP3 Rs at distant sites, a process we
refer to as "Ca2+ teleporting." Therefore, sustained SOCE activation in the
presence of an IP3 -dependent "leak" pathway at the ER membrane results in a
switch from oscillatory to tonic Ca2+ signaling. J. Cell. Physiol. 232: 1095
1103, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27504786
TI - Structural Characterization of Serum N-Glycans by Methylamidation, Fluorescent
Labeling, and Analysis by Microchip Electrophoresis.
AB - To characterize the structures of N-glycans derived from human serum, we report a
strategy that combines microchip electrophoresis, standard addition, enzymatic
digestion, and matrix-assisted laser desorption/ionization-mass spectrometry
(MALDI-MS). We compared (i) electrophoretic mobilities of known N-glycans from
well-characterized (standard) glycoproteins through standard addition, (ii) the
electrophoretic mobilities of N-glycans with their molecular weights determined
by MALDI-MS, and (iii) electrophoretic profiles of N-glycans enzymatically
treated with fucosidase. The key step to identify the sialylated N-glycans was to
quantitatively neutralize the negative charge on both alpha2,3- and alpha2,6
linked sialic acids by covalent derivatization with methylamine. Both neutralized
and nonsialylated N-glycans from these samples were then reacted with 8
aminopyrene-1,3,6-trisulfonic acid (APTS) to provide a fluorescent label and a
triple-negative charge, separated by microchip electrophoresis, and detected by
laser-induced fluorescence. The methylamidation step leads to a 24% increase in
the peak capacity of the separation and direct correlation of electrophoretic and
MALDI-MS results. In total, 37 unique N-glycan structures were assigned to 52
different peaks recorded in the electropherograms of the serum samples. This
strategy ensures the needed separation efficiency and detectability, easily
resolves linkage and positional glycan isomers, and is highly reproducible.
PMID- 27504788
TI - Transition-Metal-Free Diastereoselective Epoxidation of Trifluoromethylketones
with N-Tosylhydrazones: Access to Tetrasubstituted Trifluoromethylated Oxiranes.
AB - The first example of the epoxidation reaction of trifluoromethylketones with N
tosylhydrazones under transition-metal free conditions is reported. This
epoxidation reaction provided tetrasubstituted trifluoromethylated oxiranes with
excellent yields and diastereoselectivities. The salient features of this
reaction include readily available starting materials, mild conditions, broad
substrate scope, high efficiency, and valuable further applications. Remarkably,
this reaction proceeded through an unprecedented nucleophilic addition process,
and the ammonium O-anion intermediate was detected and characterized by NMR and
HRMS analysis.
PMID- 27504790
TI - Synthesis of l-Pyranosides by Hydroboration of Hex-5-enopyranosides Revisited.
AB - Extensive study of the diastereoselective synthesis of l-pyranosides utilizing
hydroboration of substituted exo-glucals (5-enopyranosides) obtained from d
sugars is presented. On the basis of this study we present the empirical rules
describing the reaction stereoselectivity and the correlation between the yield
of the l-ido product and the size of protecting groups used. Application of these
guidelines revealed that the hydroboration of methyl 2,3-O-methyl-6-deoxy-alpha-d
xylo-hex-5-enopyranoside resulted in exclusive formation of l-ido product with
high yield. This method can be successfully applied to the synthesis of l
iduronic acid being an essential component of anticoagulant drugs with
diastereoselectivity superior to previously published protocols.
PMID- 27504789
TI - An old culprit but a new story: bisphenol A and "NextGen" bisphenols.
AB - The concept that developmental events shape adult health and disease was sparked
by the recognition of a link between maternal undernutrition and coronary disease
in adults. From that beginning, a new field-the developmental origins of health
and disease-emerged, and attention has focused on the effects of a wide array of
developmental perturbations. Exposure to endocrine-disrupting chemicals has been
of particular interest, and a ubiquitous environmental contaminant bisphenol A
(BPA) has become the endocrine-disrupting chemical poster child. Bisphenol A has
been the subject of intense investigation for nearly two decades, and exposure
effects have been described in hundreds of experimental, epidemiological, and
clinical studies. From the standpoint of reproductive health, the findings are
particularly important, as they suggest that the ovary, testis, and reproductive
tract in both sexes are targets of BPA action. The findings and the media and
regulatory attention garnered by them have generated increasing public concern
and resulted in legislative bans on BPA in some countries. The subsequent
introduction of BPA-free products, although a masterful marketing strategy, is in
reality only the beginning of a new and complex chapter of the BPA story. In this
review we attempt to summarize what we have learned about the reproductive
effects of BPA, present the reasons why studying the effects of this chemical in
humans is no longer sufficient, and outline the challenges that the growing array
of next generation bisphenols represents to clinicians, researchers, federal
agencies, and the general public.
PMID- 27504791
TI - Analysis of melamine in milk powder by using a magnetic molecularly imprinted
polymer based on carbon nanotubes with ultra high performance liquid
chromatography and tandem mass spectrometry.
AB - A new magnetic molecularly imprinted polymer was coupled with ultra high
performance liquid chromatography and tandem mass spectrometry for the selective
determination of melamine in milk powder. The magnetic molecularly imprinted
polymer has been prepared by using carbon nanotubes as the matrix, Fe3 O4
particles as the magnetic ingredient, melamine as the template molecule,
methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the
cross-linker and polyvinylpyrrolidone as the dispersant. The polymer was
characterized with scanning electron microscopy, Fourier transform infrared
spectroscopy and a physical property measurement system. The isothermal
adsorption, kinetics adsorption, and selectivity were studied to evaluate the
rebinding properties of the magnetic molecularly imprinted polymer. Various
parameters affecting the extraction efficiency such as the amount of polymer,
extraction time, and eluting solution were evaluated. The limit of detection was
0.00075 mg/kg. The relative standard deviations of the intraday and interday
precision are 0.4-2.7 and 2.3-5.1%, respectively. The proposed method was
successfully applied to determine melamine in different milk powder samples from
different provenances, and satisfactory recoveries of 89.0-95.6% were obtained.
This method has great significance for quality control and is simple and suitable
for the rapid determination of melamine in milk powder.
PMID- 27504792
TI - Printed organo-functionalized graphene for biosensing applications.
AB - Graphene is a highly promising material for biosensors due to its excellent
physical and chemical properties which facilitate electron transfer between the
active locales of enzymes or other biomaterials and a transducer surface.
Printing technology has recently emerged as a low-cost and practical method for
fabrication of flexible and disposable electronics devices. The combination of
these technologies is promising for the production and commercialization of low
cost sensors. In this review, recent developments in organo-functionalized
graphene and printed biosensor technologies are comprehensively covered. Firstly,
various methods for printing graphene-based fluids on different substrates are
discussed. Secondly, different graphene-based ink materials and preparation
methods are described. Lastly, biosensing performances of printed or printable
graphene-based electrochemical and field effect transistor sensors for some
important analytes are elaborated. The reported printed graphene based sensors
exhibit promising properties with good reliability suitable for commercial
applications. Among most reports, only a few printed graphene-based biosensors
including screen-printed oxidase-functionalized graphene biosensor have been
demonstrated. The technology is still at early stage but rapidly growing and will
earn great attention in the near future due to increasing demand of low-cost and
disposable biosensors.
PMID- 27504793
TI - CdTe/CdSe quantum dot-based fluorescent aptasensor with hemin/G-quadruplex DNzyme
for sensitive detection of lysozyme using rolling circle amplification and strand
hybridization.
AB - Lysozyme with a small monomeric globular enzymatic protein is part of the innate
immune system, and its deficiency can cause the increased incidence of disease.
Herein, we devise a new signal-enhanced fluorescence aptasensing platform for
quantitative screening of lysozyme by coupling with rolling circle amplification
(RCA) and strand hybridization reaction, accompanying the assembly of CdTe/CdSe
quantum dots (QDs) and hemin/G-quadruplex DNzyme. Initially, target-triggered
release of the primer was carried out from DNA duplex via the reaction of the
aptamer with the analyte, and the released primer could be then utilized as the
template to produce numerous repeated oligonucleotide sequences by the RCA
reaction. Following that, the formed long-stranded DNA simultaneously hybridized
with the CdTe/CdSe QD-labeled probe and hemin/G-quadruplex DNzyme strand in the
system, thereby resulting in the quenching of QD fluorescent signal through the
proximity hemin/G-quadruplex DNzyme on the basis of transferring photoexcited
conduction band electrons of quantum dots to Fe(III)/Fe(II)-protoporphyrin IX
(hemin) complex. Under optimal conditions, the fluorescent signal decreased with
the increasing target lysozyme within the dynamic range from 5.0 to 500nM with a
detection limit (LOD) of 2.6nM at the 3sblank criterion. Intra-assay and
interassay coefficients of variation (CVs) were below 8.5% and 11.5%,
respectively. Finally, the system was applied to analyze spiked human serum
samples, and the recoveries in all cases were 85-111.9%.
PMID- 27504794
TI - Adverse Reactions to Gadoterate Meglumine: Review of Over 25 Years of Clinical
Use and More Than 50 Million Doses.
AB - OBJECTIVE: The aim of this study was to evaluate the safety profile of gadoterate
meglumine from clinical trials, postmarketing observational studies, and
pharmacovigilance reports of adverse drug reactions (ADRs) encompassing 25 years
of clinical use and over 50 million administered doses. MATERIALS AND METHODS:
Assessment of the safety of gadoterate meglumine through processing and review of
all safety data was collected after magnetic resonance imaging procedures. All
ADRs originated from 3 major sources: (1) a clinical study database including 50
phase I to IV studies involving 2822 patients, (2) a safety database including 8
postmarketing safety studies (PMSs) involving 151,050 patients, and (3) a
pharmacovigilance database compiling safety experience following over 50 million
doses administered between March 1989 and September 2015. RESULTS: Among the 2822
patients receiving gadoterate meglumine in the clinical trials, 241 (8.5%)
experienced 405 postinjection adverse events (AEs), considered related to the
contrast agent for 113 patients (4.0%). Serious AEs were reported for 27 patients
(1.0%) and assessed as related to gadoterate meglumine for 2 patients (0.07%).
None of the PMS studies showed evidence of unexpected safety issues, with a very
low rate of AEs (<1%). Postmarketing safety experience with over 50 million doses
of gadoterate meglumine prescribed for 25 years of approved use worldwide
compiled spontaneous reports for 3797 patients who experienced 8397 ADRs,
yielding a very low reported incidence of ADRs of 0.007% of patients. There was
no single-agent case of confirmed nephrogenic systemic fibrosis with gadoterate
meglumine either from clinical development programs or from postmarketing
experience. CONCLUSIONS: Based on clinical trials, postmarketing observational
studies and pharmacovigilance data, a very low incidence of ADRs was reported
with gadoterate meglumine, which has no impact on its favourable benefit-risk
ratio.
PMID- 27504795
TI - Temporal Changes of Texture Features Extracted From Pulmonary Nodules on Dynamic
Contrast-Enhanced Chest Computed Tomography: How Influential Is the Scan Delay?
AB - OBJECTIVES: The aim of this study was to describe the temporal changes of various
texture features extracted from pulmonary nodules on dynamic contrast-enhanced
computed tomography (DCE-CT) and to compare the feature values among multiple
scanning time points. We also aimed to analyze the variability of texture
features across multiple scan delay times. MATERIALS AND METHODS: This
retrospective study was approved by the institutional review board of Seoul
National University Hospital with waiver of patients' informed consent. Twenty
patients (M:F, 6:14; mean age, 60.25 +/- 11.97 years) with 20 lung nodules (mean
size, 24.1 +/- 12.3 mm) underwent DCE-CT with multiple scan delays (30, 60, 90,
120, 150, 180, 210, 240, 300, and 480 seconds) after precontrast scans. Lung
nodule segmentation and texture feature extraction were performed at each time
point using in-house software. Texture feature values were compared among the
multiple time points using the Friedman test with post hoc pairwise Wilcoxon
signed rank test. In addition, the dynamic range (DR) reflecting the variability
between 2 time points to the interpatient range was calculated. Thereafter, we
determined the stable time range that met both "DR greater than 0.90" and "no
statistically significant difference" between all time point pairs for each
feature. The degree of variability across all scan delay times was obtained using
coefficients of variation. RESULTS: Standard deviation, variance, entropy,
sphericity, discrete compactness, gray-level cooccurrence matrix (GLCM) inverse
difference moment (IDM), GLCM contrast, and GLCM entropy did not show significant
differences between scan delays of 30 and 180 seconds with DR greater than 0.90
between all time point pairs. When the range was narrowed down to 60 to 150
seconds, an additional 2 values (mean and homogeneity) showed stability. Among
the 13 texture features, entropy, sphericity, discrete compactness, and GLCM
entropy exhibited the lowest variability (coefficient of variation <=5%).
CONCLUSIONS: Most texture features exhibited stability with low variation between
60 and 150 seconds on DCE-CT. Thus, texture features extracted from contrast
enhanced CT with a scan delay range of 60 to 150 seconds can be used for tumor
characterization despite the heterogeneity in delay time.
PMID- 27504796
TI - Multifrequency Magnetic Resonance Elastography for the Assessment of Renal
Allograft Function.
AB - OBJECTIVE: The aim of this study was to apply multifrequency magnetic resonance
elastography (MMRE) for assessment of kidney function based on renal stiffness of
allografts in transplant recipients and native kidneys in controls. METHODS: In
this prospective study, MMRE was used to measure stiffness in transplant kidneys
in 22 recipients (age range, 23-73 years; 7 females) and in native kidneys in 11
controls (age range, 26-55 years; 4 females) after internal review board
approval. The MMRE was performed on a 1.5 T magnetic resonance imaging scanner
using 4 vibration frequencies from 40 to 70 Hz. Stiffness maps were computed by
multifrequency reconstruction of the magnitude shear modulus (|G*|). Clinical
markers such as glomerular filtration rate (GFR) and resistive index (RI) were
acquired. Differences in renal stiffness among groups were compared by Mann
Whitney U test. Correlations were tested using Pearson correlation. RESULTS:
Functioning transplants had higher stiffness (|G*| = 9.00 +/- 1.71 kPa) than
nonfunctioning transplants (|G*| = 5.88 +/- 1.71 kPa, P < 0.001) and native
kidneys (|G*| = 6.63 +/- 1.63 kPa, P < 0.01). A cutoff value of 7.04 kPa provided
sensitivity (83.33%) and specificity (86.67%) for detecting renal allograft
dysfunction with an area under the receiver operating characteristic curve value
of 0.9278 (95% confidence interval, 0.83-1.00). |G*| correlated positively with
GFR (r = 0.52, P = 0.015) and negatively with RI (r = -0.52, P = 0.016).
CONCLUSIONS: Multifrequency magnetic resonance elastography has good diagnostic
accuracy in detecting renal allograft dysfunction. Renal stiffness is
significantly lower in recipients with nonfunctioning transplant kidneys and
correlates with clinical markers such as GFR and RI.
PMID- 27504797
TI - Exploring the association of ego defense mechanisms with problematic internet use
in a Pakistani medical school.
AB - The present study was designed to analyze association between problematic
internet use and use of ego defense mechanisms in medical students. This cross
sectional study was undertaken at CMH Lahore Medical College (CMH LMC) in Lahore,
Pakistan from 1st March, 2015 to 30th May, 2015. 522 medical and dental students
were included in the study. The questionnaire consisted of three sections: a)
demographic characteristics of respondent b) the Defense Style Questionnaire-40
(DSQ-40) and c) the Internet Addiction Test (IAT). All data were analyzed in SPSS
v20. Chi square, Independent sample t test and One Way ANOVA were run to analyze
association of different variables with scores on IAT. Multiple regression
analysis was used to delineate ego defenses as predictors of problematic internet
use. A total of 32 (6.1%) students reported severe problems with internet usage.
Males had higher scores on IAT i.e had more problematic use of internet. Scores
on internet addiction test (IAT) were negatively associated with sublimation and
positively associated with projection, denial, autistic fantasy, passive
aggression and displacement. There was a high prevalence of problematic use of
internet among medical and dental students. It had significant associations with
several defense mechanisms.
PMID- 27504798
TI - Regional Intestinal Permeability of Three Model Drugs in Human.
AB - Currently there are only a limited number of determinations of human Peff in the
distal small intestine and none in the large intestine. This has hindered the
validation of preclinical models with regard to absorption in the distal parts of
the intestinal tract, which can be substantial for BCS class II-IV drugs, and
drugs formulated into modified-release (MR) dosage forms. To meet this demand,
three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution
intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers.
The Peff of each model drug was then calculated using a validated deconvolution
method. The median Peff of atenolol in the jejunum, ileum, and colon was 0.45,
0.15, and 0.013 * 10(-4) cm/s, respectively. The corresponding values for
metoprolol were 1.72, 0.72, and 1.30 * 10(-4) cm/s, and for ketoprofen 8.85,
6.53, and 3.37 * 10(-4) cm/s, respectively. This is the first study where the
human Peff of model drugs has been determined in all parts of the human
intestinal tract in the same subjects. The jejunal values were similar to
directly determined values using intestinal single-pass perfusion, indicating
that the deconvolution method is a valid approach for determining regional Peff.
The values from this study will be highly useful in the validation of preclinical
regional absorption models and in silico tools.
PMID- 27504800
TI - Osteopontin Blockade Attenuates Renal Injury After Ischemia Reperfusion by
Inhibiting NK Cell Infiltration.
AB - Renal ischemia-reperfusion (RIR) injury is a common occurrence after major
surgery and shock, leading to acute kidney injury (AKI). Osteopontin (OPN) is a
secreted glycoprotein that acts as a proinflammatory cytokine and activator of T
lymphocytes. We hypothesized that blockade of OPN reduces the severity of
inflammation and injury in RIR. Renal ischemia was induced in adult C57BL/6 mice
via bilateral clamping of renal pedicles for 35 min, followed by reperfusion for
24 h. Anti-OPN antibody (Ab), nonimmunized isotype immunoglobulin G, or normal
saline was injected intravenously at the time of reperfusion. Blood and kidneys
were collected for analysis. At 24 h after RIR, OPN mRNA and protein levels were
significantly increased in renal tissue compared with sham mice. In serum,
elevated levels of blood urea nitrogen and creatinine were reduced in anti-OPN Ab
treated mice compared with vehicle. Anti-OPN Ab-treated mice also had decreased
mRNA levels of injury markers neutrophil gelatinase-associated lipocalin and
kidney injury molecule-1 compared with the vehicle. The histologic architecture
and apoptosis of renal tissue were improved in the anti-OPN Ab-treated mice. In
renal tissue, inflammatory cytokines interleukin 6 and tumor necrosis factor
alpha protein levels were reduced in the Ab-treated mice. Natural killer (NK)
cell infiltration was decreased after anti-OPN Ab treatment, as was neutrophil
infiltration, shown by reduced chemokine expression and Gr1 renal
immunohistochemical staining. These findings demonstrate a beneficial role of OPN
blockade in RIR associated with NK cell-mediated downregulation of inflammatory
cytokines and chemokines. Administration of anti-OPN Ab may therefore serve as an
immunomodulatory adjunct in the treatment of RIR-induced AKI.
PMID- 27504801
TI - Mean Platelet Volume to Platelet Count Ratio as a Promising Predictor of Early
Mortality in Severe Sepsis.
AB - PURPOSE: We evaluated the mean platelet volume (MPV) to platelet ratio to
determine its significance as a prognostic marker for early mortality in
critically ill patients with suspected sepsis receiving early goal-directed
therapy (EGDT). METHODS: We retrospectively reviewed the records from a
prospective EGDT registry and screened eligible adult patients who were admitted
to the emergency department (ED) with severe sepsis and/or septic shock. The
MPV/platelet ratio was estimated as the MPV value divided by the platelet count
on each day of hospitalization. The clinical outcome was 28-day mortality.
RESULTS: We included 120 patients receiving EGDT. In the multivariate Cox
proportional hazard models, higher MPV/platelet ratios on admission (HR: 1.04;
95% CI: 1.015-1.066; P = 0.002) and at 24 h (HR: 1.032; 95% CI: 1.012-1.054; P =
0.002) were significant risk factors for mortality at 28 days. An increased trend
for 28-day mortality was associated with a MPV/platelet ratio >3.71 on admission
(HR: 4.274; 95% CI: 1.228-14.874; P = 0.023) and a higher MPV/platelet ratio
(>6.49) at 24 h (HR: 2.719; 95% CI: 1.048-7.051; P = 0.04) in patients with
severe sepsis receiving EGDT. CONCLUSION: In our study, MPV or platelet count
alone did not predict shock and 28-day mortality in patients with severe sepsis
receiving EGDT. However, the MPV/platelet ratio at ED admission and on day 1 is a
promising prognostic marker for 28-day mortality in patients with severe sepsis.
PMID- 27504802
TI - alpha-Lactose Improves the Survival of Septic Mice by Blockade of TIM-3 Signaling
to Prevent NKT Cell Apoptosis and Attenuate Cytokine Storm.
AB - Sepsis is the leading cause of death among critically ill patients and natural
killer T (NKT) cell activation is essential to induce inflammatory cytokine
cascade in sepsis. However, little is known about what regulates the NKT cell
function during sepsis. Herein, we showed that T-cell immunoglobulin and mucin
domain 3 (Tim-3) expression in NKT cells is elevated in experimental mice during
sepsis. Tim-3 expression was positively correlated with NKT cell activation and
apoptosis. In sepsis, interleukin (IL)-12 secreted by dendritic cell exposure to
lipopolysaccharide increased the expression of Tim-3 in NKT cells. Administration
of alpha-lactose to block Tim-3 signaling pathway significantly improved the
survival of septic mice, concomitant with reduced IL-12 production by dendritic
cells, reduced Tim-3 expression, prevented NKT cell apoptosis, and attenuated
production of inflammatory cytokines. Collectively, Tim-3 signaling in NKT cells
plays a critical role in the immunopathogenesis of sepsis. Thus, alpha-lactose
could be a promising immunomodulatory agent in the treatment of sepsis.
PMID- 27504803
TI - Coarse-Grained Molecular Dynamics Study of the Curing and Properties of Highly
Cross-Linked Epoxy Polymers.
AB - In this work, a coarse-grained model is developed for highly cross-linked
bisphenol A diglycidyl ether epoxy resin with diaminobutane hardener. In this
model, all conformationally relevant coarse-grained degrees of freedom are
accounted for by sampling over the free-energy surfaces of the atomic structures
using quantum mechanical simulations. The interaction potentials between
nonbonded coarse-grained particles are optimized to accurately predict the
experimentally measured density and glass-transition temperature of the system.
In addition, a new curing algorithm is also developed to model the creation of
highly cross-linked epoxy networks. In this algorithm, to create a highly cross
linked network, the reactants are redistributed from regions with an excessive
number of reactive molecules to regions with a lower number of reactants to
increase the chances of cross-linking. This new algorithm also dynamically
controls the rate of cross-linking at each local region to ensure uniformity of
the resulting network. The curing simulation conducted using this algorithm is
able to develop polymeric networks having a higher average degree of cross
linking, which is more uniform throughout the simulation cell as compared to that
in the networks cured using other curing algorithms. The predicted gel point from
the current curing algorithm is in the acceptable theoretical and experimental
range of measured values. Also, the resulting cross-linked microstructure shows a
volume shrinkage of 5%, which is close to the experimentally measured volume
shrinkage of the cured epoxy. Finally, the thermal expansion coefficients of
materials in the glassy and rubbery states show good agreement with the
experimental values.
PMID- 27504804
TI - Metal and Metalloid Size-Fractionation Strategies in Spatial High-Resolution
Sediment Pore Water Profiles.
AB - Sediment water interfaces (SWIs) are often characterized by steep biogeochemical
gradients determining the fate of inorganic and organic substances. Important
transport processes at the SWI are sedimentation and resuspension of particulate
matter and fluxes of dissolved materials. A microprofiling and micro sampling
system (missy), enabling high resolution measurements of sediment parameters in
parallel to a direct sampling of sediment pore waters (SPWs), was combined with
two fractionation approaches (ultrafiltration (UF) and cloud point extraction
(CPE)) to differentiate between colloidal and dissolved fractions at a millimeter
scale. An inductively coupled plasma-quadrupole mass spectrometry method
established for volumes of 300 MUL enabled the combination of the high resolution
fractionation with multi-element analyzes. UF and CPE comparably indicated that
manganese is predominantly present in dissolved fractions of SPW profiles.
Differences found for cobalt and iron showed that the results obtained by size
dependent UF and micelle-mediated CPE do not necessarily coincide, probably due
to different fractionation mechanisms. Both methods were identified as suitable
for investigating fraction-related element concentrations in SPW along sediment
depth profiles at a millimeter scale. The two approaches are discussed with
regard to their advantages, limitations, potential sources of errors, further
improvements, and potential future applications.
PMID- 27504805
TI - The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors
and induces cortical folding in mice.
AB - Cortical expansion and folding are often linked to the evolution of higher
intelligence, but molecular and cellular mechanisms underlying cortical folding
remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental
duplications during hominoid evolution, but its role in brain development has not
been explored. Here, we found that expression of TBC1D3 in ventricular cortical
progenitors of mice via in utero electroporation caused delamination of
ventricular radial glia cells (vRGs) and promoted generation of self-renewing
basal progenitors with typical morphology of outer radial glia (oRG), which are
most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured
human brain slices decreased generation of oRGs. Interestingly, localized oRG
proliferation resulting from either in utero electroporation or transgenic
expression of TBC1D3, was often found to underlie cortical regions exhibiting
folding. Thus, we have identified a hominoid gene that is required for oRG
generation in regulating the cortical expansion and folding.
PMID- 27504806
TI - Adaptive learning and decision-making under uncertainty by metaplastic synapses
guided by a surprise detection system.
AB - Recent experiments have shown that animals and humans have a remarkable ability
to adapt their learning rate according to the volatility of the environment. Yet
the neural mechanism responsible for such adaptive learning has remained unclear.
To fill this gap, we investigated a biophysically inspired, metaplastic synaptic
model within the context of a well-studied decision-making network, in which
synapses can change their rate of plasticity in addition to their efficacy
according to a reward-based learning rule. We found that our model, which assumes
that synaptic plasticity is guided by a novel surprise detection system, captures
a wide range of key experimental findings and performs as well as a Bayes optimal
model, with remarkably little parameter tuning. Our results further demonstrate
the computational power of synaptic plasticity, and provide insights into the
circuit-level computation which underlies adaptive decision-making.
PMID- 27504808
TI - Primary Neuroendocrine Carcinoma of the Kidney on FDG PET/CT.
AB - A 28-year-old woman presented gradually worsening intermittent right groin pain
for 10 months. FDG PET/CT was performed to evaluate the suspected renal
malignancy. The images demonstrated a large hypermetabolic tumor occupying the
entire right kidney. Pathological examination demonstrated a primary
neuroendocrine carcinoma of the kidney.
PMID- 27504807
TI - Suppression of ischemia in arterial occlusive disease by JNK-promoted native
collateral artery development.
AB - Arterial occlusive diseases are major causes of morbidity and mortality. Blood
flow to the affected tissue must be restored quickly if viability and function
are to be preserved. We report that disruption of the mixed-lineage protein
kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial
cells causes severe blockade of blood flow and failure to recover in the murine
femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK
pathway is required for the formation of native collateral arteries that can
restore circulation following arterial occlusion. Disruption of the MLK-JNK
pathway causes decreased Dll4/Notch signaling, excessive sprouting angiogenesis,
and defects in developmental vascular morphogenesis. Our analysis demonstrates
that the MLK-JNK signaling pathway is a key regulatory mechanism that protects
against ischemia in arterial occlusive disease.
PMID- 27504809
TI - Significant 99mTc-MDP but Unimpressive 18F-NaF Gastric Activity in a Patient With
Multiple Myeloma.
AB - A 69-year-old man with a history of low back pain for more than 4 months
underwent Tc-MDP bone scan to determine the cause of the symptoms. In addition to
the osseous lesions, significant activity in the stomach wall was noted. However,
a subsequent F-NaF PET/CT only revealed bone lesion without increased activity in
the stomach wall. The cause of the back pain was eventually confirmed due to
multiple myeloma.
PMID- 27504810
TI - Chiral-index resolved length mapping of carbon nanotubes in solution using
electric-field induced differential absorption spectroscopy.
AB - The length of single-walled carbon nanotubes (SWCNTs) is an important metric for
the integration of SWCNTs into devices and for the performance of SWCNT-based
electronic or optoelectronic applications. In this work we propose a rather
simple method based on electric-field induced differential absorption
spectroscopy to measure the chiral-index-resolved average length of SWCNTs in
dispersions. The method takes advantage of the electric-field induced length
dependent dipole moment of nanotubes and has been verified and calibrated by
atomic force microscopy. This method not only provides a low cost, in situ
approach for length measurements of SWCNTs in dispersion, but due to the
sensitivity of the method to the SWCNT chiral index, the chiral index dependent
average length of fractions obtained by chromatographic sorting can also be
derived. Also, the determination of the chiral-index resolved length distribution
seems to be possible using this method.
PMID- 27504811
TI - The Zombie Plot: A Simple Graphic Method for Visualizing the Efficacy of a
Diagnostic Test.
AB - OBJECTIVE: One of the most important jobs of a radiologist is to pick the most
appropriate imaging test for a particular clinical situation. Making a proper
selection sometimes requires statistical analysis. The objective of this article
is to introduce a simple graphic technique, an ROC plot that has been divided
into zones of mostly bad imaging efficacy (ZOMBIE, hereafter referred to as the
"zombie plot"), that transforms information about imaging efficacy from the
numeric domain into the visual domain. CONCLUSION: The numeric rationale for the
use of zombie plots is given, as are several examples of the clinical use of
these plots. Two online calculators are described that simplify the process of
producing a zombie plot.
PMID- 27504812
TI - The Natural History of Primary Sclerosing Cholangitis in Children: A Large Single
Center Longitudinal Cohort Study.
AB - OBJECTIVES: Data regarding pediatric primary sclerosing cholangitis (PSC) natural
history are limited. We describe a large pediatric PSC cohort with longitudinal
follow-up. METHODS: The present study records review of pediatric patients with
PSC diagnosed between 1984 and 2014. RESULTS: N = 120 (63% M) ages 1 to 21 years
(median 14 years) at diagnosis. 27% (31/113) had autoimmune sclerosing
cholangitis (ASC), 24% had exclusive small duct PSC, METAVIR stage was F3-F4 in
41%. Eighty-one percent of patients with PSC had inflammatory bowel disease
(IBD); most had ulcerative/indeterminate colitis (72/97), typically pancolitis
(40/72). PSC-IBD was more common than ASC-IBD (85% vs 68%, P = 0.03). Median
follow-up was 3.7 years (interquartile range [IQR] 1.5, 6.9). Median gamma
glutamyl transferase decreased from baseline of 221 U/L (IQR 110, 425) to 104 U/L
by 1 year postdiagnosis ([IQR 18,229], P < 0.0001), and then changed little. Mean
fibrosis stage at diagnosis was 2.3 +/- 1.4 (N = 91), and at 1 to 5 years was 2.6
+/- 1.3 (N = 20). Transplant-free survival at 10 year was 89%; there were 6 liver
transplants, 2 in patients with small duct PSC and 4 with diffuse large duct PSC.
Although the cirrhosis rate was not significantly different in PSC with IBD
versus without (22% vs 41%, P = 0.06), the former had a lower rate of liver
transplantation (2% vs 18%, P = 0.01). The rate of cirrhosis was lower in
patients diagnosed with IBD before PSC (15% vs 31%, P = 0.05). CONCLUSIONS: In
this largest reported pediatric PSC cohort, liver transplantation rate at 10
years was lower than that reported in adults. ASC and PSC had similar biochemical
abnormalities and degree of fibrosis at diagnosis. PSC that developed after IBD
diagnosis had a milder course, possibly reflecting earlier disease detection or
milder phenotype.
PMID- 27504813
TI - "Twin" Biliary Trees in a Patient With Heterotaxy Syndrome.
PMID- 27504814
TI - Predictive Value of Fecal Calprotectin in Pediatric Graft-Versus-Host Disease.
PMID- 27504815
TI - Adenomyomatosis of the Gallbladder with Pancreaticobiliary Maljunction in a
Child.
PMID- 27504817
TI - Technical adequacy of growth estimates from a computer adaptive test:
Implications for progress monitoring.
AB - Computer adaptive tests (CATs) hold promise to monitor student progress within
multitiered systems of support. However, the relationship between how long and
how often data are collected and the technical adequacy of growth estimates from
CATs has not been explored. Given CAT administration times, it is important to
identify optimal data collection schedules to minimize missed instructional time.
We used simulation methodology to investigate how the duration and frequency of
data collection influenced the reliability, validity, and precision of growth
estimates from a math CAT. A progress monitoring dataset of 746 Grade 4, 664
Grade 5, and 400 Grade 6 students from 40 schools in the upper Midwest was used
to generate model parameters. Across grades, 53% of students were female and 53%
were White. Grade level was not as influential as the duration and frequency of
data collection on the technical adequacy of growth estimates. Low-stakes
decisions were possible after 14-18 weeks when data were collected weekly (420
540 min of assessment), 20-24 weeks when collected every other week (300-360 min
of assessment), and 20-28 weeks (150-210 min of assessment) when data were
collected once a month, depending on student grade level. The validity and
precision of growth estimates improved when the duration and frequency of
progress monitoring increased. Given the amount of time required to obtain
technically adequate growth estimates in the present study, results highlight the
importance of weighing the potential costs of missed instructional time relative
to other types of assessments, such as curriculum-based measures. Implications
for practice, research, as well as future directions are also discussed.
(PsycINFO Database Record
PMID- 27504818
TI - Optical analysis of samarium doped sodium bismuth silicate glass.
AB - Samarium doped sodium bismuth silicate glass was synthesized using the melt
quenching method. Detailed optical spectroscopic studies of the glassy material
were carried out in the UV-Vis-NIR spectral range. Using the optical absorption
spectra Judd-Ofelt (JO) parameters are derived. The calculated values of the JO
parameters are utilized in evaluating the various radiative parameters such as
electric dipole line strengths (Sed), radiative transition probabilities (Arad),
radiative lifetimes (taurad), fluorescence branching ratios (beta) and the
integrated absorption cross- sections (sigmaa) for stimulated emission from
various excited states of Sm3+? ion. The principal fluorescence transitions are
identified by recording the fluorescence spectrum. Our analysis revealed that the
novel glassy system has the optimum values for the key parameters viz.
spectroscopic quality factor, optical gain, stimulated emission cross section and
quantum efficiency, which are required for a high performance optical amplifier.
Calculated chromaticity co-ordinates (0.61, 0.38) also confirm its application
potential in display devices.
PMID- 27504819
TI - Synthesis and improved photochromic properties of pyrazolones in the solid state
by incorporation of halogen.
AB - Four novel photochromic pyrazolones have been prepared by introducing halogen
atoms as substituents on the benzene ring. All as-synthesized compounds exhibited
excellent reversible photochromic performances in the solid state. Upon UV light
irradiation, the as-synthesized compounds can change their structures from E-form
to K-form with yellow coloration. Further processed by heating, they rapidly
reverted to their initial states at 120 degrees S. Their photo-response and
thermal bleaching kinetics were detailed investigated by UV absorption spectra.
The results showed that the time constants were higher than that of our
previously reported compounds at least one order of magnitude and the rate
constants of the as-synthesized compounds were significantly influenced by the
size and electronegativity of different halogen atoms. The fluorescence emission
were modulated in a high degree via photoisomerization of pyrazolones, which
might be due to the efficient energy transfer from E-form to K-form isomers for
their partly overlaps between their E-form absorption spectra and K-form
fluorescence spectra.
PMID- 27504820
TI - Effectiveness of the transpalatal arch in controlling orthodontic anchorage in
maxillary premolar extraction cases: A systematic review and meta-analysis.
AB - OBJECTIVE: To evaluate the effectiveness of the transpalatal arch (TPA) as an
anchorage device in preventing maxillary molar mesialization during retraction of
the anterior teeth after premolar extraction. MATERIALS AND METHODS: This
systematic review intended to include patients indicated for upper premolar
bilateral extraction and subsequent retraction of anterior teeth, considering the
use of TPA as an anchorage tool in one of the treatment groups. The search was
systematically performed, up to April 2015, in the following electronic
databases: Medline, Embase, and all evidence-based medicine reviews via OVID,
Cochrane Library, Scopus, PubMed, and Web of Science. Risk of bias assessment was
performed using Cochrane's Risk of Bias Tool for randomized clinical trials
(RCTs) and Methodological Index for Nonrandomized Studies (MINORS) for non-RCTs.
RESULTS: Fourteen articles were finally included. Nine RCTs and five non-RCTs
presented moderate to high risk of bias. Only one study investigated the use of
TPA in comparison with no anchorage, failing to show significant differences
regarding molar anchorage loss. A meta-analysis showed a significant increase in
anchorage control when temporary anchorage devices were compared with TPA (mean
difference [MD] 2.09 [95% confidence interval {CI} 1.80 to 2.38], seven trials),
TPA + headgear (MD 1.71 [95% CI 0.81 to 2.6], four trials), and TPA + utility
arch (MD 0.63 [95% CI 0.12 to 1.15], 3 trials). CONCLUSION: Based on mostly
moderate risk of bias and with some certainty level, TPA alone should not be
recommended to provide maximum anchorage during retraction of anterior teeth in
extraction cases.
PMID- 27504821
TI - Orthodontically induced external apical root resorption in patients treated with
fixed appliances vs removable aligners.
AB - OBJECTIVE: To determine whether orthodontic treatment with removable aligners vs
fixed orthodontic appliances is associated with a different frequency of
orthodontically induced external apical root resorption (OIEARR) when genetic,
radiographic, and clinical factors are accounted for. MATERIALS AND METHODS:
Three hundred seventy-two orthodontic patients treated with removable aligners
(Invisalign) or fixed appliances were genetically screened for interleukin 1B
gene (IL1B) (rs1143634), interleukin 1 receptor antagonist gene (IL1RN)
(rs419598), and osteopontin gene (SPP1) (rs9138/rs11730582). Twelve clinical
variables, potentially associated with OIEARR, were also considered. Subjects
were divided according to the presence of radiographically determined OIEARR (>2
mm). The association between OIEARR and appliance type, and radiographic,
clinical and genetic factors, was assessed using backward stepwise conditional
logistic regression. Odds ratios (ORs) and 95% confidence intervals (CIs) were
reported. RESULTS: Reliability of the methods was adequate. Clinical case
complexity (American Board of Orthodontics [ABO] Discrepancy Index) (OR: 1.032;
95% CI: 1.005-1.061; P = .021) and extent of incisor apical displacement in the
sagittal plane (OR: 1.478; 95% CI: 1.285-1.699; P = .001) were associated with an
increased OIEARR risk. After adjusting for associations between
clinical/radiographic/genetic factors, there were no statistically significant
differences with respect to OIEARR or type of orthodontic appliance used, whether
removable aligners or fixed appliances (OR: 1.662; 95% CI: 0.945-2.924; P =
.078). Only subjects homozygous for the T allele of IL1RN (rs419598) were more
prone to OIEARR during orthodontic treatment (OR: 3.121; CI: 1.93-5.03; P <
.001). CONCLUSIONS: A similar OIEARR predisposition was identified using either
removable aligners (Invisalign) or fixed appliances.
PMID- 27504822
TI - The Role of p-STAT3 as a Prognostic and Clinicopathological Marker in Colorectal
Cancer: A Systematic Review and Meta-Analysis.
AB - OBJECTIVE: High expression of phosphorylated signal transducer and activator of
transcription 3 (p-STAT3) has been detected in a variety of human tumors.
However, the association of positive p-STAT3 expression with clinicopathological
parameters and the prognosis of colorectal cancer patients remain controversial.
To identify the relationship between p-STAT3 expression and clinicopathological
parameters and prognosis in patients with colorectal cancer, a systematic review
and meta-analysis were performed. METHODS: We performed a comprehensive
literature search from PubMed, EMBASE, and SinoMed through 27 March, 2016. Hazard
ratios (HRs) with 95% confidence intervals (CI) were combined to evaluate the
association between p-STAT3 expression and overall survival of colorectal cancer
patients. Odds ratios (ORs) with 95% CI were combined to evaluate the association
between p-STAT3 expression and clinicopathological parameters in patients with
colorectal cancer. RESULTS: Seventeen studies including a total of 2,346
colorectal cancer patients were included in this meta-analysis. The combined HR
was 1.43 (95% CI: 1.23-1.67, P < 0.001), which suggested a positive relationship
between p-STAT3 overexpression and poorer overall survival of colorectal cancer
patients. In addition, the results indicated that positive p-STAT3 expression was
significantly associated with the presence of lymph node metastasis (OR: 2.43,
95% CI: 1.18-5.01, P = 0.02) but was not associated with TNM stage, tumor
differentiation or gender. CONCLUSION: The meta-analysis results suggest that p
STAT3 overexpression is unfavorable for the prognosis of colorectal cancer
patients, and p-STAT3 overexpression is associated with the presence of lymph
node metastasis among colorectal cancer patients.
PMID- 27504823
TI - Cluster Sampling Bias in Government-Sponsored Evaluations: A Correlational Study
of Employment and Welfare Pilots in England.
AB - For pilot or experimental employment programme results to apply beyond their test
bed, researchers must select 'clusters' (i.e. the job centres delivering the new
intervention) that are reasonably representative of the whole territory. More
specifically, this requirement must account for conditions that could
artificially inflate the effect of a programme, such as the fluidity of the local
labour market or the performance of the local job centre. Failure to achieve
representativeness results in Cluster Sampling Bias (CSB). This paper makes three
contributions to the literature. Theoretically, it approaches the notion of CSB
as a human behaviour. It offers a comprehensive theory, whereby researchers with
limited resources and conflicting priorities tend to oversample 'effect
enhancing' clusters when piloting a new intervention. Methodologically, it
advocates for a 'narrow and deep' scope, as opposed to the 'wide and shallow'
scope, which has prevailed so far. The PILOT-2 dataset was developed to test this
idea. Empirically, it provides evidence on the prevalence of CSB. In conditions
similar to the PILOT-2 case study, investigators (1) do not sample clusters with
a view to maximise generalisability; (2) do not oversample 'effect-enhancing'
clusters; (3) consistently oversample some clusters, including those with higher
than-average client caseloads; and (4) report their sampling decisions in an
inconsistent and generally poor manner. In conclusion, although CSB is prevalent,
it is still unclear whether it is intentional and meant to mislead stakeholders
about the expected effect of the intervention or due to higher-level constraints
or other considerations.
PMID- 27504824
TI - Spontaneous Alpha Power Lateralization Predicts Detection Performance in an Un
Cued Signal Detection Task.
AB - Focusing one's attention by external guiding stimuli towards a specific area of
the visual field produces systematical neural signatures. One of the most robust
is the change in topological distribution of oscillatory alpha band activity
across parieto-occipital cortices. In particular, decreases in alpha activity
over contralateral and/or increases over ipsilateral scalp sites, respect to the
side of the visual field where attention was focused. This evidence comes mainly
from experiments where an explicit cue informs subjects where to focus their
attention, thus facilitating detection of an upcoming target stimulus. However,
recent theoretical models of attention have highlighted a stochastic or non
deterministic component related to visuospatial attentional allocation. In an
attempt to evidence this component, here we analyzed alpha activity in a signal
detection paradigm in the lack of informative cues; in the absence of preceding
information about the location (and time) of appearance of target stimuli. We
believe that the unpredictability of this situation could be beneficial for
unveiling this component. Interestingly, although total alpha power did not
differ between Seen and Unseen conditions, we found a significant lateralization
of alpha activity over parieto-occipital electrodes, which predicted behavioral
performance. This effect had a smaller magnitude compared to paradigms in which
attention is externally guided (cued). However we believe that further
characterization of this spontaneous component of attention is of great
importance in the study of visuospatial attentional dynamics. These results
support the presence of a spontaneous component of visuospatial attentional
allocation and they advance pre-stimulus alpha-band lateralization as one of its
neural signatures.
PMID- 27504825
TI - Global Electricity Trade Network: Structures and Implications.
AB - Nations increasingly trade electricity, and understanding the structure of the
global power grid can help identify nations that are critical for its
reliability. This study examines the global grid as a network with nations as
nodes and international electricity trade as links. We analyze the structure of
the global electricity trade network and find that the network consists of four
sub-networks, and provide a detailed analysis of the largest network, Eurasia.
Russia, China, Ukraine, and Azerbaijan have high betweenness measures in the
Eurasian sub-network, indicating the degrees of centrality of the positions they
hold. The analysis reveals that the Eurasian sub-network consists of seven
communities based on the network structure. We find that the communities do not
fully align with geographical proximity, and that the present international
electricity trade in the Eurasian sub-network causes an approximately 11 million
additional tons of CO2 emissions.
PMID- 27504826
TI - Towards a Collaborative Research: A Case Study on Linking Science to Farmers'
Perceptions and Knowledge on Arabica Coffee Pests and Diseases and Its
Management.
AB - The scientific community has recognized the importance of integrating farmer's
perceptions and knowledge (FPK) for the development of sustainable pest and
disease management strategies. However, the knowledge gap between indigenous and
scientific knowledge still contributes to misidentification of plant health
constraints and poor adoption of management solutions. This is particularly the
case in the context of smallholder farming in developing countries. In this
paper, we present a case study on coffee production in Uganda, a sector depending
mostly on smallholder farming facing a simultaneous and increasing number of
socio-ecological pressures. The objectives of this study were (i) to examine and
relate FPK on Arabica Coffee Pests and Diseases (CPaD) to altitude and the
vegetation structure of the production systems; (ii) to contrast results with
perceptions from experts and (iii) to compare results with field observations, in
order to identify constraints for improving the information flow between
scientists and farmers. Data were acquired by means of interviews and workshops.
One hundred and fifty farmer households managing coffee either at sun exposure,
under shade trees or inter-cropped with bananas and spread across an altitudinal
gradient were selected. Field sampling of the two most important CPaD was
conducted on a subset of 34 plots. The study revealed the following findings: (i)
Perceptions on CPaD with respect to their distribution across altitudes and
perceived impact are partially concordant among farmers, experts and field
observations (ii) There are discrepancies among farmers and experts regarding
management practices and the development of CPaD issues of the previous years.
(iii) Field observations comparing CPaD in different altitudes and production
systems indicate ambiguity of the role of shade trees. According to the locality
specific variability in CPaD pressure as well as in FPK, the importance of
developing spatially variable and relevant CPaD control practices is proposed.
PMID- 27504827
TI - Health-Related Quality of Life (HRQoL) in Idiopathic Inflammatory Myopathy: A
Systematic Review.
AB - Health-related quality of life (HRQoL) is a research priority in chronic
diseases. We undertook a systematic review (registration #CRD42015024939) to
identify, appraise and synthesize the evidence relating to HRQoL in idiopathic
inflammatory myopathies (IIM). A comprehensive search was conducted in August
2015 using CINAHL, EMBase and Pubmed to identify studies reporting original data
on HRQoL in IIM using generic HRQoL instruments. Characteristics of samples and
results from selected studies were extracted and appraised using a standardized
approach. Qualitative synthesis of the results was performed. Ten studies
including a total of 654 IIM subjects were included in this systematic review.
HRQoL was significantly impaired in all subsets of IIM compared with the general
population. Disease activity, disease damage and chronic disease course were
associated with poorer HRQoL. Insufficient or conflicting results were found in
associations between clinical features, treatment, disease duration and mood or
illness perception, and HRQoL in IIM. This study suggests that HRQoL is impaired
in IIM. However, due to the paucity and heterogeneity of the evidence to date,
robust estimates are lacking and significant knowledge gaps persist. There is a
need for studies that systematically investigate the correlates and trajectory of
HRQoL in IIM.
PMID- 27504828
TI - Asymptomatic Vivax and Falciparum Parasitaemia with Helminth Co-Infection: Major
Risk Factors for Anaemia in Early Life.
AB - BACKGROUND: Anaemia in children under five years old is associated with poor
health, growth and developmental outcomes. In Papua, Indonesia, where the burden
of anaemia in infants is high, we conducted a community survey to assess the
association between Plasmodium infection, helminth carriage and the risk of
anaemia. METHODS: A cross sectional household survey was carried out between
April and July 2013 in 16 villages in the District of Mimika using a multistage
sampling procedure. A total of 629 children aged 1-59 months from 800 households
were included in the study. Demographic, symptom and anthropometry data were
recorded using a standardized questionnaire. Blood and stool samples were
collected for examination. RESULTS: Of the 533 children with blood film
examination, 8.8% (47) had P. vivax parasitaemia and 3.9% (21) had P. falciparum;
the majority of children with malaria were asymptomatic (94.4%, 68/72). Soil
transmitted helminth (STH) infection was present in 43% (105/269) of children
assessed; those with STH were at significantly greater risk of P. vivax
parasitaemia compared to those without STH (OR = 3.7 [95%CI 1.5-9.2], p = 0.004).
Anaemia (Hb<10 g/dl) was present in 24.5% (122/497) of children and associated
with P. vivax parasitaemia (OR = 2.9 [95%CI, 1.7-4.9], p = 0.001), P. falciparum
parasitaemia (OR = 4.3 [95%CI, 2.0-9.4], p<0.001), hookworm carriage (OR = 2.6
[95%CI, 1.2-5.8], p = 0.026), Plasmodium-helminth coinfection (OR 4.0 [95%CI, 1.4
11.3], p = 0.008) and severe stunting (OR = 1.9 ([95%CI, 1.1-3.3], p = 0.012).
CONCLUSIONS: Asymptomatic P. vivax and P. falciparum infections and hookworm all
contribute to risk of paediatric anaemia in coendemic areas and should be
targeted with prevention and treatment programs. The relationship between
helminth infections and the increased risk of P. vivax parasitaemia should be
explored prospectively.
PMID- 27504829
TI - Linking Core Promoter Classes to Circadian Transcription.
AB - Circadian rhythms in transcription are generated by rhythmic abundances and DNA
binding activities of transcription factors. Propagation of rhythms to
transcriptional initiation involves the core promoter, its chromatin state, and
the basal transcription machinery. Here, I characterize core promoters and
chromatin states of genes transcribed in a circadian manner in mouse liver and in
Drosophila. It is shown that the core promoter is a critical determinant of
circadian mRNA expression in both species. A distinct core promoter class, strong
circadian promoters (SCPs), is identified in mouse liver but not Drosophila. SCPs
are defined by specific core promoter features, and are shown to drive circadian
transcriptional activities with both high averages and high amplitudes. Data
analysis and mathematical modeling further provided evidence for rhythmic
regulation of both polymerase II recruitment and pause release at SCPs. The
analysis provides a comprehensive and systematic view of core promoters and their
link to circadian mRNA expression in mouse and Drosophila, and thus reveals a
crucial role for the core promoter in regulated, dynamic transcription.
PMID- 27504830
TI - A Family History of Stroke Is Associated with Increased Intima-Media Thickness in
Young Ischemic Stroke - The Norwegian Stroke in the Young Study (NOR-SYS).
AB - BACKGROUND AND PURPOSE: Positive family history (FH+) of cardiovascular disease
(CVD) is a risk factor for own CVD. We aimed to analyze the effect of different
types of FH (stroke, coronary heart disease (CHD), peripheral artery disease
(PAD) on carotid intima-media thickness (cIMT) in young and middle-aged ischemic
stroke patients. METHODS: First-degree FH of CVD was assessed in ischemic stroke
patients <= 60y using a standardized interview. Carotid ultrasound was performed
and far wall cIMT in three carotid artery segments was registered, representing
the common carotid (CCA-IMT), carotid bifurcation (BIF-IMT) and the internal
carotid artery (ICA-IMT). Measurements were compared between FH+ and FH negative
groups and stepwise backward regression analyses were performed to identify
factors associated with increased cIMT. RESULTS: During the study period 382
patients were enrolled, of which 262 (68%) were males and 233 (61%) reported FH
of CVD. Regression analyses adjusting for risk factors revealed age as the most
important predictor of cIMT in all segments. The association between FH+ and cIMT
was modified by age (p = 0.014) and was significant only regarding ICA-IMT. FH+
was associated with increased ICA-IMT in patients aged < 45y (p = 0.001), but not
in patients >= 45y (p = 0.083). The association with ICA-IMT was present for a FH
of stroke (p = 0.034), but not a FH+ of CHD or PAD. CONCLUSIONS: FH of stroke is
associated with higher ICA-IMT in young ischemic stroke patients. Subtyping of
cardiovascular FH is important to investigate heredity in young ischemic stroke
patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01597453.
PMID- 27504831
TI - Correction: Guidelines for Accurate and Transparent Health Estimates Reporting:
the GATHER statement.
AB - [This corrects the article DOI: 10.1371/journal.pmed.1002056.].
PMID- 27504832
TI - Biological Maturity Status Strongly Intensifies the Relative Age Effect in Alpine
Ski Racing.
AB - The relative age effect (RAE) is a well-documented phenomenon in youth sports.
This effect exists when the relative age quarter distribution of selected
athletes shows a biased distribution with an over-representation of relatively
older athletes. In alpine ski racing, it exists in all age categories (national
youth levels up to World Cup). Studies so far could demonstrate that selected ski
racers are relatively older, taller and heavier. It could be hypothesized that
relatively younger athletes nearly only have a chance for selection if they are
early maturing. However, surprisingly this influence of the biological maturity
status on the RAE could not be proven, yet. Therefore, the aim of the present
study was to investigate the influence of the biological maturity status on the
RAE in dependence of the level of competition. The study investigated 372 elite
youth ski racers: 234 provincial ski racers (P-SR; high level of competition) and
137 national ski racers (N-SR; very high level of competition). Anthropometric
characteristics were measured to calculate the age at peak height velocity (APHV)
as an indicator of the biological maturity status. A significant RAE was present
among both P-SR and N-SR, with a larger effect size among the latter group. The N
SR significantly differed in APHV from the P-SR. The distribution of normal,
early and late maturing athletes significantly differed from the expected normal
distribution among the N-SR, not among the P-SR. Hardly any late maturing N-SR
were present; 41.7% of the male and 34% of the female N-SR of the last relative
age quarter were early maturing. These findings clearly demonstrate the
significant influence of the biological maturity status on the selection process
of youth alpine ski racing in dependence of the level of competition. Relatively
younger athletes seem to have a chance of selection only if they are early
maturing.
PMID- 27504833
TI - Elements of Effective Interventions for Addressing Intimate Partner Violence in
Latina Women: A Systematic Review.
AB - BACKGROUND: Intimate partner violence remains a global problem and is of
particular concern in Latina diasporas. AIM: To identify effective elements of
interventions to address intimate partner violence in Latina women. METHOD: The
systematic review was undertaken according to Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We focused the search
on intervention studies assessing intimate partner violence as an outcome measure
and on publications in English and Spanish from the last 11 years (2004-2015).
RESULTS: Despite the scope of the problem, from the 1,274 studies screened only
four met the search criteria and only a single study included an exclusive Latino
population. Of the four interventions, one was only as effective as the control
treatment. Heterogeneity of study populations and designs prohibited meta
analytic methods. CONCLUSIONS: Theoretically derived interventions that are
gender specific, culturally appropriate, target mutual aid through group
dynamics, and that are developed collaboratively with the target population are
likely to be most effective.
PMID- 27504834
TI - [Calf health and antimicrobial use in Swiss dairy herds: Management, prevalence
and treatment of calf diseases].
AB - INTRODUCTION: Fifty-two dairy herds in the canton Fribourg were included during
one winter in a study on calf management, prevalence and treatments of calf
diseases. Colostrum management was optimal in 46.2% of the herds only, and 51.3%
of the calves had been sick at least once during the observation period. The most
commonly observed diseases included respiratory disease (57.5%), diarrhea (32.8%)
and umbilical disease (5.7%). Cases of pneumonia were treated with antimicrobials
first by the farmers in 65.4% of the herds. Calf diarrhea was treated with
antimicrobial drugs by 57.7% of the farmers. Fluorochinolones were used in 47% of
all parenteral treatments and oral antimicrobial drugs included macrolides in 11%
of the cases. These results provide information on calf management, calf health
and treatment strategies in an area where dairying is the most important sector
of the farming industry. They show clearly that the farmers are not sufficiently
informed about the use of critically important antimicrobial drugs and about the
etiology of calf diarrhea. Improvements in colostrum management and treatment
strategies are urgently needed.
PMID- 27504835
TI - [Bacterial resistance in bacteria isolated from the nasal cavity of Swiss dairy
calves].
AB - INTRODUCTION: Fifty-six E. coli, 37 P. multocida und 8 M. haemolytica were
isolated from 157 nasal swabs taken from calves in 52 dairy herds. The antibiotic
susceptibility of the organisms was determined by measurement of the minimal
inhibitory concentrations. Of the 56 E. coli isolates, 55.3% exhibited resistance
to tetracyclines, 55.3% to sulfonamides, 39.3% to beta-lactams, 30.3% to
aminoglycosides, 8.9% to fluorochinolones and 3.5% to 3rd generation
cephalosporins. The 3rd generation cephalosporin- resistant isolates contained
the extended spectrum-beta-lactamase gene blaCTX-M-14 and came from 2 farms where
the milk of cows under antimicrobial treatment was fed to the calves and mastitis
was treated with cefquinome as first line therapy. Of the 37 P. multocida
isolates, 48.6% exhibited resistance to tetracyclines, 16.2% to beta-lactams, and
5.4% each to macrolides, aminoglycosides and sulfonamides. The 8 M. haemolytica
isolates showed no resistances against the tested antibiotics.
PMID- 27504836
TI - Antimicrobial susceptibility of Brachyspira hyodysenteriae in Switzerland.
AB - INTRODUCTION: Brachyspira (B.) hyodysenteriae is the causative agent of swine
dysentery (SD), a severe mucohaemorrhagic diarrheal disease in pigs worldwide. So
far, the antimicrobial susceptibility patterns of B. hyodysenteriae in
Switzerland have not been investigated. Therefore, a panel of 30 porcine B.
hyodysenteriae isolates were tested against 6 antimicrobial agents by using the
VetMIC Brachy panel, a broth microdilution test. Tiamulin and valnemulin showed
high antimicrobial activity inhibiting all isolates at low concentrations. The
susceptibility testing of doxycycline revealed values from <=0.25 MUg/ ml (47%)
to 2 MUg/ml (10%). The MIC values of lincomycin ranged between <=0.5 MUg/ml (30%)
and 32 MUg/ml (43%). For tylosin, 57% of the isolates could not be inhibited at
the highest concentration of >=128 MUg/ml. The MIC values for tylvalosin were
between <=0.25 MUg/ml (10%) and 8 MUg/ml (20%). These findings reveal
Switzerland's favourable situation compared to other European countries. Above
all, tiamulin and valnemulin are still effective antimicrobial agents and can be
further used for the treatment of SD.
PMID- 27504837
TI - The effect of the administration of three different antimicrobial premix
formulations via the liquid feeding system on the occurrence of
Enterobacteriaceae resistant to tetracycline in the liquid feed for pigs.
AB - INTRODUCTION: The oral group treatment is still a common procedure in swine
production. This project studied the effect of the application of 3 different
formulations of antimicrobial premixes (1. chlortetracycline, 2.
chlortetracycline + sulfadimidine + tylosin, 3. sulfadimidine + sulfathiazole +
trimethoprim) via the liquid feeding system on the occurrence of tetracycline
resistant Enterobacteriaceae (Ent-Tetr) in the liquid feed. 156 and 112 feed
samples were collected between April and December 2015 in 13 case and 14 control
farms, respectively. The 27 farms were randomly selected pig fattening farms
located in different parts of Switzerland. The number of feed samples that
contained Ent-Tetr as well as the number of Enterobacteriaceae resistant to
tetracycline per sample was significantly higher in the case group than in the
control group. The use of any of the 3 antimicrobial combinations turned out to
be the main risk factor for the occurrence of Ent-Tetr in the liquid feed. Our
results suggest that liquid feed containing antimicrobials is a reservoir of
antimicrobial resistant bacteria in swine production.
PMID- 27504838
TI - A retrospective analysis of antimicrobial resistance in bacterial pathogens in an
equine hospital (2012-2015).
AB - INTRODUCTION: Antimicrobial resistance has become an important concern in
veterinary medicine. The aim of this study was to describe the rate of
antimicrobial resistance in common equine pathogens and to determine the
occurrence of multidrug-resistant isolates. A retrospective analysis of all
susceptibility testing results from bacterial pathogens cultured from horses at
the University of Zurich Equine Hospital (2012-2015) was performed. Strains
exhibiting resistance to 3 or more antimicrobial categories were defined as
multidrug-resistant. Susceptibility results from 303 bacterial pathogens were
analyzed, most commonly Escherichia coli (60/303, 20%) and Staphylococcus aureus
(40/303, 13%). High rates of acquired resistance against commonly used
antimicrobials were found in most of the frequently isolated equine pathogens.
The highest rate of multidrug resistance was found in isolates of Acinetobacter
baumannii (23/24, 96%), followed by Enterobacter cloacae complex (24/28, 86%) and
Escherichia coli (48/60, 80%). Overall, 60% of Escherichia coli isolates were
phenotypically ESBL-producing and 68% of Staphylococcus spp. were phenotypically
methicillin-resistant. High rates of acquired antimicrobial resistance towards
commonly used antibiotics are concerning and underline the importance of
individual bacteriological and antimicrobial susceptibility testing to guide
antimicrobial therapy. Minimizing and optimizing antimicrobial therapy in horses
is needed.
PMID- 27504839
TI - Methicillin-resistant Staphylococcus aureus isolated from dogs and cats in
Switzerland.
AB - INTRODUCTION: Twenty-two methicillin-resistant Staphylococcus aureus (MRSA)
strains isolated from various infected locations in domestic cats and dogs
between June 2008 and September 2014 were analyzed for their genotype, genetic
fingerprint, virulence and antibiotic resistance profile. Eighteen strains
belonged to the clonal complex (CC) 22 [ST22(MLST)-A(PFGE)-t032(spa)-IV(SCCmec)
and ST22-A-t1214-IV], 2 strains to the livestock associated MRSA ST398-t011-IV
and two were individual strains of ST5-t002-II and ST1-t001-IV. They contained
virulence factors such as gamma-hemolysins, beta-hemolysin converting phage
genes, leukocidins and enterotoxins. Most widespread resistances were observed
against beta-lactams, trimethoprim and fluoroquinolones, but single strains also
exhibited resistance to macrolides, lincosamides, aminoglycosides, tetracycline,
chloramphenicol and/or mupirocin. The predominant presence of CC22 MRSA strongly
indicates clonal spread of a human associated lineage in Swiss companion animals.
It is therefore of public health importance to maintain a low level of MRSA
infections in animals to avoid uncontrolled dissemination of MRSA clones in
humans and animals.
PMID- 27504840
TI - Characteristics of ESBL-producing Enterobacteriaceae and Methicillinresistant
Staphylococcus aureus (MRSA) isolated from Swiss and imported raw poultry meat
collected at retail level.
AB - INTRODUCTION: This study was conducted to investigate the occurrence and genetic
characteristics of extended spectrum beta-lactamase (ESBL) and methicillin
resistant Staphylococcus aureus (MRSA) in 80 samples of Swiss (n=36) and imported
(n=44) raw chicken meat collected at retail level. In addition, ESBL-producers
were screened for the presence of the plasmid-mediated colistin resistance gene
mcr-1. Countries of import included Argentina (n=2), Austria (n=1), Brazil (n=3),
Denmark (n=5), France (n=1), Germany (n=13), Hungary (n=5), Italy (n=8), and
Slovenia (n=6). Forty ESBL-producing E. coli strains were isolated from 33
(41.3%) of the 80 samples, comprising seven (19.4%) of the Swiss and 26 (59%) of
the imported samples. The most common blaESBL among the isolates were blaCTX-M-1
(n=14) and blaSHV-12 (n=16). Other genes comprised blaTEM-52 (n=4), blaCTX-M-2
(n=3), blaCTX-M-8 (n=1), blaCTX-M-14 (n=1) and a novel blaCTX-M-14-like variant
(n=1). Two ESBL-producers isolated from samples from Germany (n=1) and Italy
(n=1) tested additionally positive for the plasmid-mediated colistin resistance
gene mcr-1. Six (7.5%) samples, all imported from Germany, were found to contain
MRSA. Three isolates belonged to the livestock-associated CC398-MRSA-V-t034, and
3 to CC9-MRSA-IV-t13177, described here for the first time in chicken meat.
PMID- 27504841
TI - Occurrence and features of chromosomally encoded carbapenemases in Gram-negative
bacteria in farm animals sampled at slaughterhouse level.
PMID- 27504842
TI - Review of the Tuberous Sclerosis Renal Guidelines from the 2012 Consensus
Conference: Current Data and Future Study.
AB - Renal-related disease is the most common cause of tuberous sclerosis complex
(TSC)-related death in adults, and renal angiomyolipomas can lead to
complications that include chronic kidney disease (CKD) and hemorrhage.
International TSC guidelines recommend mammalian target of rapamycin (mTOR)
inhibitors as first-line therapy for management of asymptomatic, growing
angiomyolipomas >3 cm in diameter. This review discusses data regarding patient
outcomes that were used to develop current guidelines for embolization of renal
angiomyolipomas and presents recent data on 2 available mTOR inhibitors -
sirolimus and everolimus - in the treatment of angiomyolipoma. TSC-associated
renal angiomyolipomas can recur after embolization. Both sirolimus and everolimus
have shown effectiveness in reduction of angiomyolipoma volume, with an
acceptable safety profile that includes preservation of renal function with long
term therapy. The authors propose a hypothesis for mTORC1 haploinsufficiency as
an additional mechanism for CKD and propose that preventive therapy with mTOR
inhibitors might have a role in reducing the number of angiomyolipoma-related
deaths. Because mTOR inhibitors target the underlying pathophysiology of TSC,
patients might benefit from treatment of multiple manifestations with one
systemic therapy. Based on recent evidence, new guidelines should be considered
that support the earlier initiation of mTOR inhibitor therapy for the management
of renal angiomyolipomas to prevent future serious complications, rather than try
to rescue patients after the complications have occurred.
PMID- 27504843
TI - Aortic Stiffness and Inflammation: Dyslipidemia or Matrix Metalloproteinases?
PMID- 27504844
TI - Rethinking happiness: using your power for purposea.
PMID- 27504845
TI - Comparison of Oral Health Education and Fluoride Varnish to Prevent Early
Childhood Caries: A Randomized Clinical Trial.
AB - Early childhood caries, a serious health problem among young children, can be
prevented with effective intervention. The aim of this study was to evaluate the
efficacy of oral health education and a fluoride varnish in the prevention of
caries in children under the age of 3 years. For this single-blind randomized
parallel group 1-year clinical trial in Shiraz, 300 children aged 12-24 months
with sound primary teeth were selected and randomly divided into three groups (n
= 100): (1) control: no preventive intervention; (2) oral health counseling, and
(3) oral health counseling and fluoride varnish at baseline and 6 months later.
At baseline and 4, 8 and 12 months after the intervention, caries risk reduction
was recorded as the primary outcome. The mothers' knowledge and performance
regarding oral health in children was used as a secondary outcome. A total of 260
children (mean age: 20.49 +/- 7.33 months) completed the study. Compared to group
1, caries risk reduction in group 2 was 28% (95% CI: -39.05 to -17.45) and 31% in
group 3 (95% CI: -41.88 to -21.73). However, there was no significant difference
between groups 2 and 3 (95% CI: -8.58 to 1.47). In all groups, mothers' knowledge
and performance at baseline were low; however, they increased significantly in
follow-up appointments in groups 2 and 3 (p < 0.001). Oral health education
increased mothers' knowledge and performance regarding oral health in children.
Oral health counseling alone or associated with the use of fluoride varnish
reduced the caries incidence in young children.
PMID- 27504846
TI - A Catalytic Nanoreactor Based on in Vivo Encapsulation of Multiple Enzymes in an
Engineered Protein Nanocompartment.
AB - Bacterial protein compartments concentrate and sequester enzymes, thereby
regulating biochemical reactions. Here, we generated a new functional
nanocompartment in Escherichia coli by engineering the MS2 phage capsid protein
to encapsulate multiple cargo proteins. Sequestration of multiple proteins in MS2
based capsids was achieved by SpyTag/SpyCatcher protein fusions that covalently
crosslinked with the interior surface of the capsid. Further, the functional two
enzyme indigo biosynthetic pathway could be targeted to the engineered capsids,
leading to a 60 % increase in indigo production in vivo. The enzyme-loaded
particles could be purified in their active form and showed enhanced long-term
stability in vitro (about 95 % activity after seven days) compared with free
enzymes (about 5 % activity after seven days). In summary, this engineered in
vivo encapsulation system provides a simple and versatile way for generating
highly stable multi-enzyme nanoreactors for in vivo and in vitro applications.
PMID- 27504847
TI - Response to: Surgical trainee research collaboratives in the UK: An observational
study of research activity and publication productivity.
PMID- 27504848
TI - Laparoscopic versus open repair for perforated peptic ulcer: A meta analysis of
randomized controlled trials.
AB - INTRODUCTION: The role of laparoscopic surgery in the repair for peptic ulcer
disease is unclear. The present study aimed to compare the safety and efficacy of
laparoscopic versus open repair for peptic ulcer disease. METHODS: Randomized
controlled trials (RCTs) comparing laparoscopic versus open repair for peptic
ulcer disease were identified from MEDLINE, EMBASE, Cochrane Central Register of
Controlled Trials, and references of identified articles and relevant reviews.
Primary outcomes were postoperative complications, mortality, and reoperation.
Secondary outcomes were operative time, postoperative pain, postoperative
hospital stay, nasogastric tube duration, and time to resume diet. Statistical
analysis was carried out by Review Manage software. RESULTS: Five RCTs
investigating a total of 549 patients, of whom, 279 received laparoscopic repair
and 270 received open repair, were included in the final analysis. There were no
significant differences between these two procedures in some primary outcomes
including overal postoperative complication rate, mortality, and reoperation
rate. Subcategory analysis of postoperative complications showed that
laparoscopic repair had also similar rates of repair site leakage, intra
abdominal abscess, postoperative ileus, pneumonia, and urinary tract infection as
open surgery, except of the lower surgical site infection rate (P < 0.05). In
addition, there were also no significant differences between these two procedures
in some second outcomes including operative time, postoperative hospital stay,
and time to resume diet, but laparoscopic repair had shorter nasogastric tube
duration (P < 0.05) and less postoperative pain (P < 0.05) than open surgery.
CONCLUSIONS: Laparoscopic surgery is comparable with open surgery in the setting
of repair for perforated peptic ulcer. The obvious advantages of laparoscopic
surgery are the lower surgical site infection rate, shorter nasogastric tube
duration and less postoperative pain. However, more higher quality studies should
be undertaken to further assess the safety and efficacy of laparoscopic repair
for peptic ulcer disease.
PMID- 27504849
TI - Limited effectiveness of patent blue dye in addition to isotope scanning for
identification of sentinel lymph nodes: Cross-sectional real-life study in 1024
breast cancer patients.
AB - BACKGROUND: Although morbidity is reduced when sentinel lymph node (SLN) biopsy
is performed with dual isotopic and blue dye identification, the effectiveness of
adding blue dye to radioisotope remains debated because side effects including
anaphylactic reactions. PATIENTS AND METHODS: Using data from a prospectively
maintained database, 1884 lymph node-negative breast cancer patients who
underwent partial mastectomy with SLN mapping by a dual-tracer using patent blue
dye (PBD) and radioisotope were retrospectively studied between January 2000 and
July 2013. Patients with tumors <3 cm and with >1 node detected by one of the two
techniques (N = 1024) were included in this real-life cross-sectional study.
RESULTS: Among the 1024 patients, 274 had positive SLN detected by isotopic
and/or PBD staining. Only 4 patients having no detectable radioactivity in the
axilla had SLN identified only by PBD staining (blue-only) while 26 patients had
SLN only identified by isotopic detection (hot-only) illustrating failure rates
of 9.5% (26/274) and 1.5% (4/274), respectively. Among these four patients, two
had negative lymphoscintigraphy. Therefore, the contribution of PBD to metastatic
nodes identification was relevant for only 2/274 patients (0.8%). Three patients
(0.3%) had an allergic reaction with PBD, and anaphylactic shock occurred in two
cases (0.2%). CONCLUSIONS: The added-value of PBD to reduce the false-negative
rate of SLN mapping is only limited to the rare cases in which no radioactivity
is detectable in the axilla (<1%). When a radioisotope mapping agent is
available, the use of PBD should be avoided, because it can induce anaphylaxis.
PMID- 27504850
TI - Retinol-Binding Protein 4 Induces Hepatic Mitochondrial Dysfunction and Promotes
Hepatic Steatosis.
AB - CONTEXT AND OBJECTIVE: Elevated serum retinol-binding protein 4 (RBP4) has been
implicated in insulin resistant and nonalcoholic fatty liver disease (NAFLD)
subjects; however, the molecular mechanism of RBP4 in NAFLD remains obscure.
DESIGN AND PARTICIPANTS: Hepatic RBP4 mRNA level and its association with lipid
accumulation were examined in NAFLD patients and mouse model. Furthermore, human
RBP4 overexpressing (RBP4-Tg) mice were metabolically phenotyped after either a
regular chow or high-fat diet. RESULTS: RBP4 mRNA was aberrantly elevated in
NAFLD models and positively associated with increased hepatic triglyceride
accumulation. Compared with their wild-type littermates, RBP4-Tg mice fed regular
chow had increased hepatic lipid accumulation associated with cellular ballooning
and inflammatory changes, which was exacerbated when challenged with high-fat
diet. The acceleration of NAFLD in RBP4-Tg mice was mainly attributed to reduced
mitochondrial content and impaired mitochondrial fatty acid beta-oxidation. RBP4
overexpression promoted the acetylation of long-chain acyl-coenzyme A
dehydrogenase through inhibiting the expression and activity of NAD-dependent
deacetylase sirtuin-3 and significantly hampered the binding of long-chain acyl
coenzyme A dehydrogenase and NAD-dependent deacetylase sirtuin-3. Moreover, RBP4
induced mitochondrial dysfunction preceded the deterioration of lipid metabolism.
CONCLUSIONS: These results have unraveled a novel role of RBP4 in hepatic
mitochondrial dysfunction and steatosis and suggest that RBP4 might be a
potential target for the early prevention of NAFLD.
PMID- 27504851
TI - Steroid Metabolomic Disease Signature of Nonsyndromic Childhood Obesity.
AB - CONTEXT: The profile of urinary steroids as measured by gas chromatography-mass
spectrometry defines a subject's "steroidal fingerprint." OBJECTIVE: Here, we
clustered steroidal fingerprints to characterize patients with nonsyndromic
childhood obesity by "steroid metabolomic signatures." HYPOTHESIS: Nonsyndromic
obesity is a symptom of different diseases and conditions, some of them will have
their own signature. DESIGN: A total of 31 steroid metabolites were quantified by
gas chromatography-mass spectrometry, and their excretion rates were z
transformed. Using MetaboAnalyst 3.0, we divided the subjects into 5 distinctive
groups by k-means clustering. Steroidal fingerprints and clinical/biochemical
data of patients in each cluster were analyzed. PATIENTS: A total of 87 obese
children (44 females), aged 8.5-17.9 years, were clinically characterized, and
their 24-hour urine was collected. RESULTS: Cluster 1 (n = 39, 21 females) had
normal steroid profile. Cluster 2 (n = 20, 11 females) showed mild, nonspecific
elevation of C19 and C21 steroids, females' resistance to polycystic ovary
morphology, and hirsutism. Cluster 3 (n = 7 female), with relative 21-hydroxylase
insufficiency, was characterized by partial or full polycystic ovary syndrome.
Cluster 4 (n = 4 males), showed markedly elevated C21 steroids and imbalance in
the 11beta-hydroxysteroid dehydrogenase system, higher insulin, increased
frequency of glucose/insulin index more than 0.3, gamma-glutamyl transpeptidase
activity, systolic blood pressure, and tendency to liver steatosis. Cluster 5 (n
= 17, 5 females) had elevated dehydroepiandrosterone and 17-OH-pregnenolone
metabolites, suggesting 3beta-hydroxysteroid dehydrogenase insufficiency but no
clinically unique phenotype. Z-score body mass index values were not
significantly different between the clusters. CONCLUSIONS: We defined a novel
concept of disease-specific steroid metabolomic signature based on urinary
steroidal gas chromatography-mass spectrometry. Clustering by software designed
for metabolic data analysis reclassified childhood obesity into 5 groups with
distinctive signatures; groups require further definition and may require cluster
specific therapeutic strategies.
PMID- 27504852
TI - Insulinoma Due to Multiple Pancreatic Microadenoma Localized by Multimodal
Imaging.
AB - CONTEXT: Insulinomas are usually due to a solitary tumor, but they can be
challenging to localize. CASE DESCRIPTION: A 66-year-old woman presented with a 1
year history of episodic neuroglycopenic hypoglycemia and was suspected of having
an insulinoma. On a supervised fast, she was found to be hypoglycemic at 39
mg/dL, with an insulin of 40 MUU/mL 26 hours into the fast and a proinsulin of 35
pmol/L. Contrast-enhanced computed tomography and magnetic resonance imaging did
not localize a pancreatic lesion. Intra-arterial calcium stimulation testing
showed a step-up of venous insulin levels at injection of the superior mesenteric
artery and proximal and mid-splenic artery, and a 68Ga-DOTATATE positron emission
tomography/computed tomography showed focal uptake in the neck of the pancreas
with a standardized uptake value of 12. Despite negative intraoperative
pancreatic palpation and ultrasound, the patient underwent an extended distal
pancreatectomy with normalization of biochemical levels and resolution of her
symptoms. Pathology showed four subcentimeter neuroendocrine tumors that were
positive for insulin, consistent with a diagnosis of multiple microadenomas.
CONCLUSIONS: Multiple microadenomas are a rare cause of hyperinsulinemic
hypoglycemia and localization, and resection of these tumors may be facilitated
by multimodal imaging.
PMID- 27504853
TI - Quantitative model for the blood pressure-lowering interaction of valsartan and
amlodipine.
AB - AIMS: The objective of this study was to develop a population pharmacokinetic
(PK) and pharmacodynamic (PD) model to quantitatively describe the
antihypertensive effect of combined therapy with amlodipine and valsartan.
METHODS: PK modelling was used with data collected from 48 healthy volunteers
receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg
valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during
combined administration. SBP and DBP data for each drug alone were gathered from
the literature. PKPD models of each drug and for combined administration were
built with NONMEM 7.3. RESULTS: A two-compartment model with zero order
absorption best described the PK data of both drugs. Amlodipine and valsartan
monotherapy effects on SBP and DBP were best described by an Imax model with an
effect compartment delay. Combined therapy was described using a proportional
interaction term as follows: (D1 + D2 ) +ALPHA*(D1 * D2 ). D1 and D2 are the
predicted drug effects of amlodipine and valsartan monotherapy respectively.
ALPHA is the interaction term for combined therapy. Quantitative estimates of
ALPHA were -0.171 (95% CI: -0.218, -0.143) for SBP and -0.0312 (95% CI: -0.07739,
-0.00283) for DBP. These infra-additive interaction terms for both SBP and DBP
were consistent with literature results for combined administration of drugs in
these classes. CONCLUSION: PKPD models for SBP and DBP successfully described the
time course of the antihypertensive effects of amlodipine and valsartan. An infra
additive interaction between amlodipine and valsartan when used in combined
administration was confirmed and quantified.
PMID- 27504854
TI - Sex and pairing status explain variations in the activation of nonapeptide
receptors in song and motivation regions.
AB - The nonapeptides oxytocin and vasopressin have been implicated in a variety of
social behaviors. In zebra finches, oxytocin antagonists decrease pairing in both
sexes, and pairing, in turn, increases expression of both mesotocin (the avian
homologue of oxytocin) and vasotocin (the avian homologue of vasopressin).
Increases in mesotocin and vasotocin mRNA are correlated with the amount of
directed singing by males. Thus, in the present study, we examined the hypothesis
that activation of cells containing nonapeptide receptors in song-related regions
(ventral tegmental area, lateral septum, and medial preoptic nucleus) would also
be correlated with directed singing in males. To rule out the possibility that
these regions are involved in general pairing motivation, we also included
females as subjects. In the ventral tegmental area, males had higher ZENK and
V1aR than females and paired animals (regardless of sex) had higher ZENK and V1aR
than did unpaired animals. In the medial preoptic nucleus, paired animals had
higher ZENK than did unpaired animals, and there were no sex or pairing effects
in the lateral septum. Only ZENK + V1aR in the medial preoptic nucleus was
correlated with singing in males. These findings suggest that pairing is
associated activation of nonapeptide receptors in the ventral tegmental area and
the medial preoptic nucleus, but there is only partial evidence that courtship
singing accounts for these findings. (PsycINFO Database Record
PMID- 27504855
TI - Lipoprotein lipase in chronic lymphocytic leukemia: function and prognostic
implications.
AB - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
characterized by the accumulation of a clonal population of B cells in peripheral
blood, bone marrow, and lymphoid organs. More than 10 years ago, lipoprotein
lipase (LPL) mRNA was identified as being strongly expressed in patients
experiencing a more aggressive phenotype, while CLL patients with an indolent
disease course lack expression of this marker. Since then, several reports
confirmed the capability of LPL to predict CLL disease evolution at the moment of
diagnosis. In contrast, data on the functional implications of LPL in CLL are
scarce. LPL exerts a central role in overall lipid metabolism and transport, but
plays additional, non-catalytic roles as well. Which of those is more important
in the pathogenesis of CLL remains largely unclear. Here, we review the current
knowledge on the prognostic and biological relevance of LPL in CLL.
PMID- 27504856
TI - Further Evolution of Multifunctional Niosomes Based on Pluronic Surfactant: Dual
Active Targeting and Drug Combination Properties.
AB - The loading of chemotherapics into smart nanocarriers that simultaneously possess
more than one useful property for specifically targeting a tumor site improves
their therapeutic effectiveness, reducing their side effects. Hence, we proposed
a combined approach for the treatment of human breast cancer (BC) consisting of
the co-encapsulation of doxorubicin and curcumin or doxorubicin and quercetin
into multifunctional niosomes, which results in prolonged blood circulation and
an ability to spontaneously accumulate at the tumor site (passive target) and to
recognize and bind the tumor cells through dual ligand-receptor interactions
(active target). The drug-loaded vesicles showed high stability and good
capability of loading doxorubicin and antioxidants alone or in combination. Their
diameter was around 400 nm. The drugs released from the vesicles were found to be
controlled and sustained for over 24 h, with a strong dependence on the co
presence of the loaded molecules. Transferrin and/or folic acid were conjugated
on the external surface of the niosomes as ligands, considerably improving the
cellular uptake into MCF-7 and MDA-MB-231 malignant cells when compared with the
uptake of nonconjugated samples. In vitro evaluation of anticancer activity
demonstrated the strong potential of niosomes loaded with a doxorubicin/curcumin
combination as useful devices in breast tumor treatment. These features hold
great promise for the development of multifunctional devices that combine several
advantages such as biocompatibility, stealth properties, loading capability, and
active targeting, moving toward the development of more specific and efficient
carriers for personalized tumoral therapy.
PMID- 27504857
TI - Physics behind Water Transport through Nanoporous Boron Nitride and Graphene.
AB - In this work, molecular dynamics simulations were used to determine the surface
tension profile of water on graphene and boron nitride (BN) multilayers and to
predict water permeation through nanoporous graphene and BN membranes. For both
graphene and BN multilayers, a decrease in surface tension (gamma) was evidenced
as the number of layers increased. This lessening in gamma was shown to result
from a negative surface tension contribution due to long-range wetting of water,
which also contributes to lower water permeation through a two-layer membrane
with respect to permeation through a monolayer. We also showed that a decrease in
water surface tension on a BN monolayer with regards to graphene was at the
origin of an increase in water permeation through BN. Our findings suggest that
nanoporous BN membranes could be attractive candidates for desalination
applications.
PMID- 27504858
TI - Novel H2S Releasing Nanofibrous Coating for In Vivo Dermal Wound Regeneration.
AB - Hydrogen sulfide (H2S), together with nitric oxide and carbon monoxide, has been
recognized as an important gasotransmitter. It plays an essential physiological
role in regulating cyto-protective signal process, and H2S-based therapy is
considered as the next generation of promising therapeutic strategies for many
biomedical applications, such as the treatment of cardiovascular disease. Through
electrospinning of polycaprolactone (PCL) containing JK1, a novel pH-controllable
H2S donor, nanofibers with H2S releasing function, PCL-JK1, are fabricated. This
fibrous scaffold showed a pH-dependent H2S releasing behavior, i.e., lower pH
induced greater and faster H2S release. In addition, the H2S release of JK1 was
prolonged by the fibrous matrix as shown by decreased releasing rates compared to
JK1 in solutions. In addition, in vitro studies indicated that PCL-JK1 exhibited
excellent cyto-compatibility, similar to PCL fibers. Finally, we investigated PCL
JK1 as a wound dressing toward a cutaneous wound model in vivo and found that PCL
JK1 could significantly enhance the wound repair and regeneration compared with
the control PCL scaffold, likely due to the release of H2S, which results in a
broad range of physiologically protective functions toward the wound.
PMID- 27504859
TI - Comparative approaches to cortical microcircuits.
AB - Recent trends in neuroscience have narrowed the scope of this field, notably
through the progressive elimination of 'model systems' that were key to the
development of modern molecular, developmental and functional neuroscience.
Although the fantastic opportunities offered by modern molecular biology entirely
justify the use of selected organisms (e.g., for their genetic advantages), we
argue that a diversity of model systems is essential if we wish to identify the
brain's computational principles. It is through comparisons that we can hope to
separate mechanistic details (results of each organism's specific history) from
functional principles, those that will hopefully one day lead to a theory of the
brain.
PMID- 27504861
TI - Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation
and Reduced Glutathione Levels for Enhanced Photodynamic Therapy.
AB - Graphitic carbon nitride (g-C3 N4 ) has been used as photosensitizer to generate
reactive oxygen species (ROS) for photodynamic therapy (PDT). However, its
therapeutic efficiency was far from satisfactory. One of the major obstacles was
the overexpression of glutathione (GSH) in cancer cells, which could diminish the
amount of generated ROS before their arrival at the target site. Herein, we
report that the integration of Cu(2+) and g-C3 N4 nanosheets (Cu(2+) -g-C3 N4 )
led to enhanced light-triggered ROS generation as well as the depletion of
intracellular GSH levels. Consequently, the ROS generated under light irradiation
could be consumed less by reduced GSH, and efficiency was improved. Importantly,
redox-active species Cu(+) -g-C3 N4 could catalyze the reduction of molecular
oxygen to the superoxide anion or hydrogen peroxide to the hydroxyl radical, both
of which facilitated the generation of ROS. This synergy of improved ROS
generation and GSH depletion could enhance the efficiency of PDT for cancer
therapy.
PMID- 27504862
TI - Cutaneous presentation of Chagas' disease reactivation in a heart-transplant
patient.
PMID- 27504860
TI - A comparative approach to cerebellar function: insights from electrosensory
systems.
AB - Despite its simple and highly-ordered circuitry the function of the cerebellum
remains a topic of vigorous debate. This review explores connections between the
cerebellum and sensory processing structures that closely resemble the cerebellum
in terms of their evolution, development, patterns of gene expression, and
circuitry. Recent studies of cerebellum-like structures involved in
electrosensory processing in fish have provided insights into the functions of
granule cells and unipolar brush cells-cell types shared with the cerebellum. We
also discuss the possibility, supported by recent studies, that generating and
subtracting predictions of the sensory consequences of motor commands may be core
functions shared by both cerebellum-like structures and the cerebellum.
PMID- 27504864
TI - Risk factors for recurrent admissions with diabetic ketoacidosis: importance of
mental health.
PMID- 27504865
TI - The Effect of Muscarinic Receptor Modulators on the Antinociception Induced by
CB2 Receptor Agonist, JWH133 in Mice.
AB - There is no published study regarding the interaction between muscarinic receptor
modulators and antinociception induced by cannabinoid receptor (CB2) agonist. The
effect of pilocarpine (a muscarinic agonist) and atropine (a muscarinic
antagonist) on JWH-133 (a CB2 agonist) induced analgesia in mice was studied.
First the analgesic effect of JWH-133 (0.001-1 mg/Kg) or pilocarpine (2.5-20
mg/kg) or atropine (0.2-5 mg/kg) was evaluated. Subsequently, the effect of co
administration of pilocarpine (2.5 mg/kg) or atropine (5 mg/kg) and JWH-133
(0.001-1 mg/Kg) were studied too. JWH-133 and pilocarpine provoked
antinociception in mice but atropine did not. Pilocarpine potentiated the
analgesic effect of JWH-133 but atropine antagonized that. It can be concluded
that JWH-133 induced antinociception is affected by muscarinic receptor
modulators in mice.
PMID- 27504863
TI - Comparison of tibiofemoral joint space width measurements from standing CT and
fixed flexion radiography.
AB - The objective of this project was to determine the relationship between medial
tibiofemoral joint space width measured on fixed-flexion radiographs and the
three-dimensional joint space width distribution on low-dose, standing CT (SCT)
imaging. At the 84-month visit of the Multicenter Osteoarthritis Study, 20
participants were recruited. A commercial SCT scanner for the foot and ankle was
modified to image knees while standing. Medial tibiofemoral joint space width was
assessed on radiographs at fixed locations from 15% to 30% of compartment width
using validated software and on SCT by mapping the distances between three
dimensional subchondral bone surfaces. Individual joint space width values from
radiographs were compared with three-dimensional joint space width values from
corresponding sagittal plane locations using paired t-tests and correlation
coefficients. For the four medial-most tibiofemoral locations, radiographic joint
space width values exceeded the minimal joint space width on SCT by a mean of 2.0
mm and were approximately equal to the 61st percentile value of the joint space
width distribution at each respective sagittal-plane location. Correlation
coefficients at these locations were 0.91-0.97 and the offsets between joint
space width values from radiographs and SCT measurements were consistent. There
were greater offsets and variability in the offsets between modalities closer to
the tibial spine. Joint space width measurements on fixed-flexion radiographs are
highly correlated with three-dimensional joint space width from SCT. In addition
to avoiding bony overlap obscuring the joint, a limitation of radiographs, the
current study supports a role for SCT in the evaluation of tibiofemoral OA. (c)
2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
Res 35:1388-1395, 2017.
PMID- 27504866
TI - Potential Contribution of Antioxidant Mechanism in the Defensive Effect of
Lycopene Against Partial Sciatic Nerve Ligation Induced Behavioral, Biochemical
and Histopathological Modification in Wistar Rats.
AB - Neuropathic pain is a severe and unbearable condition which arises due to
activation of peripheral nociceptors after tissue damage, neuropathic pain is
caused from anomalous physiology of central or peripheral nervous system and it
may not be related to the ongoing tissue damage or inflammation. Involvement of
oxidative damage has been reported in the pathophysiology of neuropathic pain.
The purpose of this study was to examine the effect of lycopene to quench the
free radicals produced as a result of the increased oxidative stress in
neuropathic pain. Neuropathic pain was induced in wistar rats by partial sciatic
nerve ligation. The effect was evaluated by assessing various behavioral
parameters (thermal hyperalgesia, cold hyperalgesia), biochemical parameters
(lipid peroxidation, reduced glutathione, superoxide dismutase and catalase) as
well as histopathological parameters in sciatic nerve. During the experiment
group of 8 rats each was administered drugs once daily intraperitonealy (I.P.)
and naive groups, sham group and sciatic nerve ligated group were treated with
vehicle for the duration of 14 days. Partial sciatic nerve ligation (PSNL)
significantly caused thermal hyperalgesia, cold hyperalgesia and oxidative damage
compared to normal and sham groups. Daily administration of lycopene (25 mg/kg,
50 mg/kg) and gabapentin (100 mg/kg) considerably reversed hyperalgesia, cold
hyperalgesia and attenuated oxidative stress when compared to control group.
There was significant histological improvement in the in the architecture of
myelinated and unmyelinated fibers. The results indicated that free radical
generation mechanism might be involved in PSNL induced behavior, biochemical and
histopathological changes in wistar rats.
PMID- 27504867
TI - Efficacy of Full u-Opioid Receptor Agonists is not Impaired by Concomitant
Buprenorphine or Mixed Opioid Agonists/Antagonists - Preclinical and Clinical
Evidence.
AB - Buprenorphine and the mixed agonists/antagonists nalbuphine and pentazocine,
formerly classified as u-opioid (MOP) receptor antagonists, have more recently
been shown to be partial to full agonists of the human MOP receptor. These
receptors do not necessarily have to be maximally activated for a full
physiological response. Partial agonists can also sufficiently stimulate
signaling processes leading to a full analgesic response, as shown by the
effectiveness of buprenorphine, nalbuphine and pentazocine in animal pain models
and in clinical settings where these drugs induce analgesia with full efficacy
without a ceiling effect. Submaximal doses of MOP receptor analgesics combined
with submaximal doses of buprenorphine, pentazocine, or nalbuphine result in
additive to over-additive antinociceptive effects in animal experiments. Only
when doses are given that exceed the therapeutic dose range may the
antinociceptive effect be reduced to the effect of either opioid alone. The
analgesic effects of pentazocine and nalbuphine combined with morphine are
reported to be additive or over-additive in various clinical pain conditions.
Buprenorphine, which clinically behaves as a full MOP receptor agonist for pain
relief, can be combined with full opioid agonists without precipitating
withdrawal. Thus, the overall evidence on the analgesic effects of buprenorphine,
pentazocine or nalbuphine combined with opioid analgesics under various clinical
pain conditions contradicts the consensus that these compounds diminish MOP
receptor analgesia when co-administered with a full MOP receptor agonist.
PMID- 27504868
TI - Agomelatine and Transient Elevation of Creatine Phosphokinase.
AB - Agomelatine is an antidepressant drug with moderate agonistic action at the
melatonine receptor MT1 and weak effect at MT2. According to clinical studies,
agomelatine ameliorates depressive symptoms and improves sleep quality. Side
effects such as elevated liver enzymes are well-known. Therefore, routine
laboratory monitoring of liver function is recommended periodically throughout
treatment because of a rare risk of more serious liver reactions. 2 patients with
creatine phosphokinase elevation during treatment with agomelatine are presented.
We recommend a check of the creatine phosphokinase level during the initial
treatment phase in patients receiving agomelatine for the first time.
PMID- 27504869
TI - Construction of Chiral [4 + 4] and [2 + 2] Schiff-Base Macrocyclic Zinc(II)
Complexes Influenced by Counterions and Pendant Arms.
AB - Chiral and racemic 68-membered [4 + 4] tetranuclear and 34-membered [2 + 2]
dinuclear Schiff-base macrocyclic zinc(II) complexes 1-10 can be selectively
synthesized based on the secondary template effects of counterions and pendant
arms, when [(S,S), (R,R), (+/-)]-1,2-diaminocyclohexane precursors are first used
to react with a pair of extended dialdehydes with different pendant arms via
zinc(II) ion template-assisted imine condensation.
PMID- 27504870
TI - Phase I metabolism of the highly potent synthetic cannabinoid MDMB-CHMICA and
detection in human urine samples.
AB - Among the recently emerged synthetic cannabinoids, MDMB-CHMICA (methyl N-{[1
(cyclohexylmethyl)-1H-indol-3-yl]carbonyl}-3-methylvalinate) shows an
extraordinarily high prevalence in intoxication cases, necessitating analytical
methods capable of detecting drug uptake. In this study, the in vivo phase I
metabolism of MDMB-CHMICA was investigated using liquid chromatography
electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) and liquid
chromatography-electrospray ionization-quadrupole time-of-flight-mass
spectrometry (LC-ESI-Q ToF-MS) techniques. The main metabolites are formed by
hydrolysis of the methyl ester and oxidation of the cyclohexyl methyl side chain.
One monohydroxylated metabolite, the ester hydrolysis product and two further
hydroxylated metabolites of the ester hydrolysis product are suggested as
suitable targets for a selective and sensitive detection in urine. All detected
in vivo metabolites could be verified in vitro using a human liver microsome
assay. Two of the postulated main metabolites were successfully included in a
comprehensive LC-ESI-MS/MS screening method for synthetic cannabinoid
metabolites. The screening of 5717 authentic urine samples resulted in 818 cases
of confirmed MDMB-CHMICA consumption (14%). Since the most common route of
administration is smoking, smoke condensates were analyzed to identify relevant
thermal degradation products. Pyrolytic cleavage of the methyl ester and amide
bond led to degradation products which were also formed metabolically. This is
particularly important in hair analysis, where detection of metabolites is
commonly considered a proof of consumption. In addition, intrinsic activity of
MDMB-CHMICA at the CB1 receptor was determined applying a cAMP accumulation assay
and showed that the compound is a potent full agonist. Based on the collected
data, an enhanced interpretation of analytical findings in urine and hair is
facilitated. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27504871
TI - Transport phenomena of nanoparticles in plants and animals/humans.
AB - The interaction of a plethora nanoparticles with major biota such as plants and
animals/humans has been the subject of various multidisciplinary studies with
special emphasis on toxicity aspects. However, reports are meager on the
transport phenomena of nanoparticles in the plant-animal/human system. Since
plants and animals/humans are closely linked via food chain, discussion is
imperative on the main processes and mechanisms underlying the transport
phenomena of nanoparticles in the plant-animal/human system, which is the main
objective of this paper. Based on the literature appraised herein, it is
recommended to perform an exhaustive exploration of so far least explored aspects
such as reproducibility, predictability, and compliance risks of nanoparticles,
and insights into underlying mechanisms in context with their transport
phenomenon in the plant-animal/human system. The outcomes of the suggested
studies can provide important clues for fetching significant benefits of rapidly
expanding nanotechnology to the plant-animal/human health-improvements and
protection as well.
PMID- 27504872
TI - Immunomodulatory effects of exposure to polychlorinated biphenyls and
perfluoroalkyl acids in East Greenland ringed seals (Pusa hispida).
AB - To better elucidate the potential immune-related health effects of exposure to
environmentally persistent organic pollutants (POP), such as polychlorinated
biphenyls (PCBs) and perfluoroalkyl substances (PFASs), in ringed seals (Pusa
hispida), a sentinel Arctic species, we assessed 1) associations between mitogen
induced lymphocyte proliferation and in vivo tissue contaminant burdens, and 2)
the concentration-response effects of in vitro exposure to PFASs and PCB
congeners on mitogen-induced lymphocyte proliferation. Upon in vitro contaminant
exposure, the non-coplanar PCB congeners CB 138, 153, and 180, but not the
coplanar CB 169, significantly reduced lymphocyte proliferation between 10 and
20ugg-1 ww. The respective in vitro EC50 values for these congeners were 13.3,
20.7, 20.8, and 54.6ugg-1 ww. No modulation of lymphocyte proliferation was
observed upon in vitro exposure to two individual PFASs, perfluorooctane
sulphonic acid (PFOS) and perfluorooctanoic acid (PFOA), at concentrations up to
1000ngg-1. In addition, no significant correlations were found between lymphocyte
proliferation and any blood or blubber contaminant measured. Taken together,
these data suggest this population of ringed seals is not currently at high risk
of altered lymphocyte proliferation from exposure to the POPs or PFASs in this
study.
PMID- 27504873
TI - Human exposure to endocrine disrupting compounds: Their role in reproductive
systems, metabolic syndrome and breast cancer. A review.
AB - Endocrine disrupting chemicals (EDCs) are released into the environment from
different sources. They are mainly used in packaging industries, pesticides and
food constituents. Clinical evidence, experimental models, and epidemiological
studies suggest that EDCs have major risks for humans by targeting different
organs and systems in the body (e.g. reproductive system, breast tissue, adipose
tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds
the aim of this review is to describe the most recent data on the effects induced
by phthalates, bisphenol A and parabens in a critical window of exposure: in
utero, during pregnancy, infants, and children. The interactions and mechanisms
of toxicity of EDCs in relation to human general health problems, especially
those broadening the term of endocrine disruption to 'metabolic disruption',
should be deeply investigated. These include endocrine disturbances, with
particular reference to reproductive problems and breast, testicular and ovarian
cancers, and metabolic diseases such as obesity or diabetes.
PMID- 27504875
TI - Understanding the bereavement care roles of nurses within acute care: a
systematic review.
AB - AIMS AND OBJECTIVES: To investigate nurses' roles and responsibilities in
providing bereavement care during the care of dying patients within acute care
hospitals. BACKGROUND: Bereavement within acute care hospitals is often sudden,
unexpected and managed by nurses who may have limited access to experts. Nurses'
roles and experience in the provision of bereavement care can have a significant
influence on the subsequent bereavement process for families. Identifying the
roles and responsibilities, nurses have in bereavement care will enhance
bereavement supports within acute care environments. DESIGN: Mixed-methods
systematic review. METHODS: The review was conducted using the databases
Cumulative Index Nursing and Allied Health Literature Plus, Embase, Ovid MEDLINE,
PsychINFO, CareSearch and Google Scholar. Included studies published between 2006
2015, identified nurse participants, and the studies were conducted in acute care
hospitals. Seven studies met the inclusion criteria, and the research results
were extracted and subjected to thematic synthesis. RESULTS: Nurses' role in
bereavement care included patient-centred care, family-centred care, advocacy and
professional development. Concerns about bereavement roles included competing
clinical workload demands, limitations of physical environments in acute care
hospitals and the need for further education in bereavement care. CONCLUSIONS:
Further research is needed to enable more detailed clarification of the roles
nurse undertake in bereavement care in acute care hospitals. There is also a need
to evaluate the effectiveness of these nursing roles and how these provisions
impact on the bereavement process of patients and families. RELEVANCE TO CLINICAL
PRACTICE: The care provided by acute care nurses to patients and families during
end-of-life care is crucial to bereavement. The bereavement roles nurses
undertake are not well understood with limited evidence of how these roles are
measured. Further education in bereavement care is needed for acute care nurses.
PMID- 27504874
TI - Risk and impact of pulmonary complications in survivors of childhood cancer: A
report from the Childhood Cancer Survivor Study.
AB - BACKGROUND: Pulmonary complications after cancer therapy are varied. This study
describes pulmonary outcomes among childhood cancer survivors and evaluates their
impact on daily activities. METHODS: The incidence of pulmonary outcomes (asthma,
chronic cough, emphysema, lung fibrosis, oxygen need, and recurrent pneumonia)
reported among 5-year cancer survivors (n = 14,316) and the incidence of death
due to pulmonary causes among all eligible survivors (n = 20,690) in the
Childhood Cancer Survivor Study were compared with those for sibling controls (n
= 4027) with cumulative incidence, standardized mortality ratio (SMR), and
piecewise exponential models. Logistic regression with random effects was used to
estimate odds ratios (ORs) and 95% confidence intervals (CIs) for activity
limitations with pulmonary complications. RESULTS: By the age of 45 years, the
cumulative incidence of any pulmonary condition was 29.6% (95% CI, 29.1%-30.0%)
for cancer survivors and 26.5% (95% CI, 24.9%-28.0%) for siblings. Fewer
survivors reported ever smoking (23.6% vs 36.4%, P < .001), but survivors were
more likely to report chronic cough (rate ratio [RR], 1.6; 95% CI, 1.4-1.9),
oxygen need (RR, 1.8; 95% CI, 1.5-2.2), lung fibrosis (RR, 3.5; 95% CI, 2.3-5.4),
and recurrent pneumonia (RR, 2.0; 95% CI, 1.4-3.0). The SMR for death due to
pulmonary causes was 5.9 (95% CI, 4.2-8.1), and it was associated with platinum
exposure and lung radiation (P < .01). The impact of chronic cough on daily
activities for survivors (OR vs survivors without chronic cough, 2.7) was greater
than that for siblings (OR, 2.0; P = .04). CONCLUSIONS: Pulmonary complications
are substantial among adult survivors of childhood cancer and can affect daily
activities. Cancer 2016;122:3687-96. (c) 2016 American Cancer Society.
PMID- 27504876
TI - Relevance of New Definitions to Incidence and Prognosis of Acute Kidney Injury in
Hospitalized Patients with Cirrhosis: A Retrospective Population-Based Cohort
Study.
AB - BACKGROUND: The implementation of new serum creatinine (SCr)-based criteria for
acute kidney injury (AKI) has brought to light several areas of uncertainty in
patients with cirrhosis. STUDY DESIGN: Population-based cohort study. SETTING &
PARTICIPANTS: Adults with cirrhosis hospitalized between 2002-2012. PREDICTOR: We
aimed to address the prognostic implications of the new AKI criteria in
cirrhosis. OUTCOMES: Baseline kidney function was defined from all outpatient SCr
within 3 months before hospitalization. Cox proportional hazards models were fit
to examine associations between AKI, renal recovery and all-cause mortality.
RESULTS: 4,733 patients were studied. The 30-day mortality was higher for
participants with AKI (43.9% vs 8.5%; p-value<0.001), and increased with AKI
severity. The highest incidence of AKI occurred when the lowest SCr within the
three months prior to admission was used to define baseline. The hazard ratio for
mortality using the lowest SCr within 3 months and the closest pre-admission SCr
(definition suggested by the recent consensus guideline) were similar, validating
the use of the latter measure. As compared to patients without AKI, stage 1 AKI
with maximum SCr <=132 mmol/L remained associated with a 3.5-fold increased
hazard of death at 30 days (95% CI 2.6 to 4.7). LIMITATIONS: As an observational
study, the results were vulnerable to residual confounding and ascertainment bias
in the use of laboratory data to identify AKI. We did not have access to liver
function or disease etiology variables and were unable to adjust for these in our
analyses. CONCLUSIONS: These results confirm the graded relationship between AKI
severity, renal recovery, and mortality and further clarify previously discordant
reports about the prognostic relevance of new AKI criteria in patients with
cirrhosis.
PMID- 27504878
TI - Longitudinal Predictors of Outcomes for Adults With Autism Spectrum Disorder:
Systematic Review.
AB - To generate an evidence-based understanding of longitudinal predictors of social
outcomes (i.e., employment, social relationships/participation, independent
living) of adults with autism spectrum disorder (ASD), we conducted a systematic
literature review of publications since 2000. Twelve publications deriving from
eight study samples fit inclusion/exclusion criteria for the review. In these
publications, statistically significant predictors of social outcomes fell into
five categories: (a) personal characteristics, (b) individual functioning, (c)
family context, (d) services, and (e) other factors (i.e., peer influence, health
status). However, only two studies demonstrated high methodological quality, and
only one category of predictors-individual functioning-was identified across
multiple study samples. To inform practices for youth with ASD, there remains a
need for high-quality outcome research related to adults with ASD to better
understand predictors, especially related to environmental factors such as
related to the family and services received.
PMID- 27504877
TI - Identification and Functional Testing of ERCC2 Mutations in a Multi-national
Cohort of Patients with Familial Breast- and Ovarian Cancer.
AB - The increasing application of gene panels for familial cancer susceptibility
disorders will probably lead to an increased proposal of susceptibility gene
candidates. Using ERCC2 DNA repair gene as an example, we show that proof of a
possible role in cancer susceptibility requires a detailed dissection and
characterization of the underlying mutations for genes with diverse cellular
functions (in this case mainly DNA repair and basic cellular transcription). In
case of ERCC2, panel sequencing of 1345 index cases from 587 German, 405
Lithuanian and 353 Czech families with breast and ovarian cancer (BC/OC)
predisposition revealed 25 mutations (3 frameshift, 2 splice-affecting, 20
missense), all absent or very rare in the ExAC database. While 16 mutations were
unique, 9 mutations showed up repeatedly with population-specific appearance. Ten
out of eleven mutations that were tested exemplarily in cell-based functional
assays exert diminished excision repair efficiency and/or decreased
transcriptional activation capability. In order to provide evidence for BC/OC
predisposition, we performed familial segregation analyses and screened
ethnically matching controls. However, unlike the recently published RECQL
example, none of our recurrent ERCC2 mutations showed convincing co-segregation
with BC/OC or significant overrepresentation in the BC/OC cohort. Interestingly,
we detected that some deleterious founder mutations had an unexpectedly high
frequency of > 1% in the corresponding populations, suggesting that either
homozygous carriers are not clinically recognized or homozygosity for these
mutations is embryonically lethal. In conclusion, we provide a useful resource on
the mutational landscape of ERCC2 mutations in hereditary BC/OC patients and, as
our key finding, we demonstrate the complexity of correct interpretation for the
discovery of "bonafide" breast cancer susceptibility genes.
PMID- 27504879
TI - Item-Level Psychometrics of the Glasgow Outcome Scale: Extended Structured
Interviews.
AB - The Glasgow Outcome Scale-Extended (GOSE) structured interview captures critical
components of activities and participation, including home, shopping, work,
leisure, and family/friend relationships. Eighty-nine community dwelling adults
with mild-moderate traumatic brain injury (TBI) were recruited (average = 2.7
year post injury). Nine items of the 19 items were used for the psychometrics
analysis purpose. Factor analysis and item-level psychometrics were investigated
using the Rasch partial-credit model. Although the principal components analysis
of residuals suggests that a single measurement factor dominates the measure, the
instrument did not meet the factor analysis criteria. Five items met the rating
scale criteria. Eight items fit the Rasch model. The instrument demonstrated low
person reliability (0.63), low person strata (2.07), and a slight ceiling effect.
The GOSE demonstrated limitations in precisely measuring activities/participation
for individuals after TBI. Future studies should examine the impact of the low
precision of the GOSE on effect size.
PMID- 27504880
TI - Life Balance and Stress in Adults With Medical Conditions or Obesity.
AB - This cross-sectional research examined differences in life balance and perceived
stress by body mass index (BMI) levels and self-reported medical conditions that
limited physical activity. The sample consisted of 2,338 participants between the
ages of 18 and 49 years who took the Life Balance Inventory, the Perceived Stress
Scale, and provided demographic information including height and weight. Findings
showed that individuals who were obese (BMI > 30.0) reported significantly lower
life balance scores and higher stress scores than participants without obesity (p
< .001). Also, individuals who had medical conditions that resulted in activity
limitations reported significantly less life balance and more stress than
individuals without medical conditions (p < .001). These findings highlight the
importance of addressing activity participation as a means to promote health and
wellness.
PMID- 27504881
TI - Developing a Canadian-Specific Version of the Fitness-to-Drive Screening
Measure(c).
AB - The Fitness-to-Drive Screening Measure((c)) (FTDS) is a valid and reliable
screening tool that identifies at-risk older drivers. Although 12,300 Canadians
have used the FTDS in the last 2 years, the resources/recommendations targeted
the U.S. CONTEXT: The objective of this article is to identify the FTDS
resources/recommendations appropriate for Canadian users and the barriers that
Canadian stakeholders experience when promoting older driver fitness. Twenty
stakeholders from three provinces (eight occupational therapists, three certified
driver rehabilitation specialists, four physicians, and five members of advocacy
organizations) participated in semi-structured interviews. We conducted summative
and thematic content analysis. A comprehensive set of resources/recommendations
was identified. Barriers to older driver fitness decisions included fear of
losing the license, compromising the physician-client relationship, insufficient
training/resources for health care professionals, and inadequate alternative
transportation. Canadian context-specific resources/recommendations were
integrated into a Canadian version of the FTDS. This version may better serve
Canadian older drivers, caregivers, and health care professionals.
PMID- 27504882
TI - Integrating the Science of Habit: Opportunities for Occupational Therapy.
AB - Chronic diseases are the leading causes of early morbidity and mortality in the
United States. Because personal behaviors are the primary risk factors for
developing chronic diseases, developing effective strategies to modify personal
behaviors remains a national imperative. Occupational therapy can help address
this problematic situation through interventions based on an understanding of
habit and principles of habit modification. The objective of this paper is to
provide an evidence-based argument for occupational therapy research and practice
targeting health-promoting lifestyle behaviors as habits. We discuss empirical
research conducted over the previous decade with a focus on the role of habit in
daily behavior, key evidence-based strategies for changing existing habits and
developing new habits, and recent advances in habit measurement in relation to
issues of intervention design. Understanding habit development, function, and
change offers a novel orientation for occupational therapy toward practice and
research on many complex health problems.
PMID- 27504884
TI - [Impact of entry age and veterinary care on health and performance of veal
calves. I. Mortality and antimicrobial use].
AB - INTRODUCTION: The objective of this field study was to describe the impact of the
entry age and intensive veterinary care on mortality and antimicrobial use of
veal calves in Switzerland. From July until October 2012, a total of 316 young
calves (aged o 10.8 days) and from November 2012 until May 2013 a total of 425
market calves (aged o 39.5 days) were housed on a welcome-farm, where they
obtained daily veterinary care during the first 6 weeks of the production cycle.
As a 3rd category 2 groups of 34 and 31 old calves (aged o 61.5 days),
respectively, were housed on a commercial farm. From entry to slaughter the daily
doses of antibiotics on group level averaged 35.6 in young calves, 26.2 in
commercial calves, and 21.0 in old calves. On the welcome-farm 45.9% and 48.5% of
the young and market calves, respectively, were individually treated, and in the
finishing period of the production cycle 10.4% and 3.3% of the young and market
calves, respectively. Of the old calves 16.9% were individually treated.
Mortality was 6.7% in young calves, 8.2% in commercial calves, and 4.6% in old
calves. Intensive veterinary care guaranteed early recognition of disease and
euthanasia of terminally morbid calves. The different entry ages did not lead to
any reduction in mortality or in antimicrobial use compared to previous studies.
PMID- 27504885
TI - [Impact of the entry age and veterinary care on the health and performance of
veal calves. II. Blood values, performance and carcass quality].
AB - INTRODUCTION: The objective of this field study was to investigate the impact of
the entry age and of veterinary care on blood values, performance and carcass
quality of veal calves in Switzerland. From July 2012 until May 2013 a total of
316 young calves (aged o 10.8 days), 425 market calves (aged o 39.5 days), and 65
old calves (aged o 61.5 days) were observed during the production cycle. As
control calves 9'019 veal calves fattened at the same time as the market calves
were available. At time of entry the average hemoglobin value of 88.2 g/l in
market calves was significantly (p < 0.001) lower than in young (96.2 g/l), old
(95.0 g/l) and control calves (95.0 g/l). At time of slaughter the hemoglobin of
control calves was 101.2 g/l and significantly (p < 0.001) lower than in young
(129.6 g/l) and market calves (131.6 g/l). The average daily weight gain reached
1.21 kg in young calves, 1.28 kg in market calves, 1.29 kg in old calves and 1.30
kg in control calves. The premature slaughter rate was 3.4% in control calves,
8.1% young (p < 0.001), 3.4% in commercial and 0% in old calves (p = 0.17). The
percentage of the favorite carcass quality was 53.8% in control calves and
differed significantly (p < 0.001) from young (43.5%) and market calves (42.8%),
but not from old calves (50.8%, p = 0.9). The carcass color with the average
photometric L-value of 41.5 in young and 41.6 in market calves differed
significantly (p < 0.001) from old (44.4) and control calves (45.4). The
intensive veterinary care and the different entry ages had no positive effect on
performance and carcass quality. The iron supply resulted in increased hemoglobin
values and in reddish carcass color in more than 50% of the investigated calves.
PMID- 27504886
TI - Evaluation of antimicrobial activity of Italian honey for wound healing
application in veterinary medicine.
AB - INTRODUCTION: Honey as a topical treatment for infected wounds dates back to
ancient times. However, few studies have been reported concerning the medical
properties of Italian honey. In this study, the microbial contamination, the
antimicrobial activity and the antibiotic residues of 6 different varieties of
Piedmont honeys were evaluated. The antimicrobial activity of honeys was tested
by agar well diffusion method and 1 honey for each variety has been selected and
tested by broth micro-dilution test to determine Minimum Inhibitory
Concentrations (MICs) and evaluated by Minimum Bactericidal Concentrations
(MBCs). The honeys with a high level of antibacterial activity were analyzed for
the presence of tetracyclines, sulfonamides and macrolide residues. The agar well
diffusion method showed the greatest antimicrobial activity for honeydew,
chestnut and lime tree honeys. The MICs and MBCs identified the close similarity
to the medical manuka honey of honeydew, polyfloral and chestnut honey. The
levels of antibiotic residues on these honeys were below the limit of
quantification. Based on our results the Italian variety of honeydew showed the
best antimicrobial activity and can be considered for the treatment of infected
wounds in animals.
PMID- 27504887
TI - Outbreak of sheeppox in farmed sheep in Kyrgystan: Histological, eletron
microscopical and molecular characterization.
AB - INTRODUCTION: On a farm in the Kyrgyz Republic, several dead sheep were found
without any history of illness. The sheep showed several ulcerations on lips and
bare-skinned areas. At necropsy the lungs showed multiple firm nodules, which
were defined as pox nodules histologically. In the rumen hyperkeratotic plaques
were visible. With electron microscopy pox viral particles were detected and
confirmed with q PCR as Capripoxviruses. Although all members of the
Capripoxvirus genus are eradicated in western countries, this study should remind
us of the classical lesions observed in poxvirus infections.
PMID- 27504888
TI - Epidemiology of Parkinson's Disease: A Population-Based Study in Primary Care in
Italy.
AB - BACKGROUND: There are no studies on prevalence, incidence and comorbidities of
Parkinson's disease (PD) in the Italian population. METHODS: The database of 700
Italian general practitioners (population, 923,356) was investigated. All
patients with International Classification of Diseases Ninth Revision - Clinical
Modification (ICD-9-CM) diagnosis of PD during the period 2002-2012 were
included. Parkinsonisms were excluded. Clinical conditions preceding PD were
identified through ICD-9-CM codes. The Charlson Comorbidity Index was used. PD
crude and standardized prevalence and annual incidence were calculated. Crude and
adjusted hazard ratios were calculated for comorbidities. RESULTS: A total of
2,204 patients (1,140 men, 1,064 women, age 22-95 years) were included. The crude
prevalence of PD was 239/100,000. Prevalence increased exponentially with age.
Standardized prevalence was 233 (95% CI 232-235). One hundred ninety-four
patients were newly diagnosed, giving a crude incidence of 22/100,000 and a
standardized incidence of 23.1/100,000 (95% CI 22.9-23.2). Incidence increased
steadily until age 75-84 years and then decreased. Older age, cardiovascular and
gastrointestinal disorders, diabetes, and restless-legs syndrome were associated
with increased PD risk and smoking and hypersomnia with decreased PD risk. The
Charlson Comorbidity Index was associated with PD risk with a documented
gradient. CONCLUSIONS: Prevalence and incidence of PD in Italy are in line with
studies with the highest case ascertainment. PD risk varies with the number and
type of comorbidities.
PMID- 27504889
TI - Examining the Feasibility and Predictive Validity of the SAGAT Tool to Assess
Situation Awareness Among Medical Trainees.
AB - INTRODUCTION: Situational awareness (SA) describes a team's ability to perceive
environmental elements, comprehend their meaning, and anticipate future events.
Although SA is consistently described as a critical competency among surgical
teams, there is a dearth of research identifying efficacious methods to assess
and develop SA in such settings. The aim of this study was to investigate the
feasibility of implementing an objective tool that has been used to measure SA in
other intense and dynamic environments -the Situation Awareness Global Assessment
Technique (SAGAT)-and to examine its ability to predict surgical trainee team
performance. METHODS: Ten team-training sessions were conducted involving 2
standardized high-fidelity trauma simulation scenarios. Teams consisted of 4 or 5
participants, and roles were randomly assigned. Team situational awareness was
assessed using the SAGAT method, which involves intermittent freezes to probe
trainee awareness of the situation. Team performance was assessed using the Mayo
High-Performance Teamwork Scale. Hierarchical regression was used to examine SA
performance relationships for each scenario. RESULTS: Forty-three third-year
medical students participated in the training sessions. Team SA ranged from 45%
to 79% and 46% to 97% for the first and second scenarios, respectively.
Additionally, team SA significantly predicted team performance for both the first
scenario (F(1, 42)=19.57; P<0.001; R=0.30) and second scenario (F(1,42)=26.18,
P<0.001; R=0.38). CONCLUSIONS: The SAGAT is a valid, reliable tool for assessing
surgical trainee SA. Information provided by the SAGAT can help diagnose team
performance problems, inform debriefing discussion points, and inform curriculum
development endeavors.
PMID- 27504890
TI - Improving Nurses' Peripheral Intravenous Catheter Insertion Knowledge,
Confidence, and Skills Using a Simulation-Based Blended Learning Program: A
Randomized Trial.
AB - INTRODUCTION: Peripheral intravenous catheter (PIVC) insertion is one of the most
common invasive procedures performed in a hospital, but most nurses receive
little formal training in this area. Blended PIVC insertion training programs
that incorporate deliberate simulated practice have the potential to improve
clinical practice and patient care. METHODS: The study was a randomized, wait
list control group with crossover using nurses on three medical/surgical units.
Baseline PIVC knowledge, confidence, and skills assessments were completed for
both groups. The intervention group then received a 2-hour PIVC online course,
followed by an 8-hour live training course using a synergistic mix of three
simulation tools. Both groups were then reassessed. After crossover, the wait
list group received the same intervention and both groups were reassessed.
RESULTS: At baseline, both groups were similar for knowledge, confidence, and
skills. Compared with the wait-list group, the intervention group had
significantly higher scores for knowledge, confidence, and skills upon completing
the training program. After crossover, the wait-list group had similarly higher
scores for knowledge, confidence, and skills than the intervention group. Between
the immediate preintervention and postintervention periods, the intervention
group improved scores for knowledge by 31%, skills by 24%, and decreased
confidence by 0.5%, whereas the wait-list group improved scores for knowledge by
28%, confidence by 16%, and skills by 15%. CONCLUSIONS: Results demonstrate
significant improvements in nurses' knowledge, confidence, and skills with the
use of a simulation-based blended learning program for PIVC insertion.
Transferability of these findings from a simulated environment into clinical
practice should be further explored.
PMID- 27504891
TI - Multifunctional Magnetoliposomes for Sequential Controlled Release.
AB - The simultaneous or sequential delivery of multiple therapeutic active principles
to a specific target is one of the main challenges of nanomedicine. This goal
requires the construction of complex devices often extremely time and cost
consuming. Supramolecular self-assemblies, with building blocks of different
nature, each providing a specific function to the final construct, can combine a
facile synthetic route with a high tunability and structural control. In this
study we provide the proof-of-principle of a drug delivery system, DDS,
constituted of (i) liposomes, providing a fully biocompatible lipid scaffold
suitable to host both hydrophobic and hydrophilic drugs; (ii) a double-stranded
DNA conjugated with a cholesteryl unit that spontaneously inserts into the lipid
membrane; and (iii) hydrophobic and hydrophilic superparamagnetic iron oxide
nanoparticles (SPIONs) embedded inside the lipid membrane of liposomes or
connected to the DNA, respectively. Upon application of an alternating magnetic
field, the SPIONs can trigger, through thermal activation, the release of a DNA
strand or of the liposomal payload, depending on the frequency and the
application time of the field, as proved by both steady-state and time-resolved
fluorescence studies. This feature is due to the different localization of the
two kinds of SPIONS within the construct and demonstrates the feasibility of a
multifunctional DDS, built up from self-assembly of biocompatible building
blocks.
PMID- 27504892
TI - Genetic Differentiation, Isolation-by-Distance, and Metapopulation Dynamics of
the Arizona Treefrog (Hyla wrightorum) in an Isolated Portion of Its Range.
AB - Population attributes such as diversity, connectivity, and structure are
important components of understanding species persistence and vulnerability to
extinction. Hyla wrightorum, the Arizona treefrog, is native to the southwestern
United States and Mexico, and an isolated group of populations exists in the
Huachuca Mountains and Canelo Hills (HMCH) of southeastern Arizona, USA. Due to
concerns about declining observations of the species within the isolated HMCH
portion of its range, the HMCH group is currently a candidate for federal
protection under the U.S. Endangered Species Act. We present results of a genetic
study examining population diversity, structure, and connectivity within the HMCH
region. We sampled DNA from H. wrightorum larvae and adults from ten distinct
locations, 8 of which were breeding sites and 4 of which were previously
undescribed localities for the species. We developed and genotyped 17 polymorphic
microsatellite loci and quantified genetic diversity, population differentiation,
and landscape influences on population genetic structure. We found evidence of
larger than expected effective population sizes, significant genetic
differentiation between populations, and evidence of distance being the primary
driver of genetic structure of populations with some influence of slope and
canopy cover. We found little evidence of recent genetic bottlenecks, and
individual-based analyses indicate admixture between populations despite
significant genetic differentiation. These patterns may indicate that the
breeding sites within the Huachuca Mountains constitute a metapopulation. We
suggest that the HMCH region may contain larger and more connected breeding
populations than previously understood, but the dynamics of this system and the
limited geographic extent of the HMCH group justify current concern for the
persistence of the species in this region. Efforts to ensure availability of high
quality breeding habitats and control for local threats such as effects of
invasive predators may be critical to the persistence of these unique populations
of H. wrightorum.
PMID- 27504893
TI - Differential microRNA Expression and Regulation in the Rat Model of Post
Infarction Heart Failure.
AB - BACKGROUND: Heart failure is a complex end stage of various cardiovascular
diseases with a poor prognosis, and the mechanisms for development and
progression of heart failure have always been a hot point. However, the molecular
mechanisms underlying the post transcriptional regulation of heart failure have
not been fully elucidated. Current data suggest that microRNAs (miRNAs) are
involved in the pathogenesis of heart failure and could serve as a new biomarker,
but the precise regulatory mechanisms are still unclear. METHODS: The
differential miRNA profile in a rat model of post-infarction heart failure was
determined using high throughout sequencing and analyzed through bioinformatics
approaches. The results were validated using qRT-PCR for 8 selected miRNAs. Then
the expression patterns of 4 miRNAs were analyzed in different periods after
myocardial infarction. Finally, gain- and loss-of-function experiments of rno-miR
122-5p and rno-miR-184 were analyzed in H2O2 treated H9c2 cells. RESULTS: In the
heart failure sample, 78 miRNAs were significantly upregulated and 28 were
downregulated compared to the controls. GO and KEGG pathway analysis further
indicated the likely roles of these miRNAs in heart failure. Time-course analysis
revealed different expression patterns of 4 miRNAs: rno-miR-122-5p, rno-miR-199a
5p, rno-miR-184 and rno-miR-208a-3p. Additionally, rno-miR-122-5p and rno-miR-184
were proved to promote apoptosis in vitro. CONCLUSIONS: Differential profile and
expression patterns of miRNAs in the rats model of post-infarction heart failure
were found, and the pro-apoptotic roles of rno-miR-122-5p and rno-miR-184 were
revealed. These findings may provide a novel way that may assist in heart failure
diagnosis and treatment.
PMID- 27504894
TI - Developmental Toxicity of Zinc Oxide Nanoparticles to Zebrafish (Danio rerio): A
Transcriptomic Analysis.
AB - Zinc oxide nanoparticles (ZnO NPs) are being utilized in an increasing number of
fields and commercial applications. While their general toxicity and associated
oxidative stress have been extensively studied, the toxicological pathways that
they induce in developmental stages are still largely unknown. In this study, the
developmental toxicity of ZnO NPs to embryonic/larval zebrafish was investigated.
The transcriptional expression profiles induced by ZnO NPs were also investigated
to ascertain novel genomic responses related to their specific toxicity pathway.
Zebrafish embryos were exposed to 0.01, 0.1, 1, and 10 mg/L ZnO NPs for 96 h post
fertilization. The toxicity of ZnO NPs, based on their Zn concentration, was
quite similar to that in embryonic/larval zebrafish exposed to corresponding
ZnSO4 concentrations. Pericardial edema and yolk-sac edema were the principal
malformations induced by ZnO NPs. Gene-expression profiling using microarrays
demonstrated 689 genes that were differentially regulated (fold change >1.5)
following exposure to ZnO NPs (498 upregulated, 191 downregulated). Several genes
that were differentially regulated following ZnO NP exposure shared similar
biological pathways with those observed with ZnSO4 exposure, but six genes
(aicda, cyb5d1, edar, intl2, ogfrl2 and tnfsf13b) associated with inflammation
and the immune system responded specifically to ZnO NPs (either in the opposite
direction or were unchanged in ZnSO4 exposure). Real-time reverse-transcription
quantitative polymerase chain reaction confirmed that the responses of these
genes to ZnO NPs were significantly different from their response to ZnSO4
exposure. ZnO NPs may affect genes related to inflammation and the immune system,
resulting in yolk-sac edema and pericardia edema in embryonic/larval
developmental stages. These results will assist in elucidating the mechanisms of
toxicity of ZnO NPs during development of zebrafish.
PMID- 27504895
TI - Electronic and Photophysical Properties of [Re (L)(CO)3(phen)](+) and
[Ru(L)2(bpy)2](2+) (L = imidazole), Building Units for Long-Range Electron
Transfer in Modified Blue Copper Proteins.
AB - The electronic, optical, and photophysical properties of [Re(im)(CO)3(phen)](+)
and [Ru(bpy)2(im)2](2+) (im = imidazole; phen = 1,10-phenanthroline; bpy = 2,2'
bipyridine) in water, including spin-orbit coupling (SOC) effects, were studied
by means of density functional theory (DFT) and time-dependent DFT. The main
features of the visible experimental absorption spectra of both molecules are
well-reproduced. Whereas the theoretical spectrum of the Re(I) complex is
characterized by one metal-to-ligand charge transfer (MLCTphen) state of low
intensity at 394 nm and a strongly absorbing MLCTphen state calculated at 370 nm,
the spectrum of the Ru(II) complex presents a high density of singlet MLCTbpy
excited states with significant oscillator strengths that contribute to the two
broad bands centered at 490 and 340 nm. The absorption spectrum of [Re(im)
(CO)3(phen)](+) is perturbed by SOC with non-negligible mixing between the low
lying triplet and singlet absorbing states, while SOC has no effect on the
absorption spectrum of [Ru(bpy)2(im)2](2+). A detailed structural investigation
of the two lowest singlet and four lowest triplet excited states of the Re(I)
complex point to MLCTphen (S1, S2, T1, T2) and intra-ligand ILphen (T3) localized
spin-densities characterized by small contractions from both Re-N and phen CC
central bonds in the MLCT states and nearly no deformation in the IL state. A
mechanism of luminescent decay of [Re(im) (CO)3(phen)](+) is proposed on the
basis of the calculated energy minima and wavelengths of emission for the
interpretation of the three frequency/time-scale signals put in evidence by
ultrafast experiments. The long-lived emissive properties of [Ru(bpy)2(im)2](2+)
are analyzed on the basis of the relative energies of the two lowest (3)MLCTbpy
and metal-centered (3)MC excited states. The minimum corresponding to the (3)MC
spin density shows a significant structural rearrangement with an increase of the
Ru-N bond distance of 0.33 A and a closure of the N-Ru-N bond angle of 20 degrees
inducing a large distortion of the octahedral motif. The spin-density associated
with the lowest (3)MLCTbpy localized on one bpy ligand suggests the presence of a
second degenerate (3)MLCTbpy minimum. The luminescence of the Ru(II) complex
calculated at 669 nm is partially quenched by the presence of the low (3)MC
nonradiative state at 1064 nm. When interacting with modified metal-based
proteins the two complexes will behave differently because of these distinctive
photophysical properties.
PMID- 27504896
TI - Deep Brain Stimulation for Status Dystonicus: A Case Series and Review of the
Literature.
AB - BACKGROUND: Status dystonicus (SD) is a rare and potentially life-threatening
complication of primary or secondary dystonia, characterized by acute worsening
of dystonic movements. There is no consensus regarding optimal treatment, which
may be medical and/or surgical. METHODS: We present our experience with pallidal
deep brain stimulation (DBS) in 5 DYT1-positive patients with SD and provide a
review of the literature to examine optimal management. RESULTS: Of the 5
patients treated with pallidal DBS, all experienced postoperative resolution of
their dystonic crisis within a range of 1-21 days. Long-term follow-up resulted
in 1 patient returning to preoperative baseline, 3 patients improving from
baseline, and 1 patient making a complete recovery. Of the 28 SD patients
(including our 5 patients) reported in the literature who were treated with DBS
or ablative surgery, 26 experienced cessation of their dystonic crisis with a
return to baseline function and, in most cases, clinical improvement. CONCLUSION:
DBS is an effective therapeutic modality for the treatment of SD. In addition to
the long-term benefits of stimulation, early and aggressive treatment may improve
the overall outcome.
PMID- 27504897
TI - Association of Intestinal Microbiota with Metabolic Markers and Dietary Habits in
Patients with Type 2 Diabetes.
AB - BACKGROUND/AIMS: Evidence suggests that intestinal microbiota, along with factors
such as diet and host genetics, contributes to obesity, metabolic dysfunction and
diabetes. Therefore, we examined the relationship between gut microbiota, blood
metabolic markers, dietary habits and fecal short-chain fatty acids (SCFAs) in
patients with type 2 diabetes mellitus (T2DM). METHODS: Dietary habits, blood and
fecal samples from 59 T2DM patients were recruited, and the association of
intestinal microbiota with metabolic markers and dietary habits was analyzed.
RESULTS: Total energy intake was 1,692 +/- 380 kcal/day. Carbohydrate, fat and
protein intakes were 57.5 +/- 5.2, 23.2 +/- 5.3 and 13.2 +/- 2.2%, respectively.
Dietary habits - high carbohydrate, fat, and protein intake - were associated
with increased counts of Clostridium clusters IV and XI and decreased counts of
Bifidobacterium spp., order Lactobacillales and Clostridium cluster IV. Protein
intake was negatively correlated with fecal acetate and total SCFAs. Total SCFAs,
propionate and acetate were negatively correlated with blood insulin levels and
the homeostasis model of insulin resistance. CONCLUSION: Diets low in protein and
carbohydrates favor a healthy gut microbiome and improve glucose tolerance in
T2DM patients, although further elucidation of the role of the gut microbiome
could lead to better therapies and prophylaxes.
PMID- 27504899
TI - The development of peer reflective supervision amongst nurse educator colleagues:
An action research project.
AB - This action research study developed the use of peer reflective supervision (PRS)
amongst eight nurse educators contributing to an undergraduate Adult Nursing
programme at a UK University. During the academic year (2013-14), nurse educator
co-researchers met for an introductory workshop and then met regularly in pairs
to facilitate each other's reflection. This provided an opportunity for nurse
educators to reflect on identified issues linked to their role with a
facilitative peer. Educators met three additional times in a Reflexive Learning
Group (RLG), to gather data on their use of PRS. Audio-recordings from the RLGs
were transcribed and analysed using Norton's (2009) thematic analysis framework.
Co-researchers iteratively validated the data and an external validation group
critically viewed the evidence. Overall, seven themes were generated from the
three research cycles. These were: PRS as a Valuable Affirming Experience; Time
Issues; Facilitation- Support, Trust and Challenge; Developing a Flexible
'Toolbox'; To Write or Not to Write; Drawing on Literature; and Requirement for
Action. Findings add new evidence regarding use of a flexible toolbox of
resources to develop reflection and offer practical guidance on the development
of PRS. Nurse educators often experienced similar concerns, and a facilitative
supervision structure allowed co-researchers to positively explore these.
Recognition of work pressures and requirement for time and space for reflection
was highlighted, particularly regarding writing, and exploring the literature, to
develop critical analysis of experiences. The importance of action as part of the
reflective process was emphasised. Co-researchers reported positive personal
change as well as the opportunity to highlight issues through their reflection
for further action within the organisation. The study adds constructive evidence
for the use of reflection to explore professional work, make sense of experiences
and develop positive action. It has transferability to a wider international
audience interested in the development of reflection amongst colleagues and the
use of insider research techniques to challenge and develop practice.
PMID- 27504898
TI - Social image concerns promote cooperation more than altruistic punishment.
AB - Human cooperation is enigmatic, as organisms are expected, by evolutionary and
economic theory, to act principally in their own interests. However, cooperation
requires individuals to sacrifice resources for each other's benefit. We
conducted a series of novel experiments in a foraging society where social
institutions make the study of social image and punishment particularly salient.
Participants played simple cooperation games where they could punish non
cooperators, promote a positive social image or do so in combination with one
another. We show that although all these mechanisms raise cooperation above
baseline levels, only when social image alone is at stake do average economic
gains rise significantly above baseline. Punishment, either alone or combined
with social image building, yields lower gains. Individuals' desire to establish
a positive social image thus emerges as a more decisive factor than punishment in
promoting human cooperation.
PMID- 27504900
TI - On the validity of self-report assessment of cognitive abilities: Attentional
control scale associations with cognitive performance, emotional adjustment, and
personality.
AB - Individual differences in attentional control involve the ability to voluntarily
direct, shift, and sustain attention. In studies of the role of attentional
control in emotional adjustment, social relationships, and vulnerability to the
effects of stress, self-report questionnaires are commonly used to measure this
construct. Yet, convincing evidence of the association between self-report scales
and actual cognitive performance has not been demonstrated. Across 2 independent
samples, we examined associations between self-reported attentional control
(Attentional Control Scale; ACS), self-reported emotional adjustment, Five-Factor
Model personality traits (NEO Personality Inventory-Revised) and performance
measures of attentional control. Study 1 examined behavioral performance on the
Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002) and
the Modified Switching Task (MST; Suchy & Kosson, 2006) in a large sample (n =
315) of healthy young adults. Study 2 (n = 78) examined behavioral performance on
standardized neuropsychological tests of attention, including Conner's Continuous
Performance Test-II and subtests from the Wechsler Adult Intelligence Scales,
Third Edition (WAIS-III; Psychological Corporation, 1997) and Delis-Kaplan
Executive Function System (D-KEFS; Delis, Kaplan, & Kramer, 2001). Results
indicated that the ACS was largely unrelated to behavioral performance measures
of attentional control but was significantly associated with emotional
adjustment, neuroticism, and conscientiousness. These findings suggest that
although self-reported attentional control may be a useful construct, researchers
using the ACS should exercise caution in interpreting it as a proxy for actual
cognitive ability or performance. (PsycINFO Database Record
PMID- 27504901
TI - The development and validation of attention constructs from the First Year
Inventory.
AB - Individual differences in early attention are associated with later social,
cognitive, and emotional development, and attentional deficits in the first year
are associated with risk for developmental disorders such as Autism Spectrum
Disorder (ASD). The First Year Inventory (FYI; Baranek, Watson, Crais, & Reznick,
2003) was developed to identify 12-month-olds at risk for an ASD diagnosis. The
current study identifies FYI items that reflect aspects of early attention that
might predict future typical and atypical social, cognitive, and emotional
development. Using a series of theoretical and statistical methods, we developed
3 attention-based constructs from the FYI: Responding to Social Attention (RSA),
Initiating Social Attention (ISA), and Nonsocial Sensory Attention (NSA). A
database with completed FYIs was analyzed using these constructs to determine the
strength of relations among items. Cronbach's alpha analyses indicated good
internal consistency, and item distribution was further supported using a
confirmatory factor analysis. Data analyses showed statistically significant
relations between the scores on these domains at 12 months and subsequent social
responsiveness scores at 3 years. Analyses demonstrating the statistical and
predictive validity of these 3 FYI attention constructs support their use for
innovative explorations of infant behavioral patterns that can be used to predict
typical and atypical individual trajectories in the development of later social,
cognitive, and emotional skills. (PsycINFO Database Record
PMID- 27504902
TI - Cognitive discrepancy models for specific learning disabilities identification:
Simulations of psychometric limitations.
AB - Few studies have investigated specific learning disabilities (SLD) identification
methods based on the identification of patterns of processing strengths and
weaknesses (PSW). We investigated the reliability of SLD identification decisions
emanating from different achievement test batteries for 1 method to
operationalize the PSW approach: the concordance/discordance model (C/DM; Hale &
Fiorello, 2004). Two studies examined the level of agreement for SLD
identification decisions between 2 different simulated, highly correlated
achievement test batteries. Study 1 simulated achievement and cognitive data
across a wide range of potential latent correlations between an achievement
deficit, a cognitive strength and a cognitive weakness. Latent correlations
permitted simulation of case-level data at specified reliabilities for cognitive
abilities and 2 achievement observations. C/DM criteria were applied and
resulting SLD classifications from the 2 achievement test batteries were compared
for agreement. Overall agreement and negative agreement were high, but positive
agreement was low (0.33-0.59) across all conditions. Study 2 isolated the effects
of reduced test reliability on agreement for SLD identification decisions
resulting from different test batteries. Reductions in reliability of the 2
achievement tests resulted in average decreases in positive agreement of 0.13.
Conversely, reductions in reliability of cognitive measures resulted in small
average increases in positive agreement (0.0-0.06). Findings from both studies
are consistent with prior research demonstrating the inherent instability of
classifications based on C/DM criteria. Within complex ipsative SLD
identification models like the C/DM, small variations in test selection can have
deleterious effects on classification reliability. (PsycINFO Database Record
PMID- 27504903
TI - Can the Frost Multidimensional Perfectionism Scale assess perfeccionismo?
AB - Although culture-based measurement bias threatens the validity of intergroup
comparison research, measurement invariance is often assumed rather than
demonstrated by researchers who draw conclusions about cross-cultural
similarities or differences. The current article investigates the cross-cultural
invariance of a popular measure of perfectionism, the Frost Multidimensional
Perfectionism Scale (F-MPS; Frost, Marten, Lahart, & Rosenblate, 1990) for a
Hispanic/Latina sample. Perfectionism, which encompasses high goal setting and
sensitivity to critical evaluation, is a transdiagnostic risk factor for
internalizing psychopathology that especially warrants focus among groups
burdened by mental health disparities. Multiple samples were used in a series of
analyses to construct a baseline first-order measurement model and test for cross
group equivalence. For model development, confirmatory factor analyses (CFAs)
were used with 320 female participants (Mage = 19.61 years) who identified
primarily (n = 301) as European/European American. Measurement invariance testing
was conducted with multigroup CFAs using another sample of female adults (n =
574; Mage = 21.21 years), identifying either as European/European American (n =
217) or Hispanic/Latina/Latin American (n = 357). Evidence was found for
invariance across the revised F-MPS factor structure, pattern of factor loadings,
and factor variances/covariances. Results indicate that predictive relationships
may be compared across these groups, but caution is suggested when interpreting
raw mean score differences due to intercept nonequivalence. Further, second-order
model testing demonstrated support for the bidimensional model of perfectionism
cross-culturally. Future research on perfectionism within the Latino/a population
is encouraged using this equivalent item set. (PsycINFO Database Record
PMID- 27504904
TI - Resilience in the United States Air Force: Psychometric properties of the Connor
Davidson Resilience Scale (CD-RISC).
AB - Results are presented for the largest study (N = 53,692) ever conducted on the 25
item Connor-Davidson Resilience Scale (CD-RISC), a popular measure of resilience.
We examined the internal consistency of the CD-RISC items and associated mean
resilience levels within a sample of enlisted basic trainees in the United States
Air Force. In addition, the predictive validity of the CD-RISC Total Score was
examined for real-life military outcomes, including attrition from service and
mental health diagnosis. The CD-RISC items demonstrated strong internal
consistency. Item-level examinations of scores revealed that most trainees
reported relatively high resilience. Results indicated that resilience measured
at the beginning of military service is a significant predictor of (a) attrition
from service and (b) obtaining a mental health diagnosis within 6 months of
entry. Implications and future directions are discussed. (PsycINFO Database
Record
PMID- 27504905
TI - Evaluation of the Response Bias Scale and Improbable Failure Scale in assessing
feigned cognitive impairment.
AB - The present study evaluated the Response Bias scale (RBS), a symptom validity
test embedded within the Minnesota Multiphasic Personality Inventory (MMPI)-2
Restructured Form (MMPI-2-RF) that assesses for feigned neurocognitive
complaints, in a sample of pretrial incompetent to stand trial (IST) criminal
defendants. Additionally, we examined the Improbable Failure (IF) scale, a
performance validity test embedded within the Structured Interview of Reported
Symptoms, Second Edition (SIRS-2), which similarly assesses for feigned cognitive
impairment (FCI). Results indicated that both the RBS (area under the curve [AUC]
= .76) and IF scale (AUC = .72) achieved moderate classification accuracy using
the Test of Memory Malingering (TOMM) as the criterion. Further, the RBS and IF
scale appeared to be most useful for screening out those defendants who presented
as genuine (specificity = 99% and 88%, respectively), and less effective at
classifying those defendants suspected of feigning according to the TOMM
(sensitivity = 29% and 46%, respectively). In order to identify a significant
proportion of IST defendants who may be feigning impairment, considerably lower
cutoff scores than those recommended in each measure's manual were evaluated. An
RBS T score of 63 (sensitivity = 86%; specificity = 37%), and IF scale raw score
of 2 (sensitivity = 80%; specificity = 43%), was required to achieve >=80%
sensitivity; these alternate cutoff scores may therefore be useful when screening
inpatient forensic psychiatric IST defendants. Further, the 2 scales effectively
predicted TOMM classification in combination, although only the RBS significantly
contributed to the model. Implications for the assessment of FCI in forensic
psychiatric settings are discussed. (PsycINFO Database Record
PMID- 27504906
TI - Use of universal screening scores to predict distal academic and behavioral
outcomes: A multilevel approach.
AB - Initial research suggests screening for behavioral and emotional risk has been
found to predict important behavioral and academic outcomes. The current study
seeks to investigate the predictive validity of a novel screening measure, the
Social, Academic, and Emotional Behavior Risk Screener-Teacher Rating Scale
(SAEBRS-TRS). Although the SAEBRS-TRS has demonstrated initial evidence of strong
psychometric properties (including reliability and validity), less is known about
the SAEBRS-TRS's prediction of important student academic and behavioral
outcomes. Hierarchical linear modeling (HLM) was employed due to the nested
nature of the data of screening school-age children within classrooms. Results
revealed that fall behavior screening data significantly and positively predicted
spring reading scores, office disciplinary referrals, and student absences. Very
little variance in the current model was due to differences between classrooms.
Results suggest screening may be an important tool for school personnel seeking
to use preventative methods for addressing student barriers to learning.
(PsycINFO Database Record
PMID- 27504907
TI - Evaluating juvenile detainees' Miranda misconceptions: The discriminant validity
of the Juvenile Miranda Quiz.
AB - Most juvenile arrestees in custodial settings waive their Miranda rights almost
immediately, and many then provide incriminating statements, if not outright
confessions. Forensic practitioners are then asked to provide retrospective
determinations regarding whether these waivers were effectuated knowingly,
voluntarily, and intelligently. At present, the forensic assessment instrument
for juvenile Miranda issues consists of the Miranda Rights Comprehension
Instruments (MRCI)-which as its name implies-focuses mostly on Miranda
comprehension with a de-emphasis of Miranda reasoning. In partially addressing
this gap, the current study investigated the clinical utility of the Juvenile
Miranda Quiz (JMQ) for evaluating key Miranda misconceptions, a critically
important component of Miranda reasoning. Using data from 201 juvenile detainees,
we evaluated the JMQ's discriminability with regards to cognitive variables and
MRCI scales. Many moderate effect sizes in the predicted direction were found for
the JMQ Primary Total and Juvenile Total scores. Finally, these detainees were
tested using a mock crime scenario with a representative Miranda warning plus a
brief interrogation to evaluate whether they would waive their rights, and if so,
whether they would confess. Using Miranda measures to predict problematic
outcomes (i.e., impaired waivers followed by confessions), the JMQ Juvenile Total
proved the most successful. These findings are discussed within the context of
the "intelligent" prong of Miranda waivers. (PsycINFO Database Record
PMID- 27504908
TI - Mechanism and Kinetics of Heterogeneous Reactions of Unsaturated Organic Acids on
alpha-Al2 O3 and CaCO3.
AB - Heterogeneous reactions have a vital role in the atmosphere due to their
significant effects on the evolution of atmospheric aerosols, which in turn
contribute to air pollution. However, the mechanism and kinetics of these
processes involving unsaturated organic acids, important types of volatile
organic compounds, are still unclear. In this work, the heterogeneous uptake of
two representative atmospheric unsaturated organic acids (acrylic acid and
methacrylic acid) on mineral aerosols including alpha-Al2 O3 and CaCO3 are
investigated using a Knudsen cell reactor and an in situ diffuse reflectance
infrared Fourier transform spectrometry (DRIFTS) reactor. The corresponding
reaction pathways are proposed from the DRIFTS analysis. In addition, the initial
uptake coefficients of unsaturated organic acids and their heterogeneous fate are
obtained for the first time. Our results suggest that heterogeneous reactions on
alpha-Al2 O3 and CaCO3 can be important sinks for acrylic acid and methacrylic
acid, as well as possible contributors to the organic coating found on
atmospheric aerosols, especially in high-pollution events.
PMID- 27504909
TI - Enhancer decommissioning by Snail1-induced competitive displacement of TCF7L2 and
down-regulation of transcriptional activators results in EPHB2 silencing.
AB - Transcriptional silencing is a major cause for the inactivation of tumor
suppressor genes, however, the underlying mechanisms are only poorly understood.
The EPHB2 gene encodes a receptor tyrosine kinase that controls epithelial cell
migration and allocation in intestinal crypts. Through its ability to restrict
cell spreading, EPHB2 functions as a tumor suppressor in colorectal cancer whose
expression is frequently lost as tumors progress to the carcinoma stage.
Previously we reported that EPHB2 expression depends on a transcriptional
enhancer whose activity is diminished in EPHB2 non-expressing cells. Here we
investigated the mechanisms that lead to EPHB2 enhancer inactivation. We show
that expression of EPHB2 and SNAIL1 - an inducer of epithelial-mesenchymal
transition (EMT) - is anti-correlated in colorectal cancer cell lines and tumors.
In a cellular model of Snail1-induced EMT, we observe that features of active
chromatin at the EPHB2 enhancer are diminished upon expression of murine Snail1.
We identify the transcription factors FOXA1, MYB, CDX2 and TCF7L2 as EPHB2
enhancer factors and demonstrate that Snail1 indirectly inactivates the EPHB2
enhancer by downregulation of FOXA1 and MYB. In addition, Snail1 induces the
expression of Lymphoid enhancer factor 1 (LEF1) which competitively displaces
TCF7L2 from the EPHB2 enhancer. In contrast to TCF7L2, however, LEF1 appears to
repress the EPHB2 enhancer. Our findings underscore the importance of
transcriptional enhancers for gene regulation under physiological and
pathological conditions and show that SNAIL1 employs a combinatorial mechanism to
inactivate the EPHB2 enhancer based on activator deprivation and competitive
displacement of transcription factors.
PMID- 27504910
TI - Fizzy Extraction of Volatile and Semivolatile Compounds into the Gas Phase.
AB - Extraction of volatile and semivolatile compounds from liquid matrixes with high
yields, and transferring the extracts to detectors in real time, is challenging.
Common extraction procedures involve heating the samples to release the analytes
to the gas phase and, in some cases, trapping the gas-phase analytes into
sorbents or containers. Here, we propose a new method for fast extraction of
volatile and semivolatile compounds from liquid matrixes. This method involves
dissolution of a carrier gas in the liquid sample by applying a moderate
overpressure (~150 kPa) and stirring the sample. An abrupt decompression of the
extraction chamber leads to effervescence. In this step, many bubbles are
instantly formed in the sample matrix. The dissolved carrier gas as well as
dissolved volatiles are liberated into the headspace of the extraction chamber
within a short period of time (few seconds). The gaseous effluent of the
extraction chamber is immediately transferred to the online detector; in this
case, an atmospheric pressure chemical ionization interface of a triple
quadrupole mass spectrometer. The fast release of the gas-phase extract gives
rise to a high signal recorded by the detector; several times higher than the
signal recorded during direct infusion of headspace vapors without fizzy
extraction. This feature provides the means to detect and quantify analytes
present in solutions in a short period of time. Here we show that fizzy
extraction is suitable for analysis of volatile/semivolatile compounds present in
various samples, including those containing complex matrixes.
PMID- 27504911
TI - Metformin use and risk of lactic acidosis in people with diabetes with and
without renal impairment: a cohort study in Denmark and the UK.
AB - AIMS: To assess risk of lactic acidosis among metformin users compared with other
glucose-lowering agent users, according to renal function. METHODS: Using routine
registries and databases, we conducted a cohort study. Of 43 580 metformin and 37
788 other glucose-lowering agent users in northern Denmark and 102 688 metformin
and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we
identified lactic acidosis using diagnostic codes. We calculated the incidence
rates of lactic acidosis in metformin and other glucose-lowering agent users
overall and according to baseline estimated GFR (eGFR) levels. RESULTS: In
Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and
1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other
glucose-lowering agent use, respectively. In the UK, the corresponding lactic
acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per
100 000 person-years of metformin use and of other glucose-lowering agent use.
The incidence rates increased with decreasing baseline eGFR in both countries. Of
the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the
UK experienced a decline in renal function in the year before the diagnosis.
CONCLUSIONS: Risk of lactic acidosis was higher in metformin users than in other
glucose-lowering agent users, and increased with decreasing eGFR, although this
could be attributable to surveillance bias; however, diagnosed lactic acidosis
was rare and can occur regardless of renal function.
PMID- 27504912
TI - Determinants of Salivary Cotinine among Smokeless Tobacco Users: A Cross
Sectional Survey in Bangladesh.
AB - INTRODUCTION: More than 80% of all smokeless tobacco (ST) products in the world
are consumed in South Asia; yet little is known about their consumption
behaviour, addictiveness, and toxic properties. This paper, for the first time,
describes associations between salivary cotinine concentrations among ST users in
Bangladesh and their socio-demographic characteristics and tobacco use
behaviours. METHODS: In a survey of ST users in Dhaka, Bangladesh, we purposively
recruited 200 adults who were non-smokers but consumed ST on a regular basis. In
person interviews were conducted to obtain information about socio-demographic
and ST use behaviours, and saliva samples were collected to measure cotinine
concentration. Simple and multiple linear regression analyses were conducted to
test associations between the log transformed salivary cotinine concentration and
other study variables. RESULTS: The geometric mean of cotinine concentration
among ST users was 380ng/ml (GSD:2). Total duration of daily ST use in months had
a statistically significant association with cotinine concentration. Other ST use
characteristics including type and quantity of ST use, swallowing of tobacco
juice, urges and strength of urges and attempts to cut down on tobacco use were
not found to be associated with cotinine concentration in a multivariable model.
CONCLUSION: This is the first report from Bangladesh studying cotinine
concentration among ST users and it points towards high levels of addiction. This
warrants effective tobacco control policies to help ST cessation and prevention.
PMID- 27504913
TI - Effectiveness of abdominal shields in chest radiography: a Monte Carlo
evaluation.
AB - OBJECTIVE: The aims of this study were to assess the effectiveness of abdominal
shields in reducing the dose to shielded organs during posteroanterior (PA) chest
radiographic examinations, to evaluate the various factors contributing to the
dose under the shield and to address the concern that internal scatter from the
shield may lead to a dose increase to shielded organs. METHODS: Monte Carlo
simulations of radiographic exposures to a soft-tissue "patient" phantom of 80 *
34 * 24 cm were performed at the peak X-ray tube voltage of 100 kV. The abdominal
shield was simulated as 0.5-mm lead with/without a 0.2-mm-thick plastic film
cover. The shield-to-phantom spacing varied from 0 to 40 cm. RESULTS: The dose to
the phantom at different phantom depths and distances from the X-ray field edge
was recorded. At the level of the uterus and ovaries (approximately 8-cm deep and
15 cm from the field of view), the dose reduction was approximately 0.035 uGy or
4%. A small dose increase (maximum: 0.4 uGy) to the phantom surface layer was
also observed. CONCLUSION: In general, there was a small dose reduction in
regions protected by the shield. However, the overall risk benefit to a patient
would be negligible. ADVANCES IN KNOWLEDGE: Abdominal shields used during PA
chest radiography provide a small dose reduction to organs at depth by removing
the primary X-ray beam photons that are scattered in air, while giving a small
increase in skin dose due to X-rays scattered from the abdominal shield internal
surface.
PMID- 27504914
TI - Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe
plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double
blind study.
AB - BACKGROUND: This phase 3 trial is the first to evaluate the efficacy and safety
of treatment with the systemic TNF-alpha inhibitor, adalimumab, for Chinese
patients with moderate-to-severe plaque psoriasis. METHODS: In the 12-week,
double-blind, placebo-controlled Period A, patients were randomized 4 : 1 to
receive adalimumab 40 mg every-other-week (following a single 80 mg dose), or
placebo every-other-week. In the subsequent 12-week, open-label, Period B, all
patients received adalimumab 40 mg every-other-week starting at week 13,
following a single, blinded dose at week 12 of adalimumab 80 mg or matching
placebo (for patients receiving placebo or adalimumab in Period A respectively).
In Period A, efficacy was analysed for all randomized patients and safety for all
patients receiving >=1 dose of the study drug. RESULTS: For the 425 patients in
this study (87 placebo; 338 adalimumab), a higher percentage randomized to
adalimumab achieved the primary endpoint of >=75% improvement from baseline in
PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8%
(263/338; P < 0.001). Physician's Global Assessment of clear to minimal was
achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P <
0.001). For patients who received adalimumab at any time during the study (All
adalimumab Population), treatment-emergent adverse events (AEs) were reported by
63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were
reported by 3.5% of the All-adalimumab Population, and serious infectious AEs by
1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients
each]. There was one death (chronic heart failure). CONCLUSION: In these Chinese
patients with moderate-to-severe psoriasis, a significantly greater percentage
treated with adalimumab compared with placebo achieved efficacy endpoints at week
12 and efficacy was sustained to week 24. Safety results were consistent with the
known adalimumab safety profile; no new safety signals were identified in the 24
weeks of treatment.
PMID- 27504915
TI - Psychometric Properties of the Problematic Internet Use Questionnaire Short-Form
(PIUQ-SF-6) in a Nationally Representative Sample of Adolescents.
AB - Despite the large number of measurement tools developed to assess problematic
Internet use, numerous studies use measures with only modest investigation into
their psychometric properties. The goal of the present study was to validate the
short (6-item) version of the Problematic Internet Use Questionnaire (PIUQ) on a
nationally representative adolescent sample (n = 5,005; mean age 16.4 years, SD =
0.87) and to determine a statistically established cut-off value. Data were
collected within the framework of the European School Survey Project on Alcohol
and Other Drugs project. Results showed an acceptable fit of the original three
factor structure to the data. In addition, a MIMIC model was carried out to
justify the need for three distinct factors. The sample was divided into users at
risk of problematic Internet use and those with no-risk using a latent profile
analysis. Two latent classes were obtained with 14.4% of adolescents belonging to
the at-risk group. Concurrent and convergent validity were tested by comparing
the two groups across a number of variables (i.e., time spent online, academic
achievement, self-esteem, depressive symptoms, and preferred online activities).
Using the at-risk latent profile analysis class as the gold standard, a cut-off
value of 15 (out of 30) was suggested based on sensitivity and specificity
analyses. In conclusion, the brief version of the (6-item) PIUQ also appears to
be an appropriate measure to differentiate between Internet users at risk of
developing problematic Internet use and those not at risk. Furthermore, due to
its brevity, the shortened PIUQ is advantageous to utilize within large-scale
surveys assessing many different behaviors and/or constructs by reducing the
overall number of survey questions, and as a consequence, likely increasing
completion rates.
PMID- 27504916
TI - Cultivating the social-emotional imagination in gifted education: insights from
educational neuroscience.
AB - Evidence from education, psychology, and neuroscience suggests that investing in
the development of the social-emotional imagination is essential to cultivating
giftedness in adolescents. Nurturing these capacities may be especially effective
for promoting giftedness in students who are likely to lose interest and ambition
over time. Giftedness is frequently equated with high general intelligence as
measured by IQ tests, but this narrow conceptualization does not adequately
capture students' abilities to utilize their talents strategically to fully
realize their future possible selves. The brain's default mode network is thought
to play an important role in supporting imaginative thinking about the self and
others across time. Because this network's functioning is temporarily attenuated
when individuals engage in task- and action-oriented focus (mindsets thought to
engage the brain's executive attention network), we suggest that consistently
focusing students on tasks requiring immediate action could undermine long-term
cultivation of giftedness. We argue that giftedness-especially in science,
technology, engineering, and mathematics (STEM)-can be cultivated by encouraging
adolescents' intellectual curiosity and supporting their ability to connect
schoolwork to a larger purpose. Improving STEM and gifted education may depend
upon a shift from knowledge transmission and regimented evaluation to creative
exploration, intentional reflectiveness, and mindful switching between task focus
and imagining.
PMID- 27504917
TI - Intra-Arterial Chemotherapy as Primary Therapy for Retinoblastoma in Infants Less
than 3 Months of Age: A Series of 10 Case-Studies.
AB - PURPOSE: Retinoblastoma is the most common primary malignant intra-ocular tumor
in children. Although intra-arterial chemotherapy (IAC) by selectively infusing
chemotherapy through the ophthalmic artery has become an essential technique in
the treatment of advanced intra-ocular retinoblastoma in children, the outcome of
IAC as primary therapy for infants less than 3 months of age remains unknown. In
this retrospective study, we reviewed the outcome of IAC as primary therapy for
retinoblastoma in infants less than 3 months of age. METHODS: We retrospectively
reviewed ten retinoblastoma patients attending our center from January 2009 to
September 2015 and beginning primary IAC before the age of 3 months. The patient
characteristics, overall outcomes and therapy-related complications were
assessed. RESULTS: The mean patient age at the first IAC treatment was 10.4 weeks
(range 4.9-12.9 weeks). These eyes were classified according to the International
Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 2), C (n = 0),
D (n = 9), or E (n = 2). A total of 28 catheterizations were performed, and the
procedure was stopped in one patient because of internal carotid artery spasm.
Each eye received a mean of 2.6 cycles of IAC (range 2-4 cycles). After IAC with
a mean follow-up of 28.3 months (range 9-65 months), tumor regression was
observed in 12 of 13 eyes. One eye was enucleated due to tumor progression. All
patients are alive and no patient has developed metastatic disease or other
malignancies. CONCLUSIONS: Our experience suggests IAC as primary therapy is a
feasible and promising treatment for retinoblastoma in infants less than 3 months
of age.
PMID- 27504918
TI - Effectiveness and cost-effectiveness of pessary treatment compared with pelvic
floor muscle training in older women with pelvic organ prolapse: 2-year follow-up
of a randomized controlled trial in primary care.
AB - OBJECTIVE: We investigated the effectiveness and cost-effectiveness of pessary
treatment compared with pelvic floor muscle training (PFMT) in women with pelvic
organ prolapse over a 2-year period. METHODS: Randomized controlled trial with
women (>=55 y) with symptomatic pelvic organ prolapse, identified by screening.
Participants were recruited from 20 primary care practices (October 2009-December
2012). Primary outcome was the difference in change of pelvic floor symptoms
(PFDI-20 score) between groups over 24 months. Secondary outcomes included
prolapse, urinary, and anorectal symptoms; quality of life; costs; sexual
functioning; prolapse stage; pelvic floor muscle function; and participants'
perceived symptom improvement. RESULTS: There was a nonsignificant difference in
the primary outcome between pessary treatment (n = 82) and PFMT (n = 80) with a
mean difference of -3.7 points (95% CI, -12.8 to 5.3; P = 0.42) in favor of
pessary treatment. A significantly greater improvement in the prolapse symptom
score was, however, seen with pessary treatment (mean difference -3.2 points [95%
CI, -6.3 to -0.0; P = 0.05]). Direct medical costs over the 2-year study were
$309 and $437 per person for pessary treatment and PFMT, respectively.
CONCLUSIONS: In older women with symptomatic prolapse, there was no significant
difference between pessary treatment and PFMT in reducing pelvic floor symptoms,
but specific prolapse-related symptoms did improve more with pessary treatment.
Pessary treatment was preferable in the cost-effectiveness analysis. When
counseling women for prolapse treatment it should, however, be taken into account
that pessary fitting fails in a considerable portion of women and that pessary
treatment was associated with more side effects compared with PFMT.
PMID- 27504919
TI - Use of systemic hormone therapy in BRCA mutation carriers.
AB - As more women are being counseled and tested, clinicians increasingly encounter
women with identified BRCA1 and BRCA2 gene mutations. Existing, albeit limited,
data indicate that risks of breast cancer are not increased with use of systemic
hormone therapy by menopausal BRCA mutation carriers with intact breasts. Young
mutation carriers with or without intact breasts should not defer or avoid risk
reducing (and lifesaving) bilateral salpingo-oophorectomy because of concerns
that subsequent use of systemic hormone therapy will elevate breast cancer risk.
PMID- 27504920
TI - Ultraviolet Light Catalyzed Gelation of 3-Methacryloxypropyltrimethoxysilane via
Altered Silicate Spatial Structure.
AB - The gelation of 3-methacryloxypropyltrimethoxysilane (MAPTMS) is much more
difficult to achieve in conventional conditions. This article describes a novel
and concise approach to acquire transparent and firm hybrid gel material by one
step promptly without photoinitiator or other tetraalkoxysilane. MAPTMS was
hydrolyzed in acidified aqueous solution, which became homogeneous sol in 3 min,
and then the sol was irradiated with UV light for a few minutes to form gel. The
experimental results indicated that MAPTMS sol gelled in the presence of UV
irradiation was mainly attributed to altering Si-O-Si skeleton structure through
hydroxyl radicals, and the gelation originated from the hydrolytic
polycondensation of MAPTMS rather than the polymerization of methacryloxy
substituent groups. The hydroxyl radicals could break the Si-O-Si ring structure
to form cross-linker like species, and these cross-linkers chemically joined
linear chains together to form the gel network. This investigation offers not
only the photoinduced gelation strategy for MAPTMS sol but also the new insight
into the effect of UV-irradiation on the sol-gel process of
organotrialkoxysilanes.
PMID- 27504921
TI - The influence of gender on suicidal ideation following military sexual trauma
among Veterans in the Veterans Health Administration.
AB - No studies have examined whether military sexual trauma, as measured and defined
within the Veterans Health Administration (VHA), is associated with suicidal
ideation among Veterans in VHA care, when taking prior suicide attempts into
account. Research regarding the role of gender in this association is also
limited. The present study examined: (1) whether military sexual trauma was
associated with the presence of past-week suicidal ideation among 354 Veterans in
VHA (310 men, 44 women); (2) whether gender moderated the association between
military sexual trauma and suicidal ideation. Information regarding military
sexual trauma, suicidal ideation, suicide attempt, and psychiatric diagnoses was
obtained from self-report instruments and medical records. Adjusting for age,
gender, combat, posttraumatic stress disorder, depressive disorders, negative
affect, and lifetime suicide attempt, Veterans with military sexual trauma were
significantly more likely to report suicidal ideation, compared to Veterans
without military sexual trauma. Furthermore, the association between military
sexual trauma and suicidal ideation was stronger for men compared to women. These
results contribute to a growing literature identifying military sexual trauma as
a risk factor for suicidal thoughts and behaviors among Veterans in VHA care and
emphasize the importance of screening for suicidal ideation among survivors of
military sexual trauma.
PMID- 27504922
TI - Accurate Cytotoxicity and Proliferation Determination: Advantages of a High
Throughput Phenotypic Approach Over ATP Luminescence Assays.
AB - Cell viability and proliferation assays are a fundamental tool in the drug
discovery process and are used to evaluate both the antiproliferative potency and
toxicity of compounds. Some lead discovery groups generate cell viability data
for up to two million compounds per screen, so any method used to assess these
parameters needs to deliver not only on data quality but also on throughput and
assay cost per well. Most methods used to determine cell viability cannot deliver
on all three of these requirements, so compromises have to be made. Here we show
the development and implementation of a cost-effective, no-wash phenotypic assay
to simultaneously report the number of cells, percentage of live cells, and cell
cycle phase distribution as markers of proliferation and viability. We
demonstrate that this assay can be applied to high-density plate formats and be
imaged and analyzed in 8 min per plate on a laser scanning imaging cytometer. By
comparing the drug-responses of several well-characterized anticancer drugs on
HeLa cells, we highlight the key differences between the phenotypic assay and a
commercial ATP luminescence detection system.
PMID- 27504923
TI - Brief Opioid Overdose Knowledge (BOOK): A Questionnaire to Assess Overdose
Knowledge in Individuals Who Use Illicit or Prescribed Opioids.
AB - BACKGROUND: Opioid overdose is a public health crisis. This study describes
efforts to develop and validate the Brief Opioid Overdose Knowledge (BOOK)
questionnaire to assess patient knowledge gaps related to opioid overdose risks.
METHODS: Two samples of illicit opioid users and a third sample of patients
receiving an opioid for the treatment of chronic pain (total N = 848) completed
self-report items pertaining to opioid overdose risks. RESULTS: A 3-factor scale
was established, representing Opioid Knowledge (4 items), Opioid Overdose
Knowledge (4 items), and Opioid Overdose Response Knowledge (4 items). The scale
had strong internal and face validity. Patients with chronic pain performed worse
than illicit drug users in almost all items assessed, highlighting the need to
increase knowledge of opioid overdose risk to this population. CONCLUSIONS: This
study sought to develop a brief, internally valid method for quickly assessing
deficits in opioid overdose risk areas within users of illicit and prescribed
opioids, to provide an efficient metric for assessing and comparing educational
interventions, facilitate conversations between physicians and patients about
overdose risks, and help formally identify knowledge deficits in other patient
populations.
PMID- 27504924
TI - Substance Use as a Risk Factor for Sleep Problems Among Adolescents Presenting to
the Emergency Department.
AB - OBJECTIVES: To determine correlates of sleep problems among adolescents.
Specifically, to assess the relative strength of associations between sleep
problems and dating victimization, reasons for emergency department (ED) visit,
depression, unhealthy alcohol use, and other drug use (marijuana, nonmedical use
of prescription opioids, stimulants, and tranquilizers). METHODS: A total of 1852
adolescents aged 14 to 20 years presenting for care to the University of Michigan
Emergency Department, Ann Arbor, Michigan, during 2011-2012, self-administered a
computerized health survey. Sleep problems were identified if any of the 4 items
on the Sleep Problems Questionnaire were rated by a patient as greater than 3 on
a 0 to 5 scale. Adolescents who were too sick to be screened in the ED were
eligible to participate in the study during their inpatient stay. Exclusion
criteria for baseline included insufficient cognitive orientation precluding
informed consent, not having parent/guardian present if younger than 18 years,
medical severity precluding participation, active suicidal/homicidal ideation,
non-English-speaking, deaf/visually impaired, or already participated in this
study on a prior visit. RESULTS: 23.5% of adolescents reported clinically
significant sleep problems. Female gender, depression, dating victimization,
tobacco use, nonmedical use of prescription medication, and an ED visit for
medical reasons were each associated with sleep problems among adolescents, even
while controlling for age, other types of drug use, receiving public assistance,
and dropping out of school. CONCLUSIONS: These exploratory findings indicate that
ED-based screening and brief intervention approaches addressing substance use
and/or dating victimization may need to account for previously undiagnosed sleep
problems.
PMID- 27504925
TI - Immediate Versus Delayed Computerized Brief Intervention for Illicit Drug Misuse.
AB - OBJECTIVE: Computerized brief interventions are a promising approach for
integrating substance use interventions into primary care settings. We sought to
examine the effectiveness of a computerized brief intervention for illicit drug
misuse, which prior research showed performed no worse than a traditional in
person brief intervention. METHODS: Community health center patients were
screened for eligibility using the World Health Organization Alcohol, Smoking,
and Substance Involvement Screening Test (ASSIST). Participants were adult
patients (aged 18-62 years; 53% female) with moderate-risk illicit drug use (N =
80), randomized to receive the computerized brief intervention either immediately
or at their 3-month follow-up. Assessments were conducted at baseline, 3, and 6
month follow-up, and included the ASSIST and drug hair testing. RESULTS: Most
participants in the sample (90%) reported moderate-risk marijuana use. Although
the sample as a whole reported significant decreases in ASSIST Global Drug Risk
scores and ASSIST marijuana-specific scores, no significant differences were
detected between "immediate" and "delayed" conditions on either of these
measures. Likewise, no significant differences were detected between conditions
in drug-positive hair test results at either follow-up. CONCLUSIONS: This study
did not find differences between immediate versus delayed computerized brief
intervention in reducing drug use or associated risks, suggesting potential
regression to the mean or reactivity to the consent, screening, or assessment
process. The findings are discussed in light of the study's limitations and
directions for future research.
PMID- 27504926
TI - The Availability of Ancillary Counseling in the Practices of Physicians
Prescribing Buprenorphine.
AB - OBJECTIVE: We set out to examine physicians' perceptions of the provision of
ancillary services for opioid dependent patients receiving buprenorphine.
METHODS: An e-mail invitation describing the study was sent out by the American
Society of Addiction Medicine to its membership (approximately 3700 physicians)
and other entities (for a total of approximately 7000 e-mail addresses). E-mail
recipients were invited to participate in a research study funded by the National
Institutes on Drug Abuse involving completion of an online survey; 346 physicians
completed the survey. RESULTS: The majority of the 346 respondents were internal
or family medicine (37%), or addiction medicine providers (30%), who were
practicing in urban (57%) or suburban settings (27%). Most respondents reported
either offering (66%) or referring patients for ancillary counseling (31%).
Interventions that were most frequently offered or referrals provided were
individual counseling (51%) and self-help groups (63%), respectively. Counseling
availability differed significantly by provider specialization for any,
individual, group, family or couples, and self-help groups. CONCLUSIONS:
Generally, respondents reported compliance with ancillary counseling requirements
for buprenorphine treatment of opioid use disorder. In addition to examining the
efficacy of a variety of ancillary counseling services for patients receiving
opioid agonist treatment, further research should examine physicians' attitudes
toward the role of such counseling in buprenorphine treatment. Although the study
sample was relatively large, the generalizability of the findings is unclear,
suggesting that further investigation of the availability of ancillary counseling
in buprenorphine treatment among a larger nationally representative sample of
providers may be warranted.
PMID- 27504927
TI - Bupropion "Abuse" Reported to US Poison Centers.
AB - OBJECTIVES: Bupropion use to obtain nonmedical psychoactive effects has been
reported. The objective was to determine the prevalence, characteristics,
clinical effects, and outcomes of bupropion "abuse." METHODS: A 14-year
retrospective review was conducted of single substance bupropion cases with
"intentional abuse" as the coded reason for exposure in individuals 13 and older
reported to the National Poison Data System. Data were evaluated for prevalence,
demographics, clinical effect, route, final management site, and coded outcome.
RESULTS: There were 975 bupropion abuse cases, which accounted for 3.3% of single
substance bupropion cases reported to US poison centers. The prevalence of abuse
increased by 75%, from 2000 to 2012, declining slightly in 2013. The majority of
cases were 13 to 29 years old (67.4%). The most frequent clinical effects were
tachycardia (57.0%), seizures (33.5%), agitation/irritable (20.2%),
hallucinations/delusions (14.0%), and tremor (13.1%). Most exposures were
ingestions (745) followed by insufflation (166), parenteral (17), and
other/unknown (17); 30 cases involved 2 routes. Seizure frequency was not
significantly different between routes (P = 0.783) or exposure chronicity (P =
0.264). Final management sites were predominantly emergency department (36.9%)
and admission to critical care unit (27.3%) or noncritical care unit (20.1%).
Outcomes were major (11.4%), moderate (48.2%), minor (24.5%), and no effect
(15.5%). There were 4 deaths. CONCLUSIONS: Most bupropion abuse occurs in
adolescents and young adults. Tachycardia and seizures are common indicating the
potential for serious effects. Seizures occur regardless of route. Providers
should be aware of risk of bupropion abuse.
PMID- 27504928
TI - Sex Differences in the Association Between Internalizing Symptoms and Craving in
Methamphetamine Users.
AB - OBJECTIVES: Methamphetamine (MA) users often have substantial psychiatric
comorbidities, with nearly a third reporting lifetime mood disorders and over a
quarter reporting lifetime anxiety disorders. Female MA users are more likely to
endorse depression and anxiety symptoms compared with men. Craving has been
related to mood/anxiety symptoms in MA users. To extend the literature on sex
differences in MA use disorder, the present study examines the role of sex as a
moderator of the relationship between mood/anxiety symptoms and MA craving.
METHODS: Participants (N = 203) were nontreatment-seeking, current MA users,
recruited from the Los Angeles community for enrollment in a larger
pharmacotherapy trial. At the assessment visit, participants completed multiple
measures including the Methamphetamine Urge Questionnaire, the Beck Depression
Inventory, and the Beck Anxiety Inventory. RESULTS: The relationship between
depression symptomatology and MA craving was moderated by sex (F = 6.18, P =
0.01), such that the relationship was positive and significant for men (P <
0.001), but was not significant for women. Similarly, sex significantly moderated
the relationship between anxiety and MA craving (F = 5.99, P = 0.02), such that
the relationship was also positive and significant in men, but not in women (P <
0.001). CONCLUSIONS: These results suggest that men may be more sensitive to the
effects of internalizing symptoms on MA craving than women. Given craving's
propensity to predict relapse, these initial findings indicate the necessity of
treating comorbid psychiatric problems in male MA users, which may in turn assist
in the attenuation of craving.
PMID- 27504929
TI - Poly(colloid)s: "Polymerization" of Poly(l-tyrosine)-silica Composite Particles
through the Photoinduced Cross-Linking of Unmodified Proteins Method.
AB - Photoinduced cross-linking of unmodified proteins, PICUP, was extended to core
shell silica-polypeptide composite particles to produce poly(colloid)s. Silica
particles coated with poly(l-tyrosine), PTYR-SiO2, served as the monomer units.
The PICUP reaction accomplished the formation of dityrosil linkages between the
tyrosine units by illumination of photo-oxidizing ruthenium(II) bipyridyl
catalyst under physiological conditions. The PICUP method was compared with an
enzymatic route intermediated by horseradish peroxidase as catalyst. The PTYR
SiO2 particles feature high PTYR content in the shell, which facilitated the
formation of heavily cross-linked but unstructured aggregates. After magnetic
alignment of superparamagnetic PTYR-SiO2-cobalt composite particles, only the
PICUP approach enabled the preparation of isolated chain-like poly(colloid)s. The
cross-linking products were confirmed by FTIR. The native secondary structure of
poly(l-tyrosine) is preserved in these poly(colloid)s. Because the PICUP reaction
does not require the modification of the polypeptide structure, the cross-linked
PTYR will retain its characteristic functions as a poly(amino acid). The PICUP
method opens the door to a variety of PTYR-based poly(colloid) architectures.
PMID- 27504930
TI - Enzymatic assays for detecting lactose and sucrose in urine to reveal intravenous
drug abuse with emphasis on buprenorphine.
AB - Buprenorphine and methadone are commonly used medications for opioid maintenance
treatment (OMT), using sublingual and oral administration, respectively. Although
beneficial for OMT, these drugs can also be abused by intravenous administration.
In intravenous abuse cases, the adjuvants lactose and sucrose are excreted in
urine without hydrolysis to monosaccharides, since there are no disaccharidases
in the blood. We validated enzymatic methods for the analysis of lactose and
sucrose in urine. The analytical performance of both assays was considered
appropriate for detecting intravenous drug abuse. The principle was proven by
analyzing 93 postmortem (PM) urine samples for lactose, following comprehensive
toxicological drug screening. In addition, 32 clinical urine samples from
potential drug abusers were analyzed to assess the effect of PM changes on the
assay. The mean level of lactose was low in clinical samples and relatively low
in PM samples in which no drugs were found. Markedly elevated levels were seen in
many of the buprenorphine positive samples, suggesting intravenous
administration. Enzymatic methods could provide a simple and cost effective way
to assess the intravenous administration of OMT drugs or drugs of abuse. Very
high levels of glucose in urine may interfere with the assays. Furthermore, other
causes for elevated urine disaccharides, such as hypolactasia and increased
intestinal permeability, need to be considered in the interpretation of the
results. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27504931
TI - Top-down, in-plane GaAs nanowire MOSFETs on an Al2O3 buffer with a trigate oxide
from focused ion-beam milling and chemical oxidation.
AB - The top-down fabrication of an in-plane nanowire (NW) GaAs metal-oxide
semiconductor field-effect transistor (MOSFET) with a trigate oxide implemented
by liquid-phase chemical-enhanced oxidation (LPCEO) is reported. A 2 MUm long
channel having an effective cross section ~70 * 220 nm(2) is directly fabricated
into an epitaxial n (+)-GaAs layer. This in-plane NW structure is achieved by
focused ion beam (FIB) milling and hydrolyzation oxidation resulting in
electronic isolation from the substrate through a semiconductor-on-insulator
structure with an n (+)-GaAs/Al2O3 layer stack. The channel is epitaxially
connected to the MUm-scale source and drain within a single layer for a planar
MOSFET to avoid any issues of ohmic contact and LPCEO to the NW. To fabricate a
MOSFET, the top and the two sidewalls of the in-plane NW are oxidized by LPCEO to
relieve the surface damage from FIB as well as to transform these surfaces to a
~15 nm thick gate oxide. This trigate device has threshold voltage ~0.14 V and
peak transconductance ~35 MUS MUm(-1) with a subthreshold swing ~150 mV/decade
and on/off ratio of drain current ~10(3), comparable to the performance of bottom
up NW devices.
PMID- 27504932
TI - Chemoresistance of Lung and Breast Cancer Cells Growing Under Prolonged Periods
of Serum Starvation.
AB - The efficacy of chemotherapy is hindered by both tumor heterogeneity and acquired
or intrinsic multi-drug resistance caused by the contribution of multidrug
resistance proteins and stemness-associated prosurvival markers. Therefore,
targeting multi-drug resistant cells would be much more effective against cancer.
In this study, we characterized the chemoresistance properties of adherent
(anchorage-dependent) lung H460 and breast MCF-7 cancer cells growing under
prolonged periods of serum starvation (PPSS). We found that under PPSS, both cell
lines were highly resistant to Paclitaxel, Colchicine, Hydroxyurea, Obatoclax,
Wortmannin, and LY294002. Levels of several proteins associated with increased
stemness such as Sox2, MDR1, ABCG2, and Bcl-2 were found to be elevated in H460
cells but not in MCF-7 cells. While pharmacological inhibition of either MDR1,
ABCG2, Bcl-2 with Verapamil, Sorafenib, or Obatoclax, respectively decreased the
levels of their target proteins under routine culture conditions as expected,
such inhibition did not reverse PX resistance in PPSS conditions. Paradoxically,
treatment with inhibitors in serum-starved conditions produced an elevation of
their respective target proteins. In addition, we found that Digitoxin, an FDA
approved drug that decrease the viability of cancer cells growing under PPSS,
downregulates the expression of Sox2, MDR1, phospho- AKT, Wnt5a/b, and beta
catenin. Our data suggest that PPSS-induced chemoresistance is the result of
extensive rewiring of intracellular signaling networks and that multi-resistance
can be effectively overcome by simultaneously targeting multiple targets of the
rewired network. Furthermore, our PPSS model provides a simple and useful tool to
screen drugs for their ability to target multiple pathways of cancer resistance.
J. Cell. Physiol. 232: 2033-2043, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27504933
TI - Attention and associative learning in humans: An integrative review.
AB - This article presents a comprehensive survey of research concerning interactions
between associative learning and attention in humans. Four main findings are
described. First, attention is biased toward stimuli that predict their
consequences reliably (learned predictiveness). This finding is consistent with
the approach taken by Mackintosh (1975) in his attentional model of associative
learning in nonhuman animals. Second, the strength of this attentional bias is
modulated by the value of the outcome (learned value). That is, predictors of
high-value outcomes receive especially high levels of attention. Third, the
related but opposing idea that uncertainty may result in increased attention to
stimuli (Pearce & Hall, 1980), receives less support. This suggests that hybrid
models of associative learning, incorporating the mechanisms of both the
Mackintosh and Pearce-Hall theories, may not be required to explain data from
human participants. Rather, a simpler model, in which attention to stimuli is
determined by how strongly they are associated with significant outcomes, goes a
long way to account for the data on human attentional learning. The last main
finding, and an exciting area for future research and theorizing, is that learned
predictiveness and learned value modulate both deliberate attentional focus, and
more automatic attentional capture. The automatic influence of learning on
attention does not appear to fit the traditional view of attention as being
either goal-directed or stimulus-driven. Rather, it suggests a new kind of
"derived" attention.
PMID- 27504934
TI - A meta-analytic review of the association between perceived social support and
depression in childhood and adolescence.
AB - This meta-analysis evaluated the relation between social support and depression
in youth and compared the cumulative evidence for 2 theories that have been
proposed to explain this association: the general benefits (GB; also known as
main effects) and stress-buffering (SB) models. The study included 341 articles
(19% unpublished) gathered through a search in PsycINFO, PsycARTICLES, ERIC, and
ProQuest, and a hand search of 11 relevant journals. Using a random effects
model, the overall effect size based on k = 341 studies and N = 273,149
participants was r = .26 (95% CI [.24, .28]), with robust support for the GB
model and support for the SB model among medically ill youth. Stress-buffering
analyses suggest that different stressful contexts may not allow youth to fully
draw on the benefits of social support, and we propose value in seeking to better
understand both stress-buffering (effects of social support are enhanced) and
reverse stress-buffering (effects of social support are dampened) processes. Key
findings regarding other moderators include a different pattern of effect sizes
across various sources of support. In addition, gender differences were largely
absent from this study, suggesting that social support may be a more critical
resource for boys than is typically acknowledged. Results also demonstrated the
importance of using instruments with adequate psychometric support, with careful
consideration of methodological and conceptual issues. Building upon these
collective findings, we provide recommendations for theory and practice, as well
as recommendations for addressing limitations in the extant literature to guide
future investigations. (PsycINFO Database Record
PMID- 27504935
TI - Trait entitlement: A cognitive-personality source of vulnerability to
psychological distress.
AB - Psychological entitlement is a personality trait characterized by pervasive
feelings of deservingness, specialness, and exaggerated expectations. The present
review expands upon this understanding by conceptualizing entitlement as a
cognitive-personality vulnerability to psychological distress. A review of
research is conducted, and a novel, multipart model is described by which
entitlement may be seen as such a vulnerability. First, exaggerated expectations,
notions of the self as special, and inflated deservingness associated with trait
entitlement present the individual with a continual vulnerability to unmet
expectations. Second, entitled individuals are likely to interpret these unmet
expectations in ways that foster disappointment, ego threat, and a sense of
perceived injustice, all of which may lead to psychological distress indicators
such as dissatisfaction across multiple life domains, anger, and generally
volatile emotional responses. Furthermore, in the wake of disappointment, ego
threat, or perceived injustice, entitled individuals are likely to attempt to
bolster their entitled self-concept, leading to a reinforcement of entitled
beliefs, thereby initiating the cycle again. At each stage of this process,
entitlement presents the individual with the possibility of experiencing
distress, predisposes further risk factors for distress (e.g., the subsequent
steps in the model), and increases the risk of interpersonal conflict, again
leading to distress. A review of relevant empirical data suggests preliminary
support for this conceptual model of entitlement. (PsycINFO Database Record
PMID- 27504936
TI - Crystal structures of spleen tyrosine kinase in complex with novel inhibitors:
structural insights for design of anticancer drugs.
AB - : Spleen tyrosine kinase (SYK) is a cytosolic nonreceptor protein tyrosine kinase
that mediates key signal transduction pathways following the activation of immune
cell receptors. SYK regulates cellular events induced by the B-cell receptor and
Fc receptors with high intrinsic activity. Furthermore, SYK has been regarded as
an attractive target for the treatment of autoimmune diseases and cancers. Here,
we report the crystal structures of SYK in complex with seven newly developed
inhibitors (G206, G207, O178, O194, O259, O272, and O282) to provide structural
insights into which substituents of the inhibitors and binding regions of SYK are
essential for lead compound optimization. Our kinase inhibitors exhibited high
inhibitory activities against SYK, with half-maximal inhibitory concentrations
(IC50 ) of approximately 0.7-33 nm, but they showed dissimilar inhibitory
activities against KDR, RET, JAK2, JAK3, and FLT3. Among the seven SYK
inhibitors, O272 and O282 exhibited highly specific inhibitions against SYK,
whereas O194 exhibited strong inhibition of both SYK and FLT3. Three inhibitors
(G206, G207, and O178) more efficiently inhibited FLT3 while still substantially
inhibiting SYK activity. The binding mode analysis suggested that a highly
selective SYK inhibitor can be developed by optimizing the functional groups that
facilitate direct interactions with Asn499. DATABASE: The atomic coordinates and
structure factors for human SYK are in the Protein Data Bank under accession
codes 4XG2 (inhibitor-free form), 4XG3 (G206), 4XG4 (G207), 5GHV (O178), 4XG6
(O194), 4XG7 (O259), 4XG8 (O272), and 4XG9 (O282).
PMID- 27504937
TI - Novel pyrazolylphosphite- and pyrazolylphosphinite-ruthenium(ii) complexes as
catalysts for hydrogenation of acetophenone.
AB - The new compounds and potential ligands 2-(3,5-di-tert-butyl-1H-pyrazol-1
yl)ethyldiphenlyphosphinite (L1), 2-(3,5-di-tert-butyl-1H-pyrazol-1
yl)ethyldiethylphosphite (L2), 2-(3,5-di-tert-butyl-1H-pyrazol-1-yl)ethyl
diethylphosphite (L3) and 2-(3,5-diphenyl-1H-pyrazol-1-yl)ethyldiethylphosphite
(L4) were prepared from the reaction of (3,5-(disubstituted)pyrazol-1H-yl)ethanol
and the appropriate phosphine chloride. The phosphinite (L1) and phosphites (L2
L4) and 2-(3,5-diphenyl-1H-pyrazol-1-yl)ethyldiphenylphosphinite (L5) were
reacted with [Ru(p-cymene)Cl2]2 to afford the ruthenium(ii) complexes [Ru(p
cymene)Cl2(L1)] (1), [Ru(p-cymene)Cl2(L2)] (2), [Ru(p-cymene)Cl2(L3)] (3), [Ru(p
cymene)Cl2(L4)] (4), and [Ru(p-cymene)Cl2(L5)] (5). All ruthenium complexes were
characterized by a combination of NMR spectroscopy, elemental analysis and, in
selected cases, by single crystal X-ray crystallography. Complexes 1-5 and [Ru(p
cymene)Cl2(L6)] (6) (prepared from 2-(3,5-dimethyl-1H-pyrazol-1
yl)ethyldiphenylphosphinite (L6)) were investigated as catalysts for both
transfer and molecular hydrogenation of acetophenone to 1-phenylethanol. At 80
degrees C the percent conversion of acetophenone in transfer hydrogenation was
moderate to high over 10 h (42-87%); for molecular hydrogenation acetophenone,
conversions were as high as 98% in 6 h.
PMID- 27504938
TI - Validation of the Polish version of P-QoL questionnaire.
AB - OBJECTIVE: Pelvic organ prolapse (POP) is a common morbidity that affects many
women and significantly decreases quality of life. The severity and the impact of
the prolapse on the quality of life are important parameters in the management
and follow-up of affected patients. The aim of this validation study was to
validate the Polish version of the Prolapse Quality of Life questionnaire (P
QoL). MATERIAL AND METHODS: The P-QOL questionnaire was translated into Polish
and administered to women recruited from two gynecological outpatient clinics (n
= 231). Both symptomatic and asymptomatic women were included in the study and
examined in supine position using the Pelvic Organ Prolapse Quantification System
(POP-Q). The validity was assessed by comparing symptom scores and quality-of
life scores between symptomatic and asymptomatic women. RESULTS: A total number
of 154 symptomatic and 77 asymptomatic women were included. There was a strong
correlation between severity of the disease based on physical findings (POP-Q
scale) and the P-QoL scores in main prolapse quality-of-life domains. The overall
scores for each life domain were significantly different between symptomatic and
asymptomatic women (p < 0.001). All the questions regarding symptoms showed
significant differences (p < 0.001) between both groups. CONCLUSIONS: The Polish
version of P-QoL is a valid, reliable, and easily comprehensible instrument to
assess quality of life and symptoms in Polish-speaking women suffering from
urogenital prolapse.
PMID- 27504939
TI - The role of early determination of beta-human chorionic gonadotropin levels in
predicting the success of single-dose methotrexate treatment in ectopic
pregnancy.
AB - OBJECTIVE: The aim of the study was to determine the importance of beta-hCG level
on day 4 following methotrexate (MTX) administration, and the difference between
beta-hCG levels assessed on day 0 and day 4 in predicting treatment success.
MATERIAL AND METHODS: A total of 68 women with tubal pregnancy, treated with a
single dose of MTX, were selected for this retrospective study. RESULTS: The
success rate of single-dose MTX treatment in our clinic was 75% (51/68). Among 51
patients in whom MTX treatment was successful, 25 (36.8%) showed a decrease in
beta-hCG level of > 15% on days 0 and 4, and 44 (64.7%) showed a beta-hCG level
decrease of > 15% on days 4 and 7. For subjects with beta-hCG decrease of > 15%
on days 4 and 7, the standard error was 6.5%, and the area under the ROC curve
was 81.7%, while the corresponding values for days 0 and 4 were 7.2% and 64%,
respectively. CONCLUSIONS: A decrease of > 15 % in beta-hCG levels between days 0
and 4 does not seem to be a better predictor for success of single-dose MTX
treatment for ectopic pregnancy than between days 4 and 7. A statistically
significant difference was observed only in beta-hCG levels on day 7 in both,
successful and unsuccessful single-dose MTX groups.
PMID- 27504940
TI - Comparison of endometrial biopsy and postoperative hysterectomy specimen findings
in patients with atypical endometrial hyperplasia and endometrial cancer.
AB - OBJECTIVES: The aim of the study was to assess the concordance between the
preoperative endometrial sampling and microscopic examination of the hysterectomy
specimens in patients surgically treated for atypical endometrial hyperplasia and
endometrial carcinoma. MATERIAL AND METHODS: We analysed a group of 204 patients,
of whom 160 (78.43%) underwent surgical treatment for cancer of the corpus uteri
and 44 (21.57%) for atypical endometrial hyperplasia. The preoperative diagnosis
was based on the histological examination of endocervical and endometrial samples
obtained by fractional curettage and it was compared to the histological findings
at hysterectomy. The comparison was made for the basic diagnosis, the
histological type of the cancer and the grade of tumour differentiation. RESULTS:
When the histological types of cancer diagnosed in endometrial curettage and
hysterectomy specimens were com-pared, the concordance was observed in 134/160
patients (83.75%). The highest concordance was found for endometrioid carcinoma
(127/148 patients, 85.81%). The grade of tumour differentiation was accurate in
69.31% of patients. The highest concordance was for moderately differentiated
carcinomas. Of 44 patients who underwent surgical treatment for atypical
endometrial hyperplasia, the preoperative diagnosis was confirmed by the
postoperative histopathological examination in 21 patients (47.73%). In 15
patients (34.09%) endometrial cancer was diagnosed at hysterectomy. CONCLUSIONS:
In endometrial cancer our findings demonstrate a high level of concordance
between the histological diagnosis on endometrial curettage and at hysterectomy.
Own observations have confirmed that over 30% of patients undergoing surgical
treatment for atypical endometrial hyperplasia have concurrent endometrial cancer
which is determined by surgery.
PMID- 27504941
TI - Prognostic value of 18F-FDG PET/CT for identifying high- and low-risk endometrial
cancer patients.
AB - OBJECTIVES: To assess the usefulness of adding PET/CT as a preoperative test for
determining the extent of endometrial cancer and discriminating low- and high
risk patients to identify candidates for surgical staging. MATERIAL AND METHODS:
We retrospectively reviewed 86 patients with pathologically proven endometrial
cancer who had undergone preoperative 18F-FDG PET/CT. The prognostic
relationships between PET/CT parameters and pathology reports were assessed.
RESULTS: The SUVmax was significantly higher in patients with FIGO stage IB or
higher compared with those with stage IA; for stage III-IV compared with stage I
II; and for patients with lymph node metastasis compared with those without lymph
node metastasis. Using 6.70 as a cut-off for SUVmax, low-risk patients can be
identified with a sensitivity of 92.9%. CONCLUSIONS: PET/CT imaging can be used
not only for determining malignancy and lymph node involvement but also for
determining candidates for surgical staging with high sensitivity.
PMID- 27504942
TI - Antenatal corticosteroids and respiratory distress syndrome - the first Polish
national survey.
AB - OBJECTIVES: Our retrospective study aimed to evaluate the rate and the
appropriate use of antenatal corticosteroid therapy, and their effect on the
incidence and treatment of respiratory distress syndrome (RDS) and its
complications. MATERIAL AND METHODS: A retrospective analysis of clinical
practice in Poland was performed using standard investigating tools: a
questionnaire on the frequency of using antennal corticosteroids in the selected
centers, as well as neonatal data. A total of 987 newborns at <= 32 weeks of
gestation, treated in 54 centers (including 42 tertiary and 12 secondary referral
centers) over a period of 6 months in 2013, were deemed eligible. The study group
consisted of 749 newborns whose mothers received antenatal steroids. The non
steroid group included 238 newborns. RESULTS: Antenatal corticosteroids were
administered to 75.89% of the neonates from the study group, with 79% and 21%
receiving one and two courses, respectively. Children whose mothers received
prenatal steroids presented with less extensive radiographic changes typical of
RDS, and less often required surfactant therapy (70% vs. 78%; p = 0.0143). In the
group of children undergoing antenatal steroid therapy, the percentage of BPD was
lower (13.27% vs. 18.63%) (p = 0.0881). The mortality rates were 20.91% and
10.81% in controls and the study group, respectively (p = 0.0001). CONCLUSIONS:
The percentage of antenatal steroid use in secondary and tertiary referral
centers in Poland is unsatisfactorily low (76%). Antenatal corticosteroids
demonstrated high efficacy in decreasing severe forms of RDS, less need for
surfactant therapy, and reduced BPD and mortality rates.
PMID- 27504943
TI - Correlation between factor VII and PAI-1 genetic variants and recurrent
miscarriage.
AB - BACKGROUND: Polymorphisms which are presented below may be the cause of inherited
thrombophilia and may result in pregnancy loss. The hypothesis is based on a
number of cardiology studies which have confirmed the involvement of these
polymorphisms in thrombotic incidents. OBJECTIVES: To evaluate the role of
polymorphisms of factor VII gene (Arg353Gln, -122T > C) and PAI-1 gene (-675
4G/5G) in the etiology of recurrent miscarriage. MATERIAL AND METHODS: The study
group included 152 women with a positive history of >= 2 consecutive pregnancy
losses (114 and 38 women with 2 and >= 3 miscarriages, respectively), while 180
healthy women were recruited as controls. Genetic analysis was performed with the
use of PCR/RFLP. RESULTS: Lower frequency of Arg353/Gln353 was observed in women
with 2 and >= 3 miscarriages as compared to controls (21.1% vs. 23.9% and 13.2%
vs. 23.9%, respectively). The frequency of Gln353 was lower in women with >= 3
miscarriages as compared to controls (6.6% vs. 11.9%, p = ns). The frequency of
122TT was higher in women with >= 3 miscarriages as compared to controls (86.84%
vs. 76.67%, p = ns), whereas -122TC was more frequent in controls (13.16% vs.
22.78% in controls, p = ns). The frequency of -122T was higher in patients with
>= 3 abortions as compared to controls (93.42% vs. 88.06%, p = ns), and -122C was
observed more frequently in controls (6.58% vs. 11.94% in controls, p = ns).
There were no significant differences as far as the -675 4G/5G polymorphism was
concerned. CONCLUSIONS: The obtained results suggest a possible protective role
of Gln353 and -122C alleles in recurrent miscarriage.
PMID- 27504944
TI - Assessment of ultrasound and Doppler parameters in the third trimester of
pregnancy as predictors of adverse perinatal outcome in unselected pregnancies.
AB - OBJECTIVES: The aim of the study was to investigate ultrasound and Doppler
parameters in the third trimester of pregnancy as possible predictors of adverse
perinatal outcome in unselected pregnancies. MATERIAL AND METHODS: We performed a
retrospective cross-sectional study including unselected pregnant women be-tween
27 and 36 + 6 weeks of gestation. The following ultrasound and Doppler parameters
were assessed: estimated fetal weight (EFW) [g], EFW percentile, placental
maturity grade (Grannum classification), single vertical deepest pocket (SVDP) of
amniotic fluid [cm], amniotic fluid index (AFI) [cm], mean uterine artery (UtA)
pulsatility index (PI), umbilical artery (UA) PI, middle cerebral artery (MCA)
PI, MCA peak systolic velocity (PSV) [cm/s], and cerebroplacental ratio (CPR).
Adverse perinatal outcome was defined as Apgar score of < 7 at 1 min, birth
weight of < 2500 g at delivery, and gestational age of < 37 weeks at delivery.
The unpaired t test was used to compare the groups. RESULTS: AFI (p = 0.01), mean
UtA PI (p = 0.04) and mean UA PI (p = 0.03) were significantly different with
regard to the Apgar score at 1 min. EFW, EFW percentile, SVDP of amniotic fluid,
AFI, mean UtA PI, UA PI, and MCA PI were significantly different (p < 0.001) in
terms of birth weight. Placental maturity grade (p = 0.02), SVDP of the amniotic
fluid (p < 0.001), AFI (p < 0.001), mean UtA PI (p < 0.001), UA PI (p = 0.001),
and MCA PI (p < 0.001) were significantly different as far as gestational age at
delivery is concerned. CONCLUSION: Ultrasound and Doppler parameters may predict
adverse perinatal outcomes in unselected pregnancies in the third trimester of
pregnancy.
PMID- 27504945
TI - Chemotherapy-induced peripheral neuropathy - diagnosis, evolution and treatment.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent
neurologic complications experienced by patients receiving antineoplastic drugs.
Involvement of the peripheral nerves may have an important impact on daily activi
ties and lead to severe impairment of the patient's quality of life (QoL). It
seems to be of crucial importance to make a correct and early diagnosis of
polyneuropathy and, if possible, spare the patient unnecessary suffering or loss
of function. In the preceding article we have presented epidemiology, grading and
pathogenesis of the toxic CIPN. The purpose of this article is to review current
knowledge of diagnostic techniques, prevention and management strategies in the
context of CIPN.
PMID- 27504946
TI - Current methods for preimplantation genetic diagnosis.
AB - Preimplantation Genetic Diagnosis (PGD) used in assisted reproduction techniques
is designed to provide help for couples trying to conceive a child, as it helps
deliver healthy offspring. After in vitro fertilization, material is collected
from the oocyte (polar body), 3-day-old embryo, or increasingly often, from the
trophectoderm of a blastocyst. Selection of the diagnostic method depends on the
testing center, but methods such as aCGH (Comparative Genomic Hybridization
Array) and NGS (Next-Generation Sequencing) are supposed to have the highest
reliability and precision. This paper presents a review of the most important
methods used in PGD, their advantages and disadvantages as well as efficacy in
the procedures in which they are used.
PMID- 27504947
TI - Psychosocial aspects of infertility and its treatment.
AB - Nowadays, more and more couples face impediments associated with conception.
Infertility is related with experiencing psychological problems by both partners.
One of the infertility treatment procedures is in vitro fertilization. Using this
method has significant influence on patients and their family's psychology. This
essay reviews literature about IVF treatment and discusses the significance of
infertility to a couple, children development and psychosocial functioning, their
relation with parents and public opinion about in vitro fertilization.
PMID- 27504948
TI - Anti-Mullerian hormone: a critical factor for female fertility and reproductive
health.
AB - Anti-Mullerian hormone (AMH) is a glycoprotein produced by the granulosa cells of
preantral and small antral follicles. AMH concentrations reflect ovarian
physiology with high precision, thus serving as a more sensitive marker of the
ovarian re-serve than chronological age. This hormone plays a role in the
pathogenesis of menstrual disorders and fertility in both obesity and polycystic
ovary syndrome. The evaluation of AMH may also be useful in diagnosing or
monitoring therapy of granulosa cell ovarian tumors.
PMID- 27504949
TI - Zika virus intrauterine infections from the obstetrician's perspective.
AB - Zika virus (ZIKAV) infections could potentially occur in Poland due to
international travel made by its nationals to regions where the Aedes mosquito is
active. A causal relationship between prenatal ZIKAV infection and microcephaly
and other serious brain anomalies has been found due to the time association
between the infection in pregnancy and a presence of congenital nervous system
malformations, together with the detectable pathogen in amniotic fluid and
fetus's tissues. Two ZIKAV infection cases of pregnant women who were diagnosed
with fetal microcephaly in the state of Paraiba, Brazil, later described in
Ultrasound Obstetrics and Gynecology by Oliveira Mello et al. are discussed, in
the context of the possible introduction of ZIKAV into Poland and the role the
obstetrician should play in the detection and rapid reaction to potential
threats. According to recommendations of international agencies for disease
control and prevention, Polish obstetricians who take care of pregnant women and
of those planning to become pregnant in the nearest future, and declaring travels
to areas of the Aedes mosquito activity, should advise their patients to consider
postponing travel or if they must travel, to take necessary precautionary
measures to avoid mosquito bites. Pregnant women who have travelled to areas with
ZIKAV transmission, or whose male partners had travelled to such areas and
returned in the period of their female part-ner's pregnancy, should be monitored
appropriately in the context of congenital abnormalities, including microcephaly.
PMID- 27504951
TI - Dense, Regular GaAs Nanowire Arrays by Catalyst-Free Vapor Phase Epitaxy for
Light Harvesting.
AB - Density dependent growth and optical properties of periodic arrays of GaAs
nanowires (NWs) by fast selective area growth MOVPE are investigated. As the
period of the arrays is decreased from 500 nm down to 100 nm, a volume growth
enhancement by a factor of up to four compared with the growth of a planar layer
is observed. This increase is explained as resulting from increased collection of
precursors on the side walls of the nanowires due to the gas flow redistribution
in the space between the NWs. Normal spectral reflectance of the arrays is
strongly reduced compared with a flat substrate surface in all fabricated arrays.
Electromagnetic modeling reveals that this reduction is caused by antireflective
action of the nanowire arrays and nanowire-diameter dependent light absorption.
Irrespective of the periodicity and diameter, Raman scattering and grazing angle
X-ray diffraction show signal from zinc blende and wurtzite phases, the latter
originating from stacking faults as observed by high resolution transmission
electron microscopy. Raman spectra contain intense surface phonons peaks, whose
intensity depends strongly on the nanowire diameters as a result of potential
structural changes and as well as variations of optical field distribution in the
nanowires.
PMID- 27504953
TI - The 4(th) MS Food Day Conference: mass spectrometry applications in food
analysis.
PMID- 27504950
TI - Use of a Cholesterol Recognition Amino Acid Consensus Peptide To Inhibit Binding
of a Bacterial Toxin to Cholesterol.
AB - Recognition of and binding to cholesterol on the host cell membrane is an initial
step in the mechanism of numerous pathogens, including viruses, bacteria, and
bacterial toxins; however, a viable method of inhibiting this interaction has not
yet been uncovered. Here, we describe the mechanism by which a cholesterol
recognition amino acid consensus peptide interacts with cholesterol and inhibits
the activity of a cholesterol-binding bacterial leukotoxin (LtxA). Using a series
of biophysical techniques, we have shown that the peptide recognizes the hydroxyl
group of cholesterol with nanomolar affinity and does not disrupt membrane
packing, suggesting that it sits primarily near the membrane surface. As a
result, LtxA is unable to bind to cholesterol or subsequently become internalized
in host cells. Additionally, because cholesterol is not being removed from the
cell membrane, the peptide-treated target cells remain viable over extended
periods of time. We have demonstrated the use of this peptide in the inhibition
of toxin activity for an antivirulence approach to the treatment of bacterial
disease, and we anticipate that this approach might have broad utility in the
inhibition of viral and bacterial pathogenesis.
PMID- 27504952
TI - Genetic Barrier to Direct Acting Antivirals in HCV Sequences Deposited in the
European Databank.
AB - BACKGROUND & AIMS: Development of resistance results from mutations in the viral
genome, and the presence of selective drug pressure leads to the emergence of a
resistant virus population. The aim of this study was to analyze the impact of
genetic variability on the genetic barrier to drug resistance to DAAs. METHODS:
The genetic barrier was quantified based on the number and type of nucleotide
mutations required to impart resistance, considering full-length HCV NS3, NS5A
and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This
study analyzeds 789 NS3 sequences, 708 sequences and 536 NS5B sequences deposited
in the European Hepatitis C Virus Database, in the following resistance
associated positions: NS3: F43/I/L/S/V, Q80K/R, R155K/G, A156G/S/T and
D168A/C/E/G/H/N/T/V/Y; NS5A: L/M28A/T/V, Q30E/H/R, L31F/I/M/V, H58D or P58S and
Y93C/F/H/N/S; NS5B: S282P/R/T, C316H/N/Y, S368T, Y448C/H, S556G/R, D559R.
RESULTS: Variants that require only one transversion in NS3 were found in 4
positions and include F43S, R80K, R155K/G and A156T. The genetic barrier to
resistance shows subtypic differences at position 155 of the NS3 gene where a
single transition is necessary in subtype 1a. In the NS5A gene, 5 positions where
only one nucleotide change can confer resistance were found, such as L31M which
requires one transversion in all subtypes, except in 0.28% of 1b sequences; and
R30H, generated by a single transition, which was found in 10.25% of the
sequences of genotype 1b. Other subtypic differences were observed at position
58, where resistance is less likely in genotype 1a because a transversion is
required to create the variant 58S. For the NS5B inhibitors, the genetic barrier
at positions conferring resistance was nearly identical in subtypes 1a and 1b,
and single transitions or transversions were necessary in 5 positions to generate
a drug-resistant variant of HCV. The positions C316Y and S556D required only one
transition in all genotypes, Y448H and S556 G/N/R positions required only one
transition for up to 98.8% of the sequences analyzed. A single variant in
position 448 in genotype 1a is less likely to become the resistance variant 448H
because it requires two transversions. Also, in the position 559D a transversion
and a transition were necessary to generate the resistance mutant D559H.
CONCLUSION: Results revealed that in 14 out of 16 positions, conversion to a drug
resistant variant of HCV required only one single nucleotide substitutions
threatening direct acting antivirals from all three classes.
PMID- 27504954
TI - Evaluation of a Urine Pooling Strategy for the Rapid and Cost-Efficient
Prevalence Classification of Schistosomiasis.
AB - BACKGROUND: A key epidemiologic feature of schistosomiasis is its focal
distribution, which has important implications for the spatial targeting of
preventive chemotherapy programs. We evaluated the diagnostic accuracy of a urine
pooling strategy using a point-of-care circulating cathodic antigen (POC-CCA)
cassette test for detection of Schistosoma mansoni, and employed simulation
modeling to test the classification accuracy and efficiency of this strategy in
determining where preventive chemotherapy is needed in low-endemicity settings.
METHODOLOGY: We performed a cross-sectional study involving 114 children aged 6
15 years in six neighborhoods in Azaguie Ahoua, south Cote d'Ivoire to
characterize the sensitivity and specificity of the POC-CCA cassette test with
urine samples that were tested individually and in pools of 4, 8, and 12. We used
a Bayesian latent class model to estimate test characteristics for individual POC
CCA and quadruplicate Kato-Katz thick smears on stool samples. We then developed
a microsimulation model and used lot quality assurance sampling to test the
performance, number of tests, and total cost per school for each pooled testing
strategy to predict the binary need for school-based preventive chemotherapy
using a 10% prevalence threshold for treatment. PRINCIPAL FINDINGS: The
sensitivity of the urine pooling strategy for S. mansoni diagnosis using pool
sizes of 4, 8, and 12 was 85.9%, 79.5%, and 65.4%, respectively, when POC-CCA
trace results were considered positive, and 61.5%, 47.4%, and 30.8% when POC-CCA
trace results were considered negative. The modeled specificity ranged from 94.0
97.7% for the urine pooling strategies (when POC-CCA trace results were
considered negative). The urine pooling strategy, regardless of the pool size,
gave comparable and often superior classification performance to stool microscopy
for the same number of tests. The urine pooling strategy with a pool size of 4
reduced the number of tests and total cost compared to classical stool
microscopy. CONCLUSIONS/SIGNIFICANCE: This study introduces a method for rapid
and efficient S. mansoni prevalence estimation through examining pooled urine
samples with POC-CCA as an alternative to widely used stool microscopy.
PMID- 27504955
TI - Use of systemic therapy with definitive radiotherapy for elderly patients with
head and neck cancer: A National Cancer Data Base analysis.
AB - BACKGROUND: The purpose of this study was to investigate the use of systemic
therapy along with definitive radiotherapy for elderly patients with head and
neck cancer. METHODS: Patients who were 71 years old or older with stage III to
IVB squamous cell carcinoma of the nasopharynx, oropharynx, larynx, or
hypopharynx treated with definitive radiotherapy with or without systemic therapy
were identified from the National Cancer Data Base. Patterns of systemic therapy
use before or during definitive radiotherapy were investigated. The association
between systemic therapy use and overall survival was investigated with a
multivariate, inverse probability-weighted propensity score-adjusted Cox
proportional hazards model. RESULTS: Elderly patients treated between 2004 and
2012 (n = 4165) were identified, and 80.4% received systemic therapy. The median
follow-up was 26 months (range, 1.8-125 months), and the 3-year overall survival
rate was 51.6% (95% confidence interval, 50.0%-53.2%). During the study period,
there was an increase in the frequency of systemic therapy use from 64% in 2004
to 86% in 2012. The use of systemic therapy was associated with improved overall
survival in the multivariate model (hazard ratio, 1.456; 95% confidence interval,
1.308-1.620; P < .0001). A threshold age above which the use of systemic therapy
was not associated with improved overall survival in select patients was not
identified. CONCLUSIONS: In contrast to the available prospective evidence, the
majority of elderly patients with locoregionally advanced head and neck cancer
treated with definitive radiotherapy also receive systemic therapy. The use of
systemic therapy is associated with improved overall survival and should be a
patient-specific decision in all age groups. Cancer 2016;122:3472-3483. (c) 2016
American Cancer Society.
PMID- 27504956
TI - The Grapevine Uncharacterized Intrinsic Protein 1 (VvXIP1) Is Regulated by
Drought Stress and Transports Glycerol, Hydrogen Peroxide, Heavy Metals but Not
Water.
AB - A MIP (Major Intrinsic Protein) subfamily called Uncharacterized Intrinsic
Proteins (XIP) was recently described in several fungi and eudicot plants. In
this work, we cloned a XIP from grapevine, VvXIP1, and agrobacterium-mediated
transformation studies in Nicotiana benthamiana revealed that the encoded
aquaporin shows a preferential localization at the endoplasmic reticulum
membrane. Stopped-flow spectrometry in vesicles from the aqy-null yeast strain
YSH1172 overexpressing VvXIP1 showed that VvXIP1 is unable to transport water but
is permeable to glycerol. Functional studies with the ROS sensitive probe CM
H2DCFDA in intact transformed yeasts showed that VvXIP1 is also able to permeate
hydrogen peroxide (H2O2). Drop test growth assays showed that besides glycerol
and H2O2, VvXIP1 also transports boric acid, copper, arsenic and nickel.
Furthermore, we found that VvXIP1 transcripts were abundant in grapevine leaves
from field grown plants and strongly repressed after the imposition of severe
water-deficit conditions in potted vines. The observed downregulation of VvXIP1
expression in cultured grape cells in response to ABA and salt, together with the
increased sensitivity to osmotic stress displayed by the aqy-null yeast
overexpressing VvXIP1, corroborates the role of VvXIP1 in osmotic regulation
besides its involvement in H2O2 transport and metal homeostasis.
PMID- 27504957
TI - Effect of Edible and Active Coating (with Rosemary and Oregano Essential Oils) on
Beef Characteristics and Consumer Acceptability.
AB - The effects of an alginate-based edible coating containing natural antioxidants
(rosemary and oregano essential oils) on lipid oxidation, color preservation,
water losses, texture and pH of beef steaks during 14 days of display were
studied. The essential oil, edible coating and beef antioxidant activities, and
beef consumer acceptability were also investigated. The edible coatings decreased
lipid oxidation of the meat compared to the control. The coating with oregano was
most effective (46.81% decrease in lipid oxidation) and also showed the highest
antioxidant activity. The coatings significantly decreased color losses, water
losses and shear force compared to the control. The coatings had a significant
effect on consumer perception of odor, flavor and overall acceptance of the beef.
In particular, the oregano coating showed significantly high values
(approximately 7 in a 9-point scale). Active edible coatings containing natural
antioxidants could improve meat product stability and therefore have potential
use in the food industry.
PMID- 27504958
TI - Therapeutic potential of recombinant thrombomodulin for lung injury after
pneumonectomy via inhibition of high-mobility group box 1 in mice.
AB - BACKGROUND: Surgical acute respiratory distress syndrome (ARDS) is an extremely
critical condition which may occur after major lung resection. Despite advances
in minimally invasive surgical procedures and progress in the therapeutic
management of this disease, prognosis remains poor. In this study, we
investigated the contribution of high-mobility group box 1 (HMGB1) in a surgical
ARDS model and evaluated the possible therapeutic effect of recombinant
thrombomodulin (rTM) for the treatment of surgical ARDS. METHODS: C57BL/6J mice
underwent left pneumonectomy. rTM was injected at 12 hours before surgery,
followed by 12 hours for 3 days after surgery. Lipopolysaccharide (LPS) was
administered at 2 hours after surgery. We conducted a histologic analysis and
measured HMGB1, IL-6, IL-1beta, and TNF-alpha in bronchoalveolar lavage fluid on
day 3 after pneumonectomy. Data were compared between the treatment groups.
RESULTS: On histologic analysis, left pneumonectomy followed by LPS
administration induced both severe inflammatory cellular infiltration and
alveolar wall congestion with hemorrhage. rTM administration rescued these
histologic changes. The level of HMGB1, IL-6, IL-1beta, and TNF-alpha in
bronchoalveolar lavage fluid was significantly increased by LPS administration
after pneumonectomy and significantly decreased by rTM administration with LPS
and pneumonectomy (p < 0.001). Also, LPS alone showed no statistical differences
in HMGB1 or proinflammatory cytokine level compared with pneumonectomy (PNX)
group. In addition, the survival outcome was also improved by rTM administration.
CONCLUSIONS: LPS administration after left pneumonectomy could induce the severe
lung injury. PNX and LPS have similar contribution to this model and may play a
synergistic role in this process. rTM may have the potential therapeutic effect
for surgical ARDS via suppression of HMGB1 and the secretion of proinflammatory
cytokines induced by the administration of LPS after left pneumonectomy.
PMID- 27504959
TI - Environmental Life Cycle Assessment of Diets with Improved Omega-3 Fatty Acid
Profiles.
AB - A high incidence of cardiovascular disease is observed worldwide, and dietary
habits are one of the risk factors for these diseases. Omega-3 polyunsaturated
fatty acids in the diet help to prevent cardiovascular disease. We used life
cycle assessment to analyse the potential of two strategies to improve the
nutritional and environmental characteristics of French diets: 1) modifying diets
by changing the quantities and proportions of foods and 2) increasing the omega-3
contents in diets by replacing mainly animal foods with equivalent animal foods
having higher omega-3 contents. We also investigated other possibilities for
reducing environmental impacts. Our results showed that a diet compliant with
nutritional recommendations for macronutrients had fewer environmental impacts
than the current average French diet. Moving from an omnivorous to a vegetarian
diet further reduced environmental impacts. Increasing the omega-3 contents in
animal rations increased Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid
(DHA) in animal food products. Providing these enriched animal foods in human
diets increased their EPA and DHA contents without affecting their environmental
impacts. However, in diets that did not contain fish, EPA and DHA contents were
well below the levels recommended by health authorities, despite the inclusion of
animal products enriched in EPA and DHA. Reducing meat consumption and avoidable
waste at home are two main avenues for reducing environmental impacts of diets.
PMID- 27504960
TI - Adjuvant Trastuzumab in HER2-Positive Early Breast Cancer by Age and Hormone
Receptor Status: A Cost-Utility Analysis.
AB - BACKGROUND: The anti-human epidermal growth factor receptor 2 (HER2) monoclonal
antibody trastuzumab improves outcomes in patients with node-positive HER2+ early
breast cancer. Given trastuzumab's high cost, we aimed to estimate its cost
effectiveness by heterogeneity in age and estrogen receptor (ER) and progesterone
receptor (PR) status, which has previously been unexplored, to assist
prioritisation. METHODS AND FINDINGS: A cost-utility analysis was performed using
a Markov macro-simulation model, with a lifetime horizon, comparing a 12-mo
regimen of trastuzumab with chemotherapy alone using the latest (2014)
effectiveness measures from landmark randomised trials. A New Zealand (NZ) health
system perspective was adopted, employing high-quality national administrative
data. Incremental quality-adjusted life-years for trastuzumab versus chemotherapy
alone are two times higher (2.33 times for the age group 50-54 y; 95% CI 2.29
2.37) for the worst prognosis (ER-/PR-) subtype compared to the best prognosis
(ER+/PR+) subtype, causing incremental cost-effectiveness ratios (ICERs) for the
former to be less than half those of the latter for the age groups from 25-29 to
90-94 y (0.44 times for the age group 50-54 y; 95% CI 0.43-0.45). If we were to
strictly apply an arbitrary cost-effectiveness threshold equal to the NZ gross
domestic product per capita (2011 purchasing power parity [PPP]-adjusted:
US$30,300; ?23,700; L21,200), our study suggests that trastuzumab (2011 PPP
adjusted US$45,400/?35,900/L21,900 for 1 y at formulary prices) may not be cost
effective for ER+ (which are 61% of all) node-positive HER2+ early breast cancer
patients but cost-effective for ER-/PR- subtypes (37% of all cases) to age 69 y.
Market entry of trastuzumab biosimilars will likely reduce the ICER to below this
threshold for premenopausal ER+/PR- cancer but not for ER+/PR+ cancer.
Sensitivity analysis using the best-case effectiveness measure for ER+ cancer had
the same result. A key limitation was a lack of treatment-effect data by hormone
receptor subtype. Heterogeneity was restricted to age and hormone receptor
status; tumour size/grade heterogeneity could be explored in future work.
CONCLUSIONS: This study highlights how cost-effectiveness can vary greatly by
heterogeneity in age and hormone receptor subtype. Resource allocation and
licensing of subsidised therapies such as trastuzumab should consider demographic
and clinical heterogeneity; there is currently a profound disconnect between how
funding decisions are made (largely agnostic to heterogeneity) and the principles
of personalised medicine.
PMID- 27504961
TI - Trauma and psychological distress in Latino citizen children following parental
detention and deportation.
AB - : The mental health impact of parental detention and deportation on citizen
children is a topic of increasing concern. Forced parent-child separation and
parental loss are potentially traumatic events (PTEs) with adverse effects on
children's mental health. OBJECTIVE: This study examines posttraumatic stress
disorder (PTSD) symptoms and psychological distress among 91 Latino U.S.-born
children (ages 6 to 12), living in mixed-status families with a least 1
undocumented parent at risk for detention or deportation. METHOD: Multiagent
(child, parent, teacher, clinician) and standardized assessments were conducted
at baseline to assess for child trauma and psychological distress. RESULTS:
Analyses indicate that PTSD symptoms as reported by parent were significantly
higher for children of detained and deported parents compared to citizen children
whose parents were either legal permanent residents or undocumented without prior
contact with immigration enforcement. Similarly, findings revealed differences in
child internalizing problems associated with parental detention and deportation
as reported by parent as well as differences in overall child functioning as
reported by clinician. In addition, teachers reported higher externalizing for
children with more exposure to PTEs. CONCLUSIONS: These findings lend support to
a reconsideration and revision of immigration enforcement practices to take into
consideration the best interest of Latino citizen children. Trauma-informed
assessments and interventions are recommended for this special population.
(PsycINFO Database Record
PMID- 27504962
TI - Role of Islamic appraisals, trauma-related appraisals, and religious coping in
the posttraumatic adjustment of Muslim trauma survivors.
AB - OBJECTIVE: This research investigated the role of Islamic appraisals, trauma
related appraisals, and religious coping in Muslim trauma survivors. METHOD: We
report 2 studies of Muslim trauma survivors with and without posttraumatic stress
disorder (PTSD) living in the United Kingdom (Study 1) and a sample of Muslim
trauma survivors living in Northern Iraq (Study 2). In both studies participants
completed the Posttraumatic Stress Diagnostic Scale, Brief Religious Coping
Scale, Islamic Appraisal Questionnaire, and Posttraumatic Cognitions Inventory in
Arabic. RESULTS: First, it was found that negative religious coping
differentiated between trauma survivors with and without PTSD (Study 1) and was
significantly correlated with PTSD symptoms (Study 2). Second, negative Islamic
appraisals were significantly associated with greater PTSD symptoms whereas
positive Islamic appraisals were significantly associated with fewer PTSD
symptoms (Study 2). Third, negative trauma-related appraisals correlated
significantly with, and uniquely predicted, PTSD symptoms (Study 2). Finally,
trauma-related appraisals were found to mediate the relationship between negative
Islamic appraisals and negative religious coping and PTSD symptoms. CONCLUSIONS:
These findings suggest that the theoretical emphasis on trauma-related cognitions
may also be applicable to our understanding of PTSD in Muslim trauma survivors.
However, for this population, trauma-related appraisals and subsequent coping
strategies may be influenced by Islamic beliefs and values. Clinically, our
findings suggest that addressing PTSD symptoms in Muslim trauma survivors may
require clinicians to consider the impact of trauma on the survivor's religious
appraisals and relationship with God. (PsycINFO Database Record
PMID- 27504963
TI - Aromatic Cluster Sensor of Protein Folding: Near-UV Electronic Circular Dichroism
Bands Assigned to Fold Compactness.
AB - Both far- and near-UV electronic circular dichroism (ECD) spectra have bands
sensitive to thermal unfolding of Trp and Tyr residues containing proteins.
Beside spectral changes at 222 nm reporting secondary structural variations (far
UV range), Lb bands (near-UV range) are applicable as 3D-fold sensors of
protein's core structure. In this study we show that both Lb (Tyr) and Lb (Trp)
ECD bands could be used as sensors of fold compactness. ECD is a relative method
and thus requires NMR referencing and cross-validation, also provided here. The
ensemble of 204 ECD spectra of Trp-cage miniproteins is analysed as a training
set for "calibrating" Trp<->Tyr folded systems of known NMR structure. While in
the far-UV ECD spectra changes are linear as a function of the temperature, near
UV ECD data indicate a non-linear and thus, cooperative unfolding mechanism of
these proteins. Ensemble of ECD spectra deconvoluted gives both conformational
weights and insight to a protein folding<->unfolding mechanism. We found that the
Lb293 band is reporting on the 3D-structure compactness. In addition, the pure
near-UV ECD spectrum of the unfolded state is described here for the first time.
Thus, ECD folding information now validated can be applied with confidence in a
large thermal window (5<=T<=85 degrees C) compared to NMR for studying the
unfolding of Trp<->Tyr residue pairs. In conclusion, folding propensities of
important proteins (RNA polymerase II, ubiquitin protein ligase, tryptase
inhibitor etc.) can now be analysed with higher confidence.
PMID- 27504964
TI - Dermoscopy of trichofolliculoma: a rare hair follicle hamartoma.
PMID- 27504965
TI - Accuracy of an International Classification of Diseases Code Surveillance System
in the Identification of Traumatic Brain Injury.
AB - BACKGROUND: Use of International Classification of Disease (ICD) codes for
traumatic brain injury (TBI) in healthcare administrative databases may
underestimate the epidemiology of TBI. The present study examined the use of ICD
10 codes in a population-based New Zealand sample. METHODS: TBI related ICD-codes
within the New Zealand health database were examined for all incident cases from
a population-based TBI sample (n = 1,369). Impact of age, gender, ethnicity,
presence/absence of skull fracture, where the case was located (i.e., hospital)
on receipt of an ICD code was examined. RESULTS: Individuals who received a TBI
related ICD-code accounted for 18.6% of the studied population. The most frequent
codes were brief loss of consciousness, head injury not otherwise specified, and
concussion. Receipt of a code was not impacted by gender. Those with skull
fracture (chi2 (1) = 69.983, p < 0.001), and/or attending hospital (chi2 (2) =
81.507, p < 0.001), and of older age (chi2 (1) = 56.473, p < 0.001) were more
likely to receive a code. CONCLUSIONS: Reported incidence of TBI, when based upon
health registration data, is likely to be a significant underestimate. Specific
research needs to be conducted to identify the barriers to medical personnel
implementing the ICD head injury codes and to identify ways in which the use of
the codes can be improved.
PMID- 27504966
TI - Ruthenium-Catalyzed Hydroalkynylative Cyclization of 1,6-Enynes Induced by
Substituent Effects.
AB - The ruthenium-catalyzed 1,6-enyne cyclization in the presence of bulky
substituted terminal alkyne proceeds smoothly at room temperature to afford
highly substituted five-membered cyclic compounds featuring a 1,5-enyne motif.
Deuterium-labeling experiments showed that the key ruthenacyclopentene
intermediate undergoes cleavage of metal-carbon bonds through the metal-assisted
sigma-bond metathesis reaction, thus leading to the formation of C(sp(2))-H and
C(sp(3))-C(sp) bonds.
PMID- 27504967
TI - Hearing lessons from flies.
AB - Studying the auditory system of the fruit fly can reveal how hearing works in
mammals.
PMID- 27504968
TI - Septin/anillin filaments scaffold central nervous system myelin to accelerate
nerve conduction.
AB - Myelination of axons facilitates rapid impulse propagation in the nervous system.
The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal
aging. However, the molecular cause of many pathological features, including the
frequently observed myelin outfoldings, remained unknown. Using label-free
quantitative proteomics, we find that the presence of myelin outfoldings
correlates with a loss of cytoskeletal septins in myelin. Regulated by
phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins
(SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously
unrecognized filaments that extend longitudinally along myelinated axons. By
confocal microscopy and immunogold-electron microscopy, these filaments are
localized to the non-compacted adaxonal myelin compartment. Genetic disruption of
these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific
neuropathology. Septin filaments thus serve an important function in scaffolding
the axon/myelin-unit, evidently a late stage of myelin maturation. We propose
that pathological or aging-associated diminishment of the septin/anillin-scaffold
causes myelin outfoldings that impair the normal nerve conduction velocity.
PMID- 27504970
TI - Effects of Nitrogen Availability and Form on Phytoplankton Growth in a Eutrophied
Estuary (Neuse River Estuary, NC, USA).
AB - Nitrogen availability and form are important controls on estuarine phytoplankton
growth. This study experimentally determined the influence of urea and nitrate
additions on phytoplankton growth throughout the growing season (March 2012, June
2011, August 2011) in a temperate, eutrophied estuary (Neuse River Estuary, North
Carolina, USA). Photopigments (chlorophyll a and diagnostic photopigments:
peridinin, fucoxanthin, alloxanthin, zeaxanthin, chlorophyll b) and microscopy
based cell counts were used as indicators of phytoplankton growth. In March, the
phytoplankton community was dominated by Gyrodinium instriatum and only
fucoxanthin-based growth rates were stimulated by nitrogen addition. The limited
response to nitrogen suggests other factors may control phytoplankton growth and
community composition in early spring. In June, inorganic nitrogen concentrations
were low and stimulatory effects of both nitrogen forms were observed for
chlorophyll a- and diagnostic photopigment-based growth rates. In contrast, cell
counts showed that only cryptophyte and dinoflagellate (Heterocapsa rotundata)
growth were stimulated. Responses of other photopigments may have been due to an
increase in pigment per cell or growth of plankton too small to be counted with
the microscopic methods used. Despite high nitrate concentrations in August,
growth rates were elevated in response to urea and/or nitrate addition for all
photopigments except peridinin. However, this response was not observed in cell
counts, again suggesting that pigment-based growth responses may not always be
indicative of a true community and/or taxa-specific growth response. This
highlights the need to employ targeted microscopy-based cell enumeration
concurrent with pigment-based technology to facilitate a more complete
understanding of phytoplankton dynamics in estuarine systems. These results are
consistent with previous studies showing the seasonal importance of nitrogen
availability in estuaries, and also reflect taxa-specific responses nitrogen
availability. Finally, this study demonstrates that under nitrogen-limiting
conditions, the phytoplankton community and its various taxa are capable of using
both urea and nitrate to support growth.
PMID- 27504969
TI - A shared numerical representation for action and perception.
AB - Humans and other species have perceptual mechanisms dedicated to estimating
approximate quantity: a sense of number. Here we show a clear interaction between
self-produced actions and the perceived numerosity of subsequent visual stimuli.
A short period of rapid finger-tapping (without sensory feedback) caused subjects
to underestimate the number of visual stimuli presented near the tapping region;
and a period of slow tapping caused overestimation. The distortions occurred both
for stimuli presented sequentially (series of flashes) and simultaneously (clouds
of dots); both for magnitude estimation and forced-choice comparison. The
adaptation was spatially selective, primarily in external, real-world
coordinates. Our results sit well with studies reporting links between perception
and action, showing that vision and action share mechanisms that encode numbers:
a generalized number sense, which estimates the number of self-generated as well
as external events.
PMID- 27504971
TI - miR-4443 Participates in the Malignancy of Breast Cancer.
AB - PURPOSE: Chemo-resistance is the leading cause of failure in cancer therapy,
however, much remains to be understood about the intrinsic mechanisms. In the
present study, we discovered the novel miR-4443 that regulated malignancy of
breast cancer both in vitro and in vivo. METHODS: We examined the expression of
miR-4443 in MDA-MB-231/S and MDA-MB-231 Epirubicin-resistant cell lines with 76
breast cancer formalin-fixed paraffin-embedded tissues by real-time PCR. Also, we
investigated the loss- and gain-functions of miR-4443 by MTT assay and flow
cytometry. Furthermore, we detected miR-4443 mediated tissue inhibitor of
metalloproteinase 2 expression in cells by TargetScan, RT-qPCR and western blot.
RESULTS: We identified the up-regulated expression of miR-4443 in Epi-resistant
cell lines versus MDA-MB-231/S cell(Epi versus S) and in post-chemotherapy FFPE
tissues, along with statistically differential expressions in PR(partial
response) versus SD(stable disease)/PD(progressive disease) patients.
Overexpression of miR-4443 increased the IC50 value of Epi for the target cells
transfected, while inhibition of miR-4443 could restored sensitivity of the
target cells to Epi. Besides, down-regulation of endogenous miR-4443 by miRNA
inhibitors significantly enhanced Epi-induced apoptosis while up-regulation of
miR-4443 by miRNA-mimics lead to less Epi-induced apoptotic cells. Consequently,
changes in TIMP2 mRNA and protein expression revealed that miR-4443 mimics
suppressed expression of TIMP2 and induced migration in breast cancer cells.
Furthermore, TIMP2 expression associated with better prognosis(HR = 0.721, 95%CI:
0.529-0.983). CONCLUSIONS: We revealed that miR-4443 induced malignancy of breast
cancer mainly in chemo-resistance aspect for the very first time, providing a
novel biomarker in breast cancer diagnosis and therapy.
PMID- 27504972
TI - Iron accumulates in the primate choroid of the eye with aging as revealed with
synchrotron X-ray fluorescence microscopy.
AB - Aging leads to an increase in iron-loaded cellular structures in the choroid of
the eye. This study was carried out to determine the distribution and content of
iron, zinc and copper in the macular retina, choroid and retrobulbar optic nerve
of young (4-5 years, n = 3) and aged (15-16 years, n = 5) male non-human
primates, Macaca fascicularis, whose ocular anatomy is similar to humans. Thirty
MUm-thick tissue sections were analysed with synchrotron X-ray fluorescence and
stained histologically for iron deposition. Quantitative measurements showed high
levels of iron, zinc and copper in the choroid and retinal pigment epithelium in
the macular area and arachnoid layer in the retrobulbar optic nerve. In aged
animals compared to young ones, there was an increase in iron in the choroid with
larger deposits and iron-loaded cellular structures. Iron-accumulation within
these cellular structures may contribute to choroidal function impairment in
aging and age-related macular degeneration.
PMID- 27504974
TI - Standardized Grading of Shock Wave Lithotripsy Complications with Modified
Clavien System.
AB - INTRODUCTION: Definitive consensus on grading of complications of shock wave
lithotripsy (SWL) does not exist. The objective of this study was to grade
complications of SWL in relation to different stone and shock wave parameters,
according to the modified Clavien system. MATERIALS AND METHODS: Complications
observed in 2,648 patients who underwent SWL between January 2003 and May 2014
were evaluated statistically and stratified into 5 grades by the modified Clavien
system focusing on stone and shock wave parameters. RESULTS: Statistically
significant association (p <= 0.05) was found between SWL outcome, Clavien grade
of complications and stone and shock wave parameters. According to the modified
Clavien system, grades I, II, IIIa, IIIb, IV and V complications were observed in
1,811 (68.39%), 619 (23.37%), 183 (6.91%), 34 (1.28%), nil (0.00%) and 1 (0.03%)
patients, respectively. The overall success rate at 3 months was 87.72%.
CONCLUSIONS: The modified Clavien system provides a standardized grading of SWL
complications and can be used to standardize procedural errors and maintain
quality, thereby preventing associated complications and improving the overall
management and hence outcome of SWL.
PMID- 27504973
TI - Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in
the TRAMP Mouse Model.
AB - Attenuated Salmonella typhimurium injected in the circulatory system of mammals
selectively targets tumors. Using weekly intraperitoneal injections of attenuated
Salmonella strain CRC2631, we tested for regression and/or inhibition of tumor
development in the TRAMP prostate tumor mouse model, which utilizes SV40 early
region expression for autochthonous formation of prostate tumors that progress
into metastatic, poorly differentiated prostatic carcinomas in an immunocompetent
murine model. Thirteen weekly intraperitoneal administrations of 105-107 CFU
CRC2631 into 10 week old mice were well tolerated by the TRAMP model. Sacrifice
and histological analysis of TRAMP prostates at 22 weeks indicated that
Salmonella monotherapy at administrated levels decrease visible tumor size (>29%)
but did not significantly inhibit previously described SV40 expression-driven
TRAMP tumor progression to undifferentiated carcinomas when histologically
examined. In conclusion, this work demonstrates baseline results for CRC2631
Salmonella monotherapy using the immunocompetent TRAMP prostate tumor model in
preparation for study of combination therapies that resolve autochthonously
generated TRAMP prostate tumors, further reduce tumor size, or inhibit prostate
tumor progression.
PMID- 27504975
TI - Evaluation of the Western blotting method for the diagnosis of congenital
toxoplasmosis.
AB - OBJECTIVE: To evaluate the Western blotting method for the detection of IgG anti
Toxoplasma gondii (T. gondii) (IgG-WB) in the serum of children with suspected
congenital toxoplasmosis. METHODS: We accompanied 47 mothers with acquired
toxoplasmosis in pregnancy and their children, between June of 2011 and June of
2014. The IgG-WB was done in house and the test was considered positive if the
child had antibodies that recognized at least one band on IgG blots different
from the mother's or with greater intensity than the corresponding maternal band,
during the first three months of life. RESULTS: 15 children (15.1%) met the
criteria for congenital toxoplasmosis and 32 (32.3%) had the diagnosis excluded.
The symptoms were observed in 12 (80.0%) children and the most frequent were
cerebral calcification in 9 (60.0%), chorioretinitis in 8 (53.3%), and
hydrocephalus in 4 (26.6%). IgM antibodies anti-T. gondii detected by
chemiluminescence (CL) were found in 6 (40.0%) children and the polymerase chain
reaction (PCR) for detection of T. gondii DNA was positive in 5 of 7 performed
(71.4%). The sensitivity of IgG-WB was of 60.0% [95% confidence interval (CI)
32.3-83.7%] and specificity 43.7% (95% CI 26.7-62.3%). The sensitivity of IgG-WB
increased to 76.0 and 89.1% when associated to the research of IgM anti-T. gondii
or PCR, respectively. CONCLUSIONS: The IgG-WB showed greater sensitivity than the
detection of IgM anti-T. gondii; therefore, it can be used for the diagnosis of
congenital toxoplasmosis in association with other congenital infection markers.
PMID- 27504976
TI - Early changes in adipokines from overweight to obesity in children and
adolescents.
AB - OBJECTIVE: Childhood obesity has been associated with metabolic syndrome and
cardiovascular diseases. This study aimed to compare plasma levels of traditional
metabolic markers, adipokines and soluble tumor necrosis factor receptor type 1
(sTNFR1) in overweight, obese and lean children. We also assessed the
relationships of these molecules with classical metabolic risk factors. METHODS:
This study included 104 children and adolescents, which were grouped as: lean
(n=24), overweight (n=30), and obese subjects (n=50). They were subjected to
anthropometrical, clinical and laboratorial measurements. All measurements were
compared between groups. Correlation analyses were also performed to evaluate the
association between clinical data, traditional metabolic markers, adipokines and
sTNFR1. RESULTS: Fasting glucose, insulin, homeostatic model assessment of
insulin resistance (HOMA-IR), LDL-cholesterol and triglycerides were comparable
in lean, overweight and obese subjects. Plasma levels of sTNFR1 were similar in
lean and overweight subjects, but significantly increased in obese group. Leptin,
adiponectin and resistin levels did not differ when overweight were compared to
obese subjects. However, all adipokines differed significantly when lean subjects
were compared to overweight and obese individuals. Plasma levels of adiponectin
were negatively correlated with body mass index (BMI), whereas leptin, resistin
and sTNFR1 concentrations positively correlated with BMI. CONCLUSION: Our results
showed significant differences in circulating levels of the evaluated markers
when lean, overweight and obese individuals were compared, suggesting that these
biomarkers may change from lean to overweight and from overweight to obesity.
PMID- 27504977
TI - Misuse of Substitution Drugs in the Substitution-Based Therapy.
AB - BACKGROUND: The reasons for, and the extent of, misuse of prescribed substitution
medication as well as parallel consumption of other drugs during substitution
based therapy have still not been adequately researched in Germany. METHODS: This
study examines the use of substitution medication in German substitution clinics
utilizing a nationwide survey with anonymised questionnaires. RESULTS: The
analysis of the 605 questionnaires showed a 30-day consumption prevalence of 8.8%
with regard to misuse of substitution substances. The lack of available heroin
(38%) and the lack of open spots in treatment programs (21%) were quoted as being
the main reasons for the misuse of substitution medication. CONCLUSION: Although
the misuse of substitution medications is considered an important problem, our
study showed that the current misuse was prevalent only among a minority of the
patients. German regulations focused on the avoidance of misuse might be
partially contributing to the problem.
PMID- 27504978
TI - Do organisational constraints explain the use of restraint? A comparative
ethnographic study from three nursing homes in Norway.
AB - AIMS AND OBJECTIVES: To investigate (1) what kind of restraint is used in three
nursing homes in Norway and (2) how staff use restraint under what organisational
conditions. BACKGROUND: Restraint use in residents living with dementia in
nursing homes is controversial, and at odds with fundamental human rights.
Restraint is a matter of hindering residents' free movement and will by applying
either interactional, physical, medical, surveillance or environmental restraint.
Previous research has identified use of restraint related to individual resident
characteristics such as agitation, aggressiveness and wandering. DESIGN: This
model is embedded in an overall mixed-method education intervention design study
called Modelling and evaluating evidence-based continuing education program in
dementia care (MEDCED), applying ethnography postintervention to examine the use
of restraint in 24 nursing homes in Norway. METHOD: Based on restraint diversity
measured in the trial, ethnographic investigation was carried out in three
different nursing homes in Norway over a 10-month period to examine restraint use
in relation to organisational constraints. RESULTS: Several forms of restraint
were observed; among them, interactional restraint was used most frequently. We
identified that use of restraint relates to the characteristics of individual
residents, such as agitation, aggressiveness and wandering. However, restraint
use should also be explained in relation to organisational conditions such as
resident mix, staff culture and available human resources. CONCLUSION: A
fluctuating and dynamic interplay between different individual and contextual
factors determines whether restraint is used - or not in particular situations
with residents living with dementia. RELEVANCE TO CLINICAL PRACTICE: Educational
initiatives targeting staff to reduce restraint must be sensitive towards
fluctuating organisational constraints.
PMID- 27504979
TI - Glucagon Like Peptide-1 Promotes Adipocyte Differentiation via the Wnt4 Mediated
Sequestering of Beta-Catenin.
AB - Glucagon-like peptide-1 (GLP-1) plays a role in the regulation of adipogenesis;
however, the precise underlying molecular mechanism has not been fully defined.
Wnt was recently identified as an important regulator of adipogenesis. This study
aimed to investigate the involvement of the Wnt signaling pathway in the effects
of GLP-1 on adipocyte differentiation. 3T3-L1 cells were induced to
differentiate. The changes in the expression levels of adipogenic transcription
factors and Wnts and the phosphorylation level and subcellular localization of
beta-catenin were quantified after GLP-1 treatment. GLP-1 stimulated adipocyte
differentiation and lipid accumulation, which were accompanied by the expression
of adipocyte marker genes. The expression of Wnt4 was upregulated in the process
of adipocyte differentiation, which was further enhanced by treatment with GLP-1.
beta-catenin, an important mediator of the Wnt pathway, was immediately
dephosphorylated and translocated from cytoplasm to nucleus when differentiation
was induced. In the presence of GLP-1, however, beta-catenin was redirected to
the cell plasma membrane leading to its decreased accumulation in the nucleus.
Knockdown of Wnt4 blocked the effect of GLP-1 on the cellular localization of
beta-catenin and expression level of adipogenic transcription factors. Our
findings showed that GLP-1 promoted adipogenesis through the modulation of the
Wnt4/beta-catenin signaling pathway, suggesting that the GLP-1-Wntbeta-catenin
system might be a new target for the treatment of metabolic disease.
PMID- 27504981
TI - Understanding How Isotopes Affect Charge Transfer in P3HT/PCBM: A Quantum
Trajectory-Electronic Structure Study with Nonlinear Quantum Corrections.
AB - The experimentally observed effect of selective deuterium substitution on the
open circuit voltage for a blend of poly(3-hexylthiophene) (P3HT) and [6,6]
phenyl-C61-butyric acid methyl ester (PCBM; Nat. Commun. 2014, 5, 3180) is
explored using a 221-atom model of a polymer-wrapped PCBM molecule. The protonic
and deuteronic wave functions for the H/D isotopologues of the hexyl side chains
are described within a quantum trajectory/electronic structure approach where the
dynamics is performed with newly developed nonlinear corrections to the quantum
forces, necessary to describe the nuclear wave functions; the classical forces
are generated with a density functional tight binding method. The resulting
protonic and deuteronic time-dependent wave functions are used to assess the
effects of isotopic substitution (deuteration) on the energy gaps relevant to the
charge transfer for the donor and acceptor electronic states. While the isotope
effect on the electronic energy levels is found negligible, the quantum-induced
fluctuations of the energy gap between the charge transfer and charge separated
states due to nuclear wave functions may account for experimental trends by
promoting charge transfer in P3HT:PCBM and increasing charge recombination on the
donor in the deuterium substituted P3HT:PCBM.
PMID- 27504980
TI - A Novel Approach to Helicobacter pylori Pan-Genome Analysis for Identification of
Genomic Islands.
AB - Genomes of a given bacterial species can show great variation in gene content and
thus systematic analysis of the entire gene repertoire, termed the pan-genome, is
important for understanding bacterial intra-species diversity, population
genetics, and evolution. Here, we analyzed the pan-genome from 30 completely
sequenced strains of the human gastric pathogen Helicobacter pylori belonging to
various phylogeographic groups, focusing on 991 accessory (not fully conserved)
orthologous groups (OGs). We developed a method to evaluate the mobility of genes
within a genome, using the gene order in the syntenically conserved regions as a
reference, and classified the 991 accessory OGs into five classes: Core, Stable,
Intermediate, Mobile, and Unique. Phylogenetic networks based on the gene content
of Core and Stable classes are highly congruent with that created from the
concatenated alignment of fully conserved core genes, in contrast to those of
Intermediate and Mobile classes, which show quite different topologies. By
clustering the accessory OGs on the basis of phylogenetic pattern similarity and
chromosomal proximity, we identified 60 co-occurring gene clusters (CGCs). In
addition to known genomic islands, including cag pathogenicity island,
bacteriophages, and integrating conjugative elements, we identified some novel
ones. One island encodes TerY-phosphorylation triad, which includes the eukaryote
type protein kinase/phosphatase gene pair, and components of type VII secretion
system. Another one contains a reverse-transcriptase homolog, which may be
involved in the defense against phage infection through altruistic suicide. Many
of the CGCs contained restriction-modification (RM) genes. Different RM systems
sometimes occupied the same (orthologous) locus in the strains. We anticipate
that our method will facilitate pan-genome studies in general and help identify
novel genomic islands in various bacterial species.
PMID- 27504982
TI - Accessory Anterolateral Talar Facet in Populations With and Without Symptoms:
Prevalence and Relevant Associated Ankle MRI Findings.
AB - OBJECTIVE: The purpose of this study was to determine the prevalence of and
relevant findings associated with the accessory anterolateral talar facet, which
may have a role in talocalcaneal impingement and sinus tarsi syndrome, on ankle
MR images of persons with and those without symptoms. SUBJECTS AND METHODS: In
this case-control study, three observers independently reviewed 1.5-T or 3-T MR
images of 110 ankles with symptoms in 100 consecutively registered patients (age
range, 16-79 years; mean, 41.5 years) and limited 1.5-T MR images of 104 age-,
sex-, and side-matched ankles in 104 volunteers without symptoms for the presence
of an accessory anterolateral talar facet, calcaneal cortical thickness,
subjacent talar or calcaneal cystic and bone marrow edema-like changes at the
angle of Gissane, and sinus tarsi fat obliteration. RESULTS: An accessory
anterolateral talar facet was present in 36 (32.7%) ankles with symptoms versus
27 (26.0%) symptom-free ankles (p = 0.297). Interobserver agreement was almost
perfect (kappa = 0.851; 95% CI, 0.772-0.929) for the detection of accessory
anterolateral talar facet and substantial for the detection of sinus tarsi fat
obliteration (kappa = 0.671; 95% CI, 0.427-0.915). The angle of Gissane was
significantly smaller in persons with an accessory anterolateral talar facet,
either with or without symptoms (p < 0.0001). Subjacent talar (p = 0.003) and
calcaneal (p = 0.033) bone marrow edema-like change and sinus tarsi fat
obliteration (p = 0.034) were significantly more frequent in persons with
accessory anterolateral talar facet, but chronic reactive osseous changes at the
angle of Gissane were not (p > 0.05). CONCLUSION: The higher prevalence of the
MRI finding of an accessory anterolateral talar facet in ankles with and without
symptoms is not statistically significant. This facet may be associated with
subjacent talar bone marrow edema-like change on MR images of individuals with
and those without symptoms and with sinus tarsi fat obliteration in individuals
with symptoms.
PMID- 27504983
TI - A test to identify persistent picky eaters.
AB - BACKGROUND: Picky eating is common and usually relatively brief as new foods are
accepted. Persistent picky eating, however, is often associated with comorbid
psychopathology. OBJECTIVE: The aim of this study was to use parent-reported
child feeding behaviors to identify which picky eaters persist. DESIGN:
Participants were a subsample from the Stanford Infant Growth Study a prospective
study of child development. Out of the 216 infants, 86 were identified as picky
eaters. Picky eaters were separated into two groups using a median split: short
term (n=40) and persistent picky eaters (n=46). RESULTS: Recursive Partitioning
detected three significant parent-reported feeding questions that may identify
persistent picky eaters at an early age: Is your child a picky eater? (yes), does
s/he have strong likes with regard to food (yes), does your child accept new
foods readily? (no). DISCUSSION: These results provide a first step allowing
providers to identify persistent picky eaters and possibly enable intervention at
an early age. Further studies are needed to replicate and extend these findings
in another sample of picky eaters.
PMID- 27504984
TI - Poly(I:C) Induces Human Lung Endothelial Barrier Dysfunction by Disrupting Tight
Junction Expression of Claudin-5.
AB - Viral infections are often accompanied by pulmonary microvascular leakage and
vascular endothelial dysfunction via mechanisms that are not completely defined.
Here, we investigated the effect of the Toll-like receptor 3 (TLR3) ligand
polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double
stranded RNA (dsRNA) commonly used to simulate viral infections, on the barrier
function and tight junction integrity of primary human lung microvascular
endothelial cells. Poly(I:C) stimulated IL-6, IL-8, TNFalpha, and IFNbeta
production in conjunction with the activation of NF-kappaB and IRF3 confirming
the Poly(I:C)-responsiveness of these cells. Poly(I:C) increased endothelial
monolayer permeability with a corresponding dose- and time-dependent decrease in
the expression of claudin-5, a transmembrane tight junction protein and reduction
of CLDN5 mRNA levels. Immunofluorescence experiments revealed disappearance of
membrane-associated claudin-5 and co-localization of cytoplasmic claudin-5 with
lysosomal-associated membrane protein 1. Chloroquine and Bay11-7082, inhibitors
of TLR3 and NF-kappaB signaling, respectively, protected against the loss of
claudin-5. Together, these findings provide new insight on how dsRNA-activated
signaling pathways may disrupt vascular endothelial function and contribute to
vascular leakage pathologies.
PMID- 27504985
TI - Olanzapine-depot administration induces time-dependent changes in adipose tissue
endocrine function in rats.
AB - OBJECTIVE: Metabolic adverse effects of atypical antipsychotics (AAP) contribute
significantly to increased risk of cardiovascular morbidity and mortality in
patients suffering from schizophrenia. Extensive preclinical research has
addressed this issue over the past years, though mechanisms underlying these
adverse effects of AAP are still not understood completely. Recently, attention
is drawn towards the role of adipose tissue metabolism and neurohormonal
regulations. METHODS: The aim of this study was to evaluate the time-dependent
effects of olanzapine depot administration at clinically relevant dosing on the
regulation of energy homeostasis, glucose and lipid metabolism, gastrointestinal
and adipose tissue-derived hormones involved in energy balance regulations in
female Sprague-Dawley rats. The study lasted 8 weeks and the markers were assayed
at day 8, 15, 29, 43 and 57. RESULTS: The results indicate that in the absence of
hyperphagia, olanzapine chronic exposure induced weight gain from the beginning
of the study. In the later time-point, increased adiposity was also observed. In
the initial phase of the study, lipid profile was altered by an early increase in
triglyceride level and highly elevated leptin level was observed. Clear bi-phasic
time-dependent effect of olanzapine on leptin serum concentration was
demonstrated. Olanzapine treatment did not lead to changes in serum levels of
ghrelin, FGF-21 and pro-inflammatory markers IL-1a, IL-6 and TNF-alpha at any
time-point of the study. CONCLUSION: This study provides data suggesting early
alteration in adipose tissue endocrine function as a factor involved in
mechanisms underlying metabolic adverse effects of antipsychotics.
PMID- 27504986
TI - Concentration-Dependent Proton Transfer Mechanisms in Aqueous NaOH Solutions:
From Acceptor-Driven to Donor-Driven and Back.
AB - Proton transfer processes play an important role in many fields of chemistry. In
dilute basic aqueous solutions, proton transfer from water molecules to hydroxide
ions is aided by "presolvation", i.e., thermal fluctuations that modify the
hydrogen-bonding environment around the proton-receiving OH(-) ion to become more
similar to that of a neutral H2O molecule. In particular at high concentrations,
however, the underlying mechanisms and especially the role of the counterions are
little understood. As a prototypical case, we investigate aqueous NaOH solutions
using molecular dynamics simulations employing a reactive high-dimensional neural
network potential constructed from density functional theory reference data. We
find that with increasing concentration the predominant proton transfer mechanism
changes from being "acceptor-driven", i.e., governed by the presolvation of OH(
), to "donor-driven", i.e., governed by the presolvation of H2O, and back to
acceptor-driven near the room-temperature solubility limit of 19 mol/L, which
corresponds to an extremely solvent-deficient system containing only about one
H2O molecule per ion. Specifically, we identify concentration ranges where the
proton transfer rate is mostly affected by OH(-) losing an accepted hydrogen
bond, OH(-) forming a donated hydrogen bond, H2O forming an accepted hydrogen
bond, or H2O losing a coordinated Na(+). Presolvation also manifests itself in
the shortening of the Na(+)-OH2 distances, in that the Na(+) "pushes" one of the
H2O protons away.
PMID- 27504987
TI - Phase-contrast MRI with hybrid one and two-sided flow-encoding and velocity
spectrum separation.
AB - PURPOSE: To develop and evaluate a phase-contrast MRI (PC-MRI) technique with
hybrid one and two-sided flow-encoding and velocity spectrum separation (HOTSPA)
for accelerated blood flow and velocity measurement. METHODS: In the HOTSPA
technique, the two-sided flow encoding (FE) is used for two FE directions and one
sided is used for the remaining FE direction. Such a temporal modulation of the
FE strategy allows for separations of the Fourier velocity spectrum into
components for the flow-compensated and the three-directional velocity waveforms,
accelerating PC-MRI by encoding three-directional velocities using only two
repetition times (TRs) instead of four TRs as in standard PC-MRI. The HOTSPA was
evaluated and compared with standard PC-MRI in the common carotid arteries of six
healthy volunteers. RESULTS: Total volumetric flow and peak velocity measurements
based on HOTSPA and the conventional PC-MRI were in good agreement with a bias of
-0.005 mL (-0.1% relative bias error) for total volumetric flow and 1.21 cm/s
(1.1% relative bias error) for peak velocity, although the total acquisition time
was 50% of the conventional PC-MRI. CONCLUSION: The proposed HOTSPA technique
achieved nearly two-fold acceleration of PC-MRI while maintaining accuracy for
total volumetric flow and peak velocity quantification by separating the paired
acquisitions in the Fourier velocity spectrum domain. Magn Reson Med 78:182-192,
2017. (c) 2016 International Society for Magnetic Resonance in Medicine.
PMID- 27504988
TI - Metal-Free Activation of a C(sp)-H Bond of Aryl Acetylenes.
AB - C(sp)-H Bond activation of acetylene molecule still remains a challenge for
synthetic organic chemists. In practice, acetylenes are activated by strong bases
and metals. The first example for activating acetylenic protons under base and
metal-free conditions is reported here. It involves a general method for
synthesizing propargylic derivatives of cotarnine. An array of
tetrahydroisoquinolines alkaloids was synthesized by C(sp)-H bond activation of
aromatic acetylenes with cotarnine at room temperature. A DFT-based mechanism is
proposed for the reaction.
PMID- 27504989
TI - The State-of-the-Science on Somatosensory Function and Its Impact on Daily Life
in Adults and Older Adults, and Following Stroke: A Scoping Review.
AB - The aim was to identify and synthesize research evidence about how adults and
older adults process somatosensory information in daily activities, and the
interventions available to regain somatosensory function following stroke. We
developed two interacting concept maps to address the research questions. The
scoping review was conducted from 2005 to 2015 across Web of Science, AMED,
CINAHL, Embase, Medline, and PsychInfo databases. Search terms included
somatosensory, perception, performance, participation, older adult, stroke,
intervention, discrimination, learning, and neuroplasticity. Contributions from
103 articles for Concept 1 and 14 articles for Concept 2 are reported. Measures
of somatosensory processing, performance, and participation used are identified.
Interventions available to treat somatosensory loss are summarized in relation to
approach, outcome measures, and theory/mechanisms underlying. A gap exists in the
current understanding of how somatosensory function affects the daily lives of
adults. A multidisciplinary approach that includes performance and participation
outcomes is recommended to advance the field.
PMID- 27504990
TI - The State of the Science on Sensory Factors and Their Impact on Daily Life for
Children: A Scoping Review.
AB - The objective of this study was to identify and synthesize research about how
sensory factors affect daily life of children. We designed a conceptual model to
guide a scoping review of research published from 2005 to October 2014 (10
years). We searched MEDLINE, CINAHL, and PsycINFO and included studies about
sensory perception/processing; children, adolescents/young adults; and
participation. We excluded studies about animals, adults, and review articles.
Our process resulted in 261 articles meeting criteria. Research shows that
children with conditions process sensory input differently than peers.
Neuroscience evidence supports the relationship between sensory-related behaviors
and brain activity. Studies suggest that sensory processing is linked to social
participation, cognition, temperament, and participation. Intervention research
illustrates the importance of contextually relevant practices. Future work can
examine the developmental course of sensory processing aspects of behavior across
the general population and focus on interventions that support children's sensory
processing as they participate in their daily lives.
PMID- 27504991
TI - (13)C or Not (13)C: Selective Synthesis of Asymmetric Carbon-13-Labeled
Platinum(II) cis-Acetylides.
AB - Asymmetric isotopic labeling of parallel and identical electron- or energy
transfer pathways in symmetrical molecular assemblies is an extremely challenging
task owing to the inherent lack of isotopic selectivity in conventional synthetic
methods. Yet, it would be a highly valuable tool in the study and control of
complex light-matter interactions in molecular systems by exclusively and
nonintrusively labeling one of otherwise identical reaction pathways, potentially
directing charge and energy transport along a chosen path. Here we describe the
first selective synthetic route to asymmetrically labeled organometallic
compounds, on the example of charge-transfer platinum(II) cis-acetylide
complexes. We demonstrate the selective (13)C labeling of one of two acetylide
groups. We further show that such isotopic labeling successfully decouples the
two nu(C=C) in the mid-IR region, permitting independent spectroscopic monitoring
of two otherwise identical electron-transfer pathways, along the (12)C=(12)C and
(13)C=(13)C coordinates. Quantum-mechanical mixing leads to intriguing complex
features in the vibrational spectra of such species, which we successfully model
by full-dimensional anharmonically corrected DFT calculations, despite the large
size of these systems. The synthetic route developed and demonstrated herein
should lead to a great diversity of asymmetric organometallic complexes
inaccessible otherwise, opening up a plethora of opportunities to advance the
fundamental understanding and control of light-matter interactions in molecular
systems.
PMID- 27504992
TI - Team Reading (Peer Review) of Suspicious/Positive Slides for Continuous Quality
Improvement in Cervical-Vaginal Cytology: A Comparison between Methods and
Indicators.
AB - AIM: In 2013, the Local Health Unit Roma 2 ex C screening laboratory introduced a
new set of indicators for quality assurance. We compare 2 sets of indicators
based on routine multiple readings (peer review) for their ability to identify
problems in single-reader accuracy. METHODS: All suspect slides were blindly
reviewed by all the cytologists of the laboratory. The standard set of indicators
includes interreader Cohen's kappa, positivity rate and atypical squamous cell of
undetermined significance/squamous intraepithelial lesion (ASC-US/SIL) ratio. The
new set included sensitivity for cervical intraepithelial neoplasia of grade 2 or
worse (CIN2+), positive predictive value (PPV) and percentage of positive high
risk (HR)-HPV cases among ASC-US. In order to estimate sensitivity and PPV, we
considered all women for whom there was a consensus of negative cytology,
negative HR-HPV test, negative colposcopy or negative histology true negative.
RESULTS: Kappa values ranged from 0.521 to 0.753, with narrow 95% confidence
intervals (CIs). Positivity rate ranged from 73.9 to 85.7 and the ASC-US/SIL
ratio from 0.61 to 0.81. Sensitivity for CIN2+ at the low-grade SIL threshold
ranged from 85.8 to 94.2, PPV ranged from 14.8 to 19.4, and both had a broad 95%
CI. Readers with low sensitivity did not show low kappa values. The percentage
proportion of HR-HPV-positives (HR-HPV+) among ASC-US ranged from 39.9 to 43.8%
with a narrow 95% CI. CONCLUSION: The proportion of HR-HPV+ among ASC-US cases is
a powerful indicator to address in training.
PMID- 27504993
TI - Laser, radiofrequency, and ethanol ablation for the management of thyroid
nodules.
AB - PURPOSE OF REVIEW: The majority of benign thyroid nodules are nearly
asymptomatic, remain stable in size, and do not require treatment. However, a
minority of patients with growing nodules may complain of local symptoms or have
cosmetic concerns, and thus seek surgical consultation. RECENT FINDINGS: The
timely use of ultrasound-guided minimally invasive procedures can change the
natural history of benign enlarging thyroid nodules. The procedures produce
persistent shrinkage of thyroid nodules and are associated with improvement of
local symptoms. Among the various procedures, percutaneous ethanol injection
represents the first-line treatment for relapsing thyroid cysts. In solid
nonfunctioning nodules, laser and radiofrequency ablation produces a more than
50% reduction in nodular volume that remains persistent over several years. For
hyperfunctioning nodules, thermal ablation techniques are not appropriate unless
radioactive iodine is contraindicated or not accessible. SUMMARY: MITs are best
suited for the management of medium or large-sized nodules that are
sonographically well visualized. Conversely, large nodules or nodular goiters
that extend into the chest are difficult to treat. MITs are performed in
outpatient clinics, are less expensive, and have a lower risk of complications,
compared to surgery, and usually do not induce thyroid dysfunction. However,
malignancy should be ruled out with a dedicated ultrasound neck assessment and
repeat fine needle aspiration of the lesion before treatment.
PMID- 27504994
TI - Dispersion and Hydrogen Bonding Rule: Why the Vaporization Enthalpies of Aprotic
Ionic Liquids Are Significantly Larger than those of Protic Ionic liquids.
AB - It is well known that gas-phase experiments and computational methods point to
the dominance of dispersion forces in the molecular association of hydrocarbons.
Estimates or even quantification of these weak forces are complicated due to
solvent effects in solution. The dissection of interaction energies and
quantification of dispersion interactions is particularly challenging for polar
systems such as ionic liquids (ILs) which are characterized by a subtle balance
between Coulomb interactions, hydrogen bonding, and dispersion forces. Here, we
have used vaporization enthalpies, far-infrared spectroscopy, and dispersion
corrected calculations to dissect the interaction energies between cations and
anions in aprotic (AILs), and protic (PILs) ionic liquids. It was found that the
higher total interaction energy in PILs results from the strong and directional
hydrogen bonds between cation and anion, whereas the larger vaporization
enthalpies of AILs clearly arise from increasing dispersion forces between ion
pairs.
PMID- 27504995
TI - Light/dark cycle of microalgae cells in raceway ponds: Effects of paddlewheel
rotational speeds and baffles installation.
AB - The aim of this work was to study the light/dark (L/D) cycle in raceway ponds
(RWPs) by the computational fluid dynamics (CFD) method via determining the
hydrodynamics of culture media and cell trajectories. The effects of paddlewheel
rotational speed and flow-deflector baffles installation on the L/D cycle were
analyzed. The results indicated that, the L/D cycles of microalgae cells
decreased with the increase of the paddlewheel rotational speeds, when the
paddlewheel rotational speeds ranged from 5 to 12rpm. In addition, the
installation of the flow-deflector baffles in RWPs can greatly increase the light
time and the ratio of light time to L/D cycle for microalgae cells. The study
provided an effective method to characterize the L/D cycles in RWPs, and may have
important implications for designing the effective large-scale microalgae culture
system.
PMID- 27504996
TI - Recently characterized molecular events in uncommon gynaecological neoplasms and
their clinical importance.
AB - The introduction of new sequencing technologies has resulted in the discovery of
commonly mutated genes in uncommon cancers, including non-epithelial ovarian
neoplasms and other rare gynaecological tumours, such as cervical embryonal
rhabdomyosarcoma. In some of these neoplasms, mutations in certain genes are both
frequent and specific enough for the genomic mutations and sometimes their
associated protein loss or overexpression to be used as an aid to diagnosis. In
this review, we contrast previous gene identification methods with newer ones,
and discuss how the new sequencing technologies (collectively referred to as
'next-generation sequencing') have permitted the identification of specific
molecular events that characterize several rare gynaecological neoplasms. We
highlight the value of using sequencing to complement traditional pathological
methods when diagnosing certain tumours, and provide practical advice to
pathologists dealing with these neoplasms. We focus on adult granulosa cell
tumours (somatic monoallelic mutations in FOXL2), Sertoli-Leydig cell tumours,
gynaecological embryonal rhabdomyosarcomas (germline and somatic mutations in
DICER1), and small-cell carcinoma of the ovary, hypercalcaemic type (biallelic
mutations in SMARCA4). The new genetic findings provided by next-generation
sequencing in these uncommon neoplasms have brought these disorders back into
focus, and point the way towards new diagnostic, preventive and therapeutic
avenues.
PMID- 27504997
TI - 3 Tesla-Diffusion Tensor Imaging in Autosomal Dominant Polycystic Kidney Disease:
The Nephrologist's Point of View.
AB - BACKGROUND/AIMS: CT, MRI and ultrasound are currently used for screening and
follow-up of individuals affected by autosomal dominant polycystic kidney disease
(ADPKD). Dynamic contrast-enhanced MRI studies renal perfusion after gadolinium
administration, with possible side effects, such as nephrogenic systemic
fibrosis. The aim of our study was to evaluate the clinical application of 3
Tesla (3T)-diffusion tensor image (DTI) in ADPKD patients, correlating its
parameters, such as fractional anisotropy (FA), and apparent diffusion
coefficient (ADC) with kidney function tests. METHODS: Eight ADPKD patients and 6
healthy volunteers (HS) were enrolled. FA and ADC mean values were calculated.
And correlations between DTI-parameters, creatinine and estimated glomerular
filtration rate (eGFR) were evaluated. RESULTS: Parenchymal FA was significantly
lower in ADPKD than HS (FA: 0.17 +/- 0.03 vs. 0.22 +/- 0.01; p = 0.02), whereas
parenchymal ADC was higher in patients than controls (2.48 (*10-3) +/- 0.16 vs.
2.28 (*10-3) +/- 0.09), but a statistically significant difference was not
achieved (p = 0.27). Direct correlations were revealed between eGFR and FA (r =
0.82; p = 0.0003), whereas an inverse correlation was found with creatinine (r =
0.77; p = 0.001). Similarly, ADC closely correlated with creatinine (r = 0.79; p
= 0.0006) and eGFR (r = -0.620; p = 0.01). CONCLUSION: 3T-DTI is a promising
radiological tool that could be used by nephrologists to evaluate ADPKD patients,
highlighting early micro-structure alterations, without side effects and contrast
agent administration.
PMID- 27504998
TI - The Urinary Phosphate to Serum Fibroblast Growth Factor 23 Ratio Is a Useful
Marker of Atherosclerosis in Early-Stage Chronic Kidney Disease.
AB - BACKGROUND: Fibroblast growth factor 23 (FGF23) regulates mineral homeostasis. In
developed renal dysfunction, FGF23 levels increase to maintain the phosphate
excretion capacity. However, in diabetic patients with early-stage renal
impairment, the FGF23 elevation is not very sensitive. We hypothesized that
urinary phosphate (U-P)/serum FGF23 ratio would theoretically be an index that
reflects the number of nephrons (nephron index). In this study, we determined
whether the nephron index would be associated with renal function and vascular
diseases in diabetic patients. METHODS: In total, 142 patients with diabetes
mellitus were enrolled. The nephron index was calculated using the following
formula: U-P (mg/day)/ serum FGF23 (pg/ml). RESULTS: The mean age was 63 +/- 11
years and eGFR levels were 79.5 +/- 25.4 ml/min/1.73 m2, respectively. Thirty
patients had a medical history of macroangiopathy. The Nephron index was
significantly decreased in subjects with macroangiopathy compared with those
without macroangiopathy. A multivariate analysis of risk factors for
macroangiopathy revealed that duration of diabetes, eGFR, and nephron index were
significantly associated with a higher frequency of arteriosclerotic disease.
CONCLUSION: These findings suggest that a decrease in nephron index reflects
early-stage renal impairment and is an independent risk factor of macroangiopathy
in diabetic patients.
PMID- 27505000
TI - An Inverse Method to Estimate the Root Water Uptake Source-Sink Term in Soil
Water Transport Equation under the Effect of Superabsorbent Polymer.
AB - The widespread use of superabsorbent polymers (SAPs) in arid regions improves the
efficiency of local land and water use. However, SAPs' repeated absorption and
release of water has periodic and unstable effects on both soil's physical and
chemical properties and on the growth of plant roots, which complicates modeling
of water movement in SAP-treated soils. In this paper, we proposea model of soil
water movement for SAP-treated soils. The residence time of SAP in the soil and
the duration of the experiment were considered as the same parameter t. This
simplifies previously proposed models in which the residence time of SAP in the
soil and the experiment's duration were considered as two independent parameters.
Numerical testing was carried out on the inverse method of estimating the
source/sink term of root water uptake in the model of soil water movement under
the effect of SAP. The test results show that time interval, hydraulic
parameters, test error, and instrument precision had a significant influence on
the stability of the inverse method, while time step, layering of soil, and
boundary conditions had relatively smaller effects. A comprehensive analysis of
the method's stability, calculation, and accuracy suggests that the proposed
inverse method applies if the following conditions are satisfied: the time
interval is between 5 d and 17 d; the time step is between 1000 and 10000; the
test error is >= 0.9; the instrument precision is <= 0.03; and the rate of soil
surface evaporation is <= 0.6 mm/d.
PMID- 27504999
TI - Hepatocarcinogenesis associated with hepatitis B, delta and C viruses.
AB - Globally, over half a billion people are persistently infected with hepatitis B
(HBV) and/or hepatitis C viruses. Chronic HBV and HCV infection frequently lead
to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Co-infections with
hepatitis delta virus (HDV), a subviral satellite requiring HBV for its
propagation, accelerates the progression of liver disease toward HCC. The
mechanisms by which these viruses cause malignant transformation, culminating in
HCC, remain incompletely understood, partially due to the lack of adequate
experimental models for dissecting these complex disease processes in vivo.
PMID- 27505001
TI - Comparative Genomics Analysis of Streptococcus tigurinus Strains Identifies
Genetic Elements Specifically and Uniquely Present in Highly Virulent Strains.
AB - Streptococcus tigurinus is responsible for severe invasive infections such as
infective endocarditis, spondylodiscitis and meningitis. As described, S.
tigurinus isolates AZ_3aT and AZ_14 were highly virulent (HV phenotype) in an
experimental model of infective endocarditis and showed enhanced adherence and
invasion of human endothelial cells when compared to low virulent S. tigurinus
isolate AZ_8 (LV phenotype). Here, we sought whether genetic determinants could
explain the higher virulence of AZ_3aT and AZ_14 isolates. Several genetic
determinants specific to the HV strains were identified through extensive
comparative genomics amongst which some were thought to be highly relevant for
the observed HV phenotype. These included i) an iron uptake and metabolism
operon, ii) an ascorbate assimilation operon, iii) a newly acquired PI-2-like
pilus islets described for the first time in S. tigurinus, iv) a hyaluronate
metabolism operon, v) an Entner-Doudoroff pathway of carbohydrates metabolism,
and vi) an alternate pathways for indole biosynthesis. We believe that the
identified genomic features could largely explain the phenotype of high
infectivity of the two HV S. tigurinus strains. Indeed, these features include
determinants that could be involved at different stages of the disease such as
survival of S. tigurinus in blood (iron uptake and ascorbate metabolism operons),
initial attachment of bacterial pathogen to the damaged cardiac tissue and/or
vegetation that formed on site (PI-2-like pilus islets), tissue invasion
(hyaluronate operon and Entner-Doudoroff pathway) and regulation of pathogenicity
(indole biosynthesis pathway).
PMID- 27505002
TI - Zika Virus, a New Threat for Europe?
AB - BACKGROUND: Since its emergence in 2007 in Micronesia and Polynesia, the
arthropod-borne flavivirus Zika virus (ZIKV) has spread in the Americas and the
Caribbean, following first detection in Brazil in May 2015. The risk of ZIKV
emergence in Europe increases as imported cases are repeatedly reported. Together
with chikungunya virus (CHIKV) and dengue virus (DENV), ZIKV is transmitted by
Aedes mosquitoes. Any countries where these mosquitoes are present could be
potential sites for future ZIKV outbreak. We assessed the vector competence of
European Aedes mosquitoes (Aedes aegypti and Aedes albopictus) for the currently
circulating Asian genotype of ZIKV. METHODOLOGY/PRINCIPAL FINDINGS: Two
populations of Ae. aegypti from the island of Madeira (Funchal and Paul do Mar)
and two populations of Ae. albopictus from France (Nice and Bar-sur-Loup) were
challenged with an Asian genotype of ZIKV isolated from a patient in April 2014
in New Caledonia. Fully engorged mosquitoes were then maintained in insectary
conditions (28 degrees +/-1 degrees C, 16h:8h light:dark cycle and 80% humidity).
16-24 mosquitoes from each population were examined at 3, 6, 9 and 14 days post
infection to estimate the infection rate, disseminated infection rate and
transmission efficiency. Based on these experimental infections, we demonstrated
that Ae. albopictus from France were not very susceptible to ZIKV.
CONCLUSIONS/SIGNIFICANCE: In combination with the restricted distribution of
European Ae. albopictus, our results on vector competence corroborate the low
risk for ZIKV to expand into most parts of Europe with the possible exception of
the warmest regions bordering the Mediterranean coastline.
PMID- 27505003
TI - Correction: Advance Care Planning in Dementia: Do Family Carers Know the
Treatment Preferences of People with Early Dementia?
AB - [This corrects the article DOI: 10.1371/journal.pone.0159056.].
PMID- 27505004
TI - Cyclin-Dependent Kinase 14 Promotes Cell Proliferation, Migration and Invasion in
Ovarian Cancer by Inhibiting Wnt Signaling Pathway.
AB - OBJECTIVE: The study aimed to investigate cyclin-dependent kinase 14 (CDK14) and
its co-function with Wnt signaling pathway on cell proliferation, migration and
invasion in ovarian cancer. METHODS: CDK14 expressions were detected by
quantitative real-time polymerase chain reaction. The expressions c-Myc,
cyclinD1, PFTK1, ki67 and OGT were examined by Western blot. MTT assay was
applied to observe cell proliferation after transfection of pEGFP-N1/CDK14-siRNA
and pEGFP-N1 into SKOV3 cells, and scratch test and Transwell assay to observe
invasion and migration ability. Transfected tumor model in nude mice was
established. RESULTS: CDK14 was upregulated in the ovarian cancer tissues and
cell lines (both p < 0.05). Expressions of downstream molecules in Wnt signaling
pathway as well as the proliferation, invasion and migration ability of the SKOV3
cells were reduced when CDK14 was inhibited (all p < 0.05). The expression of
beta-catenin in the nucleus was also decreased when CDK14 was inhibited (p <
0.05). In the transfected tumor model of nude mice, the results showed, compared
with the pEGFP-N1 group and blank control group, that the expressions of c-Myc,
cyclinD1, PFTK1, ki67 and OGT in the pEGFP-N1/CDK14-siRNA group in the
transplantation tumor tissues decreased significantly (all p < 0.05). CONCLUSION:
CDK14 suppression-mediated Wnt signaling pathway can inhibit cell proliferation,
invasion and migration in ovarian cancer.
PMID- 27505005
TI - Vaccine Potential and Diversity of the Putative Cell Binding Factor (CBF,
NMB0345/NEIS1825) Protein of Neisseria meningitidis.
AB - The cbf gene from Neisseria meningitidis strain MC58 encoding the putative Cell
Binding Factor (CBF, NMB0345/NEIS1825) protein was cloned into the pRSETA system
and a ~36-kDa recombinant (r)CBF protein expressed in Escherichia coli and
purified by metal affinity chromatography. High titres of rCBF antibodies were
induced in mice following immunization with rCBF-saline, rCBF-Al(OH)3, rCBF
Liposomes or rCBF-Zwittergent (Zw) 3-14 micelles, both with and without
incorporated monophosphoryl lipid A (MPLA) adjuvant. Anti-rCBF sera reacted in
western blots of meningococcal lysates with a single protein band of molecular
mass ~29.5 kDa, indicative of mature CBF protein, but did not react with a lysate
of a Deltanmb0345 mutant (CBF-), demonstrating specificity of the murine immune
responses. CBF protein was produced by all strains of meningococci studied thus
far and the protein was present on the surface of MC58 (CBF+) bacteria, but
absent on Deltanmb0345 mutant (CBF-) bacteria, as judged by FACS reactivity of
anti-rCBF sera. Analysis of the NEIS1825 amino acid sequences from 6644 N.
meningitidis isolates with defined Alleles in the pubmlst.org/Neisseria database
showed that there were 141 ST types represented and there were 136 different
allelic loci encoding 49 non-redundant protein sequences. Only 6/6644 (<0.1%) of
N. meningitidis isolates lacked the nmb0345 gene. Amongst serogroup B isolates
worldwide, ~68% and ~20% expressed CBF encoded by Allele 1 and 18 respectively,
with the proteins sharing >99% amino acid identity. Murine antisera to rCBF in Zw
3-14 micelles + MPLA induced significant serum bactericidal activity (SBA)
against homologous Allele 1 and heterologous Allele 18 strains, using both baby
rabbit serum complement and human serum complement (h)SBA assays, but did not
kill strains expressing heterologous protein encoded by Alelle 2 or 3.
Furthermore, variable bactericidal activity was induced by murine antisera
against different meningococcal strains in the hSBA assay, which may correlate
with variable surface exposure of CBF. Regardless, the attributes of amino acid
sequence conservation and protein expression amongst different strains and the
ability to induce cross-strain bactericidal antibodies indicates that rCBF could
be a potential meningococcal vaccine antigen and merits further testing.
PMID- 27505006
TI - Diagnosis and outcome of Clostridium difficile infection by toxin enzyme
immunoassay and polymerase chain reaction in an island population.
AB - BACKGROUND AND AIM: Clostridium difficile infection (CDI) is a potentially life
threatening cause of diarrhea. Correct laboratory diagnosis is essential to
differentiate CDI from other causes of diarrhea. A positive fecal C. difficile
toxin (CDT) is the best indicator of CDI, but the significance of a positive
fecal nucleic acid amplification test (NAAT) remains unclear. Our aim was to
elucidate the significance of CDI diagnostics in patients in Jersey. METHODS: A
retrospective, 5-year study was conducted at an island district general hospital
of patients who developed CDI. Patients were grouped according to CDT and NAAT
status and their association with outcome (indicators of severity and 30-day case
fatality rate) compared. RESULTS: A total of 207 specimens were toxin positive,
92 NAAT positive and toxin negative, and 39 had a stool sample negative by both
toxin and NAAT testing. A positive toxin stool sample was associated with both
significantly higher white cell count (14.5 * 109 /L vs 11.3 * 109 /L, P = 0.003)
and C-reactive protein (114.7 mg/dL vs 82.9 mg/dL, P = 0.001), but NAAT
positivity was not (P = 0.269, 0.728). A positive CDT assay was a significant
independent predictor of death (odds ratio [OR]: 1.89 [95% CI: 1.04-3.43], P =
0.046), but a positive NAAT in CDT negative samples was not (OR: 1.02 [95% CI:
0.34-3.12], P = 1.0). CONCLUSIONS: The findings of this study, derived from
evolving clinical practice, provide greater clarity in the interpretation of CDI
diagnostics. In CDT-negative disease, a positive NAAT neither predicts disease
severity nor mortality. NAAT-positive and toxin-negative patients require
instigation of infection control measures, but the need for specific treatment
remains unclear.
PMID- 27505007
TI - Effect of Chemical Charging/Discharging on Plasmonic Behavior of Silver Metal
Nanoparticles Prepared using Citrate-Stabilized Cadmium Selenide Quantum Dots.
AB - The thermodynamics and kinetics of the chemical and electrochemical charging of a
catalyst surface are very important to understand its applicability as a catalyst
material, particularly in redox catalysis. Through the present study, we hereby
communicate the results obtained from our detailed investigations related to the
effect of chemical charging on the plasmonic behavior of silver metal
nanoparticles (Ag MNPs) as redox catalysts. Two different batches of Ag MNPs were
prepared through thermally assisted chemical reduction of silver ions. The
difference in these batches was the use or not of citrate-capped cadmium selenide
quantum dots (Q-CdSe) for the reduction of solution-phase silver ions to their
colloidal plasmonic phase. The charge on the surfaces of the Ag MNPs was varied
by the chemical electron injection method by using BH4- ions from a NaBH4
solution. The processes of charging and discharging were monitored by using
UV/Vis absorption spectroscopy. The impact of the concentration of the reductant
on the charging and discharging processes was also investigated. The Ag MNPs were
also tested for their voltammetric response, wherein it was observed that it was
more difficult to oxidize the Ag MNPs prepared with Q-CdSe seeds than to oxidize
Ag MNPs prepared without Q-CdSe particles. Our results demonstrate that Q-CdSe
seeds not only enhance the redox catalytic activity of Ag MNPs but also provide
stability towards polarization of their plasmonic behavior.
PMID- 27505008
TI - Molecular Paleoclimate Reconstructions over the Last 9 ka from a Peat Sequence in
South China.
AB - To achieve a better understanding of Holocene climate change in the monsoon
regions of China, we investigated the molecular distributions and carbon and
hydrogen isotope compositions (delta13C and deltaD values) of long-chain n
alkanes in a peat core from the Shiwangutian (SWGT) peatland, south China over
the last 9 ka. By comparisons with other climate records, we found that the
delta13C values of the long-chain n-alkanes can be a proxy for humidity, while
the deltaD values of the long-chain n-alkanes primarily recorded the moisture
source deltaD signal during 9-1.8 ka BP and responded to the dry climate during
1.8-0.3 ka BP. Together with the average chain length (ACL) and the carbon
preference index (CPI) data, the climate evolution over last 9 ka in the SWGT
peatland can be divided into three stages. During the first stage (9-5 ka BP),
the delta13C values were depleted and CPI and Paq values were low, while ACL
values were high. They reveal a period of warm and wet climate, which is regarded
as the Holocene optimum. The second stage (5-1.8 ka BP) witnessed a shift to
relatively cool and dry climate, as indicated by the more positive delta13C
values and lower ACL values. During the third stage (1.8-0.3 ka BP), the
delta13C, deltaD, CPI and Paq values showed marked increase and ACL values varied
greatly, implying an abrupt change to cold and dry conditions. This climate
pattern corresponds to the broad decline in Asian monsoon intensity through the
latter part of the Holocene. Our results do not support a later Holocene optimum
in south China as suggested by previous studies.
PMID- 27505009
TI - Genetic Structure in a Small Pelagic Fish Coincides with a Marine Protected Area:
Seascape Genetics in Patagonian Fjords.
AB - Marine environmental variables can play an important role in promoting population
genetic differentiation in marine organisms. Although fjord ecosystems have
attracted much attention due to the great oscillation of environmental variables
that produce heterogeneous habitats, species inhabiting this kind of ecosystem
have received less attention. In this study, we used Sprattus fuegensis, a small
pelagic species that populates the inner waters of the continental shelf,
channels and fjords of Chilean Patagonia and Argentina, as a model species to
test whether environmental variables of fjords relate to population genetic
structure. A total of 282 individuals were analyzed from Chilean Patagonia with
eight microsatellite loci. Bayesian and non-Bayesian analyses were conducted to
describe the genetic variability of S. fuegensis and whether it shows spatial
genetic structure. Results showed two well-differentiated genetic clusters along
the Chilean Patagonia distribution (i.e. inside the embayment area called TicToc,
and the rest of the fjords), but no spatial isolation by distance (IBD) pattern
was found with a Mantel test analysis. Temperature and nitrate were correlated to
the expected heterozygosities and explained the allelic frequency variation of
data in the redundancy analyses. These results suggest that the singular genetic
differences found in S. fuegensis from inside TicToc Bay (East of the Corcovado
Gulf) are the result of larvae retention bya combination of oceanographic
mesoscale processes (i.e. the west wind drift current reaches the continental
shelf exactly in this zone), and the local geographical configuration (i.e.
embayment area, islands, archipelagos). We propose that these features generated
an isolated area in the Patagonian fjords that promoted genetic differentiation
by drift and a singular biodiversity, adding support to the existence of the
largest marine protected area (MPA) of continental Chile, which is the Tic-Toc
MPA.
PMID- 27505010
TI - Renal Autotransplantation at Three Academic Institutions in Turkey.
AB - OBJECTIVE: The objective of this study is to present the experience of 3
institutions performing renal autotransplantation (RAT) and to discuss surgical
techniques employed and the results in the light of the medical literature.
MATERIALS AND METHODS: A total of 14 patients (11 male and 3 female) with a mean
age of 47 +/- 8 years (35-61 years), who underwent RAT procedure at 3 different
institutions between October 2006 and November 2014, in Turkey, were evaluated
retrospectively. Indications for RAT procedure are ureteral avulsion, renal
artery aneurysm and intimal dissection caused by percutaneous transluminal renal
artery angioplasty (PTRA). Twelve patients with ureteral avulsion, 1 patient with
renal artery aneurysm and 1 patient with intimal dissection caused by PTRA were
followed-up for 103 months. Seven (50%) open and 7 (50%) laparoscopic
nephrectomies were performed. Nine patients (64.3%) were right-sided and 5
patients (35.7%) were left-sided. Complications of grade III and above as per
Clavien-Dindo classification were assessed. RESULTS: Mean time from injury to RAT
was 21.2 +/- 40.1 days. However, 5 (35.7%) patients were treated on the same day
of the injury. As per Clavien-Dindo classification, 2 (14.2%) grade IVa and 1
(7.1%) grade IIIa complications were reported. However, no significant
correlation was observed between the complications and graft loss regarding type
and side of the nephrectomy performed (p = 0.462 and p = 0.505, respectively) and
timing of the intervention (p = 0.692). CONCLUSION: RAT is a safe procedure in
combination with minimally invasive laparoscopic technique in carefully selected
patients; however, it requires expertise and proficiency in laparoscopy,
reconstructive urology and transplantation. Nevertheless RAT should be considered
as the last resort, when other modalities fail.
PMID- 27505011
TI - Effects of walking in deep venous thrombosis: a new integrated solid and fluid
mechanics model.
AB - Deep venous thrombosis (DVT) is a common disease. Large thrombi in venous vessels
cause bad blood circulation and pain; and when a blood clot detaches from a vein
wall, it causes an embolism whose consequences range from mild to fatal. Walking
is recommended to DVT patients as a therapeutical complement. In this study the
mechanical effects of walking on a specific patient of DVT were simulated by
means of an unprecedented integration of 3 elements: a real geometry, a
biomechanical model of body tissues, and a computational fluid dynamics study. A
set of computed tomography images of a patient's leg with a thrombus in the
popliteal vein was employed to reconstruct a geometry model. Then a biomechanical
model was used to compute the new deformed geometry of the vein as a function of
the fiber stretch level of the semimembranosus muscle. Finally, a computational
fluid dynamics study was performed to compute the blood flow and the wall shear
stress (WSS) at the vein and thrombus walls. Calculations showed that either a
lengthening or shortening of the semimembranosus muscle led to a decrease of WSS
levels up to 10%. Notwithstanding, changes in blood viscosity properties or blood
flow rate may easily have a greater impact in WSS.
PMID- 27505012
TI - Understanding Alzheimer's disease and the aging brain: An Interview with Dr.
Christopher van Dyck.
PMID- 27505013
TI - Amyloid-beta Alzheimer targets - protein processing, lipid rafts, and amyloid
beta pores.
AB - Amyloid beta (Abeta), the hallmark of Alzheimer's Disease (AD), now appears to be
deleterious in its low number aggregate form as opposed to the macroscopic Abeta
fibers historically seen postmortem. While Alzheimer targets, such as the tau
protein, amyloid precursor protein (APP) processing, and immune system activation
continue to be investigated, the recent discovery that amyloid beta aggregates at
lipid rafts and likely forms neurotoxic pores has led to a new paradigm regarding
why past therapeutics may have failed and how to design the next round of
compounds for clinical trials. An atomic resolution understanding of Abeta
aggregates, which appear to exist in multiple conformations, is most desirable
for future therapeutic development. The investigative difficulties, structures of
these small Abeta aggregates, and current therapeutics are summarized in this
review.
PMID- 27505014
TI - Neural stem/progenitor cells in Alzheimer's disease.
AB - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and a
worldwide health challenge. Different therapeutic approaches are being developed
to reverse or slow the loss of affected neurons. Another plausible therapeutic
way that may complement the studies is to increase the survival of existing
neurons by mobilizing the existing neural stem/progenitor cells (NSPCs) - i.e.
"induce their plasticity" - to regenerate lost neurons despite the existing
pathology and unfavorable environment. However, there is controversy about how
NSPCs are affected by the unfavorable toxic environment during AD. In this
review, we will discuss the use of stem cells in neurodegenerative diseases and
in particular how NSPCs affect the AD pathology and how neurodegeneration affects
NSPCs. In the end of this review, we will discuss how zebrafish as a useful model
organism with extensive regenerative ability in the brain might help to address
the molecular programs needed for NSPCs to respond to neurodegeneration by
enhanced neurogenesis.
PMID- 27505015
TI - Side effects of a dopamine agonist therapy for Parkinson's disease: a mini-review
of clinical pharmacology.
AB - Dopamine agonists (DA) are therapeutic agents that are commonly used in the
treatment of Parkinson's disease (PD). They can reduce undesired motor
fluctuations and delay the administration of levodopa therapy. However, this drug
family is associated with specific side effects that can significantly diminish
the quality of life among PD patients. Some of them impose significant risks for
individuals who have a history of cardiovascular diseases, psychosis, and
depression, or those older patients who suffer from renal or hepatic
insufficiency. Various pharmacokinetic and pharmacodynamic considerations need to
be taken into account when administering DA therapy. The goal of this review is
to provide a comprehensive, up-to-date overview of DA therapeutic modalities for
PD.
PMID- 27505016
TI - The Significance of the Default Mode Network (DMN) in Neurological and
Neuropsychiatric Disorders: A Review.
AB - The relationship of cortical structure and specific neuronal circuitry to global
brain function, particularly its perturbations related to the development and
progression of neuropathology, is an area of great interest in neurobehavioral
science. Disruption of these neural networks can be associated with a wide range
of neurological and neuropsychiatric disorders. Herein we review activity of the
Default Mode Network (DMN) in neurological and neuropsychiatric disorders,
including Alzheimer's disease, Parkinson's disease, Epilepsy (Temporal Lobe
Epilepsy - TLE), attention deficit hyperactivity disorder (ADHD), and mood
disorders. We discuss the implications of DMN disruptions and their relationship
to the neurocognitive model of each disease entity, the utility of DMN assessment
in clinical evaluation, and the changes of the DMN following treatment.
PMID- 27505018
TI - Neurodegeneration and Neuroprotection in Glaucoma.
AB - Glaucoma is the principal cause of irreversible blindness in the world. The
disease leads to progressive optic nerve degeneration with a gradual loss of
retinal ganglion cells. Neurodegeneration in glaucoma extends beyond the eye into
the lateral geniculate nucleus and visual cortex, and the disease even shares
some characteristics with other central nervous system degenerative disorders.
Glaucoma destroys neurons through oxidative stress, impairment in axonal
transport, neuroinflammation, and excitotoxicity. Autophagy may promote or
inhibit disease progression. Currently, lowering intraocular pressure is the only
way proven to delay glaucoma advancement. However, many new therapies are being
developed, including antioxidants, adenosine receptor antagonists, Rho-pathway
inhibitors, stem cell therapy, and neurotrophic factors. These therapies focus on
neuroprotection, and they may eventually halt glaucoma progression or reverse the
process of the disease itself.
PMID- 27505017
TI - Neurocardiovascular Instability and Cognition.
AB - Neurocardiovascular instability (NCVI) refers to abnormal neural control of the
cardiovascular system affecting blood pressure and heart rate behavior. Autonomic
dysfunction and impaired cerebral autoregulation in aging contribute to this
phenomenon characterized by hypotension and bradyarrhythmia. Ultimately, this
increases the risk of falls and syncope in older people. NCVI is common in
patients with neurodegenerative disorders including dementia. This review
discusses the various syndromes that characterize NCVI icluding hypotension,
carotid sinus hypersensitivity, postprandial hypotension and vasovagal syncope
and how they may contribute to the aetiology of cognitive decline. Conversely,
they may also be a consequence of a common neurodegenerative process. Regardless,
recognition of their association is paramount in optimizing management of these
patients.
PMID- 27505019
TI - Cross-education of strength and skill: an old idea with applications in the aging
nervous system.
AB - Edward Wheeler Scripture's 1894 work out of the Yale Psychological Laboratory has
been influential in identifying the nervous system's contribution to the
bilateral improvements that are seen with unilateral strength and skill training.
Scripture coined the term "cross-education" to describe this improvement in the
untrained contralateral limb. While physiological changes accompany aging that
may negatively affect the performance of physical tasks, far too much credit has
been given to the natural aging process rather than the effects of inactivity.
Emerging evidence indicates strength or skill training interventions induce
significant neuroplasticity in an aging population. The model of unilateral
training provides a unique approach in which to elicit such plasticity. This
brief review highlights the innate ability of the nervous system to adapt to
unilateral strength and skill training interventions, regardless of age, and
provides a novel perspective on the robust plastic ability of the aging nervous
system.
PMID- 27505020
TI - Social capital, health, and elderly driver status.
AB - Driving a car enables many people to engage in meaningful activities that, in
turn, help develop and maintain personal social capital. Social capital, a
combination of community participation and social cohesion, is important in
maintaining well-being. This paper argues that social capital can provide a
framework for investigating the general role of transportation and driving a car
specifically to access activities that contribute to connectedness and well-being
among older people. This paper proposes theoretically plausible and empirically
testable hypotheses about the relationship between driver status, social capital,
and well-being. A longitudinal study may provide a new way of understanding, and
thus of addressing, the well-being challenges that occur when older people
experience restrictions to, or loss of, their driver's license.
PMID- 27505021
TI - The Knowledge of Memory Aging Questionnaire: Factor Structure and Correlates in a
Lifespan Sample.
AB - The authors examined the factor structure of the Knowledge of Memory Aging
Questionnaire (KMAQ) [1] using confirmatory factor analysis in a lifespan sample
of 933 individuals who ranged in age from 18 to 101. Participants were college
students at Louisiana State University and adults from the community enrolled in
the Louisiana Healthy Aging Study (LHAS). A two-factor solution was expected,
consistent with the normal and pathological memory aging dimensions that comprise
the KMAQ. A bi-factor solution with items loading on a general response bias
factor and either a normal or pathological knowledge-specific factor showed good
model fit. Knowledge scores were correlated with demographic and cognitive
performance variables. Implications of these data for clinical settings and
research are considered.
PMID- 27505022
TI - Substance Misuse Education for Physicians: Why Older People are Important.
AB - This perspective article focuses on the need for training and education for
undergraduate medical students on substance-related disorders, and describes
initiatives undertaken in the United Kingdom (UK), Netherlands, United States
(US), and Norway to develop the skills, knowledge, and attitudes needed by future
doctors to treat patients adequately. In addition, we stress that in postgraduate
training, further steps should be taken to develop Addiction Medicine as a
specialized and transverse medical domain. Alcohol use disorder is a growing
public health problem in the geriatric population, and one that is likely to
continue to increase as the baby boomer generation ages. Prescription drug misuse
is a major concern, and nicotine misuse remains problematic in a substantial
minority. Thus, Addiction Medicine training should address the problems for this
specific population. In recent years, several countries have started an Addiction
Medicine specialty. Although addiction psychiatry has been a subspecialty in the
UK and US for more than 20 years, in most countries it has been a more recent
development. Additional courses on addiction should be integrated into the
curriculum at both undergraduate and postgraduate levels, as well as form part of
the continuous training of other medical specialists. It is recommended that
further research and mapping of what is currently taught in medical programs be
undertaken, so as to enhance medical education in addiction and improve treatment
services.
PMID- 27505023
TI - Palliative Care and the Humanities: Centralizing the Patient at the End of Life.
AB - Palliative care is a quickly growing facet of modern medicine. While scientific
advancements have broken new ground for the possibilities of end-of-life care,
sensitive treatment of the patient as an individual has lagged behind and has
frequently led to an unsatisfactory experience for patients, families, and the
medical community at large. This essay argues that centralizing patients during
the terminal phases of treatment by using humanistic perspectives has the
potential to bring new meaning and improved effectiveness to patients and
physicians alike.
PMID- 27505024
TI - Inhibiting the Self-Sorting Behavior in the Blends of a Homologous Set of
Polyurethane Model Compounds.
AB - Self-sorting is the phenomenon in which there is high fidelity recognition and
preference only for self and avoidance of nonself (narcissistic self-sorting). It
has been observed in a number of biological systems and chiral synthetic
molecules. We found that blends of biscarbamates, which are model compounds for
polyurethanes, self-sort during crystallization [ J. Phys. Chem. B 2008 , 112 ,
4223 - 4232 ], although these are not chiral molecules. Even if the two
components in the blend differ only by a couple of CH2 groups in the side chain
length, no intercomponent hydrogen bond forms, and the molecules self-sort. They
do not show any cocrystallization despite being part of a homologous series. We
believe that it is the first reported example such behavior among synthetic
nonchiral molecules. This is similar to the behavior of blends of hydrogen
bonding polymers including polyurethanes. We show that the difference in the
growth rates of the individual species is responsible for the self-sorting
behavior in these nonchiral synthetic compounds. While self-sorting might be
advantageous for separation of blends, it poses a challenge for modifying
properties such as the melting temperatures, spherulite size, etc., for various
applications. We will discuss methods that were attempted to bridge the self and
nonself that would lead to a more homogeneous system. We evaluated the
miscibility using differential scanning calorimetry (DSC), since the occurrence
of a single or multiple endotherms would indicate molecular level miscibility.
This is similar to the behavior of glass transition temperatures in the case of
polymer blends. Optical microscopy (OM) and X-ray diffraction (XRD) were also
used. It is concluded that irrespective of the protocol followed for preparing
the mixtures, mutual plasticization occurred in most cases (i.e., mixing of
domains of the two species) and not molecular mixing.
PMID- 27505025
TI - Topical anticholinergic drugs in the treatment of multiple hidrocystomas: a cross
over, randomized, double-blind, placebo-controlled study.
PMID- 27505026
TI - Multiparametric evaluation of low grade gliomas at follow-up: comparison between
diffusion and perfusion MR with (18)F-FDOPA PET.
AB - OBJECTIVE: To compare MRI using perfusion and diffusion techniques with 6-[(18)F]
fluoro-L-3,4-dihydroxyphenylalanine ((18)F-FDOPA) positron emission tomography
(PET) in the follow-up of low-grade gliomas (LGGs) and to identify the best
imaging parameter to differentiate patients with different prognosis. METHODS:
Between 2010 and 2015, 12 patients with a pathology-proven diagnosis of LGG and
MR (with perfusion and diffusion sequences) and a PET study during their follow
up were retrospectively included in our study. Cerebral blood volume (CBV) and
apparent diffusion coefficient (ADC) maps on MR studies and PET images were
evaluated using a region of interest-based method. All patients were categorized
as stable or as having progressive disease at 1-year follow-up. Statistical
analysis was performed using Pearson's correlation test and multivariate analysis
of variance (p < 0.05). RESULTS: No significant correlations were found between
PET parameters [maximum tumour-to-controlateral normal brain ratio (T/Nmax) and
tumour-to-striatum ratio] and ADC or relative CBV values measured in both PET
hotspot regions and areas of maximum signal alterations. T/Nmax demonstrated a
good sensitivity (83%) and specificity (100%) for differentiating two subgroups
of patients with different outcomes at 1-year-follow-up (p < 0.05). CONCLUSION:
Perfusion and diffusion MR images provide different information compared with
(18)F-FDOPA PET in LGGs during follow-up and therefore, they should be considered
as complementary tools in the evaluation of these tumours. (18)F-FDOPA PET showed
a significant prognostic role in the follow-up of LGGs and appeared to be a
better tool than MR advanced techniques for outcome prediction. These results
need to be confirmed with longitudinal studies on a larger population. ADVANCES
IN KNOWLEDGE: This is the first study that compared (18)F-FDOPA PET with
perfusion and diffusion MR in LGGs during follow-up. These preliminary results
highlight the importance of a multimodality approach in this field and evidence a
potential role for (18)F-FDOPA PET to predict patients at risk for tumour
progression.
PMID- 27505027
TI - Short and Long Term Behavioral and Pathological Changes in a Novel Rodent Model
of Repetitive Mild Traumatic Brain Injury.
AB - A history of concussion, particularly repeated injury, has been linked to an
increased risk for the development of neurodegenerative diseases, particularly
chronic traumatic encephalopathy (CTE). CTE is characterized by abnormal
accumulation of hyperphosphorylated tau and deficits in learning and memory. As
yet the mechanisms associated with the development of CTE are unknown.
Accordingly, the aim of the current study was to develop and characterize a novel
model of repetitive mTBI that accurately reproduces the key short and long-term
functional and histopathological features seen clinically. Forty male Sprague
Dawley rats were randomly assigned to receive 0, 1 or 3x mTBI spaced five days
apart using a modified version of the Marmarou impact-acceleration diffuse-TBI
model to deliver 110G of linear force. Functional outcomes were assessed six and
twelve weeks post-injury, with histopathology assessed twenty-four hours and
twelve weeks post-injury. Repetitive mTBI resulted in mild spatial and
recognition memory deficits as reflected by increased escape latency on the
Barnes maze and decreased time spent in the novel arm of the Y maze. There was a
trend towards increased anxiety-like behavior, with decreased time spent in the
inner portion of the open field. At 24 hours and 12 weeks post injury, repetitive
mTBI animals showed increased tau phosphorylation and microglial activation
within the cortex. Increases in APP immunoreactivity were observed in repetitive
mTBI animals at 12 weeks indicating long-term changes in axonal integrity. This
novel model of repetitive mTBI with its persistent cognitive deficits,
neuroinflammation, axonal injury and tau hyperphosphorylation, thus represents a
clinically relevant experimental approach to further explore the underlying
pathogenesis of CTE.
PMID- 27505028
TI - Pathophysiology of the Desmo-Adhesome.
AB - Advances in our understanding of desmosomal diseases have provided a clear
demonstration of the key role played by desmosomes in tissue and organ
physiology, highlighting the importance of their dynamic and finely regulated
structure. In this context, non-desmosomal regulatory molecules have acquired
increasing relevance in the study of this organelle resulting in extending the
desmosomal interactome, named the "desmo-adhesome." Spatiotemporal changes in the
expression and regulation of the desmo-adhesome underlie a number of genetic,
infectious, autoimmune, and malignant conditions. The aim of the present article
was to examine the structural and functional relationship of the desmosome, by
providing a comprehensive, yet focused overview of the constituents targeted in
human disease. The inclusion of the novel regulatory network in the desmo
adhesome pathophysiology opens new avenues to a deeper understanding of
desmosomal diseases, potentially unveiling pathogenic mechanisms waiting to be
explored. J. Cell. Physiol. 232: 496-505, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27505029
TI - Effects of Exposure to the Sound from Seismic Airguns on Pallid Sturgeon and
Paddlefish.
AB - This study examined the effects of exposure to a single acoustic pulse from a
seismic airgun array on caged endangered pallid sturgeon (Scaphirhynchus albus)
and on paddlefish (Polyodon spathula) in Lake Sakakawea (North Dakota, USA). The
experiment was designed to detect the onset of physiological responses including
minor to mortal injuries. Experimental fish were held in cages as close as 1 to 3
m from the guns where peak negative sound pressure levels (Peak- SPL) reached 231
dB re 1 MUPa (205 dB re 1 MUPa2.s sound exposure level [SEL]). Additional cages
were placed at greater distances in an attempt to develop a dose-response
relationship. Treatment and control fish were then monitored for seven days,
euthanized, and necropsied to determine injuries. Necropsy results indicated that
the probability of delayed mortality associated with pulse pressure following the
seven day monitoring period was the same for exposed and control fish of both
species. Exposure to a single pulse from a small air gun array (10,160 cm3) was
not lethal for pallid sturgeon and paddlefish. However, the risks from exposure
to multiple sounds and to sound exposure levels that exceed those reported here
remain to be examined.
PMID- 27505030
TI - Letter: The Impact of Guidelines on Clinical Practice: Survey of the Use of
Methylprednisolone for Acute Spinal Cord Injury.
PMID- 27505031
TI - Solution- and Solid-Phase Macrocyclization of Peptides by the Ugi-Smiles
Multicomponent Reaction: Synthesis of N-Aryl-Bridged Cyclic Lipopeptides.
AB - A new multicomponent methodology for the solution- and solid-phase
macrocyclization of peptides is described. The approach comprises the utilization
of the Ugi-Smiles reaction for the cyclization of 3-nitrotyrosine-containing
peptides either by the N-terminus or the lysine side-chain amino groups. Both the
on-resin and solution cyclizations took place with good to excellent efficiency
in the presence of an aldehyde and a lipidic isocyanide, while the use of
paraformaldehyde required an aminocatalysis-mediated imine formation prior to the
on-resin Ugi-Smiles ring closure. The introduction of a turn motif in the peptide
sequence facilitated the cyclization step, shortened the reaction time, and
delivered crude products with >90% purity. This powerful method provided a
variety of structurally novel N-aryl-bridged cyclic lipopeptides occurring as
single atropisomers.
PMID- 27505033
TI - Heterogeneity of osteoclast activity and bone turnover in different skeletal
sites.
AB - OBJECTIVE: To compare osteoclasts and bone turnover in the cranial and
appendicular skeletons of mice and determine whether estrogen depletion has an
impact on these differences. DESIGN: In vitro osteoclastogenesis (OCG) was
performed on osteoclasts precursors derived from calvarial, mandibular and
femoral bone marrow. In vitro, mature osteoclasts were stained with TRAP in
plastic petri dishes and with DAPI and Phalloidin on glass coverslips to identify
mature osteoclasts and compare osteoclast surface area and nuclei number in the
different bone sites, respectively. Quantification of osteoclast resorption pit
(Rpit) volume and surface area from different bone sites was achieved using
dentin slices stained with Picrosirius red and confocal microscopy. In vivo TRAP,
static and dynamic histomorphometric analyses were performed on 5-month-old mouse
calvarial, long bone and mandibular trabecular bone to compare bone resorption
and formation rates, respectively. Mice were ovariectomized (OVX) at 5 months of
age and sacrificed at 6 months of age to establish an osteoporosis model for
differences in osteoclasts activity and to monitor the changes in bone turnover
rates in the three bone sites upon estrogen depletion. RESULT: s Phalloidin
stained calvarial osteoclasts were larger compared to long bone and mandibular
osteoclasts. Rpits from osteoclasts derived from mandibular bone were smaller and
had lower volume values compared to long bone and calvarial bone Rpits. In vivo
analysis showed significant increases in bone formation rates in calvarial
trabecular bone compared to long bone and mandibular trabecular bone. Turnover
was enhanced upon estrogen depletion in calvarial trabecular bone. Resorption was
increased without a corresponding increase in bone formation in the trabecular
metaphysis of long bone. Mandibular trabecular bones do not appear to be affected
by OVX. CONCLUSION: The cranial and appendicular skeletons differ from one
another in that osteoclasts from calvarial bone have the highest resorptive
capacity which is coupled to bone formation both pre and post-OVX. Mandibular
bones show the lowest turnover rates and are not affected by OVX.
PMID- 27505032
TI - Chaperonin-Based Biolayer Interferometry To Assess the Kinetic Stability of
Metastable, Aggregation-Prone Proteins.
AB - Stabilizing the folded state of metastable and/or aggregation-prone proteins
through exogenous ligand binding is an appealing strategy for decreasing disease
pathologies caused by protein folding defects or deleterious kinetic transitions.
Current methods of examining binding of a ligand to these marginally stable
native states are limited because protein aggregation typically interferes with
analysis. Here, we describe a rapid method for assessing the kinetic stability of
folded proteins and monitoring the effects of ligand stabilization for both
intrinsically stable proteins (monomers, oligomers, and multidomain proteins) and
metastable proteins (e.g., low Tm) that uses a new GroEL chaperonin-based
biolayer interferometry (BLI) denaturant pulse platform. A kinetically controlled
denaturation isotherm is generated by exposing a target protein, immobilized on a
BLI biosensor, to increasing denaturant concentrations (urea or GuHCl) in a
pulsatile manner to induce partial or complete unfolding of the attached protein
population. Following the rapid removal of the denaturant, the extent of
hydrophobic unfolded/partially folded species that remains is detected by an
increased level of GroEL binding. Because this kinetic denaturant pulse is brief,
the amplitude of binding of GroEL to the immobilized protein depends on the
duration of the exposure to the denaturant, the concentration of the denaturant,
wash times, and the underlying protein unfolding-refolding kinetics; fixing all
other parameters and plotting the GroEL binding amplitude versus denaturant pulse
concentration result in a kinetically controlled denaturation isotherm. When
folding osmolytes or stabilizing ligands are added to the immobilized target
proteins before and during the denaturant pulse, the diminished population of
unfolded/partially folded protein manifests as a decreased level of GroEL binding
and/or a marked shift in these kinetically controlled denaturation profiles to
higher denaturant concentrations. This particular platform approach can be used
to identify small molecules and/or solution conditions that can stabilize or
destabilize thermally stable proteins, multidomain proteins, oligomeric proteins,
and, most importantly, aggregation-prone metastable proteins.
PMID- 27505034
TI - The downregulation of ANGPTL4 inhibits the migration and proliferation of tongue
squamous cell carcinoma.
AB - OBJECTIVE: Tongue squamous cell carcinoma (TSCC) is the most common malignant
cancer in the oral cavity, with a high rate of metastasis to the neck lymphoid
node. Angiopoietin-like protein 4 (ANGPTL4) and microvessel density (MVD) may be
novel indicators for tumor metastasis. The aim of the present study was to
investigate the expression and function of ANGPTL4 in TSCC and the relationship
between ANGPTL4 and MVD. METHODS: The expression levels of ANGPTL4 and MVD (CD34)
were analyzed in 65 TSCC specimens and the adjacent non-cancerous tissues using
immunohistochemistry (IHC). siRNA was delivered into TSCCA cells to downregulate
ANGPTL4 expression. Subsequently, validation with real-time RT-PCR and western
blot analyses was performed to analyze ANGPTL4 expression levels. In addition, a
proliferation assay, migration and invasion assays were carried out. RESULTS:
ANGPTL4 expression was associated with tumor stage, lymph node metastasis and MVD
expression. Cox regression analysis showed that high levels of ANGPTL4 expression
were closely associated with poor survival time. In vitro analyses using qRT-PCR
and western blot confirmed that ANGPTL4 was successfully inhibited in TSCCA
cells. Suppressing ANGPTL4 resulted in the inhibition of cell proliferation and
migration, but neither invasion nor cisplatin resistance was significantly
affected. CONCLUSION: High expression levels of ANGPTL4 are associated with the T
stage, lymphatic metastasis, angiogenesis and poor overall survival in TSCC
patients. The downregulation of ANGPTL4 inhibits the migration and proliferation
of cells in TSCC. Taken together, ANGPTL4 may serve as a novel biomarker and
therapeutic target for TSCC.
PMID- 27505035
TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin Mediated Cleft palate by Mouse Embryonic
Palate Mesenchymal Cells.
AB - OBJECTIVE: To evaluate the effects of mouse embryonic palatal mesenchymal (MEPM)
cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced. STUDY DESIGN: An
experimental study at Xinxiang Medical University. METHODS: Primary MEPM cells
were derived from palatal tissue on 30 pregnant C57BL/6 female mice (embryonic
day13, GD13). The MEPM cells were placed in a humidified incubator at 37 degrees
C with 5% CO2 atmosphere with media replaced every other day. The third passage
cells were seeded, and one part of cells were treated with 10nM TCDD (TCDD
group). And others were treated with DMSO (<=0.05%, as control group). After 72h,
MTT assay was analysed cell viability. Scratch wound-healing was analysed cell
motility. Flow cytometry was analysed cell apoptosis and cycle. Western blot was
analysed the expression of cyclinE, CDK2, P16 and P21. RESULTS: TCDD inhibited
the growth and migration of MEPM cells, while increased cell apoptosis. TCDD
exposure inhibited the progression of cells from G1 to S phase and tended to
reduce the number of cells entering the G2/M phase. TCDD inhibited expression of
cyclinE and CDK2 at the protein level, instead increased the expression of P16
and p21 proteins. CONCLUSIONS: TCDD might induce cleft palate by altering MEPM
cells.
PMID- 27505036
TI - Race does not predict the development of metastases in men with nonmetastatic
castration-resistant prostate cancer.
AB - BACKGROUND: Although race is associated with prostate cancer progression in early
stage disease, once men have advanced disease, it is unclear whether race
continues to predict a poor outcome. The authors hypothesized that, in an equal
access setting among patients with castration-resistant prostate cancer (CRPC)
and no known metastases (M0/Mx), black men would receive imaging tests at similar
rates as nonblack men (ie, there would be an equal opportunity to detect
metastases) but would have a higher risk of metastatic disease. METHODS: In
total, 837 men who were diagnosed with M0/Mx CRPC during 2000 through 2014 from 5
Veterans Affairs hospitals in the SEARCH (Shared Equal Access Regional Cancer
Hospital) database were analyzed. Data on all imaging tests after CRPC diagnosis
were collected, including date, type, and outcome. Multivariable Cox models were
used to test associations between race and the time to first metastasis, first
bone metastasis, first bone scan, second bone scan among men who had a negative
first bone scan, and overall survival. RESULTS: Black men (n = 306) were equally
as likely as nonblack men (n = 531) to receive a first and second bone scan after
a diagnosis of CRPC. There were no significant differences in the risk of
developing any metastases, bone metastases, time to bone scans, or overall
survival between black men and nonblack men (all P > .2). CONCLUSIONS: The lack
of racial differences in the development of metastases and scanning practices
observed in this study suggests that, once men have a diagnosis of M0/Mx CRPC,
race may not be a prognostic factor. Efforts to understand prostate cancer racial
disparities may derive greater benefit by focusing on the risk of developing
prostate cancer and on the outcomes of men who have early stage disease. Cancer
2016;122:3848-3855. (c) 2016 American Cancer Society.
PMID- 27505037
TI - Real Time Monitoring of Containerless Microreactions in Acoustically Levitated
Droplets via Ambient Ionization Mass Spectrometry.
AB - Direct in-droplet (in stillo) microreaction monitoring using acoustically
levitated micro droplets has been achieved by combining acoustic (ultrasonic)
levitation for the first time with real time ambient tandem mass spectrometry
(MS/MS). The acoustic levitation and inherent mixing of microliter volumes of
reactants (3 MUL droplets), yielding total reaction volumes of 6 MUL, supported
monitoring the acid-catalyzed degradation reaction of erythromycin A. This
reaction was chosen to demonstrate the proof-of-principle of directly monitoring
in stillo microreactions via hyphenated acoustic levitation and ambient
ionization mass spectrometry. The microreactions took place completely in stillo
over 30, 60, and 120 s within the containerless stable central pressure node of
an acoustic levitator, thus readily promoting reaction miniaturization. For the
evaluation of the miniaturized in stillo reactions, the degradation reactions
were also carried out in vials (in vitro) with a total reaction volume of 400
MUL. The reacted in vitro mixtures (6 MUL total) were similarly introduced into
the acoustic levitator prior to ambient ionization MS/MS analysis. The in stillo
miniaturized reactions provided immediate real-time snap-shots of the degradation
process for more accurate reaction monitoring and used a fraction of the
reactants, while the larger scale in vitro reactions only yielded general
reaction information.
PMID- 27505038
TI - BAIT DEVELOPMENT FOR ORAL DELIVERY OF PHARMACEUTICALS TO RACCOONS (PROCYON LOTOR)
AND STRIPED SKUNKS (MEPHITIS MEPHITIS).
AB - Oral vaccination is one tool used to control wildlife diseases. A challenge to
oral vaccination is identifying baits specific to target species. The US has been
conducting oral vaccination against rabies since the 1990s. Improvements in bait
development will hasten disease elimination. In Colorado, we examined a novel
bait for oral vaccination and offered two different flavors, sweet and fish, to
captive raccoons ( Procyon lotor ) and striped skunks ( Mephitis mephitis ) to
assess consumption and flavor preference and observed bait removal by target and
nontarget species in the field. During captive trials, raccoons and skunks
consumed 98% and 87% of offered baits, respectively. Baits contained a sachet to
simulate a vaccine package. Raccoons and skunks consumed 98% and 94% of the
sachets, respectively. All unconsumed sachets were punctured, suggesting that
animals had oral exposure to the contents. Raccoons preferred fish-flavored bait,
but skunks did not have a preference. In the field, raccoons consumed the most
baits, followed by fox squirrels ( Sciurus niger ). Other rabies host species
(striped skunks, red foxes [ Vulpes vulpes ], coyotes [ Canis latrans ]) had very
low visitation and were never observed consuming baits. High consumption rates by
raccoons and skunks in captivity and observance of raccoons consuming baits in
the field suggest that these baits may be useful for oral delivery of
pharmaceuticals. Further field research is warranted to determine how to best
optimize bait delivery.
PMID- 27505039
TI - FORCED MOLT IN FOUR JUVENILE YELLOW-EYED PENGUINS (MEGADYPTES ANTIPODES).
AB - Penguins are dependent on waterproof plumage for survival. The molt in sub
Antarctic penguin species is a seasonal and catastrophic process during which the
animals go through periods of fasting and high levels of stress. Their entire
plumage is usually replaced in 3 wk. Attempts at consistent hormonal induction of
molt in penguins have been unsuccessful. Four Yellow-eyed Penguins ( Megadyptes
antipodes ) were referred for treatment at Wildbase, Massey University,
Palmerston North, New Zealand, in late April 2014, following loss of
waterproofing, feather breakage, increased body weight, pododermatitis, and
damage to caudal feathers from hock sitting. Feather plucking of damaged areas to
stimulate feather regrowth was attempted with poor results. Waiting 10-12 mo for
a natural molt was not tenable. Catastrophic molt was induced by treatment with
10 g/kg of fresh beef thyroid gland orally once a day. The molt was complete in
18-26 d during which the animals regained full plumage and waterproofing after
feather regrowth. The forced molt feathers had abnormal pigmentation but were of
sufficient quality to allow release of the birds back to the wild.
PMID- 27505040
TI - Dermatophilus congolensis Infection in Platypus ( Ornithorhynchus anatinus ),
Tasmania, Australia, 2015.
AB - We report disease due to Dermatophilus congolensis infection in three of 13 (23%)
platypuses ( Ornithorhynchus anatinus ) from a catchment in Tasmania, Australia.
This pathogen has not previously been reported in platypuses. Two of the three
infected platypuses had extensive scab formations, but no substantial hair loss
was apparent.
PMID- 27505041
TI - Formation of Ultrathin Liesegang Patterns.
AB - For many years, it has been believed that self-organized periodic ring structures
known by the name of Liesegang patterns (LPs) are formed only in quite thick
media, typically thicker than at least several micrometers. Actually growing LPs
in ultrathin films is extremely difficult because of the drying of film and
susceptibility to rapid capillary wetting. The present work reports how we obtain
successful LPs in ultrathin films of 65 nm thick. The key parameters are
temperature control and the introduction of equilibrium water vapor in the sample
environment. Atomic force microscope images clearly showed that the LPs are
composed of 300-600 nm laterally coagulated particles. We have also evaluated the
densities and thicknesses of the ultrathin films by X-ray reflectivity. During
the present research, new patterns, which are different from ordinary LPs, have
been discovered for the first time in the outermost part of the whole pattern.
Studying LPs in ultrathin films may help to forge a better understanding of the
mechanism underlying the intriguing phenomenon. Because of nanoscale scale
thicknesses, self-organized periodic structures including so-called LPs will open
up new opportunities in nanotechnologies.
PMID- 27505042
TI - Oxazolinyl derivatives of [17(20)E]-21-norpregnene differing in the structure of
A and B rings. Facile synthesis and inhibition of CYP17A1 catalytic activity.
AB - Five 4,5-dihydro-1,3-oxazole derivatives of [17(20)E]-21-norpregnene, comprising
3beta-hydroxy-5-ene (1), 3,6-dioxo-4-ene (2), 3-oxo-4-ene (3), 3alpha,5alpha
cyclo-6-oxo (4), 3beta-hydroxy-6-oxo (5) fragments were synthesized. Synthesis
was conducted with improved procedure, based on reaction of suitably protected
[17(20)E]-pregnen-21-oic acids with ethanolamine in presence of triphenyl
phosphine, carbon tetrachloride, and triethyl amine. Potency of the compounds 1-5
to inhibit 17alpha-hydroxylase/17,20-lyase (CYP17A1) activity was studied by
highly sensitive electrochemical method, using the enzyme immobilization
technique. Compounds 1 and 3 were found to be potent CYP17A1 inhibitors,
compounds 2 and 5 were not active, compound 4 strongly and irreversibly
suppressed the enzyme activity. Molecular docking of compounds 1-5 in the active
site of CYP17A1 showed that positions of all compounds in the enzyme active site
were similar.
PMID- 27505043
TI - Selective Cooperation in Early Childhood - How to Choose Models and Partners.
AB - Cooperation is essential for human society, and children engage in cooperation
from early on. It is unclear, however, how children select their partners for
cooperation. We know that children choose selectively whom to learn from (e.g.
preferring reliable over unreliable models) on a rational basis. The present
study investigated whether children (and adults) also choose their cooperative
partners selectively and what model characteristics they regard as important for
cooperative partners and for informants about novel words. Three- and four-year
old children (N = 64) and adults (N = 14) saw contrasting pairs of models
differing either in physical strength or in accuracy (in labeling known objects).
Participants then performed different tasks (cooperative problem solving and word
learning) requiring the choice of a partner or informant. Both children and
adults chose their cooperative partners selectively. Moreover they showed the
same pattern of selective model choice, regarding a wide range of model
characteristics as important for cooperation (preferring both the strong and the
accurate model for a strength-requiring cooperation tasks), but only prior
knowledge as important for word learning (preferring the knowledgeable but not
the strong model for word learning tasks). Young children's selective model
choice thus reveals an early rational competence: They infer characteristics from
past behavior and flexibly consider what characteristics are relevant for certain
tasks.
PMID- 27505045
TI - Comparison of the Results of Early Flap Coverage with Late Flap Coverage in High
Voltage Electrical Injury.
AB - Patients with high-voltage electrical injuries had very high rates of infection,
morbidity, and limb amputation. The results of early and late flap coverage in
these patients were prospectively compared. The patients were divided into two
groups, early flap group (<=3 weeks) and late flap group (>3 weeks), according to
the length of time from injury to wound coverage with flap. Age, sex, demographic
data, time taken for flap coverage, time taken for pedicle division, time taken
to discharge, wound infection, range of motion in joints, amputation, mortality,
and outcome were gathered in a special questionnaire. This study included 55
patients, 31 within the early flap group and 24 within the late flap group. Of
the 55 patients, 94.6% were male; mean (SD) of age was 29.04 (10.11) and of TBSA
was 13.8 (10.07). Length of stay was significantly longer in the late flap group.
The rates of infection and amputation were lower in the early flap group. There
was no correlation between the type and the number of flaps and amputations.
Early flap repair reduces the length of stay by 56%, rate of amputation by 54%,
and also 86.1% in the rate of infection in the burn site.
PMID- 27505044
TI - OxaD: A Versatile Indolic Nitrone Synthase from the Marine-Derived Fungus
Penicillium oxalicum F30.
AB - Indole alkaloids are a diverse class of natural products known for their wide
range of biological activities and complex chemical structures. Rarely observed
in this class are indolic nitrones, such as avrainvillamide and waikialoid, which
possess potent bioactivities. Herein the oxa gene cluster from the marine-derived
fungus Penicillium oxalicum F30 is described along with the characterization of
OxaD, a flavin-dependent oxidase that generates roquefortine L, a nitrone-bearing
intermediate in the biosynthesis of oxaline. Nitrone functionality in
roquefortine L was confirmed by spectroscopic methods and 1,3-dipolar
cycloaddition with methyl acrylate. OxaD is a versatile biocatalyst that converts
an array of semisynthetic roquefortine C derivatives bearing indoline systems to
their respective nitrones. This work describes the first implementation of a
nitrone synthase as a biocatalyst and establishes a novel platform for late-stage
diversification of a range of complex natural products.
PMID- 27505046
TI - Profile of Patients Without Burn Scar Contracture Development.
AB - Burn scar contractures (BSCs) are a frequently recognized problem for survivors
of burn injury. In the burn literature, many reports focus on the frequency and
factors associated with the BSC development. To the contrary, few burn
rehabilitation publications report on patients who are able to successfully avoid
developing BSC. From a prospective, multicenter study, data were extracted and
reviewed on a group of 56 adult burn survivors who were discharged from their
acute hospitalization without any measured BSCs. Forty-three variables with a
recognized or presumed association with the development of BSCs were analyzed and
are reported. Highlighted features of the noncontracted group included being an
adult male with an educated background and few associated physical, medical, or
social problems. The group had relatively small burn sizes that nonetheless
required hospitalization. Despite the overall TBSA, the majority of the burn
areas required skin grafting, although this area also represented a small area.
The patient group had a longer than expected hospital stay. Rehabilitation was
provided to patients on 80% of their hospital days. In addition, patients
received sufficient rehabilitation treatment based on the number of cutaneous
functional units involved in the burn injury. Patients were judged to have a high
pain tolerance and compliant with rehabilitation. The results of this study
document the clinical circumstances that patients with burn injury can be
discharged from their acute hospitalization with the development of BSC. This
study challenges the rehabilitation personnel to expand the upper limit of burn
severity that can result in similar positive outcomes.
PMID- 27505047
TI - MicroRNA-148b Acts as a Tumor Suppressor in Cervical Cancer by Inducing G1/S
Phase Cell Cycle Arrest and Apoptosis in a Caspase-3-Dependent Manner.
AB - BACKGROUND The purpose of our study was to investigate the role of microRNA (miR)
148b in cervical cancer. MATERIAL AND METHODS The expression of miR-148b was
determined in HPV-16-immortalized cervical epithelial cell line CRL-2614 cells
and in cervical cancer cell line HeLa cells. The miR-148b mimics or scrambled RNA
were then transfected into Hela cells. Forty-eight hours after transfection, the
mRNA expression of miR-148b and DNA methyltransferase 1 (DNMT1) were confirmed.
Cell proliferation ability (cell viability and colony formation ability),
invasion ability, and apoptosis were assessed after transfection with miR-148b
mimics or scrambled RNA, as well as the protein expression of cyclin D1 and
caspase-3. RESULTS The expression of miR-148b was significantly downregulated in
HeLa cells compared with CRL2614 cells (P<0.05), but was statistically
upregulated by transfection with miR-148b mimics compared with the cells
transfected with scrambled RNA (P<0.05). Also, we found that the expression of
DNMT1 was significantly decreased by transfection with miR-148b mimics (P<0.05).
Additionally, miR-148b mimics significantly decreased the cell proliferation
ability and invasion ability, and statistically induced apoptosis. Furthermore,
the expression of cyclin D1 protein was significantly decreased and the
expression of caspase-3 protein was significantly increased by miR-148b mimics
compared with that in the cells transfected with scrambled RNA (P<0.05).
CONCLUSIONS Our results suggest that overexpression of miR-148b protects against
cervical cancer by inducing G1/S-phase cell cycle arrest and apoptosis through
caspase-3-dependent manner, and overexpression of miR-148b might develop a
therapeutic intervention for cervical cancer.
PMID- 27505048
TI - Almost human: Anthropomorphism increases trust resilience in cognitive agents.
AB - We interact daily with computers that appear and behave like humans. Some
researchers propose that people apply the same social norms to computers as they
do to humans, suggesting that social psychological knowledge can be applied to
our interactions with computers. In contrast, theories of human-automation
interaction postulate that humans respond to machines in unique and specific
ways. We believe that anthropomorphism-the degree to which an agent exhibits
human characteristics-is the critical variable that may resolve this apparent
contradiction across the formation, violation, and repair stages of trust. Three
experiments were designed to examine these opposing viewpoints by varying the
appearance and behavior of automated agents. Participants received advice that
deteriorated gradually in reliability from a computer, avatar, or human agent.
Our results showed (a) that anthropomorphic agents were associated with greater
trust resilience, a higher resistance to breakdowns in trust; (b) that these
effects were magnified by greater uncertainty; and c) that incorporating human
like trust repair behavior largely erased differences between the agents.
Automation anthropomorphism is therefore a critical variable that should be
carefully incorporated into any general theory of human-agent trust as well as
novel automation design.
PMID- 27505049
TI - Effects of cues in a binary categorization task on dual-task performance, mental
workload, and effort.
AB - Binary cues help operators perform binary categorization tasks, such as
monitoring for system failures. They may also allow them to attend to other tasks
they concurrently perform. If the time saved by using cues is allocated to other
concurrent tasks, users' overall effort may remain unchanged. In 2 experiments,
participants performed a simulated quality control task, together with a tracking
task. In half the experimental blocks cues were available, and participants could
use them in their decisions about the quality of products (intact or faulty). In
Experiment 1, the difficulty of tracking was constant, while in Experiment 2,
tracking difficulty differed in the 2 halves of the experiment. In both
experiments, participants reported on the NASA Task Load Index that cues improved
their performance and reduced their frustration. Consequently, their overall
score on mental workload (MWL) was lower with cues. They also reported, however,
that cues did not reduce their effort. We conclude that cues and other forms of
automation may support task performance and reduce overall MWL, but this will not
necessarily mean that users will work less hard. Thus, effort and overall MWL
should be evaluated separately, if one wants to obtain a full picture of the
effects of automation. (PsycINFO Database Record
PMID- 27505050
TI - Increased prevalence of human herpesvirus type 8 (HHV-8) genome among blood
donors from North-Western Argentina.
AB - The prevalence of HHV-8 infection varies widely in South American populations,
displaying geographical variations in its distribution. The heterogeneous genetic
contributions provided by the transatlantic parental populations that modified
the Native American genomes may explain this epidemiological observation. Aiming
to determine the prevalence of HHV-8 genome among healthy South American blood
donors and its potential association with genetic ancestry, 772 individuals were
screened by a highly sensitive PCR protocol and ancestry was assessed in 414
samples. HHV-8 DNA was significantly more prevalent among North-western
Argentines than among those from the metropolitan region (P = 0.001) and
Bolivians (P = 0.0008), but no differences were found when compared with
Peruvians and Paraguayans. Although significant differences were observed in the
ancestry components of the studied populations, no association was found in the
genetic admixture between HHV-8 [+] and HHV-8 [-] samples from the same place.
These results support the hypothesis of the existence of geographical factors
related to HHV-8 prevalence which could be explained by the presence of specific
risk factors, cultural characteristics or behaviors, probably related to
contaminated saliva and/or sexual transmission. The presence of HHV-8 in South
American blood units available for transfusion and an increased risk of infection
in some provinces of North-western Argentina represent a hazard for
immunosuppressed recipients. J. Med. Virol. 89:518-527, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27505052
TI - Reflectometry-Ellipsometry Reveals Thickness, Growth Rate, and Phase Composition
in Oxidation of Copper.
AB - The oxidation of copper is a complicated process. Copper oxide develops two
stable phases at room temperature and standard pressure (RTSP): cuprous oxide
(Cu2O) and cupric oxide (CuO). Both phases have different optical and electrical
characteristics that make them interesting for applications such as solar cells
or resistive switching devices. For a given application, it is necessary to
selectively control oxide thickness and cupric/cuprous oxide phase volume
fraction. The thickness and composition of a copper oxide film growing on the
surface of copper widely depend on the characteristics of as-deposited copper. In
this Research Article, two samples, copper films prepared by two different
deposition techniques, electron-beam evaporation and sputtering, were studied. As
the core part of the study, the formation of the oxidized copper was analyzed
routinely over a period of 253 days using spectroscopic polarized reflectometry
spectroscopic ellipsometry (RE). An effective medium approximation (EMA) model
was used to fit the RE data. The RE measurements were complemented and validated
by using X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM)
and X-ray diffraction (XRD). Our results show that the two samples oxidized under
identical laboratory ambient conditions (RTSP, 87% average relative humidity)
developed unique oxide films following an inverse-logarithmic growth rate with
thickness and composition different from each other over time. Discussion is
focused on the ability of RE to simultaneously extract thickness (i.e., growth
rate) and composition of copper oxide films and on plausible physical mechanisms
responsible for unique oxidation habits observed in the two copper samples. It
appears that extended surface characteristics (i.e., surface roughness and grain
boundaries) and preferential crystalline orientation of as-deposited
polycrystalline copper films control the growth kinetics of the copper oxide
film. Analysis based on a noncontact and nondestructive measurement, such as RE,
to extract key material parameters is beneficial for conveniently understanding
the oxidation process that would ultimately enable copper oxide-based devices at
manufacturing scales.
PMID- 27505051
TI - Core Outcomes for Colorectal Cancer Surgery: A Consensus Study.
AB - BACKGROUND: Colorectal cancer (CRC) is a major cause of worldwide morbidity and
mortality. Surgical treatment is common, and there is a great need to improve the
delivery of such care. The gold standard for evaluating surgery is within well
designed randomized controlled trials (RCTs); however, the impact of RCTs is
diminished by a lack of coordinated outcome measurement and reporting. A solution
to these issues is to develop an agreed standard "core" set of outcomes to be
measured in all trials to facilitate cross-study comparisons, meta-analysis, and
minimize outcome reporting bias. This study defines a core outcome set for CRC
surgery. METHODS AND FINDINGS: The scope of this COS includes clinical
effectiveness trials of surgical interventions for colorectal cancer. Excluded
were nonsurgical oncological interventions. Potential outcomes of importance to
patients and professionals were identified through systematic literature reviews
and patient interviews. All outcomes were transcribed verbatim and categorized
into domains by two independent researchers. This informed a questionnaire survey
that asked stakeholders (patients and professionals) from United Kingdom CRC
centers to rate the importance of each domain. Respondents were resurveyed
following group feedback (Delphi methods). Outcomes rated as less important were
discarded after each survey round according to predefined criteria, and remaining
outcomes were considered at three consensus meetings; two involving international
professionals and a separate one with patients. A modified nominal group
technique was used to gain the final consensus. Data sources identified 1,216
outcomes of CRC surgery that informed a 91 domain questionnaire. First round
questionnaires were returned from 63 out of 81 (78%) centers, including 90
professionals, and 97 out of 267 (35%) patients. Second round response rates were
high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome
domains being retained after the first and second surveys, respectively.
Consensus meetings generated agreement on a 12 domain COS. This constituted five
perioperative outcome domains (including anastomotic leak), four quality of life
outcome domains (including fecal urgency and incontinence), and three oncological
outcome domains (including long-term survival). CONCLUSION: This study used
robust consensus methodology to develop a core outcome set for use in colorectal
cancer surgical trials. It is now necessary to validate the use of this set in
research practice.
PMID- 27505053
TI - Behavioral interventions for improving contraceptive use among women living with
HIV.
AB - BACKGROUND: Contraception services can help meet the family planning goals of
women living with HIV as well as prevent mother-to-child transmission. Due to
antiretroviral therapy, survival has improved for people living with HIV, and
more HIV-positive women may desire to have a child or another child. Behavioral
interventions, involving counseling or education, can help women choose and use
an appropriate contraceptive method. OBJECTIVES: We systematically reviewed
studies of behavioral interventions for HIV-positive women intended to inform
contraceptive choice, encourage contraceptive use, or promote adherence to a
contraceptive regimen. SEARCH METHODS: Until 2 August 2016, we searched MEDLINE,
CENTRAL, Web of Science, POPLINE, ClinicalTrials.gov and ICTRP. For the initial
review, we examined reference lists and unpublished project reports, and we
contacted investigators in the field. SELECTION CRITERIA: Studies evaluated a
behavioral intervention for improving contraceptive use for family planning (FP).
The comparison could have been another behavioral intervention, usual care, or no
intervention. We also considered studies that compared HIV-positive versus HIV
negative women. We included non-randomized studies as well as randomized
controlled trials (RCTs).Primary outcomes were pregnancy and contraception use,
e.g. uptake of a new method or improved use or continuation of current method.
Secondary outcomes were knowledge of contraceptive effectiveness and attitude
about contraception or a specific contraceptive method. DATA COLLECTION AND
ANALYSIS: Two authors independently extracted the data. One entered the data into
RevMan and a second verified accuracy. We evaluated RCTs according to recommended
principles. For non-randomized studies, we examined the quality of evidence using
the Newcastle-Ottawa Quality Assessment Scale. Given the need to control for
confounding factors in non-randomized studies, we used adjusted estimates from
the models when available. Where we did not have adjusted analyses, we calculated
the odds ratio (OR) with 95% confidence interval (CI). Due to varied study
designs and interventions, we did not conduct meta-analysis. MAIN RESULTS: With
three new reports, 10 studies from seven African countries met our eligibility
criteria. Eight non-randomized studies included 8980 participants. Two cluster
RCTs had 7136 participants across 36 sites. Three studies compared a special FP
intervention versus usual care, three examined FP services integrated with HIV
services, and four compared outcomes for HIV-positive and HIV-negative women.In
four studies with high or moderate quality evidence, the special intervention was
associated with contraceptive use or pregnancy. A study from Nigeria compared
enhanced versus basic FP services. All sites had integrated FP and HIV services.
Women with enhanced services were more likely to use a modern contraceptive
method versus women with basic services (OR 2.48, 95% CI 1.31 to 4.72). A cluster
RCT conducted in Kenya compared integrated FP and HIV services versus standard
referral to a separate FP clinic. Women with integrated services were more likely
to use more effective contraception (adjusted OR 1.81, 95% CI 1.24 to 2.63).
Another cluster RCT compared an HIV prevention and FP intervention versus usual
care in Kenya, Namibia, and Tanzania. Women at the special intervention sites in
Tanzania were more likely to use highly effective contraception (adjusted OR
2.25, 95% CI 1.24 to 4.10). They were less likely to report unprotected sex (no
condom use) at last intercourse (adjusted OR 0.23, 95% CI 0.14 to 0.40). Across
the three countries, women at the special intervention sites were less likely to
report any unprotected sex in the past two weeks (adjusted OR 0.56, 95% CI 0.32
to 0.99). A study in Cote d'Ivoire integrated HIV and FP services. HIV-positive
women had a lower incidence of undesired pregnancy, but not overall pregnancy,
compared with HIV-negative women (1.07 versus 2.38; reported P = 0.023). AUTHORS'
CONCLUSIONS: The studies since 2009 focused on using modern or more effective
methods of contraception. In those later reports, training on FP methods and
counseling was more common, which may strengthen the intervention and improve the
ability to meet clients' needs. The quality of evidence was moderate from the
more recent studies and low for those from the 1990s.Comparative research
involving contraceptive counseling for HIV-positive women is limited. The FP
field needs better ways to help women choose an appropriate contraceptive and
continue using that method. Improved counseling methods are especially needed for
limited resource settings, such as clinics focusing on people living with HIV.
PMID- 27505054
TI - Two Simple and Efficient Algorithms to Compute the SP-Score Objective Function of
a Multiple Sequence Alignment.
AB - BACKGROUND: Multiple sequence alignment (MSA) is a crucial step in many molecular
analyses and many MSA tools have been developed. Most of them use a greedy
approach to construct a first alignment that is then refined by optimizing the
sum of pair score (SP-score). The SP-score estimation is thus a bottleneck for
most MSA tools since it is repeatedly required and is time consuming. RESULTS:
Given an alignment of n sequences and L sites, I introduce here optimized
solutions reaching O(nL) time complexity for affine gap cost, instead of O(n2L),
which are easy to implement.
PMID- 27505055
TI - To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in
Different Clinical Classifications of PCOS.
AB - AIMS: There are emerging data indicating an association between PCOS (polycystic
ovary syndrome) and metabolic derangements with potential impact on its clinical
presentation. This study aims to evaluate the pathophysiological processes beyond
PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their
possible interaction. Differences between the two established classifications of
the disease should be additionally evaluated. METHODS: A metabolic
characterization was performed in 53 untreated PCOS patients as well as 20
controls including an extended oral glucose tolerance test (OGTT, to assess
insulin sensitivity, secretion and beta-cell function) in addition to a detailed
examination of ectopic lipid content in muscle and liver by nuclear magnetic
resonance spectroscopy. RESULTS: Women with PCOS classified by the original NIH
1990 definition showed a more adverse metabolic risk profile compared to women
characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic
derangements were observed in both subgroups, including altered shapes of OGTT
curves, impaired insulin action and hyperinsulinemia due to increased secretion
and attenuated hepatic extraction. No differences were observed for ectopic
lipids between the groups. However, particularly hepatocellular lipid content was
significantly related to clinical parameters of PCOS like whole body insulin
sensitivity, dyslipidemia and free androgen index. CONCLUSIONS: Subtle
alterations in carbohydrate metabolism are present in both PCOS classifications,
but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS
and controls did not differ in ectopic lipids, however, liver fat was tightly
related to hyperandrogenism and an adverse metabolic risk profile.
PMID- 27505056
TI - Alternatively Activated Mononuclear Phagocytes from the Skin Site of Infection
and the Impact of IL-4Ralpha Signalling on CD4+T Cell Survival in Draining Lymph
Nodes after Repeated Exposure to Schistosoma mansoni Cercariae.
AB - In a murine model of repeated exposure of the skin to infective Schistosoma
mansoni cercariae, events leading to the priming of CD4 cells in the skin
draining lymph nodes were examined. The dermal exudate cell (DEC) population
recovered from repeatedly (4x) exposed skin contained an influx of mononuclear
phagocytes comprising three distinct populations according to their differential
expression of F4/80 and MHC-II. As determined by gene expression analysis, all
three DEC populations (F4/80-MHC-IIhigh, F4/80+MHC-IIhigh, F4/80+MHC-IIint)
exhibited major up-regulation of genes associated with alternative activation.
The gene encoding RELMalpha (hallmark of alternatively activated cells) was
highly up-regulated in all three DEC populations. However, in 4x infected mice
deficient in RELMalpha, there was no change in the extent of inflammation at the
skin infection site compared to 4x infected wild-type cohorts, nor was there a
difference in the abundance of different mononuclear phagocyte DEC populations.
The absence of RELMalpha resulted in greater numbers of CD4+ cells in the skin
draining lymph nodes (sdLN) of 4x infected mice, although they remained hypo
responsive. Using mice deficient for IL-4Ralpha, in which alternative activation
is compromised, we show that after repeated schistosome infection, levels of
regulatory IL-10 in the skin were reduced, accompanied by increased numbers of
MHC-IIhigh cells and CD4+ T cells in the skin. There were also increased numbers
of CD4+ T cells in the sdLN in the absence of IL-4Ralpha compared to cells from
singly infected mice. Although their ability to proliferate was still
compromised, increased cellularity of sdLN from 4x IL-4RalphaKO mice correlated
with reduced expression of Fas/FasL, resulting in decreased apoptosis and cell
death but increased numbers of viable CD4+ T cells. This study highlights a
mechanism through which IL-4Ralpha may regulate the immune system through the
induction of IL-10 and regulation of Fas/FasL mediated cell death.
PMID- 27505058
TI - Depression correlates with quality of life in people with epilepsy independent of
the measures used.
AB - PURPOSE: A number of studies have suggested that depressed mood is one of the
most important predictors of quality of life (QoL) in patients with epilepsy.
However, the QoL measure used in previous studies was limited to the Quality of
Life in Epilepsy (QOLIE) scales. It could be questioned whether correlation of
QOLIE with measures of depression is influenced by the properties of the
instruments used rather than being a valid effect. By using visual analogue
scales, the current study aimed to clarify whether depression and QoL are truly
correlated in patients with epilepsy. METHODS: Data from a sample of 261
outpatients with epilepsy attending the Epilepsy Clinics of the Atkinson Morley
Outpatient Department, St George's Hospital in London, were analyzed. Patients
were screened using the European Quality-of-Life scale (EQ-5D-3L) which includes
an overall visual analogue score (EQ-VAS), the Emotional Thermometer (ET7), the
Beck Depression inventory-II (BDI-II), the Hospital Anxiety and Depression scale
(HADS), and the Major Depression inventory (MDI). RESULTS: Depression was found
to significantly correlate with EQ-VAS score with r coefficient ranging from 0.42
to 0.51 and r(2) coefficients ranging between 0.18 and 0.26. In addition, we
identified patients who were depressed according to DSM-IV criteria (MD) and
those with atypical forms of depression (AD). The EQ-5D-3L scores in these
subjects compared with those without depression (ND) showed a different impact of
AD and MD on QoL. CONCLUSIONS: The relationship between depression and QoL in
people with epilepsy has been demonstrated to be a robust and valid effect, not a
result of potential bias of the specific measures used. However, the strength of
the association is influenced by the individual instrument. Atypical or
subsyndromic forms of depression are as relevant as DSM-based depression in terms
of impact on QoL.
PMID- 27505057
TI - An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon
Responses against Multiple Respiratory Pathogens.
AB - The healthy lung maintains a steady state of immune readiness to rapidly respond
to injury from invaders. Integrins are important for setting the parameters of
this resting state, particularly the epithelial-restricted alphaVbeta6 integrin,
which is upregulated during injury. Once expressed, alphaVbeta6 moderates acute
lung injury (ALI) through as yet undefined molecular mechanisms. We show that the
upregulation of beta6 during influenza infection is involved in disease
pathogenesis. beta6-deficient mice (beta6 KO) have increased survival during
influenza infection likely due to the limited viral spread into the alveolar
spaces leading to reduced ALI. Although the beta6 KO have morphologically normal
lungs, they harbor constitutively activated lung CD11b+ alveolar macrophages (AM)
and elevated type I IFN signaling activity, which we traced to the loss of beta6
activated transforming growth factor-beta (TGF-beta). Administration of exogenous
TGF-beta to beta6 KO mice leads to reduced numbers of CD11b+ AMs, decreased type
I IFN signaling activity and loss of the protective phenotype during influenza
infection. Protection extended to other respiratory pathogens such as Sendai
virus and bacterial pneumonia. Our studies demonstrate that the loss of one
epithelial protein, alphaVbeta6 integrin, can alter the lung microenvironment
during both homeostasis and respiratory infection leading to reduced lung injury
and improved survival.
PMID- 27505059
TI - Primary Hydromorphone-Related Intrathecal Catheter Tip Granulomas: Is There a
Role for Dose and Concentration?
AB - BACKGROUND: Intrathecal drug delivery therapy has been used effectively in
treating patients with intractable chronic pain. The development of an
intrathecal catheter tip granuloma (ICTG) related to delivery of intrathecal
opiates is a relatively infrequent, but potentially devastating complication.
While there are many morphine-related ICTG cases described, reports of
hydromorphone-related ICTG are limited. In addition, studies suggest a strong
correlation between the use of higher doses and concentrations of intrathecal
opiates and ICTG formation. OBJECTIVE: The objective of this study is to
determine the incidence and the association of intrathecal hydromorphone dose,
concentration, duration of treatment and concomitant agents with ICTG formation.
STUDY DESIGN: This is a retrospective analysis of 101 consecutive patients
implanted with intrathecal infusion delivery devices. Data were collected from
chart review, and records of pump refills from the division of Pain Medicine of
University Hospitals or outsourced to a home pump refill service. RESULTS: From a
cohort of 101 consecutively implanted patients, 69 were treated with intrathecal
hydromorphone and followed up postimplant for an average of 33.5 +/- 24 months
(range 0-93 months; 95% CI of 27-39 months). The incidence of ICTG in our patient
population was 8.7% during this period of time postimplant with mean time to
granuloma detection 35.1 +/- 7.9 months. Patients developing granuloma (n = 6)
were treated with a combination of intrathecal hydromorphone and bupivacaine
infusion. Exposure time to intrathecal agents was not different between the
granuloma and nongranuloma group. Monthly dose increase of hydromorphone was
higher in granuloma group vs. non-granuloma group (58 +/- 34 mcg/month n = 6 vs.
25 +/- 8 mcg/month n = 63). Four out of six granuloma cases occurred with low
dose and concentration of IT hydromorphone (160-370 mcg/day; 0.75-1.0 mg/mL
concentration). Intrathecal bupivacaine dose was not different between groups. A
subset of patients was treated with intrathecal fentanyl and bupivacaine. No
intrathecal granulomas occurred in this patient cohort. CONCLUSION: This is the
first clinical report demonstrating an association of hydromorphone with
intrathecal granulomas, particularly at low doses and concentrations of
hydromorphone. This study supports the notion that using low dose of IT opioids
might not protect against ICTG development but that the level of exposure and
type of opioid used in IT space might be highly correlated with ICTG development.
Further research and recommendations related to chronic intrathecal opioid
infusions are necessary to raise awareness of significant incidence of ICTG and
development of tests to isolate patient populations at high risk.
PMID- 27505060
TI - Nucleus Ruber of Actinopterygians.
AB - Nucleus ruber is known as an important supraspinal center that controls forelimb
movements in tetrapods, and the rubral homologue may serve similar functions in
fishes (motor control of pectoral fin). However, two apparently different
structures have been identified as 'nucleus ruber' in actinopterygians. One is
nucleus ruber of Goldstein (1905) (NRg), and the other nucleus ruber of
Nieuwenhuys and Pouwels (1983) (NRnp). It remains unclear whether one of these
nuclei (or perhaps both) is homologous to tetrapod nucleus ruber. To resolve this
issue from a phylogenetic point of view, we have investigated the distribution of
tegmental neurons retrogradely labeled from the spinal cord in eight
actinopterygian species. We also investigated the presence/absence of the two
nuclei with Nissl- or Bodian-stained brain section series of an additional 28
actinopterygian species by comparing the morphological features of candidate
rubral neurons with those of neurons revealed by the tracer studies. Based on
these analyses, the NRg was identified in all actinopterygians investigated in
the present study, while the NRnp appears to be absent in basal actinopterygians.
The phylogenetic distribution pattern indicates that the NRg is the more likely
homologue of nucleus ruber, and the NRnp may be a derived nucleus that emerged
during the course of actinopterygian evolution.
PMID- 27505061
TI - The impact of viscoplastic drops on a heated surface in the Leidenfrost regime.
AB - The impact morphology of viscoplastic drops on a heated surface in the
Leidenfrost regime is investigated experimentally by high-speed imaging. In
particular several important parameters which characterize the impact morphology
(such as maximum spreading diameter, minimum retracting diameter and maximum
bouncing height etc.) are measured by analysing the impact process, recorded
using a high-speed camera. It is shown that as the yield stress grows, surface
forces are no longer able to minimize the free surface of the drop, and the
inertial deformation upon impact becomes permanent. For small values of the yield
stress, the impact morphology of viscoplastic Leidenfrost drops is similar to
that of Newtonian drops. These effects can be interpreted in terms of the Bingham
Capillary number, which compares the yield stress magnitude and the capillary
(Laplace) pressure. These results suggest that the main contribution to drop
rebound is due to surface forces, and not to the intrinsic elasticity of the
vapour cushion between the drop and the surface, which is a major assumption in
one of the existing models.
PMID- 27505062
TI - Commensal Bacteria-Induced Inflammasome Activation in Mouse and Human Macrophages
Is Dependent on Potassium Efflux but Does Not Require Phagocytosis or Bacterial
Viability.
AB - Gut commensal bacteria contribute to the pathogenesis of inflammatory bowel
disease, in part by activating the inflammasome and inducing secretion of
interleukin-1beta (IL-1beta). Although much has been learned about inflammasome
activation by bacterial pathogens, little is known about how commensals carry out
this process. Accordingly, we investigated the mechanism of inflammasome
activation by representative commensal bacteria, the Gram-positive
Bifidobacterium longum subspecies infantis and the Gram-negative Bacteroides
fragilis. B. infantis and B. fragilis induced IL-1beta secretion by primary mouse
bone marrow-derived macrophages after overnight incubation. IL-1beta secretion
also occurred in response to heat-killed bacteria and was only partly reduced
when phagocytosis was inhibited with cytochalasin D. Similar results were
obtained with a wild-type immortalized mouse macrophage cell line but neither B.
infantis nor B. fragilis induced IL-1beta secretion in a mouse macrophage line
lacking the nucleotide-binding/leucine-rich repeat pyrin domain containing 3
(NLRP3) inflammasome. IL-1beta secretion in response to B. infantis and B.
fragilis was significantly reduced when the wild-type macrophage line was treated
with inhibitors of potassium efflux, either increased extracellular potassium
concentrations or the channel blocker ruthenium red. Both live and heat-killed B.
infantis and B. fragilis also induced IL-1beta secretion by human macrophages
(differentiated THP-1 cells or primary monocyte-derived macrophages) after 4
hours of infection, and the secretion was inhibited by raised extracellular
potassium and ruthenium red but not by cytochalasin D. Taken together, our
findings indicate that the commensal bacteria B. infantis and B. fragilis
activate the NLRP3 inflammasome in both mouse and human macrophages by a
mechanism that involves potassium efflux and that does not require bacterial
viability or phagocytosis.
PMID- 27505063
TI - Optimization of Non-Thermal Plasma Treatment in an In Vivo Model Organism.
AB - Non-thermal plasma is increasingly being recognized for a wide range of medical
and biological applications. However, the effect of non-thermal plasma on
physiological functions is not well characterized in in vivo model systems. Here
we use a genetically amenable, widely used model system, Drosophila melanogaster,
to develop an in vivo system, and investigate the role of non-thermal plasma in
blood cell differentiation. Although the blood system in Drosophila is primitive,
it is an efficient system with three types of hemocytes, functioning during
different developmental stages and environmental stimuli. Blood cell
differentiation in Drosophila plays an essential role in tissue modeling during
embryogenesis, morphogenesis and also in innate immunity. In this study, we
optimized distance and frequency for a direct non-thermal plasma application, and
standardized doses to treat larvae and adult flies so that there is no effect on
the viability, fertility or locomotion of the organism. We discovered that at
optimal distance, time and frequency, application of plasma induced blood cell
differentiation in the Drosophila larval lymph gland. We articulate that the
augmented differentiation could be due to an increase in the levels of reactive
oxygen species (ROS) upon non-thermal plasma application. Our studies open
avenues to use Drosophila as a model system in plasma medicine to study various
genetic disorders and biological processes where non-thermal plasma has a
possible therapeutic application.
PMID- 27505064
TI - Computer-Based Vertebral Tumor Cryoablation Planning and Procedure Simulation
Involving Two Cases Using MRI-Visible 3D Printing and Advanced Visualization.
AB - OBJECTIVE: We report the development and use of MRI-compatible and MRI-visible 3D
printed models in conjunction with advanced visualization software models to plan
and simulate safe access routes to achieve a theoretic zone of cryoablation for
percutaneous image-guided treatment of a C7 pedicle osteoid osteoma and an L1
lamina osteoblastoma. Both models altered procedural planning and patient care.
CONCLUSION: Patient-specific MRI-visible models can be helpful in planning
complex percutaneous image-guided cryoablation procedures.
PMID- 27505065
TI - Surface Enhanced Raman Scattering and Gated Materials for Sensing Applications:
The Ultrasensitive Detection of Mycoplasma and Cocaine.
AB - We present herein a novel combination of gated mesoporous silica nanoparticles
(MSNs) and surface-enhanced Raman scattering (SERS) for sensing applications. As
a proof-of-concept, we show the design of a system comprising MSNs loaded with
crystal violet (CV), a molecule with high Raman cross section acting as SERS
reporter, and capped with either a suitable DNA sequence for the detection of
Mycoplasma genomic DNA or with an aptamer that selectively coordinates cocaine.
In both cases the presence of the corresponding target analyte in solution (i.e.,
genomic DNA or cocaine) resulted in the release of CV. CV delivery was detected
by SERS upon adsorption on gold nanotriangles (AuNTs), which display an efficient
electromagnetic field enhancement and a high colloidal stability. By using this
novel procedure a limit of detection of at least 30 copies DNA per MUL was
determined for the detection of Mycoplasma genomic DNA, whereas cocaine was
detected at concentrations as low as 10 nm.
PMID- 27505066
TI - Why Are Nigeria-Cameroon Chimpanzees (Pan troglodytes ellioti) Free of SIVcpz
Infection?
AB - Simian immunodeficiency virus (SIV) naturally infects two subspecies of
chimpanzee: Pan troglodytes troglodytes from Central Africa (SIVcpzPtt) and P. t.
schweinfurtii from East Africa (SIVcpzPts), but is absent in P. t. verus from
West Africa and appears to be absent in P. t. ellioti inhabiting Nigeria and
western Cameroon. One explanation for this pattern is that P. t. troglodytes and
P. t schweinfurthii may have acquired SIVcpz after their divergence from P. t.
verus and P. t. ellioti. However, all of the subspecies, except P. t. verus,
still occasionally exchange migrants making the absence of SIVcpz in P. t.
ellioti puzzling. Sampling of P. t. ellioti has been minimal to date,
particularly along the banks of the Sanaga River, where its range abuts that of
P. t. troglodytes. This study had three objectives. First, we extended the
sampling of SIVcpz across the range of chimpanzees north of the Sanaga River to
address whether under-sampling might account for the absence of evidence for
SIVcpz infection in P. t. ellioti. Second, we investigated how environmental
variation is associated with the spread and prevalence of SIVcpz in the two
chimpanzee subspecies inhabiting Cameroon since environmental variation has been
shown to contribute to their divergence from one another. Finally, we compared
the prevalence and distribution of SIVcpz with that of Simian Foamy Virus (SFV)
to examine the role of ecology and behavior in shaping the distribution of
diseases in wild host populations. The dataset includes previously published
results on SIVcpz infection and SFVcpz as well as newly collected data, and
represents over 1000 chimpanzee fecal samples from 41 locations across Cameroon.
Results revealed that none of the 181 P. t. ellioti fecal samples collected
across the range of P. t. ellioti tested positive for SIVcpz. In addition,
species distribution models suggest that environmental variation contributes to
differences in the distribution and prevalence of SIVcpz and SFVcpz. The
ecological niches of these two viruses are largely non-overlapping, although
stronger statistical support for this conclusion will require more sampling.
Overall this study demonstrates that SIVcpz infection is absent or very rare in
P. t. ellioti, despite multiple opportunities for transmission. The reasons for
its absence remain unclear, but might be explained by one or more factors,
including environmental variation, viral competition, and/or local adaptation-all
of which should be explored in greater detail through continued surveillance of
this region.
PMID- 27505067
TI - Neutrophil Gelatinase-Associated Lipocalin as a Diagnostic Marker for Acute
Kidney Injury in Oliguric Critically Ill Patients: A Post-Hoc Analysis.
AB - BACKGROUND: Oliguria occurs frequently in critically ill patients, challenging
clinicians to distinguish functional adaptation from serum-creatinine-defined
acute kidney injury (AKIsCr). We investigated neutrophil gelatinase-associated
lipocalin (NGAL)'s ability to differentiate between these 2 conditions. METHODS:
This is a post-hoc analysis of a prospective cohort of adult critically ill
patients. Patients without oliguria within the first 6 h of admission were
excluded. Plasma and urinary NGAL were measured at 4 h after admission. AKIsCr
was defined using the AKI network criteria with pre-admission serum creatinine or
lowest serum creatinine value during the admission as the baseline value. Hazard
ratios for AKIsCr occurrence within 72 h were calculated using Cox regression and
adjusted for risk factors such as sepsis, pre-admission serum creatinine, and
urinary output. Positive predictive values (PPV) and negative predictive values
(NPV) were calculated for the optimal cutoffs for NGAL. RESULTS: Oliguria
occurred in 176 patients, and 61 (35%) patients developed AKIsCr. NGAL was a
predictor for AKIsCr in univariate and multivariate analysis. When NGAL was added
to a multivariate model including sepsis, pre-admission serum creatinine and
lowest hourly urine output, it outperformed the latter model (plasma p = 0.001;
urinary p = 0.048). Cutoff values for AKIsCr were 280 ng/ml for plasma (PPV 80%;
NPV 79%), and 250 ng/ml for urinary NGAL (PPV 58%; NPV 78%). CONCLUSIONS: NGAL
can be used to distinguish oliguria due to the functional adaptation from AKIsCr,
directing resources to patients more likely to develop AKIsCr.
PMID- 27505068
TI - A comparison of the response of two Burkholderia fungorum strains grown as
planktonic cells versus biofilm to dibenzothiophene and select polycyclic
aromatic hydrocarbons.
AB - In natural environments, bacteria often exist in close association with surfaces
and interfaces by establishing biofilms. Here, we report on the ability of
Burkholderia fungorum strains DBT1 and 95 to survive in high concentrations of
hydrocarbons, and we compare their growth as a biofilm vs. planktonic cells. The
2 compounds tested were dibenzothiophene (DBT) and a mixture of naphthalene,
phenanthrene, and pyrene (5:2:1) as representative compounds of thiophenes and
polycyclic aromatic hydrocarbons (PAHs), respectively. The results showed that
both strains were able to degrade DBT and to survive in the presence of up to a
2000 mg.L-1 concentration of this compound both as a biofilm and as free-living
cells. Moreover, B. fungorum DBT1 showed reduced tolerance towards the mixed PAHs
(2000 mg.L-1 naphthalene, 800 mg.L-1 phenanthrene, and 400 mg.L-1 pyrene) both as
a biofilm and as free-living cells. Conversely, biofilms of B. fungorum 95
enhanced resistance against these toxic compounds compared with planktonic cells
(P < 0.05). Visual observation through confocal laser scanning microscopy showed
that exposure of biofilms to DBT and PAHs altered their structure: high
concentrations of DBT triggered an aggregation of biofilm cells. These findings
provide new perspectives on the effectiveness of using DBT-degrading bacterial
strains in bioremediation of hydrocarbon-contaminated sites.
PMID- 27505069
TI - Grandparent involvement and children's health outcomes: The current state of the
literature.
AB - INTRODUCTION: Grandparents are often highly involved as secondary caregivers for
their grandchildren and may influence children's psychological and physical
health outcomes. The purpose of the current review was to gather and synthesize
research findings on the effects of grandparent involvement on children's
physical health outcomes. METHOD: PubMed, PsycInfo, and MedLine were searched by
3 independent reviewers for articles that reported on grandparent involvement and
children's health. Twenty-six articles were included for final review based on
selection criteria. RESULTS: Relatively few studies have examined the effects of
grandparent involvement on children's health outcomes; therefore, the degree of
their influence remains unclear. Four categories of children's health outcomes
(disease/illness, weight, eating behaviors, and injury/safety) emerged during
this review. Results indicated that the majority of studies available reported a
negative effect of grandparent involvement on child's weight status. However, it
is important to note that in most of these studies, the effects of grandparent
involvement were not a primary outcome, and the amount of time grandparents spent
with their grandchildren was not accounted for. Many studies in this review were
qualitative studies, limiting the types of analyses that could be conducted. In
addition, few longitudinal studies have been conducted in this area. DISCUSSION:
Based on this review, it is clear that grandparents are involved in caretaking
for children across many cultures but to understand their role in children's
health outcomes, more systematic and longitudinal research needs to be conducted.
(PsycINFO Database Record
PMID- 27505070
TI - Patient navigation to facilitate early intervention referral completion among
poor urban children.
AB - INTRODUCTION: Few eligible children participate in early intervention (EI)
programs. The objective of this study was to determine feasibility and outcomes
of a novel patient navigation program on EI referrals among a diverse group of at
risk children. METHODS: During a 6-month period, a patient navigator was assigned
to an urban pediatric clinic to engage families, provide education on early child
development and EI, and assist families with completing multidisciplinary
evaluations. Families were eligible to participate if they spoke English, had a
child <34 months old with a suspected developmental delay, and were referred to
EI for evaluation. Families completed measures of demographics, language
preference, and the Newest Vital Sign, a validated literacy measure. Outcomes on
completion of EI referrals were obtained from the county EI provider. RESULTS: Of
88 EI referrals during the study period, 53 patients were eligible and enrolled.
Patients were predominantly male, racially diverse, on public health insurance,
with a mean age of 18.4 months. Most caregivers of patients had less than a high
school education, spoke a non-English language at home, and had limited literacy.
Forty-two families (79.2%) completed a referral, and 34 (81.0%) of those were
eligible for EI services. There were no significant differences in demographic,
language, or literacy measures between those who completed and did not complete
EI referrals. DISCUSSION: A patient navigation program to facilitate EI referrals
was feasible in a diverse urban patient population. Preliminary results of the
patient navigation program on EI referral completion were promising and warrant
further study. (PsycINFO Database Record
PMID- 27505071
TI - Weight conversations in romantic relationships: What do they sound like and how
do partners respond?
AB - INTRODUCTION: The limited research examining weight conversations (i.e.,
conversations about weight, body shape, or size) in adult romantic relationships
has shown associations between engaging in these conversations and disordered
eating behaviors, overweight/obesity, and psychosocial problems in adults. Given
the potential harmful consequences of these conversations, it is important to
gather more rich qualitative data to understand how weight talk is experienced in
romantic relationships and how romantic partners respond to these conversations.
METHODS: Adults (n = 118; mean age 35 years) from a cross-sectional study were
interviewed in their homes. The majority of adults (90% female; mean age = 35
years) were from minority (64% African American) and low-income (<$25,000/year)
households. Qualitative data were analyzed using inductive content analysis.
RESULTS: Sixty-five percent of participants reported that weight conversations
were occurring in their romantic relationships. Qualitative themes included the
following: (a) Weight conversations were direct and focused on physical
characteristics; (b) weight conversations included joking or sarcastic remarks;
(c) weight conversations focused on "we" and being healthy; (d) weight
conversations occurred after watching TV or movies, as a result of insecurities
in oneself, as length of the relationship increased, or as partners aged; and (e)
partners responded to weight conversations by feeling insecure or by engaging in
reciprocal weight conversations with their romantic partner. DISCUSSION: Weight
conversations were prevalent in romantic relationships, with some conversations
experienced as negative and some positive. Qualitative themes from the current
study should be confirmed in quantitative studies to inform future intervention
research targeting weight conversations in romantic relationships. (PsycINFO
Database Record
PMID- 27505072
TI - Interview with Kaylene Simpson, PhD.
PMID- 27505073
TI - Electrophysiology-Based Assays to Detect Subtype-Selective Modulation of Human
Nicotinic Acetylcholine Receptors.
AB - The Family Smoking Prevention and Tobacco Control Act of 2009 (Public Law 111-31)
gave the US Food and Drug Administration (FDA) the responsibility for regulating
tobacco products. Nicotine is the primary addictive component of tobacco and its
effects can be modulated by additional ingredients in manufactured products.
Nicotine acts by mimicking the neurotransmitter acetylcholine on neuronal
nicotinic acetylcholine receptors (nAChRs), which function as ion channels in
cholinergic modulation of neurotransmission. Subtypes within the family of
neuronal nAChRs are defined by their alpha- and beta-subunit composition. The
subtype-selective profiles of tobacco constituents are largely unknown, but could
be essential for understanding the physiological effects of tobacco products. In
this report, we report the development and validation of electrophysiology-based
high-throughput screens (e-HTS) for human nicotinic subtypes, alpha3beta4,
alpha3beta4alpha5, alpha4beta2, and alpha7 stably expressed in Chinese Hamster
Ovary cells. Assessment of agonist sensitivity and acute desensitization gave
results comparable to those obtained by conventional manual patch clamp
electrophysiology assays. The potency of reference antagonists for inhibition of
the receptor channels and selectivity of positive allosteric modulators also were
very similar between e-HTS and conventional manual patch voltage clamp data.
Further validation was obtained in pilot screening of a library of FDA-approved
drugs that identified alpha7 subtype-selective positive allosteric modulation by
novel compounds. These assays provide new tools for profiling of nicotinic
receptor selectivity.
PMID- 27505074
TI - Analytical Characteristics of a Noninvasive Gene Expression Assay for Pigmented
Skin Lesions.
AB - We previously reported clinical performance of a novel noninvasive and
quantitative PCR (qPCR)-based molecular diagnostic assay (the pigmented lesion
assay; PLA) that differentiates primary cutaneous melanoma from benign pigmented
skin lesions through two target gene signatures, LINC00518 (LINC) and
preferentially expressed antigen in melanoma (PRAME). This study focuses on
analytical characterization of this PLA, including qPCR specificity and
sensitivity, optimization of RNA input in qPCR to achieve a desired diagnostic
sensitivity and specificity, and analytical performance (repeatability and
reproducibility) of this two-gene PLA. All target qPCRs demonstrated a good
specificity (100%) and sensitivity (with a limit of detection of 1-2 copies),
which allows reliable detection of gene expression changes of LINC and PRAME
between melanomas and nonmelanomas. Through normalizing RNA input in qPCR, we
converted the traditional gene expression analyses to a binomial detection of
gene transcripts (i.e., detected or not detected). By combining the binomial qPCR
results of the two genes, an improved diagnostic sensitivity (raised from 52%-
65% to 71% at 1 pg of total RNA input, and to 91% at 3 pg of total RNA input) was
achieved. This two-gene PLA demonstrates a high repeatability and reproducibility
(coefficient of variation <3%) and all required analytical performance
characteristics for the commercial processing of clinical samples.
PMID- 27505075
TI - Adaptive Benefits of Storage Strategy and Dual AMPK/TOR Signaling in Metabolic
Stress Response.
AB - Cellular metabolism must ensure that supply of nutrient meets the biosynthetic
and bioenergetic needs. Cells have therefore developed sophisticated signaling
and regulatory pathways in order to cope with dynamic fluctuations of both
resource and demand and to regulate accordingly diverse anabolic and catabolic
processes. Intriguingly, these pathways are organized around a relatively small
number of regulatory hubs, such as the highly conserved AMPK and TOR kinase
families in eukaryotic cells. Here, the global metabolic adaptations upon dynamic
environment are investigated using a prototypical model of regulated metabolism.
In this model, the optimal enzyme profiles as well as the underlying regulatory
architecture are identified by combining perturbation and evolutionary methods.
The results reveal the existence of distinct classes of adaptive strategies,
which differ in the management of storage reserve depending on the intensity of
the stress and in the regulation of ATP-producing reaction depending on the
nature of the stress. The regulatory architecture that optimally implements these
adaptive features is characterized by a crosstalk between two specialized
signaling pathways, which bears close similarities with the sensing and
regulatory properties of AMPK and TOR pathways.
PMID- 27505076
TI - Modes of Large-Scale Brain Network Organization during Threat Processing and
Posttraumatic Stress Disorder Symptom Reduction during TF-CBT among Adolescent
Girls.
AB - Posttraumatic stress disorder (PTSD) is often chronic and disabling across the
lifespan. The gold standard treatment for adolescent PTSD is Trauma-Focused
Cognitive-Behavioral Therapy (TF-CBT), though treatment response is variable and
mediating neural mechanisms are not well understood. Here, we test whether PTSD
symptom reduction during TF-CBT is associated with individual differences in
large-scale brain network organization during emotion processing. Twenty
adolescent girls, aged 11-16, with PTSD related to assaultive violence completed
a 12-session protocol of TF-CBT. Participants completed an emotion processing
task, in which neutral and fearful facial expressions were presented either
overtly or covertly during 3T fMRI, before and after treatment. Analyses focused
on characterizing network properties of modularity, assortativity, and global
efficiency within an 824 region-of-interest brain parcellation separately during
each of the task blocks using weighted functional connectivity matrices. We
similarly analyzed an existing dataset of healthy adolescent girls undergoing an
identical emotion processing task to characterize normative network organization.
Pre-treatment individual differences in modularity, assortativity, and global
efficiency during covert fear vs neutral blocks predicted PTSD symptom reduction.
Patients who responded better to treatment had greater network modularity and
assortativity but lesser efficiency, a pattern that closely resembled the control
participants. At a group level, greater symptom reduction was associated with
greater pre-to-post-treatment increases in network assortativity and modularity,
but this was more pronounced among participants with less symptom improvement.
The results support the hypothesis that modularized and resilient brain
organization during emotion processing operate as mechanisms enabling symptom
reduction during TF-CBT.
PMID- 27505077
TI - PCNA SUMOylation protects against PCNA polyubiquitination-mediated, Rad59
dependent, spontaneous, intrachromosomal gene conversion.
AB - Homologous recombination is crucial in both the maintenance of genome stability
and the generation of genetic diversity. Recently, multiple aspects of the
recombination machinery functioning at arrested DNA replication forks have been
established, yet the roles of diverse modifications of PCNA, the key platform
organizing the replication complex, in intrachromosomal recombination have not
been comprehensively elucidated. Here, we report how PCNA SUMOylation and/or
polyubiquitination affects recombination between direct repeats in S. cerevisiae.
Our results show that these PCNA modifications primarily affect gene conversion,
whereas their effect on the recombination-mediated deletion of intervening
sequence is much less obvious. Siz1-dependent PCNA SUMOylation strongly limits
Rad52/Rad51/Rad59-dependent gene conversion. A 5- to 10-fold increase in the
frequency of such recombination events is observed in Siz1-defective strains, but
this increase is fully suppressed when PCNA polyubiquitination is also
compromised. PCNA polyubiquitination can stimulate gene conversion in both PCNA
SUMOylation-proficient and SUMOylation-deficient strains. On the other hand, in
PCNA polyubiquitination-deficient strains, the lack of PCNA SUMOylation does not
affect GC levels. Therefore, we postulate that the antirecombinogenic activity of
Siz1 mainly concerns recombination induced by PCNA polyubiquitination. In the
absence of PCNA SUMOylation, the frequency of PCNA polyubiquitination-mediated
gene conversion is not only increased, but it is also channeled into the Rad59
dependent pathway. Additionally, we show a weak inhibitory effect of Rad5 on
Rad52/Rad59-directed single-strand annealing.
PMID- 27505078
TI - Multi-inhibitor prodrug constructs for simultaneous delivery of anti-inflammatory
agents to mustard-induced skin injury.
AB - The molecular pathology of sulfur mustard injury is complex, with at least nine
inflammation-related enzymes and receptors upregulated in the zone of the insult.
A new approach wherein inhibitors of these targets have been linked by
hydrolyzable bonds, either one to one or via separate preattachment to a carrier
molecule, has been shown to significantly enhance the therapeutic response
compared with the individual agents. This article reviews the published work of
the authors in this drug development domain over the last 8 years.
PMID- 27505079
TI - Delayed diagnosis of single compartment muscle contusion after radical
hysterectomy in the lithotomy position: A case report.
AB - INTRODUCTION: Muscle contusions usually occur as a result of blunt trauma, which
damages the muscle fibers and connective tissue without breaking the skin. Rapid
bleeding can cause an increase in pressure that requires surgical intervention,
commonly referred to as compartment syndrome. Here, we report a case with delayed
diagnosis of single compartment muscle contusion in which compartment syndrome
did not develop. PRESENTATION OF CASE: A 50-year-old woman underwent radical
hysterectomy. She complained of edema and tenderness in the lower left leg on
postoperative day 6. The serum creatine phosphokinase level was slightly elevated
at 177 IU/L (normal range: 6-142 IU/L). T2-weighted magnetic resonance imaging
revealed swelling of the muscle in the deep posterior compartment of the lower
left leg, edematous fascia, and subcutaneous adipose tissue. She recovered
naturally without other complications. DISCUSSION: In the lithotomy position
during surgery, muscle contusion might occur, without general symptoms.
CONCLUSION: Magnetic resonance imaging is useful for diagnosis. For patients who
complain of edema and tenderness in the lower leg after surgery in the lithotomy
position, muscle contusions should be considered.
PMID- 27505080
TI - Hyperfunctioning papillary thyroid carcinoma: A case report with literature
review.
AB - INTRODUCTION: Thyroid malignant tumors are rarely associated with
hyperfunctioning thyroid. The incidence of this co-incidence is highly variable.
Here we report a rare case of papillary thyroid cancer associated with
hyperthyroidism with brief literature review. CASE REPORT: A 40-year-old male,
presented with palpitation, excess sweating and weight loss for one month
duration. There was asymmetrical swelling of the neck, more on right side,
mobile. Free T3: 11.09pmol/L, free T4: 34.41pmol/L, TFT: less than 0.005mIU/ml,
Neck ultrasound showed features of background thyroiditis. Left lobe contained
9*7*5mm nodule with irregular outline and multiple dots of calcification, other
nodules are of the same features. Under ultrasound guide, fine needle aspiration
cytology showed features of papillary carcinoma. After preparation, total
thyrodectomy done and the result of histopathological examination confirmed
papillary thyroid carcinoma. The patient was put on 0.2mg thyroxine daily.
DISCUSSION: Literature review has showed an increasing number of papers reporting
the association of high level of thyroid function tests and thyroid malignancy.
The cause of high level of TH in thyroid malignancy is thought to be due to an
active mutation of the gene of TH receptor. Niepomniszcze and colleagues found
that a combination of TSH receptor mutations and Ki-RAS was the main etiological
factor for hyperfunction of the thyroid malignancy. CONCLUSION: Although the
coexistence of them is rare, thyroid malignancy should be put in the differential
diagnosis of hyperthyroid goiter.
PMID- 27505081
TI - High-frequency operation of a pulsatile VAD - a simulation study.
AB - Ventricular assist devices (VADs) are mechanical blood pumps that are clinically
used to treat severe heart failure. Pulsatile VADs (pVADs) were initially used,
but are today in most cases replaced by turbodynamic VADs (tVADs). The major
concern with the pVADs is their size, which prohibits full pump body implantation
for a majority of patients. A reduction of the necessary stroke volume can be
achieved by increasing the stroke frequency, while maintaining the same level of
support capability. This reduction in stroke volume in turn offers the
possibility to reduce the pump's overall dimensions. We simulated a human
cardiovascular system (CVS) supported by a pVAD with three different stroke rates
that were equal, two- or threefold the heart rate (HR). The pVAD was additionally
synchronized to the HR for better control over the hemodynamics and the
ventricular unloading. The simulation results with a HR of 90 bpm showed that a
pVAD stroke volume can be reduced by 71%, while maintaining an aortic pulse
pressure (PP) of 30 mm Hg, avoiding suction events, reducing the ventricular
stroke work (SW) and allowing the aortic valve to open. A reduction by 67% offers
the additional possibility to tune the interaction between the pVAD and the CVS.
These findings allow a major reduction of the pVAD's body size, while allowing
the physician to tune the pVAD according to the patient's needs.
PMID- 27505082
TI - Shear stress and von Mises stress distributions in the periphery of an embedded
acetabular cup implant during impingement.
AB - As literature implies, daily activities of total hip arthroplasty (THA) patients
may include movements prone to implant-implant impingement. Thus, high shear
stresses may be induced at the acetabular implant-bone interface, increasing the
risk of implant loosening. The aim of the current study is to determine whether
or not impingement events may pose an actual risk to acetabular periprosthetic
bone. An existing experimental workflow was augmented to cover complete three
dimensional strain gage measurement. von Mises and shear stresses were calculated
from 1620 measured strain values, collected around a hemispherical cup implant at
2.5 mm interface distance during worst-case impingement loading. A shear stress
criterion for acetabular periprosthetic bone was derived from the literature. At
the impingement site, magnitudes of von Mises stress amount to 0.57 MPa and
tilting shear stress amount to -0.3 MPa at 2.5 mm interface distance. Conclusion
can be drawn that worst-case impingement events are unlikely to pose a risk of
bone material failure in the periphery around fully integrated cementless
acetabular hip implants in otherwise healthy THA patients. As numerical
predictions in the literature suggested, it can now be confirmed that impingement
moments are unlikely to cause acetabular implant-bone interface fixation
failures.
PMID- 27505083
TI - Hematological changes in severe early onset growth-restricted fetuses with absent
and reversed end-diastolic flow in the umbilical artery.
AB - BACKGROUND: Erythropoietin seems to play an important role in the regulation of
fetal hypoxemia. The present prospective study was designed to determine if
changes in erythropoietin levels can be found in fetuses with severe early-onset
growth restriction and hemodynamic compromise. METHODS AND RESULTS:
Erythropoietin, hemoglobin, hematocrit, platelet counts, normoblasts, lacate,
arterial and venous blood gasses in the umbilical cord were determined in 42
fetuses with fetal growth restriction (IUGR) with absent (zero-flow) and 26 IUGR
fetuses with retrograde end-diastolic flow (reverse-flow) in the umbilical
artery. Color Doppler measurements were performed on the middle cerebral artery
(PI) and ductus venosus [(S-a)/D and (S-a)/Vmean]. Erythropoietin concentrations
were significantly lower in the zero-flow group (median: 128.0 mU/mL; range: 60.3
213 mU/mL) compared with the reverse-flow group (median: 202.5 mU/mL; range: 166
1182 mU/mL). Significant differences in median lactate concentrations were
observed between the zero-flow group: 3.28 mmol/L (range; 2.3-4.7 mmol/L), and
reverse-flow group: 5.6 mmol/L (range: 3.8-7.5 mmol/L). Fetuses with reverse-flow
had significantly lower median platelet counts than fetuses with zero-flow (74
vs. 155/MUL) and significantly lower normoblast counts (63 vs. 342/100 WBC).
CONCLUSIONS: Fetuses with severe IUGR due to chronic placental insufficiency and
absent or reversed flow in the umbilical artery show increased erythropoietin
levels.
PMID- 27505084
TI - Is vaping a gateway to smoking: a review of the longitudinal studies.
AB - BACKGROUND: The use of e-cigarettes (ECs) is rising globally. There is concern
that e-cigarette may actually lead to smoking, especially amongst adolescents.
OBJECTIVE: To perform a comprehensive review of literature reporting the
longitudinal effects of e-cigarette use on onset of smoking among adolescents and
young adults. METHODS: A search was conducted using PubMed, Google Scholar,
Scopus, and Web of Science in February 2016 to identify the studies containing
data on EC use among adolescents and young adults (age<30 years). We then
narrowed our search to only include longitudinal studies with data on EC and
conventional cigarette smoking among this population. RESULTS: Four longitudinal
studies were identified that analyzed the use of ECs and smoking at both baseline
and follow-ups in the target population. These studies demonstrated that EC use
is associated with an increase in combustible cigarette smoking, even amongst the
adolescents who were not susceptible to smoking. CONCLUSION: This review
highlights the strong evidence that not only are ECs are not an effective tool
for smoking cessation among adolescents, they actually are associated with higher
incidence of combustible cigarette smoking. Policy makers need to recognize of
the insidious nature of this campaign by the tobacco industry and design policies
to regulate it.
PMID- 27505085
TI - Integrated oral, mental and sexual health management for adolescents: a call for
professional collaboration.
AB - BACKGROUND: Globally, young people account for 15.5% of the total global
disability-adjusted life-years burden for all age groups. They face mental
health, nutritional problems, accidental and intentional injuries, sexual and
reproductive health problems, and substance abuse. These health challenges have
effects on their oral health. This paper discusses the oral health problems
adolescents face and suggests approaches for providing integrated oral and
general health care for adolescents. DISCUSSION: Oral health issues linked with
adolescent health concerns include: malocclusion and esthetic concerns linked
with mental health status; oral and maxillofacial injuries linked with accidental
and intentional injuries; oral manifestations of sexually transmitted infections;
oral leukoplakia and oral cancers linked with alcohol, tobacco and psychoactive
substance abuse; and oral manifestations of anemia resulting from nutritional
problems. Training oral health care providers on adolescent health and care could
promote prompt diagnosis, management and prevention of complications associated
with major health challenges affecting adolescents. CONCLUSION: Adolescent oral
health care needs focused attention: as a possible route for early diagnosis and
management of general health problems and for promoting adolescent oral health
care. Oral health care should be integrated into adolescent friendly services and
oral health care providers should learn how to handle adolescents' health needs.
PMID- 27505086
TI - A novel insulin receptor mutation in an adolescent with acanthosis nigricans and
hyperandrogenism.
AB - Insulin receptor mutations cause extreme insulin resistance resulting in
acanthosis nigricans and hyperandrogenism. We report a pre-menarchal adolescent
female with normal weight, with severe acanthosis nigricans, acne, and hirsutism.
Initial investigation revealed elevated fasting and post-prandial insulin and
high testosterone and androstenedione levels. Her father had frequent complaints
of hypoglycemia. Coding sequence and splice junction analysis of the INSR gene,
in our patient and her father, revealed a heterozygous missense mutation in the
beta subunit of the insulin receptor (Arg1131Trp), resulting in receptor loss of
function. Metformin therapy and carbohydrate control improved acanthosis and
menarche ensued within 3 months. Our case highlights the importance of
distinguishing insulin resistance commonly associated with obesity from monogenic
defects. Although, there is no consensus on treatment of children with monogenic
forms of insulin resistance due to its rarity, dietary and lifestyle
modifications and insulin-sensitizing agents play a key role in management.
PMID- 27505087
TI - Biological evaluation and docking studies of some benzoxazole derivatives as
inhibitors of acetylcholinesterase and butyrylcholinesterase.
AB - A series of 2,5-disubstituted-benzoxazole derivatives (1-13) were evaluated as
possible inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase
(BChE). The results demonstrated that the compounds exhibited a broad spectrum of
AChE and BChE inhibitory activity ranging between 6.80% and 90.21% except one
compound which showed no activity against AChE at the specified molar
concentration. Another derivative displayed a similar activity to that of
reference drug (galanthamine) for inhibition of AChE and BChE. In addition,
molecular docking of the compounds into active site of AChE was performed using
recombinant human AChE (PDB ID: 4ey6) in order to understand ligand-protein
interactions.
PMID- 27505088
TI - Highlight: annexins in health and disease.
PMID- 27505089
TI - Development of a rapid and quantitative lateral flow assay for the simultaneous
measurement of serum kappa and lambda immunoglobulin free light chains (FLC):
inception of a new near-patient FLC screening tool.
AB - BACKGROUND: Serum free light chains (FLC) are sensitive biomarkers used for the
diagnosis and management of plasma cell dyscrasias, such as multiple myeloma
(MM), and are central to clinical screening algorithms and therapy response
criteria. We have developed a portable, near-patient, lateral-flow test
(Seralite(r)) that quantitates serum FLC in 10 min, and is designed to eliminate
sample processing delays and accelerate decision-making in the clinic. METHODS:
Assay interference, imprecision, lot-to-lot variability, linearity, and the
utility of a competitive-inhibition design for the elimination of antigen-excess
('hook effect') were assessed. Reference ranges were calculated from 91 healthy
donor sera. Preliminary clinical validation was conducted by retrospective
analysis of sera from 329 patients. Quantitative and diagnostic results were
compared to Freelite(r). RESULTS: Seralite(r) gave a broad competitive-inhibition
calibration curve from below 2.5 mg/L to above 200 mg/L, provided good assay
linearity (between 1.6 and 208.7 mg/L for kappa FLC and between 3.5 and 249.7
mg/L for lambda FLC) and sensitivity (1.4 mg/L for kappa FLC and 1.7 mg/L for
lambda FLC), and eliminated anomalous results from antigen-excess. Seralite(r)
gave good diagnostic concordance with Freelite(r) (Roche Hitachi Cobas C501)
identifying an abnormal FLC ratio and FLC difference in 209 patients with newly
diagnosed MM and differentiating these patients from normal healthy donors with
polyclonal FLC. CONCLUSIONS: Seralite(r) sensitively quantitates FLC and rapidly
identifies clinical conditions where FLC are abnormal, including MM.
PMID- 27505091
TI - How can we evaluate differences between serial measurements on the same sample? A
new approach based on within-subject biological variation.
PMID- 27505090
TI - Pediatric reference intervals for alkaline phosphatase.
AB - BACKGROUND: Interpretation of alkaline phosphatase activity in children is
challenging due to extensive changes with growth and puberty leading to distinct
sex- and age-specific dynamics. Continuous percentile charts from birth to
adulthood allow accurate consideration of these dynamics and seem reasonable for
an analyte as closely linked to growth as alkaline phosphatase. However, the
ethical and practical challenges unique to pediatric reference intervals have
restricted the creation of such percentile charts, resulting in limitations when
clinical decisions are based on alkaline phosphatase activity. METHODS: We
applied an indirect method to generate percentile charts for alkaline phosphatase
activity using clinical laboratory data collected during the clinical care of
patients. A total of 361,405 samples from 124,440 patients from six German
tertiary care centers and one German laboratory service provider measured between
January 2004 and June 2015 were analyzed. Measurement of alkaline phosphatase
activity was performed on Roche Cobas analyzers using the IFCC's photometric
method. RESULTS: We created percentile charts for alkaline phosphatase activity
in girls and boys from birth to 18 years which can be used as reference
intervals. Additionally, data tables of age- and sex-specific percentile values
allow the incorporation of these results into laboratory information systems.
CONCLUSIONS: The percentile charts provided enable the appropriate differential
diagnosis of changes in alkaline phosphatase activity due to disease and changes
due to physiological development. After local validation, integration of the
provided percentile charts into result reporting facilitates precise assessment
of alkaline phosphatase dynamics in pediatrics.
PMID- 27505092
TI - Therapeutic decision-making process in the intensive care unit: role of
biological point-of-care testing.
PMID- 27505093
TI - Thiol/disulfide parameters as a novel oxidative marker in medical labor induction
with oxytocin.
AB - BACKGROUND: The aim of this study was to analyze the alterations in thiol levels
among mothers and neonates who were prone to medical oxytocin induction.
MATERIALS AND METHODS: A total of 40 pregnant women who underwent medical labor
induction with oxytocin (Group A) were compared with 53 women whose labor
progressed spontaneously without any kind of induction (Group B). We measured the
thiol/disulfide homeostasis parameters (native thiol, total thiol, disulfide,
disulfide/total thiol, disulfide/native thiol) of maternal and cord blood.
RESULTS: There were no statistically significant differences with respect to the
maternal and cord blood thiol/disulfide homeostasis between the two groups.
CONCLUSION: Being an artificial intervention during labor, oxytocin induction has
been found to be safe in terms of oxidative stress (OS) according to the results
of this study. Both the maternal and the fetal sides were safe in this molecular
manner against oxytocin infusion.
PMID- 27505095
TI - Bcl-2 family proteins: master regulators of cell survival.
AB - The most prominent function of proteins of the Bcl-2 family is regulation of the
initiation of intrinsic (mitochondrial) pathways of apoptosis. However, recent
research has revealed that in addition to regulation of mitochondrial apoptosis,
proteins of the Bcl-2 family play important roles in regulating other cellular
pathways with a strong impact on cell survival like autophagy, endoplasmic
reticulum (ER) stress response, intracellular calcium dynamics, cell cycle
progression, mitochondrial dynamics and energy metabolism. This review summarizes
the recent knowledge about functions of Bcl-2 family proteins that are related to
cell survival.
PMID- 27505094
TI - Alzheimer's disease: presence and role of microRNAs.
AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that
accounts for the most cases of dementia. AD affects more than 25 million people
globally and is predicted to affect nearly one in 85 people worldwide by 2050. AD
is characterized by the accumulation of dense plaques of beta-amyloid peptide
(Abeta) and neurofibrillary tangles of hyperphosphorylated tau that cause
impairment in memory, cognition, and daily activities. Although early-onset AD
has been linked to several mutations, reliable genetic markers for late-onset AD
are lacking. Further, the diagnosis of AD biomarkers has its limitations and
cannot detect early-stage AD. The identification of accurate, early, and non
invasive biomarkers for AD is, therefore, an unmet challenge. Recently, microRNAs
(miRNAs) have emerged as a novel class of gene regulatory elements with conserved
roles in development and disease. Recent discoveries have uncovered roles of
miRNAs in several model organisms during aging and have identified potential
miRNAs biomarkers of AD. Here we will discuss this emerging field of miRNAs
associated with AD and prospects for the future.
PMID- 27505096
TI - An observational study of secondary task engagement while driving on urban
streets in Iranian Safe Communities.
AB - In Iran the prevalence of traffic injuries and death from vehicle collisions are
high. Driver engagement in non-driving-related tasks has been previously
identified as an important contributing factor to crashes. Therefore, the
objective of the present study was to investigate the prevalence of drivers'
engagement in potentially distracting activities in Kashmar, Khalilabad and
Bardaskan, which are three Iranian International Safe Communities. Observations
took place at 12 randomly selected roadside locations in each city, which were
comprised of six main streets and six side streets. In total 7979 drivers were
observed. The prevalence rates of potentially distracting activities in Kashmar,
Khalilabad and Bardaskan were 24.3%, 26% and 24.9%, respectively. In both Kashmar
and Khalilabad the most frequently observed secondary tasks were drivers talking
to passengers (10.6% and 11.5%, respectively) followed by mobile phone use (3.4%
and 4.0%, respectively). Although in Bardaskan the most commonly observed
secondary task was also talking to passengers (12.7%), the second most common was
reaching for an object (3.2%). In all three cities younger drivers were
significantly more likely to be observed engaged in a secondary task while
driving. Furthermore, involvement in secondary tasks while driving was
significantly higher amongst females and those driving on a working day. The
percentage of drivers identified as potentially distracted in these three Safe
Communities was worryingly high. Thus, interventions should be integrated into
the WHO Safe Community network in these cities, including: education regarding
the risks associated with engaging in secondary activities while driving, law
enforcement, tougher legislation, periodic assessment, raising public awareness,
as well as attracting political and social support.
PMID- 27505097
TI - Role of sensory and cognitive conspicuity in the prevention of collisions between
motorcycles and trucks at T-intersections.
AB - Motorcyclists are particularly vulnerable to injury in crashes with heavy
vehicles due to substantial differences in vehicle mass, the degree of protection
and speed. There is a considerable difference in height between motorcycles and
trucks; motorcycles are viewed by truck drivers from downward angles, and shorter
distances between them mean steeper downward angles. Hence, we anticipated that
the effects of motorcycle conspicuity treatments would be different for truck
drivers. Therefore, this study aims to evaluate the effects of motorcycle
conspicuity treatments on the identification and detection of motorcycles by
truck drivers. Two complementary experiments were performed; the first experiment
assessed the impact of motorcycle sensory conspicuity on the ability of un
alerted truck drivers to detect motorcycles, and the second experiment assessed
the motorcycle cognitive conspicuity to alerted truck drivers. The sensory
conspicuity was measured in terms of motorcycle detection rates by un-alerted
truck drivers when they were not anticipating a motorcycle within a realistic
driving scene, while the cognitive conspicuity was determined by the time taken
by alerted truck drivers to actively search for a motorcycle. In the first
experiment, the participants were presented with 10 pictures and were instructed
to report the kinds of vehicles that were presented in the pictures. Each picture
was shown to the participants for 600ms. In the second experiment, the
participants were presented with the same set of pictures and were instructed to
respond by clicking the right button on a mouse as soon as they detected a
motorcycle in the picture. The results indicate that the motorcycle detection
rate increases, and the response time to search for a motorcycle decreases, as
the distance between the targeted motorcycle and the viewer decreases. This is
true regardless of the type of conspicuity treatment used. The use of daytime
running headlights (DRH) was found to increase the detection rate and the
identification of a motorcycle by a truck driver at a farther distance, but
effect deteriorates as the distance decreases. The results show that the
detection rate and the identification of a motorcyclist wearing a black helmet
with a reflective sticker increases as the distance between the motorcycle and
the truck decreases. We also found that a motorcyclist wearing a white helmet and
a white outfit is more identifiable and detectable at both shorter and longer
distances. In conclusion, although this study provides evidence that the use of
appropriate conspicuity treatments enhances motorcycle conspicuity to truck
drivers, we suggest that more attention should be paid to the effect of
background environment on motorcycle conspicuity.
PMID- 27505098
TI - Exploring factors affecting pedestrians' red-light running behaviors at
intersections in China.
AB - Pedestrians' Red-light running behavior is one of the most critical factors for
pedestrian involved traffic crashes at intersections in China. The primary
objective of this study is to explore how various factors affect pedestrians' red
light running behaviors at intersection areas, using the data collected from
Hefei, China. A questionnaire was well designed aiming at collecting pedestrians'
socio-economic characteristics, trip related features, and attribute variables in
different crossing facilities. Based on 631 valid samples, a binomial logistic
model was established to evaluate the impacts of contributing factors on
pedestrians' red-light running behavior. The modeling results show that four
variables significantly affect the probability of pedestrians' red-light running
behavior, which are the trip purpose, time period in one day, pedestrian's
attitude towards whether to run a red light when in hurry, and pedestrian's
attitude towards whether quality of road facility affects crossing behavior. With
those variables, the probability of pedestrians' red-light running behavior at
intersections could be predicted. Findings of this study can help understand why
pedestrians in China run red-lights and identify which pedestrian groups and
intersections are more likely to have such behaviors. This study can also help
propose countermeasures more efficiently to reduce pedestrian-related crashes at
intersections in China.
PMID- 27505099
TI - Examining driver injury severity outcomes in rural non-interstate roadway crashes
using a hierarchical ordered logit model.
AB - Rural non-interstate crashes induce a significant amount of severe injuries and
fatalities. Examination of such injury patterns and the associated contributing
factors is of practical importance. Taking into account the ordinal nature of
injury severity levels and the hierarchical feature of crash data, this study
employs a hierarchical ordered logit model to examine the significant factors in
predicting driver injury severities in rural non-interstate crashes based on two
year New Mexico crash records. Bayesian inference is utilized in model estimation
procedure and 95% Bayesian Credible Interval (BCI) is applied to testing variable
significance. An ordinary ordered logit model omitting the between-crash variance
effect is evaluated as well for model performance comparison. Results indicate
that the model employed in this study outperforms ordinary ordered logit model in
model fit and parameter estimation. Variables regarding crash features,
environment conditions, and driver and vehicle characteristics are found to have
significant influence on the predictions of driver injury severities in rural non
interstate crashes. Factors such as road segments far from intersection, wet road
surface condition, collision with animals, heavy vehicle drivers, male drivers
and driver seatbelt used tend to induce less severe driver injury outcomes than
the factors such as multiple-vehicle crashes, severe vehicle damage in a crash,
motorcyclists, females, senior drivers, driver with alcohol or drug impairment,
and other major collision types. Research limitations regarding crash data and
model assumptions are also discussed. Overall, this research provides reasonable
results and insight in developing effective road safety measures for crash injury
severity reduction and prevention.
PMID- 27505100
TI - How rare are large, multiple-fatality work-related incidents?
AB - Despite their salience, the prevalence of incidents that result in many work
related deaths is not well-documented. This study estimated probabilities of
observing large scale work-related fatal incidents using 1995-2010 records from
the Census of Fatal Occupational Injuries. A range of model estimates suggest
approximately a one-in-four annual chance of observing an incident resulting in
20 or more work-related fatalities. The most likely contributors are aircraft
incidents, and fires and explosions. The probability that a large scale incident
occurs has declined in recent years due to a general decline in the number of
fatal incidents, and due to a compositional shift away from those types of
incidents more likely to result in large scale outcomes.
PMID- 27505101
TI - Light-Triggered Release from Pickering Emulsions Stabilized by TiO2 Nanoparticles
with Tailored Wettability.
AB - In this work, a new strategy for developing light-triggered Pickering emulsions
as smart soft vehicles for on-demand release is proposed. Initially, UV-induced
tailored wettability allows anchoring of TiO2 nanoparticles at the interface to
prepare stable water in oil emulsions. Such emulsions show the efficacy of
microencapsulation and controlled release by demulsification due to the
hydrophilic conversion of the TiO2 nanoparticles using a noninvasive light
irradiation trigger. A molecule of interest is selected as a model cargo to
quantitatively evaluate the as-prepared Pickering emulsions for their
encapsulation and release behaviors. Moreover, light-responsive emulsion
destabilization mechanism is studied as a function of particle concentration,
light wavelength, and light intensity, respectively, determined by drop diameter
evolution and droplet coalescence kinetics plots. For consideration of
application in life sciences, Pickering emulsions sensitive to visible light are
also established based on nitrogen doping of TiO2 nanoparticle emulsifiers.
PMID- 27505105
TI - Long-Term Outcome of Nephron-Sparing Surgery Compared to Radical Nephrectomy for
Renal Cell Carcinoma >=4 cm - A Matched-Pair Single Institution Analysis.
AB - PURPOSE: We investigated the long-term oncological and functional outcome of
nephron-sparing surgery/partial nephrectomy (PN) versus radical nephrectomy (RN)
for any renal cell carcinoma (RCC) >=4 cm. PATIENTS AND METHODS: Between 1997 and
2013, we identified 128 patients undergoing PN for RCC >=4 cm and matched this
collective to 128 patients undergoing RN. We then compared overall survival (OS),
cancer-specific survival (CSS), progression-free survival (PFS) and functional
parameters in both groups. The median follow-up time was 58 months (3-210
months). RESULTS: Compared to RN, patients with a PN showed a significantly
higher 10-year OS (77.0 vs. 63.0%, p = 0.04), CSS (90.6 vs. 71.7%, p = 0.002) and
PFS (82.9 vs. 57.4%, p <= 0.001). Renal function preservation was better in the
PN group (24 months estimated glomerular filtration rate: 68.2 ml/min for PN vs.
40.6 ml/min for RN, p <= 0.01) with significantly less new onset chronic kidney
diseases. Total complication rate was comparable, whereas PN procedures showed
more Clavien-Dindo grade I + II complications, portraying the technical challenge
of PN in larger RCCs. CONCLUSIONS: Whenever feasible, PN should be considered for
renal masses >=4 cm, as this technique shows better long-term results regarding
disease-specific survival and renal function preservation in our study group.
PMID- 27505107
TI - Computational Design of Non-natural Sugar Alcohols to Increase Thermal Storage
Density: Beyond Existing Organic Phase Change Materials.
AB - Thermal storage, a technology that enables us to control thermal energy, makes it
possible to reuse a huge amount of waste heat, and materials with the ability to
treat larger thermal energy are in high demand for energy-saving societies. Sugar
alcohols are now one promising candidate for phase change materials (PCMs)
because of their large thermal storage density. In this study, we computationally
design experimentally unknown non-natural sugar alcohols and predict their
thermal storage density as a basic step toward the development of new high
performance PCMs. The non-natural sugar alcohol molecules are constructed in
silico in accordance with the previously suggested molecular design guidelines:
linear elongation of a carbon backbone, separated distribution of OH groups, and
even numbers of carbon atoms. Their crystal structures are then predicted using
the random search method and first-principles calculations. Our molecular
simulation results clearly demonstrate that the non-natural sugar alcohols have
potential ability to have thermal storage density up to ~450-500 kJ/kg, which is
significantly larger than the maximum thermal storage density of the present
known organic PCMs (~350 kJ/kg). This computational study suggests that, even in
the case of H-bonded molecular crystals where the electrostatic energy
contributes mainly to thermal storage density, the molecular distortion and van
der Waals energies are also important factors to increase thermal storage
density. In addition, the comparison between the three eight-carbon non-natural
sugar alcohol isomers indicates that the selection of preferable isomers is also
essential for large thermal storage density.
PMID- 27505106
TI - Association Between Acute Infectious Mononucleosis and Vitamin D Deficiency.
AB - Epstein-Barr virus and vitamin D both have been implicated in the pathogenesis of
autoimmune diseases, especially multiple sclerosis (MS). Vitamin D influences
both innate and adaptive immune responses and has been linked to increased
susceptibility to other viral infections such as influenza. Here we aimed to
examine the association between vitamin D and acute infectious mononucleosis
(IM).This study is a case-control study that was conducted on IM patients and a
control group of healthy individuals at infectious disease clinics of Isfahan
University of Medical Sciences. Patients were recruited from January to December
2014. The viral capsid antigen (VCA) IgM titer and vitamin D levels were measured
at the time of acute infection in IM patients. We also measured vitamin D levels
in healthy controls recruited during the same period of time. A total number of
60 IM patients with the mean age of 23.26 +/- 7.59 and a healthy control group
with the mean age of 25.13 +/- 6.72 were enrolled. In the IM patients, there was
no significant association between 25(OH) D3 levels and VCA IgM titers (r =
0.190, p = 0.146). Mean 25(OH) D3 levels in IM patients were significantly lower
than in the control group (15.61 +/- 9.72 vs. 21.41 +/- 12.64, p = 0.006). Our
findings showed significantly lower vitamin D levels in IM patients at the time
of infection than in the control group, providing some evidence that the two
major risk factors for autoimmune diseases (e.g., MS) might not be independent
risk factors.
PMID- 27505108
TI - Semiquantitative Volumetry by Sequential PET/CT May Improve Prediction of
Complete Response to Neoadjuvant Chemoradiation in Patients With Distal Rectal
Cancer.
AB - BACKGROUND: Previous studies using PET/CT imaging have failed to accurately
identify complete responders to neoadjuvant chemoradiation among patients with
rectal cancer. The use of metabolic parameters alone or imprecise delineation of
baseline and residual tumor volumes may have contributed for these disappointing
findings. OBJECTIVE: The purpose of this study was to determine the accuracy of
complete response identification in rectal cancer after neoadjuvant
chemoradiation by sequential PET/CT imaging with a decrease in tumor metabolism
and volume using optimal tumor volume delineation. DESIGN: This was a
retrospective comparison of prospectively collected data from a clinical trial
(National Clinical Trial 00254683). SETTINGS: The study was conducted at a single
research center. PATIENTS: Ninety patients with cT2-4N0-2M0 distal rectal cancer
underwent sequential PET/CT at baseline and 12 weeks after neoadjuvant
chemoradiation. Quantitative metabolic analysis (median and maximal standard
uptake values), volumetric estimates (metabolic tumor volume), and composite
estimates incorporating volume and quantitative data (total lesion glycolysis)
were compared for the assessment of response to neoadjuvant chemoradiation using
receiver operating characteristic curves. Individual standard uptake value
thresholds were used according to response to neoadjuvant chemoradiation to match
metabolic activity and optimize volume delineation. MAIN OUTCOME MEASURES: The
accuracy of complete response identification by multiple volumetric and metabolic
parameters using sequential PET/CT imaging was measured. RESULTS: Variation in
total lesion glycolysis between baseline and 12-week PET/CT scans was associated
with the best area under the curve (area under the curve = 0.81 (95% CI, 0.69
0.92)) when compared with standard uptake value or metabolic tumor volume for the
identification of a complete responder. Patients with a >=92% decrease in total
lesion glycolysis between baseline and 12-week PET/CT scan had a 90% chance to
harbor complete response. LIMITATIONS: This study was limited by its lack of
interobserver agreement analysis. CONCLUSIONS: PET/CT scan using volume and
metabolic estimates with individual standard uptake value thresholds for volume
determination may provide a useful tool to predict response to neoadjuvant
chemoradiation in distal rectal cancer.
PMID- 27505109
TI - Wound Complications and Perineal Pain After Extralevator Versus Standard
Abdominoperineal Excision: A Nationwide Study.
AB - BACKGROUND: Extralevator abdominoperineal excision was introduced as an
alternative to conventional abdominoperineal excision for low rectal cancers. The
perineal dissection is more extensive with extralevator abdominoperineal excision
and leaves a greater defect. OBJECTIVE: The aim of this study was to evaluate, on
a national basis, the risk of perineal wound complications, pain, and hernia
after conventional and extralevator abdominoperineal excision performed for low
rectal cancer. DESIGN: This was a retrospective study collecting data from the
Danish Colorectal Cancer Group database and from electronic medical files of
patients. SETTINGS: The study was conducted at Danish surgical departments.
PATIENTS: A total of 445 patients operated between 2009 and 2012 with
extralevator or conventional abdominoperineal excision were included. MAIN
OUTCOME MEASURES: The main end points of this study were perineal wound
complications and pain lasting for >30 days after the operation. RESULTS: The 2
groups were demographically similar except for a higher ASA score in the
conventional group. In the extralevator group, neoadjuvant chemoradiation was
more frequent (71% vs 41%; p < 0.001), T stage was higher (more T3 tumors; 52% vs
38%; p = 0.006), and more tumors were fixed (21% vs 12%; p = 0.02). Perineal
wound complications and pain were more frequent after extralevator versus
conventional excision (44% vs 25%; p < 0.001 and 38% vs 22%; p < 0.001). After
multivariate analyses, neoadjuvant chemoradiation, extralevator excision, and
operation early in the study period were found to have a significant influence on
the risk of long-term wound complications. Neoadjuvant chemoradiation and wound
complications were significant risk factors for long-term perineal pain. Results
were similar after subgroup analyses on low tumors only. LIMITATIONS: This was a
retrospective study. The 2 groups were not completely comparable at baseline.
CONCLUSIONS: Neoadjuvant chemoradiation, extralevator compared with conventional
excision, and operation early in the study period were significant factors for
predicting perineal wound complications. Neoadjuvant chemoradiation and wound
complications were predictors of long-term perineal pain.
PMID- 27505110
TI - Prospective and Longitudinal Study of Urogenital Dysfunction After Proctectomy
for Rectal Cancer.
AB - BACKGROUND: Urogenital dysfunctions after rectal cancer treatment are well
recognized, although incidence and evolution over time are less well known.
OBJECTIVE: We aimed to assess the evolution of urogenital functions over time
after the treatment for rectal cancer. DESIGN: This is a prospective,
longitudinal cohort study. SETTINGS: This study was conducted at a quaternary
referral center for colorectal surgery. PATIENTS: A total of 250 consecutive
patients treated for rectal cancer were prospectively enrolled for urogenital
assessment. MAIN OUTCOME MEASURES: End points were the International Prostatic
Symptom Score, the International Index of Erectile Function, and the Female
Sexual Index obtained by questionnaires before (baseline status) and after
preoperative radiotherapy and 3, 6, and 12 months after surgery. RESULTS:
Overall, 169 patients (68%) responded to the questionnaires. The urinary function
decreased temporary after irradiation in men (International Prostatic Symptom
Score: 7.8 vs 4.9; p < 0.001). Sexual activity decreased significantly in women
after radiotherapy (p = 0.02), and in all patients after surgery (p < 0.001). At
12 months, sexual activity in women declined from 59% before treatment to 36% (p
= 0.02). In men, sexual activity (82% vs 57%), erectile function (71% vs 24%),
and ejaculatory function (78% vs 32%) decreased from baseline (p < 0.001). Stage
T3T4 tumors (OR = 5.72 (95% CI, 1.24-26.36)) and low rectal tumors (OR = 17.86
(95% CI, 1.58-20.00)) were independent factors of worse sexual function.
LIMITATIONS: This study was limited by the proportion of uncompleted
questionnaires, especially in women, and by its monocentric feature. CONCLUSIONS:
Most patients experienced sexual dysfunction at 12 months after surgery for
rectal cancer, and predictive factors for this dysfunction were related to
characteristics of the tumor.
PMID- 27505111
TI - Outcomes of Pelvic Exenteration with en Bloc Partial or Complete Pubic Bone
Excision for Locally Advanced Primary or Recurrent Pelvic Cancer.
AB - INTRODUCTION: Neoplasms infiltrating the pubic bone have until recently been
considered a contraindication to surgery. Paucity of existing published data in
regard to surgical techniques and outcomes exist. OBJECTIVE: This study aims to
address outcomes of our recently published technique for en bloc composite pubic
bone excision during pelvic exenteration. DESIGN: A prospective database was
reviewed to identify patients who underwent a partial or complete pubic bone
composite excision over a 12-year period. SETTINGS: This study was conducted at a
tertiary level exenteration unit. MAIN OUTCOME MEASURES: Primary outcomes
measured were resection margin and survival. Secondary outcomes included patient
and operative demographics, type of cancer, extent of pubic bone excision,
morbidity, and 30-day mortality. RESULTS: Twenty-nine of over 500 patients
undergoing exenterations (mean age, 57.9; 20 males) underwent en bloc complete
(11 patients) or partial (18 patients) composite pubic bone excision. Twenty-two
patients (76%) underwent resection for recurrent as opposed to advanced primary
malignant disease of which rectal adenocarcinoma was the most common followed by
squamous-cell carcinoma. The median operating time was 10.5 (range, 6-15) hours,
and median blood loss was 2971 (range, 300-8600) mL. Seventeen (59%) patients had
a concurrent sacrectomy performed mainly S3 and below. A total cystectomy was
performed in 26 patients (90%). Fifteen of 20 male patients (75%) had a perineal
urethrectomy. A clear (R0) resection margin was achieved in 22 patients (76%)
with a 5-year overall survival of 53% after a median follow-up of 3.2 years (r =
1.4-12.3 years). There was no 30-day mortality. Seventy percent of patients
experienced morbidity with a pelvic collection the most common. LIMITATIONS: This
study was limited because it was a retrospective review, it occurred at a single
site, and it used a small heterogeneous sample. CONCLUSION: Within the realm of
evolving exenteration surgery, en bloc composite pubic bone excision offers
results comparable to central, lateral, and posterior compartment excisions, and,
as such, is a reasonable strategy in the management of neoplasms infiltrating the
pubic bone.
PMID- 27505112
TI - Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal
Cancer in HIV-Positive Men Who Have Sex With Men.
AB - BACKGROUND: High-grade intraepithelial neoplasia is known to progress to invasive
squamous-cell carcinoma of the anus. There are limited reports on the rate of
progression from high-grade intraepithelial neoplasia to anal cancer in HIV
positive men who have sex with men. OBJECTIVES: The purpose of this study was to
describe in HIV-positive men who have sex with men with perianal high-grade
intraepithelial neoplasia the rate of progression to anal cancer and the factors
associated with that progression. DESIGN: This was a prospective cohort study.
SETTINGS: The study was conducted at an outpatient clinic at a tertiary care
center in Toronto. PATIENTS: Thirty-eight patients with perianal high-grade anal
intraepithelial neoplasia were identified among 550 HIV-positive men who have sex
with men. INTERVENTION: All of the patients had high-resolution anoscopy for
symptoms, screening, or surveillance with follow-up monitoring/treatment. MAIN
OUTCOME MEASURES: We measured the incidence of anal cancer per 100 person-years
of follow-up. RESULTS: Seven (of 38) patients (18.4%) with perianal high-grade
intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9
(95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A
diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the
lesion were associated with progression. Anal bleeding was more than twice as
common in patients who progressed to anal cancer. LIMITATIONS: There was the
potential for selection bias and patients were offered treatment, which may have
affected incidence estimates. CONCLUSIONS: HIV-positive men who have sex with men
should be monitored for perianal high-grade intraepithelial neoplasia. Those with
high-risk features for the development of anal cancer may need more aggressive
therapy.
PMID- 27505113
TI - A National Database Analysis Comparing the Nationwide Inpatient Sample and
American College of Surgeons National Surgical Quality Improvement Program in
Laparoscopic vs Open Colectomies: Inherent Variance May Impact Outcomes.
AB - BACKGROUND: Clinical and administrative databases each have fundamental
distinctions and inherent limitations that may impact results. OBJECTIVE: This
study aimed to compare the American College of Surgeons National Surgical Quality
Improvement Program and the Nationwide Inpatient Sample, focusing on the
similarities, differences, and limitations of both data sets. DESIGN: All
elective open and laparoscopic segmental colectomies from American College of
Surgeons National Surgical Quality Improvement Program (2006-2013) and Nationwide
Inpatient Sample (2006-2012) were reviewed. International Classification of
Diseases, Ninth Revision, Clinical Modification coding identified Nationwide
Inpatient Sample cases, and Current Procedural Terminology coding for American
College of Surgeons National Surgical Quality Improvement Program. Common
demographics and comorbidities were identified, and in-hospital outcomes were
evaluated. SETTINGS: A national sample was extracted from population databases.
PATIENTS: Data were derived from the Nationwide Inpatient Sample database:
188,326 cases (laparoscopic = 67,245; open = 121,081); and American College of
Surgeons National Surgical Quality Improvement Program: 110,666 cases
(laparoscopic = 54,191; open = 56,475). MAIN OUTCOME MEASURES: Colectomy data
were used as an avenue to compare differences in patient characteristics and
outcomes between these 2 data sets. RESULTS: Laparoscopic colectomy demonstrated
superior outcomes compared with open; therefore, results focused on comparing a
minimally invasive approach among the data sets. Because of sample size, many
variables were statistically different without clinical relevance. Coding
discrepancies were demonstrated in the rate of conversion from laparoscopic to
open identified in the National Surgical Quality Improvement Program (3%) and
Nationwide Inpatient Sample (15%) data sets. The prevalence of nonmorbid obesity
and anemia from National Surgical Quality Improvement Program was more than twice
that of Nationwide Inpatient Sample. Sepsis was statistically greater in National
Surgical Quality Improvement Program, with urinary tract infections and acute
kidney injury having a greater frequency in the Nationwide Inpatient Sample
cohort. Surgical site infections were higher in National Surgical Quality
Improvement Program (30-day) vs Nationwide Inpatient Sample (8.4% vs 2.6%; p <
0.01), albeit less when restricted to infections that occurred before discharge
(3.3% vs 2.6%; p < 0.01). LIMITATIONS: This is a retrospective study using
population-based data. CONCLUSION: This analysis of 2 large national databases
regarding colectomy outcomes highlights the incidence of previously unrecognized
data variability. These discrepancies can impact study results and subsequent
conclusions/recommendations. These findings underscore the importance of
carefully choosing and understanding the different population-based data sets
before designing and when interpreting outcomes research.
PMID- 27505114
TI - Clostridium difficile Infection Is Associated With Lower Inpatient Mortality When
Managed by GI Surgeons.
AB - BACKGROUND: Patients admitted with Clostridium difficile infection are managed in
a variety of settings. If their care is inadequate, these patients can rapidly
deteriorate. OBJECTIVE: The purpose of this study was to evaluate whether
mortality for patients admitted with C difficile differed between medical and
general/colorectal surgery services. DESIGN: This was a retrospective cohort
study with multivariable logistic regression used to evaluate the effect of
admitting service on in-hospital mortality rates, with propensity score matching
used to validate this relationship. SETTINGS: The study was conducted at a
single, tertiary care center. PATIENTS: Inpatients with a positive C difficile
stool test within 24 hours of admission to medical or surgical services were
identified (2005-2015) using institutional electronic data sources. MAIN OUTCOME
MEASURE: We measured inpatient mortality rate. RESULTS: Of 1175 patients, 985
(83%) were admitted to medical services, whereas 190 (17%) were admitted by
surgeons. Medical patients were older (63.9 vs 58.9 years; p = 0.001) and had a
mean of 0.6 additional comorbidities (p < 0.001); cohorts were similar regarding
vasopressors, peak white blood cell counts, and rate of intensive care unit
admissions. Mortality was lower among surgery patients (2.6% vs 6.8%; p = 0.028),
and logistic regression demonstrated lower odds of mortality for this group OR =
0.18 (95% CI, 0.05-0.58)). After propensity score matching for age,
comorbidities, and severity of disease, this difference was confirmed (2.6% vs.
9.5%). A higher incidence of total colectomy for surgery patients (14.2% vs 0.4%)
was a causal factor in their longer lengths of stay and higher total hospital
costs. The time between orders for stool testing and metronidazole therapy was
shorter in the surgery group (1.8 vs 3.8 hours; p = 0.002), although this trend
was not observed with vancomycin therapy. LIMITATIONS: This was a retrospective
study from a single institution, thereby limiting generalizability, with a lack
of information regarding premorbid creatinine levels, ileus, or megacolon.
CONCLUSIONS: In-hospital mortality rates for patients admitted with C difficile
were lower on surgery services, perhaps in part related to higher colectomy
rates.
PMID- 27505115
TI - Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic
Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital.
AB - BACKGROUND: Prior industry conducted studies have shown that long acting
liposomal bupivacaine injection improves pain control postoperatively. OBJECTIVE:
To evaluate whether liposomal bupivacaine reduced the use of postoperative opioid
(http://links.lww.com/DCR/A253) pain medication as compared to standard
bupivacaine following colorectal surgery. DESIGN: A double blinded, prospective,
randomized controlled trial comparing liposomal bupivacaine versus standard
bupivacaine in patients undergoing elective colon resection. SETTINGS: Community
hospital with general surgery residency program with all cases performed by
colorectal surgeons. PATIENTS: Fifty-seven patients were randomized and reported
as intention-to-treat analysis with 6 protocol violations. Sensitivity analysis
excluding these 6 patients demonstrated no change in study results or conclusion.
Mean age was 67 +/- 2 years and 56% were male. There were 36 patients who
underwent minimally invasive surgery, and 21 patients had an open colon
resection. INTERVENTIONS: Experimental arm received liposomal bupivacaine while
control arm received standard bupivacaine. MAIN OUTCOME MEASURES: Primary outcome
measure was intravenous hydromorphone equivalent used via PCA during first 48
hours after operation. RESULTS: There was no significant difference between the
two groups in the amount of opioid used orally or intravenously in the
postoperative period. The primary outcome measure was PCA hydromorphone
consumption during first two postoperative days after operation (hydromorphone
equivalent use in standard bupivacaine group 11.3 +/- 8.9 mg versus 13.3 +/- 11.9
mg in liposomal bupivacaine group, p = 0.58 Mann-Whitney test). LIMITATIONS:
Small pragmatic trials typically remain underpowered for secondary analyses. A
larger study could help to further delineate other outcomes that are impacted by
postoperative pain. CONCLUSIONS: Liposomal bupivacaine did not change the amount
of opioid used postoperatively. Based on our study, liposomal bupivacaine does
not provide any added benefit over conventional bupivacaine after colon
resection. (ClinicalTrials.gov: NCT02052557).
PMID- 27505116
TI - Seasonal Variation in Diverticulitis: Evidence From Both Hemispheres.
AB - BACKGROUND: Diverticulitis is a common and morbid disease with incompletely
understood risk factors and pathophysiology. Geographic and, recently, seasonal
trends in diverticulitis have been described in the United States. OBJECTIVE: The
purpose of this study was to investigate and compare seasonal trends in urgent
hospital admission for diverticulitis in geographically distinct populations in
the northern and southern hemispheres. DESIGN: Inpatient, urgent admissions for
diverticulitis were identified within the Dr Foster Intelligence Global
Comparators Dataset, a global benchmarking collaborative. SETTINGS: Admissions to
participating hospitals in the United Kingdom, Australia, and the United States
were identified between 2008 and 2013. PATIENTS: A total of 18,672 urgent
admissions for diverticulitis were identified among 5.5-million admissions. MAIN
OUTCOME MEASURES: Four separate hypothesis testing methods were used to identify
seasonal trends in diverticulitis admissions among international patient
populations. RESULTS: Seasonal trends were present in all 3 countries. A summer
peak was observed in both hemispheres using multiple statistical testing methods.
Logistic regression analyses identified summer months as significantly associated
with diverticulitis admission in all 3 countries. LIMITATIONS: This study is
limited by restriction to inpatient admissions, reliance on administrative data,
and participation of select hospitals within the database. CONCLUSIONS: These
data suggest a shared seasonal risk factor among geographically distinct
populations for diverticulitis.
PMID- 27505117
TI - Sacral Nerve Stimulation Fails to Offer Long-term Benefit in Patients With Slow
Transit Constipation.
AB - BACKGROUND: Sacral nerve stimulation is proposed as a treatment for slow-transit
constipation. However, in our randomized controlled trial we found no therapeutic
benefit over sham stimulation. These patients have now been followed-up over a
long-term period. OBJECTIVE: The purpose of this study was to assess the long
term efficacy of sacral nerve stimulation in patients with scintigraphically
confirmed slow-transit constipation. DESIGN: This study was designed for long
term follow-up of patients after completion of a randomized controlled trial.
SETTINGS: It was conducted at an academic tertiary public hospital in Sydney.
PATIENTS: Adults with slow-transit constipation were included. MAIN OUTCOME
MEASURES: At the 1- and 2-year postrandomized controlled trial, the primary
treatment outcome measure was the proportion of patients who reported a feeling
of complete evacuation on >2 days per week for >=2 of 3 weeks during stool diary
assessment. Secondary outcome was demonstration of improved colonic transit at 1
year. RESULTS: Fifty-three patients entered long-term follow-up, and 1 patient
died. Patient dissatisfaction or serious adverse events resulted in 44 patients
withdrawing from the study because of treatment failure by the end of the second
year. At 1 and 2 years, 10 (OR = 18.8% (95% CI, 8.3% to 29.3%)) and 3 patients
(OR = 5.7% (95% CI, -0.5% to 11.9%)) met the primary outcome measure. Colonic
isotope retention at 72 hours did not differ between baseline (OR = 75.6% (95%
CI, 65.7%-85.6%)) and 1-year follow-up (OR = 61.7% (95% CI, 47.8%-75.6%)).
LIMITATIONS: This study only assessed patients with slow-transit constipation.
CONCLUSIONS: In these patients with slow-transit constipation, sacral nerve
stimulation was not an effective treatment.
PMID- 27505118
TI - Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A
Systematic Review and Meta-Analysis.
AB - BACKGROUND: Chronic anal fissures are associated with significant morbidity and
reduced quality of life. Studies have investigated the efficacy of botulinum
toxin with variable results; thus, there is currently no consensus on botulinum
toxin dose or injection sites. OBJECTIVE: This study aimed to systematically
analyze trials studying the efficacy of botulinum toxin for treatment of chronic
anal fissure to identify an optimum dosage and injection regimen. DATA SOURCES: A
comprehensive review of the literature was conducted according to PRISMA
guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were
searched from inception to June 2015. STUDY SELECTION: All clinical trials that
investigated the efficacy of botulinum toxin for chronic anal fissure were
selected according to specific criteria. INTERVENSIONS: The interventions used
were various doses of botulinum toxin. OUTCOME MEASURES: Clinical outcomes,
dosage, and injection site data were evaluated with weighted pooled results for
each dosage and 95% confidence intervals. RESULTS: There were 1158 patients, with
661 in botulinum toxin treatment arms, from 18 clinical trials included in this
review. The outcomes of interest were 3-month healing, incontinence, and
recurrence rates. Meta-regression analysis demonstrated a small decrease in
healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a
small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048)
with each increase in dosage and a small increase in recurrence rate (1.037
times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum
injection site could not be determined. LIMITATIONS: This study was limited by
weaknesses in the underlying evidence, such as variable quality, short follow-up,
and a limited range of doses represented. CONCLUSIONS: Fissure healing with lower
doses of botulinum toxin is as effective as with high doses. Lower doses also
reduce the risk of incontinence and recurrence in the long term.
PMID- 27505119
TI - Should We Give Up The Search for a Clinically Useful Gene Signature for the
Prediction of Response of Rectal Cancer to Neoadjuvant Chemoradiation?
PMID- 27505120
TI - Lessons Learned From the Quest for Gene Signatures That Predict Treatment
Response in Rectal Cancer.
PMID- 27505121
TI - How to Size the Anal Canal Circumference When Implanting a Magnetic Anal
Sphincter for Fecal Incontinence. Evolution and Update of a New Surgical
Technique.
AB - INTRODUCTION: Magnetic anal sphincter augmentation improves function and quality
of life of patients with severe fecal incontinence substantially. Measuring the
anal circumference exactly with a sizing tool represents a crucial step of the
procedure because it determines the correct size and success of the definite
implant. OBJECTIVE: This study aims to illustrate the consequent development of 3
different sizing models and the use of the recent sizing tool. TECHNIQUE: After
dissection of a tunnel around the anal canal through a ventral perineal incision,
the sizing tool is inserted by using a specially designed introducer to measure
the circumference for the appropriate size of implant. First- and second
generation sizing tools could only approximate the final implant size and impeded
standardization. The latest sizing model resembles the actual implant with
magnetic beads, it is nonstretchable, and it is closable end-to-end. RESULTS: The
development of 3 measuring tools has progressively improved the accuracy of
estimating the correct size of the definitive implant, and the application of the
latest sizer seems easy, comfortable in use, and accurate as experienced in our
first cases. CONCLUSION: The latest device contributes to standardization of the
procedure and therefore facilitates the learning curve for newcomers of the
method and could avoid the need for radiological on-table control in the near
future.
PMID- 27505124
TI - Helping the Helpers: Assisting Staff and Volunteer Workers Before, During, and
After Disaster Relief Operations.
AB - Self-care strategies and system supports employed in preparation for, during, and
after disaster relief operations (DROs) are crucial to relief worker well-being
and the overall effectiveness of relief efforts. Relief organizations and
management must structure DROs in a manner that promotes self-care and workers
must implement proper self-care strategies. Proper self-care before, during, and
after a DRO can reduce negative reactions to stressful emergency work and promote
growth, mastery, and self-efficacy after the experience. Therefore, the purpose
of this article is to discuss the importance of organizational supports and self
care strategies in disaster relief settings. This article emphasizes the role of
both individual and management participation and commitment to relief worker
support and positive experience in DROs and provides suggestions for doing so.
These suggestions are derived from the empirical and experiential literature and
extensions from the theoretical background, and from our experience as managers
in DROs.
PMID- 27505126
TI - Isolation and Structure of Germylene-Germyliumylidenes Stabilized by N
Heterocyclic Imines.
AB - The ditopic germanium complex FGe(NIPr)2 Ge[BF4 ] (3[BF4 ]; IPr=1,3-bis(2,6
diisopropylphenyl)imidazolin-2-ylidene) is prepared by the reaction of the
amino(imino)germylene (Me3 Si)2 NGeNIPr (1) with BF3 ?OEt2 . This monocation is
converted into the germylene-germyliumylidene 3[BAr(F) 4 ] [Ar(F) =3,5-(CF3 )2
C6 H3 ] by treatment with Na[BAr(F) 4 ]. The tetrafluoroborate salt 3[BF4 ]
reacts with 2 equivalents of Me3 SiOTf to give the novel complex (OTf)(GeNIPr)2
[OTf] (4[OTf]), which affords 4[BAr(F) 4 ] and 4[Al(OR(F) )4 ] [R(F) =C(CF3 )3 ]
after anion exchange with Na[BAr(F) 4 ] or Ag[Al(OR(F) )4 ], respectively. The
computational, as well as crystallographic study, reveals that 4(+) has
significant bis(germyliumylidene) dication character.
PMID- 27505125
TI - Decreased Soluble Guanylate Cyclase Contributes to Cardiac Dysfunction Induced by
Chronic Doxorubicin Treatment in Mice.
AB - AIMS: The use of doxorubicin, a potent chemotherapeutic agent, is limited by
cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase
(sGC) enzyme activity contributes to the development of doxorubicin-induced
cardiotoxicity. RESULTS: Doxorubicin administration (20 mg/kg, intraperitoneally
[IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether
decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we
studied mice with cardiomyocyte-specific deficiency of the sGC alpha1-subunit
(mice with cardiomyocyte-specific deletion of exon 6 of the sGCalpha1 allele
[sGCalpha1-/-CM]). After 12 weeks of doxorubicin administration (2 mg/kg/week
IP), left ventricular (LV) systolic dysfunction was greater in sGCalpha1-/-CM
than WT mice. To further assess whether reduced sGC activity plays a pathogenic
role in doxorubicin-induced cardiotoxicity, we studied a mouse model in which
decreased cardiac sGC activity was induced by cardiomyocyte-specific expression
of a dominant negative sGCalpha1 mutant (DNsGCalpha1) upon doxycycline removal
(Tet-off). After 8 weeks of doxorubicin administration, DNsGCalpha1tg/+, but not
WT, mice displayed LV systolic dysfunction and dilatation. The difference in
cardiac function and remodeling between DNsGCalpha1tg/+ and WT mice was even more
pronounced after 12 weeks of treatment. Further impairment of cardiac function
was attenuated when DNsGCalpha1 gene expression was inhibited (beginning at 8
weeks of doxorubicin treatment) by administering doxycycline. Furthermore,
doxorubicin-associated reactive oxygen species generation was higher in sGCalpha1
deficient than WT hearts. Innovation and Conclusion: These data demonstrate that
a reduction in cardiac sGC activity worsens doxorubicin-induced cardiotoxicity in
mice and identify sGC as a potential therapeutic target. Various pharmacological
sGC agonists are in clinical development or use and may represent a promising
approach to limit doxorubicin-associated cardiotoxicity. Antioxid. Redox Signal.
26, 153-164.
PMID- 27505127
TI - Development and validation of UHPLC-MS/MS methods for the quantification of
colistin in plasma and dried plasma spots.
AB - Quantification of colistin in plasma samples may be very useful in optimizing
therapy especially in special patients' population. Nevertheless, therapeutic
drug monitoring of colistin is still limited probably for the low number of
laboratories which perform this analysis and for high shipment costs. We
developed and validated new UHPLC-MS/MS methods to quantify colistin in plasma
and in dried plasma spots (DPS) collected on dried sample spots devices (DSSD).
Colistin A, Colistin B and polimixin B, used as internal standard, were detected
using multiple reaction monitoring (MRM) of the following specific transitions:
585.5->534.9; 576, 578.5->527.9; 568.9 and 602.5->100.9, 551.9, 592.8,
respectively. Colistin A and B were extracted from plasma using protein
precipitation and from DSSD using an extraction basic solution. Both methods were
validated, and the mean intra and inter-day accuracies and precisions were in
accordance with FDA and EMA guidelines. Colistin in DPS was found to be stable
for at least one week at room temperature (20-25 degrees C). A statistically
significant linear correlation was found between colistin extracted from plasma
and from DPS [r(2) 0.9864 (P<0.0001, 95% CI 0.9699-0.9939) for colistin A and
0.9695 (P<0.0001, 95% CI 0.9310-0.9866) for colistin B, respectively]. DPS on
DSSD represents a safe and cheap strategy to store and ship at room temperature
plasma samples. Thus, it is suited for pharmacokinetic studies and therapeutic
drug monitoring of colistin.
PMID- 27505129
TI - "In Times Like These".
PMID- 27505128
TI - Development of a simple, rapid, and robust liquid chromatographic method for the
simultaneous determination of sulfalene, sulfadoxine, and pyrimethamine in
tablets.
AB - A simple, cost effective, accurate, and precise RP-HPLC method was developed for
the simultaneous determination of sulfalene and sulfadoxine in fixed dose dual
combinations with pyrimethamine together with their related substances.
Proprietary products containing these combinations are often being prescribed in
malaria endemic countries. Quantification of the active compounds and impurity
profiling was achieved using two standard C18 columns with a mobile phase being
composed of 60% (v/v) of a 0.05M KH2PO4 buffer solution (pH=2.6) and 40% (v/v) of
methanol, applying an isocratic elution mode and a detection wavelength of 215nm.
The method allows a quick quantitative determination of sulfadoxine and sulfalene
and the separation of the respective impurities within a total runtime of
approximately 15min and was validated with respect to specificity, linearity,
precision, accuracy, limits of detection and quantification, robustness, and
stability of the standard and sample solutions. The method is simpler than the
corresponding method described in the International Pharmacopoeia and the United
States Pharmacopoeia in terms of being easy to apply, being less time consuming,
and utilizing reagents and chemicals which are cost efficient.
PMID- 27505130
TI - Use of Surface Photovoltage Spectroscopy to Measure Built-in Voltage, Space
Charge Layer Width, and Effective Band Gap in CdSe Quantum Dot Films.
AB - Surface photovoltage spectroscopy (SPS) was used to study the photochemistry of
mercaptoethanol-ligated CdSe quantum dot (2.0-4.2 nm diameter) films on indium
doped tin oxide (ITO) in the absence of an external bias or electrolyte. The n
type films generate negative voltages under super band gap illumination (0.1-0.5
mW cm(-2)) by majority carrier injection into the ITO substrate. The photovoltage
onset energies track the optical band gaps of the samples and are assigned as
effective band gaps of the films. The photovoltage values (-125 to -750 mV) vary
with quantum dot sizes and are modulated by the built-in potential of the CdSe
ITO Schottky type contacts. Deviations from the ideal Schottky model are
attributed to Fermi level pinning in states approximately 1.1 V negative of the
ITO conduction band edge. Positive photovoltage signals of +80 to +125 mV in
films of >4.0 nm nanocrystals and in thin (70 nm) nanocrystal films are
attributed to electron-hole (polaron) pairs that are polarized by a space charge
layer at the CdSe-ITO boundary. The space charge layer is 70-150 nm wide, based
on thickness-dependent photovoltage measurements. The ability of SPS to directly
measure built-in voltages, space charge layer thickness, sub-band gap states, and
effective band gaps in drop-cast quantum dot films aids the understanding of
photochemical charge transport in quantum dot solar cells.
PMID- 27505131
TI - Palladium-Catalyzed Enantioselective Three-Component Synthesis of alpha
Arylglycines.
AB - A general Pd-catalyzed, enantioselective three-component synthesis of alpha
arylglycines starting from sulfonamides, glyoxylic acid derivatives, and boronic
acids was developed. This operationally straightforward procedure enables the
preparation of a wide variety of alpha-arylglycines in high yields and excellent
levels of enantioselectivity from a simple set of readily available starting
materials. Incorporation of Pbf-amides gives a racemization-free access to N
unprotected alpha-arylglycines.
PMID- 27505132
TI - Successful surgery in lesional epilepsy secondary to posterior quandrant ulegyria
coexisting with benign childhood focal epilepsy: A case report.
AB - The present study reports, for the first time, a rare case of benign childhood
focal epilepsy(BCFE) coexisting with lesional epilepsy secondary to
parietooccipital ulegyria. The patient underwent right parietooccipital lobe
disconnection plus tailored resection of temporooccipitoparietal junction cortex
under electrocorticography (ECoG) monitoring. Post-operatively, there was no
impairment of neurological function and the patient only experiences a few
breakthrough benign partial seizures during sleep.
PMID- 27505133
TI - Prognosis of meningiomas in the early 1970s and today.
AB - OBJECTIVE: The benefit of the current strategy of diagnosis and treatment of
meningiomas in contrast to the standard treatment in use before computer
tomographic and magnetic resonance imaging and before the microsurgical era has
not yet been determined. METHODS: Two groups of patients were compared, those on
which surgery was performed before the year of 1985, when computer tomographic
(CT) imaging was not yet available in our clinic and those who were treated after
at the Neurosurgical Department of Saarland University. Average follow-up time
was 17.9+/-9.3years for group 1 and 9.2+/-4.3years for group 2. RESULTS: The
number of patients with advanced age who had surgical treatment was significantly
increased in the second group, whereas the number of perioperative complications
found was nearly equal in both groups (17.8% vs. 18.8%). Nevertheless,
perioperative morbidity was reduced from 2.2% to 1.2%. The postoperative
recurrence free time period could be revealed to be longer in the first
collective (p<0.0001). Furthermore, this study shows a notable increase of the
incidence of WHO grade II meningiomas in patients treated after 1985.
CONCLUSIONS: Based on the presented results, the overall prognosis for patients
with meningiomas has changed from the 1960s until today, since over the last two
decades there has been a prolonged progression free survival time in addition to
a reduced perioperative mortality rate. In the postoperative management of these
patients genetic aberrations and microbiological markers should be considered as
prognostic factors for meningiomas in addition to histopathological grading.
PMID- 27505134
TI - L1CAM expression in endometrial carcinomas: an ENITEC collaboration study.
AB - BACKGROUND: Identification of aggressive endometrioid endometrial carcinomas
(EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome.
L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in
stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and
NEECs. This study analyses L1CAM expression in a clinically representative cohort
of endometrial carcinomas. METHODS: The expression of L1CAM was
immunohistochemically determined in 1199 endometrial carcinomas, treated at one
of the European Network for Individualized Treatment of Endometrial Cancer
(ENITEC) centres. Staining was considered positive when >10% of the tumour cells
expressed L1CAM. The association between L1CAM expression and several
clincopathological characteristics and disease outcome was calculated. RESULTS:
In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160
advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was
associated with advanced stage, nodal involvement, high tumour grade, non
endometrioid histology, lymphovascular space invasion, and distant recurrences in
all cases, and with reduced survival in the EECs, but not in the NEECs.
CONCLUSIONS: The expression of L1CAM is a strong predictor of poor outcome in
EECs, but not NEECs. It is strongly associated with non-endometrioid histology
and distant spread, and could improve the postoperative selection of high-risk
endometrial carcinomas. The value of L1CAM expression in the preoperative
selection of high-risk endometrial carcinomas should be studied.
PMID- 27505135
TI - Excessive blood pressure increase with exercise and risk of all-cause mortality
and cardiac events.
AB - BACKGROUND: The association of an excessive blood pressure increase with exercise
(EBPIE) on cardiovascular outcomes remains controversial. We sought to assess its
impact on the risk of all-cause mortality and major cardiac events in patients
with known or suspected coronary artery disease (CAD) referred for stress
testing. MATERIALS AND METHODS: Exercise echocardiography was performed in 10 047
patients with known or suspected CAD. An EBPIE was defined as an increase in
systolic blood pressure with exercise >= 80 mmHg. The endpoints were all-cause
mortality and major cardiac events (MACE), including cardiac death or nonfatal
myocardial infarction (MI). RESULTS: Overall, 573 patients exhibited an EBPIE
during the tests. Over a mean follow-up of 4.8 years, there were 1950 deaths
(including 725 cardiac deaths), 1477 MI and 1900 MACE. The cumulative 10-year
rates of all-cause mortality, cardiac death, nonfatal MI and MACE were 32.9%,
13.1%, 26.9% and 33% in patients who did not develop an EBPIE vs. 18.9%, 4.7%,
17.5% and 20.7% in those experiencing an EBPIE, respectively (P < 0.001 for all
comparisons). In Cox regression analyses, an EBPIE remained predictive of all
cause mortality (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.59-0.91,
P = 0.004), cardiac death (HR 0.67, 95% CI 0.46-0.98, P = 0.04), MI (HR 0.67, 95%
CI 0.52-0.86, P = 0.002) and MACE (HR 0.69, 95% CI 0.56-0.86, P = 0.001).
CONCLUSIONS: An EBPIE was associated with a significantly lower risk of mortality
and MACE in patients with known or suspected CAD referred for stress testing.
PMID- 27505136
TI - Chemoenzymatic Total Synthesis of (+)-Galanthamine and (+)-Narwedine from
Phenethyl Acetate.
AB - The stereoselective total synthesis of unnatural (+)-galanthamine starting from
phenethyl acetate is described. Chirality was introduced via microbial
dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A)
to the corresponding cis-cyclohexadi-enediol, configuration of which provided the
absolute stereochemistry of the ring C of (+)-galanthamine. Intramolecular Heck
cyclization was used to form the quaternary carbon and dibenzofuran
functionality. The synthesis of (+)-galanthamine was completed in a total of ten
steps and an overall yield of 5.5 %. Experimental and spectral data are provided
for all new compounds.
PMID- 27505137
TI - A novel system for embryo-larval toxicity testing of pelagic fish: Applications
for impact assessment of Deepwater Horizon crude oil.
AB - Key differences in the developmental process of pelagic fish embryos, in
comparison to embryos of standard test fish species, present challenges to
obtaining sufficient control survival needed to successfully perform traditional
toxicity testing bioassays. Many of these challenges relate to the change in
buoyancy, from positive to negative, of pelagic fish embryos that occurs just
prior to hatch. A novel exposure system, the pelagic embryo-larval exposure
chamber (PELEC), has been developed to conduct successful bioassays on the early
life stages (ELSs; embryos/larvae) of pelagic fish. Using this unique
recirculating upwelling system, it was possible to significantly improve control
survival in pelagic fish ELS bioassays compared to commonly used static exposure
methods. Results demonstrate that control performance of mahi-mahi (Coryphaena
hippurus) embryos in the PELEC system, measured as percent survival after 96-hrs,
significantly outperformed agitated static exposure and static exposure systems.
Similar significant improvements in 72-hr control survival were obtained with
yellowfin tuna (Thunnus albacares). The PELEC system was subsequently used to
test the effects of photo-induced toxicity of crude oil to mahi-mahi ELSs over
the course of 96-hrs. Results indicate a greater than 9-fold increase in toxicity
of Deepwater Horizon (DWH) crude oil during co-exposure to ambient sunlight
compared to filtered ambient sunlight, revealing the importance of including
natural sunlight in 96-hr DWH crude oil bioassays as well as the PELEC system's
potential application in ecotoxicological assessments.
PMID- 27505138
TI - Nanocomposite of exfoliated bentonite/g-C3N4/Ag3PO4 for enhanced visible-light
photocatalytic decomposition of Rhodamine B.
AB - Novel visible-light-driven heterojunction photocatalyst comprising exfoliated
bentonite, g-C3N4 and Ag3PO4 (EB/g-C3N4/Ag3PO4) was synthesized by a facile and
green method. The composites EB/g-C3N4/Ag3PO4 were characterized by X-ray
diffraction, Transmission electron microscopy, Fourier transform infrared
spectroscopy, UV-Vis diffuse reflectance spectroscopy and the Brunauer, Emmett,
and Teller (BET) surface area method. Under visible light irradiation, EB/g
C3N4/Ag3PO4 composites displayed much higher photocatalytic activity than that of
either pure g-C3N4 or pure Ag3PO4 in the degradation of Rhodamine B (RhB). Among
the hybrid photocatalysts, EB/g-C3N4/Ag3PO4 composite containing 20 wt% Ag3PO4
exhibited the highest photocatalytic activity for the decolorization of RhB.
Under the visible-light irradiation, the RhB dye was completely decolorized in
less than 60 min. The enhanced photocatalytic performance is attributed to the
stable structure, enlarged surface area, strong adsorbability, strong light
absorption ability, and high-efficiency separation rate of photoinduced electron
hole pairs. Our finding paves a way to design highly efficient and stable visible
light-induced photocatalysts for practical applications in wastewater treatment.
PMID- 27505140
TI - A case of pulmonary artery sling where onset Was induced by therapeutic
hypothermia.
AB - A neonate with severe neonatal asphyxia was treated with therapeutic hypothermia.
He developed hypothermia-induced respiratory deterioration, after which
congenital tracheal stenosis and pulmonary artery sling were diagnosed. Even low
grade hypothermia is likely to induce bronchial narrowing in neonates, especially
in neonates with congenital respiratory tract anomalies. Congenital tracheal
stenosis represents a potential pitfall in differential diagnosis and should be
carefully ruled out in cases of bronchial narrowing episode induced by
therapeutic hypothermia. Pediatr Pulmonol. 2017;52:E7-E10. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27505139
TI - miR-17-3p Exacerbates Oxidative Damage in Human Retinal Pigment Epithelial Cells.
AB - Oxidative stress has been shown to contribute to the development of age-related
macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules
that function in RNA silencing and post-transcriptional regulation of gene
expression. We showed miR-17-3p to be elevated in macular RPE cells from AMD
patients and in ARPE-19 cells under oxidative stress. Transfection of miR-17-3p
mimic in ARPE-19 induced cell death and exacerbated oxidative lethality that was
alleviated by miR-17-3p inhibitor. The expression of antioxidant enzymes
manganese superoxide dismutase (MnSOD) and thioredoxin reductase-2 (TrxR2) were
suppressed by miR-17-3p mimic and reversed by miR-17-3p inhibitor. These results
suggest miR-17-3p aggravates oxidative damage-induced cell death in human RPE
cells, while miR-17-3p inhibitor acts as a potential protector against oxidative
stress by regulating the expression of antioxidant enzymes.
PMID- 27505141
TI - Quercetin Influence on Thermal Denaturation of Bovine Serum Albumin.
AB - The effect of quercetin (QUER) binding on bovine serum albumin (BSA) thermal
denaturation was systematically investigated by means of differential scanning
calorimetry (DSC). Additional information concerning thermodynamic and structural
binding parameters was provided by isothermal titration calorimetry (ITC) and
molecular docking. The most relevant effect of QUER is manifested in the
modification of the two-step thermal fingerprint of protein denaturation. Higher
QUER concentrations result in a single-step denaturation thermogram, ascribed to
the interplay between specific and nonspecific binding and enhancement of the
solvent unfolding action. Analysis of ITC data indicate sequential binding of two
molecules of QUER occurring spontaneously at different binding sites of BSA
involving hydrophobic, electrostatic and hydrogen binding forces. Identification
of QUER binding sites was possible through corroboration of DSC runs in the
presence of site markers and molecular docking. Modeling of ligand-protein
interaction confirmed the experimental data. On one hand, a neutral form of QUER
binds in a nonplanar conformation to Sudlow's site I, a large hydrophobic cavity
of subdomain IIA of BSA and decreases its thermal stability. On the other hand, a
second molecule of QUER, the anionic form, is bound in planar conformation to
Sudlow's site II, situated in the subdomain IIIA of the folded protein, and
increases the thermal stability of the corresponding structural domain of the
protein.
PMID- 27505142
TI - Utilization and efficacy of computational gait analysis for hamstring lengthening
surgery.
AB - A retrospective analysis of computational gait studies performed in a single lab
over a 12 year period was undertaken to characterize how recommendations to
perform or not to perform hamstring lengthenings were utilized by physicians and
the effect on outcomes. 131 Subjects were identified as either having hamstring
lengthening considered by the referring surgeon, recommended by gait analysis
data, or performed. A subset of this data meeting inclusion criteria for pre- and
post-surgical timeframes, and bilateral diagnosis was further analyzed to assess
the efficacy of the recommendations. There was initial agreement between planned
procedures and recommended procedures in just 41% of the cases. Including the
cases where there was agreement, gait analysis altered the initial procedure in
54%. In the cases where the initial plan was not supported by gait data, surgeons
followed gait recommendations in 77%. In subjects who underwent hamstring
lengthening, when surgeons followed or agreed with gait recommendations, patients
were 3.6 times more likely to experience a positive outcome.
PMID- 27505143
TI - Reference data for performances on the standardized walking obstacle course in
children developing typically.
AB - PURPOSE: To establish reference performance groups on the Standardized Walking
Obstacle Course (SWOC) a pathway to screen ambulation for children developing
typically. METHODS: SWOC tests ambulation under three conditions: walk (W), walk
with tray (WT) and walk wearing sunglasses (WG). One trial consisted of standing
up, walking the course in one direction and sitting down. Children (n=355)
completed two trials per condition. Trial measures included time to complete
(seconds) and numbers of steps, stumbles, and steps off path. RESULTS: Trial 1
and trial 2 for time and number of steps are significantly different (p=0.0005),
but highly correlated (r=0.93 and r=0.96) therefore their average was used to
establish reference data. Gender was not a significant factor. Age and height
predict performances in all conditions, but measures between age groups were not
always significantly different. Significant different measures by height groups
could be established across all conditions, therefore reference data was
established using three height groups. CONCLUSION: Reference values will assist
clinicians to compare a child's performance on the SWOC based on an individual
height because this can vary within and between ages thus screening for possible
ambulation limitations.
PMID- 27505144
TI - Postural sway in children: A literature review.
AB - BACKGROUND AND AIM: Static posturography can serve as an easy and fast way to
determine whether a child possesses sufficient balance control in different
sensory conditions. Therefore, the aim of this review is to map age-related
differences in postural sway during childhood in typically developing children,
using static posturography and to provide an overview of the available (age
specific) reference values in scientific literature. METHODS: The search strategy
was performed in five databases (Pubmed, Web of Science, ScienceDirect, Cochrane
Clinical Trials, Medline (Ovid)) November 2nd 2014 and updated twice: March 16th
2015 and July 20th 2015. The following keywords were used: (children OR child)
AND ("postural control" OR "postural stability" OR equilibrium OR posture OR
"postural balance"[mesh]) AND ("quiet stance" OR standing OR stance OR "quiet
stance" OR static) AND ("postural sway" OR posturography OR "body sway" OR
stabilography OR "trunk sway" OR "medio-lateral sway" OR "antero-posterior
sway"). Relevant studies were identified using predefined selection criteria,
applied on title and abstract (phase 1) and on full text (phase 2), supplemented
with reference screening after the second phase. RESULTS: A total of 14 studies
met the criteria. This review showed three main findings: 1) during natural
bipedal stance with the eyes open, all studies reported a decrease in postural
sway with increasing age, with conflicting results on the (non-)linearity of its
development, 2) with eyes closed, all children show more sway than with eyes open
and 3) only four studies reported numeric sway values that could serve as
reference values, mainly focusing on children aged five and older. CONCLUSION:
Considerable disagreement exists on the (non-)linearity of the development of
postural sway in children. By choosing arbitrary age categories, it remains
unclear between which age groups differences are situated. Future research is
necessary to determine for which age groups age-specific reference values are
relevant.
PMID- 27505145
TI - Serum HBV core-related antigen is a good predictor for spontaneous HBeAg
seroconversion in chronic hepatitis B patients.
AB - Early prediction of spontaneous hepatitis B virus e antigen (HBeAg)
seroconversion is pivotal in the prevention of unnecessary drug prescription,
corresponding financial burden, and adverse reactions. One hundred and thirteen
chronic hepatitis B patients with HBeAg-positive in the immune active phase were
followed up for about 1.5 years. Patients were classified into two groups:
spontaneous HBeAg seroconversion group (group A, n = 18) and non-spontaneous
HBeAg seroconversion group. Among the non-spontaneous HBeAg seroconversion group,
35 patients were selected as controls (group B, n = 35). At week 12, there was a
significant difference in hepatitis B core-related antigen (HBcrAg) levels
between the two groups (group A 4.32 +/- 1.05 log10 kU/ml, and group B 5.16 +/-
0.53 log10 kU/ml, P = 0.004), and this significance magnified at week 28. Only
two variables, HBcrAg level and the reduction in the HBcrAg levels (DeltaHBcrAg)
at week 28 were enrolled, with the odds ratio of 4.19 and 0.21, respectively. The
optimal cutoffs of HBcrAg levels and the DeltaHBcrAg at week 28 were 4.90 and
2.00 log10 kU/ml, respectively. The positive predictive value and negative
predictive value of HBcrAg levels at week 28 were 73.9% and 96.7%, respectively.
The positive predictive value and negative predictive value of the DeltaHBcrAg at
week 28 were 76.2% and 93.8%, respectively. The measurement of HBcrAg is useful
for monitoring the natural course of chronic hepatitis B virus infection. The
dynamics of HBcrAg levels could accurately predict the spontaneous HBeAg
seroconversion. J. Med. Virol. 89:463-468, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27505146
TI - La2SrCr2O7: Controlling the Tilting Distortions of n = 2 Ruddlesden-Popper Phases
through A-Site Cation Order.
AB - Structural characterization by neutron diffraction, supported by magnetic, SHG,
and MU(+)SR data, reveals that the n = 2 Ruddlesden-Popper phase La2SrCr2O7
adopts a highly unusual structural configuration in which the cooperative
rotations of the CrO6 octahedra are out of phase in all three Cartesian
directions (PhiPhiPhiz/PhiPhiPhiz; a(-)a(-)c(-)/a(-)a(-)c(-)) as described in
space group A2/a. First-principles DFT calculations indicate that this unusual
structural arrangement can be attributed to coupling between the La/Sr A-site
distribution and the rotations of the CrO6 units, which combine to relieve the
local deformations of the chromium-oxygen octahedra. This coupling suggests new
chemical "handles" by which the rotational distortions or A-site cation order of
Ruddlesden-Popper phases can be directed to optimize physical behavior. Low
temperature neutron diffraction data and MU(+)SR data indicate La2SrCr2O7 adopts
a G-type antiferromagnetically ordered state below TN ~ 260 K.
PMID- 27505147
TI - Tumor Necrosis Factor Alpha Promotes Osteoclast Formation Via PI3K/Akt Pathway
Mediated Blimp1 Expression Upregulation.
AB - Tumor necrosis factor alpha (TNF-alpha)-induced osteoclastogenesis have profound
effects in states of inflammatory osteolysis such as rheumatoid arthritis,
periprosthetic implant loosening, and periodontitis. However, the exact
mechanisms by which TNF-alpha promotes RANKL-induced osteoclast formation remains
poorly understood. B lymphocyte-induced maturation protein-1 (Blimp1) is a
transcriptional repressor that plays crucial roles in the differentiation and/or
function of various kinds of cells including osteoclasts. A novel mechanism was
identified where TNF-alpha-mediated Blimp1 expression, which contributed to RANKL
induced osteoclastogenesis. It is shown that TNF-alpha could promote the level of
Blimp1 expression during osteoclast differentiation. Silencing of Blimp1 in
osteoclast precursor cells obviously attenuated the stimulatory effect of TNF
alpha on osteoclastogenesis. Mechanistically, TNF-alpha-induced Blimp1 expression
was markedly rescued by blocking the PI3K/Akt signaling pathway, which suggested
that PI3K/Akt signaling was involved in the regulation of TNF-alpha-stimulated
Blimp1 expression. Taken together, the results established a molecular mechanism
of TNF-alpha-induced osteoclasts differentiation, and provided insights into the
potential contribution of Blimp1 in the regulation of osteoclastogenesis by TNF
alpha. J. Cell. Biochem. 118: 1308-1315, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27505148
TI - Program Directors' Perceptions of Resident Education in Women's Health: A
National Survey.
AB - BACKGROUND: Despite professional societies' emphasis on women's health in
internal medicine (IM) resident curricula, national implementation has varied.
This study describes IM program directors' perceptions of women's health topics
that residents should master and the current state of women's health education in
IM residency programs. MATERIALS AND METHODS: We recruited 408 program directors
of IM residency programs to complete an electronic cross-sectional survey.
Participants were surveyed about expected resident mastery of twelve women's
health topics in the context of their program's current characteristics, core
curricula, and training opportunities. RESULTS: One hundred twelve IM program
directors completed the survey (response rate 27%). The percentage of program
directors who perceived that residents should master each of the twelve women's
health topics ranged from 48% to 98%, with the most program directors expecting
mastery of osteoporosis (N = 110, 98%), sexually transmitted infection (N = 110,
98%), and gender-specific cancer (N = 109, 97%). These topics, however, were not
currently included in the core curricula of 6%-12% of programs. Programs offered
varied opportunities in women's health, including dedicated women's health
electives (N = 76, 68%), concentrations or tracks (N = 8, 7%), and continuity
clinics (N = 15, 13%). Most program directors were interested (N = 90, 80%) in
expanding women's health opportunities in their programs. CONCLUSION: While
women's health topics were perceived by program directors as a priority for IM
resident mastery, certain priority topics and training opportunities were
limited. Additional studies are needed to explore barriers to expansion of
resident education in women's health and potential solutions.
PMID- 27505149
TI - Anxiety, depression and suicide in patients with prurigo nodularis.
PMID- 27505150
TI - Glycemic Control and the Risk of Tuberculosis: A Cohort Study.
AB - BACKGROUND: Diabetes is a well-known risk factor for tuberculosis (TB) and is
increasingly prevalent in low- and middle-income countries, where the burden of
TB is high. Glycemic control has the potential to modify the risk of TB. However,
there are few studies on the association between glycemic control and TB risk,
and the results are inconsistent. METHODS AND FINDINGS: We assembled a cohort
using 123,546 individuals who participated in a community-based health screening
service in northern Taiwan from 5 March 2005 to 27 July 2008. Glycemic control
was measured using fasting plasma glucose (FPG) at the time of screening. The
cohort was followed up to 31 December 2012 for the occurrence of TB by cross
matching the screening database to the national health insurance database.
Multiple imputation was used to handle missing information. During a median
follow-up of 4.6 y, 327 cases of TB occurred. In the multivariable Cox regression
model, diabetic patients with poor glycemic control (FPG > 130 mg/dl) had a
significantly higher hazard of TB (adjusted hazard ratio [aHR] 2.21, 95% CI 1.63
2.99, p < 0.001) compared to those without diabetes. The hazard of TB in diabetic
patients with good glycemic control (FPG <= 130 mg/dl) did not differ
significantly from that in nondiabetic individuals (aHR 0.69, 95% CI 0.35-1.36, p
= 0.281). In the linear dose-response analysis, the hazard of TB increased with
FPG (aHR 1.06 per 10-mg/dl increase in FPG, 95% CI 1.03-1.08, p < 0.001).
Assuming the observed association between glycemic control and TB was causal, an
estimated 7.5% (95% CI 4.1%-11.5%) of incident TB in the study population could
be attributed to poor glycemic control. Limitations of the study include one-time
measurement of fasting glucose at baseline and voluntary participation in the
health screening service. CONCLUSIONS: Good glycemic control could potentially
modify the risk of TB among diabetic patients and may contribute to the control
of TB in settings where diabetes and TB are prevalent.
PMID- 27505151
TI - Music, Spatial Task Performance, and Brain Plasticity in Elderly Adults.
PMID- 27505152
TI - Improved Interfacial Affinity and CO2 Separation Performance of Asymmetric Mixed
Matrix Membranes by Incorporating Postmodified MIL-53(Al).
AB - Asymmetric mixed matrix membranes(MMMs) with MOFs hold great application
potential for energy-efficient gas separations. However, the particle aggregation
and nonselective interfacial microvoids restrict the gas separation performance
of asymmetric MMMs. Herein, nanoporous metal-organic framework (MOF) of MIL
53(Al) was modified with aminosilane after solvothermal synthesis. The
postfunctionalization by grafting alkyl chains can form hydrogen bonds with
polymer chains to enhance the affinity with polymer matrix and facilitate the
preferential adsorption of CO2 by dipole-quadrupole interaction with the
functional group. Then the postmodified MIL-53(Al) was incorporated as filler
into poly(ether imide) Ultem1000 to fabricate high-quality asymmetric MMMs with
well dispersed particles in polymer matrix and good adhesion at the MOFs-polymer
interface. The Ultem/S-MIL-53(Al) asymmetric MMMs exhibited remarkable
combinations of gas permeance and ideal selectivity for CO2/N2 separation at 10
wt % filler loading. The CO2 permeance achieved 24.1 GPU, an increase of 165%
compared with pure Ultem membrane. Meanwhile, the ideal CO2/N2 selectivity also
increased from 31.0 up to 41.1. The strategy of post covalent modification for
MOFs provides an effective way to improve the interfacial affinity and gas
separation performance.
PMID- 27505153
TI - Evaluation of transient elastography in assessing liver fibrosis in patients with
autoimmune hepatitis.
AB - BACKGROUND AND AIM: Transient elastography (TE) can reliably stage liver fibrosis
via liver stiffness measurement (LSM) in chronic liver disease. However, the
accuracy of TE for assessment of liver fibrosis in patients with autoimmune
hepatitis (AIH) is still limited. We evaluate TE in staging liver fibrosis in AIH
patients and compare with other noninvasive diagnostic tools. METHODS: A total of
100 patients with biopsy-proven AIH were included. The correlation between LSM
and fibrosis stage was analyzed using Spearman correlation test. The optimal cut
off values of LSM were calculated for predicting individual fibrosis stages using
receiver-operating characteristic curve. The diagnostic accuracy of LSM for
severe fibrosis was compared with those of serum biochemical scores. RESULTS:
Median LSM in AIH patients was higher than that of healthy controls (11.2 +/- 8.2
kPa vs 4.3 +/- 1.4 kPa, P < 0.01). LSM had significant correlation with fibrosis
(r = 0.752, P < 0.01) and increased progressively with increasing fibrosis stages
in AIH patients. AUROC values of LSM for stages F >= 2, F >= 3, and F4 were 0.878
(95%CI: 0.789-0.967), 0.883 (0.820-0.946), and 0.914 (0.852-0.976), respectively.
The optimal cut-off values of LSM for fibrosis stages F >= 2, F >= 3, and F4 were
6.45, 8.75, and 12.50 kPa, respectively. LSM was superior to APRI score and FIB-4
score in detecting severe fibrosis (F >= 3). Serum ALT levels had minor effect on
LSM values. CONCLUSIONS: Transient elastography is an accurate and reliable
noninvasive tool in assessing liver fibrosis in AIH. Hepatic inflammatory
activity had no significant effect on LSM determination.
PMID- 27505154
TI - When does making detailed predictions make predictions worse?
AB - [Correction Notice: An Erratum for this article was reported in Vol 145(10) of
Journal of Experimental Psychology: General (see record 2016-42695-001). In the
article, the symbols in Figure 2 were inadvertently altered in production. All
versions of this article have been corrected.] In this article, we investigate
whether making detailed predictions about an event worsens other predictions of
the event. Across 19 experiments, 10,896 participants, and 407,045 predictions
about 724 professional sports games, we find that people who made detailed
predictions about sporting events (e.g., how many hits each baseball team would
get) made worse predictions about more general outcomes (e.g., which team would
win). We rule out that this effect is caused by inattention or fatigue, thinking
too hard, or a differential reliance on holistic information about the teams.
Instead, we find that thinking about game-relevant details before predicting
winning teams causes people to give less weight to predictive information,
presumably because predicting details makes useless or redundant information more
accessible and thus more likely to be incorporated into forecasts. Furthermore,
we show that this differential use of information can be used to predict what
kinds of events will and will not be susceptible to the negative effect of making
detailed predictions.
PMID- 27505155
TI - A Power-Law Growth and Decay Model with Autocorrelation for Posting Data to
Social Networking Services.
AB - We propose a power-law growth and decay model for posting data to social
networking services before and after social events. We model the time series
structure of deviations from the power-law growth and decay with a conditional
Poisson autoregressive (AR) model. Online postings related to social events are
described by five parameters in the power-law growth and decay model, each of
which characterizes different aspects of interest in the event. We assess the
validity of parameter estimates in terms of confidence intervals, and compare
various submodels based on likelihoods and information criteria.
PMID- 27505156
TI - Parainfluenza virus 5 upregulates CD55 expression to produce virions with
enhanced resistance to complement-mediated neutralization.
AB - Many enveloped RNA viruses recruit host cell proteins during assembly as a
mechanism to limit antiviral effects of complement. Using viruses which
incorporated CD46 alone, CD55 alone or both CD46 and CD55, we addressed the role
of these two host cell regulators in limiting complement-mediated neutralization
of Parainfluenza virus 5 (PIV5). PIV5 incorporated functional forms of both CD55
and CD46 into virions. PIV5 containing CD55 was highly resistant to complement
mediated neutralization, whereas CD46-containing PIV5 was as sensitive to
neutralization as virus lacking both regulators. PIV5 infected cells had
increased levels of cell surface CD55, which was further upregulated by exogenous
treatment with tumor necrosis factor alpha. PIV5 derived from cells with higher
CD55 levels was more resistant to complement-mediated neutralization in vitro
than virus from control cells. We propose a role for virus induction of host cell
complement inhibitors in defining virus growth and tissue tropism.
PMID- 27505157
TI - Pharmacist-Physician Communications in a Highly Computerised Hospital: Sign-Off
and Action of Electronic Review Messages.
AB - BACKGROUND: Some hospital Computerized Physician Order Entry (CPOE) systems
support interprofessional communication. The aim of this study was to investigate
the effectiveness of pharmacist-physician messages sent via a CPOE system.
METHOD: Data from the year 2012 were captured from a large university teaching
hospital CPOE database on: 1) review messages assigned by pharmacists; 2) details
of the prescription on which the messages were assigned; and 3) details of any
changes made to the prescription following a review message being assigned. Data
were coded for temporal, message and prescription factors. Messages were analysed
to investigate: 1) whether they were signed-off; and 2) the time taken. Messages
that requested a measurable action were further analysed to investigate: 1)
whether they were actioned as requested; and 2) the time taken. We conducted a
multivariable analysis using Generalised Estimating Equations (GEE) to account
for the effects of multiple factors simultaneously, and to adjust for any
potential correlation between outcomes for repeated review messages on the same
prescription. All analyses were performed using SPSS 22 (IBM SPSS Inc., Chicago,
IL, USA), with p<0.05 considered significant. RESULTS: Pharmacists assigned
36,245 review messages to prescriptions over the 12 months, 34,506 of which were
coded for analysis after exclusions. Nearly half of messages (46.6%) were signed
off and 65.5% of these were signed-off in <= 48 hours. Of the 9,991 further
analysed for action, 35.8% led to an action as requested by the pharmacist and
just over half of these (57.0%) were actioned in <= 24 hours. Factors predictive
of an action were the time since the prescription was generated (p<0.001),
pharmacist grade (p<0.001), presence of a high-risk medicine (p<0.001), messages
relating to reconciliation (p = 0.004), theme of communication (p<0.001),
speciality, (p<0.001), category of medicine (p<0.001), and regularity of the
prescription (p<0.001). CONCLUSION: In this study we observed a lower rate of
sign-off and action than we might have expected, suggesting uni-directional
communication via the CPOE system may not be optimal. An established pharmacist
physician collaborative working relationship is likely to influence the
prioritisation and response to messages, since a more desirable outcome was
observed in settings and with grades of pharmacists where this was more likely.
Designing systems that can facilitate collaborative communication may be more
effective in practice.
PMID- 27505158
TI - Nonpathogenic SIV and Pathogenic HIV Infections Associate with Disparate Innate
Cytokine Signatures in Response to Mycobacterium bovis BCG.
AB - Infections with mycobacteria, including Mycobacterium tuberculosis (Mtb) and
Mycobacterium bovis (M. bovis) BCG, are a leading cause of morbidity and
mortality for HIV-infected persons. In contrast to HIV, nonpathogenic SIV
infections of sooty mangabeys are characterized by a lack of clinical disease
including an absence of opportunistic infections. The goal of this study was to
identify innate immune responses to M. bovis BCG maintained during nonpathogenic
lentiviral infections through a comparison of functional responses during
pathogenic HIV or nonpathogenic SIV infections. Monocytes were evaluated for
their ability to express key anti-mycobacterial cytokines TNF-alpha and IL-12
following a six-hour ex vivo BCG exposure. While HIV-infection was associated
with a decreased percentage of IL-12-producing monocytes, nonpathogenic SIV
infection was associated with an increased percentage of monocytes producing both
cytokines. Gene expression analysis of PBMC following ex vivo BCG exposure
identified differential expression of NK cell-related genes and several
cytokines, including IFN-gamma and IL-23, between HIV-infected and control
subjects. In contrast, SIV-infected and uninfected-control mangabeys exhibited no
significant differences in gene expression after BCG exposure. Finally,
differential gene expression patterns were identified between species, with
mangabeys exhibiting lower IL-6 and higher IL-17 in response to BCG when compared
to humans. Overall, this comparison of immune responses to M. bovis BCG
identified unique immune signatures (involving cytokines IL-12, TNF-alpha, IL-23,
IL-17, and IL-6) that are altered during HIV, but maintained or increased during
nonpathogenic SIV infections. These unique cytokine and transcriptome signatures
provide insight into the differential immune responses to Mycobacteria during
pathogenic HIV-infection that may be associated with an increased incidence of
mycobacterial co-infections.
PMID- 27505159
TI - Risk Factors for Stroke in People with End-Stage Kidney Disease: A Cohort Study.
AB - BACKGROUND: It is unclear how traditional cardiovascular risk factors and
different treatment modalities for end-stage kidney disease (ESKD) affect stroke
risk in people with ESKD. We aimed to identify the risk factors for stroke
(ischemic and hemorrhagic) in people with ESKD. METHODS: We conducted a
retrospective cohort study using data linkage between the Australian and New
Zealand Dialysis and Transplant Registry, clinical and administrative datasets.
Using Cox proportional hazards models, we estimated the magnitudes of risk of
hospitalization with different subtypes of strokes associated with traditional
cardiovascular risk factors and ESKD treatment modalities (hemodialysis (HD),
peritoneal dialysis (PD) and kidney transplantation). Results were expressed as
hazard ratios (HRs) with 95% CIs. RESULTS: A total of 10,745 people received
treatment for ESKD in New South Wales, Australia, between 2000 and 2010. We
observed 640 hospitalizations for stroke in 49,497 person-years of follow-up
(129.4 per 10,000 person years). Some risk factors were consistent with those
found in the general population, including smoking and a history of previous
stroke. Other risk factors were novel for people with ESKD. Women were 85% more
likely to have an intracerebral hemorrhage (HR 1.85, 95% CI 1.22-2.79) and 30%
more likely to have an ischemic stroke (HR 1.30, 95% CI 1.01-1.66) than men.
Compared to people on HD, people with kidney transplants had a 65% lower risk of
intracerebral hemorrhage (HR 0.35, 95% CI 0.18-0.69) but a similar risk of
ischemic stroke (HR 0.97, 95% CI 0.64-1.49). People on PD had a 36% higher risk
of ischemic stroke (HR 1.36, 95% CI 1.05-1.76) but a similar risk of
intracerebral hemorrhage compared to people on HD (HR 0.69, 95% CI 0.43-1.11).
CONCLUSIONS: These findings could be used to establish reliable estimates of the
risk of stroke in people with ESKD and identify those who are most likely to
benefit from preventive treatments.
PMID- 27505160
TI - Polarized Cell Division of Chlamydia trachomatis.
AB - Bacterial cell division predominantly occurs by a highly conserved process,
termed binary fission, that requires the bacterial homologue of tubulin, FtsZ.
Other mechanisms of bacterial cell division that are independent of FtsZ are
rare. Although the obligate intracellular human pathogen Chlamydia trachomatis,
the leading bacterial cause of sexually transmitted infections and trachoma,
lacks FtsZ, it has been assumed to divide by binary fission. We show here that
Chlamydia divides by a polarized cell division process similar to the budding
process of a subset of the Planctomycetes that also lack FtsZ. Prior to cell
division, the major outer-membrane protein of Chlamydia is restricted to one pole
of the cell, and the nascent daughter cell emerges from this pole by an
asymmetric expansion of the membrane. Components of the chlamydial cell division
machinery accumulate at the site of polar growth prior to the initiation of
asymmetric membrane expansion and inhibitors that disrupt the polarity of C.
trachomatis prevent cell division. The polarized cell division of C. trachomatis
is the result of the unipolar growth and FtsZ-independent fission of this coccoid
organism. This mechanism of cell division has not been documented in other human
bacterial pathogens suggesting the potential for developing Chlamydia-specific
therapeutic treatments.
PMID- 27505161
TI - Activation of the cAMP Pathway Induces RACK1-Dependent Binding of beta-Actin to
BDNF Promoter.
AB - RACK1 is a scaffolding protein that contributes to the specificity and
propagation of several signaling cascades including the cAMP pathway. As such,
RACK1 participates in numerous cellular functions ranging from cell migration and
morphology to gene transcription. To obtain further insights on the mechanisms
whereby RACK1 regulates cAMP-dependent processes, we set out to identify new
binding partners of RACK1 during activation of the cAMP signaling using a
proteomics strategy. We identified beta-actin as a direct RACK1 binding partner
and found that the association between beta-actin and RACK1 is increased in
response to the activation of the cAMP pathway. Furthermore, we show that cAMP
dependent increase in BDNF expression requires filamentous actin. We further
report that beta-actin associates with the BDNF promoter IV upon the activation
of the cAMP pathway and present data to suggest that the association of beta
actin with BDNF promoter IV is RACK1-dependent. Taken together, our data suggest
that beta-actin is a new RACK1 binding partner and that the RACK1 and beta-actin
association participate in the cAMP-dependent regulation of BDNF transcription.
PMID- 27505162
TI - Cognitive Offloading Does Not Prevent but Rather Promotes Cognitive Development.
AB - We investigate the relation between the development of reactive and cognitive
capabilities. In particular we investigate whether the development of reactive
capabilities prevents or promotes the development of cognitive capabilities in a
population of evolving robots that have to solve a time-delay navigation task in
a double T-Maze environment. Analysis of the experiments reveals that the
evolving robots always select reactive strategies that rely on cognitive
offloading, i.e., the possibility of acting so as to encode onto the relation
between the agent and the environment the states that can be used later to
regulate the agent's behavior. The discovery of these strategies does not
prevent, but rather facilitates, the development of cognitive strategies that
also rely on the extraction and use of internal states. Detailed analysis of the
results obtained in the different experimental conditions provides evidence that
helps clarify why, contrary to expectations, reactive and cognitive strategies
tend to have synergetic relationships.
PMID- 27505163
TI - Do Bioimpedance Measurements of Over-Hydration Accurately Reflect Post
Haemodialysis Weight Changes?
AB - INTRODUCTION: Bioelectrical impedance spectroscopy (BIS) devices are being used
to determine ultrafiltration requirements to achieve target weight for
haemodialysis (HD) patients. Pre-dialysis measurements are more convenient for
both patients and staff. We wished to compare the changes in pre- and post
dialysis hydration measured by BIS with actual weight loss. METHODS: We compared
paired BIS measurements made pre and post HD using a BIS device based on a 3
compartmental model, designed to provide information on extracellular water (ECW)
excess. RESULTS: BIS was measured in 49 HD patients, 35 male (71.4%) with mean
age 67.6 +/- 14.2. Weight fell significantly from 69.2 +/- 17.8 to 67.6 +/- 17.4
kg, and BIS over hydration (OH) from 4.5 +/- 3.3.4 to 3.4 +/- 2.9 litres, and ECW
from 16.8 +/- 4.8 to 15.5 +/- 4.4 litres, but there was no change in the amount
of intracellular water. Weight loss correlated positively with the change in ECW,
but exceeded the fall in OH; mean bias -0.58 (95% confidence limits -3.6 to 4.8
kg). SUMMARY: We measured OH pre and post HD, but did not find that the change in
OH correlated with changes in body weight. Although there was a correlation
between changes in OH and ECW, there was none for weight. Our findings do not
support total reliance on pre-dialysis BIS alone for assessing volume status in
HD patients, but rather BIS should be considered an aid to clinical assessment of
volume status.
PMID- 27505164
TI - Simultaneously saccharification and fermentation approach as a tool for enhanced
fossil fuels biodesulfurization.
AB - Biodesulfurization can be a complementary technology to the hydrodesulfurization,
the commonly physical-chemical process used for sulfur removal from crude oil.
The desulfurizing bacterium Gordonia alkanivorans strain 1B as a fructophilic
microorganism requires fructose as C-source. In this context, the main goal of
this work was the optimization of a simultaneous saccharification and
fermentation (SSF) approach using the Zygosaccharomyces bailii strain Talf1 crude
enzymes with invertase activity and sucrose as a cheaper fructose-rich commercial
C-source (50% fructose) towards dibenzothiophene (DBT) desulfurization by strain
1B. The determination of optimal conditions, for both sucrose hydrolysis and DBT
desulfurization was carried out through two sequential experimental uniform
designs according to the Doehlert distribution for two factors: pH (5.5-7.5) and
temperature (28-38 degrees C), with the enzyme load of 1.16 U/g/L; and enzyme
load (0-4 U/g/L) and temperature (28-38 degrees C), with pH at 7.5. Based on 2
hydroxybiphenyl production, the analysis of the response surfaces obtained
pointed out for pH 7.5, 32 degrees C and 1.8 U/g/L as optimal conditions.
Further optimized SSF of sucrose during the DBT desulfurization process permitted
to attain a 4-fold enhanced biodesulfurization. This study opens a new focus of
research through the exploitation of sustainable low cost sucrose-rich feedstocks
towards a more economical viable bioprocess scale-up.
PMID- 27505165
TI - Sludge reduction by uncoupling metabolism: SBR tests with para-nitrophenol and a
commercial uncoupler.
AB - Nowadays cost reduction is a very important issue in wastewater treatment plants.
One way, is to minimize the sludge production. Microorganisms break down the
organic matter into inorganic compounds through catabolism. Uncoupling metabolism
is a method which promote catabolism reactions instead of anabolism ones, where
adenosine triphosphate synthesis is inhibited. In this work, the influence of the
addition of para-nitrophenol and a commercial reagent to a sequencing batch
reactor (SBR) on sludge production and process performance has been analyzed.
Three laboratory SBRs were operated in parallel to compare the effect of the
addition of both reagents with a control reactor. SBRs were fed with synthetic
wastewater and were operated with the same conditions. Results showed that sludge
production was slightly reduced for the tested para-nitrophenol concentrations
(20 and 25 mg/L) and for a LODOred dose of 1 mL/day. Biological process
performance was not influenced and high COD removals were achieved.
PMID- 27505166
TI - The use of novel packing material for improving methane oxidation in biofilters.
AB - The use of biofilters (working bed volume of 7.85 L) for the oxidation of CH4 at
low concentrations (from 0.17%v/v to 3.63%v/v, typically in waste gas from
anaerobic sewage treatment) was investigated and four empty bed residence times
were tested (in min): 42.8, 29.5, 19.6, and 7.4. Mixtures of organic (composted
leaves) and three non-organic materials (sponge-based material - SBM, blast
furnace slag - BFS, and expanded vermiculite - ExpV) were used as packing media.
Along 188 operational days after the steady state was reached (95 days for start
up), the CH4 mineralization decreased while the inlet loads gradually increased
from 3.0 +/- 0.8 gCH4 m(-3) h(-1) to 148.8 +/- 4.4 gCH4 m(-3) h(-1). The
biofilter packed with ExpV showed the best results, since the CH4 conversions
decreased from 95.0 +/- 5.0% to 12.7 +/- 3.7% as a function of inlet
concentration, compared to the other two biofilters (SBM and BFS) which showed
CH4 conversions decreasing from 56.0 +/- 5.4% to 3.5 +/- 1.2% as a function of
inlet concentration. The methanotrophic activity of biomass taken from ExpV
biofilter was three times higher than the activity of biomass from the other two
biofilters. Taken together, these results suggested that ExpV provides an
attractive environment for microbial growth, besides the mechanical resistance
provided to the whole packing media, showing the potential to its use in
biofiltration of diffuse CH4 emissions.
PMID- 27505167
TI - Characterization of wood mulch and leachate/runoff from three wood recycling
facilities.
AB - Large-scale open storage of wood mulch is common practice at wood recycling
facilities. During rain and snow melt, leachate with soluble compounds and
suspended particles is released from mulch stockpiles. The objective of this
study was to determine the quality of leachate/runoff from wood recycling
facilities to evaluate its potential to contaminate receiving waterbodies. Wood
mulch (n = 30) and leachate/runoff (n = 26) samples were collected over 1.5 years
from three wood recycling facilities in New Jersey, USA. Differences by site were
found (p < 0.05) for most of the 21 constituents tested in the solid wood mulch
samples. Biochemical oxygen demand (range <20-3000 mg/L), chemical oxygen demand
(134-6000 mg/L) and total suspended solids (69-401 mg/L) median concentrations of
the leachate/runoff samples were comparable to those of untreated domestic
wastewater. Total Kjeldahl N, total P and fecal coliform median values were
slightly lower than typical wastewater values. Dose-response studies with
leachate/runoff samples using zebrafish (Danio rerio) embryos showed that
mortality and developmental defects typically did not occur even at the highest
concentration tested, indicating low toxicity, although delayed development did
occur. Based on this study, leachate/runoff from wood recycling facilities should
not be released to surface waters as it is a potential source of organic
contamination and low levels of nutrients. A study in which runoff from a
controlled drainage area containing wood mulch of known properties is monitored
would allow for better assessment of the potential impact of stormwater runoff
from wood recycling facilities.
PMID- 27505168
TI - Natural Cubic Spline Regression Modeling Followed by Dynamic Network
Reconstruction for the Identification of Radiation-Sensitivity Gene Association
Networks from Time-Course Transcriptome Data.
AB - Gene expression time-course experiments allow to study the dynamics of
transcriptomic changes in cells exposed to different stimuli. However, most
approaches for the reconstruction of gene association networks (GANs) do not
propose prior-selection approaches tailored to time-course transcriptome data.
Here, we present a workflow for the identification of GANs from time-course data
using prior selection of genes differentially expressed over time identified by
natural cubic spline regression modeling (NCSRM). The workflow comprises three
major steps: 1) the identification of differentially expressed genes from time
course expression data by employing NCSRM, 2) the use of regularized dynamic
partial correlation as implemented in GeneNet to infer GANs from differentially
expressed genes and 3) the identification and functional characterization of the
key nodes in the reconstructed networks. The approach was applied on a time
resolved transcriptome data set of radiation-perturbed cell culture models of non
tumor cells with normal and increased radiation sensitivity. NCSRM detected
significantly more genes than another commonly used method for time-course
transcriptome analysis (BETR). While most genes detected with BETR were also
detected with NCSRM the false-detection rate of NCSRM was low (3%). The GANs
reconstructed from genes detected with NCSRM showed a better overlap with the
interactome network Reactome compared to GANs derived from BETR detected genes.
After exposure to 1 Gy the normal sensitive cells showed only sparse response
compared to cells with increased sensitivity, which exhibited a strong response
mainly of genes related to the senescence pathway. After exposure to 10 Gy the
response of the normal sensitive cells was mainly associated with senescence and
that of cells with increased sensitivity with apoptosis. We discuss these results
in a clinical context and underline the impact of senescence-associated pathways
in acute radiation response of normal cells. The workflow of this novel approach
is implemented in the open-source Bioconductor R-package splineTimeR.
PMID- 27505170
TI - High-Efficiency Microiterative Optimization in QM/MM Simulations of Large
Flexible Systems.
AB - We present here a double-optimizations-of-buffer-region (DOBR) microiterative
scheme for high-efficiency energy minimizations of large, flexible systems in
combined quantum-mechanical/molecular-mechanical (QM/MM) calculations. In the
DOBR scheme, an entire system is divided into three regions: the core, buffer,
and outer regions. The core region includes QM atoms and the MM atoms within a
cutoff distance R1 to the QM atoms (denoted by MM1 atoms), and the buffer region
consists of MM atoms within another cutoff distance R2 to MM1 atoms. Each DOBR
microcycle involves two steps: First, QM atoms are assigned electrostatic
potential (ESP) charges, and the buffer and outer regions are optimized at the MM
level with the core region kept frozen. Second, the core and buffer regions are
optimized at the QM/MM level using the electrostatic embedding with the outer
region kept frozen. The two steps are repeated until two optimizations converge
at one structure. The DOBR scheme was tested in the optimizations of nucleobases
solvated in water spheres of 30 A radius, where the initial geometries were
extracted from the trajectories of classical molecular dynamics simulations, and
the cutoff distances R1 and R2 were set to 5.0 and 4.0 A, respectively. For
comparisons, the optimizations were also carried out by a "standard" scheme
without microiteration and by the two-region microiterative (TRM) method. We
found that the averaged number of QM calculations for the DOBR scheme is only ~1%
of that of the standard scheme and ~6% of the TRM approach. The promising results
indicate that the DOBR scheme could significantly increase the efficiency of
geometry optimizations for large, flexible systems in QM/MM calculations.
PMID- 27505169
TI - Dendritic Cells from HIV Controllers Have Low Susceptibility to HIV-1 Infection
In Vitro but High Capacity to Capture HIV-1 Particles.
AB - HIV controllers (HICs), rare HIV-1 infected individuals able to control viral
replication without antiretroviral therapy, are characterized by an efficient
polyfunctional and cytolytic HIV-specific CD8+ T cell response. The mechanisms
underlying the induction and maintenance of such response in many HICs despite
controlled viremia are not clear. Dendritic cells play a crucial role in the
generation and reactivation of T cell responses but scarce information is
available on those cells in HICs. We found that monocyte derived dendritic cells
(MDDCs) from HICs are less permissive to HIV-1 infection than cells from healthy
donors. In contrast MDDCs from HICs are particularly efficient at capturing HIV-1
particles when compared to cells from healthy donors or HIV-1 patients with
suppressed viral load on antiretroviral treatment. MDDCs from HICs expressed on
their surface high levels of syndecan-3, DC-SIGN and MMR, which could cooperate
to facilitate HIV-1 capture. The combination of low susceptibility to HIV-1
infection but enhanced capacity to capture particles might allow MDDCs from HICs
to preserve their function from the deleterious effect of infection while
facilitating induction of HIV-specific CD8+ T cells by cross-presentation in a
context of low viremia.
PMID- 27505171
TI - Accumulation of Advanced Glycation End Products Involved in Inflammation and
Contributing to Severe Preeclampsia, in Maternal Blood, Umbilical Blood and
Placental Tissues.
AB - OBJECTIVE: To investigate the expression of advanced glycation end products
(AGEs) and the receptor for AGE (RAGEs) in maternal blood, umbilical blood and
placental tissues in women with severe preeclampsia (sPE) as well as any
association with inflammatory processes. METHODS: The expressions of AGEs, RAGE,
tumor necrosis factor-alpha (TNF)-alpha and vascular cell adhesion molecule-1
(VCAM)-1 in placental tissues were measured using immunohistochemistry. The
levels of AGEs, RAGE, TNF-alpha and VCAM-1 in maternal blood, umbilical blood and
placental extracts were assessed using enzyme-linked immunosorbent assays.
Placental RAGE, TNF-alpha and VCAM-1 mRNA expression levels were determined by
PCR. Placental AGEs, RAGE, TNF-alpha and VCAM-1 protein levels were determined by
western blotting. RESULTS: The levels of AGEs, TNF-alpha and VCAM-1 in the
maternal tissues and umbilical blood were significantly higher in the sPE group
than in the normal pregnancy (NP) controls (p < 0.05). The serum level of sRAGE
in the umbilical blood was lower in the sPE group than in the NP controls (p <
0.05), while sRAGE was higher in the maternal blood of sPE than in the NP (p <
0.05). The maternal serum levels of AGEs were positively correlated with that of
TNF-alpha and VCAM-1 in the maternal blood. There were no correlations between
the levels of RAGE, TNF-alpha or VCAM-1 in maternal blood or umbilical serum.
There were no correlations between the levels of sRAGE and TNF-alpha or VCAM-1 in
maternal blood or umbilical serum. The levels of AGEs were positively correlated
with those of TNF-alpha and VCAM-1 in placental lysates. CONCLUSION: AGEs and
RAGE appear to act as important mediators in regulating the inflammatory pathways
of preeclampsia.
PMID- 27505172
TI - On the Apportionment of Population Structure.
AB - Measures of population differentiation, such as FST, are traditionally derived
from the partition of diversity within and between populations. However, the
emergence of population clusters from multilocus analysis is a function of
genetic structure (departures from panmixia) rather than of diversity. If the
populations are close to panmixia, slight differences between the mean pairwise
distance within and between populations (low FST) can manifest as strong
separation between the populations, thus population clusters are often evident
even when the vast majority of diversity is partitioned within populations rather
than between them. For any given FST value, clusters can be tighter (more
panmictic) or looser (more stratified), and in this respect higher FST does not
always imply stronger differentiation. In this study we propose a measure for the
partition of structure, denoted EST, which is more consistent with results from
clustering schemes. Crucially, our measure is based on a statistic of the data
that is a good measure of internal structure, mimicking the information extracted
by unsupervised clustering or dimensionality reduction schemes. To assess the
utility of our metric, we ranked various human (HGDP) population pairs based on
FST and EST and found substantial differences in ranking order. EST ranking seems
more consistent with population clustering and classification and possibly with
geographic distance between populations. Thus, EST may at times outperform FST in
identifying evolutionary significant differentiation.
PMID- 27505174
TI - Design, Characterization, and Use of a Novel Amyloid beta-Protein Control for
Assembly, Neurotoxicity, and Gene Expression Studies.
AB - A key pathogenic agent in Alzheimer's disease (AD) is the amyloid beta-protein
(Abeta), which self-assembles into a variety of neurotoxic structures.
Establishing structure-activity relationships for these assemblies, which is
critical for proper therapeutic target identification and design, requires
aggregation and neurotoxicity experiments that are properly controlled with
respect to the Abeta peptide itself. "Reverse" Abeta or non-Abeta peptides suffer
from the fact that their biophysical properties are too similar or dissimilar,
respectively, to those of native Abeta for them to be appropriate controls. For
this reason, we used simple protein design principles to create scrambled Abeta
peptides predicted to behave distinctly from native Abeta. We showed that our
prediction was true by monitoring secondary structure dynamics with thioflavin T
fluorescence and circular dichroism spectroscopy, determining oligomer size
distributions, and assaying neurotoxic activity. We then demonstrated the utility
of the scrambled Abeta peptides by using them to control experiments examining
the effects of Abeta monomers, dimers, higher-order oligomers, and fibrils on
gene expression in primary rat hippocampal neurons. Significant changes in gene
expression were observed for all peptide assemblies, but fibrils induced the
largest changes. Weighted gene co-expression network analysis revealed two
predominant gene modules related to Abeta treatment. Many genes within these
modules were associated with inflammatory signaling pathways.
PMID- 27505175
TI - Depth-Profiling Electronic and Structural Properties of Cu(In,Ga)(S,Se)2 Thin
Film Solar Cell.
AB - Utilizing a scanning photoelectron microscope (SPEM) and grazing-incidence X-ray
powder diffraction (GIXRD), we studied the electronic band structure and the
crystalline properties of the pentanary Cu(In,Ga)(S,Se)2 (CIGSSe) thin-film solar
cell as a function of sample depth on measuring the thickness-gradient sample. A
novel approach is proposed for studying the depth-dependent information on thin
films, which can provide a gradient thickness and a wide cross-section of the
sample by polishing process. The results exhibit that the CIGSSe absorber layer
possesses four distinct stoichiometries. The growth mechanism of this distinctive
compositional distribution formed by a two-stage process is described according
to the thermodynamic reaction and the manufacturing process. On the basis of the
depth-profiling results, the gradient profiles of the conduction and valence
bands were constructed to elucidate the performance of the electrical properties
(in this case, Voc = 620 mV, Jsc = 34.6 mA/cm(2), and eta = 14.04%); the valence
band maxima (VBM) measured with a SPEM in the spectroscopic mode coincide with
this band-structure model, except for a lowering of the VBM observed in the
surface region of the absorber layer due to the ordered defect compound (ODC). In
addition, the depth-dependent texturing X-ray diffraction pattern presents the
crystalline quality and the residual stress for each depth of a thin-film device.
We find that the randomly oriented grains in the bottom region of the absorber
layer and the different residual stress between the underlying Mo and the
absorber interface, which can deteriorate the electrical performance due to
peeling-off effect. An anion interstitial defect can be observed on comparing the
anion concentration of the elemental distribution with crystalline composition; a
few excess sulfur atoms insert in interstitial sites at the front side of the
absorber layer, whereas the interstitial selenium atoms insert at the back side.
PMID- 27505176
TI - Comparison of Holmium: YAG Laser and Pneumatic Lithotripsy in the Treatment of
Ureteral Stones: An Update Meta-Analysis.
AB - PURPOSE: Holmium YAG laser lithotripsy (LL) and pneumatic lithotripsy (PL) are
the most commonly used procedures in the treatment of ureteral calculi. In a
previous meta-analysis examining the treatment effect of the 2 modalities, the
authors highlighted the need for large sample size and high quality trials to
provide more uncovered outcome. Recently, several randomized controlled trials
(RCTs) evaluating the same issue with larger patient number and more complicated
data have been published. Therefore, we conducted this meta-analysis to update
and synthesize evidence on the efficacy and safety of the 2 procedures in the
treatment of ureteral calculi. METHODS: The relevant studies were identified by
searching Medline, EMBASE and Cochrane Library Database from January 1990 to
November 2015. RCTs assessing the efficacy and safety of Holmium YAG laser and PL
for ureteral stones were included. Two reviewers independently screened studies
and extracted data. RESULTS: A total of 8 studies were identified including 1,555
patients. Compared with PL, Holmium YAG LL significantly reduced the mean
operative time (weighted mean difference = -11.52, 95% CI -17.06 to -5.99, p <
0.0001) and increased the early stone-free rate (OR 2.69, 95% CI 1.91-3.78, p <
0.00001) and the delayed stone-free rate (OR 2.12, 95% CI 1.40-3.21, p = 0.0004).
However, a higher postoperative ureteral stricture rate (OR 3.38, 95% CI 1.56
7.31, p = 0.002) was observed in LL group over PL group. There was no statistical
significance in the ureteral perforation rate (OR 1.19, 95% CI 0.65-2.16, p =
0.58), the stone migration rate (OR 0.64, 95% CI 0.41-1.00, p = 0.05), the
postoperative gross hematuria rate (OR 0.71, 95% CI 0.40-1.25, p = 0.23) and the
postoperative fever rate (OR 0.73, 95% CI 0.50-1.09, p = 0.12). CONCLUSIONS: Our
data reconfirmed that Holmium LL for ureteral stones can achieve shorter mean
operative time, better early and delayed stone-free rate with larger sample size
and more high quality studies. And further trials are unlikely to considerably
alter this conclusion. In terms of higher risk of postoperative ureteral
stricture in LL group over PL group observed in our review, more high quality,
multicenter RCTs with long-term follow-up outcome are warranted to better assess
this issue.
PMID- 27505177
TI - Spotlights on our sister journals: Chem. Eur. J. 34/2016.
PMID- 27505173
TI - Transcriptional Profiling of Cultured, Embryonic Epicardial Cells Identifies
Novel Genes and Signaling Pathways Regulated by TGFbetaR3 In Vitro.
AB - The epicardium plays an important role in coronary vessel formation and Tgfbr3-/-
mice exhibit failed coronary vessel development associated with decreased
epicardial cell invasion. Immortalized Tgfbr3-/- epicardial cells display the
same defects. Tgfbr3+/+ and Tgfbr3-/- cells incubated for 72 hours with VEH or
ligands known to promote invasion via TGFbetaR3 (TGFbeta1, TGFbeta2, BMP2), for
72 hours were harvested for RNA-seq analysis. We selected for genes >2-fold
differentially expressed between Tgfbr3+/+ and Tgfbr3-/- cells when incubated
with VEH (604), TGFbeta1 (515), TGFbeta2 (553), or BMP2 (632). Gene Ontology (GO)
analysis of these genes identified dysregulated biological processes consistent
with the defects observed in Tgfbr3-/- cells, including those associated with
extracellular matrix interaction. GO and Gene Regulatory Network (GRN) analysis
identified distinct expression profiles between TGFbeta1-TGFbeta2 and VEH-BMP2
incubated cells, consistent with the differential response of epicardial cells to
these ligands in vitro. Despite the differences observed between Tgfbr3+/+ and
Tgfbr3-/- cells after TGFbeta and BMP ligand addition, GRNs constructed from
these gene lists identified NF-KB as a key nodal point for all ligands examined.
Tgfbr3-/- cells exhibited decreased expression of genes known to be activated by
NF-KB signaling. NF-KB activity was stimulated in Tgfbr3+/+ epicardial cells
after TGFbeta2 or BMP2 incubation, while Tgfbr3-/- cells failed to activate NF-KB
in response to these ligands. Tgfbr3+/+ epicardial cells incubated with an
inhibitor of NF-KB signaling no longer invaded into a collagen gel in response to
TGFbeta2 or BMP2. These data suggest that NF-KB signaling is dysregulated in
Tgfbr3-/- epicardial cells and that NF-KB signaling is required for epicardial
cell invasion in vitro. Our approach successfully identified a signaling pathway
important in epicardial cell behavior downstream of TGFbetaR3. Overall, the genes
and signaling pathways identified through our analysis yield the first
comprehensive list of candidate genes whose expression is dependent on TGFbetaR3
signaling.
PMID- 27505178
TI - Initiation time of renal replacement therapy on patients with acute kidney
injury: A systematic review and meta-analysis of 8179 participants.
AB - The early initiation of renal replacement therapy has been recommended for
patients with acute renal failure by some studies, but its effects on mortality
and renal recovery are unknown. We conducted an updated meta-analysis to provide
quantitative evaluations of the association between the early initiation of renal
replacement therapy and mortality for patients with acute kidney injury. After
applying inclusion/exclusion criteria, 51 studies, including 10 randomized
controlled trials, with a total of 8179 patients were analyzed. Analysis of the
included trials showed that patients receiving early renal replacement therapy
had a 25% reduction in all-cause mortality compared to those receiving late renal
replacement therapy (risk ratio [RR] 0.75, 95% CI [0.69, 0.82]). We also noted a
30% increase in renal recovery (RR 1.30, 95% CI [1.07, 1.56]), a reduction in
hospitalization of 5.84 days (mean difference [MD], 95% CI [-10.27, -1.41]) and a
reduction in the duration of mechanical ventilation of 2.33 days (MD, 95% CI [
3.40, -1.26]) in patients assigned to early renal replacement therapy. The early
initiation of renal replacement therapy was associated with a decreased risk of
all-cause mortality compared with the late initiation of RRT in patients with
acute kidney injury. These findings should be interpreted with caution given the
heterogeneity between studies. Further studies are needed to identify the causes
of mortality and to assess whether mortality differs by dialysis dose.
PMID- 27505179
TI - [Access to medicines for Alzheimer's disease provided by the Brazilian Unified
National Health System in Minas Gerais State, Brazil].
AB - This study evaluated barriers to access to treatment for Alzheimer's disease
based on administrative cases involving cholinesterase inhibitors (ChEIs) and
submitted to the Minas Gerais State Health Secretariat in Brazil in 2012 and
2013. Drawing on data from 165 randomly selected cases, the study addressed the
following dimensions of access: geographic accessibility, accommodation,
acceptability, availability, and affordability. The administrative processing to
supply ChEIs took an average of 39 days and was influenced by characteristics of
the path taken by the user. The majority of the prescribers met less than 80% of
the required criteria in the Clinical Protocol and Therapeutic Guidelines (CPTG)
for Alzheimer's disease. As a result, 38% of requests for medication were denied.
Private treatment with ChEIs cost the equivalent of 21 days of the monthly
minimum wage. In conclusion, bureaucratic administrative procedures and
prescribers' difficulty in following the CPTG hindered access to treatment of
Alzheimer's disease and imposed a heavy burden on patients' pockets.
PMID- 27505180
TI - Microchemical Pen: An Open Microreactor for Region-Selective Surface
Modification.
AB - Various micro surface-modification approaches including photolithography, dip-pen
lithography and ink-jet systems have been developed and used to extend the
functionalities of solid surfaces. While those approaches work in the "open
space", push-pull systems which work in solutions have recently drawn
considerable attention. However, the confining flows performed by push-pull
systems have realized only the dispense process, while microscale, region
selective chemical reactions have remained unattainable. This study reports a
microchemical pen that enables region-selective chemical reactions for the micro
surface modification/patterning. The chemical pen is based on the principle of
microfluidic laminar flows and the resulting mixing of reagents by the mutual
diffusion. The tiny diffusion layer performs as the working region. This report
represents the first demonstration of an open microreactor in which two different
reagents react on a real solid sample. The multifunctional characteristics of the
microchemical pen are confirmed by different types of reactions in many research
areas, including inorganic chemistry, polymer science, electrochemistry and
biological sample treatment.
PMID- 27505182
TI - Rescue of Premature Coronal Suture Fusion with TGF-beta2 Neutralizing Antibody in
Rabbits with Delayed-Onset Synostosis.
AB - OBJECTIVES: An overexpression of Tgf-beta2 leads to calvarial hyperostosis and
suture fusion in individuals with craniosynostosis. Inhibition of Tgf-beta2 may
help rescue fusing sutures and restore normal growth. The present study was
designed to test this hypothesis. DESIGN: Twenty-eight New Zealand White rabbits
with delayed-onset coronal synostosis had radiopaque markers placed on either
side of the coronal sutures at 10 days of age. The rabbits were randomly assigned
to: (1) sham control rabbits (n = 10), (2) rabbits with control IgG (100
MUg/suture) delivered in a collagen vehicle (n = 9), and (3) rabbits with Tgf
beta2 neutralizing antibody (100 MUg/suture) delivered in a collagen vehicle (n =
9). Longitudinal growth data were collected at 10, 25, 42, and 84 days of age.
Sutures were harvested at 84 days of age for histomorphometry. RESULTS:
Radiographic analysis showed significantly greater ( P < .05) coronal suture
marker separation, craniofacial length, cranial vault length, height, shape
indices, cranial base length, and more lordotic cranial base angles in rabbits
treated with anti-Tgf-beta2 antibody than in controls at 42 and 84 days of age.
Histologically, rabbits treated with anti-Tgf-beta2 antibody at 84 days of age
had patent and significantly ( P < .05) wider coronal sutures and greater sutural
area compared to controls. CONCLUSIONS: These data support our hypothesis that
antagonism of Tgf-beta2 may rescue fusing coronal sutures and facilitate
craniofacial growth in this rabbit model. These findings also suggest that
cytokine therapy may have clinical significance in infants with progressive
postgestational craniosynostosis.
PMID- 27505181
TI - Hypertelorism and Orofacial Clefting Revisited: An Anthropometric Investigation.
AB - OBJECTIVE: Since the 1960s, multiple studies have reported a tendency toward
hypertelorism in individuals with nonsyndromic orofacial clefts (OFCs). However,
the association between specific cleft types and increased interorbital distance
has been inconsistent. Using three-dimensional (3D) surface imaging, we tested
whether different forms of clefting showed evidence of increased interorbital
distance. METHODS: Intercanthal and outercanthal distances and intercanthal
indices were calculated from 3D facial surface images of 287 individuals with
repaired OFCs. Raw measurements were converted to sex and age-normalized Z
scores. Mean Z-scores for individuals with cleft lip (CL), cleft lip and palate
(CLP), and cleft palate (CP) were compared with reference normative values
(controls) and one another directly using t tests and analysis of variance.
RESULTS: The CLP group showed a significant increase in intercanthal width (P =
.001) and intercanthal index (P < .001) compared with reference norms. The CP
group showed a significant decrease (P < .001) in outercanthal width. The CL
group showed no difference from reference norms. The proportion of clinically
hyperteloric individuals was generally low but highest in the CLP group (7.4%).
Cleft severity had little effect on interorbital spacing. CONCLUSIONS:
Individuals with CLP exhibited on average a tendency toward mild hypertelorism,
driven primarily by an increase in intercanthal distance. This tendency was not
seen in CL or CP.
PMID- 27505183
TI - A virtually 1H-free birdcage coil for zero echo time MRI without background
signal.
AB - PURPOSE: MRI of tissues with rapid transverse relaxation can be performed
efficiently using the zero echo time (ZTE) technique. At high bandwidths leading
to large relative initial radiofrequency (RF) dead times, the method becomes
increasingly sensitive to artifacts related to signal stemming from outside the
field of view, particularly from the RF coils. Therefore, in this work, a
birdcage coil was designed that is virtually free of 1H signal. METHODS: A
transmit-receive birdcage RF coil for MRI of joints at 7T was designed by
rigorously avoiding materials containing 1H nuclei, by using purely mechanical
connections without glue, and by spoiling of unwanted signal by application of
ferromagnetic materials. The coil was tested for residual 1H signal using ZTE
phantom and in vivo joint imaging. RESULTS: In standard ZTE imaging, no 1H signal
was detected above noise level. Only at extreme averaging, residual signal was
observed close to conductors associated with 1H-containing molecules at adjacent
glass surfaces. Phantom images with dead times up to 3.8 Nyquist dwells were
obtained with only negligible background artifacts. Furthermore, high-quality ZTE
images of human joints were acquired. CONCLUSION: A virtually 1H-free birdcage
coil is presented, thus enabling in vivo ZTE MRI practically free of background
signal, even at high bandwidths. Magn Reson Med 78:399-407, 2017. (c) 2016
International Society for Magnetic Resonance in Medicine.
PMID- 27505184
TI - Indeterminate but Likely Unimportant Extracolonic Findings at Screening CT
Colonography (C-RADS Category E3): Incidence and Outcomes Data From a Clinical
Screening Program.
AB - OBJECTIVE: The purpose of this study was to analyze the incidence and outcomes of
unsuspected indeterminate but likely unimportant extracolonic findings (CT
Colonography Reporting and Data System [C-RADS] category E3) at screening CT
colonography (CTC). MATERIALS AND METHODS: Over 99 months (April 2004 through
June 2012), 7952 consecutive adults without symptoms of colorectal cancer (4277
women, 3675 men; mean age +/- SD, 56.7 +/- 7.3 years) underwent first-time
screening CTC. Findings prospectively placed into C-RADS category E3 were
retrospectively reviewed, including follow-up (range, 2-10 years) and ultimate
clinical outcome. RESULTS: Unsuspected C-RADS category E3 extracolonic findings
were detected in 9.1% (725/7952) of our patient population. A total of 751
category E3 findings were detected among these 725 patients; 25 patients had
multiple findings. Commonly involved organ systems included gynecologic (24.4%,
183/751), genitourinary (20.9%, 157/751), lung (20.6%, 155/751), and
gastrointestinal (16.1%, 121/751). Consideration for further imaging, if
clinically warranted, was suggested in 83.8% (608/725). Sixty-five patients were
lost to follow-up. Conditions requiring treatment or surveillance were ultimately
diagnosed in 8.3% (55/660), including eight malignant neoplasms. In the remaining
605 patients, 25 (4.1%) underwent invasive biopsy or surgery to prove benignity
(including 18 complex adnexal masses), and 278 (46.0%) received additional
imaging follow-up. CONCLUSION: Indeterminate but likely unimportant extracolonic
findings (C-RADS category E3) occurred in less than 10% of adults without
symptoms of colorectal cancer who underwent screening CTC. Over 90% of these
findings ultimately proved to be clinically insignificant, with fewer than 5%
requiring an invasive procedure to prove benign disease, the majority of which (>
70%) were complex adnexal lesions in women.
PMID- 27505185
TI - Endothelial Nitric Oxide Synthase Prevents Heparanase Induction and the
Development of Proteinuria.
AB - Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and
renal injury in several glomerular diseases, but the underlying mechanism is not
fully understood. We recently showed that heparanase is essential for the
development of experimental diabetic nephropathy and glomerulonephritis, and
hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate
that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice
leads to an increased glomerular heparanase expression accompanied with overt
proteinuria, which was not observed in the AN-resistant wild type counterpart. In
vitro, the eNOS inhibitor asymmetric dimethylarginine (ADMA) induced heparanase
expression in cultured mouse glomerular endothelial cells. Moreover, ADMA
enhanced transendothelial albumin passage in a heparanase-dependent manner. We
conclude that eNOS prevents heparanase induction and the development of
proteinuria.
PMID- 27505186
TI - Associations between Mental Health and Ebola-Related Health Behaviors: A
Regionally Representative Cross-sectional Survey in Post-conflict Sierra Leone.
AB - BACKGROUND: Little attention has been paid to potential relationships between
mental health, trauma, and personal exposures to Ebola virus disease (EVD) and
health behaviors in post-conflict West Africa. We tested a conceptual model
linking mental health and trauma to EVD risk behaviors and EVD prevention
behaviors. METHODS AND FINDINGS: Using survey data from a representative sample
in the Western Urban and Western Rural districts of Sierra Leone, this study
examines associations between war exposures, post-traumatic stress disorder
(PTSD) symptoms, depression, anxiety, and personal EVD exposure (e.g., having
family members or friends diagnosed with EVD) and EVD-related health behaviors
among 1,008 adults (98% response rate) from 63 census enumeration areas of the
Western Rural and Western Urban districts randomly sampled at the height of the
EVD epidemic (January-April 2015). Primary outcomes were EVD risk behaviors (14
items, Cronbach's alpha = 0.84) and EVD prevention behaviors (16 items,
Cronbach's alpha = 0.88). Main predictors comprised war exposures (8 items,
Cronbach's alpha = 0.85), anxiety (10 items, Cronbach's alpha = 0.93), depression
(15 items, Cronbach's alpha = 0.91), and PTSD symptoms (16 items, Cronbach's
alpha = 0.93). Data were analyzed using two-level, population-weighted
hierarchical linear models with 20 multiply imputed datasets. EVD risk behaviors
were associated with intensity of depression symptoms (b = 0.05; 95% CI 0.00,
0.10; p = 0.037), PTSD symptoms (b = 0.10; 95% CI 0.03, 0.17; p = 0.008), having
a friend diagnosed with EVD (b = -0.04; 95% CI -0.08, -0.00; p = 0.036), and war
exposures (b = -0.09; 95% CI -0.17, -0.02; p = 0.013). EVD prevention behaviors
were associated with higher anxiety (b = 0.23; 95% CI 0.06, 0.40; p = 0.008),
having a friend diagnosed with EVD (b = 0.15; 95% CI 0.04, 0.27; p = 0.011), and
higher levels of war exposure (b = 0.45; 95% CI 0.16, 0.74; p = 0.003),
independent of mental health. PTSD symptoms were associated with lower levels of
EVD prevention behavior (b = -0.24; 95% CI -0.43, -0.06; p = 0.009). CONCLUSIONS:
In post-conflict settings, past war trauma and mental health problems are
associated with health behaviors related to combatting EVD. The associations
between war trauma and both EVD risk behaviors and EVD prevention behaviors may
be mediated through two key mental health variables: depression and PTSD
symptoms. Considering the role of mental health in the prevention of disease
transmission may help fight continuing and future Ebola outbreaks in post
conflict Sierra Leone. This sample is specific to Freetown and the Western Area
and may not be representative of all of Sierra Leone. In addition, our main
outcomes as well as personal EVD exposure, war exposures, and mental health
predictors rely on self-report, and therefore raise the possibility of common
methods bias. However, the findings of this study may be relevant for
understanding dynamics related to EVD and mental health in other major capital
cities in the EVD-affected countries of West Africa.
PMID- 27505187
TI - Affective instability as a clinical feature of avoidant personality disorder.
AB - The current study's main goal was to examine whether affective instability is
elevated among individuals suffering from avoidant personality disorder (APD) by
comparing it to the affective instability found among individuals suffering from
borderline personality disorder (BPD) as well that found among healthy controls.
Adults (N = 152, aged 18-65 years) with BPD, APD, or no psychopathology
participated in a 3-week computerized diary study. We examined temporal
instability in negative affect using experience-sampling methods. Both within and
between days, individuals with APD showed greater affective instability compared
to the healthy control individuals, although less affective instability compared
to individuals with BPD. The findings are in line with affective instability (or
emotional lability) as a key dimension relevant across personality disorders.
Additionally, they emphasize the need for research and clinical attention to
affective characteristics (alongside the more readily recognized interpersonal
characteristics) of APD. (PsycINFO Database Record
PMID- 27505188
TI - Ecological momentary assessment of nonsuicidal self-injury in youth with
borderline personality disorder.
AB - Nonsuicidal self-injury (NSSI) is highly prevalent among individuals with
borderline personality disorder (BPD). The aim of this study was to investigate
the cognitive, emotional, and contextual experience of NSSI in 107 youth (aged 15
25 years) with BPD who had minimal prior exposure to treatment. Using ecological
momentary assessment, participants completed a randomly prompted questionnaire
about their affect, self-injurious thoughts, and behaviors six times per day for
6 days. Twenty-four youth with BPD engaged in 52 counts of NSSI, with 56 motives
identified. Open-ended questions revealed that on occasions of NSSI, a large
minority of participants could identify neither their motives (27%, n = 15) nor
the environmental precipitants (46%, n = 24) for NSSI. Changes in affect revealed
a pattern of increasing negative and decreasing positive affect prior to NSSI,
with a reduction in negative and an increase in positive affect following NSSI.
These changes were absent for those who did not engage in NSSI. Initial self
injurious thoughts and changes in negative and positive affect occurred a median
of 35, 15, and 10 hr prior to NSSI, respectively. These findings suggest that
youth with BPD have limited capacity to reflect on their motives and environment
preceding NSSI. The patterns of affect change indicate that NSSI is maintained by
reward incentives as well as negative reinforcement. The time between initial
self-injurious thoughts and engagement in NSSI reveals a window of opportunity
for intervention. (PsycINFO Database Record
PMID- 27505189
TI - Loneliness, social networks, and social functioning in borderline personality
disorder.
AB - Persistent loneliness is often reported by patients with borderline personality
disorder (BPD). However, empirical studies investigating this aspect of BPD
psychopathology are sparse. Studies from social psychology revealed that social
isolation and low social functioning contribute to loneliness, that is, the
subjective feeling of being alone. The aim of the present study was to contribute
to the understanding of loneliness in BPD by investigating its relation to social
isolation and functioning in different domains of life. Subjective experience of
loneliness was measured in 80 women (40 BPD patients, 40 healthy controls) with
the UCLA Loneliness Scale. Social isolation and social functioning were assessed
with the Social Network Inventory and the Social Functioning Scale. In addition,
we assessed global functioning with the Global Assessment of Functioning. BPD
patients reported stronger feelings of loneliness compared to healthy
participants. In general, the level of loneliness was linked to network size,
social engagement, and prosocial behavior. Diversity of social networks and
functioning in the domain of interpersonal communication were associated with the
level of loneliness only in BPD. A reduced variety of roles in social life
together with impairments in interpersonal communication were particularly
relevant for the experience of loneliness in BPD, suggesting an indirect path to
target this psychopathological feature in therapeutic interventions. However,
both social isolation and social functioning were not sufficient to explain the
severely increased loneliness experienced by these patients, stressing the need
for further investigation of determinants of loneliness in this clinical
population. (PsycINFO Database Record
PMID- 27505190
TI - Insight and the Dark Triad: Comparing self- and meta-perceptions in relation to
psychopathy, narcissism, and Machiavellianism.
AB - The "Dark Triad" consists of 3 partially overlapping trait configurations that
manifest in problematic interpersonal outcomes: narcissism, psychopathy, and
Machiavellianism. Comparing meta-perception-based reports of personality, or how
people believe others see them, to self-reports in relation to informant-reports
allows for a direct test of the extent to which people are accurate in
understanding how they are perceived by others. The present study (n = 993 target
participants) investigated how Dark Triad personality styles are viewed from
multiple perspectives, including self-report, meta-perception, informant-report
(n = 213), and informant perceived meta-perception (n = 178) in an undergraduate
sample. Absolute level differences were investigated; self-report ratings were
associated with significantly more Machiavellianism and less narcissism than both
informant-reports and meta-perceptions. The relative convergence between meta
perceptions and informant-reports was moderate, and similar to the convergence
between self-reports and informant-reports. Multiple regression analyses in which
self-reports and meta-perceptions predicted informant-reports identified several
significant differences, with meta-perceptions more frequently emerging as a
stronger predictor of informant-reports. These findings suggest that while self
reports and meta-perceptions are closely related, the latter perspective provides
some incremental validity with regard to the constructs that comprise the Dark
Triad. (PsycINFO Database Record
PMID- 27505191
TI - Changing perceptions and efficacy of generic medicines: An intervention study.
AB - OBJECTIVE: Generic medicines provide a safe and economical medical treatment and
are used routinely throughout the world. However, a significant proportion of
individuals view generic medicines as less safe, less effective and of lower
quality compared with their equivalent branded medicines. This study aimed to
investigate the effect of an educational intervention on improving perceptions
and perceived efficacy of generic medicines. METHOD: Seventy participants who
experienced frequent tension headaches were randomized to receive an educational
video about generic medicines or a control video. Participants then alternatively
took branded and generic ibuprofen to treat their next two consecutive headaches.
Changes in perceptions of generic medicines, pain relief and side effects were
measured. RESULTS: The intervention was effective in modifying and improving
perceptions of generic medicines in the areas of understanding (p < .05),
preference for a generic medicine to treat a serious illness (p < .05), and
overall preference for generic medicines (p < .01). However, contrary to
predictions, participants in the intervention group reported significantly less
pain relief (p = .03) and more symptoms (p = .04) after taking generic ibuprofen
compared with branded ibuprofen. CONCLUSION: This study identified that an
educational intervention is effective in modifying and improving perceptions of
generic medicines but produced paradoxical effects on drug efficacy and side
effects. These findings suggest that complex mechanisms are involved in the
relationship between perceptions and drug efficacy and contradict the assumption
that improving attitudes toward generic medicines will have a flow-on effect to
improving health outcomes. (PsycINFO Database Record
PMID- 27505192
TI - Environmental and psychosocial correlates of objectively measured physical
activity among older adults.
AB - OBJECTIVE: Neighborhood environments can support or hinder physical activity
especially as health declines with age. This study puts psychological theories of
health behavior change in context with built environment research to better
understand the interplay of environmental and psychosocial characteristics
impacting older adults' sedentary behavior and physical activity. METHOD: The
Active Streets, Active People study recruited 193 older adults living in a highly
walkable neighborhood in Vancouver, British Columbia, Canada. Participants
completed questionnaires on attitudes toward walking, behavioral control for
walking, and perceived built environment variables. To assess behavior,
participants wore an ActiGraph GT3X + accelerometer for 7 consecutive days.
Regression-based path analysis was conducted to examine whether the link between
the perceived environment and behavior is mediated by psychosocial variables.
RESULTS: In total, 174 participants had valid accelerometry data (Mage = 70.3, SD
= 7.2) and demonstrated a daily average of 525.7 min of sedentary behavior (SD =
65.1) as well as high levels of total physical activity (M = 254.3, SD = 65.1
min/day). Mediation analysis revealed that perceived street connectivity and
diversity of land use were negatively related to sedentary behavior, but only
indirectly through behavioral control. Similarly, effects of street connectivity
and diversity of land use on physical activity were mediated by behavioral
control. CONCLUSIONS: Results highlighted that the perceived built environment is
important for physical activity and sedentary behavior, largely because these
environmental perceptions are positively linked to older adults' confidence in
walking. By integrating environmental and psychosocial correlates of preventive
health behaviors within a theoretical structure, the psychosocial mechanisms
through which the environment affects activity can be better understood.
(PsycINFO Database Record
PMID- 27505193
TI - Viral challenge reveals further evidence of skin-deep resilience in African
Americans from disadvantaged backgrounds.
AB - OBJECTIVE: Studies have revealed a phenomenon called skin-deep resilience, which
develops in upwardly mobile African American youth. They perform well in school,
maintain good mental health, and avoid legal problems. Despite outward
indications of success, they also show evidence of worse health in biomarker
studies. Here we extend this research, asking whether it manifests in
differential susceptibility to upper respiratory infection, and if it emerges in
European Americans as well. METHODS: The sample included 514 adults in good
health, as judged by physician examination and laboratory testing. Participants
completed questionnaires about lifecourse socioeconomic conditions,
conscientiousness, psychosocial adjustment, and lifestyle factors. They were
subsequently inoculated with a rhinovirus that causes upper respiratory
infection, and monitored in quarantine for 5 days the development of illness.
RESULTS: Consistent with past work, African Americans from disadvantaged
backgrounds displayed indications of skin-deep resilience. To the extent these
participants were high in conscientiousness, they fared better across multiple
domains of psychosocial functioning, as reflected in educational attainment,
symptoms of depression, and close relationship quality (p values = .01-.04). But
analyses of these participants' susceptibility to infection revealed the opposite
pattern; higher conscientiousness was associated with a greater likelihood of
becoming ill following inoculation (p value = .03). In European Americans, there
was no evidence of skin-deep resilience; conscientiousness was associated with
better psychosocial outcomes, but not infection risk. CONCLUSIONS: These
observations suggest that resilience may be a double-edged sword for African
Americans from disadvantaged backgrounds. The same characteristics associated
with academic success and psychological adjustment forecast increased
vulnerability to health problems. (PsycINFO Database Record
PMID- 27505195
TI - Implicit processes in health psychology: Diversity and promise.
AB - Implicit processes refer to cognitive, affective, and motivational processes that
influence health decisions and behavior without the person intending that
influence. This special issue aims to increase appreciation of the diverse and
promising research on implicit processes in health psychology, and to promote
discussion about how this research improves understanding of health behavior
change and can be harnessed to meet public health mandates. The articles included
in the special issue showcase this diversity and promise, and present not only
new findings, but also new theories, new measures, and state-of-the- art
summaries of progress. The research demonstrates the added value of considering
implicit processes for understanding health behaviors, their interactions with
explicit processes and neural mechanisms, as well as the benefits of targeting
implicit processes in health behavior interventions. At the same time, however,
the papers in this special issue also point to potential boundary conditions, the
importance of good measures and appropriate tests of implicit processes, and the
challenges involved in assessing implicit processes' causal role in determining
health behaviors. (PsycINFO Database Record
PMID- 27505194
TI - Emotion dysregulation and loss-of-control eating in children and adolescents.
AB - OBJECTIVE: To examine the associations among self-reported loss-of-control (LOC)
eating, emotion dysregulation, body mass, and objective energy intake among
youth. Emotion dysregulation may be 1 individual factor that promotes excess
energy intake and increases in body mass among youth with LOC eating. METHOD:
Children and adolescents (N = 230; 8 to 17 years) enrolled in a nonintervention
study completed a structured interview to determine the presence or absence of
self-reported LOC eating. Children's emotion dysregulation was assessed via
parent-report with the Child Behavior Checklist. Youth also completed 2 test
meals to capture "binge" and "normal" eating. Body composition was examined using
air displacement plethysmography. RESULTS: After controlling for relevant
covariates, youth with self-reported LOC eating had higher parent-reported
emotion dysregulation than those without LOC. Parent-reported emotion
dysregulation was also associated with greater observed energy intake (after
accounting for body mass), as well as higher fat mass. Emotion dysregulation also
moderated associations between LOC status/gender and body mass variables; among
youth with self-reported LOC eating and girls, those with high parent-described
emotion dysregulation (vs. low) had significantly higher fat mass and BMIz.
CONCLUSIONS: Data from the current study suggest that emotion dysregulation may
play a role in energy intake and obesity, particularly among youth with self
reported LOC eating and girls. Additional studies are needed to identify the
prospective mechanisms linking poor emotion regulation and LOC eating. These
mechanisms, in turn, may inform future interventions targeting excess energy
intake and obesity in pediatric samples. (PsycINFO Database Record
PMID- 27505196
TI - The role of attentional bias in obesity and addiction.
AB - OBJECTIVES: The purpose of this article is to critically evaluate the following
claims derived from contemporary theoretical models of attentional bias (AB) for
food- and drug-related stimuli: (a) AB is a characteristic feature of obesity and
addiction, (b) AB predicts future behavior, (c) AB exerts a causal influence on
consummatory behavior, and (d) AB reflects appetitive motivational processes.
METHOD: A focused discussion of the relevant literature is presented. RESULTS:
The available evidence reveals inconsistencies with the aforementioned claims.
Specifically, AB is not consistently associated with individual differences in
body weight or drug use, AB does not consistently predict or influence distal
consummatory behavior, and AB may be influenced by both appetitive and aversive
motivational processes. These insights are synthesized into a theoretical account
that claims that AB for food- and drug-related stimuli arises from momentary
changes in evaluations of those stimuli that can be either positive (when the
incentive value of the food or drug is high), negative (when individuals have a
goal to change their behavior, and those stimuli are perceived as aversive), or
both (when individuals experience motivational conflict, or ambivalence).
CONCLUSIONS: The proposed theoretical synthesis may account for the contributions
of appetitive and aversive motivational processes involved in self-regulatory
conflicts to AB, and it yields testable predictions about the conditions under
which AB should predict and have a causal influence on future consummatory
behavior. This has implications for the prediction and modification of unhealthy
behaviors and associated disorders. (PsycINFO Database Record
PMID- 27505197
TI - Using fuzzy-trace theory to understand and improve health judgments, decisions,
and behaviors: A literature review.
AB - OBJECTIVE: Fuzzy-trace theory is a dual-process model of memory, reasoning,
judgment, and decision making that contrasts with traditional expectancy-value
approaches. We review the literature applying fuzzy-trace theory to health with 3
aims: evaluating whether the theory's basic distinctions have been validated
empirically in the domain of health; determining whether these distinctions are
useful in assessing, explaining, and predicting health-related psychological
processes; and determining whether the theory can be used to improve health
judgments, decisions, or behaviors, especially compared to other approaches.
METHOD: We conducted a literature review using PubMed, PsycINFO, and Web of
Science to identify empirical peer-reviewed papers that applied fuzzy-trace
theory, or central constructs of the theory, to investigate health judgments,
decisions, or behaviors. RESULTS: Seventy nine studies (updated total is 94
studies; see Supplemental materials) were identified, over half published since
2012, spanning a wide variety of conditions and populations. Study findings
supported the prediction that verbatim and gist representations are distinct
constructs that can be retrieved independently using different cues. Although
gist-based reasoning was usually associated with improved judgment and decision
making, 4 sources of bias that can impair gist reasoning were identified.
Finally, promising findings were reported from intervention studies that used
fuzzy-trace theory to improve decision making and decrease unhealthy risk taking.
CONCLUSIONS: Despite large gaps in the literature, most studies supported all 3
aims. By focusing on basic psychological processes that underlie judgment and
decision making, fuzzy-trace theory provides insights into how individuals make
decisions involving health risks and suggests innovative intervention approaches
to improve health outcomes. (PsycINFO Database Record
PMID- 27505198
TI - Techniques for modifying impulsive processes associated with unhealthy eating: A
systematic review.
AB - OBJECTIVE: This systematic review aimed to (a) identify and categorize techniques
used to modify or manage impulsive processes associated with unhealthy eating
behavior, (b) describe the mechanisms targeted by such techniques, and (c)
summarize available evidence on the effectiveness of these techniques. METHOD:
Searches of 5 bibliographic databases identified studies, published in English
since 1993, that evaluated at least 1 technique to modify impulsive processes
affecting eating in adults. Data were systematically extracted on study
characteristics, population, study quality, intervention techniques, proposed
mechanisms of action, and outcomes. Effectiveness evidence was systematically
collated and described without meta-analysis. RESULTS: Ninety-two studies
evaluated 17 distinct impulse management techniques. They were categorized
according to whether they aimed to (a) modify the strength of impulses or (b)
engage the reflective system or other resources in identifying, suppressing, or
otherwise managing impulses. Although higher quality evidence is needed to draw
definitive conclusions, promising changes in unhealthy food consumption and food
cravings were observed for visuospatial loading, physical activity, and if-then
planning, typically for up to 1-day follow-up. CONCLUSIONS: A wide range of
techniques have been evaluated and some show promise for use in weight management
interventions. However, larger-scale, more methodologically robust, community
based studies with longer follow-up times are needed to establish whether such
techniques can have a long-term impact on eating patterns. (PsycINFO Database
Record
PMID- 27505199
TI - Macro-level implicit HIV prejudice and the health of community residents with
HIV.
AB - OBJECTIVES: This study examined how community levels of implicit HIV prejudice
are associated with the psychological and physical well-being of people with HIV
living in those same communities. It also examined whether community motivation
to control prejudice and/or explicit HIV prejudice moderates the relationship of
implicit prejudice and well-being. METHOD: Participants were 206 people with HIV
living in 42 different communities in New England who completed measures that
assessed psychological distress, thriving, and physical well-being. Telephone
surveys of 347 residents of these same communities (selected via random digit
dialing) were used to assess community explicit HIV prejudice and motivation to
control HIV prejudice. These community residents then completed an online measure
of implicit prejudice toward people with HIV, the Implicit Association Test (IAT;
Greenwald, McGhee, & Schwartz, 1998). RESULTS: Multilevel analyses showed that
higher community implicit HIV prejudice was associated with greater psychological
distress among residents with HIV living in that community. The physical well
being of participants with HIV was negatively related to community implicit HIV
prejudice in communities in which residents were unmotivated to control HIV
prejudice or had high levels of explicit HIV prejudice. CONCLUSIONS: These
findings indicate that implicit prejudice of residents of real-world communities
may create an environment that may impair the well-being of stigmatized people.
Implicit prejudice can therefore be considered an element of macro-level or
structural stigma. The discussion considered the possible role of implicit HIV
prejudice on a community's social capital as a pathway by which it compromises
the well-being of residents with HIV. (PsycINFO Database Record
PMID- 27505200
TI - Automatic attitudes and health information avoidance.
AB - OBJECTIVE: Early detection of disease is often crucially important for positive
health outcomes, yet people sometimes decline opportunities for early detection
(e.g., opting not to screen). Although some health-information avoidance reflects
a deliberative decision, we propose that information avoidance can also reflect
an automatic, nondeliberative reaction. In the present research, we investigated
whether people's automatic attitude toward learning health information predicted
their avoidance of risk feedback. METHOD: In 3 studies, we gave adults the
opportunity to learn their risk for a fictitious disease (Study 1), melanoma skin
cancer (Study 2), or heart disease (Study 3), and examined whether they opted to
learn their risk. The primary predictors were participants' attitudes about
learning health information measured using a traditional (controlled) self-report
instrument and using speeded (automatic) self-report measure. In addition, we
prompted participants in Study 3 to contemplate their motives for seeking or
avoiding information prior to making their decision. RESULTS: Across the 3
studies, self-reported (controlled) and implicitly measured (automatic) attitudes
about learning health information independently predicted avoidance of the risk
feedback, suggesting that automatic attitudes explain unique variance in the
decision to avoid health information. In Study 3, prompting participants to
contemplate their reasons for seeking versus avoiding health information reduced
information avoidance. Surprisingly, it did so by inducing reliance on automatic,
rather than controlled, attitudes. CONCLUSION: The data suggests that automatic
processes play an important role in predicting health information avoidance and
suggest that interventionists aiming to increase information seeking might
fruitfully target automatic processes. (PsycINFO Database Record
PMID- 27505201
TI - "Are we overestimating the prevalence of depression in chronic illness using
questionnaires? Meta-analytic evidence in obstructive sleep apnoea": Correction
to Nanthakumar et al. (2016).
AB - Reports an error in "Are we overestimating the prevalence of depression in
chronic illness using questionnaires? Meta-analytic evidence in obstructive sleep
apnoea" by Shenooka Nanthakumar, Romola S. Bucks and Timothy C. Skinner (Health
Psychology, 2016[May], Vol 35[5], 423-432). In the article, "Cognitive items"
should read "Cognition items" in column 1, line 7 of Table 2. (The following
abstract of the original article appeared in record 2015-49649-001.)
INTRODUCTION: Depression is common in chronic illness, albeit prevalence can be
highly variable. This variability may be a function of symptom overlap between
depression and chronic illness. Using Obstructive Sleep Apnoea (OSA) as an
exemplar, this meta-analysis explored whether the proportion of overlapping
symptoms between OSA and depression, within different depression questionnaires,
moderates prevalence estimates. METHODS: A systematic search identified 13
studies meeting eligibility criteria. RESULTS: Based on depression
questionnaires, the prevalence of depression in OSA ranged from 8% to 68%,
reflecting marked heterogeneity. Prevalence estimates based on questionnaires
with greater symptom overlap between OSA and depression were higher, whereas
questionnaires with a higher proportion of anhedonia symptoms were associated
with lower prevalence estimates. DISCUSSION: Overall, these data suggest that
when using depression questionnaires to assess the prevalence of depression in
OSA, questionnaires that have a lower proportion of symptom overlap between OSA
and depression, as well as a higher proportion of anhedonia symptoms, reduce the
likelihood of overestimating the prevalence of depression in OSA. This study has
implications for other chronic illnesses with symptom overlap with depression,
for example diabetes, chronic kidney disease, or heart disease, as well as
suggesting that depression questionnaires are not equally appropriate for
assessing depression symptomatology in chronic illness populations.
PMID- 27505202
TI - Self-reported and automatic cognitions are associated with exercise behavior in
cancer survivors.
AB - OBJECTIVE: Physical activity is beneficial for cancer survivors, but exercise
participation is low in this population. It is therefore important to understand
the psychological factors underlying exercise uptake so that more effective
interventions can be developed. Social-cognitive theory constructs such as
outcome expectancies predict exercise behavior, but self-report measures have
several limitations. We examined the associations between implicit (automatic)
cognitions and exercise behavior and self-efficacy in endometrial cancer
survivors. METHOD: This was a longitudinal study to examine predictors of
exercise behavior in female endometrial cancer survivors who all received an
exercise intervention. Participants (N = 100, mean age of 57.0) completed
questionnaires to assess self-report exercise-related measures (outcome
expectancy and attitudes about and identification with exercise) and reaction
time (RT) tasks to assess implicit exercise cognitions (expectancy accessibility,
implicit attitudes about exercise, and implicit self-identification with
exercise) at baseline and at 2, 4, and 6 months at follow-up. Exercise behavior
was measured using accelerometers and self-report. Data were analyzed using
linear mixed models. RESULTS: Expectancy accessibility was associated with
exercise duration independent of the corresponding self-report measure. Exercise
implicit attitudes and self-identification were prospectively associated with
exercise self-efficacy only after adjustment for the corresponding self-report
measures and baseline self-efficacy. Self-report measures were also associated
with study outcomes. CONCLUSIONS: Both self-reported cognitions and implicit
cognitions may be useful to identify individuals at risk of failing to exercise.
Individuals so identified might be provided with a different or more intensive
intervention. The data also suggest cognitive targets for intervention. (PsycINFO
Database Record
PMID- 27505203
TI - Implicit attitudes predict drinking onset in adolescents: Shaping by social
norms.
AB - OBJECTIVE: Implicit attitudes toward alcohol predict drinking among adults and
adolescents. If implicit attitudes reflected associations learned through direct
experience with drinking, then they would likely only predict drinking among
individuals who have previously consumed alcohol. In contrast, if implicit
attitudes reflected indirect experience through social messages, they might also
then predict future drinking, even among individuals with no drinking experience.
In this study, we tested whether implicit attitudes would predict initiation of
drinking for the first time, and whether parents' and friends' norms toward
alcohol would influence the development of implicit attitudes. METHOD: For this
study, we followed 868 adolescents between the ages of 12 and 15 years for 3
years. Implicit attitudes were measured using the affect misattribution procedure
(Payne, Cheng, Govorun, & Stewart, 2005; Payne, Govorun, & Arbuckle, 2008).
Explicit intentions to drink and the frequency of drinking and binge drinking
were measured at each of 3 annual waves. RESULTS: Implicit attitudes toward
alcohol predicted future drinking behavior 1 year later, and effects were similar
for adolescents who had previously tried alcohol and for those who had not. To
understand what factors might shape implicit attitudes among participants without
drinking experience, we examined the role of parental norms and friends' norms
toward drinking. Parental approval of drinking predicted the development of more
positive implicit attitudes, which in turn predicted later drinking. CONCLUSION:
Implicit attitudes toward alcohol can develop in advance of direct experience
drinking alcohol. Results have implications for the implicit processes
underpinning adolescent drinking, and the processes by which implicit
associations are learned. (PsycINFO Database Record
PMID- 27505204
TI - Perceived controllability of condom use shifts reliance on implicit versus
explicit affect.
AB - OBJECTIVES: This study integrated the framework of the behavioral affective
associations model with dual process theories to investigate whether feelings
about condoms operate at both implicit and explicit levels to influence condom
use. We then tested whether 2 factors related to the perceived controllability of
condom use (perceived behavioral control and past experience losing control in
the heat of the moment) moderated the reliance on implicit versus explicit
affect. METHOD: Sexually active young adults (N = 54) completed measures of
implicit and explicit affect surrounding condoms, perceived behavioral control,
and whether they attributed their prior unprotected sex to getting lost in the
heat of the moment. They then completed 30 daily reports of their sexual activity
and condom use. Multiple moderation analysis using generalized estimating
equation (GEE) models tested the relative influence of implicit and explicit
affect on condom use at varying levels of perceived controllability. RESULTS:
Both perceived behavioral control and past unprotected sex because of getting
lost in the heat of the moment moderated the effects of both implicit and
explicit affect on behavior, ps < .05. Only implicit affect predicted condom use
among participants who had gotten lost in the heat of the moment and who had low
perceived behavioral control. Only explicit affect predicted condom use among
participants without a history of getting lost in the heat of the moment and who
had high perceived behavioral control. CONCLUSION: Feelings about condoms
predicted condom use at either an implicit or explicit level, depending on
perceived controllability, suggesting this is an important moderator of whether
implicit processes drive condom use. (PsycINFO Database Record
PMID- 27505205
TI - Pairing images of unhealthy and healthy foods with images of negative and
positive health consequences: Impact on attitudes and food choice.
AB - OBJECTIVE: To examine the impact of presenting images of foods paired with images
of positive and negative health consequences of their consumption on food choice
and attitudes. METHOD: Participants (N = 711) were randomly allocated in a 2 * 3
factorial design (Food Type * Affective Valence) to 1 of 6 conditioning
procedures that paired images of either energy-dense snack foods or fruit, with
(a) images of negative health outcomes, (b) images of positive health outcomes,
or (c) a no image control. The primary outcome was food choice assessed
postintervention with a behavioral choice task. Secondary outcomes were implicit
attitudes (assessed pre- and postintervention) and explicit attitudes (assessed
postintervention). RESULTS: Presenting images of negative health outcomes led to
more healthy food choices relative to control and positive image conditions,
irrespective of whether they were paired with images of energy-dense snack foods
or fruit. This relationship was partially mediated by changes in implicit and
explicit attitudes. Images of positive health outcomes did not alter food
choices. CONCLUSIONS: This study replicates and extends previous research showing
that presenting images of negative health consequences increases healthy food
choices. Because effects were elicited by manipulating affective valence
irrespective of paired food type, these results appear more consistent with an
explanation based on priming than on evaluative conditioning. (PsycINFO Database
Record
PMID- 27505206
TI - Generalization of evaluative conditioning toward foods: Increasing sensitivity to
health in eating intentions.
AB - OBJECTIVE: Evaluative conditioning (EC), the pairing of objects (conditioned
stimuli; CS) with positive and negative unconditioned stimuli (US) in order to
induce attitude change, has proven to be a viable method of changing attitudes
toward foods and corresponding eating behaviors. Positively conditioning healthy
foods and negatively conditioning unhealthy foods should result in healthier food
choices. Of interest in the current research is the extent to which EC can
generalize beyond the conditioned foods to entire dimensions underlying food
judgment, such as health and taste. METHOD: The current research included 2 EC
experiments configured in accord with the Implicit Misattribution Model (IMM;
Jones, Fazio, & Olson, 2009). Four healthy CS foods were paired with positive US
and 4 unhealthy CS foods were paired with negative US. Participants then reported
eating intentions for a variety of foods, including non-CS foods. RESULTS:
Experiment 1 demonstrated that conditioning a few exemplar food items increased
sensitivity to health and decreased sensitivity to taste when judging a variety
of additional foods. Experiment 2 replicated the generalization effect with
regard to health sensitivity, but only when a task that preceded the EC procedure
promoted, rather than interfered with, categorization of the CS foods by health.
CONCLUSIONS: This research shows that EC can generalize to an entire dimension
underlying food judgment and that this effect is facilitated by accessibility of
the health dimension at the time of exposure to the EC pairings. (PsycINFO
Database Record
PMID- 27505207
TI - To accurately estimate implicit influences on health behavior, accurately
estimate explicit influences.
AB - OBJECTIVE: This project considered how inattention to left-out variable error and
measurement correspondence in the assessment of explicit measures can result in
upwardly biased estimates of the predictive utility of implicit measures designed
to predict health behaviors. METHOD: A pilot study (n = 96) used a cross
sectional design to predict beer consumption and a main study (n = 132) used a
longitudinal design to predict binge drinking. In each study, a battery of 4
implicit inventories (implicit association test, personalized implicit
association test, evaluative priming, and attribution misattribution paradigm)
and a battery of correspondent explicit measures (based on the Reasoned Action
Model and the Prototype Willingness Model) were administered to college youth.
RESULTS: The Implicit Association Test and evaluative priming measures were not
predictive of alcohol consumption in either study, but the personalized implicit
association test (PIAT) and affective misattribution paradigm (AMP) accounted for
between 5% and 12% in behavioral criteria, when analyzed in isolation or after
explicit measures were statistically controlled following measurement conventions
in this research domain. When implicit measures were folded into a structural
equation model derived from the Reasoned Action and Prototype Willingness Models,
The PIAT was no longer a significant predictor of behavior and the AMP resulted
in a 1%-2% incremental increase in accounted for variance. CONCLUSION: Left-out
variable error and measurement correspondence are core principles that need to be
considered when modeling the relative contributions of implicit and explicit
constructs in the prediction of health behaviors. (PsycINFO Database Record
PMID- 27505208
TI - Implicit stigmatization-related biases in individuals with skin conditions and
their significant others.
AB - OBJECTIVE: Stigmatization is common in people with chronic skin conditions and
may also affect their significant others (SOs). The fast and implicit processing
of stigmatization-related stimuli has received little attention in these
populations; however, such knowledge may offer indications for new treatment
methods. This study aimed to investigate implicit processing of stigmatization
related stimuli in people with skin conditions and their SOs. METHOD: A modified
Stroop task and 2 approach-avoidance tasks were administered to participants with
chronic skin conditions (alopecia: n = 50 and psoriasis: n = 50); their
significant others (alopecia SOs: n = 47 and psoriasis SOs: n = 50); and controls
(n = 50). The aim was to examine attentional and behavioral biases toward disease
related and social threat-related stigmatization stimuli. RESULTS: An attentional
bias to disease-related stimuli was found in participants with alopecia and their
SOs, compared with controls (p < .001). This effect was not found for
participants with psoriasis and their SOs. Increased behavioral avoidance of
disgusted faces was found in participants with psoriasis and their SOs, compared
with controls (p = .047). This effect was not found in participants with alopecia
and their SOs. CONCLUSIONS: These results provide support for the idea that
individuals with skin conditions and their SOs are characterized by a
stigmatization-related stimulus bias regarding implicit cognitive and behavioral
reactions, in comparison to healthy individuals. Furthermore, preliminary results
suggest that these processes may differ across skin conditions, with people with
psoriasis being more affected by social reactions (i.e., disgusted faces) and
people with alopecia by disease-related cues possibly related to internalized
self-stigma. (PsycINFO Database Record
PMID- 27505209
TI - Smokers exhibit biased neural processing of smoking and affective images.
AB - OBJECTIVE: There has been growing interest in the role that implicit processing
of drug cues can play in motivating drug use behavior. However, the extent to
which drug cue processing biases relate to the processing biases exhibited to
other types of evocative stimuli is largely unknown. The goal of the present
study was to determine how the implicit cognitive processing of smoking cues
relates to the processing of affective cues using a novel paradigm. METHOD:
Smokers (n = 50) and nonsmokers (n = 38) completed a picture-viewing task, in
which participants were presented with a series of smoking, pleasant, unpleasant,
and neutral images while engaging in a distractor task designed to direct
controlled resources away from conscious processing of image content.
Electroencephalogram recordings were obtained throughout the task for extraction
of event-related potentials (ERPs). RESULTS: Smokers exhibited differential
processing of smoking cues across 3 different ERP indices compared with
nonsmokers. Comparable effects were found for pleasant cues on 2 of these
indices. Late cognitive processing of smoking and pleasant cues was associated
with nicotine dependence and cigarette use. CONCLUSIONS: Results suggest that
cognitive biases may extend across classes of stimuli among smokers. This raises
important questions about the fundamental meaning of cognitive biases, and
suggests the need to consider generalized cognitive biases in theories of drug
use behavior and interventions based on cognitive bias modification. (PsycINFO
Database Record
PMID- 27505210
TI - A randomized controlled trial of Web-based Attentional Bias Modification to help
smokers quit.
AB - OBJECTIVE: To assess the efficacy of a multiple-sessions Web-based Attentional
Bias Modification (ABM) self-help intervention in 434 smokers who made a quit
attempt. METHOD: Respondents were randomized to receive 6 sessions of ABM- or
placebo-training in a period of 2 weeks. Smoking-related cognitions (e.g., self
efficacy and intention to quit) and cognitive biases (i.e., attentional and
approach bias) for smoking-cues were assessed before training (pretest). Primary
outcome-variable was continued abstinence, 6 months after baseline. Bias
reduction at the posttraining assessment was the secondary outcome. A 2 * 2 mixed
analysis of variance (ANOVA) and logistic regression analyses were conducted
using the whole sample (N = 434) as well as subsamples of light to moderate
smokers (<15 cigarettes, N = 115) and heavy smokers (15 or more cigarettes, N =
319). Conservative analyses (coding drop-outs as smokers) as well as complete
case analyses were conducted. RESULTS: The ABM training had no significant effect
regarding bias reduction and no behavioral effects in the whole sample of
smokers. Subsample analyses revealed a significant positive effect on continued
abstinence in heavy smokers only (complete case analyses: odds ratio [OR] = 3.15;
p = .02; confidence interval [CI] = 1.24-7.99; conservative analyses: OR = 2.49;
p = .02; CI = 1.13-5.48). CONCLUSION: Web-based ABM training is ineffective in
fostering cognitive bias reduction and continued smoking abstinence. However, the
positive effects in heavy smokers-as indicated by exploratory subsample analyses
warrant further research into the potential of multiple sessions ABM training to
foster continued smoking abstinence in heavy smokers who make a quit-attempt.
(PsycINFO Database Record
PMID- 27505212
TI - Attentional effects of self-affirmation in response to graphic antismoking
images.
AB - OBJECTIVE: Self-affirmation has been shown to reduce defensive responding to
threatening information. However, little is known about the cognitive and
attentional processes underlying these effects. In the current eye-movement
study, the authors explored whether self-affirmation affects attention allocation
(i.e., number of fixations) among those for whom a threatening health message is
self-relevant. METHODS: After a self-affirmation manipulation, 47 smokers and 52
nonsmokers viewed a series of cigarette packs displaying high or low threat
smoking-related images accompanied by a brief smoking message containing risk,
coping or neutral textual information. RESULTS: Self-affirmed smokers made more
fixations to the cigarette packs than did nonaffirmed smokers (across both high
and low threat images), whereas self-affirmed nonsmokers made fewer fixations to
the cigarette packs than did nonaffirmed nonsmokers (again across both image
types). The textual information did not moderate responses. CONCLUSIONS: Findings
indicate attention-increasing effects of self-affirmation among those for whom
the information is self-relevant (smokers) and attention-decreasing effects of
self-affirmation among those for whom the information is not self-relevant
(nonsmokers). Such findings are consistent with the calibration model of self
affirmation (Griffin & Harris, 2011) in which self-affirmation increases
sensitivity to the self-relevance of health-risk information. The use of an
implicit measure of visual orienting informs our understanding of the working
mechanisms of self-affirmation when encoding health information, and may also
hold practical implications for the design and delivery of graphic warning
labels. (PsycINFO Database Record
PMID- 27505211
TI - Attentional bias to negative affect moderates negative affect's relationship with
smoking abstinence.
AB - OBJECTIVE: To examine whether initial orienting (IO) and inability to disengage
(ITD) attention from negative affective stimuli moderate the association of
negative affect with smoking abstinence during a quit attempt. METHOD: Data were
from a longitudinal cohort study of smoking cessation (N = 424). A negative
affect modified Stroop task was administered 1 week before and on quit day to
measure IO and ITD. Ecological Momentary Assessments were used to create negative
affect intercepts and linear slopes for the week before quitting and on quit day.
Quit day and long-term abstinence measures were collected. RESULTS: Continuation
ratio logit model analyses found significant interactions for prequit negative
affect slope with prequit ITD, odds ratio (OR) = 0.738 (0.57, 0.96), p = .02, and
for quit day negative affect intercept with quit day ITD, OR = 0.62 (0.41, 950),
p = .03, predicting abstinence. The Prequit Negative Affect Intercept * Prequit
IO interaction predicting quit day abstinence was significant, OR = 1.42 (1.06,
1.90), p = .02, as was the Quit Day Negative Affect Slope * Quit Day IO
interaction predicting long-term abstinence, OR = 1.45 (1.02, 2.08), p = .04.
CONCLUSION: The hypothesis that the association of negative affect with smoking
abstinence would be moderated by ITD was generally supported. Among individuals
with high ITD, negative affect was inversely related to abstinence, but unrelated
to abstinence among individuals with lower levels of ITD. Unexpectedly, among
individuals with low IO, negative affect was inversely related to abstinence, but
unrelated to abstinence among individuals with higher levels of ITD. (PsycINFO
Database Record
PMID- 27505213
TI - When is an image a health claim? A false-recollection method to detect implicit
inferences about products' health benefits.
AB - OBJECTIVE: Images on food and dietary supplement packaging might lead people to
infer (appropriately or inappropriately) certain health benefits of those
products. Research on this issue largely involves direct questions, which could
(a) elicit inferences that would not be made unprompted, and (b) fail to capture
inferences made implicitly. Using a novel memory-based method, in the present
research, we explored whether packaging imagery elicits health inferences without
prompting, and the extent to which these inferences are made implicitly. METHOD:
In 3 experiments, participants saw fictional product packages accompanied by
written claims. Some packages contained an image that implied a health-related
function (e.g., a brain), and some contained no image. Participants studied these
packages and claims, and subsequently their memory for seen and unseen claims
were tested. RESULTS: When a health image was featured on a package, participants
often subsequently recognized health claims that-despite being implied by the
image-were not truly presented. In Experiment 2, these recognition errors
persisted despite an explicit warning against treating the images as informative.
In Experiment 3, these findings were replicated in a large consumer sample from 5
European countries, and with a cued-recall test. CONCLUSION: These findings
confirm that images can act as health claims, by leading people to infer health
benefits without prompting. These inferences appear often to be implicit, and
could therefore be highly pervasive. The data underscore the importance of
regulating imagery on product packaging; memory-based methods represent
innovative ways to measure how leading (or misleading) specific images can be.
(PsycINFO Database Record
PMID- 27505214
TI - "Relational effects on physical activity: A dyadic approach to the theory of
planned behavior": Correction to Howland et al. (2016).
AB - Reports an error in "Relational effects on physical activity: A dyadic approach
to the theory of planned behavior" by Maryhope Howland, Allison K. Farrell,
Jeffry A. Simpson, Alexander J. Rothman, Rachel J. Burns, Jennifer Fillo and Jhon
Wlaschin (Health Psychology, 2016[Jul], Vol 35[7], 733-741). In the article,
NIAAA Grant 5T32-AA07290 provided funding support for manuscript preparation but
was omitted from the author note. (The following abstract of the original article
appeared in record 2016-10019-001.) OBJECTIVE: Despite growing appreciation of
how close relationships affect health outcomes, there remains a need to explicate
the influence romantic partners have on health behavior. In this paper, we
demonstrate how an established model of behavior change-the theory of planned
behavior (TPB)- can be extended from an individual level to a dyadic (couple)
model to test the influence that relationship partners have on a key determinant
of health behavior-behavioral intentions. METHODS: Two hundred romantic couples
(400 individuals) completed TPB measures regarding physical activity for
themselves and their romantic partner as well as a measure of relationship
quality. RESULTS: Above and beyond the individual-level TPB predictors of
behavioral intentions (i.e., attitudes, subjective norms, and perceived
behavioral control), the romantic partner's perceived behavioral control (PBC)
regarding physical activity predicted each individual's behavioral intentions and
moderated the influence of each individual's PBC on his or her own behavioral
intentions. Additionally, the romantic partner's perceptions of each individual's
TPB measures predicted each individual's behavioral intentions to be physically
active. Quality of the relationship also moderated some partner influences on
individuals' intentions. CONCLUSIONS: This paper provides a roadmap for
integrating a dyadic framework into individual-level models of behavior change.
The findings suggest that data from both partners and relationship quality are
important to consider when trying to understand and change health-related
behavior such as physical activity. The results broaden the potential
applications of the TPB as well as our understanding of how romantic partners
might influence important health-related practices.
PMID- 27505216
TI - Targeting implicit approach reactions to snack food in children: Effects on
intake.
AB - OBJECTIVE: Implicit approach reactions to energy-dense snack food can facilitate
unhealthy eating in children. Therefore, an experiment was conducted to test
whether modifying implicit reactions to snack food by means of a go/no-go task
can reduce consumption of this food. The effectiveness of this intervention on
actual snack intake after exposure to a food or a control advertisement was
tested. METHOD: Children (133; age range = 7-10 years) played an advergame
promoting either energy-dense food or nonfood products. Subsequently, children
conducted either a go/no-go food task in which the advertised food was
consistently associated with no-go cues, or a go/no-go control task in which
colored circles were consistently associated with no-go cues. Afterward, they
could eat the advertised food and a new food. Candy intake was weighed and
caloric intake was determined. RESULTS: Results show that children who performed
the go/no-go food task consumed significantly and considerably fewer calories
(34%) than the children who carried out the control task. No main effect of type
of advertisement was found. Furthermore, the effect of the go/no-go food task was
similar after each type of advertisement, similar for advertised and new foods,
and was significant for both girls and boys. CONCLUSION: Targeting implicit
reactions to high-energy snacks proved effective in decreasing intake of snacks
in children. Furthermore, the previously reported stimulating effect of food
promoting advergames on intake may disappear when a short cognitive task is
presented directly after the game. Future work should evaluate the clinical
implications of these findings. (PsycINFO Database Record
PMID- 27505215
TI - Implicit alcohol associations, especially drinking identity, predict drinking
over time.
AB - OBJECTIVE: There is considerable excitement about implicit alcohol associations
(IAAs) as predictors of college-student hazardous drinking; however, few studies
have investigated IAAs prospectively, included multiple assessments, or
controlled for previous drinking. Doing so is essential for showing the utility
of these associations as predictors, and ultimately, targets for screening or
intervention. Therefore, 3 IAAs (i.e., drinking identity, alcohol approach, and
alcohol excitement) were evaluated as prospective predictors of drinking in 1st-
and 2nd-year undergraduates in the United States. METHOD: A sample of 506
undergraduates completed 8 online assessments of IAAs, explicit measures of the
IAA constructs, and hazardous drinking (i.e., consumption, problems, and risk of
alcohol-use disorders) every 3 months over a 21-month period. Retention rates,
ordered by follow-up time points, were 90%, 76%, 76%, 77%, 72%, 67%, and 66%,
respectively. Half of the participants were nondrinkers at baseline; 21% were
above clinical cutoffs for hazardous drinking. RESULTS: Drinking-identity and
alcohol-excitement associations predicted future alcohol consumption and problems
after controlling for previous drinking and explicit measures; drinking identity
also predicted future risk of alcohol-use disorder. Relative to the other IAAs,
drinking identity predicted alcohol consumption for the longest duration (i.e.,
21 months). Alcohol-approach associations rarely predicted variance in drinking.
CONCLUSION: IAAs vary in their utility as prospective predictors of college
student hazardous drinking. Drinking identity and, to a lesser extent, alcohol
excitement, emerged as robust prospective predictors of hazardous drinking.
Intervention and screening efforts could likely benefit from targeting those
associations. (PsycINFO Database Record
PMID- 27505217
TI - Snack intake is reduced using an implicit, high-level construal cue.
AB - OBJECTIVES: Priming a high level construal has been shown to enhance self-control
and reduce preference for indulgent food. Subtle visual cues have been shown to
enhance the effects of a priming procedure. The current study therefore examined
the combined impact of construal level and a visual cue reminder on the
consumption of energy-dense snacks. METHOD: A student and community-based adult
sample with a wide age and body mass index (BMI) range (N = 176) were randomly
assigned to a high or low construal condition in which a novel symbol was
embedded. Afterward participants completed a taste test of ad libitum snack foods
in the presence or absence of the symbol. RESULTS: The high (vs. the low)
construal level prime successfully generated more abstract responses (p < .0001)
and reduced intake when the cue-reminder was present (p = .02) but not when it
was absent (p = .40). CONCLUSIONS: Priming high construal level thinking reduces
consumption of high energy dense snacks in the presence of a visual cue-reminder.
This may be a practical technique for reducing overeating and has the potential
to be extended to other unhealthy behaviors. (PsycINFO Database Record
PMID- 27505218
TI - The Impact of Integrated Psychological Services in a Safety Net Primary Care
Clinic on Medical Utilization.
AB - OBJECTIVE: The integration of psychological and behavioral health services into
safety net primary care clinics has been viewed as a step toward reducing
disparities in mental health treatment and addressing behavioral factors in
chronic diseases. Though it is posited that integrated behavioral health (IBH)
reduces preventable medical costs, this premise has yet to be tested in a safety
net primary care clinic. METHOD: Retrospective pre- and posttreatment analysis
with quasi-experimental control group was constructed using propensity score
matching. Participants included 1,440 adult patients at a safety net primary care
clinic, 720 of whom received IBH services, and 720 of whom received medical
treatment only. RESULTS: Analysis showed that rates of preventable inpatient
utilization decreased significantly among IBH-treated patients compared to no
change among control patients. CONCLUSION: IBH was associated with decreased
rates of preventable inpatient visits. IBH may present opportunities to deliver
improved holistic patient care while reducing unnecessary inpatient medical
utilization.
PMID- 27505219
TI - Supramolecular Photochirogenesis with a Higher-Order Complex: Highly Accelerated
Exclusively Head-to-Head Photocyclodimerization of 2-Anthracenecarboxylic Acid
via 2:2 Complexation with Prolinol.
AB - An unprecedented 2:2 complex was shown to intervene in the enantiodifferentiating
photocyclodimerization of 2-anthracenecarboxylic acid (A) mediated by a hydrogen
bonding template l-prolinol (P) to accelerate the formation of chiral anti-head
to-head and achiral syn-head-to-head cyclodimers in >99% combined yield with
enhanced enantioselectivities of up to 72% ee for the former. The supramolecular
complexation and photochirogenic behaviors, as well as the plausible structures,
of intervening Am.Pn complexes (m, n = 1 or 2) were elucidated by combined
theoretical and experimental spectroscopic, photophysical, and photochemical
studies. Furthermore, the photochemical chiral amplification was achieved for the
first time by utilizing the preferential 2:2 complexation of A with homochiral P
to give normalized product enantioselectivities higher than those of the template
used. The present strategy based on the higher-order hydrogen-bonding motif,
which is potentially applicable to a variety of carboxylic acids and beta
aminoalcohols, is not only conceptually new and expandable to other
(photo)chirogenic and sensing systems but also may serve as a versatile tool for
achieving photochemical asymmetric amplification and constructing chiral
functional supramolecular architectures.
PMID- 27505220
TI - Comparison of the Motor Performance and Vestibular Function in Infants with a
Congenital Cytomegalovirus Infection or a Connexin 26 Mutation: A Preliminary
Study.
AB - OBJECTIVES: Hearing-impaired children are at risk for vestibular damage and
delayed motor development. Two major causes of congenital hearing loss are
cytomegalovirus (CMV) infection and connexin (Cx) 26 mutations. Comparison of the
motor performance and vestibular function between these specific groups is still
underexplored. The objective of this study was to investigate the impact of
congenital (c)CMV and Cx26 on the motor performance and vestibular function in 6
months old infants. DESIGN: Forty children (mean age 6.7 months; range 4.8 to 8.9
months) participated in this cross-sectional design and were recruited from the
Flemish CMV registry. They were divided into five age-matched groups: normal
hearing control, asymptomatic cCMV, normal-hearing symptomatic cCMV, hearing
impaired symptomatic cCMV, and hearing-impaired Cx26. Children were examined with
the Peabody Developmental Motor Scales-2 and cervical vestibular-evoked myogenic
potential (cVEMP) test. RESULTS: Symptomatic hearing-impaired cCMV children
demonstrated a significantly lower gross motor performance compared with the
control group (p = 0.005), the asymptomatic cCMV group (p = 0.034), and the Cx26
group (0.016). In this symptomatic hearing-impaired cCMV group, 4 out of 8
children had absent cVEMP responses that were related to the weakest gross motor
performance. The Cx26 children showed no significant delay in motor development
compared with the control children and none of these children had absent cVEMP
responses. CONCLUSIONS: The weakest gross motor performance was found in
symptomatic hearing-impaired cCMV-infected children with absent cVEMP responses.
These results suggest that abnormal saccular responses are a major factor for
this delayed motor development, although more work is needed including
comprehensive vestibular function testing to verify this.
PMID- 27505221
TI - Infant Cortical Auditory Evoked Potentials to Lateralized Noise Shifts Produced
by Changes in Interaural Time Difference.
AB - OBJECTIVES: Newborns reliably orient to sound location soon after birth; by age 1
month this orienting disappears until after age 4 months. It has been suggested
that orienting by the newborn reflects subcortical-mediated reflexes, which are
suppressed by age 1 month; reappearance of orienting then occurs after age 4
months with maturation of cortical mechanisms of sound localization. In the
present study, we assess auditory lateralization in young infants (and adults) by
recording slow cortical auditory evoked potentials to lateralization shifts in
dichotic noise produced by changes in interaural time difference (ITD). DESIGN:
Fifteen normal infants aged under 4 months (mean = 10.7 weeks) had cortical
auditory evoked potentials assessed in response to (1) diotic "onset" noise
bursts (0 msec ITD) and (2) shifts in continuous lateralized noise (75 dB SPL)
produced by ITD shifts of 0.5, 0.8, 1, 2, 4, and 8 msec. Shifts alternated
between ears occurred every 2 sec. Stimuli were presented using insert earphones;
infants slept during recordings. For comparison, similar recordings were obtained
in 11 normal-hearing, awake, adults. Additionally, "control" recordings to the
ITD-shift stimuli presented to only one ear were obtained in the adults. RESULTS:
Similar to previous research, adults showed clear N1-P2 responses to the
lateralization shifts (ITD 0.5 to 2.0 msec). Responses decreased for longer ITD
shifts, with no adult responses to the 8-msec ITD shift. N1 latencies to ITD
shift stimuli were 28 to 34 msec longer than to the onset stimuli. No responses
were seen in the control conditions when ITD-shift stimuli were presented to only
one ear (confirming the binaural nature of the ITD-shift responses). All infants
showed P2 responses to one or more of the ITD-shift stimuli up to +/-1 msec;
compared with adults, infants showed larger amplitude decreases and fewer
responses to longer ITD-shift stimuli. As was seen with the adult responses,
infant response (P2) latencies to ITD shifts were longer compared with their
responses to the onset stimuli; however, these increases, 32 to 78 msec, were
significantly longer than those seen in the adults. CONCLUSIONS: Young infants
(even as young as 5 weeks) show clear evidence of auditory cortical responsivity
to lateralization shifts produced by changes in the ITD of continuous noise,
indicating that they have the capacity to process binaural ITD timing cues well
before the age of 4 months. Further research is required to determine whether the
larger latency increase in infants for ITD-shift stimuli (relative to the onset
stimuli) and the greater effect of longer ITD shifts on response presence and
amplitude in infants reflects immaturity of lateralization processing and/or
reduced responses recorded during sleep. Slow cortical auditory evoked potentials
elicited to lateralization shifts in dichotic noise provide a method to
investigate binaural hearing processes in young children with normal or impaired
hearing.
PMID- 27505222
TI - The role of dimension relevance in features' access to response-selection
mechanisms.
AB - It is widely agreed that attending to a stimulus entails that all its features
are processed. However, whether all these features are granted access to response
selection mechanisms remains a debated issue. Some authors suggest that all the
features of the attended object affect response selection, irrespective of their
relevance to the task at hand, whereas others claim that only its currently
relevant features do. Yet others suggest that irrelevant features of an attended
object affect response selection only if this object is the target, that is, only
if it is selected for action. The results from 3 experiments show that responses
associated with an attended object's irrelevant dimension interfered with
response selection even when this object was not selected for action, but to a
lesser extent than the responses associated with its relevant dimension. Our
findings also show that interference from the irrelevant dimension can be masked
when the response codes associated with the relevant and irrelevant dimensions
compete. We suggest a parsimonious account of the findings from the extant
literature that obviates the need to postulate a qualitative distinction between
attention and selection for action. (PsycINFO Database Record
PMID- 27505223
TI - Parallel streams versus integrated timing in multilimb pattern generation: A test
of Korte's Third Law.
AB - Skilled drummers performed a 4:3:2 polyrhythm with 2 hands and 1 foot. For each
pair of limbs patterns of temporal covariation were used to infer relatively
independent parallel streams versus integrated timing relationships. Parallel
timing was more prevalent between hand and foot than between the 2 hands, and
parallel timing generally increased with tapping rate. Different combinations of
integrated and parallel timing were found among the 3 limbs. A second experiment
used a wider range of tapping rates and explored 3:2 tapping with 2 hands, 2
feet, or hand and foot. The latter 2 limb pairs resulted in greater prevalence of
parallel timing. These results can be interpreted in terms of a Gestalt principle
of grouping known as Korte's Third Law, which can be extended from the perceptual
domain to the perceptual-motor domain. This principle indicates that perceived
velocity is a key factor in determining whether a sequence of events is
represented as a single integrated pattern or as multiple parallel patterns. The
present results put disparate previous findings on bimanual polyrhythmic tapping
and rhythmic aspects of the golf swing under a common theoretical perspective.
(PsycINFO Database Record
PMID- 27505224
TI - Auditory stimuli automatically grab attention: Evidence from eye tracking and
attentional manipulations.
AB - Simultaneously presenting auditory and visual stimuli can hinder performance for
one modality while the other dominates. For approximately 40 years, research with
adults has primarily indicated visual dominance, while recent research with
infants and young children has revealed auditory dominance. The current study
further investigates modality dominance with adults, finding evidence for both
auditory and visual dominance across 3 experiments. Using a simple discrimination
task, Experiment 1 revealed that cross-modal presentation attenuated
discrimination of auditory input, while at the same time, also slowed down visual
processing. Even when participants were instructed to only pay attention to the
visual stimuli, both spoken nonsense words and nonlinguistic sounds slowed down
visual processing (Experiment 2). Experiment 3 used a similar discrimination task
while utilizing an eye tracker to examine how auditory input affects visual
fixations. Cross-modal presentation attenuated auditory discrimination; however,
it also slowed down visual response times. In addition, adults also made longer
fixations and were slower to make their first fixation when images were paired
with sounds. The latter finding is novel and consistent with a proposed mechanism
of auditory dominance: auditory stimuli automatically engage attention and
attenuate or delay visual processing. (PsycINFO Database Record
PMID- 27505225
TI - Assessing the functional role of motor response during the integration process.
AB - The aim of this study was to provide evidence that actions performed by an
individual influence the sensorimotor memory processing and, in particular, the
integration process. We conducted 3 experiments that highlighted the multimodal
aspect of memory traces. The 1st experiment consisted of a short-term priming
paradigm based on 2 phases: a learning phase, consisting of the association
between a shape and a sound, and a test phase, examining the priming effect of
the shape seen in the learning phase on the processing of target tones. The
participants' motor response became a factor in Experiments 2 and 3, allowing us
to observe its influence on the integration between the shape and the sound. In
Experiment 1, we showed that (a) the prime associated with the sound in the
learning phase had an effect on target processing and (b) the component
reactivated by the prime was perceptual in nature (i.e., auditory). Experiment 2
showed that the participants' responses were faster when the association of a
shape and a sound had been learned with a motor response rather than without.
Experiment 3 showed that the integration process required the individual to act
while learning the association between the shape and the sound; otherwise no
integration effect was observed. Our results highlight the role of motor
responses as a necessary criterion for the integration process to take place.
(PsycINFO Database Record
PMID- 27505226
TI - Where to start? Bottom-up attention improves working memory by determining
encoding order.
AB - The present study aimed to characterize the mechanism by which working memory is
enhanced for items that capture attention because of their novelty or saliency
that is, via bottom-up attention. The first experiment replicated previous
research by corroborating that bottom-up attention directed to an item is
sufficient for enhancing working memory and, moreover, generalized the effect to
the domain of verbal working memory. The subsequent 3 experiments sought to
determine how bottom-up attention affects working memory. We considered 2
hypotheses: (1) Bottom-up attention enhances the encoded representation of the
stimulus, similar to how voluntary attention functions, or (2) It affects the
order of encoding by shifting priority onto the attended stimulus. By
manipulating how stimuli were presented (simultaneous/sequential display) and
whether the cue predicted the tested items, we found evidence that bottom-up
attention improves working memory performance via the order of encoding
hypothesis. This finding was observed across change detection and free recall
paradigms. In contrast, voluntary attention improved working memory regardless of
encoding order and showed greater effects on working memory. We conclude that
when multiple information sources compete, bottom-up attention prioritizes the
location at which encoding should begin. When encoding order is set, bottom-up
attention has little or no benefit to working memory. (PsycINFO Database Record
PMID- 27505227
TI - Differentiating global and local contour completion using a dot localization
paradigm.
AB - Competing theories of partially occluded object perception (amodal completion)
emphasize either relatively local contour relationships or global factors such as
symmetry. These disparate theories may reflect 2 separate processes: a low-level
contour interpolation process and a higher-order global recognition process. The
2 could be distinguished experimentally if only the former produces precise
representations of occluded object boundaries. Using a dot localization paradigm,
we measured the precision and accuracy of perceived object boundaries for
participants instructed to complete occluded objects with divergent local and
global interpretations. On each trial, a small red dot was flashed on top of an
occluder. Participants reported whether the dot fell inside or outside the
occluded object's boundaries. Interleaved, 2-up, 1-down staircases estimated
points on the psychometric function where the probability was .707 that the dot
would be seen as either outside or inside the occluded object's boundaries. The
results reveal that local contour interpolation produces precise and accurate
representations of occluded contours, and consistency across observers, but
completion according to global symmetry does not. These results support a
distinction between local, automatic contour interpolation processes and global
processes based on recognition from partial information. (PsycINFO Database
Record
PMID- 27505228
TI - Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV
Infected Patients Who Are about to Change to Tenofovir-Based First-Line
Antiretroviral Therapy? Programmatic Findings from Myanmar.
AB - BACKGROUND: WHO recommends that stavudine is phased out of antiretroviral therapy
(ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In
this context, the Integrated HIV Care Program, Myanmar, evaluated patients for
ART failure using HIV RNA viral load (VL) before making the change. We aimed to
determine prevalence and determinants of ART failure in those on first-line
treatment. METHODS: Patients retained on stavudine-based or zidovudine-based ART
for >12 months with no clinical/immunological evidence of failure were offered VL
testing from August 2012. Plasma samples were tested using real time PCR. Those
with detectable VL>250 copies/ml on the first test were provided with adherence
counseling and three months later a second test was performed with >1000
copies/ml indicating ART failure. We calculated the prevalence of ART failure and
adjusted relative risks (aRR) to identify associated factors using log binomial
regression. RESULTS: Of 4934 patients tested, 4324 (87%) had an undetectable VL
at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a
second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml
signifying ART failure. There were 108 who failed to have the second test.
Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2%
who did not follow the VL testing algorithm. Risk factors for ART failure were
age 15-24 years (aRR 2.4, 95% CI: 1.5-3.8) compared to 25-44 years and previous
ART in the private sector (aRR 1.6, 95% CI: 1.2-2.2) compared to the public
sector. CONCLUSIONS: This strategy of evaluating patients on first-line ART
before changing to TDF was feasible and identified a small proportion with ART
failure, and could be considered by HIV/AIDS programs in Myanmar and other
countries.
PMID- 27505229
TI - Association between reduced white matter integrity in the corpus callosum and
serotonin transporter gene DNA methylation in medication-naive patients with
major depressive disorder.
AB - Previous evidence suggests that the serotonin transporter gene (SLC6A4) is
associated with the structure of brain regions that are critically involved in
dysfunctional limbic-cortical network activity associated with major depressive
disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics
were used to investigate changes in white matter integrity in patients with MDD
compared with healthy controls. A possible association between structural
alterations in white matter tracts and DNA methylation of the SLC6A4 promoter
region was also assessed. Thirty-five medication-naive patients with MDD (mean
age: 40.34, male/female: 10/25) and age, gender and education level matched 49
healthy controls (mean age: 41.12, male/female: 15/34) underwent DTI. SLC6A4 DNA
methylation was also measured at five CpG sites of the promoter region, and the
cell type used was whole-blood DNA. Patients with MDD had significantly lower
fractional anisotropy (FA) values for the genu of the corpus callosum and body of
the corpus callosum than that in healthy controls (family-wise error corrected,
P<0.01). Significant inverse correlations were observed between SLC6A4 DNA
methylation and FA (CpG3, Pearson's correlation: r=-0.493, P=0.003) and axial
diffusivity (CpG3, Pearson's correlation: r=-0.478, P=0.004) values of the body
of the corpus callosum in patients with MDD. These results contribute to evidence
indicating an association between epigenetic gene regulation and structural brain
alterations in depression. Moreover, we believe this is the first report of a
correlation between DNA methylation of the SLC6A4 promoter region and white
matter integrity in patients with MDD.
PMID- 27505230
TI - Increased DNA and RNA damage by oxidation in patients with bipolar I disorder.
AB - The mechanisms underlying bipolar disorder (BD) and the associated medical burden
are unclear. Damage generated by oxidation of nucleosides may be implicated in BD
pathophysiology; however, evidence from in vivo studies is limited and the extent
of state-related alterations is unclear. This prospective study investigated for
we believe the first time the damage generated by oxidation of DNA and RNA
strictly in patients with type I BD in a manic or mixed state and subsequent
episodes and remission compared with healthy control subjects. Urinary excretion
of 8-oxo-deoxyguanosine (8-oxodG) and 8-oxo-guanosine (8-oxoGuo), valid markers
of whole-body DNA and RNA damage by oxidation, respectively, was measured in 54
patients with BD I and in 35 healthy control subjects using a modified
ultraperformance liquid chromatography and mass spectrometry assay. Repeated
measurements were evaluated in various affective phases during a 6- to 12-month
period and compared with repeated measurements in healthy control subjects.
Independent of lifestyle and demographic variables, a 34% (P<0.0001) increase in
RNA damage by oxidation across all affective states, including euthymia, was
found in patients with BD I compared with healthy control subjects. Increases in
DNA and RNA oxidation of 18% (P<0.0001) and 8% (P=0.02), respectively, were found
in manic/hypomanic states compared with euthymia, and levels of 8-oxodG decreased
15% (P<0.0001) from a manic or mixed episode to remission. The results indicate a
role for DNA and RNA damage by oxidation in BD pathophysiology and a potential
for urinary 8-oxodG and 8-oxoGuo to function as biological markers of diagnosis,
state and treatment response in BD.
PMID- 27505232
TI - WGO La Paz Training Center and Gastro 2016: EGHS-WGO International Congress in
Abu Dhabi.
PMID- 27505231
TI - Impact of polygenic schizophrenia-related risk and hippocampal volumes on the
onset of psychosis.
AB - Alterations in hippocampal volume are a known marker for first-episode psychosis
(FEP) as well as for the clinical high-risk state. The Polygenic Schizophrenia
related Risk Score (PSRS), derived from a large case-control study, indicates the
polygenic predisposition for schizophrenia in our clinical sample. A total of 65
at-risk mental state (ARMS) and FEP patients underwent structural magnetic
resonance imaging. We used automatic segmentation of hippocampal volumes using
the FSL-FIRST software and an odds-ratio-weighted PSRS based on the publicly
available top single-nucleotide polymorphisms from the Psychiatric Genomics
Consortium genome-wide association study (GWAS). We observed a negative
association between the PSRS and hippocampal volumes (beta=-0.42, P=0.01, 95%
confidence interval (CI)=(-0.72 to -0.12)) across FEP and ARMS patients.
Moreover, a higher PSRS was significantly associated with a higher probability of
an individual being assigned to the FEP group relative to the ARMS group
(beta=0.64, P=0.03, 95% CI=(0.08-1.29)). These findings provide evidence that a
subset of schizophrenia risk variants is negatively associated with hippocampal
volumes, and higher values of this PSRS are significantly associated with FEP
compared with the ARMS. This implies that FEP patients have a higher genetic risk
for schizophrenia than the total cohort of ARMS patients. The identification of
associations between genetic risk variants and structural brain alterations will
increase our understanding of the neurobiology underlying the transition to
psychosis.
PMID- 27505233
TI - Manganese-Catalyzed Carboacylations of Alkenes with Alkyl Iodides.
AB - A manganese-catalyzed carboacylation of alkenes with alkyl iodides and carbon
monoxide is described. This carbonylative difunctionalization uses both primary
and secondary alkyl iodides in reactions with a diverse array of cyclic and
acyclic substrates. Examples of successful applications to the synthesis of five
, six-, and seven-membered rings are provided. The inexpensive, first-row
catalytic system and mild reaction conditions are expected to facilitate
applications in complex synthesis.
PMID- 27505234
TI - Phenotypic Variations in the Foliar Chemical Profile of Persea americana Mill.
cv. Hass.
AB - The Hass avocado tree Persea americana cv. Hass was derived from a single hybrid
tree of P. americana var. drymifolia and P. americana var. guatemalensis, and it
is propagated clonally by grafting. This cultivar is the most widely planted in
the world but its profile of secondary metabolites has been studied rarely
despite of its importance in plant protection. We illustrate the variability of
the volatilome of mature leaves by describing the average chemical composition
and the phenotypic variability found in 70 trees. Contrary to the uniformity
expected in the Hass cultivar, high variability coefficients were found for most
of the 36 detected foliar volatile compounds; furthermore we found six chemotypes
grouping the foliar phenotypes of the sampled trees using hierarchical cluster
analysis. About 48% of trees were grouped in one chemotype; five chemotypes
grouped the remaining trees. The compounds that determined these chemotypes were:
estragole, alpha-farnesene, beta-caryophyllene, germacrene D, alpha-cubebene and
eugenol. This striking variation in a cultivar propagated clonally is discussed
in terms of somatic mutation.
PMID- 27505235
TI - Salamandra.
AB - Beukema et al. Introduce the genus salamandra comprising the well-known fire
salamanders.
PMID- 27505236
TI - The origin of ambling horses.
AB - Horseback riding is the most fundamental use of domestic horses and has had a
huge influence on the development of human societies for millennia. Over time,
riding techniques and the style of riding improved. Therefore, horses with the
ability to perform comfortable gaits (e.g. ambling or pacing), so-called 'gaited'
horses, have been highly valued by humans, especially for long distance travel.
Recently, the causative mutation for gaitedness in horses has been linked to a
substitution causing a premature stop codon in the DMRT3 gene (DMRT3_Ser301STOP)
[1]. In mice, Dmrt3 is expressed in spinal cord interneurons and plays an
important role in the development of limb movement coordination [1]. Genotyping
the position in 4396 modern horses from 141 breeds revealed that nowadays the
mutated allele is distributed worldwide with an especially high frequency in
gaited horses and breeds used for harness racing [2]. Here, we examine historic
horse remains for the DMRT3 SNP, tracking the origin of gaitedness to Medieval
England between 850 and 900 AD. The presence of the corresponding allele in
Icelandic horses (9(th)-11(th) century) strongly suggests that ambling horses
were brought from the British Isles to Iceland by Norse people. Considering the
high frequency of the ambling allele in early Icelandic horses, we believe that
Norse settlers selected for this comfortable mode of horse riding soon after
arrival. The absence of the allele in samples from continental Europe (including
Scandinavia) at this time implies that ambling horses may have spread from
Iceland and maybe also the British Isles across the continent at a later date.
PMID- 27505237
TI - What is the association between religious affiliation and children's altruism?
AB - Decety et al.[1] examined the relationships between household religiosity and
sociality in children sampled from six countries. We were keenly interested in
Decety et al.[1]'s conclusions about a negative relationship between religiosity
and generosity - measured with the Dictator Game - as our team has investigated
related questions, often with potentially contrasting findings [2-5]. We argue
here that, after addressing peculiarities in their analyses, Decety et al.[1]'s
data are consistent with a different interpretation.
PMID- 27505238
TI - Neuroscience: Hunger Pangs in the Fly Brain.
AB - Which neurons in the brain become engaged when the body is deprived of food? A
new study addresses this question using the vinegar fly Drosophila melanogaster,
examining a group of neurons in the brain that show alterations in neural
activity when flies are satiated or starved.
PMID- 27505239
TI - Autophagy: Press and Push for Destruction.
AB - Recent publications illustrate an extensive crosstalk between the actin
cytoskeleton and autophagy, a program for self-digestion. Actin polymerization
provides a pushing force for organelle shaping and trafficking during autophagy,
but the cytoskeleton is also targeted by autophagy under mechanical strain.
PMID- 27505240
TI - Retinal Physiology: Non-Bipolar-Cell Excitatory Drive in the Inner Retina.
AB - The long-held view that bipolar cells provide the exclusive excitatory drive to
the mammalian inner retina has been challenged: new studies indicate that,
instead, at least two cells that lack the dendrites characteristic for bipolar
cells, and therefore resemble amacrine cells, excite inner retinal circuits using
glutamate.
PMID- 27505241
TI - Ecology: The Upside-Down World of Coral Reef Predators.
AB - Examination of a large aggregation of sharks demonstrates that trophic pyramids
with greater amounts of high-level predators than prey can occur on coral reefs.
This is possible because the high-level predators obtain food from sources
outside their home location.
PMID- 27505242
TI - Chromatin: Polycomb Group SAMs Unite.
AB - Polycomb Group (PcG) proteins assemble a chromatin state that maintains
developmental gene repression. A new study combining structure and in vivo
analysis details a molecular network from DNA recognition to PcG recruitment,
highlighting the essential role of Sterile Alpha Motifs.
PMID- 27505243
TI - Neuroscience: Peeking Under the Sombrero.
AB - A recent study has introduced a new analytical approach to understanding neural
circuits which has revealed previously hidden neural interactions in a large
population of cells in the primate retina. The neural circuit described likely
contributes to encoding visual motion.
PMID- 27505244
TI - Wound Signaling: Monkeywrenching Macrophage Migration with Microscopes, Movies,
and Math.
AB - Drosophila hemocytes (blood cells) have emerged as a powerful system to image
wound-induced inflammatory responses in vivo. New work reveals that layering
mathematical modeling on top of imaging may be the most powerful tool yet for
determining the properties of wound-induced signals.
PMID- 27505245
TI - Behavior: Knowing When to Walk Away, Knowing When to Run.
AB - A new model has been proposed indicating that humans and other animals weigh the
metabolic cost of pursuit in deciding how fast to move toward a given reward,
providing a powerful framework for understanding behavior.
PMID- 27505246
TI - Actomyosin Ring Formation and Tension Generation in Eukaryotic Cytokinesis.
AB - Cell division facilitated by a contractile ring is an almost universal feature
across all branches of cellular life, with the notable exception of higher
plants. In all organisms that use a contractile ring for cell division, the
process of cytokinesis can be divided into four distinct stages. Firstly, the
cell needs to specify a location at which to place the cell division ring to
ensure proper separation of the cell contents into two daughter cells. Secondly,
the cell needs to be able to transport all the necessary components to this
region, and construct the cell division ring reliably and efficiently. Thirdly,
the cell division ring needs to generate contractile stress in a regulated
manner, to physically cleave the mother cell into two daughter cells. Finally,
the ring must be disassembled to allow for the final abscission and separation of
the daughter cells. In this review, we will discuss some of the proposed
mechanisms by which eukaryotic cells are able to complete the first three of
these stages. While there is a good understanding of the mechanisms of division
site specification in most organisms, and the mechanisms of actomyosin ring
formation are well studied in fission and budding yeast, there is relatively poor
understanding of how actomyosin interactions are able to generate contractile
stresses during ring constriction, although a number of models have been
proposed. We also discuss a number of myosin motor-independent mechanisms that
have been proposed to generate contractile stress in various organisms.
PMID- 27505248
TI - Nonfocal Symptoms in Patients with Transient Ischemic Attack or Ischemic Stroke:
Occurrence, Clinical Determinants, and Association with Cardiac History.
AB - BACKGROUND: Transient ischemic attacks (TIAs) accompanied by nonfocal symptoms
are associated with a higher risk of cardiovascular events, in particular cardiac
events. Reported frequencies of TIAs accompanied by nonfocal symptoms range from
18 to 53%. We assessed the occurrence of nonfocal symptoms in patients with TIA
or minor ischemic stroke in a neurological outpatient clinic in terms of clinical
determinants, cardiac history, and atrial fibrillation (AF). METHODS: We included
1,265 consecutive patients with TIA or minor stroke who visited the outpatient
clinic. During these visits, we systematically asked for nonfocal symptoms.
Nonfocal symptoms included decreased consciousness, amnesia, positive visual
phenomena, non-rotatory dizziness, and paresthesias. Relative risks for the
presence of nonfocal symptoms in relation to clinical determinants, AF, and
cardiac history were calculated. RESULTS: In 243 (19%) of 1,265 patients, TIA or
minor ischemic stroke was accompanied by one or more nonfocal symptoms. Non
rotatory dizziness, paresthesia, and amnesia were the most common nonfocal
symptoms. In patients with an event of the posterior circulation or obesity, the
qualifying TIA or minor stroke was more frequently accompanied by nonfocal
symptoms, and in patients with significant carotid stenosis, nonfocal symptoms
occurred less frequently. AF was related only with amnesia. CONCLUSION: Nonfocal
symptoms are present in one out of 5 patients with TIA or ischemic stroke, in
particular when located in the posterior circulation. A cardiac history or AF was
not directly related to nonfocal symptoms. A heterogeneous etiology is suggested.
PMID- 27505247
TI - CCL21/CCR7 Axis Contributed to CD133+ Pancreatic Cancer Stem-Like Cell Metastasis
via EMT and Erk/NF-kappaB Pathway.
AB - BACKGROUND: Tumor metastasis is driven by malignant cells and stromal cell
components of the tumor microenvironment. Cancer stem cells (CSCs) are thought to
be responsible for metastasis by altering the tumor microenvironment. Epithelial
mesenchymal transition (EMT) processes contribute to specific stages of the
metastatic cascade, promoted by cytokines and chemokines secreted by stromal cell
components in the tumor microenvironment. C-C chemokine receptor 7 (CCR7)
interacts with its ligand, chemokine ligand 21(CCL21), to mediate metastasis in
some cancer cells lines. This study investigated the role of CCL21/CCR7 in
promoting EMT and metastasis of cluster of differentiation 133+ (CD133+)
pancreatic cancer stem-like cells. METHODS: Panc-1, AsPC-1, and MIA PaCa-2
pancreatic cancer cells were selected because of their aggressive invasive
potentials. CCR7 expression levels were examined in total, CD133+ and CD133- cell
fractions by Immunofluorescence analysis and real time-quantitative polymerase
chain reaction (RT-qPCR). The role of CCL21/CCR7 in mediating metastasis and
survival of CD133+ pancreatic cancer stem-like cells was detected by Transwell
assays and flow cytometry, respectively. EMT and lymph node metastasis related
markers (E-cadherin, N- cadherin, LYVE-1) were analyzed by western blot. CCR7
expression levels were analyzed by immunohistochemical staining and RT-qPCR in
resected tumor tissues, metastatic lymph nodes, normal lymph nodes and adjacent
normal tissues from patients with pancreatic carcinoma. RESULTS: CCR7 expression
was significantly increased in CD133+ pancreatic cancer stem-like cells, resected
pancreatic cancer tissues, and metastatic lymph nodes, compared with CD133-
cancer cells, adjacent normal tissues and normal lymph nodes, respectively.
CCL21/CCR7 promoted metastasis and survival of CD133+ pancreatic cancer stem-like
cells and regulated CD133+ pancreatic cancer stem-like cells metastasis by
modulating EMT and Erk/NF-kappaB pathway. CONCLUSIONS: These results indicate a
specific role for CCL21/CCR7 in promoting EMT and metastasis in CD133+ pancreatic
cancer stem-like cells. Furthermore the data also indicated the potential
importance of developing therapeutic strategies targeting cancer stem-like cells
and CCL21/CCR7 for reducing metastasis.
PMID- 27505249
TI - Determinants of acquired activated protein C resistance and D-dimer in breast
cancer.
AB - BACKGROUND: We have previously reported acquired activated protein C (APC)
resistance and elevated plasma D-dimer levels in breast cancer patients. Here, we
aimed to identify phenotypic and genetic determinants that contribute to the
acquired APC resistance and increased D-dimer levels in breast cancer. Healthy
controls served as reference. We also addressed whether higher APC resistance or
D-dimer levels could be potential markers of clinicopathological breast cancer
characteristics. MATERIALS AND METHODS: 358 breast cancer patients and 273
healthy controls were enrolled and hemostatic plasma parameters were determined;
factor (F) V, FVIII, FIX, FX, fibrinogen, von Willebrand factor (VWF), normalized
APC sensitivity ratio (n-APC-sr), protein C, protein S, antithrombin, tissue
factor pathway inhibitor (TFPI), and D-dimer. Common single nucleotide
polymorphisms were genotyped in coagulation-related genes in the breast cancer
patients. RESULTS: The phenotypic hemostatic factors explained 25% and 31% of the
variability in acquired APC resistance and D-dimer levels, respectively, in the
breast cancer patients. Fibrinogen (beta=-0.35, P<0.001), protein C (beta=0.28,
P<0.001), and FIX (beta=0.22, P=0.026) were identified as determinants of n-APC
sr (in FV Leiden non-carriers), whereas TFPI (beta=0.28, P<0.001), antithrombin
(beta=-0.25, P<0.001), and FX (beta=0.15, P=0.040) were the major determinants of
D-dimer. Moreover, borderline higher APC resistance (>75th percentile) was found
in patients with triple negative tumors (odds ratio (OR) 1.97, 95% CI 0.99-3.90).
CONCLUSIONS: This study reports phenotypic hemostatic parameters that determine
acquired APC resistance and D-dimer levels in breast cancer patients. The
explanatory power was modest, however, our findings are hypothesis generating and
may contribute to further understand the background for cancer associated
coagulopathy and thrombosis.
PMID- 27505250
TI - Isolation of All CD44 Transcripts in Human Epidermis and Regulation of Their
Expression by Various Agents.
AB - CD44, a cell surface proteoglycan, is involved in many biological events. CD44
transcripts undergo complex alternative splicing, resulting in many functionally
distinct isoforms. To date, however, the nature of these isoforms in human
epidermis has not been adequately determined. In this study, we isolated all CD44
transcripts from normal human epidermis, and studied how their expressions are
regulated. By RT-PCR, we found that a number of different CD44 transcripts were
expressed in human epidermis, and we obtained all these transcripts from DNA
bands in agarose and acrylamide gels by cloning. Detailed sequence analysis
revealed 18 CD44 transcripts, 3 of which were novel. Next, we examined effects of
10 different agents on the expression of CD44 transcripts in cultured human
keratinocytes, and found that several agents, particularly epidermal growth
factor, hydrogen peroxide, phorbol 12-myristate 13-acetate, retinoic acid,
calcium and fetal calf serum differently regulated their expressions in various
patterns. Furthermore, normal and malignant keratinocytes were found to produce
different CD44 transcripts upon serum stimulation and subsequent starvation,
suggesting that specific CD44 isoforms are involved in tumorigenesis via
different CD44-mediated biological pathways.
PMID- 27505252
TI - Oliguria and Biomarkers of Acute Kidney Injury: Star Struck Lovers or Strangers
in the Night?
AB - Oliguria is a common phenomenon that is found in hospitalized patients . Although
a rapid reduction in urine excretion rate may reflect a precipitous fall in the
glomerular filtration rate, in many cases it may not. Given the common
physiological finding of oliguria, we explore the relationship between the
functional biomarker of renal injury (oliguria) with the increasing number of
markers of renal injury to see if this combination may aid in risk
stratification. (c) 2016 S. Karger AG, Basel.
PMID- 27505251
TI - Del1 Knockout Mice Developed More Severe Osteoarthritis Associated with Increased
Susceptibility of Chondrocytes to Apoptosis.
AB - OBJECTIVE: We identified significant expression of the matricellular protein,
DEL1, in hypertrophic and mature cartilage during development. We hypothesized
that this tissue-specific expression indicated a biological role for DEL1 in
cartilage biology. METHODS: Del1 KO and WT mice had cartilage thickness evaluated
by histomorphometry. Additional mice underwent medial meniscectomy to induce
osteoarthritis, and were assayed at 1 week for apoptosis by TUNEL staining and at
8 weeks for histology and OA scoring. In vitro proliferation and apoptosis assays
were performed on primary chondrocytes. RESULTS: Deletion of the Del1 gene led to
decreased amounts of cartilage in the ears and knee joints in mice with otherwise
normal skeletal morphology. Destabilization of the knee led to more severe OA
compared to controls. In vitro, DEL1 blocked apoptosis in chondrocytes.
CONCLUSION: Osteoarthritis is among the most prevalent diseases worldwide and
increasing in incidence as our population ages. Initiation begins with an injury
resulting in the release of inflammatory mediators. Excessive production of
inflammatory mediators results in apoptosis of chondrocytes. Because of the
limited ability of chondrocytes to regenerate, articular cartilage deteriorates
leading to the clinical symptoms including severe pain and decreased mobility. No
treatments effectively block the progression of OA. We propose that direct
modulation of chondrocyte apoptosis is a key variable in the etiology of OA, and
therapies aimed at preventing this important step represent a new class of
regenerative medicine targets.
PMID- 27505253
TI - Building Global Capacity for Conducting Operational Research Using the SORT IT
Model: Where and Who?
AB - SETTING: Research capacity is weakest in low and middle-income countries (LMICs)
where operational research is highly relevant and needed. Structured Operational
Research and Training Initiative (SORT IT) courses have been developed to train
participants to conduct and publish operational research and influence policy and
practice. Twenty courses were completed in Asia, Africa, Europe and the South
Pacific between 2009 and 2014. OBJECTIVES: In the 20 completed SORT IT courses,
to assess where the research was conducted, who was trained, who became
facilitators in subsequent courses and course outcomes. DESIGN: A cohort study of
completed SORT IT courses. RESULTS: There were 236 participants (41% female)
including 64 nationalities who conducted research in 59 countries, mostly from
Asia and Africa (mean course duration = 9.7 months). Most participants (68%) were
from government health programs and non-governmental agencies. A total of
213(90%) participants completed all milestones successfully with 41(19%) becoming
subsequent course facilitators, 88% of whom were from LMICs. Of 228 manuscripts
submitted to scientific journals, 197(86%) were either published or in press; in
86%, the principal investigator (first author) was a LMIC national. Papers were
published in 23 scientific journals (impact factor 0.5-4.4) and covered 21
disease categories (median publication time = 5.7 months). Published papers (186)
had 94,794 cumulative article views/downloads. Article views/downloads for
immediate open access articles were double those from closed access journals.
CONCLUSION: The SORT IT model has been effective in training personnel to produce
relevant operational research in LMICs. It merits continued commitment and
support for further scale-up and development.
PMID- 27505254
TI - Pollinator Foraging Adaptation and Coexistence of Competing Plants.
AB - We use the optimal foraging theory to study coexistence between two plant species
and a generalist pollinator. We compare conditions for plant coexistence for non
adaptive vs. adaptive pollinators that adjust their foraging strategy to maximize
fitness. When pollinators have fixed preferences, we show that plant coexistence
typically requires both weak competition between plants for resources (e.g.,
space or nutrients) and pollinator preferences that are not too biased in favour
of either plant. We also show how plant coexistence is promoted by indirect
facilitation via the pollinator. When pollinators are adaptive foragers,
pollinator's diet maximizes pollinator's fitness measured as the per capita
population growth rate. Simulations show that this has two conflicting
consequences for plant coexistence. On the one hand, when competition between
pollinators is weak, adaptation favours pollinator specialization on the more
profitable plant which increases asymmetries in plant competition and makes their
coexistence less likely. On the other hand, when competition between pollinators
is strong, adaptation promotes generalism, which facilitates plant coexistence.
In addition, adaptive foraging allows pollinators to survive sudden loss of the
preferred plant host, thus preventing further collapse of the entire community.
PMID- 27505255
TI - Oxidation Ability of Plasmon-Induced Charge Separation Evaluated on the Basis of
Surface Hydroxylation of Gold Nanoparticles.
AB - The oxidation ability of plasmonic photocatalysts, which has its origins in
plasmon-induced charge separation and has not yet been studied quantitatively and
systematically, is important for designing practical photocatalytic systems.
Oxidation ability was investigated on the basis of surface hydroxylation of Au
nanoparticles on TiO2 at various irradiation wavelengths and electrolyte pH
values. The reaction proceeds only when the sum of the flat band potential of
TiO2 and the irradiated photon energy is close to, or more positive than, the
theoretical potential for the reaction.
PMID- 27505256
TI - The role of progranulin in arthritis.
AB - Progranulin (PGRN) is a growth factor with a unique beads-on-a-string structure
that is involved in multiple pathophysiological processes, including anti
inflammation, tissue repair, wound healing, neurodegenerative diseases, and
tumorigenesis. This review presents up-to-date information concerning recent
studies on the role of PGRN in inflammatory arthritis and osteoarthritis, with a
special focus on the involvement of the interactions and interplay between PGRN
and tumor necrosis factor receptor (TNFR) family members in regulating such
musculoskeletal diseases. In addition, this paper highlights the applications of
atsttrin, an engineered protein comprising three TNFR-binding fragments of PGRN,
as a promising intervention in treating arthritis.
PMID- 27505257
TI - Clinician's Commentary on Laliberte et al.(1).
PMID- 27505258
TI - Diabetes Prevention Through Antiviral Treatment in Biobreeding Rats.
AB - A picornavirus (Ljungan virus) has been associated with diabetes in its wild
rodent reservoir and in diabetes-prone biobreeding (DP-BB) rats. We attempted to
alter the development of diabetes in DP-BB rats using two anti-picornavirus
compounds (pleconaril and APO-N039), singly or in combination. Antiviral therapy
was initiated 2 weeks before expected onset of diabetes. Pleconaril or APO-N039
alone did not affect the debut of diabetes. However, animals receiving a
combination of both compounds were protected for at least the entire period of
treatment (4 weeks after expected time of diabetes onset). Immunohistochemistry
demonstrated that the presence and distribution of virus antigen in the
pancreatic islets coincided with the clinical status of the animal. Data indicate
that a treatable picornavirus can be involved in the cellular assault resulting
in diabetes and in these cases the disease mechanism appears to involve a virus
present in the pancreatic beta cell mass itself.
PMID- 27505259
TI - Formation of Interfacial Janus Nanomicelles by Reactive Blending and Their
Compatibilization Effects on Immiscible Polymer Blends.
AB - Micellization of in situ formed graft copolymers during reactive blending is
commonly observed. Numerous studies have been carried out to minimize the
formation of micelles and enhance emulsification efficiency. Herein, we
investigated the formation of interfacial Janus nanomicelles (JNMs) and their
compatibilization effects on immiscible polymer blends when reactive graft
copolymers (RGCs) are used as compatibilizers. Poly(styrene-co-glycidyl
methacrylate)-graft-poly(methyl methacrylate) RGCs were synthesized and used as
compatibilizers for immiscible poly(l-lactide) (PLLA)/poly(vinylidene fluoride)
(PVDF) blends. Numerous nanomicelles were formed in situ during melt blending by
grafting of PLLA onto the RGCs. The formation and location of JNMs depended not
only on the molecular architecture of the RGCs but also on the melt processing
sequence and molecular weight of the components. Interfacial JNMs can effectively
improve the miscibility of polymer blends, thereby enhancing the performance of
immiscible polymer blends.
PMID- 27505260
TI - Supramolecular Spangling, Crocheting, and Knitting of Functionalized Pyrene
Molecules on a Silver Surface.
AB - Pyrenes, as photoactive polycyclic aromatic hydrocarbons (PAHs), represent
promising modules for the bottom-up assembly of functional nanostructures. Here,
we introduce the synthesis of a family of pyrene derivatives peripherally
functionalized with pyridin-4-ylethynyl termini and comprehensively characterize
their self-assembly abilities on a smooth Ag(111) support by scanning tunneling
microscopy. By deliberate selection of number and geometric positioning of the
pyridyl-terminated substituents, two-dimensional arrays, one-dimensional
coordination chains, and chiral, porous kagome-type networks can be tailored. A
comparison to phenyl-functionalized reference pyrenes, not supporting the self
assembly of ordered structures at low coverage, highlights the role of the
pyridyl moieties for supramolecular crocheting and knitting. Furthermore, we
demonstrate the selective spangling of pores in the two-dimensional pyrene
assemblies by a distinct number of iodine atoms as guests by atomically resolved
imaging and complementary X-ray photoelectron spectroscopy.
PMID- 27505261
TI - Manganese-Promoted Ring-Opening Hydrazination of Cyclobutanols: Synthesis of
Alkyl Hydrazines.
AB - We herein disclose an efficient manganese-promoted hydrazination of cyclobutanols
through cyclic C-C bond cleavage. The ring opening occurs under mild reaction
conditions, readily affording a variety of alkyl hydrazines in synthetically
useful yields and exclusive regioselectivities. The chain reaction mechanism
involving the addition of alkyl carbon radical to azodicarboxylate is proposed.
PMID- 27505262
TI - Investigating the evolution of summertime secondary atmospheric pollutants in
urban Beijing.
AB - Understanding the formation of tropospheric ozone (O3) and secondary particulates
is essential for controlling secondary pollution in megacities. Intensive
observations were conducted to investigate the evolution of O3, nitrate (NO3-),
sulfate (SO42-) and oxygenated organic aerosols ((OOAs), a proxy for secondary
organic aerosols) and the interactions between O3, NOx oxidation products (NOz)
and OOA in urban Beijing in August 2012. The O3 concentrations exhibited similar
variations at both the urban and urban background sites in Beijing. Regarding the
O3 profile, the O3 concentrations increased with increasing altitude. The peaks
in O3 on the days exceeding the 1h or 8h O3 standards (polluted days) were
substantially wider than those on normal days. Significant increases in the NOz
mixing ratio (i.e., NOy - NOx) were observed between the morning and early
afternoon, which were consistent with the increasing oxidant level. A discernable
NO3- peak was also observed in the morning on the polluted days, and this peak
was attributed to vertical mixing and strong photochemical production. In
addition, a SO42- peak at 18:00 was likely caused by a combination of local
generation and regional transport. The OOA concentration cycle exhibited two
peaks at approximately 10:00 and 19:00. The OOA concentrations were correlated
well with SO42- ([OOA]=0.55*[SO42-]+2.1, r2=0.69) because they both originated
from secondary transformations that were dependent on the ambient oxidization
level and relative humidity. However, the slope between OOA and SO42- was only
0.35, which was smaller than the slope observed for all of the OOA and SO42-
data, when the RH ranged from 40 to 50%. In addition, a photochemical episode was
selected for analysis. The results showed that regional transport played an
important role in the evolution of the investigated secondary pollutants. The
measured OOA and Ox concentrations were well correlated at the daily scale,
whereas the hourly OOA and Ox concentrations were insignificantly correlated in
urban Beijing. The synoptic situation and the differences in the VOC oxidation
contributing to O3 and SOAs may have resulted in the differences among the
correlations between OOA and Ox at different time scale. We calculated OOA
production rates using the photochemical age (defined as -log10(NOx/NOy)) in
urban plumes. The CO-normalized OOA concentration increased with increasing
photochemical age, with production rates ranging from 1.1 to 8.5MUgm-3ppm-1h-1
for the plume from the NCP.
PMID- 27505263
TI - Persistence of glyphosate and aminomethylphosphonic acid in loess soil under
different combinations of temperature, soil moisture and light/darkness.
AB - The dissipation kinetics of glyphosate and its metabolite aminomethylphosphonic
acid (AMPA) were studied in loess soil, under biotic and abiotic conditions, as
affected by temperature, soil moisture (SM) and light/darkness. Nonsterile and
sterile soil samples were spiked with 16mgkg-1 of glyphosate, subjected to three
SM contents (20% WHC, 60% WHC, saturation), and incubated for 30days at 5 degrees
C and 30 degrees C, under dark and light regimes. Glyphosate and AMPA dissipation
kinetics were fit to single-first-order (SFO) or first-order-multicompartment
(FOMC) models, per treatment combination. AMPA kinetic model included both the
formation and decline phases. Glyphosate dissipation kinetics followed SFO at 5
degrees C, but FOMC at 30 degrees C. AMPA followed SFO dissipation kinetics for
all treatments. Glyphosate and AMPA dissipation occurred mostly by microbial
activity. Abiotic processes played a negligible role for both compounds. Under
biotic conditions, glyphosate dissipation and AMPA formation/dissipation were
primarily affected by temperature, but also by SM. Light regimes didn't play a
significant role. Glyphosate DT50 varied between 1.5 and 53.5days, while its DT90
varied between 8.0 and 280days, depending on the treatment. AMPA persisted longer
in soil than glyphosate, with its DT50 at 30 degrees C ranging between 26.4 and
44.5days, and its DT90 between 87.8 and 148days. The shortest DT50/DT90 values
for both compounds occurred at 30 degrees C and under optimal/saturated moisture
conditions, while the largest occurred at 5 degrees C and reaching drought stress
conditions. Based on these results, we conclude that glyphosate and AMPA
dissipate rapidly under warm and rainy climate conditions. However, repeated
glyphosate applications in fallows or winter crops in countries where cold and
dry winters normally occur could lead to on-site soil pollution, with consequent
potential risks to the environment and human health. To our knowledge, this study
is the first evaluating the combined effect of temperature, soil moisture and
light/dark conditions on AMPA formation/dissipation kinetics and behaviour.
PMID- 27505265
TI - Ecotoxicological water assessment of an estuarine river from the Brazilian
Northeast, potentially affected by industrial wastewater discharge.
AB - Water pollution generated by industrial effluents discharge is a threat to the
maintenance of aquatic ecosystems and human development. The Jundiai River
estuarine, located in Northeast Brazil, receives an industrial pretreated
effluent load from the city of Macaiba/RN/Brazil. The present study aimed to
assess the water quality of this water reservoir through i) physicochemical
characterization, ii) quantification of metal concentration and iii) by an
ecotoxicological assessment carried out using Mysidopsis juniae and Pomacea
lineata. The study was performed throughout the period comprising May to
September 2014. Physicochemical variables such as chloride, total solids and
electrical conductivity presented values in the waste discharge point,
significantly different with those located out of the waste releasing point.
Apart from that, metal concentration showed variable behavior throughout the
monitored period. Levels of Al, Fe, Cu, Cd, Cr, Ni, Pb and Ag were over the
considered guidelines. Both natural and anthropogenic sources seem to be involved
in the resulting environmental scenario. A reduction in the fecundity rate (using
Mysidopsis juniae) along with an increase in mortality rate (in both species) was
observed ratifying the presence of toxic substances in this water reservoir.
Moreover, a correlation analysis stated an association of the aforementioned
toxicological effects with the delivery of industrial waste products. The
ecotoxicological assessment performed highlighted the presence of toxic
substance/s in water from the Jundiai River. Especially as a consequence of
industrial activity, a fact that might threaten the bioma and, therefore, the
human health of the population settled in the studied region.
PMID- 27505264
TI - Entomopathogenic nematode food webs in an ancient, mining pollution gradient in
Spain.
AB - Mining activities pollute the environment with by-products that cause
unpredictable impacts in surrounding areas. Cartagena-La Union mine (Southeastern
Spain) was active for >2500years. Despite its closure in 1991, high
concentrations of metals and waste residues remain in this area. A previous study
using nematodes suggested that high lead content diminished soil biodiversity.
However, the effects of mine pollution on specific ecosystem services remain
unknown. Entomopathogenic nematodes (EPN) play a major role in the biocontrol of
insect pests. Because EPNs are widespread throughout the world, we speculated
that EPNs would be present in the mined areas, but at increased incidence with
distance from the pollution focus. We predicted that the natural enemies of
nematodes would follow a similar spatial pattern. We used qPCR techniques to
measure abundance of five EPN species, five nematophagous fungi species, two
bacterial ectoparasites of EPNs and one group of free-living nematodes that
compete for the insect-cadaver. The study comprised 193 soil samples taken from
mining sites, natural areas and agricultural fields. The highest concentrations
of iron and zinc were detected in the mined area as was previously described for
lead, cadmium and nickel. Molecular tools detected very low numbers of EPNs in
samples found to be negative by insect-baiting, demonstrating the importance of
the approach. EPNs were detected at low numbers in 13% of the localities, without
relationship to heavy-metal concentrations. Only Acrobeloides-group nematodes
were inversely related to the pollution gradient. Factors associated with
agricultural areas explained 98.35% of the biotic variability, including EPN
association with agricultural areas. Our study suggests that EPNs have adapted to
polluted habitats that might support arthropod hosts. By contrast, the
relationship between abundance of Acrobeloides-group and heavy-metal levels,
revealed these taxa as especially well suited bio-indicators of soil mining
pollution.
PMID- 27505266
TI - Measurement of volatile organic compounds (VOCs) in libraries and archives in
Florence (Italy).
AB - Indoor air samples from libraries and archives in Florence, Italy, were collected
and analysed for a variety of volatile organic compounds. The aim was to perform
a characterisation of the indoor air quality, and try to elucidate if there are
VOCs that may cause or result from the determination of the cultural heritage
institutions. All compounds of interest were regularly detected, with BTEXs
(Benzene, Toluene, Ethylbenzene, Xylenes) being the most abundant and followed by
cyclic volatile methylsiloxanes, aldehydes, terpenes and organic acids. The
prevalence and qualitative characteristics, such as concentrations, profiles and
indoor/outdoor ratios of BTEXs underline the important influence of the outdoor
air infiltrations on the indoor air concentrations. Acetic acid that is a
substance that can oxidise books and other exposed objects was detected at
concentrations ranging between 1.04 and 18.9MUgm-3, while furfural, that is a
known marker of paper degradation, was constantly present at concentrations that
ranged between 5.26 and 32.6MUgm-3. This work shows the importance that indoor
air quality monitoring campaigns can have in order to give early warning to
cultural heritage institution managers about the impact that indoor air quality
can have on exposed and/or preserved objects.
PMID- 27505267
TI - Impact of Behavioral Symptoms in Dementia Patients on Depression in Daughter and
Daughter-in-Law Caregivers.
AB - BACKGROUND: One caregiver relationship that has been neglected in caregiver
depression research is the daughter-in-law. Compared with Western countries, in
which those who are closer in familial relationships such as the spouse or child
usually take care of the patient, in many Asian countries, the daughter-in-law
often assumes the caretaker role. However, not much research has been done on how
this relationship may result in different caregiver outcomes. We sought to
identify whether the association between patient characteristics and caregiver
depressive symptoms differs according to the familial relationship between
caregiver and patient. MATERIALS AND METHODS: Ninety-five daughter (n = 47) and
daughter-in-law (n = 48) caregivers of dementia patients were asked to report
their own depressive symptoms and patient behavioral symptoms. Patients'
cognitive abilities, daily activities, and global dementia ratings were obtained.
Hierarchical linear regression was employed to determine predictors of depressive
symptoms. RESULTS: Daughters-in-law had marginally higher depressive scores.
After adjusting for caregiver and patient characteristics, in both groups,
greater dependency in activities of daily living and more severe and frequent
behavioral symptoms predicted higher caregiver depressive scores. However,
greater severity and frequency of behavioral symptoms predicted depression to a
greater degree in daughters compared with daughters-in-law. CONCLUSIONS: Although
behavioral symptoms predicted depression in both caregiver groups, the
association was much stronger for daughters. This suggests that the emotional
relationship between the daughter and patient exacerbates the negative effect of
behavioral symptoms on caregiver depression. The familial relationship between
the caregiver and dementia patient should be considered in managing caregiver
stress.
PMID- 27505269
TI - Developmental and molecular biology of annelid regeneration: a comparative review
of recent studies.
AB - Studies of annelid regeneration have greatly increased in frequency in recent
years, providing new insights into the developmental basis and evolution of
regeneration. In this review, we summarize recent findings related to
regeneration in annelids, focusing on molecular and developmental studies of
epimorphic (blastema-based) regeneration, morphallactic (tissue-remodeling based)
regeneration, and development and regeneration of putative stem cells of the
posterior growth zone and germline. Regeneration is being investigated in a broad
range of annelids spanning the phylum, and comparing findings among species
reveals both widely conserved features that may be ancestral for the phylum as
well as features that are variable across the group.
PMID- 27505271
TI - Exertional Heat Illness in American Football Players: When Is the Risk Greatest?
AB - CONTEXT: Knowledge about the specific environmental and practice risks to
participants in American intercollegiate football during preseason practices is
limited. Identifying risks may mitigate occurrences of exertional heat illness
(EHI). OBJECTIVE: To evaluate the associations among preseason practice day,
session number, and wet bulb globe temperature (WBGT) and the incidence of EHI.
DESIGN: Descriptive epidemiology study. SETTING: Sixty colleges and universities
representing 5 geographic regions of the United States. PATIENTS OR OTHER
PARTICIPANTS: National Collegiate Athletic Association football players. MAIN
OUTCOME MEASURE(S): Data related to preseason practice day, session number, and
WBGT. We measured WBGT every 15 minutes during the practice sessions and used the
mean WBGT from each session in the analysis. We recorded the incidence of EHIs
and calculated the athlete-exposures (AEs). RESULTS: A total of 553 EHI cases and
365 810 AEs were reported for an overall EHI rate of 1.52/1000 AEs (95%
confidence interval [CI] = 1.42, 1.68). Approximately 74% (n = 407) of the
reported EHI cases were exertional heat cramps (incidence rate = 1.14/1000 AEs;
95% CI = 1.03, 1.25), and about 26% (n = 146) were a combination of exertional
heat syncope and heat exhaustion (incidence rate = 0.40/1000 AEs; 95% CI = 0.35,
0.48). The highest rate of EHI occurred during the first 14 days of the preseason
period, and the greatest risk was during the first 7 days. The risk of EHI
increased substantially when the WBGT was 82.0 degrees F (27.8 degrees C) or
greater. CONCLUSIONS: We found an increased rate of EHI during the first 14 days
of practice, especially during the first 7 days. When the WBGT was greater than
82.0 degrees F (27.8 degrees C), the rate of EHI increased. Sports medicine
personnel should take all necessary preventive measures to reduce the EHI risk
during the first 14 days of practice and when the environmental conditions are
greater than 82.0 degrees F (27.8 degrees C) WBGT.
PMID- 27505270
TI - Clinical and Molecular Characteristics of Neonatal Extended-Spectrum beta
Lactamase-Producing Gram-Negative Bacteremia: A 12-Year Case-Control-Control
Study of a Referral Center in Taiwan.
AB - Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative bacteremia (GNB)
in the neonatal intensive care unit was characterized by comparison with two
control groups: a susceptible control group and a general base population group
over 2001 to 2012. The influence of ESBL production on mortality was studied in
all study subjects and ESBL-GNB isolates were microbiologically characterized. We
identified 77 episodes of ESBL-GNB (14.2% of all neonatal late-onset GNB), which
were caused by Klebsiella spp. (62.3%), E. coli (20.8%) and Enterobacter spp.
(16.9%). Most ESBL-GNB strains were genetically unrelated and the SHV-type ESBLs
were the most prevalent (67% of isolates). Comparison with both control groups
disclosed previous usage of 3rd generation cephalosporin (odds ratio [OR], 4.72;
95% confidence interval [CI], 2.03-10.97; P < 0.001), and underlying renal
disease (OR, 4.07; 95% CI, 1.10-15.08; P = 0.035) as independent risk factors for
ESBL-GNB. Inadequate empiric antibiotics, a higher illness severity, higher rates
of infectious complications and sepsis-attributable mortality were more
frequently seen in neonates with ESBL-GNB than those with non-ESBL GNB (20.8% and
15.6% vs. 9.2% and 7.9%, respectively; P = 0.008 and 0.049, respectively).
Neonates with underlying secondary hypertension (OR, 7.22; 95% CI, 2.17-24.06)
and infectious complications after bacteremia (OR, 6.66; 95% CI, 1.81-19.31) were
identified as independent risk factor for in-hospital mortality. ESBL-GNB
accounted for one-seventh of all neonatal gram-negative bacteremia, especially in
neonates exposed to broad-spectrum cephalosporins. Neonates with ESBL-GNB
bacteremia more frequently received inadequate empirical antibiotic therapy,
which were associated with a higher rate of infectious complications and an
adverse outcome.
PMID- 27505272
TI - Primary Nonendoscopic Endonasal Versus Delayed External Dacryocystorhinostomy in
Acute Dacryocystitis.
AB - PURPOSE: Conventional treatment for acute dacryocystitis consists of medical
management followed by elective delayed external dacryocystorhinostomy (EXT-DCR).
The purpose of this study was to compare the outcome after primary nonendoscopic
endonasal dacryocystorhinostomy (NEN-DCR) versus conventional treatment in acute
dacryocystitis. METHODS: Retrospective chart analysis of all consecutive patients
of acute dacryocystitis presenting between 2011 and 2015 was performed. Group A
had patients who underwent primary NEN-DCR within 2 weeks of presentation. Group
B comprised age- and gender-matched patients who received conventional treatment.
RESULTS: Forty-six patients were included with 23 patients in each group. Mean
age (45.2 +/- 14.7 vs. 47.5 +/- 14 years) and gender distribution (women 17/23 in
group A vs. 15/23 in group B) in both groups were comparable. Mean duration from
presentation to surgery was 7.82 +/- 4.65 days for group A versus 27.3 +/- 12
days for group B (p = 0.00001, independent T test). Mean time for complete
resolution of symptoms was 21.4 +/- 6 days for group A versus 38.69 +/- 15.8 for
group B (p = 0.000014, independent T test). Mitomycin-C usage (0.04%; 17 vs. 14)
and mean follow up of both groups (6.4 vs. 5.7 months) were comparable. While
functional success was similar (20/23) in both, anatomical success was seen in
22/23 and 21/23 in groups A and B, respectively. Complications included
disfiguring scar in 4, recurrent acute dacryocystitis in 3, and punctal ectropion
in one patient in the EXT-DCR group. CONCLUSIONS: Primary NEN-DCR leads to faster
resolution facilitating earlier rehabilitation with comparable anatomical and
functional outcomes compared with conventional delayed EXT-DCR in acute
dacryocystitis.
PMID- 27505273
TI - Cyanide oxidation by singlet oxygen generated via reaction between H2O2 from
cathodic reduction and OCl(-) from anodic oxidation.
AB - Cyanide is widely present in electroplating wastewater or metallurgical
effluents. In the present study, the electrochemical destruction of cyanide with
various anode and cathode compositions under alkaline conditions was
investigated. The results indicated that the electrochemical system using RuO2/Ti
as anode and activated carbon fiber (ACF) as cathode in the presence of sodium
chloride was efficient for the cyanide removal. In this system, in situ
generation of HClO by anodic oxidation of Cl(-) at RuO2/Ti anode occurred with
the H2O2 generation by O2 reduction at ACF cathode. As confirmed by the electron
spin resonance technique, the reaction between HClO and H2O2 led to the
generation of singlet oxygen, which was responsible for the cyanide removal.
Further experiment indicated that the cyanide removal efficiency increased with
the increase of the current density or the sodium chloride concentration. Cyanate
was identified as main product in the system. Besides, the system exhibited good
stability for the cyanide removal, which was beneficial to its practical
application.
PMID- 27505274
TI - Investigation of metal ion interaction with a lipid cubic phase using
electrochemical impedance spectroscopy.
AB - HYPOTHESIS: Electrochemical impedance spectroscopy, EIS, can be used as a
complementary technique to investigate ion interaction with the headgroup region
in the aqueous channels of a lipid cubic phase, LCP. EXPERIMENTS: A freestanding
membrane made of monoolein LCP was formed by filling a small aperture that
separates two cell compartments. The cell compartments were filled with
electrolyte solutions at two different ionic strengths: i.e.: 10 and 100mM, of
KCl, CsBr and CaCl2. Electrochemical impedance spectroscopy was recorded between
two platinum electrodes that were present at each side of the membrane. FINDINGS:
The membrane resistance and capacitance were estimated from equivalent circuit
fitting of the impedance data. It was confirmed that calcium ions interacts
strongly with the headgroup region in the aqueous channels giving significantly
higher membrane resistances compared to monovalent alkali metal ions. The
membrane capacitance with Ca(2+)(aq) in solution was concentration dependent,
which for the first time indicates formation of two different cubic phases at
these conditions.
PMID- 27505275
TI - CdS-graphene Nanocomposite for Efficient Visible-light-driven Photocatalytic and
Photoelectrochemical Applications.
AB - This paper reports cadmium sulphide nanoparticles-(CdS NPs)-graphene
nanocomposite (CdS-Graphene), prepared by a simple method, in which CdS NPs were
anchored/decorated successfully onto graphene sheets. The as-synthesized
nanocomposite was characterized using standard characterization techniques. A
combination of CdS NPs with the optimal amount of two-dimensional graphene sheets
had a profound influence on the properties of the resulting hybrid nanocomposite,
such as enhanced optical, photocatalytic, and photo-electronic properties. The
photocatalytic degradation ability of the CdS-Graphene nanocomposite was
evaluated by degrading different types of dyes in the dark and under visible
light irradiation. Furthermore, the photoelectrode performance of the
nanocomposite was evaluated by different electrochemical techniques. The results
showed that the CdS-Graphene nanocomposite can serve as an efficient visible
light-driven photocatalyst as well as photoelectrochemical performance for
optoelectronic applications. The significantly enhanced photocatalytic and
photoelectrochemical performance of the CdS-Graphene nanocomposite was attributed
to the synergistic effects of the enhanced light absorption behaviour and high
electron conductivity of the CdS NPs and graphene sheets, which facilitates
charge separation and lengthens the lifetime of photogenerated electron-hole
pairs by reducing the recombination rate. The as-synthesized narrow band gap CdS
Graphene nanocomposite can be used for wide range of visible light-induced
photocatalytic and photoelectrochemical based applications.
PMID- 27505276
TI - Ionosilicas as efficient sorbents for anionic contaminants: Radiolytic stability
and ion capacity.
AB - Ammonium based hybrid ionosilicas were prepared from tetrasilylated ammonium
precursors. The formed material exhibited high specific surface area together
with mesoporosity. Our results indicate that ionosilicas display high exchange
capacity for iodide. They were submitted to 10MeV electron irradiation at a total
dose of 1.7MGy. Irradiation was shown not to alter the properties of ionosilica:
the morphological, textural and surface properties of the material are hardly
modified. The sorption properties (sorption capacity and cumulative displacement
enthalpy) are similar before and after electron irradiation. This high
radiolytical stability confirms that these innovative materials have therefore
high potential as anion traps for future applications in decontamination
processes or long term storage of radioactive waste.
PMID- 27505277
TI - Bioinspired polydopamine particles-assisted construction of superhydrophobic
surfaces for oil/water separation.
AB - Frequent oil spillages and industrial discharge of oils/organic solvents have
induced severe environmental pollution and ecological damage, and a great cost in
energy and finance has been consumed to solve the problems raised. Therefore, it
is urgent to develop a surface hydrophobic modification that can be applied to
materials with desired properties of high separation efficiency, excellent
selectivity and stable performance in extreme conditions during the oil/water
separation. Herein, with combined bioinspirations from mussel adhesive protein
(polydopamine) and superhydrophobic lotus leaf (hierarchical structures), we
develop a general way to superhydrophobically modify various commercial
materials, aiming for the selective removal of oils/organic solvents from water.
In this procedure, immersing commercial materials (e.g. melamine sponge,
stainless steel mesh, nylon netting and cotton cloth) into water/ethanol/ammonia
mixtures at a low concentration of dopamine (DA, 2mg/mL) allows a polydopamine
(PDA) coating with a tunable roughness appearing on the substrate in one step.
This is because DA can self-polymerize and form PDA particles with a catalyst of
ammonia, attaching to any surfaces due to abundant catechol and amine groups in
PDA, and ultimately, resulting in hierarchical structures. The subsequent
decoration with 1H, 1H, 2H, 2H-perfluorodecanethiol features the surface
superhydrophobic and superoleophilic. This approach is straightforward and
economic, and carried out under a mild, environmental-benign circumstance, with
nonspecific substrate demands. In addition, the as-prepared superhydrophobic
materials exhibit excellent separation performances including high
absorption/separation capacity, excellent selectivity, and extraordinary
recyclability for collecting various oils/organic solvents from water. These
superhydrophobic materials have also verified to be highly chemical resistant,
environment stable and mechanically durable. Therefore, this simplicity and
versatility of the direct mussel-inspired approach may facilitate the fast
development of oil/water separation materials for applications in the field of
water remediation, clean-up of oil spills and oil recovery.
PMID- 27505278
TI - Au nanorods modulated NIR fluorescence and singlet oxygen generation of water
soluble dendritic zinc phthalocyanine.
AB - A novel cyano-terminated zinc phthalocyanine (ZnPc-CN) exhibiting visible near
infrared (vis-NIR) emitting around 690nm in N,N-dimethylformamide (DMF) solvent
has been synthesized. Furthermore, the peripheral cyano groups of newly
synthesized zinc phthalocyanine were hydrolyzed in strong basic solution, leading
to water soluble carboxylated zinc phthalocyanine (ZnPc-COOH) with completely
quenched fluorescence in aqueous solution. Interestingly, we found that the NIR
fluorescence of aqueous ZnPc-COOH was dramatically recovered in the presence of
gold nanorods (Au NR), which was due to the alternation of ZnPc-COOH molecules
self-assembling via electrostatic interaction between cetyltrimethylammonium
bromide (CTAB) on the surface of Au NR and peripheral carboxyl of ZnPc-COOH. In
addition, ZnPc-COOH/Au NR conjugates demonstrated an improved singlet oxygen
generation, which could be served as potential bioimaging probe and
photosensitizer for photodynamic therapy.
PMID- 27505280
TI - High-throughput microsatellite genotyping in ecology: improved accuracy,
efficiency, standardization and success with low-quantity and degraded DNA.
AB - Microsatellite markers have played a major role in ecological, evolutionary and
conservation research during the past 20 years. However, technical constrains
related to the use of capillary electrophoresis and a recent technological
revolution that has impacted other marker types have brought to question the
continued use of microsatellites for certain applications. We present a study for
improving microsatellite genotyping in ecology using high-throughput sequencing
(HTS). This approach entails selection of short markers suitable for HTS,
sequencing PCR-amplified microsatellites on an Illumina platform and
bioinformatic treatment of the sequence data to obtain multilocus genotypes. It
takes advantage of the fact that HTS gives direct access to microsatellite
sequences, allowing unambiguous allele identification and enabling automation of
the genotyping process through bioinformatics. In addition, the massive parallel
sequencing abilities expand the information content of single experimental runs
far beyond capillary electrophoresis. We illustrated the method by genotyping
brown bear samples amplified with a multiplex PCR of 13 new microsatellite
markers and a sex marker. HTS of microsatellites provided accurate individual
identification and parentage assignment and resulted in a significant improvement
of genotyping success (84%) of faecal degraded DNA and costs reduction compared
to capillary electrophoresis. The HTS approach holds vast potential for improving
success, accuracy, efficiency and standardization of microsatellite genotyping in
ecological and conservation applications, especially those that rely on profiling
of low-quantity/quality DNA and on the construction of genetic databases. We
discuss and give perspectives for the implementation of the method in the light
of the challenges encountered in wildlife studies.
PMID- 27505279
TI - Monitoring of freshwater toxins in European environmental waters by using novel
multi-detection methods.
AB - Monitoring the quality of freshwater is an important issue for public health. In
the context of the European project MUAqua, 150 samples were collected from
several waters in France, Germany, Ireland, Italy, and Turkey for 2 yr. These
samples were analyzed using 2 multitoxin detection methods previously developed:
a microsphere-based method coupled to flow-cytometry, and an ultra-performance
liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The presence
of microcystins, nodularin, domoic acid, cylindrospermopsin, and several
analogues of anatoxin-a (ATX-a) was monitored. No traces of cylindrospermopsin or
domoic acid were found in any of the environmental samples. Microcystin-LR and
microcystin-RR were detected in 2 samples from Turkey and Germany. In the case of
ATX-a derivatives, 75% of samples contained mainly H2 -ATX-a and small amounts of
H2 -homoanatoxin-a, whereas ATX-a and homoanatoxin-a were found in only 1 sample.
These results confirm the presence and wide distribution of dihydro derivatives
of ATX-a toxins in European freshwaters. Environ Toxicol Chem 2017;36:645-654.
(c) 2016 SETAC.
PMID- 27505281
TI - Molecular epidemiology of enterovirus and parechovirus infections according to
patient age over a 4-year period in Spain.
AB - The epidemiology and clinical association of enterovirus (EV) and parechovirus
(HPeV) infections, as well as the type-distribution-according-to-age, were
determined during a 4-year study period in Spain. During 2010-2013, a total of
21,832 clinical samples were screened for EV and the detection frequency was 6.5%
(1,430). Of the total EV-negative samples, only 1,873 samples from 2011 to 2013
were available for HPeV testing. HPeV was detected in 42 (2%) of them. Positive
samples were genotyped using PCR and sequencing. EV infections occurred in all
age groups of patients: neonates (17%), children 28 days to 2 years (29%),
children 2-14 years (40%), and adults (14%). Thirty-four different EV types were
identified. HPeV infections were detected exclusively in infants <8 m (70%
neonates, P < 0.05). All but one HPeV were HPeV-3. Differences in type frequency
detection were found according to age and clinical manifestation. Coxsackievirus
(CV)-B4 (61%), CV-B5 (83%), and HPeV-3 (64%) were more frequent in neonates than
in older patients (P < 0.05). Echovirus (E)-3 (60%), E-18 (47%), E-25 (62%), CV
A6 (61%), CV-A16 (72%), and EV-71 (75%) were mainly detected in children 28 days
to 2 years (P < 0.05), whereas, E-6 (79%), E-20 (88%), and E-30 (85%) were
predominant in children >2 years and adults (P < 0.05). Clinically, meningitis
was associated with EV (P < 0.01) whereas, encephalitis was more frequent in HPeV
infected patients. CV-B types were associated with myocarditis (90%; P < 0.05)
and EV species A with hand-foot-mouth-disease/atypical exanthema (88%; P < 0.05).
J. Med. Virol. 89:435-442, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27505282
TI - How do depressive symptoms in husbands and wives relate to the interpersonal
dynamics of marital interactions?
AB - We investigated how depressive symptoms in husbands and wives may affect patterns
of interpersonal behavior during marital conflict discussions. Using the
Continuous Assessment of Interpersonal Dynamics (CAID) approach, observers rated
moment-to-moment levels of dominance and affiliation for each partner, from which
dynamic indices were derived, including the slopes for each partner and the
degree of rhythmic entrainment between partners. Results supported predictions
that the wife's depressive symptoms would be related to alterations in the
dynamics of dominance, whereas the husband's depressive symptoms would be related
to alterations in the dynamics of affiliation. For example, the higher the
husband's depressive symptoms, the less affiliative both the wife and husband
became over the interaction and the less entrained the partners were on
affiliation. The results shed new light on gender differences in the impact of
depressive symptoms on the management of marital disagreements. (PsycINFO
Database Record
PMID- 27505283
TI - Vocational interests in the United States: Sex, age, ethnicity, and year effects.
AB - Vocational interests predict educational and career choices, job performance, and
career success (Rounds & Su, 2014). Although sex differences in vocational
interests have long been observed (Thorndike, 1911), an appropriate overall
measure has been lacking from the literature. Using a cross-sectional sample of
United States residents aged 14 to 63 who completed the Strong Interest Inventory
assessment between 2005 and 2014 (N = 1,283,110), I examined sex, age, ethnicity,
and year effects on work related interest levels using both multivariate and
univariate effect size estimates of individual dimensions (Holland's Realistic,
Investigative, Artistic, Social, Enterprising, and Conventional). Men scored
higher on Realistic (d = -1.14), Investigative (d = -.32), Enterprising (d =
.22), and Conventional (d = -.23), while women scored higher on Artistic (d =
.19) and Social (d = .38), mostly replicating previous univariate findings.
Multivariate, overall sex differences were very large (disattenuated Mahalanobis'
D = 1.61; 27% overlap). Interest levels were slightly lower and overall sex
differences larger in younger samples. Overall sex differences have narrowed
slightly for 18-22 year-olds in more recent samples. Generally very small
ethnicity effects included relatively higher Investigative and Enterprising
scores for Asians, Indians, and Middle Easterners, lower Realistic scores for
Blacks and Native Americans, higher Realistic, Artistic, and Social scores for
Pacific Islanders, and lower Conventional scores for Whites. Using Prediger's
(1982) model, women were more interested in people (d = 1.01) and ideas (d =
.18), while men were more interested in things and data. These results,
consistent with previous reviews showing large sex differences and small year
effects, suggest that large sex differences in work related interests will
continue to be observed for decades. (PsycINFO Database Record
PMID- 27505284
TI - The influence of multiple oppressions on women of color's experiences with
insidious trauma.
AB - In this study, we examined the relations between multiple forms of oppressive
experiences (i.e., racism, sexism, and sexual objectification) and trauma
symptoms among Women of Color (WOC). In addition, self-esteem was explored as a
partial mediating variable in these links, and ethnic identity strength was
proposed to buffer the negative relationship between multiple forms of oppression
and self-esteem, and the positive relationship between oppressive experiences and
trauma symptoms. Results suggested that self-esteem partially mediated the
positive relationship between racist experiences and trauma symptoms, such that
racism was related to lower self-esteem, which was then related to more trauma
symptoms. Sexism and sexual objectification were directly linked with trauma
symptoms. Moreover, average and high levels of ethnic identity strength buffered
the positive link between racism and trauma symptoms. Consistent with an additive
intersectionality framework, results demonstrate the importance of attending to
multiple forms of oppression as they relate to trauma symptoms among WOC.
(PsycINFO Database Record
PMID- 27505285
TI - Confirmatory factor analytic investigation of variance composition, gender
invariance, and validity of the Male Role Norms Inventory-Adolescent-revised
(MRNI-A-r).
AB - Confirmatory factor analysis of responses to the Male Role Norms Inventory
Adolescent-revised (MRNI-A-r) from 384 middle school students (163 boys, 221
girls) indicated that the best fit to the data was a bifactor model incorporating
the hypothesized 3-factor structure while explicitly modeling an additional,
general factor. Specifically, each item-level indicator loaded simultaneously on
2 factors: a general traditional masculinity ideology factor and a specific
factor corresponding to 1 of the 3 hypothesized masculine norms for adolescents:
Emotionally Detached Dominance, Toughness, and Avoidance of Femininity.
Invariance testing across gender supported metric invariance for the general
factor only. Although item loadings on the general factor were similar across
boys and girls, the specific factor loadings varied substantially, with many
becoming nonsignificant in the presence of the general factor for girls. A
structural regression analysis predicting latent variables of the Meanings of
Adolescent Masculinity Scale (MAMS), the Rosenberg Self-esteem Scale, and the
Discipline, School Difficulties, and Positive Behavior Scale (DSDPBS) indicated
that the general factor was a strong predictor of MAMS for both genders and
DSDPBS for girls. Findings indicate that the MRNI-A-r general factor is a valid
and reliable indicator of overall internalization of traditional masculinity
ideology in adolescents; however, the specific factors may have different
meanings for boys as compared with girls and lack validity in the presence of the
general factor. These findings are consistent with a developmental perspective of
gender ideology that views adolescence as a time when a differentiated cognitive
schema of masculine norms is beginning to develop. (PsycINFO Database Record
PMID- 27505286
TI - Mode-Specific SN2 Reaction Dynamics.
AB - Despite its importance in chemistry, the microscopic dynamics of bimolecular
nucleophilic substitution (SN2) reactions is still not completely elucidated. In
this publication, the dynamics of a prototypical SN2 reaction (F(-) + CH3Cl ->
CH3F + Cl(-)) is investigated using a high-dimensional quantum mechanical model
on an accurate potential energy surface (PES) and further analyzed by quasi
classical trajectories on the same PES. While the indirect mechanism dominates at
low collision energies, the direct mechanism makes a significant contribution.
The reactivity is found to depend on the specific reactant vibrational mode
excitation. The mode specificity, which is more prevalent in the direct reaction,
is rationalized by a transition-state-based model.
PMID- 27505287
TI - Registered Nurses' Perceptions about the Situation of Family Caregivers to
Patients with Heart Failure - A Focus Group Interview Study.
AB - INTRODUCTION: Heart failure is a growing public health problem associated with
poor quality of life and significant morbidity and mortality. The majority of
heart failure care is provided by family caregivers, and is associated with
caregiver burden and reduced quality of life. Research emphasizes that future
nursing interventions should recognize the importance of involving family
caregivers to achieve optimal outcomes. AIMS: The aims of this study are to
explore registered nurses' perceptions about the situation of family caregivers
to patients with heart failure, and registered nurses' interventions, in order to
improve family caregivers' situation. METHODS: The study has a qualitative design
with an inductive approach. Six focus group interviews were held with 23
registered nurses in three hospitals and three primary health care centres. Data
were analysed using qualitative content analysis. RESULTS: Two content areas were
identified by the a priori study aims. Four categories and nine sub-categories
emerged in the analysis process. The content area "Family caregivers' situation"
includes two categories: "To be unburdened" and "To comprehend the heart failure
condition and its consequences". The content area "Interventions to improve
family caregivers' situation" includes two categories: "Individualized support
and information" and "Bridging contact". CONCLUSIONS: Registered nurses perceive
family caregivers' situation as burdensome, characterized by worry and
uncertainty. In the PHCCs, the continuity and security of an RN as a permanent
health care contact was considered an important and sustainable intervention to
better care for family caregivers' worry and uncertainty. In the nurse-led heart
failure clinics in hospitals, registered nurses can provide family caregivers
with the opportunity of involvement in their relative's health care and address
congruence and relationship quality within the family through the use of "Shared
care" and or Family-centred care. Registered nurses consider it necessary to have
a coordinated individual care plan as a basis for collaboration between the
county council and the municipality.
PMID- 27505288
TI - Joint toxicity prediction of nanoparticles and ionic counterparts: Simulating
toxicity under a fate scenario.
AB - The joint effects of NPs with other chemicals is not fully yet understood along
with the joint effects of the particulate and dissolved forms/fractions. The
predictability of joint effects is of great importance for environmental risk
assessment. Therefore this study aimed at inferring on the predictability of NPs
binary mixture toxicity based on their ionic counterparts' mixtures, and
evaluating if the joint toxicity of two forms of the same element (NP and ion)
acts as dilution of each other. Effects of individual and mixtures of ZnO and Ag
NPs and their respective salts (AgNO3 and ZnCl2) were studied in immobilization
and feeding tests using Daphnia magna. NPs mixture toxicity patterns did not
mirror their ionic counterparts' mixture toxicity responses and therefore their
prediction should not rely on the available knowledge for regular chemicals.
Regarding mixtures from the same element with different forms (NP and ions), both
Zn and Ag mixtures showed a deviation from additivity, relying on the interaction
between NP and ions. A synergistic effect was depicted when the concentrations of
Ag ions increased, while antagonism was observed with AgNP increase in
suspension. This is an expected pattern in long term studies due to dissolution,
relating fate and toxicity.
PMID- 27505289
TI - Prevalence and dissemination of antibiotic resistance genes and coselection of
heavy metals in Chinese dairy farms.
AB - This study aims to explore prevalence and dissemination of antibiotic resistance
genes (ARGs) in dairy farms. A variety of ARGs conferring resistance to most
classes of antibiotics were detected in feces and soil samples obtained from
dairy farms, using a high-throughput metagenomic sequencing approach. The ARGs
observed in the feces and the soil samples were significantly correlated
(p<0.01). The abundance of mobile genetics elements, such as transposase, was
also examined to evaluate the potential risk of horizontal ARGs transfer. The
positive correlation (p<0.001) between the total abundance of transposase genes
and ARGs in the soil samples suggested strong dissemination capacity of ARGs in
soil. In addition, the ARGs and metal resistance genes (MRGs) were significantly
correlated with heavy metals in the feces (p<0.01), suggesting that the heavy
metals promoted the emergence of metal resistance, and participated in the
coselection processes for ARGs. The prevalence of ARGs with high levels of
genetic mobile elements in the dairy farms suggests that cattle excrement is a
major reservoir of ARGs with a high risk of dissemination, which increases the
potential risk of environmental pollution and threatens public health.
PMID- 27505290
TI - Experimental investigation of spontaneous ignition and flame propagation at
pressurized hydrogen release through tubes with varying cross-section.
AB - An experimental investigation of spontaneous ignition and flame propagation at
high-pressure hydrogen release via cylindrical tubes with varying cross-section
is presented. Tubes with different transverse cross-sections are considered in
the experiments: (1) local contraction, (2) local enlargement, (3) abrupt
contraction, and (4) abrupt enlargement. The results show that the presence of
the varying cross-section geometries can significantly promote the occurrence of
spontaneous ignition. Compared to the tube with constant cross-section, the
minimum pressure release needed for spontaneous ignition for the varying cross
sections tubes is considerably lower. Moreover, the initial ignition location is
closer to the disk in the presence of varying cross-section geometries in
comparison with straight channel. As the flame emerges from the outlet of the
tube, the velocity of the flame front in the vicinity of the nozzle increases
sharply. Then, a deflagration develops across the mixing zone of hydrogen/air
mixture. The maximum deflagration overpressure increases linearly with the
release pressure. Subsequently, a hydrogen jet flame is produced and evolves
different shapes at different release stages. A fireball is formed after the jet
flame spouts in the open air. Later, the fireball develops into a jet flame which
shifts upward and continues to burn in the vertical direction.
PMID- 27505291
TI - Iron phthalocyanine supported on amidoximated PAN fiber as effective catalyst for
controllable hydrogen peroxide activation in oxidizing organic dyes.
AB - Iron(II) phthalocyanine was immobilized onto amidoximated polyacrylonitrile fiber
to construct a bioinspired catalytic system for oxidizing organic dyes by H2O2
activation. The amidoxime groups greatly helped to anchor Iron(II) phthalocyanine
molecules onto the fiber through coordination interaction, which has been
confirmed by Fourier transform infrared spectroscopy, X-ray photoelectron
spectroscopy and UV-vis diffuse reflectance spectroscopy analyses. Electron spin
resonance studies indicate that the catalytic process of physically anchored
Iron(II) phthalocyanine performed via a hydroxyl radical pathway, while the
catalyst bonded Iron(II) phthalocyanine through coordination effect could
selectively catalyze the H2O2 decomposition to generate high-valent iron-oxo
species. This may result from the amidoxime groups functioning as the axial fifth
ligands to favor the heterolytic cleavage of the peroxide OO bond. This feature
also enables the catalyst to only degrade the dyes adjacent to the catalytic
active centers and enhances the efficient utilization of H2O2. In addition, this
catalyst could effectively catalyze the mineralization of organic dyes and can be
easily recycled without any loss of activity.
PMID- 27505292
TI - Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective
Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment.
AB - Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying
clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be
asymptomatic or else present with recurrent infection, autoimmunity, atopic
disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have
impaired antibody responses to the pneumococcal polysaccharide vaccine. We report
on an adult who presented with symptomatic SIgMD with impaired pneumococcal
polysaccharide antibody responses and lymphopenia, who experienced a significant
clinical improvement in the frequency of infections after subcutaneous
immunoglobulin replacement therapy.
PMID- 27505293
TI - Anti-Viral Therapy and Decreased Sexual Desire in Patients with Chronic Hepatitis
C.
AB - PURPOSE: Peg-interferon (PegIFN)alpha2a or PegIFNalpha2b plus ribavirin (RBV) is
the standard therapy for chronic hepatitis C virus (HCV) infection in Taiwan and
Asia. It is commonly associated with adverse effects, but the issue of sexual and
mental health is not well reported. This study aimed to evaluate the impact of
anti-viral therapy with PegIFNalpha plus RBV on sexual desire and depression.
METHODS: This prospective cohort study from 2009 to 2014 enrolled 181 patients
with HCV who received PegIFNalpha2a (180 mcg/week) or PegIFNalpha2b (1.5
mcg/Kg/week) plus RBV (800-1200 mg/day) according to response-guide therapy for
24 to 48 weeks in a tertiary medical center. Patients with decreased sexual
desire (DSD) before PegIFNalpha plus RBV were excluded. Patients were evaluated
at baseline (week 0) and after 2, 4, 8, 12, 16, 20, and 24 weeks of PegIFNalpha
plus RBV treatment using the structured Mini-International Neuropsychiatric
Interview, for the diagnosis of a major depressive episode, and the 21-item Beck
Depression Inventory (BDI), for monitoring depressive symptoms. The 21st item of
the BDI was used to evaluate DSD. RESULTS: During therapy, 124 (68.5%) patients
had DSD. The BDI score peaked at 14.8 weeks. The severity of DSD was greatest at
16 weeks of treatment. The average score of the 21st item of the BDI correlated
with DSD. Depression history and the prevalence of subsequent major depressive
disorder after anti-viral therapy was correlated to DSD (p = 0.05 and 0.001).
Male patients complained of DSD more significantly than females (p = 0.031).
CONCLUSIONS: Decreased sexual desire is common but is usually neglected in
patients with chronic hepatitis C undergoing anti-viral therapy, especially among
male patients. Physicians must be monitoring the side effects of sexual health
and depression.
PMID- 27505294
TI - Fit for purpose application of currently existing animal models in the discovery
of novel epilepsy therapies.
AB - Animal seizure and epilepsy models continue to play an important role in the
early discovery of new therapies for the symptomatic treatment of epilepsy. Since
1937, with the discovery of phenytoin, almost all anti-seizure drugs (ASDs) have
been identified by their effects in animal models, and millions of patients world
wide have benefited from the successful translation of animal data into the
clinic. However, several unmet clinical needs remain, including resistance to
ASDs in about 30% of patients with epilepsy, adverse effects of ASDs that can
reduce quality of life, and the lack of treatments that can prevent development
of epilepsy in patients at risk following brain injury. The aim of this review is
to critically discuss the translational value of currently used animal models of
seizures and epilepsy, particularly what animal models can tell us about epilepsy
therapies in patients and which limitations exist. Principles of translational
medicine will be used for this discussion. An essential requirement for
translational medicine to improve success in drug development is the availability
of animal models with high predictive validity for a therapeutic drug response.
For this requirement, the model, by definition, does not need to be a perfect
replication of the clinical condition, but it is important that the validation
provided for a given model is fit for purpose. The present review should guide
researchers in both academia and industry what can and cannot be expected from
animal models in preclinical development of epilepsy therapies, which models are
best suited for which purpose, and for which aspects suitable models are as yet
not available. Overall further development is needed to improve and validate
animal models for the diverse areas in epilepsy research where suitable fit for
purpose models are urgently needed in the search for more effective treatments.
PMID- 27505295
TI - Nature and incidence of severe limbal stem cell deficiency in Australia and New
Zealand.
AB - BACKGROUND: This study aimed to determine the nature and incidence of severe
limbal stem cell deficiency (LSCD) in Australia and New Zealand. DESIGN: A 1-year
pilot surveillance study with a 1-year follow-up period was conducted in
association with the Australian and New Zealand Ophthalmic Surveillance Unit.
PARTICIPANTS: The study included patients reported by practising ophthalmologists
on the Surveillance Unit's database. METHODS: Ophthalmologists were provided with
a definition of severe limbal stem cell deficiency, contacted on a monthly basis
by the Unit and asked to report newly diagnosed cases. MAIN OUTCOME MEASURES:
Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy,
an opaque epithelium arising from the limbus, late fluorescein staining of the
involved epithelium and superficial corneal neovascularization or
conjunctivalization. RESULTS: On average, 286 report cards were sent by the
Surveillance Unit to practising ophthalmologists each month (total 3429 over 12
months) and the Unit received an average of 176 responses per month (total 2111;
62% response rate). During the 1-year study period from April 2013 to March 2014,
14 positive cases were reported to the Unit. A range of underlying aetiologies
were implicated, with contact lens over-wear and cicatrizing conjunctivitis being
the most common (n = 3). CONCLUSIONS: This surveillance study is the first
worldwide to document the incidence of limbal stem cell deficiency; however,
because of study design limitations, it is likely to have been under-reported. It
provides novel data on the demographics, clinical conditions and management of
patients with limbal stem cell deficiency as reported by treating
ophthalmologists.
PMID- 27505296
TI - 2016 European guideline on Mycoplasma genitalium infections.
AB - Mycoplasma genitalium infection contributes to 10-35% of non-chlamydial non
gonococcal urethritis in men. In women, M. genitalium is associated with
cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium
occurs through direct mucosal contact. Asymptomatic infections are frequent. In
women, symptoms include vaginal discharge, dysuria or symptoms of PID - abdominal
pain and dyspareunia. In men, urethritis, dysuria and discharge predominates.
Besides symptoms, indication for laboratory test is a high-risk sexual behaviour.
Diagnosis is achievable only through nucleic acid amplification testing (NAAT).
If available, NAAT diagnosis should be followed with an assay for macrolide
resistance. Therapy for M. genitalium is indicated if M. genitalium is detected
or on an epidemiological basis. Doxycycline has a low cure rate of 30-40%, but
does not increase resistance. Azithromycin has a cure rate of 85-95% in macrolide
susceptible infections. An extended course appears to have a higher cure rate. An
increasing prevalence of macrolide resistance, most likely due to widespread use
of azithromycin 1 g single dose without test of cure, is drastically decreasing
the cure rate. Moxifloxacin can be used as second-line therapy, but resistance is
increasing. Uncomplicated M. genitalium infection should be treated with
azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral), or josamycin 500
mg three times daily for 10 days (oral). Second line treatment and treatment for
uncomplicated macrolide resistant M. genitalium infection is moxifloxacin 400 mg
od for 7-10 days (oral). For third line treatment of persistent M. genitalium
infection after azithromycin and moxifloxacin doxycycline 100 mg two times daily
for 14 days can be tried and may cure 30%. Pristinamycin 1 g four times daily for
10 days (oral) has a cure rate of app. 90%. Complicated M. genitalium infection
(PID, epididymitis) is treated with moxifloxacin 400 mg od for 14 days.
PMID- 27505297
TI - Misdiagnosis of asthma in schoolchildren.
AB - BACKGROUND: A correct diagnosis of asthma is the cornerstone of asthma
management. Few pediatric studies have examined the accuracy of physician
diagnosed asthma. OBJECTIVES: We determined the accuracy of parent reported
physician-diagnosed asthma in children sampled from a community cohort. METHODS:
Nested case-control study that recruited 203 children, aged 9-12, from a
community-based sample. Three groups were recruited: asthma cases had a parental
report of physician-diagnosed asthma, symptomatic controls had respiratory
symptoms without a diagnosis of asthma, and asymptomatic controls had no
respiratory symptoms. All participants were assessed and assigned a clinical
diagnosis by one of three study physicians, and then completed spirometry,
methacholine challenge, and allergy skin testing. The reference standard of
asthma required a study physician's clinical diagnosis of asthma and either
reversible bronchoconstriction or a positive methacholine challenge. Diagnostic
accuracy, sensitivity and specificity were calculated for parent-reported asthma
diagnosis compared to the reference standard. RESULTS: One hundred two asthma
cases, 52 controls with respiratory symptoms but no asthma diagnosis, and 49
asymptomatic controls were assessed. Physician agreement for the diagnosis of
asthma was moderate (kappa 0.46-0.81). Compared to the reference standard, 45% of
asthma cases were overdiagnosed and 10% of symptomatic controls were
underdiagnosed. Parental report of physician-diagnosed asthma had 75% sensitivity
and 92% specificity for correctly identifying asthma. CONCLUSIONS: There is
significant misclassification of childhood asthma when the diagnosis relies
solely on a clinical history. This study highlights the importance of objective
testing to confirm the diagnosis of asthma. Pediatr Pulmonol. 2017;52:293-302.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27505298
TI - Solution Binding and Structural Analyses Reveal Potential Multidrug Resistance
Functions for SAV2435 and CTR107 and Other GyrI-like Proteins.
AB - Multidrug resistance (MDR) refers to the acquired ability of cells to tolerate a
broad range of toxic compounds. One mechanism cells employ is to increase the
level of expression of efflux pumps for the expulsion of xenobiotics. A key
feature uniting efflux-related mechanisms is multidrug (MD) recognition, either
by efflux pumps themselves or by their transcriptional regulators. However,
models describing MD binding by MDR effectors are incomplete, underscoring the
importance of studies focused on the recognition elements and key motifs that
dictate polyspecific binding. One such motif is the GyrI-like domain, which is
found in several MDR proteins and is postulated to have been adapted for small
molecule binding and signaling. Here we report the solution binding properties
and crystal structures of two proteins containing GyrI-like domains, SAV2435 and
CTR107, bound to various ligands. Furthermore, we provide a comparison with
deposited crystal structures of GyrI-like proteins, revealing key features of
GyrI-like domains that not only support polyspecific binding but also are
conserved among GyrI-like domains. Together, our studies suggest that GyrI-like
domains perform evolutionarily conserved functions connected to multidrug binding
and highlight the utility of these types of studies for elucidating mechanisms of
MDR.
PMID- 27505299
TI - Synthetic Utilization of alpha-Aminoalkyl Radicals and Related Species in Visible
Light Photoredox Catalysis.
AB - Single electron oxidation of amines provides an efficient way to access
synthetically useful alpha-aminoalkyl radicals as reactive intermediates. After
the single electron oxidation of amines, fragmentation of the resulting radical
cations proceeds to give the alpha-aminoalkyl radicals along with generation of a
proton. In the synthetic utilization of the alpha-aminoalkyl radicals, precise
control of single electron transfer is essential, because further oxidation of
the alpha-aminoalkyl radicals occurs more easily than the starting amines and the
alpha-aminoalkyl radicals are converted into the corresponding iminium ions. As a
result, photoinduced single electron transfer is quite attractive in the
synthetic utilization of the alpha-aminoalkyl radicals. Recently, visible light
photoredox catalysis using transition metal-polypyridyl complexes and other dyes
as catalysts has attracted considerable attention, where useful molecular
transformations can be achieved through the single electron transfer process
between the excited catalysts and substrates. In this context, MacMillan et al. (
Science 2011, 334 , 1114 , DOI: 10.1126/science.1213920 ) reported an aromatic
substitution reaction of cyanoarenes with amines, where alpha-aminoalkyl radicals
work as key reactive intermediates. Pandey and Reiser et al. ( Org. Lett. 2012 ,
14 , 672 , DOI: 10.1021/ol202857t ) and our group ( Nishibayashi et al. J. Am.
Chem. Soc. 2012 , 134 , 3338 , DOI: 10.1021/ja211770y ) independently reported
reactions of amines with alpha,beta-unsaturated carbonyl compounds, where
addition of alpha-aminoalkyl radicals to alkenes is a key step. After these
earliest examples, nowadays, a variety of transformations using the alpha
aminoalkyl radicals as reactive intermediates have been reported by many groups.
The alpha-aminoalkyl radicals are usually produced from amines by single electron
oxidation and the subsequent deprotonation of the C-H bond adjacent to the
nitrogen atom. In addition, the alpha-aminoalkyl radicals are also produced from
alpha-silylamines and alpha-amino acids in high efficiency through desilylation
or decarboxylation after the single electron oxidation. The generated alpha
aminoalkyl radicals are utilized in a variety of reaction systems. In fact,
reactions based on the addition of alpha-aminoalkyl radicals to alkenes and other
unsaturated bonds have been extensively studied. Aromatic and other types of
substitution reactions have also been investigated. Some of these transformations
are achieved by combination of photoredox catalysts and other catalysts such as
Bronsted and Lewis acids, organocatalysts, and transition metal catalysts. It is
also noteworthy that the enantioselective reactions have been accomplished by
combination of photoredox catalysts and chiral catalysts. The strategy for the
generation of alpha-aminoalkyl radicals can be applied to utilize other types of
alkyl radicals. In the generation of alpha-aminoalkyl radicals, the bond
dissociation of the radical cations occurs at the alpha-position of amines. In
relation to this process, synthetic utilization of other types of alkyl radicals
generated by the bond dissociation of the radical cations at a remote position
has been also investigated. These alkyl radicals have been applied to molecular
transformations in a manner similar to the alpha-aminoalkyl radicals. Recently,
organic synthesis using the alpha-aminoalkyl radicals and related alkyl radicals
has been studied extensively. In this Account, we describe recent advances in
photoredox-catalyzed synthetic utilization of these alkyl radicals.
PMID- 27505300
TI - Radio-protective effect of some new curcumin analogues.
AB - In the present study, novel symmetrical curcumin analogues (2-7) have been
synthesized by substituting the phenolic OH of curcumin with different linkers
providing additional keto-enol tautomerism, very essential for radioprotective
activity. The structures of the synthesized compounds (2-7) were elucidated by
elemental analysis, IR, (1)H-NMR, (13)C-NMR and mass spectral data and were found
consistent with the assigned structures. The curative effect of these new
compounds, against the oxidative stress due to exposure of rats to the whole body
gamma-irradiation (7Gy) was investigated. Gamma-irradiated rats exhibited
elevations of ALT, AST activities, urea, creatinine, triglycerides, total
cholesterol, malondialdehyde (MDA), nitric oxide (NO), Interleukin-6 (IL-6),
Tumor Necrosis Factor-alpha (TNF-alpha) and Nuclear Factor-kappa B (NF-kappaB)
levels. Contrariwise, the total protein, albumin, total calcium level, SOD, CAT,
GSH-Px, GST activities and GSH content were decreased. Treatment of gamma
irradiated rats with the new curcumin analogues (2-7) showed significant
amelioration in the in-vivo antioxidant status, liver and kidney functions, as
well as the anti-inflammatory markers (IL-6, TNF-alpha and NF-kappaB). Inhibition
of NF-kappaB could be responsible for the improvement of the antioxidant and anti
inflammatory status in gamma-irradiated animals, by down-regulation of IL-1beta
and TNF-alpha level. In conclusion, the new curcumin analogues (2-7) exhibited
post-protective effect on gamma-irradiation, by NF-kappaB inhibition.
PMID- 27505301
TI - Randomized clinical trial comparing 10- or 14-day sequential therapy and 10- or
14-day concomitant therapy for the first line empirical treatment of Helicobacter
pylori infection.
AB - BACKGROUND AND AIM: Whether concomitant therapy is superior to sequential therapy
(ST) as first-line therapy of Helicobacter pylori in areas with high
clarithromycin resistance remains controversial. The aim of this study was to
compare the efficacy and tolerability of 10- or 14-day ST with 10- or 14-day
concomitant therapy (CT). METHODS: This was a prospective randomized study
comparing 10- or 14-day ST with 10- or 14-day CT. The ST-10 and ST-14 groups
received pantoprazole 40 mg and amoxicillin 1 g twice a day for the first 5 and 7
days followed by pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500
mg twice a day for the remaining 5 and 7 days, respectively. The CT-10 and CT-14
groups received pantoprazole 40 mg, amoxicillin 1 g, clarithromycin 500 mg, and
metronidazole 500 mg twice daily for 10 and 14 days, respectively. RESULTS: Three
hundred forty-one patients were randomly allocated to the four groups. The
modified intention-to-treat eradication rates of ST-10, ST-14, CT-10, and CT-14
were 91.7%, 91.2%, 94.2%, and 98.5%, respectively. The corresponding per protocol
eradication rates were 91.4%, 91.0%, 95.6%, and 98.5%. There was no difference in
compliance and adverse events in the four groups. Eradication rates increased
sequentially with statistical significance in the following order: ST-10, ST-14,
CT-10, and CT-14 (P = 0.044). CONCLUSIONS: All four regimens achieved eradication
rates >90% in per protocol analyses in a country with high clarithromycin
resistance. There was no difference in tolerability among the four regimens.
PMID- 27505303
TI - Synthetic Tuning of Redox, Spectroscopic, and Photophysical Properties of
{Mo6I8}(4+) Core Cluster Complexes by Terminal Carboxylate Ligands.
AB - The reactions between the tetra-n-butylammonium salt of [{Mo6I8}I6](2-) and
silver carboxylates RCOOAg (R = CH3 (1), C(CH3)3 (2), alpha-C4H3O (3), C6H5 (4),
alpha-C10H7 (5), or C2F5 (6)) in CH2Cl2 afforded new carboxylate complexes
[{Mo6I8}(RCOO)6](2-). The complexes were characterized by X-ray single-crystal
diffraction and elemental analysis, cyclic/differential pulse voltammetry, and
IR, NMR, and UV-visible spectroscopies. The emission properties of the complexes
1-6, and those of the earlier reported complexes with R = CF3 (7) and n-C3F7 (8),
were studied both in acetonitrile solution and in the solid state. In deaerated
CH3CN at 298 K, all of the complexes 1-8 exhibit intense and long-lived emission
with the quantum yield and lifetime being 0.48-0.73 and 283-359 MUs,
respectively. The oxidation (Eox)/reduction (Ered) potentials of the complexes
correlate linearly with the pKa value of the terminal carboxylate ligands L =
RCOO (pKa(L)). Reflecting the pKa(L) dependences of Eox/Ered, the emission energy
(nuem) of the complexes was also shown to correlate with pKa(L). The present
study successfully demonstrates synthetic tuning of the redox, spectroscopic, and
photophysical characteristics of a {Mo6I8}(4+)-based cluster complex with pKa(L).
PMID- 27505302
TI - Importance of the Anchor Group Position (Para versus Meta) in Tetraphenylmethane
Tripods: Synthesis and Self-Assembly Features.
AB - The efficient synthesis of tripodal platforms based on tetraphenylmethane with
three acetyl-protected thiol groups in either meta or para positions relative to
the central sp(3) carbon for deposition on Au (111) surfaces is reported. These
platforms are intended to provide a vertical arrangement of the substituent in
position 4 of the perpendicular phenyl ring and an electronic coupling to the
gold substrate. The self-assembly features of both derivatives are analyzed on Au
(111) surfaces by low-temperature ultra-high-vacuum STM, high-resolution X-ray
photoelectron spectroscopy, near-edge X-ray absorption fine structure
spectroscopy, and reductive voltammetric desorption studies. These experiments
indicated that the meta derivative forms a well-ordered monolayer, with most of
the anchoring groups bound to the surface, whereas the para derivative forms a
multilayer film with physically adsorbed adlayers on the chemisorbed para
monolayer. Single-molecule conductance values for both tripodal platforms are
obtained through an STM break junction experiment.
PMID- 27505304
TI - Paper Thermoelectrics: Merging Nanotechnology with Naturally Abundant Fibrous
Material.
AB - The development of paper-based sensors, antennas, and energy-harvesting devices
can transform the way electronic devices are manufactured and used. Herein we
describe an approach to fabricate paper thermoelectric generators for the first
time by directly impregnating naturally abundant cellulose materials with p- or n
type colloidal semiconductor quantum dots. We investigate Seebeck coefficients
and electrical conductivities as a function of temperature between 300 and 400 K
as well as in-plane thermal conductivities using Angstrom's method. We further
demonstrate equipment-free fabrication of flexible thermoelectric modules using p
and n-type paper strips. Leveraged by paper's inherently low thermal
conductivity and high flexibility, these paper modules have the potential to
efficiently utilize heat available in natural and man-made environments by
maximizing the thermal contact to heat sources of arbitrary geometry.
PMID- 27505305
TI - Effectiveness of a Predictive Algorithm in the Prevention of Exercise-Induced
Hypoglycemia in Type 1 Diabetes.
AB - BACKGROUND: Sensor-augmented pump therapy (SAPT) with a predictive algorithm to
suspend insulin delivery has the potential to reduce hypoglycemia, a known
obstacle in improving physical activity in patients with type 1 diabetes. The
predictive low glucose management (PLGM) system employs a predictive algorithm
that suspends basal insulin when hypoglycemia is predicted. The aim of this study
was to determine the efficacy of this algorithm in the prevention of exercise
induced hypoglycemia under in-clinic conditions. METHODS: This was a randomized,
controlled cross-over study in which 25 participants performed 2 consecutive
sessions of 30 min of moderate-intensity exercise while on basal continuous
subcutaneous insulin infusion on 2 study days: a control day with SAPT alone and
an intervention day with SAPT and PLGM. The predictive algorithm suspended basal
insulin when sensor glucose was predicted to be below the preset hypoglycemic
threshold in 30 min. We tested preset hypoglycemic thresholds of 70 and 80 mg/dL.
The primary outcome was the requirement for hypoglycemia treatment (symptomatic
hypoglycemia with plasma glucose <63 mg/dL or plasma glucose <50 mg/dL) and was
compared in both control and intervention arms. RESULTS: Results were analyzed in
19 participants. In the intervention arm with both thresholds, only 6
participants (32%) required treatment for hypoglycemia compared with 17
participants (89%) in the control arm (P = 0.003). In participants with a 2-h
pump suspension on intervention days, the plasma glucose was 84 +/- 12 and 99 +/-
24 mg/dL at thresholds of 70 and 80 mg/dL, respectively. CONCLUSIONS: SAPT with
PLGM reduced the need for hypoglycemia treatment after moderate-intensity
exercise in an in-clinic setting.
PMID- 27505306
TI - Barriers to and enablers of insulin self-titration in adults with Type 2
diabetes: a qualitative study.
AB - AIMS: To identify the barriers to and enablers of effective insulin self
titration in people with Type 2 diabetes. METHODS: A qualitative semi-structured
interview approach was used. Questions were structured according to the
Theoretical Domains Framework, which outlines 14 domains that can act as barriers
to and enablers of changing behaviour. Interviews were audio-recorded and
transcribed verbatim. The data were coded according to the 14 domains, belief
statements were created within each domain, and a frequency count of the most
reported barriers and enablers was then carried out. Analyses were conducted by
two researchers, and discrepancies agreed with a third researcher. RESULTS: A
total of 18 adults with Type 2 diabetes took part in an interview. The majority
were of South-Asian ethnicity (n = 8) and were men (n = 12). Their mean age was
61 years old. The mean duration of diabetes was 16 years and time on insulin 9
years. Inter-rater reliability for each of the domains varied (29-100%). The most
frequently reported domains were Social Influence and Beliefs about Consequences;
the least frequently reported were Optimism and Reinforcement. Interviewees
reported receiving support to self-titrate from a range of sources. Self
titrating was perceived to have a range of both positive and negative
consequences, as was not titrating. CONCLUSIONS: The findings highlight that
those interviewed experienced a range of barriers and enablers when attempting to
self-titrate. Improved education and training when initiating insulin treatment
among adults with Type 2 diabetes, and throughout their journey on insulin
therapy could help identify and address these barriers in order to optimize self
titration.
PMID- 27505307
TI - Oxytocin and arginine vasopressin receptor evolution: implications for adaptive
novelties in placental mammals.
AB - Oxytocin receptor (OXTR) and arginine vasopressin receptors (AVPR1a, AVPR1b, and
AVPR2) are paralogous genes that emerged through duplication events; along the
evolutionary timeline, owing to speciation, numerous orthologues emerged as well.
In order to elucidate the evolutionary forces that shaped these four genes in
placental mammals and to reveal specific aspects of their protein structures, 35
species were selected. Specifically, we investigated their molecular evolutionary
history and intrinsic protein disorder content, and identified the presence of
short linear interaction motifs. OXTR seems to be under evolutionary constraint
in placental mammals, whereas AVPR1a, AVPR1b, and AVPR2 exhibit higher
evolutionary rates, suggesting that they have been under relaxed or experienced
positive selection. In addition, we describe here, for the first time, that the
OXTR, AVPR1a, AVPR1b, and AVPR2 mammalian orthologues preserve their disorder
content, while this condition varies among the paralogues. Finally, our results
reveal the presence of short linear interaction motifs, indicating possible
functional adaptations related to physiological and/or behavioral taxa-specific
traits.
PMID- 27505309
TI - Comparison of Early Submucosal Enhancement and Tumor Stalk in Staging Bladder
Urothelial Carcinoma.
AB - OBJECTIVE: The purpose of this study was to compare the efficacy of submucosal
enhancement on dynamic contrast-enhanced MRI (DCE-MRI) and detection of a stalk
on DWI for differentiating stage T1 from stage T2 bladder urothelial carcinoma.
SUBJECTS AND METHODS: Our prospective study was approved by the institutional
medical ethics committee and informed consent was obtained from all patients.
Fifty-nine patients (92 tumors in total) with urothelial bladder cancer underwent
MRI within 2 weeks before surgery. Two image sets of T2-weighted MRI with DWI and
T2-weighted with DCE-MRI were interpreted independently at 2-week intervals by
two uroradiologists without any knowledge of the surgical or histologic findings.
The tumor was categorized as stage T1 or lower when a stalk was evident at the
tumor base on DWI or when continuous linear submucosal enhancement was detected
in the early phase of DCE-MRI. Tumors without stalks or with discontinuous linear
submucosal enhancement were categorized as stage T2. RESULTS: Of the 42 tumors
with stalks on DWI, 41 showed continuous and one had discontinuous submucosal
enhancement on DCE-MRI. In 50 carcinomas without stalks on DWI, submucosal
enhancement was absent in 34, continuous in 12, and discontinuous in four. The
staging accuracy of DWI (91.3%, 84/92) and DCE-MRI (91.3%, 84/92) was improved to
94.6% (87/92) by combining the interpretations of both DWI and DCE-MRI.
CONCLUSION: Submucosal linear enhancement under the tumor base on DCE-MRI
complements tumor stalk detection on DWI for differentiating stage T1 from stage
T2 bladder urothelial carcinoma.
PMID- 27505308
TI - Plant senescence and proteolysis: two processes with one destiny.
AB - Senescence-associated proteolysis in plants is a complex and controlled process,
essential for mobilization of nutrients from old or stressed tissues, mainly
leaves, to growing or sink organs. Protein breakdown in senescing leaves involves
many plastidial and nuclear proteases, regulators, different subcellular
locations and dynamic protein traffic to ensure the complete transformation of
proteins of high molecular weight into transportable and useful hydrolysed
products. Protease activities are strictly regulated by specific inhibitors and
through the activation of zymogens to develop their proteolytic activity at the
right place and at the proper time. All these events associated with senescence
have deep effects on the relocation of nutrients and as a consequence, on grain
quality and crop yield. Thus, it can be considered that nutrient recycling is the
common destiny of two processes, plant senescence and, proteolysis. This review
article covers the most recent findings about leaf senescence features mediated
by abiotic and biotic stresses as well as the participants and steps required in
this physiological process, paying special attention to C1A cysteine proteases,
their specific inhibitors, known as cystatins, and their potential targets,
particularly the chloroplastic proteins as source for nitrogen recycling.
PMID- 27505310
TI - Comparison of the extent and pattern of cognitive impairment among predialysis,
dialysis and transplant patients: A cross-sectional study from Australia.
AB - AIM: The aim of this study was to compare the extent of cogntive impairment and
the types of cognitive deficits in an Australian cohort of four patient groups
with end stage kidney disease. Characteristics predicting the presence of
cognitive impairment were also evaluated. METHODS: Observational cross-sectional
study of 155 patients with end stage kidney disease are recruited from a regional
Australian renal unit. Eligible participants included those whose estimated
Glomerular Filtration Rate was < 30 ml/min per 1.73 m2 , were undertaking
peritoneal or haemodialysis, or had received a kidney transplant. The Montreal
Cognitive Assessment tool was used to screen the study participants for cognitive
impairment and evaluate cognitive deficits. Cognitive impairment was defined as a
total Montreal Cognitive Assessment tool score <=24/30. RESULTS: The extent of
cognitive impairment varied between the four groups with end stage kidney
disease. Factors predicting the presence of cognitive impairment included
undertaking dialysis, age >=65, male gender and the presence of diabetes or
cerebrovascular disease. Deficits in executive function, attention, language,
visuospatial skills, memory and orientation were common among the study
participants, and the extent of these deficits varied between groups. Limitations
to the study included the cross-sectional design, and that the presence of
confounders like depression were not recorded. CONCLUSION: The impact of
disparities in the cognitive capabilities identified in this study are likely to
be far reaching. Tailoring of education and self-management programmes to the
cognitive deficits of individuals is required.
PMID- 27505311
TI - Combining Placido and Corneal Wavefront Data for the Detection of Forme Fruste
Keratoconus.
AB - PURPOSE: To evaluate the accuracy of a new objective method based on Placido disk
derived data for the detection of eyes at risk of ectasia. METHODS: One hundred
nineteen eyes of 176 patients were included and separated into two groups, normal
and forme fruste keratoconus (FFKC), using automated corneal classification
software. Normal eyes (n = 114) were classified as negative for keratoconus and
keratoconus suspect and had undergone LASIK with unremarkable follow-up for 4
years. The FFKC group was composed of 62 topographically normal eyes of patients
with keratoconus in the fellow eye. Anterior topographic parameters, obtained
from specular topography using Placido-based indices and corneal wavefront
Zernike coefficients, were compared between groups. Receiver operating
characteristic (ROC) curves were used to identify cut-off points in
discriminating between keratoconic and normal eyes. Validation was performed on
an external group of eyes. RESULTS: A discriminant function was built combining
four corneal wavefront variables and four Placido variables. The area under the
receiver operating characteristic was 0.970 with this eight-variable model. The
validation of this function had 63% sensitivity for detecting FFKC and 100%
sensitivity for detecting keratoconus, with a specificity of 82%. CONCLUSIONS:
Indices generated from corneal wavefront and Placido measurements can assist in
identifying early or mild forms of keratoconus undetected by a Placido-based
neural network program. [J Refract Surg. 2016;32(8):510-516.].
PMID- 27505313
TI - Clinical Evaluation of Reading Performance Using the Salzburg Reading Desk With a
Refractive Rotational Asymmetric Multifocal Intraocular Lens.
AB - PURPOSE: To evaluate functional results and reading performance using the
Salzburg Reading Desk after implantation of a sector-shaped near-embedded,
rotational asymmetrical multifocal intraocular lens (IOL) and a multifocal toric
IOL with a +3.00 diopter (D) near addition. METHODS: In a prospective study, the
LentisMplus and Mplus toric IOLs (Oculentis GmbH, Berlin, Germany) were implanted
in 34 eyes of 18 patients at the University Eye Hospital of Heidelberg.
Uncorrected and corrected distance visual acuity (UDVA, CDVA) and uncorrected and
corrected near visual acuity (UNVA, CNVA) were evaluated using standardized
visual acuity charts (ETDRS). The Salzburg Reading Desk was used to analyze
unilateral and bilateral uncorrected and corrected reading acuity, reading
distance, reading speed, and the smallest log-scaled print size that could be
read effectively at a set (40 cm/80 cm) and subjective chosen near and
intermediate distance. RESULTS: Postoperatively, the median UDVA was 0.08 logMAR
(20/25 Snellen) and the median CDVA was 0.01 logMAR (20/20 Snellen). The median
UNVA was 0.12 logMAR (20/25 Snellen) and the median CNVA was 0.03 logMAR (20/20
Snellen). The median uncorrected reading acuity measured with the Salzburg
Reading Desk for near distance at 40 cm was 0.18 logMAR (20/32 Snellen). The
subjectively preferred near distance was 39 cm and revealed similar visual acuity
results. The best reading acuity for intermediate distance with a median of 0.22
logMAR (20/32 Snellen) was achieved at a median distance of 62 cm. CONCLUSIONS:
Reading performance of the multifocal IOL corresponded for near standardized and
individual distance, whereas reading function was better at the patient's
preferred intermediate distance. [J Refract Surg. 2016;32(8):526-532.].
PMID- 27505312
TI - Long-term Effects of LASIK on Corneal Innervation and Tear Neuropeptides and the
Associations With Dry Eye.
AB - PURPOSE: To investigate the associations between dry eye, corneal nerves, and
tear neuroptides in dry eye after LASIK. METHODS: A single visit cross-sectional
study was performed. Twenty participants who had LASIK more than 12 months prior
and 20 healthy participants were recruited. Ocular comfort, tear functions,
ocular surface sensitivity, basal tear collection, and corneal nerve morphology
assessments were conducted. Tear substance P and calcitonin gene-related peptide
(CGRP) concentrations were determined using ELISAs. Differences in variables
between groups were examined using an independent t test or Mann-Whitney U test,
as appropriate. Associations between variables in the post-LASIK group were
examined using a Spearman's correlation test. A P value of less than .05 was
considered significant. RESULTS: Central corneal nerve morphology parameters were
all altered in the post-LASIK group (P < .05). Higher ocular discomfort (P =
.01), tear CGRP concentration (P = .001), and conjunctival sensitivity (P < .009)
were found in the post-LASIK group. There was a positive association between dry
eye symptoms and superior corneal sensitivity (P = .51, P = .02) and tear
substance P concentration (P = .52, P < .03). CONCLUSIONS: This study provides
evidence of the association between tear neuropeptides, conjunctival sensitivity,
and symptoms in symptomatic patients after LASIK. The differences in nerve
morphology, neuropeptide, and ocular surface sensitivity between symptomatic and
asymptomatic patients after LASIK are required to better understand the mechanism
of dry eye after LASIK. [J Refract Surg. 2016;32(8):518-524.].
PMID- 27505314
TI - Pediatric Keratoconus in a Tertiary Referral Center: Incidence, Presentation,
Risk Factors, and Treatment.
AB - PURPOSE: To report the incidence, clinical presentation, risk factors, and
treatment outcome of pediatric keratoconus in a tertiary referral eye hospital in
Beirut, Lebanon. METHODS: In this retrospective study, the authors evaluated all
patients with keratoconus 14 years or younger newly diagnosed at the Beirut Eye
Specialist Hospital, Beirut, Lebanon, between January 2010 and December 2014. The
incidence of pediatric keratoconus among all pediatric patients and among
patients with keratoconus of all ages was assessed. Patients with pediatric
keratoconus were evaluated for keratoconus stage, initial presentation,
uncorrected distance visual acuity, corrected distance visual acuity (CDVA),
corneal topography, and pachymetry. Patients were classified according to
different treatment regimen groups and different follow-up visits were evaluated.
RESULTS: During 5 years, 16,808 patients were examined, of whom 2,972 were 14
years or younger. A total of 541 patients were diagnosed as having keratoconus;
of those, 16 were 14 years or younger at the time of diagnosis. Hence, the
incidence of keratoconus was 0.53% among pediatric patients and 3.78% among adult
patients (> 14 years). Initial presentation was during routine checkup (1 of 16)
for allergic conjunctivitis (3 of 16), reduced vision (10 of 16), and corneal
hydrops (mimicking keratitis) (2 of 16). Except for 2 patients lost to follow-up,
all eyes received corneal cross-linking treatment and 16 eyes received additional
intracorneal ring segment implantation. CONCLUSIONS: The incidence of pediatric
keratoconus indicates that increased awareness for keratoconus among children is
needed, mainly in cases of family history of keratoconus, ocular
allergy/pruritus, poor CDVA, corneal hydrops, and/or high astigmatism. [J Refract
Surg. 2016;32(8):534-541.].
PMID- 27505315
TI - Comparison of Simulated Keratometric Changes Following Wavefront-Guided and
Wavefront-Optimized Myopic Photorefractive Keratectomy.
AB - PURPOSE: To determine the relationship between change in simulated keratometry
and corrected refractive error in both wavefront-guided and wavefront-optimized
myopic photorefractive keratectomy (PRK), and to determine whether there is a
difference in this relationship between these two ablation profiles. METHODS:
Sixty-eight patients received wavefront-guided PRK in one eye and wavefront
optimized PRK in the contralateral eye. The changes in simulated keratometry and
corresponding refractive changes for both were determined at 1 year
postoperatively. Linear regression was employed to calculate the slope of change
in simulated keratometry (DeltaK) for change in refractive error (DeltaSE) for
both wavefront-guided and wavefront-optimized PRK and compared. The mean ratio
DeltaK/DeltaSE was also calculated for both wavefront-guided and wavefront
optimized PRK and compared. RESULTS: There was no significant difference in the
ratio of DeltaK to DeltaSE between wavefront-optimized and wavefront-guided PRK
by both linear regression modeling and comparison of the mean ratio
DeltaK/DeltaSE. Linear regression modeling revealed that the ratio of
DeltaK/DeltaSE was greater for small amounts of change in refractive error and
smaller for large amounts of change in refractive error. This trend was only
statistically significant for the wavefront-optimized group when comparing the
means of the ratio DeltaK/DeltaSE (P = .0287). CONCLUSIONS: The change in corneal
curvature induced for a given degree of refractive correction was similar for
both wavefront-optimized and wavefront-guided PRK. For both, a proportionally
smaller amount of corneal flattening was required for larger degrees of
refractive correction compared to smaller degrees. [J Refract Surg.
2016;32(8):542-548.].
PMID- 27505316
TI - Influence of Pachymetry and Intraocular Pressure on Dynamic Corneal Response
Parameters in Healthy Patients.
AB - PURPOSE: To evaluate the influence of pachymetry, age, and intraocular pressure
in normal patients and to provide normative values for all dynamic corneal
response parameters (DCRs) provided by dynamic Scheimpflug analysis. METHODS:
Seven hundred five healthy patients were included in this multicenter
retrospective study. The biomechanical response data were analyzed to obtain
normative values with their dependence on corrected and clinically validated
intraocular pressure estimates developed using the finite element method (bIOP),
central corneal thickness (CCT), and age, and to evaluate the influence of bIOP,
CCT, and age. RESULTS: The results showed that all DCRs were correlated with bIOP
except deflection amplitude (DefA) ratio, highest concavity (HC) radius, and
inverse concave radius. The analysis of the relationship of DCRs with CCT
indicated that HC radius, inverse concave radius, deformation amplitude (DA)
ratio, and DefA ratio were correlated with CCT (rho values of 0.343, -0.407,
0.444, and -0.406, respectively). The age group subanalysis revealed that
primarily whole eye movement followed by DA ratio and inverse concave radius were
the parameters that were most influenced by age. Finally, custom software was
created to compare normative values to imported examinations. CONCLUSIONS: HC
radius, inverse concave radius, DA ratio, and DefA ratio were shown to be
suitable parameters to evaluate in vivo corneal biomechanics due to their
independence from IOP and their correlation with pachymetry and age. The creation
of normative values allows the interpretation of an abnormal examination without
the need to match every case with another normal patient matched for CCT and IOP.
[J Refract Surg. 2016;32(8):550-561.].
PMID- 27505318
TI - Reversible Femtosecond Laser-Assisted Endokeratophakia Using Cryopreserved
Allogeneic Corneal Lenticule.
AB - PURPOSE: To evaluate outcomes, reversibility, and wound healing response after
the femtosecond laser-assisted endokeratophakia procedure in a rabbit model.
METHODS: Allogeneic rabbit corneal lenticules were cryopreserved in liquid
nitrogen for 3 months. Twenty rabbits underwent the monocular endokeratophakia
procedure and were divided into four groups according to the follow-up periods.
The first three groups were killed at 3 days, 2 weeks, and 6 months after
endokeratophakia, respectively. The rabbits in the fourth group received re
extraction of implanted lenticules at 6 months after endokeratophakia and were
killed at 1 month after re-extraction. The rabbits were monitored by slit-lamp
microscopy, ultrasonic pachymetry, in vivo confocal microscopy, optical coherence
tomography (OCT), Corvis ST tonometry (Oculus Optikgerate, Wetzlar, Germany), and
Ocular Response Analyzer (Reichert Ophthalmic Instruments, Depew, NY). The tissue
responses were analyzed by immunohistochemistry and transmission electron
microscopy. RESULTS: After endokeratophakia, corneal clarity improved continually
with time. The changes in the refraction and corneal thickness were stable after
implantation and could be reversed after re-extracting the lenticules. The
interfaces were clearly visible on confocal microscopy and transmission electron
microscopy images over the entire follow-up period. There were significant
numbers of TUNEL-positive keratocytes in lenticules after endokeratophakia. CD11b
positive cells and deposition of fibronectin and tenascin were observed at
earlier follow-up times. No alpha-smooth muscle actin-positive fibroblasts could
be detected. In addition, the corneal biomechanics parameters were not
significantly increased after endokeratophakia. CONCLUSIONS: The endokeratophakia
procedure using allogeneic cryopreserved lenticules was clinically stable and
could be reversed. The wound healing response was mild, limited, and produced no
scars. [J Refract Surg. 2016;32(8):569-576.].
PMID- 27505317
TI - Investigating Elastic Anisotropy of the Porcine Cornea as a Function of
Intraocular Pressure With Optical Coherence Elastography.
AB - PURPOSE: To evaluate the elastic anisotropy of porcine corneas at different
intraocular pressures (IOPs) using a noncontact optical coherence elastography
(OCE) technique. METHODS: A focused air-pulse induced low amplitude (<= 10 um)
elastic waves in fresh porcine corneas (n = 7) in situ in the whole eye globe
configuration. A home-built phase-stabilized swept source optical coherence
elastography (PhS-SSOCE) system imaged the elastic wave propagation at different
stepped radial directions. A closed-loop feedback system was used to artificially
control the IOP and the OCE measurements were repeated as the IOP was
incrementally increased from 15 to 30 mm Hg in 5-mm Hg increments. RESULTS: The
OCE measurements demonstrated that the stiffness of the cornea increased as a
function of IOP and elastic anisotropy of the cornea became more pronounced at
higher IOPs. The standard deviation of the modified planar anisotropy coefficient
increased from 0.72 +/- 0.42 at an IOP of 15 mm Hg to 1.58 +/- 0.40 at 30 mm Hg.
CONCLUSIONS: The presented noncontact OCE method was capable of detecting and
assessing the corneal elastic anisotropy as a function of IOP. Due to the
noninvasive nature and small amplitude of the elastic wave, this method may be
able to provide further information about corneal health and integrity in vivo.
[J Refract Surg. 2016;32(8):562-567.].
PMID- 27505319
TI - Circulating miR-148b-3p and miR-409-3p as biomarkers for heart failure in
patients with mitral regurgitation.
AB - BACKGROUND: MicroRNAs (miRs) regulate gene expression in heart failure.
Circulating miRs as biomarkers for heart failure in mitral regurgitation patients
(MR) remain unexplored. METHODS: This case-control study enrolled 32 MR patients
with heart failure, 16 asymptomatic MR patients, and 12 control subjects without
heart failure. We used next generation sequencing to study the gene expression
profiles in the sera, and quantitative RT-PCR to study serum and tissue miRs in
the left atria. RESULTS: Next generation sequencing analysis and enrichment
analysis showed that 25 miRs were differentially expressed in the sera of MR
patients with heart failure compared to control subjects. The circulating miR
148b-3p (p=0.002) and miR-409-3p (p=0.010) were significantly down-regulated in
the MR patients with heart failure compared to control subjects. However, only
circulation miR-148b-3p was significantly down-regulated in the MR patients
without heart failure compared to control subjects (p=0.009). The tissue miR-409
3p was significantly down-regulated in the MR patients with heart failure
compared to 3 purchased normal controls (p=0.041). Notably, the tissue RASGRP3
mRNA, target gene of miR-409-3p, was significantly up-regulated in the MR
patients with heart failure compared to normal controls (p=0.010). The tissue FRY
(p=0.010) and GADD45A (p=0.010) mRNAs, target genes of miR-148b-3p, were
significantly up-regulated in the MR patients with heart failure compared to
normal controls. CONCLUSIONS: Circulating miR-148b-3p might serve as biomarker
for future development of heart failure and miR-409-3p might serve as biomarker
for incident heart failure in MR patients.
PMID- 27505320
TI - The role of implantable cardioverter-defibrillators in patients with continuous
flow left ventricular assist devices - A meta-analysis.
AB - BACKGROUND: Left ventricular assist devices (LVADs) and implantable cardioverter
defibrillators (ICD) are each known to improve mortality in patients with
advanced congestive heart failure (CHF). If ICDs contribute to improved survival
specifically in recipients of LVADs is currently unknown. AIM: To evaluate the
impact of presence of ICD on mortality in continuous flow LVAD recipients.
METHODS: A meta- analysis of available literature was performed. PubMed, Embase
and Google Scholar databases were searched for studies that compared mortality in
continuous flow LVAD patients with ICDs (new implantation or no de-activation)
and without ICDs (including de-activation of existing implant). Pooled analysis
using a fixed effects model was used for outcomes of interest. RESULTS: We
included 3 observational studies for a total of 292 patients (203 (69.5%) with
ICD versus 89 (30.5%) without ICD). The presence of an active ICD was not
associated with improved survival [OR 0.63, 95% CI 0.33-1.18; p=0.15]. In bridge
to transplantation [BT] patients (224 patients, 149 with ICD versus 75 without
ICD), an active ICD was not associated with a higher probability of survivzal [OR
1.47, 95% CI 0.78-2.76; p=0.23]. There was no difference in the occurrence of
severe right ventricular dysfunction or failure between two groups [OR 0.78, 95%
CI 0.42-1.47; p=0.45]. The risk of LVAD related complications were similar [OR
0.68, 95% CI 0.35-1.31; P=0.25]. CONCLUSION: This meta-analysis demonstrates that
there is no survival benefit with ICD in heart failure patients supported with
continuous flow LVAD. There is an urgent need of large-scale randomized trials to
specifically address this issue.
PMID- 27505321
TI - Determinants of temporal changes in galectin-3 level in the general population:
Data of PREVEND.
AB - BACKGROUND: High baseline galectin-3 levels are associated with increased risk
for adverse cardiovascular outcomes in the general population, but determinants
of changes in galectin-3 levels over time have not been established. Therefore,
we aimed to identify determinants of (temporal) change in galectin-3 levels.
METHODS: Galectin-3 plasma levels were measured in a large community based cohort
(PREVEND study) at 3 different time points: at baseline, after ~4 and ~9years.
The association of baseline clinical and biochemical factors and (temporal)
changes in galectin-3 level was assessed using multivariable mixed-effects
regression modeling. RESULTS: In 4355 subjects, galectin-3 plasma levels were
available at all time points (mean age: 48+/-12years; 50% female). Median
galectin-3 level at baseline was 10.7 [8.9-12.7] ng/mL which gradually increased
to 11.5 [9.4-14.3] ng/mL after ~9years. Using mixed-effects regression modeling,
we first validated as independent determinants of baseline circulating galectin
3: eGFR (chi square (chi(2)):210.27, p<0.0001), gender (chi(2):43.85; p<0.0001),
BMI (chi(2):19.68, p=0.0001), NT-proBNP (chi(2):18.76, p=0.0001) and serum
(total) cholesterol (chi(2):8.63, p=0.01). Furthermore, we identified urinary
albumin excretion (chi(2):34.03, p-value: <0.0001) and systolic blood pressure
(chi(2):16.81, p=0.002) as independent determinants of temporal changes of
galectin-3. CONCLUSIONS: In the general population, urinary albumin excretion
>30mg/24h and systolic blood pressure >170mmHg were identified as significant
determinants of dynamic increases in galectin-3 levels over time. These results
implicate that treatment of high blood pressure might be effective to prevent
increasing galectin-3 levels and its associated conditions.
PMID- 27505322
TI - Effect of remote ischemic preconditioning on myocardial injury and inflammatory
response induced by ablation for atrial fibrillation: A randomized controlled
trial.
AB - BACKGROUND: Remote ischemic preconditioning (RIPC) has been suggested to reduce
postoperative release of cardiac and inflammatory markers in patients undergoing
cardiac surgery. This study aimed to evaluate the effect of RIPC on nonischemic
myocardial damage and inflammatory response in patients undergoing radiofrequency
catheter ablation for paroxysmal atrial fibrillation (AF). METHODS: Seventy-two
patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter
ablation were randomized into RIPC or control groups. RIPC (intermittent arm
ischemia through four cycles of 5-min inflation and 5-min deflation of a blood
pressure cuff) was performed once daily on 2 consecutive days before the ablation
and immediately before ablation. Cardiac troponin-I (cTnI), high-sensitive C
reactive protein (hs-CRP), and interleukin (IL)-6 levels were measured before
RIPC/sham RIPC, after the ablation, and 24 and 72h later. The early recurrence of
atrial fibrillation (ERAF) in the two groups was observed over the subsequent
3months. RESULTS: Radiofrequency ablation resulted in a significant rise in cTnI,
hs-CRP, and IL-6 in both groups, which persisted for 72h. The RIPC group showed a
lower increase in cTnI (P<0.001), hs-CRP (P=0.003), and IL-6 (P=0.008) than the
control and tended to have a lower risk of ERAF (hazard ratio [HR]=0.77, 95%
confidence interval [CI]: 0.32-1.88). CONCLUSIONS: These results show that RIPC
before ablation for paroxysmal AF significantly reduces the increase in cTnI, hs
CRP, and IL-6 associated with the procedure and results in a lower risk of ERAF.
These findings suggest that RIPC could provide cardioprotection against
nonischemic myocardial damage.
PMID- 27505323
TI - An unusual case of cardiogenic shock in which thiamine administration led to
reversal of lactic acidosis and heart function recovery: Shoshin beriberi in an
adolescent.
PMID- 27505324
TI - Ulnar pseudoaneurysm after transulnar coronary angiogram treated with
percutaneous ultrasound-guided thrombin injection.
PMID- 27505325
TI - GT-repeat length polymorphism in heme oxygenase-1 promoter determines the effect
of cilostazol on vascular smooth muscle cells.
AB - BACKGROUND: Cilostazol, a potent type 3 phosphodiesterase inhibitor, is found to
reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC)
proliferation. The aim of this study is to investigate whether the inhibitory
effect of cilostazol on VSMC proliferation is operated via heme oxygenase-1 (HO
1). METHODS AND RESULTS: In rat carotid arteries, cilostazol up-regulated HO-1 in
the neointima of balloon-injured arteries. Treatment of human VSMCs with
cilostazol enhanced the expression of HO-1, which was mainly regulated at the
transcriptional level. Small interfering RNA knock-down of HO-1 attenuated the
inhibitory effect of cilostazol on VSMC proliferation, suggesting the critical
role of HO-1 in cilostazol effect. The transcriptional responsiveness of HO-1 to
cilostazol was inversely correlated with the length of GT-repeat in human HO-1
promoter. Deletion and mutational analysis of HO-1 promoter along with chromatin
immunoprecipitation showed that cyclic AMP response element (CRE)-binding protein
(CREB) participated in cilostazol-induced HO-1 transcription. Furthermore,
cilostazol triggered a linkage between the CRE and GT-repeat regions in the HO-1
promoter. The promoting effect of cilostazol on HO-1 expression, proliferation
inhibition, and chromatin conformation in the HO-1 promoter was greater in VSMCs
from subjects with shorter GT-repeat alleles than those with longer alleles.
CONCLUSIONS: Cilostazol inhibits VSMC proliferation involving an association
between CREB and HO-1. The length polymorphism of GT-repeat in human HO-1
promoter determines the effect of cilostazol.
PMID- 27505326
TI - Association between levels of anti-angiogenic isoform of vascular endothelial
growth factor A and pulmonary hypertension.
AB - BACKGROUNDS: Pulmonary hypertension (PH) is characterized by elevated pulmonary
arterial pressure due to vasoconstriction and remodeling of the pulmonary
microvasculature. Vascular endothelial growth factor (VEGF) is a key contributor
for angiogenesis and vasculogenesis. VEGF165b is recently identified as an anti
angiogenic splicing variant of VEGF. The aim of this study was to examine the
association between circulating levels of VEGF165b in PH patients under
consideration with classifications of PH. METHODS AND RESULTS: We measured plasma
levels of VEGF165b in the PH group (pulmonary artery hypertension [PAH], n=26;
chronic thromboembolic pulmonary hypertension [CTEPH], n=13) and control group
(n=30). Circulating levels of VEGF165b were higher in PH group than controls
(97.1 vs. 53.3pg/ml, P<0.01). The multiple regression analysis demonstrated that
the independent factor to determine the plasma levels of VEGF165b was the
presence of PH (P=0.04). Next, we focused on differences in VEGF165b levels and
classifications of PH. Plasma VEGF165b level was higher only in idiopathic PAH
(n=9) than in control (137.1 vs. 53.3pg/ml, P<0.01), but not in PH related to
collagen disease (n=7), congenital heart disease (n=10) and CTEPH (n=13).
CONCLUSIONS: We demonstrated associations between circulating levels of VEGF165b
and classifications of PH. VEGF165b, anti-angiogenic isoform, might contribute to
the pathophysiology in PH, especially in idiopathic PAH. The level of plasma
VEGF165b might be a novel marker that reflects the pathological conditions in
patients with PH.
PMID- 27505327
TI - Subsequent thrombus formation in a patient with apical ballooning.
PMID- 27505328
TI - Role of right ventricular three-dimensional electroanatomic voltage mapping for
arrhythmic risk stratification of patients with corrected tetralogy of Fallot or
other congenital heart disease involving the right ventricular outflow tract.
AB - BACKGROUND: The post-surgical history of repaired congenital heart disease
(rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden
death. Electrical myocardial abnormalities could be a substrate for malignant
ventricular arrhythmias. METHODS AND RESULTS: 146 patients with TOF or other rCHD
involving a subpulmonary right ventricle, considered to be at high arrhythmic
risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM).
Maps showed endocardial scars (<0.5mV) in all cases, mainly involving the RV
outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved.
Total scar extension, expressed as % of total endocardial area, was significantly
higher in patients with QRS >=180ms [4.5% (+/-2.5) vs 2.8% (+/-2.4), p=0.014],
left and right ventricular systolic dysfunction [4.5% (+/-3.2) vs 2.8% (+/-2.3),
p=0.016 and 3.5% (+/-3.0) vs 2.6% (+/-1.9), p=0.03, respectively], premature
ventricular contractions (PVCs) [3.2% (+/-2.6) vs 2.2% (+/-1.8), p<0.05],
exercise-induced PVCs [3.8% (+/-2.4) vs 2.6% (+/-2.2), p=0.01], previous shunt
[4.0% (+/-2.7) vs 2.6% (+/-2.2), p=0.01] and reintervention [4.2% (+/-3.2) vs
2.6% (+/-2.0), p=0.008]. Scar size also showed a positive correlation with
duration of post-surgical follow-up (rho=0.01), age at correction (rho=0.01) and
absolute QRS duration (rho=0.05). CONCLUSIONS: Patients with rCHD involving the
right ventricle show electrical scars with variable distribution, not necessarily
matching with sites of surgical lesions. Scar extension correlates with some of
the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS.
Thus EVM could be considered an additional tool in the assessment of risk
stratification in this particular population.
PMID- 27505329
TI - Geographic and socio-demographic differences in uptake of population-based
screening for atrial fibrillation: The STROKESTOP I study.
AB - BACKGROUND: The rationale behind screening for atrial fibrillation (AF) is to
prevent ischemic stroke. Socio-demographic differences are expected to affect
screening uptake. Geographic differences may provide further insights leading to
targeted interventions for improved uptake. The objective of this study was to
evaluate geographic and socio-demographic differences in uptake of AF screening
in the population-based study STROKESTOP I. METHODS: STROKESTOP was carried out
in two Swedish counties with a total population of 2.3 million inhabitants. Half
of the residents aged 75-76years were randomized to the screening arm: invitation
to clinical examination followed by ambulant ECG recording. Information on each
invited person's residential parish (n=157) was used. On parish-level, aggregated
data for the participants and non-participants, respectively, were obtained with
respect to socioeconomic variables: educational level, disposable income,
immigrant and marital status. Geo-maps displaying participation ratios were
estimated by hierarchical Bayes methods. RESULTS: The overall participation rate
was similar in men and women but lower in Stockholm, 47.6% (5665/11,903) than in
Halland, 61.2% (1495/2443). Participation was clearly associated with the
socioeconomic variables. Participation not taking into account socioeconomy
varied more markedly across the parishes in the Stockholm county (range: 0.65
1.26) than in the Halland county (0.94-1.27). After adjustment for socioeconomic
variables, a geographic variation remained in Stockholm, but not in Halland.
CONCLUSION: Participation in AF screening varied according to socioeconomic
conditions. Geographic variation in participation was marked in the Stockholm
county, with only one screening clinic. Geo-mapping of participation yielded
useful information needed to intervene for improved screening uptake.
PMID- 27505330
TI - A novel polymer-free drug-eluting stent coated with everolimus using nitrogen
doped titanium dioxide film deposition in a porcine coronary restenosis model.
AB - BACKGROUND: Titanium dioxide (TiO2) films have superior biocompatibility and may
be effective as drug-binding matrices for drug-eluting stents (DESs). We sought
to evaluate efficacy of a polymer-free DES coated with everolimus using nitrogen
doped TiO2 film deposition in a porcine coronary restenosis model. METHODS: Forty
coronary arteries in 20 pigs were randomly allocated to group 1 (bare-metal
stents (BMSs), 3.0*18mm, n=10), group 2 (BMSs with nitrogen-doped TiO2 film
deposition, 3.0*18mm, n=10), group 3 [commercial everolimus-eluting stent,
3.0*18mm, n=10], and group 4 (polymer-free everolimus-eluting stent using
nitrogen-doped TiO2 film deposition, 3.0*18mm, n=10). Stents were randomly
implanted in the left anterior descending coronary artery and left circumflex
artery with stent:artery ratio of 1.3. Four weeks later, pigs underwent follow-up
coronary angiography and were sacrificed for histopathologic analysis. RESULTS:
Percent area stenosis was greater in group 1 compared to groups 3 and 4 (46.4+/
13.8% vs. 30.2+/-11.7% vs. 29.2+/-8.9%, respectively, p=0.005). Fibrin score was
lower in groups 1 and 2, compared to groups 3 and 4: 0.87+/-0.67 vs. 0.76+/-0.61
vs. 2.27+/-0.24 vs. 1.75+/-0.31, respectively, p<0.001). Injury score and
inflammation score were not different. Comparison between DES showed a higher
fibrin score in group 3 than group 4 (2.27+/-0.24 vs. 1.75+/-0.31, p=0.023).
CONCLUSIONS: In a porcine model of coronary restenosis, a novel polymer-free DES
using nitrogen-doped TiO2 film deposition shows higher biocompatibility and
compares favorably with a commercial DES.
PMID- 27505331
TI - Evolution of acute ischemic stroke therapy from lysis to thrombectomy: Similar or
different to acute myocardial infarction?
AB - Acute ischemic stroke remains a major global cause of death, permanent
disability, and dementia. For nearly two decades, intravenous tissue plasminogen
activator (tPA) has been the only recommended therapy, albeit administered within
the recommended time window (i.e., <4.5h). However, intravenous tPA is associated
with modest recanalization rates, with a majority of patients having poor
functional outcomes despite timely administration. Endovascular therapy has
recently been introduced as adjunctive management of acute ischemic stroke. First
generation endovascular thrombectomy devices have failed to improve outcomes
compared with intravenous tPA. However, recent randomized trials utilizing stent
retrievers demonstrated that these devices improve functional outcomes in
patients with acute ischemic stroke secondary to large-artery occlusion.
Introduction of stent retrieves has begun a new era for acute ischemic stroke
therapy. This comprehensive review discusses the evolution of acute ischemic
stroke therapy over the last two decades, with emphasis on recent randomized
trials evaluating stent retrievers. Additionally, similarities and differences
between the evolution of therapy in ST elevation myocardial infarction and acute
ischemic stroke will be highlighted.
PMID- 27505332
TI - Neonatal epicardial-derived progenitors aquire myogenic traits in skeletal
muscle, but not cardiac muscle.
AB - BACKGROUND/OBJECTIVES: Epicardium-derived progenitor cells (EPDCs) differentiate
into all heart cell types in the embryonic heart, yet their differentiation into
cardiomyocytes in the adult heart is limited and poorly described. This may be
due to EPDCs lacking myogenic potential or the inert adult heart missing
regenerative signals essential for directed differentiation of EPDCs. Herein, we
aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal
mouse myocardium, as well as in skeletal muscle. The two latter tissues have an
intrinsic capability to develop and regenerate, in contrast to the adult heart.
METHODS: Highly purified mouse EPDCs were transplanted into damaged neonatal and
adult myocardium as well as regenerating skeletal muscle. Co-cultures with
skeletal myoblasts were used to distinguish fusion independent myogenic
conversion. RESULTS: No donor EPDC-derived cardiomyocytes were observed in
hearts. In contrast, a remarkable contribution of EPDCs to skeletal muscle
myofiber formation was evident in vivo. Furthermore, co-cultures of EPDCs with
myoblasts showed that EPDCs became part of multinucleated fibers and appeared to
acquire myogenic traits independent of a fusion event. Fluorescence activated
cell sorting of EPDCs co-cultured with and without myoblasts and subsequent qRT
PCR of 64 transcripts established that the myogenic phenotype conversion was
accomplished through induction of a transcriptional myogenic program. CONCLUSION:
These results suggest that EPDCs may be more myogenic than previously
anticipated. But, the heart may lack factors for induction of myogenesis of
EPDCs, a scenario that should be taken into consideration when aiming for repair
of damaged myocardium by stem cell transplantation.
PMID- 27505333
TI - Sarcopenia and physical activity in older male cardiac patients.
AB - BACKGROUND: There is little information on the association of sarcopenia with
physical activity in elderly cardiac patients. This study determined differences
in physical activity and cutoff values for physical activity according to the
presence or absence of sarcopenia in elderly male cardiac patients. METHODS AND
RESULTS: Sixty-seven consecutive men aged >=65 years with cardiac disease were
enrolled. We defined sarcopenia using the European Working Group on Sarcopenia in
Older People algorithm. Patients were divided into the sarcopenia group (n=25)
and the non-sarcopenia group (n=42). In the patients with and without sarcopenia
of physical activities were evaluated to determine cutoff values of physical
activity. RESULTS: After adjusting for patient characteristics, both the average
daily number of steps (3361.43+/-793.23 vs. 5991.55+/-583.57 steps, P=0.021) and
the average daily energy expenditure of physical activity (71.84+/-22.19 vs.
154.57+/-16.18kcal, P=0.009) were significantly lower in the sarcopenia versus
non-sarcopenia group. Receiver-operating characteristic analysis identified a
cutoff value for steps of physical activity of 3551.80steps/day for 1 week, with
a sensitivity of 0.73 and 1-specificity of 0.44 and a cutoff value for energy
expenditure of physical activity of 85.17kcal/day for 1 week, with a sensitivity
of 0.73 and 1-specificity of 0.27. CONCLUSIONS: Physical activity in the male
cardiac patients with sarcopenia was significantly lower than that in those
without sarcopenia. The cutoff values reported here may be useful values to aid
in the identification of elderly male cardiac patients with sarcopenia.
PMID- 27505334
TI - Association between preoperative depression and long-term survival following
coronary artery bypass surgery - A systematic review and meta-analysis.
AB - BACKGROUND: Depression is common in patients with cardiovascular disease. The
importance of preoperative depression for long-term survival following coronary
artery bypass grafting (CABG) is not well known. The aim was to provide a summary
estimate of the association between preoperative depression and long-term
survival in adults who underwent CABG. METHODS: We did a systematic search of
MEDLINE, EMBASE, Cochrane Library, PsycINFO, Web of Science, and PubMed from
inception to November, 2015, including cohort studies with at least one month of
follow-up that reported hazard ratios (HR) and 95% confidence intervals (CI) for
long-term all-cause mortality following CABG in patients with preoperative
depression compared to non-depressed patients. Two reviewers independently
extracted data on populations, exposure, outcome, risk of bias, and quality of
evidence. We calculated HR and 95% CIs for all-cause mortality using random
effects meta-analyses and performed subgroup and sensitivity analyses. RESULTS:
Seven studies were included with a combined study population of 89,490 patients
(4002 depressed/85,488 non-depressed). All studies observed a positive
association between preoperative depression and all-cause mortality, and in 4
studies the association was statistically significant. Patients with depression
had a pooled hazard ratio of 1.46 (95% CI: 1.23-1.73, p<0.0001) for all-cause
mortality with moderate heterogeneity (I(2)=50.1%, p=0.061). CONCLUSIONS: This
systematic review and meta-analysis indicates that patients with preoperative
depression are at increased risk for long-term, all-cause mortality following
CABG compared with those without depression. Systematic screening for depression
prior to cardiac surgery could identify those at higher risk.
PMID- 27505335
TI - Intensive atorvastatin improves endothelial function and decreases ADP-induced
platelet aggregation in patients with STEMI undergoing primary PCI: A single
center randomized controlled trial.
AB - BACKGROUND: Intensive atorvastatin may be beneficial for patients with ST segment
elevated myocardial infarction (STEMI). However, its effects on endothelial and
residual platelet function remain uninvestigated in these patients. METHODS: This
single-center single-blinded prospective randomized controlled trial included
STEMI patients undergoing PCI, aiming to investigate the acute effects of
intensive atorvastatin (40mg) vs. standard atorvastatin (20mg) on serum
endothelin-1 (ET-1) and ADP-induced platelet clot strength (MA-ADP), which were
measured before and after 7days of atorvastatin treatment respectively. MA-ADP
was measured by thromboelastography. The tolerance and safety of intensive
atorvastatin therapy in these patients were also observed. RESULTS: A total of
120 patients (60 patients in the intensive group and 60 patients in the standard
group) with STEMI, who are undergoing primary PCI, were included into this study
(mean age, 63.5years). Patients from these two groups were matched for baseline
characteristics. Atorvastatin did not significantly affect the serum level of LDL
C or CRP in either the standard or intensive group. Furthermore, ET-1 did not
significantly change following treatment with atorvastatin in the standard group.
However, intensive treatment with atorvastatin significantly reduced ET-1 serum
level (0.65+/-0.38pmol/L vs. 0.49+/-0.21pmol/L, P<0.05) and achieved a greater
reduction of MA-ADP (49.2+/-12.1 vs. 38.4+/-17.4mm, P<0.05). In addition,
although not statistically significant, patients assigned to the intensive group
appeared to suffer from less major adverse cardiovascular events. CONCLUSIONS:
Periprocedural intensive atorvastatin is associated with improved endothelial
function and platelet inhibition, and is well-tolerated in STEMI patients
undergoing PCI.
PMID- 27505336
TI - Anti-inflammatory diet and 10-year (2002-2012) cardiovascular disease incidence:
The ATTICA study.
AB - BACKGROUND/OBJECTIVES: The aim of the present work was to evaluate the
association between the inflammatory potential of the diet and the 10-year
cardiovascular disease (CVD) incidence in the ATTICA Study, and whether this is
modified by the baseline presence or absence of metabolic syndrome (MetS).
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). 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) definition. A
proxy dietary anti-inflammatory index (D-AII) score computed using participants'
diet records. RESULTS: The 10-year fatal or non-fatal CVD event rate was 157
cases/1000 participants. After adjusting for several confounding factors, an anti
inflammatory diet, as expressed by higher DII scores, was borderline associated
with 10-year CVD incidence (OR3rd tertile vs. 1st tertile=0.98, 95%CI: 0.96
1.01). This inverse association was also verified among participants without MetS
at baseline (OR3rd tertile vs. 1st tertile=0.97, 95%CI: 0.94-0.99), but not among
participants with the MetS. CONCLUSIONS: Results of the present work verified the
protective effect of an anti-inflammatory diet towards the 10-year CVD incidence
among participants without MetS. In contrast, the presence of MetS already at
baseline seemed to impede this anti-inflammatory diet protective effect, which
underlines the independent importance of MetS on CVD risk.
PMID- 27505337
TI - Phaeochromocytoma and transient left ventricular apical ballooning syndrome.
PMID- 27505338
TI - Long-term major adverse cardiovascular events and quality of life after coronary
angiography in elderly patients with acute coronary syndrome.
AB - BACKGROUND: Although the elderly comprise the majority of acute coronary syndrome
(ACS) patients, limited data exist on major adverse cardiovascular events (MACEs)
and quality of life (QoL). OBJECTIVES: To study MACEs and QoL prospectively in
ACS patients >70years referred for coronary angiography. METHODS: A prospective
observational study that included ACS patients >70years undergoing coronary
angiography. The outcomes were MACEs and QoL 3years after inclusion. MACEs were
defined as death, recurrent ACS, new-onset of heart failure and repeated
revascularization by coronary artery bypass grafting (CABG) or percutaneous
coronary intervention (PCI). A QoL questionnaire was completed by the patients
along with a physical examination and a personal interview at the 3-year follow
up. Multivariate analysis was performed to identify the predictors for MACEs.
RESULTS: In total, 138 patients (mean age 78.8+/-3.8years) with ACS were included
in the study. Mean follow-up was 1196+/-296days. In all, 42% of the patients had
MACEs and 25% had post-ACS heart failure. The mortality rate was 11%. After
adjusting for significant cardiovascular risk factors, the following factors were
significantly associated with MACEs: Age, high-sensitive troponin T (hsTNT), use
of diuretics and reduced left ventricular ejection fraction (LVEF). Furthermore,
the QoL evaluated with SF-36 in survivors from ACS at the end of study was
similar to the QoL in an age-matched healthy Swedish population. CONCLUSIONS: In
this prospective study on elderly ACS patients MACEs still occurred in 42% of the
cases (despite low mortality and good QoL), with post-ACS heart failure as the
most important event.
PMID- 27505339
TI - Efficacy and safety of biodegradable polymer sirolimus-eluting stents versus
durable polymer drug-eluting stents: A meta-analysis of randomized trials.
AB - BACKGROUND: A meta-analysis was performed to investigate the safety and efficacy
of biodegradable polymer sirolimus-eluting stents (BP-SESs) compared with durable
polymer drug-eluting stents (DP-DESs). METHODS: Online databases, including
PubMed, EMBASE and the Cochrane Library, were searched for randomized controlled
trials that compared BP-SESs and DP-DESs and reported rates of overall and
cardiac mortality, myocardial infarction (MI), stent thrombosis (ST), target
lesion revascularization (TLR), target vessel revascularization (TVR) and late
lumen loss (LLL). RESULTS: A total of 15 studies investigating 14,187 patients
were included in the meta-analysis. The BP-SESs significantly reduced the risk of
late ST (OR: 0.57; 95% CI: 0.33-0.98; p=0.04), very late ST (OR: 0.53; 95% CI:
0.29-0.97; p=0.04) and in-stent LLL (MD: -0.06, 95% CI: -0.11 to -0.01; p=0.01)
compared with the DP-DESs but did not improve mortality (OR: 0.95; 95% CI: 0.81
1.11; p=0.52), cardiac mortality (OR: 0.89; 95% CI: 0.72-1.10; p=0.27), MI (OR:
0.90; 95% CI: 0.76-1.08; p=0.27), TLR (OR: 0.95; 95% CI: 0.81-1.11; p=0.51), TVR
(OR: 0.96; 95% CI: 0.81-1.13; p=0.62) or in-segment LLL (MD: -0.03, 95% CI: -0.06
0.01; p=0.10). CONCLUSIONS: In this meta-analysis of randomized controlled
trials, the BP-SESs were superior to the DP-DESs in terms of late ST, very late
ST and in-stent LLL. Further large randomized controlled trials with long-term
follow-up are required to validate the benefits of BP-SESs.
PMID- 27505340
TI - Optical coherence tomography for hypertensive pulmonary vasculature.
AB - BACKGROUND: Optical coherence tomography (OCT) is an intravascular imaging
modality capable of providing in situ images of tissues at near histologic
resolution. In this study we examine the utility of OCT in identifying vascular
changes related to pulmonary arterial hypertension (PAH) and chronic
thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: OCT of four
different distal pulmonary arteries was performed during right heart
catheterization in 87 patients, 64 patients with PAH and 23 patients with CTEPH.
The mean luminal diameter measured by OCT for all patients was 2.26mm. Intimal
thickening was significantly increased in all PAH patients (0.26+/-0.05mm in
idiopathic PAH, 0.24+/-0.03mm in connective tissue disease related PAH, 0.26+/
0.06mm in congenital heart disease related PAH and 0.22+/-0.04mm in CTEPH,
respectively) compared with controls (0.13+/-0.03mm) (all p<0.05). An intimal
thickness of >=0.176mm had a 91% positive predictive value for pulmonary
hypertension. The anatomic abnormalities revealed by OCT tended to be severe in
the idiopathic PAH group and mild in the CTEPH group. Signs of intravascular webs
were found in 60.9% of CTEPH patients, but no other patients. Intimal thickness
was moderately correlated with pulmonary arterial pressure and pulmonary vascular
resistance (r=0.423 and 0.439, respectively, p<0.001). CONCLUSIONS: OCT provides
important information for assessment of pulmonary arterial remodeling in patients
with PAH and improves diagnostic capability of angiographically undetected distal
thrombotic lesions in patients with CTEPH.
PMID- 27505341
TI - Electrophysiocardiogram: For the first time EPCG has been recorded on human body
surface.
AB - Since ECG was invented in 1903, this is the first time in history that a full
information multi-band and multi-linear electrophysiological cardiogram has been
used to successfully scan and record on the human body surface. Since it is able
to record various multi-band, multi-track linear electric signals of cardiac
electrophysiological activities that correspond to different regions of the
entire heart, it has thus been denominated as "electrophysiocardiogram" (EPCG). A
traditional ECG is always represented by a characteristic wave form, which
resembles a string. For a long period of time, ECG has had a lot of mysteries
surrounding it, it maybe because ECG has a lot of mixed signals buried in such
convolutionary forms, which limits the amount of the signals that are discernable
and determinable. For the first time, the EPCG technology has allowed cardiac
signals to be convoluted into the linear wave form, which is then processed
through various new approaches featuring multiple frequency bands, multiple
dimensions and multiple patterns, and consequentially recorded as the following
types of signals within the ranges of P wave and T wave: multiple frequency band
signals, signals of different regions and different locations, forward waves and
negative waves. Therefore, EPCG may help to solve many puzzling scientific
questions regarding heart, such as exactly how many electric signals are involved
in heart excitation, pacing, conduction and action, as well as many other
intriguing questions about heart, and thus would become a very helpful tool in
clinical practice.
PMID- 27505342
TI - Atrial fibrillation classification and association between the natural frequency
and the autonomic nervous system.
AB - BACKGROUND: The feasibility study of the natural frequency (omega) obtained from
a second-order dynamic system applied to an ECG signal was discovered recently.
The heart rate for different ECG signals generates different omega values. The
heart rate variability (HRV) and autonomic nervous system (ANS) have an
association to represent cardiovascular variations for each individual. This
study further analyzed the omega for different ECG signals with HRV for atrial
fibrillation classification. METHODS: This study used the MIT-BIH Normal Sinus
Rhythm (nsrdb) and MIT-BIH Atrial Fibrillation (afdb) databases for healthy human
(NSR) and atrial fibrillation patient (N and AF) ECG signals, respectively. The
extraction of features was based on the dynamic system concept to determine the
omega of the ECG signals. There were 35,031 samples used for classification.
RESULTS: There were significant differences between the N & NSR, N & AF, and NSR
& AF groups as determined by the statistical t-test (p<0.0001). There was a
linear separation at 0.4s(-1) for omega of both databases upon using the
thresholding method. The feature omega for afdb and nsrdb falls within the high
frequency (HF) and above the HF band, respectively. The feature classification
between the nsrdb and afdb ECG signals was 96.53% accurate. CONCLUSIONS: This
study found that features of the omega of atrial fibrillation patients and
healthy humans were associated with the frequency analysis of the ANS during
parasympathetic activity. The feature omega is significant for different
databases, and the classification between afdb and nsrdb was determined.
PMID- 27505343
TI - A joint allergist/cardiologist classification for thienopyridines
hypersensitivity reactions based on their symptomatic patterns and its impact on
the management strategies.
AB - The role and importance of thienopyridines such as ticlopidine, clopidogrel, and
prasugrel is well-established for several indications, ranging from prevention of
acute coronary syndromes to percutaneous coronary interventions, where the dual
antiplatelet therapy represents the gold standard to avoid denovo coronary
stenosis. However, there is a significant cohort of patients with coronary artery
disease who may manifest hypersensitivity reactions to thienopyridines. The
examination of the various case reports from medical literature leads to identify
mainly four clinical patterns of hypersensitivity to thienopyridines which
involves more frequently cutaneous, hematologic, and articular tissues, therefore
the kind and predominance of clinical symptoms may determine a different clinical
approach to overcome or neutralize thienopyridines hypersensitivity.
PMID- 27505344
TI - Vitamin D deficiency is independently associated with greater prevalence of
erectile dysfunction: The National Health and Nutrition Examination Survey
(NHANES) 2001-2004.
AB - BACKGROUND AND AIMS: Erectile dysfunction (ED) and atherosclerotic cardiovascular
disease (ASCVD) share many common risk factors, and vascular ED is a marker for
increased ASCVD risk. Low 25-hydroxyvitamin D [25(OH)D] concentrations have been
associated with increased ASCVD risk, but less is known regarding the
relationship of low 25(OH)D with ED. We determined whether 25(OH)D deficiency is
associated with ED independent of ASCVD risk factors. METHODS: We performed cross
sectional analyses of 3390 men aged >=20 years free of ASCVD who participated in
NHANES 2001-2004. Serum 25(OH)D was measured by the DiaSorin radioimmunoassay;
deficiency was defined as levels <20 ng/ml (<50 nmol/L). Self-reported ED,
assessed by a single validated question, was defined as men who reported being
"never" or "sometimes able" to maintain an erection. We assessed the relationship
between 25(OH)D deficiency and ED prevalence using adjusted Poisson regression
methods. RESULTS: After accounting for NHANES sampling, the weighted prevalence
of 25(OH)D deficiency and of ED were 30% and 15.2%, respectively. 25(OH)D levels
were lower in men with vs. those without ED (mean 22.8 vs 24.3 ng/mL,
respectively; p = 0.0005). After adjusting for lifestyle variables,
comorbidities, and medication use, men with 25(OH)D deficiency had a higher
prevalence of ED compared to those with levels >=30 ng/ml (Prevalence Ratio 1.30,
95% CI 1.08-1.57). CONCLUSION: In this cross-sectional analysis of a
representative sample of U.S. men, vitamin D deficiency was associated with an
increased prevalence of ED independent of ASCVD risk factors. Additional research
is needed to evaluate whether treating vitamin D deficiency improves erectile
function.
PMID- 27505345
TI - Genomics of variation in nitrogen fixation activity in a population of the
thermophilic cyanobacterium Mastigocladus laminosus.
AB - Variation in phenotypic traits that contribute to fitness influences a
population's evolutionary response and its impact on ecosystem function following
environmental change, yet its amount and nature are rarely known. Here, we
investigated variation in nitrogen (N) fixation activity and its genetic basis
for a random sample of laboratory strains of the cyanobacterium Mastigocladus
laminosus from a N-limited, geothermally influenced stream in Yellowstone
National Park. In a linear mixed-effects model, temperature and genetic
differences among strains were the most important factors explaining variation in
activity. Genome-wide analyses of genetic divergence between groups of strains
that varied in N fixation activity revealed that few loci were strongly
associated with these phenotypic differences. Notably, a single nonsynonymous
polymorphism in the sulfate assimilation gene apsK explained >25% of the
variation in activity at high temperature. We further identified a role for
allelic variation of multiple terminal cytochrome oxidases for different aspects
of N fixation. In addition, genomes of strains that fixed the most N overall
contained a nonsense mutation in a histidine kinase gene that is expected to
disrupt normal protein function and may result in transcriptional rewiring. This
study illustrates how taking complementary approaches to link phenotype and
genotype can inform our understanding of microbial population diversity.
PMID- 27505346
TI - Distinct gene expression profile of Xanthomonas retroflexus engaged in
synergistic multispecies biofilm formation.
AB - It is well known that bacteria often exist in naturally formed multispecies
biofilms. Within these biofilms, interspecies interactions seem to have an
important role in ecological processes. Little is known about the effects of
interspecies interactions on gene expression in these multispecies biofilms. This
study presents a comparative gene expression analysis of the Xanthomonas
retroflexus transcriptome when grown in a single-species biofilm and in dual- and
four-species consortia with Stenotrophomonas rhizophila, Microbacterium oxydans
and Paenibacillus amylolyticus. The results revealed complex interdependent
interaction patterns in the multispecies biofilms. Many of the regulated
functions are related to interactions with the external environment and suggest a
high phenotypic plasticity in response to coexistence with other species.
Furthermore, the changed expression of genes involved in aromatic and branched
chain amino acid biosynthesis suggests nutrient cross feeding as a contributing
factor for the observed synergistic biofilm production when these four species
coexists in a biofilm.
PMID- 27505347
TI - The methanogenic redox cofactor F420 is widely synthesized by aerobic soil
bacteria.
AB - F420 is a low-potential redox cofactor that mediates the transformations of a
wide range of complex organic compounds. Considered one of the rarest cofactors
in biology, F420 is best known for its role in methanogenesis and has only been
chemically identified in two phyla to date, the Euryarchaeota and Actinobacteria.
In this work, we show that this cofactor is more widely distributed than
previously reported. We detected the genes encoding all five known F420
biosynthesis enzymes (cofC, cofD, cofE, cofG and cofH) in at least 653 bacterial
and 173 archaeal species, including members of the dominant soil phyla
Proteobacteria, Chloroflexi and Firmicutes. Metagenome datamining validated that
these genes were disproportionately abundant in aerated soils compared with other
ecosystems. We confirmed through high-performance liquid chromatography analysis
that aerobically grown stationary-phase cultures of three bacterial species,
Paracoccus denitrificans, Oligotropha carboxidovorans and Thermomicrobium roseum,
synthesized F420, with oligoglutamate sidechains of different lengths. To
understand the evolution of F420 biosynthesis, we also analyzed the distribution,
phylogeny and genetic organization of the cof genes. Our data suggest that
although the Fo precursor to F420 originated in methanogens, F420 itself was
first synthesized in an ancestral actinobacterium. F420 biosynthesis genes were
then disseminated horizontally to archaea and other bacteria. Together, our
findings suggest that the cofactor is more significant in aerobic bacterial
metabolism and soil ecosystem composition than previously thought. The cofactor
may confer several competitive advantages for aerobic soil bacteria by mediating
their central metabolic processes and broadening the range of organic compounds
they can synthesize, detoxify and mineralize.
PMID- 27505348
TI - Metagenomic recovery of phage genomes of uncultured freshwater actinobacteria.
AB - Low-GC Actinobacteria are among the most abundant and widespread microbes in
freshwaters and have largely resisted all cultivation efforts. Consequently,
their phages have remained totally unknown. In this work, we have used deep
metagenomic sequencing to assemble eight complete genomes of the first tailed
phages that infect freshwater Actinobacteria. Their genomes encode the
actinobacterial-specific transcription factor whiB, frequently found in
mycobacteriophages and also in phages infecting marine pelagic Actinobacteria.
Its presence suggests a common and widespread strategy of modulation of host
transcriptional machinery upon infection via this transcriptional switch. We
present evidence that some whiB-carrying phages infect the acI lineage of
Actinobacteria. At least one of them encodes the ADP-ribosylating component of
the widespread bacterial AB toxins family (for example, clostridial toxin). We
posit that the presence of this toxin reflects a 'trojan horse' strategy,
providing protection at the population level to the abundant host microbes
against eukaryotic predators.
PMID- 27505349
TI - Illness management and recovery in community practice.
AB - OBJECTIVE: To examine provider competence in providing Illness Management and
Recovery (IMR), an evidence-based self-management program for people with severe
mental illness, and the association between implementation supports and IMR
competence. METHOD: IMR session recordings, provided by 43 providers/provider
pairs, were analyzed for IMR competence using the IMR Treatment Integrity Scale.
Providers also reported on receipt of commonly available implementation supports
(e.g., training, consultation). RESULTS: Average IMR competence scores were in
the "needs improvement" range. Clinicians demonstrated low competence in several
IMR elements: significant other involvement, weekly action planning, action plan
follow-up, cognitive-behavioral techniques, and behavioral tailoring for
medication management. These elements were commonly absent from IMR sessions.
Competence in motivational enhancement strategies and cognitive-behavioral
techniques differed based on the module topic covered in a session. Generally,
receipt of implementation supports was not associated with increased competence;
however, motivational interviewing training was associated with increased
competence in action planning and review. CONCLUSIONS AND IMPLICATIONS FOR
PRACTICE: IMR, as implemented in the community, may lack adequate competence and
commonly available implementation supports do not appear to be adequate.
Additional implementation supports that target clinician growth areas are needed.
(PsycINFO Database Record
PMID- 27505350
TI - Activation of Platinum(IV) Prodrugs by Cytochrome c and Characterization of the
Protein Binding Sites.
AB - Platinum(IV) complexes generally require reduction to reactive Pt(II) species to
exert their chemotherapeutic activity. The process of reductive activation of
(15)N-labeled (OC-6-43)-bis(acetato)diamminedichloridoplatinum(IV), in the
presence of nicotinamide adenine dinucleotide (NADH) and horse heart cytochrome c
(cyt c), was monitored by (1)H,(15)N-HSQC NMR spectroscopy and protein digestion
experiments. It has been shown that cyt c plays a catalytic role in the transfer
of two reducing equivalents from NADH to Pt(IV) species. Noncovalent interactions
between reduced monoaqua cisplatin (cis-[PtCl((15)NH3)2(H2O)](+)) and the
protein, in the proximity of the heme cofactor, and also covalent binding of
platinum to the protein region around Met65 and Met80 take place.
PMID- 27505352
TI - Engineered Nanoparticles as Potential Food Contaminants and Their Toxicity to
Caco-2 Cells.
AB - Engineered nanoparticles (ENPs), such as metallic or metallic oxide nanoparticles
(NPs), have gained much attention in recent years. Increasing use of ENPs in
various areas may lead to the release of ENPs into the environment and cause the
contamination of agricultural and food products by ENPs. In this study, we
selected two important ENPs (zinc oxide [ZnO] and silver [Ag] NPs) as potential
food contaminants and investigated their toxicity via an in vitro model using
Caco-2 cells. The physical properties of ENPs and their effects on Caco-2 cells
were characterized by electron microscopy and energy dispersive X-ray
spectroscopic (EDS) techniques. Results demonstrate that a significant inhibition
of cell viability was observed after a 24-h of exposure of Caco-2 cells to 3-, 6
, and 12-mM ZnO NPs or 0.5-, 1.5-, and 3-mM Ag NPs. The noticeable changes of
cells include the alteration in cell shape, abnormal nuclear structure, membrane
blebbing, and cytoplasmic deterioration. The toxicity of ZnO NPs, but not that of
Ag NPs after exposure to simulated gastric fluid, significantly decreased.
Scanning transmission electron microscopy shows that ZnO and Ag NPs penetrated
the membrane of Caco-2 cells. EDS results also confirm the presence of NPs in the
cytoplasm of the cells. This study demonstrates that ZnO and Ag NPs have
cytotoxic effects and can inhibit the growth of Caco-2 cells.
PMID- 27505353
TI - The Hippo/MST Pathway Member SAV1 Plays a Suppressive Role in Development of the
Prehierarchical Follicles in Hen Ovary.
AB - The Hippo/MST signaling pathway is a critical player in controlling cell
proliferation, self-renewal, differentiation, and apoptosis of most tissues and
organs in diverse species. Previous studies have shown that Salvador homolog 1
(SAV1), a scaffolding protein which functions in the signaling system is
expressed in mammalian ovaries and play a vital role in governing the follicle
development. But the exact biological effects of chicken SAV1 in prehierarchical
follicle development remain poorly understood. In the present study, we
demonstrated that the SAV1 protein is predominantly expressed in the oocytes and
undifferentiated granulosa cells in the various sized prehierarchical follicles
of hen ovary, and the endogenous expression level of SAV1 mRNA appears down
regulated from the primordial follicles to the largest preovulatory follicles (F2
F1) by immunohistochemistry and real-time RT-PCR, respectively. Moreover, we
found the intracellular SAV1 physically interacts with each of the pathway
members, including STK4/MST1, STK3/MST2, LATS1 and MOB2 using western blotting.
And SAV1 significantly promotes the phosphorylation of LATS1 induced by the
kinase of STK4 or STK3 in vitro. Furthermore, SAV1 knockdown by small interfering
RNA (siRNA) significantly increased proliferation of granulosa cells from the
prehierarchical follicles (6-8 mm in diameter) by BrdU-incorporation assay, in
which the expression levels of GDF9, StAR and FSHR mRNA was notably enhanced.
Meanwhile, these findings were consolidated by the data of SAV1 overexpression.
Taken together, the present results revealed that SAV1 can inhibit proliferation
of the granulosa cells whereby the expression levels of GDF9, StAR and FSHR mRNA
were negatively regulated. Accordingly, SAV1, as a member of the hippo/MST
signaling pathway plays a suppressive role in ovarian follicle development by
promoting phosphorylation and activity of the downstream LATS1, may consequently
lead to prevention of the follicle selection during ovary development.
PMID- 27505354
TI - The Hydrated Electron at the Surface of Neat Liquid Water Appears To Be
Indistinguishable from the Bulk Species.
AB - Experiments have suggested that the aqueous electron, e(-)(aq), may play a
significant role in the radiation chemistry of DNA. A recent measurement of the
energy (below vacuum level) of the putative "interfacial" hydrated electron at
the water/vacuum interface, performed using liquid microjet photoelectron
spectroscopy, has been interpreted to suggest that aqueous electrons at the
water/biomolecule interface may possess the appropriate energetics to induce DNA
strand breaks, whereas e(-)(aq) in bulk water lies too far below the vacuum level
to induce such reactions. Other such experiments, however, find no evidence of a
long-lived feature at low binding energy. We employ a variety of computational
strategies to demonstrate that the energetics of the hydrated electron at the
surface of neat liquid water are not significantly different from those of e(
)(aq) in bulk water and as such are incompatible with dissociative electron
attachment reactions in DNA. We furthermore suggest that no stable interfacial
species may exist at all, consistent with the interpretation of certain surface
sensitive spectroscopy measurements, and that even if a short-lived, metastable
species does exist at the vacuum/water interface, it would be extremely difficult
to distinguish, experimentally, from e(-)(aq) in bulk water, using either optical
absorption or photoelectron spectroscopy.
PMID- 27505355
TI - Transitioning to Country Ownership of HIV Programs in Rwanda.
AB - Agnes Binagwaho and colleagues describe how Rwanda achieved country ownership of
its HIV programs.
PMID- 27505357
TI - Inversion method based on stochastic optimization for particle sizing.
AB - A stochastic inverse method is presented based on a hybrid evolutionary
optimization algorithm (HEOA) to retrieve a monomodal particle-size distribution
(PSD) from the angular distribution of scattered light. By solving an
optimization problem, the HEOA (with the Fraunhofer approximation) retrieves the
PSD from an intensity pattern generated by Mie theory. The analyzed light
scattering pattern can be attributed to unimodal normal, gamma, or lognormal
distribution of spherical particles covering the interval of modal size
parameters 46<=alpha<=150. The HEOA ensures convergence to the near-optimal
solution during the optimization of a real-valued objective function by combining
the advantages of a multimember evolution strategy and locally weighted linear
regression. The numerical results show that our HEOA can be satisfactorily
applied to solve the inverse light-scattering problem.
PMID- 27505356
TI - Simultaneous cytosolic delivery of a chemotherapeutic and siRNA using
nanoparticle-stabilized nanocapsules.
AB - We report on nanoparticle-stabilized capsules (NPSCs) as a platform for the co
delivery of survivin-targeted siRNA and tamoxifen. These capsules feature an
inner oil core that provides a carrier for tamoxifen, and is coated on the
surface with positively charged nanoparticles self-assembled with siRNA. The
multifaceted chemical nature of the NPSC system enables the simultaneous delivery
of both payloads directly into the cytosol in vitro. The NPSC co-delivery of
tamoxifen and survivin-targeted siRNA into breast cancer cells disables the
pathways that inhibit apoptosis, resulting in enhanced breast cell death.
PMID- 27505358
TI - Rapid fabrication of a silicon modification layer on silicon carbide substrate.
AB - We develop a kind of magnetorheological (MR) polishing fluid for the fabrication
of a silicon modification layer on a silicon carbide substrate based on chemical
theory and actual polishing requirements. The effect of abrasive concentration in
MR polishing fluid on material removal rate and removal function shape is
investigated. We conclude that material removal rate will increase and tends to
peak value as the abrasive concentration increases to 0.3 vol. %, and the removal
function profile will become steep, which is a disadvantage to surface frequency
error removal at the same time. The removal function stability is also studied
and the results show that the prepared MR polishing fluid can satisfy actual
fabrication requirements. An aspheric reflective mirror of silicon carbide
modified by silicon is well polished by combining magnetorheological finishing
(MRF) using two types of MR polishing fluid and computer controlled optical
surfacing (CCOS) processes. The surface accuracy root mean square (RMS) is
improved from 0.087lambda(lambda=632.8 nm) initially to 0.020lambda(lambda=632.8
nm) in 5.5 h total and the tool marks resulting from MRF are negligible. The PSD
analysis results also shows that the final surface is uniformly polished.
PMID- 27505359
TI - Variability of particle size distribution with respect to inherent optical
properties in Poyang Lake, China.
AB - Suspended particulate matter plays a significant role in the studies of sediment
fluxes, phytoplankton dynamics, and water optical properties. This study focuses
on the relationships between particle size distribution (PSD), water's inherent
optical properties (IOPs), and water constituents. We investigated the complex
waters of Poyang Lake, the largest freshwater lake in China, in wet and dry
seasons during 2008-2011. Because of the distinct temporal-spatial variation of
Poyang Lake, these parameters and relationships also demonstrate seasonal and
regional variability. The variation range of the concentration of suspended
particulate matter is 0.32-69.08 mg/l, with a mean value of 22.21 mg/l. The
median particle size in the dry season is much larger than that of the wet
season. The Junge distribution fits the PSD of Poyang Lake very well in the scope
of 6.21-331 MUm. Furthermore, the slopes of the PSD range from 3.54 to 4.69, with
a mean value of 4.11, with the steepest slopes (>4.5) occurring in the waters
around Songmen Mountain Island and the northern waterway. A negative correlation
was found between median particle size (Dv50) and the mass-specific
absorption coefficient at 443 nm [apm(443)] for both wet and dry seasons.
Identical to analogous waters, the spectral slopes of the PSD correlate well with
the spectral slopes of the attenuation coefficient, but with different fitted
formulas. In the dry season, the particle size can better explain the variability
of the scattering coefficient, while the mass-specific scattering coefficient is
better explained by the apparent density. However, no similar results were found
for the wet season. In addition, the spectral slopes of the backscattering
coefficient correlated well with the PSD slope, and the bulk refractive index
calculated from the backscattering ratio and PSD slope can indicate the particle
composition of Poyang Lake. Overall, the knowledge on the PSD and IOPs gained in
this study broadens our understanding of water optics in highly turbid water
columns.
PMID- 27505360
TI - Photonic generation of high frequency millimeter-wave and transmission over
optical fiber.
AB - A novel technique of photonic generation of millimeter-waves beyond the presently
reported 120 GHz and with a wider tunability (~240 GHz) is proposed and
demonstrated through a simulation experiment. The scheme consists of generating
24 times the frequency of a conventional low frequency microwave source using a
combination of a LiNbO3 Mach-Zehnder modulator and four-wave mixing in
a semiconductor optical amplifier. The filtering of a high frequency sideband and
the suppression of a carrier are achieved by incorporating an optical band pass
and fiber Bragg grating filters, respectively. Next, the spectral purity of the
generated millimeter-wave parameters is evaluated after propagation through a
conventional fiber of different lengths by digitally modulating it at 2.5 Gbps
and generating an eye diagram. The constraints on the selection of the frequency
of the millimeter-wave and length of fiber are discussed. The present method of
millimeter-wave generation and distribution will find applications in photonic
up/down conversion, phase-array antennas, photonic sensors, radars, and terahertz
applications.
PMID- 27505361
TI - Experimental demonstration of highway I2V using visible light communications.
AB - A visible light communication (VLC)-based intelligent transportation system (ITS)
has drawn much interest from telematics and automobile industries due to its
enhanced safety and cost effectiveness. Within the framework of ITS, vehicle-to
vehicle and infrastructure-to-vehicle (I2V) communications have largely been
considered. I2V can be viewed as an important ITS technology that broadcasts
traffic information from fixed traffic infrastructure. In this paper, an
experimental demonstration of a highway VLC-based I2V system is presented. For
robust and reliable detection in the VLC-based I2V, the receiver structure of the
proposed system is comprised of an optical filter, a color filter, and a Fresnel
lens. We consider two primary atmospheric conditions in the highway I2V, i.e.,
sunlight and cloud effects. To alleviate these adverse effects, we propose an
efficient and robust zone detection (ZD) and adaptive decision threshold (ADT)
method. The sunlight effect is reduced predominantly by the ZD, while the cloud
effect is lessened significantly by the ADT. The experimental results demonstrate
that the proposed method performs well to counter the sunlight and cloud effects.
It is found that the proposed ZD and ADT method provides an approximate SNR
improvement ranging from 16 to 26 dB, depending upon measurement times of the
day.
PMID- 27505362
TI - Extending lock-in methods: term isolation detection of nonlinear signals.
AB - We show that components of a nonlinear signal can be measured using phase
sensitive detection at unconventional demodulation frequencies, allowing us to
isolate individual terms from the signal. To demonstrate this technique,
autocorrelation measurements of an ultrafast pulsed laser were performed using
two-photon absorption. In this example, the isolation of individual
autocorrelation terms may provide internal consistency checks to improve the
precision and accuracy of pulse characterization. More generally, this scheme can
be extended to a range of nonlinear measurements. As a demonstration, we analyze
a three-photon autocorrelation model, showing that many nonlinear signals can be
studied with this method. We anticipate that term isolation detection will find
application in a broad range of experiments, such as multidimensional Fourier
transform spectroscopy or coherent anti-Stokes Raman spectroscopy.
PMID- 27505363
TI - Diffraction by random Ronchi gratings.
AB - In this work, we obtain analytical expressions for the near-and far-field
diffraction of random Ronchi diffraction gratings where the slits of the grating
are randomly displaced around their periodical positions. We theoretically show
that the effect of randomness in the position of the slits of the grating
produces a decrease of the contrast and even disappearance of the self-images for
high randomness level at the near field. On the other hand, it cancels high-order
harmonics in far field, resulting in only a few central diffraction orders.
Numerical simulations by means of the Rayleigh-Sommerfeld diffraction formula are
performed in order to corroborate the analytical results. These results are of
interest for industrial and technological applications where manufacture errors
need to be considered.
PMID- 27505364
TI - Effect of direction of incident light on the basic performance of a
TeO2 acousto-optic tunable filter.
AB - The selection of the ultrasonic polar angle is vitally important to the
performance of an acousto-optic tunable filter (AOTF). The effects of ultrasonic
angle on various properties of AOTFs were studied. Then, according to the
selected ultrasonic angle, the changes of internal and external separation angles
were analyzed in detail when the light was incident upon the crystal surface in
two different ways. Additionally, the drift of diffracted light caused by
chromatic aberration was analyzed, and an appropriate compensation wedge angle
was calculated by the improved derivation formula. The external separation angle
increased obviously after placing a wedge angle on the output end. Finally, the
effect of incident beam with a cone angle on spectral bandwidth and diffraction
efficiency is discussed.
PMID- 27505365
TI - Simultaneous displacement and slope measurement in electronic speckle pattern
interferometry using adjustable aperture multiplexing.
AB - This paper suggests the use of adjustable aperture multiplexing (AAM), a method
which is able to introduce multiple tunable carrier frequencies into a three-beam
electronic speckle pattern interferometer to measure the out-of-plane
displacement and its first-order derivative simultaneously. In the optical
arrangement, two single apertures are located in the object and reference light
paths, respectively. In cooperation with two adjustable mirrors, virtual images
of the single apertures construct three pairs of virtual double apertures with
variable aperture opening sizes and aperture distances. By setting the aperture
parameter properly, three tunable spatial carrier frequencies are produced within
the speckle pattern and completely separate the information of three
interferograms in the frequency domain. By applying the inverse Fourier transform
to a selected spectrum, its corresponding phase difference distribution can thus
be evaluated. Therefore, we can obtain the phase map due to the deformation as
well as its slope of the test surface from two speckle patterns which are
recorded at different loading events. By this means, simultaneous and dynamic
measurements are realized. AAM has greatly simplified the measurement system,
which contributes to improving the system stability and increasing the system
flexibility and adaptability to various measurement requirements. This paper
presents the AAM working principle, the phase retrieval using spatial carrier
frequency, and preliminary experimental results.
PMID- 27505366
TI - Quantitative vibration analysis using a single fringe pattern in time-average
speckle interferometry.
AB - In this paper, a novel technique for quantitative vibration analysis using time
average electronic speckle pattern interferometry is proposed. An amplitude
varied time-average refreshing reference frame method is used to capture a fringe
pattern with a better fringe contrast than the conventional reference frame
technique. The recorded fringe patterns with improved contrast provide better
mode shape visibility and are easier to process. A derivative-based regularized
phase tracker model is used to retrieve vibration amplitudes from a single fringe
pattern. The method does not require a phase shifter to obtain the mode shape or
amplitude. The method provides unwrapped amplitude and amplitude derivatives maps
directly, so a separate phase unwrapping process is not required. Experimental
work is carried out using a circular aluminum plate test specimen and the results
are compared with a finite element method modal analysis. Both experimental and
numerical results show that the proposed method is robust and accurate.
PMID- 27505367
TI - Zernike polynomials as a basis for modal fitting in lateral shearing
interferometry: a discrete domain matrix transformation method.
AB - A Zernike-polynomials-based wavefront reconstruction method for lateral shearing
interferometry is proposed. Shear matrices are calculated using matrix
transformation instead of mathematical derivation. Simulation results show that
the shear matrices calculated using the proposed method are the same as those
obtained from mathematical derivation. The advantage of the proposed method is
that high order shear matrices can be obtained easily; thus, wavefront
reconstruction can be extended to higher order Zernike terms, and reconstruction
accuracy can be improved.
PMID- 27505368
TI - Colossal Kerr nonlinearity based on electromagnetically induced transparency in a
five-level double-ladder atomic system.
AB - The paper is aimed at modeling the enhanced Kerr nonlinearity in a five-level
double-ladder-type atomic system based on electromagnetically induced
transparency (EIT) by using the semi-classical density matrix method. We present
an analytical model to explain the origin of Kerr nonlinearity enhancement. The
scheme also results in a several orders of magnitude increase in the Kerr
nonlinearity in comparison with the well-known four- and three-level atomic
systems. In addition to the steady-state case, the time-dependent Kerr
nonlinearity and the switching feature of EIT-based colossal Kerr nonlinearity is
investigated for the proposed system.
PMID- 27505369
TI - RCWA-EIS method for interlayer grating coupling.
AB - The grating coupling efficiencies for interlayer connection (overlaid chips) were
previously calculated using the new rigorous coupled-wave analysis equivalent
index-slab (RCWA-EIS) method. The chip-to-chip coupling efficiencies were
determined for rectangular-groove (binary) gratings. In the present work, the
search algorithms used in the RCWA-EIS method are optimized giving rise to
improved definition of equivalent indices. Further, the versatility of the RCWA
EIS method is demonstrated by extending it to (nonbinary) parallelogramic
gratings, sawtooth gratings, and volume gratings. The finite-difference time
domain method is used to verify the results. This demonstrates the flexibility of
the RCWA-EIS method in analyzing arbitrary 1D gratings.
PMID- 27505370
TI - Analysis of junction temperature and modification of luminous flux degradation
for white LEDs in a thermal accelerated reliability test.
AB - An accelerated aging test is the main method in evaluation of the reliability of
light-emitting diodes (LEDs), and the first goal of this study is to investigate
how the junction temperature (Tj) of the LED varies during accelerated aging. The
Tj measured by the forward voltage method shows an upward trend over the aging
time, which gives a variation about 6 degrees C-8 degrees C after 3,000 h of
aging under an ambient temperature of 80 degrees C. The second goal is to
investigate how the variation of Tj affects the lifetime estimation. It is
verified that at a certain aging stage, as Tj increases, the normalized luminous
flux linearly decreases with variation rate of microns (MU) (1/ degrees C). Then,
we propose a method to modify the luminous flux degradation with the Tj and MU to
meet the requirements of a constant degradation rate in the data fitting. The
experimental results show that with the proposed method, the accelerated
lifetimes of samples are bigger than that of the current method with increment
values from 8.8% to 21.4% in this research.
PMID- 27505371
TI - Hybrid algorithm for three-dimensional flame chemiluminescence tomography based
on imaging overexposure compensation.
AB - Flame tomography of chemiluminescence is a necessary combustion diagnostic
technique that provides instantaneous 3D information on flame structure and
excited species concentrations. During combustion diagnostics, imaging
overexposure always causes missing information, which obviously decreases the
accuracy in further reconstructions. In order to compensate imaging overexposure,
a hybrid algorithm combining weight correction and Tikhonov's regularization is
proposed in this paper. The intensity of the overexposure region can be estimated
via the accumulation of weight coefficients. Meanwhile, Tikhonov's regularization
is utilized to ameliorate the quality of reconstruction. The numerical simulation
quantitatively evaluates the performance of the hybrid algorithm. Additionally,
an experiment system consisting of 12 cameras was established to reconstruct the
3D combustion structure of axisymmetric flame with different exposure time
settings. This work further investigates dynamic nonaxisymmetric propane
diffusion flame. The obtained results show that the hybrid algorithm can
effectively reveal the flame structure less influenced by imaging overexposure
and achieve better results.
PMID- 27505372
TI - Field of view of limitations in see-through HMD using geometric waveguides.
AB - Geometric waveguides are being integrated into head-mounted display (HMD)
systems, where having see-through capability in a compact, lightweight form
factor is required. We developed methods for determining the field of view (FOV)
of such waveguide HMD systems and have analytically derived the FOV for
waveguides using planar and curved geometries. By using real ray-tracing methods,
we are able to show how the geometry and index of refraction of the waveguide, as
well as the properties of the coupling optics, impact the FOV. Use of this
analysis allows one to determine the maximum theoretical FOV of a planar or
curved waveguide-based system.
PMID- 27505373
TI - Dependence of depth of focus on spherical aberration of optical systems.
AB - This paper presents a theoretical analysis and computation of aberration
coefficients of the third and fifth order of transverse spherical aberration of
an optical system, which generates a ray bundle with a diameter of a geometric
optical circle of confusion smaller than a predetermined limit value. Equations
were derived for the calculation of aberration coefficients of an optical system,
which satisfy given conditions, and for the determination of the maximum possible
depth of focus for given conditions.
PMID- 27505374
TI - Analysis of three-dimensional interference patterns of an inclined capillary.
AB - We study the interference patterns from an inclined capillary tube filled with
liquid by using the ray tracing method and interference theory. A beautiful
elliptical pattern is found on the screen, with refined fringes embedded in it.
Particularly, the fringes on top of the pattern are continuously swallowed to the
center with the angle of incidence increasing. In addition, a method is
demonstrated to determine the refractive index of the liquid and the wavelength
of the incident light by measuring the capillary tilt of every 10-fringe being
swallowed, which looks like fringe crossover, with respect to the change of the
inclined angle of the capillary.
PMID- 27505375
TI - Intensity and angle-of-arrival spectra of laser light propagating through axially
homogeneous buoyancy-driven turbulence.
AB - Frequency spectra obtained from the measurements of light intensity and angle of
arrival (AOA) of parallel laser light propagating through the axially
homogeneous, axisymmetric buoyancy-driven turbulent flow at high Rayleigh numbers
in a long (length-to-diameter ratio of about 10) vertical tube are reported. The
flow is driven by an unstable density difference created across the tube ends
using brine and fresh water. The highest Rayleigh number is about
8*109. The aim of the present work is to find whether the conventional
Obukhov-Corrsin scaling or Bolgiano-Obukhov (BO) scaling is obtained for the
intensity and AOA spectra in the case of light propagation in a buoyancy-driven
turbulent medium. Theoretical relations for the frequency spectra of log
amplitude and AOA fluctuations developed for homogeneous isotropic turbulent
media are modified for the buoyancy-driven flow in the present case to obtain the
asymptotic scalings for the high and low frequency ranges. For low frequencies,
the spectra of intensity and vertical AOA fluctuations obtained from measurements
follow BO scaling, while scaling for the spectra of horizontal AOA fluctuations
shows a small departure from BO scaling.
PMID- 27505376
TI - Adaptive multidirectional frequency domain filter for noise removal in wrapped
phase patterns.
AB - In order to avoid the detrimental effects of excessive noise in the phase fringe
patterns of a laser digital interferometer over the accuracy of phase unwrapping
and the successful detection of mechanical fatigue defects, an effective method
of adaptive multidirectional frequency domain filtering is introduced based on
the characteristics of the energy spectrum of localized wrapped phase patterns.
Not only can this method automatically set the cutoff frequency, but it can also
effectively filter out noise while preserving the image edge information.
Compared with the sine and cosine transform filtering and the multidirectional
frequency domain filtering, the experimental results demonstrate that the image
filtered by our method has the fewest number of residues and is the closest to
the noise-free image, compared to the two aforementioned methods, demonstrating
the effectiveness of this adaptive multidirectional frequency domain filter.
PMID- 27505377
TI - High-resolution and wide-bandwidth light intensity fiber optic displacement
sensor for MEMS metrology.
AB - We report on the design, properties, and applications of a high-resolution and
wide-bandwidth light intensity fiber optic displacement sensor for
microelectromechanical system (MEMS) metrology. There are two types of structures
that the system is dedicated to: vibrating with both high and low frequencies. In
order to ensure high-frequency and high-resolution measurements, frequency down
mixing and selective signal processing were applied. The obtained effective
measuring bandwidth ranges from single hertz to 1 megahertz. The achieved
resolution presented here is 116 pm/Hz1/2 and 138
pm/Hz1/2 for low-frequency and high-frequency operation modes,
respectively, whereas the measurement of static displacement is 100 MUm.
PMID- 27505378
TI - Automated alignment of a reconfigurable optical system using focal-plane sensing
and Kalman filtering.
AB - Automation of alignment tasks can provide improved efficiency and greatly
increase the flexibility of an optical system. Current optical systems with
automated alignment capabilities are typically designed to include a dedicated
wavefront sensor. Here, we demonstrate a self-aligning method for a
reconfigurable system using only focal plane images. We define a two lens optical
system with 8 degrees of freedom. Images are simulated given misalignment
parameters using ZEMAX software. We perform a principal component analysis on the
simulated data set to obtain Karhunen-Loeve modes, which form the basis set whose
weights are the system measurements. A model function, which maps the state to
the measurement, is learned using nonlinear least-squares fitting and serves as
the measurement function for the nonlinear estimator (extended and unscented
Kalman filters) used to calculate control inputs to align the system. We present
and discuss simulated and experimental results of the full system in operation.
PMID- 27505379
TI - Design of apochromatic lens with large field and high definition for machine
vision.
AB - Precise machine vision detection for a large object at a finite working distance
(WD) requires that the lens has a high resolution for a large field of view
(FOV). In this case, the effect of a secondary spectrum on image quality is not
negligible. According to the detection requirements, a high resolution
apochromatic objective is designed and analyzed. The initial optical structure
(IOS) is combined with three segments. Next, the secondary spectrum of the IOS is
corrected by replacing glasses using the dispersion vector analysis method based
on the Buchdahl dispersion equation. Other aberrations are optimized by the
commercial optical design software ZEMAX by properly choosing the optimization
function operands. The optimized optical structure (OOS) has an f-number (F/#) of
3.08, a FOV of phi60 mm, a WD of 240 mm, and a modulated transfer function (MTF)
of all fields of more than 0.1 at 320 cycles/mm. The design requirements for a
nonfluorite material apochromatic objective lens with a large field and high
definition for machine vision detection have been achieved.
PMID- 27505380
TI - Nonparaxial geometrical Ronchi test for spherical mirrors: an inverse ray-tracing
approach.
AB - A geometrical model based on an inverse ray-tracing approach to describe the
Ronchi test for a concave spherical mirror is presented. In contrast to the
conventional ray-tracing method, which refers to information unavailable in
ronchigrams, the proposed model provides an explicit relation between the
available information in the ronchigram and the parameters of the setup (radius
of the sphere, position of the source, position and orientation of the
observation, and grating planes). This allows for extracting the parameters of
interest by a simple fitting procedure, as demonstrated by an application. The
derived model exhibits new unexplored potential applications of the Ronchi test,
establishing it as a very useful, simple, and universal tool for optical
evaluation.
PMID- 27505381
TI - Surface-enhanced coherent anti-Stokes Raman imaging of lipids.
AB - This work describes in detail a wide-field surface-enhanced coherent anti-Stokes
Raman scattering (CARS) microscope, which enables enhanced detection of sample
structures in close proximity (~100 nm) of the substrate interface. Unlike
conventional CARS microscopy, where the sample is illuminated with freely
propagating light, the current implementation uses evanescent fields to drive
Raman coherences across the entire object plane. By coupling the pump and Stokes
excitation beams to the surface plasmon-polariton mode at the interface of a 30
nm thick gold film, we obtained strong CARS signals from cholesteryl oleate
droplets adhered to the surface. The surface-enhanced CARS imaging system
visualizes lipid structures with vibrational selectivity using illumination doses
per unit area that are more than four orders of magnitude lower than in point
scanning CARS microscopy.
PMID- 27505382
TI - Degradation nonuniformity in the solar diffuser bidirectional reflectance
distribution function.
AB - The assumption of angular dependence stability of the solar diffuser (SD)
throughout degradation is critical to the on-orbit calibration of the reflective
solar bands (RSBs) in many satellite sensors. Recent evidence has pointed to the
contrary, and in this work, we present a thorough investigative effort into the
angular dependence of the SD degradation for the Visible Infrared Imaging
Radiometer Suite (VIIRS) onboard the Suomi National Polar-orbiting Partnership
(SNPP) satellite and for the twin Moderate-resolution Imaging Spectroradiometer
(MODIS) onboard Terra and Aqua spacecrafts. One common key step in the RSB
calibration is the use of the SD degradation performance measured by an
accompanying solar diffuser stability monitor (SDSM) as a valid substitute for
the SD degradation factor in the direction of the RSB view. If SD degradations
between these two respective directions do not maintain the same relative
relationship over time, then the unmitigated use of the SDSM-measured SD
degradation factor in the RSB calibration calculation will generate bias, and
consequently, long-term drift in derived science products. We exploit the
available history of the on-orbit calibration events to examine the response of
the SDSM and the RSB detectors to the incident illumination reflecting off SD
versus solar declination angle and show that the angular dependency, particularly
at short wavelengths, evolves with respect to time. The generalized and the
decisive conclusion is that the bidirectional reflectance distribution function
(BRDF) of the SD degrades nonuniformly with respect to both incident and outgoing
directions. Thus, the SDSM-based measurements provide SD degradation factors that
are biased relative to the RSB view direction with respect to the SD. The
analysis also reveals additional interesting phenomena, for example, the sharp
behavioral change in the evolving angular dependence observed in Terra MODIS and
SNPP VIIRS. For SNPP VIIRS the mitigation for this "SD degradation nonuniformity
effect" with respect to angles relies on a "hybrid methodology" using lunar-based
calibration to set the reliable long-term baseline. For MODIS, the use of earth
targets in the major release Collection 6 to improve calibration coefficients and
time-dependent response-versus-scan-angle characterization inherently averts the
use of SD and its associated issues. The work further supports that having an
open-close operational capability for the space view door can minimize SD
degradation and its associated effects due to solar exposure, and thus provide
long-term benefits for maintaining calibration and science data accuracy.
PMID- 27505383
TI - Compensation of fringe distortion for phase-shifting three-dimensional shape
measurement by inverse map estimation.
AB - For three-dimensional shape measurement, phase-shifting techniques are widely
used to recover the objective phase containing height information from images of
projected fringes. Although such techniques can provide an accurate result in
theory, there might be considerable error in practice. One main cause of such an
error is distortion of fringes due to nonlinear responses of a measurement
system. In this paper, a postprocessing method for compensating distortion is
proposed. Compared to other compensation methods, the proposed method is flexible
in two senses: (1) no specific model of nonlinearity (such as the gamma model) is
needed, and (2) no special calibration data are needed (only the observed image
of the fringe is required). Experiments using simulated and real data confirmed
that the proposed method can compensate multiple types of nonlinearity without
being concerned about the model.
PMID- 27505384
TI - Characterization of optical polarization properties for liquid crystal-based
retarders.
AB - We present the analysis and implementation of a set of experimental procedures to
characterize optical polarization properties as a function of the applied voltage
for liquid-crystal variable retarders (LCVRs) in the transmission mode. The
studied properties are those involved in the operation of the LCVRs and,
generally, are the most significant for optical applications: retardance,
diattenuation, optical axes position, and output depolarization effects. The
correct characterization of these polarization properties can be useful to
improve results or estimate errors in applications using these devices. The
results obtained show good accuracy and good agreement with the expected results.
PMID- 27505385
TI - Smart electro-optical iris diaphragm based on liquid crystal film coating with
photoconductive polymer of poly(N-vinylcarbazole).
AB - This study develops a light shutter whose transmittance can be tuned electro
optically. The liquid crystal (LC) film applies the photoconductive material of
poly(N-vinylcarbazole) (PVK) based on twisted nematic (TN) liquid crystals (LCs).
The hole-transport layer of PVK could reduce the built-in electric field of the
LC film under the exposure of UV light. The driving voltage is considerably
decreased with the aid of UV light exposure. The repeating optical switching is
performed under sunlight illumination with an external bias of electric field ~5
V. Further, it could be operated under a parallel/cross-polarizer to change the
light beam/ring as an iris and used to automatically block the UV light to
protect an optical integrated system.
PMID- 27505386
TI - Ground-based detection of nighttime clouds above Manila Observatory (14.64
degrees N, 121.07 degrees E) using a digital camera.
AB - Ground-based cloud detection at nighttime is achieved by using cameras, lidars,
and ceilometers. Despite these numerous instruments gathering cloud data, there
is still an acknowledged scarcity of information on quantified local cloud cover,
especially at nighttime. In this study, a digital camera is used to continuously
collect images near the sky zenith at nighttime in an urban environment. An
algorithm is developed to analyze pixel values of images of nighttime clouds. A
minimum threshold pixel value of 17 is assigned to determine cloud occurrence.
The algorithm uses temporal averaging to estimate the cloud fraction based on the
results within the limited field of view. The analysis of the data from the
months of January, February, and March 2015 shows that cloud occurrence is low
during the months with relatively lower minimum temperature (January and
February), while cloud occurrence during the warmer month (March) increases.
PMID- 27505387
TI - Volume holographic printing using unconventional angular multiplexing for three
dimensional display.
AB - We propose and demonstrate a volume holographic printing method for dynamic three
dimensional (3D) display with an expanded space-bandwidth product (SBP) using
unconventional angular multiplexing techniques. By wavefront encoding of the 3D
scene, with the help of computer-generated holography, the object beam is loaded
onto a 2D phase spatial light modulator (SLM) with a limited SBP. The printing
method then writes a single hologram through the interference of the object beam
with a reference beam as a holographic element (hogel) in the volume holographic
polymer. In addition, multiple 3D scenes can be recorded and dynamically
reconstructed by angular multiplexing in the same hogel location. The SBP can be
increased by two orders of magnitude compared to the conventional holographic
printing method, showing the potential to realize a dynamic and high-resolution
3D display.
PMID- 27505388
TI - Least-squares method for data reconstruction from gradient data in deflectometry.
AB - Least-squares integration (LSI) and radial basis function integration (RBFI)
methods are widely used to reconstruct specular surface shapes from gradient data
in a deflectometry measurement. The traditional LSI method requires gradient data
having a rectangular grid, and the RBFI method is effective at handling small
size measurement data sets. Practically, the amount of gradient data is rather
large, and data grids are in quadrilateral shapes. With this in mind, a new LSI
method is proposed to integrate gradient data, which is based on an approximation
that the normal vector of one point is perpendicular to the vectors connecting
points at either side. A small measurement data set integrated by the RBFI method
is employed as a supplementary constraint of the proposed method. Simulation and
experimental results show that this proposed method is effective and accurate at
handling deflectometry measurement.
PMID- 27505389
TI - Improved quantitative visualization of hypervelocity flow through wavefront
estimation based on shadow casting of sinusoidal gratings.
AB - A simple noninterferometric optical probe is developed to estimate wavefront
distortion suffered by a plane wave in its passage through density variations in
a hypersonic flow obstructed by a test model in a typical shock tunnel. The probe
has a plane light wave trans-illuminating the flow and casting a shadow of a
continuous-tone sinusoidal grating. Through a geometrical optics, eikonal
approximation to the distorted wavefront, a bilinear approximation to it is
related to the location-dependent shift (distortion) suffered by the grating,
which can be read out space-continuously from the projected grating image. The
processing of the grating shadow is done through an efficient Fourier fringe
analysis scheme, either with a windowed or global Fourier transform (WFT and FT).
For comparison, wavefront slopes are also estimated from shadows of random-dot
patterns, processed through cross correlation. The measured slopes are suitably
unwrapped by using a discrete cosine transform (DCT)-based phase unwrapping
procedure, and also through iterative procedures. The unwrapped phase information
is used in an iterative scheme, for a full quantitative recovery of density
distribution in the shock around the model, through refraction tomographic
inversion. Hypersonic flow field parameters around a missile-shaped body at a
free-stream Mach number of ~8 measured using this technique are compared with the
numerically estimated values. It is shown that, while processing a wavefront with
small space-bandwidth product (SBP) the FT inversion gave accurate results with
computational efficiency; computation-intensive WFT was needed for similar
results when dealing with larger SBP wavefronts.
PMID- 27505390
TI - Single-shot dual-wavelength phase reconstruction in off-axis digital holography
with polarization-multiplexing transmission.
AB - A new system for single-shot dual-wavelength digital holographic microscopy with
polarization-multiplexing path-shared transmission is presented. The key feature
of the optical configuration is that the interference waves of two wavelengths
having orthogonal polarization can transmit in the same interferometer paths at
the same time, and two polarizers orthogonal to each other are placed in front of
the CCD to realize single-shot recording of two holograms. The correlative
filtering algorithm of the spatial-frequency spectrum for dual-wavelength digital
holograms is reliable and efficient in the dual-wavelength path-shared
configuration. The phase reconstruction in dual-wavelength digital holographic
imaging is achieved by using this filtering algorithm. The experiment results of
phase reconstruction of a groove grating demonstrate the reliability and validity
of this optical configuration and the correlative filtering algorithm. This
polarization-multiplexing configuration for dual-wavelength digital holography is
compact and has more flexibility for the replacement of different-wavelength
lasers.
PMID- 27505391
TI - Effects of femtosecond laser pulse width on the formation of microstructured
silicon.
AB - We experimentally investigated the properties of surface microstructured silicon
fabricated by 15 and 130 fs laser pulses. By changing parameters of femtosecond
laser pulses, including laser flux, actual pulse acting time, and laser peak
intensity, we found that the average height of spikes on the surface of
microstructured silicon are only determined by the laser peak intensity. These
results are important for the preparation and structure control of
microstructured silicon.
PMID- 27505392
TI - Diffraction-based sensitivity analysis for an external occulter laboratory
demonstration.
AB - An external flower-shaped occulter flying in formation with a space telescope can
theoretically provide sufficient starlight suppression to enable direct imaging
of an Earth-like planet. Occulter shapes are scaled to enable experimental
validation of their performance at laboratory dimensions. Previous experimental
results have shown promising performance but have not realized the full
theoretical potential of occulter designs. Here, we develop a two-dimensional
diffraction model for optical propagations for occulters incorporating
experimental errors. We perform a sensitivity analysis, and comparison with
experimental results from a scaled-occulter testbed validates the optical model
to the 10-10 contrast level. The manufacturing accuracy along the edge
of the occulter shape is identified as the limiting factor to achieving the
theoretical potential of the occulter design. This hypothesis is experimentally
validated using a second occulter mask manufactured with increased edge feature
accuracy and resulting in a measured contrast level approaching the 10
12 level-a better than one order of magnitude improvement in performance.
PMID- 27505393
TI - Creating Airy beams employing a transmissive spatial light modulator.
AB - We present a detailed study of two novel methods for shaping the light optical
wavefront by employing a transmissive spatial light modulator (SLM).
Conventionally, optical Airy beams are created by employing SLMs in the so-called
all-phase mode. In the first method, a numerically simulated lens phase
distribution is loaded directly onto the SLM, together with the cubic phase
distribution. An Airy beam is generated at the focal plane of the numerical lens.
We provide for the first time, to the best of our knowledge, quantitative
properties of the formed Airy beam. We derive the formula for deflection of the
intensity maximum of the so-formed Airy beam, which is different from the
quadratic deflection typical of Airy beams. We cross-validate the derived formula
by both simulations and experiment. The second method is based on the fact that a
system consisting of a transmissive SLM sandwiched between two polarizers can
create a transmission function with negative values. This observation alone has
the potential for various other wavefront modulations where the transmission
function requires negative values. As an example for this method, we demonstrate
that a wavefront can be modulated by passing the SLM system with transmission
function with negative values by loading an Airy function distribution directly
onto the SLM. Since the Airy function is a real-valued function but also with
negative values, an Airy beam can be generated by direct transfer of the Airy
function distribution onto such an SLM system. In this way, an Airy beam is
generated immediately behind the SLM. As both new methods do not employ a
physical lens, the two setups are more compact than conventional setups for
creating Airy beams. We compare the performance of the two novel methods and the
properties of the created Airy beams.
PMID- 27505394
TI - Development of an optical microscopy system for automated bubble cloud analysis.
AB - Recently, the number of uses of bubbles has begun to increase dramatically, with
medicine, biofuel production, and wastewater treatment just some of the
industries taking advantage of bubble properties, such as high mass transfer. As
a result, more and more focus is being placed on the understanding and control of
bubble formation processes and there are currently numerous techniques utilized
to facilitate this understanding. Acoustic bubble sizing (ABS) and laser
scattering techniques are able to provide information regarding bubble size and
size distribution with minimal data processing, a major advantage over current
optical-based direct imaging approaches. This paper demonstrates how direct
bubble-imaging methods can be improved upon to yield high levels of automation
and thus data comparable to ABS and laser scattering. We also discuss the added
benefits of the direct imaging approaches and how it is possible to obtain
considerable additional information above and beyond that which ABS and laser
scattering can supply. This work could easily be exploited by both industrial
scale operations and small-scale laboratory studies, as this straightforward and
cost-effective approach is highly transferrable and intuitive to use.
PMID- 27505395
TI - Annealing effects on microstructure and laser-induced damage threshold of
HfO2/SiO2 multilayer mirrors.
AB - HfO2/SiO2 periodic multilayer high reflection mirrors have
been prepared by a reactive electron-beam evaporation technique. The deposited
mirrors were annealed in the temperature range from 300 degrees C to 500 degrees
C. The effects of annealing on optical, microstructural, and laser-induced damage
characteristics of the mirrors have been investigated. The high reflection band
of the mirror shifts toward a shorter wavelength with increasing annealing
temperature. As-deposited and annealed mirrors show polycrystalline structure
with a monoclinic phase of HfO2. Crystalinity and grain size increase
upon annealing. The laser-induced damage threshold (LIDT) has been assessed using
a 532 nm pulsed laser at a pulse width of 7 ns. The LIDT value of the multilayer
mirror increases from 44.1 J/cm2 to 77.6 J/cm2 with
annealing up to 400 degrees C. The improvement of LIDT with annealing is
explained through oxygen vacancy defects as well as grain-size-dependent thermal
conductivity. Finally, the observed laser damage morphology, such as circular
scalds and ablated multilayer stacks with terrace structure, are analyzed.
PMID- 27505396
TI - Linearity enhancement of scale factor in an optical interrogated micromechanical
accelerometer.
AB - A method to reduce the residual stress of support arms in an optical interrogated
micromechanical accelerometer is proposed in order to enhance the linearity of
the scale factor of the accelerometer. First, the behavior of residual stress in
support arms is analyzed in detail, and the simulation of shape curvature caused
by residual stress in aluminum-made support arms is completed using finite
element analysis. Then, by comparing two different materials of support arms
(aluminum-made and silicon-made support arms), a modified fabrication is
introduced in order to reduce the unexpected residual stress in support arms.
Finally, based on contrast experiments, the linearity of the scale factor of
accelerometers with aluminum-made and silicon-made support arms is measured using
the force feedback test system, respectively. Results show that the linearity of
the scale factor of the accelerometer with silicon-made support arms is 0.85%,
which is reduced about an order of magnitude compared to that of the
accelerometer with aluminum-made support arms with the linearity of scale factor
of 7.48%; linearity enhancement of the scale factor is validated. This allows
accuracy improvement of the optical interrogated micromechanical accelerometer in
the application of inertial navigation and positioning.
PMID- 27505397
TI - All-fiber, narrow linewidth and linearly polarized fiber laser in a single-mode
multimode-single-mode cavity.
AB - We report the design of an all-fiber, linearly polarized Yb-doped fiber laser at
1064 nm with a narrow linewidth and high output power required by the master
oscillator of the amplifier for high-power spectral beam combining. The laser has
achieved linearly polarized output with a polarization extinction ratio of 23 dB,
a narrow linewidth of <=52 pm, and an output power of 32.7 W. Such performance
was obtained by the cavity design that incorporated a wavelength-shifted PM fiber
Bragg grating pair and single-mode-multimode-single-mode structure.
PMID- 27505398
TI - High Raman-to-fluorescence ratio of Rhodamine 6G excited with 532 nm laser
wavelength using a closely packed, self-assembled monolayer of silver
nanoparticles.
AB - A highly efficient Raman-to-fluorescence ratio of Rhodamine 6G is obtained by
means of 532 nm laser wavelength, which is in close proximity of the dye's
absorption maximum. Closely packed, gap-filled self-assembled monolayers of
silver nanoparticles were produced to observe the Raman signals of Rhodamine 6G.
Two mechanisms contribute to detect the Raman signals of the fluorescent sample:
surface-enhanced Raman scattering (SERS) and nanomaterial surface energy transfer
(NSET). Self-assembled monolayers of silver nanoparticles with different coverage
densities and also those filled with probe molecules were prepared through
variations of the substrate's immersion time in a nanoparticle solution and
drying the substrate, respectively. Examination of the effects of these two
factors on the plasmonic response and SERS efficiency of the substrate revealed
that in a gap-filled dense coverage, near-field interactions dominate, which
remarkably increase the Raman-to-fluorescence ratio (RFR). To have a perfect
dense coverage, the efficient immersion time was obtained at about 48 h. Drying
the substrates also caused further enhancement in RFR through filling
interparticle spaces with dye molecules and, accordingly, an increase in NSET
efficiency.
PMID- 27505399
TI - Scintillation analysis of multiple-input single-output underwater optical links.
AB - Multiple-input single-output (MISO) techniques are employed in underwater
wireless optical communication (UWOC) links to mitigate the degrading effects of
oceanic turbulence. In this paper, we consider a MISO UWOC system which consists
of a laser beam array as transmitter and a point detector as receiver. Our aim is
to find the scintillation index at the detector in order to quantify the system
performance. For this purpose, the average intensity and the average of the
square of the intensity are derived in underwater turbulence by using the
extended Huygens-Fresnel principle. The scintillation index and the average bit
error-rate (?BER?) formulas presented in this paper depend on the oceanic
turbulence parameters, such as the rate of dissipation of the mean-squared
temperature, rate of dissipation of kinetic energy per unit mass of fluid,
Kolmogorov microscale, and the ratio of temperature to salinity contributions to
the refractive index spectrum, the link length, and the wavelength. Recently, we
have derived an equivalent structure constant of atmospheric turbulence and
expressed it in terms of the oceanic turbulence parameters [Appl. Opt.55, 1228
(2016)APOPAI0003-693510.1364/AO.55.001228]. In the formulation in this paper,
this equivalent structure constant is utilized, which enables us to employ the
existing similar formulation valid in atmospheric turbulence.
PMID- 27505400
TI - Real-time two-dimensional beam steering with gate-tunable materials: a
theoretical investigation.
AB - A leaky-wave antenna is proposed that furnishes two-dimensional (2-D) beam
scanning in both elevation and azimuth planes via electrical control in real
time, and at a single frequency. The structure consists of a graphene sheet on a
metal-backed substrate. The 2-D beam-scanning performance is achieved through the
proper biasing configuration of graphene. Traditional pixel-by-pixel electrical
control makes the biasing network a huge challenge for chip-scale designs in the
terahertz regime and beyond. The method presented here enables dynamic control by
applying two groups of one-dimensional biasing on the sides of the sheet. They
are orthogonal and decoupled, with one group offering monotonic impedance
variation along one direction, and the other sinusoidal impedance modulation
along the other direction. The conductivity profile of the graphene sheet for a
certain radiation angle, realized by applying proper voltage to each pad
underneath the sheet, is determined by a holographic technique and can be
reconfigured electronically and desirably. Such innovative biasing design makes
real-time control of the beam direction and beamwidth simple and highly
integrated. The concept is not limited to graphene-based structures, and can be
generalized to any available gate-tunable material system.
PMID- 27505401
TI - PEG Insertion in Patients With Dementia Does Not Improve Nutritional Status and
Has Worse Outcomes as Compared With PEG Insertion for Other Indications.
AB - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are commonly utilized
as a method of enteral feeding in patients unable to obtain adequate oral
nutrition. Although some studies have shown improved mortality in select
populations, the safety and effectiveness of PEG insertion in patients with
dementia compared with those with other neurological diseases or head and neck
malignancy remains less well defined. OBJECTIVE: To evaluate the nutritional
effectiveness, rate of rehospitalization, and risk of mortality among patients
with dementia compared with patients with other neurological diseases or head and
neck cancers who undergo PEG placement. MATERIALS AND METHODS: We conducted a
retrospective analysis from a prospective database of patients who underwent PEG
placement at an academic tertiary center between 2008 and 2013. The following
data were collected: indication for PEG, patient demographics, biochemical
markers of nutritional status rehospitalization, and survival rates. RESULTS:
During the study period, 392 patients underwent PEG tube placement. Indications
for PEG were dementia (N=165, group A), cerebrovascular accident (N=124, group
B), and other indications such as oropharyngeal cancers and motor neuron disease
(N=103, group C). The mean follow-up time after PEG was 18 months (range, 3 to 36
mo). No differences in baseline demographics were noted. PEG insertion in the
dementia (group A) neither reduced the rehospitalization rate 6 months'
postprocedure compared with groups B and C (2.45 vs. 1.86 and 1.65, respectively;
P=0.05), nor reduced the mortality rate within the first year post-PEG placement
(75% vs. 58% and 38% for groups A, B, and C, respectively, P=0.001), as well, it
did not improve survival at 1 month after the procedure (15% vs. 3.26% and 7.76%,
for groups A, B, C, respectively, P<0.01). The presence of dementia was also
associated with shorter mean time to death (7.2 vs. 8.85 and 8 mo for groups A,
B, C, respectively, P<0.05). The rate of improvement of the nutritional biomarker
albumin was lower in the dementia group [3.1. to 2.9 vs. 3.2 to 3.3 and 3 to 3.3
g/dL for groups A, B, and C, respectively (P<0.02)]. Multivariate regression
analysis showed that the presence of dementia was an independent predictor for
mortality rate within the first year and 1-month mortality rate in patients
undergoing PEG insertion with odds ratio 3.22 (95% confidence interval, 1.52
4.32) and odds ratio 2.52 (95% confidence interval, 1.22-3.67). CONCLUSIONS: PEG
insertion in patients with dementia neither improve both short-term and long-term
mortality nor rehospitalization rate as compared with patients who underwent PEG
placement for alternate indications such as other neurological diseases or head
and neck malignancy and even was associated with shorter time to death.
Furthermore, PEG insertion in patients with dementia did not improve albumin.
Therefore, careful selection of patients with dementia is warranted before PEG
placement weighing the risks and benefits on a personalized basis.
PMID- 27505402
TI - Value of Oral Proton Pump Inhibitors in Acute, Nonvariceal Upper Gastrointestinal
Bleeding: A Network Meta-Analysis.
AB - BACKGROUND: Intravenous (IV) proton pump inhibitors (PPI) are the standard
medical treatment in acute nonvariceal upper gastrointestinal bleeding (ANVGIB).
Optimal route of PPI delivery has been questioned. AIM: The aim was to perform a
systematic review and network meta-analysis for the endpoints of risk of
rebleeding, length of stay (LOS), surgery (ROS), mortality, and total units of
blood transfused (UBT) among trials evaluating acid suppressive medications in
ANVGIB. METHODS: A total of 39 studies using IV PPI drip, IV scheduled PPI, oral
PPI, H2-receptor antagonists, and placebo were identified. Network meta-analysis
was used for indirect comparisons and Bayesian Markov Chain Monte Carlo methods
for calculation of probability superiority. RESULTS: No difference was observed
between IV PPI drip and scheduled IV PPI for mortality (relative risk=1.11; 95%
credibility interval, 0.56-2.21), LOS (0.04, -0.49 to 0.44), ROS (1.27, 0.64
2.35) and risk of rebleeding within 72 hours, 1 week, and 1 month [(0.98, 0.48
1.95), (0.59, 0.13-2.03), (0.82, 0.28-2.16)]. Oral PPIs were as effective as IV
scheduled PPIs and IV PPI drip for LOS (0.22, -0.61 to 0.79 and 0.16, -0.56 to
0.80) and UBT (-0.25, -1.23 to 0.65 and -0.06, -0.71 to 0.65) and superior to IV
PPI drip for ROS (0.30, 0.10 to 0.78). CONCLUSION: Scheduled IV PPIs were as
effective as IV PPI drip for most outcomes. Oral PPIs were comparable to
scheduled IV for LOS and UBT and superior to IV PPI drip for ROS. Conclusions
should be tempered by low frequency endpoints such as ROS, but question the need
for IV PPI drip in ANVGIB.
PMID- 27505403
TI - Current Status of Immunotherapy Treatments for Pancreatic Cancer.
AB - Pancreatic cancer (PC) is a lethal disease representing the seventh most frequent
cause of death from cancer worldwide. Resistance of pancreatic tumors to current
treatments leads to disappointing survival rates, and more specific and effective
therapies are urgently needed. In recent years, immunotherapy has been proposed
as a promising approach to the treatment of PC, and encouraging results have been
published by various preclinical and clinical studies. This review provides an
overview of the latest developments in the immunotherapeutic treatment of PC and
summarizes the most recent and important clinical trials.
PMID- 27505404
TI - Factors Associated With Metachronous Gastric Cancer Development After Endoscopic
Submucosal Dissection for Early Gastric Cancer.
AB - GOALS: To clarify the factors associated with metachronous gastric cancer
development after endoscopic submucosal dissection (ESD) for early gastric
cancer. BACKGROUND: Patients who undergo ESD for early gastric cancer have an
appreciable risk of developing metachronous gastric cancer. However, there have
been few reports on the association between life style and the development of
such cancer. STUDY: Patients with early gastric cancer who underwent ESD at our
institution between 2003 and 2012 were enrolled. Metachronous gastric cancer was
defined as secondary gastric cancer detected >1 year after initial ESD. Factors,
including age, gender, body mass index, eradication of Helicobacter pylori,
cigarette smoking, drinking, and continuous use of a proton pump inhibitor,
associated with metachronous gastric cancer development were evaluated by Cox
proportional hazard regression analysis. RESULTS: A total of 539 patients with a
mean 53.6-month follow-up period were analyzed. The 5-year cumulative incidence
of secondary gastric cancer was 13.0%. Multivariate analysis exhibited that age
of 60 years and above [hazard ratio (95% confidence interval)=4.05 (1.23-13.4)]
and cigarette smoking [2.12 (1.19-3.78)] were independent risk factors for
metachronous gastric cancer development. Furthermore, >=20 pack-years of smoking
[1.51 (1.03-2.24)] was a significant risk factor with a dose-response
relationship (P for trend=0.042). There was no significant association between
Helicobacter pylori eradication and metachronous gastric cancer development.
CONCLUSIONS: This is the first study to demonstrate the detailed association
between cigarette smoking and metachronous gastric cancer development.
PMID- 27505405
TI - Alcohol-related genes show an enrichment of associations with a persistent
externalizing factor.
AB - Research using twins has found that much of the variability in externalizing
phenotypes-including alcohol and drug use, impulsive personality traits, risky
sex, and property crime-is explained by genetic factors. Nevertheless,
identification of specific genes and variants associated with these traits has
proven to be difficult, likely because individual differences in externalizing
are explained by many genes of small individual effect. Moreover, twin research
indicates that heritable variance in externalizing behaviors is mostly shared
across the externalizing spectrum rather than specific to any behavior. We use a
longitudinal, "deep phenotyping" approach to model a general externalizing factor
reflecting persistent engagement in a variety of socially problematic behaviors
measured at 11 assessment occasions spanning early adulthood (ages 18 to 28). In
an ancestrally homogenous sample of non-Hispanic Whites (N = 337), we then tested
for enrichment of associations between the persistent externalizing factor and a
set of 3,281 polymorphisms within 104 genes that were previously identified as
associated with alcohol-use behaviors. Next, we tested for enrichment among
domain-specific factors (e.g., property crime) composed of residual variance not
accounted for by the common factor. Significance was determined relative to
bootstrapped empirical thresholds derived from permutations of phenotypic data.
Results indicated significant enrichment of genetic associations for persistent
externalizing, but not for domain-specific factors. Consistent with twin research
findings, these results suggest that genetic variants are broadly associated with
externalizing behaviors rather than unique to specific behaviors. (PsycINFO
Database Record
PMID- 27505406
TI - Clinical and personality traits in emotional disorders: Evidence of a common
framework.
AB - Certain clinical traits (e.g., ruminative response style, self-criticism,
perfectionism, anxiety sensitivity, fear of negative evaluation, and thought
suppression) increase the risk for and chronicity of emotional disorders. Similar
to traditional personality traits, they are considered dispositional and
typically show high temporal stability. Because the personality and clinical
traits literatures evolved largely independently, connections between them are
not fully understood. We sought to map the interface between a widely studied set
of clinical and personality traits. Two samples (N = 385 undergraduates; N = 188
psychiatric outpatients) completed measures of personality traits, clinical
traits, and an interview-based assessment of emotional-disorder symptoms. First,
the joint factor structure of these traits was examined in each sample. Second,
structural equation modeling was used to clarify the effects of clinical traits
in the prediction of clinical symptoms beyond negative temperament. Third, the
incremental validity of clinical traits beyond a more comprehensive set of higher
order and lower-order personality traits was examined using hierarchical
regression. Clinical and personality traits were highly correlated and jointly
defined a 3-factor structure-Negative Temperament, Positive Temperament, and
Disinhibition-in both samples, with all clinical traits loading on the Negative
Temperament factor. Clinical traits showed modest but significant incremental
validity in explaining symptoms after accounting for personality traits. These
data indicate that clinical traits relevant to emotional disorders fit well
within the traditional personality framework and offer some unique contributions
to the prediction of psychopathology, but it is important to distinguish their
effects from negative temperament/neuroticism. (PsycINFO Database Record
PMID- 27505407
TI - Attentional bias temporal dynamics in remitted depression.
AB - Theory implicates attentional bias (AB) or dysregulated attentional processing of
emotional information in the recurrence of major depressive episodes. However,
empirical study of AB among remitted depressed patients is limited in scope and
has yielded mixed findings. Mixed findings may be accounted for by how the field
has conceptualized and thereby studied AB. We propose that a novel temporal
dynamic process perspective on AB may help disambiguate extant findings and
elucidate the nature of AB in remitted depression. Thus, we reexamined Dot Probe
data among remitted depressed patients (RMD; n = 328) and nondepressed controls
(NDC; n = 82) that previously yielded null effects when AB was quantified by
means of the traditional aggregated mean bias score (Vrijsen et al., 2014). We
reanalyzed data using a novel computational approach that extracts a series of
bias estimations from trial to trial (Zvielli, Bernstein, & Koster, 2015). Key
features of these dynamic process signals revealed moderate to excellent
reliability relative to the traditional aggregated mean bias scores. These
features of AB dynamics-specifically temporal variability in AB including AB
toward and away from emotional stimuli-were significantly elevated among RMDs
relative to NDCs. Moreover, among RMDs, a greater number of past depressive
episodes were associated with elevation in these features of AB dynamics. Effects
were not accounted for by residual depressive symptoms or social anxiety
symptoms. Findings indicate that dysregulation in attentional processing of
emotional information reflected in AB dynamics may be key to depression
vulnerability. (PsycINFO Database Record
PMID- 27505408
TI - The reciprocal predictive relationship between high-risk personality and
drinking: An 8-wave longitudinal study in early adolescents.
AB - In youth, maladaptive personality traits such as urgency (the tendency to act
rashly when highly emotional) predict early onset alcohol consumption. In adults,
maladaptive behaviors, including substance use, predict negative personality
change. This article reports on a test of hypothesized maladaptive, reciprocal
prediction between youth drinking and the trait of urgency. In a sample of 1,906
youth assessed every 6 months from the spring of 5th grade through the spring of
8th grade, and again in the spring of 9th grade, the authors found such
reciprocal prediction. Over each 6 month and then 12 month time lag, urgency
predicted increased subsequent drinking. In addition, over 6 of the 7 time lags,
drinking behavior predicted subsequent increases in urgency. During early
adolescence, maladaptive personality and dysfunctional behavior each led to
increases in the other. The results of this process include cyclically increasing
risk for youth drinking and may include increasing risk for the multiple
maladaptive behaviors predicted by the trait of urgency. (PsycINFO Database
Record
PMID- 27505409
TI - Theory of mind is not theory of emotion: A cautionary note on the Reading the
Mind in the Eyes Test.
AB - The ability to represent mental states (theory of mind [ToM]) is crucial in
understanding individual differences in social ability and social impairments
evident in conditions such as autism spectrum disorder (ASD). The Reading the
Mind in the Eyes Test (RMET) is a popular measure of ToM ability, validated in
part by the poor performance of those with ASD. However, the RMET requires
recognition of facial emotion, which is impaired in those with alexithymia, which
frequently co-occurs with ASD. Thus, it is unclear whether the RMET indexes
emotion recognition, associated with alexithymia, or ToM, associated with ASD. We
therefore investigated the independent contributions of ASD and alexithymia to
performance on the RMET. ASD and alexithymia-matched control participants did not
differ on RMET performance, whereas ASD participants demonstrated impaired
performance on an alternative test of ToM, the Movie for Assessment of Social
Cognition (MASC). Furthermore, alexithymia, but not ASD diagnosis, significantly
influenced RMET performance but did not affect MASC performance. These results
suggest that the RMET measures emotion recognition rather than ToM ability and
support the alexithymia hypothesis of emotion-related deficits in ASD. (PsycINFO
Database Record
PMID- 27505410
TI - Chemical Constituents Isolated from Bletilla striata and Their Inhibitory Effects
on Nitric Oxide Production in RAW 264.7 Cells.
AB - Bioassay-guided fractionation of the MeOH extract of the tubers of Bletilla
striata led to the isolation of two new C-methylated flavan-3-ols, bletillanols A
(1) and B (2), along with ten known compounds (3 - 12). Their structures were
determined by using extensive spectroscopic analysis including 1D-, 2D-NMR, and
circular dichroism data. All of the isolated compounds were tested for their
inhibitory potential on the nitric oxide generation in LPS-stimulated RAW 264.7
cells.
PMID- 27505411
TI - Second-Order Systematicity of Associative Learning: A Paradox for Classical
Compositionality and a Coalgebraic Resolution.
AB - Systematicity is a property of cognitive architecture whereby having certain
cognitive capacities implies having certain other "structurally related"
cognitive capacities. The predominant classical explanation for systematicity
appeals to a notion of common syntactic/symbolic structure among the
systematically related capacities. Although learning is a (second-order)
cognitive capacity of central interest to cognitive science, a systematic ability
to learn certain cognitive capacities, i.e., second-order systematicity, has been
given almost no attention in the literature. In this paper, we introduce learned
associations as an instance of second-order systematicity that poses a paradox
for classical theory, because this form of systematicity involves the kinds of
associative constructions that were explicitly rejected by the classical
explanation. Our category theoretic explanation of systematicity resolves this
problem, because both first and second-order forms of systematicity are derived
from the same categorical construction: universal morphisms, which generalize the
notion of compositionality of constituent representations to (categorical)
compositionality of constituent processes. We derive a model of systematic
associative learning based on (co)recursion, which is an instance of a universal
construction. These results provide further support for a category theory
foundation for cognitive architecture.
PMID- 27505412
TI - Role for Torsin in Lipid Metabolism.
AB - DYT1 dystonia is a neurological disease that causes involuntary twisting
movements, often caused by dysfunction of the TorsinA gene. In this issue of
Developmental Cell, Grillet et al. (2016) use Drosophila to discover that TorsinA
regulates lipid metabolism, opening up future directions of research into the
causes of this disease.
PMID- 27505413
TI - Of Mice and Snakes: A Tail of Oct4.
AB - The vertebrate axial skeleton comprises regions of specialized vertebrae, which
vary in length between lineages. Aires et al. (2016) uncover a key role for Oct4
in determining trunk length in mice. Additionally, a heterochronic shift in Oct4
expression may underlie the extreme elongation of the trunk in snakes.
PMID- 27505414
TI - Keratins Are Going Nuclear.
AB - Previously thought to reside exclusively in the cytoplasm, the cytoskeletal
protein keratin 17 (K17) has been recently identified inside the nucleus of tumor
epithelial cells with a direct impact on cell proliferation and gene expression.
We comment on fundamental questions raised by this new finding and the associated
significance.
PMID- 27505415
TI - Nonrandom Germline Transmission of Mouse Spermatogonial Stem Cells.
AB - Genes are thought to be transmitted to offspring by random fertilization of a
small number of oocytes with numerous spermatozoa. Here we analyzed the dynamics
of male germline transmission by genetic marking and transplantation of
spermatogonial stem cells (SSCs). We found that offspring deriving from a small
number of specific SSCs appear within a limited time. Interestingly, the same SSC
clones reappear later with an average functional lifespan of ~124.4 days. Cyclic
offspring production from SSCs was not caused by changes in SSC self-renewal
activity because lineage-tracing analyses suggested that all SSCs actively
proliferated. Selection appears to occur during the differentiating spermatogonia
stage, when extensive apoptosis was observed. The pattern of germline
transmission could be predicted using a mathematical model in which SSCs repeat
cycles of transient spermatogenic burst and refractory periods. Thus,
spermatogenesis is a regulated process whereby specific SSC clones are repeatedly
recruited for fertilization with long-term cycles.
PMID- 27505416
TI - Adhesion and Fusion of Muscle Cells Are Promoted by Filopodia.
AB - Indirect flight muscles (IFMs) in Drosophila are generated during pupariation by
fusion of hundreds of myoblasts with larval muscle templates (myotubes). Live
observation of these muscles during the fusion process revealed multiple long
actin-based protrusions that emanate from the myotube surface and require Enabled
and IRSp53 for their generation and maintenance. Fusion is blocked when formation
of these filopodia is compromised. While filopodia are not required for the
signaling process underlying critical myoblast cell-fate changes prior to fusion,
myotube-myoblast adhesion appears to be filopodia dependent. Without filopodia,
close apposition between the cell membranes is not achieved, the cell-adhesion
molecule Duf is not recruited to the myotube surface, and adhesion-dependent
actin foci do not form. We therefore propose that the filopodia are necessary to
prime the heterotypic adhesion process between the two cell types, possibly by
recruiting the cell-adhesion molecule Sns to discrete patches on the myoblast
cell surface.
PMID- 27505417
TI - Protocadherin-17 Mediates Collective Axon Extension by Recruiting Actin Regulator
Complexes to Interaxonal Contacts.
PMID- 27505418
TI - Involving High School Students in Computational Physics University Research:
Theory Calculations of Toluene Adsorbed on Graphene.
AB - To increase public awareness of theoretical materials physics, a small group of
high school students is invited to participate actively in a current research
projects at Chalmers University of Technology. The Chalmers research group
explores methods for filtrating hazardous and otherwise unwanted molecules from
drinking water, for example by adsorption in active carbon filters. In this
project, the students use graphene as an idealized model for active carbon, and
estimate the energy of adsorption of the methylbenzene toluene on graphene with
the help of the atomic-scale calculational method density functional theory. In
this process the students develop an insight into applied quantum physics, a
topic usually not taught at this educational level, and gain some experience with
a couple of state-of-the-art calculational tools in materials research.
PMID- 27505419
TI - A Cost-Effective Approach to Sequence Hundreds of Complete Mitochondrial Genomes.
AB - We present a cost-effective approach to sequence whole mitochondrial genomes for
hundreds of individuals. Our approach uses small reaction volumes and unmodified
(non-phosphorylated) barcoded adaptors to minimize reagent costs. We demonstrate
our approach by sequencing 383 Fundulus sp. mitochondrial genomes (192 F.
heteroclitus and 191 F. majalis). Prior to sequencing, we amplified the
mitochondrial genomes using 4-5 custom-made, overlapping primer pairs, and
sequencing was performed on an Illumina HiSeq 2500 platform. After removing low
quality and short sequences, 2.9 million and 2.8 million reads were generated for
F. heteroclitus and F. majalis respectively. Individual genomes were assembled
for each species by mapping barcoded reads to a reference genome. For F. majalis,
the reference genome was built de novo. On average, individual consensus
sequences had high coverage: 61-fold for F. heteroclitus and 57-fold for F.
majalis. The approach discussed in this paper is optimized for sequencing
mitochondrial genomes on an Illumina platform. However, with the proper
modifications, this approach could be easily applied to other small genomes and
sequencing platforms.
PMID- 27505420
TI - Automated Texture Analysis and Determination of Fibre Orientation of Heart
Tissue: A Morphometric Study.
AB - The human heart has a heterogeneous structure, which is characterized by
different cell types and their spatial configurations. The physical structure,
especially the fibre orientation and the interstitial fibrosis, determines the
electrical excitation and in further consequence the contractility in macroscopic
as well as in microscopic areas. Modern image processing methods and parameters
could be used to describe the image content and image texture. In most cases the
description of the texture is not satisfying because the fibre orientation,
detected with common algorithms, is biased by elements such as fibrocytes or
endothelial nuclei. The goal of this work is to figure out if cardiac tissue can
be analysed and classified on a microscopic level by automated image processing
methods with a focus on an accurate detection of the fibre orientation.
Quantitative parameters for identification of textures of different complexity or
pathological attributes inside the heart were determined. The focus was set on
the detection of the fibre orientation, which was calculated on the basis of the
cardiomyocytes' nuclei. It turned out that the orientation of these nuclei
corresponded with a high precision to the fibre orientation in the image plane.
Additionally, these nuclei also indicated very well the inclination of the fibre.
PMID- 27505421
TI - Highly Conductive Anion-Exchange Membranes from Microporous Troger's Base
Polymers.
AB - The development of polymeric anion-exchange membranes (AEMs) combining high ion
conductivity and long-term stability is a major challenge for materials
chemistry. AEMs with regularly distributed fixed cationic groups, based on the
formation of microporous polymers containing the V-shape rigid Troger's base
units, are reported for the first time. Despite their simple preparation, which
involves only two synthetic steps using commercially available precursors, the
polymers provide AEMs with exceptional hydroxide conductivity at relatively low
ion-exchange capacity, as well as a high swelling resistance and chemical
stability. An unprecedented hydroxide conductivity of 164.4 mS cm(-1) is obtained
at a relatively a low ion-exchange capacity of 0.82 mmol g(-1) under optimal
operating conditions. The exceptional anion conductivity appears related to the
intrinsic microporosity of the charged polymer matrix, which facilitates rapid
anion transport.
PMID- 27505422
TI - Vitamin D3 Partly Antagonizes Advanced-Glycation Endproducts-Induced NFkappaB
Activation in Mouse Podocytes.
AB - BACKGROUND/AIMS: We have previously shown that advanced glycation-endproducts
(AGEs) induced NFkappaB activation in differentiated mouse podocytes. This
NFkappaB activation may contribute to the progression of renal disease and
mediation of fibrosis by various mechanisms. This study was undertaken to test
whether this detrimental response may be reversed by vitamin D3 or its analogue
paricalcitol. METHODS: Differentiated mouse podocytes were challenged with
glycated bovine serum albumin (AGE-BSA), or non-glycated control BSA (in the
presence or absence of various concentrations of vitamin D3 (decostriol,
1alpha,25-dihydroxyvitamin D3)) or its active analog paricalcitol. Quantitative
mRNA expressions were measured by real-time PCR, whereas protein expressions were
determined by Western blotting followed by densitometry. Cytoplasmic and nuclear
protein expression of the NFkappaB subunit p65 (Rel A) were determined by Western
blotting. Furthermore, the ratio of phosphorylated to non-phosphorylated IkappaB
alpha was measured using specific antibodies. Electrophoretic mobility shift
assays and a capture ELISA assay were used to assess NFkappaB transactivation in
vitro. In addition, NFkappaB transactivation was also monitored in HEK-NFkappaBIA
reporter cells using live cell luminometry. RESULTS: Podocytes expressed the
receptor for vitamin D. The vitamins did not suppress receptor for AGEs (RAGE)
expression; instead, they rather upregulated RAGE. Although vitamin D3 and
paricalcitol partly and differentially modified some of the studied parameters,
both hormones inhibited AGE-BSA-induced NFkappaB transactivation, presumably by
various mechanisms including the upregulation of IkappaB-alpha protein, keeping
NFkappaB sequestered in an inactive state in the cytoplasm. CONCLUSION: Vitamin
D3 or its analog paricalcitol partly prevented AGE-mediated NFkappaB activation,
an important feature of diabetic nephropathy (DN). Whether this in vitro finding
is of clinical relevance to prevent/treat DN requires further studies.
PMID- 27505423
TI - Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction
in Rats.
AB - Intestinal microbiota determine severity of myocardial infarction in rats. We
determined whether low molecular weight metabolites derived from intestinal
microbiota and transported to the systemic circulation are linked to severity of
myocardial infarction. Plasma from rats treated for seven days with the non
absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin
B and bacitracin was analyzed using mass spectrometry-based metabolite profiling
platforms. Antibiotic-induced changes in the abundance of individual groups of
intestinal microbiota dramatically altered the host's metabolism. Hierarchical
clustering of dissimilarities separated the levels of 284 identified metabolites
from treated vs. untreated rats; 193 were altered by the antibiotic treatments
with a tendency towards decreased metabolite levels. Catabolism of the aromatic
amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway
comprising 33 affected metabolites. Both antibiotic treatments decreased the
severity of an induced myocardial infarction in vivo by 27% and 29%,
respectively. We then determined whether microbial metabolites of the amino acids
phenylalanine, tryptophan and tyrosine were linked to decreased severity of
myocardial infarction. Vancomycin-treated rats were administered amino acid
metabolites prior to ischemia/reperfusion studies. Oral or intravenous
pretreatment of rats with these amino acid metabolites abolished the decrease in
infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 MUM), Src
kinase (PP1, 20 MUM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059,
10 MUM), p38 MAPK (SB203580, 10 MUM), or KATP channels (glibenclamide, 3 MUM)
abolished cardioprotection by vancomycin, indicating microbial metabolites are
interacting with cell surface receptors to transduce their signals through Src
kinase, cell survival pathways and KATP channels. These inhibitors have no effect
on myocardial infarct size in untreated rats. This study links gut microbiota
metabolites to severity of myocardial infarction and may provide future
opportunities for novel diagnostic tests and interventions for the prevention of
cardiovascular disease.
PMID- 27505424
TI - Switching Away from Utilitarianism: The Limited Role of Utility Calculations in
Moral Judgment.
AB - Our moral motivations might include a drive towards maximizing overall welfare,
consistent with an ethical theory called "utilitarianism." However, people show
non-utilitarian judgments in domains as diverse as healthcare decisions, income
distributions, and penal laws. Rather than these being deviations from a
fundamentally utilitarian psychology, we suggest that our moral judgments are
generally non-utilitarian, even for cases that are typically seen as
prototypically utilitarian. We show two separate deviations from utilitarianism
in such cases: people do not think maximizing welfare is required (they think it
is merely acceptable, in some circumstances), and people do not think that equal
welfare tradeoffs are even acceptable. We end by discussing how utilitarian
reasoning might play a restricted role within a non-utilitarian moral psychology.
PMID- 27505426
TI - The cytotoxic T lymphocyte immune synapse at a glance.
AB - The immune synapse provides an important structure for communication with immune
cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs)
highlight the dynamic changes and specialised mechanisms required to facilitate
focal signalling and polarised secretion in immune cells. In this Cell Science at
a Glance article and the accompanying poster, we illustrate the different steps
that reveal the specialised mechanisms used to focus secretion at the CTL immune
synapse and allow CTLs to be such efficient and precise serial killers.
PMID- 27505427
TI - Regulation of myogenesis by environmental hypoxia.
AB - In aerobic organisms, oxygen is a critical factor for tissue and organ
morphogenesis from embryonic development throughout the adult life. It regulates
various intracellular pathways involved in cellular metabolism, proliferation,
cell survival and fate. Organisms or tissues rapidly respond to changes in oxygen
availability by activating complex signalling networks, which culminate in the
control of mRNA translation and/or gene expression. This Commentary presents the
effects of hypoxia during embryonic development, myoblasts and satellite cell
proliferation and differentiation in vertebrates. We also outline the
relationship between Notch, Wnt and growth factor signalling pathways, as well as
the post-transcriptional regulation of myogenesis under conditions of hypoxia.
PMID- 27505429
TI - The role of palmitoylation and transmembrane domain in sorting of transmembrane
adaptor proteins.
PMID- 27505428
TI - Molecular organization of the desmosome as revealed by direct stochastic optical
reconstruction microscopy.
AB - Desmosomes are macromolecular junctions responsible for providing strong cell
cell adhesion. Because of their size and molecular complexity, the precise
ultrastructural organization of desmosomes is challenging to study. Here, we used
direct stochastic optical reconstruction microscopy (dSTORM) to resolve
individual plaque pairs for inner and outer dense plaque proteins. Analysis
methods based on desmosomal mirror symmetry were developed to measure plaque-to
plaque distances and create an integrated map. We quantified the organization of
desmoglein 3, plakoglobin and desmoplakin (N-terminal, rod and C-terminal
domains) in primary human keratinocytes. Longer desmosome lengths correlated with
increasing plaque-to-plaque distance, suggesting that desmoplakin is arranged
with its long axis at an angle within the plaque. We next examined whether plaque
organization changed in different adhesive states. Plaque-to-plaque distance for
the desmoplakin rod and C-terminal domains decreased in PKP-1-mediated
hyperadhesive desmosomes, suggesting that protein reorganization correlates with
function. Finally, in human epidermis we found a difference in plaque-to-plaque
distance for the desmoplakin C-terminal domain, but not the desmoplakin rod
domain or plakoglobin, between basal and suprabasal cells. Our data reveal the
molecular organization of desmosomes in cultured keratinocytes and skin as
defined by dSTORM.
PMID- 27505430
TI - Bok is a genuine multi-BH-domain protein that triggers apoptosis in the absence
of Bax and Bak.
PMID- 27505432
TI - Real-Life Study for the Diagnosis of House Dust Mite Allergy - The Value of
Recombinant Allergen-Based IgE Serology.
AB - BACKGROUND: Dermatophagoides pteronyssinus is one of the most important perennial
allergen sources worldwide. Molecular diagnostics using the commercially
available major allergens (Der p 1 and Der p 2) in combination with Der p 10 do
not detect house dust mite (HDM) sensitization in a number of cases when used
alone. The objective was to evaluate the IgE reactivity profiles of these
patients using an experimental immunoassay biochip. METHODS: Sera of HDM-allergic
patients (positive skin prick test, CAP class >=1 for allergen extract, and
positive intranasal provocation) were tested for IgE antibodies against Der p 1,
Der p 2, and Der p 10 by ImmunoCAP fluorescence enzyme immunoassay. Negatively
tested sera were examined by an experimental chip containing 13 microarrayed HDM
allergens. RESULTS: Of 97 patients tested, 16 showed negative results to Der p 1,
Der p 2, and Der p 10. MeDALL chip evaluation revealed 5 patients monosensitized
to Der p 23, and 11 patients were negative for all HDM MeDALL chip components.
Seven sera were available for further testing, and 3 of them showed IgE
reactivity to dot-blotted nDer p 1, and 2 reacted with high-molecular weight
components (>100 kDa) in nitrocellulose-blotted HDM extract when tested with 125I
labeled anti-IgE in a RAST-based assay. The HDM extract-specific IgE levels of
the 11 patients were <3.9 kU/l. CONCLUSIONS: Recombinant allergen-based IgE
serology is of great value when conventional IgE diagnostics fails. Der p 23 is
an important HDM allergen, especially when major allergens are negative.
Therefore, it would be desirable to have Der p 23 commercially available. Further
research concerning the prevalence and clinical significance of different HDM
allergens is needed.
PMID- 27505431
TI - Epigenetics of Epileptogenesis-Evoked Upregulation of Matrix Metalloproteinase-9
in Hippocampus.
AB - Enhanced levels of Matrix Metalloproteinase-9 (MMP-9) have been implicated in the
pathogenesis of epilepsy in humans and rodents. Lack of Mmp-9 impoverishes,
whereas excess of Mmp-9 facilitates epileptogenesis. Epigenetic mechanisms
driving the epileptogenesis-related upregulation of MMP-9 expression are
virtually unknown. The aim of this study was to reveal these mechanisms. We
analyzed hippocampi extracted from adult and pediatric patients with temporal
lobe epilepsy as well as from partially and fully pentylenetetrazole kindled
rats. We used a unique approach to the analysis of the kindling model results
(inclusion in the analysis of rats being during kindling, and not only a group of
fully kindled animals), which allowed us to separate the molecular effects
exerted by the epileptogenesis from those related to epilepsy and epileptic
activity. Consequently, it allowed for a disclosure of molecular mechanisms
underlying causes, and not consequences, of epilepsy. Our data show that the
epileptogenesis-evoked upregulation of Mmp-9 expression is regulated by removal
from Mmp-9 gene proximal promoter of the two, interweaved potent silencing
mechanisms-DNA methylation and Polycomb Repressive Complex 2 (PRC2)-related
repression. Demethylation depends on a gradual dissociation of the DNA
methyltransferases, Dnmt3a and Dnmt3b, and on progressive association of the DNA
demethylation promoting protein Gadd45beta to Mmp-9 proximal gene promoter in
vivo. The PRC2-related mechanism relies on dissociation of the repressive
transcription factor YY1 and the dissipation of the PRC2-evoked trimethylation on
Lys27 of the histone H3 from the proximal Mmp-9 promoter chromatin in vivo.
Moreover, we show that the DNA hydroxymethylation, a new epigenetic DNA
modification, which is localized predominantly in the gene promoters and is
particularly abundant in the brain, is not involved in a regulation of MMP-9
expression during the epileptogenesis in the rat hippocampus as well as in the
hippocampi of pediatric and adult epileptic patients. Additionally, we have also
found that despite of its transient nature, the histone modification H3S10ph is
strongly and gradually accumulated during epileptogenesis in the cell nuclei and
in the proximal Mmp-9 gene promoter in the hippocampus, which suggests that
H3S10ph can be involved in DNA demethylation in mammals, and not only in
Neurospora. The study identifies MMP-9 as the first protein coding gene which
expression is regulated by DNA methylation in human epilepsy. We present a
detailed epigenetic model of the epileptogenesis-evoked upregulation of MMP-9
expression in the hippocampus. To our knowledge, it is the most complex and most
detailed mechanism of epigenetic regulation of gene expression ever revealed for
a particular gene in epileptogenesis. Our results also suggest for the first time
that dysregulation of DNA methylation found in epilepsy is a cause rather than a
consequence of this condition.
PMID- 27505433
TI - Rapid, in Situ Synthesis of High Capacity Battery Anodes through High Temperature
Radiation-Based Thermal Shock.
AB - High capacity battery electrodes require nanosized components to avoid
pulverization associated with volume changes during the charge-discharge process.
Additionally, these nanosized electrodes need an electronically conductive matrix
to facilitate electron transport. Here, for the first time, we report a rapid
thermal shock process using high-temperature radiative heating to fabricate a
conductive reduced graphene oxide (RGO) composite with silicon nanoparticles.
Silicon (Si) particles on the order of a few micrometers are initially embedded
in the RGO host and in situ transformed into 10-15 nm nanoparticles in less than
a minute through radiative heating. The as-prepared composites of ultrafine Si
nanoparticles embedded in a RGO matrix show great performance as a Li-ion battery
(LIB) anode. The in situ nanoparticle synthesis method can also be adopted for
other high capacity battery anode materials including tin (Sn) and aluminum (Al).
This method for synthesizing high capacity anodes in a RGO matrix can be
envisioned for roll-to-roll nanomanufacturing due to the ease and scalability of
this high-temperature radiative heating process.
PMID- 27505434
TI - Chromosome Territory Modeller and Viewer.
AB - This paper presents ChroTeMo, a tool for chromosome territory modelling,
accompanied by ChroTeVi-a chromosome territory visualisation software that uses
the data obtained by ChroTeMo. These tools have been developed in order to
complement the molecular cytogenetic research of interphase nucleus structure in
a model grass Brachypodium distachyon. Although the modelling tool has been
initially created for one particular species, it has universal application. The
proposed version of ChroTeMo allows for generating a model of chromosome
territory distribution in any given plant or animal species after setting the
initial, species-specific parameters. ChroTeMo has been developed as a fully
probabilistic modeller. Due to this feature, the comparison between the
experimental data on the structure of a nucleus and the results obtained from
ChroTeMo can indicate whether the distribution of chromosomes inside a nucleus is
also fully probabilistic or is subjected to certain non-random patterns. The
presented tools have been written in Python, so they are multiplatform, portable
and easy to read. Moreover, if necessary they can be further developed by users
writing their portions of code. The source code, documentation, and wiki, as well
as the issue tracker and the list of related articles that use ChroTeMo and
ChroTeVi, are accessible in a public repository at Github under GPL 3.0 license.
PMID- 27505435
TI - The Prognostic Value of a Four-Dimensional CT Angiography-Based Collateral
Grading Scale for Reperfusion Therapy in Acute Ischemic Stroke Patients.
AB - OBJECTIVE: Leptomeningeal collaterals, which affects tissue fate, are still
challenging to assess. Four-dimensional CT angiography (4D CTA) originated from
CT perfusion (CTP) provides the possibility of non-invasive and time-resolved
assessment of leptomeningeal collateral flow. We sought to develop a
comprehensive rating system to integrate the speed and extent of collateral flow
on 4D CTA, and investigate its prognostic value for reperfusion therapy in acute
ischemic stroke (AIS) patients. METHODS: We retrospectively studied 80 patients
with M1 +/- internal carotid artery (ICA) occlusion who had baseline CTP before
intravenous thrombolysis. The velocity and extent of collaterals were evaluated
by regional leptomeningeal collateral score on peak phase (rLMC-P) and temporally
fused intensity projections (tMIP) (rLMC-M) on 4D CTA, respectively. The cutoffs
of rLMC-P and rLMC-M score for predicting good outcome (mRS score <= 2) were
integrated to develop the collateral grading scale (CGS) (rating from 0-2).
RESULTS: The CGS score was correlated with 3-months mRS score (non-recanalizers:
rho = -0.495, p = 0.01; recanalizers: rho = -0.671, p < 0.001). Patients with
intermediate or good collaterals (CGS score of 1 and 2) who recanalized were more
likely to have good outcome than those without recanalization (p = 0.038, p =
0.018), while there was no significant difference in outcome in patients with
poor collaterals (CGS score of 0) stratified by recanalization (p = 0.227).
CONCLUSIONS: Identification of collaterals based on CGS may help to select good
responders to reperfusion therapy in patients with large artery occlusion.
PMID- 27505436
TI - Total Synthesis of the Resorcyclic Acid Lactone Spiroketal Citreoviranol.
AB - The first total synthesis of resorcyclic acid lactone spiroketal citreoviranol
(1) is described. The synthesis was completed in nine steps and via Sonogashira
cross-coupling, gold-catalyzed cyclization, and an unusual base-induced
ketalization. The relative and absolute stereochemistry of citreoviranol was
unambiguously confirmed using 2D NMR spectroscopy and X-ray crystallography.
PMID- 27505437
TI - Saguaro (Carnegiea gigantea) Mortality and Population Regeneration in the Cactus
Forest of Saguaro National Park: Seventy-Five Years and Counting.
AB - Annual census data spanning seventy-five years document mortality and
regeneration in a population of saguaro cactus (Carnegiea gigantea) in the Cactus
Forest of the Rincon Mountain District of Saguaro National Park near Tucson, AZ.
On 6 four-hectare plots, each saguaro was censused and a methodical search for
new saguaros was conducted annually each year from 1942 through 2016, with the
exception of 1955. Regeneration has been episodic with 828 plants established
from 1959 through 1993 compared with 34 plants established between 1942 and 1958
and only three plants established after 1993. The years preceding 1959 and
following 1993, include some of the driest decades in centuries in southern
Arizona. While woodcutting and cattle grazing are believed to be among the causes
of decades of failed regeneration prior to 1958, neither of these factors
contributed to the failed regeneration following 1993. The height structure of
the population from 1942 to 2016 shifted dramatically from a population dominated
by large saguaros (> 5.4 m tall) in the first three decades of the study to a
population dominated by small saguaros (< 1.8 m tall) in the most recent two
decades. Mortality is shown to be strongly age dependent. In the year following
the 2011 catastrophic freeze, 21 of 59 plants older than 80 years died compared
with zero deaths in 270 plants between the ages of 29 and 80 years. Saguaros
under 40 years old, growing under small shrubs or in the open, have a lower
probability of survival than better protected saguaros. Long-term population
monitoring is essential to understanding the complex impacts of human and
environmental factors on the population dynamics of long-lived species.
PMID- 27505438
TI - Re: Carrier Screening is a Deficient Strategy for Determining Sperm Donor
Eligibility and Reducing Risk of Disease in Recipient Children (From: Silver AJ,
Larson JL, Silver MJ, et al. Genet Test Mol Biomarkers 2016;20:276-284).
PMID- 27505439
TI - Authors' Response to Wong et al.
PMID- 27505440
TI - A large single ethnicity study of prepulse inhibition in schizophrenia: Separate
analysis by sex focusing on effect of symptoms.
AB - Deficits in sensorimotor gating, as measured with prepulse inhibition (PPI), have
been considered an endophenotype of schizophrenia. However, the question remains
whether these deficits are related to current symptoms. This single site study
aimed to explore clinical features related to the modulation of startle reflex in
a large sample of Japanese patients with schizophrenia (DSM-IV). The subjects
comprised 181 patients and 250 healthy controls matched for age and sex.
Schizophrenia symptoms were assessed with the Positive and Negative Syndrome
Scale (PANSS). Startle reflex to acoustic stimuli was recorded using a startle
stimulus of 115 dB and a prepulse of four different conditions (intensity: 86 dB
or 90 dB; lead interval: 60 ms or 120 ms). Patients exhibited significantly
reduced startle magnitude (p < 0.001), habituation (p = 0.001), and PPI (90 dB,
60 ms, p = 0.016; 90 dB, 120 ms, p = 0.001) compared with controls. Patients of
both sexes exhibited significantly lower habituation and PPI (90 dB, 120 ms)
compared with the same sex controls. We could not detect a significant
correlation with any clinical variable in the entire patients, however, when men
and women were examined separately, there was a negative correlation with the
PANSS cognitive domain (rho = -0.33, p = 0.008) in men, but not in women.
Moreover, when patients were subdivided into four clusters, two clusters with
high positive symptoms showed significant PPI deficits in men. Our results
suggest that sensorimotor gating is impaired in schizophrenia of both sexes, and
PPI deficits may be related to thought disturbance and disorganization in male
patients with schizophrenia.
PMID- 27505441
TI - Discovery, Synthesis, and Evaluation of 2,4-Diaminoquinazolines as a Novel Class
of Pancreatic beta-Cell-Protective Agents against Endoplasmic Reticulum (ER)
Stress.
AB - Pancreatic insulin-producing beta-cell dysfunction and death plays central roles
in the onset and progression of both type 1 and type 2 diabetes. Current
antidiabetic drugs cannot halt the ongoing progression of beta-cell dysfunction
and death. In diabetes, a major cause for the decline in beta-cell function and
survival is endoplasmic reticulum (ER) stress. Here, we identified quinazoline
derivatives as a novel class of beta-cell protective agents against ER stress
induced dysfunction and death. A series of quinazoline derivatives were
synthesized from dichloroquiazoline utilizing a sequence of nucleophilic
reactions. Through SAR optimization, 2,4-diaminoquinazoline compound 9c markedly
protects beta-cells against ER stress-induced dysfunction and death with 80%
maximum rescue activity and an EC50 value of 0.56 MUM. Importantly, 9c restores
the ER stress-impaired glucose-stimulated insulin secretion response and survival
in primary human islet beta-cells. We showed that 9c protects beta-cells by
alleviating ER stress through the suppression of the induction of key genes of
the unfolded protein response and apoptosis.
PMID- 27505442
TI - Bacterial Light-Harvesting Complexes Showing Giant Second-Order Nonlinear Optical
Response as Revealed by Hyper-Rayleigh Light Scattering.
AB - The second-order nonlinear optical (NLO) properties of light-harvesting complexes
(LHs) from the purple photosynthetic bacteria Thermochromatium (Tch.) tepidum
were investigated for the first time by means of hyper-Rayleigh scattering (HRS).
The carotenoid (Car) molecules bound to the isolated LH1 and LH2 proteins gave
rise to second-harmonic scattering; however, they showed an opposite effect of
the collective contribution from Car, that is, the first hyperpolarizability
(beta) reduced substantially from (10 510 +/- 370) * 10(-30) esu for LH1 to (360
+/- 120) * 10(-30) esu for LH2. Chromatophores of Tch. tepidum also showed a
giant hyperpolarizability of (11 640 +/- 630) * 10(-30) esu. On the basis of the
structural information on bacterial LHs, it is found that the effective beta of
an LH is governed by the microenvironment and orientational correlation among the
Car chromophores, which is concluded to be coherently enhanced for LH1. For LH2,
however, additional destructive effects between different Car molecules may
account for the small beta value. This work demonstrates that LH1 and native
membranes of purple bacteria can be potent NLO materials and that HRS is a
promising spectroscopic means for investigating structural information of pigment
protein supramolecules.
PMID- 27505443
TI - Prevalence and Factors Associated With Statin Use Among a Nationally
Representative Sample of US Adults: National Health and Nutrition Examination
Survey, 2011-2012.
AB - The 2013 American College of Cardiology/American Heart Association guidelines
recommend statins for adults age <=75 years who have clinical atherosclerotic
cardiovascular disease (IA) and adults age 40 to 75 years with diabetes mellitus
and LDL-C 70-189 mg/dl (IA). Our aim was to estimate the prevalence and
likelihood of statin use among selected statin benefit groups. Using data from
the National Health and Nutrition Examination Survey (NHANES) 2011-2012, we
examined 5319 adults age >=20 years. We estimated weighted frequencies and
prevalence of statin use for adults with diabetes mellitus and dyslipidemia (or
low-density lipoprotein cholesterol >=70 mg/dL), defined as statin benefit group
1 (SBG1); and for adults with atherosclerotic cardiovascular disease, defined as
statin benefit group 2 (SBG2). We constructed a logistic regression model to
estimate odds of statin use in SBG1. Overall, an estimated 38.6 million Americans
are on a statin. In adjusted models, uninsured and Hispanic adults were less
likely to be on a statin compared with white adults; 59.5% (95% confidence
interval [CI]: 53.0-66.1) of all adults in SBG1, 58.8% (95% CI: 51.5-66.1) of
adults age 40 to 75 in SBG1, and 63.5% (95% CI: 55.6-71.4) of all adults in SBG2
were on a statin. Although the prevalence of statin use has increased over time,
Hispanic ethnicity and lack of insurance remain barriers to statin use. Black
white racial disparities were not significant. Our study provides a baseline
estimate of statin use in the noninstitutionalized population just prior to
introduction of the new guidelines and provides a reference for evaluating the
impact of the new guidelines on statin utilization.
PMID- 27505444
TI - Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub
Saharan Africa: An Operations Research Agenda.
AB - Sydney Rosen and colleagues describe an operations research agenda to
accelerating uptake of HIV treatment initiation.
PMID- 27505445
TI - Plasmachemical Double Click Thiol-ene Reactions for Wet Electrical Barrier.
AB - Click thiol-ene chemistry is demonstrated for the reaction of thiol containing
molecules with surface alkene bonds during electrical discharge activation. This
plasmachemical reaction mechanism is shown to be 2-fold for allyl mercaptan (an
alkene and thiol group containing precursor), comprising self-cross-linked
nanolayer deposition in tandem with interfacial cross-linking to the surface
alkene bonds of a polyisoprene base layer. A synergistic multilayer structure is
attained which displays high wet electrical barrier performance during immersion
in water.
PMID- 27505446
TI - Novel mouse model for primary uveal melanoma: a pilot study.
AB - BACKGROUND: To establish a mouse model with the aim of studying the tumour
biology and metastasis formation of uveal melanoma. METHODS: Two human primary
uveal melanoma cell lines (UMT2 and UMT42) were injected into the choroid of
BALB/c nude mouse eyes. Intraocular tumour growth and metastasis formation in the
liver and lungs were assessed after 13 to 22 weeks. Formalin-fixed, paraffin
embedded material was processed via haematoxylin and eosin staining for
histological examination and periodic acid Schiff staining to search for
extravascular matrix patterns. Immunohistochemistry for Melan A, CD34 and Ki67
was performed to assess the expression of a melanocytic lineage marker,
angiogenesis and proliferative activity. RESULTS: All eyes injected with UMT2
cells, but only 25% of eyes treated with UMT42, developed intraocular tumour
growth. The morphology of intraocular melanomas resembled that of primary tumours
and showed signs of malignancy, including retinal invasion, optic nerve invasion
and scleral penetration with extraocular tumour growth. UMT2 tumours formed
extravascular matrix patterns exclusively. Most of the tumour cells expressed
Melan A. Intratumoural angiogenesis was detected in both tumour entities.
Proliferative activity was verified in all but one tumour. However, no metastases
appeared in the liver or lungs. CONCLUSIONS: The mouse model presented with the
UMT2 cell line allows for investigations of tumour biology of the primary UM
because of the high degree of similarity between the tumours generated in the
mouse eyes and the corresponding primary human UM. Unfortunately, the model is
not suitable for investigations of metastasis formation.
PMID- 27505447
TI - Fat Grafting for Neuropathic Pain After Severe Burns: Reply.
PMID- 27505448
TI - Myxofibrosarcoma in the Thenar Eminence.
AB - Myxofibrosarcoma is a rare cause of swelling in the upper extremities. The rarer
form arising in the deep tissues can present a diagnostic difficulty. The
treatment of high-grade myxofibrosarcoma in the extremity requires tissue
diagnosis, accurate staging, careful multidisciplinary agreement on treatment,
accurate execution of that treatment, and finally regular specialist
surveillance. The treatment must be planned on an individual basis, weighing the
risk of distant metastasis against the potential for severe functional impairment
should radical excision or amputation be performed. The grade of tumor, clinical
stage as well as the site, local extent, and the comorbidity of the patient
influence the decision.We present the case of an elderly woman with an expanding
high-grade myxofibrosarcoma within the thenar musculature of the nondominant
hand. She presented with early signs of complex regional pain syndrome, leading
to a treatment dilemma. We feel this case has important learning points on
assessing objectives, risks, and outcomes in the management of these types of
cases, and it highlights the role of multidisciplinary involvement in sarcoma
management.
PMID- 27505449
TI - The Impact of Diabetes Mellitus on Wound Healing in Breast Reconstruction.
AB - BACKGROUND: Although diabetes mellitus (DM) is a known risk factor for surgical
complications in general, there is little published evidence to establish such an
effect among patients undergoing breast reconstruction (BR). The purpose of this
study was to assess the impact of DM on complications in patients undergoing
postmastectomy BR. METHODS: Patients who underwent BR at our institution from
November 2002 to November 2012 were identified. Clinical and demographic data of
patients with type 1 or type 2 DM were reviewed. Complications occurring within
60 days of surgery were compared between diabetic and nondiabetic patients for
both autologous and nonautologous reconstruction types. RESULTS: A total of 1371
BR were performed in 1035 patients. There were 877 (64.0%) autologous
reconstructions and 494 (36.0%) implant-based reconstructions. Patients with DM
(n = 64) had significantly higher preoperative blood glucose levels (137.5 vs
100.1, P < 0.05). Postoperatively, DM patients reconstructed with implants had a
significantly higher incidence of delayed wound healing (22.2% vs 9.7%; P =
0.04). This was not observed in patients with DM reconstructed with autologous
tissue (7.4% vs 6.6%; P = 0.70). Diabetic patients had a significantly higher
incidence of hypertension and were older than nondiabetic patients. To control
for these variables and other potential confounders, multiple logistic regression
analysis was performed. Again, diabetic patients had a significantly higher
incidence of delayed wound healing following implant-based reconstruction (odds
ratio, 2.52, 95% confidence interval = 1.2-6.2) but not autologous reconstruction
(odds ratio, 0.97; 95% confidence interval = 0.2-4.6). CONCLUSIONS: Diabetes
heightens the risk of wound healing complications among patients undergoing
implant-based reconstruction.
PMID- 27505450
TI - Management of the Nipple-Areola Complex in Selected Patients Undergoing Primary
Breast Reconstruction: A Comparison of Immediate Replantation and Delayed
Reconstruction.
AB - BACKGROUND: Management of the nipple-areola complex is an important issue in
primary breast reconstruction. When nipple-sparing mastectomy is not suitable,
alternatives are immediate nipple-areola complex replantation and delayed
reconstruction. The aim of this study was to examine whether patients benefit
more from nipple-areola complex preservation by immediate replantation or delayed
nipple-areola complex reconstruction. METHODS: Postoperative results and patient
satisfaction after 54 primary breast reconstructions with immediate nipple-areola
complex replantation or delayed nipple-areola complex reconstruction were
retrospectively evaluated. RESULTS: The nipple-areola complex was replanted
immediately in 37 cases and reconstructed later with nipple sharing and full
thickness skin grafting in 17 cases. Compared with immediate replantation,
delayed reconstruction resulted in significantly better postoperative nipple
projection (P = 0.01*, Mann-Whitney U test), greater similarity of color and
projection with the contralateral side and greater patient satisfaction (Breast
Q). Complete loss of projection occurred in 4 of the 37 replanted nipple-areola
complexes. No complete nipple-areola complex necrosis or tumor recurrence was
observed in any patient. CONCLUSIONS: Immediate nipple-areola complex
replantation is a safe and reliable procedure for selected patients with
contraindications for nipple-sparing mastectomy who have a strong desire to
maintain their own nipple-areola complexes, or in bilateral cases. However,
drawbacks of this procedure include loss of projection and depigmentation.
Delayed reconstruction with nipple sharing and full-thickness skin grafting is a
good alternative, especially in unilateral cases; it leads to better
postoperative results and greater patient satisfaction, but it involves a nipple
areola complex-free period.
PMID- 27505451
TI - The new generation synthetic reconstituted surfactant CHF5633 suppresses LPS
induced cytokine responses in human neonatal monocytes.
AB - BACKGROUND: New generation synthetic surfactants represent a promising
alternative in the treatment of respiratory distress syndrome in preterm infants.
CHF5633, a new generation reconstituted agent, has demonstrated biophysical
effectiveness in vitro and in vivo. In accordance to several well-known
surfactant preparations, we recently demonstrated anti-inflammatory effects on
LPS-induced cytokine responses in human adult monocytes. The present study
addressed pro- and anti-inflammatory effects of CHF5633 in human cord blood
monocytes. METHODS: Purified neonatal CD14(+) cells, either native or
simultaneously stimulated with E. coli LPS, were exposed to CHF5633. TNF-alpha,
IL-1beta, IL-8 and IL-10 as well as TLR2 and TLR4 expression were analyzed by
means of real-time quantitative PCR and flow cytometry. RESULTS: CHF5633 did not
induce pro-inflammation in native human neonatal monocytes and did not aggravate
LPS-induced cytokine responses. Exposure to CHF5633 led to a significant decrease
in LPS-induced intracellular TNF-alpha protein expression, and significantly
suppressed LPS-induced mRNA and intracellular protein expression of IL-1beta.
CHF5633 incubation did not affect cell viability, indicating that the suppressive
activity was not due to toxic effects on neonatal monocytes. LPS-induced IL-8, IL
10, TLR2 and TLR4 expression were unaffected. CONCLUSION: Our data confirm that
CHF5633 does not exert unintended pro-apoptotic and pro-inflammatory effects in
human neonatal monocytes. CHF5633 rather suppressed LPS-induced TNF-alpha and IL
1beta cytokine responses. Our data add to previous work and may indicate anti
inflammatory features of CHF5633 on LPS-induced monocyte cytokine responses.
PMID- 27505452
TI - Frontal fibrosing alopecia in male patients: a report of 12 cases.
PMID- 27505453
TI - Clinician's Commentary on Keep et al.(1).
PMID- 27505454
TI - Beauty from the beast: Avoiding errors in responding to client questions.
AB - Those rare moments when clients ask direct questions of their therapists likely
represent a point when they are particularly open to new considerations, thereby
representing an opportunity for substantial therapeutic gains. However, clinical
errors abound in this area because clients' questions often engender apprehension
in therapists, causing therapists to respond with too little or too much
information or shutting down the discussion prematurely. These response types can
damage the therapeutic relationship, the psychotherapy process, or both. We
explore the nature of these clinical errors in response to client questions by
providing examples from our own clinical work, suggesting potential reasons why
clinicians may not make optimal use of client questions, and discussing how the
mixed psychological literature further complicates the issue. We also present
four guidelines designed to help therapists, trainers, and supervisors respond
constructively to clinical questions in order to create constructive
interactions. (PsycINFO Database Record
PMID- 27505455
TI - Clinical errors in cognitive-behavior therapy.
AB - Although cognitive-behavioral therapy (CBT) has been shown to be highly effective
for a wide range of disorders, many patients do not benefit. The failure to fully
benefit from CBT may be due to a wide range of factors, one of which includes
"clinical errors" that often occur during the therapeutic process. We briefly
note 4 such clinical errors including neglecting to conduct a detailed functional
analysis of the presenting problem(s), not adequately engaging the patient in
developing a case formulation for the purposes of treatment planning, getting
wrapped up in simply examining beliefs without behavioral tests, and not holding
patients accountable for fear of rupturing the therapeutic alliance. We then
discuss the context in which these clinical errors may occur during CBT and
highlight alternative approaches. Being mindful of these and other potential
clinical errors during CBT may facilitate better treatment outcomes. (PsycINFO
Database Record
PMID- 27505456
TI - Can we collaborate? Mistakes made when group and individual therapists ignore
multiple realities.
AB - Often, group therapists collaborate with individual therapists in conjoint
treatment. Many of these patients start in individual therapy and are referred to
the group to help facilitate the treatment and address interpersonal and
relational issues that either cannot or will not be addressed in the individual
work. Although this has the potential to foster incredible growth for patients,
it may also cause problems in treatment when collaboration between therapists
falls apart. The current paper will examine mistakes made when multiple realities
about a patient are ignored during the pregroup screening and preparation, and
feedback from group treatment is not integrated into individual therapy. Clinical
examples will be used with specific recommendations for combined treatment
planning and interventions. (PsycINFO Database Record
PMID- 27505457
TI - Clinical errors that can occur in the treatment decision-making process in
psychotherapy.
AB - Clinical errors occur in the psychotherapy decision-making process whenever a
less-than-optimal treatment or approach is chosen when working with clients. A
less-than-optimal approach may be one that a client is unwilling to try or fully
invest in based on his/her expectations and preferences, or one that may have
little chance of success based on contraindications and/or limited research
support. The doctor knows best and the independent choice models are two decision
making models that are frequently used within psychology, but both are associated
with an increased likelihood of errors in the treatment decision-making process.
In particular, these models fail to integrate all three components of the
definition of evidence-based practice in psychology (American Psychological
Association, 2006). In this article we describe both models and provide examples
of clinical errors that can occur in each. We then introduce the shared decision
making model as an alternative that is less prone to clinical errors.
PMID- 27505458
TI - Characterization of the Bread Made with Durum Wheat Semolina Rendered Gluten Free
by Sourdough Biotechnology in Comparison with Commercial Gluten-Free Products.
AB - Durum wheat semolina was fermented with sourdough lactic acid bacteria and fungal
proteases aiming at a complete gluten hydrolysis. The gluten-free (GF) semolina,
added with naturally GF ingredients and structuring agents, was used to produce
bread (rendered GF bread; rGFB) at industrial level. An integrated approach
including the characterization of the main chemical, nutritional, structural, and
sensory features was used to compare rGFB to a gluten-containing bread and to 5
commercial naturally GF breads. High-performance liquid chromatography was used
for free amino acids (FAAs), organic acids, and ethanol analysis. A methanolic
extract was used for determining total phenols and antioxidant activity. The
bread characterization also included the analysis of dietary fibers, mycotoxins,
vitamins, and heavy metals. Beyond chemical analysis, nutritional profile was
evaluated considering the in vitro protein digestibility and the predicted
glycemic index, while the instrumental texture profile analysis was performed to
investigate the structure and the physical/mechanical properties of the baked
goods. Beyond the huge potential of market expansion, the main advantages of
durum wheat semolina rendered GF can be resumed in the high availability of FAAs,
the high protein digestibility, the low starch hydrolysis index, and the better
technological properties of bread compared to the commercial GF products
currently present on the market. Vitamins, minerals, and dietary fiber profiles
are comparable to those of gluten-containing wheat bread. Also the sensory
profile, determined by a panel test, can be considered the most similar to those
of conventional baked goods, showing all the sourdough bread classic attributes.
PMID- 27505459
TI - cis-2,5-Diaminobicyclo[2.2.2]octane, a New Chiral Scaffold for Asymmetric
Catalysis.
AB - Catalysis of widely used chemical transformations in which the goal is to obtain
the product as a pure enantiomer has become a major preoccupation of synthetic
organic chemistry over the past three decades. A large number of chiral entities
has been deployed to this end, many with considerable success, but one of the
simplest and most effective catalytic systems to have emerged from this effort is
that based on a chiral diamine, specifically trans-1,2-diaminocyclohexane. While
there have been attempts to improve upon this scaffold in asymmetric synthesis,
few have gained the recognition needed to take their place alongside this classic
diamine. The challenge is to design a scaffold that retains the assets of trans
1,2-diaminocyclohexane while enhancing its intrinsic chirality and maximizing the
scope of its applications. It occurred to us that cis-2,5
diaminobicyclo[2.2.2]octane could be such a scaffold. Synthesis of this diamine
in enantiopure form was completed from benzoic acid, and the (1R,2R,4R,5R)
enantiomer was used in all subsequent experiments in this laboratory.
Condensation of the diamine with various salicyl aldehydes generated imine
derivatives which proved to be excellent "salen" ligands for encapsulation of
transition and other metals. In total, 12 salen-metal complexes were prepared
from this ligand, many of which were crystalline and three of which, along with
the ligand itself, yielded to X-ray crystallography. An advantage of this ligand
is that it can be tuned sterically or electronically to confer specific catalytic
properties on the salen-metal complex, and this feature was used in several
applications of our salen-metal complexes in asymmetric synthesis. Thus,
replacement of one of the tert-butyl groups in each benzenoid ring of the salen
ligand by a methoxy substituent enhanced the catalytic efficiency of a cobalt(II)
salen complex used in asymmetric cyclopropanation of 1,1-disubstituted alkenes;
the catalyst was employed in an improved synthesis of the cyclopropane-containing
drug candidate Synosutine. Reduction of the pair of imine functions of the ligand
to secondary amines permitted formation of a copper(I)-salen complex that
catalyzed asymmetric Henry ("nitroaldol") condensation with excellent efficiency;
this catalyst was applied in an economical synthesis of three drugs of the "beta
blocker" family including (S)-Propanolol. Chromium(II) and chromium(III)
complexes were prepared from our bicyclooctane-salen ligand bearing a pair of
tert-butyl groups in each benzenoid ring. These complexes were found to catalyze,
respectively, enantioselective formation of homoallylic alcohols from Nozaki
Hiyama-Kishi allylation of aromatic aldehydes and dihydropyranones from hetero
Diels-Alder cycloaddition. Plausible reaction models emerging from knowledge of
the absolute configuration of products from each of these reactions place the
metal-coordinated substrate in a quadrant beneath the bicyclooctane scaffold so
that one face of the substrate is blocked by an aryl ring of the salen ligand
while the opposite face is left open to attack. The consistent and predictable
stereochemical outcome from reactions catalyzed by salen-metal complexes derived
from our diaminobicyclo[2.2.2]octane scaffold adds a valuable new dimension to
asymmetric synthesis.
PMID- 27505460
TI - Erratum.
PMID- 27505463
TI - Instructions for Contributors.
PMID- 27505461
TI - Erratum.
PMID- 27505464
TI - Lipodystrophy, Diabetes and Normal Serum Insulin in PPARgamma-Deficient Neonatal
Mice.
AB - Peroxisome proliferator activated receptor gamma (PPARgamma) is a pleiotropic
ligand activated transcription factor that acts in several tissues to regulate
adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose
homeostasis. PPARgamma also regulates cardiomyocyte homeostasis and by virtue of
its obligate role in placental development is required for embryonic survival. To
determine the postnatal functions of PPARgamma in vivo we studied globally
deficient neonatal mice produced by epiblast-restricted elimination of PPARgamma.
PPARgamma-rescued placentas support development of PPARgamma-deficient embryos
that are viable and born in near normal numbers. However, PPARgamma-deficient
neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal
hepatitis, relative insulin deficiency and diabetes beginning soon after birth
and culminating in failure to thrive and neonatal lethality between 4 and 10 days
of age. These abnormalities are not observed with selective PPARgamma2 deficiency
or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes,
cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest
important but previously unappreciated functions for PPARgamma1 in the neonatal
period either alone or in combination with PPARgamma2 in lipid metabolism,
glucose homeostasis and insulin sensitivity.
PMID- 27505465
TI - Homoleptic Poly(nitrato) Complexes of Group 14 Stable at Ambient Conditions.
AB - Using a novel approach in homoleptic nitrate chemistry, Sn(NO3)6(2-) (3c) as well
as the previously unknown hexanitrato complexes Si(NO3)6(2-) (1c), Ge(NO3)6(2-)
(2c) were synthesized from the element tetranitrates as salt-like compounds which
were isolated and characterized using (1)H, (14)N, and (29)Si NMR and IR
spectroscopies, elemental and thermal analyses, and single-crystal XRD. All
hexanitrates are moderately air-sensitive at 298 K and possess greater thermal
stability toward NO2 elimination than their charge-neutral tetranitrato congeners
as solids and in solution. The complexes possess distorted octahedral
coordination skeletons and adopt geometries that are highly symmetric (3c) or
deformed (1c, 2c) depending on the degree of steric congestion of the ligand
sphere. As opposed to the kappa(2)O,O' coordination mode reported for Sn(NO3)4
previously,1 all nitrato ligands of 3c coordinate in kappa(1)O mode. Six
geometric isomers of E(NO3)6(2-) were identified as minima on the PES using DFT
calculations at the B3LYP/6-311+G(d,p) level of which two were observed
experimentally.
PMID- 27505466
TI - Moral typecasting underlies punitive responses to crime.
AB - We examine the role of moral typecasting in lay individuals' punitive responses
to crime. Individuals perceive criminal offenders and victims in ways that are
biased by their perceptions of the actors' moral roles in prior simulated
criminal incidents. We find that this psychological process of moral typecasting
has important implications for punitive responses to criminal offenders, and
these findings make 2 major contributions to the literature. First, we show that
moral agency is distinct from moral deservingness, which is 1 of the dominant
explanations for punitive behavior in social psychology. Second, the role of
moral typecasting in punitive responses means that these responses can occur
regardless of the valence of moral character. We argue that theories of lay
punitive responding that do not take moral typecasting processes into account are
incomplete. (PsycINFO Database Record
PMID- 27505467
TI - Health Care Use Outcomes of an Integrated Hospital-to-Home Mother-Preterm Infant
Intervention.
AB - OBJECTIVE: To compare health care use from initial hospital discharge through 6
weeks corrected age in two groups of mother-preterm infant dyads: those who
received an intervention, Hospital to Home: Optimizing Premature Infant's
Environment (H-HOPE), and an attention control group. DESIGN: Prospective
randomized controlled trial. SETTING: Two community hospital NICUs. PARTICIPANTS:
Mothers (n = 147) with social-environmental risk factors and their stable preterm
infants. METHODS: Mother-infant dyads were randomly assigned to the H-HOPE or
control group. When infants reached 6 weeks corrected age, information about
health care visits since their hospital discharges was collected through an
interview. RESULTS: Only half of all infants received all recommended well-child
visits. Infants in H-HOPE were half as likely to have acute care episodes
(illness visit to the clinic or emergency department or hospital readmission) as
control infants (odds ratio [OR] = 0.46, 95% confidence interval [CI] [0.22,
0.95]). Infants of mothers with high trait anxiety were nearly 3 times more
likely to have an acute care episode (OR = 2.78, 95% CI [1.05, 7.26]), and
mothers who had low education levels (OR = .22, 95% CI [0.08, 0.60]) were less
likely to have acute care episodes. There was a trend toward fewer acute care
visits for infants whose mothers preferred an English interview (OR = .47, 95% CI
[0.21, 1.06]). CONCLUSION: Findings emphasize the importance of reinforcing well
child visits for vulnerable preterm infants. H-HOPE, an integrated mother-infant
intervention, reduces acute care episodes (visits to the clinic or emergency
department or hospital readmissions) for preterm infants.
PMID- 27505606
TI - Liberating the kidney from continuous renal replacement therapy.
PMID- 27505605
TI - The rocking method of artificial respiration.
PMID- 27505607
TI - Procedural pain in intensive care: translating awareness into practice.
PMID- 27505608
TI - Images of Australians and Anaesthesia from World War 1.
PMID- 27505611
TI - The Effect of Ginger on Breast Milk Volume in the Early Postpartum Period: A
Randomized, Double-Blind Controlled Trial.
AB - BACKGROUND: In Thailand, ginger is a popular natural galactagogue among
breastfeeding women. However, there has never been evidence to support the
effectiveness of ginger in increasing the breast milk volume. OBJECTIVES: To
compare breast milk volume on the third and seventh day postpartum between
lactating mothers who receive 500 mg dried ginger capsules twice daily with those
receiving placebo. MATERIALS AND METHODS: A randomized, double-blind controlled
trial was conducted. Women who deliver a term baby were randomly assigned to
receive dried ginger or placebo for 7 days postpartum. Breast milk volume was
measured on third day postpartum using test weight method for a period of 24
hours and on seventh day postpartum using 1 hour milk production. We also
compared the third day serum prolactin level between the two groups. RESULTS:
Data from 63 women were available for analysis, 30 from the ginger group and 33
from the placebo group. The two groups were similar regarding baseline
characteristics. Women in the ginger group have higher milk volume than the
placebo group (191.0 +/- 71.2 mL/day versus 135.0 +/- 61.5 mL/day, p < 0.01).
However, the seventh day milk volume in the ginger group does not differ from the
placebo group (80.0 +/- 58.5 mL versus 112.1 +/- 91.6 mL, p = 0.24). The mean
serum prolactin levels were similar in both groups (321.5 +/- 131.8 ng/L in the
ginger group, and 331.4 +/- 100.7 ng/L in the placebo group, p = 0.74). No side
effect was reported in this study. CONCLUSION: Ginger is a promising natural
galactagogue to improve breast milk volume in the immediate postpartum period
without any notable side effect.
PMID- 27505612
TI - Ultrasound-Guided Placement of Gold Fiducial Markers for Stereotactic Partial
Breast Irradiation.
AB - OBJECTIVE: A novel technique of placing gold fiducial markers in the breast using
ultrasound guidance was developed and performed in 51 of 55 consecutive
postlumpectomy patients enrolled in a phase I dose escalation trial of
accelerated partial-breast irradiation (APBI) using robotic-based stereotactic
body radiation therapy (SBRT). CONCLUSION: All 51 postoperative patients
underwent successful fiducial placement without complications. Our technique of
placing gold fiducial markers in proximity to the seroma cavity is considered
safe and effective for breast cancer patients being treated with APBI using
robotic-based SBRT.
PMID- 27505613
TI - Imaging nanoscale lattice variations by machine learning of x-ray diffraction
microscopy data.
AB - We present a novel methodology based on machine learning to extract lattice
variations in crystalline materials, at the nanoscale, from an x-ray Bragg
diffraction-based imaging technique. By employing a full-field microscopy setup,
we capture real space images of materials, with imaging contrast determined
solely by the x-ray diffracted signal. The data sets that emanate from this
imaging technique are a hybrid of real space information (image spatial support)
and reciprocal lattice space information (image contrast), and are intrinsically
multidimensional (5D). By a judicious application of established unsupervised
machine learning techniques and multivariate analysis to this multidimensional
data cube, we show how to extract features that can be ascribed physical
interpretations in terms of common structural distortions, such as lattice tilts
and dislocation arrays. We demonstrate this 'big data' approach to x-ray
diffraction microscopy by identifying structural defects present in an epitaxial
ferroelectric thin-film of lead zirconate titanate.
PMID- 27505614
TI - Heterocyclic Bismuth(III) Dithiocarbamato Complexes as Single-Source Precursors
for the Synthesis of Anisotropic Bi2 S3 Nanoparticles.
AB - New complexes catena-(MU2 -nitrato
O,O')bis(piperidinedithiocarbamato)bismuth(III) (1) and tetrakis(MU
nitrato)tetrakis[bis(tetrahydroquinolinedithiocarbamato)bismuth(III)] (2) were
synthesised and characterised by elemental analysis, FTIR spectroscopy and
thermogravimetric analysis. The single-crystal X-ray structures of 1 and 2 were
determined. The coordination numbers of the Bi(III) ion are 8 for 1 and >=6 for 2
when the experimental electron density for the nominal 6s(2) lone pair of
electrons is included. Both complexes were used as single-source precursors for
the synthesis of dodecylamine-, hexadecylamine-, oleylamine and tri-n
octylphosphine oxide-capped Bi2 S3 nanoparticles at different temperatures.
UV/Vis spectra showed a blueshift in the absorbance band edge characteristic of a
quantum size effect. High-quality, crystalline, long and short Bi2 S3 nanorods
were obtained depending on the thermolysis temperature, which was varied from 190
to 270 degrees C. A general trend of increasing particle breadth with increasing
reaction temperature and increasing length of the carbon chain of the amine
(capping agent) was observed. Powder XRD patterns revealed the orthorhombic
crystal structure of Bi2 S3 .
PMID- 27505615
TI - Application of Chemical Force Microscopy for Finding Selective Functional Groups
for Discriminating Different Electronic Type Single-Walled Carbon Nanotubes.
PMID- 27505616
TI - MSL1 is a mechanosensitive ion channel that dissipates mitochondrial membrane
potential and maintains redox homeostasis in mitochondria during abiotic stress.
AB - Mitochondria must maintain tight control over the electrochemical gradient across
their inner membrane to allow ATP synthesis while maintaining a redox-balanced
electron transport chain and avoiding excessive reactive oxygen species
production. However, there is a scarcity of knowledge about the ion transporters
in the inner mitochondrial membrane that contribute to control of membrane
potential. We show that loss of MSL1, a member of a family of mechanosensitive
ion channels related to the bacterial channel MscS, leads to increased membrane
potential of Arabidopsis mitochondria under specific bioenergetic states. We
demonstrate that MSL1 localises to the inner mitochondrial membrane. When
expressed in Escherichia coli, MSL1 forms a stretch-activated ion channel with a
slight preference for anions and provides protection against hypo-osmotic shock.
In contrast, loss of MSL1 in Arabidopsis did not prevent swelling of isolated
mitochondria in hypo-osmotic conditions. Instead, our data suggest that ion
transport by MSL1 leads to dissipation of mitochondrial membrane potential when
it becomes too high. The importance of MSL1 function was demonstrated by the
observation of a higher oxidation state of the mitochondrial glutathione pool in
msl1-1 mutants under moderate heat- and heavy-metal-stress. Furthermore, we show
that MSL1 function is not directly implicated in mitochondrial membrane potential
pulsing, but is complementary and appears to be important under similar
conditions.
PMID- 27505617
TI - Super Aryl-Extended Calix[4]pyrroles: Synthesis, Binding Studies, and Attempts To
Gain Water Solubility.
AB - We describe the synthesis of unprecedented calix[4]pyrrole receptors featuring
"super aryl extended" (SAE) cavities. We elaborated the aromatic cavity provided
by the alphaalphaalphaalpha-isomer of para-tetraiodo-meso-phenyl calix[4]pyrrole
by installing ethynyl-aryl substituents at its upper rim. We report the binding
properties of the prepared SAE-calix[4]pyrrole tetraester towards pyridyl-N
oxides. The binding data revealed the formation of thermodynamically and
kinetically highly stable 1:1 complexes. The complexation-induced chemical shifts
indicated the formation of hydrogen bonds and aromatic interactions with the
calix-core adopting the cone conformation. We quantified the additional
interactions established between the four terminal aryl groups and the para
phenyl substituent of 4-phenyl pyridine N-oxide to be in the order of 1 kcal mol(
1) . The complex formation rate was found to be close to the diffusion control
suggesting that the free host adopted a 1,3-alternate conformation. Finally, we
attempted to gain water solubility of SAE-calix[4]pyrroles using derivatives that
display four ionizable or charged groups at their upper rims.
PMID- 27505619
TI - Imaging review of hepatocellular carcinoma after thermal ablation: The good, the
bad, and the ugly.
AB - Image-guided thermal ablation is a well-established locoregional technique for
the treatment of hepatocellular carcinoma (HCC). HCC surveillance programs have
led to an increase in the number of patients diagnosed at an early stage of the
disease who are eligible for thermal ablation. Tumor response is assessed on
imaging and requires extensive follow-up; thus, radiologists play a key role in
defining the technical success and efficacy of treatment as well as identifying
progressive disease. Although they are rare, complications, such as secondary
infections, must also be identified. Several contrast-enhanced imaging techniques
can be used at different postprocedural timepoints but magnetic resonance imaging
(MRI) and computed tomography (CT), which allow both liver-centered and whole
body imaging are the cornerstones of follow-up. This review describes the imaging
features of HCC following thermal ablation. After describing the basic technical
elements of follow-up imaging, imaging findings are divided into three groups:
normal and expected features (the good), abnormal features, uncontrolled disease,
and complications (the bad), and atypical or rare presentations (the ugly). J.
Magn. Reson. Imaging 2016;44:1070-1090.
PMID- 27505620
TI - Using Guest-Host Interactions To Optimize the Efficiency of TADF OLEDs.
AB - We show that the emitter and host combination must be optimized to minimize the
reverse intersystem crossing (rISC) barrier and maximize thermally activated
delayed fluorescence (TADF). The blue TADF emitter, 2,7-bis(9,9-dimethyl-acridin
10-yl)-9,9-dimethylthioxanthene-S,S-dioxide (DDMA-TXO2), has strong TADF
character due to efficient charge transfer (CT) state formation. By combining
DDMA-TXO2 with a host of correct polarity (DPEPO) that relaxes the CT manifolds'
energy to become resonant with the lowest-energy local triplet state of DDMA
TXO2, the emitter and host combination produce a minimum rISC barrier (DeltaEST),
which maximizes TADF efficiency. We show that the sensitivity of these splittings
is highly dependent on emitter environment and must be carefully tuned to
optimize device performance. Devices utilizing DDMA-TXO2 in the DPEPO host show
blue electroluminescence (EL), with commission internationale de l'eclairage
(CIE) chromaticity coordinates of CIE (0.16, 0.24), with a maximum external
quantum efficiency of 22.4%. This high device performance is a direct consequence
of optimizing the TADF efficiency by this "host tuning".
PMID- 27505621
TI - Combination of a peptide-modified gellan gum hydrogel with cell therapy in a
lumbar spinal cord injury animal model.
AB - Spinal Cord Injury (SCI) is a highly incapacitating condition for which there is
still no cure. Current clinical approaches are mainly based on palliative care,
so there is a need to find possible treatments to SCI. Cellular transplantation
is regarded with great expectation due to the therapeutic potential of cells such
as Adipose tissue-derived Stromal/Stem Cells (ASCs) or Olfactory Ensheathing
Cells (OECs). Both are accessible sources and present positive paracrine and cell
to-cell interactions, previously reported by our group. Additionally,
biomaterials such as hydrogels have been applied in SCI repair with promising
results. We propose to combine a GRGDS-modified gellan gum hydrogel with ASCs and
OECs in order to promote SCI regeneration. In vitro, ASCs and OECs could be co
cultured within GG-GRGDS hydrogels inducing a more robust neurite outgrowth when
compared to controls. In vivo experiments in a hemisection SCI rat model revealed
that the administration of ASCs and OECs encapsulated in a GG-GRGDS hydrogel led
to significant motor improvements when compared to both control (SCI) and
hydrogel alone (GG-GRGDS) groups. This was accompanied by a decreased
infiltration of inflammatory cells and astrocytes, and by an increased intensity
of neurofilament. These results suggest evident gains induced by the
encapsulation of ASCs and OECs in GG-GRGDS based hydrogels.
PMID- 27505622
TI - Identifying highly influential nodes in the complicated grief network.
AB - The network approach to psychopathology conceptualizes mental disorders as
networks of mutually reinforcing nodes (i.e., symptoms). Researchers adopting
this approach have suggested that network topology can be used to identify
influential nodes, with nodes central to the network having the greatest
influence on the development and maintenance of the disorder. However, because
commonly used centrality indices do not distinguish between positive and negative
edges, they may not adequately assess the nature and strength of a node's
influence within the network. To address this limitation, we developed 2 indices
of a node's expected influence (EI) that account for the presence of negative
edges. To evaluate centrality and EI indices, we simulated single-node
interventions on randomly generated networks. In networks with exclusively
positive edges, centrality and EI were both strongly associated with observed
node influence. In networks with negative edges, EI was more strongly associated
with observed influence than was centrality. We then used data from a
longitudinal study of bereavement to examine the association between (a) a node's
centrality and EI in the complicated grief (CG) network and (b) the strength of
association between change in that node and change in the remainder of the CG
network from 6- to 18-months postloss. Centrality and EI were both correlated
with the strength of the association between node change and network change.
Together, these findings suggest high-EI nodes, such as emotional pain and
feelings of emptiness, may be especially important to the etiology and treatment
of CG. (PsycINFO Database Record
PMID- 27505623
TI - Trends in diabetes and obesity in Samoa over 35 years, 1978-2013.
AB - AIMS: Population surveys of Type 2 diabetes mellitus and obesity conducted in
Samoa over three decades have used varying methodologies and definitions. This
study standardizes measures, and trends of Type 2 diabetes mellitus and obesity
for 1978-2013 are projected to 2020 for adults aged 25-64 years. METHODS: Unit
records from eight surveys (n = 12 516) were adjusted to the previous census for
Division of residence, sex and age to improve national representativeness. Type 2
diabetes mellitus is defined as a fasting plasma glucose >= 7.0 mmol/l and/or on
medication. Obesity is defined as BMI >= 30 kg/m2 . Random effects meta
regression was employed to assess time trends following logit transformation.
Poisson regression from strata was used to assess the effects of mean BMI changes
on Type 2 diabetes mellitus period trends. RESULTS: Over 1978-2013, Type 2
diabetes mellitus prevalence increased from 1.2% to 19.6% in men (2.3% per 5
years), and from 2.2% to 19.5% in women (2.2% per 5 years). Obesity prevalence
increased from 27.7% to 53.1% in men (3.6% per 5 years) and from 44.4% to 76.7%
(4.5% per 5 years) in women. Type 2 diabetes mellitus and obesity prevalences
increased in all age groups. From period trends, Type 2 diabetes mellitus
prevalence in 2020 is projected to be 26% in men and women. Projected obesity
prevalence is projected to be 59% in men and 81% in women. Type 2 diabetes
mellitus period trends attributable to BMI increase are estimated as 31% (men)
and 16% (women), after adjusting for age. CONCLUSION: This is the first study to
produce trends of Type 2 diabetes mellitus and obesity in Samoa based on
standardized data from population surveys. Type 2 diabetes mellitus is equally
prevalent in both sexes, and obesity is widespread. Type 2 diabetes mellitus
prevalence in Samoa is likely to continue to increase in the near future.
PMID- 27505624
TI - Vision Therapy for Post-Concussion Vision Disorders.
AB - PURPOSE: To determine the frequency and types of vision disorders associated with
concussion, and to determine the success rate of vision therapy for these
conditions in two private practice settings. METHODS: All records over an 18
month period of patients referred for post-concussion vision problems were
reviewed from two private practices. Diagnoses of vergence, accommodative, or eye
movement disorders were based on pre-established, clinical criteria. Vision
therapy was recommended based on clinical findings and symptoms. RESULTS: Two
hundred eighteen patient records were found with a diagnosis of concussion. Fifty
six percent of the concussions were related to sports, 20% to automobile
accidents, and 24% to school, work, or home-related incidents. The mean age was
20.5 years and 58% were female. Eighty-two percent of the patients had a
diagnosis of an oculomotor problem [binocular problems (62%), accommodative
problems (54%), eye movement problems (21%)]. The most prevalent diagnoses were
convergence insufficiency (CI, 47%) and accommodative insufficiency (AI, 42%).
Vision therapy was recommended for 80% of the patients. Forty-six per cent
(80/175) either did not pursue treatment or did not complete treatment. Of the
54% (95/175) who completed therapy, 85% of patients with CI were successful and
15% were improved, and with AI, 33% were successful and 67% improved. Clinically
and statistically significant changes were measured in symptoms, near point of
convergence, positive fusional vergence, and accommodative amplitude.
CONCLUSIONS: In this case series, post-concussion vision problems were prevalent
and CI and AI were the most common diagnoses. Vision therapy had a successful or
improved outcome in the vast majority of cases that completed treatment.
Evaluation of patients with a history of concussion should include testing of
vergence, accommodative, and eye movement function. Prospective clinical trials
are necessary to assess the natural history of concussion-related vision
disorders and treatment effectiveness.
PMID- 27505625
TI - Association of monocyte chemoattractant protein-1 gene 2518A/G polymorphism with
diabetic retinopathy in type 2 diabetes mellitus: A meta-analysis.
AB - AIMS: The relationship between monocyte chemoattractant protein-1 (MCP-1) 2518
A/G polymorphism and diabetic retinopathy (DR) attracted intense interest
recently, but the reported results are controversial. A meta-analysis was
performed to assess the MCP-1 polymorphism associated with DR susceptibility in
type 2 diabetes mellitus. METHODS: Eligible studies were identified from PubMed,
Embase, Web of science, Chinese Biomedical database, and references of retrieved
articles. Pooled odds ratios (ORs) with their 95% confidence intervals (95%CI)
were calculated by fixed or random-effects models. RESULTS: Six studies involving
3415 patients without DR and 3468 with any DR were included in the final meta
analysis. Each 5 studies evaluated the associations of MCP-1 polymorphism and any
DR and proliferative DR (PDR), respectively. Meta-analysis in fixed model
demonstrated a significant association between MCP-1 polymorphism and any DR
under the homozygous model (OR=1.36; 95%CI: 1.15-1.62, P<0.001), heterozygous
model (OR=1.20; 95%CI: 1.02-1.42, P=0.031), dominant model (OR=1.28; 95%CI: 1.10
1.50, P=0.002), recessive model (OR=1.17; 95%CI: 1.05-1.31, P=0.004), and allelic
model (OR=1.16; 95%CI: 1.07-1.25, P<0.001). Furthermore, a significant
association of MCP-1 polymorphism and DR progression from non-proliferative DR to
proliferative DR was identified under heterozygous model (OR=1.45; 95%CI: 1.04
2.02, P=0.030). Sensitivity analyses did not draw different findings.
CONCLUSIONS: Meta-analysis of existing data suggested that MCP-1 2518 A/G
polymorphism affected the risk of presence and progression of DR in type 2
diabetes mellitus.
PMID- 27505626
TI - Comparative Transcriptome Profiling of Human Foreskin Fibroblasts Infected with
the Sylvio and Y Strains of Trypanosoma cruzi.
AB - Trypanosoma cruzi, the causative agent of Chagas Disease, is phylogeneticaly
distributed into nearly identical genetic strains which show divergent clinical
presentations including differences in rates of cardiomyopathy in humans,
different vector species and transmission cycles, differential congenital
transmission in a mouse model, and differing immune and heart inflammation
response in dogs. The population structure of these strains divides into two
groups, which are geographically and clinically distinct. The aim of this study
was to compare the transcriptome of two strains of T. cruzi, Sylvio vs. Y, to
identify differences in expression that could account for clinical and
biochemical differences. We collected and sequenced RNA from T. cruzi-infected
and control Human Foreskin Fibroblasts at three timepoints. Differential
expression analysis identified gene expression different timepoints in Sylvio
infections, and between Sylvio and Y infections in both parasite and host. The
Sylvio strain parasite and the host response to Sylvio infection largely mirrored
the host-pathogen interaction seen in our previous Y strain work. IL-8 was more
highly expressed in Sylvio-infected HFFs than in Y-infected HFFs.
PMID- 27505628
TI - Evaluation of smokers with and without asthma in terms of smoking cessation
outcome, nicotine withdrawal symptoms, and craving: Findings from a self-guided
quit attempt.
AB - INTRODUCTION: The aim of the current study was to evaluate smoking cessation
outcome, nicotine withdrawal symptoms, and craving between smokers with (n=47;
46.8% male, Mage=40.0years, SD=11.7) and without (n=45; 51.1% male,
Mage=37.5years, SD=11.1) asthma during a self-guided quit attempt. METHODS: After
completing a baseline assessment visit, participants attended study sessions on
their scheduled quit day as well as follow-up visits (3days, 7days, 14days, and
28days) after their quit day. RESULTS: Smokers with and without asthma did not
differ in abstinence rates, smoking lapse, and rate of change in urge to smoke to
reduce negative affect. However, smokers with asthma demonstrated a slower rate
of decline in nicotine withdrawal symptoms and craving over time. CONCLUSIONS:
These findings suggest that smokers with asthma may benefit from specialized
smoking cessation treatments to address prolonged withdrawal symptoms and
craving.
PMID- 27505629
TI - Long-term oncological safety of minimally invasive surgery in high-risk
endometrial cancer.
AB - BACKGROUND: Several studies showed that women with low-risk endometrial cancers
staged by minimally invasive surgery (MIS) experience fewer postoperative
complications compared to those staged by laparotomy with similar disease-free
survival (DFS) and overall survival (OS). However, high-risk patients were poorly
represented. In this study, we compared DFS and OS in high-risk endometrial
cancer patients who underwent surgical staging via MIS versus laparotomy.
METHODS: Using a multicentric database, we compared DFS and OS between 114
patients with high-risk histology who underwent surgical staging via MIS and 114
patients who underwent laparotomy. Patients were matched for age, tumour type,
FIGO stage and management criteria. RESULTS: Among the 114 patients who underwent
MIS, 93 underwent laparoscopy and 21 robotic surgery. Groups were comparable for
stage, body mass index, histology and adjuvant therapies. However, patients in
the MIS group underwent paraaortic lymphadenectomy less frequently (13% versus
29%; p = 0.01), had less lymph nodes removed (19.0 versus 28.6; p < 0.01) and had
lower mean tumour size (30 versus 40 mm; p < 0.01). With a median follow-up time
of 49 months, DFS and OS were not significantly different between the surgical
cohorts. In multivariable analysis, both higher stage (hazard ratio [HR] = 2.2)
and histology (HR = 4.9) were associated with DFS in contrast to surgical
procedure (HR = 0.9). CONCLUSIONS: Beyond the benefit of MIS on immediate
surgical outcome, our results show that fear for a poor long-term outcome should
not be the reason to refrain from MIS in patients with high-risk endometrial
cancer.
PMID- 27505630
TI - New Look, New Features: An Update From the Journal of Clinical Neurophysiology.
PMID- 27505631
TI - Pierre J. Meunier.
PMID- 27505632
TI - Aerobic photoreactivity of synthetic eumelanins and pheomelanins: generation of
singlet oxygen and superoxide anion.
AB - In this work, we examined photoreactivity of synthetic eumelanins, formed by
autooxidation of DOPA, or enzymatic oxidation of 5,6-dihydroxyindole-2-carboxylic
acid and synthetic pheomelanins obtained by enzymatic oxidation of 5-S
cysteinyldopa or 1:1 mixture of DOPA and cysteine. Electron paramagnetic
resonance oximetry and spin trapping were used to measure oxygen consumption and
formation of superoxide anion induced by irradiation of melanin with blue light,
and time-resolved near-infrared luminescence was employed to determine the
photoformation of singlet oxygen between 300 and 600 nm. Both superoxide anion
and singlet oxygen were photogenerated by the synthetic melanins albeit with
different efficiency. At 450-nm, quantum yield of singlet oxygen was very low
(~10-4 ) but it strongly increased in the UV region. The melanins quenched
singlet oxygen efficiently, indicating that photogeneration and quenching of
singlet oxygen may play an important role in aerobic photochemistry of melanin
pigments and could contribute to their photodegradation and photoaging.
PMID- 27505633
TI - Clinical Features and Treatment Outcomes of Patients with Drug-Resistant and Drug
Sensitive Tuberculosis: A Historical Cohort Study in Porto Alegre, Brazil.
AB - PURPOSE: To evaluate the clinical features and treatment outcomes of patients
with pulmonary tuberculosis, stratified by level of drug resistance. METHODS:
This was a historical cohort study based on data from the II National Anti
Tuberculosis Drug Resistance Survey (2006-2007) collected at eight participating
health care facilities in Porto Alegre, southern Brazil. The cohort was followed
for 3 years after the start of treatment. RESULTS: Of 299 cases of smear-positive
pulmonary tuberculosis included in the study, 216 (72.2%) were diagnosed at five
public primary health care units and 83 (27.8%) at three public hospitals. Among
these cases, the prevalence of drug-resistant tuberculosis was 14.4%, and that of
multidrug-resistant tuberculosis was 4.7%. Overall, 32.0% of drug-resistant and
2.0% of multidrug-resistant cases occurred in previously treated patients. The
most common comorbidity in the sample was HIV infection (26.2%). There was no
association between drug-resistant or multidrug-resistant tuberculosis and
sociodemographic variables. Cure was achieved in 66.7% of patients, and the
default rate was 21.2%. The 2-month sputum conversion rate was 34.2%, and the
relapse rate was 16.9%. Patients with drug-resistant tuberculosis had lower rates
of cure (45.2%) and 2-month sputum conversion (25%), as well as a higher relapse
rate (30.7%). CONCLUSION: These results highlight the urgent need for a more
effective TB control program in this geographical setting, with a major emphasis
on treatment of drug-resistant and multidrug-resistant tuberculosis.
PMID- 27505634
TI - Sensitivity Analysis and Optimal Control of Anthroponotic Cutaneous Leishmania.
AB - This paper is focused on the transmission dynamics and optimal control of
Anthroponotic Cutaneous Leishmania. The threshold condition R0 for initial
transmission of infection is obtained by next generation method. Biological sense
of the threshold condition is investigated and discussed in detail. The
sensitivity analysis of the reproduction number is presented and the most
sensitive parameters are high lighted. On the basis of sensitivity analysis, some
control strategies are introduced in the model. These strategies positively
reduce the effect of the parameters with high sensitivity indices, on the initial
transmission. Finally, an optimal control strategy is presented by taking into
account the cost associated with control strategies. It is also shown that an
optimal control exists for the proposed control problem. The goal of optimal
control problem is to minimize, the cost associated with control strategies and
the chances of infectious humans, exposed humans and vector population to become
infected. Numerical simulations are carried out with the help of Runge-Kutta
fourth order procedure.
PMID- 27505635
TI - DWI in Pediatric Small-Bowel Crohn Disease: Are Apparent Diffusion Coefficients
Surrogates for Disease Activity in Patients Receiving Infliximab Therapy?
AB - OBJECTIVE: The purpose of this study was to determine prospectively whether bowel
wall apparent diffusion coefficient (ADC) measurements can be used to monitor
treatment response to infliximab therapy in the setting of pediatric small-bowel
Crohn disease. SUBJECTS AND METHODS: Twenty-eight pediatric subjects with newly
diagnosed biopsy-proven Crohn disease of the distal or terminal ileum treated
with infliximab were enrolled. Subjects underwent MR enterography at baseline, 1
month after therapy, and 6 months after therapy. Imaging features were
documented, including bowel wall ADC and arterial or enteric phase contrast
enhanced signal intensity normalized to that of unenhanced imaging. A linear
mixed model assessed the relationship between ADC and time; patient age and sex
and azathioprine combination therapy were covariates. The diagnostic performance
(with 95% CIs) of an increase in bowel wall ADC of 20% or more for identifying
response to infliximab was calculated using a decrease in normalized contrast
enhanced bowel wall signal intensity of 20% or more as the reference standard.
RESULTS: Bowel wall ADC increased over time (mean [+/- SD], 1180 +/- 200 * 10-6
mm2/s at baseline, 1420 +/- 420 * 10-6 mm2/s at 1 month, and 1450 +/- 450 * 10-6
mm2/s at 6 months; p = 0.0003); azathioprine therapy modulated this rate of
change (p = 0.003). There was a statistically significant negative correlation
between change in ADC and change in normalized contrast-enhanced signal intensity
over time (rho = -0.36; p < 0.001). The diagnostic performance of change in ADC
for identifying response to infliximab therapy was sensitivity of 0.58 (95% CI,
0.34-0.80), specificity of 0.52 (95% CI, 0.31-0.72), positive predictive value of
0.48 (95% CI, 0.27-0.69), and negative predictive value of 0.62 (95% CI, 0.38
0.82). CONCLUSION: Bowel wall ADC increases over time in pediatric subjects
receiving infliximab, but the diagnostic performance of ADC is likely
insufficient for reliable treatment monitoring.
PMID- 27505636
TI - Resolving and Tuning Mechanical Anisotropy in Black Phosphorus via Nanomechanical
Multimode Resonance Spectromicroscopy.
AB - Black phosphorus (P) has emerged as a layered semiconductor with a unique crystal
structure featuring corrugated atomic layers and strong in-plane anisotropy in
its physical properties. Here, we demonstrate that the crystal orientation and
mechanical anisotropy in free-standing black P thin layers can be precisely
determined by spatially resolved multimode nanomechanical resonances. This offers
a new means for resolving important crystal orientation and anisotropy in black P
device platforms in situ beyond conventional optical and electrical calibration
techniques. Furthermore, we show that electrostatic-gating-induced straining can
continuously tune the mechanical anisotropic effects on multimode resonances in
black P electromechanical devices. Combined with finite element modeling (FEM),
we also determine the Young's moduli of multilayer black P to be 116.1 and 46.5
GPa in the zigzag and armchair directions, respectively.
PMID- 27505637
TI - Impact of dose intensity of ponatinib on selected adverse events: Multivariate
analyses from a pooled population of clinical trial patients.
AB - Ponatinib is approved for adults with refractory chronic myeloid leukemia or
Philadelphia chromosome-positive acute lymphoblastic leukemia, including those
with the T315I BCR-ABL1 mutation. We pooled data from 3 clinical trials (N=671)
to determine the impact of ponatinib dose intensity on the following adverse
events: arterial occlusive events (cardiovascular, cerebrovascular, and
peripheral vascular events), venous thromboembolic events, cardiac failure,
thrombocytopenia, neutropenia, hypertension, pancreatitis, increased lipase,
increased alanine aminotransferase, increased aspartate aminotransferase, rash,
arthralgia, and hypertriglyceridemia. Multivariate analyses allowed adjustment
for covariates potentially related to changes in dosing or an event. Logistic
regression analysis identified significant associations between dose intensity
and most events after adjusting for covariates. Pancreatitis, rash, and cardiac
failure had the strongest associations with dose intensity (odds ratios >2). Time
to-event analyses showed significant associations between dose intensity and risk
of arterial occlusive events and each subcategory. Further, these analyses
suggested that a lag exists between a change in dose and the resulting change in
event risk. No significant association between dose intensity and risk of venous
thromboembolic events was evident. Collectively, these findings suggest a
potential causal relationship between ponatinib dose and certain adverse events
and support prospective investigations of approaches to lower average ponatinib
dose intensity.
PMID- 27505638
TI - A Novel Plasmid, pSx1, Harboring a New Tn1696 Derivative from Extensively Drug
Resistant Shewanella xiamenensis Encoding OXA-416.
AB - The whole genome sequencing of extensively drug-resistant Shewanella xiamenensis
T17 isolated from hospital effluents in Algeria revealed the presence of a novel
268.4 kb plasmid designated pSx1, which carries several antibiotic-resistance
genes in the novel Tn1696 derivative (Tn6297), in addition to the chromosomal
blaOXA-48-like gene (blaOXA-416). The presence of the plasmid was confirmed by
nuclease S1-PFGE analysis and transformation by electroporation into Escherichia
coli DH10B. Tn6297 contains an In27 class 1 integron harboring the dfrA12-orfF
aadA2 array, msr(E) and mph(E) associated with IS26; a new efflux pump multidrug
resistance composite transposon delimited by two ISEc29s; Tn-tet harboring tetR
and tetA(C); a class 1 integron with the qacG gene cassette; qnrVC6 and dfrA23
associated with ISCR1; and a complex class 1 integron In4-like containing aacC1,
aadA1, blaVEB-16, catA2, sul1Delta, cmlA9, tetR, tetA(G), aac(6')-II, and blaPSE
1. Its mer operon carries merB, but lacks merC, in contrast to Tn1696 and Tn21.
This study represents the first characterization of a multidrug-resistant
transposon and multidrug resistance plasmid in Shewanella and is the first report
of blaOXA-416 in Algeria, providing evidence that Shewanella spp. could be an
important reservoir and vehicle for drug resistance genes.
PMID- 27505639
TI - Spectrum of classes of point emitters: new tool for nonparaxial optical field
modeling.
AB - Numerical modeling of optical fields provides valuable support to both
theoretical research and technological development in many optics fields. Fourier
methods have been the most widely used tools of numerical modeling. However,
important limitations have restricted their application in contemporary research
that involve high numerical apertures, short propagation distances, and spatially
partially coherent states of light, for instance. The spectrum of classes of
point emitters is introduced as a numerical tool that overcomes such limitations
for the design, analysis, and synthesis of nonparaxial optical fields in
arbitrary states of spatial coherence. In this context, optical processing is
realized as the filtering on the spectrum of classes of point emitters performed
by the complex degree of spatial coherence that could be implemented dynamically
by using programmable devices.
PMID- 27505640
TI - Salient object detection fusing global and local information based on
nonsubsampled contourlet transform.
AB - The nonsubsampled contourlet transform (NSCT) has properties of multiresolution,
localization, directionality, and anisotropy. The directionality property permits
it to resolve intrinsic directional features that characterize the analyzed
image. In this paper, we present a bottom-up salient object detection approach
fusing global and local information based on NSCT. Images are first decomposed by
applying NSCT. The coefficients of bandpass subbands are categorized and
optimized accordingly to get better representation. Then feature maps are
obtained by performing the inverse NSCT on these optimized coefficients. The
global and local saliency maps are generated from these feature maps. Global
saliency is obtained by utilizing the likelihood of features, and local saliency
is measured by calculating the local self-information. In the end, the final
saliency map is computed by fusing the global and local saliency maps together.
Experimental results on MSRA 10K demonstrate the effectiveness and promising
performance of our proposed method.
PMID- 27505641
TI - Propagation properties of an optical vortex carried by a Bessel-Gaussian beam in
anisotropic turbulence.
AB - Rytov theory was employed to establish the transmission model for the optical
vortices carried by Bessel-Gaussian (BG) beams in weak anisotropic turbulence
based on the generalized anisotropic von Karman spectrum. The influences of
asymmetry anisotropic turbulence eddies and source parameters on the signal
orbital angular momentum (OAM) mode detection probability of partially coherent
BG beams in anisotropic turbulence were discussed. Anisotropic characteristics of
the turbulence could enhance the OAM mode transmission performance. The spatial
partially coherence of the beam source would increase turbulent aberration's
effect on the optical vortices. BG beams could dampen the influences of the
turbulence because of their nondiffraction and self-healing characteristics.
PMID- 27505642
TI - Average intensity and directionality of partially coherent model beams
propagating in turbulent ocean.
AB - We studied Gaussian beams with three different partially coherent models,
including the Gaussian-Schell model (GSM), Laguerre-Gaussian Schell model (LGSM),
and Bessel-Gaussian Schell model (BGSM), propagating through oceanic turbulence.
The expressions of average intensity, beam spreading, and beam wander for GSM,
LGSM, and BGSM beams in the paraxial channel are derived. We make a contrast for
the three models in numerical simulations and find that the GSM beam has smaller
spreading than the others, and the LGSM beam needs longer propagation distance to
transform into a well-like profile of average intensity than the BGSM beam in the
same conditions. The salinity fluctuation has a greater contribution to the
wander of LGSM and BGSM beams than that of the temperature fluctuation. Our
results can be helpful in the design of an optical wireless communication link
operating in oceanic environment.
PMID- 27505643
TI - Variational principle in optics II: Dissipative wave equations.
AB - The problem of phase retrieval from intensity measurements is examined for the
case of dissipative wave equations. Unlike the conservative case, it is not clear
if and when the problem is solvable at all. We provide two solutions. First, it
is shown that, for a certain class of dissipating potentials, the problem can be
fully solved by converting it through a simple transformation to the framework of
the weighted least action principle. Second, for all other dissipating
potentials, a deep result from the theory of elliptic partial differential
equations is used to show that the problem is always solvable up to a scaling of
one of the measured intensities. Moreover, the solution in this general case can
be obtained by solving a Monge-Ampere type differential equation. Two numerical
examples are given to illustrate some of the theoretical considerations.
PMID- 27505644
TI - Characteristic functionals in imaging and image-quality assessment: tutorial.
AB - Characteristic functionals are one of the main analytical tools used to quantify
the statistical properties of random fields and generalized random fields. The
viewpoint taken here is that a random field is the correct model for the ensemble
of objects being imaged by a given imaging system. In modern digital imaging
systems, random fields are not used to model the reconstructed images themselves
since these are necessarily finite dimensional. After a brief introduction to the
general theory of characteristic functionals, many examples relevant to imaging
applications are presented. The propagation of characteristic functionals through
both a binned and list-mode imaging system is also discussed. Methods for using
characteristic functionals and image data to estimate population parameters and
classify populations of objects are given. These methods are based on maximum
likelihood and maximum a posteriori techniques in spaces generated by sampling
the relevant characteristic functionals through the imaging operator. It is also
shown how to calculate a Fisher information matrix in this space. These
estimators and classifiers, and the Fisher information matrix, can then be used
for image quality assessment of imaging systems.
PMID- 27505645
TI - Spectral image analysis of mutual illumination between florescent objects.
AB - This paper proposes a method for modeling and component estimation of the
spectral images of the mutual illumination phenomenon between two fluorescent
objects. First, we briefly describe the bispectral characteristics of a single
fluorescent object, which are summarized as a Donaldson matrix. We suppose that
two fluorescent objects with different bispectral characteristics are located
close together under a uniform illumination. Second, we model the mutual
illumination between two objects. It is shown that the spectral composition of
the mutual illumination is summarized with four components: (1) diffuse
reflection, (2) diffuse-diffuse interreflection, (3) fluorescent self
luminescence, and (4) interreflection by mutual fluorescent illumination. Third,
we develop algorithms for estimating the spectral image components from the
observed images influenced by the mutual illumination. When the exact Donaldson
matrices caused by the mutual illumination influence are unknown, we have to
solve a non-linear estimation problem to estimate both the spectral functions and
the location weights. An iterative algorithm is then proposed to solve the
problem based on the alternate estimation of the spectral functions and the
location weights. In our experiments, the feasibility of the proposed method is
shown in three cases: the known Donaldson matrices, weak interreflection, and
strong interreflection.
PMID- 27505646
TI - Correction technology of a polarization lidar with a complex optical system.
AB - A complex optical system used in polarization lidars often modifies the input
polarization of the return signal so that it may significantly impact
depolarization estimates and introduce errors to polarization lidar measurements.
In most cases, retardation, depolarization, and misalignment of the system exist
at the same time and interact with each other. Polarization effects of the system
cannot be represented by a simple correction coefficient, so they cannot be
removed using a traditional calibration method. Detailed analysis and correction
technologies were provided to remove systematic biases in estimating
depolarization values from a polarization lidar owing to multiple optical
components. The Mueller matrices from an emitter to a receiver were calculated,
and the expression for an aerosol depolarization parameter including system
polarization effects was derived and obtained. In addition, the correction
algorithm based on the Mueller matrix was introduced and provided. A polarization
lidar was established, and the polarization characteristics of its optical
components were measured with a laboratory ellipsometer; then, the Mueller matrix
of the receiver was calculated and obtained. Lidar observations were performed,
and our correction algorithm was applied to lidar field data. The results show
that the correction method can significantly remove systematic polarization
effects.
PMID- 27505647
TI - Can spherical eukaryotic microalgae cells be treated as optically homogeneous?
AB - This study aims to answer the question of whether spherical unicellular
photoautotrophic eukaryotic microalgae cells, consisting of various intracellular
compartments with their respective optical properties, can be modeled as
homogeneous spheres with some effective complex index of refraction. The spectral
radiation characteristics in the photosynthetically active region of a spherical
heterogeneous microalgae cell, representative of Chlamydomonas reinhardtii and
consisting of spherical compartments corresponding to the cell wall, cytoplasm,
chloroplast, nucleus, and mitochondria, were estimated using the superposition T
matrix method. The effects of the presence of intracellular lipids and/or starch
accumulation caused by stresses, such as nitrogen limitation, were explored.
Predictions by the T-matrix method were qualitatively and quantitatively
consistent with experimental measurements for various microalgae species. The
volume-equivalent homogeneous sphere approximation with volume-averaged effective
complex index of refraction gave accurate estimates of the spectral (i)
absorption and (ii) scattering cross sections of the heterogeneous cells under
both nitrogen-replete and nitrogen-limited conditions. In addition, the effect of
a strongly refracting cell wall, representative of Chlorella vulgaris, was
investigated. In this case, for the purpose of predicting their integral
radiation characteristics, the microalgae should be represented as a coated
sphere with a coating corresponding to the cell wall and a homogeneous core with
volume-averaged complex index of refraction for the rest of the cell. However,
both homogeneous sphere and coated sphere approximations predicted strong
resonances in the scattering phase function and spectral backscattering cross
section that were not observed in that of the heterogeneous cells.
PMID- 27505648
TI - Reconstruction of an optical surface from a given source-target map.
AB - We propose a new method for the reconstruction of a reflecting (refracting)
surface from a given source-target map defining the relationships between the
directions of incident and reflected (refracted) rays. In the proposed method,
the optical surface is represented as an envelope of a set of paraboloids
(reflecting surface) or ellipsoids (refracting surface). This representation
allows the problem of design of an optical surface to be reduced to the
reconstruction of a function from its total differential. We illustrate the
proposed approach by designing mirrors generating a far-field uniform illuminance
in a square target. The calculation results show that the proposed method enables
the generation of high-quality illuminance distributions even when the
integrability condition is not satisfied.
PMID- 27505649
TI - Refined treatment of single-edge diffraction effects in radiometry.
AB - This work treats diffraction corrections in radiometry for cases of point and
extended sources in cylindrically symmetrical three-element systems. It considers
diffraction effects for spectral power and total power in cases of Planck
sources. It improves upon an earlier work by the author by giving a simpler
rendering of leading terms in asymptotic expansions for diffraction effects and
reliable estimates for the remainders. This work also demonstrates a framework
for accelerating the treatment of extended sources and simplifying the
calculation of diffraction effects over a range of wavelengths. This is
especially important in the short-wavelength region, where dense sampling of
wavelength values is in principle necessitated by the rapidly oscillatory
behavior of diffraction effects as a function of wavelength. We demonstrate the
methodology's efficacy in two radiometric applications.
PMID- 27505650
TI - Symmetric form-invariant dual Pearcey beams.
AB - We introduce another type of Pearcey beam, namely, dual Pearcey (DP) beams, based
on the Pearcey function of catastrophe theory. DP beams are experimentally
generated by applying Fresnel diffraction of bright elliptic rings. Form
invariant Bessel distribution beams can be regarded as a special case of DP
beams. Subsequently, the basic propagation characteristics of DP beams are
identified. DP beams are the result of the interference of two half DP beams
instead of two classical Pearcey beams. Moreover, we also verified that half DP
beams (including special-case parabolic-like beams) generated by half elliptical
rings (circular rings) are a new member of the family of form-invariant beams.
PMID- 27505651
TI - Spherical aberration in electrically thin flat lenses.
AB - We analyze the spherical aberration of a new generation of lenses made of flat
electrically thin inhomogeneous media. For such lenses, spherical aberration is
analyzed quantitatively and qualitatively, and comparison is made to the
classical gradient index rod. Both flat thin and thick lenses are made of
gradient index materials, but the physical mechanisms and design equations are
different. Using full-wave three-dimensional numerical simulation, we evaluate
the spherical aberrations using the Marechal criterion and show that the thin
lens gives significantly better performance than the thick lens (rod).
Additionally, based on ray tracing formulation, third-order analysis for
longitudinal aberration and optical path difference are presented, showing strong
overall performance of thin lenses in comparison to classical rod lenses.
PMID- 27505652
TI - First-order method of zoom lens design by means of generalized parameters.
AB - A method of paraxial zoom lens design is proposed that makes it possible to
determine the optical powers and component movements of a zoom lens with the
required zoom ratio. The method is based on the theory of generalized parameters,
which can be used to analyze a zoom system by varying only one parameter. All
possible zoom lenses with two movable components are considered for an object at
infinity.
PMID- 27505653
TI - Pupil dynamics with periodic flashes: effect of age on mesopic adaptation.
AB - The purpose of this study is to determine the pupillary dynamics with periodical
flashes from a peripheral glare source, in similar conditions to night driving,
while focusing on dependence with age. We measured two groups of people: youth
and adults. Maximum pupil size decreases due to periodic flashes. Latency does
not present significant differences. The reduction of pupil size is greater for
older adults. The presence of a peripheral and periodic glare source modifies the
pupil size. This leads to a reduction of retinal illuminance, which is greater
for older adults.
PMID- 27505654
TI - Optical Hall effect-model description: tutorial.
AB - The optical Hall effect is a physical phenomenon that describes the occurrence of
magnetic-field-induced dielectric displacement at optical wavelengths, transverse
and longitudinal to the incident electric field, and analogous to the static
electrical Hall effect. The electrical Hall effect and certain cases of the
optical Hall effect observations can be explained by extensions of the classic
Drude model for the transport of electrons in metals. The optical Hall effect is
most useful for characterization of electrical properties in semiconductors.
Among many advantages, while the optical Hall effect dispenses with the need of
electrical contacts, electrical material properties such as effective mass and
mobility parameters, including their anisotropy as well as carrier type and
density, can be determined from the optical Hall effect. Measurement of the
optical Hall effect can be performed within the concept of generalized
ellipsometry at an oblique angle of incidence. In this paper, we review and
discuss physical model equations, which can be used to calculate the optical Hall
effect in single- and multiple-layered structures of semiconductor materials. We
define the optical Hall effect dielectric function tensor, demonstrate
diagonalization approaches, and show requirements for the optical Hall effect
tensor from energy conservation. We discuss both continuum and quantum
approaches, and we provide a brief description of the generalized ellipsometry
concept, the Mueller matrix calculus, and a 4*4 matrix algebra to calculate data
accessible by experiment. In a follow-up paper, we will discuss strategies and
approaches for experimental data acquisition and analysis.
PMID- 27505655
TI - Analytical expression for pixel-averaged point sources as observed by a focal
plane array.
AB - A closed-form expression is derived for pixel-averaged point source signals as
observed by an imaging array. Obtaining this solution requires the probability
distribution of squared Euclidean distances in two dimensions when the end points
are confined to a uniformly spaced square domain. The derivation and associated
expression are provided.
PMID- 27505656
TI - Estimating individual cone fundamentals from their color-matching functions.
AB - Estimation of individual spectral cone fundamentals from color-matching functions
is a classical and longstanding problem in color science. In this paper we
propose a novel method to carry out this estimation based on a linear
optimization technique, employing an assumption of a priori knowledge of the
retinal absorptance functions. The result is an estimation of the combined
lenticular and macular filtration for an individual, along with the nine
coefficients in the linear combination that relates their color-matching
functions to their estimated spectral-cone fundamentals. We test the method on
the individual Stiles and Burch color-matching functions and derive cone
fundamental estimations for different viewing fields and matching experiment
repetition. We obtain cone-fundamental estimations that are remarkably similar to
those available in the literature. This suggests that the method yields results
that are close to the true fundamentals.
PMID- 27505657
TI - Toward omnidirectional and automated imaging system for measuring oceanic
whitecap coverage.
AB - Accurate measurements of oceanic whitecap coverage from whitecap images are
required for better understanding air-gas transfer and aerosol production
processes. However, this is a challenging task because whitecap patches are
formed immediately after a wave breaks and are spread over a wide area. The main
challenges in designing whitecaps imaging instrument are the small field of view
of the camera lens, processing huge numbers of images, recording data over long
time periods, and deployment difficulties in stormy conditions. This paper
describes the hardware design of a novel high-resolution optical instrument for
imaging oceanic whitecaps and the automated algorithm processing the collected
images. The instrument was successfully deployed in 2013 as part of the HiWINGS
campaign in the North Atlantic Ocean. The instrument uses a fish-eye camera lens
to image the whitecaps in a wide angle of view (180 degrees ).
PMID- 27505658
TI - Eye movements and information geometry.
AB - The human visual system uses eye movements to gather visual information. They act
as visual scanning processes and can roughly be divided into two different types:
small movements around fixation points and larger movements between fixation
points. The processes are often modeled as random walks, and recent models based
on heavy tail distributions, also known as Levy flights, have been used in these
investigations. In contrast to these approaches we do not model the stochastic
processes, but we will show that the step lengths of the movements between
fixation points follow generalized Pareto distributions (GPDs). We will use
general arguments from the theory of extreme value statistics to motivate the
usage of the GPD and show empirically that the GPDs provide good fits for
measured eye tracking data. In the framework of information geometry the GPDs
with a common threshold form a two-dimensional Riemann manifold with the Fisher
information matrix as a metric. We compute the Fisher information matrix for the
GPDs and introduce a feature vector describing a GPD by its parameters and
different geometrical properties of its Fisher information matrix. In our
statistical analysis we use eye tracker measurements in a database with 15
observers viewing 1003 images under free-viewing conditions. We use Matlab
functions with their standard parameter settings and show that a naive Bayes
classifier using the eigenvalues of the Fisher information matrix provides a high
classification rate identifying the 15 observers in the database.
PMID- 27505659
TI - Foucault test: a quantitative evaluation method.
AB - Reliable and accurate testing methods are essential to guiding the polishing
process during the figuring of optical telescope mirrors. With the natural
advancement of technology, the procedures and instruments used to carry out this
delicate task have consistently increased in sensitivity, but also in complexity
and cost. Fortunately, throughout history, the Foucault knife-edge test has shown
the potential to measure transverse aberrations in the order of the wavelength,
mainly when described in terms of physical theory, which allows a quantitative
interpretation of its characteristic shadowmaps. Our previous publication on this
topic derived a closed mathematical formulation that directly relates the knife
edge position with the observed irradiance pattern. The present work addresses
the quite unexplored problem of the wavefront's gradient estimation from
experimental captures of the test, which is achieved by means of an optimization
algorithm featuring a proposed ad hoc cost function. The partial derivatives
thereby calculated are then integrated by means of a Fourier-based algorithm to
retrieve the mirror's actual surface profile. To date and to the best of our
knowledge, this is the very first time that a complete mathematical-grounded
treatment of this optical phenomenon is presented, complemented by an image
processing algorithm which allows a quantitative calculation of the corresponding
slope at any given point of the mirror's surface, so that it becomes possible to
accurately estimate the aberrations present in the analyzed concave device just
through its associated foucaultgrams.
PMID- 27505660
TI - Unwrapped wavefront evaluation in phase-shifting interferometry based on 3D
dynamic fringe processing in state space.
AB - Recovery of an unwrapped wavefront in phase-shifting interferometry is considered
when the wavefront phase increments are determined between previous and
subsequent fringe patterns as well as between adjacent pixels of the current
fringe pattern. A parametric model of a three-dimensional interferometric signal
and the recurrence processing algorithm in state space are utilized, providing an
evaluation of an unwrapped wavefront phase at each phase shift step in dynamic
mode. Estimates of the achievable accuracy and experimental results of the
wavefront recovery are presented. Comparison with the conventional seven-frame
phase-shifting algorithm, which is one of the most accurate, confirmed the high
accuracy and noise immunity of the proposed method.
PMID- 27505661
TI - Relating wavefront error, apodization, and the optical transfer function: on-axis
case: comment.
AB - In a recent paper [J. Opt. Soc. Am. A31, 2476 (2014)JOAOD60740
323210.1364/JOSAA.31.002476], a linear expansion of the optical transfer function
(OTF) of an imaging system in which the expansion coefficients are related to its
wavefront errors has been developed. It is claimed that the OTF can be calculated
quickly by using this approach. We provide instead closed-form basis functions
that are not determined recursively. Numerical examples demonstrate that the OTF
calculation by a digital autocorrelation of the pupil function is much faster
regardless of the wavefront complexity.
PMID- 27505662
TI - Relating wavefront error, apodization, and the optical transfer function: on-axis
case: reply.
AB - Efficient coding enables rapid calculation of basis functions for a linear
expansion of the optical transfer function.
PMID- 27505663
TI - Performance evaluation of modulation and multiple access schemes in ultraviolet
optical wireless connections for two atmosphere thickness cases.
AB - The exploitation of optical wireless communication channels in a non-line-of
sight regime is studied for point-to-point and networking configurations
considering the use of light-emitting diodes. Two environments with different
scattering center densities are considered, assuming operation at 265 nm. The bit
error rate performance of both pulsed and multicarrier modulation schemes is
examined, using numerical approaches. In the networking scenario, a central node
only receives data, one node transmits useful data, and the rest of them act as
interferers. The performance of the desirable node's transmissions is evaluated.
The access to the medium is controlled by a code division multiple access scheme.
PMID- 27505664
TI - Single-order transmission diffraction gratings based on dispersion engineered all
dielectric metasurfaces.
AB - A single-order transmission diffraction grating based on dispersion engineered
all-dielectric metasurfaces is proposed, and its wavelength discriminating
properties have been theoretically described and confirmed using numerical
simulations. The metasurface is designed using a 2D array of all-dielectric
resonators, which emulates a Huygens' source configuration to achieve a perfect
match to free space in broad bandwidth. Using a holey dielectric nanodisk
structure as the unit cell, the resonant wavelength is tapered across the
metasurface to engineer the wavelength-dependent spatial phase gradient, to
emulate a dispersive prism. Consequently, different wavelengths are steered
toward different directions and thus are discriminated on the output image plane.
Due to the subwavelength periodicities involved, wavelength discrimination is
achieved directly in the zeroth diffraction order of the device, unlike
conventional diffraction gratings, thereby providing a high-efficiency wavelength
discriminating device.
PMID- 27505665
TI - Combinatorial Tethering: A Novel Mode to Recruit Non-canonical PRC1 for Normal
and Malignant GC B Cell Development.
AB - Polycomb repressive complexes (PRCs) are key to normal development and are
frequently deregulated in human cancer. In this issue of Cancer Cell, Beguelin et
al. report a mechanism of non-canonical PRC1 recruitment by BCL6 in collaboration
with EZH2-mediated H3K27me3 for establishment of stable repressive complexes in
germinal center B cells.
PMID- 27505666
TI - Functionally Assessing Candidate Drivers Advances Precision Cancer Medicine.
AB - The complexity of genomic alterations in cancer has made it difficult to identify
oncogenic drivers for the development of targeted therapies. The study by Berger
et al. in this issue of Cancer Cell demonstrates that high-throughput functional
profiling can uncover impactful mutations and oncogenic driver alleles.
PMID- 27505667
TI - Pre-Metastatic Niche Formation Has Taken Its TOLL.
AB - Pre-Metastatic Niches (PMNs) result from communications between primary tumors
and the microenvironment of future distant metastasis via tumor-derived factors.
In this issue of Cancer Cell, Liu et al. show that TLR3 activation in lung
epithelial cells by tumor exosomal RNAs triggers neutrophil recruitment, which
contributes to PMN formation and metastasis.
PMID- 27505668
TI - IDH1, Histone Methylation, and So Forth.
AB - IDH mutants cause aberrant DNA and histone methylation and contribute to
hematological and neuronal malignancies. In this issue of Cancer Cell, Inoue et
al. describe a potential specific effect of IDH1 mutations that reduces Atm
expression via inhibition of H3K9 demethylases, which may represent a first step
toward cellular transformation.
PMID- 27505669
TI - Sticking It to Cancer with Molecular Glue for SHP2.
AB - Much effort has been expended to develop inhibitors against protein-tyrosine
phosphatases (PTPs), nearly all of it unsuccessful. A recent report, describing a
highly specific, orally bioavailable inhibitor of the PTP oncoprotein SHP2 with
in vivo activity, suggests that allostery might provide a way forward for PTP
inhibitor development.
PMID- 27505670
TI - EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent
Promoters, Mediate Germinal Center Formation and Lymphomagenesis.
AB - The EZH2 histone methyltransferase mediates the humoral immune response and
drives lymphomagenesis through formation of bivalent chromatin domains at
critical germinal center (GC) B cell promoters. Herein we show that the actions
of EZH2 in driving GC formation and lymphoma precursor lesions require site
specific binding by the BCL6 transcriptional repressor and the presence of a non
canonical PRC1-BCOR-CBX8 complex. The chromodomain protein CBX8 is induced in GC
B cells, binds to H3K27me3 at bivalent promoters, and is required for stable
association of the complex and the resulting histone modifications. Moreover,
oncogenic BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma
(DLBCL) development and combinatorial targeting of these repressors results in
enhanced anti-lymphoma activity in DLBCLs.
PMID- 27505671
TI - Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating
Alveolar Epithelial TLR3 to Recruit Neutrophils.
AB - The pre-metastatic niche educated by primary tumor-derived elements contributes
to cancer metastasis. However, the role of host stromal cells in metastatic niche
formation and organ-specific metastatic tropism is not clearly defined. Here, we
demonstrate that lung epithelial cells are critical for initiating neutrophil
recruitment and lung metastatic niche formation by sensing tumor exosomal RNAs
via Toll-like receptor 3 (TLR3). TLR3-deficient mice show reduced lung metastasis
in the spontaneous metastatic models. Mechanistically, primary tumor-derived
exosomal RNAs, which are enriched in small nuclear RNAs, activate TLR3 in lung
epithelial cells, consequently inducing chemokine secretion in the lung and
promoting neutrophil recruitment. Identification of metastatic axis of tumor
exosomal RNAs and host lung epithelial cell TLR3 activation provides potential
targets to control cancer metastasis to the lung.
PMID- 27505672
TI - Mitochondrial Akt Regulation of Hypoxic Tumor Reprogramming.
AB - Hypoxia is a universal driver of aggressive tumor behavior, but the underlying
mechanisms are not completely understood. Using a phosphoproteomics screen, we
now show that active Akt accumulates in the mitochondria during hypoxia and
phosphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the
pyruvate dehydrogenase complex. In turn, this pathway switches tumor metabolism
toward glycolysis, antagonizes apoptosis and autophagy, dampens oxidative stress,
and maintains tumor cell proliferation in the face of severe hypoxia.
Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic markers
and shorter survival in glioma patients and may provide an "actionable"
therapeutic target in cancer.
PMID- 27505673
TI - Regulation of OGT by URI in Response to Glucose Confers c-MYC-Dependent Survival
Mechanisms.
AB - Cancer cells can adapt and survive under low nutrient conditions, but underlying
mechanisms remain poorly explored. We demonstrate here that glucose maintains a
functional complex between the co-chaperone URI, PP1gamma, and OGT, the enzyme
catalyzing O-GlcNAcylation. Glucose deprivation induces the activation of PKA,
which phosphorylates URI at Ser-371, resulting in PP1gamma release and URI
mediated OGT inhibition. Low OGT activity reduces O-GlcNAcylation and promotes c
MYC degradation to maintain cell survival. In the presence of glucose, PP1gamma
bound URI increases OGT and c-MYC levels. Accordingly, mice expressing non
phosphorylatable URI (S371A) in hepatocytes exhibit high OGT activity and c-MYC
stabilization, accelerating liver tumorigenesis in agreement with c-MYC oncogenic
functions. Our work uncovers that URI-regulated OGT confers c-MYC-dependent
survival functions in response to glucose fluctuations.
PMID- 27505674
TI - Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2
Autoregulatory Loop in Multiple Myeloma Development.
PMID- 27505675
TI - Loss of the Par3 Polarity Protein Promotes Breast Tumorigenesis and Metastasis.
PMID- 27505676
TI - A Critical Role for Notch Signaling in the Formation of Cholangiocellular
Carcinomas.
PMID- 27505677
TI - Small Molecule Inhibitors of Aurora-A Induce Proteasomal Degradation of N-Myc in
Childhood Neuroblastoma.
PMID- 27505678
TI - A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis.
PMID- 27505679
TI - Wip1 Controls Global Heterochromatin Silencing via ATM/BRCA1-Dependent DNA
Methylation.
PMID- 27505680
TI - DNMT3A Loss Drives Enhancer Hypomethylation in FLT3-ITD-Associated Leukemias.
PMID- 27505682
TI - The Multifaceted Role of Perivascular Macrophages in Tumors.
PMID- 27505683
TI - Gaining insights from social media language: Methodologies and challenges.
AB - Language data available through social media provide opportunities to study
people at an unprecedented scale. However, little guidance is available to
psychologists who want to enter this area of research. Drawing on tools and
techniques developed in natural language processing, we first introduce
psychologists to social media language research, identifying descriptive and
predictive analyses that language data allow. Second, we describe how raw
language data can be accessed and quantified for inclusion in subsequent
analyses, exploring personality as expressed on Facebook to illustrate. Third, we
highlight challenges and issues to be considered, including accessing and
processing the data, interpreting effects, and ethical issues. Social media has
become a valuable part of social life, and there is much we can learn by bringing
together the tools of computer science with the theories and insights of
psychology. (PsycINFO Database Record
PMID- 27505684
TI - Split face evaluation of long-pulsed non-ablative 1,064 nm Nd:YAG laser for
treatment of direct browplasty scars.
AB - PURPOSE: To investigate 1,064 nm long-pulse Nd:YAG laser for postoperative
treatment of direct browplasty scars. METHODS: Nine patients who underwent direct
browplasty were enrolled in this prospective study. Subjects were randomized to
unilateral laser treatment at 2-week intervals for six total treatments, with the
contralateral scar used as a control. Prior to each treatment, subjects rated
treated and control scars on overall cosmesis. Post-treatment, subjects rated
each for erythema, swelling, discomfort, and perceived hair loss. Finally,
examiners masked to treatment side were asked to judge side-by-side photographs
of first and final visits for improvement and side effects. RESULTS: Subjects
rated the overall appearance of the treated scar significantly higher at the time
of treatment number 5 (mean score 5.13 +/- 2.03, P = 0.008) and treatment number
6 (6.25 +/- 1.98, P = 0.005) compared to treatment 1 (3.75 +/- 2.12); by
contrast, they failed to rate the control scar more highly. On masked examination
of photographs, the treated scar was selected as most improved 50.0 +/- 12.5% of
the time. Both subjects and graders reported side effects as transient and mild
to moderate (mean score 1-4), with no reports of hair loss from either subjects
or observers. CONCLUSIONS: The 1,064 nm Nd:YAG laser provided significant
improvement in scar cosmesis after direct browplasty, as rated by subject self
report, but not by masked observers, and appears to be a useful tool for
increasing satisfaction among those dissatisfied with direct browplasty scars.
Side effects-including erythema, edema, and discomfort-were transient and
universally rated as mild to moderate. Lasers Surg. Med. 48:742-747, 2016. (c)
2016 Wiley Periodicals, Inc.
PMID- 27505681
TI - Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma.
PMID- 27505685
TI - Canine and feline lymphoma: challenges and opportunities for creating a paradigm
shift.
PMID- 27505686
TI - Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides.
AB - Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium
falciparum identified a series of dihydroisoquinolones that possessed potent
antimalarial activity against multiple resistant strains of P. falciparum in
vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity
studies revealed relationships between potency and modifications at N-2, C-3, and
C-4. Careful structure-property relationship studies, coupled with studies of
metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as
well as potential toxicological effects, inherent in the more potent primary
screening hits such as 10b. Analogues 13h and 13i, with structural modifications
at each site, were shown to possess excellent antimalarial activity in vivo. The
(+)-(3S,4S) enantiomer of 13i and similar analogues were identified as the more
potent. On the basis of these studies, we have selected (+)-13i for further study
as a preclinical candidate.
PMID- 27505687
TI - Water Diffusion from a Bacterial Cell in Low-Moisture Foods.
AB - We used a Fick's unsteady state diffusion equation to estimate the time required
for a single spherical shaped bacterium (assuming Enterococcus faecium as the
target microorganism) in low-moisture foods to equilibrate with the environment.
We generated water sorption isotherms of freeze-dried E. faecium. The water
activity of bacterial cells at given water content increased considerably as
temperature increased from 20 to 80 degrees C, as observed in the sorption
isotherms of bacterial cells. When the water vapor diffusion coefficient was
assumed as between 10(-12) and 10(-10) m(2) /s for bacterial cells, the predicted
equilibration times (teq ) ranged from 8.24*10(-4) to 8.24*10(-2) s. Considering
a cell membrane barrier with a lower water diffusion coefficient (10(-15) m(2)
/s) around the bacterial cell with a water diffusion coefficient of 10(-12) m(2)
/s, the teq predicted using COMSOL Multiphysics program was 3.8*10(-1) s. This
result suggests that a single bacterium equilibrates rapidly (within seconds)
with change in environmental humidity and temperature.
PMID- 27505688
TI - High level of serum human interleukin-18 in a patient with pyogenic arthritis,
pyoderma gangrenosum and acne syndrome.
PMID- 27505689
TI - Biogeography as critical nursing pedagogy: Breathing life into nurse education.
AB - Insights from the social sciences, including geography, sociology, and
anthropology, have long been incorporated into pre-registration nursing
programmes. However, scholars have suggested that their inclusion has been
sporadic and lacks clear theoretical rationale. In this paper we argue anew that
the social sciences - and particularly, human geography - could be central to
nurse education. Specifically, we recast the concept of 'biogeography' drawn from
human geography that emphasises the interplay between life (bio) and place (geo)
to propose pedagogy that theoretically justifies and practically enables the
inclusion of the social sciences in nurse education. Biogeography can breathe new
life into nursing curricula by animating our students through the cultivation of
three 'spirits of nursing'. First, a 'spirit of empathy' that can shatter patient
professional dualisms by facilitating person-centred and place-sensitive care.
Second, a 'spirit of engagement' that situates practice in social structures
awakening a desire to effect change by fomenting an acute sense of social
justice. Third, a 'spirit of enquiry' that holds in critical tension the theory
practice gap by fostering continual questioning and pursuit of evidence. In so
doing, biogeographical pedagogy releases the latent potential of the social
sciences to revitalise nurse education, reinvigorate our students, and renew
ourselves as nurse educators.
PMID- 27505690
TI - Clinician's Commentary on Stratford and Riddle(1).
PMID- 27505691
TI - Photochemical Stereocontrol Using Tandem Photoredox-Chiral Lewis Acid Catalysis.
AB - The physical, biological, and materials properties of organic compounds are
determined by their three-dimensional molecular shape. The development of methods
to dictate the stereochemistry of organic reactions has consequently emerged as
one of the central themes of contemporary synthetic chemistry. Over the past
several decades, chiral catalysts have been developed to control the
enantioselectivity of almost every class of synthetically useful transformation.
Photochemical reactions, however, are a conspicuous exception. Relatively few
examples of highly enantioselective catalytic photoreactions have been reported
to date, despite almost a century of research in this field. The development of
robust strategies for photochemical enantiocontrol has thus proven to be a long
standing and surprisingly difficult challenge. For the past decade, our
laboratory has been studying the application of transition metal photocatalysts
to a variety of problems in synthetic organic chemistry. These efforts have
recently culminated in the discovery of an effective system in which the activity
of a visible light absorbing transition metal photoredox catalyst is combined
with a second stereocontrolling chiral Lewis acid catalyst. This dual catalyst
strategy has been applied to a diverse range of photochemical reactions; these
have included highly enantioselective photocatalytic [2 + 2] cycloadditions, [3 +
2] cycloadditions, and radical conjugate addition reactions. This Account
describes the development of the tandem Lewis acid photoredox catalysis strategy
utilized in our laboratory. It provides an analysis of the factors that we
believe to be particularly important to the success of this seemingly robust
approach to photocatalytic stereocontrol. (1) The photocatalysts utilized in our
systems are activated by wavelengths of visible light where the organic
substrates are transparent, which minimizes the possibility of competitive
racemic background photoreactions. (2) The high degree of tolerance that
Ru(bpy)32+ and similar octahedral metal polypyridine complexes exhibit toward
Lewis acids affords great flexibility in tuning the structure of the
stereocontrolling chiral catalyst without perturbing the photoredox properties of
the photocatalyst. (3) Synthetic chemists have amassed a substantial
understanding of the features that are common in highly successful chiral Lewis
acid catalyzed reactions, and these deep, well-validated insights are readily
applied to the reactions of a variety of photogenerated intermediates. We hope
that the recent success of this and similar dual catalytic systems will provide a
useful foundation for the further development of powerful, stereocontrolled
photochemical reactions.
PMID- 27505693
TI - Maternal behavior predicts infant neurophysiological and behavioral attention
processes in the first year.
AB - We apply a biopsychosocial conceptualization to attention development in the 1st
year and examine the role of neurophysiological and social processes on the
development of early attention processes. We tested whether maternal behavior
measured during 2 mother-child interaction tasks when infants (N = 388) were 5
months predicted infant medial frontal (F3/F4) EEG power and observed attention
behavior during an attention task at 10 months. After controlling for infant
attention behavior and EEG power in the same task measured at an earlier 5-month
time point, results indicated a significant direct and positive association from
5-month maternal positive affect to infant attention behavior at 10 months.
However, maternal positive affect was not related to medial frontal EEG power. In
contrast, 5-month maternal intrusive behavior was associated with infants' task
related EEG power change at the left frontal location, F3, at 10 months of age.
The test of indirect effects from 5-month maternal intrusiveness to 10-month
infant attention behavior via infants' EEG power change at F3 was significant.
These findings suggest that the development of neural networks serving attention
processes may be 1 mechanism through which early maternal behavior is related to
infant attention development in the 1st year and that intrusive maternal behavior
may have a particularly disruptive effect on this process. (PsycINFO Database
Record
PMID- 27505694
TI - The role of age, working memory, and response inhibition in deviance distraction:
A cross-sectional study.
AB - Sounds deviating from an otherwise repeated or structured sequence capture
attention and affect performance in an ongoing visual task negatively, testament
to the balance between selective attention and change detection. Although
deviance distraction has been the object of much research, its modulation across
the life span has been more scarcely addressed. Recent findings suggest possible
connections with working memory and response inhibition. In this study we
measured the performance of children and young and older adults in a cross-modal
oddball task (deviance distraction), a working memory task (working memory
capacity), and a response inhibition task (ability to voluntarily inhibit an
already planned action) with the aim to establish the contribution of the latter
2 to the first. Older adults exhibited significantly more deviance distraction
than children and young adults (who did not differ from each other). Working
memory capacity mediated deviance distraction in children and older adults
(though in opposite directions) but not in young adults. Response inhibition
capacities did not mediate deviance distraction in any of the age groups.
Altogether the results suggest that although the increase in deviance distraction
observed in old age may partly reflect the relative impairment of working memory
mechanisms, there is no straightforward and stable relation between working
memory capacity and deviance distraction across the life span. Furthermore, our
results indicate that deviance distraction is unlikely to reflect the temporary
inhibition of responses. (PsycINFO Database Record
PMID- 27505695
TI - Emotional interactions in European American mother-infant firstborn and
secondborn dyads: A within-family study.
AB - The developmental science literature is riven with respect to (a) parental
similar versus different treatment of siblings and (b) sibling similarities and
differences. Most methodologies in the field are flawed or confounded. To address
these issues, this study employed a within-family longitudinal design to examine
developmental processes of continuity and stability in emotional interactions in
mothers with their firstborn and secondborn 5-month-old infants (ns = 61 mothers
and 122 infants). As independently rated by the Emotional Availability Scales,
mothers' observed and coded behavioral expressions of sensitivity, structuring,
nonintrusiveness, and nonhostility were consistent in group mean levels between
firstborns and secondborns and (largely) between daughters and sons. Neither
firstborns and secondborns, nor girls and boys, differed in their responsiveness
or involvement of mother. However, mothers' emotional interactions with their
firstborn and secondborn children were uncorrelated, as were firstborn and
secondborn infants' interactions with their mother. These group-mean
consistencies and individual-differences inconsistencies in emotional
interactions are discussed in relation to the shared and nonshared lives of
siblings in the same family. (PsycINFO Database Record
PMID- 27505692
TI - The Enzymology of Organic Transformations: A Survey of Name Reactions in
Biological Systems.
AB - Chemical reactions that are named in honor of their true, or at least perceived,
discoverers are known as "name reactions". This Review is a collection of
biological representatives of named chemical reactions. Emphasis is placed on
reaction types and catalytic mechanisms that showcase both the chemical diversity
in natural product biosynthesis as well as the parallels with synthetic organic
chemistry. An attempt has been made, whenever possible, to describe the enzymatic
mechanisms of catalysis within the context of their synthetic counterparts and to
discuss the mechanistic hypotheses for those reactions that are currently active
areas of investigation. This Review has been categorized by reaction type, for
example condensation, nucleophilic addition, reduction and oxidation,
substitution, carboxylation, radical-mediated, and rearrangements, which are
subdivided by name reactions.
PMID- 27505696
TI - The development of adaptive decision making: Recognition-based inference in
children and adolescents.
AB - Judgments about objects in the world are often based on probabilistic information
(or cues). A frugal judgment strategy that utilizes memory (i.e., the ability to
discriminate between known and unknown objects) as a cue for inference is the
recognition heuristic (RH). The usefulness of the RH depends on the structure of
the environment, particularly the predictive power (validity) of recognition.
Little is known about developmental differences in use of the RH. In this study,
the authors examined (a) to what extent children and adolescents recruit the RH
when making judgments, and (b) around what age adaptive use of the RH emerges.
Primary schoolchildren (M = 9 years), younger adolescents (M = 12 years), and
older adolescents (M = 17 years) made comparative judgments in task environments
with either high or low recognition validity. Reliance on the RH was measured
with a hierarchical multinomial model. Results indicated that primary
schoolchildren already made systematic use of the RH. However, only older
adolescents adaptively adjusted their strategy use between environments and were
better able to discriminate between situations in which the RH led to correct
versus incorrect inferences. These findings suggest that the use of simple
heuristics does not progress unidirectionally across development but strongly
depends on the task environment, in line with the perspective of ecological
rationality. Moreover, adaptive heuristic inference seems to require experience
and a developed base of domain knowledge. (PsycINFO Database Record
PMID- 27505698
TI - Why do some adolescents encounter everyday events that increase their civic
interest whereas others do not?
AB - Using a longitudinal design, we asked 2 age cohorts of adolescents (15- and 18
year-olds) whether they, during the last year, had experienced events that had
increased their civic interest and about details of their experiences. Based on
self-determination theory, we predicted that the adolescents who reported having
experienced events of this kind had already been more interested and had had more
positive feelings about politics much earlier in time, and that this original
interest would have increased more over time, than that of other adolescents.
Second, we proposed that the adolescents who had encountered events that
triggered their civic interest would have been engaged in behaviors that
reflected their needs for autonomy, relatedness, and competence, much earlier in
time, and that, over time, they would have increased these behaviors more than
other adolescents. These 2 predictions were largely confirmed. As for the content
of the events the adolescents reported, many of them concerned national and
international issues experienced as threatening, and that challenged the
adolescents' beliefs and morality. Overall, a previous interest in politics and
engagement in exploratory behaviors that reflect the adolescents' psychological
needs seem to play crucial roles in understanding why adolescents in their
everyday life encounter events that trigger their civic interest. Further, the
findings show that having had everyday experiences that trigger the adolescents'
civic interests are associated with a later increase in political interest more
broadly. (PsycINFO Database Record
PMID- 27505697
TI - Little relation of adult age with cognition after controlling general influences.
AB - Both general (i.e., shared across different cognitive measures) and specific
(i.e., unique to particular cognitive measures) influences can be postulated to
contribute to the relations between adult age and measures of cognitive
functioning. Estimates of general and specific influences on measures of memory,
speed, reasoning, and spatial visualization were derived in cross-sectional (N =
5,014) and 3-occasion longitudinal (N = 1,353) data in adults between 18 and 99
years of age. Increased age was negatively associated with estimates of general
influences on cognitive functioning in both the cross-sectional differences and
the longitudinal changes. Furthermore, after statistically controlling general
influences, the relations of age on the cognitive measures were much smaller than
were those in the original measures. Results from these and other analytical
procedures converge on the conclusion that adult age appears to have weak
relations with specific measures of cognitive functioning, defined as independent
of influences shared across different types of cognitive measures, and that this
is true in both cross-sectional and longitudinal comparisons. An implication of
these findings is that general, as well as domain-specific, influences should be
considered when attempting to explain the relations of age on cognitive
functioning. (PsycINFO Database Record
PMID- 27505699
TI - Generics license 30-month-olds' inferences about the atypical properties of novel
kinds.
AB - We examined whether the distinction between generic and nongeneric language
provides toddlers with a rapid and efficient means to learn about kinds. In
Experiment 1, we examined 30-month-olds' willingness to extend atypical
properties to members of an unfamiliar category when the properties were
introduced in 1 of 3 ways: (a) using a generic noun phrase ("Blicks drink
ketchup"); (b) using a nongeneric noun phrase ("These blicks drink ketchup"); and
(c) using an attentional phrase ("Look at this"). Hearing a generic noun phrase
boosted toddlers' extension of properties to both the model exemplars and to
novel members of the same category, relative to when a property had been
introduced with a nongeneric noun phrase or an attentional phrase. In Experiment
2, properties were introduced with a generic noun phrase, and toddlers extended
novel properties to members of the same-category, but not to an out-of-category
object. Taken together, these findings demonstrate that generics highlight the
stability of a feature and foster generalization of the property to novel within
category exemplars. (PsycINFO Database Record
PMID- 27505700
TI - Fadeout in an early mathematics intervention: Constraining content or preexisting
differences?
AB - A robust finding across research on early childhood educational interventions is
that the treatment effect diminishes over time, with children not receiving the
intervention eventually catching up to children who did. One popular explanation
for fadeout of early mathematics interventions is that elementary school teachers
may not teach the kind of advanced content that children are prepared for after
receiving the intervention, so lower-achieving children in the control groups of
early mathematics interventions catch up to the higher-achieving children in the
treatment groups. An alternative explanation is that persistent individual
differences in children's long-term mathematical development result more from
relatively stable preexisting differences in their skills and environments than
from the direct effects of previous knowledge on later knowledge. We tested these
2 hypotheses using data from an effective preschool mathematics intervention
previously known to show a diminishing treatment effect over time. We compared
the intervention group to a matched subset of the control group with a similar
mean and variance of scores at the end of treatment. We then tested the relative
contributions of factors that similarly constrain learning in children from
treatment and control groups with the same level of posttreatment achievement and
preexisting differences between these 2 groups to the fadeout of the treatment
effect over time. We found approximately 72% of the fadeout effect to be
attributable to preexisting differences between children in treatment and control
groups with the same level of achievement at posttest. These differences were
fully statistically attenuated by children's prior academic achievement.
(PsycINFO Database Record
PMID- 27505701
TI - Social engagement and adaptive functioning during early childhood: Identifying
and distinguishing among subgroups differing with regard to social engagement.
AB - This study tested the hypothesis that social engagement (SE) with peers is a
fundamental aspect of social competence during early childhood. Relations between
SE and a set of previously validated social competence indicators, as well as
additional variables derived from observation and sociometric interviews were
assessed using both variable-centered and person-centered approaches (N = 1453,
696 girls) in 4 samples (3 U.S.A., 1 Portuguese). Directly observed SE was
positively associated with broad-band measures of socially competent behavior,
peer acceptance, being a target of peers' attention, and also with broad-band
personality dimensions. Using individual Q-items significantly associated with SE
in 3 of our 4 samples, a hierarchical cluster analysis yielded a 5-cluster
solution that grouped cases efficiently. Tests on relations between cluster
membership and the set of social competence and other variables revealed
significant main effects of cluster membership in the full sample and within each
individual sample, separately. With the exception of tests for peer negative
preference, children in the lowest SE cluster also had significantly lower
overall social competence, personality functioning scores than did children in
higher SE clusters. (PsycINFO Database Record
PMID- 27505702
TI - Maternal scaffolding and home stimulation: Key mediators of early intervention
effects on children's cognitive development.
AB - This study contributes to the understanding of how early parenting interventions
implemented in low- and middle-income countries during the first 2 years of
children's lives are sustained longitudinally to promote cognitive skills in
preschoolers. We employed path analytic procedures to examine 2 family processes
the quality of home stimulation and maternal scaffolding behaviors-as underlying
mechanisms through which a responsive stimulation intervention uniquely predicted
children's verbal intelligence, performance intelligence, and executive
functioning. The sample included 1,302 highly disadvantaged children and their
mothers living in rural Pakistan, who from birth participated in a 2-year,
community-based, cluster-randomized, controlled trial designed to promote
sensitive and responsive caregiving. Family processes were assessed at 2
developmental time points using parent reports, ratings of home environments, and
observed parent-child interactions. Cognitive skills at age 4 were assessed using
standardized tests. Controlling for socioeconomic risk (e.g., wealth, maternal
education, food insecurity) and individual factors (e.g., gender, growth status),
the quality of current home stimulation as well as both earlier and concurrent
measures of maternal scaffolding independently mediated the intervention effects
on cognitive skills at age 4. In addition, the intervention had a significant
direct effect on executive functioning and performance intelligence over and
above significant family processes and other covariates. We highlight
implications for future program design and evaluation studies. (PsycINFO Database
Record
PMID- 27505703
TI - The Academy of Breastfeeding Medicine's Communications Committee.
PMID- 27505704
TI - Multimodality Imaging of Neurodegenerative Processes: Part 1, The Basics and
Common Dementias.
AB - OBJECTIVE: Multimodality imaging plays an important role in the structural and
functional characterization of neurodegenerative conditions. This article
illustrates the basic concepts of anatomic, metabolic, and amyloid imaging and
describes the application of a multimodality approach in the evaluation of
patients with the more common neurodegenerative dementia processes. Proper
utilization of clinically available imaging techniques allows greater insight
into these common disease processes. CONCLUSION: Recognizing the strength of
combined anatomic, metabolic, and amyloid imaging can allow a more complete and
confident assessment of patients with common degenerative dementias. This added
knowledge can improve clinical care, allow initiation of appropriate therapies
and counseling, and improve prognostication.
PMID- 27505705
TI - Phase I study of azacitidine following donor lymphocyte infusion for relapsed
acute myeloid leukemia post allogeneic stem cell transplantation.
AB - Donor lymphocyte infusion (DLI) without prophylactic immunosuppression has been
used for relapsed AML after allogeneic stem cell transplant (allo-SCT). However
DLI is associated with an increased incidence of acute Graft vs. Host Disease
(aGVHD). In mice, administration of azacitidine (AzaC) on days 4, 6, 8, and 10
post DLI increases regulatory T cell (Treg) numbers and prevents GVHD without
hindering Graft vs. Leukemia (GVL). Based on these findings, we conducted a phase
1 study of AzaC post DLI for AML relapse post allo-SCT. AzaC was administered on
days 4, 6, 8 and 10 post-DLI. Dose escalation was done using a 3+3 design with
three AzaC dose levels: 30mg/m(2) (level -1), 45mg/m(2) (level 1) and 75mg/m(2)
(level 2). Three patients were treated in the 45mg/m(2) dose level and 5 patients
were treated in the 75mg/m(2) dose level; no DLTs or grade 3-5 treatment related
toxicities were observed. After a median follow-up of 5.2 months, no patients
developed grade III-IV aGVHD and no patients died of aGVHD. Six out of 8 patients
in the treatment group responded to treatment including two cytogenetic complete
remissions, one hematologic complete remission, and three complete remissions
with incomplete count recovery. In conclusion, administration of AzaC early post
DLI is well tolerated and can potentially prevent GVHD after DLI. Further studies
are required to evaluate the effect of azacitidine early post DLI on GVHD and
GVL.
PMID- 27505706
TI - The etemic model of Gypsy Roma Traveller community vulnerability: is it time to
rethink our understanding of vulnerability?
AB - AIMS AND OBJECTIVES: To present a new etemic model of vulnerability. BACKGROUND:
Despite vulnerability being identified as a core consequence of health and health
experiences, there has been little research exploring the meaning of
vulnerability as a concept. Yet, being vulnerable is known to have dire
physical/mental health consequences. It is therefore a fundamental issue for
nurses to address. To date, the meaning of the term vulnerability has been
influenced by the work of Spiers (Journal of Advanced Nursing, 31, 2000, 715, The
Essential Concepts of Nursing: Building Blocks for Practice, 2005, Elsevier,
London). Spiers identified two aspects of vulnerability: the etic (external
judgment of another persons' vulnerability) and the emic (internal lived
experience of vulnerability). This approach has led to a plethora of research
which has explored the etic (external judgment) of vulnerability and rendered the
internal lived (or emic) experience invisible. Consequences of this, for
marginalised communities such as Gypsy Roma Travellers include a lack of
culturally sensitive services compounding health inequalities. DESIGN: Position
paper. METHOD: Drawing upon a qualitative phenomenological research study
exploring the lived experience of vulnerability from a Gypsy Roma Travelling
community (published previously), this paper presents a new model of
vulnerability. This etemic model of vulnerability values both external and
internal dimensions of vulnerability and argues for a fusion of these two
opposing perspectives. CONCLUSIONS: If nurses and other health- and social care
professionals wish to develop practice that is successful in engaging with Gypsy
Roma Travellers, then there is a need to both understand and respect their
community. This can be achieved through an etemic approach to understanding their
vulnerability achieved by eliciting lived experience alongside the appreciation
of epidemiological studies. RELEVANCE TO CLINICAL PRACTICE: If nurses and health
practitioners used this etemic approach to practice then it would enable both the
development and delivery of culturally sensitive services facilitating health
access to this community. Only then, will their poor health status be
successfully addressed.
PMID- 27505707
TI - Structure Determination of an Ag(I) -Mediated Cytosine-Cytosine Base Pair within
DNA Duplex in Solution with (1) H/(15) N/(109) Ag NMR Spectroscopy.
AB - The structure of an Ag(I) -mediated cytosine-cytosine base pair, C-Ag(I) -C, was
determined with NMR spectroscopy in solution. The observation of 1-bond (15) N
(109) Ag J-coupling ((1) J((15) N,(109) Ag): 83 and 84 Hz) recorded within the C
Ag(I) -C base pair evidenced the N3-Ag(I) -N3 linkage in C-Ag(I) -C. The triplet
resonances of the N4 atoms in C-Ag(I) -C demonstrated that each exocyclic N4 atom
exists as an amino group (-NH2 ), and any isomerization and/or N4-Ag(I) bonding
can be excluded. The 3D structure of Ag(I) -DNA complex determined with NOEs was
classified as a B-form conformation with a notable propeller twist of C-Ag(I) -C
(-18.3+/-3.0 degrees ). The (109) Ag NMR chemical shift of C-Ag(I) -C was
recorded for cytidine/Ag(I) complex (delta((109) Ag): 442 ppm) to completed full
NMR characterization of the metal linkage. The structural interpretation of NMR
data with quantum mechanical calculations corroborated the structure of the C
Ag(I) -C base pair.
PMID- 27505708
TI - Core 2 beta1,6-N-acetylglucosaminyltransferase-I, crucial for P-selectin ligand
expression is controlled by a distal enhancer regulated by STAT4 and T-bet in
CD4+ T helper cells 1.
AB - P-selectin ligands (P-ligs) support the recruitment of lymphocytes into inflamed
tissues. Binding to P-selectin is mediated by oligosaccharide groups synthesized
by means of several glycosyltransferases including core 2 beta1,6-N
acetylglucosaminyltransferase-I (C2GlcNAcT-I), encoded by the gene Gcnt1. Using
Gcnt1(-/-) Th1 cells, we show that C2GlcNAcT-I is crucial for inflammatory T cell
homing in vivo. To understand the molecular regulation of Gcnt1 in CD4(+) T
helper cells, we performed ChIP-on-chip experiments across the Gcnt1 locus
assessing the chromatin structure in P-lig-expressing versus non-expressing
CD4(+) T cells. This identified a distal region about 20kb upstream of the
promoter where the presence of a H3K27me3 mark correlated with Gcnt1 repression.
This region possessed IL-12-dependent enhancer activity in reporter assays, in
accordance with preferential IL-12-dependent induction of Gcnt1 in vitro. STAT4
and T-bet cooperated in control of the enhancer activity. Deficiency in either
one resulted in drastically reduced Gcnt1 mRNA expression in differentiated Th1
cells. While both STAT4 and T-bet were bound to the enhancer early after
activation only T-bet binding persisted throughout the expansion phase after TCR
signal cessation. This suggests sequential action of STAT4 and T-bet at the
enhancer. In summary, we show that Gcnt1 transcription and subsequent P-lig
induction in Th1 cells is governed by binding of STAT4 and T-bet to a distal
enhancer and further regulated by epigenetic marks such as H3K27me3.
PMID- 27505709
TI - Generation and characterization of human B lymphocyte stimulator blocking
monoclonal antibody.
AB - The cytokine, B lymphocyte stimulator (Blys) is essential for activation and
proliferation of B cells and is involved in the pathogenesis of B-cell mediated
autoimmune diseases. Based on its essential activity, Blys may be a potential
therapeutic target for human autoimmune diseases. In this article, we have
described the development of a novel humanized anti-Blys antibody, NMB04, that
binds with high affinity and specificity to both soluble and membrane bound Blys.
This monoclonal antibody has the potential to block Blys binding to all its three
receptors, TACI, BCMA and BR-3. Further in vivo studies revealed that NMB04
possessed more potent inhibitory activity against human Blys as compared to an
existing antibody, Belimumab. Therefore, NMB04 may have potential as a
therapeutic candidate targeting autoimmune diseases.
PMID- 27505710
TI - SIRT1 inhibits inflammatory response partly through regulation of NLRP3
inflammasome in vascular endothelial cells.
AB - Emerging evidence has indicated that vascular endothelial cells (ECs) not only
form the barrier between blood and the vessel wall but also serve as conditional
innate immune cells. Our previous study found that SIRT1, a class III histone
deacetylase, inhibits the inflammatory response in ECs. Recent studies revealed
that SIRT1 also participates in the modulation of immune responses. Although the
NLRP3 inflammasome is known to be a crucial component of the innate immune
system, there is no direct evidence demonstrating the anti-inflammatory effect of
SIRT1 on ECs through the NLRP3 inflammasome. In this study, we observed that
lipopolysaccharide (LPS) and adenosine triphosphate (ATP) triggered the
activation of NLRP3 inflammasome in human umbilical vein ECs (HUVECs). Moreover,
SIRT1 expression was reduced in HUVECs stimulated with LPS and ATP. SIRT1
activator inhibited the expression of monocyte chemotactic protein-1 (MCP-1) and
C-reactive protein (CRP), whereas SIRT1 knockdown resulted in significant
increases in MCP-1 and CRP levels in HUVECs stimulated with LPS and ATP.
Importantly, the lack of SIRT1 enhanced NLRP3 inflammasome activation and
subsequent caspase-1 cleavage. On the other hand, NLRP3 siRNA blocked the
activation of the NLRP3 inflammasome in HUVECs stimulated with LPS plus ATP.
Further study revealed that NLRP3 inflammasome blockade significantly reduced MCP
1 and CRP production in HUVECs. In vivo studies indicated that implantation of
the periarterial carotid collar inhibited arterial SIRT1 expression in rabbits.
Meanwhile, treatment with a SIRT1 activator decreased the expression levels of
MCP-1 and CRP in collared arteries and the interleukin (IL)-1beta level in serum.
Taken together, these findings indicate that NLRP3 inflammasome activation
promoted endothelial inflammation and that SIRT1 inhibits the inflammatory
response partly through regulation of the NLRP3 inflammasome in ECs.
PMID- 27505711
TI - Aire knockdown in medullary thymic epithelial cells affects Aire protein,
deregulates cell adhesion genes and decreases thymocyte interaction.
AB - We demonstrate that even a partial reduction of Aire mRNA levels by siRNA-induced
Aire knockdown (Aire KD) has important consequences to medullary thymic
epithelial cells (mTECs). Aire knockdown is sufficient to reduce Aire protein
levels, impair its nuclear location, and cause an imbalance in large-scale gene
expression, including genes that encode cell adhesion molecules. These genes drew
our attention because adhesion molecules are implicated in the process of mTEC
thymocyte adhesion, which is critical for T cell development and the
establishment of central self-tolerance. Accordingly, we consider the following:
1) mTECs contribute to the elimination of self-reactive thymocytes through
adhesion; 2) Adhesion molecules play a crucial role during physical contact
between these cells; and 3) Aire is an important transcriptional regulator in
mTECs. However, its role in controlling mTEC-thymocyte adhesion remains unclear.
Because Aire controls adhesion molecule genes, we hypothesized that the
disruption of its expression could influence mTEC-thymocyte interaction. To test
this hypothesis, we used a murine Aire(+) mTEC cell line as a model system to
reproduce mTEC-thymocyte adhesion in vitro. Transcriptome analysis of the mTEC
cell line revealed that Aire KD led to the down-modulation of more than 800
genes, including those encoding for proteins involved in cell adhesion, i.e., the
extracellular matrix constituent Lama1, the CAM family adhesion molecules Vcam1
and Icam4, and those that encode peripheral tissue antigens. Thymocytes co
cultured with Aire KD mTECs had a significantly reduced capacity to adhere to
these cells. This finding is the first direct evidence that Aire also plays a
role in controlling mTEC-thymocyte adhesion.
PMID- 27505712
TI - A Lamellar Coordination Polymer with Remarkable Catalytic Activity.
AB - A positively charged lamellar coordination polymer based on a flexible
triphosphonic acid linker is reported. [Gd(H4 nmp)(H2 O)2 ]Cl?2 H2 O (1) [H6
nmp=nitrilotris(methylenephosphonic acid)] was obtained by a one-pot approach by
using water as a green solvent and by forcing the inclusion of additional acid
sites by employing HCl in the synthesis. Compound 1 acts as a versatile
heterogeneous acid catalyst with outstanding activity in organic reactions such
as alcoholysis of styrene oxide, acetalization of benzaldehyde and
cyclohexanaldehyde and ketalization of cyclohexanone. For all reaction systems,
very high conversions were reached (92-97 %) in only 15-30 min under mild
conditions (35 degrees C, atmospheric pressure). The coordination polymer
exhibits a protonic conductivity of 1.23*10(-5) S cm(-1) at 98 % relative
humidity and 40 degrees C.
PMID- 27505713
TI - Flat metallic surface gratings with sub-10 nm gaps controlled by atomic-layer
deposition.
AB - Atomic layer lithography is a recently reported new technology to fabricate deep
subwavelength features down to 1-2 nm, based on combinations of electron beam
lithography (EBL) and atomic layer deposition (ALD). However, the patterning area
is relatively small as limited by EBL, and the fabrication yield is not very high
due to technical challenges. Here we report an improved procedure to fabricate
flat metallic surfaces with sub-10 nm features based on ALD processes. To
demonstrate the scalability of the new manufacturing method, we combine the ALD
process with large area optical interference patterning, which is particularly
promising for the development of practical applications for nanoelectronics and
nanophotonics with extremely strong confinement of electromagnetic fields.
PMID- 27505714
TI - Catalytic Fehling's Reaction: An Efficient Aerobic Oxidation of Aldehyde
Catalyzed by Copper in Water.
AB - The first example of homogeneous copper-catalyzed aerobic oxidation of aldehydes
is reported. This method utilizes atmospheric oxygen as the sole oxidant,
proceeds under extremely mild aqueous conditions, and covers a wide range of
various functionalized aldehydes. Chromatography is generally not necessary for
product purification.
PMID- 27505715
TI - Enterovirus D68 in Critically Ill Children: A Comparison With Pandemic H1N1
Influenza.
AB - OBJECTIVE: In 2014, the Unites States experienced an outbreak of enterovirus D68
associated with severe respiratory illness. The clinical characteristics
associated with severe illness from enterovirus D68 during this outbreak compared
with those associated with the 2009 H1N1 influenza virus outbreak are unknown.
DESIGN AND SETTING: In this retrospective cohort study, we characterized the
clinical features of children with enterovirus D68 admitted to the PICU between
August 1, 2014, and November 1, 2014, and compared them with critically ill
children infected with H1N1 influenza during the pandemic admitted between May 1,
2009, and January 31, 2010. PATIENTS: PICU patients. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Ninety-seven severely ill children with
enterovirus D68 infections were compared with 68 children infected with H1N1
influenza during the 2009 pandemic. Children with enterovirus D68 were more
likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway
disease exacerbations, with greater receipt of albuterol (94% vs 49%) and
steroids (89% vs 40%; p < 0.0001 for both). Although more children with
enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza,
they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower
intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory
distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05
for all). Compared with children with other enteroviruses and rhinoviruses,
children with enterovirus D68 were more likely to have a history of asthma (64%
vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both).
CONCLUSIONS: Critically ill children with enterovirus D68 were more likely to
present with reactive airway disease exacerbations, whereas children with H1N1
influenza were more likely to present with pneumonia. Compared with the pandemic
H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children
requiring admission to the ICU, but was associated with less severe outcomes.
PMID- 27505716
TI - Procedural Sedation Outside of the Operating Room Using Ketamine in 22,645
Children: A Report From the Pediatric Sedation Research Consortium.
AB - OBJECTIVE: Most studies of ketamine administered to children for procedural
sedation are limited to emergency department use. The objective of this study was
to describe the practice of ketamine procedural sedation outside of the operating
room and identify risk factors for adverse events. DESIGN: Observational cohort
review of data prospectively collected from 2007 to 2015 from the multicenter
Pediatric Sedation Research Consortium. SETTING: Sedation services from academic,
community, free-standing children's hospitals and pediatric wards within general
hospitals. PATIENTS: Children from birth to 21 years old or younger.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Describe patient
characteristics, procedure type, and location of administration of ketamine
procedural sedation. Analyze sedation-related adverse events and severe adverse
events. Identify risk factors for adverse events using multivariable logistic
regression. A total of 22,645 sedations performed using ketamine were analyzed.
Median age was 60 months (range, < 1 mo to < 22 yr); 72.0% were American Society
of Anesthesiologists-Physical Status less than III. The majority of sedations
were performed in dedicated sedation or radiology units (64.6%).
Anticholinergics, benzodiazepines, or propofol were coadministered in 19.8%,
57.9%, and 35.4%, respectively. The overall adverse event occurrence rate was
7.26% (95% CI, 6.92-7.60%), and the frequency of severe adverse events was 1.77%
(95% CI, 1.60-1.94%). Procedures were not completed in 39 of 19,747 patients
(0.2%). Three patients experienced cardiac arrest without death, all associated
with laryngospasm. CONCLUSIONS: This is a description of a large prospectively
collected dataset of pediatric ketamine administration predominantly outside of
the operating room. The overall incidence of severe adverse events was low. Risk
factors associated with increased odds of adverse events were as follows: cardiac
and gastrointestinal disease, lower respiratory tract infection, and the
coadministration of propofol and anticholinergics.
PMID- 27505717
TI - Frequency, Composition, and Predictors of In-Transit Critical Events During
Pediatric Critical Care Transport.
AB - OBJECTIVES: Transport of pediatric patients is common due to healthcare
regionalization. We set out to determine the frequency of in-transit critical
events during pediatric critical care transport and identify factors associated
with these events. DESIGN: Retrospective cohort study using administrative and
clinical data. SETTING: Single pediatric critical care transport provider in
Ontario, Canada. PATIENTS: All pediatric care transports between January 1, 2005,
and December 31, 2010. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in
transit critical events, defined by an adaptation of a recent consensus
definition. In-transit critical events occurred in 1,094 (12.3%) of 8,889
transports. Hypotension (3.6%), tachycardia (3.7%), and bradycardia (3.3%) were
the most common critical events. Crews performed medical interventions in 194
transports (2.2%). The frequency and makeup of critical events varied across
patient age groups. Age, pretransport mechanical ventilation, pretransport
cardiovascular instability, transport duration, scene calls, and paramedic crew
level were independently associated with increased risk of in-transit critical
events in multivariate analysis. A Transport Pediatric Early Warning Score of 7
or greater predicted in-transit critical events with high specificity but low
sensitivity (92.0% and 20.0%, respectively), but was not superior of the
combination of pretransport mechanical ventilation and pretransport
cardiovascular instability (sensitivity and specificity of 12.6% and 97.4%,
respectively). Removal of early warning signs from the definition resulted in
critical event rates comparable to those published in adults and improved
predictive performance. CONCLUSIONS: Using new consensus definitions of transport
related critical events, we found critical events occurred in almost one in eight
transports, and were strongly associated with pretransport cardiovascular
instability. Transport Pediatric Early Warning Score was poorly predictive of in
transit critical events, and was not superior to the presence of pretransport
mechanical ventilation and cardiovascular instability. Future prospective studies
are required to elucidate the optimal matching of transport resources to
patients, in particular those with both pretransport cardiovascular instability
and mechanical ventilation.
PMID- 27505718
TI - Concurrent decrease of brain white matter tracts' thicknesses and fractional
anisotropy after antenatal hypoxia-ischemia detected with tract-based spatial
statistics analysis.
AB - PURPOSE: To examine the extent of gray and white matter (WM) injury following
global antenatal hypoxia-ischemia (H-I) and resulting in muscle hypertonia in
newborns in a rabbit cerebral palsy model. MATERIALS AND METHODS: Rabbit dams (n
= 15) underwent uterine ischemia procedure resulting in a global fetal H-I at
embryonic day 22 (embryonic 22 days gestation). Newborn's brains underwent high
resolution diffusion tensor imaging on a 14 Tesla magnet ex vivo. Fractional
anisotropy (FA) in brains of hypertonic (n = 9), nonhypertonic (n = 6), and sham
control (n = 5) kits were compared voxel-wise using Tract-Based Spatial
Statistics (TBSS) approach. Herein, we used a novel method to assess local WM
tracts' thicknesses in TBSS analysis and compare between the groups. RESULTS:
Significant (corrected P < 0.05) reduction of WM FA was found in corpus callosum
splenium (91.2%), periventricular WM (83.5%), fimbria hippocampi (78.8%),
cingulum (81.4%), anterior commissure (95%), internal capsule (83.2%), and optic
tract (82.9%) in the hypertonic group. Significant (corrected P < 0.05) reduction
in WM tracts' thicknesses was found in corpus callosum (73.3%), periventricular
WM (82.5%), cingulum (73.4%), bilaterally in the hypertonic group. CONCLUSION: WM
injury in newborn hypertonic kits 10 days after global fetal H-I is widespread
and involves not only motor but also limbic and commissural fibers in multiple
regions. WM injury in newborn hypertonic kits is manifested by changes in
microstructural properties and decreased FA, as well as reduction of WM volumes,
relative to nonhypertonic kits. J. Magn. Reson. Imaging 2017;45:700-709. LEVEL OF
EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:829-838.
PMID- 27505719
TI - Postpartum hypoglycaemia is common in the immediate postpartum period in Type 1
diabetes.
PMID- 27505720
TI - Andrographolide recovers cognitive impairment in a natural model of Alzheimer's
disease (Octodon degus).
AB - The social species Octodon degus (degu) is the only wild-type South American
rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the
ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane
family obtained from the Asian plant Andrographis paniculata, to recover the
cognitive decline in this long-lived animal model. We administered ANDRO to aged
degus (56-month old) for 3 months. In addition, in 2 control groups (young degus:
12-month old and aged degus: 56-month old), we administrated saline solution as a
vehicle. We evaluated cognitive performance through several behavioral tests. We
also performed a series of physiological and biochemical analyses (e.g.,
electrophysiological and immunoblotting assessment) to identify possible
mechanisms underlying cognitive performance associated with age. Our results
suggest that there is an effect of aging on the loss of cognitive function, and
this decrease in cognitive function was also related to a decrease in the
synaptic functions and an increase in the main hallmarks of Alzheimer's disease
(AD). More importantly, ANDRO treatments showed the following beneficial effects:
(1) recovery of spatial memory and learning performance; (2) recovery of synaptic
basal transmission; (3) partial or complete protection of certain synaptic
proteins; and (4) a specific neuroprotective effect, including the reduction of
phosphorylated tau protein and amyloid beta aggregate maturation in aged degus.
Taken together, our results suggest that ANDRO could be used as a potential
therapy for AD and support the use of O. degus as a natural model in which to
study both neural damage associated with aging processes and the behavioral and
neuropathological hallmarks of aging-related diseases such as AD.
PMID- 27505721
TI - FGF21 Is Not a Major Mediator for Bone Homeostasis or Metabolic Actions of
PPARalpha and PPARgamma Agonists.
AB - Results of prior studies suggest that fibroblast growth factor 21 (FGF21) may be
involved in bone turnover and in the actions of peroxisome proliferator-activated
receptor (PPAR) alpha and gamma in mice. We have conducted independent studies to
examine the effects of FGF21 on bone homeostasis and the role of FGF21 in
PPARalpha and gamma actions. High-fat-diet-induced obesity (DIO) mice were
administered vehicle or recombinant human FGF21 (rhFGF21) intraperitoneally at 0
(vehicle), 0.1, 1, and 3 mg/kg daily for 2 weeks. Additional groups of DIO mice
received water or 10 mg/kg rosiglitazone daily. Mice treated with rhFGF21 or
rosiglitazone showed expected metabolic improvements in glucose, insulin, and
lipid levels. However, bone loss was not detected in rhFGF21-treated mice by dual
energy X-ray absorptiometry (DXA), micro-CT, and histomorphometric analyses.
Mineral apposition rate, a key bone formation parameter, was unchanged by
rhFGF21, while significantly decreased by rosiglitazone in DIO mice. Bone
resorption markers, OPG/RANKL mRNA expression, and histological bone resorption
indices were unchanged by rhFGF21 or rosiglitazone. Bone marrow fat was unchanged
by rhFGF21, while increased by rosiglitazone. Furthermore, FGF21 knockout mice
did not show high bone mass phenotype. Treatment with PPARalpha or PPARgamma
agonists caused similar metabolic effects in FGF21 knockout and wild-type mice.
These results contrast with previous findings and suggest that FGF21 is not
critical for bone homeostasis or actions of PPARalpha and PPARgamma. (c) 2016
American Society for Bone and Mineral Research.
PMID- 27505723
TI - Evaluating the Biological and Ecological Factors Influencing Transmission of
Larval Digenetic Trematodes: A Test of Second Intermediate Host Specificity of
Two North American Halipegus Species.
AB - Host specificity of parasites is a basic principle in parasitology; however, it
is not easily measured. Previously, host specificity was calculated as the number
of species that a parasite infected, but this is not an accurate description of
host usage because some species are capable of being infected but do not
contribute to the completion of the life cycle. Instead, measures of host
specificity should take into consideration interactions between a parasite and a
potential host species as well as interactions between current and subsequent
hosts in the life cycle. The objectives of this study were to track the
development of 2 trematode species, Halipegus eccentricus and Halipegus
occidualis , in 3 phylogenetically and ecologically distinct microcrustacean
second intermediate hosts, and then evaluate the extent to which each of these
hosts contributed to transmission of each Halipegus species to the next odonate
host in the life cycle. All 3 microcrustacean species exposed became infected
with both species of Halipegus. The patterns of growth of H. eccentricus and H.
occidualis were similar, but there were consistent differences in the rates of
growth among the microcrustacean species in both Halipegus species. Regardless of
host species infected, all individuals of both species were considered to be
developmentally infective to the next host in the life cycle by 19 days
postexposure (DPE) when they lost their excretory bladder. Worms of varying sizes
were capable of surviving without this structure, suggesting that there is not a
strong relationship between the rate of growth of the metacercariae and the
development of their osmoregulatory system. Although Halipegus species were
capable of living without an excretory bladder at 19 DPE, there were differences
in their size and rates at which the 3 microcrustaceans contributed to
transmission of the parasites to subsequent odonate hosts. Collectively, under
controlled laboratory conditions, there was an approximate 2-fold difference in
the average percentage of worms that established in odonates from the ostracod,
Cypridopsis sp., than from the harpacticoid copepod, Phyllognathopus sp., and the
difference was nearly 3-fold between Cypridopsis sp. and the cyclopoid copepod,
Thermocyclops sp. Therefore, despite all 3 microcrustacean species becoming
infected, not all species were equally suited for transmission and completion of
the life cycle. Differences among the 3 microcrustacean species in cercaria
ingestion, metacercarial growth and development, and odonate predation rates on
infected microcrustacean species were important factors in determining
transmission of the 2 Halipegus species to odonate hosts.
PMID- 27505724
TI - Diagnostic accuracy of Japanese posttraumatic stress measures after a complex
disaster: The Fukushima Health Management Survey.
AB - BACKGROUND: The Posttraumatic Stress Disorder (PTSD) Checklist (PCL) has been
widely used among traumatized populations to screen people with PTSD; however,
the Japanese version of the PCL has yet to be validated. We examined the
diagnostic accuracy of the Japanese version PCL-Specific (PCL-S) and the
abbreviated versions of the PCL-S among the evacuees of the Fukushima Daiichi
Nuclear Power Plant accident. METHODS: Fifty-one participants were recruited from
an evacuee and clinical sample. The PCL-S, Impact of Event Scale-Revised (IES-R),
and World Health Organization Composite International Diagnostic Interview were
administered. Screening properties of the PCL-S, IES-R, and abbreviated PCL-S
against PTSD diagnosis, including sensitivity, specificity, and diagnostic
efficiency, were calculated. Receiver operating characteristic curves were drawn,
and optimal cutoff points were examined. RESULTS: The sensitivity, specificity,
and diagnostic efficiency of the PCL-S were 66.7%, 84.9%, and 79.2%, respectively
(at 52, the area under the curve was 0.83). The cutoff point method for the PCL-S
performed better than did the symptom cluster method. The screening properties of
the abbreviated versions were comparable with those of the full version.
CONCLUSIONS: The Japanese version of the PCL-S showed moderate diagnostic
accuracy and improved performance over the IES-R for PTSD diagnosis based on the
Diagnostic and Statistical Manual of Mental Disorders, fourth edition. The
Japanese version of the PCL-S was a reliable and valid measure, and its
diagnostic accuracy was reasonable for both full and abbreviated versions.
PMID- 27505725
TI - Boosted photocatalytic efficiency through plasmonic field confinement with bowtie
and diabolo nanostructures under LED irradiation.
AB - Photoresist and electron beam lithography techniques were used to fabricate
embedded Ag bowtie and diabolo nanostructures with various apex angles on the
surface of a TiO2 film. The reinforced localized surface plasmon
resonance (LSPR) and electric field generated at both the Ag/TiO2 and
air/TiO2 interfaces enabled high light absorbance in the
TiO2 nanostructure. Results for both the bowtie and diabolo
nanostructures showed that a reduction in the apex angle enhances both LSPR and
Raman intensity. The maximum electric current density observed at the apex
indicates that the strongest SPR confines at the tip gap of the bowtie and
corners of the diabolo. In a long-wavelength region, as the apex angle increases,
the resonant peak wavelength of the standing wave matches the increased length of
the prism edges of the bowtie and diabolo to create a redshift. In a short
wavelength region, as the apex angle increases, the blueshift of the resonant
peak wavelength is presumably attributable to the increase in the effective index
of the local surface plasmon polariton standing wave mainly residing along both
the bowtie and diabolo axes. The redshift and blueshift trend in the simulation
results for the resonant peak wavelength agrees well with the experimental
results. The fastest photocatalytic rate was obtained by placing the
Ag/TiO2 bowtie at an apex angle of 30 degrees in the methylene blue
solution, revealing that the plasmonic photocatalysis causes the highest
degradation efficiency. This is because the Schottky junction and LSPR can
stimulate many valid radicals for the environmental improvement.
PMID- 27505726
TI - Manganese-doped near-infrared emitting nanocrystals for in vivo biomedical
imaging.
AB - Nanoprobes with multiple imaging modality have attracted a great deal of
attention due to the capability of offering complementary information from each
individual component. This work presents a hybrid approach to synthesize
manganese doped near infrared (NIR) emitting quantum dots. The Mn-doping process
was accomplished in aqueous phase followed by a phase transfer to organic phase
for ZnS coating. This bimodal nanoprobe displayed high NIR luminescence quantum
yield (~14%) and capability of magnetic resonance imaging (MRI) (1.44 mM
1 s-1). The RGD-targeted nanoprobes have been exploited for in
vitro cell labelling, in vivo tumor targeting and lymph node mapping. In
addition, no adverse toxic effects were observed, demonstrating the high
biocompatibility of this nanoprobe.
PMID- 27505727
TI - Tensile-strained Ge/SiGe quantum-well photodetectors on silicon substrates with
extended infrared response.
AB - We report on tensile-strained Ge/Si0.11Ge0.89 quantum-well
(QW) metal-semiconductor-metal (MSM) photodetectors on Si substrates. A tensile
strain of 0.21% is introduced into the Ge wells by growing the QW stack on in
situ annealed Ge-on-Si virtual substrates (VS). The optical characterization of
Ge/Si0.11Ge0.89 QW MSM photodetectors indicates that the
optical response increases to a wavelength of 1.5 MUm or higher owing to the
strain-induced direct bandgap shrinkage. Analysis of the band structure by using
a k . p model suggests that by optimizing the tensile strain and Ge well width,
tensile-strained Ge/SiGe QW photodetectors can be designed to cover the
telecommunication C-band and beyond for optical telecommunications and on-chip
interconnection.
PMID- 27505728
TI - Ultrafast pump-probe ellipsometry setup for the measurement of transient optical
properties during laser ablation.
AB - Ultrashort pulsed lasers offer a high potential in precise and efficient material
processing and deep understanding of the fundamental laser-material interaction
aspects is of great importance. The transient pulse reflectivity in conjunction
with the transient absorption influences decisively the laser-material
interaction. Direct measurements of the absorption properties by ultrafast time
resolved ellipsometry are missing to date. In this work, a unique pump-probe
ellipsometry microscope is presented allowing the determination of the transient
complex refractive index with a sub-ps temporal resolution. Measurements on
molybdenum show ultrafast optical penetration depth changes of -6% to + 77%
already within the first 10 ps after the laser pulse impact. This indicates a
significant absorption variation of the pump pulse or subsequent pulses
irradiating the sample on this timescale and paves the road towards a better
understanding of pulse duration dependent laser ablation efficiency, double or
burst mode laser ablation and lattice modifications in the first ps after the
laser pulse impact.
PMID- 27505729
TI - Electrically controllable plasmonic enhanced coherent random lasing from dye
doped nematic liquid crystals containing Au nanoparticles.
AB - An electrically controllable plasmonic enhanced coherent random lasing from the
dye-doped nematic liquid crystal containing Au nanoparticles is demonstrated. To
achieve the optimal control of the RL properties, the polarization of the pump
light should be parallel to the rubbing direction of the cells. The lasing output
intensity is direction-dependent and the substantial output distributes in an
angle range of 0 degrees ~30 degrees deviating from the direction of the pump
stripe. The coherent feedback associated with the coherent random lasing mainly
originates from the cooperative effect of the enhanced localized electric field
in the vicinity of Au nanoparticles and the multiple scattering caused by the
fluctuations of the liquid crystal director and local dielectric tensor.
PMID- 27505730
TI - Acentric langanite La3Ga5.5Nb0.5O14
crystal: a new nonlinear crystal for the generation of mid-infrared parametric
light.
AB - The mid-infrared spectral range extending from 2 to 6 MUm is significant for
scientific and technological applications. A promising nonlinear oxide crystal
La3Ga5.5Nb0.5O14 (LGN) is proposed
and fully characterized for the first time to our knowledge. The transparency
range extends between 0.28 and 7.4 MUm. The two principal refractive indices were
measured and we found that the nonlinear coefficient d11 = 3.0 +/- 0.1 pm/V at
0.532 MUm. The simultaneous fit of data allowed us to refine the Sellmeier
equations of LGN and to calculate the tuning curves for optical parametric
generation (OPG) pumped at 1.064 MUm. Calculations are consistent with recorded
data and also show the generation of a supercontinuum between 1.5 and 3.5 MUm
when pumped at 0.98 MUm by a Ti:Sapphire laser.
PMID- 27505731
TI - Laser damage mechanisms in conductive widegap semiconductor films.
AB - Laser damage mechanisms of two conductive wide-bandgap semiconductor films -
indium tin oxide (ITO) and silicon doped GaN (Si:GaN) were studied via
microscopy, spectroscopy, photoluminescence (PL), and elemental analysis.
Nanosecond laser pulse exposures with a laser photon energy (1.03 eV, 1064 nm)
smaller than the conductive films bandgaps were applied and radically different
film damage morphologies were produced. The laser damaged ITO film exhibited
deterministic features of thermal degradation. In contrast, laser damage in the
Si:GaN film resulted in highly localized eruptions originating at interfaces. For
ITO, thermally driven damage was related to free carrier absorption and, for GaN,
carbon complexes were proposed as potential damage precursors or markers.
PMID- 27505732
TI - Magneto-optical Q-switching using magnetic garnet film with micromagnetic
domains.
AB - High-power giant pulses can be used applied in various applications with Q
switched micro-lasers. This method can shorten the pulse duration; however,
active control is currently impossible in micro-lasers. To achieve precise pulse
control while maintaining compactness and simplicity, we exploit the magneto
optical effect in magnetic garnet films with micromagnetic domains that can be
actively controlled by a pulsed magnetic field. Our Q-switching technique
enhances the output power by a factor of 4 * 103. Moreover, the device
itself is smaller than other Q-switching devices. This novel type of active Q
switch can be combined with a micro-laser to obtain megawatt-order pulses.
PMID- 27505733
TI - Large area compatible broadband superabsorber surfaces in the VIS-NIR spectrum
utilizing metal-insulator-metal stack and plasmonic nanoparticles.
AB - Plasmonically enhanced absorbing structures have been emerging as strong
candidates for photovoltaic (PV) devices. We investigate metal-insulator-metal
(MIM) structures that are suitable for tuning spectral absorption properties by
modifying layer thicknesses. We have utilized gold and silver nanoparticles to
form the top metal (M) region, obtained by dewetting process compatible with
large area processes. For the middle (I) and bottom (M) layers, different
dielectric materials and metals are investigated. Optimum MIM designs are
discussed. We experimentally demonstrate less than 10 percent reflection for most
of the visible (VIS) and near infrared (NIR) spectrum. In such stacks,
computational analysis shows that the bottom metal is responsible for large
portion of absorption with a peak of 80 percent at 1000 nm wavelength for
chromium case.
PMID- 27505734
TI - Remote beating of parallel or orthogonally polarized dual-wavelength optical
carriers for 5G millimeter-wave radio-over-fiber link.
AB - A novel millimeter-wave radio over fiber (MMW-RoF) link at carrier frequency of
35-GHz is proposed with the use of remotely beating MMW generation from reference
master and injected slave colorless laser diode (LD) carriers at orthogonally
polarized dual-wavelength injection-locking. The slave colorless LD supports
lasing one of the dual-wavelength master modes with orthogonal polarizations,
which facilitates the single-mode direct modulation of the quadrature amplitude
modulation (QAM) orthogonal frequency division multiplexing (OFDM) data. Such an
injected single-carrier encoding and coupled dual-carrier transmission with
orthogonal polarization effectively suppresses the cross-heterodyne mode-beating
intensity noise, the nonlinear modulation (NLM) and four-wave mixing (FWM)
sidemodes during injection locking and fiber transmission. In 25-km single-mode
fiber (SMF) based wireline system, the dual-carrier under single-mode encoding
provides baseband 24-Gbit/s 64-QAM OFDM transmission with an error vector
magnitude (EVM) of 8.8%, a bit error rate (BER) of 3.7 * 10-3, a power
penalty of <1.5 dB. After remotely self-beating for wireless transmission, the
beat MMW carrier at 35 GHz can deliver the passband 16-QAM OFDM at 4 Gbit/s to
show corresponding EVM and BER of 15.5% and 1.4 * 10-3, respectively,
after 25-km SMF and 1.6-m free-space transmission.
PMID- 27505735
TI - Ultra-compact strain- and temperature-insensitive torsion sensor based on a line
by-line inscribed phase-shifted FBG.
AB - A novel temperature- and strain-independent optical fiber torsion sensor based on
a phase-shifted fiber Bragg grating (PSFBG) inscribed by the line-by-line (LbL)
technique in a standard single-mode fiber with a femtosecond laser has been
proposed and experimentally demonstrated. The strong birefringence created by the
LbL inscription technique leads to the significant polarization splitting of the
transmission peak of the PSFBG. By simply monitoring the variation of the
amplitude difference between the two polarization-peaks, the fiber torsion angle
and the fiber torsion direction can be simultaneously deduced without temperature
and strain confusion. The torsion sensor exhibits a high torsion sensitivity of
up to -1032.71 dB/(rad/mm), with the distinct advantages of low manufacture cost,
small dimension (just ~1.72mm), and extremely robust and simple structure, which
make it very attractive for practical applications. To the best of our knowledge,
this is the smallest torsion sensor ever reported.
PMID- 27505736
TI - Sensitivity optimization with cladding-etched long period fiber gratings at the
dispersion turning point.
AB - This work presents a refractive index sensor based on a long period fiber grating
(LPFG) made in a reduced cladding fiber whose low order cladding modes have the
turning point at large wavelengths. The combination of these parameters results
in an improved sensitivity of 8734 nm/refractive index unit (RIU) for the
LP0,3 mode in the 1400-1650 wavelength range. This value is similar to
that obtained with thin-film coated LPFGs, which permits to avoid the coating
deposition step. The numerical simulations are in agreement with the experimental
results.
PMID- 27505737
TI - Novel 3D measurement system based on speckle and fringe pattern projection.
AB - An efficient three-dimensional shape measurement system is proposed, which is
based on the combining projection of single digital speckle pattern and phase
shifting fringe patterns. At the beginning, the initial corresponding point for
each pixel is obtained by a novel speckle-phase combination method. The initial
information can be calculated by the single speckle pattern in a short time,
while the phase information is used to ensure the results. Unlike the
conventional methods, it is not necessary to obtain the unwrapped phase,
therefore the number of projected patterns is reduced greatly. Then accurate
corresponding coordinates are obtained according to the wrapped phase. Three
cases are analyzed while adjusting the initial corresponding coordinates locally.
Thus accuracy coordinates are obtained without missing or incorrect points.
Experiments demonstrate that we can achieve accurate reconstruction results with
reduced measurement time by the proposed method.
PMID- 27505738
TI - Depth position recognition-related laser-induced damage test method based on
initial transient damage features.
AB - Even absorptive defects or inner cracks hiding several micrometers to a few dozen
micrometers beneath the top surface can induce damage to transmission elements in
the ultraviolet band. The extremely small size and disordered state of such
defects or cracks hinder their detection using conventional methods. Therefore,
the diagnosis of factors that limit damage resistance performance is a key
technique for improving the fabrication technology of optical elements. With a
focus on laser damage to third-harmonic transmission elements, this study
establishes a micron space-resolved and nanosecond time-resolved imaging system
on the basis of the pump-probe detection technique. The changes in the properties
of defect-induced laser damage in the time domain are clarified. A diagnostic
method for original damage depth in micron precision is proposed according to
damage behaviors. This method can retrieve initial information on damage
inducement and depth position. The recognition and diagnostic capabilities of
such a technique are calibrated with artificial samples and then used to analyze
real samples.
PMID- 27505739
TI - Performance of GaN-on-Si-based vertical light-emitting diodes using silicon
nitride electrodes with conducting filaments: correlation between filament
density and device reliability.
AB - Transparent conductive electrodes with good conductivity and optical
transmittance are an essential element for highly efficient light-emitting
diodes. However, conventional indium tin oxide and its alternative transparent
conductive electrodes have some trouble with a trade-off between electrical
conductivity and optical transmittance, thus limiting their practical
applications. Here, we present silicon nitride transparent conductive electrodes
with conducting filaments embedded using the electrical breakdown process and
investigate the dependence of the conducting filament density formed in the
transparent conductive electrode on the device performance of gallium nitride
based vertical light-emitting diodes. Three gallium nitride-on-silicon-based
vertical light-emitting diodes using silicon nitride transparent conductive
electrodes with high, medium, and low conducting filament densities were prepared
with a reference vertical light-emitting diode using metal electrodes. This was
carried to determine the optimal density of the conducting filaments in the
proposed silicon nitride transparent conductive electrodes. In comparison, the
vertical light-emitting diodes with a medium conducting filament density
exhibited the lowest optical loss, direct ohmic behavior, and the best current
injection and distribution over the entire n-type gallium nitride surface,
leading to highly reliable light-emitting diode performance.
PMID- 27505740
TI - Bidirectional current triggering in planar devices based on serially connected
VO2 thin films using 965 nm laser diode.
AB - By incorporating a 965 nm laser diode, the bidirectional current triggering of up
to 30 mA was demonstrated in a two-terminal planar device based on serially
connected vanadium dioxide (VO2) thin films grown by pulsed laser
deposition. The bidirectional current triggering was realized by using the
focused beams of laser pulses through the photo-thermally induced phase
transition of VO2. The transient responses of laser-triggered currents
were also investigated when laser pulses excited the device at a variety of pulse
widths and repetition rates of up to 4.0 Hz. A switching contrast between off-
and on-state currents was obtained as ~8333, and rising and falling times were
measured as ~39 and ~29 ms, respectively, for 50 ms laser pulses.
PMID- 27505741
TI - Surface plasmon optical antennae in the infrared region with high resonant
efficiency and frequency selectivity.
AB - Infrared light has received attention for sensor applications, including
fingerprint spectroscopy, in the bioengineering and security fields. Surface
plasmon physics enables the operation of a light harvesting optical antenna. Gold
nanochains exhibit localized surface plasmon resonance (LSPR) in the infrared
region with high frequency selectivity. However, a feasible design for optical
antennae with a higher resonant efficiency and frequency selectivity as a
function of structural design and periodicity is still unknown. In the present
study, we investigated the relationship between the resonant efficiency and
frequency selectivity as a function of the structural design of gold nanochains
and explored structural periodicity for obtaining highly frequency-selective
optical antennae. An optical antenna design with higher resonant efficiency is
proposed on the basis of its efficient interaction with non-polarized light.
PMID- 27505742
TI - All-dielectric circular polarizer with nearly unit transmission efficiency based
on cascaded tensor Huygens surface.
AB - In this paper, we demonstrate a high-efficiency and broadband circular polarizer
based on cascaded tensor Huygens surface capable of operating in the near
infrared region. The high efficiency originates from the simultaneous excitation
of the Mie-type electric and magnetic dipole resonances within an all-dielectric
rotationally twisted strips array. Due to the symmetry breaking of the structure
in the light propagation, one state of the circularly polarized light can pass
through freely, while the other state is largely blocked. The maximum
polarization transmission reaches 0.97 with a polarization suppression ratio of
911:1, which represents a major advance in the performance compared with
previously reported circular polarizers. The proposed metamaterial possessing the
merits of high efficiency and simple inclusions has potentials for applications
in biological detector, optical communication and sensor.
PMID- 27505743
TI - Polarization volume grating with high efficiency and large diffraction angle.
AB - We propose a polarization volume grating (PVG), which exhibits nearly 100%
diffraction efficiency and large diffraction angle. Both reflective and
transmissive PVGs can be configured depending on application preference. Such a
PVG is polarization-sensitive so that it can split an incident unpolarized beam
into two well-separated yet polarized beams. These outstanding features make PVG
a strong candidate for photonic and display applications. To investigate and
optimize the diffraction properties, we build a rigorous simulation model based
on finite element method. To illustrate its potential applications, we propose a
simple 2D/3D wearable display using a planar waveguide comprising of two
reflective PVGs.
PMID- 27505744
TI - Broadband gold nanoantennas arrays with transverse dimension effects.
AB - Broadband resonance in gold paired-rods nanoantennas and paired-strips gratings
is investigated when the nanostructure's transverse (non-polarization) dimension
is changed from paired-rods to paired-strips. Increasing the transverse dimension
blue shifts the resonance wavelength and widens its bandwidth due to cancellation
of the magnetic field between nanoantennas. A derived resistor-inductor-capacitor
(RLC) equivalent circuit model verifies the nanostructures' resonance when
elongating the transverse dimensions. Paired-strips gratings have a bandwidth
2.04 times that of paired-rods nanoantennas.
PMID- 27505745
TI - Effects of losses in the atom-light hybrid SU(1,1) interferometer.
AB - Collective atomic excitation can be realized by the Raman scattering. Such a
photon-atom interface can form an SU(1,1)-typed atom-light hybrid interferometer,
where the atomic Raman amplification processes take the place of the beam
splitting elements in a traditional Mach-Zehnder interferometer. We numerically
calculate the phase sensitivities and the signal-to-noise ratios (SNRs) of this
interferometer with the method of homodyne detection and intensity detection, and
give their differences of the optimal phase points to realize the best phase
sensitivities and the maximal SNRs from these two detection methods. The
difference of the effects of loss of light field and atomic decoherence on
measure precision is analyzed.
PMID- 27505746
TI - Random sources for cusped beams.
AB - We introduce two novel classes of partially coherent sources whose degrees of
coherence are described by the rectangular Lorentz-correlated Schell-model (LSM)
and rectangular fractional multi-Gaussian-correlated Schell-model (FMGSM)
functions. Based on the generalized Collins formula, analytical expressions are
derived for the spectral density distributions of these beams propagating through
a stigmatic ABCD optical system. It is shown that beams belonging to both classes
form the spectral density apex that is much higher and sharper than that
generated by the Gaussian Schell-model (GSM) beam with a comparable coherence
state. We experimentally generate these beams by using a nematic, transmissive
spatial light modulator (SLM) that serves as a random phase screen controlled by
a computer. The experimental data is consistent with theoretical predictions.
Moreover, it is illustrated that the FMGSM beam generated in our experiments has
a better focusing capacity than the GSM beam with the same coherence state. The
applications that can potentially benefit from the use of novel beams range from
material surface processing, to communications and sensing through random media.
PMID- 27505747
TI - Excitation powder dependent optical temperature behavior of Er3+ doped
transparent Sr0.69La0.31F2.31 glass ceramics.
AB - The knowledge of the pump power for which the population of thermally coupled
energy levels (TCL) changes with power increase is of valuable importance for
optical temperature sensors. In this paper, novel Er3+ doped
transparent Sr0.69La0.31F2.31 glass ceramics was
fabricated successfully, and its structure is studied by XRD, TEM and HRTEM
analyses. The 2H11/2/4S3/2,
4F9/2(1)/4F9/2(2), and
4I9/2(1)/4I9/2(2) levels of
Er3+ are proved as TCL by analyzing the temperature dependent
fluorescence intensity ratios. The spectrum split, thermal quenching ratio,
population stability, and temperature sensitivity from three TCL are observed to
be dependent on the pump power. A new fitting method has been developed to
establish the relation between fluorescence intensity ratios and temperature. It
is found that the combined use of
2H11/2/4S3/2 and
4F9/2(1)/4F9/2(2) as thermally
coupled energy levels will get a more precise temperature reading from 62.7 K to
800 K with the help of low excitation power at 66.8 mW/mm2.
PMID- 27505748
TI - Analytical surrogate model for the aberrations of an arbitrary GRIN lens.
AB - Current analytical expressions between Gradient-Index (GRIN) lens parameters and
optical aberrations are limited to paraxial approximations, which are not
suitable for realizing GRIN lenses with wide fields of view or small f-numbers.
Here, an analytical surrogate model of an arbitrary GRIN lens ray-trace
evaluation is formulated using multivariate polynomial regressions to correlate
input GRIN lens parameters with output Zernike coefficients, without the need for
approximations. The time needed to compute the resulting surrogate model is over
one order-of-magnitude faster than traditional ray trace simulations with very
little losses in accuracy, which can enable previously infeasible design studies
to be completed.
PMID- 27505749
TI - High-voltage integrated active quenching circuit for single photon count rate up
to 80 Mcounts/s.
AB - Single photon avalanche diodes (SPADs) have been subject to a fast improvement in
recent years. In particular, custom technologies specifically developed to
fabricate SPAD devices give the designer the freedom to pursue the best detector
performance required by applications. A significant breakthrough in this field is
represented by the recent introduction of a red enhanced SPAD (RE-SPAD)
technology, capable of attaining a good photon detection efficiency in the near
infrared range (e.g. 40% at a wavelength of 800 nm) while maintaining a
remarkable timing resolution of about 100ps full width at half maximum. Being
planar, the RE-SPAD custom technology opened the way to the development of SPAD
arrays particularly suited for demanding applications in the field of life
sciences. However, to achieve such excellent performance custom SPAD detectors
must be operated with an external active quenching circuit (AQC) designed on
purpose. Next steps toward the development of compact and practical multichannel
systems will require a new generation of monolithically integrated AQC arrays. In
this paper we present a new, fully integrated AQC fabricated in a high-voltage
0.18 um CMOS technology able to provide quenching pulses up to 50 Volts with fast
leading and trailing edges. Although specifically designed for optimal operation
of RE-SPAD devices, the new AQC is quite versatile: it can be used with any SPAD
detector, regardless its fabrication technology, reaching remarkable count rates
up to 80 Mcounts/s and generating a photon detection pulse with a timing jitter
as low as 119 ps full width at half maximum. The compact design of our circuit
has been specifically laid out to make this IC a suitable building block for
monolithically integrated AQC arrays.
PMID- 27505750
TI - Spectroscopic and laser characterization of
Yb0.15:(LuxY1
x)3Al5O12 ceramics with different Lu/Y
balance.
AB - We report a broad comparative analysis of the spectroscopic and laser properties
of solid solution Lutetium-Yttrium Aluminum Garnet (LuYAG, (LuxY1
x)3Al5O12) ceramics doped with Yb. The
investigation was mainly aimed to assess the impact of the Lu/Y ratio on the Yb
optical and laser properties. Therefore we analyzed a set of samples with
different Y/Lu balance, namely 25/75, 50/50 and 75/25, with 15% Yb doping. We
found that the Yb absorption and emission spectra changed from YAG to LuAG when
gradually increasing in Lu content. Regarding the laser emission, remarkable
results were achieved with all samples. Maximum output power was 8.2 W, 7.3 W and
8.7 W for Y/Lu balance 25/75, 50/50 and 75/25 respectively, at 1030 nm; the slope
efficiency and the optical-to-optical efficiencies approached or exceeded 60% and
50% respectively. The tuning range was investigated using an intracavity ZnSe
prism. The broadest tuning range (998 nm to 1063 nm) was obtained with Y/Lu
balance 75/25, whereas the emission of the other two samples extended from 1000
nm to 1058 nm. To the best of our knowledge, this is the first comparative
analysis of Yb:LuYAG ceramics or crystals as laser host across such a broad range
of Y/Lu ratios.
PMID- 27505751
TI - Broadband OPCPA system with 11 mJ output at 1 kHz, compressible to 12 fs.
AB - We report on a broadband OPCPA system, pumped at 515 nm by frequency doubled
Yb:YAG thin disk lasers. The system delivers 11.3 mJ pulses at a central
wavelength of 800 nm with a spatial beam quality of M2 = 1.25 and >
25% pump-to-signal conversion efficiency. The broadband pulses were demonstrated
to be compressible to 12 fs using a chirped mirror compressor.
PMID- 27505752
TI - Near perfect mode overlap between independently seeded, gain-switched lasers.
AB - We drastically improve the mode overlap between independently seeded, gain
switched laser diodes operating at gigahertz repetition rates by implementing a
pulsed light seeding technique. Injecting pulsed light reduces the emission time
jitter and enables frequency chirp synchronization while maintaining random
optical phases of the emitted laser pulses. We measure interference of these
pulsed sources both in the macroscopic regime, where we demonstrate near perfect
mode overlap, and in the single photon regime, where we achieve a Hong-Ou-Mandel
dip visibility of 0.499 +/- 0.004, thus saturating the theoretical limit of 0.5.
The measurement results are reproduced by Monte-Carlo simulations with no free
parameters. Our light source is an ideal solution for generation of high rate,
indistinguishable coherent pulses for quantum information applications.
PMID- 27505753
TI - Third harmonic generation in exposed-core microstructured optical fibers.
AB - Inter-modal phase-matched third harmonic generation has been demonstrated in an
exposed-core microstructured optical fiber. Our fiber, with a partially open core
having a diameter of just 1.85 um, shows efficient multi-peak third-harmonic
generation between 500 nm and 530 nm, with a maximum visible-wavelength output of
0.96 MUW. Mode images and simulations show strong agreement, confirming the phase
matching process and polarization dependence. We anticipate this work will lead
to tailorable and tunable visible light sources by exploiting the open access to
the optical fiber core, such as depositing thin-film coatings in order to shift
the phase matching conditions.
PMID- 27505754
TI - High luminous efficacy green light-emitting diodes with AlGaN cap layer.
AB - We demonstrate very high luminous efficacy green light-emitting diodes employing
Al0.30Ga0.70N cap layer grown on patterned sapphire
substrates by metal organic chemical vapor deposition. The peak external quantum
efficiency and luminous efficacies were 44.3% and 239 lm/w, respectively. At 20
mA (20 A/cm2) the light output power was 14.3 mW, the forward voltage
was 3.5 V, the emission wavelength was 526.6 nm, and the external quantum
efficiency was 30.2%. These results are among the highest reported luminous
efficacy values for InGaN based green light-emitting diodes.
PMID- 27505755
TI - Optical antennas with sinusoidal modulation in width.
AB - Small metal structures sustaining plasmon resonances in the optical regime are of
great interest due to their large scattering cross sections and ability to
concentrate light to subwavelength volumes. In this paper, we study the dipolar
plasmon resonances of optical antennas with a constant volume and a sinusoidal
modulation in width. We experimentally show that by changing the phase of the
width-modulation, with a small 10 nm modulation amplitude, the resonance shifts
over 160 nm. Using simulations we show how this simple design can create
resonance shifts greater than 600 nm. The versatility of this design is further
shown by creating asymmetric structures with two different modulation amplitudes,
which we experimentally and numerically show to give rise to two resonances. Our
results on both the symmetric and asymmetric antennas show the capability to
control the localization of the fields outside the antenna, while still
maintaining the freedom to change the antenna resonance wavelength. The antenna
design we tested combines a large spectral tunability with a small footprint: all
the antenna dimensions are factor 7 to 13 smaller than the wavelength, and hold
potential as a design element in meta-surfaces for beam shaping.
PMID- 27505756
TI - Dynamically tunable plasmonically induced transparency in sinusoidally curved and
planar graphene layers.
AB - To achieve plasmonically induced transparency (PIT), general near-field plasmonic
systems based on couplings between localized plasmon resonances of nanostructures
rely heavily on the well-designed interantenna separations. However, the
implementation of such devices and techniques encounters great difficulties
mainly to due to very small sized dimensions of the nanostructures and gaps
between them. Here, we propose and numerically demonstrate that PIT can be
achieved by using two graphene layers that are composed of a upper sinusoidally
curved layer and a lower planar layer, avoiding any pattern of the graphene
sheets. Both the analytical fitting and the Akaike Information Criterion (AIC)
method are employed efficiently to distinguish the induced window, which is found
to be more likely caused by Autler-Townes splitting (ATS) instead of
electromagnetically induced transparency (EIT). Besides, our results show that
the resonant modes cannot only be tuned dramatically by geometrically changing
the grating amplitude and the interlayer spacing, but also by dynamically varying
the Fermi energy of the graphene sheets. Potential applications of the proposed
system could be expected on various photonic functional devices, including
optical switches, plasmonic sensors.
PMID- 27505757
TI - Electrical and optical performance of plasmonic silicon solar cells based on
light scattering of silver and indium nanoparticles in matrix-combination.
AB - This study demonstrates the efficacy of combining a matrix of silver
nanoparticles (Ag-NPs) with indium nanoparticles (In-NPs) to improve the electric
and optical performance of plasmonic silicon solar cells. We examined the
excitation of localized surface plasmons of Ag-NPs and In-NPs using surface
enhanced Raman scattering measurements. Optical reflectance and external quantum
efficiency (EQE) measurements demonstrate that the light scattering of Ag-NPs at
short wavelengths can be improved by surrounding them with In-NPs. This also
leads to high EQE band matching in the high energy band of the AM1.5G solar
energy spectrum. Impressive improvements in optical reflectance and EQE response
were also observed at short wavelengths. Cells with a matrix of Ag-NPs (20%
surface coverage) surrounded by In-NPs (80% surface coverage) increased the
overall efficiency of the cell by 31.83%, as confirmed by photovoltaic current
density-voltage characterization under AM 1.5 G illumination.
PMID- 27505758
TI - Enhance the light-harvesting capability of the ITO-free inverted small molecule
solar cell by ZnO nanorods.
AB - The ITO-free inverted SMPV1:PC71BM solar cells with an Al doped ZnO
(AZO) transparent electrodes are fabricated. The AZO thin film prepared by pulsed
laser deposition (PLD) technique exhibits high transmission (>85%) and low sheet
resistance (~30 Omega/sq) and the power conversion efficiency (PCE) of devices
based on AZO electrode can reach around 4%. To further enhance the light
harvesting of the absorption layer of solar cells, ZnO nanorods interlayer is
grown on the AZO layer before the deposition the active layer. The absorption
spectrums of devices under various conditions are also simulated by RCWA method
to identify the optical saturation length of the ZnO nanorods. The PCE of ITO
free inverted small molecule solar cell improved with ZnO nanorods can reach
6.6%.
PMID- 27505759
TI - Large spontaneous-emission enhancements in metallic nanostructures: towards LEDs
faster than lasers.
AB - Recent progress in the design and realization of optical antennas enclosing
fluorescent materials has demonstrated large spontaneous-emission enhancements
and, simultaneously, high radiation efficiencies. We discuss here that an
important objective of such work is to increase spontaneous-emission rates to
such a degree that light-emitting diodes (LEDs) can possess modulation speeds
exceeding those of typical semiconductor lasers, which are usually in the range
~20-50 GHz. We outline the underlying physics that enable large spontaneous
emission enhancements in metallic nanostructures, and we then discuss recent
theoretical and experimentally promising results, where enhancements larger than
a factor of ~300 have been reported, with radiation efficiencies exceeding 50%.
We provide key comparative advantages of these structures in comparison to
conventional dielectric microcavity designs, namely the fact that the enhancement
of spontaneous emission can be relatively nonresonant (i.e., broadband) and that
the antenna nanostructures can be spectrally and structurally compatible for
integration with a wide class of emitters, including organic dyes, diamond
nanocrystals and colloidal quantum dots. Finally, we point out that physical
insight into the underlying effects can be gained by analyzing these metallic
nanostructures in their equivalent-circuit (or nano-antenna) model, showing that
all main effects (including the Purcell factor) can adequately be described in
that approach.
PMID- 27505760
TI - Estimating index of refraction from polarimetric hyperspectral imaging
measurements.
AB - Current material identification techniques rely on estimating reflectivity or
emissivity which vary with viewing angle. As off-nadir remote sensing platforms
become increasingly prevalent, techniques robust to changing viewing geometries
are desired. A technique leveraging polarimetric hyperspectral imaging (P-HSI),
to estimate complex index of refraction, N(nu), an inherent material property, is
presented. The imaginary component of N(nu) is modeled using a small number of
"knot" points and interpolation at in-between frequencies nu. The real component
is derived via the Kramers-Kronig relationship. P-HSI measurements of blackbody
radiation scattered off of a smooth quartz window show that N(nu) can be
retrieved to within 0.08 RMS error between 875 cm-1 <= nu <= 1250
cm-1. P-HSI emission measurements of a heated smooth Pyrex beaker also
enable successful N(nu) estimates, which are also invariant to object
temperature.
PMID- 27505761
TI - Consequences of femtosecond laser filament generation conditions in standoff
laser induced breakdown spectroscopy.
AB - The combination of femtosecond laser filament ablation and emission spectroscopy
is a potential analytical tool for standoff characterization of samples of
interest. We compare the emission features and physical conditions of plasmas
generated from metal targets using either by loosely focused femtosecond
filaments or by lens-free filaments. Our results show that the filament
generation conditions influence the plasma properties appreciably which include
the atomic and molecular emission features, persistence and plasma fundamentals
(temperature and density). The loosely focused fs pulse filaments are found to
generate ablation plumes with higher temperature and density along with increased
persistence compared to plumes generated by lens-free filaments.
PMID- 27505762
TI - Enhanced light extraction efficiency of OLEDs with quasiperiodic diffraction
grating layer.
AB - We presented enhanced light extraction efficiency of organic light emitting
diodes (OLEDs) cells with a nano-sized diffraction grating layer. Various
diffraction gratings of different morphologies including linear, cubic, hexagonal
and quasiperiodic patterns were fabricated by multiplexing light interference
exposure on an azobenzene thin film. The effect of diffraction grating layer on
device performances including luminous properties and quantum efficiency was
investigated. In contrast to periodic grating patterns, the quasiperiodic
structures leading broadband light extraction resulted in improved external
quantum efficiency and power efficiency by 73% and 63%, respectively, compared to
conventional OLED with flat surface of glass substrate.
PMID- 27505763
TI - High-resolution fiber Bragg grating based transverse load sensor using microwave
photonics filtering technique.
AB - In this paper, a new fiber Bragg grating (FBG) sensor exploiting microwave
photonics filter technique for transverse load sensing is firstly proposed and
experimentally demonstrated. A two-tap incoherent notch microwave photonics
filter (MPF) based on a transverse loaded FBG, a polarization beam splitter
(PBS), a tunable delay line (TDL) and a length of dispersion compensating fiber
(DCF) is demonstrated. The frequency response of the filter with respect to the
transverse load is studied. By detecting the resonance frequency shifts of the
notch MPF, the transverse load can be determined. The theoretical and
experimental results show that the proposed FBG sensor has a higher resolution
than traditional methods based on optical spectrum analysis. The sensitivity of
the sensor is measured to be as high as 2.5 MHz/N for a sensing fiber with a
length of 18mm. Moreover, the sensitivity can be easily adjusted.
PMID- 27505764
TI - Banded all-optical OFDM super-channels with low-bandwidth receivers.
AB - We propose a banded all-optical orthogonal frequency division multiplexing (AO
OFDM) transmission system based on synthesising a number of truncated sinc-shaped
subcarriers for each sub-band. This approach enables sub-band by sub-band
reception and therefore each receiver's electrical bandwidth can be significantly
reduced compared with a conventional AO-OFDM system. As a proof-of-concept
experiment, we synthesise 6 * 10-Gbaud subcarriers in both conventional and
banded AO-OFDM systems. With a limited receiver electrical bandwidth, the
experimental banded AO-OFDM system shows 2-dB optical signal to noise ratio
(OSNR) benefit over conventional AO-OFDM at the 7%-overhead forward error
correction (FEC) threshold. After transmission over 800-km of single-mode fiber,
~3-dB improvement in Q-factor can be achieved at the optimal launch power at a
cost of increasing the spectral width by 14%.
PMID- 27505765
TI - Highly sensitive and reconfigurable fiber optic current sensor by optical
recirculating in a fiber loop.
AB - An advanced fiber optic current sensor (FOCS) is proposed based on recirculating
fiber loop architecture for significantly enhancing the current sensitivity. The
recirculating loop is constructed by a 2X2 optical switch and the standard single
mode fiber (SSMF) is used as the sensing head. The proposed FOCS is coupler-free
with low insertion loss which results in a significantly improved current
sensitivity. We experimentally obtained a sensitivity of 11.5 degrees/A for 1-Km
SSMF FOCS and a sensitivity of 21.2 degrees/A for 500-m SSMF FOCS, both of which
have been enhanced by more than ten times. The flexible switch control of
recirculating can support the FOCS to work for different current scenarios with
the same system and thus reconfigurable operation of the FOCS has been achieved.
The significantly enhanced high sensitivity with reconfigurable operation
capability makes the proposed FOCS a promising method for practical applications.
PMID- 27505766
TI - Removing image artefacts in wire array metamaterials.
AB - Hyperlenses and hyperbolic media endoscopes can overcome the diffraction limit by
supporting propagating high spatial frequency extraordinary waves. While
hyperlenses can resolve subwavelength details far below the diffraction limit,
images obtained from them are not perfect: resonant high spatial frequency slab
modes as well as diffracting ordinary waves cause image distortion and artefacts.
In order to use hyperlenses as broad-band subwavelength imaging devices, it is
thus necessary to avoid or correct such unwanted artefacts. Here we introduce
three methods, namely convolution, field averaging, and power averaging, to
remove imaging artefacts over wide frequency bands, and numerically demonstrate
their effectiveness based on simulations of a wire medium endoscope. We also
define a projection in spatial Fourier space to effectively filter out all
ordinary waves, leading to considerable reduction in image distortion. These
methods are outlined and demonstrated for simple and complex apertures.
PMID- 27505767
TI - Broadly tunable mode-locked Ho:YAG ceramic laser around 2.1 um.
AB - A passively mode-locked Ho:YAG ceramic laser around 2.1 um is demonstrated using
GaSb-based near-surface SESAM as saturable absorber. Stable and self-starting
mode-locked operation is realized in the entire tuning range from 2059 to 2121
nm. The oscillator operated at 82 MHz with a maximum output power of 230 mW at
2121 nm. The shortest pulses with duration of 2.1 ps were achieved at 2064 nm. We
also present spectroscopic properties of Ho:YAG ceramics at room temperature.
PMID- 27505768
TI - Remote and in situ sensing products in chemical reaction using a flexible
terahertz pipe waveguide.
AB - The feasibility of remote chemical detection is experimentally demonstrated by
using a Teflon pipe as a scanning arm in a continuous-terahertz wave sensing and
imaging system. Different tablets with distinct mixed ratios of aluminum and
polyethylene powders are well distinguished by measuring the power reflectivities
of 0.4 THz wave associated with their distinct terahertz refractive indices.
Given its refractive index sensitivity and fast response, the reflective
terahertz sensing system can be used to real-time trace and quantitatively
analyze the ammonium-chloride aerosols produced by the chemical reaction between
hydrochloric acid and ammonia vapors. With a tightly focusing terahertz beam
spot, the spatial and concentration distributions of the generated chemical
product are successfully mapped out by the 1D scan of the flexible pipe probe. In
consideration of the responsitivity, power stability, and focused spot size of
the system, its detection limit for the ammonium-chloride aerosol is estimated to
be approximately 165 nmol/mm2. The reliable and compact terahertz pipe
scan system is potentially suitable for practical applications, such as
biomedical or industrial fiber endoscopy.
PMID- 27505769
TI - High efficiency near diffraction-limited mid-infrared flat lenses based on
metasurface reflectarrays.
AB - We report the first demonstration of a mid-IR reflection-based flat lens with
high efficiency and near diffraction-limited focusing. Focusing efficiency as
high as 80%, in good agreement with simulations (83%), has been achieved at 45
degrees incidence angle at lambda = 4.6 MUm. The off-axis geometry considerably
simplifies the optical arrangement compared to the common geometry of normal
incidence in reflection mode which requires beam splitters. Simulations show that
the effects of incidence angle are small compared to parabolic mirrors with the
same NA. The use of single-step photolithography allows large scale fabrication.
Such a device is important in the development of compact telescopes, microscopes,
and spectroscopic designs.
PMID- 27505770
TI - Multiocular image sensor with on-chip beam-splitter and inner meta-micro-lens for
single-main-lens stereo camera.
AB - We developed multiocular 1/3-inch 2.75-MUm-pixel-size 2.1M- pixel image sensors
by co-design of both on-chip beam-splitter and 100-nm-width 800-nm-depth
patterned inner meta-micro-lens for single-main-lens stereo camera systems. A
camera with the multiocular image sensor can capture horizontally one-dimensional
light filed by both the on-chip beam-splitter horizontally dividing ray according
to incident angle, and the inner meta-micro-lens collecting the divided ray into
pixel with small optical loss. Cross-talks between adjacent light field images of
a fabricated binocular image sensor and of a quad-ocular image sensor are as low
as 6% and 7% respectively. With the selection of two images from one-dimensional
light filed images, a selective baseline for stereo vision is realized to view
close objects with single-main-lens. In addition, by adding multiple light field
images with different ratios, baseline distance can be tuned within an aperture
of a main lens. We suggest the electrically selective or tunable baseline stereo
vision to reduce 3D fatigue of viewers.
PMID- 27505771
TI - Achromatic and athermal lens design by redistributing the element powers on an
athermal glass map.
AB - We propose a new graphical method for selecting a pair of optical and housing
materials to simultaneously achromatize and athermalize a multilens system. To
obtain the material combination using an athermal glass map, the material
suitable for housing is graphically selected, and then the powers of elements
constituting an equivalent single lens are redistributed. Although a material
combination does not exist, we can continuously change the power of each element.
Thus, we can reasonably identify a pair of optical and housing materials that
simultaneously satisfies achromatic and athermal conditions. By applying this
method to design a Tessar lens, the chromatic and thermal defocuses are reduced
to less than the depth of focus, over the specified waveband and temperature
ranges.
PMID- 27505772
TI - Accidental degeneracy in photonic bands and topological phase transitions in two
dimensional core-shell dielectric photonic crystals.
AB - A simple core-shell two-dimensional photonic crystal is studied where the
triangular lattice symmetry and the C6 point group symmetry give rich
physics in accidental touching points of photonic bands. We systematically
evaluate different types of accidental nodal points at the Brillouin zone center
for transverse-magnetic harmonic modes when the geometry and permittivity of the
core-shell material are continuously tuned. The accidental nodal points can have
different dispersions and topological properties (i.e., Berry phases). These
accidental nodal points can be the critical states lying between a topological
phase and a normal phase of the photonic crystal. They are thus very important
for the study of topological photonic states. We show that, without breaking time
reversal symmetry, by tuning the geometry of the core-shell material, a phase
transition into the photonic quantum spin Hall insulator can be achieved. Here
the "spin" is defined as the orbital angular momentum of a photon. We study the
topological phase transition as well as the properties of the edge and bulk
states and their application potentials in optics.
PMID- 27505773
TI - Trapping two types of particles by modified circular Airy beams.
AB - The radiation force of modified circular Airy beams (MCAB) exerted on both a high
refractive-index particle and a low-refractive-index particle are analyzed in
this paper. Our results show that the two kinds of particles can be
simultaneously stably trapped by MCAB at different positions. Compared with the
common circular Airy beams (CAB) with the same parameters, trapping forces on the
two kinds of particles are greatly increased because of the enhanced abruptly
autofocusing property and the appearance of hollow region in MCAB. The trapping
forces can be modulated by varying parameters of MCAB, and it is important to
choose appropriate parameters to trap particles in practice.
PMID- 27505774
TI - Propagation of the power-exponent-phase vortex beam in paraxial ABCD system.
AB - The general analytical formula for the propagation of the power-exponent-phase
vortex (PEPV) beam through a paraxial ABCD optical system is derived. On that
basis the evolution of the intensity distribution of such a beam in free space
and the focusing system is investigated. In addition, some experiments are
carried out, which verify the theoretical predictions. Both of the theoretical
and experimental results show that the beam's profile can be modulated by the
topological charge and the power order of the PEPV beam.
PMID- 27505775
TI - Capacity achieving nonbinary LDPC coded non-uniform shaping modulation for
adaptive optical communications.
AB - A mutual information inspired nonbinary coded modulation design with non-uniform
shaping is proposed. Instead of traditional power of two signal constellation
sizes, we design 5-QAM, 7-QAM and 9-QAM constellations, which can be used in
adaptive optical networks. The non-uniform shaping and LDPC code rate are jointly
considered in the design, which results in a better performance scheme for the
same SNR values. The matched nonbinary (NB) LDPC code is used for this scheme,
which further improves the coding gain and the overall performance. We analyze
both coding performance and system SNR performance. We show that the proposed NB
LDPC-coded 9-QAM has more than 2dB gain in symbol SNR compared to traditional
LDPC-coded star-8-QAM. On the other hand, the proposed NB LDPC-coded 5-QAM and 7
QAM have even better performance than LDPC-coded QPSK.
PMID- 27505776
TI - On the resilience of scalar and vector vortex modes in turbulence.
AB - Free-space optical communication with spatial modes of light has become topical
due to the possibility of dramatically increasing communication bandwidth via
Mode Division Multiplexing (MDM). While both scalar and vector vortex modes have
been used as transmission bases, it has been suggested that the latter is more
robust in turbulence. Using orbital angular momentum as an example, we
demonstrate theoretically and experimentally that the crosstalk due to turbulence
is the same in the scalar and vector basis sets of such modes. This work brings
new insights about the behaviour of vector and scalar modes in turbulence, but
more importantly it demonstrates that when considering optimal modes for MDM, the
choice should not necessarily be based on their vectorial nature.
PMID- 27505777
TI - Improved halftoning method for autostereoscopic display based on float grid
division multiplexing.
AB - Autostereoscopic printing is one of the most common ways for three-dimensional
display, because it can present finer results by printing higher dots per inches
(DPI). However, there are some problems for current methods. First, errors caused
by dislocation between integer grids and non-customized lenticular lens result in
severe vision quality. Second, the view-number and gray-level cannot be set
arbitrarily. In this paper, an improved halftoning method for autostereoscopic
printing based on float grid-division multiplexing (fGDM) is proposed. FGDM
effectively addresses above two problems. GPU based program of fGDM is enabled to
achieve the result very fast. Films with lenticular lens array are implemented in
experiments to verify the effectiveness of proposed method which provides an
improved three-dimensional performance, compared with the AM screening and random
screening.
PMID- 27505778
TI - Rapid and economical data acquisition in ultrafast frequency-resolved
spectroscopy using choppers and a microcontroller.
AB - Spectrometers and cameras are used in ultrafast spectroscopy to achieve high
resolution in both time and frequency domains. Frequency-resolved signals from
the camera pixels cannot be processed by common lock-in amplifiers, which have
only a limited number of input channels. Here we demonstrate a rapid and
economical method that achieves the function of a lock-in amplifier using
mechanical choppers and a programmable microcontroller. We demonstrate the
method's effectiveness by performing a frequency-resolved pump-probe measurement
on the dye Nile Blue in solution.
PMID- 27505779
TI - High-repetition-rate and high-photon-flux 70 eV high-harmonic source for
coincidence ion imaging of gas-phase molecules.
AB - Unraveling and controlling chemical dynamics requires techniques to image
structural changes of molecules with femtosecond temporal and picometer spatial
resolution. Ultrashort-pulse x-ray free-electron lasers have significantly
advanced the field by enabling advanced pump-probe schemes. There is an
increasing interest in using table-top photon sources enabled by high-harmonic
generation of ultrashort-pulse lasers for such studies. We present a novel high
harmonic source driven by a 100 kHz fiber laser system, which delivers
1011 photons/s in a single 1.3 eV bandwidth harmonic at 68.6 eV. The
combination of record-high photon flux and high repetition rate paves the way for
time-resolved studies of the dissociation dynamics of inner-shell ionized
molecules in a coincidence detection scheme. First coincidence measurements on
CH3I are shown and it is outlined how the anticipated advancement of
fiber laser technology and improved sample delivery will, in the next step, allow
pump-probe studies of ultrafast molecular dynamics with table-top XUV-photon
sources. These table-top sources can provide significantly higher repetition
rates than the currently operating free-electron lasers and they offer very high
temporal resolution due to the intrinsically small timing jitter between pump and
probe pulses.
PMID- 27505780
TI - Interaction potential between discrete solitons in waveguide arrays.
AB - Using a variational approach, we obtained the interaction potential between two
discrete solitons in optical waveguide arrays. The resulting potential bears the
two features of soliton-soliton and soliton-waveguide interaction potentials
where the former is similar to that of the continuum case and the latter is
similar to the effective Pierls-Nabarro potential. The interplay between the two
interaction potentials is investigated by studying its effect on the soliton
molecule formation. It is found that the two solitons bind if their initial
separation equals an odd number of waveguides, while they do not bind if their
separation is an even number, which is a consequence of the two solitons being
both either at the intersites (unstable) or being onsite (stable). We derived the
equations of motion for the solitons' centre of mass and relative separation and
provided analytic solutions for some specific cases. Favourable agreement between
the analytical and numerical interaction potentials is obtained. Possible
applications of our results to all-optical logic gates are pointed out.
PMID- 27505781
TI - Micromanipulation of InP lasers with optoelectronic tweezers for integration on a
photonic platform.
AB - The integration of light sources on a photonic platform is a key aspect of the
fabrication of self-contained photonic circuits with a small footprint that does
not have a definitive solution yet. Several approaches are being actively
researched for this purpose. In this work we propose optoelectronic tweezers for
the manipulation and integration of light sources on a photonic platform and
report the positional and angular accuracy of the micromanipulation of standard
Fabry-Perot InP semiconductor laser die. These lasers are over three orders of
magnitude bigger in volume than any previously assembled with optofluidic
techniques and the fact that they are industry standard lasers makes them
significantly more useful than previously assembled microdisk lasers. We measure
the accuracy to be 2.5 +/- 1.4 um and 1.4 +/- 0.4 degrees and conclude that
optoelectronic tweezers are a promising technique for the micromanipulation and
integration of optoelectronic components in general and semiconductor lasers in
particular.
PMID- 27505782
TI - Enhancement of optical polarization degree of AlGaN quantum wells by using
staggered structure.
AB - Staggered AlGaN quantum wells (QWs) are designed to enhance the transverse
electric (TE) polarized optical emission in deep ultraviolet (DUV) light-
emitting diodes (LED). The optical polarization properties of the conventional
and staggered AlGaN QWs are investigated by a theoretical model based on the k.p
method as well as polarized photoluminescence (PL) measurements. Based on an
analysis of the valence subbands and momentum matrix elements, it is found that
AlGaN QWs with step-function-like Al content in QWs offers much stronger TE
polarized emission in comparison to that from conventional AlGaN QWs.
Experimental results show that the degree of the PL polarization at room
temperature can be enhanced from 20.8% of conventional AlGaN QWs to 40.2% of
staggered AlGaN QWs grown by MOCVD, which is in good agreement with the
theoretical simulation. It suggests that polarization band engineering via
staggered AlGaN QWs can be well applied in high efficiency AlGaN-based DUV LEDs.
PMID- 27505783
TI - Optimization of multilayered nanotubes for maximal scattering cancellation.
AB - An optimization for multilayered nanotubes that minimizes the scattering
efficiency for a given polarization is derived. The cylindrical nanocavities have
a radially periodic distribution, and the marginal layers that play a crucial
role particularly in the presence of nonlocalities are disposed to reduce the
scattering efficiency up to two orders of magnitude in comparison with previous
proposals. The predominant causes leading to such invisibility effect are
critically discussed.
PMID- 27505784
TI - Performance and noise analysis of optical microresonator-based biochemical
sensors using intensity detection.
AB - Optical microcavity sensors using intensity detection open up the possibility to
realize fully integrated high-performance sensing devices, which are significant
for both fundamental study of molecular interaction and rapid disease diagnosis.
Although the performance of microresonator-based sensors has been studied
focusing on the resonance-tracking method, the situation can be much different
for intensity-detection sensors. Here we conducted a systematically investigation
on the noises sources in intensity detection scheme and their influences on key
performance parameters, e.g., signal-to-noise ratio (SNR), limit-of-detection
(LOD), and detection range, for various sensors configurations. Especially, the
trade-off between SNR and LOD is identified and theoretically analyzed. With
experiment noises taken into consideration, our work aims to provide design
guidelines for integrated microresonator sensors with optimized performance.
PMID- 27505785
TI - VUV and XUV reflectance of optically coated mirrors for selection of high
harmonics.
AB - We report the reflectance, ~1 degrees from normal incidence, of six different
mirrors as a function of photon energy, using monochromatic vacuum ultraviolet
(VUV) and extreme ultraviolet (XUV) radiation with energies between 7.5 eV and
24.5 eV. The mirrors examined included both single and multilayer optical
coatings, as well as an uncoated substrate. We discuss the performance of each
mirror, paying particular attention to the potential application of suppression
and selection of high-order harmonics of a Ti:sapphire laser.
PMID- 27505786
TI - Integrated nonlinear interferometer with wavelength multicasting functionality.
AB - Nonlinear interference based on four wave mixing (FWM) is extremely attractive
due to its phase sensitivity. On the other hand, wavelength multicasting, which
supports data point-to-multipoint connections, is a key functionality to increase
the network efficiency and simplify the transmitter and receiver in the
wavelength-division multiplexing systems. We propose and experimentally
demonstrate a nonlinear interferometer with wavelength multicasting functionality
based on single-stage FWM in an integrated silicon waveguide. With a three-pump
and dual-signal input, four phase sensitive idlers are obtained at the
interferometer output. For a proof-of-concept application, we further
theoretically demonstrate the multicasting logic exclusive-OR (XOR) gate for both
intensity and phase modulated signals. The proposed scheme would be potentially
applied in various on-chip applications for future optical communication system.
PMID- 27505787
TI - Design of plasmonic photodetector with high absorptance and nano-scale active
regions.
AB - We propose a novel plasmonic photodetector with high responsivity, utilizing nano
scale active regions. This design can be applied to diverse materials (group III
V or IV materials) and different operation wavelengths covering the O-U bands.
The periodic structure utilizing Surface Plasmon Polariton Bloch Waves (SPP-BWs)
has low optical power loss. FDTD simulation shows an absorptance of 74.4% which
means a responsivity of about 0.74 A/W at 1550 nm. The low capacitance brings low
noise, reduced power consumption, and a high electrical bandwidth which is
estimated to be 140 GHz. Among the plasmonic PDs with inherent high speeds but
low responsivities, our design makes the obvious progress on improving the
absorptance.
PMID- 27505788
TI - Reconfigurable hybrid metamaterial waveguide system at terahertz regime.
AB - We propose an optically controlled reconfigurable hybrid metamaterial waveguide
system at terahertz frequencies, which consists of a two dimensional gold cut
wire array deposited on top of a dielectric slab waveguide. Numerical findings
reveal that this device is able to realize dynamic transformation from double
electromagnetically induced transparency like material to ultra-narrow band
guided mode resonance (GMR) filter by controlling the optically excited free
carriers in gallium arsenide pads inserted between the gold cut wires. During
this reconfiguration process of resonance modes, high quality factors up to ~104
and ~118 for the two EIT-like peaks and up to ~578 for the GMR filter are
obtained.
PMID- 27505789
TI - High-purity 60GHz band millimeter-wave generation based on optically injected
semiconductor laser under subharmonic microwave modulation.
AB - Based on an optically injected semiconductor laser (OISL) operating at period-one
(P1) nonlinear dynamical state, high-purity millimeter-wave generation at 60 GHz
band is experimentally demonstrated via 1/4 and 1/9 subharmonic microwave
modulation (the order of subharmonic is with respect to the frequency fc of the
acquired 60 GHz band millimeter-wave but not the fundamental frequency f0 of P1
oscillation). Optical injection is firstly used to drive a semiconductor laser
into P1 state. For the OISL operates at P1 state with a fundamental frequency f0
= 49.43 GHz, by introducing 1/4 subharmonic modulation with a modulation
frequency of fm = 15.32 GHz, a 60 GHz band millimeter-wave with central frequency
fc = 61.28 GHz ( = 4fm) is experimentally generated, whose linewidth is below 1.6
kHz and SSB phase noise at offset frequency 10 kHz is about -96 dBc/Hz. For fm is
varied between 13.58 GHz and 16.49 GHz, fc can be tuned from 54.32 GHz to 65.96
GHz under matched modulation power Pm. Moreover, for the OISL operates at P1
state with f0 = 45.02 GHz, a higher order subharmonic modulation (1/9) is
introduced into the OISL for obtaining high-purity 60 GHz band microwave signal.
With (fm, Pm) = (7.23 GHz, 13.00 dBm), a microwave signal at 65.07 GHz ( = 9fm)
with a linewidth below 1.6 kHz and a SSB phase noise less than -98 dBc/Hz is
experimentally generated. Also, the central frequency fc can be tuned in a
certain range through adjusting fm and selecting matched Pm.
PMID- 27505790
TI - Manipulation of wavefront using helical metamaterials.
AB - Helical metamaterials, a kind of 3-dimensional structure, has relatively strong
coupling effect among the helical nano-wires. Therefore, it is expected to be a
good candidate for generating phase shift and controlling wavefront with high
efficiency. In this paper, using the finite-difference time-domain (FDTD) method,
we studied the phase shift properties in the helical metamaterials. It is found
that the phase shift occurs for both transmitted and reflected light waves. And
the maximum of reflection coefficients can reach over 60%. In addition, the phase
shift (phi) is dispersionless in the range of 600 nm to 860 nm, that is, it is
only dominated by the initial angle (theta) of the helix. The relationship
between them is phi = +/- 2theta. Using Jones calculus we give a further
explanation for these properties. Finally, by arranging the helixes in an array
with a constant phase gradient, the phenomenon of anomalous refraction was also
observed in a broad wavelength range.
PMID- 27505791
TI - Snapshot fan beam coded aperture coherent scatter tomography.
AB - We use coherently scattered X-rays to measure the molecular composition of an
object throughout its volume. We image a planar slice of the object in a single
snapshot by illuminating it with a fan beam and placing a coded aperture between
the object and the detectors. We characterize the system and demonstrate a
resolution of 13 mm in range and 2 mm in cross-range and a fractional momentum
transfer resolution of 15%. In addition, we show that this technique allows a
100x speedup compared to previously-studied pencil beam systems using the same
components. Finally, by scanning an object through the beam, we image the full 4
dimensional data cube (3 spatial and 1 material dimension) for complete
volumetric molecular imaging.
PMID- 27505792
TI - Ghost imaging with different frequencies through non-degenerated four-wave
mixing.
AB - As a novel imaging method, ghost imaging has been widely explored in various
fields of research, such as lensless ghost imaging, computational ghost imaging,
turbulence-free ghost imaging. Recently, ghost imaging in non-degenerated system
with pseudo-thermal light has been discussed theoretically, however, to our best
knowledge, no experimental evidence has been proven yet. In this paper, we
propose a new approach to realize ghost imaging with different frequencies, which
are generated through a non-degenerated four-wave mixing(FWM) process in Rb
vapor. In our experiment, by employing pseudo-thermal light as the probe beam, we
found that the generated FWM signal has a strong second-order correlation with
the original thermal light. On basis of that, we successfully implement non
degenerate ghost imaging, and reconstruct highly similar images of objects.
PMID- 27505793
TI - Digital polarization holography advancing geometrical phase optics.
AB - Geometrical phase or the fourth generation (4G) optics enables realization of
optical components (lenses, prisms, gratings, spiral phase plates, etc.) by
patterning the optical axis orientation in the plane of thin anisotropic films.
Such components exhibit near 100% diffraction efficiency over a broadband of
wavelengths. The films are obtained by coating liquid crystalline (LC) materials
over substrates with patterned alignment conditions. Photo-anisotropic materials
are used for producing desired alignment conditions at the substrate surface. We
present and discuss here an opportunity of producing the widest variety of "free
form" 4G optical components with arbitrary spatial patterns of the optical
anisotropy axis orientation with the aid of a digital spatial light polarization
converter (DSLPC). The DSLPC is based on a reflective, high resolution spatial
light modulator (SLM) combined with an "ad hoc" optical setup. The most
attractive feature of the use of a DSLPC for photoalignment of nanometer thin
photo-anisotropic coatings is that the orientation of the alignment layer, and
therefore of the fabricated LC or LC polymer (LCP) components can be specified on
a pixel-by-pixel basis with high spatial resolution. By varying the optical
magnification or de-magnification the spatial resolution of the photoaligned
layer can be adjusted to an optimum for each application. With a simple "click"
it is possible to record different optical components as well as arbitrary
patterns ranging from lenses to invisible labels and other transparent labels
that reveal different images depending on the side from which they are viewed.
PMID- 27505794
TI - Experimental demonstration of an adaptive architecture for direct spectral
imaging classification.
AB - Spectral imaging is a powerful tool for providing in situ material classification
across a spatial scene. Typically, spectral imaging analyses are interested in
classification, though often the classification is performed only after
reconstruction of the spectral datacube. We present a computational spectral
imaging system, the Adaptive Feature-Specific Spectral Imaging Classifier (AFSSI
C), which yields direct classification across the spatial scene without
reconstruction of the source datacube. With a dual disperser architecture and a
programmable spatial light modulator, the AFSSI-C measures specific projections
of the spectral datacube which are generated by an adaptive Bayesian
classification and feature design framework. We experimentally demonstrate
multiple order-of-magnitude improvement of classification accuracy in low signal
to-noise (SNR) environments when compared to legacy spectral imaging systems.
PMID- 27505795
TI - Analysis of optical directional couplers using shortcuts to adiabaticity.
AB - In this paper, we propose the use of the invariant based shortcuts to
adiabaticity for the analysis of directional couplers. By describing the
dynamical evolution of the system using the eigenstates of the invariant through
new parameterizations, the system stability against errors in coupling
coefficient and propagation constants mismatch is connected with the new
parameters, which can be linked back to system parameters through inverse
engineering. The merits and limitations of the conventional tapered directional
coupler designs with various window functions are obtained through the analysis.
We then propose an optimal design of compact directional couplers that is stable
against errors in input wavelength and coupling coefficient simultaneously. The
designed directional coupler has better tolerance, as compared to the
conventional resonant couplers with smooth shape functions of Hamming and
Blackman. These results are verified by beam propagation simulations.
PMID- 27505796
TI - Optical Bloch oscillations and Zener tunneling of Airy beams in ionic-type
photonic lattices.
AB - We report on the existence of optical Bloch oscillations (OBOs) and Zener
tunneling (ZT) of Airy beams in ionic-type photonic lattices with a refractive
index ramp. Different from their counterparts in uniform lattices, Airy beams
undergoing OBOs show an alternatively switched concave and convex trajectory as
well as a periodical revival of input beam profiles. Moreover, the ionic-type
photonic lattice established in photorefractive crystal exhibits a reconfigurable
lattice structure, which provides a flexible way to tune the amplitude and period
of the OBOs. Remarkably, it is demonstrated that the band gap of the lattice can
be readily controlled by rotating the lattice inducing beam, which forces the ZT
rate to follow two significant different decay curves amidst decreasing index
gradient. Our results open up new possibilities for all-optical switching,
routing and manipulation of Airy beams.
PMID- 27505797
TI - Bulk magnetic terahertz metamaterials based on dielectric microspheres.
AB - Rigid metamaterials were prepared by embedding TiO2 microspheres into
polyethylene. These structures exhibit a series of Mie resonances where the
lowest-frequency one is associated with a strong dispersion in the effective
magnetic permeability. Using time-domain terahertz spectroscopy, we
experimentally demonstrated the magnetic nature of the observed resonance. The
presented approach shows a way for low-cost massive fabrication of mechanically
stable terahertz metamaterials based on dielectric microresonators.
PMID- 27505798
TI - Membrane distributed-reflector laser integrated with SiOx-based spot-size
converter on Si substrate.
AB - We demonstrate monolithic integration of a 50-MUm-long-cavity membrane
distributed-reflector laser with a spot-size converter, consisting of a tapered
InP wire waveguide and an SiOx waveguide, on SiO2/Si substrate. The
device exhibits 9.4-GHz/mA0.5 modulation efficiency with a 2.2-dB
fiber coupling loss. We demonstrate 25.8-Gbit/s direct modulation with a bias
current of 2.5 mA, resulting in a low energy cost of 132 fJ/bit.
PMID- 27505799
TI - Periodic nonlinear Fourier transform for fiber-optic communications, Part I:
theory and numerical methods.
AB - In this work, we introduce the periodic nonlinear Fourier transform (PNFT) method
as an alternative and efficacious tool for compensation of the nonlinear
transmission effects in optical fiber links. In the Part I, we introduce the
algorithmic platform of the technique, describing in details the direct and
inverse PNFT operations, also known as the inverse scattering transform for
periodic (in time variable) nonlinear Schrodinger equation (NLSE). We pay a
special attention to explaining the potential advantages of the PNFT-based
processing over the previously studied nonlinear Fourier transform (NFT) based
methods. Further, we elucidate the issue of the numerical PNFT computation: we
compare the performance of four known numerical methods applicable for the
calculation of nonlinear spectral data (the direct PNFT), in particular, taking
the main spectrum (utilized further in Part II for the modulation and
transmission) associated with some simple example waveforms as the quality
indicator for each method. We show that the Ablowitz-Ladik discretization
approach for the direct PNFT provides the best performance in terms of the
accuracy and computational time consumption.
PMID- 27505800
TI - Periodic nonlinear Fourier transform for fiber-optic communications, Part II:
eigenvalue communication.
AB - In this paper we propose the design of communication systems based on using
periodic nonlinear Fourier transform (PNFT), following the introduction of the
method in the Part I. We show that the famous "eigenvalue communication" idea [A.
Hasegawa and T. Nyu, J. Lightwave Technol. 11, 395 (1993)] can also be
generalized for the PNFT application: In this case, the main spectrum attributed
to the PNFT signal decomposition remains constant with the propagation down the
optical fiber link. Therefore, the main PNFT spectrum can be encoded with data in
the same way as soliton eigenvalues in the original proposal. The results are
presented in terms of the bit-error rate (BER) values for different modulation
techniques and different constellation sizes vs. the propagation distance,
showing a good potential of the technique.
PMID- 27505801
TI - Lambertian thermal emitter based on plasmonic enhanced absorption.
AB - In this paper, a narrow band thermal emission at 10 MUm is demonstrated using a
one dimensional metasurface. The proposed metasurface structure provides magnetic
resonance mode that enhances the phonon absorption of SiO2. The
proposed metasurface thermal emitter shows a Lambertian distribution.
Additionally, 5.8-folds enhancement of emissivity is achieved by optimizing the
cavity thickness of the metasurfaces. This type of thermal emitter will be useful
for IR sensing applications.
PMID- 27505802
TI - Complete hyperentangled Bell state analysis for polarization and time-bin
hyperentanglement.
AB - We present a complete hyperentangled Bell state analysis protocol for two-photon
four-qubit states that are simultaneously entangled in the polarization and time
bin degrees of freedom. The 16 hyperentangled states can be unambiguously
distinguished via two steps. In the first step, the polarization entangled state
is distinguished deterministically and nondestructively with the help of the
cross-Kerr nonlinearity. Then, in the second step, the time-bin state is analyzed
with the aid of the polarization entanglement. We also discuss the applications
of our protocol for quantum information processing. Compared with
hyperentanglement in polarization and spatial-mode degrees of freedom, the
polarization and time-bin hyperentangled states provide savings in quantum
resources since there is no requirement for two spatial modes for each photon.
This is the first complete hyperentangled Bell state analysis scheme for
polarization and time-bin hyperentangled states, and it can provide new avenues
for high-capacity, long-distance quantum communication.
PMID- 27505803
TI - High-quality-factor planar optical cavities with laterally stopped, slowed, or
reversed light.
AB - In a planar optical cavity, the resonance frequencies increase as a function of
in-plane wavevector according to a standard textbook formula. This has well-known
consequences in many different areas of optics, from the shifts of etalon peaks
at non-normal angles, to the properties of transverse modes in laser diodes, to
the effective mass of microcavity photons, and so on. However, this standard
formula is valid only when the reflection phase of each cavity mirror is
approximately independent of angle. There is a certain type of mirror-a
subwavelength dielectric grating near a guided mode resonance-with not only a
strongly angle-dependent reflection phase, but also very high reflectance and low
losses. Simulations show that by using such mirrors, high-quality-factor planar
cavities can be designed that break all these textbook rules, leading to resonant
modes that are slow, stopped or even backward-propagating in the in-plane
direction. In particular, we demonstrate experimentally high-Q planar cavities
whose resonance frequency is independent of in-plane wavevector-i.e., the
resonant modes have zero in-plane group velocity, for one polarization but both
in-plane directions. We discuss potential applications in various fields
including lasers, quantum optics, and exciton-polariton condensation.
PMID- 27505804
TI - Dual-wavelength digital holography with a single low-coherence light source.
AB - We propose a measurement system using dual-wavelength digital holography and low
coherence interferometry to measure micro- and nanostructure surface heights. To
achieve an extended axial step-measurement range and better image quality, a
single light-emitting diode generates two distinct light sources by filtering
different center wavelengths and narrower bandwidths. The system can measure
surface profile with higher step heights and lower speckle noise in a large field
of-view. Using single-source lighting and a simple configuration, the method
supports compactly configured and lower-cost surface-topography measurement
systems applicable in various fields. Experimental results for a standard step
sample verify the system's performance.
PMID- 27505805
TI - Light coupling between vertical III-As nanowires and planar Si photonic
waveguides for the monolithic integration of active optoelectronic devices on a
Si platform.
AB - We present a new concept for the optical interfacing between vertical III-As
nanowires and planar Si waveguides. The nanowires are arranged in a two
dimensional array which forms a grating structure on top of the waveguide. This
grating enables light coupling in both directions between the components made
from the two different material classes. Numerical simulations show that this
concept permits a light extraction efficiency from the waveguide larger than 45%
and a light insertion efficiency larger than 35%. This new approach would allow
the monolithic integration of nanowire-based active optoelectronics devices, like
photodetectors and light sources, on the Si photonics platform.
PMID- 27505806
TI - Direct modulation of 1.3 MUm quantum dot lasers on silicon at 60 degrees C.
AB - We demonstrate direct modulation of an InAs/GaAs quantum dot (QD) laser on Si. A
Fabry-Perot QD laser was integrated on Si by an ultraviolet-activated direct
bonding method, and a cavity was formed using cleaved facets without HR/AR
coatings. The bonded laser was operated under continuous-wave pumping at room
temperature with a threshold current of 41 mA and a maximum output power of 30 mW
(single facet). Even with such a simple device structure and fabrication process,
our bonded laser is directly modulated using a 10 Gbps non-return-to-zero signal
with an extinction ratio of 1.9 dB at room temperature. Furthermore, 6 Gbps
modulation with an extinction ratio of 4.5 dB is achieved at temperatures up to
60 degrees C without any current or voltage adjustment. These results of device
performances indicate an encouraging demonstration on III-V QD lasers on Si for
the applications of the photonic integrated circuits.
PMID- 27505807
TI - Optical pulling using evanescent mode in sub-wavelength channels.
AB - Optical evanescent wave in total internal reflection has been widely used in
efficient optical manipulation, where the object is trapped by the intrinsic
intensity gradient of the evanescent wave while transported by the scattering
force along the orthogonal direction. Here, we propose a distinct optical
manipulation scheme using the attenuated modes in subwavelength optical channels,
where both the trapping and transportation forces are along the channel
direction. We create such a mode in a sub-wavelength photonic crystal waveguide
and quantitatively obtain the net pushing and pulling forces, which can overcome
the Brownian motion within a critical length. Due to the presence of the physical
channel, subwavelength trapping on the transverse direction is natural, and
manipulation along bend trajectories is also possible without the assistance of
the self-acceleration beams provided a channel is adopted. This optical
manipulation method can be extended to any other channels that support
attenuation mode, and may provide an alternate way for flexible optical
manipulation.
PMID- 27505808
TI - Pixel-wise absolute phase unwrapping using geometric constraints of structured
light system.
AB - This paper presents a method to unwrap phase pixel by pixel by solely using
geometric constraints of the structured light system without requiring additional
image acquisition or another camera. Specifically, an artificial absolute phase
map, Phimin, at a given virtual depth plane z = zmin, is created from geometric
constraints of the calibrated structured light system; the wrapped phase is pixel
by-pixel unwrapped by referring to Phimin. Since Phimin is defined in the
projector space, the unwrapped phase obtained from this method is absolute for
each pixel. Experimental results demonstrate the success of this proposed novel
absolute phase unwrapping method.
PMID- 27505809
TI - Linearly chirped microwave waveform generation with large time-bandwidth product
by optically injected semiconductor laser.
AB - A scheme for photonic generation of linearly chirped microwave waveforms (LCMWs)
with a large time-bandwidth product (TBWP) is proposed and demonstrated based on
an optically injected semiconductor laser. In the proposed system, the optically
injected semiconductor laser is operated in period-one (P1) oscillation state.
After optical-to-electrical conversion, a microwave signal can be generated with
its frequency determined by the injection strength. By properly controlling the
injection strength, an LCMW with a large TBWP can be generated. The proposed
system has a simple and compact structure. Besides, the center frequency,
bandwidth, as well as the temporal duration of the generated LCMWs can be easily
adjusted. An experiment is carried out. LCMWs with TBWPs as large as
1.2x105 (bandwidth 12 GHz; temporal duration 10 MUs) are successfully
generated. The flexibility for tuning the center frequency, bandwidth and
temporal duration is also demonstrated.
PMID- 27505810
TI - High efficiency double-wavelength dielectric metasurface lenses with dichroic
birefringent meta-atoms.
AB - Metasurfaces are ultrathin optical structures that manipulate optical wavefronts.
Most metasurface devices which deflect light are designed for operation at a
single wavelength, and their function changes as the wavelength is varied. Here
we propose and demonstrate a double-wavelength metasurface based on polarization
dependent dielectric meta-atoms that control the phases of two orthogonal
polarizations independently. Using this platform, we design lenses that focus
light at 915 and 780 nm with perpendicular linear polarizations to the same focal
distance. Lenses with numerical apertures up to 0.7 and efficiencies from 65% to
above 90% are demonstrated. In addition to the high efficiency and numerical
aperture, an important feature of this technique is that the two operation
wavelengths can be chosen to be arbitrarily close. These characteristics make
these lenses especially attractive for fluorescence microscopy applications.
PMID- 27505811
TI - Super-resolving angular rotation measurement using binary-outcome homodyne
detection.
AB - There has been much recent interest in high precision angular rotation
measurement using photon orbital angular momentum to realize super-resolving
angular rotation measurement. It is well known that quantum detection strategies
can obtain a quantum-enhanced performance. Here, we prove that binary-outcome
homodyne detection method can obtain a narrower signal peak, showing better
resolution compared with the existing data processing method. Since the photon
loss is unavoidable in the actual non-ideal optical system, this paper further
discusses the impact of photon loss on the resolution and sensitivity of angular
rotation measurement with binary-outcome homodyne detection method.
PMID- 27505812
TI - Rectilinear lattices of polarization vortices with various spatial polarization
distributions.
AB - In this paper, we propose a type of rectilinear lattices of polarization
vortices, each spot in which has mutually independent, and controllable spatial
polarization distributions. The lattices are generated by two holograms under
special design. In the experiment, the holograms are encoded on two spatial light
modulators, and the results fit very well with theory. Our scheme makes it
possible to generate multiple polarization vortices with various polarization
distributions simultaneously, for instance, radially and azimuthally polarized
beams, and can be used in the domains as polarization-based data transmission
system, optical manufacture, polarization detection and so on.
PMID- 27505813
TI - Design of universal fiber with demonstration of full system reaches over 100G
SR4, 40G sWDM, and 100G CWDM4 transceivers.
AB - Universal fiber has an LP01 mode field diameter approximately matched
to that of standard single mode fiber, while being a multimode fiber. We analyzed
the dependence of the mode field diameter on the core diameter for different core
delta values. Guided by the analysis, a universal fiber having a delta of 1.2%
was fabricated, showing significantly reduced coupling loss of ~2.3 dB with
conventional multimode fiber. We demonstrated that the fiber can transmit with
full system reach in both single mode and VCSEL-based multimode transmissions,
including 100G SR4, 40G sWDM, and 100G CWDM4 for the first time.
PMID- 27505814
TI - Aberrations of the point spread function of a multimode fiber due to partial mode
excitation.
AB - We investigate the point spread function of a multimode fiber. The distortion of
the focal spot created on the fiber output facet is studied for a variety of the
parameters. We develop a theoretical model of wavefront shaping through a
multimode fiber and use it to confirm our experimental results and analyze the
nature of the focal distortions. We show that aberration-free imaging with a
large field of view can be achieved by using an appropriate number of segments on
the spatial light modulator during the wavefront-shaping procedure. The results
describe aberration limits for imaging with multimode fibers as in, e.g.,
microendoscopy.
PMID- 27505815
TI - Massively parallel femtosecond laser processing.
AB - Massively parallel femtosecond laser processing with more than 1000 beams was
demonstrated. Parallel beams were generated by a computer-generated hologram
(CGH) displayed on a spatial light modulator (SLM). The key to this technique is
to optimize the CGH in the laser processing system using a scheme called in
system optimization. It was analytically demonstrated that the number of beams is
determined by the horizontal number of pixels in the SLM NSLM that is
imaged at the pupil plane of an objective lens and a distance parameter
pd obtained by dividing the distance between adjacent beams by the
diffraction-limited beam diameter. A performance limitation of parallel laser
processing in our system was estimated at NSLM of 250 and
pd of 7.0. Based on these parameters, the maximum number of beams in a
hexagonal close-packed structure was calculated to be 1189 by using an analytical
equation.
PMID- 27505816
TI - Mapping the energy density of shaped waves in scattering media onto a complete
set of diffusion modes.
AB - We study the energy density of shaped waves inside a quasi-1D disordered
waveguide. We find that the spatial energy density of optimally shaped waves,
when expanded in the complete set of eigenfunctions of the diffusion equation, is
well described by considering only a few of the lowest eigenfunctions. Taking
into account only the fundamental eigenfunction, the total internal energy inside
the sample is underestimated by only 2%. The spatial distribution of the shaped
energy density is very similar to the fundamental eigenfunction, up to a cosine
distance of about 0.01. We obtain the energy density of transmission
eigenchannels inside the sample by numerical simulation of the scattering matrix.
Computing the transmission-averaged energy density over all transmission channels
yields the ensemble averaged energy density of shaped waves. From the averaged
energy density, we reconstruct its spatial distribution using the eigenfunctions
of the diffusion equation. The results of our study have exciting applications in
controlled biomedical imaging, efficient light harvesting in solar cells,
enhanced energy conversion in solid-state lighting, and low threshold random
lasers.
PMID- 27505817
TI - Quantification of the fluorescence sensing performance of microstructured optical
fibers compared to multi-mode fiber tips.
AB - Microstructured optical fibers, particularly those with a suspended-core
geometry, have frequently been argued as efficient evanescent-field fluorescence
based sensors. However, to date there has not been a systematic comparison
between such fibers and the more common geometry of a multi-mode fiber tip
sensor. In this paper we make a direct comparison between these two fiber sensor
geometries both theoretically and experimentally. Our results confirm that
suspended-core fibers provide a significant advantage in terms of total collected
fluorescence signal compared to multi-mode fibers using an equivalent
experimental configuration.
PMID- 27505818
TI - Discrete dispersion scanning as a simple method for broadband femtosecond pulse
characterization.
AB - A simple and easy to implement technique for femtosecond pulse characterization
is proposed and experimentally verified. It is based on the introduction of a
known amount of dispersion (by controlling the number of passes through
dispersive material) and subsequent recording of the spectral positions of second
harmonic peaks obtained in a non-linear crystal. Such dependence allows for
direct retrieval of the pulse spectral phase. The presented pulse
characterization method is beneficial especially for broadband pulses, where the
second harmonic spectrum exceeds the detection bandwidth of a single
spectrometer.
PMID- 27505819
TI - Sensitivity analysis of volume scattering phase functions.
AB - To solve the radiative transfer equation and relate inherent optical properties
(IOPs) to apparent optical properties (AOPs), knowledge of the volume scattering
phase function is required. Due to the difficulty of measuring the phase
function, it is frequently approximated. We explore the sensitivity of derived
AOPs to the phase function parameterization, and compare measured and modeled
values of both the AOPs and estimated phase functions using data from Monterey
Bay, California during an extreme "red tide" bloom event. Using in situ
measurements of absorption and attenuation coefficients, as well as two sets of
measurements of the volume scattering function (VSF), we compared output from the
Hydrolight radiative transfer model to direct measurements. We found that several
common assumptions used in parameterizing the radiative transfer model
consistently introduced overestimates of modeled versus measured remote-sensing
reflectance values. Phase functions from VSF data derived from measurements at
multiple wavelengths and a single scattering single angle significantly
overestimated reflectances when using the manufacturer-supplied corrections, but
were substantially improved using newly published corrections; phase functions
calculated from VSF measurements using three angles and three wavelengths and
processed using manufacture-supplied corrections were comparable, demonstrating
that reasonable predictions can be made using two commercially available
instruments. While other studies have reached similar conclusions, our work
extends the analysis to coastal waters dominated by an extreme algal bloom with
surface chlorophyll concentrations in excess of 100 mg m-3.
PMID- 27505820
TI - Low-bias current 10 Gbit/s direct modulation of GaInAsP/InP membrane DFB laser on
silicon.
AB - Low-power consumption directly-modulated lasers are a key device for on-chip
optical interconnection. We fabricated a GaInAsP/InP membrane DFB laser that
exhibited a low-threshold current of 0.21 mA and single-mode operation with a sub
mode suppression ratio of 47 dB at a bias current of 2 mA. A high modulation
efficiency of 11 GHz/mA1/2 was obtained. A 10 Gbit/s direct modulation
using a non-return-to-zero 231-1 pseudo-random bit sequence signal was
performed with a bias current of 1 mA, which is the lowest bias current ever
reported for direct modulation of a DFB laser. A bit-error rate of 10
9 was successfully achieved.
PMID- 27505821
TI - Topological description for gaps of one-dimensional symmetric all-dielectric
photonic crystals.
AB - We propose a topological description for gaps of one-dimensional symmetric all
dielectric photonic crystals (PCs). It is shown that, in the propagating
direction, the effective electromagnetic parameters of PCs can be derived from
one unit cell with mirror symmetry. Besides, at the frequencies of gaps, these
symmetric PCs can be described as photonic insulators with effective negative
permittivity or negative permeability. Moreover, based on the mapping of
Maxwell's equations to the Dirac equation and the band inversion achieved by
tuning the material and structural parameters, we demonstrate that the gaps of
PCs with effective negative permittivity or negative permeability possess
different topological orders. Lastly, we show that a bound state is robust
against the disorder under a zero-average-effective-mass condition in a
heterostructure made of two PCs with different topological orders.
PMID- 27505822
TI - Metal clad active fibres for power scaling and thermal management at kW power
levels.
AB - We present a new approach to high power fibre laser design, consisting of a
polymer-free all-glass optical fibre waveguide directly overclad with a high
thermal conductivity metal coating. This metal clad active fibre allows a
significant reduction in thermal resistance between the active fibre and the
laser heat-sink as well as a significant increase in the operating temperature
range. In this paper we show the results of a detailed thermal analysis of both
polymer and metal coated active fibres under thermal loads typical of kW fibre
laser systems. Through several different experiments we present the first
demonstration of a cladding pumped aluminium-coated fibre laser and the first
demonstration of efficient operation of a cladding-pumped fibre laser at
temperatures of greater than 400 degrees C. Finally, we highlight the
versatility of this approach through operation of a passively (radiatively)
cooled ytterbium fibre laser head at an output power of 405 W in a compact and
ultralight package weighing less than 100 g.
PMID- 27505823
TI - Design methodology for micro-discrete planar optics with minimum illumination
loss for an extended source.
AB - Recently, studies have examined techniques for modeling the light distribution of
light-emitting diodes (LEDs) for various applications owing to their low power
consumption, longevity, and light weight. The energy mapping technique, a design
method that matches the energy distributions of an LED light source and target
area, has been the focus of active research because of its design efficiency and
accuracy. However, these studies have not considered the effects of the emitting
area of the LED source. Therefore, there are limitations to the design accuracy
for small, high-power applications with a short distance between the light source
and optical system. A design method for compensating for the light distribution
of an extended source after the initial optics design based on a point source was
proposed to overcome such limits, but its time-consuming process and limited
design accuracy with multiple iterations raised the need for a new design method
that considers an extended source in the initial design stage. This study
proposed a method for designing discrete planar optics that controls the light
distribution and minimizes the optical loss with an extended source and verified
the proposed method experimentally. First, the extended source was modeled
theoretically, and a design method for discrete planar optics with the optimum
groove angle through energy mapping was proposed. To verify the design method,
design for the discrete planar optics was achieved for applications in
illumination for LED flash. In addition, discrete planar optics for LED
illuminance were designed and fabricated to create a uniform illuminance
distribution. Optical characterization of these structures showed that the design
was optimal; i.e., we plotted the optical losses as a function of the groove
angle, and found a clear minimum. Simulations and measurements showed that an
efficient optical design was achieved for an extended source.
PMID- 27505824
TI - Hyper-parallel Toffoli gate on three-photon system with two degrees of freedom
assisted by single-sided optical microcavities.
AB - Encoding qubits in multiple degrees of freedom (DOFs) of a quantum system allows
less-decoherence quantum information processing with much less quantum resources.
We present a compact and scalable quantum circuit to determinately implement a
hyper-parallel controlled-controlled-phase-flip (hyper-C2PF) gate in a
three-photon system in both the polarization and spatial DOFs. In contrast with
the one with many qubits encoding on one DOF only, our hyper-C2PF gate
operating two independent C2PF gates on a three-photon system with
less decoherence, and reduces the quantum resources required in quantum
information processing by a half. Additional photons, necessary for many
approaches, are not required in the present scheme. Our calculation shows that
this hyper-C2PF gate is feasible in experiment.
PMID- 27505825
TI - Intensity-only measurement of partially uncontrollable transmission matrix:
demonstration with wave-field shaping in a microwave cavity.
AB - Transmission matrices (TMs) have become a powerful and widely used tool to
describe and control wave propagation in complex media. In certain scenarios the
TM is partially uncontrollable, complicating its identification and use. In
standard optical wavefront shaping experiments, uncontrollable reflections or
imperfect illumination may be the cause; in reverberating cavities,
uncontrollable reflections off the walls have that effect. Here we employ phase
retrieval techniques to identify such a partially uncontrollable TM solely based
on random intensity-only reference measurements. We demonstrate the feasibility
of our method by focusing both on a single target as well as on multiple targets
in a microwave cavity, using a phase-binary Spatial-Microwave-Modulator.
PMID- 27505826
TI - Aperiodic Mo/Si multilayers for hard x-rays.
AB - In this work we have developed aperiodic Molybdenum/Silicon (Mo/Si) multilayers
(MLs) to reflect 16.25 keV photons at a grazing angle of incidence of 0.6 degrees
+/- 0.05 degrees . To the best of our knowledge this is the first time this
material system has been used to fabricate aperiodic MLs for hard x-rays. At
these energies new hurdles arise. First of all a large number of bilayers is
required to reach saturation. This poses a challenge from the manufacturing point
of view, as thickness control of each ML period becomes paramount. The latter is
not well defined a priori, due to the thickness of the interfacial silicide
layers which has been observed to vary as a function of Mo and Si thickness.
Additionally an amorphous-to-crystalline transition for Mo must be avoided in
order maintain reasonably low roughness at the interfaces. This transition is
well within the range of thicknesses pertinent to this study. Despite these
difficulties our data demonstrates that we achieved reasonably flat ML response
across the angular acceptance of +/- 0.05 degrees , with an experimentally
confirmed average reflectivity of 28%. Such a ML prescription is well suited for
applications in the field of hard x-ray imaging of highly diverging sources.
PMID- 27505827
TI - Unusual anti-thermal degradation of bismuth NIR luminescence in bismuth doped
lithium tantalum silicate laser glasses.
AB - For application of bismuth laser glasses in either fiber amplifier or laser,
their performance stability in long run should be understood especially in
extreme conditions. However, so far, there are few reports on it. Here, we found,
after the cycle experiments on heating and cooling, that the proper increase of
lithium content in lithium tantalum silicate laser glass can lead to unusual anti
thermal degradation of bismuth NIR luminescence, which completely differs from
the scenario in germanate glass. FTIR, 29Si MAS NMR spectra,
absorption and dynamic photoluminescence spectra are employed to unravel how this
happens. The results illustrate that it should be due to the decrease of
polymerization of silicate glass network, which in turn allows the regeneration
at 250 degrees C, and therefore, the content increase of bismuth NIR emission
centers. In the meanwhile, we noticed though Bi luminescence can be thermally
quenched its peak does not shift along with temperature, which seldom appears in
laser materials. The unique property might guarantee the unshift of Bi fiber
laser wavelength once such glass was made into fiber devices even as the
environmental temperature changes. The role of lithium is discussed in the
evolution of glass structures, the suppression of glass heterogeneity, and the
thermal stability of Bi luminescence, and it should be helpful to design
homogeneous silicate laser glass with outstanding thermal stability.
PMID- 27505828
TI - Tunable bandpass microwave photonic filter with ultrahigh stopband attenuation
and skirt selectivity.
AB - we propose and demonstrate a bandpass microwave photonic filter (MPF) with
ultrahigh stopband attenuation and skirt selectivity based on a simple signal
cancellation technique. By injecting two phase modulated signals located on
opposite sides of two resonant gain peaks of a Fabry-Perot semiconductor optical
amplifier (FP-SOA), two microwave frequency responses can be generated by the two
input signals, respectively. The two frequency responses will add together within
the passband but cancel each other out within the stopband, thus generating a MPF
with simultaneous ultrahigh stopband attenuation and skirt selectivity. In the
experiment the obtained MPF exhibits single passband in the range from 0 to 18
GHz and is tunable from 4 to 16 GHz by adjusting the laser wavelengths. During
the tuning process the maximum stopband attenuation is 76.3 dB and the minimum 30
dB to 3-dB bandwidth shape factor is 3.5.
PMID- 27505829
TI - Experimental comparison between speckle and grating-based imaging technique using
synchrotron radiation X-rays.
AB - X-ray phase contrast and dark-field imaging techniques provide important and
complementary information that is inaccessible to the conventional absorption
contrast imaging. Both grating-based imaging (GBI) and speckle-based imaging
(SBI) are able to retrieve multi-modal images using synchrotron as well as lab
based sources. However, no systematic comparison has been made between the two
techniques so far. We present an experimental comparison between GBI and SBI
techniques with synchrotron radiation X-ray source. Apart from the simple
experimental setup, we find SBI does not suffer from the issue of phase
unwrapping, which can often be problematic for GBI. In addition, SBI is also
superior to GBI since two orthogonal differential phase gradients can be
simultaneously extracted by one dimensional scan. The GBI has less stringent
requirements for detector pixel size and transverse coherence length when a
second or third grating can be used. This study provides the reference for
choosing the most suitable technique for diverse imaging applications at
synchrotron facility.
PMID- 27505830
TI - Ultrathin zoom telescopic objective.
AB - We report an ultrathin zoom telescopic objective that can achieve continuous zoom
change and has reduced compact volume. The objective consists of an annular
folded lens and three electrowetting liquid lenses. The annular folded lens
undertakes the main part of the focal power of the lens system. Due to a multiple
fold design, the optical path is folded in a lens with the thickness of ~1.98mm.
The electrowetting liquid lenses constitute a zoom part. Based on the proposed
objective, an ultrathin zoom telescopic camera is demonstrated. We analyze the
properties of the proposed objective. The aperture of the proposed objective is
~15mm. The total length of the system is ~18mm with a tunable focal length ~48mm
to ~65mm. Compared with the conventional zoom telescopic objective, the total
length has been largely reduced.
PMID- 27505831
TI - Frequency modulation of high-order harmonic generation in an orthogonally
polarized two-color laser field.
AB - We have experimentally investigated the frequency modulation of high-order
harmonics in an orthogonally polarized two-color laser field consisting of a mid
infrared 1800nm fundamental pulse and its second harmonic pulse. It is
demonstrated that the high harmonic spectra can be fine-tuned as we slightly
change the relative delay of the two-color laser pulses. By analyzing the
relative frequency shift of each harmonic at different two-color delays, the
nonadiabatic spectral shift induced by the rapid variation of the intensity
dependent intrinsic dipole phase can be distinguished from the blueshift induced
by the change of the refractive index during self-phase modulation (SPM). Our
comprehensive analysis shows that the frequency modulation pattern is a
reflection of the average emission time of high-order harmonic generation (HHG),
thus offering a simple method to fine-tune the spectra of the harmonics on a sub
cycle time scale.
PMID- 27505832
TI - Two-frame phase-shifting interferometry for testing optical surfaces.
AB - Standard phase-shifting interferometry (PSI) generally requires collecting at
least three phase-shifted interferograms to extract the physical quantity being
measured. Here, we propose the application of a simple two-frame PSI for the
testing of a range of optical surfaces, including flats, spheres, and aspheres.
The two-frame PSI extracts modulated phase from two randomly phase-shifted
interferograms using a Gram-Schmidt algorithm, and can work in either null
testing or non-null testing modes. Since only two interferograms are used for
phase demodulation and the phase shift amount can be random, requirements on
environmental conditions and phase shifter calibration are greatly relaxed.
Experimental results of three different mirrors suggest that the two-frame PSI
can achieve comparable measurement precision with conventional multi-frame PSI,
but has faster data acquisition speed and less stringent hardware requirements.
The proposed two-frame PSI expands the flexibility of PSI and holds great
potential in many applications.
PMID- 27505833
TI - Fabrication of europium-doped silica optical fiber with high Verdet constant.
AB - A europium-doped (Eu-doped) silica optical fiber is fabricated using modified
chemical vapor deposition (MCVD) technology. Europium fluoride (EuF3)
material is introduced into the fiber core with a high temperature vaporizing
technique. Its concentration is approximately 0.11 at %. The outer and core
diameters of doped fiber are approximately 122 and 9 MUm, respectively.
Refractive index difference (RID) between core and cladding is approximately 2%.
A magneto-optical effect measurement system, which is based on the Stokes
polarization parameters method, is set up to analyze its magneto-optical
properties. The Verdet constant of the Eu-doped optical fiber is -4.563 rad
T-1m-1, which is approximately double than that of single
mode fiber (SMF) at 660 nm.
PMID- 27505834
TI - Group velocity locked vector dissipative solitons in a high repetition rate fiber
laser.
AB - Vectorial nature of dissipative solitons (DSs) with high repetition rate is
studied for the first time in a normal-dispersion fiber laser. Despite the fact
that the formed DSs are strongly chirped and the repetition rate is greater than
100 MHz, polarization locked and polarization rotating group velocity locked
vector DSs can be formed under 129.3 MHz fundamental mode-locking and 258.6 MHz
harmonic mode-locking of the fiber laser, respectively. The two orthogonally
polarized components of these vector DSs possess distinctly different central
wavelengths and travel together at the same group velocity in the laser cavity,
resulting in a gradual spectral edge and small steps on the optical spectrum,
which can be considered as an auxiliary indicator of the group velocity locked
vector DSs. Moreover, numerical simulations well confirm the experimental
observations and further reveal the impact of the net cavity birefringence on the
properties of the formed vector DSs.
PMID- 27505835
TI - Mode structure of planar optical antennas on dielectric substrates.
AB - We report a numerical study, supported by photoemission electron microscopy
(PEEM), of sub-micron planar optical antennas on transparent substrate. We find
these antennas generate intricate near-field spatial field distributions with odd
and even numbers of nodes. We show that the field distributions are primarily
superpositions of planar surface plasmon polariton modes confined to the
metal/substrate interface. The mode structure provides opportunities for coherent
switching and optical control in sub-micron volumes.
PMID- 27505836
TI - Free-space to few-mode-fiber coupling under atmospheric turbulence.
AB - High speed free space optical communication (FSOC) has taken advantages of
components developed for fiber-optic communication systems. Recently, with the
rapid development of few-mode-fiber based fiber communication systems, few-mode
fiber components might further promote their applications in FSOC system. The
coupling efficiency between free space optical beam and few-mode fibers under
atmospheric turbulence effect are investigated in this paper. Both simulation and
experimental results show that, compared with single-mode fiber, the coupling
efficiencies for a 2-mode fiber and a 4-mode fiber are improved by ~4 dB and ~7
dB respectively in the presence of medium moderate and strong turbulence.
Compared with single-mode fiber, the relative standard deviation of received
power is restrained by 51% and 66% respectively with a 4-mode and 2-mode fiber.
PMID- 27505837
TI - Ptychographic hyperspectral spectromicroscopy with an extreme ultraviolet high
harmonic comb.
AB - We report a proof-of-principle demonstration of a new scheme of spectromicroscopy
in the extreme ultraviolet (EUV) spectral range, where the spectral response of
the sample at different wavelengths is imaged simultaneously. This scheme is
enabled by combining ptychographic information multiplexing (PIM) with a tabletop
EUV source based on high harmonic generation, where four spectrally narrow
harmonics near 30 nm form a spectral comb structure. Extending PIM from
previously demonstrated visible wavelengths to the EUV/X-ray wavelengths promises
much higher spatial resolution and a more powerful spectral contrast mechanism,
making PIM an attractive spectromicroscopy method in both microscopy and
spectroscopy aspects. In addition to spectromicroscopy, this method images the
multicolor EUV beam in situ, making this a powerful beam characterization
technique. In contrast to other methods, the techniques described here use no
hardware to separate wavelengths, leading to efficient use of the EUV radiation.
PMID- 27505838
TI - Generation of Q-switched mode locking controlled rectangular noise-like soliton
bunching in a Tm-doped fiber laser.
AB - We report on an interesting phenomenon of the combination of Q-switched mode
locked pulses (QSMLP) and rectangular noise-like pulses (RNLP) as a unit in a Tm
doped ring fiber laser which contains a Fabry-Perot (F-P) subcavity based on the
nonlinear polarization evolution (NPE) technique. The RNLP and QSMLP are
independently generated in the ring cavity and F-P subcavity, respectively. A
notable characteristic is that the physical parameters of RNLP, e.g. repetition
rate and pulse duration, are controlled by QSMLP. Thus, they form as a composite
bunching, which is termed as "Q-switched mode locking controlled rectangular
noise-like soliton bunching (QRNSB)". Further investigation shows that the
existence of QRNSB only occurs in high pumping conditions, while both fundamental
mode-locking pulses and the coexistence of QSMLP and solitons are achieved in low
pumping ones. Our work can enrich the understanding of the nonlinear dynamics in
fiber lasers.
PMID- 27505839
TI - Scalar-vector soliton fiber laser mode-locked by nonlinear polarization rotation.
AB - We report a passively mode-locked fiber laser by nonlinear polarization rotation
(NPR), where both vector and scalar soliton can co-exist within the laser cavity.
The mode-locked pulse evolves as a vector soliton in the strong birefringent
segment and is transformed into a regular scalar soliton after the polarizer
within the laser cavity. The existence of solutions in a polarization-dependent
cavity comprising a periodic combination of two distinct nonlinear waves is first
demonstrated and likely to be applicable to various other nonlinear systems. For
very large local birefringence, our laser approaches the operation regime of
vector soliton lasers, while it approaches scalar soliton fiber lasers under the
condition of very small birefringence.
PMID- 27505840
TI - Scalable screen-size enlargement by multi-channel viewing-zone scanning
holography.
AB - Viewing-zone scanning holographic displays can enlarge both the screen size and
the viewing zone. However, limitations exist in the screen size enlargement
process even if the viewing zone is effectively enlarged. This study proposes a
multi-channel viewing-zone scanning holographic display comprising multiple
projection systems and a planar scanner to enable the scalable enlargement of the
screen size. Each projection system produces an enlarged image of the screen of a
MEMS spatial light modulator. The multiple enlarged images produced by the
multiple projection systems are seamlessly tiled on the planar scanner. This
screen size enlargement process reduces the viewing zones of the projection
systems, which are horizontally scanned by the planar scanner comprising a
rotating off-axis lens and a vertical diffuser to enlarge the viewing zone. A
screen size of 7.4 in. and a viewing-zone angle of 43.0 degrees are
demonstrated.
PMID- 27505841
TI - Experimental verification of epsilon-near-zero plasmon polariton modes in
degenerately doped semiconductor nanolayers.
AB - We investigate optical polariton modes supported by subwavelength-thick
degenerately doped semiconductor nanolayers (e.g. indium tin oxide) on glass in
the epsilon-near-zero (ENZ) regime. The dispersions of the radiative (R, on the
left of the light line) and non-radiative (NR, on the right of the light line)
ENZ polariton modes are experimentally measured and theoretically analyzed
through the transfer matrix method and the complex-frequency/real-wavenumber
analysis, which are in remarkable agreement. We observe directional near-perfect
absorption using the Kretschmann geometry for incidence conditions close to the
NR-ENZ polariton mode dispersion. Along with field enhancement, this provides us
with an unexplored pathway to enhance nonlinear optical processes and to open up
directions for ultrafast, tunable thermal emission.
PMID- 27505842
TI - Spatial optical phase-modulating metadevice with subwavelength pixelation.
AB - Dynamic control over optical wavefronts enables focusing, diffraction and
redirection of light on demand, however, sub-wavelength resolution is required to
avoid unwanted diffracted beams that are present in commercial spatial light
modulators. Here we propose a realistic metadevice that dynamically controls the
optical phase of reflected beams with sub-wavelength pixelation in one dimension.
Based on reconfigurable metamaterials and nanomembrane technology, it consists of
individually moveable metallic nanowire actuators that control the phase of
reflected light by modulating the optical path length. We demonstrate that the
metadevice can provide on-demand optical wavefront shaping functionalities of
diffraction gratings, beam splitters, phase-gradient metasurfaces, cylindrical
mirrors and mirror arrays - with variable focal distance and numerical aperture -
without unwanted diffraction.
PMID- 27505843
TI - Room temperature continuous wave operation of InAs-based quantum cascade lasers
at 15 um.
AB - We report low threshold InAs/AlSb quantum cascade lasers emitting near 15 um. The
devices are based on a vertical design similar to those employed previously in
far infrared InAs-based QCLs, whereas the doping level of the active core is
considerably decreased. The lasers exhibit a threshold current density as low as
730 A/cm2 in pulsed mode at room temperature and can operate in this
regime up to 410K. The continuous wave regime of operation has been achieved in
these devices at temperatures up to 20 degrees C. The cw regime is demonstrated
for InAs-based QCLs for the first time at room temperature.
PMID- 27505844
TI - Differential refractive index sensor based on photonic molecules and defect
cavities.
AB - We present a novel differential refractive index sensor prototype based on a
matrix of photonic molecules (PM) of soda-lime glass cylinders
(epsilonc = 4.5) and two defect cavities. The measured and simulated
spectra in the microwave range (8-12 GHz) show a wide photonic stop band with two
localized states: the reference state, bound to a decagonal ring of cylinders and
the sensing state, bound to the defect cavities. The defect mode is very
sensitive to the permittivity of the material inserted in the cavity while the
state in the PM remains unperturbed. We find that the response of the sensor is
linear. These results can be extrapolated to the visible range due to scale
invariance of Maxwell equations.
PMID- 27505845
TI - Evaluation of endometrial natural killer cell expression of CD4, CD103, and CD16
cells in women with unexplained infertility.
AB - OBJECTIVE: To determine whether natural killer cell (NK) concentrations in the
mid-secretory endometrial tissue of women with unexplained infertility differ
from those in the mid-secretory endometrial tissue of fertile women. METHODS:
This study was conducted with 22 patients with unexplained infertility caused by
unsuccessful ovulation induced with gonadotrophins and 12 healthy fertile women,
who formed a control group. Mid-secretory endometrial tissue samples were
obtained with a Pipelle catheter, and the endometrial NK cell phenotypes were
determined by flow cytometry. RESULTS: The median number of CD4+ cells in the
endometrium was significantly lower in women with unexplained infertility
compared with in the fertile controls (3.31 vs. 5.81; p=0.02). The CD4(+)/CD8(+)
cell ratio in the unexplained-infertility group was significantly lower than that
in the control group (0.42 vs. 0.76, p=0.01). The median number of CD103(+) cells
in the endometrium of the infertile group was significantly lower than that in
the endometrium of the control group (4.40 vs. 6.73, p=0.02). The median number
of CD16(+) cells was significantly higher in infertile women than in control
women (0.12 vs. 0.001, p=0.01). CONCLUSIONS: Significant reductions in the
numbers of CD4(+) and CD103(+) cells as well as in the CD4(+)/CD8(+) ratio but an
increased number of CD16(+) cells in the endometrium of infertile women suggest
that disordered NK cell activity may be a contributor to the etiology of
unexplained infertility.
PMID- 27505846
TI - Distribution of HLA DRB1 and DQB1 alleles and DRB1-DQB1 haplotypes among Bahraini
women with polycystic ovary syndrome.
AB - OBJECTIVE: This study investigated the association between HLA-DRB1 and -DQB1
alleles and DRB1-DQB1 haplotypes, and polycystic ovary syndrome (PCOS) in
Bahraini women. DESIGN: Case-control, retrospective study. METHODS: Study
subjects comprised 80 women with PCOS, and 169 age- and ethnically-matched
control women. DRB1 and DQB1 genotyping was done by PCR-SSP. RESULTS: Of the 13
DRB1 alleles and 5 DQB1 alleles identified, DRB1*10 (14.3% vs. 4.4%) and DRB1*14
(8.7% vs. 1.1%), along with DQB1*05 (35.0% vs. 23.9%), were the most frequent
alleles in cases, while DRB1*11 (15.3% vs. 6.8%) was the frequent allele found in
controls. The association of PCOS with DRB1*10 (Pc<0.001), DRB1*14 (Pc<0.001),
DQB1*05 (Pc=0.040), but not DRB1*11 (Pc=0.076) persisted after correcting for
multiple comparisons. DRB1-DQB1 haplotype analysis identified nine common shared
haplotypes in women with PCOS and control women, with a frequency exceeding 1%.
Significantly higher frequency of DRB1*10-DQB1*05 (12.4% vs. 3.1%) and DRB1*14
DQB1*03 (5.6% vs. 1.0%), and reduced frequency of DRB1*11-DQB1*03 (4.1% vs.
14.1%) haplotypes were seen in women with PCOS vs. control women, thus assigning
PCOS-susceptible and -protective nature to these haplotypes, respectively. This
association persisted after controlling for multiple comparisons. CONCLUSION: Our
results confirm an association of HLA-DRB1 and -DQB1 alleles and haplotypes with
PCOS susceptibility in Bahraini Arabs, further underscoring the
immunological/inflammatory nature of this disorder.
PMID- 27505847
TI - Lysophosphatidic acid-induced RhoA signaling and prolonged macrophage
infiltration worsens fibrosis and fatty infiltration following rotator cuff
tears.
AB - Previous studies have suggested that macrophage-mediated chronic inflammation is
involved in the development of rotator cuff muscle atrophy and degeneration
following massive tendon tears. Increased RhoA signaling has been reported in
chronic muscle degeneration, such as muscular dystrophy. However, the role of
RhoA signaling in macrophage infiltration and rotator muscle degeneration remains
unknown. Using a previously established rat model of massive rotator cuff tears,
we found RhoA signaling is upregulated in rotator cuff muscle following a massive
tendon-nerve injury. This increase in RhoA expression is greatly potentiated by
the administration of a potent RhoA activator, lysophosphatidic acid (LPA), and
is accompanied by increased TNFalpha and TGF-beta1 expression in rotator cuff
muscle. Boosting RhoA signaling with LPA significantly worsened rotator cuff
muscle atrophy, fibrosis, and fatty infiltration, accompanied with massive
monocytic infiltration of rotator cuff muscles. Co-staining of RhoA and the
tissue macrophage marker CD68 showed that CD68+ tissue macrophages are the
dominant cell source of increased RhoA signaling in rotator cuff muscles after
tendon tears. Taken together, our findings suggest that LPA-mediated RhoA
signaling in injured muscle worsens the outcomes of atrophy, fibrosis, and fatty
infiltration by increasing macrophage infiltraion in rotator cuff muscle.
Clinically, inhibiting RhoA signaling may represent a future direction for
developing new treatments to improve muscle quality following massive rotator
cuff tears. (c) 2016 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res 35:1539-1547, 2017.
PMID- 27505848
TI - Synthesis and Antileukemic Activities of Piperlongumine and HDAC Inhibitor
Hybrids against Acute Myeloid Leukemia Cells.
AB - Synergistic-to-additive antileukemic interactions of piperlongumine (PL) and HDAC
inhibitor (HDACi) SAHA (Vorinostat) provide a compelling rationale to construct
PL-HDACi hybrids, such as 1-58, which recapitulated the synergism between the
parental compounds in high-risk and chemoresistant AML cells. Both PL and HDACi
components, either in combination or in hybrid molecules, are essential for
inducing significant DNA damage and apoptosis. Introducing C2-chloro substituent
to 1-58 yielded 3-35 with increased cytotoxicity but decreased selectivity in
noncancerous MCF-10A cells; eliminating C7-C8 olefin of PL obtained 3-31/3-98
scaffolds which were still more active than PL or SAHA in AML and were well
tolerated by MCF-10A cells. The HDACi function was crucial for modulating
expression of DNA repair and apoptosis-related proteins. Collectively, PL and
SAHA hybrids are potent, multifunctional anti-AML agents, acting in part, by
interfering cellular GSH defense, suppressing expression of DNA repair and pro
survival proteins, and inducing expression of pro-apoptotic proteins.
PMID- 27505849
TI - [Not Available].
PMID- 27505850
TI - [Not Available].
PMID- 27505851
TI - [Not Available].
AB - Bee and wasp stings can cause allergic reactions. Although the local reactions
are more frequent, anaphylaxis due to insect stings can be potentially fatal.
Rapid recognition of anaphylaxis is therefore critical and reactions should
immediately be treated with i.m. adrenaline. Patients having experienced
anaphylaxis should be referred to an allergist for diagnostic evaluation and
possible venom-immunotherapy (VIT). The clinical history is essential in
diagnosis of venom allergy as the test results are not always reliable.
Diagnostic testing with venom components might be beneficial in appropriate
patients. The analysis of serum tryptase from the acute episode can be crucial.
Mastocytosis is associated in about 8 percent of patients with severe anaphylaxis
from insect stings and should be considered in the differential diagnosis. VIT is
indicated for patients with a history of anaphylaxis and is effective in
preventing future anaphylaxis from Hymenoptera stings.
PMID- 27505852
TI - [Not Available].
PMID- 27505853
TI - [Not Available].
PMID- 27505854
TI - N-pentyl-nitrofurantoin induces apoptosis in HL-60 leukemia cell line by
upregulating BAX and downregulating BCL-xL gene expression.
AB - BACKGROUND: Nitrofurantoin is a nitroderivative antibiotic that has bactericidal
activity against pathogens causing urinary tract infection. A few studies have
reported that nitrofurantoin has cytotoxic activity against cancer cells;
however, nitrofurans remain a poorly explored class of compounds with respect to
their anticancer potential. The aim of this study was to investigate the
anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP),
on HL-60 leukemia cells. METHODS: Cytotoxicity was assayed by the MTT assay. Cell
morphology and phosphatidylserine externalization were visualized after Giemsa
May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial
depolarization were measured by flow cytometry. BAX and BCL-xL expression was
examined by RT-PCR. RESULTS: NFP was 3.8-fold more cytotoxic against HL-60
leukemia cells than against normal cells. NFP reduced the number of viable cells
24h after the treatment with a concomitant increase in the number of apoptotic
cells indicated by the externalization of phosphatidylserine, DNA fragmentation,
and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the
mRNA levels of BCL-xL decreased. CONCLUSION: The results indicate that NFP
induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.
PMID- 27505855
TI - Puerarin inhibits the inflammatory response in atherosclerosis via modulation of
the NF-kappaB pathway in a rabbit model.
AB - BACKGROUND: The isoflavone puerarin [7-hydroxy-3-(4-hydroxyphenyl)-1-benzopyran-4
one 8-(beta-D-glucopyranoside)] possesses many biological activities. In this
study, we investigated the effects of puerarin on adhesion molecules (AMs),
including serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular
cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1
(E-selectin), and the activation of nuclear factor kappa B (NF-kappaB) in rabbits
with experimental atherosclerosis. METHODS: In total, 24 rabbits were divided
into control (standard diet), high-lipid diet (HLD), and PUE (HLD supplemented
with puerarin) groups. At the end of weeks 0, 8, and 16, serum levels of AMs were
measured. At the end of week 16, the thickness of the intima was detected.
Protein and mRNA levels of AMs were checked by immunohistochemistry and RT-PCR,
respectively. Protein levels of p65 NF-kappaB and phosphorylation of inhibitor
kappaB (I-kappaB) were investigated by Western blotting. RESULTS: Atherosclerotic
lesions in the thoracic arch were found in the HLD and PUE groups, but not in the
control group. Compared with the HLD group, the thickness of the intima in the
PUE group was reduced. Our results indicate that puerarin reduced the protein and
mRNA levels of AMs in this rabbit model. We also found that the reduced AM levels
were due to inhibition of the phosphorylation and degradation of I-kappaB,
resulting in reduced p65 NF-kappaB nuclear translocation. CONCLUSIONS: This study
indicates that the effect of puerarin on the suppression of atherosclerosis was
connected with an inhibited inflammatory response and reduced NF-kappaB
activation.
PMID- 27505856
TI - Evaluation of the Substrate Scope of Benzoic Acid (De)carboxylases According to
Chemical and Biochemical Parameters.
AB - The enzymatic carboxylation of phenolic compounds has been attracting increasing
interest in recent years, owing to its regioselectivity and technical potential
as a biocatalytic equivalent for the Kolbe-Schmitt reaction. Mechanistically the
reaction was demonstrated to occur through electrophilic aromatic
substitution/water elimination with bicarbonate as a cosubstrate. The effects of
the substituents on the phenolic ring have not yet been elucidated in detail, but
this would give detailed insight into the substrate-activity relationship and
would provide predictability for the acceptance of future substrates. In this
report we show how the kinetic and (apparent) thermodynamic behavior can be
explained through the evaluation of linear free energy relationships based on
electronic, steric, and geometric parameters and through the consideration of
enzyme-ligand interactions. Moreover, the similarity between the benzoic acid
decarboxylases and the amidohydrolases superfamily is investigated, and
promiscuous hydrolytic activity of the decarboxylase in the context of the
hydrolysis of an activated ester bond has been established.
PMID- 27505857
TI - Impact of renal transplantation on glucose tolerance in Japanese recipients with
impaired glucose tolerance.
AB - AIMS: To investigate changes in glucose tolerance, insulin secretion and insulin
sensitivity in Japanese recipients before and 1 year after renal transplantation.
METHODS: We conducted a study of Japanese recipients without diabetes who
underwent renal transplantation at Hokkaido University Hospital. A 75-g oral
glucose tolerance test was performed before and 1 year after renal
transplantation in these recipients. Insulin sensitivity was estimated using the
Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR).
Insulin secretion was evaluated based on the insulin secretion sensitivity index
2 (ISSI-2). RESULTS: Of the 62 renal transplant recipients, 31 were diagnosed as
having impaired glucose tolerance before transplantation. Among these 31
recipients, after 1 year, four had developed new-onset diabetes after
transplantation, and nine had impaired glucose tolerance. Unexpectedly, 18
changed from impaired to normal glucose tolerance. When these recipients with
impaired glucose tolerance were classified into a non-amelioration group and an
amelioration group, the ISSI-2 was significantly reduced, with no significant
changes in the Matsuda index or HOMA-IR, in the non-amelioration group 1 year
after renal transplantation. By contrast, ISSI-2 and Matsuda index values were
significantly increased, with no significant changes in HOMA-IR values in the
amelioration group. CONCLUSIONS: More than half of Japanese renal transplant
recipients with impaired glucose tolerance had normal glucose tolerance 1 year
after renal transplantation. These results suggest that an increase in insulin
secretion and whole insulin sensitivity was associated with improvement in
glucose tolerance in these recipients.
PMID- 27505858
TI - The use of Zymosan A and bacteria anchored to tumor cells for effective cancer
immunotherapy: B16-F10 murine melanoma model.
AB - The idea of using killed microorganisms or their parts for a stimulation of
immunity in the cancer immunotherapy is very old, but the question of
interactions and binding of these preparations to tumor cells has not been
addressed so far. The attachment of Zymosan A and both Gram-positive and Gram
negative bacteria to tumor cells was tested in in vivo experiments. This binding
was accomplished by charge interactions, anchoring based on hydrophobic chains
and covalent bonds and proved to be crucial for a strong immunotherapeutic
effect. The establishment of conditions for simultaneous stimulation of both Toll
like and phagocytic receptors led to very strong synergy. It resulted in tumor
shrinkage and its temporary or permanent elimination. The role of neutrophils in
cancer immunotherapy was demonstrated and the mechanism of their action
(frustrated phagocytosis) was proposed. Finally, therapeutic approaches
applicable for safe human cancer immunotherapy are discussed. Heat killed
Mycobacterium tuberculosis covalently attached to tumor cells seems to be
promising tool for this therapy.
PMID- 27505859
TI - A Comprehensive Study of Copper Guanidine Quinoline Complexes: Predicting the
Activity of Catalysts in ATRP with DFT.
AB - Copper complexes of the hybrid guanidine ligands 1,3-dimethyl-N-(quinolin-8-yl)
imidazolidin-2-imine (DMEGqu) and 1,1,3,3-tetramethyl-2-(quinolin-8-yl)-guanidine
(TMGqu) have been studied comprehensively with regard to their structural and
electrochemical properties and their activity in atom transfer radical
polymerization (ATRP). A simple analysis of the molecular structures of the
complexes gives no indication about their activity in ATRP; however, with the
help of DFT and NBO analysis the influence of particular coordinating donors on
the electrochemical properties could be fully elucidated. With an adequate DFT
methodology and newly applied theoretical isodesmic reactions it was possible to
predict the relative position of the redox potentials of copper complexes
containing DMEGqu and TMGqu ligands. In addition, predictions could be made as to
whether the complexes of DMEGqu or TMGqu are more active in ATRP. Four new Cu(I)
complexes were tested in standard ATRP reactions and kinetically investigated
both in bulk and in solution. It could be proven that complexes featuring DMEGqu
possess a lower redox potential and are more active in ATRP, although the
tetramethylguanidine moiety represents the stronger donor.
PMID- 27505860
TI - Slip length measurement of gas flow.
AB - In this paper, we present a review of the most important techniques used to
measure the slip length of gas flow on isothermal surfaces. First, we present the
famous Millikan experiment and then the rotating cylinder and spinning rotor
gauge methods. Then, we describe the gas flow rate experiment, which is the most
widely used technique to probe a confined gas and measure the slip. Finally, we
present a promising technique using an atomic force microscope introduced
recently to study the behavior of nanoscale confined gas.
PMID- 27505862
TI - MiR-139-3p induces cell apoptosis and inhibits metastasis of cervical cancer by
targeting NOB1.
AB - MicroRNAs (miRNAs) play an important role in the development of various cancers,
including cervical cancer (CC). The dysregulation of miRNA expression is
associated with oncogenic transformation and miRNA often act as tumor
suppressors. In this study, we aimed to analyze the effect on and mechanism of
miR-139-3p in the progression of CC. The result of real-time PCR showed that miR
139-3p was down-regulated in CC tissues and cell lines. Overexpression of miR-139
3p significantly suppressed HeLa cell proliferation, migration and invasion and
induced cell apoptosis. Bioinformatics analysis and luciferase reporter gene
assay confirmed that NOB1 was targeted by miR-139-3p at the 3'-untranslated
region (3'UTR) of its mRNA sequence. Furthermore, overexpression of NOB1
counteracted the effects of miR-139-3p suppression. Our results suggest that miR
139-3p may act as a tumor suppressor that can inhibit CC cell proliferation,
migration and invasion and induce cell apoptosis through down-regulation of NOB1
expression. Taken together, this study provides a novel potential therapeutic
strategy for the treatment of CC.
PMID- 27505861
TI - 4-Biphenylalanine- and 3-Phenyltyrosine-Derived Hydroxamic Acids as Inhibitors of
the JumonjiC-Domain-Containing Histone Demethylase KDM4A.
AB - Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and
H3K36 methylation states, has been related to the pathology of several human
cancers. We found that a previously reported hydroxamate-based histone
deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this
demethylase with an IC50 value of 25.4 MUm. Herein we report the synthesis and
biochemical evaluations, with two orthogonal in vitro assays, of a series of
derivatives of this lead structure. With extensive chemical modifications on the
lead structure, also by exploiting the versatility of the radical arylation with
aryldiazonium salts, we were able to increase the potency of the derivatives
against KDM4A to the low-micromolar range and, more importantly, to obtain
demethylase selectivity with respect to HDACs. Cell-permeable derivatives clearly
showed a demethylase-inhibition-dependent antiproliferative effect against HL-60
human promyelocytic leukemia cells.
PMID- 27505863
TI - Genetic and functional analyses do not explain the association of high PRC1
expression with poor survival of breast carcinoma patients.
AB - Microtubules are vitally important for eukaryotic cell division. Therefore, we
evaluated the relevance of mitotic kinesin KIF14, protein-regulating cytokinesis
1 (PRC1), and citron kinase (CIT) for the prognosis of breast carcinoma patients.
Transcript levels were assessed by quantitative real-time PCR in tissues from two
independent groups of breast carcinoma patients and compared with clinical data.
Tissue PRC1 protein levels were estimated using immunoblotting, and the PRC1
tagged haplotype was analyzed in genomic DNA. A functional study was performed in
MDA-MB-231 cells in vitro. KIF14, PRC1, and CIT transcripts were overexpressed in
tumors compared with control tissues. Tumors without expression of hormonal
receptors or high-grade tumors expressed significantly higher KIF14 and PRC1
levels than hormonally-positive or low-grade tumors. Patients with high intra
tumoral PRC1 levels had significantly worse disease-free survival than patients
with low levels. PRC1 rs10520699 and rs11852999 polymorphisms were associated
with PRC1 transcript levels, but not with patients survival. Paclitaxel-induced
PRC1 expression, but PRC1 knockdown did not modify the paclitaxel cytotoxicity in
vitro. PRC1 overexpression predicts poor disease-free survival of patients with
breast carcinomas. Genetic variability of PRC1 and the protein interaction with
paclitaxel cytotoxicity do not explain this association.
PMID- 27505864
TI - Antidiabetic assessment; in vivo study of gold and core-shell silver-gold
nanoparticles on streptozotocin-induced diabetic rats.
AB - Recently, we have published a pioneering work on green biosynthesis and complete
characterization of gold and core shell silver-gold nanoparticles (AuNPs and
Ag@AuNPs). Herein, the so obtained nanoparticles are assessed for their
antidiabetic activity in streptozotocin-induced diabetic rats. Thus, sixty-four
male albino rats were divided into eight groups: control untreated; diabetic
rats; diabetic rats received standard drug; diabetic rats received carrier only;
diabetic rats received 0.5ml AuNPs; diabetic rats received 1ml AuNPs; diabetic
rats received 0.5ml Ag@AuNPs and diabetic rats received 1ml Ag@AuNPs for twenty
one days. Results revealed that diabetic rats treated with AuNPs or Ag@AuNPs
restored normal glucose level. In particular, Ag@AuNPs was found to significantly
induce a reduction in blood glucose and restore both the high serum insulin level
and glucokinase activity compared to the control normal rats. The results
obtained disclose the effectual role of Ag@AuNPs in reducing the lipid profile,
an anti-inflammatory effect in diabetic rats assessed using inflammatory markers
IL-alpha and C-reactive protein (CRP). Histopathological examination of diabetic
rats signifies distortion in the arrangement of cells around the central vein,
inflammatory cells, pyknotic and apoptotic nuclei. Kidney of diabetic rat appears
with vacuolation and pyknotic nuclei of some tubules. On the other hand, the
liver of diabetic rat treated with Ag@AuNPs displayed normal hepatic cells with
only few necrosis of hepatocytes. Ag@AuNPs restored the increased number of
caspase-3 stained cells in the liver and kidney tissue in diabetic rats. In
conclusion, Ag@AuNPs was observed to improve diabetic condition by limiting
prolonged inflammation, suppressing oxidative stress and elevating the
antioxidant defense system in diabetic rats which subsequently evoke the
potential impact of AuNPs as a cost effective therapeutic cure in diabetic
treatments and its complications.
PMID- 27505865
TI - When the woman gets violent: the construction of domestic abuse experience from
heterosexual men's perspective.
AB - AIMS AND OBJECTIVES: To promote a critical approach on the conceptualisation of
domestic violence by investigating the experience of abuse on the part of men who
are victims of domestic violence by their female partners. BACKGROUND: Media
attention and prevention programmes relating to domestic violence have mainly
focused on women as the victims and men as the perpetrators. The underlying idea
is that violence is predominantly physical and a prerogative of men. This
conceptualisation of violence reduces the opportunities for the consideration of
different modalities of abuse. DESIGN: Discourse analysis within a qualitative
approach. METHODS: Semistructured interviews with 20 Italian men who claimed to
have been abused by their female partners were conducted via Skype and analysed
with the software atlas.ti. The grounded theory methodology was used to avoid
imposing external points of view. Personal data were collected; in particular,
their occupational level was compared to their partners' to assess the social
power within the couple. RESULTS: Because of their strong endorsement of social
and cultural values, participants showed a protective attitude towards their
partners and imputed their violent acts to fragility or an external condition.
Emotional distress emerged due to the isolation and subsequent inability to seek
help. Although the physical violence reported is severe, the psychological
violence was indicated as more damaging. CONCLUSION: Gaining an understanding of
how men experience domestic abuse offers an opportunity to provide better
prevention and intervention for them and other family members at risk of abuse.
RELEVANCE TO CLINICAL PRACTICE: The study identifies gaps in service provision
generated by a lack of information or perceived prejudice towards abused men. The
role of the nurse in supporting male victims is discussed, and future
applications for treatments and prevention plans are proposed.
PMID- 27505866
TI - Natural Constraints to Species Diversification.
AB - Identifying modes of species diversification is fundamental to our understanding
of how biodiversity changes over evolutionary time. Diversification modes are
captured in species phylogenies, but characterizing the landscape of
diversification has been limited by the analytical tools available for directly
comparing phylogenetic trees of groups of organisms. Here, we use a novel, non
parametric approach and 214 family-level phylogenies of vertebrates representing
over 500 million years of evolution to identify major diversification modes, to
characterize phylogenetic space, and to evaluate the bounds and central
tendencies of species diversification. We identify five principal patterns of
diversification to which all vertebrate families hold. These patterns, mapped
onto multidimensional space, constitute a phylogenetic space with distinct
properties. Firstly, phylogenetic space occupies only a portion of all possible
tree space, showing family-level phylogenies to be constrained to a limited range
of diversification patterns. Secondly, the geometry of phylogenetic space is
delimited by quantifiable trade-offs in tree size and the heterogeneity and stem
to-tip distribution of branching events. These trade-offs are indicative of the
instability of certain diversification patterns and effectively bound speciation
rates (for successful clades) within upper and lower limits. Finally, both the
constrained range and geometry of phylogenetic space are established by the
differential effects of macroevolutionary processes on patterns of
diversification. Given these properties, we show that the average path through
phylogenetic space over evolutionary time traverses several diversification
stages, each of which is defined by a different principal pattern of
diversification and directed by a different macroevolutionary process. The
identification of universal patterns and natural constraints to diversification
provides a foundation for understanding the deep-time evolution of biodiversity.
PMID- 27505867
TI - To the Editor: Prescribing opioids.
PMID- 27505868
TI - Trust the thyroid thermostat.
PMID- 27505869
TI - In Reply: Prescribing opioids.
PMID- 27505870
TI - To the Editor: Measles: More than the rash.
PMID- 27505871
TI - In Reply: Measles: More than the rash.
PMID- 27505872
TI - To the Editor: Acute liver failure.
PMID- 27505873
TI - In Reply: Acute liver failure.
PMID- 27505874
TI - Advanced-stage calciphylaxis: Think before you punch.
PMID- 27505875
TI - Geographic tongue.
PMID- 27505876
TI - Should patients with stable ischemic heart disease undergo revascularization?
PMID- 27505877
TI - Is a serum TSH measurement sufficient to monitor the treatment of primary
hypothyroidism?
PMID- 27505878
TI - Your patient has chronic leukemia: Now what?
AB - Although still in their infancy, biologic therapies for hematologic cancers are
making rapid strides, diminishing the role of chemotherapy and offering long-term
remission. More patients are surviving cancer and therefore are increasingly
being seen by primary care physicians, who must be aware of complications of
standard and newer treatments and how to manage them.
PMID- 27505879
TI - Renal failure in HCV cirrhosis.
PMID- 27505880
TI - Information management for clinicians.
AB - Clinicians are bombarded with information daily by social media, mainstream
television news, e-mail, and print and online reports. They usually do not have
much control over these information streams and thus are passive recipients,
which means they get more noise than signal. Accessing, absorbing, organizing,
storing, and retrieving useful medical information can improve patient care. The
authors outline how to create a personalized stream of relevant information that
can be scanned regularly and saved so that it is readily accessible.
PMID- 27505881
TI - Thrombotic thrombocytopenic purpura: The role of ADAMTS13.
AB - Thrombotic thrombocytopenic purpura (TTP) is an uncommon, life-threatening
disease requiring prompt diagnosis and initiation of therapeutic plasma exchange
to improve patient survival. However, diagnosis is often difficult because of
atypical presentations and signs and symptoms that resemble other conditions.
Measurements of ADAMTS13 activity, ADAMTS13 inhibitor, and ADAMTS13 autoantibody
are useful for diagnosing TTP, guiding therapy, and predicting relapse.
PMID- 27505882
TI - Is there a time limit for systemic menopausal hormone therapy?
AB - In deciding whether it is time to stop hormone therapy, in addition to the
patient's age we need to consider her preferences, symptoms, quality of life,
time since menopause, hysterectomy status, and personal risks of osteoporosis,
breast cancer, heart disease, stroke, and venous thromboembolism. This article
presents the evidence for and against extending hormone therapy and a guide for
making this highly individualized and shared decision.
PMID- 27505883
TI - Anemia of chronic kidney disease: Treat it, but not too aggressively.
AB - Anemia of renal disease is common and is associated with significant morbidity
and death. It is mainly caused by a decrease in erythropoietin production in the
kidneys and can be partially corrected with erythropoiesis-stimulating agents
(ESAs). However, randomized controlled trials have shown that using ESAs to
target normal hemoglobin levels can be harmful, and have called into question any
benefits of ESA treatment other than avoidance of transfusions.
PMID- 27505884
TI - Electrospun-Technology-Derived High-Performance Electrochemical Energy Storage
Devices.
AB - Electrospinning, as a novel nontextile filament technology, is an important
method to prepare continuous nanofibers and has shown its remarkable advantages,
such as a broadly applicable material system, controllable fiber size and
structure, and simple process. Electrospun nanofiber membranes prepared by
electrospinning have shown promising applications in many fields, such as
supercapacitors, lithium-ion batteries, and sodium-ion batteries, owing to their
large specific surface area and adjustable network pore structure. The principle
of electrospinning and key points relevant to its usage in the preparation of
high-performance electrochemical energy storage materials are reviewed herein
based on recent publications, particularly focusing on research progress of
relative materials. Also, this review describes a distinctive conclusion and
perspective on the future challenges and opportunities in electrospun
nanomaterials.
PMID- 27505885
TI - Kinesin-1 sorting in axons controls the differential retraction of arbor
terminals.
AB - The ability of neurons to generate multiple arbor terminals from a single axon is
crucial for establishing proper neuronal wiring. Although growth and retraction
of arbor terminals are differentially regulated within the axon, the mechanisms
by which neurons locally control their structure remain largely unknown. In the
present study, we found that the kinesin-1 (Kif5 proteins) head domain (K5H)
preferentially marks a subset of arbor terminals. Time-lapse imaging clarified
that these arbor terminals were more stable than others, because of a low
retraction rate. Local inhibition of kinesin-1 in the arbor terminal by
chromophore-assisted light inactivation (CALI) enhanced the retraction rate. The
microtubule turnover was locally regulated depending on the length from the
branching point to the terminal end, but did not directly correlate with the
presence of K5H. By contrast, F-actin signal values in arbor terminals correlated
spatiotemporally with K5H, and inhibition of actin turnover prevented retraction.
Results from the present study reveal a new system mediated by kinesin-1 sorting
in axons that differentially controls stability of arbor terminals.
PMID- 27505886
TI - Tensin 3 is a new partner of Dock5 that controls osteoclast podosome organization
and activity.
AB - Bone resorption by osteoclasts is mediated by a typical adhesion structure called
the sealing zone or actin ring, whose architecture is based on a belt of
podosomes. The molecular mechanisms driving podosome organization into
superstructures remain poorly understood to date, in particular at the osteoclast
podosome belt. We performed proteomic analyses in osteoclasts and found that the
adaptor protein tensin 3 is a partner of Dock5, a Rac exchange factor necessary
for podosome belt formation and bone resorption. Expression of tensin 3 and Dock5
concomitantly increase during osteoclast differentiation. These proteins
associate with the osteoclast podosome belt but not with individual podosomes, in
contrast to vinculin. Super-resolution microscopy revealed that, even if they
colocalize in the x-y plane of the podosome belt, Dock5 and tensin 3
differentially localize relative to vinculin in the z-axis. Tensin 3 increases
Dock5 exchange activity towards Rac, and suppression of tensin 3 in osteoclasts
destabilizes podosome organization, leading to delocalization of Dock5 and a
severe reduction in osteoclast activity. Our results suggest that Dock5 and
tensin 3 cooperate for osteoclast activity, to ensure the correct organization of
podosomes.
PMID- 27505887
TI - Shear-wave elasticity measurements of three-dimensional cell cultures for
mechanobiology.
AB - Studying mechanobiology in three-dimensional (3D) cell cultures better
recapitulates cell behaviors in response to various types of mechanical stimuli
in vivo Stiffening of the extracellular matrix resulting from cell remodeling
potentiates many pathological conditions, including advanced cancers. However, an
effective tool for measuring the spatiotemporal changes in elastic properties of
such 3D cell cultures without directly contacting the samples has not been
reported previously. We describe an ultrasonic shear-wave-based platform for
quantitatively evaluating the spatiotemporal dynamics of the elasticity of a
matrix remodeled by cells cultured in 3D environments. We used this approach to
measure the elasticity changes of 3D matrices grown with highly invasive lung
cancer cells and cardiac myoblasts, and to delineate the principal mechanism
underlying the stiffening of matrices remodeled by these cells. The described
approach can be a useful tool in fields investigating and manipulating the
mechanotransduction of cells in 3D contexts, and also has potential as a drug
screening platform.
PMID- 27505888
TI - Cellular functions of the ADF/cofilin family at a glance.
AB - The actin depolymerizing factor (ADF)/cofilin family comprises small actin
binding proteins with crucial roles in development, tissue homeostasis and
disease. They are best known for their roles in regulating actin dynamics by
promoting actin treadmilling and thereby driving membrane protrusion and cell
motility. However, recent discoveries have increased our understanding of the
functions of these proteins beyond their well-characterized roles. This Cell
Science at a Glance article and the accompanying poster serve as an introduction
to the diverse roles of the ADF/cofilin family in cells. The first part of the
article summarizes their actions in actin treadmilling and the main mechanisms
for their intracellular regulation; the second part aims to provide an outline of
the emerging cellular roles attributed to the ADF/cofilin family, besides their
actions in actin turnover. The latter part discusses an array of diverse
processes, which include regulation of intracellular contractility, maintenance
of nuclear integrity, transcriptional regulation, nuclear actin monomer transfer,
apoptosis and lipid metabolism. Some of these could, of course, be indirect
consequences of actin treadmilling functions, and this is discussed.
PMID- 27505889
TI - Proplatelet formation is selectively inhibited by collagen type I through Syk
independent GPVI signaling.
AB - Collagen receptors GPVI (also known as GP6) and integrin alpha2beta1 are highly
expressed on blood platelets and megakaryocytes, their immediate precursors.
After vessel injury, subendothelial collagen becomes exposed and induces platelet
activation to prevent blood loss. Collagen types I and IV are thought to have
opposite effects on platelet biogenesis, directing proplatelet formation (PPF)
towards the blood vessels to prevent premature release within the marrow cavity.
We used megakaryocytes lacking collagen receptors or treated megakaryocytes with
blocking antibodies, and could demonstrate that collagen-I-mediated inhibition of
PPF is specifically controlled by GPVI. Other collagen types competed for binding
and diminished the inhibitory signal, which was entirely dependent on receptor
proximal Src family kinases, whereas Syk and LAT were dispensable. Adhesion
assays indicate that megakaryocyte binding to collagens is mediated by
alpha2beta1, and that collagen IV at the vascular niche might displace collagen I
from megakaryocytes and thus contribute to prevention of premature platelet
release into the marrow cavity and thereby directionally promote PPF at the
vasculature.
PMID- 27505890
TI - 3D electron tomography of brain tissue unveils distinct Golgi structures that
sequester cytoplasmic contents in neurons.
AB - Macroautophagy is morphologically characterized by autophagosome formation.
Autophagosomes are double-membraned vesicles that sequester cytoplasmic
components for further degradation in the lysosome. Basal autophagy is paramount
for intracellular quality control in post-mitotic cells but, surprisingly, the
number of autophagosomes in post-mitotic neurons is very low, suggesting that
alternative degradative structures could exist in neurons. To explore this
possibility, we have examined neuronal subcellular architecture by performing
three-dimensional (3D) electron tomography analysis of mouse brain tissue that
had been preserved through high-pressure freezing. Here, we report that
sequestration of neuronal cytoplasmic contents occurs at the Golgi complex in
distinct and dynamic structures that coexist with autophagosomes in the brain.
These structures are composed of several concentric double-membraned layers that
appear to be formed simultaneously by the direct bending and sealing of discrete
Golgi stacks. These structures are labelled for proteolytic enzymes, and
lysosomes and late endosomes are found in contact with them, leading to the
possibility that the sequestered material could be degraded inside them. Our
findings highlight the key role that 3D electron tomography, together with tissue
rapid-freezing techniques, will have in gaining new knowledge about subcellular
architecture.
PMID- 27505891
TI - Seeing is believing - multi-scale spatio-temporal imaging towards in vivo cell
biology.
AB - Life is driven by a set of biological events that are naturally dynamic and
tightly orchestrated from the single molecule to entire organisms. Although
biochemistry and molecular biology have been essential in deciphering signaling
at a cellular and organismal level, biological imaging has been instrumental for
unraveling life processes across multiple scales. Imaging methods have
considerably improved over the past decades and now allow to grasp the inner
workings of proteins, organelles, cells, organs and whole organisms. Not only do
they allow us to visualize these events in their most-relevant context but also
to accurately quantify underlying biomechanical features and, so, provide
essential information for their understanding. In this Commentary, we review a
palette of imaging (and biophysical) methods that are available to the scientific
community for elucidating a wide array of biological events. We cover the most
recent developments in intravital imaging, light-sheet microscopy, super
resolution imaging, and correlative light and electron microscopy. In addition,
we illustrate how these technologies have led to important insights in cell
biology, from the molecular to the whole-organism resolution. Altogether, this
review offers a snapshot of the current and state-of-the-art imaging methods that
will contribute to the understanding of life and disease.
PMID- 27505892
TI - Visualizing red blood cell sickling and the effects of inhibition of sphingosine
kinase 1 using soft X-ray tomography.
AB - Sickle cell disease is a destructive genetic disorder characterized by the
formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell
(RBC) morphology changes that underlie the clinical manifestations of this
disease. Using cryogenic soft X-ray tomography (SXT), we characterized the
morphology of sickled RBCs in terms of volume and the number of protrusions per
cell. We were able to identify statistically a relationship between the number of
protrusions and the volume of the cell, which is known to correlate to the
severity of sickling. This structural polymorphism allows for the classification
of the stages of the sickling process. Recent studies have shown that elevated
sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production
contributes to sickling. Here, we further demonstrate that compound 5C, an
inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in
cellular morphology upon treatment suggests that this drug acts to delay the
sickling process. SXT is an effective tool that can be used to identify the
morphology of the sickling process and assess the effectiveness of potential
therapeutics.
PMID- 27505893
TI - The membrane trafficking and functionality of the K+-Cl- co-transporter KCC2 is
regulated by TGF-beta2.
AB - Functional activation of the neuronal K(+)-Cl(-) co-transporter KCC2 (also known
as SLC12A5) is a prerequisite for shifting GABAA responses from depolarizing to
hyperpolarizing during development. Here, we introduce transforming growth factor
beta2 (TGF-beta2) as a new regulator of KCC2 membrane trafficking and functional
activation. TGF-beta2 controls membrane trafficking, surface expression and
activity of KCC2 in developing and mature mouse primary hippocampal neurons, as
determined by immunoblotting, immunofluorescence, biotinylation of surface
proteins and KCC2-mediated Cl(-) extrusion. We also identify the signaling
pathway from TGF-beta2 to cAMP-response-element-binding protein (CREB) and Ras
associated binding protein 11b (Rab11b) as the underlying mechanism for TGF-beta2
mediated KCC2 trafficking and functional activation. TGF-beta2 increases
colocalization and interaction of KCC2 with Rab11b, as determined by 3D
stimulated emission depletion (STED) microscopy and co-immunoprecipitation,
respectively, induces CREB phosphorylation, and enhances Rab11b gene expression.
Loss of function of either CREB1 or Rab11b suppressed TGF-beta2-dependent KCC2
trafficking, surface expression and functionality. Thus, TGF-beta2 is a new
regulatory factor for KCC2 functional activation and membrane trafficking, and a
putative indispensable molecular determinant for the developmental shift of
GABAergic transmission.
PMID- 27505894
TI - The polarity protein Scribble positions DLC3 at adherens junctions to regulate
Rho signaling.
AB - The spatial regulation of cellular Rho signaling by GAP proteins is still poorly
understood. By performing mass spectrometry, we here identify the polarity
protein Scribble as a scaffold for the RhoGAP protein DLC3 (also known as StarD8)
at cell-cell adhesions. This mutually dependent interaction is mediated by the
PDZ domains of Scribble and a PDZ ligand (PDZL) motif in DLC3. Both Scribble
depletion and PDZL deletion abrogated DLC3 junctional localization. Using a RhoA
biosensor and a targeted GAP domain, we demonstrate that DLC3 activity locally
regulates RhoA-ROCK signaling at and Scribble localization to adherens junctions,
and is required for their functional integrity. In a 3D model of cyst
development, we furthermore show that DLC3 depletion impairs polarized
morphogenesis, phenocopying the effects observed upon Scribble knockdown. We thus
propose a new function for Scribble in Rho regulation that entails positioning of
DLC3 GAP activity at cell junctions in polarized epithelial cells.
PMID- 27505895
TI - Galpha12 is required for renal cystogenesis induced by Pkd1 inactivation.
AB - Mutation of PKD1, encoding the protein polycystin-1 (PC1), is the main cause of
autosomal dominant polycystic kidney disease (ADPKD). The signaling pathways
downstream of PC1 in ADPKD are still not fully understood. Here, we provide
genetic evidence for the necessity of Galpha12 (encoded by Gna12, hereafter
Galpha12) for renal cystogenesis induced by Pkd1 knockout. There was no phenotype
in mice with deletion of Galpha12 (Galpha12-/-). Polyinosine-polycytosine (pI:pC)
induced deletion of Pkd1 (Mx1Cre+Pkd1f/fGalpha12+/+) in 1-week-old mice resulted
in multiple kidney cysts by 9 weeks, but the mice with double knockout of Pkd1
and Galpha12 (Mx1Cre+Pkd1f/fGalpha12-/-) had no structural and functional
abnormalities in the kidneys. These mice could survive more than one year without
kidney abnormalities except multiple hepatic cysts in some mice, which indicates
that the effect of Galpha12 on cystogenesis is kidney specific. Furthermore, Pkd1
knockout promoted Galpha12 activation, which subsequently decreased cell-matrix
and cell-cell adhesion by affecting the function of focal adhesion and E
cadherin, respectively. Our results demonstrate that Galpha12 is required for the
development of kidney cysts induced by Pkd1 mutation in mouse ADPKD.
PMID- 27505897
TI - Local Ras activation, PTEN pattern, and global actin flow in the chemotactic
responses of oversized cells.
AB - Chemotactic responses of eukaryotic cells require a signal processing system that
translates an external gradient of attractant into directed motion. To challenge
the response system to its limits, we increased the size of Dictyostelium
discoideum cells by using electric-pulse-induced fusion. Large cells formed
multiple protrusions at different sites along the gradient of chemoattractant,
independently turned towards the gradient and competed with each other. Finally,
these cells succeeded to re-establish polarity by coordinating front and tail
activities. To analyse the responses, we combined two approaches, one aimed at
local responses by visualising the dynamics of Ras activation at the front
regions of reorientating cells, the other at global changes of polarity by
monitoring front-to-tail-directed actin flow. Asymmetric Ras activation in
turning protrusions underscores that gradients can be sensed locally and
translated into orientation. Different to cells of normal size, the polarity of
large cells is not linked to an increasing front-to-tail gradient of the PIP3
phosphatase PTEN. But even in large cells, the front communicates with the tail
through an actin flow that might act as carrier of a protrusion inhibitor.
PMID- 27505896
TI - Deep nuclear invaginations are linked to cytoskeletal filaments - integrated
bioimaging of epithelial cells in 3D culture.
AB - The importance of context in regulation of gene expression is now an accepted
principle; yet the mechanism by which the microenvironment communicates with the
nucleus and chromatin in healthy tissues is poorly understood. A functional role
for nuclear and cytoskeletal architecture is suggested by the phenotypic
differences observed between epithelial and mesenchymal cells. Capitalizing on
recent advances in cryogenic techniques, volume electron microscopy and super
resolution light microscopy, we studied human mammary epithelial cells in three
dimensional (3D) cultures forming growth-arrested acini. Intriguingly, we found
deep nuclear invaginations and tunnels traversing the nucleus, encasing
cytoskeletal actin and/or intermediate filaments, which connect to the outer
nuclear envelope. The cytoskeleton is also connected both to other cells through
desmosome adhesion complexes and to the extracellular matrix through
hemidesmosomes. This finding supports a physical and/or mechanical link from the
desmosomes and hemidesmosomes to the nucleus, which had previously been
hypothesized but now is visualized for the first time. These unique structures,
including the nuclear invaginations and the cytoskeletal connectivity to the cell
nucleus, are consistent with a dynamic reciprocity between the nucleus and the
outside of epithelial cells and tissues.
PMID- 27505899
TI - Editorial: Evidence-Informed Reviews-Moving Occupational Therapy Practice and
Science Forward.
PMID- 27505900
TI - Does a Falls Prevention Program Impact Perceived Participation in Everyday
Occupations? A Pilot Randomized Controlled Trial.
AB - This study aimed to evaluate the effectiveness of a multi-disciplinary, client
centered, fall prevention program on the experiences of participation and
autonomy in everyday occupations among community-dwelling older adults. In total,
131 older adults (65+) were included and randomly allocated into two groups.
Intention-to-treat analysis was used. Results of this pilot study showed that the
program had a limited effect on the subjective experiences of participation and
autonomy in everyday occupations among the participants. However, a trend of
increased perceived participation and a decrease in the experience of perceived
problems with participation among the participants in the intervention group was
shown. Perceived participation and autonomy seem to be subjective experiences,
and they seem to vary depending on the individual. To properly understand the
impact of fall prevention interventions on participation and autonomy,
measurements that capture both subjective and objective experiences are essential
to use.
PMID- 27505898
TI - Persistent nuclear actin filaments inhibit transcription by RNA polymerase II.
AB - Actin is abundant in the nucleus and it is clear that nuclear actin has important
functions. However, mystery surrounds the absence of classical actin filaments in
the nucleus. To address this question, we investigated how polymerizing nuclear
actin into persistent nuclear actin filaments affected transcription by RNA
polymerase II. Nuclear filaments impaired nuclear actin dynamics by polymerizing
and sequestering nuclear actin. Polymerizing actin into stable nuclear filaments
disrupted the interaction of actin with RNA polymerase II and correlated with
impaired RNA polymerase II localization, dynamics, gene recruitment, and reduced
global transcription and cell proliferation. Polymerizing and crosslinking
nuclear actin in vitro similarly disrupted the actin-RNA-polymerase-II
interaction and inhibited transcription. These data rationalize the general
absence of stable actin filaments in mammalian somatic nuclei. They also suggest
a dynamic pool of nuclear actin is required for the proper localization and
activity of RNA polymerase II.
PMID- 27505901
TI - Clinical Assessments as Predictors of Primary On-Road Outcomes in Parkinson's
Disease.
AB - Parkinson's disease (PD) is a neurodegenerative disorder that affects fitness to
drive. Research that has examined clinical predictors of fitness to drive in PD,
using the on-road assessment as the gold standard, has generally used a
dichotomous pass/fail decision. However, on-road assessments may also result in
one of two additional outcomes (pass with recommendations, or fail-remediable).
Individuals within these subgroups may benefit from interventions to improve
their fitness to drive abilities. This study investigated clinical predictors
that could be indicative of the pass, pass with recommendations, or fail
remediable categories for drivers with PD (N = 99). Trails B, Left Finger to Nose
Test, and contrast sensitivity measures were identified as significant predictors
for the pass, and pass with recommendations subgroups. No significant predictors
were identified for the fail-remediable subgroup. Results from this study provide
a foundation for clinicians to identify drivers who can benefit from
recommendations to preserve their driving abilities.
PMID- 27505902
TI - Development of the Adolescent and Young Adult Activity Card Sort.
AB - Emerging adulthood defines transition to employment, higher education, and
domestic life. This study describes the development of an assessment of self
reported participation in a range of age-appropriate activities. Item selection
was established from literature review, feedback from youth and professionals,
the former Adolescent Activity Card Sort (AACS), and the original Activity Card
Sort (ACS). Iterative item selection occurred with three separate samples of
emerging adults and six professionals. Test-retest reliability was evaluated. The
Adolescent and Young Adult Activity Card Sort (AYA-ACS) consists of chores (11
items), leisure (13), social (10), health and fitness (9), work (10), education
(8), and parenting (9). Test-retest reliability showed significant moderate to
substantial Kappa agreement (.48-.85) for all domains except parenting (kappa =
.15). This preliminary study describes the development of the AYA-ACS to be used
with individuals who encounter challenges when transitioning to young adulthood.
PMID- 27505903
TI - Meaningful Components of Exercise and Active Recreation for Spinal Cord Injuries.
AB - This qualitative study used focus groups to identify meaningful components of
exercise and active recreation (E/AR) related to consistent participation for
those with spinal cord injury (SCI). Transcripts from each focus group were
analyzed with classical content analysis, grounded theory coding, and meaning
condensation using the International Classification of Function, Disability and
Health (ICF). Variables within each of the ICF domains (body structures and
functions, activities/participation, and environment) were indicated as
meaningful components leading to increased participation, independence, and
reasons why people consistently participated in E/AR. Occupational therapists can
utilize these components to implement therapeutic intervisions, which provide
clients with a sense of purpose and being, thus improving outcomes in meaningful
occupations.
PMID- 27505904
TI - Occupational Therapists' Views of Nussbaum's Life Capability: An Exploratory
Study.
AB - Life Capability is the first and most fundamental of Nussbaum's 10 Central Human
Functional Capabilities (CHFCs). This capability refers to a person having a
quality life of normal duration. The purpose of this study was to explore the
views' of occupational therapists about Life Capability, specifically, their
perspectives of this capability and its perceived relevance to practice. Semi
structured interviews with 14 occupational therapists in British Columbia,
Canada, were conducted and thematically analyzed. Within this Canadian context,
three themes emerged regarding occupational therapists' views about Life
Capability: basic human right, quality of life, and longevity. Occupational
therapists appear to view Life Capability as being consistent with the values of
the occupational therapy profession. Nussbaum's other CHFCs warrant study to
explore the degree to which the Capabilities Approach could complement existing
occupational therapy theories, science, and practice.
PMID- 27505905
TI - Comment on "Efficacy of an Occupational Therapy Driving Intervention for
Returning Combat Veterans".
PMID- 27505907
TI - ANTI-INFLAMMATORY, ANALGESIC AND ANTIPYRETIC ACTIVITIES OF THE AQUEOUS METHANOLIC
EXTRACT OF BERBERIS CALLIOBOTRYS IN ALBINO MICE.
AB - The aqueous methanolic extract of stem part of Berberis calliobotiys (AMEBC) was
evaluated for anti-inflammatory, analgesic and antipyretic activities in albino
mice. Anti-inflammatory activity was evaluated by using carrageenan and albumin
induced paw edema, while the analgesic effect was assessed by using formalin
induced paw licking and acetic acid induced abdominal writhing in mice. The
brewer's yeast-induced pyrexia model was used for antipyretic investigation.
Ibuprofen (40 mg/kg) was used as a standard drug in all the three models. The
aqueous methanolic extract at both (250 mg/kg and 500 mg/kg) doses, showed highly
significant (p < 0.001) reduction in paw edema induced by carrageenan and
albumin. Moreover, the aqueous methanolic extract also highly significantly (p <
0.001) reduced (87%) the formalin-induced paw licking at 500 mg/kg. The highly
significant (p < 0.001) reductions (24.48% and 37.9%) was also observed in the
number of writhings. Furthermore, aqueous methanolic extract also demonstrated
significant (p < 0.001) antipyretic activity against yeast induced pyrexia. The
maximum effect was observed in all the three parameters at 500 mg/kg dose. The
results suggest a potential benefit of the aqueous methanolic extract of Berbeis
calliobotrys in treating conditions associated with inflammation, pain and fever.
PMID- 27505908
TI - Parenting in practice.
PMID- 27505909
TI - Sentinel node biopsy should not be the standard of care for patients with
intermediate and thick melanomas.
PMID- 27505910
TI - MSLT-I: Comparing apples to antelopes.
PMID- 27505911
TI - MSLT-I: Comparing apples to antelopes--Reply.
PMID- 27505912
TI - Sentinel node biopsy for melanoma: The medical oncology perspective.
PMID- 27505913
TI - Sentinel node biopsy in patients with intermediate and thick melanomas - A
balanced view.
PMID- 27505914
TI - Training for general practice: How Australia's programs compare to other
countries.
AB - BACKGROUND: General practice in Australia and internationally has undergone a
dramatic transformation over the past half century in terms of recognition,
academic status, organisation and funding. Training pathways have also evolved in
response to this changing environment. OBJECTIVES: This paper compares some of
the features of Australian and international general practice training using the
educational standards developed by the World Organization of Family Doctors'
(WONCA) Working Party on Education as a framework. DISCUSSION: General practice
training in Australia, particularly rural training, is strong by international
standards, but more lessons can still be learnt from other settings. Local
contextual factors mean there are substantial differences in training across
jurisdictions, but there are a number of similarities. There is increasing
attention being paid to the many roles of a general practitioner, and the
importance of a formalised, structured and well-resourced training program. More
needs to be done internationally to ensure high-level primary care is available
to all people, particularly the underserved.
PMID- 27505915
TI - Global family medicine and Australian general practice.
PMID- 27505916
TI - Adult-onset asthma.
PMID- 27505917
TI - Not to attend a pharmaceutical company function is a moral not an ethical
decision.
PMID- 27505918
TI - Not to attend a pharmaceutical company function is a moral not an ethical
decision--Reply.
PMID- 27505919
TI - Considering domestic violence in clinical practice.
PMID- 27505921
TI - Reply.
PMID- 27505920
TI - Sleep problems in children.
PMID- 27505922
TI - Higher education in New South Wales for permanent wheelchair users.
PMID- 27505923
TI - What general practitioners need to know about veterans' health.
PMID- 27505924
TI - Food insecurity.
PMID- 27505925
TI - Reply.
PMID- 27505926
TI - THORACOSTOMY PHILOSOPHY.
PMID- 27505927
TI - OUT-OF-SIGHT AIRWAY.
PMID- 27505928
TI - NOT SO 'COMMON'.
PMID- 27505929
TI - DEXTROSE DOSING.
PMID- 27505930
TI - ALTITUDE ILLNESS.
PMID- 27505931
TI - INTO THE WILD.
PMID- 27505932
TI - No other option.
PMID- 27505934
TI - LEADING THE WAY TO SAVES.
PMID- 27505935
TI - LEARNING TO DANCE WITH AN ELEPHANT.
PMID- 27505933
TI - Lifesaving Field Amputations.
PMID- 27505936
TI - BEYOND BLOOD SUGAR.
AB - Because POC testing has been shown to alter prehospital care in up to 30% of its
uses, it may be logical for prehospital systems to consider implementing a POC
testing system. Information gleaned from the i-STAT data can be used to treat
electrolyte imbalances, adjust medications and ventilator settings, and even
change IV fluid use. MIH providers can also use the data from POC testing to
provide important feedback to physicians about enrolled patients. All of these
uses support critical clinical decision making by field EMS providers, and will
perhaps even help promote the value proposition we're all striving for in our EMS
delivery models.
PMID- 27505937
TI - BREAKING GLASS.
PMID- 27505938
TI - DRIVER'S ED.
PMID- 27505939
TI - THE POWER OF ZAMBIKES.
PMID- 27505940
TI - We never stop learning.
PMID- 27505941
TI - Celebrating nurses' contributions.
PMID- 27505942
TI - Leaders recognized and celebrated.
PMID- 27505943
TI - Validity of psychometric instruments.
PMID- 27505944
TI - Transitions: Adjusting to Working Life.
PMID- 27505945
TI - If I Knew Then What I Know Now....
PMID- 27505946
TI - Cardiology and oncology care providers join forces.
PMID- 27505947
TI - Medical assistance in dying: What can nurses expect after June 6?
PMID- 27505949
TI - The globalization of Paisly Symenuk.
PMID- 27505948
TI - Walking side by side on a journey of reconciliation.
PMID- 27505950
TI - Making her career her own.
PMID- 27505951
TI - Blood and plasma collection shouldn't be privatized.
PMID- 27505952
TI - [Comparative study on the clinic effects of arthroscopic reconstructions of
single-bundle and double-bundle anterior cruciate ligament].
PMID- 27505953
TI - [Case-control study on Chinese medicine fumigation and massage therapy for the
treatment of knee stability and func tional recovery after anterior cruciate
ligament reconstruction operation].
AB - OBJECTIVE: To study clinical outcomes of Chinese medidine fumigation and massage
therapy for the treatment of knee stability and functional recovery after
anterior cruciate ligament reconstruction operation,and to explore the effect on
tendon-bone healing. METHODS: Total 50 patients were divided into two groups: the
control group (normal rehabilitation therapy group),the treatment group (Chinese
medicine fumigation and manipulation group). There were 25 patients in the
control group, including 16 males and 9 females, who were treated with isometric
muscle training, with the gradually enlarging amplitude of flexion and
progressive loading of bearing training for knee recovery. There were 25 patients
in the treatment group, including 15 males and 10 females,who were treated with
the conventional rehabilitation therapy combined with Chinese medicine fumigation
and massage therapy. The Chinese herbs named as Haitongpi decoction was steamed
by a special equipment to fumigate the knee after operation; Based on the
biomechanical parameters of the ligament reconstruction, the massage therapy was
designed to control the degree of the knee flexion and release the adhesion for
early recovery of knee functions. The Lysholm knee function evaluation system was
used, and MRI examination was performed to measure the change in width of
ligament tunnel in femur and tibia to evaluate the safety and stability of the
treatment. RESULTS: Lysholm system showed that two groups both had improving
results from the 1st month after operation to the 3rd month (treatment group,
F=36.54, P<0.05; the control group, F=28.12, P<0.05), and the results of the
treatment group was better than that of the control group at the observation
point (the 1st month, t=0.105, P<0.05; the 3rd month, t=5.361, P<0.01). There was
no difference between the two groups when evaluating the bone and tendon healing
3 and 12 months after operation (P>0.05), indicating that Chinese rehabilitation
therapy was a safety treatment without the influence on the loosing of tendon.
CONCLUSION: Chinese medicine fumigation and massage therapy can early improve the
knee function after the anterior cruciate ligament reconstruction operation
without the disturbance of the knee stability.
PMID- 27505954
TI - [Clinical effect of staged repair and reconstruction of multiple ligament
injuries in knee joints].
AB - OBJECTIVE: To evaluate clinical outcomes of anterior cruciate ligament (ACL) and
posterior cruciate ligament (PCL) reconstruction under arthroscopy combined with
limited open repair of medial collateral ligament (MCL) for the treatment of
multiple ligament injuries of knee joints. METHODS: From March 2006 and June
2012,the data of 14 patients (14 knees) with multiple injuries of ACL, PCL, and
MCL were collected. There were 8 males and 6 females with an average age of (31.8
+/- 8.1) years old (ranged, 20 to 49 years old). All the patients were performed
with X-ray and MRI examination, and the results showed that 10 patients had
combined with injuries of anterior cruciate ligament (ACL), posterior cruciate
ligament (PCL) and medial collateral ligament (MCL); 4 patients had ALC,PCL and
posterolateral corner (PLC) injuries. Four patients had medial meniscus injuries
and 2 patients had lateral meniscus injuries. The MCL,PLC and meniscus injuries
were treated with operation on the first stage, and functional exercises were
performed 3 weeks after fixation. The reconstruction operation of ACL and (or)
PCL was performed at the second stage under arthroscopy 3 to 6 months later when
the movement range of knee joint recovered to the normal level with obvious
relaxation. RESULTS: All incisions healed by primary intention. All the patients
were followed up with a mean duration of 48.9 months (ranged, 24 to 80 months).
The Lysholm score was improved from preoperative 19.6 +/- 0.9 to the latest
follow-up 87.1 +/- 2.8 (t=12.3, P<0.01). The International Knee Documentation
Committee (IKDC) rating: 9 cases nearly recovered to normal, 5 cases were
abnormal. CONCLUSION: For multiple ligament injuries in the knee, staged repair
and reconstruction can effectively restore knee joint stability and function.
PMID- 27505955
TI - [Case-control study on two suturing methods for the repairing of complete rupture
of the deltoid ligament].
AB - OBJECTIVE: To compare clinical outcomes between two suturing methods using non
absorbable materials through drilling the bone and suturing anchors for the
treatment of complete rupture of the deltoid ligament. METHODS: From January 2009
to January 2013, 58 hospitalized patients with ankle fracture combined with
complete rupture of the deltoid ligament were treated with suturing using non
absorbable materials through drilling the bone or suturing anchors. There were 29
patients who received suturing treatments using non absorbable materials through
drilling the bone (Group A), including 18 males and 11 females, with an average
age of (39.76 +/- 11.81) years old. According to the Lauge-Hansen classification,
12 patients had supination external rotation (SER) injuries with IV degree, 5
patients had pronation external rotation (PER) injuries with III degree, 10
patients had PER injuries with IV degrss, and 2 patients had pronation abduction
injuries with III degree. There were 29 patients who received treatments with
suturing using anchors (Group B), including 14 males and 15 females, with an
average age of (41.79 +/- 13.28) years old. According to the Lauge-Hansen
classification,9 patients had SER injuries with IV degree, 6 patients had PER
injuries with III degree,13 patients had PER injuries with IV degree, and 1
patient had pronation abduction injuries with III degree. All the patients were
treated with open reduction and internal fixation, as well as reconstruction of
deltoid ligaments to restore the stability of the medial ankle structures. The
clinical examination, imaging evaluation, American society for ankle surgery
(AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to
evaluate the clinical results after operation, and the results of the two groups
were compared and analyzed statistically. RESULTS: The follow-up duration of the
58 patients ranged from 23 to 40 months,with an average of 27.3 months. All the
patients had fracture union, and the mean healing time was 12.3 weeks (ranged, 10
to 17 weeks). There were no incision complications and ankle instability. There
were no significant differences between two groups in AOFAS (P=0.666) and the VAS
(P=0.905). CONCLUSION: Treatments of complete rupture of the deltiod ligaments
with the two suturing methods get similar good clinical effects, but the suturing
using non absorbable materials through drilling the bone has several advantages
such as reducing the financial burden of patients, saving social medical
resources and avoiding the shortcoming in difficult removal of anchor suture.
PMID- 27505956
TI - [Relationship between screw numbers and severity of tibial bone defect in primary
total knee arthroplasty].
AB - OBJECTIVE: To summarize experience of using screws and cement to rebuild tibial
bone defect in primary total knee arthroplasty (TKA) and to discuss the
relationship between the number of required screws and the severity of tibial
bone defects. METHODS: From July 2009 to May 2015, 34 patients (40 knees) with
varus knees underwent TKA, and the screw and cement technique was used to rebuild
medial tibia plateau during operation. There were 8 males (8 knees) and 26
females (32 knees), and the average age was (65.00 +/- 7.25) years old (ranged,55
to 82 years old). One to 6 screws were used in each case. Extension stems were
used in 2 cases (4 and 5 screws was used respectively). The area percentages of
the bone defects measured as defect area/tibia plateau area, depth of each
defect, the number of screws needed in each case, were all used to determine the
relationship between the number of screws and the area percentage in certain
depth of bone defect by statistic methods, as well as the relationship between
screw number and defect depth. RESULTS: All the patients were followed up and the
average duration was 24 months (ranged, 1 to 72 months). The average preoperative
HSS score was 43.33 +/- 6.11 (ranged, 32 to 51 scores). Whereas the average
postoperative HSS score was 92.15 +/- 4.64 (ranged,83 to 96 scores). The
preoperative individual scores including pain, function, activity, nuscle
strength, flexion deformity and stability were all improved compared with
preoperation,and the differences were statistically significant. All the patients
received normal alignment postoperatively, femoraltibial angle was improved from
(167.00 +/- 6.39) degrees preoperatively to (175.00 +/- 2.69) degrees
postoperatively, the tibial angle was improved from (78.09 +/- 4.51) degrees
preoperatively to (88.75 +/- 1.24) degrees postoperatively. Both area percentage
and depth of bone defect in a fitting Ologistic model had a significant
statistical relationship with the screw number, and a rectangular coordinate
system could be formed according to the relationship. CONCLUSION: Screws and
cement technique is a simple, safe and convenient method to rebuild tibial bone
defects in primary TKA and its short-term and midterm effect are both reliable.
During opera- tion, according to the rectangular coordinate system, the screw
number needed in the operation can be inferred form th area and depth of tibia
defect, which could have a guiding function in surgery.
PMID- 27505957
TI - [Clinical efficacy of cannulated screw fixation with percutaneous Poking
reduction for the treatment of calcaneal fracture].
AB - OBJECTIVE: To investigate the clinical efficacy of cannulated screw fixation with
percutaneous Poking reduction for the treatment of Sanders II, III calcaneal
fracture. METHODS: From January 2012 to January 2014, 19 patients with Sanders
II, III calcaneal fracture were treated with cannulated screw fixation with
percutaneous Poking reduction. There were 14 males and 5 females, ranging in age
from 19 to 58 years old, with an average age of (38.3 +/- 4.1) years old. The
changes of Bohler angle and Gissane angle were measured and compared
preoperatively and postoperatively to observe the recovery of the articular
surface. The Maryland Foot Score was used to evaluate operation outcomes.
RESULTS: All the patients were followed up, and the duration ranged from 12 to 28
months with a mean of (22.3 +/- 5.3) months. The Bohler angle and Gissane angle
were improved significantly after operation compared with those before operation
(P < 0.05). The Maryland score was 83.2 +/- 8.4. CONCLUSION: Treatment of
calcaneal fractures with screw fixation with percutaneous Poking reduction has
several advantages such as satisfactory outcome,less damage, fewer complications,
quicker recovery, and shorter hospital stay,and it is one of the effective
treatments for Sanders II and III calcaneal fractures.
PMID- 27505958
TI - [Unilateral fixation combined with interbody fusion for the treatment of lumbar
degenerative instability via a paraspinal intermuscular approach under MAST
Quadrant retractor].
AB - OBJECTIVE: To study clinical effects of unilateral pedicle screw-rod system
fixation combined with the single the cage of interbody fusion in the treatment
of lumbar degenerative instability via paraspinal intermuscular approach under
MAST Quadrant retractor. METHODS: From February 2010 to December 2011, 39
patients with lumbar degenerative instability after invalid conservative
treatment were treated with unilateral fixation combined with interbody fusion
via the paraspinal intermuscular approach under MAST Quadrant retractor. The
indexes such as the operative time, blood loss, complications, VAS pain scores,
JOA (subjective symptoms of low back pain,lower limb pain and numbness, sensory
disturbance, movement disorders) scores, modified Macnab criteria for curative
effect evaluation were observed before treatment, at the 1st month after
treatment and the latest follow-up. The intervertebral fusion was studied on the
X-ray at the latest follow-up. RESULTS: All the patients were followed up, and
the mean during was (22.3 +/- 8.6) months. The operation time was (138 +/- 46)
min, and the amount of bleeding was (335 +/- 152) ml. There were no complications
such as cerebrospinal fluid leakage and spinal nerve injury during operation, and
no incision infection after operation. The VAS pain score was reduced from
preoperative 7.93 +/- 1.27 to 2.05 +/- 1.18 on the 1st month after operation and
1.89 +/- 0.42 at the latest follow-up. The JOA total score was improved from
preoperative 1.59 +/- 0.42 to 8.86 +/- 0.37 on the 1st month and 9.02 +/- 0.29 at
the latest follow-up. According to modified Macnab criteria, there were 17 cases
got an excellent result, 19 good, 3 case fair. Thirty-five patients got
intervertebral bony fusion at the latest follow-up. CONCLUSION: Unilateral
pedicle screw-rod system fixation combined with single cage interbody fusion in
the treatment of lumbar degenerative instability via paraspinal intermuscular
approach under MAST Quadrant retractor is a safe, minimally invasive,
satisfactorily effective methods to treat lumbar degenerative instability.
PMID- 27505959
TI - [Analysis and comparison about musculoskeletal ultrasonoLranhv and x-rav of knee
osteoarthritis].
AB - OBJECTIVE: To analyze and compare the characteristics of musculoskeletal
ultrasonography and X-ray of knee osteoarthritis, and to investigate the
advantages of them. METHODS: According to the inclusion and exclusion criteria,
57 cases (66 knees) were collected from February 2015 to May 2015. Among them,
there were 48 females and 9 males with an average age of (58.9 +/- 9.8) years old
(ranged, 41 to 78 years old). The main symptoms included unilateral or bilateral
knee pain and locked joints explicit areas of tender points. The mean course of
disease was (13.6 +/- 3.0) months. The results of musculoskeletal ultrasound and
X-ray examinations were analyzed. RESULTS: According to Kellgren-Lawrence
classification of knee joint on the X-ray: the musculoskeletal ultrasound results
of patients with I degree synovial hyperplasia in 9 cases, joint effusion in 20
cases, meniscal disease in 13 cases, patellar pad inflammation in 5 cases, and
patellar lesion in 8 cases. The musculoskeletal ultrasound results of patients
with III degree: synovial hyperplasia in 20 cases,joint effusion in 31 cases,
meniscal disease in 22 cases, patellar pad inflammation in 16 cases and patellar
lesion in 17 cases. The musculoskeletal ultrasound results of patients with III
degree: synovial hyperplasia in 6 cases,joint effusion in 6 cases, meniscal
disease in 7 cases, patellar pad inflammation in 7 cases and patellar lesion in 5
cases. CONCLUSION: The musculoskeletal ultrasound can detect the pathological
changes of knee soft tissue sensitively, provide an accurate location of
lesions,and find lesions early. The musculoskeletal ultrasound should be
applicated in the diagnosis of knee osteoarthritis.
PMID- 27505960
TI - [Clinical research on the efficiency of physical examinations used for diagnosis
of subacromial impingement syndrome].
AB - OBJECTIVE: To evaluate the reliability and diagnosis accuracy of 5 special tests
used for the diagnosis of subacromial impingement syndrome (SAIS). METHODS: A
prospective blinded cohort study was taken,in which 105 patients with shoulder
pain were reviewed. All the patients took 5 special syndrome tests including Neer
syndrome, Hawkins-Kennedy syndrome, painful arc empty can test and external
rotation resistance test, also underwent arthroscopic surgical examination. The
Nikolaus's criterion was regarded as a golden standard for SAIS. Data accuracy
analysis was calculated through a receiver operating characteristic (ROC) curve,
sensitivity, specificity, positive likelihood ratio (+LR) and negative likelihood
ratio (-LR). The binary Logistic regression analysis was used to find out the
best test combination for ruling in or out SAIS. The interrater reliability was
assessed by the Kappa coefficient and percent agreement. RESULTS: The ROC
analysis indicated a significant area under the curve (AUC) (AUC=0.62 to 0.73,
P<0.05) for all tests except the Hawkins-Kennedy. Tests with a +LR greater or
equal to 2.0 were the painful arc,empty can,external rotation resistance, Tests
with a-LR less than 0.5 were Neer,painful are ,external rotation resistance. The
regression analysis found the painful arc, empty can and external rotation
resistance made the best combination for diagnosis SAIS,while the painful are and
external rotation resistance made the best combination for ruling out SAIS. The
difference of ROC analysis was significant with a cut-off of 3 positive tests out
of 5 tests. All tests had moderate to good agreement (Kappa=0.42 to 0.71).
CONCLUSION: The single test of painful arc, empty can and external rotation
resistance, as well as 3 or more positive tests of the 5 tests can help confirm
the diagnosis of SAIS, while the single test of Neer, painful arc and external
rotation resistance are help rule out the diagnisis of SAIS. The tests of painful
arc, empty can and ex ternal rotation resistance are the best combination for the
diagnosis of SAIS (when 2 or more are positive), while the tests of painful arc
and external rotation resistance are the best combination for ruling out SAIS
(when both are negative)
PMID- 27505961
TI - [Biomechanical analysis on the correlation between iliac rotation displacement
and L(4,5) disc degeneration].
AB - OBJECTIVE: To study the biomechanical relationship between iliac rotation
displacement and L(4,5) disc degeneration, and to provide clinical evidences for
the prevention and treatment of L(4,5) disc degeneration and herniation. METHODS:
From March 2012 to February 2014,68 patients with lumbar disc herniation combined
with sacroiliac joint disorders were selected. Among them, 42 patients with
L(4,5) disc herniation combined with sacroiliac joint disorders included 22 males
and 20 females, ranging in age from 19 to 63 years old, with an average of (51.78
+/- 20.18) years old, and the duration of the disease ranged from 1 to 126 months
with an average of (11.18 +/- 9.23) months. Twenty-six patients with L5S1 disc
herniation combined with sacroiliac joint disorders included 11 males and 15
females, ranging in age from18 to 65 years old with an average of (45.53 +/-
27.23) years old, and the duration of the disease ranged from 0.5 to 103 months
with an average of (11.99 +/- 12.56) months. Sixty-eight anteroposterior lumbar
radiographs, 68 lateral lumbar radiographs,and 68 pelvic plain films were taken.
The degree of lumbar scoliosis, pelvic tilt,and disc thickness were measured. The
correlation between pelvic tilt and lumbar scoliosis ,lumbar scoliosis and disc
thickness were studied by using linear and regression methods. The hiomechanical
analysis was performed. RESULTS: There was a positive correlation between pelvic
tilt and lumbar scoliosis in patients with L(4,5) disk herniation (R=0.49,
P=0.00). There was a causal relationship and good linear proportional
relationship (Y=3.05+1.07X, P=0.00) in the two variables. There was a negative
correlation between lumbar scoliosis and intervertebral space in male patients
with L (4,5) disk herniation (R = -0.50, P=0.01). There was a causal relationship
and good linear proportional relationship in the two variables (Y=13.09-0.27X,
P=0.02). But there was a positive correlation between lumbar scoliosis and
intervertebral space in male patients with L5S1 disk herniation (R=0.46, P=0.04).
CONCLUSION: Iliac rotational displacement are closely related with L(4,5) disc
degeneration and herniation in biomechanics. A new concepts and therapeutic
approach is provided for clinical treatment of chronic and refractory herniation
of L(4,5) disc in patients
PMID- 27505962
TI - [Case-control study on three spinal rotation manipulations for the treatment of
lumbar disc herniation].
AB - OBJECTIVE: To evaluate the efficacy and safety of three different spinal rotation
manipulations for the treatment of lumbar disc herniation. METHODS: From
September 2011 to April 2013,180 patients diagnosed as lumbar disc herniation
were randomly divided into seat fixed rotation group (A), lateral position
rotation group (B) and supine position rotation group (C) by using a digital
table. Finally 10 patients were excluded and dropped, 170 patients were included
in the study. There were 57 patients in group A, 57 patients in group B and 56
patients in group C. Baseline demographic characteristics of patients, clinical
findings and indexes of health status had no statistically differences among
three groups (P > 0.05). The manipulation was performed every other day, and the
treatment duration for all patients was 3 weeks. Body pain (BP), Physical
function (PF) in SF-36, Oswestry Disability Index (ODI) and adverse reactions
were observed statistically 6 weeks, 3 months, 6 months, one year and two years
after finishing treatment. RESULTS: BP, PF scores in 3 groups were significantly
improved and ODI scores were significantly lower than those before treatment and
the differences were statistically significant (P < 0.05); However, there was no
significant difference among three groups in the BP, PF and ODI scores (P >
0.05). There were no obvious and serious adverse reactions among these groups.
CONCLUSION: Based on the theory of dislocation of bone joints in TCM, three kinds
of spinal rotation manipulations can be used safely for the treatment of lumbar
disc herniation, and the efficacy was similar.
PMID- 27505963
TI - [Effect of acupuncture therapy on patients with low back pain: a Meta-analysis].
AB - OBJECTIVE: To systematically review the clinical efficacy of acupuncture on the
patients with low back pain (LBP). METHODS: Randomized controlled trials (RCTs)
about pure acupuncture therapy versus other treatments in treating LBP were
electronically searched in PubMed, CBM, EMbase, The Cochrane Library, CNKI, VIP
and Wanfang Data from January 2004 to May 2014. The observed index on the results
were the changed scores of VAS, ODI, JOA and RMDQ. Two reviewers independently
screened the literatures according to the inclusion and exclusion criteria, as
well as the extracted data, and assessed the methodological quality. The results
of Meta-analysis was conducted by RevMan 5.2 software. RESULTS: Ten RCTs involved
751 patients were finally included. The results of Meta-analysis indicated that
the role of pure acupuncture group in improving the VAS score was better than
that of the control group, and the combined effect size was RR = -.32, 95% CI (
1.41, -1.22); Z=27.28, P<0.00001; the role of pure acupuncture group in improving
the ODI score was better than that of the control group, and the combined effect
size was RR = -5.07, 95% CI (-7.50, -2.65); Z=4.10, P<0.0001; the role of pure
acupuncture group on improved JOA score was better than that of the control group
and the combined effect size was RR=2.83, 95% CI (2.02, 3.63), Z=6.90, P<0.00001.
The role of pure acupuncture group in improving the RMDQ score was better than
that of the control group, and the combined effect size was RR = -2.80, 95% CI (
3.49, -2.11), Z=7.95, P<0.00001. CONCLUSION: The result of meta-analysis
demonstrates that pure acupuncture may have a favorable effect on self-reported
pain and functional limitations in LBP patients.
PMID- 27505964
TI - [Surgical treatment of multiple ligament injuries of knee joints].
AB - OBJECTIVE: To study operative effects for the treatment of multiple ligament
injuries of knee joints. METHODS: From 2008 to 2013, 26 patients (17 males and 9
females) with multiple ligament injuries of knee joints were treated surgically.
The average age was 40.7 years old, ranging from 29 to 55 years old. All the
patients were treated with arthroscopic reconstruction of cruiate ligament with
autogenous or allogeneic hamstrings and tendon, and at the same time received
repair of medial collateral ligament and lateral collateral ligament, as well as
the treatment of exterior and interior complex injuries. Nine patients received
second stage operation after the initial operation for mistake or missed
diagnosis, and other patients were treated at the first stage. The Lysholm
scoring system was used to evaluate function and stability of knee joints before
and after operation. RESULTS: All the patients were followed up for an average
duration of 1.6 years (ranged, 0.8 to 3.2 years). The mean awaiting time for
operation was 1.2 months. The Lysholm score was improved from preoperative 42.5
+/- 4.5 (ranged, 33 to 48) to the latest follow-up 78.1 +/- 3.9 (ranged, 57 to
95). The function of knee joint was improved obviously in the arthroscopic
reconstruction patients, with joint range of motion exceeding 900 and with Varus
& Valgus tests near to normal. All the patients had negative findings in the
Lachman test at 70 degrees of flexion. CONCLUSION: Arthroscopic reconstruction
should be the first choice in treating multiple ligament injuries of knee joints.
If the anterior and posterior cruciate ligament injuries can't be treated
simultaneously, the posterior cruciate ligament injuries should be treated
preferentially at the first stage and the anterior cruciate ligament injuries
should be treated at the second stage. The diagnosis of posterior cruciate
ligament is easy to be missed.
PMID- 27505965
TI - [Diagnostic analysis of the radiologic characteristics in osteoporotic Kiinmmel's
disease].
AB - OBJECTIVE: To explore the diagnostic value of the radiologic characteristics of
osteoporotic Kummell's disease. METHODS: Total 16 patients with pathologically
confirmed osteoporotic Kummell's diseases were reviewed from May 2010 to May
2012, including 4 males and 12 females with the mean age of 73.4 years (ranged,
67 to 83 years old). Radiologic imagings of all patients, including X-ray, CT and
MRI, were analyzed retrospectively. RESULTS: Intravertebral linear clefts could
be seen on the AP and lateral X-ray films of vertebrae. Sagittal and axial CT
scans demonstrated the vacuum cleft phenomenon with liquid and air was identified
within the vertebral body. Sagittal MRI showed the callapsed vertebral segment
and the area of fluid signal with clear and intact border within the vertebral
body. The fluid signal was low on T1-weighted images and high on T2-weighted
images and stir images, which was corresponding to an intravertebral vacuum
cleft. CONCLUSION: The radiologic characteristics of Kurmmell's diseases can
provide valuable evidences for the early diagnosis.
PMID- 27505966
TI - [Clinical effects of arthroscopic reconstruction of anterior cruciate ligament
and minimally invasive reconstruction of posteromedial corner].
AB - OBJECTIVE: To evaluate the clinical effects of arthroscopic reconstruction of
anterior cruciate ligament (ACL) and minimally invasive reconstruction of
posteromedial corner (PMC). METHODS: There were 22 cases of ACL and PMC tear were
performed with reconstruction from March 2012 to February 2014. The patients were
29.4 years old on average, including 8 males and 14 females. ACL reconstruction
was performed under arthroscopy and PMC reconstruction was performed minimally
invasively through the ACL incision. The stability of knee was assessed by
anterior drawer test,Lachman test,vulgus stress test and Slocum test. The
function of knee was assessed by Lysholm score and Tegner activity rating. MRI of
knee was checked 12 months after operation. RESULTS: The stability tests of all
patients were negative at 2 and 6 months after operation, and there was one
positive case in anterior drawer test and another positive case in vulgus stress
test at 12 months after operation. Lysholm score of all patients 12 months after
operation was 96.8 +/- 6.8, which was significantly better than 32.0 +/- 11.2
before operation. Tegner activity rating of all patients at 12 months
postoperatively was 6.1 +/- 0.9, which was significantly better than 0.9 +/- 0.5
before operation. It showed the grafts were very well in the MRI 12 months
postoperatively. CONCLUSION: Arthroscopic ACL reconstruction and minimally
invasive PMC reconstruction can restore the stability of knee.
PMID- 27505967
TI - [Application of a self-made steel wire guide in the treatment of avulsion
fractures of tibial posterior cruciate ligament].
AB - OBJECTIVE: To explore the effect of a self-made guiding needle of steel wire in
guiding the wire through the tibial tunnel for the treatment of avulsion
fractures of tibial posterior cruciate ligament with open reduction and wire
fixation. METHODS: From February 2011 to June 2014, a total of 22 patients with
avulsion fractures of tibial posterior cruciate ligament underwent surgical
treatments were analyzed, including 14 males and 8 females with an average age of
35.6 years old (ranged, 17 to 63 years old). According to Meyers classification,
9 patients were classified as type II, 13 patients were classified as type III.
All the patients underwent open reduction and wire fixation with medial knee "L"
shape approach. A wire guiding needle was used to guide the wire through the
tibial tunnel during operation. RESULTS: With the assistance of wire guidance
needles, wires passed through the tibial tunnel rapidly during the operation in
all the 22 patients. All the patients were followed up, X-ray imagings 6 months
after operation showed the fractures healed well. The average follow-up time in
all patients was 6 months (ranged, 6 to 12 months). The averaged Lysholm knee
score in 22 knee was 92.7 +/- 3.4. All patients' posterior drawer test were
negative. CONCLUSION: Self-made wire guiding needle can simplify the operation
procedures in which the wires pass through the tibial tunnel, shorten the
operation time, reduce the surgical trauma and complications, and be worthy of
clinical application.
PMID- 27505968
TI - [Reconstruction of complex proximal tibial defects using the long-stem tibial
component combined with metallic wedge].
AB - OBJECTIVE: To investigate results of total knee arthroplasty using the long-stem
tibial component combined with metallic wedge of knee prosthesis for the
treatment of proximal defects. METHODS: From January 2011 to May 2013, 10
patients (11 knees) were treated with total knee arthroplasties using the long
stem tibial component with metallic tibial wedge of knee prosthesis. All the
patients were female and the average age was 67 years old (ranged, 60 to 77 years
old). All the patients were osteoarthritis. All the patients were classified as
T2A style. The patients were evaluated according to knee score system (KSS).
RESULTS: All the patients were followed up for 12 months on average (ranged 3 to
29 months). The clinical outcome was assessed using KSS score, including knee
pain score, knee stability score, knee range of motion score and knee walking
score, knee stairs score. There were significantly differences at 6 weeks, 3
months, 6 months and 12 months between pre-and postoperative KSS score.
CONCLUSION: The mechanical stability of tibial fixation in primary TKA is
significantly increased by using the long-stem tibial component with metallic
wedge of knee prosthesis, even in the presence of poor proximal bone.
PMID- 27505969
TI - [A case report in entrapment of the ulnar nerve by forearm deep flexor tendon
ganglion cyst].
PMID- 27505970
TI - [Microdecompression for intraforaminal lumbar disc herniations].
AB - OBJECTIVE: To summarize clinical results of the microdecompression for the
treatment of intraforaminal lumbar disc herniations. METHODS: From September 2005
to May 2013,16 patients( 12 males, 4 females)with intraforaminal lumbar disc
herniations underwent microdecompression, ranging in age from 32 to 56 years old
with a mean of 38.6 years old. The lumbar disc herniations were located at
L(3,4). in one patient, L(4,5) in 10 cases and L5S1 in 5 cases. RESULTS: All the
patients were followed up, and the duration ranged from 20 to 48 months, with a
mean period of 36 months. According to Macnab evaluation, 12 cases got an
excellent result, 4 good. No apparent complications related to the technique
occurred. Satisfactory clinical results were obtained in this series. CONCLUSION:
Microdecompression may be particularly useful in the treatment of intraforaminal
lumbar disc herniations. The microdecompression procedures are more likely to be
well tolerated by older patients.
PMID- 27505971
TI - [A review of research on the application of small intestinal submucosa in
repairing osteoarticular injury].
AB - The ideal treatment and recovery of osteoarticular injury remain to be resolved.
Small intestinal submucosa (SIS), a naturally-occurring decellularized
extracellular matrix, has been recognized as an ideal scaffold for tissue
engineering and widely used in repairing various tissues and organs. Nowadays its
application has also been gradually increased in the field of orthopedics. We
reviewed laboratorial studies and clinical trails about the application of SIS in
bone and joint repair, aiming to evaluate its effects on the repair of bone,
cartilage, meniscus, ligament and tendon. SIS has showed promising results in
repairing bone, meniscus, ligament or tendon. However, additional studies will be
required to further evaluate its effects on articular cartilage and tendon-bone
healing. How to optimize SIS material,is also a focused problem concerned with
making SIS a potential therapeutic option with high value for orthopedic tissue
repair.
PMID- 27505972
TI - 11 STRATEGIES FOR A SUCCESSFUL MERGER.
PMID- 27505973
TI - USE DATA IN DIGITAL MARKETING.
PMID- 27505974
TI - PEERS BENEFIT FROM ADVANCED TRAINING.
PMID- 27505976
TI - 5 SKILLS EVERY EXECUTIVE MUST HAVE.
PMID- 27505975
TI - ROSECRANCE AT 100.
PMID- 27505977
TI - 5 WAYS TO MODERNIZE THE BUSINESS SIDE OF YOUR BUSINESS.
PMID- 27505978
TI - HOW TO REDUCE WORKPLACE VIOLENCE.
PMID- 27505979
TI - MENTAL HEALTH FIRST-AID TOOLS IN DEMAND.
PMID- 27505980
TI - RESEARCHER UNCOVERS TRENDS IN MENTAL HEALTH DISPARITIES.
PMID- 27505981
TI - IT'S TIME TO MOBILIZE mHEALTH IN BEHAVIORAL HEALTHCARE.
PMID- 27505982
TI - WHAT WORKS: CLOUD COMPUTING.
PMID- 27505983
TI - WHAT TO DO IF A BREACH HAPPENS TO YOU.
PMID- 27505984
TI - WHY YOUR CLAIMS ARE BEING REJECTED.
PMID- 27505985
TI - NORTH TAMPA BEHAVIORAL HEALTH. Wesley Chapel, Florida.
PMID- 27505986
TI - Prevention of caries with probiotic bacteria during early childhood. Promising
but inconsistent findings.
AB - PURPOSE: This review summarized the available literature on the prevention of
childhood caries through biofilm engineering with probiotic bacteria in early
childhood. METHODS: Three databases (PubMed, Cochrane Library and Trip) were
searched through January, 2016 for randomized controlled trials published in
English. Out of 144 abstracts, seven studies fulfilled the predetermined
inclusion criteria and were quality assessed with respect to risk of bias
independently by two examiners. Due to the paucity and heterogeneity, a narrative
synthesis was performed. The effect size was estimated from the caries prevalence
and expressed as prevented fraction and number needed to treat. RESULTS:
Probiotic supplements were better than placebo in preventing early childhood
caries in all seven studies although the difference was statistically significant
in only four of them. The prevented fraction ranged from 11% to 61% with a median
of 48%. However, the quality of the evidence was low or very low and further
translational research is needed to investigate this preventive approach in the
clinic.
PMID- 27505987
TI - A spectroscopic and surface microhardness study of enamel exposed to beverages
supplemented with ferrous fumarate and ferrous sulfate. A randomized in vitro
trial.
AB - PURPOSE: To compare the efficacy between supplementing ferrous fumarate and
ferrous sulfate to carbonated beverages by recording the in vitro mineral loss
and surface microhardness (SMH) changes in human enamel. METHODS: 120 enamel
blocks each (from primary and permanent teeth) were uniformly prepared and the
initial SMH was recorded. These enamel specimens were equally divided (n = 60)
for their respective beverage treatment in Group 1 (2 mmol/L ferrous sulfate) and
Group 2 (2 mmol/L ferrous fumarate). Each group was further divided into three
subgroups as Coca-Cola, Sprite and mineral water (n= 10). The specimens were
subjected to three repetitive cycles of respective treatment for a 5-minute
incubation period, equally interspaced by 5-minute storage in artificial saliva.
The calcium and phosphate released after each cycle were analyzed
spectrophotometrically and the final SMH recorded. RESULTS: The results were
tested using student's t-test, one-way ANOVA and Wilcoxon signed rank test (P <
0.05). The spectrophotometric assessment of calcium and phosphate withdrawal
found more loss with the supplementation of 2 mmol/L ferrous sulfate than ferrous
fumarate (P < 0.005). Similarly, the mean surface microhardness reduction was
less with the supplementation of 2 mmol/L ferrous fumarate than with ferrous
sulfate (P < 0.005). Statistical comparisons revealed the maximum surface
microhardness and mineral loss with primary enamel and the maximum loss produced
in all groups by Coca-Cola (P < 0.005).
PMID- 27505988
TI - Health concerns of heterotrophic plate count (HPC) bacteria in dental equipment
water lines.
AB - There is an unsubstantiated concern as to the health relevance of HPC
(heterotrophic plate count) bacteria in dental equipment waterlines. The American
Dental Association (ADA) web site includes guidelines for controlling HPC
populations and implies that HPC populations >500 CFU/mL as a "health" benchmark.
The world-wide published literature including the United Nations fully examined
this situation and concluded that HPC bacteria are not a health risk, but merely
a general water quality parameter for all waters including dental water lines.
This review provides documentation that the standard measurement of HPC bacteria
in waters alone do not pose a health risk and the ADA already provides
appropriate practices to minimize HPC bacteria in dental equipment water.
PMID- 27505989
TI - Potential of desensitizing toothpastes to reduce the hydrogen peroxide diffusion
in teeth with cervical lesions.
AB - PURPOSE: To evaluate the occlusive potential of four toothpastes by atomic force
microscopy (AFM) before and after bleaching and quantify the hydrogen peroxide
(HP) diffusion into the pulp chamber after application of desensitizing
toothpastes in teeth with cervical lesions. METHODS: In 52 human extracted
premolars, 2-mm deep artificial cervical lesions (ACL) were prepared and rinsed
with EDTA for 10 seconds. Then teeth were adapted in a brushing machine and
brushed with one of the following toothpastes [Regular toothpaste with no
occlusive compounds Colgate Cavity Protection (CP), Oral-B Pro Health (OB),
Colgate ProRelief (PR) and Sensodyne Rapid Relief (RR)] under constant loading
(250 g; 4.5 cycles/seconds; 3 minutes). In 13 teeth (control group), no
artificial cervical lesion was prepared. After that, the teeth were bleached with
35% HP with three 15-minute applications. The HP diffusion was measured
spectrophotometrically as a stable red product based on HP reaction with 4
aminoanthipyrine and phenol in presence of peroxidase, at a wavelength of 510 nm
and the dentin surfaces of ACL were evaluated before and after bleaching by AFM.
Data was statistically analyzed by one-way ANOVA and Tukey's test (alpha = 0.05).
RESULTS: In the AFM images, some modifications of the dentin surface were
observed after application of OB and RR. However, only for RR the formation of a
surface deposit was produced, which occluded the majority of the dentin tubules.
Also, only for RR, this deposit was not modified/removed by bleaching. Despite
this, all groups with ACL showed higher HP penetration than sound teeth,
regardless of the toothpaste used (P < 0.001).
PMID- 27505990
TI - Consumption of baked nuts or seeds reduces dental plaque acidogenicity after
sucrose challenge.
AB - PURPOSE: To assess the acidogenic potential of eight different types of baked
nuts or seeds eaten alone and after a sucrose challenge using in-dwelling
electrode telemetry. METHODS: Six participants wearing a mandibular partial
prosthesis incorporated with a miniature glass pH electrode were enrolled. The
plaque pH was measured after 5 or 6 days of plaque accumulation. To establish a
control, the subjects were instructed to rinse with sucrose, without any
subsequent treatment, at the first visit. At each subsequent test visit, the
subjects were asked to chew sugar free xylitol gum or consume 10 g of baked (180
degrees C, 5 minutes) peanuts, walnuts, pistachios, cashews, almonds, sunflower
seeds, pumpkin seeds, or watermelon seeds alone and 10 minutes after a sucrose
rinse. The minimum plaque pH value and area of plaque pH curve under 5.7 (AUC5.7)
during and after nut/seed consumption or gum chewing alone, the plaque pH value
at 10 minutes after the sucrose rinse, the time required for the pH to return to
>5.7 and AUC5.7 after the sucrose rinse with or without nut/seed consumption or
gum chewing were calculated from the telemetric curves. RESULTS: The sucrose
rinse induced a rapid decrease in the plaque pH to 4.32 +/- 0.17 at 10 minutes;
this value remained below 5.7 for the measurement period. The AUC5.7 values were
34.58 +/- 7.27 and 63.55 +/- 15.17 for 40 and 60 minutes after the sucrose
challenge, respectively. With the exception of cashews and pumpkin seeds (minimum
pH, 5.42 and 5.63 respectively), the nuts or seeds did not decrease the plaque pH
to below 5.7 when consumed alone, with the AUC5.7 values during and after
consumption (total 40 minutes) ranging from 0.24 to 2.5 (8.44 for cashews), which
were significantly lower than those after the sucrose challenge. Furthermore,
nut/seed consumption or gum chewing after the sucrose challenge significantly
reversed the sucrose-induced decrease in the plaque pH, and the time required for
the pH to return to >5.7 and the AUC5.7 values for 60 minutes after the sucrose
challenge were much less than that of the sucrose challenge without subsequent
interference.
PMID- 27505991
TI - Antimicrobial efficacy of complete denture cleansers.
AB - PURPOSE: To evaluate the in vitro antimicrobial efficacy of alkaline peroxides
against microbial biofilms on acrylic resin surfaces. METHODS: Denture base
acrylic resin (Lucitone 550; n= 360) circular specimens (15 x 3 mm) were obtained
from a circular metal matrix and sterilized with microwave irradiation (650 W, 6
minutes). The specimens were then contaminated with suspensions [106 colony
forming units (CFU)/mL] of Candida albicans (Ca), Candida glabrata (Cg),
Staphylococcus aureus (Sa), Streptococcus mutans (Sm), Bacillus subtilis (Bs),
Enterococcus faecalis (Ef), Escherichia coli (Ec), and Pseudomonas aeruginosa
(Pa). After contamination, the specimens were incubated at 37 degrees C for 48
hours and then placed in a stainless steel basket, which was immersed in a beaker
with one of the following solutions prepared and used according to the
manufacturers' instructions (n= 10 per group): Group PC (positive control),
phosphate-buffered saline (PBS) solution; Group MI, NitrAdine, Medical
Interporous; Group EF, Efferdent Plus; Group CT, Corega Tabs; and Group NC
(negative control; n= 5), no contamination and immersed in PBS. After incubation
(37 degrees C, 24 hours), the number of colonies with characteristic morphology
was counted, and CFU/mL values were calculated. The data were processed following
the transformation into the formula log" (CFU + 1) and statistically analyzed by
the Kruskal-Wallis and Dunn's tests (alpha = 0.05). RESULTS: There were
significant differences between the groups for the evaluated microorganisms with
a significant reduction in the CFU/mL. MI was effective for Ca, Cg, Sa, Sm, Ef,
Ec and Pa; EF was effective for Cg, Sm, Ef, Ec and Pa; and CT was effective for
Sa, Bs and Ec, when compared with the PC group.
PMID- 27505992
TI - Effect of mechanical toothbrushing combined with different denture cleansers in
reducing the viability of a multispecies biofilm on acrylic resins.
AB - PURPOSE: To investigate the efficacy of immersion and brushing with different
cleansing agents in reducing the viability of multispecies biofilm on acrylic
resins. METHODS: Lucitone 550 (L) and Tokuyama Rebase Fast II (T) specimens (10 x
2 mm) were prepared, sterilized, and inoculated with a suspension of Candida
albicans, Candida glabrata, and Streptococcus mutans. Specimens were incubated
for 48 hours at 37 degrees C for biofilm formation. Then, they were divided into
groups (n = 12) and subjected to brushing or immersion for 10 seconds in
distilled water (W), 0.2% peracetic acid-Sterilife (Ac), 1% chlorhexidine
digluconate (CHX), 1:1 water/dentifrice solution (D), 1% sodiumhypochlorite
(NaOCl), and sodium perborate/Corega Tabs (Pb). Viable microorganisms were
evaluated by the XTT assay and colony counts (cfu/mL). Data were performed by
ANOVA and Tukey test with 5% significance level. RESULTS: The multispecies
biofilm on L and T were killed by brushing or immersion in Ac, CHX, and NaOCl for
only 10 seconds.
PMID- 27505993
TI - Headache and jaw locking comorbidity with daytime sleepiness.
AB - PURPOSE: To investigate the relationship between craniofacial pain symptoms
(painful conditions present in the cranium and face, including jaw joint-related
pathology and primary headache conditions) and daytime sleepiness, determined by
the Epworth sleepiness scale (ESS), to correlate comorbidity as well as potential
predictive factors. METHODS: 1,171 patients seeking care for chronic pain and/or
sleep-related breathing disorders (SRBDs) at 11 international treatment centers
were included in the study. Patients completed the ESS and identified their
primary craniofacial pain and sleep pathology symptoms. Descriptive statistics
and regression analysis were performed to determine comorbidities between
craniofacial pain symptoms and daytime sleepiness, and factors predictive of
higher ESS scores. RESULTS: There was high comorbidity of some craniofacial pain
symptoms and high ESS scores, including headaches. In addition, for the first
time to our knowledge, orthopedic craniofacial dysfunction (i.e., jaw locking)
was correlated with, and predictive of, high ESS scores.
PMID- 27505994
TI - An ion extract obtained from mineral trioxide aggregate induced dentin
remineralization and dentin tubule occlusion in artificially demineralized bovine
dentin.
AB - PURPOSE: To investigate the ability of a mineral trioxide aggregate (MTA) extract
mixed with a phosphate buffered saline (PBS) system to induce remineralization
and dentin tubule occlusion in artificially demineralized bovine dentin. METHODS:
The MTA extract solution was prepared by mixing white ProRoot MTA with distilled
water (1:2) for 48 hours, before subjecting it to centrifugation. The elemental
composition of the MTA extract solution was analyzed with inductively coupled
plasma atomic emission spectrometry. The deposits produced by the MTA extract-PBS
mixture were chemically analyzed using electron probe microanalysis (EPMA) and X
ray diffraction (XRD). The effects of the two-step application of the mixture
(MTA extract solution followed by PBS) to bovine dentin samples that had been
artificially demineralized with phosphoric acid (10%, 10 seconds) were
investigated with scanning electron microscopy and EPMA after the specimens had
been stored in PBS for 1 or 7 days. RESULTS: The MTA extract solution contained
calcium, silicone, and aluminum (Ca>Si>Al), and the deposits produced by the MTA
extract-PBS mixture contained calcium, phosphorous, sodium, silicone, and
aluminum (Ca>P>Na>Si>Al) as major mineral elements. XRD also revealed that the
deposits contained hydroxyapatite. The two-step application process resulted in
the formation of a 2-3 microm-thick "mineral infiltration layer", together with
mineral tag-like structures in the dentin tubules. The MTA extract-treated
specimens exhibited a significantly higher dentin tubule occlusion rate than the
untreated specimens (P < 0.05).
PMID- 27505995
TI - Wear of an enhanced resin-modified glass-ionomer restorative material.
AB - PURPOSE: To compare the wear of an enhanced resin-modified glass-ionomer (RMGI)
restorative material (ACTIVA BioACTIVE Restorative) to a resin composite (Filtek
Supreme Ultra), RMGI (Fuji II LC), and glass-ionomer (GI) (Fuji IX) material.
METHODS: Specimens of each material (n = 8) were prepared in a silicone mold. All
specimens other than the GI material were light polymerized for 40 seconds. After
24-hour storage (H2O, 37 degrees C), the specimens were loaded into the modified
Alabama wear testing device. Freshly extracted cusps of human premolars were
prepared as antagonists. Specimens were loaded with 20N for 100,000 cycles at 1
Hz. A 33% glycerin lubricant was cycled throughout testing. Specimens and enamel
antagonists were scanned before and after wear testing with a non-contact optical
profilometer and volumetric wear was measured with superimposition software.
Representative specimens were examined with scanning electron microscopy. Data
were analyzed with a 1-way ANOVA and Tukey post-hoc analysis (alpha = 0.05).
RESULTS: Significant differences were found between materials. Materials ranked
in order of increasing wear: Filtek Supreme Ultra and ACTIVA BioACTIVE
Restorative < Fuji II LC < Fuji IX. Micrographs revealed that Filtek Supreme
Ultra and ACTIVA BioACTIVE Restorative underwent abrasive wear whereas Fuji II LC
and Fuji IX underwent fatigue wear.
PMID- 27505996
TI - Bond strength of resin cements to dentin using universal bonding agents.
AB - PURPOSE: To determine the effect of new universal bonding agents on the bond
strength of dual-cure resin cements to dentin. METHODS: 140 extracted human third
molars were mounted in dental stone and sectioned with a saw to remove coronal
tooth structure. The teeth were randomly divided into seven groups of 20, based
on the use of five universal bonding agents (All-Bond Universal; FuturaBond U;
Prime&Bond Elect; Scotchbond Universal; Clearfil Universal) compared to two self
etch bonding agents (Clearfil SE Bond and Clearfil SE Bond 2). Each group was
further divided into two equal subgroups of 10 specimens each with each subgroup
tested with either self- or light-cure activation of the dual-cure resin cement
(Calibra). The bonding agent was applied per manufacturers' instructions to the
dentin surface of each specimen. The specimens were placed into a jig and resin
cement was inserted into the mold to a height of 3-4 mm and light cured.
Specimens were stored for 24 hours in 37 degrees C distilled water and tested in
shear in a universal testing machine. A mean shear bond strength value (MPa) and
standard deviation was determined per group. RESULTS: Except for Clearfil
Universal, the new simplified universal bonding agents resulted in significantly
lower shear bond strength of the resin cement to dentin than the two-step, self
etching bonding agents Clearfil SE Bond or Clearfil SE Bond 2.
PMID- 27505997
TI - Intratubular penetration in post cementing: A comparative study between a total
etching system and a self-etching cement.
AB - PURPOSE: To analyze the penetration depth and percentage perimeter with
penetration of two fiber post cementing systems using confocal laser scanning
microscopy (CLSM). METHODS: 20 maxillary incisors were shaped with the Mtwo
system and filled using lateral condensation and TopSeal mixed with fluorescein.
Fiber posts were cemented. The samples were divided into two groups of 10 teeth
each, according to the post cementing technique used: Prime&Bond NT combined with
Rebilda DC using a total dentin etching technique (Group 1); or BisCem a self
adhesive cement (Group 2). Rhodamine B was incorporated in the adhesive systems.
Cross-sections were prepared, with the selection of three sections (coronal,
middle and apical thirds). CLSM was used to measure the percentage perimeter of
the root canal showing penetration of the endodontic cement and of the adhesive
system in the dentin tubules, together with the maximum penetration depth. The
nonparametric Mann-Whitney U-test was used to compare the data referred to each
of the three tooth sections between the two study groups. The Friedman test was
used to compare the variables by coronal, middle and apical thirds within each
group. RESULTS: Greater penetration was recorded with the BisCem system in all
thirds, with statistically significant differences in the case of the middle and
apical thirds (P = 0.001). The percentage perimeter with penetration was also
greater in all thirds with the BisCem system, though without significant
differences between the two groups. Penetration depth and percentage were found
to decrease in the coronal to apical direction in both groups.
PMID- 27505998
TI - PUBLIC FUNDING FOR DENTAL CARE.
PMID- 27505999
TI - Knowledge, opinions and factors influencing practices regarding sugar in oral
paediatric medications: a survey of Dunedin pharmacy staff.
AB - BACKGROUND AND OBJECTIVES: Sugar, a known aetiological factor in dental decay,
has been used in paediatric medications as a bulking agent, preservative and to
improve taste. Although artificial sweeteners have largely replaced sugar, some
prescribed and over-the-counter (OTC) paediatric medications and supplements
containing sugar are still available in New Zealand. Little is currently known
about the knowledge, opinions and practices of staff in NZ pharmacies regarding
sugar-containing paediatric medications. This study was carried out to
investigate these factors. METHODS: After ethical approval was obtained,
questionnaires were delivered to all staff members at pharmacies in the greater
Dunedin area. Quantitative statistical analysis was carried out using SPSS
version 22.0 with the alpha value set at 0.05. Qualitative data were analysed
using a general inductive technique. RESULTS: A total of 58 questionnaires were
returned giving a pharmacy response rate of 63.0%. Some 29.9% of respondents
thought the inclusion of sugar in medications necessary and 77.6% agreed that
sugar in paediatric medications can contribute to dental decay. Most of the 67.2%
who reported that they do not give advice to customers regarding sugar in
medications and oral health, felt it was not a priority. Parental request was the
main factor determining provision or recommendations regarding sugar-free options
(87.9%). CONCLUSION: Although choice of a sugar-free medication can be limited by
many factors, inter-professional collaboration and knowledge sharing on this
topic would be advantageous. In addition, the provision of more formalised
education, either as part of undergraduate pharmacy curricula or as part of
continuing education, should be considered.
PMID- 27506000
TI - A review of occupationally-linked suicide for dentists.
AB - BACKGROUND AND OBJECTIVES: Suicide rates among dentists and a perceived elevated
risk for suicide have been debated in the academic literature. It has filtered
into the public psyche that dentists have the highest suicide rate of any
occupation. The present review seeks support for both protagonist and antagonist
positions from multidisciplinary perspectives. Contemporary risk factors and
strategies for intervention and the prevention of suicide in dentistry are
explored. METHODS: An online database search for articles and reports, with
selected target words, was conducted for peer reviewed publications on suicide in
the dental profession, and for factors contributing to dentist suicide. Review
guidelines from the American Psychological Association were used to clarify
concepts, identify where most work was focussed, and to explore the superiority
of any approach to the emotive topic over another. RESULTS: Findings suggest the
dominant belief that dentists have an elevated risk of suicide may be
historically, but not currently, accurate. Although dentists' suicide is trending
down, diversity in methodology means no current consensus is possible. Factors
found to be influencing dentists' suicide ranged from known occupational
stressors, to toxins and substance abuse, and untreated mental health problems.
CONCLUSION: The contemporary position in New Zealand shows dentists per se are
not more likely than other health professionals to commit suicide although they
may have been in the past. Dentists should be aware of individual susceptibility
to burnout and mental health problems. Future directions are outlined to address
this including peer intervention, and programmes available for dentists to cope
better with risks leading to suicide.
PMID- 27506001
TI - Dental implant use in New Zealand: A 10-year update.
AB - OBJECTIVE: The aim of this study was to explore changes in dentists' promotion
and use of implants in New Zealand over the past 10 years. METHODS: A postal
survey was conducted of a random sample of 807 New Zealand registered dentists,
using a 23-item questionnaire adapted from one used in a similar survey in 2004.
RESULTS: The participation rate was 54.3%. In the past 10 years, the percentage
of dentists providing an implant service has increased from 49.4% to 68.0%, with
an equal proportion of females now providing this service. Single missing teeth
(56.9%) and trauma (51.5%) are the most common clinical situations in which
implants are provided. Patient enquiries about implants have slightly increased.
A need for continuing education, particularly in the area of implant prosthetic
procedures, was noted by 76.5%. Despite more proprietary implant systems now
being available, the most commonly used system has remained unchanged. Cost is
still the primary barrier to implementing implant treatment. CONCLUSIONS:
Although dental implant use in New Zealand has increased, it appears that a need
exists for continuing education, particularly for implant prosthetic procedures.
The perceived expense of treatment continues to hinder optimal utilisation.
PMID- 27506002
TI - Ethnic and socioeconomic inequalities in dental treatment at a school of
dentistry.
AB - BACKGROUND AND OBJECTIVES: Health services should be targeted toward those most
in need of health care. Poor oral health disproportionately affects Maori,
Pacific Island, and socioeconomically deprived New Zealanders of all ages, and
oral health care services should be prioritised to such groups. In New Zealand,
free oral health care is available for all children up to the age of 17. On the
other hand, adult dental services are provided on a user-pays basis, except for a
limited range of basic services for some adults, access to which varies
regionally. This study investigated the extent of dental treatment inequalities
among patients at New Zealand's only School of Dentistry. METHODS: Data were
audited for all treatments provided at the University of Otago Faculty of
Dentistry from 2006 to 2011 for patients born prior to 1990. Ethnic and
socioeconomic inequalities in the provision of dental extractions, endodontic
treatment, crowns, and preventive care were investigated. Differences were
expressed as the odds of having received one or more treatments of that type
during the six-year period 2006 to 2011. RESULTS: Data were analysed for 23,799
individuals, of whom 11,945 (50.2%) were female, 1,285 (5.4%) were Maori and 479
(2.0%) were Pacific, 4,040 (17.0%) were of low socioeconomic status (SES), and
2,681 (11.3%) were beneficiaries or unemployed. After controlling for SES, age,
and sex, Maori had 1.8 times greater odds of having had a tooth extracted than NZ
European patients, while Pacific Islanders had 2.1 times the odds. Furthermore,
after controlling for ethnicity, age, and sex, low-SES patients had 2.4 times
greater odds of having had a tooth extracted than high-SES patients, and
beneficiaries had 2.9 times the odds. Conversely, these groups were less likely
to have had a tooth treated with a crown or endodontics or receive preventive
care. CONCLUSIONS: Existing policies call for the reduction of inequalities.
There is a need for a strategy to monitor changes in treatment inequality over
time which includes improving equity in service care provision. The observed
treatment inequalities are likely to be an underestimate of those occurring in
private dental practice in New Zealand.
PMID- 27506003
TI - LAWRENCE J CROXSON, ONZM.
PMID- 27506004
TI - Eliminating Leprosy in India--Is it a Dream?
AB - In recent years there have been considerable discussions on the current leprosy
situation in India and the status of the country's attempts to eliminate or
eradicate the disease. In this connection it is very important to analyze the
background and various developments relevant to leprosy elimination in India.
PMID- 27506005
TI - Study of 35 Cases of Hansen's Disease, which Required Treatment beyond Fixed
Duration--Multi Drug Therapy.
AB - Multi Drug Therapy (MDT) is the main weapon against leprosy since its inception
in 1981. India achieved the level of elimination (< 1 case/10,000) on 31st
December 2005. It has been proved in few studies that despite 2 years of regular
therapy 10% of the patients continue to harbour viable persisters. There are many
problems related with FD-MDT. Many cases have residual disease activity after
completion of treatment. Aims of the present study was to study the profile of
RFT cases in leprosy treated with FD-MDT, who required extended MDT, duration
between completion of FD -MDT and clinical presentation, Acid Fast Bacilli (AFB)
status, histopathology and type of leprosy at the time of presentation. A
prospective study of 35 RFT (Released FromTreatment) cases with signs of activity
were recruited in period betveen May 2007 to November 2001. All cases were
diagnosed clinically and investigations were done for AFB smear,
histopathological examination and Fite Faraco staining. We found that all the 35
cases, which required extended MDT, age group ranged from 10 to 65 years.
Majority (71.4%) had taken previous Multi-Bacillary (MB) treatment for 1 year
duration. Eleven (31.42%) of cases came within one year, 17 (48.57%) between one
to two years and 7 (20%) cases after two years of stopping FD-MDT. AFB smear was
positive in 36.84% of cases in which done. Majority of previously diagnosed MB
cases presented as BT/TT in histopathology. Thus there is need to search for
reliable prognostic markers for therapeutic purposes.
PMID- 27506006
TI - A Rare Combination of Pure Neuritic Leprosy with Morphea Leading to Diagnostic
Confusion.
AB - A circumscribed sclerotic plaque of morphea can sometimes be mistaken for
tuberculoid leprosy and vice versa can also happen. However, the co-existence of
a patch of morphea mimicking as Leprosy patch in an underlying case of
neuriticleprosy, can be very misleading. We present a case with glove and
stocking anaesthesia and peripheral nerve enlargement with a single large
hypopigmented, non-anaesthetic macule on trunk, clinically diagnosed as Hansen's
disease (Borderline Tuberculoid - BT). Slit skin smears proved to be negative for
AFB and histopathology of the skin lesion was consistent with morphea, which lead
us to do a nerve biopsy. Sural nerve biopsy proved it to be Hansen's neuritis
with occasional bacilli. The patient was started on MDT-MB and followed up. This
is a rare case of co-existing morphea with Hansen's disease. It would have been
easily misclassified if we had presumed the cutaneous lesion to be a case of
Hansen's (BT) patch and not done a cutaneous nerve biopsy which led to diagnosis
of multibacillary leprosy.
PMID- 27506007
TI - Bone Changes in an Italian Ancient Human Skeleton--Possibly Caused by Leprosy.
AB - Leprosy is an infectious disease caused by Mycobacterium leprae and Mycobacterium
lepromatosis. In the last stage it can afflict the skeleton with a series of
specific and non-specific bone changes. The possibility of studyingthe skeleton
of an individual who lived in the pre-antibiotic era (Roman period) with skeletal
changes in the rhino-maxillary region and hand and foot bones, permitted skeletal
lesions to be analyzed directly. In addition, the localization and the complexity
of the bony lesions could be attributed to the presence of leprosy. The
importance of this approach was the possibility to verify the nature and typology
of the primary and secondary bone changes in leprosy in absence of clinical
therapy.
PMID- 27506008
TI - Histopathological Diagnosis of Leprosy Type 1 Reaction with Emphasis on
Interobserver Variation.
AB - Upgrading typel lepra reaction or reversal reaction (RR) is an acute inflammatory
complication of leprosy and a disparity exists between clinicians and
pathologists for diagnosing a RR. Inter-observer variations among pathologists
also compound this problem as no universally agreed diagnostic criteria exist.
120 biopsies and H&E stained slides were assessed by 3 pathologists. The
pathologists were blinded to the clinical diagnosis and to each other's
observations. Each pathologist assigned a likelihood of reaction by their
histopathological observations as definitely reaction, probable reaction and no
reaction. Clinicopathological correlation and interobserver agreement was
analyzed statistically. Discordance between clinical and histopathological
diagnosis was seen in 30.8% by pathologist 1 (P1), 23.7% by pathologist 2 (P2)
and 34.5% bythe pathologist 3 (P3). Dermal edema, intragranuloma edema and
epidermal erosion were consistent findings by all observers. Definite reaction
was seen in 54.2% of cases by P1, 53.3% by P2 and 34.5% by P3. Kappa statistics
for strength of agreement showed good agreement between 3 pathologists with P1
(kappa = 0.83), P2 (kappa = 0.61), P3 (kappa = 0.62). RR are underdiagnosed on
histopathological examination but this study shows that dermal edema, edema
within the granuloma and partial obliteration of grenz zone by granuloma are
reliable clues to diagnose a RR on histopathology.
PMID- 27506009
TI - [Exploring the Severe Haze in Beijing During December, 2015: Pollution Process
and Emissions Variation].
AB - Severe haze episodes shrouded Beijing and its surrounding regions again during
December, 2015, causing major environmental and health problems. Beijing
authorities had launched two red alerts for atmospheric heavy pollution in this
period, adopted a series of emergency control measures to reduce the emissions
from major pollution sources. To better understand the pollution process and
emissions variation during these extreme pollution events, we performed a model
assisted analysis of the hourly observation data of PM2.5, and meteorological
parameters combined with the emissions variation of pollution sources. The
synthetic analysis indicated that: (1) Compared with the same period of last
year, the emissions of atmospheric pollution sources decreased in December 2015.
However, the emission levels of primary pollutants were still rather high, which
were the main intrinsic causes for haze episodes, and the unfavorable diffusion
conditions represented the important external factor. High source emissions and
meteorological factors together led to this heavy air pollution process. (2)
Emergency control measures taken by the red alert for heavy air pollution could
decrease the pollutants emission by about 36% and the PM2.5 concentrations by 11%
to 21%. Though the implementation of red alert could not reverse the evolution
trend of heavier pollution, it indeed played an active role in mitigation of
PM2.5 pollution aggravating. (3) Under the heavy pollution weather conditions,
air pollutants continued to accumulate in the atmosphere, and the maximum effect
by taking emergency measures occurred 48-72 hours after starting the
implementation; therefore, the best time for executing emergency measures should
be 36-48 hours before the rapid rise of PM2.5 concentration, which requires a
more powerful demand on the accuracy of air quality forecast.
PMID- 27506010
TI - [Pollution Characteristics and Source of HULIS in the Fine Particle During the
Beijing APEC].
AB - In order to investigate the influence of the emission reduction measure during
the Beijing APEC on the concentrations and pollution characteristics of humic
like substances (HULIS) in atmospheric fine particles, PM2.5 samples were
collected and analyzed for OCEC, WSOC, HULIS and water-soluble ions. The
concentration of HULIS in PM2.5 ranged 1 ug . m-3-15 ug . m-3. HULIS
concentrations were 7.99 ug . m-3, 5.83 ug . m-3 and 7.06 ug . m-3 before, during
and after APEC, which indicated emission reduction measure had important effect
on the reduction of HULlS. The decrease of HULIS during the APEC was
significantly faster than those of EC and WSOC, while the increase of HULIS
turned out to be much slower than OC, EC, WSOC and PM2.5 after the meeting. The
proportions of HULIS to PM2.5 were 13.60%, 13.59%, 14.02% and 12.22% at four
different stages, i. e., whole sampling period, before, during and after the
APEC, while HULIS-C/OC and HULIS-C/WSOC were 28.95%, 35.51%, 28.37%, 19.93%; and
52.75%, 59.58%, 51.54%, 45.39%, respectively. HULlS was significantly positively
correlated with humidity, while significantly negatively correlated with wind
speed. Biomass burning and secondary transformation of VOCs might be two
important sources of HULlS in Beijing.
PMID- 27506011
TI - [Seasonal Variation Characteristics and Potential Source Contribution of Sulfate,
Nitrate and Ammonium in Beijing by Using Single Particle Aerosol Mass
Spectrometry].
AB - Single particle aerosol mass spectrometry (SPAMS) was deployed to continuously
observe the aerosol particles of Beijing urban area from 2013-12 to 2014-11, and
the hourly average data of sulfate, nitrate and ammonium (SNA) were obtained
using the characteristic ion tracer method. The mixing state and size
distribution of SNA were analyzed. In addition, based on Hysplit 48 h back air
mass trajectory results in combination with Concentration Weighted Trajectory
method (CWT), we obtained the seasonal potential source contribution area of SNA.
The results showed that the mixture of sulfate, nitrate and ammonium in spring
and summer was more stable than that in autumn and winter. The size distribution
of sulfate and nitrate was very similar. The size distribution characteristics of
SNA followed the order of autumn > summer > spring > winter. The potential source
region of SNA had similar spatial distribution characteristics, and the potential
source region of SNA was mainly located in Beijing and south areas, especially at
Tianjin, Langfang, Hengshui, Baoding and Shijiazhuang.
PMID- 27506012
TI - [Pollution Characteristics and Source Apportionment of PM2.5, in Lanzhou City].
AB - In order to understand the characteristics and sources of PM2.5 pollutant in
Lanzhou City, two PM2.5 sampling sites were set up in Chengguan district and Xigu
district, respectively. Samples were sampled during October (non-heating period)
and December (heating period) 2013, and mass concentrations of PM2.5 and its 16
kinds of chemical components were analyzed. The results showed that the average
mass concentration of PM2.5 during the sampling period was 129 ug . m-3. The
sequence of mass concentrations of inorganic elements was: S > Ca > Fe > Al > Mg
> Pb > Zn > Mn > Ti > Cu, while the mass concentrations of S, Ca, Fe, and Al,
which were the major element compositions, exceeded 1 ug . m-3. The mass
concentration of inorganic elements during heating period was higher than that
during non-heating period, meanwhile, the mass concentration in Chengguan
district was higher than that in Xigu district. The sequence of mass
concentrations of water-soluble ions was: SO42- > NO3- > NH4+ > Cl- > K+ > Na+,
while the mass concentrations of SO42-, NO3-, NH4+, which were the main ion
components, exceeded 10 ug . m-3. The mass concentration of water- soluble ions
during heating period was higher than that during non-heating period, meanwhile,
the mass concentration in Xigu district was higher than that in Chengguan
district. The result of enrichment factor (EF) analysis showed that the EF values
of Al, Ca, Mg and Ti were lower than 1, indicating the contribution of natural
source, while the EF values of Cu, Pb, S and Zn were higher than 10, indicating
the contribution of anthropogenic pollution. The result of principal component
analysis showed that the sources of PM2.5 were mainly derived from traffic
emission, biomass burning, soil and secondary particles.
PMID- 27506013
TI - [Pollution Level and Source Apportionment of Atmospheric Particles PM2.5 in
Southwest Suburb of Chengdu in Spring].
AB - In order to understand the characteristics of PM2.5 pollution in the atmosphere
of Chengdu southwest suburb, PM2.5 particles in Chengdu southwest suburb were
collected and analyzed from March 18 to March 31st, 2015. The results showed that
the daily average concentration of PM2.5 in the southwest suburb of Chengdu
reached 121.21 ug . m-3, and the average daily concentration of 24 samples in 31
PM2.5 samples was over 75 ug . m-3, the daily excessive rate was 77%, indicating
the PM2.5 pollution in the study area was serious in March. When studying the
relationship between atmospheric and meteorological factors, it was found that
there was a significant index correlation between PM2.5 concentration and
atmospheric visibility, and it had a positive correlation with temperature and
humidity, but the correlation was not obvious. NH4+ (16.24%), SO42- (12.58%) and
NO3- (9.91%) were dominant in PM2.5 The ratio of NO3-/SO42- was 0.77, which
indicated that the pollution of stationary sources in the southwest suburb was
more severe than that of mobile sources. Organic carbon (OC)/elemental carbon
(EC) ratios were higher than 2, which indicated the existence of second organic
carbon (SOC). Using OC/EC ratio method to estimate the concentration of SOC, it
was found that the average concentration of SOC in the southwest suburb of
Chengdu in March was 3.49 u . m-3, and the contribution rate of OC was 20.6%,
which showed that the main source of OC in the southwest suburb of Chengdu was
primary discharge. The correlation analysis of OC and EC showed that the
correlation coefficient reached 0.95, indicating that the OC and EC sources were
similar and relatively stable, and there was a great impact of local source
emissions on Chengdu southwest suburb in spring, and primary discharge played a
dominant role, while the contribution of SOC to OC was relatively small, which
was consistent with the SOC characteristics obtained by estimation. Using
principal component analysis method to analyze the sources of PM2.5 in the
southwest of Chengdu, it was found that the main pollution sources of PM2.5 in
southwest suburb of Chengdu were coal burning and biomass burning, secondary
nitrate/sulfate, soil and dust, vehicle emissions, electronic production source,
and mechanical processing source.
PMID- 27506014
TI - [Variation Characteristics of Total Gaseous Mercury at Simian Mountain Background
Station in Mid-subtropical Region].
AB - Total gaseous mercury (TGM) was continuously monitored at the Simian Mountain
Forest Nature Reserve in Chongqing, a representative of the mid-subtropical
region, using high-resolution automatic atmospheric mercury vapor analyzer
(Tekran 2537X) from March 2012 to February 2013. The results showed that the
average concentration of TGM during the monitoring was (2.88 +/- 1.54) ng . m-3,
which was much higher than the background TGM on north hemisphere but lower than
those at most of the other monitoring sites in China. These results suggested
that the TGM level in Simian Mountain was still in the normal range on regional
scale, but had an increasing tendency globally. The TGM level exhibited a
distinct seasonal variation, following the order of winter (3.68 +/- 2.43) ng . m
3 > summer (3.29 +/- 0.79) ng . m-3 > spring (2.44 +/- 0.69) ng . m-3 > autumn
(2.13 +/- 0.97) ng . m-3, and the TGM concentration varied to a greater extent in
winter. The diurnal variation of TGM concentration characterized as being higher
at the nighttime in spring, while higher during the daytime in other seasons. The
concentration variation of TGM had a positive correlation to temperature and
light intensity. The result of backward trajectory analysis using HYSPLIT showed
that the main source of the TGM in Simian Mountain was the local coal combustion,
and long distance transportation by the Indian monsoon might also play a role in
the increasing TGM level.
PMID- 27506015
TI - [Establishment of Method for Health Risk Assessment of Pollutants from Fixed
Sources].
AB - A health risk assessment method of pollutants from fixed sources was developed by
applying AERMOD model in the health risk assessment. The method could directly
forecast the health risks of toxic pollutants from source by some exposure
pathway. Using the established method, in combination with the data of sources
and traditional health risk assessment method as well as the measured data of
PAHs in inhalation particle matter (PM10) in Lanzhou, the health risk of
polycyclic aromatic hydrocarbons (PAHs) and benzo [a] pyrene (BaP) in PM10 from
the three fire power plants and the health risk of PAHs and BaP in PM10 at the
receptor point by inhalation exposure in heating and non-heating seasons was
calculated, respectively. Then the contribution rates of the health risk caused
by the three fire power plants to the health risk at the receptor point were
calculated. The results showed that the contribution rates were not associated
with sex and age, but were associated with time period and risk types. The
contribution rates in the non-heating seasons were greater than those in heating
seasons, and the contribution rates of the carcinogenic risk index were greater
than those of the cancer risk value. The reliability of the established method
was validated by comparing with the traditional method. This method was
applicable to health risk assessment of toxic pollutants from all fixed sources
and environmental risk assessment of environmental impact assessment.
PMID- 27506016
TI - [Testing of Concentration and Characteristics of Particulate Matters Emitted from
Stationary Combustion Sources in Beijing].
AB - A self-built monitoring sampling system on particulate matters and water soluble
ions emitted from stationary combustion sources and a size separated sampling
system on particulate matters based on FPS4000 and ELPI + were applied to test
particulate matters in fumes of typical stationary combustion sources in Beijing.
The results showed that the maximum concentration of total particulate matters in
fumes of stationary combustion sources in Beijing was 83.68 mg . m-3 in standard
smoke oxygen content and the minimum was 0.12 mg . m-3. And particle number
concentration was in the 104-106 cm-3 number of grade. Both mass and number
concentration ranking order of particulate matters emitted from stationary
combustion sources in Beijing was: heating gas fired boilers < power plant coal
fired boilers < heating coal fired boilers. And two or three peaks existed under
1 um of particulate size for both number size distribution and mass size
distribution. The number concentration for PM2.5 accounted for over 99.8% of that
for PM10 and that for PM0.1 accounted for over 83% of that for PM2.5. But the
proportions of PM0.1, and PM2.5 in PM10 were significantly lower in quality
analysis,the proportion of PM2.5 in PM10 was about 82%, and that of PM0.1 in
PM2.5 was about 27%-33%.
PMID- 27506017
TI - [Pollution Evaluation and Risk Assessment of Heavy Metals from Atmospheric
Deposition in the Parks of Nanjing].
AB - Contents of heavy metals involving As, Cd, Cr, Cu, Ni, Pb and Zn from atmospheric
deposition in 10 parks of Nanjing were analyzed. The pollution level, ecological
risk and health risk were evaluated using Geoaccumulation Index, Potential
Ecological Risk Index and the US EPA Health Risk Assessment Model, respectively.
The results showed that the pollution levels of heavy metals in Swallow Rock
Park, Swallow Rock Park and Mochou Lake Park were higher than the others.
Compared to other cities such as Changchun, Wuhan and Beijing, the contents of
heavy metals in atmospheric deposition of parks in Nanjing were higher. The
evaluation results of Geoaccumulation Index showed that Pb was at moderate
pollution level, Zn and Cu were between moderate and serious levels, while Cd was
between serious and extreme levels. The ecological risk level of Cd was high. The
assessment results of Health Risk Assessment Model indicated that there was no
non-carcinogenic risk for all the seven heavy metals. For carcinogenic risk, the
risks of Cd, Cr and Ni were all negligible (Risk < 1 x 10-6), whereas As had
carcinogenic risk possibility but was considered to be acceptable (10-6 < Risk <
10-4).
PMID- 27506018
TI - [CoCuMnOx Photocatalyzed Oxidation of Multi-component VOCs and Kinetic Analysis].
AB - Solar energy absorption coating CoCuMnOx was prepared by co-precipitation method
and applied to photodegrade multi- component VOCs including toluene, ethyl
acetate and acetone under visible light irradiation. The photocatalytic oxidation
performance of toluene, ethyl acetate and acetone was analyzed and reaction
kinetics of VOCs were investigated synchronously. The research indicated that
removal rates of single-component toluene, ethyl acetate and acetone were 57%,
62% and 58% respectively under conditions of 400 mg . m-3 initial concentration,
120 mm illumination distance, 1 g/350 cm2 dosage of CoCuMnOx and 6 h of
irradiation time by 100 W tungsten halogen lamp. Due to the competition among
different VOCs, removal efficiencies in three-component mixture were reduced by
5%-26% as compared with single VOC. Degradation processes of single-component VOC
and three-component VOCs both fitted pseudo first order reaction kinetics, and
kinetic constants of toluene, ethyl acetate and acetone were 0.002, 0.002 8 and
0.002 33 min-1 respectively under single-component condition. Reaction rates of
VOCs in three-component mixture were 0.49-0.88 times of single components.
PMID- 27506019
TI - [Distribution of Nitrogen and Phosphorus in the Tidal Reach and Estuary of the
Daliao River and Analysis of Potential Eutrophication].
AB - Based on the monitoring data in the tidal reach and estuary of the Daliao river
in August and November, 2013, the seasonal and spatial distribution of the
nitrogen and phosphorus forms were studied, and the degree of eutrophication was
evaluated. The results showed that nitrate nitrogen was the main chemical species
and occupied about fifty-five percent of inorganic nitrogen, and the particulate
phosphorus was the main chemical species and occupied about fifty percent of
total phosphorus in the tidal reach and estuary of the Daliao river in wet and
dry seasons, 2013. The concentrations of nitrogen and phosphorus nutrients
decreased in the direction from tidal reach to estuary of the Daliao river.
Correlation analysis showed that there was a significant negative correlation
between the nitrogen and phosphorus forms and salinity in most of the water body,
which illustrated that physical dilution of seawater played a major role in the
spatial distribution of nitrogen and phosphorus forms. The concentrations of
nitrogen and phosphorus nutrients in the dry season were higher than those in the
wet season, this was mainly related to the seasonal terrestrial input of the
tidal reach. The concentration of the dissolved inorganic nitrogen was higher
than 0.30 mg . L-1, and the value of N/P was higher than 60, which indicated that
PO43--P was the nutrient limiting phytoplankton growth in the tidal reach and
estuary of the Daliao river in August and November, 2013.
PMID- 27506020
TI - [Spatial Distribution of Stable Isotope from the Lakes in Typical Temperate
Glacier Region].
AB - We focused mainly on the spatial variation and influencing factors of hydrogen
and oxygen stable isotopes between water samples collected at the surface and
different depths in the Lashi Lake in August, 2014. Hydrological supply
characteristics of the lake in typical temperate glacier region were discussed.
The results showed that the values of delta18O and deltaD in the Lashi Lake
ranged from -12.98 per thousand to -8.16 per thousand with the mean of -9.75 per
thousand and from -99.42 per thousand to -73.78 per thousand with the mean of
82.23 per thousand, respectively. There was a reversed spatial variation between
delta18O and d. Relatively low values of delta18O with high values of d were
found at the edge of the lake where the rivers drained into. Meanwhile, the
values of d in the vertical profile varied little with depth, suggesting that the
waters mixed sufficiently in the vertical direction. The d values increased at
first and then decreased from east to west at different layers, but both increase
and decrease exhibited different velocities, which were related to the river
distribution, the locality of the lake and environmental conditions etc. River
water and atmospheric precipitation were the main recharge sources of the Lashi
Lake, and the melt-water of snow and ice might also be the supply resource. The
delta18O values of lake water in glacier region decreased along the elevation
(except for Lashi Lake), generally, this phenomenon was called "altitude effect".
Moreover, high isotopic values of the lake water from non-glacier region were due
to the evaporation effect.
PMID- 27506021
TI - [delta15N-NO3- and delta18O-NO3- Tracing of Nitrate Sources in Beijing Urban
Rivers].
AB - In order to quantitatively identify sources of nitrate pollution in Beijing urban
area and provide effective guidance for relevant departments to control the
pollution of Beijing rivers, delta15N-NO3- and delta18O-NO3- isotope tracing
method was used to analyze the composition of nitrogen and oxygen stable isotopes
from nitrate in Beijing urban river. Besides, stable isotope mixing model was
adopted to track nitrogen sources of nitrate in Beijing urban rivers and the
contribution rates of respective pollution sources were evaluated. The results
showed that: (1) NO3--N pollution was the main inorganic nitrogen pollution in
Beijing rivers and pollution of downstream was more serious than that of
upstream. (2) delta15N-NO3- in Beijing urban surface rivers was in range of 6.26
per thousand-24.94 per thousand, while delta18O-NO3- ranged -0.41 per thousand
11.74 per thousand; delta15N-NO3- increased from upstream to downstream along the
flow of the surface water. (3) The nitrate pollution composition of Beijing
rivers could be gained from the stable isotope mixing model. The average
contribution rates of manure and sewage, soil nitrate and atmospheric deposition
were 61.2%, 31.5% and 7.3%, respectively.
PMID- 27506022
TI - [Distribution Characteristics and Influencing Factors of Nitrate Pollution in
Shallow Groundwater of Liujiang Basin].
AB - Taking the nitrate in shallow groundwater of Liujiang basin as the research
object, a total of 215 groups of shallow groundwater samples were collected
during the wet period in July 2014 and the drought period in April 2015 on the
basis of groundwater pollution investigation. The characteristics of spatial and
temporal variability and the account of nitrate pollution were analyzed based on
the model of semivariogram, the geostatistics of ArcGIS and factor analysis,
respectively. The results showed that the study region in the southeast was the
main nitrate-polluted area, with concentrations of up to 30-120 mg . L-1, in both
wet and drought periods, while the nitrate-contaminated area in drought period
was about 1. 4 times higher than that in wet period. The spatial distribution of
nitrate was primarily influenced by human activities and the geological
conditions, and secondarily by Eh, DO, pH and landform conditions. The nitrate
concentration was less than 20 mg . L-1 in north. Pollution in local middle area
was rather serious, due to human activities and the loss of nitrogen fertilizer
in agricultural cultivation; the area to the south, which was confined by
impervious boundary, was seriously contaminated, as indicated by the nitrate
accumulation effects.
PMID- 27506023
TI - [Nitrogen Losses Under the Action of Different Land Use Types of Small Catchment
in Three Gorges Region].
AB - As an independent water-collecting area, small catchment is the source of non
point source pollution in Three Gorges Region. Choosing 3 kinds of the most
representative land-use types and using them to lay monitoring points of overland
runoff within the small catchment of Wangjiagou in Fuling of Three Gorges Region,
the author used the samples of surface runoff collected through the twelve
natural rainfalls from May to December to analyze the feature of spatial-temporal
change of Nitrogen's losses concentrations under the influence of different land
use types and the hillslopes and small catchments composed by those land use
types, revealing the relation between different land-use types and Nitrogen's
losses of small catchments in Three Gorges Region. The result showed: the average
losses concentration of TN showed the biggest difference for different land use
types during the period of spring crops, and the average value of dry land was 1.
61 times and 6.73 times of the values of interplanting field of mulberry and
paddy field, respectively; the change of the losses concentration of TN was most
conspicuous in the 3 periods of paddy field. The main element was NO3--N, and the
relation between TN and NO3--N showed a significant linear correlation. TN's and
NO3--N's losses concentrations were significantly and positively correlated with
the area ratio of corn and mustard, but got a significant negative correlation
with the area ratio of paddy and mulberry; NH4+-N's losses concentrations got a
significant positive correlation with the area ratio of mustard. Among all the
hillslopes composed by different land use types, TN's average losses
concentration of surface runoff of the hillslope composed by interplantating
field of mulberry and paddy land during the three periods was the lowest, and the
values were 2.55, 11.52, 8.58 mg . L-1, respectively; the hillslope of rotation
plough land of corn and mustard had the maximum value, and the values were 27.51,
25.11, 27.11 mg . L-1, respectively; different land use types and spatial
combination ways of subcatchment had a greater influence on TN's losses
concentrations, so using a reasonable way to adjust land use structure and
spatial arrangement of whole catchment was an effective measure to control the
source of non-point source pollution of Three Gorges Region.
PMID- 27506024
TI - [Interception Effect of Ecological Ditch on Nitrogen Transport in Agricultural
Runoff in Subtropical China].
AB - Interception effects of an ecological ditch, used to control agricultural non
point source pollution in subtropical China, on nitrogen transport in surface
runoff were studied by monthly measuring the runoff volume and concentrations of
ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3--N) and total nitrogen (TN) at
the ditch inlet and outlet from 2013 to 2014. In addition, differences of NH4+-N,
NO3--N and TN removal were compared between 2013 and 2014. The results showed
that the study ecological ditch worked effectively in N removal with average NH4+
N, NO3--N and TN removal rates of 77.8%, 58.3%, and 48.7%; and their interception
rates were 38.4, 59.6, and 171.1 kg . a-1, respectively. The average proportion
of NH4+-N and NO3--N in TN was 47.5% at inlet, and 33.6% at outlet, which was
significantly lower than that at inlet (P < 0.01). All hydrophytes in the
ecological ditch were replaced by Myriophyllum aquaticum in 2014, which led to
the increased average NO3--N and TN removal rates of 30.5% and 18.2%,
respectively, Compared to in 2013. The vegetation of Myriophyllum aquaticum was
beneficial to the improvement of N interception in ecological ditch. These
findings clearly demonstrated that ecological ditch can substantially reduce N
loss from surface runoff and be used as an important technique to prevent
agricultural non-point N pollution.
PMID- 27506025
TI - [Biodegradation Coefficients of Typical Pollutants in the Plain Rivers Network].
AB - Biodegradation is a significant part of pollutant integrated degradation, the
process rate of which is represented by the biodegradation coefficient. To
investigate the biodegradation law of typical pollutants in the plain rivers
network located in the upstream of the Lake Taihu, experiments were conducted in
site in September 2015, one order kinetics model was used to measure the
biodegradation coefficients for permanganate index, ammonia, total nitrogen and
total phosphorus, and influencing factors of the biodegradation coefficients were
also analyzed. The results showed that the biodegradation coefficients for
permanganate index, ammonia, total nitrogen and total phosphorus were 0.008 3
0.126 4 d-1, 0.002 1-0.213 8 d-1, 0.002 1-0.090 5 d-1 and 0.011 0- 0.152 8 d-1,
respectively. The influencing factors of the biodegradation coefficients for
permanganate index were permanganate index and pH; those for ammonia were ammonia
concentration and pH; those for total nitrogen were inorganic nitrogen
concentration, total dissolved solid concentration and nitrite concentration; and
those for total phosphorus were background concentration and pH. The research
results were of important guiding significance for pollutants removal and
ecological restoration of the plain rivers network located in the unstream of the
Lake Taihu.
PMID- 27506026
TI - [Influence of Submerged Plants on Microbial Community Structure in Sediment of
Hongze Lake].
AB - Phospholipid fatty acids (PLFAs) method was applied to analyze the influence of
submerged plants on sediment microbial community structure, in order to
investigate the changes of sediment microbial community structure for different
kinds of the submerged plants in different growth periods. Particularly,
Potamogeton crispus L., Potamogeton pectinatus L and the mixed group were chosen
as the typical submerged plants in Hongze Lake for investigation in this paper.
The results indicated that the change of total PLFAs in different periods was
significant, on the contrary, the PLFA change for different groups in the same
period was insignificant. The values of G+ PLFA/G- PLFA in the submerged plant
group were also highly related to the different growth periods, which
demonstrated that the root function of the submerged plant had a severe impact on
the microbial community in sediment. Furthermore, some environmental factors,
such as Temperature, pH, TOC and DO, were correlated to characteristic
phospholipid of PLFAs in sediment, which means the environmental factors could
also affect the microbial community structure.
PMID- 27506027
TI - [Community Structure Characteristics of Diatom in Reservoirs Located in the South
of Jiangsu Province, China and Its Control Factors].
AB - In order to understand the community structure characteristics of Bacillariophyta
and its controlling factors in reservoirs located in the Southeast, China, in the
geographic background of hills landscape and humid climate, 18 reservoirs were
investigated in June, 2015, during the period with high risk of diatom bloom,
covering water quality, and the community structures of phytoplankton. The
correlations between Bacillariophyta and other planktons with nutrients, water
depth, storage capacity, etc. were analyzed. The results showed that, 10
reservoirs reached the light extent of diatom bloom ( density between 100 x 104
1,000 x 104 cells . L-1 reservoirs in this area were generally in mesotrophic or
eutrophic state with considerably high total nitrogen concentrations; total
phosphorus and trophic level index were both closely correlated with
Bacillariophyta biomass. Phormidium in Cyanophyta was the dominating generus
among phytoplankton in terms of density; with respect to biomass,
Bacillariophyta, Chlorophyta and Cyanophyta were the top three phylum, and
Bacillariophyta accounted for 46. 8% of the total phytoplankton biomass, becoming
the most important one resulting in abnormal propagation of algae; Synedra
(51.5%) and Cyclotella (21.4%) were the main dominating genera in
Bacillariophyta, together with Achnanthes and Melosira. Deep water was favored by
Bacillariophyta to dominate among different phyla. Larger ratio between catchment
and reservoir storage capacity, on the other hand, caused the increase of trophic
level and chlorophyll, and benefited the shift of dominating phytoplankton from
Bacillariophyta to Chlorophyta and Cyanophyta, by which, the risk of algae bloom
would be increased. It reveals that to alleviate the risk of algae bloom and
protect drinking water resources, catchment management is crucial for the studied
reservoirs. And the establishment of nutrient reduction strategies needs to
consider the features of each individual reservoir, i. e. water depth, ratio
between catchment and capacity.
PMID- 27506028
TI - [Contamination and Ecological Risk Assessment of Mercury in Hengshuihu Wetland,
Hebei Province].
AB - Investigation on the concentrations and the distribution characteristics of total
mercury in atmosphere, water surface and soil/ sediments of Hengshuihu wetland
was carried out based on a uniform set point sampling method. The geoaccumulation
index and potential ecological risk index methods were simultaneously used to
assess the mercury pollution in Hengshuihu wetland ecosystem. The results showed
that: the total mercury content in Hengshuihu wetland atmosphere ranged from 1.0
to 5.0 ng . m-3, with an average of (2.9 +/- 0.85) ng . m-3; the total mercury
content in water surface ranged from 0.010 to 0.57 ug . L-1, with the average
value of (0.081 +/- 0.053) ug . L-1; the total mercury content in soil/sediment
ranged from 0.001 0 to 0.058 mg . kg-1, with an average of (0.027 +/- 0.013) mg .
kg-1. The distribution features of total mercury in Hengshuihu wetland were as
follows: the total mercury concentration in surface water of the shore was
significantly higher than that in the center (P < 0.05), but the total mercury
concentration of sediments in the center of the lake was significantly higher
than that at the shore (P < 0.05); the total mercury in the soil of shore had a
consistent trend with that in the atmosphere; high concentrations of total
mercury pollution were accompanied by severe human activities. The
geoaccumulation index showed that mercury pollution in Hengshuihu wetland was at
clean level; potential ecological risk index showed mercury contamination had a
low ecological risk in Hengshuihu wetland.
PMID- 27506029
TI - [Spatial Distribution and Potential Ecological Risk Assessment of Heavy Metals in
Soils and Sediments in Shunde Waterway, Southern China].
AB - Environmental quality of soils and sediments around water source area can
influence the safety of potable water of rivers. In order to study the pollution
characteristics, the sources and ecological risks of heavy metals Zn, Cr, Pb, Cu,
Ni and Cd in water source area, surface soils around the waterway and sediments
in the estuary of main tributaries were collected in Shunde, and ecological risks
of heavy metals were assessed by two methods of potential ecological risk
assessment. The mean contents of Zn, Cr, Pb, Cu, Ni and Cd in the surface soils
were 186.80, 65.88, 54.56, 32.47, 22.65 and 0.86 mg . kg-1 respectively, and they
were higher than their soil background values except those of Cu and Ni. The mean
concentrations of Zn, Cr, Pb, Cu, Ni and Cd in the sediments were 312.11, 111.41,
97.87, 92.32, 29.89 and 1.72 mg . kg-1 respectively, and they were higher than
their soil background values except that of Ni. The results of principal
component analysis illustrated that the main source of Cr and Ni in soils was
soil parent materials, and Zn, Pb, Cu and Cd in soils mainly came from wastewater
discharge of local manufacturing industry. The six heavy metals in sediments
mainly originated from industry emissions around the Shunde waterway. The results
of potential ecological risk assessment integrating environmental bioavailability
of heavy metals showed that Zn, Cu, Pb and Ni had a slight potential ecological
risk. Cd had a slight potential ecological risk in surface soils, but a moderate
potential ecological risk in surfaces sediments. Because the potential ecological
risk assessment integrating environmental bioavailability of heavy metals took
the soil properties and heavy metal forms into account, its results of risks were
lower than those of Hakanson methods, and it could avoid overestimating the
potential risks of heavy metals.
PMID- 27506030
TI - [Pollution Characteristics and Ecological Risk of PBDEs in Water and Sediment
from an Electronic Waste Dismantling Area in Taizhou].
AB - An e-waste dismantling industrial park of Taizhou was selected as the sampling
center, within a radius of 16 km, and a total of 30 sampling sites were designed
in three circles as follows: C (3 km), S (5-10 km) and R (10-16 km). Pollution
characteristics and ecological risk of polybrominated diphenyl ethers (PBDEs) in
water and sediments were investigated. The concentrations of PBDEs in water
ranged from 9.4 to 57.2 ng . L-1, with a mean value of 25.9 ng . L-1; and 3.7 to
38,775 ng . g-1, with an average of 2 779 ng . g-1 in sediments. BDE-209 was the
predominant congener. The spatial distribution patterns of PBDE levels in water
and sediment were both in the following order: C > S > R. Furthermore, the
concentrations of PBDEs in sediments showed significant negative correlation
against the distance from the industrial park (P < 0.01). Compared with other
regions around the world, the PBDEs contamination was more serious in the area,
which indicated that e-waste dismantling activity was one of the significant
sources for PBDEs pollution. It was estimated that a total of 30. 7 t PBDEs
(including 28. 9 t BDE- 209) was discharged into surrounding environment as a
result of dismantling industrial activities in last 40 years. A preliminary
ecological risk assessment for PBDEs in water and sediments was conducted by
hazard quotient method. The results demonstrated that the Penta-BDEs in the
center of e-waste dismantling area ( a radius of 1.5 km) was at particularly high
risk level and could cause serious influence on the ecological safety and human
health.
PMID- 27506031
TI - [Major Ionic Features and Their Controlling Factors in the Upper-Middle Reaches
of Wujiang River].
AB - The Wujing River, the largest river in Guizhou Province, is one of the most
important water resources for social and economical development. Recently, with
the fast population proliferation and rapid economic growth, the drainage basin
is intensively interfered by anthropogenic activities. The hydrochemistry of
surface water was analyzed from the upper-middle reaches of Wujiang River for
investigating the hydrochemical characteristics and their main influencing
factors. The results showed that the major cations of the four rivers were Ca2+
and Mg2+, accounting for more than 70%, and the main anions were HCO3- and SO42-,
occupying more than 85%. The hydrochemical characteristics in the four rivers
were found to be of HCO3-Ca type, and mainly determined by the carbonate rock
dissolution, while only a small proportion of them were of HCO3 . SO4-Ca type,
reflecting the influence of SO42- from anthropogenic activities. Compared to
hydrochemical data in 1999, there was an obvious increase in cations and anions
concentrations, majorly in NO3-, SO2- ion concentrations, which were
significantly affected by human activities. The Na+, K+ , Cl- in the river mainly
came from atmospheric precipitation, and Ca2+, HCO3-, Mg2+, mainly came from
carbonate rocks dissolution, while NO3- and SO42- mainly came from human
activities. According to principal component analysis and correlation analysis,
hydrochemical composition of Liuchong River was affected by human activity, and
that in the upstream of Sancha River was controlled by atmospheric precipitation
and the dissolution of carbonate rocks, that to the downstream was enhanced by
human activities. The main ion of Maotiao River was controlled by atmospheric
precipitation and carbonate rocks dissolution, and also affected by human
activity. The Nanming River, the Qingshui river's tributary, was mainly affected
by human activity, while the middle and lower reaches of Qingshui River were
affected by both the atmospheric precipitation and human activity.
PMID- 27506032
TI - [Export of Total Organic Carbon (TOC) from Karst Watershed and Its Influencing
Factors: An Example from Xueyudong Underground River System, Chongqing].
AB - High time-resolution auto-monitoring techniques were used to obtain the data for
TOC and hydrogeochemistry of groundwater, and air temperature and precipitation
from August 2014 to September 2015 in Xueyu Cave karst watershed, Southwest
China, and then the principal component regression model was used to reveal the
variation of TOC in groundwater and its influencing factors. The results
indicated that there were significant variations of the TOC and hydrogeochemistry
of groundwater in seasonal timescale. The temperature and specific conductance
(SpC) of groundwater showed higher values in summer and lower values in winter;
while an opposite variation pattern for pH in groundwater was observed, and the
TOC and turbidity of groundwater showed higher values in winter and summer
seasons and lower values in spring and autumn seasons. Meanwhile, high time
resolution data revealed that the TOC of groundwater responded quickly to
rainfall events with different intensities. Generally, an increasing trend for
TOC in groundwater was observed during raining and a decreasing trend for TOC in
groundwater was shown after rainfall events, especially after storm events due to
the dilution effect of rainfall. The export and variations of the TOC in
groundwater were mainly controlled by the precipitation and discharge of
underground river in the study area, as revealed by the principal component
regression model. The TOC increased with the increase of the precipitation,
discharge and turbidity of groundwater, and declined with the increase of air
temperature and pH of groundwater.
PMID- 27506033
TI - [Seasonal Variations and Controlling Factors of the Element Contents in Drip
Waters Collected from the Baojinggong Cave in Guangdong Province].
AB - Geochemical dynamics of cave water were monitored to unveil its seasonal
variation and controlling factors from December 2011 to May 2013 in Baojinggong
cave, north of Guangdong Province. Concentrations of elements such as Ba, Sr, Ca
and Mg of three drips in the cave were analyzed. The results showed that: (1) All
these elements of three drips displayed significant seasonal variations, but the
trends of seasonal variation of different elements or different drips were not
the same, which reflected that each element in different drips might be
controlled by different effects; (2) The low element contents of Drip1 and Drip2
during the heavy rainfall month showed that heavy rainfall could dilute the
concentrations of elements; (3) Mg/Ca had a positive relationship with Sr/Ca
ratio in three drips, and was higher in dry season and lower in rainy season. It
implied that the two proxies might be mainly controlled by precipitation, karst
water source, leaching effect and prior calcite precipitation (PCP), and
reflected the climate change.
PMID- 27506034
TI - [Tracing the Fecal Contamination Sources Based on Bacteroides 16S rRNA PCR- DGGE
in Karst Groundwater: Taking Laolongdong Underground River System, Nanshan,
Chongqing as an Example].
AB - Microbial contamination in karst groundwater continually increases and tracing
the source researches has become a hot topic for international researchers. In
this study, Laolongdong underground river at Nanshan, Chongqing was chosen as an
example to adopt filter membrane methods to monitor the fecal microbial
contaminations including the total bacterial concentration (TB), the total E.
coli concentration (TE), the total fecal coliform (FC) and the total fecal
Streptocoocci (FS). Bacteriodes was used as an indicator and PCR-DGGE analysis
was used to trace fecal contamination sources in karst groundwater. The results
suggested that groundwater in this area was seriously polluted by microbes from
feces. The concentrations of microbial parameters exceeded limited levels greatly
and the total bacterial amounts ranged 10-2.9 x 107 CFU . mL-1, the
concentrations of E. coli were between 4.3-4.0 x 105 CFU . mL-1, the max
concentration of FC was 1.1 x 106 CFU . (100 mL)-1 and the max concentration of
FS was 1.1 x 105 CFU . (100 mL)-1. The FC/FS ratios were mostly over 2 which
suggested that the main fecal source in groundwater was human feces. In addition,
PCR-DGGE contrastive analysis of Bacteroides communities showed that the
similarities between groundwater samples and human feces were in range of 7. 1%
69. 1% , and the similarity of the groundwater sample from Laolongdong
underground river outlet was 69.1% . Bacteroides community similarities between
groundwater samples and swine feces were in range of 1.1%-53.4%, and the
similarity of Laolongdong underground river outlet was merely 1.5%. The
similarity data implied that groundwater contamination resulted mainly from human
feces, swine feces contamination composed part of animals' fecal contamination,
and other animals' feces participated too. Furthermore, sequencing results of PCR
DGGE products revealed that most Bacteroides in groundwater originated from human
intestinal tract and human feces.
PMID- 27506035
TI - [Sources and Variation Characteristics of Dissolved Lipid Biomarkers in a Typical
Karst Underground River].
AB - Water samples in Qingmuguan underground river were collected to determine the
concentration of dissolved lipids, and their sources, composition and migration
characteristics in underground river were studied. The results were obtained as
follows. (1) The average content of various dissolved lipids decreased with
increasing distance of migration in Qingmuguan underground river, and the most
distinctive was dissolved saturated straight chain fatty acids with its content
decreasing by about 81.71%, from the initial 5,704 ng . L-1 to 1,043 ng . L-1.
(2) N-alkane could indicate the sources of dissolved organic matter in
underground river, but saturated straight chain fatty acid and fatty alcohol had
the advantage in indicating algae, bacteria and other microorganisms. (3) With
the increasing migration distance of Qingmuguan underground river, the input type
of dissolved organic matter in underground river was different, which might be
resulted from the heterogeneity of karst surface. (4) In ternary plot of alkane
sources, aquatic plants constituted the major contribution of dissolved organic
matter in Qingmuguan underground river, followed by higher plant, algae/
bacteria. Unlike higher plants and algae/bacteria, the contribution from aquatic
plants decreased with increasing migration distance of underground river. (5) To
a certain extent, TAR (alkane) values could reflect the rainfall, and the values
of CPI, L/H in saturated straight chain fatty acids might indicate the
degradation activities of bacteria.
PMID- 27506036
TI - [Formation of Halogenated By-products in Co2+ Activated Peroxymonosulfate
Oxidation Process].
AB - Sulfate radicals (SO4.-) generated by Co2+ catalyzed activation of
peroxymonosulfate (PMS) are highly oxidative and can be applied to degrade
various organic pollutants. It was revealed in this research that bromide could
be transformed in this process to reactive bromine species which reacted with
phenol subsequently, leading to the formation of bromophenols and brominated by
products such as bromoform and dibromoacetic acid. The formation of the
brominated by-products first increased and then decreased. The maximum yields of
bromoform (10.3 umol . L-1) and dibromoacetic acid (14.6 umol . L-1) occurred at
approximately 8 h with initial phenol, PMS, Br-, Co2+, concentrations of 0.05,
1.0, 0.2, and 5 umol . L-1, respectively. Formation of the brominated by-products
decreased with increasing pH. With constant total halides, increasing Cl-/Br-
ratio decreased the total formation of halogenated by- products but generated
more chlorinated byproducts. The findings of this research can provide valuable
information in assessing the feasibility of SO4.- based oxidation technologies in
real practice.
PMID- 27506037
TI - [Aspartic Acid Generated in the Process of Chlorination Disinfection By-product
Dichloroacetonitrile].
AB - In this study, a method was developed for the determination of
dichloroacetonitrile (DCAN) in drinking water by liquid- liquid micro-extraction
and gas chromatography/mass spectrometry ( LLE-GC/MS), which used 1,2
dibromopropane as the internal standard and methyl tertiary butyl ether (MTBE) as
the extractant for high accuracy. The aspartic acid was used as the precursor of
the DCAN formation during chlorination and the influencing factors were
evaluated. The formation mechanism of DCAN was also discussed. The results showed
that the DCAN amount increased with the increase of pH value under the neutral
and acidic conditions, however, the amount of DCAN decreased with the increase of
pH value under the alkali condition. And the final amount of DCAN under the
alkali condition was much less than that under the neutral and acidic conditions.
It was also found that the DCAN amount increased with the increase of chlorine
addition, while the temperature in the range of 10-30 degrees C had little
influence on the DCAN formation. The formation process of the DCAN from aspartic
acid by chlorination included seven steps, such as substitution, decarboxylation,
oxidation, etc and ultimately formed DCAN.
PMID- 27506038
TI - [Influencing Factors of Assimilable Organic Carbon (AOC) Formation in Drinking
Water During Ozonation Process].
AB - The influences of ozone dosage, pH and ionic strength on the formation of
Assimilable Organic Carbon (AOC) during ozonation were investigated. The result
demonstrated that within the range of 1-5 mg . L-1 O3, the formation of AOC
increased with increasing ozone dosage, but higher ozone dosage (9 mg . L-1)
resulted in reduction of AOC formation. AOC formation increased with higher pH
but decreased with increasing ionic strength. The result also showed that AOC
formation with hydrophobic fraction (HPO) was the most, followed by transphilic
fraction (TPI), and charged hydrophilic fraction (CHPI), while neutral
hydrophilic fraction (NHPI) was the least. It was found that AOC formation
related closely with SUVA of small molecular weight organics, and the lower SUVA
produced more AOC.
PMID- 27506039
TI - [Wastewater Quantity and Quality Fluctuation Characteristics of Typical Area of
Hybrid Sewage System].
AB - The inflow and infiltration problems cause large fluctuation in wastewater
quantity and quality in hybrid sewage system. This seriously challenges the
operation and management of sewage system. A multi-point on-line simultaneous
monitoring system was established in a typical hybrid sewage system. The key
characteristic parameters and their variation features under different
circumstances were studied. The result indicated that the daily variation rule
was obvious and appeared synchronous among multiple points at normal water level
under dry weather flow, but there was no synchronization in conductivity
variation among multiple points at high water level under dry weather flow. The
statistical distribution range of water level and conductivity was significantly
impacted by the seasonal rainfall change under dry weather. The statistical
distribution ranges of water level variation rate and conductivity variation rate
in specific time were significantly impacted by the rainfall. The response
features of water level and conductivity to rainfall intensity and pattern were
significantly different under different circumstances. The response sensitivity
of conductivity was higher than water level at normal water level and lower at
high water level. The database which could support the optimization of operation
and management in the hybrid sewage system was proposed based on the distribution
law of wastewater quality and quantity fluctuation under dry and wet weather, as
well as the variation rate features of wastewater quality and quantity during
rainfall obtained using the multi-point on-line simultaneous monitoring system.
PMID- 27506040
TI - [Preparation of HDTMA-modified Zeolite and Its Performance in Nitro-phenol
Adsorption from Wastewaters].
AB - In this study, natural zeolite was modified by HDTMA. Effects of the modified
conditions, HDTMA-modified zeolite doses, solution pH values, and reaction time
on nitro-phenol removal were investigated, and the adsorption kinetics and
isotherms were discussed. Compared with natural zeolite, HDTMA-modified zeolite
showed better performance in nitro-phenol removal. An adsorption capacity of 2.53
mg . g-1 was achieved when the concentration of HDTMA solution (pH = 10) was 1.2%
in preparation of modified zeolite. This adsorption capacity was higher than that
obtained by natural zeolite (0.54 mg . g-1). In adsorption tests, when HDTMA-
modified zeolite dose was adjusted to 8 g . L-1, the removal efficiency of nitro
phenol reached 93.9% after 90 min reaction, with wastewater pH of 6. Furthermore,
the nitro-phenol adsorption process could be well fitted to the pseudo-first
order kinetics model (R2 > 0.90), whereas the adsorption isotherm results
indicated that Langmuir model provided the best fitting for the equilibrium data
at different temperatures, with R2 of higher than 0.90.
PMID- 27506041
TI - [Selection of Suitable Microalgal Species for Sorption of Uranium in Radioactive
Wastewater Treatment].
AB - The amount of radioactive wastewater discharge was increasing year by year, with
the quick development of nuclear industry. Therefore, the proper treatment and
disposal of radioactive wastewater are essentially important for environmental
safety and human health. Microalgal biosorption of nuclide has drawn much
attention in the area of radioactive wastewater treatment recently, and the
selection of a proper microalgal species for uranium biosorption is the basis for
the research and application of this technology. The selection principle was set
up from the view of practical application, and 11 species of microalgae were
prepared for the selection work. Scenedesmus sp. LX1 has the highest biosorption
capacity of 40.7 mg . g-1 for uranium; and its biomass production in mBG11 medium
(simulating the nitrogen and phosphorus limits in the first-class A discharge
standard of pollutants for municipal wastewater treatment plant) was 0.32 g . L
1, which was relatively high among the 11 microalgal species; when grown into
stable phase it also showed a good precipitation capability with the
precipitation ratio of 45.3%. Above all, in our selection range of the 11
microalgal species, Scenedesmus sp. LX1 could be considered as the suitable
species for uranium biosorption in radioactive wastewater treatment.
PMID- 27506042
TI - [Magnetic Fe3O4Microparticles Conditioning-Pressure Electro-osmotic Dewatering
(MPEOD) of Sewage Sludge].
AB - For magnetic Fe3O4 microparticles conditioning--pressure electro-osmotic
dewatering (MPEOD) process of activated sludge (AS), the effects of operating
parameters (optimal dosage of Fe3O4, electric field duration, mechanical pressure
and voltage) on the dewatering efficiency and energy consumption were
investigated, and the optimal conditions were determined. Moreover, the
properties of supernatant and sludge along MPEOD process were studied as well as
the interaction force between the sludge biosolids. Taking the energy consumption
into consideration, the results showed that the optimal dewatering effect for AS
could be achieved with a magnetic Fe3O4 microparticles dosage of 0.15 g . g-1, an
electric field duration of 2 h, a mechanical pressure of 400-600 kPa and a
voltage of 30-50 V. When MPEOD was conducted at 400 kPa and 50 V for 2 h, the
sludge reduction rate reached 98.30%, the percentage of water removal was 99.34%
and the moisture content of AS decreased from 99.18% to 44.46%. The corresponding
consumption of energy was 0.013 3 kW . h . kg-1. The coagulation mechanism played
a slight role in the AS conditioning with magnetic Fe3O4 micro-particles. In
fact, magnetic Fe3O4micro-particles could greatly decrease the acid-base
interaction (WA) between AS biosolids, cause floc growth and enlarge pores in AS
aggregates, which will be beneficial to AS dewatering. Compared to DLVO theory,
the extended DLVO theory could accurately describe the aggregation and dispersion
behavior of sludge particles.
PMID- 27506043
TI - [Stability of Short-cut Nitrification Nitrogen Removal in Digested Piggery
Wastewater with an Intermittently Aerated Sequencing Batch Reactor].
AB - Stability of short-cut nitrification nitrogen removal performance was studied in
a step-feeding, intermittently aerated sequencing batch reactor (IASBR) at 30
degrees C to treat digested piggery wastewater. Results showed that the nitrogen
removal was greatly influenced by the ratio of chemical oxygen demand (COD) to
total nitrogen (TN) in the influent. Nitrite nitrogen kept accumulating up to 800
mg . L-1 when the influent COD/TN ratio was 0.8 +/- 0.2, and the removal rates of
TN, ammonium nitrogen and total organic carbon (TOC) were only 18.3% +/- 12.2%,
84.2% +/- 10.3% and 60.7% +/- 10.7%, respectively. By contrast, as the influent
COD/ TN ratio was increased to 2.4 +/- 0.5, the accumulated concentration of
nitrite nitrogen sharply decreased from 800 mg . L-1 to below 10 mg-L-1, and the
removal rates of TN, ammonium nitrogen and TOC were increased to over 90%, 95%
and 85%, respectively. Gradually shortened hydraulic retention time ( HRT)
reveales that the ammonia load is a restricting factor for nitrogen removal. The
ammonia load should be controlled at no more than 0.30 kg . (m3 . d) -1, or else,
the removal rates of TN, ammonium and TOC would be greatly decreased. The nitrite
accumulation rate over the whole run was 74.6%-97.8% and the TN removal rate in
the stable phase was over 90%. With efficient and stable short-cut nitrification
denitrification in a low COD/TN, moreover, and unnecessary for addition of
alkaline, IASBR shows great advantage for treating wastewater with high
concentration of ammonia while low COD/TN ratio.
PMID- 27506044
TI - [Effect of Irrigation Patterns on Soil CO2 and N2O Emissions from Winter Wheat
Field in North China Plain].
AB - The water-saving irrigation is the trend of modernized agriculture. This paper
aimed to study the effect of water-saving irrigation on soil CO2 and N2O
emissions. The field experiments were conducted under micro sprinkler irrigation
of integrated water and fertilizer (MSI) and conventional flooding irrigation
(FI) in winter wheat growth season in the west of North China Plain during 2013-
2014 using the static chamber method. This paper analyzed the seasonal variation
of soil CO2and N2O emissions under MSI and FI, and then compared the soil CO2 and
N2O emissions from treatments located in different vertical distance away from
micro sprinkler pipe. Root exclusion was used to estimate the components of soil
respiration and agricultural carbon sequestration intensity under MSI and FI in
winter wheat field. The results indicated that: (1) The average soil CO2
emissions under MSI and FI were 418.19 mg (m2 . h)-1 and 372.14 mg . (m2 . h)-1
respectively with no significant difference, and cumulative CO2 emissions under
MSI and FI were 2 150.6 g . m-2 and 1 904.6 g . m-2, respectively. (2) During
returning green stage to harvest stage of winter wheat, the highest soil CO2
cumulative emissions were found at the closest site to the micro sprinkler
irrigated pipes under MSI. However, there were no significant differences among
spatial treatments. (3) Under MSI and FI, soil heterotrophic respiration (C) was
468.49 g . m-2 and 427.31 g . m-2, and the net primary productivity (3) was
1988.21 g . m-2 and 1770.54 g . m-2; the carbon sink (C) during winter wheat
growing season was 1 519.72 g . m-2 and 1 343.24 g . m-2, respectively. (4) The
average N2O emissions under MSI and FI were 50.77 ug . (m2 . h)-1 and 28.81 ug .
(m2 . h)-1 respectively with no significant difference. Cumulative N2O emission
under MSI and FI was 272.67 mg . m-2 and 154.08 mg . m-2, respectively. (5)
During returning green stage to harvest stage of winter wheat, the farther the
distance away from the micro sprinkler irrigated pipes, the smaller the soil N2O
emissions. Moreover, there were no significant differences among sptial treatment
under MSI. Therefore, despite of the increase of soil CO2and N2O emissions, the
intensity of carbon sink increased during the transformation from traditional
flood irrigation to micro sprinkler irrigation in winter wheat fields.
PMID- 27506045
TI - [Characteristics of Dissolved CH4 and N2O Concentrations of Weihe River in
Xinxiang Section in Spring].
AB - Distributions of CH4 and N2O concentrations in Weihe River in Xinxiang City were
monitored in spring of 2015, and their influencing factors were discussed. The
result showed that CH4 and N2O were super-saturated in surface water of Weihe
River. The variation ranges of two gases' saturations in the surface water of
Weihe River were 147.59-2667.85 (CH4) and 4.06-188.25 (N2O). In the urban area,
significant correlation existed between N2O and NH4+-N concentrations (P < 0.01),
but in the new district, dissolved N2O concentration showed sharp increase
because of the water input from the urban sewage plants, illustrating that the
controlling mechanism on N2O production varied as pollutant characteristics
changed. Stepwise regression analysis showed that CH4 concentrations could be
explained by NH4+-N concentrations and water temperature, and CH4 concentrations
in the surface water of Weihe River was significantly correlated with NH4+-N
concentrations (R2 = 0.70, P < 0.01), suggesting that NH4+-N was the key factor
in regulating the production and assumption of CH4oxidation in Weihe River in
spring. Besides, this study showed that when there was less NO3--N but more NH4+
N in river water, CH4and N2O concentrations would be positively correlated,
indicating that different nitrogen sources would impact the coupling mechanism of
CH4and N2O productions.
PMID- 27506046
TI - [Effect of Stimulated N Deposition on N2O Emission from a Stipa krylovii Steppe
in Inner Mongolia, China].
AB - With fast development of industry, agriculture and society, very high N
deposition occurs in China. N deposition has exceeded 3 g . (m2 . a)-1 in some
areas of temperate steppes, which is a significant part of the Eurasia grassland,
but may possibly be sensitive to N deposition. To study the effect of N
deposition on N cycling in typical temperate steppe, N2O emissions were measured
in a Stipa krylovii steppe in Inner Mongolia for a whole year. A field control
experiment of simulated N deposition (by NaNO3 addition) was also carried out at
6 dose levels, CK (control), N2 [2 g . (m2 . a)-1], N5 [5 g . (m2 . a)-1], N10
[10 g . (m2 . a)-1], N25 [25 g . (m2 . a)-1], and N50 [50 g . (m2 . a)-1]. The
results showed that the natural N2O-N emission flux was 0.10 g . (m2 . a)-1,
accounting for about 3% of the total N deposition, and much depended on soil
water content and soil temperature under ambient N deposition. In addition,
enhanced N deposition might significantly increase N2O emission, especially at
very high N doses (N25 and N50 treatments). The annual N2 0 emission flux showed
a linear relationship with the N addition. Greater attention should therefore be
paid to the relatively high N2O emission in the typical temperate steppe in
China.
PMID- 27506047
TI - [Response of Soil Respiration and Organic Carbon to Returning of Different
Agricultural Straws and Its Mechanism].
AB - Soybean, maize and rice straws were selected as raw materials to study the
response of the soil respiration (SR) and soil organic carbon (SOC) to returning
of different straws in the Chongming Dongtan area. The results showed that all of
SR, SOC and the plant biomass of the lands with returning of different straws
were higher than those of the controls. The soil with soybean straw returning
possessed the lowest SR and highest SOC among the three kinds of straws, meaning
its higher soil organic carbon sequestration capability than corn and maize
straws returning. Straw returning significantly enhanced soil dehydrogenase, beta
glycosidase activities and microbial biomass, and soil dehydrogenase activity was
significantly correlated with soil respiration. The dehydrogenase activity of the
soil with soybean straw returning was the lowest, thus, the lowest SR and highest
SOC. Soybean straw had the highest cellulose and lignin contents and the lowest N
content among the three kinds of straws, resulting in its lowest
biodegradability. Therefore, when soybean straw was returned to soil, it was
difficult to degrade completely by soil microorganisms, thus the lowest soil
microbial activity, eventually leading to the lowest SR and highest SOC.
PMID- 27506048
TI - [Spatial Variability and Distribution Pattern of Soil Organic Matter in a
Mollisol Watershed of China].
AB - Spatial variability of soil organic matter and its distribution pattern are the
hot issues of soil scientific research. Selecting Haigouhe watershed as the study
area, this paper mainly focused on the spatial variability, distribution pattern
and its impact factors of SOM in the surface soil by classical statistics, Geo
statistics and "3S" technology. The results showed that: compared with the other
black soil areas, the SOM content in Haigouhe watershed was a little lower, there
was a spatial autocorrelation, and a moderate variability. Random factors, such
as human activities, cultivation measures and so on, had little impact on the
spatial variation, while the structural factors had a dominant function, and
there was a remarkable spatial anisotropy of SOM. The SOM content reduced
gradually from east to west with the familiar changes of height, so the co
kriging interpolation, selecting elevation as the co-variate, was employed to
improve the accuracy. The spatial variability of SOM and its distribution pattern
in Haigouhe watershed were greatly affected by topography and land use but weakly
influenced by traffic, villages and other social factors. The surrounding
environment of the samples would increase the uncertainty of spatial variability
and interpolation of SOM and it cannot be ignored in future studies. In summary,
it was a significant scientific research to analyze the spatial variability,
distribution pattern of SOM and its main impact factors in a mollisol hilly
watershed of China.
PMID- 27506049
TI - [Effects of Tillage on Distribution of Heavy Metals and Organic Matter Within
Purple Paddy Soil Aggregates].
AB - A long-term experiment was utilized to study the effects of tillage methods on
the contents and distribution characteristics of organic matter and heavy metals
(Cu, Zn, Pb, Cd, Fe and Mn) in aggregates with different sizes (including 1-2,
0.25-1, 0.05-0.25 mm and < 0.05 mm) in a purple paddy soil under two tillage
methods including flooded paddy field (FPF) and paddy-upland rotation (PR). The
relationship between heavy metals and organic matter in soil aggregates was also
analyzed. The results showed that the aggregates of two tillage methods were
dominated by 0.05-0.25 mm and < 0.05 mm particle size, respectively. The contents
of organic matter in each aggregate decreased with the decrease of aggregate
sizes, however, compared to PR, FPF could significantly increase the contents of
organic matter in soils and aggregates. The tillage methods did not significantly
affect the contents of heavy metals in soils, but FPF could enhance the
accumulation and distribution of aggregate, organic matter and heavy metals in
aggregates with diameters of 1-2 mm and 0.25-1 mm. Correlation analysis found
that there was a negative correlation between the contents of heavy metals and
organic matter in soil aggregates, but a positive correlation between the amounts
of heavy metal and organic matter accumulated in soil aggregates. From the slope
of the correlation analysis equations, we could found that the sensitivities of
heavy metals to the changes of soil organic matters followed the order of Mn > Zn
> Pb > Cu > Fe > Cd under the same tillage. When it came to the same heavy metal,
it was more sensitive in PR than in FPF.
PMID- 27506050
TI - [Distribution Characteristics and Potential Ecological Hazards Assessment of Soil
Heavy Metals in Typical Soil Profiles in Southeast Suburb of Beijing].
AB - To investigate the distribution characteristics and the potential ecology risk of
different types of heavy metals, soil samples were collected from various
stratigraphic sections in the southeastern suburb of Beijing, where soil heavy
metal (Cu, Pb, Cr, As) contents were measured and analyzed using multivariate
statistical analysis and the potential ecological risk index method. The results
showed that the concentrations of the four heavy metals followed the order of Cr
> Cu > As > Pb with variable coefficients ranging from 59.60% to 159.33% at 3-6 m
stratum, which all displayed a high degree of variability. The concentrations of
Cu and Pb were positively correlated with soil organic matter (SOM), cation
exchange capacity (CEC), etc, with higher eigenvalues in Factor 1 and 2,
demonstrating the impact of organic colloid on the occurrence of heavy metals.
The risk level of the specific heavy metal followed the order of As > Cu > Pb >
Cr, where As already showed a medium potential ecological risk in the studied
area.
PMID- 27506051
TI - [Contamination Assessment and Sources Analysis of Soil Heavy Metals in Opencast
Mine of East Junggar Basin in Xinjiang].
AB - The opencast mine of East Junggar Basin in Xinjiang is the largest self-contained
coalfield in China, and the ecological environment of the opencast is very
fragile because of its arid climate and poor soil. In this study, 50 soil samples
(from 0 to 30 cm depth soil at intervals of 10 cm) in opencast Mine of East
Junggar Basin in Xinjiang were collected in order to explore the heavy metals
contamination of the coal mining. The contents of zinc (Zn), copper (Cu), cadmium
(Cr), lead (Pb), mercury (Hg) and arsenic (As) were measured and the degree of
pollution was assessed by Nemerow index, geo-accumulation (Igeo) index and
potential ecological risk index. In addition, the layered comparison, dust fall
and the distance between coal mine and samples location were used to analyze the
source of heavy metals contamination. The results showed that value of As
surpassed the Chinese soil quality standard class I (GB 15618-1995) mostly
severely, followed by Cr, a relatively lower surpass was obtained by Hg and Cu,
while Zn and Pb did not surpass the standard. According to the standard, the soil
heavy metals content of research region was in light pollution status and the
pollution index for each heavy metal followed the order of As (2.07) > Cr (0.95)
> Cu (0.55) > Zn (0.48) > Hg (0.45) > Pb (0.38), which demonstrated a heavy
pollution of As and clean status of others. Additionally, an Igeo value of 1.14
for Hg reflected a moderated pollution. The major contribution factor was Hg with
a risk index of 251.40. The source analysis showed that the content of Pb in the
surface soil (10-20 cm) was different from that in the deep layer (20-30 cm),
which may be caused by coal combustion and other human activities. The sources of
Hg and As were similar and may come from coal combustion. The distance to the
mining area was not the major factor affecting the diffusion of heavy metals,
other candidate factors included terrain, aspect and wind direction, etc.
PMID- 27506052
TI - [Effect of Nano-TiO2 on Release and Speciation Changes of Heavy Metals in Soil].
AB - The effects of nano-TiO2 on migration and transformation of heavy metals in soil
were investigated by outdoor flooding simulation experiments. Cr, Pb, Zn, Cd and
Cu contents of different forms were determined in soil of typical fluctuating
zone of Three Gorges Reservoir. The results showed that, after flooding months,
both addition of 4 g . kg-1 of rutile and anatase particles resulted in the
release of about 30% Cr into the water. Nano-TiO2 particles mainly promoted the
dissolution of oxidizable residual Cr, and elevated its ecological risk. Thus
nano-TiO2promoted the activation of chromium and improved the mobility of
chromium in soil. 4 g . kg-1 of rutile particles caused the decrease of acid
exchangeable lead by 25.92% and oxidizable lead by 33.09%, and enhanced the
mobility of Pb. However, anatase particles caused the increase of oxidizable zinc
by 30% in soil, which facilitated fixing of zinc. In addition, two types of nano
TiO2particles had no significant effect on the speciation changes of Cu and Cd.
Therefore, the effect of nano-TiO2 on release and transformation of Cr in soil
was the largest, followed by Pb and Zn. This needs special attention when using
nano-TiO2 to remediate heavy metals contaminated soil and assessing its
environmental risk.
PMID- 27506053
TI - [Reduction Kinetics of Cr (VI) in Chromium Contaminated Soil by Nanoscale
Zerovalent Iron-copper Bimetallic].
AB - Nanoscale zerovalent iron-copper bimetallic (nZVI/Cu) was produced by liquid
phase reduction and characterized by SEM and XRD. The remediation of Cr (VI)
contaminated soil was conducted with nZVI/Cu, and the affecting factors and
reduction kinetics were investigated. The results indicated that nZVI/Cu was
effective in the degradation of Cr(VI) in soil at an initial pH of 7 at
30'C.After 10 min of reaction, Cr(VI) in the soil was completely degraded when
the. concentration of nZVI/Cu was 2 g . L-' and the concentration of Cr(VI) in
contaminated soil was 88 mg . kg-1. nZVI/Cu amount, pH value, reaction
temperature, and the concentration of humic acid affected the degradation of
Cr(VI). The removal efficiency of Cr(VI)--increased with increasing reaction
temperature and decreased with increasing initial pH value. Humic acid had a
certain impact on the degradation of Cr(W) in soil. The removal of Cr (VI)
followed the pseudo first order reduction kinetics model, and the relationship
between the reduction rate and the reaction temperature accorded with Arrhenius
law, and the reaction activation energy (Ea) was 104.26 kJ . mol-1.
PMID- 27506054
TI - [Inhibition of Low Molecular Organic Acids on the Activity of Acidithiobacillus
Species and Its Effect on the Removal of Heavy Metals from Contaminated Soil].
AB - Application of organic fertilizer can reduce the solubility and bioavailability
of heavy metals in contaminated soil, but in the flooded anaerobic environment,
organic fertilizer will be decomposed to produce a large number of low molecular
organic acids, which can inhibit the biological activity of Acidithiobacillus
species. Batch cultures studies showed that the monocarboxylic organic acids
including formic acid, acetic acid, propionic acid, and butyric acid exhibited a
marked toxicity to Acidithiobacillus species, as indicated by that 90% of
inhibitory rate for Fe2 and So oxidation in 72 h were achieved at extremely low
concentrations of 41.2 mg . L-1, 78.3 mg . L-1, 43.2 mg . L-1, 123.4 mg . L-1 and
81.9 mg 230. 4 mg . L-1, 170.1 mg . L-1, 123.4 mg . L-1 respectively. Of these
organic acids, formic acid was the most toxic one as indicated by that Fe2 and So
oxidation was almost entirely inhibited at a low concentration. In addition, it
was found that Acidithiobacillus ferrooxidans was more sensitive to low molecular
organic acids than Acidithiobacillus thiooxidans. What's more, there was little
effect on biological acidification process of heavy metal contaminated soil when
organic acids were added at initial stage (Oh), but it was completely inhibited
when these acids were added after 12 h of conventional biological acidification,
thus decreasing the efficiency of heavy metals dissolution from soil.
PMID- 27506055
TI - [Contribution of Particle Size and Surface Coating of Silver Nanoparticles to Its
Toxicity in Marine Diatom Skeletonema costatum].
AB - Due to the unique antibacterial properties, silver nanoparticles (AgNPs) have
been widely used in commercial applications. In this study, the toxicity of three
kinds of AgNPs with different sizes and surface coatings to marine diatom
Skeletonema costatum (S. costatum) was studied, which was one of the dominant
species in estuarine and coastal areas. All three kinds of tested AgNPs inhibited
the growth of exposed S. costatum under acute exposure condition, and the order
of toxicity was 10 nm-OA > 10 nm-PVP > 20 nm-PVP. Given the condition of similar
particle size, oil amine surface coated AgNPs were more toxic than polyvinyl
pyrrolidone (PVP) surface coated AgNPs in S. costatum in term of cytotoxicity.
With the same surface coating, the toxicity of AgNPs in S. costatum was affected
by its hydrodynamic diameter and exposure concentrations. When the concentration
of AgNPs was less than 500 ug . L-1, larger sized AgNPs showed greater toxicity;
When the concentration was greater than or equal to 500 ug . L-1, smaller AgNPs
exhibited greater toxicity. At molecular level, 50 ug . L-1 10nm-PVP
significantly upregulated expression level of 3HfcpA (P < 0.05) and significantly
downregulated expression level of Dl (P < 0.05), and 500 ug . L-1 10nm-OA
significantly upregulated 3HfcpA expression (P < 0.05), while 20 nm-PVP treatment
group didn't show any significant change. Exposed diatom demonstrated sensitive
photosynthesis response to small size and PVP coated silver nanoparticles at
molecular level. This study suggested that the toxicity of AgNPs to marine
microalgae was largely controlled by the particle size, surface coating, exposure
medium, exposure concentration and other factors. The smaller the particle size,
the greater the toxicity of AgNPs, and the particle size of AgNPs played an
important role in the toxicity of AgNPs in marine diatom S. costatum.
PMID- 27506056
TI - [Rhizospheric Mechanisms of Hemerocallis middendorfii Trautv. et Mey. Remediating
Petroleum-contaminated Soil and Metabonomic Analyses of the Root Systems].
AB - The effects of a special ornamental plant Hemerocallis middendorfii Trautv. et
Mey. on remediating petroleum-contaminated soil from the Dagang Oilfield in
Tianjin, China, was studied by a greenhouse pot-culture experiment and the
gradients of TPHs were 0, 10,000 and 40,000 mg . kg-1. The results suggested that
H. middendorfii had a high tolerance to TPHs (<= 40,000 mg . kg-1). And H.
middendorfii significantly (P < 0.05) promoted the removal rate of TPHs (53.7%
and 33.4%) compared with corresponding controls (31.8% and 12.0%) by natural
degradation, respectively. The relative abundance of amino acids, organic acids
and sugars and others in soil were analyzed by gas chromatography-mass
spectrometry (GC-MS), and PCA and PLS-DA models were to investigate the
rhizospheric mechanisms. The results suggested that H. middendorfii changed the
distribution characteristics of each component in soil, and the glucopyranoside
played a key role in the removal of TPHs. Furthermore, the results about
comparative metabolic profile showed that some special metabolites were only
found in the contaminated groups, including alanine, tetradecanoic acid,
hexadecanoic acid and 9,12-octadecadienoic acid. Additionally, the exposure of
TPHs changed the primary metabolic flux of roots, and caused the significant (P <
0.01) change of metabolites. In conclusion, H. middendorfii might be an enduring
ornamental plant for effective remediating TPHs (<= 40,000 mg . kg-1) in soil.
But the exposure of TPHs had changed the metabolic profile of H. middendorfii in
roots, which might be the metabolic response of H. middendorfii to petroleum
contaminated soil.
PMID- 27506057
TI - [Effects of Thermophilic Composting on Antibiotic Resistance Genes (ARGs) of
Swine Manure Source].
AB - To investigate the effects of thermophilic composting process on antibiotic
resistance genes (ARGs) of swine manure source at a field scale, the abundance of
four erythromycin resistance genes (ermA, ermB, ermC and ermF), three beta-lactam
resistance genes (blaTEM, blaCTX and blaSHV) and two quinolone resistance genes
(qnrA and qnrS) were quantified by quantitative PCR ( qPCR) during the composting
process. The results suggested that the erm genes' copy numbers were
significantly higher than those of the bla and qnr genes in the early stage of
composting (P < 0.01). The maximum abundance of erm genes was ermB (9.88 x 108
copies . g-1), following by ermF (9.4 x 108 copies . g-1). At the end of the
composting process, bla and qnr genes were at low levels, while erm genes were
still at high levels. Even through ermF was proliferated comparing with the
initial copies. These results indicated that thermophilic composting process
could not effectively remove all ARGs. For some ARGs, compost may be a good
bioreactor resulting in their proliferation. Application of composting products
on farmland may cause transference of ARGs.
PMID- 27506058
TI - [Interaction Between Sulfonamide Antibiotics Fates and Chicken Manure
Composting].
AB - Based on aerobic manure composting with or without the addition of a mixture of
sulfadimethoxine SM2 and sulfamonomethoxine SMM (1:1, m/m), changes in the physic
chemical properties of manure compost, the microbial community physiological
profiles, the antibiotics concentration and the abundances of five antibiotic
resistance genes (ARGs) during the composting were tracked. The results indicated
that the introduction of sulfonamide antibiotics led to inhibition on the basal
respiration of manure compost during the early composting period, delayed the
formation of thermophilic temperature and reduced the conversion of nutrients
such as organic matter, ammonia nitrogen and nitrate nitrogen. Meanwhile, the
introduction of sulfonamide antibiotics dramatically affected the physiological
profile of microbial community in manure in the middle stage of composting. HPLC
MS/MS results showed that both SMM and SM2 in manure were completely degraded
within 14 days, while the degradation rate of SMM was faster than that of SM2.
For both composting treatments with or without addition of exogenous antibiotics,
the relative abundance of sull and sul2 showed an initial decline in the first 14
or 21 days and a slight increase thereafter. The addition of exogenous
antibiotics showed insignificant enhancement on increasing the relative abundance
of sul1 and IntI1 in manure, but resulted in an apparent increase in sul2
relative abundance. Although the fates of tetQ and tetW during composting were
different from that of sulfonamide ARGs, the introduction of sulfonamide
antibiotics into manure increased the relative abundance of tetracycline ARGs.
Redundancy analysis indicated that composting temperature correlated negatively
with sul1, sul2 and IntI1 relative abundance in manure but had no obvious
relationship with tetQ and tetW relative abundance. All the ARGs detected in this
work correlated negatively with C/N ratio and the nitrate nitrogen concentration
of manure compost but positively correlated with pH, moisture and ammonia
nitrogen concentration of manure compost.
PMID- 27506059
TI - Are You a Victim of Identity Theft?
PMID- 27506060
TI - Example of Coordinated Effort between Behavioral Health and Primary Health Care.
PMID- 27506061
TI - Osteogenesis Imperfecta.
PMID- 27506062
TI - Be Prepared: Phase 2 HIPAA Audits Set to Begin.
PMID- 27506063
TI - [Not Available].
PMID- 27506064
TI - [Migraine: from generic recommendations to practical taking in charge].
AB - Although with an 11% prevalence migraine is a major public health problem, many
patients are not satisfied with its handling by medical professionals. Migraine
is a clinical diagnosis based on typically lateralized throbbing headache with
nausea and/or photo- and phonophobia. It can in some be preceded by an aura with
transient focal neurological symptoms. There are several "red flags" of clinical
presentation, however, that should induce further examination with brain imaging
studies. Treatment is based on identifying and avoiding provoking factors, on
treating attacks with rescue medication (simple pain killers or triptans), on
identifying conditions for a prophylactic treatment by one of several possible
substance classes, and most importantly, on establishing a solid therapeutic
relationship with the patient.
PMID- 27506065
TI - [The dark side of facet joint].
AB - Low back pain (LBP) is a major medical and economical problem, because of its
high incidence. Indeed, 70-85% of adult people will suffer from this kind of pain
once in their life. We will focus in this article on chronic LBP, which represent
an annual prevalence of 30% and more specifically on mechanical pain, with our
without radiation into the legs. In case of failure of traditional analgesia
combining drugs and physical therapies, we can propose interventional pain
relief. This involves a series of diagnostic blocks (medial branch blocks),
followed by the treatment (radiofrequency ablation). This treatment remains
purely symptomatic. A multidisciplinary approach with patient's physical
reconditioning is therefore very important.
PMID- 27506066
TI - [Chronic postoperative pain].
AB - Chronic postoperative pain remains a frequent pathology whose global impact
approximates 20 and 30% and accounts for 20% of the consultations in a pain
center. Risk factors consider firstly each patient's feature and comorbidity and
also different surgical procedures with their technical approach. Neuropathic
pain compared to nociceptive pain is a great component in the postoperative
period and needs to be recognized by specific tests (DN4). Pain prevention
involves risk factors' detection, appropriate anesthetic support and effective
postoperative pain management. Treatment is based on the type of pain and
includes a multimodal analgesia with interventional pain therapy.
PMID- 27506067
TI - [It is not only about cost ... when it comes to generic medication].
AB - The aim of this qualitative study was to explore patients' representations
regarding generics in patients suffering from non-specific disabling chronic
musculoskeletal pain, as these patients are confronted with the issue of the
prescription and/or substitution of original formulations with generics.
Patients' representations suggest that they might be confident in taking a
generic medication: when the generic medication is prescribed by the physician
and each prescription is discussed, i.e., the patient is prescribed the generic
version of a given medication and not a generic medication. Economic arguments
are not sufficient to accept substitution. Negative representations require
attention and need be considered.
PMID- 27506068
TI - [Spinal cord stimulation for the management of chronic pain].
AB - Neuromodulation techniques modify the activity of the central or peripheral
nervous system. Spinal cord stimulation is a reversible and minimally invasive
treatment whose efficacy and cost effectiveness are recognized for the treatment
of chronic neuropathic pain or ischemic pain. Spinal cord stimulation is not the
option of last resort and should be considered among other options before
prescribing long-term opioids or considering reoperation. The selection and
regular follow-up of patients are crucial to the success of the therapy.
PMID- 27506069
TI - [Psychosomatic posttraumatic resonances in refugees].
AB - The recent flow of refugees in our countries connects the clinician to new
challenges: posttraumatic consequences, exile pathologies, cultural differences.
Moreover, the psychic pains express themselves often through the body in more or
less qualified ways, making a clear understanding of them difficult. From the
therapist's side, the confrontation to war violences and cultural differences
might create difficulties in establishing an empathic and fruitful therapeutic
alliance.
PMID- 27506070
TI - [Abiotrophia defectiva: an unusual cause of endocarditis].
AB - This article reports one of the rare cases of Abiotrophia defectiva endocarditis
with no underlying valvular condition. A sixty-three years old man was
hospitalized because of complicated respiratory sepsis with acute heart failure.
Hemocultures and echocardiogram enabled the diagnosis of A. defectiva
endocarditis. The clinical course was favorable under combined aminoglycoside and
cephalosporin. The patient ultimately required valvular replacement. A. defectiva
is a micro-organism part of the Nutritionnaly Variant Streptococci (NVS)
associated with a high mortality rate and often resistant to antibiotics.
Although A. defectiva is a rare cause of endocarditis, prompt recognition and
appropriate antibiotic treatment are essential to clinical course.
PMID- 27506071
TI - [Not Available].
PMID- 27506072
TI - [Not Available].
PMID- 27506073
TI - [Not Available].
PMID- 27506074
TI - [Not Available].
PMID- 27506075
TI - [Not Available].
PMID- 27506076
TI - [Not Available].
PMID- 27506077
TI - [Not Available].
PMID- 27506078
TI - [Not Available].
PMID- 27506079
TI - [Not Available].
PMID- 27506080
TI - [Not Available].
PMID- 27506081
TI - [Biological review of completed suicide].
AB - Family, twin and adoption studies have revealed genetic factors involved in
suicide, while the accumulation of stress and mental illnesses are major
contributing factors of suicide. Since higher lethality of suicidal behavior is
considered to increase familial liability to suicidal behavior, we believe
biological research of completed suicide is most important for a better
understanding of the pathophysiology in suicide. Dysregulated hypothalamic
pituitary-adrenal axis has gained a special interest in the neurobiology of
suicide, mostly because of the findings using a dexamethasone suppression test
(DST), in which DST non-suppressors show a nearly 10-fold higher risk of
completed suicide than DST suppressors in a depressed cohort. Other data mainly
from postmortem brain studies indicate abnormalities of the noradrenergic-locus
coeruleus system, serotonergic system, endogenous opioid system, brain-derived
neurotrophic factor, inflammatory cytokines and omega-3 fatty acid in completed
suicide. However, genetic research of complete suicide is behind other mental
problems because it is extremely difficult to obtain tissue samples of completed
suicide. Under the difficult situation, we now retain over 800 blood samples of
suicide completers thanks to bereaved families' cooperation. We are actively
working on the research of suicide, for instance, by performing a GWAS using 500
samples of suicide completers.
PMID- 27506082
TI - [Pharmacokinetics and safety of aripiprazole long-acting injection, following
multiple deltoid administrations in schizophrenia patients in Japan].
AB - Aripiprazole once-monthly (AOM) was previously approved for treatment of
schizophrenia as monthly injections in the gluteal muscle. The deltoid muscle
provides a more accessible injection site. The present study was conducted in
Japanese schizophrenia patients as a 24-week, open-label trial that assessed the
pharmacokinetics and safety of 5 sequential doses of AOM 400 mg (AOM 400) once
every 4 weeks administered in the deltoid muscle. Patients treated with an oral
atypical antipsychotic (other than aripiprazole) continued to receive their pre
study medication up to 14 days after the first AOM 400 injection. The completion
rate was 76.5% (n = 13/17). Mean aripiprazole plasma C(min) almost reached steady
state by the fourth AOM 400 injection. After the fifth AOM 400 injection, mean
aripiprazole AUC(28d), C(max) and C(min) were 165 MUg x h/ml, 331 ng/ml and 201
ng/ml, respectively, which were similar to previously published pharmacokinetic
parameters after the fifth gluteal injection of AOM 400. The most common
treatment-emergent adverse event (TEAE) was injection site pain (35.3%). Most
TEAEs were classified as mild in intensity. In conclusion, the deltoid injection
of AOM can be considered an alternative route of administration, as deltoid and
gluteal injections are interchangeable in terms of aripiprazole plasma
concentrations, with no additional safety issues.
PMID- 27506083
TI - [Newly developed nomenclature (Neuroscience-based Nomenclature)].
AB - The current nomenclature is based on clinical indications; for example, drugs
used for mania and psychosis are classified as "mood stabilizers" and
"antipsychotic drugs", respectively. This discrepancy between their names and
indications often confuses patients and their caregivers and sometimes leads to a
misunderstanding of the effects of prescribed medications. In addition, up-to
date scientific knowledge on these drugs has not been reflected in the current
nomenclature. To overcome these limitations of the current nomenclature,
following an initiative of the European Congress of Neuropsychopharmacology
(ECNP), a taskforce for psychotropic nomenclature was established with
representatives from 5 international organizations, including the Asian College
of Neuropsychopharmacology (AsCNP). The mission of this taskforce is to provide a
pharmacologically-driven (rather than indication-based) nomenclature, which is
now referred to as Neuroscience-based Nomenclature (NbN). The NbN project has
just started. Since it always takes time to change the culture, we understand the
transition will likely involve some expected and unexpected responses from the
field. However, we believe that such responses and feedback will surely improve
the quality of the NbN, which in turn will be beneficial for clinicians,
researchers, and patients as well as their caregivers.
PMID- 27506084
TI - Canine osteosarcoma cell lines contain stem-like cancer cells: biological and
pharmacological characterization.
AB - Cancer stem cells (CSCs) represent a small subpopulation of cells responsible for
tumor formation and progression, drug resistance, tumor recurrence and
metastasization. CSCs have been identified in many human tumors including
osteosarcoma (OSA). CSC distinctive properties are the expression of stem cell
markers, sustained growth, self-renewal and tumorigenicity. Here we report the
isolation of stem-like cells from two canine OSA cultures, characterized by self
renewal, evaluated by sphere formation ability, differential marker expression,
and in vitro proliferation when cultured in a medium containing EGF and bFGF.
Current therapies for OSA increased survival time, but prognosis remains poor,
due to the development of drug resistance and metastases. Chemotherapy shrinks
the tumor mass but CSCs remain unaffected, leading to tumor recurrence.
Metformin, a drug for type 2 diabetes, has been shown to possess antitumor
properties affecting CSC survival in different human and animal cancers. Here we
show that metformin has a significant antiproliferative effect on canine OSA stem
like cells, validating this in vitro model for further pre-clinical drug
evaluations. In conclusion, our results demonstrate the feasibility of obtaining
CSC-enriched cultures from primary canine OSA cells as a promising model for
biological and pharmacological studies of canine and human OSAs.
PMID- 27506085
TI - Application of next-generation sequencing to investigation of norovirus diversity
in shellfish collected from two coastal sites in Japan from 2013 to 2014.
AB - A better understanding of the role played by shellfish regarding the manner of
pathogen contamination, persistence, and selection may help considering
epidemiology of noroviruses. Thus, norovirus genotype profiles in shellfish
(Crassostrea gigas and Mitilus galloprovincialis) were investigated by using Next
generation sequencing (NGS) technology. In genogroup I (GI), 7 genotypes
(abbreviated as GI.2 to GI.7, and GI.9) were detected from C. gigas, whereas 9
genotypes (GI.1 to GI.9) were detected from M. galloprovincialis. The genotype
with the highest proportion found in both C. gigas and M. galloprovincialis was
GI.4, and the second highest was GI.3. In genogroup II (GII), 17 genotypes (GII.1
to GII.9, GII.11 to GII.17, GII.21 and GI.22) were detected from C. gigas,
whereas 16 genotypes (GII.1 to GII.8, GII.11 to GII.17, GII.21 and GI.22) were
detected from M. galloprovincialis. The genotype with the highest proportion in
both C. gigas and M. galloprovincialis was GII.4, the next highest differed
between C. gigas and M. galloprovincialis. To our knowledge, this study may be
the first trial to utilize the latest technology in this field, and reveal the
diversity of norovirus genotypes present in shellfish.
PMID- 27506086
TI - Elevated cortisol content in dog hair with atopic dermatitis.
AB - Canine atopic dermatitis (CAD) is a chronic relapsing inflammatory skin disease
occurring in 10% of the canine population. Although most studies have focused on
the pathophysiological mechanism involved in CAD, the detrimental impact of CAD
on quality of life has received only little attention. Hair cortisol analysis is
becoming a valuable tool in monitoring chronic stress. To further validate this
approach in CAD, we compared the hair cortisol concentration of atopic dogs with
that of healthy conditioned dogs. The extent and severity of cutaneous lesions of
atopic dermatitis were assessed according to modified CADESI-03 scores. In
addition, skin barrier function was evaluated by measuring transepidermal water
loss (TEWL) and stratum corneum conductance. The correlation between CAD severity
and hair cortisol concentration was evaluated. The level of hair cortisol
evaluated by ELISA assay showed that the atopic dermatitis group had
significantly increased cortisol levels compared to that of the healthy control
group. A significant positive correlation was identified between hair cortisol
level and the CADESI score in CAD patients. The TEWL value of the cubital flexor
of the forelimb in the atopic group was significantly higher compared to the
healthy controls. These findings imply that the hair cortisol analysis can be an
effective and objective biomarker in assessment of long-term stress of CAD
patients.
PMID- 27506087
TI - Evaluation of a combination of alfaxalone with medetomidine and butorphanol for
inducing surgical anesthesia in laboratory mice.
AB - The anesthetic effects of alfaxalone were investigated in mice. Mice were
administered alfaxalone (100 mg/kg) alone or the combinations of 0.3 mg/kg of
medetomidine and 5 mg/kg of butorphanol with alfaxalone at doses of 20 mg/kg
(M/B/A20), 40 mg/kg (M/B/A40), 60 mg/kg (M/B/A60), or 80 mg/kg (M/B/A80). Control
mice received 0.3 mg/kg of medetomidine, 4 mg/kg of midazolam, and 5 mg/kg of
butorphanol (M/M/B). Each drug was administrated by intraperitoneal (IP) or
subcutaneous (SC) routes. M/M/B IP did not achieve surgical anesthesia but M/M/B
SC achieved surgical anesthesia within 10 min after administration and maintained
anesthesia for 45 min. The anesthetic scores were very low after IP or SC
administration of alfaxalone alone. M/B/A20 IP and SC did not achieve surgical
anesthesia. M/B/A40 IP did not achieve surgical anesthesia but M/B/A40 SC
achieved surgical anesthesia within 10 min after administration and maintained
anesthesia for 35 min. M/B/A60 SC achieved surgical anesthesia within 5 min after
administration and maintained anesthesia for 75 min. By contrast, M/B/A60 IP did
not achieve surgical anesthesia. M/B/A80 SC achieved surgical anesthesia within 5
min after administration and maintained anesthesia for 85 min. By contrast,
M/B/A80 IP did not achieve surgical anesthesia and one mouse died about 10 min
after drug administration. Administration of atipamezole rapidly reversed
anesthesia induced by M/B/A60 in mice. These results suggest that M/B/A60 SC, an
alfaxalone-based combination, is suitable for inducing surgical anesthesia in
laboratory mice.
PMID- 27506088
TI - Surgical stabilization of the atlanto-occipital overlap with atlanto-axial
instability in a dog.
AB - The atlanto-occipital (AO) overlap in combination with atlanto-axial (AA)
instability was found in a dog. We hypothesized that ventral fixation of the AA
junction can stabilize the atlas and prevent AO overlap by reviewing our past
cases with AA instability. A standard ventral fixation of the AA junction using
stainless k-wires and polymethyl methacrylate (PMMA) was performed. The dog fully
recovered, and no complication was noted. The results of the postoperative CT
imaging supported our hypothesis. The ventral fixation of the AA junction is a
feasible treatment option for similar cases, although craniocervical junction
abnormalities (CJA) including AA instability are varied, and careful
consideration is required for each case.
PMID- 27506089
TI - Complex malformations of the urogenital tract in a female dog: Gartner duct cyst,
ipsilateral renal agenesis, and ipsilateral hydrometra.
AB - A 10-month-old female toy poodle was referred to the University of Tokyo
Veterinary Medical Center with a urogenital anomaly found during sterilization.
An exploratory laparotomy revealed a cyst adhering to the cervix and a unilateral
renal agenesis. Histopathology and immunohistochemical analysis of the cyst was
consistent with remnants of the Wolffian duct or a Gartner duct cyst. This is a
rare case of a canine Gartner duct cyst with renal agenesis and uterine anomaly.
We discuss the similarity of this case to that of humans and introduce a
classification in the literature for these complex urogenital malformations for
further clinical research into the precise diagnosis and appropriate surgical
planning.
PMID- 27506090
TI - Evaluation of weekly bathing in allergic dogs with methicillin-resistant
Staphylococcal colonization.
AB - We evaluated the efficacy of weekly bathing in reducing methicillin-resistant
Staphylococcus (MRS) colonization in canine allergic dermatitis in a pilot
clinical trial. Six dogs with allergic dermatitis controlled by prescription
medications were treated with weekly bathing for 1 month. The Canine Atopic
Dermatitis Extent and Severity Index version 3 (CADESI-03) and pruritus scores
and frequency of mecA-positive Staphylococcus spp. isolated from three body sites
between weeks 0 and 4 were compared. There was no significant difference in
CADESI-03 scores with bathing, whereas the pruritus scores were significantly
reduced (p < 0.05). Furthermore, MRS frequency was decreased in four of the six
dogs (p < 0.05). In conclusion, weekly bathing should be considered for reducing
MRS colonization in canine allergic dermatitis.
PMID- 27506091
TI - Water intoxication in adult cattle.
AB - Water intoxication is a common disorder in calves and is usually characterized by
transient hemoglobinuria. In contrast, the condition is very rare in adult
cattle, with few reports on naturally occurring cases. In the present report,
four female Japanese Black cattle, aged 16-25 months, showed neurological signs
when they drank water following a water outage. Hemoglobinuria was not grossly
observed, while severe hyponatremia was revealed by laboratory tests. Autopsy
indicated cerebral edema with accumulation of serous fluid in expanded Virchow
Robin spaces. These results indicate the possibility of water intoxication
associated with cerebral edema due to severe dilutional hyponatremia in adult
cattle.
PMID- 27506092
TI - An unusual case of thoracic ectopia cordis in a Toggenburg Goat and its three
dimensional images constructed with X-ray computed tomography.
AB - A two-day-old female Toggenburg goat with thoracic ectopia cordis (EC) was
diagnosed via radiography and computed tomography. The goat was born with EC,
defects of the sternum and a supra-umbilical abdominal wall, but without the
presence of Cantrell's syndrome. Necropsy and histopathological findings
indicated the affected kid had malformation of the heart with an enlarged left
ventricle. The findings showed the heart (9 x 5 x 5 cm) stayed outside the
thorax, and was covered by a semitransparent membrane. This report is the first
to describe a case of thoracic EC in a goat whose sternum was not developed fully
and was not connected to the ribs. It is also the first paper to describe three
dimensional images of this condition constructed from computed tomography scans.
PMID- 27506093
TI - VALUE OF PROTECTIVE STOMA IN RECTAL CANCER SURGERY.
AB - INTRODUCTION: Anastomotic leakage is the most serious surgical complication in
rectal surgery. The aim of this study was to find out whether a protective stoma
was capable of lowering the rate of clinical anastomotic leakage and to evaluate
the rate of anastomotic leakages requiring resurgery. MATERIAL AND METHODS: A
retrospective study included a sample of 149 consecutive patients with rectal
cancer who had undergone elective rectal resection with primary anastomosis.
After total mesorectal excision, the anastomosis was created using either the
single stapling or double stapling anastomotic technique. Anastomotic integrity
was verified by transanal air insufflations with the pelvis filled with saline. A
protective covering colostomy was added in selected cases and according to the
surgeon's preference. RESULTS: A protective stoma was created in 31% of patients.
Clinical anastomotic leakage occurred in 6.7% of patients (10/149). Anastomotic
leakage occurred in 8.5% of the patients with a protective stoma (4/47) and in
5.9% of those without a protective stoma (6/102), which was not statistically
significant. Surgery lasted significantly longer when a stoma had to be created
than in case when it was not needed (p=0.024). The overall rate of resurgery due
to postoperative surgical complications was 5.3% and in three cases this happened
because of anastomotic leakage. All patients with a protective stoma and clinical
anastomotic leakage were treated conservatively, compared to 50% of patients
without a protective stoma who suffered anastomotic leakage and had to be
operated. CONCLUSION: A stoma cannot prevent but it can surely minimize surgical
complications related to anastomotic leakage and it does reduce the rate of
resurgery.
PMID- 27506094
TI - POSTOPERATIVE VISUAL RECOVERY FOLLOWING SURGICAL TREATMENT OF CRANIOPHARYGIOMAS.
AB - INTRODUCTION: Craniopharyngiomas are rare tumors which are typically focused in
the sellar and suprasellar region. Secondary to mass effect, these tumors
commonly mediate neurologic, endocrinologic or visual functions. The purpose of
this study was to investigate the pre and postoperative visual acuity in patients
with a craniopharyngioma in the area of the optic chiasm. MATERIAL AND METHODS:
This retrospective study included 42 patients with a craniopharyngioma
demonstrated by computerized tomography or magnetic resonance imaging. The visual
status was analyzed both before and after surgery (10 days, one month and six
months after surgery). RESULTS: Progressive loss of visual acuity was a typical
initial eye symptom. Postoperatively, improvement in visual acuity was seen in
47.2% of eyes. Normal vision was attained in the majority of eyes (from 27%
preoperatively to 40% six months after surgery). The percentage of eyes with
heavily reduced visual acuity decreased as well (from 38% preoperatively to 11%
six months after surgery). Visual acuity improved at least in one eye in 36.58%
of patients, and 28% of patients achieved normal visual acuity in both eyes, six
months after surgery. The improvement of 0.5 and better at least in one eye was
observed in 33% of patients. The majority of eyes showed immediate improvement
after surgical decompression, during first ten postoperative days. CONCLUSIONS:
The majority of patients with craniopharyngioma show a significant improvement of
visual function, particularly in the first ten postoperative days.
PMID- 27506095
TI - ANTIVIRAL TREATMENT OF HEPATITIS C IN SERBIAN PRISON SETTING: MEDICAL TREATMENT
OUTCOMES AND PATIENTS' ADHERENCE.
AB - INTRODUCTION: Seroprevlence of chronic hepatitis C viral infection in
correctional facilities ranges from 16% to 49%. However, there are only very
limited data available on the course of hepatitis C viral infection and outcomes
oftreatment with pegylated interferon plus ribavirin in correctional settings.
The aim ofthis study was to assess the feasibility and effectiveness of use of
pegylated interferon plus ribavirin treatment in the Serbian correctional
setting. MATERIAL AND METHODS: The study sample consisted of the patients with
hepatitis C hospitalized in the Special Hospital for Prisoners in Belgrade
(Serbia) during 2007-2013. Health authorities approved treatment for 32 patients
out of 76 treatment-naive patients referred to this institution. The patients
(N=32) received 180 mcg pegylated interferon alfa-2a once a week plus oral
ribavirin in dosage of 800 mg or 1000/1200 mg/day for 24 or 48-week treatment.
All patients who completed therapy were assessed at the end of an additional 24
week treatment-free period for a sustained virological response. RESULTS:
Sustained virological response was achieved in 53.8% of hepatitis C viral
infection genotype I patients and in 73.3% and 66.6% of patients with hepatitis C
viral infection genotype 3 and 4, respectively. One patient with mixed genotype
(1, 2) did not achieve sustained virological response. The overall safety profile
of the treatment regimen was very good. The incidence of influenza-like symptoms
and depression were low A serious adverse event was recorded only in 6.4% of
patients. CONCLUSION: The results showed that pegylated interferon alfa-2a plus
ribavirin given once a week was well tolerated among prisoners and the regimen
had the same adherence and effectiveness as in general population.
PMID- 27506096
TI - TICK-BORNE ENCEPHALITIS VIRUS INFECTION IN HUMANS.
AB - INTRODUCTION: Tick-borne meningoencephalitis virus is a flavivirus that causes
the most important vector-borne central nervous system infection in many
countries of Europe and Asia. There are three subtypes of tick-borne encephalitis
virus: European, Siberian and the Far-Eastern subtype. TRANSMISSION: In endemic
areas, the virus remains in transmissive cycles between Ixodes ticks and small
rodents. CLINICAL PICTURE: In most cases (70-98%) infection goes
asymptomatically. In about one-third of meningitis cases, meningoencephalitis or
meningomyelitis is developed. Postencephalytic syndrome may be the complication
of the infection, presenting with neurological symptoms. DIAGNOSIS: Etiologic
diagnosis of tick-borne meningoencephalitis is only made on basis of laboratory
analyses. Reverse transcription-polymerase chain reaction is used for determining
the presence of virus in the blood and cerebrospinal fluid. Antibodies in blood
and cerebrospinal fluid can be detected by serological tests. PREVENTION: The
most efficient way to control this potentially severe disease with possible
serious long-term consequences is vaccination. It should be recommended to
persons who live or travel to endemic areas. CONCLUSION: In Serbia, tick-borne
encephalitis virus infection belongs to the list of reportable diseases; however,
there are no reported cases because the diagnostics is not performed routinely.
We believe that the significance of this zoonosis must be examined in our country
and some of its parts because of preliminary positive serological findings found
out in Vojvodina as well as because of reported cases in neighboring countries
such as Hungary and Croatia and its worldwide distribution.
PMID- 27506097
TI - THE TIBIAL APERTURE SURFACE ANALYSIS IN ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION
PROCESS.
AB - INTRODUCTION: The tibial tunnel aperture in the anterior cruciate ligament
reconstruction is usually analyzed as an ellipse, generated as an intersection
between a tibial plateau and a tibial bone tunnel. The aim of this study is to
show that the tibial tunnel aperture, which utilizes 3D tibial surface bone
model, differs significantly from common computations which present the tibial
tunnel anterior cruciate ligament aperture surface as an ellipse. MATERIAL AND
METHODS: An interactive program system was developed for the tibial tunnel
aperture analysis which included the real tibia 3D surface bone model generated
from a series of computed tomography images of ten male patients, their mean age
being 25 years. In aperture calculation, the transverse drill angle of 10 degrees
was used, whereas sagittal drill angles of 40 degrees, 50 degrees and 60 degrees
were used with the drill-bit diameter set to 10 mm. The real 3D and 2D tibial
tunnel aperture surface projection was calculated and compared with an ellipse.
RESULTS: According to the calculations, generated 3D aperture surfaces were
different for every patient even though the same drill parameters were used. For
the sagittal drill angles of 40 degrees, 50 degrees and 60 degrees, the mean
difference between the projected 3D and 2D area on the tibial plateau was 19.6 +/
5.4%, 21.1 +/- 8.0% and 21.3 +/- 9.6%, respectively. The difference between the
projected 3D area on the tibial plateau and ellipse surface was 54.8 +/- 16.3%,
39.6 +/- 10.4% and 25.0 +/- 8.0% for sagittal drill angles of 40 degrees, 50
degrees and 60 degrees, respectively. CONCLUSION: The tibial tunnel aperture
surface area differs significantly from the ellipse surface area, which is
commonly used in the anterior cruciate ligament reconstruction analysis.
Inclusion of the 3D shape of the tibial attachment site in the preoperative
anterior cruciate ligament reconstruction planning process can lead to a more
precise individual anatomic anterior cruciate ligament reconstruction on the
tibial bone. Both tibial aperture area generated in 3D and its projection on a
tibial plateau are larger than the ellipse surface; therefore, individual
characteristics of each patient have to be taken into consideration.
PMID- 27506098
TI - VARIATIONS IN TIMING OF ELECTIVE ORCHIDOPEXY.
AB - INTRODUCTION: Undescended testis or cryptorchidism is detected in 3% of full-term
male newborns, and inup to 33% of preemies. As the testicular descent may
sometimes resolve spontaneously during first months of life, cryptorchidism is
found in 1% of boys one year old. According to Consensus of Nordic experts in.
pediatric urology regarding cryptorchidism the optimal period for surgery is 12
18 months of age. The goal of this study was to identify the age of patients with
congenital undescended testis at the time of surgery. MATERIAL AND METHODS: A
retrospective study included all the cases of cryptorchid patients who had
undergone orchidopexy in the period from 2007 to 2014. The patients'. age and the
place of residence were analyzed. RESULTS: A total of 637 patients (722
orchidopexies) underwent the elective operative treatment of undescended testis
during the observed period. The analysis revealed that only 144 (22.60%) of
cryptorchid infants were operated on within their first 18 months of life. In the
group of 359 patients from* the urban environment, 101 (28.13%) were operated
under the age of 18 months. Among the 278 patients from the rural enviornment, 43
(15.46%) were 18 months and younger at the time of surgery. CONCLUSION: The
timing of surgical treatment of undescended testis in the study period was far
from the recommended optimal time. It is evidently necessary to plan and provide
additional information for pediatricians and parents about the current view on
cryptorchidism and consequences of the late treatment.
PMID- 27506099
TI - SUSCEPTIBILITY OF RESPIRATORY ISOLATES OF STREPTOCOCCUS PNEUMONIAE ISOLATED FROM
CHILDREN HOSPITALIZED IN THE CLINICAL CENTER NIS.
AB - INTRODUCTION: Streptococcus pneumoniae is one of the most common causes of
respiratory infections. The aim was to study the susceptibility to antimicrobial
agents of respiratory isolates ofStreptococcus pneumoniae obtained from
hospitalized children. MATERIAL AND METHODS: A total of 190 respiratory
pneumococcal isolates obtained from children aged from 0 to 14 years were
isolated and identified by using standard microbiological methods. Susceptibility
to oxacillin, erythromycin, clindamycin, tetracycline, cotrimoxazole, ofloxacin
and rifampicin was tested by disc diffusion method. Minimal inhibitory
concentrations for amoxicillin and ceftriaxone were determined by means of E
test. The macrolide-resistant phenotype was detected by double disc diffusion
test. RESULTS: All tested isolates were susceptible to amoxicillin and
ceftriaxone. The minimal amoxicillin concentration inhibiting the growth of 50%
of isolates and of 90% of isolates was 0.50 microg/ml and 1.0 microg/ml,
respectively and the minimal ceftriaxone concentration inhibiting the growth of
50% of isolates and of 90% of isolates was 0.25 microg/ml and 0.50 microg/ml,
respectively. Susceptibility to erythromycin and clindamycin was observed in
21.6% and 29.47% of isolates, respectively. The resistence to macrolides-M
phenotype was detected in 10.07% of isolates and constitutive macrolide
lincosamide-streptogramin phenotype (constitutive MLS phenotype) was found in
89.93% of isolates. All tested isolates were susceptible to ofloxacin and
rifampicin. CONCLUSION: Amoxicillin could be the therapy of choice in pediatric
practice. The macrolides should not be recommended for the empirical therapy of
pneumococcal respiratory tract infection in our local area.
PMID- 27506100
TI - LOWER BACK PAIN--SILENT SYMPTOM OF CHRONIC INFRARENAL ABDOMINAL ANEURYSM RUPTURE.
AB - INTRODUCTION: The rupture of infrarenal abdominal aortic aneurysm is a surgical
emergency condition with a high rate of mortality before the patients arrive at
hospital. The signs and symptoms of abdominal aortic aneurysm rupture into the
retroperitoneal cavity are pulsatile mass, abdominal pain, hypotension and shock,
but sometimes silent symptoms also hide a dangerous and life threatening
condition, such as chronic aneurysm rupture of abdominal aorta into the
retroperitoneal cavity. CASE REPORT: We present a patient having had the lower
back pain for 4 months, which had been recognized and treated as lumbar
ischialgia but which was eventually diagnosed to be chronic infrarenal abdominal
aortic aneurysm rupture by computed tomography angiography. The surgical
intervention was successful and the patient was discharged from hospital after 6
days without any clinical complications. Preoperative imaging by computed
tomography angiography of ruptured abdominal aortic aneurysm is highly sensitive
for detection of several specific signs for rupture. This condition leads to
urgent vascular surgery.
PMID- 27506101
TI - TRANEXAMIC ACID IN SURGICAL TREATMENT OF SCOLIOSIS IN CHILDREN: A CASE REPORT.
AB - INTRODUCTION: Children who are subjected to surgical treatment for scoliosis
usually end up receiving a lot of blood transfusions since they tend to lose one
or more blood volumes during the surgery. Tranexamic acid is an antifibrinolytic
agent, increasingly used in children to reduce perioperative blood loss in
various settings, including corrective surgery of scoliosis. CASE REPORT: A 12
year-old girl, weighing 44 kg, was admitted to our hospital for scoliosis
correction. She had congenital scoliosis caused by congenital malformation of
vertebrae. The surgery was performed under balanced general anesthesia. Two
central and one peripheral line were cannulated in case massive transfusion would
be required. Invasive monitoring was used, as well as prevention of hypothermia.
Since massive blood loss was expected, bolus of tranexamic acid had been
administered prior to the surgery. Tranexamic acid was given continuously in an
intravenous infusion during the surgery. Blood loss was only 10 ml/kg, and since
the hemoglobin value was orderline (89 g/l) during the surgery, the patient
received 10 ml/kg of packed red blood cells. The child was hemodynamically stable
throughout the surgery. After the completion of surgery, which lasted for 5
hours, the patient was extubated in the operating room. Postoperatively, the
patient was transferred to the surgical ward. Hemoglobin values were stable and
there was no need for additional blood replacement. CONCLUSION: Extensive blood
loss is common in pediatric scoliosis correction surgery, transfusion being
unavoidable in the majority of cases. In our patient, tranexamic acid proved safe
and effective in reducing perioperative blood loss and transfusion requirement.
PMID- 27506102
TI - VALPROATE, BIPOLAR DISORDER AND POLYCYSTIC OVARIAN SYNDROME.
AB - INTRODUCTION: Polycystic ovarian syndrome is a syndrome of ovarian dysfunction
with the principal features of hyperandrogenism and polycystic ovary morphology.
A large number of studies conducted on this topic have suggested a possible role
of anticonvulsants, particularly valproate, in the pathogenesis or risk factors
associated with polycystic ovarian syndrome. Bipolar treatment guidelines from
Canada and the United States of America recommend valproate as the first line
strategy in the acute treatment of bipolar disorder. DISCUSSION: Most persons
with bipolar disorder require maintenance treatment. Long-term administration of
valproate in women with bipolar disorder or epilepsy is believed to result in the
increased risk of hyperandrogenism, menstrual abnormalities and polycystic
ovaries. Valproate may also increase the risk of infertility and other associated
symptoms of polycystic ovarian syndrome. Therefore, particular caution is
indicated in the use of valproate in women of reproductive age. CONCLUSION: The
treatment of the female patients with bipolar disorder presents various
challenges for the clinician. Every woman of reproductive age needs to know the
risk and benefits of her pharmacologic treatment options. Bipolar disorder should
be considered chronic disorder, whose development is largely affected by hormonal
changes and reproductive cycle in women. These issues should be researched more
thoroughly in order to opt for the most appropriate treatment in women with
bipolar disorder.
PMID- 27506103
TI - [THE EVOLUTION OF MARKERS OF PROSTATE CANCER].
AB - The implementation of biochemical laboratory tests in oncology practice increased
exponentially during last decades and continues to be in progress nowadays. The
application of modern molecular genetic technologies permits using diagnostic
systems with greater diagnostic sensitivity and specificity. The new tests are
actively implemented permitting to diagnose physical presence of tumor systemic
manifestations of malignant neoplasm (cachexia, pyrexia), paraneoplastic
syndromes and also to detect tumor markers. The oncomarker permits to
differentiate malignant from benign tumor on the basis of quantitative
differences in content of corresponding antigene-tumor marker in blood serum
independently of localization of tumor nidus. The prostate cancer is a medical
social problem of male population. On initial stages, this disease can take its
course asymptomatically or with symptomatic conditioned by such concomitant and
more prevalent pathologies as chronic prostatitis and prostate benign
hyperplasia. The early diagnostic ofprostate cancer permits implementing timely
radical treatment frequently contributing to total recovery of patients. The
article presents detailed description of evolutionary conception of markers using
in diagnostic, staging and prognostication of course of prostate cancer. The acid
phosphatase was applied for the first time in early diagnostic of staging of
prostate cancer in 1974. Nowadays, in century of "OMX"-technologies, in common
clinical practice detection of RNA in urine of patient is used for staging
diagnostic and prognostication of progression of process of tissue
neotransformation.
PMID- 27506104
TI - [THE MARKERS OF BONE TISSUE METABOLISM. THE REFERENCE VALUES FOR THE KHANTY-MANSI
AUTONOMOUS OKRUG-YUGRA].
AB - The article defines reference values of particular markers of metabolism of bone
tissue common to residents of the Khanty-Mansi Autonomous Okrug-Yugra. The enzyme
linked immunosorbent assay was applied to analyze blood serum of 86 patients (43
males, 43 females) detecting concentration of C-tailed telopeptide of collagen
type I, osteocalcin, calcitonin, parathyroid hormone and 1.25(OH)2 vitamin D. The
following reference values were derived. The C-tailed telopeptide (ng/ml): 0.111
(0.071-0.162) for females and 0.146 (0.066-0.255) for males. The osteocalcin
(ng/ml): 20.6 (12.9-33.0) for females and 27.6 (12.0-61.9) for males. Calcitonin
(pg/ml) - 2.55 (1.90-3.76); parathyroid hormone (pg/ml) - 39 (13-88); 1.25(OH)2
vitamin D (pg/ml) - 10.5 (3.9-46.4). It was also noted that decreasing of average
indicators of vitamin D level and increasing of level of parathyroid hormone
among residents of the Khanty-Mansi Autonomous Okrug-Yugra can cause increasing
of intensity of accumulation of minerals in bone tissue as compared with
residents of middle latitudes.
PMID- 27506105
TI - [THE DIFFERENTIAL DIAGNOSTIC POSSIBILITIES IN EVALUATION OF IRON-DEFICIENT
CONDITION UNDER ANEMIAS].
AB - The article presents data concerning differential diagnostic possibilities of
evaluation of genuine iron-deficient anemia and anemia of chronic diseases. The
variety of mechanisms of development of anemia of chronic diseases is
demonstrated, including effect of humoral inhibitors of erythropoiesis, disorder
of iron metabolism at the expense of its redistribution into cells of macrophage
system, suppression of erythropoiesis resulted in redistributed or functional
iron deficiency. The data is presented concerning significance in diagnostic of
anemia of chronic diseases of such factors as content of ferritin, dissolving
receptors of transferrin and role of hepcidin protein in pathogenesis of anemia
of chronic diseases. The analysis of scientific publications demonstrated that
hepcidin is a negative regulator of iron metabolism. Under iron-deficient anemia
its level in blood decreases that contribute to extensive absorption of iron in
gastrointestinal tract. On the contrary, under anemia of chronic diseases its
content drastically increases and results in blocking of iron transport
everywhere, including internal epithelium, macrophages, placenta and other types
of cells. The hyper-production of hepcidin during infection and inflammation is
responsible for anemia of chronic diseases. The perspectives of development of
pharmaceuticals decreasing level of hepcidin for treatment of anemia of chronic
diseases is demonstrated.
PMID- 27506106
TI - [THE METHODICAL APPROACHES TO DIAGNOSTIC OF NIGHT PAROXYSMAL HEMOGLOBINURIA].
AB - The article presents diagnostic of night paroxysmal hemoglobinuria. The night
paroxysmal hemoglobinuria is an orphan disease characterized by absence of GPI
anchor on blood cells as a result of mutation of PIG-A gene on the short arm of X
chromosome. The particular proteins bounded with GPI-anchor implement function of
defense from activation of components of complement and development of membrane
attacking complex. The erythrocytes exposed to destruction in bloodstream are
among the most impacted. Therefore, one of the main signs of night paroxysmal
hemoglobinuria is complement-depending intravascular hemolysis which indicators
for a long time played a key role in diagnostic of night paroxysmal
hemoglobinuria. The actual technique of diagnostic of night paroxysmal
hemoglobinuria is flow cytometry. The analysis of night paroxysmal hemoglobinuria
clone is recommended to patients with hemolysis of unclear genesis, thrombosis of
cerebral and abdominal veins, thrombocytopenia and macrocytosis and also patients
with AA, myelodysplastic syndrome, myelofibrosis. The international protocol
recommended by the International Society of Clinical Cytometry (2010) is
implemented to diagnose night paroxysmal hemoglobinuria. The original technique
of evaluation of reticulocytes was developed with purpose to detect night
paroxysmal hemoglobinuria clone. The high correlation was substantiated between
size of night paroxysmal hemoglobinuria clone measured among reticulocytes
according to proposed mode and night paroxysmal hemoglobinuria clone measured
among granulocytes and monocytes detected according international standardized
approach.
PMID- 27506107
TI - [THE PHYSICAL CHEMICAL, BIOLOGICAL BASICS OF CELLS ABSORPTION OF UNESTERIFIED
FATTY ACIDS; ALBUMIN, CAVEOLIN, CLATHRIN AND LIPID-BINDING PROTEINS OF CYTOPLASM
(THE LECTURE)].
AB - From aposition of phylogenetic theory of general pathology, obesity and metabolic
syndrome are pathology of fatty cells. However, the first is a pathology of
phylogenetically early visceral fatty cells of omentum. They supply with
substratum of energy realization of biologic function of trophology, homeostasis,
endoecology and adaptation. The visceral fatty cells of omentum have no receptors
to insulin and synthesize adaptively insulin and they are not characterized by
biologic reaction of proliferation. The obesity is a pathology of late in
phylogenesis subcutaneous adpocytes. They are insulin-dependent and supply with
substratum of energy realization of one biologic function of locomotion--movement
at the expense of constriction of cross-striated miocytes. The adipocytes in
terms of adaptation synthesize humoral mediator adponectin and actively implement
biologic function of proliferation. Under both aphysiologic conditions increases
passive by gradient of concentration, absorption by cells albumin-unbound free
fatty acids in unionized form in micellae's composition. The passive aphysiologic
absorption of free fatty acids by cells which under intracellular
compartmentalization don't oxidize mitochondria results in synthesis,
accumulation of triglycerides in cytoplasm of cells which don't implement it
physiologically. The aphysiologic absorption of free fatty acids by cells, their
etherification in triglyceride, in particular, in phylogenetically late beta
cells of islets and either late cardiomyocytes which fatty acids don't synthesize
de novo results in development of aphysiologic processes and disorder of
function. From position of biology, these cells in vivo are subjected to loss
similar to apoptosis. The formation of corpuscles of apoptosis compromise
biologic function of endoecology activating biologic reaction of inflammation.
PMID- 27506108
TI - [THE CYTOMETRIC TECHNIQUE OF BINDING OF EOSIN-5-MALEIMIDE IN DIAGNOSTIC OF
INHERENT SPHEROCYTOSIS].
AB - The laboratory diagnostic of inherent spherocytosis is based on detection of
spherocytes in peripheral blood, decreasing of index of sphericity, decreasing of
osmotic resistance of erythrocytes. The new test of diagnostic of hereditary
spherocytosis build on molecular defect was developed on the basis of binding
extracellular fragments of protein of band 3 with eosin-5-maleimide (EMA-test).
The study was carried out to implement comparative analysis of sensitivity and
specificity of techniques applied to diagnose inherent spherocytosis. The
sampling of 94 patients with various forms of anemias was analyzed All patients
were applied complex clinical laboratory examination including analysis of
osmotic resistance of erythrocytes, erythrocytometry and EMA-test as specific
techniques of diagnostic of inherent spherocytosis. In 51 out of 94 patients
(54%) decreasing of values of EMA-test was detected and in 47 patients diagnosis
of inherent spherocytosis was confirmed. The standard values of EMA-test were
established in 43 patients (46%) and 12 patients out of them with established
diagnosis of inherent spherocytosis. Therefore, sensitivity of EMA-test made up
to 79% and specificity - 80%. The most sensitive techniques of diagnostic remain
osmotic resistance of erythrocytes (91%) and index of sphericity (up to 96%). But
the highest specificity in this respect has EMA-test (80%). Nowadays, none of
implemented techniques of diagnostic of inherent spherocytosis can be applied as
a universal one. The implementation of complex examination is needed for proper
diagnostic of disease.
PMID- 27506109
TI - [THE DEVICE REGISTRATION OF IMMUNE CHROMATOGRAPHIC EXPRESS-TESTS].
AB - The development of sector of "fast-testing" i.e. test-systems permitting carrying
out analysis during home visit of doctor or at primary examination of patient
without any additional devices and reagents is predominant tendency in
international practice. The immunochromatography is an effective technical
solution in out-laboratory diagnostic, which nowadays is actively applied in
controlling hundreds of diagnostically significant markers of infectious
diseases, metabolic and functional disorders. However, common
immunochromatography is focused on qualitative visual evaluation of results of
study i.e. conclusion on presence or absence of coloration of particular zones of
test-band. Therefore, the technical solutions retaining such merits of
immunochromatography as expressness and technical simplicity and at the same time
providing objectivity of diagnostic and increasing its informativeness are
extremely in demand. The review considers main methodical solutions and
tendencies of their practical implementation targeted at device documentation,
processing and interpretation of results of immunochromatography analysis. The
optical systems of registration in visible area of spectrum dominating in
assortment of modern detectors are presented. The new solutions oriented on
working with fluorescent, magnetic and electroconductive markers are presented
too. The perspectives of further development of this direction are characterized
including application as detectors of domestic communication devices and
formation of cloud data bases for storage and processing of information
concerning results of examinations.
PMID- 27506110
TI - [THE STANDARD VALUES OF SUB-POPULATIONS OF T-HELPERS OF DIFFERENT LEVEL OF
DIFFERENTIATION IN PERIPHERAL BLOOD].
AB - The study was carried out to develop standard indicators of relative and absolute
content of main populations of T-helpers in peripheral blood of conditionally
healthy donors. The examination was implemented to sampling of 52 healthy
individuals (29 males and 23 females) aged 18-65 years (median is 30 years). The
multicolor cytofluorimetric analysis was applied using panel of following
antibodies: CD45RA-FITC, CD62L-PE, CCR4-PerCP/Cy5.5; CCR6-PE/Cy7, CXCR3-APC, CD3
APC-AF750, CD4-Pacific Blue and CXCR5-Brilliant Violet 510TM. The T-helpers 1
were distributed in populations of cells with phenotypes CXCR5-CXCR3+CCR6-CCR4-,
also containing Th9, and CXCR5-CXCR3+CCR6+CCR4- referred as Thl/Thl7. The Th2
were detected an the basis of availability of CCR4 at the absence of all other
chemokin receptors. The Thi7, besides Thl/Thi7 mentioned above, were detected in
composition of CXCR5-CXCR3-CCR6+CCR4- and CXCR5-CXCR3-CCR6+CCR4+. The last
population also contained Th22. The follicular Th which expressed at their
surface CXCR5, formed six cellular populations with following phenotypes:
CXCR5+CXCR3-CCR6-CCR4- (Tfh/Tfh2), CXCR5+CXCR3-CCR6-CCR4+ (Tfh2), CXCR5+CXCR3
CCR6+CCR4- (Tfh17), CXCR5+CXCR3-CCR6+CCR4+ (Tfh17), CXCR5+CXCR3+CCR6-CCR4- (Tfh1)
and CXCR5+CXCR3+CCR6+CCR4- (Tfh1/Tfh17). The relative and absolute content of T
helpers of mentioned phenotypes was established both within the framework of
total population CD3+CD4+ of lymphocytes and among "naive" T-helpers (CD45RA
CD62L+), T-helpers of central (CD45RA-CD62L+) and effector (CD45RA- CD62L-)
memory and also "terminal-differentiated" CD45RA-positive cells of effector
memory with phenotype CD45RA+CD62L-. The study results can be applied as standard
indicators under diagnostic of pathologic conditions of immune system.
PMID- 27506111
TI - [THE DEVELOPMENT OF IMMUNE ENZYME AND IMMUNE CHROMATOGRAPHIC MONOCLONAL TEST
SYSTEM FOR DETECTING TULAREMIA AGENT].
AB - The immune enzyme and immunochromatographic test-systems for detecting tularemia
agent were developed on the basis of selected set of monoclonal antibodies having
immunochemical activity to antigens Francisella tularensis. The evaluation of
sensitivity and specificity of developed test-systems demonstrated that samples
provided detection of strains of F. tularensis in concentration from 5.0 x 105
mkxcm-3 to 1.0 x 106 mkxcm-3 and gave no false positive results in analysis of
heterologous microorganisms in concentration of 1.0 x 108 mkxcm-3.
PMID- 27506112
TI - [FROM THEORY TO PRACTICE. THE ROLE OF QUALITY CONTROL OF ANALYTICAL STAGE OF
STUDIES IN INCREASING CLINICAL INFORMATIVENESS OF LABORATORY TESTS].
AB - Nowadays, improving accuracy and clinical informativeness of results of studies
is one of main directions of development of laboratory. The article presents
originally developed algorithm of evaluation of quality of immunochemical studies
in part related to analytical stage. The case of application in practice of the
results of such evaluation is presented.
PMID- 27506113
TI - The hubris hypothesis: The downside of comparative optimism displays.
AB - According to the hubris hypothesis, observers respond more unfavorably to
individuals who express their positive self-views comparatively than to those who
express their positive self-views non-comparatively, because observers infer that
the former hold a more disparaging view of others and particularly of observers.
Two experiments extended the hubris hypothesis in the domain of optimism.
Observers attributed less warmth (but not less competence) to, and showed less
interest in affiliating with, an individual displaying comparative optimism (the
belief that one's future will be better than others' future) than with an
individual displaying absolute optimism (the belief that one's future will be
good). Observers responded differently to individuals displaying comparative
versus absolute optimism, because they inferred that the former held a gloomier
view of the observers' future. Consistent with previous research, observers still
attributed more positive traits to a comparative or absolute optimist than to a
comparative or absolute pessimist.
PMID- 27506114
TI - Structural Covariance Networks and Their Association with Age, Features of
Cerebral Small-Vessel Disease, and Cognitive Functioning in Older Persons.
AB - Recently, cerebral structural covariance networks (SCNs) have been shown to
partially overlap with functional networks. However, although for some of these
SCNs a strong association with age is reported, less is known about the
association of individual SCNs with separate cognition domains and the potential
mediation effect in this of cerebral small vessel disease (SVD). In 219
participants (aged 75-96 years) with mild cognitive deficits, 8 SCNs were defined
based on structural covariance of gray matter intensity with independent
component analysis on 3DT1-weighted magnetic resonance imaging (MRI). Features of
SVD included volume of white matter hyperintensities (WMH), lacunar infarcts, and
microbleeds. Associations with SCNs were examined with multiple linear regression
analyses, adjusted for age and/or gender. In addition to higher age, which was
associated with decreased expression of subcortical, premotor, temporal, and
occipital-precuneus networks, the presence of SVD and especially higher WMH
volume was associated with a decreased expression in the occipital, cerebellar,
subcortical, and anterior cingulate network. The temporal network was associated
with memory (p = 0.005), whereas the cerebellar-occipital and occipital-precuneus
networks were associated with psychomotor speed (p = 0.002 and p < 0.001). Our
data show that a decreased expression of specific networks, including the
temporal and occipital lobe and cerebellum, was related to decreased cognitive
functioning, independently of age and SVD. This indicates the potential of SCNs
in substantiating cognitive functioning in older persons.
PMID- 27506115
TI - Buccal mucosal irritation studies of sublingual apomorphine film (APL-130277) in
Syrian golden hamsters.
AB - AIM: Determine the potential for cheek pouch buccal mucosa irritation in hamsters
following administration of apomorphine hydrochloride film (APL-130277). METHODS:
Three studies were conducted with Syrian golden hamsters. (First study, four
hamsters received APL-130277 three times a day [TID] for 7 days. Second study,
four hamsters received APL-130277 once a day [QD] for days 1-3, twice a day [BID]
for days 4-7 and TID for days 8-21. Third study, 32 hamsters received either a
placebo strip or APL-130277-dosed TID for 28 days). For all the studies, the
macroscopic appearance of the buccal cavities was evaluated throughout the study.
In the third study, all animals were necropsied on day 29, and macroscopic and
histopathological examinations were performed. RESULTS: In the first and second
studies, the buccal mucosa of the cheek pouch did not show any signs of
irritation. In the third study, administration of APL-130277-dosed TID for 28
consecutive days did not result in observable local irritation of the buccal
mucosa. CONCLUSION: In all the studies, APL-130277 produced no irritation of the
cheek pouch buccal mucosa.
PMID- 27506117
TI - Editorial overview: Cancer immunology: genomics & biomarkers: Cancer immunity
through the prism of genomics and proteomics.
PMID- 27506116
TI - Nuclear receptor corepressors Ncor1 and Ncor2 (Smrt) are required for retinoic
acid-dependent repression of Fgf8 during somitogenesis.
AB - Retinoic acid (RA) repression of Fgf8 is required for many different aspects of
organogenesis, however relatively little is known about how endogenous RA
controls gene repression as opposed to gene activation. Here, we show that
nuclear receptor corepressors NCOR1 and NCOR2 (SMRT) redundantly mediate the
ability of RA to repress Fgf8. Ncor1;Ncor2 double mutants generated by
CRISPR/Cas9 gene editing exhibited a small somite and distended heart phenotype
similar to that of RA-deficient Raldh2-/- embryos, associated with increased Fgf8
expression and FGF signaling in caudal progenitors and heart progenitors. Embryo
chromatin immunoprecipitation studies revealed that NCOR1/2 but not coactivators
are recruited to the Fgf8 RA response element (RARE) in an RA-dependent manner,
whereas coactivators but not NCOR1/2 are recruited RA-dependently to a RARE near
Rarb that is activated by RA. CRISPR/Cas9-mediated genomic deletion of the Fgf8
RARE in mouse embryos often resulted in a small somite defect with Fgf8
derepression caudally, but no defect was observed in heart development or heart
Fgf8 expression. This suggests the existence of another DNA element whose
function overlaps with the Fgf8 RARE to mediate Fgf8 repression by RA and
NCOR1/2. Our studies support a model in which NCOR1/2 mediates direct RA
dependent repression of Fgf8 in caudal progenitors in order to control
somitogenesis.
PMID- 27506118
TI - Did Amendments to the Ontario Highway Traffic Act in 2009-2010 Affect the
Proportion of Alcohol-Related Motor Vehicle Collisions Seen at a Level I Trauma
Centre over a 10-year Period?
AB - OBJECTIVES: To determine if changes to the Ontario Highway Traffic Act (OHTA) in
2009 and 2010 had an effect on the proportion of alcohol-related motor vehicle
collisions (MVCs) presenting to a trauma centre over a 10-year period. METHODS: A
retrospective review of the trauma registry at a Level I trauma centre in
southwestern Ontario was undertaken. The trauma registry is a database of all
trauma patients with an injury severity score (ISS) >=12 and/or who had trauma
team activation. Descriptive statistics were calculated. Interrupted time series
analyses with ARIMA modeling were performed on quarterly data from 2004-2013.
RESULTS: A total of 377 drivers with a detectable serum ethanol concentration
(SEC) were treated at our trauma centre over the 10-year period, representing 21%
of all MVCs. The majority (330; 88%) were male. The median age was 31 years,
median SEC was 35.3 mmol/L, and median ISS was 21. A total of 29 (7.7%) drinking
drivers died from their injuries after arriving to hospital. There was no change
in the proportion of drinking drivers after the 2009 amendment, but there was a
significant decline in the average SEC of drinking drivers after changes to the
law. There was no difference in the proportion of drinking drivers <=21 years
after introduction of the 2010 amendment for young and novice drivers.
CONCLUSIONS: There was a significance decline in the average SEC of all drinking
drivers after the 2009 OHTA amendment, suggesting that legislative amendments may
have an impact on drinking before driving behaviour.
PMID- 27506119
TI - Toxicity study of food-grade carboxymethyl cellulose synthesized from maize husk
in Swiss albino mice.
AB - Food-grade carboxymethyl cellulose was prepared from maize husk agro-waste and
was evaluated sub-chronic oral toxicity in Swiss albino mice. 40 male mice were
divided into 4 groups and fed diets with 0 (control) - 10% CMC for a period of 3
months. Daily oral doses were 5 - 20mg/g body weight to the mice/day. Animal care
and handling were conformed according to internationally accepted standard
guidelines. Haematological and biochemical parameters were monitored during this
period. At the end of the study, tissues and organs were studied for
histopathological changes. Repeat-dose oral toxicity study was carried out
according to OECD guideline 408. The result did not show any treatment related
abnormalities in terms of haematological and biochemical parameters. However,
water intake, urine production and urinary sodium excretion increased with
increasing doses of CMC. The weekly body weight showed no significant differences
between control and mice treated with different doses of CMC. In mice of the
treated groups, no abnormalities in the histopathology of liver, heart, lung and
kidney were detected. This indicated the prepared CMC has no toxic effect at
different doses on cellular structure, and support the safety use of CMC as food
additives and an excipient for pharmaceuticals.
PMID- 27506120
TI - Design and development of Albizia stipulata gum based controlled-release matrix
tablets in cancer therapeutics.
AB - The present study deals with the development of natural macromolecule gum Albizia
stipulata (AS) based novel pharmaceutical excipient for the controlled-release of
paracetamol (PC). Central composite design (CCD) two-factor, five-level was used
for the optimization of independent variables AS gum and compression force (CF)
based on desired response variable drug release (DR) of paracetamol matrix
tablets (PCMT). The optimized PCMT was prepared by wet granulation method and
screened for pre- and post- compression parameters, and were characterized. The
optimized PCMT (F14) formulation showed favorable in vitro release of PC (65%) in
12h, and the release kinetics followed zero order anomalous diffusion mechanism.
AS gum exerted significant (p<0.001) anticancer activity with 98.25% inhibition
at 2000MUg/mL (IC50=179.12MUg/mL) against A549 cell line. PC and PCMT showed
78.56% inhibition (IC50 value=856.58MUg/mL) and 93.68% inhibition (IC50
value=396.35MUg/mL) respectively, symbolizing that the gum remarkably potentiated
the anticancer effect of PC in formulation after 24h treatment by inducing
apoptosis. This is the first report on A. stipulata gum as a promising biopolymer
for drug delivery application in cancer therapeutics.
PMID- 27506121
TI - Radiation formation of functionalized polysaccharide-protein based skin mimicking
semi- inter penetrating network for biomedical application.
AB - Radiation treatment of chitosan, gelatin, polyvinyl alcohol (PVA) and
polyacrylamide [poly(AAm)] will form the sterile hydrogel wound dressings which
can mimic the artificial skin function in wound therapy. These polymers have been
characterized by cryo-scanning electron micrographs (cryo-SEMs), atomic force
microscopy (AFM), Fourier transform infrared spectroscopy (FTIR) and 13C solid
state nuclear magnetic resonance (NMR) spectroscopy and swelling studies. Some
important properties of hydrogel wound dressings like drug delivery, blood
compatibility, wound fluid absorption, antioxidant activity, oxygen permeability,
water vapour permeability, microbial penetration, mucoadhesion and mechanical
properties have also been determined. The release profile of moxifloxacin from
the polyacrylamide functionalized chitosan-gelatin matrix followed Fickian
diffusion mechanism and release profile best fitted in Korsmeyer-Peppas kinetic
model. The hydrogel films are permeable to O2 and H2O vapour and impermeable to
microbes in open environment and showed high wound absorption, good mucoadhesion
and antioxidant activity. Beside release of antibiotic, the inherent wound
healing potential of chitosan, adhesion capacity of gelatin, film forming ability
of PVA and wound fluid absorption of poly(AAm), may enhance wound healing
potential of these hydrogel wound dressings.
PMID- 27506122
TI - Cold-adapted organic solvent tolerant alkalophilic family I.3 lipase from an
Antarctic Pseudomonas.
AB - Lipolytic enzymes with cold adaptation are gaining increasing interest due to
their biotechnological prospective. Previously, a cold adapted family I.3 lipase
(AMS8 lipase) was isolated from an Antarctic Pseudomonas. AMS8 lipase was largely
expressed in insoluble form. The refolded His-tagged recombinant AMS8 lipase was
purified with 23.0% total recovery and purification factor of 9.7. The purified
AMS8 lipase migrated as a single band with a molecular weight approximately 65kDa
via electrophoresis. AMS8 lipase was highly active at 30 degrees C at pH 10. The
half-life of AMS8 lipase was reported at 4 and 2h under the incubation of 30 and
40 degrees C, respectively. The lipase was stable over a broad range of pH. It
showed enhancement effect in its relative activity under the presence of Li+,
Na+, K+, Rb+ and Cs+ after 30min treatment. Heavy metal ions such as Cu2+, Fe3+
and Zn2+ inhibited AMS8 activity. This cold adapted alkalophilic AMS lipase was
also active in various organic solvent of different polarity. These unique
properties of this biological macromolecule will provide considerable potential
for many biotechnological applications and organic synthesis at low temperature.
PMID- 27506123
TI - Resveratrol induces thermal stabilization of human serum albumin and modulates
the early aggregation stage.
AB - Several phenolic compounds bind to proteins and show the ability to interfere
with their aggregation process. The impact of the natural polyphenol resveratrol
on the stability and heat induced aggregation of human serum albumin (HSA) was
investigated by differential scanning calorimetry (DSC), attenuated total
reflectance Fourier transform infrared (ATR-FTIR), UV-vis absorbance, ThT
fluorescence, atomic force microscopy (AFM) and molecular modeling. The binding
of resveratrol to HSA improves the stability of the protein to thermal unfolding,
particularly for the energetic domain containing the ligand binding site, as
modeled by computational techniques. The thermal unfolding is irreversible and
after the melting the protein aggregates, either with or without the ligand. The
kinetics of HSA aggregation between 70 and 80 degrees C shows an exponential
growth of the absorbance change and it slows down when resveratrol is added. The
aggregates have fibril-like morphology and resveratrol attenuates the formation
of beta-structured species. The overall results suggest that resveratrol
stabilizes the protein structure and modulates the formation of fibrils along the
initial stage of the HSA aggregation pathway.
PMID- 27506124
TI - Enhanced removal of cationic dye by calcium alginate/organobentonite beads:
Modeling, kinetics, equilibriums, thermodynamic and reusability studies.
AB - In this study, acid-activated organobentonite (OAB), calcium alginate (A) and
calcium alginate/acid-activated organobentonite composite beads (A-OAB) were
prepared and applied for the removal of methylene blue from solutions in batch
system. The zero point charge of pH (pHpzc), Scanning electron microscopy (SEM)
and Fourier transformed infrared spectroscopy (FTIR) analysis were carried out.
The effects of pH solution (2-11), temperature (15, 25, 35 and 45 degrees C),
initial concentration (20-500mg/L), and contact time were investigated. The
adsorption processes fitted well with the pseudo-second-order kinetic model and
both models Langmuir and Chapman isotherms. Results showed that the maximum
adsorption capacities of (OAB), (A) and (A-OAB) for the adsorption of MB were
263.80, 483.6 and 799.43mg/g at 25 degrees C, respectively. Thermodynamic studies
showed spontaneous and endothermic nature of the overall adsorption process.
Desorption tests showed that the removal efficiency of MB decreased from 95 to
89.7% after six regeneration cycles for (A-OAB). From this, (A-OAB) can be
utilized as an economical adsorbent for the removal of basic dyes from the
contaminated waste water.
PMID- 27506125
TI - Attenuation of thrombosis and bacterial infection using dual function nitric
oxide releasing central venous catheters in a 9day rabbit model.
AB - Two major problems with implanted catheters are clotting and infection. Nitric
oxide (NO) is an endogenous vasodilator as well as natural inhibitor of platelet
adhesion/activation and an antimicrobial agent, and NO-releasing polymers are
expected to have similar properties. Here, NO-releasing central venous catheters
(CVCs) are fabricated using Elast-eonTM E2As polymer with both diazeniumdiolated
dibutylhexanediamine (DBHD/NONO) and poly(lactic-co-glycolic acid) (PLGA)
additives, where the NO release can be modulated and optimized via the hydrolysis
rate of the PLGA. It is observed that using a 10% w/w additive of a PLGA with
ester end group provides the most controlled NO release from the CVCs over a 14d
period. The optimized DBHD/NONO-based catheters are non-hemolytic (hemolytic
index of 0%) and noncytotoxic (grade 0). After 9d of catheter implantation in the
jugular veins of rabbits, the NO-releasing CVCs have a significantly reduced
thrombus area (7 times smaller) and a 95% reduction in bacterial adhesion. These
results show the promise of DBHD/NONO-based NO releasing materials as a solution
to achieve extended NO release for longer term prevention of clotting and
infection associated with intravascular catheters. STATEMENT OF SIGNIFICANCE:
Clotting and infection are significant complications associated with central
venous catheters (CVCs). While nitric oxide (NO) releasing materials have been
shown to reduce platelet activation and bacterial infection in vitro and in short
term animal models, longer-term success of NO-releasing materials to further
study their clinical potential has not been extensively evaluated to date. In
this study, we evaluate diazeniumdiolate based NO-releasing CVCs over a 9d period
in a rabbit model. The explanted NO-releasing CVCs were found to have
significantly reduced thrombus area and bacterial adhesion. These NO-releasing
coatings can improve the hemocompatibility and bactericidal activity of
intravascular catheters, as well as other medical devices (e.g., urinary
catheters, vascular grafts).
PMID- 27506126
TI - Macroporous biohybrid cryogels for co-housing pancreatic islets with mesenchymal
stromal cells.
AB - Intrahepatic transplantation of allogeneic pancreatic islets offers a promising
therapy for type 1 diabetes. However, long-term insulin independency is often not
achieved due to severe islet loss shortly after transplantation. To improve islet
survival and function, extrahepatic biomaterial-assisted transplantation of
pancreatic islets to alternative sites has been suggested. Herein, we present
macroporous, star-shaped poly(ethylene glycol) (starPEG)-heparin cryogel
scaffolds, covalently modified with adhesion peptides, for the housing of
pancreatic islets in three-dimensional (3D) co-culture with adherent mesenchymal
stromal cells (MSC) as accessory cells. The implantable biohybrid scaffolds
provide efficient transport properties, mechanical protection, and a supportive
extracellular environment as a desirable niche for the islets. MSC colonized the
cryogel scaffolds and produced extracellular matrix proteins that are important
components of the natural islet microenvironment known to facilitate matrix-cell
interactions and to prevent cellular stress. Islets survived the seeding
procedure into the cryogel scaffolds and secreted insulin after glucose
stimulation in vitro. In a rodent model, intact islets and MSC could be
visualized within the scaffolds seven days after subcutaneous transplantation.
Overall, this demonstrates the potential of customized macroporous starPEG
heparin cryogel scaffolds in combination with MSC to serve as a multifunctional
islet supportive carrier for transplantation applications. STATEMENT OF
SIGNIFICANCE: Diabetes results in the insufficient production of insulin by the
pancreatic beta-cells in the islets of Langerhans. Transplantation of pancreatic
islets offers valuable options for treating the disease; however, many
transplanted islets often do not survive the transplantation or die shortly
thereafter. Co-transplanted, supporting cells and biomaterials can be
instrumental for improving islet survival, function and protection from the
immune system. In the present study, islet supportive hydrogel sponges were
explored for the co-transplantation of islets and mesenchymal stromal cells.
Survival and continued function of the supported islets were demonstrated in
vitro. The in vivo feasibility of the approach was shown by transplantation in a
mouse model.
PMID- 27506127
TI - Low, but not too low, oxygen tension and macromolecular crowding accelerate
extracellular matrix deposition in human dermal fibroblast culture.
AB - A key challenge of in vitro organogenesis is the development in timely manner
tissue equivalents. Herein, we assessed the simultaneous effect of oxygen tension
(0.5%, 2% and 20%), foetal bovine serum concentration (0.5% and 10%) and
macromolecular crowding (75MUg/ml carrageenan) in human dermal fibroblast
culture. Our data demonstrate that cells cultured at 2% oxygen tension, in the
presence of carrageenan and at 0.5% serum concentration deposited within 3days in
culture more extracellular matrix than cells grown for 14days, at 20% oxygen
tension, 10% serum concentration and in the absence of carrageenan. These data
suggest that optimal oxygen tension coupled with macromolecular crowding are
important in vitro microenvironment modulators for accelerated development of
tissue-like modules in vitro. STATEMENT OF SIGNIFICANCE: To enable clinical
translation and commercialisation of in vitro organogenesis therapies, we
cultured human dermal fibroblast at 2% oxygen tension, under macromolecular
crowding conditions (75MUg/ml carrageenan) and at low foetal bovine serum
concentration (0.5%). Within 3days in culture, more extracellular matrix was
deposited under these conditions than cells grown for 14days, at 20% oxygen
tension, 10% FBS concentration and in the absence of crowding agents. These data
bring us closer to the development of more clinically relevant tissue-like
modules.
PMID- 27506128
TI - On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey.
AB - INTRODUCTION: The number of Alzheimer's Disease (AD) patients is increasing with
increased life expectancy and 115.4 million people are expected to be affected in
2050. Unfortunately, AD is commonly diagnosed too late, when irreversible damages
have been caused in the patient. OBJECTIVE: An automatic, continuous and
unobtrusive early AD detection method would be required to improve patients' life
quality and avoid big healthcare costs. Thus, the objective of this survey is to
review the multimodal signals that could be used in the development of such a
system, emphasizing on the accuracy that they have shown up to date for AD
detection. Some useful tools and specific issues towards this goal will also have
to be reviewed. METHODS: An extensive literature review was performed following a
specific search strategy, inclusion criteria, data extraction and quality
assessment in the Inspec, Compendex and PubMed databases. RESULTS: This work
reviews the extensive list of psychological, physiological, behavioural and
cognitive measurements that could be used for AD detection. The most promising
measurements seem to be magnetic resonance imaging (MRI) for AD vs control (CTL)
discrimination with an 98.95% accuracy, while electroencephalogram (EEG) shows
the best results for mild cognitive impairment (MCI) vs CTL (97.88%) and MCI vs
AD distinction (94.05%). Available physiological and behavioural AD datasets are
listed, as well as medical imaging analysis steps and neuroimaging processing
toolboxes. Some issues such as "label noise" and multi-site data are discussed.
CONCLUSIONS: The development of an unobtrusive and transparent AD detection
system should be based on a multimodal system in order to take full advantage of
all kinds of symptoms, detect even the smallest changes and combine them, so as
to detect AD as early as possible. Such a multimodal system might probably be
based on physiological monitoring of MRI or EEG, as well as behavioural
measurements like the ones proposed along the article. The mentioned AD datasets
and image processing toolboxes are available for their use towards this goal.
Issues like "label noise" and multi-site neuroimaging incompatibilities may also
have to be overcome, but methods for this purpose are already available.
PMID- 27506129
TI - On the development of conjunctival hyperemia computer-assisted diagnosis tools:
Influence of feature selection and class imbalance in automatic gradings.
AB - OBJECTIVE: The sudden increase of blood flow in the bulbar conjunctiva, known as
hyperemia, is associated to a red hue of variable intensity. Experts measure
hyperemia using levels in a grading scale, a procedure that is subjective, non
repeatable and time consuming, thus creating a need for its automatisation.
However, the task is far from straightforward due to data issues such as class
imbalance or correlated features. In this paper, we study the specific features
of hyperemia and propose various approaches to address these problems in the
context of an automatic framework for hyperemia grading. METHODOLOGY:
Oversampling, undersampling and SMOTE approaches were applied in order to tackle
the problem of class imbalance. 25 features were computed for each image and
regression methods were then used to transform them into a value on the grading
scale. The values and relationships among features and experts' values were
analysed, and five feature selection techniques were subsequently studied.
RESULTS: The lowest mean square error (MSE) for the regression systems trained
with individual features is below 0.1 for both scales. Multi-layer perceptron
(MLP) obtains the best values, but is less consistent than the random forest (RF)
method. When all features are combined, the best results for both scales are
achieved with MLP. Correlation based feature selection (CFS) and M5 provide the
best results, MSE=0.108 and MSE=0.061 respectively. Finally, the class imbalance
problem is minimised with the SMOTE approach for both scales (MSE<0.006).
CONCLUSIONS: Machine learning methods are able to perform an objective assessment
of hyperemia grading, removing both intra- and inter-expert subjectivity while
providing a gain in computation time. SMOTE and oversampling approaches minimise
the class imbalance problem, while feature selection reduces the number of
features from 25 to 3-5 without worsening the MSE. As the differences between the
system and a human expert are similar to the differences between experts, we can
therefore conclude that the system behaves like an expert.
PMID- 27506130
TI - Detecting signals of detrimental prescribing cascades from social media.
AB - MOTIVATION: Prescribing cascade (PC) occurs when an adverse drug reaction (ADR)
is misinterpreted as a new medical condition, leading to further prescriptions
for treatment. Additional prescriptions, however, may worsen the existing
condition or introduce additional adverse effects (AEs). Timely detection and
prevention of detrimental PCs is essential as drug AEs are among the leading
causes of hospitalization and deaths. Identifying detrimental PCs would enable
warnings and contraindications to be disseminated and assist the detection of
unknown drug AEs. Nonetheless, the detection is difficult and has been limited to
case reports or case assessment using administrative health claims data. Social
media is a promising source for detecting signals of detrimental PCs due to the
public availability of many discussions regarding treatments and drug AEs.
OBJECTIVE: In this paper, we investigate the feasibility of detecting detrimental
PCs from social media. METHODS: The detection, however, is challenging due to the
data uncertainty and data rarity in social media. We propose a framework to mine
sequences of drugs and AEs that signal detrimental PCs, taking into account the
data uncertainty and data rarity. RESULTS: We conduct experiments on two real
world datasets collected from Twitter and Patient health forum. Our framework
achieves encouraging results in the validation against known detrimental PCs
(F1=78% for Twitter and 68% for Patient) and the detection of unknown potential
detrimental PCs (Precision@50=72% and NDCG@50=95% for Twitter, Precision@50=86%
and NDCG@50=98% for Patient). In addition, the framework is efficient and
scalable to large datasets. CONCLUSION: Our study demonstrates the feasibility of
generating hypotheses of detrimental PCs from social media to reduce pharmacists'
guesswork.
PMID- 27506132
TI - Predicting overlapping protein complexes from weighted protein interaction graphs
by gradually expanding dense neighborhoods.
AB - OBJECTIVE: Proteins are vital biological molecules driving many fundamental
cellular processes. They rarely act alone, but form interacting groups called
protein complexes. The study of protein complexes is a key goal in systems
biology. Recently, large protein-protein interaction (PPI) datasets have been
published and a plethora of computational methods that provide new ideas for the
prediction of protein complexes have been implemented. However, most of the
methods suffer from two major limitations: First, they do not account for
proteins participating in multiple functions and second, they are unable to
handle weighted PPI graphs. Moreover, the problem remains open as existing
algorithms and tools are insufficient in terms of predictive metrics. METHOD: In
the present paper, we propose gradually expanding neighborhoods with adjustment
(GENA), a new algorithm that gradually expands neighborhoods in a graph starting
from highly informative "seed" nodes. GENA considers proteins as multifunctional
molecules allowing them to participate in more than one protein complex. In
addition, GENA accepts weighted PPI graphs by using a weighted evaluation
function for each cluster. RESULTS: In experiments with datasets from
Saccharomyces cerevisiae and human, GENA outperformed Markov clustering,
restricted neighborhood search and clustering with overlapping neighborhood
expansion, three state-of-the-art methods for computationally predicting protein
complexes. Seven PPI networks and seven evaluation datasets were used in total.
GENA outperformed existing methods in 16 out of 18 experiments achieving an
average improvement of 5.5% when the maximum matching ratio metric was used. Our
method was able to discover functionally homogeneous protein clusters and uncover
important network modules in a Parkinson expression dataset. When used on the
human networks, around 47% of the detected clusters were enriched in gene
ontology (GO) terms with depth higher than five in the GO hierarchy. CONCLUSIONS:
In the present manuscript, we introduce a new method for the computational
prediction of protein complexes by making the realistic assumption that proteins
participate in multiple protein complexes and cellular functions. Our method can
detect accurate and functionally homogeneous clusters.
PMID- 27506131
TI - Clinical phenotyping in selected national networks: demonstrating the need for
high-throughput, portable, and computational methods.
AB - OBJECTIVE: The combination of phenomic data from electronic health records (EHR)
and clinical data repositories with dense biological data has enabled genomic and
pharmacogenomic discovery, a first step toward precision medicine. Computational
methods for the identification of clinical phenotypes from EHR data will advance
our understanding of disease risk and drug response, and support the practice of
precision medicine on a national scale. METHODS: Based on our experience within
three national research networks, we summarize the broad approaches to clinical
phenotyping and highlight the important role of these networks in the progression
of high-throughput phenotyping and precision medicine. We provide supporting
literature in the form of a non-systematic review. RESULTS: The practice of
clinical phenotyping is evolving to meet the growing demand for scalable,
portable, and data driven methods and tools. The resources required for
traditional phenotyping algorithms from expert defined rules are significant. In
contrast, machine learning approaches that rely on data patterns will require
fewer clinical domain experts and resources. CONCLUSIONS: Machine learning
approaches that generate phenotype definitions from patient features and clinical
profiles will result in truly computational phenotypes, derived from data rather
than experts. Research networks and phenotype developers should cooperate to
develop methods, collaboration platforms, and data standards that will enable
computational phenotyping and truly modernize biomedical research and precision
medicine.
PMID- 27506133
TI - Medicines optimisation in older people: Taking age and sex into account.
AB - There are a number of complex and seemingly ignored issues around prescribing
safely and effectively for older people, particularly for very old women. These
issues include polypharmacy, possible compliance issues and communication
barriers between patient, specialists and general practitioners (GPs). There are
specific pharmacokinetic (PK) and pharmacodynamic (PD) parameters that change in
older age generally, and in women more specifically, which if ignored are likely
to cause symptoms and to impair quality of life when drug dosage is unchanged.
These changed PK and PD parameters are not all-or-nothing processes, but a
continuum across age, sex and comorbidity. Very old people also have less
'reserve' when drugs are used in 'standard' doses, are more likely to have
multiple concurrent therapies, and the risk of adverse effects of drugs in this
group is very high. Doctors need to consider these issues when providing therapy
for this group, or when trying to unravel the complex prescribing cascade here.
This review outlines general principles to consider when prescribing for older
people, focusing on age- and sex-related changes in both PK and PD processes.
PMID- 27506134
TI - On the permanence of tooth bleaching.
AB - OBJECTIVE: Bleaching (alias whitening) is increasingly the chosen means of
modifying the appearance of teeth for cosmetic reasons. Behbehani et al. (2012)
acquired the largest known data set for the effects of bleaching over time (300
patients for ~1year), but the analysis then was rather superficial and did not
exploit the full depth of information available in it. METHODS: Data collected by
Behbehani et al. (2012) were re-analysed to explore in detail the variation in
outcome between patients and over time. RESULTS: There is a distinct regression
in shade scale value with time, taking something over 1year to approach
stability. There appears to be an intrinsic shade that cannot be altered, at
around 1 unit (0.5M1 on the Vita 3D bleached shade guide). Some patients (11/300
at 1year) appear to be worse-off after treatment, especially those with lighter
starting shades, while many get no real benefit, with a change <=2 units.
SIGNIFICANCE: The effects of bleaching are often transient, but the reversion to
a darker shade than the original may be due to the cumulative damage done to the
organic matrix of enamel. The ethics of the treatment are questioned, as are over
the-counter products and whitening toothpastes. It might be appropriate to
suggest to a patient that there is no point unless the shade is darker than some
(Vita) shade value, say ~1M2, but in any case informed consent is in need of
improvement. All observations of the effects of bleaching ought to be made on
timescales longer than 1year to be meaningful.
PMID- 27506135
TI - Protein expression of preferred human codon-optimized Gaussia luciferase genes
with an artificial open-reading frame in mammalian and bacterial cells.
AB - The protein expressions of three preferred human codon-optimized Gaussia
luciferase genes (pGLuc, EpGLuc, and KpGLuc) were characterized in mammalian and
bacterial cells by comparing them with those of wild-type Gaussia luciferase gene
(wGLuc) and human codon-optimized Gaussia luciferase gene (hGLuc). Two synthetic
genes of EpGLuc and KpGLuc containing the complete preferred human codons have an
artificial open-reading frame; however, they had the similar protein expression
levels to those of pGLuc and hGLuc in mammalian cells. In bacterial cells, the
protein expressions of pGLuc, EpGLuc, and KpGLuc with approximately 65% GC
content were the same and showed approximately 60% activities of wGLuc and hGLuc.
The artificial open-reading frame in EpGLuc and KpGLuc did not affect the protein
expression in mammalian and bacterial cells.
PMID- 27506136
TI - Traffic safety in China: Challenges and countermeasures.
PMID- 27506137
TI - Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda
kappa-immunoglobulins containing HL fragments of antibodies of different
subclasses (IgG1-IgG4).
AB - In the classic paradigm, immunoglobulins represent products of clonal B cell
populations, each producing antibodies recognizing a single antigen
(monospecific). There is a common belief that IgGs in mammalian biological fluids
are monospecific molecules having stable structures and two identical antigen
binding sites. But the issue concerning the possibility of exchange by HL
fragments between the antibody molecules in human blood is still unexplored.
Different physico-chemical and immunological methods for analysis of half
molecule exchange between human blood IgGs were used. Using eighteen blood
samples of healthy humans we have shown unexpected results for the first time:
blood antibodies undergo extensive post-transcriptional half-molecule exchange
and IgG pools on average consist of 62.4 +/- 6.5% IgGs containing kappa light
chains (kappa-kappa-IgGs), 29.8.6 +/- 5.4% lambda light chains (lambda-lambda
IgGs), and 8.8 +/- 2.7% (range 2.6-16.8%) IgGs containing both kappa- and lambda
light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained on average (%):
IgG1 (36.0 and 32.3), IgG2 (50.9 and 51.4), IgG3 (9.7 and 9.9), and IgG4 (6.5 and
5.7), while chimeric kappa-lambda-IgGs consisted of (%): 25.5 +/- 4.2 IgG1, 50.8
+/- 3.9 IgG2, 9.1 +/- 2.1 IgG3, and 14.5 +/- 2.2 IgG4. Our unexpected data are
indicative of the possibility of half-molecule exchange between blood IgGs of
various subclasses, raised against different antigens. The existence of blood
chimeric bifunctional IgGs with different binding sites destroys the classic
paradigm. Due to the phenomenon of polyspecificity and cross-reactivity of
bifunctional IgGs containing HL-fragments of different types to different
antigens, such IgGs may be important in human blood for widening their different
biological functions.
PMID- 27506138
TI - Evaluation of serum levels of IL-9 and IL-17 in human Schistosoma mansoni
infection and their relationship with periportal fibrosis.
AB - Serum levels of IL-9 and IL-17 cytokines were evaluated in patients in the acute,
chronic phases and clinical forms of human schistosomiasis and in different
classifications of periportal fibrosis. No significant differences between the
groups of the disease with serum levels of cytokine were found. However, this
study discusses the results of some cytokines that have not fully defined roles
in the pathology of human schistosomiasis. Furthermore, an examination was made
of subjects in the acute phase. This is an important group that is difficult to
identify in areas where the disease is endemic. More studies are being undertaken
to study the role of IL-9 and IL-17 in human Schistosoma mansoni infection and
their relationship with the immunopathogenesis of disease.
PMID- 27506139
TI - Plasma enhanced vortex fluidic device manipulation of graphene oxide.
AB - A vortex fluid device (VFD) with non-thermal plasma liquid processing within
dynamic thin films has been developed. This plasma-liquid microfluidic platform
facilitates chemical processing which is demonstrated through the manipulation of
the morphology and chemical character of colloidal graphene oxide in water.
PMID- 27506140
TI - Alternative to Ph. Eur. pour-plate method for detection of microbial
contamination in non-sterile pharmaceutical preparations.
AB - The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2
include a nonspecific photometric protein assay using albumin as calibrator and a
highly variable cell-based assay for the potency determination of the protective
effects. A request was expressed by the Official Medicines Control Laboratories
(OMCLs) for improved methods for the batch control of recombinant interferon alfa
2 bulk and market surveillance testing of finished products, including those
formulated with Human Serum Albumin (HSA). A HPLC method was developed at the
Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An
initial collaborative study run under the Biological Standardisation Programme
(BSP; study code BSP039) revealed the need for minor changes to improve linearity
of the calibration curves, assay reproducibility and robustness. The goal of the
collaborative study, coded BSP071, was to transfer and further validate this
improved HPLC method. Ten laboratories participated in the study. Four marketed
IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical
Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference
standards from two manufacturers were used for the quantitative assay. The
modified method was successfully transferred to all laboratories despite local
variation in equipment. The resolution between the main and the oxidised forms of
IFN-alfa-2 was improved compared to the results from the BSP039 study. The
improved method even allowed partial resolution of an extra peak after the
principal peak. Symmetry of the main IFN peak was acceptable for all samples in
all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a
and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the
origin and coefficients of determination greater than 0.9995. Assay
repeatability, intermediate precision and reproducibility varied with the tested
sample within acceptable ranges. Test accuracy estimated by comparing the values
obtained by the participants to the declared contents determined by the
manufacturers was good despite the absence of a common reference preparation. In
conclusion, the present study showed that the new method is suitable,
reproducible and transferable. Proposals for the revision of Ph. Eur. texts are
presented.
PMID- 27506141
TI - Characterization of gray matter atrophy following 6-hydroxydopamine lesion of the
nigrostriatal system.
AB - BACKGROUND: The unilaterally-lesioned 6-hydroxydopamine (6-OHDA) rat is one of
the most commonly used experimental models of Parkinson's disease (PD). Here we
investigated whether magnetic resonance imaging (MRI) that is widely used in
human PD research, has the potential to non-invasively detect macroscopic
structural brain changes in the 6-OHDA rat in ways translatable to humans.
METHODS: We measured the gray matter (GM) composition in the unilateral 6-OHDA
rat in comparison to sham animals using whole-brain voxel-based morphometry (VBM)
- an unbiased MR image analysis technique. The number of nigral dopamine (DA)
neurons and the density of their cortical projections were examined post-mortem
using immunohistochemistry. RESULTS: VBM revealed widespread bilateral changes in
gray matter volume (GMV) on a topographic scale in the brains of 6-OHDA rats,
compared to sham-operated rats. The greatest changes were in the lesioned
hemisphere, which displayed reductions of GMV in motor, cingulate and
somatosensory cortex. Histopathological results revealed dopaminergic cell loss
in the substantia nigra (SN) and a denervation in the striatum, as well as in the
frontal, somatosensory and cingulate cortices. CONCLUSION: Unilateral
nigrostriatal 6-OHDA lesioning leads to widespread GMV changes, which extend
beyond the nigrostriatal system and resemble advanced Parkinsonism. This study
highlights the potential of structural MRI, and VBM in particular, for the system
level phenotyping of rodent models of Parkinsonism and provides a methodological
framework for future studies in novel rodent models as they become available to
the research community.
PMID- 27506142
TI - Building brains in a dish: Prospects for growing cerebral organoids from stem
cells.
AB - The recent development of organoid techniques, in which embryonic brain-like
tissue can be grown from human or mouse stem cells in vitro offers the potential
to transform the way in which brain development is studied. In this review, we
summarize key aspects of the embryonic development of mammalian forebrains,
focussing in particular on the cerebral cortex and highlight significant
differences between mouse and primates, including human. We discuss recent work
using cerebral organoids that has revealed key similarities and differences
between their development and that of the brain in vivo. Finally, we outline the
ways in which cerebral organoids can be used in combination with CRISPR/Cas9
genome editing to unravel genetic mechanisms that control embryonic development
of the cerebral cortex, how this can help us understand the causes of
neurodevelopmental disorders and some of the key challenges which will have to be
resolved before organoids can become a mainstream tool to study brain
development.
PMID- 27506143
TI - Rapid CO breath test screening of drugs for protective effects on ribavirin
induced hemolysis in a rabbit model: a pilot study.
AB - Hemolytic anemia is a major side effect of ribavirin antiviral treatment for
chronic hepatitis C. Ribavirin dose reduction may compromise the antiviral
response and erythropoietin can take several weeks to alleviate anemia. The
purpose of the present study was to screen potentially protective drugs against
ribavirin-induced hemolytic anemia in a rabbit model, using our modified CO
breath test for measuring erythrocyte (RBC) lifespan, the gold standard
diagnostic index of hemolysis. Fifteen rabbits were divided randomly into five
groups (N = 3/group): one vehicle control group, one ribavirin (only)-treated
(RBV) group, and three groups initially treated with ribavirin only, followed by
a combination of ribavirin with prednisone (RBV + Pred), polyene phosphatidyl
choline (RBV + PPC), or reduced glutathione (RBV + GSH). RBC lifespan was
calculated from accumulated CO measured in a closed rebreath apparatus, blood
volume measured by the Evan's blue dye (EBD) dilution test, and hemoglobin
concentration data. The RBC lifespan was normal in the vehicle control group (44
60 d), but reduced significantly in all of the ribavirin-treated groups before
the addition of screened drugs (17-35 d). RBC lifespan rebounded significantly
with the addition of glutathione, but not with the addition of prednisone or
polyene phosphatidyl choline. A similar overall drug effect pattern was seen in
the hemoglobin concentration and reticulocyte count data. In conclusion, the
results of this pilot study indicate that reduced glutathione can attenuate
ribavirin-induced hemolytic anemia, and that the RBC lifespan measured with our
modified rapid CO breath test is feasible and reliable for use in animal studies.
PMID- 27506144
TI - Validating the extract, transform, load process used to populate a large clinical
research database.
AB - BACKGROUND: Informaticians at any institution that are developing clinical
research support infrastructure are tasked with populating research databases
with data extracted and transformed from their institution's operational
databases, such as electronic health records (EHRs). These data must be properly
extracted from these source systems, transformed into a standard data structure,
and then loaded into the data warehouse while maintaining the integrity of these
data. We validated the correctness of the extract, load, and transform (ETL)
process of the extracted data of West Virginia Clinical and Translational Science
Institute's Integrated Data Repository, a clinical data warehouse that includes
data extracted from two EHR systems. METHODS: Four hundred ninety-eight
observations were randomly selected from the integrated data repository and
compared with the two source EHR systems. RESULTS: Of the 498 observations, there
were 479 concordant and 19 discordant observations. The discordant observations
fell into three general categories: a) design decision differences between the
IDR and source EHRs, b) timing differences, and c) user interface settings. After
resolving apparent discordances, our integrated data repository was found to be
100% accurate relative to its source EHR systems. CONCLUSION: Any institution
that uses a clinical data warehouse that is developed based on extraction
processes from operational databases, such as EHRs, employs some form of an ETL
process. As secondary use of EHR data begins to transform the research landscape,
the importance of the basic validation of the extracted EHR data cannot be
underestimated and should start with the validation of the extraction process
itself.
PMID- 27506145
TI - Epigenetic regulation of redox state mediates persistent cardiorespiratory
abnormalities after long-term intermittent hypoxia.
AB - KEY POINTS: The effects of short-term (ST; 10 days) and long-term (LT; 30 days)
intermittent hypoxia (IH) on blood pressure (BP), breathing and carotid body (CB)
chemosensory reflex were examined in adult rats. ST- and LT-IH treated rats
exhibited hypertension, irregular breathing with apnoea and augmented the CB
chemosensory reflex, with all these responses becoming normalized during recovery
from ST- but not from LT-IH. The persistent cardiorespiratory responses to LT-IH
were associated with elevated reactive oxygen species (ROS) levels in the CB and
adrenal medulla, which were a result of DNA methylation-dependent suppression of
genes encoding anti-oxidant enzymes (AOEs). Treating rats with decitabine either
during LT-IH or during recovery from LT-IH prevented DNA methylation of AOE
genes, normalized the expression of AOE genes and ROS levels, reversed the
heightened CB chemosensory reflex and hypertension, and also stabilized
breathing. ABSTRACT: Rodents exposed to chronic intermittent hypoxia (IH),
simulating blood O2 saturation profiles during obstructive sleep apnoea (OSA),
have been shown to exhibit a heightened carotid body (CB) chemosensory reflex and
hypertension. CB chemosensory reflex activation also results in unstable
breathing with apnoeas. However, the effect of chronic IH on breathing is not
known. In the present study, we examined the effects of chronic IH on breathing
along with blood pressure (BP) and assessed whether the autonomic responses are
normalized after recovery from chronic IH. Studies were performed on adult, male,
Sprague-Dawley rats exposed to either short-term (ST; 10 days) or long-term (LT,
30 days) IH. Rats exposed to either ST- or LT-IH exhibited hypertension,
irregular breathing with apnoeas, an augmented CB chemosensory reflex as
indicated by elevated CB neural activity and plasma catecholamine levels, and
elevated reactive oxygen species (ROS) levels in the CB and adrenal medulla (AM).
All these effects were normalized after recovery from ST-IH but not from LT-IH.
Analysis of the molecular mechanisms underlying the persistent effects of LT-IH
revealed increased DNA methylation of genes encoding anti-oxidant enzymes (AOEs).
Treatment with decitabine, a DNA methylation inhibitor, either during LT-IH or
during recovery from LT-IH, prevented DNA methylation, normalized the expression
of AOE genes, ROS levels, CB chemosensory reflex and BP, and also stabilized
breathing. These results suggest that persistent cardiorespiratory abnormalities
caused by LT-IH are mediated by epigenetic re-programming of the redox state in
the CB chemosensory reflex pathway.
PMID- 27506147
TI - Metallic-like bonding in plasma-born silicon nanocrystals for nanoscale bandgap
engineering.
AB - Based on ab initio molecular dynamics simulations, we show that small
nanoclusters of about 1 nm size spontaneously generated in a low-temperature
silane plasma do not possess tetrahedral structures, but are ultrastable.
Apparently small differences in the cluster structure result in substantial
modifications in their electric, magnetic, and optical properties, without the
need for any dopants. Their non-tetrahedral geometries notably lead to electron
deficient bonds that introduce efficient electron delocalization that strongly
resembles the one of a homogeneous electron gas leading to metallic-like bonding
within a semiconductor nanocrystal. As a result, pure hydrogenated silicon
clusters that form by self-assembly in a plasma reactor possess optical gaps
covering most of the solar spectrum from 1.0 eV to 5.2 eV depending simply on
their structure and, in turn, on their degree of electron delocalization. This
feature makes them ideal candidates for future bandgap engineering not only for
photovoltaics, but also for many nano-electronic devices employing nothing else
but silicon and hydrogen atoms.
PMID- 27506146
TI - CCBE1 promotes GIST development through enhancing angiogenesis and mediating
resistance to imatinib.
AB - Gastrointestinal stromal tumor (GIST) is the most major mesenchymal neoplasm of
the digestive tract. Up to now, imatinib mesylate has been used as a standard
first-line treatment for irresectable and metastasized GIST patients or adjuvant
treatment for advanced GIST patients who received surgical resection. However,
secondary resistance to imatinib usually happens, resulting in a major obstacle
in GIST successful therapy. In this study, we first found that collagen and
calcium binding EGF domains 1 (CCBE1) expression gradually elevated along with
the risk degree of NIH classification, and poor prognosis emerged in the CCBE1
positive patients. In vitro experiments showed that recombinant CCBE1 protein can
enhance angiogenesis and neutralize partial effect of imatinib on the GIST-T1
cells. In conclusion, these data indicated that CCBE1 may be served as a new
predictor of prognosis in post-operative GIST patients and may play an important
role in stimulating GIST progression.
PMID- 27506148
TI - Incorporating Novel Mobile Health Technologies Into Management of Knee
Osteoarthritis in Patients Treated With Intra-Articular Hyaluronic Acid:
Rationale and Protocol of a Randomized Controlled Trial.
AB - BACKGROUND: Osteoarthritis (OA) of the knee is one of the leading causes of
disability in the United States. One relatively new strategy that could be
helpful in the management of OA is the use of mHealth technologies, as they can
be used to increase physical activity and promote exercise, which are key
components of knee OA management. OBJECTIVE: Currently, no published data on the
use of a mHealth approach to comprehensively monitor physical activity in
patients with OA are available, and similarly, no data on whether mHealth
technologies can impact outcomes are available. Our objective is to evaluate the
effectiveness of mHealth technology as part of a tailored, comprehensive
management strategy for patients with knee OA. METHODS: The study will assess the
impact of a smartphone app that integrates data from a wearable activity monitor
(thereby both encouraging changes in mobility as well as tracking them) combined
with education about the benefits of walking on patient mobility. The results
from the intervention group will be compared with data from a control group of
individuals who are given the same Arthritis Foundation literature regarding the
benefits of walking and wearable activity monitors but who do not have access to
the data from those monitors. Activity monitors will capture step count estimates
and will compare those with patients' step goals, calories burned, and distance
walked. Patients using the novel smartphone app will be able to enter information
on their daily pain, mood, and sleep quality. The relationships among activity
and pain, activity and mood, and sleep will be assessed, as will patient
satisfaction with and adherence to the mobile app. RESULTS: We present
information on an upcoming trial that will prospectively assess the ability of a
mobile app to improve mobility for knee OA patients who are treated with intra
articular hyaluronic acid. CONCLUSIONS: We anticipate the results of this study
will support the concept that mHealth technologies provide continuous, real-time
feedback to patients with OA on their overall level of activity for a more
proactive, personalized approach to treatment that may help modify behavior and
assist with self-management through treatment support in the form of motivational
messages and reminders.
PMID- 27506151
TI - Skin prick test and development of tolerance in egg allergy.
PMID- 27506149
TI - Phytochrome B and REVEILLE1/2-mediated signalling controls seed dormancy and
germination in Arabidopsis.
AB - Seeds maintain a dormant state to withstand adverse conditions and germinate when
conditions become favourable to give rise to a new generation of flowering
plants. Seed dormancy and germination are tightly controlled by internal and
external signals. Although phytochrome photoreceptors are proposed to regulate
primary seed dormancy, the underlying molecular mechanism remains elusive. Here
we show that the REVEILLE1 (RVE1) and RVE2 transcription factors promote primary
seed dormancy and repress red/far-red-light-reversible germination downstream of
phytochrome B (phyB) in Arabidopsis thaliana. RVE1 and RVE2 expression is
downregulated after imbibition and by phyB. RVE1 directly binds to the promoter
of GIBBERELLIN 3-OXIDASE 2, inhibits its transcription and thus suppresses the
biosynthesis of bioactive gibberellins. In addition, DELAY OF GERMINATION 1 also
acts downstream of phyB. This study identifies a signalling pathway that
integrates environmental light input with internal factors to control both seed
dormancy and germination.
PMID- 27506150
TI - Amylose engineering: phosphorylase-catalyzed polymerization of functional
saccharide primers for glycobiomaterials.
AB - Interest in amylose and its hybrids has grown over many decades, and a great deal
of work has been devoted to developing methods for designing functional amylose
hybrids. In this context, phosphorylase-catalyzed polymerization shows
considerable promise as a tool for preparing diverse amylose hybrids. Recently,
advances have been made in the chemoenzymatic synthesis and characterization of
amylose-block-polymers, amylose-graft-polymers, amylose-modified surfaces, hetero
oligosaccharides, and cellodextrin hybrids. Many of these saccharides provide
clear opportunities for advances in biomaterials because of their
biocompatibility and biodegradability. Important developments in bioapplications
of amylose hybrids have also been made, and such newly developed amylose hybrids
will help promote the development of new generations of glyco materials. WIREs
Nanomed Nanobiotechnol 2017, 9:e1423. doi: 10.1002/wnan.1423 For further
resources related to this article, please visit the WIREs website.
PMID- 27506152
TI - Optical characterization of Tm(3+) doped Bi2O3-GeO2-Ga2O3 glasses in absence and
presence of BaF2.
AB - In this paper, Two new Bi2O3-GeO2-Ga2O3 glasses (one presence of BaF2) doped with
1mol% Tm2O3 were prepared by melt-quenching technique. Differential thermal
analysis (DTA), the absorption, Raman, IR spectra and fluorescence spectra were
measured. The Judd-Ofelt intensity parameters, emission cross section, absorption
cross section, and gain coefficient of Tm(3+) ions were comparatively
investigated. After the BaF2 introduced, the glass showed a better thermal
stability, lower phonon energy and weaker OH(-) absorption coefficient,
meanwhile, a larger ~1.8 MUm emission cross section sigmaem (7.56 * 10(-21)
cm(2)) and a longer fluorescence lifetime taumea (2.25 ms) corresponding to the
Tm(3+): (4)F3 -> (3)H6 transition were obtained, which is due to the addition of
fluoride in glass could reduce the quenching rate of hydroxyls and raise the
cross-relaxation ((3)H6 + (3)H4 -> (3)F4 + (3)F4) rate. Our results suggest that
the Tm(3+) doped Bi2O3-GeO2-Ga2O3 glass with BaF2 might be potential to the
application in efficient ~1.8 MUm lasers system.
PMID- 27506153
TI - Custom Map Projections for Regional Groundwater Models.
AB - For regional groundwater flow models (areas greater than 100,000 km2 ), improper
choice of map projection parameters can result in model error for boundary
conditions dependent on area (recharge or evapotranspiration simulated by
application of a rate using cell area from model discretization) and length
(rivers simulated with head-dependent flux boundary). Smaller model areas can use
local map coordinates, such as State Plane (United States) or Universal
Transverse Mercator (correct zone) without introducing large errors. Map
projections vary in order to preserve one or more of the following properties:
area, shape, distance (length), or direction. Numerous map projections are
developed for different purposes as all four properties cannot be preserved
simultaneously. Preservation of area and length are most critical for groundwater
models. The Albers equal-area conic projection with custom standard parallels,
selected by dividing the length north to south by 6 and selecting standard
parallels 1/6th above or below the southern and northern extent, preserves both
area and length for continental areas in mid latitudes oriented east-west. Custom
map projection parameters can also minimize area and length error in non-ideal
projections. Additionally, one must also use consistent vertical and horizontal
datums for all geographic data. The generalized polygon for the Floridan aquifer
system study area (306,247.59 km2 ) is used to provide quantitative examples of
the effect of map projections on length and area with different projections and
parameter choices. Use of improper map projection is one model construction
problem easily avoided.
PMID- 27506154
TI - Mycotic Aneurysm of the Abdominal Aorta Complicated With Iliopsoas Abscess and
Infectious Spondylodiscitis in a Long-Term Hemodialyzed Patient: A Rare but
Serious Complication of Staphylococcus Aureus Bacteremia.
PMID- 27506155
TI - Crude oil exposures reveal roles for intracellular calcium cycling in haddock
craniofacial and cardiac development.
AB - Recent studies have shown that crude oil exposure affects cardiac development in
fish by disrupting excitation-contraction (EC) coupling. We previously found that
eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets,
potentially leading to more profound toxic effects from uptake of polycyclic
aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil
(0.7-7 MUg/L ?PAH), here we exposed a broader range of developmental stages over
both short and prolonged durations. We quantified effects on cardiac function and
morphogenesis, characterized novel craniofacial defects, and examined the
expression of genes encoding potential targets underlying cardiac and
craniofacial defects. Because of oil droplet binding, a 24-hr exposure was
sufficient to create severe cardiac and craniofacial abnormalities. The specific
nature of the craniofacial abnormalities suggests that crude oil may target
common craniofacial and cardiac precursor cells either directly or indirectly by
affecting ion channels and intracellular calcium in particular. Furthermore, down
regulation of genes encoding specific components of the EC coupling machinery
suggests that crude oil disrupts excitation-transcription coupling or normal
feedback regulation of ion channels blocked by PAHs. These data support a
unifying hypothesis whereby depletion of intracellular calcium pools by crude oil
derived PAHs disrupts several pathways critical for organogenesis in fish.
PMID- 27506156
TI - Variability in the number of abdominal leucokinergic neurons in adult Drosophila
melanogaster.
AB - Developmental plasticity allows individuals with the same genotype to show
different phenotypes in response to environmental changes. An example of this is
how neuronal diversity is protected at the expense of neuronal number under
sustained undernourishment during the development of the Drosophila optic lobe.
In the development of the Drosophila central nervous system, neuroblasts go
through two phases of neurogenesis separated by a period of mitotic quiescence.
Although during embryonic development much evidence indicates that both cell
number and the cell fates generated by each neuroblast are very precisely
controlled in a cell autonomous manner, after quiescence extrinsic factors
control the reactivation of neuroblast proliferation in a fashion that has not
yet been elucidated. Moreover, there is very little information about whether
environmental changes affect lineage progression during postembryonic
neurogenesis. Using as a model system the pattern of abdominal leucokinergic
neurons (ABLKs), we have analyzed how changes in a set of environmental factors
affect the number of ABLKs generated during postembryonic neurogenesis. We
describe the variability in ABLK number between individuals and between
hemiganglia of the same individual and, by genetic analysis, we identify the
bithorax-complex genes and the ecdysone hormone as critical factors in these
differences. We also explore the possible adaptive roles involved in this
process. J. Comp. Neurol. 525:639-660, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27506157
TI - Immune tolerance in pediatric solid organ transplant through allogeneic
hematopoietic stem cell transplant and a solid organ/liver transplant from the
same donor.
PMID- 27506158
TI - PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid
Rafts in Extracellular Vesicles.
AB - Prostaglandin E2 (PGE2 )-initiated signaling contributes to stem cell homeostasis
and regeneration. However, it is unclear how PGE2 signaling controls cell
stemness. This study identifies a previously unknown mechanism by which PGE2
/prostaglandin E receptor 4 (EP4 ) signaling regulates multiple signaling
pathways (e.g., PI3K/Akt signaling, TGFbeta signaling, Wnt signaling, EGFR
signaling) which maintain the basal mammary stem cell phenotype. A shift of basal
mammary epithelial stem cells (MaSCs) from a mesenchymal/stem cell state to a non
basal-MaSC state occurs in response to prostaglandin E receptor 4 (EP4 )
antagonism. EP4 antagonists elicit release of signaling components, by
controlling their trafficking into extracellular vesicles/exosomes in a lipid
raft/caveolae-dependent manner. Consequently, EP4 antagonism indirectly
inactivates, through induced extracellular vesicle/exosome release, pathways
required for mammary epithelial stem cell homeostasis, e.g.
canonical/noncanonical Wnt, TGFbeta and PI3K/Akt pathways. EP4 antagonism causes
signaling receptors and signaling components to shift from non-lipid raft
fractions to lipid raft fractions, and to then be released in EP4 antagonist
induced extracellular vesicles/exosomes, resulting in the loss of the stem cell
state by mammary epithelial stem cells. In contrast, luminal mammary epithelial
cells can acquire basal stem cell properties following ingestion of EP4
antagonist-induced stem cell extracellular vesicles/exosomes, and can then form
mammary glands. These findings demonstrate that PGE2 /EP4 signaling controls
homeostasis of mammary epithelial stem cells through regulating extracellular
vesicle/exosome release. Reprogramming of mammary epithelial cells can result
from EP4 -mediated stem cell property transfer by extracellular vesicles/exosomes
containing caveolae-associated proteins, between mammary basal and luminal
epithelial cells. Stem Cells 2017;35:425-444.
PMID- 27506159
TI - Voltage controlled core reversal of fixed magnetic skyrmions without a magnetic
field.
AB - Using micromagnetic simulations we demonstrate core reversal of a fixed magnetic
skyrmion by modulating the perpendicular magnetic anisotropy of a nanomagnet with
an electric field. We can switch reversibly between two skyrmion states and two
ferromagnetic states, i.e. skyrmion states with the magnetization of the core
pointing down/up and periphery pointing up/down, and ferromagnetic states with
magnetization pointing up/down, by sequential increase and decrease of the
perpendicular magnetic anisotropy. The switching between these states is
explained by the fact that the spin texture corresponding to each of these stable
states minimizes the sum of the magnetic anisotropy, demagnetization,
Dzyaloshinskii-Moriya interaction (DMI) and exchange energies. This could lead to
the possibility of energy efficient nanomagnetic memory and logic devices
implemented with fixed skyrmions without using a magnetic field and without
moving skyrmions with a current.
PMID- 27506160
TI - Photolysis of a bola-type supra-amphiphile promoted by water-soluble
pillar[5]arene-induced assembly.
AB - A bola-type supra-amphiphile assembled from a water-soluble pillar[5]arene host
(WP5) and a rod-coil guest molecule (G) containing a photoactive 9,10
dialkoxyanthracene group was successfully constructed, which could further
assemble into a monolayer supramolecular vesicle. Interestingly, the
photodecomposition rate of G was remarkably promoted after its aggregation with
WP5, accompanied by the disassembly of the formed supramolecular vesicle,
especially with the coassembly of a photosensitizer eosin Y, which has potential
applications in phototherapy.
PMID- 27506161
TI - Sauropsids Cornification is Based on Corneous Beta-Proteins, a Special Type of
Keratin-Associated Corneous Proteins of the Epidermis.
AB - The evolution of the process of cornification in amniote epidermis from the
general process of keratinization present in simple epithelia of anamniotes took
place through the evolution of specialized intermediate filament (alpha)
keratins, keratin-associated proteins (KAPs) and corneous proteins (CPs). The
scanty information on the three-dimensional conformation of known KAPs and CPs
indicate these proteins contain alpha-helix, random coiled, or beta sheets with
different lengths and organizations. CP genes originated in a chromosome locus
indicated as epidermal differentiation complex (EDC), and transformed the
epidermal keratinization of anamniotes into the cornified epidermis and skin
appendages of amniotes (claws, beaks, and feathers). In particular, peculiar
genes encoding for small proteins with a central region of 34 amino acids
conformed as beta sheets were originated in the EDC of sauropsids (reptiles and
birds). These proteins were traditionally indicated as beta-keratins because they
form filaments of 3-4 nm in diameter and show an X-ray beta pattern. Different
from other proteins of the EDC, dimers of these corneous beta-proteins associate
into long polymers of filamentous proteins utilized in sauropsids skin
appendages, such as scales and feathers. Future challenges in this area of
research will be the study on gene regulation and expression for these proteins,
their origin and evolution in different lineages of sauropsids, and their role in
determining the material properties of sauropsid scales and other skin
appendages.
PMID- 27506162
TI - (1)H NMR spectroscopic elucidation in solution of the kinetics and thermodynamics
of spin crossover for an exceptionally robust Fe(2+) complex.
AB - A series of Fe(2+) spin crossover (SCO) complexes [Fe(5/6)](2+) employing
hexadentate ligands (5/6) with cis/trans-1,2-diamino cyclohexanes (4) as central
building blocks were synthesised. The ligands were obtained by reductive
amination of 4 with 2,2'-bipyridyl-6-carbaldehyde or 1,10-phenanthroline-2
carbaldehyde 3. The chelating effect and the rigid structure of the ligands 5/6
lead to exceptionally robust Fe(2+) and Zn(2+) complexes conserving their
structure even in coordinating solvents like dmso at high temperatures. Their
solution behavior was investigated using variable temperature (VT) (1)H NMR
spectroscopy and VT Vis spectroscopy. SCO behavior was found for all Fe(2+)
complexes in this series centred around and far above room temperature. For the
first time we have demonstrated that the thermodynamics as well as kinetics for
SCO can be deduced by using VT (1)H NMR spectroscopy. An alternative scheme using
a linear correction term C(1) to model chemical shifts for Fe(2+) SCO complexes
is presented. The rate constant for the SCO of [Fe(rac-trans-5)](2+) obtained by
VT (1)H NMR was validated by Laser Flash Photolysis (LFP), with excellent
agreement (1/(kHL + kLH) = 33.7/35.8 ns for NMR/LFP). The solvent dependence of
the transition temperature T1/2 and the solvatochromism of complex [Fe(rac-trans
5)](2+) were ascribed to hydrogen bond formation of the secondary amine to the
solvent. Enantiomerically pure complexes can be prepared starting with R,R- or
S,S-1,2-diaminocyclohexane (R,R-trans-4 or S,S-trans-4). The high robustness of
the complexes reduces a possible ligand scrambling and allows preparation of
quasiracemic crystals of [Zn(R,R-5)][Fe(S,S-5)](ClO4)4.(CH3CN) composed of a 1 :
1 mixture of the Zn and Fe complexes with inverse chirality.
PMID- 27506163
TI - Interaction of Staphylococcus aureus persister cells with the host when in a
persister state and following awakening.
AB - Persister cells, a tolerant cell sub-population, are commonly associated with
chronic and recurrent infections. However, little is known about their ability to
actually initiate or establish an infection, become virulent and cause
pathogenicity within a host. Here we investigated whether Staphylococcus aureus
persister cells initiate an infection and are recognized by macrophages, while in
a persister cell status, and upon awakening due to exposure to cis-2-decenoic
acid (cis-DA). Our results show that S. aureus persister cells are not able to
initiate infections in A. thaliana and present significantly reduced virulence
towards C. elegans compared to total populations. In contrast, awakened S. aureus
persister cells are able to initiate infections in A. thaliana and in C. elegans
albeit, with lower mortality than total population. Furthermore, exposure of S.
aureus persister cells to cis-DA led to a loss of tolerance to ciprofloxacin, and
an increase of the bacterial fluorescence to levels found in total population. In
addition, macrophage engulfment of persister cells was significantly lower than
engulfment of total population, both before and following awakening. Overall our
findings indicate that upon awakening of a persister population the cells regain
their ability to infect hosts despite the absence of an increased immune
response.
PMID- 27506164
TI - Preliminary Data on a Care Coordination Program for Home Care Recipients.
AB - Home care recipients are often hospitalized for potentially avoidable reasons. A
pilot program (Intervention in Home Care to Improve Health Outcomes (In-Home))
was designed to help home care providers identify acute clinical changes in
condition and then manage the condition in the home and thereby avoid a costly
hospitalization. Caregivers answer simple questions about the care recipient's
condition during a telephone-based "clock-out" at the end of each shift.
Responses are electronically captured in the agency management software that
caregivers use to "clock-in," manage care, and "clock-out" on every shift. These
are transmitted to the agency's care manager, who follows up on the change in
condition and escalates appropriately. A description of the In-Home model is
presented, and pilot data from 22 home care offices are reported. In the pilot,
caregivers reported a change in condition after 2% of all shifts, representing an
average of 1.9 changes per care recipient in a 6-month period. Changes in
behavior and skin condition were the most frequently recorded domains. Interviews
with participating caregivers and care managers suggested positive attitudes
regarding the intervention; challenges included resistance to change on the part
of home care staff and difficulties in applying a uniform intervention to
individuals with varying needs in home care offices with varying capacities. In
an ongoing randomized trial, the success of the overall program will be measured
primarily according to the potential reduction in avoidable hospitalizations of
home care recipients and the effect this potential reduction has on spending and
healthcare outcomes.
PMID- 27506165
TI - Are oxidative stress markers associated with unexplained male infertility?
AB - Male infertility can be responsible for up to 20% of the cases attending
fertility consultation facilities; nonetheless, the underlying molecular
mechanisms that could explain it are still elusive. Therefore, we aimed to
evaluate conventional and functional parameters of semen samples from patients
who presented with male infertility of unknown origin. Conventional semen
parameters and functional parameters (i.e. intracellular reactive oxygen species
production, mitochondrial membrane potential, sperm chromatin structure assay,
sperm membrane lipid peroxidation and antioxidant capacity of seminal plasma)
were evaluated on semen samples from 54 healthy donors, 23 patients with
idiopathic infertility and 34 fertile controls. No significant differences were
observed in the conventional seminal parameters between the fertile and infertile
men. However, increased intracellular reactive oxygen species (ROS) production
and DNA fragmentation were observed in the infertile patients compared to the
fertile group. Alterations in intracellular ROS production and DNA fragmentation
could be associated with male idiopathic infertility. These parameters could
eventually distinguish both groups more accurately than the conventional
parameters. Our current results are encouraging, and the efficacy of these
parameters in the clinical settings needs to be further assessed to establish
their predictive potential as a marker of unexplained male infertility.
PMID- 27506166
TI - Renal Doppler Indices in Children with Nephrotic Syndrome: Findings from a
Tertiary Hospital in Nigeria.
AB - The resistive and pulsatility indices are known tools for assessing renal
function in kidney diseases, especially in proteinuric conditions like Paediatric
Nephrotic syndrome (NS) which is a glomerular disease. However, there is a
limited knowledge in the use of Doppler Resistive and pulsatility indices in the
management of this disease condition. This was a case control study involving 53
cases and 57 controls. The Doppler parameters, resistive index (RI) and
pulsatility index (PI) of the renal interlobar arteries were determined for the
upper, middle, and lower poles bilaterally for both controls and cases. The mean
RI on the right and left were 0.59 +/- 0.06 and 0.58 +/- 0.06 respectively for
the NS cases whereas for the controls it was 0.61 +/- 0.05 and 0.60 +/- 0.04 on
the right and left respectively. The mean PI on the right and left measured 0.96
+/- 0.16 and 0.94 +/- 0.15 respectively for the NS cases while that for the
control cases measured 0.98 +/- 0.13.and 0.95 +/- 0.12 on the right and left
respectively. Although, the interlobar arteries mean RIs were generally less than
that for the controls, but only the left middle pole showed statistically
significant mean difference (p= 0.004). There was also statistically significant
mean difference (p= 0.048) between the cases and controls in the left middle pole
PI. However, no correlation was found when the renal RI and PI are compared with
the serum albumin and creatinine. Although there was no statistical significance
between the mean RI and PI of the NS cases and controls, except in the left
middle pole RI, it is recommended that Doppler ultrasound should still be part of
management of Nephrotic syndrome patients especially those who have developed end
stage renal disease in order to monitor their renal function.
PMID- 27506167
TI - Spinal Cord Studies in the African Giant Rat (Cricetomys gambianus, Waterhouse).
AB - The African giant rat, AGR, is known for advantageous behavioural patterns among
which are cognition and dexterous locomotion. This study investigated the
morphological, morphometric and possible functional aspects of the AGR spinal
cord (SC) anatomy. Ten adult (5 males and 5 females) AGR were used to determine
the gross and histological features of the SC which were typically of rodent
features. The mean SC weight and length given as 2.50+/-0.24g and 15.87+/-0.24cm
respectively for the male and 2.32+/-0.16g and 15.40+/-0.61cm for the female
showed no sexual dimorphism. A positive linear relationship between the tail
length and SC weight were found in both sexes (r =0.81 males; r =0.95 females)
suggesting significant contribution of the filum terminale to SC weight. Forty
three internal structures including nuclear aggregations and tracts were traced.
Eight nuclear aggregations of neurons involved in nociception and limb
coordination were observed to be prominent and larger than in laboratory rats.
Same was noted for the dorsal, ventral and lateral funicular tracts which control
the limbic system. This study provides morphometric baseline research information
and delineates the functional aspects of the AGR SC anatomy. The information
provided further strengthens the drive proposing the AGR as an indigenous
research model for regional anaesthesia and locomotor disease.
PMID- 27506168
TI - Anti-Gastric Ulcer Effect of Betulinic Acid in Male Albino Rats.
AB - Betulinic acid (BA) is a lupane-type triterpene that has been identified and
isolated from various plant species used in ethnomedicine in various cultures
across the world. This study was undertaken to elucidate the mechanisms
underlying the anti-ulcer effect of Betulinic acid. The effect of BA on
indomethacin-induced ulcer, gastric mucus secretion, gastric mucus cells count,
basal and histamine-induced gastric acid secretion and levels of malondialdehyde
formation were studied using dose of 0.5, 1.5, and 3.0 mg/kg. The results showed
that BA reduced indomethacin-induced ulceration significantly and significantly
increased gastric mucus secretion in the 1.5 mg/kg and 3.0 mg/kg BA treated rats
compared to the control rats. There was a significant increase in the mucus
cells count in all the treated groups which is in a dose- dependent manner
compared to the control group. There was significant decrease in gastric acid
secretion in each of the BA treated groups compared to the control.
Malondialdehyde concentration significantly decrease in all the treated groups
compared to the control. The anti-gastric ulcer effect of BA may be mediated via
decreasing gastric acid secretion, increasing gastric mucus secretions,
increasing the number of gastric mucus cells and also by reducing the level of
MDA concentration.
PMID- 27506169
TI - Antinociceptive and anti-arthritic properties of hydroethanolic leaf extract of
Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) in Rodents: possible
mechanism of actions.
AB - The leaves of Clausena anisata (Willd.) Hook. f. ex Benth (Rutaceae) is used in
Traditional African medicine for the treatment of various ailments including
arthritis. The present study sought to investigate the antinociceptive and anti
arthritic properties of hydroethanolic leaf extract of Clausena anisata (HeCA).
HeCA (100, 200 or 400 mg/kg, p.o.) was administered 1 h before intraplantar
injection of formalin 1%v/v in saline to evaluate antinociceptive effect.
Moreover, its possible mechanism of antinociceptive action was investigated
through pretreatment of mice with antagonists of receptors implicated in
nociception. Anti!inflammatory effect of the extract was investigated using the
carrageenan-induced paw oedema and complete Freund's adjuvant (CFA)-induced
arthritis models in rats. HeCA (400 mg/kg) treatment significantly reduced the
duration of paw licking/biting during both in the early (42.12%) and late
(75.79%) phases of formalin-induced nociception. However, the antinociceptive
effect elicited by HeCA was reverse by pretreatment of mice with naloxone,
prazosin, yohimbine, ketanserin, L-arginine, and parachlorophenylalanine (PCPA).
HeCA produced dose-dependent and time course decrease in carrageenan-induced paw
oedema. Pre- and post-treatment of rats with HeCA ameliorated CFA-induced
arthritis evidenced in the significant decrease in arthritic index comparatively
similar to the effect of celecoxib. CFA- induced oxidative and nitrosative stress
were attenuated by subchronic treatment with HeCA. Findings from this study shows
that C. anisata possesses antinociceptive activity through possible interaction
with opioidergic, noradrenergic, L-arginine-nitric oxide and serotonergic
pathways as well as anti-arthritic property which could be attributed to its
ability to prevent the release of inflammatory mediators and oxidative stress.
PMID- 27506170
TI - Effects of Oral Maternal Administration of Caffeine on Reproductive Functions of
Male Offspring of Wistar Rats.
AB - Caffeine was investigated for its possible fetal programming effects on
reproductive function of male offspring. Sixty-five pregnant Wistar rats were
grouped into four. Group 1 was control and received distilled water. Groups 2, 3
and 4 were treated orally with 1.14, 3.42 and 5.70 mg/kg body weight of caffeine
respectively. Each group was subdivided into four based on gestation days (GD) 1
7, 8-14, 15-21 and 1-21. The day of parturition was taken as postnatal day zero
(0). Male offspring were sacrificed on postnatal day 70. Parameters determined
were: weight at birth, body weight at postnatal day 21 and 70, anogenital
distance (AGD) index, sperm parameters, reproductive organ weight, histology and
hormonal profile (testosterone, FSH and LH). Data were analyzed using Analysis of
Variance. Level of significance was taken at P<0.05. Male offspring belonging to
caffeine treated dams showed dose dependent significant decreases in birth
weight. Male offspring from dams treated with caffeine during GD 1-7 and GD 1-21
had a significant increase in their AGD index. Also, male offspring from dams
treated with 1.14 and 5.70 mg/kg body weight of caffeine during GD 8-14 had a
significant increase in AGD index. Dams treated with 3.42 mg/kg body weight of
caffeine during GD 15-21, had a significant increase in the AGD index of their
male offspring. The sperm motility of offspring from dams treated with 5.70 mg/kg
body weight of caffeine during GD 1-7 and GD 1-21 were significantly increased.
Offspring of GD 8-14 and GD 15-21 dams treated with 3.42 and 5.70 mg/kg body
weight of caffeine respectively, showed significantly reduced serum testosterone
level. There was a significant decrease in the weight of testes of offspring from
dams treated with caffeine during GD 8-14. Histological sections of testes of
offspring from caffeine treated dams showed interstitial congestions, edema,
reduced germinal epithelial height and detached basal membrane. Maternal caffeine
exposure during different gestational periods adversely affected birth weight and
some reproductive indices in male offspring of Wistar rats.
PMID- 27506171
TI - Effects of Hypothyroidism and Exogenous Thyroxine on Gastrointestinal Organs of
Rat.
AB - Thyroxine (T4) is important in gut development and maturation, and its use in
treating hypothyroidism is becoming more popular. This study was conducted to
evaluate the effect of thyroidectomy and thyroxine replacement on some
gastrointestinal organs. Ten out of 20 thyroidectomised rats received 100pg/kgbw
of T4 for five weeks to become euthyroid while the rest were left to become
hypothyroid. Ten sham operated rats were made hyperthyroid by giving 100pg/kg.bw
of T4 for five weeks, while the other ten sham operated rats served as control.
10mg/kg.bw intraperitoneal injection of ketamine was given as anesthesia for
thyroidectomy and sham operation. At the end of the fifth week, the animals were
sacrificed. Liver, stomach and small intestine were harvested and their
morphological dimensions measured. Everted sacs were made from the small
intestine for glucose transfer studies and slides for histomorphometry. There was
no significant difference in the weights of the liver and stomach of the groups
when compared with the control group. There was significant increase in length
and diameter but reduced wall thickness in the hyperthyroid small intestine;
unlike that of hypothyroid which had significant shorter length, decreased
diameter but increased wall thickness. Villi length and crypt depth was higher in
hyperthyroid but smallest in the hypothyroid. Glucose transfer was lesser in the
hypothyroid but greater in the hyperthyroid intestine. These findings show that
hypothyroidism diminishes the morphological variables of absorption in the small
intestine as a mechanism to reducing its transfer capacity, while thyroxine
replacement increases these variables as mechanism to increasing intestinal
transfer capacity.
PMID- 27506172
TI - Acute Administration of Methionine Affects Performance of Swiss Mice in Learning
and Memory Paradigms.
AB - Methionine, an essential amino acid, plays an essential role in the central
nervous system CNS development. It serves as a crucial intermediate in the
methylation, trans-sulfuration and amino- phosphorylationpathways,necessary for
the synthesis of nucleic acids, phospholipids, hormones, neurotransmitters,
antioxidants, polyamines, catecholamines and other biogenic amines. The effect of
methionine on learning and memory in mice was investigated using Morris water
maze (MWM), Elevated plus maze(EPM) and Y maze (YM). Animals were administered
with distilled water (control), methionine (1,700mg/kg); folate (3mg/kg) or
methionine (1700mg/kg) plus folate (3mg/kg) for 14 days. Escape latency and time
spent in target quadrants; transfer latency and percentage spontaneous
alternations were measured in the MWM, EPM and YM respectively. The animals were
anaesthetized with inhalational chloroform and their brains subsequently
harvested, homogenized and assayed for acetylcholinesterase24 hours after the
experiment.Folate significantly(p<0.05) increased transfer latency (53.33 +/-
12.62) as compared to control (20.1 +/- 5.01) and reduced spontaneous
alternations significantly (25.0 +/- 8.9) when compared to control (44.33 +/-
3.07). When folate was combined with methionine there was also a significant
increase in transfer latency (43.0 +/- 14.39) when compared with control (20.1 +/
5.01). Folate-methionine combination also significantly reduced spontaneous
alternations (20.4 +/- 8.4) as compared to the control (44.33 +/- 3.07) much more
than folate alone. Acetylcholinesterase activities in all groups were not
statistically significant. It can be concluded that acute methionine
administration has some benefits in memory enhancement. However, a short course
folate supplementation impairslearning and working memory especially when
combined with methioninewhich may be as a result of sudden overwhelming of the
methylation cycle, leading to homocysteinemia which is pro-dementia.
PMID- 27506173
TI - Effects of Telfairia Occidentalis Seed Oil on Female Reproductive Functions in
Wistar Rats.
AB - The effects of T. occidentalis seed oil on some female reproductive indices were
investigated in Wistar rats. The study was divided into two phases: (estrous
cycle and pregnancy). Animals were grouped into four: group A received distilled
water (control), groups B, C and D received 400, 600 and 800 mg/kg bw of T.
occidentalis seed oil respectively. The pattern of estrous cycle was determined
for three weeks before and during the treatment. Thereafter, each group was sub-
divided into two. The sub-group-1 rats were mated with male breeders, the litter
size and birth weight of their offsprings was determined. Sub-group-2 rats were
sacrificed and histology of organs and serum levels of LH, FSH and estrogen were
assayed. There was no significant difference between the pre-treatment and post
treatment estrous cycle length. However, there was a significant decrease in the
frequency of diestrus phase during treatment in all the experimental groups when
compared with pre-treatment period but there was no significant difference in the
diestrus phase when compared with the control group. Serum estrogen concentration
was significantly reduced in the group that was treated with 800 mg/kg bw of T.
occidentalis seed oil. Histology of the ovary and uterus in the experimental
groups were similar to that of the control group. Birth weight of pups was
significantly increased in the group treated with 600 mg/kg bw of T. occidentalis
seed oil when compared with the control group. The results of this study suggest
that T. occidentalis seed oil does not alter estrous cycle in Wistar rats.
PMID- 27506174
TI - Safety Evaluation of Osun River Water Containing Heavy Metals and Volatile
Organic Compounds (VOCs) in Rats.
AB - This study evaluated the pH, heavy metals and volatile organic compounds (VOCs)
in Osun river water. It also evaluated its safety in rats. Heavy metals were
determined by atomic absorption spectrophotometry (AAS) while VOCs were
determined by gas chromatography coupled with flame ionization detector (GC-FID).
Male and female rats were exposed to Osun river water for three weeks and then
sacrificed. The abundance of heavy metals in Osun river followed the trend Pb >
Cd > Zn > Fe > Cr > Cu while VOCs followed the trend benzene < ethylbenzene <
toluene < xylene. The concentrations of Pb, Cd and benzene were higher than the
permissible limits of Standards Organization of Nigeria (SON) and World Health
Organization (WHO) respectively. Rats exposed to Osun river water for three weeks
had increased WBC, thiobarbituric acid reactive substances (TBARS), serum
proteins and serum aminotransferases. There were also significant decreases in
HCT, PLT, liver aminotransferases and liver glutathione compared to the control.
These results show that the pollutants in Osun river water are capable of
inducing hematological imbalance and liver cell injury. The toxicity induced in
blood was sex-dependent affecting female rats more than male rats.
PMID- 27506175
TI - Baseline Haematology and Erythrocyte Morphological Changes of Apparently Normal
Dogs Raised in Ibadan, Oyo State.
AB - This study evaluates the haematological parameters and the observed erythrocytes
morphological changesin dogs raised in Ibadan, Oyo State in the south western
part of Nigeria. Blood samples were collected from sixty-four apparently healthy
dogs. The haematological parameters of the blood samples collected were evaluated
with the quantification of the percentage erythrocyte morphological
abnormalities. The result of the quantitative count of the erythrocyte
morphological abnormalities were also converted using reference guide to give the
numerical/descriptive clinical grade of the associated morphological
abnormalities. There was a significant difference between the haematological
parameters reported in this study and the commonly used dog haematological
reference ranges from temperate regions used in laboratories in Nigeria. Some of
the morphological abnormalities observed in this study include echinocyte (4.12+/
0.35%), macrocyte (2.61+/-0.22%) and spherocyte (2.17+/-0.29%) and eccentrocyte
(0.39+/-0.06%) while other such as acanthocyte (1.39+/-0.19), leptocyte (0.71+/
0.13), schizocyte (0.703+/-0.104) and codocyte (0.50+/-0.11) were also seen.
These study findings show that the associated morphological changes were all not
significant and fall within the acceptable range using the reference guide for
erythrocyte morphological abnormalities even when the haematological values
differ significantly fromthe reference value. This study provides baseline
information on the haematological parameters and the novel correlation ofthe
associated erythrocyte abnormalities seen as a corresponding proof of the
apparently healthy status of the dogs raised in Ibadan used for this study. The
study while serving as an important means of verification of the reference range
of haematological parameters also shows that clinical case interpretation using
haematological baseline data from the temperate region should be used with
caution in our tropical environment. This thus necessitates the need for an
advocacy to build a reference range of haematological parameters that can be used
as a working baseline value for the tropical environment.
PMID- 27506176
TI - Salivary Secretion and Composition in Malaria: A Case-control Study.
AB - No previous studies have documented changes in salivary secretion in patients
with malaria. This study aimed to compare salivary secretion and composition in
malaria positive and malaria negative individuals. Ninety participants composed
of 40 malaria parasite positive and 50 malaria parasite negative individuals (age
and gender matched) were included. Malaria diagnosis was achieved by microscopic
examination of Giemsa stained thick and thin film of blood smears. A self
administered questionnaire was used to assess presence or absence of oral
symptoms in the malaria parasite positive individuals. Whole saliva samples were
collected and analyzed for flow rate, pH, total protein and concentrations of
electrolytes (K+, Na+, Ca2+, Cl-, PO42-and HCO32-). Data were analysed using
Independent-Samples t-test and Spearman's correlation test. The salivary flow
rate was significantly reduced in malaria parasite positive individuals (P =
0.001). Oral symptoms were present in 82.5% of the malaria parasite positive
individuals. There was no significant difference in the salivary pH, total
protein and electrolyte ion concentrations between the two groups. Also,
Spearman's correlation test showed no significant relationship between the
presence of oral symptom and the salivary parameters. Salivary flow rates are
reduced in the individuals with malaria. However, presence of oral symptoms in
these individuals may not be attributed to the reduced salivary flow rate.
Further studies are needed to validate our findings and elucidate mechanisms
involved.
PMID- 27506177
TI - A Survey of ABO, Rhesus (D) Antigen and Haemoglobin Genes Variants in Oyo State,
Nigeria.
AB - A survey of ABO and Rhesus (Rh D) antigens and variants of haemoglobin genes
(HbGen) in Oyo state was carried out. This longitudinal study involved the
determination of ABO and Rh(D) antigens in 3241 and HbGen in 2622 male and female
adults (aged 26-65years) respectively using standard methods. 94.5% of the
subjects were Rh(D) positive while 5.5% were Rh(D) negative respectively based on
the detection (Positive) or absence (Negative) of Rh(D) antigen. 22.8% of the
subjects had ABO blood group A, 26.4% were group B, 4.1% were group AB while
46.7% were group O. Further analysis revealed that 695 (21.4%) of the group A
were Apositive while 44 (1.4%) were Anegative. 800 of these subjects (24.7%) were
Bpositive while 56 (1.7%) were group Bnegative. 133 (4.1%) showed group AB out of
which 125 (3.8%) were ABpositive and 8 (0.3%) were ABnegative. 1513 (46.7%) were
group O out of which 1444 (44.6%) were Opositive while 69 (2.1%) were Onegative.
HbGen determination showed that 1933 of the subjects (73.7%) had HbGen AA; 553
(21.1%) were AS; 119 (4.5%) were AC; 11 (0.4%) were SC while 3 subjects
representing 0.1% and 0.2% each had HbGen SS and CC respectively. Although the
results were similar to earlier ones; however, the need for sustained counselling
towards eradication of SS genes and increased research towards identifying
artificial blood substitutes was highlighted in this work. The increasing need
for blood transfusion especially with the increase in various
politically/communally motivated emergency situations underscores this fact.
PMID- 27506178
TI - Effects of Maternal Dexamethasone Exposure During Lactation on Metabolic
Imbalance and Oxidative Stress in the Liver of Male Offsprings of Wistar Rats.
AB - It has been reported in human and animal studies that early exposure to
glucocorticoids could retard growth and subsequent development of cardio
metabolic diseases. Chronic exposure to glucocorticoids induced oxidative stress.
Therefore, the role of oxidative stress in some of the observed metabolic
imbalance needs to be elucidated. This study examined the effects of lactational
dexamethasone exposure on metabolic imbalance and oxidative stress marker in the
liver of male offspring of exposed mother. Twenty lactating dams were divided
into 4 groups of 5 animals each. Group 1 was administered 0.02 ml/100gbwt/day
normal saline through lactation days 1-21. Group 2, 3, and 4 were administered
100 ug/kgbwt/day dexamethasone for lactation days 1-7, 1-14, and 1-21
respectively. The male offspring were thereafter separated and sacrificed at
12weeks of age for evaluation of lipid profile and oxidative stress marker in the
liver. Results from this study indicate that Total Cholesterol (TC),
Triglycerides (TAG) and LDL- cholesterol (LDL-C) were significantly higher in
the Dex 1-7, Dex 1-14 and Dex 1-21 groups when compared with the control. HDL
Cholesterol (HDL-C) was significantly reduced in the Dex 1-7, Dex 1-14 and Dex 1
21 groups relative to the control. Basal Fasting Blood Sugar (FBS) was also
significantly higher in the Dex 1-14 and Dex 1-21 groups when compared with the
control. Liver malondialdehyde was significantly higher in the Dex1-14 and Dex1
21 group compared to the control. However, liver catalase and SOD activity were
all significantly lower in Dex 1-7, Dex 1-14 and Dex 1-21 groups relative to
control. Liver protein was significantly lower in the Dex1-14 and Dex1-21
treatment groups when compared with the control. Findings from this study suggest
that there is possible increase in metabolic imbalance in the offspring of mother
exposed to dexamethasone during lactation and these effects may be secondary to
increase oxidative stress in the liver.
PMID- 27506179
TI - A Novel Annotation Technique During Mapping to Facilitate the Termination of
Atrial Tachycardia Following Ablation for Atrial Fibrillation.
AB - INTRODUCTION: The treatment of atrial tachycardia (AT) occurring after ablation
for atrial fibrillation (AF) is challenging. The most common ablation strategy
relies on entrainment, and electroanatomic activation mapping (EAM) using a
conventional window of interest (WOI), centered on the easily detectable atrial
signal on the coronary sinus catheter. We describe a novel EAM annotation
technique that uses a WOI starting 40 milliseconds prior to the P wave in order
to detect the reentrant AT exit site. This WOI timing is based on the similarity
between scar-related reentrant AT and scar-related ventricular tachycardia.
METHODS: Patients with AT after prior ablation for AF were included. The EAM of
the AT was performed using the novel mapping annotation technique. The ablation
was considered successful if the AT terminated during ablation at the site
identified by this strategy. RESULTS: Twenty-eight patients with 36 ATs were
included. The ATs were classified as follows: mitral annulus (13/36), roof
(11/36), anterior/posterior/lateral left atrial wall (10/36), and RA (2/36). A
complete EAM using the novel annotation technique was achieved in 34 of 36 AT's,
encompassing 94 +/- 6.5% of the cycle length. Low amplitude pre-P fractionated
electrograms were found in 34 of 36 (94%) ATs and these occurred at a mean
distance of 1.8 +/- 1.2 mm from the "early-meets-late" line. Ablation at these
areas resulted in termination of 34 of 36 ATs (94%). CONCLUSION: The novel EAM
annotation allows the accurate detection of the critical isthmus of post-AF
ablation AT. Ablation of these isthmuses results in termination of the AT in the
vast majority of patients.
PMID- 27506180
TI - Ants exhibit asymmetric hybridization in a mosaic hybrid zone.
AB - Research on hybridization between species provides unparalleled insights into the
pre- and postzygotic isolating mechanisms that drive speciation. In social
organisms, colony-level incompatibilities may provide additional reproductive
barriers not present in solitary species, and hybrid zones offer an opportunity
to identify these barriers. Here, we use genotyping-by-sequencing to sequence
hundreds of markers in a hybrid zone between two socially polymorphic ant
species, Formica selysi and Formica cinerea. We characterize the zone, determine
the frequency of hybrid workers, infer whether hybrid queens or males are
produced and investigate whether hybridization is influenced by colony social
organization. We also compare cuticular hydrocarbon profiles and aggression
levels between the two species. The hybrid zone exhibits a mosaic structure. The
asymmetric distribution of hybrids skewed towards F. cinerea suggests a pattern
of unidirectional nuclear gene flow from F. selysi into F. cinerea. The
occurrence of backcrossed individuals indicates that hybrid queens and/or males
are fertile, and the presence of the F. cinerea mitochondrial haplotype in 97% of
hybrids shows that successful F1 hybrids will generally have F. cinerea mothers
and F. selysi fathers. We found no evidence that social organization contributes
to speciation, because hybrids occur in both single-queen and multiple-queen
colonies. Strongly differentiated cuticular hydrocarbon profiles and heightened
interspecific aggression further reveal that species recognition cues are both
present and perceived. The discovery of fertile hybrids and asymmetrical gene
flow is unusual in ants, and this hybrid zone will therefore provide an ideal
system with which to investigate speciation in social insects.
PMID- 27506181
TI - Reference intervals for biochemical and haematological analytes of juvenile
captive-bred long-tailed macaques (Macaca fascicularis) from Mauritius with
examination of the effects of individual characteristics using principal
component analysis.
AB - BACKGROUND: The Mauritian cynomolgus macaque (Macaca fascicularis) is widely used
in biomedical research. Determining reference intervals for biochemical and
haematological analytes provides an important tool for clinical diagnosis and pre
clinical research. METHODS: Blood samples from 736 Mauritian long-tailed macaques
were analysed to determine reference intervals of 13 biochemical and 10
haematological analytes. The need for partitioning the reference interval between
males and females was determined. To examine the variation associated with age,
body weight and sex on the analytes, our correlating, multivariate data set was
first reduced using principal component analysis, and then the effect of these
characteristics on factor scores was examined using GLM analysis. RESULTS:
Partitioning of reference intervals, based on sex, was recommended for albumin,
alkaline phosphatase and mean corpuscular haemoglobin. Sex significantly
influenced the concentration of lymphocytes, granulocytes and white blood cells.
CONCLUSION: These findings provide useful reference data for research involving
Mauritian long-tailed macaques.
PMID- 27506182
TI - Effectiveness and tolerability of simeprevir and sofosbuvir in nontransplant and
post-liver transplant patients with hepatitis C genotype 1.
AB - BACKGROUND: Hepatitis C virus genotype 1a (HCV-1a), prior treatment, cirrhosis
and post-transplant status are historically associated with poor treatment
responses. The new oral direct-acting agents appear to be effective and safe in
these patients. AIMS: To evaluate the effectiveness and tolerability of
simeprevir and sofosbuvir in a diverse real-life cohort of patients, including
difficult-to-treat patients. METHODS: We conducted a retrospective cohort study
in 198 consecutive patients with hepatitis C genotype 1 (148 nontransplant, 50
post transplant), who were treated with simeprevir and sofosbuvir for 12 weeks
between December 2013 and December 2014. Primary outcome was sustained
virological response with undetectable HCV RNA 12 weeks after completion of
therapy (SVR12). Risk factors evaluated for lack of SVR12 included HCV 1a (vs.
1b), prior treatment (vs. none), and cirrhosis (vs. no cirrhosis). RESULTS: SVR12
rates were similar in non- and post-transplant settings, 82% and 88%,
respectively. There were no significant differences in adverse events in patients
regardless of cirrhosis or transplant status. On multivariate analysis also
inclusive of gender and liver transplant status, negative predictors of SVR12
were having at least 2 or 3 risk factors (OR 0.30, 95% CI 0.10-0.87, P = 0.027 or
0.29, 95% CI 0.09-0.85, P = 0.025, respectively). CONCLUSION: Simeprevir and
sofosbuvir combination is a safe and effective regimen for the treatment of non-
and post-transplant patients with traditional risk factors for poor treatment
response, unless more than 2 difficult-to-treat risk factors are present.
PMID- 27506183
TI - Chain conformations and phase behavior of conjugated polymers.
AB - Conjugated polymers may play an important role in various emerging optoelectronic
applications because they combine the chemical versatility of organic molecules
and the flexibility, stretchability and toughness of polymers with semiconducting
properties. Nevertheless, in order to achieve the full potential of conjugated
polymers, a clear description of how their structure, morphology, and macroscopic
properties are interrelated is needed. We propose that the starting point for
understanding conjugated polymers includes understanding chain conformations and
phase behavior. Efforts to predict and measure the persistence length have
significantly refined our intuition of the chain stiffness, and have led to
predictions of nematic-to-isotropic transitions. Exploring mixing between
conjugated polymers and small molecules or other polymers has demonstrated
tremendous advancements in attaining the needed properties for various
optoelectronic devices. Current efforts continue to refine our knowledge of chain
conformations and phase behavior and the factors that influence these properties,
thereby providing opportunities for the development of novel optoelectronic
materials based on conjugated polymers.
PMID- 27506184
TI - Quality of life and national pension receipt after retirement among older adults.
AB - AIM: As the aging population (including baby boomers) retires, its members face
the problem of retirement security. Social security, including the national
pension, is the most important source of retirement security and thus directly
affects the well-being of retired older adults. We investigated the relationship
between national pension receipt and quality of life (QoL) among Koreans aged 60
years or older. METHODS: We used data from the Korean Longitudinal Study of Aging
obtained in 2006-2012 from 340 baseline individuals who had retired. We measured
QoL using a visual analog scale. A generalized estimating equations model was
used to carry out a longitudinal regression analysis on longitudinal data.
RESULTS: When participants who received a national pension were used as the
reference group, those participants who did not receive a national pension had a
QoL of -4.40 (SE = 1.73; P = 0.0109). Additionally, individuals without a
national pension and with a low household income showed the most drastic decrease
in QoL (-10.42; SE = 4.53; P = 0.0214). Individuals without a national pension
and with a low wealth level showed a considerable decrease in QoL compared with
individuals with national pension and with a low wealth level (-8.34; SE = 4.14;
P = 0.0438). CONCLUSIONS: National pension receipt among retired older adults
influences QoL, and the present results suggest that guaranteed income is very
important to retired older adults with a low economic status. Thus, we require
national pension schemes that aim to address retirement security for these
individuals. Geriatr Gerontol Int 2017; 17: 1205-1213.
PMID- 27506185
TI - Surgical treatment of stress urinary incontinence-trans-obturator tape compared
with tension-free vaginal tape-5-year follow up: an economic evaluation.
AB - OBJECTIVE: To conduct an economic evaluation of the use of trans-obturator tape
(TOT) compared with tension-free vaginal tape (TVT) in the surgical treatment of
stress urinary incontinence in women. DESIGN: Cost-utility and cost-effectiveness
analyses from a public-payer perspective, conducted alongside a randomised
clinical trial. SETTING: Health services provided in Alberta, Canada. SAMPLE: A
total of 195 women participated in the randomised clinical trial, followed to 5
years postsurgery. METHODS: Comparisons were undertaken between study groups for
cost and two health-outcome measures. Multiple imputation was used to estimate
the 14% of missing data. Bootstrapping was used to account for sampling
uncertainty. Sensitivity analyses were based on complete case analyses and the
removal of a TVT patient with extreme health service cost. MAIN OUTCOME MEASURES:
The 15D instrument was used to calculate quality-adjusted life-years (QALYs) for
the primary analysis. Absence of serious adverse events was also analysed. Costs
were based on inpatient and outpatient hospital use data and practitioner fee-for
service claims data. RESULTS: The TOT group had a nonsignificant average saving
of $2368 (95% CI -$7166 to $2548) and incremental gain of 0.04 QALYs (95% CI
0.06 to 0.14) compared with TVT. TOT was dominant in over 71% of bootstrap
replications and cost-effective over a wide range of willingness-to-pay. Cost
effectiveness analysis using the absence of an serious adverse events provided
similar results. CONCLUSION: The results suggest that TOT is cost-effective
compared with TVT in the treatment of stress urinary incontinence. TWEETABLE
ABSTRACT: The results of a 5-year cost-effectiveness analysis suggest that trans
obturator tape is cost-effective compared with tension-free vaginal tape in the
treatment of stress urinary incontinence.
PMID- 27506186
TI - Synthesis of substituted benzooxaborinin-1-ols via palladium-catalysed
cyclisation of alkenyl- and alkynyl-boronic acids.
AB - Two new palladium-catalysed reactions have been developed for the synthesis of
stable 4-substituted benzooxaborinin-1-ols. A palladium-catalysed cyclisation of
ortho-alkenylbenzene boronic acids can be used to access 4-chlorobenzooxaborinin
1-ols via a Wacker-type oxidation and chlorination. Alternatively, ortho
alkynylbenzene boronic acids undergo a palladium-catalysed oxyallylation reaction
to provide 4-allylbenzooxaborinin-1-ols.
PMID- 27506187
TI - Size dependence of structural parameters in fcc and hcp Ru nanoparticles,
revealed by Rietveld refinement analysis of high-energy X-ray diffraction data.
AB - To reveal the origin of the CO oxidation activity of Ruthenium nanoparticles (Ru
NPs), we structurally characterized Ru NPs through Rietveld refinement analysis
of high-energy X-ray diffraction data. For hexagonal close-packed (hcp) Ru NPs,
the CO oxidation activity decreased with decreasing domain surface area. However,
for face-centered cubic (fcc) Ru NPs, the CO oxidation activity became stronger
with decreasing domain surface area. In comparing fcc Ru NPs with hcp Ru NPs, we
found that the hcp Ru NPs of approximately 2 nm, which had a smaller domain
surface area and smaller atomic displacement, showed a higher catalytic activity
than that of fcc Ru NPs of the same size. In contrast, fcc Ru NPs larger than 3.5
nm, which had a larger domain surface area, lattice distortion, and larger atomic
displacement, exhibited higher catalytic activity than that of hcp Ru NPs of the
same size. In addition, the fcc Ru NPs had larger atomic displacements than hcp
Ru NPs for diameters ranging from 2.2 to 5.4 nm. Enhancement of the CO oxidation
activity in fcc Ru NPs may be caused by an increase in imperfections due to
lattice distortions of close-packed planes and static atomic displacements.
PMID- 27506188
TI - President's Report.
PMID- 27506189
TI - Discuss the role of microorganisms in the aetiology and pathogenesis of
periapical disease.
AB - The literature indicates that microorganisms have a critical role in the
aetiology and pathogenesis of apical periodontitis. The advancement in
microbiological study methods has allowed for the identification of newer species
associated with the disease process. At our current understanding, however, the
exact roles of specific microorganisms in apical periodontitis are not fully
understood but the poly-microbial aetiology of the disease appears to be
supported by the literature. The endodontic microbiota is comprised of a subset
of microbiota present in the oral cavity, consisting of predominantly anaerobic
bacterial species, some fungal and viral species. The pathogenesis of apical
periodontitis is essentially the result of a complex interplay between bacterial
and host factors, giving rise to a range of presentations depending on the
balance of the interaction. The role of endodontic microbiota in the initiation
and persistence of apical periodontitis means that the mainstay of endodontic
treatment is the elimination of such bacteria. A challenge to the resolution of
apical periodontitis after treatment lies in the inadequacy of treatment protocol
in completely eradicating the pathogenic species and the inherent ability of
certain species to survive the treatment. This issue should be the focus of
future research as we continually search for more predictable treatment methods
of achieving the resolution of apical periodontitis.
PMID- 27506190
TI - Report on the 10th IFEA World Congress, June 03-06, 2016, Cape Town, South
Africa.
PMID- 27506192
TI - ASE (NSW) Report June 2016.
PMID- 27506191
TI - Queensland Newsletter Report May 2016.
PMID- 27506193
TI - Western Australia.
PMID- 27506194
TI - Victoria.
PMID- 27506195
TI - Elucidating tissue specific genes using the Benford distribution.
AB - BACKGROUND: The RNA-seq technique is applied for the investigation of
transcriptional behaviour. The reduction in sequencing costs has led to an
unprecedented trove of gene expression data from diverse biological systems.
Subsequently, principles from other disciplines such as the Benford law, which
can be properly judged only in data-rich systems, can now be examined on this
high-throughput transcriptomic information. The Benford law, states that in many
count-rich datasets the distribution of the first significant digit is not
uniform but rather logarithmic. RESULTS: All tested digital gene expression
datasets showed a Benford-like distribution when observing an entire gene set.
This phenomenon was conserved in development and does not demonstrate tissue
specificity. However, when obedience to the Benford law is calculated for
individual expressed genes across thousands of cells, genes that best and least
adhere to the Benford law are enriched with tissue specific or cell maintenance
descriptors, respectively. Surprisingly, a positive correlation was found between
the obedience a gene exhibits to the Benford law and its expression level,
despite the former being calculated solely according to first digit frequency
while totally ignoring the expression value itself. Nevertheless, genes with low
expression that exhibit Benford behavior demonstrate tissue specific
associations. These observations were extended to predict the likelihood of
tissue specificity based on Benford behaviour in a supervised learning approach.
CONCLUSIONS: These results demonstrate the applicability and potential
predictability of the Benford law for gleaning biological insight from simple
count data.
PMID- 27506196
TI - Prader-Willi syndrome in neonates: twenty cases and review of the literature in
Southern China.
AB - BACKGROUND: Prader-Willi syndrome is a rare genetic abnormality that can be
challenging to diagnose early, but for which early interventions improve
prognosis. METHODS: To improve understanding of Prader-Willi syndrome in neonates
in Asia, we retrospectively analyzed the clinical records of 20 affected newborns
diagnosed in the Department of Neonatology, Guangzhou Women and Children's
Medical Center, Guangzhou, China from January 2007 to December 2014 and performed
a review of the relevant literature. RESULTS: Fourteen boys and six girls
presented with hypotonia, poor responsiveness, feeding difficulty, and
infrequent, weak crying. Different from western patients, the 20 Asian patients
exhibited at least five of the following typical features: prominent forehead,
narrow face, almond-shaped eyes, small mouth, downturned mouth, thin upper lip,
and micromandible. All 14 boys had a small scrotum, including nine with
cryptorchidism. Diagnoses were made with microarray comparative genomic
hybridization. All 20 infants required feeding tubes. Fifteen received swallowing
training immediately after admission; the period of continuous tube feeding for
these patients ranged from 8 to 22 days (mean, 14 +/- 5.3 days). For the five
patients who did not receive swallowing training, the period of continuous tube
feeding ranged from 15 to 35 days (mean, 18 +/- 4.3 days). Comprehensive care
measures included: giving parents detailed health education and basic information
about this disease, teaching skills to promote feeding and prevent suffocation,
increasing children's passive activity, providing nutrition management for normal
development, and preventing excessive or inadequate nutrient intake. CONCLUSIONS:
Neonates with Prader-Willi syndrome in Asia have hypotonia, poor responsiveness,
feeding difficulty, infrequent and weak crying, genital hypoplasia, and
characteristic facial features. Recognition of the syndrome in neonates with
confirmation by genetic testing is essential, because early diagnosis allows
early intervention. Treatment measures including swallowing training can improve
prognosis, prevent growth retardation and obesity, and elevate quality of life in
individuals with Prader-Willi syndrome.
PMID- 27506197
TI - Transcriptomic analysis of the autophagy machinery in crustaceans.
AB - BACKGROUND: The giant freshwater prawn, Macrobrachium rosenbergii, is a decapod
crustacean that is commercially important as a food source. Farming of commercial
crustaceans requires an efficient management strategy because the animals are
easily subjected to stress and diseases during the culture. Autophagy, a stress
response process, is well-documented and conserved in most animals, yet it is
poorly studied in crustaceans. RESULTS: In this study, we have performed an in
silico search for transcripts encoding autophagy-related (Atg) proteins within
various tissue transcriptomes of M. rosenbergii. Basic Local Alignment Search
Tool (BLAST) search using previously known Atg proteins as queries revealed 41
transcripts encoding homologous M. rosenbergii Atg proteins. Among these Atg
proteins, we selected commonly used autophagy markers, including Beclin 1,
vacuolar protein sorting (Vps) 34, microtubule-associated proteins 1A/1B light
chain 3B (MAP1LC3B), p62/sequestosome 1 (SQSTM1), and lysosomal-associated
membrane protein 1 (Lamp-1) for further sequence analyses using comparative
alignment and protein structural prediction. We found that crustacean autophagy
marker proteins contain conserved motifs typical of other animal Atg proteins.
Western blotting using commercial antibodies raised against human Atg marker
proteins indicated their presence in various M. rosenbergii tissues, while
immunohistochemistry localized Atg marker proteins within ovarian tissue,
specifically late stage oocytes. CONCLUSIONS: This study demonstrates that the
molecular components of autophagic process are conserved in crustaceans, which is
comparable to autophagic process in mammals. Furthermore, it provides a
foundation for further studies of autophagy in crustaceans that may lead to more
understanding of the reproduction- and stress-related autophagy, which will
enable the efficient aquaculture practices.
PMID- 27506198
TI - Panx3 links body mass index and tumorigenesis in a genetically heterogeneous
mouse model of carcinogen-induced cancer.
AB - BACKGROUND: Body mass index (BMI) has been implicated as a primary factor
influencing cancer development. However, understanding the relationship between
these two complex traits has been confounded by both environmental and genetic
heterogeneity. METHODS: In order to gain insight into the genetic factors linking
BMI and cancer, we performed chemical carcinogenesis on a genetically
heterogeneous cohort of interspecific backcross mice ((Mus Spretus * FVB/N) F1 *
FVB/N). Using this cohort, we performed quantitative trait loci (QTL) analysis to
identify regions linked to BMI. We then performed an integrated analysis
incorporating gene expression, sequence comparison between strains, and gene
expression network analysis to identify candidate genes influencing both tumor
development and BMI. RESULTS: Analysis of QTL linked to tumorigenesis and BMI
identified several loci associated with both phenotypes. Exploring these loci in
greater detail revealed a novel relationship between the Pannexin 3 gene (Panx3)
and both BMI and tumorigenesis. Panx3 is positively associated with BMI and is
strongly tied to a lipid metabolism gene expression network. Pre-treatment Panx3
gene expression levels in normal skin are associated with tumor susceptibility
and inhibition of Panx function strongly influences inflammation. CONCLUSIONS:
These studies have identified several genetic loci that influence both BMI and
carcinogenesis and implicate Panx3 as a candidate gene that links these
phenotypes through its effects on inflammation and lipid metabolism.
PMID- 27506199
TI - Factors influencing place of delivery for pastoralist women in Kenya: a
qualitative study.
AB - BACKGROUND: Kenya's high maternal mortality ratio can be partly explained by the
low proportion of women delivering in health facilities attended by skilled birth
attendants (SBAs). Many women continue to give birth at home attended by family
members or traditional birth attendants (TBAs). This is particularly true for
pastoralist women in Laikipia and Samburu counties, Kenya. This paper
investigates the socio-demographic factors and cultural beliefs and practices
that influence place of delivery for these pastoralist women. METHODS:
Qualitative data were collected in five group ranches in Laikipia County and
three group ranches in Samburu County. Fifteen in-depth interviews were
conducted: seven with SBAs and eight with key informants. Nineteen focus group
discussions (FGDs) were conducted: four with TBAs; three with community health
workers (CHWs); ten with women who had delivered in the past two years; and two
with husbands of women who had delivered in the past two years. Topics discussed
included reasons for homebirths, access and referrals to health facilities, and
strengths and challenges of TBAs and SBAs. The data were translated, transcribed
and inductively and deductively thematically analysed both manually and using
NVivo. RESULTS: Socio-demographic characteristics and cultural practices and
beliefs influence pastoralist women's place of delivery in Laikipia and Samburu
counties, Kenya. Pastoralist women continue to deliver at home due to a range of
factors including: distance, poor roads, and the difficulty of obtaining and
paying for transport; the perception that the treatment and care offered at
health facilities is disrespectful and unfriendly; lack of education and
awareness regarding the risks of delivering at home; and local cultural values
related to women and birthing. CONCLUSIONS: Understanding factors influencing the
location of delivery helps to explain why many pastoralist women continue to
deliver at home despite health services becoming more accessible. This
information can be used to inform policy and program development aimed at
increasing the proportion of facility-based deliveries in challenging settings.
PMID- 27506201
TI - Isolation and characterization of a novel Rickettsia species (Rickettsia
asembonensis sp. nov.) obtained from cat fleas (Ctenocephalides felis).
AB - A novel rickettsial agent, 'Candidatus Rickettsia asembonensis' strain NMRCiiT,
was isolated from cat fleas, Ctenocephalides felis, from Kenya. Genotypic
characterization of the new isolate based on sequence analysis of five
rickettsial genes, rrs, gltA, ompA, ompB and sca4, indicated that this isolate
clustered with Rickettsia felis URRWXCal2. The degree of nucleotide similarity
demonstrated that isolate NMRCiiT belongs within the genus Rickettsia and fulfils
the criteria for classification as a representative of a novel species. The name
Rickettsia asembonensis sp. nov. is proposed, with NMRCiiT (=DSM 100172T=CDC
CRIRC RAS001T=ATCC VR-1827T) as the type strain.
PMID- 27506202
TI - Guillaine-barre syndrome; a rare complication of melioidosis. a case report.
AB - BACKGROUND: Melioidosis caused by Burkholderia pseudomellei is an infection with
protean clinical manifestations. Guillain-Barre syndrome [GBS] associated with
melioidosis is very rare. CASE PRESENTATION: A 42-year-old woman with diabetes
presented with abdominal pain, vomiting and intermittent fever for one month. Six
months before presentation she had recurrent skin abscesses. Three months before
presentation she had multiple liver abscesses which were aspirated in a local
hospital. The aspirate grew "coliforms" resistant to gentamicin and sensitive to
ceftazidime. On presentation she had high fever and tender hepatomegaly. Ultra
Sound Scan of abdomen showed multiple liver and splenic abscesses. Based on the
suggestive history and sensitivity pattern of the previous growth melioidosis was
suspected and high dose meropenem was started. Antibodies to melioidin were
raised at a titre of 1:10240. The growth from the aspirate of liver abscess was
confirmed as Burkholderia pseudomellei by polymerase chain reaction [PCR]. After
a week of treatment, patient developed bilateral lower limb weakness. Deep tendon
reflexes were absent. There was no sensory loss or bladder/bowel involvement.
Analysis of the cerebro-spinal fluid showed elevated proteins with no cells.
There was severe peripheral neuropathy with axonal degeneration. A diagnosis of
GBS was made and she was treated with plasmapharesis with marked improvement of
neurological deficit. Continuation of intravenous antibiotics lead to further
clinical improvement with normalization of inflammatory markers and resolution of
liver and splenic abscess. Eradication therapy with oral co-trimoxazole and co
amoxyclav was started on the seventh week. Patient was discharged to outpatient
clinic with a plan to continue combination of oral antibiotics for 12 weeks. At
the end of 12 weeks she was well with complete neurological resolution and no
evidence of a relapse. CONCLUSIONS: Guillaine Barre syndrome is a rare
complication of melioidosis and should be suspected in a patient with melioidosis
who develop lower limb weakness. Plasmapharesis can be successfully used to treat
GBS associated with active melioidosis.
PMID- 27506200
TI - A tissue-specific protein purification approach in Caenorhabditis elegans
identifies novel interaction partners of DLG-1/Discs large.
AB - BACKGROUND: Affinity purification followed by mass spectrometry (AP/MS) is a
widely used approach to identify protein interactions and complexes. In
multicellular organisms, the accurate identification of protein complexes by
AP/MS is complicated by the potential heterogeneity of complexes in different
tissues. Here, we present an in vivo biotinylation-based approach for the tissue
specific purification of protein complexes from Caenorhabditis elegans. Tissue
specific biotinylation is achieved by the expression in select tissues of the
bacterial biotin ligase BirA, which biotinylates proteins tagged with the Avi
peptide. RESULTS: We generated N- and C-terminal tags combining GFP with the Avi
peptide sequence, as well as four BirA driver lines expressing BirA ubiquitously
and specifically in the seam and hyp7 epidermal cells, intestine, or neurons. We
validated the ability of our approach to identify bona fide protein interactions
by identifying the known LGL-1 interaction partners PAR-6 and PKC-3. Purification
of the Discs large protein DLG-1 identified several candidate interaction
partners, including the AAA-type ATPase ATAD-3 and the uncharacterized protein
MAPH-1.1. We have identified the domains that mediate the DLG-1/ATAD-3
interaction, and show that this interaction contributes to C. elegans
development. MAPH-1.1 co-purified specifically with DLG-1 purified from neurons,
and shared limited homology with the microtubule-associated protein MAP1A, a
known neuronal interaction partner of mammalian DLG4/PSD95. A CRISPR/Cas9
engineered GFP::MAPH-1.1 fusion was broadly expressed and co-localized with
microtubules. CONCLUSIONS: The method we present here is able to purify protein
complexes from specific tissues. We uncovered a series of DLG-1 interactors, and
conclude that ATAD-3 is a biologically relevant interaction partner of DLG-1.
Finally, we conclude that MAPH-1.1 is a microtubule-associated protein of the
MAP1 family and a candidate neuron-specific interaction partner of DLG-1.
PMID- 27506203
TI - Counteracting learned non-use in chronic stroke patients with reinforcement
induced movement therapy.
AB - BACKGROUND: After stroke, patients who suffer from hemiparesis tend to suppress
the use of the affected extremity, a condition called learned non-use.
Consequently, the lack of training may lead to the progressive deterioration of
motor function. Although Constraint-Induced Movement Therapies (CIMT) have shown
to be effective in treating this condition, the method presents several
limitations, and the high intensity of its protocols severely compromises its
adherence. We propose a novel rehabilitation approach called Reinforcement
Induced Movement Therapy (RIMT), which proposes to restore motor function through
maximizing arm use. This is achieved by exposing the patient to amplified goal
oriented movements in VR that match the intended actions of the patient. We
hypothesize that through this method we can increase the patients self-efficacy,
reverse learned non-use, and induce long-term motor improvements. METHODS: We
conducted a randomized, double-blind, longitudinal clinical study with 18 chronic
stroke patients. Patients performed 30 minutes of daily VR-based training during
six weeks. During training, the experimental group experienced goal-oriented
movement amplification in VR. The control group followed the same training
protocol but without movement amplification. Evaluators blinded to group
designation performed clinical measurements at the beginning, at the end of the
training and at 12-weeks follow-up. We used the Fugl-Meyer Assessment for the
upper extremities (UE-FM) (Sanford et al., Phys Ther 73:447-454, 1993) as a
primary outcome measurement of motor recovery. Secondary outcome measurements
included the Chedoke Arm and Hand Activity Inventory (CAHAI-7) (Barreca et al.,
Arch Phys Med Rehabil 6:1616-1622, 2005) for measuring functional motor gains in
the performance of Activities of Daily Living (ADLs), the Barthel Index (BI) for
the evaluation of the patient's perceived independence (Collin et al., Int
Disabil Stud 10:61-63, 1988), and the Hamilton scale (Knesevich et al., Br J
Psychiatr J Mental Sci 131:49-52, 1977) for the identification of improvements in
mood disorders that could be induced by the reinforcement-based intervention. In
order to study and predict the effects of this intervention we implemented a
computational model of recovery after stroke. RESULTS: While both groups showed
significant motor gains at 6-weeks post-treatment, only the experimental group
continued to exhibit further gains in UE-FM at 12-weeks follow-up (p<.05). This
improvement was accompanied by a significant increase in arm-use during training
in the experimental group. CONCLUSIONS: Implicitly reinforcing arm-use by
augmenting visuomotor feedback as proposed by RIMT seems beneficial for inducing
significant improvement in chronic stroke patients. By challenging the patients'
self-limiting believe system and perceived low self-efficacy this approach might
counteract learned non-use. TRIAL REGISTRATION: Clinical Trials NCT02657070 .
PMID- 27506204
TI - Neuroprotective, Neurotrophic and Anti-oxidative Role of Bacopa monnieri on CUS
Induced Model of Depression in Rat.
AB - Major depression is a life threatening neuropsychiatric disorder that produces
mental illness and major cause of morbidity. The present study was conducted to
evaluate the neuroprotective, neurotrophic and antioxidant potential of Bacopa
monnieri extract (BME) on chronic unpredictable stress (CUS) induced behavioral
depression in rats. Behavioral tests were carried out for investigation of
antidepressant like effects of BME, and potential mechanism was assessed by
determining neurotrophin level and hippocampal neurogenesis. Depressive-like
behavior was assessed by shuttle-box escape test, forced swim test and tail
suspension test. Effect of BME on hypothalamic-pituitary-adrenal (HPA) axis was
evaluated by measuring the plasma level of adrenocorticotropic hormone (ACTH) and
corticosterone. The expression of brain derived neurotrophic factor (BDNF),
neuronal marker doublecortin (DCX) in the hippocampus were measured and
hippocampal neurogenesis was investigated by 5-bromo-2-deoxyuridine/neuronal
nuclei (BrdU/NeuN). In addition, effects of BME on oxidative stress markers were
also measured in the hippocampus of CUS exposed rats. The results indicated that
BME significantly able to attenuate the depressive-like behaviors, normalized the
levels of ACTH, corticosterone, and up-regulate the expression of BDNF, DCX and
BrdU/NeuN in CUS induced rats compared to BME treated rats. It is also found that
BME significantly increased the activity of antioxidant enzymes on CUS induced
rats. These findings revealed that BME exerted neuroprotective effects possibly
by promoting hippocampal neurogenesis with elevation of BDNF level and
antioxidant defense against oxidative stress.
PMID- 27506205
TI - Structural Effects of Solvation by 18-Crown-6 on Gaseous Peptides and TrpCage
after Electrospray Ionization.
AB - Significant effort is being employed to utilize the inherent speed and
sensitivity of mass spectrometry for rapid structural determination of proteins;
however, a thorough understanding of factors influencing the transition from
solution to gas phase is critical for correct interpretation of the results from
such experiments. It was previously shown that combined use of action excitation
energy transfer (EET) and simulated annealing can reveal detailed structural
information about gaseous peptide ions. Herein, we utilize this method to study
microsolvation of charged groups by retention of 18-crown-6 (18C6) in the gas
phase. In the case of GTP (CEGNVRVSRE LAGHTGY), solvation of the 2+ charge state
leads to reduced EET, whereas the opposite result is obtained for the 3+ ion. For
the mini-protein C-Trpcage, solvation by 18C6 leads to dramatic increase in EET
for the 3+ ion. Examination of structural details probed by molecular dynamics
calculations illustrate that solvation by 18C6 alleviates the tendency of charged
side chains to seek intramolecular solvation, potentially preserving native-like
structures in the gas phase. These results suggest that microsolvation may be an
important tool for facilitating examination of native-like protein structures in
gas phase experiments. Graphical Abstract ?.
PMID- 27506206
TI - Native Mass Spectrometry Characterizes the Photosynthetic Reaction Center Complex
from the Purple Bacterium Rhodobacter sphaeroides.
AB - Native mass spectrometry (MS) is an emerging approach to study protein complexes
in their near-native states and to elucidate their stoichiometry and topology.
Here, we report a native MS study of the membrane-embedded reaction center (RC)
protein complex from the purple photosynthetic bacterium Rhodobacter sphaeroides.
The membrane-embedded RC protein complex is stabilized by detergent micelles in
aqueous solution, directly introduced into a mass spectrometer by nano
electrospray (nESI), and freed of detergents and dissociated in the gas phase by
collisional activation. As the collision energy is increased, the chlorophyll
pigments are gradually released from the RC complex, suggesting that native MS
introduces a near-native structure that continues to bind pigments. Two
bacteriochlorophyll a pigments remain tightly bound to the RC protein at the
highest collision energy. The order of pigment release and their resistance to
release by gas-phase activation indicates the strength of pigment interaction in
the RC complex. This investigation sets the stage for future native MS studies of
membrane-embedded photosynthetic pigment-protein and related complexes.Graphical
Abstract.
PMID- 27506207
TI - Characterization of N-Succinylation of L-Lysylphosphatidylglycerol in Bacillus
subtilis Using Tandem Mass Spectrometry.
AB - Phospholipids generally dominate in bacterial lipids. The negatively charged
nature of phospholipids renders bacteria susceptible to cationic antibiotic
peptides. In comparison with Gram-negative bacteria, Gram-positive bacteria in
general have much less zwitterionic phosphatidylethanolamine. However, they are
known for producing aminoacylated phosphatidylglycerol (PG), especially
positively charged L-lysyl-PG, which is catalyzed by lysyl-PG synthase MprF,
which appears to have a broad range of specificity for L-aminoacyl transfer RNAs.
In addition, many Gram-positive bacteria also have a dlt-gene-coded D-alanylation
pathway for lipoteichoic acids and wall teichoic acids covalently attached to a
glycolipid or peptidoglycan. D-Alanylation also masks the dominant negative
charge of the phosphate-rich polymers of teichoic acids. Using mass spectrometry,
we have recently observed that precursor scans in negative mode for deprotonated
amino acid fragments were most sensitive for ester-linked amino acids. Such a
scan for precursors generating an m/z 145 lysyl anion revealed lysyl-PG as well
as an additional species 100 m/z units greater than lysyl-PG. This unexpected
species corresponded precisely to the expected mass of N-succinylated lysyl-PG.
Tandem mass spectrometry revealed a precise match to the fragmentation pattern of
this putative new species. PG, lysyl-PG, and N-succinyl-lysyl-PG may form a
complete loop of charge reversal from -1 to +1 and then back to -1. Analogous
charge reversal by N-succinylation of lysine residues in the bacterial as well as
eukaryotic proteomes has been recently discovered as a major posttranslational
modification. Such modification in bacterial lipids is possibly catalyzed by an
enzyme homologous to the enzymes that modify lysine residues in proteins.
Graphical Abstract ?.
PMID- 27506208
TI - Action-FRET of a Gaseous Protein.
AB - Mass spectrometry is an extremely powerful technique for analysis of biological
molecules, in particular proteins. One aspect that has been contentious is how
much native solution-phase structure is preserved upon transposition to the gas
phase by soft ionization methods such as electrospray ionization. To address this
question-and thus further develop mass spectrometry as a tool for structural
biology-structure-sensitive techniques must be developed to probe the gas-phase
conformations of proteins. Here, we report Forster resonance energy transfer
(FRET) measurements on a ubiquitin mutant using specific photofragmentation as a
reporter of the FRET efficiency. The FRET data is interpreted in the context of
circular dichroism, molecular dynamics simulation, and ion mobility data. Both
the dependence of the FRET efficiency on the charge state-where a systematic
decrease is observed-and on methanol concentration are considered. In the latter
case, a decrease in FRET efficiency with methanol concentration is taken as
evidence that the conformational ensemble of gaseous protein cations retains a
memory of the solution phase conformational ensemble upon electrospray
ionization. Graphical Abstract ?.
PMID- 27506209
TI - Erdheim-Chester disease with bilateral Achilles tendon involvement.
AB - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis with a
broad spectrum of organ manifestations, presenting with characteristic
radiological and histological findings. Soft tissue manifestations
(xanthogranulomas) have been reported to be most commonly found in the region of
the orbits. We report bilateral Achilles tendon xanthogramlomas in a 36-year-old
male with biopsy-proven and B-RAF V600E-positive ECD. Although rare, ECD should
be considered in the differential diagnosis of intratendinous masses.
PMID- 27506210
TI - Anterior Versus Conventional Approach for Resection of Large Right Lobe
Hepatocellular Carcinoma.
AB - PURPOSE: In this study, we aim to report the efficacy of using the anterior
approach (AA) versus the conventional approach (CA), in surgical resection for
large hepatocellular carcinoma (HCC) (>=7 cm) of the right hepatic lobe in terms
of surgical and long-term outcomes. MATERIALS AND METHODS: Between 2000 and 2006,
138 consecutive patients who underwent hepatic resection with curative intent for
large right lobe HCC >=7 cm were identified from a retrospective database. The 40
patients who had AA were compared with the remaining 98 patients who had CA.
Clinicopathological features and surgical results were analyzed and prognostic
factors were evaluated by multivariate analysis. RESULTS: There was no
significant difference between the two groups as regards clinical, laboratory,
and pathological parameters. The operative results had shown a comparable
proportion of patients who experienced massive operative blood loss and
postoperative complications in the two groups. The AA group had a lower
recurrence rate (P = 0.015), better disease-free survival (DFS) (P = 0.001), and
overall survival than the CA group. Our study identified that AA is a prognostic
factor of both overall survival and disease-free survival for large HCC >=7 cm.
CONCLUSION: The AA is a safe and effective technique for right hepatic resection
for large HCC and achieves more advantageous long survival outcome over the CA.
PMID- 27506211
TI - Identification, characterization of selenoprotein W and its mRNA expression
patterns in response to somatostatin 14, cysteamine hydrochloride, 17beta
estradiol and a binary mixture of 17beta-estradiol and cysteamine hydrochloride
in topmouth culter (Erythroculter ilishaeformis).
AB - In this study, a selenoprotein W cDNA was cloned from topmouth culter
(Erythroculter ilishaeformis), and it was designated as EISelW. The EISelW open
reading frame was composed of 261 base pairs (bp), encoding 86-amino-acid
protein. The 5' untranslated region (UTR) consisted of 104 bp, and the 3'-UTR was
composed of 365 bp. A selenocysteine insertion sequence (SECIS) element was found
in the 3'-UTR of EISelW mRNA. The SECIS element was classified as form II because
of a small additional apical loop presented in SECIS element of EISelW mRNA.
Bioinformatic approaches showed that the secondary structure of EISelW was a
beta1-alpha1-beta2-beta3-beta4-alpha2 pattern from amino-terminal to carboxy
terminal. Real-time PCR analysis of EISelW mRNAs expression in 17 tissues showed
that the EISelW mRNA was predominantly expressed in liver, ovary, pituitary,
various regions of the brain, spinal cord and head kidney. Study of
intraperitoneal injection showed that the levels of EISelW mRNA in brain, liver,
ovary and spleen were regulated by somatostatin 14 (SS14), 17beta-estradiol (E2),
cysteamine hydrochloride (CSH) and a binary mixture of E2 and CSH, dependent on
the dosage. These results suggest that E2, SS14 and CSH status may affect tissues
of selenium metabolism by regulating the expression of SelW mRNA, as SelW plays a
central role in selenium metabolism.
PMID- 27506212
TI - Late-onset hypertrophic pyloric stenosis with gastric outlet obstruction: case
report and review of the literature.
AB - We report late-onset hypertrophic pyloric stenosis in a 17-year-old female. She
presented with abdominal pain and an episode of upper gastrointestinal hemorrhage
and subsequently developed gastric outlet obstruction. Work-up revealed
circumferential pyloric thickening, delayed gastric emptying, and a stenotic,
elongated pyloric channel. Biopsies showed benign gastropathy, negative for
Helicobacter pylori, without eosinophilic infiltrates. Botulinum toxin injection
provided limited relief. Diagnostic laparoscopy confirmed the hypertrophic
pylorus and we performed laparoscopic pyloromyotomy. The patient tolerated the
procedure well and had complete symptom resolution at 1-year follow-up.
Hypertrophic pyloric stenosis is a rare cause of gastric outlet obstruction in
adolescents and may be managed successfully with laparoscopic pyloromyotomy.
PMID- 27506213
TI - Do Korean Doctors Think a Palliative Consultation Team Would Be Helpful to Their
Terminal Cancer Patients?
AB - PURPOSE: Hospice and palliative care services (HPC) are not commonly utilized in
Korea; however, palliative care teams (PCTs) have been found to be effective at
addressing the shortcomings in HPC. In this study, we attempted to outline unmet
palliative care needs of terminal cancer patients and the potential benefits of
PCTs as perceived by doctors in Korea. MATERIALS AND METHODS: We surveyed 474
doctors at 10 cancer-related academic conferences from June to November 2014 with
a self-report questionnaire to assess their perceptions of end-of-life care needs
and the expected effects of PCTs on caring for terminal cancer patients. Among
those surveyed, 440 respondents who completed the entire questionnaire were
analyzed. RESULTS: In all domains, fewer participants reported satisfaction with
palliative care services than those reporting needs (p < 0.001). The surveyed
participants also reported difficulties with a shortage of time for treatment,
psychological burden, lack of knowledge regarding hospice care, lengths of stay,
and palliative ward availability. Multivariate logistic regression analysis
revealed that female doctors (odds ratio [OR], 2.672; 95% confidence interval
[CI], 1.035 to 6.892), doctors who agreed that referring my patients to a HPC
means I must give up on my patient (OR, 3.075; 95% CI, 1.324 to 7.127), and
doctors who had no experience with HPC education (OR, 3.337; 95% CI, 1.600 to
7.125) were associated with higher expected effectiveness of PCT activities.
CONCLUSION: The PCT activities were expected to fill the doctor's perceived unmet
HPC needs of terminal cancer patients and difficulties in communications.
PMID- 27506214
TI - Outcome and Prognostic Factors for ETV6/RUNX1 Positive Pediatric Acute
Lymphoblastic Leukemia Treated at a Single Institution in Korea.
AB - PURPOSE: ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most
common genetic subtype of pediatric ALL, has a favorable prognosis. In this
study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our
institution with the aim of identifying significant prognostic variables.
MATERIALS AND METHODS: Sixty-three patients were diagnosed with ETV6/RUNX1 (+)
ALL from 2005 to 2011. Prognostic variables studied included minimal residual
disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of
additional cytogenetic abnormalities. RESULTS: The 5-year event-free survival was
84.1+/-4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis
for a 5-year cumulative incidence of relapse of 15.9+/-4.6%. Multivariate
analysis revealed that the presence MRD, as detected by real-time quantitative
polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1
fusion at end of remission induction, and the presence of additional structural
abnormalities of 12p (translocations or inversions) negatively affected outcome.
Despite treatment such as allogeneic hematopoietic cell transplantation, eight of
the 10 relapsed patients died from disease progression for overall survival of
82.5+/-6.9%. CONCLUSION: ETV6/RUNX1 (+) ALL may be heterogeneous in terms of
prognosis, and variables such as MRD at end ofremission induction or additional
structural abnormalities of 12p could define a subset of patients who are likely
to have poor outcome.
PMID- 27506215
TI - [Coronary interventions : Current developments for improved long-term results].
AB - Based on solid scientific evidence, new generation drug-eluting stents (DES) have
become established as the standard of care in interventional cardiology. With at
least similar safety and superior efficacy over uncoated bare metal stents (BMS)
in various scenarios and including patients with increased bleeding risk, there
are probably no remaining indications favoring the use of BMS. Additional
developments regarding the platform, drug elution characteristics and polymer
design were aimed at optimizing DES with even better outcomes. Although there is
no lack of new variations, none has proven to be superior and several non
inferiority trials lacked statistical power, which precludes the label third
generation (over second generation or new generation DES). While it is recognized
that potential long-term advantages of bioresorbable scaffolds cannot be expected
at this stage from the current ABSORB III trial, the safety and efficacy are
encouraging. Beyond procedural aspects, such as intracoronary imaging, variations
in duration of antiplatelet therapy should help to improve outcomes but still
require careful individual weighting of ischemic vs. bleeding risk.
PMID- 27506216
TI - The roles of tumor- and metastasis-promoting carcinoma-associated fibroblasts in
human carcinomas.
AB - Carcinoma-associated fibroblasts (CAFs) constitute a substantial proportion of
the non-neoplastic mesenchymal cell compartment in various human tumors. These
fibroblasts are phenotypically converted from their progenitors via interactions
with nearby cancer cells during the course of tumor progression. The resulting
CAFs, in turn, support the growth and progression of carcinoma cells. These
fibroblasts have a major influence on the hallmarks of carcinoma and promote
tumor malignancy through the secretion of tumor-promoting growth factors,
cytokines and exosomes, as well as through the remodeling of the extracellular
matrix. Coevolution of CAFs and carcinoma cells during tumorigenesis is therefore
essential for progression into fully malignant tumors. Recent studies have
revealed the molecular mechanisms underlying CAF functions, especially in tumor
invasion, metastasis and drug resistance and have highlighted the significant
heterogeneity among these cells. In this review, we summarize the impacts of
recently identified roles of tumor-promoting CAFs and discuss the therapeutic
implications of targeting the heterotypic interactions of these fibroblasts with
carcinoma cells. Graphical Abstract ?.
PMID- 27506217
TI - Evaluation of the characteristics of leucyl-tRNA synthetase (LeuRS) inhibitor
AN3365 in combination with different antibiotic classes.
AB - Aminoacyl tRNA synthetases are enzymes involved in the key process of coupling an
amino acid to its cognate tRNA. AN3365 is a novel antibiotic that specifically
targets leucyl-tRNA synthetase, whose development was halted after evaluation in
phase II clinical trials owing to the rapid selection of resistance. In an
attempt to bring AN3365 back into the developmental pipeline we have evaluated
the efficacy of AN3365 in combination with different classes of antibiotic and
characterized its mechanism of action. Although we detect no synergy or
antagonism in combination with a range of antibiotic classes, a combination of
AN3365 with colistin reduces the accumulation of AN3365-resistant and colistin
resistance mutations. We also demonstrate that treatment with AN3365 results in
the dramatic accumulation of the alarmone (p)ppGpp, the effector of the stringent
response-a key player in antibiotic tolerance.
PMID- 27506218
TI - Resilience of cassava (Manihot esculenta Crantz) to salinity: implications for
food security in low-lying regions.
AB - Rising sea levels are threatening agricultural production in coastal regions due
to inundation and contamination of groundwater. The development of more salt
tolerant crops is essential. Cassava is an important staple, particularly among
poor subsistence farmers. Its tolerance to drought and elevated temperatures make
it highly suitable for meeting global food demands in the face of climate change,
but its ability to tolerate salt is unknown. Cassava stores nitrogen in the form
of cyanogenic glucosides and can cause cyanide poisoning unless correctly
processed. Previous research demonstrated that cyanide levels are higher in
droughted plants, possibly as a mechanism for increasing resilience to oxidative
stress. We determined the tolerance of cassava to salt at two different stages of
development, and tested the hypothesis that cyanide toxicity would be higher in
salt-stressed plants. Cassava was grown at a range of concentrations of sodium
chloride (NaCl) at two growth stages: tuber initiation and tuber expansion.
Established plants were able to tolerate 100mM NaCl but in younger plants 40mM
was sufficient to retard plant growth severely. Nutrient analysis showed that
plants were only able to exclude sodium at low concentrations. The foliar
cyanogenic glucoside concentration in young plants increased under moderate
salinity stress but was lower in plants grown at high salt. Importantly, there
was no significant change in the cyanogenic glucoside concentration in the
tubers. We propose that the mechanisms for salinity tolerance are age dependent,
and that this can be traced to the relative cost of leaves in young and old
plants.
PMID- 27506219
TI - Pooling-Based Genome-Wide Association Study Identifies Risk Loci in the
Pathogenesis of Ovarian Endometrioma in Chinese Han Women.
AB - Endometriosis, regarded as a complex disease, is influenced by multiple genetic
factors. Recent genome-wide association studies (GWASs) in endometriosis have
identified several susceptibility loci in Caucasian and Japanese populations.
However, the overlapped susceptible loci were few. This case-control study tried
to identify risk loci-related genes for ovarian endometrioma in Chinese Han women
from central China using DNA pooling-based GWAS. Genome DNA samples were
extracted from 3038 participants in central China. Pooling-based genome-wide scan
and individual genotyping were performed using Affymetrix Genome-Wide Human SNP
Array 6.0 and IPLEX Gold system, which demonstrated 10 ovarian endometrioma
related novel risk loci. There were 3 of them with P value < 5 * 10-06,
separately locating in intron of insulin-like growth factor 1 receptor,
chromosome 7 open reading frame 50, and Meis homeobox 1. In conclusion, the
pooling-based GWAS for ovarian endometrioma identified some novel single
nucleotide polymorphisms in Chinese Han women of central China. Further
assessment in other samples will be crucial to confirm the susceptibility of
these results and explore the mechanisms of the related genes in the pathogenesis
of ovarian endometrioma.
PMID- 27506220
TI - Medication, rehabilitation and health care consumption in adults with cerebral
palsy: a population based study.
AB - OBJECTIVE: To evaluate medication, rehabilitation and healthcare consumption in
adults with CP as a function of Gross Motor Function Classification System
(GMFCS) level. DESIGN: Questionnaire-based cross-sectional study. SETTING:
Brittany, a French county. SUBJECTS: Adults with cerebral palsy. INTERVENTIONS:
Questionnaires relating to drugs, orthotic devices, mobility aids, rehabilitation
and medical input were sent to 435 members of a unique regional French network
dedicated to adults with cerebral palsy. The questionnaire was completed by the
participant or a helper if necessary. RESULTS: Of the 282 responders, 7.8% had a
GMFCS level of I, 14.2% II, 17.7% III, 29.1% IV and 31.2% V. Participants
consumed a large amount of healthcare. Almost three-quarters took orally
administered drugs, of which antispastic and antiepileptic drugs were among the
most frequent. Nearly all patients had at least one type of rehabilitation, 87.2%
had physiotherapy, 78% used at least one mobility aid and 69.5% used at least one
orthotic device. The frequency of numerous inputs increased with GMFCS level.
Specificities were found for each GMFCS level, e.g. participants with GMFCS level
IV and V had a high level of medical input and a greater use of trunk-supporting
devices, antireflux and laxative. Profiles could be established based on GMFCS
levels. CONCLUSIONS: Adults with cerebral palsy use a large amount of drugs,
mobility aids, orthotic devices, rehabilitation and medical input. Healthcare is
targeted at cerebral palsy-related issues. GMFCS is a determinant of healthcare
consumption and thus a useful tool for clinical practice to target care
appropriately.
PMID- 27506221
TI - Is the Association Between Sweet and Bitter Perception due to Genetic Variation?
AB - Perceived intensities of sweetness and bitterness are correlated with one another
and each is influenced by genetics. The extent to which these correlations share
common genetic variation, however, remains unclear. In a mainly adolescent sample
(n = 1901, mean age 16.2 years), including 243 monozygotic (MZ) and 452 dizygotic
(DZ) twin pairs, we estimated the covariance among the perceived intensities of 4
bitter compounds (6-n-propylthiouracil [PROP], sucrose octa-acetate, quinine,
caffeine) and 4 sweeteners (the weighted mean ratings of glucose, fructose,
neohesperidine dihydrochalcone, aspartame) with multivariate genetic modeling.
The sweetness factor was moderately correlated with sucrose octa-acetate,
quinine, and caffeine (rp = 0.35-0.40). This was mainly due to a shared genetic
factor (rg = 0.46-0.51) that accounted for 17-37% of the variance in the 3 bitter
compounds' ratings and 8% of the variance in general sweetness ratings. In
contrast, an association between sweetness and PROP only became evident after
adjusting for the TAS2R38 diplotype (rp increased from 0.18 to 0.32) with the
PROP genetic factor accounting for 6% of variance in sweetness. These genetic
associations were not inflated by scale use bias, as the cross-trait correlations
for both MZ and DZ twins were weak. There was also little evidence for mediation
by cognition or behavioral factors. This suggests an overlap of genetic variance
between perceptions of sweetness and bitterness from a variety of stimuli, which
includes PROP when considering the TAS2R38 diplotype. The most likely sources of
shared variation are within genes encoding post-receptor transduction mechanisms
common to the various taste G protein-coupled receptors.
PMID- 27506222
TI - Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes:
The ADJUNCT ONE Treat-To-Target Randomized Trial.
AB - OBJECTIVE: To investigate whether liraglutide added to treat-to-target insulin
improves glycemic control and reduces insulin requirements and body weight in
subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS: A 52-week, double
blind, treat-to-target trial involving 1,398 adults randomized 3:1 to receive
once-daily subcutaneous injections of liraglutide (1.8, 1.2, or 0.6 mg) or
placebo added to insulin. RESULTS: HbA1c level was reduced 0.34-0.54% (3.7-5.9
mmol/mol) from a mean baseline of 8.2% (66 mmol/mol), and significantly more for
liraglutide 1.8 and 1.2 mg compared with placebo (estimated treatment differences
[ETDs]: 1.8 mg liraglutide -0.20% [95% CI -0.32; -0.07]; 1.2 mg liraglutide
0.15% [95% CI -0.27; -0.03]; 0.6 mg liraglutide -0.09% [95% CI -0.21; 0.03]).
Insulin doses were reduced by the addition of liraglutide 1.8 and 1.2 mg versus
placebo (estimated treatment ratios: 1.8 mg liraglutide 0.92 [95% CI 0.88; 0.96];
1.2 mg liraglutide 0.95 [95% CI 0.91; 0.99]; 0.6 mg liraglutide 1.00 [95% CI
0.96; 1.04]). Mean body weight was significantly reduced in all liraglutide
groups compared with placebo ETDs (1.8 mg liraglutide -4.9 kg [95% CI -5.7;
4.2]; 1.2 mg liraglutide -3.6 kg [95% CI -4.3; -2.8]; 0.6 mg liraglutide -2.2 kg
[95% CI -2.9; -1.5]). The rate of symptomatic hypoglycemia increased in all
liraglutide groups (estimated rate ratios: 1.8 mg liraglutide 1.31 [95% CI 1.07;
1.59]; 1.2 mg liraglutide 1.27 [95% CI 1.03; 1.55]; 0.6 mg liraglutide 1.17 [95%
CI 0.97; 1.43]), and hyperglycemia with ketosis increased significantly for
liraglutide 1.8 mg only (event rate ratio 2.22 [95% CI 1.13; 4.34]). CONCLUSIONS:
Liraglutide added to insulin therapy reduced HbA1c levels, total insulin dose,
and body weight in a population that was generally representative of subjects
with type 1 diabetes, accompanied by increased rates of symptomatic hypoglycemia
and hyperglycemia with ketosis, thereby limiting clinical use in this group.
PMID- 27506223
TI - A Smartphone Application to Deliver a Treat-to-Target Insulin Titration Algorithm
in Insulin-Naive Patients With Type 2 Diabetes: A Pilot Randomized Controlled
Trial.
PMID- 27506224
TI - Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats
From Gestation Day 6 Through Postnatal Day 90.
PMID- 27506225
TI - Alternatives to HIST for acellular pertussis vaccines: progress and challenges in
replacement.
AB - The 'International Workshop on Alternatives to the Murine Histamine Sensitization
Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement
of HIST' was held on 24 August 2014, in Prague, Czech Republic, as a satellite
meeting to the 9th World Congress on Alternatives and Animal Use in the Life
Sciences. Participants discussed the progress and challenges associated with the
development, validation, and implementation of in vitro assays as replacements
for the histamine sensitisation test (HIST) for acellular pertussis vaccines.
Discussions focused on the consistency approach, the necessary framework for
regulatory acceptance of a harmonised method, and recent international efforts
towards the development of in vitro assays to replace the HIST. Workshop
participants agreed that acceptable alternatives to the HIST should be based on
ADP ribosylation-mediated cell intoxication and therefore that the CHO cell
clustering assay, which measures cell intoxication, should be further pursued and
developed as a possible replacement for the HIST. Participants also agreed to
continue ongoing multinational discussions involving national and international
standardisation authorities to reach consensus and to organise collaborative
studies in this context for assay characterisation and calibration of reference
materials.
PMID- 27506226
TI - DTMiner: identification of potential disease targets through biomedical
literature mining.
AB - MOTIVATION: Biomedical researchers often search through massive catalogues of
literature to look for potential relationships between genes and diseases. Given
the rapid growth of biomedical literature, automatic relation extraction, a
crucial technology in biomedical literature mining, has shown great potential to
support research of gene-related diseases. Existing work in this field has
produced datasets that are limited both in scale and accuracy. RESULTS: In this
study, we propose a reliable and efficient framework that takes large biomedical
literature repositories as inputs, identifies credible relationships between
diseases and genes, and presents possible genes related to a given disease and
possible diseases related to a given gene. The framework incorporates name entity
recognition (NER), which identifies occurrences of genes and diseases in texts,
association detection whereby we extract and evaluate features from gene-disease
pairs, and ranking algorithms that estimate how closely the pairs are related.
The F1-score of the NER phase is 0.87, which is higher than existing studies. The
association detection phase takes drastically less time than previous work while
maintaining a comparable F1-score of 0.86. The end-to-end result achieves a 0.259
F1-score for the top 50 genes associated with a disease, which performs better
than previous work. In addition, we released a web service for public use of the
dataset. AVAILABILITY AND IMPLEMENTATION: The implementation of the proposed
algorithms is publicly available at http://gdr
web.rwebox.com/public_html/index.php?page=download.php The web service is
available at http://gdr-web.rwebox.com/public_html/index.php CONTACT:
jenny.wei@astrazeneca.com or kzhu@cs.sjtu.edu.cn Supplementary information:
Supplementary data are available at Bioinformatics online.
PMID- 27506227
TI - Support vector machine model of developmental brain gene expression data for
prioritization of Autism risk gene candidates.
AB - MOTIVATION: Autism spectrum disorders (ASD) are a group of neurodevelopmental
disorders with clinical heterogeneity and a substantial polygenic component. High
throughput methods for ASD risk gene identification produce numerous candidate
genes that are time-consuming and expensive to validate. Prioritization methods
can identify high-confidence candidates. Previous ASD gene prioritization methods
have focused on a priori knowledge, which excludes genes with little functional
annotation or no protein product such as long non-coding RNAs (lncRNAs). RESULTS:
We have developed a support vector machine (SVM) model, trained using brain
developmental gene expression data, for the classification and prioritization of
ASD risk genes. The selected feature model had a mean accuracy of 76.7%, mean
specificity of 77.2% and mean sensitivity of 74.4%. Gene lists comprised of an
ASD risk gene and adjacent genes were ranked using the model's decision function
output. The known ASD risk genes were ranked on average in the 77.4th, 78.4th and
80.7th percentile for sets of 101, 201 and 401 genes respectively. Of 10,840
lncRNA genes, 63 were classified as ASD-associated candidates with a confidence
greater than 0.95. Genes previously associated with brain development and
neurodevelopmental disorders were prioritized highly within the lncRNA gene list.
CONTACT: liangjw@clemson.eduSupplementary information: Supplementary data are
available at Bioinformatics online.
PMID- 27506229
TI - Skills for Healthy Adult Relationships at the University of Maryland, Baltimore
County: Program Development and Preliminary Data.
AB - The present study examines the development and preliminary pilot findings of
Skills for Healthy Adult Relationships at the University of Maryland, Baltimore
County (SHARe@UMBC)-an intimate partner violence prevention program for college
students. SHARe@UMBC is based on an integrative cognitive-behavioral model of
communication and emotion regulation in close interpersonal relationships. There
were four aims of the present study: first, to describe program development;
second, to examine program acceptability and participant satisfaction; third, to
examine the extent to which participants acquired relationship skills and their
level of confidence in using those skills; and fourth, to examine perpetration
and victimization of physical, sexual, and psychological aggression. These aims
utilized data collected before program initiation, immediately after program
completion, and at a follow-up 9 to 15 months after program completion. Findings
from two pilot groups (15 students in total; eight women and seven men) indicated
high ratings of program acceptability and satisfaction, reductions in negative
communication, improvements in confidence using conflict management strategies
with romantic partners and peers, and confidence initiating new romantic
relationships. In addition, large effect sizes were observed for confidence
providing emotional support to a romantic partner and self-disclosure with peers.
Participants reported no incidents of physical, sexual, or psychological
aggression perpetration or victimization at follow-up. Pilot implementation and
initial uncontrolled results are encouraging and provide support for initiating a
more extensive controlled investigation of program efficacy.
PMID- 27506228
TI - Acute Precipitants of Physical Elder Abuse: Qualitative Analysis of Legal Records
From Highly Adjudicated Cases.
AB - Elder abuse is a common phenomenon with potentially devastating consequences for
older adults. Although researchers have begun to identify predisposing risk
factors for elder abuse victims and abusers, little is known about the acute
precipitants that lead to escalation to physical violence. We analyzed legal
records from highly adjudicated cases to describe these acute precipitants for
physical elder abuse. In collaboration with a large, urban district attorney's
office, we qualitatively evaluated legal records from 87 successfully prosecuted
physical elder abuse cases from 2003 to 2015. We transcribed and analyzed
narratives of the events surrounding physical abuse within victim statements,
police reports, and prosecutor records. We identified major themes using content
analysis. We identified 10 categories of acute precipitants that commonly
triggered physical elder abuse, including victim attempting to prevent the abuser
from entering or demanding that he or she leave, victim threatening or attempting
to leave/escape, threat or perception that the victim would involve the
authorities, conflict about a romantic relationship, presence during/intervention
in ongoing family violence, issues in multi-generational child rearing, conflict
about the abuser's substance abuse, confrontation about financial exploitation,
dispute over theft/destruction of property, and disputes over minor household
issues. Common acute precipitants of physical elder abuse may be identified.
Improved understanding of these acute precipitants for escalation to physical
violence and their contribution to elder abuse may assist in the development of
prevention and management strategies.
PMID- 27506230
TI - Implementing a Systematic Screening Procedure for Older Adult Mistreatment Within
Individual Clinical Supervision: Is It Feasible?
AB - Home care professionals are well positioned to witness or prevent older adult
mistreatment in the community. Screening efforts are important because most
victims will not easily come forth. Two Canadian local community service centers
implemented a systematic screening procedure within preexisting individual
clinical supervision sessions to support social workers and improve detection of
mistreatment. The aim of this pilot project was to assess fidelity,
acceptability, and feasibility of the new procedure. Qualitative data was
collected using individual interviews with two clinical supervisors, one focus
group with eight social workers and content transcribed from 15 supervision
sessions. It was estimated that 400 clients were screened for older adult
mistreatment using this new procedure. Results showed the procedure was judged
acceptable because it sensitized social workers to risk factors, gave them time
to reflect upon and discuss probable cases with their clinical supervisor.
Nonetheless, participants did not use the designated statistical code in the new
procedure to document mistreatment situations. Feasibility was mainly challenged
by the fact that screening for older adult mistreatment competes with other
organizational priorities. Future initiatives must develop strategies to
counteract those barriers.
PMID- 27506231
TI - Microbial Activation of Bacillus subtilis-Immobilized Microgel Particles for
Enhanced Oil Recovery.
AB - Microbially enhanced oil recovery involves the use of microorganisms to extract
oil remaining in reservoirs. Here, we report fabrication of microgel particles
with immobilized Bacillus subtilis for application to microbially enhanced oil
recovery. Using B. subtilis isolated from oil-contaminated soils in Myanmar, we
evaluated the ability of this microbe to reduce the interfacial tension at the
oil-water interface via production of biosurfactant molecules, eventually
yielding excellent emulsification across a broad range of the medium pH and ionic
strength. To safely deliver B. subtilis into a permeable porous medium, in this
study, these bacteria were physically immobilized in a hydrogel mesh of microgel
particles. In a core flooding experiment, in which the microgel particles were
injected into a column packed with silica beads, we found that these particles
significantly increased oil recovery in a concentration-dependent manner. This
result shows that a mesh of microgel particles encapsulating biosurfactant
producing microorganisms holds promise for recovery of oil from porous media.
PMID- 27506232
TI - Differentiation of pulmonary bacterial pathogens in cystic fibrosis by volatile
metabolites emitted by their in vitro cultures: Pseudomonas aeruginosa,
Staphylococcus aureus, Stenotrophomonas maltophilia and the Burkholderia cepacia
complex.
AB - As a contribution to the continuing search for breath biomarkers of lung and
airways infection in patients with cystic fibrosis, CF, we have analysed the
volatile metabolites released in vitro by Pseudomonas aeruginosa and other
bacteria involved in respiratory infections in these patients, i.e. those
belonging to the Burkholderia cepacia complex, Staphylococcus aureus or
Stenotrophomonas maltophilia. These opportunistic pathogens are generally
harmless to healthy people but they may cause serious infections in patients with
severe underlying disease or impaired immunity such as CF patients. Volatile
organic compounds emitted from the cultures of strains belonging to the above
mentioned four taxa were analysed by selected ion flow tube mass spectrometry. In
order to minimize the effect of differences in media composition all strains were
cultured in three different liquid media. Multivariate statistical analysis
reveals that the four taxa can be well discriminated by the differences in the
headspace VOC concentration profiles. The compounds that should be targeted in
breath as potential biomarkers of airway infection were identified for each of
these taxa of CF pathogens.
PMID- 27506233
TI - Single Figure Publications: Towards a novel alternative format for scholarly
communication.
AB - The single figure publication is a novel, efficient format by which to
communicate scholarly advances. It will serve as a forerunner of the nano
publication, a modular unit of information critical for machine-driven data
aggregation and knowledge integration.
PMID- 27506234
TI - Changes in Functional Connectivity of Default Mode Network with Auditory and
Right Frontoparietal Networks in Poststroke Aphasia.
AB - To evaluate the influence of poststroke aphasia on the functional association of
widespread large-scale neuronal networks, we analyzed functional connectivity
(FC) between resting-state brain networks (RSNs) in aphasic patients (N = 15) and
in healthy volunteers (N = 17) of the same age using resting-state functional
connectivity magnetic resonance imaging. As a result, six RSNs were isolated and
cross-correlation matrices were computed for their time courses. Aphasic patients
showed decreased correlations between posterior part of the default mode (pDMN)
and both auditory (AUD) and right frontoparietal (RFP) networks. Additionally, we
calculated regions of interest-based FC (ROI-FC), gray and white matter volumes
in the ROIs overlapping with pDMN, AUD, and RFP. ROI-FC analysis showed decreased
FC between the right pars triangularis and both right middle frontal and right
superior frontal gyri. The decreased pDMN-RFP connectivity in patients is likely
to reflect changes in FC of these nodes. The lesion in the regions overlapping
with pDMN and AUD networks leads to the significantly decreased pDMN-AUD
connectivity. Our results suggest that abnormal FC in stroke patients may reflect
the impairment of activity not only in the regions directly affected by stroke
lesion in the left hemisphere but also in the homotopic regions of the intact
right hemisphere. The increase of gray and white matter volume in the right
supramarginal gyrus, the functional hub of pDMN, AUD, and RFP networks,
correlated with less speech impairment. This increase might reflect a right
hemisphere neuroplasticity process to compensate the impaired function of the
homotopic region of left frontoparietal network (LFP), pDMN, and AUD in the left
hemisphere. The presented results contribute to the hypothesized compensative
role of the transfer of attention and executive functions from the damaged areas
in the left hemisphere to the right homotopic areas, accompanied by more
preserved language skills at the chronic stroke stage.
PMID- 27506236
TI - Relative and Absolute Reliabilities of the Conners' Continuous Performance Test
II in Schizophrenia.
AB - OBJECTIVE: The Conners' Continuous Performance Test II (CCPT-II) is one of the
most commonly used tests of sustained attention in schizophrenia. To manage and
monitor sustained attention deficits in schizophrenia, clinicians have to
reliably assess the degree of attention impairment. The purpose of our study was
to determine the relative and absolute reliability of the CCPT-II in
schizophrenia. METHOD: The final sample was a total of 108 patients with
schizophrenia. The primary measures in this study were the CCPT-II and the
Clinical Global Impression-Severity (CGI-S). The CCPT-II was administered twice,
1 month apart, by a specially trained occupational therapist. We assessed two
types of reliability: relative and absolute reliability. Relative reliability was
determined with the intra-class correlation coefficient (ICC). Absolute
reliability was quantified with standard error of measurement (SEM), minimal
detectable change (MDC), and Bland-Altman's 95% limits of agreement (LOA).
RESULTS: The ICCs for the five CCPT-II indexes (Omissions, Commissions, Hit RT,
Hit RT Std Error, and Variability) ranged from 0.66 to 0.79. The MDCs (MDC%) of
the five indices were 13.53 (156.78), 10.67 (47.85), 122.10 (34.16), 8.15
(106.82), and 25.81 (162.63), respectively. CONCLUSIONS: According to the
results, the CCPT-II has limited reliability in monitoring the sustained
attention function of patients with schizophrenia. Our results can be used as a
reference for the measurement error of CCPT-II to help clinicians and researchers
determine the true change between successive assessments of patients with
schizophrenia.
PMID- 27506235
TI - Conceptual Models and Guidelines for Clinical Assessment of Financial Capacity.
AB - The ability to manage financial affairs is a life skill of critical importance,
and neuropsychologists are increasingly asked to assess financial capacity across
a variety of settings. Sound clinical assessment of financial capacity requires
knowledge and appreciation of applicable clinical conceptual models and
principles. However, the literature has presented relatively little conceptual
guidance for clinicians concerning financial capacity and its assessment. This
article seeks to address this gap. The article presents six clinical models of
financial capacity : (1) the early gerontological IADL model of Lawton, (2) the
clinical skills model and (3) related cognitive psychological model developed by
Marson and colleagues, (4) a financial decision-making model adapting earlier
decisional capacity work of Appelbaum and Grisso, (5) a person-centered model of
financial decision-making developed by Lichtenberg and colleagues, and (6) a
recent model of financial capacity in the real world developed through the
Institute of Medicine. Accompanying presentation of the models is discussion of
conceptual and practical perspectives they represent for clinician assessment.
Based on the models, the article concludes by presenting a series of conceptually
oriented guidelines for clinical assessment of financial capacity. In summary,
sound assessment of financial capacity requires knowledge and appreciation of
clinical conceptual models and principles. Awareness of such models, principles
and guidelines will strengthen and advance clinical assessment of financial
capacity.
PMID- 27506237
TI - The Wayfinding Questionnaire as a Self-report Screening Instrument for Navigation
related Complaints After Stroke: Internal Validity in Healthy Respondents and
Chronic Mild Stroke Patients.
AB - OBJECTIVE: In current stroke care, cognitive problems are usually diagnosed in a
stepwise manner. More specifically, screening instruments are first applied to
support healthcare professionals in deciding whether a second step (an extensive
assessment) would be appropriate. None of the existing screening instruments,
however, takes navigation ability into account. This is problematic, as
navigation impairment after stroke has been shown to be common, more so than
previously thought. The Wayfinding Questionnaire (WQ) is therefore presented as a
screening instrument for navigation-related complaints after stroke. The internal
validity of the WQ was investigated in two samples of participants to establish
the final version. METHOD AND RESULTS: In Study 1, the WQ was administered in a
representative sample of 356 healthy participants. Its factor structure was
investigated using a principal component analysis. This procedure resulted in
deletion of four items and revealed a three-factor structure: "Navigation and
Orientation," "Spatial Anxiety," and "Distance Estimation". In Study 2, a
confirmatory analysis was performed to directly verify the factor structure as
obtained in Study 1 based on data of 158 chronic mild stroke patients. Fit
indices of the confirmatory analysis indicated acceptable model fit. The
reliability of the three subscales was found to be very good in both healthy
participants and patients. CONCLUSIONS: These studies allowed us to determine the
final version of the WQ. The results indicated that the WQ is an internally valid
and reliable instrument that can be interpreted using a three-factor structure in
both healthy respondents and chronic mild stroke patients.
PMID- 27506238
TI - The Allelochemical MDCA Inhibits Lignification and Affects Auxin Homeostasis.
AB - The phenylpropanoid 3,4-(methylenedioxy)cinnamic acid (MDCA) is a plant-derived
compound first extracted from roots of Asparagus officinalis and further
characterized as an allelochemical. Later on, MDCA was identified as an efficient
inhibitor of 4-COUMARATE-CoA LIGASE (4CL), a key enzyme of the general
phenylpropanoid pathway. By blocking 4CL, MDCA affects the biosynthesis of many
important metabolites, which might explain its phytotoxicity. To decipher the
molecular basis of the allelochemical activity of MDCA, we evaluated the effect
of this compound on Arabidopsis thaliana seedlings. Metabolic profiling revealed
that MDCA is converted in planta into piperonylic acid (PA), an inhibitor of
CINNAMATE-4-HYDROXYLASE (C4H), the enzyme directly upstream of 4CL. The
inhibition of C4H was also reflected in the phenolic profile of MDCA-treated
plants. Treatment of in vitro grown plants resulted in an inhibition of primary
root growth and a proliferation of lateral and adventitious roots. These observed
growth defects were not the consequence of lignin perturbation, but rather the
result of disturbing auxin homeostasis. Based on DII-VENUS quantification and
direct measurement of cellular auxin transport, we concluded that MDCA disturbs
auxin gradients by interfering with auxin efflux. In addition, mass spectrometry
was used to show that MDCA triggers auxin biosynthesis, conjugation, and
catabolism. A similar shift in auxin homeostasis was found in the c4h mutant ref3
2, indicating that MDCA triggers a cross talk between the phenylpropanoid and
auxin biosynthetic pathways independent from the observed auxin efflux
inhibition. Altogether, our data provide, to our knowledge, a novel molecular
explanation for the phytotoxic properties of MDCA.
PMID- 27506239
TI - Effects of Auxins on PIN-FORMED2 (PIN2) Dynamics Are Not Mediated by Inhibiting
PIN2 Endocytosis.
AB - By using the photoconvertible fluorescence protein Dendra2 as a tag we
demonstrated that neither the naturally occurring auxins indole-3-acetic acid and
indole-3-butyric acid, nor the synthetic auxin analogs 1-naphthaleneacetic acid
and 2,4-dichlorophenoxyacetic acid nor compounds inhibiting polar auxin transport
such as 2,3,5-triiodobenzoic acid and 1-N-naphthylphthalamic acid, were able to
inhibit endocytosis of the putative auxin transporter PIN-FORMED2 (PIN2) in
Arabidopsis (Arabidopsis thaliana) root epidermis cells. All compounds, except
Indole-3-butyric acid, repressed the recovery of the PIN2-Dendra2 plasma membrane
pool after photoconversion when they were used in high concentrations. The
synthetic auxin analogs 1-naphthaleneacetic acid and 2,4-dichlorophenoxyacetic
acid showed the strongest inhibition. Auxins and auxin transport inhibitors
suppressed also the accumulation of both newly synthesized and endocytotic PIN2
pools in Brefeldin A compartments (BFACs). Furthermore, we demonstrated that all
compounds are also interfering with BFAC formation. The synthetic auxin analogs
caused the highest reduction in the number and size of BFACs. We concluded that
auxins and inhibitors of auxin transport do affect PIN2 turnover in the cells,
but it is through the synthetic rather than the endocytotic pathway. The study
also confirmed inappropriateness of the BFA-based approach to study PIN2
endocytosis because the majority of PIN2 accumulating in BFACs is newly
synthesized and not derived from the plasma membrane.
PMID- 27506240
TI - The DEK1 Calpain Linker Functions in Three-Dimensional Body Patterning in
Physcomitrella patens.
AB - The DEFECTIVE KERNEL1 (DEK1) calpain is a conserved 240-kD key regulator of three
dimensional body patterning in land plants acting via mitotic cell plane
positioning. The activity of the cytosolic C-terminal calpain protease is
regulated by the membrane-anchored DEK1 MEM, which is connected to the calpain
via the 600-amino acid residue Linker. Similar to the calpain and MEM domains,
the Linker is highly conserved in the land plant lineage, the similarity dropping
sharply compared with orthologous charophyte sequences. Using site-directed
mutagenesis, we studied the effect on Physcomitrella patens development by
deleting the Linker and two conserved Linker motifs. The results show that
removal of the Linker has nearly the same effect as removal of the entire DEK1
gene. In contrast, deletion of the conserved Laminin_G3 (LG3) domain had a milder
effect, perturbing leafy gametophore patterning and archegonia development. The
LG3 domain from Marchantia polymorpha is fully functional in P. patens, whereas
angiosperm sequences are not functional. Deletion of a C-terminal Linker
subsegment containing a potential calpain autolytic site severely disturbs
gametophore development. Finally, changing one of the three calpain active-site
amino acid residues results in the same phenotype as deleting the entire DEK1
gene. Based on the conserved nature of animal and DEK1 calpains, we propose that
the DEK1 MEM-Linker complex inactivates the calpain by forcing apart the two
calpain subunits carrying the three amino acids of the active site.
PMID- 27506241
TI - ORM Expression Alters Sphingolipid Homeostasis and Differentially Affects
Ceramide Synthase Activity.
AB - Sphingolipid synthesis is tightly regulated in eukaryotes. This regulation in
plants ensures sufficient sphingolipids to support growth while limiting the
accumulation of sphingolipid metabolites that induce programmed cell death.
Serine palmitoyltransferase (SPT) catalyzes the first step in sphingolipid
biosynthesis and is considered the primary sphingolipid homeostatic regulatory
point. In this report, Arabidopsis (Arabidopsis thaliana) putative SPT regulatory
proteins, orosomucoid-like proteins AtORM1 and AtORM2, were found to interact
physically with Arabidopsis SPT and to suppress SPT activity when coexpressed
with Arabidopsis SPT subunits long-chain base1 (LCB1) and LCB2 and the small
subunit of SPT in a yeast (Saccharomyces cerevisiae) SPT-deficient mutant.
Consistent with a role in SPT suppression, AtORM1 and AtORM2 overexpression lines
displayed increased resistance to the programmed cell death-inducing mycotoxin
fumonisin B1, with an accompanying reduced accumulation of LCBs and C16 fatty
acid-containing ceramides relative to wild-type plants. Conversely, RNA
interference (RNAi) suppression lines of AtORM1 and AtORM2 displayed increased
sensitivity to fumonisin B1 and an accompanying strong increase in LCBs and C16
fatty acid-containing ceramides relative to wild-type plants. Overexpression
lines also were found to have reduced activity of the class I ceramide synthase
that uses C16 fatty acid acyl-coenzyme A and dihydroxy LCB substrates but
increased activity of class II ceramide synthases that use very-long-chain fatty
acyl-coenzyme A and trihydroxy LCB substrates. RNAi suppression lines, in
contrast, displayed increased class I ceramide synthase activity but reduced
class II ceramide synthase activity. These findings indicate that ORM mediation
of SPT activity differentially regulates functionally distinct ceramide synthase
activities as part of a broader sphingolipid homeostatic regulatory network.
PMID- 27506243
TI - A Cost Analysis of Salbutamol Administration by Metered-Dose Inhalers with
Spacers versus Nebulization for Patients with Wheeze in the Pediatric Emergency
Department: Evidence from Observational Data in Nova Scotia.
AB - BACKGROUND: Despite evidence demonstrating the advantages of metered-dose
inhalers with spacers (MDI-s), nebulization (NEB) remains the primary method of
asthma treatment in some pediatric emergency departments (PEDs). There is a
perception that delivering salbutamol by MDI-s is more costly than by NEB. This
research evaluates the relative costs of MDI-s and NEB using local, hospital
specific, patient-level data. METHODS: Regression models estimated associations
between the salbutamol inhalation method and costs, length of stay (LOS) in the
PED and hospital, and the probability of admission. Our population was a random
sample of 822 patients presenting with wheeze to the PED in 2008/2009. Control
variables included age, sex, triage acuity, time of PED visit, other medications,
and vitals. Costs were calculated using the prices and quantities of medical
resources used per treatment. Probabilistic sensitivity analysis was used.
RESULTS: Treatment with MDI-s versus NEB was associated with an absolute decrease
in hospitalization of 4.4% (p<0.05) and a 25-hour (p<0.001) reduction in average
inpatient stay, after controlling for triage acuity and patient characteristics.
This resulted in savings of $24/patient in the PED and $180/patient overall
(p<0.001). Inpatient care accounted for more than 90% of total patient costs.
CONCLUSIONS: Our results suggest economic gains associated with MDI-s for
salbutamol inhalation in PEDs. Sensitivity analyses show that this conclusion is
not affected by changes in model parameters that may differ by jurisdiction.
Since most facilities already collect the data used for this study, our methods
could be adopted for a cross-jurisdictional account of the cost effectiveness of
MDI-s.
PMID- 27506244
TI - Palladium nanoparticles supported on a nickel pyrazolate metal organic framework
as a catalyst for Suzuki and carbonylative Suzuki couplings.
AB - Methanolic reduction of [PdCl2(CH3CN)2] on a [Ni(2,5-di(1H-pyrazol-4
yl)benzenesulfonate)2] metal organic framework gives rise to Pd(2+)/Pd(0)
nanocomposites with Suzuki and carbonylative Suzuki heterogeneous catalytic
activities.
PMID- 27506242
TI - d-Lactate Dehydrogenase Links Methylglyoxal Degradation and Electron Transport
through Cytochrome c.
AB - Glycolysis generates methylglyoxal (MGO) as an unavoidable, cytotoxic by-product
in plant cells. MGO scavenging is performed by the glyoxalase system, which
produces d-lactate as an end product. d-Lactate dehydrogenase (d-LDH) is encoded
by a single gene in Arabidopsis (Arabidopsis thaliana; At5g06580). It catalyzes
in vitro the oxidation of d-lactate to pyruvate using flavin adenine dinucleotide
as a cofactor; knowledge of its function in the context of the plant cell remains
sketchy. Blue native-polyacrylamide gel electrophoresis of mitochondrial extracts
combined with in gel activity assays using different substrates and tandem mass
spectrometry allowed us to definitely show that d-LDH acts specifically on d
lactate, is active as a dimer, and does not associate with respiratory
supercomplexes of the inner mitochondrial membrane. The combined use of
cytochrome c (CYTc) loss-of-function mutants and respiratory complex III
inhibitors showed that CYTc acts as the in vivo electron acceptor of d-LDH. CYTc
loss-of-function mutants, as well as the d-LDH mutants, were more sensitive to d
lactate and MGO, indicating that they function in the same pathway. In addition,
overexpression of d-LDH and CYTc increased tolerance to d-lactate and MGO
Together with fine-localization of d-LDH, the functional interaction with CYTc in
vivo strongly suggests that d-lactate oxidation takes place in the mitochondrial
intermembrane space, delivering electrons to the respiratory chain through CYTc
These results provide a comprehensive picture of the organization and function of
d-LDH in the plant cell and exemplify how the plant mitochondrial respiratory
chain can act as a multifunctional electron sink for reductant from cytosolic
pathways.
PMID- 27506245
TI - Lithium ion solvation by ethylene carbonates in lithium-ion battery electrolytes,
revisited by density functional theory with the hybrid solvation model and free
energy correction in solution.
AB - Complex formation between lithium (Li(+)) ions and electrolyte molecules would
affect the ionic conductivity through the electrolyte in lithium-ion batteries
(LIBs). We hence revisit the solvation number of Li(+) in the most commonly used
ethylene carbonate (EC) electrolyte. The solvation number n of Li(+)(EC)n in the
first solvation shell of Li(+) is estimated on the basis of the free energy
calculated by the density functional theory combined with a hybrid solvation
model where the explicit solvation shell of Li(+) is immersed in a free volume of
an implicit bulk solvent. This new hybrid solvation (implicit and explicit) model
predicts the most probable solvation number (n = 4) and solvation free energy (
91.3 kcal mol(-1)) of Li(+) in a good agreement with those predicted by
calculations employing simpler solvation models (either implicit or explicit).
The desolvation (n = 2) of Li(0)(EC)n upon reduction near anodes is also well
described with this new hybrid model.
PMID- 27506246
TI - Self-assembly and the hemolysis effect of monodisperse N,N
diethylacrylamide/acrylic acid nanogels with high contents of acrylic acid.
AB - Monodisperse temperature/pH sensitive poly(N,N-diethylacrylamide/acrylic acid)
(P(DEA/AAc)) nanogels with high contents of AAc up to 40 wt% have been prepared.
In this study, it was unexpectedly found that the polydispersity of the nanogels
with 40 wt% AAc strongly depended on the initiator concentration. Monodisperse
P(DEA/AA) nanogels were synthesized only at a very low concentration of
initiator. The phase transition behavior of the nanogels in water can be tuned by
pH and temperature. Due to low polydispersity, the nanogels self-assembled into
colloidal crystals at different temperatures below the volume phase transition
temperature (VPTT). The sharp Bragg peaks of the crystals were significantly blue
shifted as the concentration of the nanogels was increased. In contrast, the
condensed suspensions without crystals still exhibited clear colours resulting
from a short-range order structure. The reflection spectra of the coloured
suspensions showed that the peak wavelength became a bit longer and much broader.
And the reflection intensity of the coloured suspensions was much weaker. Elastic
and coloured crosslinked nanogel networks prepared by a one-pot and rapid light
initiated crosslinking method showed responses to pH and temperature.
Furthermore, the interaction between the nanogels and peptide melittin was
investigated. The results showed that an increasing AAc composition led to more
efficient inhibition of the hemolytic activity of melittin. The nanogels with 40
wt% AAc composition completely inhibited hemolytic activity at a nanogel
concentration of 400 ug ml(-1). Thus, monodisperse P(DEA/AAc) nanogels of high
AAc composition may be developed as efficient substitutes for antibody-based
antidotes. Owing to the combined influence of the periodic structure of the
crystals of the nanogels and an efficient neutralization effect, the P(DEA/AAc)
nanogels show promise to become an integral step for preparing valuable naked-eye
biosensors as simple, cheap and stable substitutes for antibody-based antidotes.
PMID- 27506247
TI - Binding-responsive catalysis of Taq DNA polymerase for the sensitive and
selective detection of cell-surface proteins.
AB - Here we develop a new method for the sensitive and selective detection of cell
surface proteins with an aptamer probe designed for binding-responsive catalysis
of Taq DNA polymerase. Taking the biotin receptor as a model, the method allows
the detection of target protein on surfaces of different types of cancer cells.
PMID- 27506248
TI - The role of confinement and corona crystallinity on the bending modulus of
copolymer micelles measured directly by AFM flexural tests.
AB - We present an approach which makes it possible to directly determine the bending
modulus of single elongated block copolymer micelles. This is done by forming
arrays of suspended micelles onto microfabricated substrates and by performing
three-point bending flexural tests, using an atomic force microscope, on their
suspended portions. By coupling the direct atomic force microscopy measurements
with differential scanning calorimetry data, we show that the presence of a
crystalline corona strongly increases the modulus of the copolymer elongated
micelles. This large increase suggests that crystallites in the corona are larger
and more uniformly oriented due to confinement effects. Our findings together
with this hypothesis open new interesting avenues for the preparation of core
templated polymer fibres with enhanced mechanical properties.
PMID- 27506249
TI - Towards ALD thin film stabilized single-atom Pd1 catalysts.
AB - Supported precious metal single-atom catalysts have shown interesting activity
and selectivity in recent studies. However, agglomeration of these highly mobile
mononuclear surface species can eliminate their unique catalytic properties. Here
we study a strategy for synthesizing thin film stabilized single-atom Pd1
catalysts using atomic layer deposition (ALD). The thermal stability of the Pd1
catalysts is significantly enhanced by creating a nanocavity thin film structure.
In situ infrared spectroscopy and Pd K-edge X-ray absorption spectroscopy (XAS)
revealed that the Pd1 was anchored on the surface through chlorine sites. The
thin film stabilized Pd1 catalysts were thermally stable under both oxidation and
reduction conditions. The catalytic performance in the methanol decomposition
reaction is found to depend on the thickness of protecting layers. While Pd1
catalysts showed promising activity at low temperature in a methanol
decomposition reaction, 14 cycle TiO2 protected Pd1 was less active at high
temperature. Pd L3 edge XAS indicated that the low reactivity compared with Pd
nanoparticles is due to the strong adsorption of carbon monoxide even at 250
degrees C. These results clearly show that the ALD nanocavities provide a basis
for future design of single-atom catalysts that are highly efficient and stable.
PMID- 27506250
TI - Selenazolidine: a selenium containing proline surrogate in peptide science.
AB - In the search for new peptide ligands containing selenium in their sequences, we
investigated l-4-selenazolidine-carboxylic acid (selenazolidine, Sez) as a
proline analog with the chalcogen atom in the gamma-position of the ring. In
contrast to proteinogenic selenocysteine (Sec) and selenomethionine (SeMet), the
incorporation within a peptide sequence of such a non-natural amino acid has
never been studied. There is thus a great interest in increasing the possibility
of selenium insertion within peptides, especially for sequences that do not
possess a sulfur containing amino acid (Cys or Met), by offering other selenated
residues suitable for peptide synthesis protocols. Herein, we have evaluated
selenazolidine in Boc/Bzl and Fmoc/tBu strategies through the synthesis of a
model tripeptide, both in solution and on a solid support. Special attention was
paid to the stability of the Sez residue in basic conditions. Thus, generic
protocols have been optimized to synthesize Sez-containing peptides, through the
use of an Fmoc-Xxx-Sez-OH dipeptide unit. As an example, a new analog of the
vasopressin receptor-1A antagonist was prepared, in which Pro was replaced with
Sez [3-(4-hydroxyphenyl)-propionyl-d-Tyr(Me)-Phe-Gln-Asn-Arg-Sez-Arg-NH2]. Both
proline and such pseudo-proline containing peptides exhibited similar
pharmacological properties and endopeptidase stabilities indicating that the
presence of the selenium atom has minimal functional effects. Taking into account
the straightforward handling of Sez as a dipeptide building block in a
conventional Fmoc/tBu SPPS strategy, this result suggested a wide range of
potential uses of the Sez amino acid in peptide chemistry, for instance as a
viable proline surrogate as well as a selenium probe, complementary to Sec and
SeMet, for NMR and mass spectrometry analytical purposes.
PMID- 27506252
TI - Transferability study of CHO cell clustering assays for monitoring of pertussis
toxin activity in acellular pertussis vaccines.
AB - Current regulations for acellular pertussis (aP) vaccines require that they are
tested for the presence of residual or reversion-derived pertussis toxin (PTx)
activity using the mouse histamine sensitisation test (HIST). Although a CHO cell
clustering assay can be used by manufacturers to verify if sufficient
inactivation of the substance has occurred in-process, this assay cannot be used
at present for the final product due to the presence of aluminium adjuvants which
interfere with mammalian cell cultures. Recently, 2 modified CHO cell clustering
assays which accommodate for the adjuvant effects have been proposed as
alternatives to the HIST. These modified assays eliminate the adjuvant-induced
cytotoxicity either through dilution of the vaccine (called the Direct Method) or
by introducing a porous barrier between the adjuvant and the cells (the Indirect
Method). Transferability and suitability of these methods for testing of products
present on the European market were investigated during a collaborative study
organised by the European Directorate for the Quality of Medicines & HealthCare
(EDQM). Thirteen laboratories participated in this study which included 4 aP
containing vaccines spiked by addition of PTx. This study also assessed the
transferability of a standardised CHO cell clustering assay protocol for use with
non-adjuvanted PTx preparations. Results showed that the majority of laboratories
were able to detect the PTx spike in all 4 vaccines at concentrations of 4 IU/mL
or lower using the Indirect Method. This sensitivity is in the range of the
theoretical sensitivity of the HIST. The Direct Method however did not show the
expected results and would need additional development work.
PMID- 27506253
TI - Effects of Aspect Ratio on Water Immersion into Deep Silica Nanoholes.
AB - Understanding the influence of aspect ratio on water immersion into silica
nanoholes is of significant importance to the etching process of semiconductor
fabrication and other water immersion-related physical and biological processes.
In this work, the processes of water immersion into silica nanoholes with
different height/width aspect ratios (phi = 0.87, 1.92, 2.97, 4.01, 5.06) and
different numbers of water molecules (N = 9986, 19972, 29958, 39944) were studied
by molecular dynamics simulations. A comprehensive analysis has been conducted
about the detailed process of water immersion and the influence of aspect ratios
on water immersion rates. Five distinguishable stages were identified for the
immersion process with all studied models. The results reveal that water can
easily immerse into the silica nanoholes with larger phi and smaller N. The
calculation also suggests that aspect ratios have a greater effect on water
immersion rates for larger N numbers. The mechanism of the water immersion
process is discussed in this work. We also propose a mathematical model to
correlate the complete water immersion process for different aspect ratios.
PMID- 27506254
TI - Electronic properties of embedded graphene: doped amorphous silicon/CVD graphene
heterostructures.
AB - Large-area graphene film is of great interest for a wide spectrum of electronic
applications, such as field effect devices, displays, and solar cells, among many
others. Here, we fabricated heterostructures composed of graphene (Gr) grown by
chemical vapor deposition (CVD) on copper substrate and transferred to SiO2/Si
substrates, capped by n- or p-type doped amorphous silicon (a-Si:H) deposited by
plasma-enhanced chemical vapor deposition. Using Raman scattering we show that
despite the mechanical strain induced by the a-Si:H deposition, the structural
integrity of the graphene is preserved. Moreover, Hall effect measurements
directly on the embedded graphene show that the electronic properties of CVD
graphene can be modulated according to the doping type of the a-Si:H as well as
its phase i.e. amorphous or nanocrystalline. The sheet resistance varies from 360
Omega sq(-1) to 1260 Omega sq(-1) for the (p)-a-Si:H/Gr (n)-a-Si:H/Gr,
respectively. We observed a temperature independent hole mobility of up to 1400
cm(2) V(-1) s(-1) indicating that charge impurity is the principal mechanism
limiting the transport in this heterostructure. We have demonstrated that
embedding CVD graphene under a-Si:H is a viable route for large scale graphene
based solar cells or display applications.
PMID- 27506251
TI - Brain Reward Circuits in Morphine Addiction.
AB - Morphine is the most potent analgesic for chronic pain, but its clinical use has
been limited by the opiate's innate tendency to produce tolerance, severe
withdrawal symptoms and rewarding properties with a high risk of relapse. To
understand the addictive properties of morphine, past studies have focused on
relevant molecular and cellular changes in the brain, highlighting the functional
roles of reward-related brain regions. Given the accumulated findings, a recent,
emerging trend in morphine research is that of examining the dynamics of neuronal
interactions in brain reward circuits under the influence of morphine action. In
this review, we highlight recent findings on the roles of several reward circuits
involved in morphine addiction based on pharmacological, molecular and
physiological evidences.
PMID- 27506255
TI - Temporal Sensing Platform Based on Bipolar Electrode for the Ultrasensitive
Detection of Cancer Cells.
AB - We report a bipolar electrode (BPE) sensing platform for the temporal detection
of cancer cells. Combining the advantages of anodic dissolution and
electrochemiluminescence (ECL), this strategy shows an ultralow detection limit
down to 5 cells/cm(2). At the anode working as the reporting pole, Au NPs were
assembled through DNA double strand, which served as both catalyzer for the ECL
reaction of luminol/H2O2 and seeds for the chemical reduction of Ag, the anodic
dissolution probe. The duration of Ag layer dissolution was positively correlated
with the amount of Ag but negatively related to the controlled potential and the
conductivity of the circuit. Therefore, it was possible to amplify a slight
conductivity change through tuning the other two factors. As the formation of
Ag@Au completely quenched the ECL emission of luminol, the ECL emission recovery
reflected the extent of anodic dissolution. Through monitoring the ECL recovery
time before and after the incubation of cells on the cathode, a few number of
cells could be quantified due to slight difference of the conductivity. This
method shows several merits. First, the combination of anodic dissolution and ECL
significantly increases the detection sensitivity of BPE device. In addition,
this strategy broadens the application of BPE for the ultrasensitive monitoring
of cancer cells, which was applied to investigate the capture efficiencies of
antibodies and aptamers toward MCF-7 and A549.
PMID- 27506256
TI - Bridging the Gap: Dynamic Causal Modeling and Granger Causality Analysis of
Resting State Functional Magnetic Resonance Imaging.
AB - Granger causality (GC) and dynamic causal modeling (DCM) are the two key
approaches used to determine the directed interactions among brain areas. Recent
discussions have provided a constructive account of the merits and demerits. GC,
on one side, considers dependencies among measured responses, whereas DCM, on the
other, models how neuronal activity in one brain area causes dynamics in another.
In this study, our objective was to establish construct validity between GC and
DCM in the context of resting state functional magnetic resonance imaging (fMRI).
We first established the face validity of both approaches using simulated fMRI
time series, with endogenous fluctuations in two nodes. Crucially, we tested both
unidirectional and bidirectional connections between the two nodes to ensure that
both approaches give veridical and consistent results, in terms of model
comparison. We then applied both techniques to empirical data and examined their
consistency in terms of the (quantitative) in-degree of key nodes of the default
mode. Our simulation results suggested a (qualitative) consistency between GC and
DCM. Furthermore, by applying nonparametric GC and stochastic DCM to resting
state fMRI data, we confirmed that both GC and DCM infer similar (quantitative)
directionality between the posterior cingulate cortex (PCC), the medial
prefrontal cortex, the left middle temporal cortex, and the left angular gyrus.
These findings suggest that GC and DCM can be used to estimate directed
functional and effective connectivity from fMRI measurements in a consistent
manner.
PMID- 27506257
TI - Stent Removal in 200 Kidney Transplant Recipients: Nonoperative Versus Endoscopic
Removal.
AB - OBJECTIVES: Inserting a double J stent during kidney transplant has reduced the
rate of urologic complications. Traditionally, a double J stent is removed via
endoscopic intervention. Here, we assessed the safety and efficacy of a
nonoperative method for double J stent removal. MATERIALS AND METHODS: Our study
group included 200 consecutive patients who underwent kidney transplant from
January 2013 to April 2014. Group A consisted of 100 recipients who had a double
J stent that was tied to a Foley catheter with 2-0 silk suture. The stent was
simply removed by taking out the Foley catheter after 3 weeks. Patients in group
A were compared with a second group of 100 kidney transplant patients whose
stents were removed endoscopically 3 weeks later (group B). RESULTS: Patients
were matched between the 2 groups regarding age distribution, male-to-female
patient ratio, deceased versus living donor graft, prevalence of type 2 diabetes
mellitus, and body mass index. The incidence of urinary fistula (3% in group A
and 4% in group B; P = .7), ureteral stenosis (1% in group A and 2% in group B; P
= .56), wound infection (1% in group A and 2% in group B; P = .56), and positive
urine culture (20% in group A and 29% in group B; P = .14) after stent removal
were not significantly different between the 2 groups. CONCLUSIONS: This study
shows that nonoperative removal of a double J stent is a safe and effective
method. This approach is simple, and there is no need for a surgical procedure or
any outpatient surgical intervention.
PMID- 27506258
TI - Modeling of Tacrolimus Exposure in Kidney Transplant According to Posttransplant
Time Based on Routine Trough Concentration Data.
AB - OBJECTIVES: The aim of this study was to develop a pharmacokinetics model
allowing the description of the evolution of tacrolimus exposure in kidney
transplant patients over the first months after transplant, using trough
concentrations of routinely collected blood. MATERIALS AND METHODS: The authors
performed a retrospective analysis of trough concentration data collected from
adult kidney transplant recipients (from 2008 to 2013). The total data set was
divided into a building data set, used to build the structural model, and a
validation data set, used to validate the structural model. (C0 = 133; 26
patients). A pharmacokinetics analysis was carried out by applying a
nonparametric adaptive grid approach. The structural model parameters were
tacrolimus clearance and volume of distribution. RESULTS: In patients in the
building set group, estimated clearance was 3.6 +/- 0.57 L/h and estimated volume
of distribution was 9.9 +/- 1.14 L. No covariate was significantly associated
with tacrolimus clearance or volume of distribution. The model adequately
described tacrolimus dose-normalized trough concentration evolution after
transplant (the plot of individual model predicted versus observed concentrations
resulted in r = 0.84). The prediction performance in the validation group yielded
2.3% mean prediction error and 21.4% root mean squared error. CONCLUSIONS: This
model could be highly useful in the optimization of tacrolimus prescription at
any posttransplant time in kidney transplant patients.
PMID- 27506259
TI - Preoperative Clinical Characteristics That Identify Potential Low-Volume
Transfusion Candidates Among Orthotopic Liver Transplant Patients.
AB - OBJECTIVES: The primary aim of this study was to determine whether specific
preoperative clinical characteristics were associated with low-volume transfusion
in liver transplant recipients. Low-volume transfusion was defined as transfusion
of < 2100 mL of packed red blood cells intraoperatively during liver transplant.
The ability to accurately predict low-volume transfusion could increase patient
safety, decrease complications associated with transfusion, improve blood
management, and decrease transplant case cost. MATERIALS AND METHODS: Data were
retrieved by retrospective chart review of 266 patients who received a liver
transplant at the Mayo Clinic (Jacksonville, FL, USA). The primary outcome was
low-volume transfusion. Associations of preoperative information with low-volume
transfusion were explored using single-variable and multivariable logistic
regression models; missing data were imputed with the sample median for
continuous data and the most frequent category for categorical variables.
RESULTS: Low-volume transfusion occurred in 23% of first-time liver transplant
recipients (62/266 patients; 95% confidence interval, 18%-29%). History of
hepatitis C virus infection (P = .048), history of hepatocellular carcinoma (P =
.050), short cold ischemia time (P = .006), and low international normalized
ratio (P = .002) were independently associated with low-volume transfusion during
liver transplant in a multivariable logistic regression model. CONCLUSIONS:
Multiple studies have shown increased morbidity and mortality after orthotopic
liver transplant when more than 6 U of packed red blood cells are administered
within 24 hours of surgical incision. A method to identify low-volume transfusion
candidates could help predict patient outcomes, decrease blood handling, and
reduce costs. If patients with low-volume transfusion could be identified, fewer
blood products would need to be prepared in advance. Although elevated
preoperative coagulation parameters decrease the probability of low-volume
transfusion, a definitive profile of a low-volume transfusion liver transplant
recipient was not established.
PMID- 27506260
TI - Cytomegalovirus Treatment Strategy After a Liver Transplant: Preemptive Therapy
or Prophylaxis for Cytomegalovirus Seropositive Donor and Recipient.
AB - OBJECTIVES: Cytomegalovirus infections cause the most frequent infection after
solid-organ transplant. While Cytomegalovirus prophylaxis is established in high
risk patients (donor+/ recipient-), data on Cytomegalovirus prophylaxis in other
serostatus constellation are rare. The aim of this study was to evaluate the
influence of Cytomegalovirus treatment strategy after a liver transplant
(preemptive therapy vs general prophylaxis) in the largest group of patients:
Cytomegalovirus seropositive donor and recipient. MATERIALS AND METHODS: Forty
seven seropositive recipients of seropositive donor liver transplants (D+/R+,
2005-2012) were included in this retrospective study. Twenty-one patients
received oral valganciclovir as Cytomegalovirus prophylaxis 100 days after
transplant. Cytomegalovirus infection and Cytomegalovirus disease were monitored
during the first 6 months. RESULTS: A Cytomegalovirus infection could be detected
in 4 out of 47 patients (8.5%), including Cytomegalovirus disease in 2 patients
(Cytomegalovirus pneumonia and Cytomegalovirus-CNS disease). Three of these
patients received no Cytomegalovirus prophylaxis (P = .408). Eight patients
developed a graft failure; this occurred more frequently among patients without
Cytomegalovirus prophylaxis (P = .044). Patients receiving Cytomegalovirus
prophylaxis more often developed leukopenia. No difference was seen regarding the
number of platelets, hemoglobin, and creatinine. CONCLUSIONS: Cytomegalovirus
prophylaxis can minimize the risk of Cytomegalovirus reactivation and graft
failure. However, disadvantages of the prophylaxis as leukopenia should be
considered.
PMID- 27506261
TI - Graft-Versus-Lymphoma Effect Can Be Rapid and Potent in Diffuse Large B-Cell
Lymphoma.
PMID- 27506262
TI - Changes in milk performance and hepatic metabolism in mid-lactating dairy goats
after being fed a high concentrate diet for 10 weeks.
AB - Feeding a high concentrate (HC) diet is a widely used strategy for supporting
high milk yields, yet it may cause certain metabolic disorders. This study aimed
to investigate the changes in milk production and hepatic metabolism in goats fed
different proportions of concentrate in the diet for 10 weeks. In total, 12 mid
lactating goats were randomly assigned to an HC diet (65% concentrate of dry
matter, n=6) or a low concentrate (LC) diet (35% concentrate of dry matter, n=6).
Compared with LC, HC goats produced greater amounts of volatile fatty acids and
produced more milk and milk lactose, fat and protein (P<0.01). HC goats showed a
greater concentration of ATP, NAD, plasma non-esterified fatty acids and hepatic
triglycerides than LC goats (P<0.05). Real-time PCR results showed that messenger
RNA (mRNA) expression of gluconeogenic genes, namely, glucose-6-phosphatase,
pyruvate carboxylase and phosphoenolpyruvate carboxykinase were significantly up
regulated and accompanied greater gluconeogenic enzyme activities in the liver of
HC goats. Moreover, the expression of hepatic lipogenic genes including sterol
regulatory element-binding protein 1c, fatty acid synthase and diacylglycerol
acyltransferase mRNA was also up-regulated by the HC diet (P<0.05). HC goats had
greater hepatic phosphorylation of AMP-activated protein kinase than LC (P<0.05).
Furthermore, histone-3-lysine-27-acetylation contributed to this elevation of
gluconeogenic gene expression. These results indicate that lactating goats fed an
HC diet for 10 weeks produced more milk, which was associated with up-regulated
gene expression and enzyme activities involved in hepatic gluconeogenesis and
lipogenesis.
PMID- 27506264
TI - The importance of bone shortening in digital replantation.
PMID- 27506263
TI - IFPA meeting 2015 workshop report IV: placenta and obesity; stem cells of the
feto-maternal interface; placental immunobiology and infection.
AB - Workshops are an important part of the IFPA annual meeting as they allow for
discussion of specialised topics. At the 2015 IFPA annual meeting there were 12
themed workshops, three of which are summarized in this report. These workshops
related to various aspects of placental biology and collectively covered areas of
obesity and the placenta, stem cells of the feto-maternal interface, and
placental immunobiology and infection.
PMID- 27506265
TI - Perforator-based propeller flaps for leg reconstruction in pediatric patients.
AB - BACKGROUND: Perforator-based propeller flaps provide adequate soft tissue
coverage for leg reconstruction. The aim of this study was to assess the
versatility and reliability of the use of propeller flaps for leg reconstruction
in pediatric patients. METHOD: Seven male pediatric patients ranging in age from
2 to 13 years with a mean age of 6.7 underwent perforator-based propeller flap
surgery over a four-year period. The defects resulted from burn injuries (n = 4)
and traffic accidents (n = 3). The injuries were located on the ankles of four
patients and on the knee, anterior lower tibia, and foot dorsum of the other
three patients, respectively. RESULTS: The flap sizes ranged from 5 * 3 to 10 * 6
cm with a mean flap size of 7.6 * 4.3 cm. Flap harvesting time ranged from 38 to
56 m with a mean of 46 m. The rotation degree range of the flaps was from 90
degrees to 180 degrees . The propeller flaps were based on the posterior tibial
artery (n = 4), anterior tibial artery (n = 2), and the descending branch of the
lateral circumflex femoral artery (n = 1). All flaps survived completely without
surgical complication; however, one patient developed disseminated intravascular
coagulation syndrome two days post-surgery and died within four days. CONCLUSION:
Perforator-based propeller flap reconstruction is a safe, reliable, and versatile
method for lower extremities in pediatric patients; however, it requires
meticulous surgical dissection and extreme patience during the surgical
procedure.
PMID- 27506266
TI - Neurobiological degeneracy: A key property for functional adaptations of
perception and action to constraints.
AB - A crucial aspect of understanding human behavior relates to how perception and
action sub-systems are integrated during coordinated and controlled movement in
goal-directed activity. Here we discuss how a neurobiological system property,
degeneracy (i.e., many coordinative structures to achieve one function), can help
us understand how skilled individuals functionally adapt perception and action to
interacting constraints during performance. Since most research investigating
degeneracy has been conducted in neuroanatomy, genetics and theoretical
neurobiology, here we clarify how degeneracy is exhibited in perceptual-motor
systems. Using an ecological dynamics framework, we highlight how degeneracy
underpins the functional role of movement coordination variability in performance
of multi-articular tasks. Following that, we discuss how degenerate
neurobiological systems are able to exploit system stability and flexibility in
their movement coordination. Third, we show how better coupling of information
and movement could lead individuals to explore functionally degenerate behaviors.
Last, we explore how degeneracy can support pluri-potentiality (i.e., one
coordinative structure for many perceptual-motor functions) as a way toward
innovation or refinement in performance.
PMID- 27506267
TI - Understanding metastable phase transformation during crystallization of RDX, HMX
and CL-20: experimental and DFT studies.
AB - Multiphase growth during crystallization severely affects deliverable output of
explosive materials. Appearance and incomplete transformation of metastable
phases are a major source of polymorphic impurities. This article presents a
methodical and molecular level understanding of the metastable phase
transformation mechanism during crystallization of cyclic nitramine explosives,
viz. RDX, HMX and CL-20. Instantaneous reverse precipitation yielded metastable
gamma-HMX and beta-CL-20 which undergo solution mediated transformation to the
respective thermodynamic forms, beta-HMX and epsilon-CL-20, following 'Ostwald's
rule of stages'. However, no metastable phase, anticipated as beta-RDX, was
evidenced during precipitation of RDX, which rather directly yielded the
thermodynamically stable alpha-phase. The gamma->beta-HMX and beta->epsilon-CL-20
transformations took 20 and 60 minutes respectively, whereas formation of alpha
RDX was instantaneous. Density functional calculations were employed to identify
the possible transition state conformations and to obtain activation barriers for
transformations at wB97XD/6-311++G(d,p)(IEFPCM)//B3LYP/6-311G(d,p) level of
theory. The computed activation barriers and lattice energies responsible for
transformation of RDX, HMX and CL-20 metastable phases to thermodynamic ones
conspicuously supported the experimentally observed order of phase stability.
This precise result facilitated an understanding of the occurrence of a
relatively more sensitive and less dense beta-CL-20 phase in TNT based melt-cast
explosive compositions, a persistent and critical problem unanswered in the
literature. The crystalline material recovered from such compositions revealed a
mixture of beta- and epsilon-CL-20. However, similar compositions of RDX and HMX
never showed any metastable phase. The relatively long stability with the highest
activation barrier is believed to restrict complete beta->epsilon-CL-20
transformation during processing. Therefore a method is suggested to overcome
this issue.
PMID- 27506268
TI - 2D nanostructures for water purification: graphene and beyond.
AB - Owing to their atomically thin structure, large surface area and mechanical
strength, 2D nanoporous materials are considered to be suitable alternatives for
existing desalination and water purification membrane materials. Recent progress
in the development of nanoporous graphene based materials has generated enormous
potential for water purification technologies. Progress in the development of
nanoporous graphene and graphene oxide (GO) membranes, the mechanism of graphene
molecular sieve action, structural design, hydrophilic nature, mechanical
strength and antifouling properties and the principal challenges associated with
nanopore generation are discussed in detail. Subsequently, the recent
applications and performance of newly developed 2D materials such as 2D boron
nitride (BN) nanosheets, graphyne, molybdenum disulfide (MoS2), tungsten
chalcogenides (WS2) and titanium carbide (Ti3C2Tx) are highlighted. In addition,
the challenges affecting 2D nanostructures for water purification are highlighted
and their applications in the water purification industry are discussed. Though
only a few 2D materials have been explored so far for water treatment
applications, this emerging field of research is set to attract a great deal of
attention in the near future.
PMID- 27506269
TI - A Physiologically Based Pharmacokinetic Model to Describe Artemether
Pharmacokinetics in Adult and Pediatric Patients.
AB - Artemether is co-administered with lumefantrine as part of a fixed-dose
combination therapy for malaria in both adult and pediatric patients. However,
artemether exposure is higher in younger infants (1-3 months) with a lower body
weight (<5 kg) as compared to older infants (3-6 months) with a higher body
weight (>=5 to <10 kg), children, and adults. In contrast, lumefantrine exposure
is similar in all age groups. This article describes the clinically observed
artemether exposure data in pediatric populations across various age groups (1
month to 12 years) and body weights (<5 or >=5 kg) using physiologically based
pharmacokinetic (PBPK) mechanistic models. A PBPK model was developed using
artemether physicochemical, biopharmaceutic, and metabolic properties together
with known enzyme ontogeny and pediatric physiology. The model was verified using
clinical data from adult patients after multiple doses of oral artemether, and
was then applied to simulate the exposure in children and infants. The simulated
PBPK concentration-time profiles captured observed clinical data. Consistent with
the clinical data, the PBPK model simulations indicated a higher artemether
exposure for younger infants with lower body weight. A PBPK model developed for
artemether reliably described the clinical data from adult and pediatric
patients.
PMID- 27506270
TI - Mannitol/l-Arginine-Based Formulation Systems for Freeze Drying of Protein
Pharmaceuticals: Effect of the l-Arginine Counter Ion and Formulation Composition
on the Formulation Properties and the Physical State of Mannitol.
AB - Previous studies have shown that protein storage stability in freeze-dried l
arginine-based systems improved in the presence of chloride ions. However,
chloride ions reduced the glass transition temperature of the freeze concentrate
(Tg') and made freeze drying more challenging. In this study, l-arginine was
freeze dried with mannitol to obtain partially crystalline solids that can be
freeze dried in a fast process and result in elegant cakes. We characterized the
effect of different l-arginine counter ions on physicochemical properties of
mannitol compared with mannitol/sucrose systems. Thermal properties of
formulations with different compositions were correlated to thermal history
during freeze drying and to physicochemical properties (cake appearance, residual
moisture, reconstitution time, crystallinity). Partially crystalline solids were
obtained even at the highest l-arginine level (mannitol:l-arginine of 2:1) used
in this study. All l-arginine-containing formulations yielded elegant cakes. Only
cakes containing l-arginine chloride and succinate showed a surface "crust"
formed by phase separation. X-ray powder diffraction showed that inhibition of
mannitol crystallization was stronger for l-arginine compared with sucrose and
varied with the type of l-arginine counter ion. The counter ion affected mannitol
polymorphism and higher levels of mannitol hemi-hydrate were obtained at high
levels of l-arginine chloride.
PMID- 27506271
TI - Influence of Adsorption on Proteins and Amyloid Detection by Silicon Nitride
Nanopore.
AB - For the past 2 decades, emerging single-nanopore technologies have opened the
route to multiple sensing applications. Besides DNA sensing, the identification
of proteins and amyloids is a promising field for early diagnosis. However, the
influence of the interactions between the nanopore surface and proteins should be
taken into account. In this work, we have selected three proteins (avidin,
lysozyme, and IgG) that exhibit different affinities with the SiNx surface, and
we have also examined lysozyme amyloid. Our results show that the piranha
treatment of SiNx significantly decreases protein adsorption. Moreover, we have
successfully detected all proteins (pore diameter 17 nm) and shown the
possibility of discriminating between denatured lysozyme and its amyloid. For all
proteins, the capture rates are lower than expected, and we evidence that they
are correlated with the affinity of proteins to the surface. Our result confirms
that proteins interacting only with the nanopore surface wall stay long enough to
be detected. For lysozyme amyloid, we show that the use of the nanopore is
suitable for determining the number of monomer units even if only the proteins
interacting with the nanopore are detected.
PMID- 27506272
TI - Hepaticoplasty prevents cholangitis after pancreaticoduodenectomy in patients
with small bile ducts.
AB - BACKGROUND: To reduce cholangitis after pancreaticoduodenectomy (PD), we perform
'hepaticoplasty', in which the left side of the bile duct is cut to widen the
diameter of the bile duct wall before hepaticojejunostomy. The aim of this study
was to clarify the usefulness of hepaticoplasty to reduce cholangitis after PD.
METHODS: From January 2002 through December 2010, 161 patients underwent PD and
were enrolled in this study. Patient demographics, surgical factors, and clinical
and biochemical parameters were evaluated to examine the factors predictive of
cholangitis after PD and confirm the usefulness of hepaticoplasty. RESULTS:
Cholangitis after PD occurred in 13 patients (8.1%). Multivariate analysis
revealed that the ratio of the postoperative bile duct diameter to that before
surgery was the only independent risk factor for cholangitis after PD (p =
0.0012). In the small bile duct group, in which the diameter was <=15 mm before
surgery (n = 99), hepaticoplasty reduced the narrowing of the bile duct after PD,
and no cholangitis occurred. There were no complications related to
hepaticoplasty. CONCLUSIONS: The ratio of postoperative reduction of the bile
duct diameter to that before surgery was found to be the only risk factor for
cholangitis after PD. Patients with a small bile duct of <=15 mm in diameter
preoperatively might benefit from hepaticoplasty to widen the bile duct diameter
and prevent cholangitis after PD.
PMID- 27506274
TI - Purification and characterization of xylitol dehydrogenase with l-arabitol
dehydrogenase activity from the newly isolated pentose-fermenting yeast
Meyerozyma caribbica 5XY2.
AB - Meyerozyma caribbica strain 5XY2, which was isolated from an alcohol fermentation
starter in Thailand, was found to catabolize l-arabinose as well as d-glucose and
d-xylose. The highest production amounts of ethanol from d-glucose, xylitol from
d-xylose, and l-arabitol from l-arabinose were 0.45 g/g d-glucose, 0.60 g/g d
xylose, and 0.61 g/g l-arabinose with 21.7 g/L ethanol, 20.2 g/L xylitol, and
30.3 g/l l-arabitol, respectively. The enzyme with l-arabitol dehydrogenase (LAD)
activity was purified from the strain and found to exhibit broad specificity to
polyols, such as xylitol, d-sorbitol, ribitol, and l-arabitol. Xylitol was the
preferred substrate with Km=16.1 mM and kcat/Km=67.0 min-1mM-1, while l-arabitol
was also a substrate for the enzyme with Km=31.1 mM and kcat/Km=6.5 min-1 mM-1.
Therefore, this enzyme from M. caribbica was named xylitol dehydrogenase (McXDH).
McXDH had an optimum temperature and pH at 40 degrees C and 9.5, respectively.
The McXDH gene included a coding sequence of 1086 bp encoding a putative 362
amino acid protein of 39 kDa with an apparent homopentamer structure. Native
McXDH and recombinant McXDH exhibited relative activities toward l-arabitol of
approximately 20% that toward xylitol, suggesting the applicability of this
enzyme with the functions of XDH and LAD to the development of pentose-fermenting
Saccharomyces cerevisiae.
PMID- 27506275
TI - Nucleophilic reactivity and electrocatalytic reduction of halogenated organic
compounds by nickel o-phenylenedioxamidate complexes.
AB - A growing number of halogenated organic compounds have been identified as
hazardous pollutants. Although numerous advanced oxidative processes have been
developed to degrade organohalide compounds, reductive and nucleophilic molecular
approaches to dehalogenate organic compounds have rarely been reported. In this
manuscript, we employ nickel(ii)-ate complexes bearing the o-phenylenebis(N
methyloxamide) (Me2opba) tetraanionic ligand as nucleophilic reagents that can
react with alkyl halides (methyl up to the bulky isobutyl) by O-alkylation to
give their respective imidate products. Four new nickel(ii) complexes have been
characterized by X-ray crystallography, and the salient structural parameters and
FT-IR vibrational bands (~1655 cm(-1)) concur with their assignment as the
imidate tautomeric form. To the best of our knowledge, this is the first report
on the nucleophilic reactivity of Ni(II)(Me2opba) with halogenated organic
compounds. The parent nickel(ii) Me2opba complex exhibits reversible
electrochemical oxidation and reduction behavior. As a proof of concept,
Ni(II)(Me2opba) and its alkylated congeners were utilized for the
electrocatalytic reduction of chloroform, as a representative, simple
polyhalogenated organic molecule that could arise from the oxidative treatment of
organic compounds by chlorination. Modest turnover numbers of up to 6 were
recorded, with dichloromethane identified as one of the possible products. Future
efforts are directed towards bulkier -ate complexes that possess metal-centered
instead of ligand-centered nucleophilic activity to create more effective
electrocatalysts for the reduction of halogenated organic compounds.
PMID- 27506276
TI - Effects of dietary Spirulina platensis on growth performance, humoral and mucosal
immune responses and disease resistance in juvenile great sturgeon (Huso huso
Linnaeus, 1754).
AB - Dietary supplementation of Spirulina platensis at different levels (0% control,
2.5%, 5% and 10%) was evaluated to find out the effects on growth performance,
digestive enzyme activities, humoral and skin innate immune responses and disease
resistance in the great sturgeon (Huso huso). After 8 weeks of experimental
trial, growth parameters, intestinal lactic acid bacteria count, protease and
lipase activities were significantly high in 10% S. platensis fed group (P <
0.05). Similarly, in this group, respiratory burst activity of leucocytes and
total protein of serum were also significantly high. Furthermore, supplementation
of S. platensis at 5 or 10% exhibited higher serum IgM and lysozyme activity than
the other experimental groups (P < 0.05). On the contrary, serum triglycerides
and number of blood lymphocytes were lower in experimental groups than that of
control group. Total proteins, lysozyme, protease and esterase, as well as in
vitro bactericidal activity (against Streptococcus iniae, Yersinia ruckeri,
Aeromonas hydrophila and Lactococcus garviea) were significantly high in skin
mucus from fish fed 5% and 10% S. platensis, while, alkaline phosphatase was
significantly high in fish fed 10% S. platensis (P < 0.05). Further, fish
infected with Streptococcus iniae bacteria increased mortality, but it was
alleviated by a diet supplemented with S. platensis. The present results
demonstrate that this dietary supplementation with S. platensis (mainly at 10%
level) could be useful for maintaining the overall health status of great
sturgeon.
PMID- 27506277
TI - Identification and characterization of an 18.4kDa antimicrobial truncation from
shrimp Litopenaeus vannamei hemocyanin upon Vibrio parahaemolyticus infection.
AB - Hemocyanin (HMC) is a multifunctional protein which plays many essential roles in
invertebrate organism. Recently more and more immune-related functions have been
discovered on this protein. Here the shrimp was infected with Vibrio
parahaemolyticus and the shrimp sera were analyzed by two-dimensional gel
electrophoresis. Totally 15 spots were identified as significantly up-regulated
spots and further analyzed by MALDI-TOF/TOF mass spectrometry (MS). Four of them
were identified as HMC derived truncations (HMCS1, HMCS3, HMCS4 and HMCS5). The
HMCS4 primary sequence was further determined via Edman N terminal sequencing,
MALDI-TOF MS and amino acid sequence alignment. The result indicated that the
HMCS4 was a 165aa fragment from shrimp HMC small subunit C-terminal. The HMCS4
immunological activities were further analyzed by agglutination experiment and
antibacterial assay in vitro. The results showed that the recombinant HMCS4
(rHMCS4) had strong agglutination and antibacterial activities against pathogenic
bacteria at the optimum bacteriostasis concentration. In addition, the HMCS4
immunological activities were explored via mortality assay in vivo. The shrimp
was challenged with V. parahaemolyticus and rHMCS4 V. parahaemolyticus mixture
separately. The shrimp mortality rate was significantly decreased at 96 h post
infection with rHMCS4 injection. Our data showed that shrimp HMC truncation
generation upon infection was an effective immune response against invaded
pathogens. Moreover, these findings may have some potential applications in
shrimp industry.
PMID- 27506278
TI - Disparities in Provider Recommendation of Human Papillomavirus Vaccination for
U.S. Adolescents.
AB - PURPOSE: To determine the prevalence of and examine factors associated with
provider recommendation of human papillomavirus vaccination for U.S. adolescents.
METHODS: Multivariable logistic regression analyses were performed using data
from the National Immunization Survey-Teen 2014 on 34,478 adolescents aged 13-17
years. RESULTS: Overall prevalence of vaccine recommendation was 72.6% for girls
and 51.8% for boys. Lower rates were observed among girls aged 13 years, living
below poverty line, adolescents of lesser educated mothers, and those residing in
the South. Overall, girls had higher odds of vaccine recommendation (odds ratio
[OR] = 2.57; 95% confidence interval [CI] = 2.35-2.82). Correlates of higher
vaccine recommendation for girls were: older age-17 versus 13 (OR = 1.51; 95% CI
= 1.20-1.89), living above versus below poverty line, and residing in Northeast
(OR = 1.45; 95% CI = 1.21-1.73) and Midwest (OR = 1.29; 95% CI = 1.11-1.50)
versus South. For boys, correlates of higher vaccine recommendation were: non
Hispanic black (OR = 1.30; 95% CI = 1.07-1.58) and Hispanic (OR = 1.24; 95% CI =
1.03-1.48) versus non-Hispanic white race and residing in Northeast (OR = 1.79;
95% CI = 1.54-2.08) and West (OR = 1.41; 95% CI = 1.17-1.70) versus South. Other
factors associated with vaccine recommendation were having a college-educated
mother and frequent doctor visits in the past 12 months. CONCLUSIONS: This study
highlights significant disparities in provider recommendation of human
papillomavirus vaccination for U.S. adolescents. Findings suggest possible areas
for tailored interventions to bridge the gap in vaccine recommendation and uptake
in high-risk populations.
PMID- 27506279
TI - A Cross-Sectional Study on the Perceptions and Practices of Teenagers With
Inflammatory Bowel Disease About Repeated Stool Sampling.
AB - PURPOSE: Repeated stool sampling to monitor disease activity is increasingly used
in teenagers with inflammatory bowel disease (IBD). Knowledge about their
perceptions and practices regarding collection of feces will increase the success
rate of this monitoring strategy. METHODS: We sent a survey to teenagers with IBD
treated in an academic center. RESULTS: Seventy-two of 122 invited teenagers
completed the survey (response rate 59%; median age 15 years (interquartile
range, 13-17). Eighty-five percent reported that stool sampling is normally
initiated with help of their parents or caretakers. Seventy-eight percent of
respondents say that their parents assist with the placement of stool in the
container. CONCLUSIONS: Teenagers do not feel embarrassed by the idea of stool
sampling, but an active role of the parents or caretakers is an important
prerequisite for maintaining a stool-based disease monitoring system. Autonomy in
stool sampling is an essential skill required for a successful transition to
adult-centered IBD care.
PMID- 27506280
TI - Special issue on 'Cytoskeletal proteins in health and neurodegenerative disease'.
AB - The cytoskeleton is the major intracellular structure that determines the
morphology of neurons and maintains their structural integrity. It is therefore
not surprising that a disturbance of cytoskeletal structure and functionunderlies
many neurodegenerative diseases. This special issue brings together current
information on the three majorneuronal cytoskeletal filament systems,
microtubules, microfilaments and neurofilaments, and aims to provide a
comprehensive overview of the role of the key components of these three systems
under both physiological and pathological conditions. It therefore also addresses
the role of microtubule-associated proteins (with a focus on tau) and motor
proteins (with a focus on kinesin).
PMID- 27506281
TI - Heterodinuclear Pt(iv)-Ru(ii) anticancer prodrugs to combat both drug resistance
and tumor metastasis.
AB - A novel approach to design bimetallic anticancer drug candidates with the
capability to combat both drug resistance and tumor metastasis is reported. These
water-soluble bifunctional Pt(iv)-Ru(ii) heterodinuclear complexes with a unique
mode of action display up to 2-orders of magnitude enhanced cytotoxicity in
cisplatin-resistant cells and significantly impede cancer cell migration.
PMID- 27506282
TI - Epilepsy-associated tumours: what epileptologists should know about
neuropathology, terminology, and classification systems.
AB - Brain tumours are an ever-challenging issue in neurology and related medical
disciplines. This applies in particular to brain tumours associated with
childhood-onset epilepsies, in which seizures are the presenting and only
neurological symptom, as our current understanding of the biology and clinical
behaviour of an individual tumour is far from being evidence-based. Prospective
and randomized clinical trials are lacking in the field of epilepsy-associated
tumours and a review of the current literature evokes more questions than
provides answers. In this review, current areas of controversy in neuropathology,
as well as terminology and classification, are discussed from an epileptologist's
perspective. An illustrative case report exemplifies this controversy to further
promote interdisciplinary discussion and novel research avenues towards
comprehensive patient management in the near future.
PMID- 27506283
TI - Local lateral environment of the molecules at the surface of DMSO-water mixtures.
AB - Molecular dynamics simulations of the liquid-vapour interface of dimethyl
sulphoxide (DMSO)-water mixtures of 11 different compositions, including two neat
systems are performed on the canonical (N, V, T) ensemble at 298 K. The molecules
constituting the surface layer of these systems are selected by means of the
identification of the truly interfacial molecules (ITIM) method, and their local
lateral environment at the liquid surface is investigated by performing Voronoi
analysis. The obtained results reveal that both molecules prefer to be in a mixed
local environment, consisting of both kinds of molecules, at the liquid surface,
and this preference is even stronger here than in the bulk liquid phase. Neat
like patches, in which a molecule is surrounded by like neighbours, are not
found. However, vacancies that are surrounded solely by water molecules are
observed at the liquid surface. Our results show that strongly hydrogen bonded
DMSO.H2O complexes, known to exist in the bulk phase of these mixtures, are
absent from the liquid surface.
PMID- 27506284
TI - Dipyrrolylpyrimidines as anion-responsive pi-electronic systems.
AB - Dipyrrolylpyrimidines synthesized by coupling reactions exhibited anion-binding
abilities with the inversion of pyrrole rings. In the solid state, anion
complexes of dipyrrolylpyrimidines formed charge-by-charge columnar structures in
combination with counter cations.
PMID- 27506285
TI - Acute calcific tendinitis of the longus colli muscle.
PMID- 27506286
TI - Chemical composition and methane potential of commercial food wastes.
AB - There is increasing interest in anaerobic digestion in the U.S. However, there is
little information on the characterization of commercial food waste sources as
well as the effect of waste particle size on methane yield. The objective of this
research was to characterize four commercial food waste sources: (1) university
dining hall waste, (2) waste resulting from prepared foods and leftover produce
at a grocery store, (3) food waste from a hotel and convention center, and (4)
food preparation waste from a restaurant. Each sample was tested in triplicate 8L
batch anaerobic digesters after shredding and after shredding plus grinding.
Average methane yields for the university dining, grocery store, hotel, and
restaurant wastes were 363, 427, 492, and 403mL/dry g, respectively. Starch
exhibited the most complete consumption and particle size did not significantly
affect methane yields for any of the tested substrates. Lipids represented 59-70%
of the methane potential of the fresh substrates.
PMID- 27506287
TI - Special Issue 7th International Granulation Workshop, June 2015.
PMID- 27506288
TI - Wafer-scale high-resolution patterning of reduced graphene oxide films for
detection of low concentration biomarkers in plasma.
AB - Given that reduced graphene oxide (rGO)-based biosensors allow disposable and
repeatable biomarker detection at the point of care, we developed a wafer-scale
rGO patterning method with mass productivity, uniformity, and high resolution by
conventional micro-electro-mechanical systems (MEMS) techniques. Various rGO
patterns were demonstrated with dimensions ranging from 5 MUm up to several
hundred MUm. Manufacture of these patterns was accomplished through the
optimization of dry etching conditions. The axis-homogeneity and uniformity were
also measured to verify the uniform patternability in 4-inch wafer with dry
etching. Over 66.2% of uniform rGO patterns, which have deviation of resistance
within range of +/-10%, formed the entire wafer. We selected amyloid beta (Abeta)
peptides in the plasma of APP/PS1 transgenic mice as a study model and measured
the peptide level by resistance changes of highly uniform rGO biosensor arrays.
Abeta is a pathological hallmark of Alzheimer's disease and its plasma
concentration is in the pg mL(-1) range. The sensor detected the Abeta peptides
with ultra-high sensitivity; the LOD was at levels as low as 100 fg mL(-1). Our
results provide biological evidences that this wafer-scale high-resolution
patterning method can be used in rGO-based electrical diagnostic devices for
detection of low-level protein biomarkers in biofluids.
PMID- 27506289
TI - Non-absorbable apple procyanidins prevent obesity associated with gut microbial
and metabolomic changes.
AB - Several studies have suggested that flavan-3-ols/procyanidins are associated with
a reduced risk of developing obesity and metabolic syndrome. However, the role of
highly polymeric procyanidins (PP), which are major non-absorbable flavonoids, in
the biological effects, is not completely understood. Here, we show that 0.5% PP
administration for 20 weeks alleviated obesity and regulate expression of genes
related to lipid metabolism in C57BL/6J mice fed a high-fat/high-sucrose diet. PP
treatment attenuated weight gain and inflammatory effects including
lipopolysaccharide and gut permeability. Additionally, metabolic urine profiling
using high-performance liquid chromatography-quadrupole time-of-flight/mass
spectrometry demonstrated that PP-treatment decreased the levels of endogenous
metabolites associated with insulin resistance. Furthermore, microbial 16S rRNA
gene sequencing of the cecum demonstrated that PP administration markedly
decreased the Firmicutes/Bacteroidetes ratio and increased eight times the
proportion of Akkermansia. These data suggest that PPs influence the gut
microbiota and the intestinal metabolome to produce beneficial effects on
metabolic homeostasis.
PMID- 27506290
TI - Turning the respiratory flexibility of Mycobacterium tuberculosis against itself.
AB - The Mycobacterium tuberculosis (Mtb) electron transport chain (ETC) has received
significant attention as a drug target, however its vulnerability may be affected
by its flexibility in response to disruption. Here we determine the effect of the
ETC inhibitors bedaquiline, Q203 and clofazimine on the Mtb ETC, and the value of
the ETC as a drug target, by measuring Mtb's respiration using extracellular flux
technology. We find that Mtb's ETC rapidly reroutes around inhibition by these
drugs and increases total respiration to maintain ATP levels. Rerouting is
possible because Mtb rapidly switches between terminal oxidases, and, unlike
eukaryotes, is not susceptible to back pressure. Increased ETC activity
potentiates clofazimine's production of reactive oxygen species, causing rapid
killing in vitro and in a macrophage model. Our results indicate that combination
therapy targeting the ETC can be exploited to enhance killing of Mtb.
PMID- 27506291
TI - Scalable hybrid chemical manufacture to photothermal therapy: PEG-capped
phototransducers.
AB - Ag-TiO2@polyethylene glycol (PEG) nanoparticles were continuously obtained in a
single-pass configuration by appropriately reacting freshly flame-synthesized
TiO2 with Ag formed in an ultrasonic aqueous medium containing PEG. When the
proposed synthesis was kept constant, the production rate for Ag-TiO2@PEG
nanoparticles reached approximately 3 g/h while only using a combination of a lab
scale inverse-diffusion flame (16 mm head diameter) and an ultrasonic Ag(I) cell
(50 mL). The synthesized nanoparticles were employed as inducers for in vitro
photoinduced therapy to kill cancer cells at different light wavelengths.
Measurements of the nanoparticle cytotoxicity revealed that PEG incorporation
with the Ag-TiO2 particles significantly decreased the cytotoxicity (cell
viability of more than ~91% at 200 MUg mL(-1) particle concentration) of Ag, and
this was comparable with that of TiO2 particles (cell viability of more than
~90%). When 632 nm and 808 nm light was applied to the nanoparticles in the HeLa
cells, the viability of the cells was significantly affected [decreased to ~4%
(632 nm) and ~26% (808 nm) at 200 MUg mL(-1), 5 min irradiation time] by surface
plasmon resonance heating and photothermal therapy.
PMID- 27506292
TI - The influence of distance and quality of care on place of delivery in rural
Ghana.
AB - Facility delivery is an important aspect of the strategy to reduce maternal and
newborn mortality. Geographic access to care is a strong determinant of facility
delivery, but few studies have simultaneously considered the influence of
facility quality, with inconsistent findings. In rural Brong Ahafo region in
Ghana, we combined surveillance data on 11,274 deliveries with quality of care
data from all 64 delivery facilities in the study area. We used multivariable
multilevel logistic regression to assess the influence of distance and several
quality dimensions on place of delivery. Women lived a median of 3.3 km from the
closest delivery facility, and 58% delivered in a facility. The probability of
facility delivery ranged from 68% among women living 1 km from their closest
facility to 22% among those living 25 km away, adjusted for confounders. Measured
quality of care at the closest facility was not associated with use, except that
facility delivery was lower when the closest facility provided substandard care
on the EmOC dimension. These results do not imply, however, that we should
increase geographic accessibility of care without improving facility quality.
While this may be successful in increasing facility deliveries, such care cannot
be expected to reduce maternal and neonatal mortality.
PMID- 27506294
TI - The secret life of Pickering emulsions: particle exchange revealed using two
colours of particle.
AB - Emulsion droplets stabilised by colloidal particles (Pickering emulsions) can be
highly stable, so it is unsurprising that they are beginning to be exploited
industrially. The individual colloidal particles have interfacial attachment
energies that are vastly larger than the thermal energy, hence they are usually
thought of as being irreversibly adsorbed. Here we show, for the first time,
particles being exchanged between droplets in a Pickering emulsion. This occurs
when the emulsion contains droplets that share particles, often called bridging.
By starting with two emulsions showing bridging, each stabilised by a different
colour of particle, the dynamics can be studied as they are gently mixed together
on a roller bank. We find that particle exchange occurs by two routes: firstly,
during a period of unbridging and rebridging whose duration can be tuned by
varying the wettability of the particles, and secondly, during very rare events
when particles are ejected from one droplet and re-adsorbed onto another.
PMID- 27506293
TI - Exosome-mediated Delivery of Hydrophobically Modified siRNA for Huntingtin mRNA
Silencing.
AB - Delivery represents a significant barrier to the clinical advancement of
oligonucleotide therapeutics for the treatment of neurological disorders, such as
Huntington's disease. Small, endogenous vesicles known as exosomes have the
potential to act as oligonucleotide delivery vehicles, but robust and scalable
methods for loading RNA therapeutic cargo into exosomes are lacking. Here, we
show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently
load into exosomes upon co-incubation, without altering vesicle size distribution
or integrity. Exosomes loaded with hsiRNAs targeting Huntingtin mRNA were
efficiently internalized by mouse primary cortical neurons and promoted dose
dependent silencing of Huntingtin mRNA and protein. Unilateral infusion of hsiRNA
loaded exosomes, but not hsiRNAs alone, into mouse striatum resulted in bilateral
oligonucleotide distribution and statistically significant bilateral silencing of
up to 35% of Huntingtin mRNA. The broad distribution and efficacy of hsiRNA
loaded exosomes delivered to brain is expected to advance the development of
therapies for the treatment of Huntington's disease and other neurodegenerative
disorders.
PMID- 27506295
TI - Epidermal growth factor gene is a newly identified candidate gene for gout.
AB - Chromosome 4q25 has been identified as a genomic region associated with gout.
However, the associations of gout with the genes in this region have not yet been
confirmed. Here, we performed two-stage analysis to determine whether variations
in candidate genes in the 4q25 region are associated with gout in a male Chinese
Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs)
in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes
in the 4q25 region in 480 male gout patients and 480 controls. The SNP
rs12504538, located in the elongation of very-long-chain-fatty-acid-like family
member 6 gene (Elovl6), was found to be associated with gout susceptibility
(Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping
analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF)
and its flanking regions in 1017 male patients gout and 1897 healthy male
controls. We observed a significant association between the T allele of EGF
rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67-0.88,
Padjusted = 6.42 * 10(-3)). These results provide the first evidence for an
association between the EGF rs2298999 C/T polymorphism and gout. Our findings
should be validated in additional populations.
PMID- 27506296
TI - Ultrasonographically locating the mental foramen and its soft tissue relations.
AB - OBJECTIVES: This ultrasound-based cross-sectional study aimed to visualize,
locate and compare the position of the mental foramen with regard to its
relationship to various soft tissue landmarks. METHODS: 100 Black and Caucasian
subjects were included. An ultrasound transducer was used to locate the mental
foramina. Distances to various landmarks were measured and compared. RESULTS: All
mental foramina were visualized. The mean soft tissue distance of the entire
group from the mental foramen on the right and left sides, respectively, were as
follows: (a) 3.4 mm [standard deviation (SD) 1.7 mm] and 3.4 mm (SD 1.5 mm)
lateral to a vertical line passing through the chelion; (b) 20.1 mm (SD 2.6 mm)
and 20.1 mm (SD 2.6 mm) distal to a horizontal line bisecting the chelions; (c)
15.1 mm (SD 2.4 mm) and 15.0 mm (SD 2.4 mm) proximal to the inferior border of
the mandible. We found no statistically significant differences between race
groups, between gender group and between age categories with regard to the
horizontal soft tissue distance from a vertical line passing through the chelion
to the mental foramen on the right or left sides. There were statistically
significant (but not clinically significant) differences between race groups and
between gender groups but not between age groups with regard to the vertical soft
tissue distance from a horizontal line bisecting the chelions to the mental
foramen as well as from the inferior border of the mandible to the mental foramen
on both the right and left sides. CONCLUSIONS: This study suggests that
ultrasound is a feasible imaging modality that can be utilized to locate the
mental foramen. Differences in the position of the mental foramen with regard to
various soft tissue landmarks are minor and clinically insignificant.
PMID- 27506297
TI - Reaction of Oxidized Polysialic Acid and a Diaminooxy Linker: Characterization
and Process Optimization Using Nuclear Magnetic Resonance Spectroscopy.
AB - Native polysialic acid (natPSA) is a high-molecular-weight glycan composed of
repeat units of alpha-(2 -> 8) linked N-acetylneuraminic acid (Neu5Ac). Mild
periodate oxidation of PSA selectively targets the end sialic acid ring
containing three adjacent alcohols generating a putative aldehyde, which can be
used, after attachment of a linker molecule, for terminal attachment of PSA to
protein. Previously, we showed that the oxidized PSA (oxoPSA) contained a
hemiacetal at the oxidation site and can react with a linker containing an
aminooxy group in a conjugation reaction to form a stable oxime linkage. Thus,
reagents containing an aminooxy group may be prepared for conjugation of PSA to
the carbohydrate moiety of therapeutic proteins, thereby increasing their half
life. These aminooxy-PSA reagents can selectively react with aldehyde groups
generated by mild NaIO4 oxidation of glycans on the surface of the target
protein. To comprehend the conjugation, unoxidized tetrasialic acid and Neu5Ac
were reacted in model reactions with a diaminooxy linker to define the nuclear
magnetic resonance (NMR) chemical shifts. Based on these data, we were able to
show that, in the case of PSA, the reaction with the linker occurs not only at
the expected oxidized end to form an aldoxime but also at the end distal to the
oxidation to form a ketoxime. We determined that, in aged solutions, both oxoPSA
and PSA aldoxime were hydrolyzed. PSA aldoxime was also shown to disproportionate
to form a dimer (PSA-linker-PSA), which then could react further with the
released linker at one of its PSA termini. Furthermore, NMR was used to monitor
the effects of deliberate process changes so that conditions could be optimized
for attachment of linker at the desired end of the PSA chain, which led to a well
defined product.
PMID- 25060184
TI - Aggressive primary thyroid lymphoma: imaging features of two elderly patients.
AB - We report two cases of aggressive thyroid lymphoma in elderly patients that
presented as large infiltrative thyroid masses with extensive invasion to
adjacent structures including trachea, esophagus, and common carotid artery.
Ultrasonography displayed irregular shaped, heterogeneous hypoechoic mass,
mimicking anaplastic carcinoma. Computed tomography showed heterogeneously
enhancing mass compared to surrounding muscles without calcification and
hemorrhage. After biopsy, the masses were histopathologically diagnosed as
lymphoma. Aggressive primary thyroid lymphoma is rare; therefore, here we report
its image features, with emphasis on ultrasonographic findings, and discuss its
differential diagnosis.
PMID- 27506299
TI - Pancreatic Premalignant Lesions Secrete Tissue Inhibitor of Metalloproteinases-1,
Which Activates Hepatic Stellate Cells Via CD63 Signaling to Create a
Premetastatic Niche in the Liver.
AB - BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) metastasizes to liver
at early stages, making this disease highly lethal. Tissue inhibitor of
metalloproteinases-1 (TIMP1) creates a metastasis-susceptible environment in the
liver. We investigated the role of TIMP1 and its receptor CD63 in metastasis of
early-stage pancreatic tumors using mice and human cell lines and tissue samples.
METHODS: We obtained liver and plasma samples from patients in Germany with
chronic pancreatitis, pancreatic intra-epithelial neoplasia, or PDAC, as well as
hepatic stellate cells (HSCs). We performed studies with Ptf1a+/Cre;Kras+/LSL
G12D;Trp53loxP/loxP (CPK) mice, Pdx-1+/Cre;Kras+/LSL-G12D;Trp53+/LSL-R172H (KPC)
mice, and their respective healthy littermates as control, and Cd63-/- mice with
their wild-type littermates. KPC mice were bred with Timp1-/- mice to produce
KPCxTimp1-/- mice. TIMP1 was overexpressed and CD63 was knocked down in mice
using adenoviral vectors AdTIMP1 or AdshCD63, respectively. Hepatic
susceptibility to metastases was determined after intravenous inoculation of
syngeneic 9801L pancreas carcinoma cells. Pancreata and liver tissues were
collected and analyzed by histology, immunohistochemical, immunoblot, enzyme
linked immunosorbent assay, and quantitative polymerase chain reaction analyses.
We analyzed the effects of TIMP1 overexpression or knockdown and CD63 knockdown
in transduced human primary HSCs and HSC cell lines. RESULTS: Chronic
pancreatitis, pancreatic intra-epithelial neoplasia, and PDAC tissues from
patients expressed higher levels of TIMP1 protein than normal pancreas. The
premalignant pancreatic lesions that developed in KPC and CPK mice expressed
TIMP1 and secreted it into the circulation. In vitro and in vivo, TIMP1 activated
human or mouse HSCs, which required interaction between TIMP1 and CD63 and
signaling via phosphatidylinositol 3-kinase, but not TIMP1 protease inhibitor
activity. This signaling pathway induced expression of endogenous TIMP1. TIMP1
knockdown in HSCs reduced their activation. Cultured TIMP1-activated human and
mouse HSCs began to express stromal-derived factor-1, which induced neutrophil
migration, a marker of the premetastatic niche. Mice with pancreatic intra
epithelial neoplasia-derived systemic increases in TIMP1 developed more liver
metastases after injections of pancreatic cancer cells than mice without
increased levels of TIMP1. This increase in formation of liver metastases from
injected pancreatic cancer cells was not observed in TIMP1 or CD63 knockout mice.
CONCLUSIONS: Expression of TIMP1 is increased in chronic pancreatitis, pancreatic
intra-epithelial neoplasia, and PDAC tissues from patients. TIMP1 signaling via
CD63 leads to activation of HSCs, which create an environment in the liver that
increases its susceptibility to pancreatic tumor cells. Strategies to block TIMP1
signaling via CD63 might be developed to prevent PDAC metastasis to the liver.
PMID- 27506300
TI - Domoic acid disrupts the activity and connectivity of neuronal networks in
organotypic brain slice cultures.
AB - Domoic acid is a neurotoxin produced by algae and is found in seafood during
harmful algal blooms. As a glutamate agonist, domoic acid inappropriately
stimulates excitatory activity in neurons. At high doses, this leads to seizures
and brain lesions, but it is unclear how lower, asymptomatic exposures disrupt
neuronal activity. Domoic acid has been detected in an increasing variety of
species across a greater geographical range than ever before, making it critical
to understand the potential health impacts of low-level exposure on vulnerable
marine mammal and human populations. To determine whether prolonged domoic acid
exposure altered neuronal activity in hippocampal networks, we used a custom-made
512 multi-electrode array with high spatial and temporal resolution to record
extracellular potentials (spikes) in mouse organotypic brain slice cultures. We
identified individual neurons based on spike waveform and location, and measured
the activity and functional connectivity within the neuronal networks of brain
slice cultures. Domoic acid exposure significantly altered neuronal spiking
activity patterns, and increased functional connectivity within exposed cultures,
in the absence of overt cellular or neuronal toxicity. While the overall spiking
activity of neurons in domoic acid-exposed cultures was comparable to controls,
exposed neurons spiked significantly more often in bursts. We also identified a
subset of neurons that were electrophysiologically silenced in exposed cultures,
and putatively identified those neurons as fast-spiking inhibitory neurons. These
results provide evidence that domoic acid affects neuronal activity in the
absence of cytotoxicity, and suggest that neurodevelopmental exposure to domoic
acid may alter neurological function in the absence of clinical symptoms.
PMID- 27506302
TI - C2H4 adsorption on Cu(210), revisited: bonding nature and coverage effects.
AB - With the aid of density functional theory (DFT)-based calculations, we
investigate the adsorption of C2H4 on Cu(210). We found two C2H4 adsorption
sites, viz., the top of the step-edge atom (S) and the long bridge between two
step-edge atoms (SS) of Cu(210). The step-edge atoms on Cu(210) block the
otherwise active terrace sites found on copper surfaces with longer step sizes.
This results in the preference for pi-bonded over di-sigma-bonded C2H4. We also
found two stable C2H4 adsorption orientations on the S- and SS-sites, viz., with
the C2H4 C[double bond, length as m-dash]C bond parallel (fit) and perpendicular
(cross) to [001]. Furthermore, we found that the three peaks observed in previous
temperature programmed desorption (TPD) experiment [Surf. Sci., 2011, 605, 934
940] could be attributed to C2H4 in the S-fit or S-cross, S-fit and S-cross-fit
(S-cross and S-fit configurations that both exist in the same unit cell)
configurations on Cu(210).
PMID- 27506301
TI - A quasi-cyclic RNA nano-scale molecular object constructed using kink turns.
AB - k-Turns are widespread RNA architectural elements that mediate tertiary
interactions. We describe a double-kink-turn motif comprising two inverted k
turns that forms a tight horse-shoe structure that can assemble into a variety of
shapes by coaxial association of helical ends. Using X-ray crystallography we
show that these assemble with two (dumbell), three (triangle) and four units
(square), with or without bound protein, within the crystal lattice. In addition,
exchange of a single basepair can almost double the pore radius or shape of a
molecular assembly. On the basis of this analysis we synthesized a 114 nt self
complementary RNA containing six k-turns. The crystal structure of this species
shows that it forms a quasi-cyclic triangular object. These are randomly disposed
about the three-fold axis in the crystal lattice, generating a circular RNA of
quasi D3 symmetry with a shape reminiscent of that of a cyclohexane molecule in
its chair conformation. This work demonstrates that the k-turn is a powerful
building block in the construction of nano-scale molecular objects, and
illustrates why k-turns are widely used in natural RNA molecules to organize long
range architecture and mediate tertiary contacts.
PMID- 27506303
TI - Sampling effort of periphytic diatoms for bioassessment research using taxonomic
distinctness in marine ecosystems: A case study in coastal waters.
AB - The sampling effort for detecting taxonomic distinctness of periphytic diatom
communities was studied in coastal waters of the Yellow Sea, northern China, from
May to June 2014. Samples with different sizes (microscopy glass slides) were
collected at two depths of 1m and 3m. To obtain the communities with
dissimilarities of <10%, 2 slide replicates were sufficient for sampling at a
depth of 1m, while 4 were required for the those at a depth of 3m. The values of
four taxonomic distinctness indices represented a low sensitivity to sample sizes
over all exposure period ages: at a coefficient of variation of <10%, 2 and 9
slide replicates were required at a depth of 1m and 3m, respectively. We suggest
that the sampling strategy of the diatoms for detecting taxonomic distinctness
might be better at 1m than at a deeper layer in coastal waters.
PMID- 27506304
TI - Experimental study of oil plume stability: Parametric dependences and
optimization.
AB - Oil plume is known to interact with density layer in spilled oil. Previous
studies mainly focused on tracking oil plumes and predicting their impact on
marine environment. Here, simulated experiments are presented that investigated
the conditions inducing the formation of oil plume, focusing especially on the
effects of oil/water volume ratio, oil/dispersant volume rate, ambient
stratification and optimal conditions of oil plume on determining whether a plume
will trap or escape. Scenario simulations showed that OWR influences the
residence time most, dispersants dosage comes second and salinity least. The
optimum residence time starts from 2387s, occurred at approximately condition
(OWR, 0.1, DOR, 25.53% and salinity, 32.38). No change in the relative
distribution under the more scale tank was observed, indicating these provide the
time evolution of the oil plumes.
PMID- 27506305
TI - Phosphate Ions Affect the Water Structure at Functionalized Membrane Surfaces.
AB - Antifouling surfaces improve function, efficiency, and safety in products such as
water filtration membranes, marine vehicle coatings, and medical implants by
resisting protein and biofilm adhesion. Understanding the role of water structure
at these materials in preventing protein adhesion and biofilm formation is
critical to designing more effective coatings. Such fouling experiments are
typically performed under biological conditions using isotonic aqueous buffers.
Previous studies have explored the structure of pure water at a few different
antifouling surfaces, but the effect of electrolytes and ionic strength (I) on
the water structure at antifouling surfaces is not well studied. Here sum
frequency generation (SFG) spectroscopy is used to characterize the interfacial
water structure at poly(ether sulfone) (PES) and two surface-modified PES films
in contact with 0.01 M phosphate buffer with high and low salt (Ionic strength,
I= 0.166 and 0.025 M, respectively). Unmodified PES, commonly used as a
filtration membrane, and modified PES with a hydrophobic alkane (C18) and with a
poly(ethylene glycol) (PEG) were used. In the low ionic strength phosphate
buffer, water was strongly ordered near the surface of the PEG-modified PES film
due to exclusion of phosphate ions and the creation of a surface potential
resulting from charge separation between phosphate anions and sodium cations.
However, in the high ionic strength phosphate buffer, the sodium and potassium
chloride (138 and 3 mM, respectively) in the phosphate buffered saline screened
this charge and substantially reduced water ordering. A much smaller water
ordering and subsequent reduction upon salt addition was observed for the C18
modified PES, and little water structure change was seen for the unmodified PES.
The large difference in water structuring with increasing ionic strength between
widely used phosphate buffer and phosphate buffered saline at the PEG interface
demonstrates the importance of studying antifouling coatings in the same aqueous
environment for which they are designed. These results further suggest that
strong long-range water structuring is limited in high ionic strength
environments, such as within cells, facilitating chemical and biological
reactions and processes.
PMID- 27506307
TI - An unprecedented one-step synthesis of octahedral Cu(ii)-bis(iminoquinone)
complexes and their reactivity with NaBH4.
AB - A new non-innocent ligand, H2L(AP(o-NO2-OPh)), was synthesized. The ligand
H2L(AP(o-NO2-OPh)) reacted with 0.5 equivalents of CuCl2.2H2O and provided the
corresponding mononuclear four-coordinate [Cu(ii)-bis(iminosemiquinone)] complex
(1). Interestingly, the ligand upon reacting with 2 equivalents of CuCl2.2H2O in
the presence of Et3N and air provided the corresponding trans-dichloride-bound
six-coordinate mononuclear Cu(ii)-complex (2) in one step. To extend the validity
of the newly developed one-step synthesis of the trans-dichloride-bound Cu(ii)
bis(iminoquinone) complex using a non-innocent ligand and 2 equivalents of
CuCl2.2H2O, the previously reported non-innocent ligand H2L(AP) was further
examined. Thus the formed trans-dichloride-bound Cu(ii)-bis(iminoquinone) complex
was designated as complex 3. The complexes were characterized by IR, mass, UV
Vis/NIR, X-band EPR, and X-ray single crystal diffraction techniques. Molecular
structure analysis confirmed that in 1 the oxidation state of the coordinating
ligands was [L(ISQ(o-NO2-OPh))](1-), i.e., one-electron oxidized
iminosemiquinone. In 2 and 3.CH2Cl2, both the coordinated-ligands were present in
their two-electron oxidized iminoquinone form. The iminoquinone-complex formation
was found to proceed with the generation of CuCl salt. X-band EPR spectrum
measurement confirmed that both the iminoquinone-complexes were paramagnetic and
the unpaired electron was located at the 3dx(2)-y(2) orbital of Cu(ii) ions. When
the Cu(ii)-bis(iminoquinone) complex 3 was subjected to react with NaBH4 in dry
CH3CN, H2 gas was formed along with the generation of the corresponding Cu(ii)
bis(iminosemiquinone) complex. GC analyses were performed for the identification
of H2 gas.
PMID- 27506308
TI - Commentary to "Determinants of practice patterns in pediatric UTI".
PMID- 27506309
TI - Unexpected reductions in regional cerebral perfusion during prolonged hypoxia.
AB - KEY POINTS: Cognitive performance is impaired by hypoxia despite global cerebral
oxygen delivery and metabolism being maintained. Using arterial spin labelled
(ASL) magnetic resonance imaging, this is the first study to show regional
reductions in cerebral blood flow (CBF) in response to decreased oxygen supply
(hypoxia) at 2 h that increased in area and became more pronounced at 10 h.
Reductions in CBF were seen in brain regions typically associated with the
'default mode' or 'task negative' network. Regional reductions in CBF, and
associated vasoconstriction, within the default mode network in hypoxia is
supported by increased vasodilatation in these regions to a subsequent
hypercapnic (5% CO2 ) challenge. These results suggest an anatomical mechanism
through which hypoxia may cause previously reported deficits in cognitive
performance. ABSTRACT: Hypoxia causes an increase in global cerebral blood flow,
which maintains global cerebral oxygen delivery and metabolism. However,
neurological deficits are abundant under hypoxic conditions. We investigated
regional cerebral microvascular responses to acute (2 h) and prolonged (10 h)
poikilocapnic normobaric hypoxia. We found that 2 h of hypoxia caused an expected
increase in frontal cortical grey matter perfusion but unexpected perfusion
decreases in regions of the brain normally associated with the 'default mode' or
'task negative' network. After 10 h in hypoxia, decreased blood flow to the major
nodes of the default mode network became more pronounced and widespread. The use
of a hypercapnic challenge (5% CO2 ) confirmed that these reductions in cerebral
blood flow from hypoxia were related to vasoconstriction. Our findings
demonstrate steady-state deactivation of the default network under acute hypoxia,
which become more pronounced over time. Moreover, these data provide a unique
insight into the nuanced localized cerebrovascular response to hypoxia that is
not attainable through traditional methods. The observation of reduced perfusion
in the posterior cingulate and cuneal cortex, which are regions assumed to play a
role in declarative and procedural memory, provides an anatomical mechanism
through which hypoxia may cause deficits in working memory.
PMID- 27506310
TI - Treatment discontinuation of oral hypoglycemic agents and healthcare utilization
among patients with diabetes.
AB - AIMS: To investigate the discontinuation of oral antihyperglycemic agents (OHA),
and examine factors associated with OHA discontinuation, and the effect of OHA
discontinuation on glycemic control and healthcare utilization among diabetes
patients prescribed dual OHA therapy. METHODS: We identified 23,612 adult
patients aged >18years with a diagnosis of type 2 diabetes who initiated dual OHA
therapy between 1/1/2005 and 6/30/2010. The date of initiation of the second OHA
was defined as the index date. Discontinuation was defined as a gap >1.5 times
the last days' supply without subsequent reinitiation. RESULTS: Over 24months,
16.9% discontinued 1 OHA and 9.2% discontinued both. Patients who discontinued
were more likely to be female, younger, Black or of Hispanic ethnicity, have more
comorbidities, higher medication co-pays, start both OHAs together, have higher
healthcare utilization before the index date and less likely to use prescription
mail order compared with patients who did not discontinue. In multivariable
regression models, patients who discontinued were more likely to be hospitalized
or have emergency department visits during follow-up. CONCLUSIONS:
Discontinuation of OHAs is common among patients with diabetes and is associated
with several patient factors and increased healthcare utilization. Future
research should further examine reasons for OHA discontinuation.
PMID- 27506311
TI - Development and optimization of psychological stress model in mice using 2 level
full factorial design.
AB - INTRODUCTION: Psychological stress has long been a silent killer, impairing
normal physiological functions and leading to a variety of diseased conditions.
However, the existing animal models for studying psychological stress have been
marred by their inherent limitations warranting further research in their
development and optimization. METHODS: In this study 25 full factorial design was
utilized for the development and optimization of psychological stress model in
mice by applying different stressors viz., slanted cage(X1), restraint(X2), no
bedding(X3), dirty bedding(X4) and isolation(X5) at two time duration levels of
30 and 60min. The development of behavioral changes like depression, anxiety and
anhedonia was taken as criteria for development of stress. These responses were
analyzed using Design Expert 7.1.6. (Stat-Ease, Inc., USA). The maximum effective
responses obtained were taken as a criterion for optimization. The optimized
model was applied to measure the change in serum cortisol level to confirm the
stress development. RESULTS: The statistical data showed that a quadratic model
was fitted to the data obtained. All the factors were found to have a significant
role in the development of stress among which restraint, slanted cage and dirty
bedding were found to be more causal (p<0.05). Serum cortisol level was increased
significantly in the stressed mice of optimized model (p<0.05). DISCUSSION:
Utilizing the magnitude of responses from the quadratic equations, it can be
concluded that slanted cage, restraint and dirty bedding stressors should be
applied for longer duration than other stressors for psychological stress
development in mice. The study could lay a strong platform for the use of quality
by design approach in the development of robust, efficient and resourceful animal
models.
PMID- 27506312
TI - Epidermal growth factor-induced stimulation of proliferation and gene expression
changes in the hypotrichous ciliate, Stylonychia lemnae.
AB - Epidermal growth factor (EGF) induces proliferation of epidermal and epithelial
tissues in mammals. However, the effect of EGF on the single-celled eukaryotes is
not well characterized, especially in the protists. Ciliates, an important group
of protists, are well characterized as both pollution indicators and model
organisms for research. Stylonychia lemnae, is one of the most common free-living
ciliates, widely distributed in ponds, rivers and marshes. Here, we report the
role of EGF on cell proliferation stimulation in S. lemnae. The growth curve of
S. lemnae was established, and the stimulation effect of EGF on the proliferation
of S. lemnae was investigated. Based on the results, potential EGF receptors were
identified in S. lemnae according to the conserved domains and gene expression.
Differential gene expression revealed that EGF-induced genes in other organisms
(e.g. antioxidant) also up-regulated in S. lemnae cells at propagation stages. In
addition, our results showed that EGF could up-regulate the signal transduction
related processes in the decline stage of S. lemnae cells, indicating its
potential function in apoptosis inhibition. In summary, this study reports
findings of the first investigation of EGF effects in hypotrich ciliates, and
establishes an additional system for the study of the molecular mechanisms of EGF
actions in eukaryotic cell division and proliferation.
PMID- 27506313
TI - miR-490-3p inhibits the growth and invasiveness in triple-negative breast cancer
by repressing the expression of TNKS2.
AB - Identification of key genes driving the aggressiveness of triple-negative breast
cancer (TNBC) is important to develop effective therapies. In this study, we
examined the expression and biological roles of microRNA (miR)-490-3p in TNBC.
Our data showed that miR-490-3p-3p was underexpressed in TNBC compared with non
TNBC tissues (P=0.0021). Similarly, this miRNA was expressed at lower levels in
TNBC cell lines than in non-TNBC cell lines. Gain-of-function studies revealed
that miR-490-3p-3p overexpression inhibited cell growth and invasion in both MDA
MB-231 and MDA-MB-436 TNBC cells and impaired tumorigenesis of MDA-MB-231 cells
in nude mice. Mechanistically, we found that miR-490-3p negatively regulated the
expression of tankyrase 2 (TNKS2) via binding to its 3'-untranslated region and
then blocked the activation of beta-catenin signaling. Importantly,
overexpression of a miR-490-3p-resistant form of TNKS2 reversed miR-490-3p
mediated suppression of TNBC cell proliferation and invasion. Knockdown of TNKS2
via small interfering RNA technology was found to mimic the suppressive activity
of miR-490-3p in MDA-MB-231 cells. Taken together, miR-490-3p is downregulated in
TNBC and plays a suppressive role in cancer cell proliferation, invasion, and
tumorigenesis. The tumor suppressive activity of miR-490-3p is largely mediated
through downregulation of TNKS2 and inactivation of beta-catenin signaling. Thus,
miR-490-3p may represent a potential therapeutic target for TNBC.
PMID- 27506314
TI - Systematic analyses of key genes and pathways in the development of invasive
breast cancer.
AB - BACKGROUND: Ductal carcinoma in situ (DCIS) is a common type of non-invasive
breast cancer and can sometimes progress into invasive breast cancer (IBC).
Identification of the critical genes and biological processes specifically and/or
commonly changed in DCIS or IBC can help us understand more about breast cancer
development and provide more critical targets and signal transduction pathways
for the diagnosis and treatments for breast cancer patients. AIM AND METHODS: We
aimed to gain more understanding about the whole process of IBC development,
especially in the early stage. Here we systematically analyzed an online breast
cancer patient database to identify those significantly changed genes and
biological processes in epithelium from normal stage to DCIS stage or from DCIS
stage to IBC stage. RESULTS: 344 specific genes, such as FN1, AURKA and HSPA8,
were found to be significantly changed (both upregulated and downregulated) in
DCIS group in comparison with normal tissue group, which represents the gene
profile changes in early stage of breast cancer development. Meanwhile, 304
specific genes were significantly changed (both upregulated and downregulated) in
IBC group in comparison with normal tissue group, which represents the gene
profile changes in late stage of breast cancer development. Importantly, seven
genes were identified to have consistent changes in both early stage and late
stage, indicating they might play "driving" roles in the breast cancer
development. Of these 7 genes, 5 have been shown to be involved in breast cancer
progression by previous studies, which demonstrates the validity of our analyses.
Notably, DNAPTP3 was identified for the first time to play an oncogenic role in
breast cancer development. In the GO term analyses, cell cycle genes was found to
play more important roles in the early stage while biological adhesion was
indicated to be more specifically involved in late stage of breast cancer
development. SIGNIFICANCE: Our systematic analyses provide better understanding
of the unique gene profiles and biological processes during the breast cancer
development and identify more potentially important targets for future studies,
such as DNAPTP3.
PMID- 27506316
TI - Determination of metabolic profile of novel triethylamine containing thiophene
S006-830 in rat, rabbit, dog and human liver microsomes.
PMID- 27506315
TI - Transcriptional regulation of the canine carbonyl reductase 1 gene (cbr1) by the
specificity protein 1 (Sp1).
AB - The clinical use of anthracyclines to treat various canine cancers is limited by
the development of cardiotoxicity. The intra-cardiac synthesis of anthracycline C
13 alcohol metabolites (e.g. daunorubicinol) contributes to the development of
cardiotoxicity. Canine carbonyl reductase 1 (cbr1) catalyzes the reduction of
daunorubicin into daunorubicinol. Recent mapping of the cbr1 locus by sequencing
DNA samples from dogs from various breeds revealed a cluster of conserved motifs
for the transcription factor Sp1 in the putative promoter region of cbr1. We
hypothesized that the variable number of Sp1 motifs could impact the
transcription of canine cbr1. In this study, we report the functional
characterization of the canine cbr1 promoter. Experiments with reporter
constructs and chromatin immunoprecipitation show that cbr1 transcription depends
on the binding of Sp1 to the proximal promoter. Site-directed mutagenesis
experiments suggest that the variable number of Sp1 motifs impacts the
transcription of canine cbr1. Inhibition of Sp1-DNA binding decreased canine cbr1
mRNA levels by 54% in comparison to controls, and also decreased enzymatic
carbonyl reductase activity for the substrates daunorubicin (16%) and menadione
(23%). The transactivation of Sp1 increased the expression of cbr1 mRNA (67%),
and increased carbonyl reductase activity for daunorubicin (35%) and menadione
(27%). These data suggest that the variable number of Sp1 motifs in the canine
cbr1 promoter may impact the pharmacodynamics of anthracyclines in canine cancer
patients.
PMID- 27506317
TI - Improvement in symptoms of obstructive sleep apnoea in children following
tonsillectomy versus tonsillotomy: a systematic review and meta-analysis.
AB - BACKGROUND: Tonsillotomy (or intracapsular tonsillectomy) is a modern technique
which is seen by some as potentially superior to traditional (extracapsular)
tonsillectomy for the removal of tonsillar tissue to treat obstructive sleep
apnoea in children. It has been suggested that peri-operative pain and
haemorrhage and postoperative haemorrhage are reduced with the tonsillotomy
technique. However, no systematic reviews have been carried out to assess its
efficacy in treating obstructive sleep apnoea compared to tonsillectomy.
OBJECTIVE OF REVIEW: To assess whether subjective improvement in symptoms of
obstructive sleep apnoea following tonsillotomy is comparable to that following
tonsillectomy, measured using a standardised questionnaire, the Obstructive sleep
apnoea-18 (OSA-18) tool. TYPE OF REVIEW: Systematic review of the literature and
meta-analysis. SEARCH STRATEGY: PubMed (MEDLINE), followed by Ovid (MEDLINE),
Cochrane Database of Systematic Reviews, American College of Physicians Journal
Club, and the British Medical Journal were searched for articles published in
English between 1995 and 2015 inclusive. EVALUATION METHOD: Literature search,
systematic review and meta-analysis. Studies examining improvement in mean OSA-18
score following tonsillotomy, improvement in mean OSA-18 score following
tonsillectomy, and examining both were selected, examined and used for meta
analysis. Studies with and without concurrent adenoidectomy were included.
RESULTS: Four studies examining tonsillotomy and 16 studies examining
tonsillectomy were included in the analysis. Using a random effects model, the
pooled improvement in OSA-18 score for tonsillotomy was 2.46 (95% CI 1.92-2.99),
and for tonsillectomy, it was 2.10 (95% CI 1.91-2.30). There was no significant
difference between the methods. CONCLUSION: That there is no significant
difference in subjective outcome between tonsillotomy and tonsillectomy may
support wider use of tonsillotomy over tonsillectomy for the treatment of
obstructive sleep apnoea in children.
PMID- 27506318
TI - Introducing the Wiley Transplant Peer Review Network.
PMID- 27506319
TI - Erratum.
PMID- 27506320
TI - Interaction between migration behaviour and estuarine mortality in cultivated
Atlantic salmon Salmo salar smolts.
AB - Migration behaviour and estuarine mortality of cultivated Atlantic salmon Salmo
salar smolts in a 16 km long estuary were studied using two methods: (1) acoustic
telemetry and (2) group tagging in combination with trap nets. Progression rates
of surviving individuals through the estuary were relatively slow using both
methods [0.38 LT (total length) s-1 v. 0.25 LT s-1 ]. In 2012, the progression
rate was slow from the river to the estuary (0.55 LT s-1 ) and the first part of
the estuary (0.31 LT s-1 ), but increased thereafter (1.45-2.21 LT s-1 ). In
2013, the progression rate was fast from the river to the estuary (4.31 LT s-1 )
but was slower thereafter (0.18-0.91 LT s-1 ). Survival to the fjord was higher
in 2012 (47%) compared to 2013 (6%). Fast moving individuals were more likely to
migrate successfully through the estuary compared to slower moving individuals.
Adult recapture of coded-wire-tagged S. salar was generally low (0.00-0.04%).
Mortality hot spots were related to topographically distinct areas such as the
river outlet (in 2012) or the sill separating the estuary and the fjord (in
2013). At the sill, an aggregation of cod Gadus morhua predating on cultivated
smolts was identified. The results indicate that slow progression rates through
the estuary decreases the likelihood of smolts being detected outside the
estuary. The highly stochastic and site-specific mortality patterns observed in
this study highlight the complexity in extrapolating mortality patterns of single
release groups to the entire smolt run of wild S. salar.
PMID- 27506321
TI - Spectral Analysis of Baseline Electrocardiogram During Atrial Fibrillation
Predicts Response to Antiarrhythmic Drug Therapy in Patients With Persistent
Atrial Fibrillation.
AB - BACKGROUND: We evaluated the ability of spectral analysis of the baseline ECG
during atrial fibrillation (AF) to predict the response of persistent AF to
antiarrhythmic drug therapy. METHODS: Patients with persistent AF who were
admitted for dofetilide loading were prospectively enrolled in the study. Atrial
activity was extracted from the ECG using an Independent Component Analysis
method and then subjected to a Modified Periodogram. The regularity index was
computed as the ratio of the power in the dominant frequency and all its
harmonics to the total power in the spectrum. Patients were followed at 1 month,
3 months and every 3 months thereafter. RESULTS: Of 28 patients enrolled in the
study, 14 (50%) converted acutely to sinus rhythm during the 3-day hospital
loading period. The clinical and echocardiographic characteristics of patients
with and without acute pharmacologic conversion were similar. The regularity
index was significantly higher in those who converted to sinus rhythm compared to
those who did not (0.71 +/- 0.20 vs. 0.38 +/- 0.13, respectively; P < 0.0001). A
regularity index >=0.44 had a 79% sensitivity and 93% specificity to predict
acute conversion and was associated with a nearly 5-fold increase in the acute
conversion rate (odds ratio = 4.89; 95% confidence interval 1.74-13.75; P =
0.003). The regularity index was the only independent predictor of acute
conversion. Neither acute conversion, nor the regularity index predicted sinus
rhythm maintenance, after a median follow-up of 10 months. CONCLUSION: Increased
regularity index predicts acute conversion of persistent AF during dofetilide
loading, but does not predict long-term sinus rhythm maintenance.
PMID- 27506322
TI - Relationship between the cranial base and the mandible in artificially deformed
skulls.
AB - OBJECTIVES: There is controversy regarding the relationship between mandibular
position and alterations of the cranial base that provoke a more anterior
location of the glenoid fossa. Artificially deformed skulls display marked
alterations of the cranial base. This study evaluates mandibular changes as
function of the morphology of the cranial base in these skulls. MATERIAL AND
METHODS: A geometric morphometric study was performed on lateral cephalometric X
rays of three groups of skulls: 32 with anteroposterior deformity, 17 with
circumferential deformity and 39 with no apparent deformity. RESULTS: In
artificially deformed skulls, the cranial base was deformed causing the
mandibular condyle to be in a more anterior position. There was a complete
remodelling of the mandible involving narrowing and elongation of the mandibular
ramus, rotation of the corpus of the mandible and increased vertical height of
the symphysis. Forward displacement did not occur. Integration between mandible
and cranial base is not altered by deformation of the skull. CONCLUSIONS:
Deformity of the cranial vault exerts an influence on the mandible, supporting
the theory of modular units in complete integration. This also supports the
theory that mandibular prognathism is a multifactorial result and not a direct
effect of displacement of the cranial base.
PMID- 27506323
TI - Short-term storage of salmonids semen in a sodium alginate-based extender.
AB - Short-term storage of semen is a useful strategy for preservation of fish
spermatozoa. However, there is a significantly decrease on sperm function mainly
due to oxidative stress. In this way, sodium alginate plays an important role as
free radical scavenger compound. Accordingly, the aim of our study was to analyse
the effect of a sodium alginate-based extender on sperm function in the short
term storage of salmonids semen. Samples of Salmo salar, Oncorhynchus kisutch,
and Oncorhynchus mykiss were stored in Storfish(r) (Ext-C) and Storfish(r)
supplemented with sodium alginate (Ext-A) during 10 days at 4 degrees C. After
storage, motility, viability, mitochondrial membrane potential (DeltaPsimit),
superoxide anion (O2- ) level and DNA fragmentation (DNA Frag) were assessed. Ext
A had positive effect in preservation of sperm motility, viability, DeltaPsimit,
O2- level and DNA integrity in the three species analysed compared to control
samples. In Ext-A, the spermatozoa of S. salar and O. mykiss showed significantly
higher motility, viability and DeltaPsimit than O. kisutch. However, O. kisutch
and O. mykiss had significantly lower O2- level than S. salar, and DNA
fragmentation in O. kisutch and S. salar was significantly lower than in samples
of O. mykiss (p < 0.05). Dilution of salmonids semen in a sodium alginate-based
extender is effective for protecting sperm quality during 10 days of short-term
storage.
PMID- 27506324
TI - Women with intellectual disability are at a higher risk of adverse maternal and
offspring outcomes.
PMID- 27506325
TI - Thermally induced recrystallization of MAPbI3 perovskite under methylamine
atmosphere: an approach to fabricating large uniform crystalline grains.
AB - A liquid to solid phase transition of methylammonium lead triiodide (MAPbI3)
under methylamine (MA) atmosphere at elevated temperatures was discovered, and
used to form high quality and uniform thin films containing large, low defect
crystal grains tens of microns in size.
PMID- 27506326
TI - Effects of intra-operative maintenance of general anaesthesia with propofol on
postoperative pain outcomes - a systematic review and meta-analysis.
AB - Propofol is used both for induction and maintenance of anaesthesia. Recent
evidence shows that propofol has analgesic properties. This meta-analysis
evaluated differences in postoperative analgesia between general anaesthetic
maintenance with intravenous propofol and inhalational anaesthetics. Fourteen
trials met inclusion criteria and were included. Our outcomes were pain scores 2
and 24 h after surgery. No significant difference in pain scores was found at 2 h
after surgery (Hedge's g (95% CI) -0.120 (-0.415-0.175) (p = 0.425). Propofol was
associated with a statistically significant, albeit marginal, reduction in pain
scores 24 h after surgery (Hedge's g (95% CI) -0.134 (-0.248 to -0.021) (p =
0.021). Data were insufficient to allow a meaningful analysis regarding 24-h
morphine-equivalent consumption. Propofol was associated with reduced
postoperative nausea and vomiting (relative risk (95%CI) 0.446 (0.304-0.656) (p <
0.0001). In conclusion, this meta-analysis suggests that propofol improves
postoperative analgesia compared with inhalational anaesthesia 24 h after
surgery, with a lower incidence of nausea and vomiting.
PMID- 27506327
TI - Evaluation of successful aging among older people in China: Results from China
health and retirement longitudinal study.
AB - AIM: China faces a "time-bomb" of the aging population. Successful aging has long
been a goal in the field of gerontology. The present study aimed to evaluate
successful aging among Chinese older adults. METHODS: Data on a total of 7102
people in the China Health and Retirement Study aged >=60 years were analyzed in
the present study. Successful aging is defined by the model of Rowe and Kahn
including the following five indicators: "no major diseases," "no disability,"
"high cognitive functioning," "high physical functioning" and "active engagement
with life." Using logistic regression analysis, crude and adjusted odds ratios
with 95% confidence intervals were calculated to evaluate the relationship
between sociodemographic parameters and successful aging. RESULTS: The prevalence
of successful aging was 13.2% among Chinese older people. The percentage of older
people with the five indicators, "no major diseases," "no disability," "high
cognitive functioning," "high physical functioning," and "active engagement with
life" was 41.7%, 92.1%, 54.2%, 70.2% and 46.0%, respectively. Multiple logistic
regression showed people who had received education of high/vocational school or
above had significantly greater odds of successful aging compared with those with
less than primary school education (P < 0.05). The effect of education to college
level or above on cognitive functioning was 2.51-fold higher in women than men (P
= 0.006). Older people from a non-agricultural Hukou had 1.85-fold higher odds of
successful aging than those from an agricultural Hukou. Older people living in
the central, northeast or western regions had lower odds of successful aging
relative to those living in the east coast region (0.72, 0.72 and 0.56,
respectively). CONCLUSIONS: The prevalence of successful aging is low among
Chinese older people, and is affected by sociodemographic factors, such as
education, Hukou and regions. Geriatr Gerontol Int 2017; 17: 1183-1190.
PMID- 27506328
TI - Comparison of models for genetic evaluation of number of inseminations to
conception in Danish Holstein cows.
AB - Number of inseminations to conception (NINS), an important fertility trait,
requires appropriate approaches for genetic evaluation due to its non-normal
distribution and censoring records. In this study, we analyzed NINS in 474 837
Danish Holstein cows at their first lactation by using seven models which deal
with the categorical phenotypes and censored records in different manners,
further assessed these models with regard to stability, lack of bias and accuracy
of prediction. The estimated heritability from four models based on original NINS
specified as a linear Gaussian model, categorical threshold model, threshold
linear model and survival model were similar (0.031-0.037). While for the other
three models based on the binary response derived from NINS, referred as
threshold model (TM), logistic and probit models (LOGM and PROM), the
heritability were estimated as 0.027, 0.063 and 0.027, respectively. The model
comparison concluded that different models could lead to slightly different sire
rankings in terms of breeding values; a more complicated model led to less
stability of prediction; the models based on the binary response derived from
NINS (TM, LOGM and PROM) had slightly better performances in terms of unbiased
and accurate prediction of breeding values.
PMID- 27506329
TI - Ancient DNA reveals differences in behaviour and sociality between brown bears
and extinct cave bears.
AB - Ancient DNA studies have revolutionized the study of extinct species and
populations, providing insights on phylogeny, phylogeography, admixture and
demographic history. However, inferences on behaviour and sociality have been far
less frequent. Here, we investigate the complete mitochondrial genomes of extinct
Late Pleistocene cave bears and middle Holocene brown bears that each inhabited
multiple geographically proximate caves in northern Spain. In cave bears, we find
that, although most caves were occupied simultaneously, each cave almost
exclusively contains a unique lineage of closely related haplotypes. This
remarkable pattern suggests extreme fidelity to their birth site in cave bears,
best described as homing behaviour, and that cave bears formed stable maternal
social groups at least for hibernation. In contrast, brown bears do not show any
strong association of mitochondrial lineage and cave, suggesting that these two
closely related species differed in aspects of their behaviour and sociality.
This difference is likely to have contributed to cave bear extinction, which
occurred at a time in which competition for caves between bears and humans was
likely intense and the ability to rapidly colonize new hibernation sites would
have been crucial for the survival of a species so dependent on caves for
hibernation as cave bears. Our study demonstrates the potential of ancient DNA to
uncover patterns of behaviour and sociality in ancient species and populations,
even those that went extinct many tens of thousands of years ago.
PMID- 27506331
TI - The impact of delayed biliary decompression and anti-microbial therapy in 260
patients with cholangitis-associated septic shock.
AB - BACKGROUND: Cholangitis-associated septic shock carries significant mortality.
There is uncertainty regarding the most appropriate time to achieve biliary
decompression. AIM: To determine whether the timing of biliary decompression and
anti-microbial therapy affect the survival in cholangitis patients with septic
shock. METHODS: Nested retrospective cohort study of all cholangitis-associated
septic shock patients (hypotension requiring vasopressors) from an international,
multi-centre database between 1996 and 2011. RESULTS: Among 260 patients (mean
age 69 years, 57% male), overall mortality was 37%. Compared to nonsurvivors (n =
96), survivors (n = 164) had lower mean admission Acute Physiology And Chronic
Health Evaluation (APACHE) II (22 vs. 28, P < 0.001) and lower median serum
lactate on admission (3.4 vs. 4.6 mmol/L, P < 0.001). Survivors were more likely
to receive appropriate anti-microbial therapy earlier (median 2.6 vs. 6.8 h from
shock, P < 0.001). Survivors were also more likely to undergo successful biliary
decompression earlier (median 8.8 vs. 22 h, P < 0.001). After adjusting for co
variates, APACHE II (odds ratio, OR 1.21 per increment (1.11-1.32), time delay to
appropriate anti-microbial therapy [OR 1.15 per hour (1.07-1.25)] and delayed
biliary decompression >12 h [OR 3.40 (1.12-10.31)] were all significantly
associated with increased mortality (P < 0.04 for all; c-statistic 0.896).
CONCLUSIONS: Patients with septic shock secondary to acute cholangitis have
significant mortality. Endoscopic biliary decompression >12 h after the onset of
shock and delayed receipt of appropriate anti-microbial therapy were both
significantly associated with adverse hospital outcome. This might suggest that
early initiation of anti-microbial therapy and urgent biliary decompression
(within 12 h) could potentially improve outcomes in this high-risk patient
population.
PMID- 27506330
TI - Pauci-immune glomerulonephritis in a captive chimpanzee (Pan troglodytes), and a
review of spontaneous cases in animals.
AB - BACKGROUND: Crescentic glomeruli are the hallmark finding in rapidly progressive
glomerulonephritis (RPGN) and are characterized by disruption and proliferation
of the glomerular capsule and an influx of cells into Bowman's space. Pauci
immune-type RPGN is identified by a lack of immunoglobulins and immune complexes
in the glomerular basement membrane. METHODS: Complete necropsy and histology
were performed on the affected chimpanzee. Electron microscopy was performed on
kidney sections. A search of the literature was performed to identify spontaneous
RPGN in animals. RESULTS: We report a case of crescentic glomerulonephritis of
the pauci-immune-type in a hepatitis C virus-infected 28-year-old male chimpanzee
(Pan troglodytes) who was humanely euthanized for a cardiac-related decline in
health. CONCLUSION: To our knowledge, this is the first report describing pauci
immune crescentic glomerulonephritis in a non-human primate.
PMID- 27506332
TI - Echocardiographic Evaluation of Hemodynamic Changes in Left-Sided Heart Valves in
Pregnant Women With Valvular Heart Disease.
AB - Physiologic changes during pregnancy can deteriorate or improve patients'
hemodynamic status in the setting of valvular heart disease. There are sparse
data regarding the effect of pregnancy on valve hemodynamics in normal pregnant
women with known valvular heart disease. In a prospective study from July 2014 to
January 2016, a total of 52 normal pregnant women who had mitral stenosis, aortic
stenosis, or a history of mitral valve or aortic valve replacements were
assessed. All patients underwent echocardiographic examinations and hemodynamic
parameters were measured for both the mitral valve and aortic valve at first,
second, and third trimesters. The parameters included mean gradient, peak
gradient, mean gradient/heart rate, peak gradient/heart rate, pressure halftime,
dimensionless velocity index, and valve area. Although most hemodynamic
parameters (i.e., mean gradient, peak gradient, mean gradient/heart rate, and
peak gradient/heart rate) increased approximately 50% from first to second
trimester and first to third trimester (p <0.05) but those remained stable at
third compared with second trimester (p >0.05). The ratio of changes between
trimesters for valve area and dimensionless velocity index were comparable. No
clinical decompensations were observed except for 3 and 7 cases of deterioration
to functional class II at second and third trimesters, respectively. In
conclusion, during a full-term and uncomplicated pregnancy, mitral and aortic
valve gradients increase without significant changes in valve area that are more
marked between the second and first trimester than between the third and second
trimester.
PMID- 27506333
TI - Identification of distinctive molecular traits that are characteristic of the
phylum "Deinococcus-Thermus" and distinguish its main constituent groups.
AB - The phylum "Deinococcus-Thermus" contains two heavily researched groups of
extremophilic bacteria: the highly radioresistant order Deinococcales and the
thermophilic order Thermales. Very few characteristics are known that are
uniquely shared by members of the phylum "Deinococcus-Thermus". Comprehensive
phylogenetic and comparative analyses of >65 "Deinococcus-Thermus" genomes
reported here have identified numerous molecular signatures in the forms of
conserved signature insertions/deletions (CSIs) and conserved signature proteins
(CSPs), which provide distinguishing characteristics of the phylum "Deinococcus
Thermus" and its main groups. We have identified 58 unique CSIs and 155 unique
CSPs that delineate different phylogenetic groups within the phylum. Of these
identified traits, 24 CSIs and 29 CSPs are characteristic of the phylum
"Deinococcus-Thermus" and they provide novel and reliable means to
circumscribe/describe this phylum. An additional 3 CSIs and 3 CSPs are
characteristic of the order Deinococcales, and 6 CSIs and 51 CSPs are
characteristic of the order Thermales. The remaining 25 CSIs and 72 CSPs
identified in this study are distinctive traits of genus level groups within the
phylum "Deinococcus-Thermus". The molecular characteristics identified in this
work provide novel and independent support for the common ancestry of the members
of the phylum "Deinococcus-Thermus" and provide a new means to distinguish the
main constituent clades of the phylum. Additionally, the CSIs and CSPs identified
in this work may play a role in the unique extremophilic adaptations of the
members of this phylum and further functional analyses of these characteristics
could provide novel biochemical insights into the unique adaptations found within
the phylum "Deinococcus-Thermus".
PMID- 27506334
TI - Impact of androgen-deprivation therapy on the outcome of dose-escalation prostate
cancer radiotherapy without elective pelvic irradiation.
AB - The benefit of androgen-deprivation therapy (ADT) in combination with dose
escalated radiotherapy (DERT) for localized prostate cancer has not been
determined in randomized studies. In this study, the benefit of ADT was assessed
in patients uniformly treated with dose-escalated intensity-modulated radiation
therapy (IMRT) to the prostate and seminal vesicles but not pelvis. In all, 419
patients with localized prostate adenocarcinoma underwent definitive IMRT
(cumulative dose 78 Gy), with 32.6%, 33.1%, 32.1%, and 2.1% having T1 through T4
disease, respectively, and 51.2% having high-risk disease. ADT was given to 76.1%
of patients. With a median follow-up of 60 months, 5-year biochemical failure
free, disease-free, and overall survival rates were 87%, 86%, and 87%,
respectively. T stage was an independent predictor of all three rates. Five-year
pelvic nodal recurrence rate was 2.9%. ADT improved biochemical failure-free and
disease-free survival but not overall survival. ADT showed benefit in high-risk
disease but not intermediate-risk disease. Late gastrointestinal and
genitourinary toxicities >= grade 2 occurred in 11.0% and 6.7%, respectively. In
conclusion, DERT with 78 Gy yields good disease control and low rate of pelvic
nodal recurrence. ADT improves disease-free survival in patients with high-risk
but not intermediate-risk disease.
PMID- 27506335
TI - Quantity versus quality: the sperm war.
PMID- 27506336
TI - Duodenal metastases from sarcomatoid renal cell carcinoma: Case report.
PMID- 27506337
TI - A novel 384-multiwell microelectrode array for the impedimetric monitoring of Tau
protein induced neurodegenerative processes.
AB - Over the last decades, countless bioelectronic monitoring systems were developed
for the analysis of cells as well as complex tissues. Most studies addressed the
sensitivity and specificity of the bioelectronic detection method in comparison
to classical molecular biological assays. In contrast, the up scaling as a
prerequisite for the practical application of these novel bioelectronic
monitoring systems is mostly only discussed theoretically. In this context, we
developed a novel 384-multiwell microelectrode array (MMEA) based measurement
system for the sensitive label-free real-time monitoring of neurodegenerative
processes by impedance spectroscopy. With respect to the needs of productive
screening systems for robust and reproducible measurements on high numbers of
plates, we focused on reducing the critical contacting of more than 400
electrodes for a 384-MMEA. Therefore, we introduced an on top array of immersive
counter electrodes that are individually addressed by a multiplexer and connected
all measurement electrodes on the 384-MMEA to a single contact point. More
strikingly, our novel approach provided a comparable signal stability and
sensitivity similar to an array with integrated counter electrodes. Next, we
optimized a SH-SY5Y cell based tauopathy model by introducing a novel 5-fold Tau
mutation eliminating the need of artificial tauopathy induction. In combination
with our novel 384-MMEA based measurement system, the concentration and time
dependent neuroregenerative effect of the kinase inhibitor SRN-003-556 could be
quantitatively monitored. Thus, our novel screening system could be a useful tool
to identify and develop potential novel therapeutics in the field of Tau-related
neurodegenerative diseases.
PMID- 27506338
TI - Organic-resistant screen-printed graphitic electrodes: Application to on-site
monitoring of liquid fuels.
AB - This work presents the potential application of organic-resistant screen-printed
graphitic electrodes (SPGEs) for fuel analysis. The required analysis of the
antioxidant 2,6-di-tert-butylphenol (2,6-DTBP) in biodiesel and jet fuel is
demonstrated as a proof-of-concept. The screen-printing of graphite, Ag/AgCl and
insulator inks on a polyester substrate (250 MUm thickness) resulted in SPGEs
highly compatible with liquid fuels. SPGEs were placed on a batch-injection
analysis (BIA) cell, which was filled with a hydroethanolic solution containing
99% v/v ethanol and 0.1 mol L(-1) HClO4 (electrolyte). An electronic micropipette
was connected to the cell to perform injections (100 MUL) of sample or standard
solutions. Over 200 injections can be injected continuously without replacing
electrolyte and SPGE strip. Amperometric detection (+1.1 V vs. Ag/AgCl) of 2,6
DTBP provided fast (around 8 s) and precise (RSD = 0.7%, n = 12) determinations
using an external calibration curve. The method was applied for the analysis of
biodiesel and aviation jet fuel samples and comparable results with liquid and
gas chromatographic analyses, typically required for biodiesel and jet fuel
samples, were obtained. Hence, these SPGE strips are completely compatible with
organic samples and their combination with the BIA cell shows great promise for
routine and portable analysis of fuels and other organic liquid samples without
requiring sophisticated sample treatments.
PMID- 27506339
TI - Magnetic ionic liquids in analytical chemistry: A review.
AB - Magnetic ionic liquids (MILs) have recently generated a cascade of innovative
applications in numerous areas of analytical chemistry. By incorporating a
paramagnetic component within the cation or anion, MILs exhibit a strong response
toward external magnetic fields. Careful design of the MIL structure has yielded
magnetoactive compounds with unique physicochemical properties including high
magnetic moments, enhanced hydrophobicity, and the ability to solvate a broad
range of molecules. The structural tunability and paramagnetic properties of MILs
have enabled magnet-based technologies that can easily be added to the analytical
method workflow, complement needed extraction requirements, or target specific
analytes. This review highlights the application of MILs in analytical chemistry
and examines the important structural features of MILs that largely influence
their physicochemical and magnetic properties.
PMID- 27506340
TI - The management and exploitation of naturally light-emitting bacteria as a
flexible analytical tool: A tutorial.
AB - Conventional detection of toxic contaminants on surfaces, in food, and in the
environment takes time. Current analytical approaches to chemical detection can
be of limited utility due to long detection times, high costs, and the need for a
laboratory and trained personnel. A non-specific but easy, rapid, and inexpensive
screening test can be useful to quickly classify a specimen as toxic or non
toxic, so prompt appropriate measures can be taken, exactly where required. The
bioluminescent bacteria-based tests meet all these characteristics.
Bioluminescence methods are extremely attractive because of their high
sensitivity, speed, ease of implementation, and statistical significance. They
are usually sensitive enough to detect the majority of pollutants toxic to humans
and mammals. This tutorial provides practical guidelines for isolating,
cultivating, and exploiting marine bioluminescent bacteria as a simple and
versatile analytical tool. Although mostly applied for aqueous phase sample and
organic extracts, the test can also be conducted directly on soil and sediment
samples so as to reflect the true toxicity due to the bioavailability fraction.
Because tests can be performed with freeze-dried cell preparations, they could
make a major contribution to field screening activity. They can be easily
conducted in a mobile environmental laboratory and may be adaptable to
miniaturized field instruments and field test kits.
PMID- 27506341
TI - A novel photoelectrochemical biosensor for protein kinase activity assay based on
phosphorylated graphite-like carbon nitride.
AB - Protein kinases are general and significant regulators in the cell signaling
pathway, and it is still greatly desired to achieve simple and quick kinase
detection. Herein, we develop a simple and sensitive photoelectrochemical
strategy for the detection of protein kinase activity based on the bond between
phosphorylated peptide and phosphorylated graphite-like carbon nitride (P-g-C3N4)
conjugates triggered by Zr(4+) ion coordination. Under optimal conditions, the
increased photocurrent is proportional to the protein kinase A (PKA)
concentration ranging from 0.05 to 50 U/mL with a detection limit of 0.077 U/mL.
Moreover, this photoelectrochemical assay can be also applied to quantitative
analysis of kinase inhibition. The results indicated that the IC50 value
(inhibitor concentration producing 50% inhibitor) for ellagic acid was 9.1 MUM.
Moreover, the developed method is further applied to detect PKA activity in real
samples, which contains serum from healthy person and gastric cancer patients and
breast tissue from healthy person and breast cancer patients. Therefore, the
established protocol provides a new and simple tool for assay of kinase activity
and its inhibitors with low cost and high sensitivity.
PMID- 27506342
TI - Phosphomolybdic acid functionalized graphene loading copper nanoparticles
modified electrodes for non-enzymatic electrochemical sensing of glucose.
AB - A sensitive non-enzymatic glucose electrochemical biosensor (Cu/PMo12-GR/GCE) was
developed based on the combination of copper nanoparticles (CuNPs) and
phosphomolybdic acid functionalized graphene (PMo12-GR). PMo12-GR films were
modified on the surface of glassy carbon electrode (GCE) through electrostatic
self-assembly with the aid of poly diallyl dimethyl ammonium chloride (PDDA).
Then CuNPs were successfully decorated onto the PMo12-GR modified GCE through
electrodeposition. The morphology of Cu/PMo12-GR/GCE was characterized by
scanning electron microscope (SEM). Cyclic voltammetry (CV) and chronoamperometry
were used to investigate the electrochemical performances of the biosensor. The
results indicated that the modified electrode displayed a synergistic effect of
PMo12-GR sheets and CuNPs towards the electro-oxidation of glucose in the
alkaline solution. At the optimal detection potential of 0.50 V, the response
towards glucose presented a linear response ranging from 0.10 MUM to 1.0 mM with
a detection limit of 3.0 * 10(-2) MUM (S/N = 3). In addition, Cu/PMo12-GR/GCE
possessed a high selectivity, good reproducibility, excellent stability and
acceptable recovery, which indicating the potential application in clinical
field.
PMID- 27506343
TI - Ultrasensitive electrochemical biosensor for specific detection of DNA based on
molecular beacon mediated circular strand displacement polymerization and
hyperbranched rolling circle amplification.
AB - Using a cascade signal amplification strategy, an ultrasensitive electrochemical
biosensor for specific detection of DNA based on molecular beacon (MB) mediated
circular strand displacement polymerization (CSDP) and hyperbranched rolling
circle amplification (HRCA) was proposed. The hybridization of MB probe to target
DNA resulted in a conformational change of the MB and triggered the CSDP in the
presence of bio-primer and Klenow fragment (KF exo(-)), leading to multiple
biotin-tagged DNA duplex. Furthermore, the HRCA was implemented to product
amounts of double-stranded DNA (ds-DNA) fragments using phi29 DNA polymerase via
biotin-streptavidin interaction. After the product of HRCA binded numerous
biotinylated detection probes, an ultrasensitive electrochemical readout by
further employing the streptavidin-alkaline phosphatase. The proposed biosensor
exhibited excellent detection sensitivity and specificity with a log-linear
response to target DNA from 0.01 fM to 10 pM as low as 8.9 aM. The proposed
method allowed DNA detection with simplicity, rapidness, low cost and high
specificity, which might have the potential for application in clinical molecular
diagnostics and environmental monitoring.
PMID- 27506344
TI - Amplified electrochemical detection of nucleic acid hybridization via selective
preconcentration of unmodified gold nanoparticles.
AB - The common drawback of optical methods for rapid detection of nucleic acid by
exploiting the differential affinity of single-/double-stranded nucleic acids for
unmodified gold nanoparticles (AuNPs) is its relatively low sensitivity. In this
article, on the basis of selective preconcentration of AuNPs unprotected by
single-stranded DNA (ssDNA) binding, a novel electrochemical strategy for nucleic
acid sequence identification assay has been developed. Through detecting the
redox signal mediated by AuNPs on 1, 6-hexanedithiol blocked gold electrode, the
proposed method is able to ensure substantial signal amplification and a low
background current. This strategy is demonstrated for quantitative analysis of
the target microRNA (let-7a) in human breast adenocarcinoma cells, and a
detection limit of 16 fM is readily achieved with desirable specificity and
sensitivity. These results indicate that the selective preconcentration of AuNPs
for electrochemical signal readout can offer a promising platform for the
detection of specific nucleic acid sequence.
PMID- 27506345
TI - Electrochemical DNA sensor-based strategy for sensitive detection of DNA
demethylation and DNA demethylase activity.
AB - DNA demethylation and demethylase activity play important roles in DNA self
repair, and their detection is key to early diagnosis of fatal diseases. Herein,
a facile electrochemical DNA (E-DNA) sensor was developed for the sensitive
detection of DNA demethylation and demethylase activity based on an enzyme
cleavage strategy. The thiol modified hemi-methylated hairpin probe DNA (pDNA)
was self-assembled on a Au electrode surface through the formation of AuS bonds.
The hemi-methylated pDNA served as the substrate of DNA demethylase (using methyl
CpG-binding domain protein 2 (MBD2) as an example). Following demethylation, the
hairpin stem was then recognized and cleaved by BstUI endonuclease. The ferrocene
carboxylic acid (FcA)-tagged pDNA strands were released into the buffer solution
from the electrode surface, resulting in a significant decrease of
electrochemical signal and providing a means to observe DNA demethylation. The
activity of DNA demethylase was analyzed in the concentration ranging from 0.5 to
500 ng mL(-1) with a limit of detection as low as 0.17 ng mL(-1). With high
specificity and sensitivity, rapid response, and low cost, this simple E-DNA
sensor provides a unique platform for the sensitive detection of DNA
demethylation, DNA demethylase activity, and related molecular diagnostics and
drug screening.
PMID- 27506346
TI - Aberrant sialylation of a prostate-specific antigen: Electrochemical label-free
glycoprofiling in prostate cancer serum samples.
AB - Electrochemical detection method allowing to detect prostate-specific antigen
(PSA), a biomarker of prostate cancer (PCa), with PSA glycoprofiling was applied
in an analysis of PCa serum samples for the first time. Electrochemical impedance
spectroscopy (EIS) as a label-free method with immobilized anti-PSA was applied
for PSA detection and lectins to glycoprofile captured PSA on the same surface. A
proper choice of blocking agent providing high selectivity of biosensor detection
with the immobilized anti-PSA antibody was done. The biosensor could detect PSA
down to 100 ag/mL with a linear concentration working range from 100 ag/mL up to
1 MUg/mL, i.e. 10 orders of concentration magnitude and the sensitivity of (5.5
+/- 0.2)%/decade. The results showed that a commercial carbo-free blocking
solution was the best one, reducing non-specific binding 55-fold when compared to
the immunosensor surface without any blocking agent applied, while allowing to
detect PSA. The biosensor response obtained after addition of lectin (i.e.
proportional to the amount of a particular glycan on PSA) divided by the
biosensor response obtained after incubation with a sample (i.e. proportional to
the PSA level in the sample) was applied to distinguish serum samples of PCa
patients from those of healthy individuals. The results showed that Maackia
amurensis agglutinin (MAA) recognizing alpha-2,3-terminal sialic acid can be
applied to distinguish between these two sets of samples since the MAA/PSA
response obtained from the analysis of the PCa samples was significantly higher
(5.3-fold) compared to the MAA/PSA response obtained by the analysis of samples
from healthy individuals. Thus, combined analysis of serological PSA levels
together with PSA glycoprofiling of aberrant glycosylation of PSA (i.e. increase
in the level of alpha-2,3-terminal sialic acid) has a potential to improve
detection of PCa.
PMID- 27506347
TI - Electromembrane extraction of polar basic drugs from plasma with pure bis(2
ethylhexyl) phosphite as supported liquid membrane.
AB - Electromembrane extraction (EME) of polar basic drugs from human plasma was
investigated for the first time using pure bis(2-ethylhexyl) phosphite (DEHPi) as
the supported liquid membrane (SLM). The polar basic drugs metaraminol,
benzamidine, sotalol, phenylpropanolamine, ephedrine, and trimethoprim were
selected as model analytes, and were extracted from 300 MUL of human plasma,
through 10 MUL of DEHPi as SLM, and into 100 MUL of 10 mM formic acid as acceptor
solution. The extraction potential across the SLM was 100 V, and extractions were
performed for 20 min. After EME, the acceptor solutions were analyzed by high
performance liquid chromatography-ultraviolet detection (HPLC-UV). In contrast to
other SLMs reported for polar basic drugs in the literature, the SLM of DEHPi was
highly stable in contact with plasma, and the system-current across the SLM was
easily kept below 50 MUA. Thus, electrolysis in the sample and acceptor solution
was kept at an acceptable level with no detrimental consequences. For the polar
model analytes, representing a log P range from -0.40 to 1.32, recoveries in the
range 25-91% were obtained from human plasma. Strong hydrogen bonding and dipole
interactions were probably responsible for efficient transfer of the model
analytes into the SLM, and this is the first report on efficient EME of highly
polar analytes without using any ionic carrier in the SLM.
PMID- 27506348
TI - Magnetic field assisted MU-solid phase extraction of anti-inflammatory and loop
diuretic drugs by modified polybutylene terephthalate nanofibers.
AB - A magnetic nanocomposite consisting of nanoparticles-polybutylene terephthalate
(MNPs-PBT) was electrospun and used as an extracting medium for an on-line MU
solid phase extraction (MU-SPE)-high performance liquid chromatography (HPLC) set
up with an ultraviolet (UV) detection system. Due to the magnetic property of the
prepared nanofibers, the whole extraction procedure was implemented under an
external magnetic field to enhance the extraction efficiencies. The developed
method along with the synthesized nanocomposite were found to be appropriate for
the determination of trace levels of selected drugs including furosemide,
naproxen, diclofenac and clobetasol propionate in the urine sample. The prepared
MNPs-PBT electrospun nanocomposite was characterized using the scanning electron
microscopy (SEM), energy dispersive spectroscopy (EDX) and Fourier transform
infrared (FT-IR) spectroscopy. The prepared magnetic fibers showed high porosity,
which was another driving force for the extraction efficiency enhancement. Major
parameters affecting the extraction efficiency of the selected drugs were
optimized. The limits of detections (LOD) of the studied drugs were in the range
of 0.4-1.6 MUg L(-1) and the limits of quantification (LOQ) were 1-4 MUg L(-1)
under the optimized conditions. Relative standard deviation (RSD%) for three
replicates at three concentration levels of 6, 100 and 400 MUg L(-1) were 5.9
8.0% while acceptable linear range with two orders of magnitude was obtained
(R(2) = 0.99). The method was validated by the determination of the selected
drugs in urine samples and the results indicated that this method has sufficient
potential for enrichment and determination of the desired drugs in the urine
sample. The relative recovery values were found to be in the range of 78-91%.
Implementing the developed on-line MU-SPE method under the external magnetic
field induction, led to higher extraction efficiencies for the selected drugs
with various diamagnetic properties.
PMID- 27506349
TI - Impedometric monitoring of the behavior of the supported liquid membrane in
electromembrane extraction systems: An insight into the origin of optimized
experimental parameters.
AB - Electromembrane extraction (EME) was carried out using a novel instrumentation
capable of impedometric monitoring of the system during the extraction. This
instrumentation involves a classical two-electrode assembly fed by two time
resolved potential functions, the first for the extraction of analyte and the
second for obtaining the impedance information. The impedometric analysis of the
system was achieved by Laplace transformation of the current recorded during the
extraction. It has been shown that the obtained impedance information can be
converted to very useful knowledge about time dependence of double layer
capacitance, kinetics of analyte depletion, total permeability of the SLM and the
effect of experimental parameters on system behavior. It has also been shown that
the impedance analysis is a powerful tool for the estimation of optimum
experimental parameters without determination of analyte in the acceptor phase.
PMID- 27506350
TI - Magnetic ionic liquids as non-conventional extraction solvents for the
determination of polycyclic aromatic hydrocarbons.
AB - This work describes the applicability of magnetic ionic liquids (MILs) in the
analytical determination of a group of heavy polycyclic aromatic hydrocarbons.
Three different MILs, namely, benzyltrioctylammonium bromotrichloroferrate (III)
(MIL A), methoxybenzyltrioctylammonium bromotrichloroferrate (III) (MIL B), and
1,12-di(3-benzylbenzimidazolium) dodecane bis[(trifluoromethyl)sulfonyl)]imide
bromotrichloroferrate (III) (MIL C), were designed to exhibit hydrophobic
properties, and their performance examined in a microextraction method for
hydrophobic analytes. The magnet-assisted approach with these MILs was performed
in combination with high performance liquid chromatography and fluorescence
detection. The study of the extraction performance showed that MIL A was the most
suitable solvent for the extraction of polycyclic aromatic hydrocarbons and under
optimum conditions the fast extraction step required ~20 MUL of MIL A for 10 mL
of aqueous sample, 24 mmol L(-1) NaOH, high ionic strength content of NaCl (25%
(w/v)), 500 MUL of acetone as dispersive solvent, and 5 min of vortex. The
desorption step required the aid of an external magnetic field with a strong
NdFeB magnet (the separation requires few seconds), two back-extraction steps for
polycyclic aromatic hydrocarbons retained in the MIL droplet with n-hexane,
evaporation and reconstitution with acetonitrile. The overall method presented
limits of detection down to 5 ng L(-1), relative recoveries ranging from 91.5 to
119%, and inter-day reproducibility values (expressed as relative standard
derivation) lower than 16.4% for a spiked level of 0.4 MUg L(-1) (n = 9). The
method was also applied for the analysis of real samples, including tap water,
wastewater, and tea infusion.
PMID- 27506351
TI - Facile synthesis of multifunctional attapulgite/Fe3O4/polyaniline nanocomposites
for magnetic dispersive solid phase extraction of benzoylurea insecticides in
environmental water samples.
AB - In this study, the superparamagnetic attapulgite/Fe3O4/polyaniline
(ATP/Fe3O4/PANI) nanocomposites were successfully synthesized by a one-pot
method. Fe (III) was applied as both the oxidant for the oxidative polymerization
of aniline and the single iron source of Fe3O4 formed by the redox reaction
between aniline and Fe (III). The ATP/Fe3O4/PANI was used as sorbent for magnetic
dispersive solid phase extraction (MDSPE) of benzoylurea insecticides (BUs) in
environmental water samples. The as-prepared nanocomposite sorbents were
characterized by Fourier transform infrared spectra (FT-IR), X Ray diffraction
(XRD), scanning electron microscopy(SEM), transmission electron microscopy (TEM),
and vibrating sample magnetometry. Various experimental parameters affecting the
ATP/Fe3O4/PANI-based MDSPE procedure, including the composition of the
nanocomposite sorbents, amount of ATP/Fe3O4/PANI nanocomposites, vortex time, pH,
and desorption conditions were investigated. Under the optimal conditions, a good
linearity was observed for all target analytes, with correlation coefficients
(r(2)) ranging from 0.9985 to 0.9997; the limits of detection (LOD) were in the
range of 0.02-0.43 MUg L(-1), and the recoveries of analytes using the proposed
method ranged between 77.37% and 103.69%. The sorbents exhibited an excellent
reproducibility in the range of 1.52-5.27% in extracting the five target
analytes. In addition, the intra-day and inter-day precision values were found to
be in the range of 0.78-6.86% and 1.66-8.41%, respectively. Finally, the proposed
ATP/Fe3O4/PANI-based MDSPE method was successfully applied to analyze river water
samples by rapid preconcentration of BUs.
PMID- 27506352
TI - In situ hydrothermal growth of ZnO/g-C3N4 nanoflowers coated solid-phase
microextraction fibers coupled with GC-MS for determination of pesticides
residues.
AB - In this paper, Zinc oxide (ZnO) hybridized with graphite-like C3N4 (ZnO/g-C3N4)
nanoflowers based solid phase microextraction (SPME) coating was prepared on
fiber using in situ hydrothermal growth method for gas chromatographic -mass
spectrum (GC- MS) separation and analysis target analytes in complex matrixes for
the first time. The proposed hybrid ZnO/g-C3N4 fiber exhibited wide linearity for
the pesticide residues in range of 0.003-5.0 ng mL(-1). The limits of detection
(LOD) were 0.001-0.0025 ng mL(-1). The relative standard deviation (RSD) for
three replicate extractions using one fiber was ranged from 2.3% to 7.6%. The
fiber to fiber RSD was 5.3-11.3% (n = 3). This method was successfully used for
simultaneous determination of nine pesticide residues in cucumber, pear, Green
tea and Minjiang water with satisfactory recoveries of 79.1-103.5%. These results
indicated that the ZnO/g-C3N4 composite provided a promising alternative in
sample pretreatment and analysis.
PMID- 27506353
TI - A novel approach to Lab-In-Syringe Head-Space Single-Drop Microextraction and on
drop sensing of ammonia.
AB - A novel approach to the automation technique Lab-In-Syringe, also known as In
Syringe Analysis, is proposed which utilizes a secondary inlet into the syringe
void, used as a size-adaptable reaction chamber, via a channel passing through
the syringe piston. This innovative approach allows straightforward automation of
head-space single-drop microextraction, involving accurately controlled drop
formation and handling, and the possibility of on-drop analyte quantification.
The syringe was used in upside-down orientation and in-syringe magnetic stirring
was carried out, which allowed homogenous mixing of solutions, promotion of head
space analyte enrichment, and efficient syringe cleaning. The superior
performance of the newly developed system was illustrated with the development of
a sensitive method for total ammonia determination in surface waters. It is based
on head-space extraction of ammonia into a single drop of bromothymol blue
indicator created inside the syringe at the orifice of the syringe piston channel
and on-drop sensing of the color change via fiber optics. The slope of the linear
relationship between absorbance and time was used as the analytical signal. Drop
formation and performance of on-drop monitoring was further studied with
rhodamine B solution to give a better understanding of the system's performance.
A repeatability of 6% RSD at 10 MUmol L(-1) NH3, a linear range of up to 25 MUmol
L(-1) NH3, and a limit of detection of 1.8 MUmol L(-1) NH3 were achieved. Study
of interferences proved the high robustness of the method towards humic acids,
high sample salinity, and the presence of detergents, thus demonstrating the
method superiority compared to the state-of-the-art gas-diffusion methods. A mean
analyte recovery of 101.8% was found in analyzing spiked environmental water
samples.
PMID- 27506354
TI - Highly specific purification of N-glycans using phosphate-based derivatization as
an affinity tag in combination with Ti(4+)-SPE enrichment for mass spectrometric
analysis.
AB - N-linked protein glycosylation is involved in regulation of a wide variety of
cellular processes and associated with numerous diseases. Highly specific
identification of N-glycome remains a challenge while its biological significance
is acknowledged. The relatively low abundance of glycan in complex biological
mixtures, lack of basic sites for protonation, and suppression by other highly
abundant proteins/peptides lead to the particularly poor detection sensitivity of
N-glycans in the MS analysis. Therefore, the highly specific purification
procedure becomes a crucial step prior to MS analysis of the N-glycome. Herein, a
novel N-glycans enrichment approach based on phosphate derivatization combined
with Ti(4+)-SPE (solid phase extraction) was developed. Briefly, in this
strategy, N-glycans were chemically labeled with a phospho-group at their
reducing ends, such that the Ti(4+)-SPE microspheres were able to capture the
phospho-containing glycans. The enrichment method was developed and optimized
using model oligosaccharides (maltoheptaose DP7 and sialylated glycan A1) and
also glycans from a standard glycoprotein (asialofetuin, ASF). This method
experimentally showed high derivatization efficiency (almost 100%), excellent
selectivity (analyzing DP7 in the digests of bovine serum albumin at a mass ratio
of 1:100), high enriching recovery (90%), good reproducibility (CV<15%) as well
as high sensitivity (LOD at fmol level). At last, the proposed method was
successfully applied in the profiling of N-glycome in human serum, in which a
total of 31 N-glycan masses were identified.
PMID- 27506355
TI - Direct glycan structure determination of intact N-linked glycopeptides by low
energy collision-induced dissociation tandem mass spectrometry and predicted
spectral library searching.
AB - Intact glycopeptide MS analysis to reveal site-specific protein glycosylation is
an important frontier of proteomics. However, computational tools for analyzing
MS/MS spectra of intact glycopeptides are still limited and not well-integrated
into existing workflows. In this work, a new computational tool which combines
the spectral library building/searching tool, SpectraST (Lam et al. Nat.
Methods2008, 5, 873-875), and the glycopeptide fragmentation prediction tool,
MassAnalyzer (Zhang et al. Anal. Chem.2010, 82, 10194-10202) for intact
glycopeptide analysis has been developed. Specifically, this tool enables the
determination of the glycan structure directly from low-energy collision-induced
dissociation (CID) spectra of intact glycopeptides. Given a list of possible
glycopeptide sequences as input, a sample-specific spectral library of
MassAnalyzer-predicted spectra is built using SpectraST. Glycan identification
from CID spectra is achieved by spectral library searching against this library,
in which both m/z and intensity information of the possible fragmentation ions
are taken into consideration for improved accuracy. We validated our method using
a standard glycoprotein, human transferrin, and evaluated its potential to be
used in site-specific glycosylation profiling of glycoprotein datasets from LC
MS/MS. In addition, we further applied our method to reveal, for the first time,
the site-specific N-glycosylation profile of recombinant human
acetylcholinesterase expressed in HEK293 cells. For maximum usability, SpectraST
is developed as part of the Trans-Proteomic Pipeline (TPP), a freely available
and open-source software suite for MS data analysis.
PMID- 27506356
TI - Rapid and reliable species identification of wild mushrooms by matrix assisted
laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS).
AB - Mushrooms are a favourite natural food in many countries. However, some wild
species cause food poisoning, sometimes lethal, due to misidentification caused
by confusing fruiting bodies similar to those of edible species. The
morphological inspection of mycelia, spores and fruiting bodies have been
traditionally used for the identification of mushrooms. More recently, DNA
sequencing analysis has been successfully applied to mushrooms and to many other
species. This study focuses on a simpler and more rapid methodology for the
identification of wild mushrooms via protein profiling based on matrix-assisted
laser desorption/ionization mass spectrometry (MALDI-TOF MS). A preliminary study
using 6 commercially available cultivated mushrooms suggested that a more
reproducible spectrum was obtained from a portion of the cap than from the stem
of a fruiting body by the extraction of proteins with a formic acid-acetonitrile
mixture (1 + 1). We used 157 wild mushroom-fruiting bodies collected in the
centre of Hokkaido from June to November 2014. Sequencing analysis of a portion
of the ribosomal RNA gene provided 134 identifications of mushrooms by genus or
species, however 23 samples containing 10 unknown species that had lower
concordance rate of the nucleotide sequences in a BLAST search (less than 97%)
and 13 samples that had unidentifiable poor or mixed sequencing signals remained
unknown. MALDI-TOF MS analysis yielded a reproducible spectrum (frequency of
matching score >= 2.0 was >=6 spectra from 12 spectra measurements) for 114 of
157 samples. Profiling scores that matched each other within the database gave
correct species identification (with scores of >=2.0) for 110 samples (96%). An
in-house prepared database was constructed from 106 independent species, except
for overlapping identifications. We used 48 wild mushrooms that were collected in
autumn 2015 to validate the in-house database. As a result, 21 mushrooms were
identified at the species level with scores >=2.0 and 5 mushrooms at the genus
level with scores >=1.7, although the signals of 2 mushrooms were insufficient
for analysis. The remaining 20 samples were recognized as "unreliable
identification" with scores <1.7. Subsequent DNA analysis confirmed that the
correct species or genus identifications were achieved by MALDI-TOF MS for the 26
former samples, whereas the 18 mushrooms with poorly matched scores were species
that were not included in the database. Thus, the proposed MALDI-TOF MS coupled
with our database could be a powerful tool for the rapid and reliable
identification of mushrooms; however, continuous updating of the database is
necessary to enrich it with more abundant species.
PMID- 27506357
TI - Bioanalysis of dried saliva spot (DSS) samples using detergent-assisted sample
extraction with UHPLC-MS/MS detection.
AB - Dried saliva spot (DSS) sampling is a non-invasive sample collection technique
for bioanalysis that can be potentially implemented at the patient's home. A
UHPLC-MS/MS assay was developed using detergent-assisted sample extraction to
quantify BMS-927711, a drug candidate in development for the treatment of
migraines, in human DSS. By implementing DSS sampling at the patients' home, the
bioanalytical sample collection for pharmacokinetic evaluation can be done at the
time of the acute migraine attack without the need for clinical visits. DSS
samples were prepared by spotting 15 MUL of liquid saliva onto regular Whatman
FTATM DMPK-C cards and verified with a UV lamp (at lambda 254 nm or 365 nm)
during DSS punching. The 4-mm DSS punches in a 96-well plate were sonicated with
200 MUL of [(13)C2, D4]-BMS-927711 internal standard (IS) solution in 20/80
MeOH/water for 10 min, followed by sonication with 50 MUL of 100 mM NH4OAc with
1.0% Triton-X-100 (as detergent) prior to liquid-liquid extraction with 600 MUL
EtOAc/Hexane (90:10). UHPLC-MS/MS was performed with an Aquity((r)) UPLC BEH C18
Column (2.1 * 50 mm, 1.7 MUm) on a Triple QuadTM 5500 mass spectrometer. The
assay was linear with a concentration range from 2.00 to 1000 ng mL(-1) for BMS
927711 in human saliva. The intra- and inter-assay precision was within 8.8% CV,
and the accuracy was within +/-6.7% Dev of the nominal concentration values. This
UHPLC-MS/MS assay has been successfully applied to determine the drug's
pharmacokinetics within a clinical study. For the first time, we observed BMS
927711 exposure in human DSS, confirming the suitability of this sampling
technique for migraine patients to use at home. Detergent-assisted extraction
with Triton-X-100 could be very useful in DSS or other dried matrix spot (DMS)
assays to overcome low or inconsistent analyte recovery issues.
PMID- 27506358
TI - A new sample preparation and separation combination for precise, accurate, rapid,
and simultaneous determination of vitamins B1, B2, B3, B5, B6, B7, and B9 in
infant formula and related nutritionals by LC-MS/MS.
AB - An improved method was developed for simultaneous determination of the fortified
forms of thiamine (B1), riboflavin (B2), nicotinamide and nicotinic acid (B3),
pantothenic acid (B5), pyridoxine (B6), biotin (B7), and folic acid (B9) in
infant formulas and related nutritionals. The method employed a simple,
effective, and rapid sample preparation followed by liquid chromatography tandem
mass spectrometry (LC-MS/MS). It improved upon previous methodologies by offering
facile and rugged sample preparation with improved chromatographic conditions,
which culminated in a highly accurate and precise method for water-soluble
vitamin determination in a wide range of formulas. The method was validated over
six days in ten unique matrices with two analysts and on instruments in two
different labs. Intermediate precision averaged 3.4 +/- 2.6% relative standard
deviation and over-spike recovery averaged 100.2 +/- 2.4% (n = 160). Due to
refinements in sample preparation, the method had high sample throughput
capacity.
PMID- 27506359
TI - Development of a blood-brain barrier model in a membrane-based microchip for
characterization of drug permeability and cytotoxicity for drug screening.
AB - Since most of the central nervous system (CNS) drug candidates show poor
permeability across the blood-brain barrier (BBB), development of a reliable
platform for permeability assay will greatly accelerate drug discovery. Herein,
we constructed a microfluidic BBB model to mimic drug delivery into the brain to
induce cytotoxicity at target cells. To reconstitute the in vivo BBB properties,
human cerebral microvessel endothelial cells (hCMEC/D3) were dynamically cultured
in a membrane-based microchannel. Sunitinib, a model drug, was then delivered
into the microchannel and forced to permeate through the BBB model. The permeated
amount was directly quantified by an electrospray ionization quadrupole time-of
flight mass spectrometer (ESI-Q-TOF MS) after on-chip SPE (MUSPE) pretreatment.
Moreover, the permeated drug was incubated with glioma cells (U251) cultured
inside agarose gel in the downstream to investigate drug-induced cytotoxicity.
The resultant permeability of sunitinib was highly correlated with literature
reported value, and it only required 30 min and 5 MUL of sample solution for each
permeation experiment. Moreover, after 48 h of treatment, the survival rate of
U251 cells cultured in 3D scaffolds was nearly 6% higher than that in 2D, which
was in accordance with the previously reported results. These results demonstrate
that this platform provides a valid tool for drug permeability and cytotoxicity
assays which have great value for the research and development of CNS drugs.
PMID- 27506360
TI - Software-assisted serum metabolite quantification using NMR.
AB - The goal of metabolomics is to analyze a whole metabolome under a given set of
conditions, and accurate and reliable quantitation of metabolites is crucial.
Absolute concentration is more valuable than relative concentration; however, the
most commonly used method in NMR-based serum metabolic profiling, bin-based and
full data point peak quantification, provides relative concentration levels of
metabolites and are not reliable when metabolite peaks overlap in a spectrum. In
this study, we present the software-assisted serum metabolite quantification
(SASMeQ) method, which allows us to identify and quantify metabolites in NMR
spectra using Chenomx software. This software uses the ERETIC2 utility from
TopSpin to add a digitally synthesized peak to a spectrum. The SASMeQ method will
advance NMR-based serum metabolic profiling by providing an accurate and reliable
method for absolute quantification that is superior to bin-based quantification.
PMID- 27506361
TI - Exploiting multi-function Metal-Organic Framework nanocomposite Ag@Zn-TSA as
highly efficient immobilization matrixes for sensitive electrochemical
biosensing.
AB - A novel multi-function Metal-Organic Framework composite Ag@Zn-TSA (zinc
thiosalicylate, Zn(C7H4O2S), Zn-TSA) was synthesized as highly efficient
immobilization matrixes of myoglobin (Mb)/glucose oxidase (GOx) for
electrochemical biosensing. The electrochemical biosensors based on Ag@Zn-TSA
composite and ionic liquid (IL) modified carbon paste electrode (CPE) were
fabricated successfully. Furthermore, the properties of the sensors were
discussed by cyclic voltammetry (CV), electrochemical impedance spectroscopy
(EIS) and amperometric current-time curve, respectively. The results showed the
proposed biosensors had wide linear response to hydrogen peroxide (H2O2) in the
range of 0.3-20,000 MUM, to nitrite (NO2(-)) for 1.3 MUM-1660 MUM and 2262 MUM
1,33,000 MUM, to glucose for 2.0-1022 MUM, with a low detection limit of 0.08 MUM
for H2O2, 0.5 MUM for NO2(-), 0.8 MUM for glucose. The values of the apparent
heterogeneous electron transfer rate constant (ks) for Mb and GOx were estimated
as 2.05 s(-1) and 2.45 s(-1), respectively. Thus, Ag@Zn-TSA was a kind of ideal
material as highly efficient immobilization matrixes for sensitive
electrochemical biosensing. In addition, this work indicated that MOF
nanocomposite had a great potential for constructing wide range of sensing
interface.
PMID- 27506362
TI - Three dimensional graphene transistor for ultra-sensitive pH sensing directly in
biological media.
AB - In this work, pH sensing directly in biological media using three dimensional
liquid gated graphene transistors is presented. The sensor is made of suspended
network of graphene coated all around with thin layer of hafnium oxide (HfO2),
showing high sensitivity and sensing beyond the Debye-screening limit. The
performance of the pH sensor is validated by measuring the pH of isotonic
buffered, Dulbecco's phosphate buffered saline (DPBS) solution, and of blood
serum derived from Sprague-Dawley rat. The pH sensor shows high sensitivity of 71
+/- 7 mV/pH even in high ionic strength media with molarities as high as 289 +/-
1 mM. High sensitivity of this device is owing to suspension of three dimensional
graphene in electrolyte which provides all around liquid gating of graphene,
leading to higher electrostatic coupling efficiency of electrolyte to the channel
and higher gating control of transistor channel by ions in the electrolyte.
Coating graphene with hafnium oxide film (HfO2) provides binding sites for
hydrogen ions, which results in higher sensitivity and sensing beyond the Debye
screening limit. The 3D graphene transistor offers the possibility of real-time
pH measurement in biological media without the need for desaltation or sample
preparation.
PMID- 27506363
TI - Rhodamine-based chemodosimeter for fluorescent determination of Hg(2+) in 100%
aqueous solution and in living cells.
AB - A rhodamine spirolactam derivative (1) bearing a hydrophilic carboxylic acid
group is developed as a fluorescent chemodosimeter for bivalent mercury ions
(Hg(2+)) in 100% aqueous solution. It exhibits a highly sensitive "turn-on"
fluorescent response toward Hg(2+) with a 42-fold fluorescence intensity
enhancement under 1 equiv. of Hg(2+) added. The chemodosimeter can be applied to
the quantification of Hg(2+) with a linear range covering from 3.0 * 10(-7) to
1.0 * 10(-5) M and a detection limit of 9.7 * 10(-8) M. Most importantly, the
fluorescence changes of the chemodosimeter are remarkably specific for Hg(2+) in
the presence of other metal ions, which meet the selective requirements for
practical application. Moreover, the experiment results show that the response
behavior of 1 towards Hg(2+) is pH independent in neutral condition (pH 5.0-8.0)
and the response is fast (response time less than 3 min). Furthermore, the ring
opening mechanism of the rhodamine spirolactam induced by Hg(2+) was supported by
NMR, MS, and DFT theoretical calculations. In addition, the proposed
chemodosimeter has been used to detect Hg(2+) in water samples and image Hg(2+)
in living cells with satisfying results.
PMID- 27506364
TI - A redox-mediated chromogenic reaction and application in immunoassay.
AB - A novel redox-mediated chromogenic reaction was demonstrated based on the
reaction between HAuCl4 and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
(ABTS), which generate various color responses from red to green in the resulting
solutions. Various redox substance could be used to mediate the reaction and
trigger a distinct color response. We established a sensitive hydrogen peroxide
colorimetric sensor based on the redox-mediated chromogenic reaction and depicted
the application both in detection of enzyme and in an immunoassay. Combining the
traditional chromogenic reagent with gold nanoparticles, our assay has the
advantage in short response time (within three minutes), high sensitivity (10(
12) g mL(-1) for HBsAg) and stability.
PMID- 27506365
TI - One step derivatization with British Anti-Lewsite in combination with gas
chromatography coupled to triple-quadrupole tandem mass spectrometry for the fast
and selective analysis of inorganic arsenic in rice.
AB - We developed a new fast and selective analytical method for the determination of
inorganic arsenic (iAs) in rice by a gas chromatography - tandem mass
spectrometry (GC-MS/MS) in combination with one step derivatization of inorganic
arsenic (iAs) with British Anti-Lewsite (BAL). Two step derivatization of iAs
with BAL has been previously performed for the GC-MS analysis. In this paper, the
quantitative one step derivatization condition was successfully established. The
GC-MS/MS was carried out with a short nonpolar capillary column (0.25 mm * 10 m)
under the conditions of fast oven temperature ramp rate (4 degrees C/s) and high
linear velocity (108.8 cm/s) of the carrier gas. The established GC-MS/MS method
showed an excellent linearity (r(2) > 0.999) in a tested range (0.2-100.0 MUg L(
1)), ultra-low limit of detection (LOD, 0.08 pg), and high precision and
accuracy. The GC-MS/MS technique showed far greater selectivity (22.5 fold higher
signal to noise ratio in rice sample) on iAs than GC-MS method. The gas
chromatographic running time was only 2.5 min with the iAs retention time of 1.98
min. The established method was successfully applied to quantify the iAs contents
in polished rice. The mean iAs content in the Korean polished rice (n = 27) was
66.1 MUg kg(-1) with the range of 37.5-125.0 MUg kg(-1). This represents the
first report on the GC-tandem mass spectrometry in combination with the one step
derivatization with BAL for the iAs speciation in rice. This GC-MS/MS method
would be a simple, useful and reliable measure for the iAs analysis in rice in
the laboratories in which the expensive and element specific HPLC-ICP-MS is not
available.
PMID- 27506366
TI - Enantioselective simultaneous analysis of selected pharmaceuticals in
environmental samples by ultrahigh performance supercritical fluid based
chromatography tandem mass spectrometry.
AB - In order to assess the true impact of each single enantiomer of pharmacologically
active compounds (PACs) in the environment, highly efficient, fast and sensitive
analytical methods are needed. For the first time this paper focuses on the use
of ultrahigh performance supercritical fluid based chromatography coupled to a
triple quadrupole mass spectrometer to develop multi-residue enantioselective
methods for chiral PACs in environmental matrices. This technique exploits the
advantages of supercritical fluid chromatography, ultrahigh performance liquid
chromatography and mass spectrometry. Two coated modified 2.5 MUm-polysaccharide
based chiral stationary phases were investigated: an amylose tris-3,5
dimethylphenylcarbamate column and a cellulose tris-3-chloro-4
methylphenylcarbamate column. The effect of different chromatographic variables
on chiral recognition is highlighted. This novel approach resulted in the
baseline resolution of 13 enantiomers PACs (aminorex, carprofen, chloramphenicol,
3-N-dechloroethylifosfamide, flurbiprofen, 2-hydroxyibuprofen, ifosfamide,
imazalil, naproxen, ofloxacin, omeprazole, praziquantel and tetramisole) and
partial resolution of 2 enantiomers PACs (ibuprofen and indoprofen) under fast
gradient conditions (<10 min analysis time). The overall performance of the
methods was satisfactory. The applicability of the methods was tested on influent
and effluent wastewater samples. To the best of our knowledge, this is the first
feasibility study on the simultaneous separation of chemically diverse chiral
PACs in environmental matrices using ultrahigh performance supercritical fluid
based chromatography coupled with tandem mass spectrometry.
PMID- 27506367
TI - Development and optimization of ultra-high performance supercritical fluid
chromatography mass spectrometry method for high-throughput determination of
tocopherols and tocotrienols in human serum.
AB - The goal of this study was to develop an effective supercritical fluid
chromatography method using single quadrupole MS for analysis of all isomeric
forms of vitamin E. Finally, two fast and effective methods, the high resolution
one and the high speed one, for the determination of 8 vitamin E isomers in human
serum were developed. Rapid high-throughput liquid-liquid extraction was selected
as a sample preparation step. Sample pretreatment of 100 MUL human serum was
consisted of protein precipitation with 200 MUL ethanol and liquid-liquid
extraction by 400 MUL hexane/dichloromethane (80/20, v/v). The separation was
performed on BEH 2-EP (3.0 * 100 mm, 1.7 MUm) stationary phase, using isocratic
elution with carbon dioxide and 10 mM ammonium formate in methanol in the ratio
98:2 for high resolution method with run time 4.5 min and in the ratio 95:5 for
high speed method, where the run time was 2.5 min. The method development
included optimization of key parameters: the choice of the suitable stationary
phase and the composition of mobile phase, where an influence of various
modifiers, their ratio and additives were tested, and optimization of fine
tunning parameters including BPR pressure, flow-rate and column temperature.
Quantification of all isomeric forms was performed using SIM (single ion
monitoring) experiments in ESI positive ion mode. Both high speed and high
resolution chromatographic methods were validated in terms of precision,
accuracy, range, linearity, LOD, LOQ and matrix effects using the same LLE
procedure. The high resolution method provided more sensitive results (LOD: 0.017
0.083 MUg mL(-1)) and better linearity (r(2) > 0.9930) than the high speed one
(LOD: 0.083-0.25 MUg mL(-1), r(2) > 0.9877) at the cost of double time of
analysis.
PMID- 27506368
TI - Ictal asystole mimicking seizure deterioration in temporal lobe epilepsy.
PMID- 27506369
TI - Functional lignocellulosic materials prepared by ATRP from a wood scaffold.
AB - Wood, a natural and abundant source of organic polymers, has been used as a
scaffold to develop novel wood-polymer hybrid materials. Through a two-step
surface-initiated Atom Transfer Radical Polymerization (ATRP), the porous wood
structure can be effectively modified with polymer chains of various nature. In
the present study, polystyrene and poly(N-isopropylacrylamide) were used. As
shown with various characterization techniques including confocal Raman
microscopy, FTIR, and SEM/EDX, the native wood ultrastructure and features are
retained and the polymer chains can be introduced deep within the wood, i.e.
inside the wood cell walls. The physical properties of the new materials have
been studied, and results indicate that the insertion of polymer chains inside
the wood cell wall alters the intrinsic properties of wood to yield a hybrid
composite material with new functionalities. This approach to the
functionalization of wood could lead to the fabrication of a new class of
interesting functional materials and promote innovative utilizations of the
renewable resource wood.
PMID- 27506370
TI - Template-mediated Synthesis of Hollow Microporous Organic Nanorods with Tunable
Aspect Ratio.
AB - Hollow microporous organic nanorods (HMORs) with hypercrosslinked polymer (HCPs)
shells were synthesized through emulsion polymerization followed by
hypercrosslinking. The HMORs have tunable aspect ratios, high BET surface areas
and monodispersed morphologies, showing good performance in gas adsorpion.
PMID- 27506371
TI - Purely electronic mechanism of electrolyte gating of indium tin oxide thin films.
AB - Epitaxial indium tin oxide films have been grown on both LaAlO3 and yttria
stabilized zirconia substrates using RF magnetron sputtering. Electrolyte gating
causes a large change in the film resistance that occurs immediately after the
gate voltage is applied, and shows no hysteresis during the charging/discharging
processes. When two devices are patterned next to one another and the first one
gated through an electrolyte, the second one shows no changes in conductance, in
contrast to what happens in materials (like tungsten oxide) susceptible to ionic
electromigration and intercalation. These findings indicate that electrolyte
gating in indium tin oxide triggers a pure electronic process (electron depletion
or accumulation, depending on the polarity of the gate voltage), with no
electrochemical reactions involved. Electron accumulation occurs in a very thin
layer near the film surface, which becomes highly conductive. These results
contribute to our understanding of the electrolyte gating mechanism in complex
oxides and may be relevant for applications of electric double layer transistor
devices.
PMID- 27506373
TI - Expediting Viral Therapies For Cancers To the Clinic.
PMID- 27506372
TI - Tsr Chemoreceptor Interacts With IL-8 Provoking E. coli Transmigration Across
Human Lung Epithelial Cells.
AB - Bacterial colonization of epithelial surfaces and subsequent transmigration
across the mucosal barrier are essential for the development of infection. We
hypothesized that the methyl-accepting proteins (MCPs), known as chemoreceptors
expressed on Escherichia coli (E. coli) bacterial surface, play an important role
in mediating bacterial transmigration. We demonstrated a direct interaction
between human interleukin-8 (IL-8) and Tsr receptor, a major MCP chemoreceptor.
Stimulation of human lung epithelial cell monolayer with IL-8 resulted in
increased E. coli adhesion and transmigration of the native strain (RP437) and a
strain expressing only Tsr (UU2373), as compared to a strain (UU2599) with Tsr
truncation. The augmented E. coli adhesion and migration was associated with a
higher expression of carcinoembryonic antigen-related cell adhesion molecule 6
and production of inflammatory cytokines/chemokines, and a lower expression of
the tight junction protein claudin-1 and the plasma membrane protein caveolin-1
in lung epithelial cells. An increased E. coli colonization and pulmonary
cytokine production induced by the RP437 and UU2373 strains was attenuated in
mice challenged with the UU2599 strain. Our results suggest a critical role of
the E. coli Tsr chemoreceptor in mediating bacterial colonization and
transmigration across human lung epithelium during development of pulmonary
infections.
PMID- 27506376
TI - The Role of Nonhuman Primate Animal Models in the Clinical Development of
Pluripotent Stem Cell Therapies.
PMID- 27506377
TI - Socializing Individualized T-Cell Cancer Immunotherapy.
PMID- 27506378
TI - Rethinking the Regulatory Infrastructure for Human Gene Transfer Clinical Trials.
PMID- 27506379
TI - Effects of long-term continuous cropping on soil nematode community and soil
condition associated with replant problem in strawberry habitat.
AB - Continuous cropping changes soil physiochemical parameters, enzymes and
microorganism communities, causing "replant problem" in strawberry cultivation.
We hypothesized that soil nematode community would reflect the changes in soil
conditions caused by long-term continuous cropping, in ways that are consistent
and predictable. To test this hypothesis, we studied the soil nematode
communities and several soil parameters, including the concentration of soil
phenolic acids, organic matter and nitrogen levels, in strawberry greenhouse
under continuous-cropping for five different durations. Soil pH significantly
decreased, and four phenolic acids, i.e., p-hydroxybenzoic acid, ferulic acid,
cinnamic acid and p-coumaric acid, accumulated with time under continuous
cropping. The four phenolic acids were highly toxic to Acrobeloides spp., the
eudominant genus in non-continuous cropping, causing it to reduce to a resident
genus after seven-years of continuous cropping. Decreased nematode diversity
indicated loss of ecosystem stability and sustainability because of continuous
cropping practice. Moreover, the dominant decomposition pathway was altered from
bacterial to fungal under continuous cropping. Our results suggest that along
with the continuous-cropping time in strawberry habitat, the soil food web is
disturbed, and the available plant nutrition as well as the general health of the
soil deteriorates; these changes can be indicated by soil nematode community.
PMID- 27506380
TI - Solvent-driven electron trapping and mass transport in reduced graphites to
access perfect graphene.
AB - Herein, we report on a significant discovery, namely, the quantitative
discharging of reduced graphite forms, such as graphite intercalation compounds,
graphenide dispersions and graphenides deposited on surfaces with the simple
solvent benzonitrile. Because of its comparatively low reduction potential,
benzonitrile is reduced during this process to the radical anion, which exhibits
a red colour and serves as a reporter molecule for the quantitative determination
of negative charges on the carbon sheets. Moreover, this discovery reveals a very
fundamental physical-chemical phenomenon, namely a quantitative solvent reduction
induced and electrostatically driven mass transport of K(+) ions from the
graphite intercalation compounds into the liquid. The simple treatment of
dispersed graphenides suspended on silica substrates with benzonitrile leads to
the clean conversion to graphene. This unprecedented procedure represents a
rather mild, scalable and inexpensive method for graphene production surpassing
previous wet-chemical approaches.
PMID- 27506381
TI - Correlation between the lateral pterygoid muscle attachment type and
temporomandibular joint disc position in magnetic resonance imaging.
AB - OBJECTIVES: The aim of this study was to investigate the correlation between the
lateral pterygoid muscle (LPM) attachment type and temporomandibular joint (TMJ)
disc position on sagittal and coronal MR scans. METHODS: 191 patients (148
females, 43 males), aged 14-60 years, underwent MR investigations of the TMJs in
the intercuspal position (IP) and open-mouth position (OMP). The disc position
was evaluated on oblique sagittal and coronal images in the IP and OMP on many
MRI sections showing all portions of the joint. Relationships between the LPM
attachment patterns and articular disc positions were evaluated by z and chi2
tests. RESULTS: Three types of the LPM attachment were found. There was a
statistically significant correlation between the LPM attachment type and the
disc position in IP (chi2 = 24.29; p < 0.01). The type of muscle attachment did
not determine the prevalence of normal, lateral and medial disc positions. There
were differences between the muscle attachment types in the anterior,
anteromedial and anterolateral disc positions. There was a statistically
significant association between TMJ disc position in OMP and particular
attachment types in the sagittal plane (chi2 = 9.702; p < 0.01). CONCLUSIONS:
Certain types of the LPM insertion are correlated with TMJ disc position.
PMID- 27506382
TI - Contribution of prostanoid signaling to the evolution of spreading depolarization
and the associated cerebral blood flow response.
AB - The significance of prostanoid signaling in neurovascular coupling during
somatosensory stimulation is increasingly more appreciated, yet its involvement
in mediating the cerebral blood flow (CBF) response to spreading depolarization
(SD) has remained inconclusive. Selective cyclooxygenase (COX) enzyme inhibitors
(NS-398, SC-560) or an antagonist (L161,982) of the EP4 type prostaglandin E2
receptor were applied topically to a cranial window over the parietal cortex of
isoflurane-anesthetized Sprague-Dawley rats (n = 60). Global forebrain ischemia
was induced by occlusion of both common carotid arteries in half of the animals.
SDs were triggered by the topical application of 1M KCl. SD occurrence was
confirmed by the acquisition of DC potential, and CBF variations were recorded by
laser-Doppler flowmetry. EP4 receptor antagonism significantly decreased peak
hyperemia and augmented post-SD oligemia in the intact but not in the ischemic
cortex. COX-1 inhibition and EP4 receptor blockade markedly delayed
repolarization after SD in the ischemic but not in the intact brain. COX-2
inhibition achieved no significant effect on any of the end points taken. The
data suggest, that activation of EP4 receptors initiates vasodilation in response
to SD in the intact brain, and - together with COX-1 derived prostanoids -
shortens SD duration in the acute phase of ischemia.
PMID- 27506383
TI - Artificial Control of Gene Silencing Activity Based on siRNA Conjugation with
Polymeric Molecule Having Coil-Globule Transition Behavior.
AB - A new strategy for controlling gene silencing activity of siRNA in the cell was
developed in the present study. siRNA was linearly conjugated with PNIPAAm, where
coil-globule transition of the conjugated PNIPAAm allows thermoresponsive
exposure of the vicinal siRNA molecule; a coil form of PNIPAAm (T < LCST)
inhibits siRNA interaction with gene silencing-related proteins due to the steric
hindrance effect, while a globule form of PNIPAAm (T > LCST) allows a ready
access of siRNA to gene silencing pathway. As a result, at T > LCST, PNIPAAm
siRNA elicited effective association of siRNA with a gene silencing-related
protein of Ago2, while siRNA recruitment into the gene silencing pathway was
significantly suppressed at T < LCST. Ultimately, gene silencing efficacy of
PNIPAAm-siRNA was close to unconjugated siRNA at T > LCST (~80%), while it was
dramatically decreased to ~20% at T < LCST, suggesting that coil-globule
transition of the conjugated polymer can control the bioactivity of the vicinal
siRNA molecule.
PMID- 27506385
TI - Predicting gene targets from integrative analyses of summary data from GWAS and
eQTL studies for 28 human complex traits.
AB - Genome-wide association studies (GWAS) have identified hundreds of genetic
variants associated with complex traits and diseases. However, elucidating the
causal genes underlying GWAS hits remains challenging. We applied the summary
data-based Mendelian randomization (SMR) method to 28 GWAS summary datasets to
identify genes whose expression levels were associated with traits and diseases
due to pleiotropy or causality (the expression level of a gene and the trait are
affected by the same causal variant at a locus). We identified 71 genes, of which
17 are novel associations (no GWAS hit within 1 Mb distance of the genes). We
integrated all the results in an online database (
http://www.cnsgenomics/shiny/SMRdb/ ), providing important resources to
prioritize genes for further follow-up, for example in functional studies.
PMID- 27506384
TI - The neurobiology of the emotional adolescent: From the inside out.
AB - Adolescents are commonly portrayed as highly emotional, with their behaviors
often hijacked by their emotions. Research on the neural substrates of adolescent
affective behavior is beginning to paint a more nuanced picture of how
neurodevelopmental changes in brain function influence affective behavior, and
how these influences are modulated by external factors in the environment. Recent
neurodevelopmental models suggest that the brain is designed to promote emotion
regulation, learning, and affiliation across development, and that affective
behavior reciprocally interacts with age-specific social demands and different
social contexts. In this review, we discuss current findings on neurobiological
mechanisms of adolescents' affective behavior and highlight individual
differences in and social-contextual influences on adolescents' emotionality.
Neurobiological mechanisms of affective processes related to anxiety and
depression are also discussed as examples. As the field progresses, it will be
critical to test new hypotheses generated from the foundational empirical and
conceptual work and to focus on identifying more precisely how and when neural
networks change in ways that promote or thwart adaptive affective behavior during
adolescence.
PMID- 27506386
TI - Once a clinician, always a clinician: a systematic review to develop a typology
of clinician-researcher dual-role experiences in health research with patient
participants.
AB - BACKGROUND: Many health researchers are clinicians. Dual-role experiences are
common for clinician-researchers in research involving patient-participants, even
if not their own patients. To extend the existing body of literature on why dual
role is experienced, we aimed to develop a typology of common catalysts for dual
role experiences to help clinician-researchers plan and implement
methodologically and ethically sound research. METHODS: Systematic searching of
Medline, CINAHL, PsycINFO, Embase and Scopus (inception to 28.07.2014) for
primary studies or first-person reflexive reports of clinician-researchers' dual
role experiences, supplemented by reference list checking and Google Scholar
scoping searches. Included articles were loaded in NVivo for analysis. The coding
was focused on how dual-role was evidenced for the clinician-researchers in
research involving patients. Procedures were completed by one researcher (MB) and
independently cross-checked by another (JHS). All authors contributed to
extensive discussions to resolve all disagreements about initial coding and
verify the final themes. RESULTS: Database searching located 7135 records,
resulting in 29 included studies, with the addition of 7 studies through
reference checks and scoping searches. Two overarching themes described the most
common catalysts for dual-role experiences - ways a research role can involve
patterns of behaviour typical of a clinical role, and the developing connection
that starts to resemble a clinician-patient relationship. Five subthemes
encapsulated the clinical patterns commonly repeated in research settings
(clinical queries, perceived agenda, helping hands, uninvited clinical expert,
and research or therapy) and five subthemes described concerns about the
researcher-participant relationship (clinical assumptions, suspicion and holding
back, revelations, over-identification, and manipulation). Clinician-researchers
use their clinical skills in health research in ways that set up a relationship
resembling that of clinician-patient. Clinicians' ingrained orientation to
patients' needs can be in tension with their research role, and can set up
ethical and methodological challenges. CONCLUSION: The typology we developed
outlines the common ways dual-role is experienced in research involving clinician
researchers and patient-participants, and perhaps the inevitability of the
experience given the primacy accorded to patient well-being. The typology offers
clinician-researchers a framework for grappling with the ethical and
methodological implications of dual-role throughout the research process,
including planning, implementation, monitoring and reporting.
PMID- 27506387
TI - Personality differences in early versus late suicide attempters.
AB - BACKGROUND: Suicidality is an individual behaviour caused by a complex framework
of internal and external factors. The predictive values of personality traits for
a suicide attempt have been demonstrated, especially in conjunction with
Cloninger's TCI and impulsivity. Two issues remain unsolved, namely whether these
traits alter over time after a suicide attempt, and how they may be influenced by
depressive symptoms. METHODS: We studied two patient cohorts: one sample of 81
patients after a suicide attempt no longer than 3 months previously (SA early)
and another sample of 32 patients whose attempt had taken place more than 6
months previously (SA late). We carried out structured interviews with these
subjects addressing diagnosis (MINI), suicidality (Scale for suicide ideation),
depression (HAMD-17), temperament and character inventory (TCI), and impulsivity
(BIS-10). Data analysis was done using SPSS 16.0. RESULTS: Our two groups did not
differ significantly in sociodemographics or suicidality. However, patients in
the SA early group were significantly more depressed (p < 0.001), and scored
lower in reward dependence (p < 0.001) and persistence (p = 0.005) but higher in
harm avoidance (p < 0.001); they did not differ significantly in impulsivity (p <
0.01). Reward dependence, persistence, and harm avoidance remained significantly
different between the two groups after controlling for depressive symptoms.
CONCLUSIONS: Our findings suggest that some personality traits vary after a
suicide attempt. Further investigations are necessary to verify our results,
ideally in longitudinal studies with larger, carefully-described cohorts. It
would be also clinically important to investigate the influence of therapeutic
strategies on the variability of personality traits and their impact on suicidal
behavior.
PMID- 27506388
TI - Grape compounds suppress colon cancer stem cells in vitro and in a rodent model
of colon carcinogenesis.
AB - BACKGROUND: We have previously shown that the grape bioactive compound
resveratrol (RSV) potentiates grape seed extract (GSE)-induced colon cancer cell
apoptosis at physiologically relevant concentrations. However, RSV-GSE
combination efficacy against colon cancer stem cells (CSCs), which play a key
role in chemotherapy and radiation resistance, is not known. METHODS: We tested
the anti-cancer efficacy of the RSV-GSE against colon CSCs using isolated human
colon CSCs in vitro and an azoxymethane-induced mouse model of colon
carcinogenesis in vivo. RESULTS: RSV-GSE suppressed tumor incidence similar to
sulindac, without any gastrointestinal toxicity. Additionally, RSV-GSE treatment
reduced the number of crypts containing cells with nuclear beta-catenin (an
indicator of colon CSCs) via induction of apoptosis. In vitro, RSV-GSE suppressed
- proliferation, sphere formation, nuclear translocation of beta-catenin (a
critical regulator of CSC proliferation) similar to sulindac in isolated human
colon CSCs. RSV-GSE, but not sulindac, suppressed downstream protein levels of
Wnt/beta-catenin pathway, c-Myc and cyclin D1. RSV-GSE also induced mitochondrial
mediated apoptosis in colon CSCs characterized by elevated p53, Bax/Bcl-2 ratio
and cleaved PARP. Furthermore, shRNA-mediated knockdown of p53, a tumor
suppressor gene, in colon CSCs did not alter efficacy of RSV-GSE. CONCLUSION: The
suppression of Wnt/beta-catenin signaling and elevated mitochondrial-mediated
apoptosis in colon CSCs support potential clinical testing/application of grape
bioactives for colon cancer prevention and/or therapy.
PMID- 27506389
TI - Molecular features of biguanides required for targeting of mitochondrial
respiratory complex I and activation of AMP-kinase.
AB - BACKGROUND: The biguanides are a family of drugs with diverse clinical
applications. Metformin, a widely used anti-hyperglycemic biguanide, suppresses
mitochondrial respiration by inhibiting respiratory complex I. Phenformin, a
related anti-hyperglycemic biguanide, also inhibits respiration, but proguanil,
which is widely used for the prevention of malaria, does not. The molecular
structures of phenformin and proguanil are closely related and both inhibit
isolated complex I. Proguanil does not inhibit respiration in cells and
mitochondria because it is unable to access complex I. The molecular features
that determine which biguanides accumulate in mitochondria, enabling them to
inhibit complex I in vivo, are not known. RESULTS: Here, a family of seven
biguanides are used to reveal the molecular features that determine why
phenformin enters mitochondria and inhibits respiration whereas proguanil does
not. All seven biguanides inhibit isolated complex I, but only four of them
inhibit respiration in cells and mitochondria. Direct conjugation of a phenyl
group and bis-substitution of the biguanide moiety prevent uptake into
mitochondria, irrespective of the compound hydrophobicity. This high selectivity
suggests that biguanide uptake into mitochondria is protein mediated, and is not
by passive diffusion. Only those biguanides that enter mitochondria and inhibit
complex I activate AMP kinase, strengthening links between complex I and the
downstream effects of biguanide treatments. CONCLUSIONS: Biguanides inhibit
mitochondrial complex I, but specific molecular features control the uptake of
substituted biguanides into mitochondria, so only some biguanides inhibit
mitochondrial respiration in vivo. Biguanides with restricted intracellular
access may be used to determine physiologically relevant targets of biguanide
action, and for the rational design of substituted biguanides for diverse
clinical applications.
PMID- 27506390
TI - The genome of the emerging barley pathogen Ramularia collo-cygni.
AB - BACKGROUND: Ramularia collo-cygni is a newly important, foliar fungal pathogen of
barley that causes the disease Ramularia leaf spot. The fungus exhibits a
prolonged endophytic growth stage before switching life habit to become an
aggressive, necrotrophic pathogen that causes significant losses to green leaf
area and hence grain yield and quality. RESULTS: The R. collo-cygni genome was
sequenced using a combination of Illumina and Roche 454 technologies. The draft
assembly of 30.3 Mb contained 11,617 predicted gene models. Our phylogenomic
analysis confirmed the classification of this ascomycete fungus within the family
Mycosphaerellaceae, order Capnodiales of the class Dothideomycetes. A predicted
secretome comprising 1053 proteins included redox-related enzymes and
carbohydrate-modifying enzymes and proteases. The relative paucity of plant cell
wall degrading enzyme genes may be associated with the stealth pathogenesis
characteristic of plant pathogens from the Mycosphaerellaceae. A large number of
genes associated with secondary metabolite production, including homologs of
toxin biosynthesis genes found in other Dothideomycete plant pathogens, were
identified. CONCLUSIONS: The genome sequence of R. collo-cygni provides a
framework for understanding the genetic basis of pathogenesis in this important
emerging pathogen. The reduced complement of carbohydrate-degrading enzyme genes
is likely to reflect a strategy to avoid detection by host defences during its
prolonged asymptomatic growth. Of particular interest will be the analysis of R.
collo-cygni gene expression during interactions with the host barley, to
understand what triggers this fungus to switch from being a benign endophyte to
an aggressive necrotroph.
PMID- 27506391
TI - Molecular epidemiology of Mycobacterium africanum in Ghana.
AB - BACKGROUND: Mycobacterium africanum comprises two phylogenetic lineages within
the M. tuberculosis complex (MTBC) and is an important cause of human
tuberculosis (TB) in West Africa. The reasons for this geographic restriction of
M. africanum remain unclear. Here, we performed a prospective study to explore
associations between the characteristics of TB patients and the MTBC lineages
circulating in Ghana. METHOD: We genotyped 1,211 MTBC isolates recovered from
pulmonary TB patients recruited between 2012 and 2014 using single nucleotide
polymorphism typing and spoligotyping. Associations between patient and pathogen
variables were assessed using univariate and multivariate logistic regression.
RESULTS: Of the 1,211 MTBC isolates analysed, 71.9 % (871) belonged to Lineage 4;
12.6 % (152) to Lineage 5 (also known as M. africanum West-Africa 1), 9.2 % (112)
to Lineage 6 (also known as M. africanum West-Africa 2) and 0.6 % (7) to
Mycobacterium bovis. Univariate analysis revealed that Lineage 6 strains were
less likely to be isoniazid resistant compared to other strains (odds ratio =
0.25, 95 % confidence interval (CI): 0.05-0.77, P < 0.01). Multivariate analysis
showed that Lineage 5 was significantly more common in patients from the Ewe
ethnic group (adjusted odds ratio (adjOR): 2.79; 95 % CI: 1.47-5.29, P < 0.001)
and Lineage 6 more likely to be found among HIV-co-infected TB patients (adjOR =
2.2; 95 % confidence interval (CI: 1.32-3.7, P < 0.001). CONCLUSION: Our findings
confirm the importance of M. africanum in Ghana and highlight the need to
differentiate between Lineage 5 and Lineage 6, as these lineages differ in
associated patient variables.
PMID- 27506392
TI - Obstructive sleep apnea is associated with an increased risk of colorectal
neoplasia.
AB - BACKGROUND AND AIMS: A recent meta-analysis showed that obstructive sleep apnea
(OSA) is associated with a higher prevalence of cancer and cancer-related
mortality; however, little information is available on the association between
OSA and colorectal neoplasia. METHODS: We identified consecutive patients who
underwent overnight polysomnography (PSG) and subsequent colonoscopy. We compared
the prevalence of colorectal neoplasia between patients with or without OSA
according to the results of PSG. For each patient with OSA, 1 or 2 controls
matched for age (+/-5 years), sex, body mass index (BMI), and smoking who had
undergone first-time screening colonoscopy were selected. RESULTS: Of the 163
patients, 111 patients were diagnosed with OSA and 52 patients were within the
normal range of the Apnea-Hypopnea Index. Of the 111 patients with OSA, 18
patients (16.2%) had advanced colorectal neoplasia, including 4 (3.6%) colorectal
cancers. In the multivariate analyses, OSA was associated with an increased risk
of advanced colorectal neoplasia after adjusting for factors including age and
sex (mild: odds ratio [OR], 14.09; 95% confidence interval [CI], 1.55-127.83; P =
.019; moderate or severe: OR, 14.12; 95% CI, 1.52-131.25; P = .020). Our case
control study revealed that the odds of detecting advanced colorectal neoplasia
among patients with OSA were approximately 3.03 times greater than in the
controls matched for age, sex, BMI, and smoking (OR, 3.03; 95% CI, 1.44-6.34; P =
.002). CONCLUSION: Physicians should be aware of the association between OSA and
the development of colorectal neoplasia and explain the need for colonoscopy to
patients with OSA.
PMID- 27506393
TI - Non-adherence to the rule of 3 does not increase the risk of adverse events in
esophageal dilation.
AB - BACKGROUND AND AIMS: Although the rule of 3 is recommended to minimize the risk
of perforation when esophageal dilation is performed using bougie dilators, there
are no data to validate its use. Our aim was to investigate the association
between the rule of 3 and adverse events (AEs) in esophageal dilation. METHODS: A
retrospective chart review in patients who underwent esophageal bougie or balloon
dilation between December 1991 and February 2013 at a tertiary hospital was
performed. Data collection included patient demographics, stricture and
procedural characteristics, AEs, and follow-up. Univariate logistic regression
models were used to assess the risk of AEs and perforations. RESULTS: A total of
297 patients (median age, 63 years; 60% men) underwent 2216 esophageal bougie or
balloon dilations. Major AEs occurred in 22 (1%) dilation sessions, including 11
(0.5%) perforations, 4 (0.2%) fistulas, 3 (0.1%) hospitalizations for pain
management, 2 (0.09%) clinically significant hemorrhages, 1 (0.04%) fever, and 1
(0.04%) tracheoesophageal voice prosthesis leak. Mean duration of treatment was
43.2 months (standard deviation, 47.7 months). Most strictures were benign (n =
275; 93%) and complex in nature (n = 198; 67%). Non-adherence to the rule of 3
occurred in 190 (13%) dilations with bougie dilators. Non-adherence was not
associated with a higher rate of major AEs (1/190, 0.5% vs 15/953, 1.6%; P = .18)
and perforations (0/190, 0% vs 7/952, 0.7%; P = .18). Gender, complex strictures,
location of the stricture, type of dilator, and additional interventions were
also not associated with major AEs or perforations. However, malignant strictures
were associated with an increased risk of major AEs (odds ratio, 3.5; 95%
confidence interval, 1.1-12.0) and perforations (odds ratio, 8.3; 95% confidence
interval, 2.2-31.9). CONCLUSIONS: Non-adherence to the rule of 3 does not appear
to increase the risk of AEs, particularly perforation, after esophageal dilation
using bougie dilators. Caution is needed with the dilation of malignant
strictures, as there is an increased risk of perforations and AEs. However, large
prospective studies are needed to verify the results of this study.
PMID- 27506394
TI - A personalised approach is needed for the management of non-tuberculous
mycobacterial cervicofacial lymphadenitis.
PMID- 25475648
TI - Acute diverticulitis of the terminal ileum: ultrasonography and CT findings.
AB - We describe a rare case of terminal ileal diverticulitis in a 68-year-old female
with a day of history of right lower quadrant pain and tenderness, mimicking
acute appendicitis. Ultrasonography revealed small sac-like out-pouching lesions
with increased echogenicity of surrounding fat in thickened terminal ileum,
suggesting inflamed diverticula. We diagnosed terminal ileal diverticulitis
primarily by ultrasonography. The diagnosis was confirmed by subsequent computed
tomography.
PMID- 27506395
TI - Pneumonia presenting with organ dysfunctions: Causative microorganisms, host
factors and outcome.
AB - Community-acquired pneumonia (CAP) is a serious infection that may occasionally
rapidly evolve provoking organ dysfunctions. We aimed to characterize CAP
presenting with organ dysfunctions at the emergency room, with regard to host
factors and causative microorganisms, and its impact on 30-day mortality. 460 of
4070 (11.3%) CAP patients had >=2 dysfunctions at diagnosis, with a 30-day
mortality of 12.4% vs. 3.4% in those with one or no dysfunctions. Among them, the
most frequent causative microorganisms were Streptococcus pneumoniae, gram
negatives and polymicrobial etiology. Independent host risk factors for
presenting with >=2 dysfunctions were: liver (OR 2.97) and renal diseases (OR
3.91), neurological disorders (OR 1.86), and COPD (OR 1.30). Methicillin
resistant Staphylococcus aureus (OR 6.41) and bacteraemic episodes (OR 1.68) had
the higher independent risk among microorganisms. The number of organ
dysfunctions vs. none increased at 30-day mortality: three organs (OR 11.73), two
organs (OR 4.29), and one organ (OR 2.42) whereas Enterobacteria (OR 3.73) were
also independently related to mortality. The number of organ dysfunctions was the
strongest 30-day mortality risk factor while Enterobacteriaceae was also
associated with poorer outcome. The assessment of organ dysfunctions in CAP
should be implemented for management, allocation and treatment decisions on
initial evaluation.
PMID- 27506397
TI - Characterization of the excited states of DNA building blocks: a coupled cluster
computational study.
AB - DNA building blocks consisting of up to four nucleobases are investigated using
the EOM-CCSD and CC2-LR methods in two B-DNA-like arrangements of a poly
adenine:poly-thymine (poly-A:poly-T) system. Excitation energies and oscillator
strengths are presented and the characteristics of the excited states are
discussed. Excited states of single-stranded poly-A systems are highly
delocalized, especially the spectroscopically bright states, where delocalization
over up to four fragments can be observed. In the case of poly-T systems, the
states are somewhat less delocalized, extending to maximally about three
fragments. A single A:T Watson-Crick pair has highly localized states, while
delocalization over base pairs can be observed for some excited states of the
(A)2:(T)2 system, but intrastrand delocalization is more pronounced in this case,
as well. As for the characteristics of the simulated UV absorption spectra, a
significant decrease of intensity can be observed in the case of single strands
with increasing chain length; this is due to the stacking interactions and is in
accordance with previous results. On the other hand, the breaking of H-bonds
between the two strands does not alter the spectral intensity considerably, it
only causes a redshift of the absorption band, thus it is unable to explain the
experimentally observed DNA hyperchromism on its own, and stacking interactions
need to be considered for the description of this effect as well.
PMID- 27506398
TI - Fluorination methods in drug discovery.
AB - Fluorination reactions of medicinal and biologically-active compounds will be
discussed. Late stage fluorination strategies of medicinal targets have recently
attracted considerable attention on account of the influence that a fluorine atom
can impart to targets of medicinal importance, such as modulation of
lipophilicity, electronegativity, basicity and bioavailability, the latter as a
consequence of membrane permeability. Therefore, the recourse to late-stage
fluorine substitution on compounds with already known and relevant biological
activity can provide the pharmaceutical industry with new leads with improved
medicinal properties. The fluorination strategies will take into account
different fluorinating reagents, either of nucleophilic or electrophilic, and of
radical nature. Diverse families of organic compounds such as (hetero)aromatic
rings, and aliphatic substrates (sp(3), sp(2), and sp carbon atoms) will be
studied in late-stage fluorination reaction strategies.
PMID- 27506399
TI - Evaporation of Binary Sessile Drops: Infrared and Acoustic Methods To Track
Alcohol Concentration at the Interface and on the Surface.
AB - Evaporation of droplets of three pure liquids (water, 1-butanol, and ethanol) and
four binary solutions (5 wt % 1-butanol-water-based solution and 5, 25, and 50 wt
% ethanol-water-based solutions) deposited on hydrophobic silicon was
investigated. A drop shape analyzer was used to measure the contact angle,
diameter, and volume of the droplets. An infrared camera was used for infrared
thermal mapping of the droplet's surface. An acoustic high-frequency echography
technique was, for the first time, applied to track the alcohol concentration in
a binary-solution droplet. Evaporation of pure alcohol droplets was executed at
different values of relative humidity (RH), among which the behavior of pure
ethanol evaporation was notably influenced by the ambient humidity as a result of
high hygrometry. Evaporation of droplets of water and binary solutions was
performed at a temperature of 22 degrees C and a mean humidity of approximately
50%. The exhaustion times of alcohol in the droplets estimated by the acoustic
method and the visual method were similar for the water-1-butanol mixture;
however, the time estimated by the acoustic method was longer when compared with
that estimated by the visual method for the water-ethanol mixture due to the
residual ethanol at the bottom of the droplet.
PMID- 27506400
TI - A Novel Less Invasive Technique for the Excision of Large Intradural and
Extradural Dumbbell Lumbar Schwannomas: The "Dual Approach".
AB - OBJECTIVE: Large schwannomas with intradural and extradural extensions are often
challenging surgical lesions. A variety of approaches, usually requiring large
exposures, removal of facets and pars interarticularis, and spinal stabilization,
have been described. The aim of this study is to describe the "dual approach," a
less invasive technique for the excision of these lesions. METHODS: A large
intradural and extradural schwannoma with paraspinal extension (Eden type II) was
removed by a unilateral approach-midline, pars and facet sparing and no
supplemental instrumentation. RESULTS: Complete excision was achieved through the
described approach, with minimal removal of bone and soft tissue disruption.
There were no intraoperative or perioperative complications and no evidence of
residual tumor or instability/deformity. CONCLUSIONS: The dual approach is a
novel and unique technique that allows complete and safe removal of large
intradural and extradural dumbbell tumors through a less invasive approach and no
need for instrumentation.
PMID- 27506401
TI - Standalone Anterior Cervical Discectomy and Fusion Versus Combination with
Foraminotomy for the Treatment of Cervical Spondylotic Radiculopathy Secondary to
Bony Foraminal Stenosis.
AB - OBJECTIVE: To compare the results of anterior cervical discectomy and fusion
(ACDF) combined with anterior cervical foraminotomy (ACF) and standalone ACDF for
the treatment of cervical spondylotic radiculopathy (CSR). METHODS: The data of
24 consecutive patients who underwent ACDF combined with ACF for significant bony
foraminal stenosis were reviewed. The clinical outcomes, including visual analog
scale (VAS) scores for neck pain and arm pain and Neck Disability Index, were
evaluated by questionnaires. Radiologic outcomes as manifested by C2-7 angle and
surgical segmental angle were recorded. The outcomes were compared with outcomes
of standalone ACDF for CSR secondary to posterolateral spurs. RESULTS: At the
final follow-up evaluation, all patients obtained bone fusion. No patient
developed adjacent segment disease. Operative time was longer and blood loss was
more in the ACDF combined with ACF group than in the ACDF group (all P < 0.05).
However, in both groups, the neck VAS score, arm VAS score, and Neck Disability
Index were significantly reduced postoperatively (all P < 0.05). The segmental
curve and C2-7 lordosis were significantly improved postoperatively (all P <
0.05). There was no significant difference between the 2 groups in clinical and
radiologic outcomes (P > 0.05). CONCLUSIONS: For CSR with foraminal stenosis
secondary to significant bony pathology that cannot be managed with standalone
ACDF, ACDF combined with ACF is an effective and safe treatment strategy.
PMID- 27506402
TI - Choroid Plexus Papillomas of the Cerebellopontine Angle.
AB - OBJECTIVE: Choroid plexus papillomas (CPPs) of the cerebellopontine angle (CPA)
are extremely rare. We present a series of 21 cases operated on in the last 7
years at our institution. METHODS: During the period from January 2008 to October
2015, we encountered 102 histologically established cases of CPPs, of which 21
were located in the CPA region. Clinical profiles, radiologic features, surgical
procedures, intraoperative findings, and outcomes were extracted from the patient
records and neuroimaging data. RESULTS: The 21 CPPs in the CPA region accounted
for 20.5% of all CPPs. Two of the tumors occurred in pediatric patients. Tumor
size was 2.5-4.7 cm. The rate of calcification was higher in the CPPs in the CPA
region. Peritumoral cysts and cysts with small nodules were observed in our
cases. A far lateral suboccipital approach was chosen for CPPs protruding
inferiorly into the foramen magnum region (n = 14), and a suboccipital
retrosigmoid approach was chosen for the other tumors. Total resection was
achieved in 18 patients, and subtotal resection was achieved in 3 patients.
During the follow-up period, only 1 patient experienced recurrence 32 months
after the first operation. The recurrence turned out to be an atypical CPP.
CONCLUSIONS: CPPs in the CPA region cannot be easily differentiated from other
tumors preoperatively. Cysts and calcifications appear on neuroimaging. CPPs in
the CPA region usually protrude inferiorly into the foramen magnum region. As
much tumor should be removed as possible to avoid recurrence and malignant
transition.
PMID- 27506403
TI - Risk Factors for Dysphagia After Single-Level Anterior Cervical Decompression
with Arthroplasty or Fusion: A Prospective Study Comparing 2 Zero-Profile
Implants.
AB - OBJECTIVE: To determine any differences in self-reported dysphagia in patients
treated with single-level anterior cervical decompression with different zero
profile implants (arthroplasty vs. arthrodesis) and identify risk factors for
postoperative dysphagia. METHODS: A total of 112 patients with 1-level cervical
degenerative disc disease were included in the prospective study. The dysphagia
conditions and radiologic results were assessed using Bazar dysphagia scoring
system, the Swallowing Quality of Life scores, cervical alignment (CA), segmental
angle, and prevertebral soft tissues swelling (PSTS). All these parameters were
compared before and after surgery in the respective group, which were also
compared between the 2 groups. Correlations between the confounding factors and
postoperative dysphagia were analyzed. RESULTS: No significant differences
existed in preoperative or initially postoperative dysphagia rate and scores
between the 2 groups (P > 0.05). However, the dysphagia rate and scores of
cervical disc arthroplasty was better than those of fusion at postoperative day
7. Heavy smoker, PSTS change (>=5 mm), or CA change (>=5 degrees) was prone to
have postoperative dysphagia. CONCLUSIONS: Postoperative dysphagia remains a
common incidence, despite advances in instrumentation technologies. However,
cervical disc arthroplasty is superior to anterior cervical discectomy and fusion
in ameliorating the symptom of dysphagia in the early postoperative term. Heavy
smoker, PSTS change (>=5 mm), and CA change (>=5 degrees) were important
predictors of postoperative dysphagia.
PMID- 27506404
TI - Open Surgery for Recurrent Intracranial Aneurysms: Techniques and Long-Term
Outcomes.
AB - BACKGROUND: After occlusion of an aneurysm, a patient may experience aneurysm
regrowth at the same site or develop de novo aneurysms. We present our experience
in microsurgery of recurrent aneurysms with analysis of long-term results.
METHODS: The senior authors (R. T. and H. K.) performed recurrent aneurysm
clipping on 44 patients at Teishinkai Hospital and Asahikawa Red Cross Hospital
in Sapporo, Japan. Operative techniques included clipping only, clipping and
protective bypass, trapping of aneurysm with bypass, proximal occlusion, and
bypass. Postoperative outcome was analyzed retrospectively using the modified
Rankin Scale. RESULTS: Our series included 10 men (23%) and 34 women (77%), with
a mean patient age of 63 years (range, 7-82 years). Before primary treatment, 11
patients (25%) had a ruptured aneurysm, while 33 patients (75%) had an unruptured
aneurysm. The mean follow-up time after primary surgery was 7.6 years (range, 0.8
25 years). At our department the treatment of recurrent aneurysm included the
clipping in 19 patients (43%), clipping with bypass in 6 patients (14%), aneurysm
trapping with bypass in 10 patients (23%), and proximal occlusion and bypass in 9
patients (20%). The mean follow-up time after surgical treatment of recurrent
aneurysms stood at 3.5 years (range 0.1-9 years). Altogether, 37 patients (84%)
experienced favorable outcomes at last follow-up examination (modified Rankin
Scale scores 0 and 1). CONCLUSIONS: Microsurgery of recurrent aneurysms may be
performed safely and effectively, as shown by our study, in which 84% of patients
experienced favorable results.
PMID- 27506405
TI - Management Strategy of a Transorbital Penetrating Pontine Injury by a Wooden
Chopstick.
AB - BACKGROUND: Transorbital penetrating pontine injuries from small spear-like
objects, which are extremely rare, provide neurosurgeons with life-threatening
and challenging conditions to manage. CASE DESCRIPTION: We present an unusual
case of transorbital penetrating pontine injury and discuss imaging, diagnosis,
management strategy, and anatomy-injury correlation. A 23-year-old man sustained
a penetrating cranial injury from a bamboo chopstick that extended from the right
orbit to the pons and cerebellum. Using a frontotemporal approach, we
successfully removed the chopstick. Follow-up studies confirmed a good outcome.
CONCLUSIONS: Preoperative imaging, correct diagnosis, and surgical treatment are
necessary to manage transorbital penetrating pontine injuries caused by spear
like objects, with specific attention paid to effective exposure and inventive
means with total removal of the foreign object without causing further injury. A
trajectory through the superior orbital fissure and paralateral to the cavernous
sinus and into the pons seems to be the most prevalent and influences management
of removal and injuries.
PMID- 27506406
TI - Differences in Dural Penetration of Clival Chordomas Are Associated with
Different Prognosis and Expression of Platelet-Derived Growth Factor Receptor
beta.
AB - OBJECTIVE: We sought to compare the prognosis of clival chordomas with different
dural penetration and establish the relationship between dural penetration and
platelet-derived growth factor receptor (PDGFR)-beta signaling pathway. METHODS:
Tumors in Type I (33 cases) showed limited dural penetration, while those in Type
II (34 cases) had more serious dural penetration. Cox multivariate regression
analysis was used to analyze risk factors affecting survival. Kaplan-Meier
analysis measured overall survival (OS) and progression-free survival (PFS). To
determine the relationship between dural penetration and PDGFR-beta signaling,
expression of PDGFR-beta, Akt, mammalian target of rapamycin (mTOR), and
phosphatase and tensin homolog (PTEN) expression was compared using
immunohistochemistry, quantitative reverse transcription polymerase chain
reaction, and Western blotting. RESULTS: Total resection was achieved in 9 cases
in Type I and 11 in Type II. There were significant correlations between OS and
dural penetration (P = 0.032) and age (P = 0.034). PFS correlated significantly
with dural penetration (P = 0.022), gender (P = 0.001), and degree of resection
(P = 0.001). Mean OS in Type I was significantly longer than in Type II (P =
0.046). Patients aged <55 years had longer OS than those aged >=55 years (P =
0.004). Total resection was correlated with longer PFS (P = 0.011). Among
patients with tumors totally resected, mean PFS in Type I was significantly
longer than in Type II (P = 0.007). Expression of PDGFR-beta in Type II was
higher than in Type I. CONCLUSIONS: Clival chordomas have different degrees of
dural penetration. Patients with chordomas with serious dural penetration have
poorer prognosis. Higher expression of PDGFR-beta is related to more serious
dural penetration of clival chordomas.
PMID- 27506407
TI - Barriers to Neurosurgical Training in Sub-Saharan Africa: The Need for a Phased
Approach to Global Surgery Efforts to Improve Neurosurgical Care.
AB - BACKGROUND: Neurosurgery in low-income countries is faced with multiple
challenges. Although the most common challenges include infrastructure and
physical resource deficits, an underemphasized barrier relates to the methods and
components of surgical training. The role of important aspects, including
didactic surgical training, surgical decision-making, workshops, conferences, and
assessment methods, has not been duly studied. Knowledge of these issues is a
crucial step to move closer to strengthening surgical capacity in low-income
countries. METHODS: We designed an online survey to assess self-perceived and
objectively measured barriers to neurosurgical training in various Sub-Saharan
African countries. Key outcomes included perception toward adequacy of
neurosurgery training and barriers to neurosurgical training at each individual
site. RESULTS: Only 37% of responders felt that their training program adequately
prepared them for handling incoming neurosurgical cases. Top perceived
limitations of neurosurgery training included lack of physical resources (25% of
all responses), lack of practical workshops (22%), lack of program structure
(18%), and lack of topic-specific lectures (10%). CONCLUSIONS: Our results show
that most responders believe their training program is inadequate and are
interested in improving it through international collaborations. This implies
that activities directed at strengthening surgical capacity must address this
important necessity. One important strategy is the use of online educational
tools. In consideration of the observed limitations in care, resources, and
training, we recommend a phased approach to neurosurgical growth in low-income
settings.
PMID- 27506408
TI - Powder Topical Rifampin for Reducing Infections After Neural Tube Defect Surgery
in Infants.
AB - OBJECTIVE: The correct timing and technique of neural tube defect (NTD) repairs
significantly decrease the morbidity and mortality of NTD cases. However,
infections related to the surgery are still common. We investigated the effects
of topical rifampin combined with routine prophylaxis in newborns with open NTDs.
METHODS: This retrospective study included 86 patients who had undergone NTD
surgery. The experimental group comprised 30 patients who were started on topical
rifampin before surgery, and the control group comprised 56 patients who were not
administered topical rifampin. Surgical site infections (SSIs) and
meningitis/ventriculoperitoneal (VP) shunt infections that developed within 6
months after the surgical intervention were evaluated. RESULTS: In the
postoperative period, meningitis/VP shunt infections and SSIs were observed in
6.7% and 3.3%, respectively, of the experimental group treated with topical
rifampin. Meningitis/VP shunt infections and SSIs were observed in 37.5% and
21.4%, respectively, of the control group. External ventricular drainage and not
using topical rifampin were identified as important relative risk (RR) factors
for meningitis/VP shunt infections (RR 19.28, 95% confidence interval [CI] [3.53,
105.33], P = 0.001; RR 18.10, 95% CI [2.38, 137.68], P = 0.005). A flap
transposition, cerebrospinal fluid leaks, and not using topical rifampin were
identified as RR factors for SSIs (RR 22.21, 95% CI [4.81, 102.47], P < 0.001; RR
13.04, 95% CI [1.22, 139.33], P = 0.034; RR 7.09, 95% CI [1.12, 53.99], P =
0.042). We did not observe any local or systemic side effects resulting from the
use of rifampin. CONCLUSIONS: The use of topical rifampin is an easy and
effective method for reducing SSIs and meningitis/VP shunt infections related to
NTD surgery.
PMID- 27506409
TI - Assessing Barriers to Neurosurgical Care in Sub-Saharan Africa: The Role of
Resources and Infrastructure.
AB - BACKGROUND: Quantitative estimates of surgical capacity and infrastructure and
perceived care limitations in low-resource countries are essential baseline
measures that can provide strategies for improving access to surgical care.
Information about these barriers in Africa is scarce, particularly with respect
to neurosurgery. We conducted a survey to better understand the unmet surgical
need and resources available for the care of neurosurgery patients in Sub-Saharan
Africa. METHODS: Using SurveyMonkey, we administered a neurosurgery-specific
survey to neurosurgery attending surgeons and residents in Sub-Saharan African
countries. Key outcome measures included workforce, access to imaging modalities
and instruments, volume and breakdown of neurosurgical cases, and perceived
limitations of care. RESULTS: We obtained a 41% survey response (129/314 sent).
In addition to the expected large gap in workforce between low- and high-income
countries, we found a dramatic paucity of neurosurgical resources in Central
Africa, whereas specific pockets in West and South Africa have better
neurosurgical care. Access to neuroimaging was not a major limitation in Sub
Saharan African countries. The most commonly perceived limitations of care
included infrastructure, anesthesia/nursing availability, wait times, and
strength of training. CONCLUSIONS: This large survey defines important self
perceived limitations to care within neurosurgery and highlights the importance
of infrastructure and allied professions in this role. A clear understanding of
areas of focus will enable a more efficient and sustainable response to the
limitations in surgical care in low-resource areas.
PMID- 27506410
TI - When the Infection Hits the Wound: Matched Case-Control Study in a Neurosurgical
Patient Collective Including Systematic Literature Review and Risk Factors
Analysis.
AB - BACKGROUND: To avoid surgical site infections (SSIs) by identifying patients at
high risk for infectious complications, a better understanding of relevant risk
factors is required. This manuscript describes a matched case-control study of
patients undergoing cranial neurosurgery with postoperative surgical site
infections and a systematic literature review. METHODS: From January 2012 to
March 2015, 70 patients (2.47%) with SSIs (out of 2819 patients) and 185 controls
were identified. Statistical analyses were performed using univariate and
multivariate models to identify risk factors associated with SSIs. RESULTS: The
time of the onset of SSIs ranged from 8 to 854 days after surgery (median: 42
days). American Society of Anesthesiologists score (P = 0.003), surgical drain (P
<0.001), number of previous operations (P <0.001), and implantation of foreign
material (P <0.001) were significant risk factors for SSIs in multivariate
analysis. In a systematic literature review, the authors identified 20
independent risk factors. CONCLUSIONS: This article provides information to ease
the prospective assessment of patients at risk of SSI based on preoperative and
postoperative risk factors. Lowering the incidence of SSIs will improve the
patient outcomes and the overall quality of the healthcare delivered. To our
knowledge, this is the first systemic literature review of SSIs in cranial
neurosurgery and analysis of own cases in a wide spectrum.
PMID- 27506412
TI - Why do maternal and newborn deaths continue to occur?
AB - According to estimates in 2015, there were 303,000 maternal deaths, 2.7 million
newborn deaths and 2.6 million stillbirths. A wide range of factors, from health
system dynamics to social determinants of health and underlying health
conditions, contribute to this outcome. The highest mortality risk for mothers
and their babies is on the day of birth, and most of these deaths are
preventable. The largest burden of deaths occurs in low-income countries,
particularly in sub-Saharan Africa and South Asia, due to their young population
and high fertility. Substantial reductions in maternal and newborn mortality have
been achieved between 1990 and 2015, but it has not been fast enough and
stillbirths continue to remain uncounted in many national vital statistics
systems. Lack of a universal definition and classification system for stillbirths
is an obstacle for preventing stillbirths, hindering the design of effective
interventions.
PMID- 27506414
TI - Chelating bis-N-heterocyclic carbene complexes of iron(ii) containing bipyridyl
ligands as catalyst precursors for oxidation of alcohols.
AB - Chelating bis-N-heterocyclic carbene (bis-NHC) complexes of iron(ii) containing
pyridyl ligands have been prepared by the reaction of [FeCl2L] [L = bipy (1),
phen (2)] with [LiN(SiMe3)2] and a bis(imidazolium) salt. The [Fe(bis-NHC)L(I)2]
complexes were active pre-catalysts in the oxidation of 1-phenylethanol with tert
butyl hydroperoxide in neat conditions, affording a quantitative yield of
acetophenone in 4.5 h. The catalyst could be reused up to six cycles giving a
turnover number (TON) of 1500. Various secondary alcohols, both aromatic and
aliphatic were selectivity oxidised to the corresponding ketones in excellent
yields. Compound 1 is stable in acetonitrile solution for ca. 4 h, although after
16 h, it evolves to a mixture of [Fe(bis-NHC)(bipy)2]I2 (3), [Fe(bipy)3](2+) and
bis-imidazolium salt. The molecular structure of 3 has been determined by X-ray
diffraction studies.
PMID- 27506413
TI - Sequence determinants of subtype-specific actions of KCNQ channel openers.
AB - KEY POINTS: Retigabine is a KCNQ voltage-gated potassium channel opener that was
recently approved as an add-on therapeutic for patients with drug-resistant
epilepsy. Retigabine exhibits very little specificity between most KCNQ channel
subtypes, and there is interest in generating more potent and specific KCNQ
channel openers. The present study describes the marked specificity of ICA069673
for KCNQ2 vs. KCNQ3, and exploits this property to investigate determinants of
KCNQ subtype specificity. ICA069673 acts on a binding site in the voltage-sensing
domain that is distinct from the putative retigabine site in the channel pore.
ICA069673 has two separable effects on KCNQ channel activity. We identify two
channel residues required for subtype specificity of KCNQ channel openers and
show that these are sufficient to generate ICA069673 sensitivity in KCNQ3.
ABSTRACT: Retigabine (RTG) is the first approved anti-epileptic drug that acts
via activation of voltage-gated potassium channels, targeting KCNQ channels that
underlie the neuronal M-current. RTG exhibits little specificity between KCNQ2-5
as a result of conservation of a Trp residue in the pore domain that binds to the
drug. The RTG analogue ICA-069673 ('ICA73') exhibits much stronger effects on
KCNQ2 channels, including a large hyperpolarizing shift of the voltage-dependence
of activation, an ~2-fold enhancement of peak current and pronounced subtype
specificity for KCNQ2 over KCNQ3. Based on ICA73 sensitivity of chimeric
constructs of the transmembrane segments of KCNQ2 and KCNQ3, this drug appears to
interact with the KCNQ2 voltage sensor (S1-S4) rather than the pore region
targeted by RTG. KCNQ2 point mutants in the voltage sensor were generated based
on KCNQ2/KCNQ3 sequence differences, and screened for ICA73 sensitivity. These
experiments reveal that KCNQ2 residues F168 and A181 in the S3 segment are
essential determinants of ICA73 subtype specificity. Mutations at either position
in KCNQ2 abolish the ICA73-mediated gating shift, but preserve RTG sensitivity.
Interestingly, A181P mutant channels show little ICA73-mediated gating shift but
retain current potentiation by the drug. Mutations (L198F and P211A), which
introduce these critical KCNQ2 residues at corresponding positions in KCNQ3,
transplant partial ICA73 sensitivity. These findings demonstrate that RTG and
ICA73 act via distinct mechanisms, and also reveal specific residues that
underlie subtype specificity of KCNQ channel openers.
PMID- 27506415
TI - Short-term versus longer duration of glucocorticoid therapy for exacerbations of
chronic obstructive pulmonary disease.
AB - BACKGROUND: Systemic glucocorticoid has been shown to improve the outcome of
acute exacerbation of chronic obstructive pulmonary disease (COPD). However, the
optimal duration remains controversial. OBJECTIVES: To investigate whether a
short-term (seven days or fewer) systemic glucocorticoid treatment in patients
with COPD exacerbation is non inferior to longer duration (more than seven days)
treatment in clinical outcome. METHODS: We searched PubMed, EMBASE, CENTRAL
databases, China Clinical Trials, CNKI, The Chinese biomedical literature
database (CBM) and wanfang database to identify randomized controlled trials
using systemic glucocorticoid in COPD. At least two review authors independently
assessed each potentially eligible trial for its inclusion in the review and its
quality. Glucocorticoid is given for a period of seven days or fewer versus
systemic given for more than seven days. We retrieved time from building to Apr
20, 2016, and supplemented by manual retrieval into literature references. By
adopting the combination of keywords and free word retrieval methods, we
performed a routine meta-analysis to evaluate the effects of glucocorticoid on
FEV1, FEV1/FVC, PaO2, clinical symptoms, relapse, treatment failure, mortality
and side-effects between the two treatment groups. RESULTS: Our search yielded 9
studies involving 874 patients. Six studies were fully published and three were
published as abstracts. We obtained data for one study published as abstracts
from authors. Short-term treatment varied between three and seven days and longer
duration 10-15 days, at equivalent daily doses of glucocorticoid. Mean ages of
participants ranged from 60 to 90 years. The FEV1, FEV1/FVC, PaO2 and clinical
symptoms between the two treatment groups did not differ significantly by
treatment duration. There was no significant difference of relapse, treatment
failure, mortality and side-effects between the two treatment groups. CONCLUSION:
These data show that short-term glucocorticoid is as effective as and possibly
safer than longer duration.
PMID- 27506416
TI - Extracellular vesicle-driven information mediates the long-term effects of
particulate matter exposure on coagulation and inflammation pathways.
AB - BACKGROUND: Continuous exposure to particulate air pollution (PM) is a serious
worldwide threat to public health as it coherently links with increased morbidity
and mortality of cardiorespiratory diseases (CRD), and of type 2 diabetes (T2D).
Extracellular vesicles (EVs) are circular plasma membrane fragments released from
human cells that transfer microRNAs between tissues. In the present work it was
explored the hypothesis that EVs with their encapsulated microRNAs (EVmiRNAs)
contents might mediate PM effects by triggering key pathways in CRD and T2D.
METHODS: Expression of EVmiRNAs analyzed by real-time PCR was correlated with
oxidative stress, coagulation and inflammation markers, from healthy steel plant
workers (n=55) with a well-characterized exposure to PM and PM-associated metals.
All p-values were adjusted for multiple comparisons. In-silico Ingenuity Pathway
Analysis (IPA) was performed to identify biological pathways regulated by PM
associated EVmiRNAs. RESULTS: Increased expression in 17 EVmiRNAs is associated
with PM and metal exposure (p<0.01). Mir-196b that tops the list, being related
to 9 different metals, is fundamental in insulin biosynthesis, however three (miR
302b, miR-200c, miR-30d) out of these 17 EVmiRNAs are in turn also related to
disruptions (p<0.01) in inflammatory and coagulation markers. CONCLUSIONS: The
study's findings support the hypothesis that adverse cardiovascular and metabolic
effects stemming from inhalation exposures in particular to PM metallic component
may be mediated by EVmiRNAs that target key factors in the inflammation,
coagulation and glucose homeostasis pathways.
PMID- 27506417
TI - Neonatal isoflavone exposure interferes with the reproductive system of female
Wistar rats.
AB - There is increasing concern about possible adverse effects of soy based infant
formulas (SBIF) due to their high amount of isoflavones (ISO). The aim of the
present study was to investigate effects of neonatal exposure to ISO on
reproductive system of female Wistar rats. Animals were exposed to an ISO
depleted diet or a diet enriched with an ISO extract (IRD; 508mg ISO/kg) during
embryogenesis and adolescence. Pups of each group were fed daily by pipette with
ISO-suspension (ISO+; 32mg ISO/kg bw) or placebo from postnatal day (PND) 1 until
PND23 resulting in plasma concentrations similar to levels reported in infants
fed SBIF. The visceral fat mass was reduced by long-term IRD. Vaginal epithelial
height was increased at PND23 and vaginal opening was precocious in ISO+ groups.
Later in life, more often irregular estrus cycles were observed in rats of ISO+
groups. In addition, FSH levels and uterine epithelial heights were increased at
PND80 in ISO+ groups. In summary, the results indicate that neonatal ISO intake,
resulting in plasma concentrations achievable through SBIF, has an estrogenic
effect on prepubertal rats and influences female reproductive tract later in
life.
PMID- 27506418
TI - Paradoxical effect of methimazole on liver mitochondria: In vitro and in vivo.
AB - Methimazole is the most frequently prescribed antithyroid agent. On the other
hand, several cases of liver injury are attributed to this drug. The mechanism of
methimazole-induced liver injury is obscure. Hepatocytes mitochondria seem to be
a target for methimazole cytotoxicity. Current investigation aimed to evaluate
the effects of methimazole on the hepatocytes mitochondria in different
experimental models. In the in vivo model, methimazole (100, 200 and 400mg/kg,
i.p) was administered to mice and liver mitochondria were isolated and assessed.
In the in vitro experiments, intact isolated liver mitochondria were incubated
with increasing methimazole concentrations (10MUM-100mM). It was found that
methimazole decreased liver mitochondrial ATP and glutathione, increased
mitochondrial swelling, lipid peroxidation and reactive oxygen species (ROS), and
collapsed mitochondrial membrane potential when administered to mice.
Paradoxically, methimazole not only caused no significant injury toward isolated
liver mitochondria in vitro but improved mitochondrial function and protected
this organelle. The differences between two investigated models in the current
study might be associated with drug bioactivation and reactive metabolites
formation. These findings suggest mitochondrial dysfunction as a mechanism for
methimazole-induced liver injury. Moreover, methimazole seems to be a novel
mitochondrial protecting agent in vitro.
PMID- 27506419
TI - New brominated flame retardants and their metabolites as activators of the
pregnane X receptor.
AB - The present study investigated the activities on different nuclear receptors of
the new brominated flame retardants 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB)
and bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH), and their main
carboxylic acid metabolites 2,3,4,5-tetrabromobenzoic acid (TBBA) and mono(2
ethylhexyl) tetrabromophthalate (TBMEPH). None of selected chemicals exhibited
marked activity towards PPARalpha and PPARgamma by the use of transactivation
assays in HepG2 cells transfected with peroxisome proliferator-activated
receptors. In contrast, selected flame retardants all exhibited potent agonist
activity on pregnane X receptor (PXR), with EC50 values of 5.5MUM for TBPH and
2.0MUM for its metabolite TBMEPH. Molecular docking of TBPH and TBMEPH to the PXR
ligand binding site revealed similar interactions, with differences only for
conformation and orientation of the alkyl chains. Additionally, TBPH showed
antagonist activity on PXR (IC50, 13.9MUM). Moreover, there was significant up
regulation of CYP3A4 expression via PXR activation for TBB and TBPH and their
metabolites. Induction of CYP3A4 might cause undesired drug-drug interactions,
lower bioavailability of pharmaceutical drugs, higher formation of reactive toxic
metabolites, or enhanced elimination of endogenous hormones, such as T3/T4, to
lead to endocrine disruption. These data provide new and important insights into
the toxicity of these new polybrominated flame retardants, TBB and TBPH, and
their metabolites.
PMID- 27506420
TI - Diabetes induction by total pancreatectomy in minipigs with simultaneous
splenectomy: a feasible approach for advanced diabetes research.
AB - BACKGROUND: Safe and reliable diabetes models are a key prerequisite for advanced
preclinical studies on diabetes. Chemical induction is the standard model of
diabetes in rodents and also widely used in large animal models of non-human
primates and minipigs. However, uncertain efficacy, the potential of beta-cell
regeneration, and relevant side effects are debatable aspects particularly in
large animals. Therefore, we aimed to evaluate a surgical approach of total
pancreatectomy combined with splenectomy for diabetes induction in an exploratory
study in Goettingen minipigs. METHODS: Total pancreatectomy was performed in
Goettingen minipigs (n = 4) under general anesthesia and endotracheal intubation.
Prior to surgery, a central venous line was established for drug application and
blood sampling. After median laparotomy, splenectomy was performed and the
lobular pancreas was carefully dissected with particular attention to the
duodenal vascular arcade. Close monitoring of blood glucose was initiated
immediately after surgery by standard glucometer measurement or continuous
glucose monitoring systems (CGMS). Exogenous insulin was given by multiple daily
subcutaneous (s.c.) injections or via insulin pump systems (CSII). Complete
endogenous insulin deficiency was confirmed by intravenous glucose tolerance test
(ivGTT) and measurement of c-peptide. For establishing a suitable regimen for
diabetes management, the animals were followed for 4-6 weeks. RESULTS: Following
pancreatectomy and splenectomy, the animals showed a quick recovery from surgery
and initial analgetic medication and volume substitution could be terminated
within 24 h. A rapid increase in blood glucose was observed immediately following
pancreatectomy necessitating insulin therapy. The induced exocrine insufficiency
did not cause any clinical symptoms. Complete insulin deficiency could be
confirmed in all animals by determination of negative c-peptide during glucose
challenge. The two regimen of insulin treatment (multiple daily injections (MDI)
and continuous subcutaneous insulin infusion (CSII)) were both feasible with
respect to acceptable glycemic control whereas CSII was considerably advantageous
in comfort and popularity for both animals and care takers. CONCLUSIONS: Surgical
pancreatectomy in combination with splenectomy to facilitate access to the
pancreas is a feasible model for efficient diabetes induction in minipigs. The
procedure itself and postoperative animal care could be performed without
complications in this exploratory study. Nevertheless, this approach requires
well-equipped infrastructure, experienced and skilled surgeons and
anesthesiologists and dedicated animal care takers. The impact of total
pancreatectomy in combination with splenectomy on the digestive and immune system
must be considered in the design and definition of end points of experimental
diabetes and transplantation studies.
PMID- 27506422
TI - Microbial Biotechnology 2020; microbiology of fossil fuel resources.
AB - This roadmap examines the future of microbiology research and technology in
fossil fuel energy recovery. Globally, the human population will be reliant on
fossil fuels for energy and chemical feedstocks for at least the medium term.
Microbiology is already important in many areas relevant to both upstream and
downstream activities in the oil industry. However, the discipline has struggled
for recognition in a world dominated by geophysicists and engineers despite
widely known but still poorly understood microbially mediated processes e.g.
reservoir biodegradation, reservoir souring and control, microbial enhanced oil
recovery. The role of microbiology is even less understood in developing
industries such as shale gas recovery by fracking or carbon capture by geological
storage. In the future, innovative biotechnologies may offer new routes to
reduced emissions pathways especially when applied to the vast unconventional
heavy oil resources formed, paradoxically, from microbial activities in the
geological past. However, despite this potential, recent low oil prices may make
industry funding hard to come by and recruitment of microbiologists by the oil
and gas industry may not be a high priority. With regards to public funded
research and the imperative for cheap secure energy for economic growth in a
growing world population, there are signs of inherent conflicts between policies
aimed at a low carbon future using renewable technologies and policies which
encourage technologies which maximize recovery from our conventional and
unconventional fossil fuel assets.
PMID- 27506421
TI - The differential impact of natural killer (NK) cell education via KIR2DL3 and
KIR3DL1 on CCL4 secretion in the context of in-vitro HIV infection.
AB - Carriage of certain inhibitory natural killer (NK) cell receptor (iNKR)/HLA
ligand pairs is associated with protection from infection and slow time to AIDS
implicating NK cells in HIV control. NK cells acquire functional potential
through education, which requires the engagement of iNKRs by their human
leucocyte antigen (HLA) ligands. HIV infection down-regulates cell surface HLA
A/B, but not HLA-C/E. We investigated how NK cell populations expressing
combinations of the iNKRs NKG2A, KIR2DL3 (2DL3) and KIR3DL1 (3DL1) responded to
autologous HIV infected CD4 (iCD4) cells. Purified NK cells from HIV-uninfected
individuals were stimulated with autologous HIV iCD4 or uninfected CD4 T cells.
Using flow cytometry we gated on each of the 8 NKG2A+/- 2DL3+/- 3DL1+/-
populations and analysed all possible combinations of interferon (IFN)-gamma,
CCL4 and CD107a functional subsets responding to iCD4 cells. Infected CD4 cells
induced differential frequencies of NKG2A+/- 2DL3+/- 3DL1+/- populations with
total IFN-gamma+ , CCL4+ and CD107a+ functional profiles. 2DL3+ NKG2A+ NK cells
had a higher frequency of responses to iCD4 than other populations studied. A
higher frequency of 2DL3+ NK cells responded to iCD4 from individuals that were
not HLA-C1 homozygotes. These results show that 2DL3+ NK cells are mediators of
HIV-specific responses. Furthermore, responses of NK cell populations to iCD4 are
influenced not only by NK cell education through specific KIR/HLA pairs, but also
by differential HIV-mediated changes in HLA expression.
PMID- 27506424
TI - A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific
Immediate Release Tablets.
AB - PURPOSE: The fabrication of ready-to-use immediate release tablets via 3D
printing provides a powerful tool to on-demand individualization of dosage form.
This work aims to adapt a widely used pharmaceutical grade polymer,
polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release
tablets via FDM 3D printing. METHODS: Dipyridamole or theophylline loaded
filaments were produced via processing a physical mixture of API (10%) and PVP in
the presence of plasticizer through hot-melt extrusion (HME). Computer software
was utilized to design a caplet-shaped tablet. The surface morphology of the
printed tablet was assessed using scanning electron microscopy (SEM). The
physical form of the drugs and its integrity following an FDM 3D printing were
assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In
vitro drug release studies for all 3D printed tablets were conducted in a USP II
dissolution apparatus. RESULTS: Bridging 3D printing process with HME in the
presence of a thermostable filler, talc, enabled the fabrication of immediate
release tablets at temperatures as low as 110 degrees C. The integrity of two
model drugs was maintained following HME and FDM 3D printing. XRPD indicated that
a portion of the loaded theophylline remained crystalline in the tablet. The
fabricated tablets demonstrated excellent mechanical properties, acceptable in
batch variability and an immediate in vitro release pattern. CONCLUSIONS:
Combining the advantages of PVP as an impeding polymer with FDM 3D printing at
low temperatures, this approach holds a potential in expanding the spectrum of
drugs that could be used in FDM 3D printing for on demand manufacturing of
individualised dosage forms.
PMID- 27506425
TI - Genetic Studies in Autism: Correspondence.
PMID- 27506426
TI - Do sudden onsets need to be perceived as new objects to capture attention? The
interplay between sensory transients and display configuration.
AB - Yantis and Jonides (1984) and Jonides and Yantis (1988) reported robust
involuntary attentional capture by sudden-onsets, the origin of which has been
debated. Prominent accounts have highlighted aspects that include the "new
object" status of a sudden-onset (Yantis & Hillstrom, 1994) and the substantial
luminance changes accompanying their appearance (Gellatly, Cole & Blurton, 1999;
Franconeri, Hollingworth & Simons, 2005), including relative differences in the
amount of sensory change between target and nontarget items (Pinto, Olivers &
Theeuwes, 2008). In this research we dissociate the amount of sensory change
accompanying sudden onsets from the extent to which they appear as newly created
objects in search displays. We attempted to determine the relative contribution
of local sensory changes and display configuration to attentional capture by
sudden-onsets. We showed that the display configuration of old objects modulates
the impact of capture caused by sudden-onsets.
PMID- 27506427
TI - The ticking time bomb: Using eye-tracking methodology to capture attentional
processing during gradual time constraints.
AB - Many decisions are made under suboptimal circumstances, such as time constraints.
We examined how different experiences of time constraints affected decision
strategies on a probabilistic inference task and whether individual differences
in working memory accounted for complex strategy use across different levels of
time. To examine information search and attentional processing, we used an
interactive eye-tracking paradigm where task information was occluded and only
revealed by an eye fixation to a given cell. Our results indicate that although
participants change search strategies during the most restricted times, the
occurrence of the shift in strategies depends both on how the constraints are
applied as well as individual differences in working memory. This suggests that,
in situations that require making decisions under time constraints, one can
influence performance by being sensitive to working memory and, potentially, by
acclimating people to the task time gradually.
PMID- 27506428
TI - Target object moderation of attentional orienting by gazes or arrows.
AB - Recent studies have attempted to demonstrate the importance of the
characteristics of directional cues and observers' traits in attentional
orienting. This study investigated how attentional orienting is influenced by
target processing. Two experiments showed the critical role played by target
processing in attentional orienting that relies on eye-gaze and arrow cues. In
Experiment 1, stronger attentional orienting was observed under the object-target
condition compared with the scrambled-display condition, irrespective of whether
gaze or arrow cues were used. The results indicated that meaningful targets
produced stronger attentional orienting than did meaningless targets, regardless
of the social characteristics of the target. Experiment 2, which investigated
whether attentional orienting was influenced by differences in the meaningfulness
of targets regardless of their perceptual features, used participants' own faces
and the faces of others as target stimuli; one's own face is typically more
meaningful than the face of another. The results showed stronger attentional
orienting in response to one's own face than in response to another's face under
both gaze and arrow conditions. These findings suggest that the use of task
irrelevant meaningful information as targets may be effective in enhancing
attention, regardless of perceptual features.
PMID- 27506429
TI - Measurement of global DNA methylation levels by flow cytometry in mouse
fibroblasts.
AB - DNA Methylation, 5meC, is an epigenetic modification that acts as an important
regulator of genomic stability and gene expressivity. Genome-wide changes in
methylation have been associated with lineage-specific changes in gene expression
profiles during development and in some cell-based pathologies, including
oncogenesis. Cost-effective and rapid platforms for the detection of changes in
the global levels of methylation are of value for the investigation of the
processes that regulate methylation. Flow cytometry allows rapid and quantitative
analysis of epitopes within a large number of cells. We have recently optimised
the conditions required for valid detection of 5meC by immunofluorescence
microscopy. These studies showed that immunological detection of 5meC requires
the sequential denaturation of chromatin by a brief period of acidification
followed by a partial tryptic digestion step. We have assessed the reliability of
flow cytometry for the detection of changes in 5meC when coupled with this
optimised epitope retrieval strategy. This study provides support for the use of
high throughput screening of 5meC by flow cytometry for the analysis of the
epigenetic regulation of important cell transitions.
PMID- 27506430
TI - A Unified Approach for the Enantioselective Synthesis of the Brominated
Chamigrene Sesquiterpenes.
AB - The brominated chamigrene sesquiterpenes constitute a large subclass of
bromocyclohexane-containing natural products, yet no general enantioselective
strategy for the synthesis of these small molecules exists. Herein we report a
general strategy for accessing this family of secondary metabolites, including
the enantioselective synthesis of (-)-alpha- and (-)-ent-beta-bromochamigrene, (
)-dactylone, and (+)-aplydactone. Access to these molecules is enabled by a
stereospecific bromopolyene cyclization initiated by the solvolysis of an
enantiomerically enriched vicinal bromochloride.
PMID- 27506432
TI - Self-reported wellbeing and body image after abdominoperineal excision for rectal
cancer.
AB - PURPOSE: Patients with low rectal cancer are often operated with an
abdominoperineal excision (APE) rendering them a permanent stoma. The surgical
procedure itself, the cancer diagnosis, and the permanent stoma might all affect
quality of life. The aim of this study was to explore wellbeing and body image 3
years after APE in a population-based cohort of patients. METHODS: All patients
with rectal cancer operated with an APE between 2007 and 2009 were identified
using the Swedish ColoRectal Cancer Registry. A total of 545 patients answered a
questionnaire 3 years after surgery. Two open-ended questions were analyzed with
a mixed method design using both qualitative and quantitative content analysis.
Main themes and sub-themes on wellbeing and body image were identified. RESULTS:
Three main themes were identified: bodily limitations, mental suffering, and
acceptance. Bodily limitations included other symptoms than stoma-related
problems. A majority of patients expressed acceptance to their situation
regardless of bodily limitations and mental suffering. However, 18 % did not
describe any acceptance of their current situation. CONCLUSIONS: Most patients
expressed acceptance reflecting wellbeing 3 years after APE for rectal cancer.
There is, however, a subset of patients (18 %) who describe bodily limitations
and mental suffering without acceptance and who require further support. Many
aspects of the portrayed bodily limitations and mental suffering could be
prevented or treated. TRIAL REGISTRATION: NCT01296984.
PMID- 27506431
TI - 177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer:
safety, efficacy, and quality of life assessment.
AB - PURPOSE: The purpose of this study was to evaluate the efficacy and safety of a
novel theranostic agent, 177Lu-DKFZ-PSMA-617 therapy in metastatic castration
resistant prostate cancer (mCRPC). METHODS: Thirty-one mCRPC patients with
progressive disease despite second-line hormonal therapy and/or docetaxel
chemotherapy were recruited for the study. All patients underwent diagnostic68Ga
PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then
underwent quarterly 177Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function,
liver function tests, and serum PSA levels were recorded before and after therapy
at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed
with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1
criteria. Clinical response was assessed by visual analogue score (VASmax)
analgesic score (AS), Karanofsky performance status (KPS), and ttoxicity and
response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria.
RESULTS: The mean age of patients was 65.93 +/- 9.77 years (range: 38-81 years).
The mean activity administered in the 31 patients was 5069 +/- 1845 MBq ranging
from one to four cycles. There was a decline in the mean serum PSA levels from
the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based
on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete
response (CR), partial response(PR), stable disease (SD), and progressive disease
(PD), respectively. Metabolic response revealed 2/6 patients with CR, and the
remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score
decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after
therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The
mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two
patients experienced grade I and grade II hemoglobin toxicity each. None of the
patients experienced nephrotoxicity or hepatotoxicity. CONCLUSION: 177Lu-DKFZ
PSMA-617 radionuclide therapy is a safe and effective approach in the treatment
of mCRPC patients.
PMID- 27506434
TI - Erratum to: Picosecond pulsed infrared laser tuned to amide I band dissociates
polyglutamine fibrils in cells.
PMID- 27506433
TI - Clinical and surgical factors associated with organ/space surgical site infection
after laparoscopic gastrectomy for gastric cancer.
AB - BACKGROUND: Surgical site infection (SSI), particularly organ/space SSI, remains
a clinically important issue even after laparoscopic gastrectomy (LG) for gastric
cancer (GC). This study aimed to identify specific clinical and surgical factors
associated with organ/space SSI after LG. METHODS: This was a retrospective study
of 407 patients who underwent LG for clinical stage I GC. SSI was defined
according to the National Nosocomial Infection Surveillance System. The incidence
and treatment outcomes of either incisional or organ/space SSI after LG were
examined, and the risk factors for each type of SSI were identified using
univariate and multivariate analyses. RESULTS: Organ/space SSI was observed in 21
patients (5.2 %), while incisional SSI was detected in 18 patients (4.4 %).
Although no mortality was observed, the occurrence of either incisional or
organ/space SSI significantly prolonged postoperative hospital stays (p = 0.000
and 0.000, respectively); however, organ/space SSI required more re-operations
and re-admissions, and eventually longer total hospital stays than incisional SSI
(p = 0.036). Intra-abdominal abscess around the pancreas was the main cause of
organ/space SSI, while no anastomotic leakage was observed. Multivariate analyses
identified male gender (odds ratio (OR) 3.385; 95 % confidence interval (CI)
1.073-15.07, p = 0.037), chronic liver disease (OR 8.897; 95 % CI 2.502-28.99, p
= 0.001), and total gastrectomy (TG) (OR 3.817; 95 % CI 1.380-10.24, p = 0.011)
as independent risk factors for organ/space SSI, while TG (OR 3.130; 95 % CI
1.102-8.768, p = 0.033) and operation time >=320 min (OR 3.732; 95 % CI 1.109
16.98, p = 0.033) were independently associated with incisional SSI. CONCLUSIONS:
Male gender, chronic liver disease, and TG are independent risk factors for
organ/space SSI after LG for GC; thus, meticulous surgical procedures need to be
performed among patients with these specific risk factors.
PMID- 27506435
TI - [Rank of outcome parameters in the treatment of depression : Results of a Delphi
panel survey].
AB - BACKGROUND: In the context of new drug benefit assessments a list of outcome
parameter are evaluated. Currently it is unclear, how different outcome
parameters are weighed in the overall assessment. OBJECTIVES: The objective of
the survey is to rank relevant outcome parameters in the treatment of depression,
which may be considered in benefit the assessment of new antidepressants.
MATERIALS AND METHODS: In 2015 a Delphi panel survey with 30 general
practitioners and specialists in Germany was performed regarding the benefit
assessment of antidepressants. On the basis of two fictive casuistics (patients
with depressive disorders) the physicians weighed a range of relevant outcome
parameters regarding efficacy, quality of life, safety and tolerability according
to their relevance to clinical practice. RESULTS: Regarding efficacy, response,
remission and recovery were rated as the most important outcomes. Regarding
quality of life, handling of the daily household activities and mental
performance were rated as most important. Suicidality was rated as the most
important outcome regarding safety and tolerability. CONCLUSIONS: Individual
outcome parameters were rated differently by the physicians regarding their
relevance to clinical practice. The results indicate that outcome parameters
should be weighed differently when assessing the overall benefit of new
antidepressants.
PMID- 27506436
TI - Managing player load in professional rugby union: a review of current knowledge
and practices.
AB - BACKGROUND: The loads to which professional rugby players are subjected has been
identified as a concern by coaches, players and administrators. In November 2014,
World Rugby commissioned an expert group to identify the physical demands and non
physical load issues associated with participation in professional rugby.
OBJECTIVE: To describe the current state of knowledge about the loads encountered
by professional rugby players and the implications for their physical and mental
health. FINDINGS: The group defined 'load' as it relates to professional rugby
players as the total stressors and demands applied to the players. In the 2013
2014 seasons, 40% of professional players appeared in 20 matches or more, and 5%
of players appeared in 30 matches or more. Matches account for ~5-11% of exposure
to rugby-related activities (matches, team and individual training sessions)
during professional competitions. The match injury rate is about 27 times higher
than that in training. The working group surmised that players entering a new
level of play, players with unresolved previous injuries, players who are
relatively older and players who are subjected to rapid increases in load are
probably at increased risk of injury. A mix of 'objective' and 'subjective'
measures in conjunction with effective communication among team staff and between
staff and players was held to be the best approach to monitoring and managing
player loads. While comprehensive monitoring holds promise for individually
addressing player loads, it brings with it ethical and legal responsibilities
that rugby organisations need to address to ensure that players' personal
information is adequately protected. CONCLUSIONS: Administrators, broadcasters,
team owners, team staff and the players themselves have important roles in
balancing the desire to have the 'best players' on the field with the ongoing
health of players. In contrast, the coaching, fitness and medical staff exert
significant control over the activities, duration and intensity of training
sessions. If load is a major risk factor for injury, then managing training loads
should be an important element in enabling players to perform in a fit state as
often as possible.
PMID- 27506437
TI - Measuring water fluxes in forests: the need for integrative platforms of
analysis.
PMID- 27506438
TI - Simple and Sensitive Quantification of Ghrelin Hormone in Human Plasma Using SBSE
HPLC/DAD-MS.
AB - During a decade and more since its discovery, the emerging physiological roles of
ghrelin in mammalian are increasingly being introduced, proposing a critical need
for its quantification in biological milieu. Here in, a simple and sensitive
single-step method for extraction and quantification of ghrelin in human plasma
was developed and validated using stir bar sorptive extraction (SBSE) followed by
high-performance liquid chromatography (HPLC) with diode array detection (DAD)
coupled to mass spectrometry (MS). Influential parameters of SBSE procedure were
optimized including extraction and desorption times of 45 and 30 min,
respectively; pH of 4; no addition of salt. The sum of peak heights of three most
intense selected ions in mass spectrum (844, 1125 and 1686 m/z) related to 4-, 3-
and 2-fold-charged ions of ghrelin was used for quantification. Validation
parameters containing linear dynamic range, limit of quantification and limit of
detection were 0.02-80, 0.02 and 0.007 ug L-1, respectively, and calculated
relative standard deviation for peak heights was 6.5% (0.7 ug L-1 standard
solution). Mean recovery for ghrelin in spiked plasma samples was 96% +/- 3. The
efficiency of the SBSE-HPLC/DAD-MS procedure was proved by analysis of plasma
samples from obese patients undergoing gastric plication surgery. The suggested
methodology would contribute to simple and fast analysis of ghrelin levels in
obesity and related diseases and also biochemical cycles in which gherlin is
present.
PMID- 27506439
TI - Sphingomonas naphthae sp. nov., isolated from oil-contaminated soil.
AB - During the study of hydrocarbon-degrading bacteria in the oil-contaminated soil
of Gunsan, North Jeolla Province, South Korea, a yellow, Gram-stain-negative,
aerobic, motile, rod-shaped bacterium, designated strain DKC-5-1T, was isolated.
This strain was non-sporulating, catalase-negative and oxidase-positive. It was
able to grow at 10-33 degrees C, pH 6.0-8.5 and at an NaCl concentration of 0
1.5 % (w/v). This strain was characterized taxonomically using a polyphasic
approach. Based on 16S rRNA gene sequence analysis, strain DKC-5-1T belongs to
the genus Sphingomonas and is closely related to Sphingomonas laterariae LNB2T
(96.65 % sequence similarity), Sphingomonas haloaromaticamans A175T (96.63 %
sequence similarity), Sphingomonas histidinilytica UM2T (96.63 % sequence
similarity), and Sphingomonas wittichii RW1T (96.43 % sequence similarity). The
only respiratory quinone was ubiquinone-10 and the major polyamine was
homospermidine. The polar lipid profile revealed the presence of
phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine,
phosphatidylcholine, sphingoglycolipid and phosphatidyldimethylethanolamine. The
predominant fatty acids of strain DKC-5-1T were summed feature 8 (C18 : 1omega7c
and/or C18 : 1omega6c), C16 : 0, C14 : 0 2-OH, summed feature 3 (C16 : 1omega7c
and/or C16 : 1omega6c), C17 : 1omega6c and C14 : 0. The genomic DNA G+C content
of this novel strain was 65.9 mol%. Morphological, physiological, chemotaxonomic
and phylogenetic analyses clearly distinguished this strain from its closest
phylogenetic neighbours. Thus, strain DKC-5-1T represents a novel species of the
genus Sphingomonas, for which the name Sphingomonasnaphthae sp. nov. is proposed.
The type strain is DKC-5-1T (=KEMB 9005-380T=KACC 18716T=JCM 31294T).
PMID- 27506440
TI - Experiences of Japanese aged care: the pursuit of optimal health and cultural
engagement.
AB - Japan is a super-ageing society that faces pressures on its aged care system from
a growing population of older adults. Naturalistic observations were undertaken
at eight aged care facilities in central and northern Japan to explore how aged
care is configured. Four aspects of contemporary provision were identified that
offer potential gains in quality of life and health. The Japanese government
mandates that aged care facilities must employ a qualified nutritionist to
oversee meal preparation, fostering optimal dietary intake. A concept of life
rehabilitation seeks to maximise physical and cognitive performance, with
possible longevity gains. Low staff to resident ratios are also mandated by the
Japanese government to afford residents high levels of interpersonal care.
Finally, Japanese facilities prioritise experiences of seasonality and culture,
connecting frail older people to the world beyond their walls.
PMID- 27506442
TI - Attitudes of Primary Care Physicians Toward Sickle Cell Disease Care, Guidelines,
and Comanaging Hydroxyurea With a Specialist.
AB - BACKGROUND: Sickle cell disease (SCD) is a complex chronic disease requiring
multidisciplinary care that involves primary care physicians (PCPs) working with
a hematologist or SCD specialists. However, PCPs often lack access to SCD
specialists and are unaware of SCD guidelines or efficacious treatment. METHODS:
We partnered with Community Care of North Carolina (CCNC) to identify assigned
PCPs for SCD patients with Medicaid across North Carolina. CCNC network
administrators distributed a web-based questionnaire for completion. The
questionnaire involved 12 self-reported items on a yes-no or a 1 to 5 Likert-type
scale that assessed PCP attitudes toward SCD care, awareness of recent
guidelines, and comanaging hydroxyurea. RESULTS: Of the 53 PCPs who completed the
electronic survey, 73% felt they were comfortable with the number of SCD patients
in their practice. Most PCPs reported having infrequent communications with an
SCD specialist (67%) and most were also not aware of the 2014 SCD guidelines
(66%). Many reported that they would frequently use the new SCD guidelines if
provided to them (76%). Furthermore, 51% of PCPs expressed comfort with using
mobile apps to access SCD guidelines and provided email contact to receive
further information. The majority also reported being comfortable comanaging
hydroxyurea with an SCD specialist (65%). CONCLUSION: Few PCPs in North Carolina
were aware of the new SCD guidelines or had regular communication with an SCD
specialist. The majority of PCPs, however, demonstrated a favorable attitude
toward receiving the SCD guidelines and comanaging hydroxyurea with a specialist.
In response to this gap in care, we have developed a mobile-based SCD toolbox
specifically for PCPs to provide guidelines, algorithms, and a method to
communicate with local SCD specialists. With the interest in receiving these
guidelines, we are confident the toolbox will provide an easy to use platform to
assist PCPs to utilize the SCD guidelines.
PMID- 27506443
TI - Reaching Urban Poor Hypertensive Patients: A Novel Model of Chronic Disease Care
Versus a Traditional Fee-for-Service Approach.
AB - BACKGROUND: There is a significant disparity in hypertensive treatment rates
between those with and without health insurance. If left untreated, hypertension
leads to significant morbidity and mortality. The uninsured face numerous
barriers to access chronic disease care. We developed the Community-based Chronic
Disease Management (CCDM) clinics specifically for the uninsured with
hypertension utilizing nurse-led teams, community-based locations, and evidence
based clinical protocols. All services, including laboratory and medications, are
provided on-site and free of charge. METHODS: In order to ascertain if the CCDM
model of care was as effective as traditional models of care in achieving blood
pressure goals, we compared CCDM clinics' hypertensive care outcomes with 2
traditional fee-for-service physician-led clinics. All the clinics are located
near one another in poor urban neighborhoods of Milwaukee, Wisconsin. RESULTS:
Patients seen at the CCDM clinics and at 1 of the 2 traditional clinics showed a
statistically significant improvement in reaching blood pressure goal at 6 months
( P < .001 and P < .05, respectively). Logistic regression analysis found no
difference in attaining blood pressure goal at 6 months for either of the 2 fee
for-service clinics when compared with the CCDM clinics. CONCLUSION: The CCDM
model of care is at least as effective in controlling hypertension as more
traditional fee-for-service models caring for the same population. The CCDM model
of care to treat hypertension may offer another approach for engaging the urban
poor in chronic disease care.
PMID- 27506444
TI - Publicly funded postpartum contraception use is associated with a reduction in
the rate of subsequent preterm birth.
PMID- 27506445
TI - Ultrasound-based IOTA simple rules allow accurate malignancy risk estimation for
adnexal masses.
PMID- 27506446
TI - Effects of addition of Aspergillus oryzae culture and 2-hydroxyl-4-(methylthio)
butanoic acid on milk performance and rumen fermentation of dairy cows.
AB - To investigate effects of Aspergillus oryzae culture (AOC) and 2-hydroxy-4
(methylthio) butanoic acid (HMB) on milk performance and rumen fermentation of
dairy cows. Sixty-four multiparous Chinese Holstein cows were randomly allocated
into four experimental diets: (i) Control diet; (ii) AOC diet: 5 g AOC/day per
head; (iii) HMB diet: 25 g HMB/day; and (iv) AH diet: 5 g AOC plus 25 g HMB/day.
Added HMB tended to increase the yield of milk protein (P = 0.06) and 3.5% fat
corrected milk (P = 0.08) and milk fat content (P = 0.09). Milk fat yield (P =
0.03) and the contents of milk protein (P = 0.05) were increased by adding HMB.
The cows fed on AOC diet had a tendency for higher body weight (BW) gain (P =
0.08). Addition of AOC, HMB and AH increased content of microbial protein (MCP)
and total volatile fatty acids (VFA) (P < 0.01) in rumen fluid. Populations of
rumen fungi, Fibrobacter succinogenes and Ruminococcus flavefaciens relative to
total bacterial 16S rDNA (P <= 0.03) and activity of carboxymethylcellulase
(CMCase) (P < 0.01) were increased with added AOC or HMB. It is inferred that
added AOC or HMB can increase the contents of MCP and total VFA potentially by
stimulating rumen microbe populations and CMCase activity.
PMID- 27506448
TI - Sexual Assault: What Every Emergency Provider Needs to Know.
PMID- 27506447
TI - Transcriptional regulation of the proto-oncogene Zfp521 by SPI1 (PU.1) and
HOXC13.
AB - The mouse zinc-finger gene Zfp521 (also known as ecotropic viral insertion site
3; Evi3; and ZNF521 in humans) has been identified as a B-cell proto-oncogene,
causing leukemia in mice following retroviral insertions in its promoter region
that drive Zfp521 over-expression. Furthermore, ZNF521 is expressed in human
hematopoietic cells, and translocations between ZNF521 and PAX5 are associated
with pediatric acute lymphoblastic leukemia. However, the regulatory factors that
control Zfp521 expression directly have not been characterized. Here we
demonstrate that the transcription factors SPI1 (PU.1) and HOXC13 synergistically
regulate Zfp521 expression, and identify the regions of the Zfp521 promoter
required for this transcriptional activity. We also show that SPI1 and HOXC13
activate Zfp521 in a dose-dependent manner. Our data support a role for this
regulatory mechanism in vivo, as transgenic mice over-expressing Hoxc13 in the
fetal liver show a strong correlation between Hoxc13 expression levels and Zfp521
expression. Overall these experiments provide insights into the regulation of
Zfp521 expression in a nononcogenic context. The identification of transcription
factors capable of activating Zfp521 provides a foundation for further
investigation of the regulatory mechanisms involved in ZFP521-driven cell
differentiation processes and diseases linked to Zfp521 mis-expression.
PMID- 27506449
TI - Dual Therapeutic Action of a Neutralizing Anti-FGF2 Aptamer in Bone Disease and
Bone Cancer Pain.
AB - Fibroblast growth factor 2 (FGF2) plays a crucial role in bone remodeling and
disease progression. However, the potential of FGF2 antagonists for treatment of
patients with bone diseases has not yet been explored. Therefore, we generated a
novel RNA aptamer, APT-F2, specific for human FGF2 and characterized its
properties in vitro and in vivo. APT-F2 blocked binding of FGF2 to each of its
four cellular receptors, inhibited FGF2-induced downstream signaling and cells
proliferation, and restored osteoblast differentiation blocked by FGF2. APT-F2P,
a PEGylated form of APT-F2, effectively blocked the bone disruption in mouse and
rat models of arthritis and osteoporosis. Treatment with APT-F2P also exerted a
strong analgesic effect, equivalent to morphine, in a mouse model of bone cancer
pain. These findings demonstrated dual therapeutic action of APT-F2P in bone
diseases and pain, providing a promising approach to the treatment of bone
diseases.
PMID- 27506450
TI - Type I Interferons Interfere with the Capacity of mRNA Lipoplex Vaccines to
Elicit Cytolytic T Cell Responses.
AB - Given their high potential to evoke cytolytic T cell responses, tumor antigen
encoding messenger RNA (mRNA) vaccines are now being intensively explored as
therapeutic cancer vaccines. mRNA vaccines clearly benefit from wrapping the mRNA
into nano-sized carriers such as lipoplexes that protect the mRNA from
degradation and increase its uptake by dendritic cells in vivo. Nevertheless, the
early innate host factors that regulate the induction of cytolytic T cells to
mRNA lipoplex vaccines have remained unresolved. Here, we demonstrate that mRNA
lipoplexes induce a potent type I interferon (IFN) response upon subcutaneous,
intradermal and intranodal injection. Regardless of the route of immunization
applied, these type I IFNs interfered with the generation of potent cytolytic T
cell responses. Most importantly, blocking type I IFN signaling at the site of
immunization through the use of an IFNAR blocking antibody greatly enhanced the
prophylactic and therapeutic antitumor efficacy of mRNA lipoplexes in the highly
aggressive B16 melanoma model. As type I IFN induction appears to be inherent to
the mRNA itself rather than to unique properties of the mRNA lipoplex
formulation, preventing type I IFN induction and/or IFNAR signaling at the site
of immunization might constitute a widely applicable strategy to improve the
potency of mRNA vaccination.
PMID- 27506451
TI - Therapeutic Potential of Immunoproteasome Inhibition in Duchenne Muscular
Dystrophy.
AB - Duchenne muscular dystrophy is an inherited fatal genetic disease characterized
by mutations in dystrophin gene, causing membrane fragility leading to myofiber
necrosis and inflammatory cell recruitment in dystrophic muscles. The resulting
environment enriched in proinflammatory cytokines, like IFN-gamma and TNF-alpha,
determines the transformation of myofiber constitutive proteasome into the
immunoproteasome, a multisubunit complex involved in the activation of cell
mediate immunity. This event has a fundamental role in producing peptides for
antigen presentation by MHC class I, for the immune response and also for
cytokine production and T-cell differentiation. Here, we characterized for the
first time the presence of T-lymphocytes activated against revertant dystrophin
epitopes, in the animal model of Duchenne muscular dystrophy, the mdx mice.
Moreover, we specifically blocked i-proteasome subunit LMP7, which was up
regulated in dystrophic skeletal muscles, and we demonstrated the rescue of the
dystrophin expression and the amelioration of the dystrophic phenotype. The i
proteasome blocking lowered myofiber MHC class I expression and self-antigen
presentation to T cells, thus reducing the specific antidystrophin T cell
response, the muscular cell infiltrate, and proinflammatory cytokine production,
together with muscle force recovery. We suggest that i-proteasome inhibition
should be considered as new promising therapeutic approach for Duchenne muscular
dystrophy pathology.
PMID- 27506452
TI - Adaptive Immune Response Impairs the Efficacy of Autologous Transplantation of
Engineered Stem Cells in Dystrophic Dogs.
AB - Duchenne muscular dystrophy is the most common genetic muscular dystrophy. It is
caused by mutations in the dystrophin gene, leading to absence of muscular
dystrophin and to progressive degeneration of skeletal muscle. We have
demonstrated that the exon skipping method safely and efficiently brings to the
expression of a functional dystrophin in dystrophic CD133+ cells injected
scid/mdx mice. Golden Retriever muscular dystrophic (GRMD) dogs represent the
best preclinical model of Duchenne muscular dystrophy, mimicking the human
pathology in genotypic and phenotypic aspects. Here, we assess the capacity of
intra-arterial delivered autologous engineered canine CD133+ cells of restoring
dystrophin expression in Golden Retriever muscular dystrophy. This is the first
demonstration of five-year follow up study, showing initial clinical amelioration
followed by stabilization in mild and severe affected Golden Retriever muscular
dystrophy dogs. The occurrence of T-cell response in three Golden Retriever
muscular dystrophy dogs, consistent with a memory response boosted by the exon
skipped-dystrophin protein, suggests an adaptive immune response against
dystrophin.
PMID- 27506454
TI - Conidiobolus macrosporus (Entomophthorales), a mosquito pathogen in Central
Brazil.
AB - A new fungal pathogen of Culicinae (Diptera: Culicidae) adults, Conidiobolus
macrosporus (Entomophthorales: Ancylistaceae), was detected and isolated during a
survey of mosquito pathogens close to the city of Aruana, Goias State, in
December 2014. The morphological characteristics of C. macrosporus are presented,
and reasons for some uncertainty about this identification are discussed. The
pathogenicity and high virulence of this fungus for Aedes aegypti were confirmed
in laboratory conditions. Mortality of adults exposed to conidia was observed
within 24h of exposure to the pathogen, and increased to 100% as quickly as 3days
after inoculation (with the highest conidial concentration tested,
8.3*10(4)conidia/cm(2)). Repeated attempts to obtain genomic sequence data failed
despite confirmations that the DNA extraction methods were themselves successful.
PMID- 27506453
TI - Enriched retinal ganglion cells derived from human embryonic stem cells.
AB - Optic neuropathies are characterised by a loss of retinal ganglion cells (RGCs)
that lead to vision impairment. Development of cell therapy requires a better
understanding of the signals that direct stem cells into RGCs. Human embryonic
stem cells (hESCs) represent an unlimited cellular source for generation of human
RGCs in vitro. In this study, we present a 45-day protocol that utilises magnetic
activated cell sorting to generate enriched population of RGCs via stepwise
retinal differentiation using hESCs. We performed an extensive characterization
of these stem cell-derived RGCs by examining the gene and protein expressions of
a panel of neural/RGC markers. Furthermore, whole transcriptome analysis
demonstrated similarity of the hESC-derived RGCs to human adult RGCs. The
enriched hESC-RGCs possess long axons, functional electrophysiological profiles
and axonal transport of mitochondria, suggestive of maturity. In summary, this
RGC differentiation protocol can generate an enriched population of functional
RGCs from hESCs, allowing future studies on disease modeling of optic
neuropathies and development of cell therapies.
PMID- 27506455
TI - Substitution of outpatient care with primary care: a feasibility study on the
experiences among general practitioners, medical specialists and patients.
AB - BACKGROUND: Reinforcing the gatekeeping role of general practitioners (GPs) by
embedding specialist knowledge into primary care is seen as a possibility for
stimulating a more sustainable healthcare system and avoiding unnecessary
referrals to outpatient care. An intervention called Primary Care Plus (PC+) was
developed to achieve these goals. The objective of this study is to gain insight
into: (1) the content and added value of PC+ consultations according to
stakeholders, and (2) patient satisfaction with PC+ compared to outpatient care.
METHODS: A feasibility study was conducted in the southern part of the
Netherlands between April 2013 and January 2014. Data was collected using GP,
medical specialist and patient questionnaires. Patient characteristics and
medical specialty data were collected through the data system of a GP referral
department. RESULTS: GPs indicated that they would have referred 85.4 % of their
PC+ patients to outpatient care in the hypothetical case that PC+ was not
available. Medical specialists indicated that about one fifth of the patients
needed follow-up in outpatient care and 75.9 % of the consultations were of added
value to patient care. The patient satisfaction results appear to be in favour of
PC+. CONCLUSION: PC+ seems to be a feasible intervention to be implemented on a
larger scale, because it has the potential to prevent unnecessary hospital
referrals. PC+ will be evaluated on a larger scale regarding the effects on
health outcomes, quality of care and costs (Triple Aim principle).
PMID- 27506457
TI - Application of Mycobacterium Leprae-specific cellular and serological tests for
the differential diagnosis of leprosy from confounding dermatoses.
AB - Mycobacterium leprae-specific serological and cell-mediated-immunity/CMI test
were evaluated for the differential diagnosis of multibacillary/MB, and
paucibacillary/PB leprosy from other dermatoses. Whole-blood assay/WBA/IFNgamma
stimulated with LID-1 antigen and ELISA tests for IgG to LID-1 and IgM to PGL-I
were performed. WBA/LID-1/IFNgamma production was observed in 72% PB, 11% MB
leprosy, 38% dermatoses, 40% healthy endemic controls/EC. The receiver operating
curve/ROC for WBA/LID-1 in PB versus other dermatoses showed 72.5% sensitivity,
61.5% specificity and an area-under-the-curve/AUC=0.75; 74% positive predictive
value/PPV, 59% negative predictive value/NPV. Anti PGL-I serology was positive in
67% MB, 8% PB leprosy, 6% of other dermatoses; its sensitivity for MB=66%,
specificity=93%, AUC=0.89; PPV=91%, NPV=72%. Anti-LID-1 serology was positive in
87% MB, 7% PB leprosy, all other participants were seronegative; 87.5%
sensitivity for MB, 100% specificity, AUC=0.97; PPV=100%, NPV=88%. In highly
endemic areas anti-LID-1/PGL-I serology and WBA/LID-1-represent useful tools for
the differential diagnosis of leprosy from other confounding dermatoses.
PMID- 27506456
TI - Assessment of sedentary behaviors and transport-related activities by
questionnaire: a validation study.
AB - BACKGROUND: Comprehensive assessment of sedentary behavior (SB) and physical
activity (PA), including transport-related activities (TRA), is required to
design innovative PA promotion strategies. There are few validated instruments
that simultaneously assess the different components of human movement according
to their context of practice (e.g. work, transport, leisure). We examined test
retest reliability and validity of the Sedentary, Transportation and Activity
Questionnaire (STAQ), a newly developed questionnaire dedicated to assessing
context-specific SB, TRA and PA. METHODS: Ninety six subjects (51 women) kept a
contextualized activity-logbook and wore a hip accelerometer (Actigraph GT3X +
(TM)) for a 7-day or 14-day period, at the end of which they completed the STAQ.
Activity-energy expenditure was measured in a subgroup of 45 subjects using the
double labeled water (DLW) method. Test-retest reliability was assessed using
intra-class-coefficients (ICC) in a subgroup of 32 subjects who filled the
questionnaire twice one month apart. Accelerometry was annotated using the
logbook to obtain total and context-specific objective estimates of SB. Spearman
correlations, Bland-Altman plots and ICC were used to analyze validity with
logbook, accelerometry and DLW data validity criteria. RESULTS: Test-retest
reliability was fair for total sitting time (ICC = 0.52), good to excellent for
work sitting time (ICC = 0.71), transport-related walking (ICC = 0.61) and car
use (ICC = 0.67), and leisure screen-related SB (ICC = 0.64-0.79), but poor for
total sitting time during leisure and transport-related contexts. For validity,
compared to accelerometry, significant correlations were found for STAQ estimates
of total (r = 0.54) and context-specific sitting times with stronger correlations
for work sitting time (r = 0.88), and screen times (TV/DVD viewing: r = 0.46;
other screens: r = 0.42) than for transport (r = 0.35) or leisure-related sitting
times (r = 0.19). Compared to contextualized logbook, STAQ estimates of TRA was
higher for car (r = 0.65) than for active transport (r = 0.41). The questionnaire
generally overestimated work- and leisure-related SB and sitting times, while it
underestimated total and transport-related sitting times. CONCLUSIONS: The STAQ
showed acceptable reliability and a good ranking validity for assessment of
context-specific SB and TRA. This instrument appears as a useful tool to study
SB, TRA and PA in context in adults.
PMID- 27506458
TI - ZSM-5 with controllable acidity as an efficient catalyst for a highly adjustable
propene/ethene ratio in the 1-butene cracking.
AB - A facile strategy was proposed to realize the precise control of zeolitic acidity
by selective cracking of a silane with an acid site. Modified ZSM-5 with
controllable acidity brought about a highly adjustable propene/ethene (P/E) ratio
in the 1-butene cracking.
PMID- 27506459
TI - Different lines of evidence used to delimit species in ticks: A study of the
South American populations of Amblyomma parvum (Acari: Ixodidae).
AB - The goal of this work was to combine different lines of evidence besides that of
molecular markers to delimit species in ticks when the molecular data are not
totally congruent. Two groups (Argentina, Brazil) of South American populations
of Amblyomma parvum were compared to test whether the splitting of these two
lineages suggested by genetic analyses is complete. Comparative studies of
reproductive compatibility, morphological analyses of fixed characters, and
comparison of population distributions in spatially defined ecological niches
were performed.The morphological comparisons of both discrete and morphometric
characters showed no differences among A. parvum ticks from Argentina and Brazil.
The intercrosses and backcrosses showed evidence of pre- and post-zygotic
compatibility between the two groups. No significant differences in environmental
traits were found which would justify the separation of the records of A. parvum
in distinct groups. Although the gene flow between the two groups of populations
is limited, the absence of reproductive barriers, the lack of significant
morphological differences, and the absence of significant differences in the
niche preferences indicate that populations of A. parvum from Argentina and
Brazil should be treated as a single species. The speciation conjectures
suggested by some analyses of mitochondrial DNA sequences were not supported when
different lines of evidences were compared.
PMID- 27506460
TI - Role of sonography in the diagnosis and treatment of a ganglion cyst compressing
the lateral branch of deep peroneal nerve.
AB - Selective compression neuropathy of the lateral branch of the deep peroneal nerve
is rare. A 55-year-old woman with ankle instability and mild weakness of
extension of the toes was examined with sonography (US), which revealed the
presence of a ganglion cyst compressing selectively the lateral branch of the
deep peroneal nerve. US-guided aspiration of the cyst resulted in nerve
decompression and progressive resolution of symptoms. This case demonstrates the
importance of examining the deep peroneal nerve and its branches when performing
US in the clinical setting of ankle instability. (c) 2016 Wiley Periodicals, Inc.
J Clin Ultrasound 45:108-111, 2017.
PMID- 27506461
TI - Peer-instructed seminar attendance is associated with improved preparation,
deeper learning and higher exam scores: a survey study.
AB - BACKGROUND: Active engagement in education improves learning outcomes. To enhance
active participation in seminars, a student-centered course design was
implemented and evaluated in terms of self-reported preparation, student
motivation and exam scores. We hypothesized that small group learning with
intensive peer interaction, using buzz-groups followed by plenary discussion,
would motivate students to prepare seminar assignments at home and to actively
engage in the seminars. Active engagement involved discussion of the preparatory
assignments until consensus was reached. METHODS: In total seven seminars were
scheduled in a 10-week physiology course of an undergraduate Biomedical Sciences
program. After each seminar, students were asked to fill out their perceptions of
preparation and quality of the seminar (deepening of knowledge and confidence in
answers) on a five-point scale using electronic questionnaires. Student motives
were first collected using open questions. In the final questionnaire students
were asked to indicate on a five-point scale how each motive was perceived.
Students overall explanations why they had learned from seminars were collected
via open questions in the final questionnaire. One hundred and twenty-four
students of the cohort from November 2012 to February 2013 (82.6 %) voluntarily
participated. Students' motives to prepare and attend seminars were analyzed by
inspection of descriptive statistics. Linear regression analysis was conducted to
relate student preparation to the quality of seminars, seminar attendance to exam
scores, and exam scores to the quality of seminars. Answers to open questions
were deductively clustered. RESULTS: Studying the material, training for exams
and comparing answers with peers motivated students to prepare the seminars.
Students were motivated to participate actively because they wanted to keep track
of correct answers themselves, to better understand the content and to be able to
present their findings in plenary discussions. Perceived preparation of peers was
positively associated with the perceived quality of seminars. Also, seminar
attendance was positively associated with exam scores. Students' overall
explanations suggest that discussing with peers and applying knowledge in
pathophysiology cases underlies this association. CONCLUSION: Discussion with
well-prepared peers during seminars improves student perceptions of deeper
learning and peer-instructed seminar attendance was associated with higher exam
scores.
PMID- 27506462
TI - Impact of Three-Dimensional Printed Pelvicaliceal System Models on Residents'
Understanding of Pelvicaliceal System Anatomy Before Percutaneous
Nephrolithotripsy Surgery: A Pilot Study.
AB - OBJECTIVE: To investigate the impact of three-dimensional (3D) printed
pelvicaliceal system models on residents' understanding of pelvicaliceal system
anatomy before percutaneous nephrolithotripsy (PCNL). MATERIALS AND METHODS:
Patients with unilateral complex renal stones indicating PCNL were selected.
Usable data of patients were obtained from CT-scans in Digital Imaging and
Communications in Medicine (DICOM) format. Mimics software version 16.0
(Materialise, Belgium) was used for segmentation and extraction of pelvicaliceal
systems (PCSs). All DICOM-formatted files were converted to the stereolithography
file format. Finally, fused deposition modeling was used to create plasticine 3D
models of PCSs. A questionnaire was designed so that residents could assess the
3D models' effects on their understanding of the anatomy of the pelvicaliceal
system before PCNL (Fig. 3). RESULTS: Five patients' anatomically accurate models
of the human renal collecting system were effectively generated (Figs. 1 and 2).
After presentation of the 3D models, residents were 86% and 88% better at
determining the number of anterior and posterior calices, respectively, 60%
better at understanding stone location, and 64% better at determining optimal
entry calix into the collecting system (Fig. 5). CONCLUSION: Generating kidney
models of PCSs using 3D printing technology is feasible, and the models were
accepted by residents as aids in surgical planning and understanding of
pelvicaliceal system anatomy before PCNL.
PMID- 27506463
TI - Drug delivery into the cochlear apex: Improved control to sequentially affect
finely spaced regions along the entire length of the cochlear spiral.
AB - BACKGROUND: Administering pharmaceuticals to the scala tympani of the inner ear
is a common approach to study cochlear physiology and mechanics. We present here
a novel method for in vivo drug delivery in a controlled manner to sealed ears.
NEW METHOD: Injections of ototoxic solutions were applied from a pipette sealed
into a fenestra in the cochlear apex, progressively driving solutions along the
length of scala tympani toward the cochlear aqueduct at the base. Drugs can be
delivered rapidly or slowly. In this report we focus on slow delivery in which
the injection rate is automatically adjusted to account for varying cross
sectional area of the scala tympani, therefore driving a solution front at
uniform rate. RESULTS: Objective measurements originating from finely spaced, low
to high-characteristic cochlear frequency places were sequentially affected.
Comparison with existing methods(s): Controlled administration of pharmaceuticals
into the cochlear apex overcomes a number of serious limitations of previously
established methods such as cochlear perfusions with an injection pipette in the
cochlear base: The drug concentration achieved is more precisely controlled, drug
concentrations remain in scala tympani and are not rapidly washed out by
cerebrospinal fluid flow, and the entire length of the cochlear spiral can be
treated quickly or slowly with time. CONCLUSIONS: Controlled administration of
solutions into the cochlear apex can be a powerful approach to sequentially
effect objective measurements originating from finely spaced cochlear regions and
allows, for the first time, the spatial origin of CAPs to be objectively defined.
PMID- 27506464
TI - Pseudomonas aeruginosa colonization enhances ventilator-associated pneumonia
induced lung injury.
AB - BACKGROUND: Pseudomonas aeruginosa (PA) is the single-most common pathogen of
ventilator-associated pneumonia (VAP). Large quantities of PA in the trachea of
ventilated patients are associated with an increased risk of death. However, the
role of PA colonization in PA VAP-induced lung injury remains elusive. This study
examined the effect and mechanism of PA colonization in VAP-induced lung injury.
METHODS: C57BL/6 wild-type (WT) and c-Jun N-terminal kinase knockout (JNK1(-/-))
mice received mechanical ventilation for 3 h at 2 days after receiving nasal
instillation of PA (1 * 10(6) colony forming unit) or normal saline. RESULTS:
Intranasal instillation of PA or mechanical ventilation induced the expression of
interleukin-6 (IL-6) in the lungs. Phospho-JNK protein expression in the lungs
was significantly increased in mice receiving mechanical ventilation after PA
instillation as compared with those receiving ventilation alone. Mechanical
ventilation after PA instillation significantly increased the expression of tumor
necrosis factor-alpha (TNF-alpha), IL-1beta, and macrophage inflammatory protein
2 (MIP-2) proteins; neutrophil sequestration; and TNF-alpha, IL-1beta, and IL-6
levels in the lungs of WT mice, but not in JNK1(-/-) mice. CONCLUSION: PA
colonization plays an important role in PA VAP-induced lung injury through the
induction of JNK1-mediated inflammation. PA-induced VAP causes lung injury
through JNK signaling pathway in the lungs. JNK inhibition in ICU patients with
higher percentages of PA colonization may reduce VAP-induced lung injury and
mortality.
PMID- 27506465
TI - Maturation toward neuronal tissue in a Ewing sarcoma of bone after chemotherapy.
AB - BACKGROUND: Ewing sarcoma is the second most common bone tumor, occurring mainly
in children and young adults. It shows a typical primitive, small round cell
morphology and a characteristic fusion oncogene involving EWSR1 and members of
the ETS family in most of the cases. Neuronal maturation after chemotherapy is a
rare phenomenon and we herein describe such an exceptional case. CASE
PRESENTATION: An 8-year old boy was diagnosed with a Ewing sarcoma in the left
femur. On biopsy the morphology was typical and there was an EWSR1-FLI1 gene
fusion. He underwent neo-adjuvant chemotherapy and resection of the tumor. On
microscopic evaluation, part of the tumor showed ganglioneuroblastoma-like
differentiation with expression of neuronal markers. The continued presence of
EWSR1 rearrangement in both the blue round cell component and the
ganglioneuroblastoma-like component was shown by FISH analysis. CONCLUSIONS: In
conclusion, this case describes the possibility of a Ewing sarcoma to
differentiate into a ganglioneuroblastoma-like lesion after neo-adjuvant
chemotherapy treatment; the prognostic value of this phenomenon remains
questionable.
PMID- 27506467
TI - Realizing controllable graphene nucleation by regulating the competition of
hydrogen and oxygen during chemical vapor deposition heating.
AB - Oxygen can passivate Cu surface active sites when graphene nucleates. Thus, the
nucleation density is decreased. The CuO/Cu substrate was chosen for graphene
domain synthesis in our study. The results indicate that the CuO/Cu substrate is
beneficial for large-scale, single-crystal graphene domain synthesis. Graphene
grown on the CuO/Cu substrate exhibits fewer nucleation sites than on Cu foils,
suggesting that graphene follows an oxygen-dominating growth. Hydrogen treatment
via a heating process could weaken the surface oxygen's role in limiting graphene
nucleation under the competition of hydrogen and oxygen and could transfer the
synthesis of graphene into a hydrogen-dominating growth. However, the competition
only exists during the chemical vapor deposition heating process. For non
hydrogen heated samples, oxygen-dominating growth is experienced even though the
samples are annealed in hydrogen for a long time after the heating process. With
the temperature increases, the role of hydrogen gradually decreases. The balance
of hydrogen and oxygen is adjusted by introducing hydrogen gas at a different
heating temperatures. The oxygen concentration on the substrate surface is
believed to determine the reactions mechanisms based on the secondary ion mass
spectrometry test results. This study provides a new method for the controllable
synthesis of graphene nucleation during a heating process.
PMID- 27506466
TI - Menopause-induced uterine epithelium atrophy results from arachidonic
acid/prostaglandin E2 axis inhibition-mediated autophagic cell death.
AB - Women experience menopause later in life. Menopause is characterized by
dramatically decreased circulating estrogen level secondary to loss of ovarian
function and atrophic state of genital organs. However, the molecular mechanisms
for this process are not fully understood. In this study, we aimed to investigate
the potential molecular mechanisms that underlie menopause-induced uterine
endometrial atrophy. Our data showed that autophagy was activated in the uterine
epithelial cells of both ovariectomized rats and peri-menopausal females.
Endoplasmic reticulum (ER) stress occurred even prior to autophagy induction.
Integrated bioinformatics analysis revealed that ER stress induced downstream
decreased release of arachidonic acid (AA) and downregulation of AA/prostaglandin
E2 (PGE2) axis, which led to Akt/mTOR signaling pathway inactivation.
Consequently, autophagosomes were recruited and LC3-dependent autophagy was
induced in uterine epithelial cells. Treatment with exogenous E2, PGE2,
salubrinal or RNAi-mediated silencing of key autophagy genes could effectively
counteract estrogen depletion-induced autophagy. Collectively, autophagy is a
critical regulator of the uterine epithelium that accounts for endometrial
atrophy after menopause.
PMID- 27506468
TI - Needs among persons with human immunodeficiency virus and intellectual and
developmental disabilities in community mental health care: a cross-sectional
study.
AB - BACKGROUND: The experience of having human immunodeficiency virus (HIV) is often
associated with co-occurring mental health issues. Community mental health
services are an important source of support for persons with HIV living in the
community. Persons with intellectual disability (ID) are vulnerable to HIV and
may have unique support needs beyond those without ID receiving community care.
This study compared support needs of men with HIV in community mental health
programmes, with and without ID. METHODS: The sample was composed of 138 HIV
positive men with and without ID receiving mental health case management from one
community organisation in Ontario, Canada, on 31 March 2013. Staff-rated needs
across 16 domains grouped into four clusters were measured using the Camberwell
Assessment of Need: Basic needs (accommodation, food, public transportation,
money and benefits); self-care/functional needs (looking after the home, self
care and daytime activities); health/safety needs (physical health, psychological
distress, psychotic symptoms, safety to self and safety to others); and social
needs (company, intimate relationships and sexual expression). Adjusted logistic
regression models examined the association between ID and each need domain.
RESULTS: One-quarter of the sample (n = 34/138, 24.6%) had co-occurring ID. Those
with ID were more likely to have needs in the basic cluster [odds ratios: food
4.05 (1.14, 14.44), P:0.031; benefits 2.58 (1.05, 6.32), P:0.038)] and self
care/functional cluster [looking after the home (2.75 (1.17, 6.49), P:0.021);
self-care (2.72 (1.18, 6.27), P:0.019)], but were less likely to have need for
sexual expression: 0.35 (0.14,0.90), P:0.030) (social cluster). There were no
differences in the domains in the health/safety cluster. CONCLUSION: Despite
elevated cognitive needs in the basic and self-care/functional clusters for the
ID group, limited other differences suggest that with moderate additional
targeting, community mental health programmes for persons with HIV may be
appropriate for men with ID.
PMID- 27506469
TI - IPMiner: hidden ncRNA-protein interaction sequential pattern mining with stacked
autoencoder for accurate computational prediction.
AB - BACKGROUND: Non-coding RNAs (ncRNAs) play crucial roles in many biological
processes, such as post-transcription of gene regulation. ncRNAs mainly function
through interaction with RNA binding proteins (RBPs). To understand the function
of a ncRNA, a fundamental step is to identify which protein is involved into its
interaction. Therefore it is promising to computationally predict RBPs, where the
major challenge is that the interaction pattern or motif is difficult to be
found. RESULTS: In this study, we propose a computational method IPMiner
(Interaction Pattern Miner) to predict ncRNA-protein interactions from sequences,
which makes use of deep learning and further improves its performance using
stacked ensembling. One of the IPMiner's typical merits is that it is able to
mine the hidden sequential interaction patterns from sequence composition
features of protein and RNA sequences using stacked autoencoder, and then the
learned hidden features are fed into random forest models. Finally, stacked
ensembling is used to integrate different predictors to further improve the
prediction performance. The experimental results indicate that IPMiner achieves
superior performance on the tested lncRNA-protein interaction dataset with an
accuracy of 0.891, sensitivity of 0.939, specificity of 0.831, precision of 0.945
and Matthews correlation coefficient of 0.784, respectively. We further
comprehensively investigate IPMiner on other RNA-protein interaction datasets,
which yields better performance than the state-of-the-art methods, and the
performance has an increase of over 20 % on some tested benchmarked datasets. In
addition, we further apply IPMiner for large-scale prediction of ncRNA-protein
network, that achieves promising prediction performance. CONCLUSION: By
integrating deep neural network and stacked ensembling, from simple sequence
composition features, IPMiner can automatically learn high-level abstraction
features, which had strong discriminant ability for RNA-protein detection.
IPMiner achieved high performance on our constructed lncRNA-protein benchmark
dataset and other RNA-protein datasets. IPMiner tool is available at
http://www.csbio.sjtu.edu.cn/bioinf/IPMiner .
PMID- 27506470
TI - Colonization of toxigenic Clostridium difficile among ICU patients: a prospective
study.
AB - BACKGROUND: A prospective study was performed to investigate the prevalence of
colonization among ICU patients and to examine whether asymptomatic carriers were
the source of subsequent C. difficile infection (CDI) and acquisition of
toxigenic C. difficile. METHODS: Rectal swabs were collected from adult patients
on admission to and at discharge from a 50-bed medical ICU of a major referral
hospital in western China, from August to November 2014. Stools were collected
from patients who developed ICU-onset diarrhea. Both swabs and stools were
screened for tcdB (toxin B gene) by PCR. Samples positive to tcdB were cultured
for C. difficile and isolates recovered were screened for tcdB and the binary
toxin genes by PCR. Strain typing was performed using multilocus sequence typing
and isolates belonging to the same sequence type (ST) were further typed using
multiple-locus variable number tandem repeat analysis (MLVA). RESULTS: During the
4-month period, rectal swabs were collected from 360 (90.9 %) out of 396 patients
who were admitted to the ICU. Among the 360 patients, 314 had stayed in the ICU
more than 3 days, of which 213 (73.6 %) had a rectal swab collected within the 3
days prior to discharge from ICU. The prevalence of toxigenic C. difficile
colonization was 1.7 % (6 cases) and 4.3 % (10 cases) on admission and discharge,
respectively. Only four (1.1 %) out of 360 patients had CDI, corresponding to
10.7 cases per 10,000 ICU days. None of the four cases had toxigenic C. difficile
either on admission or at discharge. Toxigenic C. difficile isolates were
recovered from all swabs and stool samples positive for tcdB by PCR and belonged
to 7 STs (ST2, 3, 6, 37, 54, 103 and 129). None of the isolates belonging to the
same ST had identical MLVA patterns. Binary toxin genes were detected in one
ST103 isolate that caused colonization. CONCLUSION: The prevalence of
colonization with toxigenic C. difficile among patients on admission to ICU was
low in our setting. ICU-acquired toxigenic C. difficile were not linked to those
detected on admission. Active screening for toxigenic C. difficile may not be a
resource-efficient measure in settings with a low prevalence of colonization.
PMID- 27506471
TI - Academic nursing administrators' workplace satisfaction and intent to stay.
AB - BACKGROUND: In nursing education, the academic administrator is critical given
the multitude of challenges associated with program delivery (e.g., shortages of
faculty, strict and changing regulations for program accreditation, and the sheer
demand for more nurses). Unfortunately, with the focus on recruiting and
retaining new novice faculty to teach students, academic nursing administrators
have been overlooked in recent studies. PURPOSE: As such, this study aims to
explore the workplace satisfaction and intent to stay of academic nursing
administrators by considering their relation to a variety of demographic and work
related variables. METHODS: A secondary data source was used from the
Collaborative on Academic Careers in Higher Education (COACHE). One-way Analysis
of Variance (ANOVA) with post hoc Fisher's Least Significant Difference tests and
t-tests were used in the analysis. DISCUSSION/CONCLUSION: Results indicate that
several modifiable work factors positively relate to both job satisfaction and
intent to stay.
PMID- 27506472
TI - Analysis Method for Quantifying the Morphology of Nanotube Networks.
AB - While atomic force microscopy (AFM) is a powerful technique for imaging
assemblies and networks of nanoscale materials, approaches for quantitative
assessment of the morphology of these materials are lacking. Here we present a
volume-based approach for analyzing AFM images of assemblies of nano-objects that
enables the extraction of relevant parameters describing their morphology. Random
networks of single-walled carbon nanotubes (SWCNTs) deposited via solution-phase
processing are used as an example to develop the method and demonstrate its
utility. AFM imaging shows that the morphology of these networks depends on
details of processing and is influenced by choice of substrate, substrate
cleaning method, and postdeposition rinsing protocols. A method is outlined to
analyze these images and extract relevant parameters describing the network
morphology such as the density of SWCNTs and the degree to which tubes are
bundled. Because this volume-based approach depends on accurate measurements of
the height of individual tubes and their networks, a procedure for obtaining
reliable height measurements is also discussed. Obtaining quantitative parameters
that describe the network morphology allows going beyond qualitative descriptions
of images and will facilitate optimizing network preparation methods based on
measurable criteria and correlating performance with morphology.
PMID- 27506473
TI - In vitro selection and evolution.
PMID- 27506474
TI - Fatty acid alterations in the detritivorous Prochilodus lineatus promoted by
opportunistic feeding on sewage discharges in the Rio de la Plata estuary.
AB - Muscle fatty acid profiles and PCB contents of the detritivorous species
Prochilodus lineatus and its diet (stomach contents, settling particles and
sediments) were analysed from reference and polluted areas of the Parana-Rio de
la Plata basin, to evaluate the alterations produced by opportunistic feeding on
sewage discharges. Overall muscle fatty acid composition was dominated by
saturated and monounsaturated 16 and 18 carbon (18 C-FA) components with reduced
long-chain polyunsaturated fatty acids (LC-PUFA). Compared to sediments, settling
particles and stomach contents were enriched in lipids and had a similar fatty
acid composition. Opportunistic feeding on sewage detritus at Buenos Aires
resulted in enhanced PCB and triglyceride accumulation, with higher proportions
of 18 C-FA and lower proportions of 16:1 and LC-PUFA compared to fish from
northern pristine reaches of the basin. Mid-Parana showed intermediate values
reflecting mixing of the North stock with migrating Buenos Aires P. lineatus
identified by their lipid and contaminant profile. According to multivariate
analyses, this geographical variation of fatty acid composition was strongly
influenced by PCB concentration. Prochilodus lineatus assimilates the energy
subsidy of sewage inputs through enhanced lipogenesis with dominant 18 C-FA and
significant amounts of valuable LC-PUFA. This lipid alteration facilitates the
bioaccumulation of PCBs which in turn may reinforce the adipogenic effect of
sewage feeding.
PMID- 27506475
TI - GSH Induced Controlled Release of Levofloxacin from a Purpose-Built Prodrug:
Luminescence Response for Probing the Drug Release in Escherichia coli and
Staphylococcus aureus.
AB - Fluoroquinolones are third-generation broad spectrum bactericidal antibiotics and
work against both Gram-positive and Gram-negative bacteria. Levofloxacin (L), a
fluoroquinolone, is widely used in anti-infective chemotherapy and treatment of
urinary tract infection and pneumonia. The main pathogen for urinary tract
infections is Escherichia coli, and Streptococcus pneumoniae is responsible for
pneumonia, predominantly a lower respiratory tract infection. Poor permeability
of L leads to the use of higher dose of this drug and excess drug in the outer
cellular fluid leads to central nervous system (CNS) abnormality. One way to
counter this is to improve the lipophilicity of the drug molecule, and
accordingly, we have synthesized two new Levofloxacin derivatives, which
participated in the spatiotemporal release of drug via disulfide bond cleavage
induced by glutathione (GSH). Recent studies with Streptococcus mutants suggest
that it is localized in epithelial lining fluid (ELF) of the normal lower
respiratory tract and the effective [GSH] in ELF is ~430 MUM. E. coli typically
cause urinary tract infections and the concentration of GSH in porcine bladder
epithelium is reported as 0.6 mM for a healthy human. Thus, for the present study
we have chosen two important bacteria (Gram + ve and Gram - ve), which are
operational in regions having high extracellular GSH concentration.
Interestingly, this supports our design of new lipophilic Levofloxacin based
prodrugs, which released effective drug on reaction with GSH. Higher
lipophilicity favored improved uptake of the prodrugs. Site specific release of
the drug (L) could be achieved following a glutathione mediated biochemical
transformation process through cleavage of a disulfide bond of these purpose
built prodrugs. Further, appropriate design helped us to demonstrate that it is
possible also to control the kinetics of the drug release from respective
prodrugs. Associated luminescence enhancement helps in probing the release of the
drug from the prodrug in bacteria and helps in elucidating the mechanistic
pathway of the transformation. Such an example is scarce in the contemporary
literature.
PMID- 27506476
TI - Casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorates high glucose
induced insulin resistance in HepG2 cells via activation of AMPK signaling.
AB - SCOPE: Recently, casein glycomacropeptide (GMP)-derived peptide was found to
possess potent antioxidant and anti-inflammatory activities. In this study, the
improvement effects and underlying molecular mechanisms of GMP-derived peptide on
hepatic insulin resistance were investigated. METHODS AND RESULTS: The peptide
IPPKKNQDKTE was identified from GMP papain hydrolysates by LC-ESI-MS/MS. Effects
of IPPKKNQDKTE on glucose metabolism and expression levels of the hepatic insulin
signaling proteins in high glucose-induced insulin-resistant HepG2 cells were
evaluated. Results showed that IPPKKNQDKTE dose-dependently increased glucose
uptake and intracellular glycogen in insulin-resistant HepG2 cells without
affecting cell viability. IPPKKNQDKTE increased the phosphorylation of Akt and
GSK3beta and decreased the expression levels of p-GS, G6Pase and PEPCK. These
IPPKKNQDKTE-mediated protection effects were reversed by PI3K/Akt inhibitor
LY294002, showing the mediatory role of PI3K/Akt. Moreover, treatment with
IPPKKNQDKTE reduced IRS-1 Ser307 phosphorylation and increased phosphorylation of
AMPK. Knockdown AMPK using siRNA in HepG2 cells increased Ser307 phosphorylation
of IRS-1 and reduced Akt phosphorylation in IPPKKNQDKTE-treated insulin-resistant
cells. CONCLUSION: IPPKKNQDKTE prevents high glucose-induced insulin resistance
in HepG2 cells by modulating the IRS-1/PI3K/Akt signaling pathway through AMPK
activation, indicating that IPPKKNQDKTE plays a potential role in the prevention
and treatment of hepatic insulin resistance and type 2 diabetes.
PMID- 27506478
TI - Prevalence of potentially inappropriate prescribing among older adults: A
comparison of the Beers 2012 and Screening Tool of Older Person's Prescriptions
criteria version 2.
AB - AIM: To date, there is no study comparing the Beers 2012 and Screening Tool of
Older Person's Prescriptions (STOPP) version 2 criteria, nor reporting a
comparison of the prevalence of potentially inappropriate Prescribing (PIM) with
STOPP version 2. We aimed to evaluate the prescriptions of patients admitted to a
geriatric outpatient clinic with these tools, and to document the factors related
to PIM use. METHODS: Older patients (aged >=65 years) admitted to the outpatient
clinic of a university hospital were retrospectively evaluated for PIM with Beers
2012 and STOPP version 2 criteria. Age; sex; chronic disease and number of drugs;
and functional, depression and nutritional statuses were studied with regression
analysis as possible factors related to PIM. RESULTS: The study included 667
participants (63.1% women, mean age 77.6 +/- 6.3 years). The mean number of drugs
was 6.1 +/- 3.4. PIM prevalence detected by STOPP version 2 was higher than that
of the Beers 2012 criteria (39.1% vs 33.3%, respectively; P < 0.001; Z = -3.5)
with moderate agreement in between (kappa = 0.44). Antipsychotics, over-the
counter vitamin/supplements, aspirin, selective-serotonin-reuptake-inhibitors and
anticholinergics were the leading drug classes for PIM. The extent of
polypharmacy (P < 0.001, OR 1.29, 95% CI 1.20-1.38) was the most important
variable related to PIM, along with the multiple comorbidities (P = 0.005, OR
1.16, 95% CI 1.05-1.30). Higher level of functionality was inversely associated
with PIM (P = 0.009, OR 0.90, 95% CI 0.83-0.97). CONCLUSIONS: Inappropriate
prescription prevalence of ~40% by STOPP version 2 was similar to the global
worldwide prevalence - yet at the upper end. STOPP version 2 was more successful
than Beers 2012 to detect PIM. Patients with multiple drug use, multiple
comorbidities and more dependency were more likely to have PIM requiring special
attention during prescription. Geriatr Gerontol Int 2017; 17: 1245-1251.
PMID- 27506479
TI - Birthweight percentiles for twin birth neonates by gestational age in China.
AB - Localized birthweight references for gestational ages serve as an essential tool
in accurate evaluation of atypical birth outcomes. Such references for twin
births are currently not available in China. The aim of this study was to
construct up-to-data sex specific birth weight references by gestational ages for
twin births in China. We conducted a population-based analysis on the data of
22,507 eligible living twin infants with births dated between 8/01/2006 and
8/31/2015 from all 95 hospitals within the Wuhan area. Gestational ages in
complete weeks were determined using a combination of last-menstrual-period based
(LMP) estimation and ultrasound examination. Smoothed percentile curves were
created by the Lambda Mu Sigma (LMS) method. Reference of the 3(rd), 10(th),
25(th), 50(th), 75(th), 90(th), 97(th) percentiles birth weight by sex and
gestational age were made using 11,861 male and 10,646 female twin newborns with
gestational age 26-42 weeks. Separate birthweight percentiles curves for male and
female twins were constructed. In summary, our study firstly presents percentile
curves of birthweight by gestational age for Chinese twin neonates. Further
research is required for the validation and implementation of twin birthweight
curves into clinical practice.
PMID- 27506481
TI - Sufficient dimension reduction for censored predictors.
AB - Motivated by a study conducted to evaluate the associations of 51 inflammatory
markers and lung cancer risk, we propose several approaches of varying
computational complexity for analyzing multiple correlated markers that are also
censored due to lower and/or upper limits of detection, using likelihood-based
sufficient dimension reduction (SDR) methods. We extend the theory and the
likelihood-based SDR framework in two ways: (i) we accommodate censored
predictors directly in the likelihood, and (ii) we incorporate variable
selection. We find linear combinations that contain all the information that the
correlated markers have on an outcome variable (i.e., are sufficient for modeling
and prediction of the outcome) while accounting for censoring of the markers.
These methods yield efficient estimators and can be applied to any type of
outcome, including continuous and categorical. We illustrate and compare all
methods using data from the motivating study and in simulations. We find that
explicitly accounting for the censoring in the likelihood of the SDR methods can
lead to appreciable gains in efficiency and prediction accuracy, and also
outperformed multiple imputations combined with standard SDR.
PMID- 27506482
TI - Enemas, suppositories and rectal stimulation are not effective in accelerating
enteral feeding or meconium evacuation in low-birthweight infants: a systematic
review.
AB - : Early full enteral feeding in preterm infants decreases morbidity and
mortality. Our systematic review covered the effectiveness of rectal stimulation,
suppositories and enemas on stooling patterns and feeding tolerance in low
birthweight infants born at up to 32 weeks. It comprised seven studies published
between 2007 and 2014 and covered 495 infants. CONCLUSION: Suppositories were
ineffective in shortening the time to reach full enteral feeding, and the
evidence on enemas was contradictory. Enemas and rectal stimulation did not
shorten the time until complete meconium evacuation was reached. Further research
into safe, effective interventions to accelerate meconium excretion is needed.
PMID- 27506483
TI - Alterations of the Lamina Cribrosa Are Associated with Peripapillary
Retinoschisis in Glaucoma and Pachychoroid Spectrum Disease.
AB - PURPOSE: To describe the findings of enhanced depth imaging (EDI) optical
coherence tomography (OCT) of the lamina cribrosa (LC) in glaucoma and
pachychoroid spectrum diseases associated with peripapillary retinoschisis.
DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 16
patients from 1 institution. METHODS: Detailed medical case histories, optic disc
and retinal imaging with EDI using the Spectralis OCT (Heidelberg Engineering,
Heidelberg, Germany), and clinical course were reviewed for patients with
peripapillary retinoschisis without a known predisposing condition. MAIN OUTCOME
MEASURES: Clinical features and findings of the EDI OCT. RESULTS: Among the 16
eyes with peripapillary retinoschisis that had abnormal findings on EDI of the
LC, 8 had glaucoma and 8 had pachychoroid spectrum diseases, including chronic
central serous chorioretinopathy (CSC) (6 eyes), small pigment epithelium
detachment (1 eye), and polypoidal choroidal vasculopathy (PCV) (1 eye). The
abnormal LC findings were central or peripheral focal LC defects in eyes with
glaucoma and LC disinsertions or peripheral focal LC defects in eyes with
pachychoroid spectrum diseases. Central LC defects were related to inner layer
retinoschisis, whereas LC disinsertions and peripheral LC defects were related to
outer layer retinoschisis. The peripapillary retinoschisis did not show a
topographic association with the underlying chronic CSC- or PCV-associated
lesions. In 6 treated eyes with pachychoroid, peripapillary retinoschisis
resolved along with subretinal fluid after anti-vascular endothelial growth
factor injection in 4 eyes, whereas retinoschisis persisted after the resolution
of subretinal fluid in 2 eyes. CONCLUSIONS: Enhanced depth imaging OCT of the LC
demonstrated alterations associated with peripapillary retinoschisis,
pachychoroid spectrum diseases, and glaucoma.
PMID- 27506484
TI - Chronic Vascular Arrest as a Predictor of Bevacizumab Treatment Failure in
Retinopathy of Prematurity.
AB - PURPOSE: To describe a pattern of retinopathy of prematurity (ROP) disease
regression and chronic vascular arrest after intravitreal bevacizumab treatment
that is not observed after peripheral laser ablation. DESIGN: Single-institution
retrospective cohort study. PARTICIPANTS: Consecutive sample of 58 eyes in 30
patients treated for type 1 ROP. METHODS: Initial treatment with either a single
intravitreal injection of bevacizumab in off-label use (n = 33 eyes) or
peripheral laser ablation (n = 25 eyes) as part of standard clinical care. There
was bias in recommending off-label bevacizumab for smaller infants with type 1
ROP. MAIN OUTCOME AND MEASURES: Reactivation or persistence of ROP, as determined
by clinical examination, fundus photography, and fluorescein angiography.
RESULTS: All eyes treated initially with bevacizumab demonstrated irregular
progression of the leading vascular edge in a stereotyped pattern, suggestive of
scalloped regression. Recurrence, based on angiographic demonstration of leakage,
or chronic vascular arrest, confirmed based on angiographic demonstration of
peripheral ischemia, was noted in 30 eyes (91%) in the bevacizumab group, at a
median interval of 14.9 weeks after injection (corrected gestational age, 49.3
weeks). Univariate logistic regression indicated that the need for rescue
treatment was associated with decreased birth weight (odds ratio [OR], -0.007; P
= 0.04) and age of initial treatment (OR, -0.35; P = 0.05), but not gender, race,
or gestational age. Multivariate logistic regression indicated that only
decreased birth weight (OR, -0.018; P = 0.04) was associated with need for rescue
treatment. CONCLUSIONS: Treating ROP with intravitreal bevacizumab results in a
characteristic scalloped regression pattern that is highly associated with
treatment using biologic anti-vascular endothelial growth factor agents. The
presence of this pattern in conjunction with chronic vascular arrest and
peripheral retinal ischemia persisting beyond standard screening timelines has
significant implications for the management of ROP. Fluorescein angiography is
important in assessing vascular maturation in these infants.
PMID- 27506485
TI - A Randomized Trial Evaluating Short-term Effectiveness of Overminus Lenses in
Children 3 to 6 Years of Age with Intermittent Exotropia.
AB - PURPOSE: To evaluate the short-term effectiveness of overminus spectacles in
improving control of childhood intermittent exotropia (IXT). DESIGN: Randomized,
clinical trial. PARTICIPANTS: A total of 58 children aged 3 to <7 years with IXT.
Eligibility criteria included a distance control score of 2 or worse (mean of 3
measures during a single examination) on a scale of 0 (exophoria) to 5 (constant
exotropia) and spherical equivalent refractive error between -6.00 diopters (D)
and +1.00 D. METHODS: Children were randomly assigned to overminus spectacles (
2.50 D over cycloplegic refraction) or observation (non-overminus spectacles if
needed or no spectacles) for 8 weeks. MAIN OUTCOME MEASURES: The primary outcome
was distance control score for each child (mean of 3 measures during a single
examination) assessed by a masked examiner at 8 weeks. Outcome testing was
conducted with children wearing their study spectacles or plano spectacles for
the children in the observation group who did not need spectacles. The primary
analysis compared mean 8-week distance control score between treatment groups
using an analysis of covariance model that adjusted for baseline distance
control, baseline near control, prestudy spectacle wear, and prior IXT treatment.
Treatment side effects were evaluated using questionnaires completed by parents.
RESULTS: At 8 weeks, mean distance control was better in the 27 children treated
with overminus spectacles than in the 31 children who were observed without
treatment (2.0 vs. 2.8 points, adjusted difference = -0.75 points favoring the
overminus group; 2-sided 95% confidence interval, -1.42 to -0.07 points). Side
effects of headaches, eyestrain, avoidance of near activities, and blur appeared
similar between treatment groups. CONCLUSIONS: In a pilot randomized clinical
trial, overminus spectacles improved distance control at 8 weeks in children aged
3 to <7 years with IXT. A larger and longer randomized trial is warranted to
assess the effectiveness of overminus spectacles in treating IXT, particularly
the effect on control after overminus treatment has been discontinued.
PMID- 27506486
TI - Two-Year COMPASS Trial Results: Supraciliary Microstenting with
Phacoemulsification in Patients with Open-Angle Glaucoma and Cataracts.
AB - PURPOSE: We evaluated 2-year safety and efficacy of supraciliary microstenting
(CyPass Micro-Stent; Transcend Medical, Inc., Menlo Park, CA) for treating mild
to-moderate primary open-angle glaucoma (POAG) in patients undergoing cataract
surgery. DESIGN: Multicenter (24 US sites), interventional randomized clinical
trial (RCT) (ClinicalTrials.gov identifier, NCT01085357). PARTICIPANTS: Subjects
were enrolled beginning July 2011, with study completion in March 2015. Subjects
had POAG with mean diurnal unmedicated intraocular pressure (IOP) 21-33 mmHg and
were undergoing phacoemulsification cataract surgery. METHODS: After completing
cataract surgery, subjects were intraoperatively randomized to
phacoemulsification only (control) or supraciliary microstenting with
phacoemulsification (microstent) groups (1:3 ratio). Microstent implantation via
an ab interno approach to the supraciliary space allowed concomitant cataract and
glaucoma surgery. MAIN OUTCOME MEASURES: Outcome measures included percentage of
subjects achieving >=20% unmedicated diurnal IOP lowering versus baseline, mean
IOP change and glaucoma medication use, and ocular adverse event (AE) incidence
through 24 months. RESULTS: Of 505 subjects, 131 were randomized to the control
group and 374 were randomized to the microstent group. Baseline mean IOPs in the
control and microstent groups were similar: 24.5+/-3.0 and 24.4+/-2.8 mmHg,
respectively (P > 0.05); mean medications were 1.3+/-1.0 and 1.4+/-0.9,
respectively (P > 0.05). There was early and sustained IOP reduction, with 60% of
controls versus 77% of microstent subjects achieving >=20% unmedicated IOP
lowering versus baseline at 24 months (P = 0.001; per-protocol analysis). Mean
IOP reduction was ?7.4 mmHg for the microstent group versus ?5.4 mmHg in controls
(P < 0.001), with 85% of microstent subjects not requiring IOP medications at 24
months. Mean 24-month medication use was 67% lower in microstent subjects (P <
0.001); 59% of control versus 85% of microstent subjects were medication free.
Mean medication use in controls decreased from 1.3+/-1.0 drugs at baseline to
0.7+/-0.9 and 0.6+/-0.8 drugs at 12 and 24 months, respectively, and in the
microstent group from 1.4+/-0.9 to 0.2+/-0.6 drugs at both 12 and 24 months (P <
0.001 for reductions in both groups at both follow-ups vs. baseline). No vision
threatening microstent-related AEs occurred. Visual acuity was high in both
groups through 24 months; >98% of all subjects achieved 20/40 best-corrected
visual acuity or better. CONCLUSIONS: This RCT demonstrated safe and sustained 2
year reduction in IOP and glaucoma medication use after microinterventional
surgical treatment for mild-to-moderate POAG.
PMID- 27506487
TI - Risk Alleles Associated with Neovascularization in a Pachychoroid Phenotype.
PMID- 27506488
TI - Clinical and Genetic Features of Choroideremia in Childhood.
AB - PURPOSE: To review the functional and anatomic characteristics of choroideremia
in the pediatric population, aiming to describe the earliest features of the
disease and to identify biomarkers useful for monitoring disease progression.
DESIGN: Retrospective case series. PARTICIPANTS: Children diagnosed with
choroideremia at a single institution. METHODS: Patients were identified using an
electronic patient record system. Case notes and retinal imaging (color fundus
photography [CFP], spectral-domain [SD] optical coherence tomography [OCT], and
fundus autofluorescence [FAF]) then were reviewed. The results of genetic testing
also were recorded. MAIN OUTCOME MEASURES: Presenting symptoms, visual acuity,
fundus changes (CFP, SD OCT, FAF), and CHM sequencing results. RESULTS: Twenty
nine patients were identified with a mean age at referral of 9 years (range, 3-16
years). CHM mutations were identified in 15 of 19 patients tested. Nyctalopia was
the predominant symptom (66%). Five of 29 patients were asymptomatic at
presentation. At the final follow-up visit (mean age, 16 years; range, 7-26
years), most maintained excellent visual acuity (mean, 0.98+/-0.13 decimalized
Snellen acuity). The first sign of retinopathy was widespread pigment clumping at
the level of the retinal pigment epithelium (RPE). This later evolved to
chorioretinal atrophy, most marked in the mid-peripheral retina. Peripapillary
atrophy also was an early feature and was progressive in nature. Three different
zones of FAF change were visible. Persistence of the inner retinal layers,
detected by SD OCT, was visible at presentation in 15 of 27 patients. Subfoveal
choroidal thickness decreased with age, whereas central retinal thickness
increased over a similar interval. Four patients in whom visual acuity decreased
over the follow-up period recorded a reduction in central retinal thickness.
CONCLUSIONS: Progressive structural changes occur at a time when central visual
function is maintained. Pigmentary changes at the level of the RPE occur early in
the disease course. Peripapillary chorioretinal atrophy, central retinal
thickness, and subfoveal choroidal thickness are likely to be valuable in
monitoring disease progression and should be considered as potential biomarkers
in future therapeutic trials.
PMID- 27506489
TI - Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With
Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung
Cancer Study Group Trial OLCSG 1403.
AB - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as
first-line therapy for patients with EGFR-mutated non-small-cell lung cancer
(NSCLC) have shown a significantly better objective response rate and progression
free survival than platinum doublet therapy. However, acquired resistance often
occurs within 12 months. One of the potential strategies for treating acquired
resistance in NSCLC is the readministration of EGFR-TKIs, a strategy that has
mainly been evaluated using gefitinib or erlotinib. The aim of the present study
is to investigate the efficacy and safety of EGFR-TKI readministration with
afatinib in patients with advanced NSCLC harboring activating EGFR mutations
without T790M. The primary endpoint is progression-free survival. The secondary
endpoints include the objective response rate, disease control rate, overall
survival, toxicity, and quality of life. A total of 12 patients will be enrolled
in this trial.
PMID- 25754364
TI - Photoacoustic imaging platforms for multimodal imaging.
AB - Photoacoustic (PA) imaging is a hybrid biomedical imaging method that exploits
both acoustical and optical properties and can provide both functional and
structural information. Therefore, PA imaging can complement other imaging
methods, such as ultrasound imaging, fluorescence imaging, optical coherence
tomography, and multi-photon microscopy. This article reviews techniques that
integrate PA with the above imaging methods and describes their applications.
PMID- 27506491
TI - Understanding the Correlates of Face-to-Face and Cyberbullying Victimization
Among U.S. Adolescents: A Social-Ecological Analysis.
AB - Using a national sample of 7,533 U.S. adolescents in grades 6-10, this study
compares the social-ecological correlates of face-to-face and cyberbullying
victimization. Results indicate that younger age, male sex, hours spent on social
media, family socioeconomic status (SES; individual context), parental monitoring
(family context), positive feelings about school, and perceived peer support in
school (school context) were negatively associated with both forms of
victimization. European American race, Hispanic/Latino race (individual), and
family satisfaction (family context) were all significantly associated with less
face-to-face victimization only, and school pressure (school context) was
significantly associated with more face-to-face bullying. Peer groups accepted by
parents (family context) were related to less cyberbullying victimization, and
calling/texting friends were related to more cyberbullying victimization.
Research and practice implications are discussed.
PMID- 27506493
TI - Seasonal immunohistochemical reactivity of S-100 and alpha-smooth muscle actin
proteins in the epididymis of dromedary camel, Camelus dromedarius.
AB - The S-100 and alpha smooth muscle actin (alpha-SMA) proteins have been localised
in epididymal tissue of several mammalian species, but there have been no data
for a seasonal work in camel. The aim of this study was to investigate the
immunoreactivities of S-100 and alpha-SMA proteins in the epididymis of dromedary
camel during breeding and nonbreeding seasons. The immunopositive signals for
both proteins were observed in different regions of camel epididymis. S-100
immunopositive signals were noted in both the epididymal epithelium and the
intertubular connective tissue, while alpha-SMA signals were confined to the
intertubular connective tissue, especially in the peritubular smooth muscle coat
and the blood vessels. This study showed an increase in the intensity of S-100
and alpha-SMA immunoreactions during the breeding season in different regions of
camel epididymis than that seen in the nonbreeding season. In conclusion,
epididymis might be considered as a source of S-100 and alpha-SMA proteins in the
camel and the secretion of these proteins showed distinct seasonal variations.
Further, S-100 and alpha-SMA may affect the structural and physiological states
of the epididymal duct.
PMID- 27506492
TI - KV 7/M channels as targets for lipopolysaccharide-induced inflammatory neuronal
hyperexcitability.
AB - KEY POINTS: Neuroinflammation associated with CNS insults leads to neuronal
hyperexcitability, which may culminate in epileptiform discharges. Application of
the endotoxin lipopolysaccharide (LPS) to brain tissue initiates a
neuroinflammatory cascade, providing an experimental model to study the
mechanisms of neuroinflammatory neuronal hyperexcitability. Here we show that LPS
application to hippocampal slices markedly enhances the excitability of CA1
pyramidal cells by inhibiting a specific potassium current, the M-current,
generated by KV 7/M channels, which controls the excitability of almost every
neuron in the CNS. The LPS-induced M-current inhibition is triggered by
sequential activation of microglia, astrocytes and pyramidal cells, mediated by
metabotropic purinergic and glutamatergic transmission, leading to blockade of KV
7/M channels by calcium released from intracellular stores. The identification of
the downstream molecular target of neuroinflammation, namely the KV 7/M channel,
potentially has far reaching implications for the understanding and treatment of
many acute and chronic brain disorders. ABSTRACT: Acute brain insults and many
chronic brain diseases manifest an innate inflammatory response. The hallmark of
this response is glia activation, which promotes repair of damaged tissue, but
also induces structural and functional changes that may lead to an increase in
neuronal excitability. We have investigated the mechanisms involved in the
modulation of neuronal activity by acute inflammation. Initiating inflammatory
responses in hippocampal tissue rapidly led to neuronal depolarization and
repetitive firing even in the absence of active synaptic transmission. This
action was mediated by a complex metabotropic purinergic and glutamatergic glia
to-neuron signalling cascade, leading to the blockade of neuronal KV 7/M channels
by Ca2+ released from internal stores. These channels generate the low voltage
activating, non-inactivating M-type K+ current (M-current) that controls
intrinsic neuronal excitability, and its inhibition was the predominant cause of
the inflammation-induced hyperexcitability. Our discovery that the ubiquitous KV
7/M channels are the downstream target of the inflammation-induced cascade, has
far reaching implications for the understanding and treatment of many acute and
chronic brain disorders.
PMID- 27506494
TI - In vitro Characterization of Phenylacetate Decarboxylase, a Novel Enzyme
Catalyzing Toluene Biosynthesis in an Anaerobic Microbial Community.
AB - Anaerobic bacterial biosynthesis of toluene from phenylacetate was reported more
than two decades ago, but the biochemistry underlying this novel metabolism has
never been elucidated. Here we report results of in vitro characterization
studies of a novel phenylacetate decarboxylase from an anaerobic, sewage-derived
enrichment culture that quantitatively produces toluene from phenylacetate;
complementary metagenomic and metaproteomic analyses are also presented. Among
the noteworthy findings is that this enzyme is not the well-characterized
clostridial p-hydroxyphenylacetate decarboxylase (CsdBC). However, the toluene
synthase under study appears to be able to catalyze both phenylacetate and p
hydroxyphenylacetate decarboxylation. Observations suggesting that phenylacetate
and p-hydroxyphenylacetate decarboxylation in complex cell-free extracts were
catalyzed by the same enzyme include the following: (i) the specific activity for
both substrates was comparable in cell-free extracts, (ii) the two activities
displayed identical behavior during chromatographic separation of cell-free
extracts, (iii) both activities were irreversibly inactivated upon exposure to
O2, and (iv) both activities were similarly inhibited by an amide analog of p
hydroxyphenylacetate. Based upon these and other data, we hypothesize that the
toluene synthase reaction involves a glycyl radical decarboxylase. This first
time study of the phenylacetate decarboxylase reaction constitutes an important
step in understanding and ultimately harnessing it for making bio-based toluene.
PMID- 27506495
TI - Absorber modeling for NGCC carbon capture with aqueous piperazine.
AB - A hybrid system combining amine scrubbing with membrane technology for carbon
capture from natural gas combined cycle (NGCC) power plants is proposed in this
paper. In this process, the CO2 in the flue gas can be enriched from 4% to 18% by
the membrane, and the amine scrubbing system will have lower capture costs.
Aqueous piperazine (PZ) is chosen as the solvent. Different direct contact cooler
(DCC) options, multiple absorber operating conditions, optimal intercooling
designs, and different cooling options have been evaluated across a wide range of
inlet CO2. Amine scrubbing without DCC is a superior design for NGCC carbon
capture. Pump-around cooling at the bottom of the absorber can effectively manage
the temperature of the hot flue gas, and still be effective for CO2 absorption.
The absorber gas inlet must be designed to avoid excessive localized temperature
and solvent evaporation. When the inlet CO2 increases from 4% to 18%, total
absorber CAPEX decreases by 60%; another 10% of the total absorber CAPEX can be
saved by eliminating the DCC. In-and-out intercooling works well for high CO2,
while pump-around intercooling is more effective for low CO2. Dry cooling
requires more packing and energy but appears to be technically and economically
feasible if cooling water availability is limited.
PMID- 27506496
TI - A Functional Polymorphism (rs937283) in the MDM2 Promoter Region is Associated
with Poor Prognosis of Retinoblastoma in Chinese Han Population.
AB - The effect of single nucleotide polymorphisms (SNPs) at MDM2 has been
investigated in several cancer types. Three MDM2 SNPs(rs937283, rs2270744 and
rs769412) have previously been suggested to be positively correlated with cancer.
In this study, we aimed to explore the association of rs937283, rs2270744 and
rs769412 polymorphisms with retinoblastoma (RB) risk, clinicopathological
characteristics, and prognosis. Compared with wild-type genotype AA at rs937283,
individuals carrying AG and GG genotype had a significantly increased risk for
developing RB (OR = 1.86, 95% CI 1.13-3.08; OR = 2.48, 95% CI 1.10-5.62,
respectively). RB patients with allele G at rs937283 were more susceptible to
invasion and high tumor aggression (OR = 2.42, 95% CI 1.43-4.11; OR = 2.15, 95%
CI 1.27-3.64, respectively). Kaplan-Meier curves and log-rank results revealed
that RB patients harboring genotype GG and G allele at rs937283 had worse
survival (P < 0.02 and P < 0.01, respectively). In addition, the A to G
substitution at rs937283 significantly enhanced the transcription activity of the
MDM2 gene in vitro. In vivo, we found that MDM2 mRNA and protein were
overexpressed in individuals who carried the G allele at rs937283. This study
suggested that the MDM2 rs937283 polymorphism is a novel functional SNP both in
vitro and in vivo as well as a biomarker for poor prognosis in RB.
PMID- 27506497
TI - Challenges and successes for the grantees and the Technical Advisory Group of
WHO's influenza vaccine technology transfer initiative.
AB - One of the aims of the WHO Global Action Plan for Influenza Vaccines (GAP) was to
transfer influenza vaccine production technology to interested manufacturers and
governments in developing countries, to enable greater influenza vaccine
manufacturing capacity against any pandemic threat or pandemic. For this
objective, the GAP was supported by an independent Technical Advisory Group (TAG)
to assist WHO to select vaccine manufacturing proposals for funding and to
provide programmatic support for successful grantees. While there were many
challenges, for both the TAG and grantees, there were also notable successes with
an additional capacity of 338-600 million pandemic vaccine doses being made
possible by the programme between 2007 and 2015, and a potential capacity of more
than 600 million by 2016/17 with up to one billion doses expected by 2018/19.
Seasonal vaccine production was also developed in 4 countries with another 4-5
countries expected to be producing seasonal vaccine by 2018/19. The relatively
small WHO investments - in time and funding - made in these companies to develop
their own influenza vaccine production facilities have had quite dramatic
results.
PMID- 27506498
TI - Preventing further misuse of the ELISA technique and misinterpretation of
serological antibody assay data.
AB - The indirect ELISA is a widely utilized method to assay serum antibodies.
However, a common and critical problem when analyzing serum antibodies is the
disregard for the background noise reaction caused by the hydrophobic binding of
immunoglobulin components in serum components to plastic. Unfortunately, current
blocking agents cannot prevent this background noise reaction. To prevent further
misuse of the ELISA technique, it is important to openly discuss the fundamental
problems involved in the ELISA system.
PMID- 27506499
TI - Keloidectomy with core fillet flap and intralesional verapamil injection for
recurrent earlobe keloids.
AB - BACKGROUND: Earlobe keloids are usually recalcitrant to treatment and have a high
rate of recurrence. Verapamil is a calcium channel antagonist that has been shown
to inhibit the synthesis/secretion of extracellular matrix molecules and increase
collagenase. OBJECTIVES: This prospective study was designed to evaluate the
results of treatment of recurrent earlobe keloids using keloidectomy with core
fillet flap and intralesional verapamil injection. METHODS: Nineteen keloids in
16 patients were treated using this technique with intralesional verapamil
injection given intraoperatively, then every 2 weeks for 3 months, with
postoperative follow-up for 18 months. RESULTS: Fourteen patients completed the
study. Ten patients (71.4%) showed response to treatment. Four (28.6%) cases
showed recurrence, two (14.2%) at the wound bed and another two (14. 2%) at the
incision line. Eighty percent of responders were highly satisfied with their
treatment. CONCLUSION: Keloidectomy with core fillet flap and intralesional
verapamil injection is a reliable and cost-effective method in the treatment of
recurrent earlobe keloids with a low rate of recurrence and high patient
satisfaction.
PMID- 27506500
TI - Chronic subcutaneous nodules, plaques and ulcers of the hand.
PMID- 27506501
TI - Progressive Nagashima-type palmoplantar keratosis in a Chinese patient with
recurrent c.796C>T mutation in SERPINB7.
PMID- 27506503
TI - A retrospective study of the utility of targeted phototherapy in vitiligo.
AB - BACKGROUND: Targeted phototherapy is a recent advance in the treatment of
vitiligo, involving selective treatment of vitiligo patches with no effect on
surrounding areas. Although it has been in use for a few years, little data is
available regarding its safety and efficacy. AIMS: A retrospective study to
determine efficacy and safety of targeted phototherapy in vitiligo. METHODS: One
hundred and thirty four patients (male: 53, female: 81) who received targeted
phototherapy and completed 11 or more sittings were included. Treatment was given
once a week using the Lumera phototherapy system, a broadband ultraviolet B
source, starting at 150 mJ/spot and after excluding a sunburn reaction, with
increments of 50 mJ every week up to a maximum of 1000 mJ/patch. Chi-square test
for linear trends was used for statistical analysis. RESULTS: The most common
sites involved were the legs and a majority (70.9%) had non-segmental vitiligo.
Response was mild in 78 (58.2%) patients, moderate in 50 (37.3%) and excellent in
6 (4.5%) patients. Response was directly proportional to the number of sittings
with more patients showing moderate and excellent responses with an increase in
the number of sittings. The most common site for an excellent response was the
trunk while the lower limbs were involved in most cases with a moderate or mild
response. Side effects were seen in 27 (20.2%) patients, the commonest being
erythema. LIMITATIONS: This is a retrospective uncontrolled study. Further, the
effects of adjuvant treatment were not assessed. CONCLUSIONS: Targeted
phototherapy is a useful treatment for vitiligo with mild adverse effects, though
response is mild or moderate and appears to be directly proportional to the
number of treatments received.
PMID- 27506502
TI - Paronychia and onychomadesis due to pemphigus vulgaris.
PMID- 27506504
TI - Tinea pseudoimbricata.
PMID- 27506505
TI - A study of the free radical scavenging effects of Piper betle leaf extract in
patients with vitiligo.
AB - BACKGROUND: Vitiligo is an idiopathic skin disease manifested by depigmented
macules. It is characterised by melanocyte destruction, and redox imbalance is
proposed to play a contributory role. AIM: The aim of this study was to analyze
the effects of an ethanolic extract of Piper betle leaves on the generation of
reactive oxygen species in erythrocytes sourced from vitiligo patients. METHODS:
The effect of Piper betle on the generation of reactive oxygen species in
erythrocytes was measured by flow cytometry in patients with active and stable
vitiligo versus healthy controls, using 5-(and-6)-chloromethyl-2'-7'
dichlorodihydrofluorescein diacetate. RESULTS: The generation of reactive oxygen
species in erythrocytes was higher in patients with vitiligo (n = 23) compared to
healthy controls (n = 18). The geometrical mean fluorescence channel was 23.05 +/
2.11 in patients versus 17.77 +/- 1.79 in controls, P = 0.039. The levels of
reactive oxygen species were higher in patients with active vitiligo. Treatment
of erythrocytes with Piper betle in concentrations of 0.5 and 1.0 MUg/ml
significantly decreased the baseline levels of reactive oxygen species by 31.7%
in healthy controls, and 47.6% and 44.3% in patients with active vitiligo,
respectively. Piper betle effectively scavenged hydrogen peroxide, which was
evident by a decrease in the geometrical mean fluorescence channel by 52.4% and
62.9% in healthy controls, and 45.0% and 57.0% in patients with active vitiligo.
LIMITATIONS: The study had a small sample size. Future studies should focus on
evaluation of the antioxidant role of Piper betle at the lesional site.
CONCLUSION: This pilot study indicates that patients with active vitiligo
demonstrate enhanced generation of reactive oxygen species in erythrocytes, which
was significantly reduced following ex vivo treatment with Piper betle.
PMID- 27506506
TI - Familial eyelash trichomegaly: The case of a sister and a brother.
PMID- 27506507
TI - Pagetoid Bowen's disease of vulva: Excellent response to imiquimod.
PMID- 27506508
TI - Current molecular methods for the detection of hepatitis B virus quasispecies.
AB - Chronic HBV infection affects more than 240 million people worldwide and is
associated with a broad range of clinical manifestations including liver
cirrhosis, liver failure and hepatocellular carcinoma. Because of the lack of an
efficient cure for chronic hepatitis B, the main goal of antiviral therapy is the
prevention of liver disease progression coupled with prolonged survival of
patients. Because HBV viral load has been shown to be a crucial determinant of
the progression of liver damage, these goals can be achieved as long as HBV
replication can be suppressed. Unfortunately, long-term therapy with the low-to
moderate genetic barrier drugs, which are still recommended in a majority of
developing countries, are strongly associated with HBV resistance development and
treatment failure. In such cases, the precise and accurate determination of drug
resistant variants in an individual patient before treatment is important for a
proper choice of first-line potent therapy. Nowadays, a number of techniques are
available to study HBV quasispecies evolution. This review describes the
advantages and limitations of various assays detecting drug-resistant HBV
variants. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27506509
TI - Antimicrobial resistance in zoonotic nontyphoidal Salmonella: an alarming trend?
AB - Zoonotic bacteria of the genus Salmonella have acquired various antimicrobial
resistance properties over the years. The corresponding resistance genes are
commonly located on plasmids, transposons, gene cassettes, or variants of the
Salmonella Genomic Islands SGI1 and SGI2. Human infections by nontyphoidal
Salmonella isolates mainly result from ingestion of contaminated food. The two
predominantly found Salmonella enterica subsp. enterica serovars in the USA and
in Europe are S. Enteritidis and S. Typhimurium. Many other nontyphoidal
Salmonella serovars have been implicated in foodborne Salmonella outbreaks.
Summary reports of the antimicrobial susceptibility patterns of nontyphoidal
Salmonella isolates over time suggest a moderate to low level of antimicrobial
resistance and multidrug-resistance. However, serovar-specific analyses showed in
part a steady state, a continuous decline, or a recent increase in resistance to
certain antimicrobial agents. Resistance to critically important antimicrobial
agents, e.g. third-generation cephalosporins and (fluoro)quinolones is part of
many monitoring programmes and the corresponding results confirm that extended
spectrum beta-lactamases are still rarely found in nontyphoidal Salmonella
serovars, whereas resistance to (fluoro)quinolones is prevalent at variable
frequencies among different serovars from humans and animals in different
countries. Although it is likely that nontyphoidal Salmonella isolates from
animals represent a reservoir for resistance determinants, it is mostly unknown
where and when Salmonella isolates acquired resistance properties and which
exchange processes have happened since then.
PMID- 27506510
TI - Small lesion size measured by colposcopy may predict absence of cervical
intraepithelial neoplasia in a large loop excision of the transformation zone
specimen.
AB - OBJECTIVE: To evaluate whether colposcopic measurement of the lesion size at
diagnosis and/or human papillomavirus (HPV) genotyping can predict the absence of
dysplasia in a large loop excision of the transformation zone (LLETZ) specimen in
women treated for squamous intraepithelial lesions/cervical intraepithelial
neoplasia (SIL/CIN). DESIGN: Prospective observational study. SETTING: Tertiary
university hospital. POPULATION: A cohort of 116 women who underwent LLETZ
because of biopsy-proven low-grade SIL/CIN that had persisted for 2 years, or
because of a high-grade SIL/CIN diagnosed in the referral visit and
squamocolumnar junction completely visible (types 1 or 2, according to the
International Federation of Cervical Pathology and Colposcopy, IFCPC). METHODS:
After LLETZ the women were classified by histology into the study group (absence
of SIL/CIN in the surgical specimen, 28/116, 24.1%) and the control group
(SIL/CIN in the LLETZ specimen, 88/116, 75.9%). MAIN OUTCOME MEASURES: The size
of the lesion determined in the diagnostic colposcopy and the HPV genotype were
evaluated in all women. RESULTS: The lesion size was significantly smaller in the
study group (25.7 +/- 37.8 versus 84.5 +/- 81.7 mm2 ; P < 0.001). A lesion size
of <=12 mm2 and HPV types other than 16 or 18 were associated with an absence of
SIL/CIN in the LLETZ specimen (P < 0.001 and P = 0.016, respectively). On
multivariate analysis only a lesion size of <=12 mm2 predicted the absence of
SIL/CIN (odds ratio, OR 10.6; 95% confidence interval, 95% CI 3.6-30.6; P <
0.001). A lesion size of <=12 mm2 had a specificity of 90.9% (95% CI 83.0-95.3%)
and a negative predictive value of 86.0% (95% CI 77.5-91.6%) to predict the
absence of SIL/CIN in the surgical specimen. CONCLUSIONS: Small lesion size in
diagnostic colposcopy could predict the absence of SIL/CIN in the LLETZ specimen.
Colposcopy measurement of lesion size prior to LLETZ may avoid unnecessary
treatment. TWEETABLE ABSTRACT: Small lesion size in colposcopic evaluation might
predict the absence of SIL/CIN in an LLETZ specimen.
PMID- 27506511
TI - Unexpected solvent impact in the crystallinity of
praziquantel/poly(vinylpyrrolidone) formulations. A solubility, DSC and solid
state NMR study.
AB - The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid
dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the
solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The
presence of PVP improves the solubility of PZQ (0.31+/-0.01mg/mL). A maximum of
1.29+/-0.03mg/mL of PZQ in solution was achieved for the 3:1 SD (E/E). The amount
of PZQ in solution depends on the amount of polymer and on the preparation
method. Solid-state NMR (ssNMR) and DSC were used to understand this behavior.
Results show that PMs are a mixture of crystalline PZQ with the polymer, while
SDs show different degrees of drug amorphization depending on the solvent used.
For E/W SDs, PZQ exists in amorphous and crystalline states, with no clear
correlation between the amount of crystalline PZQ and the amount of PVP. For E/E
SDs, formulations with a higher percentage of PZQ are amorphous with the
components miscible in domains larger than 3nm ((1)H ssNMR relaxation
measurements). Albeit its higher saturation solubility, the 3:1 E/E PVP:PZQ
sample has a significant crystalline content, probably due to the water
introduced by the polymer. High PVP content and small crystal size account for
this result.
PMID- 27506512
TI - Controlled drug release from lung-targeted nanocarriers via chemically mediated
shell permeabilisation.
AB - Nanocarriers can aid therapeutic agent administration to the lung, but
controlling drug delivery from these systems after deposition in the airways can
be problematic. The aim of this study was to evaluate if chemically mediated
shell permeabilisation could help manipulate the rate and extent of nanocarrier
drug release. Rifampicin was loaded into lipid shell (loading efficiency 41.0+/
11.4%, size 50nm) and polymer shell nanocarriers (loading efficiency 25.9+/-2.3%,
size 250nm). The drug release at pH 7.4 (lung epithelial pH) and 4.2 (macrophage
endosomal pH) with and without the chemical permeabilisers (Pluronic L62D - lipid
nanocarriers; H(+)- polymer nanocarriers) was then tested. At pH 7.4 the presence
of the permeabilisers increased nanocarrier drug release rate (from 3.2MUg/h to
6.8MUg/h for lipid shell nanocarriers, 2.3MUg/h to 3.4MUg/h for polymer shell
nanocarriers) and drug release extent (from 50% to 80% for lipid shell
nanocarriers, from 45% to 76% for polymer shell nanocarriers). These effects were
accompanied by lipid nanocarrier distension (from 50 to 240nm) and polymer shell
hydrolysis. At pH 4.2 the polymer nanocarriers did not respond to the
permeabiliser, but the lipid nanocarrier maintained a robust drug release
enhancement response and hence they demonstrated that the manipulation of
controlled drug release from lung-targeted nanocarriers was possible through
chemically mediated shell permeabilisation.
PMID- 27506513
TI - Challenges in the first seizure clinic for adult patients with epilepsy.
AB - AIMS: (1) To delineate the challenges in seizure diagnosis in the first seizure
clinic setting for adult patients of a teaching hospital, and (2) quantify the
diagnostic accuracy of the referral source and the yield of routine
investigations, including blood tests, EEGs, and neuroimaging. METHODS: We
retrospectively reviewed medical records of patients referred by the emergency
department to the adult first seizure clinic and seen by the same epilepsy
specialist between June 2007 and June 2011. The diagnostic accuracy in the
emergency department was calculated by comparing with the final diagnosis made by
an epilepsy specialist. RESULTS: In total, 219 patients were referred to the
first seizure clinic. Median age was 45 and 60% of patients were male. From the
cohort, 38 (17%) patients presented with seizure mimickers; the most common were
reflex syncope (74%) and psychogenic non-epileptic seizures (16%). From the
remaining 181 patients presenting with seizures, only 110 (61%) of these patients
were diagnosed with true first seizures, and 71 (39%) patients had evidence of
previous seizures. Nineteen (17%) of true first-ever seizures were provoked. The
most frequent cause of provoked seizures was alcohol and illicit drugs (65%). In
the emergency department, sensitivity and specificity in seizure diagnosis were
0.74 and 0.32, respectively. In our true first seizure patients, the EEG
demonstrated epileptiform discharges in 22 (21%) patients. In the same cohort,
computed tomography and magnetic resonance neuroimaging conferred 16% and 20%
probability of finding a potentially epileptogenic structural abnormality,
respectively. The most common epileptogenic abnormality found on magnetic
resonance neuroimaging was cortical infarct. CONCLUSIONS: The diagnosis and
management of first seizure remains challenging due to the variety of seizure
mimickers and low yield of investigations. Our data highlight the potential
pitfalls and practical challenges in this process, as well as the need for these
patients to be assessed in dedicated first seizure clinics.
PMID- 27506514
TI - Photonic Weyl degeneracies in magnetized plasma.
AB - Weyl particles are elusive relativistic fermionic particles with vanishing mass.
While not having been found as an elementary particle, they are found to emerge
in solid-state materials where three-dimensional bands develop a topologically
protected point-like crossing, a so-called Weyl point. Photonic Weyl points have
been recently realised in three-dimensional photonic crystals with complex
structures. Here we report the presence of a novel type of plasmonic Weyl points
in a naturally existing medium-magnetized plasma, in which Weyl points arise as
crossings between purely longitudinal plasma modes and transverse helical
propagating modes. These photonic Weyl points are right at the critical
transition between a Weyl point with the traditional closed finite equifrequency
surfaces and the newly proposed 'type II' Weyl points with open equifrequency
surfaces. Striking observable features of plasmon Weyl points include a half k
plane chirality manifested in electromagnetic reflection. Our study introduces
Weyl physics into homogeneous photonic media, which could pave way for realizing
new topological photonic devices.
PMID- 27506515
TI - Influence of dentin pretreatment with synthetic hydroxyapatite application on the
bond strength of fiber posts luted with 10-methacryloyloxydecyl dihydrogen
phosphate-containing luting systems.
AB - The aim of this in vitro study was evaluate the effect of application of
synthetic hydroxyapatite on fiber post bond strength to radicular dentine. Forty,
single-root teeth were endodontically treated and an 8 mm post space was
prepared. Specimens were randomly placed in four groups (n = 10 in each) and
treated using the following fiber post luting procedures: group 1, 17% EDTA +
Panavia SA; group 2, 17% EDTA + Teethmate Desensitizer + Panavia SA; group 3, All
Bond Universal + Duo-Link Universal; and group 4, All-Bond Universal + Teethmate
Desensitizer + Duo-Link Universal. Fiber posts were luted in the post space and
light-cured for 120 s using a light-emitting diode (LED) lamp. After 7 d of
storage at 37 degrees C, the teeth were cut into 1-mm-thick slices, which were
subjected to a push-out test until failure using a universal testing machine. Two
specimens per group were prepared for scanning electron microscopy analysis. An
energy-dispersive X-ray spectroscopy detector was used for elemental analysis of
the specimen surface. The results were statistically analyzed using one-way
anova. The fiber post bond strength was statistically significantly increased
after the application of Teethmate Desensitizer to post space walls, either with
a 10-MDP-containing self-adhesive cement or with a universal adhesive. Scanning
electron microscopy and EDAX analysis showed that Teethmate Desensitizer created
a calcium phosphate precipitate over post space dentinal tubules, which
significantly improved the bond strength of the fiber post luted with 10
methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing adhesive systems.
PMID- 27506516
TI - Nasopharyngeal teratoma, congenital diaphragmatic hernia and Dandy-Walker
malformation - a yet uncharacterized syndrome.
AB - An association of congenital diaphragmatic hernia, dandy walker malformation and
nasopharyngeal teratoma is very rare. Here, we report a fourth case with this
association where chromosomal microarray and whole exome sequencing (WES) was
performed to understand the underlying genetic basis. Findings of few variants
especially a novel variation in HIRA provided some insights. An association of
congenital diaphragmatic hernia, dandy walker malformation and nasopharyngeal
teratoma is very rare. Here, we report a fourth case with this association where
chromosomal microarray and whole exome sequencing (WES) was performed to
understand the underlying genetic basis. Findings of few variants especially a
novel variation in HIRA provided some insights.
PMID- 27506517
TI - Electromicrobiology: realities, grand challenges, goals and predictions.
AB - Electromicrobiology is a subdiscipline of microbiology that involves
extracellular electron transfer (EET) to (or from) insoluble electron active
redox compounds located outside the outer membrane of the cell. These
interactions can often be studied using electrochemical techniques which have
provided novel insights into microbial physiology in recent years. The mechanisms
(and variations) of outward EET are well understood for two model systems,
Shewanella and Geobacter, both of which employ multihaem cytochromes to provide
an electron conduit to the cell exterior. In contrast, little is known of the
intricacies of inward EET, even in these model systems. Given the number of labs
now working on EET, it seems likely that most of the mechanistic details will be
understood in a few years for the model systems, and the many applications of
electromicrobiology will continue to move forward. But emerging work, using
electrodes as electron acceptors and donors is providing an abundance of new
types of microbes capable of EET inward and/or outward: microbes that are clearly
different from our known systems. The extent of this very diverse, and perhaps
widely distributed and biogeochemically important ability needs to be determined
to understand the mechanisms, importance, and raison d'etre of EET for microbial
biology.
PMID- 27506518
TI - Promotion of Organic Reactions by Non-Benzenoid Carbocyclic Aromatic Ions.
AB - The first three primary members of the non-benzenoid carbocyclic aromatic ion
family, namely cyclopropenium, cyclopentadienide, and cycloheptatrienium
(tropylium) ions, have planar cyclic structures with (4n+2)pi electrons in fully
conjugated systems. They fulfill Huckel's rule for aromaticity and hence possess
extraordinary stability. Since the historic discovery of tropylium bromide in the
late 19th Century, these non-benzenoid aromatic ions have attracted a lot of
attention because of their unique combination of stability and reactivity. The
charge on the aromatic ions makes them more prone to nucleophilic/electrophilic
reactions than the neutral benzenoid counterparts. Within the last seven years,
there has been a large number of investigations in utilizing aromatic ions to
mediate organic reactions. This Review highlights these recent developments and
discusses the potential of aromatic ions in promoting synthetically useful
organic transformations.
PMID- 27506521
TI - Resumes dans ce numero.
PMID- 27506519
TI - The use of T-DNA insertional mutagenesis to improve cellulase production by the
thermophilic fungus Humicola insolens Y1.
AB - Humicola insolens is an excellent producer of pH-neutral active, thermostable
cellulases that find many industrial applications. In the present study, we
developed an efficient Agrobacterium tumefaciens-mediated transformation system
for H. insolens. We transformed plasmids carrying the promoter of the
glyceraldehyde-3-phosphate dehydrogenase gene of H. insolens driving the
transcription of genes encoding neomycin phosphotransferase, hygromycin B
phosphotransferase, and enhanced green fluorescent protein. We optimized
transformation efficiency to obtain over 300 transformants/10(6) conidia. T-DNA
insertional mutagenesis was employed to generate an H. insolens mutant library,
and we isolated a transformant termed T4 with enhanced cellulase and
hemicellulase activities. The FPase, endoglucanase, cellobiohydrolase, beta
glucosidase, and xylanase activities of T4, measured at the end of fermentation,
were 60%, 440%, 320%, 41%, and 81% higher than those of the wild-type strain,
respectively. We isolated the sequences flanking the T-DNA insertions and thus
identified new genes potentially involved in cellulase and hemicellulase
production. Our results show that it is feasible to use T-DNA insertional
mutagenesis to identify novel candidate genes involved in cellulase production.
This will be valuable when genetic improvement programs seeking to enhance
cellulase production are planned, and will also allow us to gain a better
understanding of the genetics of the thermophilic fungus H. insolens.
PMID- 27506522
TI - Resumenes en esta edicion.
PMID- 27506523
TI - Invasive liver abscess syndrome predisposed by Klebsiella pneumoniae related
prostate abscess in a nondiabetic patient: a case report.
AB - BACKGROUND: Prostate abscess is usually a complication of acute urinary tract
infection. Invasive liver abscess syndrome is characterized with Klebsiella
pneumoniae related multiple organ metastasis. Concomitant pyogenic liver abscess
and prostate abscess have rarely been reported. Recurrent episode of liver
abscess is even rarer. CASE PRESENTATION: We report a 71-year-old male with acute
bacterial prostate abscess and urinary tract infection caused by K. pneumoniae
associated with multiple liver abscess, psoas muscle abscess and osteomyelitis.
Blood culture and urine culture yielded K. pneumoniae, which confirmed the
diagnosis of invasive liver abscess syndrome caused by K. pneumoniae. The patient
was successfully treated with empirical antibiotics for 6 weeks. CONCLUSIONS:
This case emphasizes the importance of timely and accurate diagnosis followed by
appropriate treatment in disseminated K. pneumoniae infection to prevent
significant morbidity and mortality.
PMID- 27506524
TI - Responsiveness and minimal important change for the ProFitMap-neck questionnaire
and the Neck Disability Index in women with neck-shoulder pain.
AB - PURPOSE: The aim was to determine the responsiveness and minimal important change
(MIC) of the questionnaire ProFitMap-neck that measures symptoms and functional
limitations in women with neck pain. The same measurement properties were
determined for Neck Disability Index (NDI) for comparison purposes. METHODS:
Longitudinal data were derived from two randomized controlled trials, including
103 and 120 women with non-specific neck pain, with questionnaire measurements
performed before and after interventions. Sensitivity and specificity to
discriminate between improved and not or little changed participants, based on
categorization of a global rating of change scale (GRCS), were determined for the
ProFitMap-neck indices and NDI by using area under receiver operating
characteristic curves (AUC). Correlations between the GRCS anchor and change
scores of the questionnaires were also used to assess responsiveness. The change
score that showed the highest combination of sensitivity and specificity was set
for MIC. RESULTS: The ProFitMap-neck indices showed similar responsiveness as NDI
with AUC exceeding 0.70 (Range: ProFitMap-neck, 0.74-0.83; NDI, 0.75-0.86). The
MIC in the two samples ranged between 6.6 and 13.6 % for ProFitMap-neck indices
and 5.2 and 6.3 % for NDI. Both questionnaires had significant correlations with
GRCS (Spearman's rho 0.47-0.72). CONCLUSIONS: Validity of change scores was
endorsed for the ProFitMap-neck indices and NDI with adequate ability to
discriminate between improved and not or little changed participants. Values of
minimal important change were presented.
PMID- 27506525
TI - Validation of World Health Organization Assessment Schedule 2.0 in specialized
somatic rehabilitation services in Norway.
AB - PURPOSE: The World Health Organization Disability Assessment Schedule (WHODAS)
2.0 is a generic instrument to assess disability covering six domains. The
purpose of this study was to investigate the potential of the instrument for
monitoring disability in specialized somatic rehabilitation by testing
reliability, construct validity and responsiveness of WHODAS 2.0, Norwegian
version, among patients with various health conditions. METHODS: For taxonomy,
terminology and definitions, the Consensus-based Standards for the Selection of
Health Measurement Instruments were followed. Reproducibility was investigated by
the intra-class correlation coefficient (ICC) in a randomly selected sample.
Internal consistency was assessed by Cronbach's alpha. Construct validity was
evaluated by correlations between WHODAS 2.0 and the Medical Outcomes Study 36
item Short Form, and fit of the hypothesized structure using confirmatory factor
analysis (CFA). Responsiveness was evaluated in another randomly selected sample
by testing a priori formulated hypotheses. RESULTS: Nine hundred seventy patients
were included in the study. Reproducibility and responsiveness were evaluated in
53 and 104 patients, respectively. The ICC for the WHODAS 2.0 domains ranged from
0.63 to 0.84 and was 0.87 for total score. Cronbach's alpha for domains ranged
from 0.75 to 0.94 and was 0.93 for total score. For construct validity, 6 of 12
expected correlations were confirmed and CFA did not achieve satisfactory fit
indices. For responsiveness, 3 of 8 hypotheses were confirmed. CONCLUSION: The
Norwegian version of WHODAS 2.0 showed moderate to satisfactory reliability and
moderate validity in rehabilitation patients. However, the present study
indicated possible limitations in terms of responsiveness.
PMID- 27506527
TI - STORMy Interactions: Gaze and the Modulation of Mimicry in Adults on the Autism
Spectrum.
AB - Mimicry involves unconsciously imitating the actions of others and is a powerful
and ubiquitous behavior in social interactions. There has been a long debate over
whether mimicry is abnormal in people with autism spectrum conditions (ASC) and
what the causes of any differences might be. Wang and Hamilton's (2012) social
top-down response modulation (STORM) model proposed that people with ASC can and
do mimic but, unlike neurotypical participants, fail to modulate their mimicry
according to the social context. This study used an established mimicry paradigm
to test this hypothesis. In neurotypical participants, direct gaze specifically
enhanced congruent hand actions as previously found; in the ASC sample, direct
gaze led to faster reaction times in both congruent and incongruent movements.
This result shows that mimicry is intact in ASC, but is not socially modulated by
gaze, as predicted by STORM.
PMID- 27506526
TI - Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and
Disease: Part II: Mechanistic Models and In Vitro-In Vivo Extrapolation.
AB - It is envisaged that application of mechanistic models will improve prediction of
changes in renal disposition due to drug-drug interactions, genetic polymorphism
in enzymes and transporters and/or renal impairment. However, developing and
validating mechanistic kidney models is challenging due to the number of
processes that may occur (filtration, secretion, reabsorption and metabolism) in
this complex organ. Prediction of human renal drug disposition from preclinical
species may be hampered by species differences in the expression and activity of
drug metabolising enzymes and transporters. A proposed solution is bottom-up
prediction of pharmacokinetic parameters based on in vitro-in vivo extrapolation
(IVIVE), mediated by recent advances in in vitro experimental techniques and
application of relevant scaling factors. This review is a follow-up to the Part I
of the report from the 2015 AAPS Annual Meeting and Exhibition (Orlando, FL; 25th
29th October 2015) which focuses on IVIVE and mechanistic prediction of renal
drug disposition. It describes the various mechanistic kidney models that may be
used to investigate renal drug disposition. Particular attention is given to
efforts that have attempted to incorporate elements of IVIVE. In addition, the
use of mechanistic models in prediction of renal drug-drug interactions and
potential for application in determining suitable adjustment of dose in kidney
disease are discussed. The need for suitable clinical pharmacokinetics data for
the purposes of delineating mechanistic aspects of kidney models in various
scenarios is highlighted.
PMID- 27506528
TI - Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic
neuropathy.
AB - Diabetic neuropathy (DN) is characterized as Hyperglycemia activates thdisturbed
nerve conduction and progressive chronic pain. Inflammatory mediators,
particularly cytokines, have a determinant role in the pathogenesis of
neuropathic pain. The activity of adenosine monophosphate protein kinase (AMPK),
an energy charge sensor with neuroprotective properties, is decreased in
diabetes. It has been reported that activation of AMPK reduces the systemic
inflammation through inhibition of cytokines. In this study, we aimed to
investigate the probable protective effects of AMPK on DN in a rat of diabetes.
DN was induced by injection of streptozotocin (65 mg/kg, i.p.). Motor nerve
conduction velocities (MNCV) of the sciatic nerve, as an electrophysiological
marker for peripheral nerve damage, were measured. Plasma levels of IL-6, TNF
alpha, CRP were assessed as relevant markers for inflammatory response. Also, the
expression of phosphorylated AMPK (p-AMPK) and non-phosphorylated (non-p-AMPK)
was evaluated by western blotting in the dorsal root ganglia. Histopathological
assessment was performed to determine the extent of nerve damage in sciatic
nerve. Our findings showed that activation of AMPK by metformin (300 mg/kg)
significantly increased the MNCV and reduced the levels of inflammatory
cytokines. In addition, we showed that administration of metformin increased the
expression of p-AMPK as well as decline in the level of non p-AMPK. Our results
demonstrated that co-administration of dorsomorphin with metformin reversed the
beneficial effects of metformin. In conclusion, the results of this study
demonstrated that the activation of AMPK signaling pathway in diabetic neuropathy
might be associated with the anti-inflammatory response.
PMID- 27506529
TI - The HB22.7-vcMMAE antibody-drug conjugate has efficacy against non-Hodgkin
lymphoma mouse xenografts with minimal systemic toxicity.
AB - In this study, HB22.7, an anti-CD22 monoclonal antibody, was used for specific,
targeted delivery of monomethyl auristatin E (MMAE) to non-Hodgkin lymphoma
(NHL). MMAE was covalently coupled to HB22.7 through a valine-citrulline peptide
linker (vc). Maleimide-functionalized vcMMAE (mal-vcMMAE) was reacted with thiols
of the partially reduced mAb. Approximately 4 molecules of MMAE were conjugated
to HB22.7 as determined by residual thiol measurement and hydrophobic interaction
chromatography-HPLC (HIC-HPLC). HB22.7-vcMMAE antibody-drug conjugate (ADC)
retained its binding to Ramos NHL cells and also exhibited potent and specific in
vitro cytotoxicity on a panel of B cell NHL cell lines with IC50s of 20-284
ng/ml. HB22.7-vcMMAE also showed potent efficacy in vivo against established NHL
xenografts using the DoHH2 and Granta 519 cell lines. One dose of the ADC induced
complete and persistent response in all DoHH2 xenografts and 90 % of Granta
xenografts. Minimal toxicity was observed. In summary, HB22.7-vcMMAE is an
effective ADC that should be evaluated for clinical translation.
PMID- 27506530
TI - Optical Properties of Silicon Nanowires Fabricated by Environment-Friendly
Chemistry.
AB - Silicon nanowires (SiNWs) were fabricated by metal-assisted chemical etching
(MACE) where hydrofluoric acid (HF), which is typically used in this method, was
changed into ammonium fluoride (NH4F). The structure and optical properties of
the obtained SiNWs were investigated in details. The length of the SiNW arrays is
about 2 MUm for 5 min of etching, and the mean diameter of the SiNWs is between
50 and 200 nm. The formed SiNWs demonstrate a strong decrease of the total
reflectance near 5-15 % in the spectral region lambda < 1 MUm in comparison to
crystalline silicon (c-Si) substrate. The interband photoluminescence (PL) and
Raman scattering intensities increase strongly for SiNWs in comparison with the
corresponding values of the c-Si substrate. These effects can be interpreted as
an increase of the excitation intensity of SiNWs due to the strong light
scattering and the partial light localization in an inhomogeneous optical medium.
Along with the interband PL was also detected the PL of SiNWs in the spectral
region of 500-1100 nm with a maximum at 750 nm, which can be explained by the
radiative recombination of excitons in small Si nanocrystals at nanowire
sidewalls in terms of a quantum confinement model. So SiNWs, which are fabricated
by environment-friendly chemistry, have a great potential for use in photovoltaic
and photonics applications.
PMID- 27506531
TI - Oxidation Resistance of Materials Based on Ti3AlC2 Nanolaminate at 600 degrees C
in Air.
AB - The oxidation behavior of Ti3AlC2-based materials had been investigated at 600
degrees C in static air for 1000 h. It was shown that the intense increase of
weight gain per unit surface area for sintered material with porosity of 22 %
attributed to oxidation of the outer surface of the specimen and surfaces of
pores in the bulk material. The oxidation kinetics of the hot-pressed Ti3AlC2
based material with 1 % porosity remarkably increased for the first 15 h and then
slowly decreased. The weight gain per unit surface area for this material was 1.0
mg/cm(2) after exposition for 1000 h. The intense initial oxidation of Ti3AlC2
based materials can be eliminated by pre-oxidation treatment at 1200 degrees C
in air for 2 h. As a result, the weight gain per unit surface area for the pre
oxidized material did not exceed 0.11 mg/cm(2) after 1000 h of exposition at 600
degrees C in air. It was demonstrated that the oxidation resistance of Ti3AlC2
based materials can be significantly improved by niobium addition.
PMID- 27506533
TI - Localization of the Reflection Sources of Stimulus-Frequency Otoacoustic
Emissions.
AB - The generation of stimulus-frequency otoacoustic emission (SFOAE) residuals in
humans is analyzed both theoretically and experimentally to investigate the
relation between the frequency difference between the probe and the suppressor
tone and the localization of the residual source. Experimental measurements of
the SFOAE residual were performed using suppressors of increasing frequency to
separate the otoacoustic response from the probe stimulus. From the response to
the probe alone, the SFOAE response was also estimated, using spectral smoothing,
and compared with the residuals obtained for different frequency suppressors. A
nonlinear delayed-stiffness active cochlear model was used to compute the spatial
distribution of the residual sources according to a recent model of the local
reflectivity from roughness, as a function of the suppressor frequency. The
simulations clarified the role of high-frequency suppressors, showing that in
humans, with increasing suppressor frequency, the generation region of the
residual is only slightly basally shifted with respect to the case of a near
frequency suppressor, near the basal edge of the peak of the resonant basilar
membrane response. As a consequence, the hierarchy among different-delay
components correspondingly changes, gradually favoring short-delay components,
with increasing suppressor frequency. Good agreement between the experimental and
theoretical dependence of the level of otoacoustic components of different delay
on the frequency shift between probe and suppressor confirms the validity of this
interpretation.
PMID- 27506532
TI - Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart
failure.
AB - Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is
often associated with arrhythmias and sudden cardiac death if not controlled. The
majority of DCM is of unknown etiology. Protein sialylation is altered in human
DCM, with responsible mechanisms not yet described. Here we sought to investigate
the impact of clinically relevant changes in sialylation on cardiac function
using a novel model for altered glycoprotein sialylation that leads to DCM and to
chronic stress-induced heart failure (HF), deletion of the sialyltransferase,
ST3Gal4. We previously reported that 12- to 20-week-old ST3Gal4 (-/-) mice showed
aberrant cardiac voltage-gated ion channel sialylation and gating that contribute
to a pro-arrhythmogenic phenotype. Here, echocardiography supported by histology
revealed modest dilated and thinner-walled left ventricles without increased
fibrosis in ST3Gal4 (-/-) mice starting at 1 year of age. Cardiac calcineurin
expression in younger (16-20 weeks old) ST3Gal4 (-/-) hearts was significantly
reduced compared to WT. Transverse aortic constriction (TAC) was used as a
chronic stressor on the younger mice to determine whether the ability to
compensate against a pathologic insult is compromised in the ST3Gal4 (-/-) heart,
as suggested by previous reports describing the functional implications of
reduced cardiac calcineurin levels. TAC'd ST3Gal4 (-/-) mice presented with
significantly reduced systolic function and ventricular dilation that
deteriorated into congestive HF within 6 weeks post-surgery, while constricted WT
hearts remained well-adapted throughout (ejection fraction, ST3Gal4 (-/-) = 34 +/
5.2 %; WT = 53.8 +/- 7.4 %; p < 0.05). Thus, a novel, sialo-dependent model for
DCM/HF is described in which clinically relevant reduced sialylation results in
increased arrhythmogenicity and reduced cardiac calcineurin levels that precede
cardiomyopathy and TAC-induced HF, suggesting a causal link among aberrant
sialylation, chronic arrhythmia, reduced calcineurin levels, DCM in the absence
of a pathologic stimulus, and stress-induced HF.
PMID- 27506534
TI - Genetics and mapping of seedling resistance to Ug99 stem rust in winter wheat
cultivar Triumph 64 and differentiation of SrTmp, SrCad, and Sr42.
AB - KEY MESSAGE: Resistance to Ug99 stem rust in Triumph 64 was conferred by SrTmp on
chromosome arm 6DS and was mapped to the same position as SrCad and Sr42 ,
however, the three genes show functional differences. Stem rust, caused by
Puccinia graminis f. sp. tritici (Pgt), is an important disease of wheat that can
be controlled by effective stem rust resistance (Sr) genes. The emergence of
virulent Pgt races in Africa, namely Ug99 and its variants, has stimulated the
search for new Sr genes and genetic characterization of known sources of
resistance. Triumph 64 is a winter wheat cultivar that carries gene SrTmp, which
confers resistance to Ug99. The goals of this study were to genetically map SrTmp
and examine its relationship with other Sr genes occupying a similar chromosome
location. A doubled haploid (DH) population from the cross LMPG-6S/Triumph 64 was
inoculated with Ug99 at the seedling stage. A single gene conditioning resistance
to Ug99 segregated in the population. Genetic mapping with SSR markers placed
SrTmp on chromosome arm 6DS in a region similar to SrCad and Sr42. SNP markers
developed for SrCad were used to further map SrTmp and were also added to a
genetic map of Sr42 using a DH population (LMPG-6S/Norin 40). Three SNP markers
that co-segregated with SrTmp also co-segregated with SrCad and Sr42. The SNP
markers showed no difference in the map locations of SrTmp, SrCad, and Sr42.
Multi-race testing with DH lines from the Triumph 64 and Norin 40 populations and
a recombinant inbred-line population from the cross LMPG-6S/AC Cadillac showed
that SrTmp, SrCad, and Sr42 confer different spectra of resistance. Markers
closely linked to SrTmp are suitable for marker-assisted breeding and germplasm
development.
PMID- 27506535
TI - Falcatimonas natans gen. nov., sp. nov., a strictly anaerobic, amino-acid
decomposing bacterium isolated from a methanogenic reactor of cattle waste.
AB - A strictly anaerobic bacterial strain (WN011T) was isolated from a methanogenic
reactor treating waste from cattle farms. Cells of the strain were Gram-stain
negative curved rods with a polar flagellum. Spores were not produced. The
optimum temperature for growth was 35-37 degrees C and the optimum pH was 6.7.
The strain did not utilize carbohydrates as growth substrates. The strain grew in
PY medium and produced acetate, butyrate, isovalerate and H2 as well as
propionate and isobutyrate as minor products. Amino acids (l-isoleucine, l
leucine, l-lysine, l-serine, l-threonine and l-valine) added to PY medium
enhanced growth of the strain and increased the amounts of fermentation products.
Oxidase, catalase and nitrate-reducing activities were negative. Hydrogen sulfide
was produced. The genomic DNA G+C content was 38.8 mol%. Compounds related to iso
C15 : 0 (fatty acid, dimethylacetal and aldehyde) were detected as predominant
components by the cellular fatty acids analysis. The diagnostic diamino acid of
the cell-wall peptidoglycan was meso-diaminopimelic acid. On the basis of 16S
rRNA gene sequences, three clones from wastewater were very closely related to
strain WN011T (up to 99.9 % sequence similarity). The most closely related
described species were those in cluster XIVa of the class Clostridia such as
Ruminococcus gauvreauii (93.8 % 16S rRNA gene sequence similarity), Clostridium
fimetarium (93.5 %) and Clostridium bolteae(93.5 %). Based on the distinct
differences in phylogenetic and phenotypic characteristics of strain WN011T from
those of related species, it is concluded that strain WN011T represents a novel
species of a new genus in the family Lachnospiraceae, for which the name
Falcatimonas natans gen. nov., sp. nov. is proposed. The type strain of the type
species is WN011T (=JCM 16476T=DSM 22923T).
PMID- 27506536
TI - An evaluation of the experiences of guide dog owners visiting Scottish veterinary
practices.
AB - Guide dogs and their owners will visit a veterinary practice at least twice a
year. The aim of this study was to evaluate what guide dog owners thought about
these visits, in order to identify areas of good practice which could be
incorporated into the undergraduate curriculum. Nine guide dog owners volunteered
to take part in the study and were interviewed by the primary researcher.
Thematic analysis was carried out and several themes were identified: good
experiences were highlighted where staff had an understanding of visual
impairment and the work of a guide dog; the importance of good communication
skills involving the owner in the consultation; the need for veterinary
professionals to understand the bond between an owner and guide dog; how
medication and information could be provided in a user-friendly format for
someone affected by a visual impairment and concerns about costs and decision
making for veterinary treatment. This work highlights the importance for
veterinary staff to talk to, empathise with and understand the individual
circumstances of their clients and identifies areas that should be included in
veterinary education to better prepare students for the workplace.
PMID- 27506537
TI - What Are the Top 10 Research Questions in the Treatment of Inflammatory Bowel
Disease? A Priority Setting Partnership with the James Lind Alliance.
AB - BACKGROUND AND AIMS: Many uncertainties remain regarding optimal therapies and
strategies for the treatment of inflammatory bowel disease. Setting research
priorities addressing therapies requires a partnership between health care
professionals, patients and organisations supporting patients. We aimed to use
the structure of the James Lind Alliance Priority Setting Partnership, which has
been used in other disease areas, to identify and prioritise unanswered questions
about treatments for inflammatory bowel disease. METHODS: The James Lind Priority
Setting Partnership uses methods agreed and adopted in other disease areas to
work with patients and clinicians: to identify uncertainties about treatments; to
agree by consensus a prioritised list of uncertainties for research; then to
translate these uncertainties into research questions which are amenable to
hypothesis testing; and finally to take results to research commissioning bodies
to be considered for funding. RESULTS: A total of 1636 uncertainties were
collected in the initial survey from 531 respondents, which included 22% health
care professionals and 78% patients and carers. Using the rigorously applied
processes of the priority setting partnership, this list was distilled down to
the top 10 research priorities for inflammatory bowel disease. The top priorities
were: identifying treatment strategies to optimise efficacy, safety and cost
effectiveness; and stratifying patients with regard to their disease course and
treatment response. Diet and symptom control [pain, incontinence and fatigue]
were also topics which were prioritised. CONCLUSIONS: A partnership involving
multidisciplinary clinicians, patients and organisations supporting patients has
identified the top 10 research priorities in the treatment of patients with
inflammatory bowel disease.
PMID- 27506538
TI - Epigenetic modulation on cat-cow interspecies somatic cell nuclear transfer
embryos by treatment with trichostatin A.
AB - This study aimed to determine the acetylation at lysine 9/18/23 of histone H3
(H3K9ac/H3K18ac/H3K23ac; H3K9/18/23 ac) and the di-methylation at lysine 9 of
histone H3 (H3K9me2) during early embryogenesis among trichostatin A (TSA)
treated interspecies somatic cell nuclear transfer (iSCNT) cat-cow (TSA-iSCNT)
embryos, TSA-untreated iSCNT cat-cow control (control) embryos and bovine in
vitro fertilization (IVF) embryos, because TSA-iSCNT embryos can develop to
blastocysts. Compared to the control embryos, higher expressions of H3K9/18/23 ac
were observed in TSA-iSCNT embryos and IVF embryos at most following stages (2 h
post-fusion / post-insemination (PF/PI) to eight-cell stage). At 6 h PF/PI the
expression of H3K9/23 ac in TSA-iSCNT embryos and IVF embryos were lower than
those in control embryos, and the expression of H3K18ac was no difference among
the three groups. The expression of H3K9/23 ac increased in TSA-iSCNT embryos and
IVF embryos at pronuclear (PN) stages. The expression of H3K9me2 in TSA-iSCNT
embryos resembled that of IVF embryos at 2 h PF/PI to PN stages, and these
expression levels were greater than those of control embryos. These results
suggest that treatment of iSCNT embryos with TSA modifies the patterns of histone
modification at certain lysine residues in a manner that is comparable with that
seen in IVF during early embryogenesis.
PMID- 27506539
TI - Community perceptions of health and rodent-borne diseases along the Inter-Oceanic
Highway in Madre de Dios, Peru.
AB - BACKGROUND: Madre de Dios is located in the southeastern Amazonian region of
Peru. Rodents have been estimated to be the reservoirs for up to 50 % of emerging
zoonotic pathogens, including a host of viruses, bacteria, and parasites. As part
of a larger study involving both human and animal research, this study serves to
obtain a broader understanding of the key challenges and concerns related to
health and rodent-borne illnesses from the perspective of the people living in
these communities. METHODS: We used a mixed methods approach, which comprised of
12 focus group discussions, 34 key informant interviews and the application of a
survey (n = 522) in four communities along the Inter-Oceanic Highway (IOH) in
Madre de Dios, Peru over a two-year period. RESULTS: Although 90 % of survey
respondents answered that rodents can transmit diseases and had seen rodents in
their homes and immediate surroundings, most could not name specific rodent-borne
diseases and, when probed, described rodents as pests or nuisance animals, but
were not concerned about acquiring illnesses from them. Key informant interview
data suggests that there has been a perceived increase in the amount of rodents
in the communities since the construction of the IOH, however this potential
increase was not coupled with increased knowledge about diseases or perceived
risks among these key informants. Health providers also mentioned a lack of
diagnostic tools specific for rodent-borne illnesses. This may be related to the
fact that although a common rodent-borne disease like leptospirosis is frequently
detected in the region, it is not routinely and readily diagnosed, therefore the
real burden of the disease and exposure risk can be underestimated. If rodent
borne diseases are not on the radar of health professionals, they may not
consider presumptive treatment, which could result in unnecessary morbidity and
mortality. CONCLUSION: Awareness of rodent-borne diseases is still lacking in the
area, even among health care professionals within the communities, despite the
known burden of diseases like leptospirosis. We expect to report further findings
as we obtain more information from all the study components.
PMID- 27506540
TI - The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T
cell therapies.
AB - The treatment of multiple myeloma has evolved significantly over the last decades
from primarily alkylator-based chemotherapeutic agents with minimal efficacy to
the introduction of more effective agents including immune modulators and
proteasome inhibitors, which have changed the landscape of therapy for this
disease. We are now entering a new era that will increasingly integrate
immunotherapy into standard treatment. This review discusses the current immune
based strategies currently approved, as well as various immune approaches being
actively investigated including monoclonal antibodies, checkpoint inhibitors,
vaccines, and adoptive T-cell therapies.
PMID- 27506541
TI - Control of GVHD by regulatory T cells depends on TNF produced by T cells and
TNFR2 expressed by regulatory T cells.
AB - Therapeutic CD4(+)Foxp3(+) natural regulatory T cells (Tregs) can control
experimental graft-versus-host disease (GVHD) after allogeneic hematopoietic stem
cell transplantation (allo-HCT) by suppressing conventional T cells (Tconvs).
Treg-based therapies are currently tested in clinical trials with promising
preliminary results in allo-HCT. Here, we hypothesized that as Tregs are capable
of modulating Tconv response, it is likely that the inflammatory environment and
particularly donor T cells are also capable of influencing Treg function. Indeed,
previous findings in autoimmune diabetes revealed a feedback mechanism that
renders Tconvs able to stimulate Tregs by a mechanism that was partially
dependent on tumor necrosis factor (TNF). We tested this phenomenon during
alloimmune response in our previously described model of GVHD protection using
antigen specific Tregs. Using different experimental approaches, we observed that
control of GVHD by Tregs was fully abolished by blocking TNF receptor type 2
(TNFR2) or by using TNF-deficient donor T cells or TNFR2-deficient Tregs. Thus,
our results show that Tconvs exert a powerful modulatory activity on therapeutic
Tregs and clearly demonstrate that the sole defect of TNF production by donor T
cells was sufficient to completely abolish the Treg suppressive effect in GVHD.
Importantly, our findings expand the understanding of one of the central
components of Treg action, the inflammatory context, and support that targeting
TNF/TNFR2 interaction represents an opportunity to efficiently modulate
alloreactivity in allo-HCT to either exacerbate it for a powerful antileukemic
effect or reduce it to control GVHD.
PMID- 27506543
TI - Tadalafil Treatment Delays the Onset of Cardiomyopathy in Dystrophin-Deficient
Hearts.
AB - BACKGROUND: Cardiomyopathy is a leading cause of mortality among Duchenne
muscular dystrophy patients and lacks effective therapies. Phosphodiesterase type
5 is implicated in dystrophic pathology, and the phosphodiesterase type 5
inhibitor tadalafil has recently been studied in a clinical trial for Duchenne
muscular dystrophy. METHODS AND RESULTS: Tadalafil was evaluated for the
prevention of cardiomyopathy in the mdx mouse and golden retriever muscular
dystrophy dog models of Duchenne muscular dystrophy. Tadalafil blunted the
adrenergic response in mdx hearts during a 30-minute dobutamine challenge, which
coincided with cardioprotective signaling, reduced induction of MU-calpain
levels, and decreased sarcomeric protein proteolysis. Dogs with golden retriever
muscular dystrophy began daily tadalafil treatment prior to detectable
cardiomyopathy and demonstrated preserved cardiac function, as assessed by
echocardiography and magnetic resonance imaging at ages 18, 21, and 25 months.
Tadalafil treatment improved golden retriever muscular dystrophy
histopathological features, decreased levels of the cation channel TRPC6,
increased total threonine phosphorylation status of TRPC6, decreased m-calpain
levels and indicators of calpain target proteolysis, and elevated levels of
utrophin. In addition, we showed that Duchenne muscular dystrophy patient
myocardium exhibited increased TRPC6, m-calpain, and calpain cleavage products
compared with control human myocardium. CONCLUSIONS: Prophylactic use of
tadalafil delays the onset of dystrophic cardiomyopathy, which is likely
attributed to modulation of TRPC6 levels and permeability and inhibition of
protease content and activity. Consequently, phosphodiesterase type 5 inhibition
is a candidate therapy for slowing the development of cardiomyopathy in Duchenne
muscular dystrophy patients.
PMID- 27506542
TI - Socioeconomic status as a moderator between frailty and mortality at old ages.
AB - BACKGROUND: Despite the well-established power of frailty to predict mortality,
and the known associations of socioeconomic status (SES) with mortality, it is
largely unknown whether the linkage between frailty and mortality varies across
different SES groups. This study aims to investigate whether SES moderates the
association between frailty and mortality. METHODS: We relied on the 2008/2009
and 2011/2012 waves of the Chinese Longitudinal Healthy Longevity Survey, a
nationwide sample of 13,731 adults aged 65 or older in China. Frailty was
constructed using a cumulative index of 38 items (with 39 deficits) reflecting
different dimensions of health; the index or the proportion of deficits ranges
from 0 to 1, with greater scores indicating poorer health condition. SES was
measured by a socioeconomic vulnerability index (SEVI) also from a similar
cumulative approach consisting of 6 deficits; the proportion of deficits ranges
from 0 to 1 with higher scores indicating lower SES. Eight Weibull hazard
regression models were performed to examine how SES moderates the linkage between
frailty and mortality. RESULTS: We found that a one percentage point increase in
the frailty index was associated with an increased hazard ratio (HR) by 2.7 % (HR
= 1.027, 95 % CI: 1.025-1.027); a one percentage point increase in SEVI score was
associated with an increased hazard ratio by 0.6 % (HR = 1.006, 95 % CI: 1.004
1.008) controlling for demographics. When interactions between SEVI and frailty
index were modeled, the increased mortality risk associated with frailty was
weaker among people with lower SES than among people with higher SES (HR = 0.983,
95 % CI: 0.967-0.992). However, the moderating role of SES was diminished when
interactions between SES and age and between frailty and age were modeled. With
increasing age, the increased mortality risks associated with frailty and
socioeconomic vulnerability weakened. CONCLUSIONS: Frailty was a stronger
predictor of mortality among individuals with higher SES than those with lower
SES. The increased mortality risks associated with socioeconomic vulnerability
and frailty weakened with age. Public health programs aimed at improving SES and
promoting healthy longevity should start early in old age, or even earlier, and
target poor and frail older adults for maximum impact.
PMID- 27506544
TI - In-Hospital Vital Status and Heart Transplants After Intervention for Congenital
Heart Disease in the Pediatric Cardiac Care Consortium: Completeness of
Ascertainment Using the National Death Index and United Network for Organ Sharing
Datasets.
AB - BACKGROUND: The long-term outcomes of patients undergoing interventions for
congenital heart disease (CHD) remain largely unknown. We linked the Pediatric
Cardiac Care Consortium (PCCC) with the National Death Index (NDI) and the United
Network for Organ Sharing Dataset (UNOS) registries to study mortality and
transplant occurring up to 32 years postintervention. The objective of the
current analysis was to determine the sensitivity of this linkage in identifying
patients who are known to have died or undergone heart transplant. METHODS AND
RESULTS: We used direct identifiers from 59 324 subjects registered in the PCCC
between 1982 and 2003 to test for completeness of case ascertainment of subjects
with known vital and heart transplant status by linkage with the NDI and UNOS
registries. Of the 4612 in-hospital deaths, 3873 were identified by the NDI as
"true" matches for a sensitivity of 84.0% (95% CI, 82.9-85.0). There was no
difference in sensitivity across 25 congenital cardiovascular conditions after
adjustment for age, sex, race, presence of first name, death year, and residence
at death. Of 455 known heart transplants in the PCCC, there were 408 matches in
the UNOS registry, for a sensitivity of 89.7% (95% CI, 86.9-92.3). An additional
4851 deaths and 363 transplants that occurred outside the PCCC were identified
through 2014. CONCLUSIONS: The linkage of the PCCC with the NDI and UNOS national
registries is feasible with a satisfactory sensitivity. This linkage provides a
conservative estimate of the long-term death and heart transplant events in this
cohort.
PMID- 27506545
TI - High resolution metabolomics to discriminate compounds in serum of male lung
cancer patients in South Korea.
AB - BACKGROUND: The cancer death rate escalated during 20th century. In South Korea,
lung cancer is expected to contribute 12,736 deaths in men, the highest amount
among all cancers. Several risk factors may increase the chance to acquiring lung
cancer, with mostly related to exogenous compounds found in cigarette smoke and
synthetic manufacturing materials. As the mortality rate of lung cancer
increases, deeper understanding is necessary to explore risk factors that may
lead to this malignancy. In this regard, this study aims to apply high resolution
metabolomics (HRM) using LC-MS to detect significant compounds that might
contribute in inducing lung cancer and find the correlation of these compounds to
the subjects' smoking habit. METHODS: The comparison was made between healthy
control and lung cancer groups for metabolic differences. Further analyses to
determine if these differences are related to tobacco-induced lung cancer (past
smoker control vs. past-smoker lung cancer patients (LCPs) and non-smoker control
vs. current-smoker LCPs) were selected. The univariate analysis was performed,
including a false discovery rate (FDR) of q = 0.05, to determine the significant
metabolites between the analyses. Hierarchical clustering analysis (HCA) was done
to discriminate metabolites between the control and case subjects. Selected
compounds based on significant m/z features of human serum then experienced MS/MS
examination, showing that for many m/z, the patterns of ion dissociation matched
with standards. Then, the significant metabolites were identified using Metlin
database and features were mapped on the human metabolic pathway mapping tool of
the Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Using metabolomics
wide association studies, metabolic changes were observed among control group and
lung cancer patients. Bisphenol A (211.11, [M + H-H2O](+)), retinol (287.23, [M +
H](+)) and L-proline (116.07, [M + H](+)) were among the significant compounds
found to have contributed in the discrimination between these groups, suggesting
that these compounds might be related in the development of lung cancer. Retinol
has been seen to have a correlation with smoking while both bisphenol A and L
proline were found to be unrelated. CONCLUSIONS: Two potential biomarkers,
retinol and L-proline, were identified and these findings may create
opportunities for the development of new lung cancer diagnostic tools.
PMID- 27506546
TI - Expression of aryl hydrocarbon receptor in rat brain lesions following traumatic
brain injury.
AB - BACKGROUND: Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription
factor with multiple functions operating in a variety of organs, including the
brain. Recent studies have revealed that AhR played a functional role in
traumatic injuries. This paper aims to study the expression of AhR during the
early phase following a traumatic brain injury (TBI) in rat brains by
immunohistochemistry. METHODS: Weight-drop induced TBI was performed in rats. The
expression of AhR in brain of TBI rats were examined by immunohistochemistry.
RESULTS: Neuron expression of AhR in the rat brains of experiment group had been
upregulated since day 3 in lesional hemisphere compared to that of the control
group and mainly located in the cytoplasm, indicating an inactivated state.
Interestingly, the accumulation of AhR(+) non-neuron cells became significant as
early as 18 h after injury, which had kept increasing until 24 h post injury and
then decreased slowly. For AhR(+) non-neuron cells, the AhR mainly located in
cell nucleus, indicating a reactive status. Furthermore, double staining showed
that most AhR(+) non-neuron cells co-localized with W3/13, a marker for T
lymphocytes, but not with ED-1 (for activated microglia/macrophages) or GFAP (for
activated astrocytes), suggesting that most AhR(+) non-neuron cells were T
lymphocytes. CONCLUSION: This is the first study concerning AhR expression in
brains following TBI, and our data demonstrated that AhR was upregulated and
activated in T lymphocytes following TBI. More research is needed to make a more
conclusive conclusion.
PMID- 27506547
TI - Understanding clinical prediction models as 'innovations': a mixed methods study
in UK family practice.
AB - BACKGROUND: Well-designed clinical prediction models (CPMs) often out-perform
clinicians at estimating probabilities of clinical outcomes, though their
adoption by family physicians is variable. How family physicians interact with
CPMs is poorly understood, therefore a better understanding and framing within a
context-sensitive theoretical framework may improve CPM development and
implementation. The aim of this study was to investigate why family physicians do
or do not use CPMs, interpreting these findings within a theoretical framework to
provide recommendations for the development and implementation of future CPMs.
METHODS: Mixed methods study in North West England that comprised an online
survey and focus groups. RESULTS: One hundred thirty eight respondents completed
the survey, which found the main perceived advantages to using CPMs were that
they guided appropriate treatment (weighted rank [r] = 299; maximum r = 414
throughout), justified treatment decisions (r = 217), and incorporated a large
body of evidence (r = 156). The most commonly reported barriers to using CPMs
were lack of time (r = 163), irrelevance to some patients (r = 161), and poor
integration with electronic health records (r = 147). Eighteen clinicians
participated in two focus groups (i.e. nine in each), which revealed 13
interdependent themes affecting CPM use under three overarching domains:
clinician factors, CPM factors and contextual factors. Themes were
interdependent, indicating the tensions family physicians experience in providing
evidence-based care for individual patients. CONCLUSIONS: The survey and focus
groups showed that CPMs were valued when they supported clinical decision making
and were robust. Barriers to their use related to their being time-consuming,
difficult to use and not always adding value. Therefore, to be successful, CPMs
should offer a relative advantage to current working, be easy to implement, be
supported by training, policy and guidelines, and fit within the organisational
culture.
PMID- 27506548
TI - Transcriptome profiling of the rumen epithelium of beef cattle differing in
residual feed intake.
AB - BACKGROUND: Feed efficient cattle consume less feed and produce less
environmental waste than inefficient cattle. Many factors are known to contribute
to differences in feed efficiency, however the underlying molecular mechanisms
are largely unknown. Our study aimed to understand how host gene expression in
the rumen epithelium contributes to differences in residual feed intake (RFI), a
measure of feed efficiency, using a transcriptome profiling based approach.
RESULTS: The rumen epithelial transcriptome from highly efficient (low (L-) RFI,
n = 9) and inefficient (high (H-) RFI, n = 9) Hereford x Angus steers was
obtained using RNA-sequencing. There were 122 genes differentially expressed
between the rumen epithelial tissues of L- and H- RFI steers (p < 0.05) with 85
up-regulated and 37 down-regulated in L-RFI steers. Functional analysis of up
regulated genes revealed their involvement in acetylation, remodeling of adherens
junctions, cytoskeletal dynamics, cell migration, and cell turnover.
Additionally, a weighted gene co-expression network analysis (WGCNA) identified a
significant gene module containing 764 genes that was negatively correlated with
RFI (r = -0.5, p = 0.03). Functional analysis revealed significant enrichment of
genes involved in modulation of intercellular adhesion through adherens
junctions, protein and cell turnover, and cytoskeletal organization that suggest
possible increased tissue morphogenesis in the L-RFI steers. Additionally, the L
RFI epithelium had increased expression of genes involved with the mitochondrion,
acetylation, and energy generating pathways such as glycolysis, tricarboxylic
acid cycle, and oxidative phosphorylation. Further qPCR analysis of steers with
different RFI (L-RFI, n = 35; M-RFI, n = 34; H-RFI, n = 35) revealed that the
relative mitochondrial genome copy number per cell of the epithelium was
positively correlated with RFI (r = 0.21, p = 0.03). CONCLUSIONS: Our results
suggest that the rumen epithelium of L-RFI (efficient) steers may have increased
tissue morphogenesis that possibly increases paracellular permeability for the
absorption of nutrients and increased energy production to support the energetic
demands of increased tissue morphogenesis compared to those of H-RFI
(inefficient) animals. Greater expression of mitochondrial genes and lower
relative mitochondrial genome copy numbers suggest a greater rate of
transcription in the rumen epithelial mitochondria of L-RFI steers. Understanding
how host gene expression profiles are associated with RFI could potentially lead
to identification of mechanisms behind this trait, which are vital to develop
strategies for the improvement of cattle feed efficiency.
PMID- 27506550
TI - Introduction to the Special Series on Fraction Learning.
PMID- 27506549
TI - Prevention of mother-to-child transmission of hepatitis B virus: a phase III,
placebo-controlled, double-blind, randomized clinical trial to assess the
efficacy and safety of a short course of tenofovir disoproxil fumarate in women
with hepatitis B virus e-antigen.
AB - BACKGROUND: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis
and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV.
The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be
about 12 % when mothers have a high hepatitis B viral load, even if infants
receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate
the hepatitis B vaccine series at birth. We designed a study to assess the
efficacy and safety of a short course of maternal tenofovir disoproxil fumarate
(TDF) among women with a marker of high viral load for the prevention of MTCT of
HBV. METHODS: The study is a phase III, multicenter (17 sites in Thailand),
placebo-controlled, double-blind, randomized 1:1, two-arm clinical trial of TDF
300 mg once daily versus placebo among pregnant women from 28 weeks' gestation
through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B
(HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and
6 months. Participant women at study entry must be age >=18 years, hepatitis B
surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine
aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre
entry), negative hepatitis C serology, creatinine clearance >50 mL/min, and no
history of anti-HBV antiviral treatment. The target sample size of 328
mother/infant pairs assumed 156 evaluable cases per arm to detect a >=9 %
difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm)
with 90 % power. Mothers and infants are followed until 12 months after delivery.
The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV
DNA at six months of age. Secondary endpoints are maternal and infant adverse
events, acute exacerbations of maternal hepatitis B disease (ALT >300 IU/L,
defined as a "flare") following discontinuation of study treatment, infant HBV
infection status and growth up to 12 months of age. DISCUSSION: The results of
this randomized trial will clarify the efficacy and safety of a short course of
antiviral treatment to prevent mother-to-child transmission of HBV and inform
international guidelines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier
NCT01745822 .
PMID- 27506551
TI - Delaware Longitudinal Study of Fraction Learning: Implications for Helping
Children With Mathematics Difficulties.
AB - The goal of the present article is to synthesize findings to date from the
Delaware Longitudinal Study of Fraction Learning. The study followed a large
cohort of children ( N = 536) between Grades 3 and 6. The findings showed that
many students, especially those with diagnosed learning disabilities, made
minimal growth in fraction knowledge and that some showed only a basic grasp of
the meaning of a fraction even after several years of instruction. Children with
low growth in fraction knowledge during the intermediate grades were much more
likely to fail to meet state standards on a broad mathematics measure at the end
of Grade 6. Although a range of general and mathematics-specific competencies
predicted fraction outcomes, the ability to estimate numerical magnitudes on a
number line was a uniquely important marker of fraction success. Many children
with mathematics difficulties have deep-seated problems related to whole number
magnitude representations that are complicated by the introduction of fractions
into the curriculum. Implications for helping students with mathematics
difficulties are discussed.
PMID- 27506552
TI - Fraction Sense: Foundational Understandings.
AB - The intent of this commentary is to identify elements of fraction sense and note
how the research studies provided in this special issue, in related but somewhat
different ways, validate the importance of such understandings. Proficiency with
fractions serves as a prerequisite for student success in higher level
mathematics, as well as serving as a gateway to many occupations and varied
contexts beyond the mathematics classroom. Fraction sense is developed through
instructional opportunities involving fraction equivalence and magnitude,
comparing and ordering fractions, using fraction benchmarks, and computational
estimation. Such foundations are then extended to operations involving fractions
and decimals and applications involving proportional reasoning. These components
of fraction sense are all addressed in the studies provided in this issue, with
particular consideration devoted to the significant importance of the use of the
number line as a central representational tool for conceptually understanding
fraction magnitude.
PMID- 27506555
TI - Myocardial dysfunction in diabetes: Another epidemic?
PMID- 27506554
TI - Matrix Metalloproteinase-8 Augments Bacterial Clearance in a Juvenile Sepsis
Model.
AB - Genetic ablation or pharmacologic inhibition of matrix metalloproteinase-8 (MMP8)
improves survival in an adult murine sepsis model. Because developmental age
influences the host inflammatory response, we hypothesized that developmental age
influences the role of MMP8 in sepsis. First, we compared sepsis survival between
wild type (WT, C57BL/6) and MMP8 null juvenile-aged mice (12-14 days) after
intraperitoneal injection of a standardized cecal slurry. Second, peritoneal
lavages collected at 6 and 18 hours after cecal slurry injection were analyzed
for bacterial burden, leukocyte subsets, and inflammatory cytokines. Third,
juvenile WT mice were pretreated with an MMP8 inhibitor prior to cecal slurry
injection; analysis of their bacterial burden was compared to vehicle-injected
animals. Fourth, the phagocytic capacity of WT and MMP8 null peritoneal
macrophages was compared. Finally, peritoneal neutrophil extracellular traps
(NETs) were compared using immunofluorescent imaging and quantitative image
analysis. We found that juvenile MMP8 null mice had greater mortality and higher
bacterial burden than WT mice. Leukocyte counts and cytokine concentrations in
the peritoneal fluid were increased in the MMP8 null mice, relative to the wild
type mice. Peritoneal macrophages from MMP8 null mice had reduced phagocytic
capacity compared to WT macrophages. There was no quantitative difference in NET
formation, but fewer bacteria were adherent to NETs from MMP8 null animals. In
conclusion, in contrast to septic adult mice, genetic ablation of MMP8 increased
mortality following bacterial peritonitis in juvenile mice. The increase in
mortality in MMP8 null juvenile mice was associated with reduced bacterial
clearance and reduced NET efficiency. We conclude that developmental age
influences the role of MMP8 in sepsis.
PMID- 27506553
TI - The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy.
AB - Mitochondrial functions are intrinsically linked to their morphology and membrane
ultrastructure. Characterizing abnormal mitochondrial structural features may
thus provide insight into the underlying pathogenesis of inherited and acquired
mitochondrial diseases. Following a systematic literature review on
ultrastructural defects in mitochondrial myopathy, we investigated skeletal
muscle biopsies from seven subjects with genetically defined mtDNA mutations.
Mitochondrial ultrastructure and morphology were characterized using two
complimentary approaches: transmission electron microscopy (TEM) and serial block
face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural
abnormalities were identified including i) paracrystalline inclusions, ii)
linearization of cristae and abnormal angular features, iii) concentric layering
of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi)
donut-shaped mitochondria. In light of recent molecular advances in mitochondrial
biology, these findings reveal novel aspects of mitochondrial ultrastructure and
morphology in human tissues with implications for understanding the mechanisms
linking mitochondrial dysfunction to disease.
PMID- 25971900
TI - Current status of automated breast ultrasonography.
AB - Breast ultrasonography (US) is currently considered the first-line examination in
the detection and characterization of breast lesions. However, conventional
handheld US (HHUS) has several limitations such as operator dependence and the
requirement of a considerable amount of radiologist time for whole-breast US.
Automated breast US (ABUS), recently approved by the United States Food and Drug
Administration for screening purposes, has several advantages over HHUS, such as
higher reproducibility, less operator dependence, and less required physician
time for image acquisition. In addition, ABUS provides both a coronal view and a
relatively large field of view. Recent studies have reported that ABUS is
promising in US screening for women with dense breasts and can potentially
replace handheld second-look US in a preoperative setting.
PMID- 25971901
TI - Postoperative ultrasonography of the musculoskeletal system.
AB - Ultrasonography of the postoperative musculoskeletal system plays an important
role in the accurate diagnosis of abnormal lesions in the bone and soft tissues.
Ultrasonography is a fast and reliable method with no harmful irradiation for the
evaluation of postoperative musculoskeletal complications. In particular, it is
not affected by the excessive metal artifacts that appear on computed tomography
or magnetic resonance imaging. Another benefit of ultrasonography is its
capability to dynamically assess the pathologic movement in joints, muscles, or
tendons. This article discusses the frequent applications of musculoskeletal
ultrasonography in various postoperative situations including those involving the
soft tissues around the metal hardware, arthroplasty, postoperative tendons,
recurrent soft tissue tumors, bone unions, and amputation surgery.
PMID- 27506558
TI - Design, synthesis and antimicrobial activity of 6-N-substituted chitosan
derivatives.
AB - Three novel 6-N-substituted chitosan derivatives were designed and synthesised
and characterized by FTIR and NMR. The degree of substitution was calculated by
elemental analysis results. The antimicrobial activities of the target compounds
were evaluated by twofold serial broth dilution method and poisoned food
technique. The antifungal activities of 6-aminoethylamino-6-deoxy chitosan (3), 6
butylamino-6-deoxy chitosan (4) and 6-pyridyl-6-deoxy chitosan (5) were
significantly increased against Rhizoctonia cerealis, Fusarium oxysporum and
Botrytis cinerea, and the inhibition rate ranged from 22.48% to 63.56% at the
concentration of 0.2mg/mL. The compound 3 had better antibacterial activities
than chitosan, and the minimum inhibition concentration of which ranged between
6.25 and 25mg/L against gram-positive bacteria (Staphylococcus aureus, Bacillus
subtilis and Bacillus anthracis) and gram-negative bacteria (Escherichia coli,
Salmonella typhi). The antibacterial activities of 6-N-substituted chitosan
tended to increase with the increase of the number of -NH2 group.
PMID- 27506559
TI - Discovery of ravidasvir (PPI-668) as a potent pan-genotypic HCV NS5A inhibitor.
AB - This Letter describes the synthesis, representative structure activity
relationship (SAR), activity and PK profiles of a series of functionalized
benzimidazole-naphthylene-imidazole derivatives as HCV NS5A inhibitors. This
effort successfully led to the discovery of ravidasvir (PPI-668), which has been
well tolerated and shown high sustained viral response rates as a key component
in all-oral combination regimens in multiple human clinical trials.
PMID- 27506560
TI - The contribution of adenines in the catalytic core of 10-23 DNAzyme improved by
the 6-amino group modifications.
AB - In the catalytic core of 10-23 DNAzyme, its five adenine residues are moderate
conservative, but with highly conserved functional groups like 6-amino group and
7-nitrogen atom. It is this critical conservation that these two groups could be
modified for better contribution. With 2'-deoxyadenosine analogues, several
functional groups were introduced at the 6-amino group of the five adenine
residues. 3-Aminopropyl substituent at 6-amino group of A15 resulted in a five
fold increase of kobs. More efficient DNAzymes are expected by delicate design of
the linkage and the external functional groups for this 6-amino group of A15.
With this modification approach, other functional groups or residues could be
optimized for 10-23 DNAzyme.
PMID- 27506561
TI - Novel pentapeptide, PALAL, derived from a bony fish elicits contraction of the
muscle in starfish Patiria pectinifera.
AB - A bioactive peptide mimicking peptide-signaling molecules has been isolated from
the skin extract of fish Channa argus which caused contraction of the apical
muscle of a starfish Patiria pectinifera, a deuterostomian invertebrate. The
primary structure of the isolated pentapeptide comprises amino acid sequence of H
Pro-Ala-Leu-Ala-Leu-OH (PALAL) with a molecular mass of 483.7 Da. Pharmacological
activity of PALAL, dosage ranging from 10-9 to 10-5 M, revealed concentration
dependent contraction of the apical muscles of P. pectinifera and Asterias
amurensis. However, PALAL was not active on the intestinal smooth muscle of the
goldfish Carassius auratus and has presumably other physiological roles in fish
skin. Investigation of structure-activity relationship using truncated and
substituted analogs of PALAL demonstrated that H-Ala-Leu-Ala-Leu-OH was necessary
and should be sufficient to constrict apical muscle of P. pectinifera.
Furthermore, the second alanine residue was required to display the activity, and
the fifth leucine residue was responsible for its potency. Comparison with
PALAL's primary structure with those of other known bioactive peptides from fish
and starfish revealed that PALAL does not have any significant homology.
Consequently, PALAL is a bioactive peptide that elicits a muscle contraction in
starfish, and the isolation of PALAL may lead to develop other bioactive peptides
sharing its similar sequence and/or activity. Copyright (c) 2016 European Peptide
Society and John Wiley & Sons, Ltd.
PMID- 27506562
TI - Acute pancreatitis and pneumonia due to Mycoplasma pneumoniae: a case report.
AB - BACKGROUND: Mycoplasma pneumoniae is a bacterium responsible for 15 to 40 % of
acute community-acquired pneumonia in children and 20 % of adult cases. Several
extrapulmonary manifestations have been reported. We report a rare case of an
adult patient suffering from pneumonia associated with an acute pancreatitis in
the setting of Mycoplasma pneumoniae infection. CASE PRESENTATION: A 28-year-old
Caucasian woman was referred for anorexia lasting for 1 week. Her past medical
history was notable for congenital hydrocephalus with consecutive ventriculo
peritoneal shunt, epilepsia and paraparesis. The patient rapidly deteriorated,
presenting with dyspnea, tachypnea, productive cough, abdominal pain, and onset
of fever. C-reactive protein was at 270 mg/L, with a rise in serum lipase (670
UI/L, N: 13-60). A computed-tomography scan showed an acute interstitial
edematous pancreatitis without necrosis, consistent with grade C on the Balthazar
score. Thoracic sections revealed diffuse parenchymal consolidations combined
with ground glass opacities. Calcium and triglyceride levels were normal. There
was no history of recent trauma, alcoholic intake or drug intoxication.
Mycoplasma pneumoniae serological assay showed an elevated IgM titer (22 UA/mL),
compatible with recent infection, and cold agglutinins were present. A diagnosis
of acute pancreatitis and diffuse interstitial pneumonia caused by an infection
with Mycoplasma pneumoniae was considered. Respiratory and abdominal evolution
was quickly favorable after initiation of clarithromycin 500 mg bid. CONCLUSIONS:
The relationship between Mycoplasma pneumoniae infection and acute pancreatitis
has been debated in the literature for many years. This observation, supported by
clinical, biological and radiological features, is an additional argument in
favor of a non-fortuitous association.
PMID- 27506563
TI - Poor validity of the routine diagnosis of necrotising enterocolitis in preterm
infants at discharge.
AB - AIM: Necrotising enterocolitis contributes considerably to the mortality of
preterm infants, but most questions remain unsolved after decades of extensive
research. This Danish study investigated the validity of necrotising
enterocolitis diagnoses at discharge according to Bell's staging system. METHODS:
We conducted a retrospective single-centre cohort study of 714 preterm infants
with a gestational age of less than 30 weeks born in 2006-2013. The infants were
diagnosed with necrotising enterocolitis according to Bell's stages 2-3 at
discharge and in retrospect by an expert panel, which served as our gold
standard. RESULTS: The sensitivity of necrotising enterocolitis diagnosed at
discharge was 0.72-0.75 depending on whether spontaneous intestinal perforation
was included as necrotising enterocolitis or not. The positive predictive value
of the diagnosis was 0.49-0.61. The incidence was significantly higher when
diagnosed at discharge than when diagnosed by the expert panel (11.1 versus 9.0%,
p = 0.03). The mortality rate for infants who were underdiagnosed at discharge
was 50.0%, and it was 25.8% for infants who were overdiagnosed (p = 0.10).
CONCLUSION: We found poor validity for the discharge diagnosis of necrotising
enterocolitis. In future, a better way of defining the disease is needed for
large-scale epidemiologic research.
PMID- 27506564
TI - Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension:
Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using
Box-Behnken Design.
AB - Lacidipine (LCDP) is a highly lipophilic calcium channel blocker of poor aqueous
solubility leading to poor oral absorption. This study aims to prepare and
optimize LCDP nanosuspensions using antisolvent sonoprecipitation technique to
enhance the solubility and dissolution of LCDP. A three-factor, three-level Box
Behnken design was employed to optimize the formulation variables to obtain LCDP
nanosuspension of small and uniform particle size. Formulation variables were as
follows: stabilizer to drug ratio (A), sodium deoxycholate percentage (B), and
sonication time (C). LCDP nanosuspensions were assessed for particle size, zeta
potential, and polydispersity index. The formula with the highest desirability
(0.969) was chosen as the optimized formula. The values of the formulation
variables (A, B, and C) in the optimized nanosuspension were 1.5, 100%, and 8
min, respectively. Optimal LCDP nanosuspension had particle size (PS) of 273.21
nm, zeta potential (ZP) of -32.68 mV and polydispersity index (PDI) of 0.098.
LCDP nanosuspension was characterized using x-ray powder diffraction,
differential scanning calorimetry, and transmission electron microscopy. LCDP
nanosuspension showed saturation solubility 70 times that of raw LCDP in addition
to significantly enhanced dissolution rate due to particle size reduction and
decreased crystallinity. These results suggest that the optimized LCDP
nanosuspension could be promising to improve oral absorption of LCDP.
PMID- 27506565
TI - Influence of Hydroalcoholic Vehicle on In Vitro Transport of 4-Hydroxy Tamoxifen
Through the Mammary Papilla (Nipple).
AB - Majority of breast cancers originate from epithelial cells in the duct and
lobules in the breast. Current systemic treatments for breast cancer are
associated with significant systemic side effects, thus warranting localized drug
delivery approaches. The aim of this study was to investigate the influence of
hydroalcoholic vehicle on topical delivery of 4-hydroxy tamoxifen (4-HT) through
the mammary papilla (nipple). The in vitro permeability of 4-HT through porcine
mammary papilla was studied using different hydroalcoholic vehicles (0, 33.33,
and 66.66% alcohol). Nile red was used as a model lipophilic dye to characterize
the drug transport pathway in the mammary papilla. The penetration of 4-HT
through the mammary papilla increased with increase in alcohol concentration in
the vehicle. The solubility of 4-HT was enhanced by increasing alcohol
concentration in the vehicle. On the other hand, the epidermis/vehicle partition
coefficient decreased with increase in alcohol concentration. The mammary papilla
served as a depot and slowly released 4-HT into the receptor medium. Highest drug
penetration was observed with saturated drug solution in 66.66% alcohol, and 4-HT
levels were comparable to IC50 value of 4-HT. Results from this study demonstrate
the possibility of using mammary papilla as a potential route for direct delivery
of 4-HT to the breast.
PMID- 27506566
TI - Letter to the editor of infection in response to de Francesco et al., a cluster
of invasive listeriosis in Brescia, Italy.
PMID- 27506568
TI - Advances in the development of catalytic tethering directing groups for C-H
functionalization reactions.
AB - Transition metal-catalyzed C-H bond insertion is one of the most straightforward
strategies to introduce functionalities within a hydrocarbon microenvironment.
For the past two decades, selective activation and functionalization of certain
inert C-H bonds have been made possible with the help of directing groups (DGs).
Despite the enormous advances in the field, an overwhelming majority of systems
require two extra steps from their simple precursors: installation and removal of
the DGs. Recently, traceless and multitasking groups were invented as a partial
solution to DG release. However, installation remains largely unsolved. Ideally,
a transient, catalytic DG would circumvent this problem and increase the step-
and atom-economy of C-H functionalization processes. In this review, we summarize
the recent development of the transient tethering strategy for C-H activation
reactions.
PMID- 27506567
TI - Does the intraocular pressure-lowering effect of prostaglandin analogues continue
over the long term?
AB - The purpose of the study is to assess the changes in the long-term effects of
prostaglandin analogues (PGAs) on intraocular pressure (IOP) reduction in
patients with primary open-angle glaucoma (POAG). Data of POAG patients treated
with latanoprost (0.005 %), travoprost (0.004 %), or bimatoprost (0.03 %) as the
first line treatment for 5 years or more were retrospectively evaluated. Baseline
ophthalmic assessment values were recorded together with the IOP at the 6th
month, 1st year, and then annually. The 79 patients included 33 (41.8 %) men and
46 (58.2 %) women. There were 34 (43.0 %) patients using latanoprost (0.005 %),
23 (29.1 %) patients using bimatoprost (0.03 %), and 22 (27.8 %) patients using
travoprost (0.004 %). There was no difference between the groups in terms of age,
gender, or baseline IOP levels. IOP levels at the 6th month were significantly
lower than baseline IOP levels in all groups (p < 0.01, Friedman test). The IOP
decrease was maintained after the 6th month in all three group with no
statistically significant difference compared to the 6th month IOP value (p >
0.05, Friedman test) and no statistically significant difference between the
groups during follow-up (Kruskal-Wallis test, p > 0.05). IOP reductions with PGAs
were adequate and stable in the 5-year follow-up period with no decrease in
effectiveness over time.
PMID- 27506569
TI - Complications of elastic stable intramedullary nailing of femoral shaft fractures
in children weighing fifty kilograms (one hundred and ten pounds) and more.
AB - AIM: The purpose of this study was to assess treatment outcomes in children
weighing 50 kg (110 pounds) or more with displaced femur shaft fractures treated
by elastic stable intramedullary nailing (ESIN) and to identify potential
correlations between nail size/medullary canal diameter ratio and outcome.
METHODS: Twenty out of 117 consecutive children surgically treated by ESIN for
displaced fractures of the femoral shaft with no associated neurovascular injury
weighed 50 kg (110 pounds) or more. All patients underwent regular clinical and
radiographic follow-up for at least one year after their index surgery. RESULTS:
The average patient age at the time of injury was 13.1 years (25th and 75th
interquartile range [IQR] = 11.7-14.5). The mean follow-up was 27.4 months (IQR =
18.4-36.8). Overall, nine (45 %) adverse events were observed. The rate of
complications was higher among children weighting 55 kg and over (67 %) than in
children weighing less than 55 kg (35 %) and among children aged 13 years old or
older (72 %) than among children younger than 13 years old (11 %). DISCUSSION:
Femoral shaft fractures in children and adolescents weighing 50 kg (110 pounds)
and over and older than ten years of age have an increased rate of complications.
CONCLUSION: Heavier patients have a greater chance of complications. In
particular, patients younger than 13 years old and weighing less than 55 kg can
be safely managed with ESIN, but older and heavier patients should preferably be
treated with rigid fixation systems due to a greater complication rate. However,
further studies are needed to consolidate the conclusions.
PMID- 27506570
TI - Treatment of displaced supracondylar humeral fractures in children by humero
ulnar external fixation.
AB - PURPOSE: Humero-ulnar external fixation has been proposed to treat complex
supracondylar humeral fractures in children. It facilitates fracture reduction
and reduces the risk of ulnar nerve lesion, which can occur after cross pinning.
METHODS: In a ten year period, 28 children have been operated on in our centre by
humero-ulnar external fixation, for Lagrange-Rigault stages III and IV
supracondylar humeral fractures. The data about fracture management and early
follow-up were obtained from our medical database. The long-term evaluation was
done at a minimum six months' follow-up. The range of motion and carrying angle
measurements were classified according to Flynn. The final X-rays were evaluated
for quality of reduction, presence of malunion, late infection signs, osteo
arthritis and myositis ossificans. The elbow function was evaluated by Mayo Elbow
Performance Index (MEPI), Disabilities of the Arm, Shoulder and Hand (DASH) or
modified DASH scores. RESULTS: The treatment was well tolerated by children and
parents. There was no neurological complication related to the insertion of the
pins, and no Volkmann syndrome. The median duration of external fixation was 33.5
days. Twelve patients were reviewed after a median follow-up duration of seven
years (mean, 7.5 years; range, 3-21 years). One child had a refracture, three
years after his original fracture, which was treated non-operatively. This case
ended up in a cubitus varus deformity with a pronation deficit. All other
patients had excellent clinical and radiological results. CONCLUSIONS: For the
treatment of complex supracondylar humeral fractures in children, humero-ulnar
external fixation is a good alternative to lateral or crossed pinning. The
advantages are the ease to obtain the reduction, the absence of neurological risk
to the ulnar nerve and the possibility to obtain good stabilisation of the
fracture with moderate elbow flexion.
PMID- 27506571
TI - Early aseptic loosening of cementless monoblock acetabular components.
AB - PURPOSE: Early aseptic loosening of cementless monoblock acetabular components is
a rare complication of total hip arthroplasty (THA) and hip resurfacing
arthroplasty (HRA). The purpose of this study was to evaluate the incidence and
risk factors for early aseptic loosening of the cementless monoblock acetabular
components. METHODS: This retrospective analysis consisted of 4,043 cementless
hip devices (3,209 THAs and 834 HRAs). We identified 41 patients with early
aseptic loosening of the acetabular component. A control group of 123 patients
without acetabular component loosening was randomly selected. The demographic
data and risk factors for loosening of the acetabular component were evaluated.
The mean follow-up time was 4.6 years (range, 1.7-7.8). The end-point was
acetabular revision. RESULTS: The incidence of early acetabular component
loosening was 1.0 %. Mean time to revision was 1.2 years (SD 1.6, range 0.0-5.4).
There was significantly more Dorr type A and C acetabular morphology in patients
with early loosening (P = 0.014). The loosened components were implanted to more
vertical (P < 0.001) and less anteverted (P = 0.001) position than those of the
control group. Presence of acetabular dysplasia or acetabular component type did
not associate to early loosening. CONCLUSIONS: Acetabular morphology (Dorr type A
and C) and component positioning vertically and less anteverted were more common
in patients with early aseptic loosening of cementless acetabular components.
Suboptimal cup position most likely reflects challenges to obtain sufficient
stability during surgery. We hypothesize that errors in surgical technique are
the main reason for early loosening of monoblock acetabular components.
PMID- 27506572
TI - Total shoulder replacement using a bone ingrowth central peg polyethylene glenoid
component: a prospective clinical and computed tomography study with short- to
mid-term follow-up.
AB - AIM OF THE STUDY: To assess the clinical and computed tomography (CT) outcomes of
shoulder replacement with a novel bone ingrowth all-polyethylene glenoid
component (APGC). METHODS: Twenty-eight patients (30 shoulders) with
osteoarthritis, mean age 62.3 years (range, 45-75), were implanted with the novel
component between 2011 and 2013. Patients were evaluated by active range of
motion (ROM), Constant-Murley score (CMS), simple shoulder test (SST), X-rays,
and multidetector CT at two months and at a mean follow-up of 31 months (range,
24-39). Early and late follow-up CT scans were available for 21/30 shoulders.
RESULTS: Median ROM increased from 105 to 160 degrees for anterior elevation,
from 100 to 160 degrees for lateral elevation, from 20 to 40 degrees for
external rotation, and from 2 to 10 points for internal rotation (all p < 0.001).
CMS rose from 30 to 80.5 points and SST from 2.5 to 11 (both p < 0.0001). None of
the glenoid components migrated. Progressive radiolucency was seen in 28/30
shoulders. There was a strong correlation between greater bone ingrowth (median
Arnold score: 7) and lower radiolucency score (median Yian score: 2) at the last
follow-up (p < 0.001). Osteolysis around the central peg was seen in two
shoulders. There was no correlation between clinical scores and CT findings (p
>0.05). DISCUSSION: The partially cemented glenoid component for TSR assessed in
this study resulted in satisfactory shoulder function at an early follow-up. The
glenoid prosthesis was stable, with few radiolucent lines and good central peg
bone ingrowth. CONCLUSIONS: The satisfactory bone ingrowth documented on CT is
encouraging and supports the use of the new prosthesis. Long-term follow-up
studies can confirm if this device represents a rational alternative to fully
cemented polyethylene glenoids.
PMID- 27506573
TI - Eudesmane-type sesquiterpenoids from Salvia plebeia inhibit IL-6-induced STAT3
activation.
AB - Seven eudesmane-type sesquiterpenoid lactones and the known plebeiolide C were
isolated from an ethanol-soluble extract of the aerial parts of Salvia plebeia R.
Br. Their structures were determined via NMR and MS, and their absolute
configurations were elucidated using ECD, and X-ray crystallographic analysis, as
well as the modified Mosher ester method. All isolates were evaluated for their
inhibitory effects on IL6-induced STAT3 promoter activation in stably transfected
Hep3B cells. Of these isolates, eudebeiolide D exhibited an inhibitory effect
with the IC50 value of 1.1 MUM.
PMID- 27506574
TI - Features and Application in Asymmetric Catalysis of Chiral Phosphine-Phosphite
Ligands.
AB - Chiral phosphine-phosphites are a class of ligands for asymmetric catalysis
characterized by two coordinating functionalities with different electronic
properties. These ligands also possess a highly modular structure and, due to
versatile synthetic processes, they can be tuned precisely in the catalyst
optimization process. Research regarding the application of these ligands in
several enantioselective catalytic processes has provided outstanding results in
a good number of them. These processes include not only Rh catalyzed reactions,
such as olefin hydrogenation and hydroformylation, but also other reactions, such
as hydrogenation of olefins and imines by Ru complexes, of imines and N
heterocycles by Ir derivatives, allyl alkylation or conjugate addition by Cu
catalysts, or hydrocyanation of olefins by Ni ones. Overall, the use of these
ligands has led to the preparation of a wide variety of chiral building blocks
with high enantiomeric excess. Therefore, phosphine-phosphites have become in an
important class of ligands in asymmetric catalysis.
PMID- 27506575
TI - Free-Radical-Assisted Rapid Synthesis of Graphene Quantum Dots and Their
Oxidizability Studies.
AB - This work reports a modified electrochemical method for rapid and large-scale
preparing graphene quantum dots (GQDs) by introduction of active free radicals,
which were produced by hydrogen peroxide or ultraviolet radiation. These free
radicals can deepen the oxidized or reduced level of working electrode in
electrochemical process and thus lead to GQDs with high concentration and small
size, but different surface oxidized degree. The improved oxidation and reduction
mechanism were analyzed in this work. Meanwhile, the optical properties and
oxidizability of GQDs with different surface oxidized degree were investigated.
It is found that these GQDs can be used as an oxidizing agent and their
oxidizability is related to the degree being oxidized.
PMID- 27506576
TI - Citation for the 2015 Down Surgical Prize: Professor Velupillai Ilankovan.
PMID- 27506577
TI - Aerobic metabolism on muscle contraction in porcine iris sphincter.
AB - Eyes are supplied O2 through the cornea and vessels of the retina and iris, which
are tissues characterized by aerobic metabolism. Meanwhile, there are no reports
on the association between iris sphincter contraction and aerobic metabolism. In
this paper, we studied the aforementioned association. Eyes from adult pigs of
either sex were obtained from a local abattoir. A muscle strip was connected to a
transducer to isometrically record the tension. O2 consumption was measured using
a Clark-type polarograph connected to a biological oxygen monitor. Creatine
phosphate (PCr) and adenosine triphosphate (ATP) contents were measured in the
muscle strips by high-performance liquid chromatography (HPLC). Iris sphincter
muscles were measured in resting, contractile or hypoxic phases. Contraction was
induced by hyperosmotic 65 mM KCl (H-65K+) or carbachol (CCh), and hypoxia was
induced by aeration with N2 instead of O2 or by addition of sodium cyanide
(NaCN). H-65K+- and CCh-induced muscle contraction, involved increasing O2
consumption. Hypoxia and NaCN significantly decreased H-65K+- and CCh-induced
muscle contraction and/or O2 consumption and PCr contents. Our results suggest
that the contractile behavior in porcine iris sphincter highly depends on mitogen
oxidative metabolism.
PMID- 27506578
TI - TRPV4 ion channel as important cell sensors.
AB - This review provides a summary of the physiological significance of the TRPV4 ion
channel. Although TRPV4 was initially characterized as an osmosensor, we found
that TRPV4 can also act as a thermosensor or a mechanosensor in brain neurons or
epithelial cells in the urinary bladder. Here, we summarize the newly
characterized functions of TRPV4, including the research progress that has been
made toward our understanding of TRPV4 physiology, and discuss other recent data
pertaining to TRPV4. It is thought that TRPV4 may be an important drug target
based on its broad expression patterns and important physiological functions.
Possible associations between diseases and TRPV4 are also discussed.
PMID- 27506579
TI - Variation in primary site resection practices for advanced colon cancer: a study
using the National Cancer Data Base.
AB - BACKGROUND: Treatment of metastatic colon cancer may be driven as much by
practice patterns as by features of disease. To optimize management, there is a
need to better understand what is determining primary site resection use.
METHODS: We evaluated all patients with stage IV cancers in the National Cancer
Data Base from 2002 to 2012 (50,791 patients, 1,230 hospitals). We first
identified patient characteristics associated with primary tumor resection. Then,
we assessed nationwide variation in hospital resection rates. RESULTS: Overall,
27,387 (53.9%) patients underwent primary site resection. Factors associated with
resection included younger age, having less than 2 major comorbidities, and white
race (P < .001). Nationwide, hospital-adjusted primary tumor resection rates
ranged from 26.0% to 87.8% with broad differences across geographical areas and
hospital accreditation types. CONCLUSIONS: There is statistically significant
variation in hospital rates of primary site resection. This demonstrates
inconsistent adherence to guidelines in the presence of conflicting evidence
regarding resection benefit.
PMID- 27506580
TI - Using fundamental frequency of cancer survivors' speech to investigate emotional
distress in out-patient visits.
AB - OBJECTIVE: Emotions, are in part conveyed by varying levels of fundamental
frequency of voice pitch (f0). This study tests the hypothesis that patients
display heightened levels of emotional arousal (f0) during Verona Coding
Definitions of Emotional Sequences (VR-CoDES) cues and concerns versus during
neutral statements. METHODS: The audio recordings of sixteen head and neck cancer
survivors' follow-up consultations were coded for patients' emotional distress.
Pitch (f0) of coded cues and concerns, including neutral statements was
extracted. These were compared using a hierarchical linear model, nested for
patient and pitch range, controlling for statement speech length. Utterance
content was also explored. RESULTS: Clustering by patient explained 30% of the
variance in utterances f0. Cues and concerns were on average 13.07Hz higher than
neutral statements (p=0.02). Cues and concerns in these consultations contained
content with a high proportion of recurrence fears. CONCLUSION: The present study
highlights the benefits and challenges of adding f0 and potential other prosodic
features to the toolkit of coding emotional distress in the health communication
setting. PRACTICE IMPLICATIONS: The assessment of f0 during clinical
conversations can provide additional information for research into emotional
expression.
PMID- 27506581
TI - Cancer patients' understanding of longitudinal EORTC QLQ-C30 scores presented as
bar charts.
AB - OBJECTIVE: To investigate cancer patients' understanding of graphical
presentations of longitudinal EORTC QLQ-C30 scores. METHODS: We conducted semi
structured interviews with brain tumour patients participating in routine patient
reported outcome (PRO) monitoring. We assessed understanding of longitudinal
quality of life (QOL) profiles, presented as bar charts objectively and with self
ratings. In addition, patients' opinions on congruency of the QOL scores with
their self-perceived health status were evaluated. RESULTS: We recruited 40 brain
tumour patients (57.5% female; mean age 52.7, SD 13.7). In total, 90% of patients
rated the graphs as easy to understand. Accordingly, almost all questions on
assessing understanding objectively were answered correctly by at least 80% of
the patients. More than 95% indicated that the displayed QOL scores matched their
personal perception of symptom burden and functional health in the observed
period. CONCLUSION: Patients are able to understand their QOL results when
presented graphically and are able to interpret important changes. Displayed QOL
scores obtained with the EORTC QLQ-C30 are consistent with the patients' personal
perception of physical and emotional functioning, pain and fatigue. PRACTICE
IMPLICATIONS: Knowledge about patients' understanding of graphically displayed
QOL results contributes to creation of optimal evidence-based feedback on the
patients' present QOL and its trajectory.
PMID- 27506582
TI - A multiplex real-time PCR panel assay for simultaneous detection and
differentiation of 12 common swine viruses.
AB - Mixed infection with different pathogens is common in swine production systems
especially under intensive production conditions. Quick and accurate detection
and differentiation of different pathogens are necessary for epidemiological
surveillance, disease management and import and export controls. In this study,
we developed and validated a panel of multiplex real-time PCR/RT-PCR assays
composed of four subpanels, each detects three common swine pathogens. The panel
detects 12 viruses or viral serotypes, namely, VSV-IN, VSV-NJ, SVDV, CSFV, ASFV,
FMDV, PCV2, PPV, PRV, PRRSV-NA, PRRSV-EU and SIV. Correlation coefficients (R(2))
and PCR amplification efficiencies of all singular and triplex real-time PCR
reactions are within the acceptable range. Comparison between singular and
triplex real-time PCR assays of each subpanel indicates that there is no
significant interference on assay sensitivities caused by multiplexing.
Specificity tests on 226 target clinical samples or 4 viral strains and 91 non
target clinical samples revealed that the real-time PCR panel is 100% specific,
and there is no cross amplification observed. The limit of detection of each
triplex real-time PCR is less than 10 copies per reaction for DNA, and less than
16 copies per reaction for RNA viruses. The newly developed multiplex real-time
PCR panel also detected different combinations of co-infections as confirmed by
other means of detections.
PMID- 27506583
TI - Biomass and productivity of fishes in estuaries: a South African case study.
AB - Estuaries are well known for their role as nutrient and detrital sinks that
stimulate high levels of both primary and secondary production which, in turn,
support a large biomass of fishes per unit area. This study reviews available
information on coastal fish biomasses (g m-2 wet mass) and productivity (g m-2
wet mass year-1 ) in order to place South African data on these topics into a
global perspective. Using biogeographic fish productivity estimates, together
with estuarine water area, the approximate annual teleost production in South
African estuaries was calculated at 585, 1706 and 13 904 t in the cool temperate,
warm temperate and subtropical regions, respectively. Total annual fish
production in estuaries on the subcontinent is conservatively estimated at 16 195
t, but this figure is likely to fluctuate widely, depending on recruitment
success and annual environmental conditions pertaining to these systems.
Approximately 2000 t of fish are estimated to be harvested by fishing activities
in South African estuaries each year, which represents c. 12% of annual fish
production. Although this figure may appear sustainable, the reality is that
there are a few heavily targeted estuary-associated marine species at the top of
the food chain that are being overexploited by both anglers and subsistence
fishermen. Natural mortalities due to piscivorous fish and bird predation has
been estimated at c. 3% of total fish biomass per month in the East Kleinemonde
Estuary, but this figure will vary considerably depending on bird abundance and
foraging patterns along the coast. In contrast to catches made by the fishermen,
piscivorous fishes and birds are targeting mainly juvenile marine fish and small
estuarine resident species that are very abundant and generally low down in the
food web.
PMID- 27506584
TI - Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1
diabetes.
AB - AIMS/HYPOTHESIS: Human pancreatic beta cells may be complicit in their own demise
in type 1 diabetes, but how this occurs remains unclear. One potentially
contributing factor is hyperexpression of HLA class I antigens. This was first
described approximately 30 years ago, but has never been fully characterised and
was recently challenged as artefactual. Therefore, we investigated HLA class I
expression at the protein and RNA levels in pancreases from three cohorts of
patients with type 1 diabetes. The principal aims were to consider whether HLA
class I hyperexpression is artefactual and, if not, to determine the factors
driving it. METHODS: Pancreas samples from type 1 diabetes patients with residual
insulin-containing islets (n = 26) from the Network for Pancreatic Organ donors
with Diabetes (nPOD), Diabetes Virus Detection study (DiViD) and UK recent-onset
type 1 diabetes collections were immunostained for HLA class I isoforms, signal
transducer and activator of transcription 1 (STAT1), NLR family CARD domain
containing 5 (NLRC5) and islet hormones. RNA was extracted from islets isolated
by laser-capture microdissection from nPOD and DiViD samples and analysed using
gene-expression arrays. RESULTS: Hyperexpression of HLA class I was observed in
the insulin-containing islets of type 1 diabetes patients from all three tissue
collections, and was confirmed at both the RNA and protein levels. The expression
of beta2-microglobulin (a second component required for the generation of
functional HLA class I complexes) was also elevated. Both 'classical' HLA class I
isoforms (i.e. HLA-ABC) as well as a 'non-classical' HLA molecule, HLA-F, were
hyperexpressed in insulin-containing islets. This hyperexpression did not
correlate with detectable upregulation of the transcriptional regulator NLRC5.
However, it was strongly associated with increased STAT1 expression in all three
cohorts. Islet hyperexpression of HLA class I molecules occurred in the insulin
containing islets of patients with recent-onset type 1 diabetes and was also
detectable in many patients with disease duration of up to 11 years, declining
thereafter. CONCLUSIONS/INTERPRETATION: Islet cell HLA class I hyperexpression is
not an artefact, but is a hallmark in the immunopathogenesis of type 1 diabetes.
The response is closely associated with elevated expression of STAT1 and,
together, these occur uniquely in patients with type 1 diabetes, thereby
contributing to their selective susceptibility to autoimmune-mediated
destruction.
PMID- 27506585
TI - Leukocyte-poor platelet-rich plasma is more effective than the conventional
therapy with acetaminophen for the treatment of early knee osteoarthritis.
AB - INTRODUCTION: Knee osteoarthritis (OA) is a degenerative and progressive
articular cartilage disease. Infiltration of autologous platelet-rich plasma
(PRP) has been proposed as a therapeutic alternative due to the content of
biologically active cytokines in PRP. We aimed to compare the clinical response
of acetaminophen and intra-articular leukocyte-poor PRP (LP-PRP) in early knee
OA. MATERIALS AND METHODS: A total of 65 patients with clinically and
radiographically documented knee OA (grade 1-2) were analyzed. Patients were
randomized into two groups: 32 were treated with acetaminophen (500 mg/8 h) over
6 weeks, and 33 received three intra-articular injections of autologous LP-PRP
(once every 2 weeks). All patients were evaluated by the Visual Analogue Scale
(VAS), the Western Ontario and McMaster Universities (WOMAC) score, and the SF-12
health survey at baseline and 6, 12, and 24 weeks of follow-up. All LP-PRP
preparations were analyzed for the platelet, leukocyte, IL-1ra, and TGF-beta
concentrations. RESULTS: The decrease in the VAS pain level in the LP-PRP group
was greater than that in the acetaminophen group (p < 0.05). Patients treated
with LP-PRP showed a sustained improvement in knee function at week 24 (p <
0.01). The SF-12 results only indicated an improvement in quality-of-life in the
LP-PRP group at 6, 12, and 24 weeks of follow-up (p < 0.01). Both IL-1ra and TGF
beta were detected in the LP-PRP samples (313.8 +/- 231.6 and 21,183.8 +/- 8556.3
pg/mL, respectively). CONCLUSIONS: Treatment with LP-PRP injections resulted in a
significantly better clinical outcome than did treatment with acetaminophen, with
sustained lower EVA and WOMAC scores and improvement in quality-of-life (higher
SF-12 score). Therapy with LP-PRP may positively modify the inflammatory joint
environment by counteracting IL-1beta action.
PMID- 27506586
TI - Differentiating acute ischemic lesions from mitochondrial stroke-like lesions on
3D pseudo-continuous arterial spin labelling.
PMID- 27506588
TI - In vitro effects of different sources of fibrinogen supplementation on clot
initiation and stability in a model of dilutional coagulopathy.
AB - OBJECTIVES: To analyse which fibrinogen source may improve coagulation using an
in vitro 33% dilutional coagulopathy model. BACKGROUND: Uncritical volume
resuscitation in the context of trauma haemorrhage contributes to the iatrogenic
arm of the acute trauma-induced coagulopathy through dilution and depletion of
coagulation factors, with fibrinogen reaching critical levels first. MATERIALS
AND METHODS: By using an experimental model of 33% dilutional coagulopathy, we
have analysed which fibrinogen source may exert superior effects on improving
haemocoagulative capacities and correcting depleted fibrinogen levels. As
fibrinogen sources, we supplemented (i) fresh frozen plasma (FFP), (ii)
fibrinogen concentrate low-dose (Fiblow ) and (iii) fibrinogen concentrate high
dose (Fibhigh ), the latter both in the presence and absence of additional FXIII.
RESULTS: The dilution was associated with decreased haemoglobin and haematocrit
levels. Fibrinogen supplementation with fibrinogen-containing formulations led to
increased fibrinogen levels (FFP: 172.2 +/- 17.4 mg dL-1 ; Fiblow : 211.5 +/-
20.61 mg dL-1 ; Fibhigh : 255.8 +/- 21.4 mg dL-1 ) than in a diluted-only sample
(155.5 +/- 19.7 mg dL-1 ). Extrinsically activated assay with tissue factor
(EXTEM) clot formation times, alpha-angles and maximum clot firmness
significantly improved in the groups of Fiblow + FXIII (79 +/- 12.2 s; 74.3 +/-
2.4 degrees ; 62 +/- 2.3 mm), Fibhigh (70.8 +/- 10.6 s; 76.2 +/- 2.7 degrees ;
64.3 +/- 2.3 mm) and Fibhigh + FXIII (69.8 +/- 11.5 s; 77.5 +/- 2.7 degrees ;
64.33 +/- 2.5 mm) compared with the dilution groups (104.2 +/- 19 s; 69.7 +/- 2.9
degrees ; 56.5 +/- 3.1 mm). In contrast, rotational thromboelastometric trace
(ROTEM) measures of samples supplemented with FFP largely remained unchanged.
CONCLUSION: Fibrinogen concentrates corrected and improved haemodilution-induced
changes in blood clotting in vitro. High-dose fibrinogen supplementation was
associated with correction and improvement in clot dynamics and stability.
PMID- 27506587
TI - Melanoma Expression Genes Identified through Genome-Wide Association Study of
Breslow Tumor Thickness.
PMID- 27506589
TI - Sympathetic neural and cardiovascular responses during static handgrip exercise
in women with a history of hypertensive pregnancy.
AB - PURPOSE: Women with a history of hypertensive pregnancy are at greater risk for
future cardiovascular events; however, the mechanisms for this increased risk are
unknown. Evidence suggests that an exercise stimulus unmasks latent hypertensive
tendencies, identifying individuals at the greatest risk for developing
cardiovascular disease. The current study examined the hypothesis that women with
a hypertensive pregnancy history exhibit an augmented exercise pressor response.
METHODS: Normotensive women with a history of healthy pregnancy (CON; n = 9) and
hypertensive pregnancy (HP+; n = 12) were studied during the mid-luteal phase of
the menstrual cycle. Heart rate (HR), systolic and diastolic blood pressure (SBP,
DBP), and muscle sympathetic nerve activity (MSNA) were measured during a cold
pressor test (CPT), and, following a sufficient period of recovery, during static
handgrip to fatigue (SHG) and post-exercise circulatory arrest (PECA). RESULTS:
The BP, HR, and MSNA responses to the CPT were similar between groups. The SBP
response to SHG and PECA was similar between groups, but DBP and HR were
significantly greater in HP+ women (both p < 0.05). MSNA burst frequency, but not
burst incidence or total activity, tended to be elevated in HP+ women during the
stressor (peak Delta from baseline 31 +/- 13 vs. 23 +/- 13 bursts/min; p for
group = 0.06). CONCLUSION: Despite no clinical signs of cardiovascular disease or
hypertension, women with a history of hypertensive pregnancy display an enhanced
cardiovascular reactivity to an exercise stimulus compared to women with a
healthy pregnancy history. This response may be indicative of impaired
cardiovascular control that precedes the clinical manifestation of hypertension
or cardiovascular events.
PMID- 27506590
TI - Microbacterium aureliae sp. nov., a novel actinobacterium isolated from Aurelia
aurita, the moon jellyfish.
AB - The taxonomic position of a lemon-yellow-pigmented actinobacterium, strain JF-6T,
isolated from Aurelia aurita, the moon jellyfish, collected from the Bay of
Bengal coast, Kanyakumari, India, was determined using a polyphasic approach. The
strain had phenotypic and chemotaxonomic properties that were consistent with its
classification in the genus Microbacterium. Alignment of the 16S rRNA gene
sequence of strain JF-6T with sequences from Microbacterium arthrosphaerae CC-VM
YT, Microbacterium yannicii G72T, Microbacterium trichothecenolyticum IFO 15077T,
Microbacterium flavescens DSM 20643T, Microbacterium insulae DS-66T,
Microbacterium resistens DMMZ 1710T and Microbacterium thalassium IFO 16060T
revealed similarities of 98.95, 98.76, 98.43, 98.41, 98.41, 98.26 and 98.22 %,
respectively. However, the levels of DNA-DNA relatedness with its closest
phylogenetic neighbours confirmed that it represents a novel species within the
genus. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol
and an unknown glycolipid. The major menaquinones detected for strain JF-6T were
MK-13 and MK-12. The diamino acid in the cell-wall peptidoglycan was ornithine
and the peptidoglycan was type B2beta (Glu/Hyg-Gly-d-Orn). The DNA G+C content
was 69.4 mol%. Based on these differences, strain JF-6T (=MTCC 11843T=JCM
30060T=KCTC 39828T) should be classified as the type strain of a novel species of
Microbacterium, for which the name Microbacterium aureliae sp. nov. is proposed.
PMID- 27506591
TI - M1 polarization and the effect of PGE2 on TNF-alpha production by lymph node
cells from dogs with visceral leishmaniasis.
AB - Canine visceral leishmaniasis (CVL) is caused by the intracellular parasite
Leishmania infantum. Increased levels of arginase, nitric oxide (NO2 ) and
prostaglandin E2 (PGE2 ) can play a regulatory role regarding the immune response
in CVL cases. This study aimed to evaluate the arginase activity in adherent
macrophages cultured from the lymph nodes of healthy and naturally infected dogs
and to examine the NO2 and PGE2 levels in the supernatant of these cultures. In
addition, the regulatory effect of PGE2 on the production of tumour necrosis
factor (TNF-alpha) and interleukin-10 (IL-10) in supernatants from the total
lymph node was observed in leucocyte cultures. The arginase activity was lower in
the adherent macrophages cultured from the lymph nodes of naturally infected dogs
and there were higher concentrations of NO2 and PGE2 in the supernatants of these
cultures. Higher TNF-alpha and IL-10 concentrations were observed in supernatants
from total lymph node leucocytes cultures, from infected dogs, and the presence
of indomethacin only decreased TNF-alpha in the supernatant of these cultures. We
conclude that the low arginase activity in macrophages suggested that M1
polarization and PGE2 were participating in the immune response and were
increasing TNF-alpha in CVL.
PMID- 27506592
TI - An efficient hydrogenation catalyst in sulfuric acid for the conversion of
nitrobenzene to p-aminophenol: N-doped carbon with encapsulated molybdenum
carbide.
AB - The transfer of catalytic function from molybdenum carbide to N-doped carbon has
been tested by encapsulating molybdenum carbide with N-doped carbon using a one
pot preparation process. The outer layer of N-doped carbon, inert itself,
exhibits high activity and excellent selectivity with molybdenum carbide as the
catalyst for the hydrogenation of nitrobenzene to p-aminophenol in sulfuric acid.
PMID- 27506593
TI - The burden of disease of dental anxiety: generic and disease-specific quality of
life in patients with and without extreme levels of dental anxiety.
AB - The aim of this study was to compare disease-specific (oral health-related)
quality of life (OHRQoL), assessed using the Oral Health Impact Profile-14 (OHIP
14), and generic (health-related) quality of life (HRQoL), assessed using the
EuroQol5D (EQ-5D-5L), in patients with severe dental anxiety (who were visiting a
centre for special care dentistry) with a control group from the general
population. Seventy-six patients with severe dental anxiety [Dental Anxiety Scale
(DAS) score >= 13] were matched, according to age, gender, and socio-economic
status, to a control group of 76 participants in a larger epidemiological study
on oral health in the Netherlands (n = 1,125). The Wilcoxon signed-rank test was
used to compare levels of HRQoL and OHRQoL in both groups. The total OHIP score
(indicating lower OHRQoL) was higher for the patient group (10th percentile =
30.5; 90th percentile = 46.0) than for the control group (10th percentile = 1.0;
90th percentile = 14.5). The patient group showed higher scores on all seven OHIP
domains. Lower utility scores were found in patients with severe dental anxiety
(HRQOL: 10th percentile = 0.7; 90th percentile = 0.9) relative to the control
group (HRQOL: 10th percentile = 0.9; 90th percentile = 1.0). A disease burden of
74,000 disability-adjusted life years (DALYs) was calculated for the Netherlands.
The findings of this study show differences between patients visiting a dental
fear clinic and matched controls from the general population for both OHRQoL and
HRQoL, indicating that having severe dental anxiety generates a significant
burden of disease.
PMID- 27506594
TI - Combining fibroblast isolation with lentiviral gene transfer to validate
transgene expression in mice following pronucleus injection.
AB - The binary tetracycline-based expression system in transgenic mice relies on the
expression of the tetracycline transactivator (tTA or rtTA) in a particular cell
type together with a transcription unit encoding the gene of interest under a
tetracycline or doxycycline-responsive promoter. Transgenic mice containing this
transcription unit are produced via pronucleus injection. As the chromosomal
integration site of the injected DNA influences transgene expression, several
founder lines have to be crossed with (r)tTA-expressing mice to find a line
showing low background and high transgene expression following doxycycline
stimulation. Here, we describe a method to analyze primary fibroblasts derived
from the founder lines to quickly test transgene expression and inducibility.
Fibroblasts isolated from a small piece of mouse ear were infected with a
recombinant lentivirus expressing rtTA. Transgene expression was verified by both
RT-PCR and western blot, following stimulation with doxycycline. Transgene
expression could easily be detected on the RNA and protein levels in primary
fibroblasts derived from transgenic founder lines. An enzymatic function of the
transgene was not required for the identification of transgene expression. Thus,
the method allows a quick and easy discrimination of transgenic founder lines
according to transgene expression and inducibility.
PMID- 27506595
TI - Effect of DNA on the conformational dynamics of the endonucleases I-DmoI as
provided by molecular dynamics simulations.
AB - The conformational behavior of the wild-type endonucleases I-DmoI and two of its
mutants has been studied in the presence and in the absence of DNA target
sequences by means of extended molecular dynamics simulations. Our results show
that in the absence of DNA, the three protein forms explore a similar essential
conformational space, whereas when bound to the same DNA target sequence of 25
base pairs, they diversify and restrain the subspace explored. In addition, the
differences in the essential subspaces explored by the residues near the
catalytic site for both the bound and unbound forms are discussed in background
of the experimental protein activity.
PMID- 27506596
TI - Enhancing quantum sensing sensitivity by a quantum memory.
AB - In quantum sensing, precision is typically limited by the maximum time interval
over which phase can be accumulated. Memories have been used to enhance this time
interval beyond the coherence lifetime and thus gain precision. Here, we
demonstrate that by using a quantum memory an increased sensitivity can also be
achieved. To this end, we use entanglement in a hybrid spin system comprising a
sensing and a memory qubit associated with a single nitrogen-vacancy centre in
diamond. With the memory we retain the full quantum state even after coherence
decay of the sensor, which enables coherent interaction with distinct weakly
coupled nuclear spin qubits. We benchmark the performance of our hybrid quantum
system against use of the sensing qubit alone by gradually increasing the
entanglement of sensor and memory. We further apply this quantum sensor-memory
pair for high-resolution NMR spectroscopy of single (13)C nuclear spins.
PMID- 27506597
TI - Roadmap for cardiovascular circulation model.
AB - Computational models of many aspects of the mammalian cardiovascular circulation
have been developed. Indeed, along with orthopaedics, this area of physiology is
one that has attracted much interest from engineers, presumably because the
equations governing blood flow in the vascular system are well understood and can
be solved with well-established numerical techniques. Unfortunately, there have
been only a few attempts to create a comprehensive public domain resource for
cardiovascular researchers. In this paper we propose a roadmap for developing an
open source cardiovascular circulation model. The model should be registered to
the musculo-skeletal system. The computational infrastructure for the
cardiovascular model should provide for near real-time computation of blood flow
and pressure in all parts of the body. The model should deal with vascular beds
in all tissues, and the computational infrastructure for the model should provide
links into CellML models of cell function and tissue function. In this work we
review the literature associated with 1D blood flow modelling in the
cardiovascular system, discuss model encoding standards, software and a model
repository. We then describe the coordinate systems used to define the vascular
geometry, derive the equations and discuss the implementation of these coupled
equations in the open source computational software OpenCMISS. Finally, some
preliminary results are presented and plans outlined for the next steps in the
development of the model, the computational software and the graphical user
interface for accessing the model.
PMID- 27506598
TI - Frameshift variant FANCL*c.1096_1099dupATTA is not associated with high breast
cancer risk.
PMID- 27506599
TI - What do I need to know about aminoglycoside antibiotics?
AB - The aminoglycosides are broad-spectrum, bactericidal antibiotics that are
commonly prescribed for children, primarily for infections caused by Gram
negative pathogens. The aminoglycosides include gentamicin, amikacin, tobramycin,
neomycin, and streptomycin. Gentamicin is the most commonly used antibiotic in UK
neonatal units. Aminoglycosides are polar drugs, with poor gastrointestinal
absorption, so intravenous or intramuscular administration is needed. They are
excreted renally. Aminoglycosides are concentration-dependent antibiotics,
meaning that the ratio of the peak concentration to the minimum inhibitory
concentration of the pathogen is the pharmacokinetic-pharmacodynamic index best
linked to their antimicrobial activity and clinical efficacy. However, due to
their narrow therapeutic index, the patient's renal function should be monitored
to avoid toxicity, and therapeutic drug monitoring is often required. Here we
provide a review of aminoglycosides, with a particular focus on gentamicin,
considering their pharmacokinetics and pharmacodynamics, and also practical
issues associated with prescribing these drugs in a paediatric clinical setting.
PMID- 27506601
TI - Altered lipid metabolism in Drosophila model of Huntington's disease.
AB - Huntington's disease (HD) is late-onset, progressive neurodegenerative disorder
caused by expansion of polyglutamine (polyQ) repeat within Huntingtin (Htt)
protein. In HD patients, energy-related manifestations such as modulation of
weight during entire course of disease with energy deficit at terminal stage have
been reported, however, underlying reason remains elusive till date. Lipids,
carbohydrate and protein constitute a predominant fraction of body's energy
reservoir and perturbation in their homeostasis may influence weight. To discern
role of these energy molecules in weight alteration, we quantified them in an in
vivo transgenic Drosophila model of HD. We document that diseased flies exhibit
change in weight due to an altered lipid metabolism, as evident from considerably
high lipid levels at the time of disease onset followed by a pathologic decline
at end-stage. An alteration in intracellular lipid droplet size suggested altered
cellular lipid turnover. Furthermore, diseased flies displayed substantial
changes in carbohydrate and protein content. Interestingly, alteration in weight
and lipid levels are independent of the feeding pattern in diseased condition and
exhibit weak correlation with insulin-like peptide or adipokinetic hormone
producing cells. We propose that therapeutic intervention aimed at restoring
lipid levels and associated metabolic pathways may improve longevity and quality
of patient's life.
PMID- 27506600
TI - Prevalence of hardcore smoking in the Netherlands between 2001 and 2012: a test
of the hardening hypothesis.
AB - BACKGROUND: Hardcore smokers are smokers who have smoked for many years and who
do not intend to quit smoking. The "hardening hypothesis" states that light
smokers are more likely to quit smoking than heavy smokers (such as hardcore
smokers). Therefore, the prevalence of hardcore smoking among smokers would
increase over time. If this is true, the smoking population would become harder
to reach with tobacco control measures. In this study we tested the hardening
hypothesis. METHODS: We calculated the prevalence of hardcore smoking in the
Netherlands from 2001 to 2012. Smokers were 'hardcore' if they a) smoked every
day, b) smoked on average 15 cigarettes per day or more, c) had not attempted to
quit in the past 12 months, and d) had no intention to quit within 6 months. We
used logistic regression models to test whether the prevalence changed over time.
We also investigated whether trends differed between educational levels. RESULTS:
Among smokers, the prevalence of hardcore smoking decreased from 40.8 % in 2001
to 32.2 % in 2012. In the general population, it decreased from 12.2 to 8.2 %.
Hardcore smokers were significantly lower educated than non-hardcore smokers.
Among the general population, the prevalence of hardcore smoking decreased more
among higher educated people than among lower educated people. CONCLUSIONS: We
found no support for the hardening hypothesis in the Netherlands between 2001 and
2012. Instead, the decrease of hardcore smoking among smokers suggests a
'softening' of the smoking population.
PMID- 27506602
TI - Peripheral brain-derived neurotrophic factor in autism spectrum disorder: a
systematic review and meta-analysis.
AB - Brain-derived neurotrophic factor (BDNF) regulates neuronal survival and growth
and promotes synaptic plasticity. Recently, researchers have begun to explore the
relationship between peripheral BDNF levels and autism spectrum disorder (ASD),
but the findings are inconsistent. We undertook the first systematic review and
meta-analysis of studies examining peripheral BDNF levels in ASD compared with
healthy controls. The PubMed, Embase, and Cochrane Library databases were
searched for studies published before February 2016. Fourteen studies involving
2,707 participants and 1,131 incident cases were included. The meta-analysis
provided evidence of higher peripheral BDNF levels in ASD compared with controls
[standardized mean difference (SMD) = 0.63, 95% confidence interval (95% CI) =
0.18-1.08; P = 0.006]. Subgroup analyses revealed higher BDNF levels in ASD
compared with controls for both serum [SMD = 0.58, 95% CI = 0.11-1.04; P = 0.02]
and plasma [SMD = 1.27, 95% CI = 0.92-1.61; P < 0.001]. Studies of childhood
yielded similar cumulative effect size [SMD = 0.78, 95% CI = 0.31-1.26; P =
0.001], while this was not true for the studies of adulthood [SMD = 0.04, 95% CI
= -1.72-1.80; P = 0.97]. This meta-analysis suggests that peripheral BDNF levels
are a potential biomarker of ASD.
PMID- 27506603
TI - Criteria for assigning laboratory measurands to models for analytical performance
specifications defined in the 1st EFLM Strategic Conference.
AB - This paper, prepared by the EFLM Task and Finish Group on Allocation of
laboratory tests to different models for performance specifications (TFG-DM), is
dealing with criteria for allocating measurands to the different models for
analytical performance specifications (APS) recognized in the 1st EFLM Strategic
Conference Consensus Statement. Model 1, based on the effect of APS on clinical
outcome, is the model of choice for measurands that have a central role in the
decision-making of a specific disease or clinical situation and where cut
off/decision limits are established for either diagnosing, screening or
monitoring. Total cholesterol, glucose, HbA1c, serum albumin and cardiac
troponins represent practical examples. Model 2 is based on components of
biological variation and should be applied to measurands that do not have a
central role in a specific disease or clinical situation, but where the
concentration of the measurand is in a steady state. This is best achieved for
measurands under strict homeostatic control in order to preserve their
concentrations in the body fluid of interest, but it can also be applied to other
measurands that are in a steady state in biological fluids. In this case, it is
expected that the "noise" produced by the measurement procedure will not
significantly alter the signal provided by the concentration of the measurand.
This model especially applies to electrolytes and minerals in blood plasma
(sodium, potassium, chloride, bicarbonate, calcium, magnesium, inorganic
phosphate) and to creatinine, cystatin C, uric acid and total protein in plasma.
Model 3, based on state-of-the-art of the measurement, should be used for all the
measurands that cannot be included in models 1 or 2.
PMID- 27506604
TI - Review of Disintegrants and the Disintegration Phenomena.
AB - Disintegrant is one of the most important components in a typical tablet dosage
form. It is responsible for ensuring the break-up of the tablet matrix upon
ingestion. Disintegrants act by different mechanisms, and a number of factors may
affect their performance. It is important for formulators to understand how
disintegrants function so as to be able to judiciously use disintegrants to
develop optimized formulations. If the formulator is required to implement the
quality by design paradigm while developing a tablet formulation, it would be
important to determine the impact of component ranges and process variations on
tablet performance and of particular importance, tablet disintegration. Thus, a
better understanding of the mechanisms of disintegrants and the tablet
disintegration processes can be critical to product design success. This review
aims to provide an overview of tablet disintegrants and the disintegration
processes with particular focus on the factors affecting the functionalities of
disintegrants. An updated compendium of different techniques employed to evaluate
disintegrant action and measure disintegration time is also provided. The
objective of this review is to assemble the knowledge about disintegrants and the
measurement of tablet disintegratability so that the information provided could
be of help to tablet formulation development.
PMID- 27506605
TI - Molecular epidemiology of drug-resistant Neisseria gonorrhoeae in Russia (Current
Status, 2015).
AB - BACKGROUND: The widespread distribution of Neisseria gonorrhoeae strains that are
resistant to previously used and clinically implemented antibiotics is a
significant global public health problem. In line with WHO standards, the
national Gonococcal Antimicrobial Surveillance Programme (RU-GASP) has been in
existence in Russia since 2004; herein, the current status (2015) is described,
including associations between N. gonorrhoeae antimicrobial susceptibility,
primary genetic resistance determinants and specific strain sequence types.
METHODS: A total of 124 N. gonorrhoeae strains obtained from 9 regions in Russia
in 2015 were examined using N. gonorrhoeae Multi-Antigen Sequence Typing (NG
MAST), an antimicrobial susceptibility test according to European Committee on
Antimicrobial Susceptibility Testing (EUCAST) criteria and an oligonucleotide
microarray for the identification of mutations in the penA, ponA, rpsJ, gyrA and
parC genes responsible for penicillin G, tetracycline, and fluoroquinolone
resistance. Genogroup (G) isolates were evaluated based on their porB and tbpB
sequence types (STs). RESULTS: NG-MAST analysis showed a diversified population
of N. gonorrhoeae in Russia with 58 sequence types, 35 of which were described
for the first time. The STs 807, 1544, 1993, 5714, 9476 and 12531, which were
typical for some Russian Federation regions and several countries of the former
Soviet Union, were represented by five or more isolates. The internationally
widespread ST 1407 was represented by a single strain in the present study.
Division into genogroups facilitated an exploration of the associations between
N. gonorrhoeae sequence type, antimicrobial resistance spectra and genetic
resistance determinant contents. Preliminarily susceptible (G-807, G-12531) and
resistant (G-5714, G-9476) genogroups were revealed. The variability in the most
frequently observed STs and genogroups in each participating region indicated
geographically restricted antimicrobial susceptibility in N. gonorrhoeae
populations. CONCLUSIONS: Resistance or intermediate susceptibility to previously
recommended antimicrobials, such as penicillin G (60.5 %), ciprofloxacin (41.1 %)
and tetracycline (25 %), is common in the N. gonorrhoeae population. Based on
previous reports and current data, ceftriaxone and spectinomycin should be
recommended for first-line empiric antimicrobial monotherapy for gonorrhoea in
Russia.
PMID- 27506606
TI - Impact of Expression of Vimentin and Axl in Breast Cancer.
AB - BACKGROUND: The association between Axl and vimentin protein expression has been
observed in several cell lines. However, the clinical importance of Axl and
vimentin expression in breast cancer have not been fully determined. PATIENTS AND
METHODS: The expressions of Axl and vimentin were evaluated by
immunohistochemistry in a total of 343 patients with invasive ductal carcinoma.
The relationships between expression of Axl and vimentin and clinicopathologic
characteristics and prognosis were analyzed. RESULTS: Axl expression was
classified into high (n = 170) and low (n = 173) expression groups. Axl
expression alone was not associated with any clinicopathologic factor or
prognosis. Coexistence of vimentin-positive and Axl-high expression was observed
in 10.5% (n = 36). Vimentin-positive and Axl-high tumors were associated with
triple-negative breast cancers (P = .0396) and with poor prognosis in terms of
both recurrence-free survival (P = .0126) and overall survival (P = .0005)
compared to the other groups, including vimentin-positive and Axl-low tumors,
vimentin-negative and Axl-high tumors, and vimentin-negative and Axl-low tumors.
Multivariate analysis showed that coexistence of vimentin-positive and Axl-high
expression was an independent poor prognostic factor for recurrence-free survival
(hazard ratio, 2.78; 95% confidence interval, 1.23-5.68; P = .0158) and overall
survival (hazard ratio, 3.72; 95% confidence interval, 1.51-8.47; P = .0059).
CONCLUSION: Coexistence of vimentin-positive and Axl-high expression is a poor
prognostic factor for primary breast cancer. Vimentin and Axl expression might
contribute to the aggressive phenotype in breast cancer.
PMID- 27506607
TI - Characterizing internet health information seeking strategies by socioeconomic
status: a mixed methods approach.
AB - BACKGROUND: The Internet is valuable for those with limited access to health care
services because of its low cost and wealth of information. Our objectives were
to investigate how the Internet is used to obtain health-related information and
how individuals with differing socioeconomic resources navigate it when presented
with a health decision. METHODS: Study participants were recruited from public
settings and social service agencies. Participants listened to one of two
clinical scenarios - consistent with influenza or bacterial meningitis - and then
conducted an Internet search. Screen-capture video software captured the Internet
search. Participant Internet search strategies were analyzed and coded for pre-
and post-Internet search guess at diagnosis and information seeking patterns.
Individuals who did not have a college degree and were recruited from locations
offering social services were categorized as "lower socioeconomic status" (SES);
the remainder was categorized as "higher SES." Participants were 78 Internet
health information seekers, ranging from 21-35 years of age, who experienced
barriers to accessing health care services. RESULTS: Lower-SES individuals were
more likely to use an intuitive, rather than deliberative, approach to Internet
health information seeking. Lower- and higher-SES participants did not differ in
the tendency to make diagnostic guesses based on Internet searches. Lower-SES
participants were more likely than their higher-SES counterparts to narrow the
scope of their search. CONCLUSIONS: Our findings suggest that individuals with
different levels of socioeconomic status vary in the heuristics and search
patterns they rely upon to direct their searches. The influence and use of
credible information in the process of making a decision is associated with
education and prior experiences with healthcare services. Those with limited
resources may be disadvantaged when turning to the Internet to make a health
decision.
PMID- 27506608
TI - Adequacy of initial evaluation of fever in long-term care facilities.
AB - AIM: Febrile residents in long-term care facilities (LTCF) might be inadequately
evaluated by caregivers. The present study aimed to examine the factors
associated with inadequacy of initial fever evaluations by caregivers at night in
LTCF. METHODS: We carried out a cross-sectional study among a convenience sample
of caregivers employed at 11 LTCF in Japan using a vignette-based questionnaire.
The respondents were randomly assigned to one of two scenarios describing a mild
or severe febrile episode in an LTCF resident at night. The respondents' thinking
patterns were classified based on influential factors in their fever evaluation.
Associations between adequacy of evaluation and respondents' characteristics were
evaluated using generalized linear mixed models. RESULTS: A total of 34% of fever
evaluations among caregivers were considered to be inadequate regarding the
necessity for examination by a physician, due in most cases to underestimating
the severity of the fever. Respondents' thinking patterns in fever evaluation
were significantly associated with the adequacy of the evaluation. Caregivers who
placed particular importance on the preferences of residents and families versus
other factors including the resident's febrile condition, were more likely to
make an inadequate evaluation than those who did not. CONCLUSIONS: Our findings
here suggest that eagerness to comply with residents' preference in fever
evaluation could prompt caregivers not to call for an appropriate diagnostic
procedure. Geriatr Gerontol Int 2017; 17: 1294-1299.
PMID- 27506609
TI - The challenge of using intermittent preventive therapy with
sulfadoxine/pyrimethamine among pregnant women in Uganda.
AB - BACKGROUND: The Uganda National Malaria Control Programme recommends the use of
intermittent preventive therapy in pregnancy with sulfadoxine/pyrimethamine (SP)
to prevent malaria, however, there is overwhelming evidence of low uptake of this
intervention. This study, therefore, sought to examine the factors associated
with taking two or more doses of therapy among women who had had the most recent
live birth. METHODS: This was a secondary data analysis of the 2014 Malaria
Indicator Survey dataset. The outcome was the use of two or more doses of SP for
the most recent live birth while independent variables included; age, highest
education attained, residence (rural and urban), use of radio and community
health teams for malaria related messages, knowledge of taking SP and use of
LLINS to prevent malaria, household wealth, skilled attendant seen at ANC and
number of children the woman has. RESULTS: Of the 1820 women included in the
final analysis, 822 (45.16 %) women took two or more doses of SP. Women who knew
that this therapy was used to prevent malaria and those who had been seen by a
skilled attendant were 10.72 times [Adjusted OR (95 % CI): 10.72 (7.62-15.08), p
value = 0.001] and 3.19 times [Adjusted OR (95 % CI): 3.19 (1.26-8.07), p-value
= 0.015] more likely to take at least two doses as compared to those who did not
know about this therapy and those seen by unskilled attendants, respectively.
CONCLUSION: This study shows that knowledge among women that SP is a medication
used for malaria prevention during pregnancy increases the uptake of two or more
doses of this therapy among pregnant women. This highlights the importance of
behaviour change communication focused on IPTp uptake that can be complemented by
having skilled personnel attending to pregnant women at the antenatal clinic.
PMID- 27506610
TI - Angiomatous pleomorphic xanthoastrocytoma: a case report and literature review.
AB - BACKGROUND: Pleomorphic xanthoastrocytoma is rare, accounting for <1 % of all
central nervous system (CNS) neoplasms. Angiomatous pleomorphic xanthoastrocytoma
is an extremely rare variant of pleomorphic xanthoastrocytoma, with only six
cases reported thus far. CASE PRESENTATION: A 24-year-old Chinese female patient
who presented with seizure and loss of consciousness for 15 min underwent
computed tomography and magnetic resonance imaging, which revealed a mass in the
left parietal lobe. Histologically, the tumor was characterized by pleomorphic
tumor cells and prominent vascularity. The angiomatous region varied, ranging
from a sinusoidal pattern to a venous malformation. Focal fibrinoid necrosis,
hyalinization, and a moderate infiltration by lymphocytes and plasma cells were
visible in the vessel wall. The tumor cells were in close proximity with adjacent
small vessels. Capillaries adjacent to or extending between tumor cells were
focally observed. Most tumor cells were positive for glial fibrillary acidic
protein and oligodendrocyte lineage transcription factor 2. The Ki-67 index was
low. Based on the patient's history, clinical data, and pathological findings,
she was diagnosed with angiomatous pleomorphic xanthoastrocytoma (WHO grade II).
CONCLUSIONS: This case serves as a reminder to pathologists of the need to be
aware of this rare variant of pleomorphic xanthoastrocytoma to avoid a
misdiagnosis of this indolent CNS tumor and therefore inappropriate treatment.
PMID- 27506611
TI - A Dynamical Analysis of the Suitability of Prehistoric Spheroids from the Cave of
Hearths as Thrown Projectiles.
AB - Spheroids are ball-shaped stone objects found in African archaeological sites
dating from 1.8 million years ago (Early Stone Age) to at least 70,000 years ago
(Middle Stone Age). Spheroids are either fabricated or naturally shaped stones
selected and transported to places of use making them one of the longest-used
technologies on record. Most hypotheses about their use suggest they were
percussive tools for shaping or grinding other materials. However, their size and
spherical shape make them potentially useful as projectile weapons, a property
that, uniquely, humans have been specialised to exploit for millions of years.
Here we show (using simulations of projectile motions resulting from human
throwing) that 81% of a sample of spheroids from the late Acheulean (Bed 3) at
the Cave of Hearths, South Africa afford being thrown so as to inflict worthwhile
damage to a medium-sized animal over distances up to 25 m. Most of the objects
have weights that produce optimal levels of damage from throwing, rather than
simply being as heavy as possible (as would suit other functions). Our results
show that these objects were eminently suitable for throwing, and demonstrate how
empirical research on behavioural tasks can inform and constrain our theories
about prehistoric artefacts.
PMID- 27506612
TI - Curative hepatitis C treatment is effective in drug users, trial shows.
PMID- 27506613
TI - Prevalence and antimicrobial susceptibility pattern of methicillin resistant
Staphylococcus aureus isolated from clinical samples at Yekatit 12 Hospital
Medical College, Addis Ababa, Ethiopia.
AB - BACKGROUND: Staphylococcus aureus particularly MRSA strains are one of the major
causes of community and hospital acquired bacterial infections. They are also
becoming increasingly multi-drug resistant and have recently developed resistance
to vancomycin, which has been used successfully to treat MRSA for many years. In
vitro determination of drug resistance patterns of S. aureus is critical for the
selection of effective drugs for the treatment of staphylococci infections. The
main aim of this study was to determine the prevalence of methicillin resistant
S. aureus strains from different clinical specimens from patients referred for
routine culture and sensitivity testing. METHOD: A cross sectional study was
conducted among 1360 participants at Yekatit 12 Hospital Medical College in
Ethiopia from September 2013 to April 2014. Clinical samples from various
anatomical sites of study participants were cultured on blood agar and mannitol
salt agar and identified to be S. aureus by using catalase, coagulase and DNAse
tests. S. aureus isolates then were screened for MRSA using 30 MUg cefoxitin disc
and other 11 antimicrobial drugs by disc diffusion procedure, and agar dilution
and E tests for vancomycin. All S. aureus isolates examined for beta-lactamase
production by employing nitrocefin. Data were analyzed using SPSS version 20
software and logistic regressions were applied to assess any association between
dependent and independent variables. RESULTS: Of 1360 clinical specimens analyzed
S. aureus was recovered from (194, 14.3 %). Rate of isolation of S. aureus with
regard to clinical specimens was the highest in pus (118, 55.4 %).No S. aureus
was isolated from CSF and urethral discharge. Out of 194 S. aureus isolates, (34,
17.5 %) were found out to be MRSA and the remaining (160, 82.5 %) were MSSA.
Ninety eight (50.5 %) S. aureus were multi drug resistant and the highest
isolates were resistant to penicillin (187, 96.4 %) and least resistant for
clindamycin (23, 11.9 %) and vancomycin (10, 5.1 %). MRSA strains were 100 %
resistant to penicillin G, erythromycin, trimethoprim-sulfamethoxazole and least
resistant to vancomycin (10, 29.4 %). Out of 194 S. aureus isolates (153, 79.0 %)
were beta-lactamase producers. CONCLUSION: In this study S. aureus isolates
exhibited very high degree of resistance to different antibiotics. The isolates
were also multidrug resistant to several combinations of the tested antibiotics.
The emergence of vancomycin resistant S. aureus highlights the value of prudent
prescribing of antibiotics and avoiding their irrational use.
PMID- 27506614
TI - Overexpression of diacylglycerol acyltransferase in Yarrowia lipolytica affects
lipid body size, number and distribution.
AB - In the oleaginous yeast Yarrowia lipolytica, the diacylglycerol acyltransferases
(DGATs) are major factors for triacylglycerol (TAG) synthesis. The Q4 strain, in
which the four acyltransferases have been deleted, is unable to accumulate lipids
and to form lipid bodies (LBs). However, the expression of a single
acyltransferase in this strain restores TAG accumulation and LB formation. Using
this system, it becomes possible to characterize the activity and specificity of
an individual DGAT. Here, we examined the effects of DGAT overexpression on lipid
accumulation and LB formation in Y. lipolytica Specifically, we evaluated the
consequences of introducing one or two copies of the Y. lipolytica DGAT genes
YlDGA1 and YlDGA2 Overall, multi-copy DGAT overexpression increased the lipid
content of yeast cells. However, the size and distribution of LBs depended on the
specific DGAT overexpressed. YlDGA2 overexpression caused the formation of large
LBs, while YlDGA1 overexpression generated smaller but more numerous LBs. This
phenotype was accentuated through the addition of a second copy of the
overexpressed gene and might be linked to the distinct subcellular localization
of each DGAT, i.e. YlDga1 being localized in LBs, while YlDga2 being localized in
a structure strongly resembling the endoplasmic reticulum.
PMID- 27506616
TI - Factors Associated With Gastrostomy Tube Removal in Patients With Dysphagia After
Stroke.
AB - Gastrostomy feeding tubes are commonly placed in patients with dysphagia after
stroke. The subsequent removal of the tube is a primary goal during
rehabilitation. The purpose of our review was to identify predictors and factors
associated with gastrostomy tube removal in patients with dysphagia after stroke.
We conducted a literature review following the PRISMA statement and included the
search databases PubMed, Scopus, Web of Science, and CINAHL. Articles were
included in the final analysis per predefined inclusion and exclusion criteria.
Our search retrieved a total of 853 results consisting of 416 articles (after
eliminating duplicates). Six articles met our final eligibility criteria. The
following factors were identified in at least 1 article as being significantly
associated with gastrostomy tube removal: reduced age, decreased number of
comorbidities, prolonged inpatient rehabilitation stay, absence of bilateral
stroke, nonhemorrhagic stroke, reduced dysphagia severity, absence of aspiration,
absence of premature bolus loss, and timely initiation of pharyngeal swallow.
Aspiration was the only factor that was investigated by 2 studies-both using
multiple regression and both showing stable results, with absence of aspiration
increasing the chances for tube removal. In conclusion, little is known about
factors associated with gastrostomy tube removal in patients with dysphagia after
stroke. Most of the identified factors are associated with stroke or disease
severity; however, the role of the individual factors remains unclear. The
strongest predictor appears to be absence of aspiration on modified barium
swallow studies emphasizing the importance of instrumental swallow studies in
this patient population.
PMID- 27506617
TI - Microscopic mechanistic study on the multiferroic of R2CoMnO6/La2CoMnO6 (R = Ce,
Pr, Nd, Pm, Sm, Gd, Tb, Dy, Ho, Er, Tm) by chemical and hydrostatic pressures: a
first-principles calculation.
AB - A specific class of multiferroic superlattices R2CoMnO6/La2CoMnO6 (R = Ce, Pr,
Nd, Pm, Sm, Gd, Tb, Dy, Ho, Er, Tm), which displayed observable electric
polarizations and considerable magnetization, were investigated based on density
functional theory. The multiferroic behavior was induced by both of the a(-)a(
)c(+) Glazer rotation patterns of BO6 (CoO6 and MnO6) octahedra and ferromagnetic
coupling in the magnetic ordered superlattices. In addition, the ferroelectric
and ferromagnetic properties of R2CoMnO6/La2CoMnO6 superlattices can be tuned by
chemical pressure and hydrostatic pressure, with the former being more effective
in tuning magnetoelectric properties than the latter. For chemical pressure, the
incorporation of lanthanide ions promoted an increase of BO6 octahedral tilting,
reflected by the sharp decrease of Co-O3-Mn bond angles in the R-layer along the
c axis. By contrast, the hydrostatic pressure acts on all three directions of the
superlattice so that the change in Co-O-Mn bond angles is relatively small,
therefore the octahedral distortion is much smaller than that caused by chemical
pressure. Consequently, the electric polarization and magnetization changed more
slowly. Our first-principles simulations proposed a series of rational
multiferroic superlattices with tunable ferromagnetism and ferroelectricity by
chemical and hydrostatic pressures, with expectation to be applied as novel
spintronic materials.
PMID- 27506615
TI - Transcriptomic evidence for modulation of host inflammatory responses during
febrile Plasmodium falciparum malaria.
AB - Identifying molecular predictors and mechanisms of malaria disease is important
for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic
studies in humans have so far been limited to retrospective analysis of blood
samples from clinical cases. In this prospective, proof-of-principle study, we
compared whole-blood RNA-seq profiles at pre-and post-infection time points from
Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during
their first seasonal PCR-positive P. falciparum infection with those from malaria
naive Dutch adults after a single controlled human malaria infection (n = 5). Our
data show a graded activation of pathways downstream of pro-inflammatory
cytokines, with the highest activation in malaria-naive Dutch individuals and
significantly reduced activation in malaria-experienced Malians. Newly febrile
and asymptomatic infections in Malians were statistically indistinguishable
except for genes activated by pro-inflammatory cytokines. The combined data
provide a molecular basis for the development of a pyrogenic threshold as
individuals acquire immunity to clinical malaria.
PMID- 27506618
TI - Nuclear receptors as pharmacological targets, where are we now?
AB - Knowledge of integrative physiology is a major challenge for scientists, as even
small deregulation could lead to diseases. Cells communicate with each other to
control many processes such as growth, migration, survival, or differentiation.
Such interaction could be achieved via several mechanisms either through cell
cell interactions and/or through the signaling of molecules that bind to
receptors on the membrane or in the target cells. The produced molecules could
have either autocrine, paracrine stimulations, or even act on distant organs
(endocrine signaling).
PMID- 27506619
TI - CDK5 downregulation enhances synaptic plasticity.
AB - CDK5 is a serine/threonine kinase that is involved in the normal function of the
adult brain and plays a role in neurotransmission and synaptic plasticity.
However, its over-regulation has been associated with Tau hyperphosphorylation
and cognitive deficits. Our previous studies have demonstrated that CDK5
targeting using shRNA-miR provides neuroprotection and prevents cognitive
deficits. Dendritic spine morphogenesis and forms of long-term synaptic
plasticity-such as long-term potentiation (LTP)-have been proposed as essential
processes of neuroplasticity. However, whether CDK5 participates in these
processes remains controversial and depends on the experimental model. Using wild
type mice that received injections of CDK5 shRNA-miR in CA1 showed an increased
LTP and recovered the PPF in deficient LTP of APPswe/PS1Delta9 transgenic mice.
On mature hippocampal neurons CDK5, shRNA-miR for 12 days induced increased
dendritic protrusion morphogenesis, which was dependent on Rac activity. In
addition, silencing of CDK5 increased BDNF expression, temporarily increased
phosphorylation of CaMKII, ERK, and CREB; and facilitated calcium signaling in
neurites. Together, our data suggest that CDK5 downregulation induces synaptic
plasticity in mature neurons involving Ca2+ signaling and BDNF/CREB activation.
PMID- 27506622
TI - Erratum to: Outcome and prognosis of hypoxic brain damage patients undergoing
neurological early rehabilitation.
PMID- 27506620
TI - Cell-cell junctional mechanotransduction in endothelial remodeling.
AB - The vasculature is one of the most dynamic tissues that encounter numerous
mechanical cues derived from pulsatile blood flow, blood pressure, activity of
smooth muscle cells in the vessel wall, and transmigration of immune cells. The
inner layer of blood and lymphatic vessels is covered by the endothelium, a
monolayer of cells which separates blood from tissue, an important function that
it fulfills even under the dynamic circumstances of the vascular
microenvironment. In addition, remodeling of the endothelial barrier during
angiogenesis and trafficking of immune cells is achieved by specific modulation
of cell-cell adhesion structures between the endothelial cells. In recent years,
there have been many new discoveries in the field of cellular mechanotransduction
which controls the formation and destabilization of the vascular barrier. Force
induced adaptation at endothelial cell-cell adhesion structures is a crucial node
in these processes that challenge the vascular barrier. One of the key examples
of a force-induced molecular event is the recruitment of vinculin to the VE
cadherin complex upon pulling forces at cell-cell junctions. Here, we highlight
recent advances in the current understanding of mechanotransduction responses at,
and derived from, endothelial cell-cell junctions. We further discuss their
importance for vascular barrier function and remodeling in development,
inflammation, and vascular disease.
PMID- 27506621
TI - Chromosome doubling to overcome the chrysanthemum cross barrier based on insight
from transcriptomic and proteomic analyses.
AB - BACKGROUND: Cross breeding is the most commonly used method in chrysanthemum
(Chrysanthemum morifolium) breeding; however, cross barriers always exist in
these combinations. Many studies have shown that paternal chromosome doubling can
often overcome hybridization barriers during cross breeding, although the
underlying mechanism has seldom been investigated. RESULTS: In this study, we
performed two crosses: C. morifolium (pollen receptor) * diploid C. nankingense
(pollen donor) and C. morifolium * tetraploid C. nankingense. Seeds were obtained
only from the latter cross. RNA-Seq and isobaric tags for relative and absolute
quantitation (iTRAQ) were used to investigate differentially expressed genes and
proteins during key embryo development stages in the latter cross. A previously
performed cross, C. morifolium * diploid C. nankingense, was compared to our
results and revealed that transcription factors (i.e., the agamous-like MADS-box
protein AGL80 and the leucine-rich repeat receptor protein kinase EXS), hormone
responsive genes (auxin-binding protein 1), genes and proteins related to
metabolism (ATP-citrate synthase, citrate synthase and malate dehydrogenase) and
other genes reported to contribute to embryo development (i.e., LEA, elongation
factor and tubulin) had higher expression levels in the C. morifolium *
tetraploid C. nankingense cross. In contrast, genes related to senescence and
cell death were down-regulated in the C. morifolium * tetraploid C. nankingense
cross. CONCLUSIONS: The data resources helped elucidate the gene and protein
expression profiles and identify functional genes during different development
stages. When the chromosomes from the male parent are doubled, the genes
contributing to normal embryo developmentare more abundant. However, genes with
negative functions were suppressed, suggesting that chromosome doubling may
epigenetically inhibit the expression of these genes and allow the embryo to
develop normally.
PMID- 27506623
TI - Cerebral collateral circulation and acute ischaemic stroke.
PMID- 25971898
TI - Prenatal diagnosis of hypophosphatasia congenita using ultrasonography.
AB - Congenital hypophosphatasia is a rare fatal skeletal dysplasia. Antenatal
determinants of lethality include small thoracic circumference with pulmonary
hypoplasia and severe micromelia. These features were present in the fetus of a
25-year-old female who came for an anomaly scan in her second trimester of
pregnancy. Additional findings of generalized demineralization and osteochondral
spurs led to the diagnosis of hypophosphatasia congenita. The pregnancy was
terminated, and the findings were confirmed on autopsy. Common differential
diagnoses with clues to diagnose the above mentioned condition have been
discussed here. Early and accurate detection of this medical condition is
important as no treatment has been established for this condition. Therefore,
antenatal ultrasonography helps in diagnosing and decision making with respect to
the current pregnancy and lays the foundation for the genetic counseling of the
couple.
PMID- 27506626
TI - Taming contact line instability for pattern formation.
AB - Coating surfaces with different fluids is prone to instability producing
inhomogeneous films and patterns. The contact line between the coating fluid and
the surface to be coated is host to different instabilities, limiting the use of
a variety of coating techniques. Here we take advantage of the instability of a
receding contact line towards cusp and droplet formation to produce linear
patterns of variable spacings. We stabilize the instability of the cusps towards
droplet formation by using polymer solutions that inhibit this secondary
instability and give rise to long slender cylindrical filaments. We vary the
speed of deposition to change the spacing between these filaments. The
combination of the two gives rise to linear patterns into which different
colloidal particles can be embedded, long DNA molecules can be stretched and
particles filtered by size. The technique is therefore suitable to prepare
anisotropic structures with variable properties.
PMID- 27506627
TI - What makes intersectoral partnerships for health promotion work? A review of the
international literature.
AB - A Health in All Policies approach requires creating and sustaining intersectoral
partnerships for promoting population health. This scoping review of the
international literature on partnership functioning provides a narrative
synthesis of findings related to processes that support and inhibit health
promotion partnership functioning. Searching a range of databases, the review
includes 26 studies employing quantitative (n = 8), qualitative (n = 10) and
mixed method (n = 8) designs examining partnership processes published from
January 2007 to June 2015. Using the Bergen Model of Collaborative Functioning as
a theoretical framework for analyzing the findings, nine core elements were
identified that constitute positive partnership processes that can inform best
practices: (i) develop a shared mission aligned to the partners' individual or
institutional goals; (ii) include a broad range of participation from diverse
partners and a balance of human and financial resources; (iii) incorporate
leadership that inspires trust, confidence and inclusiveness; (iv) monitor how
communication is perceived by partners and adjust accordingly; (v) balance formal
and informal roles/structures depending upon mission; (vi) build trust between
partners from the beginning and for the duration of the partnership; (vii) ensure
balance between maintenance and production activities; (viii) consider the impact
of political, economic, cultural, social and organizational contexts; and (ix)
evaluate partnerships for continuous improvement. Future research is needed to
examine the relationship between these processes and how they impact the longer
term outcomes of intersectoral partnerships.
PMID- 27506628
TI - Difference in DNA-binding abilities of Fur-homolog DNA binding protein from
Neisseria gonorrhoeae.
AB - Gonorrhea is a severe disease infecting both men and women worldwide. The
causative agent of the disease is Neisseria gonorrhoeae. The organism mostly
affects human beings in iron restricted environments. In such an environment the
organism produces a set of proteins which are mostly absent in iron rich
environments. The expressions of the genes for the proteins are regulated by the
transcription factor (TF) belonging to the Fur family. Interestingly, the same TF
acts as the activator and repressor of genes. In this present work, an attempt
has been made to analyze the molecular details of the differential DNA-binding
activities of the TF from Neisseria gonorrhoeae to come up with a plausible
molecular reason behind the difference DNA binding activities of the same TF.
Computational modelling technique was used to build the three dimensional
structure of the TF. Molecular docking and molecular dynamics simulations were
employed to determine the binding interactions between the TF and the promoter
DNA. With the help of the computational techniques, the biochemical reason behind
the different modes of DNA binding by the TF was analyzed. Results from this
analysis may be useful to future drug development endeavours to curtail the
spread of Gonorrhea.
PMID- 27506629
TI - NaGd(MoO4)2 nanocrystals with diverse morphologies: controlled synthesis, growth
mechanism, photoluminescence and thermometric properties.
AB - Pure tetragonal phase, uniform and well-crystallized sodium gadolinium molybdate
(NaGd(MoO4)2) nanocrystals with diverse morphologies, e.g. nanocylinders,
nanocubes and square nanoplates have been selectively synthesized via oleic acid
mediated hydrothermal method. The phase, structure, morphology and composition of
the as-synthesized products are studied. Contents of both sodium molybdate and
oleic acid of the precursor solutions are found to affect the morphologies of the
products significantly, and oleic acid plays a key role in the morphology
controlled synthesis of NaGd(MoO4)2 nanocrystals with diverse morphologies.
Growth mechanism of NaGd(MoO4)2 nanocrystals is proposed based on time-dependent
morphology evolution and X-ray diffraction analysis. Morphology-dependent down
shifting photoluminescence properties of NaGd(MoO4)2: Eu(3+) nanocrystals, and
upconversion photoluminescence properties of NaGd(MoO4)2: Yb(3+)/Er(3+) and
Yb(3+)/Tm(3+) nanoplates are investigated in detail. Charge transfer band in the
down-shifting excitation spectra shows a slight blue-shift, and the luminescence
intensities and lifetimes of Eu(3+) are decreased gradually with the morphology
of the nanocrystals varying from nanocubes to thin square nanoplates.
Upconversion energy transfer mechanisms of NaGd(MoO4)2: Yb(3+)/Er(3+),
Yb(3+)/Tm(3+) nanoplates are proposed based on the energy level scheme and power
dependence of upconversion emissions. Thermometric properties of NaGd(MoO4)2:
Yb(3+)/Er(3+) nanoplates are investigated, and the maximum sensitivity is
determined to be 0.01333 K(-1) at 285 K.
PMID- 27506630
TI - Effects of yuja peel extract and its flavanones on osteopenia in ovariectomized
rats and osteoblast differentiation.
AB - SCOPE: Yuja (Citrus junos Tanaka) possesses various health benefits, but its
effects on bone health are unknown. In this study, the preventative effects of
yuja peel ethanol extract (YPEE) on osteopenia were determined in ovariectomized
(OVX) rats, and the mechanisms by which YPEE and its flavanones regulate
osteoblastogenesis were examined in vitro. METHODS AND RESULTS: The effects of
YPEE on osteoblastogenesis were investigated in MC3T3-E1 cells. YPEE promoted
alkaline phosphatase (ALP) activity, mineralization, and the expression of
osteoblast differentiation marker genes, such as ALP, runt-related transcription
factor 2 (Runx2), and osteocalcin. YPEE and its flavanones promoted osteoblast
differentiation via BMP-2-mediated p38 and the Smad1/5/8 signaling pathway. YPEE
supplementation significantly decreased body weight and increased uterine weight
and bone mineral density in OVX rats. Based on a micro-CT analysis of femurs,
YPEE significantly attenuated osteopenia and increased trabecular volume
fraction, trabecular separation, and trabecular number (p < 0.05). CONCLUSION:
Dietary YPEE has a protective effect on OVX-induced osteopenia. YPEE and its
flavanones promote osteoblastogenesis via the activation of the
BMP/p38/Smad/Runx2 pathways. These results extend our knowledge of the beneficial
effects of YPEE and provide a basis for the development of novel therapies for
osteoporosis.
PMID- 27506631
TI - Characterization of complex, heterogeneous lipid A samples using HPLC-MS/MS
technique I. Overall analysis with respect to acylation, phosphorylation and
isobaric distribution.
AB - We established a new reversed phase-high performance liquid chromatography method
combined with electrospray ionization quadrupole time-of-flight tandem mass
spectrometry for the simultaneous determination and structural characterization
of different lipid A types in bacteria (Escherichia coli O111, Salmonella
adelaide O35 and Proteus morganii O34) showing serological cross-reactivity. The
complex lipid A mixtures (obtained by simple extraction and acid hydrolysis of
the outer membrane lipopolysaccharides) were separated and detected without
phosphate derivatization. Several previously unidentified ions were detected,
which differed in the number and type of acyl chains and number of phosphate
groups. In several cases, we observed the different retention of isobaric lipid A
species, which had different secondary fatty acyl distribution at the C2' or the
C3' sites. The fragmentation of the various, C4' monophosphorylated lipid A
species in deprotonated forms provided structural assignment for each component.
Fragmentation pathways of the tri-acylated, tetra-acylated, penta-acylated, hexa
acylated and hepta-acylated lipid A components and of the lipid A partial
structures are suggested. As standards, the hexa-acylated ion at m/z 1716 with
the E. coli-type acyl distribution and the hepta-acylated ion at m/z 1954 with
the Salmonella-type acyl distribution were used. The results confirmed the
presence of multiple forms of lipid A in all strains analyzed. In addition, the
negative-ion mode MS permitted efficient detection for non-phosphorylated lipid A
components, too. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27506632
TI - Epileptic spasms in epilepsy with myoclonic-atonic seizures (Doose syndrome).
AB - AIM: To describe the occurrence of epileptic spasms in epilepsy with myoclonic
atonic seizures (EMAS) or Doose syndrome. METHODS: Case descriptions of patients
with EMAS and epileptic spasms. Diagnosis of EMAS was performed according to the
following criteria: (1) onset of myoclonic, myoclonic-atonic, or atonic seizures
at between 7 months and 6 years of age; (2) normal development before onset of
epilepsy; (3) absence of structural cerebral abnormalities on MRI; (4) presence
of generalized spike-waves or polyspike-waves on EEG; and (5) exclusion of other
myoclonic epilepsies. RESULTS: Four patients with EMAS were included. For each of
them, epileptic spasms were documented by video interpretation, or video-EEG when
available. CONCLUSIONS: Our description of epileptic spasms in four patients with
EMAS enlarges the spectrum of seizures that may be observed in this syndrome, as
well as the number of epilepsy syndromes which may involve epileptic spasms. This
evidence suggests that the presence of epileptic spasms is consistent with a
diagnosis of EMAS; epileptic spasms should therefore not be considered a seizure
type that excludes diagnosis of this epilepsy syndrome. The prognostic
significance of epileptic spasms associated with EMAS remains unknown.
PMID- 27506633
TI - A 6-month, randomized, double-blind, placebo-controlled study evaluating the
ability of a marine complex supplement to promote hair growth in men with
thinning hair.
AB - BACKGROUND: Male pattern baldness, or androgenetic alopecia, affects
approximately 50% of the adult population and can cause poor self-image, low self
esteem and have a significant negative impact on the quality of life. An oral
nutraceutical supplement based on a marine complex formulation has previously
been reported to significantly increase the number of terminal hairs in women
with thinning hair. AIMS: The objective of this double-blind, placebo-controlled
study was to confirm the beneficial effects of a similar marine complex
supplement in adult male subjects with thinning hair (Viviscal(r) Man;
Lifes2good, Inc., Chicago, IL, USA). PATIENTS/METHODS: Healthy adult male
subjects with thinning hair associated with clinically diagnosed male pattern
hair loss were enrolled and randomized to receive study drug or placebo twice
daily. RESULTS: At Day 90, subjects indicated a significant improvement in three
of six quality of life measures as well as a significant overall improvement in
quality of life. After 180 days, significant increases were observed for total
hair count, total hair density, and terminal hair density (for each, P = 0.001).
The investigator assessments revealed significant improvements in terminal and
vellus hair count and terminal hair density. Hair pull test results were
significantly lower (fewer hairs removed) for study drug vs. placebo at Days 90
(P < 0.05) and 180 (P < 0.01). There were no reports of treatment-emergent
adverse events. CONCLUSION: The results of this study showed for the first time
that a dietary supplement containing a marine complex and other ingredients can
decrease hair shedding and promote hair growth in men with thinning hair.
PMID- 27506634
TI - High density genome wide genotyping-by-sequencing and association identifies
common and low frequency SNPs, and novel candidate genes influencing cow milk
traits.
AB - High-throughput sequencing technologies have increased the ability to detect
sequence variations for complex trait improvement. A high throughput genome wide
genotyping-by-sequencing (GBS) method was used to generate 515,787 single
nucleotide polymorphisms (SNPs), from which 76,355 SNPs with call rates >85% and
minor allele frequency >=1.5% were used in genome wide association study (GWAS)
of 44 milk traits in 1,246 Canadian Holstein cows. GWAS was accomplished with a
mixed linear model procedure implementing the additive and dominant models. A
strong signal within the centromeric region of bovine chromosome 14 was
associated with test day fat percentage. Several SNPs were associated with
eicosapentaenoic acid, docosapentaenoic acid, arachidonic acid, CLA:9c11t and
gamma linolenic acid. Most of the significant SNPs for 44 traits studied are
novel and located in intergenic regions or introns of genes. Novel potential
candidate genes for milk traits or mammary gland functions include ERCC6, TONSL,
NPAS2, ACER3, ITGB4, GGT6, ACOX3, MECR, ADAM12, ACHE, LRRC14, FUK, NPRL3, EVL,
SLCO3A1, PSMA4, FTO, ADCK5, PP1R16A and TEP1. Our study further demonstrates the
utility of the GBS approach for identifying population-specific SNPs for use in
improvement of complex dairy traits.
PMID- 27506636
TI - Clinical-pathological features and treatment modalities associated with
recurrence in DCIS and micro-invasive carcinoma: Who to treat more and who to
treat less.
AB - The primary aim in the management of DCIS is the prevention of recurrence and
contralateral tumor. Risk factors for DCIS recurrence and appropriate treatments
are still widely debated. Adjuvant therapies after surgical resection reduce
recurrences and contralateral disease, but these treatments have significant
financial costs, side effects and there is a group of low-risk patients who would
not gain additional benefit. The aim of our analysis was to identify clinical
pathological features and treatment modalities associated with recurrence in DCIS
and microinvasive carcinoma. In the Thomas Jefferson University Cancer Registry
of Philadelphia, we identified 865 patients with DCIS or micro-invasive carcinoma
treated between 2003 and 2013. Associations between recurrence and demographic
factors (age at diagnosis, ethnicity), biological features (ER, PR and HER2) and
treatment modalities (surgery, radiotherapy and endocrine treatment) were
assessed. Our single institution register-based study showed that distribution of
age at diagnosis and biological features did not significantly differ among
ethnic groups. Younger women and micro-invasive carcinoma patients were more
likely to undergo mastectomy, while African Americans were more likely to take
endocrine therapy and undergo radiotherapy. In our sample only ER/PR negative
DCIS were associated with significantly higher recurrence rate. Moreover, we
reported a high rate of HER2 positive recurrences, suggesting that expression of
this oncogene may represent a potential biomarker for DCIS at high risk of
recurrence. To better define the molecular profile of the subgroup at worse
prognosis might help to identify biomarkers predictive of recurrence or second
tumors, identifying patients candidates for more appropriate treatments.
PMID- 27506637
TI - Functions of the basal ganglia-paradox or no paradox?
PMID- 27506635
TI - Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with
primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of
ROsuvastatin and eZEtimibe).
AB - AIM: We aimed to compare the effects of fixed-dose combinations of ezetimibe plus
rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia,
including a subgroup analysis of patients with diabetes mellitus (DM) or
metabolic syndrome (MetS). METHOD: This multicenter eight-week randomized double
blind phase III study evaluated the safety and efficacy of fixed-dose
combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin
alone in patients with primary hypercholesterolemia. Four hundred and seven
patients with primary hypercholesterolemia who required lipid-lowering treatment
according to the ATP III guideline were randomized to one of the following six
treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus
rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg
daily). RESULTS: Fixed-dose combination of ezetimibe plus rosuvastatin
significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels
compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed
dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total
cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%,
respectively. Moreover, the effect of combination treatment on cholesterol levels
was more pronounced in patients with DM or MetS than in non-DM or non-MetS
patients, respectively, whereas the effect of rosuvastatin alone did not differ
between DM vs non-DM or MetS vs non-MetS patients. CONCLUSION: Fixed-dose
combinations of ezetimibe and rosuvastatin provided significantly superior
efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol,
and triglyceride levels. Moreover, the reduction rate was greater in patients
with DM or MetS.
PMID- 27506639
TI - Corrigendum to "The redox-active drug metronidazole and thiol-depleting garlic
compounds act synergistically in the protist parasite Spironucleus vortens" [Mol.
Biochem. Parasitol. 206 (1-2) (2016) 20-28].
PMID- 27506638
TI - Cost-effectiveness of neurostimulation in Parkinson's disease with early motor
complications.
AB - BACKGROUND: Recent research efforts have focused on the effects of deep brain
stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild
to-moderate PD experiencing motor complications. OBJECTIVES: We assessed the cost
utility of subthalamic DBS compared with the best medical treatment for German
patients below the age of 61 with early motor complications of PD. METHODS: We
applied a previously published Markov model that integrated health utilities
based on EuroQoL and direct costs over patients' lifetime adjusted to the German
health care payer perspective (year of costing: 2013). Effectiveness was
evaluated using the Parkinson's Disease Questionnaire 39 summary index. We
performed sensitivity analyses to assess uncertainty. RESULTS: In the base-case
analysis, the incremental cost-utility ratio for STN DBS compared to best medical
treatment was 22,700 Euros per quality-adjusted life year gained. The time to,
and costs for, battery exchange had a major effect on the incremental cost
utility ratios, but never exceeded a threshold of 50,000 Euros per quality
adjusted life year. CONCLUSIONS: Our decision analysis supports the fact that STN
DBS at earlier stages of the disease is cost-effective in patients below the age
of 61 when compared with the best medical treatment in the German health care
system. This finding was supported by detailed sensitivity analyses reporting
robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to
medical therapy with respect to quality of life for patients with early motor
complications, this further analysis has shown its cost-effectiveness. (c) 2016
International Parkinson and Movement Disorder Society.
PMID- 27506640
TI - Indoor tanning: bringing the sun inside?
PMID- 27506641
TI - Gender differences on the interacting effects of marital status and health
insurance on long-term colon cancer survival in California, 1995-2014.
PMID- 27506642
TI - Effects of mimic of manganese superoxide dismutase on 2,4,6-trinitrobenzene
sulfonic acid-induced colitis in rats.
AB - The mimic of manganese superoxide dismutase (MnSODm) has been synthesized and
reported to have anti-inflammatory properties. However, whether MnSODm has anti
inflammatory effects on colitis and any underlying mechanisms are poorly
understood. This study was to investigate therapeutic effects and mechanism of
MnSODm on 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model in
rats. Rats were intragastrically administered MnSODm (10, 20, and 40 mg/kg) per
day for 7 days after colitis was induced by TNBS. After treated with MnSODm, the
colonic macroscopic and microscopic damage scores and colonic weight/length
ratios were significantly decreased compared with colitis model group.
Myeloperoxidase (MPO) activity, malonyldialdehyde (MDA), tumor necrosis factor
alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 levels in colon tissues
were also significantly decreased in MnSODm treatment groups. However, superoxide
dismutase (SOD) activity significantly increased and phosphorylated inhibitory
kappa B-alpha (IkappaBalpha), inhibitor kappa B kinase (IKKalpha/beta), and
nuclear factor-kappa Bp65 (NF-kappaBp65) as well as Toll-like receptor 4 (TLR4)
and myeloid differentiation actor 88 (MyD88) in the colonic mucosa were
significantly inhibited by MnSODm treatment. Thus, MnSODm was protective against
colitis via antioxidant activity and by inhibiting inflammatory mediators by down
regulating TLR4/MyD88/NF-kappaB signaling pathways. These data suggest a
potential therapeutic effect of MnSODm in colitis.
PMID- 27506643
TI - Triply Halide-Bridged Dinuclear Iridium(III) Complexes with Chiral Diphosphine
Ligands as New Easy-to-Handle Iridium Catalysts for Asymmetric Hydrogenation of
Imines and N-Heteroaromatics.
AB - Iridium(III) complexes bearing chiral ligands have proved to be active species in
asymmetric hydrogenation of C=N bonds, though there are only a few iridium(III)
precursors. We prepared triply halide-bridged dinuclear iridium complexes bearing
chiral diphosphine ligands by simple treatment of the iridium(I) precursor,
chiral diphosphine, and aqueous hydrogen halide. The strong advantage of these
dinuclear iridium complexes is that they are air and moisture stable, leading to
easy handling in asymmetric synthesis. The dinuclear iridium complexes exhibited
high catalytic activity toward asymmetric hydrogenation of imines and N
heteroaromatics. Moreover, we demonstrated the application of triply halide
bridged dinuclear ruthenium(II) and rhodium(III) catalyst precursors for the
asymmetric hydrogenation of ketonic substrates and simple olefins, respectively.
PMID- 27506644
TI - Parent and Self-Report Ratings on the Perceived Levels of Social Vulnerability of
Adults with Williams Syndrome.
AB - The current study took a multi-informant approach to compare parent to self
report ratings of social vulnerability of adults with Williams syndrome (WS).
Participants included 102 pairs of adults with WS and their parents. Parents
completed the Social Vulnerability Questionnaire and adults with WS completed an
adapted version of the questionnaire. Parents consistently reported higher levels
of social vulnerability for their son/daughter than the individual with WS
reported, with the exception of emotional abuse. The lower ratings of social
vulnerability by adults with WS, compared to their parents, offer new information
about their insight into their own vulnerability. These findings highlight the
importance of teaching self-awareness as a part of a multi-informant approach to
interventions designed to target social vulnerability.
PMID- 27506646
TI - Editor's perspectives - August 2016.
PMID- 27506645
TI - Supportive Dyadic Coping and Psychological Adaptation in Couples Parenting
Children with Autism Spectrum Disorder: The Role of Relationship Satisfaction.
AB - In couples parenting children with Autism Spectrum Disorder (ASD), the partner
becomes a primary source of support for addressing the additional parenting
demands. The purpose of this study was to examine the associations between
supportive dyadic coping and parental adaptation, and to assess the mediating
role of relationship satisfaction between them. Seventy-six couples parenting
children with ASD participated. Data were gathered through self-report
questionnaires and an Actor-Partner Interdependence Mediation Model was used.
Mothers' and fathers' supportive dyadic coping was related to both their own and
partner's relationship satisfaction and parental adaptation. Findings also
revealed the mediation role of relationship satisfaction, in the association
between supportive dyadic coping and parental adaptation. The implications for
research and clinical practice are discussed.
PMID- 27506647
TI - The "Superior Ledge": a Modification of the Standard Superomedial Pedicle
Reduction Mammoplasty to Accentuate Nipple-Areola Complex Projection.
AB - BACKGROUND: The superomedial pedicle parenchymal excision pattern for reduction
mammaplasty has the benefits of a reproducible breast shape and improved
superomedial fullness, but is limited by a susceptibility to nipple retraction.
The senior author of this paper has formalized the "superior ledge" modification
of the superomedial pedicle technique (SL-SMP) to address these limitations.
OBJECTIVE: To describe the technical details of the SL-SMP breast reduction
technique and to analyze patient outcomes. METHODS: The technique involves only
partial-thickness parenchymal excision superolateral to the pedicle, thereby
leaving a "superior ledge" of parenchyma on top of which the nipple-areola
complex (NAC) rests in a tension-free manner. Postoperative photographs were
recorded; and patient demographics, intraoperative details, complications, and
outcomes were recorded and analyzed. RESULTS: One hundred seven patients
underwent SL-SMP reduction mammaplasty between 2007 and 2013. Complications
included wound-healing complications (9.3 %), infection (2.8 %), seroma (1.9 %),
and hematoma (1.9 %). Mean follow-up was 44.6 months (Range: 17-72), and during
that period no incidence of clinically relevant NAC retraction was noted by
either the patient or surgical team. CONCLUSIONS: Maintenance of a distinct
superior ledge underlying the final position of the NAC is an important
modification to stress, to prevent nipple retraction. Importantly, the height of
the ledge can be personalized for each patient. We feel it is a valuable addition
to the plastic surgeon's armamentarium to optimize outcomes for patients seeking
relief from excessive breast tissue. 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- 27506648
TI - Early life stages of an arctic keystone species (Boreogadus saida) show high
sensitivity to a water-soluble fraction of crude oil.
AB - Increasing anthropogenic activities in the Arctic represent an enhanced threat
for oil pollution in a marine environment that is already at risk from climate
warming. In particular, this applies to species with free-living pelagic larvae
that aggregate in surface waters and under the sea ice where hydrocarbons are
likely to remain for extended periods of time due to low temperatures. We exposed
the positively buoyant eggs of polar cod (Boreogadus saida), an arctic keystone
species, to realistic concentrations of a crude oil water-soluble fraction (WSF),
mimicking exposure of eggs aggregating under the ice to oil WSF leaking from
brine channels following encapsulation in ice. Total hydrocarbon and polycyclic
aromatic hydrocarbon levels were in the ng/L range, with most exposure
concentrations below the limits of detection throughout the experiment for all
treatments. The proportion of viable, free-swimming larvae decreased
significantly with dose and showed increases in the incidence and severity of
spine curvature, yolk sac alterations and a reduction in spine length. These
effects are expected to compromise the motility, feeding capacity, and predator
avoidance during critical early life stages for this important species. Our
results imply that the viability and fitness of polar cod early life stages is
significantly reduced when exposed to extremely low and environmentally realistic
levels of aqueous hydrocarbons, which may have important implications for arctic
food web dynamics and ecosystem functioning.
PMID- 27506649
TI - Oil spills and their impacts on sand beach invertebrate communities: A literature
review.
AB - Sand beaches are highly dynamic habitats that can experience considerable impacts
from oil spills. This review provides a synthesis of the scientific literature on
major oil spills and their impacts on sand beaches, with emphasis on studies
documenting effects and recoveries of intertidal invertebrate communities. One of
the key observations arising from this review is that more attention has
generally been given to studying the impacts of oil spills on invertebrates
(mostly macrobenthos), and not to documenting their biological recovery.
Biological recovery of sand beach invertebrates is highly dynamic, depending on
several factors including site-specific physical properties and processes (e.g.,
sand grain size, beach exposure), the degree of oiling, depth of oil burial, and
biological factors (e.g., species-specific life-history traits). Recovery of
affected communities ranges from several weeks to several years, with longer
recoveries generally associated with physical factors that facilitate oil
persistence, or when cleanup activities are absent on heavily oiled beaches.
There are considerable challenges in quantifying impacts from spills on sand
beach invertebrates because of insufficient baseline information (e.g.,
distribution, abundance and composition), knowledge gaps in their natural
variability (spatial and temporal), and inadequate sampling and replication
during and after oil spills. Thus, environment assessments of impacts and
recovery require a rigorous experimental design that controls for confounding
sources of variability. General recommendations on sampling strategies and
toxicity testing, and a preliminary framework for incorporating species-specific
life history traits into future assessments are also provided.
PMID- 27506650
TI - Partners' Ongoing Treatment for Chronic Disease and the Risk of Psychological
Distress after the Great East Japan Earthquake.
AB - Several studies have reported that not only patients with chronic diseases but
also their partners are likely to face major psychosocial problems. This study
examined the association between a partner's ongoing treatment for chronic
disease and the risk of psychological distress after the Great East Japan
Earthquake (GEJE). In 2012, a questionnaire was distributed as part of a cross
sectional study of participants aged 20 years or older living in a municipality
that had been severely inundated by the tsunami following the GEJE. We identified
couples using the household numbers of the municipality and collected self
reported information on ongoing chronic disease treatment for stroke, cancer,
myocardial infarction, and angina. Psychological distress was evaluated using the
Kessler 6 scale (K6) and was defined as a score >= 5/24 points. Among 1,246
couples (2,492 participants) thus identified, 2,369 completed the K6. The number
of participants whose partners were under treatment for chronic diseases was 209
(9%). Overall, participants with partners who were receiving treatment for
chronic diseases (odds ratio [OR] = 1.3, 95% confidence interval [CI] = 0.95-1.8,
P = 0.09) did not show a significantly higher risk of psychological distress
using logistic regression analysis. Women, but not men, whose partners were
receiving treatment for chronic diseases, had a higher risk of psychological
distress (women: OR = 1.6, P = 0.02; men: OR = 1.0, P = 0.92). After the GEJE,
only in women the presence of partners under treatment for chronic diseases
appears to be a risk factor for psychological distress.
PMID- 27506651
TI - Activation of the trigeminal alpha2-adrenoceptor produces sex-specific, estrogen
dependent thermal antinociception and antihyperalgesia using an operant pain
assay in the rat.
AB - Higher prevalence of several pain disorders in women and sexual dimorphism in G
protein coupled receptor-induced analgesia has been reported. We have previously
shown that alpha2-adrenoceptor-induced antinociception is sex-specific and
attenuated by estrogen in the female rat. However, this evidence was obtained
using reflexive withdrawal-based nociceptive assays conducted on restrained
animals that may not involve cerebral processing. Hence, we evaluated whether
activation of the trigeminal alpha2-adrenoceptor produces sex-specific
antinociceptive and antihyperalgesic effects in the orofacial region of the rat
using a reward conflict-based operant paradigm in which animals must tolerate
nociceptive thermal stimulation to be rewarded. Male and ovariectomized (OVX)
Sprague-Dawley rats were implanted intracisternally with a PE10 cannula for drug
injections. A group of OVX rats (OVX+E) was administered subcutaneously with
estradiol 48h before the test. Effect of clonidine, an alpha2-adrenoceptor
agonist, was determined on the operant pain assay using a fully automated
Orofacial Pain Assessment Device. Number of spout licks, thermode contacts, and
amount of reward intake were automatically recorded by the ANY-maze software.
Using acute pain modeling, clonidine produced a dose-dependent increase in all
three parameters in male and OVX groups, however, it was ineffective in the OVX+E
group. Similarly, using inflammatory pain modeling, clonidine significantly
increased these parameters in carrageenan-treated male and OVX groups but not in
the OVX+E group. Thus, alpha2-adrenoceptor activation produces sex-specific
antinociception and antihyperalgesia and estrogen attenuates these effects in
female rats using an operant pain assay. These findings may help the discovery of
effective analgesics for each sex.
PMID- 27506652
TI - Nicotine evokes kinetic tremor by activating the inferior olive via alpha7
nicotinic acetylcholine receptors.
AB - Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of
movement disorders (e.g., tremor) and epilepsy. Here, we performed behavioral and
immunohistochemical studies using mice and rats to elucidate the mechanisms
underlying nicotine-induced tremor. Treatments of animals with nicotine (0.5
2mg/kg, i.p.) elicited kinetic tremor, which was completely suppressed by the
nACh receptor antagonist mecamylamine (MEC). The specific alpha7 nACh receptor
antagonist methyllycaconitine (MLA) also inhibited nicotine-induced tremor,
whereas the alpha4beta2 nACh antagonist dihydro-beta-erythroidine (DHbetaE) or
the peripheral alpha3beta4 nACh antagonist hexamethonium showed no effects.
Mapping analysis of Fos protein expression, a biological marker of neural
excitation, revealed that a tremorgenic dose (1mg/kg) of nicotine region
specifically elevated Fos expression in the piriform cortex (PirC), medial
habenula, solitary nucleus and inferior olive (IO) among 44 brain regions
examined. In addition, similarly to the tremor responses, nicotine-induced Fos
expression in the PirC and IO was selectively antagonized by MLA, but not by
DHbetaE. Furthermore, an electrical lesioning of the IO, but not the PirC,
significantly suppressed the induction of nicotine tremor. The present results
suggest that nicotine elicits kinetic tremor in rodents by activating the IO
neurons via alpha7 nACh receptors.
PMID- 27506653
TI - Ritanserin-sensitive receptors modulate the prosocial and the anxiolytic effect
of MDMA derivatives, DOB and PMA, in zebrafish.
AB - Little is known about the pharmacological effects of amphetamine derivatives. In
the present study, the effect on social preference and anxiety-like behavior of
2,5-dimetoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine
(PMA), in comparison with 3,4 methylenedioxymethamphetamine (MDMA) was
investigated in zebrafish, an emerging model to study emotional behavior in an
inexpensive and quick manner. DOB (0.05-2mg/kg), PMA (0.0005-2mg/kg) or MDMA
(0.25-20mg/kg), given i.m. to adult zebrafish, progressively increased the time
spent in the proximity of nacre fish picture in a social preference test.
However, high doses were ineffective. Similarly, in the novel tank diving and
light-dark tests the compounds elicited a progressive anxiolytic effect in terms
of time spent in the upper half of the tank and in the light compartment,
respectively. All the above effects were interpolated by symmetrical parabolas.
The 5-HT2A/C antagonist ritanserin (0.025-2.5mg/kg) in association with the
maximal effective dose of MDMA, DOB and PMA blocked both the social and
anxiolytic effect. Taken together these findings demonstrate for the first time
the prosocial and anxiolytic properties of DOB and PMA and focus on the
mechanisms of their action through the serotonergic-like system suggesting a
potential clinical application.
PMID- 27506654
TI - Altered consolidation of extinction-like inhibitory learning in genotype-specific
dysfunctional coping fostered by chronic stress in mice.
AB - Genetic and stress-related factors interact to foster mental disorders, possibly
through dysfunctional learning. In a previous study we reported that a temporary
experience of reduced food availability increases forced swim (FS)-induced
helplessness tested 14days after a first experience in mice of the standard
inbred C57BL/6(B6) strain but reduces it in mice of the genetically unrelated
DBA/2J (D2) strain. Because persistence of FS-induced helplessness influences
adaptive coping with stress challenge and involve learning processes the present
study tested whether the behavioral effects of restricted feeding involved
altered consolidation of FS-related learning. First, we demonstrated that
restricted feeding does not influence behavior expressed on the first FS
experience, supporting a specific effect on persistence rather then development
of helplessness. Second, we found that FS-induced c-fos expression in the
infralimbic cortex (IL) was selectively enhanced in food-restricted (FR) B6 mice
and reduced in FR D2 mice, supporting opposite alterations of consolidation
processes involving this brain area. Third, we demonstrated that immediate post
FS inactivation of IL prevents 24h retention of acquired helplessness by
continuously free-fed mice of both strains, indicating the requirement of a
functioning IL for consolidation of FS-related learning in either mouse strain.
Finally, in line with the known role of IL in consolidation of extinction
memories, we found that restricted feeding selectively facilitated 24h retention
of an acquired extinction in B6 mice whereas impairing it in D2 mice. These
findings support the conclusion that an experience of reduced food availability
strain-specifically affects persistence of newly acquired passive coping
strategies by altering consolidation of extinction-like inhibitory learning.
PMID- 27506656
TI - NMDA antagonist MK 801 in nucleus accumbens core but not shell disrupts the
restraint stress-induced reinstatement of extinguished cocaine-conditioned place
preference in rats.
AB - Relapse is a common feature of cocaine addiction. In rodents, it can be elicited
by cues, stress or the drug. Restraint stress-induced reinstatement of cocaine
conditioned place preference (CPP) is a useful model to study the mechanisms
involved in stress-induced relapse of drug-seeking behavior. There is evidence
that the glutamate NMDA receptors are critically involved in drug- and cue
induced reinstatement of seeking behavior and drug-CPP responses. The aim of this
study was to investigate the contribution of NMDA receptors within core vs. shell
nucleus accumbens (NAc) subregions to restraint stress-induced reinstatement of
extinguished cocaine-CPP. After extinction of cocaine-conditioned preference,
animals were administered MK 801 systemically or directly into intra-core or
intra-shell, and restrained for 30min or left undisturbed in their home-cages.
First, we demonstrated that restraint stress-induced reinstatement of
extinguished cocaine-CPP depends on the duration of restraint as well as on the
context in which it is applied. Second, this effect was blocked by systemic MK
801 administration either before or after restraint. Third, intra-core but not
intra-shell administration abrogated the restraint stress-induced reinstatement.
These findings show that NMDA receptors within NAc core, but not shell, play a
critical role in restraint stress-induced reinstatement of cocaine-CPP.
PMID- 27506655
TI - The role of genes involved in stress, neural plasticity, and brain circuitry in
depressive phenotypes: Convergent findings in a mouse model of neglect.
AB - Early life neglect increases risk for the development of psychopathologies during
childhood and adulthood, including depression and anxiety disorders. We recently
reported epigenetic changes in DNA derived from saliva in three genes predicted
depression in a cohort of maltreated children: DNA-binding protein inhibitor ID-3
(ID3), Glutamate NMDA Receptor (GRIN1), and Tubulin Polymerization Promoting
Protein (TPPP). To validate the role of these genes in depression risk, secondary
analyses were conducted of gene expression data obtained from medial prefrontal
cortex (mPFC) tissue of mice subjected to a model of maternal neglect which
included maternal separation and early weaning (MSEW). Anxiety and depression
like phenotype data derived using the elevated plus maze (EPM) and forced
swimming test (FST), respectively, were also available for secondary analyses.
Behavioral tests were conducted in MSEW and control adult male mice when they
were between 65 and 80days old. ID3, GRIN1 and TPPP gene expression in the mPFC
were found to significantly predict behavioral differences in the EPM and FST.
These results further support the role of these genes in the etiology of
depressive and anxiety phenotypes following early life stress.
PMID- 27506657
TI - Reactive hypoglycaemia with seizure following intraduodenal glucose infusion in a
patient with type 2 diabetes.
PMID- 27506658
TI - Differences in fat accumulation between immature male and female Atlantic salmon
Salmo salar after dietary administration of tetradecylthioacetic acid.
AB - This study provoked sex-specific differences in fat metabolism in Atlantic salmon
Salmo salar, by dietary administration of tetradecylthioacetic acid (TTA) during
their first spring and winter in the sea. The effects of TTA were evaluated in
June of the first spring and May of the second spring in the sea, by analysing
white muscle-fat content. Muscle fat in males and females differed significantly
as a result of TTA in their diet and diet interacted with the sex of the fish.
The fat content during the first spring after dietary TTA was lowered by a
greater amount in females than in males, 3.1-4.3%, respectively (P < 0.05). In
contrast, during the second spring, fat content was lowered by a greater amount
in males than in females, 15.8-16.7%, respectively (P < 0.01). Condition factor
followed a similar pattern to the muscle fat. The results indicate that the
difference in male and female fat accumulation dynamics is related to sex
specific reproduction biology of S. salar. In addition, the findings show that it
is important to consider the sex of the fish and the season of the year when
studying fat dynamics and reproductive biology of S. salar.
PMID- 27506659
TI - Exam preparation course in obstetrics and gynecology for the German Medical State
Examination: proof of concept and implications for the recruitment of future
residents.
AB - OBJECTIVES: Today's written part of the medical state examination requires
students to retrieve a comprehensive amount of knowledge in a limited period of
time. Therefore, the main study objectives were to implement and to evaluate a
two-day exam preparation course for the German Medical State Examination in
obstetrics and gynecology. The project evaluation focused on acceptability,
satisfaction and the gain of knowledge for the participants of such a face-to
face course. STUDY DESIGN: The two-day intensive training for senior medical
students offered a review of the entire exam-relevant content in the field of
obstetrics and gynecology in combination with interactive discussions along
selected exam questions. Skill gains were assessed using pre- and post-course
multiple choice tests. In addition, a qualitative questionnaire assessed
attitudes and satisfaction of course participants. RESULTS: A total of 101 fifth
year senior medical students from Heidelberg University Medical School
participated in the two pilot courses (summer 2014 and winter 2015). Pre- and
post-course tests showed a significant skill-gain from 14.9 to 18.0 points [of a
maximum of 20; pre-post difference 95 % CI (2.21; 3.98), t test: p < 0.001].
Furthermore, the qualitative results showed high satisfaction with the course,
with an average Likert scale grading of 5.63 (2014) and 5.44 (2015) on a scale
from 1 ("extraordinary bad") to 6 ("extraordinary good"). CONCLUSIONS: This study
shows that a two-day intensive course in obstetrics and gynecology is feasible,
effective and highly appreciated by senior medical students preparing for the
Second German Medical State Examination. It further suggests surplus value for
academic clinical departments to recruit future residents. Methods and tools
presented in this paper are intended to inspire and guide clinical colleagues in
implementing the format at their respective universities.
PMID- 27506660
TI - Erratum to: Hard to Believe: Produced by Ken Stone and Irene Silber, 2015, Swoop
Films and Stone Soup Productions (New York, 56 minutes, unrated).
PMID- 27506661
TI - Effects of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and
Neoadjuvant Intraperitoneal/Systemic Chemotherapy on Peritoneal Metastases from
Gastric Cancer.
AB - BACKGROUND: The Peritoneal Cancer Index (PCI) is the most important prognostic
factor following comprehensive treatment for peritoneal metastasis (PM) from
gastric cancer (GCPM); however, 70 % of patients with GCPM showed a PCI score
above the cut-off level at the time of diagnosis. Furthermore, neoadjuvant
chemotherapy may reduce the PCI score to lower than the cut-off levels. In this
study, the effects of neoadjuvant laparoscopic hyperthermic intraperitoneal
chemoperfusion (NLHIPEC) and neoadjuvant intraperitoneal/systemic chemotherapy
(NIPS) were investigated. MATERIALS AND METHODS: In group A, NLHIPEC was
performed twice in 53 patients with GCPM, separated by a 1-month rest interval.
Changes in the PCI were studied at the time of first and second laparoscopy. In
group B, after NLHIPEC, a series of 3-week cycles of NIPS were performed over
three courses in 52 patients. A laparotomy for cytoreductive surgery (CRS) was
then carried out and the PCI changes were studied. RESULTS: In group A, the PCI
score at the time of the second session (11.8 +/- 11.0) was significantly lower
than at the time of the first session (14.2 +/- 10.7), while in group B, the PCI
at the time of laparotomy (9.9 +/- 11.3) was significantly lower than at the time
of NLHIPEC (14.8 +/- 11.4). After NLHIPEC plus NIPS, complete cytoreduction was
achieved in 30 (57.6 %) patients. CONCLUSIONS: NLHIPEC and NIPS are effective
methods of reducing PCI levels before CRS.
PMID- 27506662
TI - Impact of Flap Reconstruction on Radiotoxicity After Salvage Surgery and
Reirradiation for Recurrent Head and Neck Cancer.
AB - BACKGROUND: Recurrent head and neck malignancies remain a therapeutic challenge.
Tissue transfer, in addition to defect coverage and prevention of wound
complications, may potentially decrease radiotoxicity. We evaluated radiation
toxicity and survival outcomes of patients who underwent salvage surgery with
reirradiation, comparing primary closure to flap reconstruction. METHODS:
Retrospective outcomes analysis of recurrent head and neck squamous cell
carcinoma (HNSCC) patients treated with curative intent by salvage surgery (+/-
flap reconstruction) and reirradiation from 1996 to 2011. Recurrent stage,
reirradiation modality, chemotherapy use, and toxicities were evaluated. RESULTS:
Of 96 patients, 59 had primary closure, whereas 37 underwent flap reconstruction
(26 free, 11 pedicled). Median radiation and reirradiation doses were 66 Gy and
60 Gy, respectively. Comparing nonflap and flap patients, there was no
significant difference in acute mild toxicities (100 vs. 100 %, p = 1.0) or acute
severe toxicities (33.9 vs. 37.8 %, p = 0.83). Nonflap patients experienced
significantly greater incidence of both late mild toxicities (81.4 vs. 54.1 %, p
= 0.006) and late severe toxicities (47.5 vs. 21.6 %, p = 0.02). Overall survival
at 5 years was equivalent (33.1 vs. 34.7 %, p = 0.88). Free flap patients had
greater delays to postoperative reirradiation and treatment package times
compared with pedicled flap patients but no meaningful difference in survival
outcomes. CONCLUSIONS: Vascularized tissue potentially helps offset late
toxicities associated with a second radiation course in recurrent head and neck
cancer patients. In these selected patients, flap coverage may confer functional
benefits and improve the long-term radiotoxicity profile.
PMID- 27506663
TI - Pseudoduganella danionis sp. nov., isolated from zebrafish (Danio rerio).
AB - One beige-pigmented, Gram-staining-negative, rod-shaped bacterium, strain E3/2T,
was isolated from a zebrafish, Daniorerio. Phylogenetic analysis based on nearly
full-length 16S rRNA gene sequences showed that the isolate shared 97.7 % 16S
rRNA gene sequence similarity to the species Pseudoduganella violaceinigra and
between 97.4 to 97.0 % to some species of the genera Duganella and Massilia,
including Duganella radicis, Duganella phyllosphaerae, Massilia dura, Massilia
lutea, Duganella sacchari, Duganella zoogloeoides, Massiliaalbidiflava and
Massilia umbonata. Sequence similarities to all other species were below 97 %.
The main cellular fatty acids of the strain were summed feature 3 fatty acids
(C16 : 1omega7c/iso-C15 : 0 2-OH), C10 : 0 3-OH, C16 : 0 and C12 : 0. The
polyamine pattern of strain E3/2T contained predominantly putrescine and 2
hydroxyputrescine. The major quinone was ubiquinone Q-8. Major polar lipids were
diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Based
on phylogenetic, chemotaxonomic, genomic and phenotypic analyses we propose a
novel species of the genus Pseudoduganella named Pseudoduganella danionis sp.
nov., with strain E3/2T (=LMG 29678T=CCM 8698T) as the type strain.
PMID- 27506664
TI - Entanglement revive and information flow within the decoherent environment.
AB - In this paper, the dynamics of entanglement is investigated in the presence of a
noisy environment. We reveal its revival behavior and probe the mechanisms of
this behavior via an information-theoretic approach. By analyzing the correlation
distribution and the information flow within the composite system including the
qubit subsystem and a noisy environment, it has been found that the subsystem
environment coupling can induce the quasi-periodic entanglement revival.
Furthermore, the dynamical relationship among tripartite correlations, bipartite
entanglement and local state information is explored, which provides a new
insight into the non-Markovian mechanisms during the evolution.
PMID- 27506665
TI - Early clinical experience utilizing scintillator with optical fiber (SOF)
detector in clinical boron neutron capture therapy: its issues and solutions.
AB - BACKGROUND: Real-time measurement of thermal neutrons in the tumor region is
essential for proper evaluation of the absorbed dose in boron neutron capture
therapy (BNCT) treatment. The gold wire activation method has been routinely used
to measure the neutron flux distribution in BNCT irradiation, but a real-time
measurement using gold wire is not possible. To overcome this issue, the
scintillator with optical fiber (SOF) detector has been developed. The purpose of
this study is to demonstrate the feasibility of the SOF detector as a real-time
thermal neutron monitor in clinical BNCT treatment and also to report issues in
the use of SOF detectors in clinical practice and their solutions. MATERIAL AND
METHODS: Clinical measurements using the SOF detector were carried out in 16 BNCT
clinical trial patients from December 2002 until end of 2006 at the Japanese
Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute
(KURRI). RESULTS: The SOF detector worked effectively as a real-time thermal
neutron monitor. The neutron fluence obtained by the gold wire activation method
was found to differ from that obtained by the SOF detector. The neutron fluence
obtained by the SOF detector was in better agreement with the expected fluence
than with gold wire activation. The estimation error for the SOF detector was
small in comparison to the gold wire measurement. In addition, real-time
monitoring suggested that the neutron flux distribution and intensity at the
region of interest (ROI) may vary due to the reactor condition, patient motion
and dislocation of the SOF detector. CONCLUSION: Clinical measurements using the
SOF detector to measure thermal neutron flux during BNCT confirmed that SOF
detectors are effective as a real-time thermal neutron monitor. To minimize the
estimation error due to the displacement of the SOF probe during treatment, a
loop-type SOF probe was developed.
PMID- 27506668
TI - Caution is urged over "game changing" asthma drug.
PMID- 27506666
TI - A microdeletion at Xq22.2 implicates a glycine receptor GLRA4 involved in
intellectual disability, behavioral problems and craniofacial anomalies.
AB - BACKGROUND: Among the 21 annotated genes at Xq22.2, PLP1 is the only known gene
involved in Xq22.2 microdeletion and microduplication syndromes with intellectual
disability. Using an atypical microdeletion, which does not encompass PLP1, we
implicate a novel gene GLRA4 involved in intellectual disability, behavioral
problems and craniofacial anomalies. CASE PRESENTATION: We report a female
patient (DGDP084) with a de novo Xq22.2 microdeletion of at least 110 kb
presenting with intellectual disability, motor delay, behavioral problems and
craniofacial anomalies. While her phenotypic features such as cognitive
impairment and motor delay show overlap with Pelizaeus-Merzbacher disease (PMD)
caused by PLP1 mutations at Xq22.2, this gene is not included in our patient's
microdeletion and is not dysregulated by a position effect. Because the
microdeletion encompasses only three genes, GLRA4, MORF4L2 and TCEAL1, we
investigated their expression levels in various tissues by RT-qPCR and found that
all three genes were highly expressed in whole human brain, fetal brain,
cerebellum and hippocampus. When we examined the transcript levels of GLRA4,
MORF4L2 as well as TCEAL1 in DGDP084's family, however, only GLRA4 transcripts
were reduced in the female patient compared to her healthy mother. This suggests
that GLRA4 is the plausible candidate gene for cognitive impairment, behavioral
problems and craniofacial anomalies observed in DGDP084. Importantly, glycine
receptors mediate inhibitory synaptic transmission in the brain stem as well as
the spinal cord, and are known to be involved in syndromic intellectual
disability. CONCLUSION: We hypothesize that GLRA4 is involved in intellectual
disability, behavioral problems and craniofacial anomalies as the second gene
identified for X-linked syndromic intellectual disability at Xq22.2. Additional
point mutations or intragenic deletions of GLRA4 as well as functional studies
are needed to further validate our hypothesis.
PMID- 27506667
TI - Effect of vitamin D3 supplementation on iron status: a randomized, double-blind,
placebo-controlled trial among ethnic minorities living in Norway.
AB - BACKGROUND: Both vitamin D and iron deficiencies are widespread globally, and a
relationship between these deficiencies has been suggested. However, there is a
paucity of randomised controlled trials assessing the effect of vitamin D
supplementation on iron status. PURPOSE: We aimed to investigate whether 16 weeks
of daily vitamin D3 supplementation had an effect on serum ferritin, haemoglobin,
serum iron and transferrin saturation. METHODS: Overall, 251 participants from
South Asia, Middle East and Africa aged 18-50 years who were living in Norway
were randomised to receive daily oral supplementation of 10 MUg vitamin D3, 25
MUg vitamin D3, or placebo for 16 weeks during the late winter. Blood samples
from baseline and after 16 weeks were analysed for serum 25-hydroxyvitamin D (s
25(OH) D), serum ferritin, haemoglobin and serum iron. In total, 214 eligible
participants completed the intervention (86 % of those randomised). Linear
regression analysis were used to test the effect of vitamin D3 supplementation
combined (10 or 25 MUg) and separate doses 10 or 25 MUg compared to placebo on
change (T2-T1) in each outcome variable adjusted for baseline s-25(OH)D values.
RESULTS: There was no difference in change in the levels of s-ferritin (1.9
MUg/L, 95 % CI: -3.2, 7.0), haemoglobin (-0.02 g/dL, 95 % CI: -0.12, 0.09), s
iron (0.4 MUg/L, 95 % CI: -0.5, 1.3) or transferrin saturation (0.7 %, 95 % CI:
0.6.1, 2.0) between those receiving vitamin D3 or those receiving placebo. Serum
25-hydroxyvitamin D increased from 29 nmol/L at baseline to 49 nmol/L after the
intervention, with little change in the placebo group. CONCLUSIONS: In this
population of healthy ethnic minorities from South Asia, the Middle East and
Africa who had low vitamin D status, 16 weeks of daily supplementation with 10 or
25 MUg of vitamin D3 did not significantly affect the haemoglobin levels or other
markers of iron status.
PMID- 27506669
TI - Pretreatment quality-of-life score is a better discriminator of oesophageal
cancer survival than performance status.
AB - OBJECTIVES: Performance status [Eastern Cooperative Oncology Group (ECOG)] is a
physician-assigned score indicating a patient's fitness for treatment. Functional
assessment of cancer therapy-esophagus (FACT-E) is a patient-reported, health
related quality-of-life (HRQOL) instrument containing an oesophageal cancer
subscale (ECS). Our objective was to assess the discriminative ability of
pretreatment FACT-E and ECS when compared with performance status in predicting
survival in patients with Stage II-III oesophageal cancer. METHODS: Patient data
from four prospective studies were pooled together. These four studies included
oesophageal patients who received chemoradiation either as neoadjuvant therapy or
as definitive therapy. Three separate Cox regressions were performed considering
FACT-E, ECS and ECOG as the main predictors, respectively. Receiver-operating
characteristics analyses were performed. RESULTS: Of the 120 curative intent
patients, 39.8% (n = 51), 58.6% (n = 75) and 1.6% (n = 2) had ECOG 0, 1 and 2,
respectively. On Cox regression analysis, pretreatment FACT-E (P = 0.04) and ECS
(P = 0.004) but not ECOG (P = 0.27) were independently associated with overall
survival. ECOG could not discriminate between survivors and non-survivors (P =
0.28) with an area under the curve (AUC) of 0.56 [95% confidence interval (CI):
0.45-0.66], whereas FACT-E (P = 0.02) and ECS (P < 0.001) were discriminative
with AUC = 0.63 (95% CI: 0.52-0.73) and AUC = 0.69 (95% CI: 0.60-0.79),
respectively. CONCLUSIONS: In patients with Stage II-III oesophageal cancer being
considered for curative therapy, pretreatment FACT-E and ECS have better
discrimination for survival than does ECOG. The majority of patients were ECOG
0/1. Thus, these patient-derived scores were able to discriminate survivors from
non-survivors even within this constrained range of clinician-assigned
performance status. This highlights the potential utility of FACT-E and ECS as
prognostic tools.
PMID- 27506671
TI - 'Rare' manifestation of 'rare' disease: sarcoidosis presenting as pancreatitis,
duodenal ulcer and severe acute kidney injury.
PMID- 27506672
TI - Transluminal angioplasty and stenting versus conservative treatment in patients
with symptomatic basilar artery stenosis : Perspective for future clinical
trials.
AB - PURPOSE: Two recent randomized controlled trials (RCT) consistently showed
superiority of aggressive medical treatment versus percutaneous transluminal
angioplasty and stenting (PTAS) in patients with intracranial artery stenosis.
Patients with symptomatic basilar stenosis have a higher long-term risk of
recurrent stroke compared to patients with anterior circulation stenosis but no
study has specifically focused on the role of PTAS in this subgroup. The aim of
our study was to investigate the subgroup of patients with symptomatic basilar
artery stenosis to find evidence for the feasibility of a future clinical trial.
METHODS: Patients with ischemic stroke caused by a symptomatic basilar stenosis
and admitted to five German tertiary care hospitals were included in this
multicenter effectiveness study. Primary outcome was a composite endpoint of
stroke recurrence, clinically relevant restenosis, progression and death. Shared
frailty Cox regression models were used to compare outcome rates between groups.
RESULTS: Of the 139 patients included in the study 79 (57 %) underwent PTAS and
60 (43 %) conservative treatment alone. The median follow-up period was 300 (IQR
18-738) days. Risks of the primary composite outcome (hazard ratio HR 0.49, 95 %
confidence interval CI 0.25-0.97, p = 0.039) and of the key secondary outcomes
recurrent stroke (HR 0.42, 95 % CI 0.19-0.95, p = 0.037) and clinically relevant
restenosis/progression (HR 0.12, 95 % CI 0.03-0.59, p = 0.009) were lower in
patients with PTAS compared to conservative treatment. There was no difference in
all-cause mortality between groups (HR 0.98, 95 % CI 0.19-5.09, p = 0.979).
CONCLUSION: In this retrospective study we could not reproduce the findings from
large RCTs on intracranial stenting. Our data could be considered as a basis for
a prospective study on patient selection for PTAS in the basilar artery.
PMID- 27506673
TI - Transorbital Cavernous Sinus Direct Puncture : Alternative to treat dural
arteriovenous fistula.
AB - INTRODUCTION: The authors present a retrospective series of their clinical
experience in the treatment of cavernous dural arteriovenous fistulas (DAVF) by
direct transorbital puncture of the cavernous sinus as an alternative to the
endovascular approach. METHODS: Between October 2012 and September 2014, eight
patients harboring cavernous DAVF underwent percutaneous treatment by direct
transorbital puncture of the cavernous sinus at three institutions. All patients
presented with ocular symptoms. Standard endovascular approaches, including
transvenous and transarterial routes, were primarily attempted without success in
all cases. Direct puncture was performed through two different approaches, namely
inferolateral and superomedial. The entry point was the inferior and superior
eyelid, respectively. Embolization was performed with coils or Onyx (Covidien,
Irvine, CA). Immediate and late angiographies were used to evaluate the occlusion
of the fistula. RESULTS: Of the patients seven had complete occlusion of the
cavernous DAVFs noted on the immediate and follow-up angiograms and one patient
had residual filling but reduction of the shunt resulted in clinical improvement.
None of the patients had worsening of neurological function. One case was
complicated by inadvertent internal carotid puncture but without clinical
manifestations. One patient experienced postoperative superior ophthalmic vein
thrombosis. CONCLUSION: In very specific cases, when endovascular access is not
possible or fails to occlude cavernous DAVF, direct transorbital puncture of the
cavernous sinus was shown to be feasible, safe and very effective.
PMID- 27506674
TI - Differential expression of skeletal muscle genes following administration of
clenbuterol to exercised horses.
AB - BACKGROUND: Clenbuterol, a beta2-adrenergic receptor agonist, is used
therapeutically to treat respiratory conditions in the horse. However, by virtue
of its mechanism of action it has been suggested that clenbuterol may also have
repartitioning affects in horses and as such the potential to affect performance.
Clenbuterol decreases the percent fat and increases fat-free mass following high
dose administration in combination with intense exercise in horses. In the
current study, microarray analysis and real-time PCR were used to study the
temporal effects of low and high dose chronic clenbuterol administration on
differential gene expression of several skeletal muscle myosin heavy chains,
genes involved in lipid metabolism and the beta2-adrenergic receptor. The effect
of clenbuterol administration on differential gene expression has not been
previously reported in the horse, therefore the primary objective of the current
study was to describe clenbuterol-induced temporal changes in gene expression
following chronic oral administration of clenbuterol at both high and low doses.
RESULTS: Steady state clenbuterol concentrations were achieved at approximately
50 h post administration of the first dose for the low dose regimen and at
approximately 18-19 days (10 days post administration of 3.2 MUg/kg) for the
escalating dosing regimen. Following chronic administration of the low dose (0.8
MUg/kg BID) of clenbuterol, a total of 114 genes were differentially expressed,
however, none of these changes were found to be significant following FDR
adjustment of the p-values. A total of 7,093 genes were differentially expressed
with 3,623 genes up regulated and 3,470 genes down regulated following chronic
high dose administration. Of the genes selected for further study by real-time
PCR, down-regulation of genes encoding myosin heavy chains 2 and 7, steroyl CoA
desaturase and the beta2-adrenergic receptor were noted. For most genes,
expression levels returned towards baseline levels following cessation of drug
administration. CONCLUSION: This study showed no evidence of modified gene
expression following chronic low dose administration of clenbuterol to horses.
However, following chronic administration of high doses of clenbuterol
alterations were noted in transcripts encoding various myosin heavy chains, lipid
metabolizing enzymes and the beta2-adrenergic receptor.
PMID- 27506675
TI - Evaluation of cellular and molecular impact of zearalenone and Escherichia coli
co-exposure on IPEC-1 cells using microarray technology.
AB - BACKGROUND: The gastrointestinal tract is the primary site of toxin interaction,
an interface between the organism and its surroundings. In this study, we
assessed the alteration of intestinal mRNA profile in the case of co-occurrence
of zearalenone (ZEA), a secondary Fusarium metabolite, and Escherichia coli (E.
coli), on the intestinal porcine epithelial cells IPEC-1. We chose this model
since the pig is a species which is susceptible to pathogen and mycotoxin co
exposure. RESULTS: After treating the cells with the two contaminants, either
separately or in combination, the differential gene expression between groups was
assessed, using the microarray technology. Data analysis identified 1691
upregulated and 797 downregulated genes as a response to E. coli exposure, while
for ZEA treated cells, 303 genes were upregulated and 49 downregulated. The co
contamination led to 991 upregulated and 800 downregulated genes. The altered
gene expression pattern was further classified into 8 functional groups. In the
case of co-exposure to ZEA and E.coli, a clear increase of proinflammatory
mechanisms. CONCLUSIONS: These results demonstrate the complex effect of single
or multiple contaminants exposure at cellular and molecular level, with
significant implications that might lead to the activation of pathological
mechanisms. A better understanding of the effects of co-contamination is
mandatory in developing novel exposure regulations and prevention measures.
PMID- 27506676
TI - Follow-up of young patients after acute poisoning by substances of abuse: a
comparative cohort study at an emergency outpatient clinic.
AB - BACKGROUND: Young patients with acute poisoning by substances of abuse have
increased mortality rates in the long term. In Oslo, Norway, most of these
patients are treated at the Oslo Accident and Emergency Outpatient Clinic. The
majority were discharged without follow-up. In 2010, the clinic implemented an
intervention program for patients under the age of 23 presenting with acute
poisoning by substances of abuse. The intervention was a brief motivational
interview with a social worker before discharge, followed by a telephone
consultation. Patients in need of further follow-up were identified and referred.
Our objective was to study short-term effects of the intervention program on
referrals to follow-up and repetition rates of acute poisoning. METHODS:
Comparative cohorts were derived from studies of acute poisoning at the Oslo
Accident and Emergency Outpatient Clinic in 2003, 2008 and 2012. Two age groups
of patients presenting with acute poisoning by substances of abuse were included:
16-22 years and 23-27 years. Patients in the pre-intervention cohorts of 2003 and
2008 were compared with patients of the same age in the post-intervention cohort
of 2012. Repetition rates were estimated using survival analysis. In total, 1323
patients were included; 422 in the younger pre-intervention group, 366 in the
younger post-intervention group, 288 in the older pre-intervention group, and 247
in the older post-intervention group. Overall, the major toxic agents were
ethanol 823/1323 (62 %) and opioids 215/1323 (16 %). 719/1323 (54 %) patients
were male. RESULTS: In the younger groups referrals to follow-up increased from
86/317 (27 %) to 156/366 (43 %) (p < 0.001) after the implementation of the
program. Among the older patients, who were not included in the program, there
was no significant change in referrals. There was no change in the repetition
rate of acute poisoning in either age group. The program established contact with
225/366 (61 %) of the eligible patients. CONCLUSION: More patients were referred
to follow-up after the intervention. We expect this to have a beneficial effect
on their substance use and reduce excess morbidity and mortality in the long
term. There was no change in the repetition rate of poisoning.
PMID- 27506677
TI - Constraint-Induced Aphasia Therapy in the Acute Stage: What Is the Key Factor for
Efficacy? A Randomized Controlled Study.
AB - BACKGROUND: Constraint-induced aphasia therapy (CIAT) has proven effective in
patients with subacute and chronic forms of aphasia. It has remained unclear,
however, whether intensity of therapy or constraint is the relevant factor. Data
about intensive speech and language therapy (SLT) are conflicting. OBJECTIVE: To
identify the effective component of CIAT and assess the feasibility of SLT in the
acute stage after stroke. METHOD: A total of 60 patients with aphasia (68.2 +/-
11.7 years) were enrolled 18.9 days after first-ever stroke. They were randomly
distributed into 3 groups: (1) CIAT group receiving therapy for 3 hours per day
(10 workdays, total 30 hours); (2) conventional communication treatment group,
with same intensity without constraints; and (3) control group receiving
individual therapy twice a day as well as group therapy (total 14 hours).
Patients were assessed pretreatment and posttreatment using the Aachener Aphasia
Test (primary end point: token test) and the Communicative Activity Log (CAL).
RESULTS: Pretreatment, there were no between-group differences. Posttreatment,
all groups showed significant improvements without between-group differences.
CONCLUSION: It was found that 14 hours of aphasia therapy administered within 2
weeks as individual therapy, focusing on individual deficits, combined with group
sessions has proven to be most efficient. This approach yielded the same outcome
as 30 hours of group therapy, either in the form of CIAT or group therapy without
constraints. SLT in an intensive treatment schedule is feasible and was well
tolerated in the acute stage after stroke.
PMID- 27506678
TI - Perceptions of diet, physical activity, and obesity-related health among black
daughter-mother pairs in Soweto, South Africa: a qualitative study.
AB - BACKGROUND: The prevalence of overweight and obesity is on the rise in South
Africa, particularly among females living in urban environments. The purpose of
this qualitative study was to explore the emic perspectives of black young adult
daughter and mother pairs living in Soweto, South Africa on diet, physical
activity, and obesity-related health within their social and cultural context.
METHODS: Purposeful sampling was used to recruit daughters with a normal body
mass index (BMI) who have obese mothers. Individual semi-structured in-depth
interviews were conducted with 17 daughters (age 24 years) and 15 of their
mothers in Soweto, South Africa. Interview questions related to: a) eating and
physical activity behaviors and perceptions, b) perceptions of social and
community level factors, c) cultural beliefs about diet and body image, and d)
intergenerational relationships. Data were analyzed using four-phases of thematic
analysis and the constant comparison approach. RESULTS: Daughters and mothers had
similar ideas of the definition of healthy food and the importance of eating
healthy, but mothers were more likely to report eating healthy because of their
age, adverse health experiences, and a desire to live longer. Daughters and
mothers engaged in physical activity for reasons related to weight maintenance
and feeling better, but mothers reported being more likely to start exercising as
a result of a health concern. Daughters and mothers had comparable views of what
makes a person healthy. Daughters and mothers relied on each other for food
purchasing and food preparation. CONCLUSION: Daughters and mothers shared some
similar perceptions of diet, physical activity, and health that were rooted in
their daily life in Soweto. However, mothers generally reported being more likely
to exhibit healthy eating and physical activity behaviors despite being obese.
The mothers may have adopted these perceptions and behaviors later in life linked
to ageing and ill-health. It is possible that through exposure, their daughters
have assimilated these perceptions earlier in childhood or adolescence. It is
important to focus health promotion efforts around preventing the otherwise
expected increase of obesity among the young adult generation.
PMID- 27506679
TI - Clinical efficacy and safety of multidrug therapy including thrice weekly
intravenous amikacin administration for Mycobacterium abscessus pulmonary disease
in outpatient settings: a case series.
AB - BACKGROUND: Mycobacterium abscessus (M. abscessus) pulmonary disease is a
refractory chronic infectious disease. Options for treating M. abscessus
pulmonary disease are limited, especially in outpatient settings. Among
parenteral antibiotics against M. abscessus, intravenous amikacin (AMK) is
expected to be an effective outpatient antimicrobial therapy. This study
evaluated the clinical efficacy and safety of intravenous AMK therapy in
outpatients with M. abscessus pulmonary disease. METHODS: This retrospective
chart review of cases of M. abscessus pulmonary disease evaluated patient
background data, AMK dosage and duration, sputum conversion, clinical symptoms
radiological findings, and adverse events. M. massiliense was excluded on the
basis of multiplex PCR assay. RESULTS: Thirteen patients (2 men and 11 women)
with M. abscessus pulmonary disease were enrolled at 2 hospitals. The median age
at the initiation of intravenous AMK treatment was 65 years (range: 50-86 years).
Patients received a median AMK dose of 12.5 mg/kg (range: 8.3-16.2 mg/kg) for a
median duration of 4 months (range: 3-9 months). The addition of intravenous AMK
led to sputum conversion in 10 of 13 patients, and 8 patients continued to have
negative sputum status 1 year after treatment. Approximately half of the patients
showed improvement on chest high-resolution computed tomography. There were no
severe adverse events such as ototoxicity, vestibular toxicity, and renal
toxicity. CONCLUSIONS: Thrice weekly intravenous AMK administration in outpatient
settings is effective and safe for patients with M. abscessus pulmonary disease.
PMID- 27506680
TI - High T2-weighted signal intensity is associated with elevated troponin T in
hypertrophic cardiomyopathy.
AB - OBJECTIVE: Areas of high signal intensity (HighT2) on T2-weighted cardiovascular
magnetic resonance (CMR) imaging have been demonstrated in hypertrophic
cardiomyopathy (HCM). It has been hypothesised that HighT2 may indicate active
tissue injury in HCM. In this context, we studied HighT2 in relation to cardiac
troponin. METHODS: Outpatient HCM patients without a history of coronary artery
disease underwent CMR imaging at 1.5 T using T2-weighted, cine and late
gadolinium enhancement (LGE) imaging to assess HighT2, left ventricular (LV)
function, LV mass and the presence and extent of LGE. Highly sensitive cardiac
troponin T (hs-cTnT) was assessed as a marker of injury, with hs-cTnT >=14 and >3
ng/L defined as an elevated and detectable troponin. RESULTS: HighT2 was present
in 28% of patients (28/101). An elevated hs-cTnT was present in 54% of patients
with HighT2 (15/28) compared with 14% of patients without HighT2 (10/73)
(p<0.001). Hs-cTnT was detectable in 96% of patients with HighT2 (27/28) compared
with 66% of patients without HighT2 (48/73) (p=0.002). In case of an undetectable
hs-cTnT, HighT2 was only seen in 4% (1/26). In addition, the extent of HighT2 was
related with increasing hs-cTnT concentrations (Spearman's rho: 0.42, p<0.001).
CONCLUSIONS: In this CMR study of patients with HCM, we observed HighT2 in a
quarter of patients, and demonstrated that HighT2 was associated with an elevated
hs-cTnT. This observation, combined with the very high negative predictive value
of an undetectable hs-cTnT for HighT2, provides supportive evidence for the
hypothesis that HighT2 is indicative of recently sustained myocyte injury.
PMID- 27506681
TI - Transmission of HCV NS5A Inhibitor-Resistant Variants Among HIV-Infected Men Who
Have Sex With Men.
PMID- 27506683
TI - Reply to Skowronski et al.
PMID- 27506684
TI - Editorial Commentary: End-Stage Liver Disease in HIV Infection: An Avoidable
Burden?
PMID- 27506685
TI - Coexistence of MCR-1 and NDM-1 in Clinical Escherichia coli Isolates.
PMID- 27506686
TI - Repeat Influenza Vaccination and High-Dose Efficacy.
PMID- 27506687
TI - Treatment of Hospital or Ventilator-Associated Pneumonia Due to Carbapenem
Resistant Enterobacteriaceae: Leveraging Molecular Resistance Testing and
Combination Therapy to Improve Outcomes.
PMID- 27506682
TI - Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in
North America From the Early to Modern Antiretroviral Therapy Eras.
AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients coinfected with
hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver
disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is
unknown. METHODS: Twelve clinical cohorts in the United States and Canada
participating in the North American AIDS Cohort Collaboration on Research and
Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate
ratios according to hepatitis status adjusted for age, sex, race, cohort, time
updated CD4 cell count and HIV RNA were estimated in calendar periods
corresponding to major changes in antiretroviral therapy: early (1996-2000),
middle (2001-2005), and modern (2006-2010) eras. RESULTS: Among 34 119 HIV
infected adults followed for 129 818 person-years, 380 incident ESLD outcomes
occurred. ESLD incidence (per 1000 person-years) was highest in triply infected
(11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV
monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals)
comparing the modern to the early antiretroviral era were 0.95 (.61-1.47) for
HCV, 0.95 (.40-2.26) for HBV, and 1.52 (.46-5.02) for triply infected patients.
Use of antiretrovirals dually activity against HBV increased over time. However,
in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir.
There was little use of HCV therapy. CONCLUSIONS: Despite increasing use of
antiretrovirals, no clear reduction in ESLD risk was observed over 15 years.
Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based
regimens for HBV should be prioritized for coinfected patients.
PMID- 27506688
TI - The Burden of Hepatitis C Infection-Related Liver Fibrosis in the United States.
AB - BACKGROUND: Knowledge of the estimated proportion of hepatitis C virus (HCV)
infected persons with advanced fibrosis or cirrhosis is critical to estimating
healthcare needs. METHODS: We analyzed HCV-related testing conducted by Quest
Diagnostics from January 2010 through December 2013. Tests included hepatitis C
antibody, HCV RNA, HCV genotype (nucleic acid tests [NAT]), liver function tests,
and platelet counts; patient age was also determined. Aspartate aminotransferase
(AST)-to-platelet ratio (APRI) was calculated as = 100*(aspartate
aminotransferase [AST]/upper limit of AST)/platelet. Fibrosis-4 (FIB-4) was
calculated as (age * AST)/(platelet *? alanine aminotransferase [ALT]). Persons
were "currently infected" if they had >=1 positive HCV NAT; "in care" if a
positive RNA test was followed <6 months by >=1 additional NAT(s), or ALT, AST,
and platelets <90 days, or any test ordered by an infectious diseases or
gastroenterology specialist; and "evaluated for treatment" if they had a genotype
test. RESULTS: Approximately 10 million HCV test results were analyzed,
representing 5.6 million unique patients. Of the 2.6 million patients with data
to estimate liver disease, 5% were currently infected. Among those currently
infected, APRI and FIB-4 scores indicated that 23% overall-and 27% among the
cohort born during 1945-1965-had advanced fibrosis or cirrhosis at first
diagnosis. A total of 54% of infected were in care and 51% of infected with
advanced fibrosis or cirrhosis were evaluated for treatment. CONCLUSIONS: Testing
from a large US commercial laboratory indicates that about 1 in 4 HCV-infected
persons have levels of liver disease put them at highest risk for complications
and could benefit from immediate antiviral therapy.
PMID- 27506690
TI - Elections, scare campaigns and Medicare: Towards a balanced scorecard.
PMID- 27506689
TI - Effect of a Dengue Clinical Case Management Course on Physician Practices in
Puerto Rico.
AB - BACKGROUND: Prior to 2010, the clinical management of dengue in Puerto Rico was
inconsistent with World Health Organization guidelines. A 4-hour classroom-style
course on dengue clinical management was developed in 2009 and mandated for
Puerto Rico medical licensure in 2010. Fifty physicians were trained as "master
trainers" and gave this course to 7638 physicians. This study evaluated the
effect of the course on the clinical management of hospitalized dengue patients.
METHODS: Pre- and post-course test responses were compared. Changes in physician
practices were assessed by reviewing medical records of 430 adult and 1075
pediatric dengue patients at the 12 hospitals in Puerto Rico that reported the
most cases during 2008-2009 (pre-intervention) and 2011 (post-intervention).
Mixed-effects logistic regression was used to compare key indicators of dengue
management. RESULTS: Physician test scores increased from 48% to 72% correct.
Chart reviews showed that the percentage of adult patients who did not receive
corticosteroids increased from 30% to 68% (odds ratio [OR], 5.9; 95% confidence
interval [CI], 3.7-9.5) and from 91% to 96% in pediatric patients (OR, 2.7; 95%
CI, 1.5-4.9). Usage of isotonic intravenous saline during the critical period
increased from 57% to 90% in adult patients (OR, 6.2; 95% CI, 1.9-20.4) and from
25% to 44% in pediatric patients (OR, 3.4; 95% CI, 2.2-5.3). CONCLUSIONS:
Management of dengue inpatients significantly improved following implementation
of a classroom-style course taught by master trainers. An online version of the
course was launched in 2014 to expand its reach and sustainability.
PMID- 27506691
TI - Prognostic Features for Objectively Defined Urinary Continence after Radical
Cystectomy and Ileal Orthotopic Neobladder in a Contemporary Cohort.
AB - PURPOSE: We objectively quantified daytime and nocturnal continence rates, and
defined predictive features for favorable continence outcomes after radical
cystectomy and orthotopic ileal neobladder creation. MATERIALS AND METHODS: At 1
institution 1,012 cystectomies were performed between 2004 and 2015.
Questionnaires evaluating the continence status were sent to 244 patients. To
objectify postoperative urine loss daytime and nocturnal pad tests were
performed. Continence was defined as the need for up to 1 safety pad and urine
loss 10 gm or less per test. Predefined associative features were tested for an
influence on continence outcomes. Statistical analysis was done with the Fisher
exact and Mann-Whitney U tests, and linear logistic regression models.
Significance was considered at p <0.05. RESULTS: A total of 188 patients (77.0%)
returned the questionnaires. Median followup was 61 months. Median daytime pad
use was 1 pad per day (range 0 to 9). Median daily urine loss based on
standardized pad testing was 8 gm (range 0 to 2,400). During the night a median
of 1 pad (range 0 to 7) was used and median nocturnal urine loss was 28.5 gm
(range 0 to 1,220). The continence rate was 54.3% during the day and 36.3% at
night. On multivariate analysis good preoperative ECOG (Eastern Cooperative
Oncology Group) status (OR 2.987, p = 0.010), retained sensation of bladder
filling (OR 6.462, p = 0.003) and preoperative coronary heart disease (OR 0.036,
p = 0.002) were independent predictors of daytime success. Based on preoperative
risk factors a simple predictive score for daytime continence was created (AUC
0.725, p <0.001). CONCLUSIONS: Continence rates after orthotopic ileal neobladder
creation are lower than previously described when objective continence
definitions are applied. Patients with good performance status, without coronary
heart disease and with retained sensation of orthotopic ileal neobladder filling
have better daytime continence outcomes.
PMID- 27506692
TI - Epidemiology of Genitourinary Injuries among Male U.S. Service Members Deployed
to Iraq and Afghanistan: Early Findings from the Trauma Outcomes and Urogenital
Health (TOUGH) Project.
AB - PURPOSE: In this study we report the number, nature and severity of genitourinary
injuries among male U.S. service members deployed to Operations Iraqi Freedom and
Enduring Freedom. MATERIALS AND METHODS: This retrospective cross-sectional study
of the Department of Defense Trauma Registry used ICD-9-CM codes to identify
service members with genitourinary injuries, and used Abbreviated Injury Scale
codes to determine injury severity, genitourinary organs injured and comorbid
injuries. RESULTS: From October 2001 to August 2013, 1,367 male U.S. service
members sustained 1 or more genitourinary injuries. The majority of injuries
involved the external genitalia (1,000, 73.2%), including the scrotum (760,
55.6%), testes (451, 33.0%), penis (423, 31%) and/or urethra (125, 9.1%). Overall
more than a third of service members with genitourinary injury sustained at least
1 severe genitourinary injury (502, 36.7%). Loss of 1 or both testes was
documented in 146 men, including 129 (9.4%) unilateral orchiectomies and 17
(1.2%) bilateral orchiectomies. Common comorbid injuries included traumatic brain
injury (549, 40.2%), pelvic fracture (341, 25.0%), colorectal injury (297, 21.7%)
and lower extremity amputations (387, 28.7%). CONCLUSIONS: An unprecedented
number of U.S. service members sustained genitourinary injury while deployed to
Operation Iraqi Freedom/Operation Enduring Freedom. Further study is needed to
describe the long-term impact of genitourinary injury and determine the potential
need for novel treatments to improve sexual, urinary and/or reproductive function
among service members with severe genital injury.
PMID- 27506693
TI - The Impact of Repeat Prostate Biopsies on Oncologic, Pathological and
Perioperative Outcomes after Radical Prostatectomy.
AB - PURPOSE: The impact of repeat biopsy sessions on radical prostatectomy remains
controversial regarding perioperative, pathological and oncologic outcome.
MATERIALS AND METHODS: We analyzed the records of 12,624 patients who underwent
radical prostatectomy from 2007 to 2013. The association of the number of biopsy
sessions (range 1 to 3 or more) with pathological outcomes and perioperative
complications was analyzed using the Wilcoxon matched pair test. To test the
association between biopsy sessions and biochemical recurrence-free survival we
used Kaplan-Meier curves and multivariable Cox regression analysis. RESULTS: Of
the patients 89.2% had 1 biopsy session, 7.4% had 2 sessions and 3.4% had 3 or
more sessions. Median followup was 36.6 months. In patients with 1, 2 and 3 or
more biopsy sessions prostate volume (38, 44 and 45 ml) and prostate specific
antigen (6.7, 7.6 and 10.1 ng/ml, respectively) were greater (each p <0.001). The
perioperative outcome was more favorable. Patients with 1, 2 and 3 or more biopsy
sessions more often had organ confined tumors (67.6%, 72.1% and 72.9%, p = 0.003)
and higher tumor volume (3.1, 3.0 and 3.6 ml, p <0.001) but a lower tumor percent
(7.5%, 3.7% and 2.4%, respectively, p <0.001). More biopsy sessions were
associated with fewer lymph node metastases (1, 2 and 3 sessions 0.23, 0.13 and
0.17, respectively, p <0.001). Gleason score and surgical margin status did not
differ. The overall biochemical recurrence rate was 18.9% and it was comparable
among the biopsy groups. No association was found between the number of biopsies
and biochemical recurrence. CONCLUSIONS: Patients with multiple biopsy sessions
experience a slightly more favorable pathological outcome without an impact on
the oncologic outcome. The perioperative outcome was more favorable in patients
with multiple biopsies.
PMID- 27506694
TI - Emotional Distress Increases the Likelihood of Undergoing Surgery among Men with
Localized Prostate Cancer.
AB - PURPOSE: We determined whether among men with clinically localized prostate
cancer, particularly men with low risk disease, greater emotional distress
increases the likelihood of undergoing surgery vs radiation or active
surveillance. MATERIALS AND METHODS: Participants were 1,531 patients recruited
from 2 academic and 3 community facilities (nonHispanic white 83%, nonHispanic
black 11% and Hispanic 6%; low risk 36%, intermediate risk 49% and high risk 15%;
choice of active surveillance 24%, radiation 27% and surgery 48%). Emotional
distress was assessed shortly after diagnosis and after men made a treatment
decision with the Distress Thermometer. We used multinomial logistic regression
with robust standard errors to test if emotional distress at either point
predicted treatment choice in the sample as a whole and after stratifying by
D'Amico risk score. RESULTS: In the sample as a whole the participants who were
more emotionally distressed at diagnosis were more likely to choose surgery over
active surveillance (RRR 1.07; 95% CI 1.01, 1.14; p=0.02). Men who were more
distressed close to the time they made a treatment choice were more likely to
have chosen surgery over active surveillance (RRR 1.16; 95% CI 1.09, 1.24; p
<0.001) or surgery over radiation (RRR 1.12; 95% CI 1.05, 1.19; p=0.001). This
pattern was also found in men with low risk disease. CONCLUSIONS: Emotional
distress may motivate men with low risk prostate cancer to choose more aggressive
treatment. Addressing emotional distress before and during treatment decision
making may reduce a barrier to the uptake of active surveillance.
PMID- 27506695
TI - Linkage of Lower Urinary Tract Symptoms to Sleep Quality in Elderly Men with
Nocturia: A Community Based Study Using Home Measured Electroencephalogram Data.
AB - PURPOSE: We objectively investigated the relationship between sleep
quality/efficiency and factors associated with micturition using at-home
electroencephalogram assessment. MATERIALS AND METHODS: Participants were
recruited from among those enrolled in the Fujiwara-kyo Study, a community based
longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included
participants were men at least 65 years old who woke up in the middle of the
night/early morning at least 3 times per week with the urge to void. We evaluated
lower urinary tract symptoms using the I-PSS and subjective sleep quality using
the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume
charting measurements were also obtained. Electroencephalogram recordings were
obtained during sleep to evaluate objective sleep quality. RESULTS: Final
analysis included data from 47 participants. I-PSS-quality of life score and slow
wave sleep time were independent predictors of good subjective sleep quality as
determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was
an independent predictor of greater sleep efficiency. Maximum flow rate was an
independent predictor of longer slow wave sleep time. CONCLUSIONS: In elderly men
with nocturia, sleep quality is associated with lower urinary tract function.
Higher subjective sleep quality is associated with longer slow wave sleep time
and less severe lower urinary tract symptoms. Higher objective sleep quality is
further associated with a higher urinary flow rate and lower nocturnal urinary
volume.
PMID- 27506696
TI - Suppressed Recurrent Bladder Cancer after Androgen Suppression with Androgen
Deprivation Therapy or 5alpha-Reductase Inhibitor.
AB - PURPOSE: We determined whether intravesical recurrence is affected by inhibition
of androgen signaling among men with nonmuscle invasive bladder cancer. MATERIALS
AND METHODS: We examined the intravesical recurrence rate among men treated with
or without androgen suppression therapy by androgen deprivation therapy for
prostate cancer or 5alpha-reductase inhibitor dutasteride for benign prostatic
hyperplasia. RESULTS: We studied 228 men, including 32 with and 196 without
androgen suppression therapy. During a median followup of 3.6 and 3.0 years
intravesical recurrence developed in 4 (12.5%) and 59 men (30.1%) with and
without androgen suppression therapy, respectively. On multivariate analysis
multiple tumors (HR 1.82, p = 0.027), a large tumor (HR 2.13, p = 0.043) and ever
smoking (HR 2.45, p = 0.020) as well as the presence of androgen suppression
therapy (HR 0.36, p = 0.024) were independent risk factors for intravesical
recurrence. Notably, tumor progressed to muscle invasive bladder cancer in 6 men
(3.1%) without androgen suppression therapy. No man with androgen suppression
therapy progressed to muscle invasive bladder cancer. CONCLUSIONS: Our study
suggests the possibility of androgen suppression therapy as prophylaxis for
intravesical recurrence of bladder cancer. Further explorations are warranted of
the prophylactic effect of androgen suppression therapy on bladder cancer
pathogenesis.
PMID- 27506697
TI - Circadian Rhythms in Water and Solute Handling in Adults with a Spinal Cord
Injury.
AB - PURPOSE: We evaluated nocturnal urine production and circadian rhythms of renal
function (glomerular filtration, and water and solute diuresis) in adults with
spinal cord injury compared to controls. MATERIALS AND METHODS: This prospective
observational study was done at Ghent University Hospital, Belgium. Participants
were asked to perform a 24-hour urine collection. A blood sample was taken to
calculate the diuresis rate and the renal clearance of creatinine, free water,
solutes, sodium and urea. RESULTS: A total of 119 patients were divided into 32
with spinal cord injury, and 68 controls with and 19 without nocturnal polyuria.
Spinal cord injured patients showed no circadian rhythms in the diuresis rate or
in the renal clearance of creatinine, free water, solutes, sodium or urea.
Controls without nocturnal polyuria reported a lower nighttime diuresis rate and
lower nighttime clearance of creatinine, solutes, sodium and urea compared to
daytime levels. Controls with nocturnal polyuria had no circadian rhythms in the
diuresis rate or creatinine clearance and a significant increase in nocturnal
free water clearance compared to daytime levels. CONCLUSIONS: Comparing the
mechanisms underlying nocturnal urine production between patients with spinal
cord injury and controls revealed important differences. Spinal cord injured
patients showed absent circadian rhythms in the renal clearance of creatinine
(glomerular filtration), free water (water diuresis) and solutes such as sodium
and urea (solute diuresis). Future research must be done to evaluate the role of
patient stratification to find the most effective and safe treatment or
combination of treatments for spinal cord injured patients with complaints or
complications related to nocturnal polyuria.
PMID- 27506698
TI - Priority of Treatment Outcomes for Caregivers and Patients with Mild Cognitive
Impairment: Preliminary Analyses.
AB - INTRODUCTION: The patient-centered movement advocates for greater attention to
the outcomes that matter most to patients and their families. In
neurodegenerative disease, determination of patient and caregiver priorities has
received scant attention in part because dementia patients are deemed unreliable
reporters. However, people with mild cognitive impairment (MCI) likely retain
capacity to report their preferences. METHODS: In two separate MCI cohorts, we
conducted preliminary analyses of patient and caregiver priorities among seven
patient and five caregiver outcomes of the HABIT(r) Healthy Action to Benefit
Independence & Thinking program (Mayo Clinic, Rochester, MN, USA). RESULTS: Via
interview and paper-and-pencil reporting both patient and caregiver respondents'
ranked patient and caregiver quality of life and patient self-efficacy as highest
priorities, ranking them ahead of patient and caregiver mood, patient functional
status, patient distressing behaviors and caregiver burden. Patients and
caregivers tended to value the outcomes for their loved ones higher than their
own outcomes. CONCLUSION: Caregivers appeared to be reasonable, but not perfect,
proxies for patient reports. Additional research with larger cohorts and a more
comprehensive range of outcomes is needed.
PMID- 27506699
TI - What is this image? 2016: Image 3.
PMID- 27506701
TI - Cardiac sarcoidosis: An important niche for PET, but a journey just begun.
PMID- 27506700
TI - The radiation dose to overweighted patients undergoing myocardial perfusion SPECT
can be significantly reduced: validation of a linear weight-adjusted activity
administration protocol.
AB - BACKGROUND: Large body size can cause a higher proportion of emitted photons
being attenuated within the patient. Therefore, clinical myocardial perfusion
SPECT (MPS) protocols often include unproportionally higher radioisotope activity
to obese patients. The aim was to evaluate if a linear weight-adjusted low-dose
protocol can be applied to obese patients and thereby decrease radiation
exposure. METHODS AND RESULT: Two hundred patients (>110 kg, BMI 18-41, [n = 69],
<= 110 kg, BMI 31-58, [n = 131]) underwent 99mTc-tetrofosmin stress examination
on a Cadmium Zinc Telluride or a conventional gamma camera using new generations
of reconstruction algorithm (Resolution Recovery). Patients <110 kg were
administered 2.5 MBq/kg, patients between 110 and 120 kg received 430 MBq and
patients >120 kg received 570 MBq according to clinical routine. Patients >110 kg
had 130% total number of counts in the images compared to patients <110 kg.
Recalculating the counts to correspond to an administered activity of 2.5 MBq/kg
resulted in similar number of counts across the groups. Image analyses in a
subgroup with images corresponding to high activity and 2.5 MBq/kg showed no
difference in image quality or ischemia quantification. CONCLUSION: Linear low
dose weight-adjusted protocol of 2.5 MBq/kg in MPS can be applied over a large
weight span without loss of counts or image quality, resulting in a significant
reduction in radiation exposure to obese patients.
PMID- 27506702
TI - Prognostic value of one millisievert exercise myocardial perfusion imaging in
patients without known coronary artery disease.
AB - : The aim of this study was to assess the prognostic value of normal ultra-low
dose exercise MPI with a CZT camera. METHODS: 1901 consecutive patients without
known CAD referred for exercise MPI with 1.8 MBq/kg (0.05 mCi) of Tc99m sestamibi
or tetrofosmin and a CZT camera were included prospectively. Patients with an
abnormal scan requiring an additional resting image (230) or a submaximal
exercise test (271) were excluded. The 1400 remaining patients were followed for
39 months. The primary end-point was cardiac events (cardiac death, nonfatal
myocardial infarction, and revascularization). The secondary end-point was
noncardiac death. RESULTS: The mean injected activity was 145 +/- 37 MBq (3.9 +/-
1 mCi), the mean acquisition duration was 10 +/- 0.7 minutes, and the mean
effective dose was 0.91 +/- 0.13 mSv. 1288 patients (92%) achieved full follow
up. We observed 22 cardiac events and 16 noncardiac deaths. The annualized rates
were equivalent to 0.55% for cardiac events and 0.37% for noncardiac mortality.
CONCLUSIONS: Normal ultra-low-dose exercise MPI with a CZT camera has a high
negative predictive value. The effective dose was less than 1 mSv, and the study
thus allays concerns about radiation burden.
PMID- 27506703
TI - [18F]-Sodium fluoride uptake in Takayasu arteritis.
AB - BACKGROUND: While 18F-fluorodeoxyglucose and 18F-sodium fluoride with positron
emission tomography relate with inflammation and calcification, their role in the
assessment of patients with Takayasu arteritis has not yet been studied. METHODS:
We present 5 patients with suspected active metabolic disease who underwent PET
with 18F-fluorodeoxyglucose and 18F-sodium fluoride in order to explore the
locations and correlations of 18F-fluorodeoxyglucose and 18F-sodium fluoride
uptakes. Diagnosis of metabolic active disease was based on 18F
fluorodeoxyglucose uptake. RESULTS: We studied 3 female patients and 2 male
patients. Median age was 29 years (min: 19 max: 63). In areas with
atherosclerotic plaques, we found a negative correlation between 18F-sodium
fluoride and 18F-fluorodeoxyglucose uptakes (r = -0.78) (P = .001). Meanwhile, in
areas with only metabolic active disease, we found a positive correlation between
18F-sodium fluoride and 18F-fluorodeoxyglucose uptakes (r = 0.94) (P = .019).
CONCLUSIONS: In Takayasu arteritis, 18F-sodium fluoride uptake can document
different stages of metabolic disease, even in the absence of active metabolic
disease or symptoms.
PMID- 27506704
TI - The Utility of Cannabidiol in the Treatment of Refractory Epilepsy.
AB - Cannabis-derived cannabinoids such as cannabidiol (CBD) have anticonvulsant
properties. Recently, there has been an emerging interest in the use of CBD
enriched products for treatment of drug-resistant epilepsy. Some pilot trials of
CBD have proved beneficial for refractory epilepsy, but its efficacy is yet to be
confirmed by standard placebo-controlled trials. However, the mechanisms
underlying the seizure protection efficacy claims of CBD remain unclear. This
review briefly describes the clinical utility of CBD in the treatment of
refractory epilepsy.
PMID- 27506705
TI - 3,3',5,5'-Tetramethylbenzidine Oxidation on Paper Devices for Horseradish
Peroxidase-based Assays.
AB - We report on the colorimetric oxidation of 3,3',5,5'-tetramethylbenzidine (TMB)
by hydrogen peroxide using horseradish peroxidase on photolithography-fabricated
(P-PAD) and wax-printed (W-PAD) paper-based analytical devices. Fabricating PADs
via photolithography exposes the hydrophilic areas to polymers (photoresists) and
solvents, not only reducing the hydrophilicity, but also affecting the TMB-H2O2
assay system with an unavoidable incomplete elimination of photoresist during
fabrication. Detection signals are then observed in the presence of photoresist
residues on the P-PAD, even at a blank HRP concentration.
PMID- 27506706
TI - A Simple and Sensitive Method for Auramine O Detection Based on the Binding
Interaction with Bovin Serum Albumin.
AB - A simple, rapid and effective method for auramine O (AO) detection was proposed
by fluorescence and UV-Vis absorption spectroscopy. In the BR buffer system (pH
7.0), AO had a strong quenching ability to the fluorescence of bovin serum
albumin (BSA) by dynamic quenching. In terms of the thermodynamic parameters
calculated as DeltaH > 0 and DeltaS > 0, the resulting binding of BSA and AO was
mainly attributed to the hydrophobic interaction forces. The linearity of this
method was in the concentration range from 0.16 to 50 MUmol L(-1) with a
detection limit of 0.05 MUmol L(-1). Based on fluorescence resonance energy
transfer (FRET), the distance r (1.36 nm) between donor (BSA) and acceptor (AO)
was obtained. Furthermore, the effects of foreign substances and ionic strength
were evaluated under the optimum reaction conditions. BSA as a selective probe
could be applied to the analysis of AO in medicines with satisfactory results.
PMID- 27506707
TI - New Electrochemical Evaluation of the Antioxidant Capacity of Beverages with
Polyoxometalates as Redox Probes.
AB - A new method was developed to evaluate antioxidant activity based on the redox
properties of polyoxometalates, which are partially reduced by antioxidants to
generate a limiting potential. The polyoxometalates [PMo12O40](3-), [PVW11O40](4
) and [SV2W10O40]4- formed in situ were used as electrochemical probes for the
new evaluation method, and their formation conditions were optimized to evaluate
the antioxidant activities of gallic acid, ellagic acid, catechin, quercetin,
morin, trans-ferulic acid, sesamol, alpha-tocopherol, delta-tocopherol and L
ascorbic acid. The observed difference between initial potential and limiting
potential (DeltaE) were compared with spectrophotometrically evaluated
antioxidant activities. In addition, the antioxidant capacities of five beverages
(Japanese green tea, concentrated catechin-containing green tea, grapefruit
juice, red wine and Japanese sake) were evaluated.
PMID- 27506708
TI - Differentiation of the Isomers of N-Alkylated Cathinones by GC-EI-MS-MS and LC
PDA.
AB - Synthetic compounds structurally derived from the mild stimulant 2-amino-1-phenyl
1-propanone, known as cathinone derivatives, are one of the largest growing class
of synthetic designer drugs. The characterization of these drugs is complicated
by the structural diversity and similarity of compounds in the ever-growing
cathinone family. This paper demonstrates the successful application of gas
chromatography-electron ionization-tandem mass spectrometry (GC-EI-MS-MS) and
liquid chromatography-photodiode array (LC-PDA) analysis to differentiate
structurally similar derivatives including regioisomers of cathinones. Product
ion spectrometry of iminium ions allows for an univocal differentiation of the
studied cathinones with the same aminoalkyl moiety. Furthermore, the product ion
spectrometry of acylium ions and ultraviolet spectra obtained by LC-PDA enabled
differentiation of regioisomers resulting from different substitution patterns on
the aromatic ring. The validity of the method was demonstrated by the analysis of
N-alkylated ortho-, meta-, and para-alkylcathinones along with the scaffolds of
buphedrones and pentiophenones.
PMID- 27506709
TI - Determination of Iodide, Iodate and Total Iodine in Natural Water Samples by HPLC
with Amperometric and Spectrophotometric Detection, and Off-line UV Irradiation.
AB - We developed a rapid, simple method for the iodine speciation analysis of water
and applied it to natural water samples. Simultaneous determinations of I(-) and
IO3(-) were achieved with an HPLC system with amperometric detection for I(-) and
spectrophotometric detection after a postcolumn reaction for IO3(-). We
determined the I(-) and IO3(-) concentrations in 20-MUL water samples within 10
min. Total I concentrations in water samples were determined after the
decomposition of organics by off-line UV irradiation for 30 min, followed by
reduction to I(-). The analytical conditions were optimized by using test
solutions rich in organic matter extracted from soils. We tested the new method
with samples of groundwater, spring water, precipitation, soil percolate, stream
water, and seawater as well as solutions extracted from soil. The method worked
well, although the concentrations of some I species were below detection. This
method is suitable for routine speciation analysis, which is important for
studies of I behavior in the environment.
PMID- 27506710
TI - Development of Sensitive Analytical Approach for the Quantification of alpha
Lipoic Acid Using Boron Doped Diamond Electrode.
AB - A boron doped diamond (BDD) electrode was investigated for use as an
electrochemical sensor for alpha-lipoic acid (LA) using amperometric and
differential pulse voltammetric detection. LA displays a well expressed oxidation
peak at +0.9 V vs. Ag/AgCl in solutions with a pH value of 3. It was found that
signals obtained are linearly related to the concentration range from 0.3 to 105
MUM with detection limit of 0.088 MUM. Interferences by common compounds such as
ascorbic acid, uric acid and dopamine were tested and the method was successfully
applied to the determination of LA in human body fluids where it gave recoveries
in the range from 95 to 97%.
PMID- 27506711
TI - Electrochemical Sensing of Casein Based on the Interaction between Its Phosphate
Groups and a Ruthenium(III) Complex.
AB - A reaction to casein, along with beta-lactoglobulin, is a main cause of milk
allergies, and also is a useful indicator of protein in allergic analyses. In the
present study, a simple casein sensor was developed based on the interaction
between a phosphate group of casein and electroactive [Ru(NH3)6](3+). We
evaluated the voltammetric behavior of a casein-[Ru(NH3)6](3+) complex using a
glassy carbon electrode. When the ruthenium(III) complex was combined with the
phosphate groups of casein, the structure of the casein was changed. Since the
hydrophobicity of casein was increased due to the binding, the casein was
adsorbed onto the electrode. Furthermore, we modified an electrode with a
ruthenium(III) ions/collagen film. When the sensor was applied to the detection
of the casein contained in milk, the values coincided with those indicated by the
manufacturer. Accordingly, this electrode could be a powerful sensor for the
determination of casein in several foods.
PMID- 27506712
TI - Raman Spectral Analysis of Low-content Benzene Concentration in Gasoline with
Partial Least Squares Based on Interference Peak Subtraction.
AB - Raman spectroscopy is adopted to detect the low-content benzene concentrations in
gasoline products. Due to the peak overlap of benzene and other species in the
gasoline spectrum, the associated statistical regression methods cannot make
stable predictions unless there are enough training samples. To extend their
extrapolation to small-size training sets, we propose the method of partial least
squares based on a spectral pretreatment of interference peak subtraction (IPS
PLS). During the analysis, after spectral interpolation and baseline removal, we
extract the benzene peak by interference peak subtraction (IPS), and then partial
least squares (PLS) is applied to make a prediction. The experimental results
demonstrate that, IPS can extract benzene information effectively, and help to
decrease principal components needed by PLS, thus IPS-PLS is superior to direct
PLS with small-size training sets, and depends less on the training sample
distribution. Meanwhile, IPS-PLS can reach the standard of ASTM 3606-10 with the
least of 9 training samples, while keeping its max predictive error less than
0.1254% (v/v), which shows promising prospects in gasoline quality test.
PMID- 27506713
TI - Use of Ni/NixB Nanoparticles as a Novel Adsorbent for the Preconcentration of
Mercury Species prior to Cold Vapor-Atomic Fluorescence Spectrometric
Determination.
AB - A selective matrix separation/enrichment method, utilizing a simple batch
procedure with nickel/nickel boride (Ni/NixB) nanoparticles was proposed for the
determination of inorganic mercury(II), Hg(2+) and methyl mercury(I), CH3Hg(+) in
waters prior to cold vapor-atomic fluorescence spectrometry (CV-AFS). The Ni/NixB
nanoparticles, were synthesized by the chemical reduction of Ni(II) to Ni/NixB.
The novel adsorbent was selective to Hg(2+) and CH3Hg(+) species between pH
values of 4 - 10. Both of the mercury species were recovered from the adsorbent
using 1.0 mol L(-1) hot HNO3 with high efficiency. It was observed that the
adsorbent selectively removed Hg(2+) and CH3Hg(+) from the bulk solution in the
presence of several competitor ions (As(3+), Sb(3+), Pb(2+), Zn(2+), Cu(2+),
Cd(2+) and Fe(3+)) with >=96% adsorption. The limit of detection (3sigma above
blank) was found to be 1.8 ng L(-1) with a preconcentration factor of 20. The
validation of the method was tested through spike recovery experiments with
several water samples (tap and seawater) at MUg L(-1) concentration levels, and
all recovery values were found to vary between 95 and 105%.
PMID- 27506714
TI - Stepwise Preparation of Spherical Gold Nanoparticles Passivated with Cationic
Amphiphiles.
AB - Spherical gold nanoparticles with cationic surfaces were prepared in
hexadecyltrimethylammonium (CTA(+)) chloride (CTAC) and CTA(+) bromide (CTAB)
solutions. In a CTAC solution, ascorbic acid reduction of gold ions (AuCl4(-))
induced spontaneous nucleation of gold clusters, which resulted in the formation
of small gold nanoparticles (<5 nm). In a CTAB solution, the combination of
ascorbic acid and AuBr4(-) induced low spontaneous nucleation, and therefore
controllable crystal growth of seed particles was possible. To obtain uniform
gold nanoparticles, seed particles (<5 nm) were first prepared in a CTAC solution
using NaBH4 as a reducing agent. Subsequent growth reactions of the seeds in CTAB
solutions were controllable to obtain gold nanoparticles with diameters ranging
from 7 to 60 nm.
PMID- 27506715
TI - Electrochemical Determination of Bisphenol A with Pencil Graphite Electrodes
Modified with Co(II), Ni(II), Cu(II) and Fe(II) Phthalocyaninetetrasulfonates.
AB - Pencil graphite electrodes modified with Co(II), Ni(II), Cu(II) and Fe(II)
metallophthalocyaninetetrasulfonates (MePcTSs) were investigated for an
electrochemical determination of bisphenol A (BPA). The electrochemical
performances of the modified electrodes for different pH values in phosphate and
the Britton-Robinson buffers were determined by cyclic voltammetry; the electrode
performances were better in the Britton-Robinson buffer. NiPcTS and CoPcTS
modifications of the electrodes had remarkable enhancements on their
performances. The differential pulse voltammetry parameters for the electrodes
were optimized, and we found that the electrochemical response versus the
concentration of BPA is linear from 5.0 * 10(-7) to 1.0 * 10(-5) M for the NiPcTS
and CoPcTS modified electrodes. The detection limits of these modified electrodes
are 2.9 * 10(-7) and 4.3 * 10(-7) M, respectively, and the effects of interfering
species are less than 5%. The results show that NiPcTS and CoPcTS modified pencil
graphite electrodes could be used for electrochemical determinations of BPA for
analytical purposes.
PMID- 27506716
TI - A Label-free, Highly Sensitive and Selective Detection of Hemin Based on the
Competition between Hemin and Protoporphyrin IX Binding to G-Quadruplexes.
AB - Herein is reported a simple and label-free fluorescent detection method for hemin
based on using protoporphyrin IX (PPIX) as a fluorescent signal reporter. PPIX
emits weak fluorescence in an aqueous solution. When PPIX binds to G
quadruplexes, the fluorescence intensity of PPIX is greatly increased. While in
the presence of target hemin, hemin competes with PPIX toward G-quadruplexes
because its affinity to G-quadruplexes is higher than that of PPIX. With the
formation of the hemin-G-quadruplex complex, PPIX is released to the solution
from the G-quadruplex accompanied by quenching of the fluorescence of the system.
This fluorescence change of the system can be used to monitor hemin with a low
detection limit of 36 nM. In addition, the possible binding sites for PPIX
binding to the G-quadruplex are discussed based on competition between hemin and
PPIX. What is more, this method might pave the way for applying G-quadruplexes
and PPIX to more sensing systems.
PMID- 27506717
TI - Amino Acid Metabolomics Using LC-MS/MS: Assessment of Cancer-Cell Resistance in a
Simulated Tumor Microenvironment.
AB - We performed a comprehensive quantification of 20 amino acids in RPMI 1640 medium
cultured human colorectal adenocarcinoma cells to evaluate the efficacy of 5
fluorouracil treatment under hypoxic and hypoglycemic conditions, which mimic the
tumor microenvironment. In this study, we developed a simple and comprehensive
analytical method by using LC-MS/MS connected to the Intrada amino acid column,
which eluted amino acids within 9 min. The present method covered a linearity
range of 3.6 - 1818 MUM, except for Gly (227 - 1818 MUM), Ala, Asp, His (7.1 -
1818 MUM each), and Trp (3.6 - 909 MUM). The limits of detection were in the
range of 0.02 - 38.0 pmol per injection in a standard solution. Amino acid
concentration data were analyzed using principal-component analysis to represent
samples on two-dimensional graphs. Linear discriminant analysis was used to
classify samples on the score plots. Using this approach, the effect of 5
fluorouracil treatment could be successfully discriminated at high discrimination
rates. Moreover, several amino acids were extracted from corresponding loading
plots as candidate markers for distinguishing the effects of the 5-fluorouracil
treatment or tumor microenvironmental conditions. These results suggest that our
proposed method might be a useful tool for evaluating the efficacy of anticancer
drugs in the tumor microenvironment.
PMID- 27506718
TI - Colorimetric Coupled Enzyme Assay for Cystathionine beta-Synthase.
AB - A colorimetric coupled enzyme assay for the determination of cystathionine beta
synthase activity is described. The method exploits cystathionine gamma-lyase as
an ancillary enzyme capable of transforming cystathionine, produced by
cystathionine beta-synthase, into cysteine. The cysteine is then
spectrophotometrically detected at 560 nm, after its specific complexation with
ninhydrin. This method was used to detect cystathionine beta-synthase in crude
extracts, and for the kinetic characterization of the enzyme partially purified
from bovine kidney. A rapid two-step protocol is described for the partial
purification of cystathionine gamma-lyase from bovine kidney, aimed at a suitable
and stable ancillary enzyme preparation.
PMID- 27506719
TI - Investigation of 5-(3-Trifluoromethylbenzylidene)thiazolidine-2,4-dione as a
Matrix for Analyses of Biogenic Monoamine Transmitters Using MALDI-MS.
AB - In order to discover new matrices suitable for the analyses of low molecular
weight compounds using positive-ion mode matrix-assisted laser
desorption/ionization (MALDI) time-of-flight mass spectrometry (MS), 5-(3
trifluoromethylbenzylidene)thiazolidine-2,4-dione (3-CF3-BTD) was synthesized,
and its effectiveness was compared with that when commercially available alpha
cyano-4-hydroxycinnamic acid was used. 3-CF3-BTD was sufficiently sensitive to
analyze neurotransmitters, i.e., dopamine, serotonin, histamine, and epinephrine,
in amounts of several picomoles. Similar to vacuum MALDI experiments, atmospheric
pressure MALDI-MS measurements using 3-CF3-BTD as a matrix also detected
dopamine.
PMID- 27506720
TI - Fast Determination of Toxic Arsenic Species in Food Samples Using Narrow-bore
High-Performance Liquid-Chromatography Inductively Coupled Plasma Mass
Spectrometry.
AB - A new method for the speciation analysis of arsenic in food using narrow-bore
high-performance liquid-chromatography inductively coupled plasma mass
spectrometry (HPLC-ICP-MS) has been developed. Fast separation of arsenite,
arsenate, monomethylarsonic acid and dimethylarsinic acid was carried out in 7
min using an anion-exchange narrow-bore Nucleosil 100 SB column and 12 mM
ammonium dihydrogen phosphate of pH 5.2 as the mobile phase, at a flow rate of
0.3 mL min(-1). A PFA-ST micronebulizer jointed to a cyclonic spray chamber was
used for HPLC-ICP-MS coupling. Compared with standard-bore HPLC-ICP-MS, the new
method has provided higher sensitivity, reduced mobile-phase consumption, a lower
matrix plasma load and a shorter analysis time. The achieved instrumental limits
of detection were in the 0.3 - 0.4 ng As mL(-1) range, and the precision was
better than 3%. The arsenic compounds were efficiently (>80%) extracted from
various food samples using a 1:5 methanol/water solution, with additional
ultrasonic treatment for rice products. The applicability of this method was
demonstrated by the analysis of several samples, such as seafood (fish, mussels,
shrimps, edible algae) and rice-based products (Jasmine and Arborio rice,
spaghetti, flour, crackers), including three certified reference materials.
PMID- 27506722
TI - Retrospective Descriptive Study of an Intensive Care Unit at a Ugandan Regional
Referral Hospital.
AB - BACKGROUND: We describe delivery and outcomes of critical care at Mbarara
Regional Referral Hospital, a Ugandan secondary referral hospital serving a
large, widely dispersed rural population. METHODS: Retrospective observational
study of ICU admissions was performed from January 2008 to December 2011.
RESULTS: Of 431 admissions, 239 (55.4 %) were female, and 142 (33.2 %) were
children (<18 years). The median length of stay was 2 (IQR 1-4) days, with 365
patients (85 %) staying less than 8 days. Indications for admission were surgical
49.3 % (n = 213), medical/pediatric 27.4 % (n = 118), or
obstetrical/gynecological 22.3 % (n = 96). The overall mortality rate was 37.6 %
(162/431) [adults 39.3 % (n = 113/287), children 33.5 % (n = 48/143), unspecified
age 100 % (n = 1/1)]. Of the 162 deaths, 76 (46.9 %) occurred on the first, 20
(12.3 %) on the second, 23 (14.2 %) on the third, and 43 (26.5 %) on a subsequent
day of admission. Mortality rates for common diagnoses were surgical abdomen 31.9
% (n = 29/91), trauma 45.5 % (n = 30/66), head trauma 59.6 % (n = 28/47), and
poisoning 28.6 % (n = 10/35). The rate of mechanical ventilation was 49.7 % (n =
214/431). The mortality rate of ventilated patients was 73.5 % (n = 119/224). The
multivariate odd ratio estimates of mortality were significant for ventilation
[aOR 6.15 (95 % CI 3.83-9.87), p < 0.0001] and for length of stay beyond seven
days [aOR 0.37 (95 % CI 0.19-0.70), p = 0.0021], but not significant for decade
of age [aOR 1.06 (95 % CI 0.94-1.20), p = 0.33], gender [aOR 0.61(95 % CI 0.38
0.99), p = 0.07], or diagnosis type [medical vs. surgical aOR 1.08 (95 % CI 0. 63
1.84), medical vs. obstetric/gynecology aOR 0.73 (95 % CI 0.37-1.43), p = 0.49].
CONCLUSIONS: The ICU predominantly functions as an acute care unit for critically
ill young patients, with most deaths occurring within the first 48 h of
admission. Expansion of critical care capacity in low-income countries should be
accompanied by measurement of the nature and impact of this intervention.
PMID- 27506723
TI - A New Prediction Model for Patient Satisfaction After Total Knee Arthroplasty.
AB - BACKGROUND: Total knee arthroplasty (TKA) is a proven and cost-effective
treatment for osteoarthritis. Despite the good to excellent long-term results,
some patients remain dissatisfied. Our study aimed at establishing a predictive
model to aid patient selection and decision-making in TKA. METHODS: Using data
from our prospective arthroplasty outcome database, 113 patients were included.
Preoperatively and postoperatively, the patients completed 107 questions in 5
questionnaires: Knee Injury and Osteoarthritis Outcome Score, Oxford Knee Score,
Pain Catastrophizing Scale, Euroqol questionnaire, and Knee Scoring System.
First, outcome parameters were compared between the satisfied and dissatisfied
group. Second, we developed a new prediction tool using regression analysis. Each
outcome score was analyzed with simple regression. Subsequently, the predictive
weight of individual questions was evaluated applying multiple linear regression.
Finally, 10 questions were retained to construct a new prediction tool. RESULTS:
Overall satisfaction rate in this study was found to be 88%. We identified a
significant difference between the satisfied and dissatisfied group when looking
at the preoperative questionnaires. Dissatisfied patients had more preoperative
symptoms (such as stiffness), less pain, and a lower quality of life. They were
more likely to ruminate and had a lower preoperative Knee Scoring System
satisfaction score. The developed prediction tool consists of 10 simple but
robust questions. Sensitivity was 97% with a positive-predictive value of 93%.
CONCLUSIONS: Based upon preoperative parameters, we were able to partially
predict satisfaction and dissatisfaction after TKA. After further validation,
this new prediction tool for patient satisfaction following TKA may allow
surgeons and patients to evaluate the risks and benefits of surgery on an
individual basis and help in patient selection.
PMID- 27506724
TI - Socioeconomic Risk Adjustment Models for Reimbursement Are Necessary in Primary
Total Joint Arthroplasty.
AB - BACKGROUND: Alternative payment models, such as bundled payments, aim to control
rising costs for total knee arthroplasty (TKA) and total hip arthroplasty (THA).
Without risk adjustment for patients who may utilize more resources, concerns
exist about patient selection and access to care. The purpose of this study was
to determine whether lower socioeconomic status (SES) was associated with
increased resource utilization following TKA and THA. METHODS: Using the Michigan
Arthroplasty Registry Collaborative Quality Initiative database, we reviewed a
consecutive series of 4168 primary TKA and THA patients over a 3-year period. We
defined lowest SES based upon the median household income of the patient's ZIP
code. Demographics, medical comorbidities, length of stay, discharge destination,
and readmission rates were compared between patients of lowest SES and higher
SES. RESULTS: Patients in the lowest SES group had a longer hospital length of
stay (2.79 vs 2.22 days, P < .001), were more likely to be discharged to a
rehabilitation facility (27% vs 18%, P < .001), and be readmitted to the hospital
within 90 days (11% vs 8%, P = .002) than the higher SES group. Multivariate
analysis revealed that lowest SES was an independent risk factor for all 3
outcome variables (all P < .001). CONCLUSION: Patients in the lowest SES group
utilize more resources in the 90-day postoperative period. Therefore, risk
adjustment models, including SES, may be necessary to fairly compensate hospitals
and surgeons and to avoid potential problems with access to joint arthroplasty
care.
PMID- 27506725
TI - Total Knee Arthroplasty After Failed Unicompartmental Knee Arthroplasty. Clinical
Results, Radiologic Findings, and Technical Tips.
AB - BACKGROUND: The loss of anatomic references and bone stock turns unicompartmental
knee arthroplasty (UKA) revision surgery difficult, and according to some
authors, it is technically as challenging as a total knee arthroplasty (TKA)
revision surgery. METHODS: A retrospective review of 559 Oxford medial UKA was
performed between 2007 and 2013. Nineteen knees were revised to TKA for reasons
other than infection, most commonly for osteoarthritis progression. RESULTS: The
most frequent cause of failure in our series was osteoarthritis progression (10
cases, 52.63%). In 15 patients (78.95%), tibial stems were needed, and in 10
(55.5%), metallic blocks for augmentation of tibial plateau were used.
Postoperative radiographic studies showed a correct implant alignment, preserving
adequate joint line (24.8 mm), and patellar (1.1 mm) height (according to Insall
Salvati). After a mean follow-up of 21 months (range 6-51) mean values of 78.8
(standard deviation [SD] = 16.8) and 62.3 (SD = 19.6) were obtained for the
physical and mental scores of the Knee Society Score test. In the SF-36 tests
mean values of 45.2 (SD = 7.6) and 53 (SD = 5.2) were obtained for the physical
and mental scores respectively. In one case, a varus/valgus instability occurred
intraoperatively and it required revision with a prosthesis with higher
constriction. No thromboembolic or infectious events were observed during
postoperative follow-up. CONCLUSION: Following a standardized technique, UKA
revision surgery can be achieved with TKA in almost every case despite bone stock
loss and lack of anatomic landmarks.
PMID- 27506726
TI - Highly conductive, printable pastes from capillary suspensions.
AB - We have used the capillary suspension phenomenon to design conductive pastes for
printed electronic applications, such as front side metallization of solar cells,
without non-volatile, organic additives that often deteriorate electrical
properties. Adding a small amount of a second, immiscible fluid to a suspension
creates a network of liquid bridges between the particles. This capillary force
controlled microstructure allows for tuning the flow behavior in a wide range.
Yield stress and low-shear viscosity can be adjusted such that long-term
stability is provided by inhibiting sedimentation, and, even more importantly,
narrow line widths and high aspect ratios are accessible. These ternary mixtures,
called capillary suspensions, exhibit a strong degree of shear thinning that
allows for conventional coating or printing equipment to be used. Finally, the
secondary fluid, beneficial for stability and processing of the wet paste,
completely evaporates during drying and sintering. Thus, we obtained high purity
silver and nickel layers with a conductivity two times greater than could be
obtained with state-of-the-art, commercial materials. This revolutionary concept
can be easily applied to other systems using inorganic or even organic conductive
particles and represents a fundamental paradigm change to the formulation of
pastes for printed electronics.
PMID- 27506727
TI - Effective axillary malodour reduction by polyquaternium-16-containing deodorants.
AB - OBJECTIVE: Worldwide, individuals apply deodorants to combat malodour formation
originating from the axillary vault. Considering the globally increasing demand
for efficacious, safe deodorants, we investigated the antimicrobial effectiveness
of a polymeric quaternary ammonium compound (PQ-16) as a new active in a roll-on
formulation against microbial growth and axillary malodour. METHODS: We utilized
an in vivo microbiological assessment to determine antimicrobial effects of the
PQ-16-containing deodorant formulation (DEO1) (i) in comparison with a
commercially available deodorant roll-on claiming a 24-h protection against body
odour (DEO2) and (ii) in comparison with a roll-on containing the same
formulation as DEO1 but comprising aluminium chlorohydrate instead of PQ-16
(DEO3) 1, 4, 8, 24 and 48 h after treatment. Also, the axillary malodour
intensity 24 and 48 h after application of deodorants was investigated in a
controlled in vivo study performed by a trained sniffer panel using direct
sniffing. RESULTS: Treatment with DEO1 in comparison with application of DEO2
significantly reduced the log 10 bacterial count at all points in time. After 24
and 48 h, sniffers rated malodour production in the DEO1-treated axillae
significantly lower than in the DEO2-treated armpits. Application of DEO1 in
comparison with DEO3 decreased the log 10 bacterial count after 1, 4, 8 and 24 h
(significant for 4 and 8 h). After 48 h, the log 10 bacterial count showed
similar values for both DEO1 and DEO3. The sniffer panel reported no significant
differences between axillary malodour in DEO1-treated compared to DEO3-treated
armpits after 24 and 48 h. CONCLUSION: We identified polyquaternium-16 (PQ-16,
copolymers of 1-vinyl-2-pyrrolidone and 1-vinyl-3-methylimidazolium chloride) as
a highly effective deodorant active. Results showed that a newly developed PQ-16
containing deodorant roll-on formulation (i) significantly reduced axillary
malodour 24 and 48 h after treatment, (ii) significantly decreased the amount of
axillary bacteria, (iii) compared to a commercially available deodorant claiming
a 24-h odour protection significantly lowered axillary malodour 24 h and 48 h
after application, and (iv) was well tolerated by the study population. PQ-16
represents an innovative and skin-friendly deodorant active.
PMID- 27506728
TI - Subclinical hypothyroidism causing hypertension in pregnancy.
AB - This is a case of a 25-year-old primigravida who was referred to the hypertension
specialist for elevated blood pressures. The patient had an elevated thyroid
stimulating hormone with normal free thyroxine (T4) levels and was positive for
thyroid peroxidase antibodies resulting in a diagnosis of subclinical
hypothyroidism. The patient was successfully treated with levothyroxine which
normalized the blood pressure without the need for antihypertensive treatment.
This case illustrates a cause of secondary hypertension that is not always
considered in the differential diagnosis of a patient with hypertension in
pregnancy.
PMID- 27506729
TI - Acute metabolic amplification of insulin secretion in mouse islets: Role of
cytosolic acetyl-CoA.
AB - OBJECTIVE: Stimulation of the beta-cell metabolism by glucose and other fuels
triggers insulin release by enhancing the mitochondrial ATP production and
acutely amplifies the secretory response by increase in mitochondrial export of
metabolites. We aimed to narrow down the uniform final reaction steps mediating
fuel-induced acute amplification of insulin secretion. MATERIAL/METHODS: Insulin
secretion and metabolic parameters were measured in isolated mouse islets exposed
to the sulfonylurea glipizide in high concentration (closing all ATP-sensitive
K(+) channels) during the entire experiment. Fuel-induced effects were examined
after treating the islets for one hour with medium devoid of fuels. This
experimental design prevented acute amplification, but only when glucose was the
sole fuel. RESULTS: Strong amplification of insulin secretion by alpha
ketoisocaproate or glucose combined with alpha-ketoisovalerate (supplying
mitochondrial oxaloacetate) was abolished within 14min after transition to medium
devoid of fuels. After transition from medium containing glucose plus alpha
ketoisovalerate to medium containing solely glucose or alpha-ketoisovalerate,
amplification (strong or weak, respectively) occurred until the end of the
experiment. Glucose (alone or combined with alpha-ketoisovalerate) increased the
total acetyl-CoA content as intensely as alpha-ketoisocaproate. Low
concentrations of alpha-ketoisovalerate or alpha-ketoisocaproate were sufficient
for saturation of acetyl-CoA increase, but caused no or only weak amplification,
respectively. No acetyl-CoA increases occurred in the absence of glipizide.
CONCLUSIONS: Glucose and other fuels regulate acute amplification of insulin
secretion by controlling the supply of acetyl-CoA to the beta-cell cytosol.
Cytosolic acetyl-CoA does not amplify by serving as substrate for syntheses of
metabolic intermediates, but amplifies by acting as substrate for cytosolic
protein acetylation.
PMID- 27506730
TI - Deep subcutaneous adipose tissue lipid unsaturation associates with
intramyocellular lipid content.
AB - BACKGROUND: Obese twins have lower saturated and higher long-chain
polyunsaturated fatty acids (FA) in subcutaneous adipose tissue (SAT) compared to
their lean monozygotic (MZ) co-twin. Whether this holds for metabolically
distinct deep (DSAT) and superficial (SSAT) depots is unknown. Here we use non
invasive magnetic resonance spectroscopy (MRS) to measure the FA unsaturation in
body mass index (BMI) discordant MZ twins in DSAT and SSAT and their relationship
to ectopic fat content and body fat distribution. The main finding is further
confirmed in an independent cohort using standardized measurement times. METHODS:
MRS and magnetic resonance imaging were used to measure DSAT and SSAT
unsaturation and their relationship to intramyocellular lipids (IMCL),
hepatocellular lipids (HCL) and the amount of subcutaneous (SAT) and visceral
adipose tissue (VAT) in 16 pairs of healthy monozygotic twins (MZ) discordant for
BMI. A second independent cohort of 12 healthy volunteers was used to measure
DSAT unsaturation and IMCL with standardized measurement time. One volunteer also
underwent repeated random measurements of DSAT unsaturation and IMCL. RESULTS: In
accordance with biopsy studies SSAT unsaturation was higher in the heavier twins
(15.2+/-1.0% vs. 14.4+/-1.5%, P=0.024) and associated with SAT volume (R=0.672,
P=0.001). DSAT unsaturation did not differ between twins (11.4+/-0.8 vs. 11.0+/
1.0, P=0.267) and associated inversely with IMCL content (R=-0.462, P=0.001). The
inverse association between DSAT unsaturation and IMCL was also present in the
participants of the second cohort (R=-0.641, P=0.025) and for the repeated
sampling at random of one person (R=-0.765, P=0.027). CONCLUSIONS: DSAT and SSAT
FA unsaturation shows distinct associations with obesity and IMCL in MZ twins,
reflecting compartment-specific metabolic activities. The FA unsaturation in the
DSAT depot associates inversely with IMCL content, which raises the possibility
of cross talk between the DSAT depot and the rapid turnover IMCL depot.
PMID- 27506732
TI - Apolipoprotein D deficiency is associated to high bone turnover, low bone mass
and impaired osteoblastic function in aged female mice.
AB - BACKGROUND: Apolipoprotein D (ApoD) is a member of the lipocalin family known to
transport small hydrophobic ligands. A major site of ApoD expression in mice is
the central nervous system where evidence suggests that it plays a protective
role. Gene expression of ApoD was reported in bone-forming osteoblasts but its
impact on bone metabolism remains undocumented. METHODS: We compared basic bone
parameters of ApoD(-/-) (null) and transgenic (tg) mice to wild-type (wt)
littermates through microCT and histochemistry, as well as ApoD expression and
secretion in osteoblasts under various culture conditions through real-time PCR
and immunoblotting. RESULTS: ApoD-null females displayed progressive bone loss
with aging, resulting in a 50% reduction in trabecular bone volume and a 23%
reduction in cortical bone volume by 9months of age. Only cortical bone volume
was significantly reduced in ApoD-null males by an average of 24%. Histochemistry
indicated significantly higher osteoblast surface and number of osteoclasts in
femora from ApoD-null females. ApoD gene expression was confirmed in primary
cultures of bone marrow mesenchymal cells (MSC), with higher expression levels in
MSC from females compared to males. ApoD-null MSC exhibited impaired
proliferation and differentiation potentials. Moreover, exogenous ApoD partially
rescued the osteogenic potential of null MSC, which were shown to readily uptake
the protein from media. ApoD expression was upregulated under low proliferation
conditions, by contact inhibition and osteoblastic differentiation in MC3T3-E1
osteoblast-like cells. CONCLUSION: Our results indicate that ApoD influences bone
metabolism in mice in a gender-specific manner, potentially through an auto
/paracrine pathway.
PMID- 27506731
TI - Endoplasmic reticulum stress in obesity and obesity-related disorders: An
expanded view.
AB - The endoplasmic reticulum (ER) is most notable for its central roles in calcium
ion storage, lipid biosynthesis, and protein sorting and processing. By virtue of
its extensive membrane contact sites that connect the ER to most other organelles
and to the plasma membrane, the ER can also regulate diverse cellular processes
including inflammatory and insulin signaling, nutrient metabolism, and cell
proliferation and death via a signaling pathway called the unfolded protein
response (UPR). Chronic UPR activation has been observed in liver and/or adipose
tissue of dietary and genetic murine models of obesity, and in human obesity and
non-alcoholic fatty liver disease (NAFLD). Activation of the UPR in obesity and
obesity-related disorders likely has two origins. One linked to classic ER stress
involving the ER lumen and one linked to alterations to the ER membrane
environment. This review discusses both of these origins and also considers the
role of post-translational protein modifications, such as acetylation and
palmitoylation, and ER-mitochondrial interactions to obesity-mediated impairments
in the ER and activation of the UPR.
PMID- 27506733
TI - Influences of body size phenotype on the incidence of gestational diabetes
needing prescription; analysis by Korea National Health Insurance (KNHI) claims
and the National Health Screening Examination (NHSE) database.
AB - OBJECTIVES: Although growing evidence has emphasized the pivotal role of
metabolic status irrespective of body mass index (BMI), there has been no study
to examine the association of body size phenotype with development of gestational
diabetes that requires treatment with oral hypoglycemic agent or insulin (GDM+T)
in primiparas. METHODS: Data from a total of 216,961 women who participated in
the National Health Screening Examination (NHSE) between January 2007 and
December 2011 and delivered their first babies within two years of the NHSE were
analyzed. Body size phenotypes were classified according to body mass index (BMI)
and the presence/absence of metabolic syndrome according to the results of the
NHSE. GDM+T was identified using the International Classification of Diseases
10th Revision (ICD-10) and prescription codes using Korea National Health
Insurance (KNHI) claims. RESULTS: Approximately 0.39% of primiparas developed
GDM+T. Compared to metabolically healthy normal weight (MHNW) women, both
metabolically unhealthy normal weight (MUNW) and metabolically healthy obese
(MHO) women had a significantly increased risk for developing GDM+T (odds ratio,
OR: 9.53, 95% confidence interval, CI: 5.64-16.09 and OR: 3.30, 95% CI: 2.56
4.25, respectively). Specifically, MUNW individuals had a significantly higher
risk of GDM+T when directly compared to MHO women even after adjusting for other
GDM risk factors (OR: 2.92, 95% CI: 1.67-5.10). Furthermore, underweight women
with metabolic syndrome showed a significantly increased frequency of GDM+T
compared to MHNW subjects (OR: 8.87, 95% CI: 1.19-66.32). CONCLUSIONS: Pre
pregnant metabolic status is critical for development of GDM+T, regardless of
their BMI. Therefore, intensive intervention for the components of metabolic
syndrome may be helpful for the prevention of GDM+T even in low or normal weight
women.
PMID- 27506735
TI - Immune therapy in type 1 diabetes mellitus - Attempts to untie the Gordian knot?
PMID- 27506734
TI - Beyond knockout: A novel homodimerization-targeting MyD88 inhibitor prevents and
cures type 1 diabetes in NOD mice.
AB - INTRODUCTION AND AIMS: Studies have reported that myeloid differentiation factor
88 (MyD88) plays an important role in the development of type 1 diabetes (T1D).
The aim of this study was to determine the effects of the self-created MyD88
inhibitor, TJ-M2010-6, in preventing and treating T1D. METHODS: Molecule docking
and co-immunoprecipitation were used to determine the suppressing capability of
TJ-M2010-6 on the homodimerization of MyD88. The preventive and therapeutic
effects of TJ-M2010-6 were tested in NOD mice. RESULTS: TJ-M2010-6 interacted
with amino acid residues of the MyD88 TIR domain and inhibited MyD88
homodimerization. Continuous administration of TJ-M2010-6 significantly reduced
the onset of diabetes during the observation period in NOD mice (36.4% vs. 80%,
P<0.01). Although the immediate TJ-M2010-6 treatment group showed a retardation
in the rise of their blood glucose level, the delayed treatment group did not
show this effect. Mechanism studies have shown that TJ-M2010-6 treatment
significantly inhibits insulitis in vivo. In vitro, TJ-M2010-6 inhibited the
maturation of DCs, leading to the suppression of T cell activation and
inflammatory cytokine secretion. CONCLUSIONS: These results demonstrated that the
strategy targeted at the innate immune system using the MyD88 inhibitor had a
profound significance in preventing and treating T1D.
PMID- 27506736
TI - Clinical correlates of sex hormones in women: The study of health in Pomerania.
AB - BACKGROUND: Despite associations of sex hormones in women with increased
cardiometabolic risk and mortality, the clinical correlates of altered sex
hormone concentrations in women are less clearly understood. We investigated a
broad range of clinical correlates of sex hormones in women from a large
population-based sample. METHODS: Data from 2560 women from two cohorts of the
Study of Health in Pomerania were used. Stepwise multivariable regression models
were implemented to investigate a broad range of behavioral, socio-demographic,
and cardiometabolic clinical correlates related to total testosterone (TT), free
testosterone (fT), androstenedione (ASD), dehydroepiandrosterone-sulfate (DHEAS),
estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG). RESULTS:
Waist circumference and BMI (beta-coefficient: -0.03; 95% CI: -0.04; 0.03) were
inversely related to SHBG, and BMI was positively related to TT (beta
coefficient: 0.005; 95% CI: 0.001; 0.009), fT, E1, and E2. Smoking was positively
related to TT (beta-coefficient: 0.04; 95% CI: 0.01; 0.06), ASD, and fT. Systolic
blood pressure (TT: beta-coefficient: 0.002; 95% CI: 0.001; 0.003), hypertension
(TT: beta-coefficient: 0.05; 95% CI: 0.003; 0.11), low-density lipoprotein (LDL)
cholesterol (TT: beta-coefficient: 0.02; 95% CI: 0.01; 0.05), and total
cholesterol (TT: beta-coefficient: -0.03; 95% CI: 0.01; 0.05) were positively
related to TT and ASD. Finally, type 2 diabetes mellitus (T2DM), and metabolic
syndrome (MetS) were positively related to fT, but inversely related to SHBG.
CONCLUSIONS: Our population-based study, with sex hormone concentrations measured
by liquid chromatography tandem mass spectrometry, revealed associations between
clinical correlates including waist circumference, smoking, cohabitation,
systolic blood pressure, cholesterol, and MetS with sex hormones. Thus, sex
hormones and SHBG may play a role in the cardiovascular risk profile of women.
PMID- 27506737
TI - Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with
thiazolidinediones: A systematic review.
AB - Thiazolidinediones (TZDs; pioglitazone and rosiglitazone) have provided promising
results in clinical trials for nonalcoholic steatohepatitis (NASH). The main
purpose of this systematic review was to summarize evidence on circulating
adiponectin levels in relation to histological changes following TZD treatment in
patients with histologically confirmed NASH. We performed a systematic search in
PubMed, Scopus and Cochrane Library. We included four studies, published between
2006 and 2012, providing data for 187 histologically confirmed NASH adult
patients (105 on TZD and 82 controls) treated for 6-12months. Significant
increase in adiponectin (80-178%) after TZD treatment was observed in all
included studies. Improvement in steatosis following treatment was observed in
all studies. A trend towards improvement in lobular inflammation was observed in
all studies after pioglitazone, but not after rosiglitazone. Trends toward
improvement in ballooning and fibrosis were observed in the two studies after
pioglitazone using either the highest doses or the longest duration of therapy.
Overall disease activity score was improved in all studies after pioglitazone,
but not after rosiglitazone. Insulin resistance and liver function tests were
also improved after treatment. Despite weight gain, circulating leptin was not
increased after treatment. In conclusion, parallel increases in circulating
adiponectin levels and histological improvement were observed in this systematic
review. These results warrant further consideration of TZDs, but even more
importantly point to a key role for novel potential treatments for NASH patients
such as the newer selective peroxisome proliferator activated receptor-gamma
modulators, which increase adiponectin without significant weight gain.
PMID- 27506738
TI - Autophagy protects human podocytes from high glucose-induced injury by preventing
insulin resistance.
AB - OBJECTIVE: Insulin resistance is correlated with the progress of albuminuria in
diabetic patients, and podocytes are crucial for maintaining the normal function
of the glomerular filtration barrier. In the present study, we aimed to
investigate the high glucose-induced insulin resistance and cell injury in human
podocytes and the putative role of autophagy in this process. METHODS: Human
podocytes were cultured in high glucose-supplemented medium and low glucose and
high osmotic conditions were used for the controls. Autophagy in the podocytes
was regulated using rapamycin or 3-methyladenine stimulation. Next, autophagy
markers including LC3B, Beclin-1, and p62 were investigated using western blot
and qPCR, and the insulin responsiveness was analyzed based on glucose uptake and
by using the phosphorylation of the insulin receptor with Nephrin as a podocyte
injury marker. RESULTS: The basal autophagy level decreased under the high
glucose conditions, which was accompanied by a decrease in the glucose uptake and
phosphorylation of the insulin receptor in the human podocytes. More
interestingly, the glucose uptake and the phosphorylation of the insulin receptor
were decreased by 3-MA stimulation and increased by rapamycin, illustrating that
the responsiveness of insulin was regulated by autophagy. The activation of
autophagy by rapamycin also ameliorated cell injury in the human podocytes.
CONCLUSIONS: The presence or activation of autophagy was found to play a
protective role in human podocytes against high glucose-induced insulin
resistance and cell injury, which indicates a novel cellular mechanism and
provides a potential therapeutic target for diabetic nephropathy (DN).
PMID- 27506739
TI - The effects of interval- vs. continuous exercise on excess post-exercise oxygen
consumption and substrate oxidation rates in subjects with type 2 diabetes.
AB - BACKGROUND: For unknown reasons, interval training often reduces body weight more
than energy-expenditure matched continuous training. We compared the acute
effects of time-duration and oxygen-consumption matched interval- vs. continuous
exercise on excess post-exercise oxygen consumption (EPOC), substrate oxidation
rates and lipid metabolism in the hours following exercise in subjects with type
2 diabetes (T2D). METHODS: Following an overnight fast, ten T2D subjects (M/F:
7/3; age=60.3+/-2.3years; body mass index (BMI)=28.3+/-1.1kg/m(2)) completed
three 60-min interventions in a counterbalanced, randomized order: 1) control
(CON), 2) continuous walking (CW), 3) interval-walking (IW - repeated cycles of
3min of fast and 3min of slow walking). Indirect calorimetry was applied during
each intervention and repeatedly for 30min per hour during the following 5h. A
liquid mixed meal tolerance test (MMTT, 450kcal) was consumed by the subjects
45min after completion of the intervention with blood samples taken regularly.
RESULTS: Exercise interventions were successfully matched for total oxygen
consumption (CW=1641+/-133mL/min; IW=1634+/-126mL/min, P>0.05). EPOC was higher
after IW (8.4+/-1.3l) compared to CW (3.7+/-1.4l, P<0.05). Lipid oxidation rates
were increased during the MMTT in IW (1.03+/-0.12mg/kg per min) and CW (0.87+/
0.04mg/kg per min) compared with CON (0.73+/-0.04mg/kg per min, P<0.01 and
P<0.05, respectively), with no difference between IW and CW. Moreover, free fatty
acids and glycerol concentrations, and glycerol kinetics were increased
comparably during and after IW and CW compared to CON. CONCLUSIONS: Interval
exercise results in greater EPOC than oxygen-consumption matched continuous
exercise during a post-exercise MMTT in subjects with T2D, whereas effects on
substrate oxidation and lipid metabolism are comparable.
PMID- 27506740
TI - Serum uric acid and mortality in chronic kidney disease: A systematic review and
meta-analysis.
AB - BACKGROUND: Studies have shown inconsistent results about the association between
serum uric acid levels and mortality in patients with chronic kidney disease
(CKD). METHODS: A systematic literature search in MEDLINE, Web of Science and
bibliographies of retrieved articles was performed to identify studies
investigating the association between serum uric acid and mortality in patients
with CKD. Pooled hazard ratios (HR) and corresponding 95% confidence intervals
(CIs) were calculated using random-effects models. RESULTS: A total of 24 studies
with 25,453 patients with CKD were included. By meta-analysis, patients with the
highest serum uric acid level were associated with a significantly higher risk
for mortality (14 studies; HR, 1.52; 95% CI, 1.33-1.73) compared with patients
with the lowest serum uric acid level. For dose-response analysis, a linear
relationship (8 studies; Pfor non-linearity=0.14) between serum uric acid levels
and risk of mortality was found. Overall, an increase of 1mg/dl in serum uric
acid level was associated with an 8% increased risk of mortality (21 studies; HR,
1.08; 95% CI, 1.04-1.11). CONCLUSIONS: Elevated serum uric acid levels are
significantly associated with risk of mortality in patients with CKD. Further
randomized controlled trials should attempt to determine whether it improves
survival to target serum uric acid in patients with CKD.
PMID- 27506741
TI - The novel mineralocorticoid receptor antagonist finerenone in diabetic kidney
disease: Progress and challenges.
PMID- 27506742
TI - Effects of lifestyle intervention on left ventricular regional myocardial
function in metabolic syndrome patients from the RESOLVE randomized trial.
AB - AIMS: The purpose of our study was to determine the effect of lifestyle
intervention on left ventricular (LV) regional myocardial function in patients
with metabolic syndrome (MetS) and investigate the relationships of the changes
in myocardial function to changes in epicardial adipose tissue (EAT),
inflammatory profile and MetS components. METHODS: Eighty-seven MetS patients
were enrolled in a 6month lifestyle intervention program based on dietary
management and increased physical activity, and compared with 44 aged and sex
matched healthy controls. MetS individuals were allocated to different groups
randomized (computer-generated randomization) on exercise modalities (high
intensity dominant resistance or aerobic training, and moderate-intensity of both
modes). EAT was measured by transthoracic echocardiography and LV longitudinal
strains and strain rates were obtained using vector velocity imaging. Blood
chemistry allowed assessments of adipocytokines (TNF-alpha: tumor necrosis factor
alpha, PAI active: active plasminogen activator inhibitor-1 and adiponectin) and
glucose tolerance markers. RESULTS: Regardless of exercise training modalities,
lifestyle intervention improved significantly LV strains and strain rates
(p<0.001) as well as metabolic and inflammatory profiles. Stepwise multiple
regression analyses revealed EAT (beta=0.73, p<0.01), log adiponectin (beta=
0.13, p<0.05) and log TNF-alpha (beta=0.15, p<0.05) as independent predictors of
LV longitudinal strain (R(2)=0.74, p<0.001) while myocardial function improvement
consecutive to lifestyle intervention was explained by EAT changes only
(R(2)=0.54, p<0.001). CONCLUSION: The mechanisms through which regional
myocardial function is impaired in MetS and improved consecutive to intervention
involved EAT, possibly via paracrine effects of adipocytokines. EAT should be
considered as a future therapeutic target of interest in the treatment of
metabolic-related cardiac diseases.
PMID- 27506743
TI - Imbalance of plasma amino acids, metabolites and lipids in patients with
lysinuric protein intolerance (LPI).
AB - BACKGROUND: Lysinuric protein intolerance (LPI [MIM 222700]) is an aminoaciduria
with defective transport of cationic amino acids in epithelial cells in the small
intestine and proximal kidney tubules due to mutations in the SLC7A7 gene. LPI is
characterized by protein malnutrition, failure to thrive and hyperammonemia. Many
patients also suffer from combined hyperlipidemia and chronic kidney disease
(CKD) with an unknown etiology. METHODS: Here, we studied the plasma metabolomes
of the Finnish LPI patients (n=26) and healthy control individuals (n=19) using a
targeted platform for analysis of amino acids as well as two analytical platforms
with comprehensive coverage of molecular lipids and polar metabolites. RESULTS:
Our results demonstrated that LPI patients have a dichotomy of amino acid
profiles, with both decreased essential and increased non-essential amino acids.
Altered levels of metabolites participating in pathways such as sugar, energy,
amino acid and lipid metabolism were observed. Furthermore, of these metabolites,
myo-inositol, threonic acid, 2,5-furandicarboxylic acid, galactaric acid, 4
hydroxyphenylacetic acid, indole-3-acetic acid and beta-aminoisobutyric acid
associated significantly (P<0.001) with the CKD status. Lipid analysis showed
reduced levels of phosphatidylcholines and elevated levels of triacylglycerols,
of which long-chain triacylglycerols associated (P<0.01) with CKD. CONCLUSIONS:
This study revealed an amino acid imbalance affecting the basic cellular
metabolism, disturbances in plasma lipid composition suggesting hepatic steatosis
and fibrosis and novel metabolites correlating with CKD in LPI. In addition, the
CKD-associated metabolite profile along with increased nitrite plasma levels
suggests that LPI may be characterized by increased oxidative stress and
apoptosis, altered microbial metabolism in the intestine and uremic toxicity.
PMID- 27506744
TI - Role of metabolism in neurodegenerative disorders.
AB - Along with the increase in life expectancy over the last century, the prevalence
of age-related disorders, such as neurodegenerative diseases continues to rise.
This is the case of Alzheimer's, Parkinson's, Huntington's diseases and Multiple
sclerosis, which are chronic disorders characterized by neuronal loss in motor,
sensory or cognitive systems. Accumulating evidence has suggested the presence of
a strong correlation between metabolic changes and neurodegeneration. Indeed
epidemiologic studies have shown strong associations between obesity, metabolic
dysfunction, and neurodegeneration, while animal models have provided insights
into the complex relationships between these conditions. In this context,
hormones such as leptin, ghrelin, insulin and IGF-1 seem to play a key role in
the regulation of neuronal damage, toxic insults and several other
neurodegenerative processes. This review aims to presenting the most recent
evidence supporting the crosstalk linking energy metabolism and
neurodegeneration, and will focus on metabolic manipulation as a possible
therapeutic tool in the prevention and treatment of neurodegenerative diseases.
PMID- 27506745
TI - Lipid phenotypes in patients with nonalcoholic fatty liver disease.
AB - OBJECTIVE: There has been conflicting evidence regarding the role of single lipid
species in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed
to explore the associations between dyslipidemia phenotypes (combinations of
lipid parameters) and the risk of NAFLD. METHODS: We conducted a cross-sectional
analysis using a cohort of 9560 apparently healthy Chinese adults who underwent
comprehensive health checkups including abdominal ultrasonography. RESULTS: Of
3709 participants with NAFLD, 41.8% were classified as normolipemia (NL), 3.8% as
combined hyperlipidemia, 3.2% as hypercholesterolemia, 17.7% as dyslipidemia of
metabolic syndrome (MetS), 10.2% as isolated low high-density lipoprotein
cholesterol (HDL-C), and 23.3% as isolated hypertriglyceridemia. The
multivariable-adjusted odds ratios (ORs) (with 95% confidence intervals) for
NAFLD in those with combined hyperlipidemia, those with hypercholesterolemia,
those with MetS dyslipidemia, those with low HDL-C, and those with
hypertriglyceridemia compared with those with NL were 4.79 (3.19-7.20), 1.26
(0.94-1.69), 3.31 (2.74-3.99), 1.13 (0.95-1.34), and 2.63 (2.26-3.08),
respectively. The associations between combined hyperlipidemia, MetS
dyslipidemia, or hypertriglyceridemia and risk of NAFLD were consistently seen in
various evaluated subgroups. The interactions between lipid phenotypes and sex,
body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), or uric
acid (UA) were not significant for NAFLD (all P>0.05). CONCLUSIONS: There were
diverse dyslipidemia phenotypes in patients with NAFLD. Combined hyperlipidemia,
MetS dyslipidemia, and hypertriglyceridemia were strongly and independently
associated with increased risk of NAFLD. Gender, BMI, BP, FPG, and UA status did
not modify the associations between dyslipidemia phenotypes and NAFLD.
PMID- 27506746
TI - Validation of a metabolite panel for early diagnosis of type 2 diabetes.
AB - BACKGROUND: Accurate, early diagnosis of type 2 diabetes (T2D) would enable more
effective clinical management and a reduction in T2D complications. Therefore, we
sought to identify plasma metabolite and protein biomarkers that, in combination
with glucose, can better predict future T2D compared with glucose alone. METHODS:
In this case-control study, we used plasma samples from the Bavarian Red Cross
Blood Transfusion Center study (61 T2D cases and 78 non-diabetic controls) for
discovering T2D-associated metabolites, and plasma samples from the Personalized
Medicine Research Project in Wisconsin (56 T2D cases and 445 non-diabetic
controls) for validation. All samples were obtained before or at T2D diagnosis.
We tested whether the T2D-associated metabolites could distinguish incident T2D
cases from controls, as measured by the area under the receiver operating
characteristic curve (AUC). Additionally, we tested six metabolic/pro
inflammatory proteins for their potential to augment the ability of the
metabolites to distinguish cases from controls. RESULTS: A panel of 10
metabolites discriminated better between T2D cases and controls than glucose
alone (AUCs: 0.90 vs 0.87; p=2.08*10(-5)) in Bavarian samples, and associations
between these metabolites and T2D were confirmed in Wisconsin samples. With use
of either a Bayesian network classifier or ridge logistic regression, the
metabolites, with or without the proteins, discriminated incident T2D cases from
controls marginally better than glucose in the Wisconsin samples, although the
difference in AUCs was not statistically significant. However, when the
metabolites and proteins were added to two previously reported T2D prediction
models, the AUCs were higher than those of each prediction model alone (AUCs:
0.92 vs 0.87; p=3.96*10(-2) and AUCs: 0.91 vs 0.71; p=1.03*10(-5), for each
model, respectively). CONCLUSIONS: Compared with glucose alone or with previously
described T2D prediction models, a panel of plasma biomarkers showed promise for
improved discrimination of incident T2D, but more investigation is needed to
develop an early diagnostic marker.
PMID- 27506747
TI - Physical exercise alleviates ER stress in obese humans through reduction in the
expression and release of GRP78 chaperone.
AB - BACKGROUND AND OBJECTIVES: Perturbation of the endoplasmic reticulum (ER)
homeostasis has emerged as one of the prominent features of obesity and diabetes.
This occurs when the adaptive unfolded protein response (UPR) fails to restore ER
function in key metabolic tissues. We previously reported increased inflammation
and impaired heat shock response (HSR) in obese human subjects that were restored
by physical exercise. Here, we investigated the status of ER stress chaperone;
glucose-regulated protein 78 (GRP78) and its downstream UPR pathways in human
obese, and their modulation by a supervised 3-month physical exercise. METHODS:
Subcutaneous adipose tissue (SAT) and blood samples were collected from non
diabetic adult human lean (n=40) and obese (n=40, at baseline and after 3months
of physical exercise). Transcriptomic profiling was used as a primary screen to
identify differentially expressed genes and it was carried out on SAT samples
using the UPR RT(2) Profiler PCR Array. Conventional RT-PCR,
immunohistochemistry, immunofluorescence, Western blot and ELISA were used to
validate the transcriptomic data. Correlation analyses with the physical,
clinical and biochemical outcomes were performed using Pearson's rank correlation
coefficient. RESULTS: Levels of GRP78 and its three downstream UPR arms;
activating transcription factor-6 (ATF6), inositol-requiring enzyme-1alpha
(IRE1alpha) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) were
increased in obese subjects. More interestingly, higher levels of circulating
GRP78 protein were found in obese compared to lean subjects which correlated
negatively with maximum oxygen uptake (VO2 Max) but positively with high
sensitivity C-reactive protein (hsCRP) and obesity indicators such as BMI,
percentage body fat (PBF) and waist circumference. GRP78 increased secretion in
obese was further confirmed in vitro using 3T3-L1 preadipocyte cells under ER
stress. Finally, we showed that physical exercise significantly attenuated the
expression and release of GRP78 with a concomitant reduction in the
phosphorylation of IRE1alpha and eukaryotic initiation factor-2alpha (eIF2alpha).
CONCLUSION: Our results suggest that physical exercise alleviates ER stress in
human obese through attenuation of GRP78 signaling network.
PMID- 27506748
TI - Functional and proteomic alterations of plasma high density lipoproteins in type
1 diabetes mellitus.
AB - OBJECTIVE: Higher HDL-cholesterol (HDL-C) is linked to lower cardiovascular risk
but individuals with type 1 diabetes mellitus (T1DM) with normal or high HDL-C
have higher cardiovascular events compared to age matched non-diabetic controls
(ND). We determined whether altered HDL functions despite having normal HDL-C
concentration may explain increased cardiovascular risk in T1DM individuals. We
also determined whether irreversible posttranslational modifications (PTMs) of
HDL bound proteins occur in T1DM individuals with altered HDL functions. METHODS:
T1DM with poor glycemic control (T1D-PC, HbA1c>=8.5%, n=15) and T1DM with good
glycemic control (T1D-GC, HbA1c<=6.6%, n=15) were compared with equal numbers of
NDs, ND-PC and ND-GC respectively, matched for age, sex and body mass index
(BMI). We measured cholesterol efflux capacity (CEC) of HDL in the serum using
J774 macrophages, antioxidant function of HDL as the ability to reverse the
oxidative damage of LDL and PON1 activity using commercially available kit. For
proteomic analysis, HDL was isolated by density gradient ultracentrifugation and
was analyzed by mass spectrometry and shotgun proteomics method. RESULTS: Plasma
HDL-C concentrations in both T1DM groups were similar to their ND. However, CEC
(%) of T1D-PC (16.9+/-0.8) and T1D-GC (17.1+/-1) were lower than their respective
ND (17.9+/-1, p=0.01 and 18.2+/-1.4, p=0.02). HDL antioxidative function also was
lower (p<0.05). The abundance of oxidative PTMs of apolipoproteins involved in
CEC and antioxidative functions of HDL were higher in T1D-PC (ApoA4, p=0.041) and
T1D-GC (ApoA4, p=0.025 and ApoE, p=0.041) in comparison with ND. Both T1D-PC and
T1D-GC groups had higher abundance of amadori modification of ApoD (p=0.002 and
p=0.041 respectively) and deamidation modification of ApoA4 was higher in T1D-PC
(p=0.025). CONCLUSIONS: Compromised functions of HDL particles in T1DM
individuals, irrespective of glycemic control, could be explained by higher
abundance of irreversible PTMs of HDL proteins. These results lend mechanistic
support to the hypothesis that HDL quality rather than quantity determines HDL
function in T1DM and suggest that measurements of concentrations of HbA1c and HDL
C are not sufficient as biomarkers of effective treatment to lower cardiovascular
risk in T1DM individuals.
PMID- 27506749
TI - Predictive ability of a simple subjective memory complaints scale for incident
dementia: Evaluation of Japan's national checklist, the "Kihon Checklist".
AB - AIM: Subjective memory complaints scales are expected to be useful for the
prediction of future cognitive decline. In Japan, the "Kihon Checklist-Cognitive
Function" (KCL-CF), which consists of three items, is used for primary screening
of high-risk older adults. However, the predictive validity of the KCL-CF remains
unknown. The aim of the present cohort study was to examine whether the KCL-CF
can predict the incidence of dementia. METHODS: Information on the KCL-CF score
(0-3 points) was collected from community-dwelling older adults (>=65 years)
through a questionnaire. Data on incident dementia were retrieved from the Long
term Care Insurance database. The Cox model and receiver operating characteristic
curve analysis were used. RESULTS: Among 13 974 participants, the 5.7-year rate
of incident dementia was 8.8%. All KCL-CF items significantly predicted the risk
of incident dementia even after adjustment for age and sex (P-trend < 0.0001). A
higher KCL-CF score was associated with a higher risk of dementia; the age- and
sex-adjusted hazard ratios (95% confidence interval) were 1.00 (reference) for a
KCL-CF score of 0 points, 1.89 (1.65-2.15) for 1 point, 3.01 (2.59-3.50) for 2
points, and 6.20 (4.87-7.90) for 3 points (P-trend < 0.0001). A cut-off score of
>=1 points had a specificity of 65.1% and a sensitivity of 60.2%, and the area
under the receiver operating characteristic curve was 0.65 (95% confidence
interval 0.63-0.66). CONCLUSIONS: The KCL-CF was able to predict incident
dementia. However, because a false-negativity rate of approximately 40% would be
expected, the KCL-CF score alone might not be sufficient for screening of
dementia incidence. Geriatr Gerontol Int 2017; 17: 1300-1305.
PMID- 27506750
TI - Palliative care for a patient with Lambert-Eaton myasthenic syndrome: role of 3,4
diaminopyridine.
AB - Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon autoimmune idiopathic or
paraneoplastic syndrome producing antibodies against voltage presynaptic calcium
channels. According to previous studies, many patients with LEMS experience
remission in both the clinical symptoms of muscle weakness and the
electrophysiologic abnormalities after successful treatment of lung SCC. However,
some patients might not respond to conventional therapy and eventually require
palliative care. Hereby, we reported a LEMS patient with advanced lung malignancy
was referred for palliative care. He was benefited from multidisciplinary
approach even with limited survival. In this case, use of 3,4-diaminopyridine
(3,4-DAP) had other roles apart from symptomatic treatment.
PMID- 27506751
TI - Superior mesenteric artery (SMA) syndrome: an unusual cause of intestinal
obstruction in palliative care.
AB - Superior mesenteric artery (SMA) syndrome is an uncommon cause of intestinal
obstruction and seldom been mentioned in palliative care. Hereby, we reported a
case of SMA syndrome who presented with symptoms of upper intestinal obstruction
in a 68-year-old patient; subsequent CT findings were classical of SMA syndrome.
The patient's history of poliomyelitis and recent significant weight loss were
the predisposing factors for SMA syndrome. It also highlights the importance of
monitoring signs and symptoms of intestinal obstruction in such patients before
considering switching to oral feeding.
PMID- 27506752
TI - Association between the age and the development of colorectal cancer in patients
with familial adenomatous polyposis: a multi-institutional study.
AB - PURPOSE: To investigate the incidence of colorectal cancer among familial
adenomatous polyposis (FAP) patients by phenotype using the latest modalities.
METHODS: We collected data on 303 patients who underwent surgery for FAP at one
of 23 institutions between 2000 and 2012. The incidence of colorectal cancer was
investigated by phenotype. RESULTS: Colorectal cancer was diagnosed in 115 (38.0
%) of the 303 patients. Overall, colorectal cancer with the attenuated, sparse,
and profuse phenotypes was diagnosed at 30, 31, and 28 years of age,
respectively, in 10 % of the patients and at 59, 48, and 41 years of age,
respectively, in 50 % of the patients (P = 0.013). The patients with colorectal
cancer were older than those without colorectal cancer for all phenotypes. The
optimal cut-off age for predicting the development of colorectal cancer in the
attenuated, sparse, and profuse phenotypes was 46, 31, and 27 years,
respectively. CONCLUSIONS: Patients with profuse and sparse phenotypes should
undergo prophylactic proctocolectomy before their mid-to-late 20 s. On the other
hand, the timing and type of surgery for patients with attenuated FAP (AFAP)
should be decided individually with reference to the colonoscopic findings.
PMID- 27506753
TI - A novel transanal tube designed to prevent anastomotic leakage after rectal
cancer surgery: the WING DRAIN.
AB - PURPOSE: We introduce a novel transanal tube (TAT), named the "WING DRAIN",
designed to prevent anastomotic leakage after rectal cancer surgery, and report
the fundamental experiments that led to its development. MATERIALS AND METHODS:
We performed the basic experiments to evaluate the effect of TATs on intestinal
decompression, the changes they make in patterns of watery fluid drainage, the
changes in their decompression effect when the extension tube connecting the TAT
to the collection bag fills with watery drainage fluid, and the variations in
intestinal contact and crushing pressure made by some types of TAT. RESULTS: Any
type of TAT contributed to decompression in the intestinal tract. Watery drainage
commenced from when the water level first rose to the hole in the tip of drain.
The intestinal pressure increased with the length of the vertical twist in an
extension tube. The crushing pressures of most types of TAT were high enough to
cause injury to the intestine. CONCLUSIONS: We resolved the problems using an
existing TAT for the purpose of intestinal decompression and by creating the
first specialized TAT designed to prevent anastomotic leakage after rectal cancer
surgery in Japan.
PMID- 27506754
TI - Short- and long-term results of radial artery and saphenous vein grafts in the
right coronary system: a propensity-matched study.
AB - PURPOSE: The selection of optimal grafts for the right coronary artery remains
controversial. This study aims to evaluate the short- and long-term results of
radial artery (RA) grafts and saphenous vein grafts (SVGs) to the right coronary
artery. METHODS: We reviewed, retrospectively, isolated coronary artery bypass
grafts, placed between 1997 and 2007, and compared the long-term results of
patients who received RA (n = 110) grafts with those of patients who received
SVGs (n = 264) using propensity-score matching for risk. The preoperative
predictors of graft occlusion were investigated on a per case basis. RESULTS:
Superior survival was noted in the unmatched RA group, but late outcomes after
propensity-score matching yielded 91 patient pairs that were similar in the two
groups. Graft failure was not correlated with mortality, but showed strong
correlation with cardiac events in all patients. The predictors of graft
occlusion in the RA group were mild proximal stenosis and low indexing glomerular
filtration rates for body surface area, whereas those in the SVG were female
gender and off-pump coronary artery bypass grafting. CONCLUSIONS: There were no
significant differences in long-term outcomes between the RA and SVG groups.
Predictors of graft occlusion differed between the groups. Notably, renal
dysfunction impaired radial patency, emphasizing the importance of careful graft
selection.
PMID- 27506755
TI - Whole blood microRNAs as a prognostic classifier for acute respiratory distress
syndrome 28-day mortality.
PMID- 27506756
TI - Ten key points about ICU palliative care.
PMID- 27506759
TI - Corrigendum.
PMID- 27506757
TI - Impaired executive control and reward circuit in Internet gaming addicts under a
delay discounting task: independent component analysis.
AB - This study utilized independent component analysis to explore the abnormal
functional connectivity (FC) in male participants with Internet gaming disorder
(IGD). Functional magnetic resonance imaging and behavioral data were collected
from 21 healthy controls (HC) and 18 IGD patients when they were performing a
delay discounting task. Behavioral results revealed that the IGD patients showed
higher delay discounting rates than HC. Two networks were found to be associated
with IGD: (1) the executive control network containing the anterior cingulate
cortex and the medial and superior frontal gyrus, and (2) the basal ganglia
network containing the lentiform nucleus. Comparing to HC, IGD exhibited stronger
FC when selecting small and now options. In addition, the delay discounting rates
were positively correlated with the modulation of the two networks and the
reaction time. The results suggested that the IGD patients have enhanced
sensitivity to reward and decreased ability to control their impulsivity
effectively, which leads to myopic decision making.
PMID- 27506760
TI - Clinical and endocrine characteristics and genetic analysis of Korean children
with McCune-Albright syndrome: a retrospective cohort study.
AB - BACKGROUND: McCune-Albright syndrome (MAS) is a rare disease defined by the triad
of fibrous dysplasia (FD), cafe au lait spots, and peripheral precocious puberty
(PP). Because of the rarity of this disease, only a few individuals with MAS have
been reported in Korea. We describe the various clinical and endocrine
manifestations and genetic analysis of 14 patients with MAS in Korea. METHODS:
Patients' clinical data-including peripheral PP, FD, and other endocrine problems
were reviewed retrospectively. In addition, treatment experiences of letrozole in
five patients with peripheral PP were described. Mutant enrichment with 3'
modified oligonucleotides - polymerase chain reaction (MEMO-PCR) was performed on
eight patients to detect mutation in GNAS using blood. MEMO-PCR is a simple and
practical method that enables the nondestructive selection and enrichment of
minor mutant alleles in blood. RESULTS: The median age at diagnosis was 5 years 2
months (range: 18 months to 16 years). Eleven patients were female, and three
were male. Thirteen patients showed FD. All female patients showed peripheral PP
at onset, and three patients subsequently developed central PP. There was a
significant decrease in estradiol levels after two years of letrozole treatment.
However, bone age was advanced in four patients. Two patients had clinical
hyperthyroidism, and two patients had growth hormone (GH) excess with pituitary
microadenoma. c.602G > A (p.Arg201His) in GNAS was detected in two patients in
blood, and c.601C > T (p.Arg201Cys) in GNAS was detected in one patient in
pituitary adenoma. CONCLUSIONS: This study described the various clinical
manifestations of 14 patients with MAS in a single center in Korea. This study
first applied MEMO-PCR on MAS patients to detect GNAS mutation. Because a broad
spectrum of endocrine manifestations could be found in MAS, multiple
endocrinopathies should be monitored in MAS patients. Better treatment options
for peripheral PP with MAS are needed.
PMID- 27506762
TI - Cash strapped CCG plans to halt non-urgent referrals.
PMID- 27506761
TI - Applied multimodal diagnostics in a case of presenile dementia.
AB - BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia in the
elderly. The possibility of disease-modifying strategies has evoked a need for
early and accurate diagnosis. To improve the accuracy of the clinical diagnosis
of AD, biomarkers like cerebrospinal fluid (CSF) and neuroimaging techniques like
magnetic resonance imaging (MRI) and positron emission tomography (PET) have been
incorporated into the diagnostic guidelines of AD. CASE PRESENTATION: In this
case report we outline in reference to one of our patients with presenile
dementia the current approaches to the diagnosis of AD. The patient was a 59-year
old woman presenting with progressive memory decline. CSF-Abeta42 was normal
while P-tau was slightly increased. FDG-PET indicated a pattern typical for AD,
amyloid-PET showed an extensive global amyloid load, and tau-PET depicted a
pronounced hippocampal tracer accumulation. The MRI scan was rated as normal at
routine diagnostics, however quantitative volumetric analysis revealed
significant atrophy especially of the parietal lobe. The combination of
biomarkers and neuroimaging techniques was therefore suggestive of an underlying
AD pathology. CONCLUSIONS: To enable early and accurate diagnosis of AD and
thereby also patient recruitment for anti-tau or anti-beta-amyloid therapeutic
trials, a combination of biomarkers and neuroimaging techniques seems useful.
PMID- 27506763
TI - Reversibly tuning the mechanical properties of a DNA hydrogel by a DNA nanomotor.
AB - By integrating a DNA motor based on an i-motif sequence that undergoes a pH
dependent conformational transition into a DNA hydrogel network, such microscopic
transition leads to a macroscopic change in mechanical properties. This strategy
allows reversible tuning of the mechanical strength of the hydrogel ranging from
250 Pa to 1000 Pa.
PMID- 27506764
TI - Coupling of mitochondrial function and skeletal muscle fiber type by a miR
499/Fnip1/AMPK circuit.
AB - Upon adaption of skeletal muscle to physiological and pathophysiological stimuli,
muscle fiber type and mitochondrial function are coordinately regulated. Recent
studies have identified pathways involved in control of contractile proteins of
oxidative-type fibers. However, the mechanism for coupling of mitochondrial
function to the muscle contractile machinery during fiber type transition remains
unknown. Here, we show that the expression of the genes encoding type I myosins,
Myh7/Myh7b and their intronic miR-208b/miR-499, parallels mitochondrial function
during fiber type transitions. Using in vivo approaches in mice, we found that
miR-499 drives a PGC-1alpha-dependent mitochondrial oxidative metabolism program
to match shifts in slow-twitch muscle fiber composition. Mechanistically, miR-499
directly targets Fnip1, an AMP-activated protein kinase (AMPK)-interacting
protein that negatively regulates AMPK, a known activator of PGC-1alpha.
Inhibition of Fnip1 reactivated AMPK/PGC-1alpha signaling and mitochondrial
function in myocytes. Restoration of the expression of miR-499 in the mdx mouse
model of Duchenne muscular dystrophy (DMD) reduced the severity of DMD Thus, we
have identified a miR-499/Fnip1/AMPK circuit that can serve as a mechanism to
couple muscle fiber type and mitochondrial function.
PMID- 27506765
TI - Combination analysis of genome-wide association and transcriptome sequencing of
residual feed intake in quality chickens.
AB - BACKGROUND: Residual feed intake (RFI) is a powerful indicator for energy
utilization efficiency and responds to selection. Low RFI selection enables a
reduction in feed intake without affecting growth performance. However, the
effective variants or major genes dedicated to phenotypic differences in RFI in
quality chickens are unclear. Therefore, a genome-wide association study (GWAS)
and RNA sequencing were performed on RFI to identify genetic variants and
potential candidate genes associated with energy improvement. RESULTS: A lower
average daily feed intake was found in low-RFI birds compared to high-RFI birds.
The heritability of RFI measured from 44 to 83 d of age was 0.35. GWAS showed
that 32 of the significant single nucleotide polymorphisms (SNPs) associated with
the RFI (P < 10(-4)) accounted for 53.01 % of the additive genetic variance. More
than half of the effective SNPs were located in a 1 Mb region (16.3-17.3 Mb) of
chicken (Gallus gallus) chromosome (GGA) 12. Thus, focusing on this region should
enable a deeper understanding of energy utilization. RNA sequencing was performed
to profile the liver transcriptomes of four male chickens selected from the high
and low tails of the RFI. One hundred and sixteen unique genes were identified as
differentially expressed genes (DEGs). Some of these genes were relevant to
appetite, cell activities, and fat metabolism, such as CCKAR, HSP90B1, and PCK1.
Some potential genes within the 500 Kb flanking region of the significant RFI
related SNPs detected in GWAS (i.e., MGP, HIST1H110, HIST1H2A4L3, OC3, NR0B2,
PER2, ST6GALNAC2, and G0S2) were also identified as DEGs in chickens with
divergent RFIs. CONCLUSIONS: The GWAS findings showed that the 1 Mb narrow region
of GGA12 should be important because it contained genes involved in energy
consuming processes, such as lipogenesis, social behavior, and immunity. Similar
results were obtained in the transcriptome sequencing experiments. In general,
low-RFI birds seemed to optimize energy employment by reducing energy expenditure
in cell activities, immune responses, and physical activity compared to eating.
PMID- 27506766
TI - A computational docking study on the pH dependence of peptide binding to HLA-B27
sub-types differentially associated with ankylosing spondylitis.
AB - A single amino acid difference (Asp116His), having a key role in a pathogenesis
pathway, distinguishes HLA-B*27:05 and HLA-B*27:09 sub-types as associated and
non-associated with ankylosing spondylitis, respectively. In this study,
molecular docking simulations were carried out with the aim of comprehending the
differences in the binding behavior of both alleles at varying pH conditions. A
library of modeled peptides was formed upon single point mutations aiming to
address the effect of 20 naturally occurring amino acids at the binding core
peptide positions. For both alleles, computational docking was applied using
Autodock 4.2. Obtained free energies of binding (FEB) were compared within the
peptide library and between the alleles at varying pH conditions. The amino acid
preferences of each position were studied enlightening the role of each on
binding. The preferred amino acids for each position of pVIPR were found to be
harmonious with experimental studies. Our results indicate that, as the pH is
lowered, the capacity of HLA-B*27:05 to bind peptides in the library is largely
lost. Hydrogen bonding analysis suggests that the interaction between the main
anchor positions of pVIPR and their respective binding pocket residues are
affected from the pH the most, causing an overall shift in the FEB profiles.
PMID- 27506767
TI - Associations between access to recreational physical activity facilities and body
mass index in Scottish adults.
AB - BACKGROUND: The aim of this country-wide study was to link individual health and
behavioural data with area-level spatial data to examine whether the body mass
index (BMI) of adults was associated with access to recreational physical
activity (PA) facilities by different modes of transport (bus, car, walking,
cycling) and the extent to which any associations were mediated by PA
participation. METHODS: Data on individual objectively-measured BMI, PA (number
of days of (a) >=20 min of moderate-to-vigorous PA, and (b) >=15 min of sport or
exercise, in previous 4 weeks), and socio-demographic characteristics were
obtained from a nationally representative sample of 6365 adults. The number of
accessible PA facilities per 1,000 individuals in each small area (data zones)
was obtained by mapping a representative list of all fixed PA facilities
throughout mainland Scotland. A novel transport network was developed for the
whole country, and routes on foot, by bike, by car and by bus from the weighted
population centroid of each data zone to each facility were calculated. Separate
multilevel models were fitted to examine associations between BMI and each of the
24 measures of accessibility of PA facilities and BMI, adjusting for age, gender,
longstanding illness, car availability, social class, dietary quality and
urban/rural classification. RESULTS: We found associations (p < 0.05) between BMI
and 7 of the 24 accessibility measures, with mean BMI decreasing with increasing
accessibility of facilities-for example, an estimated decrease of 0.015 BMI units
per additional facility within a 20-min walk (p = 0.02). None of these
accessibility measures were found to be associated with PA participation.
CONCLUSIONS: Our national study has shown that some measures of the accessibility
of PA facilities by different modes of transport (particularly by walking and
cycling) were associated with BMI; but PA participation, as measured here, did
not appear to play a part in this relationship. Understanding the multi-factorial
environmental influences upon obesity is key to developing effective
interventions to reduce it.
PMID- 27506769
TI - Erratum to: The dominance of the private sector in the provision of emergency
obstetric care: studies from Gujarat, India.
PMID- 27506768
TI - Flavihumibacter stibioxidans sp. nov., an antimony-oxidizing bacterium isolated
from antimony mine soil.
AB - A Gram-stain-positive, strictly aerobic, non-motile and rod-shaped bacterial
strain, designated YS-17T, was isolated from soil in the Lengshuijiang antimony
mine, Hunan Province, China. Comparative 16S rRNA gene sequencing analysis
clustered it with Flavihumibacter strains, and strain YS-17T was most closely
related to Flavihumibacter cheonanensis WS16T (97.2 % similarity),
Flavihumibacter petaseus T41T (96.6 %) and Flavihumibacter solisilvae 3-3T (96.5
%). The level of DNA-DNA relatedness between strain YS-17T and F. cheonanensis
JCM 19322T was 35.5+/-0.1 % (n=2). The major respiratory quinone of strain YS-17T
was menaquinone-7 and the major polar lipids were phosphatidylethanolamine, two
unidentified lipids, two unidentified amino lipids and phospholipid. The major
fatty acids (>=5 %) were iso-C15 : 0, iso-C15 : 1 G, unknown ECL 13.565, iso-C17
: 0 3-OH, C15 : 0, C16 : 1omega5c and anteiso-C15 : 0. The DNA G+C content was
47.8 mol%. Compared with other Flavihumibacter strains, strain YS-17T showed
major biophysical and biochemical differences, with the ability to hydrolyse
gelatin and to assimilate salicin and l-proline. The results demonstrated that
strain YS-17T belongs to the genus Flavihumibacter and represents a novel
species, for which the name Flavihumibacter stibioxidans sp. nov. is proposed.
The type strain is YS-17T (=CCTCC AB 2016053T=KCTC 52205T).
PMID- 27506770
TI - Inhibition of ANXA7 GTPase activity by a small molecule promotes HMBOX1
translation of vascular endothelial cells in vitro and in vivo.
AB - Homeobox containing 1 (HMBOX1) is essential for the survival of human umbilical
vein endothelial cells (HUVECs). However, the regulatory mechanism of HMBOX1
expression is still unclear. We recently found that a small molecule 6-amino-2,3
dihydro-3-hydroxymethyl-1,4-benzoxazine (ABO) directly targeted annexin A7
(ANXA7) and inhibited its GTPase activity. In addition, both HMBOX1 and ANXA7
participated in the autophagy and apoptosis of HUVECs. But, their relationship in
the regulation of HMBOX1 expression is unknown. In this study, we found that ABO
could elevate HMBOX1 at translation level through inhibiting ANXA7 GTPase
activity. ABO failed to increase HMBOX1 protein level in ANXA7-deficient HUVECs.
TGFB2 overlapping transcript 1 (TGFB2-OT1) that was increased by ABO facilitated
HMBOX1 expression by increasing La-related protein 1 (LARP1) expression.
Furthermore, the protein level of HMBOX1 was decreased under oxidized low-density
lipoprotein (oxLDL) treatment in HUVECs and in the aortic endothelium of
apolipoprotein E-deficient (apoE-/-) mice, which could be reversed by ABO in
vitro and in vivo. In conclusion, ANXA7 was an endogenous regulator of HMBOX1,
and ABO promoted HMBOX1 translation by inhibiting ANXA7 GTPase activity and
enhancing TGFB2-OT1 expression. Besides, our data suggested that HMBOX1 might be
a novel diagnostic marker and therapeutic target of atherosclerosis.
PMID- 27506771
TI - Prenatal high-dose vitamin D3 supplementation has balanced effects on cord blood
Th1 and Th2 responses.
AB - BACKGROUND: Antenatal vitamin D3 (vitD3) supplementation significantly increases
maternal and neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration, yet the
effect of an improvement in maternal-fetal vitamin D status on the neonatal
immune response is unclear. METHOD: To assess the effect of prenatal vitD3
supplementation on cord blood T cell function, healthy pregnant Bangladeshi women
(n = 160) were randomized to receive either oral 35,000 IU/week vitD3 or placebo
from 26 to 29 weeks of gestation to delivery. In a subset of participants (n =
80), cord blood mononuclear cells (CBMC) were cultured, non-adherent lymphocytes
were isolated to assess T cell cytokine responses to phytohemagglutinin (PHA) and
anti-CD3/anti-CD28 (iCD3/iCD28), measured by multiplex assay. In 12 participants,
lymphocyte gene expression profiles were analyzed by PCR array. RESULT: In
supplemented group, increased concentrations of IL-10 (P < 0.000) and TNF-alpha
(P = 0.05) with iCD3/iCD28 stimulation and IFN-gamma (p = 0.05) with PHA
stimulation were obtained compared to placebo group. No differences in the gene
expression profile were noted between the two groups. However, PHA stimulation
significantly induced the expression of genes encoding Th1 and Th2 cytokines and
down-regulated a number of genes involved in T-cell development, proliferation
and differentiation of B cells, signal transduction pathway, transcriptional
regulation and pattern recognition receptors (PRRs) in the vitamin D group (vitD
group). CONCLUSION: Third-trimester high-dose vitD3 supplementation in healthy
pregnant women had balanced effects on biomarkers of cord blood Th1 and Th2
responses. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT01126528 ).
PMID- 27506772
TI - Reply to Letter Regarding "Amplatzer Vascular Plugs Versus Coils for Embolization
of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic
Telangiectasia".
PMID- 27506773
TI - Routine Use of Surgical Retrograde Transtibial Endovascular Approach for Failed
Attempts at Antegrade Recanalization of Chronic Peripheral Artery Total
Occlusions.
AB - PURPOSE: Our aim was to describe the technical aspects and clinical outcomes of
an open surgical approach to retrograde transtibial endovascular therapy for
recanalization of chronic total occlusions (CTOs) of peripheral arteries because
of inability to acquire antegrade intravascular access across the occlusion.
MATERIALS AND METHODS: Between January 2011 and May 2014, conventional antegrade
revascularization failed in 15 limbs of 15 patients (11 males, 4 females) with
complex CTOs. The mean age of the patients was 74 years (range 48-83 years). Five
patients had severe claudication (Rutherford Category 3), and 10 patients had
critical limb-threatening ischemia (Rutherford Categories 4-5). For each of these
cases of antegrade failure, an open surgical exposure of the tibial or dorsalis
pedis artery was used to allow a safe retrograde transtibial endovascular
approach to recanalize the CTO. RESULTS: Surgical retrograde access from the
tibial artery was achieved successfully in 14 of the 15 patients. In the 14
successful retrograde endovascular approaches, surgical retrograde transtibial
access was achieved from the dorsalis pedis artery in 8 patients and from the
posterior tibial artery in 6. The average time to obtain retrograde access was 5
min (range 2-11 min). No stenosis or occlusion occurred in the tibial or dorsalis
pedis arteries used for the retrograde access sites during follow-up.
CONCLUSIONS: Routine surgical exposure can be a safe and an effective method for
retrograde transtibial access to the more proximal occluded arterial segments in
selected patients with CTO.
PMID- 27506774
TI - [Positioning therapy and early mobilization in intensive care units : Findings
from the current 2015 guidelines].
AB - The 2007 guidelines "Positioning for prophylaxis and therapy of pulmonary
disorders" were completely revised in 2015 on behalf of the German Society of
Anaesthesiology and Intensive Care Medicine. With regard to practical and
scientific relevance, early mobilization of patients in critical care has been
included in the guidelines for the first time. Furthermore, the recommendations
for prone positioning have been updated, based on current evidence in medicine
and nursing. In addition, recommendations regarding unsuitable positions that may
actually harm patients were made. As such, the flat supine position should only
be used in cases of urgent medical or nursing needs. This underlines the
importance of a moderately elevated head of bed position (20(o)-45(o)) in
mechanically ventilated patients.
PMID- 27506775
TI - [Epidemiology and mortality of extracorporeal life support in Germany between
2007 and 2014].
PMID- 27506776
TI - Spontaneous splenic rupture associated with apixaban: a case report.
AB - BACKGROUND: Spontaneous splenic rupture associated with anticoagulant use is a
rare but potentially lethal disorder. Lack of prompt recognition can be
associated with poor patient outcomes. The use of novel oral anticoagulants is
becoming more common and thus consideration of this disorder while evaluating a
patient who presents with abdominal pain while using these agents is extremely
important. This is the first reported case of spontaneous splenic rupture
associated with apixaban. CASE PRESENTATION: We describe the clinical case of an
83-year-old white man who complained of sudden severe abdominal pain 5 days into
a hospital stay for acute-on-chronic congestive heart failure and exacerbation of
chronic obstructive pulmonary disease. Neither he nor his wife reported any
significant trauma for the past 6 months prior to his admission. His medical
history included chronic atrial fibrillation treated with medications including
apixaban 2.5 mg twice daily. An urgent abdominal computed tomography scan
demonstrated a large splenic hematoma and evidence of intraperitoneal bleeding
from which he rapidly declined, developing hypovolemic shock. An emergency
splenic arteriogram displayed a patent splenic artery and an embolization was
successful in stabilizing him. Due to evidence of recurrent bleeding, an
exploratory laparotomy and splenectomy was subsequently performed the following
day. CONCLUSIONS: The diagnosis of spontaneous splenic rupture is important to
consider in a patient using apixaban who presents with abdominal pain and
associated signs of hypotension and anemia. For hemodynamically unstable
patients, prompt treatment to stop significant bleeding through splenic artery
embolization or splenectomy is warranted and may be lifesaving.
PMID- 27506777
TI - The transposable element environment of human genes is associated with histone
and expression changes in cancer.
AB - BACKGROUND: Only 2 % of the human genome code for proteins. Among the remaining
98 %, transposable elements (TEs) represent millions of sequences. TEs have an
impact on genome evolution by promoting mutations. Especially, TEs possess their
own regulatory sequences and can alter the expression pattern of neighboring
genes. Since they can potentially be harmful, TE activity is regulated by
epigenetic mechanisms. These mechanisms participate in the modulation of gene
expression and can be associated with some human diseases resulting from gene
expression deregulation. The fact that the TE silencing can be removed in cancer
could explain a part of the changes in gene expression. Indeed, epigenetic
modifications associated locally with TE sequences could impact neighboring genes
since these modifications can spread to adjacent sequences. RESULTS: We compared
the histone enrichment, TE neighborhood, and expression divergence of human genes
between a normal and a cancer conditions. We show that the presence of TEs near
genes is associated with greater changes in histone enrichment and that
differentially expressed genes harbor larger histone enrichment variation related
to the presence of particular TEs. CONCLUSIONS: Taken together, these results
suggest that the presence of TEs near genes could favor important variation in
gene expression when the cell environment is modified.
PMID- 27506778
TI - Changes in enterovirus serotype constituent ratios altered the clinical features
of infected children in Guangdong Province, China, from 2010 to 2013.
AB - BACKGROUND: Enterovirus (EV)-related hand, foot, and mouth disease/herpangina
(HFMD/HA) has been prevalent in Guangdong Province, China, since 2010. METHODS:
Clinical data for EV-related HFMD/HA inpatients admitted to the Department of
Paediatrics of Zhujiang Hospital from 2010 to 2013 were retrospectively reviewed.
The corresponding EV serotypes were also determined by reverse transcription
polymerase chain reaction or BLAST analysis of the sequenced partial lengths of
the viral protein1/5'-untranslated region. RESULTS: A total of 867 eligible
inpatients admitted during 2010-2013 were included in the study. Of these, the
serotype of the responsible EV was successfully identified in 824 cases. The
incidence of enterovirus 71 (EV71) infection amongst pediatric HFMD/HA inpatients
decreased dramatically from 55.5 % in 2010 to 8.1 % in 2013, with a similar
decrease recorded for coxsackievirus A16 (CVA16). However, the incidence of non
EV71/CVA16 infection increased from 30.0 % in 2010 to 83.8 % in 2013. We noted
that the types of infection caused by different EV serotypes varied: EV71 was
responsible for 100 % of the paralysis cases (26/26), 84.6 % of the deaths
(11/13), and 84.1 % of cases with severe central nervous system involvement
(SCNSI) (74/88); echovirus contributed to 16.4 % of the deaths (2/13) and 4.4 %
of the SCNSI cases; and coxsackievirus accounted for only 2.2 % of the SCNSI
cases (2/90). The clinical features of HFMD/HA cases varied greatly during the
time period examined, with drastic changes in the hospitalization rates (45.1,
63.7, 36.4, and 19.1 % for 2010, 2011, 2012, and 21013, respectively), mortality
rates (2.3, 0.9, 2.5, and 0.0 %, respectively), paralysis (5.1, 1.2, 5.4, and 0.0
%, respectively), SCNSI (16.8, 7.1, 12.7, and 2.2 %, respectively), and acute
respiratory infection (21.1, 22.0, 45.9, and 59.0 %, respectively). CONCLUSIONS:
The incidences of infection caused by different EV serotypes, along with the
clinical features of HFMD/HA cases, changed drastically in Guangdong Province,
China, from 2010 to 2013, with the biggest changes observed in 2013. The changed
constituent ratios of the different EV serotypes might therefore be responsible
for the differences in the observed clinical features of HFMD/HA during this
period.
PMID- 27506779
TI - Acute stroke with major intracranial vessel occlusion: Characteristics of
cardioembolism and atherosclerosis-related in situ stenosis/occlusion.
AB - Acute ischemic stroke with major intracranial vessel occlusion is commonly due to
cardioembolic or atherosclerosis-related in situ stenosis/occlusion, and
immediate identification of these subtypes is important to establish the optimal
treatment strategy. The aim of this study was to clarify the differences in
clinical presentation, radiological findings, neurological temporal courses, and
outcomes between these etiologies, which have not been fully evaluated.
Consecutive emergency patients with acute ischemic stroke were retrospectively
reviewed. Among them, patients with stroke with major intracranial vessel
occlusion were analyzed with a focus on clinical and radiological findings, and a
comparison was performed for those with cardioembolic or atherosclerosis-related
in situ stenosis/occlusion. Of 1053 patients, 80 had stroke with acute major
intracranial vessel occlusion (45 with cardioembolic and 35 with atherosclerosis
related in situ stenosis/occlusion). Interestingly, the susceptibility vessel
sign (SVS) on T2-weighted MR angiography was more frequently detected in
cardioembolic stroke (80.0%) than in atherosclerosis (in situ stenosis: 5.9%,
chronic occlusion: 14.3%). Moreover, the proximal intra-arterial signal (IAS) on
arterial spin labeling MRI and the distal IAS on fluid attenuated inversion
recovery MRI was less frequently detected in chronic occlusion (27.3% and 50.0%,
respectively) than in acute occlusion due to cardioembolic or in situ stenosis.
Multivariate regression analysis showed that the SVS was significantly related to
cardioembolism (adjusted odds ratio (OR): 21.68, P=0.004). Clinical
characteristics of acute stroke with major intracranial vessel occlusion differ
depending on the etiology. The SVS and proximal/distal IAS on MRI are useful to
distinguish between cardioembolic and atherosclerotic-related in situ
stenosis/occlusion.
PMID- 27506780
TI - Minimally invasive surgery through the interlaminar approach in the treatment of
spinal tuberculosis: A retrospective study of 31 patients.
AB - The aim of this study was to evaluate the efficacy of minimally invasive spinal
decompression combined with local chemotherapy in treating patients with
thoracic/lumbar tuberculosis (TB) and abscess compression of the spinal canal.
Clinical data of 31 patients with thoracic/lumbar TB and spinal epidural abscess,
admitted to our hospital between December 2005 and June 2014 were retrospectively
analyzed. All patients received initial conservative treatment but achieved
unsatisfactory results and then underwent minimally invasive spinal canal
decompression, focus debridement and catheter drainage through a posterior
interlaminar approach. Postoperatively, a short-course (1-2months) of local
chemotherapy was given. The patients were followed up on a regular basis. The
neurologic status was graded according to the American Spinal Injury Association
(ASIA) score system. Kyphotic deformity was evaluated using Cobb angle
measurement. Patients were followed up for an average of 37months (range: 12
96months). At the last follow-up, ASIA scores were improved in all patients, and
there was a mild increase in the Cobb angle, but satisfactory spinal
stabilization was achieved. Hepatorenal function, erythrocyte sedimentation rate
and C-reactive protein levels all returned to normal. One complication was
observed, where the patient had worsened deficit postoperatively but achieved a
satisfactory recovery (from Grade C to Grade E) one year after a second surgery.
Minimally invasive spinal canal decompression combined with local chemotherapy
appears to be an effective treatment for patients with thoracic/lumbar TB and
abscess compression in the spinal canal.
PMID- 27506781
TI - Five-year experience of 101 adult patients with moyamoya disease at a single
institution in Eastern China.
AB - This retrospective study included 101 adult moyamoya disease (MMD) patients of
whom 58 were females and 43 were males in Wenzhou, China. Clinical and diagnostic
features, surgical treatment, follow-up information and outcomes constitute this
review. The modified Rankin Scale (mRS) was used to determine the neurological
functional outcome. The Kaplan-Meier method was used to estimate recurrent stroke
and mortality risk based on drug treatment alone or in combination with
revascularization. The mean age at symptom onset was 43.3 (range, 18-64)years.
The initial symptom was either hemorrhage, ischemia or transient ischemic attack
(TIA) in 90, 6 and 5 patients, respectively. The median follow-up time in 84
patients was 26.5 (range, 6-62)months. Ten patients were treated with
revascularization. In the remaining drug-treated group, the 5-year risk of
recurrent stroke and death was 8% following onset of initial symptoms, while it
was 25% in the revascularization group. However, the difference between these two
groups was not significant (p>0.05). There was also no difference in mRS between
these two groups upon patient discharge, but in the revascularization group was
lower than that in the drug-treated group at their last follow-up (p<0.05). Adult
MMD patients were most ikely to present with hemorrhage and had a better
neurological functional outcome after revascularization than from medical
therapy. However, revascularization did not decrease the recurrent stroke
incidence or mortality risk. These results are different from those reported by
other Chinese and foreign institutions.
PMID- 27506782
TI - Decrease of aquaporin-4 and excitatory amino acid transporter-2 indicate
astrocyte dysfunction for pathogenesis of cortical degeneration in HIV-associated
neurocognitive disorders.
AB - Human immunodeficiency virus (HIV) encephalitis and degeneration of cerebral
cortex are established histopathologies of HIV-associated neurocognitive
disorders (HAND). We previously reported decreased excitatory amino acid
transporter-2 (EAAT-2) and astrocytic apoptosis in cortical degeneration using
SIVmac239 and simian-human immunodeficiency virus (SHIV)-infected macaques and
human AIDS autopsy cases. In the present study, we added highly pathogenic
SIVsm543-3-infected macaques. These animals showed similar degenerative changes
in the frontal cortex. Using 11 SIV-infected macaques, three SIVsm543-3, five
SIVmac239 and three SHIV, we compared brain pathology caused by three different
viruses and further analyzed the pathogenic process of HAND. We noticed vacuolar
changes in perivascular processes of astrocytes by electron microscopy, and
examined expression of astrocyte-specific protein aquaporin-4 (AQP4) by
immunohistochemistry. APQ4 was diffusely positive in the neuropil and
perivascular area in control brains. There was patchy or diffuse decrease of AQP4
staining in the neuropil of SIV-infected macaques, which was associated with EAAT
2 staining by double immunostaining. A quantitative analysis demonstrated
significant positive correlation between areas of AQP4 and EAAT-2. Some
astrocytes express EAAT-2 but not AQP4, and decrease of EAAT-2 expression tended
to be less than the decrease of AQP4. Active-caspase-3 immunostaining
demonstrated apoptosis of neurons and astrocytes in the area of AQP4/EAAT-2
reduction. These results suggest that AQP4 is damaged first and decrease of EAAT
2 may follow in pathogenesis of cortical degeneration. This is the first
demonstration of decrease of AQP4 and its association with EAAT-2 decrease in
AIDS brain, suggesting a role in the pathogenesis of HAND.
PMID- 27506783
TI - QnAs with Christine Jacobs-Wagner.
PMID- 27506784
TI - Bioelectronic neural pixel: Chemical stimulation and electrical sensing at the
same site.
AB - Local control of neuronal activity is central to many therapeutic strategies
aiming to treat neurological disorders. Arguably, the best solution would make
use of endogenous highly localized and specialized regulatory mechanisms of
neuronal activity, and an ideal therapeutic technology should sense activity and
deliver endogenous molecules at the same site for the most efficient feedback
regulation. Here, we address this challenge with an organic electronic
multifunctional device that is capable of chemical stimulation and electrical
sensing at the same site, at the single-cell scale. Conducting polymer electrodes
recorded epileptiform discharges induced in mouse hippocampal preparation. The
inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), was then actively
delivered through the recording electrodes via organic electronic ion pump
technology. GABA delivery stopped epileptiform activity, recorded simultaneously
and colocally. This multifunctional "neural pixel" creates a range of
opportunities, including implantable therapeutic devices with automated feedback,
where locally recorded signals regulate local release of specific therapeutic
agents.
PMID- 27506785
TI - Histone arginine methylation in cocaine action in the nucleus accumbens.
AB - Repeated cocaine exposure regulates transcriptional regulation within the nucleus
accumbens (NAc), and epigenetic mechanisms-such as histone acetylation and
methylation on Lys residues-have been linked to these lasting actions of cocaine.
In contrast to Lys methylation, the role of histone Arg (R) methylation remains
underexplored in addiction models. Here we show that protein-R-methyltransferase
6 (PRMT6) and its associated histone mark, asymmetric dimethylation of R2 on
histone H3 (H3R2me2a), are decreased in the NAc of mice and rats after repeated
cocaine exposure, including self-administration, and in the NAc of cocaine
addicted humans. Such PRMT6 down-regulation occurs selectively in NAc medium
spiny neurons (MSNs) expressing dopamine D2 receptors (D2-MSNs), with opposite
regulation occurring in D1-MSNs, and serves to protect against cocaine-induced
addictive-like behavioral abnormalities. Using ChIP-seq, we identified Src kinase
signaling inhibitor 1 (Srcin1; also referred to as p140Cap) as a key gene target
for reduced H3R2me2a binding, and found that consequent Srcin1 induction in the
NAc decreases Src signaling, cocaine reward, and the motivation to self
administer cocaine. Taken together, these findings suggest that suppression of
Src signaling in NAc D2-MSNs, via PRMT6 and H3R2me2a down-regulation, functions
as a homeostatic brake to restrain cocaine action, and provide novel candidates
for the development of treatments for cocaine addiction.
PMID- 27506786
TI - Auditory-induced neural dynamics in sensory-motor circuitry predict learned
temporal and sequential statistics of birdsong.
AB - Predicting future events is a critical computation for both perception and
behavior. Despite the essential nature of this computation, there are few studies
demonstrating neural activity that predicts specific events in learned,
probabilistic sequences. Here, we test the hypotheses that the dynamics of
internally generated neural activity are predictive of future events and are
structured by the learned temporal-sequential statistics of those events. We
recorded neural activity in Bengalese finch sensory-motor area HVC in response to
playback of sequences from individuals' songs, and examined the neural activity
that continued after stimulus offset. We found that the strength of response to a
syllable in the sequence depended on the delay at which that syllable was played,
with a maximal response when the delay matched the intersyllable gap normally
present for that specific syllable during song production. Furthermore,
poststimulus neural activity induced by sequence playback resembled the neural
response to the next syllable in the sequence when that syllable was predictable,
but not when the next syllable was uncertain. Our results demonstrate that the
dynamics of internally generated HVC neural activity are predictive of the
learned temporal-sequential structure of produced song and that the strength of
this prediction is modulated by uncertainty.
PMID- 27506787
TI - Implications for Alzheimer's disease of an atomic resolution structure of amyloid
beta(1-42) fibrils.
PMID- 27506788
TI - Glycoengineering of plants yields glycoproteins with polysialylation and other
defined N-glycoforms.
PMID- 27506789
TI - QnAs with James Allison.
PMID- 27506790
TI - Peptide- and proton-driven allosteric clamps catalyze anthrax toxin translocation
across membranes.
AB - Anthrax toxin is an intracellularly acting toxin in which sufficient information
is available regarding the structure of its transmembrane channel, allowing for
detailed investigation of models of translocation. Anthrax toxin, comprising
three proteins-protective antigen (PA), lethal factor (LF), and edema factor
translocates large proteins across membranes. Here we show that the PA
translocase channel has a transport function in which its catalytic active sites
operate allosterically. We find that the phenylalanine clamp (phi-clamp), the
known conductance bottleneck in the PA translocase, gates as either a more closed
state or a more dilated state. Thermodynamically, the two channel states have
>300-fold different binding affinities for an LF-derived peptide. The change in
clamp thermodynamics requires distant alpha-clamp and phi-clamp sites. Clamp
allostery and translocation are more optimal for LF peptides with uniform
stereochemistry, where the least allosteric and least efficiently translocated
peptide had a mixed stereochemistry. Overall, the kinetic results are in less
agreement with an extended-chain Brownian ratchet model but, instead, are more
consistent with an allosteric helix-compression model that is dependent also on
substrate peptide coil-to-helix/helix-to-coil cooperativity.
PMID- 27506791
TI - Disruption of promoter memory by synthesis of a long noncoding RNA.
AB - The yeast HO endonuclease is expressed in late G1 in haploid mother cells to
initiate mating-type interconversion. Cells can be arrested in G1 by nutrient
deprivation or by pheromone exposure, but cells that resume cycling after
nutrient deprivation or cyclin-dependent kinase (CDK) inactivation express HO in
the first cell cycle, whereas HO is not expressed until the second cycle after
release from pheromone arrest. Here, we show that transcription of a long
noncoding RNA (lncRNA) mediates this differential response. The SBF and Mediator
factors remain bound to the inactive promoter during arrest due to CDK
inactivation, and these bound factors allow the cell to remember a
transcriptional decision made before arrest. If the presence of mating pheromone
indicates that this decision is no longer appropriate, a lncRNA originating at
2700 upstream of the HO gene is induced, and the transcription machinery
displaces promoter-bound SBF, preventing HO transcription in the subsequent cell
cycle. Further, we find that the displaced SBF is blocked from rebinding due to
incorporation of its recognition sites within nucleosomes. Expressing the pHO
lncRNA in trans is ineffective, indicating that transcription in cis is required.
Factor displacement during lncRNA transcription could be a general mechanism for
regulating memory of previous events at promoters.
PMID- 27506792
TI - Crystallographic snapshots of sulfur insertion by lipoyl synthase.
AB - Lipoyl synthase (LipA) catalyzes the insertion of two sulfur atoms at the
unactivated C6 and C8 positions of a protein-bound octanoyl chain to produce the
lipoyl cofactor. To activate its substrate for sulfur insertion, LipA uses a [4Fe
4S] cluster and S-adenosylmethionine (AdoMet) radical chemistry; the remainder of
the reaction mechanism, especially the source of the sulfur, has been less clear.
One controversial proposal involves the removal of sulfur from a second
(auxiliary) [4Fe-4S] cluster on the enzyme, resulting in destruction of the
cluster during each round of catalysis. Here, we present two high-resolution
crystal structures of LipA from Mycobacterium tuberculosis: one in its resting
state and one at an intermediate state during turnover. In the resting state, an
auxiliary [4Fe-4S] cluster has an unusual serine ligation to one of the irons.
After reaction with an octanoyllysine-containing 8-mer peptide substrate and 1 eq
AdoMet, conditions that allow for the first sulfur insertion but not the second
insertion, the serine ligand dissociates from the cluster, the iron ion is lost,
and a sulfur atom that is still part of the cluster becomes covalently attached
to C6 of the octanoyl substrate. This intermediate structure provides a clear
picture of iron-sulfur cluster destruction in action, supporting the role of the
auxiliary cluster as the sulfur source in the LipA reaction and describing a
radical strategy for sulfur incorporation into completely unactivated substrates.
PMID- 27506793
TI - Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis.
AB - Ferroptosis is form of regulated nonapoptotic cell death that is involved in
diverse disease contexts. Small molecules that inhibit glutathione peroxidase 4
(GPX4), a phospholipid peroxidase, cause lethal accumulation of lipid peroxides
and induce ferroptotic cell death. Although ferroptosis has been suggested to
involve accumulation of reactive oxygen species (ROS) in lipid environments, the
mediators and substrates of ROS generation and the pharmacological mechanism of
GPX4 inhibition that generates ROS in lipid environments are unknown. We report
here the mechanism of lipid peroxidation during ferroptosis, which involves
phosphorylase kinase G2 (PHKG2) regulation of iron availability to lipoxygenase
enzymes, which in turn drive ferroptosis through peroxidation of polyunsaturated
fatty acids (PUFAs) at the bis-allylic position; indeed, pretreating cells with
PUFAs containing the heavy hydrogen isotope deuterium at the site of peroxidation
(D-PUFA) prevented PUFA oxidation and blocked ferroptosis. We further found that
ferroptosis inducers inhibit GPX4 by covalently targeting the active site
selenocysteine, leading to accumulation of PUFA hydroperoxides. In summary, we
found that PUFA oxidation by lipoxygenases via a PHKG2-dependent iron pool is
necessary for ferroptosis and that the covalent inhibition of the catalytic
selenocysteine in Gpx4 prevents elimination of PUFA hydroperoxides; these
findings suggest new strategies for controlling ferroptosis in diverse contexts.
PMID- 27506794
TI - RNF122 suppresses antiviral type I interferon production by targeting RIG-I CARDs
to mediate RIG-I degradation.
AB - The activation of retinoic acid-inducible gene 1 (RIG-I), a cytoplasmic innate
sensor for viral RNA, is tightly regulated to maintain immune homeostasis
properly and prevent excessive inflammatory reactions other than initiation of
antiviral innate response to eliminate RNA virus effectively. Posttranslational
modifications, particularly ubiquitination, are crucial for regulation of RIG-I
activity. Increasing evidence suggests that E3 ligases play important roles in
various cellular processes, including cell proliferation and antiviral innate
signaling. Here we identify that E3 ubiquitin ligase RING finger protein 122
(RNF122) directly interacts with mouse RIG-I through MS screening of RIG-I
interacting proteins in RNA virus-infected cells. The transmembrane domain of
RNF122 associates with the caspase activation and recruitment domains (CARDs) of
RIG-I; this interaction effectively triggers RING finger domain of RNF122 to
deliver the Lys-48-linked ubiquitin to the Lys115 and Lys146 residues of RIG-I
CARDs and promotes RIG-I degradation, resulting in a marked inhibition of RIG-I
downstream signaling. RNF122 is widely expressed in various immune cells, with
preferential expression in macrophages. Deficiency of RNF122 selectively
increases RIG-I-triggered production of type I IFNs and proinflammatory cytokines
in macrophages. RNF122-deficient mice exhibit more resistance against lethal RNA
virus infection, with increased production of type I IFNs. Thus, we demonstrate
that RNF122 acts as a selective negative regulator of RIG-I-triggered antiviral
innate response by targeting CARDs of RIG-I and mediating proteasomal degradation
of RIG-I. Our study outlines a way for E3 ligase to regulate innate sensor RIG-I
for the control of antiviral innate immunity.
PMID- 27506795
TI - Assembly scaffold NifEN: A structural and functional homolog of the nitrogenase
catalytic component.
AB - NifEN is a biosynthetic scaffold for the cofactor of Mo-nitrogenase (designated
the M-cluster). Previous studies have revealed the sequence and structural
homology between NifEN and NifDK, the catalytic component of nitrogenase.
However, direct proof for the functional homology between the two proteins has
remained elusive. Here we show that, upon maturation of a cofactor precursor
(designated the L-cluster) on NifEN, the cluster species extracted from NifEN is
spectroscopically equivalent and functionally interchangeable with the native M
cluster extracted from NifDK. Both extracted clusters display nearly
indistinguishable EPR features, X-ray absorption spectroscopy/extended X-ray
absorption fine structure (XAS/EXAFS) spectra and reconstitution activities,
firmly establishing the M-cluster-bound NifEN (designated NifEN(M)) as the only
protein other than NifDK to house the unique nitrogenase cofactor. Iron chelation
experiments demonstrate a relocation of the cluster from the surface to its
binding site within NifEN(M) upon maturation, which parallels the insertion of M
cluster into an analogous binding site in NifDK, whereas metal analyses suggest
an asymmetric conformation of NifEN(M) with an M-cluster in one alphabeta-half
and an empty cluster-binding site in the other alphabeta-half, which led to the
proposal of a stepwise assembly mechanism of the M-cluster in the two alphabeta
dimers of NifEN. Perhaps most importantly, NifEN(M) displays comparable ATP
independent substrate-reducing profiles to those of NifDK, which establishes the
M-cluster-bound alphabeta-dimer of NifEN(M) as a structural and functional mimic
of one catalytic alphabeta-half of NifDK while suggesting the potential of this
protein as a useful tool for further investigations of the mechanistic details of
nitrogenase.
PMID- 27506796
TI - Oxidation and cyclization of casbene in the biosynthesis of Euphorbia factors
from mature seeds of Euphorbia lathyris L.
AB - The seed oil of Euphorbia lathyris L. contains a series of macrocyclic
diterpenoids known as Euphorbia factors. They are the current industrial source
of ingenol mebutate, which is approved for the treatment of actinic keratosis, a
precancerous skin condition. Here, we report an alcohol dehydrogenase-mediated
cyclization step in the biosynthetic pathway of Euphorbia factors, illustrating
the origin of the intramolecular carbon-carbon bonds present in lathyrane and
ingenane diterpenoids. This unconventional cyclization describes the ring closure
of the macrocyclic diterpene casbene. Through transcriptomic analysis of E.
lathyris L. mature seeds and in planta functional characterization, we identified
three enzymes involved in the cyclization route from casbene to jolkinol C, a
lathyrane diterpene. These enzymes include two cytochromes P450 from the CYP71
clan and an alcohol dehydrogenase (ADH). CYP71D445 and CYP726A27 catalyze regio
specific 9-oxidation and 5-oxidation of casbene, respectively. When coupled with
these P450-catalyzed monooxygenations, E. lathyris ADH1 catalyzes dehydrogenation
of the hydroxyl groups, leading to the subsequent rearrangement and cyclization.
The discovery of this nonconventional cyclization may provide the key link to
complete elucidation of the biosynthetic pathways of ingenol mebutate and other
bioactive macrocyclic diterpenoids.
PMID- 27506797
TI - Acinetobacter baumannii phenylacetic acid metabolism influences infection outcome
through a direct effect on neutrophil chemotaxis.
AB - Innate cellular immune responses are a critical first-line defense against
invading bacterial pathogens. Leukocyte migration from the bloodstream to a site
of infection is mediated by chemotactic factors that are often host-derived. More
recently, there has been a greater appreciation of the importance of bacterial
factors driving neutrophil movement during infection. Here, we describe the
development of a zebrafish infection model to study Acinetobacter baumannii
pathogenesis. By using isogenic A. baumannii mutants lacking expression of
virulence effector proteins, we demonstrated that bacterial drivers of disease
severity are conserved between zebrafish and mammals. By using transgenic
zebrafish with fluorescent phagocytes, we showed that a mutation of an
established A. baumannii global virulence regulator led to marked changes in
neutrophil behavior involving rapid neutrophil influx to a localized site of
infection, followed by prolonged neutrophil dwelling. This neutrophilic response
augmented bacterial clearance and was secondary to an impaired A. baumannii
phenylacetic acid catabolism pathway, which led to accumulation of phenylacetate.
Purified phenylacetate was confirmed to be a neutrophil chemoattractant. These
data identify a previously unknown mechanism of bacterial-guided neutrophil
chemotaxis in vivo, providing insight into the role of bacterial metabolism in
host innate immune evasion. Furthermore, the work provides a potentially new
therapeutic paradigm of targeting a bacterial metabolic pathway to augment host
innate immune responses and attenuate disease.
PMID- 27506798
TI - Circadian clock regulation of mRNA translation through eukaryotic elongation
factor eEF-2.
AB - The circadian clock has a profound effect on gene regulation, controlling
rhythmic transcript accumulation for up to half of expressed genes in eukaryotes.
Evidence also exists for clock control of mRNA translation, but the extent and
mechanisms for this regulation are not known. In Neurospora crassa, the circadian
clock generates daily rhythms in the activation of conserved mitogen-activated
protein kinase (MAPK) pathways when cells are grown in constant conditions,
including rhythmic activation of the well-characterized p38 osmosensing (OS) MAPK
pathway. Rhythmic phosphorylation of the MAPK OS-2 (P-OS-2) leads to temporal
control of downstream targets of OS-2. We show that osmotic stress in N. crassa
induced the phosphorylation of a eukaryotic elongation factor-2 (eEF-2) kinase,
radiation sensitivity complementing kinase-2 (RCK-2), and that RCK-2 is necessary
for high-level phosphorylation of eEF-2, a key regulator of translation
elongation. The levels of phosphorylated RCK-2 and phosphorylated eEF-2 cycle in
abundance in wild-type cells but not in cells deleted for OS-2 or the core clock
component FREQUENCY (FRQ). Translation extracts from cells grown in constant
conditions show decreased translational activity in the late subjective morning,
coincident with the peak in eEF-2 phosphorylation, and rhythmic translation of
glutathione S-transferase (GST-3) from constitutive mRNA levels in vivo is
dependent on circadian regulation of eEF-2 activity. In contrast, rhythms in
phosphorylated eEF-2 levels are not necessary for rhythms in accumulation of the
clock protein FRQ, indicating that clock control of eEF-2 activity promotes
rhythmic translation of specific mRNAs.
PMID- 27506799
TI - Lyme disease and relapsing fever Borrelia elongate through zones of peptidoglycan
synthesis that mark division sites of daughter cells.
AB - Agents that cause Lyme disease, relapsing fever, leptospirosis, and syphilis
belong to the phylum Spirochaetae-a unique lineage of bacteria most known for
their long, spiral morphology. Despite the relevance to human health, little is
known about the most fundamental aspects of spirochete growth. Here, using
quantitative microscopy to track peptidoglycan cell-wall synthesis, we found that
the Lyme disease spirochete Borrelia burgdorferi displays a complex pattern of
growth. B. burgdorferi elongates from discrete zones that are both spatially and
temporally regulated. In addition, some peptidoglycan incorporation occurs along
the cell body, with the notable exception of a large region at the poles. Newborn
cells inherit a highly active zone of peptidoglycan synthesis at midcell that
contributes to elongation for most of the cell cycle. Concomitant with the
initiation of nucleoid separation and cell constriction, second and third zones
of elongation are established at the 1/4 and 3/4 cellular positions, marking
future sites of division for the subsequent generation. Positioning of elongation
zones along the cell is robust to cell length variations and is relatively
precise over long distances (>30 um), suggesting that cells "sense" relative, as
opposed to absolute, cell length to establish zones of peptidoglycan synthesis.
The transition from one to three zones of peptidoglycan growth during the cell
cycle is also observed in relapsing fever Borrelia. However, this mode of growth
does not extend to representative species from other spirochetal genera,
suggesting that this distinctive growth mode represents an evolutionary divide in
the spirochete phylum.
PMID- 27506801
TI - Endocrine disorders in women with complex regional pain syndrome type I.
AB - BACKGROUND: The question of hormonal dysregulation in patients with CRPS I in
whole was investigated very scantily. There are only a few studies concerning
catecholamines, oestrogens and endorphins independently. Other hormones were
studied in patients with different other chronic pain conditions. Considering the
accumulation of sufficient knowledge about the role of disadaptation processes in
CRPS I pathogenesis and the role of the hypothalamic-pituitary-adrenal and
hypothalamic-pituitary-ovarian systems in the process of adaptation it was
logical and consistent to define the role of hormonal dysregulation of these
systems in patients with CRPS I. OBJECTIVES: Our objective was to determine the
role of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-ovarian systems
in pathogenesis of complex regional pain syndrome type I (CRPS I) in women.
METHODS: We investigated the pituitary gonadotropic function and the function of
sex glands in women with CRPS I and healthy volunteers by measuring the plasma
levels of estradiol (E2 ), follicle-stimulating hormone, luteinizing hormone,
prolactin, adrenocorticotropic hormone, and cortisol, and urinary excretion of 17
ketosteroids, 17-oxycocorticosteroids, epinephrine and norepinephrine. RESULTS:
Women with CRPS I were characterized by the decreased content of oestrogens in
the blood plasma and increased pituitary gonadotrophic function. The disturbed
ratio of anabolic and catabolic steroids in women with CRPS I was detected due to
lower adrenal cortex function. CONCLUSIONS: In patients with CRPS I endocrine
status is characterized by hormonal imbalances of the hypothalamic-pituitary
adrenal and hypothalamic-pituitary-gonadal systems. The changes in reproductive
and adaptation homeostasis characterize CRPS I as a form of the disease of
disadaptation. SIGNIFICANCE: This study determined the role of hypothalamic
pituitary-adrenal and hypothalamic-pituitary-ovarian systems in pathogenesis of
CRPS I.
PMID- 27506800
TI - Midgut microbiota and host immunocompetence underlie Bacillus thuringiensis
killing mechanism.
AB - Bacillus thuringiensis is a widely used bacterial entomopathogen producing
insecticidal toxins, some of which are expressed in insect-resistant transgenic
crops. Surprisingly, the killing mechanism of B. thuringiensis remains
controversial. In particular, the importance of the septicemia induced by the
host midgut microbiota is still debated as a result of the lack of experimental
evidence obtained without drastic manipulation of the midgut and its content.
Here this key issue is addressed by RNAi-mediated silencing of an immune gene in
a lepidopteran host Spodoptera littoralis, leaving the midgut microbiota
unaltered. The resulting cellular immunosuppression was characterized by a
reduced nodulation response, which was associated with a significant enhancement
of host larvae mortality triggered by B. thuringiensis and a Cry toxin. This was
determined by an uncontrolled proliferation of midgut bacteria, after entering
the body cavity through toxin-induced epithelial lesions. Consequently, the
hemolymphatic microbiota dramatically changed upon treatment with Cry1Ca toxin,
showing a remarkable predominance of Serratia and Clostridium species, which
switched from asymptomatic gut symbionts to hemocoelic pathogens. These
experimental results demonstrate the important contribution of host enteric flora
in B. thuringiensis-killing activity and provide a sound foundation for
developing new insect control strategies aimed at enhancing the impact of
biocontrol agents by reducing the immunocompetence of the host.
PMID- 27506802
TI - Psychometric Testing of the Chinese-Version Glover-Nilsson Smoking Behavioral
Questionnaire (GN-SBQ-C) for the Identification of Nicotine Dependence in Adult
Smokers in Taiwan.
AB - PURPOSE: The purposes of this study were to evaluate the psychometric properties,
reliability, and validity of the Chinese-version Glover-Nilsson Smoking
Behavioral Questionnaire (GN-SBQ-C) and assess the behavioral nicotine dependence
among community-dwelling adult smokers in Taiwan. METHOD: The methods used were
survey design, administration, and validation. A total of 202 adult smokers
completed a survey to assess behavioral dependence, nicotine dependence,
depression, social support, and demographic and smoking characteristics. Data
analysis included descriptive statistics, internal consistency reliability, t
test, exploratory factor analysis, independent t test, and Pearson product moment
correlation. RESULTS: The results showed that (1) the GN-SBQ-C has good internal
consistency reliability and stability (2-week test-retest reliability); (2) the
extracted one factor explained 41.80 % of the variance, indicating construct
validity; (3) the scale has acceptable concurrent validity, with significant
positive correlation between the GN-SBQ-C and nicotine dependence, depression,
and time smoking and negative correlation between the GN-SBQ-C and age and
exercise habit; and (4) the instrument has discriminant validity, supported by
significant differences between those with high and low-to-moderate nicotine
dependence, smokers greater than 43 years old and those 43 years old and younger,
and those who smoked 10 years or less and those smoking more than 10 years.
CONCLUSION: The 11-item GN-SBQ-C has satisfactory psychometric properties when
applied in a sample of Taiwanese adult smokers. The scale is feasible and valid
to use to assess smoking behavioral dependence.
PMID- 27506803
TI - Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for the Treatment of Obesity in
the ReCharge Trial.
AB - BACKGROUND: The ReCharge Trial demonstrated that a vagal blocking device (vBloc)
is a safe and effective treatment for moderate to severe obesity. This report
summarizes 24-month outcomes. METHODS: Participants with body mass index (BMI) 40
to 45 kg/m2, or 35 to 40 kg/m2 with at least one comorbid condition were
randomized to either vBloc therapy or sham intervention for 12 months. After 12
months, participants randomized to vBloc continued open-label vBloc therapy and
are the focus of this report. Weight loss, adverse events, comorbid risk factors,
and quality of life (QOL) will be assessed for 5 years. RESULTS: At 24 months,
123 (76 %) vBloc participants remained in the trial. Participants who presented
at 24 months (n = 103) had a mean excess weight loss (EWL) of 21 % (8 % total
weight loss [TWL]); 58 % of participants had >=5 % TWL and 34 % had >=10 % TWL.
Among the subset of participants with abnormal preoperative values, significant
improvements were observed in mean LDL (-16 mg/dL) and HDL cholesterol (+4
mg/dL), triglycerides (-46 mg/dL), HbA1c (-0.3 %), and systolic (-11 mmHg) and
diastolic blood pressures (-10 mmHg). QOL measures were significantly improved.
Heartburn/dyspepsia and implant site pain were the most frequently reported
adverse events. The primary related serious adverse event rate was 4.3 %.
CONCLUSIONS: vBloc therapy continues to result in medically meaningful weight
loss with a favorable safety profile through 2 years. TRIAL REGISTRATION:
https://clinicaltrials.gov/ct2/show/NCT01327976.
PMID- 27506804
TI - Cost-comparativeness of proton versus photon therapy.
AB - Proton beam radiotherapy (PBT) offers great promise in the treatment of a wide
variety of cancers owing to the sharp drop-off in radiation dose at a defined
point, known as the Bragg peak, beyond which there is no appreciable dose.
However, it is also well-understood that PBT is associated with large economic
costs, including both capital investment and operating costs. From a medical as
well as societal perspective, therefore, it is important to be aware of the
economic implications of new technologies such as PBT, and to evaluate the cost
effectiveness based on different clinical and treatment scenarios. This review
examines PBT from a health economics perspective, evaluating both the design and
results of costeffectiveness (CE) studies that have been performed previously. We
further examine several salient variables that can affect CE of PBT, including
patient, tumor, treatment, and logistical factors. We discuss the implication of
technological advances on PBT delivery, and its impact on overall healthcare
delivery costs. Additionally, we evaluate the status of economic analyses for PBT
and discuss the role of ongoing and future CE studies in better defining the
economic role of PBT as part of modern cancer therapy.
PMID- 27506805
TI - Treatment of common pediatric CNS malignancies with proton therapy.
AB - Radiation therapy plays an important role in the management of pediatric CNS
malignancies. With the improving outcomes of these patients, the potential risk
of late toxicities present with current radiation therapy techniques (i.e., 3D
CRT, IMRT, VMAT) has become apparent. Proton therapy (PRT), due to its unique
physical characteristics, provides an advantage in reducing unintended dose to
normal tissue structures, and the resultant acute and late side effects of this
dose "bath". In this review we will highlight the current standards of care, and
the benefits achieved with using PRT in treating common childhood CNS tumors.
PMID- 27506806
TI - Molecular features of response to anti-PD-1 therapy.
PMID- 27506807
TI - Chromodomain-helicase-DNA-binding protein 4: a novel therapeutic target in liver
cancer stem cells.
PMID- 27506808
TI - Reduced acute toxicity and improved efficacy from intensity-modulated proton
therapy (IMPT) for the management of head and neck cancer.
AB - Cancers in the head and neck area are usually close to several critical organ
structures. Traditional external-beam photon radiation therapy unavoidably
exposes these structures to significant doses of radiation, which can lead to
serious acute and chronic toxicity. Intensity-modulated proton therapy (IMPT),
however, has dosimetric advantages that allow it to deposit high doses within the
target while largely sparing surrounding structures. Because of this advantage,
IMPT has the potential to improve both tumor control and toxicity. To determine
the degree to which IMPT can reduce toxicity and improve tumor control, more
randomized trials are needed that directly compare IMPT with intensity-modulated
photon therapy. Here we examine the existing evidence on the efficacy and
toxicity of IMPT for treating cancers at several anatomic subsites of the head
and neck. We also report on the ability of IMPT to reduce malnutrition, and
gastrostomy tube dependence and improve patient-reported outcomes (PROs).
PMID- 27506809
TI - Arthroscopic treatment of global pincer-type femoroacetabular impingement.
AB - PURPOSE: Few studies have evaluated the role of hip arthroscopy in patients with
coxa profunda. The purposes of this study are to (1) report functional hip
outcomes after arthroscopic treatment of patients with femoroacetabular
impingement (FAI) associated with radiographic coxa profunda and (2) evaluate
factors associated with poor hip function at minimum 2 years following surgery in
this specific cohort. METHODS: This retrospective review included patients with
radiographic sign of coxa profunda who underwent hip arthroscopy to treat FAI.
Preoperative and post-operative radiographs were reviewed to determine changes in
lateral centre-edge angle (CEA), the presence and correction of Cam deformity,
and Tonnis grade of osteoarthritis. Hip functional scores, including modified
Harris Hip Score, Hip Outcome Score, and IHOT score, were obtained at a minimum
of 2 years following surgery. RESULTS: The study cohort included 46 patients with
a mean preoperative CEA of 39.9 (+/-2.4) degrees which decreased to a mean of
30.8 (+/-1.8) degrees post-operatively. At a mean follow-up of 2.5 years (+/
0.5), the mean mHHS and IHOT scores were 79.5 (+/-20.2) and of 69.7 (+/-28.3),
respectively. Increased preoperative (p = 0.02) and post-operative (p = 0.001)
Tonnis Osteoarthritis Grade was associated with a lower mHHS. CONCLUSIONS:
Patients with coxa profunda can achieve similar functional scores to more
traditional FAI cohorts after arthroscopic treatment. Baseline osteoarthritis is
predictive of lower hip function after hip arthroscopy. This study demonstrates
that patients with global over-coverage can benefit from hip arthroscopy and may
influence surgeons to treat these patients with less invasive arthroscopic
techniques which avoid the morbidity of open surgical procedures. LEVEL OF
EVIDENCE: Retrospective case series, Level IV.
PMID- 27506810
TI - Remaining mild varus limb alignment leads to better clinical outcome in total
knee arthroplasty for varus osteoarthritis.
AB - PURPOSE: Postoperative neutral limb alignment [femorotibial mechanical axis
(FTMA) 180 degrees +/- 3 degrees ] is generally considered to be one of the
prerequisites for successful total knee arthroplasty (TKA). However, the
influence of residual malalignment on clinical and functional outcomes after TKA
is unknown. Therefore, the purpose of this study was to investigate the
relationship between postoperative limb alignment and clinical outcomes in Asian
patients who underwent primary TKA. METHODS: The study included 220 knees with a
mean age of 73.5 years who underwent primary TKA for varus-type osteoarthritis;
the mean follow-up period was 3.6 years. Patients were divided into four groups
based on postoperative FTMA: severe varus (FTMA < 174 degrees , n = 15), mild
varus (FTMA >177 degrees and <=174 degrees , n = 61), neutral (FTMA 180 degrees
+/- 3 degrees , n = 128), and valgus (FTMA > 183 degrees , n = 16). Knee Society
Knee Score (KSKS) and Knee Society Functional Score (KSFS) were compared among
the 4 groups. RESULTS: KSKS and KSFS showed significant improvement in all
groups. There were no statistically significant differences for postoperative
KSKS among the four groups. For KSFS, however, the severe varus and valgus groups
exhibited significantly lower values compared with the mild varus and neutral
groups. CONCLUSION: Postoperative mild varus alignment as well as neutral
mechanical alignment of the lower limb led to excellent functional outcomes. For
the clinical relevance, postoperative mild varus alignment of the lower limb is
acceptable following TKA for varus-type osteoarthritis. LEVEL OF EVIDENCE: IV.
PMID- 27506811
TI - Optimizing the process of fertility preservation in pediatric female cancer
patients - a multidisciplinary program.
AB - BACKGROUND: Current evidence indicates sub-optimal incidence of fertility
preservation (FP) in eligible patients. We present herein our designated
multidisciplinary program for FP in pediatric and adolescent population and
present our data on FP in female patients. METHODS: Pediatric patients (age 0-18)
who were candidate for highly gonadotoxic treatments were referred to FP program
for a multidisciplinary discussion and gonadal risk-assessment followed by either
oocyte cryopreservation or ovarian cryopreservation (OCP) for female patients,
and sperm banking for male patients. The OCP protocol consists of aspiration of
oocytes from small antral follicles and in-vitro maturation followed by
cryopreservation, as well as ovarian tissue cryopreservation. RESULTS: The
establishment of a designated FP program resulted in a significant increase in
referral and subsequent FP procedures of all eligible patients. Sixty-two female
patients were referred for FP discussion during a period of 36 months; 41
underwent OCP; 11 underwent oocyte cryopreservation and six were declined due to
parental decision. The median age was 13.2y (range 18 months-18y). Thirty-two
(51.6 %) were chemotherapy-naive. Seventeen patients (27 %) had sarcoma, 16
patients (26 %) had acute leukemia. The mean number of mature oocytes that were
eventually vitrified was significantly higher in chemotherapy-naive patients
compared with chemotherapy-exposed patients (mean 12 oocytes (1-42) versus 2 (0
7)). CONCLUSION: Multidisciplinary programs that encompass experts of all
relevant fields, skilled laboratory resources and a facilitated path appear to
maximize the yield. We observed a considerable higher referral rates following
launching a designated program and earlier OCP in chemo-naive patients that
culminated in a better fertility preservation procedure.
PMID- 27506812
TI - Antibiotic dosing in obesity: a BIG challenge.
PMID- 27506813
TI - Morphine enhances IL-1beta release through toll-like receptor 4-mediated
endocytic pathway in microglia.
AB - Morphine creates a neuroinflammatory response and enhances release of the
proinflammatory cytokines like interleukin-1beta (IL-1beta), which compromises
morphine analgesia as well as induces morphine tolerance. In this study, we
attempted to investigate the mechanisms of morphine induced IL-1beta synthesis
and release. Microglial cells were treated with morphine (100 MUM) once daily for
3 days. Control groups underwent the same procedure but received sterile saline
injection instead of morphine. Toll-like receptor 4 (TLR4) and P2X4 receptor
(P2X4R) signaling were analyzed using Western blot; immunofluorescence was used
to detect the signaling of CD68; real-time RT-PCR and ELISA kit was used to
measure the messenger RNA and protein synthesis and release level of IL-1beta.
Morphine enhanced IL-1beta synthesis and P2X4R protein expression. TLR4 were
responsible for morphine-induced IL-1beta synthesis, while morphine-induced IL
1beta release was via P2X4R. Morphine-induced IL-1beta release is mediated by
endocytosis of TLR4. These results indicated that TLR4 and P2X4R pathways
mediated IL-1beta synthesis and release in microglia followed chronic morphine.
TLR4 internalization is the main mechanism of morphine-induced microglia
activation and IL-1beta release.
PMID- 27506814
TI - Computed tomography in the investigation and management of obturator hernia.
AB - INTRODUCTION: Obturator hernias are a rare groin hernia. They are most commonly
found incidentally during laparoscopic inguinal hernia repair. We investigated
our experience with obturator hernias in the elective and emergency setting.
METHODS: Cases of obturator hernia were identified from a hospital database and
reviewed retrospectively over the last 10 years. There were no exclusions. There
were a number of surgeons involved with an interest in groin hernia surgery.
RESULTS: Twenty-one patients were included. The mean age was 66 years old. Eleven
were male. There were four emergency presentations. One emergency case presented
with small bowel obstruction, while the other three cases presented with groin
pain. Two patients had a preoperative computed tomography, which showed an
obturator hernia confirmed at surgery. The patient with small bowel obstruction
had an open bowel resection alone with no hernia repair. They were discharged
with no complications or recurrence on follow-up. The other three cases had a
mesh repair (one laparoscopic, one laparotomy, one pre-peritoneal). One patient
who underwent a laparotomy died of a post-operative pneumonia. The others were
discharged uneventfully. In the elective group of 17 patients, 8 patients were
taken for an elective laparoscopic inguinal hernia repair but found to actually
have an obturator hernia alone. An obturator hernia was found incidentally with
an inguinal hernia in three patients. Five patients were expected to have an
obturator hernia on clinical examination alone. At surgery, an obturator hernia
was found in three cases. In the other two cases, no hernia was found. One
patient had a pre-operative computed tomography, which showed an obturator hernia
confirmed at surgery. CONCLUSIONS: Computed tomography would be recommended in
cases of diagnostic uncertainty. It may avoid unnecessary surgery in the elective
setting and allow a focused procedure in the emergency setting. Laparoscopic
repair is feasible in the emergency and elective setting with excellent results.
PMID- 27506815
TI - Effective treatment of spasticity using dronabinol in pediatric palliative care.
AB - BACKGROUND: Cannabis extracts have a wide therapeutic potential but in many
countries they have not been approved for treatment in children so far.
OBJECTIVE: We conducted an open, uncontrolled, retrospective study on the
administration of dronabinol to determine the value, efficacy, and safety of
cannabis-based medicines in the treatment of refractory spasticity in pediatric
palliative care. DESIGN AND PARTICIPANTS: Sixteen children, adolescents and young
adults having complex neurological conditions with spasticity (aged 1.3-26.6
years, median 12.7 years) were treated with dronabinol by our specialized
pediatric palliative care team between 01.12.2010 and 30.04.2015 in a home-care
setting. Therapeutic efficacy and side effects were closely monitored. RESULTS:
Drops of the 2.5% oily tetrahydrocannabinol solution (dronabinol) were
administered. A promising therapeutic effect was seen, mostly due to abolishment
or marked improvement of severe, treatment resistant spasticity (n = 12). In two
cases the effect could not be determined, two patients did not benefit. The
median duration of treatment was 181 days (range 23-1429 days). Dosages to obtain
a therapeutic effect varied from 0.08 to 1.0 mg/kg/d with a median of 0.33
mg/kg/d in patients with a documented therapeutic effect. When administered as an
escalating dosage scheme, side effects were rare and only consisted in vomiting
and restlessness (one patient each). No serious and enduring side effects
occurred even in young children and/or over a longer period of time. CONCLUSIONS:
In the majority of pediatric palliative patients the treatment with dronabinol
showed promising effects in treatment resistant spasticity.
PMID- 27506816
TI - Is genotyping of single isolates sufficient for population structure analysis of
Pseudomonas aeruginosa in cystic fibrosis airways?
AB - BACKGROUND: The primary cause of morbidity and mortality in cystic fibrosis (CF)
patients is lung infection by Pseudomonas aeruginosa. Therefore much work has
been done to understand the adaptation and evolution of P. aeruginosa in the CF
lung. However, many of these studies have focused on longitudinally collected
single isolates, and only few have included cross-sectional analyses of entire P.
aeruginosa populations in sputum samples. To date only few studies have used the
approach of metagenomic analysis for the purpose of investigating P. aeruginosa
populations in CF airways. RESULTS: We analysed five metagenomes together with
longitudinally collected single isolates from four recently chronically infected
CF patients. With this approach we were able to link the clone type and the
majority of SNP profiles of the single isolates to that of the metagenome(s) for
each individual patient. CONCLUSION: Based on our analysis we find that when
having access to comprehensive collections of longitudinal single isolates it is
possible to rediscover the genotypes of the single isolates in the metagenomic
samples. This suggests that information gained from genome sequencing of
comprehensive collections of single isolates is satisfactory for many
investigations of adaptation and evolution of P. aeruginosa to the CF airways.
PMID- 27506818
TI - Slobodan Lang.
PMID- 27506817
TI - Social Network Influence on HIV Testing Among Urban Men in Tanzania.
AB - Men in sub-Saharan Africa have low HIV testing rates. Social networks exert an
important influence on men's HIV-related behavior. We examined associations
between network factors and HIV testing among men in Dar es Salaam, Tanzania.
Data are from the baseline assessment of an HIV prevention trial with 48
primarily male networks. Among 923 sexually active men, 52 % had ever tested for
HIV. In a random effects logistic regression model, men in the network core were
1.50 times more likely (p < .05) to test than those in the periphery. Percentage
of women in the network was associated with men's increased HIV testing (AOR
4.24, p < .05). Perception of network HIV stigma was negatively associated with
HIV testing (AOR 0.92, p < .01). Thinking at least one close friend tested for
HIV was associated with increased testing (AOR 2.66, p < .001). Social network
interventions are a promising approach for scaling up men's HIV testing.
PMID- 27506820
TI - Incidence, Treatment Intensity, and Incremental Annual Expenditures for Patients
Experiencing a Cardiac Implantable Electronic Device Infection: Evidence From a
Large US Payer Database 1-Year Post Implantation.
AB - BACKGROUND: Because of the increasing use of cardiac implantable electronic
devices (CIEDs), it is important to estimate the incidence and annual healthcare
expenditures associated with CIED infections. METHODS AND RESULTS: Patients with
a record of an initial or replacement (full implant or generator only) CIED
implant during the calendar years 2009 to 2012 in MarketScan Commercial Claims
and Medicare Supplemental database were identified. CIED infections were
classified into 4 categories: (1) infection not managed by inpatient admission
nor implant removal, (2) infection managed by inpatient admission but no implant
removal, (3) infection managed by an implant removal either in an inpatient or in
an outpatient setting, and (4) infection with severe sepsis and managed in an
inpatient setting with implant removal. Using separate models for initial and
replacement cohorts, annualized incidence of infection and incremental annual
expenditures by treatment intensity were estimated. Cumulative incidence of
infection at 1 year post implant was 1.18% for initial CIED implants and 2.37%
for replacement. Median time to infection was 35 days for initial and 23 days for
replacement. Incremental healthcare expenditures by treatment intensity
categories for initial implant patients at 1 year were $16 651, $104 077, $45
291, and $279 744. For replacement patients, incremental expenditures at 1 year
by treatment intensity categories were $26 857, $43 541, $48 759, and $362 606.
CONCLUSIONS: The management of CIED infections results in a substantial
healthcare burden with a significant increase in annual expenditures the year
after implant when device infection occurs.
PMID- 27506819
TI - Association between perceived neighbourhood characteristics, physical activity
and diet quality: results of the Brazilian Longitudinal Study of Adult Health
(ELSA-Brasil).
AB - BACKGROUND: The study explores associations between perceived neighbourhood
characteristics, physical activity and diet quality, which in Latin America and
Brazil have been scarcely studied and with inconsistent results. METHODS: We
conducted a cross-sectional analysis of 14,749 individuals who participated in
the Brazilian Longitudinal Study of Adult Health (Estudo Longitudinal de Saude do
Adulto, ELSA-Brasil) baseline. The study included current and retired civil
servants, aged between 35 and 74 years, from universities and research institutes
in six Brazilian states. The International Physical Activity Questionnaire (IPAQ)
long form was used to characterize physical activity during leisure time and
commuting; additional questions assessed how often fruit and vegetables were
consumed, as a proxy for diet quality. Neighbourhood characteristics were
evaluated by the "Walking Environment" and "Availability of Healthy Foods" scales
originally used in the Multi-Ethnic Study of Atherosclerosis (MESA). Associations
were examined using multinomial logistic regression. RESULTS: Perceiving a more
walkable neighbourhood was positively associated with engaging in leisure time
physical activity and doing so for longer weekly. Compared with those who saw
their neighbourhood as less walkable, those who perceived it as more walkable had
1.69 (95 % CI 1.57-1.83) and 1.39 (1.28-1.52) greater odds of engaging in leisure
time physical activity for more than 150 min/week or up to 150 min/week (vs.
none), respectively. Perceiving a more walkable neighbourhood was also positively
associated with transport-related physical activity. The same pattern was
observed for diet: compared with participants who perceived healthy foods as less
available in their neighbourhood, those who saw them as more available had odds
1.48 greater (1.31-1.66) of eating fruits, and 1.47 greater (1.30-1.66) of eating
vegetables, more than once per day. CONCLUSIONS: Perceived walkability and
neighbourhood availability of healthy food were independently associated with the
practice of physical activity and diet quality, respectively, underlining the
importance of neighbourhood-level public policies to changing and maintaining
health-related habits.
PMID- 27506822
TI - Toward an absolute NMR shielding scale using the spin-rotation tensor within a
relativistic framework.
AB - One of the most influential articles showing the best way to get the absolute
values of NMR magnetic shieldings, sigma (non-measurables) from both accurate
measurements and theoretical calculations, was published a long time ago by
Flygare. His model was shown to break down when heavy atoms are involved. This
fact motivated the development of new theories of nuclear spin-rotation (SR)
tensors, which consider electronic relativistic effects. One was published
recently by some of us. In this article we take another step further and propose
three different models that generalize Flygare's model. All of them are written
using four-component relativistic expressions, though the two-component
relativistic SO-S term also appears in one. The first clues for these
developments were built from the relationship among sigma and the SR tensors
within the two-component relativistic LRESC model. Besides, we had to introduce a
few other well defined assumptions: (i) relativistic corrections must be included
in a way to best reproduce the relationship among the (e-e) term (called
"paramagnetic" within the non-relativistic domain) of sigma and its equivalent
part of the SR tensor, (ii) as happens in Flygare's rule, the shielding of free
atoms shall be included to improve accuracy. In the highest accurate model, a new
term known as Spin-orbit due to spin, SO-S (in this mechanism the spin-Zeeman
Hamiltonian replaces the orbital-Zeeman Hamiltonian), is included. We show the
results of the application of those models to halogen containing linear
molecules.
PMID- 27506821
TI - Multicenter Experience With Catheter Ablation for Ventricular Tachycardia in
Lamin A/C Cardiomyopathy.
AB - BACKGROUND: Lamin A/C (LMNA) cardiomyopathy is a genetic disease with a
proclivity for ventricular arrhythmias. We describe the multicenter experience
with percutaneous catheter ablation of sustained monomorphic ventricular
tachycardia (VT) in LMNA cardiomyopathy. METHODS AND RESULTS: Twenty-five
consecutive LMNA mutation patients from 4 centers were included (mean age, 55+/-9
years; ejection fraction, 34+/-12%; VT storm in 36%). Complete atrioventricular
block was present in 11 patients; 3 patients were on mechanical circulatory
support for severe heart failure. A median of 3 VTs were inducible per patient;
in 82%, mapping was consistent with origin from scar in the basal left ventricle,
particularly the septum, but also basal inferior wall and subaortic mitral
continuity. After multiple procedures (median 2/patient; transcoronary alcohol in
6 and surgical cryoablation in 2 patients), acute success (noninducibility of any
VT) was achieved in only 25% of patients. Partial success (inducibility of a
nonclinical VT only: 50%) and failure (persistent inducibility of clinical VT:
12.5%) was attributed to intramural septal substrate in 13 of 18 patients (72%).
Complications occurred in 25% of patients. After a median follow-up of 7 months
after the last procedure, 91% experienced >=1 VT recurrence, 44% received or were
awaiting mechanical circulatory support or transplant for end-stage heart
failure, and 26% died. CONCLUSIONS: Catheter ablation of VT associated with LMNA
cardiomyopathy is associated with poor outcomes including high rate of arrhythmia
recurrence, progression to end-stage heart failure, and high mortality. Basal
septal scar and intramural VT origin makes VT ablation challenging in this
population.
PMID- 27506823
TI - Reversed-phase separation parameters for intact proteins using liquid
chromatography with triple quadrupole mass spectrometry.
AB - The separation of intact proteins is inherently more complex than that of small
molecules using reversed-phase liquid chromatography. The goal of this work was
to determine a reasonable set of operational parameters (a recommended starting
point for other analysts) for the separation of intact proteins and their
detection by triple quadrupole mass spectrometry. Although protein separations
have been studied for many years, the direct detection of intact proteins with
mass spectrometry requires special considerations of mobile phase additives to
achieve efficient separation and sensitive detection. Myoglobin, cytochrome c,
lactalbumin, lysozyme, and ubiquitin were used as model analytes to investigate
chromatographic method development using a triple quadrupole mass spectrometer
and detection by multiple reaction monitoring. Chromatographic parameters
including the concentration of trifluoroacetic acid, flow rate, gradient slope,
temperature, mobile phase composition, and stationary phase chemistry were
evaluated. Protein charge state profiles were also monitored for temperature and
modifier effects. An optimized method using 0.2 mL/min flow rate, 15% gradient
slope, and 75 degrees C with a combined trifluoroacetic acid and formic acid
modified mobile phase was developed.
PMID- 27506824
TI - Litorisediminivivensgilvus gen. nov., sp. nov., isolated from a tidal flat.
AB - A Gram-stain-negative, non-flagellated, aerobic and coccoid, ovoid or rod-shaped
bacterium, designated YSM-17T, was isolated from tidal flat sediment collected
from the South Sea, South Korea, and subjected to a polyphasic taxonomic study.
The novel strain grew optimally at 30 degrees C, at pH 6.5-8.0 and in the
presence of 2.0-3.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene
sequences showed that strain YSM-17T forms a distinct evolutionary lineage
independent of other taxa in the family Rhodobacteraceae. Strain YSM-17T
exhibited 16S rRNA gene sequence similarity values of 96.8 and 96.6 % to the type
strains of Pseudopelagicola gijangensis and Pelagicola litoralis, respectively,
and of less than 96.5 % to the type strains of other recognized taxa. Strain YSM
17T contained Q-10 as the predominant ubiquinone and C18 : 1omega7c as the major
fatty acid. The major polar lipids detected in strain YSM-17T were
phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and one
unidentified aminolipid. The fatty acid and polar lipid profiles of strain YSM
17T were distinguished from those of the genera Pseudopelagicola and Pelagicola.
The DNA G+C content of strain YSM-17T was 64.6+/-0.04 mol%. On the basis of the
phylogenetic, chemotaxonomic and other phenotypic properties, strain YSM-17T is
considered to represent a novel species of a new genus within the family
Rhodobacteraceae, for which the name Litorisediminivivensgilvus gen. nov., sp.
nov., is proposed. The type strain of Litorisediminivivensgilvus is YSM-17T
(=KCTC 52249T=NBRC 112330T).
PMID- 27506825
TI - Age and sex differences in immune response following LPS treatment in mice.
AB - Puberty is an important developmental event that is marked by the reorganizing
and remodeling of the brain. Exposure to stress during this critical period of
development can have enduring effects on both reproductive and non-reproductive
behaviors. The purpose of this study was to investigate age and sex differences
in immune response by examining sickness behavior, body temperature changes, and
serum cytokine levels following an immune challenge. The effects of circulating
gonadal hormones on age and sex differences in immune response were also
examined. Results showed that male mice display more sickness behavior and
greater fluctuations in body temperature following LPS treatment than female
mice. Moreover, adult male mice display more sickness behavior and a greater drop
in body temperature following LPS treatment compared to pubertal male mice.
Following gonadectomy, pubertal and adult males displayed steeper and prolonged
drops in body temperature compared to sham-operated counterparts. Gonadectomy did
not eliminate sex differences in LPS-induced body temperature changes, suggesting
that additional factors contribute to the observed differences. LPS treatment
increased cytokine levels in all mice. However, the increase in pro-inflammatory
cytokines was higher in adult compared to pubertal mice, while the increase in
anti-inflammatory cytokines was greater in pubertal than in adult mice. Our
findings contribute to a better understanding of age and sex differences in acute
immune response following LPS treatment and possible mechanisms involved in the
enduring alterations in behavior and brain function following pubertal exposure
to LPS.
PMID- 27506826
TI - Erratum to: The short-term association of selected components of fine particulate
matter and mortality in the Denver Aerosol Sources and Health (DASH) study.
PMID- 27506827
TI - Intratumoural interleukin 12 gene therapy stimulates the immune system and
decreases angiogenesis in dogs with spontaneous cancer.
AB - Interleukin 12 (IL-12) is a powerful immunostimulatory cytokine with a strong
antitumoural activity. In this work, the immunological, anti-angiogenic and
clinical effects of three consecutive intratumoural IL-12 electrogene therapy
(EGT) treatments were evaluated in nine dogs with spontaneous cancer. In all the
dogs, tumour biopsies and blood samples were taken prior, during and after the
intratumoural IL-12 EGT (on days 1, 8, 35 and 1, 3, 8, 15, 35, respectively). An
initial decrease in immune cells was followed by an increase above baseline 1-3
weeks after treatment initiation. Interestingly, the decrease in peripheral
leukocytes 2 days after the first intratumoural IL-12 EGT coincided with erythema
and tumour swelling. Transient increases of IL-12 and interferon gamma were
measured in the serum and the tumour tissue, whereas IL-10 transiently increased
only in the serum. The effect of intratumoural IL-12 EGT on the levels of IL-24
and vascular endothelial growth factor in the sera and tumour biopsies differed
per dog. Via contrast-enhanced ultrasound (US) (on days 1, 8 and 35), we
demonstrated that intratumoural IL-12 EGT resulted in a significant decrease of
the relative blood volume and blood flow speed in the tumour compared with
baseline. Metastases were present in two dogs. In one of these dogs, IL-12 EGT of
the primary tumour caused a transient partial regression of the metastases, but
not of the primary tumour. The second dog with metastases did not survive long
enough to complete the entire treatment cycle. Despite encouraging
immunostimulatory and anti-angiogenic effects after intratumoural IL-12 EGT, no
clinically relevant outcomes were observed in this study, as persistent tumour
regression could not be obtained. On the other hand, the laboratory and US
results hold great promise for combinatorial strategies of intratumoural IL-12
EGT with conventional antitumour (immuno)therapies.
PMID- 27506828
TI - An unusual course of aortic arch through an accessory fissure of left upper lobe
of the lung: extramediastinal aortic arch.
AB - In this case report, we present an unexpected, extramediastinal course of aortic
arch through an accessory fissure of left upper lobe of the lung in a 19-year-old
healthy man.
PMID- 27506830
TI - Structure and Modification of Electrode Materials for Protein Electrochemistry.
AB - The interactions between proteins and electrode surfaces are of fundamental
importance in bioelectrochemistry, including photobioelectrochemistry. In order
to optimise the interaction between electrode and redox protein, either the
electrode or the protein can be engineered, with the former being the most
adopted approach. This tutorial review provides a basic description of the most
commonly used electrode materials in bioelectrochemistry and discusses approaches
to modify these surfaces. Carbon, gold and transparent electrodes (e.g. indium
tin oxide) are covered, while approaches to form meso- and macroporous structured
electrodes are also described. Electrode modifications include the chemical
modification with (self-assembled) monolayers and the use of conducting polymers
in which the protein is imbedded. The proteins themselves can either be in
solution, electrostatically adsorbed on the surface or covalently bound to the
electrode. Drawbacks and benefits of each material and its modifications are
discussed. Where examples exist of applications in photobioelectrochemistry,
these are highlighted.
PMID- 27506829
TI - Visualization of the olfactory nerve using constructive interference in steady
state magnetic resonance imaging.
AB - PURPOSE: The olfactory nerve (OlfN) is a small neural structure with inconsistent
visualization on neuroimages. The aim of this study was to delineate the
intracranial course of the OlfN using constructive interference in steady state
magnetic resonance (MR) imaging. METHODS: A total of 168 patients were enrolled
in this study. Following initial examinations with conventional MR sequences,
constructive interference in steady-state sequence (CISS) was performed in
coronal and axial sections. RESULTS: On coronal sections, the OlfN was entirely
visualized in 90 % of patients on the right and 92 % on the left, coursing along
the olfactory sulcus. Complete visualization of the OlfN occurred in 100 % of
patients on serial axial images. The OlfN was classified into four portions based
on the topographical differences and surrounding structures. The olfactory fossa
exhibited considerable variability at the midlevel of the olfactory bulb on
coronal images. Characteristic appearance of the OlfN with respect to age range
or gender was not observed. CONCLUSIONS: The OlfN follows a highly consistent
course along the olfactory sulcus. Thin-sliced, CISS sequences are useful for
consistent visualization of the OlfN.
PMID- 27506831
TI - In Vitro-In Vivo Carcinogenicity.
AB - The evaluation of the carcinogenic potential of chemicals constitutes an
essential step in assessing the risk that the chemicals pose to human health. The
"gold standard" method to evaluate the carcinogenic potential of chemicals is the
carcinogenicity test in laboratory animals. However, because carcinogenicity
studies in vivo are extremely time-consuming, expensive, make use of a high
number of animals, and cannot be used to screen a high number of compounds at the
same time, various different in vitro cell transformation assays have been
developed. In this report, procedures to test the carcinogenicity in vivo and in
vitro are described, whereby in the latter case three extensively evaluated test
systems (the BALB/c 3T3 cell transformation assay, the Bhas 42 cell
transformation assay, and the Syrian hamster embryo assay) are presented. Their
performance shows that they are a useful complement to in vitro genotoxicity test
batteries, can be used to identify non-genotoxic carcinogens, and as screening
assays may significantly limit the number of chemicals to undergo an in vivo
carcinogenicity testing, thereby strongly reducing the number of laboratory
animals to be used. In the future, the development of human cell line-based
transformation assays may contribute to increase further their relevance and the
willingness to incorporate them into existing in vitro toxicity test batteries.
PMID- 27506832
TI - Hazardous drinking among young adults seeking outpatient mental health services.
AB - BACKGROUND: Alcohol use can have a significant negative impact on young adults in
mental health treatment. This cross-sectional study examined prevalence and
factors associated with hazardous drinking among young adults seeking outpatient
mental health services, rate of alcohol use disorders (AUDs), and the
relationship between hazardous drinking and other types of substance use.
METHODS: Participants were 487 young adults ages 18-25 who completed self
administered computerized screening questions for alcohol and drug use. Alcohol
use patterns were assessed and predictors of hazardous drinking (>=5 drinks on
one or more occasions in the past year) were identified using logistic
regression. RESULTS: Of the 487 participants, 79.8 % endorsed prior-year alcohol
use, 52.3 % reported one or more episodes of hazardous drinking in the prior year
and 8.2 % were diagnosed with an AUD. Rates of recent and lifetime alcohol,
tobacco and marijuana use were significantly greater in those with prior-year
hazardous drinking. In logistic regression, prior-year hazardous drinking was
associated with lifetime marijuana use (OR 3.30, p < 0.001; 95 % CI 2.05, 5.28),
lifetime tobacco use (OR 1.88, p = 0.004; 95 % CI 1.22, 2.90) and older age (OR
1.18 per year, p < 0.001; 95 % CI 1.08, 1.29). CONCLUSIONS: In an outpatient
mental health setting, high rates of hazardous drinking were identified, and
drinking was associated with history of other substance use. Results highlight
patient characteristics associated with hazardous drinking that mental health
providers should be aware of in treating young adults, especially older age and
greater use of tobacco and marijuana.
PMID- 27506834
TI - Insights on stock structure of round sardinella Sardinella aurita off north-west
Africa based on otolith shape analysis.
AB - This study examines the geographic variability in otolith shape of round
sardinella Sardinella aurita as a tool for stock discrimination. Fish were
analysed from six sampling locations from Senegal to the Mediterranean coast of
Morocco. A combination of otolith shape indices and elliptic Fourier descriptors
was investigated by multivariate statistical procedures. Within the studied area,
three distinct groups were identified with an overall correct classification of
78%. Group A: Nador (Alboran Sea), group B: Casablanca (northern Morocco) and
group C: Senegalese-Mauritanian. The results of this study confirm the absence of
an Atlantic Ocean-Mediterranean Sea transition for this species, the Gibraltar
Strait acting as an efficient barrier for S. aurita population separation. Off
north-west Africa, fish from northern Morocco form a single group which is
clearly isolated from Senegalese-Mauritanian waters, confirming the existence of
a distinct stock in this area. Among group C, some discontinuity exists and
suggests the existence of a sedentary fraction of S. aurita in northern
Mauritania (Arguin Bank). The results are discussed in relation to oceanographic
features and physical barriers to dispersal and fish management strategy in the
study area.
PMID- 27506833
TI - Transcriptional analysis of the conidiation pattern shift of the entomopathogenic
fungus Metarhizium acridum in response to different nutrients.
AB - BACKGROUND: Most fungi, including entomopathogenic fungi, have two different
conidiation patterns, normal and microcycle conidiation, under different culture
conditions, eg, in media containing different nutrients. However, the mechanisms
underlying the conidiation pattern shift are poorly understood. RESULTS: In this
study, Metarhizium acridum undergoing microcycle conidiation on sucrose yeast
extract agar (SYA) medium shifted to normal conidiation when the medium was
supplemented with sucrose, nitrate, or phosphate. By linking changes in nutrients
with the conidiation pattern shift and transcriptional changes, we obtained
conidiation pattern shift libraries by Solexa/Illumina deep-sequencing
technology. A comparative analysis demonstrated that the expression of 137 genes
was up-regulated during the shift to normal conidiation, while the expression of
436 genes was up-regulated at the microcycle conidiation stage. A comparison of
subtractive libraries revealed that 83, 216, and 168 genes were related to
sucrose-induced, nitrate-induced, and phosphate-induced conidiation pattern
shifts, respectively. The expression of 217 genes whose expression was specific
to microcycle conidiation was further analyzed by the gene expression profiling
via multigene concatemers method using mRNA isolated from M. acridum grown on SYA
and the four normal conidiation media. The expression of 142 genes was confirmed
to be up-regulated on standard SYA medium. Of these 142 genes, 101 encode
hypothetical proteins or proteins of unknown function, and only 41 genes encode
proteins with putative functions. Of these 41 genes, 18 are related to cell
growth, 10 are related to cell proliferation, three are related to the cell
cycle, three are related to cell differentiation, two are related to cell wall
synthesis, two are related to cell division, and seven have other functions.
These results indicate that the conidiation pattern shift in M. acridum mainly
results from changes in cell growth and proliferation. CONCLUSIONS: The results
indicate that M. acridum shifts conidiation pattern from microcycle conidiation
to normal conidiation when there is increased sucrose, nitrate, or phosphate in
the medium during microcycle conidiation. The regulation of conidiation
patterning is a complex process involving the cell cycle and metabolism of M.
acridum. This study provides essential information about the molecular mechanism
of the induction of the conidiation pattern shift by single nutrients.
PMID- 27506835
TI - Functional and structural brain connectivity of young binge drinkers: a follow-up
study.
AB - Adolescence is a period of ongoing brain maturation characterized by hierarchical
changes in the functional and structural networks. For this reason, the young
brain is particularly vulnerable to the toxic effects of alcohol. Nowadays, binge
drinking is a pattern of alcohol consumption increasingly prevalent among
adolescents. The aim of the present study is to evaluate the evolution of the
functional and anatomical connectivity of the Default Mode Network (DMN) in young
binge drinkers along two years. Magnetoencephalography signal during eyes closed
resting state as well as Diffusion Tensor Imaging (DTI) were acquired twice
within a 2-year interval from 39 undergraduate students (22 controls, 17 binge
drinkers) with neither personal nor family history of alcoholism. The group
comparison showed that, after maintaining a binge drinking pattern along at least
two years, binge drinkers displayed an increased brain connectivity of the DMN in
comparison with the control group. On the other hand, the structural connectivity
did not show significant differences neither between groups nor over the time.
These findings point out that a continued pattern of binge drinking leads to
functional alterations in the normal brain maturation process, even before
anatomical changes can be detected.
PMID- 27506836
TI - Long-term Effects on Cognitive Trajectories of Postmenopausal Hormone Therapy in
Two Age Groups.
AB - Background: Postmenopausal hormone therapy may have long-term effects on
cognitive function depending on women's age. Methods: Postintervention follow-up
was conducted with annual cognitive assessments of two randomized controlled
clinical trial cohorts, beginning an average of 6-7 years after study medications
were terminated: 1,376 women who had enrolled in the Women's Health Initiative
when aged 50-54 years and 2,880 who had enrolled when aged 65-79 years. Women had
been randomly assigned to 0.625mg/d conjugated equine estrogens (CEE) for those
with prior hysterectomy (mean 7.1 years), CEE with 2.5mg/d medroxyprogesterone
acetate for those without prior hysterectomy (mean 5.4 years), or matching
placebos. Results: Hormone therapy, when prescribed to women aged 50-54 years,
had no significant long-term posttreatment effects on cognitive function and on
changes in cognitive function. When prescribed to older women, it was associated
with long-term mean (SE) relative decrements (standard deviation units) in global
cognitive function of 0.081 (0.029), working memory of 0.070 (0.025), and
executive function of 0.054 (0.023), all p < .05. These decrements were
relatively stable over time. Findings did not vary depending on the hormone
therapy regimen, prior use, or years from last menstrual period. Mean
intervention effects were small; however, the largest were comparable in
magnitude to those seen during the trial's active intervention phase.
Conclusions: CEE-based hormone therapy delivered near the time of menopause
provides neither cognitive benefit nor detriment. If administered in older women,
it results in small decrements in several cognitive domains that remain for many
years.
PMID- 27506837
TI - Pneumonia hospitalisations in Scotland following the introduction of pneumococcal
conjugate vaccination in young children.
AB - BACKGROUND: Scotland introduced PCV7 and PCV13 immunisation in young children in
2006 and 2010 respectively. One recent study from the United States reported a
decrease in hospitalisation rates for all-cause pneumonia most notably in adults
older than 75 years of age following PCV7 introduction in the US child
population. We aimed to examine the effect of PCV7 and PCV13 on hospitalisation
rates for all-cause pneumonia across all age groups in Scotland. METHODS: We
linked hospital records and death certification datasets for the entire Scottish
population for the period 2000 to 2012. We included all cases where the primary /
secondary diagnosis was pneumonia. Differences in hospital admission rates for
pneumonia by age group were calculated using the difference in average annual
rates for each period. RESULTS: We estimated that all-cause pneumonia
hospitalisation rates in children <2 years decreased by about 30 % in the post
PCV-13 period compared with the pre-PCV period. However, in adults aged 75-84
years and >=85 years, all-cause pneumonia hospitalisation rates increased by 63
and 46 % respectively in the post-PCV 13 period compared to the pre-PCV period.
This resulted in an additional 7000 hospitalisations across all age groups in
Scotland in 2012 about half of which were in adults >75 years. At the same time,
the median length of hospital stay decreased by a third in children <2 years and
by about 20 % in adults >75 years in the post-PCV13 period compared to the pre
PCV period. Additionally, there was an 11 % reduction in deaths due to all-cause
pneumonia, and 30 % reduction in pneumococcal hospitalisations across all age
groups in the post-PCV13 period compared with pre-PCV period. DISCUSSION: The
modest and sustained decline in the rates of hospitalisation for all-cause
pneumonia in children and the reduction in proportion of pneumonia
hospitalisations in children coded as pneumococcal disease in the post-PCV period
should alleviate concerns that pneumococcal serotype replacement may have
resulted in an increased pneumonia burden in this age group. The indirect impact
of child PCV immunisation in those not vaccinated (in terms of reduction in all
cause pneumonia hospitalisations in the elderly) has not been seen in Scotland.
Our results are likely to be confounded by changes in clinical coding and
healthcare practices over the same period. CONCLUSIONS: Our results illustrate
that health care planners cannot, with confidence, predict indirect PCV vaccine
impacts on hospitalisations. IPD surveillance across all age groups is needed to
assess the indirect effects of PCV in the community.
PMID- 27506839
TI - Hierarchical Mesoporous 3D Flower-like CuCo2O4/NF for High-Performance
Electrochemical Energy Storage.
AB - Ternary spinel CuCo2O4 nanostructure clenches great potential as high-performance
electrode material for next-generation energy storage systems because of its
higher electrical conductivity and electrochemical activity. Carbon free and
binder free 3D flower-like CuCo2O4 structure are grown on nickel foam (NF) via a
facile hydrothermal synthesis method followed by annealing. The obtained
CuCo2O4/NF is directly used as electrode for lithium ion batteries (LIBs) and
supercapacitors (SCs) application. The electrochemical study of 3D flower-like
CuCo2O4 as an electrode for LIB and SC shows highly mesoporous unique
architecture plays important role in achieving high capacity/capacitance with
superior cycle life. The high surface area and mesoporous nature not only offer
sufficient reaction sites, but also can accelerate the liquid electrolyte to
penetrate electrode and the ions to reach the reacting sites. In outcome, it
exhibits highest capacity of 1160 mA h g(-1) after 200 cycles when used as an
anode for LIB and specific capacitance of 1002 F g(-1) after 3000 cycles. The
superior electrochemical of synthesized material is attributed to direct contact
of electrode active material with good intrinsic electrical conductivity to the
underneath conductive NF substrate builds up an express path for fast ion and
electron transfer.
PMID- 27506838
TI - Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context
dependent manner.
AB - Histone modifications reflect gene activity, but the relationship between cause
and consequence of transcriptional control is heavily debated. Recent
developments in rewriting local histone codes of endogenous genes elucidated
instructiveness of certain marks in regulating gene expression. Maintenance of
such repressive epigenome editing is controversial, while stable reactivation is
still largely unexplored. Here we demonstrate sustained gene re-expression using
two types of engineered DNA-binding domains fused to a H3K4 methyltransferase.
Local induction of H3K4me3 is sufficient to allow re-expression of silenced
target genes in various cell types. Maintenance of the re-expression is achieved,
but strongly depends on the chromatin microenvironment (that is, DNA methylation
status). We further identify H3K79me to be essential in allowing stable gene re
expression, confirming its role in epigenetic crosstalk for stable reactivation.
Our approach uncovers potent epigenetic modifications to be directly written onto
genomic loci to stably activate any given gene.
PMID- 27506840
TI - [Revised WHO Classification of Tumours of the Central Nervous System:Summary of
the Revision and Perspective].
PMID- 27506841
TI - [Diagnosis and Treatment of Osteoporotic Thoracolumbar Vertebral Fracture].
PMID- 27506842
TI - [Rapid 3-Dimensional Models of Cerebral Aneurysm for Emergency Surgical
Clipping].
AB - We developed a method for manufacturing solid models of cerebral aneurysms, with
a shorter printing time than that involved in conventional methods, using a
compact 3D printer with acrylonitrile-butadiene-styrene(ABS)resin. We further
investigated the application and utility of this printing system in emergency
clipping surgery. A total of 16 patients diagnosed with acute subarachnoid
hemorrhage resulting from cerebral aneurysm rupture were enrolled in the present
study. Emergency clipping was performed on the day of hospitalization. Digital
Imaging and Communication in Medicine(DICOM)data obtained from computed
tomography angiography(CTA)scans were edited and converted to
stereolithography(STL)file formats, followed by the production of 3D models of
the cerebral aneurysm by using the 3D printer. The mean time from hospitalization
to the commencement of surgery was 242 min, whereas the mean time required for
manufacturing the 3D model was 67 min. The average cost of each 3D model was 194
Japanese Yen. The time required for manufacturing the 3D models shortened to
approximately 1 hour with increasing experience of producing 3D models. Favorable
impressions for the use of the 3D models in clipping were reported by almost all
neurosurgeons included in this study. Although 3D printing is often considered to
involve huge costs and long manufacturing time, the method used in the present
study requires shorter time and lower costs than conventional methods for
manufacturing 3D cerebral aneurysm models, thus making it suitable for use in
emergency clipping.
PMID- 27506843
TI - [Repeated Rupture of Bilateral Internal Carotid Artery Aneurysms in a Short
Period in Association with Polyarteritis Nodosa:A Case Report].
AB - Cerebral involvement is rare in polyarteritis nodosa(PAN);furthermore, secondary
intracranial hemorrhage due to cerebral aneurysm is extremely rare. We describe
an unusual case of repeated subarachnoid hemorrhage(SAH)in a 64-year-old woman
with a history of PAN. Initially, she developed severe headache(probable first
SAH, day 0), and presented at our hospital with second severe headache with
disturbed consciousness on day 6. Computed tomography(CT)revealed that SAH was
mainly distributed in the right basal cistern and sylvian fissure(second SAH).
Three aneurysms were detected using CT angiography on the bilateral internal
carotid arteries. An intentionally delayed surgery was planned because of the
high risk period of cerebral vasospasm and takotsubo cardiomyopathy. On day 15,
she complained of headache and had a convulsion. CT revealed a third SAH in the
left sylvian fissure;cerebral angiography revealed enlargement of the left
internal carotid-posterior communicating artery(IC-PC)aneurysm. Coil embolization
of the aneurysm was performed on day 16, and she was treated using
prednisolone(20mg/day)for PAN. However, on day 20, the patient became comatose,
and CT revealed a fourth SAH in the right sylvian fissure. Cerebral angiography
revealed enlargement of the right IC-PC aneurysm. Clipping of the aneurysm was
successfully performed in spite of ventricular dysfunction, and the dose of
prednisolone was increased to 40mg/day. After treatment, the ventricular
dysfunction gradually resolved. Cerebral aneurysms with PAN are candidates for
intervention because of their strong tendency to rupture. In our case, takotsubo
cardiomyopathy might have been associated with impairment of the coronary
microcirculation due to PAN. We suggest that aggressive immunosuppressive
treatment for PAN and curative treatments for cerebral aneurysms should be
considered with careful radiological examination and follow-up monitoring.
PMID- 27506844
TI - [Treatment of Non-Traumatic Spinal Epidural Hematoma:A Report of Five Cases and a
Systematic Review of the Literature].
AB - Objective:Non-traumatic spinal epidural hematoma(SEH)is relatively rare.
We report five cases of SEH, review the relevant literature, and discuss the
current treatment strategies for non-traumatic SEH in Japan.
Methods:Clinical data of cases with non-traumatic SEH treated at our
institute from 2008 to 2015 were retrospectively analyzed. In addition, we
identified the relevant literature using the Japan Medical Abstracts Society
databases for peer-reviewed articles published from Jan 1, 1995 to Aug 31, 2015.
The search terms "spinal", "epidural hematoma", and "non-traumatic OR
spontaneous" were used. Treatment strategies were summarized according to the
treatment criteria. Results:Five patients(1 man and 4 women;age, 59-86
years;mean age, 74 years)were treated for SEH. Hematomas were located in the
cervical(n=1), cervicothoracic(n=2), thoracic(n=1), and
thoracolumbar(n=1)regions. All patients suffered sudden neck and/or back pain
followed by subsequent neurological deterioration. Four patients were under
antithrombotic treatment, and underwent laminectomy and drainage of the hematoma
due to severe and progressive neurological deficits. All patients demonstrated
significant neurological recovery. Seventy-seven articles from domestic
institutes and hospitals were identified. Their criteria for conservative and
surgical treatments differed based on the time from the onset and severity.
Conclusion:Five cases of non-traumatic SEH were treated successfully.
Patients with moderate to severe neurological deficit need timely surgical
management, while non-surgical treatment may be indicated in mild deficits. To
standardize the optimal treatment for non-traumatic SEH, an appropriate
assessment system incorporating the time from onset and severity of neurological
impairment should be established.
PMID- 27506845
TI - [A Surgical Case of Tuberculoma with Visual Disturbance].
AB - We herein report a surgical case of multiple cerebral calculi located within the
chiasmatic cistern resulting in visual disturbance. A 61-year-old man experienced
homonymous lower right quadrantanopsia a few years prior. Non-enhanced head CT
revealed multiple calcified lesions of about 7-mm within the basal cistern. MRI
showed the lesion compressing the left optic tract. We could not remove the
entire lesion because of severe adhesion to the optic tract. A pathological test
showed calcified lesions with lymphocyte infiltration. We diagnosed tuberculoma
caused by tuberculous meningitis with degeneration of the calcified lesion
because of a history of tuberculosis at a fetal age. After the surgery, the
patient was discharged without improvement of the visual disturbance.
PMID- 27506846
TI - [Intramedullary Abscess of the Cervical Spinal Cord Caused by Advanced
Periodontitis:Case Report].
AB - We describe the case of a 60-year-old man with an intramedullary abscess of the
cervical spinal cord caused by advanced periodontitis. He suddenly developed
severe neck pain and rapidly progressive palsy of the left upper arm. T2-weighted
sagittal magnetic resonance imaging(MRI)revealed a hyperintense area extending
from C1 to C6. Gadolinium-enhanced T1-weighted MRI showed a ring-enhanced lesion
at the C3-4 level that was hyperintense on diffusion-weighted MRI. The patient
underwent drainage of the abscess through laminectomy. Cultures of the abscess
contents revealed Fusobacterium nucleatum and Peptostreptococcus
micros. Antibiotics administered to the patient to treat the infection with
these anaerobic bacteria improved the neurological deficit eight weeks after
surgery. The patient was also diagnosed with advanced periodontitis due to
Fusobacterium nucleatum that might have caused the intramedullary abscess
of the cervical spinal cord.
PMID- 27506848
TI - [Update Knowledge for Brain Tumors(9)Peripheral Nerve Tumor].
PMID- 27506847
TI - [Radiation-Induced Malignant Peripheral Nerve Sheath Tumor of the High Cervical
Spine].
AB - CASE: A 30-year-old woman presented with posterior cervical pain and left
sided omalgia. The patient had a history of non-Hodgkin's lymphoma for which she
had received prophylactic whole-brain irradiation(including at the upper cervical
level)17 years previously. A magnetic resonance imaging(MRI)scan obtained 1 month
previously showed an intradural extramedullary mass lesion at the left C1/2
level. We initially considered the tumor to be a benign schwannoma, but the
patient subsequently developed left hemiparesis and was consequently admitted 2
days after her first visit. A second MRI scan showed that the tumor had
progressed markedly. Hence, the patient underwent emergency surgical excision of
the tumor. However, the tumor could only be partially removed because it had
strongly adhered to the ventral aspect of the spinal cord. The tumor was
pathologically diagnosed as a malignant peripheral nerve sheath tumor(MPNST). The
residual tumor was subjected to local irradiation and surgery, but the treatment
was unsuccessful, and the patient died on the 91st day of her illness.
Conclusion:We report a case of radiation-induced high cervical MPNST
arising from a benign schwannoma. All 9 previously reported cases of radiation
induced spinal MPNST were reviewed. Intraspinal MPNST of the high cervical region
are extremely rare and are associated with a very poor prognosis. The 5-year
survival rate of such tumors is markedly worse than that of other types of MPNST,
and no standard treatment has been established for this condition.
PMID- 27506849
TI - SARAF modulates TRPC1, but not TRPC6, channel function in a STIM1-independent
manner.
AB - Canonical transient receptor potential-1 (TRPC1) is an almost ubiquitously
expressed channel that plays a relevant role in cell function. As other TRPC
members, TRPC1 forms receptor-operated cation channels that exhibit both STIM1
dependent and store-independent behaviour. The STIM1 inhibitor SARAF (for store
operated Ca2+ entry (SOCE)-associated regulatory factor) modulates SOCE by
interaction with the STIM1 region responsible for Orai1 activation (SOAR).
Furthermore, SARAF modulates Ca2+ entry through the arachidonate-regulated Ca2+
(ARC) channels, consisting of Orai1 and Orai3 heteropentamers and plasma membrane
resident STIM1. While a role for STIM1-Orai1-mediated signals has been
demonstrated, the possible role of SARAF in TRPC1 function remains unknown. Here,
we provide evidence for the interaction of SARAF with TRPC1, independently of
STIM1 both in STIM1-deficient NG115-401L cells and SH-SY5Y cells endogenously
expressing STIM1. Silencing of SARAF expression in STIM1-deficient cells
demonstrated that SARAF plays a negative regulatory role in TRPC1-mediated Ca2+
entry. The interaction of SARAF with TRPC1 in STIM1-deficient cells, as well as
with the TRPC1 pool not associated with STIM1 in STIM1-expressing cells was
enhanced by stimulation with the physiological agonist ATP. In contrast with
TRPC1, we found that the interaction between SARAF and TRPC6 was constitutive
rather than inducible by agonist stimulation. Furthermore, we found that SARAF
expression silencing was without effect on Ca2+ entry evoked by agonists in TRPC6
overexpressing cells, as well as in Ca2+ influx evoked by the TRPC6 activator
Hyp9. These findings provide evidence for a new regulator of TRPC1 channel
function and highlight the relevance of SARAF in intracellular Ca2+ homeostasis.
PMID- 27506850
TI - Purely endoscopic resection of pineal region tumors using infratentorial
supracerebellar approach: How I do it.
AB - BACKGROUND: Infratentorial supracerebellar approach via microscope still has some
limitations in resection of pineal region tumors. METHODS: The authors describe a
purely endoscopic infratentorial supracerebellar approach for resection of pineal
region tumors with matched air-driven arm and navigation. The lateral oblique
position is adopted. The same bimanual microsurgical techniques are utilized in
this endoscopic approach with panoramic view and satisfying comfort. CONCLUSIONS:
Purely endoscopic resection of pineal region tumors using infratentorial
supracerebellar approach is feasible. It may be considered as an alternative
approach for certain pineal region tumors.
PMID- 27506851
TI - Therapeutic Monoclonal Antibodies for the Treatment of Chronic Obstructive
Pulmonary Disease.
AB - Chronic obstructive pulmonary disease (COPD) is a disorder characterized by a
complex chronic inflammatory response that is largely poorly responsive to
treatment with corticosteroids. Consequently, there is a huge need to find
effective anti-inflammatory agents for the treatment of patients with this
disease. Inhibition of cytokines and chemokines or their receptors using
monoclonal antibodies (mAbs) could be a potential strategy to treat the
inflammatory component of COPD. In this article, we review the therapeutic
potential of some of these mAbs; however, to date there has been little or no
therapeutic effect of any mAb directed against cytokines or chemokines in
patients with COPD. This may reflect the complexity of COPD in which there is no
dominant role for any single cytokine or chemokine. It is also likely that since
the umbrella term COPD covers many endotypes having different underlying
mechanisms, mAbs directed towards specific cytokines or chemokines should be
tested in restricted and focused populations.
PMID- 27506853
TI - Mutuality, mobilization, and messaging for health promotion: Toward collective
cultural change.
PMID- 27506854
TI - The role of DOG1 immunohistochemistry in dermatopathology.
AB - BACKGROUND: This study was designed to evaluate the immunoexpression of DOG1, a
specific marker expressed in gastrointestinal stromal tumors, in normal skin
tissues and cutaneous epithelial tumors. METHODS: DOG1 immunostaining extent,
intensity and pattern were evaluated in 69 cutaneous apocrine/eccrine tumors, 11
sebaceous tumors, 46 follicular tumors, 52 keratinocytic tumors and perilesional
normal tissues. RESULTS: In normal tissues, DOG1 was expressed strongly in the
intercellular canaliculi of eccrine glands, moderately in the myoepithelial cells
of mammary and anogenital mammary-like glands, and weakly or not at all in the
periphery of sebaceous lobules and the lower layer of epidermis and follicular
infundibulum. All apocrine-type cutaneous mixed tumors showed apical-luminal
positivity for DOG1, and 4/9 of these tumors included intercellular canaliculi
highlighted by DOG1 immunostaining. Other sweat gland tumors, including
hidrocystadenoma, spiradenoma, cylindroma and apocrine carcinoma, also expressed
DOG1 focally with an apical-luminal pattern. Although slight membranous
positivity for DOG1 was observed in various tumor types, hidradenoma papilliferum
exhibited diffuse membranous DOG1 staining in the myoepithelial cells.
CONCLUSIONS: DOG1 is a novel marker for identifying intercellular canaliculi and
is a potential immunomarker of myoepithelial cells specific to mammary glands,
anogenital mammary-like glands and tumors originating therein.
PMID- 27506852
TI - Tetravalent Dengue Vaccine: A Review in the Prevention of Dengue Disease.
AB - Tetravalent, live-attenuated, dengue vaccine (Dengvaxia((r)); CYD-TDV) is the
first vaccine approved for the prevention of dengue disease caused by dengue
virus (DENV) serotypes 1-4 in individuals aged 9-45 or 9-60 years living in high
dengue endemic areas. This narrative review discusses the immunogenicity,
protective efficacy, reactogenicity and safety of CYD-TDV in the prevention of
dengue disease. In Latin American and Asian phase 3 trials in children and
adolescents (n > 30,000), the recommended three-dose CYD-TDV regimen was
efficacious in preventing virologically-confirmed dengue (VCD) during the period
from 28 days after the last dose (month 13) to month 25, meeting the primary
endpoint criteria. Protective efficacy against VCD in the respective individual
trials was 60.8 and 56.5 % (primary analysis). During the 25-month active
surveillance phase, CYD-TDV also provided protective efficacy against VCD, severe
dengue, any grade of dengue haemorrhagic fever and VCD-related hospitalization in
children aged 9 years and older. CYD-TDV was generally well tolerated, with no
safety concerns identified after up to 4 years' follow-up (i.e. from post dose 1)
in ongoing long-term studies. Based on evidence from the dengue clinical trial
program, the WHO SAGE recommended that countries with high dengue endemicity
consider introducing CYD-TDV as part of an integrated disease prevention strategy
to lower disease burden. Pharmacoeconomic considerations will be pivotal to
implementing dengue vaccination prevention strategies in these countries. The
availability of a dengue vaccine is considered essential if the 2012 WHO global
strategy targets for reducing the burden of dengue disease by 2020 are to be
attained. Hence, CYD-TDV represents a major advance for the prevention of dengue
disease in high dengue endemic regions.
PMID- 27506855
TI - Enemies with benefits: parasitic endoliths protect mussels against heat stress.
AB - Positive and negative aspects of species interactions can be context dependant
and strongly affected by environmental conditions. We tested the hypothesis that,
during periods of intense heat stress, parasitic phototrophic endoliths that
fatally degrade mollusc shells can benefit their mussel hosts. Endolithic
infestation significantly reduced body temperatures of sun-exposed mussels and,
during unusually extreme heat stress, parasitised individuals suffered lower
mortality rates than non-parasitised hosts. This beneficial effect was related to
the white discolouration caused by the excavation activity of endoliths. Under
climate warming, species relationships may be drastically realigned and
conditional benefits of phototrophic endolithic parasites may become more
important than the costs of infestation.
PMID- 27506857
TI - Prognostic factors of status epilepticus in adults.
AB - AIM: Status epilepticus (SE) can lead to sequelae or even death. Identifying
characteristics associated with poor outcome is crucial in guiding patient
treatment. Based on our retrospective patient cohorts, potential prognostic
factors were analysed. METHODS: Patients consecutively treated for refractory
convulsive status epilepticus (CSE) between 2001 and 2010 and non-convulsive
status epilepticus (NCSE) between 2004 and 2009 were studied. Outcome was
compared to prognostic variables. Index SE episodes were used for the statistical
analyses. Crosstabs and independent samples t-test were applied. Due to sample
size, logistic regression was performed for the combined groups. RESULTS: In
total, 50% (9/18) of index refractory CSE and 42% (16/38) of index NCSE episodes
led to sequelae. Refractory CSE requiring narcosis for >20 hours was associated
with poor outcome (p=0.05). De novo presentation (p=0.0001), long-lasting SE (>2
hours) (p=0.014), age >65 years (p=0.002), and refractory SE (p=0.047) were
predictors of poor outcome following NCSE. Based on logistic regression for
combined refractory CSE and NCSE, de novo presentation was identified as the
strongest predictor of sequelae. CONCLUSIONS: Older age and de novo SE are
predictors of sequelae following NCSE. Prolonged SE is a risk factor for poor
outcome, both for refractory CSE and NCSE. Aggressive initial treatment to
terminate seizures during the early phase is therefore essential.
PMID- 27506856
TI - Marine and giant viruses as indicators of a marine microbial community in a
riverine system.
AB - Viral communities are important for ecosystem function as they are involved in
critical biogeochemical cycles and controlling host abundance. This study
investigates riverine viral communities around a small rural town that influences
local water inputs. Myoviridae, Siphoviridae, Phycodnaviridae, Mimiviridae,
Herpesviridae, and Podoviridae were the most abundant families. Viral species
upstream and downstream of the town were similar, with Synechoccocus phage,
salinus, Prochlorococcus phage, Mimivirus A, and Human herpes 6A virus most
abundant, contributing to 4.9-38.2% of average abundance within the metagenomic
profiles, with Synechococcus and Prochlorococcus present in metagenomes as the
expected hosts for the phage. Overall, the majority of abundant viral species
were or were most similar to those of marine origin. At over 60 km to the river
mouth, the presence of marine communities provides some support for the Baas
Becking hypothesis "everything is everywhere, but, the environment selects." We
conclude marine microbial species may occur more frequently in freshwater systems
than previously assumed, and hence may play important roles in some freshwater
ecosystems within tens to a hundred kilometers from the sea.
PMID- 27506858
TI - Can knowledge-based N management produce more staple grain with lower greenhouse
gas emission and reactive nitrogen pollution? A meta-analysis.
AB - Knowledge-based nitrogen (N) management, which is designed for a better
synchronization of crop N demand with N supply, is critical for global food
security and environmental sustainability. Yet, a comprehensive assessment on how
these N management practices affect food production, greenhouse gas emission
(GHG), and N pollution in China is lacking. We compiled the results of 376
studies (1166 observations) to evaluate the overall effects of seven knowledge
based N management practices on crop productivity, nitrous oxide (N2 O) emission,
and major reactive N (Nr) losses (ammonia, NH3 ; N leaching and runoff), for
staple grain (rice, wheat, and corn) production in China. These practices
included the application of controlled-release N fertilizer, nitrification
inhibitor (NI) and urease inhibitor (UI), higher splitting frequency of
fertilizer N application, lower basal N fertilizer (BF) proportion, deep
placement of N fertilizer, and optimal N rate based on soil N test. Our results
showed that, compared to traditional N management, these knowledge-based N
practices significantly increased grain yields by 1.3-10.0%, which is attributed
to the higher aboveground N uptake (5.1-12.1%) and N use efficiency in grain (8.0
48.2%). Moreover, these N management practices overall reduced GHG emission and
Nr losses, by 5.4-39.8% for N2 O emission, 30.7-61.5% for NH3 emission (except
for the NI application), 13.6-37.3% for N leaching, and 15.5-45.0% for N runoff.
The use of NI increased NH3 emission by 27.5% (9.0-56.0%), which deserves extra
attention. The cost and benefit analysis indicated that the yield profit of these
N management practices exceeded the corresponding input cost, which resulted in a
significant increase of the net economic benefit by 2.9-12.6%. These results
suggest that knowledge-based N management practice can be considered an effective
way to ensure food security and improve environmental sustainability, while
increasing economic return.
PMID- 27506859
TI - Discussion.
PMID- 27506860
TI - Rural risk: Geographic disparities in trauma mortality.
AB - BACKGROUND: Barriers to trauma care for rural populations are well documented,
but little is known about the magnitude of urban-rural disparities in injury
mortality. This study sought to quantify differences in injury mortality
comparing rural and nonrural residents with traumatic injuries. METHODS: Using
data from the 2009-2010 Nationwide Emergency Department Sample, multiple logistic
regression analyses were conducted to estimate odds of death after traumatic
injury for rural residents compared with nonrural residents, while controlling
for age, sex, injury type and severity, comorbidities, trauma designation, and
Census region. RESULTS: Rural residents were 14% more likely to die after
traumatic injury compared with nonrural residents (P < .001). Increased odds of
death for rural residents were observed at level I (odds ratio = 1.20, P < .001),
level II (odds ratio = 1.34, P < .001), and level IV/nontrauma centers (odds
ratio = 1.23, P < .001). The disparity was greatest for injuries occurring in the
South and Midwest (odds ratio = 1.54, P < .001 and odds ratio = 2.06, P < .001,
respectively) and for cases with an injury severity score <9 or unknown severity
(odds ratio = 2.09, P < .001 and odds ratio = 1.31, P < .001, respectively).
CONCLUSION: Rural residents are significantly more likely than nonrural residents
to die after traumatic injury. This disparity varies by trauma center
designation, injury severity, and US Census region. Distance and time to
treatment likely play a role in rural injury outcomes, along with regional
differences in prehospital care and trauma system organization.
PMID- 27506861
TI - An unusual, life-threatening camel bite to the abdomen of a young man.
PMID- 27506862
TI - Discussion.
PMID- 27506864
TI - Discussion.
PMID- 27506863
TI - Comparative characteristics of primary hyperparathyroidism in pediatric and young
adult patients.
AB - BACKGROUND: Primary hyperparathyroidism is rare in pediatric patients. Our study
aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young
adult (19-29 years) patients. METHODS: A prospectively collected database from a
single, high-volume institution was queried for all patients age <30 years who
had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546
(2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87
young adult patients. Presenting symptoms, operative data, and postoperative
course were compared for patients age 0-19 years and 20-29 years. RESULTS:
Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often
in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among
patients with hereditary primary hyperparathyroidism, multiple endocrine
neoplasia type 1 was the most common type. Multiglandular disease was common in
both pediatric (30.7%) and young adult (21.8%) patients. Following
parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none
had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months
was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P =
.44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of
recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple
endocrine neoplasia 1-related primary hyperparathyroidism in all cases.
CONCLUSION: Although primary hyperparathyroidism is sporadic in most patients <19
years, they are more likely to have multiple endocrine neoplasia type 1
associated primary hyperparathyroidism (23%). Parathyroidectomy for primary
hyperparathyroidism can be performed safely in pediatric patients with a high
rate of cure. Follow-up for patients with hereditary disease is necessary.
PMID- 27506865
TI - MiR-30c-2* negative regulated MTA-1 expression involved in metastasis and drug
resistance of HPV-infected non-small cell lung cancer.
AB - BACKGROUND: MiR-30c-2* is considered to be a tumor suppressor microRNA in various
cancers and is associated with gemcitabine sensitivity of lung cancer cells.
Downregulation of miR-30c-2* promotes tumor invasion via increased expression of
metastasis-associated protein-1. We hypothesized that downregulated expression of
miR-30c-2* was involved in human papillomavirus-associated lung tumorigenesis and
drug resistance. METHODS: We examined whether expression of human papillomavirus
16/18 oncoprotein and miR-30c-2*-associated genes could be linked to patient
outcome by collecting 319 lung tumors from patients with non-small cell lung
cancer to determine expression of human papillomavirus 16/18 E6 protein, miR-30c
2*, and miR-30c-2* downstream metastasis-associated protein-1 mRNA by
immunohistochemical and real-time polymerase chain reaction analysis. RESULTS:
Our results showed that miR-30C-2* levels were increased 45-fold in the E6
knockdown TL-1 cells when compared with levels in the parental cells. More
interestingly, metastasis-associated protein-1 expression correlated negatively
with miR-30C-2* and positively with human papillomavirus 16 E6 protein expression
in lung tumors from lung cancer patients. Metastasis-associated protein-1
expression levels in the tumor tissues correlated positively with tumor stage and
nodal metastasis. Patients with high metastasis-associated protein-1 expression,
and especially patients infected with human papillomavirus, experienced a poor
clinical outcome, tumor recurrence, and a poor therapeutic response compared with
those with low metastasis-associated protein-1 expression. CONCLUSION: These
results showed that miR-30C-2* and levels of downstream metastasis-associated
protein-1 gene expression in the tumor tissues of patients could be useful in
predicting clinical outcome and therapeutic response and in selecting useful
therapeutic drugs for lung cancer patients, especially patients with human
papillomavirus infection.
PMID- 27506866
TI - Live tissue versus simulation training for emergency procedures: Is simulation
ready to replace live tissue?
AB - BACKGROUND: Training of emergency procedures is challenging and application is
not routine in all health care settings. The debate over simulation as an
alternative to live tissue training continues with legislation before Congress to
banish live tissue training in the Department of Defense. Little evidence exists
to objectify best practice. We sought to evaluate live tissue and simulation
based training practices in 12 life-saving emergency procedures. METHODS: In the
study, 742 subjects were randomized to live tissue or simulation-training.
Assessments of self-efficacy, cognitive knowledge, and psychomotor performance
were completed pre- and post-training. Affective response to training was
assessed through electrodermal activity. Subject matter experts gap analysis of
live tissue versus simulation completed the data set. RESULTS: Subjects
demonstrated pre- to post-training gains in self-efficacy, cognitive knowledge,
psychomotor performance, and affective response regardless of training modality
(P < .01 each). With the exception of fluid resuscitation in the psychomotor
performance domain, no statistically significant differences were observed based
on training modality in the overall group. Risk estimates on the least pretest
performance subgroup favored simulation in 7 procedures. Affective response was
greatest in live tissue training (P < .01) and varied by species and model.
Subject matter experts noted significant value in live tissue in 7 procedures.
Gap analysis noted shortcomings in all models and synergy between models.
CONCLUSION: Although simulation has made significant gains, no single modality
can be identified definitively as superior. Wholesale abandonment of live tissue
training is not warranted. We maintain that combined live tissue and simulation
based training add value and should be continued. Congressional mandates may
accelerate simulation development and improve performance.
PMID- 27506867
TI - Fifteen-year experience with renal cell carcinoma with associated venous tumor
thrombus.
AB - BACKGROUND: For patients with renal cell carcinoma with venous tumor thrombus
(VTT), the importance of the extent of the VTT on survival has inconsistent
published results. The aim of the study was to evaluate the prognostic value of
the VTT on morbidity and mortality of our patients with renal cell carcinoma.
METHODS: This was a single institution review of all patients who underwent
resection of renal cell carcinoma with VTT over a 15-year period. RESULTS: Thirty
seven patients (26 men, 11 women) with a mean age of 61 years were analyzed. The
majority of the cohort were of Neves level II (n = 19), while 8 were of Neves 0
(only renal vein) or I, and 10 were of Neves III (extending into retrohepatic
cava) or IV (extending supradiaphragmatically). When compared with Neves 0-II
patients, there were more Neves III-IV patients with operative time >3 hours (70%
vs 30%), blood loss >2,000 mL (70% vs 33%), and intensive care unit stay longer
than one day (60% vs 30%) (P <= .05 each). Mean follow-up was 58 months. The
overall 5-year survival was 71%, and all 10 patients with Neves III-IV had
survived since the operation. CONCLUSION: We found advanced tumor thrombus
involvement did not impact long-term survival; however, cases with suprahepatic
VTT had increased operative time, blood loss, and duration of hospital stay.
PMID- 27506868
TI - Leptospirosis Presenting with Rapidly Progressing Acute Renal Failure and
Conjugated Hyperbilirubinemia: A Case Report.
AB - BACKGROUND Unexplained renal insufficiency combined with hepatic failure is a
common problem encountered by clinicians. As with many disease processes
involving multi-organ systems, reversible causes are usually not readily
identifiable, and for many patients their health deteriorates rapidly. We present
a rare cause of acute renal failure and hyperbilirubinemia occurring
simultaneously, with leptospirosis presenting as Weil's disease. CASE REPORT A 53
year-old male presented to our clinic with complaints of anuria over the past two
days. His symptoms started with dark urine, severe cramps in the thighs, and
chills. The patient was a visitor to the United States from Guyana. Positive
physical examination findings included mild tachycardia and hypotension, scleral
icterus, and tenderness over abdomen, costovertebral angles, and thighs. The
patient had a high white blood cell count, thrombocytopenia, renal/hepatic
insufficiency, and an urinary tract infection (UTI). The patient was initially
treated under the suspicion of acute kidney injury secondary to rhabdomyolysis
and pyelonephritis. The patient continued to deteriorate with decreasing platelet
counts, worsening renal function, hyperbilirubinemia, and respiratory distress,
with no improvement with hemodialysis. Broad-spectrum antibiotics were
administered, including doxycycline, due to a high suspicion of leptospirosis.
The patient's condition drastically improved after initiation of doxycycline. On
subsequent days, the patient's Leptospira antibody results were available,
showing titers of more than 1:3200. Hemodialysis was discontinued as the patient
started producing urine with improved kidney function. CONCLUSIONS As world
travel becomes more economically feasible, we will continue to encounter foreign
endemic diseases. Leptospirosis presenting as Weil's disease is a common cause of
renal and hyperbilirubinemia in endemic areas. Often, as was the case for our
patient where the time from presentation to acute respiratory distress syndrome
(ARDS) was 72 hours, the diagnosis evolves over the course of several days.
Antibody testing often takes time and delays in treatment can cause rapid
clinical deterioration. In such cases, we recommend beginning empiric treatment
before confirmation of laboratory tests.
PMID- 27506869
TI - Analysis of the efficiency of recombinant Escherichia coli strain cultivation in
a gas-vortex bioreactor.
AB - The levels of aeration and mass transfer are critical parameters required for an
efficient aerobic bioprocess, and directly depend on the design features of
exploited bioreactors. A novel apparatus, using gas vortex for aeration and mass
transfer processes, was constructed in the Center of Vortex Technologies
(Novosibirsk, Russia). In this paper, we compared the efficiency of recombinant
Escherichia coli strain cultivation using novel gas-vortex technology with
conventional bioprocess technologies such as shake flasks and bioreactors with
mechanical stirrers. We demonstrated that the system of aeration and agitation
used in gas-vortex bioreactors provides 3.6 times higher volumetric oxygen
transfer coefficient in comparison with mechanical bioreactor. The use of gas
vortex bioreactor for recombinant E. coli strain cultivation allows to increase
the efficiency of target protein expression at 2.2 times for BL21(DE3)/pFK2
strain and at 3.5 times for auxotrophic C600/pRT strain (in comparison with
stirred bioreactor).
PMID- 27506870
TI - Introduction: Metal Hydrides.
PMID- 27506871
TI - Multi-target therapeutics for neuropsychiatric and neurodegenerative disorders.
AB - Historically, neuropsychiatric and neurodegenerative disease treatments focused
on the 'magic bullet' concept; however multi-targeted strategies are increasingly
attractive gauging from the escalating research in this area. Because these
diseases are typically co-morbid, multi-targeted drugs capable of interacting
with multiple targets will expand treatment to the co-morbid disease condition.
Despite their theoretical efficacy, there are significant impediments to clinical
success (e.g., difficulty titrating individual aspects of the drug and
inconclusive pathophysiological mechanisms). The new and revised diagnostic
frameworks along with studies detailing the endophenotypic characteristics of the
diseases promise to provide the foundation for the circumvention of these
impediments. This review serves to evaluate the various marketed and nonmarketed
multi-targeted drugs with particular emphasis on their design strategy.
PMID- 27506872
TI - Recent advances in cancer drug discovery targeting RAS.
AB - Mutated RAS is present in 30% of human tumors, appearing in 90% of pancreatic,
45% of colon and 35% of lung cancers. These high occurrences make RAS one of the
most important drug targets in oncology. Three decades of effort to target RAS
have been unsuccessful in generating drug therapies suggesting that it might
represent an 'undruggable' target. However, recent reports highlighting new
approaches for targeting RAS have uncovered more information on protein structure
and identified new binding pockets. Efforts to target the KRAS G12C mutation
specifically have shown promising results whereas other approaches have targeted
various protein complexes. These advances could lead to development of new
effective cancer drugs targeting RAS.
PMID- 27506873
TI - Structural features of subtype-selective EP receptor modulators.
AB - Prostaglandin E2 is a potent endogenous molecule that binds to four different G
protein-coupled receptors: EP1-4. Each of these receptors is a valuable drug
target, with distinct tissue localisation and signalling pathways. We review the
structural features of EP modulators required for subtype-selective activity, as
well as the structural requirements for improved pharmacokinetic parameters.
Novel EP receptor subtype selective agonists and antagonists appear to be
valuable drug candidates in the therapy of many pathophysiological states,
including ulcerative colitis, glaucoma, bone healing, B cell lymphoma,
neurological diseases, among others, which have been studied in vitro, in vivo
and in early phase clinical trials.
PMID- 27506874
TI - Predisposing factors, pathogenesis and therapeutic intervention of Kawasaki
disease.
AB - Kawasaki disease (KD) is an acute febrile childhood inflammatory disease,
associated with coronary artery abnormalities. The disease is believed to result
from an aberrant inflammatory response to an infectious trigger in a genetically
predisposed individual. KD is associated with an endothelial cell injury as a
consequence of T cell activation and cytotoxic effects of various proinflammatory
cytokines. Intravenous immunoglobulin (IVIG) infusion and aspirin are the
standard treatment of acute KD. However, 10-20% of patients show resistance to
IVIG therapy and present higher risk of coronary vasculitis. The relative roles
of second IVIG infusion, corticosteroids, calcineurin inhibitors, interleukin-1
antagonists and anti-tumor necrosis factor agents remain uncertain. In this
review, we highlight the predisposing factors, pathogenesis and therapeutic
intervention of KD, particularly new therapeutics for IVIG-resistant patients.
PMID- 27506875
TI - Unprecedented Disease-Related Coral Mortality in Southeastern Florida.
AB - Anomalously high water temperatures, associated with climate change, are
increasing the global prevalence of coral bleaching, coral diseases, and coral
mortality events. Coral bleaching and disease outbreaks are often inter-related
phenomena, since many coral diseases are a consequence of opportunistic pathogens
that further compromise thermally stressed colonies. Yet, most coral diseases
have low prevalence (<5%), and are not considered contagious. By contrast, we
document the impact of an extremely high-prevalence outbreak (61%) of white
plague disease at 14 sites off southeastern Florida. White-plague disease was
observed near Virginia Key, Florida, in September 2014, and after 12 months had
spread 100 km north and 30 km south. The disease outbreak directly followed a
high temperature coral-bleaching event and affected at least 13 coral species.
Eusmilia fastigiata, Meandrina meandrites, and Dichocoenia stokesi were the most
heavily impacted coral species, and were reduced to <3% of their initial
population densities. A number of other coral species, including Colpophyllia
natans, Pseudodiploria strigosa, Diploria labyrinthiformis, and Orbicella
annularis were reduced to <25% of their initial densities. The high prevalence of
disease, the number of susceptible species, and the high mortality of corals
affected suggests this disease outbreak is arguably one of the most lethal ever
recorded on a contemporary coral reef.
PMID- 27506876
TI - NanoSIMS chemical imaging combined with correlative microscopy for biological
sample analysis.
AB - Nano-scale Secondary Ion Mass Spectrometry (NanoSIMS) is one of the most powerful
in situ elemental and isotopic analysis techniques available to biologists. The
combination of stable isotope probing with NanoSIMS (nanoSIP) has opened up new
avenues for biological studies over the past decade. However, due to limitations
inherent with any analytical methodology, additional information from correlative
techniques is usually required to address real biological questions. Here we
review recent developments in correlative analysis applied to complex biological
systems: first, high-resolution tracking of molecules (e.g. peptides, lipids) by
correlation with electron microscopy and atomic force microscopy; second,
identification of a specific microbial taxon with fluorescence in situ
hybridization and quantification of its metabolic capacities; and, third,
molecular specific imaging with new probes.
PMID- 27506879
TI - N-Hydroxyphthalimide: a new photoredox catalyst for [4+1] radical cyclization of
N-methylanilines with isocyanides.
AB - The first utilization of N-hydroxyphthalimide (NHPI) as an organophotoredox
catalyst is demonstrated by the [4+1] radical cyclization reaction of N
methylanilines with isocyanides. The protocol offers an operationally simple one
pot synthesis of 3-iminodihydroindoles at room temperature.
PMID- 27506878
TI - Association between angiotensin converting enzyme gene insertion/deletion
polymorphism and renal scar risk in children vesicoureteral reflex: a reappraise
meta-analysis.
AB - Vesicoureteral reflex(VUR) is a common disease in children. Some studies
indicated that the angiotensin converting enzyme (ACE) gene insertion/deletion
(I/D) polymorphism associated with the renal scar in VUR, but not all researchers
agreed with it. To clarify the effect of ACE I/D polymorphism on renal scar risk
in children with VUR, we performed the present meta-analysis. PubMed, CNKI, CBM,
and Embase databases were searched for studies that examined the relationship
between ACE I/D polymorphism and renal scar risk in children with VUR. The Stata
12.0 software was used for statistical analyses. 11 case-control studies with
1,032 VUR patients were analyzed. The results showed that the DD genotype and D
allele were associated with renal scar risk in overall VUR patients, DD vs. DI +
II: OR = 1.61, 95% CI = 1.04-2.49, P = 0.03; DD vs. II: OR = 1.78, 95% CI = 1.20
2.65, P < 0.01; D vs. I: OR = 1.38, 95% CI = 1.02-1.86, P = 0.04. Similar results
were revealed in Turks, but not in Caucasians and Asians. Our meta-analysis
indicated that the ACE DD genotype may increase the risk of renal scar in
children with VUR.
PMID- 27506880
TI - Epicardial Adipose Tissue Contributes to the Development of Non-Calcified
Coronary Plaque: A 5-Year Computed Tomography Follow-up Study.
AB - AIM: Epicardial adipose tissue (EAT) has been suggested as a contributing factor
for coronary atherosclerosis based on the previous cross-sectional studies and
pathophysiologic background. However, a causal relationship between EAT and the
development of non-calcified coronary plaque (NCP) has not been investigated.
METHODS: A total of 122 asymptomatic individuals (age, 56.0+/-7.6 years; male,
80.3%) without prior history of coronary artery disease (CAD) or metabolic
syndrome and without NCP or obstructive CAD at baseline cardiac computed
tomography (CT) were enrolled. Repeat cardiac CT was performed with an interval
of more than 5 years. Epicardial fat volume index (EFVi; cm3/m2) was assessed in
relation to the development of NCP on the follow-up CT where the results were
classified into "calcified plaque (CP)," "no plaque," and "NCP" groups. RESULTS:
On the follow-up CT performed with a median interval of 65.4 months, we observed
newly developed NCP in 24 (19.7%) participants. Baseline EFVi was significantly
higher in the NCP group (79.9+/-30.3 cm3/m2) than in the CP group (63.7+/-22.7
cm3/m2; P=0.019) and in the no plaque group (62.5+/-24.7 cm3/m2; P=0.021).
Multivariable logistic regression analysis demonstrated that the presence of
diabetes (OR, 9.081; 95% CI, 1.682-49.034; P=0.010) and the 3rd tertile of EFVi
(OR, 4.297; 95% CI, 1.040-17.757; P=0.044 compared to the 1st tertile) were the
significant predictors for the development of NCP on follow-up CT. CONCLUSIONS:
Greater amount of EAT at baseline CT independently predicts the development of
NCP in asymptomatic individuals.
PMID- 27506881
TI - The plasma membrane monoamine transporter (PMAT): Structure, function, and role
in organic cation disposition.
AB - Plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation
transporter that transports a variety of biogenic amines and xenobiotic cations.
Highly expressed in the brain, PMAT represents a major uptake2 transporter for
monoamine neurotransmitters. At the blood-cerebrospinal fluid (CSF) barrier, PMAT
is the principal organic cation transporter for removing neurotoxins and drugs
from the CSF. Here I summarize our latest understanding of PMAT and its roles in
monoamine uptake and xenobiotic disposition.
PMID- 27506884
TI - Adult Neurology Training Schedule is Important, Not Just the Length.
PMID- 27506882
TI - Serum Autotaxin is a Marker of the Severity of Liver Injury and Overall Survival
in Patients with Cholestatic Liver Diseases.
AB - Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have
recently been linked to cholestatic pruritus and liver injury. We aimed to
investigate whether ATX is an indicator of cholestatic liver injury, health
related quality of life (HRQoL) and prognosis based on a group of 233 patients,
118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing
cholangitis (PSC). Patients were followed for 1-60 months, cumulative survival
rates were calculated. ATX activity was significantly higher in both groups than
in the 103 controls, particularly in patients with cirrhosis and in patients with
longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC
exhibited increased ATX activity. ATX activity was correlated with liver
biochemistry, MELD, Mayo Risk scores and was associated with worse disease
specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was
a negative predictor of survival. Increased ATX levels were associated with a 4
fold higher risk of death/liver transplantation in patients with PBC and a 2.6
fold higher risk in patients with PSC. We conclude that in patients with
cholestatic conditions, ATX is not only associated with pruritus but also
indicates impairment of other HRQoL aspects, liver dysfunction, and can serve as
a predictor of survival.
PMID- 27506885
TI - Purification and identification of amylases released by the human pathogen
Trichomonas vaginalis that are active towards glycogen.
AB - The parasitic protist Trichomonas vaginalis is the causative agent of the
sexually transmitted infection trichomoniasis. In the laboratory, T. vaginalis is
typically cultured in a serum-containing medium with maltose or glucose as the
carbon source. The nature of the carbohydrates used by the organism in the
environment of its host is unclear. However, the vagina contains substantial
amounts of glycogen, which is believed to provide a growth substrate for the
vaginal microbiota. We have shown previously that T. vaginalis releases
glucosidases that are active towards glycogen into its environment. Here we
purify and identifying these glucosidases. Using ammonium sulfate precipitation
and precipitation with ethanol/glycogen, we purified glucosidase activity from
conditioned growth medium, achieving over 300-fold enrichment. Maltose was
released when glycogen was incubated with the glucosidase preparation, indicating
that a beta-amylase was present. However, after prolonged incubation, small
quantities of larger products including maltotriose were obtained. Liquid
chromatography and tandem mass spectrometry showed that the glucosidase
preparation contained three proteins, the major component being a putative beta
amylase encoded by the TVAG_080000 open reading frame. Lesser amounts of two
putative alpha-amylases, encoded by the TVAG_178580 and TVAG_205920 open reading
frames, were also present. We cloned and expressed the TVAG_080000 open reading
frame and found that the recombinant protein was capable of digesting glycogen,
releasing exclusively maltose. We conclude that T. vaginalis releases a variety
of amylases into its growth environment and is well equipped to utilize the
glycogen found in the vagina as a source of essential carbohydrates.
PMID- 27506886
TI - Antioxidant activity in vitro and in vivo of the polysaccharides from different
varieties of Auricularia auricula.
AB - In this study, five different kinds of polysaccharides (AAP1, AAP2, AAP3, AAP4,
and AAP5) were extracted from different varieties of Auricularia auricula through
an alkali extraction process. Furthermore, the crude polysaccharides were
deproteinized by the Sevag method. Auricularia auricula produced in the Shanxi
province had the highest content of polysaccharide, 53.02%. The monosaccharide
composition was determined by the GC method. Their antioxidant capacities in
vitro were assessed by radical-scavenging capacity (DPPH, superoxide, and
hydroxyl radicals), metal chelating ability and reducing-power methods. In
addition, the evaluation of their antioxidant effects in vivo was performed using
the C. elegans model. The yield of crude polysaccharides, monosaccharide
composition and antioxidant activity of Auricularia auricula polysaccharides
(AAPs) were different among samples from various sources. Among them, the
strongest antioxidant activity was shown for AAP1, consisting of arabinose,
xylose, 2-deoxy-d-glucose, mannose, glucose, and N-acetyl-d-glucosamine with the
molar ratio of 1 : 0.44 : 0.33 : 1.67 : 1 : 0.17. It could scavenge free
radicals, up-regulate stress-resistance-related enzymes including superoxide
dismutase (SOD) by 70.04 +/- 8.75% and CAT by 117.32 +/- 8.06% and reduce the
level of reactive oxygen species (ROS) in C. elegans under oxidative stress. The
present results suggested that variety was an important factor that affects the
antioxidant activity of A. auricula polysaccharides.
PMID- 27506887
TI - Fresh Perspectives from Emerging Experts.
PMID- 27506888
TI - Primary percutaneous coronary intervention in octogenarians.
AB - BACKGROUND: Limited data are available on the outcome of primary percutaneous
coronary intervention (PCI) in octogenarian patients, as the elderly are under
represented in randomized trials. This study aims to provide insights on clinical
characteristics, management and outcome of the elderly and very elderly
presenting with STEMI. METHODS: 2225 STEMI patients >=70years old (mean age
76.8+/-5.1years and 53.8% men) were admitted into the network of the ISACS-TC
registry. Of these patients, 72.8% were >=70 to 79years old (elderly) and 27.2%
were >=80years old (very-elderly). The primary end-point was 30-day mortality.
RESULTS: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the
very-elderly. Primary PCI decreased the unadjusted risk of death both in the
elderly (OR: 0.32, 95% CI: 0.24-0.43) and very-elderly patients (OR: 0.45, 95% CI
0.30-0.68), without significant difference between groups. In the very-elderly
hypertension and Killip class >=2 were the only independent factors associated
with mortality; whereas in the elderly female gender, prior stroke, chronic
kidney disease and Killip class >=2 were all factors independently associated
with mortality. Factors associated with the lack of use of reperfusion were
female gender and atypical chest pain in the very-elderly and in the elderly; in
the elderly, however, there were some more factors, namely: history of diabetes,
current smoking, prior stroke, Killip class >=2 and history chronic kidney
disease. CONCLUSIONS: Age is relevant in the prognosis of STEMI, but its
importance should not be considered secondary to other major clinical factors.
Primary PCI appears to have beneficial effects in the octogenarian STEMI
patients.
PMID- 27506889
TI - High glycaemia and low uptake of insulin treatment among remote Torres Strait
Islanders with diabetes: Implications for service delivery.
PMID- 27506890
TI - Close encounters of the type-six kind: injected bacterial toxins modulate gut
microbial composition.
PMID- 27506892
TI - Bmal1 induces osteoblast differentiation via regulation of BMP2 expression in
MC3T3-E1 cells.
AB - AIMS: Mammalian circadian rhythms regulate many metabolic processes. Recent
studies suggest that brain and muscle Arnt-like 1 (BMAL1), an important component
of mammalian circadian rhythm, is associated with insulin signaling. Several
studies have shown that insulin is associated with bone metabolism; however, the
relationship between BMAL1 and osteoblasts remains unclear. MAIN METHODS:
Expression of osteogenic markers and Bmal1 in MC3T3-E1 cells was measured by RT
PCR and Western blotting. Alizarin red S staining was performed to assess matrix
mineralization in MC3T3-E1 cells. KEY FINDINGS: mRNA levels of osteogenic genes
and Bmal1 were up-regulated in MC3T3-E1 cells upon insulin treatment. In
addition, Bmal1 overexpression increased the expression of osteogenic genes
including inhibitor of DNA binding (Id1), Runt-related transcription factor 2
(Runx2), and osteocalcin (OC). Interestingly, expression of Bone morphogenetic
protein-2 (BMP2), an important upstream factor of Id1, Runx2, and OC, was
markedly increased by Bmal1. Finally, we confirmed that insulin-induced BMP2
expression was attenuated in Bmal1 knockout (KO) cells. PCR analysis and alizarin
red S staining showed that insulin-mediated increases gene expression and calcium
deposition were reduced in Bmal1 KO cells compared to wild-type cells.
SIGNIFICANCE: Taken together, these results demonstrate that Bmal1 promotes
osteoblast differentiation by regulating BMP2 expression in MC3T3-E1 cells.
PMID- 27506891
TI - Capture-C reveals preformed chromatin interactions between HIF-binding sites and
distant promoters.
AB - Hypoxia-inducible factor (HIF) directs an extensive transcriptional cascade that
transduces numerous adaptive responses to hypoxia. Pan-genomic analyses, using
chromatin immunoprecipitation and transcript profiling, have revealed large
numbers of HIF-binding sites that are generally associated with hypoxia-inducible
transcripts, even over long chromosomal distances. However, these studies do not
define the specific targets of HIF-binding sites and do not reveal how induction
of HIF affects chromatin conformation over distantly connected functional
elements. To address these questions, we deployed a recently developed chromosome
conformation assay that enables simultaneous high-resolution analyses from
multiple viewpoints. These assays defined specific long-range interactions
between intergenic HIF-binding regions and one or more promoters of hypoxia
inducible genes, revealing the existence of multiple enhancer-promoter, promoter
enhancer, and enhancer-enhancer interactions. However, neither short-term
activation of HIF by hypoxia, nor long-term stabilization of HIF in von Hippel
Lindau (VHL)-defective cells greatly alters these interactions, indicating that
at least under these conditions, HIF can operate on preexisting patterns of
chromatin-chromatin interactions that define potential transcriptional targets
and permit rapid gene activation by hypoxic stress.
PMID- 27506893
TI - Epigenetic suppression of potassium-chloride co-transporter 2 expression in
inflammatory pain induced by complete Freund's adjuvant (CFA).
AB - BACKGROUND: Multiple mechanisms contribute to the stimulus-evoked pain
hypersensitivity that may be experienced after peripheral inflammation.
Persistent pathological stimuli in many pain conditions affect the expression of
certain genes through epigenetic alternations. The main purpose of our study was
to investigate the role of epigenetic modification on potassium-chloride co
transporter 2 (KCC2) gene expression in the persistence of inflammatory pain.
METHODS: Persistent inflammatory pain was induced through the injection of
complete Freund's adjuvant (CFA) in the left hind paw of rats. Acetyl-histone H3
and H4 level was determined by chromatin immunoprecipitation in the spinal dorsal
horn. Pain behaviour and inhibitory synaptic function of spinal cord were
determined before and after CFA injection. KCC2 expression was determined by real
time RT-PCR and Western blot. Intrathecal KCC2 siRNA (2 MUg per 10 MUL per rat)
or HDAC inhibitor (10 MUg per 10 MUL per rat) was injected once daily for 3 days
before CFA injection. RESULTS: Persistent inflammatory pain epigenetically
suppressed KCC2 expression through histone deacetylase (HDAC)-mediated histone
hypoacetylation, resulting in decreased inhibitory signalling efficacy. KCC2
knock-down caused by intrathecal administration of KCC2 siRNA in naive rats
reduced KCC2 expression in the spinal cord, leading to sensitized pain behaviours
and impaired inhibitory synaptic transmission in their spinal cords. Moreover,
intrathecal HDAC inhibitor injection in CFA rats increased KCC2 expression,
partially restoring the spinal inhibitory synaptic transmission and relieving the
sensitized pain behaviour. CONCLUSION: These findings suggest that the
transcription of spinal KCC2 is regulated by histone acetylation epigenetically
following CFA. SIGNIFICANCE: Persistent pain suppresses KCC2 expression through
HDAC-mediated histone hypoacetylation and consequently impairs the inhibitory
function of inhibitory interneurons. Drugs such as HDAC inhibitors that suppress
the influences of persistent pain on the expression of KCC2 may serve as a novel
analgesic.
PMID- 27506894
TI - Gutmann's Donor Numbers Correctly Assess the Effect of the Solvent on the
Kinetics of SN Ar Reactions in Ionic Liquids.
AB - We report an experimental study on the effect of solvents on the model SN Ar
reaction between 1-chloro-2,4-dinitrobenzene and morpholine in a series of pure
ionic liquids (IL). A significant catalytic effect is observed with reference to
the same reaction run in water, acetonitrile, and other conventional solvents.
The series of IL considered include the anions, NTf2 (-) , DCN(-) , SCN(-) , CF3
SO3 (-) , PF6 (-) , and FAP(-) with the series of cations 1-butyl-3-methyl
imidazolium ([BMIM](+) ), 1-ethyl-3-methyl-imidazolium ([EMIM](+) ), 1-butyl-2,3
dimethyl-imidazolium ([BM2 IM](+) ), and 1-butyl-1-methyl-pyrrolidinium
([BMPyr](+) ). The observed solvent effects can be attributed to an "anion
effect". The anion effect appears related to the anion size (polarizability) and
their hydrogen-bonding (HB) abilities to the substrate. These results have been
confirmed by performing a comparison of the rate constants with Gutmann's
donicity numbers (DNs). The good correlation between rate constants and DN
emphasizes the major role of charge transfer from the anion to the substrate.
PMID- 27506895
TI - Relationships between intramuscular fat, muscle strength and gait independence in
older women: A cross-sectional study.
AB - AIM: The objectives of the present study were to examine the relationships
between intramuscular fat, muscle strength and gait independence, as well as to
clarify the intramuscular fat characteristics of dependent older women. METHODS:
A total of 25 older women who were unable to walk with or without assistance
(dependent group), 22 frail older women (frail group) and 22 healthy older women
(healthy group) participated in the present study. The frail participants could
walk independently, but showed three or more of the following characteristics:
slowness, weakness, weight loss, exhaustion and low physical activity. Outcome
measures were quadriceps intramuscular fat determined by ultrasound echo
intensity, and quadriceps muscle strength of the dependent, frail and healthy
groups. In addition, the degree of gait independence (functional independence
measures gait score) was assessed in the dependent and frail groups. RESULTS:
Echo intensity in the dependent group was significantly negatively correlated
with muscle strength and the functional independence measure gait score
(correlation coefficients -0.635 and -0.344, respectively). Furthermore, echo
intensity in the dependent group was significantly higher than in the healthy
group. There was no significant difference in echo intensity between the
dependent and frail groups. CONCLUSIONS: The present results suggest negative
relationships between intramuscular fat and muscle strength, and intramuscular
fat and degree of gait independence in dependent older women. In addition,
dependent older women have more intramuscular fat than healthy older women.
Geriatr Gerontol Int 2017; 17: 1683-1688.
PMID- 27506896
TI - The diversity of the human hair colour assessed by visual scales and instrumental
measurements. A worldwide survey.
AB - OBJECTIVES: To study (i) the diversity of the natural colour of the human hair
through both visual assessment of hair tone levels and colorimetric measurements
of hair strands collected from 2057 human male and female volunteers, from 23
regions of the world and (ii) the correlation between visual assessments and
colorimetric measurements. METHODS: Hair strands were analysed by a
spectrocolorimeter under the L*, a*, b* referential system and scored in vivo by
experts before sampling, through standardized visual reference scales based on a
1-10 range. RESULTS: Results show that from a typological aspect, black or dark
brown hairs largely predominate among studied ethnic groups, whereas Caucasian or
derived populations exhibit the widest palette of medium to fair shades, partly
explaining some past interbreeding among populations. Instrumental measurements
clearly confirm that a given colour of a pigmented hair, at the exclusion of red
hairs, is mostly governed by two components, L* and b*, from the L*, a*, b*
reference system. CONCLUSION: The comparisons between visual assessments and
instrumental data show that these appear closely linked. Darker hairs show close
or subtle variations in L*, a*, b* parameters, making their individual colour
differentiation calling for technical improvements in colorimetric measurements.
The latter are likely governed by other physical factors such as shape, diameter
and shine.
PMID- 27506897
TI - In reply: Monitoring recovery from neuromuscular block using acceleromyography at
the trapezius muscle: problems that must be considered.
PMID- 27506898
TI - A Combinatorial Investigation of the Response to Anti-angiogenic Therapy in
Breast Cancer: New Strategies for Patient Selection and Opportunities for
Reconsidering Anti-VEGF, Anti-PI3K and Checkpoint Inhibition.
PMID- 27506899
TI - Fetal programming of blood pressure in a transgenic mouse model of altered
intrauterine environment.
AB - KEY POINTS: Nitric oxide is essential in the vascular adaptation to pregnancy, as
knockout mice lacking nitric oxide synthase (NOS3) have abnormal utero-placental
perfusion, hypertension and growth restriction. We previously showed with ex vivo
studies on transgenic animals lacking NOS3 that adverse intrauterine environment
alters fetal programming of vascular reactivity in adult offspring. The current
research shows that altered vascular reactivity correlates with higher blood
pressure in vivo. Our data suggest that higher blood pressure depends on both
genetic background (NOS3 deficiency) and uterine environment, becomes more
evident with age (> 7 postnatal weeks), activity and stress, is gender specific
(preponderant among males), and can be affected by the sleep-awake cycle. In
utero or early postnatal life (< 7 weeks), before onset of hypertension, may
represent a potential window for intervention to prevent future cardiovascular
disorders. ABSTRACT: Nitric oxide is involved in the vascular adaptation to
pregnancy. Using transgenic animals, we previously showed that adverse
intrauterine environment alters vascular reactivity in adult offspring. The aim
of our study was to determine if altered vascular programming is associated with
abnormal blood pressure (BP) profiles in vivo. Mice lacking a functional
endothelial nitric oxide synthase (KO, NOS3-/- ) and wild-type mice (WT, NOS3+/+
) were crossbred to generate homozygous NOS3-/- (KO), maternally derived
heterozygous NOS3+/- (KOM: mother with adverse intrauterine environment from NOS3
deficiency), paternally derived heterozygous NOS3+/- (KOP: mother with normal in
utero milieu) and NOS3+/+ (WT) litters. BP was measured in vivo at 7, 14 and 21
weeks of age. After univariate analysis, multivariate population-averaged linear
regression models were used to identify factors affecting BP. When compared to WT
offspring, systolic (SBP), diastolic (DBP) and mean (MAP) BP progressively
increased from KOP, to KOM, and peaked among KO (P < 0.001), although
significance was not reached for KOP. Higher BP was also associated with male
gender, older age (> 7 postnatal weeks), higher locomotor activity, daytime
recordings, and recent blood pressure transducer insertion (P < 0.001). Post hoc
analysis showed that KOM had higher SBP than KOP (P < 0.05). Our study indicates
that adverse intrauterine environment contributes, along with multiple other
factors, to account for hypertension; moreover, in utero or early postnatal life
may represent a possible therapeutic window for prevention of cardiovascular
disease later in life.
PMID- 27506900
TI - INFORMEG, a new evaluation system for family medicine trainees: feasibility in an
Italian rural setting.
AB - INTRODUCTION: In Italy the course to become a general practitioner (GP) lasts 3
years and includes both theoretical and practical study. Different from the
theoretical part, until recently the practical activity has not been assessed at
all. The Emilia Romagna Regional Health Authority has developed a special program
called INFORMEG (Management of Tutoring during the Triennial Specific Training in
General Practice), aimed at assessing primary doctor trainees' practical skills.
INFORMEG includes a list of pre-defined cases of specific diseases, conditions or
health problem, a web application and a smartphone app, aimed at assisting
trainee self-management and helping the tutor in the assessment of trainee
performance. The Emilia Romagna Regional Health Authority divided the pre-defined
cases into three categories (A, B and C) according to their relevance to a
trainee's education and coded them using the International Classification of
Primary Care (ICPC). The aim of this project report is to illustrate the
implementation of INFORMEG in a rural setting. METHODS: Program evaluation took
place from 2 May to 31 October 2013 during GPs' routine clinical activities. The
following steps were accomplished during every meeting: (1) consultation
recording; (2) identification of the reason for the encounter (RfE); (3)
classification of the diagnostic procedure(s) performed
(diagnostic/therapeutic/test results/administrative/advice); (4) classification
of special procedures called 'practical clinical skills' and (5) elaboration of
the final diagnosis after the encounter. RESULTS: The number of cases of specific
disease or condition encountered by the trainee were 98 for type A, 57 for type B
and 22 for type C. A total of 605 RfEs were collected: 376 for type A cases, 147
for type B cases and 82 for type C cases. A total of 976 procedures were
performed during the 6 months: 590 procedures for the type A cases, 271 for type
B and 115 for type C. CONCLUSIONS: The pre-selected health problems were almost
all addressed, thus confirming the good degree of representativeness of these
clinical cases even in a rural setting. The ICPC coding helped the trainee in the
construction of the case according to the logical process of family medicine. Two
things to amend in INFORMEG are the absence of common arrhythmic conditions such
as atrial fibrillation and the absence of means to assess the patient-trainee
relationship.
PMID- 27506901
TI - Mangrovimonas xylaniphaga sp. nov. isolated from estuarine mangrove sediment of
Matang Mangrove Forest, Malaysia.
AB - A Gram-staining-negative, aerobic, rod-shaped, yellow-orange-pigmented, gliding
bacterium, designated as strain ST2L12T, was isolated from estuarine mangrove
sediment from Matang Mangrove Forest, Perak, Malaysia. Strain ST2L12T grew at 15
39 degrees C, pH 6-8 and in 1-6 % (w/v) NaCl. This strain was able to degrade
xylan and casein. 16S rRNA gene sequence analysis showed 95.3-92.8 % similarity
to members of the genera Mangrovimonas, Meridianimaribacter, Sediminibacter,
Gaetbulibacter and Hoppeia. Phylogenetic analysis indicated that it belonged to
the family Flavobacteriaceae. Respiratory quinone present was menaquinone-6 (MK
6), and the DNA G+C content was 38.3 mol%. The predominant fatty acids were iso
C15:0, iso-C15:1, C15:0 and iso-C17:0 3-OH. Moreover, previous genome comparison
study showed that the genome of ST2L12T is 1.4 times larger compared to its
closest relative, Mangrovimonas yunxiaonensis LYYY01T. Phenotypic, fatty acid,
16S rRNA gene sequence and previous genome data indicate that strain ST2L12T
represents a novel species of the genus Mangrovimonas in the family
Flavobacteriaceae, for which the name Mangrovimonas xylaniphaga sp. nov. is
proposed. The type strain of Mangrovimonas xylaniphaga is ST2L12T (=LMG
28914T=JCM 30880T).
PMID- 27506903
TI - Systematic Review of Randomized Controlled Trials of Endothelin Receptor
Antagonists for Pulmonary Arterial Hypertension.
AB - BACKGROUND: There are currently three Food and Drug Administration approved
endothelin receptor antagonists (ERAs): bosentan, ambrisentan, and macitentan.
There is a growing body of evidence that demonstrates the beneficial effects of
ERAs in patients with pulmonary arterial hypertension (PAH). OBJECTIVES: To
compare the available evidence from randomized clinical trials for specific
outcomes of different endothelin antagonists for the treatment of PAH. METHODS: A
multi-database search of randomized controlled trials up to March 15, 2016 was
conducted for those that would measure functional parameters of patients with PAH
treated with ERA monotherapy versus placebo. Studies that analyzed 6-min walking
distance, pulmonary vascular resistance, pulmonary arterial pressure, or WHO
functional status were incorporated for analysis. A total of 15 trials and 2
subanalyses were compiled and quality and abovementioned outcomes were compared
among studies. RESULTS: A constant decrease in pulmonary vascular resistance and
pulmonary arterial pressure was globally reported among the different studies,
resulting in increased 6-min walking distance and functional status compared to
placebo. CONCLUSIONS: Although this evidence clearly shows the benefit of ERAs,
studies, which compare ERAs against one another and with other therapies for
progressive PAH, have been lacking. Larger and longer studies are necessary to
define the role of ERAs as standalone agents and in combination therapies.
PMID- 27506902
TI - Respiratory Muscle Assessment in Acute Guillain-Barre Syndrome.
AB - PURPOSE: Guillain-Barre Syndrome (GBS) is a life-threatening disease due to
respiratory muscle involvement. This study aimed at objectively assessing the
course of respiratory muscle function in GBS subjects within the first week of
admission to an intensive care unit. METHODS: Medical Research Council Sum Score
(MRC-SS), vigorimetry, spirometry, and respiratory muscle function tests
(inspiratory/expiratory muscle strength: PImax/PEmax, sniff nasal pressure:
SnPna) were assessed twice daily. GBS Disability Score (GBS-DS) was assessed once
daily. On days one (d1) and seven (d7), blood gases and twitch mouth pressure
during magnetic phrenic nerve stimulation (Pmo,tw) were additionally evaluated.
RESULTS: Nine subjects were included. MRC-SS, vigorimetry, PImax, and SnPna
increased between d1 and d7. GBS-DS, spirometry and Pmo,tw remained unaltered.
Only SnPna correlated closely with the MRC-SS on both d1 (r = 0.77, p = 0.02) and
d7 (r = 0.74, p = 0.02). CONCLUSION: SnPna was the only parameter that correlated
with MRC-SS, while the current gold standard of spirometry measurement did not.
PMID- 27506904
TI - HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell
carcinoma.
AB - BACKGROUND: Class I histone deacetylases (HDACs) have been reported to be
overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression
of class II HDACs is unknown. METHODS: Four isogenic cell lines C2/C2VHL and 786
O/786-OVHL with differential VHL expression are used in our studies. Cobalt
chloride is used to mimic hypoxia in vitro. HIF-2alpha knockdowns in C2 and 786-O
cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion
and migration assays are used to investigate the role of HDAC 1 and HDAC 6
expression in ccRCC cells. Comparisons are made between experimental groups using
the paired T-test, the two-sample Student's T-test or one-way ANOVA, as
appropriate. ccRCC and the TCGA dataset are used to observe the clinical
correlation between HDAC 1 and HDAC 6 overexpression and overall and progression
free survival. RESULTS: Our analysis of tumor and matched non-tumor tissues from
radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only
in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression
increased cell invasion and motility, respectively, in ccRCC cells. HDAC1
regulated invasiveness by increasing matrix metalloproteinase (MMP) expression.
Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF
isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1
promoter along with chromatin immunoprecipitation data suggests that HIF-2alpha
is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen
receptor alpha (ERalpha) were co-localized in cytoplasm of ccRCC cells and HDAC6
enhanced cell motility by decreasing acetylated alpha-tubulin expression, and
this biological effect was attenuated by either biochemical or pharmacological
inhibition. Finally, analysis of human ccRCC specimens revealed positive
correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated
with worse overall survival in the TCGA dataset. CONCLUSIONS: Taking together,
these results suggest that HDAC1 and HDAC6 may play a role in ccRCC biology and
could represent rational therapeutic targets.
PMID- 27506905
TI - Full-length autonomous transposable elements are preferentially targeted by
expression-dependent forms of RNA-directed DNA methylation.
AB - BACKGROUND: Chromatin modifications such as DNA methylation are targeted to
transposable elements by small RNAs in a process termed RNA-directed DNA
methylation (RdDM). In plants, canonical RdDM functions through RNA polymerase IV
to reinforce pre-existing transposable element silencing. Recent investigations
have identified a "non-canonical" form of RdDM dependent on RNA polymerase II
expression to initiate and re-establish silencing of active transposable
elements. This expression-dependent RdDM mechanism functions through RNAi
degradation of transposable element mRNAs into small RNAs guided by the RNA
dependent RNA polymerase 6 (RDR6) protein and is therefore referred to as RDR6
RdDM. RESULTS: We performed whole-genome MethylC-seq in 20 mutants that
distinguish RdDM mechanisms when transposable elements are either
transcriptionally silent or active. We identified a new mechanism of expression
dependent RdDM, which functions through DICER-LIKE3 (DCL3) but bypasses the
requirement of both RNA polymerase IV and RDR6 (termed DCL3-RdDM). We found that
RNA polymerase II expression-dependent forms of RdDM function on over 20 % of
transcribed transposable elements, including the majority of full-length elements
with all of the domains required for autonomous transposition. Lastly, we find
that RDR6-RdDM preferentially targets long transposable elements due to the
specificity of primary small RNAs to cleave full-length mRNAs. CONCLUSIONS:
Expression-dependent forms of RdDM function to critically target DNA methylation
to full-length and transcriptionally active transposable elements, suggesting
that these pathways are key to suppressing mobilization. This targeting
specificity is initiated on the mRNA cleavage-level, yet manifested as chromatin
level silencing that in plants is epigenetically inherited from generation to
generation.
PMID- 27506906
TI - Quantitative [18F]FMISO PET Imaging Shows Reduction of Hypoxia Following
Trastuzumab in a Murine Model of HER2+ Breast Cancer.
AB - PURPOSE: Evaluation of [18F]fluoromisonidazole ([18F]FMISO)-positron emission
tomography (PET) imaging as a metric for evaluating early response to trastuzumab
therapy with histological validation in a murine model of HER2+ breast cancer.
PROCEDURES: Mice with BT474, HER2+ tumors, were imaged with [18F]FMISO-PET during
trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from
imaging. RESULTS: [18F]FMISO-PET indicated significant decreases in hypoxia
beginning on day 3 (P < 0.01) prior to changes in tumor size. These results were
confirmed with pimonidazole staining on day 7 (P < 0.01); additionally, there was
a significant positive linear correlation between histology and PET imaging (r 2
= 0.85). CONCLUSIONS: [18F]FMISO-PET is a clinically relevant modality which
provides the opportunity to (1) predict response to HER2+ therapy before changes
in tumor size and (2) identify decreases in hypoxia which has the potential to
guide subsequent therapy.
PMID- 27506908
TI - The role of web sharing, species recognition and host-plant defence in
interspecific competition between two herbivorous mite species.
AB - When competing with indigenous species, invasive species face a problem, because
they typically start with a few colonizers. Evidently, some species succeeded,
begging an answer to the question how they invade. Here, we investigate how the
invasive spider mite Tetranychus evansi interacts with the indigenous species T.
urticae when sharing the solanaceous host plant tomato: do they choose to live
together or to avoid each other's colonies? Both species spin protective, silken
webs on the leaf surfaces, under which they live in groups of con- and possibly
heterospecifics. In Spain, T. evansi invaded the non-crop field where native
Tetranychus species including T. urticae dominated. Moreover, T. evansi
outcompetes T. urticae when released together on a tomato plant. However,
molecular plant studies suggest that T. urticae benefits from the local down
regulation of tomato plant defences by T. evansi, whereas T. evansi suffers from
the induction of these defences by T. urticae. Therefore, we hypothesize that T.
evansi avoids leaves infested with T. urticae whereas T. urticae prefers leaves
infested by T. evansi. Using wild-type tomato and a mutant lacking jasmonate
mediated anti-herbivore defences, we tested the hypothesis and found that T.
evansi avoided sharing webs with T. urticae in favour of a web with conspecifics,
whereas T. urticae more frequently chose to share webs with T. evansi than with
conspecifics. Also, T. evansi shows higher aggregation on a tomato plant than T.
urticae, irrespective of whether the mites occur on the plant together or not.
PMID- 27506907
TI - High-throughput sequencing and degradome analysis reveal altered expression of
miRNAs and their targets in a male-sterile cybrid pummelo (Citrus grandis).
AB - BACKGROUND: G1 + HBP is a male sterile cybrid line with nuclear genome from
Hirado Buntan pummelo (C. grandis Osbeck) (HBP) and mitochondrial genome from
"Guoqing No.1" (G1, Satsuma mandarin), which provides a good opportunity to study
male sterility and nuclear-cytoplasmic cross talk in citrus. High-throughput sRNA
and degradome sequencing were applied to identify miRNAs and their targets in G1
+ HBP and its fertile type HBP during reproductive development. RESULTS: A total
of 184 known miRNAs, 22 novel miRNAs and 86 target genes were identified. Some of
the targets are transcription factors involved in floral development, such as
auxin response factors (ARFs), SQUAMOSA promoter binding protein box (SBP-box),
MYB, basic region-leucine zipper (bZIP), APETALA2 (AP2) and transport inhibitor
response 1 (TIR1). Eight target genes were confirmed to be sliced by
corresponding miRNAs using 5' RACE technology. Based on the sequencing abundance,
42 differentially expressed miRNAs between sterile line G1 + HBP and fertile line
HBP were identified. Differential expression of miRNAs and their target genes
between two lines was validated by quantitative RT-PCR, and reciprocal expression
patterns between some miRNAs and their targets were demonstrated. The regulatory
mechanism of miR167a was investigated by yeast one-hybrid and dual-luciferase
assays that one dehydrate responsive element binding (DREB) transcription factor
binds to miR167a promoter and transcriptionally repress miR167 expression.
CONCLUSION: Our study reveals the altered expression of miRNAs and their target
genes in a male sterile line of pummelo and highlights that miRNA regulatory
network may be involved in floral bud development and cytoplasmic male sterility
in citrus.
PMID- 27506909
TI - Expectations affect psychological and neurophysiological benefits even after a
single bout of exercise.
AB - The study investigated whether typical psychological, physiological, and
neurophysiological changes from a single exercise are affected by one's beliefs
and expectations. Seventy-six participants were randomly assigned to four groups
and saw different multimedia presentations suggesting that the subsequent
exercise (moderate 30 min cycling) would result in more or less health benefits
(induced expectations). Additionally, we assessed habitual expectations
reflecting previous experience and beliefs regarding exercise benefits.
Participants with more positive habitual expectations consistently demonstrated
both greater psychological benefits (more enjoyment, mood increase, and anxiety
reduction) and greater increase of alpha-2 power, assessed with
electroencephalography. Manipulating participants' expectations also resulted in
largely greater increases of alpha-2 power, but not in more psychological
exercise benefits. On the physiological level, participants decreased their blood
pressure after exercising, but this was independent of their expectations. These
results indicate that habitual expectations in particular affect exercise-induced
psychological and neurophysiological changes in a self-fulfilling manner.
PMID- 27506910
TI - Assessment of factors associated with the quality of life of patients living with
HIV/HCV co-infection.
AB - This study compared the quality of life (QoL) of HIV-infected patients with and
without hepatitis C and examined the sociodemographic, HIV-related and
psychological symptoms associated with the QoL domains in patients with HIV/HCV
co-infection. The sample consisted of 248 HIV/HCV co-infected patients (18-74
years, 81.5 % male) and 482 patients only with HIV (24-78 years, 62.7 % male).
Participants completed the WHOQOL-HIV-Bref questionnaire and the Brief Symptom
Inventory. The HIV/HCV co-infected patients reported significantly lower QoL in
all domains, as well as significantly lower scores in 10 of the 17 specific
facets. Overall, among the co-infected patients, male gender, employment,
combination antiretroviral therapy use and fewer depressive and anxiety symptoms
were significantly associated with higher QoL. Symptoms of psychological distress
accounted for significant variability in the QoL scores of co-infected patients.
These data reinforce the need for tailored interventions to improve the overall
well-being of HIV/HCV co-infected patients.
PMID- 27506912
TI - Binary and ternary recombination of H2D(+) and HD2(+) ions with electrons at 80
K.
AB - The recombination of deuterated trihydrogen cations with electrons has been
studied in afterglow plasmas containing mixtures of helium, argon, hydrogen and
deuterium. By monitoring the fractional abundances of H3(+), H2D(+), HD2(+) and
D3(+) as a function of the [D2]/[H2] ratio using infrared absorption observed in
a cavity ring down absorption spectrometer (CRDS), it was possible to deduce
effective recombination rate coefficients for H2D(+) and HD2(+) ions at a
temperature of 80 K. From pressure dependences of the measured effective
recombination rate coefficients the binary and the ternary recombination rate
coefficients for both ions have been determined. The inferred binary and ternary
recombination rate coefficients are: alphabinH2D(80 K) = (7.1 +/- 4.2) * 10(-8)
cm(3) s(-1), alphabinHD2(80 K) = (8.7 +/- 2.5) * 10(-8) cm(3) s(-1), KH2D(80 K) =
(1.1 +/- 0.6) * 10(-25) cm(6) s(-1) and KHD2(80 K) = (1.5 +/- 0.4) * 10(-25)
cm(6) s(-1).
PMID- 27506913
TI - [Kondylomer viste sig at vaere peniscancer].
PMID- 27506914
TI - [Multidisciplinary teams in cancer care].
AB - Multidisciplinary teams (MDTs) are considered a core component of cancer care
worldwide. It is commonly believed that MDTs ensure higher-quality decision
making and improved outcomes for the patients. However, the evidence underpinning
MDTs is weak and the degree to which they have been absorbed into clinical
practice varies widely. Based on a literature review this article explores
effects, barriers and potentials for improving MDTs in cancer care. A stronger
focus is needed on how MDTs can be optimized to achieve the best possible results
in cancer care.
PMID- 27506911
TI - Pain beliefs and problems in functioning among people with arthritis: a meta
analytic review.
AB - In this meta-analysis, we evaluated overall strengths of relation between beliefs
about pain, health, or illness and problems in functioning (i.e., functional
impairment, affective distress, pain severity) in osteoarthritis and rheumatoid
arthritis samples as well as moderators of these associations. In sum, 111
samples (N = 17,365 patients) met inclusion criteria. On average, highly
significant, medium effect sizes were observed for associations between beliefs
and problems in functioning but heterogeneity was also inflated. Effect sizes
were not affected by arthritis subtype, gender, or age. However, pain belief
content emerged as a significant moderator, with larger effect sizes for studies
in which personal incapacity or ineffectiveness in controlling pain was a content
theme of belief indices (i.e., pain catastrophizing, helplessness, self-efficacy)
compared to those examining locus of control and fear/threat/harm beliefs.
Furthermore, analyses of longitudinal study subsets supported the status of pain
beliefs risk factors for later problems in functioning in these groups.
PMID- 27506915
TI - [Individualized treatment of colon cancer].
AB - The treatment of colon cancer has undergone a rapid development with improved
surgical and medical regimes and the introduction of targeted treatments. This
review offers insight into the current available tailored treatment of colon
cancer, and some of the new tailored treatment possibilities with focus on
preoperative-, surgical- and post-operative treatment are presented.
PMID- 27506916
TI - [Systemic lupus erythematosus and pregnancy].
AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease which most
often affects women of childbearing age. Pregnancy is therefore an important
issue for the patient and the responsible physician. Pregnancy outcomes in women
with SLE has improved significantly over the latest decades, and current research
initiatives aim towards further improvement. Pregnant women with SLE are still
considered being at various levels of risk. In order to achieve the best possible
outcomes for mother and child, joint care in specialised multidisciplinary teams
including rheumatologists and obstetricians is recommended.
PMID- 27506917
TI - Overview of online two-dimensional liquid chromatography based on cell membrane
chromatography for screening target components from traditional Chinese
medicines.
AB - Cell membrane chromatography is a simple, specific, and time-saving technique for
studying drug-receptor interactions, screening of active components from complex
mixtures, and quality control of traditional Chinese medicines. However, the
short column life, low sensitivity, low column efficiency (so cannot resolve
satisfactorily mixture of compounds), low peak capacity, and inefficient in
structure identification were bottleneck in its application. Combinations of cell
membrane chromatography with multidimensional chromatography such as two
dimensional liquid chromatography and high sensitivity detectors like mass have
significantly reduced many of the above-mentioned shortcomings. This paper
provides an overview of the current advances in online two-dimensional-based cell
membrane chromatography for screening target components from traditional Chinese
medicines with particular emphasis on the instrumentation, preparation of cell
membrane stationary phase, advantages, and disadvantages compared to alternative
approaches. The last section of the review summarizes the applications of the
online two-dimensional high-performance liquid chromatography based cell membrane
chromatography reported since its emergence to date (2010-June 2016).
PMID- 27506918
TI - Clinical and non-clinical safety of artemisinin derivatives in pregnancy.
AB - Malaria in pregnancy is a clinically wasting infectious disease, where drug
therapy has to be promptly initiated. Currently, the treatment of this infection
depends on the use of artemisinin derivatives. The World Health Organization does
not recommend the use of these drugs in the first trimester of pregnancy due to
non-clinical findings that have shown embryolethality and teratogenic effects.
Nevertheless, until now, this toxicity has not been proved in humans. Artemisinin
derivatives mechanisms of embryotoxicity are related to depletion of circulating
embryonic primitive erythroblasts. Species differences in this sensitive period
for toxicity and the presence of malaria infection, which could reduce drug
distribution to the fetus, are significant to the risk assessment of artemisinin
derivatives treatment to pregnant women. In this review we aimed to assess the
results of non-clinical and clinical studies with artemisinin derivatives, their
mechanisms of embryotoxicity and discuss the safety of their use during
pregnancy.
PMID- 27506919
TI - 5-Position-selective C-H trifluoromethylation of 8-aminoquinoline derivatives.
AB - We developed a copper-catalyzed 5-position-selective C-H trifluoromethylation of
8-aminoquinoline derivatives. The reaction proceeded with high functional group
tolerance under mild conditions. In the case of quinolines with an amide,
carbamate, urea, or sulfonamide group at the 8-position of quinoline moieties, a
radical scavenger experiment indicated that the reaction proceeded via a radical
pathway. The protecting group of an 8-amidoquinoline derivative could be removed
by hydrolysis. On the other hand, the trifluoromethylation of 8-aminoquinolines
was also promoted by other Lewis acids as well as a copper catalyst and proceeded
even in the presence of a radical scavenger. These results indicated that the
trifluoromethylation of 8-aminoquinolines proceeded via a Friedel-Crafts-type
reaction. Interestingly, the copper salt works as either a catalyst for the
formation of a CF3 radical or a Lewis acid to promote a Friedel-Crafts-type
reaction, depending on the substrate.
PMID- 27506920
TI - A novel canine B-cell leukaemia cell line. Establishment, characterisation and
sensitivity to chemotherapeutics.
AB - We established a new B-cell leukaemia cell line CLB70 from a dog with chronic
lymphocytic leukaemia. This cell line is positive for CD20, CD45, CD79a, MHC
class II, IgG, IgM; weakly positive for CD21; and negative for CD3, CD4, CD5,
CD8, CD14, CD34, CD117. PCR for antigen receptor gene rearrangement (PARR)
analysis revealed a biclonal immunoglobulin heavy chain (IgH) gene rearrangement
and negative result for TCRgamma. Western blot analysis of anti- and pro
apoptotic proteins showed increased expression of Bcl-2, Mcl-1, NF-kB, and Ras,
and decreased expression of p53. CLB70 cells grow rapidly in vitro and are
tumourigenic in nude mice. The CLB70 line is highly sensitive to doxorubicin,
less sensitive to etoposide and imatinib, and resistant to piroxicam, celecoxib
and dexamethasone. Our results indicate that CLB70 cells are derived from mature
B-cells and they may be a useful tool for the development of new therapeutic
strategies for both dogs and humans.
PMID- 27506921
TI - Trusts spend 25 times more on locum fees than on recruiting for permanent posts.
PMID- 27506922
TI - Population levels of sport participation: implications for sport policy.
AB - BACKGROUND: Participation in sport can contribute to health-enhancing levels of
leisure-time physical activity. There are recent reports that participation in
sport in Australia is decreasing. However, these studies are limited to ages 15
years and over. METHODS: This study integrates sports club membership data from
five popular team sports and investigates sport participation across the lifespan
(4-100 years) by sex and region (metropolitan/non-metropolitan). RESULTS: Overall
participant numbers per annum increased from 414,167 in 2010 to 465,403 in 2012
corresponding to a rise in the proportion of Victorian's participating in these
sports from 7.5 % in 2010 to 8.3 % in 2012. The highest proportion of
participants was in the 10-14 year age range, with participation rates of 36 % in
2010 and 40 % in 2012. There was a considerably lower participation rate in the
15-19 year age group compared to the 10-14 age group, in all three years studied,
and the decline continued progressively with increasing age. Male and female age
profiles of participation were generally similar in shape, but the female peak at
age 10-14 was sharper than for the males, and conversely there were very few 4
year old female participants. Participation rates were generally higher in non
metropolitan than metropolitan areas; the difference increased with increasing
age from 4 to 34 years, then steadily declined, reaching parity at around 60
years of age. CONCLUSIONS: It is a positive sign that participation in these
popular sports increased by over 50,000 participants from 2010 to 2012. Large
proportions of the population aged 5-14 participate in club based sport.
Participation rates decline sharply in late adolescence, particularly for
females, and while this may not be a concern from a broad health perspective so
long as they transition into other forms of physical activity, it is certainly a
matter of concern for the sport sector. It is recommended that sport policy
places a higher priority on grass-roots participation and that sporting
organisations are supported to prioritise the retention issues occurring during
adolescence, particularly for females so as to maximise the potential for sport
to maintain its positive contribution to population wellbeing.
PMID- 27506923
TI - Improving access for community health and sub-acute outpatient services: protocol
for a stepped wedge cluster randomised controlled trial.
AB - BACKGROUND: Waiting lists for treatment are common in outpatient and community
services, Existing methods for managing access and triage to these services can
lead to inequities in service delivery, inefficiencies and divert resources from
frontline care. Evidence from two controlled studies indicates that an
alternative to the traditional "waitlist and triage" model known as STAT
(Specific Timely Appointments for Triage) may be successful in reducing waiting
times without adversely affecting other aspects of patient care. This trial aims
to test whether the model is cost effective in reducing waiting time across
multiple services, and to measure the impact on service provision, health-related
quality of life and patient satisfaction. METHODS/DESIGN: A stepped wedge cluster
randomised controlled trial has been designed to evaluate the impact of the STAT
model in 8 community health and outpatient services. The primary outcome will be
waiting time from referral to first appointment. Secondary outcomes will be
nature and quantity of service received (collected from all patients attending
the service during the study period and health-related quality of life (AQOL-8D),
patient satisfaction, health care utilisation and cost data (collected from a
subgroup of patients at initial assessment and after 12 weeks). Data will be
analysed with a multiple multi-level random-effects regression model that allows
for cluster effects. An economic evaluation will be undertaken alongside the
clinical trial. DISCUSSION: This paper outlines the study protocol for a fully
powered prospective stepped wedge cluster randomised controlled trial (SWCRCT) to
establish whether the STAT model of access and triage can reduce waiting times
applied across multiple settings, without increasing health service costs or
adversely impacting on other aspects of patient care. If successful, it will
provide evidence for the effectiveness of a practical model of access that can
substantially reduce waiting time for outpatient and community services with
subsequent benefits for both efficiency of health systems and patient care. TRIAL
REGISTRATION: Australian and New Zealand Clinical Trials Registry
ACTRN12615001016527 . Approved 15/9/2015.
PMID- 27506924
TI - Baicalein suppresses the proliferation of acute T-lymphoblastic leukemia Jurkat
cells by inhibiting the Wnt/beta-catenin signaling.
AB - Although the response rates of chemotherapy in patients with acute T
lymphoblastic leukemia (T-ALL) have improved significantly, the outcome of these
patients is still poor. Previous studies suggested that baicalein could inhibit
the growth of several cancers, while its effect on T-ALL cells remains unclear.
We used Jurkat cells as an in vitro model of T-ALL. Cell counting kit-8 assay and
cytometric analysis with Annexin V-FITC/PI double staining were used to
investigate the proliferation and apoptosis of Jurkat cells treated with
increasing concentration of baicalein for indicated time. RT-PCR and western
blotting was used to test the expression of Wnt/beta-catenin associated genes and
proteins. In cell viability assay, baicalein could inhibit the proliferation of
Jurkat cells both in dose- and time-dependent manners. In cell apoptosis assay,
baicalein could stimulate apoptosis of Jurkat cells both in dose- and time
dependent manners. Moreover, we demonstrated that baicalein could down-regulated
the mRNA and protein levels of beta-catenin and its widely accepted downstream
targets (c-Myc, cyclin D1, and Axin2) in dose-dependent manners. These results
proved that baicalein might be a potential choice for the treatment of T-ALL.
PMID- 27506925
TI - ?
PMID- 27506926
TI - Randomized Comparison of High-Sensitivity Troponin Reporting in Undifferentiated
Chest Pain Assessment.
AB - BACKGROUND: High-sensitivity troponin T (hs-TnT) assays promise greater
discrimination of evolving myocardial infarction, but the impact of unguided
implementation on the effectiveness of care is uncertain. METHODS AND RESULTS: We
evaluated the impact of hs-TnT reporting on care and outcome among chest pain
patients presenting to 5 emergency departments within a multicenter randomized
trial. Patients were allocated to hs-TnT reporting (hs-report) or standard
reporting (std-report; Roche Elecys). The primary end point was death and new or
recurrent acute coronary syndrome by 12 months. A total of 1937 patients without
ST-segment elevation were enrolled between July 2011 and March 2013. The median
age was 61 (interquartile range, 48-74) years, and 46.3% were women. During the
index hospitalization, 1466 patients (75.7%) had maximal troponin <30 ng/L within
24 hours. Randomization to hs-report format did not alter the admission rate (hs
report: 57.7% versus std-report: 58.0%; P=0.069). There was no difference in
angiography (hs-report: 11.9% versus std-report: 10.9%; P=0.479). The hs
reporting did not reduce 12-month death or new/recurrent acute coronary syndrome
in the overall population (hs-report: 9.7% versus std-report: 7.2% [hazard ratio,
0.83 (0.57-1.22); P=0.362]). However, among those with troponin levels <30 ng/L,
a modest reduction in the primary end point was observed (hs-report: 2.6% versus
std-report: 4.4%, [hazard ratio, 0.58; 95% confidence interval, 0.34-0.1.00;
P=0.050). CONCLUSIONS: High-sensitivity troponin reporting alone is associated
with only modest changes in practice. Clinical effectiveness in the adoption of
high-sensitivity troponin may require close coupling with protocols that guide
interpretation and care. CLINICAL TRIAL REGISTRATION: URL:
http://www.ANZCTR.org.au. Unique identifier: ACTRN12611000879965.
PMID- 27506927
TI - Nitrogen can improve the rapid response of photosynthesis to changing irradiance
in rice (Oryza sativa L.) plants.
AB - To identify the effect of nitrogen (N) nutrition on the dynamic photosynthesis of
rice plants, a pot experiment was conducted under two N conditions. The leaf N
and chlorophyll levels, as well as steady-state photosynthesis, were
significantly increased under high N. After the transition from saturating to low
light levels, decreases in the induction state (IS%) of leaf photosynthesis (A)
and stomatal conductance (gs) were more severe under low than under high N
supply. After the transition from low to flecked irradiance, the times to 90% of
maximum A (T90%A) were significantly longer under low than under high N supply.
Under flecked irradiance, the maximum A under saturating light (Amax-fleck) and
the steady-state A under low light (Amin-fleck) were both lower than those under
uniform irradiance (Asat and Ainitial). Under high N supply, Amax-fleck was
14.12% lower than Asat, while it was 22.80% lower under low N supply. The higher
IS%, shorter T90%A, and the lower depression of Amax-fleck from Asat under high N
supply led to a less carbon loss compared with under a low N supply. Therefore,
we concluded that N can improve the rapid response of photosynthesis to changing
irradiance.
PMID- 27506928
TI - The annual marine feeding aggregation of Atlantic sturgeon Acipenser oxyrinchus
in the inner Bay of Fundy: population characteristics and movement.
AB - Atlantic sturgeon Acipenser oxyrinchus aggregate to feed from May to October in
Minas Basin (45 degrees N; 64 degrees W), a large, cul-de-sac embayment of the
inner Bay of Fundy. The aggregation consists mainly of migrants from the Saint
John, NB and Kennebec Rivers, ME (99%). During 2004-2015, 4393 A. oxyrinchus were
taken as by-catch by commercial fish trawlers or at intertidal fishing weirs, and
1453 were marked and/or sampled and released. Fork length (LF ) ranged from 458
to 2670 mm, but 72.5% were <1500 mm. Mass (M) ranged from 0.5 to 58.0 kg. The
mass-length relationship for fish <=50 kg was log10 M = 3.32log10 LF - 5.71.
Observed growth of unsexed A. oxyrinchus recaptured after 1-8 years indicated
fish of 90-179 cm LF grew c. 2-4 cm a year. Ages obtained from pectoral spines
were from 4 to 54 years. The Von Bertalanffy growth model predicted K = 0.01 and
Linfinity = 5209 mm LF . Estimated annual mortality was 9.5-10.9%. Aggregation
sizes in 2008 and 2013 were 8804 and 9244 individuals, respectively. Fish
exhibited high fidelity for yearly return to Minas Basin and population estimates
indicated the total at-sea number utilizing the Basin increased from c. 10 700 in
2010 to c. 37 500 in 2015. Abundance in the Basin was greatest along the north
shore in spring and along the south shore in summer, suggesting clockwise
movement following the residual current structure. Marked individuals were
recaptured in other bays of the inner Bay of Fundy, north to Gaspe, Quebec, and
south to New Jersey, U.S.A., with 26 recoveries from the Saint John River, NB,
spawning run. Fish marked at other Canadian and U.S. sites were also recovered in
Minas Basin. Since all A. oxyrinchus migrate into and out of the Basin annually
they will be at risk of mortality if planned tidal power turbines are installed
in Minas Passage.
PMID- 27506929
TI - Novel educational interventions in residency increase knowledge of chronic liver
disease and career interest in hepatology.
AB - : There is an increasing burden of chronic liver disease (CLD) in the United
States but a significant shortage of hepatologists. Thus, it is necessary to
develop new recruitment strategies to the field of hepatology as well as ensure
that non-gastroenterology-trained physicians are able to capably assist in the
care of CLD. We established a novel, nonelective, inpatient hepatology rotation
that uses required modules in the American Association for the Study of Liver
Diseases Curriculum and Training-First Hepatitis B and C curriculums as well as
in LiverLearning. A paper-based anonymous assessment was distributed to the
inaugural 25 postgraduate years 2 and 3 internal medicine residents before and
after the 2-week rotation over the course of 1 year. Both the prerotation and
postrotation assessments included validated multiple-choice questions and Likert
type questions, which evaluated self-perceived knowledge and comfort with
managing CLD. The mean comfort level (1 = not at all comfortable/strongly
disagree, 5 = very comfortable/strongly agree) of managing several common liver
diseases increased significantly after completion of the rotation (i.e.,
cirrhosis 2.8 versus 3.8, P < 0.001; hepatitis B 2.4 versus 3.4, P = 0.001;
hepatitis C 2.6 versus 3.7, P = 0.002; nonalcoholic steatohepatitis 3.0 versus
4.0, P < 0.001; liver transplant care 2.1 versus 3.4, P < 0.001). There was also
a significantly increased interest in hepatology as a career (2.6 versus 3.0, P =
0.03). Finally, the mean percentage of multiple-choice questions answered
correctly on the pretest was 62% and posttest was 77% (P = 0.02). CONCLUSION: Our
novel curriculum and nonelective hepatology rotation has effectively demonstrated
improvement in internal medicine residents' comfort with and knowledge of CLD,
and increased career interest in hepatology was also observed after completion of
the curriculum, which suggests that more exposure to CLD could positively impact
recruitment to the workforce; larger, multicenter studies are needed to validate
these results. (Hepatology 2016;64:2210-2218).
PMID- 27506931
TI - Corrigendum: Conformational heterogeneity of the calmodulin binding interface.
PMID- 27506930
TI - Reduced interfacial recombination in dye-sensitized solar cells assisted with
NiO:Eu(3+),Tb(3+) coated TiO2 film.
AB - Eu(3+),Tb(3+) doped and undoped NiO films were deposited on TiO2 by a sol-gel
spin-coating method as the photoanodes of dye sensitized solar cells (DSSCs). A
comparative study with different structures including TiO2, TiO2/NiO and
TiO2/NiO:Eu(3+),Tb(3+) as the photoanodes was carried out to illustrate the
photovoltaic performance of solar cells. NiO could enhance the performance of
DSSCs ascribed to acting as a barrier for the charge recombination from the
fluorine doped tin oxide (FTO) to electrolyte and forming a p-n junction
(NiO/TiO2). Moreover, Eu(3+), Tb(3+) co-doped NiO could accelerate the electron
transfer at TiO2/dye/electrolyte interface, which further benefited the
performance of solar cells. The solar cells assembled with the photoelectrodes
consisting of NiO:Eu(3+),Tb(3+) and TiO2 exhibited short-circuit current density
(JSC) of 17.4 mA cm(-2), open-circuit voltage (VOC) of 780 mV and conversion
efficiency of 8.8%, which were higher than that with TiO2/NiO and pure TiO2. The
mechanisms of the influence of NiO and NiO:Eu(3+),Tb(3+) on the photovoltaic
performance of DSSCs were discussed.
PMID- 27506932
TI - Design and application of a target capture sequencing of exons and conserved non
coding sequences for the rat.
AB - BACKGROUND: Target capture sequencing is an efficient approach to directly
identify the causative mutations of genetic disorders. To apply this strategy to
laboratory rats exhibiting various phenotypes, we developed a novel target
capture probe set, TargetEC (target capture for exons and conserved non-coding
sequences), which can identify mutations not only in exonic regions but also in
conserved non-coding sequences and thus can detect regulatory mutations. RESULTS:
TargetEC covers 1,078,129 regions spanning 146.8 Mb of the genome. We applied
TargetEC to four inbred rat strains (WTC/Kyo, WTC-swh/Kyo, PVG/Seac, and
KFRS4/Kyo) maintained by the National BioResource Project for the Rat in Japan,
and successfully identified mutations associated with these phenotypes, including
one mutation detected in a conserved non-coding sequence. CONCLUSIONS: The method
developed in this study can be used to efficiently identify regulatory mutations,
which cannot be detected using conventional exome sequencing, and will help to
deepen our understanding of the relationships between regulatory mutations and
associated phenotypes.
PMID- 27506933
TI - NUMB negatively regulates the epithelial-mesenchymal transition of triple
negative breast cancer by antagonizing Notch signaling.
AB - Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with
higher rates of early relapse and metastasis, is frequently associated with
aberrant activation of epithelial-mesenchymal transition (EMT). Nonetheless, how
EMT is initiated and regulated during TNBC progression is not well understood.
Here, we report that NUMB is a negative regulator of EMT in both human mammary
epithelial cells and breast cancer cells. Reduced NUMB expression was
significantly associated with elevated EMT in TNBC. Conversely, overexpression of
NUMB strongly attenuated the EMT program and metastasis of TNBC cell lines.
Interestingly, we showed that NUMB employs different molecular mechanisms to
regulate EMT. In normal mammary epithelial cells and breast cancer cells
expressing wild-type p53, NUMB suppressed EMT by stabilizing p53. However, in
TNBC cells, loss of NUMB facilitated the EMT program by activating Notch
signaling. Consistent with these findings, low NUMB expression and high Notch
activity were significantly correlated with the TNBC subtype in patients.
Collectively, these findings reveal novel molecular mechanisms of NUMB in the
regulation of breast tumor EMT, especially in TNBC.
PMID- 27506934
TI - Acute myeloid leukemia stem cell markers in prognosis and targeted therapy:
potential impact of BMI-1, TIM-3 and CLL-1.
AB - Acute myeloid leukemia (AML) patients show high relapse rates and some develop
conventional chemotherapy resistance. Leukemia Stem Cells (LSCs) are the main
player for AML relapses and drug resistance. LSCs might rely on the B-cell
specific Moloney murine leukemia virus integration site-1 (BMI-1) in promoting
cellular proliferation and survival. Growth of LSCs in microenvironments that are
deprived of nutrients leads to up-regulation of the signaling pathways during the
progression of the disease, which may illustrate the sensitivity of LSCs to
inhibitors of those signaling pathways as compared to normal cells. We analyzed
the expression of LSC markers (CD34, CLL-1, TIM-3 and BMI-1) using quantitative
RT-PCR in bone marrow samples of 40 AML patients of different FAB types (M1, M2,
M3, M4, M5, and M7). We also studied the expression of these markers in 2 AML
cell lines (Kasumi-1 and KG-1a) using flow cytometry and quantitative RT-PCR. The
overexpression of TIM-3, CLL-1, and BMI-1 was markedly correlated with poor
prognosis in these patients. Our in vitro findings demonstrate that targeting BMI
1, which markedly increased in the leukemic cells, was associated with marked
decrease in leukemic burden. This study also presents results for blocking LSCs'
surface markers CD44, CLL-1, and TIM-3. These markers may play an important role
in elimination of AML. Our study indicates a correlation between the expression
of markers TIM-3, CLL-1, and especially of BMI-1 and the aggressiveness of AML
and thus the potential impact of prognosis and therapies that target LSCs on
improving the cure rates.
PMID- 27506935
TI - RWCFusion: identifying phenotype-specific cancer driver gene fusions based on
fusion pair random walk scoring method.
AB - While gene fusions have been increasingly detected by next-generation sequencing
(NGS) technologies based methods in human cancers, these methods have limitations
in identifying driver fusions. In addition, the existing methods to identify
driver gene fusions ignored the specificity among different cancers or only
considered their local rather than global topology features in networks. Here, we
proposed a novel network-based method, called RWCFusion, to identify phenotype
specific cancer driver gene fusions. To evaluate its performance, we used leave
one-out cross-validation in 35 cancers and achieved a high AUC value 0.925 for
overall cancers and an average 0.929 for signal cancer. Furthermore, we
classified 35 cancers into two classes: haematological and solid, of which the
haematological got a highly AUC which is up to 0.968. Finally, we applied
RWCFusion to breast cancer and found that top 13 gene fusions, such as BCAS3
BCAS4, NOTCH-NUP214, MED13-BCAS3 and CARM-SMARCA4, have been previously proved to
be drivers for breast cancer. Additionally, 8 among the top 10 of the remaining
candidate gene fusions, such as SULF2-ZNF217, MED1-ACSF2, and ACACA-STAC2, were
inferred to be potential driver gene fusions of breast cancer by us.
PMID- 27506936
TI - PTEN expression is a prognostic marker for patients with non-small cell lung
cancer: a systematic review and meta-analysis of the literature.
AB - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a known tumor
suppressor in non-small cell lung cancer (NSCLC). By performing a systematic
review and meta-analysis of the literature, we determined the prognostic value of
decreased PTEN expression in patients with NSCLC. We comprehensively and
systematically searched through multiple online databases up to May 22, 2016 for
NSCLC studies reporting on PTEN expression and patient survival outcome. Several
criteria, including the Newcastle-Ottawa Quality Assessment Scale (NOS), were
used to discriminate between studies. In total, 23 eligible studies with a total
of 2,505 NSCLC patients were included in our meta-analysis. Our results
demonstrated that decreased expression of PTEN correlated with poor overall
survival in NSCLC patients and was indicative of a poor prognosis for disease
free survival and progression-free survival in patients with NSCLC.
PMID- 27506937
TI - Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and
facilitates HPV-8- and UV-light induced skin carcinogenesis.
AB - Overexpression and increased activity of the small Rho GTPase Rac1 has been
linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted
deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes
reduced papilloma formation in a chemical skin carcinogenesis mouse model.
However, a potential role of Rac1 in HPV- and UV-light induced skin
carcinogenesis has not been investigated so far, solar UV radiation being an
important carcinogen to the skin.To investigate this, we deleted Rac1 or
modulated its activity in mice with transgenic expression of Human papilloma
virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or
deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with
a single dose, whereas constitutive activation of Rac1 strongly increases
papilloma frequency in these mice. Surprisingly, we observed that, upon chronic
UV-irradiation, the majority of mice with transgenic expression of HPV-8 and
epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken
together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its
activation is, on one hand, required for HPV-8- and UV-light induced papilloma
formation but, on the other, suppresses the development of squamous cell
carcinomas.
PMID- 27506938
TI - C23 promotes tumorigenesis via suppressing p53 activity.
AB - C23 is an abundant and multi-functional protein, which plays an important role in
various biological processes, including ribosome biogenesis and maturation, cell
cycle checkpoints and transcriptional regulation [1, 2]. However, the role of C23
in controlling tumorigenesis has not been well defined. Here we report that C23
is highly expressed in cancer cells and the elevated expression of C23
facilitates cancer cell proliferation in vitro and tumor xenograft growth in
vivo. Notably, C23 binds to p53 through its GAR domain and suppresses the
transcriptional activity of p53 under DNA damage and hypoxia. Moreover, the GAR
domain is critical for C23-mediated tumor cell proliferation both in vitro and in
vivo. Our findings reveal a novel role of C23 in tumorigenesis and suggest that
C23 may represent a potential therapeutic target for treating malignancy.
PMID- 27506939
TI - Inhibition of PlexA1-mediated brain tumor growth and tumor-associated
angiogenesis using a transmembrane domain targeting peptide.
AB - The neuropilin-plexin receptor complex regulates tumor cell migration and
proliferation and thus is an interesting therapeutic target. High expression of
neuropilin-1 is indeed associated with a bad prognosis in glioma patients. Q
RTPCR and tissue-array analyses showed here that Plexin-A1 is highly expressed in
glioblastoma and that the highest level of expression correlates with the worse
survival of patients. We next identified a developmental and tumor-associated pro
angiogenic role of Plexin-A1. Hence, by using molecular simulations and a two
hybrid like assay in parallel with biochemical and cellular assays we developed a
specific Plexin-A1 peptidic antagonist disrupting transmembrane domain-mediated
oligomerization of the receptor and subsequent signaling and functional activity.
We found that this peptide exhibits anti-tumor activity in vivo on different
human glioblastoma models including glioma cancer stem cells. Thus, screening
Plexin-A1 expression and targeting Plexin-A1 in glioblastoma patients exhibit
diagnostic and therapeutic value.
PMID- 27506940
TI - Aberrant DR5 transport through disruption of lysosomal function suggests a novel
mechanism for receptor activation.
AB - To examine reciprocal or unilateral implications between two cell destruction
processes, autophagy and apoptosis, in 5-Fluorouracil (5-FU)-treated tumor cells,
a combination of chemical inhibitors, RNAi and genetic approaches were used. In
contrast to cancer cells harboring obstructed apoptosis, either at the DISC or
the mitochondrial level, p53-deficiency generated signs of autophagy deregulation
upon chemotherapy. On the other, hand disruption of lysosomal function by
chloroquine, caused a profound decrease in apoptotic markers appearing in
response to 5-FU. DR5, which is essential for 5-FU-induced apoptosis, accumulated
in lysosomes and autophagosomes upon chloroquine treatment. Since neither 3-MA,
RNAi of critical autophagy regulators or inhibition of cathepsins reversed
apoptosis in a similar manner, it is likely that not autophagy per se but rather
correct receptor transport is an important factor for 5-FU cytotoxicity. We found
that apoptosis generated by TRAIL, the cognate ligand for DR5, remained unchanged
upon chloroquine lysosomal interference, indicating that 5-FU activates the
receptor by a discrete mechanism. In support, depletion of membrane cholesterol
or hampering cholesterol transport drastically reduced 5-FU cytotoxicity. We
conclude that targeting of lysosomes by chloroquine deregulates DR5 trafficking
and abrogates 5-FU- but not TRAIL-stimulated cell elimination, hence suggesting a
novel mechanism for receptor activation.
PMID- 27506941
TI - KDM4B plays an important role in mitochondrial apoptosis by upregulating HAX1
expression in colorectal cancer.
AB - Histone methyltransferases and demethylases regulate transcription by altering
the epigenetic marks on histones in tumorigenesis. Members of the histone
lysine(K)-specific demethylase 4 (KDM4) family are dysregulated in several types
of cancer. Here, we report a novel role for KDM4B in mitochondrial apoptosis. In
this study, we demonstrate that KDM4B is overexpressed in colorectal cancer (CRC)
tissues. Decreased expression of KDM4B significantly promoted apoptosis of CRC
cell lines. Moreover, our data indicate that HAX1 is required for KDM4B-mediated
mitochondrial apoptosis. The transcription of HAX1 was directly activated by
KDM4B. We also show that HAX1 is overexpressed in CRC tissues and is positively
correlated with KMD4B expression. Collectively, we demonstrate that KDM4B may
play an important role in mitochondrial apoptosis and represent a potential
therapeutic cancer target in CRC.
PMID- 27506942
TI - Prognostic nomogram for post-surgical treatment with adjuvant TACE in hepatitis B
virus-related hepatocellular carcinoma.
AB - OBJECTIVE: This study sought to establish an effective and reliable prognostic
nomogram to guide the decision for post-surgical adjuvant transarterial
chemoembolization (PA-TACE) in patients with hepatitis B virus-related (HBV)
hepatocellular carcinoma (HCC). RESULTS: The 1, 3, 5-year overall survival rates
were, respectively, 87.7%, 52.1% and 28.3% in the patients from the derivation
set and 91.7%, 57.1% and 34.1% in those from the validation set. Five risk
factors (HBV-DNA level, platelet count, vascular invasion, change of Child-Pugh
score, and tumor diameter) in the multivariate analysis were significantly
associated with prognosis. The statistical nomogram incorporated these five
factors achieved good calibration and discriminatory abilities with c-index of
0.75 (95% CI 0.67 to 0.83). The findings were supported by the independent
external validation set (c-index, 0.69; 95% CI 0.56 to 0.83). Patients who had a
nomogram score of less than 180 was considered to have higher survival benefit
from PA-TACE. METHODS: The nomogram was established based on data obtained from a
retrospective study on 235 consecutive patients with HBV HCC who received PA-TACE
as an initial therapy from 2006 to 2010 in our center. 84 patients who were
collected at another institution between 01/2008 and 12/2010 served as an
external validation set. The prognostic nomogram was developed based on the data
obtained before the PA-TACE procedure. Predictive accuracy and discriminative
ability of the nomogram were assessed by concordance index (C-index), calibration
curves, and validation set. CONCLUSIONS: The novel nomogram may achieve an
optimal prognostic prediction for PA-TACE in HBV-related HCC.
PMID- 27506945
TI - Sunitinib as salvage treatment including potent anti-tumor activity in
carcinomatous ulcers for patients with multidrug-resistant metastatic breast
cancer.
AB - OBJECTIVE: To evaluate the efficacy and safety of single-agent sunitinib as
salvage treatment in Chinese patients with multidrug-resistant metastatic breast
cancer (MBC). RESULTS: 37 patients were enrolled with median age of 48 years. 17
had hormone receptor (HR)-positive tumors, 7 had HER2-positive tumors, and 10 had
triple-negative tumors. Among 32 evaluable patients with follow-up, 6 (18.8%)
achieved partial response, 14 (43.8%) achieved stable disease, and 11 (34.4%)
exhibited tumor shrinkage. The response rate in 9 patients with carcinomatous
ulcers was 77.8%. The median progression free survival (PFS) was 8.6 weeks.
Patients with a better response had improved overall survival and PFS relative to
patients with a worse response (p = 0.007, p < 0.001). Compared with HR-negative
tumor, HR-positive tumor had significantly better response to sunitinib (p =
0.035). The most frequent non-hematologic adverse events were fatigue (82.8%) and
hypertension (34.5%). Grade 3/4 hematologic toxicity included neutropenia (82.8%)
and thrombocytopenia (79.3%). There was no correlation between the clinical
response and IHC findings. MATERIALS AND METHODS: Patients with MBC who were
resistant to multiple salvage regimens (>= 3 previous chemotherapy lines) were
enrolled to receive sunitinib monotherapy. Dosage adjustment was allowed
depending on adverse events. 14 patients underwent immunohistochemistry (IHC)
testing for VEGF, PDGFR, EGFR and c-KIT. CONCLUSIONS: Sunitinib salvage treatment
provided modest antitumor effect to patients with refractory multidrug-resistant
MBC, especially to those with troublesome carcinomatous ulcers. The treatment
related adverse events of sunitinib were manageable through dosage adjustment.
PMID- 27506944
TI - RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine
tumors.
AB - The factors triggering pancreatic neuroendocrine tumor (PanNET) progression are
largely unknown. Here we investigated the role and mechanisms of the sumoylation
enhancing protein RSUME in PanNET tumorigenesis. Immunohistochemical studies
showed that RSUME is strongly expressed in normal human pancreas, in particular
in beta-cells. RSUME expression is reduced in insulinomas and is nearly absent in
other types of PanNETs suggesting a role in PanNET tumorigenesis. In human
pancreatic neuroendocrine BON1 cells, RSUME stimulates hypoxia-inducible factor
1alpha (HIF-1alpha) and vascular endothelial growth factor-A (VEGF-A), which are
key components of tumor neovascularisation. In contrast, RSUME suppresses nuclear
factor-kappaB (NF-kappaB) and its target interleukin-8 (IL-8). Correspondingly,
PanNET cells with RSUME knockdown showed decreased HIF-1alpha activity and
increased NF-kappaB and IL-8 production leading to a moderate reduction of VEGF-A
release as reduced HIF-1alpha/VEGF-A production is partly compensated by NF
kappaB/IL-8-induced VEGF-A. Notably, RSUME stabilizes the tumor suppressor PTEN,
which is frequently lost in PanNETs and whose absence is associated with
metastasis formation. In vivo orthotopic transplantation of PanNET cells with or
without RSUME expression into nude mice showed that PanNETs without RSUME have
reduced PTEN expression, grow faster and form multiple liver metastases. In sum,
RSUME differentially regulates key components of PanNET formation suggesting that
the observed loss of RSUME in advanced PanNETs is critically involved in PanNET
tumorigenesis, particularly in metastasis formation.
PMID- 27506946
TI - A general strategy to optimize immunogenicity of HLA-B*0702 restricted cryptic
peptides from tumor associated antigens: Design of universal neo-antigen like
tumor vaccines for HLA-B*0702 positive patients.
AB - Tumor Associated Antigens (TAAs) are the privileged targets of almost all the
cancer vaccines tested to date. Unfortunately all these vaccines failed to show a
clinical efficacy. The main reason for this failure is the immune tolerance to
TAAs that are self-proteins expressed by normal and cancer cells. Self-tolerance
to TAAs is directed against their dominant rather than against their cryptic
epitopes. The best way to overcome self-tolerance to TAAs would therefore be to
target their cryptic epitopes. However, because of their low HLA-I affinity,
cryptic peptides are non-immunogenic and cannot be used to stimulate an antitumor
immune response unless their immunogenicity has been previously enhanced. In this
paper we describe a general approach to enhance immunogenicity of almost all the
HLA-B*0702 restricted cryptic peptides derived from TAAs. It consists in
substituting residues at position 1 or 9 of low HLA-B*0702 affinity cryptic
peptides by an Alanine or a Leucine respectively. These substitutions increase
affinity of peptides for HLA-B*0702. These optimized cryptic peptides are
strongly immunogenic and very importantly CTL they stimulate recognize their
native counterparts.TAAs derived optimized cryptic peptides can be considered as
universal antitumor vaccine since they escape self-tolerance, are immunogenic and
are not patient specific.
PMID- 27506948
TI - Acinetobacter spp. are associated with a higher mortality in intensive care
patients with bacteremia: a survival analysis.
AB - BACKGROUND: It has been challenging to determine the true clinical impact of
Acinetobacter spp., due to the predilection of this pathogen to colonize and
infect critically ill patients, who often have a poor prognosis. The aim of this
study was to assess whether Acinetobacter spp. bacteremia is associated with
lower survival compared with bacteremia caused by other pathogens in critically
ill patients. METHODS: This study was performed at Hospital das Clinicas,
University of Sao Paulo, Brazil. There are 12 intensive care units (ICUs) in the
hospital: five Internal Medicine ICUs (emergency, nephrology, infectious diseases
and respiratory critical care), three surgical ICU (for general surgery and liver
transplantion), an Emergency Department ICU for trauma patients, an ICU for
burned patients, a neurosurgical ICU and a post-operative ICU. A retrospective
review of medical records was conducted for all patients admitted to any of the
ICUs, who developed bacteremia from January 2010 through December 2011. Patients
with Acinetobacter spp. were compared with those with other pathogens (Klebsiella
pneumoniae, Staphylococcus aureus, Enterobacter spp., Enterococcus spp.,
Pseudomonas aeruginosa). We did a 30-day survival analysis. The Kaplan-Meier
method and log-rank test were used to determine the overall survival. Potential
prognostic factors were identified by bivariate and multivariate Cox regression
analysis. RESULTS: One hundred forty-one patients were evaluated. No differences
between patients with Acinetobacter spp. and other pathogens were observed with
regard to age, sex, APACHE II score, Charlson Comorbidity Score and type of
infection. Initial inappropriate antimicrobial treatment was more frequent in
Acinetobacter bacteremia (88 % vs 51 %). Bivariate analysis showed that age > 60
years, diabetes mellitus, and Acinetobacter spp. infection were significantly
associated with a poor prognosis. Multivariate model showed that Acinetobacter
spp. infection (HR = 1.93, 95 % CI: 1.25-2.97) and age > 60 years were
independent prognostic factors. CONCLUSION: Acinetobacter is associated with
lower survival compared with other pathogens in critically ill patients with
bacteremia, and is not merely a marker of disease severity.
PMID- 27506947
TI - G-protein-coupled receptors mediate omega-3 PUFAs-inhibited colorectal cancer by
activating the Hippo pathway.
AB - Colorectal cancer (CRC) is one of the most common cancers leading to high
mortality. However, long-term administration of anti-tumor therapy for CRC is not
feasible due to the side effects. Omega-3 polyunsaturated fatty acids (omega-3
PUFAs), particularly DHA and EPA, exert protection against CRC, but the
mechanisms are unclear. Here, we show that omega-3 PUFAs inhibit proliferation
and induce apoptosis of CRC cells in vitro and alleviate AOM/DSS-induced mice
colorectal cancer in vivo. Moreover, omega-3 PUFAs promote phosphorylation and
cytoplasmic retention of YAP and this effect was mediated by MST1/2 and LATS1,
suggesting that the canonical Hippo Pathway is involved in omega-3 PUFAs
function. We further confirmed that increase of pYAP by omega-3 PUFAs was
mediated by GPRs, including GPR40 and GPR120, which subsequently activate PKA via
Galphas, thus inducing the Hippo pathway activation. These data provide a novel
DHA/EPA-GPR40/120-Galphas-PKA-MST1/2-LATS1-YAP signaling pathway which is linked
to omega-3 PUFAs-induced inhibition of cell proliferation and promotion of
apoptosis in CRC cells, indicating a mechanism that could explain the anti-cancer
action of omega-3 PUFAs.
PMID- 27506949
TI - ETV6 rearrangement in a case of mammary analogue secretory carcinoma of the skin.
AB - Mammary analog secretory carcinoma of salivary glands is a relatively recently
recognized entity that harbors the ETV6-NTRK3 fusion transcript. To date, only
rare cases of mammary analog secretory carcinoma of the skin have been reported.
A 57-year-old man presented with a 6.0 cm cystic mass in the axilla, involving
the dermis and superficial subcutis. Microscopically, the tumor exhibited nodular
aggregation of tubular and microcystic structures embedded in the dense fibrotic
and hyalinized stroma. Characteristic 'colloid-like' eosinophilic secretory
material was present within intraluminal spaces. Tumor cells were largely
characterized by vesicular nuclei with inconspicuous nucleoli and pink vacuolated
cytoplasm. With respect to immunohistochemistry, tumor cells were intensely
positive for AE1/AE3, Cam 5.2, and CK7, whereas Ber-EP4 and CEA were completely
negative. A dual color break-apart fluorescence in situ hybridization probe
identified rearrangement of the ETV6 gene locus on chromosome 12. The patient is
alive with no evidence of recurrent disease or metastasis 3 years after the
initial surgery. In conclusion, we report a rare example of mammary analog
secretory carcinoma of the skin with ETV6 rearrangement. Awareness of this unique
cutaneous tumor and subsequent reporting of additional cases is necessary for
better characterization of its completely clinicopathologic spectrum.
PMID- 27506950
TI - Re: Alexander Kutikov, Marc C. Smaldone, Robert G. Uzzo, Miki Haifler, Gennady
Bratslavsky, Bradley C. Leibovich. Renal Mass Biopsy: Always, Sometimes, or
Never? Eur Urol 2016;70:403-6.
PMID- 27506951
TI - Medical Expulsive Therapy for Ureterolithiasis: The EAU Recommendations in 2016.
AB - Medical expulsive therapy (MET), in particular alpha-blockers, have been
recommended as supportive medication if observational treatment of a ureteral
stone was an option. Over the years, a considerable number of randomized
controlled trials (RCT) as well as several meta-analyses have been published on
MET, supporting the use of alpha-blockers. However, several recently published
high quality, large, placebo-controlled randomized trials raised serious doubts
about the effectiveness of alpha-blockers. The contradictory results of meta
analyses of small RCTs versus the findings of large, well conducted multicenter
trials show the methodological vulnerability of meta-analyses, in particular if
small single center, lower quality, papers have been included. Small single
center trials, for instance, tend to show larger treatment effects compared to
multicenter RCTs. It also shows the responsibility of careful planning when
conducting a RCT. Trial registration as a prerequisite for approval by ethics
committees could in addition minimize publication bias. Weighting the current
evidence on whether to use MET, or not, it seems that in distal ureteral stones
larger than 5mm, there may be a potential therapeutic benefit for the use of
alpha-blockers. Patients should be informed about the possible, but as yet
unproven benefit of using alpha-blockers in this situation, as well as their off
label use and potential side effects.
PMID- 27506952
TI - Fine mapping of a dominant gene conferring chlorophyll-deficiency in Brassica
napus.
AB - Leaf colour regulation is important in photosynthesis and dry material
production. Most of the reported chlorophyll-deficient loci are recessive. The
dominant locus is rarely reported, although it may be more important than the
recessive locus in the regulation of photosynthesis efficiency. During the
present study, we mapped a chlorophyll-deficient dominant locus (CDE1) from the
ethyl methanesulfonate-mutagenized Brassica napus line NJ7982. Using an F2
population derived from the chlorophyll-deficient mutant (cde1) and the canola
variety 'zhongshuang11', a high-density linkage map was constructed, consisting
of 19 linkage groups with 2,878 bins containing 13,347 SNP markers, with a total
linkage map length of 1,968.6 cM. Next, the CDE1 locus was mapped in a 0.9-cM
interval of chromosome C08 of B. napus, co-segregating with nine SNP markers. In
the following fine-mapping of the gene using the inherited F2:3 populations of
620 individuals, the locus was identified in an interval with a length of 311 kb.
A bioinformatics analysis revealed that the mapping interval contained 22 genes.
These results produced a good foundation for continued research on the dominant
locus involved in chlorophyll content regulation.
PMID- 27506953
TI - Influence of HLA-DR polymorphism and allergic sensitization on humoral immune
responses to intact pneumococcus in a transgenic mouse model.
AB - Asthma is independently associated with HLA-DR3 and increased risks of
pneumococcal diseases. We aimed to determine whether HLA-DR polymorphism (HLA
DRB1*03), sensitization to house dust mite (HDM), or their interaction affects
humoral immune responses to pneumococcal polysaccharide and protein antigens of
intact pneumococci. Induction of serum titers of anti-pneumococcal polysaccharide
and anti-surface protein IgM and IgG in response to immunization with intact
pneumococci (Pn) serotype 14 was determined using humanized HLA-DR3 and DR2
transgenic mice. Transgenic mice were sensitized by injecting HDM and challenged
with intranasal HDM. Mice were subsequently immunized with heat-killed Pn14 at
day 24. Serum titers of anti-phosphorylcholine (PC) IgM and IgG, anti
pneumococcal polysaccharide, capsular type 14 (PPS14) IgM and IgG, and anti
pneumococcal surface protein A (PspA) IgG were measured. We included a total of
44 mice (22 DR3 and 22 DR2 mice) and half of mice in each group were sensitized
with HDM (i.e. 22 HDM-sensitized and 22 control mice). HDM-sensitized mice,
irrespective of HLA-DR polymorphism, had significantly lower humoral immune
responses. HLA-DR3 mice, irrespective of HDM sensitization, elicited a
significantly lower anti-PC IgG response. In contrast, the anti-PspA IgG response
was higher in DR3 relative to DR2 mice. The effect of HDM sensitization on
lowering humoral immune responses to Pn14 was observed in DR3 mice regardless of
the nature of the antigen, whereas such decreases were observed only for the anti
PPS14 IgG and anti-PC IgM responses in DR2 mice. HDM sensitization lowered
humoral immune responses to intact pneumococcus and this effect was significantly
modified by the HLA-DR polymorphism.
PMID- 27506954
TI - Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum
Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed
Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group
Perspective of a NICE Single Technology Appraisal.
AB - As part of its Single Technology Appraisal process, the National Institute for
Health and Care Excellence (NICE) invited the manufacturer of olaparib
(AstraZeneca) to submit evidence on the clinical and cost effectiveness of
olaparib for the maintenance treatment of BRCA1/2 mutated (BRCAm), platinum
sensitive relapsed (PSR) ovarian, fallopian tube and peritoneal cancer in people
whose relapsed disease has responded to platinum-based chemotherapy. The Evidence
Review Group (ERG) produced a critical review of the evidence contained within
the company's submission (CS) to NICE. The clinical evidence related to one phase
II, double-blind randomised controlled trial that recruited 265 patients with PSR
serous ovarian cancer (OC) regardless of BRCAm status. Patients received olaparib
400 mg twice daily (b.i.d.) or matched placebo. In the whole population, the
primary endpoint of progression-free survival (PFS) was met (hazard ratio [HR]
0.35; 95 % confidence interval [CI] 0.25-0.49, p < 0.01) for olaparib versus
placebo. The BRCAm subgroup analysis (added after the study commenced but 1 month
before the primary analysis was undertaken) reported an HR for PFS of 0.18 (95 %
CI 0.10-0.31, p < 0.0001) for olaparib versus placebo, though interaction tests
appeared inconclusive. Overall survival was not statistically significant in the
whole group (HR 0.88; 95 % CI 0.64-1.21; p = 0.44) or the BRCAm subgroup (0.73;
95 % CI 0.45-1.17; p = 0.19), though treatment switching may have confounded
results. The exclusion of data from sites allowing crossover resulted in an HR
for overall survival (OS) of 0.52 (95 % CI 0.28-0.97, p = 0.039) in the BRCAm
group. Health-related quality-of-life measures were not significantly different
between groups. All post hoc exploratory outcomes (time to treatment
discontinuation/death, time to first subsequent therapy/death, and time to second
subsequent therapy/death) were statistically significantly better in the olaparib
arm in the whole population and the BRCAm subgroup analyses. Adverse events were
more frequent for olaparib but were largely minor or manageable. The company's
semi-Markov model assessed the cost effectiveness of olaparib versus routine
surveillance in patients with BRCAm PSR OC from a National Health Service (NHS)
and Personal Social Services (PSS) perspective over a lifetime horizon. The model
suggests that the incremental cost-effectiveness ratio (ICER) for olaparib versus
routine surveillance is expected to be approximately L49,146 per quality-adjusted
life-year (QALY) gained. The ERG did not consider the company's cost
effectiveness estimates to be credible. Additional ERG analyses suggested that
the ICER is likely to be more than L92,214 per QALY gained. Additional analyses
provided by the company in patients who received three or more lines of
chemotherapy suggested a more favourable cost-effectiveness profile for olaparib.
The NICE Appraisal Committee recommended olaparib for this subgroup provided the
cost of olaparib for people who continue to receive treatment after 15 months
will be met by the company.
PMID- 27506956
TI - Letter to the Editor.
PMID- 27506955
TI - Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror
pain.
AB - "Mirror pain" or mirror-image pain (MP) is pain opposite to the side of injury.
Mechanism and frequency in humans are not known. There is no consent on therapy.
Here we report that unilaterally injected botulinum toxin type A (BT-A) has
bilateral effect in experimental MP, thus deserves to be investigated as therapy
for this condition. We examined the localization of BT-A's bilateral
antinociceptive action in MP induced by 3 % carrageenan intramuscular injection
in Wistar rats. BT-A was applied peripherally (5 U/kg), into ipsilateral or
contralateral hind paw pad (i.pl.) and centrally (1 U/kg), at spinal
(intrathecally, i.t.) or supraspinal (intracisternally, i.c.) level.
Additionally, we examined the involvement of central opioid and GABAergic
systems, as well as the contribution of peripheral capsaicin-sensitive neurons to
BT-A's bilateral antinociceptive effect. Ipsilateral i.pl. and i.t. BT-A reduced
the bilateral mechanical sensitivity to von Frey filaments, while contralateral
i.pl. and i.c. treatments had no effect on either tested side. Bilateral
antinociceptive effect of ipsilateral i.pl. BT-A was prevented by MU-opioid
antagonist naloxonazine (1.5 MUg/10 MUl) and GABAA antagonist bicuculline (1
MUg/10 MUl) if applied at the spinal level, in contrast to supraspinal
application of the same doses. Local treatment of sciatic nerve with 2 %
capsaicin 5 days following BT-A i.pl. injection caused desensitization of sciatic
capsaicin-sensitive fibers, but did not affect bilateral antinociceptive effect
of BT-A and the presence of cleaved SNAP-25 at the spinal cord slices. Present
experiments suggest segmental actions of peripheral BT-A at spinal level, which
are probably not solely dependent on capsaicin-sensitive neurons.
PMID- 27506957
TI - Correlations of Promoter Methylation in WIF-1, RASSF1A, and CDH13 Genes with the
Risk and Prognosis of Esophageal Cancer.
AB - BACKGROUND This study was designed to explore the correlations of promoter
methylation in Wnt inhibitory factor-1 (WIF-1), ras-association domain family
member 1A (RASSF1A), and Cadherin 13 (CDH13) genes with the risk and prognosis of
esophageal cancer (EC). MATERIAL AND METHODS A total of 71 EC tissues from
resection and 35 adjacent normal tissues were collected. Methylation status in
the promoter region was detected by methylation- and non-methylation-specific
primers. Corresponding mRNA levels were detected by reverse transcriptase
polymerase chain reaction (RT-PCR). Correlations between the methylations of
these 3 genes and clinicopathologic characteristics were analyzed. Kaplan-Meier
method and Cox regression model were used to investigate the relationships
between WIF-1, RASSF1A, and CDH13 promoter methylations and the prognosis of EC.
RESULTS Compared with adjacent normal tissues, the methylation frequencies of WIF
1, RASSF1A, and CDH13 genes were significantly higher but the mRNA levels of
these 3 genes were significantly lower in EC tissues (all P<0.05). WIF-1 and
CDH13 promoter methylations were associated with the degree of tumor
differentiation and WIF-1 and RASSF1A promoter methylations were associated with
age (all P<0.05). The survival rates of patients with WIF-1, RASSF1A, and CDH13
methylations were significantly lower than those of patients without methylation
(all P<0.05). WIF-1, RASSF1A, and CDH13 promoter methylations were independent
risk factors affecting the prognosis of EC (all P<0.05). CONCLUSIONS WIF-1,
RASSF1A, and CDH13 promoter methylations are associated with EC. The methylation
levels are negatively related with the prognosis in EC.
PMID- 27506958
TI - Barren-ground caribou (Rangifer tarandus groenlandicus) behaviour after recent
fire events; integrating caribou telemetry data with Landsat fire detection
techniques.
AB - Fire regimes are changing throughout the North American boreal forest in complex
ways. Fire is also a major factor governing access to high-quality forage such as
terricholous lichens for barren-ground caribou (Rangifer tarandus groenlandicus).
Additionally, fire alters forest structure which can affect barren-ground
caribou's ability to navigate in a landscape. Here, we characterize how the size
and severity of fires are changing across five barren-ground caribou herd ranges
in the Northwest Territories and Nunavut, Canada. Additionally, we demonstrate
how time since fire, fire severity, and season result in complex changes in
caribou behavioural metrics estimated using telemetry data. Fire disturbances
were identified using novel gap-free Landsat surface reflectance composites from
1985 to 2011 across all herd ranges. Burn severity was estimated using the
differenced normalized burn ratio. Annual area burned and burn severity were
assessed through time for each herd and related to two behavioural metrics:
velocity and relative turning angle. Neither annual area burned nor burn severity
displayed any temporal trend within the study period. However, certain herds,
such as the Ahiak/Beverly, have more exposure to fire than other herds (i.e. Cape
Bathurst had a maximum forested area burned of less than 4 km2 ). Time since fire
and burn severity both significantly affected velocity and relative turning
angles. During fall, winter, and spring, fire virtually eliminated foraging
focused behaviour for all 26 years of analysis while more severe fires resulted
in a marked increase in movement-focused behaviour compared to unburnt patches.
Between seasons, caribou used burned areas as early as 1-year postfire,
demonstrating complex, nonlinear reactions to time since fire, fire severity, and
season. In all cases, increases in movement-focused behaviour were detected
postfire. We conclude that changes in caribou behaviour immediately postfire are
primarily driven by changes in forest structure rather than changes in
terricholous lichen availability.
PMID- 27506959
TI - A regioselective double Stille coupling reaction of bicyclic stannolanes.
AB - A regioselective double Stille coupling reaction was explored using bicyclic
stannolanes that were easily prepared from the radical cascade reaction of beta
amino-alpha-methylene esters. Various 1-bromo-2-iodoarenes underwent the double
coupling reaction to afford benzoisoindole derivatives in a regioselective
manner, where the carbon attached to the iodine selectively coupled with the
vinylic carbon, and then the carbon attached to bromine coupled with the alkyl
carbon. The combination of intra- and intermolecular coupling reactions provided
hexahydroindeno[1,2-b]pyrrole derivatives in good yields. The yields were further
improved in the presence of excess amounts of CsF. An attempt to identify the
reaction intermediate was made wherein the decomposition of the stannolanes with
aqueous HCl and HBr afforded trigonal bipyramidal (TBP) pentacoordinated tin
complexes, as confirmed by microanalyses and (119)Sn NMR. Using DCl for the
decomposition selectively introduced a deuterium to the E-position of the
exomethylene unit. The complexes smoothly underwent the intramolecular Stille
coupling reaction in the presence of both a palladium catalyst and DABCO,
affording hexahydroindeno[1,2-b]pyrroles in good yields. These results suggest
that the double coupling reaction progresses through a TBP tin complex, promoting
the second intramolecular coupling reaction between the aryl halide and Csp(3)
tin bond.
PMID- 27506960
TI - Wide dynamic range of surface-plasmon-resonance-based assay for hepatitis B
surface antigen antibody optimal detection in comparison with ELISA.
AB - Limit of detection (LOD), limit of quantification, and the dynamic range of
detection of hepatitis B surface antigen antibody (anti-HBs) using a surface
plasmon resonance (SPR) chip-based approach with Pichia pastoris-derived
recombinant hepatitis B surface antigen (HBsAg) as recognition element were
established through the scouting for optimal conditions for the improvement of
immobilization efficiency and in the use of optimal regeneration buffer.
Recombinant HBsAg was immobilized onto the sensor surface of a CM5 chip at a
concentration of 150 mg/L in sodium acetate buffer at pH 4 with added 0.6% Triton
X-100. A regeneration solution of 20 mM HCl was optimally found to effectively
unbind analytes from the ligand, thus allowing for multiple screening cycles. A
dynamic range of detection of ~0.00098-0.25 mg/L was obtained, and a sevenfold
higher LOD, as well as a twofold increase in coefficient of variance of the
replicated results, was shown as compared with enzyme-linked immunosorbent assay
(ELISA). Evaluation of the assay for specificity showed no cross-reactivity with
other antibodies tested. The ability of SPR chip-based assay and ELISA to detect
anti-HBs in human serum was comparable, indicating that the SPR chip-based assay
with its multiple screening capacity has greater advantage over ELISA.
PMID- 27506961
TI - An altered gut microbiota may trigger autoimmune-mediated acquired bone marrow
failure syndromes.
PMID- 27506962
TI - Laboratory testing for the diagnosis, evaluation, and management of systemic
lupus erythematosus: Still more questions for the next generations: A Tribute and
Thanks and in Memory of my mentor: Henry G. Kunkel.
AB - This paper is a review, personal memoir, a tribute to Henry Kunkel, and a
critique regarding laboratory tests used for the evaluation, diagnosis, and
understanding Autoimmune Rheumatic Diseases, in particular systemic lupus
erythematosus (SLE).
PMID- 27506964
TI - A Quick-responsive DNA Nanotechnology Device for Bio-molecular Homeostasis
Regulation.
AB - Physiological processes such as metabolism, cell apoptosis and immune responses,
must be strictly regulated to maintain their homeostasis and achieve their normal
physiological functions. The speed with which bio-molecular homeostatic
regulation occurs directly determines the ability of an organism to adapt to
conditional changes. To produce a quick-responsive regulatory system that can be
easily utilized for various types of homeostasis, a device called nano-fingers
that facilitates the regulation of physiological processes was constructed using
DNA origami nanotechnology. This nano-fingers device functioned in linked open
and closed phases using two types of DNA tweezers, which were covalently coupled
with aptamers that captured specific molecules when the tweezer arms were
sufficiently close. Via this specific interaction mechanism, certain
physiological processes could be simultaneously regulated from two directions by
capturing one biofactor and releasing the other to enhance the regulatory
capacity of the device. To validate the universal application of this device,
regulation of the homeostasis of the blood coagulant thrombin was attempted using
the nano-fingers device. It was successfully demonstrated that this nano-fingers
device achieved coagulation buffering upon the input of fuel DNA. This nano
device could also be utilized to regulate the homeostasis of other types of bio
molecules.
PMID- 27506965
TI - AdoMet analog synthesis and utilization: current state of the art.
AB - S-Adenosyl-l-methionine (AdoMet) is an essential enzyme cosubstrate in
fundamental biology with an expanding range of biocatalytic and therapeutic
applications. In recent years, technologies enabling the synthesis and
utilization of novel functional AdoMet surrogates have rapidly advanced.
Developments highlighted within this brief review include improved syntheses of
AdoMet analogs, unique S-adenosyl-l-methionine isosteres with enhanced stability,
and corresponding applications in epigenetics, proteomics and natural
product/small molecule diversification ('alkylrandomization').
PMID- 27506966
TI - Microstructural, mechanical, and histological evaluation of modified alginate
based scaffolds.
AB - Scaffolds are three-dimensional structures used for tissue regeneration being the
base in tissue engineering. These scaffolds are obtained from natural and/or
synthetic polymers and they should satisfy some specific requirements such as
biocompatibility, suitable mechanical, and microstructural properties to favor
cellular adhesion and neovascularization. This work shows a preclinic study about
the production of low and medium molecular weight alginate through the use of
calcium salts (calcium glutamate). The results showed prove that better
structures, distribution, and pore sizes as well as better mechanical properties
correspond to medium molecular weight alginate and higher calcium salts
concentration. This type of scaffold, after muscular cells cultivation, has been
proved as an excellent material for muscle growth. The histopathological analysis
shows a low inflammatory response, without a foreign body reaction, suitable
neovascularization and good fibroblasts incorporation. (c) 2016 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3107-3114, 2016.
PMID- 27506967
TI - Clinical Faceoff: Slightly Displaced, Isolated, Partial Articular Fracture of the
Radial Head.
PMID- 27506968
TI - CORR Insights(r): What Factors are Predictive of Patient-reported Outcomes? A
Prospective Study of 337 Shoulder Arthroplasties.
PMID- 27506969
TI - Cochrane in CORR (r): Surgical Versus Non-surgical Interventions for Treating
Patellar Dislocation (Review).
PMID- 27506970
TI - T1rho Hip Cartilage Mapping in Assessing Patients With Cam Morphology: How Can We
Optimize the Regions of Interest?
AB - BACKGROUND: T1rho MRI has been shown feasible to detect the biochemical status of
hip cartilage, but various region-of-interest strategies have been used,
compromising the reproducibility and comparability between different institutions
and studies. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine
representative regions of interest (ROIs) for cartilage T1rho mapping in hips
with a cam deformity; and (2) to assess intra- and interobserver reliability for
cartilage T1rho mapping in hips with a cam deformity. METHODS: The local ethics
committee approved this prospective study with written informed consent obtained.
Between 2010 and 2013, in 54 hips (54 patients), T1rho 1.5-T MRI was performed.
Thirty-eight hips (38 patients; 89% male) with an average age of 35 +/- 7.5 years
(range, 23-51 tears) were diagnosed with a cam deformity; 16 hips (16 patients;
87% male) with an average age of 34 +/- 7 years (range, 23-47 years) were
included in the control group. Of the 38 patients with a cam deformity, 20 were
pain-free and 18 symptomatic patients underwent surgery after 6 months of failed
nonsurgical management of antiinflammatories and physical therapy. Exclusion
criteria were radiologic sings of osteoarthritis with Tonnis Grade 2 or higher as
well as previous hip surgery. Three region-of-interest (ROI) selections were
analyzed: Method 1: as a whole; Method 2: as 36 to 54 small ROIs (sections of 30
degrees in the sagittal plane and 3 mm in the transverse plane); Method 3a: as
six ROIs (sections of 90 degrees in the sagittal plane and one-third of the
acetabular depth in the transverse plane: the anterosuperior and posterosuperior
quadrants, divided into lateral, intermediate, and medial thirds); and Method 3b:
as the ratio (anterosuperior over posterosuperior quadrant). ROIs in Method 3
represent the region of macroscopic cartilage damage, described in intraoperative
findings. To asses interobserver reliability, 10 patients were analyzed by two
observers (HA, GM). For intraobserver reliability, 20 hip MRIs were analyzed
twice by one observer (HA). To assess interscan reliability, three patients
underwent two scans within a time period of 2 weeks and were analyzed twice by
one observer (HA). T1rho values were compared using Student's t test. Interclass
correlation coefficient (ICC) and root mean square coefficient of variation (RMS
CV) were used to analyze intraobserver, interobserver, and interscan reliability.
RESULTS: Patients with a cam deformity showed increased T1rho values in the whole
hip cartilage (mean: 34.0 +/- 3.8 ms versus 31.4 +/- 3.0 ms; mean difference:
2.5; 95% confidence interval [CI], 4.7-0.4; p = 0.019; Method 1), mainly
anterolateral (2), in the lateral and medial thirds of the anterosuperior
quadrant (mean: 32.3 +/- 4.9 ms versus 29.4 +/- 4.1 ms; mean difference: 3.0; 95%
CI, 5.8-0.2; p = 0.039 and mean 36.5 +/- 5.6 ms versus 32.6 +/- 3.8 ms; mean
difference: 3.8; 95% CI, 6.9-0.8; p = 0.014), and in the medial third of the
posterosuperior quadrant (mean: 34.4 +/- 5.5 ms versus 31.1 +/- 3.9 ms; mean
difference: 3.1; 95% CI, 6.2-0.1; p = 0.039) (3a). The ratio was increased in the
lateral third (mean: 1.00 +/- 0.12 versus 0.90 +/- 0.15; mean difference: 0.10;
95% CI, 0.18-0.2; p = 0.018) (3b). ICC and RMS-CV were 0.965 and 4%
(intraobserver), 0.953 and 4% (interobserver), and 0.988 (all p < 0.001) and 9%
(inter-MR scan), respectively. CONCLUSIONS: Cartilage T1rho MRI mapping in hips
is feasible at 1.5 T with strong inter-, intraobserver, and inter-MR scan
reliability. The six ROIs (Method 3) showed a difference of T1rho values
anterolateral quadrant, consistent with the dominant area of cartilage injury in
cam femoroacetabular impingement, and antero- and posteromedial, indicating
involvement of the entire hip cartilage health. The six ROIs (Method 3) have been
shown feasible to assess cartilage damage in hips with a cam deformity using
T1rho MRI. We suggest applying this ROI selection for further studies using
quantitative MRI for assessment of cartilage damage in hips with a cam deformity
to achieve better comparability and reproducibility between different studies.
The application of this ROI selection on hips with other deformities (eg, pincer
deformity, developmental dysplasia of the hip, and acetabular retroversion) has
to be analyzed and potentially adapted. LEVEL OF EVIDENCE: Level III, diagnostic
study.
PMID- 27506971
TI - Is Botulinum Toxin Type A a Valuable Adjunct During Femoral Lengthening? A
Randomized Trial.
AB - BACKGROUND: Reduced joint ROM and distraction-induced pain are common complaints
of patients who have undergone gradual femoral lengthening. Attempts to reduce
the effects of lengthening on joint motion have included the use of botulinum
toxin to reduce the muscle forces that restrict motion. The benefits of this
approach during femoral lengthening, however, have not been conclusively
established. QUESTIONS/PURPOSES: We wished to evaluate the effects of botulinum
toxin type A (BtX-A) injection in the anterior thigh muscles during femoral
distraction osteogenesis on adjacent joint ROM and distraction-induced pain. We
asked: (1) Does injection of BtX-A in the quadriceps muscles lead to improved
knee and hip motion during femoral lengthening? (2) Does injection of BtX-A
reduce pain during femoral lengthening? METHODS: A single-center, double-blind,
randomized placebo-controlled trial was conducted. Forty-four patients (88
femurs) undergoing bilateral femoral lengthening for familial short stature were
included in the study. BtX-A (200 IU) was injected intraoperatively in the
quadriceps muscles of one thigh. An equal volume of sterile normal saline was
injected in the other thigh as a control. Selection of the limb receiving the
toxin was randomized. Clinical evaluation included a VAS score for pain
measurement, ROM evaluation of the hips and knees, and measurement of thigh
circumference. Side-to-side differences were analyzed throughout the entire
consolidation phase. No patients were lost to followup, leaving 44 patients (88
femurs). The mean followup was 26 months (range, 14-40 months). The distraction
rate and final length of gain were similar between treated and control limbs. A
priori power analysis suggested that 44 legs were required in each group to
achieve statistical significance of 0.05 with 90% power to detect a 50%
difference in treatment effect between treatment and control groups. RESULTS:
There were no differences in hip ROM, knee ROM, or maximal thigh circumference
between the two lower extremities at any time during the study period. VAS scores
were no different between the patients who received BtX-A and those who received
saline. CONCLUSIONS: Local injection of 200 IU BtX-A in the quadriceps muscles
does not appear to reduce distraction-induced pain nor enhance ROM in the hip or
knee during femoral lengthening. Additional studies are needed to evaluate the
effect of larger doses or different injection methods. Based on our findings, we
do not recommend routine use of botulinum injections during limb lengthening and
believe any further use of this drug should only be in the context of a
controlled trial. LEVEL OF EVIDENCE: Level II, therapeutic study.
PMID- 27506972
TI - CORR Insights(r): Two- to 4-year Followup of a Short Stem THA Construct:
Excellent Fixation, Thigh Pain a Concern.
PMID- 27506973
TI - What is the Prevalence of Radiographic Hip Findings Associated With
Femoroacetabular Impingement in Asymptomatic Asian Volunteers?
AB - BACKGROUND: Morphologic features of the proximal femur reminiscent of those seen
in patients with femoroacetabular impingement (FAI) have been reported among
asymptomatic individuals in Western populations, but whether this is the case in
Asian populations is unknown. QUESTIONS/PURPOSES: The purpose of this study was
to determine the prevalence of radiographic findings in the proximal femur that
are consistent with FAI in asymptomatic Korean volunteers. METHODS: Two hundred
asymptomatic volunteers with no prior hip surgery or childhood hip problems
underwent three-view plain radiographs (pelvis AP view, Sugioka view, and 45
degrees Dunn view) of both hips. There were 146 hips from male volunteers and
254 hips from female volunteers in the study. The mean age of all participants
was 34.7 years (range, 21-49 years). Cam-type morphologic features were defined
as the presence of the following on one or more of the three views: pistol-grip
morphologic features, an osseous bump at the femoral head-neck junction,
flattening of the femoral head-neck offset, or alpha angle greater than 55
degrees . Pincer-type morphologic features were determined by radiographic signs,
including crossover sign, deficient posterior wall sign, or lateral center-edge
angle greater than 40 degrees . RESULTS: The prevalence of cam-type morphologic
features seen on at least one radiograph was 38% (male, 57%; female, 26%). The
prevalence of cam-type features (at least one positive cam-type feature) was 2.0%
(male, 6%; female, 0%) on the pelvic AP view, 24% (male, 36%; female, 17%) on the
Sugioka view, and 30% (male, 47%; female, 20%) on the 45 degrees Dunn view. The
prevalence of pincer-type morphologic features (at least one positive pincer-type
feature) was 23% (male, 27%; female, 21%) on the pelvic AP view. CONCLUSION: The
prevalence of FAI-related morphologic features in asymptomatic Asian populations
was comparable to the prevalence in Western populations. Considering the high
prevalence of radiographic hip findings reminiscent of FAI in asymptomatic Asian
populations, it will be important to determine whether FAI-related morphologic
features are a cause of hip pain when considering surgery in Asian patients.
PMID- 27506974
TI - Is the detection of accelerated sea level rise imminent?
AB - Global mean sea level rise estimated from satellite altimetry provides a strong
constraint on climate variability and change and is expected to accelerate as the
rates of both ocean warming and cryospheric mass loss increase over time. In
stark contrast to this expectation however, current altimeter products show the
rate of sea level rise to have decreased from the first to second decades of the
altimeter era. Here, a combined analysis of altimeter data and specially designed
climate model simulations shows the 1991 eruption of Mt Pinatubo to likely have
masked the acceleration that would have otherwise occurred. This masking arose
largely from a recovery in ocean heat content through the mid to late 1990 s
subsequent to major heat content reductions in the years following the eruption.
A consequence of this finding is that barring another major volcanic eruption, a
detectable acceleration is likely to emerge from the noise of internal climate
variability in the coming decade.
PMID- 27506975
TI - Global or Granulosa Cell-Specific Pten Mutations in Combination with Elevated FSH
Levels Fail to Cause Ovarian Tumours in Mice.
AB - Phosphatase and tensin homologue (PTEN) is a known tumour suppressor. To explore
the role of Pten in ovarian tumorigenesis, we used transgenic (Tg) SOX2. Cre and
AMH. Cre mouse models to direct global Pten haploinsufficiency (Pten +/-) or
ovary-specific granulosa cell (GC) Pten disruption (Pten GC ). Pten mutant models
were combined with progressively rising Tg-follicle-stimulating hormone (TgFSH)
levels to study the tumorigenic potential of combined genetic/endocrine
modification in vivo. Global Pten +/- mice exhibited grossly detectable tumours
in multiple organs including uterine and mammary tissue and displayed reduced
survival. Despite extra-ovarian tumorigenesis, Pten +/- females had no detectable
ovarian tumours, although elevated corpus luteum numbers increased ovary size and
estrous cycling was altered. Combined TgFSH/Pten +/- mice also had no ovarian
tumours, but early survival was reduced in the presence of TgFSH. Ovary-specific
Pten GC +/- TgFSH females exhibited no detectable ovarian or uterine tumours,
and corpus luteum numbers and estrous cycling remained unchanged. The non
tumorigenic ovarian phenotypes in Pten +/- and Pten GC +/- TgFSH mice support
the proposal that multi-hit genetic mutations (including ovarian and extra
ovarian tissue) initiate ovarian tumours. Our findings suggest that elevated FSH
may reduce early cancer survival; however, the ovary remains remarkably resistant
to Pten-induced tumorigenic changes even in the presence of uterine and
reproductive cancers.
PMID- 27506976
TI - Selective mitochondrial depletion, apoptosis resistance, and increased mitophagy
in human Charcot-Marie-Tooth 2A motor neurons.
AB - Charcot-Marie-Tooth 2A (CMT2A) is an inherited peripheral neuropathy caused by
mutations in MFN2, which encodes a mitochondrial membrane protein involved in
mitochondrial network homeostasis. Because MFN2 is expressed ubiquitously, the
reason for selective motor neuron (MN) involvement in CMT2A is unclear. To
address this question, we generated MNs from induced pluripotent stem cells
(iPSCs) obtained from the patients with CMT2A as an in vitro disease model. CMT2A
iPSC-derived MNs (CMT2A-MNs) exhibited a global reduction in mitochondrial
content and altered mitochondrial positioning without significant differences in
survival and axon elongation. RNA sequencing profiles and protein studies of key
components of the apoptotic executioner program (i.e. p53, BAX, caspase 8,
cleaved caspase 3, and the anti-apoptotic marker Bcl2) demonstrated that CMT2A
MNs are more resistant to apoptosis than wild-type MNs. Exploring the balance
between mitochondrial biogenesis and the regulation of autophagy-lysosome
transcription, we observed an increased autophagic flux in CMT2A-MNs that was
associated with increased expression of PINK1, PARK2, BNIP3, and a splice variant
of BECN1 that was recently demonstrated to be a trigger for mitochondrial
autophagic removal. Taken together, these data suggest that the striking
reduction in mitochondria in MNs expressing mutant MFN2 is not the result of
impaired biogenesis, but more likely the consequence of enhanced mitophagy. Thus,
these pathways represent possible novel molecular therapeutic targets for the
development of an effective cure for this disease.
PMID- 27506977
TI - Transcriptome-wide effects of a POLR3A gene mutation in patients with an unusual
phenotype of striatal involvement.
AB - RNA polymerase III is essential for the transcription of non-coding RNAs,
including tRNAs. Mutations in the genes encoding its largest subunits are known
to cause hypomyelinating leukodystrophies (HLD7) with pathogenetic mechanisms
hypothesised to involve impaired availability of tRNAs. We have identified a
founder mutation in the POLR3A gene that leads to aberrant splicing, a premature
termination codon and partial deficiency of the canonical full-length transcript.
Our clinical and imaging data showed no evidence of the previously reported white
matter or cerebellar involvement; instead the affected brain structures included
the striatum and red nuclei with the ensuing clinical manifestations. Our
transcriptome-wide investigations revealed an overall decrease in the levels of
Pol III-transcribed tRNAs and an imbalance in the levels of regulatory ncRNAs
such as small nuclear and nucleolar RNAs (snRNAs and snoRNAs). In addition, the
Pol III mutation was found to exert complex downstream effects on the Pol II
transcriptome, affecting the general regulation of RNA metabolism.
PMID- 27506979
TI - HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth
in a model of achondroplasia.
AB - Mutations that cause increased and/or inappropriate activation of FGFR3 are
responsible for a collection of short-limbed chondrodysplasias. These mutations
can alter receptor trafficking and enhance receptor stability, leading to
increased receptor accumulation and activity. Here, we show that wildtype and
mutant activated forms of FGFR3 increase expression of the cytoplasmic
deacetylase HDAC6 (Histone Deacetylase 6) and that FGFR3 accumulation is
compromised in cells lacking HDAC6 or following treatment of fibroblasts or
chondrocytes with small molecule inhibitors of HDAC6. The reduced accumulation of
FGFR3 was linked to increased FGFR3 degradation that occurred through a lysosome
dependent mechanism. Using a mouse model of Thanatophoric Dysplasia Type II
(TDII) we show that both HDAC6 deletion and treatment with the small molecule
HDAC6 inhibitor tubacin reduced FGFR3 accumulation in the growth plate and
improved endochondral bone growth. Defective endochondral growth in TDII is
associated with reduced proliferation and poor hypertrophic differentiation and
the improved bone growth was associated with increased chondrocyte proliferation
and expansion of the differentiation compartment within the growth plate. These
findings further define the mechanisms that control FGFR3 accumulation and
contribute to skeletal pathology caused by mutations in FGFR3.
PMID- 27506978
TI - Overlap of abnormal photoreceptor development and progressive degeneration in
Leber congenital amaurosis caused by NPHP5 mutation.
AB - Ciliary defects can result in severe disorders called ciliopathies. Mutations in
NPHP5 cause a ciliopathy characterized by severe childhood onset retinal
blindness, Leber congenital amaurosis (LCA), and renal disease. Using the canine
NPHP5-LCA model we compared human and canine retinal phenotypes, and examined the
early stages of photoreceptor development and degeneration, the kinetics of
photoreceptor loss, the progression of degeneration and the expression profiles
of selected genes. NPHP5-mutant dogs recapitulate the human phenotype of very
early loss of rods, and relative retention of the central retinal cone
photoreceptors that lack function. In mutant dogs, rod and cone photoreceptors
have a sensory cilium, but develop and function abnormally and then rapidly
degenerate; L/M cones are more severely affected than S-cones. The lack of outer
segments in mutant cones indicates a ciliary dysfunction. Genes expressed in
mutant rod or both rod and cone photoreceptors show significant downregulation,
while those expressed only in cones are unchanged. Many genes in cell-death and
survival pathways also are downregulated. The canine disease is a non-syndromic
LCA-ciliopathy, with normal renal structures and no CNS abnormalities. Our
results identify the critical time points in the pathogenesis of the
photoreceptor disease, and bring us closer to defining a potential time window
for testing novel therapies for translation to patients.
PMID- 27506982
TI - Cytokine genes as potential biomarkers for muscle weakness in OPMD.
AB - Molecular biomarkers emerge as an accurate diagnostic tool, but are scarce for
myopathies. Lack of outcome measures sensitive to disease onset and symptom
severity hamper evaluation of therapeutic developments. Cytokines are circulating
immunogenic molecules, and their potential as biomarkers has been exploited in
the last decade. Cytokines are released from many tissues, including skeletal
muscles, but their application to monitor muscle pathology is sparse. We report
that the cytokine functional group is altered in the transcriptome of
oculopharyngeal muscular dystrophy (OPMD). OPMD is a dominant, late-onset
myopathy, caused by an alanine-expansion mutation in the gene encoding for
poly(A) binding protein nuclear 1 (expPABPN1). Here, we investigated the
hypothesis that cytokines could mark OPMD disease state. We determined cytokines
levels the vastus lateralis muscle from genetically confirmed expPABPN1 carriers
at a symptomatic or a presymptomatic stage. We identified cytokine-related genes
candidates from a transcriptome study in a mouse overexpressing exp PABPN1 Six
cytokines were found to be consistently down-regulated in OPMD vastus lateralis
muscles. Expression levels of these cytokines were highly correlated in controls,
but this correlation pattern was disrupted in OPMD. The levels of these 6
cytokines were not altered in expPABPN1 carriers at a pre-symptomatic stage,
suggesting that this group of cytokines is a potential biomarker for muscle
weakness in OPMD. Correlation pattern of expression levels could be a novel
measurer for disease state.
PMID- 27506985
TI - Lineage tracing reveals conversion of liver sinusoidal endothelial cells into
hepatocytes.
AB - Although liver sinusoidal endothelial cells (LSECs) have long been known to
contribute to liver regeneration following injury, the exact role of these cells
in liver regeneration remains poorly understood. In this work, we performed
lineage tracing of LSECs in mice carrying Tie2-Cre or VE-cadherin-Cre constructs
to facilitate fate-mapping of LSECs in liver regeneration. Some YFP-positive
LSECs were observed to convert into hepatocytes following a two-thirds partial
hepatectomy (PH). Furthermore, human umbilical vein endothelial cells (HUVECs)
could be triggered to convert into cells that closely resembled hepatocytes when
cultured with serum from mice that underwent an extended PH. These findings
suggest that mature non-hepatocyte LSECs play an essential role in mammalian
liver regeneration by converting to hepatocytes. The conversion of LSECs to
hepatocyte-like (iHep) cells may provide a new approach to tissue engineering.
PMID- 27506986
TI - Berberine Reduces Uremia-Associated Intestinal Mucosal Barrier Damage.
AB - Berberine is one of the main active constituents of Rhizoma coptidis, a
traditional Chinese medicine, and has long been used for the treatment of
gastrointestinal disorders. The present study was designed to investigate the
effects of berberine on the intestinal mucosal barrier damage in a rat uremia
model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the
uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6
weeks. To assess the intestinal mucosal barrier changes, blood samples were
collected for measuring the serum D-lactate level, and terminal ileum tissue
samples were used for analyses of intestinal permeability, myeloperoxidase
activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase
(SOD) activity. Berberine treatment resulted in significant decreases in the
serum D-lactate level, intestinal permeability, intestinal myeloperoxidase
activity, and intestinal mucosal and submucosal edema and inflammation, and the
Chiu's scores assessed for intestinal mucosal injury. The intestinal MDA level
was reduced and the intestinal SOD activity was increased following berberine
treatment. In conclusion, berberine reduces intestinal mucosal barrier damage
induced by uremia, which is most likely due to its anti-oxidative activity. It
may be developed as a potential treatment for preserving intestinal mucosal
barrier function in patients with uremia.
PMID- 27506987
TI - Blackberry, raspberry and black raspberry polyphenol extracts attenuate
angiotensin II-induced senescence in vascular smooth muscle cells.
AB - Activation of angiotensin II (Ang II) signaling during aging increases reactive
oxygen species (ROS) leading to vascular senescence, a process linked to the
onset and progression of cardiovascular diseases (CVD). Consumption of fruits and
vegetables, particularly berries, is associated with decreased incidence of CVD,
which has mainly been attributed to the polyphenol content of these foods. Thus,
the objective of this study was to investigate the role of blackberry (BL),
raspberry (RB), and black raspberry (BRB) polyphenol extracts in attenuating Ang
II-induced senescence in vascular smooth muscle cells (VSMCs) and to determine
the molecular mechanisms involved. BL, RB and BRB polyphenol extracts (200 MUg ml
1) attenuated Ang II-induced senescence, denoted by decreased number of cells
positive for senescence associated beta-galactosidase (SA-beta-gal) and down
regulation of p21 and p53 expression, which were associated with decreased ROS
levels and Ang II signaling. BL polyphenol extract increased superoxide dismutase
(SOD) 1 expression, attenuated the up-regulation of Nox1 expression and the
phosphorylation of Akt, p38MAPK and ERK1/2 induced by Ang II, and reduced
senescence in response to Nox1 overexpression. In contrast, RB and BRB polyphenol
extracts up-regulated the expression of SOD1, SOD2, and glutathione peroxidase 1
(GPx1), but exerted no effect on Nox1 expression nor on senescence induced by
Nox1 overexpression. BRB reduced signaling similar to BL, while RB was unable to
reduce Akt phosphorylation. Furthermore, we demonstrated that inhibition of Akt,
p38MAPK and ERK1/2 as well as down-regulation of Nox1 by siRNA prevented
senescence induced by Ang II. Our findings indicate that Ang II-induced
senescence is attenuated by BL polyphenols through a Nox1-dependent mechanism and
by RB and BRB polyphenols in a Nox1-independent manner, likely by increasing the
cellular antioxidant capacity.
PMID- 27506988
TI - Survivorship and clinical outcome of the minimally invasive Uniglide medial fixed
bearing, all-polyethylene tibia, unicompartmental knee arthroplasty at a mean
follow-up of 7.3years.
AB - BACKGROUND: Medial UKA performed in England and Wales represents seven to 11% of
all knee arthroplasty procedures, and is most commonly performed using mobile
bearing designs. Fixed bearing eliminates the risk of bearing dislocation,
however some studies have shown higher revision rates for all-polyethylene tibial
components compared to those that utilize metal-backed implants. The aim of the
study is to analyse survivorship and maximum eight-year clinical outcome of
medial fixed bearing, Uniglide unicompartmental knee arthroplasty performed using
an all-polyethylene tibial component with a minimal invasive approach. METHODS:
Between 2002 and 2009, 270 medial fixed UKAs were performed in our unit. Patients
were reviewed pre-operatively, five and eight years post-operatively. Clinical
and radiographic reviews were carried out. Patients' outcome scores (Oxford,
WOMAC and American Knee Score) were documented in our database and analysed.
RESULTS: Survival and clinical outcome data of 236 knees with a mean of 7.3years
follow-up are reported. Every patient with less than 4.93years of follow-up
underwent a revision. The patients' average age at the time of surgery was
69.5years. The American Knee Society Pain and Function scores, the Oxford Knee
Score and the WOMAC score all improved significantly. The five-year survival rate
was 94.1% with implant revision surgery as an end point. The estimated 10years of
survival rate is 91.3%. Fourteen patients were revised before the five-year
follow-up. CONCLUSION: Fixed bearing Uniglide UKA with an all-polyethylene tibial
component is a valuable tool in the management of a medial compartment
osteoarthritis, affording good short-term survivorship. Level of evidence IV.
PMID- 27506989
TI - Proposal for a new T-stage classification system for distal cholangiocarcinoma: a
10-institution study from the U.S. Extrahepatic Biliary Malignancy Consortium.
AB - BACKGROUND: Seventh AJCC distal cholangiocarcinoma T-stage classification
inadequately separates patients by survival. This retrospective study aimed to
define a novel T-stage system to better stratify patients after resection.
METHODS: Curative-intent pancreaticoduodenectomies for distal cholangiocarcinoma
(1/2000-5/2015) at 10 US institutions were included. Relationships between tumor
characteristics and overall survival (OS) were assessed and incorporated into a
novel T-stage classification. RESULTS: 176 patients (median follow-up: 24mo) were
included. Current AJCC T-stage was not associated with OS (T1: 23mo, T2: 20mo,
T3: 25mo, T4: 12mo; p = 0.355). Tumor size >=3 cm and presence of lymphovascular
invasion (LVI) were associated with decreased OS on univariate and multivariable
analyses. Patients were stratified into 3 groups [T1: size <3 cm and (-)LVI (n =
69; 39.2%); T2: size >=3 cm and (-)LVI or size <3 cm and (+)LVI (n = 82; 46.6%);
and T3: size >=3 cm and (+)LVI (n = 25; 14.2%)]. Each progressive proposed T
stage was associated with decreased median OS (T1: 35mo; T2: 20mo; T3: 8mo; p =
0.002). CONCLUSION: Current AJCC distal cholangiocarcinoma T-stage does not
adequately stratify patients by survival. This proposed T-stage classification,
based on tumor size and LVI, better differentiates patient outcomes after
resection and could be considered for incorporation into the next AJCC distal
cholangiocarcinoma staging system.
PMID- 27506990
TI - Optimal use of hepatobiliary scintigraphy before liver resection.
PMID- 27506991
TI - Validation of the peak bilirubin criterion for outcome after partial hepatectomy.
AB - INTRODUCTION: Postoperative liver failure (PLF) is a dreaded complication after
partial hepatectomy. The peak bilirubin criterion (>7.0 mg/dL or >=120 MUmol/L)
is used to define PLF. This study aimed to validate the peak bilirubin criterion
as postoperative risk indicator for 90-day liver-related mortality. METHODS:
Characteristics of 956 consecutive patients who underwent partial hepatectomy at
the Maastricht University Medical Centre or Royal Free London between 2005 and
2012 were analyzed by uni- and multivariable analyses with odds ratios (OR) and
95% confidence intervals (95%CI). RESULTS: Thirty-five patients (3.7%) met the
postoperative peak bilirubin criterion at median day 19 with a median bilirubin
level of 183 [121-588] MUmol/L. Sensitivity and specificity for liver-related
mortality after major hepatectomy were 41.2% and 94.6%, respectively. The
positive predictive value was 22.6%. Predictors of liver-related mortality were
the peak bilirubin criterion (p < 0.001, OR = 15.9 [95%CI 5.2-48.7]), moderate
severe steatosis and fibrosis (p = 0.013, OR = 8.5 [95%CI 1.6-46.6]), ASA 3-4 (p
= 0.047, OR = 3.0 [95%CI 1.0-8.8]) and age (p = 0.044, OR = 1.1 [95%CI 1.0-1.1]).
CONCLUSION: The peak bilirubin criterion has a low sensitivity and positive
predictive value for 90-day liver-related mortality after major hepatectomy.
PMID- 27506992
TI - Robotic and open distal pancreatectomy with celiac axis resection for locally
advanced pancreatic body tumors: a single institutional assessment of
perioperative outcomes and survival.
AB - BACKGROUND: Distal pancreatectomy with celiac axis resection (DP-CAR) is an
option for T4 tumors of the pancreatic body. We examined the perioperative and
oncologic outcomes of open and robotic DP-CAR at a high-volume pancreatic center.
METHODS: Retrospective review of all consecutive DP-CARs. Patient demographics,
90-day perioperative outcomes, and disease specific survival were collected.
RESULTS: 30 DP-CARs were performed (11 Robotic, 19 Open). Both groups had similar
preoperative/tumor characteristics, and 27 of 28 PDA patients received
neoadjuvant chemotherapy. Robotic DP-CAR was associated with decreased OT (316
vs. 476 min), reduced EBL (393 vs. 1736 ml) and lower rates of blood transfusion
(0% vs. 54%) (all p < 0.05). No robotic DP-CAR required conversion. Both groups
had similar rates of 90-day mortality, major morbidity, LOS, readmission, and
receipt of adjuvant therapy. Similarly, both approaches were associated with high
R0 resection rates (82% vs. 79%). At a median follow-up of 33 months, median
overall survival for the PDA cohort was 35 months, with no difference in the
robotic and open approach (33 and 40 months, p = 0.310). CONCLUSIONS: With a
median survival approaching 3 years, DP-CAR represents an effective treatment for
select patients with locally advanced pancreatic body cancer, regardless of
approach.
PMID- 27506994
TI - Classification and techniques of en bloc venous reconstruction for
pancreaticoduodenectomy.
AB - BACKGROUND: Surgical resection is the only cure for hepato-pancreato-biliary
(HPB) malignancy. In the era of multidisciplinary approaches and neoadjuvant
therapies for locally advanced, borderline resectable tumors, the feasibility and
efficacy of en bloc vascular resection has been validated across multiple
studies. However, the variability of venous anatomy within the perihepatic and
peri-portal regions necessitates familiarity with alternative resection and
reconstruction techniques appropriate to the specific region of tumor invasion.
METHODS: To organize these paradigms, the venous system has been divided into
five zones: 1) hepatic hilum; 2) hepatoduodenal ligament; 3) portal vein/splenic
vein confluence, which is further subdivided into right (3a) and left (3b); 4)
infra-confluence; and 5) splenic vein. RESULTS: This study systematically
analyzes the anatomic considerations and clinical scenarios specific to each zone
to organize the necessary preparative maneuvers, surgical procedures, and
vascular reconstruction techniques to achieve an R0 resection. The anatomic and
tumor-specific factors which deem a specimen unresectable are also explored.
Surgical videos demonstrating these techniques are presented. DISCUSSION:
Preparation and familiarity with venous reconstruction maneuvers is essential for
an oncologically effective operation, and can be safely achieved by utilizing
this logical anatomic and procedural framework.
PMID- 27506993
TI - Outcome of surgery for recurrent pyogenic cholangitis: a single center
experience.
AB - BACKGROUND: Although, recurrent pyogenic cholangitis (RPC) is prevalent in
several parts of India, there is paucity of published literature from India. The
aim of this study was to report on the short and long-term outcomes of surgery
for RPC. METHODS: All the patients, who underwent surgery for RPC between August
2007 and February 2016 in the Department of Surgical gastroenterology, Institute
of Postgraduate Medical Education and Research, Kolkata, India were
retrospectively reviewed. RESULTS: Of the total 94 patients, 66 (70%) were women.
The median age at presentation was 40 years. Left lobe was solely involved in 49%
of patients. Left hepatectomy was performed in 23/44 (52%) patients who underwent
liver resection. Thirty two postoperative complications developed in 27 patients
(29%). Complete stone clearance was possible in 83% of patients after primary
surgery. Over a median follow up of 36 months, seventy one of 87 patients (81%)
remained free of stones. Recurrent cholangitis occurred 10 of 87 patients (11%).
CONCLUSIONS: Surgery plays an important role in the management of RPC achieving
excellent short and long-term outcomes.
PMID- 27506995
TI - Patterns of hepatic resections in North America: use of concurrent partial
resections and ablations.
AB - BACKGROUND: National registries have not adequately captured concurrent partial
hepatic resections or ablations. Therefore, the aim of this analysis was to
describe the patterns of concurrent partial resections and ablations in North
America. METHODS: Patients undergoing a hepatic resection were identified using
the American College of Surgeons-National Surgical Quality Improvement Program
Targeted Hepatectomy database. Perioperative outcomes were compared for patients
undergoing concurrent "wedge" resections and/or ablations and other subsets.
RESULTS: A total of 2714 patients were identified who met inclusion criteria.
Major hepatectomy was performed in 1037 patients (38.2%) while partial lobectomy
was performed in 1677 (61.8%) patients. Concurrent "wedge" hepatic resections and
ablations were undertaken in 56.0% and 14.2% of patients, respectively, and were
more frequently performed among patients undergoing a partial lobectomy and among
patients undergoing surgery for colorectal liver metastasis (both p < 0.001).
While associated with a decreased incidence of postoperative complications (p =
0.027) and liver failure (p = 0.031) among patients undergoing a major
hepatectomy, concurrent therapies were associated with comparable 30-day outcomes
for patients undergoing partial lobectomy. CONCLUSION: Concurrent "wedge" hepatic
resections and ablations are performed in 56.0% and 14.2%, respectively of
patients undergoing hepatectomy. Concurrent procedures were not associated with
worse clinical outcomes.
PMID- 27506996
TI - Erratum to: The continuous performance test (rCPT) for mice: a novel operant
touchscreen test of attentional function.
PMID- 27506997
TI - Cannabinoid-induced depression of synaptic transmission is switched to
stimulation when dopaminergic tone is increased in the globus pallidus of the
rodent.
AB - Because activation of D2 receptors reverses the neurochemical effects of
cannabinoids, we examined whether increasing dopaminergic tone in the globus
pallidus (GPe) switches cannabinoid induced depression of synaptic transmission.
GABAergic synaptic currents evoked in pallidal neurons by stimulation of striatal
projections (IPSCs) were depressed by perfusion with the CB1R agonist ACEA.
Coactivation of D2Rs with quinpirole converted the depression into stimulation.
Pretreatment with pertussis toxin (PTX) to limit Gi/o protein coupling also
switched the CB1R-induced depression of IPSCs. The stimulation of IPSCs was
blocked by the selective PKA blocker H89. Changes in the paired pulse ratio
during both inhibitory and stimulatory responses indicate that the effects are
due to changes in transmitter release. Postsynaptic depolarization induces
endocannabinoid release that inhibits transmitter release (DSI). When D2Rs were
activated with quinpirole, depolarization increased transmission instead of
depressing it. This increase was blocked by AM251. We also examined the effects
of CB1R/D2R coactivation on cAMP accumulation in the GPe to further verify that
the AC/PKA cascade is involved. CB1R/D2R coactivation converted the inhibition of
cAMP seen when each receptor is stimulated alone into a stimulation. We also
determined the effects on turning behavior of unilateral injection of ACEA into
the GPe of awake animals and its modification by dopamine antagonists. Blockade
of D2 family receptors with sulpiride antagonized the motor effects of ACEA. We
show, for the first time, that cannabinoid-inhibition of synaptic transmission in
the GPe becomes a stimulation after D2Rs or PTX treatment and that the switch is
probably relevant for the control of motor behavior.
PMID- 27506998
TI - Concurrent exercise training: do opposites distract?
AB - Specificity is a core principle of exercise training to promote the desired
adaptations for maximising athletic performance. The principle of specificity of
adaptation is underpinned by the volume, intensity, frequency and mode of
contractile activity and is most evident when contrasting the divergent
phenotypes that result after undertaking either prolonged endurance or resistance
training. The molecular profiles that generate the adaptive response to different
exercise modes have undergone intense scientific scrutiny. Given divergent
exercise induces similar signalling and gene expression profiles in skeletal
muscle of untrained or recreationally active individuals, what is currently
unclear is how the specificity of the molecular response is modified by prior
training history. The time course of adaptation and when 'phenotype specificity'
occurs has important implications for exercise prescription. This context is
essential when attempting to concomitantly develop resistance to fatigue (through
endurance-based exercise) and increased muscle mass (through resistance-based
exercise), typically termed 'concurrent training'. Chronic training studies
provide robust evidence that endurance exercise can attenuate muscle hypertrophy
and strength but the mechanistic underpinning of this 'interference' effect with
concurrent training is unknown. Moreover, despite the potential for several key
regulators of muscle metabolism to explain an incompatibility in adaptation
between endurance and resistance exercise, it now seems likely that multiple
integrated, rather than isolated, effectors or processes generate the
interference effect. Here we review studies of the molecular responses in
skeletal muscle and evidence for the interference effect with concurrent training
within the context of the specificity of training adaptation.
PMID- 27506999
TI - miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3
and is negatively regulated by lncRNA CHRF.
AB - Silicosis is an incurable occupational disease associated with inflammation,
fibroblast proliferation and the accumulation of extracellular matrix in lung
tissues. The dysregulation of lncRNAs and miRNAs has been implicated in many
complex diseases; however, the current understanding of their roles in fibrotic
lung diseases, especially silicosis, remains limited. Our previous microRNA
(miRNA, miR) microarray data have indicated decreased expression levels of miR
489 in lung tissues of silica-induced pulmonary fibrosis. Here, we further
explored the role of miR-489 in a mouse model of silicosis. Interestingly, miR
489 levels were reduced in both macrophages that were exposed to silica and
fibroblasts that were exposed to TGF-beta1. Additionally, the overexpressed miR
489 carried out its anti-fibrotic role by attenuating inflammation and fibrotic
progression in vivo. Our molecular study further demonstrated that miR-489
inhibited silica-induced pulmonary fibrosis primarily by repressing its target
genes MyD88 and Smad3. Moreover, the up-regulated lncRNA cardiac hypertrophy
related factor (CHRF) reversed the inhibitory effect of miR-489 on MyD88 and
Smad3 and then triggered the inflammation and fibrotic signaling pathways.
Overall, our data indicate that the CHRF-miR-489-MyD88 Smad3 signaling axis
exerts key functions in silica-induced pulmonary fibrosis and may represent a
therapeutic target for silicosis.
PMID- 27507000
TI - Structure and function of methanogenic microbial communities in sediments of
Amazonian lakes with different water types.
AB - Tropical lake sediments are a significant source for the greenhouse gas methane.
We studied function (pathway, rate) and structure (abundance, taxonomic
composition) of the microbial communities (Bacteria, Archaea) leading to methane
formation together with the main physicochemical characteristics in the sediments
of four clear water, six white water and three black water lakes of the Amazon
River system. Concentrations of sulfate and ferric iron, pH and delta13 C of
organic carbon were usually higher, while concentrations of carbon, nitrogen and
rates of CH4 production were generally lower in white water versus clear water or
black water sediments. Copy numbers of bacterial and especially archaeal
ribosomal RNA genes also tended to be relatively lower in white water sediments.
Hydrogenotrophic methanogenesis contributed 58 +/- 16% to total CH4 production in
all systems. Network analysis identified six communities, of which four were
comprised mostly of bacteria found in all sediment types, while two were mostly
in clear water sediment. Terminal restriction fragment length polymorphism (T
RFLP) and pyrosequencing showed that the compositions of the communities differed
between the different sediment systems, statistically related to the particular
physicochemical conditions and to CH4 production rates. Among the archaea, clear
water, white water, and black water sediments contained relatively more
Methanomicrobiales, Methanosarcinaceae and Methanocellales, respectively, while
Methanosaetaceae were common in all systems. Proteobacteria, Deltaproteobacteria
(Myxococcales, Syntrophobacterales, sulfate reducers) in particular,
Acidobacteria and Firmicutes were the most abundant bacterial phyla in all
sediment systems. Among the other important bacterial phyla, clear water
sediments contained relatively more Alphaproteobacteria and Planctomycetes,
whereas white water sediments contained relatively more Betaproteobacteria,
Firmicutes, Actinobacteria, and Chloroflexi than the respective other sediment
systems. The data showed communities of bacteria common to all sediment types,
but also revealed microbial groups that were significantly different between the
sediment types, which also differed in physicochemical conditions. Our study
showed that function of the microbial communities may be understood on the basis
of their structures, which in turn are determined by environmental heterogeneity.
PMID- 27507001
TI - Boosting oxygen reduction/evolution reaction activities with layered perovskite
catalysts.
AB - Layered PrBaMn2O5+delta (H-PBM) was simply prepared by annealing pristine
Pr0.5Ba0.5MnO3-delta in H2. The oxygen reduction/evolution reaction activities
are remarkably enhanced by employing H-PBM. The improvement can be ascribed to
the introduction of additional oxygen vacancies, an optimized eg filling of Mn
ions, and the facile incorporation of oxygen into layered H-PBM.
PMID- 27507002
TI - Associations between body composition, nutrition, and physical activity in young
adults.
AB - OBJECTIVE: The aim of the present study is to investigate the associations
between total energy, macronutrient intakes, and physical activity (PA) and body
composition by assessing body fat mass, fat-free mass, and BMI in a population of
young adults. METHODS: The study population consisted of 605 young Spanish adults
(median age 20.38 +/- 2.67). Body composition, including fat mass and fat-free
mass, was calculated with body composition analyzer. Daily energy and
macronutrient intakes were measured using a 72-h recall method. The International
PA Questionnaire was used to assess PA and sedentary time. Linear regression
analyses were performed to test the possible associations between nutrition, PA
factors, and body composition. RESULTS: Linear regression analyses revealed that
BMI has a significant positive association with protein intake (P = .004, B =
0.088, 95% CI 0.028-0.149) and an inverse association with carbohydrate intake (P
= 0.034, B = -0.027, 95% CI -0.053 - -0.002). Protein intake also demonstrated a
significant association with fat-free mass, but the size of the effect was
smaller (P = .027, B = 96.965, 95% CI 11.250-182.679). There was evidence of a
positive association between total PA and moderate-to-vigorous PA (P < .001, B =
15.630, 95% CI 6.989 -24.270) and fat-free mass (P < .001, B = 20.208, 95% CI
9.694 -30.723). When fat mass was used as the outcome variable, there was no
evidence of any association with the PA, total energy, and macronutrient intakes
variables analyzed. CONCLUSIONS: Our findings suggest that PA variables were
consistently associated with body composition, specifically fat-free mass.
Dietary factors also have influence over body composition; we showed that protein
intake is significantly associated with fat-free mass and BMI.
PMID- 27507003
TI - The effect of the neural activity on topological properties of growing neural
networks.
AB - The connectivity structure in cortical networks defines how information is
transmitted and processed, and it is a source of the complex spatiotemporal
patterns of network's development, and the process of creation and deletion of
connections is continuous in the whole life of the organism. In this paper, we
study how neural activity influences the growth process in neural networks. By
using a two-dimensional activity-dependent growth model we demonstrated the
neural network growth process from disconnected neurons to fully connected
networks. For making quantitative investigation of the network's activity
influence on its topological properties we compared it with the random growth
network not depending on network's activity. By using the random graphs theory
methods for the analysis of the network's connections structure it is shown that
the growth in neural networks results in the formation of a well-known "small
world" network.
PMID- 27507004
TI - ADAMTS13-von Willebrand factor axis is involved in the pathophysiology of kidney
ischaemia-reperfusion injury.
AB - AIM: The ADAMTS13-von Willebrand factor (vWF) axis has been suggested to play a
critical role in the pathophysiology of ischaemia-reperfusion injury (IRI) in the
heart or brain. Therefore, we aimed to investigate whether this axis was involved
in the pathophysiology of IRI-induced acute kidney injury. METHODS: We performed
renal IRI in ADAMTS13 knockout (KO) or wild type (WT) mice. Functional and
histological kidney damage, and inflammation were compared and the effect of anti
vWF antibodies in ADAMTS13 KO mice was assessed. RESULTS: Following IRI, the
blood and kidney ADAMTS13 levels were significantly decreased. vWF expression was
significantly upregulated in both the medulla and cortex of injured kidneys as
shown by immunohistochemistry and western blot analyses. There was also an
increased level of vWF dimers after IRI. In ADAMTS13 KO mice, kidney vWF levels
were further increased and this was associated with greater endothelial and
epithelial injury compared to WT mice, suggesting an important role of vWF in
renal IRI. In addition, the number of Gr-1+ neutrophils was significantly higher
in the kidneys of ADAMTS13 KO mice compared to WT mice, whereas F4/80 macrophage
numbers were unchanged. In ADAMTS13 KO mice, administration of anti-vWF
antibodies after IRI partially reversed renal injury. CONCLUSION: Our data show
that the ADAMTS13-vWF axis is partially involved in the pathophysiology of kidney
IRI, suggesting that regulating ADAMTS13- and vWF-dependent mechanisms could have
therapeutic potential to limit renal IRI.
PMID- 27507005
TI - Pubertal status, pre-meal drink composition, and later meal timing interact in
determining children's appetite and food intake.
AB - Puberty is a period of development that alters energy intake patterns. However,
few studies have examined appetite and food intake (FI) regulation during
development of puberty in children and adolescents. Therefore, the objective was
to measure the effect of pubertal status on FI and subjective appetite after pre
meal glucose and whey protein drinks in 9- to 14-year-old boys and girls. In a
within-subject, randomized, repeated-measures design, children (21 pre-early
pubertal, 15 mid-late pubertal) received equally sweetened drinks containing
Sucralose (control), glucose, or whey protein (0.75 g/kg body weight) in 250 mL
of water 2 h after a standardized breakfast on 6 separate mornings. Ad libitum FI
was measured either 30 or 60 min later and appetite was measured over time. In
pre-early and mid-late pubertal boys and girls there was no effect of sex on
total FI (kcal). Glucose and whey protein drinks reduced calorie intake similarly
at 30 min. But at 60 min, whey protein reduced FI (p < 0.001) compared with
control and glucose in pre-early pubertal children, but not in mid-late pubertal
children. However, sex was a factor (p = 0.041) when FI was expressed per
kilogram body weight. Pubertal status did not affect FI/kilogram body weight in
boys, but it was 32% lower in mid-late pubertal girls than at pre-early puberty
(p = 0.010). Appetite was associated with FI in mid-late pubertal children only.
In conclusion, pubertal development affects appetite and FI regulation in
children.
PMID- 27507006
TI - Food avoidance in athletes: FODMAP foods on the list.
AB - We surveyed 910 athletes to assess behaviours towards self-selected
food/ingredient avoidance to minimize gastrointestinal distress. Fifty-five
percent eliminated at least 1 high fermentable oligosaccharides, disaccharides,
monosaccharides, and polyols (FODMAP) food/category, with up to 82.6% reporting
symptom improvement. In athletes indicating that high FODMAP foods trigger
gastrointestinal symptoms, lactose (86.5%) was most frequently eliminated,
followed by galactooligosaccharides (23.9%), fructose (23.0%), fructans (6.2%),
and polyols (5.4%). Athletes avoid predominantly lactose and to a lesser extent
other high FODMAP foods to reduce gastrointestinal distress.
PMID- 27507007
TI - Association between exercise-induced change in body composition and change in
cardiometabolic risk factors in postmenopausal South Asian women.
AB - The South Asian population suffers from a high prevalence of type 2 diabetes and
cardiovascular disease (CVD). A unique obesity phenotype of elevated visceral
adipose tissue (VAT) is associated with CVD risk among South Asians. Exercise
induced reduction in VAT and body fat is an effective mechanism to improve
cardiometabolic risk factors but this has not been shown in South Asians. Whether
exercise-induced changes in measurements such as waist circumference (WC) are
independently related to changes in cardiometabolic risk factors in South Asians
is unknown. Multi-slice computed tomography scanning was used to assess VAT,
cardiometabolic risk factors through a fasting blood sample, and body fat using
dual-energy X-ray absorptiometry. Forty- nine postmenopausal South Asian women
who participated in two 12-week aerobic exercise programs were included.
Bivariate correlations were used to assess associations between change in
cardiometabolic risk factors and change in body composition. Regression analyses
were conducted with change in glucose, insulin, and homeostatic model assessment
of insulin resistance (HOMA-IR) as dependent variables and change in body
composition as independent variables of interest. There were significant
associations between changes in fasting insulin, glucose, and HOMA-IR with change
in VAT. The association between change in VAT and these cardiometabolic risk
factors was independent of change in other body composition variables of
interest. South Asian women should be encouraged to engage in aerobic activity to
reduce their risk of type 2 diabetes and CVD, and physicians should be aware of
improvements in glucose regulation with exercise training not observed through
reductions in WC.
PMID- 27507008
TI - Compartmentalization in PVC super-phylum: evolution and impact.
AB - BACKGROUND: The PVC super-phylum gathers bacteria from seven phyla
(Planctomycetes, Verrucomicrobiae, Chlamydiae, Lentisphaera, Poribacteria, OP3,
WWE2) presenting different lifestyles, cell plans and environments. Planctomyces
and several Verrucomicrobiae exhibit a complex cell plan, with an
intracytoplasmic membrane inducing the compartmentalization of the cytoplasm into
two regions (pirellulosome and paryphoplasm). The evolution and function of this
cell plan is still subject to debate. In this work, we hypothesized that it could
play a role in protection of the bacterial DNA, especially against Horizontal
Genes Transfers (HGT). Therefore, 64 bacterial genomes belonging to seven
different phyla (whose four PVC phyla) were studied. We reconstructed the
evolution of the cell plan as precisely as possible, thanks to information
obtained by bibliographic study and electronic microscopy. We used a strategy
based on comparative phylogenomic in order to determine the part occupied by the
horizontal transfers for each studied genomes. RESULTS: Our results show that the
bacteria Simkania negevensis (Chlamydiae) and Coraliomargarita akajimensis
(Verrucomicrobiae), whose cell plan were unknown before, are compartmentalized,
as we can see on the micrographies. This is one of the first indication of the
presence of an intracytoplasmic membrane in a Chlamydiae. The proportion of HGT
does not seems to be related to the cell plan of bacteria, suggesting that
compartmentalization does not induce a protection of bacterial DNA against HGT.
Conversely, lifestyle of bacteria seems to impact the ability of bacteria to
exchange genes. CONCLUSIONS: Our study allows a best reconstruction of the
evolution of intracytoplasmic membrane, but this structure seems to have no
impact on HGT occurrences. REVIEWERS: This article was reviewed by Mircea Podar
and Olivier Tenaillon.
PMID- 27507009
TI - Pseudorabies virus can escape from CRISPR-Cas9-mediated inhibition.
AB - The CRISPR-Cas9 system is a newly developed genome-engineering tool used to
inhibit virus infection by targeting the conserved regions of the viral genomic
DNA. In the present study, we constructed a cell line stably expressing Cas9
endonuclease and sgRNA targeting the conserved UL30 gene of pseudorabies virus
(PRV). During the PRV infection, the CRISPR-Cas9 system was efficient in cleaving
the UL30 gene in each passage. However, deletions and insertions occurred at low
passages, while substitutions were frequently observed at high passages.
Furthermore, copy numbers and virus titers of PRV were significantly increased in
a passage-dependent manner, indicating that viral genomic replication and
assembly were more effective at the high passages than at low passages. These
results demonstrated that PRV could escape from CRISPR-Cas9-mediated inhibition.
Therefore, whether the CRISPR-Cas9 system is suitable for antiviral application
should be considered and carefully verified.
PMID- 27507010
TI - ZnO nanorods prepared via ablation of Zn with millisecond laser in liquid media.
AB - ZnO nanomaterials with controlled size, shape and surface chemistry are required
for applications in diverse areas, such as optoelectronics, photocatalysis,
biomedicine and so on. Here, we report on ZnO nanostructures with rod-like and
spherical shapes prepared via laser ablation in liquid using a laser with
millisecond-long pulses. By changing laser parameters (such as pulse width and
peak power), the size or aspect ratio of such nanostructures could be tuned. The
surface chemistry and defects of the products were also strongly affected by
applied laser conditions. The preparation of different structures is explained by
the intense heating of liquid media caused by millisecond-long pulses and
secondary irradiation of already-formed nanostructures.
PMID- 27507011
TI - Imaging mass spectrometry of elements in forensic cases by LA-ICP-MS.
AB - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was
performed to map elements in thin formalin-fixed paraffin-embedded tissue
sections of two forensic cases with firearm and electrocution injuries,
respectively. In both cases, histological examination of the wounded tissue
regions revealed the presence of exogenous aggregates that may be interpreted as
metallic depositions. The use of imaging LA-ICP-MS allowed us to unambiguously
determine the elemental composition of the observed aggregates assisting the
pathologist in case assessments. To the best of our knowledge, we demonstrate for
the first time the use of imaging LA-ICP-MS as a complementary tool for forensic
pathologists and toxicologists in order to map the presence of metals and other
elements in thin tissue sections of post-mortem cases.
PMID- 27507012
TI - [Ingestion of castor seeds in attempting suicide].
PMID- 27507013
TI - [New recommendations of 2016 European Guidelines on cardiovascular disease
prevention].
PMID- 27507014
TI - Efficacy and safety of Dexrazoxane (DRZ) in sarcoma patients receiving high
cumulative doses of anthracycline therapy - a retrospective study including 32
patients.
AB - BACKGROUND: Anthracyclines, as the most effective therapy, are the cornerstone of
advanced stage sarcoma treatment. However, anthracyclines can also contribute to
myocardial dysfunction and congestive heart failure, ultimately limiting the
therapeutic potential of the drug. Coadministration of Dexrazoxane has been shown
to effectively reduce cardiotoxicity, however primarily in patients suffering in
diseases other than sarcoma. METHODS: The aim of this retrospective analysis was
to evaluate safety and efficacy of chemotherapy with high cumulative doses of
anthracyclines in combination with Dexrazoxane. The medical charts of 32 patients
treated in four institutions were analyzed. Reasons for coadministration were
rechallenge, reaching the cumulative anthracycline dose and preexisting heart
failure. RESULTS: The median age was 54 years [18-68 years]. The median
cumulative anthracycline dose before adding DRZ was 450 mg/m(2) and after
administration of last anthracycline containing therapy 750 mg/m(2). Either
during treatment or follow up, 2/27 patients (7 %) without preexisting major
cardiac findings developed anthracycline-induced cardiotoxicity. The median
overall survival (OS) from start of the first anthracycline containing
chemotherapy was 46 months and 17 months from the initial coadministration of
DRZ. At rechallenge, the median progression free survival (PFS) with DRZ was 7
months. In continuous therapy, the median PFS was 13 months from beginning of
chemotherapy and 9 months from the addition of DRZ. CONCLUSION: Chemotherapy with
high cumulative doses of anthracyclines in addition with DRZ demonstrated a
remarkable OS in these advanced disease patients. Cardiac side-effects due to
high cumulative doses of anthracyclines requiring discontinuation of
anthracycline treatment were rare. A PFS of 9 months from the beginning of the
coadministration of DRZ indicates that continuing anthracycline therapy beyond
established cumulative doses is a promising therapeutic option.
PMID- 27507015
TI - Production of hemolysin BL by Bacillus cereus group isolates of dairy origin is
associated with whole-genome phylogenetic clade.
AB - BACKGROUND: Bacillus cereus group isolates that produce diarrheal or emetic
toxins are frequently isolated from raw milk and, in spore form, can survive
pasteurization. Several species within the B. cereus group are closely related
and cannot be reliably differentiated by established taxonomical criteria. While
B. cereus is traditionally recognized as the principal causative agent of
foodborne disease in this group, there is a need to better understand the
distribution and expression of different toxin and virulence genes among B.
cereus group food isolates to facilitate reliable characterization that allows
for assessment of the likelihood of a given isolate to cause a foodborne disease.
RESULTS: We performed whole genome sequencing of 22 B. cereus group dairy
isolates, which represented considerable genetic diversity not covered by other
isolates characterized to date. Maximum likelihood analysis of these genomes
along with 47 reference genomes representing eight validly published species
revealed nine phylogenetic clades. Three of these clades were represented by a
single species (B. toyonensis -clade V, B. weihenstephanensis - clade VI, B.
cytotoxicus - VII), one by two dairy-associated isolates (clade II; representing
a putative new species), one by two species (B. mycoides, B. pseudomycoides -
clade I) and four by three species (B. cereus, B. thuringiensis, B. anthracis -
clades III-a, b, c and IV). Homologues of genes encoding a principal diarrheal
enterotoxin (hemolysin BL) were distributed across all, except the B. cytotoxicus
clade. Using a lateral flow immunoassay, hemolysin BL was detected in 13 out of
18 isolates that carried hblACD genes. Isolates from clade III-c (which included
B. cereus and B. thuringiensis) consistently did not carry hblACD and did not
produce hemolysin BL. Isolates from clade IV (B. cereus, B. thuringiensis)
consistently carried hblACD and produced hemolysin BL. Compared to others, clade
IV was significantly (p = 0.0001) more likely to produce this toxin. Isolates
from clade VI (B. weihenstephanensis) carried hblACD homologues, but did not
produce hemolysin BL, possibly due to amino acid substitutions in different toxin
encoding genes. CONCLUSIONS: Our results demonstrate that production of diarrheal
enterotoxin hemolysin BL is neither inclusive nor exclusive to B. cereus sensu
stricto, and that phylogenetic classification of isolates may be better than
taxonomic identification for assessment of B. cereus group isolates risk for
causing a diarrheal foodborne disease.
PMID- 27507016
TI - Calcinosis cutis universalis.
PMID- 27507017
TI - Excess long-term mortality in outpatient deep venous thrombosis patients managed
in an ambulatory care setting.
AB - Background: Deep venous thrombosis (DVT) is increasingly being managed in the
outpatient setting, particularly patients deemed low-risk at presentation. The
long-term outcomes of these patients remain unclear. Aim: To determine the long
term outcomes of patients with DVT and those with raised D-dimer without DVT
managed exclusively by an ambulatory care pathway. Design: Retrospective cohort
analysis. Methods: 828 consecutive patients assessed at the Ambulatory Care
Clinic of a tertiary care university hospital between 1 January and 31 December
2008 for potential lower limb DVT were analysed. Primary and secondary outcome
was all-cause mortality and new diagnosis of cancer, respectively. Median follow
up was 6.4 years. Results: The final cohort comprised 131 patients with DVT, 396
with raised D-dimer without DVT and 165 with normal D-dimer without DVT. Long
term survival was 72.5% for DVT, 75.3% for elevated D-dimer without thrombosis
and 93.3% for those with normal D-dimer ( P < 0.0001). The risk of death with DVT
remained significant after adjusting for age, gender, previous cancer, recent
surgery and previous thromboembolism (HR 2.17, 95% CI [1.07, 4.38]). Cancer
accounted for 44.4 and 37.8% of deaths within the first and second groups,
respectively. 50% of cancers in the former group were diagnosed during follow-up
vs. 95.1% in the latter. Conclusion: The 5-year survival of patients with DVT
managed via ambulatory care was worse than expected. An algorithm is urgently
needed to identify predictors of adverse outcomes for both these patients as well
as those with raised D-dimer without thrombosis.
PMID- 27507018
TI - Third nerve palsy and internal carotid aneurysm.
PMID- 27507019
TI - Hydroa vacciniforme-like lymphoma.
PMID- 27507021
TI - Genetic and Environmental Influences on Traits of Gender Identity Disorder: A
Study of Japanese Twins Across Developmental Stages.
AB - The present study examined: (1) gender and age differences of mean gender
identity disorder (GID) trait scores in Japanese twins; (2) the validity of the
prenatal hormone transfer theory, which predicts that, in dizygotic (DZ) twin
pairs, twins with an opposite-gender co-twin more frequently exhibit GID traits
than twins with a same-gender co-twin; and (3) the magnitude of genetic and
environmental influences on GID traits as a function of age and gender. Data from
1450 male twin pairs, 1882 female twin pairs, and 1022 DZ male-female pairs
ranging from 3 to 26 years of age were analyzed. To quantify individual variances
in GID traits, each participant completed four questionnaire items based on
criteria for GID from the Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR). Our most important findings were: (1) Japanese females exhibited GID
traits more frequently than males and Japanese children exhibited GID traits less
frequently than adolescents and adults (among females, the prevalence was 1.6 %
in children, 10 % in adolescents, and 12 % in adults; among males, the prevalence
was 0.5, 2, and 3 %, respectively); (2) the data did not support the prenatal
hormone transfer theory for GID traits; and (3) a large part of the variance for
GID traits in children was accounted for by familial factors; however, the
magnitude was found to be greater in children than in adolescents or adults,
particularly among females. This study suggests that although the prevalence is
likely to increase, familial effects are likely to decrease as individuals age.
PMID- 27507020
TI - A Qualitative Investigation of the Impact of a Livelihood Intervention on
Gendered Power and Sexual Risk Behaviors Among HIV-Positive Adults in Rural
Kenya.
AB - Despite the recognized links between food insecurity, poverty, and the risk of
HIV/AIDS, few randomized trials have evaluated the impact of livelihood
interventions on HIV risk behaviors. The current study draws upon data collected
from a qualitative process evaluation that was embedded into a pilot randomized
controlled trial that tested whether a multisectoral agricultural intervention
(Shamba Maisha) affected the HIV-related health of HIV-positive adults in rural
Kenya. In the current study, we drew upon longitudinal, in-depth interviews with
45 intervention participants and nine control participants (N = 54) in order to
examine the impacts of the intervention on gendered power and sexual risk
reduction among both women and men. Female and male participants in the
intervention described positive changes in sexual practices and gendered power
dynamics as a result of intervention participation. Changes included reduced
sexual risk behaviors, improved gender-related power dynamics, and enhanced
quality of intimate relationships. These findings illuminate how a multisectoral
agricultural intervention may affect inequitable gender relations and secondary
transmission risk. Further research is needed to explore how to best leverage
agricultural interventions to address the important intersections between poverty
and inequitable gender relations that shape HIV risks.
PMID- 27507022
TI - Chronic Physical Illness Burden and Suicidal Ideation Among Dominicans in New
York City.
AB - Little is known about the association between chronic illness and suicidal
ideation (SI) among Dominicans living in the United States. This study used data
from a community survey of 2753 Dominican adults in New York City. SI included
thoughts of self-harm or being better off dead in the past month. Chronic
physical illness burden was categorized as having 0, 1, or 2+ diagnosed
conditions. Adjusted logistic regressions evaluated the association between
number of conditions and SI, overall and stratified by sex and age. Adjusted
models yielded a strong association between chronic illness burden and SI among
men [odds ratio (OR) 5.57, 95 % confidence interval (CI) 2.19-14.18] but not
women (OR 0.80, 95 % CI 0.50-1.29; interaction p = 0.011). The association of
interest did not differ significantly between younger and older adults. Screening
for SI in health care practice, particularly among Dominican men with multiple
chronic health conditions, may be warranted.
PMID- 27507023
TI - Establishment and application of an analytical in-house database (IHDB) for rapid
discrimination of Bacillus subtilis group (BSG) using whole-cell MALDI-TOF MS
technology.
AB - Members of the Bacillus subtilis group (BSG) possess industrial applicability;
unfortunately, B. subtilis and its phylogenetically closest species are
indistinguishable from one another using 16S rDNA sequencing, physiological and
biochemical tests. Matrix-assisted laser desorption ionization-time of flight
mass spectrometry (MALDI-TOF MS) is a relatively novel technique for the fast and
reliable identification of microorganisms. The aim of this study was to construct
a unique analytical in-house database (IHDB) for BSG discrimination based on
whole-cell protein fingerprinting using MALDI-TOF MS, as well as to discover
biomarkers from the MS peaks to generate a classification model for further
differentiation using the ClinProTools software. Type strains of 12 species
(included five subspecies) of the BSG were used to build a main spectrum profile
(MSP) to create an IHDB under the optimized parameters. The BSG isolates obtained
from partial recA gene sequencing were used for IHDB validation. A total of 84
(100%) isolates were correctly identified to the species level and had high score
values (mean score: 2.52). However, the IHDB had ambiguous identification at the
subspecies level of Bacillus amyloliquefaciens. After implementation of the
classification models, the strains could be clearly differentiated. We have
successfully developed a rapid, accurate and cost-effective platform for the
species- and subspecies-level discrimination of BSG based on the implementation
of the IHDB and coupled with ClinProTools, which can be employed as an
alternative technology to DNA sequencing and applied for efficient quality
control of the microbial agent.
PMID- 27507024
TI - [Not Available].
PMID- 27507025
TI - [Not Available].
PMID- 27507026
TI - [Not Available].
PMID- 27507027
TI - [Fluordeoxyglukose-PET/CT af angiosarkom i aorta].
PMID- 27507028
TI - [Dermatological laser- and light treatments of scars].
AB - Many patients struggle with tender, rigid and erythematous scars. Various
modalities are used to treat cutaneous scars and in recent years, laser
treatments are emerging as promising procedures. This article describes laser
systems used for scar treatment according to scar type, evaluates the highest
available level of evidence from randomized controlled trials (RCTs) and
introduces a guideline for laser treatment of scars. Twelve RCTs documented
effect on acne, burn and surgical scars. It is recommended that laser- and light
based treatments are considered according to the scar type.
PMID- 27507029
TI - [Clinical trial informed consent information for participants can be improved].
AB - Informed consent has been a legal right for patients participating in clinical
research and an obligation for health professionals for a long time. A growing
body of literature suggests that a considerable share of research participants do
not read or understand the information they are given, or do not base their
decisions on trial participation on the information. This article points out the
challenges for health professionals arising from this situation and offers
suggestions for how professionals can deal with the challenges.
PMID- 27507030
TI - [An ordinary condom can be used for removing encircling metallic objects around
penis].
AB - We describe a new method for removing encircling objects from penis. A 69-year
old male was admitted with a ratchet spanner stuck at the penile base. A condom
was applied to the penile shaft and manoeuvred in between the ratchet spanner and
the penis. A lot of lubrication was applied, and the ratchet spanner was removed.
Later the same method was tried when a 66-year-old male had a tap aerator stuck
under glans penis. However, the method was unsuccessful because of a very narrow
diameter of the tap aerator. Instead, the tap aerator was cut in two by using an
angle grinder.
PMID- 27507031
TI - [Therapeutic management of poorly differentiated neuroendocrine lung tumors and
neuroendocrine carcinomas of the digestive system].
AB - Poorly differentiated neuroendocrine tumors are rare but their incidence is
rising. High-grade neuroendocrine lung tumors, including small-cell lung cancer,
are part of this group. Outside of the lung, they most often arise within the
gastrointestinal tract (oesophagus, guts and pancreas) and are called
neuroendocrine carcinomas. Due to their rarity, very little is known about
neuroendocrine carcinomas of the pancreas and the gastrointestinal tract and few
studies have been done. Therefore, most therapeutic recommendations are issued
from studies on small-cell lung cancers. Histological scores have grown more
accurate these past few years: poorly differentiated neuroendocrine tumors
regroup various entities such as small-cells, large-cells and mix tumors, which
seem to have different prognosis. They are diagnosed at a metastatic state in
more than 50 % of cases. In localised disease, surgery is performed on selected
patients. Adjuvant chemotherapy is administered in poorly differentiated
neuroendocrine tumors of the lung and is an option in neuroendocrine carcinomas,
without proof of efficacy. If not operable, radiochemotherapy is done for tumors
of the lung, rectum, and eosophagus. If the disease is diagnosed at a metastatic
state, chemotherapy is administered with a combination of platin salts (cisplatin
or carboplatin) and etoposide. In poorly differentiated neuroendocrine tumors of
the lung, prophylactic cranial irradiation is performed in localized disease if
there is a good response to chemotherapy. Even if these therapies have improved
the overall survival, no improvement has been made during the past four decades
and the prognosis remains low.
PMID- 27507032
TI - Use of routine histopathology and factor VIII-related antigen/von Willebrand
factor immunohistochemistry to differentiate primary hemangiosarcoma of bone from
telangiectatic osteosarcoma in 54 dogs.
AB - Hemangiosarcoma (HSA) of bone and telangiectatic osteosarcoma (tOSA) can appear
similar histologically, but differ in histogenesis (malignant endothelial cells
versus osteoblasts), and may warrant different treatments. Immunohistochemistry
(IHC) for endothelial cell marker factor VIII-related antigen/von Willebrand
factor (FVIII-RAg/vWF) is a well-documented ancillary test to confirm HSA
diagnoses in soft tissues, but its use in osseous HSA is rarely described.
Archived samples of 54 primary appendicular bone tumours previously diagnosed as
HSA or tOSA were evaluated using combination routine histopathology (RHP) and
IHC. Approximately 20% of tumours were reclassified on the basis of FVIII-RAg/vWF
immunoreactivity, typically from an original diagnosis of tOSA to a reclassified
diagnosis of HSA. No sample with tumour osteoid clearly identified on RHP was
immunopositive for FVIII-RAg/vWF. RHP alone was specific but not sensitive for
diagnosis of HSA, compared with combination RHP and IHC. Routine
histopathological evaluation in combination with FVIII-RAg/vWF IHC can help
differentiate canine primary appendicular HSA from tOSA.
PMID- 27507033
TI - Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid
arthritis.
AB - BACKGROUND: The concerns about the development of adverse events (AEs) in elderly
RA patients as a result of age-related changes in drug metabolism and the
presence of comorbid illnesses are emphasizing due to increasing prevalence of
rheumatoid arthritis (RA) in old age. However, they tend to be inadequately
represented in RA clinical trials because of the exclusion criteria that are
commonly applied. The tolerability and safety of TNF inhibitors in elderly
patients have not been also evaluated in clinical practice. This study aimed to
evaluate the retention rate and safety of TNF inhibitors (TNFI) in elderly RA
patients. METHODS: Total 429 RA patients (838 person-years [PYs]) treated with
TNFI from a retrospective biologic DMARDs registry. Patients were divided into an
elderly (age >=60 years) and a younger group (<60 years). The drug retention
rates of both groups were compared using Kaplan-Meier curves. Potential
predictors of TNFI discontinuation in the elderly were examined using Cox
regression analysis. The incidence rate (IR) of serious adverse events (SAEs) in
the elderly group was compared to that of the young group. RESULTS: Of the
patients, 24.9 % (n = 107, 212 PYs) were in the elderly group. Regarding the
retention rates of TNFI in 3 years, there was no significant difference between
the elderly and younger group (p = 0.33). The major cause of discontinuation in
elderly patients was AE (34.3 %), whereas that was drug ineffectiveness (41.7 %)
in younger patients. Age (HR 1.09, CI 1.02-1.16) was a predictor of
discontinuation, while the presence of comorbidity (HR 0.37, CI 0.15-0.91) had a
protective effect against drug discontinuation in the elderly. The IR of SAEs in
the elderly (6.13/100 PYs) was higher than in the younger group (5.11/100 PYs).
CONCLUSIONS: The retention rate of TNFI in the elderly was comparable with that
in younger patients. The major cause of discontinuation in the elderly patients
was AEs, while it was drug ineffectiveness in younger patients. The IR of SAEs in
the elderly was higher than in the younger patients.
PMID- 27507034
TI - Measuring and understanding motivation among community health workers in rural
health facilities in India-a mixed method study.
AB - BACKGROUND: Motivated human resource is the key to improve health system
performance and retention of health workers. There is scanty literature on
measuring motivation of health workers in India. Thus, the objective of this
study was to measure and identify important aspects of health workers' motivation
in North India. METHODS: A mixed method study design was adopted. Under the
quantitative component, we interviewed randomly selected 62 community health
workers (CHWs) in 18 sub-centres in two blocks of District Ambala, Haryana, India
using a structured motivation scale. In-depth interviews were also carried out
with 18 CHWs to explore the sources of motivation. RESULTS: The age of
respondents and training in the past 12 months were found to be significantly
associated with motivation. Job burnout, poor personal health, job insecurity and
less career development opportunities were the individual level de-motivators,
whereas not being able to fulfil family roles and poor supportive supervision
were identified as environmental factors for poor motivation. Love for work, and
financial incentives were individual level motivators, while community support
and recognition, organizational commitment and pride, regular training were
identified as environmental level motivators. CONCLUSION: Non-financial
motivators such as interpersonal relations, family support, skill and career
development opportunities require more attention. Regular need-based training is
essential to maintain high levels of motivation.
PMID- 27507035
TI - Five boosts to GP funding.
PMID- 27507036
TI - Association of rs10811656 on 9P21.3 with the risk of coronary artery disease in a
Chinese population.
AB - BACKGROUND: Genome-wide association studies have reported that the 9p21.3 locus
confers risk for coronary artery disease (CAD). However, it is not known whether
rs10811656 is linked with CAD in a Chinese population. Thus, the purpose of this
study was to investigate the potential association between rs10811656 and the
risk of CAD in a Chinese population. METHODS: We conducted a hospital-based, case
control study with 251 CAD patients and 304 controls to examine the potential
association of rs10811656 with CAD. RESULTS: The frequencies of the TT genotypes
in CAD cases were significantly different from those in controls (adjusted OR:
1.96, 95 % CI: 1.09-3.505, P = 0.024). Compared to controls, rs10811656 was
significantly associated with the stable angina pectoris (adjusted OR: 1.42, 95 %
CI: 1.06-1.90, P = 0.017), but not with acute coronary syndrome. There was also a
highly significant association of rs10811656 with double-vessel and triple-vessel
disease when patients were divided into subgroups based on the number of diseased
vessels (adjusted OR: 1.68 and 1.60, 95 % CI: 1.14-2.44 and 1.10-2.33, P = 0.009
and 0.02, respectively). CONCLUSION: Our results suggest that the rs10811656
locus might be associated with CAD in a Chinese Han population.
PMID- 27507037
TI - Lack of pharmacokinetic drug-drug interaction between ramucirumab and irinotecan
in patients with advanced solid tumors.
AB - PURPOSE: The objective of this phase II study was to evaluate the potential of
pharmacokinetic (PK) drug-drug interactions between ramucirumab and irinotecan or
its metabolite, SN-38, when administered with folinic acid and 5-fluorouracil
(FOLFIRI). METHODS: Patients received intravenous infusions of FOLFIRI and
ramucirumab 8 mg/kg on Day 1 of a 2-week cycle. FOLFIRI was administered alone in
Cycle 1; ramucirumab followed by FOLFIRI was administered in all subsequent
cycles. Blood was collected at regular intervals after infusions in Cycles 1 and
2 to determine irinotecan, SN-38, and ramucirumab concentrations. PK parameters
were derived by noncompartmental analysis. RESULTS: Twenty-nine patients received
treatment. The dose-normalized area under the concentration versus time curve
from zero to infinity [AUC(0-infinity)] and the maximum observed concentration (C
max) of irinotecan and SN-38 were comparable between Cycle 1 (FOLFIRI alone) and
Cycle 2 (ramucirumab + FOLFIRI). The ratios of geometric least squares (LS) means
for irinotecan were 0.93 (90 % CI 0.83-1.05) for AUC(0-infinity) and 1.04 (90 %
CI 0.97-1.12) for C max. The ratios of geometric LS means for SN-38 were 0.95 (90
% CI 0.88-1.04) for AUC(0-infinity) and 0.97 (90 % CI 0.85-1.12) for C max. The
most common treatment-emergent adverse events, regardless of grade, were fatigue
(19 patients, 65.5 %), diarrhea, (16 patients, 55.2 %), and neutropenia (15
patients, 51.7 %). Grade >=3 neutropenia was reported in 7 (24.1 %) patients.
CONCLUSIONS: There was no PK drug-drug interaction between ramucirumab and
irinotecan or its metabolite, SN-38. Ramucirumab with FOLFIRI was well tolerated
in this study, with no new safety concerns.
PMID- 27507038
TI - Systematic assessment of pharmaceutical prescriptions in association with cancer
risk: a method to conduct a population-wide medication-wide longitudinal study.
AB - It is a public health priority to identify the adverse and non-adverse
associations between pharmaceutical medications and cancer. We search for and
evaluate associations between all prescribed medications and longitudinal cancer
risk in participants of the Swedish Cancer Register (N = 9,014,975). We
associated 552 different medications with incident cancer risk (any, breast,
colon, and prostate) during 5.5 years of follow-up (7/1/2005-12/31/2010) in two
types of statistical models, time-to-event and case-crossover. After multiple
hypotheses correction and replication, 141 (26%) drugs were associated with any
cancer in a time-to-event analysis constraining drug exposure to 1 year before
first cancer diagnosis and adjusting for history of medication use. In a case
crossover analysis, 36 drugs (7%) were associated with decreased cancer risk. 12
drugs were found in common in both analyses with concordant direction of
association. We found 14, 10, 7% of all drugs associated with colon, prostate,
and breast cancers in time-to-event models. We only found 1, 2%, and 0% for these
cancers, respectively, in case-crossover analyses. Pharmacoepidemiologic analyses
of cancer risk are sensitive to modeling choices and false-positive findings are
a threat. Medication-wide analyses using different analytical models may help
suggest consistent signals of increased cancer risk.
PMID- 27507039
TI - [The ReWiKs project : Current results of research into participation
opportunities for adults with disabilities in the area of sexual self
determination].
AB - Several studies point to various barriers in achieving sexual self-determination
for people with disabilities as well as a high degree of thematic uncertainty
among staff in residential homes. In addition, women with disabilities and people
in institutions are especially at risk in a particular way, to be victims of
sexual violence. The ReWiKs project develops, based on evaluated guidelines for
sexual self-determination, materials in order to reflect the institutional
handling of the subject. Training modules and recommendations are also developed.
In addition, extracts of materials are created in simple language. All materials
are evaluated before their publication in an intensive theory-practice dialogue.
PMID- 27507040
TI - Lunar influence on prey availability, diet shifts and niche overlap between
Engraulidae larvae in tropical mangrove creeks.
AB - The influence of the lunar cycle on prey availability, diet shifts and overlap
between larval Anchovia clupeoides and Cetengraulis edentulus was evaluated in
mangrove creeks of the Goiana Estuary. Copepod eggs were highly abundant in the
first and last quarter, at the full moon and zoea of Ucides cordatus (Ocypodidae)
in the new moon. The Engraulidae larvae fed on microcrustaceans, algae and early
planktonic stages of benthic organisms. The relative importance of prey varied
according to prey availability in all moon phases. Larval diets were more even in
the full and new moons, when the relative importance of calanoid copepods and
zoeae of U. cordatus as food items increased (index of relative importance, >80%
IRI ). Mangrove creeks were very important feeding grounds for engraulid larvae
during spring tides. Larval diets were more diverse in the first and last-quarter
moon and included protozoeae of Caridean shrimp, larvae of Anomalocardia
brasiliana (Veneridae), Isopoda, Gastropoda, ephippium of Daphnia sp. and nauplii
of Cirripedia, Harpacticoidia and cyclopoid Copepoda. The last five items were
not found in the creeks, suggesting feeding in the main channel. During neap
tides, mangrove creeks were probably also used as refugia. These larvae are
opportunistic and feed on highly available prey and both species feed on the same
items, leading to high dietary overlap in all moon phases. The lunar cycle, which
is related to the spring-neap tidal cycle, was the major driver of quantitative
and qualitative changes in feeding of engraulid larvae on a short time scale.
PMID- 27507042
TI - Cytoskeletal impairment during isoamyl alcohol-induced cell elongation in budding
yeast.
AB - Isoamyl alcohol (IAA) induces pseudohyphae including cell elongation in the
budding yeast Saccharomyces cerevisiae. Detailed regulation of microtubules and
actin in developmental transition during cell elongation is poorly understood.
Here, we show that although IAA did not affect the intracellular actin level, it
reduced the levels of both alpha- and beta-tubulins. In budding yeast,
cytoplasmic microtubules are linked to actin via complexes consisting of at least
Kar9, Bim1, and Myo2, and reach from the spindle pole body to the cortical
attachment site at the bud tip. However, IAA did not affect migration of Myo2 to
the bud tip and kept Kar9 in the interior portion of the cell. In addition, bud
elongation was observed in Kar9-overexpressing cells in the absence of IAA. These
results indicate that impairment of the link between cytoplasmic microtubules and
actin is possibly involved in the lowered interaction of Myo2 with Kar9. Our
study might explain the reason for delayed cell cycle during IAA-induced cell
elongation.
PMID- 27507043
TI - Evaluation of the effects of multiple providers in complex surgical
interventions.
AB - In contrast to new medicinal products, surgical interventions have many features
that complicate their formal assessment through Randomised Clinical Trials. For
example, surgery is delivered by multidisciplinary teams; hence, differential
effects on the outcome are not solely caused by differences in the leading
operator's skill but are also induced by surgical team differences and patient
characteristics. This study focuses on how statistical methods can be used to
accommodate the multicomponent nature of the delivery of surgical interventions.
Hierarchical models with cross-classifications between components of surgery,
applied to historic datasets, can be used during the trial planning phase to
establish the effects and interactions between different components. Methods are
illustrated using two influential components of the intervention, the surgeon and
the anaesthetist, in a cohort of cardiac surgery cases. The statistical
implications for trial design and analysis are presented. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27507044
TI - Early programming of the oocyte epigenome temporally controls late prophase I
transcription and chromatin remodelling.
AB - Oocytes are arrested for long periods of time in the prophase of the first
meiotic division (prophase I). As chromosome condensation poses significant
constraints to gene expression, the mechanisms regulating transcriptional
activity in the prophase I-arrested oocyte are still not entirely understood. We
hypothesized that gene expression during the prophase I arrest is primarily
epigenetically regulated. Here we comprehensively define the Drosophila female
germ line epigenome throughout oogenesis and show that the oocyte has a unique,
dynamic and remarkably diversified epigenome characterized by the presence of
both euchromatic and heterochromatic marks. We observed that the perturbation of
the oocyte's epigenome in early oogenesis, through depletion of the dKDM5 histone
demethylase, results in the temporal deregulation of meiotic transcription and
affects female fertility. Taken together, our results indicate that the early
programming of the oocyte epigenome primes meiotic chromatin for subsequent
functions in late prophase I.
PMID- 27507045
TI - Sebaceous mantleoma (mantle adenoma): reappraisal of the myth of the problematic
benign neoplasm with sebaceous mantle differentiation.
AB - Few cases of a true benign neoplasm with sebaceous mantle differentiation have
been reported, and little is known about this tumor. Herein, we present a rare
case of the neoplasm called sebaceous mantleoma, along with a comparison of the
histology and immunoprofile with those of normal sebaceous mantles. A
pedunculated polyp occurred on the scalp of a 51-year-old woman.
Histopathologically, the tumor showed lobulated epithelial-mesenchymal units that
were separated from the normal dermis by clefts. The lesion was composed of cords
and columns of basaloid cells containing a few mature sebocytes, with a focal
connection to infundibulocystic structures as well as dense fibrotic or
fibromyxoid stroma. Immunohistochemically, androgen receptor, estrogen receptor,
and CD117 were partially positive for the tumor, and CD8 (C8/144B) and epithelial
membrane antigen were focally positive. Additionally, cytokeratin 20-positive
Merkel cells were individually admixed in the tumor nests as well as in normal
sebaceous mantles. This case report reveals the characteristic histology and
immunoprofile of this problematic benign neoplasm and helps to understand this
entity.
PMID- 27507046
TI - RAD51 inhibition in triple negative breast cancer cells is challenged by
compensatory survival signaling and requires rational combination therapy.
AB - The molecular rationale to induce synthetic lethality, by targeting defective
homologous recombination repair in triple negative breast cancer (TNBC), has
proven to have several shortcomings. Not meeting the expected minimal outcomes in
clinical trials has highlighted common clinical resistance mechanisms including;
increased expression of the target gene PARP1, increased expression or reversion
mutation of BRCA1, or up-regulation of the compensatory homologous recombination
protein RAD51. Indeed, RAD51 has been demonstrated to be an alternative synthetic
lethal target in BRCA1-mutated cancers. To overcome selective pressure on DNA
repair pathways, we examined new potential targets within TNBC that demonstrate
synthetic lethality in association with RAD51 depletion. We confirmed
complementary targets of PARP1/2 and DNA-PK as well as a new synthetic lethality
combination with p38. p38 is considered a relevant target in breast cancer, as it
has been implicated in resistance to chemotherapy, including tamoxifen. We show
that the combination of targeting RAD51 and p38 inhibits cell proliferation both
in vitro and in vivo, which was further enhanced by targeting of PARP1. Analysis
of the molecular mechanisms revealed that depletion of RAD51 increased ERK1/2 and
p38 signaling. Our results highlight a potential compensatory mechanism via p38
that limits DNA targeted therapy.
PMID- 27507047
TI - UHRF1 regulates global DNA hypomethylation and is associated with poor prognosis
in esophageal squamous cell carcinoma.
AB - BACKGROUND: Global DNA hypomethylation contributes to oncogenesis through various
mechanisms. The level of long interspersed nucleotide element-1 (LINE- 1)
methylation is considered a surrogate marker of global DNA methylation, and is
attracting interest as a good predictor of cancer prognosis. However, the
mechanism how LINE-1 (global DNA) methylation is controlled in cancer cells
remains to be fully elucidated. Ubiquitin-like with PHD and RING finger domain 1
(UHRF1) plays a crucial role in DNA methylation. UHRF1 is overexpressed in many
cancers, and UHRF1 overexpression may be a mechanism underlying DNA
hypomethylation in cancer cells. Nonetheless, the relationship between UHRF1,
LINE-1 methylation level, and clinical outcome in esophageal squamous cell
carcinoma (ESCC) remains unclear. RESULTS: In ESCC cell lines, vector-mediated
UHRF1 overexpression caused global DNA (LINE-1) hypomethylation and, conversely,
UHRF1 knockdown using siRNA increased the global DNA methylation level. In ESCC
tissues, UHRF1 expression was significantly associated with LINE-1 methylation
levels. Furthermore, UHRF1 overexpression correlated with poor prognosis in our
cohort of 160 ESCC patients. MATERIALS AND METHODS: The relationships between
UHRF1 expression and LINE-1 methylation level (i.e., global DNA methylation
level) were investigated using ESCC tissues and cell lines. In addition, we
examined the correlation between UHRF1 expression, LINE-1 methylation, and
clinical outcome in patients with ESCC. CONCLUSIONS: Our results suggest that
UHRF1 is a key epigenetic regulator of DNA methylation and might be a potential
target for cancer treatment.
PMID- 27507050
TI - The truncated somatostatin receptor sst5TMD4 stimulates the angiogenic process
and is associated to lymphatic metastasis and disease-free survival in breast
cancer patients.
AB - The truncated somatostatin receptor sst5TMD4 is associated with poor prognosis in
breast cancer and increases breast cancer cell malignancy. Here, we examined the
cellular/molecular mechanisms underlying this association, aiming to identify new
molecular tools to improve diagnosis, prognosis or therapy. A gene expression
array comparing sst5TMD4 stably-transfected MCF-7 cells and their controls (empty
plasmid) revealed the existence of profound alterations in the expression of
genes involved in key tumoral processes, such as cell survival or angiogenesis.
Moreover, sst5TMD4-overexpressing MCF-7 and MDA-MB-231 cells demonstrated
increased expression/production of pro-angiogenic factors and enhanced capacity
to form mammospheres. Consistently, sst5TMD4-expressing MCF-7 cells induced
xenografted tumors with higher VEGF levels and elevated number of blood vessels.
Importantly, sst5TMD4 was expressed in a subset of breast cancers, where it
correlated with angiogenic markers, lymphatic metastasis, and reduced disease
free survival. These results, coupled to our previous data, support a relevant
role of sst5TMD4 in the angiogenic process and reinforce the role of sst5TMD4 in
breast cancer malignancy and metastatic potential, supporting its possible
utility to develop new molecular biomarkers and drug therapies for these tumors.
PMID- 27507052
TI - Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer
cells through TGF-beta/Smad signaling pathway.
AB - OBJECTIVE: To investigate the effect of antisense non-coding RNA in the INK4
locus (ANRIL) on invasion and metastasis of thyroid cancer (TC). RESULTS: ANRIL
expression was significantly up-regulated in TC tissues and cells (P < 0.001),
and ANRIL expression was significantly different regarding histological grade and
LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation,
invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can
be reversed by TGF-beta1 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a
in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P <
0.001), and TGF-beta1 siRNA could reverse the ANRIL siRNA induced increase of
p15INK4b; expressions of TGF-beta1 and p-Smad2/3 were increased after silencing
ANRIL (both P < 0.05). MATERIALS AND METHODS: TC and adjacent normal tissues were
collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT
PCR. The siRNA ANRIL and siRNA TGF-beta1 were constructed for TPC-1 and SW579
cell line transfection: si-ANRIL group, si-TGF-beta1 group, si-ANRIL + si-TGF
beta1 group, negative control group and blank group. Effects of ANRIL silencing
on proliferation, invasion and metastasis of TC cells was detected by MTT assay,
Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF
beta1 and p-Smad2/3 expressions in TGF-beta/Smad signaling pathway were detected
by western blot. CONCLUSIONS: ANRIL may reduce p15INK4B expression through
inhibiting TGF-beta/Smad signaling pathway, promoting invasion and metastasis of
TC cells, and the silencing of ANRIL inhibits the invasion and metastasis of TPC
1 cells.
PMID- 27507053
TI - The Fanconi anemia pathway controls oncogenic response in hematopoietic stem and
progenitor cells by regulating PRMT5-mediated p53 arginine methylation.
AB - The Fanconi anemia (FA) pathway is involved in DNA damage and other cellular
stress responses. We have investigated the role of the FA pathway in oncogenic
stress response by employing an in vivo stress-response model expressing the
Gadd45beta-luciferase transgene. Using two inducible models of oncogenic
activation (LSL-K-rasG12D and MycER), we show that hematopoietic stem and
progenitor cells (HSPCs) from mice deficient for the FA core complex components
Fanca or Fancc exhibit aberrant short-lived response to oncogenic insults.
Mechanistic studies reveal that FA deficiency in HSPCs impairs oncogenic stress
induced G1 cell-cycle checkpoint, resulting from a compromised K-rasG12D-induced
arginine methylation of p53 mediated by the protein arginine methyltransferase 5
(PRMT5). Furthermore, forced expression of PRMT5 in HSPCs from LSL-K
rasG12D/CreER-Fanca-/- mice prolongs oncogenic response and delays leukemia
development in recipient mice. Our study defines an arginine methylation
dependent FA-p53 interplay that controls oncogenic stress response.
PMID- 27507054
TI - GDF11 administration does not extend lifespan in a mouse model of premature
aging.
AB - GDF11 has recently emerged as a powerful anti-aging candidate, found in young
blood, capable of rejuvenating a number of aged tissues, such as heart, skeletal
muscle and brain. However, recent reports have shown contradictory data
questioning its capacity to reverse age-related tissue dysfunction. The
availability of a mouse model of accelerated aging, which shares most of the
features occurring in physiological aging, gives us an excellent opportunity to
test in vivo therapies aimed at extending lifespan both in pathological and
normal aging. On this basis, we wondered whether the proposed anti-aging
functions of GDF11 would have an overall effect on longevity. We first confirmed
the existence of a reduction in GDF11/8 levels in our mouse model of accelerated
aging compared with wild-type littermates. However, we show herein that GDF11
daily administration does not extend lifespan of premature-aged mice.
PMID- 27507055
TI - Incidence and relative risk of hemorrhagic events associated with ramucirumab in
cancer patients: a systematic review and meta-analysis.
AB - The purpose of this study was to investigate the overall incidence and relative
risk (RR) of hemorrhagic events in cancer patients treated with ramucirumab. 298
potentially relevant citations on ramucirumab from Pubmed, Web of Science and the
Cochrane Database, as well as abstracts presented at conferences (all up to March
2016) were identified through our initial search. Only phase II and III
prospective clinical trials of ramucirumab among cancer patients with toxicity
records on hemorrhagic events were selected for final analysis. Data was
extracted from the original studies by two independent reviewers. The overall
incidence, RR, and 95% confidence intervals (CI) were calculated using fixed or
random effects models according to the heterogeneity of the enrolled studies. The
statistical analysis was performed by STATA version 11.0 (Stata Corporation,
College Station, TX). 4963 patients with a variety of solid tumors from eleven
eligible studies were selected into our analysis. The results demonstrated that
the overall incidences of all-grade and high-grade hemorrhagic events in cancer
patients were 27.6% (95% CI, 18.7-36.5%) and 2.3% (95% CI, 1.3-3.2%),
respectively. The RR of hemorrhagic events of ramucirumab compared to control was
significantly increased for low-grade (RR, 2.06; 95% CI, 1.85-2.29, p < 0.001),
but not for high-grade (RR, 1.19, 95% CI, 0.80-1.76, p=0.39) hemorrhagic events.
Hemorrhagic events associated with ramucirumab are modest and manageable while
patients could continue to receive ramucizumab treatment to achieve their maximum
clinical benefits.
PMID- 27507056
TI - First-in-human phase I clinical trial of RG7356, an anti-CD44 humanized antibody,
in patients with advanced, CD44-expressing solid tumors.
AB - Transmembrane glycoprotein CD44 is overexpressed in various malignancies.
Interactions between CD44 and hyaluronic acid are associated with poor prognosis,
making CD44 an attractive therapeutic target. We report results from a first-in
human phase I trial of RG7356, a recombinant anti-CD44 immunoglobulin G1
humanized monoclonal antibody, in patients with advanced CD44-expressing solid
malignancies.Sixty-five heavily pretreated patients not amenable to standard
therapy were enrolled and received RG7356 intravenously biweekly (q2w) or weekly
(qw) in escalating doses from 100 mg to 2,250 mg. RG7356 was well tolerated. Most
frequent adverse events were fever, headache and fatigue. Dose-limiting
toxicities included headache (1,500 mg q2w and 1,350 mg qw) and febrile
neutropenia (2,250 mg q2w). The maximum tolerated dose with q2w dosing was 1,500
mg, but was not defined for qw dosing due to early study termination. Clinical
efficacy was modest; 13/61 patients (21%) experienced disease stabilization
lasting a median of 12 (range, 6-35) weeks. No apparent dose- or dose schedule
dependent changes in biological activity were reported from blood or tissue
analyses. Tumor-targeting by positron emission tomography (PET) using 89Zr
labeled RG7356 was observed for doses >=200 mg (q2w) warranting further
investigation of this agent in combination regimens.
PMID- 27507057
TI - Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer
cells.
AB - Breast cancer is the disease with the highest impact on global health, being
metastasis the main cause of death. To metastasize, carcinoma cells must
reactivate a latent program called epithelial-mesenchymal transition (EMT),
through which epithelial cancer cells acquire mesenchymal-like traits.Glypican-3
(GPC3), a proteoglycan involved in the regulation of proliferation and survival,
has been associated with cancer. In this study we observed that the expression of
GPC3 is opposite to the invasive/metastatic ability of Hs578T, MDA-MB231, ZR-75-1
and MCF-7 human breast cancer cell lines. GPC3 silencing activated growth, cell
death resistance, migration, and invasive/metastatic capacity of MCF-7 cancer
cells, while GPC3 overexpression inhibited these properties in MDA-MB231 tumor
cell line. Moreover, silencing of GPC3 deepened the MCF-7 breast cancer cells
mesenchymal characteristics, decreasing the expression of the epithelial marker E
Cadherin. On the other side, GPC3 overexpression induced the mesenchymal
epithelial transition (MET) of MDA-MB231 breast cancer cells, which re-expressed
E-Cadherin and reduced the expression of vimentin and N-Cadherin. While GPC3
inhibited the canonical Wnt/beta-Catenin pathway in the breast cancer cells, this
inhibition did not have effect on E-Cadherin expression. We demonstrated that the
transcriptional repressor of E-Cadherin - ZEB1 - is upregulated in GPC3 silenced
MCF-7 cells, while it is downregulated when GPC3 was overexpressed in MDA-MB231
cells. We presented experimental evidences showing that GPC3 induces the E
Cadherin re-expression in MDA-MB231 cells through the downregulation of ZEB1.Our
data indicate that GPC3 is an important regulator of EMT in breast cancer, and a
potential target for procedures against breast cancer metastasis.
PMID- 27507058
TI - Chemoprevention of intestinal tumorigenesis by the natural dietary flavonoid
myricetin in APCMin/+ mice.
AB - Myricetin is a natural dietary flavonoid compound. We evaluated the efficacy of
myricetin against intestinal tumorigenesis in adenomatous polyposis coli multiple
intestinal neoplasia (APCMin/+) mice. Myricetin was given orally once a day for
12 consecutive weeks. APCMin/+ mice fed with myricetin developed fewer and
smaller polyps without any adverse effects. Histopathological analysis showed a
decreased number of dysplastic cells and degree of dysplasia in each polyp.
Immunohistochemical and western blot analysis revealed that myricetin selectively
inhibits cell proliferation and induces apoptosis in adenomatous polyps. The
effects of myricetin were associated with a modulation the GSK-3beta and Wnt/beta
catenin pathways. ELISA analysis showed a reduced concentration of pro
inflammatory cytokines IL-6 and PGE2 in blood, which were elevated in APCMin/+
mice. The effect of myricetin treatment was more prominent in the adenomatous
polyps originating in the colon. Further studies showed that myricetin
downregulates the phosphorylated p38 MAPK/Akt/mTOR signaling pathways, which may
be the mechanisms for the inhibition of adenomatous polyps by myricetin. Taken
together, our data show that myricetin inhibits intestinal tumorigenesis through
a collection of biological activities. Given these results, we suggest that
myricetin could be used preventatively to reduce the risk of developing colon
cancers.
PMID- 27507059
TI - Superior efficacy of co-treatment with the dual PI3K/mTOR inhibitor BEZ235 and
histone deacetylase inhibitor Trichostatin A against NSCLC.
AB - Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death
worldwide. NSCLC development and progression have recently been correlated with
the heightened activation of histone deacetylases (HDACs) and PI3K/Akt signaling
pathways. Targeted inhibition of these proteins is promising approach for the
development of novel therapeutic strategies to treat patients with advanced
NSCLC. For this reason, we combined a dual PI3K and mTOR inhibitor, BEZ235 with
the HDAC inhibitor Trichostatin A (TSA), to determine their combined effects on
human NSCLC. In this study, we initially discovered that co-treatment with BEZ235
and TSA showed a synergistic effect on inhibition of NSCLC cell proliferation and
induction of apoptosis. The combination treatment also synergistically suppressed
NSCLC migration, invasion and the NSCLC epithelial-mesenchymal transition (EMT)
in vitro. The synergistic effect was also evidenced by declines in xenograft
growth and metastasis rates and in ki-67 protein expression in vivo. Together,
these results indicated that BEZ235 and TSA combination treatment significantly
increased anti-tumor activities compared with BEZ235 and TSA alone, supporting a
further evaluation of combination treatment for NSCLC.
PMID- 27507060
TI - Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth
and metastasis through reduction in survival and invasion factors.
AB - We reported that knockdown of the antisense noncoding mitochondrial RNAs
(ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not
normal cells, suggesting this approach for selective therapy against different
types of cancer. In order to translate these results to a preclinical scenario,
we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed
in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display
structures similar to the human counterparts, including long double-stranded
regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs
with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10
cell proliferation and induces apoptosis in vitro through downregulation of pro
survival and metastasis markers, particularly survivin. For in vivo studies,
subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically
with specific and control antisense oligonucleotides (ASO). For metastasis
studies, tumors were resected, followed by systemic administration of ASOs and
the presence of metastatic nodules in lungs and liver was assessed. Treatment
with specific ASO inhibited tumor growth and metastasis after primary tumor
resection. In a metastasis-only assay, mice inoculated intravenously with cells
and treated with the same ASO displayed reduced number and size of melanoma
nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs
could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs
are the first potential non-nuclear targets for melanoma therapy.
PMID- 27507061
TI - A novel approach to assessing bisphenol-A hazards using an in vitro model system.
AB - BACKGROUND: Although the toxicological impacts of the xenoestrogen bisphenol-A
(BPA) have been studied extensively, but the mechanism of action is poorly
understood. Eventually, no standard method exists for evaluating the possible
health hazards of BPA exposure. Considering mice spermatozoa as a potential in
vitro model, we investigated the effects of BPA exposure (0.0001, 0.01, 1, and
100 MUM for 6 h) on spermatozoa and the related mechanisms of action. The same
doses were also employed to evaluate protein profiles of spermatozoa as a means
to monitor their functional affiliation to diseases. RESULTS: Our results
demonstrated that high concentrations of BPA negatively affect sperm motility,
viability, mitochondrial functions, and intracellular ATP levels by activating
the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein
kinase-A pathways. Moreover, short-term exposure of spermatozoa to high
concentrations of BPA induced differential expressions of 24 proteins. These
effects appeared to be caused by protein degradation and phosphorylation in
spermatozoa. Proteins differentially expressed in spermatozoa from BPA treatment
groups are putatively involved in the pathogenesis of several diseases, mainly
cancer, carcinoma, neoplasm, and infertility. CONCLUSIONS: Based on these
results, we propose that BPA adversely affects sperm function by the activation
of several kinase pathways in spermatozoa. In addition, BPA-induced changes in
the sperm proteome might be partly responsible for the observed effects in
spermatozoa, subsequently involve in the pathogenesis of many diseases.
Therefore, we anticipated that current strategy might broadly consider for the
health hazards assessment of other toxicological agents.
PMID- 27507063
TI - Diagnostic utility of arborizing stromal meshwork fragments in mucinous tumors.
AB - INTRODUCTION: Arborizing stromal meshwork fragments (ASMFs) have been proposed as
a useful clue to differentiate mucin associated with mucinous adenocarcinoma from
contaminating mucus during endobronchial ultrasound-guided transbronchial needle
aspiration. Our aim was to retrospectively review cytology cases with mucinous
material to determine the utility of ASMFs in diagnosing mucinous tumors.
MATERIAL AND METHODS: Diff-Quik stained smears from archival cytology cases (N =
40) were reviewed, including adenocarcinomas with mucinous features, cystic
mucinous neoplasms, and control cases with mucin contamination. Specimens were
procured by image-guided fine needle aspiration (FNA) (16 cases), endoscopic
ultrasound-guided FNA (22 cases), pathologist-performed FNA (1 case), and fluid
drainage (1 case). All cases were reviewed for ASMFs, which were defined as
metachromatic, spidery extensions with frayed edges within a background of
mucinous material. RESULTS: ASMFs were identified in 4 (10% of cases, 14% of
adenocarcinomas) cases of metastatic gastrointestinal mucinous adenocarcinomas in
various locations (liver, lymph node, lung, and bone), but absent in mucin
contamination. ASMFs in Diff-Quik stained smears were magenta-colored and
corresponded to intervening stroma between dissecting mucin in the tumor.
Nonarborizing desmoplastic stroma, inspissated mucus, cartilage fragments,
transgressing vessels in renal cell carcinoma, and mucus-like material in
pancreatic pseudocysts can morphologically mimic ASMFs. CONCLUSION: These data
show that ASMFs may be encountered in some (14%) cases of adenocarcinoma with
mucinous differentiation. When present, ASMFs can be diagnostically helpful to
differentiate adenocarcinoma with mucinous features from contaminating mucus, if
reliably distinguished from mimics. Diagn. Cytopathol. 2016;44:805-810. (c) 2016
Wiley Periodicals, Inc.
PMID- 27507064
TI - Bleeding complications with oral anticoagulants in the elderly: an observational
study.
AB - Over recent years, new oral anticoagulant agents (NOAC) have been commercialized
as a new treatment in order to prevent or treat thromboembolic events. Although
the use of NOACs is easier than for vitamin K antagonists (VKA), their risk
benefit balance still raises concerns, especially in the elderly. To evaluate
bleeding complications with anticoagulants agents (NOAC and VKA) among a
geriatric population. A retrospective study performed in the four units of the
acute geriatric department of CHU Charleroi (116 beds). All the patients who
received at least one dose of oral anticoagulant (NOAC or VKA) during their
hospitalization between January 1st 2013 and May 31th 2014 were enrolled. Medical
files of 242 patients were analyzed, and the type and severity of bleeding were
recorded. Mean age was 84 +/- 5.4 years old. Seventy-three percent were
prescribed VKA. Rivaroxaban was the most prescribed NOAC among this population.
Atrial fibrillation was the primary indication of oral anticoagulation in 73%
with VKA and 94% with NOAC. Fourty-six patients presented a bleeding (38 patients
(22% of patients with VKA) with VKA and 8 patients with NOAC (12% of patients
with NOAC)). We found 13 major bleedings with VKA and only one with NOAC. The
results of this study are encouraging concerning the utilization of NOACs in the
geriatric population. However, larger studies are needed to confirm this.
PMID- 27507062
TI - Fine-mapping analysis revealed complex pleiotropic effect and tissue-specific
regulatory mechanism of TNFSF15 in primary biliary cholangitis, Crohn's disease
and leprosy.
AB - Genetic polymorphism within the 9q32 locus is linked with increased risk of
several diseases, including Crohn's disease (CD), primary biliary cholangitis
(PBC) and leprosy. The most likely disease-causing gene within 9q32 is TNFSF15,
which encodes the pro-inflammatory cytokine TNF super-family member 15, but it
was unknown whether these disparate diseases were associated with the same
genetic variance in 9q32, and how variance within this locus might contribute to
pathology. Using genetic data from published studies on CD, PBC and leprosy we
revealed that bearing a T allele at rs6478108/rs6478109 (r(2) = 1) or rs4979462
was significantly associated with increased risk of CD and decreased risk of
leprosy, while the T allele at rs4979462 was associated with significantly
increased risk of PBC. In vitro analyses showed that the rs6478109 genotype
significantly affected TNFSF15 expression in cells from whole blood of controls,
while functional annotation using publicly-available data revealed the broad cell
type/tissue-specific regulatory potential of variance at rs6478109 or rs4979462.
In summary, we provide evidence that variance within TNFSF15 has the potential to
affect cytokine expression across a range of tissues and thereby contribute to
protection from infectious diseases such as leprosy, while increasing the risk of
immune-mediated diseases including CD and PBC.
PMID- 27507065
TI - The role of hand hygiene in controlling norovirus spread in nursing homes.
AB - BACKGROUND: Norovirus, the leading cause of gastroenteritis, causes higher
morbidity and mortality in nursing homes (NHs) than in the community. Hence,
implementing infection control measures is crucial. However, the evidence on the
effectiveness of these measures in NH settings is lacking. Using an innovative
data-driven modeling approach, we assess various interventions to control
norovirus spread in NHs. METHODS: We collected data on resident and staff
characteristics and inter-human contacts in a French NH. Based on this data, we
developed a stochastic compartmental model of norovirus transmission among the
residents and staff of a 100-bed NH. Using this model, we investigated how the
size of a 100-day norovirus outbreak changed following three interventions:
increasing hand hygiene (HH) among the staff or residents and isolating
symptomatic residents. RESULTS: Assuming a baseline staff HH compliance rate of
15 %, the model predicted on average 19 gastroenteritis cases over 100 days among
the residents, which is consistent with published incidence data in NHs.
Isolating symptomatic residents was highly effective, leading to an 88 %
reduction in the predicted number of cases. The number of expected cases could
also be reduced significantly by increasing HH compliance among the staff; for
instance, by 75 % when assuming a 60 % HH compliance rate. While there was a
linear reduction in the predicted number of cases when HH practices among
residents increased, the achieved impact was less important. CONCLUSIONS: This
study shows that simple interventions can help control the spread of norovirus in
NHs. Modeling, which has seldom been used in these settings, may be a useful tool
for decision makers to design optimal and cost-effective control strategies.
PMID- 27507066
TI - Evolution of hypothalamic lipoma after Roux-en-Y gastric bypass.
AB - Severe obesity is a common consequence of hypothalamic region diseases and their
treatment. Only two previous case reports have described hypothalamic lipomas in
children with obesity. We described a case of an adult with severe obesity
associated with hypothalamic lipoma attached to the third ventricle floor who
underwent Roux-en-Y gastric bypass. He lost 38 and 59 kg at 6 and 12 months after
surgery, respectively. Weight loss after bariatric surgery was as expected in
this patient with severe obesity. At 6 and 12 months, brain magnetic resonance
imaging (MRI) showed stability in lipoma's size.
PMID- 27507067
TI - Trends in vitamin, mineral and dietary supplement use in Switzerland. The CoLaus
study.
AB - BACKGROUND/OBJECTIVES: Vitamin/mineral (VMS) and dietary supplements (DS) use is
common in Switzerland, but nothing is known regarding the factors associated with
their initiation, discontinuation or continuation of intake. SUBJECTS/METHODS:
Prospective study conducted between 2003-2006 and 2009-2012 in Lausanne,
Switzerland among 4676 participants (2525 women, age range 35-75 years). VMS were
defined as single or multivitamin/multimineral preparations; DS were defined as
any dietary supplement. RESULTS: VMS use was 20.6% at baseline and 20.3% at
follow-up (P=0.69): 559 (12.0%) participants discontinued; 545 (11.7%) initiated
and 404 (8.6%) continued VMS use. On multivariable analysis, men had a lower
relative risk ratio (RRR) of discontinuing, initiation or continuing; older age
and being physically active were associated with a higher RRR of initiation or
continuing; lower education and higher body mass index were associated with a
lower RRR of discontinuing or continuing of VMS. DS use decreased from 10.4 to
6.8% (P<0.001): 405 (8.7%) participants discontinued; 239 (5.1%) initiated and 81
(1.7%) continued DS use. On multivariable analysis, men had a lower RRR of
discontinuing, initiation or continuing; older age had a higher RRR of
initiation, discontinuing or continuing; being physically active was associated
with a higher RRR of initiation or continuing; Swiss citizens and former smokers
had a higher RRR of discontinuing. CONCLUSIONS: VMS use is stable in the Lausanne
population, whereas DS use appears to be decreasing. Individuals can be
categorized either as users or non-users depending on the study period, and
consistent users are only a small fraction of prevalent users.
PMID- 27507068
TI - The prevalence of sarcopenia before and after correction for DXA-derived fat-free
adipose tissue.
AB - The literature suggests that the estimate of lean mass may be overestimated in
the obese using dual-energy X-ray absorptiometry (DXA), as ~15% of adipose tissue
is composed of fat-free tissue. The purpose of this study was to investigate how
the DXA-derived fat-free adipose influences appendicular lean mass and prevalence
of sarcopenia across a range of body fat % in both men and women using a national
sample (n=1946). The appendicular lean mass/m2 went from 7.0 kg/m2 (confidence
interval (CI): 6.9, 7.2) to 5.9 kg/m2 (CI: 5.8, 6.1) following correction in
those with ?35% body fat, whereas it only went from 7.5 kg/m2 (CI: 7.2, 7.8) to
7.1 kg/m2 (CI: 6.8, 7.4) following correction in those with <25% body fat. Fat
free adipose tissue may need to be accounted for when estimating appendicular
lean mass and failure to account for fat-free adipose tissue may underestimate
the prevalence of sarcopenia.
PMID- 27507069
TI - Assessment of drug administration via feeding tube and the knowledge of health
care professionals in a university hospital.
AB - BACKGROUND/OBJECTIVES: The use of drugs via feeding tube is problematic.
Appropriate techniques must be used during the administration to prevent
obstruction of a feeding tube, to avoid inadequate drug effects and to minimize
the risk of toxicity of the given pharmaceuticals. SUBJECTS/METHODS: In this
study, medications of all the patients in a University Hospital with 1100 beds
were monitored to identify the appropriateness of administration. The study was
performed on 5 days each in 5 consecutive weeks to observe the current practice.
After evaluation of practice, a questionnaire was given to doctors, nurses and
pharmacists to determine the health-care professionals' attitudes on drug
administration through a feeding tube. RESULTS: A total of 225 drugs (out of 13
935) were administered via feeding tube during the study period and 40.5% (n=91)
were not administered in appropriate dosage forms. Only 86% of the doctors and
98% of the nurses stated that they pay attention to the suitability of drugs when
they prescribe or administer drugs via feeding tube. Only 58% of pharmacists, 17%
of nurses and 24% of doctors were aware of the fact that enteric-coated tablets
should not be crushed owing to the risk of tube occlusion and lack of efficacy
when they are administered via feeding tube. CONCLUSIONS: This study demonstrated
the discordance between the theoretical knowledge and the practical performance
of the health-care professionals in drug administration. In patients with feeding
tubes, assessment of drug dosage forms by a pharmacist would be beneficial for
appropriate administration and to prevent drug interactions.
PMID- 27507070
TI - Associations between body composition, physical capabilities and pulmonary
function in healthy older adults.
AB - BACKGROUND/OBJECTIVES: There are positive associations between pulmonary function
(PF) and fat-free mass as well as muscle strength. Contrarily, negative
associations were found with indirect measures of visceral adipose tissue (VAT).
We aimed to differentiate between associations of body composition and PF by
assessing mediating and moderating effects of physical capabilities.
SUBJECTS/METHODS: Cross-sectional data were assessed among 40 healthy, free
living elderly (20 males) aged 65.1-81.2 years (mean+/-s.d. age: 72.2+/-4.3
years; body mass index: 25.6+/-3.7 kg/m2). Total and regional skeletal muscle
(SM), and adipose tissue (AT) were measured using whole-body magnetic resonance
imaging. Muscle strength by handgrip dynamometry, physical activity (PA) by
questionnaire, and physical performance by gait speed and sit-to-stand test
(STS). Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)
were assessed by spirometry. RESULTS: Positive associations between height
standardized FVC (FVCI) as well as FEV1 (FEVI), and SM (r=0.435-0.520, P<0.05)
were found; subcutaneous AT (SAT) and FVCI correlated negatively (r=-0.374;
P<0.05). HGS and PA correlated positively with FEVI (r=0.456-0.608, P<0.05), HGS
also with FVCI (r=0.595, P<0.05). Stepwise multiple regression using FVCI and
FEVI as dependent variables, and total/thoracic SM, VAT, SAT, HGS, PA and
physical performance as independent variables showed that (i) only HGS entered
the regression for predicting FVCI (R2=0.351; standard error of estimation
(SEE)=0.32 l), and (ii) HGS and PA explained 50% of FEVI (SEE=0.23 l). HGS
mediated the relationship between SM and PF; the STS moderated the relationship
between SM and FVCI. CONCLUSIONS: In healthy elderly, PF is positively associated
with SM; physical capabilities mediate and moderate these relationships.
PMID- 27507071
TI - A tailored automated nutrition screening tool for rapid identification of risk in
acute-care hospital settings.
AB - Malnourishment is prevalent in hospitalized patients and associated with adverse
medical outcomes. Thus, nutrition screening to identify high-risk patients is
widespread. However, no single universal tool has been shown to be suitable for
all hospital departments. To address this challenge, a novel, tailored,
electronic tool for nutritional screening was developed and evaluated. The Rambam
Automated Nutrition Computerized Screening tool efficiently screens all newly
admitted patients and does not rely on self-reported height and weight estimates.
Validation was carried out in medical wards (n=94), and compared to the
Malnutrition Universal Screening Tool, length of stay and an independent
assessment by a professional dietician. Results from this research support the
use of automated, flexible tools that instantaneously incorporate relevant
available data from the electronic health record. Tools that are adaptable to
meet the needs of individual hospital departments, can save valuable time and
ensure full screening of all admitted patients.
PMID- 27507072
TI - The gluten-free basic food basket: a problem of availability, cost and
nutritional composition.
AB - The basic food basket (BFB), formed by the more economical products available, is
used by less-affluent countries to establish the minimum daily food consumption
to satisfy nutritional requirements in less-privileged individuals. There is no
information about groups that depend on the BFB and in addition follow gluten
free diet (GF/BFB). We measured availability, cost, main ingredients and
nutritional composition of GF/BFB. Data were collected in the area that was first
in the social priority list in the capital city, matching BFB components with
gluten-free equivalents (GF/BFB). GF/BFB characterized by being 42% less
available, three times more costly (>500% higher for bread), with up to 69% lower
protein content and with no fortifications, leaving at nutritional risk celiac
individuals that depend on GF/BFB. Results raise concerns on the capacity of the
GF/BFB to encourage adherence, maintain adequate nutritional status and quality
of life in celiac patients.
PMID- 27507073
TI - A Mediterranean-style diet, its components and the risk of heart failure: a
prospective population-based study in a non-Mediterranean country.
AB - BACKGROUND/OBJECTIVES: Growing evidence emerged about the role of diet in heart
failure (HF) development, but data are sparse and inconclusive. We examined the
association between a Mediterranean-style diet, its components and HF risk.
SUBJECTS/METHODS: Analyses were carried out in 24 008 middle-aged participants of
the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam
(Germany), including 209 incident HF cases within 8.2 years. The traditional
Greek Mediterranean diet score (tMED) was used to assess dietary adherence. Cox's
proportional hazards regression was applied to estimate the relationship between
the adherence to the Mediterranean-style diet, its components and HF risk.
RESULTS: After adjustment for age, sex and energy intake, a 2-unit increment in
the tMED was associated with 26% lower risk of HF (HR (95% confidence interval
(CI)): 0.76 (0.60-0.97)). After multivariable adjustment, this association was
slightly attenuated and lost significance [HR (95%CI): 0.82 (0.64-1.05)].
Interestingly, we observed a significant association in multivariable adjusted
models when milk products were excluded from the score (HR (95% CI): 0.75 (0.59
0.96)). Three score components were significantly associated with HF risk:
alcohol (HR (95%CI): 0.73 (0.55-0.97) for moderate versus low/high intakes),
meat: 2.04 (1.17-3.55) and fish: 0.59 (0.36-0.95), both for the highest versus
the lowest quintile. CONCLUSIONS: The tMED was not significantly associated with
HF risk, but low meat, high fish and moderate alcohol intake were inversely
associated with HF risk in our non-Mediterranean population. Minor dietary
changes could be valuable primary prevention measures, particularly the increase
of fish consumption while reducing the intake of meat.
PMID- 27507074
TI - Comparison of fatty acid intakes assessed by a cardiovascular-specific food
frequency questionnaire with red blood cell membrane fatty acids in
hyperlipidaemic Australian adults: a validation study.
AB - BACKGROUND/OBJECTIVES: Limited dietary intake tools have been validated
specifically for hyperlipidaemic adults. The Australian Eating Survey (AES) Food
Frequency Questionnaire (FFQ) was adapted to include foods with cardio-protective
properties (CVD-AES). The aims were to estimate dietary fatty acid (FA) intakes
derived from the CVD-AES and AES and compare them with red blood cell (RBC)
membrane FA content. SUBJECTS/METHODS: Dietary intake was measured using the semi
quantitative 120-item AES and 177-item CVD-AES. Nutrient intakes were calculated
using AUSNUT 2011-2013. Fasting RBC membrane FAs were assessed using gas
chromatography. Extent of agreement between intakes estimated by AES or CVD-AES
and RBC membrane composition (% of total FAs) for linoleic acid (LA), alpha
linolenic acid (ALA), eicosapentanoic acid (EPA), docosapentaenoic acid (DPA) and
docosahexaenoic acid (DHA) were assessed using Spearman's correlation
coefficients, adjusted linear regressions and Kappa statistics. RESULTS: Data
from 39 participants (72% female, 59.3+/-11.1 years) indicate stronger positive
correlations between RBC membrane FAs and CVD-AES dietary estimates compared with
the AES. Significant (P<0.05) moderate-strong correlations were found between CVD
AES FAs and FA proportions in RBC membranes for EPA (r=0.62), DHA (r=0.53) and
DPA (r=0.42), with a moderate correlation for LA (r=0.39) and no correlation with
ALA. Significant moderate correlations were found with the AES for DHA (r=0.39),
but not for LA, ALA, EPA or DPA. CONCLUSIONS: The CVD-AES provides a more
accurate estimate of long chain FA intakes in hyperlipidaemic adults, compared
with AES estimates. This indicates that a CVD-specific FFQ should be used when
evaluating FA intakes in this population.
PMID- 27507075
TI - Consumption of sugar-sweetened beverages and discretionary foods among US adults
by purchase location.
AB - BACKGROUND/OBJECTIVES: Excess calorie intake from sugar-sweetened beverages
(SSBs) and energy-dense, nutrient-poor foods occupies a significant proportion of
Western diet. The aim of this study was to examine consumption of SSBs and
discretionary foods in US adults by purchase location. SUBJECTS/METHODS:
Nationally representative 24-h dietary recall data came from the 2011-2012
National Health and Nutrition Examination Survey. The discretionary food category
identifies energy-dense, nutrient-poor foods that do not necessarily contain
essential nutrients but may add variety and enjoyment. Linear regressions were
performed to estimate daily calorie intake from SSBs and discretionary foods by
purchase location (supermarket/grocery store, convenience store, vending machine,
fast-food restaurant, full-service restaurant and other source), adjusting for
individual characteristics and sampling design. RESULTS: During 2011-2012, 46.3%
and 88.8% of US adults consumed SSBs and discretionary foods on any given day,
respectively. SSB consumers on average consumed 213.0 kcal from SSBs daily, of
which 111.6 kcal (52.4%) were purchased from supermarkets/grocery stores, 33.0
kcal (15.5%) from fast-food restaurants, 23.9 kcal (11.2%) from convenience
stores, 17.1 kcal (8.0%) from full-service restaurants, 8.5 kcal (4.0%) from
vending machines and 19.0 kcal (8.9%) from other sources. Discretionary food
consumers on average consumed 439.0 kcal from discretionary foods daily, of which
280.1 kcal (63.8%) were purchased from supermarkets/grocery stores, 45.8 kcal
(10.4%) from fast-food restaurants, 30.0 kcal (6.8%) from full-service
restaurants, 21.1 kcal (4.8%) from convenience stores, 4.1 kcal (0.9%) from
vending machines and 58.0 kcal (13.2%) from other sources. CONCLUSIONS:
Supermarkets/grocery stores were by far the single largest source for SSB and
discretionary food purchases in US adults.
PMID- 27507076
TI - A 7-day intravenous toxicity study and neurotoxicity assessment of pyridorin in
Sprague-Dawley rats.
AB - Pyridorin(r), a naturally occurring metabolite of vitamin B6 that inhibits and
scavenges reactive oxygen species, is being developed as a potential therapeutic
for acute kidney injury. An investigational new drug application (IND) was opened
for Pyridorin in support of its ongoing oral drug clinical development program.
Currently, a Pyridorin intravenous (IV) formulation is being developed for use in
surgical patients. To support the IND for Pyridorin, a full battery of
nonclinical Good Laboratory Practice compliant studies was performed with no
neurological or behavioral signs of toxicity seen following oral or IV
administration of pyridoxine dihydrochloride (the active ingredient in
Pyridorin). However, excessive ingestion of vitamin B6 has been reported to cause
neurotoxic syndrome in humans. Therefore, under Food and Drug Administration
recommendation, a 7-day IV study in rats was conducted to further evaluate the
drug's potential to cause neurotoxicity. Blood plasma samples indicated that
exposure to pyridoxamine dihydrochloride and its metabolites, pyridoxal,
pyridoxine, and 4-pyridoxic acid was linearly dose proportional and independent
of gender. At doses of up to 200 mg/kg/day pyridoxine dihydrochloride, no
treatment-related effects were seen in rats, providing further evidence for the
absence of pyridoxine dihydrochloride-related changes in the nervous system. A no
observed adverse effect level of 200 mg/kg/day was identified for this study.
PMID- 27507077
TI - Incorporating climate change into ecosystem service assessments and decisions: a
review.
AB - Climate change is having a significant impact on ecosystem services and is likely
to become increasingly important as this phenomenon intensifies. Future impacts
can be difficult to assess as they often involve long timescales, dynamic systems
with high uncertainties, and are typically confounded by other drivers of change.
Despite a growing literature on climate change impacts on ecosystem services, no
quantitative syntheses exist. Hence, we lack an overarching understanding of the
impacts of climate change, how they are being assessed, and the extent to which
other drivers, uncertainties, and decision making are incorporated. To address
this, we systematically reviewed the peer-reviewed literature that assesses
climate change impacts on ecosystem services at subglobal scales. We found that
the impact of climate change on most types of services was predominantly negative
(59% negative, 24% mixed, 4% neutral, 13% positive), but varied across services,
drivers, and assessment methods. Although uncertainty was usually incorporated,
there were substantial gaps in the sources of uncertainty included, along with
the methods used to incorporate them. We found that relatively few studies
integrated decision making, and even fewer studies aimed to identify solutions
that were robust to uncertainty. For management or policy to ensure the delivery
of ecosystem services, integrated approaches that incorporate multiple drivers of
change and account for multiple sources of uncertainty are needed. This is
undoubtedly a challenging task, but ignoring these complexities can result in
misleading assessments of the impacts of climate change, suboptimal management
outcomes, and the inefficient allocation of resources for climate adaptation.
PMID- 27507078
TI - When Will Physical Activity be Routinely Measured in the Clinical Setting? The
Case for Bariatric Surgery.
PMID- 27507079
TI - Response to "When will physical activity be routinely measured in the clinical
setting? The case for bariatric surgery".
PMID- 27507082
TI - Hypothyroidism and hyponatremia: data from a series of patients with iatrogenic
acute hypothyroidism undergoing radioactive iodine therapy after total
thyroidectomy for thyroid cancer.
AB - PURPOSE: The aim of the present study was to evaluate the role of hypothyroidism
as a cause of hyponatremia in a clinical model of iatrogenic acute hypothyroidism
due to thyroid hormone withdrawal prior to ablative radioactive iodine (RAI)
therapy after total thyroidectomy. METHODS: The study group consisted of 101
differentiated thyroid cancer (DTC) patients (77 women and 24 men). Plasma
concentration of thyroid-stimulating hormone ([TSH]) and sodium ([Na+]) was
evaluated before total thyroidectomy (pre[TSH] and pre[Na+]) and on the day of
RAI therapy (post[TSH] and post[Na+]). RESULTS: The frequency of hypothyroidism
associated hyponatremia was 4 % (4/101). Pre[Na+] was significantly higher than
post[Na+] (140.7 +/- 1.6 vs 138.7 +/- 2.3 mEq/L, p = 0.012). Moreover, a linear
correlation was identified between pre[Na+] and post[Na+]. CONCLUSIONS:
Iatrogenic acute hypothyroidism-related hyponatremia is uncommon. However,
because of the significant reduction of [Na+] in the transition from euthyroidism
to iatrogenic hypothyroidism, the value of pre[Na+] should be viewed as a
parameter to be considered. Since it acts as an independent risk factor for the
development of hyponatremia, patients with a pre[Na+] close to the lower limit of
normal range may deserve a closer monitoring of [Na+].
PMID- 27507083
TI - Experimental and DFT characterization, antioxidant and anticancer activities of a
Cu(II)-irbesartan complex: structure-antihypertensive activity relationships in
Cu(II)-sartan complexes.
AB - The coordination compound of the antihypertensive ligand irbesartan (irb) with
copper(II) (CuIrb) was synthesized and characterized by FTIR, FT-Raman, UV
visible, reflectance and EPR spectroscopies. Experimental evidence allowed the
implementation of structural and vibrational studies by theoretical calculations
made in the light of the density functional theory (DFT). This compound was
designed to induce structural modifications on the ligand. No antioxidant effects
were displayed by both compounds, though CuIrb behaved as a weak 1,1-diphenyl-2
picrylhydrazyl radical (DPPH(.)) scavenger (IC50 = 425 MUM). The measurements of
the contractile capacity on human mesangial cell lines showed that CuIrb improved
the antihypertensive effects of the parent medication. In vitro cell growth
inhibition against prostate cancer cell lines (LNCaP and DU 145) was measured for
CuIrb, irbesartan and copper(II). These cell lines have been selected since the
angiotensin II type 1 (AT1) receptor (that was blocked by the angiotensin
receptor blockers, ARB) has been identified in them. The complex exerted
anticancer behavior (at 100 MUM) improving the activity of the ligand. Flow
cytometry determinations were used to determine late apoptotic mechanisms of cell
death. Experimental and DFT characterization of an irbesartan copper(II) complex
has been performed. The complex exhibits low scavenging activity against DPPH(.)
and significant growth inhibition of LNCaP and DU 145 prostate cancer cell lines.
Flow cytometry determinations were used to determine late apoptotic mechanisms of
cell death. This compound improved the antihypertensive effect of irbesartan.
This effect was observed earlier for the mononuclear Cu-candesartan complex, but
not in structurally modified sartans forming dinuclear or octanuclear Cu-sartan
compounds.
PMID- 27507084
TI - The association between particulate air pollution and respiratory admissions
among young children in Hanoi, Vietnam.
AB - While the effects of ambient air pollution on health have been studied
extensively in many developed countries, few studies have been conducted in
Vietnam, where the population is exposed to high levels of airborne particulate
matter. The aim of our study was to examine the short-term effects of PM10,
PM2.5, and PM1 on respiratory admissions among young children in Hanoi. Data on
daily admissions from the Vietnam National Hospital of Paediatrics and daily
records of PM10, PM2.5, PM1 and other confounding factors as NO2, SO2, CO, O3 and
temperature were collected from September 2010 to September 2011. A time
stratified case-crossover design with individual lag model was applied to
evaluate the associations between particulate air pollution and respiratory
admissions. Significant effects on daily hospital admissions for respiratory
disease were found for PM10, PM2.5 and PM1. An increase in 10MUg/m3 of PM10,
PM2.5 or PM1 was associated with an increase in risk of admission of 1.4%, 2.2%
or 2.5% on the same day of exposure, respectively. No significant difference
between the effects on males and females was found in the study. The study
demonstrated that infants and young children in Hanoi are at increased risk of
respiratory admissions due to the high level of airborne particles in the city's
ambient air.
PMID- 27507085
TI - A tool box strategy using Bacteroides genetic markers to differentiate human from
non-human sources of fecal contamination in natural water.
AB - Bacteroides genetic markers have been widely used to identify fecal pollution of
water originating from human and animal sources. Many of the assays currently
used for detecting human-specific Bacteroides produce false positive results. The
focus of this study was to develop a microbial source tracking (MST) tool box
strategy for differentiating Bacteroides from human and animal sources.
Bacteroides 16S rRNA gene sequences from fish and selected animals were aligned
against human fecal Bacteroides isolates to compare and characterize the variable
regions within the 16S rRNA gene sequence. Conserved sequences between 4 variable
regions were deleted and the truncated sequences were combined to develop a hyper
variable genomic segment (HVGS). The cladogram created from truncated sequences
show a clear separation of Bacteroides from human feces and those from animal
sources. The proposed strategy was field tested by collecting water samples from
central Arizona source waters and three different recreational ponds. PCR using
HF134 and HF183 primer sets was performed and sequences from positive reactions
were aligned against human Bacteroides sequences to identify the source of
contamination. Based on PCR results, the source of fecal contamination was
presumptively identified as either human or from another source. For samples
testing positive using the HF183 primer set (8/13), fecal contamination was
presumed to be from human sources, but to confirm the results, PCR products were
sequenced and aligned against the four variable regions and then incorporated
within the truncated cladogram. As expected, the sequences from water samples
with human fecal contamination grouped in a separate clade. A variability matrix,
developed after exclusion of conserved sequences among the four regions, was
utilized to establish discrete groupings for sequences within the truncated
cladogram, generally differentiating Bacteroides isolates from varying host
animals, but most importantly, separating Bacteroides from human feces from
Bacteroides from other animals. The proposed strategy offers a new tool box
method for MST and a step-wise methodology essential for identifying human
sources of fecal pollution.
PMID- 27507086
TI - Phosphorus in the catchment of high sediment load river: A case of the Yellow
River, China.
AB - Surface sediment samples concurrently collected in the catchment of the Ningxia
Inner Mongolian reach of Yellow River (NIMYR) were analyzed to determine the
phosphorus and correlated physiochemical properties of sediments. Samples were
obtained from three main areas: the riverbed surface sediment (RSS), the
floodplain surface sediment (FSS) and the desert surface sediment (DSS). The
sequence of phosphorus-contamination level in this catchment, determined by a
cumulative distribution function and multivariate statistical analysis, were
FSS>RSS>DSS. Moreover, because of the impacts of anthropogenic activities, the
sampling site with the highest and lowest phosphorus concentration (mgkg-1) of
this catchment appeared in RSS (749.40) and DSS (200.10) respectively. In
addition, this is the first study to present a qualification of the effect of the
sediment's physicochemical properties on phosphorus by the multivariate
regression tree analysis. Co-precipitation of phosphate with calcite [i],
phosphate absorbed onto ferric hydroxides [ii] and grain-size effect [iii] were
the three main mechanisms for phosphorus distribution in the sediment of NIMYR.
The contributions of these three mechanisms to RSS and FSS were, respectively,
[i]>[iii]>[ii] and [i]>[ii]>[iii]. The heaviest phosphorus-contaminated group of
RSS was primarily controlled by [i], whereas the heaviest phosphorus-contaminated
group of FSS was controlled by [i] and [ii], indicating that the FSS had a higher
potential risk of releasing phosphorus from the sediment to overlying water.
PMID- 27507087
TI - Enhancing microbial production of biofuels by expanding microbial metabolic
pathways.
AB - Fatty acid, isoprenoid, and alcohol pathways have been successfully engineered to
produce biofuels. By introducing three genes, atfA, adhE, and pdc, into
Escherichia coli to expand fatty acid pathway, up to 1.28 g/L of fatty acid ethyl
esters can be achieved. The isoprenoid pathway can be expanded to produce
bisabolene with a high titer of 900 mg/L in Saccharomyces cerevisiae. Short- and
long-chain alcohols can also be effectively biosynthesized by extending the
carbon chain of ketoacids with an engineered "+1" alcohol pathway. Thus, it can
be concluded that expanding microbial metabolic pathways has enormous potential
for enhancing microbial production of biofuels for future industrial
applications. However, some major challenges for microbial production of biofuels
should be overcome to compete with traditional fossil fuels: lowering production
costs, reducing the time required to construct genetic elements and to increase
their predictability and reliability, and creating reusable parts with useful and
predictable behavior. To address these challenges, several aspects should be
further considered in future: mining and transformation of genetic elements
related to metabolic pathways, assembling biofuel elements and coordinating their
functions, enhancing the tolerance of host cells to biofuels, and creating
modular subpathways that can be easily interconnected.
PMID- 27507088
TI - Analysis of high-order SNP barcodes in mitochondrial D-loop for chronic dialysis
susceptibility.
AB - OBJECTIVES: Positively identifying disease-associated single nucleotide
polymorphism (SNP) markers in genome-wide studies entails the complex association
analysis of a huge number of SNPs. Such large numbers of SNP barcode
(SNP/genotype combinations) continue to pose serious computational challenges,
especially for high-dimensional data. METHODS: We propose a novel exploiting SNP
barcode method based on differential evolution, termed IDE (improved differential
evolution). IDE uses a "top combination strategy" to improve the ability of
differential evolution to explore high-order SNP barcodes in high-dimensional
data. RESULTS: We simulate disease data and use real chronic dialysis data to
test four global optimization algorithms. In 48 simulated disease models, we show
that IDE outperforms existing global optimization algorithms in terms of
exploring ability and power to detect the specific SNP/genotype combinations with
a maximum difference between cases and controls. In real data, we show that IDE
can be used to evaluate the relative effects of each individual SNP on disease
susceptibility. CONCLUSION: IDE generated significant SNP barcode with less
computational complexity than the other algorithms, making IDE ideally suited for
analysis of high-order SNP barcodes.
PMID- 27507089
TI - Correlation between videogame mechanics and executive functions through EEG
analysis.
AB - This paper addresses a different point of view of videogames, specifically
serious games for health. This paper contributes to that area with a
multidisciplinary perspective focus on neurosciences and computation. The
experiment population has been pre-adolescents between the ages of 8 and 12
without any cognitive issues. The experiment consisted in users playing
videogames as well as performing traditional psychological assessments; during
these tasks the frontal brain activity was evaluated. The main goal was to
analyse how the frontal lobe of the brain (executive function) works in terms of
prominent cognitive skills during five types of game mechanics widely used in
commercial videogames. The analysis was made by collecting brain signals during
the two phases of the experiment, where the signals were analysed with an
electroencephalogram neuroheadset. The validated hypotheses were whether
videogames can develop executive functioning and if it was possible to identify
which kind of cognitive skills are developed during each kind of typical
videogame mechanic. The results contribute to the design of serious games for
health purposes on a conceptual level, particularly in support of the diagnosis
and treatment of cognitive-related pathologies.
PMID- 27507090
TI - Automated population of an i2b2 clinical data warehouse from an openEHR-based
data repository.
AB - BACKGROUND: Detailed Clinical Model (DCM) approaches have recently seen wider
adoption. More specifically, openEHR-based application systems are now used in
production in several countries, serving diverse fields of application such as
health information exchange, clinical registries and electronic medical record
systems. However, approaches to efficiently provide openEHR data to researchers
for secondary use have not yet been investigated or established. METHODS: We
developed an approach to automatically load openEHR data instances into the open
source clinical data warehouse i2b2. We evaluated query capabilities and the
performance of this approach in the context of the Hanover Medical School
Translational Research Framework (HaMSTR), an openEHR-based data repository.
RESULTS: Automated creation of i2b2 ontologies from archetypes and templates and
the integration of openEHR data instances from 903 patients of a paediatric
intensive care unit has been achieved. In total, it took an average of ~2527s to
create 2.311.624 facts from 141.917 XML documents. Using the imported data, we
conducted sample queries to compare the performance with two openEHR systems and
to investigate if this representation of data is feasible to support cohort
identification and record level data extraction. DISCUSSION: We found the
automated population of an i2b2 clinical data warehouse to be a feasible approach
to make openEHR data instances available for secondary use. Such an approach can
facilitate timely provision of clinical data to researchers. It complements
analytics based on the Archetype Query Language by allowing querying on both,
legacy clinical data sources and openEHR data instances at the same time and by
providing an easy-to-use query interface. However, due to different levels of
expressiveness in the data models, not all semantics could be preserved during
the ETL process.
PMID- 27507097
TI - Structural basis of unique ligand specificity of KAI2-like protein from parasitic
weed Striga hermonthica.
AB - The perception of two plant germination inducers, karrikins and strigolactones,
are mediated by the proteins KAI2 and D14. Recently, KAI2-type proteins from
parasitic weeds, which are possibly related to seed germination induced by
strigolactone, have been classified into three clades characterized by different
responses to karrikin/strigolactone. Here we characterized a karrikin-binding
protein in Striga (ShKAI2iB) that belongs to intermediate-evolving KAI2 and
provided the structural bases for its karrikin-binding specificity. Binding
assays showed that ShKAI2iB bound karrikins but not strigolactone, differing from
other KAI2 and D14. The crystal structures of ShKAI2iB and ShKAI2iB-karrikin
complex revealed obvious structural differences in a helix located at the entry
of its ligand-binding cavity. This results in a smaller closed pocket, which is
also the major cause of ShKAI2iB's specificity of binding karrikin. Our
structural study also revealed that a few non-conserved amino acids led to the
distinct ligand-binding profile of ShKAI2iB, suggesting that the evolution of
KAI2 resulted in its diverse functions.
PMID- 27507099
TI - A genomic view of the peopling of the Americas.
AB - Whole-genome studies have documented that most Native American ancestry stems
from a single population that diversified within the continent more than twelve
thousand years ago. However, this shared ancestry hides a more complex history
whereby at least four distinct streams of Eurasian migration have contributed to
present-day and prehistoric Native American populations. Whole genome studies
enhanced by technological breakthroughs in ancient DNA now provide evidence of a
sequence of events involving initial migrations from a structured Northeast Asian
source population with differential relatedness to present-day Australasian
populations, followed by a divergence into northern and southern Native American
lineages. During the Holocene, new migrations from Asia introduced the
Saqqaq/Dorset Paleoeskimo population to the North American Arctic ~4500 years
ago, ancestry that is potentially connected with ancestry found in Athabaskan
speakers today. This was then followed by a major new population turnover in the
high Arctic involving Thule-related peoples who are the ancestors of present-day
Inuit. We highlight several open questions that could be addressed through future
genomic research.
PMID- 27507098
TI - Insights into human evolution from ancient and contemporary microbiome studies.
AB - Over the past decade, human microbiome research has energized the study of human
evolution through a complete shift in our understanding of what it means to be
human. The microbiome plays a pivotal role in human biology, performing key
functions in digestion, mood and behavior, development and immunity, and a range
of acute and chronic diseases. It is therefore critical to understand its
evolution and changing ecology through time. Here we review recent findings on
the microbiota of diverse human populations, non-human primates, and past human
populations and discuss the implications of this research in formulating a deeper
evolutionary understanding of the human holobiont.
PMID- 27507100
TI - Biomimetic nucleus pulposus scaffold created from bovine caudal intervertebral
disc tissue utilizing an optimal decellularization procedure.
AB - Intervertebral disc (IVD) degeneration (IDD) and herniation (IDH) can result in
low back pain and impart significant socioeconomic burden. These pathologies
involve detrimental alteration to the nucleus pulposus (NP) either via
biochemical degradation or extrusion from the IVD, respectively. Thus,
engineering living NP tissue utilizing biomaterial scaffolds that recapitulate
native NP microarchitecture, biochemistry, mechanical properties, and which
support cell viability represents an approach to aiding patients with IDD and
IDH. To date, an ideal biomaterial to support NP regeneration has yet to be
developed; however, one promising approach to generating biomimetic materials is
to employ the decellularization (decell) of xenogeneic NP tissue to remove host
DNA while maintaining critical native extracellular matrix (ECM) components.
Herein, 13 different procedures were evaluated in an attempt to decell bovine
caudal IVD NP tissue. An optimal method was identified which was confirmed to
effectively remove bovine DNA, while maintaining physiologically relevant amounts
of glycosaminoglycan (GAG) and type II collagen. Unconfined static and dynamic
compressive mechanical properties of scaffolds approached values reported for
human NP and viability of human amniotic stem cells (hAMSCs) was maintained on
noncrosslinked and EDC/NHS treated scaffolds for up to 14 days in culture. Taken
together, NP tissue obtained from bovine caudal IVDs can be successfully decelled
in order to generate a biomimetic scaffold for NP tissue regeneration. (c) 2016
Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3093-3106, 2016.
PMID- 27507101
TI - Novel ligands of Choline Acetyltransferase designed by in silico molecular
docking, hologram QSAR and lead optimization.
AB - Recent reports have brought back the acetylcholine synthesizing enzyme, choline
acetyltransferase in the mainstream research in dementia and the cholinergic anti
inflammatory pathway. Here we report, a specific strategy for the design of novel
ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity
Relationship (HQSAR) and lead optimization. Molecular docking was performed on a
series of ChAT inhibitors to decipher the molecular fingerprint of their
interaction with the active site of ChAT. Then robust statistical fragment HQSAR
models were developed. A library of novel ligands was generated based on the
pharmacophoric and shape similarity scoring function, and evaluated in silico for
their molecular interactions with ChAT. Ten of the top scoring invented compounds
are reported here. We confirmed the activity of alpha-NETA, the only commercially
available ChAT inhibitor, and one of the seed compounds in our model, using a new
simple colorimetric ChAT assay (IC50 ~ 88 nM). In contrast, alpha-NETA exhibited
an IC50 of ~30 MUM for the ACh-degrading cholinesterases. In conclusion, the
overall results may provide useful insight for discovering novel ChAT ligands and
potential positron emission tomography tracers as in vivo functional biomarkers
of the health of central cholinergic system in neurodegenerative disorders, such
as Alzheimer's disease.
PMID- 27507102
TI - Gut microbiota: D-amino acids employed against gut pathogens.
PMID- 27507103
TI - IBD: A timely diagnosis of primary sclerosing cholangitis in IBD.
PMID- 27507105
TI - Left-Sided Catamenial Pneumothorax with Thoracic Endometriosis and Bullae in the
Alveolar Wall.
AB - Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking
from the uterus into the thoracic cavity via a defect in the endometrial tissue
of the diaphragm and is usually detected in the right thorax. We report a case of
left-sided CP caused by endometriosis in the visceral pleura and with no abnormal
findings in the diaphragm. A 33-year-old female patient presented at the end of a
course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous
pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung
lobe. The patient underwent partial resection of the lung. Immunohistochemistry
confirmed the presence of endometrial stromal tissue in the visceral pleura and
confirmed this as the cause of pneumothorax since there were no observable
abnormalities in the diaphragm. This case suggests that immunohistochemical
examination of patients with spontaneous pneumothorax can detect alternative
endometrial lesions.
PMID- 27507106
TI - Long-Term Quality of Life after Cardiac and Thoracic Aortic Surgery for Very
Elderly Patients 85 Years or Older.
AB - PURPOSE: We evaluated the outcomes of open heart surgery and long-term quality of
life for patients 85 years and older. METHODS: We enrolled 46 patients 85 years
and older who underwent cardiac and thoracic aortic surgery between May 1999 and
November 2012. Long-term assessment was performed for 43 patients; three patients
who died in the hospital were excluded. Patient conditions were assessed before
surgery, 6 months and 12 months after surgery, and during the late period
regarding the need for nursing care, degree of independent living, and living
willingness. RESULTS: Three patients (6.5%) died during hospitalization and 22
(51%) died during the follow-up period. The 1-, 3-, 5-year survival rates were
74%, 49%, and 36%. During the late period, of 21 surviving patients, 18 patients
(85%) were living at home. The need for nursing care was comparable before and
after surgery. The degree of independent living decreased after surgery. Living
willingness was similar before and after surgery. CONCLUSION: Among patients 85
years or older who underwent open heart surgery, 85% were living at home. All
patients could perform activities of daily living without any assistance while
maintaining living willingness.
PMID- 27507104
TI - Bioengineering the gut: future prospects of regenerative medicine.
AB - Functions of the gastrointestinal tract include motility, digestion and
absorption of nutrients. These functions are mediated by several specialized cell
types including smooth muscle cells, neurons, interstitial cells and epithelial
cells. In gastrointestinal diseases, some of the cells become degenerated or fail
to accomplish their normal functions. Surgical resection of the diseased segments
of the gastrointestinal tract is considered the gold-standard treatment in many
cases, but patients might have surgical complications and quality of life can
remain low. Tissue engineering and regenerative medicine aim to restore, repair,
or regenerate the function of the tissues. Gastrointestinal tissue engineering is
a challenging process given the specific phenotype and alignment of each cell
type that colonizes the tract - these properties are critical for proper
functionality. In this Review, we summarize advances in the field of
gastrointestinal tissue engineering and regenerative medicine. Although the
findings are promising, additional studies and optimizations are needed for
translational purposes.
PMID- 27507107
TI - Lymph Node Dissection in Surgery for Lung Cancer: Comparison of Open vs. Video
Assisted vs. Robotic-Assisted Approaches.
AB - PURPOSE: We compared open, video-assisted and robotic-assisted thoracoscopic
surgical techniques in the dissection of N1 and N2-level lymph nodes during
surgery for lung cancer. METHODS: This retrospective analysis is based on
prospectively collected data of patients (excluding those with N2 or N3 diseases,
and sleeve resections) undergoing mediastinal lymph node dissection via open (n =
96), video-assisted thoracoscopy (n = 68), and robotic-assisted thoracoscopy (n =
106). The groups are compared according to the number of lymph node stations
dissected, the number of lymph nodes dissected, and the number of lymph nodes
dissected by stations. RESULTS: Three techniques had similar results based on the
number of the dissected N1 and N2-level lymph node stations. Robotic-assisted
thoracoscopic surgery yielded significantly more lymph nodes in total (p =
0.0007), and in the number of dissected N1-level nodes (p <0.0001). All
techniques yielded similar number of mediastinal lymph nodes, whereas robotic
assisted thoracic surgery (RATS) yielded more station #11 and #12 lymph nodes
compared to the other groups. CONCLUSIONS: In this study, robotic-assisted
thoracoscopic surgery has been shown to dissect more lymph nodes at N1 level.
However, taking the open approach as standard, we could claim that both currently
robotic and video-assisted techniques may provide similar number of dissected N1
and N2-level lymph node stations.
PMID- 27507108
TI - Role of phytochemicals in the inhibition of epithelial-mesenchymal transition in
cancer metastasis.
AB - Epithelial-mesenchymal transition (EMT) is the process by which epithelial cells
become mesenchymal cells, gaining fibroblast-like properties and displaying
reduced intercellular adhesion and increased motility. EMT plays an important
role in cancer metastasis. Suppressing or reversing EMT is therefore an important
way of controlling various cancers. Phytochemicals are important sources of
anticancer lead molecules. Natural products have been shown to safely suppress or
reverse EMT via the inhibition of associated signalling pathways in various
cancer cells. In the present review, we discuss the relevant factors and the role
of EMT in cancer metastasis. We then present examples of phytochemicals with a
role in the inhibition and reversal of EMT in various cancers, focusing on
reports from 2012 to 2016.
PMID- 27507109
TI - Design, synthesis and biological evaluation of novel hamamelitannin analogues as
potentiators for vancomycin in the treatment of biofilm related Staphylococcus
aureus infections.
AB - Staphylococcus aureus is a frequent cause of biofilm-related infections.
Bacterial cells within a biofilm are protected from attack by the immune system
and conventional antibiotics often fail to penetrate the biofilm matrix. The
discovery of hamamelitannin as a potentiator for antibiotics, recently led to the
design of a more drug-like lead. In the present study, we want to gain further
insight into the structure-activity relationship (S.A.R.) of the 5-position of
the molecule, by preparing a library of 21 hamamelitannin analogues.
PMID- 27507110
TI - Discovery of a new type of scaffold for the creation of novel tyrosinase
inhibitors.
AB - Tyrosinase is known as the key enzyme for melanin biosynthesis, which is
effective in preventing skin injury by ultra violet (UV). In past decades,
tyrosinase has been well studied in the field of cosmetics, medicine, agriculture
and environmental sciences, and a lot of tyrosinase inhibitors have been
developed for their needs. Here, we searched for new types of tyrosinase
inhibitors and found phenylbenzoic acid (PBA) as a unique scaffold. Among three
isomers of PBA, 3-phenylbenzoic acid (3-PBA) was revealed to be the most potent
inhibitor against mushroom tyrosinase (IC50=6.97MUM, monophenolase activity;
IC50=36.3MUM, diphenolase activity). The kinetic studies suggested that the
apparent inhibition modes for the monophenolase and diphenolase activities were
noncompetitive and mixed type inhibition, respectively. Analyses by in silico
docking studies using the crystallographic structure of mushroom tyrosinase
indicated that the carboxylic acid group of the 3-PBA could adequately bind to
two cupric ions in the tyrosinase. To prove this hypothesis, we examined the
effect of modification of the carboxylic acid group of the 3-PBA on its
inhibitory activity. As expected, the esterification abrogated the inhibitory
activity. These observations suggest that 3-PBA is a useful lead compound for the
generation of novel tyrosinase inhibitors and provides a new insight into the
molecular basis of tyrosinase catalytic mechanisms.
PMID- 27507111
TI - Frequency of Poor Outcome (Death or Poor Quality of Life) After Left Ventricular
Assist Device for Destination Therapy: Results From the INTERMACS Registry.
AB - BACKGROUND: A left ventricular assist device (LVAD) improves survival and quality
of life for many, but not all, patients with end-stage heart failure who are
ineligible for transplantation. We sought to evaluate the frequency of poor
outcomes using a novel composite measure that integrates quality of life with
mortality. METHODS AND RESULTS: Within the INTERMACS (Interagency Registry for
Mechanically Assisted Circulatory Support) national registry, poor outcome was
defined as death or an average Kansas City Cardiomyopathy Questionnaire <45
during the year after LVAD (persistently limiting heart failure symptoms and poor
quality of life). Among 1638 patients with LVAD, 29.7% had a poor outcome, with
death in 22.4% and persistently poor quality of life in 7.3%. Patients who had a
poor outcome were more likely to have higher body mass indices (29.3 versus 28.2
kg/m(2); P=0.007), lower hemoglobin levels (11.1 versus 11.4 g/dL; P=0.005),
previous cardiac surgery (47.8% versus 39.8%; P=0.004), history of cancer (13.8%
versus 9.7%; P=0.025), severe diabetes mellitus (15.6% versus 11.5%; P=0.038),
and poorer quality of life preimplant (Kansas City Cardiomyopathy Questionnaire
scores: 29.8 versus 35.3; P<0.001). CONCLUSIONS: Nearly one third of patients die
or have a persistently poor quality of life during the year after LVAD. We
identified several factors associated with a poor outcome, which may inform
discussions before LVAD implantation to enable more realistic expectations of
recovery.
PMID- 27507112
TI - Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute Heart
Failure.
AB - BACKGROUND: Chloride plays a role in renal salt sensing, neurohormonal
activation, and regulation of diuretic targets, and hypochloremia predicts
mortality in acute heart failure (AHF). AHF therapies, such as diuretics, alter
chloride homeostasis. We studied the association between (changes in) chloride
levels and diuretic responsiveness, decongestion, and mortality in patients with
AHF. METHODS AND RESULTS: Patients hospitalized for AHF in the PROTECT trial
(n=2033) with serum chloride levels within 24 hours of admission and 14 days
later were studied (n=1960). Hypochloremia was defined as serum chloride <96
mEq/L. Mean baseline chloride was 100.8+/-5.0 mEq/L. Low baseline chloride was
associated with high bicarbonate, poor diuretic response, less hemoconcentration,
and worsening heart failure (all P<0.01). Newly developed hypochloremia at day 14
was common and associated with a decline in renal function and an increase in
blood urea nitrogen (P<0.01). In multivariable analyses, chloride measured at day
14, but not baseline chloride, was strongly and independently associated with
mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03-1.10];
P<0.001). In comparison, sodium was not significantly associated with mortality
after multivariable adjustment at any time point. Hypochloremia at baseline that
resolved was not associated with mortality (P=0.55), but new or persistent
hypochloremia at day 14 was associated with increased mortality (hazard ratio:
3.11 [2.17-4.46]; P<0.001). CONCLUSIONS: Low serum chloride at AHF hospital
admission was strongly associated with impaired decongestion. New or persistent
hypochloremia 14 days later was independently associated with reduced survival,
whereas hypochloremia that resolved by day 14 was not. CLINICAL TRIAL
REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354458.
PMID- 27507114
TI - Putting Life in the Years: Incorporating Quality of Life Into Left Ventricular
Assist Devices Outcomes.
PMID- 27507113
TI - Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights.
AB - BACKGROUND: Recent epidemiological studies have implicated chloride, rather than
sodium, as the driver of poor survival previously attributed to hyponatremia in
heart failure. Accumulating basic science evidence has identified chloride as a
critical factor in renal salt sensing. Our goal was to probe the physiology
bridging this basic and epidemiological literature. METHODS AND RESULTS: Two
heart failure cohorts were included: (1) observational: patients receiving loop
diuretics at the Yale Transitional Care Center (N=162) and (2) interventional
pilot: stable outpatients receiving >=80 mg furosemide equivalents were studied
before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the
Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride <=96
mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46;
P<0.001) with no incremental contribution from serum sodium (P=0.49).
Hypochloremic versus nonhypochloremic patients exhibited renal wasting of
chloride (P=0.04) and of chloride relative to sodium (P=0.01), despite better
renal free water excretion (urine osmolality 343+/-101 mOsm/kg versus 475+/-136;
P<0.001). Hypochloremia was associated with poor diuretic response (odds ratio,
7.3; 95% confidence interval, 3.3-16.1; P<0.001). In the interventional pilot,
lysine chloride supplementation was associated with an increase in serum chloride
levels of 2.2+/-2.3 mmol/L, and the majority of participants experienced findings
such as hemoconcentration, weight loss, reduction in amino terminal, pro B-type
natriuretic peptide, increased plasma renin activity, and increased blood urea
nitrogen to creatinine ratio. CONCLUSIONS: Hypochloremia is associated with
neurohormonal activation and diuretic resistance with chloride depletion as a
candidate mechanism. Sodium-free chloride supplementation was associated with
increases in serum chloride and changes in several cardiorenal parameters.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT02031354.
PMID- 27507115
TI - Endoluminal application of glass-capped diffuser for ex vivo endovenous
photocoagulation.
AB - Endovenous laser ablation (EVLA) has frequently been used to treat varicose veins
for 20 years. In spite of 90~95% occlusion rates, clinical complications such as
burn and ecchymosis still occur due to excessive thermal injury to perivenous
tissue. In the current study, a glass-capped diffusing applicator is designed to
validate the feasibility of EVLA as an effective therapeutic device by applying
circumferential light distribution. The proposed device is evaluated with a flat
fiber as a reference in terms of temperature elevation, fiber degradation, and
degree of coagulative necrosis after 532 nm-assisted EVLA at 100 J/cm. The
diffusing fiber generates a 40% lower maximum temperature with a 90% lower
transient temperature change in blood, compared to the flat fiber. Due to low
irradiance (13.5 kW/cm2 ) and wide light distribution, the diffuser tip
experiences no significant thermal degradation while severe carbonization occurs
at the flat fiber tip. Ex vivo tissue tests verify that the diffusing fiber
induces circumferential and consistent tissue denaturation to the vein wall
(107.8 +/- 7.8 um) along with 19% vessel shrinkage. The proposed glass-capped
diffusing applicator can be a feasible therapeutic device for EVLA with minimal
complications by entailing low maximum temperatures and uniform tissue
denaturation in the venous tissue.
PMID- 27507116
TI - Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia
reperfusion injuries in isolated rabbit heart.
AB - Restoration of blood flow to the ischemic myocardium is imperative to avoid
demise of cardiomyocytes, but is paradoxically associated with irreversible
damage to cardiac tissues due to the excessive generation of reactive oxygen
species (ROS). We have previously reported that saffron, a natural antioxidant,
attenuated ischemia-reperfusion (IR) injuries in vitro; however, its role in a
meaningful cardiac recovery remains unknown. Here, we show that saffron
supplement (oral administration for 6 weeks) reduced myocardial damage and
restored cardiac function in an IR model of rabbit hearts. This was evidenced by
improved left ventricle pressure, heart rate and coronary flow, and left
ventricle end diastolic pressure (LVEDP) in IR hearts (isolated from rabbits pre
exposed to saffron (S/IR)). Electrophysiological recordings revealed a
significant decline in both premature ventricle contraction and ventricle
tachycardia/fibrillation in S/IR compared to IR hearts. This was paralleled by
increased expression of the contractile proteins alpha-actinin and Troponin C in
the myocardium of S/IR hearts. Histological examination combined to biochemical
analysis indicated that hearts pre-exposed to saffron exhibited reduced infarct
size, lower lipid peroxidation, with increased glutathione peroxidase activity,
and oxidation of nitro blue tetrazolium (by reactive oxygen species).
Furthermore, in contrast with IR hearts, saffron pretreatment induced restoration
of the phosphorylation level of the survival proteins Akt and 4EBP1 and reduced
activity of p38. Collectively, our data demonstrate that the natural antioxidant
saffron plays a pivotal role in halting IR-associated cardiac injuries and
emerges as a novel preventive tool for ischemic heart disease.
PMID- 27507117
TI - Fluorescent cyanine dyes for the quantification of low amounts of dsDNA.
AB - In this research six cyanine fluorophores for the quantification of dsDNA in the
pg-ng range, without amplification, are compared under exactly identical
conditions: EvaGreen, SYBR Green, PicoGreen, AccuClear, AccuBlue NextGen and YOYO
1. The fluorescence intensity as a function of the amount of dsDNA is measured at
the optimal wavelengths for excitation and emission and for each dye the limit of
detection and the response linearity at low levels of dsDNA are determined. No
linear range was found for SYBR Green and YOYO-1 for pg-ng quantities of dsDNA.
EvaGreen, PicoGreen, AccuClear and AccuBlue NextGen show good linearity in the pg
ng range. AccuClear exhibits the widest linear range of 3 pg-200 ng, whereas
AccuBlue NextGen turned out to have the highest sensitivity of the tested dyes
with a limit of detection of 50 pg.
PMID- 27507118
TI - Payer Formulary Alerts as a Cause of Patient Harm and the Journey to Change Them.
AB - BACKGROUND AND OBJECTIVES: A safety event drew attention to unsafe and
inappropriate payer formulary alerts. These alerts display formulary, coverage,
and eligibility data from the pharmacy benefits manager in response to an
electronic prescription. They are intended to redirect prescribers to medications
that are covered by insurance; however, these alerts were found to be inaccurate
and contribute to potentially harmful alerts. Our objective was to reduce
inappropriate payer formulary alerts by 30% within 1 year and to change the
ePrescribing certification requirements to prevent future instances of harm.
METHODS: Using process mapping we identified the changes that were required both
locally and nationally through our electronic health record (EHR) vendor and
ePrescribing transaction broker. We partnered with vendors to show the safety
risk and to suggest modifications to the payer formulary alert content and
ePrescribing certification criteria. On the basis of the new criteria, we
modified and deactivated inappropriate alerts. Rates were followed weekly for 13
months and a control chart was used to track progress. RESULTS: From January 2014
to January 2015, we reviewed 59 325 payer formulary alerts from ambulatory care
and 11 630 from the emergency department and inpatient wards. Both local and
national modifications resulted in significant and sustained decreases in
inappropriate alerts. CONCLUSIONS: Enduring and meaningful change required
partnership with multiple stakeholders, including EHR vendors, ePrescribing
vendors, and pharmacy benefits managers. Improving drug alerts, reducing alert
fatigue, and promoting value-based prescribing in the EHR will likely require
similar partnerships.
PMID- 27507119
TI - Coarse and fine N1 tuning for print in younger and older Chinese children:
Orthography, phonology, or semantics driven?
AB - Visual expertise in distinguishing words from objects and word-like stimuli is a
fundamental skill that is important for children to become proficient readers.
This expertise can be indexed by the N1 component of ERPs at the neural level.
However, the nature of N1 tuning for print is controversial in terms of onset of
the latency, lateralization and the neural mechanism of the N1. This study aimed
to investigate whether two groups of Chinese children could discriminate
characters/character-like stimuli from visual controls (i.e., coarse N1 tuning)
and distinguish characters from character-like stimuli (i.e., fine N1 tuning). We
also explored the cognitive-linguistic correlates of N1 tuning. Seventeen
children in the younger group (M=7.7 years) and 13 in the older group (M=9.4
years) were all required to finish a character decision task with character,
pseudocharacter, noncharacter, and stroke combination conditions using ERP
testing. Both the pseudocharacters and noncharacters were unpronounceable, and
the main difference between the two conditions was in orthographic presentation
(i.e., radical position). Children were also administered measures of reading
fluency, reading accuracy, RAN, phonological skill and vocabulary knowledge. ERP
results showed that a significantly larger N1 was observed in the characters,
pseudocharacters, and noncharacters as compared to the stroke combinations in
both groups. The N1 for characters and pseudocharacters was also significantly
larger than that for noncharacters in both groups. Both coarse and fine N1s were
larger for younger children than for older children, and the N1 was bilateral in
younger children, but left lateralized in older children. Correlational analyses
showed that the coarse N1 tuning of real characters versus visual controls was
moderately correlated with reading fluency and accuracy but not RAN, phonology,
or vocabulary. Taken together, our study suggests that both coarse and fine N1
tuning occurs in both younger and older children, when performing character
decisions. Under such task demands, orthography, rather than phonology or
semantics, seems to be the driver of coarse N1 tuning for print in Chinese
children.
PMID- 27507120
TI - Effects of packaging materials on the aroma stability of Thai 'tom yam' seasoning
powder as determined by descriptive sensory analysis and gas chromatography-mass
spectrometry.
AB - BACKGROUND: Changes in the aroma characteristics of Thai 'tom yam' seasoning
powder, containing lemongrass, galangal and kaffir lime leaf, as affected by
different packaging materials were assessed using quantitative descriptive
analysis (QDA) and gas chromatography-mass spectrometry (GC-MS). The descriptive
aroma attributes for lemongrass, galangal and kaffir lime leaf powders were
developed by the QDA panel. The mixed herb and spice seasoning powder was kept in
glass jars closed with different packaging materials (Nylon 6, polyethylene
terephthalate (PET) and polylactic acid (PLA)) stored at 38 degrees C
(accelerated storage condition), and evaluated by the trained QDA panel during
storage for 49 days. RESULTS: The descriptive words for Thai 'tom yam' seasoning
powder developed by the trained panelists were lemongrass, vinegary and leafy for
lemongrass, galangal and kaffir lime leaf dried powder, respectively. The aroma
intensities significantly (P <= 0.05) decreased with increased storage time.
However, the intensity scores for aroma attributes were not significantly (P >
0.05) different among the packaging materials studied. The major components in
Thai 'tom yam' seasoning powder, quantified by GC-MS, were estragole,
bicyclo[3.1.1]heptane, beta-bisabolene, benzoic acid and 2-ethylhexyl salicylate.
The concentrations of major aroma compounds significantly (P <= 0.05) decreased
with storage time. CONCLUSION: Aroma stability of Thai 'tom yam' powder can be
determined by descriptive sensory evaluation and GC-MS analysis. Nylon, PET and
PLA exhibited similar aroma barrier properties against key aroma compounds in
Thai 'tom yam'. This information can be used for prediction of aroma loss through
packaging materials during storage of Thai 'tom yam'. (c) 2016 Society of
Chemical Industry.
PMID- 27507121
TI - Progress to extinction: increased specialisation causes the demise of animal
clades.
AB - Animal clades tend to follow a predictable path of waxing and waning during their
existence, regardless of their total species richness or geographic coverage.
Clades begin small and undifferentiated, then expand to a peak in diversity and
range, only to shift into a rarely broken decline towards extinction. While this
trajectory is now well documented and broadly recognised, the reasons underlying
it remain obscure. In particular, it is unknown why clade extinction is universal
and occurs with such surprising regularity. Current explanations for
paleontological extinctions call on the growing costs of biological interactions,
geological accidents, evolutionary traps, and mass extinctions. While these are
effective causes of extinction, they mainly apply to species, not clades.
Although mass extinctions is the undeniable cause for the demise of a sizeable
number of major taxa, we show here that clades escaping them go extinct because
of the widespread tendency of evolution to produce increasingly specialised,
sympatric, and geographically restricted species over time.
PMID- 27507122
TI - Rhizobia: tractable models for bacterial evolutionary ecology.
PMID- 27507123
TI - From discrete molecule, to polymer, to MOF: mapping the coordination chemistry of
Cd(II) using (113)Cd solid-state NMR.
AB - Studies of three related Cd(II) systems (a discrete [Cd(II)2] unit, a one
dimensional [Cd(II)2]n coordination polymer and a Cd(II)-based MOF) all derived
from the ligand 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine, reveal an exceptionally
rare example of (113)Cd-(113)Cd J coupling in the polymer that is detectable by
solid-state NMR ((2)JCd-Cd = ~65 Hz).
PMID- 27507124
TI - Predisposing factors for poor prognosis of angiosarcoma of the scalp and face:
Systematic review and meta-analysis.
AB - BACKGROUND: Angiosarcoma of the scalp and face is an aggressive tumor with a high
rate of local recurrence. Although many previous studies have demonstrated risk
factors for poor prognosis, debate remains. We identified the predisposing
factors for poor prognosis through comprehensive review of selected studies with
meta-analysis. METHODS: A systematic literature review and meta-analysis were
performed using MEDLINE, EMBASE, and Cochrane databases. Nine variables were
extracted from the included studies and evaluated based on a 5-year survival
rate. The Newcastle-Ottawa scale was used to assess the quality of the studies.
RESULTS: The search strategy identified 89 publications. After screening, 11
articles were selected for review. Age, size, site of tumor, margin status, and
surgery associated with poor angiosarcoma prognosis were identified. CONCLUSION:
Although further investigation of long-term and prospective studies is needed, we
identified 5 variables as predisposing factors for poor prognosis of angiosarcoma
through meta-analysis. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 380-386,
2017.
PMID- 27507125
TI - [Early diagnosis of anal intraepithelial neoplasia associated with human
papillomavirus. What is the best strategy?].
PMID- 27507126
TI - Stressors and expectations of undergraduate nursing students during clinical
practice in Singapore.
AB - Nursing students have experienced stress because they need to focus on academic
performance while being exposed to a clinical environment. The study aimed to
identify the contributing factors of stress and the clinical environment
expectations of undergraduate nursing students during their clinical practice at
a university in Singapore. A cross-sectional descriptive study design using
validated surveys was adopted. The Stressors in Nursing Students and the Clinical
Learning Environment Inventory questionnaires were used to collect the data in
January 2014. A total of 285 nursing students participated in this study. The
results showed that third year nursing students had higher stress levels than
first year and second year students. Satisfaction in terms of fulfilment among
nursing students during clinical practice was found to be the most influential
factor in predicting stress. The study suggests that the nursing faculty needs to
be more concerned about nursing students' stress level and provide more support
to third year students. In addition, students' satisfaction should be considered
when developing a clinical curriculum.
PMID- 27507127
TI - Comparing the effects of Essix and Hawley retainers on the acoustics of speech.
AB - Objective: The aim of this study was to compare the effects of two retainer types
(Essix and Hawley) on speech performance. Subjects and methods: The speech
articulation of 30 patients was evaluated prospectively. Five patients did not
appear during the follow-up periods. The patients were randomly divided into
retention groups by treatment allocation cards as Essix and Hawley. The Essix
group included 13 participants with a mean age of 15.3+/-2.4 years; the Hawley
group included 12 participants with a mean age of 16.3+/-2.56 years. Speech sound
assessments were performed on the first day and 1 week, 4 weeks, and 3 months
later. On the first day, the assessments were conducted prior to inserting the
retainers, immediately after maxillary and mandibular retainer application,
individually, and with both retainers applied. The acoustic analyses were
obtained using spectral and temporal parameters. Results: Statistical analyses
were performed with IBM SPSS for Windows, version 20. A P value less than 0.05
was considered statistically significant. The most apparent changes were found in
the [a] vowel in the Hawley group, the [e] vowel in the Essix group, and the [u]
vowel in both groups (P < 0.05). While the number of affected consonant-vowel
couples in the Essix group was low, alterations were common in the Hawley group.
There was a statistically significant difference (P < 0.05) in voice onset time
of the [d] sound between the groups. Limitations: The trial had a small sample
size and a short follow-up period. Conclusions: The Hawley retainer affected
articulatory movements in consonant-vowel combinations more prominently than the
Essix retainer did. Voice onset time of the consonant [d] in the Hawley group was
shorter than normal, indicating rapid articulatory movement in the alveolar
region.
PMID- 27507128
TI - A Phase II Study of XELOX and Cetuximab as First-Line Therapy in Patients With
KRAS Wild Type Metastatic Colorectal Cancer (FLEET2 Study).
AB - BACKGROUND: Despite the comparable clinical benefit of XELOX (capecitabine with
oxaliplatin) and FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), the value
of XELOX treatment in combination with cetuximab for metastatic colorectal cancer
(mCRC) remains largely unknown. PATIENTS AND METHODS: In this clinical trial we
evaluated the efficacy and safety of weekly/biweekly cetuximab administration
combined with biweekly XELOX in patients with previously untreated v-Ki-ras2
Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type mCRC. The primary end
point was response rate (RR) with confirmation, and the secondary end points
included progression-free survival (PFS), overall survival (OS), disease control
rate (DCR), dose intensity, and the safety of the protocol treatment. RESULTS:
Forty patients who fulfilled the inclusion criteria participated in this study.
The median treatment cycle number was 8 and the median dose intensities were 218
mg/m2/wk for cetuximab, 34 mg/m2/wk for oxaliplatin, and 821 mg/m2/d for
capecitabine. One patient showed complete response and partial response was
observed in 19 patients, giving an overall RR of 50% (95% confidence interval
[CI], 33.8%-66.2%). Stable disease was obtained in 13 patients, resulting in a
DCR of 82.5% (95% CI, 67.2%-92.7%). The PFS was 6.5 months (95% CI, 3.5-9.6
months), and the OS was 24.3 months (95% CI, 14.9-33.7 months). The safety
profile revealed the common Grade 3/4 adverse events to be acneiform eruption
(12.5%), peripheral neuropathy (7.5%), and elevated alanine transaminase levels
(7.5%). Grade 3/4 thrombocytopenia and neutropenia occurred only in 5.0% and 2.5%
of the patients, respectively. Grade 1 hand-foot syndrome (HFS) was not uncommon
(20%), whereas Grade 2/3 HFS occurred in only 3 patients (7.5%). No deaths were
reported within 30 days of the last dose. CONCLUSION: Cetuximab with XELOX showed
a confirmed overall RR of 50%, which was within the previously reported range of
RR. The safety profile showed an acceptable rate and severity of adverse events.
In light of the several advantages of XELOX, including convenience and the
reported cost-saving aspects, further study of this combination therapy is
warranted.
PMID- 27507129
TI - Reporting of Resting-State Functional Magnetic Resonance Imaging Preprocessing
Methodologies.
AB - There has been a rapid increase in resting-state functional magnetic resonance
imaging (rs-fMRI) literature in the past few years. We aim to highlight the
variability in the current reporting practices of rs-fMRI acquisition and
preprocessing parameters. The PubMed database was searched for the selection of
appropriate articles in the rs-fMRI literature and the most recent 100 articles
were selected based on our criteria. These articles were evaluated based on a
checklist for reporting of certain preprocessing steps. All of the studies
reported the temporal resolution for the scan and the software used for the
analysis. Less than half of the studies reported physiologic monitoring,
despiking, global signal regression, framewise displacement, and volume
censoring. A majority of the studies mentioned the scanning duration, eye status,
and smoothing kernel. Overall, we demonstrate the wide variability in reporting
of preprocessing methods in rs-fMRI studies. Although there might be potential
variability in reporting across studies due to individual requirements for a
study, we suggest the need for standardizing reporting guidelines to ensure
reproducibility.
PMID- 27507130
TI - Not merely a question of self-control: The longitudinal effects of overeating
behaviors, diet quality and physical activity on dieters' perceived diet success.
AB - This longitudinal study was conducted between 2010 (T1) and 2014 (T2) on a random
sample from the general Swiss population (N = 2781, 46% male). Results showed
that dieters (restrained eaters) who reported lack of success in T2 were
overweight in T1, had higher levels of emotional and external eating, overeating,
and ambivalence toward eating palatable food in T1, and a significantly increased
body mass index (BMI) in the period between T1 and T2. Dieters who reported
success in T2 had maintained a normal BMI between T1 and T2, had a higher diet
quality in T1 and had maintained regular physical activity for at least one year
before T2. The logistic regression revealed that high levels of dispositional
self-control provided the most important predictor of being a successful dieter.
When controlling for dispositional self-control, high levels of emotional eating,
overeating, and ambivalence in T1, together with increases in these levels
between T1 and T2, were associated with a decreased likelihood of being a
successful dieter in T2. High levels of diet quality in T1 and the maintenance of
regular physical activity were associated with an increased likelihood of being a
successful dieter in T2. Results suggest that diet success and failure is a long
term phenomenon, partly but not fully explained by dispositional self-control.
Independent of self-control persistent patterns of overeating due to emotional
eating and ambivalent feelings toward eating palatable food, also explain long
term diet failure. A high diet quality and maintenance of regular physical
activity accounted for dieters' long-term success. This is the first study that
examined the long-term psychological and behavioral characteristics of successful
and unsuccessful restrained eaters.
PMID- 27507131
TI - Subjective mood and energy levels of healthy weight and overweight/obese healthy
adults on high-and low-glycemic load experimental diets.
AB - Emerging evidence suggests a positive association of diet and obesity with
depression. Researchers have examined several diet-mood hypotheses, including
investigating the extent to which carbohydrates may impact mood. There is limited
research on how glycemic load, a characteristic of carbohydrates, impacts mood in
healthy adults. Eighty-two healthy weight and overweight/obese, but otherwise
healthy, adults enrolled in a randomized, crossover controlled feeding study
testing low-compared to high-glycemic load diets. All participants completed self
report mood and energy level questionnaires during each arm of the intervention.
Diets were isocaloric and were matched by macronutrient content as a percent of
total energy. Mood was assessed with the Profile of Mood States (POMS) subscales;
tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue
inertia, and confusion-bewilderment, total mood disturbance (TMD), and negative
affect (NA) in addition to the Center for Epidemiological Studies - Depression
(CES-D) scale at baseline and end of both 28-day feeding periods. Linear mixed
models tested the intervention effect on mood, controlling for baseline POMS and
CES-D scores, diet type, diet sequence, feeding period, sex, and percent body fat
classification. The consumption of the high-glycemic load diet resulted in a 38%
higher score for depressive symptoms on the CES-D (P = 0.002) compared to the low
glycemic load diet as well as 55% higher score for TMD (P = 0.05), and 26% higher
score for fatigue/inertia (P = 0.04). In subgroup analyses, the overweight/obese
participants had 40% higher scores on the CES-D scale compared to healthy weight
participants (P = 0.05). In conclusion, a high-glycemic load diet was associated
with higher depression symptoms, total mood disturbance, and fatigue compared to
a low-glycemic load diet especially in overweight/obese, but otherwise healthy,
adults. This trial was registered at clinicaltrials.gov: NCT00622661.
PMID- 27507132
TI - Examining the relationship between selective attentional bias for food- and body
related stimuli and purging behaviour in bulimia nervosa.
AB - Previous research exploring cognitive biases in bulimia nervosa suggests that
attentional biases occur for both food-related and body-related cues. Individuals
with bulimia were compared to non-bulimic controls on an emotional-Stroop task
which contained both food-related and body-related cues. Results indicated that
bulimics (but not controls) demonstrated a cognitive bias for both food-related
and body-related cues. However, a discrepancy between the two cue-types was
observed with body-related cognitive biases showing the most robust effects and
food-related cognitive biases being the most strongly associated with the
severity of the disorder. The results may have implications for clinical practice
as bulimics with an increased cognitive bias for food-related cues indicated
increased bulimic disorder severity.
PMID- 27507133
TI - Direct phase coexistence molecular dynamics study of the phase equilibria of the
ternary methane-carbon dioxide-water hydrate system.
AB - Molecular dynamics simulation is used to predict the phase equilibrium conditions
of a ternary hydrate system. In particular, the direct phase coexistence
methodology is implemented for the determination of the three-phase coexistence
temperature of the methane-carbon dioxide-water hydrate system at elevated
pressures. The TIP4P/ice, TraPPE-UA and OPLS-UA forcefields for water, carbon
dioxide and methane respectively are used, in line with our previous studies of
the phase equilibria of the corresponding binary hydrate systems. The solubility
in the aqueous phase of the guest molecules of the respective binary and ternary
systems is examined under hydrate-forming conditions, providing insight into the
predictive capability of the methodology as well as the combination of these
forcefields to accurately describe the phase behavior of the ternary system. The
three-phase coexistence temperature is calculated at 400, 1000 and 2000 bar for
two compositions of the methane-carbon dioxide mixture. The predicted values are
compared with available calculations with satisfactory agreement. An estimation
is also provided for the fraction of the guest molecules in the mixed hydrate
phase under the conditions examined.
PMID- 27507134
TI - The role of qualitative research in adding value to a randomised controlled
trial: lessons from a pilot study of a guided e-learning intervention for
managers to improve employee wellbeing and reduce sickness absence.
AB - BACKGROUND: Despite the growing popularity of mixed-methods studies and
considerable emphasis on the potential value of qualitative research to the trial
endeavour, there remains a dearth of published studies reporting on actual
contribution. This paper presents a critically reflective account of our
experience of the actual value of undertaking qualitative research alongside a
pilot cluster randomised controlled trial of a guided e-learning intervention for
managers in an NHS Mental Health Trust to improve employee wellbeing and reduce
sickness absence. For the qualitative study we undertook 36 in-depth interviews
with key informants, managers and employees. We observed and took in-depth field
notes of 10 meetings involving managers and employees at the Trust, and the two
qualitative researchers acted as participant observers at steering committee and
monthly research team meetings. We adopted a narrative methodological orientation
alongside a thematic approach to data analysis, eliciting a rich account of the
complexities of managing stress at work. RESULTS: We identified two key
overarching roles played by the qualitative research: 'problematising' and
'contextualising'. Specifically, the qualitative data revealed and challenged
assumptions embedded in the trial about the nature of the learning process, and
exposed the slippery and contested nature of abstracted variables, on which a
trial depends. The qualitative data challenged the trial's logic model, and
provided a rich understanding of the context within which the trial and
intervention took place. CONCLUSIONS: While acknowledging the ever-present
tension in mixed-methods research between the requirements of quantitative
research to represent the social world as abstracted variables, and the goal of
qualitative research to explore and document the complexity of social phenomena,
we adopted a pragmatic position that enabled us to engage with this tension in a
productive and partially integrative way. Our critically reflective account of
the praxis of integration illuminated opportunities and challenges for maximising
the value of qualitative research to a trial. This paper sets out tangible
illustrative lessons for other mixed-methods researchers endeavouring to get the
most from qualitative research. TRIAL REGISTRATION: This study is registered as
ISRCTN58661009 . Registration was submitted on 22 April 2013 and completed on 17
June 2013.
PMID- 27507135
TI - Adherence partners are an acceptable behaviour change strategy to support calcium
and iron-folic acid supplementation among pregnant women in Ethiopia and Kenya.
AB - Antenatal calcium and iron-folic acid (IFA) supplementation can reduce maternal
mortality and morbidity. Yet, even when pregnant women have a stable supply of
supplements, forgetting is often a barrier to adherence. We assessed the
acceptability of adherence partners to support calcium and IFA supplementation
among pregnant women in Kenya and Ethiopia. Adherence partners are a behaviour
change strategy to improve adherence, where pregnant women are counselled to
select a partner (e.g. spouse, relative) to remind them to take their
supplements. We conducted trials of improved practices, a formative research
method that follows participants over time as they try a new behaviour. We
provided pregnant women in Ethiopia (n = 50) and Kenya (n = 35) with calcium and
IFA supplements and counselling, and suggested selecting an adherence partner.
For each participant, we conducted semi-structured interviews about acceptability
and adherence during four interviews over six weeks. We analysed interview
transcripts thematically and tallied numerical data. In Kenya, 28 of 35 women
agreed to try an adherence partner; almost all selected their husbands. In
Ethiopia, 42 of 50 women agreed to try an adherence partner; half asked their
husbands, others asked children or relatives. Most women who did not select
adherence partners reported not needing help or not having anyone to ask.
Participants reported adherence partners reminded and encouraged them, brought
supplements, provided food and helped address side-effects. Almost all women with
adherence partners would recommend this strategy to others. Adherence partners
are an acceptable, low-cost strategy with the potential to support antenatal
micronutrient supplementation adherence.
PMID- 27507136
TI - Reply to the comment on "Outcomes of transconjunctival sutureless 27-gauge
vitrectomy with silicone oil infusion".
PMID- 27507137
TI - Comments on outcomes of transconjunctival sutureless 27-gauge vitrectomy with
silicone oil infusion.
PMID- 27507138
TI - Impact of food model (micro)structure on the microbial inactivation efficacy of
cold atmospheric plasma.
AB - The large potential of cold atmospheric plasma (CAP) for food decontamination has
recently been recognized. Room-temperature gas plasmas can decontaminate foods
without causing undesired changes. This innovative technology is a promising
alternative for treating fresh produce. However, more fundamental studies are
needed before its application in the food industry. The impact of the food
structure on CAP decontamination efficacy of Salmonella Typhimurium and Listeria
monocytogenes was studied. Cells were grown planktonically or as surface colonies
in/on model systems. Both microorganisms were grown in lab culture media in petri
dishes at 20 degrees C until cells reached the stationary phase. Before CAP
treatment, cells were deposited in a liquid carrier, on a solid(like) surface or
on a filter. A dielectric barrier discharge reactor generated helium-oxygen
plasma, which was used to treat samples up to 10min. Although L. monocytogenes is
more resistant to CAP treatment, similar trends in inactivation behavior as for
S. Typhimurium are observed, with log reductions in the range [1.0-2.9] for S.
Typhimurium and [0.2-2.2] for L. monocytogenes. For both microorganisms, cells
grown planktonically are easily inactivated, as compared to surface colonies.
More stressing growth conditions, due to cell immobilization, result in more
resistant cells during CAP treatment. The main difference between the
inactivation support systems is the absence or presence of a shoulder phase. For
experiments in the liquid carrier, which exhibit a long shoulder, the plasma
components need to diffuse and penetrate through the medium. This explains the
higher efficacies of CAP treatment on cells deposited on a solid(like) surface or
on a filter. This research demonstrates that the food structure influences the
cell inactivation behavior and efficacy of CAP, and indicates that food intrinsic
factors need to be accounted when designing plasma treatment.
PMID- 27507139
TI - Prognostic relevance of caspase 8 -652 6N InsDel and Asp302His polymorphisms for
breast cancer.
AB - BACKGROUND: The minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N
InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated
with reduced breast cancer susceptibility. Contrarily, the presence of the -652
6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic
factor in colorectal cancer or neuroblastoma. However, prognostic relevance of
these genetic variants for breast cancer is completely unknown and is therefore
adressed by the current study. METHODS: Genotyping was performed by
pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR.
RESULTS: We observed an allele-dose dependent association between CASP8 -652 6N
InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous
deletion carriers showing lowest relative caspase 8 expression (p = 0.0131).
Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to
be a negative prognostic factor for breast cancer in terms of an allele-dose
dependent influence on overall survival (OS, p = 0.0018, p = 0.0150,
respectively). Moreover, both polymorphisms were independent predictors of OS
after adjusting for co-variats (p = 0.007, p = 0.037, respectively). Prognostic
relevance of both polymorphisms were confirmed to be independent from each other
and combined analysis of diplotypes revealed an additive influence upon OS (p =
0.0002). CONCLUSION: This is the first report, showing negative and independent
prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast
cancer. Our data provide rationale to further validate clinical utility of these
polymorphisms for breast cancer and to extend this investigation to a broad scope
of other malignancies.
PMID- 27507140
TI - Genome-wide variation in recombination rate in Eucalyptus.
AB - BACKGROUND: Meiotic recombination is a fundamental evolutionary process. It not
only generates diversity, but influences the efficacy of natural selection and
genome evolution. There can be significant heterogeneity in recombination rates
within and between species, however this variation is not well understood outside
of a few model taxa, particularly in forest trees. Eucalypts are forest trees of
global economic importance, and dominate many Australian ecosystems. We studied
recombination rate in Eucalyptus globulus using genetic linkage maps constructed
in 10 unrelated individuals, and markers anchored to the Eucalyptus reference
genome. This experimental design provided the replication to study whether
recombination rate varied between individuals and chromosomes, and allowed us to
study the genomic attributes and population genetic parameters correlated with
this variation. RESULTS: Recombination rate varied significantly between
individuals (range = 2.71 to 3.51 centimorgans/megabase [cM/Mb]), but was not
significantly influenced by sex or cross type (F1 vs. F2). Significant
differences in recombination rate between chromosomes were also evident (range =
1.98 to 3.81 cM/Mb), beyond those which were due to variation in chromosome size.
Variation in chromosomal recombination rate was significantly correlated with
gene density (r = 0.94), GC content (r = 0.90), and the number of tandem
duplicated genes (r = -0.72) per chromosome. Notably, chromosome level
recombination rate was also negatively correlated with the average genetic
diversity across six species from an independent set of samples (r = -0.75).
CONCLUSIONS: The correlations with genomic attributes are consistent with
findings in other taxa, however, the direction of the correlation between
diversity and recombination rate is opposite to that commonly observed. We argue
this is likely to reflect the interaction of selection and specific genome
architecture of Eucalyptus. Interestingly, the differences amongst chromosomes in
recombination rates appear stable across Eucalyptus species. Together with the
strong correlations between recombination rate and features of the Eucalyptus
reference genome, we maintain these findings provide further evidence for a broad
conservation of genome architecture across the globally significant lineages of
Eucalyptus.
PMID- 27507141
TI - Environmental implications of high metal content in soils of a titanium mining
zone in Kenya.
AB - Mining activities contribute to an increase of specific metal contaminants in
soils. This may adversely affect plant life and consequently impact on animal and
human health. The objective of this study was to obtain the background metal
concentrations in soils around the titanium mining in Kwale County for monitoring
its environmental impacts. Forty samples were obtained with half from topsoils
and the other from subsoils. X-ray fluorescence spectrometry was used to
determine the metal content of the soil samples. High concentrations of Ti, Mn,
Fe, and Zr were observed where Ti concentrations ranged from 0.47 to 2.8 %; Mn
0.02 to 3.1 %; Fe 0.89 to 3.1 %; and Zr 0.05 to 0.85 %. Using ratios of elemental
concentrations in topsoil to subsoil method and enrichment factors concept, the
metals were observed to be of geogenic origin with no anthropogenic input. The
high concentrations of Mn and Fe may increase their concentration levels in the
surrounding agricultural lands through deposition, thereby causing contamination
on the land and the cultivated food crops. The latter can cause adverse human
health effects. In addition, titanium mining will produce tailings containing low
level titanium concentrations, which will require proper disposal to avoid
increasing titanium concentrations in the soils of the region since it has been
observed to be phytotoxic to plants at high concentrations. The results of this
study will serve as reference while monitoring the environmental impact by the
titanium mining activities.
PMID- 27507142
TI - Effects of dispersed oil exposure on biomarker responses and growth in juvenile
wolfish Anarhichas denticulatus.
AB - This study evaluated the sensitivity of the wolfish Anarhichas denticulatus
exposed to crude oil, comparing the effects of mechanically dispersed versus
chemically dispersed oil using sub-lethal endpoints. To test the toxicity of this
controversial technique, two experiments involving exposure of the organisms for
48 h were conducted. The first experiment assessed the effects of oil exposure on
biomarker responses. The second experiment monitored the growth of juveniles over
5 weeks after exposure. Overall, this study demonstrated that polycyclic aromatic
hydrocarbon (PAH) biliary metabolites, ethoxyresorufin-O-deethylase (EROD), and
acetylcholinesterase (AChE) are appropriate biomarkers to assess exposure of A.
denticulatus. Growth rate, both in length and weight, was significantly higher in
control compared to oil exposure treatments. The lack of differences between
chemically and mechanically dispersed oils in biomarker response and growth
suggests that dispersant application is no more toxic than the natural oil
dispersion. The results indicate the potential for population-level effects
resulting from exposure to oil.
PMID- 27507143
TI - No-tillage effects on grain yield, N use efficiency, and nutrient runoff losses
in paddy fields.
AB - The effect of no-tillage (NT) on rice yield and nitrogen (N) behavior often
varies considerably from individual studies. A meta-analysis was performed to
assess quantitatively the effect of NT on rice yield and N uptake by rice, N use
efficiency (NUE, i.e., fertilizer N recovery efficiency), and nutrient runoff
losses. We obtained data from 74 rice-field experiments reported during the last
three decades (1983-2013). Results showed the NT system brought a reduction of
3.8 % in the rice yield compared with conventional tillage (CT). Soil pH of 6.5
7.5 was favorable for the improvement of rice yield with the NT system, while a
significant negative NT effect on rice yield was observed in sandy soils (p <
0.05). N rate, ranging from 120 to 180 kg N ha-1, for at least 3 years was
necessary for NT to enable rice yield comparable with that of CT. Furthermore,
the observations indicated NT reduced N uptake and NUE of the rice by 5.4 and
16.9 %, while increased the N and P exports via runoff by 15.4 and 40.1 %
compared with CT, respectively. Seedling cast transplantation, N rate within the
range 120-180 kg N ha-1, and employing NT for longer than 3 years should be
encouraged to compromise between productivity and environmental effects of NT
implementation in rice fields.
PMID- 27507144
TI - Influences of anthropogenic activities and topography on water quality in the
highly regulated Huai River basin, China.
AB - Our study analyzed the spatio-temporal trends of four major water quality
parameters (i.e., dissolved oxygen (DO), ammonium nitrogen (NH3-N), total
phosphorus (TP) and permanganate index (CODMn)) at 17 monitoring stations in one
of the most polluted large river basins, Huai River Basin, in China during 2005
to 2014. More concerns were emphasized on the attributions, e.g., anthropogenic
actives (land cover, pollution load, water temperature, and regulated flow) and
natural factors (topography) to the changes in the water quality. The seasonal
Mann-Kendall test indicated that water quality conditions were significantly
improved during the study period. The results given by the Moran's I methods
demonstrated that NH3-N and CODMn existed a weak and moderate positive spatial
autocorrelation. Two cluster centers of significant high concentrations can be
detected for DO and TP at the Mengcheng and Huaidian station, respectively, while
four cluster centers of significant low concentrations for DO at Wangjiaba and
Huaidian station in the 2010s. Multiple linear regression analysis suggested that
water temperature, regulated flow, and load of water quality could significantly
influence the water quality variations. Additionally, urban land cover was the
primary predictor for NH3-N and CODMn at large scale. The predictive ability of
regression models for NH3-N and CODMn declined as the scale decreases or the
period ranges from the 2000s to the 2010s. Topography variables of elevation and
slope, which can be treated as the important explanatory variables, exhibited
positive and negative correlations to NH3-N and CODMn, respectively. This
research can help us identify the water quality variations from the scale-process
interactions and provide a scientific basis for comprehensive water quality
management and decision making in the Huai River Basin and also other river
basins over the world.
PMID- 27507145
TI - Voice Outcomes following a Single Office-Based Steroid Injection for Vocal Fold
Scar.
AB - OBJECTIVE: Persistent dysphonia from vocal fold scar remains a clinical
challenge, with current therapies providing inconsistent outcomes. We evaluated
voice outcomes after a single office-based steroid injection. STUDY DESIGN: Case
series with chart review. SETTING: Academic medical center. SUBJECTS AND METHODS:
This study was based on pre- and postoperative analysis of patient-reported,
perceptual, acoustic, aerodynamic, and videostroboscopic parameters. The sample
comprised 25 patients undergoing office-based dexamethasone injection into the
superficial lamina propria for mild/moderate vocal fold scar. Average follow-up
was 13.7 +/- 4.4 weeks; patients completed 3.5 +/- 2.3 sessions of voice therapy
between assessments. Complete data sets were not available for each parameter;
sample size is noted with results. RESULTS: Voice handicap index (n = 24; P <
.001) and glottal function index (n = 22; P < .001) decreased after injection.
Total GRBAS score (grade, roughness, breathiness, asthenia, strain) decreased (n
= 25; P < .001). Fundamental frequency range increased (n = 24; P = .024).
Phonation threshold pressure decreased (n = 14; P = .017). Videostroboscopic
parameters of vocal fold edge (P = .004), glottic closure (P = .003), and right
mucosal wave (P = .016) improved after injection. CONCLUSIONS: Office-based
steroid injection combined with voice therapy for mild/moderate vocal fold scar
is associated with improved patient-reported and functional voice measures. These
findings provide preliminary support for this approach. Importantly, the
procedure is low risk and can be performed in the office, thus offering a simple
treatment alternative to patients with a disorder that has traditionally been
difficult to manage. Prospective studies evaluating the effects of multiple
injections are warranted.
PMID- 27507146
TI - Genetic Associations Between Personality Traits and Lifetime Reproductive Success
in Humans.
AB - Personality has been associated with reproductive success in humans and other
animals, suggesting potential evolutionary selection pressures. However, studies
to date have only examined these associations on a phenotypic level, which may be
inadequate in estimating evolutionary change. Using a large longitudinal twin
dataset of contemporary Finns, we compared the phenotypic (breeder's equation)
and genetically informed (the Robertson-Price identity) associations between
lifetime reproductive success (LRS) and two personality traits-neuroticism and
extraversion. Neuroticism was not associated with LRS at the phenotypic nor
genetic level, while extraversion was associated with higher LRS in men both
phenotypically and genetically. Compared to the univariate phenotypic analysis,
the genetic analysis suggested a larger selection response of extraversion, and a
selection response of neuroticism due to indirect selection. We estimated that
neuroticism decreases by .05 standard deviations and extraversion increases by
.11 standard deviations by one generation. Our results highlight the importance
of considering genetic associations between personality and fitness and
investigating several inter-related personality traits and their covariance with
each other to predict responses to selection more accurately.
PMID- 27507147
TI - Measuring Metasyntactic Abilities: On a Classification of Metasyntactic Tasks.
AB - Researchers working on metasyntactic abilities (i.e., the metalinguistic ability
associated with syntax) face the problem of defining and measuring them.
Metasyntactic abilities is a multifaceted concept, which encompasses various
types of behaviours, from being able to intentionally manipulate syntactic
structures to being able to state syntactic rules, and the way in which it is
defined and measured varies greatly from one study to another. The present paper
proposes a theoretically informed classification of syntax related tasks. The
first part presents previous research defining and distinguishing various types
of syntactic and metasyntactic abilities and their interrelations. In the second
part, commonly used tasks are described and analyzed in terms of the framework
presented, with the aim of better pinpointing the type of ability measured by
each task. Ultimately, with this analysis of commonly used tasks, we hope to
offer criteria for discriminating between the various measures of metasyntactic
abilities.
PMID- 27507148
TI - Are Vocal Pitch Changes in Response to Facial Expressions of Emotions Potential
Cues of Empathy? A Preliminary Report.
AB - Previous research has demonstrated that even brief exposures to facial
expressions of emotions elicit facial mimicry in receivers in the form of
corresponding facial muscle movements. As well, vocal and verbal patterns of
speakers converge in conversations, a type of vocal mimicry. There is also
evidence of cross-modal mimicry in which emotional vocalizations elicit
corresponding facial muscle activity. Further, empathic capacity has been
associated with enhanced tendency towards facial mimicry as well as verbal
synchrony. We investigated a type of potential cross-modal mimicry in a simulated
dyadic situation. Specifically, we examined the influence of facial expressions
of happy, sad, and neutral emotions on the vocal pitch of receivers, and its
potential association with empathy. Results indicated that whereas both mean
pitch and variability of pitch varied somewhat in the predicted directions,
empathy was correlated with the difference in the variability of pitch while
speaking to the sad and neutral faces. Discussion of results considers the
dimensional nature of emotional vocalizations and possible future directions.
PMID- 27507149
TI - Ethnic difference in the prevalence of pre-diabetes and diabetes mellitus in
regions with Sami and non-Sami populations in Norway - the SAMINOR1 study.
AB - OBJECTIVE: The aim of this study was to measure the prevalence of pre-diabetes
and diabetes mellitus in rural populations of Norway, as well as to explore
potential ethnic disparities with respect to dysglycaemia in Sami and non-Sami
populations. DESIGN: Cross-sectional population-based study. METHODS: The
SAMINOR1 study was performed in 2003-2004. The study took place in regions with
both Sami and non-Sami populations and had a response rate of 60.9%. Information
in the SAMINOR1 study was collected using two self-administered questionnaires,
clinical examination and laboratory tests. The present analysis included 15,208
men and women aged 36-79 years from the SAMINOR1 study. RESULTS: Age-standardised
prevalence of pre-diabetes and diabetes mellitus among Sami men was 3.4 and 5.5%,
respectively. Corresponding values for non-Sami men were 3.3 and 4.6%. Age
standardised prevalence of pre-diabetes and diabetes mellitus for Sami women was
2.7 and 4.8%, respectively, while corresponding values for non-Sami women were
2.3 and 4.5%. Relative risk ratios for dysglycaemia among Sami participants
compared with non-Sami participants were significantly different in different
geographical regions, with the southern region having the highest prevalence of
pre-diabetes and diabetes mellitus among Sami participants. CONCLUSION: We
observed a heterogeneity in the prevalence of pre-diabetes and diabetes mellitus
in different geographical regions both within and between different ethnic
groups.
PMID- 27507150
TI - Musical preferences and learning outcome of medical students in cadaver
dissection laboratory: A Nigerian survey.
AB - Background music has been reported to enhance learning in the cadaver dissection
laboratory. This study was designed to determine the impact of various forms of
musical genre and some of their characteristics on students' learning outcome in
the dissection laboratory. Some selected musical genre in vocal and non-vocal
forms and at different tempi and volume were played as background music (BM) to
253 Medical and Dental students during various sessions of cadaver dissection.
Psychological Stress assessment was done using Psychological stress measure-9.
Participants love for music, preferred musical genre and other musical
characteristics were assessed. The impact of the various musical genre and their
characteristics on learning was done via written examination on the region
dissected during each musical session. A positive relationship was noted between
students' preference for musical genre during leisure with their preference for
BM during private study time (P<0.01). Statistically significant differences
(P<0.01) were established in the impacts of the selected musical genre on some
selected learning factors. Country and Classical music gave the highest positive
impact on the various learning factors in CDL followed by R&B. No significant
difference was noted between the cognitive values of vocal and non-vocal music.
Classical music most effectively reduced the stress induced by dissection in the
CDL while Reggae and High life musical genre created a more stressful environment
than regular background noise (P<0.01). Moderate volume level and Tempo were most
preferred during both cadaver dissection activity and leisure hours. This study
shows statistically significant differences in the cognitive values of some of
the studied musical genre and their various characteristics. The inability to
isolate the particular musical genre with these desired properties could account
for the controversies in the reports of the role of music in academic
environment.
PMID- 27507151
TI - Influence of the wording of evaluation items on outcome-based evaluation results
for large-group teaching in anatomy, biochemistry and legal medicine.
AB - Student learning outcome is an important dimension of teaching quality in
undergraduate medical education. Measuring an increase in knowledge during
teaching requires repetitive objective testing which is usually not feasible. As
an alternative, student learning outcome can be calculated from student self
ratings. Comparative self-assessment (CSA) gain reflects the performance
difference before and after teaching, adjusted for initial knowledge. It has been
shown to be a valid proxy measure of actual learning outcome derived from
objective tests. However, student self-ratings are prone to a number of
confounding factors. In the context of outcome-based evaluation, the wording of
self-rating items is crucial to the validity of evaluation results. This
randomized trial assessed whether including qualifiers in these statements
impacts on student ratings and CSA gain. First-year medical students self-rated
their initial (then-test) and final (post-test) knowledge for lectures in
anatomy, biochemistry and legal medicine, respectively, and 659 questionnaires
were retrieved. Six-point scales were used for self-ratings with 1 being the most
positive option. Qualifier use did not affect then-test ratings but was
associated with slightly less favorable post-test ratings. Consecutively, mean
CSA gain was smaller for items containing qualifiers than for items lacking
qualifiers (50.6+/-15.0% vs. 56.3+/-14.6%, p=0.079). The effect was more
pronounced (Cohen's d=0.82) for items related to anatomy. In order to increase
fairness of outcome-based evaluation and increase the comparability of CSA gain
data across subjects, medical educators should agree on a consistent approach
(qualifiers for all items or no qualifiers at all) when drafting self-rating
statements for outcome-based evaluation.
PMID- 27507152
TI - Variations in brachial plexus with respect to concomitant accompanying aberrant
arm arteries.
AB - INTRODUCTION: Variations in the brachial plexus are the rule rather than the
exception. This fact is of special interest for the anesthetist when planning
axillary block of brachial plexus. MATERIAL AND METHODS: 167 cadaver arms were
evaluated for variations in brachial plexus, with focus on the cords of the
plexus, the loop of the median nerve, and the course of the median,
musculocutaneous, ulnar, axillary and radial nerves. In addition, concomitant
arterial variations were recorded. RESULTS: In 167 arms, variations were detected
in 60 cases (36%). With 46 arms (28%) most variations concern the median nerve,
followed by 13 cases (8%) which involved the musculocutaneous nerve. Ulnar,
axillary and radial nerve variations were rare, amounting to 1.2% for each nerve.
In median nerve conditions with a shifted loop of median nerve (12%), a hidden
position of the loop or a hidden course of the beginning median nerve (8%) and a
doubled loop of median nerve (17%) were observed. In musculocutaneous nerve
conditions with a non-perforated coracobrachialis (1.8%), a doubled origin of the
nerve (1.2%) and a giving back of branches to the median nerve (1.8%) were noted.
Variations in ulnar, axillary and radial nerves concerned lower than normal
diameters. CONCLUSIONS: It must be stressed that cases which showed a hidden
position or a doubled expression of the loop of the median nerve, a hidden course
of its beginning and variable interconnections between musculocutaneous and
median nerves are of special interest for anesthetists and surgeons. Hence, it is
important to note that variations of arm arteries can be associated with brachial
plexus variations. For example, a common trunk of axillary artery followed by a
hidden loop and course of the median nerve may result in incomplete axillary
block of brachial plexus.
PMID- 27507153
TI - A silver carp skin derived collagen in bone defect treatment-A histological study
in a rat model.
AB - In recent years, there has been increasing interest in elaboration of novel
therapeutic strategies, such as the use of the marine collagen products.
Biochemical properties of marine collagen are different from those of mammalian
collagen; e.g., its extremely high solubility in diluted acid. Extracts produced
using low temperature techniques contain a number of small proteins and collagen
with preserved triple helix structure. The aim of the study was to evaluate the
influence of a new marine product Collgel(r) obtained with a unique method from a
silver carp (Hypophthalmichthys molitrix) on bone defect healing in a rat study.
For this purpose bone defects with diameters of 5mm were created in 15 animals
and subsequently filled with Collgel combined with another commercially available
material. Samples were processed for histological evaluation and a Micro-CT study
was performed. Histological analysis showed new bone formation in all groups
after 8 weeks. The bone formation was significantly increased in treated bone
lesions compared to untreated bone tissue. However no significant difference was
noted between the healing of the defects filled with xenogenic bovine derived
bone substitute alone and xenogenic, bovine derived bone substitute combined with
a marine delivered collagen. Finding from the histological examination was
confirmed in a Micro-CT study. The study has shown that the new marine product
can be used instead of conventional porcine or bovine collagen membranes in
guided bone regeneration.
PMID- 27507154
TI - Protective Effects of Arginine on Saccharomyces cerevisiae Against Ethanol
Stress.
AB - Yeast cells are challenged by various environmental stresses in the process of
industrial fermentation. As the currently main organism for bio-ethanol
production, Saccharomyces cerevisiae suffers from ethanol stress. Some amino
acids have been reported to be related to yeast tolerance to stresses. Here the
relationship between arginine and yeast response to ethanol stress was
investigated. Marked inhibitions of ethanol on cell growth, expression of genes
involved in arginine biosynthesis and intracellular accumulation of arginine were
observed. Furthermore, extracellular addition of arginine can abate the ethanol
damage largely. To further confirm the protective effects of arginine on yeast
cells, yeast strains with different levels of arginine content were constructed
by overexpression of ARG4 involved in arginine biosynthesis or CAR1 encoding
arginase. Intracellular arginine was increased by 18.9% or 13.1% respectively by
overexpression of ARG4 or disruption of CAR1, which enhanced yeast tolerance to
ethanol stress. Moreover, a 41.1% decrease of intracellular arginine was observed
in CAR1 overexpressing strain, which made yeast cells keenly sensitive to
ethanol. Further investigations indicated that arginine protected yeast cells
from ethanol damage by maintaining the integrity of cell wall and cytoplasma
membrane, stabilizing the morphology and function of organellae due to low ROS
generation.
PMID- 27507155
TI - IL-4 downregulates expression of the target receptor CD30 in neoplastic canine
mast cells.
AB - CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this
'comparative oncology' study, we examined CD30 expression and regulation in
neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2
(IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine
mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to
downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30
targeting antibody-conjugate brentuximab vedotin induces growth inhibition and
apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of
CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1
cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome
IL-4-mediated resistance, we applied drug combinations and found that brentuximab
vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in
inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4
regulated target in neoplastic canine MC.
PMID- 27507156
TI - Hypophosphatasia and the risk of atypical femur fractures: a case-control study.
AB - BACKGROUND: Case reports have linked adult hypophosphatasia as a possible cause
of atypical femur fractures (AFF) associated with bisphosphonate use. Adult
hypophosphatasia is an asymptomatic genetic condition which results in low
alkaline phosphatase and elevated pyridoxal phosphate. We conducted a case
control study to assess the role of hypophosphatasia and atypical femur fracture.
METHODS: We recruited 13 control patients who took long term bisphosphonates
without complication and 10 patients who sustained atypical femur fractures (mean
bisphosphonate use, 9 years both cohorts). Patients underwent clinical exam and
measurement of alkaline phosphatase and pyridoxal phosphate (PLP) levels. In
addition, DNA was extracted and the ALPL gene was sequenced in both cohorts.
RESULTS: Low alkaline phosphatase levels (<55 U/L) were seen in 5/10 AFF patients
and 5/13 control patients. Two control patients demonstrated low alkaline
phosphatase levels and elevated PLP. The alkaline phosphatase (ALPL) gene exons
and intron splice sites were sequenced in the atypical femur fracture and control
cohorts and no coding mutations were identified in any subjects. Atypical femur
fracture patients demonstrated more varus hip alignment (p < 0.048) with no
significant difference in mechanical axis. CONCLUSIONS: We found no evidence of
hypophosphatasia as a risk factor for atypical femur fractures. Laboratory
findings of mildly low alkaline phosphatase activity were equally common in
atypical and control cohorts and may be due to long term bisphosphonate use.
TRIAL REGISTRATION: Clinicaltrials.gov number NCT01360099 . Prospectively
registered May 20, 2011. First patient enrolled June 14, 2011.
PMID- 27507157
TI - Using systems thinking to identify workforce enablers for a whole systems
approach to urgent and emergency care delivery: a multiple case study.
AB - BACKGROUND: Overcrowding in emergency departments is a global issue, which places
pressure on the shrinking workforce and threatens the future of high quality,
safe and effective care. Healthcare reforms aimed at tackling this crisis have
focused primarily on structural changes, which alone do not deliver anticipated
improvements in quality and performance. The purpose of this study was to
identify workforce enablers for achieving whole systems urgent and emergency care
delivery. METHODS: A multiple case study design framed around systems thinking
was conducted in South East England across one Trust consisting of five
hospitals, one community healthcare trust and one ambulance trust. Data sources
included 14 clinical settings where upstream or downstream pinch points are
likely to occur including discharge planning and rapid response teams; ten
regional stakeholder events (n = 102); a qualitative survey (n = 48); and a
review of literature and analysis of policy documents including care pathways and
protocols. RESULTS: The key workforce enablers for whole systems urgent and
emergency care delivery identified were: clinical systems leadership, a single
integrated career and competence framework and skilled facilitation of work based
learning. CONCLUSIONS: In this study, participants agreed that whole systems
urgent and emergency care allows for the design and implementation of care
delivery models that meet complexity of population healthcare needs, reduce
duplication and waste and improve healthcare outcomes and patients' experiences.
For this to be achieved emphasis needs to be placed on holistic changes in
structures, processes and patterns of the urgent and emergency care system. Often
overlooked, patterns that drive the thinking and behavior in the workplace
directly impact on staff recruitment and retention and the overall effectiveness
of the organization. These also need to be attended to for transformational
change to be achieved and sustained. Research to refine and validate a single
integrated career and competence framework and to develop standards for an
integrated approach to workplace facilitation to grow the capacity of
facilitators that can use the workplace as a resource for learning is needed.
PMID- 27507158
TI - Detection of Diatoms by a Combination of Membrane Filtration and Transparentness.
AB - Diagnosis of drowning remains a difficult issue in current forensic sciences. A
large number of diatoms were lost by removing the supernatant after
centrifugation in the conventional forensic diatom test. We developed a novel
membrane filtration method to enrich diatoms from samples. A new solution using
different ratios of acetic acid and eugenol is prepared to make the membrane
transparent. These processes allow the diatom-containing membrane to be
visualized and identified easily by light microscopy. The tissues contaminated by
water rich in diatoms were detected by the new method for the recovery of
diatoms. Eleven drowning cases were analyzed by both the new method and the
conventional method to compare the sensitivity of both methods. The recovery of
the novel diatom test method was 54.2 +/- 23.1%. The positive rate of the novel
method has been proven to be superior to the conventional method in the diagnosis
of drowning.
PMID- 27507159
TI - Impact of degradable nanowires on long-term brain tissue responses.
AB - BACKGROUND: A promising approach to improve the performance of neural implants
consists of adding nanomaterials, such as nanowires, to the surface of the
implant. Nanostructured interfaces could improve the integration and
communication stability, partly through the reduction of the cell-to-electrode
distance. However, the safety issues of implanted nanowires in the brain need to
be evaluated and understood before nanowires can be used on the surface of
implants for long periods of time. To this end we here investigate whether
implanted degradable nanowires offer any advantage over non-degradable nanowires
in a long-term in vivo study (1 year) with respect to brain tissue responses.
RESULTS: The tissue response after injection of degradable silicon oxide (SiOx)
coated gallium phosphide nanowires and biostable hafnium oxide-coated GaP
nanowires into the rat striatum was compared. One year after nanowire injection,
no significant difference in microglial or astrocytic response, as measured by
staining for ED1 and glial fibrillary acidic protein, respectively, or in
neuronal density, as measured by staining for NeuN, was found between degradable
and biostable nanowires. Of the cells investigated, only microglia cells had
engulfed the nanowires. The SiOx-coated nanowire residues were primarily seen in
aggregated hypertrophic ED1-positive cells, possibly microglial cells that have
fused to create multinucleated giant cells. Occasionally, degradable nanowires
with an apparently intact shape were found inside single, small ED1-positive
cells. The biostable nanowires were found intact in microglia cells of both
phenotypes described. CONCLUSION: The present study shows that the degradable
nanowires remain at least partly in the brain over long time periods, i.e. 1
year; however, no obvious bio-safety issues for this degradable nanomaterial
could be detected.
PMID- 27507160
TI - [Mediastinal lymphomas].
AB - Lymphomas infiltrating the mediastinum are a challenge for the treating physician
as well as for the pathological diagnostics. The clinical scenario is often an
emergency situation, while the pathologist is usually confronted only with small
biopsy samples. Classical Hodgkin's lymphoma is by far the most frequently
occurring lymphoma in the mediastinum and predominantly the nodular sclerosis
subtype. In small and very sclerotic specimens it can be difficult to
morphologically detect Hodgkin and Reed-Sternberg cells and to identify the
characteristic phenotype by immunohistochemistry. Primary mediastinal large B
cell lymphomas should be distinguished from classical Hodgkin's lymphomas as the
treatment is different. This is characterized by the detection of sheets of blast
cells, which immunohistochemically show a strong B-cell phenotype (positivity for
CD20 and CD79a), while CD30 can also often be expressed. The intimate biological
relationship between classical Hodgkin's lymphomas and mediastinal large B-cell
lymphomas is illustrated by the existence of B-cell lymphomas with intermediate
features (so-called mediastinal grey zone lymphomas). It is important to
recognize and diagnose these lymphomas as they are associated with a slightly
inferior prognosis. Extranodal thymic marginal zone lymphomas of the mucosa
associated lymphoid tissue (MALT) type are a rare form of lymphoma encountered in
the mediastinum, which can be associated with autoimmune diseases. T
lymphoblastic lymphomas and leukemia, which occur predominantly in children and
young adults, represent a rapidly growing precursor cell neoplasia and must be
distinguished from thymomas in the differential diagnostics as well as from
normal and hyperplastic thymus glands.
PMID- 27507162
TI - [Not Available].
PMID- 27507161
TI - [Neuroendocrine neoplasms of the mediastinum].
AB - Primary neuroendocrine tumors (NET) in the mediastinum are very rare and among
them thymic NETs are the most common. They represent 5 % of all thymic and
mediastinal tumors. The WHO classification from 2015 subdivides thymic NETs into
three groups; low grade (typical carcinoid), intermediate grade (atypical
carcinoid) and high grade (large cell neuroendocrine carcinoma and small cell
carcinoma). Through this change of mediastinal/thymic NET classification into
three groups of malignancy, the nomenclature was adapted to that of the lungs,
while the histological criteria for each entity remained the same. Thymic NETs
typically occur in middle-aged adults and predominantly in males. Approximately
30 % are asymptomatic and the rest present with symptoms caused by local tumor
growth, distant metastases and/or endocrine manifestations. Carcinoids can also
occur as a part of multiple endocrine neoplasia type 1 (MEN1) and at the time of
diagnosis commonly present with regional lymph node or distant metastases, which
most often affect the lungs and bones. For the correct diagnosis tumor cell
morphology, mitotic count and/or necrosis are crucial. Patients with typical
carcinoids have the best prognosis, whereas the prognosis is slightly worse for
atypical carcinoids but very poor for large cell neuroendocrine carcinomas. Small
cell carcinomas have the worst prognosis and the shortest median survival time of
approximately 14 months.
PMID- 27507163
TI - Malaria control along China-Myanmar Border during 2007-2013: an integrated impact
evaluation.
AB - BACKGROUND: Implementing effective interventions remain a lot of difficulties
along all border regions. The emergence of artemisinin resistance of Plasmodium
falciparum strains in the Greater Mekong Subregion is a matter of great concern.
China has effectively controlled cross-border transmission of malaria and
artemisinin resistance of P. falciparum along the China-Myanmar border. METHODS:
A combined quantitative and qualitative study was used to collect data, and then
an integrated impact evaluation was conducted to malaria control along the China
Myanmar border during 2007-2013. RESULTS: The parasite prevalence rate (PPR) in
the five special regions of Myanmar was decreased from 13.6 % in March 2008 to
1.5 % in November 2013. Compared with the baseline (PPR in March 2008), the risk
ratio was only 0.11 [95 % confidence interval (CI), 0.09-0. 14) in November 2013,
which is equal to an 89 % reduction in the malaria burden. Annual parasite
incidence (API) across 19 Chinese border counties was reduced from 19.6 per 10
000 person-years in 2006 to 0.9 per 10 000 person-years in 2013. Compared with
the baseline (API in 2006), the API rate ratio was only 0.05(95 % CI, 0.04-0.05)
in 2013, which equates to a reduction of the malaria burden by 95.0 %. Meanwhile,
the health service system was strengthened and health inequity of marginalized
populations reduced along the international border. CONCLUSION: The effective
collaboration between China, Myanmar and the international non-governmental
organization promptly carried out the core interventions through simplified
processes. The integrated approaches dramatically decreased malaria burden of
Chinese-Myanmar border.
PMID- 27507164
TI - What's the hospitalisation's impact on background treatments of patients over 65
years.
AB - As our population aging increases, it requires a particular attention from the
health system. Indeed, elderly are often frail, with several diseases and
presenting high risk of adverse drug accident. Prescribing appropriately to the
elderly has become an important matter. Hospitalization and consultation with the
general practitioner are key moments for drug prescription. However, their real
impact on background treatments of this population has been barely evaluated. A
retrospective descriptive study was conducted with 300 patients over 65 years
old, hospitalized at the Laveran military hospital in Marseille. Treatment
modifications, consecutive to hospitalization and to the first consultation with
the general practitioner, were identified and analyzed. We found an average
prescription of 5.93 drugs in prehospital period and 66% of the patients with
polypharmacy. Drugs for cardiovascular system were the most prescribed and the
most modified. Hospitalization generated a rate of modification by prescription
of 28.5% and the consultation with the general practitioner following this
hospitalization led to further change in 48% of cases. Beside the important
prevalence of patients with polypharmacy, this study shows that hospitalization
entails a significant change in background treatments in that population at risk.
Therefore, it is important to have a consensus in the re-evaluation of these
treatments, in order to prevent the iatrogenic risk.
PMID- 27507165
TI - Wiring up pre-characterized single-photon emitters by laser lithography.
AB - Future quantum optical chips will likely be hybrid in nature and include many
single-photon emitters, waveguides, filters, as well as single-photon detectors.
Here, we introduce a scalable optical localization-selection-lithography
procedure for wiring up a large number of single-photon emitters via polymeric
photonic wire bonds in three dimensions. First, we localize and characterize
nitrogen vacancies in nanodiamonds inside a solid photoresist exhibiting low
background fluorescence. Next, without intermediate steps and using the same
optical instrument, we perform aligned three-dimensional laser lithography. As a
proof of concept, we design, fabricate, and characterize three-dimensional
functional waveguide elements on an optical chip. Each element consists of one
single-photon emitter centered in a crossed-arc waveguide configuration, allowing
for integrated optical excitation and efficient background suppression at the
same time.
PMID- 27507166
TI - Modifying a generic postoperative recovery profile instrument to an instrument
specifically targeting coronary artery bypass grafting.
AB - Patients may suffer from a wide range of postoperative symptoms after coronary
artery bypass grafting. In-depth knowledge of the recovery process is a
prerequisite for nursing interventions. However, we found no specific instrument
covering the entire range and duration of postoperative symptoms related to this
procedure. We therefore modified and extended the 19 items, generic Postoperative
Recovery Profile questionnaire for the specific evaluation of the recovery after
coronary artery bypass grafting. We here report on the development process of the
new questionnaire. Procedure-specific symptoms were identified by a literature
review and by experts. The content validity was assessed by healthcare
professionals (n = 15), inpatients (n = 12) and outpatients (n = 4). A test run
was done with inpatients (n = 10), which was followed by a test-retest
reliability evaluation with inpatients (n = 24). We identified 15 new symptoms in
the literature review and six in the content validity assessment. Only three of
the 35 items had an acceptable content validity index, but all 35 items in the
test run were reported by at least two patients. The questionnaire took 4-9
minutes to complete and was considered easy to use. The final instrument used in
the reliability test included 22 new items, and 25 of the 35 items were
satisfactory stable. To conclude, we developed a 35 items, procedure-specific
questionnaire that was easy to use and may aid systematic assessment of the
recovery after coronary artery bypass grafting.
PMID- 27507167
TI - Reaction Times to Consecutive Automation Failures: A Function of Working Memory
and Sustained Attention.
AB - OBJECTIVE: This study explored whether working memory and sustained attention
influence cognitive lock-up, which is a delay in the response to consecutive
automation failures. BACKGROUND: Previous research has demonstrated that the
information that automation provides about failures and the time pressure that is
associated with a task influence cognitive lock-up. Previous research has also
demonstrated considerable variability in cognitive lock-up between participants.
This is why individual differences might influence cognitive lock-up. The present
study tested whether working memory-including flexibility in executive
functioning-and sustained attention might be crucial in this regard. METHOD:
Eighty-five participants were asked to monitor automated aircraft functions. The
experimental manipulation consisted of whether or not an initial automation
failure was followed by a consecutive failure. Reaction times to the failures
were recorded. Participants' working-memory and sustained-attention abilities
were assessed with standardized tests. RESULTS: As expected, participants'
reactions to consecutive failures were slower than their reactions to initial
failures. In addition, working-memory and sustained-attention abilities enhanced
the speed with which participants reacted to failures, more so with regard to
consecutive than to initial failures. CONCLUSION: The findings highlight that
operators with better working memory and sustained attention have small
advantages when initial failures occur, but their advantages increase across
consecutive failures. APPLICATION: The results stress the need to consider
personnel selection strategies to mitigate cognitive lock-up in general and
training procedures to enhance the performance of low ability operators.
PMID- 27507168
TI - Influence of proximal box elevation technique on marginal integrity of adhesively
luted Cerec inlays.
AB - OBJECTIVES: This in vitro study evaluated the marginal quality of Lava Ultimate
inlays in deep proximal cavities with and without proximal box elevation (PBE)
before and after thermomechanical loading (TML). MATERIALS AND METHODS: Mesio
occluso-distal cavities with proximal boxes beneath the cementoenamel junction
(CEJ) were prepared in 24 human molars. Then, one of the proximal boxes was
elevated with Filtek Supreme above the CEJ. The specimens were divided into three
groups (n = 8). The inlays of group A were adhesively luted to the cavities with
Scotchbond Universal and Rely X Ultimate, the inlays of group B with Monobond
Plus, Syntac, and Variolink II, and the inlays of group C with Clearfil Ceramic
Primer and Panavia SA Cement. Epoxy resin replicas were taken before and after
thermomechanical loading (1,200,000 cycles, 55 degrees C/5 degrees C, max. load
50 N). Marginal integrity at the different interfaces tooth/PBE, tooth/dentine,
inlay/PBE, inlay/dentine was evaluated with scanning electron microscopy (*200).
The percentage of continuous margin (% of total proximal margin length) was
compared between the groups before and after TML. STATISTICS: Mann-Whitney U test
(p = 0.05). RESULTS: No significant differences (p > 0.05) before and after TML
were found between the three groups for bonding the inlay to dentine or to PBE
composite. CONCLUSIONS: The marginal integrities of bonding inlays directly to
dentine are not different from bonding inlays to a proximal box, which has been
elevated by a composite filling material. For deep proximal cavities, the PBE
technique could be an alternative technique to conventional methods. Clinical
research is needed to confirm.
PMID- 27507169
TI - An integrative and applicable phylogenetic footprinting framework for cis
regulatory motifs identification in prokaryotic genomes.
AB - BACKGROUND: Phylogenetic footprinting is an important computational technique for
identifying cis-regulatory motifs in orthologous regulatory regions from multiple
genomes, as motifs tend to evolve slower than their surrounding non-functional
sequences. Its application, however, has several difficulties for optimizing the
selection of orthologous data and reducing the false positives in motif
prediction. RESULTS: Here we present an integrative phylogenetic footprinting
framework for accurate motif predictions in prokaryotic genomes (MP(3)). The
framework includes a new orthologous data preparation procedure, an additional
promoter scoring and pruning method and an integration of six existing motif
finding algorithms as basic motif search engines. Specifically, we collected
orthologous genes from available prokaryotic genomes and built the orthologous
regulatory regions based on sequence similarity of promoter regions. This
procedure made full use of the large-scale genomic data and taxonomy information
and filtered out the promoters with limited contribution to produce a high
quality orthologous promoter set. The promoter scoring and pruning is implemented
through motif voting by a set of complementary predicting tools that mine as many
motif candidates as possible and simultaneously eliminate the effect of random
noise. We have applied the framework to Escherichia coli k12 genome and evaluated
the prediction performance through comparison with seven existing programs. This
evaluation was systematically carried out at the nucleotide and binding site
level, and the results showed that MP(3) consistently outperformed other popular
motif finding tools. We have integrated MP(3) into our motif identification and
analysis server DMINDA, allowing users to efficiently identify and analyze motifs
in 2,072 completely sequenced prokaryotic genomes. CONCLUSION: The performance
evaluation indicated that MP(3) is effective for predicting regulatory motifs in
prokaryotic genomes. Its application may enhance progress in elucidating
transcription regulation mechanism, thus provide benefit to the genomic research
community and prokaryotic genome researchers in particular.
PMID- 27507171
TI - Tunneling-injection in vertical quasi-2D heterojunctions enabled efficient and
adjustable optoelectronic conversion.
AB - The advent of 2D materials integration has enabled novel heterojunctions where
carrier transport proceeds thrsough different ultrathin layers. We here
demonstrate the potential of such heterojunctions on a
graphene/dielectric/semiconductor vertical stack that combines several enabling
features for optoelectronic devices. Efficient and stable light emission was
achieved through carrier tunneling from the graphene injector into prominent
states of a luminescent material. Graphene's unique properties enable fine
control of the band alignment in the heterojunction. This advantage was used to
produce vertical tunneling-injection light-emitting transistors (VtiLET) where
gating allows adjustment of the light emission intensity independent of applied
bias. This device was shown to simultaneously act as a light detecting transistor
with a linear and gate tunable sensitivity. The presented development of an
electronically controllable multifunctional light emitter, light detector and
transistor open up a new route for future optoelectronics.
PMID- 27507170
TI - Factors related to outcome of bloodstream infections due to Candida parapsilosis
complex.
AB - BACKGROUND: Although Candida albicans is the most common cause of fungal blood
stream infections (BSIs), infections due to Candida species other than C.
albicans are rising. Candida parapsilosis complex has emerged as an important
fungal pathogen and became one of the main causes of fungemia in specific
geographical areas. We analyzed the factors related to outcome of candidemia due
to C. parapsilosis in a single tertiary referral hospital over a five-year
period. METHODS: A retrospective observational study of all cases of candidemia
was carried out at a 980-bedded University Hospital in Italy. Data regarding
demographic characteristics and clinical risk factors were collected from the
patient's medical records. Antifungal susceptibility testing was performed and
MIC results were interpreted according to CLSI species-specific clinical
breakpoints. RESULTS: Of 270 patients diagnosed with Candida BSIs during the
study period, 63 (23 %) were infected with isolates of C. parapsilosis complex
which represented the second most frequently isolated yeast after C. albicans.
The overall incidence rate was 0.4 episodes/1000 hospital admissions. All the
strains were in vitro susceptible to all antifungal agents. The overall crude
mortality at 30 days was 27 % (17/63), which was significantly lower than that
reported for C. albicans BSIs (42 % [61/146], p = 0.042). Being hospitalized in
ICU resulted independently associated with a significant higher risk of mortality
(HR 4.625 [CI95% 1.015-21.080], p = 0.048). Conversely, early CVC removal was
confirmed to be significantly associated with a lower risk of mortality (HR 0.299
[CI95% 0.102-0.874], p = 0.027). Finally, the type of primary antifungal therapy
did not influence the outcome of infection. CONCLUSIONS: Candidemia due to C.
parapsilosis complex, the second most commonly causative agent of yeast BSIs in
our center, is characterized by a non-negligible mortality at 30 days. An early
CVC removal is associated with a significant reduced mortality.
PMID- 27507173
TI - A Systematic Review of the Respiratory Effects of Inhalational Marijuana.
AB - This systematic review focuses on respiratory effects of inhalational marijuana.
The systematic review of the literature was conducted using a comparative method
between 2 researchers. Abstracts were reviewed for inclusion of respiratory
effects related to inhalational marijuana. Relevant abstracts were collected, and
full text articles were retrieved for review. Articles were removed if they did
not contain burning marijuana; were animal studies; or were editorials,
systematic reviews, commentaries, non-English language, or non-respiratory
related articles. Forty-eight articles were collected and categorized by
respiratory effects. In particular, lung cancer, bullous emphysema/COPD, and
other respiratory symptoms were the primary categories. Articles were noted by
study population country, sample size, age distribution, and findings that were
pertinent to respiratory health. The research indicates that there is a risk of
lung cancer from inhalational marijuana as well as an association between
inhalational marijuana and spontaneous pneumothorax, bullous emphysema, or COPD.
A variety of symptoms have been reported by inhalational marijuana smokers,
including wheezing, shortness of breath, altered pulmonary function tests, cough,
phlegm production, bronchodilation, and other symptoms. It is important to stay
current with research findings to educate patients on this smoking behavior.
PMID- 27507172
TI - The severity of hereditary porphyria is modulated by the porphyrin exporter and
Lan antigen ABCB6.
AB - Hereditary porphyrias are caused by mutations in genes that encode haem
biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin
intermediates. A long-standing open question is why the same causal porphyria
mutations exhibit widely variable penetrance and expressivity in different
individuals. Here we show that severely affected porphyria patients harbour
variant alleles in the ABCB6 gene, also known as Lan, which encodes an ATP
binding cassette (ABC) transporter. Plasma membrane ABCB6 exports a variety of
disease-related porphyrins. Functional studies show that most of these ABCB6
variants are expressed poorly and/or have impaired function. Accordingly,
homozygous disruption of the Abcb6 gene in mice exacerbates porphyria phenotypes
in the Fech(m1Pas) mouse model, as evidenced by increased porphyrin accumulation,
and marked liver injury. Collectively, these studies support ABCB6 role as a
genetic modifier of porphyria and suggest that porphyrin-inducing drugs may
produce excessive toxicities in individuals with the rare Lan(-) blood type.
PMID- 27507174
TI - Effectiveness of Intraoral Chlorhexidine Protocols in the Prevention of
Ventilator-Associated Pneumonia: Meta-Analysis and Systematic Review.
AB - BACKGROUND: Ventilator-associated pneumonia (VAP) is common in critical patients
and related with increased morbidity and mortality. We conducted a systematic
review and meta-analysis, with intention-to-treat analysis, of randomized
controlled clinical trials that assessed the effectiveness of different intraoral
chlorhexidine protocols for the prevention of VAP. METHODS: Search strategies
were developed for the MEDLINE, EMBASE, and LILACS databases. MeSH terms were
combined with Boolean operators and used to search the databases. Eligible
studies were randomized controlled trials of mechanically ventilated subjects
receiving oral care with chlorhexidine or standard oral care protocols consisting
of or associated with the use of a placebo or no chemicals. Pooled estimates of
the relative risk and corresponding 95% CIs were calculated with random effects
models, and heterogeneity was assessed with the Cochran Q statistic and I(2).
RESULTS: The 13 included studies provided data on 1,640 subjects that were
randomly allocated to chlorhexidine (n = 834) or control (n = 806) treatments. A
preliminary analysis revealed that oral application of chlorhexidine fails to
promote a significant reduction in VAP incidence (relative risk 0.80, 95% CI 0.59
1.07, I(2) = 45%). However, subgroup analyses showed that chlorhexidine prevents
VAP development when used at 2% concentration (relative risk 0.53, 95% CI 0.31
0.91, I(2) = 0%) or 4 times/d (relative risk 0.56, 95% CI 0.38-0.81, I(2) = 0%).
CONCLUSIONS: We found that oral care with chlorhexidine is effective in reducing
VAP incidence in the adult population if administered at 2% concentration or 4
times/d.
PMID- 27507176
TI - Respiratory Care Received by Individuals With Duchenne Muscular Dystrophy From
2000 to 2011.
AB - BACKGROUND: Duchenne muscular dystrophy (DMD) causes progressive respiratory
muscle weakness and decline in function, which can go undetected without
monitoring. DMD respiratory care guidelines recommend scheduled respiratory
assessments and use of respiratory assist devices. To determine the extent of
adherence to these guidelines, we evaluated respiratory assessments and
interventions among males with DMD in the Muscular Dystrophy Surveillance,
Tracking, and Research Network (MD STARnet) from 2000 to 2011. METHODS: MD
STARnet is a population-based surveillance system that identifies all individuals
born during or after 1982 residing in Arizona, Colorado, Georgia, Hawaii, Iowa,
and western New York with Duchenne or Becker muscular dystrophy. We analyzed MD
STARnet respiratory care data for non-ambulatory adolescent males (12-17 y old)
and men (>=18 y old) with DMD, assessing whether: (1) pulmonary function was
measured twice yearly; (2) awake and asleep hypoventilation testing was performed
at least yearly; (3) home mechanical insufflation-exsufflation, noninvasive
ventilation, and tracheostomy/ventilators were prescribed; and (4) pulmonologists
provided evaluations. RESULTS: During 2000-2010, no more than 50% of both
adolescents and men had their pulmonary function monitored twice yearly in any of
the years; 67% or fewer were assessed for awake and sleep hypoventilation yearly.
Although the use of mechanical insufflation-exsufflation and noninvasive
ventilation is probably increasing, prior use of these devices did not prevent
all tracheostomies, and at least 18 of 29 tracheostomies were performed due to
acute respiratory illnesses. Fewer than 32% of adolescents and men had
pulmonologist evaluations in 2010-2011. CONCLUSIONS: Since the 2004 publication
of American Thoracic Society guidelines, there have been few changes in pulmonary
clinical practice. Frequencies of respiratory assessments and assist device use
among males with DMD were lower than recommended in clinical guidelines.
Collaboration of respiratory therapists and pulmonologists with clinicians caring
for individuals with DMD should be encouraged to ensure access to the full
spectrum of in-patient and out-patient pulmonary interventions.
PMID- 27507177
TI - New Predictor of Atherosclerosis in Subjects With COPD: Atherogenic Indices.
AB - BACKGROUND: We aimed to investigate the predictor role of the plasma levels of
lipid parameters and atherogenic indices on development of atherosclerosis in
subjects with COPD. METHODS: We retrospectively analyzed 104 male subjects
diagnosed with stable COPD in hospital records. We excluded subjects with
exacerbation, with known cardiovascular diseases and other chronic diseases,
receiving anti-hyperlipidemic treatment, without sufficient past medical history,
and lacking needed laboratory data. Additionally, 40 age-matched male healthy
controls were also enrolled. C-reactive protein, total cholesterol,
triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein
cholesterol levels of COPD and the control group were analyzed. Atherogenic
indices (atherogenic index of plasma, cardiogenic risk ratio, and atherogenic
coefficient) were calculated. RESULTS: C-reactive protein, triglyceride,
atherogenic index of plasma, cardiogenic risk ratio, and atherogenic coefficient
values were significantly higher in subjects with stable COPD than in control
subjects (P < .05 for all). High-density lipoprotein cholesterol level was
significantly lower in subjects with COPD than in the control group (P < .001). C
reactive protein, lipid profiles, and atherogenic indices were similar in lower
risk (stage A and B) and higher-risk (stage C and D) subjects with COPD.
Cardiogenic risk ratio and atherogenic coefficient were negatively correlated
with FEV1 in all stable subjects with COPD and in higher-risk subjects with COPD
(r = -0.27, P = .01 and r = -0.35, P = .01, respectively). CONCLUSIONS: We
concluded that atherogenic indices (atherogenic index of plasma, cardiogenic risk
ratio, atherogenic coefficient) could be considered as a useful predictor for
atherosclerosis and cardiovascular diseases in stable COPD patients.
Nevertheless, further prospective investigations on this issue are warranted.
PMID- 27507178
TI - Use of multivitamin, acidifier and Azolla in the diet of broiler chickens.
AB - OBJECTIVE: The experiments were carried out to measure the effect of
multivitamin, acidifier and Azolla on growth performance, profitability and lipid
profiles of blood of broiler chickens to produce safe and cost effective
broilers. METHODS: In experiment 1, 240 day-old Cobb-500 broiler chicks were fed
diets; D1 (control), D2 (D1 with 1 mL multivitamin/liter water), D3 (D1 with 1 mL
acidifier/liter water), D4 (D1 with 1 mL multivitamin and 2 mL acidifier/liter
water) having 3 replications in each, and 20 chicks/replication. In experiment 2,
150 day-old Cobb-500 broiler chicks were fed diets; T1 (control), T2 (5% Azolla
in the diet), T3 (7% Azolla in the diet) and T4 (T1 with 1 mL multivitamin and 1
mL acidifier/liter water) having 3 replications in each, and 20
chicks/replication in control, and 10 chicks/replication in the remaining dietary
treatment groups for 35 days. RESULTS: In experiment 1, the highest live weight
was observed in D4 (p<0.05), however, feed intake was statistically similar
between diets (p>0.05). The lowest feed conversion ratio (FCR) (p<0.001) and
mortality (p<0.05) were observed in D2 followed by D4, D1, and D3, respectively.
There were no significant differences between diets for feed cost and net profit
(p>0.05). However, evidently but not significantly, the highest net profit was
obtained in D2 followed by D4, D1, and D3, respectively. In experiment 2, the
highest live weight (p<0.05) and feed intake (p<0.001) were observed in T4.
Mortality (p<0.01), FCR (p<0.01), feed cost (p<0.05) and net profit (p<0.05) were
significantly different among diets. Considering net profit, T2 was the best
performing dietary group followed by T3, T1, and T4, respectively. The lowest
lipid profiles were observed in D3 followed by D1, D4, and D2, respectively
(p<0.05). In experiment 2, the lowest total cholesterol, TG, and the highest
amount of high density lipoprotein were observed in T2, followed by T3, T1, and
T4, respectively (p<0.05). Evidently but not significantly, low density
lipoprotein was the highest in T2 followed by T3, T4, and T1, respectively
(p>0.05). CONCLUSION: In conclusion, Azolla and acidifier reduced lipid profiles
of broiler chickens. Considering net profit and lipid profiles, 5% Azolla may be
the suitable dietary group for producing safe and profitable broilers. However,
more studies are needed to confirm this study prior to suggesting using Azolla in
the poultry industry.
PMID- 27507179
TI - In vitro stability evaluation of coated lipase.
AB - OBJECTIVE: The study was conducted to evaluate the stability of commercial coated
lipase (CT-LIP) in vitro. METHODS: The capsules were tested under different
conditions with a range of temperature, pH, dry heat treatment and steaming
treatment, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) in
this work, respectively. Free lipase (uncoated lipase, UC-LIP) was the control
group. Lipase relative activities measured in various treatments were used as a
reference frame to characterize the stability. RESULTS: The lipase activities
were decreased with increasing temperatures (p<0.05), and there was a markedly
decline (p<0.01) in lipase comparative activities of UC-LIP at 80 degrees C
compared with CT-LIP group. Higher relative activities of lipase were observed in
CT-LIP group compared with the free one under acidic ambient (pH 3 to 7) and an
alkaline medium (pH 8 to 12). Residual lipase activities of CT-LIP group were
increased (p<0.05) by 5.67% and 35.60% in dry heat and hydrothermal treatments,
respectively. The lipase relative activity profile of CT-LIP was raised at first
and dropped subsequently (p<0.05) compared with constantly reduced tendency of UC
LIP exposed to both SGF and SIF. CONCLUSION: The results suggest that the CT-LIP
possesses relatively higher stability in comparison with the UC-LIP in vitro. The
CT-LIP could retain the potential property to provide sustained release of lipase
and thus improved its bioavailability in the gastrointestinal tract.
PMID- 27507180
TI - The impact of diet on the composition and relative abundance of rumen microbes in
goat.
AB - OBJECTIVE: This experiment was conducted to explore the impact of diet on the
ruminal microbial community in goats. METHODS: Twelve goats were divided into two
groups and fed complete feed (CF) or all forage (AF) diet. The total microbial
DNAs in the rumen liquid were extracted. The V4 region of microbial 16S rRNA
genes was amplified and sequenced using high-throughput. Information of sequences
was mainly analyzed by QIIME 1.8.0. RESULTS: The results showed that
Bacteroidetes and Firmicutes were the most predominant microbial phyla in the
rumen of all goats. At genus level, the abundance of fiber-digesting bacteria
such as Ruminococcus and Lachnospiracea incertae sedis was significantly higher
in AF than that in CF, while the levels of fat-degrading bacterium Anaerovibrio
and protein-degrading bacterium Pseudomonas were opposite. The core shared
genera, Prevotella and Butyrivibrio were widespread in the rumen of goats and no
significant difference was observed in relative abundance between groups.
CONCLUSION: We concluded that the richness of fiber-, protein-, and fat-digesting
bacteria was affected by diet and tended to increase with the rise of their
corresponding substrate contents in the ration; some bacteria shared by all goats
maintained stable despite the difference in the ration, and they might be
essential in maintaining the normal function of rumen.
PMID- 27507181
TI - Validation of selection accuracy for the total number of piglets born in Landrace
pigs using genomic selection.
AB - OBJECTIVE: This study was to determine the relationship between estimated
breeding value and phenotype information after farrowing when juvenile selection
was made in candidate pigs without phenotype information. METHODS: After
collecting phenotypic and genomic information for the total number of piglets
born by Landrace pigs, selection accuracy between genomic breeding value
estimates using genomic information and breeding value estimates of best linear
unbiased prediction (BLUP) using conventional pedigree information were compared.
RESULTS: Genetic standard deviation (sigmaa ) for the total number of piglets
born was 0.91. Since the total number of piglets born for candidate pigs was
unknown, the accuracy of the breeding value estimated from pedigree information
was 0.080. When genomic information was used, the accuracy of the breeding value
was 0.216. Assuming that the replacement rate of sows per year is 100% and
generation interval is 1 year, genetic gain per year is 0.346 head when genomic
information is used. It is 0.128 when BLUP is used. CONCLUSION: Genetic gain
estimated from single step best linear unbiased prediction (ssBLUP) method is by
2.7 times higher than that the one estimated from BLUP method, i.e., 270% more
improvement in efficiency.
PMID- 27507182
TI - Relationships between Single Nucleotide Polymorphism Markers and Meat Quality
Traits of Duroc Breeding Stocks in Korea.
AB - This study was conducted to determine the relationships of five intragenic single
nucleotide polymorphism (SNP) markers (protein kinase adenosine monophosphate
activated gamma3 subunit [PRKAG3], fatty acid synthase [FASN], calpastatin
[CAST], high mobility group AT-hook 1 [HMGA1], and melanocortin-4 receptor
[MC4R]) and meat quality traits of Duroc breeding stocks in Korea. A total of 200
purebred Duroc gilts from 8 sires and 40 dams at 4 pig breeding farms from 2010
to 2011 reaching market weight (110 kg) were slaughtered and their carcasses were
chilled overnight. Longissimus dorsi muscles were removed from the carcass after
24 h of slaughter and used to determine pork properties including carcass weight,
backfat thickness, moisture, intramuscular fat, pH24h, shear force, redness,
texture, and fatty acid composition. The PRKAG3, FASN, CAST, and MC4R gene SNPs
were significantly associated with the meat quality traits (p<0.003). The meats
of PRKAG3 (A 0.024/G 0.976) AA genotype had higher pH, redness and texture than
those from PRKAG3 GG genotype. Meats of FASN (C 0.301/A 0.699) AA genotype had
higher backfat thickness, texture, stearic acid, oleic acid and polyunsaturated
fatty acid than FASN CC genotype. While the carcasses of CAST (A 0.373/G 0.627)
AA genotype had thicker backfat, and lower shear force, palmitoleic acid and
oleic acid content, they had higher stearic acid content than those from the CAST
GG genotype. The MC4R (G 0.208/A 0.792) AA genotype were involved in increasing
backfat thickness, carcass weight, moisture and saturated fatty acid content, and
decreasing unsaturated fatty acid content in Duroc meat. These results indicated
that the five SNP markers tested can be a help to select Duroc breed to improve
carcass and meat quality properties in crossbred pigs.
PMID- 27507183
TI - Effects of particle size of processed barley grain, enzyme addition and microwave
treatment on in vitro disappearance and gas production for feedlot cattle.
AB - OBJECTIVE: The effects of particle size of processed barley grain, enzyme
addition and microwave treatment on in vitro dry matter (DM) disappearance (DMD),
gas production and fermentation pH were investigated for feedlot cattle. METHODS:
Rumen fluid from four fistulated feedlot cattle fed a diet of 860 dry-rolled
barley grain, 90 maize silage and 50 supplement g/kg DM was used as inoculum in 3
batch culture in vitro studies. In Experiment 1, dry-rolled barley and barley
ground through a 1-, 2-, or 4-mm screen were used to obtain four substrates
differing in particle size. In Experiment 2, cellulase enzyme (ENZ) from
Acremonium cellulolyticus Y-94 was added to dry-rolled and ground barley (2-mm)
at 0, 0.1, 0.5, 1, and 2 mg/g, while Experiment 3 examined the interactions
between microwaving (0, 30, and 60 s microwaving) and ENZ addition (0, 1, and 2
mg/g) using dry-rolled barley and 2-mm ground barley. RESULTS: In Experiment 1,
decreasing particle size increased DMD and gas production, and decreased
fermentation pH (p<0.01). The DMD (g/kg DM) of the dry-rolled barley after 24 h
incubation was considerably lower (p<0.05) than that of the ground barley (119.1
dry-rolled barley versus 284.8 for 4-mm, 341.7 for 2-mm; and 358.6 for 1-mm). In
Experiment 2, addition of ENZ to dry-rolled barley increased DMD (p<0.01) and
tended to increase (p = 0.09) gas production and decreased (p<0.01) fermentation
pH, but these variables were not affected by ENZ addition to ground barley. In
Experiment 3, there were no interactions between microwaving and ENZ addition
after microwaving for any of the variables. Microwaving had minimal effects
(except decreased fermentation pH), but consistent with Experiment 2, ENZ
addition increased (p<0.01) DMD and gas production, and decreased (p<0.05)
fermentation pH of dry-rolled barley, but not ground barley. CONCLUSION: We
conclude that cellulase enzymes can be used to increase the rumen disappearance
of barley grain when it is coarsely processed as in the case of dry-rolled
barley. However, microwaving of barley grain offered no further improvements in
ruminal fermentation of barley grain.
PMID- 27507184
TI - Sex change and effective population size: implications for population genetic
studies in marine fish.
AB - Large variance in reproductive success is the primary factor that reduces
effective population size (Ne) in natural populations. In sequentially
hermaphroditic (sex-changing) fish, the sex ratio is typically skewed and biased
towards the 'first' sex, while reproductive success increases considerably after
sex change. Therefore, sex-changing fish populations are theoretically expected
to have lower Ne than gonochorists (separate sexes), assuming all other
parameters are essentially equal. In this study, we estimate Ne from genetic data
collected from two ecologically similar species living along the eastern coast of
South Africa: one gonochoristic, the 'santer' sea bream Cheimerius nufar, and one
protogynous (female-first) sex changer, the 'slinger' sea bream Chrysoblephus
puniceus. For both species, no evidence of genetic structuring, nor significant
variation in genetic diversity, was found in the study area. Estimates of
contemporary Ne were significantly lower in the protogynous species, but the same
pattern was not apparent over historical timescales. Overall, our results show
that sequential hermaphroditism may affect Ne differently over varying time
frames, and that demographic signatures inferred from genetic markers with
different inheritance modes also need to be interpreted cautiously, in relation
to sex-changing life histories.
PMID- 27507185
TI - Reducing beef consumption might not reduce emissions: response to Phalan et al.
(2016).
PMID- 27507186
TI - Early warning score: An indicator of adverse outcomes in postoperative patients
on a gynecologic oncology service.
AB - OBJECTIVE: In 2014, our hospital implemented an early warning score (EWS) to
identify inpatients at risk for clinical deterioration. EWS>=8 is associated with
>=10% mortality in medical admissions. Since postoperative hemodynamic changes
may alter EWS, we evaluated EWS in post-laparotomy patients. METHODS: Gynecologic
oncology patients admitted for laparotomy from 9/1/2014 to 7/31/2015 were
categorized by highest EWS during admission: <5, 5-7, and >=8. The primary
outcome was a composite including death, ICU transfer, rapid response team
activation, pulmonary embolus, sepsis, and reoperation. For patients with the
composite, highest EWS prior to that outcome was evaluated. Secondary outcomes
were length of stay (LOS), readmission, and transfusion. Groups were compared
using chi-square test for trend, analysis of variance, and Kruskal-Wallis tests.
A receiver operating characteristic (ROC) curve estimated the association between
EWS and the composite outcome. RESULTS: 411 patients were included: 217 (52.8%)
with EWS<5, 151 (36.7%) with EWS 5-7, and 43 (10.5%) with EWS>=8. The composite
occurred in 32.6% of patients with EWS>=8, 7.3% with EWS 5-7, and 0% with EWS<5
(p<0.01). EWS>=8 was associated with longer LOS, higher readmission rate, and
more transfusions. For the composite, the area under the ROC curve was 0.89 (95%
CI 0.84-0.94). EWS>=5 had 100% sensitivity and 56.2% specificity for the primary
outcome; EWS>=8 had 56.0% sensitivity and 92.5% specificity for the primary
outcome. CONCLUSIONS: EWS>=5 after laparotomy is associated with adverse
outcomes. Future studies should evaluate the ability of EWS to predict and
prevent these outcomes.
PMID- 27507187
TI - Teaching multiply controlled intraverbals to children and adolescents with autism
spectrum disorders.
AB - Reciprocal conversations, instructional activities, and other social interactions
are replete with multiply controlled intraverbals, examples of which have been
conceptualized in terms of conditional discriminations. Although the acquisition
of conditional discriminations has been examined extensively in the behavior
analytic literature, little research has evaluated procedures to establish
multiply controlled intraverbals. Thus, the purpose of this investigation was to
evaluate the effects of procedures based on conditional discrimination training
on the acquisition of multiply controlled intraverbals with 7 participants who
had been diagnosed with autism spectrum disorders. We evaluated the effects of
prompt delay with error correction, a differential observing response (DOR), and
a DOR plus blocked trials on the acquisition of intraverbals using a multiple
baseline design. Accuracy of intraverbal performance increased for at least 1 set
of stimuli for all participants under prompt delay with error correction
conditions; however, 4 participants required additional teaching (i.e., DOR,
modified DOR, modified prompt delay with error correction). Based on these
findings, when prompt delay with error correction is not sufficient to establish
multiply controlled intraverbals, prompted DORs may be an effective alternative.
PMID- 27507188
TI - From Clothing to Laundry Water: Investigating the Fate of Phthalates, Brominated
Flame Retardants, and Organophosphate Esters.
AB - The accumulation of phthalate esters, brominated flame retardants (BFRs) and
organophosphate esters (OPEs) by clothing from indoor air and transfer via
laundering to outdoors were investigated. Over 30 days cotton and polyester
fabrics accumulated 3475 and 1950 ng/dm(2) ?5phthalates, 65 and 78 ng/dm(2)
?10BFRs, and 1200 and 310 ng/dm(2) ?8OPEs, respectively. Planar surface area
concentrations of OPEs and low molecular weight phthalates were significantly
greater in cotton than polyester and similar for BFRs and high molecular weight
phthalates. This difference was significantly and inversely correlated with KOW,
suggesting greater sorption of polar compounds to polar cotton. Chemical release
from cotton and polyester to laundry water was >80% of aliphatic OPEs (log KOW <
4), < 50% of OPEs with an aromatic structure, 50-100% of low molecular weight
phthalates (log KOW 4-6), and < detection-35% of higher molecular weight
phthalates (log KOW > 8) and BFRs (log KOW > 6). These results support the
hypothesis that clothing acts an efficient conveyer of soluble semivolatile
organic compounds (SVOCs) from indoors to outdoors through accumulation from air
and then release during laundering. Clothes drying could as well contribute to
the release of chemicals emitted by electric dryers. The results also have
implications for dermal exposure.
PMID- 27507189
TI - Biobrane versus topical agents in the treatment of adult scald burns.
AB - BACKGROUND: Limited data is available for treatment of scald lesions in adults.
The use of the biosynthetic matrix Biobrane(r) has been suggested as treatment
option with more benefits over topical dressings. Application of Biobrane(r) in
scalds in our center led to a perceived increase of infection, secondary
deepening, surgery and length of stay. We therefore assessed the effect of
different treatment options in adult scalds in our center. METHODS: We performed
a retrospective cohort study of adult patients that have been admitted with
scalds in our center between 2011 and 2014. We assessed two groups, group 1 with
Biobrane(r) as initial treatment and group 2 with topical treatment using
polyhexanid hydrogel and fatty gauze. Primary outcome variables were rate of
secondary deepening, surgery, infection (defined as positive microbiological
swabs and antibiotic treatment) and length of stay. Total body surface area
(TBSA) as well as diabetes mellitus (DM), hypertension, smoking and alcohol
consumption as potential confounders were included. RESULTS: A total of 52
patients were included in this study. 36 patients received treatment with
Biobrane(r) and 16 with ointment and fatty gauze. No significant differences were
found for age and TBSA whereas gender ratio was different (25/11 male/female in
group 1 vs 4/12 in group 2, p=0.003). Rate of secondary deepening, surgery,
infection as well as days of hospital stay (DOHS) were comparable. Logistic and
multilinear regression showed TBSA to be a predictive factor for infection
(p=0.041), and TBSA and age for length of stay (age p=0.036; TBSA p=0.042) in
group 1. CONCLUSION: The use of Biobrane(r) in adult scald lesions is safe and
non-inferior to topical treatment options. In elder patients and larger TBSA
Biobrane(r) may increase the risk of infection or a prolonged stay in hospital.
LEVEL OF EVIDENCE: Level 3 - retrospective cohort study.
PMID- 27507190
TI - Dual inhibition of protein kinase C and p53-MDM2 or PKC and mTORC1 are novel
efficient therapeutic approaches for uveal melanoma.
AB - Uveal melanoma (UM) is the most common cancer of the eye in adults. Many UM
patients develop metastases for which no curative treatment has been identified.
Novel therapeutic approaches are therefore urgently needed. UM is characterized
by mutations in the genes GNAQ and GNA11 which activate the PKC pathway, leading
to the use of PKC inhibitors as a rational strategy to treat UM tumors.
Encouraging clinical activity has been noted in UM patients treated with PKC
inhibitors. However, it is likely that curative treatment regimens will require a
combination of targeted therapeutic agents. Employing a large panel of UM patient
derived xenograft models (PDXs), several PKC inhibitor-based combinations were
tested in vivo using the PKC inhibitor AEB071. The most promising approaches were
further investigated in vitro using our unique panel of UM cell lines. When
combined with AEB071, the two agents CGM097 (p53-MDM2 inhibitor) and RAD001
(mTORC1 inhibitor) demonstrated greater activity than single agents, with tumor
regression observed in several UM PDXs. Follow-up studies in UM cell lines on
these two drug associations confirmed their combination activity and ability to
induce cell death. While no effective treatment currently exists for metastatic
uveal melanoma, we have discovered using our unique panel of preclinical models
that combinations between PKC/mTOR inhibitors and PKC/p53-MDM2 inhibitors are two
novel and very effective therapeutic approaches for this disease. Together, our
study reveals that combining PKC and p53-MDM2 or mTORC1 inhibitors may provide
significant clinical benefit for UM patients.
PMID- 27507191
TI - Anxiety symptoms bias memory assessment in older adults.
AB - BACKGROUND: Older adults with anxiety and/or depression experience additional
memory dysfunction beyond that of the normal aging process. However, few studies
have examined test bias in memory assessments due to anxiety and/or depressive
symptoms. The current study investigated the influence of self-reported symptoms
of anxiety and depression on the measurement equivalence of memory tests in older
adults. METHOD: This is a secondary analysis of the Advanced Cognitive Training
for Independent and Vital Elderly dataset, a randomized controlled trial of
community-dwelling older adults. Baseline data were included in this study (n =
2802). Multiple indicators multiple causes modeling was employed to assess for
measurement equivalence, differential item functioning (DIF), in memory tests.
RESULTS: The DIF was present for anxiety symptoms but not for depressive
symptoms, such that higher anxiety placed older adults at a disadvantage on
measures of memory performance. Analysis of DIF impact showed that compared with
participants scoring in the bottom quartile of anxious symptoms, participants in
the upper quartile exhibited memory performance scores that were 0.26 standard
deviation lower. CONCLUSION: Anxious but not depressive symptoms introduce test
bias into the measurement of memory in older adults. This indicates that memory
models for research and clinical purposes should account for the direct
relationship between anxiety symptoms and memory tests in addition to the true
relationship between anxiety symptoms and memory construct. These findings
support routine assessments of anxiety symptoms among older adults in settings in
which cognitive testing is being conducted. Copyright (c) 2016 John Wiley & Sons,
Ltd.
PMID- 27507192
TI - Expanded Circulating Tumor Cells from a Patient with ALK-Positive Lung Cancer
Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable
Drug Sensitivity Testing: A Case Study.
AB - The emergence of liquid biopsy using circulating tumor cells (CTCs) as a resource
to identify genomic alterations in cancer presents new opportunities for
diagnosis, therapy, and surveillance. We identified EML4-ALK gene rearrangement
in expanded CTCs from a patient with ALK-positive lung adenocarcinoma. At the
time of radiographic progression, CTCs obtained from the patient revealed a drug
resistance mutation (i.e., L1196M on the ALK gene). CTCs were expanded ex vivo
and drug sensitivity testing was performed using two ALK inhibitors, crizotinib
and ceritinib. The half maximal inhibitory concentration of ceritinib was 1664 nM
compared with crizotinib (2268 nM), showing that ceritinib was a more potent ALK
inhibitor. We show that it is feasible to detect serial genetic alterations in
expanded CTCs and perform in vitro drug screening. These findings support the
clinical utility of CTCs not only for diagnosis, but also a potential tool for
drug sensitivity testing in distinct subsets of lung cancer and for personalized
precision medicine.
PMID- 27507193
TI - A method for nondestructive mechanical testing of tissues and implants.
AB - Numerous tests have been used to elucidate mechanical properties of tissues and
implants including tensile, compressive, shear, hydrostatic compression, and
three-point bending in one or more axial directions. The development of a
nondestructive test that could be applied to tissues and materials in vivo would
promote the analysis of tissue pathology as well as the design of implant
materials. The purpose of this article is to present the results of preliminary
studies demonstrating nondestructive in vitro testing of a tissue model,
decellularized human dermis, and a model implant, silicone rubber, using a
combination of optical coherence tomography (OCT), and vibrational analysis. The
results presented suggest that nondestructive vibrational testing of tissues and
materials can be used to determine the modulus of polymeric materials and the
results are similar to those found using tensile stress-strain measurements. The
advantage of this method is that the modulus can be obtained from vibrational
methods without having to approximate the tangent to the stress-strain curve,
which is difficult for nonlinear materials that have a rapidly changing slope.
(c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 15-22, 2017.
PMID- 27507194
TI - Atomic force microscopy for the investigation of molecular and cellular behavior.
AB - The present review details the methods used for the measurement of cells and
their exudates using atomic force microscopy (AFM) and outlines the general
conclusions drawn by the mechanical characterization of biological materials
through this method. AFM is a material characterization technique that can be
operated in liquid conditions, allowing its use for the investigation of the
mechanical properties of biological materials in their native environments. AFM
has been used for the mechanical investigation of proteins, nucleic acids,
biofilms, secretions, membrane bilayers, tissues and bacterial or eukaryotic
cells; however, comparison between studies is difficult due to variances between
tip sizes and morphologies, sample fixation and immobilization strategies,
conditions of measurement and the mechanical parameters used for the
quantification of biomaterial response. Although standard protocols for the AFM
investigation of biological materials are limited and minor differences in
measurement conditions may create large discrepancies, the method is nonetheless
highly effective for comparatively evaluating the mechanical integrity of
biomaterials and can be used for the real-time acquisition of elasticity data
following the introduction of a chemical or mechanical stimulus. While it is
currently of limited diagnostic value, the technique is also useful for basic
research in cancer biology and the characterization of disease progression and
wound healing processes.
PMID- 27507195
TI - Blood-borne miRNA profile-based diagnostic classifier for lung adenocarcinoma.
AB - Accumulated evidence indicates that various types of miRNA are aberrantly
expressed in lung cancer and secreted into the bloodstream. For this study, we
constructed a serum diagnostic classifier based on detailed bioinformatics
analysis of miRNA profiles from a training cohort of 143 lung adenocarcinoma
patients and 49 healthy subjects, resulting in a 20 miRNA-based classifier.
Validation performed with an independent cohort of samples from lung
adenocarcinoma patients (n = 110), healthy subjects (n = 52), and benign
pulmonary disease patients (n = 47) showed a sensitivity of 89.1% and specificity
of 94.9%, with an area under the curve value of 0.958. Notably, 90.8% of Stage I
lung adenocarcinoma cases were correctly diagnosed. Interestingly, this
classifier also detected squamous and large cell lung carcinoma cases at
relatively high rates (70.4% and 70.0%, respectively), which appears to be
consistent with organ site-dependent miRNA expression in cancer tissues. In
contrast, we observed significantly lower rates (0-35%) using samples from 96
cases of cancer in other major organs, with breast cancer the lowest. These
findings warrant a future study to realize its clinical application as a part of
diagnostic procedures for lung cancers, for which early detection and surgical
removal is presently the only hope for eventual cure.
PMID- 27507196
TI - Creation of artificial skyrmions and antiskyrmions by anisotropy engineering.
AB - Topologically non-trivial spin textures form a fundamental paradigm in solid
state physics and present unique opportunities to explore exciting phenomena such
as the topological Hall effect. One such texture is a skyrmion, in which the
spins can be mapped to point in all directions wrapping around a sphere.
Understanding the formation of these spin textures, and their energetic
stability, is crucial in order to control their behavior. In this work, we report
on controlling the perpendicular anisotropy of continuous Co/Pt multilayer films
with ion irradiation to form unique spin configurations of artificial skyrmions
and antiskyrmions that are stabilized by their demagnetization energy. We
elucidate their behavior using aberration-corrected Lorentz transmission electron
microscopy. We also discuss the energetic stability of these structures studied
through in-situ magnetizing experiments performed at room temperature, combined
with micromagnetic simulations that successfully reproduce the spin textures and
behavior. This research offers new opportunities towards creation of artificial
skyrmion or antiskyrmion lattices that can be used to investigate not only
fundamental properties of their interaction with electron currents but also
technological applications such as artificial magnonic crystals.
PMID- 27507197
TI - Wound healing effects of Bambusa vulgaris leaves.
PMID- 27507199
TI - Phytochemistry and pharmacology of Allii Macrostemonis Bulbus, a traditional
Chinese medicine.
AB - Allii Macrostemonis Bulbus (Xiebai in Chinese), as a famous traditional Chinese
medicine, has great medicinal and dietary values since ancient times. In China,
the dry bulbs of Allium macrostemon and Allium chinense are both used as its
original plants. Pharmacological studies have revealed that both of them could
increase plasminogen activator activity and prolong the effect of coagulation to
achieve antiplatelet aggregation which validates their traditional uses for the
treatment of thoracic obstruction and cardialgia in clinics. Besides, several
other significant activities, including lipid-lowering, anti-atherosclerosis,
antitumor, antispasmodic, antibacterial, antioxidant, and insecticidal
activities, have already been reported. The volatile oils, nitrogenous compounds,
and steroidal saponins are the major beneficial compounds. Among them, steroidal
saponins are considered as the characteristic constituents. In this review, the
current information concerning the phytochemistry and pharmacology of Allii
Macrostemonis Bulbus is summarized comprehensively. In addition, several research
future perspectives are presented, especially the mechanism of bioactive
components and fraction from the bulbs of Allium macrostemon and Allium chinense.
PMID- 27507200
TI - Siwu decoction attenuates oxonate-induced hyperuricemia and kidney inflammation
in mice.
AB - The aim of the study was to investigate the effects of Siwu decoction on
hyperuricemia, kidney inflammation, and dysfunction in hyperuricemic mice. Siwu
decoction at 363.8, 727.5, and 1 455 mg.kg(-1) was orally administered to
potassium oxonate-induced hyperuricemic mice for 7 days. Serum urate, creatinine,
and blood urea nitrogen levels and hepatic xanthine oxidase (XOD) activity were
measured. The protein levels of hepatic XOD and renal urate transporter 1
(URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), ATP
binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1
(OCT1), OCT2, organic cation/carnitine transporter 1 (OCTN1), OCNT2, Nod-like
receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck
like protein (ASC), Caspase-1, and interleukin-1beta (IL-1beta) were determined
by Western blotting. Renal histopathology change was obtained following
hematoxylin-eosin staining. Our results indicated that Siwu decoction
significantly reduced serum urate, creatinine and blood urea nitrogen levels and
increased fractional excretion of uric acid in hyperuricemic mice. It effectively
reduced hepatic XOD activity and protein levels in this animal model.
Furthermore, Siwu decoction down-regulated URAT1 and GLUT9 protein levels, and up
regulated the protein levels of OAT1, ABCG2, OCT1, OCT2, OCTN1, and OCTN2 in the
kidney of the hyperuricemic mice. Additionally, Siwu decoction remarkably reduced
renal protein levels of NLRP3, ASC, Caspase-1, and IL-1beta in the hyperuricemic
mice. These results suggested that Siwu decoction exhibited anti-hyperuricemic
and anti-inflammatory effects by inhibiting hepatic XOD activity, regulating
renal organic ion transporter expression, and suppressing renal NLRP3
inflammasome activation, providing the evidence for its use in the treatment of
hyperuricemia and associated kidney inflammation.
PMID- 27507201
TI - A combination of four effective components derived from Sheng-mai san attenuates
hydrogen peroxide-induced injury in PC12 cells through inhibiting Akt and MAPK
signaling pathways.
AB - The present study was designed to investigate whether a combination of four
effective components derived from Sheng-mai san (SMXZF; ginsenoside Rb1:
ginsenoside Rg1: DT-13: Schizandrol A as 6 : 9 : 4 : 5) could attenuate hydrogen
peroxide (H2O2)-induced injury in PC12 cells, focusing on the Akt and MAPK
pathways . The PC12 cells were exposed to H2O2 (400 MUmol.L(-1)) for 1 h in the
presence or absence of SMXZF pre-treatment for 24 h. Cell viability was measured
by MTT assay. The efflux of lactate dehydrogenase (LDH), the intracellular
content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD),
and caspase-3 were also determined. Cell apoptosis was measured by Hoechst 33342
staining and Annexin V-FITC/PI staining method. The expression of Bcl-2, Bax,
cleaved caspase-3, Akt, and MAPKs were detected by Western blotting analyses.
SMXZF pretreatment significantly increased the cell viability and SOD activity
and improved the cell morphological changes, while reduced the levels of LDH and
MDA at the concentrations of 0.1, 1 and 10 MUg.mL(-1). SMXZF also inhibited H2O2
induced apoptosis in PC12 cells. Moreover, SMXZF reduced the activity of caspase
3, up-regulated the protein ratio of Bcl-2 and Bax and inhibited the expression
of cleaved caspase-3, p-Akt, p-p38, p-JNK and p-ERK1/2 in H2O2-induced PC12
cells. Co-incubation of Akt inhibitor or p38 inhibitor partly attenuated the
protection of SMXZF against H2O2-injured PC12 cells. In conclusion, our findings
suggested that SMXZF attenuated H2O2-induced injury in PC12 cells by inhibiting
Akt and MAPKs signaling pathways, which might shed insights on its
neuroprotective mechanism.
PMID- 27507202
TI - Berberine enhances antidiabetic effects and attenuates untoward effects of
canagliflozin in streptozotocin-induced diabetic mice.
AB - The present study aimed at determining whether berberine can enhance the
antidiabetic effects and alleviate the adverse effects of canagliflozin in
diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the
combined effects of berberine and canagliflozin on glucose metabolism and kidney
functions were investigated. Our results showed that berberine combined with
canagliflozin (BC) increased reduction of fasting and postprandial blood glucose,
diet, and water intake compared with berberine or canagliflozin alone.
Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine
levels and lower total urine glucose excretion than canagliflozin alone. In
addition, BC showed increased phosphorylated 5' AMP-activated protein kinase
(pAMPK) expression and decreased tumor necrosis factor alpha (TNFalpha) levels in
kidneys, compared with berberine or canagliflozin alone. These results indicated
that BC was a stronger antidiabetic than berberine or canagliflozin alone with
less negative side effects on the kidneys in the diabetic mice. The antidiabetic
effect was likely to be mediated by synergically promoting the expression of
pAMPK and reducing the expression of TNFalpha in kidneys. The present study
represented the first report that canagliflozin combined with berberine was a
promising treatment for diabetes mellitus. The exact underlying mechanisms of
action should be investigated in future studies.
PMID- 27507203
TI - Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in
human gastric cancer BGC-823 cells.
AB - The aim of the study was to investigate the anti-proliferation and apoptosis
inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer
BGC-823 cells and explore the possible mechanism of action. The anti
proliferative activity was determined by MTT assay; the induction of cell cycle
arrest and apoptosis were detected by flow cytometry. Quantitative real time RT
PCR and Western blotting were used to evaluate the mRNA and protein expression
levels in mitochondrial pathway. S1 significantly reduced cell viability and
induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner.
Further studies showed that S1 increased mRNA and protein expression of Bax and
the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase
9 and procaspase-3, suggesting that the induction of apoptosis may be related to
the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These
findings suggested that S1 merits further investigation as a novel therapeutic
agent for the treatment of human gastric cancer.
PMID- 27507204
TI - Effects of diammonium glycyrrhizinate on hepatic and intestinal UDP
Glucuronosyltransferases in rats: Implication in herb-drug interactions.
AB - Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple
biochemical and pharmacological activities and is frequently used in combination
with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant
widely used in transplant patients, is metabolized by UDP-glucuronyltransferases
(UGTs). Although significant evidence supports that glycyrrhizin could interact
with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs.
The present study aimed at investigating the regulatory effects of diammonium
glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term
administration of GLN in rats induced overall metabolism of MMF, which might be
due to the induction of UGT1A protein expression. Hepatic UGT1A activity and
UGT1A mRNA and protein expression were significantly increased in GLN-treated
rats. UGT1A expression levels were also increased in the intestine, contradicting
with the observed decrease in intestinal UGT1A activities. This phenomenon may be
attributed to different concentrations of glycyrrhetinic acid (GA) in liver and
intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our
study revealed that GLN had multiple effects on the expression and activities of
UGT1A isoforms, providing a basis for a better understanding of interactions
between GLN and other drugs.
PMID- 27507205
TI - EPSAH, an exopolysaccharide from Aphanothece halophytica GR02, improves both
cellular and humoral immunity as a novel polysaccharide adjuvant.
AB - EPSAH is an exopolysaccharide from Aphanothece halophytica GR02. The present
study was designed to evaluate its toxicity and adjuvant potential in the
specific cellular and humoral immune responses in ovalbumin (OVA) in mice. EPSAH
did not cause any mortality and side effects when the mice were administered
subcutaneously twice at the dose of 50 mg.kg(-1). Hemolytic activity in vitro
indicated that EPSAH was non-hemolytic. Splenocyte proliferation in vitro was
assayed with different concentrations of EPSAH. The mice were immunized
subcutaneously with OVA 0.1 mg alone or with OVA 0.1 mg dissolved in saline
containing Alum (0.2 mg) or EPSAH (0.2, 0.4, or 0.8 mg) on Day 1 and 15. Two
weeks later, splenocyte proliferation, natural killer (NK) cell activity,
production of cytokines IL-2 from splenocytes, and serum OVA-specific antibody
titers were measured. Phagocytic activity, production of pro-inflammatory
cytokines IL-1 and IL-12 in mice peritoneal macrophages were also determined.
EPSAH showed a dose-dependent stimulating effect on mitogen-induced
proliferation. The Con A-, LPS-, and OVA-induced splenocyte proliferation and the
serum OVA-specific IgG, IgG1, and IgG2a antibody titers in the immunized mice
were significantly enhanced. EPSAH also significantly promoted the production of
Th1 cytokine IL-2. Besides, EPSAH remarkably increased the killing activities of
NK cells from splenocytes in the immunized mice. In addition, EPSAH enhanced
phagocytic activity and the generation of pro-inflammatory cytokines IL-1 and IL
12 in macrophages. These results indicated that EPSAH had a strong potential to
increase both cellular and humoral immune responses, particularly promoting the
development of Th1 polarization.
PMID- 27507206
TI - Screening and verifying potential NTCP inhibitors from herbal medicinal
ingredients using the LLC-PK1 cell model stably expressing human NTCP.
AB - NTCP is specifically expressed on the basolateral membrane of hepatocytes,
participating in the enterohepatic circulation of bile salts, especially
conjugated bile salts, to maintain bile salts homeostasis. In addition, recent
studies have found that NTCP is a functional receptor of HBV and HDV. Therefore,
it is important to study the interaction between drugs and NTCP and identify the
inhibitors/substrates of NTCP. In the present study, a LLC-PK1 cell model stably
expressing human NTCP was established, which was simple and suitable for high
throughput screening, and utilized to screen and verify the potential inhibitors
of NTCP from 102 herbal medicinal ingredients. The results showed that ginkgolic
acid (GA) (13 : 0), GA (15 : 1), GA (17 : 1), erythrosine B, silibinin, and
emodin have inhibitory effects on NTCP uptake of TCNa in a concentration
dependent manner. Among them, GA (13 : 0) and GA (15 : 1) exhibited the stronger
inhibitory effects, with IC50 values being less than 8.3 and 13.5 MUmol.L(-1),
respectively, than the classical inhibitor, cyclosporin A (CsA) (IC50 = 20.33
MUmol.L(-1)). Further research demonstrated that GA (13 : 0), GA (15 : 1), GA (17
: 1), silibinin, and emodin were not substrates of NTCP. These findings might
contribute to a better understanding of the disposition of the herbal ingredients
in vivo, especially in biliary excretion.
PMID- 27507207
TI - Cell signalling: The motif behind PP2A-B56 specificity.
PMID- 27507208
TI - Cell signalling: Signalling to cell cycle arrest.
PMID- 27507210
TI - Translation: Profiling ribosome dynamics.
PMID- 27507209
TI - Notch signalling in context.
AB - The highly conserved Notch signalling pathway functions in many different
developmental and homeostatic processes, which raises the question of how this
pathway can achieve such diverse outcomes. With a direct route from the membrane
to the nucleus, the Notch pathway has fewer opportunities for regulation than do
many other signalling pathways, yet it generates exquisitely patterned
structures, including sensory hair cells and branched arterial networks. More
confusingly, its activity promotes tissue growth and cancers in some
circumstances but cell death and tumour suppression in others. Many different
regulatory mechanisms help to shape the activity of the Notch pathway, generating
functional outputs that are appropriate for each context. These mechanisms
include the receptor-ligand landscape, the tissue topology, the nuclear
environment and the connectivity of the regulatory networks.
PMID- 27507211
TI - Nonadaptive radiation: Pervasive diet specialization by drift in scale insects?
AB - At least half of metazoan species are herbivorous insects. Why are they so
diverse? Most herbivorous insects feed on few plant species, and adaptive host
specialization is often invoked to explain their diversification. Nevertheless,
it is possible that the narrow host ranges of many herbivorous insects are
nonadaptive. Here, we test predictions of this hypothesis with comparative
phylogenetic analyses of scale insects, a group for which there appear to be few
host-use trade-offs that would select against polyphagy, and for which passive
wind-dispersal should make host specificity costly. We infer a strong positive
relationship between host range and diversification rate, and a marked asymmetry
in cladogenetic changes in diet breadth. These results are consonant with a
system of pervasive nonadaptive host specialization in which small, drift- and
extinction-prone populations are frequently isolated from persistent and
polyphagous source populations. They also contrast with the negative relationship
between diet breadth and taxonomic diversification that has been estimated in
butterflies, a disparity that likely stems from differences in the average costs
and benefits of host specificity and generalism in scale insects versus
butterflies. Our results indicate the potential for nonadaptive processes to be
important to diet-breadth evolution and taxonomic diversification across
herbivorous insects.
PMID- 27507212
TI - Embryogenesis and early skeletogenesis in the antarctic bullhead notothen,
Notothenia coriiceps.
AB - BACKGROUND: Environmental temperature influences rates of embryonic development,
but a detailed staging series for vertebrate embryos developing in the subzero
cold of Antarctic waters is not yet available from fertilization to hatching.
Given projected warming of the Southern Ocean, it is imperative to establish a
baseline to evaluate potential effects of changing climate on fish developmental
dynamics. RESULTS: We studied the Bullhead notothen (Notothenia coriiceps), a
notothenioid fish inhabiting waters between -1.9 and +2 degrees C. In vitro
fertilization produced embryos that progressed through cleavage, epiboly,
gastrulation, segmentation, organogenesis, and hatching. We compared
morphogenesis spatially and temporally to Zebrafish and medaka. Experimental
animals hatched after about 6 months to early larval stages. To help understand
skeletogenesis, we analyzed late embryos for expression of sox9 and runx2, which
regulate chondrogenesis, osteogenesis, and eye development. Results revealed
that, despite their prolonged developmental time course, N. coriiceps embryos
developed similarly to those of other teleosts with large yolk cells.
CONCLUSIONS: Our studies set the stage for future molecular analyses of
development in these extremophile fish. Results provide a foundation for
understanding the impact of ocean warming on embryonic development and larval
recruitment of notothenioid fish, which are key factors in the marine trophic
system. Developmental Dynamics 245:1066-1080, 2016. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27507213
TI - Beam and tissue factors affecting Cherenkov image intensity for quantitative
entrance and exit dosimetry on human tissue.
AB - This study's goal was to determine how Cherenkov radiation emission observed in
radiotherapy is affected by predictable factors expected in patient imaging.
Factors such as tissue optical properties, radiation beam properties, thickness
of tissues, entrance/exit geometry, curved surface effects, curvature and imaging
angles were investigated through Monte Carlo simulations. The largest physical
cause of variation of the correlation ratio between of Cherenkov emission and
dose was the entrance/exit geometry (~50%). The largest human tissue effect was
from different optical properties (~45%). Beyond these, clinical beam energy
varies the correlation ratio significantly (~20% for X-ray beams), followed by
curved surfaces (~15% for X-ray beams and ~8% for electron beams), and finally,
the effect of field size (~5% for X-ray beams). Other investigated factors which
caused variations less than 5% were tissue thicknesses and source to surface
distance. The effect of non-Lambertian emission was negligible for imaging angles
smaller than 60 degrees. The spectrum of Cherenkov emission tends to blue-shift
along the curved surface. A simple normalization approach based on the
reflectance image was experimentally validated by imaging a range of tissue
phantoms, as a first order correction for different tissue optical properties.
PMID- 27507214
TI - Blockade of FLT4 suppresses metastasis of melanoma cells by impaired lymphatic
vessels.
AB - The metastatic spread of tumor cells via lymphatic vessels affects the relapse of
tumor patients. New lymphatic vessel formation, including lymphangiogenesis, is
promoted in the tumor environment. The lymphangiogenic factor VEGF-C can mediate
lymphatic vessel formation and induce tumor metastasis by binding with FLT4. In
melanoma, metastasis via lymphatics such as lymph nodes is one of the main
predictors of poor outcome. Thus, we investigated whether blockade of FLT4 can
reduce metastasis via the suppression of lymphatic capillaries. Proliferative
lymphatic capillaries in melanoma were estimated by immunohistochemistry using
FLT4 antibody after the injection of the FLT4 antagonist MAZ51. The numbers of
tumor modules in metastasised lungs were calculated by gross examination and
lymphatic related factors were examined by qRT-PCR. MAZ51 injection resulted in
the suppression of tumor size and module number and the inhibition of
proliferative lymphatic vessels in the intratumoral region in the lung and
proliferating melanoma cells in the lung compared to those of untreated groups.
Additionally, high FLT4 and TNF-alpha were detected in melanoma-induced tissue,
while lymphatic markers such as VEGF-C, FLT4 and Prox-1 were significantly
decreased in MAZ51 treated groups, implying that anti-lymphangiogenesis by MAZ51
may provide a potential strategy to prevent tumor metastasis in melanoma and high
number of lymphatic capillaries could be used diagnosis for severe metastasis.
PMID- 27507215
TI - PDGF-D/PDGFRbeta promotes tongue squamous carcinoma cell (TSCC) progression via
activating p38/AKT/ERK/EMT signal pathway.
AB - Platelet-derived growth factor D (PDGF-D) signaling plays significant roles
during the development and progression of human malignancies via interacting with
the receptor of PDGF-D (PDGFR). Meanwhile, the majority of human tumor metastasis
is closely associated with epithelial-mesenchymal transition (EMT). However, the
underlying mechanism between PDGF-D/PDGFR signaling and EMT which involved in
tumor metastasis remain dismal. This study aimed to investigate the role of PDGF
D signaling during EMT process of tongue squamous cell carcinoma (TSCC). In our
study, the expression of PDGF-D and PDGFR were examined in primary TSCC samples
and the expression of PDGF-D was also determined in TSCC cell lines. In addition,
the correlation between PDGF-D expression and TSCC aggressive histopathological
features was analyzed. Our results implied that upregulation of PDGFRbeta in UM1
cells induced with exogenous PDGF-D can remarkably promote tumor cells
invasiveness; conversely, when using small interfering RNA (siRNA), the
invasiveness can be severely prohibited. Furthermore, PDGF-D downstream signal
molecules p38, AKT, ERK and EMT biomarkers (E-cadherin, N-cadherin, Vimentin and
snail) were measured using Western blot. Our results showed that PDGF-D can
induce p38, AKT and ERK phosphorylation; downregulate epithelial markers and
upregulate mesenchymal markers. On the contrary, PDGFRbeta siRNA significantly
prohibited p38, AKT and ERK phosphorylation; inhibited EMT process. Function
analysis revealed that PDGFRbeta siRNA obviously interfered with UM1 cell
migration and invasion, according to transwell and wound healing assay. In
conclusion, this study suggested that EMT process can be triggered by the PDGF
D/PDGFRbeta axis in TSCC, and then involved in the tumor cell invasion via
activation of p38/AKT/ERK/EMT pathway.
PMID- 27507216
TI - Roles of N287 in catalysis and product formation of amylomaltase from
Corynebacterium glutamicum.
AB - Amylomaltase catalyzes intermolecular and intramolecular transglucosylation
reactions to form linear and cyclic oligosaccharides, respectively. The aim of
this work is to investigate the structure-function relationship of amylomaltase
from a mesophilic Corynebacterium glutamicum (CgAM). Site-directed mutagenesis
was performed to substitute Tyr for Asn287 (N287Y) to determine its role in
controlling amylomaltase activity and product formation. Expression of the wild
type (WT) and N287Y was achieved by cultivating recombinant cells in the medium
containing lactose at 16 degrees C for 14 h. The purified mutated enzyme showed
a significant decrease in all transglucosylation activities while hydrolysis
activity was not changed. Optimum temperature and pH for disproportionation
reaction were slightly changed upon mutation while those for cyclization reaction
were not changed. Interestingly, N287Y showed a change in large-ring cyclodextrin
(LR-CD) product profile in which the larger size was observed together with an
increase in thermostability and substrate preference for G5 in addition to G3.
The secondary structure of the mutated enzyme was slightly changed in related to
the WT as evidenced from circular dichroism analysis. This work thus demonstrates
that N287 is required for transglucosylation activities of CgAM. Having an
aromatic residue in this position increased thermostability, changed product
profile and substrate preference but demolished most enzyme activities.
PMID- 27507217
TI - SCAMP 3 is a novel regulator of endosomal morphology and composition.
AB - Secretory Carrier Membrane Proteins (SCAMPs) are transmembrane proteins that
function in the plasma membrane, endosomes, and trans-Golgi network. Here we show
that SCAMP 3 is a novel regulator of endosomal morphology and composition. Under
certain nutrient-starved conditions, SCAMP 3 concentrates in enlarged early
endosomes. The enlarged contain ubiquitylated and non-ubiquitylated SCAMP 3 as
well as other SCAMPs, EEA1, and the ESCRT-0 protein Hrs. We demonstrate that
SCAMP 3 is sufficient to recruit Hrs to the enlarged endosomes. Taken together,
our results suggest a novel role for SCAMP 3 in modifying endosome structure
through interactions that involve its ubiquitylation and ESCRT proteins.
PMID- 27507218
TI - Potential application of microalga Spirulina platensis as a protein source.
AB - The high protein level of various microalgal species is one of the main reasons
to consider them an unconventional source of this compound. Spirulina platensis
stands out for being one of the richest protein sources of microbial origin (460
630 g kg-1 , dry matter basis), having similar protein levels when compared to
meat and soybeans. The use of S. platensis in food can bring benefits to human
health owing to its chemical composition, since it has high levels of vitamins,
minerals, phenolics, essential fatty acids, amino acids and pigments.
Furthermore, the development of new protein sources to supply the shortage of
this nutrient is an urgent need, and protein from S. platensis plays an important
role in this scenario. In this sense, extraction processes that allow maximum
protein yield and total utilization of biomass is an urgent need, and ultrasonic
waves have proven to be an effective extraction technique. The number of
scientific papers related to protein fraction from S. platensis is still limited;
thus further studies on its functional and technological properties are needed.
(c) 2016 Society of Chemical Industry.
PMID- 27507220
TI - Hexanuclear tin(ii) and mixed valence tin(ii,iv) oxide clusters within
polyoxometalates.
AB - A hexanuclear mixed valence tin oxide cluster [Sn3(2+)Sn3(4+)O15](12-) was
successfully synthesized by the solution-state selective oxidation of a tin oxide
cluster [Sn6(2+)O12](12-) within trivacant lacunary polyoxometalates, where lone
pairs on the Sn(2+) species acted as stereochemically active sites.
PMID- 27507219
TI - Normal tissue radioprotection by amifostine via Warburg-type effects.
AB - The mechanism of Amifostine (WR-2721) mediated radioprotection is poorly
understood. The effects of amifostine on human basal metabolism, mouse liver
metabolism and on normal and tumor hepatic cells were studied. Indirect
calorimetric canopy tests showed significant reductions in oxygen consumption and
of carbon dioxide emission in cancer patients receiving amifostine. Glucose
levels significantly decreased and lactate levels increased in patient venous
blood. Although amifostine in vitro did not inhibit the activity of the prolyl
hydroxylase PHD2, experiments with mouse liver showed that on a short timescale
WR-1065 induced expression of the Hypoxia Inducible Factor HIF1alpha, lactate
dehydrogenase LDH5, glucose transporter GLUT2, phosphorylated pyruvate
dehydrogenase pPDH and PDH-kinase. This effect was confirmed on normal mouse NCTC
hepatocytes, but not on hepatoma cells. A sharp reduction of acetyl-CoA and ATP
levels in NCTC cells indicated reduced mitochondrial usage of pyruvate. Transient
changes of mitochondrial membrane potential and reactive oxygen species ROS
production were evident. Amifostine selectively protects NCTC cells against
radiation, whilst HepG2 neoplastic cells are sensitized. The radiation protection
was correlates with HIF levels. These findings shed new light on the mechanism of
amifostine cytoprotection and encourage clinical research with this agent for the
treatment of primary and metastatic liver cancer.
PMID- 27507221
TI - Radiotherapy in early-stage tongue squamous cell carcinoma with minor adverse
features.
AB - BACKGROUND: Treatment for early-stage tongue squamous cell carcinoma (SCC) is
usually surgery alone. There is ambiguity regarding the impact of minor adverse
features (MAFs) on outcome and the role of postoperative radiotherapy (PORT) in
tongue SCC. METHODS: A retrospective analysis was performed on 48 patients
diagnosed with tongue SCC treated in our center. Patients with MAFs received
adjuvant PORT. Disease outcome in patients with MAFs, and the effect of PORT were
analyzed using the Kaplan-Meier method and log-rank test. RESULTS: Thirty-one
patients had T1 and 17 had T2 disease. PORT was given to 7 patients with MAFs.
Mean follow-up time was 70 months. The 2-year overall survival (OS) rate was 86%.
Perineural invasion had a significant impact on disease-free survival (DFS; p
=.05). There was an improved DFS in patients with MAFs treated with PORT (p
=.01). CONCLUSION: MAFs may have an impact on outcome in tongue SCC, and PORT can
improve disease outcome in these patients. (c) 2016 Wiley Periodicals, Inc. Head
Neck 39: 147-150, 2017.
PMID- 27507223
TI - The global prevalence of Huntington's disease: a systematic review and
discussion.
AB - The ascertained prevalence of Huntington's disease (HD) increased significantly
following the provision of diagnostic testing. A systematic review was conducted
to estimate the prevalence of HD in the post-diagnostic testing era. 22 studies
with original data pertaining to the prevalence of HD (1993-2015) were included
and analyzed. A global meta-analysis was not performed due to heterogeneity in
study methods and geographical variation. The prevalence of HD is significantly
lower in Asian populations compared with western Europe, North America and
Australia. The global variation in HD prevalence is partly explained by the
average CAG repeat lengths and frequency of different HTT gene haplotypes in the
general population. Understanding the prevalence of HD has significant
implications for healthcare resource planning.
PMID- 27507222
TI - Gut Microbiome Associates With Lifetime Cardiovascular Disease Risk Profile Among
Bogalusa Heart Study Participants.
AB - RATIONALE: Few studies have systematically assessed the influence of gut
microbiota on cardiovascular disease (CVD) risk. OBJECTIVE: To examine the
association between gut microbiota and lifetime CVD risk profile among 55
Bogalusa Heart Study participants with the highest and 57 with the lowest
lifetime burdens of CVD risk factors. METHODS AND RESULTS: 16S ribosomal RNA
sequencing was conducted on microbial DNA extracted from stool samples of the
Bogalusa Heart Study participants. alpha Diversity, including measures of
richness and evenness, and individual genera were tested for associations with
lifetime CVD risk profile. Multivariable regression techniques were used to
adjust for age, sex, and race (model 1), along with body mass index (model 2) and
both body mass index and diet (model 3). In model 1, odds ratios (95% confidence
intervals) for each SD increase in richness, measured by the number of observed
operational taxonomic units, Chao 1 index, and abundance-based coverage
estimator, were 0.62 (0.39-0.99), 0.61 (0.38-0.98), and 0.63 (0.39-0.99),
respectively. Associations were consistent in models 2 and 3. Four genera were
enriched among those with high versus low CVD risk profile in all models. Model 1
P values were 2.12*10(-3), 7.95*10(-5), 4.39*10(-4), and 1.51*10(-4) for
Prevotella 2, Prevotella 7, Tyzzerella, and Tyzzerella 4, respectively. Two
genera were depleted among those with high versus low CVD risk profile in all
models. Model 1 P values were 2.96*10(-6) and 1.82*10(-4) for Alloprevotella and
Catenibacterium, respectively. CONCLUSIONS: The current study identified
associations of overall microbial richness and 6 microbial genera with lifetime
CVD risk.
PMID- 27507224
TI - Patient participation in patient safety still missing: Patient safety experts'
views.
AB - The aim of this study was to elicit patient safety experts' views of patient
participation in promoting patient safety. Data were collected between September
and December in 2014 via an electronic semi-structured questionnaire and
interviews with Finnish patient safety experts (n = 21), then analysed using
inductive content analysis. Patient safety experts regarded patients as having a
crucial role in promoting patient safety. They generally deemed the level of
patient safety as 'acceptable' in their organizations, but reported that patient
participation in their own safety varied, and did not always meet national
standards. Management of patient safety incidents differed between organizations.
Experts also suggested that patient safety training should be increased in both
basic and continuing education programmes for healthcare professionals. Patient
participation in patient safety is still lacking in clinical practice and
systematic actions are needed to create a safety culture in which patients are
seen as equal partners in the promotion of high-quality and safe care.
PMID- 27507225
TI - UVB exposure enhanced benzanthrone-induced inflammatory responses in SKH-1 mouse
skin by activating the expression of COX-2 and iNOS through MAP kinases/NF
kappaB/AP-1 signalling pathways.
AB - This study was conducted to explore the role of UVB on benzanthrone (BA)-induced
skin inflammation and its mechanism/s. SKH-1 hairless mice were topically exposed
with BA (25 and 50 mg/kg b.wt) either alone or along with UVB (50 mJ/cm(2)) for
24 h and estimation of ROS, histopathological analysis, myeloperoxidase (MPO)
activity, mast cell staining, immunohistochemistry for COX-2 and iNOS as well as
western blotting for MAPKs, p-NF-kappaB, c-jun, c-fos COX-2 and iNOS were carried
out. Enhanced ROS generation, increased epidermal thickness, mast cell number,
MPO activity, enhanced expression of COX-2 and iNOS, MAPKs, c-jun, c-fos, NF
kappaB were found in BA either alone or when followed by UVB treatment, compared
to the control groups. Expression of COX-2, iNOS and phosphorylation of ERK1/2
were found to be more enhanced in BA and UVB- exposed group compared to BA and
UVB only group, while phosphorylation of JNK1/2, p38, NF-kappaB and expression of
c-jun and c-fos were comparable with BA and UVB only groups. In summary, we
suggest that UVB exposure enhanced BA-induced SKH-1 skin inflammation possibly
via oxidative stress-mediated activation of MAPKs-NF-kappaB/AP-1 signalling,
which subsequently increased the expression of COX-2 and iNOS and led to
inflammation in SKH-1 mouse skin.
PMID- 27507226
TI - A report on emergent uranyl binding phenomena by an amidoxime phosphonic acid co
polymer.
AB - The development of technology to harvest the uranium dissolved in seawater would
enable access to vast quantities of this critical metal for nuclear power
generation. Amidoxime polymers are the most promising platforms for achieving
this separation, yet the design of advanced adsorbents is hindered by uncertainty
regarding the uranium binding mode. In this work we use XAFS to investigate the
uranium coordination environment in an amidoxime-phosphonic acid copolymer
adsorbent. In contrast to the binding mode predicted computationally and from
small molecule studies, a cooperative chelating model is favoured, attributable
to emergent behavior resulting from inclusion of amidoxime in the polymer.
Samples exposed to seawater also display a feature consistent with a MU(2)-oxo
bridged transition metal, suggesting the formation of an in situ specific binding
site. These findings challenge long held assumptions and provide new
opportunities for the design of advanced adsorbent materials.
PMID- 27507227
TI - Implicit motor sequence learning in schizophrenia and in old age: reduced
performance only in the third session.
AB - Although there still is conflicting evidence whether schizophrenia is a
neurodegenerative disease, cognitive changes in schizophrenia resemble those
observed during normal aging. In contrast to extensively demonstrated deficits in
explicit learning, it remains unclear whether implicit sequence learning is
impaired in schizophrenia and normal aging. Implicit sequence learning was
investigated using a computerized drawing task, the 'implicit pattern learning
task (IPLT)' in 30 stable patients with schizophrenia, 30 age-matched controls
and 30 elderly subjects on two consecutive days and after 1 week (sessions 1, 2
and 3). Fixed sequence trials were intermixed with random trials, and sequence
learning was assessed by subtraction of the response time in fixed sequence
trials from random trials. Separate analyses of response times and movement
accuracy (i.e., directional errors) were performed. Explicit sequence knowledge
was assessed using three different awareness tasks. All groups learned equally
during sessions 1 and 2. In session 3, control subjects showed significantly
larger learning scores than patients with schizophrenia (p = .012) and elderly
subjects (p = .021). This group difference is mainly expressed in movement time
and directional errors. Patients with schizophrenia demonstrated less subjective
sequence awareness, and both patients with schizophrenia and elderly subjects had
less explicit sequence recall. Explicit recall was positively correlated with
task performance in all groups. After a short 24 h interval, all subjects showed
similar improvements in implicit sequence learning. However, no benefit of prior
task exposure 1 week later was observed in patients with schizophrenia and
elderly subjects compared to controls. As patients with schizophrenia and elderly
both display less explicit sequence recall, the control group superiority after 1
week could be explained by an explicit learning component. The few patients with
schizophrenia and elderly subjects who had some sequence recall could possibly
utilize this explicit knowledge to improve their task performance but did this by
distinct mechanisms.
PMID- 27507228
TI - Long-term safety, efficacy, pharmacokinetics and pharmacodynamics of omalizumab
in children with severe uncontrolled asthma.
AB - BACKGROUND: Omalizumab is effective and well-tolerated in children with moderate
to severe allergic asthma. However, the effects of long-term treatment with
omalizumab in this population haven't been well investigated. The objective of
this study is to evaluate the long-term safety, efficacy, pharmacokinetics and
pharmacodynamics of omalizumab in children with uncontrolled severe asthma.
METHODS: Thirty-eight Japanese children (aged 7-16 years) who completed the 24
week treatment core study were included in an uncontrolled extension study, in
which treatment with omalizumab continued until the pediatric indication was
approved in Japan (ClinicalTrials.gov number: NCT01328886). RESULTS: Thirty-five
patients (92.1%) completed the extension study. The median exposure throughout
the core and extension studies was 116.6 weeks (range, 46.9-151.1 weeks). The
most common adverse events were nasopharyngitis, influenza, upper respiratory
tract infection, and asthma. Serious adverse events developed in 10 patients
(26.3%), but resolved completely with additional treatments. Incidence of adverse
events didn't increase with extended exposure with omalizumab. Twenty-nine
patients (76.3%) achieved completely- or well-controlled asthma compared with 9
patients (23.7%) at the start of the extension study. QOL scores, the rates (per
year) of hospitalizations and ER visits were significantly improved compared with
the baseline of the core study [39.0 vs 48.0 (median), p < 0.001 for QOL, 1.33 vs
0.16, p < 0.001 for hospitalization, 0.68 vs 0.15, p = 0.002 for ER visits].
Remarkably, the mean total IgE level showed a decreasing trend while exposure to
omalizumab remained at steady-state. CONCLUSIONS: Long-term treatment with
omalizumab is well-tolerated and effective in children with uncontrolled severe
allergic asthma. No new safety findings were identified.
PMID- 27507229
TI - Re-evaluation of progenitor thresholds and expectations for haematopoietic
recovery based on an analysis of 810 autologous transplants: Implications for
quality assurance.
AB - Haematological engraftment was assessed in 804 autologous transplants. Neutrophil
recovery occurred in over 99% within 14 d but platelet recovery was delayed
beyond this time in 14.8%. Time to recovery was dependent on the progenitor cell
dose infused. The minimum CD34+ cell threshold adopted in this study (2 * 106
/kg) was safe although recovery was faster with a dose >5 * 106 /kg. CD34+ cell
doses of between 1 and 2 * 106 /kg were also acceptable if either the granulocyte
macrophage colony-forming cell dose exceeded 2 * 105 /kg or this dose was due to
splitting a higher yield harvest. Prompt neutrophil recovery affords important
quality assurance for laboratory processing.
PMID- 27507230
TI - The association between food insecurity and depressive symptoms severity among
pregnant women differs by social support category: a cross-sectional study.
AB - Common mental disorders, such as depression and anxiety, affect approximately 16%
of pregnant women in low- and middle-income countries. Food insecurity (FI) has
been shown to be associated with depressive symptoms. It has also been suggested
that the association between FI and depressive symptoms is moderated by social
support (SS); however, there is limited evidence of these associations among
pregnant women living in low-income and middle-income countries. We studied the
association between FI and depressive symptoms severity and assessed whether such
an association varied among Ugandan pregnant women with low vs. high SS. Cross
sectional data were collected among 403 pregnant women in northern Uganda. SS was
assessed using an eight-item version of the Duke-UNC functional SS scale. FI and
depressive symptoms were assessed by, respectively, the individually focused FI
scale and the Center for Epidemiologic Studies-Depression scale. Women were
categorized into two SS groups, based on scoring < or >= to the median SS value.
Multivariate linear regression models indicated an independent association
between FI and depressive symptoms severity. The association between FI and
depressive symptoms severity was moderated by SS i.e. was stronger among women in
the low SS category (adjusted beta (95%CI): 0.91 (0.55; 1.27)) than for women
belonging to the high SS group (0.53 (0.28; 0.78)) (adjusted p value for
interaction = 0.026). There is need for longitudinal or interventional studies
among pregnant women living in northern Uganda or similar contexts to examine the
temporal sequence of the associations among food insecurity, depressive symptoms
severity and social support. (c) 2016 John Wiley & Sons Ltd.
PMID- 27507231
TI - Refining Ovarian Cancer Test accuracy Scores (ROCkeTS): protocol for a
prospective longitudinal test accuracy study to validate new risk scores in women
with symptoms of suspected ovarian cancer.
AB - INTRODUCTION: Ovarian cancer (OC) is associated with non-specific symptoms such
as bloating, making accurate diagnosis challenging: only 1 in 3 women with OC
presents through primary care referral. National Institute for Health and Care
Excellence guidelines recommends sequential testing with CA125 and routine
ultrasound in primary care. However, these diagnostic tests have limited
sensitivity or specificity. Improving accurate triage in women with vague
symptoms is likely to improve mortality by streamlining referral and care
pathways. The Refining Ovarian Cancer Test Accuracy Scores (ROCkeTS; HTA
13/13/01) project will derive and validate new tests/risk prediction models that
estimate the probability of having OC in women with symptoms. This protocol
refers to the prospective study only (phase III). METHODS AND ANALYSIS: ROCkeTS
comprises four parallel phases. The full ROCkeTS protocol can be found at
http://www.birmingham.ac.uk/ROCKETS. Phase III is a prospective test accuracy
study. The study will recruit 2450 patients from 15 UK sites. Recruited patients
complete symptom and anxiety questionnaires, donate a serum sample and undergo
ultrasound scored as per International Ovarian Tumour Analysis (IOTA) criteria.
Recruitment is at rapid access clinics, emergency departments and elective
clinics. Models to be evaluated include those based on ultrasound derived by the
IOTA group and novel models derived from analysis of existing data sets.
Estimates of sensitivity, specificity, c-statistic (area under receiver operating
curve), positive predictive value and negative predictive value of diagnostic
tests are evaluated and a calibration plot for models will be presented. ROCkeTS
has received ethical approval from the NHS West Midlands REC (14/WM/1241) and is
registered on the controlled trials website (ISRCTN17160843) and the National
Institute of Health Research Cancer and Reproductive Health portfolios.
PMID- 27507232
TI - Evaluation of dietary cholesterol intake in elderly Chinese: a longitudinal study
from the China Health and Nutrition Survey.
AB - OBJECTIVE: This study aimed to evaluate daily cholesterol intake across
demographic factors and its food sources in elderly Chinese. DESIGN: A
longitudinal study was conducted using demographic and dietary data for elders
aged 60 and above from eight waves (1991-2011) of the China Health and Nutrition
Survey. SETTING: The data were derived from urban and rural communities of nine
provinces (autonomous regions) in China. PARTICIPANTS: There were 16 274
participants (7657 male and 8617 female) in this study. OUTCOMES: The primary
outcome was daily cholesterol intake, which was calculated by using the Chinese
Food Composition Table, based on dietary data. RESULTS: Daily consumption of
cholesterol in the elderly significantly increased by 34% from 1991 to 2011
(p<0.0001) and reached 253.9 mg on average in 2011. Secular trends in the
proportion of subjects with an intake of >300 mg/day increased significantly
during 1991-2011 (p<0.0001). The major food sources of cholesterol by ranked
order were eggs, pork, and fish and shellfish in 1991 and 2011, while organ meats
which ranked fourth in the contribution to total intake in 1991 was replaced by
poultry in 2011. Moreover, younger elders, male elders and elders from a high
income family or a highly urbanised community had higher cholesterol intakes and
larger proportions of subjects with excessive cholesterol consumption in each
survey year. CONCLUSIONS: The large growth in daily cholesterol intake may pose
major challenges for the health of elders in China. Reduced exposure to food
enriched in cholesterol is required for elderly Chinese.
PMID- 27507233
TI - Do university hospitals perform better than general hospitals? A comparative
analysis among Italian regions.
AB - OBJECTIVE: The aim of this research was to investigate how university hospitals
(UHs) perform compared with general hospitals (GHs) in the Italian healthcare
system. DESIGN AND SETTING: 27 indicators of overall performance were selected
and analysed for UHs and GHs in 10 Italian regions. The data refer to 2012 and
2013 and were selected from two performance evaluation systems based on hospital
discharge administrative data: the Inter-Regional Performance Evaluation System
developed by the Management and Health Laboratory of the Scuola Superiore
Sant'Anna of Pisa and the Italian National Outcome Evaluation Programme developed
by the National Agency for Healthcare Services. The study was conducted in 2
stages and by combining 2 statistical techniques. In stage 1, a non-parametric
Mann-Whitney U test was carried out to compare the performance of UHs and GHs on
the selected set of indicators. In stage 2, a robust equal variance test between
the 2 groups of hospitals was carried out to investigate differences in the
amount of variability between them. RESULTS: The overall analysis gave
heterogeneous results. In general, performance was not affected by being in the
UH rather than the GH group. It is thus not possible to directly associate
Italian UHs with better results in terms of appropriateness, efficiency, patient
satisfaction and outcomes. CONCLUSIONS: Policymakers and managers should further
encourage hospital performance evaluations in order to stimulate wider
competition aimed at assigning teaching status to those hospitals that are able
to meet performance requirements. In addition, UH facilities could be integrated
with other providers that are responsible for community, primary and outpatient
services, thereby creating a joint accountability for more patient-centred and
integrated care.
PMID- 27507234
TI - Impact of omalizumab on treatment of severe allergic asthma in UK clinical
practice: a UK multicentre observational study (the APEX II study).
AB - OBJECTIVE: To describe the impact of omalizumab on asthma management in patients
treated as part of normal clinical practice in the UK National Health Service
(NHS). DESIGN: A non-interventional, mixed methodology study, combining
retrospective and prospective data collection for 12 months pre-omalizumab and
post-omalizumab initiation, respectively. SETTING: Data were collected in 22 UK
NHS centres, including specialist centres and district general hospitals in the
UK. PARTICIPANTS: 258 adult patients (aged >=16 years; 65% women) with severe
persistent allergic asthma treated with omalizumab were recruited, of whom 218
(84.5%) completed the study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary
outcome measure was change in mean daily dose of oral corticosteroids (OCS)
between the 12-month pre-omalizumab and post-omalizumab initiation periods. A
priori secondary outcome measures included response to treatment, changes in OCS
dosing, asthma exacerbations, lung function, employment/education, patient
reported outcomes and hospital resource utilisation. RESULTS: The response rate
to omalizumab at 16 weeks was 82.4%. Comparing pre-omalizumab and post-omalizumab
periods, the mean (95% CIs) daily dose of OCS decreased by 1.61 (-2.41 to -0.80)
mg/patient/day (p<0.001) and hospital exacerbations decreased by 0.97 (-1.19 to
0.75) exacerbations/patient (p<0.001). Compared with baseline, lung function,
assessed by percentage of forced expiratory volume in 1 s, improved by 4.5 (2.7
to 6.3)% at 16 weeks (p<0.001; maintained at 12 months) and patient quality of
life (Asthma Quality of Life Questionnaire) improved by 1.38 (1.18 to 1.58)
points at 16 weeks (p<0.001, maintained at 12 months). 21/162 patients with
complete employment data gained employment and 6 patients lost employment in the
12-month post-omalizumab period. The mean number of A&E visits, inpatient
hospitalisations, outpatient visits (excluding for omalizumab) and number of bed
days/patient decreased significantly (p<0.001) in the 12-month post-omalizumab
period. CONCLUSIONS: These data support the beneficial effects of omalizumab on
asthma-related outcomes, quality of life and resource utilisation in unselected
patients treated in 'real-world' clinical practice.
PMID- 27507235
TI - Principal components analysis to identify influences on research communication
and engagement during an environmental disaster.
AB - OBJECTIVES: To discern community attitudes towards research engagement in Libby,
Montana, the only Superfund site for which a public health emergency has been
declared. STUDY DESIGN: Survey study of convenience samples of residents near the
Libby, Montana Superfund site. PARTICIPANTS: Residents of the Libby, Montana area
were recruited from a local retail establishment (N=120, survey 1) or a community
event (N=127, survey 2). MEASURES: Two surveys were developed in consultation
with a Community Advisory Panel. RESULTS: Principal components of survey 1 showed
four dimensions of community members' attitudes towards research engagement: (1)
researcher communication and contributions to the community, (2) identity and
affiliation of the researchers requesting participation, (3) potential personal
barriers, including data confidentiality, painful or invasive procedures and
effects on health insurance and (4) research benefits for the community, oneself
or family. The score on the first factor was positively related to desire to
participate in research (r=0.31, p=0.01). Scores on factors 2 and 3 were higher
for those with diagnosis of asbestos-related disease (ARD) in the family (Cohen's
d=0.41, 0.57). Survey 2 also found more positive attitudes towards research when
a family member had ARD (Cohen's d=0.48). CONCLUSIONS: Principal components
analysis shows different dimensions of attitudes towards research engagement. The
different dimensions are related to community members' desire to be invited to
participate in research, awareness of past research in the community and having
been screened or diagnosed with a health condition related to the Superfund
contaminant.
PMID- 27507237
TI - Hypoxia Tolerance and Metabolic Suppression in Oxygen Minimum Zone Euphausiids:
Implications for Ocean Deoxygenation and Biogeochemical Cycles.
AB - The effects of regional variations in oxygen and temperature levels with depth
were assessed for the metabolism and hypoxia tolerance of dominant euphausiid
species. The physiological strategies employed by these species facilitate
prediction of changing vertical distributions with expanding oxygen minimum zones
and inform estimates of the contribution of vertically migrating species to
biogeochemical cycles. The migrating species from the Eastern Tropical Pacific
(ETP), Euphausia eximia and Nematoscelis gracilis, tolerate a Partial Pressure
(PO2) of 0.8 kPa at 10 degrees C (~15 uM O2) for at least 12 h without
mortality, while the California Current species, Nematoscelis difficilis, is
incapable of surviving even 2.4 kPa PO2 (~32 uM O2) for more than 3 h at that
temperature. Euphausia diomedeae from the Red Sea migrates into an intermediate
oxygen minimum zone, but one in which the temperature at depth remains near 22
degrees C. Euphausia diomedeae survived 1.6 kPa PO2 (~22 uM O2) at 22 degrees C
for the duration of six hour respiration experiments. Critical oxygen partial
pressures were estimated for each species, and, for E. eximia, measured via
oxygen consumption (2.1 kPa, 10 degrees C, n = 2) and lactate accumulation (1.1
kPa, 10 degrees C). A primary mechanism facilitating low oxygen tolerance is an
ability to dramatically reduce energy expenditure during daytime forays into low
oxygen waters. The ETP and Red Sea species reduced aerobic metabolism by more
than 50% during exposure to hypoxia. Anaerobic glycolytic energy production, as
indicated by whole-animal lactate accumulation, contributed only modestly to the
energy deficit. Thus, the total metabolic rate was suppressed by ~49-64%.
Metabolic suppression during diel migrations to depth reduces the metabolic
contribution of these species to vertical carbon and nitrogen flux (i.e., the
biological pump) by an equivalent amount. Growing evidence suggests that
metabolic suppression is a widespread strategy among migrating zooplankton in
oxygen minimum zones and may have important implications for the economy and
ecology of the oceans. The interacting effects of oxygen and temperature on the
metabolism of oceanic species facilitate predictions of changing vertical
distribution with climate change.
PMID- 27507238
TI - Hypoxia and Anoxia Tolerance in the Annual Killifish Austrofundulus limnaeus.
AB - Embryos of the annual killifish Austrofundulus limnaeus are routinely exposed to
oxygen limitation during development and are extremely tolerant of anoxia.
Importantly, tolerance of anoxia is not strictly associated with entrance into
metabolic dormancy associated with diapause II, but rather any embryo will
respond to anoxia by entering into a state of anoxia-induced quiescence. Hypoxia
causes a reduction in the rate of development, reduced heart rates, and reduced
capacities for metabolic enzyme activity in both aerobic and anaerobic pathways.
Embryos of A. limnaeus begin life as oxyconformers, and transition into
oxyregulators near the completion of embryonic development. As this transition
occurs, extreme anoxia tolerance is lost. The rate of early development is
independent of oxygen partial pressure, despite the fact that the embryos are
oxyconformers. This suggests a contribution from anaerobic pathways to support
early development. However, the specific pathways supporting this metabolism are
unknown. The response of A. limnaeus embryos to hypoxia and anoxia is unique
compared to other fishes and most other vertebrates, and thus future studies on
this species may lend insight into novel mechanisms that support survival during
prolonged oxygen limitation.
PMID- 27507236
TI - Counteracting Age-related Loss of Skeletal Muscle Mass: a clinical and
ethnological trial on the role of protein supplementation and training load (CALM
Intervention Study): study protocol for a randomized controlled trial.
AB - BACKGROUND: Aging is associated with decreased muscle mass and functional
capacity, which in turn decrease quality of life. The number of citizens over the
age of 65 years in the Western world will increase by 50 % over the next four
decades, and this demographic shift brings forth new challenges at both societal
and individual levels. Only a few longitudinal studies have been reported, but
whey protein supplementation seems to improve muscle mass and function, and its
combination with heavy strength training appears even more effective. However,
heavy resistance training may reduce adherence to training, thereby attenuating
the overall benefits of training. We hypothesize that light load resistance
training is more efficient when both adherence and physical improvement are
considered longitudinally. We launched the interdisciplinary project on
Counteracting Age-related Loss of Skeletal Muscle Mass (CALM) to investigate the
impact of lifestyle changes on physical and functional outcomes as well as
everyday practices and habits in a qualitative context. METHODS: We will
randomize 205 participants older than 65 years to be given 1 year of two daily
nutrient supplements with 10 g of sucrose and 20 g of either collagen protein,
carbohydrates, or whey. Further, two groups will perform either heavy progressive
resistance training or light load training on top of the whey supplement.
DISCUSSION: The primary outcome of the CALM Intervention Study is the change in
thigh cross-sectional area. Moreover, we will evaluate changes in physical
performance, muscle fiber type and acute anabolic response to whey protein
ingestion, sensory adaptation, gut microbiome, and a range of other measures,
combined with questionnaires on life quality and qualitative interviews with
selected subjects. The CALM Intervention Study will generate scientific evidence
and recommendations to counteract age-related loss of skeletal muscle mass in
elderly individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT02034760 .
Registered on 10 January 2014. ClinicalTrials.gov NCT02115698 . Registered on 14
April 2014. Danish regional committee of the Capital Region H-4-2013-070.
Registered on 4 July 2013. Danish Data Protection Agency 2012-58-0004 - BBH-2015
001 I-Suite 03432. Registered on 9 January 2015.
PMID- 27507239
TI - A novel blue-light phototropic response is revealed in roots of Arabidopsis
thaliana in microgravity.
AB - MAIN CONCLUSION: Blue-light positive phototropism in roots is masked by gravity
and revealed in conditions of microgravity. In addition, the magnitude of red
light positive phototropic curvature is correlated to the magnitude of gravity.
Due to their sessile nature, plants utilize environmental cues to grow and
respond to their surroundings. Two of these cues, light and gravity, play a
substantial role in plant orientation and directed growth movements (tropisms).
However, very little is currently known about the interaction between light-
(phototropic) and gravity (gravitropic)-mediated growth responses. Utilizing the
European Modular Cultivation System on board the International Space Station, we
investigated the interaction between phototropic and gravitropic responses in
three Arabidopsis thaliana genotypes, Landsberg wild type, as well as mutants of
phytochrome A and phytochrome B. Onboard centrifuges were used to create a
fractional gravity gradient ranging from reduced gravity up to 1g. A novel
positive blue-light phototropic response of roots was observed during conditions
of microgravity, and this response was attenuated at 0.1g. In addition, a red
light pretreatment of plants enhanced the magnitude of positive phototropic
curvature of roots in response to blue illumination. In addition, a positive
phototropic response of roots was observed when exposed to red light, and a
decrease in response was gradual and correlated with the increase in gravity. The
positive red-light phototropic curvature of hypocotyls when exposed to red light
was also confirmed. Both red-light and blue-light phototropic responses were also
shown to be affected by directional light intensity. To our knowledge, this is
the first characterization of a positive blue-light phototropic response in
Arabidopsis roots, as well as the first description of the relationship between
these phototropic responses in fractional or reduced gravities.
PMID- 27507240
TI - Climate change increases the risk of herbicide-resistant weeds due to enhanced
detoxification.
AB - MAIN CONCLUSION: Global warming will increase the incidence of metabolism-based
reduced herbicide efficacy on weeds and, therefore, the risk for evolution of non
target site herbicide resistance. Climate changes affect food security both
directly and indirectly. Weeds are the major biotic factor limiting crop
production worldwide, and herbicides are the most cost-effective way for weed
management. Processes associated with climatic changes, such as elevated
temperatures, can strongly affect weed control efficiency. Responses of several
grass weed populations to herbicides that inhibit acetyl-CoA carboxylase (ACCase)
were examined under different temperature regimes. We characterized the mechanism
of temperature-dependent sensitivity and the kinetics of pinoxaden
detoxification. The products of pinoxaden detoxification were quantified.
Decreased sensitivity to ACCase inhibitors was observed under elevated
temperatures. Pre-treatment with the cytochrome-P450 inhibitor malathion supports
a non-target site metabolism-based mechanism of herbicide resistance. The first
48 h after herbicide application were crucial for pinoxaden detoxification. The
levels of the inactive glucose-conjugated pinoxaden product (M5) were found
significantly higher under high- than low-temperature regime. Under high
temperature, a rapid elevation in the level of the intermediate metabolite (M4)
was found only in pinoxaden-resistant plants. Our results highlight the
quantitative nature of non-target-site resistance. To the best of our knowledge,
this is the first experimental evidence for temperature-dependent herbicide
sensitivity based on metabolic detoxification. These findings suggest an
increased risk for the evolution of herbicide-resistant weeds under predicted
climatic conditions.
PMID- 27507241
TI - CpG site methylation in CRYAA promoter affect transcription factor Sp1 binding in
human lens epithelial cells.
AB - BACKGROUND: Age-related cataract (ARC) is the leading cause of visual impairment
worldwide, and alpha-crystallin (CRYAA) is the predominant structural protein
involved in the maintenance of lens clarity and refractive properties. We
previously demonstrated that CRYAA genes undergo epigenetic repression in the
lens epithelia in ARC. We further analyze the underlying mechanism in the current
study. METHODS: The transcription factor binding sites of the CpG island of CRYAA
promoter were predicted by TESS website. An electrophoretic mobility shift assay
(EMSA) was used to analyze the impact of the methylation of CpG sites on
transcription factors. Human lens epithelial B-3 (HLE B-3) Cells were treated
with demethylation agent zebularine in the concentrations of 0 (PBS as control),
10 MUM, 20 MUM, 50 MUM, 100 MUM and 200 MUM, respectively. After treatment in the
above concentrations for 24 h, 48 h and 72 h, respectively, CRYAA mRNA expression
levels were detected by Quantitative Real-Time RT-PCR. RESULTS: The methylation
of the CpG site of the CRYAA promoter decreased the DNA-binding capacity of
transcription factor Sp1. Zebularine increased CRYAA expression in HLE B-3 Cells
in a dose- dependent and time- dependent pattern. CONCLUSIONS: The evidence
presented suggests that the methylation of the CpG sites of the CRYAA promotor
directly affect Sp1 binding, leading to down expression of CRYAA in human lens
epithelial cells. Zebularine treatment could restore CRYAA expression in a dose-
dependent and time- dependent pattern.
PMID- 27507242
TI - When the brain goes diving: transcriptome analysis reveals a reduced aerobic
energy metabolism and increased stress proteins in the seal brain.
AB - BACKGROUND: During long dives, the brain of whales and seals experiences a
reduced supply of oxygen (hypoxia). The brain neurons of the hooded seal
(Cystophora cristata) are more tolerant towards low-oxygen conditions than those
of mice, and also better survive other hypoxia-related stress conditions like a
reduction in glucose supply and high concentrations of lactate. Little is known
about the molecular mechanisms that support the hypoxia tolerance of the diving
brain. RESULTS: Here we employed RNA-seq to approach the molecular basis of the
unusual stress tolerance of the seal brain. An Illumina-generated transcriptome
of the visual cortex of the hooded seal was compared with that of the ferret
(Mustela putorius furo), which served as a terrestrial relative. Gene ontology
analyses showed a significant enrichment of transcripts related to translation
and aerobic energy production in the ferret but not in the seal brain. Clusterin,
an extracellular chaperone, is the most highly expressed gene in the seal brain
and fourfold higher than in the ferret or any other mammalian brain
transcriptome. The largest difference was found for S100B, a calcium-binding
stress protein with pleiotropic function, which was 38-fold enriched in the seal
brain. Notably, significant enrichment of S100B mRNA was also found in the
transcriptomes of whale brains, but not in the brains of terrestrial mammals.
CONCLUSION: Comparative transcriptomics indicates a lower aerobic capacity of the
seal brain, which may be interpreted as a general energy saving strategy.
Elevated expression of stress-related genes, such as clusterin and S100B,
possibly contributes to the remarkable hypoxia tolerance of the brain of the
hooded seal. Moreover, high levels of S100B that possibly protect the brain
appear to be the result of the convergent adaptation of diving mammals.
PMID- 27507243
TI - Gender Differences in Perceived Unmet Treatment Needs Among Persons With and
Without Co-occurring Disorders.
AB - This study examined gender differences in perceived unmet treatment needs among
persons with and without co-occurring substance use disorders and serious mental
health conditions. Data were drawn from the 2008-2013 National Survey on Drug Use
and Health (unweighted N = 37,187) to test the hypothesis that the relationships
between diagnosis and perceived unmet treatment needs differ as a function of
gender. Compared to individuals with a substance use disorder or severe mental
illness, those with co-occurring disorders were more likely to report perceived
unmet needs for substance abuse and mental health treatment. Gender significantly
moderated the relationship between diagnosis and unmet needs, suggesting that men
with co-occurring disorders might be more adversely affected. Findings highlight
the need for better understanding of gender-diagnosis differences with respect to
unmet needs for substance abuse and mental health care.
PMID- 27507244
TI - Overexpression of jumu induces melanotic nodules by activating Toll signaling in
Drosophila.
AB - Melanotic nodules are commonly assumed to be caused by an abnormal immune
response. Several hematopoietic mutants and signaling pathways, including the
Toll, JAK/STAT, Ras and JNK pathways, can cause melanotic nodules to develop when
specifically activated in hemocytes. Here, we used the UAS-Gal4 system to
overexpress jumeaux (jumu) in the fly immune response system. Jumeaux (Jumu) is a
new member of the winged-helix/forkhead (WH/FKH) gene family of transcription
factors, which plays an important role in the growth and morphogenesis of
Drosophila and participates in the proliferation and differentiation of
hemocytes. Overexpressing jumu in both hemocytes and the fat body generated many
melanotic nodules in larvae and adult flies. The nodules observed in the fat body
were surrounded by large numbers of blood cells through a process that appeared
similar to foreign body encapsulation. This phenomenon is caused by Toll pathway
activation and leads to blood cells deposited in the fat body. In addition, we
also report the dissociation of fat cells and the abnormal proliferation and
differentiation of blood cells. These results suggest a Jumu-mediated crosstalk
between hematopoiesis and the fat body, especially during the Toll-dependent
formation of melanotic nodules.
PMID- 27507245
TI - 21-Gene recurrence score decreases receipt of chemotherapy in ER+ early-stage
breast cancer: an analysis of the NCDB 2010-2013.
AB - The purpose of this study was to determine if receipt of chemotherapy was
associated with utilization of the 21-gene recurrence score assay (RS assay) or
with recurrence score (RS) in eligible patients. Using the National Cancer Data
Base (NCDB), we identified female patients eligible for RS assay based on
National Comprehensive Cancer Network (NCCN) guidelines: age 18-70, ER-positive
and HER2-negative early-stage breast cancer diagnosed during 2010-2013. We
excluded patients not meeting testing guidelines. Inclusion required result of RS
in patients who underwent RS assay and status for receipt of chemotherapy.
Multivariable logistic regression models and propensity matched analysis were
used to determine associations between RS assay and RS with receipt of
chemotherapy. Among 129,765 patients who were eligible, 74,778 underwent RS assay
and had results available. Of these, 59.5 % (44,505) had low-risk, 32.0 %
(23,920) had intermediate-risk, and 8.5 % (6353) had high-risk RS. Patients with
intermediate- and high-risk RS were more likely to receive chemotherapy [OR 12.9
(CI 12.2-13.6), p <0.001 and OR 87.2 (CI 79.6-95.6), p <0.0001], respectively. In
both low- and intermediate-risk groups, increasing RS score was significantly
associated with increasing odds of receiving chemotherapy [OR 1.10 (CI 1.09
1.12), p <0.0001 and OR 1.26 (CI 1.25-1.27), p <0.0001, respectively, for each
point increase in RS]. Receipt of chemotherapy was more likely in patients who
did not undergo RS assay compared to those who did, OR 1.21 (CI 1.175-1.249) p
<0.0001. The utilization of RS assay and the RS were both strongly associated
with chemotherapy receipt. Patients eligible for chemotherapy, based on NCCN
criteria, were more likely to receive chemotherapy if they did not undergo RS
assay or they had a high RS.
PMID- 27507246
TI - Tyrosine kinase inhibition reverses TDP-43 effects on synaptic protein
expression, astrocytic function and amino acid dis-homeostasis.
AB - The trans-activating response of DNA/RNA-binding protein (TDP)-43 pathology is
associated with many neurodegenerative diseases via unknown mechanisms. Here, we
use a transgenic mouse model over-expressing human wild-type neuronal TDP-43 to
study the effects of TDP-43 pathology on glutamate metabolism and synaptic
function. We found that neuronal TDP-43 over-expression affects synaptic protein
expression, including Synapsin I, and alters surrounding astrocytic function. TDP
43 over-expression is associated with an increase in glutamate and gamma-amino
butyric acid and reduction of glutamine and aspartate levels, indicating
impairment of presynaptic terminal. TDP-43 also decreases tricarboxylic acid
cycle metabolism and induces oxidative stress via lactate accumulation. Neuronal
TDP-43 does not alter microglia activity or significantly changes systemic and
brain inflammatory markers compared to control. We previously demonstrated that
brain-penetrant tyrosine kinase inhibitors (TKIs), nilotinib and bosutinib,
reduce TDP-43-induced cell death in transgenic mice. Here, we show that TKIs
reverse the effects of TDP-43 on synaptic proteins, increase astrocytic function
and restore glutamate and neurotransmitter balance in TDP-43 mice. Nilotinib, but
not bosutinib, reverses mitochondrial impairment and oxidative metabolism. Taken
together, these data suggest that TKIs can attenuate TDP-43 toxicity and improve
synaptic and astrocytic function, independent of microglial or other inflammatory
effects. In conclusion, our data demonstrate novel mechanisms of the effects of
neuronal TDP-43 over-expression on synaptic protein expression and alteration of
astrocytic function.
PMID- 27507247
TI - The Power of Being Vulnerable in Christian Soul Care: Common Humanity and
Humility.
AB - Soul caregivers often hesitate to be vulnerable in their pastoral practices.
Jesus, however, embraced his vulnerabilities as a human to redeem humanity even
though he was the Son of God. This paper first explores the dynamics of shame and
power that make soul caregivers reluctant to accept their vulnerabilities and
then describes the contributions of sharing caregiver's vulnerabilities in a soul
care practice. This article argues that being vulnerable allows a soul caregiver
to imitate Jesus by sharing in the client's common humanity, initiating an
authentic relationship between the client and the soul caregiver; it is also a
practice of humility, inviting God's cure in soul care. This study proposes the
necessity of embracing vulnerability in soul care ministry, instead of hiding it.
PMID- 27507248
TI - Prediction of Quantum Anomalous Hall Insulator in half-fluorinated GaBi
Honeycomb.
AB - Using first-principles electronic structure calculations, we predict half
fluorinated GaBi honeycomb under tensile strain to harbor a quantum anomalous
Hall (QAH) insulator phase. We show that this QAH phase is driven by a single
inversion in the band structure at the Gamma point. Moreover, we have computed
the electronic spectrum of a half-fluorinated GaBi nanoribbon with zigzag edges,
which shows that only one edge band crosses the Fermi level within the band gap.
Our results suggest that half-fluorination of the GaBi honeycomb under tensile
strain could provide a new platform for developing novel spintronics devices
based on the QAH effect.
PMID- 27507249
TI - Interventions to improve the rate or timing of initiation of antiretroviral
therapy for HIV in sub-Saharan Africa: meta-analyses of effectiveness.
AB - INTRODUCTION: As global policy evolves toward initiating lifelong antiretroviral
therapy (ART) regardless of CD4 count, initiating individuals newly diagnosed
with HIV on ART as efficiently as possible will become increasingly important. To
inform progress, we conducted a systematic review of pre-ART interventions aiming
to increase ART initiation in sub-Saharan Africa. METHODS: We searched PubMed,
Embase and the ISI Web of Knowledge from 1 January 2008 to 1 March 2015, extended
in PubMed to 25 May 2016, for English language publications pertaining to any
country in sub-Saharan Africa and reporting on general adult populations. We
included studies describing interventions aimed at increasing linkage to HIV
care, retention in pre-ART or uptake of ART, which reported ART initiation as an
outcome. We synthesized the evidence on causal intervention effects in meta
analysis of studies belonging to distinct intervention categories. RESULTS AND
DISCUSSION: We identified 22 studies, which evaluated 25 interventions and
included data on 45,393 individual patients. Twelve of twenty-two studies were
observational. Rapid/point-of-care (POC) CD4 count technology (seven
interventions) (relative risk, RR: 1.26; 95% confidence interval, CI: 1.02-1.55),
interventions within home-based testing (two interventions) (RR: 2.00; 95% CI:
1.36-2.92), improved clinic operations (three interventions) (RR: 1.36; 95% CI:
1.25-1.48) and a package of patient-directed services (three interventions) (RR:
1.54; 95% CI: 1.20-1.97) were all associated with increased ART initiation as was
HIV/TB service integration (three interventions) (RR: 2.05; 95% CI: 0.59-7.09)
but with high imprecision. Provider-initiated testing (three interventions) was
associated with reduced ART initiation (RR: 0.91; 95% CI: 0.86-0.97). Counselling
and support interventions (two interventions) (RR 1.08; 95% CI: 0.94-1.26) had no
impact on ART initiation. Overall, the evidence was graded as low or moderate
quality using the GRADE criteria. CONCLUSIONS: The literature on interventions to
increase uptake of ART is limited and of mixed quality. POC CD4 count and
improving clinic operations show promise. More implementation research and
evaluation is needed to identify how best to offer treatment initiation in a
manner that is both efficient for service providers and effective for patients
without jeopardizing treatment outcomes.
PMID- 27507250
TI - The evaluation of a healthcare passport to improve quality of care and
communication for people living with dementia (EQuIP): a protocol paper for a
qualitative, longitudinal study.
AB - BACKGROUND: There is an urgent need for the development of simple communication
tools that convey the strengths, assets, and healthcare needs of people living
with dementia. A Healthcare Passport may improve communication with range of
health and social support services, enhancing quality and continuity of care, and
to permit a consideration of the challenges and how these might be managed
effectively and compassionately. This study aims to evaluate the acceptability
and use of this type of intervention for people living with dementia and their
carers. METHODS/DESIGN: This is a qualitative longitudinal study informed by a
critical realist review. The participants will be individuals identified as
having mild-moderate dementia and informal carers. The in-depth interviews will
occur at three points over the course of 18 months as they use the passport. This
will be supplemented by analysis of the content of the passports and information
from health and social care providers on the daily practicalities of using the
passport in a range of healthcare settings. DISCUSSION: By using a critical
realist review and a qualitative, longitudinal approach, the study allows for the
assessment of a complex intervention in a manner which goes beyond evaluating the
basic efficacy of the passport, but looking more deeply at how it worked, for
whom, and in what context. It has the potential to develop new data on how
interventions improve communication across a range of service providers, while
encouraging health and social care professionals to respect and encourage the
development of self-management and retention of personhood throughout the
progression of life-limiting illnesses.
PMID- 27507251
TI - Rifaximin for the prevention of readmissions for patients with hepatic
encephalopathy - the price is right.
PMID- 27507252
TI - Nonselective beta blockers in patients with ascites: implications of a nationwide
study.
PMID- 27507253
TI - Response to Successful liver transplantation for hepatocellular carcinoma
following down-staging using sorafenib single therapy by Borentain et al.
PMID- 27507254
TI - Surgical spacer placement prior carbon ion radiotherapy (CIRT): an effective
feasible strategy to improve the treatment for sacral chordoma.
AB - BACKGROUND: Sacral chordoma (SC) is a neoplasm arising from residual notochordal
cells degeneration. SC is difficult to manage mainly because of anatomic location
and tendency to extensive spread. Carbon ion radiotherapy (CIRT) is highly
precise to selectively deliver high biological effective dose to the tumor target
sparing the anatomical structure on its path even if when SC is contiguous to the
intestine, and a surgical spacer might be an advantageous tool to create a
distance around the target volume allowing radical curative dose delivery with a
safe dose gradient to the surrounding organs. This paper describes a double
approach-open and hand-assisted laparoscopic-for a silicon spacer placement in
patients affected by sacral chordoma undergoing carbon ion radiotherapy. METHODS:
Six consecutive patients have been enrolled for surgical spacer placement-open
(three) or hand-assisted (three)-prior carbon ion radiotherapy treatment in order
to increase efficacy of carbon ion radiotherapy minimizing its side effects.
RESULTS: Results showed that silicon spacer placement for SC treatment is
feasible both via laparoscopic and laparotomic approach. CONCLUSIONS: Its use
might improve CIRT safety and thus efficacy for SC treatment.
PMID- 27507255
TI - Differentiation and description of aromatic short grain rice landraces of eastern
Indian state of Odisha based on qualitative phenotypic descriptors.
AB - BACKGROUND: Speciality rice, in general, and aromatic rice in particular, possess
enormous market potential for enhancing farm profits. However, systematic
characterization of the diversity present in this natural wealth is a major pre
requisite for using it in the breeding programs. This study reports qualitative
phenotypic trait based characterization of 126 short grain aromatic rice
genotypes, collected from different areas of the state of Odisha, India. RESULTS:
Out of the 24 descriptors employed, highest variability (8 different types) was
observed for lemma-palea colour with a genetic diversity index (He) of 0.696. The
principal component analysis reveals that the tip colour of lemma, colour of awn
and colour of stigma, cumulatively explain 74 % of the total variation. The
Population STRUCTURE analysis classified the population into two subpopulations
which were subdivided further into four distinct groups. The western and southern
districts of Odisha are endowed with maximum diversity in comparison to eastern
and northern districts and at district level comparisons, Koraput and Puri
districts are rich with a genetic diversity values of 0.324 and 0.303
respectively. With this set of morphological qualitative traits, based on
'phenoprinting', a newly proposed bar coding system, unique fingerprints of each
genotype can be effectively generated that can help in easy identification of
these genotypes. CONCLUSION: Though aromatic rices represent a tiny fraction of
the total rice germplasm, a small collection of 126 land races did exhibit rich
diversity for all the qualitative traits. For lemma-palea colour, eight different
types were detected while for tip colour of lemma, six different types were
recorded, suggesting the presence of rich variability in short grain aromatic
rices that are conserved in this region. The proposed 'phenoprinting' can be an
effective descriptor with the unique finger prints generated for each genotype
and coupled with molecular (DNA) finger printing, we can discriminate and
identify each and every aromatic short grain rice genotype. The proposed system
not only help in conservation but also can confer IPR protection to these
specialty rices.
PMID- 27507256
TI - Comparison of Updated Weight and Height Percentiles with Previous References in 6
17-Year-Old Children in Kayseri, Turkey.
AB - OBJECTIVE: To compare updated weight and height percentiles of 6-17-year-old
children from all socio-economic levels in Kayseri with previous local references
and other national/international data. METHODS: The second study "Determination
of Anthropometric Measurements of Turkish Children and Adolescents study (DAMTCA
II)" was conducted in Kayseri, between October 2007 and April 2008. Weight and
height measurements from 4321 (1926 boys, 2395 girls) school children aged
between 6 to 17 years were included in this cross-sectional study. Using these
data, weight and height percentile curves were produced with generalized additive
models for location, scale and shape (GAMLSS) and compared with the most recent
references. RESULTS: Smoothed percentile curves including the 3rd, 5th, 10th,
15th, 25th, 50th, 75th, 85th, 90th, 95th, and 97th percentiles were obtained for
boys and girls. These results were compared with DAMTCA I study and with two
national (Istanbul and Ankara) and international data from Asia and from Europe.
CONCLUSION: This study provides updated weight and height references for Turkish
school children aged between 6 and 17 years residing in Kayseri.
PMID- 27507257
TI - On characterizing protein spatial clusters with correlation approaches.
AB - Spatial aggregation of proteins might have functional importance, e.g., in
signaling, and nano-imaging can be used to study them. Such studies require
accurate characterization of clusters based on noisy data. A set of spatial
correlation approaches free of underlying cluster processes and input parameters
have been widely used for this purpose. They include the radius of maximal
aggregation ra obtained from Ripley's L(r) - r function as an estimator of
cluster size, and the estimation of various cluster parameters based on an
exponential model of the Pair Correlation Function(PCF). While convenient, the
accuracy of these methods is not clear: e.g., does it depend on how the molecules
are distributed within the clusters, or on cluster parameters? We analyze these
methods for a variety of cluster models. We find that ra relates to true cluster
size by a factor that is nonlinearly dependent on parameters and that can be
arbitrarily large. For the PCF method, for the models analyzed, we obtain linear
relationships between the estimators and true parameters, and the estimators were
found to be within +/-100% of true parameters, depending on the model. Our
results, based on an extendable general framework, point to the need for caution
in applying these methods.
PMID- 27507258
TI - The role of ICT in nursing practice: an integrative literature review of the
Swedish context.
AB - BACKGROUND: The Swedish healthcare system employs information and communication
technologies (ICT) in nursing practice to meet quality-, security- and efficiency
related demands. Although ICT is integrated with nursing practices, nurses do not
always feel that they are convenient to use it. We need to improve our knowledge
of the role of ICT in healthcare environments and so we decided to complement
existing experience of how ICT influences nursing practice. AIM: This study aimed
to review and synthesise the available literature on the role of ICT in nursing
practice in Swedish healthcare settings. METHOD: To consolidate previous studies
based on diverse methodologies, an integrative literature review was carried out.
Three databases were used to search for literature, 20 articles met the inclusion
criteria. RESULTS: The literature review indicates that ICT integration into
nursing practice is a complex process that impacts nurses' communication and
relationships in patient care, working conditions, and professional identities
and development. Nurses are found to express ambiguous views on ICT as a usable
service in their everyday practice since it impacts both positively and
negatively. DISCUSSION AND CONCLUSION: Although ICT cannot replace physical
presence, it can be considered a complementary service that gives rise to
improved patient care. However, nonverbal communication cues may be missed when
ICT is used as mediating tool and ICT can be limiting because it is not always
designed to meet nurse and patient needs. The meaning of an encounter appears to
change when ICT is used in nursing practice, not only for patient relationships
but also for interpersonal communication.
PMID- 27507259
TI - Anti-CCP status determines the power Doppler oscillation pattern in rheumatoid
arthritis: a prospective study.
AB - Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint
destruction. Serologically, it can be differentiated according to rheumatoid
factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), or both.
This differentiation is prognostically and therapeutically relevant. No method
has been described to separate the two forms phenotypically. We hypothesize that
a differentiation is possible by evaluating oscillation patterns in power Doppler
sonography (PDS). In a prospective study, 20 patients with anti-CCP-positive RA
and 20 patients with anti-CCP-negative RA with active wrist synovitis were
examined. A PDS scan was performed, and perfusion maxima (P max) and minima (P
min) as well as the amplitude (DeltaP) were determined by a blinded study member.
The amplitude was standardized (sDeltaP) by dividing by P max, and the anti-CCP
positive and anti-CCP-negative patients as well as the RF-positive and RF
negative were compared to each other. In the ultrasonographic evaluation, we
found a highly significant difference in sDeltaP between CCPp and CCPn patients
(median 19.0 vs. 42.9 %, p < 0.0001). sDeltaP is independent of disease activity.
The absolute amplitude DeltaP did not differ between the groups. Also, in anti
CCP-positive patients there was a completely linear correlation between P max and
P min, and this was far less marked in anti-CCP-negative patients. Anti-CCP
positive and anti-CCP-negative RA display different PDS oscillation patterns.
This constitutes a nonserological parameter to differentiate between the two
forms. The difference in PDS oscillation patterns suggests that the underlying
pathological process differs between the forms.
PMID- 27507260
TI - Needs of adolescents and young adults after cancer treatment: a systematic
review.
AB - The aim of this study was to conduct a systematic review of the literature on the
needs of adolescents and young adults (AYAs) who have survived cancer. PRISMA
recommendations for systematic reviews were followed, and the quality of the
studies reviewed was also assessed with a specific checklist. The following
databases were searched from their inception to May 2016: ERIC, EMBASE, MEDLINE,
PILOTS, ProQuest, PsycARTICLES, PsycBOOKS, psycCRITIQUES, PsycINFO, Social
Services Abstracts and Sociological Abstracts. Fourteen studies were identified
and analysed. The results show that the most common needs for AYA cancer
survivors are as follows: "individualised information and advice," "counselling
and psychological support" and "social support, and social relationships." These
results are different from those reported in studies on adults, which shows the
importance of specifically addressing the needs of this population. In order to
advance in this emerging area of study and facilitate the work of health
professionals, it is crucial to reach a consensus on two central issues: how the
needs of AYA survivors should be conceptualised and what the most valid and
reliable procedure for assessing patient's needs is.
PMID- 27507262
TI - An Exploration of the Interaction Between Touch Avoidance and the Pleasant Touch
(C-Tactile Afferent) System.
AB - C-tactile (CT) afferent fibers are optimally stimulated by slow gentle stroking,
and an inverted U-shaped relationship exists between stroking velocity and
pleasantness ratings of this type of touch. This study investigated whether an
additional and potentially important variable, touch avoidance, interacts with
this relationship. While a typical U-shaped velocity-pleasantness relationship
was expected, those high in touch avoidance were expected to rate CT-targeted
touch (1-10 cm/s) as less pleasant than those low in touch avoidance. Thirty-five
participants rated the pleasantness of a brush stroked across their forearm at
five velocities (0.3, 1, 3, 10, 30 cm/s) administered by a custom-built touch
stimulator ("the touch device"). Participants also completed two self-report
measures of touch avoidance. There was an inverted U-shaped relationship between
velocity and pleasantness ratings, and high touch avoidance resulted in a
downward shift of this curve. The downward shift was across all velocities,
including those that do not maximally engage CT afferents. It appears that touch
avoidance reduces the pleasantness of all kinds of touch in a similar way, and it
is unlikely to be specifically related to CT afferent functioning. Other
potential mechanisms leading to touch avoidance are discussed.
PMID- 27507261
TI - Overweight/obese status associates with favorable outcome in patients with
metastatic nasopharyngeal carcinoma: a 10-year retrospective study.
AB - BACKGROUND: Although the prognostic impact of body mass index (BMI) in patients
with non-metastatic nasopharyngeal carcinoma (NPC) had been extensively studied,
its effect among metastatic NPC patients remains unknown. The purpose of this
study was to evaluate the prognostic effect of BMI in patients with metastatic
NPC. METHODS: We retrospectively studied 819 patients who were diagnosed with
distant metastasis from NPC and received treatment between 1998 and 2007. The
patients were divided into three subgroups according to the World Health
Organization classifications for Asian populations: underweight (BMI <18.5
kg/m(2)), normal weight (BMI 18.5-22.9 kg/m(2)), and overweight/obese (BMI >=23.0
kg/m(2)). The associations of BMI with overall survival (OS) and progression-free
survival (PFS) were determined by Cox regression analysis. RESULTS: Of the 819
patients, 168 (20.5%) were underweight, 431 (52.6%) were normal weight, and 220
(26.9%) were overweight/obese. Multivariate analysis adjusted for covariates
showed that overweight/obese patients had a longer OS than underweight patients
[hazard ratio (HR), 0.64; 95% confidence interval (CI), 0.49-0.84] and normal
weight patients (HR, 0.72; 95% CI, 0.57-0.90); no significant difference in PFS
was observed among these three groups (P = 0.407). Moreover, in stratified
analysis, no statistically significant differences in the effect of
overweight/obese status among different subgroups were observed. CONCLUSION: For
patients with metastatic NPC, overweight/obese status was associated with longer
OS but not longer PFS compared with underweight or normal weight status.
PMID- 27507263
TI - Aging and the Haptic Perception of Material Properties.
AB - The ability of 26 younger (mean age was 22.5 years) and older adults (mean age
was 72.6 years) to haptically perceive material properties was evaluated. The
participants manually explored (for 5 seconds) 42 surfaces twice and placed each
of these 84 experimental stimuli into one of seven categories: paper, plastic,
metal, wood, stone, fabric, and fur/leather. In general, the participants were
best able to identify fur/leather and wood materials; in contrast, recognition
performance was worst for stone and paper. Despite similar overall patterns of
performance for younger and older participants, the younger adults' recognition
accuracies were 26.5% higher. The participants' tactile acuities (assessed by
tactile grating orientation discrimination) affected their ability to identify
surface material. In particular, the Pearson r correlation coefficient relating
the participants' grating orientation thresholds and their material
identification performance was -0.8: The higher the participants' thresholds, the
lower the material recognition ability. While older adults are able to
effectively perceive the solid shape of environmental objects using the sense of
touch, their ability to perceive surface materials is significantly compromised.
PMID- 27507265
TI - The Feasibility of an eLearning Nutrition Education Program for Low-Income
Individuals.
AB - BACKGROUND: Online eLearning may be an innovative, efficient, and cost-effective
method of providing nutrition education to a diverse low-income audience. AIMS:
The intent of this project is to examine perceptions of nutrition educators
regarding the feasibility of an eLearning nutrition education program tailored to
low-income Georgians. METHOD: Semistructured individual interviews were
conducted, guided by the constructivist theory. The interview guide focused on
three themes: accessibility, literacy, and content. A prototype of the program
also served as a talking point. Interviews were conducted in two urban Georgian
counties in a location chosen by each participant. We recruited a convenience
sample of Georgian nutrition educators ( n = 10, 100% female, 50% Black).
Interviews were transcribed and analyzed using constant comparative method.
RESULTS AND DISCUSSION: Motivation is considered the primary barrier to program
feasibility. Neither access to the Internet nor literacy are considered
significant barriers. Inclusion of skill-based, visual education methods such as
cooking videos, recipes, and step-by-step teaching tools was highlighted.
Nutrition educators perceived this program would be a feasible form of nutrition
education for the priority audience. CONCLUSIONS: Findings from this study will
inform the user-centered development of the program.
PMID- 27507264
TI - Symbiosis with Francisella tularensis provides resistance to pathogens in the
silkworm.
AB - Francisella tularensis, the causative agent of tularemia, is a highly virulent
facultative intracellular pathogen found in a wide range of animals, including
arthropods, and environments. This bacterium has been known for over 100 years,
but the lifestyle of F. tularensis in natural reservoirs remains largely unknown.
Thus, we established a novel natural host model for F. tularensis using the
silkworm (Bombyx mori), which is an insect model for infection by pathogens. F.
tularensis established a symbiosis with silkworms, and bacteria were observed in
the hemolymph. After infection with F. tularensis, the induction of melanization
and nodulation, which are immune responses to bacterial infection, were inhibited
in silkworms. Pre-inoculation of silkworms with F. tularensis enhanced the
expression of antimicrobial peptides and resistance to infection by pathogenic
bacteria. These results suggest that silkworms acquire host resistance via their
symbiosis with F. tularensis, which may have important fitness benefits in
natural reservoirs.
PMID- 27507266
TI - In silico analyses of mitochondrial ORFans in freshwater mussels (Bivalvia:
Unionoida) provide a framework for future studies of their origin and function.
AB - BACKGROUND: Many species of bivalves exhibit a unique system of mtDNA
transmission named Doubly Uniparental Inheritance (DUI). Under this system,
species have two distinct, sex-linked mitochondrial genomes: the M-type mtDNA,
which is transmitted by males to male offspring and found in spermatozoa, and the
F-type mtDNA, which is transmitted by females to all offspring, and found in all
tissues of females and in somatic tissues of males. Bivalves with DUI also have
sex-specific mitochondrial ORFan genes, (M-orf in the M mtDNA, F-orf in the F
mtDNA), which are open reading frames having no detectable homology and no known
function. DUI ORFan proteins have previously been characterized in silico in a
taxonomically broad array of bivalves including four mytiloid, one veneroid and
one unionoid species. However, the large evolutionary distance among these taxa
prevented a meaningful comparison of ORFan properties among these divergent
lineages. The present in silico study focuses on a suite of more closely-related
Unionoid freshwater mussel species to provide more reliably interpretable
information on patterns of conservation and properties of DUI ORFans. Unionoid
species typically have separate sexes, but hermaphroditism also occurs, and
hermaphroditic species lack the M-type mtDNA and possess a highly mutated version
of the F-orf in their maternally transmitted mtDNA (named H-orf in these taxa).
In this study, H-orfs and their respective proteins are analysed for the first
time. RESULTS: Despite a rapid rate of evolution, strong structural and
functional similarities were found for M-ORF proteins compared among species, and
among the F-ORF and H-ORF proteins across the studied species. In silico analyses
suggest that M-ORFs have a role in transport and cellular processes such as
signalling, cell cycle and division, and cytoskeleton organisation, and that F
ORFs may be involved in cellular traffic and transport, and in immune response. H
ORFs appear to be structural glycoproteins, which may be involved in signalling,
transport and transcription. Our results also support either a viral or a
mitochondrial origin for the ORFans. CONCLUSIONS: Our findings reveal striking
structural and functional similarities among proteins encoded by mitochondrial
ORFans in freshwater mussels, and strongly support a role for these genes in the
DUI mechanism. Our analyses also support the possibility of DUI systems with
elements of different sources/origins and different mechanisms of action in the
distantly-related DUI taxa. Parallel situations to the novel mitochondrially
encoded functions of freshwater mussel ORFans present in some other eukaryotes
are also discussed.
PMID- 27507267
TI - Epidemiology of hepatitis C virus in Ghana: a systematic review and meta
analysis.
AB - BACKGROUND: To fully understand the burden of hepatitis C (HCV) infection in
Ghana towards informing appropriate preventive measures, accurate prevalence
estimates are needed. In this study, we estimate the prevalence of chronic HCV
infection by systematically reviewing primary studies published between 1995 and
2015. METHODS: A systematic review and meta-analysis was conducted as per the
PRISMA guidelines. Comprehensive searches for hepatitis C prevalence studies for
the years 1995-2015 were conducted in PubMed, ScienceDirect, Google Scholar,
Africa Journals Online (AJOL) and the WHO African Index Medicus databases. We
also searched the websites of the ministry of health and Ghana Health service for
non-indexed studies or reports on the subject. Further systematic reference
screening of published reviews and retrieved studies were also conducted to
identify additional publications not captured through the online searches.
RESULTS: Twenty-Four (24) studies from nine regions of Ghana with a combined
sample size of 100,782 were analyzed. No study involving participants from Upper
West region was retrieved. The national prevalence of chronic HCV was estimated
as 3.0 % (95 % CI = 2.6 % to 3.5 %; I(2) = 97.61 %, p < 0. 001). Prevalence rates
of chronic HCV infection among blood donors was 2.6 % (95 % CI = 2.1 % to 3.1 %;
I(2) = 98.33 %, p < 0.001) with higher prevalence rate estimated for replacement
blood donors (RBDs) than voluntary blood donors (RBDs). Among pregnant women and
parturients, anti-HCV seroprevalence was estimated as 4.6 % (95 % CI = 1.8 % to
7.5 %; I(2) = 75.74 %, p = 0.016). The national prevalence of HIV/HCV co
infection was also estimated as 2.8 % (95 % CI = 0.4-6 %; I(2) = 65.86 %, p =
0.0053). Regional prevalence of chronic HCV infection were determined for Ashanti
(1.5 %, 95 % CI = 1.2 % to 1.9 %; I(2) = 96.24 %, p < 0.001) and Greater Accra
(6.4 %, 95 % CI = 4.2 % to 8.6 %; I(2) = I(2) = 88.5 %, P < 0. 001) regions but
no estimates were available for the other eight regions. The ascending order of
HCV prevalence rates according to years in which studies were conducted was 2006
2010 < 2011-2015 < 1995-2002 < 2001-2005. Higher prevalence of chronic HCV
infection was estimated for rural (5.7; 95 % CI 5.0-6.3 %; I(2) = 0, p = 0.804)
than urban (2.6 %, 95 % CI = 2.1 % to 3.0 %; I(2) = 97.3 %, p = 0.0001) settings.
CONCLUSION: Our study demonstrates a high prevalence of chronic hepatitis C
infection in Ghana. This highlights the urgent need for stronger commitments from
government and all stakeholders within the country to outline efficient
preventive and curative measures towards reducing the overall burden of the
disease.
PMID- 27507269
TI - Effect of Hippophae rhamnoides Extract on Oxidative Oropharyngeal Mucosal Damage
Induced in Rats Using Methotrexate.
AB - OBJECTIVES: The objective of this study is to investigate and evaluate the effect
of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats
with methotrexate (MTX) through biochemical, gene expression, and
histopathological examinations. METHODS: Experimental animals were divided into a
healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group
that received MTX (MTXG). The HREM and HREG groups of rats was administered 50
mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled
water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a
dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This
procedure was repeated for 1 month. At the end of this period, all of the animals
were sacrificed with a high dose of anesthesia. Then, the amounts of
malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed
oropharyngeal tissues. Interleukin-1beta (IL-1beta) and tumor necrosis factor
alpha (TNF-alpha) gene expressions were measured, and all the tissues were
studied histopathologically. RESULTS: The amount of MDA was significantly
increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001).
MTX significantly decreased the amount of tGSH in the MTXG group compared to the
HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers
in the animal group in which the levels of MDA, IL-1beta, and TNF-alpha were high
and the level of tGSH was low. However, histopathologic examination revealed
mucin pools in wide areas due to ruptured oropharynx glands, and proliferated,
dilated, and congested blood vessels and dilated ductal structures in some areas.
CONCLUSION: HRE protected oropharyngeal oxidative damage induced by MTX. As an
inexpensive and natural product, HRE has important advantages in the prevention
of oropharyngeal damage induced by MTX.
PMID- 27507270
TI - A Trainable Hearing Aid Algorithm Reflecting Individual Preferences for Degree of
Noise-Suppression, Input Sound Level, and Listening Situation.
AB - OBJECTIVES: In an effort to improve hearing aid users' satisfaction, recent
studies on trainable hearing aids have attempted to implement one or two
environmental factors into training. However, it would be more beneficial to
train the device based on the owner's personal preferences in a more expanded
environmental acoustic conditions. Our study aimed at developing a trainable
hearing aid algorithm that can reflect the user's individual preferences in a
more extensive environmental acoustic conditions (ambient sound level, listening
situation, and degree of noise suppression) and evaluated the perceptual benefit
of the proposed algorithm. METHODS: Ten normal hearing subjects participated in
this study. Each subjects trained the algorithm to their personal preference and
the trained data was used to record test sounds in three different settings to be
utilized to evaluate the perceptual benefit of the proposed algorithm by
performing the Comparison Mean Opinion Score test. RESULTS: Statistical analysis
revealed that of the 10 subjects, four showed significant differences in
amplification constant settings between the noise-only and speech-in-noise
situation (P<0.05) and one subject also showed significant difference between the
speech-only and speech-in-noise situation (P<0.05). Additionally, every subject
preferred different beta settings for beamforming in all different input sound
levels. CONCLUSION: The positive findings from this study suggested that the
proposed algorithm has potential to improve hearing aid users' personal
satisfaction under various ambient situations.
PMID- 27507271
TI - Purification of Two Novel Sugar Acid-binding Lectins from Haplomitrium Mnioides
(bryophyte, Plantae) and their Preliminary Characterization.
AB - Two novel sugar acid-binding lectins were purified from Haplomitrium mnioides
(Lindb.) Schust. using a procedure consisting of ammonium sulfate precipitation,
G-50 gel filtration, hydroxyapatite chromatography, and HW-50 gel filtration. We
reported their partial physicochemical properties: molecular weight, affinity for
carbohydrates and organic acids, pH stability, and dependence of their
hemagglutination activity on metal ions. We also determined their N-terminal
amino acid sequences. H. mnioides lectins (HMLs) were monomers (one with a
molecular weight of approximately 27 kDa, and the other with a molecular weight
of approximately 105 kDa) under both nonreducing and reducing conditions. They
were named HML27 and HML105, respectively. Both HMLs had an affinity for N
acetylneuraminic acid, D-glucuronic acid, D-glucaric acid, bovine submaxillary
mucin, heparin, and organic acids, such as citrate, 2-oxoglutaric acid, and D-2
hydroxyglutarate. Furthermore, HML27 had an affinity for alpha-D-galacturonic
acid, D-malate, L-malate, and pyruvate, while HML105 had an affinity for D
gluconic acid. HML27 and HML105 are novel plant lectins: they have an affinity
for sugar acids and organic acids and specifically recognize the carboxyl group,
and there is no homology between their N-terminal amino acid sequences and those
of the previously described lectins and agglutinins.
PMID- 27507268
TI - Schizophrenia and Infections: The Eyes Have It.
AB - The visual tract is prominently involved in schizophrenia, as evidenced by
perceptual distortions and a type of nystagmus found in many individuals
affected. Genetic explanations for these abnormalities have been suggested. This
study proposes an alternate explanation based on infection. Several infectious
agents thought to be associated with some cases of schizophrenia are known to
cause both infection of the fetus and abnormalities of the eye. Toxoplasma gondii
is examined in detail, and rubella, cytomegalovirus, varicella-zoster virus, and
herpes simplex virus more briefly. Careful ophthalmic assessments, including
funduscopy and direct examination of tissues for infectious agents, will clarify
the role of such agents in ocular aspects of schizophrenia.
PMID- 27507272
TI - Simultaneous Hydrogen and Methane Production Through Multi-Phase Anaerobic
Digestion of Paperboard Mill Wastewater Under Different Operating Conditions.
AB - Multi-phase anaerobic reactor for H2 and CH4 production from paperboard mill
wastewater was studied. The reactor was operated at hydraulic retention times
(HRTs) of 12, 18, 24, and 36 h, and organic loading rates (OLRs) of 2.2, 1.5,
1.1, and 0.75 kg chemical oxygen demand (COD)/m3 day, respectively. HRT of 12 h
and OLR of 2.2 kg COD/m3 day provided maximum hydrogen yield of 42.76 +/- 14.5
ml/g CODremoved and volumetric substrate uptake rate (-rS) of 16.51 +/- 4.43 mg
COD/L h. This corresponded to the highest soluble COD/total COD (SCOD/TCOD) ratio
of 56.25 +/- 3.3 % and the maximum volatile fatty acid (VFA) yield (YVFA) of 0.21
+/- 0.03 g VFA/g COD, confirming that H2 was mainly produced through SCOD
conversion. The highest methane yield (18.78 +/- 3.8 ml/g CODremoved) and -rS of
21.74 +/- 1.34 mgCOD/L h were achieved at an HRT of 36 h and OLR of 0.75 kg
COD/m3 day. The maximum hydrogen production rate (HPR) and methane production
rate (MPR) were achieved at carbon to nitrogen (C/N) ratio of 47.9 and 14.3,
respectively. This implies the important effect of C/N ratio on the distinction
between the dominant microorganism bioactivities responsible for H2 and CH4
production.
PMID- 27507279
TI - Development and validation of a climate-based ensemble prediction model for West
Nile Virus infection rates in Culex mosquitoes, Suffolk County, New York.
AB - BACKGROUND: West Nile Virus (WNV) is an endemic public health concern in the
United States that produces periodic seasonal epidemics. Underlying these
outbreaks is the enzootic cycle of WNV between mosquito vectors and bird hosts.
Identifying the key environmental conditions that facilitate and accelerate this
cycle can be used to inform effective vector control. RESULTS: Here, we model and
forecast WNV infection rates among mosquito vectors in Suffolk County, New York
using readily available meteorological and hydrological conditions. We first
validate a statistical model built with surveillance data between 2001 and 2009
(m09) and specify a set of new statistical models using surveillance data from
2001 to 2012 (m12). This ensemble of new models is then used to make predictions
for 2013-2015, and multimodel inference is employed to provide a formal
probabilistic interpretation across the disparate individual model predictions.
The findings of the m09 and m12 models align; with the ensemble of m12 models
indicating an association between warm, dry early spring (April) conditions and
increased annual WNV infection rates in Culex mosquitoes. CONCLUSIONS: This study
shows that real-time climate information can be used to predict WNV infection
rates in Culex mosquitoes prior to its seasonal peak and before WNV spillover
transmission risk to humans is greatest.
PMID- 27507281
TI - Reduction enthalpy and charge distribution of substituted ferrites and doped
ceria for thermochemical water and carbon dioxide splitting with DFT+U.
AB - The thermal reduction step of substituted ferrites (MFe2O4 where M = Fe, Ni, Co,
Gd) and doped ceria (MxCe1-xO2, where M = Ce, Zr, Hf and x = 0.25) in two-step
thermochemical cycles for H2O and CO2 splitting is investigated within the DFT+U
framework. This thermal reduction step is described as the oxygen vacancy
formation energy (reduction enthalpy), i.e. the energy required to create an
oxygen vacancy in the crystal lattice. Oxides with a lower oxygen vacancy
creation energy are easier to reduce. A Bader charge analysis of the reduction
mechanism is carried out providing the charge distribution of the bulk and
reduced ions, enabling interrelations of the substitute ions and the resulting
reduction energies. Based on the approach presented here, interesting solar fuels
producing materials are CoFe2O4, NiFe2O4 and Hf0.25Ce0.75O2.
PMID- 27507280
TI - Biomechanical Behavior of Bioprosthetic Heart Valve Heterograft Tissues:
Characterization, Simulation, and Performance.
AB - The use of replacement heart valves continues to grow due to the increased
prevalence of valvular heart disease resulting from an ageing population. Since
bioprosthetic heart valves (BHVs) continue to be the preferred replacement valve,
there continues to be a strong need to develop better and more reliable BHVs
through and improved the general understanding of BHV failure mechanisms. The
major technological hurdle for the lifespan of the BHV implant continues to be
the durability of the constituent leaflet biomaterials, which if improved can
lead to substantial clinical impact. In order to develop improved solutions for
BHV biomaterials, it is critical to have a better understanding of the inherent
biomechanical behaviors of the leaflet biomaterials, including chemical treatment
technologies, the impact of repetitive mechanical loading, and the inherent
failure modes. This review seeks to provide a comprehensive overview of these
issues, with a focus on developing insight on the mechanisms of BHV function and
failure. Additionally, this review provides a detailed summary of the
computational biomechanical simulations that have been used to inform and develop
a higher level of understanding of BHV tissues and their failure modes.
Collectively, this information should serve as a tool not only to infer reliable
and dependable prosthesis function, but also to instigate and facilitate the
design of future bioprosthetic valves and clinically impact cardiology.
PMID- 27507282
TI - Multimodal US-gamma imaging using collaborative robotics for cancer staging
biopsies.
AB - PURPOSE: The staging of female breast cancer requires detailed information about
the level of cancer spread through the lymphatic system. Common practice to
obtain this information for patients with early-stage cancer is sentinel lymph
node (SLN) biopsy, where LNs are radioactively identified for surgical removal
and subsequent histological analysis. Punch needle biopsy is a less invasive
approach but suffers from the lack of combined anatomical and nuclear
information. We present and evaluate a system that introduces live collaborative
robotic 2D gamma imaging in addition to live 2D ultrasound to identify SLNs in
the surrounding anatomy. METHODS: The system consists of a robotic arm equipped
with both a gamma camera and a stereoscopic tracking system that monitors the
position of an ultrasound probe operated by the physician. The arm cooperatively
places the gamma camera parallel to the ultrasound imaging plane to provide live
multimodal visualization and guidance. We validate the system by evaluating the
target registration errors between fused nuclear and US image data in a phantom
consisting of two spheres, one of which is filled with radioactivity. Medical
experts perform punch biopsies on agar-gelatine phantoms with complex
configurations of hot and cold lesions to provide a qualitative and quantitative
evaluation of the system. RESULTS: The average point registration error for the
overlay is [Formula: see text] mm. The time of the entire procedure was reduced
by 36 %, with 80v of the biopsies being successful. The users' feedback was very
positive, and the system was deemed to be very intuitive, with handling similar
to classic US-guided needle biopsy. CONCLUSION: We present and evaluate the first
medical collaborative robotic imaging system. Feedback from potential users for
SLN punch needle biopsy is encouraging. Ongoing work investigates the clinical
feasibility with more complex and realistic phantoms.
PMID- 27507285
TI - Reducing the width of confidence intervals for the difference between two
population means by inverting adaptive tests.
AB - In the last decade, it has been shown that an adaptive testing method could be
used, along with the Robbins-Monro search procedure, to obtain confidence
intervals that are often narrower than traditional confidence intervals. However,
these confidence interval limits require a great deal of computation and some
familiarity with stochastic search methods. We propose a method for estimating
the limits of confidence intervals that uses only a few tests of significance. We
compare these limits to those obtained by a lengthy Robbins-Monro stochastic
search and find that the proposed method is nearly as accurate as the Robbins
Monro search. Adaptive confidence intervals that are produced by the proposed
method are often narrower than traditional confidence intervals when the
distributions are long-tailed, skewed, or bimodal. Moreover, the proposed method
of estimating confidence interval limits is easy to understand, because it is
based solely on the p-values from a few tests of significance.
PMID- 27507283
TI - Ordered chromatin changes and human X chromosome reactivation by cell fusion
mediated pluripotent reprogramming.
AB - Erasure of epigenetic memory is required to convert somatic cells towards
pluripotency. Reactivation of the inactive X chromosome (Xi) has been used to
model epigenetic reprogramming in mouse, but human studies are hampered by Xi
epigenetic instability and difficulties in tracking partially reprogrammed iPSCs.
Here we use cell fusion to examine the earliest events in the reprogramming
induced Xi reactivation of human female fibroblasts. We show that a rapid and
widespread loss of Xi-associated H3K27me3 and XIST occurs in fused cells and
precedes the bi-allelic expression of selected Xi-genes by many heterokaryons (30
50%). After cell division, RNA-FISH and RNA-seq analyses confirm that Xi
reactivation remains partial and that induction of human pluripotency-specific
XACT transcripts is rare (1%). These data effectively separate pre- and post
mitotic events in reprogramming-induced Xi reactivation and reveal a complex
hierarchy of epigenetic changes that are required to reactivate the genes on the
human Xi chromosome.
PMID- 27507284
TI - Sexual orientation identity disparities in human papillomavirus vaccination
initiation and completion among young adult US women and men.
AB - PURPOSE: To examine the association between sexual orientation identity and human
papillomavirus (HPV) vaccination initiation and completion among both women and
men. METHODS: Using data from the 2013 and 2014 National Health Interview Survey,
we estimated logistic regression models for the association between sexual
orientation identity and HPV vaccination initiation (>=1 dose) and completion
(>=3 doses) among US women and men in relation to sociodemographic and healthcare
factors. Analyses were restricted to individuals for whom the HPV vaccine was
recommended at some point in their lives, namely women aged 18-34 years (n =
9,734) and men aged 18-31 years (n = 6,812). RESULTS: Among all women, bisexual
women had higher adjusted odds of HPV vaccination initiation [(odds ratio) 1.71;
(95 % confidence interval) 1.20-2.45] and completion (1.59; 1.05-2.42) than
heterosexual women. No difference was observed in the odds of HPV vaccination
initiation or completion between lesbian and heterosexual women. Among women who
had initiated HPV vaccination, lesbians had lower adjusted odds of completion
than heterosexual women (0.41; 0.19-0.90). Among all men, gay men had higher
adjusted odds of initiating (2.07; 1.17-3.52) and completing (3.90; 1.68-9.06)
HPV vaccination than heterosexual men. No difference was observed in the odds of
HPV vaccination initiation or completion between bisexual and heterosexual men.
Among men who had initiated HPV vaccination, gay (4.36; 1.28-14.83) and bisexual
(20.92; 2.34-186.73) men had higher adjusted odds of completion than heterosexual
men, although these results are unreliable and should be interpreted with
caution. CONCLUSIONS: Interventions are needed to promote HPV vaccination among
all US women and men, regardless of sexual orientation identity.
PMID- 27507286
TI - Sample size and classification error for Bayesian change-point models with
unlabelled sub-groups and incomplete follow-up.
AB - Many medical (and ecological) processes involve the change of shape, whereby one
trajectory changes into another trajectory at a specific time point. There has
been little investigation into the study design needed to investigate these
models. We consider the class of fixed effect change-point models with an
underlying shape comprised two joined linear segments, also known as broken-stick
models. We extend this model to include two sub-groups with different
trajectories at the change-point, a change and no change class, and also include
a missingness model to account for individuals with incomplete follow-up. Through
a simulation study, we consider the relationship of sample size to the estimates
of the underlying shape, the existence of a change-point, and the classification
error of sub-group labels. We use a Bayesian framework to account for the missing
labels, and the analysis of each simulation is performed using standard Markov
chain Monte Carlo techniques. Our simulation study is inspired by cognitive
decline as measured by the Mini-Mental State Examination, where our extended
model is appropriate due to the commonly observed mixture of individuals within
studies who do or do not exhibit accelerated decline. We find that even for
studies of modest size ( n = 500, with 50 individuals observed past the change
point) in the fixed effect setting, a change-point can be detected and reliably
estimated across a range of observation-errors.
PMID- 27507287
TI - Calibration of medical diagnostic classifier scores to the probability of
disease.
AB - Scores produced by statistical classifiers in many clinical decision support
systems and other medical diagnostic devices are generally on an arbitrary scale,
so the clinical meaning of these scores is unclear. Calibration of classifier
scores to a meaningful scale such as the probability of disease is potentially
useful when such scores are used by a physician. In this work, we investigated
three methods (parametric, semi-parametric, and non-parametric) for calibrating
classifier scores to the probability of disease scale and developed uncertainty
estimation techniques for these methods. We showed that classifier scores on
arbitrary scales can be calibrated to the probability of disease scale without
affecting their discrimination performance. With a finite dataset to train the
calibration function, it is important to accompany the probability estimate with
its confidence interval. Our simulations indicate that, when a dataset used for
finding the transformation for calibration is also used for estimating the
performance of calibration, the resubstitution bias exists for a performance
metric involving the truth states in evaluating the calibration performance.
However, the bias is small for the parametric and semi-parametric methods when
the sample size is moderate to large (>100 per class).
PMID- 27507288
TI - A multi-locus genetic association test for a dichotomous trait and its secondary
phenotype.
AB - Genetic association studies often collect information on secondary phenotypes
related to the primary disease status. In many situations, the secondary
phenotypes are only measured in subjects with the disease condition. It would be
advantageous to model the primary trait and the secondary phenotype together if
they share certain level of genetic heritability. We propose a family of multi
locus testing procedures to detect the composite association between a set of
genetic markers and two traits (the primary trait and a secondary phenotype), in
order to identify genes influencing both traits. The proposed test is derived
from a random effect model with two variance components, with each presenting the
genetic effect on one trait, and incorporates a model selection procedure for
seeking the optimal model to represent the two sources of genetic effects. We
conduct simulation studies to evaluate performance of the proposed procedure and
apply the method to a genome-wide association study of prostate cancer with the
Gleason score as the secondary phenotype.
PMID- 27507289
TI - A new parsimonious model for ordinal longitudinal data with application to
subjective evaluations of a gastrointestinal disease.
AB - In this paper, a new discrete statistical model for ordered categorical data is
proposed via fixed-point discretization of a beta latent variable. The resulting
discretized beta distribution has a highly flexible shape and it can be either
over-dispersed or under-dispersed with respect to the binomial distribution. It
has only two parameters, which may therefore parsimoniously depend on covariates
and on random effects, providing new tools for the analysis of structured,
clustered or longitudinal ordinal data. Practical examples and advices are given
and an application of the new model to subjective evaluations of a
gastrointestinal disease is shown.
PMID- 27507290
TI - Efficient Monte Carlo evaluation of resampling-based hypothesis tests with
applications to genetic epidemiology.
AB - Monte Carlo evaluation of resampling-based tests is often conducted in
statistical analysis. However, this procedure is generally computationally
intensive. The pooling resampling-based method has been developed to reduce the
computational burden but the validity of the method has not been studied before.
In this article, we first investigate the asymptotic properties of the pooling
resampling-based method and then propose a novel Monte Carlo evaluation procedure
namely the n-times pooling resampling-based method. Theorems as well as
simulations show that the proposed method can give smaller or comparable root
mean squared errors and bias with much less computing time, thus can be strongly
recommended especially for evaluating highly computationally intensive hypothesis
testing procedures in genetic epidemiology.
PMID- 27507291
TI - Successful completion of a semi-automated enzyme-free cloning method.
AB - Nowadays, in scientific fields such as Structural Biology or Vaccinology, there
is an increasing need of fast, effective and reproducible gene cloning and
expression processes. Consequently, the implementation of robotic platforms
enabling the automation of protocols is becoming a pressing demand. The main goal
of our study was to set up a robotic platform devoted to the high-throughput
automation of the polymerase incomplete primer extension cloning method, and to
evaluate its efficiency compared to that achieved manually, by selecting a set of
bacterial genes that were processed either in the automated platform (330) or
manually (94). Here we show that we successfully set up a platform able to
complete, with high efficiency, a wide range of molecular biology and biochemical
steps. 329 gene targets (99 %) were effectively amplified using the automated
procedure and 286 (87 %) of these PCR products were successfully cloned in
expression vectors, with cloning success rates being higher for the automated
protocols respect to the manual procedure (93.6 and 74.5 %, respectively).
PMID- 27507293
TI - Materials in the vitreous during standard cataract surgery: concept not verified
yet.
PMID- 27507292
TI - The economic burden of urinary tract infections in women visiting general
practices in France: a cross-sectional survey.
AB - BACKGROUND: Urinary tract infections (UTIs) are among the most common bacterial
infections. Despite this burden, there are few studies of the costs of UTIs. The
objective of this study was to determine the costs of UTIs in women over 18 years
of age who visit general practitioners in France. METHODS: The direct and
indirect costs of clinical UTIs were estimated from societal, French National
Health Insurance and patient perspectives. The study population was derived from
a national cross-sectional survey entitled the Drug-Resistant Urinary Tract
Infection (Druti). The Druti included every woman over 18 years of age who
presented with symptoms of UTI and was conducted in France in 2012 and 2013 to
estimate the annual incidence of UTIs due to antibiotic-resistant
Enterobacteriaceae in women visiting general practitioners (GPs) for suspected
UTIs. RESULTS: Of the 538 women included in Druti, 460 were followed over 8 weeks
and included in the cost analysis. The mean age of the women was 46 years old.
The median cost of care for one episode of a suspected UTI was ?38, and the mean
cost was ?70. The annual societal cost was ?58 million, and ?29 million of this
was reimbursed by the French National Health Insurance system. In 25 % of the
cases, the suspected UTIs were associated with negative urine cultures. The
societal cost of these suspected UTIs with negative urine cultures was ?13.5
million. No significant difference was found between the costs of the UTIs due to
antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63).
CONCLUSION: In the current context in which the care costs are continually
increasing, the results of this study suggests that it is possible to decrease
the cost of UTIs by reducing the costs of suspected UTIs and unnecessary
treatments, as well as limiting the use of non-recommended tests.
PMID- 27507295
TI - Reusable sanitary towels: promoting menstrual hygiene in post-earthquake Nepal.
AB - It is a normal human tendency to 'run for your life' when an earthquake occurs.
Adolescent girls and women of reproductive age leave their homes with only the
clothes they are wearing to save their own and their families' lives. Immediate
disaster relief aid with its (unintentional) lack of gender sensitivity has
little or no materials for the appropriate management of menstrual hygiene. The
biological needs of disaster-affected women will not change despite the dire need
for basic food, shelter and security. Timely identification and preparation
beforehand with appropriate and culturally sensitive techniques and locally
available materials that are reusable can help introduce sustainable and
acceptable means of managing menstrual hygiene in a crisis. The use of reusable
sanitary towels is well accepted for menstrual hygiene management in non-disaster
situations and is appropriate in post-earthquake relief in Nepal.
PMID- 27507296
TI - Brain atlas of the Mongolian gerbil (Meriones unguiculatus) in CT/MRI-aided
stereotaxic coordinates.
AB - A new stereotaxic brain atlas of the Mongolian gerbil (Meriones unguiculatus), an
important animal model in neurosciences, is presented. It combines high-quality
histological material for identification of brain structures with reliable
stereotaxic coordinates. The atlas consists of high-resolution images of frontal
sections alternately stained for cell bodies (Nissl) and myelinated fibers
(Gallyas) of 62 rostro-caudal levels at intervals of 350 MUm. Brain structures
were named according to the Paxinos nomenclature for rodents. The accuracy of the
stereotaxic coordinate system was improved substantially by comparing and
matching the series of histological sections to in vivo brain images of the
gerbil obtained by magnetic resonance imaging (MRI). The skull outlines
corresponding to the MR images were acquired using X-ray computerized tomography
(CT) and were used to establish the relationship between coordinates of brain
structures and skull. Landmarks such as lambda, bregma, ear canals and occipital
crest can be used to line up skull and brain in standard atlas coordinates. An
easily reproducible protocol allows sectioning of experimental brains in the
standard frontal plane of the atlas.
PMID- 27507297
TI - Investigation of avian haemosporidian parasites from raptor birds in Turkey, with
molecular characterisation and microscopic confirmation.
AB - Avian haemosporidians are common vector-borne blood parasites that have been
reported in birds all over the world. Investigations of avian haemosporidian
parasites are conducted mainly on passerine birds. However, studies that focus on
non-passerine avian hosts are important for our understanding of the true
diversity, host specificity and genetic variability among these widespread
parasites. In the present study, blood samples from a total of 22 raptor birds
belonging to two orders, two families and six species from the Central Anatolia
Region of Turkey were investigated for three genera of avian haemosporidians
(Plasmodium Marchiafava et Celli, 1885, Haemoproteus Kruse, 1890 and
Leucocytozoon Sambon, 1908) using a combination of microscopic examination of
blood films and nested PCR targeting the parasite mitochondrial cytochrome b gene
(cyt-b). In total, six individual raptor birds identified positive for species of
Plasmodium or Leucocytozoon and one individual was found co-infected with all
three haemosporidian genera. We identified five parasite cyt-b haplotypes, three
of which were reported for the first time. Among these, one Plasmodium haplotype
is linked to a corresponding morphospecies (P-TURDUS1, Plasmodium circumflexum
Kikuth, 1931). All haplotypes were clearly distinguishable in phylogenetic
analyses. As one of the first studies to investigate blood parasites from non
passerine birds in the Central Anatolia Region of Turkey, this study provides
important new information on the phylogenetic relationships and genetic diversity
of avian haemosporidian parasites from raptor birds. We discuss these findings in
the context of avian haemosporidian host-parasite relationships and we draw
attention to the need for microscopy to detect parasite sexual development stages
in surveys of avian haemosporidians.
PMID- 27507298
TI - Estimation of the need for bilateral intravitreal anti-VEGF injections in
clinical practice.
AB - BACKGROUND: To estimate the need for bilateral intravitreal anti-VEGF injections
in patients treated for neovascular age-related macular degeneration (nAMD),
diabetic macular edema (DME), retinal vein occlusion, choroidal
neovascularization (CNV) in high myopia, and other causes of CNV. METHODS: All
consecutive patients treated with intravitreal anti-VEGF injection over a 1-month
period were included in a prospective multicenter survey. The reason for
intravitreal anti-VEGF injection and the involvement of the fellow eye in the
pathology requiring a treatment with intravitreal anti-VEGF were recorded. A time
interval between bilateral injections longer than 1 month, within a 1-month
period, and same-day bilateral injections were recorded. RESULTS: A total of 1335
patients were included, corresponding to 1024 (76.7 %) patients treated for nAMD,
167 (12.5 %) for DME, and 144 (10.8 %) for other reasons. Four hundred and fifty
nine (34.4 %) patients were treated bilaterally with a time interval between
injections longer than 1 month, 170 (12.7 %) were treated bilaterally within a 1
month interval, and 87 (6.6 %) had same-day bilateral injections. Bilateral
injections were more frequent in diabetic patients than in nAMD patients
(respectively 48 % vs. 36 %, p = 0.0033). CONCLUSIONS: Patients with DME are more
likely to be treated bilaterally with anti-VEGF injections. As the rate of second
eye involvement requiring treatment increases progressively over time, a same-day
bilateral injection strategy will become more common as it decreases the
administrative burden on the healthcare system and treatment burden experienced
by patients.
PMID- 27507299
TI - Impact of chemotherapy on the outcome of osteosarcoma of the head and neck in
adults.
AB - BACKGROUND: There is an ongoing debate about the value of (neo-)adjuvant
chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck.
METHODS: All records of patients older than 16 years diagnosed with osteosarcoma
of the head and neck in the Netherlands between 1993 and 2013 were reviewed.
RESULTS: We identified a total of 77 patients with an osteosarcoma of the head
and neck; the 5-year overall survival (OS) was 55%. In 50 patients with
surgically resected high- or intermediate-grade osteosarcoma of the head and neck
younger than 75 years, univariate and multivariable analysis, adjusting for age
and resection margins, showed that patients who had not received chemotherapy had
a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and
3.66, respectively). CONCLUSION: In patients younger than 75 years of age with
surgically resected high- and intermediate-grade osteosarcoma of the head and
neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly
smaller risk of local recurrence. Therefore, we suggest (neo-)adjuvant
chemotherapy in patients amenable to chemotherapy. (c) 2016 The Authors Head &
Neck Published by Wiley Periodicals, Inc. Head Neck 39: 140-146, 2017.
PMID- 27507300
TI - An approach to measuring and encouraging research translation and research
impact.
AB - BACKGROUND: Research translation, particularly in the biomedical area, is often
discussed but there are few methods that are routinely used to measure it or its
impact. Of the impact measurement methods that are used, most aim to provide
accountability - to measure and explain what was generated as a consequence of
funding research. This case study reports on the development of a novel,
conceptual framework that goes beyond measurement. The Framework To Assess the
Impact from Translational health research, or FAIT, is a platform designed to
prospectively measure and encourage research translation and research impact. A
key assumption underpinning FAIT is that research translation is a prerequisite
for research impact. METHODS: The research impact literature was mined to
understand the range of existing frameworks and techniques employed to measure
and encourage research translation and research impact. This review provided
insights for the development of a FAIT prototype. A Steering Committee oversaw
the project and provided the feedback that was used to refine FAIT. RESULTS: The
outcome of the case study was the conceptual framework, FAIT, which is based on a
modified program logic model and a hybrid of three proven methodologies for
measuring research impact, namely a modified Payback method, social return on
investment, and case studies or narratives of the process by which research
translates and generates impact. CONCLUSION: As funders increasingly seek to
understand the return on their research investments, the routine measurement of
research translation and research impact is likely to become mandatory rather
than optional. Measurement of research impact on its own is insufficient. There
should also be a mechanism attached to measurement that encourages research
translation and impact - FAIT was designed for this task.
PMID- 27507301
TI - MicroRNA 101b Is Downregulated in the Prefrontal Cortex of a Genetic Model of
Depression and Targets the Glutamate Transporter SLC1A1 (EAAT3) in Vitro.
AB - BACKGROUND: MicroRNAs (miRNAs) are small regulatory molecules that cause
translational repression by base pairing with target mRNAs. Cumulative evidence
suggests that changes in miRNA expression may in part underlie the
pathophysiology and treatment of neuropsychiatric disorders, including major
depressive disorder (MDD). METHODS: A miRNA expression assay that can
simultaneously detect 423 rat miRNAs (miRBase v.17) was used to profile the
prefrontal cortex (PFC) of a genetic rat model of MDD (the Flinders Sensitive
Line [FSL]) and the controls, the Flinders Resistant Line (FRL). Gene expression
data from the PFC of FSL/FRL animals (GEO accession no. GSE20388) were used to
guide mRNA target selection. Luciferase reporter assays were used to verify miRNA
targets in vitro. RESULTS: We identified 23 miRNAs that were downregulated in the
PFC of the FSL model compared with controls. Interestingly, one of the identified
miRNAs (miR-101b) is highly conserved between rat and human and was recently
found to be downregulated in the PFC of depressed suicide subjects. Using a
combination of in silico and in vitro analyses, we found that miR-101b targets
the neuronal glutamate transporter SLC1A1 (also known as EAAC1 or EAAT3).
Accordingly, both mRNA and protein levels of SLC1A1 were found to be upregulated
in the PFC of the FSL model. CONCLUSIONS: Besides providing a list of novel
miRNAs associated with depression-like states, this preclinical study replicated
the human association of miR-101 with depression. In addition, since one of the
targets of miR-101b appears to be a glutamate transporter, our preclinical data
support the hypothesis of a glutamatergic dysregulation being implicated in the
etiology of depression.
PMID- 27507302
TI - Clinical Interpretation of Genomic Variations.
AB - Novel high-throughput sequencing technologies generate large-scale genomic data
and are used extensively for disease mapping of monogenic and/or complex
disorders, personalized treatment, and pharmacogenomics. Next-generation
sequencing is rapidly becoming routine tool for diagnosis and molecular
monitoring of patients to evaluate therapeutic efficiency. The next-generation
sequencing platforms generate huge amounts of genetic variation data and it
remains a challenge to interpret the variations that are identified. Such data
interpretation needs close collaboration among bioinformaticians, clinicians, and
geneticists. There are several problems that must be addressed, such as the
generation of new algorithms for mapping and annotation, harmonization of the
terminology, correct use of nomenclature, reference genomes for different
populations, rare disease variant databases, and clinical reports.
PMID- 27507303
TI - Benefits of interventions for respiratory secretion management in adult
palliative care patients-a systematic review.
AB - BACKGROUND: Respiratory secretions impact negatively on palliative patients.
Unfortunately, a gold standard therapy is not yet available. The purpose of this
study was to identify which interventions are in use to control respiratory
secretions in patients with chronic disease with a poor prognosis and verify
their effects on outcomes relevant for palliative care patients. METHODS: A
systematic review of the literature with narrative summary was conducted. We
searched eight electronic databases in April (6th), 2016. Citation-tracking and
reference list searches were conducted. We included randomized controlled trials,
crossover trials, observational and qualitative studies regarding interventions
for respiratory secretion management in adult patients with chronic diseases that
met inclusion criteria indicating short prognosis. RESULTS: Six randomized
controlled trials, 11 observational studies, ten crossover trials and one
qualitative study were found. Interventions included mechanical insufflation
exsufflation (MIE), expiratory muscle training, manually-assisted cough,
tracheotomy, chest physiotherapy, suctioning, air stacking, electrical
stimulation of abdominal muscles, nebulized saline, positive expiratory pressure
masks, percussive ventilation, high frequency chest wall oscillations. The
interventions with most promising benefits to patients in palliative care were
manually-assisted cough and mechanical insufflation-exsufflation to promote
expectoration and percussive ventilation to improve mucous clearance. CONCLUSION:
Therapies, such as manually assisted cough, mechanical insufflation-exsufflation
and percussive ventilation, which aim to deal with respiratory secretion, were
the most promising treatment for use in palliative care for specific diseases.
Nevertheless, the evidence still needs to improve in order to identify which
treatment is the best.
PMID- 27507304
TI - Compression of the superior mesenteric vein-a sign of acute internal herniation
in patients with antecolic laparoscopic Roux-en-Y gastric bypass.
AB - OBJECTIVES: To investigate whether compression of the superior mesenteric vein
(SMV) on computed tomography (CT) can serve as a valid sign of internal
herniation (IH) in patients with antecolic laparoscopic Roux-en-Y gastric bypass
(LRYGBP). MATERIALS AND METHODS: With institutional review board approval, we
performed a retrospective analysis of 41 patients with antecolic LRYGBP referred
for acute CT of the abdomen with suspicion of IH or another cause of acute
abdomen. CT scans were randomly reviewed for signs of IH by two radiologists in a
blinded manner, and the findings were correlated with the results of the
patients' bariatric workup. Sensitivity, specificity, and inter-observer
agreement were calculated for each sign. RESULTS: Five patients were classified
as having intermittent IH and were excluded. Eighteen patients were found to have
IH at laparoscopy and served as the study group; 18 patients served as the
control group. SMV compression had the best sensitivity (67 % for both reviewers)
and inter-observer agreement (kappa = 0.82) of all investigated signs. The swirl
sign showed a lower sensitivity (39 and 50 % respectively) and kappa (0.37).
CONCLUSION: SMV compression is a reliable sign of IH in patients with antecolic
LRYGBP. KEY POINTS: * CT can help detect internal herniation after laparoscopic
Roux-en-Y gastric bypass. * Compression of the superior mesenteric vein is a sign
of internal herniation. * This sign has a high inter-observer-agreement. * A
diagnosis of internal herniation can be made with greater confidence.
PMID- 27507305
TI - Analysis of thulium fiber laser induced bubble dynamics for ablation of kidney
stones.
AB - The Thulium fiber laser (TFL) is being explored as an alternative to the Holmium
: YAG laser for lithotripsy. TFL parameters differ in several fundamental ways
from Holmium laser, including smaller fiber delivery, more strongly absorbed
wavelength, low pulse energy/high pulse rate operation, and more uniform temporal
pulse structure. High speed imaging of laser induced bubbles was performed at
105,000 frames per second and 10 MUm spatial resolution to determine influence of
these laser parameters on bubble formation and needle hydrophone data was also
used to measure pressure transients. The TFL was operated at 1908 nm with pulse
energies of 5-65 mJ, and pulse durations of 200-1000 MUs, delivered through 105
MUm-core and 270-MUm-core silica optical fibers. Bubble dynamics using Holmium
laser at a wavelength of 2100 nm with pulse energies of 200-1000 mJ and pulse
duration of 350 MUs was studied, for comparison. A single, 500 MUs TFL pulse
produced a bubble stream extending 1200 +/- 90 MUm and 1070 +/- 50 MUm from fiber
tip, with maximum bubble widths averaging 650 +/- 20 MUm and 870 +/- 40 MUm (n =
4), for 105 MUm and 270 MUm fibers, respectively. These observations are
consistent with previous studies which reported TFL ablation stallout at working
distances beyond 1.0 mm. TFL bubble dimensions were four times smaller than for
Holmium laser due to lower peak power and smaller fiber diameter used. The
maximum pressure transients measured 0.6 bars at 35 mJ pulse energy for TFL and
7.5 bars at 600 mJ pulse energy for Holmium laser. These fundamental studies of
bubble dynamics as a function of specific laser and fiber parameters may assist
with optimization of the TFL parameters for safe and efficient lithotripsy in the
clinic. Image of bubble formation during fiber optic delivery of Thulium fiber
laser energy in saline (35 mJ, 500 MUs).
PMID- 27507306
TI - Is it better to overtreat or undertreat?
PMID- 27507307
TI - Do we end life well?
PMID- 27507308
TI - Iron deficiency anemia: like mother, like child.
PMID- 27507309
TI - Nonsteroidal anti-inflammatory drugs: risks outweigh benefits.
PMID- 27507310
TI - A severity score in PGM-1 deficiency.
PMID- 27507312
TI - Blunted response: smoke, illicit substances, and how babies breathe.
PMID- 27507311
TI - Hypothermia at NICU admission in very preterm infants.
PMID- 27507313
TI - 50 Years Ago in TheJournal ofPediatrics: Legislation and Advances in Medical
Knowledge-Acceleration or Inhibition?
PMID- 27507314
TI - 50 Years Ago in TheJournal ofPediatrics: Nutritional and Antigenic Effects of 2
Bovine Milk Preparations in Infants.
PMID- 27507315
TI - 50 Years Ago in TheJournal ofPediatrics: The Sweat Test in Cystic Fibrosis: A
Comparison of Overnight Sweat Collection versus the Pilocarpine Iontophoresis
Method.
PMID- 27507317
TI - Correction.
PMID- 27507316
TI - 50 Years Ago in TheJournal ofPediatrics: An Outbreak of Coxsackie B-5 Virus
Infection in a Newborn Nursery.
PMID- 27507318
TI - Correction.
PMID- 27507319
TI - Vaccine Hesitancy and Refusal.
PMID- 27507320
TI - The SAGES telephone neuropsychological battery: correlation with in-person
measures.
AB - OBJECTIVE: Neuropsychological test batteries are administered in person to assess
cognitive function in both clinical and research settings. However, in-person
administration holds a number of logistical challenges that makes it difficult to
use in large or remote populations or for multiple serial assessments over time.
The purpose of this descriptive study was to determine whether a telephone
administered neuropsychological test battery correlated well with in-person
testing. METHODS: Fifty English-speaking patients without dementia, over 70 years
old, and part of a cohort of patients in a prospective cohort study examining
cognitive outcomes following elective surgery were enrolled in this study. Five
well-validated neuropsychological tests were administered by telephone to each
participant by a trained interviewer within 2-4 weeks of the most recent in
person interview. Tests included the Hopkins Verbal Learning Test-Revised, Digit
Span, Category Fluency, Phonemic Fluency, and Boston Naming Test. A General
Cognitive Performance composite score was calculated from individual subtest
scores as a Z-score. RESULTS: Mean age was 74.9 years (SD = 4.1), 66% female, and
4% non-White. Mean and interquartile distributions of telephone scores were
similar to in-person scores. Correlation analysis of test scores revealed
significant correlations between telephone and in-person results for each
individual subtest, as well as for the overall composite score. A Bland-Altman
plot revealed no bias or trends in scoring for either test administration type.
CONCLUSIONS: In this descriptive study, the telephone version of a
neuropsychological test battery correlated well with the in-person version and
may provide a feasible supplement in clinical and research applications.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27507321
TI - Global synthesis suggests that food web connectance correlates to invasion
resistance.
AB - Biological invasions are a key component of global change, and understanding the
drivers of global invasion patterns will aid in assessing and mitigating the
impact of invasive species. While invasive species are most often studied in the
context of one or two trophic levels, in reality species invade communities
comprised of complex food webs. The complexity and integrity of the native food
web may be a more important determinant of invasion success than the strength of
interactions between a small subset of species within a larger food web. Previous
efforts to understand the relationship between food web properties and species
invasions have been primarily theoretical and have yielded mixed results. Here,
we present a synthesis of empirical information on food web connectance and
species invasion success gathered from different sources (estimates of food web
connectance from the primary literature and estimates of invasion success from
the Global Invasive Species Database as well as the primary literature). Our
results suggest that higher-connectance food webs tend to host fewer invaders and
exert stronger biotic resistance compared to low-connectance webs. We argue that
while these correlations cannot be used to infer a causal link between food web
connectance and habitat invasibility, the promising findings beg for further
empirical research that deliberately tests for relationships between food web
connectance and invasion.
PMID- 27507322
TI - A fully automated microfluidic micellar electrokinetic chromatography analyzer
for organic compound detection.
AB - An integrated microfluidic chemical analyzer utilizing micellar electrokinetic
chromatography (MEKC) is developed using a pneumatically actuated Lifting-Gate
microvalve array and a capillary zone electrophoresis (CZE) chip. Each of the
necessary liquid handling processes such as metering, mixing, transferring, and
washing steps are performed autonomously by the microvalve array. In addition, a
method is presented for automated washing of the high resistance CZE channel for
device reuse and periodic automated in situ analyses. To demonstrate the
functionality of this MEKC platform, amino acids and thiols are labeled and
efficiently separated via a fully automated program. Reproducibility of the
automated programs for sample labeling and periodic in situ MEKC analysis was
tested and found to be equivalent to conventional sample processing techniques
for capillary electrophoresis analysis. This platform enables simple, portable,
and automated chemical compound analysis which can be used in challenging
environments.
PMID- 27507323
TI - Immunological characterization of de novo and recall alloantibody suppression by
CTLA4Ig in a mouse model of allosensitization.
AB - It is well known that CTLA4Ig inhibits allogenic T-cell activation in
transplantation. The immunological features and mechanisms associated with
alloantibody suppression by CTLA4Ig, however, are poorly understood. Here, we
used a mouse model of allosensitization to evaluate the efficacy of CTLA4Ig
(abatacept) in suppression of donor-specific antibody (DSA) during de novo and
recall alloantibody responses. We found that abatacept inhibited de novo DSA IgM
and IgG responses to HLA-A2 expressing skin grafts. Abatacept administered during
primary T cell priming also reduced recall IgG responses induced by re
immunization. Suppression of de novo DSA responses by abatacept is associated
with a reduction in splenic expression of the germinal center activation marker
GL7 and a reduction of CD4(+)PD1(+)CXCR5(+) follicular T helper (Tfh) subset in
splenic lymphocytes detected by flow cytometry. The efficacy of abatacept on
recall DSA suppression is moderate. In vitro experiments demonstrated that
abatacept inhibited DSA IgG secretion by CD138(+) plasma cells isolated from
allograft recipients. Additional experiments using an IgG1 secreting mouse
hybridoma cell line showed that abatacept binds to CD80 expressed on these cells
with subsequent inhibition of cell proliferation and reduction in IgG ELISpot
formation. In conclusion, CTLA4Ig is a potent suppressor of de novo DSA responses
and also affects recall responses. The data suggests modification of recall DSA
responses is due to a direct suppressive effect on plasma cells.
PMID- 27507324
TI - Ensemble based adaptive over-sampling method for imbalanced data learning in
computer aided detection of microaneurysm.
AB - Diabetic retinopathy (DR) is a progressive disease, and its detection at an early
stage is crucial for saving a patient's vision. An automated screening system for
DR can help in reduce the chances of complete blindness due to DR along with
lowering the work load on ophthalmologists. Among the earliest signs of DR are
microaneurysms (MAs). However, current schemes for MA detection appear to report
many false positives because detection algorithms have high sensitivity.
Inevitably some non-MAs structures are labeled as MAs in the initial MAs
identification step. This is a typical "class imbalance problem". Class
imbalanced data has detrimental effects on the performance of conventional
classifiers. In this work, we propose an ensemble based adaptive over-sampling
algorithm for overcoming the class imbalance problem in the false positive
reduction, and we use Boosting, Bagging, Random subspace as the ensemble
framework to improve microaneurysm detection. The ensemble based over-sampling
methods we proposed combine the strength of adaptive over-sampling and ensemble.
The objective of the amalgamation of ensemble and adaptive over-sampling is to
reduce the induction biases introduced from imbalanced data and to enhance the
generalization classification performance of extreme learning machines (ELM).
Experimental results show that our ASOBoost method has higher area under the ROC
curve (AUC) and G-mean values than many existing class imbalance learning
methods.
PMID- 27507325
TI - Incorporation of gradient vector flow field in a multimodal graph-theoretic
approach for segmenting the internal limiting membrane from glaucomatous optic
nerve head-centered SD-OCT volumes.
AB - The internal limiting membrane (ILM) separates the retina and optic nerve head
(ONH) from the vitreous. In the optical coherence tomography volumes of glaucoma
patients, while current approaches for the segmentation of the ILM in the
peripapillary and macular regions are considered robust, current approaches
commonly produce ILM segmentation errors at the ONH due to the presence of blood
vessels and/or characteristic glaucomatous deep cupping. Because a precise
segmentation of the ILM surface at the ONH is required for computing several
newer structural measurements including Bruch's membrane opening-minimum rim
width (BMO-MRW) and cup volume, in this study, we propose a multimodal
multiresolution graph-based method to precisely segment the ILM surface within
ONH-centered spectral-domain optical coherence tomography (SD-OCT) volumes. In
particular, the gradient vector flow (GVF) field, which is computed from a
multiresolution initial segmentation, is employed for calculating a set of non
overlapping GVF-based columns perpendicular to the initial segmentation. The GVF
columns are utilized to resample the volume and also serve as the columns to the
graph construction. The ILM surface in the resampled volume is fairly smooth and
does not contain the steep slopes. This prior shape knowledge along with the
blood vessel information, obtained from registered fundus photographs, are
incorporated in a graph-theoretic approach in order to identify the location of
the ILM surface. The proposed method is tested on the SD-OCT volumes of 44
subjects with various stages of glaucoma and significantly smaller segmentation
errors were obtained than that of current approaches.
PMID- 27507326
TI - Volumetric image classification using homogeneous decomposition and dictionary
learning: A study using retinal optical coherence tomography for detecting age
related macular degeneration.
AB - Three-dimensional (3D) (volumetric) diagnostic imaging techniques are
indispensable with respect to the diagnosis and management of many medical
conditions. However there is a lack of automated diagnosis techniques to
facilitate such 3D image analysis (although some support tools do exist). This
paper proposes a novel framework for volumetric medical image classification
founded on homogeneous decomposition and dictionary learning. In the proposed
framework each image (volume) is recursively decomposed until homogeneous regions
are arrived at. Each region is represented using a Histogram of Oriented
Gradients (HOG) which is transformed into a set of feature vectors. The Gaussian
Mixture Model (GMM) is then used to generate a "dictionary" and the Improved
Fisher Kernel (IFK) approach is used to encode feature vectors so as to generate
a single feature vector for each volume, which can then be fed into a classifier
generator. The principal advantage offered by the framework is that it does not
require the detection (segmentation) of specific objects within the input data.
The nature of the framework is fully described. A wide range of experiments was
conducted with which to analyse the operation of the proposed framework and these
are also reported fully in the paper. Although the proposed approach is generally
applicable to 3D volumetric images, the focus for the work is 3D retinal Optical
Coherence Tomography (OCT) images in the context of the diagnosis of Age-related
Macular Degeneration (AMD). The results indicate that excellent diagnostic
predictions can be produced using the proposed framework.
PMID- 27507327
TI - Salvianolic acid B protects against paraquat-induced pulmonary injury by
mediating Nrf2/Nox4 redox balance and TGF-beta1/Smad3 signaling.
AB - The present study was aimed at exploring the protective effects of Salvianolic
acid B (SalB) against paraquat (PQ)-induced lung injury in mice. Lung fibrotic
injuries were induced in mice by a single intragastrical administration of
300mg/kg PQ, then the mice were administrated with 200mg/kg, 400mg/kg SalB,
100mg/kg vitamin C (Vit C) and dexamethasone (DXM) for 14days. PQ-triggered
structure distortion, collagen overproduction, excessive inflammatory
infiltration, pro-inflammatory cytokine release, and oxidative stress damages in
lung tissues and mortality of mice were attenuated by SalB in a dose-dependent
manner. Furthermore, SalB was noted to enhance the expression and nuclear
translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduce
expression of the reactive oxygen species-generating enzyme Nox4 [NADPH (reduced
form of nicotinamide adenine dinucleotide phosphate) oxidase-4]. SalB also
inhibited the increasing expression of transforming growth factor (TGF)-beta1 and
the phosphorylation of its downstream target Smad3 which were enhanced by PQ.
These results suggest that SalB may exert protective effects against PQ-induced
lung injury and pulmonary fibrosis. Its mechanisms involve the mediation of
Nrf2/Nox4 redox balance and TGF-beta1/Smad3 signaling.
PMID- 27507329
TI - Restriction Endonuclease Analysis Typing of Clostridium difficile Isolates.
AB - Restriction endonuclease analysis (REA) typing using HindIII enzyme is a highly
discriminatory, reproducible, and consistent method of genetic typing of
Clostridium difficile (CD) isolates. REA typing analyzes CD whole cellular DNA on
two levels of discrimination: REA Group designation and REA Type designation,
which distinguishes specific subtypes within the REA Group. This methodology has
enabled the tracking of epidemiologically significant CD strains over time and in
some cases has allowed documentation of the evolution of previously rare REA
Group strains that have subsequently become epidemic. The chapter details the
methods used to isolate and purify CD colonies from stool samples, to obtain
intact, full-length whole cellular DNA from CD isolates by use of guanidine-EDTA
solution, and to analyze the HindIII-digested DNA after electrophoretic
separation on agarose gels.
PMID- 27507328
TI - Environmental variables and definitive host distribution: a habitat suitability
modelling for endohelminth parasites in the marine realm.
AB - Marine nematodes of the genus Anisakis are common parasites of a wide range of
aquatic organisms. Public interest is primarily based on their importance as
zoonotic agents of the human Anisakiasis, a severe infection of the gastro
intestinal tract as result of consuming live larvae in insufficiently cooked fish
dishes. The diverse nature of external impacts unequally influencing larval and
adult stages of marine endohelminth parasites requires the consideration of both
abiotic and biotic factors. Whereas abiotic factors are generally more relevant
for early life stages and might also be linked to intermediate hosts, definitive
hosts are indispensable for a parasite's reproduction. In order to better
understand the uneven occurrence of parasites in fish species, we here use the
maximum entropy approach (Maxent) to model the habitat suitability for nine
Anisakis species accounting for abiotic parameters as well as biotic data
(definitive hosts). The modelled habitat suitability reflects the observed
distribution quite well for all Anisakis species, however, in some cases, habitat
suitability exceeded the known geographical distribution, suggesting a wider
distribution than presently recorded. We suggest that integrative modelling
combining abiotic and biotic parameters is a valid approach for habitat
suitability assessments of Anisakis, and potentially other marine parasite
species.
PMID- 27507330
TI - Direct PCR-Ribotyping of Clostridium difficile.
AB - PCR-ribotyping, a method based on heterogeneity of ribosomal intergenic spacer
region, is the preferred method for genotyping of Clostridium difficile.
Standardly used procedure for PCR-ribotyping is culturing of C. difficile from
fecal samples and subsequent typing. In this chapter, we describe a modified PCR
ribotyping method for direct detection of PCR-ribotypes directly in total stool
DNA extract, without prior need to isolate C. difficile.
PMID- 27507331
TI - From FASTQ to Function: In Silico Methods for Processing Next-Generation
Sequencing Data.
AB - This chapter presents a method to process C. difficile whole-genome next
generation sequencing data straight from the sequencer. Quality control
processing and de novo assembly of these data enable downstream analyses such as
gene annotation and in silico multi-locus strain-type identification.
PMID- 27507332
TI - Clostridium difficile Genome Editing Using pyrE Alleles.
AB - Precise manipulation (in-frame deletions and substitutions) of the Clostridium
difficile genome is possible through a two-stage process of single-crossover
integration and subsequent isolation of double-crossover excision events using
replication-defective plasmids that carry a counterselection marker. Use of a
codA (cytosine deaminase) or pyrE (orotate phosphoribosyltransferase) as counter
selection markers appears equally effective, but there is considerable merit in
using a pyrE mutant as the host as, through the use of allele-coupled exchange
(ACE) vectors, mutants created (by whatever means) can be rapidly complemented
concomitant with restoration of the pyrE allele. This avoids the phenotypic
effects frequently observed with high-copy-number plasmids and dispenses with the
need to add antibiotic to ensure plasmid retention.
PMID- 27507333
TI - Use of mCherryOpt Fluorescent Protein in Clostridium difficile.
AB - Here we describe protocols for using the red fluorescent protein mCherryOpt in
Clostridium difficile. The protocols can be readily adapted to similar
fluorescent proteins (FPs), such as green fluorescent protein (GFP) and cyan
fluorescent protein (CFP). There are three critical considerations for using FPs
in C. difficile. (1) Choosing the right color: Blue and (especially) red are
preferred because C. difficile exhibits considerable yellow-green
autofluorescence. (2) Codon optimization: Most FP genes in general circulation
have a GC content of ~60 %, so they are not well expressed in low-GC bacteria.
(3) Fixing anaerobically grown cells prior to exposure to O2: The FPs under
consideration here are non-fluorescent when produced anaerobically because O2 is
required to introduce double bonds into the chromophore. Fixation prevents C.
difficile cells from becoming degraded during the several hours required for
chromophore maturation after cells are exposed to air. Fixation can probably be
omitted for studies in which maintaining cellular architecture is not important,
such as using mCherryOpt to monitor gene expression.
PMID- 27507334
TI - A Fluorescent Reporter for Single Cell Analysis of Gene Expression in Clostridium
difficile.
AB - Genetically identical cells growing under homogeneous growth conditions often
display cell-cell variation in gene expression. This variation stems from noise
in gene expression and can be adaptive allowing for division of labor and bet
hedging strategies. In particular, for bacterial pathogens, the expression of
phenotypes related to virulence can show cell-cell variation. Therefore,
understanding virulence-related gene expression requires knowledge of gene
expression patterns at the single cell level. We describe protocols for the use
of fluorescence reporters for single cell analysis of gene expression in the
human enteric pathogen Clostridium difficile, a strict anaerobe. The reporters
are based on modified versions of the human DNA repair enzyme O ( 6)-alkylguanine
DNA alkyltransferase, called SNAP-tag and CLIP-tag. SNAP becomes covalently
labeled upon reaction with O ( 6)-benzylguanine conjugated to a fluorophore,
whereas CLIP is labeled by O ( 6)-benzylcytosine conjugates. SNAP and CLIP
labeling is orthogonal allowing for dual labeling in the same cells. SNAP and
CLIP cassettes optimized for C. difficile can be used for quantitative studies of
gene expression at the single cell level. Both the SNAP and CLIP reporters can
also be used for studies of protein subcellular localization in C. difficile.
PMID- 27507335
TI - Clostridium difficile Adhesins.
AB - Clostridium difficile is responsible for a large spectrum of intestinal diseases
ranging from mild diarrhea to fatal colitis depending on the one hand on the
strain virulence and on the other on the host. The pathogenesis of C. difficile
infection could be seen as a three-step process that takes place after disruption
of the digestive microbiota by antibiotics: (1) contamination by and germination
of spores; (2) multiplication of vegetative cells in the colonic niche using
colonization factors; (3) production of the two toxins TcdA and TcdB and for some
strains an additional toxin, the binary toxin CDT. Several studies have been
performed to characterize the bacterial factors involved in the colonization step
and particularly adhesins.Here, we describe first the methods used to study C.
difficile adherence in vitro to epithelial cells and in vivo in animal model
intestinal tract, and second the methods used to demonstrate the adhesive
properties of surface proteins using Cwp66, GroEL, and FbpA as examples.
PMID- 27507336
TI - Intestinal Epithelial Cell Response to Clostridium difficile Flagella.
AB - Clostridium difficile is the bacterium responsible for most antibiotic-associated
diarrhea in North America and Europe. This bacterium, which colonizes the gut of
humans and animals, produces toxins that are known to contribute directly to
damage of the gut. It is known that bacterial flagella are involved in intestinal
lesions through the inflammatory host response. The C. difficile flagellin
recognizes TLR5 and consequently activates the NF-kappaB and the MAPK signaling
pathways which elicit the synthesis of pro-inflammatory cytokines. Increasing
interest on the role of C. difficile flagella in eliciting this cell response was
recently developed and the development of tools to study cell response triggered
by C. difficile flagella will improve our understanding of the pathogenesis of C.
difficile.
PMID- 27507337
TI - Isolating and Purifying Clostridium difficile Spores.
AB - The ability for the obligate anaerobe, Clostridium difficile to form a
metabolically dormant spore is critical for the survival of this organism outside
of the host. This spore form is resistant to a myriad of environmental stresses,
including heat, desiccation, and exposure to disinfectants and antimicrobials.
These intrinsic properties of spores allow C. difficile to survive long-term in
an oxygenated environment, to be easily transmitted from host-to-host, and to
persist within the host following antibiotic treatment. Because of the importance
of the spore form to the C. difficile life cycle and treatment and prevention of
C. difficile infection (CDI), the isolation and purification of spores are
necessary to study the mechanisms of sporulation and germination, investigate
spore properties and resistances, and for use in animal models of CDI. Here we
provide basic protocols, in vitro growth conditions, and additional
considerations for purifying C. difficile spores for a variety of downstream
applications.
PMID- 27507338
TI - Inducing and Quantifying Clostridium difficile Spore Formation.
AB - The Gram-positive nosocomial pathogen Clostridium difficile induces sporulation
during growth in the gastrointestinal tract. Sporulation is necessary for this
obligate anaerobe to form metabolically dormant spores that can resist antibiotic
treatment, survive exit from the mammalian host, and transmit C. difficile
infections. In this chapter, we describe a method for inducing C. difficile
sporulation in vitro. This method can be used to study sporulation and maximize
spore purification yields for a number of C. difficile strain backgrounds. We
also describe procedures for visualizing spore formation using phase-contrast
microscopy and for quantifying the efficiency of sporulation using heat
resistance as a measure of functional spore formation.
PMID- 27507339
TI - Characterization of Functional Prophages in Clostridium difficile.
AB - Bacteriophages (phages) are present in almost, if not all ecosystems. Some of
these bacterial viruses are present as latent "prophages," either integrated
within the chromosome of their host, or as episomal DNAs. Since prophages are
ubiquitous throughout the bacterial world, there has been a sustained interest in
trying to understand their contribution to the biology of their host. Clostridium
difficile is no exception to that rule and with the recent release of hundreds of
bacterial genome sequences, there has been a growing interest in trying to
identify and classify these prophages. Besides their identification in bacterial
genomes, there is also growing interest in determining the functionality of C.
difficile prophages, i.e., their capacity to escape their host and reinfect a
different strain, thereby promoting genomic evolution and horizontal transfer of
genes through transduction, for example of antibiotic resistance genes. There is
also some interest in using therapeutic phages to fight C. difficile
infections.The objective of this chapter is to share with the broader C.
difficile research community the expertise we developed in the study of C.
difficile temperate phages. In this chapter, we describe a general "pipeline"
comprising a series of experiments that we use in our lab to identify, induce,
isolate, propagate, and characterize prophages. Our aim is to provide readers
with the necessary basic tools to start studying C. difficile phages.
PMID- 27507341
TI - Phage Transduction.
AB - Bacteriophages mediate horizontal gene transfer through a mechanism known as
transduction. Phage transduction carried out in the laboratory involves a
bacterial donor and a recipient, both of which are susceptible to infection by
the phage of interest. Phage is propagated in the donor, concentrated, and
exposed transiently to recipient at different multiplicity of infection ratios.
Transductants are selected for the desired phenotype by culture on selective
medium. Here we describe transduction of ermB conferring resistance to
erythromycin by the C. difficile phage phiC2.
PMID- 27507340
TI - Induction and Purification of C. difficile Phage Tail-Like Particles.
AB - Due to the inherent limitations of conventional antibiotics for the treatment of
C. difficile infection (CDI), there is a growing interest in the development of
alternative treatment strategies. Both bacteriophages and R-type bacteriocins,
also known as phage tail-like particles (PTLPs), show promise as potential
antibacterial alternatives for treating CDI. Similar to bacteriophages, but
lacking a viral capsid and genome, PTLPs remain capable of killing target
bacteria. Here we describe our experience in the induction and purification of C.
difficile PTLPs. These methods have been optimized to allow production of
concentrated, non-contractile, and non-aggregated samples for both sensitivity
testing and structural electron microscopy studies.
PMID- 27507343
TI - Methods for Determining Transfer of Mobile Genetic Elements in Clostridium
difficile.
AB - Horizontal gene transfer by mobile genetic elements plays an important role in
the evolution of bacteria, allowing them to rapidly acquire new traits, including
antibiotic resistance. Mobile genetic elements such as conjugative and
mobilizable transposons make up a considerable part of the C. difficile genome.
While sequence analysis has identified a large number of these elements,
experimental analysis is required to demonstrate mobility and function. This
chapter describes the experimental methods utilized for determining function and
transfer of mobile genetic elements in C. difficile including detection of the
circular transfer intermediate and the analysis and confirmation of mobile
genetic element transfer to recipient cells.
PMID- 27507342
TI - Transfer of Clostridium difficile Genetic Elements Conferring Resistance to
Macrolide-Lincosamide-Streptogramin B (MLSB) Antibiotics.
AB - Molecular analysis is an important tool to investigate Clostridium difficile
resistance to macrolide-lincosamide-streptogramin B (MLSB). In particular, the
protocols described in this chapter have been designed to investigate the genetic
organization of erm(B)-containing elements and to evaluate the capability of
these elements to transfer in C. difficile recipient strains using filter mating
assay.
PMID- 27507344
TI - Investigating Transfer of Large Chromosomal Regions Containing the Pathogenicity
Locus Between Clostridium difficile Strains.
AB - The genomes of all sequenced Clostridium difficile isolates contain multiple
mobile genetic elements. The chromosomally located pathogenicity locus (PaLoc),
encoding the cytotoxins TcdA and TcdB, was previously hypothesized to be a mobile
genetic element; however, mobility was not demonstrated. Here we describe the
methods used to facilitate and detect the transfer of the PaLoc from a toxigenic
strain into non-toxigenic strains of C. difficile. Although the precise mechanism
of transfer has not yet been elucidated, a number of controls are described which
indicate transfer occurs via a cell-to-cell-mediated conjugation-like transfer
mechanism. Importantly, transfer of the PaLoc was shown to occur on large
chromosomal fragments of variable sizes, indicating that homologous recombination
is likely to be responsible for the insertion events.
PMID- 27507345
TI - An In Vitro Model of the Human Colon: Studies of Intestinal Biofilms and
Clostridium difficile Infection.
AB - The in vitro gut model is an invaluable research tool to study indigenous gut
microbiota communities, the behavior of pathogenic organisms, and the therapeutic
and adverse effect of antimicrobial administration on these communities. The
model has been validated against the intestinal contents of sudden death victims
to reflect the physicochemical and microbiological conditions of the proximal to
distal colon, and has been extensively used to investigate the interplay between
gut microbiota populations, antibiotic exposure, and Clostridium difficile
infection. More recently the gut model has been adapted to additionally model
intestinal biofilm. Here we describe the structure, assembly, and application of
the biofilm gut model.
PMID- 27507346
TI - MiniBioReactor Arrays (MBRAs) as a Tool for Studying C. difficile Physiology in
the Presence of a Complex Community.
AB - The commensal microbiome plays an important role in the dynamics of Clostridium
difficile infection. In this chapter, we describe minibioreactor arrays (MBRAs),
an in vitro cultivation system that we developed that allows for C. difficile
physiology to be assayed in the presence of complex fecal microbial communities.
The small size of the bioreactors within the MBRAs allows for dozens of reactors
to be run simultaneously and therefore several different variables can be tested
with limited time and cost. When coupled with experiments in animal models of C.
difficile infection, MBRAs can provide important insights into C. difficile
physiology and pathogenesis.
PMID- 27507347
TI - A Practical Method for Preparation of Fecal Microbiota Transplantation.
AB - Clostridium difficile is a challenging infection that can be difficult to treat
with antibiotic therapy. This chapter outlines the processing material for fecal
microbiota transplantation (FMT), also known as stool transplant. Fecal
transplantations are effective in treating recurrent C. difficile infection
(CDI). FMT uses a stool sample collected from a healthy, screened donor to
restore healthy microbiota in the colon of a patient with CDI for symptom
resolution. Here, we describe a rapid method for FMT preparation that uses
inexpensive and disposable materials.
PMID- 27507348
TI - Ion-Exchange Chromatography to Analyze Components of a Clostridium difficile
Vaccine.
AB - Ion-exchange (IEX) chromatography is one of many separation techniques that can
be employed to analyze proteins. The separation mechanism is based on a
reversible interaction between charged amino acids of a protein to the charged
ligands attached to a column at a given pH. This interaction depends on both the
pI and conformation of the protein being analyzed. The proteins are eluted by
increasing the salt concentration or pH gradient. Here we describe the use of
this technique to characterize the charge variant heterogeneities and to monitor
stability of four protein antigen components of a Clostridium difficile vaccine.
Furthermore, the IEX technique can be used to monitor reversion to toxicity for
formaldehyde-treated Clostridium difficile toxins.
PMID- 27507350
TI - Highly enantioselective construction of carbazole derivatives via [4+2]
cycloaddition of silyloxyvinylindoles and beta,gamma-unsaturated alpha
ketoesters.
AB - A highly efficient catalytic asymmetric [4+2] cycloaddition of
silyloxyvinylindoles with beta,gamma-unsaturated alpha-ketoesters has been
accomplished by an available chiral N,N'-dioxide/yttrium triflate complex. A
widespread range of carbazole derivatives were obtained in 47-98% yield with 86
99% ee under mild reaction conditions.
PMID- 27507349
TI - A Size-Exclusion Chromatography Method for Analysis of Clostridium difficile
Vaccine Toxins.
AB - High-performance size-exclusion chromatography (HPSEC or SEC) is a method that
can be applied to measure size distribution of proteins, including aggregates,
monomers, and fragments. In the biopharmaceutical industry the quantitation of
aggregates contained in biotherapeutics and protein-based vaccines is critical
given the potential impact on safety, immunogenicity, and efficacy. Hence,
aggregation analysis of therapeutic proteins or protein-based vaccine products is
almost always a requirement of regulatory agencies. SEC, also referred to as gel
filtration chromatography, separates molecules by size through a porous resin
stationary phase. Under isocratic flow small molecules are retained on the column
longer than large molecules. Here we describe the use of this SEC technique to
characterize aggregation levels for four different protein antigens for a
Clostridium difficile vaccine.
PMID- 27507351
TI - Annual charade makes a mockery of the pay process.
AB - Imagine if someone paid you for some expert advice, but before you had the chance
to say anything they told you what that advice should be. Pointless? I would say
so. You might be inclined to take the money, but would be entitled to question
the sanity or motives of the person handing over their cash.
PMID- 27507352
TI - Nursing Standard letter to PM: don't scrap bursary.
AB - Nursing Standard has urged prime minister Theresa May to rethink scrapping the
student bursary, warning that the move threatens the future of the profession.
PMID- 27507353
TI - Memories online.
AB - Nurses past and present are being encouraged to share their stories and
memorabilia for an online project charting the history of the NHS.
PMID- 27507354
TI - Unions censure Jeremy Hunt's rigid insistence on public sector pay restraint.
AB - Unions have condemned health secretary Jeremy Hunt's views that pay restraint for
nurses and other public sector workers continue.
PMID- 27507355
TI - Nurses urged to lobby NHS to fund HIV drug.
AB - Staff should lobby NHS England to fund a drug that can prevent HIV transmission,
according to a leading sexual health nurse.
PMID- 27507357
TI - Wales Safe Staffing Levels Act due in 2018.
AB - Hospitals in Wales will be legally obliged to implement safe nurse staffing
levels from April 2018, the Welsh Assembly has announced.
PMID- 27507359
TI - Nurses who faked blood sugar readings struck off.
AB - Three nurses who faked patients' blood sugar readings have been removed from the
Nursing and Midwifery Council register.
PMID- 27507360
TI - nursing.standard.com.
AB - 1 Nurses who have taken part in Widening Access Training scheme courses may be
eligible for national insurance and tax rebates. One nurse received a rebate of
L6,000, according to Moneysavingexpert.com . Read more: rcni.com/tax-rebate.
PMID- 27507361
TI - Revalidation renewal figures 'positive so far'.
AB - Nine out of ten nurses and midwives have renewed their Nursing and Midwifery
Council registration in the first 3 months of revalidation, figures reveal.
PMID- 27507362
TI - Former RCN Nurse of the Year to be honoured for her victim abuse training.
AB - Award-winning nurse Amanda Burston, pictured, will be feted for her work
supporting victims of domestic abuse at the Women of the Year lunch in October,
an event celebrating women's achievements. 'I am delighted to to be invited on
behalf of every victim of abuse,' she said. 'I accept every opportunity to keep
this vital conversation going.'
PMID- 27507363
TI - Nurses' tax rebate claims on the rise.
AB - Last week Nursing Standard reported on how potentially thousands of nurses and
other healthcare staff could be in line for rebates if they overpaid
contributions while studying on Widening Access Training (WAT) scheme courses.
PMID- 27507366
TI - Morning sickness.
AB - Essential facts Eight out of ten pregnant women are affected by nausea and
vomiting in pregnancy. It is one of the most common reasons for pregnant women
being admitted to hospital. Despite being known as morning sickness, symptoms can
occur at any time of the day or night. The severe form of nausea and vomiting in
pregnancy, hyperemesis gravidarum, is much rarer and affects up to 3% of pregnant
women. For most women, their symptoms improve or disappear by around week 14,
although for some it can last longer.
PMID- 27507367
TI - Call for guidance for women choosing C-sections.
AB - A study has highlighted the need for appropriate advice to be given to women
choosing to have a caesarean birth for non-medical reasons.
PMID- 27507368
TI - Too much TV causes lung blood clot deaths.
AB - Lung blood clots - also known as pulmonary embolisms - usually stem from clots in
the leg or pelvis after inactivity has slowed blood flow. It is particularly
dangerous if the clot travels to the lung and lodges in a small blood vessel.
PMID- 27507369
TI - Study calls for thyroid cancer test review.
AB - A study has called for a review of thyroid cancer follow-up practices following
concerns that unnecessary imaging tests are being carried out after primary
treatment.
PMID- 27507371
TI - Smoking less does not equal drinking more.
AB - The common conception that people giving up smoking drink more alcohol to
compensate has been questioned by a study.
PMID- 27507372
TI - Meet the school health pioneer.
AB - Nineteen years after becoming a school nurse I won the child health category in
the RCNi Nurse Awards for creating and developing a website called Health
Matters. Since becoming a school nurse in 1987, I have been challenged by how
difficult it is to engage young people in health and well-being. Young people
want a health service that is visible, accessible and confidential. But how can
we achieve that with the resources we have?'
PMID- 27507373
TI - Nurses join pollution fight.
AB - Most of us are aware of outdoor air pollution: spend time in any traffic-clogged
street, and you can taste the chemicals. Even spring days in the countryside can
be spoiled by ozone haze. But a report published earlier this year by the Royal
College of Physicians (RCP) and the Royal College of Paediatrics and Child Health
(RCPCH) revealed that air pollution is much more than an inconvenience - it is a
major health risk.
PMID- 27507374
TI - Sex, PrEP and the moral backlash.
AB - The news last week that the National AIDS Trust had won its High Court challenge
for Pre-exposure Prophylaxis (PrEP) to be provided by NHS England has made the
headlines.
PMID- 27507375
TI - Three approaches to safe staffing levels.
AB - We have a natural experiment emerging, with different UK countries looking at
different approaches to NHS nurse staffing. For example, in June, Scotland first
minister Nicola Sturgeon announced that Scotland will enshrine the use of
existing local nurse workforce planning tools in law. This was misrepresented in
some media coverage as being about legislated staffing levels, but it actually
legislates what was already common local practice: flexibility framed by tested
workforce tools, underpinned by professional judgement.
PMID- 27507376
TI - Mary Seacole statue campaign epitomises the strength of nursing.
AB - On the morning of 30 June in the grounds of St Thomas's Hospital in London,
overlooking the Thames and the Houses of Parliament, the statue of Mary Seacole
was unveiled.
PMID- 27507377
TI - Using folic acid-fortified flour should be mandatory policy.
AB - Research published last month states that pregnancy multivitamins do not
contribute anything towards boosting the health of mothers and babies.
PMID- 27507379
TI - Thanks for your help.
AB - On behalf of myself and the Mary Seacole Memorial Statue Appeal's Trustees,
thanks for your help and support in achieving our dream of a fitting monument to
Mary Seacole.
PMID- 27507381
TI - Key workers deserve better.
AB - Key workers 'affordable' housing is shocking treatment.
PMID- 27507382
TI - We need a full-scale campaign.
AB - I was glad you highlighted the housing crisis facing nursing. The situation has
never been this dire.
PMID- 27507383
TI - Readers' panel - Will expenses payments take the sting out of student loans?
AB - Our experts consider a hot topic of the day.
PMID- 27507387
TI - A Walk Through Dementia.
AB - Developed by charity Alzheimer's Research UK, and guided by people living with
different forms of dementia, this app aims to give an insight into the everyday
life of people suffering from dementia.
PMID- 27507384
TI - Nurses are leading the way in changing attitudes to dementia.
AB - My father and I had a pact - we would never repeat the daft things my grandmother
said. We just couldn't bear people laughing at her. My granny had always been
warm, witty and wise. Now in her eighties, she was in good form physically, but
her memory had left the building.
PMID- 27507388
TI - Student life - Role of neurodiverse nurses.
AB - Students and practitioners who are 'neurodiverse' - encompassing people who are
dyslexic and dyspraxic - make a positive contribution to patient care, and should
be celebrated.
PMID- 27507389
TI - In at the deep end with a drug-related wound.
AB - My first second-year placement was in the community, where I helped care for a
patient with an open wound on his inner thigh caused by repeated trauma from
intravenous drug use.
PMID- 27507390
TI - How to leave your job.
AB - 'Leaving a job is never a decision you should take lightly,' says Nick Simpson,
CEO of health recruitment agency MSI Group. 'Every nursing professional has
things about their job they find frustrating and daily tasks they may not
necessarily enjoy doing, but it's important to consider the positive aspects of
your current role before you make a decision.'
PMID- 27507391
TI - Clinical leaders of the future.
AB - Putting ideas for management improvement into practice is one of the core tenets
of the RCN's clinical leadership programme It's a transformational experience,'
says RCN interim head of education Anne Corrin. 'The change is personal and
professional.'
PMID- 27507392
TI - 'Don't wait, look for opportunities'.
AB - Steve Jamieson qualified as a nurse in 1986, and worked for the RCN for 17 years.
He was deputy director of nursing, managing a team of professional leads across
all areas of nursing, then chief executive of The Hospice of St Francis
Berkhamsted.
PMID- 27507393
TI - Effect of poverty on eye health and implications for nursing practice.
AB - Poverty is a global issue that affects the health and quality of life of millions
of people. It predisposes people to many health conditions, including sight loss
or blindness as a result of the immune system becoming compromised. Blindness is
common in areas of the world where there is extreme poverty. In the UK, poverty
has become a major social issue, contributing to many health problems, including
eye conditions. These eye conditions can result in sight loss if they are not
managed effectively. Psychosocial care is an essential aspect of patient care,
because poverty and sight loss are interrelated. Healthcare practitioners have a
significant role in the management and prevention of blindness. Blindness caused
by poverty is largely preventable, and health promotion is an important strategy
in care management.
PMID- 27507394
TI - Adverse drug reactions: classification, susceptibility and reporting.
AB - Adverse drug reactions (ADRs) are increasingly common and are a significant cause
of morbidity and mortality. Historically, ADRs have been classified as type A or
type B. Type A reactions are predictable from the known pharmacology of a drug
and are associated with high morbidity and low mortality. Type B reactions are
idiosyncratic, bizarre or novel responses that cannot be predicted from the known
pharmacology of a drug and are associated with low morbidity and high mortality.
Not all ADRs fit into type A and type B categories; therefore, additional
categories have been developed. These include type C (continuing), type D
(delayed use), and type E (end of use) reactions. Susceptibility to ADRs is
influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy.
Drug safety is reliant on nurses and other healthcare professionals being alert
to the possibility of ADRs, working with patients to optimise medicine use and
exercising vigilance in the reporting of ADRs through the Yellow Card Scheme.
PMID- 27507395
TI - Systematic reviews.
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 the purpose of
systematic reviews in nursing practice. It outlined the process of undertaking a
systematic review, and how this can benefit future research and clinical
practice.
PMID- 27507397
TI - Big picture.
AB - Joan Myers introduces her trust's BME strategy. Since its implementation, 71% of
BME staff at the trust believe career progression is possible.
PMID- 27507398
TI - Noisy nursing in the nick.
AB - 'It was interesting to see how the police and NHS staff work alongside each
other; two agencies with quite different agendas working under one roof'.
PMID- 27507396
TI - Matthew made my mum feel she wasn't 'just another patient'.
AB - Matthew Ridout gave outstanding care to my 85-year-old mother during her stay at
Ysbyty Ystrad Fawr hospital in Ystrad Mynach, south Wales following a stroke.
PMID- 27507399
TI - The great outdoors.
AB - Can a yearly camping trip help nurses improve their relationships with patients
with mental health problems? Emma Dorn and Danielle Hitch, writing in Mental
Health Practice, discuss the positive effect of a three-day annual camp organised
by mental health services.
PMID- 27507400
TI - The 'S' word.
AB - Sarah Cubbin, writing in Cancer Nursing Practice, notes that healthcare staff
found it difficult to bring up smoking cessation with patients with cancer who
were receiving palliative care and found it to be inappropriate when the patient
had limited life expectancy. The author notes that a solution for healthcare
professionals is to address the issue of smoking soon after diagnosis.
PMID- 27507401
TI - The value of e-rostering.
AB - Jacqueline Price, in Emergency Nurse, discusses her experience of an American e
rostering system. The system saved time for senior staff and provided an easier
way to manage leave and yet the author's colleagues viewed it unfavourably,
leading some to pursue jobs with more consistent shift systems. The author argues
that the systems must offer shift patterns that encourage work-life happiness and
better productivity.
PMID- 27507402
TI - Patients With Short Bowel on Narcotics During 2 Randomized Trials Have Abdominal
Complaints Independent of Teduglutide.
AB - BACKGROUND: Narcotic agents are frequently administered to manage increased
intestinal motility in patients with short bowel syndrome, but long-term use is
associated with gastrointestinal (GI) complaints. This analysis evaluated the
incidence of narcotic use and abdominal adverse events among patients with short
bowel syndrome receiving teduglutide. MATERIALS AND METHODS: Pooled data from
patients who received >=1 dose of teduglutide 0.05 mg/kg/d (n = 77) or placebo (n
= 59) in either of 2 randomized, double-blind, phase III studies were analyzed.
RESULTS: Of 136 patients, 52 (38%) received narcotics. GI adverse events occurred
more often among patients who received narcotics than among those who did not
(abdominal pain, 51% vs 21%; nausea, 42% vs 11%; abdominal distension, 17% vs 8%;
vomiting, 19% vs 6%). Logistic regression analysis indicated that the probability
of GI adverse events was significantly increased in patients with narcotic use (
P = .0009). In contrast, teduglutide treatment, as well as the interaction
between teduglutide and narcotic use, did not affect the probability of GI
adverse events. CONCLUSIONS: These results suggest that patients with short bowel
syndrome receiving narcotics have chronic GI complaints independent of
teduglutide treatment. Data included in this analysis were derived from
ClinicalTrials.gov NCT00081458 and NCT00798967 (EudraCT 2004-000438-35 and 2008
006193-15).
PMID- 27507403
TI - Polypropylene-based composite mesh versus standard polypropylene mesh in the
reconstruction of complicated large abdominal wall hernias: a prospective
randomized study.
AB - PURPOSE: To compare polypropylene mesh positioned onlay supported by omentum
and/or peritoneum versus inlay implantation of polypropylene-based composite mesh
in patients with complicated wide-defect ventral hernias. METHODS: This was a
prospective randomized study carried out on 60 patients presenting with
complicated large ventral hernia in the period from January 2012 to January 2016
in the department of Gastrointestinal Surgery unit and Surgical Emergency of the
Main Alexandria University Hospital, Egypt. Large hernia had an abdominal wall
defect that could not be closed. Patients were divided into two groups of 30
patients according to the type of mesh used to deal with the large abdominal wall
defect. RESULTS: The study included 38 women (63.3 %) and 22 men (37.7 %); their
mean age was 46.5 years (range, 25-70). Complicated incisional hernia was the
commonest presentation (56.7 %).The operative and mesh fixation times were longer
in the polypropylene group. Seven wound infections and two recurrences were
encountered in the propylene group. Mean follow-up was 28.7 months (2-48 months).
CONCLUSIONS: Composite mesh provided, in one session, satisfactory results in
patients with complicated large ventral hernia. The procedure is safe and
effective in lowering operative time with a trend of low wound complication and
recurrence rates.
PMID- 27507404
TI - Resolvin D2 Enhances Postischemic Revascularization While Resolving Inflammation.
AB - BACKGROUND: Resolvins are lipid mediators generated by leukocytes during the
resolution phase of inflammation. They have been shown to regulate the transition
from inflammation to tissue repair; however, it is unknown whether resolvins play
a role in tissue revascularization following ischemia. METHODS: We used a murine
model of hind limb ischemia (HLI), coupled with laser Doppler perfusion imaging,
microcomputed tomography, and targeted mass spectrometry, to assess the role of
resolvins in revascularization and inflammation resolution. RESULTS: In mice
undergoing HLI, we identified resolvin D2 (RvD2) in bone marrow and skeletal
muscle by mass spectrometry (n=4-7 per group). We also identified RvD2 in
skeletal muscle biopsies from humans with peripheral artery disease. Monocytes
were recruited to skeletal muscle during HLI and isolated monocytes produced RvD2
in a lipoxygenase-dependent manner. Exogenous RvD2 enhanced perfusion recovery in
HLI and microcomputed tomography of limb vasculature revealed greater volume,
with evidence of tortuous arterioles indicative of arteriogenesis (n=6-8 per
group). Unlike other treatment strategies for therapeutic revascularization that
exacerbate inflammation, RvD2 did not increase vascular permeability, but reduced
neutrophil accumulation and the plasma levels of tumor necrosis factor-alpha and
granulocyte macrophage colony-stimulating factor. In mice treated with RvD2,
histopathologic analysis of skeletal muscle of ischemic limbs showed more
regenerating myocytes with centrally located nuclei. RvD2 enhanced endothelial
cell migration in a Rac-dependent manner, via its receptor, GPR18, and Gpr18
deficient mice had an endogenous defect in perfusion recovery following HLI.
Importantly, RvD2 rescued defective revascularization in diabetic mice.
CONCLUSIONS: RvD2 stimulates arteriogenic revascularization during HLI,
suggesting that resolvins may be a novel class of mediators that both resolve
inflammation and promote arteriogenesis.
PMID- 27507405
TI - Predictors and Prognostic Significance of Right Ventricular Ejection Fraction in
Patients With Ischemic Cardiomyopathy.
AB - BACKGROUND: Decreased right ventricular (RV) ejection fraction (RVEF) portends
poor prognosis in patients with ischemic cardiomyopathy, and previous studies
have suggested an association between mitral regurgitation (MR) and RVEF. We
sought to evaluate this association and whether mitral valve repair or
replacement affects the relationship between RV function and mortality. METHODS:
We included 588 patients (mean age, 63+/-11 years; 75% male) with ischemic
cardiomyopathy who underwent cardiac magnetic resonance imaging between 2002 and
2008. Baseline characteristics, left ventricular ejection fraction, MR severity,
treatment modality, scar burden, and RVEF were assessed. Multivariable linear
regression and Cox proportional hazards models were used to assess the
association between MR and RVEF and between RVEF and mortality, respectively.
RESULTS: After adjustment for age, sex, left ventricular ejection fraction, right
bundle-branch block, and RV scar, MR severity was found to be associated
independently with RVEF. There were a total of 240 deaths during a median follow
up time of 5.7 years. After multivariable adjustment, every 10% decrease in RVEF
was associated with a 17% increased risk of death (P=0.008). Although decreasing
RVEF was associated with a poor prognosis in the nonrepair group (hazard ratio,
1.28; 95% confidence interval, 1.12-1.47; P<0.001), it was not associated with
death in the mitral valve repair or replacement group (P for interaction=0.046).
CONCLUSIONS: MR severity was found to be an independent predictor of RVEF, as
were right bundle-branch block, left ventricular ejection fraction, and the
presence of RV scar. Decreasing RVEF is associated with increased mortality in
patients with ischemic cardiomyopathy; however, this association may be mitigated
in patients who undergo mitral valve repair or replacement.
PMID- 27507406
TI - Return to the Workforce After First Hospitalization for Heart Failure: A Danish
Nationwide Cohort Study.
AB - BACKGROUND: Return to work is important financially, as a marker of functional
status and for self-esteem in patients developing chronic illness. We examined
return to work after first heart failure (HF) hospitalization. METHODS: By
individual-level linkage of nationwide Danish registries, we identified 21 455
patients of working age (18-60 years) with a first HF hospitalization in the
period from 1997 to 2012. Of these patients, 11 880 (55%) were in the workforce
before HF hospitalization and comprised the study population. We applied logistic
regression to estimate odds ratios for associations between age, sex, length of
hospital stay, level of education, income, comorbidity, and return to work.
RESULTS: One year after first HF hospitalization, 8040 (67.7%) returned to the
workforce, 2981 (25.1%) did not, 805 (6.7%) died, and 54 (0.5%) emigrated.
Predictors of return to work included younger age (18-30 versus 51-60 years; odds
ratio [OR], 3.12; 95% confidence interval [CI], 2.42-4.03), male sex (OR, 1.22;
95% CI, 1.12-1.34), and level of education (long-higher versus basic school; OR,
2.06; 95% CI, 1.63-2.60). Conversely, hospital stay >7 days (OR, 0.56; 95% CI,
0.51-0.62) and comorbidity including history of stroke (OR, 0.55; 95% CI, 0.45
0.69), chronic kidney disease (OR, 0.46; 95% CI, 0.36-0.59), chronic obstructive
pulmonary disease (OR, 0.62; 95% CI, 0.52-0.75), diabetes mellitus (OR 0.76; 95%
CI, 0.68-0.85), and cancer (OR, 0.49; 95% CI, 0.40-0.61) were all significantly
associated with lower chance of return to work. CONCLUSIONS: Patients in the
workforce before HF hospitalization had low mortality but high risk of detachment
from the workforce 1 year later. Young age, male sex, and a higher level of
education were predictors of return to work.
PMID- 27507407
TI - Development and characterization of chromosome segment substitution lines derived
from Oryza rufipogon in the genetic background of O. sativa spp. indica cultivar
9311.
AB - BACKGROUND: Wild rice (Oryza rufipogon) constitutes a primary gene source for
rice breed improvement. Chromosome segment substitution line (CSSL) for O.
rufipogon is a powerful tool for fine mapping of quantitative traits, new gene
discovery, and marker-assisted breeding. Thus, they provide a basis for a wide
range of genomic and genetic studies. RESULTS: In this study, a set of 198 CSSLs
were developed from a cross between recurrent parent indica var. 9311 and an O.
rufipogon donor parent; these were then genotyped using 313 polymorphic SSR
markers evenly distributed across the 12 rice chromosomes. On average, each CSSL
carried 2.16 introgressed segments, and the genetic distance of each segment was
about 6 cM. The segments collectively covered 84.9 % of the wild rice genome.
Based on these CSSLs, 25 QTLs involved in 10 agronomic traits were identified.
Seven CSSLs were subjected to a whole-genome single nucleotide polymorphism chip
assay and two QTLs, qSH4-1 and qDTH10-1, detected. In addition, a new QTL
associated with the heading date was detected in a 78-Kb region on chromosome 10,
thus proving the ability of these CSSLs to identify new QTLs and genes.
CONCLUSIONS: The newly developed CSSL population proved a useful tool for both
gene identification and whole-genome research of wild rice. These CSSL materials
will provide a foundation for rice variety improvement.
PMID- 27507408
TI - Phrenology between anthropology and neurology in a nineteenth-century collection
of skulls.
AB - The University of Padua has many legends about its cultural heritage. One of
these concerns a collection of eight skulls still preserved in the Hall of
Medicine at Bo Palace, near the old anatomy theatre built in 1545. It is said
that some famous professors of the University donated their bodies to medical
science, and the skulls were from these bodies. From multidisciplinary research,
both historical and anthropological, we have discovered that Francesco Cortese,
Professor of Medicine and Rector of the University, started this personal
collection of colleagues' skulls, although they had not donated their bodies to
science, so that he could make his own detailed phrenology study.
PMID- 27507409
TI - Effects of different fluid shear stress patterns on the in vitro degradation of
poly(lactide-co-glycolide) acid membranes.
AB - The applications of poly (lactide-co-glycolide) acid (PLGA) for coating or
fabricating polymeric biodegradable stents (BDSs) have drawn more attention. The
fluid shear stress has been proved to affect the in vitro degradation process of
PLGA membranes. During the maintenance, BDSs could be suffered different patterns
of fluid shear stress, but the effect of these different patterns on the whole
degradation process is unclear. In this study, in vitro degradation of PLGA
membranes was examined with steady, sinusoid, and squarewave fluid shear stress
patterns in 150 mL deionized water at 37 degrees C for 20 days, emphasizing on
the changes in the viscosity of the degradation solution, mechanical, and
morphological properties of the samples. The unsteady fluid shear stress with the
same average magnitude as the steady one accelerate the in vitro degradation
process of PLGA membranes in terms of maximum fluid shear stress and "window" of
effectiveness. Maximum fluid shear stress accelerates the in vitro degradation of
molecular fragments that diffused out in the solution while the "window" of
effectiveness affects too in the early stage. Besides, maximum fluid shear stress
and "window" of effectiveness accelerates the in vitro loss of tensile modulus
and ultimate strength of the PLGA membranes while the maximum fluid shear stress
plays the leading role in the decrease of tensile modulus at the early
degradation stage. This study could help advance the degradation design of PLGA
membranes under different fluid shear stress patterns for biomedical applications
like stents and drug release systems. (c) 2016 Wiley Periodicals, Inc. J Biomed
Mater Res Part A: 105A: 23-30, 2017.
PMID- 27507411
TI - [Pseudoxanthoma elasticum: A disorder with different manifestations].
AB - BACKGROUND: Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive
inheritable disorder characterized by progressive elastic fibre calcification.
CASE DESCRIPTION: Here we describe two patients with different presentations of
PXE. Patient A, an 11-year-old girl, visited the dermatologist because of yellow
papules (pseudoxanthomas) on the side of her neck. With the aid of a skin biopsy,
the dermatologist diagnosed PXE. Some years later, patient A developed symptoms
of intermittent claudication due to arterial calcifications. Supervised exercise
training diminished these symptoms. Patient B, a 55-year-old man, visited the
ophthalmologist due to recent onset of metamorphopsia. The ophthalmologist
discovered a subretinal haemorrhage and observed changes in the retina consistent
with PXE. Severe loss of vision was prevented by intraocular anti-VEGF
injections. Upon further investigation, pseudoxanthomas and arterial
calcifications were found. CONCLUSION: PXE is a rare monogenetic disorder with
dermatological, ocular and vascular manifestations. With these two case reports
we have illustrated how the initial clinical presentation and symptomatology may
vary widely.
PMID- 27507410
TI - Durable Responses with Brentuximab Vedotin in cHL.
AB - According to survival results from a phase II trial of brentuximab vedotin, 34
patients with relapsed or refractory classic Hodgkin lymphoma had a complete
response with this CD30-targeting antibody-drug conjugate; 13 remain in remission
5 years later.
PMID- 27507412
TI - [Infection prevention in newborns through maternal vaccination: current insights
and developments].
AB - - In the first few months of life, newborns are vulnerable to infections.-
Vaccination of the pregnant mother leads to transplacental antibody transfer,
resulting in the best possible protection of the newborn.- Maternal vaccination
has long been given for the prevention of tetanus in developing countries, and
for the prevention of pertussis and influenza in developed countries, such as the
United States, England and Belgium. These vaccinations give newborns good
protection and, to date, no adverse effects are known for the foetus or the
pregnancy.- Currently, phase 3 trials during pregnancy are ongoing following
maternal vaccination against group B streptococci and respiratory syncytial
virus. Here, again, no risks to mother or child have been reported.- Recently,
the Dutch Health Council advised that all pregnant women in the Netherlands be
vaccinated against pertussis in a vaccination programme.- This paper gives an
overview of effectiveness, safety and practicalities of maternal vaccination.
PMID- 27507413
TI - [Trends in suicidal behaviour in Dutch general practice, 1983-2013].
AB - OBJECTIVE: We investigated trends in suicidal behaviour as reported by Dutch
general practices from 1983 to 2013. Also, we analysed the relationship with
patient characteristics and with the financial crisis of 2008. DESIGN:
Retrospective observational study. METHOD: We estimated age-adjusted and gender
specific trends in suicides (342) and attempted suicides (1614), as registered in
1983-2013 under ICPC code P77 by 40 Dutch general practices participating in the
NIVEL Primary Care Database sentinel station. Secondary outcomes, on the basis of
supplementary questions in the GP Information System (Huisartsen Informatie
Systeem), were the relationship between suicidal behaviour, earlier treatments
and patient characteristics. Also, we analysed separate frequencies for the
periods 1983-2007 and 2008-2013. RESULTS: Join-point analyses revealed a
significant rise in male suicides from 2008 (b = 0.32, SE = 0.1, p = 0.008), and
an increase in male suicide attempts since 2009 (b = 0.19, SE = 0.04, p < 0.001).
Female suicidal behaviour showed a steady decrease in 1989-2013: b = -0.03, SE =
0.007, p < 0.0001 for female suicide, b = -0.02, SE = 0.002, p < 0.001 for female
attempts. Almost half of the suicidal patients had visited their GP one month
before the event. In 31% of these patients, the GP had recognized suicidal
behaviour. CONCLUSIONS: Since 2008, there was a rise in the male suicide rate
while female suicide behaviour has continued to decline. Training in the early
recognition of suicide ideation in depressive patients might improve suicide
prevention in primary care.
PMID- 27507414
TI - [Psychiatric manifestations due to abnormal glucocorticoid levels].
AB - This clinical case presentation describes the disease trajectory in two patients
who presented with psychiatric symptoms as a result of abnormal serum
glucocorticoid levels. One case involves a 58-year-old man with hypercortisolism,
the other case concerns a 55-year-old woman with hypocortisolism. In both cases
there was a considerable diagnostic delay in recognizing the underlying adrenal
gland pathology. Abnormal glucocorticoid levels, caused by endocrine disorders,
often results in psychiatric symptoms. Delay in diagnosis may have adverse
consequences. Hyper- or hypocortisolism should be considered in patients who
present with an atypical presentation of psychiatric symptoms. Moreover, the
absence of specific physical signs or symptoms at first presentation in such
patients does not exclude an underlying endocrinological cause. Therefore,
physical and psychiatric reassessment of such patients should be considered at
regular intervals.
PMID- 27507416
TI - Application of Deep Eutectic Solvent Modified Cotton as a Sorbent for Online
Solid-Phase Extraction and Determination of Trace Amounts of Copper and Nickel in
Water and Biological Samples.
AB - Deep eutectic solvent (DES) was used as the extractant to improve the extraction
properties of cotton. DES of choline chloride-urea (ChCl-urea) was prepared and
immobilized on the surface of cotton fibers. The resulting sorbent was packed on
a microcolumn, and a flow injection flame atomic absorption spectrometry was
designed for the online separation and determination of trace amounts of copper
and nickel. Various parameters affecting the extraction recovery of analytes such
as pH, sample volume, sample loading rate, nature, volume, concentration, and
flow rate of eluent were investigated and optimized. Under the optimum
conditions, the method showed good linearity in the concentration range of 0.25
50.0 and 4.0-125.0 MUg L-1 with the coefficient of determination (r 2) of 0.9991
and 0.9990 for copper and nickel, respectively. The method was very sensitive
with the detection limits (defined as 3Sb/m) of 0.05 and 0.60 MUg L-1 for Cu and
Ni, respectively. It was successfully applied for the determination of Cu and Ni
in water and biological samples. The accuracy of the method was evaluated through
the recovery experiments and independent analysis by electrothermal atomic
absorption spectrometry.
PMID- 27507417
TI - Facilitators and barriers to treatment with haemodialysis among persons in mid
adulthood: an interpretative phenomenological analysis.
AB - BACKGROUND: The quality of life of persons on haemodialysis (HD) is often limited
by the restrictions imposed by their medical regimen. These restrictions may
negatively influence patients' adherence to their treatment. Therefore, in an
effort to improve patients' adherence to treatment, there is the need to explore
the patients' perceptions of facilitators and barriers in relation to their
experience of HD. AIM: The purpose of the study was to explore the perceived
barriers and facilitators of the HD experience of persons in mid-adulthood.
PARTICIPANTS AND DESIGN: A qualitative design was used. Semistructured interviews
were conducted with seven participants in the mid-adulthood phase (40-65 years).
The transcribed texts were analysed using an Interpretative Phenomenological
Analysis approach. RESULTS: Three main themes were identified from the analysis:
'social network outside the renal unit', 'the renal setting as a context' and
'qualities relating to staff'. Facilitators identified include: support from
family and work colleagues, caring and knowledgeable staff and consultation with
patients when planning out the treatment schedule. Barriers to treatment include:
discomfort with the needling process, intrusion of HD on family time, lack of
privacy in the renal unit and staff that do not take their concerns seriously.
CONCLUSION: This study demonstrated the need for healthcare professionals to
allocate time and space, where persons on HD may discuss personal issues that
relate to their care experience in a private care setting. By identifying and
exploring the barriers and facilitators of patients on haemodialysis, healthcare
professionals may formulate individualised care plans which may improve patients'
adherence to their HD treatment.
PMID- 27507415
TI - Time to antibiotic therapy and outcome in bacterial meningitis: a Danish
population-based cohort study.
AB - BACKGROUND: Community-acquired bacterial meningitis (CABM) is a life-threatening
disease and timing of antibiotic therapy remains crucial. We aimed to analyse the
impact of antibiotic timing on the outcome of CABM in a contemporary cohort.
METHODS: We conducted a population-based cohort study based on chart reviews of
all adult cases (>16 years of age) of CABM in North Denmark from 1998 to 2014
excluding patients given pre-hospital parenteral antibiotics. We used modified
Poisson regression analyses to compute the adjusted risk ratio (adj. RR) with 95
% confidence intervals (CIs) for in-hospital mortality and unfavourable outcome
at discharge by time after arrival to hospital to adequate antibiotic therapy.
RESULTS: We identified 195 adults with CABM of whom 173 patients were eligible
for further analyses. The median door-to-antibiotic time was 2.0 h (interquartile
range (IQR) 1.0-5.5). We observed increased adjusted risk ratios for in-hospital
mortality of 1.6 (95 % CI 0.8-3.2) and an unfavourable outcome at discharge of
1.5 (95 % CI 1.0-2.2, p = 0.03) when treatment delays exceeded 6 h versus
treatment within 2 h of admission. These findings corresponded to adjusted risk
ratios of in-hospital mortality of 1.1 per hour of delay (95 % CI 0.8-1.5) and an
unfavourable outcome at discharge of 1.1 per hour of delay (95 % CI 1.0-1.3)
within the first 6 h of admission. Some patients (31 %) were diagnosed after
admission and had more delays in antibiotic therapy and correspondingly increased
in-hospital mortality (30 vs 14 %, p = 0.01) and unfavourable outcome (62 vs 37
%, p = 0.002). CONCLUSIONS: Delay in antibiotic therapy was associated with
unfavourable outcome at discharge.
PMID- 27507418
TI - Effects of Antibiotics on the Growth and Physiology of Chlorophytes,
Cyanobacteria, and a Diatom.
AB - The occurrence of antibiotics in surface waters has been reported worldwide with
concentrations ranging from ng L-1 to low ug L-1 levels. During environmental
risk assessments, effects of antibiotics on algal species are assessed using
standard test protocols (e.g., the OECD 201 guideline), where the cell number
endpoint is used as a surrogate for growth. However, the use of photosynthetic
related endpoints, such as oxygen evolution rate, and the assessment of effects
on algal pigments could help to inform our understanding of the impacts of
antibiotics on algal species. This study explored the effects of three major
usage antibiotics (tylosin, lincomycin, and trimethoprim) on the growth and
physiology of two chlorophytes (Desmodesmus subspicatus and Pseudokirchneriella
subcapitata), a cyanobacteria (Anabaena flos-aquae), and a diatom (Navicula
pelliculosa) using a battery of parameters, including cell density, oxygen
evolution rate, total chlorophyll content, carotenoids, and the irradiance
photosynthesis relationship. The results indicated that photosynthesis of
chlorophytes was a more sensitive endpoint than growth (i.e., EC50 derived based
on the effects of tylosin on the growth of D. subspicatus was 38.27 umol L-1
compared with an EC50 of 17.6 umol L-1 based on photosynthetic rate), but the
situation was reversed when testing cyanobacteria and the diatom (i.e., EC50
derived based on the effects of tylosin on the growth of A. flos-aquae was 0.06
umol L-1; EC50 0.33 umol L-1 based on photosynthetic rate). The pigment contents
of algal cells were affected by the three antibiotics for D. subspicatus.
However, in some cases, pigment content was stimulated for P. subcapitata, N.
pelliculosa, and A. flos-aquae. The light utilization efficiency of chlorophytes
and diatom was decreased markedly in the presence of antibiotics. The results
demonstrated that the integration of these additional endpoints into existing
standardised protocols could provide useful insights into the impacts of
antibiotics on algal species.
PMID- 27507419
TI - Breath analysis for colorectal cancer screening.
PMID- 27507420
TI - Base-Biased Evolution of Disease-Associated Mutations in the Human Genome.
AB - Understanding the evolution of disease-associated mutations is fundamental to
analyze pathogenetics of diseases. Mutation, recombination (by GC-biased gene
conversion, gBGC), and selection have been known to shape the evolution of
disease-associated mutations, but how these evolutionary forces work together is
still an open question. In this study, we analyzed several human large-scale
datasets (1000 Genomes, ESP6500, ExAC and ClinVar), and found that base-biased
mutagenesis generates more GC->AT than AT->GC mutations, while gBGC promotes the
fixation of AT->GC mutations to balance the impact of base-biased mutation on
genome. Due to this effect of gBGC, purifying selection removes more deleterious
AT->GC mutations than GC->AT from population, but many high-frequency (fixed and
nearly fixed) deleterious AT->GC mutations are remained possibly due to high
genetic load. As a special subset, disease-associated mutations follow this
evolutionary rule, in which disease-associated GC->AT mutations are more enriched
in rare mutations compared with AT->GC, while disease-associated AT->GC are more
enriched in mutations with high frequency. Thus, we presented a base-biased
evolutionary framework that explains the base-biased generation and accumulation
of disease-associated mutations in human populations.
PMID- 27507421
TI - Isolation and genotyping of Acanthamoeba spp. from Acanthamoeba meningitis/
meningoencephalitis (AME) patients in India.
AB - BACKGROUND: Acanthamoeba spp. are free-living ubiquitous protozoans capable of
causing Acanthamoeba meningitis/meningoencephalitis (AME) of the central nervous
system in humans. Acanthamoeba spp. are divided into 20 different genotypes (T1
T20) on the basis of variation in nucleotide sequences of the 18S rRNA gene. The
objective of this study was to identify the genotypes of Acanthamoeba spp. in
patients of Acanthamoeba meningitis/meningoencephalitis (AME) using 18S rRNA gene
based PCR assay. The present study provides information regarding the involvement
of the most prevalent and predominant genotype of Acanthamoeba spp. in
Acanthamoeba meningitis/meningoencephalitis infections in India. METHODS:
Cerebrospinal fluid (CSF) was collected from 149 clinically suspected
Acanthamoeba meningitis/meningoencephalitis (AME) patients reporting to the
outpatient department/causality services of the Neurosciences Centre, AIIMS, New
Delhi, India during the past five years. Samples were inoculated onto 2 % non
nutrient agar plates overlaid with E. coli and incubated at 30 degrees C for 14
days. Among 149 suspected patients, ten were found culture-positive for
Acanthamoeba spp. out of which six isolates were established in axenic culture
for molecular analysis. DNA was isolated and a PCR assay was performed for
amplification of the Diagnostic fragment 3 (DF3) (~280 bp) region of the 18S rRNA
gene from axenic culture of six Acanthamoeba spp. isolates. Rns genotyping was
performed on the basis of the variation in nucleotide sequences of DF3 region of
the 18S rRNA gene. RESULTS: In the phylogenetic analysis, all of the six
Acanthamoeba spp. isolates were found to belong to genotype T4. The sequence
homology search for these six isolates in the NCBI databank showed homology with
the available strains of Acanthamoeba spp. The newly generated sequences are
available in the GenBank database under accession numbers KT004416-KT004421.
CONCLUSIONS: In the present study, genotype T4 was found as the most prevalent
and predominant genotype in Acanthamoeba meningitis/ meningoencephalitis
infections. Hence further studies are needed to develop optimal therapeutic
strategy against Acanthamoeba spp. of genotype T4 to combat against the
infections.
PMID- 27507422
TI - Neural modulation of directed forgetting by valence and arousal: An event-related
potential study.
AB - Intentional forgetting benefits memory by removing no longer needed information
and promoting processing of more relevant materials. This study sought to
understand how the behavioural and neurophysiological representation of
intentional forgetting would be impacted by emotion. We took a novel approach by
examining the unique contribution of both valence and arousal on emotional
directed forgetting. Participants completed an item directed forgetting task for
positive, negative, and neutral words at high and lower levels of arousal while
brain activity was recorded using electroencephalography (EEG). Behaviourally,
recognition of to-be-remembered (TBR) and to-be-forgotten (TBF) items varied as a
function of valence and arousal with reduced directed forgetting for high
arousing negative and neutral words. In the brain, patterns of frontal and
posterior activation in response to TBF and TBR cues respectively replicated
prior EEG evidence to support involvement of inhibitory and selective rehearsal
mechanisms in item directed forgetting. Interestingly, emotion only impacted cue
related posterior activity, which varied depending on specific interactions
between valence and arousal. Together, results suggest that the brain handles
valence and arousal differently and highlights the importance of considering in a
collective manner the multidimensional nature of emotion in experimentation.
PMID- 27507423
TI - Activation of the prefrontal cortex by unilateral transcranial direct current
stimulation leads to an asymmetrical effect on risk preference in frames of gain
and loss.
AB - Previous brain imaging and brain stimulation studies have suggested that the
dorsolateral prefrontal cortex may be critical in regulating risk-taking
behavior, although its specific causal effect on people's risk preference remains
controversial. This paper studied the independent modulation of the activity of
the right and left dorsolateral prefrontal cortex using various configurations of
transcranial direct current stimulation. We designed a risk-measurement table and
adopted a within-subject design to compare the same participant's risk preference
before and after unilateral stimulation when presented with different frames of
gain and loss. The results confirmed a hemispheric asymmetry and indicated that
the right dorsolateral prefrontal cortex has an asymmetric effect on risk
preference regarding frames of gain and loss. Enhancing the activity of the right
dorsolateral prefrontal cortex significantly decreased the participants' degree
of risk aversion in the gain frame, whereas it increased the participants' degree
of risk aversion in the loss frame. Our findings provide important information
regarding the impact of transcranial direct current stimulation on the risk
preference of healthy participants. The effects observed in our experiment
compared with those of previous studies provide further evidence of the effects
of hemispheric and frame-dependent asymmetry. These findings may be helpful in
understanding the neural basis of risk preference in humans, especially when
faced with decisions involving possible gain or loss relative to the status quo.
PMID- 27507424
TI - Rats showing low and high sensitization of frequency-modulated 50-kHz
vocalization response to amphetamine differ in amphetamine-induced brain Fos
expression.
AB - Individuals predisposed to addiction constitute a minority of drug users, in both
humans and animal models of the disorder, but there are no established
characteristics that would allow identifying them beforehand. Our studies
demonstrate that sensitization of rat 50-kHz ultrasonic vocalization (USV)
response to amphetamine shows marked inter-individual diversity but substantial
intra-individual stability. Low sensitization of the response shows relevance to
the acquisition of self-administration of this drug and hence might be of
predictive value regarding the risk of addiction. We compared amphetamine-induced
Fos expression in 16 brain regions considered important for the development of
addiction between rats preselected for low and high sensitization of the response
and next given nine daily amphetamine doses followed by a 2-week withdrawal and
final amphetamine challenge. Ventral tegmental area and nucleus accumbens shell
Fos-positive nuclei counts correlated positively with 50-kHz USV response to the
challenge in high-sensitized rats. Compared to those in amphetamine-untreated
controls, Fos-positive nuclei counts were significantly and markedly (2-6 times)
higher in 12 regions in high-sensitized rats, whereas in low-sensitized rats they
were significantly higher in the cingulate cortex and dorsomedial striatum only.
The difference in the counts between the latter two subsets reached statistical
significance in dorsomedial and dorsolateral striatum and three out of four
cortical regions studied. The fact that the diversification was most distinct in
dorsal striatum that plays a critical role in the transition from controlled to
compulsive drug intake suggests that the USV-based categorization may be related
to divergent vulnerability of rats to AMPH addiction.
PMID- 27507425
TI - Structural basis for cytokinin production by LOG from Corynebacterium glutamicum.
AB - "Lonely guy" (LOG) has been identified as a cytokinin-producing enzyme in plants
and plant-interacting fungi. The gene product of Cg2612 from the soil-dwelling
bacterium Corynebacterium glutamicum was annotated as an LDC. However, the facts
that C. glutamicum lacks an LDC and Cg2612 has high amino acid similarity with
LOG proteins suggest that Cg2612 is possibly an LOG protein. To investigate the
function of Cg2612, we determined its crystal structure at a resolution of 2.3 A.
Cg2612 functions as a dimer and shows an overall structure similar to other known
LOGs, such as LOGs from Arabidopsis thaliana (AtLOG), Claviceps purpurea (CpLOG),
and Mycobacterium marinum (MmLOG). Cg2612 also contains a "PGGXGTXXE" motif that
contributes to the formation of an active site similar to other LOGs. Moreover,
biochemical studies on Cg2612 revealed that the protein has phosphoribohydrolase
activity but not LDC activity. Based on these structural and biochemical studies,
we propose that Cg2612 is not an LDC family enzyme, but instead belongs to the
LOG family. In addition, the prenyl-binding site of Cg2612 (CgLOG) comprised
residues identical to those seen in AtLOG and CpLOG, albeit dissimilar to those
in MmLOG. The work provides structural and functional implications for LOG-like
proteins from other microorganisms.
PMID- 27507427
TI - Genetic gradient of a host-parasite pair along a river persisted ten years
against physical mobility: Baltic Salmo salar vs. Gyrodactylus salaris.
AB - The Atlantic salmon, Salmo salar L., in the Tornio River in the Northern Baltic
Sea basin accommodates a monogenean ectoparasite, Gyrodactylus salaris. The aim
of the study was to understand the population structure of apparently co-adapted
host-parasite system: no parasite-associated mortality has been reported. The
parasite burden among salmon juveniles (parr) was monitored along 460km of the
river in 2000-2009. Among the parr, 33.0% were infected (nfish=1913). The genetic
structure of the parasite population was studied by sequencing an anonymous
nuclear DNA marker (ADNAM1, three main genotypes) and mitochondrial CO1 (three
clades, six haplotypes). During the ten years, the parasite population was
strongly and stably genetically differentiated among up- and downstream nurseries
(nADNAM1=411, FST=0.579; nCO1=443, FST=0.534). Infection prevalence among the
smolts migrating to sea was higher than in the sedentary parr populations (82.2%,
nfish=129). The spatial differentiation observed among the sedentary juveniles
was reflected temporally in the smolt run: parasite genotypes dominating the
upper part of the river arrived later than downstream dwellers (medians June 4
and June 2) to the trap 7km from the river mouth. The nuclear and mitochondrial
markers were in stable disequilibrium which was not relaxed in the contact zone
or among the smolts where the parasite clones often met on individual fish. Only
five parasite specimens on smolts (nworms=217) were putative recent sexual
recombinants. The contribution of extant salmon hatcheries into the infection was
negligible. The host salmon population in Tornio River is known to show
significant spatial differentiation (FST=0.022). The stable spatial genetic
structure of the parasite against the high physical mobility suggested a
possibility of local co-adaptation of the host-parasite subpopulations.
PMID- 27507428
TI - The CD4(+) T cell methylome contributes to a distinct CD4(+) T cell
transcriptional signature in Mycobacterium bovis-infected cattle.
AB - We hypothesised that epigenetic regulation of CD4(+) T lymphocytes contributes to
a shift toward a dysfunctional T cell phenotype which may impact on their ability
to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and
Reduced Representation Bisulfite Sequencing identified 193 significantly
differentially expressed genes and 760 differentially methylated regions (DMRs),
between CD4(+) T cells from M. bovis infected and healthy cattle. 196 DMRs were
located within 10 kb of annotated genes, including GATA3 and RORC, both of which
encode transcription factors that promote TH2 and TH17 T helper cell subsets
respectively. Gene-specific DNA methylation and gene expression levels for the
TNFRSF4 and Interferon-gamma genes were significantly negatively correlated
suggesting a regulatory relationship. Pathway analysis of DMRs identified
enrichment of genes involved in the anti-proliferative TGF-beta signaling pathway
and TGFB1 expression was significantly increased in peripheral blood leukocytes
from TB-infected cattle. This first analysis of the bovine CD4(+) T cell
methylome suggests that DNA methylation directly contributes to a distinct gene
expression signature in CD4(+) T cells from cattle infected with M. bovis.
Specific methylation changes proximal to key inflammatory gene loci may be
critical to the emergence of a non-protective CD4(+) T cell response during
mycobacterial infection in cattle.
PMID- 27507429
TI - Carbon nanorings with inserted acenes: breaking symmetry in excited state
dynamics.
AB - Conjugated cycloparaphenylene rings have unique electronic properties being the
smallest segments of carbon nanotubes. Their conjugated backbones support
delocalized electronic excitations, which dynamics is strongly influenced by
cyclic geometry. Here we present a comparative theoretical study of the
electronic and vibrational energy relaxation and redistribution in photoexcited
cycloparaphenylene carbon nanorings with inserted naphthalene, anthracene, and
tetracene units using non-adiabatic excited-state molecular dynamics simulations.
Calculated excited state structures reflect modifications of optical selection
rules and appearance of low-energy electronic states localized on the acenes due
to gradual departure from a perfect circular symmetry. After photoexcitation, an
ultrafast electronic energy relaxation to the lowest excited state is observed on
the time scale of hundreds of femtoseconds in all molecules studied.
Concomitantly, the efficiency of the exciton trapping in the acene raises when
moving from naphthalene to anthracene and to tetracene, being negligible in
naphthalene, and ~60% and 70% in anthracene and tetracene within the first 500 fs
after photoexcitation. Observed photoinduced dynamics is further analyzed in
details using induced molecular distortions, delocatization properties of
participating electronic states and non-adiabatic coupling strengths. Our results
provide a number of insights into design of cyclic molecular systems for
electronic and light-harvesting applications.
PMID- 27507430
TI - Large-scale molecular dynamics simulation: Effect of polarization on thrombin
ligand binding energy.
AB - Molecular dynamics (MD) simulations lasting 500 ns were performed in explicit
water to investigate the effect of polarization on the binding of ligands to
human alpha-thrombin based on the standard nonpolarizable AMBER force field and
the quantum-derived polarized protein-specific charge (PPC). The PPC includes the
electronic polarization effect of the thrombin-ligand complex, which is absent in
the standard force field. A detailed analysis and comparison of the results of
the MD simulation with experimental data provided strong evidence that intra
protein, protein-ligand hydrogen bonds and the root-mean-square deviation of
backbone atoms were significantly stabilized through electronic polarization.
Specifically, two critical hydrogen bonds between thrombin and the ligand were
broken at approximately 190 ns when AMBER force field was used and the number of
intra-protein backbone hydrogen bonds was higher under PPC than under AMBER. The
thrombin-ligand binding energy was computed using the molecular mechanics Poisson
Boltzmann surface area (MM/PBSA) method, and the results were consistent with the
experimental value obtained using PPC. Because hydrogen bonds were unstable, it
was failed to predict the binding affinity under the AMBER force field.
Furthermore, the results of the present study revealed that differences in the
binding free energy between AMBER and PPC almost comes from the electrostatic
interaction. Thus, this study provides evidence that protein polarization is
critical to accurately describe protein-ligand binding.
PMID- 27507431
TI - Assessing cardiac and liver iron overload in chronically transfused patients with
sickle cell disease.
AB - Transfusional iron overload represents a substantial challenge in the management
of patients with sickle cell disease (SCD) who receive chronic or episodic red
blood cell transfusions. Iron-induced cardiomyopathy is a leading cause of death
in other chronically transfused populations but rarely seen in SCD. Study
objectives were to: (i) examine the extent of myocardial and hepatic siderosis
using magnetic resonance imaging (MRI) in chronically transfused SCD patients,
and (ii) evaluate the relationship between long-term (over the 5 years prior to
enrolment) mean serum ferritin (MSF), spot-ferritin values and liver iron content
(LIC) measured using MRI and liver biopsy. Thirty-two SCD patients (median age 15
years) with transfusional iron overload were recruited from two U.S.
institutions. Long-term MSF and spot-ferritin values significantly correlated
with LIC by MRI-R2* (r = 0.77, P < 0.001; r = 0.82, P < 0.001, respectively). LIC
by MRI-R2* had strong positive correlation with LIC by liver biopsy (r = 0.98, P
< 0.001) but modest inverse correlation with cardiac MRI-T2* (r = -0.41, P =
0.02). Moderate to severe transfusional iron overload in SCD was not associated
with aberrations in other measures of cardiac function based on echocardiogram or
serum biomarkers. Our results suggest that SCD patients receiving chronic
transfusions may not demonstrate significant cardiac iron loading irrespective of
ferritin trends, LIC and erythropoiesis suppression.
PMID- 27507433
TI - Controlled creation and displacement of charged domain walls in ferroelectric
thin films.
AB - Charged domain walls in ferroelectric materials are of high interest due to their
potential use in nanoelectronic devices. While previous approaches have utilized
complex scanning probe techniques or frustrative poling here we show the creation
of charged domain walls in ferroelectric thin films during simple polarization
switching using either a conductive probe tip or patterned top electrodes. We
demonstrate that ferroelectric switching is accompanied - without exception - by
the appearance of charged domain walls and that these walls can be displaced and
erased reliably. We ascertain from a combination of scanning probe microscopy,
transmission electron microscopy and phase field simulations that creation of
charged domain walls is a by-product of, and as such is always coupled to,
ferroelectric switching. This is due to the (110) orientation of the tetragonal
(Pb,Sr)TiO3 thin films and the crucial role played by the limited conduction of
the LSMO bottom electrode layer used in this study. This work highlights that
charged domain walls, far from being exotic, unstable structures, as might have
been assumed previously, can be robust, stable easily-controlled features in
ferroelectric thin films.
PMID- 27507432
TI - "A novel highly stable and injectable hydrogel based on a conformationally
restricted ultrashort peptide".
AB - Nanostructures including hydrogels based on peptides containing non protein amino
acids are being considered as platform for drug delivery because of their
inherent biocompatibility and additional proteolytic stability. Here we describe
instantaneous self-assembly of a conformationally restricted dipeptide,
LeuDeltaPhe, containing an alpha,beta-dehydrophenylalanine residue into a highly
stable and mechanically strong hydrogel, under mild physiological aqueous
conditions. The gel successfully entrapped several hydrophobic and hydrophilic
drug molecules and released them in a controlled manner. LeuDeltaPhe was highly
biocompatible and easily injectable. Administration of an antineoplastic drug
entrapped in the gel in tumor bearing mice significantly controlled growth of
tumors. These characteristics make LeuDeltaPhe an attractive candidate for
further development as a delivery platform for various biomedical applications.
PMID- 27507434
TI - Impact of a standardized rapid response system on outcomes in a large healthcare
jurisdiction.
AB - AIM: To assess the impact of a standardized rapid response system (RRS)
implemented across a large health care jurisdiction on reducing serious adverse
events, hospital mortality and unexpected deaths. METHOD: We conducted an
interrupted time series (2007-2013) population-based study in the state of New
South Wales (NSW), Australia to evaluate the impact of introducing a statewide
standardized RRS (the between-the-flags [BTF] system) which employed a five
component intervention strategy. We studied 9,799,081 admissions in all 232
public hospitals in NSW. We studied changes in trends for annual rates of
multiple key patient-centered outcomes before and after its introduction.
RESULTS: Before the BTF system (2007-2009), there was a progressive decrease in
mortality, cardiac arrest rates, cardiac arrests related mortality, and failure
to rescue rates, but no changes in mortality rate among low mortality diagnostic
related group (LMDRGs) patients. After the BTF program (2010-2013), the same
trends continued for all outcomes with an overall (2013 vs 2007) 46% reduction in
cardiac arrest rates; a 54% reduction in cardiac arrest related mortality rates;
a 19% reduction in hospital mortality; a 35% decrease in failure to rescue rates
(all Ps<0.001) over seven-years. In addition, there was a new 20% (p<0.001)
mortality reduction among LMDRG patients (2013 vs 2007). CONCLUSIONS: The BTF
program was associated with continued decrease in the overall cardiac arrests
rates, deaths after cardiac arrest, hospital mortality and failure to rescue. In
addition, among patients in the LMDRC group, it induced a new and significant
post-intervention reduction in mortality which was never reported before.
PMID- 27507436
TI - Sexual rights and the public health: why moral judgements matter.
PMID- 27507435
TI - Mechanistic characterization of nitrite-mediated neuroprotection after
experimental cardiac arrest.
AB - Nitrite acts as an ischemic reservoir of nitric oxide (NO) and a potent S
nitrosating agent which reduced histologic brain injury after rat asphyxial
cardiac arrest (ACA). The mechanism(s) of nitrite-mediated neuroprotection remain
to be defined. We hypothesized that nitrite-mediated brain mitochondrial S
nitrosation accounts for neuroprotection by reducing reperfusion reactive oxygen
species (ROS) generation. Nitrite (4 MUmol) or placebo was infused IV after
normothermic (37 degrees C) ACA in randomized, blinded fashion with evaluation of
neurologic function, survival, brain mitochondrial function, and ROS. Blood and
CSF nitrite were quantified using reductive chemiluminescence and S-nitrosation
by biotin switch. Direct neuroprotection was verified in vitro after 1 and 4 h
neuronal oxygen glucose deprivation measuring neuronal death with inhibition
studies to examine mechanism. Mitochondrial ROS generation was quantified by live
neuronal imaging using mitoSOX. Nitrite significantly reduced neurologic
disability after ACA. ROS generation was reduced in brain mitochondria from
nitrite- versus placebo-treated rats after ACA with congruent preservation of
brain ascorbate and reduction of ROS in brain sections using immuno-spin
trapping. ATP generation was maintained with nitrite up to 24 h after ACA.
Nitrite rapidly entered CSF and increased brain mitochondrial S-nitrosation.
Nitrite reduced in vitro mitochondrial superoxide generation and improved
survival of neurons after oxygen glucose deprivation. Protection was maintained
with inhibition of soluble guanylate cyclase but lost with NO scavenging and
ultraviolet irradiation. Nitrite therapy results in direct neuroprotection from
ACA mediated by reductions in brain mitochondrial ROS in association with protein
S-nitrosation. Neuroprotection is dependent on NO and S-nitrosothiol generation,
not soluble guanylate cyclase.
PMID- 27507437
TI - Why take part in personalised cancer research? Patients' genetic misconception,
genetic responsibility and incomprehension of stratification-an empirical-ethical
examination.
AB - Therapeutic misconception is a well-known challenge for informed decision-making
for cancer research participants. What is still missing, is a detailed
understanding of the impact of "personalised" treatment research (e.g. biomarkers
for stratification) on research participants. For this, we conducted the first
longitudinal empirical-ethical study based on semi-structured interviews with
colorectal cancer patients (n = 40) enrolled in a biomarker trial for
(neo)adjuvant treatment, analysing the patients' understanding of and
perspectives on research and treatment with qualitative methods. In addition to
therapeutic misconception based on patients' confusion of research and treatment,
and here triggered by misled motivation, information paternalism or
incomprehension, we identified genetic misconception and genetic responsibility
as new problematic issues. Patients mainly were not aware of the major research
aim of future stratification into responders and non-responders nor did they
fully acknowledge this as the aim for personalised cancer research. Thus, ethical
and practical reflection on informed decision-making in cancer treatment and
research should take into account the complexity of lay interpretations of modern
personalised medicine. Instead of very formalistic, liability-oriented informed
consent procedures, we suggest a more personalised communication approach to
inform and motivate patients for cancer research.
PMID- 27507438
TI - Charge-based separation of particles and cells with similar sizes via the wall
induced electrical lift.
AB - The separation of particles and cells in a uniform mixture has been extensively
studied as a necessity in many chemical and biomedical engineering and research
fields. This work demonstrates a continuous charge-based separation of
fluorescent and plain spherical polystyrene particles with comparable sizes in a
psi-shaped microchannel via the wall-induced electrical lift. The effects of both
the direct current electric field in the main-branch and the electric field ratio
in between the inlet branches for sheath fluid and particle mixture are
investigated on this electrokinetic particle separation. A Lagrangian tracking
method based theoretical model is also developed to understand the particle
transport in the microchannel and simulate the parametric effects on particle
separation. Moreover, the demonstrated charge-based separation is applied to a
mixture of yeast cells and polystyrene particles with similar sizes. Good
separation efficiency and purity are achieved for both the cells and the
particles.
PMID- 27507439
TI - Reaction pathway mechanism of thermally induced isomerization of 9,12-linoleic
acid triacylglycerol.
AB - BACKGROUND: To clarify the formation mechanism of trans linoleic acid isomers in
edible oils during the heating process, trilinolein and trilinoelaidin, as
representative oils, were placed in glass ampoules and sealed before heating at
180, 240 and 320 degrees C. The glass ampoules were removed at regular time
intervals, and the contents were analyzed by infrared spectroscopy. The samples
were then subjected to derivatization into their methyl esters for gas
chromatographic analysis. RESULTS: Analysis results show that 9c,12c and 9t,12t
fatty acids from trilinolein and trilinoelaidin molecules undergo chemical bond
rotation, migration and degradation, leading to the formation of non-conjugated
linoleic acids (NLAs), conjugated linoleic acids (CLAs) and aldehydes. The
formation rate of isomers from the 9c,12c fatty acid is higher than that of the
9t,12t fatty acid. The production of aldehydes increases with heating temperature
and time. The isomerization pathways involved in the formation of NLAs and CLAs
during heating are clearly presented. CONCLUSION: These findings suggest possible
pathways of NFA and CFA formation from heated trilinolein and trilinoelaidin,
complement the mechanistic studies previously published in the literature, and
provide a theoretical basis for future control of the quality and safety of fats
and oils. (c) 2016 Society of Chemical Industry.
PMID- 27507440
TI - Complex enzyme hydrolysis releases antioxidative phenolics from rice bran.
AB - In this study, phenolic profiles and antioxidant activity of rice bran were
analyzed following successive treatment by gelatinization, liquefaction and
complex enzyme hydrolysis. Compared with gelatinization alone, liquefaction
slightly increased the total amount of phenolics and antioxidant activity as
measured by ferric reducing antioxidant power (FRAP) and oxygen radical
absorbance capacity (ORAC) assays. Complex enzyme hydrolysis significantly
increased the total phenolics, flavonoids, FRAP and ORAC by 46.24%, 79.13%,
159.14% and 41.98%, respectively, compared to gelatinization alone. Furthermore,
ten individual phenolics present in free or soluble conjugate forms were also
analyzed following enzymatic processing. Ferulic acid experienced the largest
release, followed by protocatechuic acid and then quercetin. Interestingly, a
major proportion of phenolics existed as soluble conjugates, rather than free
form. Overall, complex enzyme hydrolysis releases phenolics, thus increasing the
antioxidant activity of rice bran extract. This study provides useful information
for processing rice bran into functional beverage rich in phenolics.
PMID- 27507441
TI - Pressurized water extraction of isoflavones by experimental design from soybean
flour and Soybean Protein Isolate.
AB - A Doehlert experimental design was conducted and surface response methodology was
used to determine the effect of temperature, contact time and solid liquid ratio
on isoflavone extraction from soybean flour or Soybean Protein Isolate in
pressurized water system. The optimal conditions conducted gave an extraction
yield of 85% from soybean flour. For Soybean Protein Isolate compared to soybean
flour, the isoflavone extraction yield is 61%. This difference could be explained
by higher aglycon content, while aglycon appears to be the least extracted
isoflavone by pressurized water. The solid liquid ratio in the ASE cell was the
overriding factor in obtaining high yields with both soybean products, while
temperature has less influence. A high temperature causes conversion of the
malonyls-glucosides and glucosides isoflavone derivatives into glucosides or
aglycons forms. pressurized water extraction showed a high solubilization of
protein material up to 95% of inserted Soybean Protein Isolate.
PMID- 27507442
TI - Textural and cargo release attributes of trisodium citrate cross-linked starch
hydrogel.
AB - An alkaline starch suspension was charged with citric acid and incubated for
different durations (0, 8.5 or 17h). The suspension was then supplemented with
caffeine and gelatinized to fabricate hydrogels which were subsequently stored
for varying periods (0, 24 or 48h). Charging of the well-dissolved alkaline
starch suspension with citric acid decreased at first both the flow index and
consistency coefficient (K); however, starch cross-linking over time by the
generated trisodium citrate increased the K value. The latter also inhibited gel
syneresis and increased its water-holding capacity. Trisodium citrate did not
nonetheless influence the gel hardness except for the sample incubated for
maximum duration and stored for the longest period. The amount of the caffeine
released from hydrogel decreased by citrate cross-linking and was higher at
neutral pH than pH 2.0. Fourier-transform infra-red spectroscopy suggested that
caffeine was enclosed within the gel network via non-covalent interactions.
PMID- 27507443
TI - Highly sensitive determination of antimony in food by resonance Rayleigh
scattering-energy transfer between grapheme oxide and I3(.).
AB - Sb(III) was reduced to SbH3 gas and introduced to the I3(-)-grapheme oxide (GO)
or I3(-)-silver nanorod (AgNR)-Victoria blue B (VBB) solutions. Resonance
Rayleigh scattering energy transfer (RRS-ET) occurred between the donor GO and
the acceptor I3(-) due to the overlap between the absorption peak of I3(-) and
RRS peak of GO. When I3(-) was reduced by SbH3, RRS-ET weakened and the RRS
intensity enhanced. The increased RRS intensity was linear to Sb concentration in
the range of 2.1-376.6MUg/L. In the I3(-)-AgNR-VBB solution, I3(-) combined with
VBB to form VBB-I3 and there was a weak surface-enhanced Raman scattering (SERS)
effect. When SbH3 reduced I3(-), the SERS intensity increased due to the release
of SERS active VBB. The enhanced SERS intensity was linear for Sb concentration
in the range of 8.4-292.9MUg/L. The RRS-ET method was applied for determination
of Sb in food with satisfactory results.
PMID- 27507444
TI - Antioxidant, nutritional and functional characteristics of wheat bread enriched
with ground flaxseed hulls.
AB - Antioxidant capacity, nutritional and functional quality of wheat bread
supplemented with 1-5% flaxseed hull (FH) were studied. Analyses of the
chemically-extractable fraction show that supplementation with 5% of FH increased
(compared to control) phenolics content (by 93%), radicals scavenging ability (by
176%) and reducing power (by 220%). Furthermore, phenolic antioxidants were
bioaccessible in vitro (samples after simulated digestion). Fortification had no
significant influence on rapidly and slowly digestible starch, in vitro starch
digestibility and values of expected glycemic index; however, a decrease (up to
8%) of relative proteins digestibility was determined. Enrichment decreased loaf
volume and increased crumb hardness. The results from sensory evaluation show
that the incorporation of FH had a slightly unfavorable effect on bread sensory
properties but ensured satisfactory consumer acceptability. In view of these
facts, it is concluded that flaxseed hulls may be a beneficial food additive.
PMID- 27507445
TI - Purification and characterization of a naringinase from a newly isolated strain
of Bacillus amyloliquefaciens 11568 suitable for the transformation of
flavonoids.
AB - An intracellular naringinase from Bacillus amyloliquefaciens 11568 isolated from
soil was purified, identified, and characterized. The sodium dodecyl sulfate
polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the purified enzyme
gave a single protein band corresponding to a molecular mass of 32kDa. The
optimum pH and temperature for naringinase and its alpha-l-rhamnosidase and beta
d-glucosidase activities were pH 7.5 and 45 degrees C, respectively. The enzymes
were stable below 45 degrees C between pH 3.5 and 8.5. The Km and the Vmax of the
isolated naringinase were 0.95mmol/L and 3847.3mmol/(L.min), respectively. The
isolated naringinase was capable of hydrolyzing naringin, neohesperidin, and
other glycosides. Additionally, a concentration of 4U/mL of the enzyme in citrus
juice was sufficient to remove the naringin and alleviate the bitterness of the
juice. These results provide an in-depth insight into the structure of the
naringinase and the hydrolysis of naringin and other flavonoids.
PMID- 27507446
TI - Polyvinylpolypyrrolidone reduces cross-reactions between antibodies and phenolic
compounds in an enzyme-linked immunosorbent assay for the detection of ochratoxin
A.
AB - Ochratoxin A (OTA) is a fungal metabolite and putative carcinogen which can
contaminate a variety of foods such as cereals, wine, and nuts. Commercial ELISA
kits are known to give false-positive results for OTA concentrations when
phenolic compounds are present. Pistachios represent a food matrix rich in
phenolic compounds potentially contaminated with OTA, and were used to model OTA
cross-reactivity. Polyvinylpolypyrrolidone (PVPP) was incorporated during
extraction of OTA using a commercial ELISA protocol. HPLC methods were used to
confirm that PVPP does not interact with OTA and levels of gallic acid and
catechin remaining in pistachio extracts decreased with increasing PVPP
application. Cross-reactivity of extracts also decreased with increasing PVPP
application, and color loss was used as an indicator of anthocyanin removal.
Incorporating PVPP into ELISA protocols allows for the continued use of rapid
immunological methods in food matrices containing phenolic compounds.
PMID- 27507447
TI - Impact of acid and oxidative modifications, single or dual, of sorghum starch on
biodegradable films.
AB - The objective of this study was to evaluate the effects of acid and oxidation
modifications on sorghum starch, as well as the effect of dual modification of
starch on the physical, morphological, mechanical, and barrier properties of
biodegradable films. The acid modification was performed with 3% lactic acid and
the oxidation was performed with 1.5% active chlorine. For dual modification, the
acid modification was performed first, followed by oxidation under the same
conditions as above. Both films of the oxidized starches, single and dual, had
increased stiffness, providing a higher tensile strength and lower elongation
when compared to films based on native and single acid modified starches.
However, the dual modification increased the water vapor permeability of the
films without changing their solubility. The increase in sorghum starch
concentration in the filmogenic solution increased the thickness, water vapor
permeability, and elongation of the films.
PMID- 27507449
TI - Development of a workflow for screening and identification of alpha-amylase
inhibitory peptides from food source using an integrated Bioinformatics-phage
display approach: Case study - Cumin seed.
AB - The main objective of this study was to develop an efficient workflow to discover
alpha-amylase inhibitory peptides from cumin seed. A total of 56 unknown peptides
was initially found in the cumin seed protein hydrolysate. They were subjected to
2 different in silico screenings and 6 peptides were shortlisted. The peptides
were then subjected to in vitro selection using phage display technique and 3
clones (CSP3, CSP4 and CSP6) showed high affinity in binding alpha-amylase. These
clones were subjected to the inhibitory test and only CSP4 and CSP6 exhibited
high inhibitory activity. Therefore, these peptides were chemically synthesized
for validation purposes. CSP4 exhibited inhibition of bacterial and human
salivary alpha-amylases with IC50 values of 0.11 and 0.04MUmol, respectively,
whereas CSP6 was about 0.10 and 0.15MUmol, respectively. Results showed that the
strength of each protocol has been successfully combined as deemed fit to enhance
the alpha-amylase inhibitor peptide discovery.
PMID- 27507448
TI - Green extraction of polyphenols from whole pomegranate fruit using cyclodextrins.
AB - Pomegranate is a source of bioactive phytochemicals. The objective of this study
was the derivation of a sustainable method to exploit the whole fruit, both
edible and non-edible parts, as a source of polyphenols. Pomegranate peel
contains a 10-fold higher phenolic content than the pulp. The fruit was freeze
dried and the resulting dry matter was extracted with solid-liquid percolation
equipment using non-toxic and eco-friendly extraction solvents: either deionized
water or aqueous solutions of cyclodextrins. Cyclodextrins (CDs) are known
molecular encapsulators and our results prove enhancement of the extraction of
pomegranate polyphenols by 20%. In order to examine the formation of inclusion
complexes between CD's and polyphenols of the extract, polyphenols were isolated
using solid-phase extraction. NMR studies with the purified extracts and the
individual CDs confirmed inclusion complex formation in water. Pomegranate liquid
extracts may be used as raw materials for several end-users in the food, cosmetic
and pharmaceutical industries.
PMID- 27507450
TI - Determination of metrafenone in vegetables by matrix solid-phase dispersion and
HPLC-UV method.
AB - A simple method for determination of metrafenone in vegetables by matrix solid
phase dispersion (MSPD) and HPLC was developed. All vegetable samples were
extracted with dichloromethane, and then the extracts were directly separated on
a reversed-phase column with isocratic elution without a cleanup step. The
linearity of metrafenone was good with the concentration between 0.005 and
5mg/kg, and the limit of detection (LOD) of the metrafenone was 0.002mg/kg. The
recoveries ranged from 86.5% to 104.8% with the relative standard deviations
(RSDs) in the range of 2.1-7.9% (n=6). The results indicated that the method was
simple, rapid, highly sensitive and suitable for the determination of metrafenone
in vegetables.
PMID- 27507451
TI - Amplified electrochemical determination of maltol in food based on graphene oxide
wrapped tin oxide@carbon nanospheres.
AB - The study presents a new approach for rapid and ultrasensitive detection of
maltol using a glassy carbon electrode (GCE) modified with graphene oxide-wrapped
tin oxide@carbon nanospheres (SnO2@C@GO). The morphological and components
properties of SnO2@C@GO nanocomposites were investigated by means of X-ray
diffraction spectroscopy, Raman spectroscopy, field emission scanning electron
microscopy, high resolution transmission electron microscopy, and electrochemical
impedance spectroscopy. SnO2@C@GO nanocomposite on a GCE had a synergetic effect
on the electrochemical oxidation of maltol by means of square wave voltammetry.
Under the optimum conditions, anodic peak current response of maltol was linear
with its concentration in the range of 80nM-10MUM, and a detection limit of 12nM
was achieved for maltol. The experiment results presented that the method showed
good selectivity, sensitivity, reproducibility, and long-term stability, as well
as excellent potential for use as an ideal inexpensive voltammetric method
applicable for complex food matrices.
PMID- 27507452
TI - Structure and pasting properties of alkaline-treated phosphorylated cross-linked
waxy maize starches.
AB - The objectives of this study were to determine the stability of cross-linked
bonds of starch at different pH values and their effects on the pasting property
of waxy maize starch cross-linked by 0.05% and 3% sodium trimetaphosphate/sodium
tripolyphosphate. The cross-linked waxy maize starch (CLWMS) was slurried (40%,
w/w) and subjected to alkali treatments of pH 9, 10, 11, and 12 at 40 degrees C
for 4h. The phosphorus in 3% CLWMS decreased with increasing pH and remained
unchanged in 0.05% CLWMS for all pH treatments. Decreased settling volumes
indicated the reduction of swelling power for the alkali-treated CLWMS at pH 11
and 12. The (31)P NMR spectra of 3% CLWMS at pH 12 showed decreased cyclic
monostarch phosphate, monostarch monophosphate, and monostarch diphosphate, but
significantly increased distarch monophosphate. Alkali treatments of
phosphorylated cross-linked starches offer a way to manipulate the rheological
properties of cross-linked starch for desired food applications.
PMID- 27507453
TI - Mercury accumulation of three Lactarius mushroom species.
AB - Accumulation, distribution and potential dietary intake of mercury accumulated by
mushrooms of Lactarius species L. delicious, L. volemus and L. deterrimus were
studied in the Pomerania region of Poland. In total, 212 fruiting bodies and 106
underlying topsoil samples were analyzed. Analysis indicated that the
concentrations of Hg were at low levels both in mushrooms and forest topsoils for
a majority of the locations investigated. L. volemus that grew in soils with only
a slightly elevated contamination (0.11+/-0.07mgkg(-1) of dried soil), very
efficiently accumulated Hg in fruiting bodies and concentration levels were at
3.7+/-1.3mgkg(-1) of dry biomass in caps and at 1.9+/-0.9mgkg(-1) of dry biomass
in stipes. Consumption of mushrooms foraged from the Sobowidz forest, which is
close to a foundry using ferrous and non-ferrous metals could result in a Hg
intake that exceeds the current statutory limits.
PMID- 27507454
TI - Leptosperin is a distinct and detectable fluorophore in Leptospermum honeys.
AB - New Zealand manuka (Leptospermum scoparium) honey exhibits two unique
fluorescence signatures that distinguish it from other honey types. One of these
is the MM1 fluorescence marker (270-365nm excitation-emission) which we show is
due to a Leptospermum nectar-derived compound, leptosperin. Synthetic or honey
purified leptosperin not only displayed an identical fluorescence spectrum, but
supplementation of leptosperin into clover or artificial honeys generated the MM1
fluorescence signature. There was a quenching effect of the honey matrix on
leptosperin fluorescence but otherwise leptosperin was chemically stable over
prolonged storage at 37 degrees C. Leptosperin was also present in the woody
fruited Australian Leptospermum species at elevated concentrations but virtually
absent in Leptospermum subtenue suggesting its elevated expression developed
following the mid-Miocene separation of the genus. These findings suggest that
fluorescence spectroscopy could offer a rapid and high-throughput screening
method for identification of Leptospermum honeys using the MM1 fluorescence
marker.
PMID- 27507455
TI - Analyses of effects of alpha-cembratrien-diol on cell morphology and
transcriptome of Valsa mali var. mali.
AB - The objective of this work was to study the underlying mechanisms of growth
inhibition of Valsa mali var. mali, the causative pathogen of apple tree canker
disease, by alpha-cembratrien-diol. The half maximal inhibitory concentration of
alpha-cembratrien-diol against V. mali var. mali is 18.0mg/L. Treatment of V.
mali var. mali with alpha-cembratrien-diol resulted in various mycelial and
cellular abnormalities, and the up- and down-regulation of 94 and 170
differentially expressed genes, respectively. Gene Ontology term enrichment
analysis revealed that alpha-cembratrien-diol substantially altered the
expression of genes involved in the redox process, tetrapyrrole binding, coenzyme
binding, heme binding, and iron binding. Kyoto Encyclopedia of Genes and Genomes
enrichment analysis also showed significant enrichment of specific metabolic
pathways involving the set of differentially expressed genes. The present study
will assist in the development of alternative alpha-cembratrien-diol-based
biological control agents and ultimately facilitate organic apple production.
PMID- 27507456
TI - Stability-increasing effects of anthocyanin glycosyl acylation.
AB - This review comprehensively summarizes the existing knowledge regarding the
chemical implications of anthocyanin glycosyl acylation, the effects of acylation
on the stability of acylated anthocyanins and the corresponding mechanisms.
Anthocyanin glycosyl acylation commonly refers to the phenomenon in which the
hydroxyl groups of anthocyanin glycosyls are esterified by aliphatic or aromatic
acids, which is synthetically represented by the acylation sites as well as the
types and numbers of acyl groups. Generally, glycosyl acylation increases the in
vitro and in vivo chemical stability of acylated anthocyanins, and the mechanisms
primarily involve physicochemical, stereochemical, photochemical, biochemical or
environmental aspects under specific conditions. Additionally, the acylation
sites as well as the types and numbers of acyl groups influence the stability of
acylated anthocyanins to different degrees. This review could provide insight
into the optimization of the stability of anthocyanins as well as the application
of suitable anthocyanins in food, pharmaceutical and cosmetic industries.
PMID- 27507457
TI - Salinity effect on nutritional value, chemical composition and bioactive
compounds content of Cichorium spinosum L.
AB - Soil salinization is an increasing problem for many areas throughout the world
that renders prohibitive vegetables and crop production in general. In the
present study, Cichorium spinosum L. plants were grown under saline conditions in
order to evaluate chemical composition and bioactive compounds content of their
leaves. Salinity increase resulted in significant changes of macro and micro
nutrients content (nutritional value, sugars, fatty acids, minerals, ascorbic
acid and tocopherols), whereas the concentration of phenolic compounds was not
significantly affected. Chicoric and 5-O-caffeoylquinic acid were the most
abundant phenolic acids. In contrast, antioxidant activity and mineral
composition were beneficially affected by mid-to-high and high salinity levels.
In conclusion, C. spinosum can be cultivated under saline conditions without
compromising the quality of the final product, especially in semi-arid areas
where irrigation water is scarce and/or of low quality due to high content of
NaCl (coastal areas or areas where underground water is saline).
PMID- 27507458
TI - Accumulation of carotenoids and expression of carotenogenic genes in peach fruit.
AB - To understand better the regulatory mechanism of the carotenoid accumulation, the
expression profile of relevant carotenoid genes and metabolites were compared
between two peach cultivars with different colors during fruit development.
Meanwhile, the change pattern of carotenoid content and expression of carotenoid
metabolic genes in peaches after harvest in response to blue light were also
investigated. As compared to the yellow fleshed-cultivar 'Jinli', lower
carotenoid levels were observed in skin and pulp in white peach cultivar
'Hujing', which might be explained by differentially expression of PpCCD4 gene.
With respect to 'Jinli', the carotenoid accumulation during fruit development in
fruit skin was partially linked with the transcriptional regulation of PpFPPS,
PpGGPS, PpLCYB and PpCHYB. However, in the pulp, the accumulation might be also
associated with the increased transcriptions of PpPDS, along with the above four
genes. Blue light treatment induced carotenoid accumulation in 'Jinli' peaches
during storage. In addition, the treated-fruit displayed higher expression of all
the eight genes analysed with a lesser extent on PpCCD4, which suggested that the
much more increased carotenoid synthesis rate could result in the higher
carotenoid content in blue light-treated fruit. The results presented herein
contribute to further elucidating the regulatory mechanism of carotenoid
accumulation in peach fruit.
PMID- 27507459
TI - A rapid method for the simultaneous quantification of the major tocopherols,
carotenoids, free and esterified sterols in canola (Brassica napus) oil using
normal phase liquid chromatography.
AB - A normal phase high performance liquid chromatography (HPLC) method was developed
to simultaneously quantify several prominent bioactive compounds in canola oil
vis. alpha-tocopherol, gamma-tocopherol, delta-tocopherol, beta-carotene, lutein,
beta-sitosterol, campesterol and brassicasterol. The use of sequential diode
array detection (DAD) and tandem mass spectrometry (MS/MS) allowed direct
injection of oils, diluted in hexane without derivatisation or saponification,
greatly reducing sample preparation time, and permitting the quantification of
both free sterols and intact sterol esters. Further advantages over existing
methods included increased analytical selectivity, and a chromatographic run time
substantially less than other reported normal phase methods. The HPLC-DAD-MS/MS
method was applied to freshly extracted canola oil samples as well as
commercially available canola, palm fruit, sunflower and olive oils.
PMID- 27507460
TI - Continuous method to determine the trypsin inhibitor activity in soybean flour.
AB - The determination of trypsin inhibitor (TI) activity is of importance to evaluate
the nutritional value of soybean flours. An analytical method, which involves a
continuous spectrophotometric rate determination for trypsin activity against the
substrate N-benzoyl-DL-arginine p-nitroanilide, is proposed as an alternative to
the standard discontinuous assay. Stopping the reaction with acetic acid and a
centrifugation/filtration step to decrease turbidity are not required, thus
reducing costs and sample preparation time. The TI activity of different flour
samples, determined by both assays, demonstrated to be statistically comparable,
irrespective of the TI concentration level. The coefficients of variation of the
novel method did not exceed 8% at any concentration level. The curves of progress
reaction showed a non-linear behavior in samples without TI. A reduction of
incubation time from 10min to 2min increased the method sensitivity and extended
its linear range. A more economical, faster and simpler assay was developed.
PMID- 27507461
TI - Evaluation of health potential of nutritionally enriched Kodo millet (Eleusine
coracana) grown in Himachal Pradesh, India.
AB - In this study, Kodo millet grains were phytochemically investigated for their
nutritional and antioxidant potential for their use as functional foods.
Methanolic extracts of grains showed higher phenolic content and antioxidant
activity. TLC studies of the extracted polyphenols from kodo millet showed the
predominant presence of ferulic acid and cinnamic acid in the millet. Further
quantification of these polyphenols was done by using HPLC, analysing ferulic
acid and cinnamic acid. Antagonistic spectrum of the polyphenols extracted showed
inhibition against four bacterial test indicators viz. Staphylococcus aureus,
Leuconostoc mesenteroides, Bacillus cereus and Enterococcus faecalis proving its
antimicrobial action. The grains of kodo millet grains taken under study were
found to posses' high protein, carbohydrates, minerals, crude fibers, polyphenols
and antioxidants thus can be used as a good source of nutrition with additional
health benefits.
PMID- 27507462
TI - One-step competitive lateral flow biosensor running on an independent
quantification system for smart phones based in-situ detection of trace Hg(II) in
tap water.
AB - In this study, a one-step lateral flow biosensor (LFB) has been developed,
optimized and validated for quantitative detection of Hg(II) in water. In the
measurement principle, just one T-rich ssDNA probe (TSP) for the specific binding
process was successfully employed in the competitive LFB based methods. The
concept of an independent quantification system was realized using a cresol red
dot as an external standard, which effectively eliminates false negative results.
Under optimized conditions, the limit of detection for Hg(II) was 4nM; high
selectivity towards Hg(II) and extraordinary device-to-device repeatability of
the LFB were achieved. Furthermore, Hg(II) from tap water samples was analyzed,
and the results were confirmed by ICP-MS. The interference from other components
in the real samples could be neglected during the analysis. The approach provides
a simple, sensitive, and practical tool for the detection of trace Hg(II) in tap
water, showing great promise for in-situ applications.
PMID- 27507463
TI - Validation of a high-performance size-exclusion chromatography method to
determine and characterize beta-glucans in beer wort using a triple-detector
array.
AB - Beer wort beta-glucans are high-molecular-weight non-starch polysaccharides of
that are great interest to the brewing industries. Because glucans can increase
the viscosity of the solutions and form gels, hazes, and precipitates, they are
often related to poor lautering performance and beer filtration problems. In this
work, a simple and suitable method was developed to determine and characterize
beta-glucans in beer wort using size exclusion chromatography coupled with a
triple-detector array, which is composed of a light scatterer, a viscometer, and
a refractive-index detector. The method performances are comparable to the
commercial reference method as result from the statistical validation and enable
one to obtain interesting parameters of beta-glucan in beer wort, such as the
molecular weight averages, fraction description, hydrodynamic radius, intrinsic
viscosity, polydispersity and Mark-Houwink parameters. This characterization can
be useful in brewing science to understand filtration problems, which are not
always explained through conventional analysis.
PMID- 27507464
TI - Rapid identification of the botanical and entomological sources of honey using
DNA metabarcoding.
AB - Honey is generated by various bee species from diverse plants, and because the
value of different types of honey varies more than 100-fold, it is a target for
fraud. This paper describes a protocol that employs DNA metabarcoding of three
gene regions (ITS2, rbcLa, and COI) to provide an inexpensive tool to
simultaneously deliver information on the botanical and entomological origins of
honey. This method was used to examine seven varieties of honey: light, medium,
dark, blended, pasteurized, creamed, and meliponine. Plant and insect sources
were identified in five samples, but only the botanical or insect source could be
identified in the other two. Two samples were found to be misrepresented.
Although this method was generally successful in determining both plant and
insect sources, honeys rich in polyphenolic compounds or subject to
crystallization were recalcitrant to analysis, so further research is required to
combat honey adulteration and mislabeling.
PMID- 27507465
TI - A novel method for the synthesis of glyceryl monocaffeate by the enzymatic
transesterification and kinetic analysis.
AB - A novel enzymatic method for glyceryl monocaffeate (GMC) preparation by the
transesterification of ethyl caffeate (EC) was investigated. The effects of
reaction variables (reaction pressure, temperature, reaction time, enzyme load,
and substrate ratio) on the enzymatic transesterification were studied and
optimized using response surface methodology. HPLC-ESI-MS and HPLC-UV were used
to monitor the transesterification. Thermodynamics, kinetic analyses and reaction
mechanism were also evaluated. Results showed that, GMC can be successfully
prepared by the enzymatic transesterification of EC with glycerol. Under the
optimal conditions (enzyme load 22.54%, EC:glycerol=1:12.75 (mol/mol), 72.5
degrees C, and 10.5h), EC conversion and GMC yield were 97.9+/-0.7% and 95.8+/
1.0%, respectively. The activation energies (Ea) for EC conversion and GMC
formation were 44.23 and 46.51kJ/mol, respectively. The kinetic values for Vmax,
Km(') and KIA were 2.18*10(-3)mol/(Lmin), 0.086mol/L, and 0.52mol/L,
respectively. The transesterification mechanism with EC inhibition was also
proposed.
PMID- 27507466
TI - Changes in whole grain polyphenols and antioxidant activity of six sorghum
genotypes under different irrigation treatments.
AB - Sorghum grain containing elevated polyphenolic antioxidant content may provide
foods with benefits to human health. A study was undertaken to determine the
potential role of irrigation on the content of polyphenols and antioxidant levels
in sorghum grain. Bound, free and total polyphenols were investigated in six
diverse sorghum genotypes grown under either full irrigation or a deficit
irrigation regime. Results showed genotype, irrigation and their interaction had
a significant effect on polyphenols and antioxidant activity (P?0.05). The
deficit irrigation treatment significantly increased polyphenol content and
antioxidant activity compared to the full irrigation treatment. Of the six
genotypes Shawaya black short 1 and IS1311C (brown) showed the highest
polyphenols levels and antioxidant activity. Therefore, both irrigation
treatments and genotype need to be considered by sorghum breeders and farmers
during sorghum production to produce grain with the required levels of
polyphenolics and antioxidant activity for targeted end-use.
PMID- 27507467
TI - Enzymatic hydrolysis of phytate and effects on soluble oxalate concentration in
foods.
AB - Soluble oxalate in foods is major concern for kidney stone formers due to its
tendency to increase urinary oxalate concentration. Phytate forms complexes with
cations, which increases soluble oxalate by making cations unavailable to
precipitate oxalate. Thus, in order to reduce soluble oxalate, bran samples
(wheat, oat and barley) and bean samples (red kidney bean and white bean) were
treated with phytase. Release of phosphate after phytate degradation and its
association with calcium was determined. Phosphate concentration increased after
application of phytase in all samples, but effect on soluble oxalate
concentration varied. Wheat and oat bran showed significant reduction (P<0.05) in
soluble oxalate compared to bean samples. Wheat bran, oat bran and white bean had
a lower calcium:phosphate ratio than barley bran and red kidney beans.
Correlation of the calcium:phosphate molar ratio with release of phosphate
depends on concentration of calcium ions and this influences soluble oxalate
concentration.
PMID- 27507468
TI - Stabilization of starch-based microgel-lysozyme complexes using a layer-by-layer
assembly technique.
AB - The layer-by-layer assembly of polyelectrolyte multilayers of chitosan (CS) and
carboxymethyl starch (CMS) on soft and porous pH- and ionic strength-response
microgels was determined by confocal laser scanning microscopy (CLSM) and zeta
potential measurements. In vitro release of lysozyme from the stabilized
microgels under simulated gastric and intestinal fluids was also investigated.
The distribution of CS in the microgels was identified by CLSM, and the optimal
molecular weight of CS was 100kDa, which could only be absorbed on the microgel
surface. The CS was used as the first layer, while the CMS was used as the second
layer, and the zeta potential revealed that the optimal weight ratios of CS and
CMS to microgels in the complexes were 0.1 and 0.06, respectively. The in vitro
release experiments suggested that the stabilized double-layer microgel complexes
could potentially be applied as a carrier system to prevent early release in the
stomach to target intestinal delivery.
PMID- 27507469
TI - Coffee aroma: Chemometric comparison of the chemical information provided by
three different samplings combined with GC-MS to describe the sensory properties
in cup.
AB - This study is part of a wider project aiming to correlate the chemical
composition of the coffee volatile fraction to its sensory properties with the
end-goal of developing an instrumental analysis approach complementary to human
sensory profiling. The proposed investigation strategy compares the chemical
information concerning coffee aroma and flavor obtained with HS-SPME of the
ground coffee and in-solution SBSE/SPME sampling combined with GC-MS to evaluate
their compatibility with the cupping evaluation for quality control purposes.
Roasted coffee samples with specific sensory properties were analyzed. The
chemical results obtained by the three samplings were compared through
multivariate analysis, and related to the samples' sensory attributes. Despite
the differences between the three sampling approaches, data processing showed
that the three methods provide the same kind of chemical information useful for
sample discrimination, and that they could be used interchangeably to sample the
coffee aroma and flavor.
PMID- 27507470
TI - Comparison of phytochemical profiles and health benefits in fiber and oil
flaxseeds (Linum usitatissimum L.).
AB - Flaxseed (Linum usitatissimum L.) is a rich source of nutritive and bioactive
compounds. The research evaluated the disparity in phytochemical profiles along
with total and cellular antioxidant activities between oil and fiber flaxseeds.
There were significant differences in total phenolics, total flavonoids and
antioxidant activities among the six cultivars of fiber and oil flaxseed,
respectively. Four phytochemical compounds including caffeic acid, p-coumaric
acid and ferulic acid, and secoisolariciresinol diglucoside (SDG) were identified
and quantified in the cultivars of oil and fiber flaxseed by HPLC analysis.
Notably, the average of total phenolic and flavonoid contents, along with total
antioxidant activities between fiber and oil flaxseeds were not different
significantly; even the cellular antioxidant activity of fiber flaxseed was
superior to oil flaxseed. These results suggest that fiber flaxseeds would be
valuable candidates as functional products and dietary supplements production
owing to the higher bioactive values as well as oil flaxseeds.
PMID- 27507471
TI - Anthocyanins degradation during storage of Hibiscus sabdariffa extract and
evolution of its degradation products.
AB - Degradation parameters of two main anthocyanins from roselle extract (Hibiscus
sabdariffa L.) stored at different temperatures (4-37 degrees C) over 60days were
determined. Anthocyanins and some of their degradation products were monitored
and quantified using HPLC-MS and DAD. Degradation of anthocyanins followed first
order kinetics and reaction rate constants (k values), which were obtained by non
linear regression, showed that the degradation rate of delphinidin 3-O
sambubioside was higher than that of cyanidin 3-O-sambubioside with k values of
9.2.10(-7)s(-1) and 8.4.10(-7)s(-1) at 37 degrees C respectively. The temperature
dependence of the rate of anthocyanin degradation was modeled by the Arrhenius
equation. Degradation of delphinidin 3-O-sambubioside (Ea=90kJmol(-1)) tended to
be significantly more sensitive to an increase in temperature than cyanidin 3-O
sambubioside (Ea=80kJmol(-1)). Degradation of these anthocyanins formed scission
products (gallic and protocatechuic acids respectively) and was accompanied by an
increase in polymeric color index.
PMID- 27507472
TI - A method for producing superfine black tea powder with enhanced infusion and
dispersion property.
AB - Tea is rich in healthy components including polyphenols, caffeine, gallic acids,
and others. Current technology of tea infusion and extraction leads to more than
40% soluble solids wasted in spent leaf. To increase the bioaccessibility of
black tea, we report a method of pulverization treatments including general and
superfine grinding to reduce the particle size. In comparison with coarsely
ground black tea powders (BTPs), the superfine ground BTP with medium diameter
6.9MUm resulted in significant higher infusion yield of total polyphenols (TPP),
caffeine, and water-soluble carbohydrate (WSC). The total water-soluble solids
(WSS) of superfine BTP infusion increased markedly by twice due to the
accelerated diffusion and enhanced solubility. High correlation between particle
size and sedimentation ratio suggested improved dispersion stability of superfine
BTP. The optimal dispersion of 0.1% superfine BTP in water was obtained by
combination of homogenization and 0.08% CMC-Na formulation with 27.05%
centrifugal sedimentation ratio.
PMID- 27507473
TI - Seed coat color and seed weight contribute differential responses of targeted
metabolites in soybean seeds.
AB - The distribution and variation of targeted metabolites in soybean seeds are
affected by genetic and environmental factors. In this study, we used 192 soybean
germplasm accessions collected from two provinces of Korea to elucidate the
effects of seed coat color and seeds dry weight on the metabolic variation and
responses of targeted metabolites. The effects of seed coat color and seeds dry
weight were present in sucrose, total oligosaccharides, total carbohydrates and
all measured fatty acids. The targeted metabolites were clustered within three
groups. These metabolites were not only differently related to seeds dry weight,
but also responded differentially to seed coat color. The inter-relationship
between the targeted metabolites was highly present in the result of correlation
analysis. Overall, results revealed that the targeted metabolites were diverged
in relation to seed coat color and seeds dry weight within locally collected
soybean seed germplasm accessions.
PMID- 27507474
TI - Comparison of alpha-amylase, alpha-glucosidase and lipase inhibitory activity of
the phenolic substances in two black legumes of different genera.
AB - Antioxidant-rich plant foods can inhibit starch and lipid digestions that are
relevant to diabetes management. Two high-antioxidant black legumes, black
soybean (Glycine max) and black turtle bean (Phaseolus vulgaris), belonging to
two different genera were used to investigate their capacity against digestive
enzymes. Phenolic substances were compared in crude, semi-purified extracts (semi
purified by XAD-7 column), and fractions (fractionationed by Sephadex LH-20
column) from these two legumes. In addition, their antioxidant capacities and
abilities to inhibit digestive enzymes were characterized. Results showed that
Fraction V from black soybean was the most effective (IC50: 0.25mg/mL) against
alpha-amylase; Fraction V from black turtle bean was the most potent (IC50:
0.25MUg/mL) against alpha-glucosidase; Fraction IV from black turtle bean was the
most powerful (IC50: 76MUg/mL) against lipase. Of the pure phenolic compounds
tested, myricetin showed the highest inhibition of alpha-amylase, alpha
glucosidase and lipase (IC50: 0.38mg/mL, 0.87MUg/mL and 15MUg/mL, respectively).
PMID- 27507475
TI - Oxyresveratrol and ascorbic acid O/W microemulsion: Preparation,
characterization, anti-isomerization and potential application as antibrowning
agent on fresh-cut lotus root slices.
AB - The purpose of this study is to prepare an oxyresveratrol (Oxy) microemulsion
(ME) with improved Oxy's solubility and stability and to investigate its
antibrowning effects on fresh-cut lotus root slices. The formula of OxyME
consisted of ethyl butyrate, Tween 80, PEG400, and water with w/w of 4%, 10.67%,
5.33%, and 80%, respectively. Encapsulating Oxy into OxyME greatly increased its
solubility and stability compared with that of in water. Strong antibrowning
effects were observed on fresh-cut lotus root slices treated with OxyME, even
better than 4-hexylresorcinol. The addition of ascorbic acid (VC) into OxyME
greatly improved the Oxy stability in long-term storage and antibrowning effects
on fresh-cut lotus root slices. However, the simultaneous addition of calcium
chloride and VC did not obviously improve the antibrowning effects compared with
the addition of VC alone. These results indicated that Oxy+VCME may be suitable
as an antibrowning agent for fresh-cut vegetables.
PMID- 27507476
TI - Effect of polyglycerol esters additive on palm oil crystallization using focused
beam reflectance measurement and differential scanning calorimetry.
AB - The effect of 0.1-0.7% (w/w) of polyglycerol esters (PGEmix-8) on palm oil
crystallization was studied using focused beam reflectance measurement (FBRM) to
analyze the in-line changes of crystal size distribution during the
crystallization. FBRM results show that 0.1-0.5% (w/w) of PGEmix-8 did not
significantly affect nucleation but slightly retarded crystal growth. The use of
0.7% (w/w) additive showed greater heterogeneous nucleation compared to those
with lower dosages of additive. Crystal growth was also greatly reduced when
using 0.7% (w/w) dosage. The morphological study indicated that the palm oil
crystals were smaller and more even in size than when more additive was added.
Isothermal crystallization studies using differential scanning calorimetry (DSC)
showed increased inhibitory effects on palm oil crystal growth with increasing
concentration of PGEmix-8. These results imply that PGEmix-8 is a nucleation
enhancing and crystal growth retarding additive in palm oil crystallization at
0.7% (w/w) dosage.
PMID- 27507477
TI - Effect of parboiling on phytochemical content, antioxidant activity and
physicochemical properties of germinated red rice.
AB - In order to improve functional properties and palatability of germinated red
rice, this study investigated differences in phytochemicals and physicochemical
properties of germinated red rice at 2, 5, 10, 15min of parboiling. Total free
phenolic content and antioxidant activity of germinated red rice parboiled for 5
and 15min was higher than that of germinated red rice. Free p-coumaric acid
increased from 0.20 to 0.67mg/100g with parboiling time increasing from 5 to
15min. Bound vanillic (0.17-0.27mg/100g) and p-coumaric acid (6.56-8.59mg/100g)
had higher levels at 0, 2, or 5min. During 15min of parboiling, color difference
(DeltaE) increased from 0.58 to 9.09, heat enthalpy (DeltaH) decreased from 4.69
to 1.94J/g, and internal structure of rice was destroyed. Overall, parboiling
time of less than 5min was suitable to improve the quality of germinated red
rice.
PMID- 27507478
TI - Phenolic compound in beans as protection against mycotoxins.
AB - Phenolic compounds, their inhibitory activity against fungal amylase and the
occurrence of aflatoxins were determined in edible beans. The free, conjugated
and bounded phenolic compounds and their phenolic acid profiles were determined
in ten bean varieties. A method for aflatoxin B1, B2, G1 and G2 determination and
confirmation by LC-MS/MS was validated. The red and carioca beans presented the
highest total phenolic content (1.8 and 1.2mg.g(-1), respectively); the fradinho
and white beans the lowest (0.18 and 0.19mg.g(-1), respectively). In the free and
conjugated forms, chlorogenic acid was present in 60% of the samples, while in
the bounded phenolic, ferulic acid was in 90% of the samples. The phenolic
extracts were able to inhibit fungal amylase, and the PCA analysis confirmed that
the relation between the chlorogenic and gallic acids is important to this
effect. The absence of aflatoxins in samples confirm the protector effects of
these phenolic compounds.
PMID- 27507479
TI - Capillary electrophoresis method with UV-detection for analysis of free amino
acids concentrations in food.
AB - Simple and inexpensive capillary electrophoresis with UV-detection method (CE-UV)
was optimized and validated for determination of six amino acids namely (alanine,
asparagine, glutamine, proline, serine and valine) for Sudanese food. Amino acids
in the samples were derivatized with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD
Cl) prior to CE-UV analysis. Labeling reaction conditions (100mM borate buffer at
pH 8.5, labeling reaction time 60min, temperature 70 degrees C and NBD-Cl
concentration 40mM) were systematically investigated. The optimal conditions for
the separation were 100mM borate buffer at pH 9.7 and detected at 475nm. The
method was validated in terms of linearity, limit of detection (LOD), limit of
quantification (LOQ), precision (repeatability) (RSD%) and accuracy (recovery).
Good linearity was achieved for all amino acids (r(2)>0.9981) in the
concentration range of 2.5-40mg/L. The LODs in the range of 0.32-0.56mg/L were
obtained. Recoveries of amino acids ranging from 85% to 108%, (n=3) were
obtained. The validated method was successfully applied for the determination of
amino acids for Sudanese food samples.
PMID- 27507480
TI - Storage stability of phenolic compounds in powdered BRS Violeta grape juice
microencapsulated with protein and maltodextrin blends.
AB - The stabilities of the phenolic compounds, antioxidant activity and colour
parameters of microencapsulated powdered BRS Violeta red grape juice were
evaluated throughout storage at 5, 25 and 35 degrees C for up to 150days.
Different soy protein (S) or whey protein (W) blends with maltodextrin (M) were
used as carrier agents, added at diverse concentrations and proportions. The
treatment combining S and M with the highest carrier agent concentration (1SM)
preserved almost all the anthocyanins. Except for 1SM, the proportion of p
coumaroylated anthocyanins increased during storage, and the flavonol content of
the 1SM powder decreased after 150days. The hydroxycinnamate content decreased
for all treatments, independent of storage temperature, and flavan-3-ols were
lost at 35 degrees C. The time and temperature did not influence the antioxidant
activity of the powder or the colour of the reconstituted grape juice after
150days.
PMID- 27507481
TI - Effects of salts on the gelatinization and retrogradation properties of maize
starch and waxy maize starch.
AB - The objective of this study was to evaluate the effects of salts on the
gelatinization and retrogradation of maize and waxy maize starch. Experimental
results showed that the salting-out or structure-making ions, such as F(-) and
SO4(2-), decreased the swelling power, solubility and transparency of both
starches, but increased the gelatinization temperature, enthalpy, and syneresis,
due to the tendency of these ions to protect the hydrogen bond links among starch
molecules. On the other hand, the salting-in or structure-breaking ions, such as
I(-) and SCN(-), exhibited the opposite effects. Microscopic observations
confirmed such effects of salts on both starches. Furthermore, the effects of
salts were more significant on waxy maize and on normal maize starch. Generally,
salts could significantly influence on the gelatinization and retrogradation of
maize and waxy maize starch, following the order of the Hofmeister series.
PMID- 27507482
TI - Study on the metabolites of isoalantolactone in vivo and in vitro by ultra
performance liquid chromatography combined with Triple TOF mass spectrometry.
AB - Isoalantolactone (IAL) is an active sesquiterpene naturally present in many
vegetables, condiments and medicinal plants. In this study, an efficient strategy
was developed for the identification of metabolites following the in vivo
metabolism and in vitro biotransformation of IAL with rat intestinal bacteria
utilizing ultra performance liquid chromatography combined with Triple TOF mass
spectrometry (UPLC-Triple TOF-MS/MS). As a result, 46 metabolites including 34
novel sulfur-containing products were identified. The results demonstrated that
IAL could undergo general metabolic reactions, including oxidation, hydration,
hydrogenation, demethylation, cysteine conjugation and N-acetylcysteine
conjugation, but the most noticeable characteristic of IAL metabolism was the H2S
addition to the double bond between C-11 and C-13 and subsequent reactions to
produce a series of novel sulfur-containing dimers. This is the first study of
IAL metabolism in vivo, whose results provide novel and useful data for a better
understanding of the safety and efficacy of IAL.
PMID- 27507483
TI - Optimisation of selective alkaline extraction for Cr(VI) determination in dairy
and cereal products by HPIC-ICPMS using an experimental design.
AB - This study presents the optimisation through an experimental design then the
validation of a method to determine Cr(VI) in certain foodstuffs by high
performance ionic chromatography with inductively coupled plasma mass
spectrometry. This method is free from interferences possibly associated with
chloride and organic or inorganic carbon. Analytical performances assessed by the
accuracy profile method were satisfactory in terms of linearity, specificity,
sensitivity, accuracy, repeatability and intermediate precision. Limits of
quantification ranged from 0.6MUg.kg(-1) in dairy products to 0.8MUg.kg(-1) in
cereal products. The method was applied to the determination of Cr(VI) in dairy
and cereal products from different brands and origins. Despite the method's very
high sensitivity, Cr(VI) was not found in all the studied samples. This confirms
the results of the most recent studies using an on-line speciation method, and
invalidates older studies that found traces of Cr(VI) in food by using a less
specific off-line speciation method.
PMID- 27507484
TI - Characterization of a salt-tolerant aminopeptidase from marine Bacillus
licheniformis SWJS33 that improves hydrolysis and debittering efficiency for soy
protein isolate.
AB - An aminopeptidase was isolated from the marine Bacillus licheniformis SWJS33
(BLAP) and purified. According to the tandem mass spectrometry, the enzyme
displayed 11% amino acid identity with the aminopeptidase from Bacillus
(gi|496687392). BLAP exhibited maximum activity at 60 degrees C and pH 8.0-8.5
and had a molecular mass of 100kDa. The presence of NaCl enabled 50% improvement
of enzyme activity with 10-15% NaCl being the best. The observed inactivation by
EDTA and bestatin and activation by Co(2+) and Ag(+) indicated that the obtained
enzyme was a metalloaminopeptidase. Such an aminopeptidase could further improve
the hydrolysis degree of soy protein isolate hydrolysates catalyzed by papain,
Alcalase 2.4L or Flavourzyme 500MG from 8.5%, 9.5% or 14.4-18.8%, 18.7% or 20.1%,
respectively, while decreasing the bitter intensity score of the SPI hydrolysates
catalyzed by Alcalase 2.4L from 3.6 to 0.4.
PMID- 27507485
TI - Direct activation of GABAA receptors by substances in the organic acid fraction
of Japanese sake.
AB - We investigated the effect of substances present in Japanese sake on the response
of ionotropic gamma-aminobutyric acid (GABA)A receptors expressed in Xenopus
oocytes. Sake was fractionated by ion-exchange chromatography. The fraction
containing organic acids (OA fraction) showed agonist activities on the GABAA
receptor. OA fractions from sake were analyzed by capillary electrophoresis time
of-flight mass spectrometry (CE-TOFMS). Of the 64 compounds identified, 13
compounds showed GABAA receptor agonist activities. Especially, l-lactic acid
showed high agonist activity and its EC50 value was 37MUM. Intraperitoneal
injections of l-lactic acid, gluconic acid, and pyruvic acid (10, 10, and 5mg/kg
BW, respectively), which showed agonistic activity on the GABAA receptor, led to
significant anxiolytic effects during an elevated plus-maze test in mice.
PMID- 27507486
TI - Methylmercury varies more than one order of magnitude in commercial European
rice.
AB - Rice is known to accumulate methylmercury (MeHg) in the rice grains. MeHg as a
neurotoxin impacts on the human central nervous systems and especially on the
developing brain. In this exploratory study, 87 commercial rice products sold in
Europe, including nine baby-rice products, were analyzed for total Hg and MeHg
content. MeHg concentration in all rice products investigated range from 0.11 to
6.45MUgkg(-1) with an average value of 1.91+/-1.07MUgkg(-1) and baby-rice is not
significantly different from other rice products. Total Hg ranges from 0.53 to
11.1MUgkg(-1) with an average of 3.04+/-2.07MUgkg(-1). MeHg concentrations in all
rice products studied in this work would not exceed the provisional tolerable
weekly intake (PTWI). 30% of all commercial market rice products exceeded 10% of
the PTWI calculated for toddlers or 13% of products for adults with rice based
diet.
PMID- 27507487
TI - Facile preparation of water soluble curcuminoids extracted from turmeric (Curcuma
longa L.) powder by using steviol glucosides.
AB - Curcuminoids from rhizomes of Curcuma longa possess various biological
activities. However, low aqueous solubility and consequent poor bioavailability
of curcuminoids are major limitations to their use. In this study, curcuminoids
extracted from turmeric powder using stevioside (Ste), rebaudioside A (RebA), or
steviol glucosides (SG) were solubilized in water. The optimum extraction
condition by Ste, RebA, or SG resulted in 11.3, 9.7, or 6.7mg/ml water soluble
curcuminoids. Curcuminoids solubilized in water showed 80% stability at pH from
6.0 to 10.0 after 1week of storage at 25 degrees C. The particle sizes of
curcuminoids prepared with Ste, RebA, and SG were 110.8, 95.7, and 32.7nm,
respectively. The water soluble turmeric extracts prepared with Ste, RebA, and SG
showed the 2,2-diphenyl-1-picrylhydrazyl radical scavenging (SC50) activities of
127.6, 105.4, and 109.8MUg/ml, and the inhibition activities (IC50) against NS2B
NS3(pro) from dengue virus type IV of 14.1, 24.0 and 15.3MUg/ml, respectively.
PMID- 27507489
TI - DNA barcoding for identification of consumer-relevant mushrooms: A partial
solution for product certification?
AB - One challenge in the dietary supplement industry is confirmation of species
identity for processed raw materials, i.e. those modified by milling, drying, or
extraction, which move through a multilevel supply chain before reaching the
finished product. This is particularly difficult for samples containing fungal
mycelia, where processing removes morphological characteristics, such that they
do not present sufficient variation to differentiate species by traditional
techniques. To address this issue, we have demonstrated the utility of DNA
barcoding to verify the taxonomic identity of fungi found commonly in the food
and dietary supplement industry; such data are critical for protecting consumer
health, by assuring both safety and quality. By using DNA barcoding of nuclear
ribosomal internal transcribed spacer (ITS) of the rRNA gene with fungal specific
ITS primers, ITS barcodes were generated for 33 representative fungal samples,
all of which could be used by consumers for food and/or dietary supplement
purposes. In the majority of cases, we were able to sequence the ITS region from
powdered mycelium samples, grocery store mushrooms, and capsules from commercial
dietary supplements. After generating ITS barcodes utilizing standard procedures
accepted by the Consortium for the Barcode of Life, we tested their utility by
performing a BLAST search against authenticate published ITS sequences in
GenBank. In some cases, we also downloaded published, homologous sequences of the
ITS region of fungi inspected in this study and examined the phylogenetic
relationships of barcoded fungal species in light of modern taxonomic and
phylogenetic studies. We anticipate that these data will motivate discussions on
DNA barcoding based species identification as applied to the
verification/certification of mushroom-containing dietary supplements.
PMID- 27507488
TI - Selenium-enriched durum wheat improves the nutritional profile of pasta without
altering its organoleptic properties.
AB - Two field experiments were conducted over three growing seasons (2006-07, 2008-09
and 2009-10) to evaluate Se-enriched pasta through foliar fertilization at
various rates and timing of application on 4 durum wheat varieties. Our findings
confirm the effectiveness of foliar Se fertilization to increase Se
concentrations in durum wheat grain, even at high Se rates (120gSeha(-1)). Se
fortification was significant across different genotypes, with greater Se
accumulation in landraces ('Timilia') and obsolete varieties ('Cappelli'), with
respect to modern varieties. The Se content in the grain was increased by up to
35-fold that of the untreated control. The Se concentration decreased during
milling (11%), while processing and cooking of pasta did not show significant
decreases. This biofortification stategy had no effects on grain quality
parameters, except for reduced gluten index in the high-gluten variety PR22D89,
as well as for the sensorial properties of the spaghetti.
PMID- 27507490
TI - Changes in chemical interactions and protein conformation during heat-induced
wheat gluten gel formation.
AB - In order to elucidate the heat-induced wheat gluten gel formation mechanism,
changes in chemical interactions and protein conformation were investigated
during gelation. The contribution of ionic and hydrogen bonds were found to
decrease from 0.746 and 4.133g/L to 0.397 and 2.733g/L, respectively, as the
temperature increased from 25 to 90 degrees C. Moreover, the free SH content
remarkably decreased from 37.91 to 19.79MUmol/g during gelation. Ultraviolet
absorption spectra and intrinsic fluorescence spectra suggested that wheat gluten
unfolded during the heating process. In addition, wheat gluten gels treated at 80
and 90 degrees C exhibited a "steric hindrance" effect, which can be attributed
to the formation of aggregates. Fourier transform infrared spectra suggested that
the random coil content increased at low temperatures (40 and 50 degrees C),
whereas the content of intermolecular beta-sheets due to protein aggregation
increased from 38.10% to 44.28% when the gelation temperature was 90 degrees C.
PMID- 27507491
TI - Mineral content of sorghum genotypes and the influence of water stress.
AB - Sorghum is a source of several minerals whose content may vary depending on the
genotype and the production environment. The objective of this study was to
screen sorghum genotypes for mineral content and to investigate the effect of
water stress on it. A large variability was observed in the mineral content of
100 sorghum genotypes grown in environments without (WoWS) and with water stress
(WthWS). The water stress decreased Mn, P, Mg and S contents in 100, 96, 93 and
56% of genotypes, respectively. The genotypes and other factors seemed to have
more impact than water stress on K, Ca, Cu, Fe and Zn levels. In 100 sorghum
genotypes, 2 were classified as excellent sources of Fe and 25 of Zn, in both
environments. The best two genotypes to Fe content were SC21 and SC655 and to Zn
were SC320 and SHAN-QUI-RED which showed great potential for use in
biofortification.
PMID- 27507492
TI - Transcriptional regulation of lycopene metabolism mediated by rootstock during
the ripening of grafted watermelons.
AB - Rootstocks have comprehensive effects on lycopene accumulation in grafted
watermelon fruits. However, little is known about lycopene metabolic regulation
in grafted watermelon. To address this problem, parallel changes in lycopene
contents and the expression of its metabolic genes were analyzed during the fruit
ripening of nongrafted watermelon and watermelon grafted onto bottle gourd,
pumpkin, and wild watermelon. Results showed that rootstocks mediated the
transcriptional regulations of lycopene accumulation in different ways. Bottle
gourd and wild watermelon promoted lycopene accumulation in grafted watermelon
fruits by upregulating the biosynthetic genes phytoene synthase (PSY) and zeta
carotene desaturase (ZDS), and downregulating the catabolic genes beta-carotene
hydroxylase (CHYB), zeaxanthin epoxidase (ZEP), 9-cis-epoxycarotenoid dioxygenase
(NCED), and carotenoid cleavage dioxygenase (CCD). However, pumpkin did not
affect lycopene accumulation by upregulating both biosynthetic and catabolic
genes. The rootstock-dependent characteristic of lycopene accumulation in grafted
watermelon fruits provided an alternative model for investigating lycopene
metabolic regulation.
PMID- 27507493
TI - Hydrothermal changes in wheat starch monitored by two-dimensional NMR.
AB - The temperature-dependent changes in wheat starch powder and wheat starch-water
mixtures were monitored in real-time throughout the heating/cooling program using
a classical one-dimensional T1 method and a novel bi-dimensional approach to
correlate spin-lattice and spin-spin relaxation times (T1-T2) including
acquisition of the FID signal. The influence of two controlling factors (i.e.
water content (11%, 35-50%, wet basis) and temperature (20-90 degrees C and back
to 20 degrees C)) on water distribution and starch transformation was
investigated. Quantitative analysis of 2D T1-T2 maps greatly facilitated the
interpretation of T1 relaxation times, which have been interpreted rather
narrowly in the literature when classically measured in one-dimension.
Application of the new IR-FID-CPMG sequence allowed distinction between different
proton pools with different T1 relaxation times, particularly when the starch
gelatinization occurred. The quantification of each T1 component permitted to
assign the short T1 to slow cross relaxation phenomena, highlighting proton
chemical and/or diffusional exchanges between water and starch.
PMID- 27507494
TI - Aggregation and conformational change of mushroom (Agaricus bisporus)
polyphenoloxidase subjected to thermal treatment.
AB - This study investigated changes in the activity, conformation and microstructure
of mushroom polyphenoloxidase (PPO) subjected to thermal treatment. The
inactivation of PPO can be achieved by high temperature-short time or mild
temperature-long time treatment. Circular dichroism and fluorescence spectra
suggested that heating process induced the rearrangement of secondary structure
and the disruption of tertiary structure. Red shifts of fluorescence spectra
showed positive correlations with the inactivation rate of PPO. There were
significant differences in the conformation and molecular microstructure among
PPO samples with the same relative activity, which were obtained by treating PPO
at 45, 55 and 65 degrees C for different times. In summary, PPO molecules were
deformed at mild temperature, while higher temperature induced the formation of
large aggregates. PPO with the same relative activity might exist in different
forms.
PMID- 27507495
TI - Effects of clove essential oil and eugenol on quality and browning control of
fresh-cut lettuce.
AB - This study confirmed the inhibitory effects of clove essential oil (CEO) and
eugenol (EUG) on the browning and relevant enzymes of fresh-cut lettuce, and
examined associated mechanisms by inhibition kinetics and computational docking
analysis. Fresh-cut lettuce was treated with 0.05% CEO and 0.05% EUG solutions,
resulting in inhibition of the deterioration of texture quality and browning of
the lettuce surface and interior. Compared with the controls, CEO and EUG
significantly inhibited the activities of phenylalanine ammonia lyase (PAL),
polyphenol oxidase (PPO), and peroxidase (POD, all p<0.05). EUG suppressed PAL,
PPO, and POD in vitro in a dose-dependent manner, with IC50 values of 5.4+/-0.9,
29.5+/-3.5, and 61.9+/-6.7mM, respectively. The binding and inhibition effects of
EUG on PAL, PPO, and POD, determined by inhibition kinetics and computational
docking analysis, established EUG as a competitive inhibitor of these browning
relevant enzymes.
PMID- 27507496
TI - Multi-mycotoxin contamination of couscous semolina commercialized in Morocco.
AB - The multi-mycotoxin contamination of ninety-eight (98) couscous semolina samples
collected from various areas in Morocco was investigated in this study. Samples
were surveyed for the presence of 22 mycotoxins (four aflatoxins, ochratoxin A,
diacetoxiscyrpenol (DAS), three fumonisins, beauvericin (BEA), deoxynivalenol
(DON), 15-acetyl-deoxynivalenol (15-ADON), 3-acetyl-deoxynivalenol (3-ADON),
nivalenol (NIV), sterigmatocystin (STG), zearalenone (ZEA), four enniatins, T-2
and HT-2 toxins). Results showed that 96 out of 98 total couscous samples (98%)
were contaminated by at least one mycotoxin. Enniatin B (ENB), Enniatin B1
(ENB1), Enniatin A1 (ENA1) and zearalenone (ZEA) have shown the highest
incidences in contaminated samples. The dietary exposure was estimated to be
1.02, 0.57, 0.06, 0.57 and 0.3MUg/kgbw/day for the sum of (DON+3-ADON+15-ADON),
fumonisins (FB1+FB2+FB3), the sum of (T2+HT-2), NIV and ZEA, respectively.
PMID- 27507497
TI - Contribution of trans-aconitic acid to DPPH scavenging ability in different
media.
AB - The antioxidant properties of trans-aconitic acid (TAA) alone or in the presence
of usual antioxidants were assessed by DPPH assay. The IC50 value equal to 70mM
was very high compared to usual antioxidants (vitamin C and trolox). A joint
experimental/theoretical study suggested that hydrogen atom abstraction in TAA by
DPPH was located on -CH2- methylene bridge because the corresponding radical was
more stabilized than COO(.) and CC(.) radicals. In combination with antioxidants
(vitamin C, gallic acid, caffeic acid, trolox), synergy or additivity effects
were noticed. The magnitude of the synergistic effect varied between 1.06 and
1.24 depending on the type and concentration of antioxidant for a concentration
of TAA equal to 22.3mM. Especially, the addition of TAA at a concentration below
32mM to a solution containing 20MUM of vitamin C had a synergy effect. Beyond
this concentration, TAA showed an additive effect.
PMID- 27507498
TI - The whole grain content of foods consumed in the UK.
AB - This study aimed to assess the whole grain (WG) content of foods consumed in the
UK which include ingredients that retain all three structural components of the
grain, and contained ?10% WG. Dietary data from seven studies with 10,474 UK
subjects were examined for foods containing WG. The WG content was then
determined from ingredient lists, manufacturers' information and recipes. 372
food descriptors from nine food groups (4.4% of all food codes) contained ?10%
WG. Of these 372 foods, 31.5% contained ?51%, 30.6% 25-50%, and 37.9% 10-24% WG
dry matter as eaten. The relatively small number of WG foods identified in the
total number of foods consumed confirms the low contribution of WG foods to the
overall pattern of foods consumed in the UK. Since foods containing <51% WG
accounted for the majority of WG food codes identified, recognising the
importance of these foods to WG intake is essential.
PMID- 27507499
TI - Black bean (Phaseolus vulgaris L.) protein hydrolysates: Physicochemical and
functional properties.
AB - Black bean protein hydrolysates obtained from pepsin and alcalase digestions
until 120min of hydrolysis were evaluated by gel electrophoresis, relative
fluorescence intensity, emulsifying properties, light micrograph of emulsions and
in vitro antioxidant activity. The emulsion stability of the bean protein
hydrolysates were evaluated during 30days of storage. The pepsin-treated bean
protein hydrolysates presented higher degree of hydrolysis than the alcalase
treated protein hydrolysates. The alcalase-treated bean protein hydrolysates
showed higher surface hydrophobicity. Moreover, the protein hydrolysates obtained
with alcalase digestion presented higher emulsion stability during 30-days than
those obtained from pepsin digestion. The protein concentrate and especially the
hydrolysates obtained from alcalase digestion had good emulsion stability and
antioxidant activity. Thus, they could be exploited as protein supplements in the
diet as nutritional and bioactive foods.
PMID- 27507500
TI - Fatty acids and fat-soluble vitamins in ewe's milk predicted by near infrared
reflectance spectroscopy. Determination of seasonality.
AB - The aim of the present work was to determine the fatty acid and fat-soluble
vitamin composition and the season of ewe's milk production using NIR
spectroscopy. 219 ewe's milk samples from different breeds and feeding regimes
were taken each month over one year. Fatty acids were analyzed by gas
chromatography, and retinol and alpha-, and gamma-tocopherol by liquid
chromatography. The results showed that the quantification was more accurate for
the milk dried on paper, except for vitamins. Calibration statistical descriptors
on milk dried on paper were good for capric, lauric, myristic, palmitoleic,
stearic and oleic acids, and acceptable for caprilic, undecanoic, 9c, 11tCLA,
SigmaCLA, PUFA, omega3, omega6, retinol and alpha-tocopherol. The equations for
the discrimination of seasonality was obtained using the partial least squares
discriminant analysis (PLSDA) algorithm. 93% of winter samples and 89% of summer
samples were correctly classified using the NIR spectra of milk dried on paper.
PMID- 27507501
TI - Evaluation studies of persimmon plant (Diospyros kaki) for physiological benefits
and bioaccessibility of antioxidants by in vitro simulated gastrointestinal
digestion.
AB - This study aims to analyze the antioxidant benefits from persimmon leaf tea,
fruit and fibres taking into account their changes along gastrointestinal
digestion. The evolution of polyphenols, flavonoids and antioxidant capacity was
studied using the recent harmonized in vitro protocol published by Minekus et al.
(2014). The digestion was performed with and without digestive enzymes. Results
showed aqueous leaf extract was richer in antioxidants than the fruit or the
extracted fibres. Nevertheless, persimmon-leaf antioxidants were more sensitive
to the digestive environment. In general, the oral conditions greatly affected
the antioxidants, while gastric digestion led to slight additional losses. The
intestinal step enhanced polyphenols and flavonoids solubility coming from the
fruit and fibres. Additionally, the presence of digestive enzymes positively
contributed to antioxidant release throughout digestion. Finally, the
bioaccessibility of polyphenols, flavonoids and antioxidant activity of persimmon
fruit were 1.4, 1.0 and 3.8 times higher than in aqueous leaf extract.
PMID- 27507502
TI - The food matrix affects the anthocyanin profile of fortified egg and dairy
matrices during processing and in vitro digestion.
AB - The aim of the present study was to understand to what extent the inclusion of
anthocyanins into dairy and egg matrices could affect their stability after
processing and their release and solubility during digestion. For this purpose,
individual and total anthocyanin content of four different enriched matrices,
namely custard dessert, milkshake, pancake and omelettete, was determined after
their manufacturing and during in vitro digestion. Results showed that
anthocyanin recovery after processing largely varied among matrices, mainly due
to the treatments applied and the interactions developed with other food
components. In terms of digestion, the present study showed that the inclusion of
anthocyanins into food matrices could be an effective way to protect them against
intestinal degradation, and also the incorporation of anthocyanins into matrices
with different compositions and structures could represent an interesting and
effective method to control the delivery of anthocyanins within the different
compartments of the digestive tract.
PMID- 27507503
TI - Crystallization kinetics of cocoa butter in the presence of sorbitan esters.
AB - Cocoa butter crystallization in the presence of sorbitan mono- and triesters or
canola oil was investigated. Solid-state surfactant esters accelerated early
stage cocoa butter solidification while suppressing later growth. Sorbitan
tristearate showed the strongest effect, followed by sorbitan monostearate and
sorbitan monopalmitate. Liquid-state surfactants suppressed cocoa butter
crystallization at all time points, with sorbitan trioleate showing a stronger
effect than sorbitan monooleate, which behaved in a similar fashion to canola
oil. Via DSC, the palmitic and stearic-based surfactants only associated with
cocoa butter's high-melting fraction, with the oleic acid-based surfactants and
canola oil showing little influence. All sorbitan esters had little effect on
polymorphism, whereas canola oil accelerated the form II-to-III-to-IV transition.
The palmitic and stearic-based surfactants greatly reduced cocoa butter crystal
size whereas the oleic acid-based surfactants and canola showed no notable
effect. Overall, sorbitan esters impacted cocoa butter crystallization kinetics,
though this depended on surfactant structure and concentration.
PMID- 27507504
TI - Secondary structure and conformational change of mushroom polyphenol oxidase
during thermosonication treatment by using FTIR spectroscopy.
AB - To understand the conformational changes of mushroom PPO, the secondary
structural change of the enzyme during thermosonication treatment at different
power (60, 80 and 100%), temperature (20-60 degrees C) and time (0-30min)
combinations was investigated by using FTIR spectroscopy and compared with the
change in enzyme activity. The enzyme inactivation higher than 99% was obtained
at 100% amplitude at 60 degrees C for 10min. FTIR studies showed that marked
spectral changes were noted after ultrasound treatment at 20 degrees C. The alpha
helix and beta-sheet contents decreased, while aggregated beta-sheet, turns and
random coil contents increased as temperature increased up to 60 degrees C during
thermosonication treatment for 10min indicating protein denaturation. Aggregated
bands located at 1683 and 1616cm(-1) became evident after ultrasound treatment at
40 degrees C. When temperature was lowered back to 25 degrees C, from ultrasound
treatment at 60 degrees C, these bands were still observed, indicating the
irreversible change in the structure.
PMID- 27507505
TI - High-throughput assay comparison and standardization for metal chelating capacity
screening: A proposal and application.
AB - Aiming to standardize the experimental protocols to assess the ability to chelate
Fe(2+) and Cu(2+) using 96-well microplates, we analyzed Brazilian coffees (n=20)
as a study-case in relation to their antioxidant activity using conventional
methods (DPPH and FRAP assays) and correlated the results with the total phenolic
content (TPC) using bivariate and multivariate statistical approaches.
Complementarily, we assessed the repeatability, reproducibility, recovery, and
linearity of both methods. Data showed that the proposed assays presented a good
repeatability and reproducibility (<7% RSD) and mean recovery values of 96.66%
and 98.91% for the iron and copper assays, respectively. Both methods were linear
in the range of 0-100mg EDTA equivalents/L. Cu(2+)-chelating ability was
significantly correlated to FRAP, DPPH, and TPC, while sparse (p<0.05)
correlations were obtained with Fe(2+)-chelating ability. Overall, both micro
assays can be used to assess the ability of plant-based extracts to chelate
Fe(2+) and Cu(2+)in vitro.
PMID- 27507506
TI - Determination of oligomeric proanthocyanidins and their antioxidant capacity from
different chocolate manufacturing stages using the NP-HPLC-online-DPPH
methodology.
AB - Cocoa beans are a well-known source of antioxidant polyphenols. Especially
individual oligomeric proanthocyanidins demonstrated a significant contribution
to the total antioxidant activity of cocoa compared to monomeric compounds. An NP
HPLC-online-DPPH assay was developed for separating the homologous series of
oligomeric proanthocyanidins and the simultaneous assessment of their antioxidant
capacity in relation to the degree of polymerization (DP). The present study
describes the influence of the different stages of a lab-scale chocolate
manufacturing process on the content of oligomeric proanthocyanidins and their
antioxidant capacity. The sum of the total proanthocyanidin content (? DP1-DP13)
decreased from 30mg epicatechin equivalents per gram non-fat dry matter in raw
fresh cocoa beans to 6mg epicatechin equivalents per gram in the final chocolate.
The antioxidant capacity decreased accordingly from 25mg epicatechin equivalents
per gram non-fat dry matter in raw fresh cocoa beans to 4mg/g in the final
chocolate product.
PMID- 27507507
TI - Effects of germination and high hydrostatic pressure processing on mineral
elements, amino acids and antioxidants in vitro bioaccessibility, as well as
starch digestibility in brown rice (Oryza sativa L.).
AB - The effects of germination and high hydrostatic pressure (HHP) processing on the
in vitro bioaccessibility of mineral elements, amino acids (AAs), antioxidants
and starch in brown rice (BR) were investigated. Germinated BR (GBR) was obtained
by incubating at 37 degrees C for 36h and then subjected to HHP treatments at
0.1, 100, 300 and 500MPa for 10min. The in vitro bioaccessibility of calcium and
copper was increased by 12.59-52.17% and 2.87-23.06% after HHP, respectively, but
bioaccessible iron was decreased. In addition, HHP significantly improved
individual AAs, particularly indispensable AAs and gama-aminobutyric acid, as
well as bioaccessible total antioxidant activities and starch resistance to
enzymatic hydrolysis. However, germination greatly increased starch
digestibility. Atomic force microscopy characterization suggested an obvious
structural change in bran fraction at pressures above 300MPa. These results can
help to understand the effects of germination and HHP technologies on nutrients
bioaccessibility and develop appropriate processing conditions.
PMID- 27507508
TI - Effects of chitin nano-whiskers on the gelatinization and retrogradation of maize
and potato starches.
AB - Starch is very prone to retrogradation after gelatinization. Inhibition of starch
retrogradation has been an important factor in improving the quality of food. For
the first time, we investigated the effect of nano-materials, represented by
chitin nano-whiskers (CNWs), on the short- and long-term retrogradation of maize
and potato starches. Rapid Visco-Analyser results showed that the addition of
CNWs significantly decreased the setback values of maize and potato starches,
which suggested that CNWs could retard the short-term retrogradation of starch.
Differential scanning calorimetry and X-ray diffraction results showed that the
percentage of retrogradation of maize and potato starches significantly decreased
(P<0.05), suggesting the inhibition of long-term retrogradation. The CNWs could
be used as a new inhibitor of starch retrogradation to develop starch-based food
with longer shelf life.
PMID- 27507509
TI - Biochemical composition and antioxidant activities of Arthrospira (Spirulina)
platensis in response to gamma irradiation.
AB - Arthrospira (Spirulina) platensis is a blue-green alga, rich with bioactive
components and nutrients. To evaluate effect of gamma irradiation, A. platensis
was exposed to different doses of 0.0, 0.5, 1.0, 1.5, 2.0 and 2.5kGy. The data
showed that the phenolic and proline contents significantly increased with the
increase of gamma irradiation doses up to 2.0kGy, above which a reduction was
observed. The soluble proteins and malondialdehyde (MDA) contents were stimulated
by all tested irradiation doses. Furthermore, the vitamins (A, K and B group) and
mineral contents (N, P, Na, K, Ca, Mg and Fe) were stimulated by the irradiation
doses compared with the control. The activities of some N-assimilating and
antioxidant enzymes were significantly increased with the irradiation doses up to
2.0kGy. This study suggests the possible use of gamma irradiation as a
stimulatory agent to raise the nutritive value and antioxidant activity of A.
platensis.
PMID- 27507510
TI - Synthesis of some glucose-fatty acid esters by lipase from Candida antarctica and
their emulsion functions.
AB - The synthesis of glucose esters with palmitic acid, lauric acid and hexanoic acid
using lipase enzyme was studied and their emulsion functionality in oil-in-water
system were compared. Reactions at 3:1M ratio of fatty acids-to-glucose had the
highest conversion percentages (over 90% for each of the fatty acid). Initial
conversion rate increased as substrate solubility increased. Ester bond formation
was confirmed by nuclear magnetic resonance technique that the chemical shifts of
glucose H-6 and alpha-carbon protons of fatty acids in the ester molecules
shifted to the higher fields. Contact angle of water on esters' pelleted surface
increased as the hydrophobicity increased. Glucose esters' and commercial sucrose
esters' functionality as emulsifiers were compared. Glucose esters delayed, but
did not prevent coalescence, because the oil droplets diameter doubled during
7days. Sucrose esters prevented coalescence during 7days since the droplets
diameter did not have significant change.
PMID- 27507511
TI - Pressurized liquid extraction of anthocyanins and biflavonoids from Schinus
terebinthifolius Raddi: A multivariate optimization.
AB - Response surface methodology was employed to investigate the effects of
pressurized liquid extraction (PLE) parameters on the recovery of phenolic
compounds (anthocyanins, biflavonoids) from Brazilian pepper (Schinus
terebinthifolius Raddi) fruits. The effects of temperature, static time, and
ethanol as well as acid concentration on the polyphenol yield were described well
by quadratic models (p<0.0001). A significant influence of the ethanol
concentration (p<0.0001) and several interactions (p<0.05) were identified.
Identification of the biflavonoid I3',II8-binaringenin in drupes of S.
terebinthifolius was achieved by UHPLC-MS(2). Interestingly, at high extraction
temperatures (>75 degrees C), an artifact occurred and was tentatively identified
as a diastereomer of I3',II8-binaringenin. Multivariate optimization led to high
yields of phenolic compounds from the exocarp/drupes at 100/75 degrees C,
10/10min, 54.5/54.2% ethanol, and 5/0.03% acetic acid. This study demonstrates
that PLE is well suited for the extraction of phenolic compounds from S.
terebinthifolius and can efficiently be optimized by response surface
methodology.
PMID- 27507512
TI - Antidiabetic activity and chemical constituents of the aerial parts of Heracleum
dissectum Ledeb.
AB - Heracleum dissectum Ledeb. has long been used as a wild edible vegetable by local
people in China. The purpose of this study is to investigate the antidiabetic
potential of aerial part of H. dissectum methanol extract (HdME) and the chemical
constituents. Ten compounds including eight coumarins were isolated and four of
them were found from H. dissectum for the first time. HdME potently inhibited the
elevation of plasma glucose after its oral administration to glucose-loaded mice,
and its petroleum ether (PE) fraction exerted the greatest inhibitory activities.
Meanwhile, HdME (125 and 250mg/kg) also significantly decreased the blood glucose
level in STZ-induced diabetic mice, but had no effect in normoglycemic mice.
Additionally, HdME showed weak inhibitory effects on alpha-glucosidase activity
and DPPH free radicals scavenging. In conclusion, HdME has antidiabetic action
and PE fraction is the active part where coumarins possibly play an important
role in antidiabetic activity.
PMID- 27507513
TI - Sulforaphane formation and bioaccessibility are more affected by steaming time
than meal composition during in vitro digestion of broccoli.
AB - Broccoli is a rich source of the glucosinolate glucoraphanin (GR). After
hydrolysis of GR by the endogenous enzyme myrosinase, sulforaphane (SF) or
sulforaphane nitrile (SFN) are produced, depending on environmental conditions.
How the conversion of GR and bioaccessibility of released breakdown products are
affected by steaming (raw, 1min, 2min and 3min steamed) and meal composition
(protein or lipid addition) was studied with an in vitro digestion model (mouth,
stomach, intestine, but not colonic digestion). The main formation of SF and SFN
occurred during in vitro chewing. The contents of GR, SF and SFN did not change
after further digestion, as the irreversible inactivated myrosinase under gastric
conditions caused no further GR hydrolysis. SF concentrations were up to 10 times
higher in raw and 1min steamed broccoli samples after digestion compared to
longer-steamed broccoli. Protein or lipid addition had no influence on the
formation and bioaccessibility of SF or SFN.
PMID- 27507514
TI - Simultaneous determination of individual isothiocyanates in plant samples by HPLC
DAD-MS following SPE and derivatization with N-acetyl-l-cysteine.
AB - The procedure for the isothiocyanates (ITCs) determination that involves
derivatization with N-acetyl-l-cysteine (NAC) and separation by HPLC was
developed. Prior to derivatization, plant ITCs were isolated and purified using
solid-phase extraction (SPE). The optimum conditions of derivatization are:
500MUL of isopropanolic eluate obtained by SPE combined with 500MUL of
derivatizing reagent (0.2M NAC and 0.2M NaHCO3 in water) and reaction time of 1h
at 50 degrees C. The formed dithiocarbamates are directly analyzed by HPLC
coupled with diode array detector and mass spectrometer if required. The method
was validated for nine common natural ITCs. Calibration curves were linear
(R(2)?0.991) within a wide range of concentrations and limits of detection were
below 4.9nmol/mL. The recoveries were in the range of 83.3-103.7%, with relative
standard deviations <5.4%. The developed method has been successfully applied to
determine ITCs in broccoli, white cabbage, garden cress, radish, horseradish and
papaya.
PMID- 27507515
TI - Oxidation of proline decreases immunoreactivity and alters structure of barley
prolamin.
AB - Elimination of celiac-toxic prolamin peptides and proteins is essential for
Triticeae products to be gluten-free. Instead of enzymatic hydrolysis, in this
study we investigated metal-catalyzed oxidation of two model peptides, QQPFP, and
PQPQLPY, together with a hordein isolate from barley (Hordeum vulgare L.). We
established a multiple reaction monitoring (MRM) LC-MS method to detect and
quantify proline oxidation fragments. In addition to fragmentation, aggregation
and side chain modifications were identified, including free thiol loss, carbonyl
formation, and dityrosine formation. The immunoreactivity of the oxidized hordein
isolate was considerably decreased in all metal-catalyzed oxidation systems.
Cleavage of peptides or protein fragments at the numerous proline residues
partially accounts for the decrease. Metal-catalyzed oxidation can thus be used
in the modification and elimination of celiac-toxic peptides and proteins.
PMID- 27507516
TI - Comparing the calcium bioavailability from two types of nano-sized enriched milk
using in-vivo assay.
AB - Calcium bioavailability from two types of enriched (calcium citrate and calcium
carbonate) milks homogenized to a nano-sized particle distribution has been
studied among 48 female Sprauge-dawley rats. Skim milk powder was enriched with
some essential nutrients (Inulin, DHA & EPA, vitamins B6, K1, and D3) as
enhancers of calcium bioavailability according to recommended dietary allowances
of the West European and North American. Ovariectomized and ovariectomized
osteoporosis rats were used as a menopause and menopause-osteoporosis model,
respectively. Although, nano-sized enriched milk powders had the greatest calcium
bioavailability among the groups, but bioavailability of nano-sized calcium
carbonate-enriched-milk was significantly (P<0.05) better than nano-sized calcium
citrate-enriched-milk. Moreover, the trends were similar for bone calcium,
strength and morphology. Therefore, based on the current results the calcium
carbonate nano-sized enriched milk could be an effective enriched milk powder in
ovariectomized-osteoporosis and ovariectomized rats as a model of menopause
osteoporosis and menopause women.
PMID- 27507517
TI - Characterization and emulsifying properties of beta-lactoglobulin-gum Acacia
Seyal conjugates prepared via the Maillard reaction.
AB - Gum Acacia Seyal (ASY) is less valued than is gum Acacia Senegal, due to its poor
emulsifying ability. The present study investigated the Maillard reaction between
ASY and beta-lactoglobulin (BLG) and its impact on the emulsifying properties of
ASY. The reaction products of BLG/ASY mixture (r=1/4), prepared by dry-heating at
60 degrees C and a relative humidity of 79%, as a function of incubation time,
were characterized by SDS-PAGE, GPC-MALLS and DSC. The results showed that 12-24h
of dry-heating under the given conditions was sufficient for conjugation,
meanwhile avoiding the formation of deeply coloured and insoluble melanoidins.
More than 64% of the protein was incorporated into ASY, resulting in a two-fold
increase in arabinogalactan-protein (AGP) content and 3.5 times increase in
weight-average molecular mass of ASY. The conjugation with BLG markedly improved
the stability of ASY-stabilized emulsions and their resistance against severe
conditions, such as low pH and high saline conditions.
PMID- 27507518
TI - Extraction of espresso coffee by using gradient of temperature. Effect on
physicochemical and sensorial characteristics of espresso.
AB - Espresso extraction is generally carried out at a fixed temperature within the
range 85-95 degrees C. In this work the extraction of the espressos was made in a
new generation coffee machine that enables temperature profiling of the brewing
water. The effect of using gradient of temperature to brew espressos on
physicochemical and sensorial characteristics of the beverage has been
investigated. Three different extraction temperature profiles were tested:
updrawn gradient (88-93 degrees C), downdrawn gradient (93-88 degrees C) and
fixed temperature (90 degrees C). The coffee species investigated were Robusta,
Arabica natural and Washed Arabica. Results proved that the use of gradient
temperature for brewing espressos allows increasing or decreasing the extraction
of some chemical compounds from coffee grounds. Moreover an appropriate gradient
of temperature can highlight or hide some sensorial attributes. In conclusion,
the possibility of programming gradient of temperature in the coffee machines
recently introduced in the market opens new expectations in the field of espresso
brewing.
PMID- 27507519
TI - NGS tools for traceability in candies as high processed food products: Ion
Torrent PGM versus conventional PCR-cloning.
AB - The Next Generation Sequencing methodologies are considered the next step within
DNA-based methods and their applicability in different fields is being evaluated.
Here, we tested the usefulness of the Ion Torrent Personal Genome Machine (PGM)
in food traceability analyzing candies as a model of high processed foods, and
compared the results with those obtained by PCR-cloning-sequencing (PCR-CS). The
majority of samples exhibited consistency between methodologies, yielding more
information and species per product from the PGM platform than PCR-CS.
Significantly higher AT-content in sequences of the same species was also
obtained from PGM. This together with some taxonomical discrepancies between
methodologies suggest that the PGM platform is still pre-mature for its use in
food traceability of complex highly processed products. It could be a good option
for analysis of less complex food, saving time and cost per sample.
PMID- 27507520
TI - A food waste utilization study for removing lead(II) from drinks.
AB - This is the first study about removal of lead (Pb(II)) from energy drinks. In
this paper, food waste, namely eggshell (hydroxyapatite) utilization, was used to
remove Pb(II) from mineral water and energy drinks. Mineral water and energy
drinks were chosen for removal of lead since the latter is severely hazardous to
human health even in small amounts. Response Surface Methodology (RSM) was
performed to optimize the application process by practice of the quadratic model
united with the Central Composite Design (CCD) and quadratic combined program was
utilized to study the most effective parameters on aforementioned liquids.
Through the application of variance analysis (ANOVA) factors critical to removing
of lead were identified for each experimental design response. Maximum adsorption
capacity of eggshell was achieved as 923mgg(-1) for Pb(II). The obtained optimum
conditions were applied to drinks. Results showed that used adsorbent was quite
effective in removing Pb(II) from drinks.
PMID- 27507521
TI - Polyphenols from wolfberry and their bioactivities.
AB - Nine new phenylpropanoids, one new coumarin, and 43 known polyphenols were
isolated from wolfberry. Their structures were determined by spectroscopic
analyses, chemical methods, and comparison of NMR data. Polyphenols, an important
type of natural products, are notable constituents in wolfberry. 53 polyphenols,
including 28 phenylpropanoids, four coumarins, eight lignans, five flavonoids,
three isoflavonoids, two chlorogenic acid derivatives, and three other
constituents, were identified from wolfberry. Lignans and isoflavonoids were
firstly reported from wolfberry. 22 known polyphenols were the first isolates
from the genus Lycium. This research presents a systematic study on wolfberry
polyphenols, including their bioactivities. All these compounds exhibited oxygen
radical absorbance capacity (ORAC), and some compounds displayed DPPH radical
scavenging activity. One compound had acetylcholinesterase inhibitory activity.
The discovery of new polyphenols and their bioactivities is beneficial for
understanding the scientific basis of the effects of wolfberry.
PMID- 27507522
TI - Effects of micronisation and dehulling of pre-soaked bambara groundnut seeds on
microstructure and functionality of the resulting flours.
AB - Functional properties of flours from pre-soaked and micronised (130 degrees C)
whole and dehulled bambara seeds (5, 10 and 15min) were determined. An increase
in micronisation time significantly reduced the pasting viscosity of the flours.
Significant reductions in the differential scanning calorimetry endothermic peak
enthalpies and loss of birefringence in the starch were found, indicating starch
pre-gelatinisation when micronised. The low viscous paste of resultant flours
seems to be related to protein denaturation as shown by decrease in nitrogen
solubility index. Starch was embedded in a protein matrix as shown by confocal
laser scanning microscopy. This denatured protein matrixes could be in part
preventing starch hydration and dispersion during pasting and thus reduced
viscosity. Dehulling reduced the pasting viscosity suggesting higher effect of
micronisation for dehulled than whole samples. Resulting flours can be useful
ingredients in protein energy-dense foods due to low viscosity.
PMID- 27507523
TI - Chip-based molecularly imprinted monolithic capillary array columns coated
GO/SiO2 for selective extraction and sensitive determination of rhodamine B in
chili powder.
AB - A novel solid-phase extraction chip embedded with array columns of molecularly
imprinted polymer-coated silanized graphene oxide (GO/SiO2-MISPE) was established
to detect trace rhodamine B (RB) in chili powder. GO/SiO2-MISPE monolithic
columns for RB detection were prepared by optimizing the supporting substrate,
template, and polymerizing monomer under mild water bath conditions. Adsorption
capacity and specificity, which are critical properties for the application of
the GO/SiO2-MISPE monolithic column, were investigated. GO/SiO2-MIP was examined
by scanning electron microscopy (SEM) and Fourier transform-infrared
spectroscopy. The recovery and the intraday and interday relative standard
deviations for RB ranged from 83.7% to 88.4% and 2.5% to 4.0% and the enrichment
factors were higher than 110-fold. The chip-based array columns effectively
eliminated impurities in chili powder, indicating that the chip-based GO/SiO2
MISPE method was reliable for RB detection in food samples using high-performance
liquid chromatography. Accordingly, this method has direct applications for
monitoring potentially harmful dyes in processed food.
PMID- 27507524
TI - A comprehensive evaluation of three microfluidic chemiluminescence methods for
the determination of the total phenolic contents in fruit juices.
AB - Three recently reported microfluidic chemiluminescence (MF-CL) methods (based on
reactions with acidic permanganate enhanced by formaldehyde (KMnO4-COH), acidic
cerium (IV) and rhodamine B (Ce-RB), and acidic cerium (IV) and rhodamine 6G (Ce
R6G) enhanced by SDS) for the determination of the total phenolic content (TPC)
in juices were critically evaluated in terms of their selectivity. The evaluation
was carried out using 86 analytes, including 22 phenolic compounds (phenolic
acids and polyphenols), 6 known non-phenolic antioxidants, 9 amino acids and a
number of proteins, carbohydrates, nucleotide bases, inorganic salts and other
compounds. Each method was sensitive toward phenolic compounds (PCs). However,
the KMnO4-COH CL system showed a higher sensitivity toward phenolic acids and
also responded to non-phenolic antioxidants. The other two systems showed higher
sensitivity toward polyphenolic compounds than to phenolic acids and did not
responded to all other compounds including non-phenolic antioxidants.
PMID- 27507525
TI - HPLC-DAD-ESI/MS(n) profiling of phenolic compounds from Lathyrus cicera L. seeds.
AB - Lathyrus cicera L. seeds are of interest for food and feed purposes. Despite the
recognized antioxidant activity of the seeds, arising from the phenolic fraction,
their phenolic compounds have not been studied in depth yet. Therefore, to
determine the phenolics profile of these seeds, a target analysis was performed
using high-performance liquid chromatography coupled to photodiode-array
detection and electrospray ionization/ion trap mass spectrometry (HPLC-DAD
ESI/MS(n)). Thirty-seven glycosylated flavonoids were identified for the first
time in the seeds of this species and, according to their MS fragmentation,
clustered in flavonol-3-O-di-/tri-glycosides-7-O-rhamnosides and other flavonol
glycosides, and flavonol-3-O-(cinnamoyl)glycoside-7-O-rhamnosides, flavonol-3-O
(dihydrophaseoyl, cinnamoyl)glycoside-7-O-rhamnosides and flavonol-3-O
(malonyl)glycoside-7-O-rhamnosides. Glycosides of kaempferol were the main
flavonoids found (10 non-acylated and 21 acylated), followed by those of
quercetin (3) and those of isorhamnetin, apigenin and luteolin (1). The most
abundant flavonols were identified as kaempferol-3-O-(2-hexosyl)hexoside-7-O
rhamnosides. The methodology used allowed to increase the knowledge on a relevant
phytochemical class of seeds from L. cicera.
PMID- 27507526
TI - A fast and environment-friendly MEPSPEP/UHPLC-PDA methodology to assess 3-hydroxy
4,5-dimethyl-2(5H)-furanone in fortified wines.
AB - Sotolon is widely associated with the quality of fortified aged wines, and has
also been linked to premature oxidative aging (premox). Here we developed a
single, fast and environmental-friendly microextraction by packed sorbent ultra
high pressure liquid chromatography analysis (MEPS/UHPLC-PDA) for sotolon
quantification in different wines. The best extraction conditions (loading three
times 250MUL samples through the MEPSPEP sorbent and elution with 100MUL of 50%
MeOH) were combined with a fast UHPLC separation (5min separation using acidified
10% MeOH isocratic flow in a CORTECS C18 column) to allow unparalleled minimum
sample and solvents volumes usage. The validated methodology showed good
linearity (r(2)>0.993) and precision (<5.6%); high recovery (>81%) and detection
limits (0.45-2.51MUg/L) far below sotolon odor threshold for any type of wine.
The methodology was successfully applied to selected white table and Madeira
wines, encompassing therefore a wide range of alcohol and sugar contents.
Furthermore, as far we may know, this is the first time a single methodology can
be used to assess both wine aging or premox according to the type of wine.
PMID- 27507527
TI - Quality assessment of 178 cultivars of plum regarding phenolic, anthocyanin and
sugar content.
AB - In this study assessment of total phenolic, individual anthocyanin and total
sugar content (TSC) of wide range of plum cultivars was done in order to select
cultivars with high health benefiting compounds for potential breeding purposes.
Total phenolics varied between 38.45 and 841.50mg GAE 100g(-1) FW. Cyaniding-3
rutinoside, cyaniding-3- glucoside and its equivalents were identified in
anthocyanin measurement by HPLC with different ranges. TSC differed between 9.63
and 29.47%. Besides, evaluation of the effect of cultivar and year on phenolic
content of 23 randomly selected cultivars over two following years (2013 & 2014)
showed significant effect of both factors on phenolic content of plum cultivars.
Overall, cultivars "Cacaks Spaete" which had high amount of total phenolics with
stability over time, as well as "Hohenheim breed 4894" as a cultivar which
contained high amounts of total phenolics, anthocyanins and TSC were selected for
further breeding purposes to provide high nutritional quality plum to consumers.
PMID- 27507528
TI - Effect of pullulan on the water distribution, microstructure and textural
properties of rice starch gels during cold storage.
AB - The effects of pullulan on the water distribution, microstructure and textural
properties of rice starch gels during cold storage were investigated by low field
nuclear magnetic resonance (LF-NMR), scanning electron microscope (SEM), and
texture profile analysis (TPA). The addition of pullulan reduced the transversal
relaxation time of rice starch gels during cold storage. The microstructure of
rice starch gel with 0.5% pullulan was denser and more uniform compared with that
of rice starch without pullulan in each period of storage time. With regard to
textural properties, 0.01% pullulan addition did not significantly change the
texture of rice starch gels, while 0.5% pullulan addition appeared to reduce the
hardness and retain the springiness of rice starch gels (P?0.05). The restriction
effects of pullulan on water mobility and starch retrogradation were hypothesized
to be mainly responsible for the water retention, gel structure maintenance, and
modification of the textural attributes of rice starch gels.
PMID- 27507529
TI - Effect of trypsin treatments on the structure and binding capacity of volatile
compounds of myosin.
AB - In order to investigate the mechanism between flavor binding and proteins
degradation during meat processing, the influence of different trypsin contents
on the structure of myosin and the adsorption capacity on aldehydes and ketones
was determined. The 1% treatment produced subfragment 2 (S2), light meromyosin
(LMM) and decreased 18 and 16kDa light chains; 5% and 10% treatments produced 100
and 65kDa new bands and more S2, LMM and cleaned light chains. With the rising
trypsin contents, beta-sheet, beta-turn, random coil, hydrophobicity and total
sulfydryl content increased; solubility, alpha-helix and free percentages of
aldehydes and ketones decreased. The increase of absorbing capacity could be
attributed to the increased hydrophobicity and total sulphydryl and the unfolding
of secondary structures by exposing reactive amino and thiol groups and
hydrophobic sites; the decreased solubility was related to the increased
hydrophobicity. The trypsin-dose dependent proteolysis of myosin increased the
retention of volatile compounds.
PMID- 27507530
TI - Chemical profiling of the major components in natural waxes to elucidate their
role in liquid oil structuring.
AB - Elucidating the composition of waxes is of utmost importance to explain their
behavior in liquid oil structuring. The chemical components (hydrocarbons - HCs,
free fatty acids - FFAs, free fatty alcohols - FALs and wax esters - WEs) of
natural waxes were analyzed using HPLC-ELSD and GC-MS followed by evaluation of
their oil structuring properties. The gel strength, including the average storage
modulus and oscillation yield stress, displayed a negative correlation with FALs
and a positive correlation with HCs, FFAs and WEs. The components dictating the
gel strength are HCs, FFAs and WEs in a descending order of importance. The
consistency of the oleogels increased with the increasing amount of FFAs and HCs
and the decreasing amount of WEs and FALs. The presence of more WEs results in a
strong but brittle gel with a high initial flow yield stress. We believe these
results might be useful in selecting the right waxes to combine in certain fat
based food products.
PMID- 27507531
TI - Chemo-enzymatic synthesis of vinyl and l-ascorbyl phenolates and their inhibitory
effects on advanced glycation end products.
AB - This study successfully established the feasibility of a two-step chemo-enzymatic
synthesis of l-ascorbyl phenolates. Intermediate vinyl phenolates were first
chemically produced and then underwent trans-esterification with l-ascorbic acid
in the presence of Novozyme 435(r) (Candida Antarctica lipase B) as a catalyst.
Twenty vinyl phenolates and 11 ascorbyl phenolates were subjected to in vitro
bioassays to investigate their inhibitory activity against advanced glycation end
products (AGEs). Among them, vinyl 4-hydroxycinnamate (17VP), vinyl 4-hydroxy-3
methoxycinnamate (18VP), vinyl 4-hydroxy-3,5-dimethoxycinnamate (20VP), ascorbyl
4-hydroxy-3-methoxycinnamate (18AP) and ascorbyl 3,4-dimethoxycinnamate (19AP)
showed 2-10 times stronger inhibitory activities than positive control
(aminoguanidine and its precursors). These results indicated that chemo
enzymatically synthesized compounds have AGE inhibitory effect and thus are
effective in either preventing or retarding glycation protein formation.
PMID- 27507532
TI - Pinot noir wine volatile and anthocyanin composition under different levels of
vine fruit zone leaf removal.
AB - The impacts of fruit zone leaf removal on volatile and anthocyanin compositions
of Pinot noir wine were investigated over two growing seasons. Wine volatiles
were analyzed by multiple techniques, including headspace solid phase
microextraction-GC-MS (HS-SPME-GC-MS), headspace-GC-FID (HS-GC-FID) and stir bar
sorptive extraction-GC-MS (SBSE-GC-MS). Fruit zone leaf removal affected the
concentration of many grape-derived volatile compounds such as terpene alcohols
and C13-norisoprenoids in wine, although the degree of impact depended on the
vintage year and severity of leaf removal. Fruit zone leaf removal resulted in
greater concentrations of linalool, alpha-terpineol and beta-damascenone but had
no impact on other terpene alcohols or beta-ionone. Fruit zone leaf removal had
no consistent impact on C6 alcohols, volatile phenols, lactones, fermentation
derived alcohols, acids, or most esters. Fruit zone leaf removal increased
anthocyanins in final wine.
PMID- 27507533
TI - Corrigendum to "New steroidal saponins and antiulcer activity from Solanum
paniculatum L." [Food Chem. 186 (2015) 160-167].
PMID- 27507535
TI - Investigation of Ca substitution on the gas sensing potential of LaFeO3
nanoparticles towards low concentration SO2 gas.
AB - The present work investigates the superior ability of LaFeO3 (LaFeO) and
La0.8Ca0.2FeO2.95 (LaCaFeO) nanoparticles to detect 3 ppm SO2 gas. The influence
of calcium substitution on the sensing behaviour of LaFeO has been studied. High
resolution TEM images show that the particle sizes of LaFeO and LaCaFeO are less
than 100 nm and SEM images show the agglomeration of interconnected
nanoparticles. Both LaFeO and LaCaFeO crystallize in the orthorhombic crystal
system with the space group Pbnm. Rietveld analysis of neutron diffraction data
showed that LaCaFeO has lattice oxygen vacancies. In addition, magnetic
refinements on both the samples have been carried out. The presence of lattice
oxygen vacancies in LaCaFeO is qualitatively supported by Raman and XPS
measurements. Electrical characterization showed increased conductivity for the
LaCaFeO sample, influencing their sensing performance significantly. The LaCaFeO
nanoparticles exhibit higher sensitivity, faster response time, rapid recovery
time and good recyclability for sensing 3 ppm SO2 gas. This enhanced sensing
behaviour is attributed to the increased oxygen vacancies in the lattice as well
as the surface. As a consequence, increased active sites are created in LaCaFeO,
promoting redox reaction between the analyte and the sensing material. The
results demonstrated that while LaFeO is a good gas sensor, p-type substitution
by Ca(2+) renders this material an improved resistivity based gas sensor to
detect low concentration SO2.
PMID- 27507534
TI - Diagnostic imaging and cataloguing of female genital malformations.
AB - To help physicians and radiologists in the diagnosis of female genito-urinary
malformations, especially of complex cases, the embryology of the female genital
tract, the basis for Mullerian development anomalies, the current classifications
for such anomalies and the comparison for inclusion and cataloguing of female
genital malformations are briefly reviewed. The use of the embryological system
to catalogue female genito-urinary malformations may ultimately be more useful in
correlations with clinical presentations and in helping with the appropriate
diagnosis and treatment. Diagnostic imaging of the different genito-urinary
anomalies are exposed, placing particular emphasis on the anomalies within group
II of the embryological and clinical classification (distal mesonephric
anomalies), all of them associated with unilateral renal agenesis or dysplasia.
Similarly, emphasis is placed on cases of cervico-vaginal agenesis, cavitated
noncommunicated uterine horns, and cloacal and urogenital sinus anomalies and
malformative combinations, all of them complex malformations. Diagnostic imaging
for all these anomalies is essential. The best imaging tools and when to evaluate
for other anomalies are also analysed in this review. TEACHING POINTS: * The
appropriate cataloguing of female genital malformations is controversial. * An
embryological classification system suggests the best diagnosis and appropriate
management. * The anomalies most frequently diagnosed incorrectly are the distal
mesonephric anomalies (DMAs). * DMAs are associated with unilateral renal
agenesis or renal dysplasia with ectopic ureter. * We analyse other complex
malformations. Diagnostic imaging for these anomalies is essential.
PMID- 27507536
TI - Fruits and vegetables are incorporated into home cuisine in different ways that
are relevant to promoting increased consumption.
AB - Fruits and vegetables are essential for healthy life. We examined the fruits and
vegetables consumption by 240 caregivers and their children aged 1-17 years in
peri-urban Lima, and the ways that they were incorporated into local cuisine. A
randomized cross-sectional household survey collected information on the weight
of all foods eaten the previous day (24 h) including fruits and vegetables, their
preparation and serving sizes. Fruit and vegetable consumption was low and very
variable: fruit intake was mean 185.2 +/- 171.5 g day-1 , median 138 g day-1 for
caregivers and 203.6 +/- 190.6 g day-1 and 159 g day-1 for children, vegetable
intake was mean 116.9 +/- 94.0 g day-1 median 92 g day-1 for caregivers, mean
89.3 +/- 84.7 g day-1 median 60 g day-1 for children. Only 23.8% of children and
26.2% of caregivers met the recommended >=400 g of fruit or vegetable/day.
Vegetables were mainly eaten either as ingredients of the main course recipe,
eaten by about 80% of caregivers and children, or as salads eaten by 47% of
caregivers and 42% of children. Fruits were most commonly eaten as whole fresh
fruits eaten by 68% of caregivers and 75% of children. In multivariate analysis
of the extent to which different presentations contributed to daily fruit and
vegetable consumption, main courses contributed most to determining vegetable
intake for caregivers, and for children, main course and salads had similar
contributions. For fruit intake, the amount eaten as whole fruit determined total
fruit and total fruit plus vegetable intake for both caregivers and children.
Local cuisine should be considered in interventions to promote fruit and
vegetable consumption. (c) 2016 John Wiley & Sons Ltd.
PMID- 27507537
TI - Characterization of a re-engineered, mesothelin-targeted Pseudomonas exotoxin
fusion protein for lung cancer therapy.
AB - Mesothelin overexpression in lung adenocarcinomas correlates with the presence of
activating KRAS mutations and poor prognosis. Hence SS1P, a mesothelin-targeted
immunotoxin, could offer valuable treatment options for these patients, but its
use in solid tumor therapy is hampered by high immunogenicity and non-specific
toxicity. To overcome both obstacles we developed RG7787, a de-immunized
cytotoxic fusion protein comprising a humanized SS1 Fab fragment and a truncated,
B-cell epitope silenced, 24 kD fragment of Pseudomonas exotoxin A (PE24).
Reactivity of RG7787 with sera from immunotoxin-treated patients was >1000 fold
reduced. In vitro RG7787 inhibited cell viability of lung cancer cell lines with
picomolar potency. The pharmacokinetic properties of RG7787 in rodents were
comparable to SS1P, yet it was tolerated up to 10 fold better without causing
severe vascular leak syndrome or hepatotoxicity. A
pharmacokinetic/pharmacodynamic model developed based on NCI-H596 xenograft
studies showed that for RG7787 and SS1P, their in vitro and in vivo potencies
closely correlate. At optimal doses of 2-3 mg/kg RG7787 is more efficacious than
SS1P. Even large, well established tumors (600 mm(3)) underwent remission during
three treatment cycles with RG7787. Also in two patient-derived lung cancer
xenograft models, Lu7336 and Lu7187, RG7787 showed anti-tumor efficacy. In
monotherapy two treatment cycles were moderately efficacious in the Lu7336 model
but showed good anti-tumor activity in the KRAS mutant Lu7187 model (26% and 80%
tumor growth inhibition, respectively). Combination of RG7787 with standard
chemotherapies further enhanced efficacy in both models achieving near complete
eradication of Lu7187 tumors.
PMID- 27507539
TI - Structural basis for Myf and Psa fimbriae-mediated tropism of pathogenic strains
of Yersinia for host tissues.
AB - Three pathogenic species of the genus Yersinia assemble adhesive fimbriae via the
FGL-chaperone/usher pathway. Closely related Y. pestis and Y. pseudotuberculosis
elaborate the pH6 antigen (Psa), which mediates bacterial attachment to alveolar
cells of the lung. Y. enterocolitica, instead, assembles the homologous fimbriae
Myf of unknown function. Here, we discovered that Myf, like Psa, specifically
recognizes beta1-3- or beta1-4-linked galactose in glycosphingolipids, but
completely lacks affinity for phosphatidylcholine, the main receptor for Psa in
alveolar cells. The crystal structure of a subunit of Psa (PsaA) complexed with
choline together with mutagenesis experiments revealed that PsaA has four
phosphatidylcholine binding pockets that enable super-high-avidity binding of Psa
fibres to cell membranes. The pockets are arranged as six tyrosine residues,
which are all missing in the MyfA subunit of Myf. Conversely, the crystal
structure of the MyfA-galactose complex revealed that the galactose-binding site
is more extended in MyfA, enabling tighter binding to lactosyl moieties. Our
results suggest that during evolution, Psa has acquired a tyrosine-rich surface
that enables it to bind to phosphatidylcholine and mediate adhesion of Y.
pestis/pseudotuberculosis to alveolar cells, whereas Myf has specialized as a
carbohydrate-binding adhesin, facilitating the attachment of Y. enterocolitica to
intestinal cells.
PMID- 27507538
TI - MiR-31 and miR-128 regulates poliovirus receptor-related 4 mediated measles virus
infectivity in tumors.
AB - Oncolytic measles virus strains are currently being evaluated in several clinical
trials, as a promising novel oncolytic platform. Poliovirus receptor-related 4
(PVRL4) was recently identified as a potent measles virus (MV) receptor; however,
its regulation is not yet understood. Increased levels of PVRL4 protein were
observed in cell membrane, cytoplasm and nuclei of glioblastoma, breast and
ovarian tumor clinical samples with no significant change in PVRL4 mRNA levels in
glioblastoma and breast cancer compared with their corresponding control samples,
suggesting that PVRL4 is likely post-transcriptionally regulated. Therefore, we
sought to investigate the potential role of miRNAs in PVRL4 regulation and thus
MV infectivity. We demonstrated that miR-31 and miR-128 can bind to the 3'UTR of
PVRL4 and decrease PVRL4 levels while anti-miR-31/128 increase PVRL4 levels
suggesting that PVRL4 is miRNA targeted. Furthermore, miR-31/128 expression
levels were down-regulated in glioblastoma and breast tumor samples and showed
significant negative correlations with PVRL4 levels. Infection with an MV strain
that exclusively utilizes PVRL4 as its receptor showed that over-expression of
miR-31/128 decreases MV infectivity while inhibition of the respective miRNAs via
anti-miRs increase MV infectivity and reduce tumor size in mouse xenograft models
of glioblastoma, breast and ovarian cancer. Additionally, miR-128 levels showed
significant correlations with MV infection and in vivo anti-tumor effect, while
MV infection increased miR-31 expression and thereby contributed to the observed
decrease in PVRL4 levels. This study suggests that PVRL4 is post
transcriptionally regulated by miR-128 and miR-31 and harbors possible miRNA
targets that could modulate MV infectivity and in turn enhance MV based oncolytic
therapeutic strategies.
PMID- 27507540
TI - Lifestyle medicine curriculum for a preventive medicine residency program:
implementation and outcomes.
AB - BACKGROUND: The vast majority of the healthcare problems burdening our society
today are caused by disease-promoting lifestyles (e.g., physical inactivity and
unhealthy eating). Physicians report poor training and lack of confidence in
counseling patients on lifestyle changes. OBJECTIVE: To evaluate a new curriculum
and rotation in lifestyle medicine for preventive medicine residents. METHODS:
Training included didactics (six sessions/year), distance learning, educational
conferences, and newly developed lifestyle medicine rotations at the Institute of
Lifestyle Medicine, the Yale-Griffin Prevention Research Center, and the
Integrative Medicine Center. We used a number of tools to assess residents'
progress including Objective Structured Clinical Examinations (OSCEs), self
assessments, and logs of personal health habits. RESULTS: A total of 20 residents
participated in the lifestyle medicine training between 2010 and 2013. There was
a 15% increase in residents' discussions of lifestyle issues with their patients
based on their baseline and follow-up surveys. The performance of preventive
medicine residents on OSCEs increased each year they were in the program (average
OSCE score: PGY1 73%, PGY2 83%, PGY3 87%, and PGY4 91%, p=0.01). Our internal
medicine and preliminary residents served as a control, since they did
participate in didactics but not in lifestyle medicine rotations. Internal
medicine and preliminary residents who completed the same OSCEs had a slightly
lower average score (76%) compared with plural for resident, preventive medicine
residents (80%). However, this difference did not reach statistical significance
(p=0.11). CONCLUSION: Incorporating the lifestyle medicine curriculum is feasible
for preventive medicine training allowing residents to improve their health
behavior change discussions with patients as well as their own personal health
habits.
PMID- 27507541
TI - Starting a new residency program: a step-by-step guide for institutions,
hospitals, and program directors.
AB - Although our country faces a looming shortage of doctors, constraints of space,
funding, and patient volume in many existing residency programs limit training
opportunities for medical graduates. New residency programs need to be created
for the expansion of graduate medical education training positions. Partnerships
between existing academic institutions and community hospitals with a need for
physicians can be a very successful means toward this end. Baylor College of
Medicine and The Children's Hospital of San Antonio were affiliated in 2012, and
subsequently, we developed and received accreditation for a new categorical
pediatric residency program at that site in 2014. We share below a step-by-step
guide through the process that includes building of the infrastructure,
educational development, accreditation, marketing, and recruitment. It is our
hope that the description of this process will help others to spur growth in
graduate medical training positions.
PMID- 27507542
TI - Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated
apoptosis.
AB - Previous reports have suggested that some probiotics inhibit tumorigenesis and
cancer progression. However, the molecules involved have not yet been identified.
Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a
strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry,
we identify ferrichrome as a tumour-suppressive molecule produced by L. casei
ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of
cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non
cancerous intestinal cells than either of those agents. A transcriptome analysis
reveals that ferrichrome treatment induces apoptosis, which is mediated by the
activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the
induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK
signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts
a tumour-suppressive effect via the JNK signalling pathway.
PMID- 27507543
TI - Surgical management of spinal fractures and neurological involvement in patients
with myeloma.
AB - INTRODUCTION: Multiple Myeloma (MM) typically involves the spine and causes bone
pain, pathological fractures and spinal cord compression with possible consequent
neurological deficits. This retrospective study reports the results of surgery on
a selected population of patients who underwent surgery for symptomatic spinal
myeloma. MATERIALS AND METHODS: A total of 26 patients who underwent surgery for
spinal myeloma with neurological involvement were studied retrospectively.
Neurological evaluation was performed according to the Frankel grade.
Characteristics of this population, reconstructive techniques and surgery-related
complications were reviewed. RESULTS: The tumours involved the thoracic spine in
13 patients, the lumbar spine in 10 patients, and the cervical spine in three
patients. The most common approach was a posterior-only approach (70%), followed
by a staged, combined approach (20%), and an anterior-only approach (10%). The
mean postoperative survival time was 43 months (range: 8-60 months). A
significant improvement in neurological function was observed in the study
population after surgery (p=0.001). There were seven early postoperative
complications, two late complications and five surgery-related complications.
DISCUSSION: Surgery in selected patients affected by spinal myeloma with
neurological involvement is associated with good clinical outcomes and
neurological recovery and an acceptable rate of complications. Neurological
deficit and segmental instability can be treated sufficiently in most cases by
the implementation of a posterior-only approach; however, the final treatment
should, when possible, include adjuvant chemotherapy and radiotherapy and
rigorous bracing.
PMID- 27507544
TI - Treatment of recalcitrant atrophic non-union of the humeral shaft with BMP-7,
autologous bone graft and hydroxyapatite pellets.
AB - Recalcitrant humeral non-union is a disabling condition that is extremely
difficult to treat. The use of BMP-7 has been proposed to improve bone healing.
This is a report of the results obtained in 12 patients with recalcitrant humeral
non-union treated using stable fixation with a long locking compression plate and
BMP-7, autologous bone graft and hydroxyapatite pellets applied at the non-union
site. Patients had up to three surgical attempts at non-union healing prior to
our treatment. The average time from the initial fracture to our surgery was 5.2
years. Average follow-up was 5.3 years. At follow-up, non-union had healed in all
patients by an average of 7.3 months. All the patients were very satisfied with
their final results, despite a restricted range of motion of the elbow and a
moderate muscular atrophy, which was frequently observed. Our study shows that
BMP-7 associated with autologous bone grafting and hydroxyapatite pellets after
stable fixation is an effective adjuvant to stimulate bone healing in the
treatment of recalcitrant humeral non-union.
PMID- 27507545
TI - Revision of ceramic fracture with ceramic-on-polyethylene in total hip
arthroplasty: Medium-term results.
AB - There is no consensus on the bearing of choice in revision for ceramic fracture
after total hip arthroplasty (THA). The aim of this study was to evaluate the
outcomes using ceramic-on-polyethylene (CoP) articulation in revision for ceramic
breakage. Twelve patients who underwent revision hip surgery between 2002 and
2013 were followed-up. Appropriate surgical technique, including accurate
synoviectomy, was used. The cup and the head were changed in four patients and
only the liner and the head were replaced in the remaining eight patients. At the
final follow-up there were no cases of re-revision due to tribological reasons,
and only one case of polyethylene (PE) wear and osteolysis was scheduled for a
new revision because of clear cup malposition. Complications were four cases of
dislocation, one case of loosening and one case of infection. Revision of
fractured ceramic is a challenging situation with a high risk of early
complications. Using CoP liners with accurate synoviectomy and correction of
misalignment can be considered a valuable bearing option at medium-term follow
up.
PMID- 27507546
TI - Long endomedullary nail in proximal third humeral shaft fractures.
AB - INTRODUCTION: Proximal humeral fractures with a spiral line of fracture extending
from the humeral head to the diaphyseal region are increasing. Treatment for
these fractures is comparable to that for shaft fractures. The purpose of this
study was to evaluate the use of a new "Long" humeral nail for this type of
lesion and identify the best distal locking. MATERIALS AND METHODS: Forty-three
patients treated with a Long Diphos Nail(r) were selected for this study: main
exclusion criteria were poor cognitive and responsive ability to physical
therapy, four-part fracture requiring humeral head replacement, an isolated
greater or lesser tubercle fracture and a head-splitting fracture. All patients
were divided into two groups according to the distal locking (single or double)
and clinically evaluated at 1, 3, 6 and 12 months after surgery. The following
parameters were evaluated: fracture healing on radiographic images every month;
level of pain with Visual Analogue Scale (VAS); recovery of shoulder function or
ability to resume normal daily activities according to the Constant Scoring
System (CSS); patient satisfaction; and complications, like fracture
consolidation defect or delay. A statistical analysis was performed. RESULTS:
Improvements in pain, satisfaction and shoulder functional recovery were
recorded. Patients reached fracture healing in two to six months. The mean
healing time was better for double distal locking (p=0.04).There was a clinically
greater difference (p=0.006) between the groups for the mean Constant score at 3
months follow-up, with better results for the double distal locking group.
Complications were: one patient with a consolidation delay with a single distal
locking screw breakage; it was necessary to remove the nail and perform a second
treatment. CONCLUSIONS: The results of the study indicate the efficacy of Long
Diphos Nail(r) in the treatment of fractures with a line of fracture extending to
the proximal diaphyseal region. The features of a multiplane stabilisation above
the fracture and a distal double locking may represent the key for a good
fixation for 11-A2, A3 or B2 fractures with a long spiral line. A double distal
locking reduces fracture micro-instability and so patients recover function and
strength quicker because of less pain at the fracture site. STUDY DESIGN:
retrospective, cohort of cases. LEVEL OF EVIDENCE: IV.
PMID- 27507547
TI - Outcomes and complications of triceps tendon repair following acute rupture in
American military personnel.
AB - INTRODUCTION: Triceps tendon ruptures are uncommon injuries primarily occurring
in young, active males or elderly individuals with various systemic diseases.
Relatively little is known about the epidemiology of this injury, or the results
of surgical management in high-demand populations. The purpose of this study was
to define the incidence and outcomes of surgical treatment in active duty
American military personnel. PATIENTS AND METHODS: The Military Data Repository
(MDR) was queried for all active duty military personnel undergoing surgical
repair or reconstruction of a triceps tendon rupture between January 2012 and
December 2014. The electronic health records of all patients with at least 12
months clinical follow-up were searched for demographic information, injury
details, preoperative imaging findings, post-operative complications, and ability
to return to duty following surgical repair. Incidence was calculated based on
total active duty population in the MDR over the study period. Risk factors for
postoperative complication and inability to return to duty following surgical
repair were assessed using univariate analyses. RESULTS: A total of 54 acute
triceps tendon ruptures were identified in the search, of which 48 had at least
12 months follow-up and complete post-operative records. The incidence of acute
triceps tendon rupture was 1.1 per 100,000 person-years. Twelve patients
experienced post-operative complications, six of which were traumatic re-ruptures
within four months of the index surgery. No patient had a post-operative
infection or atraumatic repair failure. 94% of patients were able to return to
active military service following surgical repair. Enlisted rank was a
significant risk factor for a post-operative complication, but no factor
predicted inability to return to active duty service. CONCLUSIONS: Surgical
repair of acute triceps tendon ruptures reliably restores strength and function
even in high-demand individuals. In our population, traumatic rerupture was the
most common complication.
PMID- 27507548
TI - Emergency Nurse Transport of Telemetry Patients: Benefits and Drawbacks.
AB - PROBLEM: Emergency nurse-accompanied telemetry transport on admission to the
hospital is a common practice. Potential drawbacks include inefficient use of
nursing resources, unnecessary telemetry transports, and disruption of care for
remaining ED patients. METHODS: This was a 2-part descriptive quality improvement
study using retrospective chart review and prospective documentation of patient
transports. Charts were selected by American Heart Association Practice Standards
for ECG Monitoring to classify transported telemetry patients into 3 categories.
Patient characteristics and adverse events were assessed. Prospectively, the
length of transport time and the number and severity of patients the transport
nurse left in the emergency department were also recorded. RESULTS: Zero adverse
events occurred during any transport. Transport time ranged from 5 to 38 minutes,
with a mean of 16.5 minutes. The normal patient ratio increased for nursing staff
remaining in the emergency department for the period of the transport, with 74%
of patients left in the emergency department classified into high-risk Emergency
Severity Index categories 1 and 2. IMPLICATIONS FOR PRACTICE: Findings provided
evidence that low-risk telemetry patients had minimal chance of adverse events
during transport and highlighted added risks for the remaining emergency
patients. Alternative models and interventions are needed to identify appropriate
patients for telemetry transport, assign appropriate staff such as licensed
paramedics for transport, and evaluate alternative models of nursing care and
teamwork in the emergency department.
PMID- 27507549
TI - What Qualitative Research Can Do for You: Deriving Solutions and Interventions
from Qualitative Findings.
PMID- 27507550
TI - Understanding the Experience of Miscarriage in the Emergency Department.
AB - INTRODUCTION: Up to 20% of pregnancies end in miscarriage, which can be a
significant life event for women with psychological implications. Because the
only preventative measure for a miscarriage is risk factor modification, the
treatment focuses on confirming the miscarriage has occurred and medical
management of symptoms. Although women experiencing a miscarriage are frequently
directed to seek medical care in emergency departments, the patients are often
triaged as nonemergent patients unless they are unstable, which exposes women to
potentially prolonged wait times. Research about miscarriages and emergency
departments predominantly focus on medical management with little understanding
of how emergency care shapes the experience of miscarriage for women. METHODS:
Seeking to describe the experiences of women coming to the emergency department
for care while having a miscarriage, interpretive phenomenology-a form of
qualitative research-guided this study. Eight women were recruited to participate
in semi-structured face-to-face interviews of 60 to 90 minutes in length. Data
were analyzed using hermeneutics and thematic analysis. RESULTS: Five themes
emerged: "Pregnant/Life: Miscarriage/Death"; "Deciding to go to the emergency
department: Something's wrong"; "Not an illness: A different kind of trauma";
"Need for acknowledgement"; and "Leaving the emergency department: What now?".
Participants believed their losses were not acknowledged but instead dismissed.
These experiences, combined with a perceived lack of discharge education and
clarity regarding follow-up, created experiences of marginalization. DISCUSSION:
This study describes the experience of miscarrying in emergency departments and
provides insights regarding how nursing and physician care may affect patient
perceptions of marginalization.
PMID- 27507551
TI - Materials in the vitreous demonstrated under the operating microscope during
cataract surgery and confirmed histologically.
PMID- 27507552
TI - Muscle expression of a malonyl-CoA-insensitive carnitine palmitoyltransferase-1
protects mice against high-fat/high-sucrose diet-induced insulin resistance.
AB - Impaired skeletal muscle mitochondrial fatty acid oxidation (mFAO) has been
implicated in the etiology of insulin resistance. Carnitine palmitoyltransferase
1 (CPT1) is a key regulatory enzyme of mFAO whose activity is inhibited by
malonyl-CoA, a lipogenic intermediate. Whereas increasing CPT1 activity in vitro
has been shown to exert a protective effect against lipid-induced insulin
resistance in skeletal muscle cells, only a few studies have addressed this issue
in vivo. We thus examined whether a direct modulation of muscle CPT1/malonyl-CoA
partnership is detrimental or beneficial for insulin sensitivity in the context
of diet-induced obesity. By using a Cre-LoxP recombination approach, we generated
mice with skeletal muscle-specific and inducible expression of a mutated CPT1
form (CPT1mt) that is active but insensitive to malonyl-CoA inhibition. When fed
control chow, homozygous CPT1mt transgenic (dbTg) mice exhibited decreased CPT1
sensitivity to malonyl-CoA inhibition in isolated muscle mitochondria, which was
sufficient to substantially increase ex vivo muscle mFAO capacity and whole body
fatty acid utilization in vivo. Moreover, dbTg mice were less prone to high
fat/high-sucrose (HFHS) diet-induced insulin resistance and muscle lipotoxicity
despite similar body weight gain, adiposity, and muscle malonyl-CoA content.
Interestingly, these CPT1mt-protective effects in dbTg-HFHS mice were associated
with preserved muscle insulin signaling, increased muscle glycogen content, and
upregulation of key genes involved in muscle glucose metabolism. These beneficial
effects of muscle CPT1mt expression suggest that a direct modulation of the
malonyl-CoA/CPT1 partnership in skeletal muscle could represent a potential
strategy to prevent obesity-induced insulin resistance.
PMID- 27507553
TI - Hepatic functions of GLP-1 and its based drugs: current disputes and
perspectives.
AB - GLP-1 and its based drugs possess extrapancreatic metabolic functions, including
that in the liver. These direct hepatic metabolic functions explain their
therapeutic efficiency for subjects with insulin resistance. The direct hepatic
functions could be mediated by previously assumed "degradation" products of GLP-1
without involving canonic GLP-1R. Although GLP-1 analogs were created as
therapeutic incretins, extrapancreatic functions of these drugs, as well as
native GLP-1, have been broadly recognized. Among them, the hepatic functions are
particularly important. Postprandial GLP-1 release contributes to insulin
secretion, which represses hepatic glucose production. This indirect effect of
GLP-1 is known as the gut-pancreas-liver axis. Great efforts have been made to
determine whether GLP-1 and its analogs possess direct metabolic effects on the
liver, as the determination of the existence of direct hepatic effects may
advance the therapeutic theory and clinical practice on subjects with insulin
resistance. Furthermore, recent investigations on the metabolic beneficial
effects of previously assumed "degradation" products of GLP-1 in the liver and
elsewhere, including GLP-128-36 and GLP-132-36, have drawn intensive attention.
Such investigations may further improve the development and the usage of GLP-1
based drugs. Here, we have reviewed the current advancement and the existing
controversies on the exploration of direct hepatic functions of GLP-1 and
presented our perspectives that the direct hepatic metabolic effects of GLP-1
could be a GLP-1 receptor-independent event involving Wnt signaling pathway
activation.
PMID- 27507554
TI - Restitution of Tumor Suppressor MicroRNA-145 Using Magnetic Nanoformulation for
Pancreatic Cancer Therapy.
AB - INTRODUCTION: The functional significance of lost microRNAs has been reported in
several human malignancies, including pancreatic cancer (PC). Our prior work has
identified microRNA-145 (miR-145) as a tumor suppressor microRNA (miRNA) in
pancreatic cancer. The restoration of miR-145 downregulates a number of oncogenes
including mucin MUC13, a transmembrane glycoprotein that is aberrantly expressed
in pancreatic cancer, thus efficiently inhibiting tumor growth in mice. However,
lack of an effective tumor-specific delivery system remains an unmet clinical
challenge for successful translation of microRNAs. METHODS: We developed a miRNA
145-based magnetic nanoparticle formulation (miR-145-MNPF) and assessed its anti
cancer efficacy. Physico-chemical characterization (dynamic light scattering
(DLS), transmission electron microscopy (TEM) and miR-binding efficiency),
cellular internalization (Prussian blue and confocal microscopy), miR-145
restitution potential (quantitative reverse-transcription PCR (qRT-PCR), and anti
cancer efficacy (proliferation, colony formation, cell migration, cell invasion
assays) of this formulation were performed using clinically relevant pancreatic
cancer cell lines (HPAF-II, AsPC-1). RESULTS: miR-145-MNPF exhibited optimal
particle size and zeta potential which effectively internalized and restituted
miR-145 in pancreatic cancer cells. miR-145 re-expression resulted in
downregulation of MUC13, HER2, pAKT, and inhibition of cell proliferation,
clonogenicity, migration, and invasion of pancreatic cancer cells. CONCLUSIONS:
miR-145-MNPF is an efficient system for miR-145 delivery and restitution in
pancreas cancer that may offer a potential therapeutic treatment for PC either
alone or in conjunction with conventional treatment.
PMID- 27507555
TI - Does Diverting Loop Ileostomy Improve Outcomes Following Open Ileo-Colic
Anastomoses? A Nationwide Analysis.
AB - BACKGROUND: Anastomotic leak is one of the most feared complications of
gastrointestinal surgery. Surgeons routinely perform a diverting loop ileostomy
(DLI) to protect high-risk colo-rectal anastomoses. STUDY DESIGN: The NSQIP
database was queried from 2012 to 2013 for patients undergoing open ileo-colic
resection with and without a DLI. The primary outcome was the development of any
anastomotic leak-including those managed operatively and non-operatively.
Secondary outcomes included overall complication rate, return to the OR,
readmission, and 30-day mortality. RESULTS: Four thousand one hundred fifty-nine
patients underwent open ileo-colic resection during the study period. One hundred
eighty-six (4.5 %) underwent a DLI. Factors associated with the addition of a DLI
included emergency surgery, pre-operative sepsis, and IBD. There were 197
anastomotic leaks (4.7 %) with 100 patients requiring reoperation (2.4 %). DLI
was associated with a decrease in anastomotic leaks requiring reoperation (DLI vs
no DLI: 0 (0 %) vs 100 (2.5 %); p = 0.02) and with increased readmission (OR
1.93; 95 % CI 1.30-2.85; p = 0.001). CONCLUSION: DLI is rarely used for open ileo
colic resection. There were no serious leaks requiring reoperation in the DLI
group. A DLI was associated with an almost two-fold increase in the odds of
readmission. Surgeons must weigh the reduction in serious leak rate with
postoperative morbidity when considering a DLI for open ileo-colic resection.
PMID- 27507556
TI - IL-33 inhibits the differentiation and immunosuppressive activity of granulocytic
myeloid-derived suppressor cells in tumor-bearing mice.
AB - Myeloid-derived suppressor cells (MDSCs) contribute to tumor-mediated immune
escape by suppressing antitumor immune responses. Interleukin-33 (IL-33) is
capable of regulating various immune cell populations; however, the effects of IL
33 on the differentiation of MDSCs have not been well characterized. In this
study, we evaluated the effects of IL-33 on MDSCs and found that IL-33
significantly reduced the differentiation of lineage-negative bone marrow
progenitor cells into granulocytic MDSCs (G-MDSCs). IL-33-treated MDSCs exhibited
diminished immunosuppressive capacity; reduced inhibition on T-cell proliferation
and interferon-gamma production, and diminished production of reactive oxygen
species. However, IL-33 treatment did not affect the frequency of monocytic MDSCs
(M-MDSCs) or their production of nitric oxide and expression of arginase-1.
Additionally, compared with control MDSCs, IL-33-treated MDSCs had reduced
capacity to induce the differentiation or expansion of Treg cells. Moreover, in
vivo IL-33 administration significantly decreased MDSCs and G-MDSCs accumulation
in the spleen and tumor microenvironment. Also, despite increasing CD4+ and CD8+
T-cell infiltration, IL-33 administration markedly decreased Treg-cell population
in tumor microenvironment. Taken together, our findings indicate that IL-33
reduces the frequency and immunosuppressive activity of G-MDSCs and ultimately
the extent of tumor growth.
PMID- 27507558
TI - Long-term result of autologous cultivated oral mucosal epithelial transplantation
for severe ocular surface disease.
AB - The present study aimed to investigate the clinical outcomes of autologous
cultivated oral mucosal epithelial transplantation (COMET) on human amniotic
membrane (AM) for corneal limbal stem cell deficiency (LSCD). In this
prospective, noncomparative case series, 20 eyes (18 patients) with bilateral
severe ocular surface disease were chosen to undergo COMET on human AM. The
primary outcome was clinical success, and the secondary outcomes were the best
corrected visual acuity difference, corneal opacification, symblepharon
formation, and complications. The mean patient age was 48.2 +/- 15.5 years. The
mean follow-up time was 31.9 +/- 12.1 months (range 8-50 months). All except one
eye exhibited complete epithelialization within the first postoperative week. A
successful clinical outcome, defined as a stable ocular surface without
epithelial defects, a clear cornea without fibrovascular tissue invasion at the
pupillary area, and no or mild ocular surface inflammation, was obtained in 15 of
20 eyes (75 %). The clinical success rate at 1 year was 79.3 %, and that at 4
years (end of follow-up) was 70.5 %. Fourteen of 20 (70 %) eyes exhibited
improvement in visual acuity after COMET, and some required subsequent cataract
surgery (2 eyes), penetrating keratoplasty (3 eyes), or keratoprosthesis
implantation (1 eye). Preoperative symblepharon was eliminated in most eyes (8 of
13, 61.5 %) after COMET combined with eyelid reconstruction when needed. The only
complication was corneal perforation (1 eye) induced by a severe eyelid
abnormality; treatment with a tectonic corneal graft was successful. COMET can
successfully restore ocular surface damage in most eyes with corneal LSCD.
PMID- 27507557
TI - Maintenance of the EBV-specific CD8+ TCRalphabeta repertoire in immunosuppressed
lung transplant recipients.
AB - Epstein-Barr virus (EBV) is one of the most common viruses in humans, capable of
causing life-threatening infections and cancers in immunocompromised individuals.
Although CD8+ T cells provide key protection against EBV, the persistence and
dynamics of specific T-cell receptor (TCR) clones during immunosuppression in
transplant patients is largely unknown. For the first time, we used a novel
single-cell TCRalphabeta multiplex-nested reverse transcriptase PCR to dissect
TCRalphabeta clonal diversity within GLCTLVAML (GLC)-specific CD8+ T cells in
healthy individuals and immunocompromised lung transplant recipients. The GLC
peptide presented by HLA-A*02:01 is one of the most immunogenic T-cell targets
from the EBV proteome. We found that the GLC-specific TCRalphabeta repertoire was
heavily biased toward TRAV5 and encompassed five classes of public TCRalphabetas,
suggesting that these clonotypes are preferentially utilized following infection.
We identified that a common TRAV5 was diversely paired with different TRAJ and
TRBV/TRBJ genes, in both immunocompetent and immunocompromised individuals, with
an average of 12 different TCRalphabeta clonotypes/donor. Moreover, pre
transplant GLC-specific TCRalphabeta repertoires were relatively stable over 1
year post transplant under immunosuppression in the absence or presence of EBV
reactivation. In addition, we provide the first evidence of early GLC-specific
CD8+ T cells at 87 days post transplant, which preceded clinical EBV detection at
242 days in an EBV-seronegative patient receiving a lung allograft from an EBV
seropositive donor. This was associated with a relatively stable TCRalphabeta
repertoire after CD8+ T-cell expansion. Our findings provide insights into the
composition and temporal dynamics of the EBV-specific TCRalphabeta repertoire in
immunocompromised transplant patients and suggest that the early detection of EBV
specific T cells might be a predictor of ensuing EBV blood viremia.
PMID- 27507559
TI - The increased level of COX-dependent arachidonic acid metabolism in blood
platelets from secondary progressive multiple sclerosis patients.
AB - Platelet activation is increasingly postulated as a possible component of the
pathogenesis of multiple sclerosis (MS), especially due to the increased risk of
cardiovascular events in MS. Arachidonic acid cascade metabolized by
cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our
study was to investigate the COX-dependent arachidonic acid metabolic pathway in
blood platelets from secondary progressive multiple sclerosis (SP MS) patients.
The blood samples were obtained from 50 patients (man n = 22; female n = 28),
suffering from SP MS, diagnosed according to the revised McDonald criteria.
Platelet aggregation was measured in platelet-rich plasma after arachidonic acid
stimulation. The level of COX activity and thromboxane B2 concentration were
determined by ELISA method. Lipid peroxidation was assessed by measuring the
level of malondialdehyde. The results were compared with a control group of
healthy volunteers. We found that blood platelets obtained from SP MS patients
were more sensitive to arachidonic acid and their response measured as platelet
aggregation was stronger (about 14 %) relative to control. We also observed a
significantly increased activity of COX (about 40 %) and synthesis of thromboxane
B2 (about 113 %). The generation of malondialdehyde as a marker of lipid
peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase
dependent arachidonic acid metabolism is significantly increased in blood
platelets of patients with SP MS. Future clinical studies are required to
recommend the use of low-dose aspirin, and possibly other COX inhibitors in the
prevention of cardiovascular risk in MS.
PMID- 27507561
TI - Prevalence and intensity of Streblidae in bats from a Neotropical savanna region
in Brazil.
AB - Bats of the family Phyllostomidae are common hosts to streblids known as bat
flies. Here, we discuss the component community, prevalence and intensity of
infection with species of Streblidae on an assemblage of phyllostomid bats in the
Cafuringa Environmental Protection Area (APA Cafuringa) in the core area of the
Cerrado in Central Brazil. A total of 1 841 streblid individuals of 24 species
occurred on 752 bats of 14 species. Ten species of streblids infected Glossophaga
soricina (Pallas), whereas seven or fewer streblid species infected the other bat
species. Nine bat fly species presented a prevalence of more than 50%, whereas
some differences in the abundance of bat flies among hosts were observed. Strebla
wiedemanni Kolenati, 1856 and Trichobius furmani Wenzel, 1966 were more host
specific compared to the other streblids, and they occurred in greater abundance
on their preferred hosts. Trichobius uniformis Curran, 1935 and Strebla mirabilis
(Waterhouse, 1879) were the least host-specific, occurring on five and six hosts,
respectively.
PMID- 27507560
TI - Trends and area variations in Potentially Preventable Admissions for COPD in
Spain (2002-2013): a significant decline and convergence between areas.
AB - BACKGROUND: Potentially Preventable Hospitalizations (PPH) are hospital
admissions for conditions which are preventable with timely and appropriate
outpatient care being Chronic Obstructive Pulmonary Disease (COPD) admissions one
of the most relevant PPH. We estimate the population age-sex standardized
relative risk of admission for COPD-PPH by year and area of residence in the
Spanish National Health System (sNHS) during the period 2002-2013. METHODS: The
study was conducted in the 203 Hospital Service Areas of the sNHS, using the 2002
to 2013 hospital admissions for a COPD-PPH condition of patients aged 20 and
over. We use conventional small area variation statistics and a Bayesian
hierarchical approach to model the different risk structures of dependence in
both space and time. RESULTS: COPD-PPH admissions declined from 24.5 to 15.5 per
10,000 persons-year (Men: from 40.6 to 25.1; Women: from 9.1 to 6.4). The
relative risk declined from 1.19 (19 % above 2002-2013 average) in 2002 to 0.77
(30 % below average) in 2013. Both the starting point and the slope were
different for the different regions. Variation among admission rates between
extreme areas dropped from 6.7 times higher in 2002 to 4.6 times higher in 2013.
CONCLUSIONS: COPD-PPH conditions in Spain have undergone a strong decline and a
reduction in geographical variation in the last 12 years, suggesting a general
improvement in health policies and health care over time. Variability among areas
still remains, with a substantial room for improvement.
PMID- 27507562
TI - Combination of phosphotidylinositol-3-kinase targeting with cetuximab and
irradiation: A preclinical study on an orthotopic xenograft model of head and
neck cancer.
AB - BACKGROUND: The purpose of this study was to investigate the effects of combining
the phosphotidylinositol-3-kinase (PI3K) inhibitor buparlisib (BKM)120 with the
anti-epidermal growth factor receptor (EGFR) agent cetuximab and radiotherapy
(RT) on an orthotopic model of head and neck squamous cell carcinoma (HNSCC).
METHODS: We evaluated the antitumor efficacy of BKM120, cetuximab, and RT,
administered alone or in combination, using the human PIK3CA-mutated HNSCC cell
line, CAL33, injected into the floor of the mouth of nude mice. RESULTS: Compared
with control, the BKM120-cetuximab and the BKM120-cetuximab-RT combinations led
to the highest tumor inhibition (p < .001). The highest inhibitory effect of
treatments on cell proliferation, mitogen-activated protein kinase (MAPK) and
PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling
pathways were found with the BKM120-cetuximab association. The association of
BKM120 and cetuximab with RT inhibited RT-induced activation of the MAPK pathway.
CONCLUSION: These results can serve as a preclinical rationale for innovative
treatments combining PI3K inhibition with anti-EGFR therapies and irradiation in
patients with HNSCC. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 151-159,
2017.
PMID- 27507563
TI - The Importance of Debiasing Social Media Data to Better Understand E-Cigarette
Related Attitudes and Behaviors.
PMID- 27507564
TI - Social Contact and Cognitive Functioning: The Role of Personality.
AB - Objectives: Social contact has been shown to be positively associated with
cognitive functioning. It is unclear, however, whether all individuals can
equally benefit from social contact with regard to their cognitive functioning.
The goal of this study was to examine whether the beneficial effects of social
contact are affected by individual differences in personality. Method: We
examined the Big Five personality traits as moderators of the associations
between social contact and episodic memory and executive functioning using the
second wave of the Midlife in the U.S. study (N = 3,524, M(age) = 55.8). Results:
High levels of Extraversion and low levels of Openness to Experience strengthened
the association between social contact and memory and executive functioning. High
levels of Neuroticism and Agreeableness weakened the association of social
contact with memory but not with executive functioning. The results are
consistent across adulthood. Discussion: Personality modifies the social contact
cognition association. Whereas extraverts may need social contact for cognitive
stimulation, those who are high on Openness gain their stimulations elsewhere.
The highly neurotic might experience contact as stressful and hence as less
beneficial. Emotional rather than cognitive motivation might be the reason that
the highly agreeable benefit less from social contact with regard to their
cognitive functioning.
PMID- 27507565
TI - The Associations Between Dispositional Mindfulness, Sense of Control, and Affect
in a National Sample of Adults.
AB - Objectives: The present study examined factors associated with better affective
experiences across the life span, extending existing research to older adults.
Specifically, we investigated dispositional mindfulness and sense of control as
predictors of affect and sense of control as a potential mediator of the
mindfulness-affect associations. Method: We hypothesized that dispositional
mindfulness mediated by sense of control would predict affective outcomes. An
archival analysis of a sample of 4,962 adults, aged 28 to 84 years, was conducted
using the Midlife in the U.S. national survey (MIDUS-II). Exploratory analyses
were conducted with age as a moderator in all associations. Results: Greater
dispositional mindfulness predicted more positive and negative affect
irrespective of age. Dispositional mindfulness did not predict sense of control.
Greater sense of control predicted more positive and less negative affect, and
these associations were significantly moderated by age. Sense of control did not
mediate the dispositional mindfulness-affect associations. Discussion: The
present study extends existing research on the dispositional mindfulness-positive
affect association to older ages. The sense of control and positive and negative
affect associations are enhanced and buffered, respectively, at older ages,
indicating that the association between control and affect differs by age.
PMID- 27507566
TI - Missing the mark: ongoing missed opportunities for HIV diagnosis at an urban
medical center despite universal screening recommendations.
AB - BACKGROUND: Despite established recommendations from the Centers for Disease
Control (CDC) to scale up testing efforts in the USA, this study shows full scale
implementation of these recommendations may still be lacking. We hypothesize that
patients experience ongoing missed opportunities for earlier diagnosis of HIV,
despite frequent encounters to Montefiore Medical Center (MMC), an integrated
hospital system in the Bronx, NY. METHODS: Retrospective chart review via
electronic medical records of patients newly diagnosed with HIV in 2012 and 2013
at varied MMC clinical sites. Missed opportunities were defined as > 1 prior
health care encounter at MMC within three calendar years of diagnosis, in which
HIV testing was not offered for those who had a prior negative test or no prior
test. RESULTS: There were 218 patients newly diagnosed with HIV at MMC during the
study period; 31% presented with a CD4 <200 cells/mm3; 22% were asymptomatic at
diagnosis. Patients (56%) without a prior HIV test had an average 4.72 clinical
encounters at MMC within the 3 years prior to their HIV diagnosis. Over 95% of
visits prior to diagnosis occurred in emergency departments (EDs) or primary care
outpatient department (OPDs) and accounted for the vast majority of missed
opportunities. CONCLUSIONS: HIV infected patients continue to present late to
care, with low CD4 and commonly utilize OPDs and EDs, where missed opportunities
for earlier diagnosis are common. Practices that address augmentation of current
HIV testing strategies are needed, especially in outpatient and first-contact
acute care settings.
PMID- 27507567
TI - Screening the low molecular weight fraction of human serum using ATR-IR
spectroscopy.
AB - Vibrational spectroscopic techniques can detect small variations in molecular
content, linked with disease, showing promise for screening and early diagnosis.
Biological fluids, particularly blood serum, are potentially valuable for
diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains
the associated peptidome and metabolome and has been identified as potentially
the most relevant molecular population for disease-associated biomarker research.
Although vibrational spectroscopy can deliver a specific chemical fingerprint of
the samples, the High Molecular Weight Fraction (HMWF), composed of the most
abundant serum proteins, strongly dominates the response and ultimately makes the
detection of minor spectral variations a challenging task. Spectroscopic
detection of potential serum biomarkers present at relatively low concentrations
can be improved using pre-analytical depletion of the HMWF. In the present study,
human serum fractionation by centrifugal filtration was used prior to analysis by
Attenuated Total Reflection infrared spectroscopy. Using a model sample based on
glycine spiked serum, it is demonstrated that the screening of the LMWF can be
applied to quantify blinded concentrations up to 50 times lower. Moreover, the
approach is easily transferable to different bodily fluids which would support
the development of more efficient and suitable clinical protocols exploring
vibrational spectroscopy based ex-vivo diagnostic tools. Revealing serum LMWF for
spectral serological diagnostic applications.
PMID- 27507568
TI - Risk factors for choroidal detachment following rhegmatogenous retinal detachment
in a chinese population.
AB - BACKGROUD: Choroidal detachment (CD) following primary rhegmatogenous retinal
detachment (RRD) is a special type of RRD. The purpose of this study is to
investigate the potential risk factors of RRD with CD in a Chinese population.
METHODS: All of 201 consecutive RRD with CD patients and 210 RRD without CD
patients were enrolled in this case-control retrospective study. The clinical
data from these cases were reviewed here. Patients were undergone scleral
buckling or encircling or both, or pars plana vitrectomy with or without scleral
buckling or encircling or both according the patients' condition. The incidence
of RRD with CD in this Chinese population was measured, and the potential risk
factors for the development of RRD with CD were investigated by multivariate
logistic regression analysis. RESULTS: In this population, the incidence of RRD
with CD was 8.6 %. The incidence of RRD with CD was significantly higher in
patients with macular hole (P < 0.05), retinal breaks located posterior to the
equator (P < 0.05), and total detachment (P < 0.05). Furthermore, the incidence
of RRD with CD was significantly higher in patients with longer axial length (P <
0.05) only when ages, IOP, AL and duration time was set for categorical
variables. CONCLUSIONS: Hypotony, retinal breaks located posteriorly especially
macular hole, longer axial length, and the whole retinal detachment might be the
potential risk factors for the development of CD in RRD patients.
PMID- 27507569
TI - User involvement in the implementation of clinical guidelines for common mental
health disorders: a review and compilation of strategies and resources.
AB - BACKGROUND: There is now broad consensus regarding the importance of involving
users in the process of implementing guidelines. Few studies, however, have
addressed this issue, let alone the implementation of guidelines for common
mental health disorders. The aim of this study is to compile and describe
implementation strategies and resources related to common clinical mental health
disorders targeted at service users. METHODS: The literature was reviewed and
resources for the implementation of clinical guidelines were compiled using the
PRISMA model. A mixed qualitative and quantitative analysis was performed based
on a series of categories developed ad hoc. RESULTS: A total of 263 items were
included in the preliminary analysis and 64 implementation resources aimed at
users were analysed in depth. A wide variety of types, sources and formats were
identified, including guides (40%), websites (29%), videos and leaflets, as well
as instruments for the implementation of strategies regarding information and
education (64%), self-care, or users' assessment of service quality. CONCLUSIONS:
The results reveal the need to establish clear criteria for assessing the quality
of implementation materials in general and standardising systems to classify user
targeted strategies. The compilation and description of key elements of
strategies and resources for users can be of interest in designing materials and
specific actions for this target audience, as well as improving the
implementation of clinical guidelines.
PMID- 27507570
TI - Antenatal immunoglobulin for prevention of neonatal hemochromatosis.
AB - Neonatal hemochromatosis (NH) is a rare disease with a poor prognosis,
particularly prior to 2008. Antenatal maternal high-dose immunoglobulin (Ig) is
effective in preventing NH recurrence, but the adverse effects of this treatment
have not been documented as yet. Here, we report on a patient who underwent high
dose Ig treatment to prevent NH recurrence. The patient was a 31-year-old
pregnant Japanese woman. Her first child died of NH after receiving living donor
liver transplantation. The patient received high-dose Ig treatment to prevent
recurrence of NH from gestational weeks 16 to 35. During the treatment, platelet
count gradually decreased, and cesarean section was required at 35 gestational
weeks. The child did not develop liver failure. High-dose Ig prevented the
recurrence of NH. Caution should be exercised due to possible adverse effects of
this treatment.
PMID- 27507572
TI - A dose-response estimate for acute alcohol use and risk of suicide attempt.
AB - This study reports dose-response estimates for the relative risk and population
attributable risk (PAR) between acute alcohol use and serious suicide attempt.
Data were analyzed on 272 suicide attempters arriving at 38 emergency departments
within 6 hours of the event in 17 countries. Case-crossover analysis, pair
matching the number of standard drinks consumed within the 6 hours prior to the
suicide attempt with that consumed during the same 6-hour period of the previous
week, was performed using fractional polynomial analysis for dose-response. Every
drink increased the risk of a suicide attempt by 30 percent; even one-two drinks
was associated with a sizable increase in the risk of a serious suicide attempt,
and a dose-response was found for the relationship between drinking 6 hours prior
and the risk of a suicide attempt up to 20 drinks. Acute use of alcohol was
responsible for 35 percent PAR of all suicide attempts. While very high levels of
drinking were associated with larger relative risk s of suicide attempt, the
control and reduction of smaller quantities of acute alcohol use also had an
impact on population levels of suicide attempt, as showed here for the first time
with our PAR estimates. Interventions to stop drinking or at least decrease
levels of consumption could reduce the risk of suicide attempt. Screening people
more at risk to suffer these acute effects of ethanol and offering interventions
that work to these high-risk groups are a matter of urgent new research in the
area.
PMID- 27507573
TI - Thrombotic mass traversing a patent foramen ovale.
PMID- 27507574
TI - Iodine 125 Seed for Localization in Primary Hyperparathyroidism.
AB - Background Preoperative localization of the parathyroid gland prior to a
minimally invasive parathyroidectomy (MIP) is important because of varying
locations of the parathyroid gland. Several methods have been described to
localize the affected gland. One novel technique is the use of an iodine 125 (I
125) seed as a marker. The aim of this study is to evaluate the feasibility of
using an I-125 seed in localizing the diseased parathyroid gland prior to MIP.
Materials and methods This is a pilot study of 10 patients performed in the
Amphia Hospital, the Netherlands. Patients in whom primary hyperparathyroidism
(PHPT) was diagnosed in combination with 1 enlarged parathyroid gland on
ultrasound (US) and scintigraphy and who were eligible for MIP were included in
this study. These patients underwent a preoperative US-guided I-125 seed
placement in the affected parathyroid gland. The main study parameters were the
feasibility of the placement, intraoperative localization of the diseased gland
and complications. Results A total of 10 patients were included. The US-guided I
125 placement in the affected parathyroid gland was technically feasible in the
majority of cases. Because of the anatomical location of the gland, the placement
was difficult in 2 patients, resulting in suboptimal position and possible
misplacement of the marker. MIP was uncomplicated in most cases. Complications
during surgery were mainly intraoperative bleeding. Conclusions The use of an I
125 seed for preoperative localization in PHPT is a relatively safe technique in
parathyroid surgery. More research is needed to compare this technique with other
preoperative localization techniques.
PMID- 27507575
TI - Variation and Acquisition of Complex Techniques: Pancreaticoduodenectomy.
AB - Background Complex procedures often have numerous acceptable approaches; it is
unclear how surgical fellows choose between techniques. We used
pancreaticoduodenectomy as a model to catalogue variability between surgeons and
investigate factors that affect fellows' acquisition of techniques. Materials and
methods Semistructured interviews and operative note analysis were conducted to
determine techniques of 5 attending surgeons, and these data were mapped to
identify variations. Identical interviews and questioning were completed with 4
fellowship graduates whose practice includes pancreaticoduodenectomy. Results All
surgeons performed a different operation, both in order and techniques employed.
Based on minor variations, there were 21 surgical step data points that differed.
Of 5 surgeons, 4 were unable to identify colleagues' techniques. Fellows reported
adopting techniques from mentors who had regimented techniques, teaching styles
they related to, and with whom they frequently operated. Residency training did
not strongly influence their choice of technique; however, senior partners after
fellowship did influence technique. Conclusions The number of variants of
pancreaticoduodenectomy based on granular, step-by-step differences is larger
than previously described. Results hint that variation may be furthered by the
fact that surgeons are not aware of the techniques used by colleagues. Fellows
choose techniques based on factors not directly related to their own outcomes but
rather mentor factors. Whether fellows adopt techniques that will be optimal
given their abilities is worthy of further investigation, as are changes in
technique over time. Better codification of variation is needed to facilitate
these investigations as well as matching of technical variations to patient
outcomes.
PMID- 27507576
TI - [Possibilities, limitations, and perspectives in diagnosis and treatment of
glaucoma : Tried and tested procedures in a new light].
PMID- 27507577
TI - Revealing complex function, process and pathway interactions with high-throughput
expression and biological annotation data.
AB - The biological relationships both between and within the functions, processes and
pathways that operate within complex biological systems are only poorly
characterized, making the interpretation of large scale gene expression datasets
extremely challenging. Here, we present an approach that integrates gene
expression and biological annotation data to identify and describe the
interactions between biological functions, processes and pathways that govern a
phenotype of interest. The product is a global, interconnected network, not of
genes but of functions, processes and pathways, that represents the biological
relationships within the system. We validated our approach on two high-throughput
expression datasets describing organismal and organ development. Our findings are
well supported by the available literature, confirming that developmental
processes and apoptosis play key roles in cell differentiation. Furthermore, our
results suggest that processes related to pluripotency and lineage commitment,
which are known to be critical for development, interact mainly indirectly,
through genes implicated in more general biological processes. Moreover, we
provide evidence that supports the relevance of cell spatial organization in the
developing liver for proper liver function. Our strategy can be viewed as an
abstraction that is useful to interpret high-throughput data and devise further
experiments.
PMID- 27507579
TI - Reduced saccadic inhibition of return to moving eyes in autism spectrum
disorders.
AB - Inhibition of Return (IOR) refers to slower reaction time to a target presented
at the same location as a preceding stimulus. Here, we examine reflexive
attention orienting via the saccadic IOR using a shift in gaze direction (i.e.
from averted to direct) in faces presented as a peripheral cue, in upright and
inverted orientations, in adults with Autism Spectrum Disorder (ASD) and
typically developed comparison participants. While both groups showed an IOR in
the inverted face condition, this effect was reduced in participants with ASD in
the upright face condition, as compared to comparison participants, suggesting
that moving eyes do not trigger reflexive exogenous orienting in individuals with
ASD. Impaired reflexive orienting to eye gaze might severely compromise the later
development of social functions in ASD, such as joint attention, face emotion
recognition and mindreading.
PMID- 27507578
TI - HNO suppresses LPS-induced inflammation in BV-2 microglial cells via inhibition
of NF-kappaB and p38 MAPK pathways.
AB - Both hydrogen sulfide (H2S) and nitric oxide (NO) are important gaseous
mediators. We and others previously reported that these two gases react with each
other to generate a new mediator, nitroxyl (HNO), and regulate cardiovascular
functions. In this study, we demonstrated for the first time that the interaction
between the two gases also existed in microglia. The biological functions of HNO
in microglial cells were further studied with Angeli's salt (AS), an HNO donor.
We found that AS attenuated lipopolysaccharide (LPS)-evoked production of
reactive oxygen species (ROS) and pro-inflammatory cytokines (e.g. IL-1beta and
TNFalpha) through downregulating the expression of inducible nitric oxide
synthase (iNOS) and cyclooxygenase-2 (COX-2). HNO significantly reduced the
phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the activation
of nuclear factor-kappaB (NF-kappaB) through suppression of phosphorylation p65
and IkappaBalpha. The above effects were abolished by l-cysteine, an HNO
scavenger, but were not mimicked by nitrite, another product of AS during
generating HNO. A Cys-179-to-Ala mutation in inhibitory kappaB kinase beta
(IKKbeta) mimicked the effect of HNO on LPS-induced NF-kappaB activation.
Interestingly, AS abolished the inflammation in cells overexpressing WT-IKKbeta,
but had no significant effect in cells overexpressing C179A-IKKbeta. These data
suggest that HNO may act on C179 to prevent IKKbeta-dependent inflammation. Taken
together, our data demonstrated for the first time that H2S interacts with NO to
generate HNO in microglial cells. HNO produces anti-inflammatory effects through
suppressing the IKKbeta dependent NF-kappaB activation and p38 MAPK pathways.
PMID- 27507580
TI - Outlining face processing skills of portrait artists: Perceptual experience with
faces predicts performance.
AB - Most humans seem to demonstrate astonishingly high levels of skill in face
processing if one considers the sophisticated level of fine-tuned discrimination
that face recognition requires. However, numerous studies now indicate that the
ability to process faces is not as fundamental as once thought and that
performance can range from despairingly poor to extraordinarily high across
people. Here we studied people who are super specialists of faces, namely
portrait artists, to examine how their specific visual experience with faces
relates to a range of face processing skills (perceptual discrimination, short-
and longer term recognition). Artists show better perceptual discrimination and,
to some extent, recognition of newly learned faces than controls. They are also
more accurate on other perceptual tasks (i.e., involving non-face stimuli or
mental rotation). By contrast, artists do not display an advantage compared to
controls on longer term face recognition (i.e., famous faces) nor on person
recognition from other sensorial modalities (i.e., voices). Finally, the face
inversion effect exists in artists and controls and is not modulated by artistic
practice. Advantages in face processing for artists thus seem to closely mirror
perceptual and visual short term memory skills involved in portraiture.
PMID- 27507581
TI - Southward autumn migration of waterfowl facilitates cross-continental
transmission of the highly pathogenic avian influenza H5N1 virus.
AB - The highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide
zoonotic infectious disease, threatening humans, poultry and wild birds. The role
of wild birds in the spread of HPAI H5N1 has previously been investigated by
comparing disease spread patterns with bird migration routes. However, the
different roles that the southward autumn and northward spring migration might
play in virus transmission have hardly been explored. Using direction analysis,
we analyze HPAI H5N1 transmission directions and angular concentration of
currently circulating viral clades, and compare these with waterfowl seasonal
migration directions along major waterfowl flyways. Out of 22 HPAI H5N1
transmission directions, 18 had both a southward direction and a relatively high
concentration. Differences between disease transmission and waterfowl migration
directions were significantly smaller for autumn than for spring migration. The
four northward transmission directions were found along Asian flyways, where the
initial epicenter of the virus was located. We suggest waterfowl first picked up
the virus from East Asia, then brought it to the north via spring migration, and
then spread it to other parts of world mainly by autumn migration. We emphasize
waterfowl autumn migration plays a relatively important role in HPAI H5N1
transmission compared to spring migration.
PMID- 27507582
TI - Transversus abdominis plane block or intravenous lignocaine in open prostate
surgery: a randomized controlled trial.
AB - BACKGROUND AND OBJECTIVES: Transversus abdominis plane block (TAP) and
intravenous lignocaine are two analgesic techniques frequently used after
abdominal surgery. We hypothesized that these two techniques improve post
operative analgesia after open prostate surgery and sought to compare their
efficacy on immediate post-operative outcome after open prostate surgery.
METHODS: After ethics committee approval, 101 patients were enrolled in this
prospective study and randomly allocated to receive bilateral ultrasound-guided
TAP (n = 34), intravenous lignocaine (n = 33) or placebo (n = 34). In addition,
intravenous paracetamol was given every 6 h. The primary endpoint was the
cumulative opioid consumption during the first 48 post-operative hours
(median[IQR]). Secondary endpoints included pain scores at rest and upon
coughing, need for rescue tramadol, incidence of post-operative nausea and
vomiting (PONV), recovery of bowel function and incidence of bladder catheter
related discomfort. RESULTS: Cumulative piritramide consumption after 48 h was 28
[23] mg in the control group, 21 [29] mg in the TAP group and 21 [31] mg in the
lignocaine group (P = 0.065). There was no significant difference in post
operative pain scores between groups. The proportions of patients requiring
rescue tramadol, experiencing PONV or bladder catheter-related discomfort were
similar in each group. Recovery of bowel function was also similar in the three
groups. CONCLUSIONS: Our study suggests that TAP block and intravenous lignocaine
do not improve the post-operative analgesia provided by systematic administration
of paracetamol after open prostatectomy.
PMID- 27507583
TI - Rh-Catalyzed annulations of N-methoxybenzamides with ketenimines: synthesis of 3
aminoisoindolinones and 3-diarylmethyleneisoindolinones with strong aggregation
induced emission properties.
AB - Rhodium-catalyzed C-H activation/annulation reactions of ketenimines with N
methoxybenzamides furnished 3-aminoisoindolin-1-ones and 3
(diarylmethylene)isoindolin-1-ones. The synthesized 3-(diarylmethylene)isoindolin
1-ones exhibited aggregation induced emissions in aqueous tetrahydrofuran
solution and strong green-yellow emissions in solids.
PMID- 27507584
TI - Alterations of Glycosphingolipids in Embryonic Stem Cell Differentiation and
Development of Glycan-Targeting Cancer Immunotherapy.
AB - All mammalian cells display an array of surface glycans that can modulate
cellular interactions and regulate the development of an organism. In spite of
their important implications in health and disease, investigations of glycans
pose a great challenge given their inherent heterogeneity and the frequently
observed cross-reactivities of antibodies against glycosphingolipids (GSLs) with
multiple glycans, which may lead to erroneous interpretation and conclusion. We
employed matrix-assisted laser desorption-ionization mass spectrometry and tandem
MS/MS analyses to systematically delineate changes in GSLs during differentiation
of human embryonic stem (ES) and induced pluripotent stem cells into various
derivatives. In addition to the well-known human ES-specific markers, stage
specific embryonic antigen (SSEA)-3 and SSEA-4 and several globo- and lacto
series GSLs (Gb4Cer, Lc4Cer, fucosyl-Lc4Cer, Globo H, and disialyl-Gb5Cer) not
reported previously were identified. A close association of the switching of core
structures of GSLs from globo- and lacto- to ganglio-series during ES
differentiation was revealed, consistent with the observed changes in GSL
expression during murine embryonic development. Such switching was accompanied
with the concerted changes in the expression of glycosyltransferases during
differentiation. Finally, since aberrant glycosylation is a general feature of
cancer, targeting tumor-associated surface glycans for cancer immunotherapy is
gaining international attention. While GD2-targeted immunotherapy of
neuroblastoma represents the first antiglycan monoclonal antibody to obtain FDA
approval for standard medical care, Globo H-targeted immunotherapy of breast
cancer has generated promising results in the ongoing multinational clinical
trials. In this study, we also describe the studies of the scientific rationales
for the use of glycans as anticancer immunotherapeutics.
PMID- 27507585
TI - Successful management of apical abscess after Nipro left ventricular assisted
device explantation by removal of apical cuff and omentopexy.
AB - Nipro-Toyobo-paracorporeal pulsatile flow VAD (Nipro VAD; Nipro, Osaka, Japan)
has been used most commonly as a paracorporeal VAD (p-VAD) in Japan. There are
few reports describing clinical course of post LVAD explantation and its
complication. We herein present two cases of apical abscess after the
explantation of the device. SSI is a main risk factor of formation of the apical
abscess at the time of LVAD explantation. It is mandatory to perform sufficient
debridement and closure of the layers including abdominal muscle and anterior
abdominal fascia at exit sites in the explantation surgery. Omentopexy is also
helpful for prevention from infection. Routine removal of apical cuff and outflow
graft could be considered as one of the options when LVAD is explanted as bridge
to recovery.
PMID- 27507586
TI - Infection control in healthcare settings: perspectives for mfDNA analysis in
monitoring sanitation procedures.
AB - BACKGROUND: Appropriate sanitation procedures and monitoring of their actual
efficacy represent critical points for improving hygiene and reducing the risk of
healthcare-associated infections. Presently, surveillance is based on traditional
protocols and classical microbiology. Innovation in monitoring is required not
only to enhance safety or speed up controls but also to prevent cross infections
due to novel or uncultivable pathogens. In order to improve surveillance
monitoring, we propose that biological fluid microflora (mf) on reprocessed
devices is a potential indicator of sanitation failure, when tested by an mfDNA
based approach. The survey focused on oral microflora traces in dental care
settings. METHODS: Experimental tests (n = 48) and an "in field" trial (n = 83)
were performed on dental instruments. Conventional microbiology and amplification
of bacterial genes by multiple real-time PCR were applied to detect traces of
salivary microflora. Six different sanitation protocols were considered. A
monitoring protocol was developed and performance of the mfDNA assay was
evaluated by sensitivity and specificity. RESULTS: Contaminated samples resulted
positive for saliva traces by the proposed approach (CT < 35). In accordance with
guidelines, only fully sanitized samples were considered negative (100 %).
Culture-based tests confirmed disinfectant efficacy, but failed in detecting
incomplete sanitation. The method provided sensitivity and specificity over 95 %.
CONCLUSIONS: The principle of detecting biological fluids by mfDNA analysis seems
promising for monitoring the effectiveness of instrument reprocessing. The
molecular approach is simple, fast and can provide a valid support for
surveillance in dental care or other hospital settings.
PMID- 27507587
TI - Quorum-sensing in yeast and its potential in wine making.
AB - This mini-review synthesises the present knowledge of microbial quorum-sensing,
with a specific focus on quorum-sensing in yeast, and especially in wine yeast.
In vine and wine ecosystems, yeast co-interact with a large variety of
microorganisms, thereby affecting the fermentation process and, consequently, the
flavour of the wine. The precise connections between microbial interactions and
quorum-sensing remain unclear, but we describe here how and when some species
start to produce quorum-sensing molecules to synchronously adapt their collective
behaviour to new conditions. In Saccharomyces cerevisiae, the quorum-sensing
molecules were identified as 2-phenylethanol and tryptophol. However, it was
recently shown that also a quorum-sensing molecule formerly identified only in
Candida albicans, tyrosol, appears to be regulated in S. cerevisiae according to
cell density. This review describes the methods for detection and quantification
of those quorum-sensing molecules, their underlying mechanisms of action, and
their genetic background. It also examines the external stimuli that evoke the
quorum-sensing mechanism in the wine-processing environment. The review closes
with insight into the biotechnological applications that are already making use
of the advantages of quorum-sensing systems and indicates the important questions
that still need to be addressed in future research into quorum-sensing.
PMID- 27507588
TI - Integrated analyses using RNA-Seq data reveal viral genomes, single nucleotide
variations, the phylogenetic relationship, and recombination for Apple stem
grooving virus.
AB - BACKGROUND: Next-generation sequencing (NGS) provides many possibilities for
plant virology research. In this study, we performed integrated analyses using
plant transcriptome data for plant virus identification using Apple stem grooving
virus (ASGV) as an exemplar virus. We used 15 publicly available transcriptome
libraries from three different studies, two mRNA-Seq studies and a small RNA-Seq
study. RESULTS: We de novo assembled nearly complete genomes of ASGV isolates
Fuji and Cuiguan from apple and pear transcriptomes, respectively, and identified
single nucleotide variations (SNVs) of ASGV within the transcriptomes. We
demonstrated the application of NGS raw data to confirm viral infections in the
plant transcriptomes. In addition, we compared the usability of two de novo
assemblers, Trinity and Velvet, for virus identification and genome assembly. A
phylogenetic tree revealed that ASGV and Citrus tatter leaf virus (CTLV) are the
same virus, which was divided into two clades. Recombination analyses identified
six recombination events from 21 viral genomes. CONCLUSIONS: Taken together, our
in silico analyses using NGS data provide a successful application of plant
transcriptomes to reveal extensive information associated with viral genome
assembly, SNVs, phylogenetic relationships, and genetic recombination.
PMID- 27507589
TI - Curcumin improves atorvastatin-induced myotoxicity in rats: Histopathological and
biochemical evidence.
AB - Atorvastatin is considered to be one of the most commonly used of all statins
anti-hyperlipidemic drugs despite the fact that there is much controversy about
its safety. Its therapeutic use becomes severely limited by the hazards of
inducing myotoxicity. Curcumin is one of the safe spices that have
chemoprotection and cytoprotection effects against endogenous and exogenous
noxious stimuli. This study investigates the effect of curcumin on atorvastatin
sub-chronic use-induced myotoxicity in rats by the assessment of serum creatinine
phosphokinase, lactic acid dehydrogenase, myoglobin, troponin, potassium,
creatinine, and histopathological changes of skeletal, smooth, and cardiac
muscles by light and electron microscope examination. Eighty adult albino rats
were divided into four groups; each group consists of 20 rats. The control group
received water, the second group received atorvastatin, the third group received
curcumin, and the fourth group received curcumin with atorvastatin for 90 days by
gastric gavage. The prolonged use of atorvastatin induced significant
abnormalities of all myotoxicity biomarkers associated with histopathological and
ultrastructural changes in the different types of the muscles. Co-administration
of curcumin with sub-chronic use of atorvastatin led to an improvement in
myotoxicity manifestations.
PMID- 27507590
TI - Subjective and clinical assessment criteria suggestive for five clinical patterns
discernible in nonspecific neck pain patients. A Delphi-survey of clinical
experts.
AB - BACKGROUND: Nonspecific neck pain patients form a heterogeneous group with
different musculoskeletal impairments. Classifying nonspecific neck pain patients
into subgroups based on clinical characteristics might lead to more comprehensive
diagnoses and can guide effective management. OBJECTIVE: To establish consensus
among a group of experts regarding the clinical criteria suggestive of a clinical
dominance of 'articular', 'myofascial', 'neural', 'central' and 'sensorimotor
control' dysfunction patterns distinguishable in patients with nonspecific neck
pain. STUDY DESIGN: Delphi study. METHODS: A focus group with 10 academic experts
was organized to elaborate on the different dysfunction patterns discernible in
neck pain patients. Consecutively, a 3-round online Delphi-survey was designed to
obtain consensual symptoms and physical examination findings for the 5 distinct
dysfunction patterns resulting from the focus group. RESULTS: A total of 21
musculoskeletal physical therapists from Belgium and the Netherlands experienced
in assessing and treating neck pain patients completed the 3-round Delphi-survey.
Respectively, 33 (response rate, 100.0%), 27 (81.8%) and 21 (63.6%) respondents
replied to rounds 1, 2 and 3. Eighteen 'articular', 16 'myofascial', 20 'neural',
18 'central' and 10 'sensorimotor control' clinical indicators reached a
predefined >=80% consensus level. CONCLUSION: These indicators suggestive of a
clinical dominance of 'articular', 'myofascial', 'neural', 'central', and
'sensorimotor control' dysfunction patterns may help clinicians to assess and
diagnose patients with nonspecific neck pain. Future validity testing is needed
to determine how these criteria may help to improve the outcome of physical
therapy interventions in nonspecific neck pain patients.
PMID- 27507592
TI - Topological spin and valley pumping in silicene.
AB - We propose to realize adiabatic topological spin and valley pumping by using
silicene, subject to the modulation of an in-plane ac electric field with
amplitude Ey and a vertical electric field consisting of an electrostatic
component and an ac component with amplitudes and . By tuning and , topological
valley pumping or spin-valley pumping can be achieved. The low-noise valley and
spin currents generated can be useful in valleytronic and spintronic
applications. Our work also demonstrates that bulk topological spin or valley
pumping is a general characteristic effect of two-dimensional topological
insulators, irrelevant to the edge state physics.
PMID- 27507591
TI - Environmental NO2 and CO Exposure: Ignored Factors Associated with Uremic
Pruritus in Patients Undergoing Hemodialysis.
AB - Uremic pruritus (UP), also known as chronic kidney disease-associated pruritus,
is a common and disabling symptom in patients undergoing maintenance hemodialysis
(MHD). The pathogenesis of UP is multifactorial and poorly understood. Outdoor
air pollution has well-known effects on the health of patients with allergic
diseases through an inflammatory process. Air pollution-induced inflammation
could occur in the skin and aggravate skin symptoms such as pruritus or impair
epidermal barrier function. To assess the role of air pollutants, and other
clinical variables on uremic pruritus (UP) in HD patients, we recruited 866
patients on maintenance HD. We analyzed the following variables for association
with UP: average previous 12-month and 24-month background concentrations for
nitrogen dioxide (NO2) and carbon monoxide (CO), and suspended particulate matter
of <2.5 MUm (PM2.5). In a multivariate logistic regression, hemodialysis
duration, serum ferritin levels, low-density lipoprotein levels, and
environmental NO2/CO levels were positively associated with UP, and serum albumin
levels were negatively associated with UP. This cross-sectional study showed that
air pollutants such as NO2 and CO might be associated with UP in patients with
MHD.
PMID- 27507593
TI - Nutraceuticals in Neurodegeneration and Aging.
PMID- 27507594
TI - Phytochemicals in animal health: diet selection and trade-offs between costs and
benefits.
AB - Many plant tissues contain plant secondary compounds (PSC), which have long been
recognised as defensive chemicals that deter herbivory via their toxic effects.
However, herbivores may also benefit from including PSC into their diets. Plant
derived phenolics, terpenes and alkaloids have antiparasitic properties and
sesquiterpene lactones have antibacterial, antifungal and antiparasitic
properties. These actions are in part a consequence of the negative actions that
PSC exert across several trophic levels, including the bacteria, parasites and
fungi that inhabit herbivores' bodies. Given the dual action, toxin and medicine,
it is possible to hypothesise that self-selection of PSC by herbivores should
occur when the benefits outweigh the costs of PSC ingestion. Recent research
suggests that sheep and goats self-medicate against parasitic infections. They
increase preference for condensed tannin-containing foods when experiencing a
parasitic burden. This behaviour improves health; it is triggered by parasitism
and weakens when parasitism subsides. However, the causes underlying these
responses are not straightforward when viewed under a unidimensional cost-benefit
analysis. This is because the intensity of antinutritional/toxic and medicinal
effects of PSC is not static or just dependent upon the isolated post-ingestive
effects of single PSC. Nutrient-PSC and PSC-PSC interactions, social models, as
well as feeding patterns, all influence the perceived net benefit of
incorporating medicines into a diet. A better understanding of the net benefit of
self-medication in complex feeding environments will allow for the development of
innovative managing strategies aimed at providing the food alternatives and
conditions for improving the nutrition, health and welfare of grazing animals.
PMID- 27507596
TI - Competing amination and C-H arylation pathways in Pd/xantphos-catalyzed
transformations of binaphthyl triflates: switchable routes to chiral amines and
helicene derivatives.
AB - A Pd(OAc)2/xantphos catalyst system was found effective for benzylaminations of
binaphthyl 2-triflates bearing a variety of alkyl, benzyl, and substituted phenyl
substituents at the 2'-position. With 2'-aryl substituents, an intramolecular Pd
catalyzed C-H arylation was observed as a competing side reaction under some
conditions. By adjusting the solvent and quantity of the amine, the reaction was
optimized to favor either the amination or the C-H arylation pathway, affording
two distinct and potentially useful sets of products. The amines represent
tunable chiral ligand precursors, while the C-H arylation pathway affords a
series of benzofused [5]helicene derivatives. Kinetic studies and activation
parameters for the C-H arylation pathway, supported by DFT calculations, are
consistent with a concerted metalation-deprotonation (CMD) mechanism involving a
Pd-bound carbonate as the base. Xantphos is proposed to facilitate the turnover
limiting inner-sphere CMD step by acting as a hemilabile ligand, while its wide
bite angle engenders a low reductive elimination barrier.
PMID- 27507595
TI - The interaction of fasting, caloric restriction, and diet-induced obesity with
17beta-estradiol on the expression of KNDy neuropeptides and their receptors in
the female mouse.
AB - Arcuate neurons that coexpress kisspeptin (Kiss1), neurokinin B (Tac2), and
dynorphin (Pdyn) mediate negative feedback of 17beta-estradiol (E2) on the HPG
axis. Previous studies report that fasting and caloric restriction reduce arcuate
Kiss1 expression. The objective of this study was to determine the interactions
of E2 with fasting, caloric restriction, and diet-induced obesity on KNDy gene
and receptor expression. Ovariectomized female mice were separated into control
and estradiol benzoate (E2B)-treated groups. E2B decreased Kiss1 and the
tachykinin 2 receptor, Tac3r, in ARC tissue and Tac2 in Tac2 neurons. Diet
induced obesity decreased Kiss1 in oil-treated animals and the kisspeptin
receptor, Kiss1r and Tac3r in the ARC of E2B-treated animals. Chronic caloric
(30%) restriction reduced all three neuropeptides in oil-treated females and
Kiss1r by E2B in CR animals. Taken together, our experiments suggest that
steroidal environment and energy state negatively regulate KNDy gene expression
in both ARC and Tac2 neurons.
PMID- 27507597
TI - Label-free optical detection of age-related and diabetic oxidative damage in
human aqueous humors.
AB - In this study, we investigate the biochemical characteristics of oxidative stress
in age-related macular degeneration (AMD) and diabetic retinopathy (DR) by
analyzing aqueous humors. Nondiabetic cataract aqueous humor was used as the
control. The level of oxidative damage was evaluated based on changes in Raman
spectral intensity. Seven prominent peaks were detected at 1002, 1043, 1062,
1352, 1419, 1454, and 1656 cm-1 . We proposed four multimodal biomarkers to
distinguish these peaks based on the ratios of Raman intensities in two
wavelengths, including CHO (C-O stretching or C-O-H bending modes), AG (adenine
and guanine), PRO-AG (protein and AG), and PHEalpha (phenylalanine symmetric ring
breath and amide I alpha-helix) markers. The presence of oxidative damage was
detected by CHO and AG markers associated with C-O stretching, C-O-H bending
modes in carbohydrates (1043 cm-1 ), and the nucleic acids adenine and guanine
(1352 cm-1 ), respectively. DR-related oxidative damage was identified by PRO-AG
and PHEalpha markers associated with adenine, guanine, and protein components
(1419 and 1454 cm-1 ) and amide I alpha-helix protein structure (1656 cm-1 ),
respectively. AMD-related oxidative damage was identified by four biomarkers.
Four multimodal biomarkers with simple linear threshold values achieved high
sensitivity of 100% and high specificity of 100% for classifying oxidative stress
induced AMD and DR diseases. Therefore, Raman-based label-free optical detection
is effective for detecting the presence of age-related or diabetic oxidative
damage in aqueous humor.
PMID- 27507598
TI - Neuroprotective effects of antibodies on retinal ganglion cells in an adolescent
retina organ culture.
AB - Glaucoma, a neurodegenerative disease, is characterized by a progressive loss of
retinal ganglion cells (rgc). Up- and down-regulated autoantibody
immunoreactivities in glaucoma patients have been demonstrated. Previous studies
showed protective effects of down-regulated antibodies [gamma (gamma)-synuclein
and glial fibrillary acidic protein [GFAP]) on neuroretinal cells. The aim of
this study was to test these protective antibody effects on rgc in an organ
culture model and to get a better understanding of cell-cell interactions of the
retina in the context of the protective effect. We used an adolescent retinal
organ culture (pig) with an incubation time of up to 4 days. Retinal explants
were incubated with different antibodies for 24 h (anti-GFAP, anti-gamma
synuclein and anti-myoglobin antibody as a control). Brn3a and TUNEL staining
were performed. We also conducted glutamine synthetase staining and
quantification of the retinal explants. Mass spectrometry analyses were performed
as well as protein analyses via microarray. We detected a continuous decrease of
rgc/mm in the retinal explants throughout the 4 days of incubation with increased
TUNEL rgc staining. Immunohistochemical analyses showed a protective effect of
anti-gamma-synuclein (increased rgc/mm of 41%) and anti-GFAP antibodies
(increased rgc/mm of 37%). Mass spectrometric, microarray and immunohistochemical
analyses demonstrated Muller cell involvement and decreased endoplasmic reticulum
stress response in the antibody-treated retinae. We could detect that the tested
antibodies have a protective effect on rgc which seems to be the result of
reduced stress levels in the retina as well as a shift of glutamine synthetase
localization in the endfeet of the Muller cells towards the inner retinal layer.
Loss of retinal ganglion cells (rgc) in glaucoma leads to blindness. Several
antibodies are down-regulated in glaucoma patients. Our aim was to test if these
antibodies have a protective effect of rgc in a retinal organ culture. This could
be shown with an increase of rgc numbers. This effect results through reduced
stress levels and the shift of glutamine synthetase localization.
PMID- 27507599
TI - Remodeling of injectable, low-viscosity polymer/ceramic bone grafts in a sheep
femoral defect model.
AB - Ceramic/polymer composite bone grafts offer the potential advantage of combining
the osteoconductivity of ceramic component with the ductility of polymeric
component, resulting in a graft that meets many of the desired properties for
bone void fillers (BVF). However, the relative contributions of the polymer and
ceramic components to bone healing are not well understood. In this study, we
compared remodeling of low-viscosity (LV) ceramic/poly(ester urethane) composites
to a ceramic BVF control in a sheep femoral condyle plug defect model. LV
composites incorporating either ceramic (LV/CM) or allograft bone (LV/A)
particles were evaluated. We hypothesized that LV/CM composites which have the
advantageous handling properties of injectability, flowability, and settability
would heal comparably to the CM control, which was evaluated for up to 2 years to
study its long-term degradation properties. Remodeling of LV/CM was comparable to
that observed for the CM control, as evidenced by new bone formation on the
surface of the ceramic particles. At early time points (4 months), LV/CM
composites healed similar to the ceramic clinical control, while LV/A components
showed more variable healing due to osteoclast-mediated resorption of the
allograft particles. At longer time points (12-15 months), healing of LV/CM
composites was more variable due to the nonhomogeneous distribution and lower
concentration of the ceramic particles compared to the ceramic clinical control.
Resorption of the ceramic particles was almost complete at 2 years. This study
highlights the importance of optimizing the loading and distribution of ceramic
particles in polymer/ceramic composites to maximize bone healing. (c) 2016 Wiley
Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2333-2343,
2017.
PMID- 27507600
TI - Expectations and perspectives of ovarian cancer patients about cancer management
in Romania. The international NOGGO-ENGOT trial: EXPRESSION III.
AB - We have investigated a relational model of expectations and preferences among
ovarian cancer patients centred on physician-patient communication, treatment
approach, and the need for information. Consecutive patients anonymously filled
in the EXPRESSION III questionnaire between 2009 and 2012. Following descriptive
statistics, structural equation modelling was used to analyse the relationships
between physician's evaluation by the patient (PEP), result of therapy (RT), need
for changes in treatment (NCT) and patient's desire to be informed (PD). From a
total of 108 patients, 53 (49.1%) knew their disease stage, 103 (95.4%) underwent
surgery, 91 (84.3%) had chemotherapy and 51 (46.3%) relapsed. The final model
demonstrated a good fit of data with fit indices >0.90. There was a significant
positive effect of PEP on RT and a significant negative effect of PEP on NCT,
with the final model explaining 84% of the NCT variance. Physicians represent the
main point of contact, not only as a source of information about the disease and
various treatment options, but also in the coping processes. As patients benefit
from completeness of medical consultations, their awareness of the treatment
outcome increases, while a negative perception of the physician leads to a desire
to make changes in therapy.
PMID- 27507601
TI - Acetylcholine-hydrolyzing activities in soluble brain fraction: Characterization
with reversible and irreversible inhibitors.
AB - Some effects of organophosphorus compounds (OPs) esters cannot be explained
through actions on currently recognized targets acetylcholinesterase or
neuropathy target esterase (NTE). In soluble chicken brain fraction, three
components (Ealpha, Ebeta and Egamma) of pheny lvalerate esterase activity
(PVase) were kinetically discriminated and their relationship with acetylcholine
hydrolyzing activity (cholinesterase activity) were studied in previous works. In
this work, four enzymatic components (CS1, CS2, CS3 and CS4) of cholinesterase
activity have been discriminated in soluble fraction, according to their
sensitivity to irreversible inhibitors mipafox, paraoxon, PMSF and iso-OMPA and
to reversible inhibitors ethopropazine and BW284C51. Cholinesterase component CS1
can be related to the Ealpha component of PVase activity and identified as
butyrylcholinesterase (BuChE). No association and similarities can be stablished
among the other PVase component (Ebeta and Egamma) with the other cholinesterase
components (CS2, CS3, CS4). The kinetic analysis has allowed us to stablish a
method for discriminating the enzymatic component based on a simple test with two
inhibitors. It can be used as biomarker in toxicological studies and for
monitoring these cholinesterase components during isolation and molecular
identification processes, which will allow OP toxicity to be understood by a
multi-target approach.
PMID- 27507602
TI - N-phenylmaleimides affect adipogenesis and present antitumor activity through
reduction of FASN expression.
AB - In light of the evidence that in contrast to most healthy tissues, several
neoplasms overexpress fatty acid synthase (FASN) upon their dependence on
increased lipogenesis; targeting of this protein is being considered as a
valuable strategy in anticancer drug development. This can be particularly
relevant for aggressive tumors such as melanoma in which FASN overexpression has
been associated with increased depth of invasion and worse prognosis. We have
previously shown that a sub-class of cyclic imides, the N-phenylmaleimides,
presented antitumor activity against L1210 leukemia and B16F10 melanoma with
evidences of interference in the energetic metabolism. Here, we aimed to
investigate if some selected N-phenylmaleimides (M1 and M5) interfere with fatty
acids metabolism and its relation with cancer. For that, a model of pre
adipocytes differentiation (3T3-L1 cells) and also human melanoma cells (SK-Mel
147) were used. As results, when 3T3-L1 cells were exposed to non-cytotoxic
concentrations of M1 and M5 in the presence of an adipogenic cocktail,
intracellular lipid content decreased by 26-36%, marking the inhibition of
adipocyte differentiation. High selectivity indexes were obtained for both
compounds for tumoral cells. Cell cycle phases analysis revealed a remarkable
proportion of cells with DNA fragmentation after their exposure to M1 and M5.
This was correlated to both apoptosis and necrosis, showed by Annexin-V/PI assay.
Furthermore, M1 and M5 reduced FASN expression by 19-39%, respectively. In
conclusion, M1 and M5 presented antiadipogenic and antitumoral activities. The
antitumoral activity that was associated to apoptosis and necrosis is a possible
consequence of the FASN reduction, which in turn, might result in a fuel decrease
to cell proliferation. As it happens with antiangiogenic activity, reduction of
fatty acid synthesis might be a potential target for cancer treatment in a
strategy of hunger-strike, which valorizes these N-phenylmaleimides as candidates
for drug development.
PMID- 27507603
TI - Controllable in-situ cell electroporation with cell positioning and impedance
monitoring using micro electrode array.
AB - This paper reports a novel microarray chip for in-situ, real-time and selective
electroporation on individual cells integrated with cell positioning and
impedance monitoring. An array of quadrupole-electrode units (termed positioning
electrodes) and pairs of planar center electrodes located at the centers of each
quadrupole-electrode unit were fabricated on the chip. The positioning electrodes
are used to trap and position living cells onto the center electrodes based on
negative dielectrophoresis (nDEP). The center electrodes are used for in-situ
cell electroporation, and also used to measure cell impedance for monitoring
cellular dynamics in real time. Controllably selective electroporation and
electrical measurement on the cells in array are realized. We present an evidence
of selective electroporation through use of fluorescent dyes. Subsequently we use
in-situ and real-time impedance measurement to monitor the process, which
demonstrates the dynamic behavior of the cell electroporation. Finally, we show
the use of this device to perform successful transfection onto individual HeLa
cells with vector DNA encoding a green fluorescent.
PMID- 27507604
TI - Salicylic acid confers salt tolerance in potato plants by improving water
relations, gaseous exchange, antioxidant activities and osmoregulation.
AB - BACKGROUND: Potato is an important vegetable; however, salt stress drastically
affects its growth and yield. A pot experiment was therefore conducted to assess
salicylic acid efficacy in improving performance of potato cultivars, grown under
salt stress (50 mmol L-1 ). Salicylic acid at 0.5 mmol L-1 was sprayed on to
potato plants after 1 week of salinity application. RESULTS: Salt stress effects
were ameliorated by salicylic acid effectively in both the studied cultivars. N-Y
LARA proved more responsive to salicylic acid application than 720-110 NARC,
which confirmed genetic variation between cultivars. Salicylic acid scavenged
reactive oxygen species by improving antioxidant enzyme activities (superoxide
dismutase, catalase, peroxidases) and regulating osmotic adjustment (proline,
phenolic contents), which led to enhanced water relation and gaseous exchange
attributes, and thereby increased potassium availability and reduced sodium
content in potato leaves. Moreover, potato tuber yield showed a positive
correlation with potassium content, photosynthesis and antioxidant enzyme
activities. CONCLUSION: Salt tolerance efficacy of salicylic acid is
authenticated in improving potato crop performance under salt stress. Salicylic
acid effect was more pronounced in N-Y LARA, reflecting greater tolerance than
720-110 NARC, which was confirmed as a susceptible cultivar. Hence salicylic acid
at 0.5 mmol L-1 and cultivation of N-Y LARA may be recommended in saline soil.
(c) 2016 Society of Chemical Industry.
PMID- 27507606
TI - The Correlation of Increased CRP Levels with NFKB1 and TLR2 Polymorphisms in the
Case of Morbid Obesity.
AB - Morbid obesity (MO) is associated with an increase in circulating levels of
systemic acute phase proteins such as C-reactive protein (CRP). Toll-like
receptor is possible candidate for inflammatory responses which is mainly
mediated by NFKB1. The aim of this study was to investigate the relationship
between NFKB1 and Toll-like receptor (TLR) 2 polymorphisms and the risk of MO in
a Turkish population in the context of CRP serum levels which may contribute to
susceptibility to the disease. We analysed the distribution of NFKB1-94 ins/del
ATTG rs28362491 and TLR2 Arg753Gln rs5743708 polymorphisms using PCR-RFLP method
and CRP serum levels using ELISA method in 213 MO and 200 healthy controls. The
frequency of the ins/ins genotype and ins allele of rs28362491 was significantly
higher in the patients compared to control group (P: 0.0309; P: 0.0421,
respectively). Additionally, the frequency of GG genotype and G allele of
rs5743708 was found to be statistically higher in the patient group (P: 0.0421; P
< 0.0001, respectively). In addition, serum CRP levels (>20 mg/l) in MO patients
with ins/ins genotype were significantly higher than in patients with del/ins
genotype (P: 0.0309). Serum CRP levels were also higher in MO patients with GG
genotype and G allele (P: 0.0001). According to combined analysis, the wild type
of rs28362491 and rs5743708 polymorphisms (ins/ins/GG genotype) was also
significantly higher in the patient group versus the control group when compared
with the combined ins/ins/GA and del/ins/GA genotype (P < 0.0001). Therefore, our
findings suggest that rs28362491 and rs5743708 polymorphisms were significantly
associated with MO disease through acting by modulating serum CRP levels.
PMID- 27507607
TI - How Are Short Exons Flanked by Long Introns Defined and Committed to Splicing?
AB - The splice sites (SSs) delimiting an intron are brought together in the earliest
step of spliceosome assembly yet it remains obscure how SS pairing occurs,
especially when introns are thousands of nucleotides long. Splicing occurs in
vivo in mammals within minutes regardless of intron length, implying that SS
pairing can instantly follow transcription. Also, factors required for SS
pairing, such as the U1 small nuclear ribonucleoprotein (snRNP) and U2AF65,
associate with RNA polymerase II (RNAPII), while nucleosomes preferentially bind
exonic sequences and associate with U2 snRNP. Based on recent publications, we
assume that the 5' SS-bound U1 snRNP can remain tethered to RNAPII until complete
synthesis of the downstream intron and exon. An additional U1 snRNP then binds
the downstream 5' SS, whereas the RNAPII-associated U2AF65 binds the upstream 3'
SS to facilitate SS pairing along with exon definition. Next, the nucleosome
associated U2 snRNP binds the branch site to advance splicing complex assembly.
This may explain how RNAPII and chromatin are involved in spliceosome assembly
and how introns lengthened during evolution with a relatively minimal compromise
in splicing.
PMID- 27507609
TI - Recognizing Plant Defense Priming.
AB - Defense priming conditions diverse plant species for the superinduction of
defense, often resulting in enhanced pest and disease resistance and abiotic
stress tolerance. Here, we propose a guideline that might assist the plant
research community in a consistent assessment of defense priming in plants.
PMID- 27507610
TI - Bone mineral density in anorexia nervosa: Only weight and menses recovery?
AB - INTRODUCTION: The study objectives were to analyze the presence of reduced bone
mass in a sample of patients with anorexia nervosa (AN) and amenorrhea, to assess
Bone Mineral Density (BMD) recovery after having a normal weight is reached and
regular menses are resumed, and to predict BMD after a treatment period
considering different variables (baseline BMD, baseline and final body mass index
(BMI), treatment duration). MATERIAL & METHODS: 35 patients with AN (mean age
20.57+/-5.77) were studied at treatment start (T0) and after they had recovered
their normal weight and regular menses (T1) in order to measure their BMD using
quantitative computed tomography (QCT) of the lumbar spine (L2-L4). RESULTS: At
T0, 2.86% of patients had normal BMD, while a reduced bone mass consistent with
osteopenia or with osteoporosis was found in 22.86% and 74.28% of patients
respectively. At T1, the percentages were 20%, 20%, and 60% respectively. No
significant differences were seen in L2-L3 and mean BMD (L2-L4). A significant
difference was however found for L4 (p<0.05). A positive relationship was seen
between final body mass index (BMI) and final BMD in patients with T0-T1>11
months, but not when the time period was <=11 months. CONCLUSIONS: This follow-up
study of changes not only in BMD but also in BMI and recovery of menses has
clinical relevance from the viewpoint of the day-by-day treatment process. Use of
QCT makes the study more relevant because this is a more advanced technique that
allows for differentiating trabecular and cortical bone.
PMID- 27507608
TI - Cockayne syndrome: Clinical features, model systems and pathways.
AB - Cockayne syndrome (CS) is a disorder characterized by a variety of clinical
features including cachectic dwarfism, severe neurological manifestations
including microcephaly and cognitive deficits, pigmentary retinopathy, cataracts,
sensorineural deafness, and ambulatory and feeding difficulties, leading to death
by 12 years of age on average. It is an autosomal recessive disorder, with a
prevalence of approximately 2.5 per million. There are several phenotypes (1-3)
and two complementation groups (CSA and CSB), and CS overlaps with xeroderma
pigmentosum (XP). It has been considered a progeria, and many of the clinical
features resemble accelerated aging. As such, the study of CS affords an
opportunity to better understand the underlying mechanisms of aging. The
molecular basis of CS has traditionally been ascribed to defects in transcription
and transcription-coupled nucleotide excision repair (TC-NER). However, recent
work suggests that defects in base excision DNA repair and mitochondrial
functions may also play key roles. This opens up the possibility for molecular
interventions in CS, and by extrapolation, possibly in aging.
PMID- 27507611
TI - Effects of dietary supplementation with EPA and/or alpha-lipoic acid on adipose
tissue transcriptomic profile of healthy overweight/obese women following a
hypocaloric diet.
AB - In obesity, the increment of adiposity levels disrupts the whole body
homeostasis, promoting an over production of oxidants and inflammatory mediators.
The current study aimed to characterize the transcriptomic changes promoted by
supplementation with eicosapentaenoic acid (EPA, 1.3 g/day), alpha-lipoic acid
(0.3 g/day), or both (EPA + alpha-lipoic acid, 1.3 g/day + 0.3 g/day) in
subcutaneous abdominal adipose tissue from overweight/obese healthy women, who
followed a hypocaloric diet (30% of total energy expenditure) during ten weeks,
by using a microarray approach. At the end of the intervention, a total of 33,297
genes were analyzed using Affymetrix GeneChip arrays. EPA promoted changes in
extracellular matrix remodeling gene expression, besides a rise of genes
associated with either chemotaxis or wound repair. alpha-Lipoic acid decreased
expression of genes related with cell adhesion and inflammation. Furthermore,
alpha-lipoic acid, especially in combination with EPA, upregulated the expression
of genes associated with lipid catabolism while downregulated genes involved in
lipids storage. Together, all these data suggest that some of the metabolic
effects of EPA and alpha-lipoic acid could be related to their regulatory actions
on adipose tissue metabolism. (c) 2016 BioFactors, 43(1):117-131, 2017.
PMID- 27507612
TI - "Non-Toxic" Proteins of the Botulinum Toxin Complex Exert In-vivo Toxicity.
AB - The botulinum neurotoxin (BoNT) causes muscle paralysis and is the most potent
toxin in nature. BoNT is associated with a complex of auxiliary "Non-Toxic"
proteins, which constitute a large-sized toxin complex (L-TC). However, here we
report that the "Non-Toxic" complex of serotype D botulinum L-TC, when
administered to rats, exerts in-vivo toxicity on small-intestinal villi.
Moreover, Serotype C and D of the "Non-Toxic" complex, but not BoNT, induced
vacuole-formation in a rat intestinal epithelial cell line (IEC-6), resulting in
cell death. Our results suggest that the vacuole was formed in a manner distinct
from the mechanism by which Helicobacter pylori vacuolating toxin (VacA) and
Vibrio cholerae haemolysin induce vacuolation. We therefore hypothesise that the
serotype C and D botulinum toxin complex is a functional hybrid of the neurotoxin
and vacuolating toxin (VT) which arose from horizontal gene transfer from an
ancestral BoNT-producing bacterium to a hypothetical VT-producing bacterium.
PMID- 27507613
TI - The secondary frame in spider orb webs: the detail that makes the difference.
AB - Spider orb webs are multifunctional structures, the main function of which is to
dissipate the kinetic energy of the impacting prey, while minimizing structural
damage. There is no single explanation for their remarkable strength and
ductility. However, it is clear that topology is decisive in the structural
performance upon impact, and the arrangement of the different silk threads in the
web must also exert an effect. The aim of this study is to show how a slight
variation in the geometry markedly affects the prey-capture ability of spider orb
webs. The study is focused on the secondary frame, a thread interposed between
radial and primary frame strands, the importance of which has not been examined
until now. The simulation of the impact performance of webs using different
lengths of the secondary frame clarifies its structural role, which has proven to
be decisive. Furthermore, the study explains why secondary frame threads of
moderate length, as commonly encountered, enable the capture of prey with higher
energy without a marked increase in the volume of silk used.
PMID- 27507614
TI - NKD1 correlates with a poor prognosis and inhibits cell proliferation by inducing
p53 expression in hepatocellular carcinoma.
AB - Naked cuticle 1 (NKD1), a negative regulator of the Wnt signaling pathway, is
abnormally expressed in many types of malignant tumors. Yet the role and
mechanism of NKD1 in hepatocellular carcinoma (HCC) cell proliferation and its
relationship with HCC patients' prognosis have been poorly characterized. In the
present study, real-time polymerase chain reaction (PCR) was used to examine the
mRNA expression patterns of NKD1 in the tissues of 60 patients with HCC and
corresponding adjacent non-tumor tissues and found that NKD1 mRNA expression in
HCC tissues was relatively lower than that in non-tumor tissues and negatively
correlated with tumor size. Kaplan-Meier survival curves uncovered that patients
with lower NKD1 expression had a poorer post-operative prognosis than those with
higher expression. In addition, over-expression of NKD1 inhibited the HCC cell
proliferation ability, whereas knockdown of NKD1 had the opposite effect. In vivo
assays showed that mice injected with SMMC-7721 + control cells had bigger tumor
nodules than those injected with SMMC-7721 + NKD1. Mechanism studies demonstrated
that NKD1 repressed HCC cell proliferation by inducing p53 expression. Taken
together, our study revealed that NKD1 mRNA expression was downregulated in HCC
tissues and correlated with a poor prognosis. NKD1 inhibited HCC cell
proliferation by inducing p53 expression.
PMID- 27507616
TI - Integrated Epigenomics Analysis Reveals a DNA Methylation Panel for Endometrial
Cancer Detection Using Cervical Scrapings.
AB - PURPOSE: Endometrial cancer is a common gynecologic cancer whose incidence is
increasing annually worldwide. Current methods to detect endometrial cancer are
unreliable and biomarkers are unsatisfactory for screening. Cervical scrapings
were reported as a potential source of material for molecular testing. DNA
methylation is a promising cancer biomarker, but limited use for detecting
endometrial cancer. EXPERIMENTAL DESIGN: We analyzed two methylomics databases of
endometrioid-type endometrial cancer. Using nonnegative matrix factorization
algorithm clustered the methylation pattern and reduced the candidate genes. We
verified in pools DNA from endometrial cancer tissues and cervical scrapings, and
validated in 146 cervical scrapings from patients with endometrioid-type
endometrial cancer (n = 50), uterine myoma (n = 40), and healthy controls (n =
56) using quantitative methylation-specific PCR (QMSP). The logistic regression
was used to evaluate the performance of methylation signal and gene combination.
RESULTS: We filtered out 180 methylated genes, which constituted four consensus
clusters. Serial testing of tissues and cervical scrapings detected 14 genes that
are hypermethylated in endometrial cancer. Three genes, BHLHE22, CDO1, and CELF4,
had the best performance. Individual genes were sensitivity of 83.7%-96.0% and
specificity of 78.7%-96.0%. A panel comprising any two of the three
hypermethylated genes reached a sensitivity of 91.8%, specificity of 95.5%, and
odds ratio of 236.3 (95% confidence interval, 56.4-989.6). These markers were
also applied to cervical scrapings of type II endometrial cancer patients, and
detected in 13 of 14 patients. CONCLUSIONS: This study demonstrates the potential
use of methylated BHLHE22/CDO1/CELF4 panel for endometrial cancer screening of
cervical scrapings. Clin Cancer Res; 23(1); 263-72. (c)2016 AACR.
PMID- 27507615
TI - Characterization of cancer stem cells from different grades of human colorectal
cancer.
AB - Colorectal cancer (CRC) is one of the most common solid tumors worldwide. Recent
evidence suggests that a population of cancer cells, called cancer stem cells
(CSCs), is responsible for tumor heterogeneity, invasion, metastasis, therapeutic
resistance, and recurrence of CRC. The isolation and characterization of CSCs
using cell surface markers have been reported previously with varying results. In
this study, we investigated a panel of four putative CSC markers, CD44, CD24,
CD166, and EpCAM, to define CRC-CSC. Paraffin embedded tissue samples from
different grades of primary, untreated CRC were analyzed for the expression of
four CSC markers CD44, CD326, CD24, and CD166, using immunohistochemistry. Flow
cytometric analysis of CRC-CSC from HT29 (low grade) and HCT116 (high grade)
human colorectal cancer cell lines was done. Marker-based isolation of CSC and
non-CSC-bulk-tumor cells from HT29 was done using FACS, and tumor sphere assay
was performed. There was a statistically significant difference (p < 0.05) in the
expression of CD44, CD326, and CD166 between cases and controls. A novel cutoff
distribution of CD44 and CD166 was suggested to help for better
immunohistochemical analysis of CRC. Higher prevalence of CSC was seen in high
grade CRC as compared to low-grade CRC. Sorted and cultured CD44 + CD166+ cells
formed tumor spheres, suggesting that these cells, having properties of self
renewal and anchorage independent proliferation, were in fact CSC. Hence, CD44
and CD166 may serve as good CRC-CSC markers when used together with novel cutoff
immunohistochemistry (IHC) expression levels.
PMID- 27507617
TI - Genotype-Guided Dosing Study of FOLFIRI plus Bevacizumab in Patients with
Metastatic Colorectal Cancer.
AB - Purpose:UGT1A1*28 confers a higher risk of toxicity in patients treated with
irinotecan. Patients with *1/*1 and *1/*28 genotypes might tolerate higher than
standard doses of irinotecan. We aimed to identify the MTD of irinotecan in
patients with metastatic colorectal cancer (mCRC) with *1/*1 and *1/*28 genotypes
treated with FOLFIRI plus bevacizumab, and to determine whether bevacizumab
alters irinotecan pharmacokinetics.Experimental Design: Previously untreated
patients with mCRC (25 *1/*1; 23 *1/*28) were given FOLFIRI plus bevacizumab
every 2 weeks. The irinotecan dose was escalated using a 3 + 3 design in each
genotype group as follows: 260, 310, and 370 mg/m2 The MTD was the highest dose
at which <4/10 patients had a dose-limiting toxicity (DLT). Pharmacokinetics of
irinotecan and SN-38 were measured on days 1 to 3 (without bevacizumab) and 15 to
17 (with bevacizumab).Results: For *1/*1 patients, 2 DLTs were observed among 10
patients at 310 mg/m2, while 370 mg/m2 was not tolerated (2 DLTs in 4 patients).
For *1/*28 patients, 2 DLTs were observed among 10 patients at 260 mg/m2, while
310 mg/m2 was not tolerated (4 DLTs in 10 patients). Neutropenia and diarrhea
were the most common DLTs. Changes in the AUCs of irinotecan and SN-38 associated
with bevacizumab treatment were marginal.Conclusions: The MTD of irinotecan in
FOLFIRI plus bevacizumab is 310 mg/m2 for UGT1A1 *1/*1 patients and 260 mg/m2 for
*1/*28 patients. Bevacizumab does not alter the pharmacokinetics of irinotecan.
The antitumor efficacy of these genotype-guided doses should be tested in future
studies of patients with mCRC treated with FOLFIRI plus bevacizumab. Clin Cancer
Res; 23(4); 918-24. (c)2016 AACR.
PMID- 27507618
TI - Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung.
AB - PURPOSE: Although large-cell neuroendocrine carcinoma (LCNEC) of the lung shares
many clinical characteristics with small-cell lung cancer (SCLC), little is known
about its molecular features. We analyzed lung LCNECs to identify biologically
relevant genomic alterations. EXPERIMENTAL DESIGN: We performed targeted capture
sequencing of all the coding exons of 244 cancer-related genes on 78 LCNEC
samples [65 surgically resected cases, including 10 LCNECs combined with non
small cell lung cancer (NSCLC) types analyzed separately, and biopsies of 13
advanced cases]. Frequencies of genetic alterations were compared with those of
141 SCLCs (50 surgically resected cases and biopsies of 91 advanced cases).
RESULTS: We found a relatively high prevalence of inactivating mutations in TP53
(71%) and RB1 (26%), but the mutation frequency in RB1 was lower than that in
SCLCs (40%, P = 0.039). In addition, genetic alterations in the PI3K/AKT/mTOR
pathway were detected in 12 (15%) of the tumors: PIK3CA 3%, PTEN 4%, AKT2 4%,
RICTOR 5%, and mTOR 1%. Other activating alterations were detected in KRAS (6%),
FGFR1 (5%), KIT (4%), ERBB2 (4%), HRAS (1%), and EGFR (1%). Five of 10 cases of
LCNECs combined with NSCLCs harbored previously reported driver gene alterations,
all of which were shared between the two components. The median concordance rate
of candidate somatic mutations between the two components was 71% (range, 60%
100%). CONCLUSIONS: LCNECs have a similar genomic profile to SCLC, including
promising therapeutic targets, such as the PI3K/AKT/mTOR pathway and other gene
alterations. Sequencing-based molecular profiling is warranted in LCNEC for
targeted therapies. Clin Cancer Res; 23(3); 757-65. (c)2016 AACR.
PMID- 27507619
TI - Collaborative study for the validation of an improved HPLC assay for recombinant
IFN-alfa-2.
AB - The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2
include a nonspecific photometric protein assay using albumin as calibrator and a
highly variable cell-based assay for the potency determination of the protective
effects. A request was expressed by the Official Medicines Control Laboratories
(OMCLs) for improved methods for the batch control of recombinant interferon alfa
2 bulk and market surveillance testing of finished products, including those
formulated with Human Serum Albumin (HSA). A HPLC method was developed at the
Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An
initial collaborative study run under the Biological Standardisation Programme
(BSP; study code BSP039) revealed the need for minor changes to improve linearity
of the calibration curves, assay reproducibility and robustness. The goal of the
collaborative study, coded BSP071, was to transfer and further validate this
improved HPLC method. Ten laboratories participated in the study. Four marketed
IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical
Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference
standards from two manufacturers were used for the quantitative assay. The
modified method was successfully transferred to all laboratories despite local
variation in equipment. The resolution between the main and the oxidised forms of
IFN-alfa-2 was improved compared to the results from the BSP039 study. The
improved method even allowed partial resolution of an extra peak after the
principal peak. Symmetry of the main IFN peak was acceptable for all samples in
all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a
and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the
origin and coefficients of determination greater than 0.9995. Assay
repeatability, intermediate precision and reproducibility varied with the tested
sample within acceptable ranges. Test accuracy estimated by comparing the values
obtained by the participants to the declared contents determined by the
manufacturers was good despite the absence of a common reference preparation. In
conclusion, the present study showed that the new method is suitable,
reproducible and transferable. Proposals for the revision of Ph. Eur. texts are
presented.
PMID- 27507620
TI - Dynamics of flexible fibers and vesicles in Poiseuille flow at low Reynolds
number.
AB - The dynamics of flexible fibers and vesicles in unbounded planar Poiseuille flow
at low Reynolds number is shown to exhibit similar basic features, when their
equilibrium (moderate) aspect ratio is the same and vesicle viscosity contrast is
relatively high. Tumbling, lateral migration, accumulation and shape evolution of
these two types of flexible objects are analyzed numerically. The linear
dependence of the accumulation position on relative bending rigidity, and other
universal scalings are derived from the local shear flow approximation.
PMID- 27507621
TI - Assessing the temporal stability of surface functional groups introduced by
plasma treatments on the outer shells of carbon nanotubes.
AB - Plasma treatments are emerging as superior efficiency treatment for high surface
to volume ratio materials to tune functional group densities and alter
crystallinity due to their ability to interact with matter at the nanoscale. The
purpose of this study is to assess for the first time the long term stability of
surface functional groups introduced across the surface of carbon nanotube
materials for a series of oxidative, reductive and neutral plasma treatment
conditions. Both plasma duration dose matrix based exposures and time decay
experiments, whereby the surface energy of the materials was evaluated
periodically over a one-month period, were carried out. Although only few
morphological changes across the graphitic planes of the carbon nanotubes were
found under the uniform plasma treatment conditions, the time dependence of
pertinent work functions, supported by Raman analysis, suggested that the density
of polar groups decreased non-linearly over time prior to reaching saturation
from 7 days post treatment. This work provides critical considerations on the
understanding of the stability of functional groups introduced across high
specific surface area nano-materials used for the design of nano-composites,
adsorptive or separation systems, or sensing materials and where interfacial
interactions are key to the final materials performance.
PMID- 27507622
TI - Effects of confinement on pattern formation in two dimensional systems with
competing interactions.
AB - Template-assisted pattern formation in monolayers of particles with competing
short-range attraction and long-range repulsion interactions (SALR) is studied by
Monte Carlo simulations in a simple generic model [N. G. Almarza et al., J. Chem.
Phys., 2014, 140, 164708]. We focus on densities corresponding to formation of
parallel stripes of particles and on monolayers laterally confined between
straight parallel walls. We analyze both the morphology of the developed
structures and the thermodynamic functions for broad ranges of temperature T and
the separation L2 between the walls. At low temperature stripes parallel to the
boundaries appear, with some corrugation when the distance between the walls does
not match the bulk periodicity of the striped structure. The stripes integrity,
however, is rarely broken for any L2. This structural order is lost at T = TK(L2)
depending on L2 according to a Kelvin-like equation. Above the Kelvin temperature
TK(L2) many topological defects such as breaking or branching of the stripes
appear, but a certain anisotropy in the orientation of the stripes persists.
Finally, at high temperature and away from the walls, the system behaves as an
isotropic fluid of elongated clusters of various lengths and with various numbers
of branches. For L2 optimal for the stripe pattern the heat capacity as a
function of temperature takes the maximum at T = TK(L2).
PMID- 27507624
TI - Ultrafast formation of air-processable and high-quality polymer films on an
aqueous substrate.
AB - Polymer solar cells are attracting attention as next-generation energy sources.
Scalable deposition techniques of high-quality organic films should be guaranteed
to realize highly efficient polymer solar cells in large areas for commercial
viability. Herein, we introduce an ultrafast, scalable, and versatile process for
forming high-quality organic films on an aqueous substrate by utilizing the
spontaneous spreading phenomenon. This approach provides easy control over the
thickness of the films by tuning the spreading conditions, and the films can be
transferred to a variety of secondary substrates. Moreover, the controlled
Marangoni flow and ultrafast removal of solvent during the process cause the
films to have a uniform, high-quality nanomorphology with finely separated phase
domains. Polymer solar cells were fabricated from a mixture of polymer and
fullerene derivatives on an aqueous substrate by using the proposed technique,
and the device exhibited an excellent power conversion efficiency of 8.44 %.
Furthermore, a roll-to-roll production system was proposed as an air-processable
and scalable commercial process for fabricating organic devices.
PMID- 27507623
TI - Sustained treatment of sickle cell mice with haptoglobin increases HO-1 and H
ferritin expression and decreases iron deposition in the kidney without
improvement in kidney function.
AB - There is growing evidence that extracellular haemoglobin and haem mediate
inflammatory and oxidative damage in sickle cell disease. Haptoglobin (Hp), the
scavenger for free haemoglobin, is depleted in most patients with sickle cell
disease due to chronic haemolysis. Although single infusions of Hp can ameliorate
vaso-occlusion in mouse models of sickle cell disease, prior studies have not
examined the therapeutic benefits of more chronic Hp dosing on sickle cell
disease manifestations. In the present study, we explored the effect of Hp
treatment over a 3-month period in sickle mice at two dosing regimens: the first
at a moderate dose of 200 mg/kg thrice weekly and the second at a higher dose of
400 mg/kg thrice weekly. We found that only the higher dosing regimen resulted in
increased haem-oxygenase-1 and heavy chain ferritin (H-ferritin) expression and
decreased iron deposition in the kidney. Despite the decreased kidney iron
deposition following Hp treatment, there was no significant improvement in kidney
function. However, there was a nearly significant trend towards decreased liver
infarction.
PMID- 27507625
TI - The influence of the test setup on knee joint kinematics - A meta-analysis of
tibial rotation.
AB - The human knee is one of the most investigated joints in the human body. Various
test setups exist to measure and analyse knee kinematics in vitro which differ in
a wide range of parameters. The purpose of this article is to find an answer to
the question if the test setup influences the kinematic outcome of studies and to
what extend the results can be compared. To answer this question, we compared the
tibial rotation as a function of flexion angle presented in 19 published studies.
Raw data was extracted via image segmentation from the graphs depicted in these
publications and the differences between the publications was analysed.
Additionally, all test setups were compared regarding four aspects: method for
angle calculation, system for data acquisition, loading condition and testing rig
design. The resulting correlation matrix shows the influence of the test setup on
the study outcome. Our results indicate that each study needs to collect its own
reference data. Finally, we provide a mean internal rotation as a function of
flexion angle based on more than 140 specimens tested in 14 different studies.
PMID- 27507626
TI - Cost-effectiveness of Single- Versus Multistep Root Canal Treatment.
AB - INTRODUCTION: Single-visit root canal treatment requires fewer visits and reduces
treatment time and material use compared with multiple-visit treatment. However,
it might result in a higher risk of complications. We aimed to assess the long
term cost-effectiveness of single- versus multivisit root canal treatment using a
model-based approach. METHODS: A mixed public-private-payer perspective in German
health care was adopted. Permanent teeth were simulated over the lifetime of 40
year-old patients. Different tooth types and preoperative conditions were
modeled. Teeth could experience endodontic and nonendodontic complications. The
risk of endodontic complications after single- versus multiple-visit treatment
was estimated based on systematically collected data and adjusted depending on
the preoperative conditions. The health outcome was tooth retention time. Costs
were calculated based on the German dental fee catalogs and the Monte Carlo
microsimulations were performed for analysis. RESULTS: For nonvital molars
without periapical lesions, single-visit treatment was minimally less costly
(1703 Euro vs 1729 Euro) and more effective (19.9 vs 19.8 years) than multiple
visit treatment. This cost-effectiveness ranking also applied to vital molars or
those with periapical lesions. In single-rooted teeth, multiple-visit treatment
was less costly (1667 vs 1770 Euro) and more effective (18.9 vs 15.1 years).
CONCLUSIONS: The overall cost-effectiveness difference between treatments seems
limited. The resulting cost-effectiveness differs in subgroups of teeth, whereas
data supporting such subgroup analyses are scarce. Practical aspects in
scheduling treatments as well as patients' and dentists' preferences should be
considered for decision making.
PMID- 27507627
TI - Effect of Sodium Bicarbonate Buccal Infiltration on the Success of Inferior
Alveolar Nerve Block in Mandibular First Molars with Symptomatic Irreversible
Pulpitis: A Prospective, Randomized Double-blind Study.
AB - INTRODUCTION: The purpose of this prospective, randomized, double-blind study was
to evaluate the effect of a buccal infiltration of sodium bicarbonate on the
anesthetic success of the inferior alveolar nerve block (IANB) for mandibular
first molars in patients with symptomatic irreversible pulpitis. METHODS: One
hundred patients diagnosed with symptomatic irreversible pulpitis of a mandibular
first molar were selected. The patients randomly received a buccal infiltration
injection of either 0.7 mL 8.4% sodium bicarbonate with 0.3 mL 2% lidocaine
containing 1:80,000 epinephrine or 0.7 mL sterile distilled water with 0.3 mL 2%
lidocaine containing 1:80,000 epinephrine in a double-blind manner. After 15
minutes, all the patients received conventional IANB injection using 3.6 mL 2%
lidocaine with 1:80,000 epinephrine. Access cavity preparation was initiated 15
minutes after the IANB injection. Lip numbness was a requisite for all the
patients. Success was determined as no or mild pain on the basis of Heft-Parker
visual analog scale recordings upon access cavity preparation or initial
instrumentation. Data were analyzed using the t, chi-square and Mann-Whitney U
tests. RESULTS: The success rate after the buccal infiltration of sodium
bicarbonate was 78%, whereas without the buccal infiltration of sodium
bicarbonate it was 44% (P < .001). CONCLUSIONS: A buccal infiltration of 0.7 mL
8.4% sodium bicarbonate increased the success rate of IANBs in mandibular first
molars with symptomatic irreversible pulpitis.
PMID- 27507628
TI - The Assessment and Management of External Cervical Resorption with Periapical
Radiographs and Cone-beam Computed Tomography: A Clinical Study.
AB - INTRODUCTION: This in vivo study assessed whether there was a difference between
periapical radiographs (PRs) and cone-beam computed tomographic (CBCT) imaging in
the detection, assessment, and management of external cervical resorption (ECR).
The secondary aim was to determine if parallax radiographs were of any further
benefit compared with a single PR. METHODS: PR and CBCT data were gathered for
115 teeth (98 patients) consecutively diagnosed with ECR. The diagnosis and
treatment plan of each tooth were determined with PRs and CBCT imaging.
Sensitivity, specificity, positive predictive values, negative predictive values,
and receiver operator characteristic values were determined. RESULTS: The overall
sensitivity (0.86) and specificity (0.89) of PRs was significantly lower than
CBCT imaging (P < .001). PRs had a limited ability to accurately detect the size
(0.75), circumferential spread (0.60), and location of ECR compared with CBCT
imaging (P < .001). PRs also underestimated the size of the ECR lesion.
Significant differences (P < .001) were apparent in the treatment plans formed
when PRs were assessed versus CBCT imaging. Parallax radiographs were shown to be
of no additional benefit compared with a single radiograph. CONCLUSIONS: PRs have
significant limitations in the detection, assessment, and treatment planning of
ECR when compared with CBCT imaging. A CBCT scan should be considered before the
management of a potentially restorable ECR lesion.
PMID- 27507629
TI - Benefit from cytoreductive nephrectomy and the prognostic role of neutrophil-to
lymphocyte ratio in patients with metastatic renal cell carcinoma.
AB - BACKGROUND: The role of cytoreductive nephrectomy (CN) for metastatic renal cell
carcinoma (mRCC) in the era of targeted therapies is currently undefined. In
recent years, neutrophil-to-lymphocyte ratio (NLR) has emerged as a prognostic
marker in several cancers, including mRCC. In this multicentre retrospective
study, we aim to assess the impact of CN in mRCC and the value of NLR in risk
stratification and patient selection. METHODS: Retrospective data from patients
with de novo mRCC from four large Australian hospitals were collected. Survival
analyses were performed using the Kaplan-Meier method and compared using the log
rank test. Multivariate analyses were performed using the Cox proportional
hazards method. RESULTS: Our study identified 91 de novo mRCC patients. Patients
who underwent CN (n = 46, 51%) were more likely to be younger (59.0 years vs 64.6
years, P = 0.019) and to have received systemic therapy (91% vs 76%, P = 0.043).
Median overall survival (mOS) was significantly improved in patients who
underwent CN (23.0 months vs 10.9 months, hazard ratios (HR) 0.33, 95% confidence
interval (CI) 0.20-0.55, P < 0.0001). Patients with NLR >= 5 also had inferior
mOS (6.2 months vs 16.7 months, HR 1.94, 95% CI 1.14-3.29, P = 0.014). CN was
associated with substantially improved survival in patients with both NLR < 5
(mOS 31.1 months vs 7.0 months, HR 0.41, 95% CI, 0.18-0.64, P = 0.0009) and NLR
>= 5 (mOS 10.9 months vs 2.3 months, HR 0.33, 95% CI, 0.11-0.69, P = 0.009).
Significant survival benefits associated with CN were maintained in multivariate
analyses (HR 0.39, 95% CI 0.22-0.70, P = 0.0014). CONCLUSIONS: CN is associated
with significantly improved overall survival in de novo mRCC. The incremental
survival benefit associated with CN was seen irrespective of NLR.
PMID- 27507630
TI - Current Knowledge on Genetic Biofortification in Lentil.
AB - Micronutrient deficiency in the human body, popularly known as "hidden hunger",
causes many health problems. It presently affects >2 billion people worldwide,
especially in South Asia and sub-Saharan Africa. Biofortification of food crop
varieties is one way to combat the problem of hidden hunger using conventional
plant breeding and transgenic methods. Lentils are rich sources of protein,
micronutrients, and vitamins including iron, zinc, selenium, folates, and
carotenoids. Lentil genetic resources including germplasm and wild species showed
genetic variability for these traits. Studies revealed that a single serving of
lentils could provide a significant amount of the recommended daily allowance of
micronutrients and vitamins for adults. Therefore, lentils have been identified
as a food legume for biofortification, which could provide a whole food solution
to the global micronutrient malnutrition. The present review discusses the
current ongoing efforts toward genetic biofortification in lentils using
classical breeding and molecular marker-assisted approaches.
PMID- 27507631
TI - CD101, a novel echinocandin with exceptional stability properties and enhanced
aqueous solubility.
AB - : The echinocandins are an important class of antifungal agents. However,
instability and, in some cases, lack of solubility have restricted their use to
situations in which daily infusions are acceptable. CD101 is a novel echinocandin
in development for topical and weekly i.v. administration that exhibits prolonged
stability in plasma and aqueous solutions up to 40 degrees C. After incubation
for 44 h in rat, dog, monkey and human plasma at 37 degrees C, the percent of
CD101 remaining (91%, 79%, 94% and 93%, respectively) was consistently greater
than that of anidulafungin (7%, 15%, 14% and 7%, respectively). Similarly, after
incubation in phosphate-buffered saline at 37 degrees C, the CD101 remaining
(96%) was greater than that of anidulafungin (42%). CD101 exhibited <2%
degradation after long-term storage at 40 degrees C as a lyophilized powder (9
months) and at room temperature in 5% dextrose (15 months), 0.9% saline (12
months) and sterile water (18 months). Degradation was <7% at 40 degrees C in
acetate and lactate buffers (6 to 9 months at pH 4.5-5.5). The chemical stability
and solubility of CD101 contribute to dosing, pharmacokinetic, formulation and
safety advantages over other echinocandins and should expand utility beyond daily
i.v. THERAPY:
PMID- 27507632
TI - Germicidins H-J from Streptomyces sp. CB00361.
PMID- 27507633
TI - Allantopyrone A activates Keap1-Nrf2 pathway and protects PC12 cells from
oxidative stress-induced cell death.
AB - Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects
cells from oxidative stress through induction of various antioxidant enzymes. We
found by proteomic analysis that allantopyrone A, a metabolite isolated from an
endophytic fungus, upregulates the expression of proteins that are regulated by
the transcription factor Nrf2. Indeed, allantopyrone A increased the antioxidant
enzyme heme oxygenase-1 in PC12 cells. Moreover, it induced localization of Nrf2
in the nucleus. Affinity purification of allantopyrone A-binding protein showed
that this compound could bind directly to Keap1. Allantopyrone A suppressed
intracellular reactive oxygen species level and cell death induced by H2O2 in
PC12 cells. These results indicate that allantopyrone A protects PC12 cells from
oxidative stress-induced cell death through direct binding with Keap1 and
activation of the Keap1-Nrf2 pathway.
PMID- 27507634
TI - Feasibility of assessing patients' acceptable pain in a randomized controlled
trial on a patient pain education program.
AB - BACKGROUND: For patients with cancer-related pain, the numeric rating scale is
the most frequently used instrument to measure pain intensity. In the literature,
it has been suggested to interpret patient-reported ratings of pain in relation
to the pain intensity which is acceptable to the individual patient. AIM: We
aimed to examine the feasibility and course of acceptable pain intensity. DESIGN:
A secondary analysis of a randomized controlled trial that tested the
effectiveness of standard care versus standard care supplemented by a pain
consultation combined with a patient pain education program. SETTING: A total of
72 patients were included from an outpatient oncology clinic of a university
hospital. They were diagnosed with cancer-related nociceptive pain with an
average pain intensity ?4. RESULTS: Most patients (97%) were able to give a score
for acceptable pain. Almost half of the patients scored their acceptable pain in
the range of moderate to severe. Patients' ratings of acceptable pain were
stable; after 8 weeks, 69% of patients had a variation of up to 1 point compared
to baseline. However, the mean acceptable pain intensity remained equal in the
standard care group (from 4.6 (range: 0-8) to 5.0 (range: 2-8)) and decreased in
the intervention group (from 4.6 (range: 2-8) to 3.8 (range: 0-7, p < 0.01),
difference between groups p < 0.05). CONCLUSION: Measurement of acceptable pain
intensity is feasible. Patients with additional pain treatment became more
critical and accepted less pain. More research is needed before we can use
acceptable pain intensity as a reference for the interpretation of pain ratings.
PMID- 27507635
TI - Palliative homecare is associated with reduced high- and low-acuity emergency
department visits at the end of life: A population-based cohort study of cancer
decedents.
AB - BACKGROUND: Prior work shows that palliative homecare services reduce the
subsequent need for hospitalizations and emergency services; however, no study
has investigated whether this association is present for emergency department
visits of high acuity or whether it only applies to low-acuity emergency
department visits. AIM: To examine the association between palliative versus
standard homecare nursing and the rate of high-acuity and low-acuity emergency
department visits among cancer decedents during their last 6 months of life.
DESIGN: This is a retrospective cohort study of end-of-life homecare patients in
Ontario, Canada, who had confirmed cancer cause of death from 2004 to 2009. A
multivariable Poisson regression analysis was implemented to examine the
association between the receipt of palliative homecare nursing (vs standard
homecare nursing) and the rate of high- and low-acuity emergency department
visits, separately. RESULTS: There were 54,743 decedents who received homecare
nursing in the last 6 months of life. The receipt of palliative homecare nursing
decreased the rate of low-acuity emergency department visits (relative rate =
0.53, 95% confidence interval = 0.50-0.56) and was significantly associated with
a larger decrease in the rate of high-acuity emergency department visits
(relative rate = 0.37, 95% confidence interval = 0.35-0.38). CONCLUSION:
Receiving homecare nursing with palliative intent may decrease the need for dying
cancer patients to visit the emergency department, for both high and low-acuity
visits, compared to receiving general homecare nursing. Policy implications
include building support for additional training in palliative care to generalist
homecare nurses and increasing access to palliative homecare nursing.
PMID- 27507636
TI - Electronic palliative care coordination systems: Devising and testing a
methodology for evaluating documentation.
AB - BACKGROUND: The need to improve coordination of care at end of life has driven
electronic palliative care coordination systems implementation across the United
Kingdom and internationally. No approaches for evaluating electronic palliative
care coordination systems use in practice have been developed. AIM: This study
outlines and applies an evaluation framework for examining how and when
electronic documentation of advance care planning is occurring in end of life
care services. DESIGN: A pragmatic, formative process evaluation approach was
adopted. The evaluation drew on the Project Review and Objective Evaluation
methodology to guide the evaluation framework design, focusing on clinical
processes. SETTING/PARTICIPANTS: Data were extracted from electronic palliative
care coordination systems for 82 of 108 general practices across a large UK city.
All deaths ( n = 1229) recorded on electronic palliative care coordination
systems between April 2014 and March 2015 were included to determine the
proportion of all deaths recorded, median number of days prior to death that key
information was recorded and observations about routine data use. RESULTS: The
evaluation identified 26.8% of all deaths recorded on electronic palliative care
coordination systems. The median number of days to death was calculated for
initiation of an electronic palliative care coordination systems record (31
days), recording a patient's preferred place of death (8 days) and entry of Do
Not Attempt Cardiopulmonary Resuscitation decisions (34 days). Where preferred
and actual place of death was documented, these were matching for 75% of
patients. Anomalies were identified in coding used during data entry on
electronic palliative care coordination systems. CONCLUSION: This study reports
the first methodology for evaluating how and when electronic palliative care
coordination systems documentation is occurring. It raises questions about what
can be drawn from routine data collected through electronic palliative care
coordination systems and outlines considerations for future evaluation. Future
evaluations should consider work processes of health professionals using
electronic palliative care coordination systems.
PMID- 27507637
TI - The Edmonton Symptom Assessment Scale remains useful for depression screening.
PMID- 27507638
TI - Capsule Commentary on Battistone et al., "Mini-Residency" in Musculoskeletal
Care: a National Continuing Professional Development Program for Primary Care
Providers.
PMID- 27507639
TI - Development of an ELISA using anti-idiotypic antibody for diagnosis of
opisthorchiasis.
AB - Monoclonal antibody specific for an epitope of cretory-secretory antigen protein
of Opisthorchis felineus (Rivolta, 1884) (Trematoda: Opisthorchiidae) with a
molecular weight of 28 kDa was used in a sandwich enzyme-linked immunosorbent
assay (ELISA) for immobilisation of liver fluke specific antigen to the solid
phase. Examination of human sera by this ELISA compared with commercial assays
demonstrated that the monoclonal antibody epitope is located within this
significant parasite protein. Anti-idiotypic antibody specific for the paratope
of this monoclonal antibody was obtained by a hybridoma technique. Mimicking an
epitope of excretory-secretory antigen of O. felineus, it had the capacity to
bind specific antibody and elicit an antibody response. The value of anti
idiotypic antibody as a substitute for the liver fluke antigen was tested by
ELISA using serum samples of infected dogs. Anti-idiotypic antibody proved to be
of value in both an indirect-ELISA and a competitive-ELISA for diagnosis of
opisthorchiasis. Mature trematodes were isolated from all infected animals. The
faecal egg counts were negative in dogs with a relatively small number of
parasites, despite finding antibodies in serum by ELISA. Substitution of parasite
antigen with anti-idiotype avoids the use of experimental animals and also
reduces time-consuming steps of antigen preparation.
PMID- 27507640
TI - DNA-PkCS expression in oropharyngeal squamous cell carcinoma: Correlations with
human papillomavirus status and recurrence after transoral robotic surgery.
AB - BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal squamous cell
carcinoma (SCC) has improved clinical outcomes compared to HPV-negative disease.
However, the biology underlying differences in prognosis remains unclear.
METHODS: We characterized the expression of DNA-protein kinase catalytic subunit
(DNA-PkCS ), a key DNA repair protein also associated with tumor progression, in
29 cases of oropharyngeal SCCs and correlated our findings with HPV status and
disease recurrence. In addition, we assessed therapeutic response, migration, and
invasion in head and neck cancer cell lines upon DNA-PkCS knockdown. RESULTS: DNA
PkCS expression was significantly decreased in HPV-positive compared to HPV
negative oropharyngeal SCC samples. Within the HPV-positive subgroup, DNA-PkCS
expression was inversely related to HPV E6 and E7 expression and trended toward
significance as a predictor of recurrence. DNA-PkCS knockdown in cell lines
resulted in increased sensitivity to cisplatin and radiotherapy and reduced cell
migration and invasion. CONCLUSION: These results suggest DNA-PkCS should be
further studied as a potential marker of tumor progression in HPV-positive
oropharyngeal SCCs. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 206-214, 2017.
PMID- 27507641
TI - Quantifying App Store Dynamics: Longitudinal Tracking of Mental Health Apps.
AB - BACKGROUND: For many mental health conditions, mobile health apps offer the
ability to deliver information, support, and intervention outside the clinical
setting. However, there are difficulties with the use of a commercial app store
to distribute health care resources, including turnover of apps, irrelevance of
apps, and discordance with evidence-based practice. OBJECTIVE: The primary aim of
this study was to quantify the longevity and rate of turnover of mental health
apps within the official Android and iOS app stores. The secondary aim was to
quantify the proportion of apps that were clinically relevant and assess whether
the longevity of these apps differed from clinically nonrelevant apps. The
tertiary aim was to establish the proportion of clinically relevant apps that
included claims of clinical effectiveness. We performed additional subgroup
analyses using additional data from the app stores, including search result
ranking, user ratings, and number of downloads. METHODS: We searched iTunes (iOS)
and the Google Play (Android) app stores each day over a 9-month period for apps
related to depression, bipolar disorder, and suicide. We performed additional app
specific searches if an app no longer appeared within the main search RESULTS: On
the Android platform, 50% of the search results changed after 130 days
(depression), 195 days (bipolar disorder), and 115 days (suicide). Search results
were more stable on the iOS platform, with 50% of the search results remaining at
the end of the study period. Approximately 75% of Android and 90% of iOS apps
were still available to download at the end of the study. We identified only
35.3% (347/982) of apps as being clinically relevant for depression, of which 9
(2.6%) claimed clinical effectiveness. Only 3 included a full citation to a
published study. CONCLUSIONS: The mental health app environment is volatile, with
a clinically relevant app for depression becoming unavailable to download every
2.9 days. This poses challenges for consumers and clinicians seeking relevant and
long-term apps, as well as for researchers seeking to evaluate the evidence base
for publicly available apps.
PMID- 27507642
TI - Activation-induced cytidine deaminase selectively catalyzed active DNA
demethylation in pluripotency gene and improved cell reprogramming in bovine SCNT
embryo.
AB - DNA methylation in mammals is an epigenetic marker and necessary for normal
embryogenesis. The global genomic demethylation of 5-methylcytosine occurs during
the first cell cycle following fertilization. Activation-induced cytidine
deaminase (AID), which is well-known for the function in antibody
diversification, has been implicated to play a role in active demethylation, but
its role in cell reprogramming and its crosstalk with other DNA demethylation
mechanism need to be clarified. In this study, the dynamic epigenetic regulation
of cell pluripotency and embryo development by AID in bovine preimplantation
embryos was investigated. The analysis of an AID overexpressing transgenic cell
line showed that AID overexpression did not change the global genomic methylation
but did change the methylation status of the promoters of the OCT4, NANOG and
SOX2 genes, thereby causing changes in their expression. The siRNA-mediated AID
knockdown in early embryonic development indicated that AID interference did not
affect oocyte maturation or the following embryo development after in vitro
fertilization but influenced the DNA methylation status of OCT4 and NANOG. To
clarify the role of AID in preimplantation embryos, SCNT embryos were obtained
using AID-overexpressing cells as nuclear donors. Compared to the control group,
the cleavage and blastocyst rates were both significantly improved in the AID
overexpression group. The expression of OCT4 and NANOG was increased in the SCNT
embryos, whereas the methylation levels of their promoters were reduced. In
conclusion, this study demonstrated that AID selectively catalyzes DNA
demethylation of pluripotency genes to play a role in regulation their
expression, improves bovine SCNT embryo development by increased expression
levels.
PMID- 27507643
TI - Promoting differentiation of cultured myoblasts using biomimetic surfaces that
present alpha-laminin-2 peptides.
AB - Traditionally, muscle cell lines are cultured on glass coverslips and
differentiated to investigate myoblast fusion and differentiation. Efficient
differentiation of myoblasts produces a dense network of myotubes with the
correct organisation for contraction. Here we have tested the ability of
artificially generated, precisely controlled peptide surfaces to enhance the
efficiency of myoblast differentiation. We focused on specific short peptides
from alpha-laminin-2 (IKVSV, VQLRNGFPYFSY and GLLFYMARINHA) as well as residues
15-155 from FGF1. We tested if these peptides in isolation, and/or in combination
promoted muscle differentiation in culture, by promoting fusion and/or by
improving sarcomere organisation. The majority of these peptides promoted fusion
and differentiation in two different mouse myogenic cell lines and in primary
human myoblasts. The additive effects of all four peptides gave the best results
for both mouse cell lines tested, while primary human cell cultures
differentiated equally well on most peptide surfaces tested. These data show that
a mixture of short biomimetic peptides can reliably promote differentiation in
mouse and human myoblasts.
PMID- 27507644
TI - In silico analysis of novel mutations in maple syrup urine disease patients from
Iran.
AB - Maple Syrup Urine Disease (MSUD) is a rare autosomal recessive disorder of
branched-chain amino acid (BCAA) metabolism. The disease is mainly caused by
mutations either in the BCKDHA, BCKDHB, DBT or DLD genes encoding components of
the E1alpha, E1beta, E2 and E3 subunits of branched-chain alpha-keto acid
dehydrogenase complex (BCKDC), respectively. BCKDC is a mitochondrial enzyme
which is responsible for the normal breakdown of BCAA. The rate of consanguineous
marriage in Iran is 38.6 %, so the prevalence of autosomal recessive disorders is
higher in comparison to other countries. Consanguinity increases the chance of
the presence of pathogenic mutations in a homoallelic state. This phenomenon has
made homozygosity mapping a powerful tool for finding the probable causative gene
in heterogeneous disorders like IEM (Inborn Errors of Metabolism). In this study,
two sets of multiplex polymorphic STR (Short Tandem Repeat) markers linked to the
above-mentioned genes were selected to identify the probable pathogenic gene in
the studied families. The families who showed a homozygous haplotype for the STR
markers of the BCKDHB gene were subsequently sequenced. Four novel mutations
including c.633 + 1G > A, c.988G > A, c.833_834insCAC, and a homozygous deletion
of whole exon 3 c. (274 + 1_275-1) _(343 + 1_344-1), as well as one recently
reported (c. 508G > T) mutation have been identified. Interestingly, three
families shared a common haplotype structure along with the c. 508G > T mutation.
Also, four other families revealed another similar haplotype with c.988G > A
mutation. Founder effect can be a suggestive mechanism for the disease.
Additionally, structural models of MSUD mutations have been performed to predict
the pathogenesis of the newly identified variants.
PMID- 27507646
TI - Enteromyxum leei (Myxosporea: Bivalvulida) as the cause of myxosporean emaciation
disease of farmed olive flounders (Paralichthys olivaceus) and a turbot
(Scophthalmus maximus) on Jeju Island, Korea.
AB - A life-threatening emaciation disease of unknown cause(s) is affecting the
farming of olive flounders (Paralichthys olivaceus) and turbots (Scophthalmus
maximus) on Jeju Island, Korea. As this is one of the major industries in the
region, it is of great concern to local farmers trying to develop successful and
sustainable aquaculture. We examined 16 olive flounders and one turbot cultured
at three farms located in the southern part of Jeju Island, which manifested
moderate to severe emaciation such as thinning of the body with notable
appearance of bony ridges of the skull on heads. Fresh mucosal scrapings of the
intestinal mucosa contained many myxosporean vegetative stages at various
developments but not fully grown spores. Histological examination of
gastrointestinal and other visceral organs revealed striking changes in the
intestinal mucosa such as detachment and loss of the epithelium due to intensive
parasitism of the myxosporean vegetative stages, accompanied by considerable
leukocyte infiltration in the lamina propria, and at the final stage villus
atrophy with no epithelial lining. Specific polymerase chain reaction using a
pair of primers targeting a fragment of the 18S ribosomal RNA gene (rDNA) of
Enteromyxum leei, a known pathogen causing myxosporean emaciation disease in a
variety of cultured fish in Mediterranean countries and Japan, amplified 433-bp
products in almost all diseased fish samples, particularly the gastrointestinal
tract. Nearly the whole length of the 18S rDNA, 1672-bp long excluding primer
aligning sequences, of the present Korean isolate was comparable to those of E.
leei isolates from Japan and Europe, particularly those from the former region.
Taking the heavy load of various developmental stages of E. leei in the
gastrointestinal mucosa into account, we ascribe the emaciation disease of the
fish examined in the present study to this well-known myxosporean species and not
to another unknown pathogen(s).
PMID- 27507645
TI - Questionnaire survey on work motivations of gastrointestinal and hepatobiliary
pancreatic surgeons enrolled in a Japanese national interdisciplinary program.
AB - BACKGROUND: Among young residents, there seems to be a decreasing desire to
become surgeons, resulting in a decrease in the number of surgeons. There is
concern regarding a shortage of hepatobiliary pancreatic (HBP) surgery residents
in Japan. A questionnaire survey was designed to assess the work motivations of
Japanese gastrointestinal (GI) and HBP surgeons. METHODS: Questionnaires
assessing seven domains related to motivation (aptitude,
satisfaction/dissatisfaction, knowledge/skill, evaluation/approval, self
management, community/expectation from other parties, and emotion) were sent to
GI and HBP surgeons throughout Japan. Differences between HBP and GI surgeons
were analyzed. RESULTS: Responses were received from 27 institutions in Japan
between May and August 2014. Mid-career and senior HBP surgeons (11-20 years
after graduation) working in university hospitals were significantly less
satisfied with their work than GI surgeons (P = 0.036). Evaluation/approval
factors were significantly lower in senior HBP surgeons than in GI surgeons 16-20
years after graduation (P = 0.048). CONCLUSIONS: The future satisfaction of young
residents seeking to become HBP surgeons should be enhanced, providing an
appealing workplace for young residents and preventing discontinuation by mid
career and senior surgeons.
PMID- 27507647
TI - Characteristics of hepatocellular carcinoma in Egyptian patients with primary
Budd-Chiari syndrome.
AB - BACKGROUND & AIM: Budd-Chiari syndrome (BCS) is caused by hepatic venous outflow
obstruction. This work aimed at analyzing characteristics and factors associated
with development of hepatocellular carcinoma (HCC) in patients with primary BCS.
METHODS: A total of 348 Egyptian BCS patients were included. They were presented
to the Budd-Chiari Study Group of Ain Shams University Hospital. BCS was
confirmed using abdominal Doppler US. Abdominal magnetic resonance imaging (MRI),
MR venography and/or multislice computed tomography (CT) were performed to
confirm all diagnoses and to assess vascular anatomy. Hepatic focal lesions
detected during the study period (2005-2011) were evaluated using serum alpha
foetoprotein (AFP) level, imaging features and histopathological examination.
RESULTS: Diagnosis of HCC was confirmed in 15/348 patients (4.3%). Imaging
studies showed that 60% had multiple hepatic focal lesions ranging from 2 to 6.3
cm in size. The median level of serum AFP in BCS with HCC was 300 ng/mL vs 11
ng/mL in those without HCC (P<.001). A cut-off level >24.5 ng/mL for serum AFP
showed sensitivity 80%, specificity 97.9%, positive predictive value 93.18% and
negative predictive value 99.1% for detection of HCC in BCS patients. Male
gender, older age, cigarette smoking, serum AFP (>24.5 ng/mL) and shrunken liver
by ultrasonography were independent factors associated with HCC development.
CONCLUSION: Male gender, older age and cigarette smoking are independent risk
factors for development of HCC in BCS. Serum AFP is a good screening test in BCS.
PMID- 27507648
TI - Tissue-infiltrating mucosal-associated invariant T cells play an important role
against Mycobacterium tuberculosis infection in tuberculosis pleurisy.
AB - Control of infection with Mycobacterium tuberculosis (M.tb) requires effective
antigen-specific immune response, including CD4+ and CD8+ T-cell responses;
however, the local immune response of mucosal-associated invariant T (MAIT) cells
at the site of infection is unclear. MAIT cells are a prevalent and unique,
innate T-cell population that expresses the semi-invariant T-cell receptor
TCRValpha7.2. Our direct ex vivo analysis demonstrates that the frequency of MAIT
cells in pleural fluid was much higher than that in peripheral blood from healthy
donors, but much lower than that in peripheral blood from patients with
tuberculosis. M.tb-reactive MAIT cells highly expressed tissue-specific chemokine
receptors (CXCR3hiCXCR4hiCCR5hiCXCR6hi) and displayed an effector memory T-cell
phenotype (CD45RO+CCR7-CD62L-), which indicates preferential homing to mucosal
associated lymphoid tissues. Furthermore, the majority of MAIT cells in pleurisy
fluid express tissue-resident makers (CD69+) that were only marginally present on
MAIT cells from normal peripheral blood mononuclear cells. In addition, MAIT
cells produce cytokines IFN-gamma and TNF-alpha and exhibit cytotoxic activity
molecules, CD107a/b and granzyme B, in response to tuberculosis-specific
antigens, which suggests that MAIT cells played a significant role in immune
response to M.tb in local lesions. Here, we address the potential roles for M.tb
reactive MAIT cells at the site of tuberculosis infection.-Li, J., Yu, S., Zhang,
Y., Shen, J., Lao, S., Li, B., Yang, B., Wu, C. Tissue-infiltrating mucosal
associated invariant T cells play an important role against Mycobacterium
tuberculosis infection in tuberculosis pleurisy.
PMID- 27507650
TI - Long-term potentiation modulates synaptic phosphorylation networks and reshapes
the structure of the postsynaptic interactome.
AB - The postsynaptic site of neurons is composed of more than 1500 proteins arranged
in protein-protein interaction complexes, the composition of which is modulated
by protein phosphorylation through the actions of complex signaling networks.
Components of these networks function as key regulators of synaptic plasticity,
in particular hippocampal long-term potentiation (LTP). The postsynaptic density
(PSD) is a complex multicomponent structure that includes receptors, enzymes,
scaffold proteins, and structural proteins. We triggered LTP in the mouse
hippocampus CA1 region and then performed large-scale analyses to identify
phosphorylation-mediated events in the PSD and changes in the protein-protein
interactome of the PSD that were associated with LTP induction. Our data
indicated LTP-induced reorganization of the PSD. The dynamic reorganization of
the PSD links glutamate receptor signaling to kinases (writers) and phosphatases
(erasers), as well as the target proteins that are modulated by protein
phosphorylation and the proteins that recognize the phosphorylation status of
their binding partners (readers). Protein phosphorylation and protein interaction
networks converged at highly connected nodes within the PSD network. Furthermore,
the LTP-regulated phosphoproteins, which included the scaffold proteins Shank3,
Syngap1, Dlgap1, and Dlg4, represented the "PSD risk" for schizophrenia and
autism spectrum disorder, such that without these proteins in the analysis, the
association with the PSD and these two psychiatric diseases was not present.
These data are a rich resource for future studies of LTP and suggest that the PSD
holds the keys to understanding the molecular events that contribute to complex
neurological disorders that affect synaptic plasticity.
PMID- 27507651
TI - Comment on "SUMO deconjugation is required for arsenic-triggered ubiquitylation
of PML".
AB - Fasci et al proposed that a SENP1-mediated switch from SUMO2 to SUMO1 conjugation
on Lys(65) in promyelocytic leukemia protein (PML) is required for arsenic
induced PML degradation, the basis for the antileukemic activity of arsenic. We
found that PML or PML/RARA (retinoic acid receptor alpha) mutants that cannot be
SUMO-conjugated on this specific site nevertheless underwent immediate arsenic
triggered SUMO modification. Moreover, these mutants were efficiently degraded in
cells and even in vivo, demonstrating that SUMOylation of Lys(65) was dispensable
for arsenic response. The existence and putative role of a SUMO switch on PML
should thus be reassessed.
PMID- 27507652
TI - Response to Comment on "SUMO deconjugation is required for arsenic-triggered
ubiquitylation of PML".
AB - Arsenic trioxide chemotherapy cures acute promyelocytic leukemia by inducing the
ubiquitylation of an oncogenic fusion protein containing promyelocytic leukemia
protein (PML) subsequent to modification of PML by SUMO1 and SUMO2. We proposed
that the SUMO switch at Lys(65) of PML enhanced subsequent SUMO2 conjugation to
Lys(160) and consequent RNF4-dependent ubiquitylation of PML. Ferhi et al note
differences between their experimental system and ours regarding the outcome and
mechanisms of SUMO-dependent PML signaling. When confronted by apparently
contradictory data, it is appropriate to drill down to where the differences
could lie.
PMID- 27507649
TI - Histone deacetylase 3 supports endochondral bone formation by controlling
cytokine signaling and matrix remodeling.
AB - Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies
for some cancers and neurological disorders; however, each of these drugs
inhibits multiple HDACs and has detrimental effects on the skeleton. To better
understand how HDAC inhibitors affect endochondral bone formation, we
conditionally deleted one of their targets, Hdac3, pre- and postnatally in type
II collagen alpha1 (Col2alpha1)-expressing chondrocytes. Embryonic deletion was
lethal, but postnatal deletion of Hdac3 delayed secondary ossification center
formation, altered maturation of growth plate chondrocytes, and increased
osteoclast activity in the primary spongiosa. HDAC3-deficient chondrocytes
exhibited increased expression of cytokine and matrix-degrading genes (Il-6,
Mmp3, Mmp13, and Saa3) and a reduced abundance of genes related to extracellular
matrix production, bone development, and ossification (Acan, Col2a1, Ihh, and
Col10a1). Histone acetylation increased at and near genes that had increased
expression. The acetylation and activation of nuclear factor kappaB (NF-kappaB)
were also increased in HDAC3-deficient chondrocytes. Increased cytokine signaling
promoted autocrine activation of Janus kinase (JAK)-signal transducer and
activator of transcription (STAT) and NF-kappaB pathways to suppress chondrocyte
maturation, as well as paracrine activation of osteoclasts and bone resorption.
Blockade of interleukin-6 (IL-6)-JAK-STAT signaling, NF-kappaB signaling, and
bromodomain extraterminal proteins, which recognize acetylated lysines and
promote transcriptional elongation, significantly reduced Il-6 and Mmp13
expression in HDAC3-deficient chondrocytes and secondary activation in
osteoclasts. The JAK inhibitor ruxolitinib also reduced osteoclast activity in
Hdac3 conditional knockout mice. Thus, HDAC3 controls the temporal and spatial
expression of tissue-remodeling genes and inflammatory responses in chondrocytes
to ensure proper endochondral ossification during development.
PMID- 27507653
TI - Automated identification of antibiotic overdoses and adverse drug events via
analysis of prescribing alerts and medication administration records.
AB - Objectives: Electronic trigger detection tools hold promise to reduce Adverse
drug event (ADEs) through efficiencies of scale and real-time reporting. We
hypothesized that such a tool could automatically detect medication dosing errors
as well as manage and evaluate dosing rule modifications. Materials and Methods:
We created an order and alert analysis system that identified antibiotic
medication orders and evaluated user response to dosing alerts. Orders associated
with overridden alerts were examined for evidence of administration and the
delivered dose was compared to pharmacy-derived dosing rules to confirm true
overdoses. True overdose cases were reviewed for association with known ADEs.
Results: Of 55 546 orders reviewed, 539 were true overdose orders, which lead to
1965 known overdose administrations. Documentation of loose stools and diarrhea
was significantly increased following drug administration in the overdose group.
Dosing rule thresholds were altered to reflect clinically accurate dosing. These
rule changes decreased overall alert burden and improved the salience of alerts.
Discussion: Electronic algorithm-based detection systems can identify antibiotic
overdoses that are clinically relevant and are associated with known ADEs. The
system also serves as a platform for evaluating the effects of modifying
electronic dosing rules. These modifications lead to decreased alert burden and
improvements in response to decision support alerts. Conclusion: The success of
this test case suggests that gains are possible in reducing medication errors and
improving patient safety with automated algorithm-based detection systems. Follow
up studies will determine if the positive effects of the system persist and if
these changes lead to improved safety outcomes.
PMID- 27507655
TI - Proposed mechanism for reviewing the coverage of National Health Insurance
benefits: New mission for the National Health Insurance Committee.
PMID- 27507654
TI - Overexpression of Histone Deacetylase and Amyloid Precursor Protein in
Hepatocellular Carcinoma.
AB - Epigenetic modifications are involved in the pathogenesis of cancer, and histone
deacetylase inhibitors are considered potential therapeutic agents. Histone tails
undergo acetylation at lysine residues, which is associated with transcriptional
activation. However, previous studies indicated that as histone deacetylase
inhibitors, both (-)-epigallocatechin-3-gallate and valproic acid presented the
effects of downregulation of amyloid precursor protein expression, which resulted
in the induction of apoptosis. The downregulation of amyloid precursor protein,
instead of conventionally activating gene expression as histone deacetylase
inhibitor, was attractive. However, there was no relevant report on the
correlation of the expression of amyloid precursor protein and histone
deacetylase 1 in cancer. In the present study, we detected the expression of
amyloid precursor protein and histone deacetylase 1 in hepatocellular carcinoma
and adjacent tissues, as well as the correlations among histone deacetylase 1,
amyloid precursor protein, and tumor stage. The results showed that the
expressions of amyloid precursor protein and histone deacetylase 1 were
significantly higher in hepatocellular carcinoma tissues than that in adjacent
tissues ( P < .05), however, there was no statistical difference between amyloid
precursor protein and histone deacetylase 1 with tumor stages. The present
findings provided more foundation for the study on amyloid precursor protein
metabolism in cancer, especially on the regulation of amyloid precursor protein
by histone deacetylases.
PMID- 27507656
TI - Entropy analysis of stable isotopes in precipitation: tracing the monsoon systems
in China.
AB - Due to the complexity of monsoon systems and random behaviors of isotope tracers,
conventional methods are not adequate for uncovering detailed information about
monsoon activities from typically limited precipitation isotope data. We
developed a new approach based on the entropy theory to analyze such data with a
focus on the monsoon systems in China, dealing with the complexity of these
systems and data deficiency. Using precipitation isotope data from 42 selected
stations in and around China within the GNIP network, we computed entropies
associated with D and (18)O. These entropies were found to relate linearly to
each other with a proportionality factor close to unity. The spatial variations
of the D and (18)O entropy in the study area revealed the origins, extents and
pathways of the Chinese monsoon systems, as well as their interactions. While
further investigation is needed at a greater (global) scale, this study has
demonstrated how the entropy theory enables an in-depth analysis of precipitation
isotope data to trace the pathway and determine the range of a monsoon system.
PMID- 27507659
TI - Birth order and hospitalization for alcohol and narcotics use in Sweden.
AB - BACKGROUND: Previous studies have shown that birth order is an important
predictor of later life health as well as socioeconomic attainment. In this
study, we examine the relationship between birth order and hospitalization for
alcohol and narcotics use in Sweden. METHODS: We study the relationship between
birth order and hospitalization related to alcohol and narcotics use before and
after the age of 20 using Swedish register data for cohorts born 1987-1994. We
apply Cox proportional hazard models and use sibling fixed effects, eliminating
confounding by factors shared by the siblings. RESULTS: Before age 20 we find
that later born siblings are hospitalized for alcohol use at a higher rate than
first-borns, and there is a monotonic increase in the hazard of hospitalization
with increasing birth order. Second-borns are hospitalized at a rate 47% higher
than first-borns, and third-borns at a rate 65% higher. Similar patterns are
observed for hospitalization for narcotics use. After age 20 the pattern is
similar, but the association is weaker. These patterns are consistent across
various sibling group sizes. CONCLUSIONS: Later born siblings are more likely to
be hospitalized for both alcohol and narcotics use in Sweden. These birth order
effects are substantial in size, and larger than the estimated sex differences
for the risk of hospitalization related to alcohol and drug use before age 20,
and previous estimates for socioeconomic status differences in alcohol and drug
abuse.
PMID- 27507657
TI - What is abnormal about addiction-related attentional biases?
AB - BACKGROUND: The phenotype of addiction includes prominent attentional biases for
drug cues, which play a role in motivating drug-seeking behavior and contribute
to relapse. In a separate line of research, arbitrary stimuli have been shown to
automatically capture attention when previously associated with reward in non
clinical samples. METHODS AND RESULTS: Here, I argue that these two attentional
biases reflect the same cognitive process. I outline five characteristics that
exemplify attentional biases for drug cues: resistant to conflicting goals,
robust to extinction, linked to dorsal striatal dopamine and to biases in
approach behavior, and can distinguish between individuals with and without a
history of drug dependence. I then go on to describe how attentional biases for
arbitrary reward-associated stimuli share all of these features, and conclude by
arguing that the attentional components of addiction reflect a normal cognitive
process that promotes reward-seeking behavior.
PMID- 27507658
TI - Recognition and response to opioid overdose deaths-New Mexico, 2012.
AB - PURPOSE: Drug overdose deaths are epidemic in the U.S. Prescription opioid pain
relievers (OPR) and heroin account for the majority of drug overdoses. Preventing
death after an opioid overdose by naloxone administration requires the rapid
identification of the overdose by witnesses. This study used a state medical
examiner database to characterize fatal overdoses, evaluate witness-reported
signs of overdose, and identify opportunities for intervention. METHODS: We
reviewed all unintentional drug overdose deaths that occurred in New Mexico
during 2012. Data were abstracted from medical examiner records at the New Mexico
Office of the Medical Investigator. We compared mutually exclusive groups of OPR
and heroin-related deaths. RESULTS: Of the 489 overdose deaths reviewed, 49.3%
involved OPR, 21.7% involved heroin, 4.7% involved a mixture of OPR and heroin,
and 24.3% involved only non-opioid substances. The majority of OPR-related deaths
occurred in non-Hispanic whites (57.3%), men (58.5%), persons aged 40-59 years
(55.2%), and those with chronic medical conditions (89.2%). Most overdose deaths
occurred in the home (68.7%) and in the presence of bystanders (67.7%). OPR and
heroin deaths did not differ with respect to paramedic dispatch and CPR delivery,
however, heroin overdoses received naloxone twice as often (20.8% heroin vs.
10.0% OPR; p<0.01). CONCLUSION: OPR overdose deaths differed by age, health
status, and the presence of bystanders, yet received naloxone less often when
compared to heroin overdose deaths. These findings suggest that naloxone
education and distribution should be targeted in future prevention efforts.
PMID- 27507660
TI - Quantitative assays for measuring human telomerase activity and DNA binding
properties.
AB - Telomerase is the ribonucleoprotein enzyme that catalyzes the processive addition
of the telomeric DNA repeat 5'-TTAGGG-3' onto chromosome ends. In addition to its
fascinating biochemical and enzymatic properties, clinical interest in telomerase
stems from its dysregulated expression in ~90% of human cancers, representing a
broad spectrum of diseases. Exploiting telomerase as a therapeutic target and
hence identifying and/or evaluating potential inhibitors requires quantitative
measurement of its activity. This article presents procedures for measuring
multiple aspects of telomerase enzymology that are relevant to both fundamental
biochemistry and drug discovery: direct activity assays, DNA binding affinity,
DNA dissociation, and cell-based over-expression of the active enzyme complex.
PMID- 27507662
TI - Total synthesis of dehaloperophoramidine using a highly diastereoselective Hosomi
Sakurai reaction.
AB - The synthesis of dehaloperophoramidine, a non-halogenated derivative of the
marine natural product perophoramidine, and its biological activity towards
HCT116, HT29 and LoVo colorectal carcinoma cells is reported. A [3,3]-Claisen
rearrangement and an epoxide opening/allylsilylation reaction installed the
contiguous all-carbon quaternary stereocentres with the required relative
stereochemistry.
PMID- 27507661
TI - Association between rheumatoid arthritis and systemic mastocytosis: a case report
and literature review.
AB - Classically, mast cells (MC) are considered as important actors of the innate
immune response playing a pivotal role in IgE-mediated allergic and antiparasite
responses. In the last two decades, many experimental evidences demonstrated that
these hematopoietic-derived cells present in both connective and mucosal tissues
are also key modulators of the adaptive immune response and could contribute to
autoimmune disease notably in rheumatoid arthritis (RA). Recently, Bader-Meunier
et al. reported a series of 31 patients suffering from inflammatory joint
diseases associated with mastocytosis, suggesting that mastocytosis was
associated with a higher prevalence in spondyloarthritis. We discuss here the
possible link between chronic inflammatory arthritis and mastocytosis through the
report of a clinical case describing a patient developing RA after a long history
of mastocytosis. Of great interest, antihistamine treatment alone was sufficient
to treat RA in this patient.
PMID- 27507663
TI - A comparative analysis reveals the dosage sensitivity and regulatory patterns of
lncRNA in prostate cancer.
AB - Although the key roles of long non-coding RNAs (lncRNAs) in multiple diseases are
well documented, the relationship between the lncRNA copy number and expression
is unknown. Here, we present a comprehensive study that demonstrates the impact
of miRNA-TF co-regulatory motifs on the dosage effects of protein-coding genes
(PCGs) and lncRNAs in prostate cancer. By integrating copy number profiles,
expression profiles and regulatory relationships with miRNAs and transcription
factors, we reveal that lncRNAs and PCGs correlate with distinct dosage
sensitivity and regulatory pattern characteristics. We also show that lncRNAs
from different genomic regions have different features. Using a custom-built
framework, we identified 24 candidate prostate cancer-related lncRNAs based on
the known properties of established prostate-related lncRNAs. Our method will
enable the identification of cancer-related lncRNAs, which will provide new
insights into cancer lncRNA biology.
PMID- 27507664
TI - Alignment between values of dryland pastoralists and conservation needs for small
mammals.
AB - Policies for conservation outside protected areas, such as those designed to
address the decline in Australian mammals, will not result in net improvements
unless they address barriers to proenvironmental behavior. We used a mixed
methods approach to explore potential value-action gaps (disconnects between
values and subsequent action) for small mammal conservation behaviors among
pastoralists in dryland Australia. Using semistructured surveys and open-ended
interviews (n = 43), we explored values toward small mammals; uptake of a range
of current and intended actions that may provide benefit to small mammals; and
potential perceived barriers to their uptake. Pastoralists assigned great
conservation value to small mammals; over 80% (n = 36) agreed to strongly agreed
that small mammals on their property were important. These values did not
translate into stated willingness to engage in voluntary cessation of wild-dog
control (r2 = 0.187, p = 0.142, n = 43). However, assigning great conservation
value to small mammals was strongly related to stated voluntary willingness to
engage in the proenvironmental behavior most likely to result in benefits to
small mammals: cat and fox control (r2 = 0.558, p = 0.000, n = 43). There was no
significant difference between stated voluntarily and incentivized willingness to
engage in cat and fox control (p = 0.862, n = 43). The high levels of willingness
to engage in voluntary cat and fox control highlight a potential entry point for
addressing Australia's mammal declines because the engagement of pastoralists in
conservation programs targeting cat and fox control is unlikely to be prevented
by attitudinal constraints. Qualitative data suggest there is likely a
subpopulation of pastoralists who value small mammals but do not wish to engage
in formal conservation programs due to relational barriers with potential
implementers. A long-term commitment to engagement with pastoralists by
implementers will thus be necessary for conservation success. On-property cat and
fox control programs that build and leverage trust, shared goals, collaboration,
and shared learning experiences between stakeholders and that explicitly
recognize the complexity of small mammal dynamics and the property-level
ecological knowledge of pastoralists are more likely to gain traction.
PMID- 27507665
TI - Gradient moduli lens models: how material properties and application of forces
can affect deformation and distributions of stress.
AB - The human lens provides one-third of the ocular focussing power and is
responsible for altering focus over a range of distances. This ability, termed
accommodation, defines the process by which the lens alters shape to increase or
decrease ocular refractive power; this is mediated by the ciliary muscle through
the zonule. This ability decreases with age such that around the sixth decade of
life it is lost rendering the eye unable to focus on near objects. There are two
opponent theories that provide an explanation for the mechanism of accommodation;
definitive support for either of these requires investigation. This work aims to
elucidate how material properties can affect accommodation using Finite Element
models based on interferometric measurements of refractive index. Gradients of
moduli are created in three models from representative lenses, aged 16, 35 and 48
years. Different forms of zonular attachments are studied to determine which may
most closely mimic the physiological form by comparing stress and displacement
fields with simulated shape changes to accommodation in living lenses. The
results indicate that for models to mimic accommodation in living eyes, the
anterior and posterior parts of the zonule need independent force directions.
Choice of material properties affects which theory of accommodation is supported.
PMID- 27507666
TI - A highly sensitive HPLC-MS/MS method for quantification of 20(S)-protopanaxadiol
in human plasma and its application in phase IIa clinical trial of a novel
antidepressant agent.
AB - A highly sensitive HPLC-MS/MS assay method was established to quantify 20(S)
protopanaxadiol (PPD) in human plasma with dexamethasone as an internal standard.
The electrospray ion mass spectrometry (ESI-MS) was operated under the multiple
reactions monitoring mode (MRM) using positive ion mode. PPD was extracted from
500MUL plasma samples by liquid-liquid extraction then separated by a C18
analytical column with gradient elution. The concentration of PPD could be
determined by this HPLC-MS/MS method over the range of 0.05-20ng/mL with the
lower limit of quantification (LLOQ) of 0.05ng/mL. The method was successfully
applied to phase IIa clinical trial of Yuxintine (PPD capsule) in which plasma
samples of 87 subjects were analyzed following 6 weeks of oral administration of
placebo or PPD capsules in 5 different doses. In this study, the measured
concentration was linearly related to the oral dosage with R=0.9901. The minimum
and maximum values of measured concentration were 0.06 and 11.60ng/mL,
respectively. In addition, plasma concentrations of PPD in depression patients
were reported for the first time in our study.
PMID- 27507667
TI - An improvement of separation and response applying post-column compensation and
one-step acetone protein precipitation for the determination of coenzyme Q10 in
rat plasma by SFC-MS/MS.
AB - Coenzyme Q10 (CoQ10) solid dispersion was prepared to improve its oral
bioavailability due to the poor solubility of CoQ10. To evaluate the
pharmacokinetic behaviors of CoQ10 solid dispersion, a simple, rapid, sensitive
and environment friendly method for the determination of CoQ10 in rat plasma was
developed. In this study, samples were prepared by one-step protein precipitation
with acetone and then the supercritical fluid chromatography-electrospray
ionization tandem mass spectrometry (SFC-ESI-MS/MS) method was used. The
separation was achieved by an ACQUITY UPC(2)TM BEH 2-EP column (100mm*3mm,
1.7MUm) maintained at 35 degrees C, using carbon dioxide (>=99.99%) and methanol
(85:15, v/v) as the mobile phase at a flow rate of 1.0ml/min. To improve the
response and sensitivity, the compensation solvent of methanol with 2mM ammonium
acetate at a flow rate of 0.2ml/min was used and the total analysis time was only
1.5min for each sample. The detection was carried out on a tandem mass
spectrometer with electrospray ionization (ESI) source and the mass transition
ion pair was m/z 881.0->197.0 and 285.1->193.0 for CoQ10 and diazepam, internal
standard (IS), respectively. Calibration curve was linear over the concentration
range of 2.00-500.00ng/ml (r(2)>=0.998) with a lower limit of quantification of
2.00ng/ml. The intra- and inter-day accuracy and precision were below 15% for all
quality control samples. The proposed method was rapid, accurate and
reproducible, which was suitable to compare the pharmacokinetic behaviors in rats
after a single oral dose of 100mg/kg CoQ10 solid dispersion or tablets.
PMID- 27507668
TI - Multifunctional metal-polymer nanoagglomerates from single-pass aerosol self
assembly.
AB - In this study, gold (Au)-iron (Fe) nanoagglomerates were capped by a polymer
mixture (PM) consisting of poly(lactide-co-glycolic acid), protamine sulfate, and
poly-l-lysine via floating self-assembly in a single-pass aerosol configuration
as multibiofunctional nanoplatforms. The Au-Fe nanoagglomerates were directly
injected into PM droplets (PM dissolved in dichloromethane) in a collison
atomizer and subsequently heat-treated to liberate the solvent from the droplets,
resulting in the formation of PM-capped Au-Fe nanoagglomerates. Measured in
vitro, the cytotoxicities of the nanoagglomerates (>98.5% cell viability) showed
no significant differences compared with PM particles alone (>98.8%), thus
implying that the nanoagglomerates are suitable for further testing of
biofunctionalities. Measurements of gene delivery performance revealed that the
incorporation of the Au-Fe nanoagglomerates enhanced the gene delivery
performance (3.2 * 10(6) RLU mg(-1)) of the PM particles alone (2.1 * 10(6) RLU
mg(-1)), which may have been caused by the PM structural change from a spherical
to a hairy structure (i.e., the change followed the agglomerated backbone).
Combining the X-ray-absorbing ability of Au and the magnetic property of Fe led
to magnetic resonance (MR)-computed tomography (CT) contrast ability in a
phantom; and the signal intensities [which reached 64 s(-1) T2-relaxation in MR
and 194 Hounsfield units (HUs) in CT at 6.0 mg mL(-1)] depended on particle
concentration (0.5-6.0 mg mL(-1)).
PMID- 27507670
TI - A new function for the yeast trehalose-6P synthase (Tps1) protein, as key pro
survival factor during growth, chronological ageing, and apoptotic stress.
AB - Looking back to our recent work that challenged the paradigm of trehalose in
stress resistance in yeast, our objective was to revisit the role of this
disaccharide in chronological life span (CLS), and in the control of apoptosis.
Using a catalytically dead variant of the trehalose-6-phosphate synthase (Tps1)
protein, (the first enzyme in the trehalose biosynthetic pathway), and by
manipulating intracellular trehalose independently of this pathway, we
demonstrated that trehalose has no role in CLS or in the inhibition of acetic
acid or H202-triggered cell death. We showed instead that, in the absence of any
apoptotic stimulus, the Tps1 protein itself was necessary in preventing massive,
spontaneous commitment of yeast cells to apoptosis during growth. Without Tps1p,
the life span was shortened and cells were sensitized to acetic acid (AA) and
H202, whereas the overexpression of the inactive variant of Tps1p almost
abolished AA-triggered apoptosis. Genetic interaction analysis of TPS1 and genes
such as YCA1, NUC1 and AIF1 indicated that these key executioners of cell death
partially relayed tps1Delta-triggered signaling. Our results suggested that the
pro-survival role of Tps1p could be connected with its ability to preserve ATP
levels in yeast cells.
PMID- 27507669
TI - ER fatalities-The role of ER-mitochondrial contact sites in yeast life and death
decisions.
AB - Following extracellular stress signals, all eukaryotic cells choose whether to
elicit a pro-survival or pro-death response. The decision over which path to take
is governed by the severity and duration of the damage. In response to mild
stress, pro-survival programs are initiated (unfolded protein response,
autophagy, mitophagy) whereas severe or chronic stress forces the cell to abandon
these adaptive programs and shift towards regulated cell death to remove
irreversibly damaged cells. Both pro-survival and pro-death programs involve
regulated communication between the endoplasmic reticulum (ER) and mitochondria.
In yeast, recent data suggest this inter-organelle contact is facilitated by the
endoplasmic reticulum mitochondria encounter structure (ERMES). These membrane
contacts are not only important for the exchange of cellular signals, but also
play a role in mitochondrial tethering during mitophagy, mitochondrial fission
and mitochondrial inheritance. This review focuses on recent findings in yeast
that shed light on how ER-mitochondrial communication mediates critical cell fate
decisions.
PMID- 27507671
TI - Preoperative urinary tract obstruction in scoliosis patients.
AB - BACKGROUND: While the association between scoliosis and cardiac and respiratory
function impairments has been well characterized in clinical practice and
research, the potential effect of scoliosis on urinary tract structure and renal
function has received little attention. Therefore, the purpose of this study was
to evaluate the preoperative clinical characteristics of urinary tract structure
and renal function in pediatric patients with idiopathic scoliosis, using a
combination of blood tests, urinalysis, and imaging. METHODS: Preoperative
measures of urinary tract structure and renal function were obtained for 16
patients, 13-17 years old, scheduled for corrective surgery for idiopathic
scoliosis. Preoperative assessment included blood test and urinalysis, combined
with structural imaging on ultrasound (US), magnetic resonance imaging (MRI),
magnetic resonance urography (MRU), and radioisotope tracing (RI), using
technetium-99 m mercaptoacetyltriglycine (99m Tc-MAG3). Differences in blood and
urine tests between patients with and without urinary tract obstruction (UTO)
were evaluated for significance using Mann-Whitney U test. RESULTS: For all 16
patients, blood tests and MRU were within normal limits. Dilatation of the renal
pelvis was identified on US in eight patients (50.0%). UTO was identified on RI
in six patients (37.5%). UTO was associated with elevated beta2-microglobulin
concentration. Urinary beta2-microglobulin concentration >0.7 MUg/mg Cr
differentiated patients with UTO from those without UTO, with a sensitivity of
100% and specificity of 70%. CONCLUSIONS: beta2-Microglobulin concentration may
be a useful marker to screen for asymptomatic UTO in patients with idiopathic
scoliosis.
PMID- 27507672
TI - Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble
amyloid precursor protein and amyloid beta.
AB - Disturbed homocysteine metabolism may contribute to amyloidogenesis by modulating
the amyloid precursor protein (APP) production and processing. The objective of
this study was to investigate the relationships between cerebral amyloid
production and both blood and cerebrospinal fluid (CSF) markers of the
homocysteine metabolism. We assessed CSF concentrations of soluble APPalpha,
soluble APPbeta, and amyloid beta1-42 (Abeta1-42), as well as plasma levels of
homocysteine (Hcys), total vitamin B12, and folate, and CSF concentrations of
homocysteine (Hcys-CSF), 5-methyltetrahydrofolate (5-MTHF), S-adenosylmethionine
(SAM), and S-adenosylhomocysteine (SAH) in 59 subjects with normal cognition.
Linear regression analyses were performed to assess associations between
homocysteine metabolism parameters and amyloid production. The study was approved
by the Ethical Committee of the University of Bonn. After controlling for age,
gender, APOEe4 status, and albumin ratio (Qalb), higher Abeta1-42 CSF levels were
associated with high Hcys and low vitamin B12 plasma levels as well as with high
Hcys, high SAH, and low 5-MTHF CSF levels. Higher CSF concentrations of sAPPalpha
and sAPPbeta were associated with high SAH levels. The results suggest that
disturbed homocysteine metabolism is related to increased CSF levels of sAPP
forms and Abeta1-42, and may contribute to the accumulation of amyloid pathology
in the brain. Disturbed homocysteine metabolism may contribute to amyloidogenesis
by modulating the amyloid precursor protein (APP) production and processing. We
found associations between CSF levels of soluble APP forms and Abeta1-42, and
markers of the homocysteine metabolism in both plasma and CSF in adults with
normal cognition. Disturbed homocysteine metabolism may represent a target for
preventive and early disease-modifying interventions in Alzheimer's disease.
PMID- 27507673
TI - Polymorphism of the renalase gene in gestational diabetes mellitus.
AB - Renalase is considered as a novel candidate gene for type 2 diabetes. In this
study, we aimed to investigate the relationship of serum renalase and two single
nucleotide polymorphisms with gestational diabetes mellitus. One hundred and
ninety-eight normotensive pregnant females (n = 99 gestational diabetes mellitus;
n = 99 euglycemic pregnant controls) were classified according to the
International Association of the Diabetes and Pregnancy Study criteria. Fasting
and 2-h post glucose load blood levels and anthropometric assessment was
performed. Serum renalase was measured using enzyme-linked immunosorbent assay,
whereas DNA samples were genotyped for renalase single nucleotide polymorphisms
rs2576178 and rs10887800 using Polymerase chain reaction-Restriction fragment
length polymorphism method. In an age-matched case control study, no difference
was observed in the serum levels of renalase (p > 0.05). The variant rs10887800
showed an association with gestational diabetes mellitus and remained significant
after multiple adjustments (p < 0.05), whereas rs2576178 showed weak association
(p = 0.030) that was lost after multiple adjustments (p = 0.09). We inferred a
modest association of the rs10887800 polymorphism with gestational diabetes.
Although gestational diabetes mellitus is self-reversible, yet presence of this
minor G allele might predispose to metabolic syndrome phenotypes in near the
future.
PMID- 27507675
TI - Discordance Between Intraoperative Consultation by Frozen Section and Final
Diagnosis.
AB - Discrepancies between intraoperative consultations with frozen section diagnosis
and the final pathology report have the potential to alter treatment decisions
and affect patient care. Monitoring these correlations is a key component of
laboratory quality assurance, however identifying specific areas for improvement
can be difficult to attain. Our goal is to develop a standardized method
utilizing root cause analysis and a modified Eindhoven classification schematic
to identify the source of discrepancies and deferrals and subsequently to guide
performance improvement initiatives. A retrospective review of intraoperative
consultations performed at a tertiary level hospital and cancer center over a 6
month period identified deferrals and discrepancies between the intraoperative
consult report and the final pathology report. We developed and applied a
classification tool to identify the process errors and cognitive errors leading
to discrepant results. A total of 48 (4.6%) discrepancies and 24 (2.3%) deferrals
were identified from the 1042 frozen sections. Within the entire data set of
frozen sections, the process errors (n = 26, 54.2%) were due to gross sampling (n
= 16, 33.3%), histologic sampling (n = 8, 16.7%), and surgical sampling (n = 2,
4.2%). Interpretation errors (n = 22, 45.8%) included undercalls/false negatives
(n=8, 16.7%), overcalls/false positives (n = 10, 20.8%), and misclassification
errors (n = 4, 8.3%). Application of our classification tool demonstrated that
the root cause of discrepancies and deferrals varied both between organ systems
and by specific organs and that classification models may be utilized as a
standardized method to identify focused areas for improvement.
PMID- 27507674
TI - Initial experience with endocrinology e-consults.
PMID- 27507676
TI - Pregnenolone sulfate regulates prolactin production in the rat pituitary.
AB - Pregnenolone sulfate (PS) is a neuroactive steroid hormone produced in the brain.
In this study, the effects of PS on synthesis and secretion of rat pituitary
prolactin (PRL) were examined. To accomplish this, GH3 rat pituitary adenoma
cells were treated with PS, which showed significantly increased mRNA and protein
levels of PRL compared with the control. The mechanism of action responsible for
the effects of PS on PRL synthesis and secretion was investigated by pretreating
cells with inhibitors of traditional PRL- or the PS-related signaling pathway. PS
stimulated PRL transcription was significantly reduced by inhibitors of PKA, PKC
and MAPK, but unchanged by GABAAR and NMDAR inhibitors. Western blotting analysis
revealed that the total ERK1/2 level was upregulated in a time-dependent manner
following PS treatment. An approximate 10% increase in GH3 cell proliferation was
also observed in response to PS relative to the control. In the animal study,
levels of PRL in the pituitary and in serum were elevated by PS. PS-stimulated
PRL synthesis was also found to be associated with decreased expression of PRL
target genes such as GNRH1, FSHB and LHB. These findings show that PS upregulates
PRL synthesis and secretion in vivo and in vitro via MAPK signaling, suggesting
that it has the potential for use as a therapeutic hormone to treat PRL-related
disorders such as hypoprolactinemia and low milk supply.
PMID- 27507677
TI - Acceleration of wound healing by ultrasound activation of TiO2 in Escherichia
coli-infected wounds in mice.
AB - Surgical site infections continue to be a common complication affecting surgical
prognosis. Reactive oxygen species (ROS) are generated by ultrasound-irradiated
titanium dioxide (TiO2 ) (UIT). Although excessive ROS production can cause cell
damage, ROS at physiological levels mediate beneficial cellular responses,
including angiogenesis. This study investigated whether UIT can promote healing
of Escherichia coli-infected wounds. We used TiO2 and ultrasound irradiation
using an ultrasonography machine at a frequency of 1.0 MHz and intensity of 0.4 W
cm-2 . These levels are not bactericidal in vitro; therefore, we could study the
effect of UIT on E. coli survival without interference of ultrasound effects. The
number of cluster of differentiation 31-positive blood vessels, which are
indicative of angiogenesis, was decreased by bacterial infection, and increased
at the wound edges in the UIT-treated infected wounds, suggesting upregulation of
neovascularization by UIT. Although UIT treatment did not decrease E. coli
survival in vivo, it promoted healing of the infected wounds as evidenced by a
significant decrease in the wound area in the UIT-treated mice. Our findings
demonstrate that UIT promotes wound healing in surgical site infections and
suggest beneficial use of the UIT-based approach as a novel therapeutic method to
treat infected surgical wounds. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater
Res Part B: Appl Biomater, 105B: 2344-2351, 2017.
PMID- 27507679
TI - Cultural Attunement in Therapy With Mexican-Heritage Couples: A Grounded Theory
Analysis of Client and Therapist Experience.
AB - There is a need for culturally attuned approaches for couple therapy with
Mexican/Mexican-Americans. This qualitative grounded theory study utilized
interviews with 11 client couples of Mexican heritage and 14 marital and family
therapists to shed light on how Latino and non-Latino therapists co-construct
positive experiences of cultural attunement with Mexican and Mexican-American
couple clients. Analysis identified a model of cultural connection through
personal engagement with four interrelated phases: (a) mutual invitation, (b)
shared engagement, (c) expanding personal connection, and (d) creating cultural
connections. Clients in this study valued professionalism and expertise of the
therapist, but felt attuned to and respected when therapists demonstrated
humility, shared personal stories and emotion, and engaged in a collaborative
process.
PMID- 27507678
TI - Bridging the gap between guidelines and practice in the management of emerging
infectious diseases: a qualitative study of emergency nurses.
AB - AIMS AND OBJECTIVES: To explore the difficulties and strategies regarding
guideline implementation among emergency nurses. BACKGROUND: Emerging infectious
diseases remain an underlying source of global health concern. Guidelines for
accident and emergency departments would require adjustments for infectious
disease management. However, disparities between guidelines and nurses' practice
are frequently reported, which undermines the implementation of these guidelines
into practice. This article explores the experience of frontline emergency nurses
regarding guideline implementation and provides an in-depth account of their
strategies in bridging guideline-practice gaps. DESIGN: A qualitative descriptive
design was used. METHODS: Semi-structured, face-to-face, individual interviews
were conducted between November 2013-May 2014. A purposive sample of 12 frontline
emergency nurses from five accident and emergency departments in Hong Kong were
recruited. The audio-recorded interviews were transcribed verbatim and analysed
with a qualitative content analysis approach. RESULTS: Four key categories
associated with guideline-practice gaps emerged, including getting work done,
adapting to accelerated infection control measures, compromising care standards
and resolving competing clinical judgments across collaborating departments. The
results illustrate that the guideline-practice gaps could be associated with
inadequate provision of corresponding organisational supports after guidelines
are established. CONCLUSIONS: The nurses' experiences have uncovered the
difficulties in the implementation of guidelines in emergency care settings and
the corresponding strategies used to address these problems. The nurses'
experiences reflect their endeavour in adjusting accordingly and adapting
themselves to their circumstances in the face of unfeasible guidelines. RELEVANCE
TO CLINICAL PRACTICE: It is important to customise guidelines to the needs of
frontline nurses. Maintaining cross-departmental consensus on guideline
interpretation and operation is also indicated as an important component for
effective guideline implementation.
PMID- 27507681
TI - Metabolic pathways regulated by abscisic acid, salicylic acid and gamma
aminobutyric acid in association with improved drought tolerance in creeping
bentgrass (Agrostis stolonifera).
AB - Abscisic acid (ABA), salicylic acid (SA) and gamma-aminobutyric acid (GABA) are
known to play roles in regulating plant stress responses. This study was
conducted to determine metabolites and associated pathways regulated by ABA, SA
and GABA that could contribute to drought tolerance in creeping bentgrass
(Agrostis stolonifera). Plants were foliar sprayed with ABA (5 MUM), GABA (0.5
mM) and SA (10 MUM) or water (untreated control) prior to 25 days drought stress
in controlled growth chambers. Application of ABA, GABA or SA had similar
positive effects on alleviating drought damages, as manifested by the maintenance
of lower electrolyte leakage and greater relative water content in leaves of
treated plants relative to the untreated control. Metabolic profiling showed that
ABA, GABA and SA induced differential metabolic changes under drought stress. ABA
mainly promoted the accumulation of organic acids associated with tricarboxylic
acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA
strongly stimulated the accumulation of amino acids (proline, serine, threonine
and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA
enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5
oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids
(malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The
enhanced drought tolerance could be mainly due to the enhanced respiration
metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment
(OA) and energy metabolism by SA, and amino acid metabolism related to OA and
stress-defense secondary metabolism by GABA.
PMID- 27507680
TI - Detection of inflammatory cell function using (13)C magnetic resonance
spectroscopy of hyperpolarized [6-(13)C]-arginine.
AB - Myeloid-derived suppressor cells (MDSCs) are highly prevalent inflammatory cells
that play a key role in tumor development and are considered therapeutic targets.
MDSCs promote tumor growth by blocking T-cell-mediated anti-tumoral immune
response through depletion of arginine that is essential for T-cell
proliferation. To deplete arginine, MDSCs express high levels of arginase, which
catalyzes the breakdown of arginine into urea and ornithine. Here, we developed a
new hyperpolarized (13)C probe, [6-(13)C]-arginine, to image arginase activity.
We show that [6-(13)C]-arginine can be hyperpolarized, and hyperpolarized [(13)C]
urea production from [6-(13)C]-arginine is linearly correlated with arginase
concentration in vitro. Furthermore we show that we can detect a statistically
significant increase in hyperpolarized [(13)C]-urea production in MDSCs when
compared to control bone marrow cells. This increase was associated with an
increase in intracellular arginase concentration detected using a
spectrophotometric assay. Hyperpolarized [6-(13)C]-arginine could therefore serve
to image tumoral MDSC function and more broadly M2-like macrophages.
PMID- 27507682
TI - Receptor Antagonist of IL-13 Exerts a Potential Negative Regulation During Early
Infection of Human Schistosomiasis.
AB - The pathology of schistosomiasis is associated with the formation of granulomas,
and this process is associated with liver fibrosis. Studies indicate that Th1
cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in
the progression of fibrosis, and IL-13 has a critical role in this process. The
IL-13Ralpha2 receptor, known as a 'receptor antagonist' binds with high affinity
to IL-13, and studies have identified that this plays a part in reducing fibrosis
and the size of granulomas. The objective of this study was to evaluate the
function of IL-13Ralpha2 and cellular immune response in hepatic fibrosis. A
negative correlation between IL-13Ralpha2 and IL-13 was found, suggesting an
increase in cytokine in early fibrosis. Initially, a negative correlation between
IFN-gamma and IL-13 was found in patients without fibrosis, and subsequently,
this correlation was found to be positive in patients with severe fibrosis,
thereby highlighting a new mechanism for regulating the progress of periportal
fibrosis. There was a positive correlation between the profiles of Th1 and Th2
cytokines, suggesting the presence of both responses, thus regulating the
disease. The results contribute to a better understanding of the immune
mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in
humans.
PMID- 27507683
TI - Migratory Birds as Global Dispersal Vectors.
AB - Propagule dispersal beyond local scales has been considered rare and
unpredictable. However, for many plants, invertebrates, and microbes dispersed by
birds, long-distance dispersal (LDD) might be regularly achieved when mediated by
migratory movements. Because LDD operates over spatial extents spanning hundreds
to thousands of kilometers, it can promote rapid range shifts and determine
species distributions. We review evidence supporting this widespread LDD service
and propose a conceptual framework for estimating LDD by migratory birds.
Although further research and validation efforts are still needed, we show that
current knowledge can be used to make more realistic estimations of LDD mediated
by regular bird migrations, thus refining current predictions of its ecological
and evolutionary consequences.
PMID- 27507684
TI - Meeting the Self at the Crossroads: Thoughts on Aging as a Young Cancer Survivor.
AB - PURPOSE OF THE STUDY: With nearly 14.5 million cancer survivors currently alive
in the United States, it is expected this will rise to roughly 19 million by
2024. As more people will age with a history of cancer than ever before, it is
important to consider how experiences of cancer affect the life course through
the bending of time and its interpretation. As such, aging as a cancer survivor
must be at the forefront of health maintenance across the life course. DESIGN AND
METHODS: Through reference to my own cancer experiences in an auto-ethnographic
format, this article interprets the illness experience as co-occurring in a
young, aging body. This enhances our understanding of biographical reconstruction
and individual liminality through descriptions of wisdom imparted by the cancer
experience itself. Knowledge and wisdom are further interpreted as enhancing
researchers' understandings of cancer and cancer survivorship. RESULTS: In this
article, I use my illness experiences as a young person to describe evolving
interpretations of the life course, the aging body, and the self. IMPLICATIONS:
Concepts presented in this article aid researchers' understanding of how wisdom
might be achieved through the experience of protracted illness over time. Such
knowledge has important implications for the management of cancer as chronic,
which may be most clearly described through the lens of the ill person.
PMID- 27507685
TI - It's Interpersonal: Family Relationships, Genetic Risk, and Caregiving.
AB - My research program considers family relationships across the life course: in
early life, with a focus on disease prevention-leveraging genetic risk
information and relationships to motivate health-promoting behaviors-and in later
life, with a focus on informal caregiving-identifying characteristics of those
most vulnerable to, or resilient from, caregiver stress. It is fortuitous, if not
tragic, then, that my research and personal worlds collided during my mother's
final 8 months of life. Here, I discuss how this experience has shifted my
thinking within both arms of my research program. First, I consider the state of
the science in family health history, arguing that the current approach which
focuses on an individual's first- and second-degree relatives does not take us
far enough into the relational landscape to activate communal coping with disease
risk. Second, I discuss caregiving from a family systems perspective. My family's
experience confirmed the importance of using a systems approach and highlighted a
need to identify underlying variability in members' expectations of caregiving
roles. In so doing, I capture the significance of understanding the multiple
perspectives that frame a context in which families adapt and cope with risk and
disease diagnoses.
PMID- 27507686
TI - Reflections on Women's Retirement.
AB - Popular literature often claims that baby boom women will "redefine" retirement,
and there is some evidence in the gerontological literature that this may be
true. However, considerably more research needs to be done on this generation of
retirees. The author, a baby boomer herself, draws on recent research on
retirement and her own experiences in early retirement to examine what a "good
retirement" might mean, considering the diversity of baby boomers, the range of
their experiences, and their relationship to work.
PMID- 27507687
TI - Rationales for Anti-aging Activities in Middle Age: Aging, Health, or Appearance?
AB - Purpose: We explore the motivations of middle-aged consumers of anti-aging
products and services in relation to aging, health, and appearance. Admission of
use of anti-aging products and services could align a respondent with a
stigmatized group, old people, and also connotes a feminine concern with
aesthetics. For these reasons, people, particularly men, will be unlikely to
report using them for this purpose. Design and Methods: Semi-structured, in-depth
interviews were conducted among 19 men and women aged 42-61 years. Topics
included their perceptions of bodily changes and their responses to these. We
analyzed data qualitatively. Results: Respondents frame their uses of anti-aging
products in terms of health and appearance, not anti-aging per se. Both men and
women see anti-aging as related to beautiful appearance and thus as a feminized
activity. Both are concerned about appearance, but in gendered ways. Overall,
respondents conflate bodily appearance, health, and aging in their constructions
of anti-aging. Implications: This conflation maintains inequality by stigmatizing
old age as unhealthy and unseemly. Our results point to the limits of studying
the consumption of anti-aging products and services if researchers ask only about
anti-aging uses per se. They also point to the ways that discourses of health and
appearance naturalize ageism, as they suggest that old age inheres in bodies that
"naturally" decline and thus should be excluded.
PMID- 27507688
TI - New Love/Older Adults.
PMID- 27507689
TI - Diabetic ketoacidosis and severe hypertriglyceridaemia as a consequence of an
atypical antipsychotic agent.
AB - The atypical antipsychotic agent clozapine, although an effective treatment for
schizophrenia, is linked with metabolic adverse effects. We report a case of
diabetic ketoacidosis and very severe hypertriglyceridaemia associated with
clozapine use, in a patient with type 2 diabetes mellitus, who was successfully
treated with continuous insulin infusion and fluids. As clozapine proved to be
the most efficacious in controlling the patient's psychotic symptoms, the patient
has been continued on clozapine despite its known metabolic side effects.
Importantly the patient has achieved satisfactory long-term lipid and glycaemic
control. The current recommendations related to the metabolic care for patients
treated with atypical antipsychotic agents as well as the mechanisms behind
abnormal glucose and lipid regulation with clozapine therapy are discussed.
PMID- 27507690
TI - Isolated brain metastasis from a small renal mass.
AB - The identification of small renal masses is increasing. Active surveillance is a
guideline-approved management strategy for select patients with small renal
masses. Metastases during the observation of small renal masses are uncommon, and
no cases of brain metastasis have been reported. We report the case of a 73-year
old man who presented with tonic-clonic seizures as the result of a brain
metastasis from a small renal mass (3.5 cm in maximal dimension). Treatment with
whole brain radiotherapy was undertaken successfully. The patient will undergo
surveillance with consideration for systemic therapy at the time of progression.
PMID- 27507691
TI - Small cell neuroendocrine carcinoma of tracheostomy site in a patient with a
history of juvenile laryngeal papillomatosis.
AB - Juvenile laryngeal papillomatosis is the commonest cause of benign epithelial
tumours of the larynx. Following diagnostic biopsy, surgical debulking is the
mainstay of therapy. The condition is often recurrent with further papillomas
forming after debridement, requiring serial procedures and occasionally demanding
tracheostomy. Rarely, the disease can undergo malignant transformation; most
commonly to squamous cell carcinoma. We describe the first reported case of small
cell neuroendocrine carcinoma occurring in the previous tracheostomy site of a 29
year-old male with a history of juvenile laryngeal papillomatosis. The patient,
with a background of multiple treatments for juvenile papillomas, presented with
voice change, breathing difficultly and erythema at the site of previous
tracheostomy. Induction chemotherapy followed by chemoradiation was used to treat
the lesion with a good response to initial therapy.
PMID- 27507692
TI - Rare case of iridofundal coloboma with buried optic nerve head drusen in a
paediatric patient.
PMID- 27507693
TI - Meckel's diverticular perforation presenting as acute abdomen in the second
trimester of pregnancy.
AB - Meckel's diverticular perforation is a rare cause of acute abdomen during
pregnancy. We report the case of a 24-year-old woman at 24 weeks of gestation who
presented with abdominal pain for 4 days accompanied with abdominal distension,
tenderness and guarding in right lower quadrant. Ultrasonography was
inconclusive. The patient underwent exploratory laparotomy with the clinical
suspicion of appendicular perforation peritonitis. Intraoperatively, a perforated
Meckel's diverticulum was detected. Owing to gross contamination of the
peritoneal cavity, a diverticulectomy with ileostomy was performed. She had a
normal full-term vaginal delivery, and ileostomy was reversed 1 month after
delivery. The physiological and anatomical changes in pregnancy can make a
straightforward clinical diagnosis difficult. A high index of suspicion is
required to prevent delay in diagnosis and surgical intervention, which could
prove detrimental to the mother and fetus.
PMID- 27507694
TI - Calciphylaxis of the breast: a rare metabolic complication of kidney disease.
PMID- 27507695
TI - Pulmonary cavitary lesion and haemoptysis: rare aetiology on biopsy.
AB - Pleomorphic carcinoma of the lung is a rare form of malignancy that can present
similarly to other necrotising cavitary lung diseases. We present a case of a
Caucasian woman who presented with recurrent haemoptysis and a right upper lobe
cavitary lesion on CT scan. She underwent selective embolisation of the right
bronchial artery by interventional radiology to control her haemoptysis. Positron
emission tomography/CT scan was performed which showed significant
fluorodeoxyglucose uptake in the right upper lobe cavitary lesion. There was a
discussion among her providers about the aetiology of this lesion including
infection and malignancy. Cultures from bronchoalveolar lavage and blood were
negative for infection as the patient underwent right upper lobectomy which
showed invasive sarcomatoid pleomorphic carcinoma with a minor component of
acinar adenocarcinoma. She was diagnosed with stage IB (T2aN0M0) sarcomatoid
pleomorphic carcinoma and underwent adjuvant chemotherapy after her lobectomy
with recurrence and metastasis to her stomach and pancreas.
PMID- 27507696
TI - Asymptomatic posthaemodialysis femoral arteriovenous fistula: multidetector
computed tomography (MDCT) evaluation and management.
PMID- 27507697
TI - Annexin A10 is involved in the development and maintenance of neuropathic pain in
mice.
AB - ANXA10 (annexin A10) is a member of the annexin family, and its biological
effects are mediated primarily through the calcium-dependent phospholipid-binding
and calcium ion binding. We examined the gene expressions of the L5 spinal cord
after spinal nerve ligation (SNL)-induced neuropathic pain in mice by gene chip.
The results showed that Anxa10 mRNA was the most upregulated gene in annexin
family with 73.7-fold increase. Although previous studies have reported that
several annexins are involved in nociceptive pain, the role of Anxa10 in pain
remains undefined. We aimed to evaluate the role of ANXA10 in mediating injury
induced heat hyperalgesia and mechanical allodynia. We found that SNL induced
persistent upregulation of Anxa10 mRNA and protein in the spinal cord of mice.
Moreover, ANXA10 was colocalized with the neuronal marker MAP2 and astrocytic
marker glial fibrillary acidic protein (GFAP), but not with microglial marker
CD11b. Finally, pretreatment with Anxa10 siRNA partially prevented SNL-induced
mechanical allodynia and heat hyperalgesia. Posttreatment with Anxa10 siRNA
attenuated SNL-induced neuropathic pain. These findings suggest that ANXA10 might
be a novel target in the treatment of neuropathic pain.
PMID- 27507698
TI - Association between MKL1 rs6001946 and schizophrenia in a Han Chinese population.
AB - Megakaryoblastic leukemia 1 (MKL1) is highly expressed in the nervous system and
plays a potentially principal role in neuronal migration and morphology. A recent
study showed that some genetic loci within the MKL1 gene, especially single
nucleotide polymorphism (SNP) rs6001946, may increase schizophrenia
susceptibility. Here, we sought to determine whether the polymorphism rs6001946
was associated with schizophrenia in a Han Chinese population using the ligase
detection reaction-polymerase chain reaction method to genotype SNP rs6001946 in
the MKL1 gene. We observed that there was a marginally significant association
between SNP rs6001946 and the risk of schizophrenia (P=0.077). Our results
indicated that SNP rs6001946 of the MKL1 gene is likely a risk factor for
schizophrenia, but the role of SNP rs6001946 in the development of schizophrenia
in Han Chinese should be interpreted cautiously. Further studies with larger
sample sizes are needed to determine the involvement of the MKL1 polymorphism in
schizophrenia susceptibility.
PMID- 27507699
TI - Silencing strategies for therapy of SOD1-mediated ALS.
AB - Amyotrophic lateral sclerosis (ALS) is an adult-onset, lethal, paralytic disorder
caused by the degeneration of motor neurons. Our understanding of this disease
has been greatly facilitated by studies of familial ALS caused by mutations in
the gene encoding superoxide dismutase 1 (SOD1). Evidence indicates that
misfolded wild-type SOD1 may also be pathogenic in sporadic ALS. Mutant SOD1 is
neurotoxic through multiple mechanisms. Because the pathogenicity of mutant SOD1
is proportional to the dose of the toxic protein, a rational approach to treating
SOD1-related ALS is to reduce levels of the toxic SOD1 species. An advantage of
this strategy is that it potentially obviates intervening in multiple, downstream
pathological cascades. In recent years, several strategies to silence gene
expression have been developed. The most clinically promising are predicated on
approaches that enhance degradation of RNA, such as anti-sense oligonucleotides
(ASO) and RNA interference (RNAi); the latter include small inhibitory RNA
(siRNA), short hairpin RNA (shRNA) and microRNA (miR). Agents such as shRNA and
either native or synthetic miR are capable of permeating the central nervous
system (CNS) and efficiently silencing genes in the brain and spinal cord. Here
we review recent progress in silencing SOD1, focusing on studies using artificial
shRNA or miRNA in combination with potent viral vector delivery systems to
mediate SOD1 silencing within the CNS in transgenic SOD1G93A mice and non-human
primates.
PMID- 27507700
TI - Determination of Recent Growth Hormone Abuse Using a Single Dried Blood Spot.
AB - BACKGROUND: Although it is being increasingly applied, blood collection for drug
testing in sport presents some logistic issues that complicate full applicability
on a large scale. The use of dried blood spots (DBS) could benefit compliant
blood testing considerably owing to its simplicity, minimal invasiveness, analyte
stability, and reduced costs. The aim of this study was to evaluate the
applicability of DBS to the methodology approved by the World Anti-Doping Agency
(WADA) for detection of doping by recombinant human growth hormone (rhGH) in
serum. METHODS: A protocol for a single DBS analysis using the hGH isoforms
differential immunoassays (kit 1 and kit 2) was developed and validated. A
clinical study with healthy volunteers injected for 3 consecutive days with a low
subcutaneous dose (0.027 mg . kg(-1) . day(-1) . person(-1)) of rhGH was
conducted. Finger prick DBS and paired-time serum samples from arm venipuncture
were compared. RESULTS: The analysis of the DBS-based protocol indicated that
with only a single blood spot it was possible to detect positivity for growth
hormone abuse. In spite of the low rhGH dose administered and independently of
the kit used, the window of detection for DBS was confirmed in all analyzed
samples up to 8 h after rhGH administration and extended up to 12 h in 50% of the
cases. Serum positivity was detected in all studied samples for 12 h after
administration. CONCLUSIONS: These results support the usefulness of DBS as a
biological matrix for testing recent growth hormone abuse.
PMID- 27507701
TI - Genetic differentiation and population structure of five ethnic groups of Punjab
(North-West India).
AB - The state of Punjab in the North-West part of India has acted as the main passage
for all the major human invasions into the Indian subcontinent. It has resulted
in the mixing of foreign gene pool into the local populations, which led to an
extensive range of genetic diversity and has influenced the genetic structure of
populations in Punjab, North-West India. The present study was conducted to
examine the genetic structure, relationships, and extent of genetic
differentiation in five Indo-European speaking ethnic groups of Punjab. A total
of 1021 unrelated samples belonging to Banias, Brahmins, Jat Sikhs, Khatris, and
Scheduled castes were analyzed for four human-specific Ins/Del polymorphic loci
(ACE, APO, PLAT, and D1) and three restriction fragment length polymorphisms ESR
(PvuII), LPL (PvuII), and T2 (MspI) using Polymerase chain reaction (PCR). All
the loci were found to be polymorphic among the studied populations. The
frequency of the Alu insertion at APO locus was observed to exhibit the highest
value (82.6-96.3 %), whereas D1 exhibited the lowest (26.5-45.6 %) among all the
ethnic groups. The average heterozygosity among the studied populations ranged
from 0.3816 in Banias to 0.4163 in Khatris. The FST values ranged from 0.0418 to
0.0033 for the PLAT and LPL loci, respectively, with an average value being
0.0166. Phylogenetic analysis revealed that Banias and Khatris are genetically
closest to each other. The Jat Sikhs are genetically close to Brahmins and are
distant from the Banias. The Jat Sikhs, Banias, Brahmins, and Khatris are
genetically very distant from the Scheduled castes. Overall, Uniform allele
frequency distribution patterns, high average heterozygosity values, and a small
degree of genetic differentiation in this study suggest a genetic proximity among
the selected populations. A low level of genetic differentiation was observed in
the studied population groups indicating that genetic drift might have been small
or negligible in shaping the genetic structure of North-West Indian Populations.
PMID- 27507703
TI - Examining dynamics in a polymer matrix by single molecule fluorescence probes of
different sizes.
AB - Rotational motion of single fluorescence probes with different sizes doped inside
films of polyvinylacetate is investigated by defocused single molecule
fluorescence microscopy. Discrete vibration modes in the rotational motion of
individual probes are clearly exposed in the power spectra of the rotation
trajectories, reflecting multiple relaxation dynamics and also the difference in
dynamics among separate locations. The power spectra show a strong dependence on
the probe size and temperature. By sampling the rotation of a large number of
probes, the averaged power spectra show that the activated rotation of the probes
falls into the frequency range of the alpha-relaxation and data analysis shows
that activation of the vibration modes with all probes corresponds to the maximum
population of rotating probes, and this made the comparison between single
molecule data and the ensemble data meaningful (differential scanning
calorimetry, as an example). Such an analysis shows a coincidence between the
temperature of a significant occurrence of glass transition and the activation of
rotational motion of all probes with one specific size, indicating that such a
dimension correlates with the size of the cooperative rearrangement region - a
volume of approximately 1.0 nm(3).
PMID- 27507702
TI - Transcriptome sequencing and de novo characterization of Korean endemic land
snail, Koreanohadra kurodana for functional transcripts and SSR markers.
AB - The Korean endemic land snail Koreanohadra kurodana (Gastropoda: Bradybaenidae)
found in humid areas of broadleaf forests and shrubs have been considered
vulnerable as the number of individuals are declining in recent years. The
species is poorly characterized at the genomic level that limits the
understanding of functions at the molecular and genetics level. In the present
study, we performed de novo transcriptome sequencing to produce a comprehensive
transcript dataset of visceral mass tissue of K. kurodana by the Illumina paired
end sequencing technology. Over 234 million quality reads were assembled to a
total of 315,924 contigs and 191,071 unigenes, with an average and N50 length of
585.6 and 715 bp and 678 and 927 bp, respectively. Overall, 36.32 % of the
unigenes found matches to known protein/nucleotide sequences in the public
databases. The direction of the unigenes to functional categories was determined
using COG, GO, KEGG, and InterProScan protein domain search. The GO analysis
search resulted in 22,967 unigenes (12.02 %) being categorized into 40 functional
groups. The KEGG annotation revealed that metabolism pathway genes were enriched.
The most prominent protein motifs include the zinc finger, ribonuclease H,
reverse transcriptase, and ankyrin repeat domains. The simple sequence repeats
(SSRs) identified from >1 kb length of unigenes show a dominancy of dinucleotide
repeat motifs followed with tri- and tetranucleotide motifs. A number of unigenes
were putatively assessed to belong to adaptation and defense mechanisms including
heat shock proteins 70, Toll-like receptor 4, AMP-activated protein kinase,
aquaporin-2, etc. Our data provide a rich source for the identification and
functional characterization of new genes and candidate polymorphic SSR markers in
K. kurodana. The availability of transcriptome information (
http://bioinfo.sch.ac.kr/submission/ ) would promote the utilization of the
resources for phylogenetics study and genetic diversity assessment.
PMID- 27507704
TI - Prediction of kinase-specific phosphorylation sites through an integrative model
of protein context and sequence.
AB - Identifying kinase substrates and the specific phosphorylation sites they
regulate is an important factor in understanding protein function regulation and
signalling pathways. Computational prediction of kinase targets - assigning
kinases to putative substrates, and selecting from protein sequence the sites
that kinases can phosphorylate - requires the consideration of both the cellular
context that kinases operate in, as well as their binding affinity. This
consideration enables investigation of how phosphorylation influences a range of
biological processes. We report here a novel probabilistic model for classifying
kinase-specific phosphorylation sites from sequence across three model organisms:
human, mouse and yeast. The model incorporates position-specific amino acid
frequencies, and counts of co-occurring amino acids from kinase binding sites. We
show how this model can be seamlessly integrated with protein interactions and
cell-cycle abundance profiles. When evaluating the prediction accuracy of our
method, PhosphoPICK, on an independent hold-out set of kinase-specific
phosphorylation sites, it achieved an average specificity of 97%, with 32%
sensitivity. We compared PhosphoPICK's ability, through cross-validation, to
predict kinase-specific phosphorylation sites with alternative methods, and show
that at high levels of specificity PhosphoPICK obtains greater sensitivity for
most comparisons made. We investigated the relationship between kinase-specific
phosphorylation sites and nuclear localisation signals. We show that kinases PKA,
Akt1 and AurB have an over-representation of predicted binding sites at
particular positions downstream from predicted nuclear localisation signals,
demonstrating an important role for these kinases in regulating the nuclear
import of proteins. PhosphoPICK is freely available as a web-service at
http://bioinf.scmb.uq.edu.au/phosphopick.
PMID- 27507705
TI - Collaborative study for the calibration of replacement batches for the heparin
low-molecular-mass for assay biological reference preparation.
AB - The European Pharmacopoeia (Ph. Eur.) prescribes the control of the activity of
low molecular mass heparins by assays for anti-Xa and anti-IIa activities
(monograph 0828), using a reference standard calibrated in International Units
(IU). An international collaborative study coded BSP133 was launched in the
framework of the Biological Standardisation Programme (BSP) run under the aegis
of the Council of Europe and the European Commission to calibrate replacement
batches for the dwindling stocks of the Heparin low-molecular-mass for assay
Biological Reference Preparation (BRP) batch 8. Thirteen official medicines
control and manufacturers laboratories from European and non-European countries
took part in this study to calibrate two freeze-dried candidate batches against
the 3rd International Standard (IS) for heparin, low molecular weight (11/176;
3rd IS). The Heparin low-molecular-mass for assay BRP (batch 8) was also included
in the test panel to check the continuity between subsequent BRP batches. Taking
into account the stability data, the results of this collaborative study and on
the basis of the central statistical analysis performed at the European
Directorate for the Quality of Medicines & HealthCare (EDQM), the 2 candidate
batches were officially adopted by the Commission of the European Pharmacopoeia
as Heparin low-molecular-mass for assay BRP batches 9 and 10 with assigned anti
Xa activities of 102 and 100 IU/vial and anti-IIa activities of 34 and 33 IU/vial
respectively.
PMID- 27507706
TI - miRNA profiles in livers with different mass deficits after partial hepatectomy
and miR-106b~25 cluster accelerating hepatocyte proliferation in rats.
AB - Partial hepatectomy (PH) promotes the reentry of quiescent hepatocytes into cell
cycle for regrowth. miRNA profiles in livers with different mass deficits after
PH have not been investigated and miRNAs implicated in liver regeneration remain
unclear. We generated miRNA profiles from normal and remnant livers at 6, 12, 24,
and 36 hours after 1/3 or 2/3PH using microarrays. Compared with normal livers,
the proportion of altered miRNAs decreased with time after 1/3PH, but increased
after 2/3PH. Most of altered miRNAs between 1/3 and 2/3PH exhibited similar up-
or down-regulation, but lower expression magnitude for 1/3PH. Among
differentially expressed miRNAs between 2/3PH with robust DNA replication and
1/3PH with a minimal replicative response, we identified miR-101a, miR-92a, miR
25, miR-93 and miR-106b as key regulators of cell cycle. In 2/3PH model,
overexpression of miR-106b~25 cluster tended to accelerate liver regeneration,
while inhibition of miR-106b~25 cluster markedly repressed regenerative response
and delayed recovery of liver function. Mechanistically, RB1 and KAT2B with cell
cycle arrest activity were identified as novel targets of miR-106b/93 and miR-25,
respectively. Overall, we featured miRNA profiles and dynamics after 1/3 and
2/3PH, and identified miR-106b~25 cluster as being involved in timely cell cycle
entry of hepatocytes after PH.
PMID- 27507708
TI - Telemedicine for Gestational Diabetes Mellitus (TeleGDM): A Mixed-Method Study
Protocol of Effects of a Web-Based GDM Support System on Health Service
Utilization, Maternal and Fetal Outcomes, Costs, and User Experience.
AB - BACKGROUND: Women with insulin-treated gestational diabetes mellitus (GDM)
require close monitoring and support to manage their diabetes. Recent changes to
the diagnostic criteria have implications for service provision stemming from
increased prevalence, suggesting an increased burden on health services in the
future. Telemedicine may augment usual care and mitigate service burdens without
compromising clinical outcomes but evidence in GDM is limited. OBJECTIVE: The
Telemedicine for Gestational Diabetes Mellitus (TeleGDM) trial aims to explore
the use of telemedicine in supporting care and management of women with GDM
treated with insulin. METHODS: The TeleGDM is a mixed-methods study comprising an
exploratory randomized controlled trial (RCT) and a qualitative evaluation using
semistructured interviews. It involves women with insulin-treated GDM who are up
to 35 weeks gestation. Participating patients (n=100) are recruited face-to-face
in outpatient GDM clinics at an outer metropolitan tertiary hospital with a
culturally diverse catchment and a regional tertiary hospital. The second group
of participants (n=8) comprises Credentialed Diabetes Educator Registered Nurses
involved in routine care of the women with GDM at the participating clinics. The
RCT involves use of a Web-based patient-controlled personal health record for GDM
data sharing between patients and clinicians compared to usual care. Outcomes
include service utilization, maternal and fetal outcomes (eg, glycemic control,
2nd and 3rd trimester fetal size, type of delivery, baby birth weight), diabetes
self-efficacy, satisfaction, and costs. Semistructured interviews will be used to
examine user experiences and acceptability of telemedicine. RESULTS: The trial
recruitment is currently underway. Results are expected by the end of 2016 and
will be reported in a follow-up paper. CONCLUSIONS: Innovative use of technology
in supporting usual care delivery in women with GDM may facilitate timely access
to GDM monitoring data and mitigate care burdens without compromising maternal
and fetal outcomes. The intervention may potentially reduce health service
utilization. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
Registry (ANZCTR): ACTRN12614000934640;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366740 (Archived
by WebCite(r) at http://www.webcitation.org/6jRiqzjSv).
PMID- 27507707
TI - Microfabric Vessels for Embryoid Body Formation and Rapid Differentiation of
Pluripotent Stem Cells.
AB - Various scalable three-dimensional culture systems for regenerative medicine
using human induced pluripotent stem cells (hiPSCs) have been developed to date.
However, stable production of hiPSCs with homogeneous qualities still remains a
challenge. Here, we describe a novel and simple embryoid body (EB) formation
system using unique microfabricated culture vessels. Furthermore, this culture
system is useful for high throughput EB formation and rapid generation of
differentiated cells such as neural stem cells (NSCs) from hiPSCs. The period of
NSC differentiation was significantly shortened under high EB density culture
conditions. Simultaneous mass production of a pure population of NSCs was
possible within 4 days. These results indicate that the novel culture system
might not only become a unique tool to obtain new insights into developmental
biology based on human stem cells, but also provide an important tractable
platform for efficient and stable production of NSCs for clinical applications.
PMID- 27507709
TI - A morphological and genetic description of pentastomid infective nymphs belonging
to the family Sebekidae Sambon, 1922 in fish in Australian waters.
AB - Infective nymphal stages of the family Sebekidae Sambon, 1922 are reported from
four species of fish in Australian waters for the first time. Infected fish were
collected from locations in Western Australia, the Northern Territory and north
Queensland. The infective nymphs of Alofia merki Giglioli in Sambon, 1922 and
Sebekia purdieae Riley, Spratt et Winch, 1990 are reported and described for the
first time. The remaining specimens were identified as belonging to the genus
Sebekia Sambon, 1922 based on the combination of buccal cadre shape, shape and
size of hooks, and overall body size, but could not be attributed to any of the
other species of Sebekia already reported due to missing required morphological
features. DNA sequences of members of the family Sebekidae are presented for the
first time. The lack of knowledge on the pentastome fauna of wild crocodiles, and
any potential intermediate hosts, in northern Australia, is also outlined.
PMID- 27507710
TI - Recombinant overexpression of camel hepcidin cDNA in Pichia pastoris:
purification and characterization of the polyHis-tagged peptide HepcD-His.
AB - Hepcidin, a liver-expressed antimicrobial peptide, has been demonstrated to act
as an iron regulatory hormone as well as to exert a wide spectrum of
antimicrobial activity. The aim of this work was the expression, as secreted
peptide, purification, and characterization of a new recombinant polyHis-tagged
camel hepcidin (HepcD-His) in yeast Pichia pastoris. The use of this eukaryotic
expression system, for the production of HepcD-His, having 6 histidine residues
at its C terminus, was simpler and more efficient compared with the use of the
prokaryotic system Escherichia coli. Indeed, a single purification step was
required to isolate the soluble hepcidin with purity estimated more that 94% and
a yield of 2.8 against 0.2 mg/L for the E coli system. Matrix-assisted laser
desorption/ionization time-of-flight (TOF)/TOF mass spectrometry of the purified
HepcD-His showed 2 major peaks at m/z 4524.64 and 4634.56 corresponding to camel
hepcidin with 39 and 40 amino acids. Evaluation of disulfide bond connectivity
with the Ellman method showed an absence of free thiol groups, testifying that
the 8 cysteine residues in the peptide are displayed, forming 4 disulfide
bridges. Circular dichroism spectroscopy showed that camel hepcidin structure was
significantly modified at high temperature of 90 degrees C and returns to its
original structure when incubation temperature drops back to 20 degrees C.
Interestingly, this peptide showed also a greater bactericidal activity, at low
concentration of 9.5MUM, against E coli, than the synthetic analog DH3. Thus, the
production, at a large scale, of the recombinant camel hepcidin, HepcD-His, may
be helpful for future therapeutic applications including bacterial infection
diseases.
PMID- 27507711
TI - Worldwide impact of aerosol's time scale on the predicted long-term concentrating
solar power potential.
AB - Concentrating solar technologies, which are fuelled by the direct normal
component of solar irradiance (DNI), are among the most promising solar
technologies. Currently, the state-of the-art methods for DNI evaluation use
datasets of aerosol optical depth (AOD) with only coarse (typically monthly)
temporal resolution. Using daily AOD data from both site-specific observations at
ground stations as well as gridded model estimates, a methodology is developed to
evaluate how the calculated long-term DNI resource is affected by using AOD data
averaged over periods from 1 to 30 days. It is demonstrated here that the use of
monthly representations of AOD leads to systematic underestimations of the
predicted long-term DNI up to 10% in some areas with high solar resource, which
may result in detrimental consequences for the bankability of concentrating solar
power projects. Recommendations for the use of either daily or monthly AOD data
are provided on a geographical basis.
PMID- 27507712
TI - Survival outcomes in elderly patients with untreated upper aerodigestive tract
cancer.
AB - BACKGROUND: This study is an evaluation of survival in patients with upper
aerodigestive tract (UADT) cancer who did not receive guideline-directed therapy.
METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End
Results (SEER) database was examined to identify patients with invasive cancer of
the UADT. Patients were classified as "untreated" if they received neither
surgery nor radiotherapy. Kaplan-Meier observed survival estimates were computed
and stage-specific actuarial estimates of relative survival were computed.
RESULTS: Of 3589 untreated patients, 13.7% were black, compared to 9.5% white,
and 9.2% all other races (p <.0001). Patients with stage IV disease were more
likely to be untreated than those with stage I disease (11.9% vs 3.8%; p <.0001).
Median survival was 39 months for treated patients and 4 months for untreated
patients. CONCLUSION: The median survival for untreated patients was 4 months.
Stage, race, and primary site were independently associated with untreated
status. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 215-218, 2017.
PMID- 27507713
TI - Three-dimensional facial analysis of Chinese children with repaired unilateral
cleft lip and palate.
AB - We analyzed the facial features of Chinese children with repaired unilateral
cleft lip and palate (UCLP) and compared them with a normal control group using a
three-dimensional (3D) stereophotogrammetry camera. This cross-sectional study
examined 3D measurements of the facial surfaces of 20 Chinese children with
repaired UCLP and 40 unaffected Chinese children aged 7 to 12 years old, which
were captured using the VECTRA 3D five-pod photosystem and analyzed using Mirror
software. Twenty-five variables and two ratios were compared between both groups
using independent t-test. Intra- and inter-observer reliability was determined
using ten randomly selected images and analyzed using intra-class correlation
coefficient test (ICC). The level of significance was set at p < 0.0018. Intra-
and inter-observers' reliability was considered fair to excellent with an ICC
value ranging from 0.54 to 0.99. Statistically significant differences (p <
0.0018) were found mainly in the nasolabial region. The cleft group exhibited
wider alar base root width, flattened nose and broader nostril floor width on the
cleft side. They tended to have shorter upper lip length and thinner upper
vermillion thickness. Faces of Chinese children with repaired UCLP displayed
meaningful differences when compared to the normal group especially in the
nasolabial regions.
PMID- 27507715
TI - Randomized clinical trial of single-incision versus multiport laparoscopic
colectomy.
AB - BACKGROUND: The efficacy and safety of single-incision laparoscopic colectomy
(SILC) for colonic cancer remain unclear. The aim of this study was to determine
the outcomes of SILC compared with multiport laparoscopic colectomy (MPLC) for
colonic cancer. METHODS: Patients with histologically proven colonic carcinoma
located in the caecum, ascending, sigmoid or rectosigmoid colon, clinically
diagnosed as stage 0-III by CT, were eligible for this study. Patients were
randomized before surgery and underwent tumour dissection with complete mesocolic
excision. Safety analyses were conducted according to randomization groups.
RESULTS: A total of 200 patients were enrolled and randomized to the MPLC (100
patients) or SILC (100 patients) arm. Surgical outcomes were similar between the
MPLC and SILC arms, including duration of operation (mean 162 versus 156 min
respectively; P = 0.273), blood loss (mean 8.8 versus 21.4 ml; P = 0.102),
conversion to open laparotomy (2.0 versus 1.0 per cent; P = 0.561), reoperation
(3.0 versus 3.0 per cent; P = 1.000), time to first flatus (both median 1 day; P
= 0.155) and postoperative hospital stay (both median 6; P = 0.372). The total
skin incision length was significantly shorter in the SILC arm (mean 4.4 cm
versus 6.8 cm in the MPLC arm; P < 0.001). The median duration of analgesia use
was 5 days in the MPLC and 4 days in the SILC arm (P = 0.485). Overall
complication rates were equivalent (15.0 versus 12.0 per cent respecitvely; P =
0.680). CONCLUSION: SILC is not superior to MPLC. REGISTRATION NUMBER:
UMIN000007220 (http://www.umin.ac.jp/ctr/index.htm).
PMID- 27507716
TI - Making the next steps the right ones: progress towards the Smokefree Aotearoa
2025 Goal.
PMID- 27507714
TI - MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis.
AB - DNA double strand break (DSB) repair is critical for generation of B-cell
receptors, which are pre-requisite for B-cell progenitor survival. However, the
transcription factors that promote DSB repair in B cells are not known. Here we
show that MEF2C enhances the expression of DNA repair and recombination factors
in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell
survival. Although Mef2c-deficient mice maintain relatively intact peripheral B
lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery
after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active
regulatory regions with high-chromatin accessibility in DNA repair and V(D)J
genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in
pre-B cells reduces chromatin accessibility in multiple regulatory regions of the
MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by
ensuring proper expression of genes that encode DNA repair and B-cell factors.
PMID- 27507717
TI - Pregnant women lack accurate knowledge of their BMI and recommended weight gain
during pregnancy.
PMID- 27507718
TI - Smoking prevalence in New Zealand from 1996-2015: a critical review of national
data sources to inform progress toward the Smokefree 2025 goal.
AB - AIM: The New Zealand Government has committed to a goal of becoming a smokefree
nation by 2025. This study analysed recent smoking trends using three national
data sets to: i) assess progress towards the smokefree goal; and ii) critically
evaluate New Zealand's main national-level data sources on smoking prevalence for
measuring progress towards the Smokefree 2025 goal. METHODS: Trends in adult (age
15+) daily smoking prevalence from 1996 to 2015 were compiled from three data
sources: the New Zealand Census, the New Zealand Health Survey (NZHS), and the
Health and Lifestyles Survey (HLS). We compared key features of the surveys (eg,
sample size, ethnicity classification), examined composite trends across surveys,
and analysed differences between and within surveys over time. RESULTS: Both the
Census and the NZHS show a decline in adult (age 15+) daily smoking over the past
18 years, from 23-25% in 1996/97, to around 15% in 2014/15, with broadly
consistent findings from the HLS since it began in 2008. However, recent NZHS
findings do not suggest substantive reductions in daily smoking prevalence,
particularly for Maori and Pacific populations, with 2014/15 rates of 35.5% and
22.4% in these populations respectively, and no statistically significant change
since 2006/07. NZHS has advantages over the New Zealand Census and the HLS for
the purposes of monitoring annual progress towards to the Smokefree 2025 goal.
CONCLUSION: These data collectively suggest that recent declines in smoking
prevalence are modest and clearly inadequate for achieving the Smokefree 2025 and
interim 2018 goals, particularly for Maori and Pacific peoples. Continuation and
improvement of tobacco-related surveillance is crucial for monitoring progress
toward the 2025 goal.
PMID- 27507719
TI - The All New Zealand Acute Coronary Syndrome Quality Improvement Programme:
Implementation, Methodology and Cohorts (ANZACS-QI 9).
AB - The All New Zealand Acute Coronary Syndrome Quality Improvement programme (ANZACS
QI) uses a web-based system to create a clinical registry of patients with acute
coronary syndrome (ACS) and other cardiac problems admitted to hospitals across
New Zealand. This detailed clinical registry is complemented by parallel analyses
of, and individual linkage to, New Zealand's multiple routine health information
datasets. The programme is primarily designed to support secondary care
clinicians to implement evidence based guidelines and to meet national
performance targets for New Zealand cardiac patients. ANZACS-QI simultaneously
generates a large-scale research database and provides an electronic data
infrastructure for clinical registry studies. ANZACS-QI has been successfully
implemented in all the 41 public hospitals across New Zealand where acute cardiac
patients are admitted. By June 2015 25,273 patients with suspected ACS and 30,696
referred for coronary angiography were registered in ANZACS-QI. In this report we
describe the development and national implementation of ANZACS-QI, its
governance, the data collection processes and the current ANZACS-QI cohorts and
available outputs.
PMID- 27507720
TI - Pregnant women lack accurate knowledge of their BMI and recommended gestational
weight gain.
AB - AIM: To investigate pregnant women's knowledge of their body mass index (BMI) and
their knowledge of gestational weight gain guidelines. METHODS: Participants were
recruited when attending their nuchal translucency scan at between 11 and 13
weeks, 6-days gestation in Dunedin or Christchurch, New Zealand. Recruitment
staff measured participants' weight and height. By way of a self-administered,
paper-based survey, participants were asked to identify their body size
(including: underweight (BMI <18.5 kg/m2); normal weight (18.5-24.9); overweight
(25-29.9); and obese (>=30)), and recommended gestational weight gain (including
the 2009 Institute of Medicine guidelines for healthy weight gain in pregnancy,
along with the options: "I should not gain any weight in my pregnancy", plus "It
does not matter how much weight I gain"). Participant-measured BMI was compared
to responses for perceived BMI and recommended gestational weight gain to assess
accuracy. Demographic predictors of accuracy were also investigated. RESULTS: In
total, 644 women were included. Sixty-six percent of these correctly identified
their BMI category, however only 31% identified their correct gestational weight
gain recommendation. Overweight and obese women were much more likely to
underestimate their BMI than normal weight women (p<0.001 for both). Overweight
and obese women were also more likely to overestimate their weight gain
recommendation (OR=4, p<0.001; OR=18, p<0.001, respectively) while normal weight
women were more likely to underestimate their weight gain recommendation
(p<0.001). Independent of BMI, women of New Zealand European ethnicity were less
likely to underestimate their recommended gestational weight gain compared to
other women of non-Maori/non-Pacific Island ethnicity (p=0.001), whereas younger
women (p=0.012) were more likely to underestimate recommended gestational weight
gain. CONCLUSION: The present study indicates that New Zealand women,
particularly those who are overweight and obese, lack accurate knowledge of their
own body size, and this may lead to an under- or over-estimation of appropriate
gestational weight gain, which may in turn lead to increased risk of poor health
outcomes in pregnancy. Education strategies related to healthy weight gain in
pregnancy are urgently required.
PMID- 27507721
TI - Smoking in cars: knowledge, behaviours and support for smokefree cars legislation
among New Zealand smokers and recent quitters.
AB - AIM: Exposure to second-hand smoke (SHS) poses serious health consequences to non
smokers, and normalises smoking. Currently, there is no legislation restricting
smoking in private cars in New Zealand. This paper supplements previous New
Zealand studies on exposure to SHS in cars by examining smokers and recent
quitters' knowledge and behaviours towards smoking in cars, and their support for
two possible smokefree cars policy options. METHOD: The New Zealand Smoking
Monitor is a fortnightly survey that uses a self-refreshing panel approach. The
questionnaire contains smoking- and cessation-related questions, including eight
non-core questions addressing smoking in homes or cars. These questions were
answered by 364 respondents in 2014. Responses were compared by socio-demographic
variables and recent quit attempt status. RESULTS: Smoking in cars was common
among the respondents in our sample: 63% had recently smoked in a car when they
were the only person in it, and 27% had done so when there were other people
present. Some groups of respondents exhibited information gaps around the harms
(eg, compared with males, females had reduced odds of agreeing with the false
statement: "it's OK to smoke inside cars if there are windows open", OR=0.41,
0.21-0.78); however, support for banning smoking in cars if there are children in
them was consistently high across different sub-groups (92% overall). CONCLUSION:
Our data show the importance of providing specific information around the danger
of smoking in cars, and strategies to enforce a complete smokefree rule in cars.
Legislation may be required to further protect children from SHS exposure.
PMID- 27507722
TI - Improved scores for observed teamwork in the clinical environment following a
multidisciplinary operating room simulation intervention.
AB - AIMS: We ran a Multidisciplinary Operating Room Simulation (MORSim) course for 20
complete general surgical teams from two large metropolitan hospitals. Our goal
was to improve teamwork and communication in the operating room (OR). We
hypothesised that scores for teamwork and communication in the OR would improve
back in the workplace following MORSim. We used an extended Behavioural Marker
Risk Index (BMRI) to measure teamwork and communication, because a relationship
has previously been documented between BMRI scores and surgical patient outcomes.
METHODS: Trained observers scored general surgical teams in the OR at the two
study hospitals before and after MORSim, using the BMRI. RESULTS: Analysis of
BMRI scores for the 224 general surgical cases before and 213 cases after MORSim
showed BMRI scores improved by more than 20% (0.41 v 0.32, p<0.001). Previous
research suggests that this improved teamwork score would translate into a
clinically important reduction in complications and mortality in surgical
patients. CONCLUSIONS: We demonstrated an improvement in scores for teamwork and
communication in general surgical ORs following our intervention. These results
support the use of simulation-based multidisciplinary team training for OR staff
to promote better teamwork and communication, and potentially improve outcomes
for general surgical patients.
PMID- 27507723
TI - Key design features of a new smokefree law to help achieve the Smokefree
Aotearoa.
AB - AIM: To design new tobacco control legislation to achieve the New Zealand
Government's 2025 smokefree goal. METHOD: An original analysis of the legislative
options for New Zealand tobacco control. RESULTS: 'Business as usual' is most
unlikely to achieve smoking prevalence that is less than 5% by 2025. Key
components of a new Act would ideally include plans and targets with teeth, a
focus on the industry, a focus on the product, reduction of supply, and a whole
of-society approach to promote consistency in policy implementation through: i) a
public duty on government agencies to act consistently with smokefree law; ii) a
general duty on those associated with the tobacco/nicotine industry in relation
to tobacco control objectives; and iii) a principle requiring international
treaties to be interpreted consistently with tobacco control objectives.
CONCLUSION: Strategies such as those identified in this Viewpoint should be
explored further as part of urgently needed planning to achieve the New Zealand
Government's goal for Smokefree Aotearoa by 2025.
PMID- 27507724
TI - 'Poorly defined': unknown unknowns in New Zealand Rural Health.
AB - There is a considerable mismatch between the population that accesses rural
healthcare in New Zealand and the population defined as 'rural' using the current
statistics New Zealand rural and urban categorisations. Statistics New Zealand
definitions (based on population size or density) do not accurately identify the
population of New Zealanders who actually access rural health services. In fact,
around 40% of people who access rural health services are classified as 'urban'
under the Statistics New Zealand definition, while a further 20% of people who
are currently classified as 'rural' actually have ready access to urban health
services. Although there is some recognition that current definitions are
suboptimal, the extent of the uncertainty arising from these definitions is not
widely appreciated. This mismatch is sufficient to potentially undermine the
validity of both nationally-collated statistics and also any research undertaken
using Statistics New Zealand data. Under these circumstances it is not surprising
that the differences between rural and urban health care found in other countries
with similar health services have been difficult to demonstrate in New Zealand.
This article explains the extent of this mismatch and suggests how definitions of
rural might be improved to allow a better understanding of New Zealand rural
health.
PMID- 27507725
TI - Alcohol consumption by youth: Peers, parents, or prices?
AB - Using data from the National Longitudinal Survey of Adolescent to Adult Health,
we estimate the effect of peers' alcohol consumption and alcohol prices on the
drinking habits of high-school-age youth. We use the two-stage residual inclusion
method to account for the endogeneity of peer drinking in nonlinear models. For
our sample of high school students, we find that peer effects are statistically
and economically significant regarding the choice to participate in drinking but
are not significant for the frequency of drinking, including binge drinking.
Regarding alcohol prices, even though we have good price variation in our sample,
alcohol prices are not found to be significant. The results are important for
policymakers who are considering policies to reduce underage drinking, as we
conclude that no significant impact on underage drinking will result from low-tax
states' increasing excise taxes on alcohol so they are similar to those of high
tax states. Policymakers may choose to focus instead on the influence of peers
and changing the social norm behavior.
PMID- 27507726
TI - Automated multi-plug filtration cleanup for liquid chromatographic-tandem mass
spectrometric pesticide multi-residue analysis in representative crop
commodities.
AB - An automated multi-plug filtration cleanup (m-PFC) method on modified QuEChERS
(quick, easy, cheap, effective, rugged, and safe) extracts was developed. The
automatic device was aimed to reduce labor-consuming manual operation workload in
the cleanup steps. It could control the volume and the speed of pulling and
pushing cycles accurately. In this work, m-PFC was based on multi-walled carbon
nanotubes (MWCNTs) mixed with other sorbents and anhydrous magnesium sulfate
(MgSO4) in a packed tip for analysis of pesticide multi-residues in crop
commodities followed by liquid chromatography with tandem mass spectrometric (LC
MS/MS) detection. It was validated by analyzing 25 pesticides in six
representative matrices spiked at two concentration levels of 10 and 100MUg/kg.
Salts, sorbents, m-PFC procedure, automated pulling and pushing volume, automated
pulling speed, and pushing speed for each matrix were optimized. After
optimization, two general automated m-PFC methods were introduced to relatively
simple (apple, citrus fruit, peanut) and relatively complex (spinach, leek, green
tea) matrices. Spike recoveries were within 83 and 108% and 1-14% RSD for most
analytes in the tested matrices. Matrix-matched calibrations were performed with
the coefficients of determination >0.997 between concentration levels of 10 and
1000MUg/kg. The developed method was successfully applied to the determination of
pesticide residues in market samples.
PMID- 27507727
TI - Determination of pesticides in edible oils by liquid chromatography-tandem mass
spectrometry employing new generation materials for dispersive solid phase
extraction clean-up.
AB - The goal of this work was to evaluate the efficiency of several sorbents on
removal fats from edible oils (olive, soya and sunflower) during the clean-up
step for posterior determination of 165 pesticides by UHPLC-QqQ-MS/MS system. The
extraction procedure employed in this work was the citrate version of QuEChERS
method followed by a step of freezing out with dry ice and clean-up evaluation
using i) PSA with magnesium sulfate (d-SPE); ii) magnesium sulfate and Z-sep
sorbent (d-SPE); iii) Z-sep (column SPE) and iv) Agilent Bond Elut QuEChERS
Enhanced Matrix Removal-Lipid (EMR-Lipid). After evaluation of the recovery
results at 10, 20 and 50MUgkg(-1), the EMR-Lipid showed important advantages
comparing to the other sorbents evaluated, such as better recovery rates and
RSD%. The method was validated at the three concentrations described above.
Analytical curves linearity was evaluated by spiking blank oil samples at 10, 20,
50, 100 and 500MUgkg(-1). The method demonstrated good recoveries values between
the acceptable range of 70-120% and RSD%<20 for most of evaluated pesticides. In
order to evaluate the performance of the method, this same procedure was employed
to other oils such as soya and sunflower with very good results.
PMID- 27507728
TI - Dealing with the ubiquity of phthalates in the laboratory when determining
plasticizers by gas chromatography/mass spectrometry and PARAFAC.
AB - Determining plasticizers and other additives migrated from plastic materials
becomes a hard task when these substances are already present in the laboratory
environment. This work dealt with this drawback in the multiresidue determination
of four plasticizers (2,6-di-tert-butyl-4-methyl-phenol (BHT), diisobutyl
phthalate (DiBP), bis(2-ethylhexyl) adipate (DEHA) and diisononyl phthalate
(DiNP)) and a UV stabilizer (benzophenone (BP)) by gas chromatography/mass
spectrometry (GC/MS) using DiBP-d4 as internal standard. The ubiquity of DiBP by
a non-constant leaching process in the laboratory was detected, which could not
guarantee the achievement of a trustworthy quantification. To handle this, the
assessment of the level of DiBP in solvent blanks having fixed the probabilities
of false non-compliance (alpha) and false compliance (beta) at 0.01 was
performed. On the other hand, another special case was that of DiNP, in whose
chromatogram finger peaks appear because of an array of possible C9 isomers.
PARAFAC, used for the identification and quantification of all the substances, is
a useful chemometric tool that enabled a more reliable determination of this
analyte since no peak areas were considered but chromatographic and spectral
loadings. Since phthalates may migrate from rubber latex items, an evaluation of
the existence of matrix effects on the determination of the five analytes was
conducted prior to an extraction with hexane from a dummy for infants. As matrix
effects were present, the quantification of the compounds under study was
performed following the standard addition method using PARAFAC sample loadings as
response variable. As a result, the presence of BHT was confirmed, being its
concentration equal to 37.87MUgL(-1). Calibrations based on PARAFAC yielded the
following values for the decision limit (CCalpha): 1.16MUgL(-1) for BHT,
1.34MUgL(-1) for BP, 1.84MUgL(-1) for DEHA and 51.42MUgL(-1) for DiNP(for
alpha=0.05 and two replicates).
PMID- 27507729
TI - Magnetic solid-phase extraction using nanoporous three dimensional graphene
hybrid materials for high-capacity enrichment and simultaneous detection of nine
bisphenol analogs from water sample.
AB - The synthesis of a magnetic nanoporous three dimensional graphene (3DG)/ZnFe2O4
composite has been achieved. Through formation of graphene hydrogel, ZnFe2O4
magnetic particles was successfully introduced into the nanoporous 3DG, resulting
in a magnetic porous carbon material. The morphology, structure, and magnetic
behavior of the as-prepared 3DG/ZnFe2O4 were characterized by using the
techniques of SEM, XRD, BET, VSM, FTIR, Raman and TGA. The 3DG/ZnFe2O4 has a high
specific surface area and super paramagnetism. Its performance was evaluated by
the magnetic solid-phase extraction of nine bisphenol analogs (BPs) from water
samples followed by HPLC analysis, and showed excellent adsorption capability for
the nine target compounds. Under optimized condition, the lower method detection
limits (0.05-0.18ngmL(-1)), the higher enrichment factors (800 fold) and good
recoveries (95.1-103.8%) with relative standard deviation (RSD) values less than
6.2% were achieved. The results indicated that the developed method based on the
use of 3DG/ZnFe2O4 as the magnetic adsorbent has the advantages of convenience
and high efficiency, and can be successfully applied to detect the nine BPs in
real water samples.
PMID- 27507730
TI - Corrigendum to "In vitro cytotoxicity of Nicotiana gossei leaves, used in the
Australian Aboriginal smokeless tobacco known as pituri or mingkulpa" [Toxicol.
Lett. 254 (2016) 45-51].
PMID- 27507731
TI - Determining the efficacy of the chronic disease self-management programme and
readability of 'living a healthy life with chronic conditions' in a New Zealand
setting.
AB - BACKGROUND: Self-management programmes are an increasingly popular way of
treating chronic diseases. AIMS: This study aims to determine the efficacy of the
Stanford Chronic Disease Self-Management Programme (CDSMP) in a New Zealand
context by assessing course outcomes and readability of the accompanying
reference guide Living a Healthy Life with Chronic Conditions, 4th Edition.
METHODS: This is a cross-sectional pre-post study conducted in Auckland between
August 2009 and September 2015, using CDSMP participants' baseline and follow-up
Health Education Intervention Questionnaire (heiQTM ) data. Readability of the
guide was assessed using the Gunning Fog Index, Coleman Liau, Flesch Reading
Ease, Flesch Kincaid Grade Level and Simplified Measure of Gobbledygook scores.
RESULTS: Significant evidence of improvement (P <= 0.001) was observed in seven
of the eight domains measured by the heiQTM (Deakin University, Centre for
Population Health Research, Melbourne, Vic., Australia). The greatest
improvements were seen in skill and technique acquisition (mean change score
0.25, P <= 0.001) and self-monitoring and insight (0.18, P <= 0.001). There was
little evidence of improvement in health service navigation (0.04, P = 0.17).
Readability analyses indicate that a person needs to be reading at a minimum of
U.S. 8th grade level in order to understand the text, and possibly up to 11th
grade. CONCLUSIONS: The CDSMP is effective for improving patient self-efficacy in
the New Zealand setting. However, adaptation of the programme to support better
health service navigation is warranted. The readability of the reference guide is
not suitable for this setting and requires further improvement.
PMID- 27507732
TI - Survey of eye practitioners' preference of diagnostic tests and treatment
modalities for dry eye in Ghana.
AB - PURPOSE: This study sought to provide an evidence-based profile of the diagnosis,
treatment and knowledge or opinions on dry eye among optometrists and
ophthalmologists in Ghana. METHODS: This was a cross-sectional survey RESULTS:
The responses of 162 participants are included in the analysis. The most commonly
used test to diagnosed dry eye disease was tear break-up time followed by patient
history. The most common symptom doctors heard from dry eye patients were burning
sensation followed by foreign body sensation. The most often prescribed first-
line treatment for dry eye was aqueous-based artificial tears followed by lipid
based artificial tears. Most practitioners considered meibomian gland dysfunction
as the most common cause of dry eye followed by pterygium. The most often used
test to guide or gauge therapeutic effect is patient history followed closely by
tear break-up time. Most practitioners reported that 10%-20% of all their
patients they see in a day are diagnosed of dry eye. CONCLUSION: This study
showed tear break up time was the main test majority of practitioners in Ghana
used to diagnose dry eye but patient history was the main test used to gauge
therapeutic effect over time. Burning sensation was the commonest symptom
practitioners heard from dry eye patients whilst artificial tears was their main
and first-line treatment for dry eye.
PMID- 27507733
TI - Oral food challenge with a mixture of 'at risk' foods in children with FPIES.
PMID- 27507734
TI - Defective DNA repair increases susceptibility to senescence through extension of
Chk1-mediated G2 checkpoint activation.
AB - Susceptibility to senescence caused by defective DNA repair is a major hallmark
of progeroid syndrome patients, but molecular mechanisms of how defective DNA
repair predisposes to senescence are largely unknown. We demonstrate here that
suppression of DNA repair pathways extends the duration of Chk1-dependent G2
checkpoint activation and sensitizes cells to senescence through enhancement of
mitosis skipping. Extension of G2 checkpoint activation by introduction of the
TopBP1 activation domain and the nondegradable mutant of Claspin sensitizes cells
to senescence. In contrast, a shortening of G2 checkpoint activation by
expression of SIRT6 or depletion of OTUB2 reduces susceptibility to senescence.
Fibroblasts from progeroid syndromes tested shows a correlation between an
extension of G2 checkpoint activation and an increase in the susceptibility to
senescence. These results suggest that extension of G2 checkpoint activation
caused by defective DNA repair is critical for senescence predisposition in
progeroid syndrome patients.
PMID- 27507735
TI - Factors associated with Internet addiction: Cross-sectional study of Turkish
adolescents.
AB - BACKGROUND: The aim of this study was to investigate the prevalence of Internet
addiction (IA), and the relationship between sociodemographic characteristics,
depression, anxiety, attention-deficit-hyperactivity disorder (ADHD) symptoms and
IA in adolescents. METHODS: This was a cross-sectional school-based study with a
representative sample of 468 students aged 12-17 years at the first trimester of
the 2013-2014 academic year. The students were assessed using Young's Internet
Addiction Scale, Children's Depression Inventory, Beck Anxiety Inventory,
Conners' Parent Rating Scale, Conners' Teacher Rating Scale, Hollingshead-Redlich
Scale, and the information form including characteristics of Internet use and
socioeconomic status (SES). The relationship between these factors and Internet
use was examined. RESULTS: Approximately 1.6% of students were identified as
having IA, whereas 16.2% had possible IA. There were significant correlations
between IA and depression, anxiety, attention disorder and hyperactivity symptoms
in adolescents. Smoking was also related to IA. There was no significant
relationship between IA and age, sex, body mass index, school type, and SES.
CONCLUSIONS: Depression, anxiety, ADHD and smoking addiction are associated with
PIU in adolescent students. Preventive public health policies targeting the
psychological wellbeing of young people are needed.
PMID- 27507736
TI - Carotid Stenting Versus Carotid Endarterectomy: What Did the Carotid
Revascularization Endarterectomy Versus Stenting Trial Show and Where Do We Go
From Here?
AB - Although rapidly expanding in its use, carotid artery stenting remains a
relatively new procedure. Its growth is due, at least in part, to the perceived
advantages of a less invasive technique. However, the clinical effectiveness and
specific role for stenting in the treatment of carotid occlusive disease are
still under evaluation. The primary aim of the randomized clinical trial, Carotid
Revascularization Endarterectomy versus Stenting Trial (CREST), was to contrast
the relative efficacy of carotid stenting versus carotid endarterectomy in
preventing stroke, myocardial infarction, or death during a 30-day periprocedural
period or ipsilateral stroke over the follow-up period in patients with
symptomatic and asymptomatic extracranial carotid stenosis. The secondary goals
were to describe the differential efficacy of the 2 procedures in men and women,
contrast periprocedural (30-day) morbidity and postprocedural morbidity and
mortality, estimate and contrast the restenosis rates of the 2 procedures,
evaluate differences in measures of health-related quality of life and cost
effectiveness, and identify subgroups of participants at differential risk of
stenting or surgery. This report summarizes the results obtained from CREST with
respect to its primary and secondary aims.
PMID- 27507738
TI - Schizoxylon as an experimental model for studying interkingdom symbiosis.
AB - Experiments to re-synthesise lichens so far focused on co-cultures of fungal and
algal partners. However, recent studies have revealed that bacterial communities
colonise lichens in a stable and host-specific manner. We were therefore
interested in testing how lichenised fungi and algae interact with selected
bacteria in an experimental setup. We selected the symbiotic system of
Schizoxylon albescens and the algal genera Coccomyxa and Trebouxia as a suitable
model. We isolated bacterial strains from the naturally occurring bacterial
fraction of freshly collected specimens and established tripartite associations
under mixed culture experiments. The bacteria belong to Actinobacteria,
Firmicutes and Proteobacteria and corresponded to groups already found associated
with fungi including lichens. In mixed cultures with Coccomyxa, the fungus formed
a characteristic filamentous matrix and tightly contacted the algae; the bacteria
distributed in small patches between the algal cells and attached to the cell
walls. In mixed cultures with Trebouxia, the fungus did not develop the
filamentous matrix, but bacterial cells were observed to be tightly adhering to
the fungal hyphae. Our experiments show that this tripartite fungal-algal
bacterial model system can be maintained in culture and can offer multiple
opportunities for functional studies based on experiments under controlled
conditions in the laboratory.
PMID- 27507737
TI - Quiescent Bone Lining Cells Are a Major Source of Osteoblasts During Adulthood.
AB - The in vivo origin of bone-producing osteoblasts is not fully defined. Skeletal
stem cells, a population of mesenchymal stem cells resident in the bone marrow
compartment, are thought to act as osteoprogenitors during growth and adulthood.
Quiescent bone lining cells (BLCs) have been suggested as a population capable of
activation into mature osteoblasts. These cells were defined by location and
their morphology and studies addressing their significance have been hampered by
their inaccessibility, and lack of markers that would allow for their
identification and tracing. Using lineage tracing models, we have observed
labeled osteoblasts at time points extending beyond the reported lifespan for
this cell type, suggesting continuous reactivation of BLCs. BLCs also make a
major contribution to bone formation after osteoblast ablation, which includes
the ability to proliferate. In contrast, mesenchymal progenitors labeled by
Gremlin1 or alpha smooth muscle actin do not contribute to bone formation in this
setting. BLC activation is inhibited by glucocorticoids, which represent a well
established cause of osteoporosis. BLCs express cell surface markers
characteristic of mesenchymal stem/progenitors that are largely absent in
osteoblasts including Sca1 and Leptin Receptor. BLCs also show different gene
expression profiles to osteoblasts, including elevated expression of Mmp13, and
osteoclast regulators RANKL and macrophage colony stimulating factor, and retain
osteogenic potential upon transplantation. Our findings provide evidence that
bone lining cells represent a major source of osteoblasts during adulthood. Stem
Cells 2016;34:2930-2942.
PMID- 27507739
TI - Hydraulic fracturing offers view of microbial life in the deep terrestrial
subsurface.
AB - Horizontal drilling and hydraulic fracturing are increasingly used for recovering
energy resources in black shales across the globe. Although newly drilled wells
are providing access to rocks and fluids from kilometer depths to study the deep
biosphere, we have much to learn about microbial ecology of shales before and
after 'fracking'. Recent studies provide a framework for considering how
engineering activities alter this rock-hosted ecosystem. We first provide data on
the geochemical environment and microbial habitability in pristine shales. Next,
we summarize data showing the same pattern across fractured shales: diverse
assemblages of microbes are introduced into the subsurface, eventually converging
to a low diversity, halotolerant, bacterial and archaeal community. Data we
synthesized show that the shale microbial community predictably shifts in
response to temporal changes in geochemistry, favoring conservation of key
microorganisms regardless of inputs, shale location or operators. We identified
factors that constrain diversity in the shale and inhibit biodegradation at the
surface, including salinity, biocides, substrates and redox. Continued research
in this engineered ecosystem is required to assess additive biodegradability,
quantify infrastructure biocorrosion, treat wastewaters that return to the
surface and potentially enhance energy production through in situ methanogenesis.
PMID- 27507740
TI - Deep into the Aristolochia Flower: Expression of C, D, and E-Class Genes in
Aristolochia fimbriata (Aristolochiaceae).
AB - Aristolochia fimbriata (Aristolochiaceae) is a member of an early diverging
lineage of flowering plants and a promising candidate for evo-devo studies.
Aristolochia flowers exhibit a unique floral synorganization that consists of a
monosymmetric and petaloid calyx formed by three congenitally fused sepals, and a
gynostemium formed by the congenital fusion between stamens and the stigmatic
region of the carpels. This floral ground plan atypical in the magnoliids can be
used to evaluate the role of floral organ identity MADS-box genes during early
flower evolution. In this study, we present in situ hybridization experiments for
the homologs of the canonical C-, D-, and E-class genes. Spatiotemporal
expression of the C-class gene AfimAG is restricted to stamens, ovary, and
ovules, suggesting a conserved stamen and carpel identity function, consistent
with that reported in core-eudicots and monocots. The D-class gene AfimSTK is
detected in the anthers, the stigmas, the ovary, the ovules, the fruit, and the
seeds, suggesting conserved roles in ovule and seed identity and unique roles in
stamens, ovary, and fruit development. In addition, AfimSTK expression patterns
in areas of organ abscission and dehiscence zones suggest putative roles linked
to senescence processes. We found that both E-class genes are expressed in the
anthers and the ovary; however, AfimSEP2 exhibits higher expression compared to
AfimSEP1. These findings provide a comprehensive picture of the ancestral
expression patterns of the canonical MADS-box floral organ identity genes and the
foundations for further comparative analyses in other magnoliids.
PMID- 27507741
TI - Halting the Olympics-Zika virus bandwagon.
PMID- 27507742
TI - HPV vaccination: a decade on.
PMID- 27507743
TI - Evidence-based policy for salt reduction is needed.
PMID- 27507744
TI - End-of-life care across the world: a global moral failing.
PMID- 27507745
TI - Sitting on the FENSA: WHO engagement with industry.
PMID- 27507747
TI - The Zika virus public health emergency: 6 months on.
PMID- 27507748
TI - US presidential candidates far apart on environmental health.
PMID- 27507750
TI - Impact of proposal to extend charging for NHS in England.
PMID- 27507749
TI - UK surgical trainees will continue to support European research collaboration.
PMID- 27507751
TI - The need for global R&D coordination for infectious diseases with epidemic
potential.
PMID- 27507752
TI - A call for transparency in the evaluation of global maternal health projects.
PMID- 27507753
TI - The neglect of eating disorders.
PMID- 27507754
TI - The neglect of eating disorders - Authors' reply.
PMID- 27507755
TI - Preventing bloodstream infection in children: What's the CATCH?
PMID- 27507756
TI - Preventing bloodstream infection in children: What's the CATCH? - Authors' reply.
PMID- 27507758
TI - Department of Error.
PMID- 27507757
TI - Health diplomacy to tackle the crisis in Nepal.
PMID- 27507759
TI - An exploration of screening protocols for intimate partner violence in healthcare
facilities: a qualitative study.
AB - AIMS AND OBJECTIVES: Explore different methods by which intimate partner violence
screening practices are implemented in clinic and emergency settings and better
understand barriers and facilitators. BACKGROUND: Healthcare visits provide an
opportunity for providers to identify and provide assistance to victims of
intimate partner violence. However, wide variation exists in the implementation
of screening and response protocols. In addition, providers experience barriers
and facilitators to intimate partner violence screening and response. A
comprehensive understanding of these factors is necessary to improve the role
that providers play in detection and intervention of intimate partner violence.
DESIGN: Qualitative descriptive research design. METHODS: Sixteen healthcare
facilities were recruited from a large metropolitan area in the USA. Data were
collected through semi-structured, in-depth interviews with individuals
knowledgeable about intimate partner violence screening and response within their
facility. Data were analysed using directive content analysis. RESULTS: Major
themes and patterns concerning intimate partner violence screening and response
were identified within the following areas: procedural characteristics, barriers,
facilitators and additional needs. Patient-provider communication and
operational/facility characteristics emerged as critical aspects that impact the
successful implementation of intimate partner violence screening and response
programmes. Differences were found between clinic and emergency settings stemming
from variations in health delivery models. CONCLUSIONS: Results provide important
information on how healthcare facilities implement intimate partner violence
screening and response, suggestions for practice improvement and directions for
future interventions. Additional guidance is needed to ensure intimate partner
violence identification, and response procedures are effective and tailored to
needs of patients, providers and the facility. RELEVANCE TO CLINICAL PRACTICE:
Nurses are in a strategic position to play a pivotal role in identification of
and response to intimate partner violence. It is essential that nurses are
cognizant of this, and understand the actions they can take to assist patients
who have been victims of intimate partner violence. Recommendations on how to do
this are provided.
PMID- 27507760
TI - A Xhosa language translation of the CORE-OM using South African university
student samples.
AB - The translation of well established psychometric tools from English into Xhosa
may assist in improving access to psychological services for Xhosa speakers. The
aim of this study was to translate the Clinical Outcomes in Routine Evaluation -
Outcome Measure (CORE-OM), a measure of general distress and dysfunction
developed in the UK, into Xhosa for use at South African university student
counselling centres. The CORE-OM and embedded CORE-10 were translated into Xhosa
using a five-stage translation design. This design included (a) forward
translation, (b) back-translation, (c) committee approach, (d) qualitative
piloting, and (e) quantitative piloting on South African university students.
Clinical and general samples were drawn from English-medium South African
universities. Clinical samples were generated from university student counselling
centres. General student samples were generated through random stratified cluster
sampling of full-time university students. Qualitative feedback from the
translation process and results from quantitative piloting of the 34-item CORE-OM
English and Xhosa versions supported the reduction of the scale to 10 items. This
reduced scale is referred to as the South African CORE-10 (SA CORE-10). A
measurement and structural model of the SA CORE-10 English version was developed
and cross-validated using an English-speaking university student sample.
Equivalence of this model with the SA CORE-10 Xhosa version was investigated
using a first-language Xhosa-speaking university sample. Partial measurement
equivalence was achieved at the metric level. The resultant SA CORE-10 Xhosa and
English versions provide core measures of distress and dysfunction. Additional,
culture- and language-specific domains could be added to increase sensitivity and
specificity.
PMID- 27507761
TI - Contextualizing Afghan refugee views of depression through narratives of trauma,
resettlement stress, and coping.
AB - This qualitative study explored how Afghan refugees conceptualize frames of mind
that may reflect depression in general and as it relates to trauma they
experienced. We performed in-depth interviews with 18 Afghans residing in the San
Diego area. Views regarding the causes, symptoms, and perceived treatments of
depression were gathered through free-listing techniques, and supplemented with
narratives relating to pre- and post-resettlement stressors and coping
mechanisms. Data were analyzed with standard qualitative content analysis
methods. Items endorsed with relation to depression causality included pre
migration war traumas, notably separation from family, and post-migration
stressors including status dissonance and cultural conflicts that ranged from
linguistic challenges to intergenerational problems. Depressive symptoms were
viewed as highly debilitating, and included changes in temperament, altered
cognitions, avoidance and dissociative behaviors, and somatic complaints. Relief
was sought through family reunification and community support, reliance on
prayer, and the academic success of their children in the US. The findings
underscore the need for practitioners to take into account situational stressors,
cultural aspects of mourning and symptomatology, and existing coping mechanisms
in developing interventions that are based on refugees' articulated needs.
PMID- 27507762
TI - Connection of the Posterior Occipital Muscle and Dura Mater of the Siamese
Crocodile.
AB - The myodural bridge was proposed initially in 1995. The myodural bridge is a
connective tissue bridge that connects a pair of deep muscles at the suboccipital
region to the dura mater. There have been numerous studies concerning the
morphology and function of the myodural bridge. To determine whether a myodural
bridge exists in reptiles, six Siamese crocodiles were investigated using gross
anatomy dissection and P45 sheet plastination technologies. As a result, we
demonstrated that the posterior occipital muscles of the Siamese crocodile are
directly or indirectly connected to the proatlas, atlas, and intermembrane
between them. Multiple trabeculae existing in the posterior epidural space
extended from the ventral surface of the proatlas, atlas, and intermembrane
between them to the dorsal surface of the spinal dura mater. This study showed
that the posterior occipital muscle in the suboccipital region of the Siamese
crocodile is connected to the spinal dura mater through the proatlas, atlas, and
the trabeculae. In conclusion, a myodural bridge-like structure exists in
reptiles. This connection may act as a pump to provide cerebrospinal fluid (CSF)
circulation at the occipitocervical junction. We hypothesize that a physiologic
role of the Siamese crocodile's myodural bridge may be analogous to the human
myodural bridge. Anat Rec, 299:1402-1408, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27507763
TI - Inhibition of VEGF165/VEGFR2-dependent signaling by LECT2 suppresses
hepatocellular carcinoma angiogenesis.
AB - Hepatocellular carcinoma (HCC) relies on angiogenesis for growth and metastasis.
Leukocyte cell-derived chemotaxin 2 (LECT2) is a cytokine and preferentially
expressed in the liver. Previous studies have found that LECT2 targets to both
immune and tumor cells to suppress HCC development and vascular invasion.
Although LECT2 did not affect HCC cells growth in vitro, it still suppressed HCC
xenografts growth in immune-deficient mice, suggesting other cells such as stroma
cells may also be targeted by LECT2. Here, we sought to determine the role of
LECT2 in tumor angiogenesis in HCC patients. We found that LECT2 expression
inhibited tumor growth via angiogenesis in the HCC xenograft model. Specifically,
we demonstrated that recombinant human LECT2 protein selectively suppressed
vascular endothelial growth factor (VEGF)165-induced endothelial cell
proliferation, migration, and tube formation in vitro and in vivo.
Mechanistically, LECT2 reduced VEGF receptor 2 tyrosine phosphorylation and its
downstream extracellular signal-regulated kinase and AKT phosphorylation.
Furthermore, LECT2 gene expression correlated negatively with angiogenesis in HCC
patients. Taken together, our findings demonstrate that LECT2 inhibits VEGF165
induced HCC angiogenesis through directly binding to VEGFR2 and has broad
applications in treating VEGF-mediated solid tumors.
PMID- 27507764
TI - HPA axis dysregulation, NR3C1 polymorphisms and glucocorticoid receptor isoforms
imbalance in metabolic syndrome.
AB - CONTEXT: Metabolic syndrome (MetS) shares several similarities with
hypercortisolism. OBJECTIVES: To evaluate hypothalamic-pituitary-adrenal (HPA)
axis sensitivity to dexamethasone (DEX), NR3C1 single nucleotide polymorphisms
(SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in
peripheral immune cells of MetS patients and controls. DESIGN: Prospective study
with 40 MetS patients and 40 controls was conducted at the Ribeirao Preto Medical
School University Hospital. METHODS: Plasma and salivary cortisol were measured
in basal conditions and after 0.25, 0.5, and 1 mg of DEX given at 2300 h. In
addition, p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) SNPs
were evaluated by quantitative polymerase chain reaction allelic discrimination.
Exons 3 to 9 and exon/intron boundaries of NR3C1 were sequenced. GR isoforms and
cytokines (IL1B, IL2, IL4, IL6, IL8, IL10, IFNgamma, TNFalpha) expression were
assessed by quantitative polymerase chain reaction. RESULTS: Plasma and salivary
cortisol (nmol/L) after 1-mg DEX were higher in MetS patients compared with
controls (PF: 70.2 +/- 17.3 vs 37.9 +/- 2.6, P = .02, and SF: 4.9 +/- 1.7 vs 2.2
+/- 0.3, P < .0001). After all DEX doses, a lower number of MetS patients
suppressed plasma and salivary cortisol compared with controls. The BclI
genotypic frequencies (%) differed between patients (CC:56/CG:44) and controls
(CC:50/CG:32.5/GG:17.5) (P = .03). The GRbeta was overexpressed (fold = 100.0; P
= .002) and IL4 (fold = -265.0; P < .0001) was underexpressed in MetS.
CONCLUSION: MetS patients exhibited decreased HPA sensitivity to glucocorticoid
feedback. Moreover, the BclI polymorphism lower frequency, GRbeta overexpression,
and IL4 underexpression might underlie the molecular mechanism of glucocorticoid
resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS
pathogenesis.
PMID- 27507765
TI - Comparative transcriptome analysis reveals a global insight into molecular
processes regulating citrate accumulation in sweet orange (Citrus sinensis).
AB - Citrate, the predominant organic acid in citrus, determines the taste of these
fruits. However, little is known about the synergic molecular processes
regulating citrate accumulation. Using 'Dahongtiancheng' (Citrus sinensis) and
'Bingtangcheng' (C. sinensis) with significant difference in citrate, the
objectives of this study were to understand the global mechanisms of high-citrate
accumulation in sweet orange. 'Dahongtiancheng' and 'Bingtangcheng' exhibit
significantly different patterns in citrate accumulation throughout fruit
development, with the largest differences observed at 50-70 days after full bloom
(DAFB). Comparative transcriptome profiling was performed for the endocarps of
both cultivars at 50 and 70 DAFB. Over 34.5 million clean reads per library were
successfully mapped to the reference database and 670-2630 differentially
expressed genes (DEGs) were found in four libraries. Among the genes, five
transcription factors were ascertained to be the candidates regulating citrate
accumulation. Functional assignments of the DEGs indicated that photosynthesis,
the citrate cycle and amino acid metabolism were significantly altered in
'Dahongtiancheng'. Physiological and molecular analyses suggested that high
photosynthetic efficiency and partial impairment of citrate catabolism were
crucial for the high-citrate trait, and amino acid biosynthesis was one of the
important directions for citrate flux. The results reveal a global insight into
the gene expression changes in a high-citrate compared with a low-citrate sweet
orange. High accumulating efficiency and impaired degradation of citrate may be
associated with the high-citrate trait of 'Dahongtiancheng'. Findings in this
study increase understanding of the molecular processes regulating citrate
accumulation in sweet orange.
PMID- 27507766
TI - Melatonin abrogates nonylphenol-induced testicular dysfunction in Wistar rats.
AB - Endocrine-disrupting chemicals present in the environment can bring about
hormonal imbalance and be potentially harmful to the human health. Alkylphenols
are omnipresent in the environment as they are constituents of several products.
The aim of this study was to evaluate the effect of exogenous melatonin treatment
on nonylphenol (NP)-induced oxidative stress and testicular toxicity in Wistar
rats using biochemical and histopathological parameters. The oxidative stress
biomarkers, activities of enzymatic and non-enzymatic antioxidants and
histopathological evaluation were performed in testicular tissues. NP caused
elevated TBARS levels and marked alteration of both nonenzymatic and enzymatic
biomarkers. Furthermore, severe histopathological alterations were observed in
the testis of NP-exposed animals as compared with that of the control rats.
Melatonin supplementation ameliorated the alterations in these biochemical and
histopathological variables in rats. In conclusion, our results demonstrated that
melatonin through its antioxidant activity effectively protected against the NP
induced testicular toxicity.
PMID- 27507767
TI - Childhood-Diagnosed ADHD, Symptom Progression, and Reversal Learning in
Adulthood.
AB - OBJECTIVE: ADHD persists in up to 60% into adulthood, and the reasons for
persistence are not fully understood. The objective of this study was to
characterize the neurofunctional basis of decision making in those with a
childhood diagnosis of ADHD with either persistent or remitted symptoms in
adulthood versus healthy control participants. METHOD: Thirty-two adults
diagnosed with ADHD as children were split into persistent ( n = 18) or remitted
( n = 14) ADHD groups. Their neural activity and neurofunctional connectivity
during a probabilistic reversal learning task were compared with 32 healthy
controls. RESULTS: Remitters showed significantly higher neural connectivity in
final reversal error and probabilistic error conditions, and persisters depict
higher neural connectivity in reversal errors than controls at a family-wise
error (FWE) corrected whole-brain corrected threshold. CONCLUSION: Remitters may
have utilized higher neural connectivity than controls to make successful
decisions. Also, remitters may have utilized compensatory strategies to override
any potential underlying ADHD deficits.
PMID- 27507768
TI - Creating Virtual Integration and Improved Oncology Care Quality Through a Co
Management Services Agreement.
AB - PURPOSE: Implementation of a co-management services agreement (Co-MSA) creates
agreed-upon cancer care delivery quality metrics, a forum for discussion of
service line oversight, and virtually integrated care without institutional
employment of oncologists. The goal of this project was to demonstrate that a Co
MSA improved predefined quality metrics and provided enhanced communications
between a health system's oncology service line and a group of independent
oncologists. METHODS: Iterative planning discussions were scheduled biweekly over
an 18-month period. Contractual, quality, and clinical data with benchmarking
were considered in the creation of the Co-MSA. Review of the first year's
implementation occurred through examination of the metric achievements and
qualitative themes that arose through committee meetings, clinical implementation
processes, and cross-organizational discussions. RESULTS: Metrics designed for
the Co-MSA included improved adherence to the breast cancer, colon cancer, and
non-small-cell lung cancer level I pathways; improvement of the medical oncology
physician communication component of the hospital system's Hospital Consumer
Assessment of Healthcare Providers and Systems survey scores; and increased
delivery of survivorship care plans to appropriate patients. Nonquantifiable
themes from the first year of implementation included the need for technology to
collect data, both organizations needing a wider understanding of quality
improvement techniques, and a need for greater executive leadership involvement.
CONCLUSION: In its first year, the Co-MSA resulted in improvement of the delivery
of survivorship care plans and adherence to value pathways powered by the
National Comprehensive Cancer Network. Improvement of Hospital Consumer
Assessment of Healthcare Providers and Systems scores did not occur.
PMID- 27507769
TI - Population-Based Precision Cancer Screening: A Symposium on Evidence,
Epidemiology, and Next Steps.
AB - Precision medicine, an emerging approach for disease treatment that takes into
account individual variability in genes, environment, and lifestyle, is under
consideration for preventive interventions, including cancer screening. On
September 29, 2015, the National Cancer Institute sponsored a symposium entitled
"Precision Cancer Screening in the General Population: Evidence, Epidemiology,
and Next Steps". The goal was two-fold: to share current information on the
evidence, practices, and challenges surrounding precision screening for breast,
cervical, colorectal, lung, and prostate cancers, and to allow for in-depth
discussion among experts in relevant fields regarding how epidemiology and other
population sciences can be used to generate evidence to inform precision
screening strategies. Attendees concluded that the strength of evidence for
efficacy and effectiveness of precision strategies varies by cancer site, that no
one research strategy or methodology would be able or appropriate to address the
many knowledge gaps in precision screening, and that issues surrounding
implementation must be researched as well. Additional discussion needs to occur
to identify the high priority research areas in precision cancer screening for
pertinent organs and to gather the necessary evidence to determine whether
further implementation of precision cancer screening strategies in the general
population would be feasible and beneficial. Cancer Epidemiol Biomarkers Prev;
25(11); 1449-55. (c)2016 AACR.
PMID- 27507770
TI - Use of Electronic Health Data to Estimate Heart Failure Events in a Population
Based Cohort with CKD.
AB - BACKGROUND AND OBJECTIVES: Studies that use electronic health data typically
identify heart failure (HF) events from hospitalizations with a principal
diagnosis of HF. This approach may underestimate the total burden of HF among
persons with CKD. We assessed the accuracy of algorithms for identifying
validated HF events from hospitalizations and outpatient encounters, and we used
this validation information to estimate the rate of HF events in a large CKD
population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified a cohort
of 15,141 adults age 18-89 years with an eGFR<60 ml/min per 1.73 m2 from 2008 to
2011. Potential HF events during follow-up were randomly sampled for validation
with medical record review. Positive predictive values from the validation study
were used to estimate the rate of validated HF events in the full cohort.
RESULTS: A total of 1864 participants had at least one health care encounter that
qualified as a potential HF event during 2.7 years of mean follow-up. Among 313
potential events that were randomly sampled for validation, positive predictive
values were 92% for hospitalizations with a principal diagnosis of HF, 32% for
hospitalizations with a secondary diagnosis of HF, and 70% for qualifying
outpatient HF encounters. Through use of this validation information in the full
cohort, the rate of validated HF events estimated from the most comprehensive
algorithm that included principal and secondary diagnosis hospitalizations and
outpatient encounters was 35.2 events/1000 person-years (95% confidence interval,
33.1 to 37.4), compared with 9.5 events/1000 person-years (95% confidence
interval, 8.7 to 10.5) from the algorithm that included only principal diagnosis
hospitalizations. Outpatient encounters accounted for 20% of the total number of
validated HF events. CONCLUSIONS: In studies that rely on electronic health data,
algorithms that include hospitalizations with a secondary diagnosis of HF and
outpatient HF encounters more fully capture the burden of HF, although validation
of HF events may be necessary with this approach.
PMID- 27507771
TI - A simple scoring system to assess the need for an endoscopic intervention in
suspected upper gastrointestinal bleeding: A prospective cohort study.
AB - BACKGROUND: Assessment of the emergent endoscopy for upper gastrointestinal
bleeding (UGIB) patients has important clinical implications. There is no
validated criterion to triage. AIMS: To develop a simple score predicting an
endoscopic intervention. METHODS: A prospective cohort study was conducted at a
tertiary care centre. Primary outcome was the high-risk stigmata which were well
established endoscopic findings to determine the need for an endoscopic
intervention. We created a simple score by multivariable logistic regression and
compared with the Glasgow Blatchford Score (GBS). External validation was
performed in a second cohort. RESULTS: 284 of consecutive 568 patients with
suspected UGIB had the high-risk stigmata. Three variables were selected: "no
daily use of proton pump inhibitors during one week before examination (+1
point)", "shock index (heart rate/systolic blood pressure)>=1 (+1 point)" and
"urea/creatinine>=140 (blood urea nitrogen/creatinine>=30) (+1 point)". The
accumulating score (range 0-3) achieved an area under the receiver-operating
characteristic curve (AUC) of 0.74 (95% confidence interval [CI], 0.70-0.78),
which was superior to the GBS (AUC, 0.63; 95% CI, 0.59-0.68; p<0.001). Validation
in an external cohort demonstrated superiority to the GBS (AUC, 0.78 vs. 0.59;
p<0.001). CONCLUSIONS: The simple score has greater accuracy than the GBS for
assessing the need for an endoscopic intervention in cases of suspected UGIB.
Further external validation should be performed to verify generalizability.
PMID- 27507772
TI - Localization of glutamatergic, GABAergic, and cholinergic neurons in the brain of
the African cichlid fish, Astatotilapia burtoni.
AB - Neural communication depends on release and reception of different
neurotransmitters within complex circuits that ultimately mediate basic
biological functions. We mapped the distribution of glutamatergic, GABAergic, and
cholinergic neurons in the brain of the African cichlid fish Astatotilapia
burtoni using in situ hybridization to label vesicular glutamate transporters
(vglut1, vglut2.1, vglut3), glutamate decarboxylases (gad1, gad2), and choline
acetyltransferase (chat). Cells expressing the glutamatergic markers vgluts 1-3
show primarily nonoverlapping distribution patterns, with the most widespread
expression observed for vglut2.1, and more restricted expression of vglut1 and
vglut3. vglut1 is prominent in granular layers of the cerebellum, habenula,
preglomerular nuclei, and several other diencephalic, mesencephalic, and
rhombencephalic regions. vglut2.1 is widely expressed in many nuclei from the
olfactory bulbs to the hindbrain, while vglut3 is restricted to the hypothalamus
and hindbrain. GABAergic cells show largely overlapping gad1 and gad2 expression
in most brain regions. GABAergic expression dominates nuclei of the subpallial
ventral telencephalon, while glutamatergic expression dominates nuclei of the
pallial dorsal telencephalon. chat-expressing cells are prominent in motor
cranial nerve nuclei, and some scattered cells lie in the preoptic area and
ventral part of the ventral telencephalon. A localization summary of these
markers within regions of the conserved social decision-making network reveals a
predominance of either GABAergic or glutamatergic cells within individual nuclei.
The neurotransmitter distributions described here in the brain of a single fish
species provide an important resource for identification of brain nuclei in other
fishes, as well as future comparative studies on circuit organization and
function. J. Comp. Neurol. 525:610-638, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27507773
TI - Application of compound mixture of caprylic acid, iron and mannan oligosaccharide
against Sparicotyle chrysophrii (Monogenea: Polyopisthocotylea) in gilthead sea
bream, Sparus aurata.
AB - We have evaluated the therapeutic effect of a compound mixture of caprylic acid
(200 mg/kg fish), organic iron (0.2% of diet) and mannan oligosaccharide (0.4% of
diet) in gilthead sea bream, Sparus aurata Linnaeus, infected with Sparicotyle
chrysophrii Beneden et Hesse, 1863 in controlled conditions. One hundred and ten
reared and S. chrysophrii-free fish (197 g) located in a cement tank were
infected by the parasite two weeks following the addition of 150 S. chrysophrii
infected fish (70 g). Growth parameters and gill parasitic load were measured in
treated against control fish after a ten-week-period. Differences in final
weight, feed conversion ratio, specific growth rate and feed efficiency were not
statistically significant between the experimental groups, suggesting no evident
effect with respect to fish growth during the study period. Although the
prevalence of S. chrysophrii was not affected by the mixture at the end of the
experiment, the number of adults and larvae was significantly lower. The mean
intensity encompassing the number of adults and larvae was 8.1 in treated vs 17.7
in control fish. Individual comparisons of gill arches showed that the preferred
parasitism site for S. chrysophrii it the outermost or fourth gill arch,
consistently apparent in fish fed the modified diet and in control fish. In
conclusion, the combined application of caprylic acid, organic iron and mannan
oligosaccharide can significantly affect the evolution of infection with S.
chrysophrii in gilthead sea bream, being capable of reducing adult and larval
stages of the monogenean. However, no difference in growth improvement was
observed after the trial period, potentially leaving space for further
optimisation of the added dietary compounds.
PMID- 27507774
TI - The costs and benefits of brain dopamine for cognitive control.
AB - Cognitive control helps us attain our goals by resisting distraction and
temptations. Dopaminergic drugs are well known to enhance cognitive control.
However, there is great variability in the effects of dopaminergic drugs across
different contexts, with beneficial effects on some tasks but detrimental effects
on other tasks. The mechanisms underlying this variability across cognitive task
demands remain unclear. I aim to elucidate this across-task variability in
dopaminergic drug efficacy by going beyond classic models that emphasize the
importance of dopamine in the prefrontal cortex for cognitive control and working
memory. To this end, I build on recent advances in cognitive neuroscience that
highlight a role for dopamine in cost-benefit decision making. Specifically, I
reconceptualize cognitive control as involving not just prefrontal dopamine but
also modulation of cost-benefit decision making by striatal dopamine. This
approach will help us understand why we sometimes fail to (choose to) exert
cognitive control while also identifying mechanistic factors that predict
dopaminergic drug effects on cognitive control. WIREs Cogn Sci 2016, 7:317-329.
doi: 10.1002/wcs.1401 For further resources related to this article, please visit
the WIREs website.
PMID- 27507775
TI - The Clinical Significance of N-terminal Pro-brain Natriuretic Peptide in
Detecting the Residual Cardiovascular Risk in Hypertension and Other Clinical
Conditions and in Predicting Future Cardiovascular Events.
PMID- 27507777
TI - Ternary dendritic nanowires as highly active and stable multifunctional
electrocatalysts.
AB - Multimetallic nanocatalysts with a controlled structure can provide enhanced
catalytic activity and durability by exploiting electronic, geometric, and strain
effects. Herein, we report the synthesis of a novel ternary nanocatalyst based on
Mo doped PtNi dendritic nanowires (Mo-PtNi DNW) and its bifunctional application
in the methanol oxidation reaction (MOR) at the anode and the oxygen reduction
reaction (ORR) at the cathode for direct methanol fuel cells. An unprecedented Mo
PtNi DNW structure can combine multiple structural attributes of the 1D nanowire
morphology and dendritic surfaces. In the MOR, Mo-PtNi DNW exhibits superior
activity to Pt/C and Mo doped Pt dendritic nanowires (Mo-Pt DNW), and excellent
durability. Furthermore, Mo-PtNi DNW demonstrates excellent activity and
durability for the ORR. This work highlights the important role of compositional
and structural control in nanocatalysts for boosting catalytic performances.
PMID- 27507776
TI - Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium
Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions.
AB - The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS)
has no specific conventional MRI correlates. Clinicians therefore stipulate
improved imaging specificity to define the pathological substrates of MS in vivo
including mapping of intracellular sodium accumulation. Based upon preclinical
findings and results of previous sodium MRI studies in MS patients we
hypothesized that the fluid-attenuated sodium signal differs between acute and
chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS
patients; lesion type was defined by the presence or absence of contrast
enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed
models were applied to predict lesion type based on sodium signals; thereby
controlling for varying numbers of lesions among patients and confounding
variables such as age and medication. Hierarchical model comparisons revealed
that both sodium signals average tissue (chi(2)(1) = 27.89, p < 0.001) and fluid
attenuated (chi(2)(1) = 5.76, p = 0.016) improved lesion type classification.
Sodium MRI signals were significantly elevated in acute compared to chronic
lesions compatible with intracellular sodium accumulation in acute MS lesions. If
confirmed in further studies, sodium MRI could serve as biomarker for diagnostic
assessment of MS, and as readout parameter in clinical trials promoting
attenuation of chronic inflammation.
PMID- 27507778
TI - Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol and Lipid
Peroxidation in the Rat Plasma.
AB - Sleep deprivation (SD) is biological stressor that alters metabolic parameters,
induced oxidative stress and lipid peroxidation. Previous studies have shown that
antioxidants substances such as melatonin, tryptophan, vitamin E and vitamin C
improved stress tolerance in laboratory animals. In this study, we examined the
potential protective effects of administration of vitamin C on acute and chronic
sleep deprivation-induced metabolic derangement. In addition, possible processes
involved in vitamin C effects on acute and chronic sleep deprivation-induced
metabolic derangement were determined. Thirty-five rats (120-250g) were used. The
rats were divided into 7 groups of 5 rats each as Control (CTRL), Acute sleep
deprived untreated with vitamin C (AC), Acute sleep deprived treated with vitamin
C (AWC), Chronic sleep deprived untreated with vitamin C (CC), Chronic sleep
deprived treated with vitamin C (CWC), Chronic sleep deprived + Recovery
untreated with vitamin C (RC), and Chronic sleep deprived + Recovery treated with
vitamin C (RWC). The SD was carried out for 20h for 1 day on the acute groups,
and for 20h/day for 5 days on the chronic group, using the Multiple Modified
Platforms (MMP) after oral administration of 300mg/kg of vitamin C to all vitamin
C-treated groups. The recovery groups were further observed for five days after
SD. The control group were treated with vitamin C and without stress in their
home cages. At the end of the experiment, the animals were sacrificed and blood
was collected for estimation of plasma glucose, insulin, cortisol and
malondialdehyde (MDA). The results showed that acute and chronic SDs
significantly increased MDA and cortisol levels, while significantly reduced the
levels of insulin. Treatment with vitamin C reversed the changes in the MDA,
cortisol and plasma insulin levels. Additionally, allowing the rats to recover
for 5 days after sleep deprivation corrected the observed changes. Plasma glucose
was significantly reduced in all the sleep deprived groups compared to the
control. In conclusion, sleep deprivation induced metabolic, hormonal and lipid
peroxidation derangement, and treatment with vitamin C prevented these
impairments. Thus, the effects of vitamin C could improve stress tolerance in
rats.
PMID- 27507779
TI - Honey Attenuates the Detrimental Effects of Nicotine on Testicular Functions in
Nicotine Treated Wistar Rats.
AB - Effect of honey on reproductive functions of male rats exposed to nicotine was
examined in this study. Thirty-two adult male wistar rats (n=8/Group) were
grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg
bwt) and Nicotine with Honey. The animals were orally treated for 35 days
consecutively. Epididymis sperm motility, viability, morphology and counts were
estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and
Testosterone were assayed using ELISA method and testicular histology were also
assessed. Significant reduction in percentage sperm motility, viability,
morphology and counts were observed in nicotine group compared to control. Serum
FSH, LH and testosterone levels were significantly reduced in nicotine group when
compared with the control. There was significant improvement in sperm motility,
viability, morphology, counts, FSH, LH and Testosterone in group co-treated with
nicotine and honey relative to nicotine group. Also, the degenerative
seminiferous tubule architecture due to nicotine was improved by honey. In
conclusion, honey may suppress nicotine toxic effect on reproductive functions in
male Wistar rats.
PMID- 27507780
TI - Healing Potentials of Oral Moringa Oleifera Leaves Extract and Tetracycline on
Methicillin Resistant Staphylococcus Aureus Infected Wounds of Wistar rats.
AB - The effects of oral dose of aqueous extract of Moringa oleifera and tetracycline
antibiotics on cutaneous wounds infected with Staphylococcus aureus were studied
in eighteen adult wistar rats (159+/-31.5g) randomized into three groups: Group
A, n = 6, Moringa oleifera-(300 mg/kg). Group B, n = 6, tetracycline (9.4 mg/kg)
and Group C, n = 6, Sterile water (control). Six millimetres diameter nape wound,
created on each rat under 2% xylazine (5 mg/kg) and 5% ketamine (35 mg/kg), was
contaminated with Staphylococcus aureus (108 Colony Forming Unit (CFU). Following
infection, treatment was commenced with daily oral dose of test preparations and
the wounds were evaluated every other day i.e., day 3, 5, 7, 9, 11, 13 and 15 for
wetness (wound exudation), wound edge oedema, hyperaemia, granulation tissues and
contraction (diameter). Severe wound exudation existed in all the groups between
days 0-3 (p = 1.00). A significantly less wound exudation was observed at days 3
5 (p = 0.000) and 5-9 (p = 0.003) (Control< Tetracycline Moringa> Tetracycline). Differences in wound diameter was
not significant except at days 5-9 (p = 0.013) (Control> Moringa >Tetracycline).
Oral doses of Moringa oleifera extract (300mg/kg) and tetracycline (9.4mg/kg) are
not effective as antimicrobial or immune-boosting agents to enhance healing of
wounds infected with Staphylococcus aureus and hence not recommended for rapid
clearance of Staphylococcus aureus infected wounds.
PMID- 27507781
TI - Genistein Precipitated Hypothyroidism, Altered Leptin and C-Reactive Protein
Synthesis in Pregnant Rats.
AB - Genistein is an isoflavone constituent of soya. This study examined the mechanism
by which genistein produced adverse effects in pregnant laboratory rats. Pregnant
rats were divided into control (Con) and genistein (Gen) force fed (2 mg/kg)
groups. At terminal gestation day (GD) ranging from 0-20, the rats were
sacrificed, and blood samples and amniotic fluids were collected. Thyroid
hormone, C-reactive protein (CRP) and leptin assay was carried using the blood
samples. Leptin was also assayed in the placenta and amniotic fluid supernatant.
Oral exposure of pregnant rats to genistein significantly altered maternal T3,
(GD18; Con 1.65 +/- 0.01, Gen 1.03 +/- 0.04 nmol/L), T4 (GD6; Con 29.60 +/- 0.00,
Gen 36.04 +/- 1.29 nmol/L), Leptin (Placenta GD20; Con 0.08 +/- 0.01, Gen 0.31 +/
0.02 ng/ml, amniotic fluid ;GD 20; Con 0.02 +/- 0.00, Gen 0.35 +/- 0.05 ng/ml)
in genistein group. These changes were accompanied with loss of embryonic
implants and a decrease in fetal and placental weights. The CRP level was
significantly decreased and increased at the onset and toward late pregnancy
respectively. Oral exposure of pregnant rats to genistein precipitated
hypothyroidism, altered some metabolic hormones with a reduction in fetal and
placental growth and increased resorption of embryonic implants.
PMID- 27507782
TI - Effect of Ethanolic Leaf Extract of Senna Fistula on some Haematological
Parameters, Lipid Profile and Oxidative Stress in Alloxan-induced Diabetic Rats.
AB - Increasing evidence in both experimental and clinical studies suggests that
oxidative stress plays a major role in the pathogenesis of both types of diabetes
mellitus. The disease is also known to adversely affect some haematological
parameters and cause dyslipidemia. This study was designed to investigate the
effect of chronic administration of ethanolic leave extract of Senna fistula on
haematological values, oxidative stress and dyslipidemia in experimental diabetic
rats. Twenty-four albino rats weighing 120-150 g were divided into 4 experimental
groups of six rats each; control, diabetic untreated, diabetic treated with
glibenclamide and diabetic treated with 100 mg/kg b.w of Senna fistula. Diabetes
was induced by 100 mg/kg b.w. of alloxan monohydrates. The control and diabetic
groups received normal saline while the diabetic treated groups were administered
with 5mg/kg and 100mg/kg body weight of glibenclamide and ethanolic leaves
extract of Senna fistula respectively for 28 days. At the end of experimental
period blood samples were taken from the animals for the determination of Red
blood cells (RBC), packed cell volume (PCV), Haemoglobin concentration (Hb),
total cholesterol, triglycerides (TG), high density lipoprotein (HDL), low
density lipoprotein (LDL) and malondialdehyde (MDA), marker of lipid
peroxidation. The result showed that in diabetic rats, PCV, RBC and Hb were
decreased but the application of the extract increased the parameters. Similarly,
the result showed a significant increase in total cholesterol, TG and LDL level
of the diabetic group when compared with the control, glibenclamide and extract
treated diabetic groups, however, there was no significant difference in HDL
level in all the groups. The result also showed a significant decrease in
elevated MDA of diabetic treated rats. These findings suggest that ethanolic
leaves extract of Senna fistula might improve the diabetic induced disturbances
of some haematological parameters, reduces the plasma lipid imbalances and
decreases the production of free radicals associated with diabetes.
PMID- 27507783
TI - An evidence-based system for health surveillance of occupational divers.
AB - BACKGROUND: The value of the commonly required routine annual medical examination
of occupational divers has been questioned, and there is a need for a robust,
evidence-based system of health surveillance for this group of workers. AIMS: To
determine whether the medical examination and investigation component of
occupational divers' routine comprehensive health surveillance adds significantly
to the information gained from the questionnaire component in determining fitness
for diving. METHODS: An occupational diver database was interrogated to identify
divers issued with a 'limited' medical clearance or considered 'unfit' for diving
over a 5-year period. Reasons for the 'unfit' or 'limited' designation and the
source of the critical information, whether the annual health questionnaire or
the medical examination or questionnaire component (or both) of the initial or 5
yearly comprehensive medical evaluation, was recorded. For divers completing the
5-yearly repeat comprehensive medical evaluation, the sensitivity and specificity
of the questionnaire alone for determining unfitness for diving was compared with
that of a nominal 'gold standard'. RESULTS: Of 5178 certificates issued to 2187
divers over a 5-year period, 158 (3%) were provisionally designated as either
'limited' or 'unfit'. Of nine divers identified by the examination component of
the 5-yearly comprehensive medical evaluation, four were eventually designated
'fit', two 'limited', and three were lost to follow up. None who had completed
subsequent investigations remained 'unfit'. The sensitivity and specificity of
the questionnaire to detect unfit divers compared with the gold standard were
84.6 and 99.3%, respectively, and its accuracy was 98.9%. CONCLUSION: The current
New Zealand occupational diver medical certification process, comprising annual
health questionnaires and 5-yearly full examinations, detects all health issues
critical to the determination of fitness to dive.
PMID- 27507784
TI - Activation of p38 Mitogen-Activated Protein Kinase by Clotrimazole Induces
Multidrug Resistance-Associated Protein 3 Activation through a Novel
Transcriptional Element.
AB - Multidrug resistance-associated protein 3 (MRP3) is a basolaterally localized
transporter in the liver and contributes to the transport of various metabolites
such as conjugates of endogenous compounds and drugs from hepatocytes. MRP3
expression in the human liver is low under normal physiologic conditions but is
induced by drug treatment. Although several studies have identified a region
necessary for the basal transcription of MRP3, no region that responds to drugs
has been reported. To identify the xenobiotic-responsive elements of MRP3, we
constructed a luciferase reporter plasmid containing the MRP3 5'-flanking region
up to -10 kb upstream from the transcription start site. Among typical nuclear
receptor ligands, clotrimazole dramatically enhanced MRP3 reporter activity in
HepG2 cells, whereas rifampicin had no effect. We then conducted MRP3 reporter
assays with deletion or mutation constructs to identify a clotrimazole-responsive
element. The element was located approximately -6.8 kb upstream from the MRP3
transcription start site. Overexpression of the pregnane X receptor did not
enhance clotrimazole-mediated transcription. We found that clotrimazole was toxic
to HepG2 cells and we therefore investigated whether mitogen-activated protein
kinase (MAPK) activation is involved in the transactivation of MRP3 by
clotrimazole. p38 MAPK inhibitor SB203580 [4-(4-fluorophenyl)-2-(4
methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole] suppressed MRP3 mRNA expression
induced by clotrimazole, whereas c-Jun N-terminal kinase inhibitor SP600125 (1,9
pyrazoloanthrone) and extracellular signal-regulated kinase inhibitor PD98059 [2
(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one] did not. Phosphorylated p38 MAPK
was detected in HepG2 cells treated with clotrimazole. These results suggest that
activation of the p38 MAPK pathway induces the transcriptional activation of
MRP3.
PMID- 27507785
TI - Intercellular ultrafast Ca(2+) wave in vascular smooth muscle cells: numerical
and experimental study.
AB - Vascular smooth muscle cells exhibit intercellular Ca(2+) waves in response to
local mechanical or KCl stimulation. Recently, a new type of intercellular Ca(2+)
wave was observed in vitro in a linear arrangement of smooth muscle cells. The
intercellular wave was denominated ultrafast Ca(2+) wave and it was suggested to
be the result of the interplay between membrane potential and Ca(2+) dynamics
which depended on influx of extracellular Ca(2+), cell membrane depolarization
and its intercel- lular propagation. In the present study we measured
experimentally the conduction velocity of the membrane depolarization and
performed simulations of the ultrafast Ca(2+) wave along coupled smooth muscle
cells. Numerical results reproduced a wide spectrum of experimental observations,
including Ca(2+) wave velocity, electrotonic membrane depolarization along the
network, effects of inhibitors and independence of the Ca(2+) wave speed on the
intracellular stores. The numerical data also provided new physiological insights
suggesting ranges of crucial model parameters that may be altered experimentally
and that could significantly affect wave kinetics allowing the modulation of the
wave characteristics experimentally. Numerical and experimental results supported
the hypothesis that the propagation of membrane depolarization acts as an
intercellular messenger mediating intercellular ultrafast Ca(2+) waves in smooth
muscle cells.
PMID- 27507787
TI - Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe
for Single-Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous
Chondrons.
AB - Traditionally, mesenchymal stem cells (MSCs) isolated from adult bone marrow were
described as being capable of differentiating to various lineages including
cartilage. Despite increasing interest in these MSCs, concerns regarding their
safety, in vivo behavior and clinical effectiveness have restrained their
clinical application. We hypothesized that MSCs have trophic effects that
stimulate recycled chondrons (chondrocytes with their native pericellular matrix)
to regenerate cartilage. Searching for a proof of principle, this phase I (first
in-man) clinical trial applied allogeneic MSCs mixed with either 10% or 20%
recycled autologous cartilage-derived cells (chondrons) for treatment of
cartilage defects in the knee in symptomatic cartilage defect patients. This
unique first in man series demonstrated no treatment-related adverse events up to
one year postoperatively. At 12 months, all patients showed statistically
significant improvement in clinical outcome compared to baseline. Magnetic
resonance imaging and second-look arthroscopies showed completely filled defects
with regenerative cartilage tissue. Histological analysis on biopsies of the
grafts indicated hyaline-like regeneration with a high concentration of
proteoglycans and type II collagen. Short tandem repeat analysis showed the
regenerative tissue only contained patient-own DNA. These findings support the
novel insight that the use of allogeneic MSCs is safe and opens opportunities for
other applications. Stem cell-induced paracrine mechanisms may play an important
role in the chondrogenesis and successful tissue regeneration found. Stem Cells
2017;35:256-264.
PMID- 27507788
TI - Psychometric Analysis of the Multidimensional State Boredom Scale and Its
Condensed Versions.
AB - The Multidimensional State Boredom Scale (MSBS) is a promising new self-report
measure of state boredom. Two condensed versions of the scale have also been
introduced. This study helped explore the psychometric qualities of these scales,
using a large sample of Australian adults ( N = 1,716), as well as two smaller
samples ( N = 199 and N = 422). Data analyses indicated strong convergent
validity and very high internal consistency for the scales. Test-retest
reliability over a 6- to 8-day period was moderately high. Confirmatory factor
analyses of the MSBS authors' suggested factor structure indicated good fit for
this model. However, some of the data analyses raise questions as to whether the
scale includes meaningful subfactors. Overall, the MSBS (and Short Form) is
recommended for researchers who wish to assess state boredom.
PMID- 27507786
TI - Assessing the Cognitive Translational Potential of a Mouse Model of the 22q11.2
Microdeletion Syndrome.
AB - A chromosomal microdeletion at the 22q11.2 locus is associated with extensive
cognitive impairments, schizophrenia and other psychopathology in humans.
Previous reports indicate that mouse models of the 22q11.2 microdeletion syndrome
(22q11.2DS) may model the genetic basis of cognitive deficits relevant for
neuropsychiatric disorders such as schizophrenia. To assess the models usefulness
for drug discovery, a novel mouse (Df(h22q11)/+) was assessed in an extensive
battery of cognitive assays by partners within the NEWMEDS collaboration
(Innovative Medicines Initiative Grant Agreement No. 115008). This battery
included classic and touchscreen-based paradigms with recognized sensitivity and
multiple attempts at reproducing previously published findings in 22q11.2DS mouse
models. This work represents one of the most comprehensive reports of cognitive
functioning in a transgenic animal model. In accordance with previous reports,
there were non-significant trends or marginal impairment in some tasks. However,
the Df(h22q11)/+ mouse did not show comprehensive deficits; no robust impairment
was observed following more than 17 experiments and 14 behavioral paradigms. Thus
- within the current protocols - the 22q11.2DS mouse model fails to mimic the
cognitive alterations observed in human 22q11.2 deletion carriers. We suggest
that the 22q11.2DS model may induce liability for cognitive dysfunction with
additional "hits" being required for phenotypic expression.
PMID- 27507789
TI - Assessing Context-Specific Attributions During Couples' Conflict Interactions.
AB - Two studies were conducted to develop and validate a six-item scale for measuring
context-specific attributions regarding the extent to which people either blame
or exonerate partners during couples' conflicts. Context-specific attributions
pertain to appraisals made during a single episode of relationship conflict, and
the scale was expected to be distinct from existing attribution scales measuring
people's schemas regarding the types of attributions they typically make. Study 1
included 2,452 people in marriage or cohabitating relationships; Study 2 included
172 people in dating relationships, and participants in both studies completed
Internet questionnaires. Item response theory was used to create an attribution
scale using the fewest number of items to discriminate reliably across the full
range of attribution levels. The resulting scale produced an expected pattern of
convergent and divergent correlations with other context-specific measures,
including two types of underlying concerns and three types of emotion. The
context-specific attribution scale explained variance in these criterion
variables that could not be explained by other existing scales that assess
attributions at the schematic level.
PMID- 27507790
TI - Proactive therapeutic drug monitoring of infliximab: a comparative study of a new
point-of-care quantitative test with two established ELISA assays.
AB - BACKGROUND: Therapeutic drug monitoring is a powerful strategy known to improve
the clinical outcomes and to optimise the healthcare resources in the treatment
of autoimmune diseases. Currently, most of the methods commercially available for
the quantification of infliximab (IFX) are ELISA-based, with a turnaround time of
approximately 8 h, and delaying the target dosage adjustment to the following
infusion. AIM: To validate the first point-of-care IFX quantification device
available in the market - the Quantum Blue Infliximab assay (Buhlmann,
Schonenbuch, Switzerland) - by comparing it with two well-established methods.
METHODS: The three methods were used to assay the IFX concentration of spiked
samples and of the serum of 299 inflammatory bowel diseases (IBD) patients
undergoing IFX therapy. RESULTS: The point-of-care assay had an average IFX
recovery of 92%, being the most precise among the tested methods. The Intraclass
Correlation Coefficients of the point-of-care IFX assay vs. the two ELISA-based
established methods were 0.889 and 0.939. Moreover, the accuracy of the point-of
care IFX compared with each of the two reference methods was 77% and 83%, and the
kappa statistics revealed a substantial agreement (0.648 and 0.738). CONCLUSIONS:
The Quantum Blue IFX assay can successfully replace the commonly used ELISA-based
IFX quantification kits. This point-of-care IFX assay is able to deliver the
results within 15 min makes it ideal for an immediate target concentration
adjusted dosing. Moreover, it is a user-friendly desktop device that does not
require specific laboratory facilities or highly specialised personnel.
PMID- 27507792
TI - Efficient CRISPR-Mediated Post-Transcriptional Gene Silencing in a
Hyperthermophilic Archaeon Using Multiplexed crRNA Expression.
AB - CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-mediated RNA
degradation is catalyzed by a type III system in the hyperthermophilic archaeon
Sulfolobus solfataricus Earlier work demonstrated that the system can be
engineered to target specifically mRNA of an endogenous host reporter gene,
namely the beta-galactosidase in S. solfataricus Here, we investigated the effect
of single and multiple spacers targeting the mRNA of a second reporter gene,
alpha-amylase, at the same, and at different, locations respectively, using a
minimal CRISPR (miniCR) locus supplied on a viral shuttle vector. The use of
increasing numbers of spacers reduced mRNA levels at progressively higher levels,
with three crRNAs (CRISPR RNAs) leading to ~ 70-80% reduction, and five spacers
resulting in an alpha-amylase gene knockdown of > 90% measured on both mRNA and
protein activity levels. Our results indicate that this technology can be used to
increase or modulate gene knockdown for efficient post-transcriptional gene
silencing in hyperthermophilic archaea, and potentially also in other organisms.
PMID- 27507791
TI - Glucose or Altered Ceramide Biosynthesis Mediate Oxygen Deprivation Sensitivity
Through Novel Pathways Revealed by Transcriptome Analysis in Caenorhabditis
elegans.
AB - Individuals with type 2 diabetes display metabolic abnormalities, such as
hyperglycemia, increased free fatty acids, insulin resistance, and altered
ceramide levels, that contribute to vascular dysfunctions and compromised oxygen
delivery. Caenorhabditis elegans fed a glucose-supplemented diet or with altered
ceramide metabolism, due to a hyl-2 mutation, are sensitive to oxygen deprivation
(anoxia). Our experiments showed that the combination of these factors further
decreased the anoxia survival. RNA-sequencing analysis was performed to assess
how a glucose-supplemented diet and/or a hyl-2 mutation altered the
transcriptome. Comparison analysis of transcripts associated with anoxia
sensitive animals [hyl-2(tm2031) mutation or a glucose diet] revealed 199 common
transcripts encoded by genes with known or predicted functions involving innate
immunity, cuticle function (collagens), or xenobiotic and endobiotic phase I and
II detoxification system. Use of RNA interference (RNAi) to target gene products
of the xenobiotic and endobiotic phase I and II detoxification system (UDP
glycosyltransferase and Cytochrome p450 genes; ugt-15, ugt-18, ugt-19, ugt-41,
ugt-63, cyp-13A12, cyp-25A1, and cyp-33C8) increased anoxia survival in wild-type
animals fed a standard diet. Anoxia sensitivity of the hyl-2(tm2031) animals was
suppressed by RNAi of cyp-25A1 or cyp-33C8 genes. A glucose diet fed to the P0
hermaphrodite decreased the anoxia survival of its F1 embryos; however, the RNAi
of ugt-63 and cyp-33C8 suppressed anoxia sensitivity. These studies provide
evidence that the detoxification system impacts oxygen deprivation responses and
that C. elegans can be used to model the conserved detoxification system.
PMID- 27507793
TI - Response of the Pacific inter-tropical convergence zone to global cooling and
initiation of Antarctic glaciation across the Eocene Oligocene Transition.
AB - Approximately 34 million years ago across the Eocene-Oligocene transition (EOT),
Earth's climate tipped from a largely unglaciated state into one that sustained
large ice sheets on Antarctica. Antarctic glaciation is attributed to a threshold
response to slow decline in atmospheric CO2 but our understanding of the feedback
processes triggered and of climate change on the other contents is limited. Here
we present new geochemical records of terrigenous dust accumulating on the sea
floor across the EOT from a site in the central equatorial Pacific. We report a
change in dust chemistry from an Asian affinity to a Central-South American
provenance that occurs geologically synchronously with the initiation of stepwise
global cooling, glaciation of Antarctica and aridification on the northern
continents. We infer that the inter-tropical convergence zone of intense
precipitation extended to our site during late Eocene, at least four degrees
latitude further south than today, but that it migrated northwards in step with
global cooling and initiation of Antarctic glaciation. Our findings point to an
atmospheric teleconnection between extratropical cooling and rainfall climate in
the tropics and the mid-latitude belt of the westerlies operating across the most
pivotal transition in climate state of the Cenozoic Era.
PMID- 27507794
TI - Efficacy of a footbath for post-partum fatigue in South Korea: A quasi
experimental study.
AB - AIM: The purpose of this study was to identify the effects of a footbath on post
partum fatigue. METHODS: This study used a quasi-experimental design by using an
unequivalent control group, pre-post-test design. The participants were divided
into experimental and control groups. Fifty post-partum women who were admitted
to an obstetrics and gynecology ward of a general hospital were the experimental
group and 50 post-partum women who were admitted to an obstetrics and gynecology
ward of a women's hospital were the control group. Two hospitals were providing
similar postnatal care to their patients and they were located in the same city.
The experimental group received a footbath along with postnatal care at the
hospital, while the control group received only postnatal care from the hospital.
Each group completed the Fatigue Continuum Form at a specified time. RESULTS: The
general characteristics and pretest dependent variables were homogenous between
the two groups. The hypothesis was supported post-test as the Fatigue Continuum
Form scores differed significantly between the experimental and the control
groups. CONCLUSION: This study showed that a footbath helps to decrease fatigue
among post-partum women. In addition, it is a good preventative strategy for post
partum women who should initiate it in the early post-partum period.
PMID- 27507795
TI - A Case Indistinguishable Between Indeterminate Cell Histiocytosis and Cutaneous
Rosai-Dorfman Disease.
PMID- 27507796
TI - Prognostic significance of lymph node yield in ypN0 rectal cancer.
AB - BACKGROUND: Neoadjuvant radiation therapy for locally advanced rectal
adenocarcinoma decreases lymph node yield. This study investigated the
association between survival and number of lymph nodes evaluated in patients with
pathologically negative nodes after neoadjuvant therapy. METHODS: Patients with
locally advanced rectal adenocarcinoma who underwent neoadjuvant therapy and had
pathologically negative lymph nodes were included from the Surveillance,
Epidemiology, and End Results (SEER) database over a 7-year interval (January
2004 to December 2010). Systematic dichotomization for optimal cut-off point
identification was performed using statistical modelling. RESULTS: A total of
3995 patients met the inclusion criteria. The majority had T3 (66.7 per cent) and
moderately differentiated (71.5 per cent) tumours. The median number of lymph
nodes retrieved was 12 (i.q.r. 7-16). An optimal cut-off of nine lymph nodes was
identified. Increasing age (P < 0.001), increasing T category (T4 versus T1, P <
0.001; T3 versus T1, P = 0.010), response to neoadjuvant therapy (P < 0.001) and
number of nodes evaluated (P < 0.001) were significant factors for overall
survival in univariable analysis. After adjustment in the multivariable model,
the group with nine or more nodes examined had significantly better overall
survival (hazard ratio (HR) 0.76, 95 per cent c.i. 0.65 to 0.88, P < 0.001; 5
year survival 83.2 versus 78.0 per cent) and cancer-specific survival (HR 0.76,
0.64 to 0.92, P = 0.004; 5-year survival 87.9 versus 85.1 per cent) than the
group with one to eight nodes examined. CONCLUSION: Overall and cancer-specific
survival were worse where fewer than nine lymph nodes were identified after
neoadjuvant therapy for locally advanced rectal cancer.
PMID- 27507797
TI - Terpene metabolic engineering via nuclear or chloroplast genomes profoundly and
globally impacts off-target pathways through metabolite signalling.
AB - The impact of metabolic engineering on nontarget pathways and outcomes of
metabolic engineering from different genomes are poorly understood questions.
Therefore, squalene biosynthesis genes FARNESYL DIPHOSPHATE SYNTHASE (FPS) and
SQUALENE SYNTHASE (SQS) were engineered via the Nicotiana tabacum chloroplast
(C), nuclear (N) or both (CN) genomes to promote squalene biosynthesis. SQS
levels were ~4300-fold higher in C and CN lines than in N, but all accumulated
~150-fold higher squalene due to substrate or storage limitations. Abnormal leaf
and flower phenotypes, including lower pollen production and reduced fertility,
were observed regardless of the compartment or level of transgene expression.
Substantial changes in metabolomes of all lines were observed: levels of 65-120
unrelated metabolites, including the toxic alkaloid nicotine, changed by as much
as 32-fold. Profound effects of transgenesis on nontarget gene expression
included changes in the abundance of 19 076 transcripts by up to 2000-fold in CN;
7784 transcripts by up to 1400-fold in N; and 5224 transcripts by as much as 2200
fold in C. Transporter-related transcripts were induced, and cell cycle
associated transcripts were disproportionally repressed in all three lines.
Transcriptome changes were validated by qRT-PCR. The mechanism underlying these
large changes likely involves metabolite-mediated anterograde and/or retrograde
signalling irrespective of the level of transgene expression or end product, due
to imbalance of metabolic pools, offering new insight into both anticipated and
unanticipated consequences of metabolic engineering.
PMID- 27507798
TI - Erratum.
PMID- 27507799
TI - Erratum.
PMID- 27507800
TI - Effects of host genetics and environment on egg-associated microbiotas in brown
trout (Salmo trutta).
AB - Recent studies found fish egg-specific bacterial communities that changed over
the course of embryogenesis, suggesting an interaction between the developing
host and its microbiota. Indeed, single-strain infections demonstrated that the
virulence of opportunistic bacteria is influenced by environmental factors and
host immune genes. However, the interplay between a fish embryo host and its
microbiota has not been studied yet at the community level. To test whether host
genetics affects the assemblage of egg-associated bacteria, adult brown trout
(Salmo trutta) were sampled from a natural population. Their gametes were used
for full-factorial in vitro fertilizations to separate sire from dam effects. In
total, 2520 embryos were singly raised under experimental conditions that
differently support microbial growth. High-throughput 16S rRNA amplicon
sequencing was applied to characterize bacterial communities on milt and
fertilized eggs across treatments. Dam and sire identity influenced embryo
mortality, time until hatching and composition of egg-associated microbiotas, but
no link between bacterial communities on milt and on fertilized eggs could be
found. Elevated resources increased embryo mortality and modified bacterial
communities with a shift in their putative functional potential. Resource
availability did not significantly affect any parental effects on embryo
performance. Sire identity affected bacterial diversity that turned out to be a
significant predictor of hatching time: embryos associated with high bacterial
diversity hatched later. We conclude that both host genetics and the availability
of resources define diversity and composition of egg-associated bacterial
communities that then affect the life history of their hosts.
PMID- 27507801
TI - The Role of Hox in Pisiform and Calcaneus Growth Plate Formation and the Nature
of the Zeugopod/Autopod Boundary.
AB - The mesopodium forms at the boundary between the zeugopod and autopod and is
composed of short nodular bones that typically lack growth plates. Hoxa11 and
Hoxa13 are expressed in mutually exclusive proximal-distal domains that demarcate
the zeugopod/autopod boundary. Similarly, Hoxd genes are deployed in two distinct
phases during limb development. The early phase corresponds to proximal segments
including the zeugopod, and a late phase occurs in the digits. This arrangement
produces a gap of low Hoxd expression that is traditionally viewed to correspond
to the mesopodium. In contrast to the other mesopodials, the mammalian pisiform
and calcaneus form true growth plates. We show that these bones, along with other
proximal mesopodials, develop within the Hoxa11 and Hoxd11 expression domains. We
also observe that the pisiform growth plate becomes disorganized with Hoxa11 or
Hoxd11 loss of function, indicating a direct role for Hox11 in its development.
Hoxa13 loss of function has minimal effect on the pisiform and proximal calcaneus
as these bones still form secondary centers and undergo longitudinal growth.
Consideration of the phenotypes resulting from hypodactyly (Hd) and
synpolydactyly homolog (spdh) mutations, which result from altered HOXA13 and
HOXD13 proteins, respectively, confirms that Hox13 plays a limited role in the
development of the pisiform and calcaneus and suggests that they lie within the
early phase of Hox expression. Therefore, with respect to patterns of
ossification and gene expression, these bones share much more in common with the
zeugopod than the autopod. Such an interpretation fits with the timing of autopod
origins during tetrapod evolution.
PMID- 27507802
TI - Testosterone-dependent sex differences in red blood cell hemolysis in storage,
stress, and disease.
AB - BACKGROUND: Red blood cell (RBC) hemolysis represents an intrinsic mechanism for
human vascular disease. Intravascular hemolysis releases hemoglobin and other
metabolites that inhibit nitric oxide signaling and drive oxidative and
inflammatory stress. Although these pathways are important in disease
pathogenesis, genetic and population modifiers of hemolysis, including sex, have
not been established. STUDY DESIGN AND METHODS: We studied sex differences in
storage or stress-induced hemolysis in RBC units from the United States and
Canada in 22 inbred mouse strains and in patients with sickle cell disease (SCD)
using measures of hemolysis in 315 patients who had homozygous SS hemoglobin from
the Walk-PHASST cohort. A mouse model also was used to evaluate posttransfusion
recovery of stored RBCs, and gonadectomy was used to determine the mechanisms
related to sex hormones. RESULTS: An analysis of predisposition to hemolysis
based on sex revealed that male RBCs consistently exhibit increased
susceptibility to hemolysis compared with females in response to routine cold
storage, under osmotic or oxidative stress, after transfusion in mice, and in
patients with SCD. The sex difference is intrinsic to the RBC and is not mediated
by plasmatic factors or female sex hormones. Importantly, orchiectomy in mice
improves RBC storage stability and posttransfusion recovery, whereas testosterone
repletion therapy exacerbates hemolytic response to osmotic or oxidative stress.
CONCLUSION: Our findings suggest that testosterone increases susceptibility to
hemolysis across human diseases, suggesting that male sex may modulate clinical
outcomes in blood storage and SCD and establishing a role for donor genetic
variables in the viability of stored RBCs and in human hemolytic diseases.
PMID- 27507803
TI - Expanding the donor pool: regional variation in pediatric organ donation rates.
AB - There are limited published data on pediatric organ donation rates. The aim of
this study was to describe the trends in pediatric organ donation over time and
to assess the regional variation in pediatric deceased organ donation. OPTN data
were utilized to assess the trends in pediatric organ donation over time. The
number of deceased pediatric organ donors was indexed using regional mortality
data obtained from the National Center for Health Statistics and compared across
UNOS regions and two different eras. The number of pediatric deceased organ
donors has declined in the recent era, largely driven by fewer adolescent donors.
For all age groups, there is significant regional variation in organ donation
rates, with identifiable high- and low-performing regions. Expansion of the donor
pool may be possible by optimizing organ donation in regions demonstrating lower
recruitment of pediatric donors. Using the region with the highest donation rate
for each age group as the gold standard, we estimate a potential 24% increase in
the number of donors if all regions performed comparably, equating to 215 new
pediatric donors annually.
PMID- 27507804
TI - Reduced asthma susceptibility from early childhood exposure to residing in
developing country.
PMID- 27507806
TI - Spontaneous Lung Lesions in Aging Laboratory Rabbits ( Oryctolagus cuniculus).
AB - Spontaneous age-related lesions of laboratory rabbits are not well documented in
the contemporary scientific literature. A retrospective study of diagnostic
necropsies of 36 rabbits >2 years of age found a number of common lung lesions.
Fibromuscular intimal hyperplasia affected medium and to a lesser extent large
pulmonary arteries and was present to a variable extent in all 36 rabbits >2
years of age. The lesions were characterized by fragmentation and/or
reduplication of the internal elastic lamina (IEL), proliferation of
smoothelin+/alpha-smooth muscle actin (alpha-SMA)+/vimentin- smooth muscle cells
and fewer smoothelin-/alpha-SMA+/vimentin+ myofibroblasts, and intimal deposition
of collagen without thrombosis, embolism, or evidence of pulmonary hypertension.
Pulmonary emphysema, present in 30/36 rabbits, was characterized by the loss of
alveolar septa; most affected rabbits did not have clinical signs of respiratory
disease. In 8/13 rabbits of the inbred EIII/JC audiogenic strain, we identified a
unique syndrome of granulomatous pneumonia containing hyaline brown to gray,
globular to ring-like acellular material that was Alcian blue and periodic acid
Schiff positive. The material was immunoreactive for surfactant protein-A and had
the ultrastructural appearance of multilamellar vesicles, suggesting a genetic
defect in surfactant metabolism. Additionally, we found small benign primary lung
tumors (fibropapillomas, 5 rabbits) not previously described. Other findings
included heterotopic bone (5 rabbits), subacute to chronic suppurative
bronchopneumonia, pyogranulomatous pneumonia with plant material, and pulmonary
artifacts from barbiturate euthanasia solution.
PMID- 27507805
TI - Nomenclature for factors of the HLA system, update June 2016.
PMID- 27507807
TI - Care-Seeking Behavior After Notification Among Young Women With Recurrent
Sexually Transmitted Infections After Pelvic Inflammatory Disease.
AB - Objective To determine the level of nurse case management and outreach required
to notify young women with sexually transmitted infection (STI) positive test
results after pelvic inflammatory disease (PID) and percent seeking treatment.
METHODS: Participants (N = 153) were enrolled in a clinical trial of young women
diagnosed with PID and followed for 3 months for recurrent STIs. Vaginal swabs
were obtained at 1 and 3 months. All participants were notified of positive STIs
at 1 and 3 months and treatment arranged. Data were analyzed with logistic
regression for comparison of treatment status by number of nurse contacts.
Results Over the 3-month period, 59 participants (38.6%) tested positive for one
or more STIs and all received notification. Only 50% (19/38) of participants with
STI at 1 month and 43% (16/37) at 3 months received treatment. Conclusions
Despite the high notification rate of positive test results for young adults with
recurrent STIs, many failed to seek treatment.
PMID- 27507808
TI - Understanding the Use of Whole Milk and Flavored Powders in Children of Low
Income, Immigrant Latina Mothers: A Descriptive Study.
PMID- 27507809
TI - Pregnancy outcomes, reproductive history and cardiovascular disease risk in
women: What do we know and what is needed?
PMID- 27507810
TI - Activation of Epidermal Growth Factor Receptor in Macrophages Mediates Feedback
Inhibition of M2 Polarization and Gastrointestinal Tumor Cell Growth.
AB - EGF receptor (EGFR) in tumor cells serves as a tumor promoter. However,
information about EGFR activation in macrophages in regulating M2 polarization
and tumor development is limited. This study aimed to investigate the effects of
EGFR activation in macrophages on M2 polarization and development of
gastrointestinal tumors. IL-4, a cytokine to elicit M2 polarization, stimulated
release of an EGFR ligand, HB-EGF, and transactivation and down-regulation of
EGFR in Raw 264.7 cells and peritoneal macrophages from WT mice. Knockdown of HB
EGF in macrophages inhibited EGFR transactivation by IL-4. IL-4-stimulated STAT6
activation, Arg1 and YM1 gene expression, and HB-EGF production were further
enhanced by inhibition of EGFR activity in Raw 264.7 cells using an EGFR kinase
inhibitor and in peritoneal macrophages from Egfr(wa5) mice with kinase inactive
EGFR and by knockdown of EGFR in peritoneal macrophages from Egfr(fl/fl) LysM-Cre
mice with myeloid cell-specific EGFR deletion. Chitin induced a higher level of
M2 polarization in peritoneal macrophages in Egfr(fl/fl) LysM-Cre mice than that
in Egfr(fl/fl) mice. Accordingly, IL-4-conditioned medium stimulated growth and
epithelial-to-mesenchymal transition in gastric epithelial and colonic tumor
cells, which were suppressed by that from Raw 264.7 cells with HB-EGF knockdown
but promoted by that from Egfr(wa5) and Egfr(fl/fl) LysM-Cre peritoneal
macrophages. Clinical assessment revealed that the number of macrophages with
EGFR expression became less, indicating decreased inhibitory effects on M2
polarization, in late stage of human gastric cancers. Thus, IL-4-stimulated HB
EGF-dependent transactivation of EGFR in macrophages may mediate inhibitory
feedback for M2 polarization and HB-EGF production, thereby inhibiting
gastrointestinal tumor growth.
PMID- 27507811
TI - Interaction of Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) and
Vav3 in the Receptor Activator of Nuclear Factor kappaB (RANK) Signaling Complex
Enhances Osteoclastogenesis.
AB - The signaling pathway downstream of stimulation of receptor activator of nuclear
factor kappaB (RANK) by RANK ligand is crucial for osteoclastogenesis. RANK
recruits TNF receptor-associated factor 6 (TRAF6) to TRAF6-binding sites (T6BSs)
in the RANK cytoplasmic tail (RANKcyto) to trigger downstream osteoclastogenic
signaling cascades. RANKcyto harbors an additional highly conserved domain (HCR)
that also activates crucial signaling during RANK-mediated osteoclastogenesis.
However, the functional cross-talk between T6BSs and the HCR in the RANK
signaling complex remains unclear. To characterize the cross-talk between T6BSs
and the HCR, we screened TRAF6-interacting proteins using a proteomics approach.
We identified Vav3 as a novel TRAF6 binding partner and evaluated the functional
importance of the TRAF6-Vav3 interaction in the RANK signaling complex. We
demonstrated that the coiled-coil domain of TRAF6 interacts directly with the Dbl
homology domain of Vav3 to form the RANK signaling complex independent of the
TRAF6 ubiquitination pathway. TRAF6 is recruited to the RANKcyto mutant, which
lacks T6BSs, via the Vav3 interaction; conversely, Vav3 is recruited to the
RANKcyto mutant, which lacks the IVVY motif, via the TRAF6 interaction. Finally,
we determined that the TRAF6-Vav3 interaction resulting from cross-talk between
T6BSs and the IVVY motif in RANKcyto enhances downstream NF-kappaB, MAPK, and
NFATc1 activation by further strengthening TRAF6 signaling, thereby inducing RANK
mediated osteoclastogenesis. Thus, Vav3 is a novel TRAF6 interaction partner that
functions in the activation of cooperative signaling between T6BSs and the IVVY
motif in the RANK signaling complex.
PMID- 27507812
TI - Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated
Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and
Macrophages via the Proteasome.
AB - Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines
IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through
insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2
macrophages correlate with disease severity and poor lung function, although the
mechanisms that regulate M2 polarization are not understood. Following IL-4
exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human
monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine
phosphorylation and enhanced M2 differentiation, although siRNA knockdown of
SOCS3 did not affect either. By co-immunoprecipitation, we found that SOCS1
complexes with IRS-2 at baseline, and this association increased after IL-4
stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of
proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal
inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of
IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited
ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect
on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals
revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic
cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes
displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic
monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key
negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our
findings provide novel insight into how dysregulated expression of SOCS increases
IL-4 responses in allergic monocytes, and this may represent a new therapeutic
avenue for managing allergic disease.
PMID- 27507813
TI - Leucine Carboxyl Methyltransferase 1 (LCMT-1) Methylates Protein Phosphatase 4
(PP4) and Protein Phosphatase 6 (PP6) and Differentially Regulates the Stable
Formation of Different PP4 Holoenzymes.
AB - The protein phosphatase 2A (PP2A) subfamily of phosphatases, PP2A, PP4, and PP6,
are multifunctional serine/threonine protein phosphatases involved in many
cellular processes. Carboxyl methylation of the PP2A catalytic subunit (PP2Ac) C
terminal leucine is regulated by the opposing activities of leucine carboxyl
methyltransferase 1 (LCMT-1) and protein phosphatase methylesterase 1 (PME-1) and
regulates PP2A holoenzyme formation. The site of methylation on PP2Ac is
conserved in the catalytic subunits of PP4 and PP6, and PP4 is also methylated on
that site, but the identities of the methyltransferase enzyme for PP4 are not
known. Whether PP6 is methylated is also not known. Here we use antibodies
specific for the unmethylated phosphatases to show that PP6 is carboxyl
methylated and that LCMT-1 is the major methyltransferase for PP2A, PP4, and PP6
in mouse embryonic fibroblasts (MEFs). Analysis of PP2A and PP4 complexes by blue
native polyacrylamide gel electrophoresis (BN-PAGE) indicates that PP4 holoenzyme
complexes, like those of PP2A, are differentially regulated by LCMT-1, with the
PP4 regulatory subunit 1 (PP4R1)-containing PP4 complex being the most
dramatically affected by the LCMT-1 loss. MEFs derived from LCMT-1 knock-out
mouse embryos have reduced levels of PP2A B regulatory subunit and PP4R1 relative
to control MEFs, indicating that LCMT-1 is important for maintaining normal
levels of these subunits. Finally, LCMT-1 homozygous knock-out MEFs exhibited
hyperphosphorylation of HDAC3, a reported target of the methylation-dependent
PP4R1-PP4c complex. Collectively, our data suggest that LCMT-1 coordinately
regulates the carboxyl methylation of PP2A-related phosphatases and,
consequently, their holoenzyme assembly and function.
PMID- 27507814
TI - Allostery Wiring Map for Kinesin Energy Transduction and Its Evolution.
AB - How signals between the kinesin active and cytoskeletal binding sites are
transmitted is an open question and an allosteric question. By extracting
correlated evolutionary changes within 700+ sequences, we built a model of
residues that are energetically coupled and that define molecular routes for
signal transmission. Typically, these coupled residues are located at multiple
distal sites and thus are predicted to form a complex, non-linear network that
wires together different functional sites in the protein. Of note, our model
connected the site for ATP hydrolysis with sites that ultimately utilize its free
energy, such as the microtubule-binding site, drug-binding loop 5, and
necklinker. To confirm the calculated energetic connectivity between non-adjacent
residues, double-mutant cycle analysis was conducted with 22 kinesin mutants.
There was a direct correlation between thermodynamic coupling in experiment and
evolutionarily derived energetic coupling. We conclude that energy transduction
is coordinated by multiple distal sites in the protein rather than only being
relayed through adjacent residues. Moreover, this allosteric map forecasts how
energetic orchestration gives rise to different nanomotor behaviors within the
superfamily.
PMID- 27507815
TI - Smoking history can influence the epigenetic and gene expression profile.
PMID- 27507816
TI - Response to comments by Emma et al.
PMID- 27507817
TI - Corrigendum.
PMID- 27507818
TI - Role of the mobility of antigen binding site in high affinity antibody elucidated
by surface plasmon resonance.
AB - Antibody is known to exhibit conformational change in the antigen recognition
site after forming the initial complex. This structural change, which is widely
known as "induced fit", is believed to be critical for high affinity (Kd of nM
range) of antigen-antibody interaction. Elucidation of this 'induced fit' process
is essential for rational design of high affinity antibody, while it is prevented
by limitation of the available biophysical and biochemical data of the initial
complex. Here, we performed kinetic and thermodynamic analysis of the interaction
between single-chain variable fragment (denoted as scFv) of 64M5 antibody and a
(6-4) photoproduct by using surface plasmon resonance (denoted as SPR). It
revealed that the 64M5scFv associates the (6-4) photoproduct at initial step by
hydrophobic interactions, and enthalpy-driving interactions, hydrogen bonds and
van der Waals interactions, were formed by second step structural rearrangement.
Furthermore, mutational analysis revealed that the mobility of the antigen
binding site is critical for the second step. It could be assumed that
optimization of the mobility of the antigen recognition site is a clue for
rational design of high affinity antibody.
PMID- 27507819
TI - Derivation of a valid momentary first-order rate constant for kinetic and
energetic analyses of enzymatic reactions.
AB - To analyze enzymatic reactions energetically for comparison with non-enzymatic
reactions (first order) under the same dimension, a method to derive valid
momentary first-order rate constants for enzymatic reactions was developed. The
momentary first-order rate constant, k enz0 = k cat[E'S']e,0/[S]0, was derived
for an enzymatic reaction under a certain condition. It was shown that this rate
constant is applicable for a wide range of enzymatic reactions. Utilizing this
constant, one can conduct reliable kinetic and energetic analyses of enzymatic
reactions.
PMID- 27507820
TI - Substance Abuse and Addiction Among Ex-Service Personnel: Forces in Mind Trust
Issues Call for Research Proposals.
PMID- 27507821
TI - Trends in Alcohol Use among Adolescents from 2000 to 2011: The Role of
Socioeconomic Status and Depression.
AB - AIMS: To assess temporal trends of adolescent alcohol use in Finland from 2000 to
2011, according to socio-economic status and depression. METHODS: Classroom self
administered questionnaires concerning health, health behaviours and school
experiences were administered biennially from 2000-2001 to 2010-2011 to
nationwide samples of 14- to 16-year-olds (n = 618,084). Alcohol use was measured
as the frequencies of drinking and drunkenness. Socioeconomic status was measured
using parental education and unemployment. Depression was measured using a
Finnish modification of the Beck Depression Inventory. Cross-tabulations and a
logistic regression analysis were applied. RESULTS: Over the study period, rates
of frequent drinking and frequent drunkenness decreased among both boys and
girls. Low levels of parental education and unemployment as well as adolescent
depression increased the likelihoods of frequent drinking and drunkenness. Unlike
the general decreasing trend observed for alcohol use, the likelihoods of
frequent drinking and drunkenness increased among adolescents who were depressed
and had unemployed parents with low levels of education. The prevalence of
frequent drunkenness was 75.8% among the boys in this group during 2008-2011,
whereas the corresponding prevalence was 2.3% for boys without depression and
with highly educated, employed parents. The corresponding figures for girls were
41.7% and 1.4%, respectively. CONCLUSIONS: The overall decreasing trend in
frequent alcohol use was not observed among socioeconomically deprived
adolescents with depression. Thus, alcohol prevention programmes should treat
these youth as special targets.
PMID- 27507822
TI - Population Pharmacokinetics and Pharmacodynamics of Praziquantel in Ugandan
Children with Intestinal Schistosomiasis: Higher Dosages Are Required for Maximal
Efficacy.
AB - Each year, millions of African children receive praziquantel (PZQ) by mass drug
administration (MDA) to treat schistosomiasis at a standard single dose of 40
mg/kg of body weight, a direct extrapolation from studies of adults. A higher
dose of 60 mg/kg is also acceptable for refractory cases. We conducted the first
PZQ pharmacokinetic (PK) and pharmacodynamic (PD) study in young children
comparing dosing. Sixty Ugandan children aged 3 to 8 years old with egg patent
Schistosoma mansoni received PZQ at either 40 mg/kg or 60 mg/kg. PK parameters of
PZQ racemate and enantiomers (R and S) were quantified. PD outcomes were assessed
by standard fecal egg counts and novel schistosome-specific serum (circulating
anodic antigen [CAA]) and urine (circulating cathodic antigen [CCA]) antigen
assays. Population PK and PD analyses were performed to estimate drug exposure in
individual children, and the relationship between drug exposure and
parasitological cure was estimated using logistic regression. Monte Carlo
simulations were performed to identify better, future dosing regimens. There was
marked PK variability between children, but the area under the concentration-time
curve (AUC) of PZQ was strongly predictive of the parasitological cure rate (CR).
Although no child achieved antigenic cure, which is suggestive of an important
residual adult worm burden, higher AUC was associated with greater CAA antigenic
decline at 24 days. To optimize the performance of PZQ, analysis of our
simulations suggest that higher doses (>60 mg/kg) are needed, particularly in
smaller children. IMPORTANCE: Schistosomiasis is a neglected tropical disease,
typically associated with chronic morbidity, and its control is a global health
priority. Praziquantel (PZQ) is the only available antiparasitic drug and is
often given out, as a single oral dose (40 mg/kg), to school-aged children by
mass drug administration (MDA) schemes operating within preventive chemotherapy
campaigns as endorsed by the World Health Organization (WHO). This current
strategy has several limitations. (i) It excludes preschool children who can be
patently infected. (ii) It delivers PZQ at a dose directly extrapolated from
adult pharmacological studies. To address these problems, we conducted the first
pharmacokinetic and pharmacodynamic study of young children within an area of
Uganda where Schistosoma mansoni is hyperendemic. Our results demonstrate that a
higher dose (>60 mg/kg) is required, especially in smaller children, and draw
attention to the need for further optimization of PZQ treatment based on
schistosome antigenic assays, which are more sensitive to pharmacodynamic
markers.
PMID- 27507823
TI - A Diguanylate Cyclase Acts as a Cell Division Inhibitor in a Two-Step Response to
Reductive and Envelope Stresses.
AB - Cell division arrest is a universal checkpoint in response to environmental
assaults that generate cellular stress. In bacteria, the cyclic di-GMP (c-di-GMP)
signaling network is one of several signal transduction systems that regulate key
processes in response to extra-/intracellular stimuli. Here, we find that the
diguanylate cyclase YfiN acts as a bifunctional protein that produces c-di-GMP in
response to reductive stress and then dynamically relocates to the division site
to arrest cell division in response to envelope stress in Escherichia coli YfiN
localizes to the Z ring by interacting with early division proteins and stalls
cell division by preventing the initiation of septal peptidoglycan synthesis.
These studies reveal a new role for a diguanylate cyclase in responding to
environmental change, as well as a novel mechanism for arresting cell division.
IMPORTANCE: While the major role of c-di-GMP signaling is to control the decision
to move freely or settle in a biofilm, recent studies show a broader range of
output functions for c-di-GMP signaling. This work reports an unexpected second
role for YfiN, a conserved diguanylate cyclase in Gram-negative bacteria, known
to contribute to persistence in the host. We find that YfiN acts as a cell
division inhibitor in response to envelope stress. Unlike known cell division
inhibitors, the interaction of YfiN with cell division proteins retains the Z
ring at the midcell but prevents septal invagination. The new function of YfiN
not only emphasizes the versatility of c-di-GMP signaling but describes a novel
mechanism for a cell division checkpoint.
PMID- 27507824
TI - ATP-Dependent C-F Bond Cleavage Allows the Complete Degradation of 4
Fluoroaromatics without Oxygen.
AB - Complete biodegradation of the abundant and persistent fluoroaromatics requires
enzymatic cleavage of an arylic C-F bond, probably the most stable single bond of
a biodegradable organic molecule. While in aerobic microorganisms defluorination
of fluoroaromatics is initiated by oxygenases, arylic C-F bond cleavage has never
been observed in the absence of oxygen. Here, an oxygen-independent enzymatic
aryl fluoride bond cleavage is described during the complete degradation of 4
fluorobenzoate or 4-fluorotoluene to CO2 and HF in the denitrifying Thauera
aromatica: the ATP-dependent defluorination of 4-fluorobenzoyl-coenzyme A (4-F
BzCoA) to benzoyl-coenzyme A (BzCoA) and HF, catalyzed by class I BzCoA reductase
(BCR). Adaptation to growth with the fluoroaromatics was accomplished by the
downregulation of a promiscuous benzoate-CoA ligase and the concomitant
upregulation of 4-F-BzCoA-defluorinating/dearomatizing BCR on the transcriptional
level. We propose an unprecedented mechanism for reductive arylic C-F bond
cleavage via a Birch reduction-like mechanism resulting in a formal nucleophilic
aromatic substitution. In the proposed anionic 4-fluorodienoyl-CoA transition
state, fluoride elimination to BzCoA is favored over protonation to a fluorinated
cyclic dienoyl-CoA. IMPORTANCE: Organofluorides are produced as pesticides,
pharmaceuticals, and other chemicals and comprise approximately one quarter of
all organic compounds in the pharmaceutical and agricultural sectors; they are
considered a growing class of environmentally relevant persistent pollutants.
Especially in the case of fluoroaromatics, biodegradation is hampered by the
extreme stability of the arylic C-F bond. In aerobic microorganisms, degradation
proceeds via oxygenase-dependent C-F bond cleavage reactions, whereas the enzymes
involved in the degradation of fluoroaromatics at anoxic sites are unknown. Here
we report a strategy for the complete biodegradation of a fluoroaromatic to CO2
and HF in a denitrifying bacterium via activation to a CoA ester, followed by
oxygen-independent arylic C-F bond cleavage catalyzed by an ATP-dependent enzyme.
This reaction, in conjunction with a transcriptional adaptation to fluorinated
growth substrates, is essential for the anoxic biodegradation of 4
fluorobenzoate/4-F-toluene and probably other fluoroaromatics.
PMID- 27507825
TI - Localization of the Houdinisome (Ejection Proteins) inside the Bacteriophage P22
Virion by Bubblegram Imaging.
AB - The P22 capsid is a T=7 icosahedrally symmetric protein shell with a portal
protein dodecamer at one 5-fold vertex. Extending outwards from that vertex is a
short tail, and putatively extending inwards is a 15-nm-long alpha-helical barrel
formed by the C-terminal domains of portal protein subunits. In addition to the
densely packed genome, the capsid contains three "ejection proteins" (E-proteins
[gp7, gp16, and gp20]) destined to exit from the tightly sealed capsid during the
process of DNA delivery into target cells. We estimated their copy numbers by
quantitative SDS-PAGE as approximately 12 molecules per virion of gp16 and gp7
and 30 copies of gp20. To localize them, we used bubblegram imaging, an
adaptation of cryo-electron microscopy in which gaseous bubbles induced in
proteins by prolonged irradiation are used to map the proteins' locations. We
applied this technique to wild-type P22, a triple mutant lacking all three E
proteins, and three mutants each lacking one E-protein. We conclude that all
three E-proteins are loosely clustered around the portal axis, in the region
displaced radially inwards from the portal crown. The bubblegram data imply that
approximately half of the alpha-helical barrel seen in the portal crystal
structure is disordered in the mature virion, and parts of the disordered region
present binding sites for E-proteins. Thus positioned, the E-proteins are
strategically placed to pass down the shortened barrel and through the portal
ring and the tail, as they exit from the capsid during an infection. IMPORTANCE:
While it has long been appreciated that capsids serve as delivery vehicles for
viral genomes, there is now growing awareness that viruses also deliver proteins
into their host cells. P22 has three such proteins (ejection proteins [E
proteins]), whose initial locations in the virion have remained unknown despite
their copious amounts (total of 2.5 MDa). This study succeeded in localizing them
by the novel technique of bubblegram imaging. The P22 E-proteins are seen to be
distributed around the orifice of the portal barrel. Interestingly, this barrel,
15 nm long in a crystal structure, is only about half as long in situ: the
remaining, disordered, portion appears to present binding sites for E-proteins.
These observations document a spectacular example of a regulatory order-disorder
transition in a supramolecular system and demonstrate the potential of bubblegram
imaging to map the components of other viruses as well as cellular complexes.
PMID- 27507826
TI - Erratum for Fu et al., Ubiquitin-Like Proteasome System Represents a Eukaryotic
Like Pathway for Targeted Proteolysis in Archaea.
PMID- 27507827
TI - Glycomics for Microbes and Microbiologists.
AB - The recent article "Lectin-Glycan Interaction Network-Based Identification of
Host Receptors of Microbial Pathogenic Adhesins" by Ielasi et al. describes a new
development in microbial carbohydrate analysis [Ielasi FS, Alioscha-Perez M,
Donohue D, Claes S, Sahli H, Schols D, Willaert RG, mBio 7(4):e00584-16, 2016,
http://dx.doi.org/10.1128/mbio.00584-16]. Specific carbohydrate ligands have been
identified from the patterns of lectin binding to oligosaccharides printed on a
chip. The new technique links the output to a comprehensive glycan database and
offers a number of data visualization options. The graphs highlight the
occurrence of potential ligands, organized by organism, tissue, and patterns of
association with disease states. The analysis has successfully predicted novel
glycoprotein ligands for microbial lectins, including an interaction of E. coli
FimH with HIV gp120.
PMID- 27507828
TI - The Cell Wall Polymer Lipoteichoic Acid Becomes Nonessential in Staphylococcus
aureus Cells Lacking the ClpX Chaperone.
AB - Lipoteichoic acid (LTA) is an important cell wall component of Gram-positive
bacteria and a promising target for the development of vaccines and antimicrobial
compounds against Staphylococcus aureus Here we demonstrate that mutations in the
conditionally essential ltaS (LTA synthase) gene arise spontaneously in an S.
aureus mutant lacking the ClpX chaperone. A wide variety of ltaS mutations were
selected, and among these, a substantial portion resulted in premature stop
codons and other changes predicted to abolish LtaS synthesis. Consistent with
this assumption, the clpX ltaS double mutants did not produce LTA, and genetic
analyses confirmed that LTA becomes nonessential in the absence of the ClpX
chaperone. In fact, inactivation of ltaS alleviated the severe growth defect
conferred by the clpX deletion. Microscopic analyses showed that the absence of
ClpX partly alleviates the septum placement defects of an LTA-depleted strain,
while other phenotypes typical of LTA-negative S. aureus mutants, including
increased cell size and decreased autolytic activity, are retained. In
conclusion, our results indicate that LTA has an essential role in septum
placement that can be bypassed by inactivating the ClpX chaperone. IMPORTANCE:
Lipoteichoic acid is an essential component of the Staphylococcus aureus cell
envelope and an attractive target for the development of vaccines and
antimicrobials directed against antibiotic-resistant Gram-positive bacteria such
as methicillin-resistant S. aureus and vancomycin-resistant enterococci. In this
study, we showed that the lipoteichoic acid polymer is essential for growth of S.
aureus only as long as the ClpX chaperone is present in the cell. Our results
indicate that lipoteichoic acid and ClpX play opposite roles in a pathway that
controls two key cell division processes in S. aureus, namely, septum formation
and autolytic activity. The discovery of a novel functional connection in the
genetic network that controls cell division in S. aureus may expand the
repertoire of possible strategies to identify compounds or compound combinations
that kill antibiotic-resistant S. aureus.
PMID- 27507829
TI - Host Physiologic Changes Induced by Influenza A Virus Lead to Staphylococcus
aureus Biofilm Dispersion and Transition from Asymptomatic Colonization to
Invasive Disease.
AB - Staphylococcus aureus is a ubiquitous opportunistic human pathogen and a major
health concern worldwide, causing a wide variety of diseases from mild skin
infections to systemic disease. S. aureus is a major source of severe secondary
bacterial pneumonia after influenza A virus infection, which causes widespread
morbidity and mortality. While the phenomenon of secondary bacterial pneumonia is
well established, the mechanisms behind the transition from asymptomatic
colonization to invasive staphylococcal disease following viral infection remains
unknown. In this report, we have shown that S. aureus biofilms, grown on an upper
respiratory epithelial substratum, disperse in response to host physiologic
changes related to viral infection, such as febrile range temperatures, exogenous
ATP, norepinephrine, and increased glucose. Mice that were colonized with S.
aureus and subsequently exposed to these physiologic stimuli or influenza A virus
coinfection developed pronounced pneumonia. This study provides novel insight
into the transition from colonization to invasive disease, providing a better
understanding of the events involved in the pathogenesis of secondary
staphylococcal pneumonia. IMPORTANCE: In this study, we have determined that host
physiologic changes related to influenza A virus infection causes S. aureus to
disperse from a biofilm state. Additionally, we report that these same host
physiologic changes promote S. aureus dissemination from the nasal tissue to the
lungs in an animal model. Furthermore, this study identifies important aspects
involved in the transition of S. aureus from asymptomatic colonization to
pneumonia.
PMID- 27507830
TI - Salmonella Rapidly Regulates Membrane Permeability To Survive Oxidative Stress.
AB - The outer membrane (OM) of Gram-negative bacteria provides protection against
toxic molecules, including reactive oxygen species (ROS). Decreased OM
permeability can promote bacterial survival under harsh circumstances and
protects against antibiotics. To better understand the regulation of OM
permeability, we studied the real-time influx of hydrogen peroxide in Salmonella
bacteria and discovered two novel mechanisms by which they rapidly control OM
permeability. We found that pores in two major OM proteins, OmpA and OmpC, could
be rapidly opened or closed when oxidative stress is encountered and that the
underlying mechanisms rely on the formation of disulfide bonds in the periplasmic
domain of OmpA and TrxA, respectively. Additionally, we found that a Salmonella
mutant showing increased OM permeability was killed more effectively by treatment
with antibiotics. Together, these results demonstrate that Gram-negative bacteria
regulate the influx of ROS for defense against oxidative stress and reveal novel
targets that can be therapeutically targeted to increase bacterial killing by
conventional antibiotics. IMPORTANCE: Pathogenic bacteria have evolved ways to
circumvent inflammatory immune responses. A decrease in bacterial outer membrane
permeability during infection helps protect bacteria from toxic molecules
produced by the host immune system and allows for effective colonization of the
host. In this report, we reveal molecular mechanisms that rapidly alter outer
membrane pores and their permeability in response to hydrogen peroxide and
oxidative stress. These mechanisms are the first examples of pores that are
rapidly opened or closed in response to reactive oxygen species. Moreover, one of
these mechanisms can be targeted to artificially increase membrane permeability
and thereby increase bacterial killing by the antibiotic cefotaxime during in
vitro experiments and in a mouse model of infection. We envision that a better
understanding of the regulation of membrane permeability will lead to new targets
and treatment options for multidrug-resistant infections.
PMID- 27507831
TI - Tidal volume during mouthpiece non-invasive home ventilation: When the choice is
the right answer.
PMID- 27507832
TI - Antibiotic therapy for stable non-CF bronchiectasis in adults - A systematic
review.
AB - To provide an update on efficacy and safety of antibiotic treatments for stable
non-cystic fibrosis (CF) bronchiectasis (BE). Systematic review based on the
Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was
done. Twenty-six studies (1.898 patients) fulfilled the inclusion criteria.
Studies of inhaled tobramycin have revealed conflicting results regarding quality
of life (QoL), exacerbations and admissions, but may result in sputum cultures
negative for Pseudomonas aeruginosa, whereas studies investigating the effect of
inhaled gentamycin have shown positive effects on sputum bacterial density,
decrease in sputum cultures positive for P. aeruginosa, QoL and exacerbation
rate, but no improvement in forced expiratory volume in first second (FEV1). Oral
azithromycin can reduce exacerbations, together with minor improvements in QoL
and FEV1. Furthermore, oral erythromycin reduces exacerbations, but has no effect
on lung function, symptoms or QoL. Inhaled ciprofloxacin may reduce P. aeruginosa
in sputum cultures, but without changes in lung function, exacerbations or QoL.
Although with limited evidence, inhaled colistin may have effects on P.
aeruginosa density, exacerbations and QoL, whereas studies on aztreonam revealed
no significant clinical improvements in the outcomes of interest, including
exacerbation rate. Adverse events, including bronchospasm, have been reported in
association with tobramycin and aztreonam. Several antibiotic treatment regimens
have been shown to improve QoL and exacerbation rate, whereas findings regarding
sputum production, lung function and admissions have been conflicting. Evidence
based treatment algorithms for antibiotic treatment of stable non-CF BE will have
to await large-scale, long-term controlled studies.
PMID- 27507833
TI - Managing fatigue in sarcoidosis - A systematic review of the evidence.
AB - Fatigue is a common manifestation of sarcoidosis, often persisting without
evidence of disease activity. First-line therapies for sarcoidosis have limited
effect on fatigue. This review aimed to assess the treatment options targeting
sarcoidosis-associated fatigue. Medline and Web of Science were searched in
November 2015; the bibliographies of these papers, and relevant review papers,
were also searched. Studies were included if they reported on the efficacy of
interventions (both pharmacological and non-pharmacological) on fatigue scores in
sarcoidosis patients. Eight studies were identified that fulfilled the inclusion
criteria. These studies evaluated six different interventions (infliximab,
adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There
is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)
alphatherapies (adalimumab and infliximab) and neurostimulants (methylphenidate
and armodafinil), but within five of the studies, the risk of bias was high
within most domains and the remaining three studies included only small numbers
of participants and were short in duration. Trial evidence for treating fatigue
as a manifestation of sarcoidosis is limited and requires further investigation.
Anti-TNF-alpha therapies may be beneficial in patients with organ-threatening
disease. Neurostimulants have some trial evidence supporting improvements in
fatigue but further investigation is needed before they can be recommended.
PMID- 27507834
TI - Mouthpiece ventilation: Individualized patient care is the key to success.
PMID- 27507835
TI - Does the COPD assessment test reflect functional status in patients with COPD?
AB - The aim of this study was to investigate whether the chronic obstructive
pulmonary disease (COPD) assessment test (CAT) reflects the functional status of
patients with COPD. Forty-seven patients underwent anthropometric assessment,
spirometry, the 6-minute walk test (6MWT), the Glittre-activity of daily living
(ADL) test (TGlittre), the London Chest ADL (LCADL) scale, and the CAT. The total
score of the CAT correlated with 6MWT distance, TGlittre time spent, and
LCADL%total ( r = -0.56, 0.52, and 0.78, respectively; p < 0.05 for all). There
was significant difference in 6MWT distance (490 +/- 85.4 m vs. 387 +/- 56.8 m),
TGlittre time spent (3.67 +/- 1.07 min vs. 5.03 +/- 1.32 min), and LCADL%total
(24.2 +/- 3.02% vs. 44.4 +/- 13.3%) between the low and high impacts of COPD on
health status (respectively, p < 0.05 for all) as well as in the LCADL%total
between medium and high impact of COPD on health status (31.3 +/- 7.35% vs. 44.4
+/- 13.3%; p = 0.001). In conclusion, the CAT reflects the functional status of
patients with COPD.
PMID- 27507836
TI - Alpha-, Beta-, and Gamma-synuclein Quantification in Cerebrospinal Fluid by
Multiple Reaction Monitoring Reveals Increased Concentrations in Alzheimer's and
Creutzfeldt-Jakob Disease but No Alteration in Synucleinopathies.
AB - alpha-Synuclein (alphaSyn) is a major constituent of proteinaceous aggregates in
neurodegenerative diseases such as Parkinson's disease (PD) and a potential
biomarker candidate for diagnosis and treatment effects. However, studies about
alphaSyn in cerebrospinal fluid (CSF) in diseases are inconsistent and mainly
based on immunological assays. Quantitative information about beta-synuclein
(betaSyn) and gamma-synuclein (gammaSyn) in CSF is not available.Here, we present
an alternative method for the simultaneous quantification of alphaSyn, betaSyn
and gammaSyn in CSF by multiple reaction monitoring (MRM) with a high sequence
coverage (70%) of alphaSyn to validate previous, ELISA-based results and
characterize synucleins in CSF in more detail.The MRM has high sensitivity in the
low pg/ml range (3-30pg/ml full-length alphaSyn) using 200 MUl CSF. A high
portion of CSF alphaSyn is present in the N-terminally acetylated form and the
concentration of unmodified peptides in the nonamyloid component region is about
40% lower than in the N-terminal region. Synuclein concentrations show a high
correlation with each other in CSF (r>0.80) and in contrast to alphaSyn and
gammaSyn, betaSyn is not affected by blood contamination. CSF alphaSyn, betaSyn
and gammaSyn concentrations were increased in Alzheimer's and Creutzfeldt-Jakob
disease but not altered in PD, PD dementia (PDD), Lewy body dementia and atypical
parkinsonian syndromes. The ratio betaSyn/alphaSyn was increased in PDD (1.49 +/-
0.38, p < 0.05) compared with PD (1.11 +/- 0.26) and controls (1.15 +/- 0.28).
betaSyn shows a high correlation with CSF tau concentrations (r = 0.86, p <
0.0001, n = 125).In conclusion, we could not confirm previous observations of
reduced alphaSyn in PD and our results indicate that CSF synuclein concentrations
are rather general markers of synaptic degeneration than specific for
synucleinopathies. betasyn is an attractive biomarker candidate that might be
used as an alternative to or in combination with tau in AD and CJD diagnosis and
in combination with alphaSyn it is a biomarker candidate for PDD.
PMID- 27507838
TI - Niche divergence between diploid and autotetraploid Tolmiea.
AB - PREMISE OF STUDY: Polyploidy is common in eukaryotes and is of major evolutionary
importance over both short and long time-scales. Compared to allopolyploids,
autopolyploids remain understudied; they are often morphologically cryptic and
frequently remain taxonomically unrecognized, although there is increasing
recognition of the high frequency of autopolyploidy in angiosperms. While
autopolyploidy can serve as an instant speciation mechanism, little is known
about the ecological consequences of this process. We describe the ecological
divergence of a diploid-autotetraploid species pair in Tolmiea. METHODS: We
investigated whether abiotic niche divergence has shaped the current allopatric
distribution of diploid T. diplomenziesii and its autotetraploid derivative, T.
menziesii, in the Pacific Northwest of North America. We employed field measures
of light availability, as well as niche modeling and a principal component
analysis of environmental space. Within a common garden, we also investigated
physiological responses to changes in soil moisture. KEY RESULTS: Diploid and
autotetraploid Tolmiea inhabit significantly different climatic niche spaces. The
climatic niche divergence between these two species is best explained by a shift
in precipitation availability, and we found evidence of differing physiological
response to water availability between these species. CONCLUSIONS: We found that
spatial segregation of T. diplomenziesii and T. menziesii was accompanied by
adaptation to changes in climatic regime. Tolmiea menziesii is not a nascent
autotetraploid, having persisted long enough to be established throughout the
Pacific Northwest, and therefore both polyploidization and subsequent evolution
have contributed to the observed differences between T. menziesii and T.
diplomenziesii.
PMID- 27507839
TI - Bet-hedging against larval herbivory and seed bank mortality in the evolution of
heterocarpy.
AB - PREMISE OF THE STUDY: Bet-hedging strategies maximize long-term geometric fitness
at the cost of reduced arithmetic fitness by offsetting different mortality
risks. Heterocarpic systems accomplish bet-hedging through the production of two
or more fruit types that vary in dormancy and dispersal ability. It is unknown
whether heterocarpy also offsets predispersal mortality risks. To address this
question, we investigated whether heterocarpy in Grindelia ciliata (Asteraceae)
also offsets mortality risks posed by a seed predator Schinia mortua (Noctuidae)
to increase plant fitness. METHODS: We conducted two manipulative experiments to
quantify critical life history components of this plant-insect interaction. We
measured predispersal achene mortality from herbivory, postdispersal achene
mortality in the seed bank, and seedling emergence. These measurements were then
used in deterministic models to evaluate evolutionary consequences of
predispersal seed mortality in G. ciliata. KEY RESULTS: Dormant achene types were
less vulnerable to herbivory but more susceptible to mortality in the seed bank
due to delayed seed emergence. Nondormant achene types experienced high
predispersal mortality but low seed bank mortality due to rapid germination. Our
herbivore-dependent model improved fit between observed and expected proportions
of dormant and nondormant G. ciliata achenes and showed that heterocarpy could
evolve in the absence of postgermination mortality. CONCLUSIONS: Our study
provides empirical support of how predispersal herbivory can be equally important
to postdispersal seed mortality risks in the evolution and maintenance of a
heterocarpic reproductive system and expands understanding of how bet-hedging
theory can be used to understand this unique reproductive strategy.
PMID- 27507840
TI - Life History of the Oldest Lentivirus: Characterization of ELVgv Integrations in
the Dermopteran Genome.
AB - Endogenous retroviruses are genomic elements formed by germline infiltration by
originally exogenous viruses. These molecular fossils provide valuable
information about the evolution of the retroviral family. Lentiviruses are an
extensively studied genus of retroviruses infecting a broad range of mammals.
Despite a wealth of information on their modern evolution, little is known about
their origins. This is partially due to the scarcity of their endogenous forms.
Recently, an endogenous lentivirus, ELVgv, was discovered in the genome of the
Malayan colugo (order Dermoptera). This represents the oldest lentiviral evidence
available and promises to lead to further insights into the history of this
genus. In this study, we analyzed ELVgv integrations at several genomic locations
in four distinct colugo specimens covering all the extant dermopteran species. We
confirmed ELVgv integrations in all the specimens examined, which implies that
the virus originated before the dermopteran diversification. Using a locus
specific dermopteran substitution rate, we estimated that the proviral
integrations occurred 21-40 Ma. Using phylogenetic analysis, we estimated that
ELVgv invaded an ancestor of today's Dermoptera in an even more distant past. We
also provide evidence of selective pressure on the TRIM5 antiviral restriction
factor, something usually taken as indirect evidence of past retroviral
infections. Interestingly, we show that TRIM5 was under strong positive selection
pressure only in the common dermopteran ancestor, where the ELVgv endogenization
occurred. Further experiments are required to determine whether ELVgv
participated in the TRIM5 selection.
PMID- 27507841
TI - The Telltale Heart of Chordate Evolution: New Study Shows Model Organism Making
Do with Less.
PMID- 27507842
TI - Use of cefovecin in a UK population of cats attending first-opinion practices as
recorded in electronic health records.
AB - Objectives The objective was to use electronic health records to describe the use
of cefovecin (Convenia; Zoetis UK), a third-generation long-acting injectable
antimicrobial, in a UK population of cats attending first-opinion practices, and
to compare the use of Convenia with the licensed uses described on the UK
Convenia datasheet. Methods Data were obtained as an Excel database from the
Small Animal Veterinary Surveillance Network for all feline consultations
containing the word Convenia and/or cefovecin from 1 September 2012 to 23
September 2013 inclusive. Entries were classified according to body system
treated, confirmation or suspicion of an abscess, evidence of microbiological
evaluation being performed, any concurrent therapies given and whether any reason
was given for use of Convenia over alternative antimicrobials. Data were exported
to IBM SPSS Statistics and descriptive analysis performed. Results In total, 1148
entries were analysed. The most common body system treated was skin in 553
(48.2%) entries, then urinary (n = 157; 13.7%) and respiratory (n = 112; 9.8%).
Microbiological evaluation was recorded in 193 (16.8%) entries, with visible
purulent material most commonly cited (in 147 [12.8%] entries). A reason for
prescribing Convenia over alternative antimicrobials was given in 138 (12.0%)
entries; the most cited was an inability to orally medicate the cat in 77 (55.8%)
of these entries. Excluding 131 entries where no body system or multiple body
systems were described, the use of Convenia complied with a licensed use in the
UK datasheet in 710 (69.8%) of 1017 entries. Conclusions and relevance Most
administrations were licensed uses; however, most entries did not describe any
microbiological evaluation, or a reason for prescribing Convenia over alternative
antimicrobials. Further education of the public and the veterinary profession is
needed to promote antimicrobial stewardship in the UK. Health records provide a
valuable tool with which to monitor, both locally and at scale, the use of
important therapeutics like antimicrobials. Information relevant to decision
making should be recorded in individual animal health records.
PMID- 27507843
TI - The Influence of Meniscal and Anterolateral Capsular Injury on Knee Laxity in
Patients With Anterior Cruciate Ligament Injuries.
AB - BACKGROUND: The role of the anterolateral capsule (ALC) as a secondary restraint
to quantitative rotatory laxity of patients with an anterior cruciate ligament
(ACL) injury is currently debated. PURPOSE/HYPOTHESIS: The purpose was to
determine the influence of concomitant ALC injuries as well as injuries to other
soft tissue structures on rotatory knee laxity in patients with an ACL injury. It
was hypothesized that a concomitant ALC injury would be associated with increased
rotatory knee laxity as measured during a quantitative pivot-shift test. STUDY
DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Forty-one patients
with an ACL injury (average age, 23 +/- 6.9 years) were enrolled. Two blinded
musculoskeletal radiologists reviewed magnetic resonance imaging (MRI) scans for
the presence of ACL injuries and concomitant soft tissue injuries including the
ALC, medial collateral ligament, lateral collateral ligament, posterolateral
corner, medial meniscus, and lateral meniscus. A standardized pivot-shift test
was performed under anesthesia, and rotatory laxity was quantified according to
anterior translation of the lateral tibial compartment during the pivot-shift
maneuver. The Student t test was used to analyze the data. Statistical
significance was set at P < .05. RESULTS: A complete ACL rupture was confirmed in
all of the patients. MRI evidence of an ALC injury was observed in 21 (51%) of
the patients. Patients with MRI evidence of an ALC injury had significantly
higher rotatory knee laxity (3.6 +/- 1.5 mm) compared with those without an ALC
injury (2.7 +/- 1.5 mm; P = .04). Lateral and medial meniscus injuries were
detected in 17 (41%) and 19 (46%) patients, respectively. Patients with MRI
evidence of either a medial meniscus injury or lateral meniscus injury had
significantly higher rotatory knee laxity compared with patients without these
injuries (medial meniscus: 3.7 +/- 1.4 mm vs 2.7 +/- 1.6 mm, respectively;
lateral meniscus: 3.7 +/- 1.7 mm vs 2.7 +/- 1.3 mm, respectively) (P = .03 for
both). CONCLUSION: MRI evidence of a concomitant injury to the ALC, medial
meniscus, or lateral meniscus is associated with increased knee rotatory laxity
in patients with an ACL injury. These structures may function as important
secondary stabilizers in an ACL-injured knee. Careful assessment and proper
treatment of injuries to these secondary stabilizers should be considered,
especially in knees with a high level of the pivot shift.
PMID- 27507844
TI - Clinical and Ultrasonographic Evaluations of the Shoulders of Elite Swimmers.
AB - BACKGROUND: Shoulder pain is a common problem in competitive swimmers, but the
structural alterations in elite-level competitive swimmers are not well known.
HYPOTHESIS: Adaptive changes are common in the rotator cuff, bursa, labrum, and
capsule in elite swimmers, and such abnormalities are related to factors
concerning training and correlate with symptoms. STUDY DESIGN: Cross-sectional
study; Level of evidence, 3. METHODS: The study population was the 2008 United
States Olympic swimming team. All athletes completed standardized scales on
shoulder pain and function and provided data on their training history and
history of shoulder pain or injuries. Each athlete also underwent a comprehensive
physical examination of both shoulders, followed by an evaluation of the rotator
cuff, biceps, and bursa using ultrasound with dynamic images to assess for
subcoracoid impingement and subacromial impingement. RESULTS: A history of
shoulder pain was reported by 29 of 42 (66%) athletes. Morphological changes
consistent with tendinosis were common in the biceps (33/46 shoulders; 72%) and
supraspinatus/infraspinatus (44/46 shoulders; 96%). Subcoracoid impingement was
seen in 17 of 46 shoulders (37%), with subacromial impingement seen in 34 of 41
shoulders (83%). There was an increased odds ratio (OR) for biceps tendinosis in
older swimmers (OR, 1.92; 95% CI, 1.23-3.00; P = .004) and in swimmers who had
missed a competition because of shoulder pain (OR, 9.76; 95% CI, 1.13-84.3; P =
.038). There was an increased OR for rotator cuff tendinosis in swimmers who
reported worse scores for pain with activities (OR, 0.10; 95% CI, 0.01-0.78; P =
.028) and in those with a positive sulcus sign (OR, 33.2; 95% CI, 3.09-355; P =
.004). There was an increased OR for impingement in swimmers with a positive
sulcus sign (OR, 5.40; 95% CI, 0.80-36.3; P = .083), worse pain scores (OR, 0.44;
95% CI, 0.22-0.87; P = .019), and a partial rotator cuff tear (OR, 31.2; 95% CI,
3.58-272; P = .002). CONCLUSION: We found a high prevalence of rotator cuff and
biceps tendinopathy, which was associated with increased symptoms. Tendinosis was
also more common in swimmers with a positive sulcus sign, suggesting a role for
shoulder laxity.
PMID- 27507845
TI - Effect of Changing the Joint Kinematics of Knees With a Ruptured Anterior
Cruciate Ligament on the Molecular Biological Responses and Spontaneous Healing
in a Rat Model.
AB - BACKGROUND: The poor healing capacity of a completely ruptured anterior cruciate
ligament (ACL) has been attributed to an insufficient vascular supply, cellular
metabolism, and deficient premature scaffold formation because of the unique
intra-articular environment. However, previous studies have focused on intra
articular factors without considering extra-articular factors, including the
biomechanical aspects of ACL-deficient knees. HYPOTHESIS: Changing the joint
kinematics of an ACL-ruptured knee will improve cellular biological responses and
lead to spontaneous healing through the mechanotransduction mechanism. STUDY
DESIGN: Controlled laboratory study. METHODS: A total of 66 skeletally mature
Wistar rats were randomly assigned to a sham-operated group (SO), ACL-transection
group (ACL-T), controlled abnormal movement group (CAM), and an intact group
(IN). The ACL was completely transected at the midportion in the ACL-T and CAM
groups, and the CAM group underwent extra-articular braking to control for
abnormal tibial translation. The SO group underwent skin and joint capsule
incisions and tibial drilling, without ACL transection and extra-articular
braking. The animals were allowed full cage activity until sacrifice at 1, 2, 4,
6, and 8 weeks postoperatively for histological, molecular biological, and
biomechanical assessment. RESULTS: All injured ACLs in the ACL-T group were not
healed, but those in the CAM group healed spontaneously, showing a typical
ligament healing response. Regarding the molecular biological response, there was
an upregulation of anabolic factors (ie, transforming growth factor-beta) and
downregulation of catabolic factors (ie, matrix metalloproteinase). Examination
of the mechanical properties at 8 weeks after injury showed that >50% of the
strength of the intact ACL had returned. CONCLUSION: Our results suggest that
changing the joint kinematics of knees with a ruptured ACL alters the molecular
biological responses and leads to spontaneous healing. These data support our
hypothesis that the mechanotransduction mechanism mediates molecular responses
and determines whether the ACL will heal. CLINICAL RELEVANCE: Elucidating the
relationship between the mechanotransduction mechanism and healing responses in
knees with completely ruptured ACLs may result in the development of novel
nonsurgical treatment that enables the ACL to spontaneously heal in patients who
are not suitable for reconstruction.
PMID- 27507846
TI - Bridging the gap: the assessment and treatment of adolescent personality disorder
in routine clinical care.
AB - Despite a marked increase in research supporting the assessment, diagnosis and
treatment of personality disorder (PD) in adolescence, clinicians continue to be
reluctant to apply treatment guidelines and psychiatric nomenclature in routine
clinical care. This gap arises from several beliefs: (1) psychiatric nomenclature
does not allow the diagnosis of PD in adolescence; (2) certain features of PD are
normative and not particularly symptomatic of personality disturbance; (3) the
symptoms of PD are better explained by other psychiatric syndromes; (4)
adolescents' personalities are still developing and therefore too unstable to
warrant a PD diagnosis; and (5) because PD is long-lasting, treatment-resistant
and unpopular to treat, it would be stigmatising to label an adolescent with
borderline personality disorder (BPD). In this paper, the empirical evidence
challenging each of these beliefs is evaluated in the hope of providing a
balanced review of the validity of adolescent PD with a specific focus on BPD.
The paper concludes with recommendations on how routine clinical care can
integrate a PD focus.
PMID- 27507847
TI - Does paracetamol in pregnancy cause ADHD and autism?
PMID- 27507848
TI - Articulatory Suppression Effects on Short-term Memory of Signed Digits and
Lexical Items in Hearing Bimodal-Bilingual Adults.
AB - We can gain a better understanding of short-term memory processes by studying
different language codes and modalities. Three experiments were conducted to
investigate: (a) Taiwanese Sign Language (TSL) digit spans in Chinese/TSL hearing
bilinguals (n = 32); (b) American Sign Language (ASL) digit spans in English/ASL
hearing bilinguals (n = 15); and (c) TSL lexical sign spans in Chinese/TSL
hearing bilinguals (n = 22). Articulatory suppression conditions were manipulated
to determine if participants would use a speech- or sign-based code to rehearse
lists of signed items. Results from all 3 experiments showed that oral
suppression significantly reduced spans while manual suppression had no effect,
revealing that participants were using speech-based rehearsal to retain lists of
signed items in short-term memory. In addition, sub-vocal rehearsal using Chinese
facilitated higher digit spans than English even though stimuli were perceived
and recalled using signs. This difference was not found for lexical sign spans.
PMID- 27507849
TI - Effects of EFL Individual Learner Variables on Foreign Language Reading Anxiety
and Metacognitive Reading Strategy Use.
AB - Past research has shown an association between foreign language reading anxiety
and reading strategy. However, individual variables tend to affect foreign
language anxiety and strategy use. The present study examined a hypothesized
model that specified direct and indirect effects among English and foreign
languages readers' distinct variables, including academic level; self-perceived
English level; and satisfaction with reading proficiency, reading anxiety, and
metacognitive awareness of reading strategies. A total of 523 volunteer Taiwanese
college students provided 372 valid responses to a written questionnaire (281
women and 91 men; M age = 19.7 years, SD = 1.1) containing the translated
versions of Foreign Language Reading Anxiety Scale, Survey of Reading Strategies
Inventory, and self-assessment background questionnaire. The results showed that
self-evaluation of reading proficiency did not correlate with academic level and
readers' perceptions. Satisfaction had a direct effect on foreign language
reading anxiety but not on metacognitive awareness of reading strategies. Results
of path analysis demonstrated that the perception learners who had their own
reading proficiency predicted their foreign language reading anxiety and was a
mediating variable for metacognitive reading strategy use.
PMID- 27507851
TI - Knockdown of Apolipoprotein E Enhanced Sensitivity of Hep3B Cells to Cardiac
Steroids via Regulating Na+/K+-ATPase Signalosome.
AB - This study compared the sensitivity of human hepatoma Hep3B, SK-HEP-1, SMMC-7721,
and BEL-7402 cells to cardiac steroids, including bufalin (BF), a bufalin
derivative (BF211), ouabain (OUA), and digitoxin (DIG). Hep3B cells exhibited
relatively low sensitivity to cardiac steroids. Expression levels of subunits of
Na+/K+-ATPase were high in Hep3B cells. However, colocalization of Na+/K+-ATPase
and caveolin was nearly undetectable in Hep3B cells. By using RNA-Seq technology,
we found a total of 36 genes to be differentially expressed between Hep3B cells
and SK-HEP-1 cells, which are highly sensitive to cardiac steroids. Our
bioinformatics analysis determined that these genes were mostly comprised of
extracellular space, protein binding, and extracellular region. Among these 36
genes, apolipoprotein E (APOE) played a critical role, as knockdown APOE
expression induced colocalization of Na+/K+-ATPase and caveolin and increased
sensitivity of Hep3B cells to both proliferation-inhibiting and cytotoxic effects
of BF or BF211. Also, the effects of BF on PI3K/AKT/GSK3beta and apoptosis signal
cascades were enhanced in APOE knockdown cells. The results of our study
confirmed the role of Na+/K+-ATPase signalosome in cytotoxicity of cardiac
steroids and suggested that APOE regulated the sensitivity of cells to cardiac
steroids by affecting formation and function of Na+/K+-ATPase signalosome. In
addition, intercellular interaction with high level of Na+/K+-ATPase beta1
subunit may be also a factor in the low sensitivity of Hep3B cells to cardiac
steroids. Mol Cancer Ther; 15(12); 2955-65. (c)2016 AACR.
PMID- 27507850
TI - EGFR and RB1 as Dual Biomarkers in HPV-Negative Head and Neck Cancer.
AB - Clinical decision making for human papillomavirus (HPV)-negative head and neck
squamous cell carcinoma (HNSCC) is predominantly guided by disease stage and
anatomic location, with few validated biomarkers. The epidermal growth factor
receptor (EGFR) is an important therapeutic target, but its value in guiding
therapeutic decision making remains ambiguous. We integrated analysis of
clinically annotated tissue microarrays with analysis of data available through
the TCGA, to investigate the idea that expression signatures involving EGFR,
proteins regulating EGFR function, and core cell-cycle modulators might serve as
prognostic or drug response-predictive biomarkers. This work suggests that
consideration of the expression of NSDHL and proteins that regulate EGFR
recycling in combination with EGFR provides a useful prognostic biomarker set. In
addition, inactivation of the tumor suppressor retinoblastoma 1 (RB1), reflected
by CCND1/CDK6-inactivating phosphorylation of RB1 at T356, inversely correlated
with expression of EGFR in patient HNSCC samples. Moreover, stratification of
cases with high EGFR by expression levels of CCND1, CDK6, or the CCND1/CDK6
regulatory protein p16 (CDKN2A) identified groups with significant survival
differences. To further explore the relationship between EGFR and RB1-associated
cell-cycle activity, we evaluated simultaneous inhibition of RB1 phosphorylation
with the CDK4/6 inhibitor palbociclib and of EGFR activity with lapatinib or
afatinib. These drug combinations had synergistic inhibitory effects on the
proliferation of HNSCC cells and strikingly limited ERK1/2 phosphorylation in
contrast to either agent used alone. In summary, combinations of CDK and EGFR
inhibitors may be particularly useful in EGFR and pT356RB1-expressing or
CCND1/CDK6-overexpressing HPV-negative HNSCC. Mol Cancer Ther; 15(10); 2486-97.
(c)2016 AACR.
PMID- 27507852
TI - FTY720 (Fingolimod) Inhibits HIF1 and HIF2 Signaling, Promotes Vascular
Remodeling, and Chemosensitizes in Renal Cell Carcinoma Animal Model.
AB - Clear cell renal cell carcinoma (ccRCC) is characterized by intratumoral hypoxia
and chemoresistance. The hypoxia-inducible factors HIF1alpha and HIF2alpha play a
crucial role in ccRCC initiation and progression. We previously identified the
sphingosine kinase 1/sphingosine 1-phosphate (SphK1/S1P) pathway as a new
modulator of HIF1alpha and HIF2alpha under hypoxia in various cancer cell models.
Here, we report that FTY720, an inhibitor of the S1P signaling pathway, inhibits
both HIF1alpha and HIF2alpha accumulation in several human cancer cell lines. In
a ccRCC heterotopic xenograft model, we show that FTY720 transiently decreases
HIF1alpha and HIF2alpha intratumoral level and modifies tumor vessel architecture
within 5 days of treatment, suggesting a vascular normalization. In mice bearing
subcutaneous ccRCC tumor, FTY720 and a gemcitabine-based chemotherapy alone
display a limited effect, whereas, in combination, there is a significant effect
on tumor size without toxicity. Noteworthy, administration of FTY720 for 5 days
before chemotherapy is not associated with a more effective tumor control,
suggesting a mode of action mainly independent of the vascular remodeling. In
conclusion, these findings demonstrate that FTY720 could successfully sensitize
ccRCC to chemotherapy and establish this molecule as a potent therapeutic agent
for ccRCC treatment, independently of drug scheduling. Mol Cancer Ther; 15(10);
2465-74. (c)2016 AACR.
PMID- 27507853
TI - Genomic Landscape of Malignant Mesotheliomas.
AB - Understanding the genomic landscape of malignant mesothelioma may identify novel
molecular drivers of this ultra-rare disease, which can lead to an expanded
roster of targeted therapies and clinical trial options for patients with
mesothelioma. We examined the molecular profiles of 42 patients with malignant
mesothelioma (including pleural, peritoneal, and pericardial) that were referred
by clinicians to be tested in a Clinical Laboratory Improvement Amendments (CLIA)
laboratory using next-generation sequencing (NGS; 182 or 236 genes). Among 42
patients, there were 116 alterations, with 92 being distinct. The number of
genomic alterations per patient ranged from 1 to 5 (median = 3). No two patients
had identical molecular portfolios. The most common aberrations were in BAP1
(BRCA1-associated protein 1; 47.6% [20/42]), NF2 (38.1% [16/42]), and CDKN2A/B
(loss) (35.7% [15/42]). BAP1 alterations and CDKN2A/B loss were associated with
pleural mesothelioma (OR 3.4, P = 0.059 [BAP1] [trend]; OR 5.8, P = 0.01
[CDKN2A/B]). All 42 patients had a molecular abnormality that was potentially
actionable (median = three actionable alterations per patient; range, 1 to 5),
and, in 40 patients (95.2%), a drug approved by the FDA was applicable. In
conclusion, each individual with malignant mesothelioma harbored a unique set of
genomic aberrations, suggesting that NGS-based profiling of patients will be
needed if patients are to be optimally matched to cognate treatments. All 42
patients had at least one alteration that was, in theory, pharmacologically
tractable. Mol Cancer Ther; 15(10); 2498-507. (c)2016 AACR.
PMID- 27507854
TI - CREBH Couples Circadian Clock With Hepatic Lipid Metabolism.
AB - The circadian clock orchestrates diverse physiological processes critical for
health and disease. CREB, hepatocyte specific (CREBH) is a liver-enriched,
endoplasmic reticulum (ER)-tethered transcription factor known to regulate the
hepatic acute phase response and energy homeostasis under stress conditions. We
demonstrate that CREBH is regulated by the circadian clock and functions as a
circadian regulator of hepatic lipid metabolism. Proteolytic activation of CREBH
in the liver exhibits typical circadian rhythmicity controlled by the core clock
oscillator BMAL1 and AKT/glycogen synthase kinase 3beta (GSK3beta) signaling
pathway. GSK3beta-mediated phosphorylation of CREBH modulates the association
between CREBH and the coat protein complex II transport vesicle and thus controls
the ER-to-Golgi transport and subsequent proteolytic cleavage of CREBH in a
circadian manner. Functionally, CREBH regulates circadian expression of the key
genes involved in triglyceride (TG) and fatty acid (FA) metabolism and is
required to maintain circadian amplitudes of blood TG and FA in mice. During the
circadian cycle, CREBH rhythmically regulates and interacts with the hepatic
nuclear receptors peroxisome proliferator-activated receptor alpha and liver X
receptor alpha as well as with the circadian oscillation activator DBP and the
repressor E4BP4 to modulate CREBH transcriptional activities. In conclusion,
these studies reveal that CREBH functions as a circadian-regulated liver
transcriptional regulator that integrates energy metabolism with circadian
rhythm.
PMID- 27507855
TI - Adult Playfulness, Humor Styles, and Subjective Happiness.
AB - Playfulness has been referred to as a disposition that involves reframing a
situation to amuse others and to make the situation more stimulating and
enjoyable. It may serve to shift one's perspective when dealing with
environmental threats. Despite all the benefits of playfulness towards
psychological well-being, it remains a largely understudied subject in
psychology, particularly in Chinese societies. Hence, this study examined the
association between adult playfulness, humor styles, and subjective happiness
among a sample of 166 university students in Hong Kong and 159 students in
Guangzhou, who completed a self-administered questionnaire, including the Short
Measure for Adult Playfulness, the Chinese Humor Styles Questionnaire, and the
Subjective Happiness Scale. Results showed that adult playfulness was positively
correlated with affiliative humor, self-enhancing humor, and subjective happiness
in both Hong Kong and Guangzhou samples. By its implication, highly playful
Chinese students preferred using affiliative and self-enhancing humor to amuse
themselves and others.
PMID- 27507857
TI - Often Overlooked but Critical: Poststroke Cognitive Impairment in Right
Hemispheric Ischemic Stroke.
PMID- 27507856
TI - Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes:
A Pooled Analysis of 9 Trials.
AB - BACKGROUND: Thrombolytic therapy with intravenous alteplase within 4.5 hours of
ischemic stroke onset increases the overall likelihood of an excellent outcome
(no, or nondisabling, symptoms). Any improvement in functional outcome
distribution has value, and herein we provide an assessment of the effect of
alteplase on the distribution of the functional level by treatment delay, age,
and stroke severity. METHODS: Prespecified pooled analysis of 6756 patients from
9 randomized trials comparing alteplase versus placebo/open control. Ordinal
logistic regression models assessed treatment differences after adjustment for
treatment delay, age, stroke severity, and relevant interaction term(s). RESULTS:
Treatment with alteplase was beneficial for a delay in treatment extending to 4.5
hours after stroke onset, with a greater benefit with earlier treatment. Neither
age nor stroke severity significantly influenced the slope of the relationship
between benefit and time to treatment initiation. For the observed case mix of
patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes),
the net absolute benefit from alteplase (ie, the difference between those who
would do better if given alteplase and those who would do worse) was 55 patients
per 1000 treated (95% confidence interval, 13-91; P=0.004). CONCLUSIONS:
Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset
increases the chance of achieving an improved level of function for all patients
across the age spectrum, including the over 80s and across all severities of
stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that
treatment is initiated, the greater the benefit.
PMID- 27507858
TI - Automated CT Perfusion Ischemic Core Volume and Noncontrast CT ASPECTS (Alberta
Stroke Program Early CT Score): Correlation and Clinical Outcome Prediction in
Large Vessel Stroke.
AB - BACKGROUND AND PURPOSE: The semiquantitative noncontrast CT Alberta Stroke
Program Early CT Score (ASPECTS) and RAPID automated computed tomography (CT)
perfusion (CTP) ischemic core volumetric measurements have been used to quantify
infarct extent. We aim to determine the correlation between ASPECTS and CTP
ischemic core, evaluate the variability of core volumes within ASPECTS strata,
and assess the strength of their association with clinical outcomes. METHODS:
Review of a prospective, single-center database of consecutive thrombectomies of
middle cerebral or intracranial internal carotid artery occlusions with
pretreatment CTP between September 2010 and September 2015. CTP was processed
with RAPID software to identify ischemic core (relative cerebral blood flow<30%
of normal tissue). RESULTS: Three hundred and thirty-two patients fulfilled
inclusion criteria. Median age was 66 years (55-75), median ASPECTS was 8 (7-9),
whereas median CTP ischemic core was 11 cc (2-27). Median time from last normal
to groin puncture was 5.8 hours (3.9-8.8), and 90-day modified Rankin scale score
0 to 2 was observed in 54%. The correlation between CTP ischemic core and ASPECTS
was fair (R=-0.36; P<0.01). Twenty-six patients (8%) had ASPECTS <6 and CTP core
<=50 cc (37% had modified Rankin scale score 0-2, whereas 29% were deceased at 90
days). Conversely, 27 patients (8%) had CTP core >50 cc and ASPECTS >=6 (29% had
modified Rankin scale 0-2, whereas 21% were deceased at 90 days). Moderate
correlations between ASPECTS and final infarct volume (R=-0.42; P<0.01) and
between CTP ischemic core and final infarct volume (R=0.50; P<0.01) were
observed; coefficients were not significantly influenced by the time from stroke
onset to presentation. Multivariable regression indicated ASPECTS >=6 (odds ratio
4.10; 95% confidence interval, 1.47-11.46; P=0.01) and CTP core <=50 cc (odds
ratio 3.86; 95% confidence interval, 1.22-12.15; P=0.02) independently and
comparably predictive of good outcome. CONCLUSIONS: There is wide variability of
CTP-derived core volumes within ASPECTS strata. Patient selection may be affected
by the imaging selection method.
PMID- 27507859
TI - Risk Stratification for Recurrence and Mortality in Embolic Stroke of
Undetermined Source.
AB - BACKGROUND AND PURPOSE: The risk of stroke recurrence in patients with Embolic
Stroke of Undetermined Source (ESUS) is high, and the optimal antithrombotic
strategy for secondary prevention is unclear. We investigated whether congestive
heart failure, hypertension, age >=75 years, diabetes mellitus, and stroke or
transient ischemic attack (TIA; CHADS2) and CHA2DS2-VASc scores can stratify the
long-term risk of ischemic stroke/TIA recurrence and death in ESUS. METHODS: We
pooled data sets of 11 stroke registries from Europe and America. ESUS was
defined according to the Cryptogenic Stroke/ESUS International Working Group. Cox
regression analyses were performed to investigate if prestroke CHADS2 and
congestive heart failure, hypertension, age >=75 years, diabetes mellitus, stroke
or TIA, vascular disease, age 65-74 years, sex category (CHA2DS2-VASc) scores
were independently associated with the risk of ischemic stroke/TIA recurrence or
death. The Kaplan-Meier product limit method was used to estimate the cumulative
probability of ischemic stroke/TIA recurrence and death in different strata of
the CHADS2 and CHA2DS2-VASc scores. RESULTS: One hundred fifty-nine (5.6% per
year) ischemic stroke/TIA recurrences and 148 (5.2% per year) deaths occurred in
1095 patients (median age, 68 years) followed-up for a median of 31 months.
Compared with CHADS2 score 0, patients with CHADS2 score 1 and CHADS2 score >1
had higher risk of ischemic stroke/TIA recurrence (hazard ratio [HR], 2.38; 95%
confidence interval [CI], 1.41-4.00 and HR, 2.72; 95% CI, 1.68-4.40,
respectively) and death (HR, 3.58; 95% CI, 1.80-7.12, and HR, 5.45; 95% CI, 2.86
10.40, respectively). Compared with low-risk CHA2DS2-VASc score, patients with
high-risk CHA2DS2-VASc score had higher risk of ischemic stroke/TIA recurrence
(HR, 3.35; 95% CI, 1.94-5.80) and death (HR, 13.0; 95% CI, 4.7-35.4).
CONCLUSIONS: The risk of recurrent ischemic stroke/TIA and death in ESUS is
reliably stratified by CHADS2 and CHA2DS2-VASc scores. Compared with the low-risk
group, patients in the high-risk CHA2DS2-VASc group have much higher risk of
ischemic stroke recurrence/TIA and death, approximately 3-fold and 13-fold,
respectively.
PMID- 27507861
TI - Nonatheroscleotic Isolated Middle Cerebral Artery Disease May Be Early
Manifestation of Moyamoya Disease.
AB - BACKGROUND AND PURPOSE: Middle cerebral artery steno-occlusive disease (MCAD) is
not an uncommon cause of ischemic stroke in young Asians. Aside from
atherosclerosis, the pathogenesis of MCAD include various nonatherosclerotic
vasculopathies, most of which are yet to be defined. This study investigated the
pathogenesis of symptomatic isolated MCAD in young Asian patients using high
resolution magnetic resonance imaging (HR-MRI) and mutation analysis of RNF213.
METHODS: Patients aged <60 years with stroke or transient ischemic attack caused
by MCAD were prospectively enrolled. Patients with a confirmed diagnosis of
moyamoya disease, dissection, and vasculitis; with significant steno-occlusion in
cerebral arteries other than the MCA; or with high-risk cardioembolic source were
excluded. Using high-resolution MRI, patients were classified into an
atherosclerosis group and a nonatherosclerosis group. RESULTS: Eighty-one
patients were enrolled, 45 (56.6%) in the atherosclerosis and 36 (44.4%) in the
nonatherosclerosis group. The nonatherosclerosis group was significantly younger
(P=0.013), had a smaller number of vascular risk factors (P=0.001), showed a
lower homocysteine level (P<0.001), thinner intima-media thickness (P=0.006), and
had more frequent heterozygotes at RNF213 (P=0.045) than the atherosclerosis
group. Diffusion-weighted image lesion pattern showed no significant differences
in assumed stroke mechanisms between the 2 groups. CONCLUSIONS:
Nonatherosclerotic pathogenesis are common in young Asians with symptomatic
isolated MCAD. Clinical findings, high-resolution MRI features, and results of
RNF213 mutation analysis suggest that moyamoya disease is responsible
etiologically for a significant portion of nonatherosclerotic lesions.
Symptomatic isolated MCAD may be an early manifestation of moyamoya disease in
young Asian adults.
PMID- 27507860
TI - Global Survey of the Frequency of Atrial Fibrillation-Associated Stroke: Embolic
Stroke of Undetermined Source Global Registry.
AB - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is increasingly recognized as
the single most important cause of disabling ischemic stroke in the elderly. We
undertook an international survey to characterize the frequency of AF-associated
stroke, methods of AF detection, and patient features. METHODS: Consecutive
patients hospitalized for ischemic stroke in 2013 to 2014 were surveyed from 19
stroke research centers in 19 different countries. Data were analyzed by global
regions and World Bank income levels. RESULTS: Of 2144 patients with ischemic
stroke, 590 (28%; 95% confidence interval, 25.6-29.5) had AF-associated stroke,
with highest frequencies in North America (35%) and Europe (33%) and lowest in
Latin America (17%). Most had a history of AF before stroke (15%) or newly
detected AF on electrocardiography (10%); only 2% of patients with ischemic
stroke had unsuspected AF detected by poststroke cardiac rhythm monitoring. The
mean age and 30-day mortality rate of patients with AF-associated stroke (75
years; SD, 11.5 years; 10%; 95% confidence interval, 7.6-12.6, respectively) were
substantially higher than those of patients without AF (64 years; SD, 15.58
years; 4%; 95% confidence interval, 3.3-5.4; P<0.001 for both comparisons). There
was a strong positive correlation between the mean age and the frequency of AF
(r=0.76; P=0.0002). CONCLUSIONS: This cross-sectional global sample of patients
with recent ischemic stroke shows a substantial frequency of AF-associated stroke
throughout the world in proportion to the mean age of the stroke population. Most
AF is identified by history or electrocardiography; the yield of conventional
short-duration cardiac rhythm monitoring is relatively low. Patients with AF
associated stroke were typically elderly (>75 years old) and more often women.
PMID- 27507862
TI - Association Between Serum Phosphate Levels and Stroke Risk in Patients Undergoing
Hemodialysis: The Q-Cohort Study.
AB - BACKGROUND AND PURPOSE: The contribution of serum phosphate levels to stroke risk
in dialysis patients remains unclear. The present study aimed to elucidate the
respective association between serum phosphate levels and the risk of brain
hemorrhage or infarction in patients undergoing hemodialysis. METHODS: A total of
3437 patients undergoing hemodialysis were followed up for a median of 3.9 years.
The primary outcome was the occurrence of brain hemorrhage or infarction.
Patients were divided into 4 groups based on their baseline serum phosphate
levels (Q1-Q4). Stroke risk was estimated using a Cox proportional hazards model.
RESULTS: During the follow-up period, 75 patients experienced brain hemorrhage
and 139 experienced brain infarction. The risk of brain hemorrhage was
significantly higher in the highest (Q4) compared with the lowest quartile (Q1)
as the reference value (multivariate-adjusted hazard ratio [95% confidence
intervals]: Q1, 1.00; Q2, 1.76 [0.79-4.18]; Q3, 1.99 [0.92-4.67]; and Q4, 2.74
[1.27-6.47]; P=0.077 for trend; hazard ratio for every 1 mmol/L increase in serum
phosphate level, 2.07 [1.10-3.81]; P=0.025). In contrast, the risk of brain
infarction was significantly higher in Q1 (P=0.045) compared with Q3 as the
reference value (Q1, 1.65 [1.01-2.73]; Q2, 1.35 [0.82-2.25]; Q3, 1.00; and Q4,
1.30 [0.77-2.20]). CONCLUSIONS: Higher serum phosphate levels were associated
with an increased risk of brain hemorrhage, whereas low levels were associated
with an increased risk of brain infarction in hemodialysis patients. These
results suggest the importance of managing serum phosphate levels within an
appropriate range in hemodialysis patients. CLINICAL TRIAL REGISTRATION: URL:
http://www.umin.ac.jp/. Unique identifier: UMIN000000556.
PMID- 27507863
TI - Cerebral Microbleeds and Cortical Superficial Siderosis in Patients Presenting
With Minor Cerebrovascular Events.
AB - BACKGROUND AND PURPOSE: Transient focal neurological episodes occur in cerebral
amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Risk
factors and outcomes of minor ischemic stroke or TIA might differ in patients
with and without cerebral microbleeds (CMBs), including CAA-consistent lobar CMB.
METHODS: Baseline magnetic resonance imaging (MRI) was analyzed for CMBs and
cortical superficial siderosis in 416 patients in the prospective computed
tomography and MRI in the CATCH study (Triage of TIA and Minor Cerebrovascular
Events to Identify High Risk Patients). Clinical symptoms, baseline
characteristics, recurrence, and 90-day modified Rankin Scale were prospectively
collected. MRI white-matter hyperintensity was measured using the Fazekas scale.
RESULTS: CMBs were detected in 65 (15.6%) and cortical superficial siderosis in
11 patients (2.6%). Lobar CMBs were present in 49 (11.8%). In multivariable
logistic regression adjusted for risk factors and age, subcortical Fazekas score
was associated with lobar CMB (odds ratio, 2.07; 95% confidence interval, 1.23
3.48; P=0.006). Forty-two patients (10.1%) had lobar-only CMBs with or without
cortical superficial siderosis consistent with modified Boston criteria for
possible/probable CAA. The possible/probable CAA pattern was not predictive of
recurrent TIA (odds ratio, 0.42; 95% confidence interval, 0.05-3.31; P=0.41),
stroke (odds ratio, 1.24; 95% confidence interval, 0.26-5.99; P=0.79), or 90-day
modified Rankin Scale score >=2 (odds ratio, 1.38; 95% confidence interval, 0.62
3.07; P=0.42). CONCLUSIONS: CMBs in TIA and minor stroke are moderately common
but do not predict recurrence or 90-day outcome. CAA-related transient focal
neurological episodes and TIA have overlapping clinical symptoms, suggesting that
MRI may be needed for differentiation.
PMID- 27507864
TI - Comparison of Perfusion CT Software to Predict the Final Infarct Volume After
Thrombectomy.
AB - BACKGROUND AND PURPOSE: Computed tomographic perfusion represents an interesting
physiological imaging modality to select patients for reperfusion therapy in
acute ischemic stroke. The purpose of our study was to determine the accuracy of
different commercial perfusion CT software packages (Philips (A), Siemens (B),
and RAPID (C)) to predict the final infarct volume (FIV) after mechanical
thrombectomy. METHODS: Single-institutional computed tomographic perfusion data
from 147 mechanically recanalized acute ischemic stroke patients were
postprocessed. Ischemic core and FIV were compared about thrombolysis in cerebral
infarction (TICI) score and time interval to reperfusion. FIV was measured at
follow-up imaging between days 1 and 8 after stroke. RESULTS: In 118 successfully
recanalized patients (TICI 2b/3), a moderately to strongly positive correlation
was observed between ischemic core and FIV. The highest accuracy and best
correlation are shown in early and fully recanalized patients (Pearson r for
A=0.42, B=0.64, and C=0.83; P<0.001). Bland-Altman plots and boxplots demonstrate
smaller ranges in package C than in A and B. Significant differences were found
between the packages about over- and underestimation of the ischemic core.
Package A, compared with B and C, estimated more than twice as many patients with
a malignant stroke profile (P<0.001). Package C best predicted hypoperfusion
volume in nonsuccessfully recanalized patients. CONCLUSIONS: Our study
demonstrates best accuracy and approximation between the results of a fully
automated software (RAPID) and FIV, especially in early and fully recanalized
patients. Furthermore, this software package overestimated the FIV to a
significantly lower degree and estimated a malignant mismatch profile less often
than other software.
PMID- 27507865
TI - Affective Prosody and Depression After Stroke: A Pilot Study.
AB - BACKGROUND AND PURPOSE: Poststroke depression (PSD) is a frequent complication of
stroke with detrimental consequences in terms of quality of life and functional
outcomes. In individuals with major depression, several studies have demonstrated
an alteration of affective prosody. The aim of this study is to identify prosodic
markers that may be predictive of PSD. METHODS: Patient voices were recorded at
baseline and 3 months after stroke. We extracted prosodic parameters, including
fundamental frequency, percentage of voice breaks, and shimmer. Depression and
anxiety symptoms were assessed 3 months later. RESULTS: Among the 49 patients
included in the study, 22.5% developed PSD 3 months after stroke. A significant
decrease was observed concerning the fundamental frequency among patients who
developed PSD. Discriminant analysis demonstrated that initial voice breaks
coupled with shimmer are strongly predictive of subsequent PSD. CONCLUSIONS:
Early alterations of affective prosody are associated with a higher risk of PSD 3
months after a stroke. This new physiological approach overcomes traditional
barriers associated with clinical instruments and contributes to the prediction
of this disorder.
PMID- 27507866
TI - Does Admission to Hospital Affect Trends in Survival and Dependency After Stroke
Using the South London Stroke Register?
AB - BACKGROUND AND PURPOSE: Despite guidelines for specialist assessment in hospital
for stroke, it is important to identify patient characteristics, trends, and
outcome in patients not admitted to hospital compared with patients admitted to
hospital. METHODS: Population-based stroke register of first in a life time
strokes between 1995 and 2012 were examined. Baseline data included admission or
nonadmission, case mix, stroke subtype, and risk factors before stroke. Survival
curves were estimated with Kaplan-Meier methods. Logistic regression was used to
determine factors associated with poor outcome (dead and dependency: Barthel
index, <15) at 3 months and 1 year. RESULTS: Three thousand four hundred sixty
four patients were admitted to hospital for stroke. Patients admitted were more
likely have more severe impairments (P<0.001). There was a significant trend for
increasing admission over time; 1995 to 2000 (82%), 2001 to 2006 (90%), and 2007
to 2012 (94%); P<0.001. When survival analysis was stratified according to
Barthel index >=15 at day 7, there were no significant differences in survival
curves between admission and nonadmission groups in 1995 to 2000 (P=0.15) or 2001
to 2006 (P=0.06), but there was a significant trend for higher survival rates for
nonadmission in the 2007 to 2012 cohort (P=0.025). Admission to hospital (stroke
unit) compared with nonadmission was also associated with poor outcome in the
2001 to 2006 time period (odds ratio, 2.66; confidence interval, 1.17-6.04) and
the 2007 to 2012 time period (odds ratio, 5.26; confidence interval, 1.27-21.81).
CONCLUSION: There is a survival advantage from 2007 onward and lower levels of
dependency from 2001 onward after adjusting for case mix for those patients who
are not admitted to hospital, which requires further explanation.
PMID- 27507867
TI - Impact of Initial Diffusion-Weighted Imaging Lesion Growth Rate on the Success of
Endovascular Reperfusion Therapy.
AB - BACKGROUND AND PURPOSE: Initial diffusion-weighted imaging lesion growth rate
(IGR) assessed by diffusion-weighted imaging lesion volume divided by the delay
from onset to magnetic resonance imaging offers an estimate of early brain
infarction progression. We investigated the impact of IGR on the rate of
favorable outcome according to the occurrence of a successful endovascular
revascularization within 6 hours after onset in patients experiencing an acute
brain infarction complicating internal carotid artery terminus/middle cerebral
artery M1 occlusion. METHODS: The primary study end point was a favorable outcome
defined by a modified Rankin Scale score of <=2, 90 days after onset. A
Thrombolysis in Cerebral Infarction score 2b/3 defined a successful
recanalization. RESULTS: A total of 166 patients were included. Median IGR was 7
mL/h (interquartile range, 2-26). Sixty-eight patients (41%) experienced a
favorable outcome. After adjustment on age, systolic blood pressure, vessel site
occlusion, National Institutes of Health Stroke Scale, and antithrombotic
medication, increase in IGR was associated with a decreased occurrence of
favorable outcome with an odds ratio per SD increase of 0.60 (95% confidence
interval, 0.38-0.94; P=0.03). A successful recanalization was achieved among 56%
of the patients after a median delay of 251 minutes (interquartile range, 211-291
minutes). Increasing IGR was associated with a decreased favorable outcome only
when a successful recanalization was not achieved (adjusted odds ratio, 0.32; 95%
confidence interval, 0.12-0.85; P=0.02). CONCLUSIONS: Proximal internal carotid
artery/M1 occlusion did result into a wide range of IGR within 6 hours after
onset. Increasing IGR was associated with a lower rate of favorable outcome after
endovascular treatment overall and when a successful recanalization was not
achieved.
PMID- 27507868
TI - Prescription of Guideline-Based Medical Therapies at Discharge After Carotid
Artery Stenting and Endarterectomy: An NCDR Analysis.
AB - BACKGROUND AND PURPOSE: Carotid artery revascularization was previously found to
incrementally reduce stroke risk among patients with carotid stenosis treated
with medical therapy. However, the frequency with which optimal medical therapies
are used at discharge after carotid endarterectomy (CEA) and carotid artery
stenting (CAS) is not known, and the influence of patient, operator, and hospital
characteristics on the likelihood of prescription is poorly understood. METHODS:
In a retrospective cohort study of 23 112 patients undergoing CAS or CEA between
January 2007 and June 2012 at US hospitals participating in the CARE registry
(Carotid Artery Revascularization and Endarterectomy), we examined antiplatelet
therapy and statin utilization at discharge. Hierarchical multivariable logistic
regression was used in adjusted analyses. RESULTS: Antiplatelet agents and
statins were prescribed at discharge in 99% and 78%, respectively, after CAS and
93% and 75%, respectively, after CEA. After adjustment, antiplatelet therapy was
more often prescribed after CAS than CEA (odds ratio 2.4 [95% confidence interval
1.68-3.45]), but statin prescription was equally likely (odds ratio 1.11 [95%
confidence interval 0.84-1.49]). Operator specialty (medical>radiology/surgery)
and hospital community setting (suburban>urban>rural) independently predicted
antiplatelet and statin agent use at discharge, whereas hospital geographic
location (Northeast>Midwest/South>West) predicted use of statins but not
antiplatelet therapy at discharge. CONCLUSIONS: US antiplatelet agent and statin
discharge prescription rates were suboptimal after both CAS and CEA and varied by
revascularization modality, operating physician specialty, and hospital
characteristics. Improved and more uniform utilization after these procedures
will be critical to the success of comprehensive stroke risk reduction efforts.
PMID- 27507869
TI - Large Capacity of Conscious Access for Incidental Memories in Natural Scenes.
AB - When searching a crowd, people can detect a target face only by direct fixation
and attention. Once the target is found, it is consciously experienced and
remembered, but what is the perceptual fate of the fixated nontarget faces?
Whereas introspection suggests that one may remember nontargets, previous studies
have proposed that almost no memory should be retained. Using a gaze-contingent
paradigm, we asked subjects to visually search for a target face within a crowded
natural scene and then tested their memory for nontarget faces, as well as their
confidence in those memories. Subjects remembered up to seven fixated, nontarget
faces with more than 70% accuracy. Memory accuracy was correlated with trial-by
trial confidence ratings, which implies that the memory was consciously
maintained and accessed. When the search scene was inverted, no more than three
nontarget faces were remembered. These findings imply that incidental memory for
faces, such as those recalled by eyewitnesses, is more reliable than is usually
assumed.
PMID- 27507870
TI - Healthcare staff attitudes towards the use of electronic cigarettes ('e
cigarettes') compared with a local trust policy.
AB - BACKGROUND: E-cigarette use has risen dramatically in recent years, despite
uncertainty over long-term health effects and concerns regarding efficacy as a
smoking cessation device. Currently, there is no legislation prohibiting use in
public, though many trusts have extended the NHS Smokefree policy to include e
cigarettes. The successful implementation of such policy is, however, unclear.
AIM: This study examined staff attitudes towards the use of e-cigarettes in a
hospital environment with respect to enforcement of a local trust smoking policy.
METHODS: A total of 79 healthcare professionals working at South Tyneside
District Hospital, South Shields, completed a written questionnaire regarding use
of e-cigarettes, particularly views on use in public and on hospital premises.
Factors influencing the likelihood of individuals to challenge the use of e
cigarettes were assessed. RESULTS: In all, 45% of respondents thought that e
cigarettes should be allowed in public places, though a majority (62%) favoured
use on hospital grounds compared to within hospital buildings (18%). Over 50% of
respondents were unaware of trust policy relating to e-cigarettes and only 25%
had ever challenged someone using a device. Roughly, one-third reported that they
would still not challenge someone in future, despite being informed of trust
policy. Fear of abuse was the most cited reason for not challenging. Expressed
concerns of e-cigarette use related to fire risk, 'normalising' smoking behaviour
and uncertainty of long-term effects. CONCLUSION: Most staff do not enforce trust
policy regarding e-cigarette use. This reflects variation in opinion over use,
poor awareness of the policy itself and perceived barriers to implementation,
including fear of abuse. Addressing these issues through staff education sessions
may help successful future implementation.
PMID- 27507871
TI - Restricted Mean Survival Time: An Obligatory End Point for Time-to-Event Analysis
in Cancer Trials?
PMID- 27507872
TI - Critical Role of Iron in Epoetin Alfa Treatment of Chemotherapy-Associated
Anemia.
PMID- 27507873
TI - Intellectual Outcome in Molecular Subgroups of Medulloblastoma.
AB - Purpose To evaluate intellectual functioning and the implications of limiting
radiation exposure in the four biologically distinct subgroups of
medulloblastoma: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4.
Patients and Methods A total of 121 patients with medulloblastoma (n = 51, Group
4; n = 25, Group 3; n = 28, SHH; and n = 17, WNT), who were treated between 1991
and 2013 at the Hospital for Sick Children (Toronto, Ontario, Canada), Children's
National Health System (Washington, DC), or the Lucile Packard Children's
Hospital (Palo Alto, CA), had intellectual assessments. First, we compared
intellectual trajectories between subgroups. Next, we evaluated the effect of
treatment with reduced-dose craniospinal irradiation (CSI) plus a tumor bed boost
versus treatments that deliver higher CSI doses and/or larger boost volumes to
the brain (all other treatments) within subgroups. Linear mixed modeling was used
to determine the stability or change in intelligence scores over time. Results
Intellectual outcomes declined comparably in each subgroup except for processing
speed; SHH declined less than Group 3 ( P = .04). SHH had the lowest incidence of
cerebellar mutism and motor deficits. Treatment with reduced-dose CSI plus a
tumor bed boost was associated with preserved intellectual functioning in WNT and
Group 4 patients considered together (ie, subgroups containing patients who are
candidates for therapy de-escalation), and not in Group 3 or SHH. Across all
subgroups, patients in the all other treatments group declined over time (all P <
.05). Conclusion SHH patients appear to have the most distinct functional (ie,
motor deficits and mutism) outcomes and a unique processing speed trajectory.
Only WNT and Group 4 patients seem to benefit from limiting radiation exposure.
Our findings highlight the value of conducting subgroup-specific analyses, and
can be used to inform novel biologically based treatment protocols for patients
with medulloblastoma.
PMID- 27507874
TI - Randomized Controlled Trial of Laparoscopic Versus Open D2 Distal Gastrectomy for
Advanced Gastric Cancer: How Should We Define the Age of Included Patents?
PMID- 27507875
TI - How to Summarize the Safety Profile of Epoetin Alfa Versus Best Standard of Care
in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy?
PMID- 27507876
TI - Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line
Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With
Activating Epidermal Growth Factor Receptor Mutations.
AB - PURPOSE: To determine whether the addition of pemetrexed to gefitinib (P+G)
provides clinical benefit, compared with gefitinib monotherapy, in patients with
advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC) and activating
epidermal growth factor receptor (EGFR) mutations. PATIENTS AND METHODS:
Chemotherapy-naive for advanced NSCLC patients from China, Japan, Korea, and
Taiwan (35 sites) with advanced, EGFR-mutant, NS NSCLC were randomly assigned
(2:1; computer-generated, interactive voice response) to open-label pemetrexed
(500 mg/m(2) on day 1 of every 21-day cycle) plus gefitinib (250 mg/d [n = 129])
or gefitinib alone (n = 66). The primary end point was progression-free-survival
(PFS); secondary end points were time to progressive disease, overall survival,
tumor response rates, duration of response, and safety. All end points were
assessed in the intent-to-treat and safety population (P+G, n = 126; gefitinib
alone, n = 65). RESULTS: PFS was significantly longer with P+G (median, 15.8
months; 95% CI, 12.6 to 18.3 months) than with gefitinib (median, 10.9 months;
95% CI, 9.7 to 13.8 months; adjusted hazard ratio [HR], 0.68; 95% CI, 0.48 to
0.96; one-sided P = .014; two-sided P = .029). Results of EGFR exon 19 deletion
and EGFR exon 21 L858R point mutation subgroup analyses were consistent with the
intent-to-treat result. P+G, compared with gefitinib alone, resulted in
significantly longer time to progressive disease (median, 16.2 v 10.9 months,
respectively; HR, 0.66; 95% CI, 0.47 to 0.93) and numerically longer duration of
response (median, 15.4 v 11.3 months, respectively; HR, 0.74; 95% CI, 0.50 to
1.08). Tumor response rates did not differ. Overall survival data are immature.
Drug-related grade 3 or 4 adverse events were more common with P+G, but
toxicities were manageable. CONCLUSION: P+G improved PFS compared with gefitinib
alone in East Asian patients with advanced NS NSCLC and activating EGFR
mutations. This combination may offer EGFR mutation-positive patients new
treatment options and improved clinical outcomes compared with the current
standard of care.
PMID- 27507877
TI - Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in
Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory
Acute Leukemia.
AB - Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of
selinexor, a selective inhibitor of nuclear export, when combined with
fludarabine and cytarabine, in children with relapsed or refractory leukemia.
Patients and Methods Eighteen patients with relapsed or refractory acute leukemia
were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for
Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome)
clinical trial (NCT02212561). Selinexor, initially at 30 mg/m2 per dose, was
given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a
rolling-six design. Fludarabine 30 mg/m2 and cytarabine 2 g/m2 were administered
on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on
days 1 and 22. Response evaluations were performed on day 15 and at the
completion of course 1. Results Among the 17 patients who were evaluable for
toxicity, three were treated at 30 mg/m2, three at 40 mg/m2, six at 55 mg/m2, and
five at 70 mg/m2. The most common grade 3 nonhematologic toxicity was
asymptomatic hyponatremia. Two patients who were treated at 70 mg/m2 experienced
reversible cerebellar toxicity, thereby defining the dose-limiting toxicity.
Pharmacokinetic parameters demonstrated that plasma exposure was dose
proportional. Fifteen of 16 patients demonstrated at least a twofold increase of
XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily
pretreated, relapsed, and refractory patients, seven of 15 evaluable patients
(47%) achieved complete response or complete response with incomplete count
recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine,
is tolerable at doses up to 55 mg/m2 in pediatric patients with relapsed or
refractory leukemia. All patients who received selinexor at >= 40 mg/m2
demonstrated XPO1 target inhibition. Response rates are promising and will be
further explored in a phase II trial.
PMID- 27507878
TI - Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell
Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and
Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and
Overall Mortality.
AB - PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one
important treatment option for patients with aggressive adult T-cell
leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was
recently approved as a treatment for ATLL in Japan. Major concerns exist about
the possible adverse effects of pretransplantation Mog because Mog depletes
regulatory T cells for several months. We assessed the impact of
pretransplantation Mog on clinical outcomes after allo-HSCT. PATIENTS AND
METHODS: We included 996 allo-HSCT recipients age 70 years or younger with
aggressive ATLL who were given the diagnosis between 2000 and 2013 and who
received intensive chemotherapy by multiple chemotherapeutic drugs as first-line
therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45
days from the last Mog to allo-HSCT. RESULTS: Pretransplantation Mog was
associated with an increased risk of grade 3 to 4 acute graft-versus-host disease
(GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic
corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative
incidence of nonrelapse mortality was significantly higher in patients with
pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The
probability of 1-year overall survival was also significantly inferior in
patients with pretransplantation Mog compared with those without (32.3% v 49.4%;
P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was
associated with a dismal clinical outcome. CONCLUSION: Pretransplantation Mog was
significantly associated with an increased risk of GVHD-related mortality, which
supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In
clinical practice, Mog should be cautiously used for patients with ATLL who are
eligible for allo-HSCT.
PMID- 27507879
TI - Changes in Clinical Context for Kaposi's Sarcoma and Non-Hodgkin Lymphoma Among
People With HIV Infection in the United States.
AB - PURPOSE: The biology of HIV-associated cancers may differ depending on
immunologic and virologic context during development. Therefore, an understanding
of the burden of Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL) relative to
antiretroviral therapy (ART), virologic suppression, and CD4 count is important.
PATIENTS AND METHODS: KS and NHL diagnoses during 1996 to 2011 were identified
among patients with HIV infection in eight clinical cohorts in the United States.
Among patients in routine HIV clinical care, the proportion of cases in
categories of ART use, HIV RNA, and CD4 count at diagnosis were described across
calendar time. Person-time and incidence rates were calculated for each category.
RESULTS: We identified 466 patients with KS and 258 with NHL. In recent years, KS
was more frequently diagnosed after ART initiation (55% in 1996 to 2001 v 76% in
2007 to 2011; P-trend = .02). The proportion of patients with NHL who received
ART was higher but stable over time (83% overall; P-trend = .81). An increasing
proportion of KS and NHL occurred at higher CD4 counts (P < .05 for KS and NHL)
and with undetectable HIV RNA (P < .05 for KS and NHL). In recent years, more
person-time was contributed by patients who received ART, had high CD4 counts and
had undetectable HIV RNA, whereas incidence rates in these same categories
remained stable or declined. CONCLUSION: Over time, KS and NHL occurred at higher
CD4 counts and lower HIV RNA values, and KS occurred more frequently after ART
initiation. These changes were driven by an increasing proportion of patients
with HIV who received effective ART, had higher CD4 counts, and had suppressed
HIV RNA and not by increases in cancer risk within these subgroups. An improved
understanding of HIV-associated cancer pathogenesis and outcomes in the context
of successful ART is therefore important.
PMID- 27507880
TI - Reply to T. Hasegawa et al and I. Gross et al.
PMID- 27507881
TI - Reply to L. Zong et al.
PMID- 27507882
TI - MEF2D-BCL9 Fusion Gene Is Associated With High-Risk Acute B-Cell Precursor
Lymphoblastic Leukemia in Adolescents.
AB - PURPOSE: Acute lymphoblastic leukemia (ALL) makes up a significant proportion of
all pediatric cancers, and relapsed ALL is a leading cause of cancer-associated
deaths in children. Identification of risk factors and druggable molecular
targets in ALL can lead to a better stratification of treatments and subsequent
improvement in prognosis. PATIENTS AND METHODS: We enrolled 59 children with
relapsed or primary refractory ALL who were treated in our institutions. We
primarily performed RNA sequencing (RNA-seq) using patients' leukemic cells to
comprehensively detect gene fusions and analyze gene expression profiles. On the
basis of results obtained by RNA-seq, we performed genetic validation, functional
analysis, and in vitro drug sensitivity testing using patients' samples and an
exogenous expression model. RESULTS: We identified a total of 26 gene fusions in
22 patients by RNA-seq. Among these, 19 were nonrandom gene fusions already
described in ALL, and four of the remaining seven involved identical combination
of MEF2D and BCL9. All MEF2D-BCL9-positive patients had B-cell precursor
immunophenotype and were characterized as being older in age, being resistant to
chemotherapy, having very early relapse, and having leukemic blasts that mimic
morphologically mature B-cell leukemia with markedly high expression of HDAC9.
Exogenous expression of MEF2D-BCL9 in a B-cell precursor ALL cell line promoted
cell growth, increased HDAC9 expression, and induced resistance to dexamethasone.
Using a primary culture of leukemic blasts from a patient, we identified several
molecular targeted drugs that conferred inhibitory effects in vitro. CONCLUSION:
A novel MEF2D-BCL9 fusion we identified characterizes a novel subset of pediatric
ALL, predicts poor prognosis, and may be a candidate for novel molecular
targeting.
PMID- 27507883
TI - Talking to Children With Cancer: Sometimes Less Is More.
PMID- 27507884
TI - Enhanced copy number variants detection from whole-exome sequencing data using
EXCAVATOR2.
AB - Copy Number Variants (CNVs) are structural rearrangements contributing to
phenotypic variation that have been proved to be associated with many disease
states. Over the last years, the identification of CNVs from whole-exome
sequencing (WES) data has become a common practice for research and clinical
purpose and, consequently, the demand for more and more efficient and accurate
methods has increased. In this paper, we demonstrate that more than 30% of WES
data map outside the targeted regions and that these reads, usually discarded,
can be exploited to enhance the identification of CNVs from WES experiments.
Here, we present EXCAVATOR2, the first read count based tool that exploits all
the reads produced by WES experiments to detect CNVs with a genome-wide
resolution. To evaluate the performance of our novel tool we use it for analysing
two WES data sets, a population data set sequenced by the 1000 Genomes Project
and a tumor data set made of bladder cancer samples. The results obtained from
these analyses demonstrate that EXCAVATOR2 outperforms other four state-of-the
art methods and that our combined approach enlarge the spectrum of detectable
CNVs from WES data with an unprecedented resolution. EXCAVATOR2 is freely
available at http://sourceforge.net/projects/excavator2tool/.
PMID- 27507885
TI - ADPriboDB: The database of ADP-ribosylated proteins.
AB - ADP-ribosylation refers to the addition of one or more ADP-ribose units onto
proteins post-translationally. This protein modification is often added by ADP
ribosyltransferases, commonly known as PARPs, but it can also be added by other
enzymes, including sirtuins or bacterial toxins. While past literature has
utilized a variety of methods to identify ADP-ribosylated proteins, recent
proteomics studies bring the power of mass spectrometry to determine sites of the
modification. To appreciate the diverse roles of ADP-ribosylation across the
proteome, we have created ADPriboDB - a database of ADP-ribosylated proteins
(http://ADPriboDB.leunglab.org). Each entry of ADPriboDB is annotated manually by
at least two independent curators from the literature between January 1975 and
July 2015. The current database includes over 12 400 protein entries from 459
publications, identifying 2389 unique proteins. Here, we describe the structure
and the current state of ADPriboDB as well as the criteria for entry inclusion.
Using this aggregate data, we identified a statistically significant enrichment
of ADP-ribosylated proteins in non-membranous RNA granules. To our knowledge,
ADPriboDB is the first publicly available database encapsulating ADP-ribosylated
proteins identified from the past 40 years, with a hope to facilitate the
research of both basic scientists and clinicians to better understand ADP
ribosylation at the molecular level.
PMID- 27507886
TI - Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35
speckle causing its abnormal splicing.
AB - A short abnormal polyalanine expansion in the polyadenylate-binding protein
nuclear-1 (PABPN1) protein causes oculopharyngeal muscular dystrophy (OPMD).
Mutated PABPN1 proteins accumulate as insoluble intranuclear aggregates in
muscles of OPMD patients. While the roles of PABPN1 in nuclear polyadenylation
and regulation of alternative poly(A) site choice have been established, the
molecular mechanisms which trigger pathological defects in OPMD and the role of
aggregates remain to be determined. Using exon array, for the first time we have
identified several splicing defects in OPMD. In particular, we have demonstrated
a defect in the splicing regulation of the muscle-specific Troponin T3 (TNNT3)
mutually exclusive exons 16 and 17 in OPMD samples compared to controls. This
splicing defect is directly linked to the SC35 (SRSF2) splicing factor and to the
presence of nuclear aggregates. As reported here, PABPN1 aggregates are able to
trap TNNT3 pre-mRNA, driving it outside nuclear speckles, leading to an altered
SC35-mediated splicing. This results in a decreased calcium sensitivity of muscle
fibers, which could in turn plays a role in muscle pathology. We thus report a
novel mechanism of alternative splicing deregulation that may play a role in
various other diseases with nuclear inclusions or foci containing an RNA binding
protein.
PMID- 27507887
TI - The RNA-binding protein Gemin5 binds directly to the ribosome and regulates
global translation.
AB - RNA-binding proteins (RBPs) play crucial roles in all organisms. The protein
Gemin5 harbors two functional domains. The N-terminal domain binds to snRNAs
targeting them for snRNPs assembly, while the C-terminal domain binds to IRES
elements through a non-canonical RNA-binding site. Here we report a comprehensive
view of the Gemin5 interactome; most partners copurified with the N-terminal
domain via RNA bridges. Notably, Gemin5 sediments with the subcellular ribosome
fraction, and His-Gemin5 binds to ribosome particles via its N-terminal domain.
The interaction with the ribosome was lost in F381A and Y474A Gemin5 mutants, but
not in W14A and Y15A. Moreover, the ribosomal proteins L3 and L4 bind directly
with Gemin5, and conversely, Gemin5 mutants impairing the binding to the ribosome
are defective in the interaction with L3 and L4. The overall polysome profile was
affected by Gemin5 depletion or overexpression, concomitant to an increase or a
decrease, respectively, of global protein synthesis. Gemin5, and G5-Nter as well,
were detected on the polysome fractions. These results reveal the ribosome
binding capacity of the N-ter moiety, enabling Gemin5 to control global protein
synthesis. Our study uncovers a crosstalk between this protein and the ribosome,
and provides support for the view that Gemin5 may control translation elongation.
PMID- 27507888
TI - Discharging tRNAs: a tug of war between translation and detoxification in
Escherichia coli.
AB - Translation is a central cellular process and is optimized for speed and
fidelity. The speed of translation of a single codon depends on the concentration
of aminoacyl-tRNAs. Here, we used microarray-based approaches to analyze the
charging levels of tRNAs in Escherichia coli growing at different growth rates.
Strikingly, we observed a non-uniform aminoacylation of tRNAs in complex media.
In contrast, in minimal medium, the level of aminoacyl-tRNAs is more uniform and
rises to approximately 60%. Particularly, the charging level of tRNA(Ser),
tRNA(Cys), tRNA(Thr) and tRNA(His) is below 50% in complex medium and their
aminoacylation levels mirror the degree that amino acids inhibit growth when
individually added to minimal medium. Serine is among the most toxic amino acids
for bacteria and tRNAs(Ser) exhibit the lowest charging levels, below 10%, at
high growth rate although intracellular serine concentration is plentiful. As a
result some serine codons are among the most slowly translated codons. A large
fraction of the serine is most likely degraded by L-serine-deaminase, which
competes with the seryl-tRNA-synthetase that charges the tRNAs(Ser) These results
indicate that the level of aminoacylation in complex media might be a competition
between charging for translation and degradation of amino acids that inhibit
growth.
PMID- 27507889
TI - Retraction: Long non-coding RNA INXS is a critical mediator of BCL-XS induced
apoptosis.
PMID- 27507890
TI - Exercise limitation in chronic kidney disease: deep seas and new shores.
PMID- 27507891
TI - Urinary proteomics predict onset of microalbuminuria in normoalbuminuric type 2
diabetic patients, a sub-study of the DIRECT-Protect 2 study.
AB - Background: Early prevention of diabetic nephropathy is not successful as early
interventions have shown conflicting results, partly because of a lack of early
and precise indicators of disease development. Urinary proteomics has shown
promise in this regard and could identify those at high risk who might benefit
from treatment. In this study we investigate its utility in a large type 2
diabetic cohort with normoalbuminuria. Methods: We performed a post hoc analysis
in the Diabetic Retinopathy Candesartan Trials (DIRECT-Protect 2 study), a multi
centric randomized clinical controlled trial. Patients were allocated to
candesartan or placebo, with the aim of slowing the progression of retinopathy.
The secondary endpoint was development of persistent microalbuminuria (three of
four samples). We used a previously defined chronic kidney disease risk score
based on proteomic measurement of 273 urinary peptides (CKD273-classifier). A Cox
regression model for the progression of albuminuria was developed and evaluated
with integrated discrimination improvement (IDI), continuous net reclassification
index (cNRI) and receiver operating characteristic curve statistics. Results:
Seven hundred and thirty-seven patients were analysed and 89 developed persistent
microalbuminuria (12%) with a mean follow-up of 4.1 years. At baseline the CKD273
classifier predicted development of microalbuminuria during follow-up,
independent of treatment (candesartan/placebo), age, gender, systolic blood
pressure, urine albumin excretion rate, estimated glomerular filtration rate,
HbA1c and diabetes duration, with hazard ratio 2.5 [95% confidence interval (CI)
1.4-4.3; P = 0.002] and area under the curve 0.79 (95% CI 0.75-0.84; P < 0.0001).
The CKD273-classifier improved the risk prediction (relative IDI 14%, P = 0.002;
cNRI 0.10, P = 0.043). Conclusions: In this cohort of patients with type 2
diabetes and normoalbuminuria from a large intervention study, the CKD273
classifier was an independent predictor of microalbuminuria. This may help
identify high-risk normoalbuminuric patients for preventive strategies for
diabetic nephropathy.
PMID- 27507892
TI - Characterization of C3 in C3 glomerulopathy.
AB - Background: C3 glomerulopathy (C3G) is caused by overactivity of the alternative
pathway of complement that results in bright glomerular C3 staining with minimal
or no deposition of immunoglobulins on immunofluorescence microscopy. Laser
microdissection and mass spectrometry of the two subtypes, C3 glomerulonephritis
(C3GN) and dense deposit disease (DDD), have identified C3 as the predominant
glomerular complement protein, although lesser amounts of C9, C5, C6, C7 and C8
are detectable. C3 plays a central role in complement activity, with its
proteolytic cleavage first generating C3a and C3b, followed by inactivation of
C3b generating iC3b (which includes C3alpha and C3beta), which undergoes further
breakdown yielding C3c and terminal breakdown fragment C3dg. The composition of
C3 breakdown products in C3G is not known. Methods: In this study, we chose six
cases each of C3GN and DDD to analyze the composition of C3 deposits. We analyzed
the amino acid sequence of C3 spectra detected by mass spectrometry to determine
the relative abundance of C3 fragments in C3G. Thus we were able to determine the
amino acid sequences mapping to the various C3 activation products including
C3dg, C3alpha (C3alpha1 and alpha2), and C3beta that are part of C3b/iC3b/C3c.
Results: C3dg is the predominant cleavage product detected with the highest amino
acid coverage. The remaining amino acids map to C3alpha (C3alpha1 and alpha2) and
C3beta. Amino acids mapping to C3a and C3f are absent. Taken together, the
C3alpha and C3beta amino acids represent iC3b prior to or after C3c cleavage of
C3dg. The C3 spectra for both C3GN and DDD are surprisingly similar. Conclusion:
The finding of large amounts of C3dg suggests that C3b deposition in the
glomerulus is an active process triggered by thioester binding of C3b to the
glycocalyx overlying the glomerular endothelial cells and glomerular basement
membrane. Regulatory protein-mediated inactivation of C3b results in the
generation of iC3b. After additional cleavages, mostly C3dg remains.
PMID- 27507893
TI - Effects of bioaerosol exposure on respiratory health in compost workers: a 13
year follow-up study.
AB - OBJECTIVES: To determine the risk of German compost workers developing chronic
respiratory effects from long-term exposure to bioaerosols. METHODS: Respiratory
health was determined in 74 currently exposed compost workers and 37 non-exposed
controls after 13 years of follow-up. In addition, 42 former compost workers
(drop-outs) who left their work during the follow-up period were also examined.
Respiratory symptoms and working conditions were assessed using identical
questionnaires as at baseline. In addition, lung function was measured using the
same spirometer as in the initial study. Sera from both surveys were tested for
specific IgE and IgG antibodies to moulds and the risk of work-related symptoms
was evaluated using regression approaches for prospective studies with binary
data. RESULTS: In the follow-up period, the number of participants reporting
cough significantly increased in compost workers and drop-outs compared to the
controls. Working as a compost worker for at least 5 years increased the relative
risk for cough (RR 1.28; 95% CI 1.2 to 1.4) and for cough with phlegm (RR 1.32;
95% CI 1.2 to 1.5). Current and former compost workers had slightly lower
predicted percentage of forced expiratory volume in 1 s and predicted percentage
of forced vital capacity than controls, but decrease in lung function during
follow-up was not different among the 3 groups. In addition, no significant
changes could be detected in antibody concentrations. CONCLUSIONS: Our results
suggest that chronic exposure to bioaerosols in composting plants is related to a
significantly higher risk for cough with phlegm, indicating chronic bronchitis.
However, compost workers showed no higher incidence of deterioration of pulmonary
function over the study.
PMID- 27507894
TI - Barriers to Care Coordination and Medical Home Implementation.
AB - BACKGROUND: Pediatricians are central in leading the family-centered medical home
(FCMH), yet little is known about how provider-perceived barriers to and
attitudes toward the FCMH affect implementation. This study aims to assess the
relationship between pediatrician-perceived barriers to and attitudes toward FCMH
and reported care coordination. METHODS: Pediatricians working in ambulatory care
responded to the American Academy of Pediatrics Periodic Survey of Fellows #79 (N
= 572, response rate, 59%). Our primary care coordination outcomes were whether
pediatricians were: (1) leading a multidisciplinary team; (2) developing care
plans; and (3) connecting with support services. Independent variables included
barriers to FCMH implementation (lack of communication skills, support services,
and time). Associations between outcomes and barriers were assessed by
multivariate logistic regression, controlling for pediatrician and practice
characteristics. RESULTS: Lack of sufficient personnel was significantly
associated with fewer care coordination activities: leading a multidisciplinary
team (odds ratio [OR], 0.53), developing care plans (OR, 0.51), and connecting
with support services (OR, 0.42). Lacking communication skills was significantly
associated with lower odds of development of care plans (OR, 0.56) and assistance
with support services (OR, 0.64). Lack of time was significantly associated with
lower odds of leading a multidisciplinary team (OR, 0.53). A pediatrician's
belief that the FCMH encourages the use of preventive services was significantly
associated with increased support services (OR, 2.06). CONCLUSIONS: Pediatricians
report a need for sufficient personnel and communication skills to provide care
coordination, a core component of the FCMH. Interventions to boost FCMH
implementation should focus on providing resources to develop these
characteristics.
PMID- 27507895
TI - A 3-Day-Old Girl Referred From Her Pediatrician for Oral Ulcerations.
AB - A 3-day-old girl was referred from her pediatrician for oral ulcerations. The
patient was otherwise well appearing and afebrile. Her prenatal and antenatal
courses were unremarkable, except for a failed routine hearing screen. The
patient's examination was notable for several yellowish ulcers on erythematous
bases located on her anterior tonsillar pillars. The patient also had a right
coloboma and a II/VI systolic ejection murmur. Laboratory analyses revealed a
traumatic lumbar puncture with 182 000 red blood cells and 808 white blood cells,
as well as a complete blood count that showed thrombocytopenia and leukocytosis.
During the patient's hospitalization, she developed a new facial rash. Her
physical examination findings, along with her diagnostic evaluation and hospital
course, ultimately led to 2 surprising diagnoses elaborated on in this case
discussion.
PMID- 27507896
TI - Reciprocal Regulation of 11beta-HSDs May Predict Steroid Sensitivity in Childhood
Nephrotic Syndrome.
AB - Childhood nephrotic syndrome, in which steroid-dependence occurs concurrently
with steroid-resistance, requires aggressive therapy to prevent relapse.
Predictive biomarkers that can be used to stratify treatment are urgently needed.
Here we report that reciprocal regulation of the glucocorticoid metabolizing
enzymes, 11beta-hydroxysteroid dehydrogenase types 1 and 2, is associated with
steroid-responsiveness and disease remission in childhood nephrotic syndrome,
potentially providing a marker to identify patients in which aggressive therapy
is required.
PMID- 27507897
TI - Urine 2-Hydroxyglutarate in Glioma.
PMID- 27507898
TI - In Reply.
PMID- 27507899
TI - Relieving dyspnoea by non-invasive ventilation decreases pain thresholds in
amyotrophic lateral sclerosis.
AB - BACKGROUND: Dyspnoea is a threatening sensation of respiratory discomfort that
presents many similarities with pain. Experimental dyspnoea in healthy subjects
induces analgesia. This 'dyspnoea-pain counter-irritation' could, in reverse,
imply that relieving dyspnoea in patients with chronic respiratory diseases would
lower their pain thresholds. METHODS: We first determined pressure pain
thresholds in 25 healthy volunteers (22-31 years; 13 men; handheld algometer),
during unloaded breathing (BASELINE) and during inspiratory threshold loading
(ITL). Two levels of loading were used, adjusted to induce dyspnoea self-rated at
60% or 80% of a 10 cm visual analogue scale (ITL6 and ITL8). 18 patients with
chronic respiratory failure due to amyotrophic lateral sclerosis (ALS) were then
studied during unassisted breathing and after 30 and 60 min of non-invasive
ventilation-NIV30 and NIV60-(same dyspnoea evaluation). RESULTS: In healthy
volunteers, pressure pain thresholds increased significantly in the deltoid
during ITL6 (p<0.05) and ITL8 (p<0.05) and in the trapezius during ITL8 (p<0.05),
validating the use of pressure pain thresholds to study dyspnoea-pain counter
irritation. In patients with ALS, the pressure pain thresholds measured in the
deltoid during unassisted breathing decreased by a median of 24.5%-33.0% of
baseline during NIV30 and NIV60 (p<0.05). CONCLUSION: Relieving dyspnoea by NIV
in patients with ALS having respiratory failure is associated with decreased
pressure pain thresholds. Clinical implications have yet to be determined, but
this observation suggests that patients with ALS could become more susceptible to
pain after the institution of NIV, hence the need for reinforced attention
towards potentially painful diagnostic and therapeutic interventions.
PMID- 27507900
TI - NIV for OHS without severe OSAS: is it worth it?
PMID- 27507901
TI - Design and methods of the Population Assessment of Tobacco and Health (PATH)
Study.
AB - BACKGROUND: This paper describes the methods and conceptual framework for Wave 1
of the Population Assessment of Tobacco and Health (PATH) Study data collection.
The National Institutes of Health, through the National Institute on Drug Abuse,
is partnering with the Food and Drug Administration's (FDA) Center for Tobacco
Products to conduct the PATH Study under a contract with Westat. METHODS: The
PATH Study is a nationally representative, longitudinal cohort study of 45 971
adults and youth in the USA, aged 12 years and older. Wave 1 was conducted from
12 September 2013 to 15 December 2014 using Audio Computer-Assisted Self
Interviewing to collect information on tobacco-use patterns, risk perceptions and
attitudes towards current and newly emerging tobacco products, tobacco
initiation, cessation, relapse behaviours and health outcomes. The PATH Study's
design allows for the longitudinal assessment of patterns of use of a spectrum of
tobacco products, including initiation, cessation, relapse and transitions
between products, as well as factors associated with use patterns. Additionally,
the PATH Study collects biospecimens from consenting adults aged 18 years and
older and measures biomarkers of exposure and potential harm related to tobacco
use. CONCLUSIONS: The cumulative, population-based data generated over time by
the PATH Study will contribute to the evidence base to inform FDA's regulatory
mission under the Family Smoking Prevention and Tobacco Control Act and efforts
to reduce the Nation's burden of tobacco-related death and disease.
PMID- 27507902
TI - The inside and outside: topological issues in plant cell wall biosynthesis and
the roles of nucleotide sugar transporters.
AB - The cell wall is a complex extracellular matrix composed primarily of
polysaccharides. Noncellulosic polysaccharides, glycoproteins and proteoglycans
are synthesized in the Golgi apparatus by glycosyltransferases (GTs), which use
nucleotide sugars as donors to glycosylate nascent glycan and glycoprotein
acceptors that are subsequently exported to the extracellular space. Many
nucleotide sugars are synthesized in the cytosol, leading to a topological issue
because the active sites of most GTs are located in the Golgi lumen. Nucleotide
sugar transporters (NSTs) overcome this problem by translocating nucleoside
diphosphate sugars from the cytosol into the lumen of the organelle. The
structures of the cell wall components synthesized in the Golgi are diverse and
complex; therefore, transporter activities are necessary so that the nucleotide
sugars can provide substrates for the GTs. In this review, we describe the
topology of reactions involved in polysaccharide biosynthesis in the Golgi and
focus on the roles of NSTs as well as their impacts on cell wall structure when
they are altered.
PMID- 27507903
TI - Full-spectrum (FUSE) versus standard forward-viewing colonoscopy in an organised
colorectal cancer screening programme.
AB - OBJECTIVE: Miss rate of polyps has been shown to be substantially lower with full
spectrum endoscopy (FUSE) compared with standard forward-viewing (SFV)
colonoscopy in a tandem study at per polyp analysis. However, there is
uncertainty on whether FUSE is also associated with a higher detection rate of
colorectal neoplasia, especially advanced lesions, in per patient analysis.
METHODS: Consecutive subjects undergoing colonoscopy following a positive faecal
immunochemical test (FIT) by experienced endoscopists and performed in the
context of a regional colorectal cancer population-screening programme were
randomised between colonoscopy with either FUSE or SFV colonoscopy in seven
Italian centres. Randomisation was stratified by gender, age group and screening
history. Primary outcomes included detection rates of advanced adenomas (A-ADR),
adenomas (ADR) and sessile-serrated polyps (SSPDR). RESULTS: Of 741 eligible
subjects, 658 were randomised to either FUSE (n=328) or SFV (n=330) colonoscopy
and included in the analysis. Overall, 293/658 and 143/658 subjects had at least
one adenoma (ADR 44.5%) and advanced adenoma (A-ADR 21.7%), respectively, while
SSP was the most advanced lesion in 18 cases (SSPDR 2.7%). ADR and A-ADR were
43.6% and 19.5% in the FUSE arm, and 45.5% and 23.9% in the SFV arm, with no
difference for both ADR (OR for FUSE: 0.96, 95% CI 0.81 to 1.14) and A-ADR (OR
for FUSE: 0.82, 95% CI 0.61 to 1.09). No difference in SSPDR or multiplicity was
detected between the two arms. In the per polyp analysis, the mean number of
adenomas and proximal adenomas per patient was 0.81+/-1.25 and 0.47+/-0.93 in the
FUSE arm, and 0.85+/-1.33 and 0.48+/-0.96 in the SFV colonoscopy arm (p=NS for
both comparisons). CONCLUSIONS: No statistically significant difference in ADR
and A-ADR between FUSE and SFV colonoscopy was detected in a per patient analysis
in FIT-positive patients. TRIAL REGISTRATION NUMBER: ISRCTN10357435.
PMID- 27507904
TI - Integrated genomic analysis of recurrence-associated small non-coding RNAs in
oesophageal cancer.
AB - OBJECTIVE: Oesophageal squamous cell carcinoma (ESCC) is a heterogeneous disease
with variable outcomes that are challenging to predict. A better understanding of
the biology of ESCC recurrence is needed to improve patient care. Our goal was to
identify small non-coding RNAs (sncRNAs) that could predict the likelihood of
recurrence after surgical resection and to uncover potential molecular mechanisms
that dictate clinical heterogeneity. DESIGN: We developed a robust prediction
model for recurrence based on the analysis of the expression profile data of
sncRNAs from 108 fresh frozen ESCC specimens as a discovery set and assessment of
the associations between sncRNAs and recurrence-free survival (RFS). We also
evaluated the mechanistic and therapeutic implications of sncRNA obtained through
integrated analysis from multiple datasets. RESULTS: We developed a risk
assessment score (RAS) for recurrence with three sncRNAs (microRNA (miR)-223, miR
1269a and nc886) whose expression was significantly associated with RFS in the
discovery cohort (n=108). RAS was validated in an independent cohort of 512
patients. In multivariable analysis, RAS was an independent predictor of
recurrence (HR, 2.27; 95% CI, 1.26 to 4.09; p=0.007). This signature implies the
expression of DeltaNp63 and multiple alterations of driver genes like PIK3CA. We
suggested therapeutic potentials of immune checkpoint inhibitors in low-risk
patients, and Polo-like kinase inhibitors, mammalian target of rapamycin (mTOR)
inhibitors, and histone deacetylase inhibitors in high-risk patients. CONCLUSION:
We developed an easy-to-use prognostic model with three sncRNAs as robust
prognostic markers for postoperative recurrence of ESCC. We anticipate that such
a stratified and systematic, tumour-specific biological approach will potentially
contribute to significant improvement in ESCC treatment.
PMID- 27507905
TI - A randomised comparison of two faecal immunochemical tests in population-based
colorectal cancer screening.
AB - OBJECTIVE: Colorectal cancer screening programmes are implemented worldwide; many
are based on faecal immunochemical testing (FIT). The aim of this study was to
evaluate two frequently used FITs on participation, usability, positivity rate
and diagnostic yield in population-based FIT screening. DESIGN: Comparison of two
FITs was performed in a fourth round population-based FIT-screening cohort.
Randomly selected individuals aged 50-74 were invited for FIT screening and were
randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood
(FOB)-Gold (Sentinel, Italy) test (March-December 2014). A cut-off of 10 ug
haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for
FOB-Gold) was used for both FITs. RESULTS: In total, 19 291 eligible invitees
were included (median age 61, IQR 57-67; 48% males): 9669 invitees received OC
Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96).
Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using
FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold
(p=0.002). There was no significant difference in diagnostic yield of advanced
neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive
predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same
positivity rate instead of cut-off, they yielded similar PPV and detection rates.
CONCLUSIONS: The OC-Sensor and FOB-Gold were equally acceptable to a screening
population. However, FOB-Gold was prone to more non-analysable tests. Comparison
between FIT brands is usually done at the same Hb stool concentration. Our
findings imply that for a fair comparison on diagnostic yield between FIT's
positivity rate rather than Hb concentration should be used. TRIAL REGISTRATION
NUMBER: NTR5385; Results.
PMID- 27507906
TI - Erratum: Are we meeting the standards set for endoscopy? Results of a large-scale
prospective survey of endoscopic retrograde cholangio-pancreatograph practice.
PMID- 27507908
TI - Efficacy of single serum cortisol reading obtained between 9 AM and 10 AM as an
index of adrenal function in children treated with glucocorticoids or synthetic
adrenocorticotropic hormone.
AB - To find a simple method to screen for iatrogenic childhood adrenal insufficiency,
we retrospectively examined the results of CRH stimulation tests performed 212
times on 111 subjects (68 males; age at commencement of initial treatment ranged
0.0-19.8 yr; median age, 5.8 yr). Before the commencement of this study, 97
subjects had been treated with glucocorticoids and 14 subjects with West syndrome
had been treated with synthetic adrenocorticotropic hormone. Duration of the
primary treatment ranged from 15 to 2150 days. CRH stimulation tests were
conducted between 09:00 AM and 10:00 AM and peak cortisol values less than 15
ug/dL were considered indicative of adrenal insufficiency. The receiver operating
characteristic curve showed that the optimal basal serum cortisol cut-off values
when screening for adrenal suppression ranged from 5.35 to 5.80 ug/dL depending
on the primary disease. All subjects having a serum cortisol value of less than
2.3 ug/dL had insufficient adrenal function while all subjects having greater
than 11 ug/dL had intact adrenal function. We concluded that single serum
cortisol values obtained between 09:00 AM and 10:00 AM had the potential to serve
as an index of adrenal function in children treated with glucocorticoids or
synthetic adrenocorticotropic hormone.
PMID- 27507907
TI - Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease:
Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis).
AB - PURPOSE: To determine if chronic graft-versus-host disease (cGVHD) after
allogeneic hematopoietic stem cell transplantation (HSCT) is associated with
stable or progressive dry eye disease and to determine the true incidence in
patients with no prior history of dry eye disease. METHODS: A nonconcurrent
cohort study at a single institution with 136 patients who had no previous
history of dry eye disease before HSCT. Survival analysis was used to estimate
dry eye disease incidence. The incidence rate was calculated using life tables as
the number of observed dry eye disease cases divided by the person-time at risk
accumulated by the cohort. Transition probabilities were calculated from time of
transplant to time of diagnosis, and then to last recorded visit. RESULTS:
Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the
population at risk developed dry eye disease during the first 10 months post
transplant. Time to develop dry eye disease was 2.5 months for mild dry eye
disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry
eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye
disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis.
CONCLUSIONS: Our findings suggest that dry eye disease associated with cGVHD is
an extremely frequent event and shows a wide spectrum of severity, with a mild
form presenting early and a moderate to severe form presenting later after HSCT.
These findings need to be studied further to elucidate if these are two different
pathophysiological entities or just different expressions of the same pathology.
PMID- 27507909
TI - Potential utility of cinacalcet as a treatment for CDC73-related primary
hyperparathyroidism: a case report.
AB - We report a Japanese pedigree with familial primary hyperparathyroidism due to a
CDC73 mutation. To our knowledge, this is the first report of cinacalcet as a
treatment for CDC73-related primary hyperparathyroidism. The proband had severe
psychomotor retardation and received laryngotracheal separation surgery. At 19 yr
of age, he developed acute pancreatitis. Hypercalcemia (12.2-13.8 mg/dL),
elevated levels of intact PTH (86-160 pg/mL), and a tumor detected upon neck
ultrasonography led to the diagnosis of primary hyperparathyroidism. Family
history and biochemical examinations revealed that three family members (the
proband's mother, elder brother, and maternal grandfather) had primary
hyperparathyroidism. We identified a novel heterozygous mutation, c.240delT,
p.Glu81Lysfs*28, in the CDC73 gene in three affected family members, excluding
the proband's elder brother who refused genetic testing. Parathyroidectomy for
the proband was considered as high-risk, because the tumor was located close to
the tracheostomy orifice. After receiving approval from the institutional review
board and obtaining the consent, we initiated cinacalcet treatment. At 22 yr of
age, treatment with 100 mg of cinacalcet maintained serum calcium levels below
11.0 mg/dL with no apparent side effects. Our report presents the potential
efficacy of cinacalcet as a treatment for CDC73-related primary
hyperparathyroidism, in particularly inoperative cases.
PMID- 27507910
TI - Chromosome 6q24 methylation defects are uncommon in childhood-onset non
autoimmune diabetes mellitus patients born appropriate- or large-for-gestational
age.
PMID- 27507911
TI - A Japanese familial case of hypochondroplasia with a novel mutation in FGFR3.
PMID- 27507912
TI - A Japanese familial case of Schmid metaphyseal chondrodysplasia with a novel
mutation in COL10A1.
PMID- 27507913
TI - A novel NR3C2 mutation in a Japanese patient with the renal form of
pseudohypoaldosteronism type 1.
PMID- 27507914
TI - A novel frameshift mutation in the TRPS1 gene caused Tricho-rhino-phalangeal
syndrome type I and III in a Japanese family.
PMID- 27507915
TI - Comparative Evaluation of the Remineralizing Effects and Surface Micro hardness
of Glass Ionomer Cements Containing Bioactive Glass (S53P4):An in vitro Study.
AB - Dental cements including the glass ionomer cement (GIC) have found widespread use
in restoring tooth structures. In this study, modifications of glass ionomer
cements (GICs) were made by adding bioactive glass (BAG) to GIC to obtain
bioactive restorative materials. This study used polarized light microscopy (PLM)
to examine the remineralization effects of the study materials on dentin. It also
evaluated the Vickers microhardness of the experimental materials. Experimental
glass ionomer cement (GIC)-BAG materials were made by mixing 10 wt% of BAG
particles with conventional cure and resin-modified GIC powders. Class V
restorations were made in 80 extracted mandibular teeth which included 4 groups
of 20 teeth each. 100 |jm sections of the teeth were examined under polarized
light microscope after undergoing pH cycling. Materials were also processed into
80 cylindrical specimens and immersed in water for 7 and 30 days before
mechanical tests. Resin-modified GIC containing BAG showed a thick uniform layer
of mineralization on the restoration-dentin interface. The conventional cure GIC
based materials had higher surface microhardness than the resin-modified
materials. SIGNIFICANCE: The addition of BAG to GIC compromises the mechanical
properties of the materials to some extent. Thus, their clinical use ought to be
restricted to applications where their bioactivity can be beneficial, such as
root surface fillings and liners in dentistry.
PMID- 27507916
TI - Interrelationship among Dental, Skeletal and Chronological Ages in Urban and
Rural Female Children.
AB - AIM: This study was an attempt, to determine chronological age, dental age and
skeletal age, and to establish interrelationship, amongst the dental, skeletal
and chronological ages and their differences if any between rural and urban
female children. The study included 80 girls aged 8 to 14 years from rural and
urban areas. MATERIAL AND METHODS: The subjects were divided into 4 Groups: Group
I, II, III, and IV. Group I and II comprising of rural female subjects, wherein
Group I comprised of 8 to 11 years and Group II comprised of 11 to 14 years old
females. Group III and IV comprising of urban females wherein Group III included
8 to 11 years and Group IV comprised of 11 to 14 years old females.
Orthopantomograms and hand and wrist radiographs were taken. The calcification
status of permanent teeth was evaluated from orthopantomograms, and dental age
was calculated according to Demirjian's method. The stages of ossification of
various carpal bones were evaluated from the hand-wrist radiograph using
radiographic atlas of Greulich and Pyle and skeletal age was calculated. The
chronological age was recorded from the actual date of birth. RESULTS: Data
collected was statistically analyzed. CONCLUSION: Highly significant correlation
was observed between dental and skeletal age (r=0.752, p-value < 0.01) in total
sample. Strong correlation of chronological age with dental and skeletal age was
also observed (r=0.650, r = 0.620, respectively). Out of all three correlations,
dental age and skeletal age had the maximum correlation in total sample. While
comparing rural and urban sample as regard to ages or correlations no significant
difference was found (p-value < 0.01).
PMID- 27507917
TI - Aloe-Vera: A Nature's Gift to Children.
AB - (1)Aloe-Barbadensis Mill (Liliaceae) is used in the traditional medicine of
Mexico and other countries for anti-inflammatory and cosmetic purposes (Diez
Martinez 1981, Grindlay and Reynolds 1986). Two components are obtained from the
fresh leaves of Aloe-Barbadensis, a bitter yellow juice (exudate), which drains
from the transversally cut leaves used as a laxative (Ishii et al 1990) and a
mucilaginous gel from leaf parenchyma, which has been used as a remedy for a
variety of pathological states such as arthritis, gout, acne, dermatitis, burns
and peptic ulcers induced by epithelial alterations (Cap-passo and Ganginella
1997, Reynolds and Dweek 1999). The aim of this study is to evaluate efficacy of
Aloe-Vera gel as a healing agent in an endodontic procedure called pulpotomy.
Fifteen primary molars were treated for pulpotomy using 'Aloe-Vera gel'. Patients
were recalled after 1 month to check for any clinical symptoms. None of the
patients reported with clinical symptoms of pain, mobility, abscess and
histopathological evaluation done following extraction after 2 months showed
positive signs of healing.
PMID- 27507918
TI - Antibacterial Properties of Fluoride Releasing Glass lonomer Cements (GICs) and
Pit and Fissure Sealants on Streptococcus Mutans.
AB - TITLE: Antibacterial properties of fluoride releasing glass Ionomer cements
(GICs) and pit and fissure sealants on Streptococcus mutans. BACKGROUND: Occlusal
pit and fissures are the most susceptible sites for dental caries. The clinical
effectiveness of GICs and fissure sealants in preventing caries is well
documented, but there is some concern about bacteria left beneath sealants.
OBJECTIVE: (1) Study the antibacterial activity of GICs and pit and fissure
sealants. (2) Compare between these materials. METHODOLOGY: GICs (Fuji IX GP and
Ketac molar) and pit and fissure sealants (Teethmate-F1 and Helioseal-F ). The
strains was grown in the Brain Heart Infusion broth and was incubated
anaerobically for 18 hours at 37 degrees C and subcultured in MSB agar.Four wells
measuring 5 mm diameter was prepared on each agar plate and the prepared
materials was placed and further incubated anaerobically for 48 hours at 37
degrees C. The zone of inhibition was measured. RESULTS: All the materials tested
showed antibacterial properties to varying levels except; among pit and fissure
sealants it is Teethmate-F which showed more antibacterial property. CONCLUSION:
Teethmate-F1 sealant showed more antibacterial property compared to Fuji IX and
Ketac molar. Helioseal-F did not show any antibacterial property.
PMID- 27507919
TI - Fabrication of an Ocular Prosthesis for a Pediatric Retinoblastoma Patient by a
Simplified Technique.
AB - Retinoblastoma is one of the more highly invasive and common intraocular
malignancies of childhood. Treatment in most of the cases consists of enucleation
followed by placement of orbital implants. Prosthetic rehabilitation is
especially challenging in younger and precooperative pediatric patients. The
following case report describes the rehabilitation of a 4-year-old child with
retinoblastoma, with an ocular prosthesis fabricated by a simplified technique.
PMID- 27507920
TI - Bilateral Transverse Facial Cleft as an Isolated and Asyndromic Deformity.
AB - Congenital macrostomia or transverse facial cleft is a rare congenital
craniofacial anomaly, which affects the esthetics and functions of oral cavity.
It is usually associated with deformities of other structures developed from the
first and second branchial arches. Bilateral transverse cleft, occurring alone is
uncommon. Since the deformity is rare, its treatment has not been commonly
described in the literature. We report a case of congenital bilateral macrostomia
as an isolated, asyndromic deformity to add one more case in the literature and
surgical technique has been discussed here.
PMID- 27507921
TI - Radix Entomolaris: A Clinical Challenge.
AB - A major anatomical variant of the two-rooted mandibular first molar is a tooth
with an additional distolingual third root: The radix entomolaris (RE). It is
essential to anticipate and find all roots and canals during root canal
treatment. Proper angulations and interpretation of radiographs help to identify
pulp chamber and root anatomy. If present, an awareness and understanding of this
unusual root and its root canal morphology can contribute to the successful
outcome of root canal treatment.
PMID- 27507922
TI - Management of Developing Anterior Malocclusion due to SupernumeraryTooth with
Preventive and Intercep-tive Approach: A 11/2 Year Case Study.
AB - Variety of clinical complications occurs due to the presence of supernumerary
teeth, especially mesiodens. It may result in impaction of one or both central
incisors which in turn may lead to a variety of malocclusions. Timely
intervention not only prevents malocclusion but also the time taken for
corrective orthodontics. A complete case report of developing mesiodens' tooth
germ resulting in malocclusion including treatment in 11/2 year period is
presented.
PMID- 27507923
TI - Maxillary Growth Encircling the Central Incisor Crown.
AB - During osteogenesis, mesenchymal tissues function to form fibrous matrix which
changes into bone by ossification. In rare instances, fibrous matrix persists in
which foci of immature bone is evident resulting in progressive enlargement. Such
conditions are commonly benign in nature but few are anatomically benign and
clinically destructive. Though recurrence and residual defects following surgical
treatment are the challenging complications, fatal consequences are infrequent.
We report a juvenile case of ossifying fibroma with an aim to highlight its
clinical course and salient criteria to differentiate this entity from the common
variants.
PMID- 27507924
TI - Complex Composite Odontoma.
AB - Odontomas are hamartomas composed of various dental tissues, i.e. enamel, dentin,
cementum and sometimes pulp. They are slow-growing, benign tumors showing
nonaggressive behavior. Most of the odontomes are asymptomatic with unknown
etiology, although occasional signs and symptoms related to their presence do
occur. Presented here is the case report of 10-year-old girl with impacted left
central incisor.
PMID- 27507925
TI - Conservative Management of Dens Evaginatus: Report of Two Unusual Cases.
AB - Dens evaginatus (DE) is a rare developmental anomaly characterized by presence of
an extra cusp arising from occlusal or lingual surfaces. Isolated occurrence or
concomitant presence of DE with other dental anomalies has been reported. DE
commonly affects permanent teeth and is rarely seen in primary dentition.
Treatment may be conservative or radical. This article presents two unusual cases
of concomitant occurrence of a supernumerary tooth and DE affecting maxillary
deciduous lateral incisor and conservative management of DE occurring
concurrently with a possible Oehler's type I invagination in maxillary permanent
lateral incisor.
PMID- 27507926
TI - Editorial.
PMID- 27507927
TI - Nurse students' experiences with clinical placement in outpatient unit - a
qualitative study.
AB - BACKGROUND: The recent reforms in the health care sector have changed the
requirements for professional nursing competence in the clinical field. The
reforms have also required nursing education to consider different areas for
clinical placements for their students, and outpatient units in hospitals have
been increasingly formalized as clinical learning environments. The complex
technologies in some of these units represent a challenge for students who have
limited existing knowledge or experience. More focus on outpatient care has also
led to fewer opportunities for studying the continuity of a patient's life
situation. In order to meet these challenges, structured learning activities with
special forms were developed by nursing educators and nurses at outpatient units.
The aim of this study was to explore students' experiences of using structured
learning activities as unit-specific learning outcomes and targeted reflection
during clinical placements in an outpatient unit. METHODS: Two focus group
interviews were conducted with a total of seven nursing students who had
experienced structured learning activities during clinical placements in an
outpatient unit. Data were analyzed by means of content analyses. RESULTS: This
study shows that preparedness and guidance during placement were imperative for
making the week in the outpatient unit meaningful. 'Being prepared', which was
one of the categories, incorporated the subcategories 'being able to understand
what to do', 'being at the right place at the right time' and 'being alert for
new experiences'. The category 'being guided' which incorporated the
subcategories 'from uncertainty to more confidence', 'from observer to seeking
knowledge' and 'from focusing on technology to seeing the person' showed that the
forms guided the students through the placement in the outpatient unit.
DISCUSSION: Students take a more active approach to seeking knowledge when given
structured learing activities during clinical placement in outpatient unit.
CONCLUSIONS: This study shows that use of outpatient units for clinical placement
in nursing studies has several challenges but also the potential for creating
positive experiences for the students.
PMID- 27507928
TI - Current tobacco use and its associated factors among adults in a country with
comprehensive ban on tobacco: findings from the nationally representative STEPS
survey, Bhutan, 2014.
AB - BACKGROUND: Despite a comprehensive ban on cultivation, manufacture,
distribution, and sale of tobacco products since 2004, two nationwide surveys
conducted in 2012 and 2013 reported high tobacco use in Bhutan. National Health
Survey 2012 reported that 4 % of the population aged 15-75 years used smoked
tobacco and about 48 % used smokeless tobacco. Similarly, Global Youth Tobacco
Survey (GYTS) of Bhutan reported tobacco use prevalence of 30.3 % in 2013.
However, factors associated with this high tobacco use were not systematically
studied. Hence, we assessed the prevalence of tobacco use and its associated
sociodemographic, behavioral, and environmental factors. METHODS: This cross
sectional analytical study used secondary data collected in a nationally
representative Non-communicable Disease Risk Factors Surveillance STEPS Survey
2014 conducted among Bhutanese adults (18-69 years). The survey included a total
of 2820 adults; selected using multistage stratified cluster sampling. Weighted
analysis was done to calculate the prevalence of tobacco use. Unadjusted and
adjusted prevalence ratios were calculated using log binomial regression.
RESULTS: The prevalence of current overall tobacco use was 24.8 % (95 % CI: 21.4
28.3) and that of smoked, smokeless, and dual forms (smoked and smokeless forms)
were 7.4 % (95 % CI: 5.8-9.0), 19.7 % (95 % CI: 16.5-22.9), and 2.3 % (95 % CI:
1.8-2.9), respectively. Significantly higher prevalence of tobacco use in all
forms was found among males, younger age groups, and alcohol users. The
prevalence of smoked form was higher in urban areas compared to rural areas (11 %
vs 6 %; aPR 1.8, 95 % CI: 1.5-2.0). Among individuals who reported having a non
communicable disease, the prevalence of smoked tobacco use was significantly
lower than those who did not have disease (3.5 % vs. 8.3 %; aPR 0.5, 95 % CI: 0.3
0.9). Exposure to health warnings was protective for current tobacco use and
smokeless tobacco use, while exposure to tobacco warnings through the media was
helpful among smokers and overall tobacco users. CONCLUSIONS: Despite a
comprehensive ban on tobacco, tobacco use was high in Bhutan, especially the
smokeless form. Males, younger age groups, and alcohol users should be targeted
with behavioral interventions along the stricter implementation of tobacco
control measures.
PMID- 27507930
TI - Effects of varenicline on sympatho-vagal balance and cue reactivity during
smoking withdrawal: a randomised placebo-controlled trial.
AB - BACKGROUND: Varenicline is an effective smoking cessation medication. Some
concern has been raised that its use may precipitate adverse cardiovascular
events although no patho-physiological mechanism potentially underlying such an
effect has been reported. The aim of this study was to test the hypothesis that
varenicline impacts on sympatho-vagal balance during smoking withdrawal. METHODS:
In this randomised, placebo-controlled trial, muscle sympathetic nerve activity
(MSNA), baroreflex sensitivity (BRS), heart rate, and blood pressure were
assessed in 17 smokers four weeks before a quit attempt (baseline) and again on
the third day of that quit attempt (acute smoking withdrawal). RESULTS: Regarding
the primary endpoint of our study, we did not find a significant effect of
varenicline compared to placebo on changes in MSNA burst incidence between
baseline and acute smoking withdrawal (-3.0 +/- 3.3 vs.-3.9 +/- 5.0 bursts/100
heart beats; p = 0.308). However, heart rate and systolic blood pressure
significantly decreased in the placebo group only, while no significant changes
in these parameters were observed in the varenicline group. Exposure to smoking
cues during acute withdrawal lead to a significant increase of heart rate in the
placebo group, while heart rate decreased in the varenicline group, and the
difference in these changes was significant between groups (+2.7 +/- 1.0 vs.-1.8
+/- 0.5 1/min; p = 0.002). In all 17 participants combined, a significant
increase in heart rate during smoking cue exposure was detected in subjects who
relapsed in the course of six weeks after the quit date compared to those who
stayed abstinent (+2.5 +/- 1.2 vs.-1.1 +/- 0.7; p = 0.018). Six-week abstinence
rates were higher in the varenicline group compared to placebo (88 vs. 22 % p =
0.015). CONCLUSION: We did not find evidence of adverse effects of varenicline on
sympatho-vagal balance. Varenicline probably blunts the heart rate response to
smoking cues, which may be linked to improved cessation outcome.
PMID- 27507929
TI - Estrogen-related receptor beta (ERRbeta) - renaissance receptor or receptor
renaissance?
AB - Estrogen-related receptors (ERRs) are founding members of the orphan nuclear
receptor (ONR) subgroup of the nuclear receptor superfamily. Twenty-seven years
of study have yet to identify cognate ligands for the ERRs, though they have
firmly placed ERRalpha and ERRgamma at the intersection of cellular metabolism
and oncogenesis. The pace of discovery for novel functions of ERRbeta, however,
has until recently been somewhat slower than that of its family members. ERRbeta
has also been largely ignored in summaries and perspectives of the ONR
literature. Here, we provide an overview of established and emerging knowledge of
ERRbeta in mouse, man, and other species, highlighting unique aspects of ERRbeta
biology that set it apart from the other two estrogen-related receptors, with a
focus on the impact of alternative splicing on the structure and function of this
receptor.
PMID- 27507931
TI - Entire Sound Representations Are Time-Compressed in Sensory Memory: Evidence from
MMN.
AB - In order to examine the encoding of partial silence included in a sound stimulus
in neural representation, time flow of the sound representations was investigated
using mismatch negativity (MMN), an ERP component that reflects neural
representation in auditory sensory memory. Previous work suggested that time flow
of auditory stimuli is compressed in neural representations. The stimuli used
were a full-stimulus of 170 ms duration, an early-gap stimulus with silence for a
20-50 ms segment (i.e., an omitted segment), and a late-gap stimulus with an
omitted segment of 110-140 ms. Peak MMNm latencies from oddball sequences of
these stimuli, with a 500 ms SOA, did not reflect time point of the physical gap,
suggesting that temporal information can be compressed in sensory memory.
However, it was not clear whether the whole stimulus duration or only the omitted
segment duration is compressed. Thus, stimuli were used in which the gap was
replaced by a tone segment with a 1/4 sound pressure level (filled), as well as
the gap stimuli. Combinations of full-stimuli and one of four gapped or filled
stimuli (i.e., early gap, late gap, early filled, and late filled) were presented
in an oddball sequence (85 vs. 15%). If compression occurs only for the gap
duration, MMN latency for filled stimuli should show a different pattern from
those for gap stimuli. MMN latencies for the filled conditions showed the same
pattern as those for the gap conditions, indicating that the whole stimulus
duration rather than only gap duration is compressed in sensory memory neural
representation. These results suggest that temporal aspects of silence are
encoded in the same manner as physical sound.
PMID- 27507932
TI - Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced
Locomotor Abnormalities in Rats.
AB - Vestibular damage can induce locomotor abnormalities in both animals and humans.
Rodents with bilateral vestibular loss showed vestibular deficits syndrome such
as circling, opisthotonus as well as locomotor and exploratory hyperactivity.
Previous studies have investigated the changes in the dopamine system after
vestibular loss, but the results are inconsistent and inconclusive. Numerous
evidences indicate that the orexin system is implicated in central motor control.
We hypothesized that orexin may be potentially involved in vestibular loss
induced motor disorders. In this study, we examined the effects of arsanilate- or
3,3'-iminodipropionitrile (IDPN)-induced vestibular lesion (AVL or IVL) on the
orexin-A (OXA) labeling in rat hypothalamus using immunohistochemistry. The
vestibular lesion-induced locomotor abnormalities were recorded and verified
using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.). The effects
of the orexin receptor type 1 antagonist SB334867 (16 MUg, i.c.v.) on these
behavior responses were also investigated. At 72 h post-AVL and IVL, animals
exhibited vestibular deficit syndrome and locomotor hyperactivity in the home
cages. These responses were significantly alleviated by JNJ7777120 which also
eliminated AVL-induced increases in exploratory behavior in an open field. The
numbers of OXA-labeled neurons in the hypothalamus were significantly increased
in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48, and 72 h
post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and
locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory
behavior in the AVL animals. These results suggested that the alteration of OXA
expression might contribute to locomotor abnormalities after acute vestibular
lesion. The orexin receptors might be the potential therapeutic targets for
vestibular disorders.
PMID- 27507933
TI - Analysis of Amyloid Precursor Protein Function in Drosophila melanogaster.
AB - The Amyloid precursor protein (APP) has mainly been investigated in connection
with its role in Alzheimer's Disease (AD) due to its cleavage resulting in the
production of the Abeta peptides that accumulate in the plaques characteristic
for this disease. However, APP is an evolutionary conserved protein that is not
only found in humans but also in many other species, including Drosophila,
suggesting an important physiological function. Besides Abeta, several other
fragments are produced by the cleavage of APP; large secreted fragments derived
from the N-terminus and a small intracellular C-terminal fragment. Although these
fragments have received much less attention than Abeta, a picture about their
function is finally emerging. In contrast to mammals, which express three APP
family members, Drosophila expresses only one APP protein called APP-like or
APPL. Therefore APPL functions can be studied in flies without the complication
that other APP family members may have redundant functions. Flies lacking APPL
are viable but show defects in neuronal outgrowth in the central and peripheral
nervous system (PNS) in addition to synaptic changes. Furthermore, APPL has been
connected with axonal transport functions. In the adult nervous system, APPL, and
more specifically its secreted fragments, can protect neurons from degeneration.
APPL cleavage also prevents glial death. Lastly, APPL was found to be involved in
behavioral deficits and in regulating sleep/activity patterns. This review, will
describe the role of APPL in neuronal development and maintenance and briefly
touch on its emerging function in circadian rhythms while an accompanying review
will focus on its role in learning and memory formation.
PMID- 27507934
TI - Neuronal Actin Dynamics, Spine Density and Neuronal Dendritic Complexity Are
Regulated by CAP2.
AB - Actin remodeling is crucial for dendritic spine development, morphology and
density. CAP2 is a regulator of actin dynamics through sequestering G-actin and
severing F-actin. In a mouse model, ablation of CAP2 leads to cardiovascular
defects and delayed wound healing. This report investigates the role of CAP2 in
the brain using Cap2(gt/gt) mice. Dendritic complexity, the number and morphology
of dendritic spines were altered in Cap2(gt/gt) with increased number of
excitatory synapses. This was accompanied by increased F-actin content and F
actin accumulation in cultured Cap2(gt/gt) neurons. Moreover, reduced surface
GluA1 was observed in mutant neurons under basal condition and after induction of
chemical LTP. Additionally, we show an interaction between CAP2 and n-cofilin,
presumably mediated through the C-terminal domain of CAP2 and dependent on
cofilin Ser3 phosphorylation. In vivo, the consequences of this interaction were
altered phosphorylated cofilin levels and formation of cofilin aggregates in the
neurons. Thus, our studies identify a novel role of CAP2 in neuronal development
and neuronal actin dynamics.
PMID- 27507935
TI - Sustained Exocytosis after Action Potential-Like Stimulation at Low Frequencies
in Mouse Chromaffin Cells Depends on a Dynamin-Dependent Fast Endocytotic
Process.
AB - Under basal conditions the action potential firing rate of adrenal chromaffin
cells is lower than 0.5 Hz. The maintenance of the secretory response at such
frequencies requires a continuous replenishment of releasable vesicles. However,
the mechanism that allows such vesicle replenishment remains unclear. Here, using
membrane capacitance measurements on mouse chromaffin cells, we studied the
mechanism of replenishment of a group of vesicles released by a single action
potential-like stimulus (APls). The exocytosis triggered by APls (ETAP)
represents a fraction (40%) of the immediately releasable pool, a group of
vesicles highly coupled to voltage dependent calcium channels. ETAP was
replenished with a time constant of 0.73 +/- 0.11 s, fast enough to maintain
synchronous exocytosis at 0.2-0.5 Hz stimulation. Regarding the mechanism
involved in rapid ETAP replenishment, we found that it depends on the ready
releasable pool; indeed depletion of this vesicle pool significantly delays ETAP
replenishment. On the other hand, ETAP replenishment also correlates with a
dynamin-dependent fast endocytosis process (tau = 0.53 +/- 0.01 s). In this
regard, disruption of dynamin function markedly inhibits the fast endocytosis and
delays ETAP replenishment, but also significantly decreases the synchronous
exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5
Hz). Considering these findings, we propose a model in where both the transfer of
vesicles from ready releasable pool and fast endocytosis allow rapid ETAP
replenishment during low stimulation frequencies.
PMID- 27507936
TI - Distinct Roles of SOM and VIP Interneurons during Cortical Up States.
AB - During cortical network activity, recurrent synaptic excitation among pyramidal
neurons is approximately balanced by synaptic inhibition, which is provided by a
vast diversity of inhibitory interneurons. The relative contributions of
different interneuron subtypes to inhibitory tone during cortical network
activity is not well-understood. We previously showed that many of the major
interneuron subtypes in mouse barrel cortex are highly active during Up states
(Neske et al., 2015); while fast-spiking (FS), parvalbumin (PV)-positive cells
were the most active interneuron subtype, many non-fast-spiking (NFS), PV
negative interneurons were as active or more active than neighboring pyramidal
cells. This suggests that the NFS cells could play a role in maintaining or
modulating Up states. Here, using optogenetic techniques, we further dissected
the functional roles during Up states of two major NFS, PV-negative interneuron
subtypes: somatostatin (SOM)-positive cells and vasoactive intestinal peptide
(VIP)-positive cells. We found that while pyramidal cell excitability during Up
states significantly increased when SOM cells were optogenetically silenced, VIP
cells did not influence pyramidal cell excitability either upon optogenetic
silencing or activation. VIP cells failed to contribute to Up states despite
their ability to inhibit SOM cells strongly. We suggest that the contribution of
VIP cells to the excitability of pyramidal cells may vary with cortical state.
PMID- 27507937
TI - Spatiotemporal Features of Retinal Waves Instruct the Wiring of the Visual
Circuitry.
AB - Coordinated spontaneous activity is present in different sensory systems during
early stages of development. This activity is thought to play a critical role in
the development of sensory representations before the maturation of sensory
experience. In the visual system, the mechanisms by which spatiotemporal
properties of retinal spontaneous activity, called retinal waves, drive
developmental events has been well studied. Recent advancements in
pharmacological, genetic, and optogenetic manipulations have provided further
understanding of the contribution of specific spatiotemporal properties of
retinal waves to eye-specific segregation and retinotopic refinement of
retinofugal projections. Here we review some of the recent progress in
understanding the role of retinal waves in the early stages of visual system
development, prior to the maturation of vision.
PMID- 27507938
TI - The Pointing Errors in Optic Ataxia Reveal the Role of "Peripheral Magnification"
of the PPC.
AB - Interaction with visual objects in the environment requires an accurate
correspondence between visual space and its internal representation within the
brain. Many clinical conditions involve some impairment in visuo-motor control
and the errors created by the lesion of a specific brain region are neither
random nor uninformative. Modern approaches to studying the neuropsychology of
action require powerful data-driven analyses and error modeling in order to
understand the function of the lesioned areas. In the present paper we carried
out mixed-effect analyses of the pointing errors of seven optic ataxia patients
and seven control subjects. We found that a small parameter set is sufficient to
explain the pointing errors produced by unilateral optic ataxia patients. In
particular, the extremely stereotypical errors made when pointing toward the
contralesional visual field can be fitted by mathematical models similar to those
used to model central magnification in cortical or sub-cortical structure(s). Our
interpretation is that visual areas that contain this footprint of central
magnification guide pointing movements when the posterior parietal cortex (PPC)
is damaged and that the functional role of the PPC is to actively compensate for
the under-representation of peripheral vision that accompanies central
magnification. Optic ataxia misreaching reveals what would be hand movement
accuracy and precision if the human motor system did not include elaborated
corrective processes for reaching and grasping to non-foveated targets.
PMID- 27507939
TI - Increased Functional Activation of Limbic Brain Regions during Negative Emotional
Processing in Migraine.
AB - Pain is both an unpleasant sensory and emotional experience. This is highly
relevant in migraine where cortical hyperexcitability in response to sensory
stimuli (including pain, light, and sound) has been extensively reported.
However, migraine may feature a more general enhanced response to aversive
stimuli rather than being sensory-specific. To this end we used functional
magnetic resonance imaging to assess neural activation in migraineurs interictaly
in response to emotional visual stimuli from the International Affective Picture
System. Migraineurs, compared to healthy controls, demonstrated increased neural
activity in response to negative emotional stimuli. Most notably in regions
overlapping in their involvement in both nociceptive and emotional processing
including the posterior cingulate, caudate, amygdala, and thalamus (cluster
corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no
and minimal differences in response to positive and neutral emotional stimuli,
respectively. These findings support the notion that migraine may feature more
generalized altered cerebral processing of aversive/negative stimuli, rather than
exclusively to sensory stimuli. A generalized hypersensitivity to aversive
stimuli may be an inherent feature of migraine, or a consequential alteration
developed over the duration of the disease. This proposed cortical-limbic
hypersensitivity may form an important part of the migraine pathophysiology,
including psychological comorbidity, and may represent an innate sensitivity to
aversive stimuli that underpins attack triggers, attack persistence and
(potentially) gradual headache chronification.
PMID- 27507941
TI - Neural Correlates of Fear of Movement in Patients with Chronic Low Back Pain vs.
Pain-Free Individuals.
AB - Fear of movement (FOM) can be acquired by a direct aversive experience such as
pain or by social learning through observation and instruction. Excessive FOM
results in heightened disability and is an obstacle for recovery from acute,
subacute, and chronic low back pain (cLBP). FOM has further been identified as a
significant explanatory factor in the Fear Avoidance (FA) model of cLBP that
describes how individuals experiencing acute back pain may become trapped into a
vicious circle of chronic disability and suffering. Despite a wealth of evidence
emphasizing the importance of FOM in cLBP, to date, no related neural correlates
in patients were found and this therefore has initiated a debate about the
precise contribution of fear in the FA model. In the current fMRI study, we
applied a novel approach encompassing: (1) video clips of potentially harmful
activities for the back as FOM inducing stimuli; and (2) the assessment of FOM in
both, cLBP patients (N = 20) and age- and gender-matched pain-free subjects (N =
20). Derived from the FA model, we hypothesized that FOM differentially affects
brain regions involved in fear processing in patients with cLBP compared to pain
free individuals due to the recurrent pain and subsequent avoidance behavior. The
results of the whole brain voxel-wise regression analysis revealed that: (1) FOM
positively correlated with brain activity in fear-related brain regions such as
the amygdala and the insula; and (2) differential effects of FOM between patients
with cLBP and pain-free subjects were found in the extended amygdala and in its
connectivity to the anterior insula. Current findings support the FOM component
of the FA model in cLBP.
PMID- 27507940
TI - A Direct Cortico-Nigral Pathway as Revealed by Constrained Spherical
Deconvolution Tractography in Humans.
AB - Substantia nigra is an important neuronal structure, located in the ventral
midbrain, that exerts a regulatory function within the basal ganglia circuitry
through the nigro-striatal pathway. Although its subcortical connections are
relatively well-known in human brain, little is known about its cortical
connections. The existence of a direct cortico-nigral pathway has been
demonstrated in rodents and primates but only hypothesized in humans. In this
study, we aimed at evaluating cortical connections of substantia nigra in vivo in
human brain by using probabilistic constrained spherical deconvolution (CSD)
tractography on magnetic resonance diffusion weighted imaging data. We found that
substantia nigra is connected with cerebral cortex as a whole, with the most
representative connections involving prefrontal cortex, precentral and
postcentral gyri and superior parietal lobule. These results may be relevant for
the comprehension of the pathophysiology of several neurological disorders
involving substantia nigra, such as parkinson's disease, schizophrenia, and
pathological addictions.
PMID- 27507942
TI - Visualizing Presynaptic Calcium Dynamics and Vesicle Fusion with a Single
Genetically Encoded Reporter at Individual Synapses.
AB - Synaptic transmission depends on the influx of calcium into the presynaptic
compartment, which drives neurotransmitter release. Genetically encoded reporters
are widely used tools to understand these processes, particularly pHluorin-based
reporters that report vesicle exocytosis and endocytosis through pH dependent
changes in fluorescence, and genetically encoded calcium indicators (GECIs) that
exhibit changes in fluorescence upon binding to calcium. The recent expansion of
the color palette of available indicators has made it possible to image multiple
probes simultaneously within a cell. We have constructed a single molecule
reporter capable of concurrent imaging of both presynaptic calcium influx and
exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin
containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to
the fixed stoichiometry of the two probes, the ratio of the two responses can
also be measured, providing an all optical correlate of the calcium dependence of
release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of
hippocampal synapses in vitro, exploring the effects of different stimulus
strengths and frequencies as well as variations in external calcium
concentrations. By combining live sypHy-RGECO imaging with post hoc fixation and
immunofluorescence, we have also investigated correlations between structural and
functional properties of synapses.
PMID- 27507943
TI - Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is
Associated with Increased Oxidative Stress.
AB - Age-associated declines in protein homeostasis mechanisms ("proteostasis") are
thought to contribute to age-related neurodegenerative disorders. The increased
oxidative stress which occurs with aging can activate a key proteostatic process,
chaperone-mediated autophagy. This study investigated age-related alteration in
cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8),
a molecular chaperone involved in proteostatic mechanisms including chaperone
mediated autophagy, and its associations with indicators of oxidative stress (8
hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant
capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and
total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging
from 20 to 75 years of age. Age was negatively associated with HSPA8 (rho =
0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a
positive association between age and 8-OHdG (rho = 0.61; p = 0.0001). HSPA8 was
moderately negatively associated with 8-OHdG (rho = -0.58; p = 0.0004). Age and
HSPA8 were weakly associated with 8-isoprostane and TAC (range of rho values:
0.15 to 0.16). Our findings in this exploratory study suggest that during healthy
aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative
stress. Our results also suggest that 8-OHdG may be more sensitive than 8
isoprostane for measuring oxidative stress in CSF. Further studies are indicated
to determine if our findings can be replicated with a larger cohort, and if the
age-related decrease in HSPA8 in CSF is reflected by a similar change in the
brain.
PMID- 27507944
TI - Mood Influences the Concordance of Subjective and Objective Measures of Sleep
Duration in Older Adults.
AB - OBJECTIVE/BACKGROUND: Sleep plays a central role in maintaining health and
cognition. In most epidemiologic studies, sleep is evaluated by self-report
questionnaires but several reports suggest that these evaluations might be less
accurate than objective measures such as polysomnography or actigraphy.
Determinants of the discrepancy between objective and subjective measures remain
to be investigated. The aim of this pilot-study was to examine the role of mood
states in determining the discrepancy observed between objective and subjective
measures of sleep duration in older adults. PATIENTS/METHODS: Objective sleep
quantity and quality were recorded by actigraphy in a sample of 45 elderly
subjects over at least three consecutive nights. Subjective sleep duration and
supplementary data, such as mood status and memory, were evaluated using
ecological momentary assessment (EMA). RESULTS: A significant discrepancy was
observed between EMA and actigraphic measures of sleep duration (p < 0.001). The
magnitude of this difference was explained by the patient's mood status (p =
0.020). No association was found between the magnitude of this discrepancy and
age, sex, sleep quality or memory performance. CONCLUSION: The discrepancy
classically observed between objective and subjective measures of sleep duration
can be explained by mood status at the time of awakening. These results have
potential implications for epidemiologic and clinical studies examining sleep as
a risk factor for morbidity or mortality.
PMID- 27507945
TI - Cannabinoids As Potential Treatment for Chemotherapy-Induced Nausea and Vomiting.
AB - Despite the advent of classic anti-emetics, chemotherapy-induced nausea is still
problematic, with vomiting being somewhat better managed in the clinic. If post
treatment nausea and vomiting are not properly controlled, anticipatory nausea-a
conditioned response to the contextual cues associated with illness-inducing
chemotherapy-can develop. Once it develops, anticipatory nausea is refractive to
current anti-emetics, highlighting the need for alternative treatment options.
One of the first documented medicinal uses of Delta(9)-tetrahydrocannabinol
(Delta(9)-THC) was for the treatment of chemotherapy-induced nausea and vomiting
(CINV), and recent evidence is accumulating to suggest a role for the
endocannabinoid system in modulating CINV. Here, we review studies assessing the
therapeutic potential of cannabinoids and manipulations of the endocannabinoid
system in human patients and pre-clinical animal models of nausea and vomiting.
PMID- 27507946
TI - Relationship between Age and the Ability to Break Scored Tablets.
AB - BACKGROUND: Practical problems with the use of medicines, such as difficulties
with breaking tablets, are an often overlooked cause for non-adherence. Tablets
frequently break in uneven parts and loss of product can occur due to crumbling
and powdering. Health characteristics, such as the presence of peripheral
neuropathy, decreased grip strength and manual dexterity, can affect a patient's
ability to break tablets. As these impairments are associated with aging and age
related diseases, such as Parkinson's disease and arthritis, difficulties with
breaking tablets could be more prevalent among older adults. The objective of
this study was to investigate the relationship between age and the ability to
break scored tablets. METHODS: A comparative study design was chosen. Thirty-six
older adults and 36 young adults were systematically observed with breaking
scored tablets. Twelve different tablets were included. All participants were
asked to break each tablet by three techniques: in between the fingers with the
use of nails, in between the fingers without the use of nails and pushing the
tablet downward with one finger on a solid surface. It was established whether a
tablet was broken or not, and if broken, whether the tablet was broken accurately
or not. RESULTS: The older adults experienced more difficulties to break tablets
compared to the young adults. On average, the older persons broke 38.1% of the
tablets, of which 71.0% was broken accurately. The young adults broke 78.2% of
the tablets, of which 77.4% was broken accurately. Further analysis by mixed
effects logistic regression revealed that age was associated with the ability to
break tablets, but not with the accuracy of breaking. CONCLUSIONS: Breaking
scored tablets by hand is less successful in an elderly population compared to a
group of young adults. Health care providers should be aware that tablet breaking
is not appropriate for all patients and for all drugs. In case tablet breaking is
unavoidable, a patient's ability to break tablets should be assessed by health
care providers and instructions on the appropriate method of breaking should be
provided.
PMID- 27507947
TI - Scorpion Venom Heat-Resistant Peptide Protects Transgenic Caenorhabditis elegans
from beta-Amyloid Toxicity.
AB - Scorpion venom heat-resistant peptide (SVHRP) is a component purified from Buthus
martensii Karsch scorpion venom. Our previous studies found SVHRP could enhance
neurogenesis and inhibit microglia-mediated neuroinflammation in vivo. Here, we
use the transgenic CL4176, CL2006, and CL2355 strains of Caenorhabditis elegans
which express the human Abeta1-42 to investigate the effects and the possible
mechanisms of SVHRP mediated protection against Abeta toxicity in vivo. The
results showed that SVHRP-fed worms displayed remarkably decreased paralysis,
less abundant toxic Abeta oligomers, reduced Abeta plaque deposition with respect
to untreated animals. SVHRP also suppressed neuronal Abeta expression-induced
defects in chemotaxis behavior and attenuated levels of ROS in the transgenic C.
elegans. Taken together, these results suggest SVHRP could protect against Abeta
induced toxicity in C. elegans. Further studies need to be conducted in murine
models and humans to analyze the effectiveness of the peptide.
PMID- 27507948
TI - Chronic Treatment with Ivabradine Does Not Affect Cardiovascular Autonomic
Control in Rats.
AB - A low resting heart rate (HR) would be of great benefit in cardiovascular
diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated
cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering
drug. Its effects on the autonomic HR control are little known. This study
assessed the effects of chronic treatment with ivabradine on the modulatory,
reflex and tonic cardiovascular autonomic control and on the renal sympathetic
nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving
intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8
consecutive days. Rats were submitted to vessels cannulation to perform arterial
blood pressure (AP) and HR recordings in freely moving rats. Time series of
resting pulse interval and systolic AP were used to measure cardiovascular
variability parameters. We also assessed the baroreflex, chemoreflex and the
Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine
on the autonomic control of the heart, we performed sympathetic and vagal
autonomic blockade. As expected, ivabradine-treated rats showed a lower resting
(VEH: 362 +/- 16 bpm vs. IVA: 260 +/- 14 bpm, p = 0.0005) and intrinsic HR (VEH:
369 +/- 9 bpm vs. IVA: 326 +/- 11 bpm, p = 0.0146). However, the chronic
treatment with ivabradine did not change normalized HR spectral parameters LF
(nu) (VEH: 24.2 +/- 4.6 vs. IVA: 29.8 +/- 6.4; p > 0.05); HF (nu) (VEH: 75.1 +/-
3.7 vs. IVA: 69.2 +/- 5.8; p > 0.05), any cardiovascular reflexes, neither the
tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91+/- 0.02
vs. IVA: 0.88 +/- 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings
in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the
resting HR (VEH: 364 +/- 12 bpm vs. IVA: 207 +/- 11 bpm, p < 0.0001), without
affecting RSNA (VEH: 117 +/- 16 vs. IVA: 120 +/- 9 spikes/s, p = 0.9100) and mean
arterial pressure (VEH: 70 +/- 4 vs. IVA: 77 +/- 6 mmHg, p = 0.3293). Our results
suggest that, in health rats, the long-term treatment with ivabradine directly
reduces the HR without changing the RSNA modulation and the reflex and tonic
autonomic control of the heart.
PMID- 27507949
TI - Development and Clinical Evaluation of an mHealth Application for Stress
Management.
AB - A large number of individuals experience mental health disorders, with cognitive
behavioral therapy (CBT) emerging as a standard practice for reduction in
psychiatric symptoms, including stress, anger, anxiety, and depression. However,
CBT is associated with significant patient dropout and lacks the means to provide
objective data regarding a patient's experience and symptoms between sessions.
Emerging wearables and mobile health (mHealth) applications represent an approach
that may provide objective data to the patient and provider between CBT sessions.
Here, we describe the development of a classifier of real-time physiological
stress in a healthy population (n = 35) and apply it in a controlled clinical
evaluation for armed forces veterans undergoing CBT for stress and anger
management (n = 16). Using cardiovascular and electrodermal inputs from a
wearable device, the classifier was able to detect physiological stress in a non
clinical sample with accuracy greater than 90%. In a small clinical sample,
patients who used the classifier and an associated mHealth application were less
likely to discontinue therapy (p = 0.016, d = 1.34) and significantly improved on
measures of stress (p = 0.032, d = 1.61), anxiety (p = 0.050, d = 1.26), and
anger (p = 0.046, d = 1.41) compared to controls undergoing CBT alone. Given the
large number of individuals that experience mental health disorders and the unmet
need for treatment, especially in developing nations, such mHealth approaches
have the potential to provide or augment treatment at low cost in the absence of
in-person care.
PMID- 27507950
TI - A Deeper Look at the "Neural Correlate of Consciousness".
AB - A main goal of the neuroscience of consciousness is: find the neural correlate to
conscious experiences (NCC). When have we achieved this goal? The answer depends
on our operationalization of "NCC." Chalmers (2000) shaped the widely accepted
operationalization according to which an NCC is a neural system with a state
which is minimally sufficient (but not necessary) for an experience. A deeper
look at this operationalization reveals why it might be unsatisfactory: (i) it is
not an operationalization of a correlate for occurring experiences, but of the
capacity to experience; (ii) it is unhelpful for certain cases which are used to
motivate a search for neural correlates of consciousness; (iii) it does not
mirror the usage of "NCC" by scientists who seek for unique correlates; (iv) it
hardly allows for a form of comparative testing of hypotheses, namely experimenta
crucis. Because of these problems (i-iv), we ought to amend or improve on
Chalmers's operationalization. Here, I present an alternative which avoids these
problems. This "NCC2.0" also retains some benefits of Chalmers's
operationalization, namely being compatible with contributions from extended,
embedded, enacted, or embodied accounts (4E-accounts) and allowing for the
possibility of non-biological or artificial experiencers.
PMID- 27507951
TI - Production and Perception of Tone 3 Focus in Mandarin Chinese.
AB - This study uses production and perception experiments to explore tone 3 focus in
Mandarin Chinese. Overall, contrastive focus in Mandarin is clearly marked with
increased duration, intensity, and pitch range: in the experiments, listeners
identified focused syllables correctly more than 90% of the time. However, a tone
3 syllable offers a smaller capacity for pitch range expansion under focus, and
also yields less intensity increase; in addition, local dissimilation increases
the duration, intensity, and pitch range of adjacent syllables within the same
phrase as a focused tone 3 syllable. As a result, tone 3 focus was less well
identified by listeners (77.1%). We suggest that the relatively poor
identification of tone 3 focus is due to the smaller capacity for pitch range
expansion, the confusion from within-phrase local dissimilatory effects, and the
relatively weak intensity of tone 3. This study demonstrates that even within a
language where purely prosodic marking of focus is clear, the location of
prosodic focus can be difficult to identify in certain circumstances. Our results
underline the conclusion, established in other work, that prosodic marking of
focus is not universal, but is expressed through the prosodic system of each
language.
PMID- 27507952
TI - How Changes in Psychosocial Job Characteristics Impact Burnout in Nurses: A
Longitudinal Analysis.
AB - AIMS: The main aim of this longitudinal study was to test the Job Demand-Control
Support (JDCS) model and to analyze whether changes in psychosocial job
characteristics are related to (changes in) burnout. BACKGROUND: Previous studies
on the effects of JDCS variables on burnout dimensions have indicated that the
iso-strain hypothesis (i.e., high job demands, low control, and low support
additively predict high stress reactions) and the buffer hypotheses (i.e., high
job control and/or social support is expected to moderate the negative impact of
high demands on stress reactions) have hardly been examined concurrently in a
longitudinal design; and that the effects of changes of psychosocial job
variables on burnout dimensions have hardly been analyzed. DESIGN: This two wave
study was carried out over a period of 14 months in a sample of 217 Italian
nurses. METHOD: Hierarchical regression analyses were used to test the cross
lagged main and interactive effects of JDCS variables, and to analyse the across
time effects of changes in JDCS dimensions on burnout variables. RESULTS: The
Time 1 job characteristics explained 2-8% of the variance in the Time 2 burnout
dimensions, but no support for the additive, or the buffer hypothesis of the JDCS
model was found. Changes in job characteristics explained an additional 3-20% of
variance in the Time 2 burnout dimensions. Specifically, high levels of emotional
exhaustion at Time 2 were explained by high levels of social support at Time 1,
and unfavorable changes in demands, control, and support over time; high
depersonalization at Time 2 was explained by high social support at time 1 and by
an increase in demands over time; and high personal accomplishment at Time 2 was
predicted by high demands, high control, interactive effect demands * control *
social support, at Time 1, and by a decrease in demands over time. No reversed
effects of burnout on work characteristics have been found. CONCLUSION: Our
findings suggest that the work environment is subject to changes: the majority of
employees experienced considerable changes in all job conditions over time. These
changes impacted employee burnout. Limitations and implications of the study are
discussed.
PMID- 27507953
TI - Cultural Affordances: Scaffolding Local Worlds Through Shared Intentionality and
Regimes of Attention.
AB - In this paper we outline a framework for the study of the mechanisms involved in
the engagement of human agents with cultural affordances. Our aim is to better
understand how culture and context interact with human biology to shape human
behavior, cognition, and experience. We attempt to integrate several related
approaches in the study of the embodied, cognitive, and affective substrates of
sociality and culture and the sociocultural scaffolding of experience. The
integrative framework we propose bridges cognitive and social sciences to provide
(i) an expanded concept of 'affordance' that extends to sociocultural forms of
life, and (ii) a multilevel account of the socioculturally scaffolded forms of
affordance learning and the transmission of affordances in patterned
sociocultural practices and regimes of shared attention. This framework provides
an account of how cultural content and normative practices are built on a
foundation of contentless basic mental processes that acquire content through
immersive participation of the agent in social practices that regulate joint
attention and shared intentionality.
PMID- 27507954
TI - The Effects of General System Justification on Corruption Perception and Intent.
AB - Previous research stresses that system justifying belief can weaken corruption
perception, by this possibly fostering unjust behaviors. However, general results
of the effect of general system justification on corruption are ambiguous,
indicating also a lessening impact. We conducted a line of studies trying to
elucidate these circumstances by testing the effect of general system
justification on corruption perception and intention. In addition, we explored
institutional trust as a possible mediator in this process. For this purpose, we
conducted three studies. The first two studies examined the association between
general system justification and corruption. In Study 1, a correlational design
was run using questionnaires to assess the relation between general system
justification and corruption perception as well as corruption intention. In Study
2, an experimental design was conducted manipulating general system justification
via exposure to high or low system threat condition, then measuring its effect on
corruption perception and corrupt intention. In Study 3, two sub-studies using
correlational and experimental designs were run to explore the mediating role of
institutional trust, respectively. Results replicated former studies showing that
general system justification is negatively associated with corruption perception.
However, they also showed a negative correlation with corrupt intention.
Furthermore, they showed that institutional trust mediated the relation between
general system justification and corruption. We suggest to consider these
findings to further elucidate the psychological basis underlying different
effects of general system justification on human behaviors.
PMID- 27507955
TI - Encouraging Realistic Expectations in STEM Students: Paradoxical Effects of a
Motivational Intervention.
AB - College students in STEM (science, technology, engineering, mathematics)
disciplines are increasingly faced with highly competitive and demanding degree
programs and are at risk of academic overconfidence. Following from theory and
research highlighting the psychological and developmental risks of unrealistic
expectations, the present exploratory study evaluated the longitudinal effects of
a motivational intervention encouraging college students in STEM degree programs
(N = 52) to consider the importance of downgrading one's expectations in response
to academic setbacks. Contrary to study hypotheses, the results showed
intervention participants to report significantly higher expectations and
optimism on post-test measures administered 4 months later, no significant gains
in emotional well-being or achievement goal orientations, and lower GPAs over
five subsequent semesters. These paradoxical effects underscore the need for
additional larger-scale research on the nature of students' responses to
potentially ego-threatening motivational programs in STEM disciplines so as to
minimize achievement deficits at the expense of preserving motivational
resources.
PMID- 27507956
TI - Implicit and Explicit Gender Beliefs in Spatial Ability: Stronger Stereotyping in
Boys than Girls.
AB - Sex differences in spatial ability are a seriously debated topic, given the
importance of spatial ability for success in the fields of science, technology,
engineering, and mathematics (STEM) and girls' underrepresentation in these
domains. In the current study we investigated the presence of stereotypic gender
beliefs on spatial ability (i.e., "spatial ability is for boys") in 10- and 12
year-old children. We used both an explicit measure (i.e., a self-report
questionnaire) and an implicit measure (i.e., a child IAT). Results of the
explicit measure showed that both sexes associated spatial ability with boys,
with boys holding more male stereotyped attitudes than girls. On the implicit
measure, boys associated spatial ability with boys, while girls were gender
neutral. In addition, we examined the effects of gender beliefs on spatial
performance, by experimentally activating gender beliefs within a pretest
instruction-posttest design. We compared three types of instruction: boys are
better, girls are better, and no sex differences. No effects of these gender
belief instructions were found on children's spatial test performance (i.e.,
mental rotation and paper folding). The finding that children of this age already
have stereotypic beliefs about the spatial capacities of their own sex is
important, as these beliefs may influence children's choices for spatial leisure
activities and educational tracks in the STEM domain.
PMID- 27507957
TI - Neuroplasticity and Clinical Practice: Building Brain Power for Health.
AB - The focus of this review is on driving neuroplasticity in a positive direction
using evidence-based interventions that also have the potential to improve
general health. One goal is to provide an overview of the many ways new
neuroscience can inform treatment protocols to empower and motivate clients to
make the lifestyle choices that could help build brain power and could increase
adherence to healthy lifestyle changes that have also been associated with
simultaneously enhancing vigorous longevity, health, happiness, and wellness.
Another goal is to explore the use of a focus in clinical practice on helping
clients appreciate this new evidence and use evolving neuroscience in
establishing individualized goals, designing strategies for achieving them and
increasing treatment compliance. The timing is urgent for such interventions with
goals of enhancing brain health across the lifespan and improving statistics on
dementia worldwide.
PMID- 27507958
TI - Schizophrenia Spectrum Disorders Show Reduced Specificity and Less Positive
Events in Mental Time Travel.
AB - Mental time travel refers to the ability to recall past events and to imagine
possible future events. Schizophrenia (SCZ) patients have problems in remembering
specific personal experiences in the past and imagining what will happen in the
future. This study aimed to examine episodic past and future thinking in SCZ
spectrum disorders including SCZ patients and individuals with schizotypal
personality disorder (SPD) proneness who are at risk for developing SCZ. Thirty
two SCZ patients, 30 SPD proneness individuals, and 33 healthy controls
participated in the study. The Sentence Completion for Events from the Past Test
(SCEPT) and the Sentence Completion for Events in the Future Test were used to
measure past and future thinking abilities. Results showed that SCZ patients
showed significantly reduced specificity in recalling past and imagining future
events, they generated less proportion of specific and extended events compared
to healthy controls. SPD proneness individuals only generated less extended
events compared to healthy controls. The reduced specificity was mainly
manifested in imagining future events. Both SCZ patients and SPD proneness
individuals generated less positive events than controls. These results suggest
that mental time travel impairments in SCZ spectrum disorders and have
implications for understanding their cognitive and emotional deficits.
PMID- 27507959
TI - Analysis of Metagenomics Next Generation Sequence Data for Fungal ITS Barcoding:
Do You Need Advance Bioinformatics Experience?
AB - During the last few decades, most of microbiology laboratories have become
familiar in analyzing Sanger sequence data for ITS barcoding. However, with the
availability of next-generation sequencing platforms in many centers, it has
become important for medical mycologists to know how to make sense of the massive
sequence data generated by these new sequencing technologies. In many reference
laboratories, the analysis of such data is not a big deal, since suitable IT
infrastructure and well-trained bioinformatics scientists are always available.
However, in small research laboratories and clinical microbiology laboratories
the availability of such resources are always lacking. In this report, simple and
user-friendly bioinformatics work-flow is suggested for fast and reproducible ITS
barcoding of fungi.
PMID- 27507960
TI - The Potential Role of Arbuscular Mycorrhizal Fungi in the Restoration of Degraded
Lands.
AB - Experiences worldwide reveal that degraded lands restoration projects achieve
little success or fail. Hence, understanding the underlying causes and
accordingly, devising appropriate restoration mechanisms is crucial. In doing so,
the ever-increasing aspiration and global commitments in degraded lands
restoration could be realized. Here we explain that arbuscular mycorrhizal fungi
(AMF) biotechnology is a potential mechanism to significantly improve the
restoration success of degraded lands. There are abundant scientific evidences to
demonstrate that AMF significantly improve soil attributes, increase above and
belowground biodiversity, significantly improve tree/shrub seedlings survival,
growth and establishment on moisture and nutrient stressed soils. AMF have also
been shown to drive plant succession and may prevent invasion by alien species.
The very few conditions where infective AMF are low in abundance and diversity is
when the soil erodes, is disturbed and is devoid of vegetation cover. These are
all common features of degraded lands. Meanwhile, degraded lands harbor low
levels of infective AMF abundance and diversity. Therefore, the successful
restoration of infective AMF can potentially improve the restoration success of
degraded lands. Better AMF inoculation effects result when inocula are composed
of native fungi instead of exotics, early seral instead of late seral fungi, and
are consortia instead of few or single species. Future research efforts should
focus on AMF effect on plant community primary productivity and plant
competition. Further investigation focusing on forest ecosystems, and carried out
at the field condition is highly recommended. Devising cheap and ethically widely
accepted inocula production methods and better ways of AMF in situ management for
effective restoration of degraded lands will also remain to be important research
areas.
PMID- 27507961
TI - Comparison of Fusarium graminearum Transcriptomes on Living or Dead Wheat
Differentiates Substrate-Responsive and Defense-Responsive Genes.
AB - Fusarium graminearum is an opportunistic pathogen of cereals where it causes
severe yield losses and concomitant mycotoxin contamination of the grains. The
pathogen has mixed biotrophic and necrotrophic (saprophytic) growth phases during
infection and the regulatory networks associated with these phases have so far
always been analyzed together. In this study we compared the transcriptomes of
fungal cells infecting a living, actively defending plant representing the mixed
live style (pathogenic growth on living flowering wheat heads) to the response of
the fungus infecting identical, but dead plant tissues (cold-killed flowering
wheat heads) representing strictly saprophytic conditions. We found that the
living plant actively suppressed fungal growth and promoted much higher toxin
production in comparison to the identical plant tissue without metabolism
suggesting that molecules signaling secondary metabolite induction are not pre
existing or not stable in the plant in sufficient amounts before infection.
Differential gene expression analysis was used to define gene sets responding to
the active or the passive plant as main impact factor and driver for gene
expression. We correlated our results to the published F. graminearum
transcriptomes, proteomes, and secretomes and found that only a limited number of
in planta- expressed genes require the living plant for induction but the
majority uses simply the plant tissue as signal. Many secondary metabolite (SM)
gene clusters show a heterogeneous expression pattern within the cluster
indicating that different genetic or epigenetic signals govern the expression of
individual genes within a physically linked cluster. Our bioinformatic approach
also identified fungal genes which were actively repressed by signals derived
from the active plant and may thus represent direct targets of the plant defense
against the invading pathogen.
PMID- 27507962
TI - Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow
Cytometry.
AB - Rapidly treating infections with adequate antibiotics is of major importance.
This requires a fast and accurate determination of the antibiotic susceptibility
of bacterial pathogens. The most frequently used methods are slow because they
are based on the measurement of growth inhibition. Faster methods, such as PCR
based detection of determinants of antibiotic resistance, do not always provide
relevant information on susceptibility, particularly that which is not
genetically based. Consequently, new methods, such as the detection of changes in
bacterial physiology caused by antibiotics using flow cytometry and fluorescent
viability markers, are being explored. In this study, we assessed whether Alexa
Fluor(r) 633 Hydrazide (AFH), which targets carbonyl groups, can be used for
antibiotic susceptibility testing. Carbonylation of cellular macromolecules,
which increases in antibiotic-treated cells, is a particularly appropriate to
assess for this purpose because it is irreversible. We tested the susceptibility
of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas
aeruginosa, to antibiotics from the three classes: beta-lactams, aminoglycosides,
and fluoroquinolones. In addition to AFH, we used TO-PRO(r)-3, which enters cells
with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with
depolarized membranes. We also monitored antibiotic-induced morphological
alterations of bacterial cells by analyzing light scattering signals. Although
all tested dyes and light scattering signals allowed for the detection of
antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and
reliable detection of antibiotic susceptibility.
PMID- 27507963
TI - Pea Broth Enhances the Biocontrol Efficacy of Lysobacter capsici AZ78 by
Triggering Cell Motility Associated with Biogenesis of Type IV Pilus.
AB - Bacterial cells can display different types of motility, due to the presence of
external appendages such as flagella and type IV pili. To date, little
information on the mechanisms involved in the motility of the Lysobacter species
has been available. Recently, L. capsici AZ78, a biocontrol agent of
phytopathogenic oomycetes, showed the ability to move on jellified pea broth. Pea
broth medium improved also the biocontrol activity of L. capsici AZ78 against
Plasmopara viticola under greenhouse conditions. Noteworthy, the quantity of pea
residues remaining on grapevine leaves fostered cell motility in L. capsici AZ78.
Based on these results, this unusual motility related to the composition of the
growth medium was investigated in bacterial strains belonging to several
Lysobacter species. The six L. capsici strains tested developed dendrite-like
colonies when grown on jellified pea broth, while the development of dendrite
like colonies was not recorded in the media commonly used in motility assays. To
determine the presence of genes responsible for biogenesis of the flagellum and
type IV pili, the genome of L. capsici AZ78 was mined. Genes encoding structural
components and regulatory factors of type IV pili were upregulated in L. capsici
AZ78 cells grown on the above-mentioned medium, as compared with the other tested
media. These results provide new insight into the motility mechanism of L.
capsici members and the role of type IV pili and pea compounds on the epiphytic
fitness and biocontrol features of L. capsici AZ78.
PMID- 27507965
TI - The FlgT Protein Is Involved in Aeromonas hydrophila Polar Flagella Stability and
Not Affects Anchorage of Lateral Flagella.
AB - Aeromonas hydrophila sodium-driven polar flagellum has a complex stator-motor.
Consist of two sets of redundant and non-exchangeable proteins (PomA/PomB and
PomA2/PomB2), which are homologs to other sodium-conducting polar flagellum
stator motors; and also two essential proteins (MotX and MotY), that they
interact with one of those two redundant pairs of proteins and form the T-ring.
In this work, we described an essential protein for polar flagellum stability and
rotation which is orthologs to Vibrio spp. FlgT and it is encoded outside of the
A. hydrophila polar flagellum regions. The flgT was present in all mesophilic
Aeromonas strains tested and also in the non-motile Aeromonas salmonicida. The A.
hydrophila DeltaflgT mutant is able to assemble the polar flagellum but is more
unstable and released into the culture supernatant from the cell upon completion
assembly. Presence of FlgT in purified polar hook-basal bodies (HBB) of wild-type
strain was confirmed by Western blotting and electron microscopy observations
showed an outer ring of the T-ring (H-ring) which is not present in the DeltaflgT
mutant. Anchoring and motility of proton-driven lateral flagella was not affected
in the DeltaflgT mutant and specific antibodies did not detect FlgT in purified
lateral HBB of wild type strain.
PMID- 27507964
TI - Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds
Affecting Human Health.
AB - The gut microbiota is composed of a huge number of different bacteria, that
produce a large amount of compounds playing a key role in microbe selection and
in the construction of a metabolic signaling network. The microbial activities
are affected by environmental stimuli leading to the generation of a wide number
of compounds, that influence the host metabolome and human health. Indeed,
metabolite profiles related to the gut microbiota can offer deep insights on the
impact of lifestyle and dietary factors on chronic and acute diseases.
Metagenomics, metaproteomics and metabolomics are some of the meta-omics
approaches to study the modulation of the gut microbiota. Metabolomic research
applied to biofluids allows to: define the metabolic profile; identify and
quantify classes and compounds of interest; characterize small molecules produced
by intestinal microbes; and define the biochemical pathways of metabolites. Mass
spectrometry and nuclear magnetic resonance spectroscopy are the principal
technologies applied to metabolomics in terms of coverage, sensitivity and
quantification. Moreover, the use of biostatistics and mathematical approaches
coupled with metabolomics play a key role in the extraction of biologically
meaningful information from wide datasets. Metabolomic studies in gut microbiota
related research have increased, focusing on the generation of novel biomarkers,
which could lead to the development of mechanistic hypotheses potentially
applicable to the development of nutritional and personalized therapies.
PMID- 27507966
TI - Changes in the Structure of the Microbial Community Associated with
Nannochloropsis salina following Treatments with Antibiotics and Bioactive
Compounds.
AB - Open microalgae cultures host a myriad of bacteria, creating a complex system of
interacting species that influence algal growth and health. Many algal microbiota
studies have been conducted to determine the relative importance of bacterial
taxa to algal culture health and physiological states, but these studies have not
characterized the interspecies relationships in the microbial communities. We
subjected Nanochroloropsis salina cultures to multiple chemical treatments
(antibiotics and quorum sensing compounds) and obtained dense time-series data on
changes to the microbial community using 16S gene amplicon metagenomic sequencing
(21,029,577 reads for 23 samples) to measure microbial taxa-taxa abundance
correlations. Short-term treatment with antibiotics resulted in substantially
larger shifts in the microbiota structure compared to changes observed following
treatment with signaling compounds and glucose. We also calculated operational
taxonomic unit (OTU) associations and generated OTU correlation networks to
provide an overview of possible bacterial OTU interactions. This analysis
identified five major cohesive modules of microbiota with similar co-abundance
profiles across different chemical treatments. The Eigengenes of OTU modules were
examined for correlation with different external treatment factors. This
correlation-based analysis revealed that culture age (time) and treatment types
have primary effects on forming network modules and shaping the community
structure. Additional network analysis detected Alteromonadeles and
Alphaproteobacteria as having the highest centrality, suggesting these species
are "keystone" OTUs in the microbial community. Furthermore, we illustrated that
the chemical tropodithietic acid, which is secreted by several species in the
Alphaproteobacteria taxon, is able to drastically change the structure of the
microbiota within 3 h. Taken together, these results provide valuable insights
into the structure of the microbiota associated with N. salina cultures and how
these structures change in response to chemical perturbations.
PMID- 27507967
TI - Characterization of Outer Membrane Proteome of Akkermansia muciniphila Reveals
Sets of Novel Proteins Exposed to the Human Intestine.
AB - Akkermansia muciniphila is a common member of the human gut microbiota and
belongs to the Planctomycetes-Verrucomicrobia-Chlamydiae superphylum. Decreased
levels of A. muciniphila have been associated with many diseases, and thus it is
considered to be a beneficial resident of the intestinal mucus layer. Surface
exposed molecules produced by this organism likely play important roles in
colonization and communication with other microbes and the host, but the protein
composition of the outer membrane (OM) has not been characterized thus far.
Herein we set out to identify and characterize A. muciniphila proteins using an
integrated approach of proteomics and computational analysis. Sarkosyl extraction
and sucrose density-gradient centrifugation methods were used to enrich and
fractionate the OM proteome of A. muciniphila. Proteins from these fractions were
identified by LC-MS/MS and candidates for OM proteins derived from the
experimental approach were subjected to computational screening to verify their
location in the cell. In total we identified 79 putative OM and membrane
associated extracellular proteins, and 23 of those were found to differ in
abundance between cells of A. muciniphila grown on the natural substrate, mucin,
and those grown on the non-mucus sugar, glucose. The identified OM proteins
included highly abundant proteins involved in secretion and transport, as well as
proteins predicted to take part in formation of the pili-like structures observed
in A. muciniphila. The most abundant OM protein was a 95-kD protein, termed PilQ,
annotated as a type IV pili secretin and predicted to be involved in the
production of pili in A. muciniphila. To verify its location we purified the His
Tag labeled N-terminal domain of PilQ and generated rabbit polyclonal antibodies.
Immunoelectron microscopy of thin sections immunolabeled with these antibodies
demonstrated the OM localization of PilQ, testifying for its predicted function
as a type IV pili secretin in A. muciniphila. As pili structures are known to be
involved in the modulation of host immune responses, this provides support for
the involvement of OM proteins in the host interaction of A. muciniphila. In
conclusion, the characterization of A. muciniphila OM proteome provides valuable
information that can be used for further functional and immunological studies.
PMID- 27507968
TI - Engineering of Helicobacter pylori Dimeric Oxidoreductase DsbK (HP0231).
AB - The formation of disulfide bonds that are catalyzed by proteins of the Dsb
(disulfide bond) family is crucial for the correct folding of many
extracytoplasmic proteins. Thus, this formation plays an essential, pivotal role
in the assembly of many virulence factors. The Helicobacter pylori disulfide bond
forming system is uncomplicated compared to the best-characterized Escherichia
coli Dsb pathways. It possesses only two extracytoplasmic Dsb proteins named
HP0377 and HP0231. As previously shown, HP0377 is a reductase involved in the
process of cytochrome c maturation. Additionally, it also possesses disulfide
isomerase activity. HP0231 was the first periplasmic dimeric oxidoreductase
involved in disulfide generation to be described. Although HP0231 function is
critical for oxidative protein folding, its structure resembles that of dimeric
EcDsbG, which does not confer this activity. However, the HP0231 catalytic motifs
(CXXC and the so-called cis-Pro loop) are identical to that of monomeric EcDsbA.
To understand the functioning of HP0231, we decided to study the relations
between its sequence, structure and activity through an extensive analysis of
various HP0231 point mutants, using in vivo and in vitro strategies. Our work
shows the crucial role of the cis-Pro loop, as changing valine to threonine in
this motif completely abolishes the protein function in vivo. Functioning of
HP0231 is conditioned by the combination of CXXC and the cis-Pro loop, as
replacing the HP0231 CXXC motif by the motif from EcDsbG or EcDsbC results in
bifunctional protein, at least in E. coli. We also showed that the dimerization
domain of HP0231 ensures contact with its substrates. Moreover, the activity of
this oxidase is independent on the structure of the catalytic domain. Finally, we
showed that HP0231 chaperone activity is independent of its redox function.
PMID- 27507969
TI - Flavoprotein-Mediated Tellurite Reduction: Structural Basis and Applications to
the Synthesis of Tellurium-Containing Nanostructures.
AB - The tellurium oxyanion tellurite (TeO3 (2-)) is extremely harmful for most
organisms. It has been suggested that a potential bacterial tellurite resistance
mechanism would consist of an enzymatic, NAD(P)H-dependent, reduction to the less
toxic form elemental tellurium (Te(0)). To date, a number of enzymes such as
catalase, type II NADH dehydrogenase and terminal oxidases from the electron
transport chain, nitrate reductases, and dihydrolipoamide dehydrogenase (E3),
among others, have been shown to display tellurite-reducing activity. This
activity is generically referred to as tellurite reductase (TR). Bioinformatic
data resting on some of the abovementioned enzymes enabled the identification of
common structures involved in tellurite reduction including vicinal catalytic
cysteine residues and the FAD/NAD(P)(+)-binding domain, which is characteristic
of some flavoproteins. Along this line, thioredoxin reductase (TrxB), alkyl
hydroperoxide reductase (AhpF), glutathione reductase (GorA), mercuric reductase
(MerA), NADH: flavorubredoxin reductase (NorW), dihydrolipoamide dehydrogenase,
and the putative oxidoreductase YkgC from Escherichia coli or environmental
bacteria were purified and assessed for TR activity. All of them displayed in
vitro TR activity at the expense of NADH or NADPH oxidation. In general, optimal
reducing conditions occurred around pH 9-10 and 37 degrees C. Enzymes exhibiting
strong TR activity produced Te-containing nanostructures (TeNS). While GorA and
AhpF generated TeNS of 75 nm average diameter, E3 and YkgC produced larger
structures (>100 nm). Electron-dense structures were observed in cells over
expressing genes encoding TrxB, GorA, and YkgC.
PMID- 27507970
TI - Regulatory RNAs in the Less Studied Streptococcal Species: From Nomenclature to
Identification.
AB - Streptococcal species are Gram-positive bacteria involved in severe and invasive
diseases in humans and animals. Although, this group includes different
pathogenic species involved in life-threatening infections for humans, it also
includes beneficial species, such as Streptococcus thermophilus, which is used in
yogurt production. In bacteria virulence factors are controlled by various
regulatory networks including regulatory RNAs. For clearness and to develop
logical thinking, we start this review with a revision of regulatory RNAs
nomenclature. Previous reviews are mostly dealing with Streptococcus pyogenes and
Streptococcus pneumoniae regulatory RNAs. We especially focused our analysis on
regulatory RNAs in Streptococcus agalactiae, Streptococcus mutans, Streptococcus
thermophilus and other less studied Streptococcus species. Although, S.
agalactiae RNome remains largely unknown, sRNAs (small RNAs) are supposed to
mediate regulation during environmental adaptation and host infection. In the
case of S. mutans, sRNAs are suggested to be involved in competence regulation,
carbohydrate metabolism, and Toxin-Antitoxin systems. A new category of miRNA
size small RNAs (msRNAs) was also identified for the first time in this species.
The analysis of S. thermophilus sRNome shows that many sRNAs are associated to
the bacterial immune system known as CRISPR-Cas system. Only few of the other
different Streptococcus species have been the subject of studies pointed toward
the characterization of regulatory RNAs. Finally, understanding bacterial sRNome
can constitute one step forward to the elaboration of new strategies in therapy
such as substitution of antibiotics in the management of S. agalactiae neonatal
infections, prevention of S. mutans dental caries or use of S. thermophilus
CRISPR-Cas system in genome editing applications.
PMID- 27507971
TI - Melanoma Affects the Composition of Blood Cell-Derived Extracellular Vesicles.
AB - Extracellular vesicles (EVs) are specifically loaded with nucleic acids, lipids,
and proteins from their parental cell. Therefore, the constitution of EVs
reflects the type and status of the originating cell and EVs in melanoma
patient's plasma could be indicative for the tumor. Likewise, EVs might influence
tumor progression by regulating immune responses. We performed a broad protein
characterization of EVs from plasma of melanoma patients and healthy donors as
well as from T cells, B cells, natural killer (NK) cells, monocytes, monocyte
derived dendritic cells (moDCs), and platelets using a multiplex bead-based
platform. Using this method, we succeeded in analyzing 58 proteins that were
differentially displayed on EVs. Hierarchical clustering of protein intensity
patterns grouped EVs according to their originating cell type. The analysis of
EVs from stimulated B cells and moDCs revealed the transfer of surface proteins
to vesicles depending on the cell status. The protein profiles of plasma vesicles
resembled the protein profiles of EVs from platelets, antigen-presenting cells
and NK cells as shown by platelet markers, co-stimulatory proteins, and a NK cell
subpopulation marker. In comparison to healthy plasma vesicles, melanoma plasma
vesicles showed altered signals for platelet markers, indicating a changed
vesicle secretion or protein loading of EVs by platelets and a lower CD8 signal
that might be associated with a diminished activity of NK cells or T cells. As we
hardly detected melanoma-derived vesicles in patient's plasma, we concluded that
blood cells induced the observed differences. In summary, our results question a
direct effect of melanoma cells on the composition of EVs in melanoma plasma, but
rather argue for an indirect influence of melanoma cells on the vesicle secretion
or vesicle protein loading by blood cells.
PMID- 27507972
TI - Extracellular Release and Signaling by Heat Shock Protein 27: Role in Modifying
Vascular Inflammation.
AB - Heat shock protein 27 (HSP27) is traditionally viewed as an intracellular
chaperone protein with anti-apoptotic properties. However, recent data indicate
that a number of heat shock proteins, including HSP27, are also found in the
extracellular space where they may signal via membrane receptors to alter gene
transcription and cellular function. Therefore, there is increasing interest in
better understanding how HSP27 is released from cells, its levels and composition
in the extracellular space, and the cognate cell membrane receptors involved in
effecting cell signaling. In this paper, the knowledge to date, as well as some
emerging paradigms about the extracellular function of HSP27 is presented. Of
particular interest is the role of HSP27 in attenuating atherogenesis by
modifying lipid uptake and inflammation in the plaque. Moreover, the abundance of
HSP27 in serum is an emerging new biomarker for ischemic events. Finally, HSP27
replacement therapy may represent a novel therapeutic opportunity for chronic
inflammatory disorders, such as atherosclerosis.
PMID- 27507974
TI - Cytogenetic Diversity of Simple Sequences Repeats in Morphotypes of Brassica rapa
ssp. chinensis.
AB - A significant fraction of the nuclear DNA of all eukaryotes is comprised of
simple sequence repeats (SSRs). Although these sequences are widely used for
studying genetic variation, linkage mapping and evolution, little attention had
been paid to the chromosomal distribution and cytogenetic diversity of these
sequences. In this paper, we report the distribution characterization of mono-,
di-, and tri-nucleotide SSRs in Brassica rapa ssp. chinensis. Fluorescence in
situ hybridization was used to characterize the cytogenetic diversity of SSRs
among morphotypes of B. rapa ssp. chinensis. The proportion of different SSR
motifs varied among morphotypes of B. rapa ssp. chinensis, with tri-nucleotide
SSRs being more prevalent in the genome of B. rapa ssp. chinensis. We determined
the chromosomal locations of mono-, di-, and tri-nucleotide repeat loci. The
results showed that the chromosomal distribution of SSRs in the different
morphotypes is non-random and motif-dependent, and allowed us to characterize the
relative variability in terms of SSR numbers and similar chromosomal
distributions in centromeric/peri-centromeric heterochromatin. The differences
between SSR repeats with respect to abundance and distribution indicate that SSRs
are a driving force in the genomic evolution of B. rapa species. Our results
provide a comprehensive view of the SSR sequence distribution and evolution for
comparison among morphotypes B. rapa ssp. chinensis.
PMID- 27507973
TI - Proteometabolomic Study of Compatible Interaction in Tomato Fruit Challenged with
Sclerotinia rolfsii Illustrates Novel Protein Network during Disease Progression.
AB - Fruit is an assimilator of metabolites, nutrients, and signaling molecules, thus
considered as potential target for pathogen attack. In response to patho-stress,
such as fungal invasion, plants reorganize their proteome, and reconfigure their
physiology in the infected organ. This remodeling is coordinated by a poorly
understood signal transduction network, hormonal cascades, and metabolite
reallocation. The aim of the study was to explore organ-based proteomic
alterations in the susceptibility of heterotrophic fruit to necrotrophic fungal
attack. We conducted time-series protein profiling of Sclerotinia rolfsii invaded
tomato (Solanum lycopersicum) fruit. The differential display of proteome
revealed 216 patho-stress responsive proteins (PSRPs) that change their abundance
by more than 2.5-fold. Mass spectrometric analyses led to the identification of
56 PSRPs presumably involved in disease progression; regulating diverse functions
viz. metabolism, signaling, redox homeostasis, transport, stress-response,
protein folding, modification and degradation, development. Metabolome study
indicated differential regulation of organic acid, amino acids, and carbohydrates
paralleling with the proteomics analysis. Further, we interrogated the proteome
data using network analysis that identified two significant functional protein
hubs centered around malate dehydrogenase, T-complex protein 1 subunit gamma, and
ATP synthase beta. This study reports, for the first-time, kinetically controlled
patho-stress responsive protein network during post-harvest storage in a sink
tissue, particularly fruit and constitute the basis toward understanding the
onset and context of disease signaling and metabolic pathway alterations. The
network representation may facilitate the prioritization of candidate proteins
for quality improvement in storage organ.
PMID- 27507975
TI - Characterization of Shikonin Derivative Secretion in Lithospermum erythrorhizon
Hairy Roots as a Model of Lipid-Soluble Metabolite Secretion from Plants.
AB - Shikonin derivatives are specialized lipophilic metabolites, secreted in abundant
amounts from the root epidermal cells of Lithospermum erythrorhizon. Because they
have anti-microbial activities, these compounds, which are derivatives of red
naphthoquinone, are thought to serve as a chemical barrier for plant roots. The
mechanism by which they are secreted from cells is, however, largely unknown. The
shikonin production system in L. erythrorhizon is an excellent model for studying
the mechanism by which lipophilic compounds are secreted from plant cells,
because of the abundant amounts of these compounds produced by L. erythrorhizon,
the 0 to 100% inducibility of their production, the light-specific inhibition of
production, and the visibility of these products as red pigments. To date, many
factors regulating shikonin biosynthesis have been identified, but no mechanism
that regulates shikonin secretion without inhibiting biosynthesis has been
detected. This study showed that inhibitors of membrane traffic strongly inhibit
shikonin secretion without inhibiting shikonin production, suggesting that the
secretion of shikonin derivatives into the apoplast utilizes pathways common to
the ADP-ribosylation factor/guanine nucleotide exchange factor (ARF/GEF) system
and actin filament polymerization, at least in part. These findings provide clues
about the machinery involved in secreting lipid-soluble metabolites from cells.
PMID- 27507976
TI - Natural Genetic Variation of Seed Micronutrients of Arabidopsis thaliana Grown in
Zinc-Deficient and Zinc-Amended Soil.
AB - The quality of edible seeds for human and animal nutrition is crucially dependent
on high zinc (Zn) and iron (Fe) seed concentrations. The micronutrient
bioavailability is strongly reduced by seed phytate that forms complexes with
seed cations. Superior genotypes with increased seed Zn concentrations had been
identified, but low micronutrient seed levels often prevail when the plants are
grown in Zn-deficient soils, which are globally widespread and correlate with
human Zn-deficiency. Here, seed Zn concentrations of Arabidopsis accessions grown
in Zn-deficient and Zn-amended conditions were measured together with seed Fe and
manganese (Mn), in a panel of 108 accessions. By applying genome-wide
association, de novo candidate genes potentially involved in the seed
micronutrient accumulation were identified. However, a candidate inositol 1,3,4
trisphosphate 5/6-kinase 3 gene (ITPK3), located close to a significant
nucleotide polymorphism associated with relative Zn seed concentrations, was
dispensable for seed micronutrients accumulation in Col-0. Loss of this gene in
itpk3-1 did neither affect phytate seed levels, nor seed Zn, Fe, and Mn. It is
concluded that large natural variance of micronutrient seed levels is identified
in the population and several accessions maintain high seed Zn despite growth in
Zn-deficient conditions.
PMID- 27507977
TI - Identification of Drought Tolerant Mechanisms in Maize Seedlings Based on
Transcriptome Analysis of Recombination Inbred Lines.
AB - Zea mays is an important crop that is sensitive to drought stress, but survival
rates and growth status remain strong in some drought-tolerant lines under stress
conditions. Under drought conditions, many biological processes, such as
photosynthesis, carbohydrate metabolism and energy metabolism, are suppressed,
while little is known about how the transcripts of genes respond to drought
stress in the genome-wide rang in the seedling stage. In our study, the
transcriptome profiles of two maize recombination inbred lines (drought-tolerant
RIL70 and drought-sensitive RIL93) were analyzed at different drought stages to
elucidate the dynamic mechanisms underlying drought tolerance in maize seedlings
during drought conditions. Different numbers of differentially expressed genes
presented in the different stages of drought stress in the two RILs, for the
numbers of RIL93 vs. RIL70 were: 9 vs. 358, 477 vs. 103, and 5207 vs. 152
respectively in DT1, DT2, and DT5. Gene Ontology enrichment analysis revealed
that in the initial drought-stressed stage, the primary differentially expressed
genes involved in cell wall biosynthesis and transmembrane transport biological
processes were overrepresented in RIL70 compared to RIL93. On the contrary,
differentially expressed genes profiles presented at 2 and 5 day-treatments, the
primary differentially expressed genes involved in response to stress, protein
folding, oxidation-reduction, photosynthesis and carbohydrate metabolism, were
overrepresented in RIL93 compared to RIL70. In addition, the transcription of
genes encoding key members of the cell cycle and cell division processes were
blocked, but ABA- and programmed cell death-related processes responded
positively in RIL93. In contrast, the expression of cell cycle genes, ABA- and
programmed cell death-related genes was relatively stable in RIL70. The results
we obtained supported the working hypothesis that signaling events associated
with turgor homeostasis, as established by cell wall biosynthesis regulation- and
aquaporin-related genes, responded early in RIL70, which led to more efficient
detoxification signaling (response to stress, protein folding, oxidation
reduction) during drought stress. This energy saving response at the early stages
of drought should facilitate more cell activity under stress conditions and
result in drought tolerance in RIL70.
PMID- 27507978
TI - The Root Hair Specific SYP123 Regulates the Localization of Cell Wall Components
and Contributes to Rizhobacterial Priming of Induced Systemic Resistance.
AB - Root hairs are important for nutrient and water uptake and are also critically
involved the interaction with soil inhabiting microbiota. Root hairs are tubular
shaped outgrowths that emerge from trichoblasts. This polarized elongation is
maintained and regulated by a robust mechanism involving the endomembrane
secretory and endocytic system. Members of the syntaxin family of SNAREs (soluble
N-ethylmaleimide-sensitive factor attachment protein receptor) in plants (SYP),
have been implicated in regulation of the fusion of vesicles with the target
membranes in both exocytic and endocytic pathways. One member of this family,
SYP123, is expressed specifically in the root hairs and accumulated in the
growing tip region. This study shows evidence of the SYP123 role in polarized
trafficking using knockout insertional mutant plants. We were able to observe
defects in the deposition of cell wall proline rich protein PRP3 and cell wall
polysaccharides. In a complementary strategy, similar results were obtained using
a plant expressing a dominant negative soluble version of SYP123 (SP2 fragment)
lacking the transmembrane domain. The evidence presented indicates that SYP123 is
also regulating PRP3 protein distribution by recycling by endocytosis. We also
present evidence that indicates that SYP123 is necessary for the response of
roots to plant growth promoting rhizobacterium (PGPR) in order to trigger trigger
induced systemic response (ISR). Plants with a defective SYP123 function were
unable to mount a systemic acquired resistance in response to bacterial pathogen
infection and ISR upon interaction with rhizobacteria. These results indicated
that SYP123 was involved in the polarized localization of protein and
polysaccharides in growing root hairs and that this activity also contributed to
the establishment of effective plant defense responses. Root hairs represent very
plastic structures were many biotic and abiotic factors can affect the number,
anatomy and physiology of root hairs. Here, we presented evidence that indicates
that interactions with soil PGPR could be closely regulated by signaling
involving secretory and/or endocytic trafficking at the root hair tip as a quick
way to response to changing environmental conditions.
PMID- 27507979
TI - Is the Invasive Species Listronotus bonariensis (Kuschel) (Coleoptera:
Curculionidae) (Argentine Stem Weevil) a Threat to New Zealand Natural Grassland
Ecosystems?
AB - Listronotus bonariensis (Argentine stem weevil) is a stem-boring weevil that has
become a major pasture pest in New Zealand, and cool climate turf grass in
Australia. This species is also frequently found in native tussock grassland in
New Zealand. Laboratory and field trials were established to determine the risk
posed to both seedlings and established plants of three native grass species
compared to what happens with a common host of this species, hybrid ryegrass (L.
perenne X L. multiflorum). Adult weevil feeding damage scores were higher on Poa
colensoi and Festuca novae-zelandiae than Chionochloa rigida. Oviposition was
lower on P. colensoi than hybrid ryegrass, and no eggs were laid on F. novae
zelandiae. In field trials using the same four species established as spaced
plants L. bonariensis laid more eggs per tiller in ryegrass in a low altitude
pasture site than in ryegrass in a higher altitude site. No eggs were found on
the three native grass species at the tussock sites, and only low numbers were
found on other grasses at the low altitude pasture site. Despite this, numbers of
adult weevils were extracted from the plants in the field trials. These may have
comprised survivors of the original weevils added to the plants, together with
new generation weevils that had emerged during the experiment. Irrespective,
higher numbers were recovered from the tussock site plants than from those from
the pasture site. It was concluded that L. bonariensis is likely to have little
overall impact, but a greater impact on native grass seedling survival than on
established plants.
PMID- 27507980
TI - Genetic Diversity of Cultivated Lentil (Lens culinaris Medik.) and Its Relation
to the World's Agro-ecological Zones.
AB - Assessment of genetic diversity and population structure of germplasm collections
plays a critical role in supporting conservation and crop genetic enhancement
strategies. We used a cultivated lentil (Lens culinaris Medik.) collection
consisting of 352 accessions originating from 54 diverse countries to estimate
genetic diversity and genetic structure using 1194 polymorphic single nucleotide
polymorphism (SNP) markers which span the lentil genome. Using principal
coordinate analysis, population structure analysis and UPGMA cluster analysis,
the accessions were categorized into three major groups that prominently
reflected geographical origin (world's agro-ecological zones). The three clusters
complemented the origins, pedigrees, and breeding histories of the germplasm. The
three groups were (a) South Asia (sub-tropical savannah), (b) Mediterranean, and
(c) northern temperate. Based on the results from this study, it is also clear
that breeding programs still have considerable genetic diversity to mine within
the cultivated lentil, as surveyed South Asian and Canadian germplasm revealed
narrow genetic diversity.
PMID- 27507981
TI - Why Be a Shrub? A Basic Model and Hypotheses for the Adaptive Values of a Common
Growth Form.
AB - Shrubs are multi-stemmed short woody plants, more widespread than trees,
important in many ecosystems, neglected in ecology compared to herbs and trees,
but currently in focus due to their global expansion. We present a novel model
based on scaling relationships and four hypotheses to explain the adaptive
significance of shrubs, including a review of the literature with a test of one
hypothesis. Our model describes advantages for a small shrub compared to a small
tree with the same above-ground woody volume, based on larger cross-sectional
stem area, larger area of photosynthetic tissue in bark and stem, larger vascular
cambium area, larger epidermis (bark) area, and larger area for sprouting, and
faster production of twigs and canopy. These components form our Hypothesis 1
that predicts higher growth rate for a small shrub than a small tree. This
prediction was supported by available relevant empirical studies (14
publications). Further, a shrub will produce seeds faster than a tree (Hypothesis
2), multiple stems in shrubs insure future survival and growth if one or more
stems die (Hypothesis 3), and three structural traits of short shrub stems
improve survival compared to tall tree stems (Hypothesis 4)-all hypotheses have
some empirical support. Multi-stemmed trees may be distinguished from shrubs by
more upright stems, reducing bending moment. Improved understanding of shrubs can
clarify their recent expansion on savannas, grasslands, and alpine heaths. More
experiments and other empirical studies, followed by more elaborate models, are
needed to understand why the shrub growth form is successful in many habitats.
PMID- 27507982
TI - Molecular Characterization of the 14-3-3 Gene Family in Brachypodium distachyon
L. Reveals High Evolutionary Conservation and Diverse Responses to Abiotic
Stresses.
AB - The 14-3-3 gene family identified in all eukaryotic organisms is involved in a
wide range of biological processes, particularly in resistance to various abiotic
stresses. Here, we performed the first comprehensive study on the molecular
characterization, phylogenetics, and responses to various abiotic stresses of the
14-3-3 gene family in Brachypodium distachyon L. A total of seven 14-3-3 genes
from B. distachyon and 120 from five main lineages among 12 species were
identified, which were divided into five well-conserved subfamilies. The
molecular structure analysis showed that the plant 14-3-3 gene family is highly
evolutionarily conserved, although certain divergence had occurred in different
subfamilies. The duplication event investigation revealed that segmental
duplication seemed to be the predominant form by which the 14-3-3 gene family had
expanded. Moreover, seven critical amino acids were detected, which may
contribute to functional divergence. Expression profiling analysis showed that
BdGF14 genes were abundantly expressed in the roots, but showed low expression in
the meristems. All seven BdGF14 genes showed significant expression changes under
various abiotic stresses, including heavy metal, phytohormone, osmotic, and
temperature stresses, which might play important roles in responses to multiple
abiotic stresses mainly through participating in ABA-dependent signaling and
reactive oxygen species-mediated MAPK cascade signaling pathways. In particular,
BdGF14 genes generally showed upregulated expression in response to multiple
stresses of high temperature, heavy metal, abscisic acid (ABA), and salicylic
acid (SA), but downregulated expression under H2O2, NaCl, and polyethylene glycol
(PEG) stresses. Meanwhile, dynamic transcriptional expression analysis of BdGF14
genes under longer treatments with heavy metals (Cd(2+), Cr(3+), Cu(2+), and
Zn(2+)) and phytohormone (ABA) and recovery revealed two main expression trends
in both roots and leaves: up-down and up-down-up expression from stress
treatments to recovery. This study provides new insights into the structures and
functions of plant 14-3-3 genes.
PMID- 27507983
TI - Validation of Suitable Reference Genes for Assessing Gene Expression of MicroRNAs
in Lonicera japonica.
AB - MicroRNAs (miRNAs), which play crucial regulatory roles in plant secondary
metabolism and responses to the environment, could be developed as promising
biomarkers for different varieties and production areas of herbal medicines.
However, limited information is available for miRNAs from Lonicera japonica,
which is widely used in East Asian countries owing to various pharmaceutically
active secondary metabolites. Selection of suitable reference genes for
quantification of target miRNA expression through quantitative real-time (qRT)
PCR is important for elucidating the molecular mechanisms of secondary metabolic
regulation in different tissues and varieties of L. japonica. For precise
normalization of gene expression data in L. japonica, 16 candidate miRNAs were
examined in three tissues, as well as 21 cultivated varieties collected from 16
production areas, using GeNorm, NormFinder, and RefFinder algorithms. Our results
revealed combination of u534122 and u3868172 as the best reference genes across
all samples. Their specificity was confirmed by detecting the cycling threshold
(C t) value ranges in different varieties of L. japonica collected from diverse
production areas, suggesting the use of these two reference miRNAs is sufficient
for accurate transcript normalization with different tissues, varieties, and
production areas. To our knowledge, this is the first report on validation of
reference miRNAs in honeysuckle (Lonicera spp.). Restuls from this study can
further facilitate discovery of functional regulatory miRNAs in different
varieties of L. japonica.
PMID- 27507984
TI - Crystal Structure Analysis and the Identification of Distinctive Functional
Regions of the Protein Elicitor Mohrip2.
AB - The protein elicitor MoHrip2, which was extracted from Magnaporthe oryzae as an
exocrine protein, triggers the tobacco immune system and enhances blast
resistance in rice. However, the detailed mechanisms by which MoHrip2 acts as an
elicitor remain unclear. Here, we investigated the structure of MoHrip2 to
elucidate its functions based on molecular structure. The three-dimensional
structure of MoHrip2 was obtained. Overall, the crystal structure formed a beta
barrel structure and showed high similarity to the pathogenesis-related (PR)
thaumatin superfamily protein thaumatin-like xylanase inhibitor (TL-XI). To
investigate the functional regions responsible for MoHrip2 elicitor activities,
the full length and eight truncated proteins were expressed in Escherichia coli
and were evaluated for elicitor activity in tobacco. Biological function analysis
showed that MoHrip2 triggered the defense system against Botrytis cinerea in
tobacco. Moreover, only MoHrip2M14 and other fragments containing the 14 amino
acids residues in the middle region of the protein showed the elicitor activity
of inducing a hypersensitive response and resistance related pathways, which were
similar to that of full-length MoHrip2. These results revealed that the central
14 amino acid residues were essential for anti-pathogenic activity.
PMID- 27507985
TI - Raffinose Family Oligosaccharides Act As Galactose Stores in Seeds and Are
Required for Rapid Germination of Arabidopsis in the Dark.
AB - Raffinose synthase 5 (AtRS5, At5g40390) was characterized from Arabidopsis as a
recombinant enzyme. It has a far higher affinity for the substrates galactinol
and sucrose than any other raffinose synthase previously reported. In addition
raffinose synthase 5 is also working as a galactosylhydrolase, degrading
galactinol, and raffinose under certain conditions. Together with raffinose
synthase 4, which is predominantly a stachyose synthase, both enzymes contribute
to the raffinose family oligosaccharide (RFO) accumulation in seeds. A double
knockout in raffinose synthase 4 and raffinose synthase 5 (DeltaAtRS4,5) was
generated, which is devoid of RFOs in seeds. Unstressed leaves of 4 week old
DeltaAtRS4,5 plants showed drastically 23.8-fold increased concentrations of
galactinol. Unexpectedly, raffinose appeared again in drought stressed
DeltaAtRS4,5 plants, but not under other abiotic stress conditions. Drought
stress leads to novel transcripts of raffinose synthase 6 suggesting that this
isoform is a further stress inducible raffinose synthase in Arabidopsis.
DeltaAtRS4,5 seeds showed a 5 days delayed germination phenotype in darkness and
an elevated expression of the transcription factor phytochrome interacting factor
1 (AtPIF1) target gene AtPIF6, being a repressor of germination. This prolonged
dormancy is not seen during germination in the light. Exogenous galactose
partially promotes germination of DeltaAtRS4,5 seeds in the dark suggesting that
RFOs act as a galactose store and repress AtPIF6 transcripts.
PMID- 27507986
TI - Spatial and Temporal Variation in Selection of Genes Associated with Pearl Millet
Varietal Quantitative Traits In situ.
AB - Ongoing global climate changes imply new challenges for agriculture. Whether
plants and crops can adapt to such rapid changes is still a widely debated
question. We previously showed adaptation in the form of earlier flowering in
pearl millet at the scale of a whole country over three decades. However, this
analysis did not deal with variability of year to year selection. To understand
and possibly manage plant and crop adaptation, we need more knowledge of how
selection acts in situ. Is selection gradual, abrupt, and does it vary in space
and over time? In the present study, we tracked the evolution of allele frequency
in two genes associated with pearl millet phenotypic variation in situ. We
sampled 17 populations of cultivated pearl millet over a period of 2 years. We
tracked changes in allele frequencies in these populations by genotyping more
than seven thousand individuals. We demonstrate that several allele frequencies
changes are compatible with selection, by correcting allele frequency changes
associated with genetic drift. We found marked variation in allele frequencies
from year to year, suggesting a variable selection effect in space and over time.
We estimated the strength of selection associated with variations in allele
frequency. Our results suggest that the polymorphism maintained at the genes we
studied is partially explained by the spatial and temporal variability of
selection. In response to environmental changes, traditional pearl millet
varieties could rapidly adapt thanks to this available functional variability.
PMID- 27507987
TI - Genetic Diversity and Molecular Evolution of a Violaxanthin De-epoxidase Gene in
Maize.
AB - Violaxanthin de-epoxidase (VDE) has a critical role in the carotenoid
biosynthesis pathway, which is involved in protecting the photosynthesis
apparatus from damage caused by excessive light. Here, a VDE gene in maize,
ZmVDE1, was cloned and shown to have functional domains in common with the
gramineous VDE protein. Candidate gene association analysis indicated that no
polymorphic sites in ZmVDE1 were significant association with any of the examined
carotenoid-related traits at P = 0.05 in an association panel containing 155
maize inbred lines. Nucleotide diversity analysis of VDE1 in maize and teosinte
indicated that its exon had less genetic variation, consistent with the conserved
function of VDE1 in plants. In addition, dramatically reduced nucleotide
diversity, fewer haplotypes and a significantly negative parameter deviation for
Tajima's D test of ZmVDE1 in maize and teosinte suggested that a potential
selective force had acted across the ZmVDE1 locus. We further identified a 4.2 Mb
selective sweep with low recombination surrounding the ZmVDE1 locus that resulted
in severely reduced nucleotide diversity on chromosome 2. Collectively, natural
selection and the conserved domains of ZmVDE1 might show an important role in the
xanthophyll cycle of the carotenoid biosynthesis pathway.
PMID- 27507989
TI - Comparative Efficacy of Topical Curcumin and Triamcinolone for Oral Lichen
Planus: A Randomized, Controlled Clinical Trial.
AB - OBJECTIVES: Lichen planus (LP) is a chronic inflammatory mucocutaneous disease.
Its treatment is often symptomatic and includes topical and systemic
corticosteroids. Although corticosteroid therapy is usually successful, it has
side effects and thus, an alternative treatment is favorable. The aim of this
study was to compare the efficacy of topical curcumin and triamcinolone for
treatment of oral lichen planus (OLP). MATERIALS AND METHODS: In this study, 50
patients (36 women and 14 men) in the age range of 38 to 73 years with OLP were
randomly divided into two groups. Each group received 0.1% triamcinolone or 5%
curcumin oral paste three times a day for four weeks. Assessment of the
appearance score and severity of pain was done at baseline and at the end of two
and four weeks and recorded in the patients' questionnaires. The data were
analyzed by SPSS 17 software, using the Mann-Whitney and Spearman's tests.
RESULTS: With respect to pain reduction, nine patients (36%) in the curcumin
group and eight patients (32%) in the triamcinolone group showed complete
remission. With respect to the appearance score, one patient (4%) in each group
showed complete remission. No statistically significant difference was noted
between the two groups. CONCLUSION: Application of curcumin is suggested for
treatment of OLP because of its desirable anti-inflammatory effects and
insignificant side effects.
PMID- 27507988
TI - Spatial Genome Organization and Its Emerging Role as a Potential Diagnosis Tool.
AB - In eukaryotic cells the genome is highly spatially organized. Functional
relevance of higher order genome organization is implied by the fact that
specific genes, and even whole chromosomes, alter spatial position in concert
with functional changes within the nucleus, for example with modifications to
chromatin or transcription. The exact molecular pathways that regulate spatial
genome organization and the full implication to the cell of such an organization
remain to be determined. However, there is a growing realization that the spatial
organization of the genome can be used as a marker of disease. While global
genome organization patterns remain largely conserved in disease, some genes and
chromosomes occupy distinct nuclear positions in diseased cells compared to their
normal counterparts, with the patterns of reorganization differing between
diseases. Importantly, mapping the spatial positioning patterns of specific
genomic loci can distinguish cancerous tissue from benign with high accuracy.
Genome positioning is an attractive novel biomarker since additional quantitative
biomarkers are urgently required in many cancer types. Current diagnostic
techniques are often subjective and generally lack the ability to identify
aggressive cancer from indolent, which can lead to over- or under-treatment of
patients. Proof-of-principle for the use of genome positioning as a diagnostic
tool has been provided based on small scale retrospective studies. Future large
scale studies are required to assess the feasibility of bringing spatial genome
organization-based diagnostics to the clinical setting and to determine if the
positioning patterns of specific loci can be useful biomarkers for cancer
prognosis. Since spatial reorganization of the genome has been identified in
multiple human diseases, it is likely that spatial genome positioning patterns as
a diagnostic biomarker may be applied to many diseases.
PMID- 27507990
TI - Accuracy of Cone Beam Computed Tomography, Photostimulable Phosphor Plate Digital
Radiography and Conventional Radiography for Detection of Artificial Cancellous
Bone Defects.
AB - OBJECTIVES: The optimal goal of radiography is to provide high-quality diagnostic
images with the least patient radiation dose. The aim of this study was to
evaluate the accuracy of cone-beam computed tomography (CBCT) and intraoral
photostimulable phosphor plate (PSP) digital and film-based conventional
radiography for detection of artificial cancellous bone defects. MATERIALS AND
METHODS: Five dry human mandibles were used in this study. The mandibles were
placed inside a water bath made of plexiglass plates; then PSP and CBCT scans
were obtained. The mandibles were cut by a coping saw in buccolingual dimension
and oval defects measuring 6.1*6.1 mm, 3*6.1 mm and 4*4 mm were created by a
milling machine in the spongy bone. After fixing the two parts together (buccal
and lingual), radiographs were repeated. Presence or absence of defects on images
was evaluated and recorded by the two observers. Using SPSS 16, compatibility
level, sensitivity, specificity and receiver operating curve (ROC) analysis were
determined for each observer. RESULTS: The intraobserver agreement in all three
imaging modalities was low to moderate (kappa<=0.613). The inter-observer
agreement in all the three imaging modalities was moderate (kappa=0.406). The
area under the curve (AUC) of the imaging modalities in each observation was not
significantly different. The area under the curve based on defect size for the
two observers was not significantly different either. CONCLUSION: Defects
confined to spongy bone can be identified on film and PSP radiographs and CBCT
scans. However, interpretation of PSP images and CBCT scans needs greater
expertise and skills.
PMID- 27507991
TI - Effect of a Desensitizing Varnish on Microleakage of Two Self-Etch Adhesives.
AB - OBJECTIVES: The aim of this in-vitro experimental study was to assess the effect
of application of a desensitizing varnish on the enamel and dentin marginal seal.
MATERIALS AND METHODS: Seventy-two freshly extracted, intact human premolar teeth
were divided into four groups (n=18). Class V cavities (3mm in length, 2mm in
width and 2mm in depth) were prepared on the buccal surface of each tooth. The
following sealing materials were applied in the four groups: One-step Clearfil S3
Bond (S3) self-etch adhesive, two-step Clearfil SE Bond (SE) self-etch adhesive,
S3 Bond+ VivaSens desensitizing varnish (VS+S3) and Clearfil SE Bond + VivaSens
(VS+SE). The cavities on the teeth were then incrementally filled with Z350 light
cure composite. The teeth were stored in distilled water for 24 hours at 37
degrees C, and were then thermocycled for 1000 cycles. Then, all the specimens
were prepared for dye penetration test and were immersed in 2% basic fuchsin dye
and incubated at 37 degrees C for 24 hours. The teeth were then sectioned
buccolingually along the center of restorations with a diamond disk. Microleakage
at the tooth-restoration interface was assessed in the enamel and dentin margins
blindly using dye penetration under a stereomicroscope at *20 magnification.
RESULTS: There was significantly greater leakage at the enamel and dentin margins
in group VS+SE than in group SE; also, these values were higher in group VS+S3
than in S3. CONCLUSION: Combined application of desensitizing varnish and self
etch adhesives seems to increase microleakage in composite restorations. Thus,
its application is not suggested.
PMID- 27507992
TI - In Vitro Effect of Porcelain Firing Cycle and Different Thicknesses of IPS E.max
CAD Core on Marginal Accuracy of All-Ceramic Restorations.
AB - OBJECTIVES: Marginal adaptation is important for long-term success of full
coverage restorations. The aim of this study was to determine the effect of
porcelain firing cycle and different thicknesses of IPS e.max core on marginal
accuracy of all-ceramic restorations. MATERIALS AND METHODS: A standard stainless
steel die with 0.8 mm classic chamfer finish line and 10 degrees taper was used
in this in vitro study. An impression was taken from the stainless steel die to
fabricate 20 epoxy resin dies, which were then scanned and IPS e.max CAD cores
were fabricated using computer-aided design/computer-aided manufacturing
(CAD/CAM) technique in two groups of 10 with 0.7 mm (group A) and 0.4mm (group B)
core thickness. Copings were then placed on their respective dies and randomly
numbered. The amount of marginal gap was measured in 10 points under a
stereomicroscope (*90 magnification) before and after porcelain veneering.
RESULTS: The mean gap in 0.7mm and 0.4mm core thicknesses was 15.62+/-2.55MUm and
19.68+/-3.09MUm before porcelain firing and 32.01+/-3.19MUm and 35.24+/-3.8MUm
after porcelain firing. The difference in marginal gap between the two
thicknesses was significant before porcelain firing but not significant after
veneering. Significant differences were also found in the marginal gap before and
after porcelain veneering in each group. CONCLUSION: The porcelain firing cycle
increases marginal gap in IPS e.max CAD restorations; 0.3 mm decrease in core
thickness slightly increased marginal discrepancy, however it was not
significant.
PMID- 27507993
TI - Regenerative Effects of Three Types of Allografts on Rabbit Calvarium: An Animal
Study.
AB - OBJECTIVES: The aim of this study was to histologically compare the regenerative
properties of two allografts manufactured by two Iranian companies. MATERIALS AND
METHODS: In this study, four 8-mm defects were produced in the calvaria of 12
rabbits. In three defects, three types of allografts namely ITB, CenoBone and
Grafton were placed and one defect served as control. Samples were prepared and
histomorphometric evaluations were carried out after healing periods of four
weeks (interval 1) and eight weeks (interval 2). Qualitative and quantities
variables were compared and analyzed with SPSS software. RESULTS: Mild
inflammation was observed in 45% and 12.5% of the samples in the first and second
intervals, respectively. Foreign body reaction was observed in only 5% of the
samples. The quality of regenerated bone was immature, mixed and lamellar in
54.5%, 15.9% and 4.5% of the samples, respectively. The rate of allograft
resorption was the highest and lowest in the CenoBone and Grafton samples,
respectively. The mean amount of regenerated bone was higher in areas containing
Grafton; however, the differences were not statistically significant. CONCLUSION:
Despite the differences in the numerical values of bone regeneration, there were
no statistically significant differences in bone generation among the material
groups, and allografts manufactured in Iran can be suitable alternatives to
Grafton with the same good properties. Further studies are necessary to clarify
the efficacy of these allografts.
PMID- 27507994
TI - Assessment of IgG Antibodies Against HSV1, HSV2, CMV and EBV in Patients with
Pemphigus Vulgaris Versus Healthy People.
AB - OBJECTIVES: Regarding the implication of viruses particularly herpes in pemphigus
vulgaris, we sought to assess and compare the level of immunoglobulin G (IgG)
antibodies against herpes simplex virus types 1 and 2 (HSV1 and HSV2),
cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with pemphigus
vulgaris and healthy people. MATERIALS AND METHODS: In this cross-sectional
study, 25 patients with pemphigus vulgaris and 27 healthy individuals comprised
the experimental and control groups, respectively. Serum samples were taken from
both groups; the levels of IgG antibodies against HSV1, HSV2, CMV and EBV were
measured using ELISA. RESULTS: Immunoglobulin G titer was higher for all four
viruses in the patient group in comparison to the control group. This difference
was significant for anti-EBV (P= 0.005), anti-CMV (P=0.0001) and anti-HSV2
(P=0.001) but not significant for anti-HSV1 (P= 0.36). CONCLUSION: Viruses
including EBV, CMV, and HSV2 probably play a role in the pathogenesis of
pemphigus in addition to the effects of genetics, toxins and other predisposing
factors. In this study, no statistically significant relationship was observed
between HSV1 and pemphigus vulgaris, which was probably due to the high titer of
anti-HSV1 IgG in healthy individuals in the community. More studies must be done
in this regard.
PMID- 27507995
TI - Comparison of Apical Sealing Ability of Two Phases of Gutta-Percha: A Bacterial
Leakage Model.
AB - OBJECTIVES: The aim of this study was to compare apical sealing ability of alpha
and beta phases of gutta-percha by means of bacterial leakage model. MATERIALS
AND METHODS: Fifty single-rooted human premolars were selected. The root canals
were prepared with Mtwo rotary instruments up to apical #35.04. Forty teeth were
randomly divided into two groups (n= 20). The root canals were obturated by alpha
phase (G1) and beta phase (G2) of gutta-percha and AH26 sealer, respectively,
with warm vertical compaction technique. Ten teeth served as positive (n=8) and
negative (n=2) control groups. Then, the specimens were sterilized with ethylene
oxide gas. Bacterial suspension of Enterococcus faecalis (E. faecalis) in 0.5
McFarland concentration was prepared. All teeth were mounted in plastic vial caps
containing Muller Hinton broth and then exposed to bacterial suspension of E.
faecalis every three days up to 31 days. The number of days required for the
contamination of the entire root canals was recorded. The data were analyzed
using Mann Whitney U test. RESULTS: There were no significant differences in
bacterial leakage between the G1 and G2 groups (P>0.05). Negative controls
revealed no microbial leakage; whereas positive controls showed gross microbial
leakage. CONCLUSION: Despite better thermal conduction and adaptability of alpha
phase of guttapercha, our study revealed no significant difference in bacterial
leakage between alpha and beta phases of gutta-percha in warm vertical
compaction.
PMID- 27507996
TI - Immunohistochemical Evaluation of Angiogenesis and Cell Proliferation in Tongue
Squamous Cell Carcinoma.
AB - OBJECTIVES: Squamous cell carcinoma (SCC) is the most common malignant neoplasm
of the oral cavity and a public health threat. Tumor progression is believed to
be influenced by angiogenesis as well as tumor cell proliferation; however, the
correlation of these two factors in tongue SCC still remains unclear. This study
aimed to assess the correlation of these two factors in tongue SCC. MATERIALS AND
METHODS: Twenty-four paraffin block sections of tongue SCC were stained with
monoclonal antibodies against CD105 and Ki-67. In order to assess the expressions
of CD105 and Ki-67 to evaluate CD105 microvessel density (MVD), positively
stained microvessels were counted in a predominantly vascular area (hot spot) in
each specimen at *400 magnification. The proliferation index was expressed as a
percentage of Ki-67 positive cells. Data were analyzed by t-test and Pearson's
correlation coefficient (P<0.05). RESULTS: The CD105 MVD was related to
histological grading as well as Ki67 labeling index (LI; P= 0.045 and P=0.047,
respectively). Both CD105 MVD and KI67 LI were unrelated to sex (P=0.41 and
P=0.78, respectively) and age (P=0.20 and P=0.36, respectively) of the patients.
No correlation was found between CD105 MVD and Ki67 LI (P=0.86). CONCLUSION: The
mean CD105 MVD was significantly lower in poorly differentiated tumors. This
finding suggests that CD105 MVD may serve as a valuable prognostic factor in
tongue SCC. Absence of correlation between MVD and tumor cell proliferation
indicates that these processes may be guided by unrelated mechanisms.
PMID- 27507997
TI - Effects of Different Viewing Conditions on Radiographic Interpretation.
AB - OBJECTIVES: Optimum viewing conditions facilitate identification of radiographic
details and decrease the need for retakes, patients' costs and radiation dose.
This study sought to evaluate the effects of different viewing conditions on
radiographic interpretation. MATERIALS AND METHODS: This diagnostic study was
performed by evaluating radiograph of a 7mm-thick aluminum block, in which 10
holes with 2mm diameters were randomly drilled with depths ranging from 0.05 mm
to 0.50mm. The radiograph was viewed by four oral radiologists independently
under four viewing conditions, including a white light viewing light box in a lit
room, yellow light viewing light box in a lit room, white light viewing light box
in a dark room and yellow light viewing light box in a dark room. Number of
circular shadows observed on the film was recorded. The data were analyzed by two
way ANOVA. RESULTS: The mean number of detected circular shadows was 6.75, 7.5,
7.25 and 7.75 in white light viewing light box in a lit room, white light viewing
light box in a dark room, yellow light viewing light box in a lit room and yellow
light viewing light box in a dark room, respectively. Although the surrounding
illumination had statistically significant effect on the radiographic details
(P<=0.03), the light color of the viewing light box had no significant effect on
visibility of the radiographic details. CONCLUSION: White and yellow light of the
viewing light box had no significant effect on visibility of the radiographic
details but more information was obtained in a dark room.
PMID- 27507998
TI - Effect of Bonding Application Time on Bond Strength of Composite Resin to Glass
Ionomer Cement.
AB - OBJECTIVES: This experimental study evaluated the effect of bonding application
time on the microshear bond strength of composite resin to different types of
glass ionomer cements (GICs). MATERIALS AND METHODS: One-hundred and sixty
specimens (two conventional and two resin-modified GICs) were prepared and
divided into 16 groups. The surface of all specimens was prepared using two
different bonding systems (Frog and Stea) at three different times. After
setting, the composite resin (Z100) was placed over the GICs. The specimens were
then stored in distilled water for 24 hours (37 degrees C) and exposed to
microshear stresses at a crosshead speed of 1 mm/min. The results were analyzed
using three-way ANOVA and Tukey's test (P<0.05). RESULTS: In conventional GICs,
bond strength was affected by the type of bonding system at different times, and
bond strength was significantly higher in the Fuji II group compared to Riva Self
Cure group. In the Riva Self Cure group, bond strength was significantly affected
by time; whereas, the type of bonding system failed to exert a significant effect
on bond strength. There was no significant correlation between the type of
bonding system and the two brands of resin-modified GICs. Bond strength was not
affected by the type of bonding agent; however, among the two brands of resin
modified GICs, Fuji II LC yielded a significantly stronger bond. CONCLUSION: It
appears that the type of bonding agent does not affect the microshear bond
strength, and the bonding application time affects the microshear bond strength
in Riva Self Cure GICs.
PMID- 27507999
TI - Passive acoustic monitoring reveals group ranging and territory use: a case study
of wild chimpanzees (Pan troglodytes).
AB - BACKGROUND: Assessing the range and territories of wild mammals traditionally
requires years of data collection and often involves directly following
individuals or using tracking devices. Indirect and non-invasive methods of
monitoring wildlife have therefore emerged as attractive alternatives due to
their ability to collect data at large spatiotemporal scales using standardized
remote sensing technologies. Here, we investigate the use of two novel passive
acoustic monitoring (PAM) systems used to capture long-distance sounds produced
by the same species, wild chimpanzees (Pan troglodytes), living in two different
habitats: forest (Tai, Cote d'Ivoire) and savanna-woodland (Issa valley,
Tanzania). RESULTS: Using data collected independently at two field sites, we
show that detections of chimpanzee sounds on autonomous recording devices were
predicted by direct and indirect indices of chimpanzee presence. At Tai, the
number of chimpanzee buttress drums detected on recording devices was positively
influenced by the number of hours chimpanzees were seen ranging within a 1 km
radius of a device. We observed a similar but weaker relationship within a 500 m
radius. At Issa, the number of indirect chimpanzee observations positively
predicted detections of chimpanzee loud calls on a recording device within a 500
m but not a 1 km radius. Moreover, using just seven months of PAM data, we could
locate two known chimpanzee communities in Tai and observed monthly spatial
variation in the center of activity for each group. CONCLUSIONS: Our work shows
PAM is a promising new tool for gathering information about the ranging behavior
and habitat use of chimpanzees and can be easily adopted for other large
territorial mammals, provided they produce long-distance acoustic signals that
can be captured by autonomous recording devices (e.g., lions and wolves). With
this study we hope to promote more interdisciplinary research in PAM to help
overcome its challenges, particularly in data processing, to improve its wider
application.
PMID- 27508000
TI - Precipitating factors and targeted therapies in combating the perils of sickle
cell disease--- A special nutritional consideration.
AB - Nutritional research in sickle cell disease has been the focus in recent times
owing to not only specific nutritional deficiencies, but also the improvements
associated with less painful episodes. Though hydroxyurea remains the drug of
choice, certain adverse health effects on long term supplementation makes room
for researches of different compounds. Macro and micro nutrient deficiencies,
along with vitamins, play an important role in not only meeting the calorific
needs, but also reducing clinical complications and growth abnormalities.
Symptoms of hyper protein metabolism, increased cell turnover, increased cardiac
output, and appetite suppression due to enhanced cytokine production, might give
us leads for better understanding of the mechanisms involved. Different
nutritional approaches comprising of traditional herbal therapies, antioxidants,
flavonoids, vitamins, minerals etc., reducing oxidative stress and blood
aggregation, have been tried out to increase the health potential. Nutritional
therapies may also serve complementary to the newer therapies using ozone,
hematopoietic stem cell transplantation, antifungal medications, erythropoietin
etc. Herein we try to present a holistic picture of the different patho
physiological mechanisms, and nutritional strategies adopted.
PMID- 27508001
TI - Relationship of suicide rates with climate and economic variables in Europe
during 2000-2012.
AB - BACKGROUND: It is well known that suicidal rates vary considerably among European
countries and the reasons for this are unknown, although several theories have
been proposed. The effect of economic variables has been extensively studied but
not that of climate. METHODS: Data from 29 European countries covering the years
2000-2012 and concerning male and female standardized suicidal rates (according
to WHO), economic variables (according World Bank) and climate variables were
gathered. The statistical analysis included cluster and principal component
analysis and categorical regression. RESULTS: The derived models explained 62.4 %
of the variability of male suicidal rates. Economic variables alone explained
26.9 % and climate variables 37.6 %. For females, the respective figures were
41.7, 11.5 and 28.1 %. Male suicides correlated with high unemployment rate in
the frame of high growth rate and high inflation and low GDP per capita, while
female suicides correlated negatively with inflation. Both male and female
suicides correlated with low temperature. DISCUSSION: The current study reports
that the climatic effect (cold climate) is stronger than the economic one, but
both are present. It seems that in Europe suicidality follows the
climate/temperature cline which interestingly is not from south to north but from
south to north-east. This raises concerns that climate change could lead to an
increase in suicide rates. The current study is essentially the first successful
attempt to explain the differences across countries in Europe; however, it is an
observational analysis based on aggregate data and thus there is a lack of
control for confounders.
PMID- 27508002
TI - Pattern and predictors of mortality in necrotizing fasciitis patients in a single
tertiary hospital.
AB - BACKGROUND: Necrotizing fasciitis (NF) is a fatal aggressive infectious disease.
We aimed to assess the major contributing factors of mortality in NF patients.
METHODS: A retrospective study was conducted at a single surgical intensive care
unit between 2000 and 2013. Patients were categorized into 2 groups based on
their in-hospital outcome (survivors versus non-survivors). RESULTS: During a14
year period, 331 NF patients were admitted with a mean age of 50.8 +/- 15.4 years
and 74 % of them were males Non-survivors (26 %) were 14.5 years older (p =
0.001) and had lower frequency of pain (p = 0.01) and fever (p = 0.001) than
survivors (74 %) at hospital presentation. Diabetes mellitus, hypertension, and
coronary artery disease were more prevalent among non-survivors (p = 0.001). The
2 groups were comparable for the site of infection; except for sacral region that
was more involved in non-survivors (p = 0.005). On admission, non-survivors had
lower hemoglobin levels (p = 0.001), platelet count (p = 0.02), blood glucose
levels (p = 0.07) and had higher serum creatinine (p = 0.001). Non-survivors had
greater median LRINEC (Laboratory Risk Indicator for NECrotizing fasciitis score)
and Sequential Organ Failure Assessment (SOFA) scores (p = 0.001). Polybacterial
and monobacterial gram negative infections were more evident in non-survivors
group. Monobacterial pseudomonas (p = 0.01) and proteus infections (p = 0.005)
were reported more among non-survivors. The overall mortality was 26 % and the
major causes of death were bacteremia, septic shock and multiorgan failure.
Multivariate analysis showed that age and SOFA score were independent predictors
of mortality in the entire study population. CONCLUSION: The mortality rate is
quite high as one quarter of NF patients died during hospitalization. The present
study highlights the clinical and laboratory characteristics and predictors of
mortality in NF patients.
PMID- 27508003
TI - Mapping N-linked glycosylation of carbohydrate-active enzymes in the secretome of
Aspergillus nidulans grown on lignocellulose.
AB - BACKGROUND: The genus Aspergillus includes microorganisms that naturally degrade
lignocellulosic biomass, secreting large amounts of carbohydrate-active enzymes
(CAZymes) that characterize their saprophyte lifestyle. Aspergillus has the
capacity to perform post-translational modifications (PTM), which provides an
additional advantage for the use of these organisms as a host for the production
of heterologous proteins. In this study, the N-linked glycosylation of CAZymes
identified in the secretome of Aspergillus nidulans grown on lignocellulose was
mapped. RESULTS: Aspergillus nidulans was grown in glucose, xylan and pretreated
sugarcane bagasse (SCB) for 96 h, after which glycoproteomics and glycomics were
carried out on the extracellular proteins (secretome). A total of 265 proteins
were identified, with 153, 210 and 182 proteins in the glucose, xylan and SCB
substrates, respectively. CAZymes corresponded to more than 50 % of the total
secretome in xylan and SCB. A total of 182 N-glycosylation sites were identified,
of which 121 were detected in 67 CAZymes. A prevalence of the N-glyc sequon N-X-T
(72.2 %) was observed in N-glyc sites compared with N-X-S (27.8 %). The amino
acids flanking the validated N-glyc sites were mainly composed of hydrophobic and
polar uncharged amino acids. Selected proteins were evaluated for conservation of
the N-glyc sites in Aspergilli homologous proteins, but a pattern of conservation
was not observed. A global analysis of N-glycans released from the proteins
secreted by A. nidulans was also performed. While the proportion of N-glycans
with Hex5 to Hex9 was similar in the xylan condition, a prevalence of Hex5 was
observed in the SCB and glucose conditions. CONCLUSIONS: The most common and
frequent N-glycosylated motifs, an overview of the N-glycosylation of the CAZymes
and the number of mannoses found in N-glycans were analyzed. There are many
bottlenecks in protein production by filamentous fungi, such as folding,
transport by vesicles and secretion, but N-glycosylation in the correct context
is a fundamental event for defining the high levels of secretion of target
proteins. A comprehensive analysis of the protein glycosylation processes in A.
nidulans will assist with a better understanding of glycoprotein structures,
profiles, activities and functions. This knowledge can help in the optimization
of heterologous expression and protein secretion in the fungal host.
PMID- 27508004
TI - Identification of small marker chromosomes using microarray comparative genomic
hybridization and multicolor fluorescent in situ hybridization.
AB - BACKGROUND: Marker chromosomes are small supernumerary chromosomes that cannot be
unambiguously identified by chromosome banding techniques alone. However, the
precise characterization of marker chromosomes is important for prenatal
diagnosis and proper genetic counseling. In this study, we evaluated the
chromosomal origin of marker chromosomes using a combination of banding
cytogenetics and molecular cytogenetic techniques including diverse fluorescence
in situ hybridization (FISH) assays and array comparative genomic hybridization
(array CGH). RESULTS: In a series of 2871 patients for whom cytogenetic analysis
was requested, 14 cases with small supernumerary marker chromosomes (sSMCs) were
identified. Nine sSMCs were mosaic, and five nonmosaic. Of the nine cases with
known parental origins, four were identified as de novo, and four and one were
maternally and paternally inherited, respectively. Six sSMCs were identified by
FISH using centromeric probes; three sSMCs were derived from chromosome 15,
including two heterochromatic sSMC(15)s and a large sSMC(15) spanning
15q11.1q13.1, and three sSMCs originated from chromosome 14 or 22. Array CGH
revealed two cases with derivatives of chromosome 2 and whole chromosome painting
multicolor-FISH (M-FISH) identified three cases with derivatives of chromosome 6,
16, and 19, respectively. One maker chromosome in Turner syndrome was
characterized as sSMC(X) by preferential application of a centromeric probe for X
chromosome. In addition, one sSMC composed of genomic materials from chromosomes
12 and 18 was identified in parallel with parental karyotype analysis that
revealed the reciprocal balanced translocation. CONCLUSIONS: This report is the
largest study on sSMCs in Korea and expands the spectrum of sSMCs that are
molecularly characterized.
PMID- 27508005
TI - Sex chromosome loss after allogeneic hematopoietic stem cell transplant in
patients with hematologic neoplasms: a diagnostic dilemma for clinical
cytogeneticists.
AB - BACKGROUND: Sex chromosome loss (SCL), including loss of an X chromosome (-X) in
females and loss of the Y chromosome (-Y) in males, resulting in a karyotype of
45,X, rarely occurs in patients post an allogeneic hematopoietic stem cell
transplant (alloHSCT). However, origin of this abnormal clone and its clinical
significance remains unknown. RESULTS: We present 12 cases with SCL who underwent
alloHSCT; 9 patients (4 men and 5 women with a median age of 56 years) developed
isolated SCL after alloHSCT (Group I), and 3 patients (all women with a median
age of 58 years) had a SCL before undergoing alloHSCT after which SCL disappeared
(Group II). The primary neoplasms included chronic lymphocytic leukemia (n = 5),
acute myeloid leukemia (n = 5), chronic myelogenous leukemia with nodal marginal
zone lymphoma (n = 1) and Hodgkin lymphoma (n = 1). According to the
donor/recipient relationship, their alloHSCT can be divided into sex-matched, HLA
matched, unrelated donors (n = 2); sex-mismatched, HLA-matched, unrelated donors
(n = 4); sex-mismatched, HLA-matched, related donors (2 HLA-identical and 2 HLA
haploidentical cases) and sex-matched, HLA-matched, related donors (2 HLA
haploidentical cases). In Group I, isolated SCL was first detected with a median
interval of 3 months (range 1 to 42 months) after the alloHSCT. By the end of
clinical follow-up in patients in Group I, 7 patients expired with a median
overall survival of 45 months (range 3 to 108 months) after alloHSCT and 33
months (range 0 to 66 months) after SCL detection. In Group II, 1 patient expired
with a survival time of 54 months after the alloHSCT. Detection of SCL after
alloHSCT can be transient, intermittent or persistent. CONCLUSIONS:
Interpretation of SCL is challenging in the context of alloHSCT. Chimerism
testing is useful in determining the origin of SCL. In the case of SCL with
donor/recipient chimerism, deduction of the SCL origin by all means and use of "
?X" or "-?Y" in the ISCN nomenclature are recommended. Clinical follow-up with
closely monitoring the SCL by both cytogenetic and molecular analyses is needed.
PMID- 27508006
TI - Evaluation, intervention, and follow-up of patients with diabetes in a primary
health care setting in Brazil: the importance of a specialized mobile
consultancy.
AB - BACKGROUND: Studies show that educational interventions improve glycemic control
in patients with diabetes mellitus (DM), reducing the occurrence of complications
associated with the disease. OBJECTIVES: To evaluate the effects of a mobile DM
consultancy on clinical and laboratory parameters, disease knowledge, and quality
of life in patients with type 2 DM (T2DM) at a primary health care network in
Brazil. METHODS: Randomized clinical trial conducted in a city in southern Brazil
with 52 patients with T2DM receiving care at a primary health care setting. The
intervention lasted for 6 months and consisted of a follow-up with an
endocrinologist (five meetings), treatment adjustment based on clinical
evaluation and laboratory tests, and educational activities with conversation
maps in DM. The statistical analysis included comparison and association tests,
considering p values <=0.05 as statistically significant. RESULTS: The mean age
of the patients was 63.8 years. Most participants were female (63.5 %), had low
educational level (59.6 %) and family history of T2DM (71.2 %), used only oral
hypoglycemic agents to manage their DM (73.2 %), presented unfavorable
anthropometric and laboratory parameters, a high or medium risk of complications
(84.6 %), and inadequate glycemic control (67.3 %; with 71 % of the high-risk
patients presenting a HbA1c level >9 %). Adjustment in pharmacological treatment
was required in 63.5 % of the patients. After the intervention, we observed a
significant 0.46 % decrease in mean HbA1c level (p = 0.0218), particularly among
individuals with inadequate glycemic control (0.71 %; p = 0.0136). Additionally,
there was an increase in disease knowledge scores and a significant decrease in
mean body mass index, waist circumference, and disease impact scores. CONCLUSION:
The intervention improved glycemic control and disease knowledge, reduced the
values of body mass index and waist circumference, and the impact of the disease
on patients' lives. This indicates that care and educational measures improve the
experience of the patients with DM and control of the disease.
PMID- 27508007
TI - Pedigree based DNA sequencing pipeline for germline genomes of cancer families.
AB - BACKGROUND: In the course of our whole-genome sequencing efforts, we have
developed a pipeline for analyzing germline genomes from Mendelian types of
cancer pedigrees (familial cancer variant prioritization pipeline, FCVPP).
RESULTS: The variant calling step distinguishes two types of genomic variants:
single nucleotide variants (SNVs) and indels, which undergo technical quality
control. Mendelian types of variants are assumed to be rare and variants with
frequencies higher that 0.1 % are screened out using human 1000 Genomes (Phase 3)
and non-TCGA ExAC population data. Segregation in the pedigree allows variants to
be present in affected family members and not in old, unaffected ones. The
effectiveness of variant segregation depends on the number and relatedness of the
family members: if over 5 third-degree (or more distant) relatives are available,
the experience has shown that the number of likely variants is reduced from many
hundreds to a few tens. These are then subjected to bioinformatics analysis,
starting with the combined annotation dependent depletion (CADD) tool, which
predicts the likelihood of the variant being deleterious. Different sets of
individual tools are used for further evaluation of the deleteriousness of coding
variants, 5' and 3' untranslated regions (UTRs), and intergenic variants.
CONLUSIONS: The likelihood of success of the present genomic pipeline in finding
novel high- or medium-penetrant genes depends on many steps but first and
foremost, the pedigree needs to be reasonably large and the assignments and
diagnoses among the members need to be correct.
PMID- 27508009
TI - SRT1720, a SIRT1 specific activator, protected H2O2-induced senescent
endothelium.
AB - Silent information regulator 1 (SIRT1) plays a critical role in maintaining
vascular homeostasis via modulating senescent-related signal pathway, however,
the molecular mechanism remains modest clarified. The purpose of this study was
to examine whether SIRT1 specific activator SRT1720 would exhibit pro-angiogenic
and anti-aging properties in response to hydrogen peroxide (H2O2)-induced
endothelial senescence, and determine the underlying mechanisms. We pre-treated
senescent human umbilical vein endothelial cells (HUVECs) with SRT1720,
senescence-associated beta-galactosidase activity, apoptosis, migration, tube
formation, proliferation and angiogenic factors were quantitatively examined. The
results revealed that pharmacologic activation of SIRT1 by SRT1720 rescued
apoptotic HUVECs and upregulated angiogenic response through reinforcing the
protein expressions of angiogenic and survival factors in vitro. Furthermore, we
confirmed that the expressions of endothelial nitric oxide synthase (eNOS),
vascular endothelial growth factor (VEGF) and phosphoryl-Akt were augmented in
SRT1720-treated senescent HUVECs. In conclusion, our data indicated that SRT1720
could protect against endothelial senescence and maintain cell function via
Akt/eNOS/VEGF axis.
PMID- 27508008
TI - Research progress of cardioprotective agents for prevention of anthracycline
cardiotoxicity.
AB - Anthracyclines, including doxorubicin, epirubicin, daunorubicin and aclarubicin,
are widely used as chemotherapeutic agents in the treatment of hematologic and
solid tumor, including acute leukemia, lymphoma, breast cancer, gastric cancer,
soft tissue sarcomas and ovarian cancer. In the cancer treatment, anthracyclines
also can be combined with other chemotherapies and molecular-targeted drugs. The
combination of anthracyclines with other therapies is usually the first-line
treatment. Anthracyclines are effective and potent agents with a broad antitumor
spectrum, but may cause adverse reactions, including hair loss, myelotoxicity, as
well as cardiotoxicity. We used hematopoietic stimulating factors to control the
myelotoxicity, such as G-CSF, EPO and TPO. However, the cardiotoxicity is the
most serious side effect of anthracyclines. Clinical research and practical
observations indicated that the cardiotoxicity of anthracyclines is commonly
progressive and irreversible. Especially to those patients who have the first
time use of anthracyclines, the damage is common. Therefore, early detection and
prevention of anthracyclines induced cardiotoxicity are particularly important
and has already aroused more attention in clinic. By literature review, we
reviewed the research progress of cardioprotective agents for prevention of
anthracycline cardiotoxicity.
PMID- 27508010
TI - Preliminary study of urine metabolism in type two diabetic patients based on GC
MS.
AB - OBJECTIVE: Comparative study of type 2 diabetes and healthy controls by
metabolomics methods to explore the pathogenesis of Type II diabetes. METHODS:
Gas chromatography - mass spectrometry (GC-MS) with a variety of multivariate
statistical analysis methods to the healthy control group 58 cases, 68 cases of
Type II diabetes group were analyzed. Chromatographic conditions: DB-5MS column;
the carrier gas He; flow rate of 1 mL.min(-1), the injection volume 1 uL; split
ratio is 100: 1. MS conditions: electron impact (EI) ion source, an auxiliary
temperature of 280 degrees C, the ion source 230 degrees C, quadrupole 150
degrees C; mass scan range 30~600 mAu. RESULTS: Established analytical method
based on urine metabolomics GC-MS of Type II diabetes, determine the urine
succinic acid, L-leucine, L-isoleucine, tyrosine, slanine, acetoace acid,
mannose, L-isoleucine, L-threonine, Phenylalanine, fructose, D-glucose, palmi
acid, oleic acid and arachidonic acid were significantly were significantly
changed. CONCLUSION: Based on metabolomics of GC-MS detection and analysis
metabolites can be found differences between type 2 diabetes and healthy control
group, PCA diagram can effectively distinguish Type II diabetes and healthy
control group, with load diagrams and PLS-DA VIP value metabolite screening, the
resulting differences in metabolic pathways involved metabolites, including amino
acid metabolism, lipid metabolism, glucose metabolism and energy metabolism.
PMID- 27508011
TI - Collateral development and spinal motor reorganization after nerve injury and
repair.
AB - Functional recovery is often unsatisfactory after severe extended nerve defects
or proximal nerve trunks injuries repaired by traditional repair methods, as the
long regeneration distance for the regenerated axons to reinnervate their
original target end-organs. The proximal nerve stump can regenerate with many
collaterals that reinnervate the distal stump after peripheral nerve injury, it
may be possible to use nearby fewer nerve fibers to repair more nerve fibers at
the distal end to shorten the regenerating distance. In this study, the proximal
peroneal nerve was used to repair both the distal peroneal and tibial nerve. The
number and location of motor neurons in spinal cord as well as functional and
morphological recovery were assessed at 2 months, 4 months and 8 months after
nerve repair, respectively. Projections from the intact peroneal and tibial
nerves were also studied in normal animals. The changes of motor neurons were
assessed using the retrograde neurotracers FG and DiI to backlabel motor neurons
that regenerate axons into two different pathways. To evaluate the functional
recovery, the muscle forces and sciatic function index were examined. The muscles
and myelinated axons were assessed using electrophysiology and histology. The
results showed that all labeled motor neurons after nerve repair were always
confined within the normal peroneal nerve pool and nearly all the distribution of
motor neurons labeled via distal different nerves was disorganized as compared to
normal group. However, there was a significant decline in the number of double
labeled motor neurons and an obvious improvement with respect to the functional
and morphological recovery between 2 and 8 months. In addition, the
tibial/peroneal motor neuron number ratio at different times was 2.11+/-0.05,
2.13+/-0.08, 2.09+/-0.12, respectively, and was close to normal group (2.21+/
0.09). Quantitative analysis showed no significant morphological differences
between myelinated nerve fibers regenerated along the two distal nerves except
for the number of nerve fibers, which was higher in the tibial nerve. The ratio
of distal regenerated axon numbers to proximal donor nerve axon numbers was about
3.95+/-0.10, 4.06+/-0.19 and 3.87+/-0.23, respectively. This study demonstrated
that fewer nerve fibers can regenerate a large number of collaterals which
successfully repopulate both distal nerves and lead to the partial recovery of
lost functions. It may provide a new method to repair severe extended nerve
defects or proximal nerve trunks injuries.
PMID- 27508012
TI - Gax regulates human vascular smooth muscle cell phenotypic modulation and
vascular remodeling.
AB - Abnormal phenotypic modulation of vascular smooth muscle cells (VSMCs) is a
hallmark of cardiovascular diseases such as atherosclerosis, hypertension and
restenosis after angioplasty. Transcription factors have emerged as critical
regulators for VSMCs function, and recently we verified inhibiting transcription
factor Gax was important for controlling VSMCs proliferation and migration. This
study aimed to determine its role in phenotypic modulation of VSMCs. Western blot
revealed that overexpression of Gax increased expression of VSMCs differentiation
marker genes such as calponin and SM-MHC 11. Then, Gax overexpression potently
suppressed proliferation and migration of VSMCs with or without platelet-derived
growth factor-induced-BB (PDGF-BB) stimuli whereas Gax silencing inhibited these
processes. Furthermore, cDNA array analysis indicated that Rap1A gene was the
downstream target of Gax in human VSMCs. And overexpression of Gax significantly
inhibited expression of Rap1A in VSMCs with or without PDGF-BB stimuli. Moreover,
overexpression of Rap1A decreased expression of VSMCs differentiation marker
genes and increased proliferation and migration of VSMCs with or without PDGF-BB
stimuli. Finally, Gax overexpression significantly inhibited the neointimal
formation in carotid artery injury of mouse models, specifically through
maintaining VSMCs contractile phenotype by decreasing Rap1A expression. In
conclusion, these results indicated that Gax was a regulator of human VSMCs
phenotypic modulation by targeting Rap1A gene, which suggested that targeting Gax
or its downstream targets in human VSMCs may provide an attractive approach for
the prevention and treatment of cardiovascular diseases.
PMID- 27508013
TI - Follicular helper T cell exhaustion induced by PD-L1 expression in hepatocellular
carcinoma results in impaired cytokine expression and B cell help, and is
associated with advanced tumor stages.
AB - Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is one of the most
common cancers in HBV-endemic regions, with irreversible progression and poor
prognosis. HBV-related HCC patients lack effective antiviral/antitumor B cell
antibody responses. We hypothesize that dysregulation of PD-1-expressing
follicular helper T (Tfh) cell, induced by intrahepatic/intratumoral PD-L1
expression in HCC, could contribute to the defects in B cell immunity. The Tfh
responses in healthy control (HC) subjects, chronic hepatitis B (HepB) patients,
and HBV-related HCC patients were examined. Compared to HC and HepB individuals,
HCC patients showed reduced ICOS expression, IL-10 and IL-21 secretion, and
proliferation in Tfh cells. Tfh cells from stage III patients demonstrated
increased impairment than those from stage I and stage II patients. Compared to
Tfh cells from HC and HepB subjects, those from stage III HCC patients were
significantly less effective at inducing the differentiation of naive B cells
toward plasmablasts. HCC is known to upregulate hepatic PD-L1 expression, which
could suppress Tfh responses. Blocking PD-1 partially rescued the Tfh functions
in stage I and stage II HCC subjects but not in stage III HCC patients, while
treatment with recombinant PD-L1 strongly suppressed Tfh functions in all HCC
stages. Moreover, the level of IL-10 and IL-21 expression by Tfh cells was
inversely correlated with the intensity of PD-L1 expression in resected tumors.
Together, our results demonstrated an HCC-specific Tfh exhaustion, which might
have resulted from elevated PD-1 and PD-L1 signaling.
PMID- 27508014
TI - Intervention effect of pinelliae decoction for purging stomach-fire on malignant
transformation of bone marrow mesenchymal stem cells in the gastric cancer
microenvironment.
AB - OBJECTIVE: The study aimed to simulate the microenvironment of gastric cancer to
promote the malignant transformation of bone marrow mesenchymal stem cells
(BMSCs) and further evaluate the effect of Pinelliae Decoction for Purging
Stomach-Fire and its disassembled prescriptions on BMSCs. METHODS: Transwell co
culture was performed on the human gastric cancer cell strains BGC-823 and BMSCs
to simulate the microenvironment of gastric cancer. The drug-containing serum
prepared by Pinelliae Decoction for Purging Stomach-Fire and its disassembled
prescriptions was used, and its influence on BMSCs with malignant transformation
was observed. RESULTS: BMSCs were harvested successfully from the rat bone
marrow, and flow cytometer identification indicated that CD44+/CD34- cells
accounted for 70.64%. The co-culture of BGC-823 cells can induce malignant
transformation of BMSCs. And the drug-containing serum can induce G2 phase
arrest, inhibit cell proliferation, simultaneously inhibit TERT and c-myc
expression, lower the cellular ability of chemotactic migration, inhibit the
tumor-forming ability of BGC-823 in nude rats and promote the tumor apoptosis.
CONCLUSION: The effective components of Pinelliae Decoction for Purging Stomach
Fire in gastric cancer treatment are pinelliae and dried ginger, and the main
acting mechanism is to inhibit tumor cell proliferation and chemotactic migration
and promote apoptosis.
PMID- 27508015
TI - Immunotherapy with dendritic cells and cytokine-induced killer cells for MDA-MB
231 breast cancer stem cells in nude mice.
AB - OBJECTIVE: To compare the effects and safety of immunotherapy using different
methods to load DC-CIK cells for MDA-MB-231 breast cancer stem cells. METHODS: A
breast cancer model was established in BALB/c nude mice using breast cancer stem
cells. All mice were randomly divided into six groups, and each group had three
nude mice: the blank control group, the DC-CIK group (group D), the MDA-MB-231
CSC whole-cell lysate DC-CIK group (group L-D), the MDA-MB-231 CSC RNA DC-CIK
group (group R-D), the THP DC-CIK group (group T-D) and group THP. Nude mice in
groups D, L-D, R-D and T-D were injected with CSCs; 4 days later, the mice were
inoculated with 1 * 10(6) DC-CIK cells via the tail vein. This injection was
repeated 2 times a week for three weeks. The mice in groups THP and T-D were
injected with a 5 mg/Kg dose of THP chemotherapeutic agents via the tail vein the
day before DC-CIK injection, which was repeated one time a week for three weeks.
Nude mice in the blank control group were injected with normal saline. The
weights and sizes of the tumors were measured after the mice were euthanized. The
expression of c-Myc, a key proto-oncogene associated with the Akt signaling
pathway, was detected with RT-PCR. RESULTS: The tumor growth rates in each group
were as follows: group L-D < group R-D < group D < group T-D < blank control
group < group THP. The nude mice in groups L-D, R-D and D were normal, active and
had a healthy appetite. The mice in groups T-D and THP were lethargic, less
active and showed loss of appetite, and their caudal vein was easy to stimulate.
The mice in the blank control group were sacrificed during the third week or when
their tumors developed ulceration. Compared with the blank control group, c-Myc
gene expression was reduced in the tumors of the five experimental groups.
CONCLUSION: The results showed that DC-CIK cells stimulated by different methods
were highly effect against MDA-MB-231 breast cancer stem cells in nude mice in
all groups, especially in group L-D. DC-CIK immunotherapy may provide a new
strategy for the clinical treatment of breast cancer.
PMID- 27508016
TI - T helper 17 and T helper 1 cells are increased but regulatory T cells are
decreased in subchondral bone marrow microenvironment of patients with rheumatoid
arthritis.
AB - OBJECTIVES: The present study is to investigate the profiles of Th17, Th1 and
Treg cells in bone marrow of patients with rheumatoid arthritis (RA). METHODS:
Flow cytometry was used to analyze the frequencies of Th17, Th1 and Treg cells in
paired peripheral blood and bone marrow of 26 RA patients and 11 osteoarthritis
(OA) patients, as well as 10 healthy controls. In addition, the disease activity
was analyzed by the 28-joint disease activity score (DAS28). RESULTS: The
frequencies of Th17 and Th1 cells were significantly elevated in bone marrow of
RA patients. Importantly, Th17 and Th1 cells were significantly elevated in bone
marrow compared with the matched peripheral blood from RA patients. However, Treg
cells were significantly decreased in bone marrow of RA patients compared with
the matched peripheral blood of RA patients and bone marrow of osteoarthritis
patients and healthy controls. Moreover, the frequencies of tumor necrosis factor
alpha-producing T cells were significantly elevated in bone marrow from RA
patients. Additionally, Th17 and Th1 cells in bone marrow were positively
correlated with DAS28, while Treg cells were negatively correlated with DAS28.
CONCLUSIONS: The present study demonstrates that Th17 and Th1 cells are markedly
increased in bone marrow from RA patients. By contrast, Treg cells are
significantly decreased in bone marrow from RA patients. These results suggest
that local abnormality of Th17, Th1 and Treg cells in bone marrow of RA patients
may contribute to bone destruction in skeletal system.
PMID- 27508017
TI - Wallichinine reverses ABCB1-mediated cancer multidrug resistance.
AB - Overexpression of ABCB1 in cancer cells is one of the main reasons of cancer
multidrug resistance (MDR). Wallichinine is a compound isolated from piper
wallichii and works as an antagonist of platelet activiating factor receptor to
inhibit the gathering of blood platelet. In this study, we investigate the effect
of wallichinine on cancer MDR mediated by ABCB1 transporter. Wallichinine
significantly potentiates the effects of two ABCB1 substrates vincristine and
doxorubicin on inhibition of growth, arrest of cell cycle and induction of
apoptosis in ABCB1 overexpressing cancer cells. Furthermore, wallichinine do not
alter the sensitivity of non-ABCB1 substrate cisplatin. Mechanistically,
wallichinine blocks the drug-efflux activity of ABCB1 to increase the
intracellular accumulation of rhodamine 123 and doxorubicin and stimulates the
ATPase of ABCB1 without alteration of the expression of ABCB1. The predicted
binding mode shows the hydrophobic interactions of wallichinine within the large
drug binding cavity of ABCB1. At all, our study of the interaction of
wallichinine with ABCB1 presented herein provides valuable clues for the
development of novel MDR reversal reagents from natural products.
PMID- 27508018
TI - Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via
lncRNA TUG1 up-regulating the expression of miR-26a.
AB - Endothelial cell (EC) apoptosis is a crucial process for the development of
atherosclerosis. Tanshinol is reported to protect vascular endothelia and
attenuate the formation of atherosclerosis. However, the potential molecule
mechanism of the protective role of tanshinol in atherosclerosis need to be
further investigated. ApoE(-/-)mice were fed with a high-fat diet and treated
with tanshinol to detect the effect of tanshinol on endothelial cells apoptosis
with TUNEL staining assay. qRT-PCR and Western blot were performed to examine the
expression of TUG1 and miR-26a in endothelial cells. RNA-binding protein
immunoprecipitation assay was performed to verify the relationship between TUG1
and miR-26a. It has been shown that tanshinol reduced the aortic atherosclerotic
lesion area in the entire aorta and aortic sinus in a concentration dependent
manner, and suppressed the endothelial cells apoptosis in ApoE(-/-) mice. We
further found that the mRNA level of TUG1 was reduced and the expression of miR
26a was up-regulated by tanshinol in endothelial cells. In addition, TUG1 down
regulated the expression of miR-26a in ECV304 cells. Finally, it was shown that
overexpression of TUG1 removed the reversed effect of tanshinol on oxidized low
density lipoprotein (ox-LDL)-induced endothelial cells apoptosis. Taken together,
our study reveals that tanshinol could attenuate the endothelial cells apoptosis
in atherosclerotic ApoE(-/-) mice. Moreover, low TUG1 expression and high level
of miR-26a are associated with the endothelial protecting effect of tanshinol.
PMID- 27508019
TI - miR-144 reverses chemoresistance of hepatocellular carcinoma cell lines by
targeting Nrf2-dependent antioxidant pathway.
AB - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
worldwide. Chemoresistance occurrence is a major cause of treatment failure in
HCC. Currently, extensive research has revealed diverse mechanisms for
chemoresistance, but the molecular mechanisms underlying the role of miRNAs in
resistance to 5-FU are not confirmed in HCC cells. By quantitative real-time
polymerase chain reaction (qRT-PCR) analysis, we found that miR-144 was
significantly decreased in HCC cell lines. It has been further demonstrated that
miR-144 were significantly down-regulated in Bel-7402/5-FU cells compared with
parental Bel-7402 cells by qRT-PCR and western blot. The expression of Nrf2 was
reversely correlated to that of miR-144 in HCC cells. Moreover, Enhancement of 5
FU-induced cytotoxicity and apoptosis are resulted from the transfection with miR
144 mimics in Bel-7402/5-FU cells. Mechanically, miR-144 promoted nuclear factor
erythroid-2-related factor-2 (Nrf2) mRNA degradation by directly targeting the
Nrf2 3'untranslated region (3'UTR). In addition, ectopic expression of miR-144 in
Bel-7402/5-FU cells reduced the levels of Nrf2 and inhibited the transcription of
Nrf2-dependent HO-1 gene, thus contributing to 5-FU sensibilization. Conversely,
re-expression of Nrf2 partly attenuated the chemosensibilization of miR-144. Our
study showed that miR-144 serves as a potential chemoresistance-reversal agent in
hepatocellular carcinoma cells, which is at least partly due to the down
regulation of Nrf2-dependent antioxidant pathway.
PMID- 27508020
TI - Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.
AB - Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor
tyrosine kinases family. It has previously been reported to be expressed in B
cells and has an important role in B-cell malignancies. While the roles of Btk in
the pathogenesis of certain B-cell malignancies are well established, the
functions of Btk in gastric carcinoma have never been investigated. Herein, we
found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer
cells. Knockdown of Btk expression selectively inhibits the growth of gastric
cancer cells, but not that of the normal gastric mucosa epithelial cell, which
express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an
additive inhibitory effect on gastric cancer cell growth. Treatment of gastric
cancer cells, but not immortalized breast epithelial cells with ibrutinib results
in effective cell killing, accompanied by the attenuation of Btk signals.
Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo
sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma
patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor
cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma
cells. Given these promising preclinical results for ibrutinib in gastric
carcinoma, a strategy combining Btk inhibitor warrants attention in gastric
cancer.
PMID- 27508021
TI - miR-448 suppresses proliferation and invasion by regulating IGF1R in colorectal
cancer cells.
AB - Accumulating evidence has demonstrated that miR-448 expression was downregulated,
and exerted tumor suppressor roles in several types of cancer. However, the
biological function and underlying mechanism of miR-448 in colorectal cancer
(CRC) have not been elucidated. In this study, we detected the miR-448 expression
in CRC tumor tissues and adjacent normal tissues (ANT) and five colorectal cancer
cell lines by real time quantitative RT-PCR (qRT-PCR). Cell proliferation, colony
formation, migration and invasion were investigated in CRC cells transfected miR
448 mimic or negative control mimic by MTT, colony forming, wound healing and
transwell invasion assays, respectively. Target gene was identified by
bioinformatic prediction, dual-luciferase reporter assay, qRT-PCR and Western
blot. Our data proved that miR-448 expression was downregulated in CRC tissues
and cell lines, and was inversely associated with advanced tumor-node-metastasis
(TNM) stage (P < 0.01), and lymph node metastasis (P < 0.01). Overexpression of
miR-448 suppressed CRC cell proliferation, colony formation, migration, and
invasion. Moreover, we identified insulin-like growth factor 1 receptor (IGF1R)
as a direct target gene of miR-448 in CRC cell. IGF1R expression was upregulated
in CRC tissues and cell lines, and its expression was negatively correlated with
the expression level of miR-448 in CRC tissues(r = -0.569, P = 0.002). In
addition, IGF1R overexpression rescued the suppressive effect of miR-448-mediated
CRC on cell proliferation, colony formation, migration and invasion. These
results suggested that miR-448 might serve as a tumor suppressor in CRC partly
through targeting IGF1R.
PMID- 27508022
TI - MiR-497 enhances metastasis of oral squamous cell carcinoma through SMAD7
suppression.
AB - SMAD7 is a key inhibitor of transforming growth factor beta (TGFbeta) receptor
signaling, which regulates the alteration of cancer cell invasiveness through
epithelial-mesenchymal cell conversion. Since microRNAs (miRNAs) play a potential
role in the tumorigenesis, cancer cell growth and metastases of oral squamous
cell carcinoma (OSCC), determination of the involved miRNAs that may regulate
SMAD7-mediated OSCC cell invasion appears to be one important question. Here, we
found that the levels of miR-497 were significantly increased and the levels of
SMAD7 were significantly decreased in OSCC specimens, compared to the paired
adjacent non-tumor tissue. Moreover, miR-497 and SMAD7 inversely correlated in
OSCC specimens. The 5-year survival of the patients with higher miR-497 levels in
the resected OSCC was worse than those high miR-497 levels. Bioinformatics
analyses showed that miR-497 targeted the 3'-UTR of SMAD7 mRNA to inhibit its
translation, which was proved by luciferase reporter assay. Furthermore, miR-497
overexpression increased SMAD7-suppressed cell invasion, while miR-497 depletion
decreased SMAD7-suppressed cell invasion in OSCC cells, in both a transwell cell
invasion assay and a scratch would healing assay. Together, our data suggest that
suppression of miR-497 in OSCC cells may promote cancer cell invasion via
suppression of SMAD7, and highlight miR-497 as an intriguing therapeutic target
to prevent OSCC metastases.
PMID- 27508023
TI - Effects of the extract of Ginkgo biloba on the differentiation of bone marrow
mesenchymal stem cells in vitro.
AB - The balance of osteogenesis and adipogenesis in bone marrow mesenchymal stem
cells (BMSCs) is disrupted in osteoporosis. This study was designed to
investigate the effects of extract of Ginkgo biloba (EGB) on proliferation,
osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells
in vitro. The effect of EGB on proliferation was evaluated by CCK-8 assay and
flow cytometry. Osteogenic differentiation was evaluated by Alizarin Red S
staining and Alkaline phosphatase assay. Adipogenic differentiation was evaluated
by Oil Red O staining. Quantitative real-time polymerase chain reaction (Real
time PCR) was used to detect the expression of osteogenic specific genes (BMP-2,
Runx2 and Colla1) and adipogenic specific genes (ap2, PPARgamma). EGB did not
significantly affect proliferation of BMSCs. However, it increased the calcium
accumulation and significantly promoted the activity of alkaline phosphatase,
especially when the concentration of EGB reached 150 ug/mL. EGB dose-dependently
inhibited the adipogenic ability of BMSCs. The osteogenic-related genes (BMP-2,
Runx2, Colla1) were overexpressed while the expression of genes involved in
adipogenesis, such as PPAR-gamma and ap2, was decreasing with the increase of EGB
concentration. Our data proves that EGB inhibited adipocyte differentiation and
enhanced osteogenic differentiation in BMSCs, but had no effect on the
proliferation of BMSCs.
PMID- 27508024
TI - Inhibition of spinal UCHL1 attenuates pain facilitation in a cancer-induced bone
pain model by inhibiting ubiquitin and glial activation.
AB - The present study examined alterations of spinal ubiquitin C-terminal hydrolase
L1 (UCHL1), ubiquitin expression and glial activation in the cancer-induced bone
pain rats. Furthermore, whether inhibition of spinal UCHL1 could alleviate cancer
induced bone pain was observed. The CIBP model was established by intrathecal
Walker 256 mammary gland carcinoma cells in SD rats. The rats of CIBP developed
significant pain facilitation in the Von Frey test. Double immunofluorescence
analyses revealed that in the spines of CIBP rats, ubiquitin co-localized with
NeuN, Iba-1 or GFAP; UCHL1 and NeuN were co-expressed and UCHL1 also co-localized
with ubiquitin. The CIBP model induced up-regulation of ubiquitin and UCHL1 in
the spines, as well as glial activation. Inhibition of spinal UCHL1 attenuated
pain facilitation by down-regulation of ubiquitin expression and glial
activation. in the CIBP rats. Our data suggests that UCHL1/ubiquitin distributed
and increased in the spines of CIBP rats, that glial activation also increased in
the CIBP model and that inhibition of spinal UCHL1 may be an effective method to
alleviate cancer-induced bone pain.
PMID- 27508025
TI - Effects of pterostilbene on treating hyperprolactinemia and related mechanisms.
AB - Hyperprolactinemia (HPRL) frequently causes primary menopause and reproductive
disorders. Pterostilbene is known to have anti-inflammation and modulation on
cell apoptosis. However, its role in treating HPRL and potential mechanisms
remain unclear yet. Healthy female virgin SD rats were randomly assigned into
control, HPRL model group, bromocriptine treatment group, and low (20 mg/kg) and
high (40 mg/kg) pterostilbene treatment groups. All groups except control ones
received metoclopramide hydrochloride injection for generating HPRL model. Uterus
and ovarian index in all animals were monitored. Prolactin (PRL), estradiol (E2),
follicle stimulating hormone (FSH) and luteinizing hormone (LH) were quantified
by ELISA. Caspase 3 activity was assayed, with real time PCR measuring Bcl-2 and
Bax mRNA levels. HPRL rats had lower uterus and ovarian index, accompanied with
elevated PRL, caspase 3 activity, Bax expression, and decreased FSH, LH, E2 and
Bcl-2 expression as compared to control group (p<0.05). Pterostilbene treatment
significantly increased uterus and ovarian index, FSH, LH, E2 and Bcl-2
expression, and decreased PRL, caspase 3 activity and Bax expression as compared
to control group (p<0.05). 40 mg/kg pterostilbene had similar efficacy as those
of bromocriptine. Pterostilbene exerts its function in the treatment of HPRL via
modulating apoptosis-anti-apoptosis homeostasis, inhibiting serum PRL level, and
regulating secretion of gonadotropin hormones.
PMID- 27508026
TI - MiR-122 targets VEGFC in bladder cancer to inhibit tumor growth and angiogenesis.
AB - Previous studies indicate that microRNA-122 (miR-122) is down-regulated in
several cancer cells and regulates cell apoptosis, proliferation, metastasis, and
tumor angiogenesis. However, the mount of miR-122 in bladder cancer and the
pivotal molecular mechanisms of miR-122 used to regulate bladder carcinogenesis
and angiogenesis remain to be clarified. Here, we reveal that miR-122 expression
is down-regulated in human bladder cancer tissues and cell lines. MiR-122
represses vascular endothelial growth factor C (VEGFC) post-transcriptional
expression by directly binding to its 3'-UTR. The protein kinase B (AKT) and
mammalian target of rapamycin (mTOR), which are the most important downstream
molecules of VEGFC, are also decreased in bladder cancer cell after miR-122
overexpression. Furthermore, miR-122 over-expression decreases bladder cancer
cell migration, invasion, colony formation in vitro and slow bladder cancer
growth and angiogenesis in vivo. Finally, miR-122 sensitizes bladder cancer cells
to cisplatin-induced apoptosis. Taken together, these studies suggest that miR
122 serves as a tumor suppressor and down-regulating VEGFC expression, leading to
the inhibition of bladder cancer growth and angiogenesis.
PMID- 27508027
TI - Treatment of chronic ulcer in diabetic rats with self assembling nanofiber gel
encapsulated-polydeoxyribonucleotide.
AB - OBJECTIVE: This study aims to explore the treatment effects of chronic ulcer in
diabetic rats with self assembling nanofiber gel encapsulated
polydeoxyribonucleotide. METHODS: Diabetic skin ulcer mouse model was established
in this study. They were divided into control group, common wound group and
infectious wound group. Human embryonic fibroblast cells and vascular endothelial
cells were treated with short poly-N-acetyl glucosamine nanofibers and
polydeoxyribonucleotide. Their effects on cell proliferation, revascularization
and inhibiting infection were detected by RT-PCR, western-blotting, HE staining
and immunohistochemical methods respectively. RESULTS: The expression levels of
cytokines and angiogenic factors increased in the treatment groups especially in
sNAG encapsulated-PDRN group. HE staining results indicated that PDRN, sNAG and
sNAG encapsulated-PDRN could improve the wound healing, immunohistochemical
results showed that PDRN, sNAG and sNAG encapsulated-PDRN promoted cell
proliferation and new vessel formation especially sNAG encapsulated-PDRN.
CONCLUSIONS: sNAG encapsulated-PDRN may have a potential application in the
treatment of diabetic ulcers and chronic wound healing.
PMID- 27508028
TI - Erianin inhibits the proliferation of T47D cells by inhibiting cell cycles,
inducing apoptosis and suppressing migration.
AB - Erianin is a natural product extracted from Dendrobiumchrysotoxum. To investigate
the antitumor activity of Erianin in estrogen receptor (ER) positive breast
cancer, we treated T47D cells with Erianin and evaluated the effects of Erianin
treatment on multiple cancer-associated pathways. Erianin inhibited the
proliferation of T47D cells effectively. Erianin induced apoptosis in T47D cells
through reducing Bcl-2 expression and activating caspase signaling. Furthermore,
it also suppressed the expression of CDKs and caused cell cycle arrest. In
addition, Erianin treatment suppressed the migration of T47D cells, most likely
through regulating the homeostatic expression of MPP and TIMP. Meanwhile, Erianin
did not affect the proliferation of normal breast epithelial cell line MCF10A.
Together, these results demonstrated that Erianin might have the potential to be
an effective drug to treat the ER positive breast cancer.
PMID- 27508029
TI - Rescue of hypertension-related impairment of angiogenesis by therapeutic
ultrasound.
AB - We examined the hypothesis that therapeutic ultrasound (TUS) treatment would
rescue the hypertension-related inhibition of ischemia-induced angiogenesis. TUS
protects against endothelial dysfunction, but it is little known that the effect
of TUS treatment on angiogenesis inhibited by hypertension. 20-week-old male
spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly
allocated to 4 groups: SHR; TUS treated SHR (SHR-TUS); WKY and TUS treated WKY
(WKY-TUS). After undergoing excision of the left femoral artery, the ischemic
skeletal muscles were treated with extracorporeal TUS for 9 minutes of daily
exposure (frequency of 1 MHz, intensity of 0.3 W/cm(2)) for 14 consecutive days.
We found that TUS normalized the blood perfusion in SHR-TUS accompanied by
elevated capillary density. Similar results were found in the protein expression
of angiogenic factors. TUS treatment also enhanced peripheral capillary density
in WKY rats and restored the capillary rarefaction in hypertension by elevating
the protein levels of endothelial nitric oxide synthase (eNOS), hypoxic inducible
factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF) and
phosphorylated Akt (p-Akt) in vivo. Our data demonstrated that TUS treatment
ameliorated hypertension-related inhibition of ischemia-induced angiogenesis, at
least in part, via an NO-dependent manner.
PMID- 27508030
TI - Hypothalamic gastrin-releasing peptide receptor mediates an antidepressant-like
effect in a mouse model of stress.
AB - Evidence has shown that gastrin-releasing peptide receptor (GRPR) is involved in
responses to stress and anxiety. The primary role of GRPR is to stimulate
corticotrophin-releasing hormone (CRH) or adrenocorticotropic hormone (ACTH)
secretion. Thus, the mechanisms of GRPR signaling should be elucidated to
discover novel therapeutic targets for treating depression. This study aimed to
investigate GRPR alterations in the C57 mouse hypothalamus after the animals were
subjected to stress and fluoxetine treatments. Specifically, we subjected the
mice to isolation and chronic unpredictable mild stress (CUMS) for three weeks to
establish an experimental model of depression. These mice were subsequently
treated with fluoxetine for three weeks. Then, we performed the sucrose
preference test and the open field test and measured food intake and body weight
to explore the effects of stress and fluoxetine on activity and anhedonia. After
fluoxetine treatment, we also assessed changes in the levels of GRPR expression
in the hypothalamus using immunohistochemistry, western blotting, and real-time
quantitative PCR (RT-PCR). We found that stressed mice showed significant
reductions in locomotion, food intake/body weight, and sucrose preference; these
reduced parameters indicated a state of anhedonia. Marked increases in mRNA and
protein expression of GRPR in the hypothalamus of CUMS-exposed mice were also
observed, although treatment with fluoxetine reversed these stress-induced
changes. Our results also demonstrated the feasibility and effectiveness of the
C57 mouse model of depression established by CUMS and isolation. After fluoxetine
treatment was administered, the animals' depression symptoms were alleviated, and
these behavioral alterations were accompanied by specific changes in mRNA and
protein expression of GRPR in the hypothalamus. These results suggest that GRPR
may be implicated in depression; therefore, new therapeutic targets of depression
focused on GRPR signaling should be explored.
PMID- 27508031
TI - miR-145 suppresses breast cancer cell migration by targeting FSCN-1 and
inhibiting epithelial-mesenchymal transition.
AB - MicroRNAs (miRNAs), small non-coding RNAs, regulate fundamental cellular and
developmental processes such as cell growth, apoptosis, migration, and invasion.
In our present study, we investigated the inhibitory role of miR-145 on breast
cancer cell migration as well as its underlying mechanism. Wound healing assay
and transwell migration assay showed that ectopic expression of miR-145
significantly inhibited breast cancer cell migration. Bioinformatics analysis
revealed that FSCN-1 was a putative target of miR-145. The expression of FSCN-1
varied among four different breast cancer cells, and inversely correlated with
miR-145 levels. Moreover, miR-145 mimic transfection enhanced the expression of
FSCN-1 in Bcap-37 and HCC-1937 cells. We also found that siRNA- mediated down
regulation of FSCN-1 inhibited cell motility in breast cancer cells. In addition,
we found that up-regulation of miR-145 blocked EMT and decreased the expression
of MMP-2/9 in breast cancer cells. These results reveal a new link between miR
145, FSCN-1 and EMT in the regulation of breast cancer migration.
PMID- 27508032
TI - MicroRNA-765 regulates neural stem cell proliferation and differentiation by
modulating Hes1 expression.
AB - Neural stem cells (NSCs) are multipotent, self-renewing and undifferentiated
cells that have the ability to differentiate to both glial and neuronal lineages.
miRNAs act a key role in regulating neuronal fate and self-renewal of NSCs. In
this study, we found that ectopic expression of miR-765 promoted NSCs
proliferation. Moreover, miR-765 overexpression increased the ki-67 and beta
tubulin-III expression inNSCs. Overexpression of miR-765 inhibited the expression
of GFAP in NSCs. Furthermore, Hes1 was identified as a direct target gene of miR
765 in NSCs. Overexpression of Hes1 decreased miR-765-induced proliferation of
NSCs and inhibited NSCs differentiation to neurons in miR-765-treated NSCs. These
results demonstrated that miR-765 acted a crucial role in NSCs differentiation
and proliferation by inhibiting Hes1 expression.
PMID- 27508033
TI - Tanshinone IIA inhibits apoptosis in the myocardium by inducing microRNA-152-3p
expression and thereby downregulating PTEN.
AB - Progressive loss of cardiac myocytes through apoptosis contributes to heart
failure (HF). In this study, we tested whether tanshinone IIA, one of the most
abundant constituents of the root of Salvia miltiorrhiza, protects rat myocardium
derived H9C2 cells against apoptosis. Treatment of H9C2 cells with tanshinone IIA
inhibited angiotensin II-induced apoptosis by downregulating the expression of
PTEN (phosphatase and tensin homolog), a tumor suppressor that plays a critical
role in apoptosis. Furthermore, tanshinone IIA was found to inhibit PTEN
expression by upregulating the microRNA miR-152-3p, a potential PTEN regulator
that is highly conserved in both rat and human. Notably, the antiapoptotic effect
of tanshinone IIA was partially reversed when H9C2 cells were transfected with an
inhibitor of miR-152-3p. Collectively, our findings reveal a previously
unrecognized mechanism underlying the cardioprotective role of tanshinone IIA,
and further suggest that tanshinone IIA could represent a promising drug
candidate for HF therapy.
PMID- 27508034
TI - Effects of osteoprotegerin, RANK and RANKL on bone destruction and collapse in
avascular necrosis femoral head.
AB - Avascular necrosis of femoral head (AVFH) is a clinically recalcitrant disease of
hip that leads to joint destruction. Osteoprotegerin (OPG), receptor activator of
nuclear factor kappa-B (RANK) and RANK ligand (RANKL) regulates the balance,
maturation and function of osteoclast and bone remodeling. This study aims to
investigate molecular pathways which leads to AVN by studying expression profile
of OPG, RANK and RANKL genes. Quantitative Real Time-PCR is used to evaluate mRNA
expression of OPG, RANK and RANKL. mRNA and protein level in normal and necrotic
tissue from 42 samples of ANFH specimens were analyzed. OPG and RANKL protein
levels are estimated by western blotting. The results indicated that OPG mRNA
levels are higher but not significantly different in necrotic tissue than that in
normal tissue (P>0.05). Although expression of RANK and RANKL is significantly
lower than that of OPG, RANK and RANKL mRNA levels are higher in necrotic tissue
than normal tissue (P<0.05). Protein levels of OPG and RANKL show no significant
difference. In conclusion, OPG, RANK and RANKL play important role in progress of
bone remodeling in necrotic area and in disturbance of bone homeostasis, which
might have an effect on bone destruction and subsequent collapse of hip joint.
PMID- 27508035
TI - Relationship between PI3K pathway and angiogenesis in CIA rat synovium.
AB - To investigate the expression of hypoxia inducible factor (HIF-1alpha) and
vascular endothelial growth factor (VEGF) in the synovium of collagen-induced
arthritis (CIA) joint, and whether the PI3K pathway regulates angiogenesis in
rheumatoid arthritis or not. A randomized controlled according to the principle
of the rats were divided into normal control group (10 rats) and the experimental
group (40 rats). The experimental group rats were established as type II collagen
plus adjuvant Freund's complete adjuvant-induced arthritis model. HIF-1alpha and
VEGF proteins' expression in serum of CIA rats group and normal control group
were detected by ELISA. Microvessel density (MVD) in synovial tissue of CIA rats
group and normal control group were detected by immunohistochemistry (IHC)
staining. The protein expression of PTEN, PI3K, and AKT in synovial tissue were
detected by Western Blot. Compared with normal control group, toes and ankle
swelling and arthritis index (AI) of CIA rat increased, and the expression of
VEGF and HIF-1alpha proteins in peripheral serum increased, IHC showed that MVD
was significantly higher than that of the control group, and the difference was
statistically significant (p<0.05). Western Blot results showed that PI3K and AKT
proteins expression in CIA synovial tissue of rats increased, while the
expression of PTEN protein decreased. Correlation analysis showed that VEGF and
HIF-1 levels in the peripheral serum of CIA rats were positively correlated with
arthritis index (AI); the contents of HIF-1alpha and VEGF in the peripheral serum
of CIA rats were positively correlated with MVD in synovium tissue. The CIA rat
model regulated the expression of HIF-1alpha and VEGF proteins in peripheral
serum by PI3K signaling pathway, and then regulated neovascularization in RA.
PMID- 27508036
TI - Effects of immobilizations stress with or without water immersion on the
expression of atrial natriuretic peptide in the hearts of two rat strains.
AB - Atrial natriuretic peptide (ANP) is produced and released by mammalian
cardiomyocytes and induces natriuresis, diuresis, and lowering of blood pressure.
The present study examined localization of ANP and a possible role of the
hypothalamic-pituitary-adrenal axis (HPA) activity on the expression of proANP
gene in the heart. The Sprague Dawley (SD) and Lewis (LE) rat strains were used.
The animals were exposed to the two types of stress: immobilization and
immobilization combined with water immersion for 1 hour. Localization of ANP was
detected by immunohistochemistry and expression of the proANP mRNA by real-time
qPCR in all heart compartments of control and stressed animals after 1 and 3
hours after stress termination (IS1, IS3, ICS1, and ICS3). Relatively high
density of ANP-immunoreactivity was observed in both atria of both rat strains.
In control rats of both strains, the expression of the proANP mRNA was higher in
the atria than in ventricles. In SD rats with the intact HPA axis, an
upregulation of ANP gene expression was observed in the right atrium after IS1,
in both atria and the left ventricle after IS3 and in the left atrium and the
left ventricle after ICS3. In LE rats with a blunted reactivity of the HPA axis,
no increase or even a downregulation of the gene expression was observed. Thus,
acute stress-induced increase in the expression of the proANP gene is related to
the activity of the HPA axis. It may have relevance to ANP-induced protection of
the heart.
PMID- 27508037
TI - Calretinin, S100 and protein gene product 9.5 immunostaining of rectal suction
biopsies in the diagnosis of Hirschsprung' disease.
AB - Evaluation of rectal suction biopsies for the ganglion cells and neural
hypertrophy is the basic modality for the diagnosis of Hirschsprung's disease
(HD). However, the traditional hematoxylin and eosin staining coupled with
acetylcholinesterase histochemistry remain challenging, especially in newborns.
Thus we conducted a prospective study to evaluate the usefulness of calretinin
combined with S100 and protein gene product 9.5 (PGP9.5) immunostaining of rectal
suction biopsies for the diagnosis of HD. A total of 195 patients were enrolled
in our study. Of the 195 patients 69% had ganglion cells on the initial
diagnostic protocol. Sixty cases were devoid of ganglion cells, and of these, 90%
and 91% showed submucosal neural hypertrophy on S-100 staining and PGP9.5
staining, respectively. Eighty-one patients underwent a colonic resection, and of
these, 59 had confirmed aganglionic segment, the other 22 patients were diagnosed
as intestinal neuronal dysplasia type B (n=13) and isolated hypoganglionosis
(n=9). Of the rest 114 patients, 51 cases underwent a full-thickness biopsy, and
HD was excluded; sixty-three patients were thoroughly followed-up with no
evidence of HD. We encountered two false-negatives and they were proved to be
short segment HD after the surgery. The sensitivity and specificity rates of our
diagnostic protocol was 96.49% (95% CI, 0.88-0.99) and 100% (95% CI, 0.97-1.00),
respectively, excluding 5 patients with inconclusive results. Our findings
demonstrated that calretinin coupled with S100 and PGP9.5 immunostaining on
suction rectal biopsies is sensitive and specific for diagnosing HD.
PMID- 27508038
TI - Chidamide, a novel histone deacetylase inhibitor, inhibits the viability of MDS
and AML cells by suppressing JAK2/STAT3 signaling.
AB - Many studies have indicated that histone deacetylase (HDAC) activity is always
increased in a lot of human tumors, and inhibition of HDAC activity is a
promising new strategy in the treatment of cancers. Chidamide, a novel HDAC
inhibitor of the benzamide class, is currently under clinical trials. In this
study, we aimed to investigate the antitumor activity of Chidamide on
myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) cell lines and
explore the possible mechanism. Chidamide exhibited efficient anti-proliferative
activity on MDS and AML cells in a time- and dose-dependent manner, accompanied
by cell cycle arrest at G0/G1 phase and cell apoptosis. Importantly, Chidamide
possessed potent HDAC inhibition property, as evaluated by HDAC activity analysis
and acetylation of histone H3 and H4. Moreover, Chidamide significantly increased
the expression of Suppressors of cytokine signaling 3 (SOCS3), reduced the
expression of Janus activated kinases 2 (JAK2) and Signal transducer and
activator of transcription 3 (STAT3), and inhibited STAT3 downstream genes,
including c-Myc, Bcl-xL, and Mcl-1, which are involved in cell cycle progression
and anti-apoptosis. Therefore, we demonstrate that Chidamide exhibits potent
inhibitory effect on cell viability of MDS and AML cells, and the possible
mechanism may lie in the downregulation of JAK2/STAT3 signaling through SOCS3
upregulation. Our data provide rationale for clinical investigations of Chidamide
in MDS and AML.
PMID- 27508039
TI - Effects of microRNA-21 and microRNA-24 inhibitors on neuronal apoptosis in
ischemic stroke.
AB - OBJECTIVES: The purpose of our study was aimed to investigate the effects of
microRNA-21 (miR-21) and microRNA-24 (miR-24) inhibitors on ischemic stroke.
METHODS: MiR-21 inhibitor or miR-24 inhibitor was delivered to Sprague Dawley
(SD) rats by continuous intracerebroventricular infusion. Two days later, middle
cerebral artery occlusion (MCAO) was performed to induce ischemic stroke.
Quantitative real-time PCR was performed to confirm transfection efficiency. The
number of apoptotic neurons was detected using TUNEL method. Besides, primary
hippocampal or cortical neuronal cultures were prepared from embryonic day 16-18
C57BL/6 mice. These cells were transfected with miR-21 inhibitor, miR-24
inhibitor, or negative scramble RNA. Then the cell viability was detected after
transfection, as well as the protein levels of Caspase-3, B-cell lymphoma (Bcl)
xL, and heat shock protein (HSP) 70. RESULTS: Both the levels of miR-21 and miR
24 were significantly reduced by transfection with inhibitors compared to control
group or scramble RNA group (both P < 0.05). The apoptosis was significantly
reduced in both hippocampal neuron and cortical neuron by miR-24 inhibitor rather
than miR-21 inhibitor (P < 0.05), while the cell viability was significantly
increased compared to the control group or the scramble group (P < 0.05). In
addition, the levels of Bcl-xL and HSP70 were significantly increased, and the
levels of Caspase-3 were statistically decreased by transfection with miR-24
inhibitor. CONCLUSION: MiRNA-24 but not miR-21 inhibitor prevents apoptosis in
ischemic stroke by regulation of Bcl-xL, Caspase-3 and HSP70.
PMID- 27508040
TI - Interleukin-21 is associated with the severity of psoriasis vulgaris through
promoting CD4+ T cells to differentiate into Th17 cells.
AB - Interleukin-21 (IL-21) and T helper 17 (Th17) cells are known to be involved in
the pathogenesis of psoriasis, but little is known about their relationship in
psoriasis. Herein, we investigated whether IL-21 could regulate Th17 cell
induction in patients with psoriasis vulgaris. 32 patients with psoriasis
vulgaris and 13 healthy controls were recruited. Flow cytometry was used to
detect the frequencies of cells mainly secreting IL-21 (including IL-21+CD4+ T
and IL-21+ Th17 cells) and Th17 cells. An enzyme-linked immunosorbent assay
(ELISA) was used to determine the serum content of IL-21. Severity of the
psoriasis was evaluated by a Psoriasis Area and Severity Index (PASI) score. In
addition, the differentiation of CD4+ T cells with IL-21 and the different
frequencies of IL-21+CD4+ T cells, IL-21+ Th17 cells and Th17 cells were
assessed, as were serum levels of IL-21 in patients with moderate to severe
psoriasis before and after treatment. Our results showed that the levels of IL
21, IL-21+CD4+ T cells, IL-21+ Th17 cells and Th17 cells were significantly
increased in patients and positively associated with PASI score (P < 0.01).
Moreover, the levels of IL-21, IL-21+CD4+ T cells and IL-21+ Th17 cells were
positively correlated with the frequency of Th17 cells (P < 0.01). In vitro
experiments demonstrated that IL-21 could promote CD4+ T cells to differentiate
into Th17 cells. After a 4-week treatment of acitretin and a topical therapy, all
the immune markers observed in patients decreased significantly (P < 0.01), but
the levels remained higher than those in healthy controls (P < 0.01). These
findings indicate that IL-21 might promote Th17 cell induction in psoriasis and
might be a potential immune marker for targeting this disease.
PMID- 27508041
TI - MiR-338* suppresses fibrotic pathogenesis in pulmonary fibrosis through targeting
LPA1.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease involving
pulmonary injury associated with tissue repair, dysfunction and fibrosis.
MicroRNAs (miRNAs), as gene regulators, are assumed to regulate about one third
of genes and thus play important roles in cellular functions including
proliferation, growth, differentiation and apoptosis. Recent studies have
indicated that some miRNAs may play critical roles in the pathogenesis of
pulmonary fibrosis. In this study, we found that miR-338*(miR-338-5p), which has
been found to be associated with tumor progression, was down-regulated in
fibroblasts and TGF-beta-induced lung fibrotic tissues. Over-expression of miR
338* can partly prevent the fibrotic process induced by TGF-beta. Moreover, LPA1
was proven to be a downstream target of miR-338*. Lentivirus-mediated over
expression of miR-338* can alleviate lung fibrosis induced by bleomycin in mice.
Taken together, our results suggest that miR-338* attenuates the pathogenesis of
pulmonary fibrosis through targeting LPA1. Thus, miR-338* can be a potential
therapeutic target for the treatment of IPF.
PMID- 27508042
TI - MiR-338* targeting smoothened to inhibit pulmonary fibrosis by epithelial
mesenchymal transition.
AB - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease involving pulmonary
injury associated with tissue repair, dysfunction and fibrosis. Recent studies
indicate that some microRNAs (miRNAs) may play critical roles in the pathogenesis
of pulmonary fibrosis. In this study, we aim to investigate whether miR-338* (miR
338-5p), which has been found to be associated with tumor progression, is
associated with pathological process of pulmonary fibrosis. Balb/c mice were
treated with bleomycin (BLM) to establish IPF models. Targtscan was used to
predict the downstream target of miR-338*. Morphological changes were observed
with light microscope and epithelial to mesenchymal transition (EMT) markers were
detected by western blot. The expression of miR-338* or downstream target SMO was
analyzed by real-time quantitative RT-PCR, northern blot or western blot. MiR
338* was down-regulated in the lung tissue from mice with bleomycin-induced
pulmonary fibrosis. The smoothened (SMO) is a direct target of miR-338*, and
knocking-down the expression of SMO could partially rescue the fibrotic phenotype
of TGF-beta-induced NuLi-1 cells. Over-expression of SMO led to the fibrotic
phenotype of NuLi-1 cells even without TGF-beta treatment. These findings showed
that the over-expression of SMO contributed to the fibrotic phenotype of NuLi-1
cells by affecting the epithelial-to-mesenchymal transition (EMT) procedure.
Furthermore, in vivo, lentivirus-mediated over-expression of miR-338* can
alleviate lung fibrosis induced by bleomycin in mice. In conclusion, our results
suggest that miR-338* can target SMO to reduce the EMT procedure and thus
postpone the development of pulmonary fibrosis.
PMID- 27508043
TI - Human papillomavirus infection correlates with inflammatory Stat3 signaling
activity and IL-17 expression in patients with breast cancer.
AB - OBJECTIVES: Microbiota has been suggested in promoting chronic inflammation in
human tissues which, in turn, promotes tumor development. This study tests a
hypothesis that high-risk human papillomavirus (HR-HPV) infection may correlate
with proinflammatory Stat3 signaling activities and IL-17 levels in breast cancer
(BC) patients. MATERIALS AND METHODS: This study examined HPV infection by
GenChip technology, constitutively active Stat3 (p-Stat3) and IL-17 levels by
immunohistochemistry (IHC) using specific antibodies in 379 BC patients, together
with 245 paired adjacent breast adenosis (ABA) tissues and 100 unrelated breast
adenosis (BA) tissues. RESULTS: We obtained four major findings: (1) HR-HPV16/18
infections existed in 10.5% (34/325) of BC issues, higher than control BA tissues
(4%, 4/100, P = 0.047). (2) Using IHC methodology, BC tissues showed more
overactive p-Stat3 (2+/3+, 38.5%, 146/379) than ABA tissues (27.3%, 67/245, P <
0.001); similarly, BC also had more tissues overexpressing IL-17 (2+/3+, 61.5%,
233/379) than ABA tissues (51.8%, 127/245, P < 0.001). (3) High levels (2+/3+) of
both active p-Stat3 and IL-17 correlated with poor differentiation and lymph
nodal metastasis in BC (both with P < 0.05), but not with patients' prognosis.
(4) HR-HPV infections correlated with both active p-Stat3 (P = 0.018) and its
downstream IL-17 levels (P = 0.021) in BC tissues. CONCLUSION: There may be a
possible tri-lateral relationship among HPV infection, constitutive Stat3
activity and IL-17 level, whose collaborations could orchestrate a
proinflammatory microenvironment in breast tissues by which promote
carcinogenesis and/or facilitate progression of breast cancer.
PMID- 27508044
TI - Role of nanobacteria in the pathogenesis of kidney stone formation.
AB - OBJECTIVE: This study aimed to investigate the nanobacteria (NB) induced damage
to human tubular epithelial HK-2 cells and the potential role of NB in the kidney
stone formation. METHODS: Serum sample from 15 patients with kidney stone was
collected. Four groups were included: control, NB group, nanograde hydroxyapatite
(nHAP) and calcium oxalate monohydrate (COM) group. Catalase (CAT), malonaldehyde
(MDA) and Na(+)/K(+) ATPase activity was detected in the supernatant at 12 and 24
h. At 12 and 24 h, COM was added. RESULTS: At 12 h and 24 h, the CAT in NB group
was significantly higher than in control group and nHAP group (P<0.01). CAT at 24
h was significantly higher than in COM group (P<0.01). At 12 h and 24 h, the MDA
in NB group was significantly higher than in control group and nHAP group
(P<0.01) and significantly lower than in COM group (P<0.01). At 12 h, the
Na(+)/K(+) ATPase activity in NB group and nHAP group was significantly lower
than in control group, but dramatically increased as compared to COM group
(P<0.01). At 24 h, the Na(+)/K(+) ATPase activity in NB group and nHAP group was
significantly lower than in control group (P<0.01). CONCLUSION: NB may induce
lipid peroxidation in HK-2 cells and cause adhesion of HK-2 cells to COM in a
time-dependent manner, resulting in damage to HK-2 cells. This injury-causing
capability of NB is more potent than nHAP and might be involved in the
pathogenesis of kidney stone formation.
PMID- 27508045
TI - Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and
choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression.
AB - Mother-to-infant transmission of hepatitis B virus (HBV) plays an important role
in the chronic carrier state in China. In our studies, the response of
trophoblast cell and choriocarcinoma cell to HBV infection regarding the
expression of CD133-2 (AC141) was evaluated. Western blot and RT-PCR showed that
a high level of CD133-2 protein and mRNA in HTR-8/SVneo cells, but a low level in
JEG-3 cells. Lower proliferation and mobility, and higher apoptosis were observed
in HTR-8/SVneo cells and JEG-3-CD133-2(+) cells after HBV infection than those in
HTR-8-CD133-2(-) cells and JEG-3 cells. Our main finding is that CD133-negative
cells (HTR-8-CD133-2(-) and JEG-3) are prone to HBV infection. In the last, our
data indicated that the activation of Smad signaling pathway and the induction of
epithelial-mesenchymal transition (EMT) in CD133-negative cells after HBV
infection. In summary, our study demonstrated that CD133 is a key factor that
mediated HBV infection to trophoblast cell and choriocarcinoma cell.
PMID- 27508046
TI - Therapeutic effects of human umbilical cord mesenchymal stem cells
transplantation on hypoxic ischemic encephalopathy.
AB - OBJECTIVE: Human umbilical cord mesenchymal stem cells (hUC-MSCs) hold
substantial promise for the treatment of ischemic neurological disease, but few
clinical data are currently available about its therapeutic effects in hypoxic
ischemic encephalopathy (HIE). This study is to evaluate the effects of hUC-MSCs
transplantation on patients with HIE. Methods A total 22 patients with HIEwere
randomly divided into hUC-MSCs transplantation group (n = 12) and control group
(n = 10). After isolation, hUC-MSCs were cultured for 3 to 5 passages in vitro
and then intravenously administered to HIE patients in the transplantation group,
while the control group received routine treatment only. The outcomes of HIE
patients were evaluated at designated time points by clinical assessment scales,
including NIHSS, Barthel Index, MMSE, HAMA24, HAMD14 and UPDRS. RESULTS: hUC-MSCs
were identified by morphological analysis and flow cytometry assays before clinic
transplantation. No significant differences of demographic characteristics were
observed between the two groups of subjects. Compared to the control group, hUC
MSCs transplantation markedly improved the outcomes of HIE patients leading to
better recovery of neurological function, cognition ability, emotional reaction
and extrapyramidal function. No significant adverse effects were found in
subjects with hUC-MSCs transplantation during a 180-day follow-up period.
CONCLUSION: These data suggest that hUC-MSCs therapy markedly improves the
outcomes of patients with HIE, which is potential for the routine treatment of
ischemic neurological disease.
PMID- 27508047
TI - Sauchinone augments cardiomyocyte viability by enhancing autophagy proteins
PI3K, ERK(1/2), AMPK and Beclin-1 during early ischemia-reperfusion injury in
vitro.
AB - Background. Sauchinone has proved its anti-oxidant and anti-inflammatory
properties in various animal tissues. This study sought to illustrate its
regulatory nature on autophagy associated proteins (PI3K, ERK1/2, AMPK, and
Beclin-1) during early cardiomyocyte ischemia and subsequent reperfusion.
Methods. Cultured cardiomyocytes were subjected to simulated Ischemia/reperfusion
with and without Sauchinone pretreatment and also in the presence of autophagy
inhibitor (3-MA). Colorimetric analysis of CCK-8, LDH antibody assay as well as
Western blot analysis were performed to observe the expressions of LC3B (II) and
Beclin-1 protein (markers of autophagy), autophagy proteins (PI3K, ERK1/2 and
AMPK) and apoptotic proteins (Bax and Bcl-2) and the results were quantified into
their grey values and subjected to statistical analysis. Results. Sauchinone
demonstrated cell survival enhancing properties with increase in CCK-8 (SD =
0.553+/-0.012) and decrease in LDH (SD = 0.183+/-0.054) expressions, both of
which were best observed at test dose of 20 umol/L. At this dose, there was
increment in cellular autophagy as demonstrated by peaking of autophagy markers
LC3B-II (p<0.05) and Beclin-1 (p<0.05) with strong correlations (r = 0.99).
Similarly, the autophagy proteins, compared to control and I/R model, also showed
a significant increased level with PI3K (p<0.0001), total p-ERK1/2 (p<0.0001) and
p-AMPKalpha (p<0.0001). Simultaneously, a decrease in expressions of pro
apoptotic molecules Bax (r = 0.989, p<0.0001) with increment of in the anti
apoptotic protein Bcl-2 (r = 0.996, p<0.0001) was observed. The observed effects
on cell density, viability and autophagy was abrogated in presence of 3-MA.
Conclusions. Sauchinone enhances cell survival by promoting autophagy and
inhibiting apoptosis in cardiomyocytes during early stages of
Ischemia/reperfusion injury.
PMID- 27508048
TI - MiR-338-3p targets pyruvate kinase M2 and affects cell proliferation and
metabolism of ovarian cancer.
AB - MiR-338-3p is down-regulated in cancer, which inhibits cancer cell proliferation,
metastasis, and increases chemosensitivity, but its functions in ovarian cancer
remains unknown. The present study aims to identify the miR-338-3p targeted genes
and to investigate the associated regulatory mechanisms in ovarian cancer cell
proliferation and metabolism. Our results demonstrated miR-338-3p expression was
down-regulated in most of ovarian cancer tissues and cell lines. Restoration of
miR-338-3p expression in ovarian cancer cells could inhibit cell proliferation,
lactate production and lactate production of ovarian cancer cells. PKM2 was
verified as a target gene of miR-338-3p by luciferase assay. Further study
indicated miR-338-3p controlled ovarian cancer cell metabolism by inhibiting PKM2
expression. It is summarized that the regulatory role of miR-338-3p on PKM2
expression in ovarian cancer may play important roles in cell metabolism.
PMID- 27508049
TI - Expression of programmed death-1 ligand (PD-L1) in tumor-infiltrating lymphocytes
is associated with favorable spinal chordoma prognosis.
AB - Aberrant expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1)
proteins alters human immunoresponse and promotes tumor development and
progression. We assessed the expression status of PD-1 and PD-L1 in spinal
chordoma tissue specimens and their association with clinicopathological
characteristics of patients. Formalin-fixed paraffin-embedded tumor samples from
54 patients with spinal chordoma were collected for immunohistochemical analysis
of PD-1 and PD-L1 expression. The association of the expression levels of PD-1
and PD-L1 with clinicopathological variables and survival data were statistically
analyzed. Lymphocyte infiltrates were present in all 54 patient samples. Of 54
samples, 37 (68.5%) had both positive PD-1 and PD-L1 expression in tumor cell
membrane. Moreover, 38 (70.4%) and 12 (22.2%) had positive PD-1 and PD-L1
expression in tumor-infiltrating lymphocytes (TILs), respectively. Tumors with
positive PD-L1 expression were significantly associated with advanced stages of
chordoma (p = 0.041) and TIL infiltration (p = 0.005), and had a borderline
association with tumor grade (p = 0.051). However, positive tumor PD-L1
expression was not significantly associated with local recurrence-free survival
(LRFS) or overall survival (OS). PD-1 expression in TILs was associated with poor
LRFS (chi(2) = 10.051, p = 0.002, log-rank test). Multivariate analysis showed
that PD-L1 expression only in TILs was an independent predictor for LRFS (HR =
0.298, 95% CI: 0.098-0.907, p = 0.033), and OS (HR = 0.188, 95% CI: 0.051-0.687,
p = 0.011) in spinal chordoma patients. In conclusion, PD-L1 expression in TILs
was an independent predictor for both LRFS and OS in spinal chordoma patients.
Our findings suggest that the PD-1/PD-L1 pathway may be a novel therapeutic
target for the immunotherapy of chordoma.
PMID- 27508050
TI - Differential expression of miR-21 and miR-75 in esophageal carcinoma patients and
its clinical implication.
AB - In Xinjiang, China, esophageal carcinoma has a high incidence in Kazak and Uighur
populations. MicroRNA (miR)-21 and miR-375 are related to esophageal carcinoma.
This study thus investigated their potencials in early diagnosis and prognosis in
Kazak and Uighur populations, to provide evidences for serum markers of
esophageal cancer. A total of 126 Kazak or Uighur esophageal cancer patients were
enrolled as the disease group, along with 86 local Han patients as disease
control cohort, and 80 healthy Kazak or Uighur individuals. MiRNA expression was
detected by in situ hybridization in tissues and by qRT-PCR in serum. ROC
approach was used to evaluate the diagnostic value of miRNA on esophageal
carcinoma. Cox analysis was performed to screen factors governing prognosis. MiR
21 level was significantly elevated in both tissue and serum samples of
esophageal cancer patients, while miR-375 was down-regulated. Such difference was
more potent in disease group compared to disease control group. MiR expression
was correlated with infiltration depth, TNM stage, vascular invasion, and lymph
node metastasis. Elevated expression of miR-21 reduced the sensitivity of radio
therapy, and increased recurrence frequency. The diagnostic value of single assay
for miR-21 or miR-375 was lower than the combined assay (AUC=0.812 or 0.739 vs.
0.858). They also affected patient prognosis (OR=1.53 or 0.652). MiR-21 and miR
375 presented abnormal expression in Kazak or Uighur esophageal carcinoma
patients and were independent factors affecting prognosis. The combined assay of
miR-21 and miR-375 may help to make early diagnosis of esophageal cancer.
PMID- 27508051
TI - Ursolic acid attenuates temozolomide resistance in glioblastoma cells by
downregulating O(6)-methylguanine-DNA methyltransferase (MGMT) expression.
AB - The DNA-alkylating agent temozolomide (TMZ) is an effective chemotherapeutic
agent against malignant glioma, including glioblastoma multiforme (GBM). However,
the clinical efficacy of TMZ is limited in many patients because of O(6)
methylguanine-DNA methyltransferase (MGMT)-driven resistance. Thus, new
strategies to overcome TMZ resistance are urgently needed. Ursolic acid (UA) is a
naturally derived pentacyclic triterpene acid that exerts broad anticancer
effects, and shows capability to cross the blood-brain barrier. In this study, we
evaluated the possible synergistic effect of TMZ and UA in resistant GBM cell
lines. The results showed that UA prevented the proliferation of resistant GBM
cells in a concentration-dependent manner. Compared with TMZ or UA treatment
alone, the combination treatment of TMZ and UA synergistically enhanced
cytotoxicity and senescence in TMZ-resistant GBM cells. This effect was
correlated with the downregulation of MGMT. Moreover, experimental results with
an in vivo mouse xenograft model showed that the combination treatment of UA and
TMZ reduced tumor volumes by depleting MGMT. Therefore, UA as both a monotherapy
and a resensitizer, might be a candidate agent for patients with refractory
malignant gliomas.
PMID- 27508052
TI - Mitochondrial DNA Damage and Diseases.
AB - Various endogenous and environmental factors can cause mitochondrial DNA (mtDNA)
damage. One of the reasons for enhanced mtDNA damage could be its proximity to
the source of oxidants, and lack of histone-like protective proteins. Moreover,
mitochondria contain inadequate DNA repair pathways, and, diminished DNA repair
capacity may be one of the factors responsible for high mutation frequency of the
mtDNA. mtDNA damage might cause impaired mitochondrial function, and, unrepaired
mtDNA damage has been frequently linked with several diseases. Exploration of
mitochondrial perspective of diseases might lead to a better understanding of
several diseases, and will certainly open new avenues for detection, cure, and
prevention of ailments.
PMID- 27508053
TI - Biomarkers and recent advances in the management and therapy of sickle cell
disease.
AB - Although production of hemoglobin S, the genetic defect that causes sickle cell
disease (SCD), directly affects only red blood cells, the manifestations of SCD
are pervasive, and almost every cell type and organ system in the body can be
involved. Today, the vast majority of patients with SCD who receive modern health
care reach adulthood thanks to vaccine prophylaxis and improvements in supportive
care, including transfusion. However, once patients reach adulthood, they
commonly experience recurrent painful vaso-occlusive crises and frequently have
widespread end-organ damage and severely shortened life expectancies. Over the
last several decades, research has elucidated many of the mechanisms whereby
abnormal red blood cells produce such ubiquitous organ damage. With these
discoveries have come new ways to measure disease activity. In addition, new
pharmaceutical interventions are now being developed to address what has been
learned about disease mechanisms.
PMID- 27508054
TI - Epigenetic and microRNA regulation during osteoarthritis development.
AB - Osteoarthritis (OA) is a common degenerative joint disease, the pathological
mechanism of which is currently unknown. Genetic alteration is one of the key
contributing factors for OA pathology. Recent evidence suggests that epigenetic
and microRNA regulation of critical genes may contribute to OA development. In
this article, we review the epigenetic and microRNA regulations of genes related
to OA development. Potential therapeutic strategies may be developed on the basis
of novel findings.
PMID- 27508055
TI - Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel disease?
AB - The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis
and Crohn's disease has increased at an alarming rate. Although the specific
pathophysiology underlying IBD continues to be elusive, it is hypothesized that
IBD results from an aberrant and persistent immune response directed against
microbes or their products in the gut, facilitated by the genetic susceptibility
of the host and intrinsic alterations in mucosal barrier function. In this
review, we will describe advances in the understanding of how the interaction of
host genetics and the intestinal microbiome contribute to the pathogenesis of
IBD, with a focus on bacterial metabolites such as short chain fatty acids
(SCFAs) as possible key signaling molecules. In particular, we will describe
alterations of the intestinal microbiota in IBD, focusing on how genetic loci
affect the gut microbial phylogenetic distribution and the production of their
major microbial metabolic product, SCFAs. We then describe how enteroendocrine
cells and myenteric nerves express SCFA receptors that integrate networks such as
the cholinergic and serotonergic neural systems and the glucagon-like peptide
hormonal pathway, to modulate gut inflammation, permeability, and growth as part
of an integrated model of IBD pathogenesis. Through this integrative approach,
we hope that novel hypotheses will emerge that will be tested in reductionist,
hypothesis-driven studies in order to examine the interrelationship of these
systems in the hope of better understanding IBD pathogenesis and to inform novel
therapies.
PMID- 27508056
TI - The effects of an editor serving as one of the reviewers during the peer-review
process.
AB - Background Publishing in scientific journals is one of the most important ways in
which scientists disseminate research to their peers and to the wider public. Pre
publication peer review underpins this process, but peer review is subject to
various criticisms and is under pressure from growth in the number of scientific
publications. Methods Here we examine an element of the editorial process at
eLife, in which the Reviewing Editor usually serves as one of the referees, to
see what effect this has on decision times, decision type, and the number of
citations. We analysed a dataset of 8,905 research submissions to eLife since
June 2012, of which 2,750 were sent for peer review, using R and Python to
perform the statistical analysis. Results The Reviewing Editor serving as one of
the peer reviewers results in faster decision times on average, with the time to
final decision ten days faster for accepted submissions (n=1,405) and 5 days
faster for papers that were rejected after peer review (n=1,099). There was no
effect on whether submissions were accepted or rejected, and a very small (but
significant) effect on citation rates for published articles where the Reviewing
Editor served as one of the peer reviewers. Conclusions An important aspect of
eLife's peer-review process is shown to be effective, given that decision times
are faster when the Reviewing Editor serves as a reviewer. Other journals hoping
to improve decision times could consider adopting a similar approach.
PMID- 27508057
TI - The expanding regulatory universe of p53 in gastrointestinal cancer.
AB - Tumor suppresser gene TP53 is one of the most frequently deleted or mutated genes
in gastrointestinal cancers. As a transcription factor, p53 regulates a number of
important protein coding genes to control cell cycle, cell death, DNA
damage/repair, stemness, differentiation and other key cellular functions. In
addition, p53 is also able to activate the expression of a number of small non
coding microRNAs (miRNAs) through direct binding to the promoter region of these
miRNAs. Many miRNAs have been identified to be potential tumor suppressors by
regulating key effecter target mRNAs. Our understanding of the regulatory network
of p53 has recently expanded to include long non-coding RNAs (lncRNAs). Like
miRNA, lncRNAs have been found to play important roles in cancer biology. With
our increased understanding of the important functions of these non-coding RNAs
and their relationship with p53, we are gaining exciting new insights into the
biology and function of cells in response to various growth environment changes.
In this review we summarize the current understanding of the ever expanding
involvement of non-coding RNAs in the p53 regulatory network and its implications
for our understanding of gastrointestinal cancer.
PMID- 27508058
TI - Can free open access resources strengthen knowledge-based emerging public health
priorities, policies and programs in Africa?
AB - Tackling emerging epidemics and infectious diseases burden in Africa requires
increasing unrestricted open access and free use or reuse of regional and global
policies reforms as well as timely communication capabilities and strategies.
Promoting, scaling up data and information sharing between African researchers
and international partners are of vital importance in accelerating open access at
no cost. Free Open Access (FOA) health data and information acceptability, uptake
tactics and sustainable mechanisms are urgently needed. These are critical in
establishing real time and effective knowledge or evidence-based translation,
proven and validated approaches, strategies and tools to strengthen and revamp
health systems. As such, early and timely access to needed emerging public
health information is meant to be instrumental and valuable for policy-makers,
implementers, care providers, researchers, health-related institutions and
stakeholders including populations when guiding health financing, and planning
contextual programs.
PMID- 27508059
TI - Early-childhood housing mobility and subsequent PTSD in adolescence: a Moving to
Opportunity reanalysis.
AB - In a 2014 report on adolescent mental health outcomes in the Moving to
Opportunity for Fair Housing Demonstration (MTO), Kessler et al. reported that,
at 10- to 15-year follow-up, boys from households randomized to an experimental
housing voucher intervention experienced 12-month prevalence of post-traumatic
stress disorder (PTSD) at several times the rate of boys from control households.
We reanalyze this finding here, bringing to light a PTSD outcome imputation
procedure used in the original analysis, but not described in the study report.
By bootstrapping with repeated draws from the frequentist sampling distribution
of the imputation model used by Kessler et al., and by varying two pseudorandom
number generator seeds that fed their analysis, we account for several purely
statistical components of the uncertainty inherent in their imputation procedure.
We also discuss other sources of uncertainty in this procedure that were not
accessible to a formal reanalysis.
PMID- 27508060
TI - search.bioPreprint: a discovery tool for cutting edge, preprint biomedical
research articles.
AB - The time it takes for a completed manuscript to be published traditionally can be
extremely lengthy. Article publication delay, which occurs in part due to
constraints associated with peer review, can prevent the timely dissemination of
critical and actionable data associated with new information on rare diseases or
developing health concerns such as Zika virus. Preprint servers are open access
online repositories housing preprint research articles that enable authors (1) to
make their research immediately and freely available and (2) to receive
commentary and peer review prior to journal submission. There is a growing
movement of preprint advocates aiming to change the current journal publication
and peer review system, proposing that preprints catalyze biomedical discovery,
support career advancement, and improve scientific communication. While the
number of articles submitted to and hosted by preprint servers are gradually
increasing, there has been no simple way to identify biomedical research
published in a preprint format, as they are not typically indexed and are only
discoverable by directly searching the specific preprint server websites. To
address this issue, we created a search engine that quickly compiles preprints
from disparate host repositories and provides a one-stop search solution.
Additionally, we developed a web application that bolsters the discovery of
preprints by enabling each and every word or phrase appearing to with articles
from preprint servers. This tool, search.bioPreprint, is publicly available at
http://www.hsls.pitt.edu/resources/preprint.
PMID- 27508061
TI - From reads to genes to pathways: differential expression analysis of RNA-Seq
experiments using Rsubread and the edgeR quasi-likelihood pipeline.
AB - In recent years, RNA sequencing (RNA-seq) has become a very widely used
technology for profiling gene expression. One of the most common aims of RNA-seq
profiling is to identify genes or molecular pathways that are differentially
expressed (DE) between two or more biological conditions. This article
demonstrates a computational workflow for the detection of DE genes and pathways
from RNA-seq data by providing a complete analysis of an RNA-seq experiment
profiling epithelial cell subsets in the mouse mammary gland. The workflow uses R
software packages from the open-source Bioconductor project and covers all steps
of the analysis pipeline, including alignment of read sequences, data
exploration, differential expression analysis, visualization and pathway
analysis. Read alignment and count quantification is conducted using the Rsubread
package and the statistical analyses are performed using the edgeR package. The
differential expression analysis uses the quasi-likelihood functionality of
edgeR.
PMID- 27508062
TI - Bioconductor workflow for microbiome data analysis: from raw reads to community
analyses.
AB - High-throughput sequencing of PCR-amplified taxonomic markers (like the 16S rRNA
gene) has enabled a new level of analysis of complex bacterial communities known
as microbiomes. Many tools exist to quantify and compare abundance levels or
microbial composition of communities in different conditions. The sequencing
reads have to be denoised and assigned to the closest taxa from a reference
database. Common approaches use a notion of 97% similarity and normalize the data
by subsampling to equalize library sizes. In this paper, we show that statistical
models allow more accurate abundance estimates. By providing a complete workflow
in R, we enable the user to do sophisticated downstream statistical analyses,
including both parameteric and nonparametric methods. We provide examples of
using the R packages dada2, phyloseq, DESeq2, ggplot2 and vegan to filter,
visualize and test microbiome data. We also provide examples of supervised
analyses using random forests, partial least squares and linear models as well as
nonparametric testing using community networks and the ggnetwork package.
PMID- 27508063
TI - Long noncoding RNAs in hematopoiesis.
AB - Mammalian development is under tight control to ensure precise gene expression.
Recent studies reveal a new layer of regulation of gene expression mediated by
long noncoding RNAs. These transcripts are longer than 200nt that do not have
functional protein coding capacity. Interestingly, many of these long noncoding
RNAs are expressed with high specificity in different types of cells, tissues,
and developmental stages in mammals, suggesting that they may have functional
roles in diverse biological processes. Here, we summarize recent findings of long
noncoding RNAs in hematopoiesis, which is one of the best-characterized mammalian
cell differentiation processes. Then we provide our own perspectives on future
studies of long noncoding RNAs in this field.
PMID- 27508064
TI - Recent advances in understanding cardiac contractility in health and disease.
AB - The aim of this review is to provide the reader with a synopsis of some of the
emerging ideas and experimental findings in cardiac physiology and
pathophysiology that were published in 2015. To provide context for the non
specialist, a brief summary of cardiac contraction and calcium (Ca) regulation in
the heart in health and disease is provided. Thereafter, some recently published
articles are introduced that indicate the current thinking on (1) the Ca
regulatory pathways modulated by Ca/calmodulin-dependent protein kinase II, (2)
the potential influences of nitrosylation by nitric oxide or S-nitrosated
proteins, (3) newly observed effects of reactive oxygen species (ROS) on
contraction and Ca regulation following myocardial infarction and a possible link
with changes in mitochondrial Ca, and (4) the effects of some of these signaling
pathways on late Na current and pro-arrhythmic afterdepolarizations as well as
the effects of transverse tubule disturbances.
PMID- 27508065
TI - Transporting mitochondria in neurons.
AB - Neurons demand vast and vacillating supplies of energy. As the key contributors
of this energy, as well as primary pools of calcium and signaling molecules,
mitochondria must be where the neuron needs them, when the neuron needs them. The
unique architecture and length of neurons, however, make them a complex system
for mitochondria to navigate. To add to this difficulty, mitochondria are
synthesized mainly in the soma, but must be transported as far as the distant
terminals of the neuron. Similarly, damaged mitochondria-which can cause
oxidative stress to the neuron-must fuse with healthy mitochondria to repair the
damage, return all the way back to the soma for disposal, or be eliminated at the
terminals. Increasing evidence suggests that the improper distribution of
mitochondria in neurons can lead to neurodegenerative and neuropsychiatric
disorders. Here, we will discuss the machinery and regulatory systems used to
properly distribute mitochondria in neurons, and how this knowledge has been
leveraged to better understand neurological dysfunction.
PMID- 27508067
TI - Homing in on the hepatic scar: recent advances in cell-specific targeting of
liver fibrosis.
AB - Despite the high prevalence of liver disease globally, there are currently no
approved anti-fibrotic therapies to treat patients with liver fibrosis. A major
goal in anti-fibrotic therapy is the development of drug delivery systems that
allow direct targeting of the major pro-scarring cell populations within the
liver (hepatic myofibroblasts) whilst not perturbing the homeostatic functions of
other mesenchymal cell types present within both the liver and other organ
systems. In this review we will outline some of the recent advances in our
understanding of myofibroblast biology, discussing both the origin of
myofibroblasts and possible myofibroblast fates during hepatic fibrosis
progression and resolution. We will then discuss the various strategies currently
being employed to increase the precision with which we deliver potential anti
fibrotic therapies to patients with liver fibrosis.
PMID- 27508066
TI - Genome-edited human stem cell-derived beta cells: a powerful tool for drilling
down on type 2 diabetes GWAS biology.
AB - Type 2 diabetes (T2D) is a disease of pandemic proportions, one defined by a
complex aetiological mix of genetic, epigenetic, environmental, and lifestyle
risk factors. Whilst the last decade of T2D genetic research has identified more
than 100 loci showing strong statistical association with disease susceptibility,
our inability to capitalise upon these signals reflects, in part, a lack of
appropriate human cell models for study. This review discusses the impact of two
complementary, state-of-the-art technologies on T2D genetic research: the
generation of stem cell-derived, endocrine pancreas-lineage cells and the editing
of their genomes. Such models facilitate investigation of diabetes-associated
genomic perturbations in a physiologically representative cell context and allow
the role of both developmental and adult islet dysfunction in T2D pathogenesis to
be investigated. Accordingly, we interrogate the role that patient-derived
induced pluripotent stem cell models are playing in understanding cellular
dysfunction in monogenic diabetes, and how site-specific nucleases such as the
clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system
are helping to confirm genes crucial to human endocrine pancreas development. We
also highlight the novel biology gleaned in the absence of patient lines,
including an ability to model the whole phenotypic spectrum of diabetes
phenotypes occurring both in utero and in adult cells, interrogating the non
coding 'islet regulome' for disease-causing perturbations, and understanding the
role of other islet cell types in aberrant glycaemia. This article aims to
reinforce the importance of investigating T2D signals in cell models reflecting
appropriate species, genomic context, developmental time point, and tissue type.
PMID- 27508068
TI - Neurobiology of opioid dependence in creating addiction vulnerability.
AB - Opioid drugs are potent modulators of many physiological and psychological
processes. When given acutely, they can elicit the signature responses of
euphoria and analgesia that societies have coveted for centuries. Repeated, or
chronic, use of opioids induces adaptive or allostatic changes that modify
neuronal circuitry and create an altered normality - the "drug-dependent" state.
This state, at least that exhibited by those maintained continuously on long
acting opioid drugs such as methadone or buprenorphine, is generally
indistinguishable from the drug-naive state for most overt behaviors. The
consequences of the allostatic changes (cellular, circuit, and system
adaptations) that accompany the drug-dependent state are revealed during drug
withdrawal. Drug cessation triggers a temporally orchestrated allostatic re
establishment of neuronal systems, which is manifested as opposing physiological
and psychological effects to those exhibited by acute drug intoxication. Some
withdrawal symptoms, such as physical symptoms (sweating, shaking, and diarrhea)
resolve within days, whilst others, such as dysphoria, insomnia, and anxiety, can
linger for months, and some adaptations, such as learned associations, may be
established for life. We will briefly discuss the cellular mechanisms and neural
circuitry that contribute to the opioid drug-dependent state, inferring an
emerging role for neuroinflammation. We will argue that opioid addictive
behaviors result from a learned relationship between opioids and relief from an
existing or withdrawal-induced anxiogenic and/or dysphoric state. Furthermore, a
future stressful life event can recall the memory that opioid drugs alleviate
negative affect (despair, sadness, and anxiety) and thereby precipitate craving,
resulting in relapse. A learned association of relief of aversive states would
fuel drug craving in vulnerable people living in an increasingly stressful
society. We suggest that this route to addiction is contributive to the current
opioid epidemic in the USA.
PMID- 27508069
TI - Regenerating the liver: not so simple after all?
AB - Under normal homeostatic conditions, hepatocyte renewal is a slow process and
complete turnover likely takes at least a year. Studies of hepatocyte
regeneration after a two-thirds partial hepatectomy (2/3 PH) have strongly
suggested that periportal hepatocytes are the driving force behind regenerative
re-population, but recent murine studies have brought greater complexity to the
issue. Although periportal hepatocytes are still considered pre-eminent in the
response to 2/3 PH, new studies suggest that normal homeostatic renewal is driven
by pericentral hepatocytes under the control of Wnts, while pericentral injury
provokes the clonal expansion of a subpopulation of periportal hepatocytes
expressing low levels of biliary duct genes such as Sox9 and osteopontin.
Furthermore, some clarity has been given to the debate on the ability of biliary
derived hepatic progenitor cells to generate physiologically meaningful numbers
of hepatocytes in injury models, demonstrating that under appropriate
circumstances these cells can re-populate the whole liver.
PMID- 27508070
TI - Gallstones: new insights into an old story.
AB - Gallstones, particularly cholesterol gallstones, are common in Western
populations and may cause symptoms such as biliary colic or complications such as
acute cholecystitis or gallstone pancreatitis. Recent studies have allowed for a
better understanding of the risk of symptoms or complications in patients with
gallstones. In addition, newer data suggest an association of gallstones with
overall mortality, cardiovascular disease, gastrointestinal cancers, and non
alcoholic fatty liver disease. Knowledge of appropriate indications and timing of
cholecystectomy, particularly for mild biliary pancreatitis, has gradually
accumulated. Lastly, there are exciting possibilities for novel agents to treat
or prevent cholesterol stone disease. This review covers new advances in our
understanding of the natural history, clinical associations, and management of
gallstone disease.
PMID- 27508071
TI - Varicocele - a case for early intervention.
AB - Testicular varicocele, which is defined as the dilation of the veins draining the
testicle, has long been associated with a detrimental effect on testicular
function. Despite a lack of high-quality, prospective data, recent evidence has
shed light on potential links between varicocele and male infertility and serum
testosterone levels. Similarly, varicocele repair has increasingly been shown to
have a beneficial impact on pregnancy rates, semen parameters, and on improving
serum testosterone in adult men. Numerous studies have assessed the optimal
technique for varicocele repair and the bulk of the evidence has shown the
microsurgical inguinal/subinguinal approach to have the highest success rates,
the lowest overall complication rates, and the lowest recurrence rates. The
management of varicocele in adolescents remains a clinical conundrum, but
contemporary evidence suggests early deleterious effects of varicocele on
testicular function in some patients. Well-designed prospective trials are
critical to delineate the true impact and role of varicocele repair on male
infertility and hypogonadism in adult and adolescent men.
PMID- 27508072
TI - Novel insights into mitotic chromosome condensation.
AB - The fidelity of mitosis is essential for life, and successful completion of this
process relies on drastic changes in chromosome organization at the onset of
nuclear division. The mechanisms that govern chromosome compaction at every cell
division cycle are still far from full comprehension, yet recent studies provide
novel insights into this problem, challenging classical views on mitotic
chromosome assembly. Here, we briefly introduce various models for chromosome
assembly and known factors involved in the condensation process (e.g. condensin
complexes and topoisomerase II). We will then focus on a few selected studies
that have recently brought novel insights into the mysterious way chromosomes are
condensed during nuclear division.
PMID- 27508073
TI - Horizontal gene transfer: essentiality and evolvability in prokaryotes, and roles
in evolutionary transitions.
AB - The wide spread of gene exchange and loss in the prokaryotic world has prompted
the concept of 'lateral genomics' to the point of an outright denial of the
relevance of phylogenetic trees for evolution. However, the pronounced coherence
congruence of the topologies of numerous gene trees, particularly those for
(nearly) universal genes, translates into the notion of a statistical tree of
life (STOL), which reflects a central trend of vertical evolution. The STOL can
be employed as a framework for reconstruction of the evolutionary processes in
the prokaryotic world. Quantitatively, however, horizontal gene transfer (HGT)
dominates microbial evolution, with the rate of gene gain and loss being
comparable to the rate of point mutations and much greater than the duplication
rate. Theoretical models of evolution suggest that HGT is essential for the
survival of microbial populations that otherwise deteriorate due to the Muller's
ratchet effect. Apparently, at least some bacteria and archaea evolved dedicated
vehicles for gene transfer that evolved from selfish elements such as plasmids
and viruses. Recent phylogenomic analyses suggest that episodes of massive HGT
were pivotal for the emergence of major groups of organisms such as multiple
archaeal phyla as well as eukaryotes. Similar analyses appear to indicate that,
in addition to donating hundreds of genes to the emerging eukaryotic lineage,
mitochondrial endosymbiosis severely curtailed HGT. These results shed new light
on the routes of evolutionary transitions, but caution is due given the inherent
uncertainty of deep phylogenies.
PMID- 27508074
TI - Tuning cell migration: contractility as an integrator of intracellular signals
from multiple cues.
AB - There has been immense progress in our understanding of the factors driving cell
migration in both two-dimensional and three-dimensional microenvironments over
the years. However, it is becoming increasingly evident that even though most
cells share many of the same signaling molecules, they rarely respond in the same
way to migration cues. To add to the complexity, cells are generally exposed to
multiple cues simultaneously, in the form of growth factors and/or physical cues
from the matrix. Understanding the mechanisms that modulate the intracellular
signals triggered by multiple cues remains a challenge. Here, we will focus on
the molecular mechanism involved in modulating cell migration, with a specific
focus on how cell contractility can mediate the crosstalk between signaling
initiated at cell-matrix adhesions and growth factor receptors.
PMID- 27508075
TI - Primary Hyperparathyroidism.
AB - Over the past several generations, primary hyperparathyroidism (PHTP) has
undergone a change in its clinical presentation in many countries from a
symptomatic disease to an asymptomatic one. The reasons for this change in
clinical presentation are related to the widespread use of biochemical screening
tests, to the measurement of PTH more routinely in the evaluation of metabolic
bone disease and to the status of vitamin D sufficiency in the population. Along
with recognition of a broader clinical spectrum of disease, including a more
recently recognized normocalcemic variant, has come an appreciation that the
evaluation of classic target organs that can be affected in PHPT, such as the
skeleton and the kidneys, require more advanced imaging technology for complete
evaluation. It is clear that even in asymptomatic patients, evidence for
microstructural disease in the skeleton and calcifications in the kidneys can be
demonstrated often. Potential non-classical manifestations of PHPT related to
neurocognition and the cardiovascular system continue to be of interest. As a
result of these advances, revised guidelines for the management of asymptomatic
PHPT have been recently published to help the clinician determine whether surgery
is appropriate or whether a more conservative approach is acceptable.
PMID- 27508076
TI - Advances of gene therapy for primary immunodeficiencies.
AB - In the recent past, the gene therapy field has witnessed a remarkable series of
successes, many of which have involved primary immunodeficiency diseases, such as
X-linked severe combined immunodeficiency, adenosine deaminase deficiency,
chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress
has widened the choice of therapeutic options in some specific cases of primary
immunodeficiency, much remains to be done to extend the geographical availability
of such an advanced approach and to increase the number of diseases that can be
targeted. At the same time, emerging technologies are stimulating intensive
investigations that may lead to the application of precise genetic editing as the
next form of gene therapy for these and other human genetic diseases.
PMID- 27508077
TI - Recent insights into the molecular mechanisms of the NLRP3 inflammasome
activation.
AB - Inflammasomes are high-molecular-weight protein complexes that are formed in the
cytosolic compartment in response to danger- or pathogen-associated molecular
patterns. These complexes enable activation of an inflammatory protease caspase
1, leading to a cell death process called pyroptosis and to proteolytic cleavage
and release of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Along
with caspase-1, inflammasome components include an adaptor protein, ASC, and a
sensor protein, which triggers the inflammasome assembly in response to a danger
signal. The inflammasome sensor proteins are pattern recognition receptors
belonging either to the NOD-like receptor (NLR) or to the AIM2-like receptor
family. While the molecular agonists that induce inflammasome formation by AIM2
and by several other NLRs have been identified, it is not well understood how the
NLR family member NLRP3 is activated. Given that NLRP3 activation is relevant to
a range of human pathological conditions, significant attempts are being made to
elucidate the molecular mechanism of this process. In this review, we summarize
the current knowledge on the molecular events that lead to activation of the
NLRP3 inflammasome in response to a range of K (+) efflux-inducing danger
signals. We also comment on the reported involvement of cytosolic Ca (2+) fluxes
on NLRP3 activation. We outline the recent advances in research on the
physiological and pharmacological mechanisms of regulation of NLRP3 responses,
and we point to several open questions regarding the current model of NLRP3
activation.
PMID- 27499850
TI - From hepatoprotection models to new therapeutic modalities for treating liver
diseases: a personal perspective.
AB - A variety of rodent models of hepatoprotection have been developed in which
tolerance to acetaminophen-induced hepatotoxicity occurs.
Autoprotection/heteroprotection is a phenomenon where prior exposure to a mildly
toxic dose of toxicant confers protection against a subsequently administered
higher dose of the same toxicant (as in the case of autoprotection) or to a
different toxicant (referred to as heteroprotection). Multiple mechanisms
regulate this adaptive response, including hepatocellular proliferation,
proteostasis, enhanced expression of cytoprotective genes, and altered tissue
immune response. In this review, we will discuss recent findings that highlight
the complexity of these adaptive mechanisms and we also outline the usefulness of
these findings to devise therapeutic and/or diagnostic tools for acetaminophen
induced liver damage in patients.
PMID- 27508079
TI - Higher reliability of triple-phase bone scintigraphy in cementless total hip
arthroplasty compared to cementless bipolar hemiarthroplasty.
AB - PURPOSE: Periprosthetic infection is one of the main reasons for revision surgery
after hip arthroplasty. The purpose of the present study is to compare the
reliability of triple-phase bone scintigraphy (TPBS) in the diagnosis of
periprosthetic infection between cementless total hip arthroplasty (THA) and
bipolar hemiarthroplasty (BHA). METHODS: In this retrospective study, 52 patients
were analyzed; 33 of them were performed with THA and 19 of them were performed
with BHA. The exclusion criteria were cementation in previous surgery,
romatological joint disorders, periprosthetic fracture and malignancy history. C
reactive protein (CRP) and erythrocyte sedimentation (ESR) rate results were
recorded preoperatively. Tissue samples from the different areas periprosthetic
tissue were obtained for histopathological examination and sample tissue culture.
RESULTS: In the present study, the sensitivity, specificity and accuracy were
90.9%, 77.3% and 81.8%, respectively, for THA and 77.8%, 60.0% and 68.4%,
respectively, for BHA. Positive predictive values for THA and BHA were 66.7% and
63.6%, and negative predictive values were 94.4% and 75.0%, respectively.
CONCLUSIONS: Due to the higher sensitivity, specificity and accuracy, TPBS has a
more reliable diagnostic value for cementless THA in the diagnosis of
periprosthetic infection compared to cementless BHA.
PMID- 27508080
TI - Extralevator abdominoperineal excision (Elape): A retrospective cohort study.
AB - INTRODUCTION: Extralevator abdominoperineal excision (ELAPE) is relatively new
surgical technique for low rectal cancers. It is a more radical approach than
conventional abdominoperineal excision (APE) with potentially better oncological
outcome. The aim of this study was to analyse short term results of ELAPE
compared with conventional abdominoperineal excision. METHODS: Data were
collected prospectively for 72 patients who underwent abdominoperineal excision
(APE) for low rectal carcinomas from 2010 to 2014. Of these 24 patients underwent
ELAPE with biological prosthetic mesh used to close the perineal defect. RESULTS:
The median age of patients was 68 (37-87). Positive circumferential resection
margin (1/24 vs. 8/48) and Intra operative perorations (0/24 vs. 6/48) compared
favourably with ELAPE. CONCLUSIONS: Short term results from this study support
that ELAPE has better oncological outcome.
PMID- 27508081
TI - Anxiety and depression on an acute respiratory ward.
AB - OBJECTIVES: Psychological difficulties are a common complication among patients
with respiratory disease, and are associated with poorer health outcomes and
increased use of healthcare. As prevalence studies typically sample patients from
community settings, this study aimed to explore the extent and nature of
psychological difficulties during acute hospital admission. METHODS: A case
example of an acute respiratory ward is presented. In total, 41 acute respiratory
inpatients completed standardised measures of depression, anxiety, and health
anxiety. RESULTS: Rates of clinically significant depression, anxiety, and health
anxiety were 71%, 40%, and 21%, respectively, with 76% of participants showing
clinically significant scores on at least one measure. Comparison to existing
literature suggests depression rates may be elevated in the acute inpatient
context. The difficulties experienced encompassed both contextual factors related
to being in hospital and broader health concerns. CONCLUSION: We suggest that
psychological distress may be particularly prevalent in inpatient settings and
that larger-scale studies are warranted.
PMID- 27508082
TI - Optimization of DRASTIC method by artificial neural network, nitrate
vulnerability index, and composite DRASTIC models to assess groundwater
vulnerability for unconfined aquifer of Shiraz Plain, Iran.
AB - BACKGROUND: Extensive human activities and unplanned land uses have put
groundwater resources of Shiraz plain at a high risk of nitrate pollution,
causing several environmental and human health issues. To address these issues,
water resources managers utilize groundwater vulnerability assessment and
determination of protection. This study aimed to prepare the vulnerability maps
of Shiraz aquifer by using Composite DRASTIC index, Nitrate Vulnerability index,
and artificial neural network and also to compare their efficiency. METHODS: The
parameters of the indexes that were employed in this study are: depth to water
table, net recharge, aquifer media, soil media, topography, impact of the vadose
zone, hydraulic conductivity, and land use. These parameters were rated,
weighted, and integrated using GIS, and then, used to develop the risk maps of
Shiraz aquifer. RESULTS: The results indicated that the southeastern part of the
aquifer was at the highest potential risk. Given the distribution of groundwater
nitrate concentrations from the wells in the underlying aquifer, the artificial
neural network model offered greater accuracy compared to the other two indexes.
The study concluded that the artificial neural network model is an effective
model to improve the DRASTIC index and provides a confident estimate of the
pollution risk. CONCLUSIONS: As intensive agricultural activities are the
dominant land use and water table is shallow in the vulnerable zones, optimized
irrigation techniques and a lower rate of fertilizers are suggested. The findings
of our study could be used as a scientific basis in future for sustainable
groundwater management in Shiraz plain.
PMID- 27508083
TI - A spectrum of CYP1B1 mutations associated with primary congenital glaucoma in
families of Pakistani descent.
AB - Glaucoma is the second leading cause of blindness, affecting ~65 million people
worldwide. We identified and ascertained a large cohort of inbred families with
multiple individuals manifesting cardinal symptoms of primary congenital glaucoma
(PCG) to investigate the etiology of the disease at a molecular level. Ophthalmic
examinations, including slit-lamp microscopy and applanation tonometry, were
performed to characterize the causal phenotype and confirm that affected
individuals fulfilled the diagnostic criteria for PCG. Subsequently, exclusion
analysis was completed with fluorescently labeled short tandem repeat markers,
followed by Sanger sequencing to identify pathogenic variants. Exclusion analysis
suggested linkage to the CYP1B1 locus, with positive two-point logarithm of odds
scores in 23 families, while Sanger sequencing identified a total of 11 variants,
including two novel mutations, in 23 families. All mutations segregated with the
disease phenotype in their respective families. These included the following
seven missense mutations: p.Y81N, p.E229K, p.R368H, p.R390H, p.W434R, p.R444Q and
p.R469W, as well as one nonsense mutation, p.Q37*, and three frameshift
mutations, p.W246Lfs81*, p.T404Sfs30* and p.P442Qfs15*. In conclusion, we
identified a total of 11 mutations, reconfirming the genetic heterogeneity of
CYP1B1 in the pathogenesis of PCG. To the best of our knowledge, this is the
largest study investigating the contribution of CYP1B1 to the pathogenesis of PCG
in the Pakistani population.
PMID- 27508084
TI - A novel nonsense mutation in the NOG gene causes familial NOG-related
symphalangism spectrum disorder.
AB - The human noggin (NOG) gene is responsible for a broad spectrum of clinical
manifestations of NOG-related symphalangism spectrum disorder (NOG-SSD), which
include proximal symphalangism, multiple synostoses, stapes ankylosis with broad
thumbs (SABTT), tarsal-carpal coalition syndrome, and brachydactyly type B2. Some
of these disorders exhibit phenotypes associated with congenital stapes
ankylosis. In the present study, we describe a Japanese pedigree with
dactylosymphysis and conductive hearing loss due to congenital stapes ankylosis.
The range of motion in her elbow joint was also restricted. The family showed
multiple clinical features and was diagnosed with SABTT. Sanger sequencing
analysis of the NOG gene in the family members revealed a novel heterozygous
nonsense mutation (c.397A>T; p.K133*). In the family, the prevalence of
dactylosymphysis and hyperopia was 100% while that of stapes ankylosis was less
than 100%. Stapes surgery using a CO2 laser led to a significant improvement of
the conductive hearing loss. This novel mutation expands our understanding of NOG
SSD from clinical and genetic perspectives.
PMID- 27508085
TI - Tuberculosis in foreign students in Japan, 2010-2014: a comparison with the
notification rates in their countries of origin.
PMID- 27508086
TI - Profile of tuberculosis among the foreign-born population in Japan, 2007-2014.
AB - The proportion of foreign-born people among the newly notified tuberculosis (TB)
patients has been increasing in recent years and potentially poses a new
challenge to TB control in Japan. In this report, we analysed the data from the
Japan TB surveillance system between 2007 and 2014 to gain an overview of the
trends and characteristics of foreign-born TB patients in Japan. We found that
the proportion of foreign-born TB patients was especially high among the younger
age groups - 44.1% among the 20-29 years age group in 2014. The largest groups of
foreign-born patients were from China and the Philippines; however, the number of
those from Nepal and Viet Nam was on the rise. Students comprised the second
largest professional category group for TB after regular workers, and its
proportion increased over the study period. Compared to Japan-born TB patients,
foreign-born patients were more likely to be diagnosed through routine medical
check-ups. Treatment successes and patients still on treatment were significantly
lower among foreign-born patients than their Japan-born counterparts; and
transferred-out and unknown outcomes were higher. Our results indicated that
distinctive subgroups within the foreign-born population in Japan, especially
students and regular workers, might have a higher risk of developing TB. Measures
to ensure early diagnosis and treatment adherence should be adapted to such
populations.
PMID- 27508087
TI - Assessment of the risk posed to Singapore by the 2015 Middle East respiratory
syndrome outbreak in the Republic of Korea.
AB - OBJECTIVE: To assess the public health risk to Singapore posed by the Middle East
respiratory syndrome (MERS) outbreak in the Republic of Korea in 2015. METHODS:
The likelihood of importation of MERS cases and the magnitude of the public
health impact in Singapore were assessed to determine overall risk. Literature on
the epidemiology and contextual factors associated with MERS coronavirus
infection was collected and reviewed. Connectivity between the Republic of Korea
and Singapore was analysed. Public health measures implemented by the two
countries were reviewed. RESULTS: The epidemiology of the 2015 MERS outbreak in
the Republic of Korea remained similar to the MERS outbreaks in Saudi Arabia. In
addition, strong infection control and response measures were effective in
controlling the outbreak. In view of the air traffic between Singapore and MERS
affected areas, importation of MERS cases into Singapore is possible.
Nonetheless, the risk of a serious public health impact to Singapore in the event
of an imported case of MERS would be mitigated by its strong health-care system
and established infection control practices. DISCUSSION: The MERS outbreak was
sparked by an exported case from the Middle East, which remains a concern as the
reservoir of infection (thought to be camels) continues to exist in the Middle
East, and sporadic cases in the community and outbreaks in health-care settings
continue to occur there. This risk assessment highlights the need for Singapore
to stay vigilant and to continue enhancing core public health capacities to
detect and respond to MERS coronavirus.
PMID- 27508088
TI - External quality assessment of dengue and chikungunya diagnostics in the Asia
Pacific region, 2015.
AB - OBJECTIVE: To conduct an external quality assessment (EQA) of dengue and
chikungunya diagnostics among national-level public health laboratories in the
Asia Pacific region following the first round of EQA for dengue diagnostics in
2013. METHODS: Twenty-four national-level public health laboratories performed
routine diagnostic assays on a proficiency testing panel consisting of two
modules. Module A contained serum samples spiked with cultured dengue virus
(DENV) or chikungunya virus (CHIKV) for the detection of nucleic acid and DENV
non-structural protein 1 (NS1) antigen. Module B contained human serum samples
for the detection of anti-DENV antibodies. RESULTS: Among 20 laboratories testing
Module A, 17 (85%) correctly detected DENV RNA by reverse transcription
polymerase chain reaction (RT-PCR), 18 (90%) correctly determined serotype and 19
(95%) correctly identified CHIKV by RT-PCR. Ten of 15 (66.7%) laboratories
performing NS1 antigen assays obtained the correct results. In Module B, 18/23
(78.3%) and 20/20 (100%) of laboratories correctly detected anti-DENV IgM and
IgG, respectively. Detection of acute/recent DENV infection by both molecular (RT
PCR) and serological methods (IgM) was available in 19/24 (79.2%) participating
laboratories. DISCUSSION: Accurate laboratory testing is a critical component of
dengue and chikungunya surveillance and control. This second round of EQA reveals
good proficiency in molecular and serological diagnostics of these diseases in
the Asia Pacific region. Further comprehensive diagnostic testing, including
testing for Zika virus, should comprise future iterations of the EQA.
PMID- 27508089
TI - Prevalence of resistance to second-line tuberculosis drug among multidrug
resistant tuberculosis patients in Viet Nam, 2011.
AB - INTRODUCTION: Extensively drug-resistant tuberculosis (XDR-TB) represents an
emerging public health problem worldwide. According to the World Health
Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are
defined as XDR-TB globally. The objective of this study was to determine the
prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected
in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam.
METHODS: Eighty clusters of TB cases were selected using a probability-proportion
to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was
performed for the four major first-line TB drugs. DST of second-line drugs
(ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR
TB cases to identify pre-XDR and XDR cases. RESULTS: A total of 1629 smear
positive TB cases were eligible for culture and DST. Of those, DST results for
first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second
line DST results were available for 84 of these cases. Of those, 15 cases (17.9%)
had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin.
Five MDR-TB cases (6.0%) met the criteria of XDR-TB. CONCLUSION: This survey
provides the first estimates of the proportion of XDR-TB among MDR-TB cases in
Viet Nam and provides important information for local policies regarding second
line DST. Local policies and programmes that are geared towards TB prevention,
early diagnosis and treatment with effective regimens are of high importance.
PMID- 27508090
TI - Epidemiology and control of tuberculosis in the Western Pacific Region: update
with 2013 case notification data.
AB - INTRODUCTION: Since the year 2000, tuberculosis (TB) prevalence in the World
Health Organization (WHO) Western Pacific Region decreased 36%. However, there
were an estimated 1.6 million TB cases in the Region in 2013. This study
describes a regional analysis using the WHO global TB database data from 2000 to
2013. METHODS: TB surveillance data are annually collected from 36 countries and
areas in the Western Pacific Region using a web-based system. TB case
notifications, treatment outcomes and information on TB/HIV coinfection are
analysed descriptively. Stratified analysis of the TB data by age, sex and
countries and areas were conducted. RESULTS: Countries and areas in the Western
Pacific Region notified 1.3 million new and relapse TB cases in 2013. TB
notification rate increased in the early 2000s, stabilized for several years and
declined recently. Country-specific TB notification rates declined over time for
all age groups in most countries. TB treatment success rates remain high in the
Region with 16 countries reaching or maintaining 85% (or higher) in 2013. HIV
testing among TB cases has increased gradually with approximately 11 000 HIV
positive TB cases diagnosed each year since 2009. DISCUSSION: The results suggest
that true TB incidence is possibly declining. Treatment success rates have
remained high for six of seven high-burden countries. TB surveillance data
analysis is an important source of programmatic and epidemiological information.
Careful interpretation of these findings can provide useful insight for
programmatic decision-making. While the TB burden remains immense, national TB
programmes must evolve and adapt to build upon previous efforts.
PMID- 27508092
TI - Celecoxib-erlotinib combination delays growth and inhibits angiogenesis in EGFR
mutated lung cancer.
AB - Combination treatment for non-small cell lung cancer (NSCLC) is becoming more
popular due to the anticipation that it may be more effective than single drug
treatment. In addition, there are efforts to genetically screen patients for
specific mutations in light of attempting to administer specific anticancer
agents that are most effective. In this study, we evaluate the anticancer and
anti-angiogenic effects of low dose celecoxib-erlotinib combination in NSCLC in
vitro and in vivo. In NSCLC cells harboring epidermal growth factor receptor
(EGFR) mutations, combination celecoxib-erlotinib treatment led to synergistic
cell death, but there was minimal efficacy in NSCLC cells with wild-type EGFR. In
xenograft models, combination treatment also demonstrated greater inhibition of
tumor growth compared to individual treatment. The anti-tumor effect observed was
secondary to the targeting of angiogenesis, evidenced by decreased vascular
endothelial growth factor A (VEGFA) levels and decreased levels of CD31 and
microvessel density. Combination treatment targets angiogenesis through the
modulation of of the PI3K/AKT and ERK/Raf1-1 pathway in NSCLC with EGFR exon 19
deletions. These findings may have significant clinical implications in patients
with tumors harboring EGFR exon 19 deletions as they may be particularly
sensitive to this regimen.
PMID- 27508091
TI - Extracellular MicroRNA in liquid biopsy: applicability in cancer diagnosis and
prevention.
AB - One of the goals of contemporary cancer research is the development of new
markers that facilitate earlier and non-invasive diagnosis. MicroRNAs are non
coding RNA molecules that regulate gene expression; studies have shown that their
expression levels are altered in cancer. Recently, extra-cellular microRNAs have
been detected in biological fluids and studied as possible cancer markers that
can be detected by noninvasive procedures. In this review, we analyze the current
understanding of extracellular miRNAs based on clinical studies to establish
their possible use for the prevention of the most common tumors. Despite
discrepancies among different studies of the same cancers, panels of specific
extracellular microRNAs are emerging as a new tool for the secondary (selection
of high-risk individuals to undergo screening) and tertiary (relapse) prevention
of cancer.
PMID- 27508093
TI - Circulating miR-21 as an independent predictive biomarker for chemoresistance in
esophageal squamous cell carcinoma.
AB - Only a few studies indentified the significance of circulating microRNAs in blood
as a predictive biomarker for chemoresistance in esophageal squamous cell
carcinoma (ESCC). In this study, we tested whether oncogenic miR-21 promoted
chemoresistance in ESCC and served as a biomarker for predicting chemoresistance
in plasma of patients with ESCC. All consecutive patients underwent the
preoperative chemotherapy regimen (JCOG9907 trial) with cisplatin plus 5
fluorouracil. As a result, pretreatment plasma concentrations of miR-21 were
significantly higher in ESCC patients with a low histopathological response than
in those with a high histopathological response (P = 0.0416). Multivariate
analysis revealed that a high pretreatment plasma concentration of miR-21 was an
independent risk factor of chemoresistance (p = 0.0150; Odds Ratio 9.95 (range:
1.56-63.4)). The expression of miR-21 was also significantly higher in
pretreatment ESCC tissues with a low histopathological response than in those
with a high histopathological response (P = 0.0409). In vitro, although the
growth of KYSE 170 ESCC cells transfected with the control mimics was markedly
inhibited by the 5-fluorouracil or cisplatin treatment, the inhibitory effects of
5-FU (P < 0.05) or cisplatin (P < 0.05) were significantly reduced in KYSE170
cells that overexpressed miR-21. Taken together, the overexpression of miR-21
contributed to chemoresistance and circulating miR-21 in plasma of patients with
ESCC could be a useful biomarker for predicting chemoresistance.
PMID- 27508094
TI - TMEM45A, SERPINB5 and p16INK4A transcript levels are predictive for development
of high-grade cervical lesions.
AB - Women persistently infected with human papillomavirus (HPV) type 16 are at high
risk for development of cervical intraepithelial neoplasia grade 3 or cervical
cancer (CIN3+). We aimed to identify biomarkers for progression to CIN3+ in women
with persistent HPV16 infection. In this prospective study, 11,088 women aged 20
29 years were enrolled during 1991-1993, and re-invited for a second visit two
years later. Cervical cytology samples obtained at both visits were tested for
HPV DNA by Hybrid Capture 2 (HC2), and HC2-positive samples were genotyped by
INNO-LiPA. The cohort was followed for up to 19 years via a national pathology
register. To identify markers for progression to CIN3+, we performed microarray
analysis on RNA extracted from cervical swabs of 30 women with persistent HPV16
infection and 11 HPV-negative women. Six genes were selected and validated by
quantitative PCR. Three genes were subsequently validated within a different and
large group of women from the same cohort. Secondly, Kaplan-Meier and Cox
regression analyses were used to investigate whether expression levels of those
three genes predict progression to CIN3+. We found that high transcript levels of
TMEM45A, SERPINB5 and p16INK4a at baseline were associated with increased risk of
CIN3+ during follow-up. The hazard ratios of CIN3+ per 10-fold increase in
baseline expression level were 1.6 (95% CI: 1.1-2.3) for TMEM45A, 1.6 (95% CI:
1.1-2.5) for p16INK4a, and 1.8 (95% CI: 1.2-2.7) for SERPINB5. In conclusion,
high mRNA expression levels of TMEM45A, SERPINB5 and p16INK4a were associated
with increased risk of CIN3+ in persistently HPV16-infected women.
PMID- 27508095
TI - MicroRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p as predictive markers of oral
leukoplakia that progress to cancer.
AB - Leukoplakia is the most common precursor lesion of oral squamous cell carcinoma
(OSCC). Currently, the risk of progression to OSCC is assessed based on
histopathologic examination alone. However, this method fails to identify the
subset of microscopically innocuous leukoplakia that ultimately transforms to
OSCC. The aim of this study was to determine if microRNAs (miRNAs) can be
utilized to identify non- and low-grade dysplastic oral lesions at risk for
cancer progression. A retrospective study of genome-wide miRNA expression level
analyses was performed in the training cohort (n=20) using deep sequencing
formalin-fixed paraffin embedded incisional biopsy tissues from patients with
oral leukoplakic lesions diagnosed with non- or low-grade dysplasia and known
clinical outcome. The promising miRNA candidates were then evaluated in the
validation cohort (n=80) using quantitative real-time PCR (qRT-PCR). Four
promising miRNAs-208b-3p, 204-5p, 129-2-3p and 3065-5p were identified. Combining
these four miRNAs as a panel with age and histologic diagnosis (p<0.004), our
final model had a predictive value for the area under the receiver operating
characteristic (ROC) curve (AUC) of 0.792, sensitivity of 76.9% and specificity
of 73.7% to accurately identify non- and low-grade dysplastic lesions at risk of
cancer progression, which is a significant improvement over histopathologic
examination alone (AUC of 0.645). While further investigation is needed,
discovery of predictive markers that can accurately identify histologically
innocuous oral lesions at high risk for progression to OSSC will significantly
improve clinical outcome by means of early intervention.
PMID- 27508096
TI - Response to 'Dai W et al. Am J Cancer Res 2015;5(10):3270-3275' from the makers
of nintedanib.
PMID- 27508097
TI - MicroRNA-17/20a impedes migration and invasion via TGF-beta/ITGB6 pathway in
esophageal squamous cell carcinoma.
AB - Patients with esophageal squamous cell carcinoma (ESCC) have an overall poor
prognosis due to invasion and metastasis. Although it has been studied
extensively, the metastatic mechanisms of ESCC remains largely unclear. Here, we
evaluated microRNA expression in ESCC cell sublines with distinct motility and
found that microRNA-17 and microRNA-20a (miR-17/20a) dramatically impeded cell
migration and invasion of ESCC in vitro and decreased pulmonary arrest in vivo.
Furthermore, we identified that TGF-beta receptor 2 (TGFBR2) and Smad anchor for
receptor activation (SARA) served as genuine miR-17/20a targets, which are both
implicated in TGF-beta pathway. TGF-beta treatment promoted the motility of ESCC
cells, and miR-17/20a could attenuate the activation of TGF-beta pathway by
weakening the phosphorylation of Smad2/3 to reduce the expression of ITGB6, which
was crucial in migration and invasion of ESCC cells. Moreover, evaluation of ESCC
specimens revealed a close correlation between miR-17/20a, TGFBR2, SARA and lymph
node metastasis. Together, our findings demonstrate that miR-17/20a suppresses
cell migration and invasion of ESCC by modulating TGF-beta/ITGB6 pathway,
suggesting a promising strategy for diagnosis and therapy of ESCC invasion and
metastasis.
PMID- 27508098
TI - MiR-153 promotes breast cancer cell apoptosis by targeting HECTD3.
AB - Homologous to the E6-associated protein carboxyl terminus domain containing 3
(HECTD3) is an E3 ubiquitin ligase which ubiquitinates caspase-8, caspase-9 and
promotes cancer cell survival. Aberrant HECTD3 expression is frequently involved
in various types of cancer progression. However, to date, the regulation of
HECTD3 remains unclear. Here, we demonstrated that miR-153 functions as a
negative regulator of HECTD3 and sensitizes cisplatin-induced apoptosis in triple
negative breast cancer cells MDA-MB-231 and BT-549. Luciferase reporter assay
demonstrated that miR-153 suppresses HECTD3 expression through directly targeting
its mRNA within the 3'-Untranslated Region (3'UTR). Additionally, the expression
levels of miR-153 and HECTD3 are inversely correlated in breast cancer cell
lines. Furthermore, ectopic expression of miR-153 promotes apoptosis in MDA-MB
231 and BT-549 cells treated with cisplatin or TNF-alpha, and miR-153 inhibitor
treatment inhibits cisplatin induced apoptosis in MDA-MB-231 and BT-549 cells.
Moreover, stable overexpression of HECTD3 abrogates the sensitization effect of
miR-153 to cisplatin treatment in MDA-MB-231 cells, and miR-153 inhibitor
protects cells against cisplatin cytotoxicity in control cells, but not in the
stable knockdown HECTD3 MDA-MB-231 cells. More importantly, breast cancer
patients with higher expression levels of miR-153 had significant higher 5-year
survival rate in PROGmiR database (P<0.05). Taken together, our study indicated
that miR-153 inhibits TNBC survival by targeting HECTD3 and functions as a potent
tumor suppressor.
PMID- 27508099
TI - Impacts of physically active and under-active on clinical outcomes of esophageal
cancer patients undergoing esophagectomy.
AB - Physical activity has been reported to positively influence quality of life and
survival in certain cancers. However, the associations between them in esophageal
cancer are previously undefined. The aims of this study are to investigate
whether physically active esophageal cancer patients have improved quality of
life and lower risk of recurrence as well as death compared with physically
inactive patients. We evaluated the relationships between postoperative leisure
time physical activity and quality of life and recurrence and death among
patients diagnosed with esophageal cancer. We respectively used generalized
estimating equations and Cox proportional regression to analysis quality of life
and survival, adjusting for known potential confounding factors. Comparing
esophageal cancer patients reporting more than 9 MET hours per week of
postoperative leisure time physical activity with those reporting less, we found
improved quality of life. Additionally, we also found that postoperative leisure
time physical activity >=9 MET hours per week, compared with less, was associated
with a 23% lower risk of all-cause mortality (HR, 0.666; 95% CI, 0.481-0.921;
P=0.014) and a 53% lower risk of recurrence (HR, 0.306; 95% CI 0.218-0.429;
P<0.001). Leisure time physical activity was significantly associated with
quality of life and risk of recurrence and death of esophageal cancer patients.
Clinicians should consider increasing physical activity, regardless of previous
behaviors, as a part of primary cancer treatment. The ultimate goal is to improve
quality of life and prolong survival of cancer survivors.
PMID- 27508100
TI - Erratum: MicroRNA-338-3p suppresses metastasis of lung cancer cells by targeting
the EMT regulator Sox4.
AB - [This corrects the article on p. 127 in vol. 6, PMID: 27186391.].
PMID- 27508101
TI - Invasive Meningococcal Meningitis Serogroup C Outbreak in Northwest Nigeria, 2015
- Third Consecutive Outbreak of a New Strain.
AB - BACKGROUND: In northwest Nigeria in 2013 and 2014, two sequential, localized
outbreaks of meningitis were caused by a new strain of Neisseria meningitidis
serogroup C (NmC). In 2015, an outbreak caused by the same novel NmC strain
occurred over a wider geographical area, displaying different characteristics to
the previous outbreaks. We describe cases treated by Medecins Sans Frontieres
(MSF) in the 2015 outbreak. METHODS: From February 10 to June 8, 2015, data on
cerebrospinal meningitis (CSM) cases and deaths were recorded on standardized
line-lists from case management sites supported by MSF. Cerebrospinal fluid (CSF)
samples from suspected cases at the beginning of the outbreak and throughout from
suspected cases from new geographical areas were tested using rapid Pastorex(r)
latex agglutination to determine causative serogroup. A subset of CSF samples was
also inoculated into Trans-Isolate medium for testing by the WHO Collaborating
Centre for Reference and Research on Meningococci, Oslo. Reactive vaccination
campaigns with meningococcal ACWY polysaccharide vaccine targeted affected
administrative wards. RESULTS: A total of 6394 (65 confirmed and 6329 probable)
cases of CSM including 321 deaths (case fatality rate: 5.0%) were recorded. The
cumulative attack rate was 282 cases per 100,000 population in the wards
affected. The outbreak lasted 17 weeks, affecting 1039 villages in 21 local
government areas in three states (Kebbi, Sokoto, Niger). Pastorex(r) tests were
NmC positive for 65 (58%) of 113 CSF samples. Of 31 Trans-Isolate medium samples,
26 (84%) tested positive for NmC (14 through culture and 12 through PCR); all had
the same rare PorA type P1.21-15,16 as isolates from the 2013 and 2014 outbreaks.
All 14 culture-positive samples yielded isolates of the same genotype (ST-10217
PorA type P1.21-15,16 and FetA type F1-7). More than 222,000 targeted individuals
were vaccinated relatively early in the outbreak (administrative coverage
estimates 98% and 89% in Kebbi and Sokoto, respectively). CONCLUSIONS: The
outbreak was the largest caused by NmC documented in Nigeria. Reactive
vaccination in both states may have helped curtail the epidemic. A vaccination
campaign against NmC with a long-lasting conjugate vaccine should be considered
in the region.
PMID- 27508102
TI - Long-term quality assurance of [(18)F]-fluorodeoxyglucose (FDG) manufacturing.
AB - Nine years of experience with 2286 commercial synthesis allowed us to deliver
comprehensive information on the quality of (18)F-FDG production. Semi-automated
FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG
synthesiser (GE Health, USA) using alkalic hydrolysis, grade "A" isolator with
dispensing robotic unit (Tema Sinergie, Italy), and automatic control system
under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable
aseptic production line, fully compliant with Good Manufacturing Practice and
just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in
steady yield and of very high radioactive purity. Synthesis yields exhibited high
variance connected probably with quality of disposable cassettes and chemicals
sets. Most performance non-conformities within the manufacturing cycle occur at
mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial
synthesis indicated high reliability of automatic synthesizers. Shewhart chart
and ANOVA analysis showed that minor non-compliances occurred were mostly caused
by the declinations of less experienced staff from standard operation procedures,
and also by quality of automatic cassettes. Only 15 syntheses were found
unfinished and in 4 cases the product was out-of-specification of European
Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling
in grade "A" isolator. Its cleanliness and sterility was fully controlled under
the investigated period by applying hydrogen peroxide vapours (VHP). Our
experience with quality assurance in the production of [(18)F]-fluorodeoxyglucose
(FDG) at production facility of BIONT based on TRACERlab MXFDG production module
can be used for bench-marking of the emerging manufacturing and automated
manufacturing systems.
PMID- 27508103
TI - A preliminary investigation into textural features of intratumoral metabolic
heterogeneity in (18)F-FDG PET for overall survival prognosis in patients with
bulky cervical cancer treated with definitive concurrent chemoradiotherapy.
AB - We examined the role of intratumoral metabolic heterogeneity on (18)F-FDG PET
during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for
patients with cervical cancer. This prospective study consisted of 44 patients
with bulky (>= 4 cm) cervical cancer treated with CCRT. All patients underwent
serial (18)F-FDG PET studies. Primary cervical tumor standardized uptake values,
metabolic tumor volume, and total lesion glycolysis (TLG) were measured in
pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features
were analyzed using the grey level run length encoding method (GLRLM) and grey
level size zone matrix. Associations between PET parameters and overall survival
(OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate
analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural
analysis and intra-treatment decline of run length nonuniformity < 55% and the
decline of TLG (?TLG) < 60% were associated with significantly worse OS. In
multivariate analysis, only ?TLG was significant (P = 0.009). Combining
pretreatment with intra-treatment factors, we defined the patients with a initial
GLNU > 48 and a ?TLG <= 60% as the high-risk group and the other patients as the
low-risk. The 5-year OS rate for the high-risk group was significantly worse than
that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The
heterogeneity of intratumoral FDG distribution and the early temporal change in
TLG may be an important predictor for OS in patients with bulky cervical cancer.
This gives the opportunity to adjust individualized regimens early in the
treatment course.
PMID- 27508104
TI - Design, construction and testing of a low-cost automated (68)Gallium-labeling
synthesis unit for clinical use.
AB - The interest in (68)Gallium labeled PET probes continues to increase around the
world. Widespread use in Europe and Asia has led to great interest for use at
numerous sites in the US. One barrier to entry is the cost of the automated
synthesis units for relatively simple labeling procedures. We describe the
construction and testing of a relatively low-cost automated (68)Ga-labeling unit
for human-use. We provide a guide for construction, including part lists and
synthesis timelists to facilitate local implementation. Such inexpensive systems
could help increase use around the globe and in the US in particular by removing
one of the barriers to greater widespread availability. The developed automated
synthesis unit reproducibly synthesized (68)Ga-DOTATOC with average yield of 71
+/- 8% and a radiochemical purity >= 95% in a synthesis time of 25 +/- 1 minutes.
Automated product yields are comparable to that of manual synthesis. We
demonstrate in-house construction and use of a low-cost automated synthesis unit
for labeling of DOTATOC and similar peptides with (68)Gallium.
PMID- 27508105
TI - Synthesis and pre-clinical evaluation of an (18)F-labeled single-chain antibody
fragment for PET imaging of epithelial ovarian cancer.
AB - Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed
antigen in the serum of patients who are under surveillance for epithelial
ovarian cancer (EOC). However, there is currently no molecular imaging probe in
the clinic for the assessment of CA125 expression in vivo. The present study
describes the development of an (18)F-labeled single-chain variable fragment
(scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was
derived from MAb-B43.13 by recombinant expression of the fragment in E.coli.
Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography
and characterized for antigen binding via immuno-staining and flow cytometry.
Prosthetic group N-succinimidyl 4-[(18)F]fluorobenzoate ([(18)F]SFB) was used for
radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed
based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125
negative) in NIH-III mice. The radiopharmacological profile of (18)F-labeled scFv
B43.13 ([(18)F]FBz-scFv-B43.13) was studied with PET. [(18)F]FBz-scFv-B43.13 was
prepared in radiochemical yields of 3.7 +/- 1.8% (n = 5) at an effective specific
activity of 3.88 +/- 0.76 GBq/umol (n = 5). The radiotracer demonstrated
selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125
negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in
OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post
injection (p.i.).
PMID- 27508106
TI - Development of a novel linearly-filled Derenzo microPET phantom.
AB - Positron emission tomography (PET) phantoms are used to calibrate PET scanners so
that inter-scanner and inter-isotope comparison can be made between PET datasets.
Hot rod style phantoms have a hole pattern, which is filled with a positron
emitting isotope and typically involves using two radioisotope reservoirs with
the pattern created with channels in between. However, this configuration is
difficult to fill and requires an excess of activity and volume. Here we present
an alternative design, a phantom that is linearly filled-one channel at a time.
The process of fabrication of prototypes of the design is described and PET
images of the prototyped phantom are also shown for a variety of commonly used
radioisotopes ((52)Mn, (64)Cu, (76)Br, (124)I). This design allows for a large
reduction in isotope volume and required filling time making a quality assurance
(QA) protocol safer, more efficient and less costly.
PMID- 27508107
TI - Novel melanoma therapy.
AB - With the rapid succession of new effective agents for melanoma in the recent
years, the paradigm for treatment of metastatic melanoma is changing. The success
of combining multiple effective agents compared with outcomes of monotherapy also
brings increasing complexity in the treatment algorithm for various subsets of
metastatic melanoma patients. We reviewed the recent reports on novel melanoma
therapy to shed light on rational decision-making in treating these patients.
PMID- 27508109
TI - Fundamental role of pan-inflammation and oxidative-nitrosative pathways in
neuropathogenesis of Alzheimer's disease [Retraction].
AB - [This retracts the article on p. 1 in vol. 5, PMID: 27073740.].
PMID- 27508108
TI - Non-invasive urine testing of EGFR activating mutation and T790M resistance
mutation in non-small cell lung cancer.
AB - BACKGROUND: The increasing understanding of non-small cell lung cancer (NSCLC)
biology over the last two decades has led to the identification of multiple
molecular targets. This led to the development of multiple targeted therapies in
the primary and secondary resistance setting and the epidermal growth factor
receptor (EGFR) gene remains the most frequently observed molecular target in
NSCLC. Tissue biopsies remain the standard for the identification of such EGFR
mutations. Obtaining serial tissue biopsies, especially in the secondary
resistance setting is associated with multiple medical and logistical challenges.
Utilizing circulating tumor DNA (ctDNA) fragments for molecular analysis can
overcome these challenges and aid in therapeutic decision-making. CASE
PRESENTATION: Here we present a present a 72-year-old Korean woman with
metastatic, EGFR L858R mutated bronchogenic adenocarcinoma. She developed
skeletal progression on treatment with first and second generation tyrosine
kinase inhibitors (TKIs). Repeated biopsies failed to provide informative
molecular test results. A novel urine ctDNA assay was utilized and confirmed
T790M positive status. The patient was started on a third generation TKI, which
led to a measurable clinical response. CONCLUSIONS: Utilization of urine liquid
biopsies for EGFR diagnostics are feasible and provided critical clinical
information in this patient's case. Urine liquid biopsy represents a viable
alternative to tissue biopsy, particularly in the secondary resistance setting,
when tissue is not available for molecular testing.
PMID- 27508110
TI - Omental transplantation in a patient with mild ALS.
AB - To demonstrate that amyotrophic lateral sclerosis (ALS) is not a
neurodegenerative disease. The patient, a 33-year-old man began with symptoms of
the bulbar form of ALS, characterized by burning pain in both feet during two
months and then, he presented right crural monoparesis, fasciculations, slight
dysarthria and he walked with help of orthopedic devices. A preoperative MRI
scans showed atherosclerosis at the V4 segment of the left vertebral artery. On
May 2012, he received an omental transplantation on the anterior, left lateral
and posterior surface of the medulla oblongata. About 48 hours after surgery, the
dysarthria disappeared and the voluntary movement of the right foot improved.
Three days later, he walked without aid of orthopedic device. At present, four
years after operation he present complete reversal of symptoms. In conclusion,
this patient confirms that bulbar ALS is of ischemic origin and therefore, mild
ALS can be cured.
PMID- 27508111
TI - Effect of probiotic and prebiotic fermented milk on skin and intestinal
conditions in healthy young female students.
AB - Although persistent constipation is considered to be associated with skin
problems, the supporting evidence is limited. Hence, this study investigated the
effects of probiotic and prebiotic fermented milk on skin and intestinal
conditions in an open-label trial. Among the 101 Japanese healthy young female
students that participated, the 81 subjects in the intake group consumed a bottle
of probiotic and prebiotic fermented milk containing Bifidobacterium breve strain
Yakult and galactooligosaccharides daily for 4 weeks after a pre-intake period of
4 weeks, while the 20 subjects in the non-intake group did not consume the test
beverage. Defecation patterns, skin conditions including hydration levels in the
stratum corneum, and urinary phenol and p-cresol levels were evaluated before
(baseline) and after intake. All subjects completed the study. No differences in
dietary intake and body mass index were observed between both groups during the
trial. In the intake group, hydration levels of the stratum corneum, defecation
frequency, and feces quantity significantly increased, and urinary phenol and p
cresol levels significantly decreased after intake compared with the
corresponding baseline values. However, they did not significantly change in the
non-intake group. A significant difference was observed between the intake group
and non-intake group in regard to clearness of the skin as assessed by visual
analogue scale. Therefore, consecutive intake of probiotic and prebiotic
fermented milk might have beneficial effects on the skin that prevent dryness and
beneficial effects on the intestinal conditions that stimulate defecation and
decrease phenol production by gut bacteria in healthy young women.
PMID- 27508112
TI - The production of S-equol from daidzein is associated with a cluster of three
genes in Eggerthella sp. YY7918.
AB - Daidzein (DZN) is converted to equol (EQL) by intestinal bacteria. We previously
reported that Eggerthella sp. YY7918, which is found in human feces, is an EQL
producing bacterium and analyzed its whole genomic sequence. We found three
coding sequences (CDSs) in this bacterium that showed 99% similarity to the EQL
producing enzymes of Lactococcus sp. 20-92. These identified CDSs were designated
eqlA, eqlB, and eqlC and thought to encode daidzein reductase (DZNR),
dihydrodaidzein reductase (DHDR), and tetrahydrodaidzein reductase (THDR),
respectively. These genes were cloned into pColdII. Recombinant plasmids were
then introduced into Escherichia coli BL21 (DE3) and DZNR, DHDR, and THDR were
expressed and purified by 6*His-Tag chromatography. We confirmed that these three
enzymes were involved in the conversion of DZN to EQL. Purified DZNR converted
DZN to dihydrodaizein (DHD) in the presence of NADPH. DHDR converted DHD to
tetrahydrodaizein (THD) in the presence of NADPH. Neither enzyme showed
activities with NADH. THDR converted THD in the absence of cofactors, NAD(P)H,
and also produced DHD as a by-product. Thus, we propose that THDR is not a
reductase but a new type of dismutase. The GC content of these clusters was 64%,
similar to the overall genomic GC content for Eggerthella and Coriobacteriaceae
(56-60%), and higher than that for Lactococcus garvieae (39%), even though the
gene cluster showed 99% similarity to that in Lactococcus sp. 20-92. Taken
together, our results indicate that the gene cluster associated with EQL
production evolved in high-GC bacteria including Coriobacteriaceae and was then
laterally transferred to Lactococcus sp. 20-92.
PMID- 27508113
TI - Safety and long-term effect of the probiotic FK-23 in patients with hepatitis C
virus infection.
AB - A clinical trial was conducted on 39 adult HCV-positive subjects to determine the
safety and long-term effect of the probiotic FK-23 (heat-treated Enterococcus
faecalis strain FK-23). Asymptomatic anti-HCV positive adults who fulfilled the
selection criteria and gave voluntary consent were recruited from attendees of
the Hepatitis Carrier Clinic, Department of Medical Research (Lower Myanmar).
Each subject was given 2,700 mg of FK-23 per day by oral route. Blood samples
were taken at enrollment and every 3 months and tested for alanine
aminotransferase (ALT) and aspartate transaminase (AST). Viral load, urea, total
protein, hemoglobin and platelet count were determined every 6 months. Among the
subjects, 23 completed 36 months, 31 completed 24 months, 35 completed 12 months
and 37 completed 6 months of probiotic therapy. Significant decreases in mean ALT
levels were observed at 3 months (34. 9 +/- 15.1 IU/l) as compared with the
initial level (64.8 +/- 17.5 IU/l) and persisted up to 36 months (43.7 +/- 25.2
IU/l). Decrease of AST was detected after 9 months (46.2 +/- 21.7 IU/l) of
probiotic therapy as compared with the initial level (64.3 +/- 28.7 IU/l). FK-23
was safe based on the stable levels of biochemical and hematological parameters
and the absence of untoward side effects. The FK-23 preparation was well
tolerated and accepted by the subjects.
PMID- 27508114
TI - Effect of consuming a purple-fleshed sweet potato beverage on health-related
biomarkers and safety parameters in Caucasian subjects with elevated levels of
blood pressure and liver function biomarkers: a 4-week, open-label, non
comparative trial.
AB - An open-label study with one treatment arm was conducted to investigate changes
in health-related biomarkers (blood pressure and liver enzyme activity) and the
safety of 4 weeks of consuming a purple-fleshed sweet potato beverage in
Caucasian subjects. Twenty healthy adults, 18-70 years of age, with a body mass
index >25 kg/m(2), elevated blood pressure and elevated levels of liver function
biomarkers consumed two cartons of purple-fleshed sweet potato beverage (125 ml,
including 117 mg anthocyanin per carton) daily for 4 weeks. Hematology, serum
clinical profile, dipstick urinalysis and blood pressure were determined before
consumption, at 2 and 4 weeks of consumption and after a 2-week washout period. A
trend was found toward lowering systolic blood pressure during the treatment
period (p=0.0590). No significant changes were found in diastolic blood pressure
throughout the study period. Systolic blood pressure was significantly lower
after 4 weeks of consumption compared with before consumption (p=0.0125) and was
significantly higher after the 2-week washout period compared with after
consumption (p=0.0496). The serum alanine aminotransferase level significantly
increased over time, but aspartate aminotransferase and gamma-glutamyltransferase
levels stayed within the normal range of reference values. Safety parameters of
the blood and urine showed no clinically relevant changes. The consumption of a
purple-fleshed sweet potato beverage for 4 weeks resulted in no clinically
relevant changes in safety parameters of the blood and urine and showed a trend
toward lowering systolic blood pressure.
PMID- 27508115
TI - Protective effects of heat-killed Lactococcus lactis subsp. lactis BF3, isolated
from the intestine of chum salmon, in a murine model of DSS-induced inflammatory
bowel disease.
AB - Oxidative stress is considered an etiological factor responsible for several
symptoms of inflammatory bowel disease (IBD). In vitro anti-inflammatory
activities of heat-killed Lactococcus lactis subsp. lactis BF3 have been
reported. In this study, the anti-inflammatory effect of these cells was examined
using a dextran sodium sulphate (DSS)-induced murine IBD model. Administration of
heat-killed L. lactis BF3 via drinking water suppressed the IBD symptoms, such as
shortening of colon length, damage to the colon mucosa as observed under the
microscope, and spleen enlargement. This result suggests that heat-killed L.
lactis BF3 has the potential to treat IBD.
PMID- 27508116
TI - Effect of repeated oral administration of Bifidobacterium longum BB536 on
apomorphine-induced rearing behavior in mice.
AB - Schizophrenia is a chronic psychiatric illness. Disruption of the dopaminergic
system has been suggested to be the pathogenic cause of this disease. The effect
of Bifidobacterium longum BB536 (BB536) on schizophrenic behavior was
investigated in an animal model. Daily administration of BB536 (10(9) CFU/mouse,
p.o. for 2 weeks) was found to reduce rearing behavior augmented by the dopamine
receptor agonist apomorphine and to decrease the resting level of plasma
corticosterone and the ratio of kynurenine to tryptophan. These results suggest
the potential of BB536 for supplemental treatment of the symptoms of
schizophrenia.
PMID- 27508117
TI - Ectoparasitism on deep-sea fishes in the western North Atlantic: In situ
observations from ROV surveys.
AB - A complete understanding of how parasites influence marine ecosystem functioning
requires characterizing a broad range of parasite-host interactions while
determining the effects of parasitism in a variety of habitats. In deep-sea
fishes, the prevalence of parasitism remains poorly understood. Knowledge of
ectoparasitism, in particular, is limited because collection methods often cause
dislodgment of ectoparasites from their hosts. High-definition video collected
during 43 remotely operated vehicle surveys (2013-2014) provided the opportunity
to examine ectoparasitism on fishes across habitats (open slope, canyon,
seamount, cold seep) and depths (494-4689 m) off the northeastern U.S., while
providing high-resolution images and valuable observations of fish behavior. Only
9% (n = 125 individuals) of all observed fishes (25 species) were confirmed with
ectoparasites, but higher percentages (~33%) were observed for some of the most
abundant fish species (e.g., Antimora rostrata). Ectoparasites included two
copepod families (Lernaeopodidae, Sphyriidae) that infected four host species,
two isopod families (Cymothoidae, Aegidae) that infected three host species, and
one isopod family (Gnathiidae) that infected 19 host species. Hyperparasitism was
also observed. As host diversity declined with depth, ectoparasite diversity
declined; only gnathiids were observed at depths down to 3260 m. Thus, gnathiids
appear to be the most successful group to infect a diversity of fishes across a
broad depth range in the deep sea. For three dominant fishes (A. rostrata,
Nezumia bairdii, Synaphobranchus spp.), the abundance and intensity of
ectoparasitism peaked in different depths and habitats depending on the host
species examined. Notably, gnathiid infections were most intense on A. rostrata,
particularly in submarine canyons, suggesting that these habitats may increase
ectoparasite infections. Although ectoparasitism is often overlooked in deep-sea
benthic communities, our results demonstrate that it occurs widely across a
variety of habitats, depths, and locations and is a significant component of deep
sea biodiversity.
PMID- 27508118
TI - Haemosporidian parasite infections in grouse and ptarmigan: Prevalence and
genetic diversity of blood parasites in resident Alaskan birds.
AB - Projections related to future climate warming indicate the potential for an
increase in the distribution and prevalence of blood parasites in northern
regions. However, baseline data are lacking for resident avian host species in
Alaska. Grouse and ptarmigan occupy a diverse range of habitat types throughout
the northern hemisphere and are among the most well-known and important native
game birds in North America. Information regarding the prevalence and diversity
of haemosporidian parasites in tetraonid species is limited, with few recent
studies and an almost complete lack of genetic data. To better understand the
genetic diversity of haemosporidian parasites in Alaskan tetraonids and to
determine current patterns of geographic range and host specificity, we used
molecular methods to screen 459 tissue samples collected from grouse and
ptarmigan species across multiple regions of Alaska for infection by
Leucocytozoon, Haemoproteus, and Plasmodium blood parasites. Infections were
detected in 342 individuals, with overall apparent prevalence of 53% for
Leucocytozoon, 21% for Haemoproteus, and 9% for Plasmodium. Parasite prevalence
varied by region, with different patterns observed between species groups (grouse
versus ptarmigan). Leucocytozoon was more common in ptarmigan, whereas
Haemoproteus was more common in grouse. We detected Plasmodium infections in
grouse only. Analysis of haemosporidian mitochondrial DNA cytochrome b sequences
revealed 23 unique parasite haplotypes, several of which were identical to
lineages previously detected in other avian hosts. Phylogenetic analysis showed
close relationships between haplotypes from our study and those identified in
Alaskan waterfowl for Haemoproteus and Plasmodium parasites. In contrast,
Leucocytozoon lineages were structured strongly by host family. Our results
provide some of the first genetic data for haemosporidians in grouse and
ptarmigan species, and provide an initial baseline on the prevalence and
diversity of blood parasites in a group of northern host species.
PMID- 27508119
TI - Draft genome sequence of Staphylococcus aureus KT/312045, an ST1-MSSA PVL
positive isolated from pus sample in East Coast Malaysia.
AB - Most of the efforts in elucidating the molecular relatedness and epidemiology of
Staphylococcus aureus in Malaysia have been largely focused on methicillin
resistant S. aureus (MRSA). Therefore, here we report the draft genome sequence
of the methicillin-susceptible Staphylococcus aureus (MSSA) with sequence type 1
(ST1), spa type t127 with Panton-Valentine Leukocidin (pvl) pathogenic
determinant isolated from pus sample designated as KT/314250 strain. The size of
the draft genome is 2.86 Mbp with 32.7% of G + C content consisting 2673 coding
sequences. The draft genome sequence has been deposited in DDBJ/EMBL/GenBank
under the accession number AOCP00000000.
PMID- 27508120
TI - Characterization of the replication timing program of 6 human model cell lines.
AB - During the S-phase, the DNA replication process is finely orchestrated and
regulated by two programs: the spatial program that determines where replication
will start in the genome (Cadoret et al. (2008 Oct 14), Cayrou et al. (2011 Sep),
Picard et al. (2014 May 1) [1], [2], [3]), and the temporal program that
determines when during the S phase different parts of the genome are replicated
and when origins are activated. The temporal program is so well conserved for
each cell type from independent individuals [4] that it is possible to identify a
cell type from an unknown sample just by determining its replication timing
program. Moreover, replicative domains are strongly correlated with the partition
of the genome into topological domains (determined by the Hi-C method, Lieberman
Aiden et al. (2009 Oct 9), Pope et al. (2014 Nov 20) [5], [6]). On the one hand,
replicative areas are well defined and participate in shaping the spatial
organization of the genome for a given cell type. On the other hand, studies on
the timing program during cell differentiation showed a certain plasticity of
this program according to the stage of cell differentiation Hiratani et al. (2008
Oct 7, 2010 Feb) [7], [8]. Domains where a replication timing change was observed
went through a nuclear re-localization. Thus the temporal program of replication
can be considered as an epigenetic mark Hiratani and Gilbert (2009 Feb 16) [9].
We present the genomic data of replication timing in 6 human model cell lines:
U2OS (GSM2111308), RKO (GSM2111309), HEK 293T (GSM2111310), HeLa (GSM2111311),
MRC5-SV (GSM2111312) and K562 (GSM2111313). A short comparative analysis was
performed that allowed us to define regions common to the 6 cell lines. These
replication timing data can be taken into account when performing studies that
use these model cell lines.
PMID- 27508121
TI - Metagenomic analysis of fungal taxa inhabiting Mecca region, Saudi Arabia.
AB - The data presented contains the sequences of fungal Internal Transcribed Spacer
(ITS) and 18S rRNA gene from a metagenome of the Mecca region, Saudi Arabia.
Sequences were amplified using fungal specific primers, which amplified the
amplicon aligned between the 18S and 28S rRNA genes. A total of 460 fungal
species belonging to 133 genera, 58 families, 33 orders, 13 classes and 4 phyla
were identified in four contrasting locations. The raw sequencing data used to
perform this analysis along with FASTQ file are located in the NCBI Sequence Read
Archive (SRA) under accession numbers: SRR3150823, SRR3144873, SRR3150825 and
SRR3150846.
PMID- 27508122
TI - The draft genome sequence of Mangrovibacter sp. strain MP23, an endophyte
isolated from the roots of Phragmites karka.
AB - Till date, only one draft genome has been reported within the genus
Mangrovibacter. Here, we report the second draft genome shotgun sequence of a
Mangrovibacter sp. strain MP23 that was isolated from the roots of Phargmites
karka (P. karka), an invasive weed growing in the Chilika Lagoon, Odisha, India.
Strain MP23 is a facultative anaerobic, nitrogen-fixing endophytic bacteria that
grows optimally at 37 degrees C, 7.0 pH, and 1% NaCl concentration. The draft
genome sequence of strain MP23 contains 4,947,475 bp with an estimated G + C
content of 49.9% and total 4392 protein coding genes. The genome sequence has
provided information on putative genes that code for proteins involved in
oxidative stress, uptake of nutrients, and nitrogen fixation that might offer
niche specific ecological fitness and explain the invasive success of P. karka in
Chilika Lagoon. The draft genome sequence and annotation have been deposited at
DDBJ/EMBL/GenBank under the accession number LYRP00000000.
PMID- 27508123
TI - Context based computational analysis and characterization of ARS consensus
sequences (ACS) of Saccharomyces cerevisiae genome.
AB - Genome-wide experimental studies in Saccharomyces cerevisiae reveal that
autonomous replicating sequence (ARS) requires an essential consensus sequence
(ACS) for replication activity. Computational studies identified thousands of ACS
like patterns in the genome. However, only a few hundreds of these sites act as
replicating sites and the rest are considered as dormant or evolving sites. In a
bid to understand the sequence makeup of replication sites, a content and context
based analysis was performed on a set of replicating ACS sequences that binds to
origin-recognition complex (ORC) denoted as ORC-ACS and non-replicating ACS
sequences (nrACS), that are not bound by ORC. In this study, DNA properties such
as base composition, correlation, sequence dependent thermodynamic and DNA
structural profiles, and their positions have been considered for characterizing
ORC-ACS and nrACS. Analysis reveals that ORC-ACS depict marked differences in
nucleotide composition and context features in its vicinity compared to nrACS.
Interestingly, an A-rich motif was also discovered in ORC-ACS sequences within
its nucleosome-free region. Profound changes in the conformational features, such
as DNA helical twist, inclination angle and stacking energy between ORC-ACS and
nrACS were observed. Distribution of ACS motifs in the non-coding segments points
to the locations of ORC-ACS which are found far away from the adjacent gene start
position compared to nrACS thereby enabling an accessible environment for ORC
proteins. Our attempt is novel in considering the contextual view of ACS and its
flanking region along with nucleosome positioning in the S. cerevisiae genome and
may be useful for any computational prediction scheme.
PMID- 27508124
TI - Endoscopic Excision of Non-embolized Juvenile Nasopharyngeal Angiofibroma: Our
Technique.
AB - To approach Juvenile nasopharyngeal angiofibroma extending to the sphenoid sinus,
pterygoid wedge and minimal involvement of the pterygopalatine fossa (Radkowski
Stage 2 A) with an endoscopic technique without embolization with no recurrence
and minimal morbidity and mortality. This is a retrospective, descriptive study
based on the medical records of 15 patients with histologically confirmed JNA who
underwent endoscopic binostril four handed endoscopic excision in our centre
without embolisation between 2010 and 2015. All 15 patients were young males with
a mean age of 14.13 years who underwent endoscopic excision of JNA without
embolisation. Nasal obstruction (100 %) and epistaxis (100 %) were the most
common symptoms. Average surgery length was 1 h 41 min. Mean blood loss was 67.2
ml and none of patients required blood transfusion. All patients had crusting and
septal defect postoperatively, only 3 (20 %) had synechiae. Mean hospitalization
time was 3.66 days. 2 (13.33 %) of our patients had a residual tumor and one
(6.66 %) had a relapse in pterygoid wedge. There were no cases of death or
significant morbidity. The follow up period was 1 year. Endoscopic endo nasal bi
nostril four handed technique can achieve complete resection without embolization
in case of small to medium sized JNA s in the hands of an experienced surgeon
with minimal blood loss, low rates of recurrence and morbidity.
PMID- 27508125
TI - Presentations and Challenges in Tuberculosis of Head and Neck Region.
AB - (1) To study the different patterns of presentations of tuberculosis in Head and
Neck region. (2) To know the importance and reliability of ESR and Mantoux test
as an aid in diagnosis of tuberculosis. This study was conducted at Department of
ENT and Head and Neck Surgery, Gandhi Medical College, Bhopal, Madhya Pradesh
from January 2014 to June 2015. Patients presenting with lesions in the Head and
Neck region suspected of tuberculosis were subjected for cytological and
histological investigations. Those cases confirmed to be tuberculosis on the
basis of either of these tests were included in the study. Study comprised of 113
proven cases of tuberculosis of Head and Neck region. A female preponderance of
1:1.97 (M:F) ratio was noted. Most commonly involved structure was cervical lymph
node (92.92 %) followed by larynx, skin and oral mucosa (1.76 %). It was also
noted that Mantoux test was positive in 93.8 % of patients and ESR was >30 mm
(first hour) in 95.5 % of patients with tuberculosis. Most common presentation of
Tuberculosis in Head and Neck area was cervical lymphadenopathy. In a developing
country like India the population is mostly in the lower socioeconomic strata.
Access to various modern investigations is limited and diagnosis is challenging.
Here ESR and Mantoux test are helpful in purusing the case for further
evaluation. Based on these pointers cytologically negative cases can be taken up
for biopsy.
PMID- 27508126
TI - Comparative Study of Improvement of Nasal Symptoms Following Septoplasty with
Partial Inferior Turbinectomy Versus Septoplasty Alone in Adults by NOSE Scale: A
Prospective Study.
AB - To compare the symptomatic improvement of nasal symptoms following septoplasty
with partial inferior turbinectomy (groups A) versus septoplasty alone (groups B)
and to assess the improvement of nasal symptoms in both surgical groups before
and after surgery by NOSE scale. This Tertiary Hospital based study was carried
out between August 2012 and April 2014. 60 cases with septal deviation and
contralateral inferior turbinate hypertrophy. Nasal Obstruction Symptom
Evaluation (NOSE) scale for evaluating nasal symptoms. Patients were
alternatively divided into two surgical groups, group A. Septoplasty with partial
inferior turbinectomy and group B septoplasty alone. Post-operative patient's
symptoms evaluated by NOSE scale at 1, 3 and 6 months. Data analysed using
tables, graph and percentage and test of significance like paired t test,
Friedman test, Chi square test used. Post operative improvement following both
group A septoplasty with partial inferior turbinectomy and group B in those
undergoing septoplasty alone was highly significant (p < 0.001) at post-op 1, 3
and 6 months subjectively. When both groups were compared those undergoing
partial inferior turbinectomy surgery with septoplasty had highly significant
results (p < 0.001) for subjective assessment by NOSE scale. This study showed
that hypertrophied turbinate need to be addressed in chronic cases of nasal
obstruction with deviated nasal septum and contralateral turbinate hypertrophy.
partial inferior turbinectomy should be done in addition to septoplasty, its
highly effective modality for the treatment of nasal obstruction in patients with
deviated nasal septum. NOSE score can be used as a subjective tool for
symptomatic measurement of patients with nasal obstruction.
PMID- 27508127
TI - An Innovative Operative Method for Correction of Tracheal Stenosis.
AB - This is a case of failed attempt of hanging, resulted into cervical injury &
injury to the trachea. Patient was put on the ventilator for respiratory support
for long period. Poor recovery of the patient resulted into prolong tracheostomy
tube. Combine effect of all resulted into suprastomal tracheal stenosis. Due to
complexity of the problem a novel method was customized to correct the tracheal
stenosis. Strap muscle (Sternohyoid & Sternothyroid) was raised as a flap; free
cartilage was sandwiched in between and sutured to the created tracheal defect.
Bovine collagen was placed over a stent and placed in the tracheal lumen. Good
result was achieved post operatively in the form of adequate lumen, rigid
anterior wall during respiration, good mucosal lining without fibrosis and normal
speech.
PMID- 27508128
TI - Effect of Septoplasty on Cepstral Analysis of Voice.
AB - Resonance change is a common clinical symptom in individuals with deviated nasal
septum. Often this anatomical deficit is surgically treated by septoplasty.
Therefore monitoring resonance changes using acoustical tools is vital. Hence,
the study investigated cepstral measure differences in subjects with deviated
nasal septum compared to normals. A case-control study design involving 20
subjects within 18-40 years divided into Group I of 10 subjects with deviated
nasal septum (DNS) and Group II of 10 normal subjects participated. All the
subjects sustained nasalized vowel /a/ at 10 cm mouth-microphone distance for
minimum of 5 seconds. For Group I, voice sample was recorded in 2 conditions, 2
days pre-septoplasty and 1 month post-septoplasty. Cepstral peak prominence (CPP)
and smooth cepstral peak prominence (CPPS) values was extracted using the
Hillenbrand algorithm. Mean values revealed increased CPP and CPPS measure post
septoplasty when compared to pre-septoplasty. ANOVA showed statistically
significant difference only for CPPS at p = 0.00. The higher cepstral values of
post-septoplasty is due to widened nasal passage that leads to increased nasal
volume, decreased acoustic damping and increased nasal patency. These changes in
supraglottic chambers will result in a better acoustic space for good resonance.
However, the CPPS values were not similar to normal subjects because of scarring
or incomplete recovery of the outer mucosal layer of the nasal tract. Thus, we
can conclude that cepstral analysis is a sensitive tool to detect resonance
changes in the nasal patency.
PMID- 27508129
TI - Challenges in the Management of Laryngeal Stenosis.
AB - Laryngeal stenosis is one of the most complex and challenging problems in the
field of head and neck surgery. The management involves a multidisciplinary
approach with multiple complex procedures. In this study we discuss our
experience of laryngeal stenosis with regards to patient characteristics, cause
and management. A retrospective analysis of 35 patients of laryngeal stenosis
treated at a tertiary care centre was evaluated. Inclusion criteria were all
patients with laryngeal stenosis who required surgical intervention. Exclusion
criteria were patients with associated tracheal stenosis and laryngeal stenosis
due to cancer. Demographic data was recorded and findings relating to aetiology,
characteristics of stenosis and the various aspects of therapeutic procedures
performed are discussed with review of literature. Among 35 patients, 24 were
males and 11 females of the age group 2-79 years. 2 (5.7 %) patients had
supraglottic stenosis, 11 (31.4 %) had glottis stenosis, 16 (45.7 %) had
subglottic stenosis and 6 (17.1 %) had combined multiple sites stenosis. Each
patient underwent an average of 3.22 surgical procedures like microlaryngoscopy
and excision with cold instrument, CO2 laser excision or open procedures like
laryngofissure and excision and laryngoplasty. Montgomery t tube insertion was a
common procedure in 17 patients (48.6 %). Of the total 35 patients with severe
LS, 27 (77.1 %) patients were successfully decanulated. The results of glottic
(100 %) and supraglottic stenosis (100 %) are excellent as compared to subglottic
(68.8 %) and combined stenosis (50 %) of multiple sites. Laryngeal stenosis with
airway compromise causes significant morbidity to the patients and is a difficult
condition to treat in both adult and pediatric population. The need for multiple
surgical procedures is common in the treatment of laryngeal stenosis with the t
tube being an important aid in the management of this condition. Trauma
especially post intubation trauma is the commonest cause of laryngeal stenosis
and the involvement of subglottis has poor outcome as compared to other subsites.
PMID- 27508130
TI - Functional Endoscopic Sinus Surgery Versus Balloon Sinuplasty with Ethmoidectomy:
A 2-year Analysis in Pediatric Chronic Rhinosinusitis.
AB - To evaluate the 2-year post-operative outcomes of pediatric patients with chronic
rhinosinusitis (CRS) treated with balloon catheter sinuplasty (BCS) and
ethmoidectomy compared to functional endoscopic sinus surgery (FESS). Two-group,
retrospective cohort study of 28 children with CRS was performed. Of these 28
participants, 15 were treated with traditional FESS (53.6 %) and 13 (46.4 %)
underwent traditional ethmoidectomy with balloon sinuplasty. Pre-operative and 2
year postoperative total symptom scores and medications were compared. To examine
the potential long-term differences in surgical outcomes and surgical procedure
on symptom outcome, one-tailed Chi square analyses were employed. The mean age of
the children examined was 9.3 (SD = SD = 4.1; range 3-18) and 61.9 % were male.
Pre-operative symptomatology, medication and Lund Mackay scores were evaluated
for both groups and no significant differences were identified. Overall, 73.3 %
of children that underwent traditional FESS and 76.9 % of those who had BCS with
ethmoidectomy reported significant long-term improvement in at least one of their
pre-operative sinus complaints. Our data suggests that both BCS with
ethmoidectomy and traditional FESS are effective treatment options for
uncomplicated CRS and result in long-term alleviation of core sinus complaints,
as well as decreased sinus related medication use. Larger prospective studies are
needed to further evaluate these procedures.
PMID- 27508131
TI - Middle and Lower Face Soft Tissue Reconstruction: A 10-Year Retrospective Study.
AB - Retrospectively analyze the reconstruction methods and surgical outcomes of
patients with middle and lower face soft tissue defects treated at our hospital
over the past 10 years. 200 patients with middle and lower face soft tissue
defects were surgically reconstructed at our hospital. Medical charts were
retrospectively reviewed and analyzed to abstract the pertinent information. The
lesion was mainly at the eyelid, lips, chin and nasal-cheek region. There were 41
(63.08 %) men and 24 (36.92 %) women. In our study, male to female ratio = 1.7:1.
We used direct closure for night patients, local flap for 141 patients, free flap
for 38 patients, combined flap for 12 patients involving extensive mid face and
lower face defects. Most patients had their tumor resected and reconstructed in
single stage procedure mostly with local advancement flap, and no flap failure
was presented post-operatively. Middle and lower face soft tissue defects can be
successfully treated with local flap in a single stage approach and step-by-step
approach.
PMID- 27508132
TI - Questionable Necessity for Removing Submandibular Gland in Neck Dissection in
Squamous Cell Carcinoma of Oral Cavity.
AB - To assess whether submandibular gland is involved by metastasis in cases of oral
cavity squamous cell carcinomas. It was a retrospective study, where we reviewed
the records of the patients who underwent neck dissections for Squamous Cell
Carcinoma of the oral cavity. It included 112 patients who had undergone 115 neck
dissections (three patients had undergone bilateral neck dissection), either
therapeutic or prophylactic. No pathologic evidence of metastasis to
submandibular gland was seen in any of the case. Preservation of submandibular
glands can be a good technique for reducing future complications in a patient
undergoing Neck Dissection wherever feasible. Therefore, if there is no need to
expose large oral cavity tumors through the submandibular triangle, or when there
is no direct extension of the primary and/or regional lymph nodes into the
submandibular gland, it may be safe to preserve the submandibular gland.
PMID- 27508133
TI - Challenges During Baha Surgery: Our Experience.
AB - Baha has proven performance and advantages for patients with aural atresia or
chronic ear drainage. Being a per cutaneous osseo integrated implant the skin
around the fixture is in contact with a foreign body that leads to chronic
inflammatory reaction and complications such as skin irritation and overgrowth
occur frequently. Challenges that are faced during Baha surgery include those
during candidate selection, work up, anesthesia related as well as intra
operative and post operative complications. Ours was a retrospective and
observational study where case records of 10 patients who underwent Baha surgery
in the Department of E.N.T during the time period from January 2010 to June 2013
were reviewed. Here, the candidates were advised Baha either for congenital
external ear deformity or single sided deafness. Out of 10 patients, who
underwent Baha implantation, 8 underwent single staged Baha implant and two
patients had two staged implant owing to bone thickness <3 mm behind temporo
parietal suture line on HRCT Temporal bone. The complications observed were skin
infection (Holgers grade 2) around the site of implant in two patients, skin
overgrowth due to more thickness of scalp (Holgers grade 4) in one of the
patient. The patient had to undergo revision surgery to replace the abutment. And
one of the patients underwent failure of osseointegration and was re-implanted
later. Proper surgical technique and post operative wound care play an important
role in avoiding complications.
PMID- 27508135
TI - Comparative Study of Apo-Cetirizine Single Therapy and Intermittent Sequential
Therapy with Cetirizine, Loratadine and Chlorpheniramine in Allergic Rhinitis.
AB - There are limited numbers of articles, studying combined use of antihistamines.
In this study, we compare single therapy of Apo-Cetirizine with a new regimen of
intermittent sequential therapy with cetirizine, loratadine and chlorpheniramine
in treatment of seasonal allergic rhinitis. This randomized clinical trial was
performed between April and September at the peak prevalence of seasonal allergic
rhinitis. Fifty-four eligible patients diagnosed clinically to have seasonal
allergic rhinitis were randomized in two groups: 24 cases in single therapy arm,
received Apo-Cetirizine 10 mg tablet daily and in other arm, 30 patients received
sequential regimen of cetirizine 10 mg tablet, loratadine 10 mg tablet and
chlorpheniramine 4 mg tablet, one tablet each day. Major Symptom Complex Score
(MSCS) and Total Symptom Complex Score (TSCS) of patients were recorded before
treatment and after 30 days of treatment in two groups. The average post
treatment MSCS and TSCS in combination therapy group showed better improvement
than single therapy group but difference was not statistically significant (p
value = 0.053 and p value = 0.104 respectively). Combination therapy regimen was
better in improvement of nasal congestion (p value = 0.006). There were no
significant difference between two groups in efficacy, side effects and patient's
satisfaction. Combination therapy would be effective on a wide spectrum of
symptoms with lower price and theoretically offers lower chance of tolerance and
re-appearance of complaints.
PMID- 27508134
TI - Uses of Various Grafting Techniques in External Approach Rhinoplasty: An
Overview.
AB - The surgeons performing rhinoplasty found Graft selection the greatest challenge.
To avoid an immune response the preferred choice thus far for nasal
reconstruction would be autograft compared to allograft due to its lower rate of
rejection. We have evaluated 30 patients who underwent open rhinoplasty and We
used conchal and septal cartilaginous grafts in various forms by the open
approach to correct various nasal deformities compared our experience regarding
the operative technique, graft availability, indications, and limitations. No
bony graft material or synthetic materials were used. Preoperative extensive
evaluation of the patient was done in order to determine the type of deformity
and the type of graft to be used in order to correct the deformity. Preoperative
and postoperative photographs were taken in four basic views: frontal, lateral,
lateral-oblique and basal in order to assess the results of the surgery. The
study was done on 30 patients (20 male and 10 females) using the external
rhinoplasty approach using the septal and conchal cartilages in different forms.
Autologous septal cartilage was used in most of the patients (25 out of 30) and
conchal cartilage was used in 5 patients. Multiple grafting techniques were used
in some patients. Three patients had traumatic etiology. Columellar strut graft
along with TIG technique was used in 16 patients, spreader graft was used in 8
patients, and septal extension graft was used in 5 patient and shield graft in 1
patient. Septorhinoplasty continues to evolve through various new techniques and
modifications with the main goal to improve functional nasal airway and to
restore cosmetic harmony to the face. Optimum result is very much dependent on
the surgeon's attention to functional, aesthetic, and reconstructive principles
and graft selection.
PMID- 27508136
TI - Brainstem Evoked Response Audiometry (BERA) in Neonates with Hyperbillirubinemia.
AB - (1) To study the BERA changes in neonates with unconjugated hyperbilirubinemia.
(2) To compare the BERA changes in the neonates with unconjugated
hyperbilirubinemia before and after therapy. Thirty consecutive term appropriate
for gestational age (AGA) neonates presenting to NICU with total serum bilirubin
requiring intervention (using the American Academy of Pediatrics guidelines) were
included in the study as cases and thirty normal term AGA neonates with
uneventful peri-natal period and a maximum measured serum bilirubin <12 mg/dl in
case of term baby were included as controls after obtaining informed consent.
Initial BERA was done within 3-24 h of hospitalization after obtaining informed
consent from parents, at the time of discharge and at 3 month followup. Machine
used for recording BERA was intelligent hearing system version 3.3. In our study
out of the 30 cases 10 (33.3 %) cases were found to have BERA changes in the form
of absent wave forms, raised threshold, prolonged latencies or prolonged inter
peak latencies. In our study, it was observed that there was statistically
significant correlation (p value < 0.005) between increasing bilirubin level and
BERA changes. Correlation of the findings of this study with previous few studies
indicates that BERA can be used as a useful non invasive tool to determine
auditory functions in the neonate especially changes of early bilirubin toxicity.
PMID- 27508137
TI - Boomerang-Shaped Chondro-Perichondral Graft Versus Temporalis Muscle Fascia
Graft: Which One is to be Trusted?
AB - The aim of this study was to compare anatomical and audiological results of
boomerang-shaped chondroperichondrial graft (BSCPG) with temporal muscle fascia
in type 1 tympanoplasties. Sixty-eight patients in BSCPG group and 54 patients in
fascia group were evaluated. Otomicroscopic examination was done periodically
till 24 months as for graft perforation, lateralization and retraction and mean
air conduction threshold and airbone gap values were measured. At long term
controls, in BSCPG group, rates of neomembrane, perforation, retraction and
lateralization were 91.17 % (n = 62), 8.82 % (n = 6), 4.41 % (n = 3) and 0 % (n =
0), respectively. In fascia group, the corresponding rates were 79.62 % (n = 43),
20.37 % (n = 11), 12.96 % (n = 7) and 3.7 % (n = 2), respectively. In both
groups, mean postoperative PTA and ABG values were significantly better while
postoperative same values were significantly different between groups (p = 0.044
and 0.032, respectively). Compared to fascia, BSCPG is an ideal grafting
technique in the repair of tympanic membrane perforations.
PMID- 27508138
TI - Cervical Node Tuberculosis in Adults of an Urban Middle Class Community:
Incidence and Management.
AB - The aim of this study is to estimate the incidence of cervical node tuberculosis
(TB) in an urban middle class population and to describe an effective protocol
for management of cervical lymphadenopathy. The present study is a prospective
observational study conducted over two years (2007-2009) in a community hospital
in Mumbai, India. All adults (age >=14 years) presenting with cervical
lymphadenopathy, not resolving were included and their details of history and
examination were noted. All patients were subjected to fine needle aspiration
cytology (FNAC) and biopsy was done selectively as indicated. The response at 1,
3 and 6 months of starting anti tuberculous treatment (ATT) were noted. A total
of 191 patients were included in this study. The mean age was 41 years and male
to female ratio was 1:1.1 in patients with cervical lymphadenopathy. A history of
contact with a patient of TB was the most significantly associated history seen
in patients diagnosed to have TB of cervical nodes (p < 0.001). TB (38.7%)
followed by reactive nodes (37.6%) were the most common etiologies. A 90.6%
response rate was seen in patients taking 6 months ATT for cervical node TB. The
incidence of adult (>=14 years) cervical node TB was 52/100,000 people in an
urban middle class community in Mumbai. A single swelling in the neck without
other associated symptoms or signs was the commonest mode of presentation of TB
of the neck nodes. A history of contact with TB, demonstrated an association with
the final diagnosis of tuberculous lymphadenopathy.
PMID- 27508139
TI - Sinonasal Anatomical Variants: CT and Endoscopy Study and Its Correlation with
Extent of Disease.
AB - To evaluate the incidence of anatomical variations in sinonasal area by nasal
endoscopy and CT scan paranasal sinuses and to correlate the anatomical
variations in sinonasal area with extent of disease. The present study was
conducted on 40 patients of chronic sinusitis. All the patients underwent CT scan
paranasal sinus axial and coronal view and nasal endoscopy. The most common
anatomical variations were agger nasi cells (80 %), deviated nasal septum (72.5
%) and concha bullosa (47.5 %). Other anatomical variations seen in sinonasal
region were uncinate process variations, paradoxical middle turbinate, haller
cells, accessory ostia of maxillary sinus, multiseptated sphenoid. Osteomeatal
unit (87.5 %) and maxillary sinuses (87.5 %) were the most commonly involved
which was followed by anterior ethmoids (70 %), posterior ethmoids (50 %),
frontal sinuses (32.5 %) and the sphenoids (20 %). Considering the results
obtained, we believe that anatomical variations may increase the risk of sinus
mucosal disease. We therefore, emphasize the importance of a careful evaluation
of CT study in patients with persistent symptoms of chronic rhinosinusitis.
PMID- 27508140
TI - Clinical Predictors of Streptomycin-Vestibulotoxicity.
AB - The Global tuberculosis control is challenged with a growing resistance to
antitubercular treatment (ATT) culminating in resistant (MDR/XDR) strains; an
important factor being premature withdrawal of streptomycin owing to its
morbidity particularly nephrotoxicity and cochleotoxicity as guidelines for their
prevention exist. An attempt is made here to address the least recognized and
most debilitating vestibular toxic effects of streptomycin and defining a
vestibular-protocol for its early detection and progression. Thirty two
prospective patients (treatment-failures, relapse and default cases) undergoing
ATT (24 shots of IM streptomycin 15-20 mg/kg over 8 weeks) underwent complete
vestibular workup including vestibulo-ocular and vestibulo-spinal reflex
assessment with an attempt to closely follow them. Four categories (I: No-, II:
Occult-, III: Delayed-Manifest- and IV: Manifest-vestibulotoxicity) were defined.
The DHI and casual gait abnormality clearly differentiated III/IV from I/II. The
occilopsia and head thrust tests significantly differentiated II from I. Rotation
and bithermal calorics significantly differentiated I from II and II from III/IV.
The Fukuda, Rhomberg, Tandem-Rhomberg and CTSIB were significant in
differentiating I from II and II from III/IV. Dix-Hallpike and Positional tests
were of no significance in the entire study. The Occilopsia and Head-Thrust tests
that showed 100 % positivity for II to IV are more likely to better predict
'manifest' or 'occult' -vestibulotoxicity while DHI and casual gait assessment
may be carried out by a paramedic at a peripheral center to suspect
vestibulotoxicity. Since we found absolute compliance with our series we feel
that vestibulotoxicity may not be a deciding factor for termination of
streptomycin provided an in-built mechanism for patient support/counseling be
incorporated in management schedule.
PMID- 27508141
TI - An Intriguing Case of Ectasia of External Jugular Vein Presenting as Intermittent
Neck Mass.
AB - Ectasia of external jugular vein is a rare entity presenting as an intermittent
neck swelling. High index of suspicion is required to diagnose the condition.
Ultrasonography with Doppler before, during and after valsalva manoeuvre is the
preferred method for diagnosis. The treatment is conservative for asymptomatic
patients and surgery is reserved for patients with complications.
PMID- 27508142
TI - Adenoid Cystic Carcinoma of Buccal Mucosa: A Rare Case Report.
AB - Adenoid cystic carcinoma is a malignant neoplasm most commonly originating in
salivary glands of head and neck region. Among intra oral adenoid cystic
carcinoma, buccal mucosa is among the rarest sites. We report a case of adenoid
cystic of buccal mucosa in a 40-year old female. We have discussed the clinical
features, histopathology, diagnosis and treatment along with a brief review of
the relevant literature. Although the buccal mucosa is an uncommon site for
adenoid cystic carcinoma, the relatively indolent growth pattern of this case and
its location which is rather atypical for this type of salivary gland malignancy
primarily warrants the necessity behind reporting of this case. Secondly, adenoid
cystic carcinoma should be considered in the differential diagnosis of mass of
buccal mucosa. It is important to identify such cases rather early and surgical
removal with adequate margins is the treatment of choice .
PMID- 27508143
TI - Metastatic Renal Cell Carcinoma Presenting as Nasal Mass: Case Report and Review
of Literature.
AB - Sinonasal neoplasms are rare and exceptional site for metastatic tumours and
comprising <3 % of all malignant aerodigestive tumours and <1 % of all
malignancies. Renal cell carcinoma is known to metastasise to the most unusual
sites, the sinonasal region being one of them. We here by present a case of 60
year old male patient who presented with epistaxis and nasal obstruction.
Clinical examination and CT scan revealed a tumour in the right nasal cavity and
maxillary sinus. The presence of primary renal cell carcinoma was recognized only
after surgical removal of metastatic tumour. Very few reports have been presented
in literature of metastatic renal cell carcinoma in the sinonasal region. We
present this case to document its occurrence; highlight the rarity, presentation
and difficulties in diagnosis and treatment along with review of literature.
PMID- 27508144
TI - Leiomyoma of External Auditory Canal.
AB - This article reports a case of piloleiomyoma of external auditory canal, which is
the 7th case of leiomyoma of the external auditory canal being reported and the
2nd case of leiomyoma arising from arrectores pilorum muscles, all the other five
cases were angioleiomyomas, arising from blood vessels. A 52 years old male
presented with a mass in the right external auditory canal and decreased hearing
of 6 months duration. Tumor excision done by end aural approach.
Histopathological examination report was leiomyoma. It is extremely rare for
leiomyoma to occur in the external auditory canal because of the non-availability
of smooth muscles in the external canal. So it should be considered as a very
rare differential diagnosis for any tumor or polyp in the ear canal.
PMID- 27508145
TI - Unusual Presentation of Chordoma in Nose.
AB - Chordomas are uncommon tumors of the bone representing 1-4 % of all primary bone
tumors. These typically involve axial skeleton. Primary nasal presentation of
chordoma is a rare occurrence and is usually misdiagnosed till the
histopathological confirmation. We present a case of chordoma in nasal cavity
treated by wide local resection and also present a review of literature
discussing various facets in its presentation and management.
PMID- 27508146
TI - Giant Sclerosing Oral Rhabdomyosarcoma-A Unique Case.
AB - We present a case of oral Rhabdomyosarcoma in a 50 years old man presenting with
a huge mass in the oral cavity. Pre operative investigations showed the mass to
be Rhabdomyosarcoma. The mass was excised and subjected to histopathogical and
immunohistochemical examinations which confirmed to be Rhabdomyosarcoma.
PMID- 27508147
TI - Ultrasonography Guided Excision of Isolated Cysticercosis of the Temporalis
Muscle Causing Intractable Headache: A Rare Case Report.
AB - Cysticercosis cellulosae is a systemic parasitic infection caused by the larval
stage of pork tapeworm, Taenia solium which involve humans as either a definitive
or secondary hosts. The central nervous system is the most important primary site
of involvement. Cases of cysticercosis presenting as an isolated muscle mass is
an extremely rare entity and demands documentation. We report an extremely
unusual case of isolated cysticercosis of the temporalis muscle causing
intractable headache which presented a diagnostic challenge. The condition was
surgically treated by ultrasonography guided excision of the cysticercosis
swelling in the temporalis muscle. We also emphasize on the role of proper
imaging modalities in the diagnosis and treatment of such unique cases.
PMID- 27508148
TI - Interaction of ACTN3 gene polymorphism and muscle imbalance effects on kinematic
efficiency in combat sports athletes.
AB - PURPOSE: The purpose of this study was to determine the interaction of ACTN3 gene
polymorphism and muscle imbalance effects on kinematic efficiency changes in
combat sports athletes. METHODS: Six types of combat sports athletes (Judo,
Taekwondo, boxing, kendo, wrestling, and Korean Ssi-reum) participated in the
study. ATCN3 gene polymorphism and muscle imbalance in lower extremity were
evaluated followed by analysis of differences of moment in hip, knee, and ankle
joint during V-cut jumping and stop. To examine the moment difference due to an
interaction of ATCN3 polymorphism and muscle imbalance, all participants were
divided into 4 groups (R+MB, R+MIB, X+MB, and X+MIB). RESULTS: There was no
significant difference of hip, knee, and ankle joint moment in R allele and X
allele during V-cut jumping and stop based on ACTN3 gene polymorphism. Otherwise,
muscle imbalance of knee moment in X-axis and ground reaction force of knee in Z
axis showed a higher significance in muscle imbalance during V-cut jumping and
stop compared to muscle balance (p<0.05). In addition, joint analysis showed that
muscle imbalance in X allele group had significantly higher knee moment of V-cut
ground reaction force in X-axis and higher ankle moment of jumping ground
reaction force in X and Z-axis compared to muscle balance with R and/or X group
(p <0.05). CONCLUSION: This study confirmed that muscle imbalance in lower
extremity of combat athletes might induce higher risk factors of sports injury
incidence than genetic factor and training might reduce the ratio of sports
injury risk incidence.
PMID- 27508149
TI - The effects of senior brain health exercise program on basic physical fitness,
cognitive function and BDNF of elderly women - a feasibility study.
AB - PURPOSE: This study was to investigate the impacts of senior brain heath exercise
(SBHE) program for 12 weeks to basic active physical fitness, cognitive function
and brain derived neurotrophic factor (BDNF) in elderly women. METHODS: Subject
of this study is total of 24 women in the age of 65-79 who can conduct normal
daily activity and communication but have not participated in regular exercise in
recent 6 months. The study groups were divided into an exercise group (EG, n=13)
and a control group (CG, n=11). The exercise program was consisted of SBHE, and
training frequency was 4 times weekly, of which training time was a total of 50
minutes each time in level of intensity of 9-14 by rating of perceived exertion
(RPE). RESULTS: First, 12-week SBHE program has shown statistical increase in
basic physical fitness in the EG comparing with the CG, such as lower body
strength, upper body strength and aerobic endurance, but not in flexibility,
agility and dynamic balance. Second, in the case of Mini-mental state examination
Korean version (MMSE-K) and BDNF, it showed that there was a statistically
significant increase in the EG comparing with the CG. CONCLUSION: In this study,
12-week SBHE program has resulted in positive effect on change of basic physical
fitness (strength and aerobic endurance), cognitive function and BDNF. If above
program adds movements that can enhance flexibility, dynamic balance and agility,
this can be practical exercise program to help seniors maintain overall healthy
lifestyle.
PMID- 27508150
TI - The effects of long-term whole-body vibration and aerobic exercise on body
composition and bone mineral density in obese middle-aged women.
AB - PURPOSE: The purpose of this study was to determine the effectiveness of whole
body passive vibration exercise and its differences from aerobic exercise on body
composition, bone mineral density (BMD) and bone mineral content (BMC). METHODS:
Obese middle-aged women (n=33 out of 45) with 34+/-3% body fat completed the
training protocol. They were randomly assigned into diet (n=9; control group),
diet plus whole-body vibration exercise (n=13; vibration group), and diet plus
aerobic exercise (n=11; aerobic group) groups and we compared their body
composition, BMD, and BMC before and after 9 months of training. There were no
significant differences in nutrient intake among groups during the training
period. RESULTS: Relative body fat (%) decreased significantly (p < .05) in all
three groups and the exercise groups showed a greater reduction in fat mass than
the diet only group. BMD in the whole body, lumbar spine, hip and forearm were
not significantly different among the three groups. Total body BMC increased
significantly in the vibration group throughout the first 6 months of training.
CONCLUSION: Results suggest that long- term vibration training when used in
conjunction with a diet program is as effective as aerobic exercise with a diet
program in improving body composition of obese middle-aged women without
compromising BMC or BMD. Thus, it can be considered a novel and effective method
for reducing body fat.
PMID- 27508151
TI - Exercise and dietary change ameliorate high fat diet induced obesity and insulin
resistance via mTOR signaling pathway.
AB - PURPOSE: The purpose of this study was to investigate the effect of exercise and
dietary change on obesity and insulin resistance and mTOR signaling protein
levels in skeletal muscles of obese rats. METHODS: Sixty male Sprague-Dawley rats
were divided into CO (Normal diet) and HF (High Fat diet) groups in order to
induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO +
Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND +
Training) groups (10 rats / group). The training groups underwent moderate
intensity treadmill exercise for 8 weeks, after which soleus muscles were excised
and analyzed. Data was statistically analyzed by independent t-test and One-way
ANOVA tests with a 0.05 significance level. RESULTS: Fasting blood glucose,
plasma insulin, and HOMA-IR in the HF group were significantly higher, as
compared with other groups (p <.05). Protein levels of insulin receptor subunit-1
(IRS-1), IRS-2, and p-Akt were significantly higher in the HFT, HFND, and HFNDT
groups, as compared with HF group. In addition, the protein levels of the
mammalian target of rapamycin complex 1 (mTORC1) and ribosomal S6 protein kinase
1 were significantly decreased by exercise and dietary change (p <.05). However,
mTORC2 and phosphoinositide 3-kinase were significantly increased (p <.05).
CONCLUSION: In summary, despite the negative impact of continuous high fat
intake, regular exercise and dietary change showed a positive effect on insulin
resistance and mTOR signaling protein levels.
PMID- 27508152
TI - Characterization of the metabolic effect of beta-alanine on markers of oxidative
metabolism and mitochondrial biogenesis in skeletal muscle.
AB - PURPOSE: beta-alanine is a common component of numerous sports supplements
purported to improve athletic performance through enhanced carnosine biosynthesis
and related intracellular buffering. To date, the effects of beta-alanine on
oxidative metabolism remain largely unexplored. This work investigated the
effects of beta-alanine on the expression of proteins which regulate cellular
energetics. METHODS: C2C12 myocytes were cultured and differentiated under
standard conditions followed by treatment with either beta-alanine or
isonitrogenous non-metabolizable control D-alanine at 800MUM for 24 hours.
Metabolic gene and protein expression were quantified by qRT-PCR and
immunoblotting, respectively. Glucose uptake and oxygen consumption were measured
via fluorescence using commercially available kits. RESULTS: beta-alanine-treated
myotubes displayed significantly elevated markers of improved oxidative
metabolism including elevated peroxisome proliferator-activated receptor
beta/delta (PPARbeta/delta) and mitochondrial transcription factor a (TFAM) which
led to increased mitochondrial content (evidenced by concurrent increases in
cytochrome c content). Additionally, beta-alanine-treated cells exhibited
significantly increased oxygen consumption compared to control in a
PPARbeta/delta-dependent manner. beta-alanine significantly enhanced expression
of myocyte enhancer factor 2 (MEF-2) leading to increased glucose transporter 4
(GLUT4) content. CONCLUSION: beta-alanine appears to increase cellular oxygen
consumption as well as the expression of several cellular proteins associated
with improved oxidative metabolism, suggesting beta-alanine supplementation may
provide additional metabolic benefit (although these observations require in vivo
experimental verification).
PMID- 27508153
TI - The effect of exercise training combined with PPARgamma agonist on skeletal
muscle glucose uptake and insulin sensitivity in induced diabetic obese Zucker
rats.
AB - PURPOSE: Exercise training with PPARgamma agonist is expected to increase glucose
uptake and improve insulin sensitivity in skeletal muscle of patients with
diabetes. However, its mechanisms to effect glucose uptake and insulin
sensitivity in skeletal muscle are unclear. METHODS: The mechanism of action was
determined by co-treatment with PPARgamma agonist- rosiglitazone and exercise
training in streptozotocin induced-diabetic obese Zucker rats. Exercise training
was carried out for 6 weeks (swimming, 1 h/day, 5 times/week, 5% weight/g, 32+/
1C) with rosiglitazone treatment (3mg/kg/day, 6weeks). RESULTS: Glucose uptake
and insulin sensitivity was decreased in diabetic than normal animals. Exercise
training and rosiglitazone treatment respectively increased the expression of
PPAR(peroxisome proliferators-activated receptor)-alpha, -beta/delta, -gamma, PGC
1alpha(PPAR-gamma coactivator-1alpha), adiponectin, GLUT-4(glucose transportor-4)
and p-AMPK-alpha2(phospho-AMP activated protein kinase-alpha2) in EDL and SOL of
diabetic, as compared to normal animals. Interestingly, training combined with
rosiglitazone significantly increased glucose uptake and insulin sensitivity,
which resulted in high expression of all molecules in diabetic than all other
groups. CONCLUSION: These results indicated that exercise training combined with
rosiglitazone might mediate regulation of glucose uptake and insulin sensitivity
in skeletal muscle. Therefore, exercise training combined with rosiglitazone may
be recommended as complementary therapies for diabetes.
PMID- 27508154
TI - GLUT2 proteins and PPARgamma transcripts levels are increased in liver of
ovariectomized rats: reversal effects of resistance training.
AB - PURPOSE: This study investigated the effects of ovariectomy (Ovx) and 12 weeks of
resistance training (RT) on gene expression of GLUT2, the main glucose
transporter in the liver, and on PPARgamma, a transcription factor known to
target GLUT2 expression. METHODS: Forty Holtzman rats were divided into 5 groups:
Sham-sedentary (Sed), Sham- RT, Ovx-Sed, Ovx-RT, and Ovx-Sed with hormone
replacement (E2). The RT protocol consisted of sessions held every 72 h for 12
weeks, during which the animals performed 4 to 9 vertical climbs (1.1 m) at 2 min
intervals with progressively heavier weights (30 g after the fourth climb) tied
to the tail. The E2 silastic capsule was inserted into the rats' backs 48 hours
before the first RT session. RESULTS: In addition to liver fat, GLUT2 protein
levels and PPARgamma transcripts were increased (P < 0.05) in Ovx compared to
Sham-Sed animals, suggesting increased hepatic glucose uptake under estrogen
deficient conditions. RT and E2 in Ovx rats decreased liver fat accumulation as
well as GLUT2 and PPARgamma gene expression to the level of Sham- Sed animals.
CONCLUSION: The results of this study suggest that liver GLUT2 as well as
PPARgamma expression in Ovx rats are accompanied by increased fat accumulation
and glucose uptake, thus providing a substrate for increased de novo lipogenesis.
RT appears to be an appropriate exercise model to circumvent these effects.
PMID- 27508156
TI - Criteria for clinical translucency evaluation of direct esthetic restorative
materials.
AB - The purpose of this review was to suggest practical criteria for the clinical
translucency evaluation of direct esthetic restorative materials, and to review
the translucency with these criteria. For the evaluation of reported translucency
values, measuring instrument and method, specimen thickness, background color,
and illumination should be scrutinized. Translucency parameter (TP) of 15 to 19
could be regarded as the translucency of 1 mm thick human enamel. Visual
perceptibility threshold for translucency difference in contrast ratio (DeltaCR)
of 0.07 could be transformed into DeltaTP value of 2. Translucency differences
between direct and indirect resin composites were perceivable (DeltaTP > 2).
Universal and corresponding flowable resin composites did not show perceivable
translucency differences in most products. Translucency differed significantly by
the product within each shade group, and by the shade group within each product.
Translucency of human enamel and perceptibility threshold for translucency
difference may be used as criteria for the clinical evaluation of translucency of
esthetic restorative materials.
PMID- 27508155
TI - Altered potassium ATP channel signaling in mesenteric arteries of old high salt
fed rats.
AB - PURPOSE: Both aging and the consumption of a high salt diet are associated with
clear changes in the vascular system that can lead to the development of
cardiovascular disease; however the mechanisms are not clearly understood.
Therefore, we examined whether aging and the consumption of excess salt alters
the function of potassium ATP-dependent channel signaling in mesenteric arteries.
METHODS: Young (7 months) and old (29 months) Fischer 344 x Brown Norway rats
were fed a control or a high salt diet (8% NaCl) for 12 days and mesenteric
arteries were utilized for vascular reactivity measurements. RESULTS:
Acetylcholine-induced endothelium relaxation was significantly reduced in old
arteries (81 +/- 4%) when compared with young arteries (92 +/- 2%). Pretreatment
with the potassium-ATP channel blocker glibenclamide reduced relaxation to
acetylcholine in young arteries but did not alter dilation in old arteries. On a
high salt diet, endothelium dilation to acetylcholine was significantly reduced
in old salt arteries (60 +/- 3%) when compared with old control arteries (81 +/-
4%). Glibenclamide reduced acetylcholine-induced dilation in young salt arteries
but had no effect on old salt arteries. Dilation to cromakalim, a potassium-ATP
channel opener, was reduced in old salt arteries when compared with old control
arteries. CONCLUSION: These findings demonstrate that aging impairs endothelium
dependent relaxation in mesenteric arteries. Furthermore, a high salt diet alters
the function of potassium-ATP-dependent channel signaling in old isolated
mesenteric arteries and affects the mediation of relaxation stimuli.
PMID- 27508157
TI - Cytotoxicity and biocompatibility of Zirconia (Y-TZP) posts with various dental
cements.
AB - OBJECTIVES: Endodontically treated teeth with insufficient tooth structure are
often restored with esthetic restorations. This study evaluated the cytotoxicity
and biological effects of yttria partially stabilized zirconia (Y-TZP) blocks in
combination with several dental cements. MATERIALS AND METHODS: Pairs of zirconia
cylinders with medium alone or cemented with three types of dental cement
including RelyX U200 (3M ESPE), FujiCEM 2 (GC), and Panavia F 2.0 (Kuraray) were
incubated in medium for 14 days. The cytotoxicity of each supernatant was
determined using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) assays on L929 fibroblasts and MC3T3-E1 osteoblasts. The levels of
interleukin-6 (IL-6) mRNA were evaluated by reverse transcription polymerase
chain reaction (RT-PCR), and IL-6 protein was evaluated by enzyme-linked
immunosorbent assays (ELISA). The data were analyzed using one-way ANOVA and
Tukey post-hoc tests. A p < 0.05 was considered statistically significant.
RESULTS: The MTT assays showed that MC3T3-E1 osteoblasts were more susceptible to
dental cements than L929 fibroblasts. The resin based dental cements increased IL
6 expression in L929 cells, but reduced IL-6 expression in MC3T3-E1 cells.
CONCLUSIONS: Zirconia alone or blocks cemented with dental cement showed
acceptable biocompatibilities. The results showed resin-modified glass-ionomer
based cement less produced inflammatory cytokines than other self-adhesive resin
based cements. Furthermore, osteoblasts were more susceptible than fibroblasts to
the biological effects of dental cement.
PMID- 27508158
TI - Preference of undergraduate students after first experience on nickel-titanium
endodontic instruments.
AB - OBJECTIVES: This study aimed to compare two nickel-titanium systems (rotary vs.
reciprocating) for their acceptance by undergraduate students who experienced
nickel-titanium (NiTi) instruments for the first time. MATERIALS AND METHODS:
Eighty-one sophomore dental students were first taught on manual root canal
preparation with stainless-steel files. After that, they were instructed on the
use of ProTaper Universal system (PTU, Dentsply Maillefer), then the WaveOne (WO,
Dentsply Maillefer). They practiced with each system on 2 extracted molars,
before using those files to shape the buccal or mesial canals of additional first
molars. A questionnaire was completed after using each file system, seeking
students' perception about 'Ease of use', 'Flexibility', 'Cutting-efficiency',
'Screwing-effect', 'Feeling-safety', and 'Instrumentation-time' of the NiTi
files, relative to stainless-steel instrumentation, on a 5-point Likert-type
scale. They were also requested to indicate their preference between the two
systems. Data was compared between groups using t-test, and with Chi-square test
for correlation of each perception value with the preferred choice (p = 0.05).
RESULTS: Among the 81 students, 55 indicated their preferred file system as WO
and 22 as PTU. All scores were greater than 4 (better) for both systems, compared
with stainless-steel files, except for 'Screwing-effect' for PTU. The scores for
WO in the categories of 'Flexibility', 'Screwing-effect', and 'Feeling-safety'
were significantly higher scores than those of PTU. A significant association
between the 'Screwing-effect' and students' preference for WO was observed.
CONCLUSIONS: Novice operators preferred nickel-titanium instruments to stainless
steel, and majority of them opted for reciprocating file instead of continuous
rotating system.
PMID- 27508159
TI - Proximity of the mandibular molar root apex from the buccal bone surface: a cone
beam computed tomographic study.
AB - OBJECTIVES: The purpose of this study was to evaluate the proximity of the
mandibular molar apex to the buccal bone surface in order to provide anatomic
information for apical surgery. MATERIALS AND METHODS: Cone-beam computed
tomography (CBCT) images of 127 mandibular first molars and 153 mandibular second
molars were analyzed from 160 patients' records. The distance was measured from
the buccal bone surface to the root apex and the apical 3.0 mm on the cross
sectional view of CBCT. RESULTS: The second molar apex and apical 3 mm were
located significantly deeper relative to the buccal bone surface compared with
the first molar (p < 0.01). For the mandibular second molars, the distance from
the buccal bone surface to the root apex was significantly shorter in patients
over 70 years of age (p < 0.05). Furthermore, this distance was significantly
shorter when the first molar was missing compared to nonmissing cases (p < 0.05).
For the mandibular first molars, the distance to the distal root apex of one
distal-rooted tooth was significantly greater than the distance to the disto
buccal root apex (p < 0.01). In mandibular second molar, the distance to the apex
of C-shaped roots was significantly greater than the distance to the mesial root
apex of non-C-shaped roots (p < 0.01). CONCLUSIONS: For apical surgery in
mandibular molars, the distance from the buccal bone surface to the apex and
apical 3 mm is significantly affected by the location, patient age, an adjacent
missing anterior tooth, and root configuration.
PMID- 27508160
TI - In vitro evaluation of a newly produced resin-based endodontic sealer.
AB - OBJECTIVES: A variety of root canal sealers were recently launched to the market.
This study evaluated physicochemical properties, biocompatibility, and sealing
ability of a newly launched resin-based sealer (Dia-Proseal, Diadent) compared to
the existing root canal sealers (AHplus, Dentsply DeTrey and ADseal, Metabiomed).
MATERIALS AND METHODS: The physicochemical properties of the tested sealers
including pH, solubility, dimensional change, and radiopacity were evaluated.
Biocompatibility was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. For microleakage test, single-rooted
teeth were instrumented, and obturated with gutta-percha and one of the sealers
(n = 10). After immersion in 1% methylene blue solution for 2 weeks, the
specimens were split longitudinally. Then, the maximum length of staining was
measured. Statistical analysis was performed by one-way analysis of variance
followed by Tukey test (p = 0.05). RESULTS: Dia-Proseal showed the highest pH
value among the tested sealers (p < 0.05). ADseal showed higher dimensional
change compared to AHplus and Dia-Proseal (p < 0.05). The solubility values of
AHplus and Dia-Proseal were similar, whereas ADseal had the lowest solubility
value (p < 0.05). The flow values of sealer in increasing order were AHplus,
DiaProseal, and ADseal (p < 0.05). The radiopacity of AHplus was higher than
those of ADseal and Dia-Proseal (p < 0.05). The cell viability of the tested
materials was statistically similar throughout the experimental period. There
were no significant differences in microleakage values among the tested samples.
CONCLUSIONS: The present study indicates that Dia-Proseal has acceptable
physicochemical properties, biocompatibility, and sealing ability.
PMID- 27508161
TI - Effect of three nanobiomaterials on microhardness of bleached enamel.
AB - OBJECTIVES: The aim of this in vitro study was to evaluate the effect of
incorporating three different nanobiomaterials into bleaching material on
microhardness of bleached enamel. MATERIALS AND METHODS: The crowns of 24
extracted sound human molars were sectioned. Sixty enamel specimens (2 * 3 * 4
mm) were selected and divided into five groups (n = 12): Group 1 received no
bleaching procedure (control); Group 2 underwent bleaching with a 40% hydrogen
peroxide (HP) gel; Groups 3, 4, and 5 were bleached with a 40% HP gel modified by
incorporation of bioactive glass (BAG), amorphous calcium phosphate (ACP) and
hydroxyapatite (HA), respectively. The enamel microhardness was evaluated. The
differences in Knoop microhardness data of each group were analyzed by one-way
ANOVA, followed by post hoc Tukey tests. RESULTS: Significant differences were
observed between the study groups. The enamel microhardness changes in Groups 1,
3, 4, and 5 were significantly lower than that of Group 2 (p < 0.001).
CONCLUSIONS: Within the limitations of this study, it can be concluded that
incorporation of each one of the three tested biomaterials as remineralizing
agents might be effective in decreasing enamel microhardness changes subsequent
to in-office bleaching.
PMID- 27508162
TI - Involvement of TRPA1 in the cinnamaldehyde-induced pulpal blood flow change in
the feline dental pulp.
AB - OBJECTIVES: The purpose of this study was to investigate the involvement of TRPA1
in the cinnamaldehyde-induced pulpal blood flow (PBF) change in the feline dental
pulp. MATERIALS AND METHODS: Mandibles of eight cats were immobilized and PBF was
monitored with a laser Doppler flowmetry at the mandibular canine tooth. To
evaluate the effect of cinnamaldehyde on PBF, cinnamaldehyde was injected into
the pulp through the lingual artery at a constant rate for 60 seconds. As a
control, a mixture of 70% ethanol and 30% dimethyl sulfoxide (DMSO, vehicle) was
used. To evaluate the involvement of transient receptor potential ankyrin 1
(TRPA1) in PBF change, AP18, a specific TRPA1 antagonist, was applied into the
pulp through the Class V dentinal cavity followed by cinnamaldehyde
administration 3 minutes later. The paired variables of experimental data were
statistically analyzed using paired t-test. A p value of less than 0.05 was
considered as statistically significant. RESULTS: Administration of
cinnamaldehyde (0.5 mg/kg, intra-arterial [i.a.]) induced significant increases
in PBF (p < 0.05). While administration of a TRPA1 antagonist, AP18 (2.5 - 3.0
mM, into the dentinal cavity [i.c.]) caused insignificant change of PBF (p >
0.05), administration of cinnamaldehyde (0.5 mg/kg, i.a.) following the
application of AP18 (2.5 - 3.0 mM, i.c.) resulted in an attenuation of PBF
increase from the control level (p < 0.05). As a result, a TRPA1 antagonist, AP18
effectively inhibited the vasodilative effect of cinnamaldehyde (p < 0.05).
CONCLUSIONS: The result of the present study provided a functional evidence that
TRPA1 is involved in the mechanism of cinnamaldehyde-induced vasodilation in the
feline dental pulp.
PMID- 27508163
TI - Esthetic enhancement of a traumatized anterior tooth with a combination of forced
eruption and tooth alignment: a case report.
AB - Exposing sound structure of a subgingivally fractured tooth using orthodontic
extrusion is considered to be a conservative way to re-establish biologic width
without sacrificing esthetics or jeopardizing periodontal support of neighboring
teeth. When a misaligned tooth is traumatically involved, a more comprehensive
approach combining tooth extrusion and re-alignment may be necessary for a
successful restorative outcome. This case report describes a successful esthetic
management of a patient with complicated crown-root fracture on the maxillary
right central incisor and pre-existing malocclusion in the maxillary anterior
region. Forced eruption along with re-alignment of teeth by orthodontic movement
seems to allow re-positioning of the fracture line to a favorable position and
correction of crowding, providing a better esthetic result.
PMID- 27508164
TI - A combined approach to non-carious cervical lesions associated with gingival
recession.
AB - Non-carious cervical lesions (NCCLs) with gingival recession require specific
consideration on both aspects of hard and soft tissue lesion. In the restorative
aspect, careful finishing and polishing of the restorations prior to mucogingival
surgery is the critical factor contributing to success. Regarding surgery,
assessment of the configuration of the lesion and the choice of surgical
technique are important factors. The precise diagnosis and the choice of the
proper treatment procedure should be made on the basis of both restorative and
surgical considerations to ensure the successful treatment of NCCLs.
PMID- 27508165
TI - Application of quantitative light-induced fluorescence to determine the depth of
demineralization of dental fluorosis in enamel microabrasion: a case report.
AB - Enamel microabrasion has become accepted as a conservative, nonrestorative method
of removing intrinsic and superficial dysmineralization defects from dental
fluorosis, restoring esthetics with minimal loss of enamel. However, it can be
difficult to determine if restoration is necessary in dental fluorosis, because
the lesion depth is often not easily recognized. This case report presents a
method for analysis of enamel hypoplasia that uses quantitative light-induced
fluorescence (QLF) followed by a combination of enamel microabrasion with
carbamide peroxide home bleaching. We describe the utility of QLF when selecting
a conservative treatment plan and confirming treatment efficacy. In this case,
the treatment plan was based on QLF analysis, and the selected combination
treatment of microabrasion and bleaching had good results.
PMID- 27508166
TI - Statistical notes for clinical researchers: Sample size calculation 3. Comparison
of several means using one-way ANOVA.
PMID- 27508167
TI - Introducing the GentleWave System.
PMID- 27508168
TI - Nano-computed tomography: current and future perspectives.
PMID- 27508169
TI - Effect of Akimbo versus Raised Arm Positioning on Breast and Cardiopulmonary
Dosimetry in Pediatric Hodgkin Lymphoma.
AB - PURPOSE: In pediatric Hodgkin lymphoma (HL), radiotherapy (RT)-related late
toxicities are a prime concern during treatment planning. This is the first study
to examine whether arm positioning (raised versus akimbo) result in differential
cardiopulmonary and breast doses in patients undergoing mediastinal RT. METHODS:
Two treatment plans were made for each patient (akimbo/arms raised); treatment
was per Children's Oncology Group AHOD0031 protocol, including AP/PA fields. The
anterior midline T6-T7 disk space was used as an anatomic reference of "midline."
Heart/lungs were contoured for each setup. For females, breasts were also
contoured and nipple positions identified. Volumetric centers of contoured organs
were defined and three-dimensional distances from "midline" were computed.
Analyzed dosimetric parameters included V5 (volume receiving >=5 Gy), V10, V15,
V20, and mean dose. Statistics were performed using the Mann-Whitney test.
RESULTS: Fifteen (6 females, 9 males) pediatric HL patients treated with
mediastinal RT were analyzed. The median lateral distance from the breast
center/nipple to "midline" with arms akimbo was larger than that with arms raised
(8.6 vs. 7.7 cm left breast, p = 0.04; 10.7 vs. 9.2 cm left nipple, p = 0.04; 8.7
vs. 7.0 cm right breast, p = 0.004; 9.9 vs. 7.9 cm right nipple, p = 0.007).
Raised arm position was associated with a median 2.8/3.0 cm decrease in
breast/nipple separation, respectively. There were no significant differences in
craniocaudal breast/nipple position based on arm positioning (p > 0.05).
Increasing breast volume was correlated with larger arm position-related changes
in breast/nipple separation (r = 0.74, p = 0.06/r = 0.85, p = 0.02). Akimbo
positioning lowered median breast V5, V10, V15, and mean dose (p < 0.05), with no
differences observed in patients with both mediastinal and axillary disease for
any parameters (p > 0.05). Arm position had no significant effect on
cardiopulmonary doses. CONCLUSION: Akimbo arm positioning may be advantageous to
decrease breast doses in female pediatric HL patients undergoing mediastinal RT,
especially in the absence of axillary disease.
PMID- 27508170
TI - DNA methylation changes and TE activity induced in tissue cultures of barley
(Hordeum vulgare L.).
AB - BACKGROUND: In vitro plant regeneration via androgenesis or somatic embryogenesis
is capable of inducing (epi)mutations that may affect sexual progenies. While
epimutations are associated with DNA methylation, mutations could be due to the
movement of transposons. The common notion is that both processes are linked. It
is being assumed that demethylation activates transposable elements (TEs).
Analysis of methylation changes and their relation with TEs activation in tissue
cultures requires uniquely derived donor plants (Ds), their regenerants (Rs) and
respective progeny (Ps) that would allow discrimination of processes not related
to changes introduced via in vitro cultures. Moreover, a set of methods (RP-HPLC,
SSAP, and MSTD) is needed to study whether different TEs families are being
activated during in vitro tissue culture plant regeneration and whether their
activity could be linked to DNA methylation changes or alternative explanations
should be considered. RESULTS: The in vitro tissue culture plant regeneration in
barley was responsible for the induction of DNA methylation in regenerants and
conservation of the methylation level in the progeny as shown by the RP-HPLC
approach. No difference between andro- and embryo-derived Rs and Ps was observed.
The SSAP and MSTD approach revealed that Ds and Rs were more polymorphic than Ps.
Moreover, Rs individuals exhibited more polymorphisms with the MSTD than SSAP
approach. The differences between Ds, Rs and Ps were also evaluated via ANOVA and
AMOVA. CONCLUSIONS: Stressful conditions during plant regeneration via in vitro
tissue cultures affect regenerants and their sexual progeny leading to an
increase in global DNA methylation of Rs and Ps compared to Ds in barley. The
increased methylation level noted among regenerants remains unchanged in the Ps
as indicated via RP-HPLC data. Marker-based experiments suggest that TEs are
activated via in vitro tissue cultures and that, independently of the increased
methylation, their activity in Rs is greater than in Ps. Thus, the increased
methylation level may not correspond to the stabilization of TEs movement at
least at the level of regenerants. The presence of TEs variation among Ds that
were genetically and epigenetically uniform may suggest that at least some mobile
elements may be active, and they may mask variation related to tissue cultures.
Thus, tissue cultures may activate some TEs whereas the others remain intact, or
their level of movement is changed. Finally, we suggest that sexual reproduction
may be responsible for the stabilization of TEs.
PMID- 27508171
TI - A review on the diagnosis and treatment of hepatocellular carcinoma with a focus
on the role of Wnts and the dickkopf family of Wnt inhibitors.
AB - Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide.
There are multiple etiologic factors including viral and environmental influences
that can lead to HCC. Successful screening for early HCC is challenging due to
the lack of well characterized and specific biomarkers. However, achieving
successful screening is critically important as early diagnosis can potentially
provide curative opportunities. Once HCC is advanced, there are multiple
therapeutic venues, but most eventually fail, therefore developing new targeted
therapies may provide greater chance for effective therapies. Along these lines,
the Wnt pathway has been identified as contributing to the development and
progression of HCC. Wnts can modify HCC growth and invasive ability. A key factor
in the Wnt pathway is the dickkopf (DKK) family of Wnt inhibitors. DKKs have also
been shown to modulate HCC progression. Additionally, several studies have
suggested that DKK expression in tissue and serum has diagnostic and prognostic
value.
PMID- 27508172
TI - Emerging role of insulin-like growth factor-binding protein 7 in hepatocellular
carcinoma.
AB - Hepatocellular carcinoma (HCC) is a vicious and highly vascular cancer with a
dismal prognosis. It is a life-threatening illness worldwide that ranks fifth in
terms of cancer prevalence and third in cancer deaths. Most patients are
diagnosed at an advanced stage by which time conventional therapies are no longer
effective. Targeted molecular therapies, such as the multikinase inhibitor
sorafenib, provide a modest increase in survival for advanced HCC patients and
display significant toxicity. Thus, there is an immense need to identify novel
regulators of HCC that might be targeted effectively. The insulin-like growth
factor (IGF) axis is commonly abnormal in HCC. Upon activation, the IGF axis
controls metabolism, tissue homeostasis, and survival. Insulin-like growth factor
binding protein 7 (IGFBP7) is a secreted protein of a family of low-affinity IGF
binding proteins termed "IGFBP-related proteins" that have been identified as a
potential tumor suppressor in HCC. IGFBP7 has been implicated in regulating
cellular proliferation, senescence, and angiogenesis. In this review, we provide
a comprehensive discussion of the role of IGFBP7 in HCC and the potential use of
IGFBP7 as a novel biomarker for drug resistance and as an effective therapeutic
strategy.
PMID- 27508173
TI - Micro-ribonucleic acids: potential noninvasive biomarkers for hepatocellular
carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most common malignancies globally.
Each year, more than 500,000 people worldwide are diagnosed with HCC. The onset
of HCC is typically unnoticeable, and the prognosis is usually poor. The early
diagnosis of HCC and dynamic monitoring of this disease can contribute to more
effective therapeutic interventions and improve patient outcomes. To achieve
early diagnosis, more sensitive, specific, and easily detectable biomarkers are
necessary. Recently, scientists have focused on identifying novel, sensitive, and
minimally invasive or noninvasive biomarkers. Micro-ribonucleic acids (miRNAs)
are a class of endogenous noncoding single-stranded RNAs that regulate gene
expression at the posttranscriptional level. By negatively regulating target-gene
expression, miRNAs play a critical role in diverse biological processes,
including apoptosis, proliferation, differentiation, and developmental timing.
Unique changes in miRNA expression in serum or plasma samples from HCC patients
have been reported, suggesting that miRNAs may serve as novel noninvasive
biomarkers for diagnosing HCC and evaluating therapeutic responses or as
potential therapeutic targets in HCC. This review focuses on recent progress in
understanding the role of miRNAs in HCC pathogenesis and progression, and
highlights their diagnostic and prognostic value for HCC patients.
PMID- 27508174
TI - Critical analysis of the potential of targeting GPC3 in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths
worldwide. The treatment options for patients with advanced HCC are limited, and
novel treatment strategies are required urgently. Glypican-3 (GPC3), a member of
the glypican family of heparan sulfate proteoglycans, is overexpressed in 72%-81%
of HCC cases, and is correlated with a poor prognosis. GPC3 regulates both
stimulatory and inhibitory signals, and plays a key role in regulating cancer
cell growth. GPC3 is released into the serum, and so might be a useful diagnostic
marker for HCC. GPC3 is also used as an immunotherapeutic target in HCC. A Phase
I study of a humanized anti-GPC3 monoclonal antibody, GC33, revealed a good
safety profile and potential antitumor activity, and a Phase II trial is
currently ongoing. In addition, the authors' investigator-initiated Phase I study
of a GPC3-derived peptide vaccine showed good safety and tolerability, and
demonstrated that the GPC3 peptide-specific cytotoxic T-lymphocyte frequency in
peripheral blood correlated with overall survival in HCC patients. A sponsor
initiated Phase I clinical trial of a three-peptide cocktail vaccine, which
includes a GPC3-derived peptide, is also underway. GPC3 is currently recognized
as a promising therapeutic target and diagnostic marker for HCC. This review
introduces the recent progress in GPC3 research, from biology to clinical impact.
PMID- 27508176
TI - Potential immunotherapeutic role of interleukin-2 and interleukin-12 combination
in patients with hepatocellular carcinoma.
AB - BACKGROUND: Many recent therapeutic interventions are necessary to improve the
treatment of hepatocellular carcinoma (HCC), including immunotherapy, which seems
to offer one of the new realistic therapeutic modalities. This study aims to
investigate the optimization of immunotherapy for HCC patients by appraisal of
both interferon (IFN)-gamma levels and phenotyping of lymphocytes obtained from
peripheral blood and fine-needle aspirates. METHODS: The isolated lymphocytes
were cultured in the presence of interleukins (IL)-2, IL-4, and IL-12. Enzyme
linked immunosorbent assay and flow cytometric techniques were used for the
assessment of human IFN-gamma production and the studied T-cell subpopulations,
respectively. RESULTS: Mixed cell populations of peripheral blood lymphocytes and
tumor infiltrating lymphocytes treated with IL-2 plus IL-12 showed a marked and
significant elevation in IFN-gamma levels in their culture media, a significant
decrease in the percentage of cluster of differentiation (CD)4(+)CD25(+)
regulatory T-cells, and a nonsignificant increase in the percentage of CD8(+)
cytotoxic T-cells. Meanwhile, IL-2 plus IL-4 treatment demonstrated
nonsignificant effects. CONCLUSION: Our data suggested that IL-12 together with
IL-2 caused a suppression of CD4(+)CD25(+) regulatory T-cells and an elevation of
IFN-gamma levels, which play a crucial immunotherapeutic role in the management
of HCC patients.
PMID- 27508175
TI - Fibroblast growth factor family as a potential target in the treatment of
hepatocellular carcinoma.
AB - Hepatocellular cancer (HCC) is currently the third leading cause of cancer death
worldwide. The prognosis of patients diagnosed with late-stage disease is dismal
due to high resistance to conventional systemic therapies. The introduction of
sorafenib, despite its limited efficacy, as the standard systemic therapy for
advanced HCC has paved a way for targeted molecular therapies for HCC. Fibroblast
growth factor (FGF) signaling plays an important role in the developing embryo
and the adult. The FGF signaling pathway is often hijacked by cancer cells,
including HCC. Several alterations in FGF signaling correlate with poor outcome
in HCC patients, suggesting that this family of signaling molecules plays an
important role in the development of HCC. Multikinase inhibitors targeting FGF
signaling are currently under investigation in clinical trials. This review
discusses the current understanding of the biological and clinical implications
of aberrant FGF signaling in the prognosis, diagnosis, and treatment of HCC.
PMID- 27508177
TI - New insights on the role of epigenetic alterations in hepatocellular carcinoma.
AB - Emerging evidence assigns to epigenetic mechanisms heritable differences in gene
function that come into being during cell development or via the effect of
environmental factors. Epigenetic deregulation is strongly involved in the
development of hepatocellular carcinoma (HCC). It includes changes in methionine
metabolism, promoter hypermethylation, or increased proteasomal degradation of
oncosuppressors, as well as posttranscriptional deregulation by microRNA or
messenger RNA (mRNA) binding proteins. Alterations in the methylation of the
promoter of methyl adenosyltransferase MAT1A and MAT2A genes in HCC result in
decreased S-adenosylmethionine levels, global DNA hypomethylation, and
deregulation of signal transduction pathways linked to methionine metabolism and
methyl adenosyltransferases activity. Changes in S-adenosylmethionine levels may
also depend on MAT1A mRNA destabilization associated with MAT2A mRNA
stabilization by specific proteins. Decrease in MAT1A expression has also been
attributed to miRNA upregulation in HCC. A complex deregulation of miRNAs is also
strongly involved in hepatocarcinogenesis, with up-regulation of different miRNAs
targeting oncosuppressor genes and down-regulation of miRNAs targeting genes
involved in cell-cycle and signal transduction control. Oncosuppressor gene down
regulation in HCC is also induced by promoter hypermethylation or
posttranslational deregulation, leading to proteasomal degradation. The role of
epigenetic changes in hepatocarcinogenesis has recently suggested new promising
therapeutic approaches for HCC on the basis of the administration of methylating
agents, inhibition of methyl adenosyltransferases, and restoration of the
expression of tumor-suppressor miRNAs.
PMID- 27508178
TI - Sorafenib in advanced hepatocellular carcinoma: current status and future
perspectives.
AB - The approval of sorafenib, a multikinase inhibitor targeting primarily Raf kinase
and the vascular endothelial growth factor receptor, in 2007 for treating
advanced hepatocellular carcinoma (HCC) has generated considerable enthusiasm in
drug development for this difficult-to-treat disease. However, because several
randomized Phase III studies testing new multikinase inhibitors failed, sorafenib
remains the standard of first-line systemic therapy for patients with advanced
HCC. Field practice studies worldwide have suggested that in daily practice,
physicians are adopting either a preemptive dose modification or a ramp-up
strategy to improve the compliance of their patients. In addition, accumulating
data have suggested that patients with Child-Pugh class B liver function can
tolerate sorafenib as well as patients with Child-Pugh class A liver function,
although the actual benefit of sorafenib in patients with Child-Pugh class B
liver function has yet to be confirmed. Whether sorafenib can be used as an
adjunctive therapy to improve the outcomes of intermediate-stage HCC patients
treated with transcatheter arterial chemoembolization or early-stage HCC patients
after curative therapies is being investigated in several ongoing randomized
Phase III studies. An increasing number of studies have reported that sorafenib
exerts "off-target" effects, including the modulation of signaling pathways other
than Raf/MEK/ERK pathway, nonapoptotic cell death mechanisms, and even immune
modulation. Finally, although sorafenib in combination with chemotherapy or other
targeted therapies has the potential to improve therapeutic efficacy in treating
HCC, it also increases toxicity. Additional clinical studies are warranted to
determine useful sorafenib-based combinations for the treatment of advanced HCC.
PMID- 27508179
TI - Clinical utility of imaging for evaluation of hepatocellular carcinoma.
AB - The hemodynamics of a hepatocellular nodule is the most important imaging
parameter used to characterize various hepatocellular nodules in liver cirrhosis,
because sequential changes occur in the feeding vessels and hemodynamic status
during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular
carcinoma (HCC) are also usually based on vascular findings, eg, early arterial
uptake followed by washout in the portal venous and equilibrium phases. Contrast
enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT),
and dynamic magnetic resonance (MR) imaging with gadopentetate dimeglumine (Gd
DTPA) are useful for detecting hypervascular HCC on the basis of vascular
criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging
with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA), a
hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR
imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC.
Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically
differentiated HCC as hypointense relative to the liver parenchyma. (18)F
fluorodeoxyglucose positron emission tomography imaging might not be suitable for
the screening and detection of HCC, given its lower diagnostic performance.
However, this technique plays an important role in determining whether HCC has
spread beyond the liver.
PMID- 27508180
TI - Telaprevir-containing regimen for treatment of hepatitis C virus infection in
patients with hepatocellular carcinoma awaiting liver transplantation: a case
series.
AB - In patients who undergo liver transplantation (LT), allograft failure secondary
to hepatitis C virus (HCV) recurrence after LT accounts for two-thirds of graft
failures and deaths. Achievement of sustained virologic response before LT
eliminates the risk of HCV recurrence. Only a limited number of studies have
evaluated the role of antiviral treatment before LT. No published data are
available regarding the use of HCV protease inhibitors before LT. We report our
experience using the combination of telaprevir, pegylated interferon alfa-2a
(PegIFN alfa-2a), and ribavirin in three patients with HCV-associated
hepatocellular carcinoma (HCC) awaiting LT. Two patients had not received, and
one had had a partial response to HCV therapy (PegIFN alfa-2a plus ribavirin).
All three patients had genotype 1b and were started on telaprevir and full doses
of PegIFN alfa-2a and ribavirin. Treatment was planned to be continued until the
day of LT or 48 weeks total, whichever came first. One patient still had
detectable HCV RNA after 24 weeks of antivirals and was, therefore, excluded from
further analysis. The other two patients had undetectable HCV RNA at the end of
antiviral therapy. In one of these patients, HCV RNA remained undetectable after
LT; the other patient experienced viral relapse. HCV therapy was tolerated by all
patients; no patient required permanent discontinuation of therapy because of
toxic effects. All three patients experienced hematologic toxic effects. Only one
patient required treatment discontinuation, due to progression of HCC. The use of
telaprevir-containing regimens appears to be safe in selected patients with HCV
associated HCC awaiting LT, but more studies are warranted to evaluate the safety
and efficacy of this treatment combination to prevent post-LT viral recurrence.
PMID- 27508181
TI - Hepatocellular carcinoma: epidemiology and risk factors.
AB - Hepatocellular carcinoma is one of the major malignant tumors in the world today.
The number of new cases of the tumor increases year by year, and hepatocellular
carcinoma almost always runs a fulminant course and carries an especially grave
prognosis. It has a low resectability rate and a high recurrence rate after
surgical intervention, and responds poorly to anticancer drugs and radiotherapy.
Hepatocellular carcinoma does not have a uniform geographical distribution:
rather, very high incidences occur in Eastern and Southeastern Asia and in sub
Saharan Black Africans. In these regions and populations, the tumor shows a
distinct shift in age distribution toward the younger ages, seen to greatest
extent in sub-Saharan Black Africans. In all populations, males are more commonly
affected. The most common risk factors for hepatocellular carcinoma in resource
poor populations with a high incidence of the tumor are chronic hepatitis B virus
infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These
two causative agents act either singly or synergistically. Both the viral
infection and exposure to the fungus occur from early childhood, and the tumor
typically presents at an early age. Chronic hepatitis C virus infection is an
important cause of hepatocellular carcinoma in resource-rich countries with a low
incidence of the tumor. The infection is acquired in adulthood and hepatocellular
carcinoma occurs later than it does with hepatitis B virus-induced tumors. In
recent years, obesity and the metabolic syndrome have increased markedly in
incidence and importance as a cause of hepatocellular carcinoma in some resource
rich regions. Chronic alcohol abuse remains an important risk factor for
malignant transformation of hepatocytes, frequently in association with alcohol
induced cirrhosis. Excessive iron accumulation in hereditary hemochromatosis and
dietary iron overload in the Black African population and membranous obstruction
of the inferior cava cause the tumor in a few countries.
PMID- 27508182
TI - Emerging role of the peroxisome proliferator-activated receptor-gamma in
hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the major leading cause of cancer death
worldwide. Hepatitis B virus, hepatitis C virus, alcohol consumption, non
alcoholic fatty liver disease, and diabetes are the major risks for developing
HCC. Until now, recurrence and metastasis are the major cause of death in HCC
patients. Therefore, identification of new effective molecular targets is an
urgent need for treatment of HCC. Peroxisome proliferator-activated receptor
gamma (PPARgamma) is a ligand-activated nuclear receptor which could be activated
by PPARgamma agonists such as thiazolidinediones, and natural PPARgamma ligand
(such as 15-deoxy-Delta12,14-prostaglandin J2, 15d-PGJ2). Increasing in vitro and
in vivo evidence has demonstrated that PPARgamma agonists exhibit an inhibitory
role on tumor cell growth, migration, and invasion, suggesting that PPARgamma
activation may play an important role in the regulation of growth of HCC. It has
been reported that PPARgamma activation by thiazolidinediones or overexpression
of PPARgamma by virus-mediated gene transfer has shown growth inhibitory effects
in hepatoma cells, but the expression level of PPARgamma in HCC tissues still
remains conflicting. Notably, a novel PPARgamma agonist, honokiol, has recently
been found to activate the PPARgamma/RXR heterodimer, and has also exhibited
significant anti-cancer effects in hepatoma cells. In the present review, we
summarized studies on the role and the molecular regulation of PPARgamma in HCC
development in vitro and in vivo. PPARgamma has the potential to be a therapeutic
target for future treatment of HCC.
PMID- 27508183
TI - Radiological diagnosis of hepatocellular carcinoma.
AB - Diagnosis of hepatocellular carcinoma (HCC) still remains a challenging issue. In
the setting of liver cirrhosis, international guidelines have set the noninvasive
criteria for HCC diagnosis, represented by the detection of contrast
hyperenhancement in the arterial phase (wash-in) and hypoenhancement in the
portal or delayed phase (wash-out) with dynamic multi-detector computer
tomography or magnetic resonance (MR) imaging. Although highly specific, this
typical enhancement pattern has relatively low sensitivity, since approximately
one-third of HCC nodules are characterized by atypical enhancement patterns. In
atypical HCC nodules larger than 1 cm, the majority of international guidelines
recommend liver biopsy. However, there is an increasing interest in exploiting
new noninvasive diagnostic tools, to increase the sensitivity of radiological
diagnosis of HCC. Diffusion-weighted MR imaging and MR hepatobiliary contrast
agents may represent useful tools for the detection and characterization of
borderline hypovascular lesions by providing functional information such as water
molecule motion in diffusion-weighted imaging and residual hepatobiliary
function, which can be impaired early during the course of hepatocarcinogenesis.
Also, dual-energy computed tomography (CT) represents an interesting new CT
technology that could increase detectability and conspicuity of hypervascular
lesions, thus possibly improving CT sensitivity in small HCCs. However, more data
and further developments are needed to verify the usefulness of these new
technologies in the diagnosis of HCC and to translate these recent advances into
clinical practice.
PMID- 27508184
TI - Potent efficacy signals from systemically administered oncolytic herpes simplex
virus (HSV1716) in hepatocellular carcinoma xenograft models.
AB - Oncolytic herpes simplex virus (HSV1716), lacking the neurovirulence factor
ICP34.5, has highly selective replication competence for cancer cells and has
been used in clinical studies of glioma, melanoma, head and neck squamous cell
carcinoma, pediatric non-central nervous system solid tumors, and malignant
pleural mesothelioma. To date, 88 patients have received HSV1716 and the virus is
well tolerated, with selective replication in tumor cells and no spread to
surrounding normal tissue. We assessed the potential value of HSV1716 in
preclinical studies with two human hepatocellular carcinoma cell lines, HuH7 and
HepG2-luc. HSV1716 displayed excellent replication kinetics in vitro in HepG2-luc
cells, a cell line engineered to express luciferase, and virus-mediated cell
killing correlated with loss of light emissions from the cells. In vivo, the
HepG2-luc cells readily formed light-emitting xenografts that were easily
visualized by an in vivo imaging system and efficiently eliminated by HSV1716
oncolysis after intratumoral injection. HSV1716 also demonstrated strong efficacy
signals in subcutaneous HuH7 xenografts in nude mice after intravenous
administration of virus. In the HuH7 model, the intravenously injected virus
replicated prolifically immediately after efficient tumor localization, resulting
in highly significant reductions in tumor growth and enhanced survival. Our
preclinical results demonstrate excellent tumor uptake of HSV1716, with prolific
replication and potent oncolysis. These observations warrant a clinical study of
HSV1716 in hepatocellular carcinoma.
PMID- 27508186
TI - Emerging role of dual antiplatelet therapy in the prevention of hepatitis B virus
associated hepatocellular carcinoma.
AB - Platelets, the chief effectors of vascular homeostasis, have been identified as
important players in the pathogenesis of both acute and chronic liver disease in
preclinical models of hepatitis B viral infection. Platelets are thought to
promote the accumulation of virus-specific T-cells into the liver parenchyma.
Importantly, the inhibition of platelet activation by clinically relevant doses
of aspirin and clopidogrel was able to reduce immune-mediated necroinflammatory
liver disease, extracellular matrix deposition, and hepatocellular carcinoma
development; the same treatment was able to improve overall survival. These
results strongly support the design of clinical trials aiming to define the
potential of antiplatelet therapy in the prevention of hepatitis B virus
associated hepatocellular carcinoma.
PMID- 27508185
TI - Transarterial radioembolization using yttrium-90 microspheres in the treatment of
hepatocellular carcinoma: a review on clinical utility and developments.
AB - A selective intra-arterial liver injection using yttrium-90-loaded microspheres
as sources for internal radiation therapy is a form of transarterial
radioembolization (TARE). Current data from the literature suggest that TARE is
effective in hepatocellular carcinoma (HCC) and is associated with a low rate of
adverse events; however, they are all based on retrospective series or non
controlled prospective studies, since randomized controlled trials comparing the
other liver-directed therapies for intermediate and locally advanced stages HCC
are still ongoing. The available data show that TARE provides similar or even
better survival rates. TARE is very well tolerated and has a low rate of
complications; these complications do not result from the embolic effects but
mainly from the unintended irradiation to non-target tissue, including the liver
parenchyma. The complications can be further reduced by accurate patient
selection and a strict pre-treatment evaluation, including dosimetry and
assessment of the vascular anatomy. First-line TARE is best indicated for
intermediate-stage patients (according to the Barcelona Clinic Liver Cancer
[BCLC] staging classification) who are poor candidates for transarterial
chemoembolization or patients having locally advanced disease with segmental or
lobar branch portal vein thrombosis. Moreover, data are emerging regarding the
use of TARE in patients classified slightly above the criteria for liver
transplantation with the purpose of downstaging them. TARE can also be applied as
a second-line treatment in patients progressing to transarterial
chemoembolization or sorafenib; a large number of Phase II/III trials are in
progress in order to evaluate the best association with systemic therapies. Given
the complexity of a correct treatment algorithm for potential TARE candidates and
the need for clinical guidance, a comprehensive review was carried out analyzing
both the best selection criteria of patients who really benefit from TARE and the
new advances of this therapy which add significant value to the therapeutic
weaponry against HCC.
PMID- 27508187
TI - Chemoembolization with drug-eluting microspheres (DEM-TACE) for hepatocellular
carcinoma: single-center review of safety and efficacy.
AB - PURPOSE: This study examines the safety and efficacy of transarterial
chemoembolization using doxorubicin-loaded 30-60 um QuadraSphere microspheres
(DEM-TACE) for the treatment of hepatocellular carcinoma. MATERIALS AND METHODS:
Over 10 weeks, patients with hepatocellular carcinoma. (Child-Pugh A/B: 65%/35%)
were embolized with 30-60 um QuadraSphere microspheres. Excluded patients had
previous locoregional therapy, macrovascular invasion, extrahepatic disease,
Child-Pugh score >B7, ECOG performance status >0, and total bilirubin >3 mg/dL.
Technical success, minor and major complications, 30-day hospital readmission
rate, and 30-day mortality were assessed. alpha-Fetoprotein levels before and
after treatment were compared. Local response was evaluated by radiologic tumor
response per modified Response Evaluation Criteria in Solid Tumors 1 month after
treatment. RESULTS: Thirty tumors (mean size, 2.3 cm; range, 1.0-4.9 cm) were
treated in 20 patients (16 male and 4 female; mean age, 64.7 years). There were
no major complications. Thirty-day mortality was 0%. Minor complications included
postembolization syndrome in 16.7% of cases and transient rise in liver enzymes
requiring no therapy. Mean alpha-fetoprotein levels trended down following
treatment (71.8+/-201.9 ng/mL vs 53.4+/-116.7 ng/mL), but were not statistically
significant. Complete response was achieved in 30% of patients, partial response
in 35%, stable disease in 30%, and progression of disease in 5%. Overall
objective response was 65%. Mean follow-up was 10.4 months (range, 2-16.4
months). CONCLUSION: DEM-TACE with doxorubicin-loaded 30-60 um QuadraSpheres is
feasible, well tolerated, and associated with promising tumor response in early
and intermediate stage disease.
PMID- 27508188
TI - Welcome to Journal of Hepatocellular Carcinoma.
PMID- 27508189
TI - Untreated hepatocellular carcinoma in Egypt: outcome and prognostic factors.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer worldwide as well
as in Egypt with hepatitis C and B, alcohol and aflatoxins being the commonest
risk factors. AIM: The objective of this study was to assess the prognostic
factors affecting overall survival (OS) of untreated HCC in Egypt. METHODS: This
retrospective study was conducted at Tanta Cancer Center, Egypt where 288 HCC
cases who received no specific therapy and were followed-up until death were
identified. The impact of possible prognostic factors on OS was assessed using
the log-rank test (univariate analyses) and Cox regression method (multivariate
analysis). RESULTS: The median OS of untreated HCC was 2.3 months (95% confidence
interval: 1.9-2.6). The 1, 3, 6, 12, 24 months OS rates were 84%, 42%, 21%, 9%,
and 3%, respectively. All cases had died by 46 months. Male sex, advanced Child
Pugh class, the clinical presentation of ascites, cough, fatigue, and the
presence of metastases were associated with poor survival (P<0.05 for all). In
multivariate analysis; cough, presence of ascites, and Child-Pugh class were
independent predictors of poor survival. CONCLUSION: OS in untreated HCC in Egypt
is very short. Many factors interact to produce this dismal survival.
PMID- 27508190
TI - Emerging role of Toll-like receptor 4 in hepatocellular carcinoma.
AB - Toll-like receptor (TLR) signaling has been implicated in inflammatory-related
cancers. The upregulation of TLR signaling in hepatocellular carcinoma (HCC)
suggests that it may play an essential role in the prognosis of chronic and
inflammatory diseases that ultimately culminate in HCC. Here, we provide evidence
about the involvement of the TLR pathway in the initiation, progression, and
metastasis of HCC. The differential expression of TLR in epithelial cells has
also been discussed. In particular, we emphasize the physiological role of TLR4
in the development and pathogenesis of HCC and propose novel and promising
approaches for HCC therapeutics with the aid of TLR ligands.
PMID- 27508191
TI - A clinical perspective of the link between metabolic syndrome and hepatocellular
carcinoma.
AB - Metabolic syndrome (MS), which is defined as a constellation of clinico
biological features closely related to insulin-resistance has reached epidemic
levels in Western Europe and Northern America. Non-alcoholic fatty liver disease
(NAFLD) represents the hepatic manifestation of MS. As its incidence parallels
that of MS, NAFLD is currently becoming one of the most frequent chronic liver
diseases in Western countries. On one hand, MS favors the development of
hepatocellular carcinoma (HCC) either through NAFLD liver parenchymal alterations
(steatosis; steatohepatitis; fibrosis), or in the absence of significant
underlying liver parenchyma changes. In this setting, HCC are often diagnosed
incidentally, tend to be larger than in patients developing HCC on cirrhosis and
therefore frequently require major liver resections. On the other hand, MS
patients are at increased risk of both liver-related postoperative complications
and increased cardiorespiratory events leading to non-negligible mortality rates
following liver surgery. These deleterious effects seem to be related to the
existence of impaired liver function even in the absence of severe fibrosis but
also higher cardiorespiratory sensitivity in a setting of MS/NAFLD. Hence,
specific medical and surgical improvements in the perioperative management of
these patients are required. These include complete preoperative
cardiorespiratory work-up and the wide use of preoperative liver volume
modulation. Finally, the long-term prognosis after curative surgery for MS
related HCC does not seem to be worse than for other HCC occurring on classical
chronic liver diseases. This is probably related to less aggressive tumor
behavior with lower micro vascular invasion and decreased rates of poorly
differentiated lesions. In this setting, several medical therapies including
metformin could be of value in the prevention of both occurrence and recurrence
of HCC.
PMID- 27508192
TI - c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular
carcinoma.
AB - c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as
scatter factor or tumor cytotoxic factor, a mitogenic growth factor for
hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly
acts on neighboring epidermal and endothelial cells, regulating epithelial growth
and morphogenesis. HGF/MET signaling has been identified among the drivers of
tumorigenesis in human cancers. As such, c-MET is a recognized druggable target,
and against it, targeted agents are currently under clinical investigation. c-MET
overexpression is a common event in a wide range of human malignancies, including
gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas.
Despite c-MET overexpression being reported by a large majority of studies, no
evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma
(HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5%
of cases while no mutation has been identified in c-MET oncogene in HCC. Thus,
the selection of patient subgroups more likely to benefit from c-MET inhibition
is challenging. Notwithstanding, c-MET overexpression was reported to be
associated with increased metastatic potential and poor prognosis in patients
with HCC, providing a rationale for its therapeutic inhibition. Here we summarize
the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the
implications for therapeutic approaches in HCC.
PMID- 27508193
TI - Early alpha-fetoprotein response predicts survival in patients with advanced
hepatocellular carcinoma treated with sorafenib.
AB - BACKGROUND: It is not clear whether tumor marker responses can predict survival
during sorafenib treatment in hepatocellular carcinoma (HCC). We investigated
whether the alpha-fetoprotein (AFP) response is associated with survival in
patients with advanced HCC treated with sorafenib. METHODS: We retrospectively
reviewed the records of 126 patients with advanced HCC treated with sorafenib
between 2007 and 2012. An AFP response was defined as >20% decrease from
baseline. At 6-8 weeks after commencing sorafenib, AFP and radiological responses
were assessed by modified Response Evaluation Criteria in Solid Tumors. RESULTS:
The median overall survival (OS) and progression-free survival (PFS) were 6.2 and
3.5 months, respectively. Of the study population, a partial response (PR) was
identified in 5 patients (4.0%), stable disease (SD) in 65 patients (51.6%), and
progressive disease (PD) in 57 patients (44.4%), respectively. AFP non-response
was an independent prognostic factor for poor OS (median 10.9 months for AFP
response vs 5.2 months for AFP non-response), together with Child-Pugh B, tumor
diameter >=10 cm, and portal vein invasion (all P<0.05), and PFS (median 5.3
months for AFP response vs 2.9 months for AFP non-response), together with tumor
diameter >=10 cm and portal vein invasion (all P<0.05). SD or PR was more
frequently found in AFP responders than in non-responders (72.1% vs 47.0%,
respectively; P=0.007). In a sub-group with SD, OS (median 12.7 vs 5.8 months,
respectively) and PFS (median 9.1 vs 3.7 months, respectively) were significantly
longer in AFP responders than in non-responders (all P<0.05). CONCLUSION: Early
AFP response may be useful for predicting survival in patients with advanced HCC
treated with sorafenib.
PMID- 27508194
TI - Hepatocellular carcinoma ablation and possible immunity in the age of nanosecond
pulsed electric fields.
PMID- 27508195
TI - Hapten-enhanced overall survival time in advanced hepatocellular carcinoma by
ultro-minimum incision personalized intratumoral chemoimmunotherapy.
AB - PURPOSE: To compare the therapeutic effects of ultra-minimum incision
personalized intratumoral chemoimmunotherapy (UMIPIC) with intratumoral
chemotherapy (ITCT) in the treatment of advanced hepatocellular carcinomas and to
analyze the effect of hapten as an immune booster. MATERIALS AND METHODS:
Patients with advanced hepatocellular carcinomas were treated with UMIPIC or ITCT
with the same therapeutic procedure; the UMIPIC method had a proprietary regimen
including an oxidant, a cytotoxic drug, and hapten, while ITCT delivered the same
drug excluding hapten. Of 339 patients in total, 119 of the UMIPIC patients
(n=214) had response data and 214 had survival data, and of the ITCT patients
(n=125), 61 had response data and 125 had survival data. Tumor response was
assessed with a computed tomography scan 6-8 weeks after the initial treatment;
the survival rate was evaluated by follow-up visits. Tumor size was classified as
small (<5 cm), large (5-10 cm), or very large (>10 cm); tumor sizes with liver
function categorized using Child-Pugh class (A and B) were analyzed by
correlation with overall survival. RESULTS: The response rates (complete response
+ partial response + stable disease) were 78.68% and 81.52% in the UMIPIC and
ITCT groups, respectively, with no statistically significant difference; however,
the median overall survival was 7 months for UMIPIC (test) and 4 months for ITCT
(control), respectively (P<0.01). The 6-month and 1-year survival rates for
UMIPIC and ITCT were 58.88% vs 32.3% and 30.37% vs 13.6%, respectively (P<0.01).
Single and multiple UMIPIC revealed significant improvement in overall survival
compared to that of ITCT. Child-Pugh class A patients had a longer duration of
survival compared to Child-Pugh class B patients in UMIPIC therapy. CONCLUSION:
Hapten had enhanced therapeutic effect with improvement in the survival duration
in UMIPIC compared to ITCT. After reexamination, the response rate was not
different due to inflammation caused by hapten. Hapten has been found to play an
important role in immunotherapy to improve patient survival.
PMID- 27508196
TI - Emerging role of Hpo signaling and YAP in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most
common cause of cancer-related mortality worldwide. Due to the poor prognosis and
limited therapeutic options, there is great interest in further understanding
better the molecular underpinnings and potential molecular targets associated
with HCC. The Hippo (Hpo) signaling pathway and YAP, its principal downstream
effector, represent an innovative area of research in HCC. Pioneered in
Drosophila melanogaster, the Hpo cascade controls tissue homeostasis including
organ size, cell proliferation, apoptosis, as well as cell-cycle regulation and
differentiation. This conserved kinase cascade in mammals depends on central
control by the tumor suppressor mammalian sterile 20-like kinase 1/2 (Mst1/2).
The Mst1/2 commences the downstream kinase cascade, ultimately activating the
oncoprotein YAP and allowing its physical association with downstream targets to
enhance the gene expression signatures that are involved in proliferation and
survival. Alterations in YAP expression and defective regulation of other key Hpo
pathway members, such as Mst1/2, Salvador, neurofibromatosis and Mer (Nf2/mer),
large tumor suppressor homolog 1/2 (Lats1/2), and Mps one binder kinase activator
like 1A and 1B (Mob1) drive carcinogenesis in animal models. The dysregulation of
the Hpo pathway - resulting in an unchecked activation of YAP - culminates in the
development of a broad range of human tumor types, including HCC. The abrogation
of Mst1/2-mediated YAP phosphorylation permits YAP entry into the nucleus in
murine models and functions similarly in human HCCs. Chemoresistance mechanisms
displayed by HCC tumors occur in a YAP-dependent manner. The HCC specimens
exhibit YAP overexpression, and YAP serves as an independent prognostic marker
for disease-free survival and overall survival in patients with HCC. Recently,
the small molecule inhibitor, verteporfin has been shown to attenuate YAP
activity in murine models, perhaps offering a novel therapeutic approach for
patients with advanced HCC.
PMID- 27508197
TI - Ambovex((r)) as a novel immunological modulator drug for the treatment of
hepatocellular carcinoma (HCC) in the liver: a Phase II clinical trial.
AB - Hepatocellular carcinoma (HCC) is a global public health problem, based on it
being the fifth most common cancer and third leading cause of cancer-related
mortality worldwide. The approved conventional treatment methods for HCC have
shown life-threatening side effects with limited or negligible success,
especially in multifocal HCC. As a consequence, new therapeutic approaches are
being explored, including immunoregulatory molecules that may have the potential
to treat or delay the progression of HCC. A novel pharmaceutical botanical drug -
Ambovex((r)), an immune-modulator molecule - was tested to treat or delay the
progress of HCC. We conducted a 6-month randomized clinical trial with an
additional 3-month washing period (no treatment) to evaluate the safety and
efficacy of low-dose Ambovex oral spray in treating patients with HCC. The
clinical study involved a total of 40 patients, with 33 in the treatment group
and seven in the control group. The alpha-fetoprotein (AFP) levels were measured
every month and ultrasound scans were performed at time zero and every 2 months
thereafter. Computed tomography (CT) scans were performed for patients in the
treatment group. Ambovex proved to be safe, as there were no significant side
effects although some patients found that the drug has unpleasant taste. AFP
analysis showed a significant decrease in its level (alpha=0.05; 95% confidence
interval) in the treatment group when compared to the control group at 3 months
(P=0.0031) and at 6 months (P=0.007). The ultrasound results showed improvement
in the treated group, as evidenced by a significant decrease in the lesion
numbers and sizes. The lesions in 38% of treated patients decreased from multiple
to single with major improvements; 35% of patients exhibited a decrease from
multiple lesions to multiple lesions with minor improvements, whereas 27% had
stabilized lesions. CT scans in the treated group showed significant improvement,
as there was complete disappearance of the lesions after 6 months of treatment
with Ambovex in two patients. This clinical study showed the effective and
promising results of Ambovex as an immunological modulator in treating HCC.
Further exploration of Ambovex is recommended.
PMID- 27508198
TI - The androgen receptor as an emerging target in hepatocellular carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the male-dominant liver diseases with
poor prognosis, although treatments for HCC have been progressing in the past
decades. Androgen receptor (AR) is a member of the nuclear receptor superfamily.
Previous studies reported that AR was expressed in human HCC and non-HCC tissues.
AR is activated both ligand-dependently and ligand-independently. The latter is
associated with a mitogen-activated protein kinase-, v-akt murine thymoma viral
oncogene homolog 1-, or signal-transducer and activator of transcription
signaling pathway, which has been implicated in the development of HCC. It has
been reported that more than 200 RNA expression levels are altered by androgen
treatment. In the liver, androgen-responsive genes are cytochrome P450s,
transforming growth factor beta, vascular endothelial growth factor, and glucose
regulated protein 78 kDa, which are also associated with human
hepatocarcinogenesis. Recent studies also revealed that AR plays a role in cell
migration and metastasis. It is possible that cross-talk among AR-signaling,
endoplasmic reticulum stress, and innate immune response is important for human
hepatocarcinogenesis and HCC development. This review shows that AR could play a
potential role in human HCC and represent one of the important target molecules
for the treatment of HCC.
PMID- 27508200
TI - Whither alpha-FP in the diagnosis of hepatocellular carcinoma?
PMID- 27508199
TI - State-of-the-art cross-sectional liver imaging: beyond lesion detection and
characterization.
AB - Cross-sectional imaging with computed tomography or magnetic resonance imaging is
routinely used to detect and diagnose liver lesions; however, these examinations
can provide additional important information. The improvement of equipment and
techniques has allowed outstanding evaluation of the vascular and biliary
anatomy, which is practicable in most routine examinations. Anatomical variants
may exclude patients from certain therapeutic options and may be the cause of
morbidity or mortality after surgery or interventional procedures. Diffuse liver
disease, such as steatosis, hemochromatosis, or fibrosis, must be diagnosed and
quantified. Usually these conditions are silent until the late stages, and
imaging plays an important role in detecting them early. Additionally, a
background of diffuse disease may interfere in a focal lesion systematic
reasoning. The diagnostic probability of a particular nodule varies according to
the background liver disease. Nowadays, most diffuse liver diseases can be easily
and accurately quantified by imaging, which has allowed better understanding of
these diseases and improved patient management. Finally, cross-sectional imaging
can calculate total and partial liver volumes and estimate the future liver
remnant after hepatectomy. This information helps to select patients for portal
vein embolization and reduces postoperative complications. Use of a specific
hepatic contrast agent on magnetic resonance imaging, in addition to improving
detection and characterization of focal lesions, provides functional global and
segmental information about the liver parenchyma.
PMID- 27508201
TI - Transarterial chemoembolization for hepatocellular carcinoma: an evidence-based
review of its place in therapy.
AB - Transarterial chemoembolization (TACE) is the standard treatment for patients
with Barcelona Clinic Liver Cancer-intermediate stage hepatocellular carcinoma
(HCC). The concept of drug-eluting bead TACE builds on the rationale of
intratumoral drug delivery, and drug-eluting bead TACE has been shown to provide
consistent and reliable results and to significantly diminish systemic drug
exposure, liver toxicity, and drug-related adverse events as compared with
conventional TACE. Based on the belief that combinations of TACE and other local
or systemic therapies have several theoretical advantages, many clinical trials
have been conducted to evaluate the effectiveness of TACE in combination with
local treatment such as radiofrequency ablation or radiotherapy, and systemic
therapy such as sorafenib or another molecular therapy. TACE has also been used
as a preoperative adjuvant chemotherapy in patients with HCC to improve survival
and as a bridging therapy before liver transplantation to downstage HCC. In the
present evidence-based review, the authors summarize the current status of these
transcatheter arterial embolic therapies in HCC.
PMID- 27508203
TI - Role of endoscopic ultrasound in diagnosis and management of hepatocellular
carcinoma.
AB - Hepatocellular carcinoma (HCC) is an aggressive tumor and a leading cause of
cancer-related deaths globally. The mortality rate remains high despite many
advances in treatment. HCC is frequently diagnosed late in its course due to lack
of classical symptoms at earlier stages. Endoscopic ultrasound (EUS) has emerged
as an important diagnostic tool for the diagnostic evaluation, staging, and
treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration
has been a valuable addition to EUS by being able to obtain tissue under direct
visualization. Here, we review the potential role of EUS in the diagnosis and
management of HCC. EUS seems to be a safe and reliable alternative method for
obtaining tissue for diagnosis of liver cancer, especially for lesions that are
inaccessible by traditional methods. EUS could play an important role in the
diagnosis and management of HCC.
PMID- 27508202
TI - Type I insulin-like growth factor as a liver reserve assessment tool in
hepatocellular carcinoma.
AB - Chronic liver diseases (CLDs) encompass a wide range of illnesses, including
nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and viral
hepatitis. Deterioration of liver capacity, with subsequent progression into
cirrhosis and hepatocellular carcinoma (HCC), ultimately leads to a further
decrease in the hepatic reserve. The Child-Turcotte-Pugh scoring system is the
standard tool for assessing underlying liver reserve capacity in routine practice
and in clinical trials of CLD and HCC. In this review, we highlight the clinical
significance of insulin-like growth factor-I (IGF-I) and the growth hormone (GH)
signaling pathway in HCC. IGF-I could be a marker for liver reserve capacity in
CLDs and HCC in clinical practice. This approach could improve the risk
assessment and stratifications of patients on the basis of their underlying liver
reserve, either before active treatment in routine practice or before they are
enrolled in clinical trials.
PMID- 27508204
TI - Fibrolamellar hepatocellular carcinoma: current clinical perspectives.
AB - Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC),
which comprises ~1%-9% of all HCCs. Although FLC is a variant of HCC, it is
distinct from HCC in that it most often affects younger patients (10-35 years of
age) with no underlying liver disease. FLC often presents with vague abdominal
pain, nausea, abdominal fullness, malaise, and weight loss. Surgery is the
current mainstay of treatment for FLC and remains the only potentially curative
option. While FLCs are considered less responsive to chemotherapy than their
classic HCC counterparts, there have been suggestions that multimodality
treatments may be effective, especially in advanced cases. Further research is
necessary to determine effective systemic therapies as an adjunct to surgery for
FLC.
PMID- 27508205
TI - Comparing Outcomes of Two Types of Bariatric Surgery in an Adolescent Obese
Population: Roux-en-Y Gastric Bypass vs. Sleeve Gastrectomy.
AB - BACKGROUND: Obesity is prevalent among adolescents and is associated with serious
health consequences. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG)
are bariatric procedures that cause significant weight loss in adults and are
increasingly being performed in adolescents with morbid obesity. Data comparing
outcomes of RYGB vs. SG in this age-group are scarce. This study aims to compare
short-term (1-6 months) and longer-term (7-18 months) body mass index (BMI) and
biochemical outcomes following RYGB and SG in adolescents/young adults. METHODS:
A retrospective study using data extracted from medical records of patients 16-21
years who underwent RYGB or SG between 2012 and 2014 at a tertiary care academic
medical center. RESULTS: Forty-six patients were included in this study: 24
underwent RYGB and 22 underwent SG. Groups did not differ for baseline age, sex,
race, or BMI. BMI reductions were significant at 1-6 months and 7-18 months
within groups (p < 0.0001), but did not differ by surgery type (p = 0.65 and
0.09, for 1-6 months and 7-18 months, respectively). Over 7-18 months, within
group improvement in low-density lipoprotein (LDL) (-24 +/- 6 in RYGB, p = 0.003,
vs. -7 +/- 9 mg/dl in SG, p = 0.50) and non-high-density lipoprotein (non-HDL)
cholesterol (-23 +/- 8 in RYGB, p = 0.02, vs. -12 +/- 7 in SG, p = 0.18) appeared
to be of greater magnitude following RYGB. However, differences between groups
did not reach statistical significance. When divided by non-alcoholic
steatohepatitis stages (NASH), patients with Stage II-III NASH had greater
reductions in alanine aminotransferase levels vs. those with Stage 0-I NASH (-45
+/- 18 vs. -9 +/- 3, p = 0.01) after 7-18 months. RYGB and SG groups did not
differ for the magnitude of post-surgical changes in liver enzymes. CONCLUSION:
RYGB and SG did not differ for the magnitude of BMI reduction across groups,
though changes trended higher following RYGB. Further prospective studies are
needed to confirm these findings.
PMID- 27508206
TI - New Insights into How Trafficking Regulates T Cell Receptor Signaling.
AB - There is emerging evidence that exocytosis plays an important role in regulating
T cell receptor (TCR) signaling. The trafficking molecules involved in lytic
granule (LG) secretion in cytotoxic T lymphocytes (CTL) have been well-studied
due to the immune disorder known as familial hemophagocytic lymphohistiocytosis
(FHLH). However, the knowledge of trafficking machineries regulating the
exocytosis of receptors and signaling molecules remains quite limited. In this
review, we summarize the reported trafficking molecules involved in the transport
of the TCR and downstream signaling molecules to the cell surface. By combining
this information with the known knowledge of LG exocytosis and general exocytic
trafficking machinery, we attempt to draw a more complete picture of how the TCR
signaling network and exocytic trafficking matrix are interconnected to
facilitate T cell activation. This also highlights how membrane
compartmentalization facilitates the spatiotemporal organization of cellular
responses that are essential for immune functions.
PMID- 27508207
TI - Increased Ghrelin but Low Ghrelin-Reactive Immunoglobulins in a Rat Model of
Methotrexate Chemotherapy-Induced Anorexia.
AB - BACKGROUND AND AIMS: Cancer chemotherapy is commonly accompanied by mucositis,
anorexia, weight loss, and anxiety independently from cancer-induced anorexia
cachexia, further aggravating clinical outcome. Ghrelin is a peptide hormone
produced in gastric mucosa that reaches the brain to stimulate appetite. In
plasma, ghrelin is protected from degradation by ghrelin-reactive immunoglobulins
(Ig). To analyze possible involvement of ghrelin in the chemotherapy-induced
anorexia and anxiety, gastric ghrelin expression, plasma levels of ghrelin, and
ghrelin-reactive IgG were studied in rats treated with methotrexate (MTX).
METHODS: Rats received MTX (2.5 mg/kg, subcutaneously) for three consecutive days
and were killed 3 days later, at the peak of anorexia and weight loss. Control
rats received phosphate-buffered saline. Preproghrelin mRNA expression in the
stomach was analyzed by in situ hybridization. Plasma levels of ghrelin and
ghrelin-reactive IgG were measured by immunoenzymatic assays and IgG affinity
kinetics by surface plasmon resonance. Anxiety- and depression-like behaviors in
MTX-treated anorectic and in control rats were evaluated in the elevated plus
maze and the forced-swim test, respectively. RESULTS: In MTX-treated anorectic
rats, the number of preproghrelin mRNA-producing cells was found increased (by
51.3%, p < 0.001) as well were plasma concentrations of both ghrelin and des-acyl
ghrelin (by 70.4%, p < 0.05 and 98.3%, p < 0.01, respectively). In contrast,
plasma levels of total IgG reactive with ghrelin and des-acyl-ghrelin were
drastically decreased (by 87.2 and 88.4%, respectively, both p < 0.001), and
affinity kinetics of these IgG were characterized by increased small and big Kd,
respectively. MTX-treated rats displayed increased anxiety- but not depression
like behavior. CONCLUSION: MTX-induced anorexia, weight loss, and anxiety are
accompanied by increased ghrelin production and by a decrease of ghrelin-reactive
IgG levels and affinity binding properties. Such changes of ghrelin-reactive IgG
may underlie their decreased ghrelin-transporting capacities compromising ghrelin
orexigenic and anxiolytic effects and contributing to chemotherapy-induced loss
of appetite.
PMID- 27508208
TI - PLS-Based and Regularization-Based Methods for the Selection of Relevant
Variables in Non-targeted Metabolomics Data.
AB - Non-targeted metabolomics constitutes a part of the systems biology and aims at
determining numerous metabolites in complex biological samples. Datasets obtained
in the non-targeted metabolomics studies are high-dimensional due to sensitivity
of mass spectrometry-based detection methods as well as complexity of biological
matrices. Therefore, a proper selection of variables which contribute into group
classification is a crucial step, especially in metabolomics studies which are
focused on searching for disease biomarker candidates. In the present study,
three different statistical approaches were tested using two metabolomics
datasets (RH and PH study). The orthogonal projections to latent structures
discriminant analysis (OPLS-DA) without and with multiple testing correction as
well as the least absolute shrinkage and selection operator (LASSO) with
bootstrapping, were tested and compared. For the RH study, OPLS-DA model built
without multiple testing correction selected 46 and 218 variables based on the
VIP criteria using Pareto and UV scaling, respectively. For the PH study, 217 and
320 variables were selected based on the VIP criteria using Pareto and UV
scaling, respectively. In the RH study, OPLS-DA model built after correcting for
multiple testing, selected 4 and 19 variables as in terms of Pareto and UV
scaling, respectively. For the PH study, 14 and 18 variables were selected based
on the VIP criteria in terms of Pareto and UV scaling, respectively. In the RH
and PH study, the LASSO selected 14 and 4 variables with reproducibility between
99.3 and 100%, respectively. In the light of PLS-based models, the larger the
search space the higher the probability of developing models that fit the
training data well with simultaneous poor predictive performance on the
validation set. The LASSO offers potential improvements over standard linear
regression due to the presence of the constrain, which promotes sparse solutions.
This paper is the first one to date utilizing the LASSO penalized logistic
regression in untargeted metabolomics studies.
PMID- 27508209
TI - Bilateral vertebral artery occlusion without headache in giant cell arteritis.
PMID- 27508210
TI - Early indicators of relapses vs pseudorelapses in neuromyelitis optica spectrum
disorder.
AB - OBJECTIVE: The purpose of this study was to review cases of neuromyelitis optica
spectrum disorder (NMOSD) relapses and pseudorelapses to identify early features
that differentiate between them at onset of symptoms. METHODS: This was a
retrospective analysis of 74 hospitalizations of patients with NMOSD who were
admitted to the Johns Hopkins Hospital for workup and treatment of a presumed
relapse. Standard workup included MRI and blood and urine testing for metabolic
and infectious etiologies. The gold standard for a relapse was defined as new or
worsening symptoms and a change in neurologic examination correlating with a new
or enhancing MRI lesion. A pseudorelapse was a clinical exacerbation with similar
symptoms and signs but the MRI was negative, and workup identified an alternative
cause for the symptoms that, when treated, resulted in the improvement of
neurologic symptoms. Factors considered to be early predictors of relapses vs
pseudorelapses were analyzed using the Fisher test. RESULTS: Among 74 NMOSD
hospitalizations for presumed relapse, 57 were confirmed relapses while 17 had a
negative MRI and an identifiable cause of pseudorelapse. The most common causes
of pseudorelapse were infection, pain, and dysautonomia. The only early predictor
that reliably differentiated relapse from pseudorelapse among this NMOSD patient
population was vision loss (p = 0.039). Race, sex, presentations of weakness,
numbness, and bowel/bladder dysfunction, white blood cell count, and urinary
tract infection were not different among patients with relapses vs
pseudorelapses. CONCLUSIONS: Vision loss in NMOSD is strongly suggestive of a
true relapse vs a pseudorelapse. Pseudorelapses localized to the spinal cord in
patients with previous myelitis presented similarly to true relapses and could
only be ruled out by a negative MRI.
PMID- 27508211
TI - Low-Income First-Time Mothers: Effects of APN Follow-up Using Mobile Technology
on Maternal and Infant Outcomes.
AB - Background. Low-income mothers have greater challenges in accessing health care
services due changes in the health care system and budget cuts. The purpose of
this randomized clinical trial was to test a nurse practitioner (NP) intervention
using cell phone and texting on maternal/infant outcomes. Methods. The sample
included 129 mother-infant pairs. Intervention group mothers received NP 2-way
cell phone follow-up intervention post-hospital discharge for 6 months. Results.
Intervention mothers' perceived social support was significantly higher.
Intervention infants received their first newborn follow-up visit significantly
earlier (6 vs 9 days); significantly more infants were immunized at recommended
times (2, 4, and 6 months of age); and there were fewer infant morbidities
compared to controls. The intervention saved between $51 030 and $104 277 in
health care costs averted. Conclusion. This easy-to-use, safe intervention is an
effective way to reach a wide range of populations and demonstrated improved
maternal/infant outcomes and decreased cost.
PMID- 27508212
TI - Thrombosis of Kommerell's diverticulum with subclavian steal phenomenon in a
patient with non-small cell lung carcinoma under chemotherapy.
AB - Kommerell's diverticulum (KD) is defined as a bulbous dilatation of the origin of
an aberrant subclavian artery due to a remnant of the left fourth aortic arch. We
report the case of an asymptomatic woman in whom progressive thrombosis of the KD
extending to the prevertebral tract of an aberrant right subclavian artery was
detected at multidetector computed tomography imaging for lung cancer staging
performed before and after the beginning of chemotherapy. Reversed blood flow in
the ipsilateral vertebral artery due to subclavian steal phenomenon was also
observed by color Doppler ultrasound examination.
PMID- 27508213
TI - Data correlations between gender, cytomegalovirus infection and T cells, NK
cells, and soluble immune mediators in elderly humans.
AB - We describe a cohort of 50 elderly subjects, age at least 70 years. We present
gender-specific findings in T lymphocyte markers and soluble immune mediators. We
show the correlation between cytomegalovirus infection status with CD56(dim) NK
cell responses to a variety of stimuli and with CD56(bright)/CD56(dim) NK cell
ratio. We also present the correlation of retinol binding protein (RBP)-4 plasma
levels with NK cell responses and we explore the relationship between gender and
adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56(dim) NK cell
responses. These data are discussed in Al-Attar et al. (2016) [1].
PMID- 27508214
TI - Large-scale gene expression profiling data of bone marrow stromal cells from
osteoarthritic donors.
AB - This data article contains data related to the research article entitled, "in
vitro characterization of bone marrow stromal cells from osteoarthritic donors"
[1]. Osteoarthritis (OA) represents the main indication for total joint
arthroplasty and is one of the most frequent degenerative joint disorders.
However, the exact etiology of OA remains unknown. Bone marrow stromal cells
(BMSCs) can be easily isolated from bone marrow aspirates and provide an
excellent source of progenitor cells. The data shows the identification of
pivotal genes and pathways involved in osteoarthritis by comparing gene
expression patterns of BMSCs from osteoarthritic versus healthy donors using an
array-based approach.
PMID- 27508215
TI - Phylodynamic analysis of porcine circovirus type 2: Methodological approach and
datasets.
AB - Since its first description, PCV2 has emerged as one of the most economically
relevant diseases for the swine industry. Despite the introduction of vaccines
effective in controlling clinical syndromes, PCV2 spread was not prevented and
some potential evidences of vaccine immuno escape have recently been reported
("Complete genome sequence of a novel porcine circovirus type 2b variant present
in cases of vaccine failures in the United States" (Xiao and Halbur, 2012) [1],
"Genetic and antigenic characterization of a newly emerging porcine circovirus
type 2b mutant first isolated in cases of vaccine failure in Korea" (Seo et al.,
2014) [2]). In this article, we used a collection of PCV2 full genomes, provided
in the present manuscript, and several phylogentic, phylodynamic and
bioinformatic methods to investigate different aspects of PCV2 epidemiology,
history and evolution (more thoroughly described in "PHYLODYNAMIC ANALYSIS of
PORCINE CIRCOVIRUS TYPE 2 REVEALS GLOBAL WAVES of EMERGING GENOTYPES and the
CIRCULATION of RECOMBINANT FORMS"[3]). The methodological approaches used to
consistently detect recombiantion events and estimate population dymanics and
spreading patterns of rapidly evolving ssDNA viruses are herein reported.
Programs used are described and original scripts have been provided. Ensembled
databases used are also made available. These consist of a broad collection of
complete genome sequences (i.e. 843 sequences; 63 complete genomes of PCV2a, 310
of PCV2b, 4 of PCV2c, 217 of PCV2d, 64 of CRF01, 140 of CRF02 and 45 of CRF03.),
divided in differnt ORF (i.e. ORF1, ORF2 and intergenic regions), of PCV2
genotypes and major Circulating Recombinat Forms (CRF) properly annotated with
respective collection data and country. Globally, all of these data can be used
as a starting point for further studies and for classification purpose.
PMID- 27508216
TI - Clinical, neuropsychological, and pre-stimulus dorsomedial thalamic nucleus
electrophysiological data in deep brain stimulation patients.
AB - The data presented here comprise clinical, neuropsychological, and intrathalamic
electrophysiological data from 7 patients with pharmacoresistant focal epilepsy
and are related to the article "Pre-stimulus thalamic theta power predicts human
memory formation" C.M. Sweeney-Reed, T. Zaehle, J. Voges, F.C. Schmitt, L.
Buentjen, K. Kopitzki, et al. (2016) [1]. The patients participated in a memory
paradigm after receiving electrodes implanted in the DMTN due to the surgical
approach taken in electrode insertion for deep brain stimulation of the anterior
thalamic nucleus. Epilepsy duration and pre-operative neuropsychological tests
provide an indication of the profile of patients receiving intrathalamic
electrode implantation and the memory capabilities in such a patient group. The
electrophysiological data were recorded from the right DMTN preceding stimulus
presentation during intentional memory encoding. The patients viewed a series of
photographic scenes, which they judged as indoors or outdoors. The 900 ms epochs
prior to stimulus presentation were labeled as preceding successful or
unsuccessful subsequent memory formation according to a subsequent memory test
for the items. The difference between theta power preceding successful versus
unsuccessful subsequent memory formation is shown against time for each patient
individually.
PMID- 27508217
TI - NMR and computational data of two novel antimicrobial peptides.
AB - Here we report details on the design and conformational analysis of two novel
peptides showing antimicrobial properties, as reported in the research article,
"New antimicrobial peptides against foodborne pathogens: from in silico design to
experimental evidence" G. Palmieri, M. Balestrieri, Y.T.R. Proroga, L. Falcigno,
A. Facchiano, A. Riccio, F. Capuano, R. Marrone, G. Campanile, A. Anastasio
(2016) [1]. NMR data, such as chemical shifts in two different solvents as well
as aCH protons deviations from random coil values and NOE patterns, are shown
together with the statistics of structural calculations. Strategy and particulars
of molecular design are presented.
PMID- 27508218
TI - Human lung epithelial cell A549 proteome data after treatment with titanium
dioxide and carbon black.
AB - Here, we have described the dataset relevant to the A549 cellular proteome
changes after exposure to either titanium dioxide or carbon black particles as
compared to the non-exposed controls, "Proteomic changes in human lung epithelial
cells (A549) in response to carbon black and titanium dioxide exposures" (Vuong
et al., 2016) [1]. Detailed methodologies on the separation of cellular proteins
by 2D-GE and the subsequent mass spectrometry analyses using MALDI-TOF-TOF-MS are
documented. Particle exposure-specific protein expression changes were measured
via 2D-GE spot volume analysis. Protein identification was done by querying mass
spectrometry data against SwissProt and RefSeq protein databases using Mascot
search engine. Two-way ANOVA analysis data provided information on statistically
significant A549 protein expression changes associated with particle exposures.
PMID- 27508219
TI - Dataset of milk whey proteins of two indigenous greek goat breeds.
AB - Due to its rarity and unique biological traits, as well as its growing financial
value, milk of dairy Greek small ruminants is continuously attracting interest
from both the scientific community and industry. For the construction of the
present dataset, cutting-edge proteomics methodologies were employed, in order to
investigate and characterize, for the first time, the milk whey proteome from the
two indigenous Greek goat breeds, Capra prisca and Skopelos. In total 822 protein
groups were identified in milk whey of the two breeds, The present data are
further discussed in the research article "Milk of Greek sheep and goat breeds;
characterization by means of proteomics" [1].
PMID- 27508220
TI - The dataset of proteins specifically interacted with activated TICAM-1.
AB - The presented data are related with our paper entitled "14-3-3-zeta participates
in TLR3-mediated TICAM-1 signal-platform formation" (Funami et al., 2016) [1].
These data show the proteins which specifically bind to the activated
(oligomerized) TICAM-1. Fifty-three proteins were identified as specifically
interacted with oligomerized TICAM-1. Mutant TICAM-1 cannot form the active
oligomer, so the proteins interacted with mutant TICAM-1 are dispensable for
TICAM-1-signaling. Among 53 proteins, 14-3-3-zeta specifically interacts with
oligomerized TICAM-1 to corroborate TICAM-1 signalosome.
PMID- 27508221
TI - Dataset of cocoa aspartic protease cleavage sites.
AB - The data provide information in support of the research article, "The cleavage
specificity of the aspartic protease of cocoa beans involved in the generation of
the cocoa-specific aroma precursors" (Janek et al., 2016) [1]. Three different
protein substrates were partially digested with the aspartic protease isolated
from cocoa beans and commercial pepsin, respectively. The obtained peptide
fragments were analyzed by matrix-assisted laser-desorption/ionization time-of
flight mass spectrometry (MALDI-TOF/TOF-MS/MS) and identified using the MASCOT
server. The N- and C-terminal ends of the peptide fragments were used to identify
the corresponding in-vitro cleavage sites by comparison with the amino acid
sequences of the substrate proteins. The same procedure was applied to identify
the cleavage sites used by the cocoa aspartic protease during cocoa fermentation
starting from the published amino acid sequences of oligopeptides isolated from
fermented cocoa beans.
PMID- 27508222
TI - Data on green Spanish-style Manzanilla table olives fermented in salt mixtures.
AB - This article contains processed data related to the research published in
"Fermentation in nutrient salt mixtures affects green Spanish-style Manzanilla
table olives" [1]. It displays information on the salt substitution by other
nutrient salts (potassium chloride and calcium chloride) during fermentation of
green Spanish-style Manzanilla table olives to produce healthier products.
Particularly, it studies the relationship between the different colour parameters
(L*, a*, b* and C i), firmness, and sensory attributes (saltiness, bitterness,
hardness, and fibrousness), and the composition of the initial brine in NaCl,
KCl, and CaCl2. The composition of the brines affected the characteristics of the
product. In general, the higher was the proportion of CaCl2 in the initial brines
the better was the colour. Also, the presence of this salt mitigated the
saltiness perception but increment those of bitterness, hardness, fibrousness,
and crunchiness. Besides, most of the sensory attribute scores could successfully
be predicted as a function of the Na, K, and Ca concentrations in the fermented
olive flesh. The work allows the production of table olives with specific
characteristics and predetermined mineral nutrient composition.
PMID- 27508223
TI - Data regarding association between serum osteoprotegerin level, numerous of
circulating endothelial-derived and mononuclear-derived progenitor cells in
patients with metabolic syndrome.
AB - Metabolic syndrome (MetS) is defined as cluster of multiple metabolic and
cardiovascular (CV) abnormalities included abdominal obesity, high-normal blood
pressure, dyslipidaemia, and impaired fasting glucose tolerance that exhibits has
a growing prevalence worldwide. We investigated whether an elevated level of
osteoprotegerin (OPG) predicts imbalance between different phenotypes of
circulating endothelial (EPCs) and mononuclear (MPCs) progenitor cells in MetS
patients. We have analyzed data regarding dysmetabolic disorder subjects without
known CV disease), as well as with known type two diabetes mellitus. All patients
have given their informed written consent for participation in the study. This
article contains data on the independent predictors of depletion in numerous of
circulating EPCs and MPCs in MetS patients. The data are supplemental to our
original research article describing detailed associations of elevated OPG level
in MetS patients with numerous of EPCs and MPCs beyond traditional CV risk
factors.
PMID- 27508224
TI - Dataset for an analysis of tourism and economic growth: A study of Sri Lanka.
AB - We use the sample from 1978 to 2014 for the paper
(doi:10.1016/j.tmp.2016.05.005). The data on GDP at constant 2005 USD (US
dollar), and the gross fixed capital formation at constant 2005 USD are extracted
from the World Bank (2015). The labour stock which includes direct and indirect
employment and the tourism receipts (in USD) are sourced from the Sri Lanka
Tourism Development Authority (http://www.sltda.lk/statistics). Tourism receipts
as a per cent of GDP is used to measure tourism demand. The capital stock data is
computed using perpetual inventory method, where a depreciation rate of 8 per
cent is assumed with the initial capital stock as 1.05 times the GDP of 1969 at
constant 2005 USD. The output per worker and capital per worker is computed by
dividing the GDP and capital stock by the labour stock, respectively.
PMID- 27508225
TI - Data supporting functional diversity of the marine bacterium Cobetia amphilecti
KMM 296.
AB - Data is presented in support of functionality of hyper-diverse protein families
encoded by the Cobetia amphilecti KMM 296 (formerly Cobetia marina KMM 296)
genome ("The genome of the marine bacterium Cobetia marina KMM 296 isolated from
the mussel Crenomytilus grayanus (Dunker, 1853)" [1]) providing its nutritional
versatility, adaptability and biocontrol that could be the basis of the marine
bacterium evolutionary and application potential. Presented data include the
information of growth and biofilm-forming properties of the food-associated
isolates of Pseudomonas, Bacillus, Listeria, Salmonella and Staphylococcus under
the conditions of their co-culturing with C. amphilecti KMM 296 to confirm its
high inter-species communication and anti-microbial activity. Also included are
the experiments on the crude petroleum consumption by C. amphilecti KMM 296 as
the sole source of carbon in the presence of sulfate or nitrate to ensure its
bioremediation capacity. The multifunctional C. amphilecti KMM 296 genome is a
promising source for the beneficial psychrophilic enzymes and essential secondary
metabolites.
PMID- 27508226
TI - Data for the co-expression and purification of human recombinant CaMKK2 in
complex with calmodulin in Escherichia coli.
AB - Calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) has been implicated in a
range of conditions and pathologies from prostate to hepatic cancer. Here, we
describe the expression in Escherichia coli and the purification protocol for the
following constructs: full-length CaMKK2 in complex with CaM, CaMKK2 'apo',
CaMKK2 (165-501) in complex with CaM, and the CaMKK2 F267G mutant. The protocols
described have been optimized for maximum yield and purity with minimal
purification steps required and the proteins subsequently used to develop a
fluorescence-based assay for drug binding to the kinase, "Using the fluorescent
properties of STO-609 as a tool to assist structure-function analyses of
recombinant CaMKK2" [1].
PMID- 27508227
TI - Data on characterizing the gene expression patterns of neuronal ceroid
lipofuscinosis genes: CLN1, CLN2, CLN3, CLN5 and their association to interneuron
and neurotransmission markers: Parvalbumin and Somatostatin.
AB - The article contains raw and analyzed data related to the research article
"Neuronal ceroid lipofuscinosis genes, CLN2, CLN3, CLN5 are spatially and
temporally co-expressed in a developing mouse brain" (Fabritius et al., 2014)
[1]. The processed data gives an understanding of the development of the cell
types that are mostly affected by defective function of CLN proteins, timing of
expression of CLN1, CLN2, CLN3 and CLN5 genes in a murine model. The data shows
relationship between the expression pattern of these genes during neural
development. Immunohistochemistry was used to identify known interneuronal
markers for neurotransmission and cell proliferation: parvalbumin, somatostatin
subpopulations of interneurons. Non-radioactive in-situ hybridization detected
CLN5 mRNA in the hippocampus. Throughout the development strong expression of CLN
genes were identified in the germinal epithelium and in ventricle regions,
cortex, hippocampus, and cerebellum. This provides supportive evidence that CLN1,
CLN2, CLN3 and CLN5 genes may be involved in synaptic pruning.
PMID- 27508228
TI - Data of fluorescence, UV-vis absorption and FTIR spectra for the study of
interaction between two food colourants and BSA.
AB - In this data article, the fluorescence, UV-vis absorption and FTIR spectra data
of BSA-AR1/AG50 system were presented, which were used for obtaining the binding
characterization (such as binding constant, binding distance, binding site,
thermodynamics, and structural stability of protein) between BSA and AR1/AG50.
PMID- 27508229
TI - Proteomic dataset of Paracentrotus lividus gonads of different sexes and at
different maturation stages.
AB - We report the proteomic dataset of gonads from wild Paracentrotus lividus related
to the research article entitled "Proteomic changes occurring along gonad
maturation in the edible sea urchin Paracentrotus lividus" [1]. Gonads of three
individuals per sex in the recovery, pre-mature, mature, and spent stages were
analyzed using a shotgun proteomics approach based on filter-aided sample
preparation followed by tandem mass spectrometry, protein identification carried
out using Sequest-HT as the search engine within the Proteome Discoverer
informatics platform, and label-free differential analysis. The dataset has been
deposited in the ProteomeXchange Consortium via the PRIDE partner repository with
the dataset identifier PRIDE: PXD004200.
PMID- 27508230
TI - Time-course gene expression data on the transcriptional effects of Aminaphtone on
ECV304 endothelial cells.
AB - We previously showed that Aminaphtone, a drug used in the treatment of chronic
venous insufficiency, modulates several vasoactive factors, such as endothelin-1
and adhesion molecules. Here, we provide data of time-course experiments about
the effects of Aminaphtone on gene expression at the genome-wide level in human
endothelial cells undergoing cytokine stimulation in vitro. ECV-304 endothelial
cells were incubated with interleukin-1beta (IL-1beta) in the presence or absence
of Aminaphtone for 1, 3, and 6 h. Gene expression profiles were analyzed by
microarray. This article contains complete data on the genes significantly
modulated by the drug over time. The data are supplemental to our original
research article reporting detailed analysis of the actions of Aminaphtone on IL
1beta stimulated endothelial cells at the molecular level, "Gene expression
profiling reveals novel protective effects of Aminaphtone on ECV304 endothelial
cells" (Salazar et al., 2016) [1].
PMID- 27508231
TI - Datasets of genes coexpressed with FBN1 in mouse adipose tissue and during human
adipogenesis.
AB - This article contains data related to the research article entitled "Expression
of FBN1 during adipogenesis: relevance to the lipodystrophy phenotype in Marfan
syndrome and related conditions" [1]. The article concerns the expression of
FBN1, the gene encoding the extracellular matrix protein fibrillin-1, during
adipogenesis in vitro and in relation to adipose tissue in vivo. The encoded
protein has recently been shown to produce a short glucogenic peptide hormone,
(Romere et al., 2016) [2], and this gene is therefore a key gene for regulating
blood glucose levels. FBN1 and coexpressed genes were examined in mouse strains
and in human cells undergoing adipogenesis. The data show the genes that were
coexpressed with FBN1, including genes coding for other connective tissue
proteins and the proteases that modify them and for the transcription factors
that control their expression. Data analysed were derived from datasets available
in the public domain and the analysis highlights the utility of such datasets for
ongoing analysis and hence reduction in the use of experimental animals.
PMID- 27508232
TI - Real-world datasets for portfolio selection and solutions of some stochastic
dominance portfolio models.
AB - A large number of portfolio selection models have appeared in the literature
since the pioneering work of Markowitz. However, even when computational and
empirical results are described, they are often hard to replicate and compare due
to the unavailability of the datasets used in the experiments. We provide here
several datasets for portfolio selection generated using real-world price values
from several major stock markets. The datasets contain weekly return values,
adjusted for dividends and for stock splits, which are cleaned from errors as
much as possible. The datasets are available in different formats, and can be
used as benchmarks for testing the performances of portfolio selection models and
for comparing the efficiency of the algorithms used to solve them. We also
provide, for these datasets, the portfolios obtained by several selection
strategies based on Stochastic Dominance models (see "On Exact and Approximate
Stochastic Dominance Strategies for Portfolio Selection" (Bruni et al. [2])). We
believe that testing portfolio models on publicly available datasets greatly
simplifies the comparison of the different portfolio selection strategies.
PMID- 27508233
TI - Data on optimized production and characterization of alkaline proteases from
newly isolated alkaliphiles from Lonar soda lake, India.
AB - Alkaline proteases are one of the industrially important enzymes and generally
preferred from alkaliphilic sources. Here we have provided the data on optimized
production and characterization of alkaline proteases from five newly isolated
and identified alkaliphiles from Lonar soda lake, India. The data provided for
optimization of physicochemical parameters for maximum alkaline proteases
production is based on OVAT (one variable at a time) approach. Alkaline protease
production (U/mL) recorded by using different agro industrial residues is
included in the given data. Further readers can find more information in our
previously published research article where we have already described about the
methods used and comparative analysis of the data recorded regarding optimized
production, characterization and application of alkaline proteases isolated from
Lonar soda lake isolates (http://dx.doi.org/10.1016/j.bcab.2016.06.002) [1]. The
data provided here by us is useful to other researchers for setting up various
suitable statistical models to perform optimization studies other than OVAT
approach.
PMID- 27508234
TI - Data on daily fluoride intake based on drinking water consumption prepared by
household desalinators working by reverse osmosis process.
AB - In this data article, we evaluated the daily fluoride contents in 20 household
desalinators working by reverse osmosis (RO) process in Bushehr, Iran. The
concentration levels of fluoride in inlet and outlet waters were determined by
the standard SPADNS method using a spectrophotometer (M501 Single Beam Scanning
UV/VIS, UK). The fluoride content in outlet waters were compared with EPA and WHO
guidelines for drinking water.
PMID- 27508235
TI - Data on the verification and validation of segmentation and registration methods
for diffusion MRI.
AB - The verification and validation of segmentation and registration methods is a
necessary assessment in the development of new processing methods. However,
verification and validation of diffusion MRI (dMRI) processing methods is
challenging for the lack of gold-standard data. The data described here are
related to the research article entitled "Surface-driven registration method for
the structure-informed segmentation of diffusion MR images" [1], in which
publicly available data are used to derive golden-standard reference-data to
validate and evaluate segmentation and registration methods in dMRI.
PMID- 27508236
TI - Dataset of milk whey proteins of three indigenous Greek sheep breeds.
AB - The importance and unique biological traits, as well as the growing financial
value, of milk from small Greek ruminants is continuously attracting interest
from both the scientific community and industry. In this regard the construction
of a reference dataset of the milk of the Greek sheep breeds is of great
interest. In order to obtain such a dataset we employed cutting-edge proteomics
methodologies to investigate and characterize, the proteome of milk from the
three indigenous Greek sheep breeds Mpoutsko, Karagouniko and Chios. In total,
more than 1300 protein groups were identified in milk whey from these breeds,
reporting for the first time the most detailed proteome dataset of this precious
biological material. The present results are further discussed in the research
paper "Milk of Greek sheep and goat breeds; characterization by means of
proteomics" (Anagnostopoulos et al. 2016) [1].
PMID- 27508237
TI - Bacterial clinical infectious diseases ontology (BCIDO) dataset.
AB - This article describes the Bacterial Infectious Diseases Ontology (BCIDO) dataset
related to research published in http:dx.doi.org/ 10.1016/j.jbi.2015.07.014 [1],
and contains the Protege OWL files required to run BCIDO in the Protege
environment. BCIDO contains 1719 classes and 39 object properties.
PMID- 27508238
TI - Data from thermal testing of the Open Source Cryostage.
AB - The data presented here is related to the research article "An open source
cryostage and software analysis method for detection of antifreeze activity"
(Buch and Ramlov, 2016) [1]. The design of the Open Source Cryostage (OSC) is
tested in terms of thermal limits, thermal efficiency and electrical efficiency.
This article furthermore includes an overview of the electrical circuitry and a
flowchart of the software program controlling the temperature of the OSC. The
thermal efficiency data is presented here as degrees per volt and maximum cooling
capacity.
PMID- 27508239
TI - Data for behavioral results and brain regions showing a time effect during pair
association retrieval.
AB - The current data article provides behavioral and neuroimaging data for the
research article "Relatedness-dependent rapid development of brain activity in
anterior temporal cortex during pair-association retrieval" (Jimura et al., 2016)
[1]. Behavioral performance is provided in a table. Fig. 2 of the article is
based on this table. Brain regions showing time effect are provided in a table. A
statistical activation map for the time effect is shown in Fig. 3C of the
article.
PMID- 27508240
TI - Data on affected cancer-related genes in pediatric t(12;21)-positive acute
lymphoblastic leukemia patients harboring unbalanced der(6)t(X;6) translocations.
AB - The t(12;21)(p13;q22), leading to ETV6/RUNX1 fusion, is of importance for
leukemogenesis in acute lymphoblastic leukemia but is not sufficient for the
leukemic transformation. Acquired secondary chromosomal aberrations are necessary
for overt leukemia but their complete nature and genes involved are still
elusive. In our recent publication, "Oligo-based aCGH analysis reveals cryptic
unbalanced der(6)t(X;6) in pediatric t(12;21)-positive acute lymphoblastic
leukemia", we identified acquired common concurrent regions with 6q deletion and
Xq duplication E. Kjeldsen (2016) [1]. The present article provides data on genes
that are associated with hematological malignancy and other cancers located in
these common regions of chromosomal aberrations.
PMID- 27508241
TI - Data set demonstrating an absence of touch effects on social orienting in adults.
AB - Forty-five women participated in a variant of the social orienting paradigm
employed in "Maternal Touch Predicts Attentional Bias Towards Faces in Young
Children" (Reece, in press) [1]. On a given trial, they saw a mathematical
equation and indicated whether this equation was true or false. Equations were
superimposed on face or house distractors. A female experimenter sat next to the
participant. In separate blocks, she either rested her hand on the participants
arm or refrained from touching. Performance was poorer on trials with face than
house distractors. However, experimenter touch failed to modulate this effect.
Here we present raw and analyzed data of this companion experiment.
PMID- 27508242
TI - Data for default network reduced functional connectivity in meditators,
negatively correlated with meditation expertise.
AB - FMRI data described here was recorded during resting-state in Mindfulness
Meditators (MM) and control participants (see "Task-induced activity and resting
state fluctuations undergo similar alterations in visual and DMN areas of long
term meditators" Berkovich-Ohana et al. (2016) [1] for details). MM participants
were also scanned during meditation. Analyses focused on functional connectivity
within and between the default mode network (DMN) and visual network (Vis). Here
we show data demonstrating that: 1) Functional connectivity within the DMN and
the Visual networks were higher in the control group than in the meditators; 2)
Data show an increase for the functional connectivity between the DMN and the
Visual networks in the meditators compared to controls; 3) Data demonstrate that
functional connectivity both within and between networks reduces during
meditation, compared to the resting-state; and 4) A significant negative
correlation was found between DMN functional connectivity and meditation
expertise. The reader is referred to Berkovich-Ohana et al. (2016) [1] for
further interpretation and discussion.
PMID- 27508243
TI - Dataset and standard operating procedure for newborn screening of six lysosomal
storage diseases: By tandem mass spectrometry.
AB - In this data article we provide a detailed standard operating procedure for
performing a tandem mass spectrometry, multiplex assay of 6 lysosomal enzymes for
newborn screening of the lysosomal storage diseases Mucopolysaccharidosis-I,
Pompe, Fabry, Niemann-Pick-A/B, Gaucher, and Krabbe, (Elliott, et al., 2016) [1].
We also provide the mass spectrometry peak areas for the product and internal
standard ions typically observed with a dried blood spot punch from a random
newborn, and we provide the daily variation of the daily mean activities for all
6 enzymes.
PMID- 27508244
TI - Data in support for the measurement of serum 25-hydroxyvitamin D (25OHD) by
tandem mass spectrometry.
AB - This article provides data and a method related to a research paper entitled
"Assessing vitamin D nutritional status: is capillary blood adequate?" (Jensen et
al., 2016) [1]. Circulating 25OHD, the accepted biomarker of the vitamin D
nutritional status, is routinely measured by automated immunoassays, that
although may be performed in hospital central laboratories, often suffer from a
lack of specificity with regards to the different vitamin D metabolites,
"Measurement of circulating 25-hydroxyvitamin D: a historical review" (Le Goff et
al., 2015) [2]. Mass spectrometry offers this specificity. This article describes
the performance of an in-house tandem mass spectrometry method for the individual
measurement of 25OHD3, 25OHD2 and 3-epi-25OHD3.
PMID- 27508245
TI - Vehicular crash data used to rank intersections by injury crash frequency and
severity.
AB - This article contains data on research conducted in "A double standard model for
allocating limited emergency medical service vehicle resources ensuring service
reliability" (Liu et al., 2016) [1]. The crash counts were sorted out from
comprehensive crash records of over one thousand major signalized intersections
in the city of Chicago from 2004 to 2010. For each intersection, vehicular
crashes were counted by crash severity levels, including fatal, injury Types A,
B, and C for major, moderate, and minor injury levels, property damage only
(PDO), and unknown. The crash data was further used to rank intersections by
equivalent injury crash frequency. The top 200 intersections with the highest
number of crash occurrences identified based on crash frequency- and severity
based scenarios are shared in this brief. The provided data would be a valuable
source for research in urban traffic safety analysis and could also be utilized
to examine the effectiveness of traffic safety improvement planning and
programming, intersection design enhancement, incident and emergency management,
and law enforcement strategies.
PMID- 27508246
TI - Summary of high field diffusion MRI and microscopy data demonstrate
microstructural aberration in chronic mild stress rat brain.
AB - This data article describes a large, high resolution diffusion MRI data set from
fixed rat brain acquired at high field strength. The rat brain samples consist of
21 adult rat brain hemispheres from animals exposed to chronic mild stress
(anhedonic and resilient) and controls. Histology from amygdala of the same brain
hemispheres is also included with three different stains: DiI and Hoechst stained
microscopic images (confocal microscopy) and ALDH1L1 antibody based
immunohistochemistry. These stains may be used to evaluate neurite density (DiI),
nuclear density (Hoechst) and astrocytic density (ALDH1L1). This combination of
high field diffusion data and high resolution images from microscopy enables
comparison of microstructural parameters derived from diffusion MRI to
histological microstructure. The data provided here is used in the article
(Jespersen, 2016) [1].
PMID- 27508247
TI - 16S rRNA amplicon sequencing dataset for conventionalized and conventionally
raised zebrafish larvae.
AB - Data presented here contains metagenomic analysis regarding the sequential
conventionalization of germ-free zebrafish embryos. Zebrafish embryos that
underwent a germ-free sterilization process immediately after fertilization were
promptly exposed to and raised to larval stage in conventional fish water. At 6
days postfertilization (dpf), these "conventionalized" larvae were compared to
zebrafish larvae that were raised in conventional fish water never undergoing the
initial sterilization process. Bacterial 16S rRNA amplicon sequencing was
performed on DNA isolated from homogenates of the larvae revealing distinct
microbiota variations between the two groups. The dataset described here is also
related to the research article entitled "Microbial modulation of behavior and
stress responses in zebrafish larvae" (Davis et al., 2016) [1].
PMID- 27508248
TI - Data on alteration of hormone and growth factor receptor profiles over
progressive passages of breast cancer cell lines representing different clinical
subtypes.
AB - Human breast cancers are a highly heterogeneous group of tumours consisting of
several molecular subtypes with a variable profile of hormone, growth factor
receptors and cytokeratins [1]. Here, the data shows immunofluorescence profiling
of four different cell lines belonging to distinct clinical subtypes of breast
cancer. Post revival, the cell lines were passaged in culture and
immunophenotyping was done for ER, HER-2, AR and EGFR. Data for the markers from
early passage (5th) through passages as late as 25 for the different cell lines
is presented.
PMID- 27508250
TI - Data of the natural and pharmaceutical angiotensin-converting enzyme inhibitor
isoleucine-tryptophan as a potent blocker of matrix metalloproteinase-2
expression in rat aorta.
AB - The present data are related to the research article entitled "Whey peptide
isoleucine-tryptophan inhibits expression and activity of matrix
metalloproteinase-2 in rat aorta" [1]. Here we present data on removal of
endothelium from aorta, endothelium dependent aortic relaxation and inhibition of
expression of pro-MMP2 by di-peptide isoleucine-tryptophan (IW). Experiments were
performed in rat aortic endothelial cells (EC) and smooth muscle cells (SMC) in
vitro, along with isolated rat aorta ex vivo. The cells and isolated aorta were
stimulated with angiotensin II (ANGII) or angiotensin I (ANGI). ACE activity was
inhibited by treatment with either IW or captopril (CA). Losartan was used as a
blocker of angiotensin type-1 receptor. IW inhibited MMP2 protein expression
induced with ANGI in a dose-dependent manner. IW was effective both in ECs and
SMCs, as well as in isolated aorta. Similarly, captopril (CA) inhibited ANGI
induced MMP2 protein expression in both in vitro and ex vivo. Neither IW nor CA
inhibited ANGII-induced MMP2 protein expression in contrast to losartan. The data
also displays that removal of endothelium in isolated rat aorta abolished the
endothelium-dependent relaxation induced with acetylcholine. However, SMC
dependent relaxation induced with sodium nitroprusside remained intact. Finally,
the data provides histological evidence of selective removal of endothelial cells
from aorta.
PMID- 27508251
TI - Data on metal contents (As, Ag, Sr, Sn, Sb, and Mo) in sediments and shells of
Trachycardium lacunosum in the northern part of the Persian Gulf.
AB - In this data article, by using inductively coupled plasma optical spectrometry
(ICP-OES), we aimed to (1) determine the concentration levels of As, Ag, Sr, Sn,
Sb, and Mo in the sediments and the shells of Trachycardium lacunosum
simultaneously in two separated areas (unpolluted and polluted areas) (2)
comparison between the metal contents of sediments in the unpolluted and polluted
areas as well as shells. Analysis of data showed that sediment as well as shell
samples in polluted area contained significantly higher concentration levels of
all measured metals compared with unpolluted area.
PMID- 27508249
TI - Data on publications, structural analyses, and queries used to build and utilize
the AlloRep database.
AB - The AlloRep database (www.AlloRep.org) (Sousa et al., 2016) [1] compiles
extensive sequence, mutagenesis, and structural information for the LacI/GalR
family of transcription regulators. Sequence alignments are presented for >3000
proteins in 45 paralog subfamilies and as a subsampled alignment of the whole
family. Phenotypic and biochemical data on almost 6000 mutants have been compiled
from an exhaustive search of the literature; citations for these data are
included herein. These data include information about oligomerization state,
stability, DNA binding and allosteric regulation. Protein structural data for 65
proteins are presented as easily-accessible, residue-contact networks. Finally,
this article includes example queries to enable the use of the AlloRep database.
See the related article, "AlloRep: a repository of sequence, structural and
mutagenesis data for the LacI/GalR transcription regulators" (Sousa et al., 2016)
[1].
PMID- 27508252
TI - Benchmark dataset for undirected and Mixed Capacitated Arc Routing Problems under
Time restrictions with Intermediate Facilities.
AB - In this article we present benchmark datasets for the Mixed Capacitated Arc
Routing Problem under Time restrictions with Intermediate Facilities (MCARPTIF).
The problem is a generalisation of the Capacitated Arc Routing Problem (CARP),
and closely represents waste collection routing. Four different test sets are
presented, each consisting of multiple instance files, and which can be used to
benchmark different solution approaches for the MCARPTIF. An in-depth description
of the datasets can be found in "Constructive heuristics for the Mixed Capacity
Arc Routing Problem under Time Restrictions with Intermediate Facilities"
(Willemseand Joubert, 2016) [2] and "Splitting procedures for the Mixed
Capacitated Arc Routing Problem under Time restrictions with Intermediate
Facilities" (Willemseand Joubert, in press) [4]. The datasets are publicly
available from "Library of benchmark test sets for variants of the Capacitated
Arc Routing Problem under Time restrictions with Intermediate Facilities"
(Willemse and Joubert, 2016) [3].
PMID- 27508253
TI - Data on NAEP 2011 writing assessment prior computer use.
AB - This data article contains information based on the 2011 National Assessment of
Educational Progress in Writing Restricted-Use Data, available from the National
Center for Education Statistics (NCES Pub. No. 2014476).
https://nces.ed.gov/nationsreportcard/researchcenter/datatools.aspx. The data
include the statistical relationships between survey reports of teachers and
students regarding prior use of computers and other technology and writing
achievement levels on the 2011 computer-based NAEP writing assessment. This data
article accompanies "The Effects of Prior Computer Use on Computer-Based Writing:
The 2011 NAEP Writing Assessment" [1].
PMID- 27508254
TI - Myelin contrast across lamina at 7T, ex-vivo and in-vivo dataset.
AB - In this article we report the complete data obtained in-vivo for the paper:
"Lines of Baillarger in vivo and ex-vivo: myelin contrast across lamina at 7T MRI
and histology" (Fracasso et al., 2015) [1]. Single participant data (4
participants) from the occipital lobe acquisition are reported for axial, coronal
and sagittal slices; early visual area functional localization and laminar
profiles are reported. Data from whole brain images are reported and described (5
participants), for axial, coronal and sagittal slices. Laminar profiles from
occipital, parietal and frontal lobes are reported. The data reported in this
manuscript complements the paper (Fracasso et al., 2015) [1] by providing the
full set of results from the complete pool of participants, on a single
participant basis. Moreover, we provide histological images from the ex-vivo
sample reported in Fracasso et al. (2015) [1].
PMID- 27508255
TI - A semi-simulated EEG/EOG dataset for the comparison of EOG artifact rejection
techniques.
AB - Artifact rejection techniques are used to recover the brain signals underlying
artifactual electroencephalographic (EEG) segments. Although over the last few
years many different artifact rejection techniques have been proposed
(http://dx.doi.org/10.1109/JSEN.2011.2115236[1],
http://dx.doi.org/10.1016/j.clinph.2006.09.003[2],
http://dx.doi.org/10.3390/e16126553[3]), none has been established as a gold
standard so far, because assessing their performance is difficult and subjective
(http://dx.doi.org/10.1109/ITAB.2009.5394295[4],
http://dx.doi.org/10.1016/j.bspc.2011.02.001[5], http://dx.doi.org/10.1007/978-3
540-89208-3_300. [6]). This limitation is mainly based on the fact that the
underlying artifact-free brain signal is unknown, so there is no objective way to
measure how close the retrieved signal is to the real one. This article solves
the aforementioned problem by presenting a semi-simulated EEG dataset, where
artifact-free EEG signals are manually contaminated with ocular artifacts, using
a realistic head model. The significant part of this dataset is that it contains
the pre-contamination EEG signals, so the brain signals underlying the EOG
artifacts are known and thus the performance of every artifact rejection
technique can be objectively assessed.
PMID- 27508256
TI - Input data for inferring species distributions in Kyphosidae world-wide.
AB - Input data files for inferring the relationship among the family Kyphosidae, as
presented in (Knudsen and Clements, 2016) [1], is here provided together with
resulting topologies, to allow the reader to explore the topologies in detail.
The input data files comprise seven nexus-files with sequence alignments of mtDNA
and nDNA markers for performing Bayesian analysis. A matrix of recoded character
states inferred from the morphology examined in museum specimens representing
Dichistiidae, Girellidae, Kyphosidae, Microcanthidae and Scorpididae, is also
provided, and can be used for performing a parsimonious analysis to infer the
relationship among these perciform families. The nucleotide input data files
comprise both multiple and single representatives of the various species to allow
for inference of the relationship among the species in Kyphosidae and between the
families closely related to Kyphosidae. The '.xml'-files with various constrained
relationships among the families potentially closely related to Kyphosidae are
also provided to allow the reader to rerun and explore the results from the
stepping-stone analysis. The resulting topologies are supplied in newick-file
formats together with input data files for Bayesian analysis, together with
'.xml'-files. Re-running the input data files in the appropriate software, will
enable the reader to examine log-files and tree-files themselves.
PMID- 27508257
TI - Data on cell growth inhibition induced by anti-VEGF siRNA delivered by Stealth
liposomes incorporating G2 PAMAM-cholesterol versus Metafectene(r) as a function
of exposure time and siRNA concentration.
AB - In this data article, carboxyfluorescein-loaded liposomes were prepared and
purified from free carboxyfluorescein using gel filtration chromatography in the
first part. In the next part, following preparation of anti-VEGF siRNA loaded
liposomes incorporating hydrophobically modified G2 PAMAM dendrimer (G2-Chol40%)
(Golkar et al., 2016) [1], the cell growth inhibition induced by the formulations
(siRNA/Metafectene complexes and siRNA loaded liposomes incorporating hydrophobic
G2) was evaluated at two exposure times through MTT assay in a breast cancer cell
(SKBR-3) and compared by two-way ANOVA.
PMID- 27508258
TI - Single-leg landing neuromechanical data following load and land height
manipulations.
AB - Lower extremity sagittal kinematic and kinetic data are summarized alongside
electrical muscle activities during single-leg landing trials completed in
contrasting external load and landing height conditions. Nineteen subjects were
analyzed during 9 landing trials in each of 6 experimental conditions computed as
percentages of subject anthropometrics (bodyweight: BW and subject height: H; BW,
BW+12.5%, BW+25%, and H12.5%, H25%). Twelve lower extremity variables (sagittal
hip, knee, ankle angles and moments, vertical ground reaction force (GRFz),
gluteus maximus, biceps femoris, vastus medials, medial gastrocnemius, and
tibialis anterior muscles) were assessed using separate principal component
analyses (PCA). Variable trends across conditions were summarized in
"Neuromechanical synergies in single-leg landing reveal changes in movement
control. Human Movement Science" (Nordin and Dufek, 2016) [1], revealing changes
in landing biomechanics and movement control.
PMID- 27508259
TI - Data on biochemical fluxes generated from biofabricated enzyme complexes
assembled through engineered tags and microbial transglutaminase.
AB - Data presented is related to an article titled "Modular construction of multi
subunit protein complexes using engineered tags and microbial transglutaminase"
(Bhokisham et al., 2016) [1]. In this article, we have presented western blot and
flux data associated with assembly of Pfs-LuxS enzyme complexes on beads using
uni-tagged and bi-tagged LuxS enzymes. We have also presented biochemical flux
following changes in enzyme stoichiometries. We covalently coupled a Pfs-LuxS
complex with Protein G, an antibody binding non-enzyme component and directed
these complexes to the surfaces of bacterial cells via anti-Escherichia coli
antibodies. Fluorescence microscopy images represented the altered behavior of
bacterial cells in response to the autoinducer-2 that is synthesized by the
Protein G-enzyme complexes.
PMID- 27508260
TI - Data and programs in support of network analysis of genes and their association
with diseases.
AB - The network-based approaches that were employed in order to depict the
relationships between human genetic diseases and their associated genes are
described. Towards this direction, monopartite disease-disease and gene-gene
networks were constructed from bipartite gene-disease association networks. The
latter were created by collecting and integrating data from three diverse
resources, each one with different content, covering from rare monogenic
disorders to common complex diseases. Moreover, topological and clustering graph
analyses were performed. The methodology and the programs presented in this
article are related to the research article entitled "Network analysis of genes
and their association with diseases" [1].
PMID- 27508261
TI - Data on the optimization of a GC-MS procedure for the determination of total
plasma myo-inositol.
AB - Myo-inositol (MI) is one of the stereoisomers of hexahydroxycyclohexane, which
plays an important role in intracellular signal pathway. Derivatization is an
indispensable step in both external and internal standard method during the
chromatography-mass spectrometer (GC-MS) detection, as MI can't be ionized
directly. It is valuable to optimize the derivative process and the detection
volume for clinical detection. This article contains optimization data related to
research publication "Quantification of plasma myo-inositol using gas
chromatography-mass spectrometry" [1]. Here we introduce the data on the
optimized derivatization volume, temperature, duration and the detection volume.
PMID- 27508262
TI - Data on pro-inflammatory cytokines IL-1beta, IL-17, and IL-6 in the peripheral
blood of HIV-infected individuals.
AB - Our most recent data indicate differences in the levels of pro-inflammatory
cytokines (IL-1beta, IL-17, and IL-6) and malondialdehyde (MDA), a stable end
product of lipid peroxidation in the plasma samples between HIV positive
individuals with low CD4 T cell counts <200 mm(3) and HIV positive individuals
with CD4 T cell counts between 200 and 300 mm(3) (ee). The data lend support and
provide valuable correlation between CD4 T cell counts and the levels of
inflammatory cytokines in HIV positive individuals.
PMID- 27508263
TI - Metagenomic and near full-length 16S rRNA sequence data in support of the
phylogenetic analysis of the rumen bacterial community in steers.
AB - Amplicon sequencing utilizing next-generation platforms has significantly
transformed how research is conducted, specifically microbial ecology. However,
primer and sequencing platform biases can confound or change the way scientists
interpret these data. The Pacific Biosciences RSII instrument may also
preferentially load smaller fragments, which may also be a function of PCR
product exhaustion during sequencing. To further examine theses biases, data is
provided from 16S rRNA rumen community analyses. Specifically, data from the
relative phylum-level abundances for the ruminal bacterial community are provided
to determine between-sample variability. Direct sequencing of metagenomic DNA was
conducted to circumvent primer-associated biases in 16S rRNA reads and
rarefaction curves were generated to demonstrate adequate coverage of each
amplicon. PCR products were also subjected to reduced amplification and pooling
to reduce the likelihood of PCR product exhaustion during sequencing on the
Pacific Biosciences platform. The taxonomic profiles for the relative phylum
level and genus-level abundance of rumen microbiota as a function of PCR pooling
for sequencing on the Pacific Biosciences RSII platform were provided. For more
information, see "Evaluation of 16S rRNA amplicon sequencing using two next
generation sequencing technologies for phylogenetic analysis of the rumen
bacterial community in steers" P.R. Myer, M. Kim, H.C. Freetly, T.P.L. Smith
(2016) [1].
PMID- 27508264
TI - Hawai'i Coral Disease database (HICORDIS): species-specific coral health data
from across the Hawaiian archipelago.
AB - The Hawai'i Coral Disease database (HICORDIS) houses data on colony-level coral
health condition observed across the Hawaiian archipelago, providing information
to conduct future analyses on coral reef health in an era of changing
environmental conditions. Colonies were identified to the lowest taxonomic
classification possible (species or genera), measured and assessed for visual
signs of health condition. Data were recorded for 286,071 coral colonies surveyed
on 1819 transects at 660 sites between 2005 and 2015. The database contains
observations for 60 species from 22 genera with 21 different health conditions.
The goals of the HICORDIS database are to: i) provide open access, quality
controlled and validated coral health data assembled from disparate surveys
conducted across Hawai'i; ii) facilitate appropriate crediting of data; and iii)
encourage future analyses of coral reef health. In this article, we describe and
provide data from the HICORDIS database. The data presented in this paper were
used in the research article "Satellite SST-based Coral Disease Outbreak
Predictions for the Hawaiian Archipelago" (Caldwell et al., 2016) [1].
PMID- 27508265
TI - Data on the descriptive overview and the quality assessment details of 12
qualitative research papers.
AB - This data article presents the supplementary material for the review paper "Role
of acceptability barriers in delayed diagnosis of Tuberculosis: Literature review
from high burden countries" (Barnabishvili et al., in press) [1]. General
overview of 12 qualitative papers, including the details about authors, years of
publication, data source locations, study objectives, overview of methods, study
population characteristics, as well as the details of intervention and the
outcome parameters of the papers are summarized in the first two tables included
to the article. Quality assessment process of the methodological strength of 12
papers and the results of the critical appraisal are further described and
summarized in the second part of the article.
PMID- 27508266
TI - Human leukocyte antigen (HLA)-binding epitopes dataset for the newly identified T
cell antigens of Mycobacterium immunogenum.
AB - The dataset described herein is related to our article entitled "T-cell antigens
of Mycobacterium immunogenum (MI), an etiological agent of occupational
hypersensitivity pneumonitis'' (Chandra and Yadav, 2016) [1]. The data include in
silico-predicted T-cell epitopes of the T-cell antigens AgA and AgD of MI
predicted to bind to HLA-I or HLA-II alleles. Data on two reference T-cell
antigens ESAT-6 and CFP-10 of Mycobacterium tuberculosis H37Rv are included for
comparison. The data for each antigen include the predicted epitope's amino acid
sequence, its first amino acid position, and its ability to bind HLA-I or HLA-II
allele(s).
PMID- 27508267
TI - CZTS x Se1-x nanocrystals: Composition dependent method of preparation,
morphological characterization and cyclic voltammetry data analysis.
AB - In this article, synthesis procedures of preparation of copper zinc tin sulpho
selenide (CZTS x Se1-x ) alloy nanocrystals and the data acquired for the
material characterization are presented. This data article is related to the
research article doi: http://dx.doi.org/10.1016/j.solmat.2016.06.030 (Jadhav et
al., 2016) [1]. FTIR data have been presented which helped in confirmation of
adsorption of oleylamine on CZTS x Se1-x . Transmission electron microscopy
(TEM), Field emission scanning electron microscopy (FESEM) and atomic force
microscopy (AFM) data have been presented which have been used to reveal the
morphological details of the nanocrystals. The Energy dispersive X-ray analysis
(EDAX) based elemental mapping data has been presented to confirm the elemental
composition of nanocrystals. Procedure for the preparation of CZTS x Se1-x based
working electrode for the CV measurements have been given. The summary table for
the optical, electrochemical band gaps, valance and conduction band edges as a
function of composition are listed for the ready reference.
PMID- 27508268
TI - Single molecule force spectroscopy data and BD- and MD simulations on the blood
protein von Willebrand factor.
AB - We here give information for a deeper understanding of single molecule force
spectroscopy (SMFS) data through the example of the blood protein von Willebrand
factor (VWF). It is also shown, how fitting of rupture forces versus loading rate
profiles in the molecular dynamics (MD) loading-rate range can be used to
demonstrate the qualitative agreement between SMFS and MD simulations. The
recently developed model by Bullerjahn, Sturm, and Kroy (BSK) was used for this
demonstration. Further, Brownian dynamics (BD) simulations, which can be utilized
to estimate the lifetimes of intramolecular VWF interactions under physiological
shear, are described. For interpretation and discussion of the methods and data
presented here, we would like to directly point the reader to the related
research paper, "Mutual A domain interactions in the force sensing protein von
Willebrand Factor" (Posch et al., 2016) [1].
PMID- 27508269
TI - A description of data sets to determine the innovative diversification capacity
of farm households.
AB - This data represents research activities carried out in Co. Offaly and Co. Mayo,
Ireland, to identify farm household innovative diversification behavior and
policy/institutional actor capacity roles in support. The data sets are overlain
with household and agency data from the two study areas to describe levels of
innovative diversification capacity by individual socio-economic farm household
profile. The data sets summarize the public policy discussions on rural
innovation and diversification and policy actor response requirements, and
incorporate both qualitative and quantitative data set combinations. The data are
used to assess policy/institutional actors' roles and farm households' capacity
for innovation at the farm household/institution interface in support of
sustainable rural business innovations on-farm and diversification.
PMID- 27508270
TI - Data on morphometric analysis of the pancreatic islets from C57BL/6 and BALB/c
mice.
AB - The endocrine portion of the pancreas, which is characterized by pancreatic
islets, has been widely investigated among different species. The BALB/c and
C57BL/6 mice are extensively used in experimental research, and the morphometric
differences in the pancreatic islets of these animals have not been evaluated so
far. Thus, our data have a comparative perspective related to the morphometric
analysis of area, diameters, circularity, and density of pancreatic islets from
BALB/c and C57BL/6 mice. The data presented here are focused to evaluate the
differences in morphology of pancreatic islets of two common laboratory mouse
strains.
PMID- 27508271
TI - Serous carcinoma of endometrium in combination with neuroendocrine small-cell: A
case report and literature review.
AB - Endometrial serous carcinomas are very clinically aggressive, which constitutes
40% of all deaths and recurrences associated with endometrial cancer. Small-cell
carcinoma of the endometrium is relatively rare but aggressive, and often
presents a component of endometrioid carcinoma, and is not generally associated
with serous carcinoma. Herein, we report a case of 74-year-old African-American
female, who presented with intermittent post-menopausal bleeding for > 1-month.
She underwent robotic-assisted laparoscopic hysterectomy, bilateral salpingo
oophorectomy, sentinel lymph node mapping, and pelvic-and-aortic lymphadenectomy.
Final pathology was consistent with serous carcinoma of the endometrium in
combination with neuroendocrine small-cell carcinoma. This extremely rare
combination of tumors presents a challenge for treatment. The mainstay of
treatment seems to be surgery followed by chemotherapy +/- radiation therapy. To
our knowledge, it represents an under-reported area of gynecological medicine.
PMID- 27508272
TI - Primary ovarian neuroendocrine tumor arising in association with a mature cystic
teratoma: A case report.
AB - Primary ovarian carcinoid tumors are exceptionally rare entities accounting for
approximately 0.1% of all ovarian neoplasms. This report describes a primary
ovarian neuroendocrine tumor arising in association with a mature cystic teratoma
in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was
composed of cystic, solid and mucinous elements which resolved into a dual
component lesion histologically. The majority of the tumor displayed an organoid
architecture with mild to moderate pleomorphism and no discernible mitotic
activity, while approximately 10% consisted of sheets and groups of cells with
highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature
cystic teratoma were seen very focally. Immunohistochemistry revealed strong,
diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was
noted and there was an absence of nuclear beta-catenin accumulation. Ki-67 index
was 10-12%. Although there is no established diagnostic framework for primary
ovarian carcinoid tumors, this case was diagnosed as a well-differentiated
neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a
mature cystic teratoma/dermoid cyst. This case highlights the need to develop
ovarian diagnostic criteria in this area.
PMID- 27508273
TI - Editorial: Preventive strategies in geriatric dental medicine.
PMID- 27508274
TI - Impact of Chlorhexidine Pretreatment Followed by Probiotic Streptococcus
salivarius Strain K12 on Halitosis in Children: A Randomised Controlled Clinical
Trial.
AB - PURPOSE: The aim of this study was to examine the effect of chlorhexidine
disinfection, as a chemical method of oral hygiene practice, and subsequent use
of probiotics on halitosis in children. The effects of mechanical and chemical
oral hygiene practice methods on the severity of halitosis were also assessed.
MATERIALS AND METHODS: 208 children with organoleptic test (OLT) scores of 2 or
more were randomly assigned to four groups: A: conventional oral hygiene
practices (COH) including toothbrushing and flossing; B: COH + tongue scraping
(TS); C: COH + TS + chlorhexidine; D: COH + TS + chlorhexidine + probiotics. OLT
was performed at 1-week and 3-month follow-ups. RESULTS: A significant and stable
number of participants showed major and moderate levels of improvement in OLT
scores in group D (p < 0.001). The improvement of OLT scores in group C was also
significant (p < 0.001), but not stable over the follow-ups (p = 0.44). Neither
significant nor stable improvements in the OLT scores were detected in groups A
and B through follow-ups (p > 0.05). CONCLUSION: Probiotic therapy following oral
disinfection with chlorhexidine may reduce the severity of halitosis over longer
periods.
PMID- 27508279
TI - Determination and prediction of the magnetic anisotropy of Mn ions.
AB - This tutorial is dedicated to the investigation of magnetic anisotropy using both
electron paramagnetic resonance (EPR) spectroscopy for its experimental
determination and quantum chemistry for its theoretical prediction. Such an
approach could lead to the definition of magneto-structural correlation essential
for the rational design of complexes with targeted magnetic properties or for the
identification of unknown reactive metallic species involved in catalysis. To
illustrate this combined approach the high spin MnII, MnIII and MnIV ions have
been taken as specific examples. The first part deals with the analysis of the
EPR experiments as a function of the ions under investigation and the conditions
of the measurements, specifically: (i) EPR spectra recorded under high vs. low
frequency conditions with respect to magnetic anisotropy, (ii) EPR spectra of non
integer (Kramers) vs. integer (non-Kramers) spin states and (iii) mono- vs. multi
frequency EPR spectra. In the second part, two main quantum chemical approaches,
which have proven their capability to predict magnetic anisotropy, are described.
More importantly, these calculations give access to the different contributions
of zero field splitting, key information for the full understanding of magnetic
anisotropy. The last part demonstrates that such a combined experimental and
theoretical approach allows for the definition of magneto-structural
correlations.
PMID- 27508280
TI - Changes in the volume phase transition temperature of hydrogels for detection of
the DNA hybridization process.
AB - A simple biosensing platform which involves the application of thermoresponsive
hydrogels (p(NIPA-co-AA)) for detection of target DNA sequences is presented. For
this aim the hydrogel based on N-isopropylacrylamide grafted with carboxyl groups
was modified with H2N-ssDNA via the amide bond. The detection of target DNA
sequences was achieved successfully by monitoring the volume phase transition
temperature (VPTT). It was found that the dependence between the VPTT and the
concentration of the target complementary DNA is linear in the concentration
range from 10-12 to 10-6 M. The proposed DNA detection method is characterized by
high sensitivity and good reproducibility. The detection limit obtained (~1 pM)
is a substantial improvement over DNA biosensor labelling with tags, because the
detection is based on a physical parameter (VPTT). Circular dichroism (CD) and
inductively coupled plasma mass spectrometry with laser ablation (LA-ICP-MS)
proved that the hybridization process took place in the hydrogel matrix without
any restrictions.
PMID- 27508281
TI - Advanced gas sensors based on substrate-integrated hollow waveguides and dual
color ring quantum cascade lasers.
AB - This study shows the first combination of a ring-shaped vertically emitting
quantum cascade laser (riQCL) providing two distinct emission wavelengths
combined with a substrate-integrated hollow waveguide (iHWG). This ultra-compact
riQCL-iHWG gas sensing device enables the simultaneous detection of two vapor
phase species - here, furan and 2-methoxyethanol - providing distinctive
absorption features at the emission wavelengths of the riQCL (i.e., 1144 and 1170
cm-1). Hence, multianalyte gas sensing via a unique mid-infrared (MIR) sensor
concept is demonstrated.
PMID- 27508282
TI - Fluorescence recognition of double-stranded DNA based on the quenching of gold
nanoparticles to a fluorophore labeled DNA probe.
AB - An ultrasensitive fluorescent platform for sequence-specific recognition of
double-stranded DNA (dsDNA) based on the quenching of gold nanoparticles (AuNPs)
to a fluorophore labeled DNA probe was developed. The target dsDNA could
hybridize with the loop portion of the molecular beacon (MB) to form a triplex
DNA structure and opened the "stem-loop" structure of the MB; such triplex DNA
was used as an assistant probe (AP). Meanwhile, a fluorophore labeled DNA-AuNP
probe that contained a specific enzyme cleavage site was introduced and its
fluorescence signal was efficiently quenched due to the vicinity of the
fluorophore to the AuNP surface. Such a DNA-AuNP probe could hybridize with the
5' stem portion of the MB in the AP to form duplex DNA strands that contained a
specific enzyme cleavage site for the nicking enzyme assisted cleavage reaction,
and resulted in the release of the fluorophore from the AuNP surface and the
recovery of the fluorescence signal. Because the AP remains intact during such a
cleavage process, it could be reused to hybridize with the next DNA-AuNP probe
and trigger the nicking nuclease assisted signal amplification. Under optimal
conditions, a low detection limit of 3.8 pM was obtained for dsDNA detection, and
the assay has high sequence specificity for dsDNA detection.
PMID- 27508283
TI - Stimulated Raman photoacoustic spectroscopy for chemical-contrast imaging of a
sample deeply buried in scattering media.
AB - The development of a stimulated Raman scattering photoacoustic (SRS-PA)
spectrometer is presented. In the apparatus, a molecular vibrational mode is
excited by the SRS process. The vibrational excitation energy is converted to
heat by vibrational relaxation. The volumes around the excited molecules
including the surrounding solvent molecules expand by heating, resulting in the
generation of an ultrasonic wave. The ultrasonic wave can be used as a molecular
selective signal. Because the ultrasonic wave is scarcely scattered by media, SRS
PA is expected to be applied for obtaining molecular-selective signals from
deeply buried samples. In the present study, a SRS-PA spectrometer was developed
and applied to obtain molecular-selective signals from test samples. The SRS-PA
signals from water and lipid, which are important components in biological
systems, were first obtained. The SRS-PA signal from a polystyrene film buried in
a highly light-scattering intralipid suspension was also measured. We succeeded
in obtaining the signal from the film when it was buried with a depth of up to
1.8 mm. The results indicate that SRS-PA can be effectively applied for the
chemical-contrast imaging of deeply buried samples.
PMID- 27508284
TI - Encapsulated feeder cells within alginate beads for ex vivo expansion of cord
blood-derived CD34(+) cells.
AB - A co-culture system based on encapsulated feeder cells within alginate beads was
developed through optimizing the detailed aspects of the cell culture system to
expand CD34-positive (CD34(+)) cells ex vivo. Mesenchymal stem cells isolated
from different sources (human amniotic (hAMSCs) and umbilical cord (UCMSCs)), and
human fibroblast cells (HFs) have been respectively chosen as feeder cells and
the results showed that the hAMSCs were superior to UCMSCs and HFs in
conventional two-dimensional (2D) co-cultures regarding the promotion of total
nucleated cell (TNCs) expansion and the maintenance of the CD34(+) phenotype.
Alginate beads were employed to limit the growth of hAMSCs, which could
effectively restrict the proliferation of the encapsulated hAMSCs, while the cell
viability of hAMSCs was still highly maintained. Intriguingly, only a few hAMSCs
migrated out of the alginate beads, whereas secreted growth factors and cytokines
could be easily released. Furthermore, the alginate beads supported CD34(+)
cells/hAMSCs 2D indirect co-culture exhibited increased TNCs expansion, higher
percentages of CD34(+) and CD34(+)CD38(-) cells, and better cell vitality when
compared to the 2D co-culture. Therefore, the co-culture system based on
encapsulated hAMSCs within alginate beads can effectively promote CD34(+) cells
to expand ex vivo.
PMID- 27508285
TI - Synthesis, characterization and in vitro biocompatibility assessment of a novel
tripeptide hydrogelator, as a promising scaffold for tissue engineering
applications.
AB - We have synthesized and characterized a self-assembling tripeptide hydrogelator
Ac-l-Phe-l-Phe-l-Ala-NH2. A series of experiments showed that the hydrogel
material could serve as a stabile and biocompatible physical support as it
improves the survival of HEK293T cells in vitro, thus being a promising
biomaterial for use in tissue engineering applications.
PMID- 27508286
TI - Isolated Parotid Gland Sarcoidosis Mimicking Parotid Tumor.
PMID- 27508287
TI - Turning point: Kevin Esvelt.
PMID- 27508288
TI - Introduction to Special Issue on Imaging of Plants and Fungi.
PMID- 27508289
TI - WHO AND EXPERTS PRIORITIZE VACCINES, DIAGNOSTICS AND INNOVATIVE VECTOR CONTROL
TOOLS FOR ZIKA R&D.
PMID- 27508290
TI - WHO SUPPORTS CABO VERDE IN MANAGING ZIKA VIRUS.
PMID- 27508291
TI - Recent, Innovative Approaches to Neural Therapy and Repair: Introduction to the
ASNTR Special Issue From the 2015 Meeting.
PMID- 27508292
TI - BLUE CROSS HEALTH PLANS COLLABORATE ON OPIOID PROTOCOLS.
PMID- 27508293
TI - OBAMA UNDERLINES COLLECTIVE APPROACH TO ADDICTION CRISIS.
PMID- 27508294
TI - Directed Chemical Evolution with an Outsized Genetic Code.
AB - The first demonstration that macromolecules could be evolved in a test tube was
reported twenty-five years ago. That breakthrough meant that billions of years of
chance discovery and refinement could be compressed into a few weeks, and
provided a powerful tool that now dominates all aspects of protein engineering. A
challenge has been to extend this scientific advance into synthetic chemical
space: to enable the directed evolution of abiotic molecules. The problem has
been tackled in many ways. These include expanding the natural genetic code to
include unnatural amino acids, engineering polyketide and polypeptide synthases
to produce novel products, and tagging combinatorial chemistry libraries with
DNA. Importantly, there is still no small-molecule analog of directed protein
evolution, i.e. a substantiated approach for optimizing complex (>= 10^9
diversity) populations of synthetic small molecules over successive generations.
We present a key advance towards this goal: a tool for genetically-programmed
synthesis of small-molecule libraries from large chemical alphabets. The approach
accommodates alphabets that are one to two orders of magnitude larger than any in
Nature, and facilitates evolution within the chemical spaces they create. This is
critical for small molecules, which are built up from numerous and highly varied
chemical fragments. We report a proof-of-concept chemical evolution experiment
utilizing an outsized genetic code, and demonstrate that fitness traits can be
passed from an initial small-molecule population through to the great
grandchildren of that population. The results establish the practical feasibility
of engineering synthetic small molecules through accelerated evolution.
PMID- 27508295
TI - Impact of Decreased Serum Insulin-Like Growth Factor-1 Levels on Central Aortic
Compliance in Small-for-Gestational-Age Infants.
AB - BACKGROUND: Intrauterine growth restriction is associated with arterial
hypertension in adulthood; however, the underlying mechanism is unclear.
OBJECTIVES: We hypothesized that serum insulin-like growth factor-1 (IGF-1)
levels affect central aortic elastic properties and structure in small-for
gestational-age (SGA) infants. METHODS: Eighteen SGA infants and 22 appropriate
for-gestational-age (AGA) infants were enrolled in this study. The serum IGF-1
level within 1 h of birth and abdominal aortic echo parameters at 1 week of age
were retrospectively compared. RESULTS: In the SGA infants, IGF-1 levels (27.6 +/
17.7 vs. 42.6 +/- 15 ng/ml, p = 0.006), aortic strain (10.2 +/- 3.1 vs. 12.8 +/-
3.1%, p = 0.01), and aortic distensibility (0.73 +/- 0.19 vs. 0.92 +/- 0.34
cm2/dyn * 10-4, p = 0.05) were significantly lower compared with AGA infants. By
contrast, blood pressure, aortic intima-media thickness (aIMT) in relation to
body weight (383 +/- 163 vs. 256 +/- 43 MUm/kg, p < 0.001), aortic stiffness
index in relation to body weight (2.0 +/- 1.7 vs. 1.1 +/- 0.4, p = 0.005), and
arterial pressure-strain elastic modulus (293 +/- 72 vs. 242 +/- 78 mm Hg, p =
0.04) were higher compared with AGA infants. In the SGA infants, IGF-1 levels
were significantly correlated with aortic strain (r = 0.49, p = 0.04), aIMT in
relation to body weight (r = -0.61, p = 0.007), and aortic stiffness index in
relation to body weight (r = -0.63, p = 0.005). CONCLUSIONS: Decreased serum IGF
1 levels in SGA infants may affect the vascular compliance and structure of the
central aorta.
PMID- 27508296
TI - Grape Cultivar and Sap Culture Conditions Affect the Development of Xylella
fastidiosa Phenotypes Associated with Pierce's Disease.
AB - Xylella fastidiosa is a xylem-limited bacterium in plant hosts and causes
Pierce's disease (PD) of grapevines, which differ in susceptibility according to
the Vitis species (spp.). In this work we compared X. fastidiosa biofilm
formation and population dynamics when cultured in xylem saps from PD-susceptible
and -resistant Vitis spp. under different conditions. Behaviors in a closed
culture system were compared to those in different sap-renewal cultures that
would more closely mimic the physicochemical environment encountered in planta.
Significant differences in biofilm formation and growth in saps from PD
susceptible and -resistant spp. were only observed using sap renewal culture.
Compared to saps from susceptible V. vinifera, those from PD-resistant V.
aestivalis supported lower titers of X. fastidiosa and less biofilm and V.
champinii suppressed both growth and biofilm formation, behaviors which are
correlated with disease susceptibility. Furthermore, in microfluidic chambers X.
fastidiosa formed thick mature biofilm with three-dimensional (3-D) structures,
such as pillars and mounds, in saps from all susceptible spp. In contrast, only
small aggregates of various shapes were formed in saps from four out of five of
the resistant spp.; sap from the resistant spp. V. mustangensis was an exception
in that it also supported thick lawns of biofilm but not the above described 3-D
structures typically seen in a mature biofilm from the susceptible saps. Our
findings provide not only critical technical information for future bioassays,
but also suggest further understanding of PD susceptibility.
PMID- 27508297
TI - The Use of Antihypertensive Medication and the Risk of Breast Cancer in a Case
Control Study in a Spanish Population: The MCC-Spain Study.
AB - INTRODUCTION: The evidence on the relationship between breast cancer and
different types of antihypertensive drugs taken for at least 5 years is limited
and inconsistent. Furthermore, the debate has recently been fueled again with new
data reporting an increased risk of breast cancer among women with a long history
of use of antihypertensive drugs compared with nonusers. METHODS: In this case
control study, we report the antihypertensive drugs-breast cancer relationship in
1,736 breast cancer cases and 1,895 healthy controls; results are reported
stratifying by the women's characteristics (i.e., menopausal status or body mass
index category) tumor characteristics and length of use of antihypertensive
drugs. RESULTS: The relationship among breast cancer and use of calcium channel
blockers (CCB) for 5 or more years had odds ratio (OR) = 1.77 (95% CI, 0.99 to
3.17). Stratifying by BMI, the OR increased significantly in the group with BMI
>= 25 (OR 2.54, 95% CI, 1.24 to 5.22). CCBs were even more strongly associated
with more aggressive tumors, (OR for invasive tumors = 1.96, 95% CI = 1.09 to
3.53; OR for non ductal cancers = 3.97, 95% CI = 1.73 to 9.05; OR for Erbb2+
cancer = 2.97, 95% CI: 1.20 to 7.32). On the other hand, premenopausal women were
the only group in which angiotensin II receptor blockers may be associated with
breast cancer (OR = 4.27, 95% CI = 1.32 to 13.84) but this could not be
identified with any type or stage. Use of angiotensin-converting-enzyme
inhibitors, beta blockers and diuretics were not associated with risk.
CONCLUSIONS: In this large population-based study we found that long term use of
calcium channel blockers is associated with some subtypes of breast cancer (and
with breast cancer in overweight women).
PMID- 27508298
TI - Competing Distractors Facilitate Visual Search in Heterogeneous Displays.
AB - In the present study, we examine how observers search among complex displays.
Participants were asked to search for a big red horizontal line among 119
distractor lines of various sizes, orientations and colours, leading to 36
different feature combinations. To understand how people search in such a
heterogeneous display, we evolved the search display by using a genetic algorithm
(Experiment 1). The best displays (i.e., displays corresponding to the fastest
reaction times) were selected and combined to create new, evolved displays.
Search times declined over generations. Results show that items sharing the same
colour and orientation as the target disappeared over generations, implying they
interfered with search, but items sharing the same colour and were 12.5 degrees
different in orientation only interfered if they were also the same size.
Furthermore, and inconsistent with most dominant visual search theories, we found
that non-red horizontal distractors increased over generations, indicating that
these distractors facilitated visual search while participants were searching for
a big red horizontally oriented target. In Experiments 2 and 3, we replicated
these results using conventional, factorial experiments. Interestingly, in
Experiment 4, we found that this facilitation effect was only present when the
displays were very heterogeneous. While current models of visual search are able
to successfully describe search in homogeneous displays, our results challenge
the ability of these models to describe visual search in heterogeneous
environments.
PMID- 27508299
TI - Does Economic Growth Reduce Childhood Undernutrition in Ethiopia?
AB - BACKGROUND: Policy discussions and debates in the last couple of decades
emphasized efficiency of development policies for translating economic growth to
development. One of the key aspects in this regard in the developing world is
achieving improved nutrition through economic development. Nonetheless, there is
a dearth of literature that empirically verifies the association between economic
growth and reduction of childhood undernutrition in low- and middle-income
countries. Thus, the aim of the study is to assess the interplay between economic
growth and reduction of childhood undernutrition in Ethiopia. METHODS: The study
used pooled data of three rounds (2000, 2005 and 2010) from the Demographic and
Health Surveys (DHS) of Ethiopia. A multilevel mixed logistic regression model
with robust standard errors was utilized in order to account for the hierarchical
nature of the data. The dependent variables were stunting, underweight, and
wasting in children in the household. The main independent variable was real per
capita income (PCI) that was adjusted for purchasing power parity. This
information was obtained from World Bank. RESULTS: A total of 32,610 children
were included in the pooled analysis. Overall, 11,296 (46.7%) [46.0%-47.3%],
8,197(33.8%) [33.2%-34.4%] and 3,175(13.1%) [12.7%-13.5%] were stunted,
underweight, and wasted, respectively. We found a strong correlation between
prevalence of early childhood undernutrition outcomes and real per capita income
(PCI). The proportions of stunting (r = -0.1207, p<0.0001), wasting (r = -0.0338,
p<0.0001) and underweight (r = -0.1035, p<0.0001) from the total children in the
household were negatively correlated with the PCI. In the final model adjustment
with all the covariates, economic growth substantially reduced stunting [beta =
0.0016, SE = 0.00013, p<0.0001], underweight [beta = -0.0014, SE = 0.0002,
p<0.0001] and wasting [beta = -0.0008, SE = 0.0002, p<0.0001] in Ethiopia over a
decade. CONCLUSION: Economic growth reduces child undernutrition in Ethiopia.
This verifies the fact that the economic growth of the country accompanied with
socio-economic development and improvement of the livelihood of the poor. Direct
nutrition specific and nutrition sensitive interventions could also be
recommended in order to have an impact on the massive reduction of childhood
undernutrition in the country.
PMID- 27508300
TI - Activated Protein C Resistance Does Not Increase Risk for Recurrent Stroke or
Death in Stroke Patients.
AB - BACKGROUND: Activated protein C (APC) resistance is the most common inherited
prothrombotic disorder. The role of APC resistance in ischemic stroke is
controversially discussed. OBJECTIVES: The aim of this single center follow up
study was to investigate the effect of APC resistance on stroke recurrence and
survival in stroke patients. PATIENTS/METHODS: We retrospectively identified 966
patients who had had an ischemic stroke or transitory ischemic attack (TIA) and
in whom laboratory tests for APC resistance had been conducted. These patients
were contacted to determine the primary outcomes of recurrent ischemic stroke or
death. RESULTS: A total of 858 patients with an average follow up time of 8.48
years were included. APC resistance did not influence cumulative incidence
functions for stroke free and total survival. In multivariate analyses, crude and
adjusted hazard ratios for recurrent stroke as well as for death where not
significantly increased in patients with APC resistance. This also applies to the
subgroups of young patients, patients with cryptogenic stroke and patients with
atrial fibrillation. CONCLUSION: APC-resistance is not a risk factor for
subsequent stroke or death in patients with a first ischemic stroke or TIA.
Testing for APC-resistance in stroke patients therefore cannot be routinely
recommended.
PMID- 27508301
TI - Incidence of Diabetes Mellitus and Obesity and the Overlap of Comorbidities in
HIV+ Hispanics Initiating Antiretroviral Therapy.
AB - BACKGROUND: Cardiovascular disease (CVD) is a leading health threat for HIV+
patients on antiretroviral therapy (ART); cardiometabolic comorbidities are key
predictors of risk. Data are limited on incidence of metabolic comorbidities in
HIV+ individuals initiating ART in low and middle income countries (LMICs),
particularly for Hispanics. We examined incidence of diabetes and obesity in a
prospective cohort of those initiating ART in the Dominican Republic. METHODS:
Participants >=18 years, initiating ART <90 days prior to study enrollment, were
examined for incidence of impaired fasting glucose (IFG), diabetes mellitus (DM),
overweight, and obesity. Fasting plasma glucose (FPG) 100-125mg/dl defined IFG;
FPG >=126 mg/dl, diagnosis per medical record, or use of hypoglycemic medication
defined DM. Overweight and obesity were BMI 25-30 and >=30kg/m2, respectively.
Dyslipidemia was total cholesterol >=240mg/dl or use of lipid-lowering
medication. Framingham risk equation was used to determine ten-year CVD risk at
the end of observation. RESULTS: Of 153 initiating ART, 8 (6%) had DM and 23
(16%) had IFG at baseline, 6 developed DM (28/1000 person-years follow up [PYFU])
and 46 developed IFG (329/1000 PYFU). At baseline, 24 (18%) were obese and 36
(27%) were overweight, 15 became obese (69/1000 PYFU) and 22 became overweight
(163/1000 PYFU). Median observation periods for the diabetes and obesity analyses
were 23.5 months and 24.3 months, respectively. Increased CVD risk (>=10% 10-year
Framingham risk score) was present for 13% of the cohort; 79% of the cohort had
>=1 cardiometabolic comorbidity, 48% had >=2, and 13% had all three. CONCLUSIONS:
In this Hispanic cohort in an LMIC, incidences of IFG/DM and overweight/obesity
were similar to or higher than that found in high income countries, and
cardiometabolic disorders affected three-quarters of those initiating ART. Care
models incorporating cardiovascular risk reduction into HIV treatment programs
are needed to prevent CVD-associated mortality in this vulnerable population.
PMID- 27508302
TI - Epitope Mapping of a Monoclonal Antibody Directed against Neisserial Heparin
Binding Antigen Using Next Generation Sequencing of Antigen-Specific Libraries.
AB - We explore here the potential of a newly described technology, which is named
PROFILER and is based on next generation sequencing of gene-specific lambda phage
displayed libraries, to rapidly and accurately map monoclonal antibody (mAb)
epitopes. For this purpose, we used a novel mAb (designated 31E10/E7) directed
against Neisserial Heparin-Binding Antigen (NHBA), a component of the anti-group
B meningococcus Bexsero(r) vaccine. An NHBA phage-displayed library was affinity
selected with mAb 31E10/E7, followed by massive sequencing of the inserts present
in antibody-selected phage pools. Insert analysis identified an amino acid
stretch (D91-A128) in the N-terminal domain, which was shared by all of the mAb
enriched fragments. Moreover, a recombinant fragment encompassing this sequence
could recapitulate the immunoreactivity of the entire NHBA molecule against mAb
31E10/E7. These results were confirmed using a panel of overlapping recombinant
fragments derived from the NHBA vaccine variant and a set of chemically
synthetized peptides covering the 10 most frequent antigenic variants.
Furthermore, hydrogen-deuterium exchange mass-spectrometry analysis of the NHBA
mAb 31E10/E7 complex was also compatible with mapping of the epitope to the D91
A128 region. Collectively, these results indicate that the PROFILER technology
can reliably identify epitope-containing antigenic fragments and requires
considerably less work, time and reagents than other epitope mapping methods.
PMID- 27508303
TI - IRF1 Downregulation by Ras/MEK Is Independent of Translational Control of IRF1
mRNA.
AB - Oncogenic activation of Ras/MEK downregulates the expression of interferon
regulatory factor 1 (IRF1), which is a prerequisite for oncolytic viruses to
replicate in cancer cells [1]. Moreover, restoration of IRF1 expression is
essential to induce apoptosis of cancer cells treated with a MEK inhibitor [2].
However, the molecular mechanisms that underlie IRF1 downregulation by Ras/MEK
remain unclear. In this study, we determined whether Ras/MEK activation modulates
IRF1 expression at its translational level. MEK inhibition increased the activity
of IRF1 promoter construct in Ras transformed NIH3T3 cells and wild type MEF, but
not in IRF1 deficient MEF, indicating that IRF1 protein is required for the
transcriptional activation of IRF1. By conducting reporter analysis using IRF1 5'
and 3'- UTR constructs, we determined that cis elements on 5'- and 3'-UTR of
IRF1 mRNA are not involved in the IRF1 regulation by Ras/MEK. We further compared
the recruitment of ribosomes to IRF1 mRNA in RasV12 cells treated with or without
the MEK inhibitor by conducting polysome analysis. No difference was observed in
the polysomal distribution of IRF1 mRNA between RasV12 cells treated with and
without the MEK inhibitor. These results suggest that regulation of IRF1
translation is independent of IRF1 downregulation by Ras/MEK.
PMID- 27508306
TI - Heterometallic Co(III)-Gd(III) Clusters as Magnetic Refrigerants.
AB - Two heterometallic Co(III)-Gd(III) nanomagnets (Co2Gd6 and Co2Gd9) with defective
dicubane-like cores were isolated from the same set of reactants by varying the
reaction conditions. These are the first examples of cobalt(III)-gadolinium(III)
phosphonate compounds and a rare class of compounds with large 4f ratio among the
reported 3d-4f complexes. Magnetic studies reveal large magnetic entropy changes
for both complexes (-DeltaSm = 27.81 and 33.07 J kg(-1) K(-1), respectively at 3
K and 7 T).
PMID- 27508305
TI - Determining the Effect of Natural Selection on Linked Neutral Divergence across
Species.
AB - A major goal in evolutionary biology is to understand how natural selection has
shaped patterns of genetic variation across genomes. Studies in a variety of
species have shown that neutral genetic diversity (intra-species differences) has
been reduced at sites linked to those under direct selection. However, the effect
of linked selection on neutral sequence divergence (inter-species differences)
remains ambiguous. While empirical studies have reported correlations between
divergence and recombination, which is interpreted as evidence for natural
selection reducing linked neutral divergence, theory argues otherwise, especially
for species that have diverged long ago. Here we address these outstanding issues
by examining whether natural selection can affect divergence between both closely
and distantly related species. We show that neutral divergence between closely
related species (e.g. human-primate) is negatively correlated with functional
content and positively correlated with human recombination rate. We also find
that neutral divergence between distantly related species (e.g. human-rodent) is
negatively correlated with functional content and positively correlated with
estimates of background selection from primates. These patterns persist after
accounting for the confounding factors of hypermutable CpG sites, GC content, and
biased gene conversion. Coalescent models indicate that even when the
contribution of ancestral polymorphism to divergence is small, background
selection in the ancestral population can still explain a large proportion of the
variance in divergence across the genome, generating the observed correlations.
Our findings reveal that, contrary to previous intuition, natural selection can
indirectly affect linked neutral divergence between both closely and distantly
related species. Though we cannot formally exclude the possibility that the
direct effects of purifying selection drive some of these patterns, such a
scenario would be possible only if more of the genome is under purifying
selection than currently believed. Our work has implications for understanding
the evolution of genomes and interpreting patterns of genetic variation.
PMID- 27508307
TI - Asymmetric Reduction of Lactam-Based beta-Aminoacrylates. Synthesis of
Heterocyclic beta(2)-Amino Acids.
AB - The ability to affect asymmetric reduction of heterocyclic beta-aminoacrylates 1
(n = 1-3) has been assessed with pyrrolidine and piperidone variants generating
the corresponding N-heterocyclic beta(2)-amino acids 3b and 5b with high
enantioselectivity (>=97% ee) using a Rh/WALPHOS catalyst combination. The use of
the carboxylic acid substrate was essential; the corresponding esters do undergo
reduction but led to racemic products. The seven-ring azepanone variant (as the
carboxylic acid 9b) underwent reduction, but only a minimal level of asymmetric
induction was observed.
PMID- 27508308
TI - Boesenberols, Pimarane Diterpenes with TRAIL-Resistance-Overcoming Activity from
Boesenbergia pandurata.
AB - TRAIL is a potent and selective inducer of apoptosis in most cancer cells while
sparing normal cells, which makes it an attractive target for the development of
new cancer therapies. In a screening program on natural resources with the
ability to abrogate TRAIL resistance, the bioassay-guided fractionation of
Boesenbergia pandurata rhizomes resulted in the isolation of 17 pimarane
diterpenes and a monoterpene. Among these, compounds 1-8, named boesenberols A-H,
are new pimarane diterpenes. All compounds exhibited TRAIL-resistance-overcoming
activity in TRAIL-resistant AGS cells. Subtoxic doses of the major compound 9
sensitized AGS cells to TRAIL-induced apoptosis by up-regulating apoptosis
inducing proteins, such as DR4, DR5, p53, Fas, CHOP, Bak, and cleaved caspases-3,
-8, and -9, and down-regulating the levels of cell survival proteins, such as Bcl
2, c-FLIP, and GSK-3beta, in TRAIL-resistant AGS cells. Furthermore, compound 9
did not decrease the viability of noncancerous (HEK293) cells at concentrations
up to 30 MUM.
PMID- 27508309
TI - Inoculation of Brassica oxyrrhina with plant growth promoting bacteria for the
improvement of heavy metal phytoremediation under drought conditions.
AB - The aim of this study was to investigate the effects of drought resistant
serpentine rhizobacteria on plant growth and metal uptake by Brassica oxyrrhina
under drought stress (DS) condition. Two drought resistant serpentine
rhizobacterial strains namely Pseudomonas libanensis TR1 and Pseudomonas reactans
Ph3R3 were selected based on their ability to stimulate seedling growth in roll
towel assay. Further assessment on plant growth promoting (PGP) parameters
revealed their ability to produce indole-3-acetic acid, siderophore and 1
aminocyclopropane-1-carboxylate deaminase. Moreover, both strains exhibited high
resistance to various heavy metals, antibiotics, salinity and extreme
temperature. Inoculation of TR1 and Ph3R3 significantly increased plant growth,
leaf relative water and pigment content of B. oxyrrhina, whereas decreased
concentrations of proline and malondialdehyde in leaves under metal stress in the
absence and presence of DS. Regardless of soil water conditions, TR1 and Ph3R3
greatly improved organ metal concentrations, translocation and bioconcentration
factors of Cu and Zn. The successful colonization and metabolic activities of P.
libanensis TR1 and P. reactans Ph3R3 represented positive effects on plant
development and metal phytoremediation under DS. These results indicate that
these strains could be used as bio-inoculants for the improvement of
phytoremediation of metal polluted soils under semiarid conditions.
PMID- 27508310
TI - Solution Nuclear Magnetic Resonance Studies of Sterol Carrier Protein 2 Like 2
(SCP2L2) Reveal the Insecticide Specific Structural Characteristics of SCP2
Proteins in Aedes aegypti Mosquitoes.
AB - Sterol carrier protein 2 like 2 from Aedes aegypti (AeSCP2L2) plays an important
role in lipid transport in mosquitoes for its routine metabolic processes.
Repeated unsuccessful attempts to crystallize ligand free SCP2L2 prompted us to
undertake nuclear magnetic resonance (NMR) spectroscopy to determine its three
dimensional structure. We report here the three-dimensional structures and
dynamics of apo-AeSCP2L2 and its complex with palmitate. The (15)N heteronuclear
single-quantum coherence spectrum of apo-AeSCP2L2 displayed multiple peaks for
some of the amide resonances, implying the presence of multiple conformations in
solution, which are transformed to a single conformation upon formation of the
complex with plamitate. The three-dimensional structures of apo-AeSCP2L2 and
palmitated AeSCP2L2 reveal an alpha/beta mixed fold, with five beta-strands and
four alpha-helices, very similar to the other SCP2 protein structures. Unlike the
crystal structure of palmitated AeSCP2L2, both solution structures are monomeric.
It is further confirmed by the rotational correlation times determined by NMR
relaxation times (T1 and T2) of the amide protons. In addition, the palmitated
AeSCP2L2 structure contains two palmitate ligands, bound in the binding pocket,
unlike the three palmitates bound in the dimeric form of AeSCP2L2 in the
crystals. The relaxation experiments revealed that complex formation
significantly reduces the dynamics of the protein in solution.
PMID- 27508311
TI - Hypertension and Diabetic Nephropathy.
PMID- 27508312
TI - Development of Nano-Sulfide Sorbent for Efficient Removal of Elemental Mercury
from Coal Combustion Fuel Gas.
AB - The surface area of zinc sulfide (ZnS) was successfully enlarged using
nanostructure particles synthesized by a liquid-phase precipitation method. The
ZnS with the highest surface area (named Nano-ZnS) of 196.1 m(2).g(-1) was then
used to remove gas-phase elemental mercury (Hg(0)) from simulated coal combustion
fuel gas at relatively high temperatures (140 to 260 degrees C). The Nano-ZnS
exhibited far greater Hg(0) adsorption capacity than the conventional bulk ZnS
sorbent due to the abundance of surface sulfur sites, which have a high binding
affinity for Hg(0). Hg(0) was first physically adsorbed on the sorbent surface
and then reacted with the adjacent surface sulfur to form the most stable mercury
compound, HgS, which was confirmed by X-ray photoelectron spectroscopy analysis
and a temperature-programmed desorption test. At the optimal temperature of 180
degrees C, the equilibrium Hg(0) adsorption capacity of the Nano-ZnS (inlet Hg(0)
concentration of 65.0 MUg.m(-3)) was greater than 497.84 MUg.g(-1). Compared with
several commercial activated carbons used exclusively for gas-phase mercury
removal, the Nano-ZnS was superior in both Hg(0) adsorption capacity and
adsorption rate. With this excellent Hg(0) removal performance, noncarbon Nano
ZnS may prove to be an advantageous alternative to activated carbon for Hg(0)
removal in power plants equipped with particulate matter control devices, while
also offering a means of reusing fly ash as a valuable resource, for example as a
concrete additive.
PMID- 27508313
TI - The investigation of the cellular electrophysiological and antiarrhythmic effects
of a novel selective sodium-calcium exchanger inhibitor, GYKB-6635, in canine and
guinea-pig hearts.
AB - The sodium-calcium exchanger (NCX) is considered as the major transmembrane
transport mechanism that controls Ca2+ homeostasis. Its contribution to the
cardiac repolarization has not yet been directly studied due to lack of specific
inhibitors, so that an urgent need for more selective compounds. In this study,
the electrophysiological effects of GYKB-6635, a novel NCX inhibitor, on the NCX,
L-type calcium, and main repolarizing potassium currents as well as action
potential (AP) parameters were investigated. Ion currents and AP recordings were
investigated by applying the whole-cell patch clamp and standard microelectrode
techniques in canine heart at 37 degrees C. Effects of GYKB-6635 were studied in
ouabain-induced arrhythmias in isolated guinea-pig hearts. At a concentration of
1 MUmol/L, GYKB significantly reduced both the inward and outward NCX currents
(57% and 58%, respectively). Even at a high concentration (10 MUmol/L), GYKB-6635
did not change the ICaL, the maximum rate of depolarization (dV/dtmax), the main
repolarizing K+ currents, and the main AP parameters. GYKB-6635 pre-treatment
significantly delayed the time to the development of ventricular fibrillation (by
about 18%). It is concluded that GYKB-6635 is a potent and highly selective
inhibitor of the cardiac NCX and, in addition, it is suggested to also contribute
to the prevention of DAD-based arrhythmias.
PMID- 27508314
TI - The effectiveness of a comprehensive reminder system in the secondary prevention
of hypertensive ischaemic stroke: randomized controlled trial protocol.
AB - AIM: The aim of this study was to determine whether the Comprehensive Reminder
System based on the Health Belief Model improves health belief, health
behaviours, medication adherence and blood pressure control as a means of
decreasing the rate of stroke recurrence among hypertensive ischaemic stroke.
BACKGROUND: Hypertensive patients having experienced recent ischaemic strokes are
at high risk for stroke recurrence. Several trials attempted to improve secondary
stroke prevention via patient education, however, patient outcomes remained poor.
Long-term follow-up studies regarding secondary stroke prevention are limited.
DESIGN: A multi-centre, 12-month, assessor-blinded, parallel-group, randomized
controlled longitudinal trial. METHODS: Hypertensive patients having experienced
an ischaemic stroke are the target population. The intervention consists of
health belief education, a calendar handbook, a weekly automated short-message
service and four telephone follow-up interviews. Outcomes will be assessed at
baseline and at 3, 6 and 12 months following discharge. The primary outcome is
blood pressure control. The secondary outcomes include health belief, health
behaviours and medication adherence. The clinical endpoint is the rate of stroke
recurrence. DISCUSSION: Although many efforts to improve secondary stroke
prevention have been undertaken, research indicates that improvements remain
possible and warranted. This research protocol based on the Health Belief Model
will improve our understanding of stroke education and transitional care needed
in China and with the world-wide target population.
PMID- 27508315
TI - Effect of the Keto Group on Yields and Composition of Organic Aerosol Formed from
OH Radical-Initiated Reactions of Ketones in the Presence of NOx.
AB - Yields of secondary organic aerosol (SOA) were measured for OH radical-initiated
reactions of the 2- through 6-dodecanone positional isomers and also n-dodecane
and n-tetradecane in the presence of NOx. Yields decreased in the order n
tetradecane > dodecanone isomer average > n-dodecane, and the dodecanone isomer
yields decreased as the keto group moved toward the center of the molecule, with
6-dodecanone being an exception. Trends in the yields can be explained by the
effect of carbon number and keto group presence and position on product vapor
pressures, and by the isomer-specific effects of the keto group on branching
ratios for keto alkoxy radical isomerization, decomposition, and reaction with
O2. Most importantly, results indicate that isomerization of keto alkoxy radicals
via 1,5- and 1,6-H shifts are significantly hindered by the presence of a keto
group whereas decomposition is enhanced. Analysis of particle composition
indicates that the SOA products are similar for all isomers, and that compared to
those formed from the corresponding reactions of alkanes the presence of a pre
existing keto group opens up additional heterogeneous/multiphase reaction
pathways that can lead to the formation of new products. The results demonstrate
that the presence of a keto group alters gas and particle phase chemistry and
provide new insights into the potential effects of molecular structure on the
products of the atmospheric oxidation of volatile organic compounds and
subsequent formation of SOA.
PMID- 27508316
TI - Stealthy role of size-driven stresses in biomechanics of breast implants capsular
contracture.
AB - Breast Capsular Contracture (BCC) is one of the adverse complications occurring
with greater incidence in breast augmentation surgical procedures. Its formation
can be interpreted as the conclusive result of the physiological process known as
response to a foreign body. From a biochemical standpoint, the formation of the
peri-prosthetic capsule is certainly a multifactorial process: many hypotheses
concerning its etiology have been suggested in the literature and a number of
related pharmacological protocols have been consequently proposed to clinically
treat this pathology with the aim to prevent further complications and avoid
future re-interventions. However, the vast majority of these theories seems to be
only partially supported by clinical outcomes and thus a shared opinion on this
matter is still absent among specialists. Within this framework, by starting from
clinical observations which highlighted an unexpected correlation between histo
morphological features of fibrotic capsules and overall size of breast implants,
the present study investigates the hypothesis that the biomechanical interaction
between prosthesis and host tissue may play a crucial role in the biological
processes governing the pathological phenomenon at hand. Therefore, to shed light
on the underlying mechanisms which could trigger the breast capsular contracture,
both simple analytical solutions, in which elasticity and growth are
simultaneously taken into account, and more accurate geometrically faithful
Finite Element-based numerical simulations have been exploited. The theoretical
findings demonstrate that somehow counter-intuitive radial and hoop stress fields
occur at the capsula-implant interface in a way such that their combined action,
independently from other possible concurrent factors, results significantly
amplified for small-size breast prostheses, localized stress peaks in these cases
promoting detaching and rippling phenomena actually observed in BCC clinical
complications.
PMID- 27508317
TI - Circulating Des-gamma-carboxy prothrombin is not associated with cardiovascular
calcification or stiffness: The Multi-Ethnic Study of Atherosclerosis (MESA).
AB - BACKGROUND AND AIMS: Vitamin K-dependent protein (VKDP) activity may have a role
in preventing cardiovascular calcification, but has not previously been studied
in large, generally healthy populations. METHODS: Using an elevated ankle
brachial index (ABI) as a measure of medial vascular calcification, we performed
a case-cohort analysis within the Multi-Ethnic Study of Atherosclerosis,
measuring Des-gamma-carboxy prothrombin (DCP) to estimate VKDP activity. In
secondary analyses of the weighted subcohort, we examined the cross-sectional
associations between DCP and prevalent vascular calcification of the coronary
vessels, aortic and mitral valves, and aortic wall, and with vascular stiffness.
RESULTS: In adjusted analysis, cases (n = 104) had 0.21 ng/ml (-0.94-0.52) lower
DCP concentrations than the subcohort (n = 613). Furthermore, amongst the 717
participants in the weighted cohort, VKDP activity was not associated with
coronary artery, mitral valve, aortic valve or aortic wall calcification, nor was
it associated with vascular stiffness. CONCLUSIONS: Our negative results do not
support a role of circulating VKDP activity in cardiovascular calcification in
community-dwelling adults.
PMID- 27508318
TI - Association of serum mimecan with angiographic coronary collateralization in
patients with stable coronary artery disease and chronic total occlusion.
AB - BACKGROUND AND AIMS: Mimecan/osteoglycin is identified as an emerging biomarker
of coronary atherosclerosis. We investigated whether and to what extent serum
mimecan reflects angiographic coronary collateralization in patients with stable
coronary artery disease and chronic total occlusion. METHODS: Serum levels of
mimecan were determined in 559 consecutive patients with stable angina and
angiographic total occlusion of at least one major coronary artery. The degree of
collaterals supplying the distal aspect of a total occlusion from the contra
lateral vessel was graded as poor (Rentrop score of 0 or 1) or good coronary
collateralization (Rentrop score of 2 or 3). RESULTS: Serum mimecan was
significantly higher in patients with poor collateralization than in those with
good collateralization, and correlated inversely with Rentrop score (adjusted
Spearmen's r = -0.443, p < 0.001). The prevalence of poor coronary collaterals
increased stepwise from the lowest to the highest quartile of serum mimecan (OR
2.140, 95% CI 1.793-2.555; p for trend < 0.001). After adjusting for age, gender,
traditional risk factors for coronary artery disease, history of myocardial
infarction, severity of coronary artery disease, renal function and C-reactive
protein, serum mimecan (per SD) remained an independent determinant for poor
collateralization (OR 2.674, 95% CI 2.057-3.475, p < 0.001). The diagnostic value
of mimecan (per SD) for detecting poor collateralization was consistent when the
patients were specified by gender, age, body mass index, presence or absence of
hypertension and diabetes, and status of renal function (OR 2.075-6.932, p
interaction >= 0.059). CONCLUSION: Increased serum mimecan is associated with
poor angiographic coronary collateralization in patients with chronic total
occlusion.
PMID- 27508319
TI - Angiographic progression of coronary atherosclerosis in patients with familial
hypercholesterolaemia treated with non-statin therapy: Impact of a fat-modified
diet and a resin.
AB - BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) profoundly increases the
risk of coronary artery disease (CAD). We investigated whether diet and a bile
acid sequestrant decrease coronary atherosclerosis in patients with FH. METHODS:
We identified 26 men with FH and CAD, participating in the St Thomas'
Atherosclerosis Regression Study, who had been randomized to receive a fat
modified diet plus cholestyramine (8 g twice daily) (DC, n = 12) or usual care
(UC, n = 14), and investigated the relative effects of these treatments on the
angiographic progression of coronary atherosclerosis over 39 months. FH was
defined as probable/definite according to Dutch Lipid Clinic Network criteria;
mean FH score was 8.7 (range 6-15) and mean baseline low-density lipoprotein
cholesterol (LDL-Ch) concentration was 5.4 (SD 1.4) mmol/L. Coronary
atherosclerosis was assessed by serial quantitative angiography as the global
changes in mean and minimum absolute width of segments (MAWS and MinAWS,
respectively). RESULTS: Mean plasma LDL-Ch concentration fell by 35% with DC and
remained significantly (p < 0.001) lower during the trial at 3.78 (SD 0.98)
mmol/L compared with UC at 4.89 (1.04). MAWS decreased by 0.252 (SEM 0.072) mm in
the UC group and by 0.001 (0.065) mm in the DC group (p = 0.007), with
corresponding reductions in MinAWS of 0.290 (0.087) mm and 0.013 (0.058) mm (p =
0.009); these changes were significant after adjusting for baseline variables,
including coronary luminal dimensions and lipoprotein(a). Progression was
observed in 7 patients (50%) on UC and 3 (25%) on DC (p = 0.19), with regression
in no patients (0%) and 3 patients (25%) (p < 0.05), respectively. CONCLUSIONS:
This investigation, carried out in the pre-statin era, demonstrates that a
prudent diet and cholestyramine could improve the course of coronary
atherosclerosis in men with phenotypic FH through sustained reductions in LDL-Ch.
PMID- 27508320
TI - Altered relation of the renin-aldosterone system and vasoactive peptides in type
2 diabetes: The KORA F4 study.
AB - BACKGROUND AND AIMS: The exact mechanism of premature atherosclerosis in diabetes
is still unclear. Inappropriate activation of the renin-aldosterone-angiotensin
system may be an important risk factor for cardiovascular disease. We
investigated whether renin and aldosterone are associated with vasoactive
peptides midregional-pro atrial natriuretic peptide (MR-proANP) and midregional
pro adrenomedullin (MR-proADM), or with intima media thickness (IMT) as a marker
for early atherosclerotic alterations in the general community and in subjects
with type 2 diabetes. METHODS: In 1261 participants in the KORA F4 study, the
associations of renin, aldosterone and aldosterone to renin ratio with MR-proANP,
MR-proADM and IMT were assessed using linear regression models stratified for the
presence of prediabetes and type 2 diabetes. RESULTS: After adjustment for
confounding factors, an inverse association of MR-proANP with renin (p = 0.002)
and aldosterone (p = 0.021) and a direct association of MR-proADM with renin (p <
0.001) and aldosterone (p = 0.019) were seen in nondiabetic individuals. In
diabetic subjects, there was no significant correlation of MR-proANP or MR-proADM
with renin or aldosterone. Renin and aldosterone were not directly associated
with IMT in non-diabetic subjects and the total cohort, whereas aldosterone was
associated with IMT in diabetic participants (p = 0.005). CONCLUSIONS: This study
shows associations between renin, aldosterone and MR-proANP/MR-proADM plasma
levels that are altered in type 2 diabetes. Plasma renin and aldosterone are not
independent biomarkers for early atherosclerotic damages of the carotid arteries
in the general community.
PMID- 27508321
TI - Intralesional meglumine antimoniate for the treatment of localised cutaneous
leishmaniasis: a retrospective review of a Brazilian referral centre.
AB - Although intralesional meglumine antimoniate (MA) infiltration is considered an
option for cutaneous leishmaniasis (CL) therapy and is widely used in the Old
World, there have been few studies supporting this therapeutic approach in the
Americas. This study aims to describe outcomes and adverse events associated with
intralesional therapy for CL. This retrospective study reviewed the experience of
a Brazilian leishmaniasis reference centre using intralesional MA to treat 31
patients over five years (2008 and 2013). The median age was 63 years (22-86) and
the median duration time of the lesions up to treatment was 16 weeks. In 22
patients (71%), intralesional therapy was indicated due to the presence of
contraindications or previous serious adverse events with systemic MA. Other
indications were failure of systemic therapy or ease of administration.
Intralesional treatment consisted of one-six infiltrations (median three) for a
period of up to 12 weeks. The initial (three months) and definitive (six months)
cure rates were 70.9% and 67.7%, respectively. Most patients reported mild
discomfort during infiltration and no serious adverse events were observed. In
conclusion, these results show that the intralesional MA efficacy rate was very
similar to that of systemic MA treatment, and reinforce the need for further
studies with adequate design to establish the efficacy and safety of this
therapeutic approach.
PMID- 27508322
TI - Comparative growth of spotted fever group Rickettsia spp. strains in Vero cells.
AB - In Brazil, the spotted fever group (SFG) Rickettsia rickettsii and Rickettsia
parkeri related species are the etiological agents of spotted fever
rickettsiosis. However, the SFG, Rickettsia rhipicephali, that infects humans,
has never been reported. The study of growth dynamics can be useful for
understanding the infective and invasive capacity of these pathogens. Here, the
growth rates of the Brazilian isolates R. rickettsii str. Taiacu, R. parkeri str.
At#24, and R. rhipicephali HJ#5, were evaluated in Vero cells by quantitative
polymerase chain reaction. R. rhipicephali showed different kinetic growth
compared to R. rickettsii and R. parkeri.
PMID- 27508323
TI - Single-Molecule Imaging of Iron-Phthalocyanine-Catalyzed Oxygen Reduction
Reaction by in Situ Scanning Tunneling Microscopy.
AB - We report herein an in situ electrochemical scanning tunneling microscopy (ECSTM)
investigation of iron-phthalocyanine (FePc)-catalyzed oxygen reduction reaction
(ORR). A highly ordered FePc adlayer is revealed on a Au(111) electrode. The
center ions in the FePc adlayer show uniform high contrast in an oxygen-saturated
electrolyte, which is attributed to the formation of an FePc-O2 complex. In situ
STM results reveal the sharp contrast change upon shifting the electrode
potential to trigger the ORR. Theoretical simulation has supplied further
evidence for the contrast difference of the adsorbed FePc species.
PMID- 27508324
TI - MicroRNA-19b Mediates Lung Epithelial-Mesenchymal Transition via
Phosphatidylinositol-3,4,5-Trisphosphate 3-Phosphatase in Response to Mechanical
Stretch.
AB - Lung epithelial-mesenchymal transition (EMT) plays an important role in
ventilation-associated lung fibrosis, which may contribute to the poor outcome of
patients with acute respiratory distress syndrome. Because microRNAs control and
modulate normal physiological and pathophysiological processes, we investigated
the role of microRNAs in the development of acute respiratory distress syndrome
associated EMT in response to mechanical stress. In the current study, primary
human alveolar epithelial type II (AEII) cells were subjected to cyclic stretch
that resulted in EMT profiles with decreased gene expression of cytokeratin-8, E
cadherin, and surfactant protein B, and increased expression of vimentin, alpha
smooth muscle actin, and N-cadherin. Microarray analysis revealed that the
expression of microRNA-19b (miR-19b) was up-regulated in the AEII cells, and real
time polymerase chain reaction showed that the expression of miR-19b increased in
both the AEII cells and the primary human small-airway epithelial cells.
Overexpression of miR-19b in small-airway epithelial cells promoted the
mechanical stretch-induced EMT phenotypes, whereas inhibition of miR-19b
attenuated it. The inhibitory effect of miR-19b was attributed to enhanced
signaling of phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN),
leading to inactivation of the AKT pathway. Restoration of PTEN expression or
inhibition of AKT phosphorylation suppressed the mechanical stretch-induced EMT
phenotypes. We further demonstrated that the mechanical stretch-induced miR19
expression was regulated by the focal adhesion kinase-Rho pathway. In conclusion,
we found that miR-19b plays a key role in the development of the EMT phenotype
through down-regulation of PTEN in human lung epithelial cells in response to
mechanical stretch. The miR-19b-PTEN signaling pathway may serve as a novel
therapeutic target in the context of ventilator-associated lung fibrosis.
PMID- 27508325
TI - Therapeutic outcomes of endoscopic submucosal dissection for early gastric
cancer: single-center study.
AB - OBJECTIVES: Endoscopic submucosal dissection (ESD) has been widely accepted for
selected patients with early gastric cancer (EGC). The aim of this study was to
assess the therapeutic outcomes after ESD according to the pathological extent.
PATIENTS AND METHODS: From January 2005 to December 2014, a total of 599 patients
with 611 lesions were enrolled in this study. The tumors were categorized
according to pathological results on the basis of absolute criteria (AC),
expanded criteria (EC), EC with undifferentiated histology [(EC-U), mucosal
cancer, ulcer (-), <=20 mm], or beyond EC (BEC). The therapeutic outcomes among
the four groups were analyzed retrospectively. RESULTS: The number of patients in
the AC, EC, EC-U, and BEC groups was 447, 91, 19, and 54. The complete resection
rates of EGC were 97.8, 84.6, 94.4, and 45.5% (P=0.001) and en bloc resection
rates in the AC, EC, EC-U, and BEC groups were 99.1, 98.9, 100, and 98.1%
(P=0.833), respectively. The 5-year disease-free survival rate in the AC, EC, EC
U, and BEC groups was 90.6, 88.7, 75.0, and 83.3% (P=0.394). In multivariate
analysis, undifferentiated histology (P=0.001) and tumor size (>30 mm, P=0.017)
were risk factors related to local recurrence. CONCLUSION: The efficacy of ESD
for EGCs in EC is almost equal to that in AC when complete resection was
achieved. However, the indication for ESD should be decided conservatively
because the complete resection rate of EGC in the EC group was significantly
lower than that in the AC group. Undifferentiated histology and tumor size over
30 mm were risk factors related to local recurrence.
PMID- 27508326
TI - Detection of molecular bacterascites in decompensated cirrhosis defines a risk
with decreased survival.
AB - BACKGROUND: The prognostic relevance of bacterial DNA (bactDNA) detection in
ascitic fluid of patients with cirrhosis is still under debate. Using
quantitative real-time PCR with broad-range primers targeting the V3 and V4
variable region of the 16S rRNA gene, we measured bactDNA concentrations in
patients with and without leukocytic ascites and evaluated the impact on short
term survival. PATIENTS AND METHODS: Ascites samples from 173 patients with
decompensated cirrhosis were consecutively collected between February 2011 and
December 2012. BactDNA-positive ascites samples were sequenced and chromatograms
were identified using RipSeq. Clinical data collection and survival analyses were
carried out retrospectively and correlated with ascites bactDNA levels. RESULTS:
BactDNA was detected qualitatively with a similar frequency in both nonleukocytic
and leukocytic ascites [40% (57/144) and 43.5% (10/23), respectively; P=0.724].
However, the median bactDNA level was significantly higher in leukocytic ascites
than in nonleukocytic ascites (1.2*10 vs. 5.7*10 copies/ml; P=0.008). Patients'
survival was associated significantly with bactDNA level. The 30-day and 180-day
survival was reduced if bactDNA was above the quantification limit of 520
copies/ml (84 and 63% vs. 72 and 43%, respectively; P<0.05) and worst if bactDNA
was above 5000 copies/ml. The bacterial spectrum was dominated by Gram-positive
strains as shown by direct sequencing. CONCLUSION: BactDNA quantification in
ascitic fluid samples using culture-independent 16S rRNA gene-based methods seems
to be an interesting approach to identify patients at risk of reduced survival.
Our study warrants further evaluation of antibiotic treatment in patients with
molecular bacterascites.
PMID- 27508327
TI - A 1-year prospective study of the effect of infliximab on bone metabolism in
inflammatory bowel disease patients.
AB - OBJECTIVES: Infliximab (IFX) treatment has shown potentially beneficial effects
on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to
prospectively evaluate the impact of IFX treatment on bone metabolism in
antitumour necrosis factor (TNF)-alpha-naive IBD patients using established bone
metabolism markers and an in-vitro osteoblast model. MATERIALS AND METHODS: A
total of 37 anti-TNFalpha-naive IBD patients and 20 healthy controls were
included. All measurements were performed at baseline and repeated in IBD
patients following IFX therapy. Bone mineral density was measured by dual-energy
X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble
receptor activator of nuclear factor B ligand and proinflammatory and anti
inflammatory cytokines were measured. Bone formation was measured using
osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was
measured using serum type 1 collage c-telopeptide. The effect of control and IBD
patient sera on human osteoblast viability and differentiation was analysed.
RESULTS: OC level was higher in controls than IBD patients (P=0.018). After IFX,
OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011)
and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There
was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX
therapy, proinflammatory cytokines TNF-alpha, interleukin-6 and interleukin-13
decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6),
respectively. Sera from IBD patients before IFX showed increased osteoblast
viability compared with the controls (P=0.003 to P<0.005), but induced reduced
osteoblast differentiation. After IFX, viability reduced to control levels, but
osteoblast differentiation increased (P=0.041). CONCLUSION: IFX treatment induced
beneficial effects on bone metabolism. Osteoblast culture results suggest that
IBD patients may have increased osteoblast viability, but reduced
differentiation, which has implications for bone strength.
PMID- 27508328
TI - Laparoscopic Approach for Thermoablation Microwave in the Treatment of
Hepatocellular Carcinoma: A Single Center Experience.
AB - BACKGROUND: The surgical therapy of choice for hepatocellular carcinoma (HCC) is
liver transplantation (LT) or hepatic resection, although only a small percentage
of patients can undergo these procedures. Microwave thermal ablation (MWTA) can
be an effective alternative treatment for HCC that complicates a cirrhotic liver
disease, either as a final procedure or for downstaging patients on the waiting
list for LT, or in combination with resective surgery to achieve oncological
radicality. OBJECTIVE: The purpose of this retrospective study was to evaluate
experience with the laparoscopic approach of MWTA at our center. MATERIALS AND
METHODS: In a cohort of 35 consecutive patients undergoing MWTA with laparoscopic
approach between January, 2013 and May, 2016, we reviewed the demographic data,
the Barcelona clinic liver cancer stage, the severity of cirrhotic liver disease,
the size of the ablated lesion, the duration of the procedure, and complications
occurring within 90 days of surgery. RESULTS: MWTA was performed by applying one
to three hepatic parenchymal insertions (mean 1.8) per patient. The mean duration
of surgery was 163 +/- 18 minutes. There was no blood loss in any of the
procedures. Complete necrosis on CT scan was achieved in 26/35 patients (75%).
The mean hospital stay was 4.6 (range 2-7) days; major complications were
postablation syndrome in 2/35 (5.7%), peritoneal fluid in 4/35 (11.4%), and
transient jaundice in 1/35 (2.8%) patients. There was no mortality. CONCLUSIONS:
Laparoscopic MTWA is a safe and effective treatment for unresectable HCC and when
a percutaneous procedure is not feasible.
PMID- 27508329
TI - Connection Map for Compounds (CMC): A Server for Combinatorial Drug Toxicity and
Efficacy Analysis.
AB - Drug discovery and development is a costly and time-consuming process with a high
risk for failure resulting primarily from a drug's associated clinical safety and
efficacy potential. Identifying and eliminating inapt candidate drugs as early as
possible is an effective way for reducing unnecessary costs, but limited
analytical tools are currently available for this purpose. Recent growth in the
area of toxicogenomics and pharmacogenomics has provided with a vast amount of
drug expression microarray data. Web servers such as CMap and LTMap have used
this information to evaluate drug toxicity and mechanisms of action
independently; however, their wider applicability has been limited by the lack of
a combinatorial drug-safety type of analysis. Using available genome-wide drug
transcriptional expression profiles, we developed the first web server for
combinatorial evaluation of toxicity and efficacy of candidate drugs named
"Connection Map for Compounds" (CMC). Using CMC, researchers can initially
compare their query drug gene signatures with prebuilt gene profiles generated
from two large-scale toxicogenomics databases, and subsequently perform a drug
efficacy analysis for identification of known mechanisms of drug action or
generation of new predictions. CMC provides a novel approach for drug
repositioning and early evaluation in drug discovery with its unique combination
of toxicity and efficacy analyses, expansibility of data and algorithms, and
customization of reference gene profiles. CMC can be freely accessed at
http://cadd.tongji.edu.cn/webserver/CMCbp.jsp .
PMID- 27508330
TI - Efficient Cellular Knockdown Mediated by siRNA Nanovectors of Gemini Cationic
Lipids Having Delocalizable Headgroups and Oligo-Oxyethylene Spacers.
AB - The use of small interfering RNAs (siRNAs) to silence specific genes is one of
the most promising approaches in gene therapy, but it requires efficient
nanovectors for successful cellular delivery. Recently, we reported liposomal
gene carriers derived from a gemini cationic lipid (GCL) of the 1,2-bis(hexadecyl
dimethyl imidazolium) oligo-oxyethylene series ((C16Im)2(C2H4O)nC2H4 with n = 1,
2, or 3) and 1,2-dioleyol phosphatidylethanolamine as highly efficient
cytofectins for pDNA. On the basis of the satisfactory outcomes of the previous
study, the present work focuses on the utility of coliposomes of these gemini
lipids with the biocompatible neutral lipid mono oleoyl glycerol (MOG) as highly
potent vectors for siRNA cellular transport in the presence of serum. The
(C16Im)2(C2H4O)nC2H4/MOG-siRNA lipoplexes were characterized through (i) a
physicochemical study (zeta potential, cryo-transmission electron microscopy,
small-angle X-ray scattering, and fluorescence anisotropy) to establish the
relationship between size, structure, fluidity, and the interaction between siRNA
and the GCL/MOG gene vectors and (ii) a biological analysis (flow cytometry,
fluorescence microscopy, and cell viability) to report the anti-GFP siRNA
transfections in HEK 293T, HeLa, and H1299 cancer cell lines. The in vitro
biological analysis confirms the cellular uptake and indicates that a short
spacer, a very low molar fraction of GCL in the mixed lipid, and a moderate
effective charge ratio of the lipoplex yielded maximum silencing efficacy. At
these experimental conditions, the siRNA used in this work is compacted by the
GCL/MOG nanovectors by forming two cubic structures (Ia3d and Pm3n) that are
correlated with excellent silencing activity. These liposomal nanocarriers
possess high silencing activity with a negligible cytotoxicity, which strongly
supports their practical use for in vivo knockdown studies.
PMID- 27508331
TI - Adaptation to an invasive host is driving the loss of a native ecotype.
AB - Locally adapted populations are often used as model systems for the early stages
of ecological speciation, but most of these young divergent populations will
never become complete species. The maintenance of local adaptation relies on the
strength of natural selection overwhelming the homogenizing effects of gene flow;
however, this balance may be readily upset in changing environments. Here I show
that soapberry bugs (Jadera haematoloma) have lost adaptations to their native
host plant (Cardiospermum corindum) and are regionally specializing on an
invasive host (Koelreuteria elegans), collapsing a classic and well-documented
example of local adaptation. All populations that were adapted to the native host
including those still found on that host today-are now better adapted to the
invasive host in multiple phenotypes. Weak differentiation remains in two traits,
suggesting that homogenization across the region is incomplete. This study
highlights the potential for adaptation to invasive species to disrupt native
communities by swamping adaptation to native conditions through maladaptive gene
flow.
PMID- 27508332
TI - Nonpuerperal Mastitis Acts as the Initial Presentation of Pituitary Prolactinoma.
PMID- 27508333
TI - In vivo assessment of a new multifunctional coating architecture for improved Mg
alloy biocompatibility.
AB - Magnesium alloys are regarded as potential biodegradable load-bearing
biomaterials for orthopedic applications due to their physico-chemical and
biomechanical properties. However, their clinical applicability is restricted by
their high degradation rate, which limits the physiological reconstruction of the
neighbouring tissues. In this work, a multifunctional coating architecture was
developed on an AZ31 alloy by conjoining an anodization process with the
deposition of a polymeric-based layer consisting of polyether imine reinforced
with hydroxyapatite nanoparticles, aiming at improved control of the corrosion
activity and biological performance of the Mg substrate. Anodization and coating
protocols were evaluated either independently or combined for corrosion
resistance and biological behaviour, i.e. the irritation potential and angiogenic
capability within a chicken chorioallantoic membrane assay, and bone tissue
response following tibia implantation within a rabbit model. Electrochemical
impedance spectroscopy (EIS) analysis showed that coated Mg constructs,
particularly anodized plus coated with AZ31, exhibited excellent stability
compared to the anodized alloy and, particularly, to the bare AZ31.
Microtomographic evaluation of the implanted samples correlated with these
degradation results. Mg constructs displayed a non-irritating behaviour, and were
associated with high levels of vascular ingrowth. Bone ingrowth neighbouring the
implanted constructs was observed for all samples, with coated and anodized plus
coated samples presenting the highest bone formation. Gene expression analysis
suggested that the enhanced bone tissue formation was associated with the boost
in osteogenic activity through Runx2 upregulation, following the activation of
PGC-1alpha/ERRalpha signaling. Overall, the developed multifunctional coatings
appear to be a promising strategy to obtain safe and bioactive biodegradable Mg
based implants with potential applications within bone tissue.
PMID- 27508334
TI - Surgical Hand Antisepsis and Surgical Site Infections.
AB - BACKGROUND: Surgical site infections (SSI) remain a significant problem to both
the patients and the healthcare system. Value care and standardized quality
measures continue to promote improvement in surgical asepsis, but certain debates
remain unresolved in the field of surgical hand antisepsis. METHODS: Review of
relevant accounts and literature. RESULTS: Controversy has existed regarding the
U.S. Food and Drug Administration (FDA)'s 1994 Tentative Final Monograph (TFM),
which defined how surgical hand antisepsis products are assessed. Issues
involving neutralizers and demonstration of a cumulative effect were addressed in
the FDA's Proposed Rule in 2015. Few studies have used SSI as a primary outcome
and instead have used a surrogate marker (colony-forming units [CFU]).
Quantitative microbiology studies suggest a minimum bacterial inoculum of 105-107
CFU/mL is necessary to cause a clinical infection. Outcomes of antisepsis likely
are driven by both active ingredient(s) and overall product formulation. Povidone
iodine aqueous scrubs are inferior to chlorhexidine gluconate (CHG) 4% aqueous
scrubs and alcohol-based rubs (ABR). The SSI and CFU outcomes studies support the
equivalence or superiority of ABR over CHG. CONCLUSIONS: Both ABRs and CHG 4% are
preferred to povidone-iodine for surgical hand antisepsis. Well-powered
randomized controlled trials measuring SSI as a primary outcome, as well as those
designed according to either TFM or European methodology, with appropriate
controls and neutralizers, are warranted. These trials should incorporate
different ABR formulations and CHG 4%, as well as skin tolerance assessments and
a cost analysis.
PMID- 27508335
TI - Effects of Manganese Oxide on Arsenic Reduction and Leaching from Contaminated
Floodplain Soil.
AB - Reductive release of the potentially toxic metalloid As from Fe(III)
(oxyhydr)oxides has been identified as an important process leading to elevated
As porewater concentrations in soils and sediments. Despite the ubiquitous
presence of Mn oxides in soils and their oxidizing power toward As(III), their
impact on interrelated As, Fe, and Mn speciation under microbially reducing
conditions remains largely unknown. For this reason, we employed a column setup
and X-ray absorption spectroscopy to investigate the influence of increasing
birnessite concentrations (molar soil Fe-to-Mn ratios: 4.8, 10.2, and 24.7) on As
speciation and release from an As-contaminated floodplain soil (214 mg As/kg)
under anoxic conditions. Our results show that birnessite additions significantly
decreased As leaching. The reduction of both As and Fe was delayed, and As(III)
accumulated in birnessite-rich column parts, indicating the passivation of
birnessite and its transformation products toward As(III) oxidation and the
precipitation of Fe(III)(oxyhydr)oxides. Microbial Mn reduction resulted in
elevated soil pH values, which in turn lowered the microbial activity in the
birnessite-enriched soil. We conclude that in Mn-oxide-rich soil environments
undergoing redox fluctuations, the enhanced As adsorption to newly formed Fe(III)
(oxyhydr)oxides under reducing conditions leads to a transient stabilization of
As.
PMID- 27508336
TI - Reports to FDA of fatal anaphylaxis associated with intravenous iron products.
PMID- 27508338
TI - Use of CT to evaluate and compare intranasal features in brachycephalic and
normocephalic dogs.
AB - OBJECTIVES: To evaluate and compare nasal mucosal contact, septal deviation and
caudal aberrant nasal turbinates in brachycephalic and normocephalic dogs using
computed tomography. METHODS: Dogs without nasal disease and having undergone
computed tomography scan of the head (plica alaris to the cribiform plate) were
retrospectively selected and divided into brachycephalic and normocephalic
groups. Eighteen brachycephalic and 32 normocephalic dogs were included. Anatomic
criteria were used to locate predetermined pairs of intranasal structures and
nasal mucosal contact was described as present or absent for each site. Septal
deviations were identified and measured using angle of septal deviation. Caudal
aberrant nasal turbinates were identified and categorised when present. RESULTS:
Prevalence of nasal mucosal contact was significantly higher in brachycephalic
dogs. No significant difference was seen in prevalence or in angle of septal
deviation between groups. Prevalence of caudal aberrant nasal turbinates was
significantly higher in brachycephalic dogs. CLINICAL SIGNIFICANCE: Nasal mucosal
contact and caudal aberrant nasal turbinates were significantly more prevalent in
brachycephalic dogs than in normocephalic dogs in our study. Computed tomography
can be a valuable aid in obtaining data on nasal mucosal contact, caudal aberrant
nasal turbinates and septal deviations. Combination of computed tomography with
endoscopy and functional airway testing would be useful to further evaluate the
correlation between intranasal features and symptoms of brachycephalic airway
syndrome.
PMID- 27508339
TI - Tailored Nanoparticle Codelivery of antimiR-21 and antimiR-10b Augments
Glioblastoma Cell Kill by Temozolomide: Toward a "Personalized" Anti-microRNA
Therapy.
AB - Glioblastoma remains an aggressive brain malignancy with poor prognosis despite
advances in multimodal therapy that include standard use of Temozolomide.
MicroRNA-21 (miR-21) and microRNA-10b (miR-10b) are oncomiRs overexpressed in
glioblastoma, promoting many aspects of cancer biology. We hypothesized that PLGA
nanoparticles carrying antisense miR-21 (antimiR-21) and antisense miR-10b
(antimiR-10b) might beneficially knockdown endogenous miR-21 and miR-10b function
and reprogram cells prior to Temozolomide treatment. PLGA nanoparticles were
effective in intracellular delivery of encapsulated oligonucleotides.
Concentrations of delivered antimiR-21 and antimiR-10b were optimized and
specifically tailored to copy numbers of intracellular endogenous microRNAs.
Coinhibition of miR-21 and miR-10b significantly reduced the number of viable
cells (by 24%; p < 0.01) and increased (2.9-fold) cell cycle arrest at G2/M phase
upon Temozolomide treatment in U87 MG cells. Cell-tailored nanoparticle-assisted
concurrent silencing of miR-21 and miR-10b prior to Temozolomide treatment is an
effective molecular therapeutic strategy in cell culture, warranting the need for
further studies prior to future in vivo "personalized" medicine applications.
PMID- 27508341
TI - The Pitt Innovation Challenge (PInCh): Driving Innovation in Translational
Research Through an Incentive-Based, Problem-Focused Competition.
AB - PROBLEM: Translational research aims to move scientific discoveries across the
biomedical spectrum from the laboratory to humans, and to ultimately transform
clinical practice and public health policies. Despite efforts to accelerate
translational research through national initiatives, several major hurdles
remain. APPROACH: The authors created the Pitt Innovation Challenge (PInCh) as an
incentive-based, problem-focused approach to solving identified clinical or
public health problems at the University of Pittsburgh Clinical and Translational
Science Institute in spring 2014. With input from a broad range of stakeholders,
PInCh leadership arrived at the challenge question: How do we empower individuals
to take control of their own health outcomes? The authors developed the PInCh's
three-round proposal submission and review process as well as an online contest
management tool to support the process. OUTCOMES: Ninety-two teams submitted
video proposals in round one. Proposals included mobile applications (29; 32%),
other information technology (19; 21%), and community program (22; 24%)
solutions. Ten teams advanced to the final round, where three were awarded
$100,000 to implement their solution over 12 months. In a 6-month follow-up
survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections
outside their normal sphere of collaborators. NEXT STEPS: Additional educational
training sessions related to problem-focused research will be developed. The
PInCh will be expanded to engage investment and industry communities to
facilitate the translation of solutions to clinical practice via
commercialization pathways. External organizations and other universities will be
engaged to use the PInCh as a mechanism to fuel innovation in their spaces.
PMID- 27508337
TI - Early adverse experience and substance addiction: dopamine, oxytocin, and
glucocorticoid pathways.
AB - Substance addiction may follow a chronic, relapsing course and critically
undermine the physical and psychological well-being of the affected individual
and the social units of which the individual is a member. Despite the public
health burden associated with substance addiction, treatment options remain
suboptimal, with relapses often seen. The present review synthesizes growing
insights from animal and human research to shed light upon developmental and
neurobiological pathways that may increase susceptibility to addiction. We
examine the dopamine system, the oxytocin system, and the glucocorticoid system,
as they are particularly relevant to substance addiction. Our aim is to delineate
how early adverse experience may induce long-lasting alterations in each of these
systems at molecular, neuroendocrine, and behavioral levels and ultimately lead
to heightened vulnerability to substance addiction. We further discuss how
substance addiction in adulthood may increase the risk of suboptimal caregiving
for the next generation, perpetuating the intergenerational cycle of early
adverse experiences and addiction.
PMID- 27508340
TI - Quantitative proteomics of rat livers shows that unrestricted feeding is
stressful for proteostasis with implications on life span.
AB - Studies in young mammals on the molecular effects of food restriction leading to
prolong adult life are scares. Here, we used high-throughput quantitative
proteomic analysis of whole rat livers to address the molecular basis for growth
arrest and the apparent life-prolonging phenotype of the food restriction
regimen. Over 1800 common proteins were significantly quantified in livers of ad
libitum, restriction- and re-fed rats, which summed up into 92% of the total
protein mass of the cells. Compared to restriction, ad libitum cells contained
significantly less mitochondrial catabolic enzymes and more cytosolic and ER
HSP90 and HSP70 chaperones, which are hallmarks of heat- and chemically-stressed
tissues. Following re-feeding, levels of HSPs nearly reached ad libitum levels.
The quantitative and qualitative protein values indicated that the restriction
regimen was a least stressful condition that used minimal amounts of HSP
chaperones to maintain optimal protein homeostasis and sustain optimal life span.
In contrast, the elevated levels of HSP-chaperones in ad libitum tissues were
characteristic of a chronic stress, which in the long term could lead to early
aging and shorter life span.
PMID- 27508342
TI - The Community Mentorship Program: Providing Community-Engagement Opportunities
for Early-Stage Clinical and Translational Scientists to Facilitate Research
Translation.
AB - PROBLEM: A goal of the Southern California Clinical and Translational Science
Institute (SC-CTSI) at the University of Southern California and Children's
Hospital Los Angeles is to train early-stage clinical and translational
scientists (CTSs) to conduct research that improves the health of diverse
communities. This goal aligns well with the Institute of Medicine's
recommendations emphasizing community engagement in biomedical research that
facilitates research translation. The Community Mentorship Program (CMP), created
to complement community-engaged research didactics, matches CTSs with community
mentors who help them identify and complete community-engaged experiences that
inform their research. APPROACH: The CMP was piloted in 2013-2015 by the SC-CTSI
Workforce Development and Community Engagement cores. The CMP team matched three
CTSs (assistant professors pursuing mentored career development awards) with
mentors at community-based organizations (CBOs) aligned with their research
interests. Each mentor-mentee pair signed a memorandum of understanding. The CMP
team checked in regularly, monitoring progress and addressing challenges in CTSs'
completion of their community-engaged experience. OUTCOMES: Each pair completed
at least one community-engaged activity informing the CTS's research. In exit
interviews, the CTSs and CBO mentors expressed satisfaction with the program and
stated that they would continue to work together. The CTSs reported that the
program provided opportunities to develop networks outside academia, build trust
within the community, and receive feedback and learn from individuals in
communities affected by their research. NEXT STEPS: The CMP will be expanded to
include all eligible early-career CTSs and promoted for use in similar settings
outside the SC-CTSI.
PMID- 27508344
TI - Internationally Educated Health Professionals in Canada: Navigating Three Policy
Subsystems Along the Pathway to Practice.
AB - The integration of internationally educated health professionals (IEHPs) into the
health workforces of their adopted countries is an issue that has challenged
policy makers and policy scholars for decades. In this article, the authors
explore the implications of the ideological underpinnings of the policy
subsystems that IEHPs must navigate in seeking employment in Canada, with a focus
on Ontario.Using a policy subsystem approach, in 2015 the authors analyzed a
large preexisting data set composed of articles, governmental reports, Web sites,
and transcripts of interviews and focus groups conducted in Ontario with IEHPs,
health care executives, human resource managers, and job counselors to IEHPs.
Through this analysis, they identified three policy subsystems-the immigration
system, the educational and licensure/regulatory system, and the health human
resources system-that conflict ideologically and, as a result, create barriers to
IEHP integration.To make substantive progress on IEHP integration in Canada, four
questions should be considered. First, how can researchers bring new research
methods to bear to explore why no jurisdiction has been able to create an
integrated pathway to practice for IEHPs? Second, how and to what end are the
institutions within the three policy subsystems regulating the IEHP pathway to
practice? Third, how might the educational and licensure/regulatory policy
subsystem create alternative health care employment options for IEHPs? Finally,
how might health professions educators pursue a leadership role in the creation
of an overarching institution to manage the pathway to practice for IEHPs?
PMID- 27508343
TI - Population Health Science: A Core Element of Health Science Education in Sub
Saharan Africa.
AB - Sub-Saharan Africa suffers an inordinate burden of disease and does not have the
numbers of suitably trained health care workers to address this challenge. New
concepts in health sciences education are needed to offer alternatives to current
training approaches.A perspective of integrated training in population health for
undergraduate medical and nursing education is advanced, rather than continuing
to take separate approaches for clinical and public health education. Population
health science educates students in the social and environmental origins of
disease, thus complementing disease-specific training and providing opportunities
for learners to take the perspective of the community as a critical part of their
education.Many of the recent initiatives in health science education in sub
Saharan Africa are reviewed, and two case studies of innovative change in
undergraduate medical education are presented that begin to incorporate such
population health thinking. The focus is on East Africa, one of the most rapidly
growing economies in sub-Saharan Africa where opportunities for change in health
science education are opening. The authors conclude that a focus on population
health is a timely and effective way for enhancing training of health care
professionals to reduce the burden of disease in sub-Saharan Africa.
PMID- 27508345
TI - Hyperglycemia is associated with increased risk of patient delay in pulmonary
tuberculosis in rural areas.
AB - BACKGROUND: Excessive time between the first presentation of symptoms of
pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission
and increased risk of infection in the community, as well as to increased disease
severity and higher mortality. People with type 2 diabetes mellitus (T2DM) have a
higher risk of developing PTB. However, the effect of T2DM on delayed diagnosis
of PTB is not fully understood. This study investigated the effects of
hyperglycemia (diabetes and prediabetes) and other factors on PTB patient delay
in a rural area of China. METHODS: In the present community-based investigation,
PTB patients aged >=16 years newly diagnosed at county tuberculosis dispensaries
were recruited consecutively between September 2011 and December 2013. Fasting
blood glucose was determined in all subjects, and a structured questionnaire was
used to collect basic information. RESULTS: Of the 2280 patients, 605 (26.5 %)
had hyperglycemia. The median (interquartile range) time to seeking health care
was 44 (59) days. Health care seeking was delayed in 1754 subjects, and
hyperglycemia was independently associated with an increased probability (odds
ratio 2.10; 95 % confidence interval 1.49-2.97) of patient delay in subjects aged
>=30 years. Other factors associated with patient delay were cough, night sweats,
and lack of knowledge regarding typical tuberculosis symptoms. The onset of
hemoptysis was negatively correlated with patient delay. CONCLUSIONS: Patient
delay appears to be a serious problem in this rural area with a high prevalence
of tuberculosis. Hyperglycemia is independently associated with an increased
probability of patient delay, which, in turn, may result in more serious clinical
manifestations.
PMID- 27508347
TI - Ultrafast Hole Transfer from (6,5) SWCNT to P3HT:PCBM Blend by Resonant
Excitation.
AB - Nowadays, SWCNTs are envisaged to enhance the charge separation or transport of
conjugated polymer-fullerene derivatives blends. In this work we studied, by
means of ultrafast transient absorption spectroscopy, three components blends in
which commercially available SWCNTs are added to the standard bulk
heterojunction. We explored three different configurations that give rise to
diverse interfacing scenarios. We found strong evidence of a direct hole transfer
from photoexcited SWCNTs to the P3HT polymer. The transfer efficiency depends on
the interface configuration. It is the highest for the blend where we achieve
closer contact between the (6,5) SWCNTs and the polymer. When the polymer blend
is deposited on top of the nanotube film or the nanotube film is deposited onto
the polymer blend, the process is slowed down due to less or missing interfacing
of the carbon nanotubes with the polymer chains. Additionally we demonstrate a
cascading effect in the electron path, which stabilizes charge separation by
further transferring the electron left behind by hole transfer to the polymer to
the adjacent (7,5) SWCNTs. Our results highlight the potential of semiconducting
SWCNTs to improving the performance of organic solar cells.
PMID- 27508346
TI - Unidirectional and sustained delivery of the proresolving lipid mediator resolvin
D1 from a biodegradable thin film device.
AB - Resolvin D1 (RvD1) belongs to a family of endogenously derived proresolving lipid
mediators that have been shown to attenuate inflammation, activate proresolution
signaling, and promote homeostasis and recovery from tissue injury. In this study
we present a poly(lactic-co-glycolic acid) (PLGA) based thin-film device composed
of layers of varying ratios of lactic and glycolic acid that elutes RvD1
unidirectionally to target tissues. The device demonstrated sustained release in
vitro for 56 days with an initial burst of release over 14 days. The asymmetric
design of the device released 98% of RvD1 through the layer with the lowest molar
ratio of lactic acid to glycolic acid, and the remainder through the opposite
side. We validated structural integrity of RvD1 released from the device by mass
spectrometry and investigated its bioactivity on human vascular endothelial (EC)
and smooth muscle cells (VSMC). RvD1 released from the device attenuated VSMC
migration, proliferation, and TNF-alpha induced NF-kappaB activation, without
evidence of cytotoxicity. Delivery of RvD1 to blood vessels was demonstrated ex
vivo in a flow chamber system using perfused rabbit aortas and in vivo in a rat
carotid artery model, with the devices applied as an adventitial wrap. Our
results demonstrate a novel approach for sustained, local delivery of Resolvin D1
to vascular tissue at therapeutically relevant levels. (c) 2016 Wiley
Periodicals, Inc. J Biomed Mater Res Part A: 105A: 31-41, 2017.
PMID- 27508348
TI - Drugs for bipolar disorder.
PMID- 27508349
TI - Sofosbuvir/velpatasvir (Epclusa) for hepatitis C.
PMID- 27508350
TI - Criteria for designation of clinical substage in canine lymphoma: a survey of
veterinary oncologists.
AB - Clinical substage is frequently reported to be prognostic in dogs with lymphoma,
yet formal criteria for defining this parameter are lacking. The World Health
Organization TNM Classification of Tumors of Domestic Animals simply defines
substage as the absence or presence of systemic signs (substages a and b,
respectively). We designed a survey to query veterinary oncologists on the
criteria they use to determine clinical substage in practice. Gastrointestinal,
constitutional and respiratory signs were the most commonly identified clinical
factors, with greater than 90% respondents indicating that inappetence, vomiting,
diarrhoea, changes in attitude, weakness and dyspnea were integral in assigning
clinical substage. Nevertheless, more than three-quarters of respondents also
considered metabolic, neurologic and nutritional parameters when making this
determination. For most factors, respondents reported mild-to-moderate severity
of clinical signs was sufficient for substage b designation.
PMID- 27508352
TI - Retraction Notice.
AB - [This retracts the article on p. 65 in vol. 7, PMID: 26435620.].
PMID- 27508353
TI - Prehospital Application of the Canadian Triage and Acuity Scale by Emergency
Medical Services.
AB - OBJECTIVES: Triage is fundamental to emergency patient assessment. Effective
triage systems accurately prioritize patients and help predict resource
utilization. CTAS is a validated five-level triage score utilized in Emergency
Departments (EDs) across Canada and internationally. Historically CTAS has been
applied by triage nurses in EDs. Observational evidence suggests that the CTAS
might be implemented reliably by paramedics in the prehospital setting. This is
the first system-wide assessment of CTAS interrater reliability between
paramedics and triage nurses during clinical practice. METHODS: Variables were
extracted from hospital and EMS databases. EMS providers determined CTAS on
scene, CTAS pre-transport, and CTAS on-arrival at hospital for each patient
(N=14,378). The hospital arrival EMS CTAS (CTAS arrival ) score was compared to
the initial nursing CTAS score (CTAS initial ) and the final nursing CTAS score
(CTAS final ) incuding nursing overrides. Interrater reliability between ED CTAS
initial and EMS CTAS arrival scores was assessed. Interrater reliability between
ED CTAS final and EMS CTAS arrival scores, as well as proportion of patient
encounters with perfect or near-perfect agreement, were evaluated. RESULTS: Our
primary outcome, interrater reliability [kappa=0.437 (p<0.001, 95% CI 0.421
0.452)], indicated moderate agreement. EMS CTAS arrival and ED CTAS initial
scores had an exact or within one point match 84.3% of the time. The secondary
interrater reliability outcome between hospital arrival EMS CTAS (CTAS arrival )
score and the final ED triage CTAS score (CTAS final ) showed moderate agreement
with kappa =0.452 (p<0.001, 95% CI 0.437-0.466). CONCLUSIONS: Interrater
reliability of CTAS scoring between triage nurses and paramedics was moderate in
this system-wide implementation study.
PMID- 27508351
TI - White adipose tissue inflammation and cancer-specific survival in patients with
squamous cell carcinoma of the oral tongue.
AB - BACKGROUND: Obesity is associated with increased adipose tissue in the tongue.
Chronic white adipose tissue (WAT) inflammation commonly occurs in the obese. We
investigated whether WAT inflammation in the tongue impacts survival in patients
with squamous cell carcinoma (SCC) of the oral tongue. METHODS: In a
retrospective cohort study, patients with T1 and T2 SCC of the oral tongue who
underwent curative-intent resection were included. Tongue WAT inflammation was
defined by the presence of dead or dying adipocytes surrounded by macrophages
forming crown-like structures. The primary and secondary endpoints were disease
specific survival (DSS) and overall survival (OS), respectively. Subgroup
analyses were carried out in patients without lymph node involvement for whom
adjuvant therapies were not indicated. RESULTS: Archived tissue was available
from 125 patients. The median follow-up was 55 months (range, 3-156 months).
Overall, 49 of 125 patients (39%) had tongue WAT inflammation, which was
associated with higher body mass index, increased tumor thickness, and vascular
invasion (P < .05). The 3-year DSS rate for patients with tongue WAT inflammation
was 59% (95% confidence interval [CI], 46%-76%) versus 82% (95% CI, 73%-92%) for
those without inflammation. For patients without lymph node involvement for whom
adjuvant therapy was not indicated (N = 70), tongue WAT inflammation was
associated with shortened DSS and OS (P < .05). When adjusted for body mass index
and potential prognostic covariates, the hazard ratio for DSS and OS was 5.40
(95% CI, 1.20-24.26) and 2.97 (95% CI, 1.02-8.65), respectively. CONCLUSIONS:
Tongue WAT inflammation is associated with worse DSS and OS in patients who have
early stage SCC of the oral tongue. Cancer 2016;122:3794-3802. (c) 2016 American
Cancer Society.
PMID- 27508354
TI - Rhizobial strains exert a major effect on the amino acid composition of alfalfa
nodules under NaCl stress.
AB - Specific amino acids have protective functions in plants under stress conditions.
This study assessed the effects of rhizobial strains on the amino acid
composition in alfalfa under salt stress. Two alfalfa cultivars (Medicago sativa
L. cv Apica and salt-tolerant cv Halo) in association with two Sinorhizobium
meliloti strains with contrasting growth under salt stress (strain A2 and salt
tolerant strain Rm1521) were exposed to different levels of NaCl (0, 20, 40, 80
or 160 mM NaCl) under controlled conditions. We compared root and shoot
biomasses, as well as root:shoot ratio for each association under these
conditions as indicators of the salt tolerance of the symbiosis. Amino acid
concentrations were analyzed in nodules, leaves and roots. The total
concentration of free amino acids in nodules was mostly rhizobial-strain
dependent while in leaves and roots it was mostly responsive to salt stress. For
both cultivars, total and individual concentrations of amino acids including
asparagine, proline, glutamine, aspartate, glutamate, gamma-aminobutyric acid
(GABA), histidine and ornithine were higher in Rm1521 nodules than in A2 nodules.
Conversely, lysine and methionine were more abundant in A2 nodules than in Rm1521
nodules. Proline, glutamine, arginine, GABA and histidine substantially
accumulated in salt-stressed nodules, suggesting an enhanced production of amino
acids associated with osmoregulation, N storage or energy metabolism to
counteract salt stress. Combining the salt-tolerant strain Rm1521 and the salt
tolerant cultivar Halo enhanced the root:shoot ratios and amino acid
concentrations involved in plant protection which could be in part responsible
for the enhancement of salt tolerance in alfalfa.
PMID- 27508356
TI - LC-MS/MS analysis of metformin, saxagliptin and 5-hydroxy saxagliptin in human
plasma and its pharmacokinetic study with a fixed-dose formulation in healthy
Indian subjects.
AB - A specific and rapid liquid chromatography-tandem mass spectrometry method is
proposed for the simultaneous determination of metformin (MET), saxagliptin
(SAXA) and its active metabolite, 5-hydroxy saxagliptin (5-OH SAXA) in human
plasma. Sample preparation was accomplished from 50 MUL plasma sample by solid
phase extraction using sodium dodecyl sulfate as an ion-pair reagent. Reversed
phase chromatographic resolution of analytes was possible within 3.5 min on ACE
5CN (150 * 4.6 mm, 5 MUm) column using acetonitrile and10.0 mm ammonium formate
buffer, pH 5.0 (80:20, v/v) as the mobile phase. Triple quadrupole mass
spectrometric detection was performed using electrospray ionization in the
positive ionization mode. The calibration curves showed good linearity (r2 >=
0.9992) over the established concentration range with limit of quantification of
1.50, 0.10 and 0.20 ng/mL for MET, SAXA and 5-OH SAXA respectively. The
extraction recoveries obtained from spiked plasma samples were highly consistent
for MET (75.12-77.84%), SAXA (85.90-87.84%) and 5-OH SAXA (80.32-82.69%) across
quality controls. The validated method was successfully applied to a
bioequivalence study with a fixed-dose formulation consisting of 5 mg SAXA and
500 mg MET in 18 healthy subjects. The reproducibility of the assay was
demonstrated by reanalysis of 87 incurred samples.
PMID- 27508355
TI - Hippocampal pattern completion is linked to gamma power increases and alpha power
decreases during recollection.
AB - How do we retrieve vivid memories upon encountering a simple cue? Computational
models suggest that this feat is accomplished by pattern completion processes
involving the hippocampus. However, empirical evidence for hippocampal pattern
completion and its underlying mechanisms has remained elusive. Here, we recorded
direct intracranial EEG as human participants performed an associative memory
task. For each study (encoding) and test (retrieval) event, we derived time
frequency resolved representational patterns in the hippocampus and compared the
extent of pattern reinstatement for different mnemonic outcomes. Results show
that successful associative recognition (AR) yields enhanced event-specific
reinstatement of encoding patterns compared to non-associative item recognition
(IR). Moreover, we found that gamma power (50-90 Hz) increases - in conjunction
with alpha power (8-12 Hz) decreases not only distinguish AR from IR, but also
correlate with the level of hippocampal reinstatement. These results link single
shot hippocampal pattern completion to episodic recollection and reveal how
oscillatory dynamics in the gamma and alpha bands orchestrate these mnemonic
processes.
PMID- 27508357
TI - Ultrafine TiO2 Decorated Carbon Nanofibers as Multifunctional Interlayer for High
Performance Lithium-Sulfur Battery.
AB - Although lithium-sulfur (Li-S) batteries deliver high specific energy densities,
lots of intrinsic and fatal obstacles still restrict their practical application.
Electrospun carbon nanofibers (CNFs) decorated with ultrafine TiO2 nanoparticles
(CNF-T) were prepared and used as a multifunctional interlayer to suppress the
volume expansion and shuttle effect of Li-S battery. With this strategy, the CNF
network with abundant space and superior conductivity can accommodate and recycle
the dissolved polysulfides for the bare sulfur cathode. Meanwhile, the ultrafine
TiO2 nanoparticles on CNFs work as anchoring points to capture the polysulfides
with the strong interaction, making the battery perform with remarkable and
stable electrochemical properties. As a result, the Li-S battery with the CNF-T
interlayer delivers an initial reversible capacity of 935 mA h g(-1) at 1 C with
a capacity retention of 74.2% after 500 cycles. It is believed that this simple,
low-cost and scalable method will definitely bring a novel perspective on the
practical utilization of Li-S batteries.
PMID- 27508358
TI - Cycled light in the intensive care unit for preterm and low birth weight infants.
AB - BACKGROUND: Potential benefits and harms of different lighting in neonatal units
have not been quantified. OBJECTIVES: * To determine effectiveness and safety of
cycled light (CL) (approximately 12 hours of light on and 12 hours of light off)
for growth in preterm infants at three and six months' corrected age (CA).* In
separate analyses, to compare effects of CL with those of irregularly dimmed
light (DL) or near darkness (ND), and effects of CL with those of continuous
bright light (CBL), on growth in preterm infants at three and six months' CA.* To
assess, in subgroup analyses, the effectiveness and safety of CL (vs control
interventions (DL, ND and CBL)) introduced at different postmenstrual ages (PMAs)
- before 32 weeks', at 32 weeks' and from 36 weeks' PMA - and to compare
effectiveness and safety of CL for small for gestational age (GA) infants versus
appropriately grown 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 12), MEDLINE via PubMed (1966 to January
2016), Embase (1980 to January 2016) and the Cumulative Index to Nursing and
Allied Health Literature (CINAHL; 1982 to January 2016). We searched clinical
trials databases, conference proceedings and reference lists of retrieved
articles for randomised controlled trials and quasi-randomised trials. SELECTION
CRITERIA: Randomised or quasi-randomised trials of CL versus ND or CBL in preterm
and low birth weight infants. DATA COLLECTION AND ANALYSIS: We performed data
collection and analyses according to the methods of the Cochrane Neonatal Review
Group. We used the Grading of Recommendations Assessment, Development and
Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: We
identified one additional study enrolling 38 participants for inclusion in this
update, for a total of nine studies reporting on 544 infants. In general, the
quality of the studies was low, mainly owing to lack of blinding and small sample
sizes.Six studies enrolling 424 infants compared CL versus ND. No study reported
on weight at three or six months. One study (n = 40) found no statistically
significant difference in weight at four months between CL and ND groups. In
another study (n = 62), the ratio of day-night activity before discharge favoured
the CL group (mean difference (MD) 0.18, 95% confidence interval (CI) 0.17 to
0.19), indicating 18% more activity during the day than during the night in the
CL group compared with the ND group. Two studies (n = 189) reported on
retinopathy of prematurity (stage >= 3) and reported no statistically significant
differences between CL and ND groups (typical risk ratio (RR) 0.53, 95% CI 0.25
to 1.11, I(2) = 0%; typical risk difference (RD) -0.09, 95% CI -0.19 to 0.01,
I(2) = 0%). Two studies (n = 77) reported length of hospital stay (days) and
noted a significant reduction in length of stay between CL and ND groups
favouring the CL group (weighted mean difference (WMD) -13 days, 95% CI -23 to
2, I(2) = 0%; no heterogeneity). The quality of the evidence according to GRADE
was low for this outcome. One study (n = 37) reported less crying at 11 weeks'
corrected age (CA) in the CL group compared with the ND group (MD -0.57 hours/24
h, 95% CI -1.09 to -0.05). Tests for heterogeneity were not applicable.Three
studies enrolling 120 infants compared CL versus CBL. Two studies (n = 79)
reported significantly shorter length of stay in the CL group compared with the
CBL group (WMD -16.5 days, 95% CI -26.2 to -6.8, I(2) = 0%; no heterogeneity).
The quality of the evidence according to GRADE was low for this outcome. One
study (n = 41) reported higher mean weight at three months' CA among infants
cared for in the CL nursery (P value < 0.02) and a lower mean number of hours
spent awake in 24 hours at three months of age (P value < 0.005). Data could not
be entered into RevMan or GRADE. One study (n = 41) reported shorter time on the
ventilator in the CL compared with the CBL group (MD -18.2 days, 95% CI -31.40 to
-5.0). One study (n = 41) reported a shorter time to first oral feeding in the CL
group (MD -6.8 days, 95% CI -13.29 to -0.31). We identified no safety issues.
AUTHORS' CONCLUSIONS: Trials assessing the effects of CL have enrolled 544
infants. No study reported on our primary outcome of weight at three or six
months. Results from one additional study strengthen our findings that CL versus
CBL shortens length of stay, as does CL versus ND. The quality of the evidence on
both comparisons for this outcome according to GRADE was low. Future research
should focus on comparing CL versus ND.
PMID- 27508360
TI - CFD for wastewater treatment: an overview.
AB - Computational fluid dynamics (CFD) is a rapidly emerging field in wastewater
treatment (WWT), with application to almost all unit processes. This paper
provides an overview of CFD applied to a wide range of unit processes in water
and WWT from hydraulic elements like flow splitting to physical, chemical and
biological processes like suspended growth nutrient removal and anaerobic
digestion. The paper's focus is on articulating the state of practice and
research and development needs. The level of CFD's capability varies between
different process units, with a high frequency of application in the areas of
final sedimentation, activated sludge basin modelling and disinfection, and
greater needs in primary sedimentation and anaerobic digestion. While approaches
are comprehensive, generally capable of incorporating non-Newtonian fluids,
multiphase systems and biokinetics, they are not broad, and further work should
be done to address the diversity of process designs. Many units have not been
addressed to date. Further needs are identified throughout, but common
requirements include improved particle aggregation and breakup (flocculation),
and improved coupling of biology and hydraulics.
PMID- 27508361
TI - Electrocoagulation and nanofiltration integrated process application in
purification of bilge water using response surface methodology.
AB - Marine pollution has been considered an increasing problem because of the
increase in sea transportation day by day. Therefore, a large volume of bilge
water which contains petroleum, oil and hydrocarbons in high concentrations is
generated from all types of ships. In this study, treatment of bilge water by
electrocoagulation/electroflotation and nanofiltration integrated process is
investigated as a function of voltage, time, and initial pH with aluminum
electrode as both anode and cathode. Moreover, a commercial NF270 flat-sheet
membrane was also used for further purification. Box-Behnken design combined with
response surface methodology was used to study the response pattern and determine
the optimum conditions for maximum chemical oxygen demand (COD) removal and
minimum metal ion contents of bilge water. Three independent variables, namely
voltage (5-15 V), initial pH (4.5-8.0) and time (30-90 min) were transformed to
coded values. The COD removal percent, UV absorbance at 254 nm, pH value (after
treatment), and concentration of metal ions (Ti, As, Cu, Cr, Zn, Sr, Mo) were
obtained as responses. Analysis of variance results showed that all the models
were significant except for Zn (P > 0.05), because the calculated F values for
these models were less than the critical F value for the considered probability
(P = 0.05). The obtained R(2) and Radj(2) values signified the correlation
between the experimental data and predicted responses: except for the model of Zn
concentration after treatment, the high R(2) values showed the goodness of fit of
the model. While the increase in the applied voltage showed negative effects, the
increases in time and pH showed a positive effect on COD removal efficiency; also
the most effective linear term was found as time. A positive sign of the
interactive coefficients of the voltage-time and pH-time systems indicated
synergistic effect on COD removal efficiency, whereas interaction between voltage
and pH showed an antagonistic effect.
PMID- 27508362
TI - Biosurfactant production and its effects on solubilization activity of
phenanthrene: a longitudinal study.
AB - Pseudomonas facilis and Pseudomonasspp., isolated on the basis of its ability to
grow on polycyclic aromatic hydrocarbon, was assayed for biosurfactant production
(BP) potentials by measuring the surface tension (ST) of the culture supernatant
at different time intervals. The strains in three levels of initial inoculum size
(OD600 nm = 0.5, 1, 1.5) were added to medium to determine if bacterial inoculum
size affects solubilization of phenanthrene (PHE).The result showed that although
the two strains reduced the mean ST to less than 34.12 mN m(-1) at the end of day
6, mean solubilization activity of PHE reached 77.05 mg L(-1) on the sixth day.
There was a significant increase in BP over time (P = 0.008); reaching its peak,
157.84 mg L(-1), at the end of the sixth day. Mean solubilization activity of PHE
was not significantly different for the two strains (P = 0.216). The time-course
study revealed that the ST reduction and BP potential was enhanced as inoculation
size increased, leading to higher PHE solubility during the incubation time.
However, the trend of increase in PHE solubility was not totally in the same way
to cell growth and BP. It may be suggested that more bacterial density needs to
be inoculated for practical application of effective bioremediation.
PMID- 27508363
TI - Treatment of leather industrial wastewater via combined advanced oxidation and
membrane filtration.
AB - The liming/unhairing operation is among the important processes of the leather
industry. It generates large amounts of effluent that are highly loaded with
organic hazard wastes. Such effluent is considered one of the most obnoxious
materials in the leather industry, causing serious environmental pollution and
health risks. The effluent is characterized by high concentrations of the
pollution parameters. Conventional chemical and/or biological treatment of such
wastewater is inefficient to meet the required limits of standard specifications,
due to the presence of resistant and toxic compounds. The present investigation
deals with an effective treatment approach for the lime/unhair effluent using the
Fenton reaction followed by membrane filtration. The experiment was extended to a
laboratory pilot-scale in a continuous treatment study. In this study the raw
wastewater was treated with the predetermined Fenton's optimum dose followed by
membrane filtration. The wastewater was efficiently treated and the final
effluent met the standards for unrestricted water reuse.
PMID- 27508364
TI - Influence of different anoxic time exposures on active biomass, protozoa and
filamentous bacteria in activated sludge.
AB - Medium-sized wastewater treatment plants are considered too small to implement
anaerobic digestion technologies and too large for extensive treatments. A
promising option as a sewage sludge reduction method is the inclusion of anoxic
time exposures. In the present study, three different anoxic time exposures of
12, 6 and 4 hours have been studied to reduce sewage sludge production. The best
anoxic time exposure was observed under anoxic/oxic cycles of 6 hours, which
reduced 29.63% of the biomass production compared with the oxic control
conditions. The sludge under different anoxic time exposures, even with a lower
active biomass concentration than the oxic control conditions, showed a much
higher metabolic activity than the oxic control conditions. Microbiological
results suggested that both protozoa density and abundance of filamentous
bacteria decrease under anoxic time exposures compared to oxic control
conditions. The anoxic time exposures 6/6 showed the highest reduction in both
protozoa density, 37.5%, and abundance of filamentous bacteria, 41.1%, in
comparison to the oxic control conditions. The groups of crawling ciliates,
carnivorous ciliates and filamentous bacteria were highly influenced by the
anoxic time exposures. Protozoa density and abundance of filamentous bacteria
have been shown as promising bioindicators of biomass production reduction.
PMID- 27508365
TI - Stimulation of the hydrolytic stage for biogas production from cattle manure in
an electrochemical bioreactor.
AB - Electrical current in the hydrolytic phase of the biogas process might affect
biogas yield. In this study, four 1,150 mL single membrane-less chamber
electrochemical bioreactors, containing two parallel titanium plates were
connected to the electrical source with voltages of 0, -0.5, -1 and -1.5 V,
respectively. Reactor 1 with 0 V was considered as a control reactor. The trend
of biogas production was precisely checked against pH, oxidation reduction
potential and electrical power at a temperature of 37 +/- 0.5 degrees C amid
cattle manure as substrate for 120 days. Biogas production increased by voltage
applied to Reactors 2 and 3 when compared with the control reactor. In addition,
the electricity in Reactors 2 and 3 caused more biogas production than Reactor 4.
Acetogenic phase occurred more quickly in Reactor 3 than in the other reactors.
The obtained results from Reactor 4 were indicative of acidogenic domination and
its continuous behavior under electrical stimulation. The results of the present
investigation clearly revealed that phasic electrical current could enhance the
efficiency of biogas production.
PMID- 27508366
TI - A novel PSB-EDI system for high ammonia wastewater treatment, biomass production
and nitrogen resource recovery: PSB system.
AB - A novel process coupling photosynthetic bacteria (PSB) with electrodeionization
(EDI) treatment was proposed to treat high ammonia wastewater and recover bio
resources and nitrogen. The first stage (PSB treatment) was used to degrade
organic pollutants and accumulate biomass, while the second stage (EDI) was for
nitrogen removal and recovery. The first stage was the focus in this study. The
results showed that using PSB to transform organic pollutants in wastewater into
biomass was practical. PSB could acclimatize to wastewater with a chemical oxygen
demand (COD) of 2,300 mg/L and an ammonia nitrogen (NH4(+)-N) concentration of
288-4,600 mg/L. The suitable pH was 6.0-9.0, the average COD removal reached 80%,
and the biomass increased by an average of 9.16 times. The wastewater COD removal
was independent of the NH4(+)-N concentration. Moreover, the PSB functioned
effectively when the inoculum size was only 10 mg/L. The PSB-treated wastewater
was then further handled in an EDI system. More than 90% of the NH4(+)-N was
removed from the wastewater and condensed in the concentrate, which could be used
to produce nitrogen fertilizer. In the whole system, the average NH4(+)-N removal
was 94%, and the average NH4(+)-N condensing ratio was 10.0.
PMID- 27508367
TI - Application of lactic acid bacteria in removing heavy metals and aflatoxin B1
from contaminated water.
AB - In this study selected lactic acid bacteria (LAB, Lactobacillus acidophilus,
Lactobacillus rhamnosus, Lactobacillus plantrium and Streptococcus thermophiles)
and probiotic bacteria (Bifidobacterium angulatum) were tested for their ability
in removing heavy metals (HM) including cadmium (Cd), lead (Pb) and arsenic (As)
as well as aflatoxin B1 (AFB1) from contaminated water. The biosorption
parameters (pH, bacterial concentration, contact time and temperature) of removal
using individual as well as mixed LAB and probiotic bacteria were studied.
Removal of HM and AFB1 depended on the strain, wherein the process was strongly
pH-dependent with high removal ability at a pH close to neutral. The increase in
bacterial concentration enhanced the removal of Cd, Pb and As. Also, increasing
of contact time and temperature increased the ability of LAB to remove HM. The
effect of contact time on Cd removal was slightly different when freshly cultured
cells were used. The removal of Cd, Pb and As decreased with the increase in the
initial metal concentration. The most effective HM removers were Lactobacillus
acidophilus and Bifidobacterium angulatum. The system was found to be adequate
for concentrations of HM under investigation. At the end of the operation, the
concentration of HM reached the level allowed by the World Health Organization
regulations.
PMID- 27508368
TI - Pd/RGO modified carbon felt cathode for electro-Fenton removing of EDTA-Ni.
AB - Ethylenediaminetetraacetic acid (EDTA) forms stable complexes with toxic metals
such as nickel due to its strong chelation. The electro-Fenton (EF) process using
a cathode made from palladium (Pd), reduced graphene oxide (RGO) and carbon felt,
fed with air, exhibited high activities and stability for the removal of 10 mg L(
1) EDTA-Ni solution. Pd/RGO catalyst was prepared by one-pot synthesis; the
scanning electron microscopy and X-ray diffraction analysis indicated
nanoparticles and RGO were well distributed on carbon felt, forming three
dimensional architecture with both large macropores and a mesoporous structure.
The cyclic voltammetric results showed that the presence of RGO in Pd/RGO/carbon
felt significantly increased the current response of two-electron reduction of O2
(0.45 V). The key factors influencing the removal efficiency of EDTA-Ni, such as
pH, current and Fe(2+) concentration, were investigated. Under the optimum
conditions, the removal efficiency of EDTA-Ni reached 83.8% after 100 min EF
treatment. Mechanism analysis indicated that the introduction of RGO in
Pd/RGO/carbon felt significantly enhanced the electrocatalytic activities by
inducing *OH in the EF process; direct H2O2 oxidation still accounted for a large
amount of EDTA-Ni removal efficiency.
PMID- 27508369
TI - Characteristics and kinetics simulation of controlled-release KMnO4 for phenol
remediation.
AB - Controlled-release KMnO4 (CRP) technology has been recently developed as an
improved, highly efficient technique in wastewater treatment. In this study,
batch-style experiments were conducted to evaluate this technology. The release
characteristics of CRP in distilled water and the reaction between CRP and phenol
were studied and fitted using MATLAB software. Results indicated that in
distilled water, temperature (T) and pH value had a larger effect than dissolved
oxygen (DO) concentration on the release characteristics of KMnO4, and this
relationship can be accurately described by the following kinetic equation: logQ
= log[1.141T(0.152)(pH)(-1.0536)(DO)(0.4674)] + [0.0048T(0.3756)(pH)(1.8854)(DO)(
0.0509)]logt. KMnO4 released from CRP can effectively degrade phenol-contaminated
water with different concentrations. A simulated equation (r = -dCA/dt = -15.1705
CA(0.6840)CP(-0.1406)) characterizing phenol degradation was developed using
MATLAB software. Comparison between the theoretical phenol removal rates deduced
by the above two equations and the initial phenol concentration as well as the
CRP dosage with the experimental data indicates that the differences between them
were less than 20%. The results indicate phenol can be effectively removed by CRP
and smaller dosage of KMnO4 was required compared with literature values. The
models can provide guidance for CRP application in real polluted sites, which can
lower the cost for site remediation.
PMID- 27508370
TI - Effects of the combination of aeration and biofilm technology on transformation
of nitrogen in black-odor river.
AB - Excess nitrogen in urban river networks leading to eutrophication has become one
of the most urgent environmental problems. Combinations of different aeration and
biofilm techniques was designed to remove nitrogen from rivers. In laboratory
water tank simulation experiments, we assessed the removal efficiency of nitrogen
in both the overlying water and sediments by using the combination of the
aeration and biofilm techniques, and then analyzed the transformation of nitrogen
during the experiments. Aeration (especially sediment aeration) combined with the
biofilms techniques was proved efficient in removing nitrogen from polluted
rivers. Results indicated that the combination of sediment aeration and biofilms,
with the highest nitrogen removal rate from the overlying water and sediments,
was the most effective combined process, which especially inhibited the potential
release of nitrogen from sediments by reducing the enzyme activity. It was found
that the content of dissolved oxygen in water could be restored on the basis of
the application of aeration techniques ahead, and the biofilm technique would be
effective in purifying water in black-odor rivers.
PMID- 27508371
TI - Adsorption of the harmful hormone ethinyl estradiol inside hydrophobic cavities
of CTA(+) intercalated montmorillonite.
AB - Hydrophobic cavities produced by cetyltrimethylammonium cation (CTA(+)) exchanged
and trapped in the interlayer space of montmorillonite were used to remove the
harmful hormone contaminant ethinyl estradiol (EE2) from water. X-ray
diffraction, thermogravimetry/derivative thermogravimetry, elemental analysis
(carbon, hydrogen, nitrogen), Fourier transform infrared, scanning electron
microscopy/energy dispersive spectroscopy, Brunauer-Emmett-Teller and contact
angle analyses showed that the intercalation of 9, 16 and 34 wt% CTA(+) in the
montmorillonite resulted in the d001 expansion from 1.37 to 1.58, 2.09 and 2.18
nm, respectively. EE2 adsorption experiments showed that the original clay
montmorillonite does not remove EE2 from water whereas the intercalated
composites showed high efficiency with adsorption capacities of 4.3, 8.8 and 7.3
mg g(-1) for M9CTA(+), M16CTA(+) and M34CTA(+), respectively. Moreover,
experiments with montmorillonite simply impregnated with cetyltrimethylammonium
bromide showed that the intercalation of CTA(+) to form the hydrophobic cavity is
very important for the adsorption properties. Simple solvent extraction can be
used to remove the adsorbed EE2 without significant loss of CTA(+), which allows
the recovery and reuse of the adsorbent for at least five times.
PMID- 27508372
TI - Energy recovery from thermal treatment of dewatered sludge in wastewater
treatment plants.
AB - Sewage sludge is a by-product generated from municipal wastewater treatment (WWT)
processes. This study examines the conversion of sludge via energy recovery from
gasification/combustion for thermal treatment of dewatered sludge. The present
analysis is based on a chemical equilibrium model of thermal conversion of
previously dewatered sludge with moisture content of 60-80%. Prior to
combustion/gasification, sludge is dried to a moisture content of 25-55% by two
processes: (1) heat recovered from syngas/flue gas cooling and (2) heat recovered
from syngas combustion. The electricity recovered from the combined heat and
power process can be reused in syngas cleaning and in the WWT plant. Gas
temperature, total heat and electricity recoverable are evaluated using the
model. Results show that generation of electricity from dewatered sludge with low
moisture content (<= 70%) is feasible within a self-sufficient sludge treatment
process. Optimal conditions for gasification correspond to an equivalence ratio
of 2.3 and dried sludge moisture content of 25%. Net electricity generated from
syngas combustion can account for 0.071 kWh/m(3) of wastewater treated, which is
up to 25.4-28.4% of the WWT plant's total energy consumption.
PMID- 27508373
TI - Optimization design of submerged propeller in oxidation ditch by computational
fluid dynamics and comparison with experiments.
AB - The operating condition of a submerged propeller has a significant impact on flow
field and energy consumption of the oxidation ditch. An experimentally validated
numerical model, based on the computational fluid dynamics (CFD) tool, is
presented to optimize the operating condition by considering two important
factors: flow field and energy consumption. Performance demonstration and
comparison of different operating conditions were carried out in a Carrousel
oxidation ditch at the Yingtang wastewater treatment plants in Anhui Province,
China. By adjusting the position and rotating speed together with the number of
submerged propellers, problems of sludge deposit and the low velocity in the bend
could be solved in a most cost-effective way. The simulated results were
acceptable compared with the experimental data and the following results were
obtained. The CFD model characterized flow pattern and energy consumption in the
full-scale oxidation ditch. The predicted flow field values were within -1.28 +/-
7.14% difference from the measured values. By determining three sets of
propellers under the rotating speed of 6.50 rad/s with one located 5 m from the
first curved wall, after numerical simulation and actual measurement, not only
the least power density but also the requirement of the flow pattern could be
realized.
PMID- 27508374
TI - Estimation of the degree of soil P saturation from Brazilian Mehlich-1 P data and
field investigations on P losses from agricultural sites in Minas Gerais.
AB - The degree of phosphorus saturation (DPS) of agricultural soils is studied
worldwide for risk assessment of phosphorus (P) losses. In previous studies, DPS
could be reliably estimated from water-soluble P (WSP) for European and Brazilian
soils. In the present study, we correlated measured WSP and Mehlich-1 P (M1P)
from soils of Minas Gerais (MG) and Pernambuco (PE) (R(2) = 0.94, n = 59) to
create a DPS map from monitoring data. The resulting DPS map showed high spatial
variability and low values of DPS (54 +/- 22%, mean and standard deviation; n =
1,827). Measured soil DPS values amounted to 63 +/- 14% and resulted in
relatively low dissolved P concentrations measured in a surface runoff study in
MG. However, fertilizer grains on the soil surface led to high WSP values (>30
mg/kg) indicating high risks of dissolved P losses. We suppose that small Oxisol
particles with Fe and Al hydroxides sorbed most of the dissolved fertilizer P in
runoff so that P was mainly exported in particulate form. In soils with lower
contents of P sorption and binding partners, e.g. Entisols in PE, this effect may
be less dominant. Consequently, superficial fertilizer effects have to be
considered in addition to DPS in risk assessment of P losses from agricultural
areas in Brazil.
PMID- 27508375
TI - Facile one pot synthesis of zinc oxide nanorods and statistical evaluation for
photocatalytic degradation of a diazo dye.
AB - In the present work zinc oxide nanorods (ZNRs) have been synthesized to estimate
its photocatalytic degradation potential on an industrially used diazo dye and
optimization of the total treatment process has been designed. Response surface
methodology (RSM) has been used to model the operational parameters for this
photocatalytic degradation. The crystallite size (101 plane) of the synthesized
ZNR has been found to be 20.99 nm having a band gap energy of 3.45 eV. At
elevated pH, the rate of degradation of the photocatalyst was found to be higher
than that of acidic pH. The independent variables of the model are time (9.6-122
min), pH (2-12.2), catalyst dose (0.2-0.4 g/L) and dye concentration (88-512
mg/L). It was seen that the degradation efficiency was significantly affected by
the initial dye concentration and the pH, the optimal values of the parameters
being a pH of 10.67, an initial concentration of 150 mg/L and ZnO dose of 0.37
g/L, the time taken being 88.52 min. The actual degradation efficiency of the dye
reached 96.9% at optimized condition, which is quite close to the predicted value
of 98.07%.
PMID- 27508376
TI - High performance of nitrogen and phosphorus removal in an electrolysis-integrated
biofilter.
AB - A novel electrolysis-integrated biofilter system was developed in this study to
evaluate the intensified removal of nitrogen and phosphorus from contaminated
water. Two laboratory-scale biofilter systems were established, one with
electrolysis (E-BF) and one without electrolysis (BF) as control. The dynamics of
intensified nitrogen and phosphorus removal and the changes of inflow and outflow
water qualities were also evaluated. The total nitrogen (TN) removal rate was
94.4% in our newly developed E-BF, but only 74.7% in the control BF. Ammonium
removal rate was up to 95% in biofilters with or without electrolysis integration
with an influent ammonium concentration of 40 mg/L, and the accumulation of
nitrate and nitrite was much lower in the effluent of E-BF than that of BF. Thus
electrolysis plays an important role in TN removal especially the nitrate and
nitrite removal. Phosphorus removal was significantly enhanced, exceeding 90% in
E-BF by chemical precipitation, physical adsorption, and flocculation of
phosphorus because of the in situ formation of ferric ions by the anodizing of
sacrificial iron anodes. Results from this study indicate that the electrolysis
integrated biofilter is a promising solution for intensified nitrogen and
phosphorus removal.
PMID- 27508377
TI - Longitudinal dispersion in open channel flow with suspended canopies.
AB - Suspended canopies can cause flow disturbances such as reducing velocities within
the canopy, and increasing flow beneath the canopy. Flow modifications by
canopies dramatically affect the fate and transport of sediment, nutrients,
contaminants, dissolved oxygen, and fauna in aquatic systems. A three-zone model
is presented here to predict the longitudinal dispersion coefficient by
simplifying Chikwendu's N-zone model. To validate the model, both flow field and
tracer experiments were conducted using a straight rectangular Plexiglas flume,
with rigid circular rods as the modeled suspended canopies. The result shows that
velocities increased above the flume bed and maximized at a point between the
canopies and flume bed. Above that point, streamwise velocities decreased into
and within the canopies. Reynolds shear stresses were largest at the canopy
interface and smallest (zero) at the velocity maximum point. Good agreement
between the modeled results and experimental data shows that the model can
effectively predict the longitudinal dispersion coefficient in open channels with
suspended canopies.
PMID- 27508378
TI - Effect of pH on the flocculation behaviors of kaolin using a pH-sensitive
copolymer.
AB - pH-sensitive copolymers have been widely introduced to achieve rapid dewatering
and consolidation of solids in mining and oil sands processing wastes. But no
more attention has been given to the flocculation efficiency of solid suspensions
as a function of pH using pH-sensitive copolymer. In this study, a pH-sensitive
copolymer was synthesized and employed to investigate the flocculation behaviors
of kaolin by focused beam reflectance measurement (FBRM). A titration test was
introduced to characterize the copolymer conformation transition. The results
demonstrated that at pH ranging from 3 to 6, with the pH increase, the zeta
potential magnitude of kaolin particles increased, resulting in the repulsive
forces between particles increasing. However, the hydrophobicity of kaolin
increased as the pH increased. Thus, the hydrophobic forces could neutralize a
part of the repulsive forces between particles and result in good and similar
flocculation performances. At the pH greater than 6, the zeta potential magnitude
of kaolin particles and copolymer molecules increased significantly, and the
repulsive force between kaolin particles increased after copolymer addition due
to the kaolin particles being more negatively charged, which resulted in poor
flocculation efficiency and cloudy supernatant. It was concluded that the pH
sensitive copolymer could achieve both perfect flocculation efficiency and low
moisture of filter cake at the isoelectric point of copolymer.
PMID- 27508379
TI - Polyethersulfone/polyacrylonitrile blended ultrafiltration membranes:
preparation, morphology and filtration properties.
AB - Polyethersulfone (PES)/polyacrylonitrile (PAN) membranes have been paid attention
among membrane research subjects. However, very few studies are included in the
literature. In our study, asymmetric ultrafiltration (UF) membranes were prepared
from blends of PES/PAN with phase inversion method using water as coagulation
bath. Polyvinylpyrrolidone (PVP) with Mw of 10,000 Da was used as pore former
agent. N,N-dimethylformamide was used as solvent. The effects of different
percentage of PVP and PES/PAN composition on morphology and water filtration
properties were investigated. Membrane performances were examined using pure
water and lake water filtration studies. Performances of pure water were less
with the addition of PAN into the PES polymer casting solutions. However, long
term water filtration tests showed that PES/PAN blend membranes anti-fouling
properties were much higher than the neat PES membranes. The contact angles of
PES/PAN membranes were lower than neat PES membranes because of PAN addition in
PES polymer casting solutions. Furthermore, it was found that PES/PAN blend UF
membranes' dynamic mechanical analysis properties in terms of Young's modules
were less than neat PES membrane because of decreasing amount of PES polymer.
PMID- 27508380
TI - Microbial risk in wastewater irrigated lettuce: comparing Escherichia coli
contamination from an experimental site with a laboratory approach.
AB - This study assessed the contamination of Escherichia coli, in lettuce grown with
treated domestic wastewater in four different irrigation configurations: open
spray, spray under plastic sheet cover, open drip and drip under plastic sheet
cover. Samples of lettuce from each irrigation configuration and irrigating
wastewater were collected during the growing season. No E. coli was detected in
lettuce from drip irrigated beds. All lettuce samples from spray beds were
positive for E. coli, however, no statistical difference (p > 0.05) was detected
between lettuces grown in open spray or covered spray beds. The results from the
field experiment were also compared to a laboratory experiment which used
submersion of lettuce in wastewater of known E. coli concentration as a surrogate
method to assess contamination following irrigation. The microbial quality of
spray bed lettuces was not significantly different from submersed lettuce when
irrigated with wastewater containing 1,299.7 E. coli MPN/100 mL (p > 0.05). This
study is significant since it is the first to validate that the microbial
contamination of lettuce irrigated with wastewater in the field is comparable
with a laboratory technique frequently applied in the quantitative microbial risk
assessment of the consumption of wastewater irrigated salad crops.
PMID- 27508381
TI - Impact of ozonation in removing organic micro-pollutants in primary and secondary
municipal wastewater: effect of process parameters.
AB - The study investigates the influence of process parameters on the effectiveness
of ozonation in the removal of organic micro-pollutants from wastewater. Primary
and secondary municipal wastewater containing phenol was treated. The effect of
operating parameters such as initial pH, ozone dosage, and initial contaminant
concentration was studied. An increase in contaminant decomposition with pH (3
11) was observed. The contaminant removal efficiencies increased with an increase
in ozone dose rate (5.5-36.17 mg L(-1) min(-1)). Furthermore, the ultraviolet
absorbance (UV 254 nm) of the wastewater decreased during ozonation indicating
the breakdown of complex organic compounds into low molecular weight organics.
Along the reaction, the pH of wastewater decreased from 11 to around 8.5 due to
the formation of intermediate acidic species. Moreover, the biodegradability of
wastewaters, measured as biological and chemical oxygen demand (BOD5/COD),
increased from 0.22 to 0.53. High ozone utilization efficiencies of up to 95%
were attained thereby increasing the process efficiency; and they were dependent
on the ozone dosage and pH of solution. Ozonation of secondary wastewater
attained the South African water standards in terms of COD required for
wastewater discharge and dissolved organic carbon in drinking water and increased
significantly the biodegradability of primary wastewater.
PMID- 27508382
TI - Influences of electroosmosis and electrophoresis on permeate flux and membrane
fouling in submerged membrane bioreactors (SMBRs).
AB - The objective of this study was to investigate the influences of electroosmosis
(EO) and electrophoresis (EP) on the permeate flux in submerged membrane
bioreactors. When a polymeric membrane is placed in between an anode and a
cathode, both EO and EP occur simultaneously, causing enhancement in flux.
Results showed that after 150 min of filtration, the permeate fluxes were 60,
115, 175 and 260 L/m(2)/h at 0, 30, 40 and 50 V, respectively. It was shown that
the EO was linearly changing with increasing voltage, reaching up to 54 L/m(2)/h
at 50 V. EP was found to be a significant process in removing soluble microbial
products from the membrane surface, resulting in an increase in permeate flux as
the filtration progressed. About 20-fold of smaller protein and carbohydrate
concentrations were found in the cake layer when the electrical field (EF) was
applied. However, the EF application promoted pore fouling, because of the
calcium and magnesium scaling.
PMID- 27508383
TI - Erratum: Water Science and Technology 72 (7): Development of a new wastewater
treatment process for resource recovery of carotenoids, H. Sato, H. Nagare, T. N.
C. Huynh and H. Komatsu, doi: 10.2166/wst.2015.330.
AB - A new wastewater treatment process that involves coagulation, ozonation, and
microalgae cultivation has been developed. Here, two challenges are discussed.
The first was minimizing phosphorus removal during coagulation in order to
maximize algal production. The second was to optimize microalgae cultivation;
algal species that grow rapidly and produce valuable products are ideal for
selection. Haematococcus pluvialis, which produces the carotenoid astaxanthin,
was used. Growth rate, nutrient removal ability, and astaxanthin production of H.
pluvialis in coagulated wastewater were investigated. After coagulation with
chitosan, the turbidity and suspended solids decreased by 89% +/- 8% and 73% +/-
16%, respectively. The nitrogen and phosphorus contents of the supernatant
remained at 86% +/- 6% and 67% +/- 24%, respectively. These results indicate that
coagulation with chitosan can remove turbidity and SS while preserving nutrients.
H. pluvialis grew well in the supernatant of coagulated wastewater. The
astaxanthin yield from coagulated wastewater in which microalgae were cultured
was 3.26 mg/L, and total phosphorus and nitrogen contents decreased 99% +/- 1%
and 90% +/- 8% (Days 31-35), respectively.
PMID- 27508384
TI - Integration of Serum Protein Biomarker and Tumor Associated Autoantibody
Expression Data Increases the Ability of a Blood-Based Proteomic Assay to
Identify Breast Cancer.
AB - Despite significant advances in breast imaging, the ability to accurately detect
Breast Cancer (BC) remains a challenge. With the discovery of key biomarkers and
protein signatures for BC, proteomic technologies are currently poised to serve
as an ideal diagnostic adjunct to imaging. Research studies have shown that
breast tumors are associated with systemic changes in levels of both serum
protein biomarkers (SPB) and tumor associated autoantibodies (TAAb). However, the
independent contribution of SPB and TAAb expression data for identifying BC
relative to a combinatorial SPB and TAAb approach has not been fully
investigated. This study evaluates these contributions using a retrospective
cohort of pre-biopsy serum samples with known clinical outcomes collected from a
single site, thus minimizing potential site-to-site variation and enabling direct
assessment of SPB and TAAb contributions to identify BC. All serum samples (n =
210) were collected prior to biopsy. These specimens were obtained from 18
participants with no evidence of breast disease (ND), 92 participants diagnosed
with Benign Breast Disease (BBD) and 100 participants diagnosed with BC,
including DCIS. All BBD and BC diagnoses were based on pathology results from
biopsy. Statistical models were developed to differentiate BC from non-BC (i.e.,
BBD and ND) using expression data from SPB alone, TAAb alone, and a combination
of SPB and TAAb. When SPB data was independently used for modeling, clinical
sensitivity and specificity for detection of BC were 74.7% and 77.0%,
respectively. When TAAb data was independently used, clinical sensitivity and
specificity for detection of BC were 72.2% and 70.8%, respectively. When modeling
integrated data from both SPB and TAAb, the clinical sensitivity and specificity
for detection of BC improved to 81.0% and 78.8%, respectively. These data
demonstrate the benefit of the integration of SPB and TAAb data and strongly
support the further development of combinatorial proteomic approaches for
detecting BC.
PMID- 27508385
TI - Prevalence, Risk Behaviors, and Virological Characteristics of Hepatitis B Virus
Infection in a Group of Men Who Have Sex with Men in Brazil: Results from a
Respondent-Driven Sampling Survey.
AB - BACKGROUND: Men who have sex with men (MSM) are at increased risk of exposure to
hepatitis B virus (HBV) compared with the general population. This study aims to
assess the epidemiological and virological characteristics of HBV infection in a
sample of MSM in Brazil, where data are scarce. METHODS: A cross-sectional study
was conducted among MSM in the City of Goiania, Central Brazil, from March to
November 2014, using Respondent-Driven Sampling (RDS). After signing the consent
form, participants were interviewed and a blood sample collected. All samples
were tested for HBV serological markers and HBV DNA. HBV nucleotide sequence
analysis was also performed. RESULTS: A total of 522 MSM were recruited in the
study. The prevalence of HBV infection (current or past [presence of anti-HBc
marker]) was 15.4% (95% CI: 8.7-25.8) and the rate of HBsAg carriers was 0.6%
(95% CI: 0.2-1.6). About 40% (95% CI: 32.3-48.8) of the participants had
serological evidence of previous HBV vaccination (reactive for isolated anti
HBs). In addition, 44.3% (95% CI: 36.1-52.9) were seronegative for all HBV
markers. Age over 25 years old, receptive anal intercourse, previous sex with
women, and history of sexually transmitted infections (STIs) were factors
associated with HBV infection. HBV DNA was detected only in HBsAg-positive
individuals. HBV isolates were classified into genotype A (subgenotypes A1 and
A2), and some mutations were identified throughout the genome. Therefore, occult
HBV infection was not observed in the study population. CONCLUSIONS: Public
health strategies should be improved for the MSM population in order to prevent
HBV and other STIs, as well as to provide appropriate management of patients with
active infections.
PMID- 27508386
TI - Explaining Lifelong Loyalty: The Role of Identity Fusion and Self-Shaping Group
Events.
AB - Pledging lifelong loyalty to an ingroup can have far-reaching behavioural
effects, ranging from ordinary acts of ingroup kindness to extraordinary acts of
self-sacrifice. What motivates this important form of group commitment? Here, we
propose one especially potent answer to this question-the experience of a
visceral sense of oneness with a group (i.e., identity fusion). In a sample of
British football fans, a population in which high levels of lifelong loyalty are
thought to be common, we first examined the hypothesised relationship between
fusion and perceptions of lifelong loyalty to one's club. We further explored the
hypothesis that fusion and lifelong loyalty are not merely a reflection of past
time investment in a group, but also reflect a deeper, memory-based process of
feeling personally shaped by key group events, both euphoric and dysphoric. We
found broad support for these hypotheses. Results suggest that feeling personally
self-shaped by club events (e.g., crucial wins and losses), rather than time
invested in the club, leads to greater identity fusion to one's club. In turn,
fusion engenders a sense of lifelong club loyalty. We discuss our findings in
relation to the growing literature on the experiential origins of intense social
cohesion.
PMID- 27508387
TI - Phenotypic Plasticity through Transcriptional Regulation of the Evolutionary
Hotspot Gene tan in Drosophila melanogaster.
AB - Phenotypic plasticity is the ability of a given genotype to produce different
phenotypes in response to distinct environmental conditions. Phenotypic
plasticity can be adaptive. Furthermore, it is thought to facilitate evolution.
Although phenotypic plasticity is a widespread phenomenon, its molecular
mechanisms are only beginning to be unravelled. Environmental conditions can
affect gene expression through modification of chromatin structure, mainly via
histone modifications, nucleosome remodelling or DNA methylation, suggesting that
phenotypic plasticity might partly be due to chromatin plasticity. As a model of
phenotypic plasticity, we study abdominal pigmentation of Drosophila melanogaster
females, which is temperature sensitive. Abdominal pigmentation is indeed darker
in females grown at 18 degrees C than at 29 degrees C. This phenomenon is thought
to be adaptive as the dark pigmentation produced at lower temperature increases
body temperature. We show here that temperature modulates the expression of tan
(t), a pigmentation gene involved in melanin production. t is expressed 7 times
more at 18 degrees C than at 29 degrees C in female abdominal epidermis. Genetic
experiments show that modulation of t expression by temperature is essential for
female abdominal pigmentation plasticity. Temperature modulates the activity of
an enhancer of t without modifying compaction of its chromatin or level of the
active histone mark H3K27ac. By contrast, the active mark H3K4me3 on the t
promoter is strongly modulated by temperature. The H3K4 methyl-transferase
involved in this process is likely Trithorax, as we show that it regulates t
expression and the H3K4me3 level on the t promoter and also participates in
female pigmentation and its plasticity. Interestingly, t was previously shown to
be involved in inter-individual variation of female abdominal pigmentation in
Drosophila melanogaster, and in abdominal pigmentation divergence between
Drosophila species. Sensitivity of t expression to environmental conditions might
therefore give more substrate for selection, explaining why this gene has
frequently been involved in evolution of pigmentation.
PMID- 27508388
TI - Protein Profiles for Muscle Development and Intramuscular Fat Accumulation at
Different Post-Hatching Ages in Chickens.
AB - Muscle development and growth influences the efficiency of poultry meat
production, and is closely related to deposition of intramuscular fat (IMF),
which is crucial in meat quality. To clarify the molecular mechanisms underlying
muscle development and IMF deposition in chickens, protein expression profiles
were examined in the breast muscle of Beijing-You chickens at ages 1, 56, 98 and
140 days, using isobaric tags for relative and absolute quantification (iTRAQ).
Two hundred and four of 494 proteins were expressed differentially. The
expression profile at day 1 differed greatly from those at day 56, 98 and 140.
KEGG pathway analysis of differential protein expression from pair-wise
comparisons (day 1 vs. 56; 56 vs. 98; 98 vs. 140), showed that the fatty acid
degradation pathway was more active during the stage from day 1 to 56 than at
other periods. This was consistent with the change in IMF content, which was
highest at day 1 and declined dramatically thereafter. When muscle growth was
most rapid (days 56-98), pathways involved in muscle development were dominant,
including hypertrophic cardiomyopathy, dilated cardiomyopathy, cardiac muscle
contraction, tight junctions and focal adhesion. In contrast with hatchlings, the
fatty acid degradation pathway was downregulated from day 98 to 140, which was
consistent with the period for IMF deposition following rapid muscle growth.
Changes in some key specific proteins, including fast skeletal muscle troponin T
isoform, aldehyde dehydrogenase 1A1 and apolipoprotein A1, were verified by
Western blotting, and could be potential biomarkers for IMF deposition in
chickens. Protein-protein interaction networks showed that ribosome-related
functional modules were clustered in all three stages. However, the functional
module involved in the metabolic pathway was only clustered in the first stage
(day 1 vs. 56). This study improves our understanding of the molecular mechanisms
underlying muscle development and IMF deposition in chickens.
PMID- 27508389
TI - Indoor Air Pollution and Delayed Measles Vaccination Increase the Risk of Severe
Pneumonia in Children: Results from a Case-Control Study in Mwanza, Tanzania.
AB - BACKGROUND: Mortality due to severe pneumonia during childhood in resource
constrained settings is high, but data to provide basis for interventions to
improve survival are limited. The objective of this study was to determine the
risk factors for severe pneumonia in children aged under five years old in
Mwanza, Tanzania. METHODS: We conducted a case-control study of children aged 2
to 59 months at Sekou-Toure regional hospital in Mwanza City, north-western,
Tanzania from May 2013 to March 2014. Cases were children with severe pneumonia
and controls were children with other illnesses. Data on demography, social
economical status, nutritional status, environmental factors, vaccination status,
vitamin A supplementation and deworming, and nasopharyngeal carriage were
collected and analysed using logistic regression. RESULTS: 117 patients were
included in the study. Of these, 45 were cases and 72 controls. Cases were
younger than controls, but there were no differences in social-economic or
nutritional status between the two groups. In multiple regression, we found that
an increased risk of severe pneumonia was associated with cooking indoors (OR
5.5, 95% CI: 1.4, 22.1), and delayed measles vaccination (OR 3.9, 95% CI: 1.1,
14.8). The lack of vitamin A supplementation in the preceding six month and
Enterobacter spp nasopharyngeal carriage were not associated with higher risk of
severe pneumonia. Age >=24 months (OR 0.2, 95% CI: 0.04, 0.8) and not receiving
antibiotics before referral (OR 0.3, 95% CI 0.1, 0.9) were associated with lower
risk for severe pneumonia. CONCLUSIONS: Indoor air pollution and delayed measles
vaccination increase the risk for severe pneumonia among children aged below five
years. Interventions to reduce indoor air pollution and to promote timely
administration of measles vaccination are urgently needed to reduce the burden of
severe pneumonia in children in Tanzania.
PMID- 27508390
TI - Bacterial Loads Measured by the Xpert MTB/RIF Assay as Markers of Culture
Conversion and Bacteriological Cure in Pulmonary TB.
AB - INTRODUCTION: Biomarkers are needed to monitor tuberculosis (TB) treatment and
predict treatment outcomes. We evaluated the Xpert MTB/RIF (Xpert) assay as a
biomarker for TB treatment during and at the end of the 24 weeks therapy.
METHODS: Sputum from 108 HIV-negative, culture-positive pulmonary TB patients was
analyzed using Xpert at time points before and during anti-TB therapy. Results
were compared against culture. Direct Xpert cycle-threshold (Ct), a change in the
Ct (delta Ct), or a novel "percent closing of baseline Ct deficit" (percent
closing) were evaluated as classifiers of same-day and end-of-treatment culture
and therapeutic outcomes. RESULTS: Xpert was positive in 29/95 (30.5%) of
subjects at week 24; and positive one year after treatment in 8/64 (12.5%)
successfully-treated patients who remained free of tuberculosis. We identified a
relationship between initial bacterial load measured by baseline Xpert Ct and
time to culture conversion (hazard ratio 1.06, p = 0.0023), and to the likelihood
of being among the 8 treatment failures at week 24 (AUC = 72.8%). Xpert Ct was
even more strongly associated with culture conversion on the day the test was
performed with AUCs 96.7%, 99.2%, 86.0% and 90.2%, at Day 7, Week 4, 8 and 24,
respectively. Compared to baseline Ct measures alone, a combined measure of
baseline Ct plus either Delta Ct or percent closing improved the classification
of treatment failure status to a 75% sensitivity and 88.9% specificity.
CONCLUSIONS: Genome loads measured by Xpert provide a potentially-useful
biomarker for classifying same day culture status and predicting response to
therapy.
PMID- 27508391
TI - Stimulus Statistics Change Sounds from Near-Indiscriminable to
Hyperdiscriminable.
AB - Objects and events in the sensory environment are generally predictable, making
most of the energy impinging upon sensory transducers redundant. Given this fact,
efficient sensory systems should detect, extract, and exploit predictability in
order to optimize sensitivity to less predictable inputs that are, by definition,
more informative. Not only are perceptual systems sensitive to changes in
physical stimulus properties, but growing evidence reveals sensitivity both to
relative predictability of stimuli and to co-occurrence of stimulus attributes
within stimuli. Recent results revealed that auditory perception rapidly
reorganizes to efficiently capture covariance among stimulus attributes. Acoustic
properties per se were perceptually abandoned, and sounds were instead processed
relative to patterns of co-occurrence. Here, we show that listeners' ability to
distinguish sounds from one another is driven primarily by the extent to which
they are consistent or inconsistent with patterns of covariation among stimulus
attributes and, to a lesser extent, whether they are heard frequently or
infrequently. When sounds were heard frequently and deviated minimally from the
prevailing pattern of covariance among attributes, they were poorly discriminated
from one another. In stark contrast, when sounds were heard rarely and markedly
violated the pattern of covariance, they became hyperdiscriminable with
discrimination performance beyond apparent limits of the auditory system.
Plausible cortical candidates underlying these dramatic changes in perceptual
organization are discussed. These findings support efficient coding of stimulus
statistical structure as a model for both perceptual and neural organization.
PMID- 27508392
TI - The Impact of Macronutrients on Retinal Microvasculature among Singapore Pregnant
Women during the Mid-Late Gestation.
AB - BACKGROUND: Imbalanced macronutrient intakes can induce impairment of endothelial
and vascular function, and further lead to metabolic and cardiovascular disease.
However, little is known about the influence of such diets on endothelial and
vascular dysfunction in pregnant women, even though high-fat diet is a known risk
for pregnancy complications such as gestational diabetes and pre-eclampsia.
OBJECTIVE: We aimed to assess the association between maternal macronutrient
intakes (protein, fat and carbohydrates), dietary quality and retinal
microvascular changes in a multi-ethnic Asian mother-offspring cohort. METHODS:
Pregnant women (n = 614) with singleton pregnancies were recruited during their
first trimester from June 2009 to Sep 2010. Maternal diet quality and
macronutrient intakes, expressed as a percentage of total energy during
pregnancy, were ascertained using 24 hr recalls and 3 d food diaries at 26-28
weeks gestation. Retinal examination was completed at the same clinic visit.
Dietary quality was assessed and scored using the Health Eating Index in Asian
Pregnant women (HEI-AP), while macronutrients intakes ware expressed as
percentages of total energy and further log transformed for analysis.
Associations were examined cross-sectionally by substitution models with the use
of multiple linear regression. RESULTS: In adjusted model, each 20 points
decrease in HEI-AP score was associated with a significant increase of 1.70 MUm
(p<0.05) in retinal venular calibre. Each 0.1 log increase in percentage of total
fat intake was associated with a significant increment of 1.84 MUm (p<0.05) in
retinal venular caliber. Additionally, each 0.1 log increase in percentage of
mono-unsaturated fat intake was associated with an increment of 1.84 MUm (p<0.01)
in retinal venular caliber. CONCLUSIONS: In this cross-sectional study, we found
that women with higher fat and lower protein intakes, and lower diet quality
tended to have wider retinal venular caliber, which is suggestive of suboptimal
microvasculature.
PMID- 27508393
TI - Phenome-Wide Association Study to Explore Relationships between Immune System
Related Genetic Loci and Complex Traits and Diseases.
AB - We performed a Phenome-Wide Association Study (PheWAS) to identify
interrelationships between the immune system genetic architecture and a wide
array of phenotypes from two de-identified electronic health record (EHR)
biorepositories. We selected variants within genes encoding critical factors in
the immune system and variants with known associations with autoimmunity. To
define case/control status for EHR diagnoses, we used International
Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes from 3,024
Geisinger Clinic MyCode(r) subjects (470 diagnoses) and 2,899 Vanderbilt
University Medical Center BioVU biorepository subjects (380 diagnoses). A pooled
analysis was also carried out for the replicating results of the two data sets.
We identified new associations with potential biological relevance including SNPs
in tumor necrosis factor (TNF) and ankyrin-related genes associated with acute
and chronic sinusitis and acute respiratory tract infection. The two most
significant associations identified were for the C6orf10 SNP rs6910071 and
"rheumatoid arthritis" (ICD-9 code category 714) (pMETAL = 2.58 x 10-9) and the
ATN1 SNP rs2239167 and "diabetes mellitus, type 2" (ICD-9 code category 250)
(pMETAL = 6.39 x 10-9). This study highlights the utility of using PheWAS in
conjunction with EHRs to discover new genotypic-phenotypic associations for
immune-system related genetic loci.
PMID- 27508394
TI - Prevalence of psoriatic arthritis and its correlates among patients with
psoriasis in Greece: results from a large retrospective study.
AB - OBJECTIVES: To evaluate the prevalence and its clinical characteristics of
psoriatic arthritis (PsA) in a specialized psoriasis clinic of a University
Hospital. METHODS: In this retrospective study, 278 patients with psoriasis were
evaluated between 2011 and 2013. RESULTS: The study included 278 patients with
psoriasis: 144 (52%) were male and 134 (48%) female. Their median age was 51.41
with median psoriasis presenting age of 34.52 years. Referring to the type of
psoriasis, 86% presented with plaque psoriasis, 5% guttate, 2% palms and soles,
2% inverse, 1% pustular and 4% with psoriasis of more than one type. Nail disease
appeared in 121 patients (43.5%) and scalp disease in 175 (63%). Of these
patients, 85 (30%) had PsA, whereas 51% of patients with PsA had psoriatic nail
disease. With reference to the PsA type, 43 (51%) patients presented with
polyarthritis, 10 (12%) with oligoarthritis, 7 (8%) with axial arthritis, whereas
the rest 25 of them (31%) had PsA of more than one type. The subgroup of patients
with PsA had significantly higher rates of comorbidities including arterial
hypertension, diabetes and hypercholesterolaemia compared to non-PsA patients
with 41% vs. 17% (P = 0.001), 20% vs. 8% (P = 0.021) and 41% vs. 19% (P = 0.004),
respectively. CONCLUSION: The prevalence of PsA among patients with psoriasis was
relatively higher in Greece compared to other ethnic-based studies. Comorbidities
related to life expectancy were more frequent. As there is a high percentage of
undiagnosed cases with active arthritis among patients with psoriasis,
dermatologists should be aware of PsA clinical signs in order to recognize it
earlier and provide successful treatment.
PMID- 27508395
TI - Association between perceived social support and anxiety in pregnant adolescents.
AB - Objective:: To evaluate the association between perceived social support and
anxiety disorders in pregnant adolescents. Methods:: We conducted a cross
sectional study with a sample of 871 pregnant women aged 10 to 19 years who
received prenatal care in the national public health care system in the urban
area of Pelotas, state of Rio Grande do Sul, southern Brazil. We assessed
perceived social support and anxiety disorders using the Medical Outcomes Study
Social Support Survey and the Mini International Neuropsychiatric Interview. A
self-report questionnaire was used to obtain sociodemographic information.
Results:: The prevalence of any anxiety disorder was 13.6%. Pregnant adolescents
with an anxiety disorder reported less perceived social support in all domains
(affectionate, emotional, tangible, informational, and positive social
interaction). Older teenagers reported lower perceived support in the emotional,
informational, and positive social interaction domains, whereas those with low
socioeconomic status reported lower perceived social support in the material
domain. Women who did not live with a partner had less perceived social support
in the affectionate and positive social interaction domains. Conclusion::
Perceived social support seems to be a protective factor against anxiety
disorders in pregnant adolescents, with a positive effect on mental health.
PMID- 27508396
TI - Electroencephalographic findings in patients with major depressive disorder
during cognitive or emotional tasks: a systematic review.
AB - Objective:: Major depressive disorder (MDD) is a prevalent psychiatric condition
characterized by multiple symptoms that cause great distress. Uncovering the
brain areas involved in MDD is essential for improving therapeutic strategies and
predicting response to interventions. This systematic review discusses recent
findings regarding cortical alterations in depressed patients during emotional or
cognitive tasks, as measured by electroencephalography (EEG). Methods:: A search
of the MEDLINE/PubMed and Cochrane databases was carried out using the keywords
EEG and depression, confined to article title. Results:: The studies identified
reveal the frontal cortex as an important brain structure involved in the complex
neural processes associated with MDD. Findings point to disorganization of right
hemisphere activity and deficient cognitive processing in MDD. Depressed
individuals tend to ruminate on negative information and respond with a pattern
of relatively higher right frontal activity to emotional stimuli associated with
withdrawal and isolation. Conclusion:: Patients with MDD may have altered dynamic
patterns of activity in several neuroanatomical structures, especially in
prefrontal and limbic areas involved in affective regulation. Identification of
these alterations might help predict the response of patients to different
interventions more effectively and thus maximize the effects both of
pharmacotherapeutic and of psychotherapeutic strategies.
PMID- 27508397
TI - Components of the metabolic syndrome and depressive symptoms in community
dwelling older people: the Bambui Cohort Aging Study.
AB - OBJECTIVE: To investigate the moderating effect of an increasing number of
clustered metabolic syndrome (MetS) components on the association between MetS
and depressive symptoms in a population-based cohort of older adults in Brazil.
METHODS: This analysis used data from the Bambui Cohort Aging Study. Participants
in this cross-sectional study comprised 1,469 community-dwelling older people
aged >= 60 years. Analyses were performed to assess both the association between
depressive symptoms and each individual MetS component and the association
between depressive symptoms and clustering of an increasing number of MetS
components. RESULTS: High triglyceride level was the individual component that
showed the strongest association with depressive symptoms (odds ratio [OR]: 1.47;
95% confidence intervals [95%CI] 1.19-1.81; p < 0.0001). Only the presence of
three MetS components was associated with depressive symptoms (OR = 1.53; 95%CI
1.05-2.23; p = 0.025). No graded association was detected between increasing
number of clustered MetS components and depressive symptoms. CONCLUSIONS:
Increasing the number of MetS components did not impact the association with
depressive symptoms. The association between high triglyceride level and
depressive symptoms highlights the relevance of lipid metabolism abnormalities
for the emergence of depressive symptoms in older adults.
PMID- 27508398
TI - Impairment of fine motor dexterity in mild cognitive impairment and Alzheimer's
disease dementia: association with activities of daily living.
AB - OBJECTIVE: Cognitive impairment is a hallmark of mild cognitive impairment (MCI)
and Alzheimer's disease dementia (AD). Although the cognitive profile of these
patients and its association with activities of daily living (ADLs) is well
documented, few studies have assessed deficits in fine motor dexterity and their
association with ADL performance. The objective of this research paper is to
evaluate fine motor dexterity performance among MCI and AD patients and to
investigate its association with different aspects of ADLs. METHODS: We assessed
normal aging controls, patients with multiple- and single-domain amnestic MCI
(aMCI), and patients with mild AD. Fine motor dexterity was measured with the
Nine-Hole Peg Test and cognitive functioning by the Mattis Dementia Rating Scale.
We analyzed the data using general linear models. RESULTS: Patients with AD or
multiple-domain aMCI had slower motor responses when compared to controls. AD
patients were slower than those with single-domain aMCI. We found associations
between cognition and instrumental ADLs, and between fine motor dexterity and
self-care ADLs. CONCLUSION: We observed progressive slowing of fine motor
dexterity along the normal aging-MCI-AD spectrum, which was associated with
autonomy in self-care ADLs.
PMID- 27508399
TI - Strategies toward High-Temperature Lanthanide-Based Single-Molecule Magnets.
AB - Lanthanide-based single-molecule magnets are leading materials for achieving
magnetization blocking at the level of one molecule. In this paper, we examine
the physical requirements for efficient magnetization blocking in single-ion
complexes and identify the design principles for achieving very high
magnetization blocking barriers in lanthanide-based compounds. The key condition
is the preponderant covalent binding of the Ln ion to one of the ligand atoms,
tremendously enhancing the axial crystal field. We also make an overview of
practical schemes for the implementation of this principle. These are (1) the
effective lowering of the coordination number via displacement of the Ln ion to
one of the atoms in the coordination polyhedron, (2) the design of two
coordinated complexes, and (3) the stabilization of diatomic compounds in cages
and on surfaces. The last proposal is appealing in connection to spintronics
applications, especially via the exploration of robust and highly anisotropic
[LnX] units displaying multilevel blocking barriers of thousands of Kelvin and
prospects for room-temperature magnetization blocking.
PMID- 27508400
TI - Interplay of Specific Trans- and Juxtamembrane Interfaces in Plexin A3
Dimerization and Signal Transduction.
AB - Plexins are transmembrane proteins that serve as guidance receptors during
angiogenesis, lymphangiogenesis, neuronal development, and zebrafish fin
regeneration, with a putative role in cancer metastasis. Receptor dimerization or
clustering, induced by extracellular ligand binding but modulated in part by the
plexin transmembrane (TM) and juxtamembrane (JM) domains, is thought to drive
plexin activity. Previous studies indicate that isolated plexin TM domains
interact through a conserved, small-x3-small packing motif, and the cytosolic JM
region interacts through a hydrophobic heptad repeat; however, the roles and
interplay of these regions in plexin signal transduction remain unclear. Using an
integrated experimental and simulation approach, we find disruption of the small
x3-small motifs in the Danio rerio Plexin A3 TM domain enhances dimerization of
the TM-JM domain by enhancing JM-mediated dimerization. Furthermore, mutations of
the cytosolic JM heptad repeat that disrupt dimerization do so even in the
presence of TM domain mutations. However, mutations to the small-x3-small TM
interfaces also disrupt Plexin A3 signaling in a zebrafish axonal guidance assay,
indicating the importance of this TM interface in signal transduction.
Collectively, our experimental and simulation results demonstrate that multiple
TM and JM interfaces exist in the Plexin A3 homodimer, and these interfaces
independently regulate dimerization that is important in Plexin A3 signal
transduction.
PMID- 27508401
TI - Air-Driven Potassium Iodide-Mediated Oxidative Photocyclization of Stilbene
Derivatives.
AB - A new method has been developed for the potassium iodide-mediated oxidative
photocyclization of stilbene derivatives. Compared with conventional iodine
mediated oxidative photocyclization reactions, this new method requires shorter
reaction times and affords cyclized products in yields of 45-97%. This reaction
proceeds with a catalytic amount of potassium iodide and works in an air-driven
manner without the addition of an external scavenger. The radical-mediated
oxidative photocyclization of stilbene derivatives using TEMPO was also
investigated.
PMID- 27508402
TI - Factors Associated with the Use of Gene Expression Profiles in Estrogen Receptor
Positive Early-Stage Breast Cancer Patients: A Nationwide Study.
AB - BACKGROUND: Breast cancer guidelines suggest the use of gene expression profiles
(GEPs) in estrogen receptor-positive (ER+) breast cancer patients in whom
controversy exists regarding adjuvant chemotherapy benefit based on traditional
prognostic factors alone. We evaluated the current use of GEPs in these patients
in the Netherlands. PATIENTS AND METHODS: Primary breast cancer patients treated
between January 1, 2011 and December 31, 2014 and eligible for GEP use according
to the Dutch national breast cancer guideline were identified in the Netherlands
Cancer Registry: ER+ patients <70 years with grade 1 tumors >2 cm or grade 2
tumors 1-2 cm without overt lymph node metastases (pN0-Nmi). Mixed-effect
logistic regression analysis was performed to associate characteristics of
patients, tumors and hospitals with GEP use. RESULTS: GEPs were increasingly
deployed: 12% of eligible patients received a GEP in 2011 versus 46% in 2014.
Lobular versus ductal morphology (OR 0.58, 95% CI 0.47-0.72), pN1mi status
(versus pN0, OR 0.52, 95% CI 0.40-0.68), and tumor size (>3 cm vs. >2 cm, OR
0.33, 95% CI 0.14-0.88) were inversely associated with GEP use. High
socioeconomic status (SES) (OR 1.32, 95% CI 1.06-1.64) and younger age (OR
0.96/year increasing age, 95% CI 0.95-0.96) were positively associated with GEP
use. GEP use per hospital did vary, but no predefined institutional factors
remained independently associated with GEP use. CONCLUSION: GEP use increased
over time and was influenced by patient- and tumor-associated factors as well as
by SES.
PMID- 27508403
TI - Characteristic Contrast in Deltafmin Maps of Organic Molecules Using Atomic Force
Microscopy.
AB - Scanning tunneling microscopy and atomic force microscopy can provide detailed
information about the geometric and electronic structure of molecules with
submolecular spatial resolution. However, an essential capability to realize the
full potential of these techniques for chemical applications is missing from the
scanning probe toolbox: chemical recognition of organic molecules. Here, we show
that maps of the minima of frequency shift-distance curves extracted from 3D data
cubes contain characteristic contrast. A detailed theoretical analysis based on
density functional theory and molecular mechanics shows that these features are
characteristic for the investigated species. Structurally similar but chemically
distinct molecules yield significantly different features. We find that the van
der Waals and Pauli interaction, together with the specific adsorption geometry
of a given molecule on the surface, accounts for the observed contrast.
PMID- 27508404
TI - Enhanced Bulk and Interfacial Charge Transfer Dynamics for Efficient
Photoelectrochemical Water Splitting: The Case of Hematite Nanorod Arrays.
AB - Charge transport in the bulk and across the semiconductor/electrolyte interface
is one of the major issues that limits photoelectrochemical (PEC) performance in
hematite photoelectrodes. Efficient charge transport in the entire hematite is of
great importance to obtaining high photoelectrochemical properties. Herein, to
reach this goal, we employed both TiO2 underlayer and overlayer deposition on
hematite nanorod films, followed by a fast annealing treatment. The TiO2
underlayer and overlayer not only serve as dopant sources for carrier density
increase but also reduce charge recombination at the fluorine-doped tin oxide
(FTO)/hematite interface and accelerate charge transfer across the
hematite/electrolyte interface. This synergistic doping and interface modifying
effects give rise to an enhanced photoelectrochemical water oxidation performance
of hematite nanorod arrays, generating an impressive photocurrent density of 1.49
mA cm(-2) at 1.23 V vs RHE. This is the first report on using both underlayer and
overlayer modification with the same material to improve charge transport through
the entire electron transport path in hematite, which provides a novel way to
manipulate charge transfer across the semiconductor interface for a high
performance photoelectrode.
PMID- 27508405
TI - Direct Photolysis Rates and Transformation Pathways of the Lampricides TFM and
Niclosamide in Simulated Sunlight.
AB - The lampricides 3-trifluoromethyl-4-nitrophenol (TFM) and 2',5-dichloro-4'
nitrosalicylanilide (niclosamide) are directly added to many tributaries of the
Great Lakes that harbor the invasive parasitic sea lamprey. Despite their long
history of use, the fate of lampricides is not well understood. This study
evaluates the rate and pathway of direct photodegradation of both lampricides
under simulated sunlight. The estimated half-lives of TFM range from 16.6 +/- 0.2
h (pH 9) to 32.9 +/- 1.0 h (pH 6), while the half-lives of niclosamide range from
8.88 +/- 0.52 days (pH 6) to 382 +/- 83 days (pH 9) assuming continuous
irradiation over a water depth of 55 cm. Both compounds degrade to form a series
of aromatic intermediates, simple organic acids, ring cleavage products, and
inorganic ions. Experimental data were used to construct a kinetic model which
demonstrates that the aromatic products of TFM undergo rapid photolysis and
emphasizes that niclosamide degradation is the rate-limiting step to
dehalogenation and mineralization of the lampricide. This study demonstrates that
TFM photodegradation is likely to occur on the time scale of lampricide
applications (2-5 days), while niclosamide, the less selective lampricide, will
undergo minimal direct photodegradation during its passage to the Great Lakes.
PMID- 27508406
TI - Supramolecular Thermo-Electrochemical Cells: Enhanced Thermoelectric Performance
by Host-Guest Complexation and Salt-Induced Crystallization.
AB - Thermo-electrochemical cells have potential to generate thermoelectric voltage 1
order higher than that given by semiconductor materials. To overcome the current
issues in thermoelectric energy conversion, it is of paramount importance to grow
and fulfill the full potential of thermo-electrochemical cells. Here we report a
rational supramolecular methodology that yielded the highest Seebeck coefficient
of ca. 2.0 mV K(-1) around ambient temperatures. This is based on the
encapsulation of triiodide ions in alpha-cyclodextrin, whose equilibrium is
shifted to the complexation at lower temperatures, whereas it is inverted at
elevated temperatures. This temperature-dependent host-guest interaction provides
a concentration gradient of redox ion pairs between two electrodes, leading to
the eminent performance of the thermo-electrochemical cells. The figure of merit
for this system, zT reached a high value of 5 * 10(-3). The introduction of host
guest chemistry to thermoelectric cells thus provides a new perspective in
thermoelectric energy conversion.
PMID- 27508407
TI - Palladium-Catalyzed Intramolecular Dearomatization of Indoles via Decarboxylative
Alkynyl Termination.
AB - A highly diastereoselective dearomatization of indoles via palladium-catalyzed
decarboxylative alkynyl termination was developed. This protocol provides
dissimilar tetracyclic and tetrasubstituted indoline scaffolds bearing congested
stereocenters, which led to operationally simple conditions, short time, and
broad substrate scope. Additionally, this reaction system could be scaled to gram
quantities in a satisfactory yield and diastereoselectivity.
PMID- 27508408
TI - Transient Two-Dimensional Infrared Spectroscopy in a Vibrational Ladder.
AB - We report on transient 2D Fourier transform infrared spectroscopy (2DIR) after
vibrational ladder climbing induced in the CO-moiety longitudinal stretch of
carboxyhemoglobin. The population distribution, spreading up to seven vibrational
levels, results in a nonequilibrium 2DIR spectrum evidencing a large number of
peaks that can be easily attributed to individual transitions thanks to the
anharmonicity of the vibrational potential. We discuss the physical origin of the
observed peaks as well as the qualitative behavior of the subsequent dynamics
governed by population relaxation in the vibrational ladder.
PMID- 27508409
TI - Use of the Coelomic Grafting Technique for Prolonged ex utero Cultivation of Late
Preprimitive Streak-Stage Rabbit Embryos.
AB - Due to its morphological similarity with the early human embryo, the
pregastrulation-stage rabbit may represent an appropriate mammalian model for
studying processes involved in early human development. The usability of
mammalian embryos for experimental studies depends on the availability of whole
embryo culture methods facilitating prolonged ex utero development. While
currently used culture methods yield high success rates for embryos from
primitive streak stages onward, the success rate of extended cultivation of
preprimitive streak-stage mammalian embryos is low for all previously established
methods and for all studied species. This limits the usability of preprimitive
streak-stage rabbit embryos in experimental embryology. We have tested whether
the extraembryonic coelom of 4-day-old chick embryos may be used for prolonged ex
utero culture of preprimitive streak-stage rabbit embryos (stage 2, 6.2 days post
coitum). We found that, within this environment, stage 2 rabbit blastocysts can
be cultured at decreasing success rates (55% after 1 day, 35% after 2 days, 15%
after 3 days) up to a maximum of 72 h. Grafted blastocysts can continue
development from the onset of gastrulation to early organogenesis and thereby
form all structures characterizing age-matched controls (e.g. neural tube,
somites, beating heart). Compared to normal controls, successfully cultured
embryos developed at a slower rate and finally showed some structural and gross
morphological anomalies. The method presented here was originally developed for
whole embryo culture of mouse embryos by Gluecksohn-Schoenheimer in 1941. It is a
simple and inexpensive method that may represent a useful extension to presently
available ex utero culture systems for rabbit embryos.
PMID- 27508410
TI - Effects of Mulching on Soil Properties and Growth of Tea Olive (Osmanthus
fragrans).
AB - Different mulches have variable effects on soil physical properties and plant
growth. This study aimed to compare the effects of mulching with inorganic (round
gravel, RG), organic (wood chips, WC), and living (manila turf grass, MG)
materials on soil properties at 0-5-cm and 5-10-cm depths, as well as on the
growth and physiological features of Osmanthus fragrans L. 'Rixianggui' plants.
Soil samples were collected at three different time points from field plots of O.
fragrans plants treated with the different mulching treatments. Moisture at both
soil depths was significantly higher after mulching with RG and WC than that in
the unmulched control (CK) treatment. Mulching did not affect soil bulk density,
pH, or total nitrogen content, but consistently improved soil organic matter. The
available nitrogen in the soil increased after RG and WC treatments, but
decreased after MG treatment during the experimental period. Mulching improved
plant growth by increasing root activity, soluble sugar, and chlorophyll a
content, as well as by providing suitable moisture conditions and nutrients in
the root zone. Plant height and trunk diameter were remarkably increased after
mulching, especially with RG and WC. However, while MG improved plant growth at
the beginning of the treatment, the 'Rixianggui' plants later showed no
improvement in growth. This was probably because MG competed with the plants for
water and available nitrogen in the soil. Thus, our findings suggest that RG and
WC, but not MG, improved the soil environment and the growth of 'Rixianggui'
plants. Considering the effect of mulching on soil properties and plant growth
and physiology, round gravel and wood chips appear to be a better choice than
manila turf grass in 'Rixianggui' nurseries. Further studies are required to
determine the effects of mulch quality and mulch-layer thickness on shoot and
root growths.
PMID- 27508411
TI - Accelerating Gene Discovery by Phenotyping Whole-Genome Sequenced Multi-mutation
Strains and Using the Sequence Kernel Association Test (SKAT).
AB - Forward genetic screens represent powerful, unbiased approaches to uncover novel
components in any biological process. Such screens suffer from a major
bottleneck, however, namely the cloning of corresponding genes causing the
phenotypic variation. Reverse genetic screens have been employed as a way to
circumvent this issue, but can often be limited in scope. Here we demonstrate an
innovative approach to gene discovery. Using C. elegans as a model system, we
used a whole-genome sequenced multi-mutation library, from the Million Mutation
Project, together with the Sequence Kernel Association Test (SKAT), to rapidly
screen for and identify genes associated with a phenotype of interest, namely
defects in dye-filling of ciliated sensory neurons. Such anomalies in dye-filling
are often associated with the disruption of cilia, organelles which in humans are
implicated in sensory physiology (including vision, smell and hearing),
development and disease. Beyond identifying several well characterised dye
filling genes, our approach uncovered three genes not previously linked to
ciliated sensory neuron development or function. From these putative novel dye
filling genes, we confirmed the involvement of BGNT-1.1 in ciliated sensory
neuron function and morphogenesis. BGNT-1.1 functions at the trans-Golgi network
of sheath cells (glia) to influence dye-filling and cilium length, in a cell non
autonomous manner. Notably, BGNT-1.1 is the orthologue of human B3GNT1/B4GAT1, a
glycosyltransferase associated with Walker-Warburg syndrome (WWS). WWS is a
multigenic disorder characterised by muscular dystrophy as well as brain and eye
anomalies. Together, our work unveils an effective and innovative approach to
gene discovery, and provides the first evidence that B3GNT1-associated Walker
Warburg syndrome may be considered a ciliopathy.
PMID- 27508412
TI - The Great Irish Famine: Identifying Starvation in the Tissues of Victims Using
Stable Isotope Analysis of Bone and Incremental Dentine Collagen.
AB - The major components of human diet both past and present may be estimated by
measuring the carbon and nitrogen isotope ratios (delta13C and delta15N) of the
collagenous proteins in bone and tooth dentine. However, the results from these
two tissues differ substantially: bone collagen records a multi-year average
whilst primary dentine records and retains time-bound isotope ratios deriving
from the period of tooth development. Recent studies harnessing a sub-annual
temporal sampling resolution have shed new light on the individual dietary
histories of our ancestors by identifying unexpected radical short-term dietary
changes, the duration of breastfeeding and migration where dietary change occurs,
and by raising questions regarding factors other than diet that may impact on
delta13C and delta15N values. Here we show that the dentine delta13C and delta15N
profiles of workhouse inmates dating from the Great Irish Famine of the 19th
century not only record the expected dietary change from C3 potatoes to C4 maize,
but when used together they also document prolonged nutritional and other
physiological stress resulting from insufficient sustenance. In the adults, the
influence of the maize-based diet is seen in the delta13C difference between
dentine (formed in childhood) and rib (representing an average from the last few
years of life). The demonstrated effects of stress on the delta13C and delta15N
values will have an impact on the interpretations of diet in past populations
even in slow-turnover tissues such as compact bone. This technique also has
applicability in the investigation of modern children subject to nutritional
distress where hair and nails are unavailable or do not record an adequate period
of time.
PMID- 27508413
TI - Demography of the Early Neolithic Population in Central Balkans: Population
Dynamics Reconstruction Using Summed Radiocarbon Probability Distributions.
AB - The Central Balkans region is of great importance for understanding the spread of
the Neolithic in Europe but the Early Neolithic population dynamics of the region
is unknown. In this study we apply the method of summed calibrated probability
distributions to a set of published radiocarbon dates from the Republic of Serbia
in order to reconstruct population dynamics in the Early Neolithic in this part
of the Central Balkans. The results indicate that there was a significant
population growth after ~6200 calBC, when the Neolithic was introduced into the
region, followed by a bust at the end of the Early Neolithic phase (~5400 calBC).
These results are broadly consistent with the predictions of the Neolithic
Demographic Transition theory and the patterns of population booms and busts
detected in other regions of Europe. These results suggest that the cultural
process that underlies the patterns observed in Central and Western Europe was
also in operation in the Central Balkan Neolithic and that the population
increase component of this process can be considered as an important factor for
the spread of the Neolithic as envisioned in the demic diffusion hypothesis.
PMID- 27508414
TI - Risk of Nephrotic Syndrome following Enteroviral Infection in Children: A
Nationwide Retrospective Cohort Study.
AB - PURPOSE: Nephrotic syndrome is a common chronic illness encountered during
childhood. Infections have been identified as a cause of nephrotic syndrome. The
aim of this study was to evaluate the association between enteroviral infection
and nephrotic syndrome. METHODS: A nationwide retrospective cohort study was
conducted by analyzing data from the National Health Insurance Research Database
in Taiwan. Children aged <18 years with enteroviral infection were enrolled. Non
enterovirus-infected children were randomly selected as the comparison cohort.
The primary endpoint was the occurrence of nephrotic syndrome. METHODS: This
study included 280,087 enterovirus-infected children and 280,085 non-enterovirus
infected children. The mean age of the enterovirus-infected children was 2.38
years, and 53.7% of these children were boys. The overall incidence densities of
nephrotic syndrome for enterovirus- and non-enterovirus-infected children were
2.65 and 2.21 per 10,000 person-years, respectively. The enterovirus-infected
cohort had a higher cumulative incidence of nephrotic syndrome than did the non
enterovirus-infected cohort (log-rank test, p = 0.01). Multivariable analyses
revealed that children with enteroviral infection were significantly associated
with an increased risk of nephrotic syndrome compared with those without
enteroviral infection (adjusted hazard ratio, 1.20; 95% confidence interval, 1.04
1.39; p = 0.01), particularly in children infected with coxsackievirus. Subgroup
analyses revealed that enterovirus-infected girls, children of blue-collar
workers, and children without allergies had a higher risk of nephrotic syndrome
than did children in the non-enterovirus-infected cohort. CONCLUSION: This study
revealed a significant association between enteroviral infection and nephrotic
syndrome. Additional studies elucidating the role and pathogenesis of enterovirus
in nephrotic syndrome are warranted.
PMID- 27508415
TI - Assumptions of Mixed Treatment Comparisons in Health Technology Assessments -
Challenges and Possible Steps for Practical Application.
AB - The validity of mixed treatment comparisons (MTCs), also called network meta
analysis, relies on whether it is reasonable to accept the underlying assumptions
on similarity, homogeneity, and consistency. The aim of this paper is to propose
a practicable approach to addressing the underlying assumptions of MTCs. Using
data from clinical studies of antidepressants included in a health technology
assessment (HTA), we present a stepwise approach to dealing with challenges
related to checking the above assumptions and to judging the robustness of the
results of an MTC. At each step, studies that were dissimilar or contributed to
substantial heterogeneity or inconsistency were excluded from the primary
analysis. In a comparison of the MTC estimates from the consistent network with
the MTC estimates from the homogeneous network including inconsistencies, few
were affected by notable changes; that is, a change in effect size (factor 2),
direction of effect or statistical significance. Considering the small proportion
of studies excluded from the network due to inconsistency, as well as the number
of notable changes, the MTC results were deemed sufficiently robust. In the
absence of standard methods, our approach to checking assumptions in MTCs may
inform other researchers in need of practical options, particularly in HTA.
PMID- 27508416
TI - Integrative Inferences on Pattern Geometries of Grapes Grown under Water Stress
and Their Resulting Wines.
AB - Multiple datasets of two consecutive vintages of replicated grape and wines from
six different deficit irrigation regimes are characterized and compared. The
process consists of four temporal-ordered signature phases: harvest field data,
juice composition, wine composition before bottling and bottled wine. A new
computing paradigm and an integrative inferential platform are developed for
discovering phase-to-phase pattern geometries for such characterization and
comparison purposes. Each phase is manifested by a distinct set of features,
which are measurable upon phase-specific entities subject to the common set of
irrigation regimes. Throughout the four phases, this compilation of data from
irrigation regimes with subsamples is termed a space of media-nodes, on which
measurements of phase-specific features were recoded. All of these collectively
constitute a bipartite network of data, which is then normalized and binary
coded. For these serial bipartite networks, we first quantify patterns that
characterize individual phases by means of a new computing paradigm called "Data
Mechanics". This computational technique extracts a coupling geometry which
captures and reveals interacting dependence among and between media-nodes and
feature-nodes in forms of hierarchical block sub-matrices. As one of the
principal discoveries, the holistic year-factor persistently surfaces as the most
inferential factor in classifying all media-nodes throughout all phases. This
could be deemed either surprising in its over-arching dominance or obvious based
on popular belief. We formulate and test pattern-based hypotheses that confirm
such fundamental patterns. We also attempt to elucidate the driving force
underlying the phase-evolution in winemaking via a newly developed partial
coupling geometry, which is designed to integrate two coupling geometries. Such
partial coupling geometries are confirmed to bear causal and predictive
implications. All pattern inferences are performed with respect to a profile of
energy distributions sampled from network bootstrapping ensembles conforming to
block-structures specified by corresponding hypotheses.
PMID- 27508417
TI - The 4p16.3 Parkinson Disease Risk Locus Is Associated with GAK Expression and
Genes Involved with the Synaptic Vesicle Membrane.
AB - Genome-wide association studies (GWAS) have identified the GAK/DGKQ/IDUA region
on 4p16.3 among the top three risk loci for Parkinson's disease (PD), but the
specific gene and risk mechanism are unclear. Here, we report transcripts
containing the 3' clathrin-binding domain of GAK identified by RNA deep
sequencing in post-mortem human brain tissue as having increased expression in
PD. Furthermore, carriers of 4p16.3 PD GWAS risk SNPs show decreased expression
of one of these transcripts, GAK25 (Gencode Transcript 009), which correlates
with the expression of genes functioning in the synaptic vesicle membrane.
Together, these findings provide strong evidence for GAK clathrin-binding- and J
domain transcripts' influence on PD pathogenicity, and for a role for GAK in
regulating synaptic function in PD.
PMID- 27508418
TI - Twelve-Month and Lifetime Prevalence of Mental Disorders in Cancer Patients.
AB - BACKGROUND: Psychological problems are common in cancer patients. For the purpose
of planning psycho-oncological interventions and services tailored to the
specific needs of different cancer patient populations, it is necessary to know
to what extent psychological problems meet the criteria of mental disorders. The
purpose of this study was to estimate the 12-month and lifetime prevalence rates
of mental disorders in cancer patients. METHODS: A representative sample of
patients with different tumour entities and tumour stages (n = 2,141) in
outpatient, inpatient and rehabilitation settings underwent the standardized
computer-assisted Composite International Diagnostic Interview for mental
disorders adapted for cancer patients (CIDI-O). RESULTS: The overall 12-month
prevalence for any mental disorder was 39.4% (95% CI: 37.3-41.5), that for
anxiety disorders was 15.8% (95% CI: 14.4-17.4), 12.5% (95% CI: 11.3-14.0) for
mood disorders, 9.5% (95% CI: 8.3-10.9) for somatoform disorders, 7.3% (95% CI:
6.2-8.5) for nicotine dependence, 3.7% (95% CI: 3.0-4.6) for disorders due to
general medical condition, and 1.1% (95% CI: 0.7-1.6) for alcohol abuse or
dependence. Lifetime prevalence for any mental disorder was 56.3% (95% CI 54.1
58.6), that for anxiety disorders was 24.1% (95% CI: 22.3-25.9), 20.5% (95% CI:
18.9-22.3) for mood disorders, 19.9% (95% CI: 18.3-21.7) for somatoform
disorders, 18.2% (95% CI: 16.6-20.0) for nicotine dependence, 6.4% (95% CI: 5.4
7.6) for alcohol abuse or dependence, 4.6% (95% CI: 3.8-5.6) for disorders due to
general medical condition, and 0.2% (95% CI: 0.1-0.6) for eating disorders.
CONCLUSIONS: Mental disorders are highly prevalent in cancer patients, indicating
the need for provision of continuous psycho-oncological support from inpatient to
outpatient care, leading to an appropriate allocation of direct personnel and
other resources.
PMID- 27508419
TI - Preservation Obscures Pelagic Deep-Sea Fish Diversity: Doubling the Number of
Sole-Bearing Opisthoproctids and Resurrection of the Genus Monacoa
(Opisthoproctidae, Argentiniformes).
AB - The family Opisthoproctidae (barreleyes) constitutes one of the most peculiar
looking and unknown deep-sea fish groups in terms of taxonomy and specialized
adaptations. All the species in the family are united by the possession of
tubular eyes, with one distinct lineage exhibiting also drastic shortening of the
body. Two new species of the mesopelagic opisthoproctid mirrorbelly genus Monacoa
are described based on pigmentation patterns of the "sole"-a unique vertebrate
structure used in the reflection and control of bioluminescence in most short
bodied forms. Different pigmentation patterns of the soles, previously noted as
intraspecific variations based on preserved specimens, are here shown species
specific and likely used for communication in addition to counter-illumination of
down-welling sunlight. The genus Monacoa is resurrected from Opisthoproctus based
on extensive morphological synaphomorphies pertaining to the anal fin and snout.
Doubling the species diversity within sole-bearing opisthoproctids, including
recognition of two genera, is unambiguously supported by mitogenomic DNA sequence
data. Regular fixation with formalin and alcohol preservation is shown
problematic concerning the retention of species-specific pigmentation patterns.
Examination or photos of fresh material before formalin fixation is shown
paramount for correct species recognition of sole-bearing opisthoproctids-a
relatively unknown issue concerning species diversity in the deep-sea pelagic
realm.
PMID- 27508421
TI - Numerical Simulation and Experimental Validation of Calibrant-Loaded Extraction
Phase Standardization Approach.
AB - We present the kinetics of calibrant release and analyte uptake between the
sample and calibrant-loaded extraction phase, CL-EP, with a finite-element
analysis (FEA) using COMSOL Multiphysics software package. Effect of finite and
infinite sample volume conditions, as well as various sample environment
parameters such as fluid flow velocity, temperature, and presence of a binding
matrix component were investigated in detail with the model in relation to the
performance of the calibration. The simulation results supported by experimental
data demonstrate the suitability of the CL-EP method for analysis of samples with
variation of the sample environment parameters. The calibrant-loaded approach can
provide both total and free concentrations from a single experiment based on
whether the partition coefficient (Kes) value being used is measured in a matrix
matched sample or in a matrix-free sample, respectively. Total concentrations can
also be obtained by utilizing CL-EP in combination with external matrix-matched
calibrations, which can be employed to automate the sampling process and provide
corrections for variations in sample preparation, matrix effects, and detection
processes. This approach is also suitable for very small volumes of sample, where
addition of an internal standard in the sample is either troublesome or can
change the sample characteristics.
PMID- 27508420
TI - Number of Persistent Organic Pollutants Detected at High Concentrations in Blood
Samples of the United States Population.
AB - Human exposure to environmental chemicals as persistent organic pollutants (POPs)
is usually assessed considering each pollutant individually, with little
attention to concentrations of mixtures in individuals or social groups. Yet, it
may be relatively common for humans to have low and high concentrations of
numerous POPs. The study objectives were to analyze the number of POPs detected
per person at high concentrations in the U.S. population, and the associations
between such type of indicators and socioeconomic factors as gender, race /
ethnicity, education, and poverty level. From 91 POPs analyzed in serum samples
of 4,739 individuals in three subsamples of the National Health and Nutrition
Examination Survey (NHANES) 2003-2004 (the last period with valid updated
individual data for the compounds considered in the present study), we computed
the number of POPs whose serum concentrations were above selected cutoff points.
POPs included were 13 organochlorine compounds (OCs), 10 polybrominated diphenyl
ethers (PBDEs), the polybrominated biphenyl (PBB) 153, 38 polychlorinated
biphenyls (PCBs), 17 polychlorinated dibenzo-p-dioxins and dibenzofurans
(PCDDs/Fs), and 12 perfluorinated compounds (PFCs). Over 13% of participants had
>=10 of the 37 most detected POPs each at a concentration in the top decile
(P90). Over 30% of subjects with total toxic equivalency (TEQ) >=P75, had >=10 of
24 POPs not included in TEQ calculations at concentrations >=P90. Compared to non
Hispanic whites, the adjusted odds ratio of having >=10 of the 37 POPs at P90 was
9.2 for non-Hispanic blacks and 0.18 for Mexican Americans. Poverty, body mass
index, age, and gender were also independently associated with having >=10 POPs
in the top decile. More than one tenth of the US population may have >=10 POPs
each at concentrations in the top decile. Such pattern is nine times more
frequent in Non-Hispanic blacks and four times less frequent in Mexican Americans
than in non-Hispanic whites.
PMID- 27508422
TI - LARGE RETINAL PIGMENT EPITHELIAL RIP ASSOCIATED WITH BULLOUS RETINAL AND
CHOROIDAL DETACHMENT.
AB - PURPOSE: To report a giant retinal pigment epithelium rip in a patient with a
bullous retinal and choroidal detachment. METHODS: Case report with widefield
imaging, fundus autofluorescence, and optical coherence tomography of the retina.
RESULTS: This 62-year-old patient had a history of advanced glaucoma,
trabeculectomy, blebitis, and endophthalmitis. He had cataract surgery 6 weeks
before presentation. He was found to have a large bullous retinal and choroidal
detachment with a large retinal pigment epithelium tear at the limit of the
choroidal detachment. After vitrectomy for retinal detachment repair, the tear
was observed to extend inferiorly at the margins of the choroidal detachment.
CONCLUSION: This case report demonstrates that large retinal pigment epithelium
rips can be found associated with large bullous choroidal and retinal
detachments. These tears seem similar to tears that have been observed after
trabeculectomy.
PMID- 27508423
TI - EN FACE OPTICAL COHERENCE TOMOGRAPHY (OCT) AND OCT ANGIOGRAPHY FINDINGS IN
RETINAL ASTROCYTIC HAMARTOMAS.
AB - PURPOSE: To report spectral-domain optical coherence tomography, en face optical
coherence tomography (OCT), and optical coherence tomography angiography findings
in retinal astrocytic hamartomas. METHODS: Four cases of retinal astrocytic
hamartomas, with small white or yellowish typical retinal mass, were imaged with
fundus photography, intravenous fluorescein angiography, fundus autofluorescence,
spectral-domain OCT, en face OCT, and OCT angiography. RESULTS: The tumor was
solitary in all cases and involved the posterior pole. It was idiopathic in three
cases and was related to tuberous sclerosis complex in one case. The OCT findings
included intralesional lucencies in two cases with no exudation. The tumor was
within the retinal nerve fiber layer or deeper, usually overlying the inner
plexiform layer providing a protusion in the vitreous cavity. Vitreous changes
were present in all cases, corresponding to thickening and adhesion of the
vitreous facing the lesion (two cases), apparent interdigitation with vitreous
(one case), and marked condensation of the vitreous with interdigitations (one
case). En face OCT imaging at the level of the retinal pigment epithelial zone
showed a hyporeflective, round, well-delineated mass. A peripheral poorly defined
hyperreflectivity with a central hyporeflectivity was observed at the level of
mid-retina, likely because of shadowing effect. The OCT-A reveals a dense
vascular network within the tumor. CONCLUSION: Retinal astrocytic hamartomas may
be well characterized by non-invasive imaging using spectral-domain OCT, en face
OCT, and OCT angiography. The OCT angiography seemed to show tumor vascularity,
which may represent dilated disorganized and anastomotic superficial and deep
plexus capillaries. The tumor is often unique, peripapillary, small in diameter,
and dome-shaped on spectral-domain OCT protruding into the vitreous cavity,
responsible for vitreous changes facing the lesion.
PMID- 27508424
TI - QUIESCENT HERPES SIMPLEX KERATITIS REACTIVATION AFTER INTRAVITREAL INJECTION OF
DEXAMETHASONE IMPLANT.
AB - PURPOSE: To report reactivation of herpes simplex virus keratitis after the
injection of dexamethasone implant (Ozurdex) and to raise the awareness of this
potentially vision threatening side effect. METHODS: A 90-year-old man presented
with ocular pain and tearing in the left eye 3 weeks after receiving a
dexamethasone implant (Ozurdex) for the treatment of macular edema associated
with branch retinal vein occlusion. The patient had a history of herpes simplex
virus keratitis that was quiescent for more than 30 years. RESULTS: Clinical
examination of the left eye showed arborizing epithelial ulcer with terminal
bulbs consistent with herpes simplex virus keratitis. CONCLUSION: Quiescent
herpes simplex virus keratitis can be reactivated after dexamethasone implant
(Ozurdex). Prophylactic antiviral therapy might be indicated in individuals who
have a high risk of recurrent herpetic disease.
PMID- 27508425
TI - Insights into the Nature of the Chemical Bonding in Thiophene-2-thiol from X-ray
Absorption Spectroscopy.
AB - Thiophenes are the simplest aromatic sulfur-containing compounds; they are
widespread in fossil fuels and a variety of natural products, and they have vital
roles in determining characteristic aromas that are important in food chemistry.
We used a combination of sulfur K-edge X-ray absorption spectroscopy and density
functional theory to investigate the chemical bonding in the novel sulfur
containing heterocycle thiophene-2-thiol. We show that solutions of thiophene-2
thiol contain significant quantities of the thione tautomer, which may be the
energetically preferred 5H-thiophene-2-thione or the more accessible 3H-thiophene
2-thione.
PMID- 27508426
TI - Learning Experiences of Nurses as Part of a European Union Project on
Complementary Therapies: A Multinational Qualitative Study.
AB - The objectives of this study were to investigate learning experiences of the
nurses who participated in transnational and multinational occupational training.
A qualitative descriptive methodology was used. Data are clustered into 3
categories "occupational training," "complementary care," and "intercultural
interaction." This research has revealed many insights into the transnational
training of nurses.
PMID- 27508427
TI - Stabilization of membrane necks by adhesive particles, substrate surfaces, and
constriction forces.
AB - Membrane remodelling processes involving the formation and fission of small buds
require the formation and closure of narrow membrane necks, both for biological
membranes and for model membranes such as lipid bilayers. The conditions required
for the stability of such necks are well understood in the context of budding of
vesicles with bilayer asymmetry and/or intramembrane domains. In many cases,
however, the necks form in the presence of an adhesive surface, such as a solid
particle or substrate, or the cellular cortex itself. Examples of such processes
in biological cells include endocytosis, exocytosis and phagocytosis of solid
particles, the formation of extracellular and outer membrane vesicles by
eukaryotic and prokaryotic cells, as well as the closure of the cleavage furrow
in cytokinesis. Here, we study the interplay of curvature elasticity, membrane
substrate adhesion, and constriction forces to obtain generalized stability
conditions for closed necks which we validate by numerical energy minimization.
We then explore the consequences of these stability conditions in several
experimentally accessible systems such as particle-filled membrane tubes,
supported lipid bilayers, giant plasma membrane vesicles, bacterial outer
membrane vesicles, and contractile rings around necks. At the end, we introduce
an intrinsic engulfment force that directly describes the interplay between
curvature elasticity and membrane-substrate adhesion.
PMID- 27508429
TI - Engineering platelets for tumour-targeting.
PMID- 27508428
TI - Antibacterial ability and osteogenic activity of porous Sr/Ag-containing TiO2
coatings.
AB - Implant-associated infection and poor osseointegration remains a major clinical
challenge in Ti-based implant materials. A versatile strategy to endow Ti-based
implants with long-term antibacterial ability as well as better osteogenic
activity is highly desirable for high quality implantation. Strontium (Sr) has
been shown to be a significant element to favor bone growth by promoting new bone
formation and inhibiting bone resorption. In this study, a novel duplex-treatment
technique encompassing magnetron sputtering with micro-arc oxidation is utilized
to fabricate porous Sr/Ag-containing TiO2 coatings loaded with different
concentrations of Ag and Sr. All coatings are porous with pore size less than 5
um. Ag is primarily distributed homogeneously inside the pores, and the
concentrations of Ag in Sr/Ag-containing TiO2 coatings with low and high Ag
contents are 0.40 at.% and 0.83 at.% respectively. We have demonstrated that this
kind of coating displays long-lasting antibacterial ability even up to 28 d due
to the incorporation of Ag. Further, Sr/Ag-containing TiO2 coatings with optimum
Ag and Sr contents revealed good cytocompatibility, enhanced osteoblast spreading
and osseointegration, which stemmed primarily from the synergistic effect exerted
by the porous surface topography and the bioactive element Sr. However, this
study has also identified, for the first time, that proper addition of Ag would
further facilitate osteogenic effects. Besides, Sr may be able to alleviate the
potential cytotoxic effect of excessive Ag. Thus, integration of optimum
functional elements Ag and Sr into Ti-based implant materials would be expected
to expedite osseointegration while simultaneously sustaining long-term
antibacterial activity, which would provide new insights for relevant fundamental
investigations and biomedical applications.
PMID- 27508430
TI - A Case of Mutism in Noncatatonic Schizophrenia Responding to Small Dose of
Fluvoxamine Addition to Clozapine.
PMID- 27508431
TI - New Insights into How Cholesterol and Unsaturation Control Lipid Domain
Formation.
PMID- 27508432
TI - Quantitative Localization Microscopy Reveals a Novel Organization of a High-Copy
Number Plasmid.
AB - The maintenance of high-copy number plasmids within bacteria had been commonly
thought to result from free diffusion and random segregation. Recent microscopy
experiments, however, observed high-copy number plasmids clustering into discrete
foci, which seemed to contradict this model, and hinted at an undiscovered active
mechanism, as often found in low-copy number plasmids. We recently investigated
the cellular organization of a ColE1-derivative plasmid in Escherichia coli
bacteria using quantitative superresolved microscopy based on single-molecule
localization in combination with single-molecule fluorescence in situ
hybridization (smFISH). We observed that many of the plasmids aggregated into
large clusters, although most of the plasmids were randomly distributed
throughout the bacteria, minus an excluded volume about the chromosomal DNA. Our
results indicate that neither of the previous models completely encompasses the
behavior of high-copy number plasmids. We also found many plasmids within the
chromosomal volume, providing further evidence that the nucleoid does not fully
exclude DNA and RNA.
PMID- 27508433
TI - Structure of an Intrinsically Disordered Stress Protein Alone and Bound to a
Membrane Surface.
AB - Dehydrins are a group of intrinsically disordered proteins that protect plants
from damage caused by drought, cold, and high salinity. Like other intrinsically
disordered proteins, dehydrins can gain structure when bound to a ligand.
Previous studies have shown that dehydrins are able to protect liposomes from
cold damage, but the interactions that drive membrane binding and the detailed
structure of the bound and unbound forms are not known. We use an ensemble
structure approach to generate models of a dehydrin known as K2 in the presence
and absence of sodium dodecyl sulfate micelles, and we docked the bound structure
to the micelle. The collection of residual dipolar coupling data, amide
protection factors, and paramagnetic relaxation enhancement distances, in
combination with chemical shifts and relaxation measurements, allows for
determining plausible structures that are not otherwise visible in time-averaged
structural data. The results show that in the bound structure, the conserved
lysines are important for membrane binding, whereas the flanking hydrophobic
residues play a lesser role. The unbound structure shows a high level of disorder
and an extended structure. We propose that the structural differences between
bound and unbound forms allow dehydrins to act as molecular shields in their
unbound state and as membrane protectants in their bound state. Unlike alpha
synuclein, the significant gain of alpha-helicity in K2 at low concentrations of
sodium dodecyl sulfate is not due to a decrease in the critical micelle
concentration. The study provides structural insight into how a disordered
protein can interact with a membrane surface.
PMID- 27508434
TI - RETRACTED: Protonation State-Dependent Communication in Cytochrome c Oxidase.
AB - Proton transfer in cytochrome c oxidase from the cellular inside to the binuclear
redox center (BNC) can occur through two distinct pathways, the D- and K
channels. For the protein to function as both redox enzyme and proton pump,
proton transfer out of either of the channels toward the BNC or into the protein
toward a proton loading site, and ultimately through the membrane, must be highly
regulated. The O->E intermediate of cytochrome c oxidase is the first redox state
in its catalytic cycle, where proton transfer through the K-channel, from K362 to
Y288 at the BNC, is important. Molecular dynamics simulations of this
intermediate with 16 different combinations of protonation states of key residues
in the D- and K-channel show the mutual impact of the two proton-conducting
channels to be protonation state-dependent. Strength as well as means of
communication, correlations in positions, or connections along the hydrogen
bonded network, change with the protonation state of the K-channel residue K362.
The conformational and hydrogen-bond dynamics of the D-channel residue N139
regulated by an interplay of protonation in the D-channel and K362. N139 thus
assumes a gating function by which proton passage through the D-channel toward
E286 is likely facilitated for states with protonated K362 and unprotonated E286,
which would in principle allow proton transfer to the BNC, but no proton pumping
until a proton has reached E286.
PMID- 27508435
TI - Effects of Temperature on Heteromeric Kv11.1a/1b and Kv11.3 Channels.
AB - Kv11.1 channels are crucial in cardiac physiology, and there is increasing
evidence of physiological roles of different Kv11 channels outside the heart. The
HERG (human Kv11.1a) channel has previously been shown to carry substantially
more current at elevated temperatures, and we have now comparably investigated
the temperature dependence of neuronal Kv11.3 channels and the more ubiquitous
heteromeric Kv11.1a/1b channels. Transiently expressed rat Kv11 channels were
studied at 21 degrees C, 30 degrees C, and 35 degrees C. At near-physiological
temperature, the maximal sustained outward current density was almost three times
the mean value obtained at room temperature for Kv11.1a/1b, and increased by
~150% for Kv11.3. For both channels, reduced inactivation contributed to the
current increase at higher temperature. Elevated temperature moved Kv11.1a/1b
isochronal activation curves to more negative potentials, but shifted the
potential of half-maximal Kv11.3 channel activation to more depolarized values
and reduced its voltage sensitivity. Thus, increased temperature stabilized the
open state over the closed state of Kv11.1a/1b channels and exerted the opposite
effect on Kv11.3 channel activation. Both Kv11 channels exhibited an overall high
temperature sensitivity of most gating parameters, with remarkably high Q10
factors of ~5 for the rate of Kv11.1a/1b activation. The Q10 factors for Kv11.3
gating were more uniform, but still higher for activation than for inactivation
kinetics. The results demonstrate that characteristic differences between
Kv11.1a/1b and Kv11.3 determined at room temperature do not necessarily apply to
physiological conditions. The data provided here can aid in the design of models
that will enhance our understanding of the role of Kv11 currents in excitable
cells.
PMID- 27508436
TI - Human Pulmonary Surfactant Protein SP-A1 Provides Maximal Efficiency of Lung
Interfacial Films.
AB - Pulmonary surfactant is a lipoprotein complex that reduces surface tension to
prevent alveolar collapse and contributes to the protection of the respiratory
surface from the entry of pathogens. Surfactant protein A (SP-A) is a hydrophilic
glycoprotein of the collectin family, and its main function is related to host
defense. However, previous studies have shown that SP-A also aids in the
formation and biophysical properties of pulmonary surfactant films at the air
water interface. Humans, unlike rodents, have two genes, SFTPA1 and SFTPA2. The
encoded proteins, SP-A1 and SP-A2, differ quantitatively or qualitatively in
function. It has been shown that both gene products are necessary for tubular
myelin formation, an extracellular structural form of lung surfactant. The goal
of this study was to investigate potential differences in the biophysical
properties of surfactants containing human SP-A1, SP-A2, or both. For this
purpose, we have studied for the first time, to our knowledge, the biophysical
properties of pulmonary surfactant from individual humanized transgenic mice
expressing human SP-A1, SP-A2, or both SP-A1 and SP-A2, in the captive bubble
surfactometer. We observed that pulmonary surfactant containing SP-A1 reaches
lower surface tension after postexpansion interfacial adsorption than surfactants
containing no SP-A or only SP-A2. Under interfacial compression-expansion cycling
conditions, surfactant films containing SP-A1 also performed better, particularly
with respect to the reorganization of the films that takes place during
compression. On the other hand, addition of recombinant SP-A1 to a surfactant
preparation reconstituted from the hydrophobic fraction of a porcine surfactant
made it more resistant to inhibition by serum than the addition of equivalent
amounts of SP-A2. We conclude that the presence of SP-A1 allows pulmonary
surfactant to adopt a particularly favorable structure with optimal biophysical
properties.
PMID- 27508437
TI - Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia.
AB - Diverse molecules induce general anesthesia with potency strongly correlated with
both their hydrophobicity and their effects on certain ion channels. We recently
observed that several n-alcohol anesthetics inhibit heterogeneity in plasma
membrane-derived vesicles by lowering the critical temperature (Tc) for phase
separation. Here, we exploit conditions that stabilize membrane heterogeneity to
further test the correlation between the anesthetic potency of n-alcohols and
effects on Tc. First, we show that hexadecanol acts oppositely to n-alcohol
anesthetics on membrane mixing and antagonizes ethanol-induced anesthesia in a
tadpole behavioral assay. Second, we show that two previously described
"intoxication reversers" raise Tc and counter ethanol's effects in vesicles,
mimicking the findings of previous electrophysiological and behavioral
measurements. Third, we find that elevated hydrostatic pressure, long known to
reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the
effect of butanol at relevant concentrations and pressures. Taken together, these
results demonstrate that DeltaTc predicts anesthetic potency for n-alcohols
better than hydrophobicity in a range of contexts, supporting a mechanistic role
for membrane heterogeneity in general anesthesia.
PMID- 27508438
TI - The Affinity of Cholesterol for Different Phospholipids Affects Lateral
Segregation in Bilayers.
AB - Saturated and unsaturated phospholipids (PLs) can segregate into lateral domains.
The preference of cholesterol for saturated acyl chains over monounsaturated, and
especially polyunsaturated ones, may also affect lateral segregation. Here we
have studied how cholesterol influenced the lateral segregation of saturated and
unsaturated PLs, for which cholesterol had a varying degree of affinity. The
fluorescence lifetime of trans-parinaric acid reported the formation of ordered
domains (gel or liquid-ordered (lo)) in bilayers composed of different
unsaturated phosphatidylcholines, and dipalmitoyl-phosphatidylcholine or n
palmitoyl-sphingomyelin, in the presence or absence of cholesterol. We observed
that cholesterol facilitated lateral segregations and the degree of facilitation
correlated with the relative affinity of cholesterol for the different PLs in the
bilayers. Differential scanning calorimetry and (2)H nuclear magnetic resonance
showed that cholesterol increased the thermostability of both the gel and lo
domains. Increased number of double bonds in the unsaturated PL increased the
order in the lo-domains, likely by enriching the ordered domains in saturated
lipids and cholesterol. This supported the conclusions from the trans-parinaric
acid experiments, and offers insight into how cholesterol facilitated lateral
segregation. In conclusion, the relative affinity of cholesterol for different
PLs appears to be an important determinant for the formation of ordered domains.
Our data suggests that knowledge of the affinity of cholesterol for the different
PLs in a bilayer allows prediction of the degree to which the sterol promotes lo
domain formation.
PMID- 27508439
TI - The Limiting Speed of the Bacterial Flagellar Motor.
AB - Recent experiments on the bacterial flagellar motor have shown that the structure
of this nanomachine, which drives locomotion in a wide range of bacterial
species, is more dynamic than previously believed. Specifically, the number of
active torque-generating complexes (stators) was shown to vary across applied
loads. This finding brings under scrutiny the experimental evidence reporting
that limiting (zero-torque) speed is independent of the number of active stators.
In this study, we propose that, contrary to previous assumptions, the maximum
speed of the motor increases as additional stators are recruited. This result
arises from our assumption that stators disengage from the motor for a
significant portion of their mechanochemical cycles at low loads. We show that
this assumption is consistent with current experimental evidence in chimeric
motors, as well as with the requirement that a processive motor driving a large
load via an elastic linkage must have a high duty ratio.
PMID- 27508441
TI - The Effect of Hematocrit on Platelet Adhesion: Experiments and Simulations.
AB - The volume fraction of red blood cells (RBCs) in a capillary affects the degree
to which platelets are promoted to marginate to near a vessel wall and form blood
clots. In this work we investigate the relationship between RBC hematocrit and
platelet adhesion activity. We perform experiments flowing blood samples through
a microfluidic channel coated with type 1 collagen and observe the rate at which
platelets adhere to the wall. We compare these results with three-dimensional
boundary integral simulations of a suspension of RBCs and platelets in a periodic
channel where platelets can adhere to the wall. In both cases, we find that the
rate of platelet adhesion varies greatly with the RBC hematocrit. We observe that
the relative decrease in platelet activity as hematocrit falls shows a similar
profile for simulation and experiment.
PMID- 27508440
TI - Association of Endophilin B1 with Cytoplasmic Vesicles.
AB - Endophilins are SH3- and BAR domain-containing proteins implicated in membrane
remodeling and vesicle formation. Endophilins A1 and A2 promote the budding of
endocytic vesicles from the plasma membrane, whereas endophilin B1 has been
implicated in vesicle budding from intracellular organelles, including the trans
Golgi network and late endosomes. We previously reported that endophilins A1 and
A2 exist almost exclusively as soluble dimers in the cytosol. Here, we present
results of fluorescence fluctuation spectroscopy analyses indicating that, in
contrast, the majority of endophilin B1 is present in multiple copies on small,
highly mobile cytoplasmic vesicles. Formation of these vesicles was enhanced by
overexpression of wild-type dynamin 2, but suppressed by expression of a
catalytically inactive dynamin 2 mutant. Using dual-color heterospecies partition
analysis, we identified the epidermal growth factor receptor on endophilin B1
vesicles. Moreover, a proportion of endophilin B1 vesicles also contained
caveolin, whereas clathrin was almost undetectable on those vesicles. These
results raise the possibility that endophilin B1 participates in dynamin 2
dependent formation of a population of transport vesicles distinct from those
generated by A-type endophilins.
PMID- 27508442
TI - Rheology of the Active Cell Cortex in Mitosis.
AB - The cell cortex is a key structure for the regulation of cell shape and tissue
organization. To reach a better understanding of the mechanics and dynamics of
the cortex, we study here HeLa cells in mitosis as a simple model system. In our
assay, single rounded cells are dynamically compressed between two parallel
plates. Our measurements indicate that the cortical layer is the dominant
mechanical element in mitosis as opposed to the cytoplasmic interior. To
characterize the time-dependent rheological response, we extract a complex
elastic modulus that characterizes the resistance of the cortex against area
dilation. In this way, we present a rheological characterization of the cortical
actomyosin network in the linear regime. Furthermore, we investigate the
influence of actin cross linkers and the impact of active prestress on
rheological behavior. Notably, we find that cell mechanics values in mitosis are
captured by a simple rheological model characterized by a single timescale on the
order of 10 s, which marks the onset of fluidity in the system.
PMID- 27508443
TI - Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet
Adhesion.
AB - Platelets bind to exposed vascular matrix at a wound site through a highly
specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes
von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it
becomes more stable as force is applied to it. After attaching to the wound site,
platelets generate cytoskeletal forces to compact and reinforce the hemostatic
plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of
cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure
the contractility of individual platelets on VWF. We found that a significant
proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an
unexpected finding given the widely held notion that platelet forces are
transmitted exclusively through its integrins. In particular, we found that the
interaction between GPIbalpha and the A1 domain of VWF mediates this force
transmission. We also demonstrate that the binding interaction between GPIbalpha
and filamin A is involved in force transmission. Furthermore, our studies suggest
that cytoskeletal forces acting through GPIbalpha are involved in maintaining
platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond
is able to transmit force, and uses this force to strengthen the bond through a
catch-bond mechanism. This finding expands our understanding of how platelets
attach to sites of vascular injury, describing a new, to the best of our
knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported
by internal forces produced by cytoskeletal tension.
PMID- 27508444
TI - Dopamine Receptor Signaling in MIN6 beta-Cells Revealed by Fluorescence
Fluctuation Spectroscopy.
AB - Insulin secretion defects are central to the development of type II diabetes
mellitus. Glucose stimulation of insulin secretion has been extensively studied,
but its regulation by other stimuli such as incretins and neurotransmitters is
not as well understood. We investigated the mechanisms underlying the inhibition
of insulin secretion by dopamine, which is synthesized in pancreatic beta-cells
from circulating L-dopa. Previous research has shown that this inhibition is
mediated primarily by activation of the dopamine receptor D3 subtype (DRD3), even
though both DRD2 and DRD3 are expressed in beta-cells. To understand this
dichotomy, we investigated the dynamic interactions between the dopamine receptor
subtypes and their G-proteins using two-color fluorescence fluctuation
spectroscopy (FFS) of mouse MIN6 beta-cells. We show that proper membrane
localization of exogenous G-proteins depends on both the Gbeta and Ggamma
subunits being overexpressed in the cell. Triple transfections of the dopamine
receptor subtype and Gbeta and Ggamma subunits, each labeled with a different
colored fluorescent protein (FP), yielded plasma membrane expression of all three
FPs and permitted an FFS evaluation of interactions between the dopamine
receptors and the Gbetagamma complex. Upon dopamine stimulation, we measured a
significant decrease in interactions between DRD3 and the Gbetagamma complex,
which is consistent with receptor activation. In contrast, dopamine stimulation
did not cause significant changes in the interactions between DRD2 and the
Gbetagamma complex. These results demonstrate that two-color FFS is a powerful
tool for measuring dynamic protein interactions in living cells, and show that
preferential DRD3 signaling in beta-cells occurs at the level of G-protein
release.
PMID- 27508445
TI - Phasor Analysis of Local ICS Detects Heterogeneity in Size and Number of
Intracellular Vesicles.
AB - Organelles represent the scale of organization immediately below that of the cell
itself, and their composition, size, and number are tailored to their function.
Monitoring the size and number of organelles in live cells is relevant for many
applications but can be challenging due to their highly heterogeneous properties.
Image correlation spectroscopy is a well-established analysis method capable of
extracting the average size and number of particles in images. However, when
image correlation spectroscopy is applied to a highly heterogeneous system, it
can fail to retrieve, from a single correlation function, the characteristic size
and the relative amount associated to each subspecies. Here, we describe a fast,
unbiased, and fit-free algorithm based on the phasor analysis of multiple local
image correlation functions, capable of mapping the sizes of elements contained
in a heterogeneous system. The method correctly provides the size and number of
separate subspecies, which otherwise would be hidden in the average properties of
a single correlation function. We apply the method to quantify the spatial and
temporal heterogeneity in the size and number of intracellular vesicles formed
after endocytosis in live cells.
PMID- 27508446
TI - Visualizing Flagella while Tracking Bacteria.
AB - A complete description of the swimming behavior of a bacterium requires
measurement of the displacement and orientation of the cell body together with a
description of the movement of the flagella. We rebuilt a tracking microscope so
that we could visualize flagellar filaments of tracked cells by fluorescence. We
studied Escherichia coli (cells of various lengths, including swarm cells),
Bacillus subtilis (wild-type and a mutant with fewer flagella), and a motile
Streptococcus (now Enterococcus). The run-and-tumble statistics were nearly the
same regardless of cell shape, length, and flagellation; however, swarm cells
rarely tumbled, and cells of Enterococcus tended to swim in loops when moving
slowly. There were events in which filaments underwent polymorphic
transformations but remained in bundles, leading to small deflections in
direction of travel. Tumble speeds were ~2/3 as large as run speeds, and the
rates of change of swimming direction while running or tumbling were smaller when
cells swam more rapidly. If a smaller fraction of filaments were involved in
tumbles, the tumble intervals were shorter and the angles between runs were
smaller.
PMID- 27508447
TI - Collective Chemotaxis through Noisy Multicellular Gradient Sensing.
AB - Collective cell migration in response to a chemical cue occurs in many biological
processes such as morphogenesis and cancer metastasis. Clusters of migratory
cells in these systems are capable of responding to gradients of <1% difference
in chemical concentration across a cell length. Multicellular systems are
extremely sensitive to their environment, and although the limits to
multicellular sensing are becoming known, how this information leads to coherent
migration remains poorly understood. We develop a computational model of
multicellular sensing and migration in which groups of cells collectively measure
noisy chemical gradients. The output of the sensing process is coupled to the
polarization of individual cells to model migratory behavior. Through the use of
numerical simulations, we find that larger clusters of cells detect the gradient
direction with higher precision and thus achieve stronger polarization bias, but
larger clusters also induce more drag on collective motion. The trade-off between
these two effects leads to an optimal cluster size for most efficient migration.
We discuss how our model could be validated using simple, phenomenological
experiments.
PMID- 27508448
TI - Mechanical Regulation of Three-Dimensional Epithelial Fold Pattern Formation in
the Mouse Oviduct.
AB - Epithelia exhibit various three-dimensional morphologies linked to organ function
in animals. However, the mechanisms of three-dimensional morphogenesis remain
elusive. The luminal epithelium of the mouse oviduct forms well-aligned straight
folds along the longitudinal direction of the tubes. Disruption of the Celsr1
gene, a planar cell polarity-related gene, causes ectopically branched folds.
Here, we evaluated the mechanical contributions of the epithelium to the fold
pattern formation. In the mutant oviduct, the epithelium was more intricate along
the longitudinal direction than in the wild-type, suggesting a higher ratio of
the longitudinal length of the epithelial layer to that of the surrounding smooth
muscle (SM) layer (L-Epi/SM ratio). Our mathematical modeling and computational
simulations suggested that the L-Epi/SM ratio could explain the differences in
fold branching between the two genotypes. Longitudinal epithelial tensions were
increased in well-aligned folds compared with those in disorganized folds both in
the simulations and in experimental estimations. Artificially increasing the
epithelial tensions suppressed the branching in simulations, suggesting that the
epithelial tensions can regulate fold patterning. The epithelial tensions could
be explained by the combination of line tensions along the epithelial cell-cell
boundaries with the polarized cell arrays observed in vivo. These results suggest
that the fold pattern is associated with the polarized cell array through the
longitudinal epithelial tension. Further simulations indicated that the L-Epi/SM
ratio could contribute to fold pattern diversity, suggesting that the L-Epi/SM
ratio is a critical parameter in the fold patterning in tubular organs.
PMID- 27508449
TI - Durotaxis in Nematode Caenorhabditis elegans.
AB - Durotaxis is a process where cells are able to sense the stiffness of substrates
and preferentially migrate toward stiffer regions. Here, we show that the 1-mm
long nematode, Caenorhabditis elegans are also able to detect the rigidity of
underlying substrates and always migrate to regions of higher stiffness. Our
results indicate that C. elegans are able to judiciously make a decision to stay
on stiffer regions. We found that the, undulation frequency, and wavelength of
worms, crawling on surfaces show nonmonotonic behavior with increasing stiffness.
A number of control experiments were also conducted to verify whether C. elegans
are really able to detect the rigidity of substrates or whether the migration to
stiffer regions is due to other factors already reported in the literature. As it
is known that bacteria and other single-celled organisms exhibit durotaxis toward
stiffer surfaces, we conjecture that durotaxis in C. elegans may be one of the
strategies developed to improve their chances of locating food.
PMID- 27508450
TI - Phenotypic Diversity Using Bimodal and Unimodal Expression of Stress Response
Proteins.
PMID- 27508451
TI - Peer Review and bioRxiv.
PMID- 27508453
TI - Retraction Notice.
AB - [This retracts the article on p. 9 in vol. 6, PMID: 24876696.].
PMID- 27508452
TI - Ultrafine Nb2O5 Nanocrystal Coating on Reduced Graphene Oxide as Anode Material
for High Performance Sodium Ion Battery.
AB - Ultrafine niobium oxide nanocrystals/reduced graphene oxide (Nb2O5 NCs/rGO) was
demonstrated as a promising anode material for sodium ion battery with high rate
performance and high cycle durability. Nb2O5 NCs/rGO was synthesized by
controllable hydrolysis of niobium ethoxide and followed by heat treatment at 450
degrees C in flowing forming gas. Transmission electron microscopy images showed
that Nb2O5 NCs with average particle size of 3 nm were uniformly deposited on rGO
sheets and voids among Nb2O5 NCs existed. The architecture of ultrafine Nb2O5 NCs
anchored on a highly conductive rGO network can not only enhance charge transfer
and buffer the volume change during sodiation/desodiation process but also
provide more active surface area for sodium ion storage, resulting in superior
rate and cycle performance. Ex situ XPS analysis revealed that the sodium ion
storage mechanism in Nb2O5 could be accompanied by Nb(5+)/Nb(4+) redox reaction
and the ultrafine Nb2O5 NCs provide more surface area to accomplish the redox
reaction.
PMID- 27508454
TI - American Telemedicine Association Guidelines for TeleICU Operations.
PMID- 27508456
TI - Errata: Hypertension and Diabetic Nephropathy.
PMID- 27508455
TI - Identification of Genes Involved in Breast Cancer Metastasis by Integrating
Protein-Protein Interaction Information with Expression Data.
AB - The selection of relevant genes for breast cancer metastasis is critical for the
treatment and prognosis of cancer patients. Although much effort has been devoted
to the gene selection procedures by use of different statistical analysis methods
or computational techniques, the interpretation of the variables in the resulting
survival models has been limited so far. This article proposes a new Random
Forest (RF)-based algorithm to identify important variables highly related with
breast cancer metastasis, which is based on the important scores of two variable
selection algorithms, including the mean decrease Gini (MDG) criteria of Random
Forest and the GeneRank algorithm with protein-protein interaction (PPI)
information. The new gene selection algorithm can be called PPIRF. The improved
prediction accuracy fully illustrated the reliability and high interpretability
of gene list selected by the PPIRF approach.
PMID- 27508457
TI - Bisphenol S Interacts with Catalase and Induces Oxidative Stress in Mouse Liver
and Renal Cells.
AB - Bisphenol S (BPS) is present in multitudinous consumer products and detected in
both food and water. It also has been a main substitute for bisphenol A (BPA) in
the food-packaging industry. Yet, the toxicity of BPS is not fully understood.
The present study of the toxicity of BPS was divided into two parts. First,
oxidative stress, cell viability, apoptosis level, and catalase (CAT) activity in
mouse hepatocytes and renal cells were investigated after BPS exposure. After 12
h of incubation with BPS, all of these parameters of hepatocytes and renal cells
changed by >15% as the concentration of BPS ranged from 0.1 to 1 mM. Second, the
direct interaction between BPS and CAT on the molecule level was investigated by
multiple spectral methods and molecular docking investigations. BPS changed the
structure and the activity of CAT through binding to the Gly 117 residue on the
substrate channel of the enzyme. The main binding forces were hydrogen bond and
hydrophobic force.
PMID- 27508458
TI - Pressure Profile Calculation with Mesh Ewald Methods.
AB - The importance of calculating pressure profiles across liquid interfaces is
increasingly gaining recognition, and efficient methods for the calculation of
long-range contributions are fundamental in addressing systems with a large
number of charges. Here, we show how to compute the local pressure contribution
for mesh-based Ewald methods, retaining the typical N log N scaling as a function
of the lattice nodes N. This is a considerable improvement on existing methods,
which include approximating the electrostatic contribution using a large cutoff
and the, much slower, Ewald calculation. As an application, we calculate the
contribution to the pressure profile across the water/vapor interface, coming
from different molecular layers, both including and removing the effect of
thermal capillary waves. We compare the total pressure profile with the one
obtained using the cutoff approximation for the calculation of the stresses,
showing that the stress distributions obtained using the Harasima and Irving
Kirkwood path are quite similar and shifted with respect to each other at most
0.05 nm.
PMID- 27508461
TI - Statistical Analysis of the Effectiveness of Seawalls and Coastal Forests in
Mitigating Tsunami Impacts in Iwate and Miyagi Prefectures.
AB - The Pacific coast of the Tohoku region of Japan experiences repeated tsunamis,
with the most recent events having occurred in 1896, 1933, 1960, and 2011. These
events have caused large loss of life and damage throughout the coastal region.
There is uncertainty about the degree to which seawalls reduce deaths and
building damage during tsunamis in Japan. On the one hand they provide physical
protection against tsunamis as long as they are not overtopped and do not fail.
On the other hand, the presence of a seawall may induce a false sense of
security, encouraging additional development behind the seawall and reducing
evacuation rates during an event. We analyze municipality-level and sub
municipality-level data on the impacts of the 1896, 1933, 1960, and 2011
tsunamis, finding that seawalls larger than 5 m in height generally have served a
protective role in these past events, reducing both death rates and the damage
rates of residential buildings. However, seawalls smaller than 5 m in height
appear to have encouraged development in vulnerable areas and exacerbated damage.
We also find that the extent of flooding is a critical factor in estimating both
death rates and building damage rates, suggesting that additional measures, such
as multiple lines of defense and elevating topography, may have significant
benefits in reducing the impacts of tsunamis. Moreover, the area of coastal
forests was found to be inversely related to death and destruction rates,
indicating that forests either mitigated the impacts of these tsunamis, or
displaced development that would otherwise have been damaged.
PMID- 27508459
TI - Binding Site Recognition and Docking Dynamics of a Single Electron Transport
Protein: Cytochrome c2.
AB - Small diffusible redox proteins facilitate electron transfer in respiration and
photosynthesis by alternately binding to their redox partners and integral
membrane proteins and exchanging electrons. Diffusive search, recognition,
binding, and unbinding of these proteins often amount to kinetic bottlenecks in
cellular energy conversion, but despite the availability of structures and
intense study, the physical mechanisms controlling redox partner interactions
remain largely unknown. The present molecular dynamics study provides an all-atom
description of the cytochrome c2-docked bc1 complex in Rhodobacter sphaeroides in
terms of an ensemble of favorable docking conformations and reveals an intricate
series of conformational changes that allow cytochrome c2 to recognize the bc1
complex and bind or unbind in a redox state-dependent manner. In particular, the
role of electron transfer in triggering a molecular switch and in altering water
mediated interface mobility, thereby strengthening and weakening complex
formation, is described. The results resolve long-standing discrepancies between
structural and functional data.
PMID- 27508462
TI - Comparison of experimental and theoretical quantum-state-selected integral cross
sections for the H2O(+) + H2 (D2) reactions in the collision energy range of 0.04
10.00 eV.
AB - To understand the dynamics of H3O(+) formation, we report a combined experimental
theoretical study of the rovibrationally state-selected ion-molecule reactions
H2O(+)(X(2)B1; v1(+)v2(+)v3(+); NKa(+)Kc(+)(+)) + H2 (D2) -> H3O(+) (H2DO(+)) + H
(D), where (v1(+)v2(+)v3(+)) = (000), (020), and (100) and NKa(+)Kc(+)(+) = 000,
111, and 211. Both quantum dynamics and quasi-classical trajectory calculations
were carried out on an accurate full-dimensional ab initio global potential
energy surface, which involves nine degrees of freedom. The theoretical results
are in good agreement with experimental measurements of the initial state
specific integral cross-sections for the formation of H3O(+) (H2DO(+)) and thus
provide valuable insights into the surprising rotational enhancement and
vibrational inhibition effects in these prototypical ion-molecule reactions that
play a key role in the interstellar generation of OH and H2O species.
PMID- 27508463
TI - A Global Synthesis of Jatropha Cultivation: Insights into Land Use Change and
Management Practices.
AB - Despite setbacks, interest in Jatropha cultivation remains high. This study
addressed the question to what extent Jatropha cultivation has replaced specific
vegetation and land use types and how the existing areas are managed. Major forms
of land use change and management practices were identified based on cluster
analysis of data from 106 interviewee's responses to a comprehensive global
survey. Of the 1.04 * 10(6) ha cultivated with Jatropha in 2011 40% were
established on land that was cleared of vegetation as a result of logging
activities unrelated to Jatropha cultivation, 34% was defined as unused, and the
remainder was attributable to areas previously used for crops or animal
husbandry. With the exception of croplands, these areas were dominated (90-98%)
by a few internationally active companies whose cultivation models were almost
exclusively based on outgrower schemes. Management practices were largely
extensive in nature (low mechanical input and infrequent use of fertilizers,
pesticides and herbicides), and also dominated by large projects. Broad surveys,
such as this, are useful in identifying general trends in this emerging global
industry, but detailed case studies, particularly of large projects, are needed
in order to draw more informed conclusions about the site-specific impacts of
Jatropha cultivation.
PMID- 27508464
TI - Discoveries of Biological Sciences and their implications for nursing practice.
PMID- 27508465
TI - Social representations of citizenship by inpatients: implications for hospital
care.
AB - OBJECTIVE: examine the social representations of citizenship by inpatients
receiving hospital care. METHOD: qualitative approach, using the Theory of Social
Representations as a framework, with 31 inpatients in the internal medicine
sector of a public university hospital. Semi-structured interviews were
conducted, whose data were submitted to the Alceste program, with application of
lexical analysis. RESULTS: patients understand their rights, and citizenship in
the care process is understood based on the right to health, to receive good care
from a technical and human standpoint. CONCLUSION: being well treated as a person
and the provision of technical-procedural care are rights of patients; the
absence of one or the other implies, therefore, lack of respect for their
citizenship.
PMID- 27508466
TI - Health practices: the view of the black elderly population in a terreiro
community.
AB - OBJECTIVE: to understand health practices of black, elderly people in a terreiro
community (community of followers of traditional African-Brazilian religions).
METHOD: qualitative descriptive study under the Black-African paradigm of
civilization constituted by the Black-African cultural complex and the
structuring elements of the African cosmovision. Semi-structured interviews were
carried out from July to September 2013, with six black older people from a
terreiro community in Porto Alegre, RS. RESULTS: thematic content analysis
resulted in the following categories: Ancestry; Belonging: the way to know and
practice health; Health knowledge and practices in terreiro communities; and
Complementarity: promoting health in the terreiro and traditional medicine and
its respective subcategories. CONCLUSION: the study understood the importance of
having a knowledge of the practices of African traditions in both the lifestyle
and health of the older black population to help with nursing planning and
interventions in response to their needs.
PMID- 27508467
TI - Cost of dressings for prevention of sacral pressure ulcers.
AB - OBJECTIVE: to identify costs of dressings to prevent sacral pressure ulcers in an
adult intensive care unit in Parana, Brazil. METHODS: secondary analysis study
with 25 patients admitted between October 2013 and March 2014, using transparent
polyurethane film (n=15) or hydrocolloid dressing (n=10) on the sacral region.
The cost of each intervention was based on the unit amount used in each type of
dressing, and its purchase price (transparent film = R$15.80, hydrocolloid
dressing = R$68.00). RESULTS: the mean cost/patient was R$23.17 for use of
transparent film and R$190.40 for use of hydrocolloid dressing. The main reason
for changing the dressing was detachment. CONCLUSION: the transparent film was
the most economically advantageous alternative to prevent sacral pressure ulcers
in critical care patients. However, additional studies should be carried out
including assessment of the effectiveness of both dressings.
PMID- 27508468
TI - Nursing care through the perception of hospitalized children.
AB - OBJECTIVE: to describe the perception of hospitalized children of school age, on
nursing care and understand what are, from their perspective, the best ways to
address it to when performing such care. METHOD: qualitative, descriptive,
exploratory research, with concepts of Vygotsky used as theoretical framework.
The data collection occurred through interviews mediated by drawings and was
performed with ten school children, with the interview later transcribed and
submitted to a thematic analysis. RESULTS: showed the importance of playing
during hospitalization, of a friendly and caring approach and providing
explanations regarding the performed procedures. CONCLUSION: nursing
professionals need to consider how the children would like to receive the care
being provided, so that their singularities are respected, characterizing nursing
actions according to a perspective of the whole human being.
PMID- 27508469
TI - Dialogue: network that intertwines the pedagogical relationship into the
practical-reflective teaching.
AB - OBJECTIVE: to understand how dialogue occurs in the pedagogical relation in the
practical reflective teaching in an undergraduate program in nursing. METHOD:
qualitative research, case study. Data collection was conducted from May 2013 to
September 2014 with eight professors of Nursing, by means of observation and
interviews. Data analysis followed the operational proposal constituted by the
exploratory stage and the interpretive stage. RESULTS: point the dialogue
established within the pedagogical relation as a challenge to be faced in
practical-reflective teaching, so professor and student build a relationship that
foster thought and action in the theoretical context and in the field of
practice. CONCLUSION: in establishing a dialogic-reflective tone in the
pedagogical relationship, the professor opens paths to new discoveries, enabling
the creation of teaching-learning spaces that stimulate autonomy, abilities, and
critical and reflective attitudes of students along their education.
PMID- 27508470
TI - Experiences with severe maternal morbidity: a qualitative study on the perception
of women.
AB - OBJECTIVE: to know and analyze the experiences of women who developed an episode
of Severe Maternal Morbidity. METHOD: this is a qualitative study, in which we
interviewed 16 women admitted to a tertiary level hospital, as a result of this
morbid state. We used content analysis in data processing. RESULTS: two
categories were identified: "Understanding maternal morbidity as a negative
presence" and "Moving ahead: on constant alert". The interviewees mentioned
negative aspects, such as treatment difficulties and hospitalization, feelings of
fear, concern for the fetus, frustration with the idealized pregnancy, trauma;
and positive aspects, such as learning and the expression of the divine will in
the experience of illness. CONCLUSION: effective care during the prenatal period,
delivery and postpartum period should provide adequate support for the prevention
and assistance in Severe Maternal Morbidity.
PMID- 27508471
TI - Analysis of obstetric care provided by the Mobile Emergency Care Service.
AB - OBJECTIVE: analyze the pertinence of calls made by obstetric users of the Mobile
Emergency Care Service (SAMU 192) of Botucatu-SP. METHOD: retrospective and
analytical research. All records of prehospital obstetric care delivered by the
SAMU 192 in 2012 were analyzed. To be considered responsive, calls should lead to
referral to a reference obstetric hospital or be classified with the colors red,
orange and yellow, according to risk criteria defined by the Ministry of Health.
RESULTS: considering the two outcomes evaluated: referral to a reference hospital
and risk criteria defined by the Ministry of Health, 6.7% and 75.6% of the calls
were not pertinent, respectively. There was no matching between outcomes, neither
variation between primiparas and multiparas as regards the call pertinence.
CONCLUSION: this study ratifies the need for implementing a risk classification
protocol in obstetrics, and support managers in the organization, qualification
and effective implementation of the Rede Cegonha.
PMID- 27508472
TI - Nurses' managerial knowledge in the hospital setting.
AB - OBJECTIVE: to analyze nurses' managerial skills in the hospital setting, their
perception of their own education and the relevance of training for their
professional practice. METHOD: qualitative study based on the dialectical
hermeneutics framework. Thirty-two nurses from three hospitals in the Brazilian
state of Minas Gerais contributed to the study by taking part in six focus
groups. Records were transcribed and three categories emerged from content
analysis. RESULTS: results evidenced the following managerial skills:
supervision, leadership, decision making, planning and organization, as well as
the relevance of education centers for their improvement and the continuing
development of the nurses' managerial skills. CONCLUSION: the authors believe
this investigation will contribute for the improvement of nurses' necessary
managerial skills and also to identify gaps in this area of their education.
PMID- 27508473
TI - Analysis of managerial and healthcare indicators after nursing personnel
upsizing.
AB - OBJECTIVE: analyze healthcare and managerial indicators after nursing personnel
upsizing. METHOD: a retrospective, descriptive study was conducted using data
from computer systems of a university hospital in southern Brazil. Healthcare and
managerial indicators related to the first half of 2013 and 2014 were
statistically analyzed. RESULTS: increases of 40.0% in the number of nurses and
16.0% in the number of nursing technicians led to reductions of 12.0% in the
number of sickness absences, 21.8% in positive balance for compensatory time off,
92.0% in paid overtime. Reductions of 75.0% in pressure ulcer rates, 10.5% in the
number of falls and 50.0% in infections due to indwelling catheter use were also
observed. CONCLUSION: nursing staff upsizing caused a positive impact on
managerial and healthcare indicators and helped qualify care and improve work
conditions for the nursing team.
PMID- 27508474
TI - Association of frailty in hospitalized and institutionalized elderly in the
community-dwelling.
AB - OBJECTIVE: to investigate the association between frailty with hospitalization
and institutionalization in a follow-up study of elderly residents. METHOD: the
follow-up study was performed in 2008 and 2013 with elderly of both genders, aged
65 years and older who were living in the community-dwelling. The sampling
procedure performed was probabilistic, with dual-stage clustering. In 2008, 515
elderly people were interviewed and, in 2013, 262. We used the socioeconomic and
demographic data, self-reported morbidity, specific data of hospitalization and
institutionalization. Frailty was measured by the Edmonton Frail Scale (EFS), and
functional capacity through the Functional Independence Measure. RESULTS: we
found the mean gross EFS score was higher among resident elderly who were
hospitalized and institutionalized and was statistically significant in both
investigated years. CONCLUSION: the confirmation of association between frailty
and hospitalization and institutionalization reinforces the importance of the
subject, and highlights frailty as an important tool for risk estimates for these
adverse events.
PMID- 27508475
TI - Factor analysis of an instrument to measure the impact of disease on daily life.
AB - OBJECTIVE: to verify the structure of factors of an instrument to measure the
Heart Valve Disease Impact on Daily Life (IDCV) when applied to coronary artery
disease patients. METHOD: the study included 153 coronary artery disease patients
undergoing outpatient follow-up care. The IDCV structure of factors was initially
assessed by means of confirmatory factor analysis and, subsequently, by
exploratory factor analysis. The Varimax rotation method was used to estimate the
main components of analysis, eigenvalues greater than one for extraction of
factors, and factor loading greater than 0.40 for selection of items. Internal
consistency was estimated using Cronbach's alpha coefficient. RESULTS:
confirmatory factor analysis did not confirm the original structure of factors of
the IDCV. Exploratory factor analysis showed three dimensions, which together
explained 78% of the measurement variance. CONCLUSION: future studies with
expansion of case selection are necessary to confirm the IDCV new structure of
factors.
PMID- 27508476
TI - Validation to Portuguese of the Debriefing Experience Scale.
AB - OBJECTIVE: to translate and validate to Portuguese the Debriefing Experience
Scale jointly with individuals that used high-fidelity simulation in learning.
METHOD: methodological and exploratory study for an instrument translation and
validation. For the validation process, the event "III Workshop Brazil -
Portugal: Care Delivery to Critical Patients" was created. RESULTS: 103 nurses
attended. Validity and reliability of the scale, the correlation pattern among
variables, the sampling adequacy test, and the sphericity test showed good
results. Since there was no relationship among the groups established in the
exploratory factor analysis, the option was to follow the division established by
the original version. CONCLUSION: the version of the instrument was called Escala
de Experiencia com o Debriefing. The results showed good psychometric properties
and a good potential for use. However, further studies will contribute to
consolidate the validity of the scale and strengthen its potential use.
PMID- 27508477
TI - Fasting of less than eight hours in urgent and emergency surgeries versus
complication.
AB - OBJECTIVE: to verify the occurrence of intraoperative and postoperative
complications in patients undergoing urgent and emergency surgical procedures
between January and December 2012, with fasting time of less than 8 hours.
METHOD: a quantitative study was conducted, of the retrospective cohort type,
through the analysis of medical records. RESULTS: we included 181 records of
patients undergoing surgical procedures with average duration of 59.4 minutes.
Fractures correction surgeries stood out, totalling 32% of cases. We observed
complications in 36 patients (19.9%), vomiting being the most prevalent (47.2%);
followed by nausea (16.7%); need for blood transfusion (13.9%); surgical site
infection (11.1%); and death (11.1%). The average fasting time was 133.5 minutes.
The fasting time showed no statistically significant correlation with the
complications investigated. CONCLUSION: intraoperative and postoperative
complications were associated with the clinical conditions of the patients and
not with the fasting time.
PMID- 27508478
TI - Technology-dependent children and the demand for pharmaceutical care.
AB - OBJECTIVE: to understand the experience of mothers of technology-dependent
children as regards pharmaceutical care. METHOD: this was a qualitative,
descriptive-exploratory study developed based on open interviews using a
structured characterization tool, and applied during home visits to 12 mothers
caring for technology-dependent children. The data was submitted to inductive
content analysis. RESULTS: this study is split into two themes: (i) maternal
overload during pharmaceutical care, demonstrating the need to administer drugs
continuously and the repercussions of this exhaustive care on the caregivers;
(ii) the ease or difficulty of access to the medicines required, showing informal
strategies and support networks. CONCLUSION: pharmaceutical care is a daily
challenge expressed in maternal overload and difficulty accessing the drugs, made
worse by failures in the care network and coordinated care.
PMID- 27508479
TI - Prevention and monitoring of delirium in older adults: an educational
intervention.
AB - OBJECTIVE: to conduct an educational intervention with the nursing team members
of an intensive care unit (ICU), aiming to increase knowledge and to introduce
improvements in their practices regarding prevention and monitoring of delirium
in older patients. METHOD: this is an action research, in which workshops were
conducted with eleven nurses and a nursing technician from an ICU unit in
Salvador, Bahia, Brazil. RESULTS: ten problems regarding nursing practices for
prevention and monitoring of delirium were identified. Educational, practical,
technical, and managerial actions were planned, involving cross-sector
connections for planning ways to solve these problems. The groups reported
significant changes in the practices, with the implementation of drug-free
measures for preventing and managing the situation. CONCLUSION: the educational
intervention contributed to improve the nursing practices in the ICU unit
studied, and it also favored the development of critical thinking about the
problems mentioned, thus enabling permanent review of offered treatments.
PMID- 27508480
TI - Concepts and practices of teaching and exercise of leadership in Nursing.
AB - OBJECTIVE: to identify, describe and analyze characteristics of leadership, head
nurses and participants in the teaching-learning process of leadership in
Nursing, according to nurse professors who performed studies on this theme and
taught such content between 1972 and 1994 in nursing schools of the state of Sao
Paulo, southeastern Brazil. METHODS: Thematic Oral History was used. A total of
four nurse professors were interviewed, whose reports were submitted to content
analysis. RESULTS: the following aspects were approached in this study: the
context in which students developed leadership, the influence of previous
experiences on leadership qualification, its attributes, the importance of
leadership, the value of teaching it, the possibilities of emancipation of a head
nurse, the repercussions of teaching leadership for one's professional life, the
relationships between qualification and job market, the aspects of teaching
qualification and students' characteristics. CONCLUSION: although not essential
for nursing qualification, leadership had a symbolic capital.
PMID- 27508481
TI - Stressors perceived by patients in the immediate postoperative of cardiac
surgery.
AB - OBJECTIVE: to investigate stressors perceived by patients in the immediate
postoperative of cardiac surgery and their association with sociodemographic and
clinical characteristics. METHOD: a prospective correlational study conducted in
a city in Sao Paulo, between August 2013 and December 2014. A non-probabilistic
sample included patients submitted to their first coronary artery bypass graft or
mitral valve surgery. The "Environmental Stressor Questionnaire" adapted to
Portuguese was used. RESULTS: 105 patients participated in the study. The item
"being thirsty" was evaluated as the most stressful and "the nursing staff member
does not introduce himself/herself by the name" as the least stressful. Among
sociodemographic and clinical variables (gender, age, type and time of surgery,
pain, intubation time, use of psychotropic medications and length of stay in the
intensive care unit), only pain presented a significant association with the
stressors. CONCLUSION: knowing stressors can help implement practices associated
with their reduction, favoring patients' recovery.
PMID- 27508482
TI - Quality of working life of call-center workers.
AB - OBJECTIVE: to analyze the profile and quality of working life (QWL) of call
center workers. METHOD: quantitative research, conducted in one call-center of
the city of Sao Jose do Rio Preto - SP, using the QVP-35 questionnaire. RESULTS:
profile was composed by: 80.2% women; 66.3% were single, with high school diploma
and 6 hours of daily working hours; mean age of 28 years; 92.9% had only one job
with mean working experience of 3 years. Positive aspects of QWL: intrinsic
motivation, working ability, available resources and social support. Negative
aspects of QWL: workload and organizational support. CONCLUSION: the data
obtained indicate the need for better organization of call-center working
processes in the company and suggests other researches in this context.
PMID- 27508483
TI - Health care for patients with acute coronary syndrome according to quality
indicators.
AB - OBJECTIVE: to assess in-hospital care for patients with Acute Coronary Syndrome
according to quality indicators. METHOD: a longitudinal quantitative study was
performed between November 2012 and March 2013 with 94 patients, including
interviews and medical records. RESULTS: a total of 39.4% of patients had
unstable angina and 60.6% had myocardial infarction, of which 34% had ST segment
elevation. Patients with TIMI and GRACE scores higher than four and 140 (p<0.05)
respectively died. Admission to the intensive care unit totaled 2.1%; assessment
of left ventricular (LV) ejection fraction, 83.0%; ASA within 24 hours of
admission, 77.8%; statins, 72.7%; angiotensin-converting enzyme inhibitor, 62.8%;
anti-smoking counseling, 53.3%; and timely reperfusion, 62.5%. Of all
participants, 12.0% underwent an invasive strategy in 24h and 50.0% in 72h. Door
to-ECG time was 68.3+/-104.3 min and door-to-balloon time, 122+/-54.5 min.
CONCLUSIONS: health care protocols are required to standardize practice and
improve these indicators.
PMID- 27508484
TI - The communication process in Telenursing: integrative review.
AB - OBJECTIVE: to identify scientific evidence about the communication process in
Telenursing and analyze them. METHOD: integrative review performed in March 2014.
The search strategy, structured with the descriptors "telenursing" and
"communication", was implemented in the databases Medline, Bireme, Cinahl,
Scopus, Web of Science, Scielo, and Cochrane. RESULTS: ten studies were selected
after inclusion and exclusion criteria. The main challenges were: the clinical
condition of patients, the possibility for inadequate communication to cause
misconduct, the absence of visual references in interactions without video, and
difficulty understanding nonverbal communication. CONCLUSION: distance imposes
communicative barriers in all elements: sender, recipient and message; and in
both ways of transmission, verbal and nonverbal. The main difficulty is to
understand nonverbal communication. To properly behave in this context, nurses
must receive specific training to develop abilities and communication skills.
PMID- 27508485
TI - Impact of educational interventions in reducing diabetic complications: a
systematic review.
AB - OBJECTIVE: To identify in the literature evidence of the effectiveness and
efficacy of educational interventions in reducing metabolic and/or vascular
complications in adults with diabetes mellitus. METHOD: A systematic review
performed in LILACS, IBECS, CUMED, CINAHL and Medline databases and in the online
library SciELO with studies published from 2004 to 2014. RESULTS: Eleven studies
were included (5 randomized clinical trials and 6 quasi-experimental). We only
identified studies that analyzed vascular complications. CONCLUSION: Two clinical
trials demonstrated efficacy in reducing cardiovascular complications, of
cataract or retinopathy and nephropathy and all the quasi-experimental studies
showed effectiveness in reducing feet ulcers, peripheral neuropathy and
vasculopathy, and maintenance of kidney function.
PMID- 27508486
TI - Nursing diagnoses in patients with cerebral vascular accident: an integrative
review.
AB - OBJECTIVE: to verify the nursing diagnoses in patients affected by CVAs. METHOD:
this is an integrative review of the literature. The search was conducted on
LILACS, Scielo, Medline, CINAHL, and Scopus databases between February and March
2015, using the following keywords: "Enfermagem", "Acidente Vascular Cerebral",
"Diagnostico de Enfermagem"; and "Nursing", "Stroke", and "Nursing Diagnosis".
RESULTS: we found 9 articles published between 2009 and 2015; most of them were
Brazilian, cross-sectional, and exploratory, with a level of evidence of 6. The
evidence from the publications was classified as: "Evaluation and validation of
specific nursing diagnoses for subjects affected by CVAs" and "Application of the
nursing process on subjects affected by CVAs". CONCLUSION: we noticed the
publications focused on nursing diagnoses related to motor disorders, such as
risk of falls and impaired physical mobility. Domains regarding safety/protection
(domain 11) and sleep/resting (domain 4) were present in most evaluated
publications.
PMID- 27508487
TI - Public actions for control of breast cancer in Brazil: integrative review.
AB - OBJECTIVE: to analyze the scientific production on "breast cancer" in the period
from 2002 to 2013 and determine the public policies for screening and early
diagnosis of breast cancer. METHOD: this is an integrative literature review
conducted in the databases MEDLINE, LILACS, SciELO and Google Scholar. INCLUSION
CRITERIA: year and period of publication; availability of the full article;
publication in Brazil; and the cross-check of the keywords Breast Cancer, Primary
Health Care, Screening Programs, and Early Detection of Cancer. RESULTS: after
analysis, four thematic categories were obtained: breast self-examination,
clinical examination of breast, mammography, and factors that hinder the
adherence to the screening. CONCLUSION: health professionals have deficits of
knowledge on the area, indicating the need for other studies on the subject
addressed and greater investment in continuing education of professionals.
PMID- 27508488
TI - The Spiritism as therapy in the health care in the epilepsy.
AB - OBJECTIVE: to present a brief history of Spiritism, the vision of epilepsy by
Spiritism, and the potential of spirituality and religiosity care as
complementary and coadjutants treatments in epilepsy. METHOD: this is a brief
review about the impact of faith, spirituality, and religiosity, particularly the
Spiritism philosophy as complementary treatment to neurological disorders
(particularly focusing on epilepsy) and mental health. We conduct a review of
published articles (about religion/spirituality and epilepsy) in the Pubmed and
SciELO databases. CONCLUSION: the exercise of spirituality and religiosity can be
a positive coping strategy to support the traditional therapy of patients with
epilepsy and other neurological disorders. However, it is necessary to demystify
myths and beliefs about the epilepsy and improve knowledge about this important
health dimension among professionals, patients, and caregivers to explore their
full treatment and supportive potential.
PMID- 27508489
TI - Evaluation of Cardiovascular Risk Factors, Haematological and Biochemical
Parameters, and Serum Endocan Levels in Patients with Lichen Planus.
AB - BACKGROUND AND OBJECTIVE: The current study aimed to evaluate cardiovascular risk
factors, haematological and biochemical parameters, and serum endocan
concentrations in lichen planus (LP) patients. METHODS: This study was conducted
with 86 cases, including 43 LP patients and 43 healthy controls. Cardiovascular
risk factors, haematological and biochemical parameters, and endocan levels were
evaluated. RESULTS: The serum endocan concentrations of LP patients were not
significantly different from those of the healthy controls (p > 0.05). There were
no significant differences in the serum endocan levels according to
classification by cardiovascular risk factors and smoking history (p > 0.05). In
the LP group, white blood cell count, platelet distribution width and monocyte
count/high-density lipoprotein cholesterol ratios were significantly higher when
compared to the healthy controls (p < 0.05). The LP group had a lower mean
platelet volume than the healthy controls (p < 0.05). CONCLUSIONS: Serum endocan
levels did not change significantly in patients with LP, and there were
significant differences in haematological and biochemical parameters.
PMID- 27508490
TI - Metabolic Syndrome and Associated Factors in a Population-Based Sample of
Schoolchildren in Colombia: The FUPRECOL Study.
AB - BACKGROUND: In contrast to the definition of metabolic syndrome (MetS) in adults,
there is no standard definition of MetS in pediatric populations. We aimed at
assessing the differences in the prevalence of MetS in children and adolescents
aged 9-17 years using four different operational definitions for these age groups
and at examining the associated variables. METHODS: A total of 675 children and
1247 adolescents attending public schools in Bogota (54.4% girls; age range 9
17.9 years) were included. The prevalence of MetS was determined by the
definitions provided by the International Diabetes Federation (IDF) and three
published studies by Cook et al., de Ferranti et al., and Ford et al. In
addition, we further examined the associations between each definition of MetS in
the total sample and individual risk factors using binary logistic regression
models adjusted for gender, age, pubertal stage, weight status, and inflammation
in all participants. RESULTS: The prevalence of MetS was 0.3%, 6.3%, 7.8%, and
11.0% according to the definitions by IDF, Cook et al., Ford et al., and de
Ferranti et al., respectively. The most prevalent components were low high
density lipoprotein cholesterol and high triglyceride levels, whereas the least
prevalent components were higher waist circumference and hyperglycemia. Overall,
the prevalence of MetS was higher in obese than in non-obese schoolchildren.
CONCLUSIONS: MetS diagnoses in schoolchildren strongly depend on the definition
chosen. These findings may be relevant to health promotion efforts for Colombian
youth to develop prospective studies and to define which cut-offs are the best
indicators of future morbidity.
PMID- 27508491
TI - Anti-staphylococcal Activity of Injectable Nano Tigecycline/Chitosan-PRP
Composite Hydrogel Using Drosophila melanogaster Model for Infectious Wounds.
AB - Compared to the current treatment modalities, the use of an injectable hydrogel
system, loaded with antibiotic encapsulated nanoparticles for the purpose of
treating Staphylococcus aureus (S. aureus) chronic wound infections have several
advantages. These include adhesiveness to infection site, reduced frequency of
dressings, sustained drug release, inhibition of bacterial growth, and increased
healing. In the present work tigecycline nanoparticles were loaded into chitosan
platelet-rich plasma (PRP) hydrogel. The tigecycline nanoparticles (95 +/- 13 nm)
were synthesized through ionic cross-linking method using chitosan,
tripolyphosphate, and tigecycline and characterized by dynamic light scattering
(DLS), scanning electron microscope (SEM), and Fourier transform infrared
spectroscopy (FT-IR). The synthesized nanoparticles and activated PRP powder were
mixed with chitosan hydrogel to form a homogeneous gel. Rheology studies have
confirmed the shear thinning property, thermal stability, and injectability of
the prepared gel systems. The gel system was further assessed for its drug
release property and found that it was released in a sustained manner. Hemolysis
and blood-clotting assays demonstrated that the gel system was neither a
hemolysin nor a hamper to the clotting cascade. Cell viability results showed
that these nanoparticles were cyto-compatible. The bioactivity of PRP loaded
chitosan gel toward fibroblast cell line was studied using cell proliferation and
migration assay. In vitro antibacterial studies revealed that the gel system
inhibited bacterial growth to a great extent. The antibacterial activity was
further analyzed using ex vivo porcine skin assay. In vivo anti-Staphylococcal
activity of the prepared hydrogels was studied using a Drosophila melanogaster
infection model. The tigecycline and tigecycline nanoparticle incorporated
chitosan gel showed a significant antibacterial activity against S. aureus. Thus,
the gel system is an effective medium for antibiotic delivery and can be applied
on the infection sites to effectively forestall various skin infections caused by
S. aureus.
PMID- 27508492
TI - Diastereoselective B(C6F5)3-Catalyzed Reductive Carbocyclization of Unsaturated
Carbohydrates.
AB - A B(C6F5)3-catalyzed method for the selective conversion of unsaturated
carbohydrates to cyclopentanes and cyclopropanes is disclosed. Catalyst
activation of tertiary silanes generates the ion pair [(C6F5)3B-H][ROSi2] whose
components synergistically activate C-O bonds for diastereoselective C-C bond
formation. Sila-THF cations are invoked as key intermediates facilitating
carbocyclizations. Complex chiral synthons are thereby obtained in a single pot.
PMID- 27508493
TI - B-Cyanodicarba-closo-dodecaboranes: Facile Synthesis and Spectroscopic Features.
AB - B-Cyanodicarba-closo-dodecaboranes are a poorly explored class of compounds due
to their complex synthetic availability. Now, we report a fast, atom-efficient,
and high-yielding synthesis. We obtained the cyano derivatives by reacting B
iododicarba-closo-dodecaboranes with copper(I) cyanide under both palladium
catalysis and microwave irradiation. We successfully applied this method to 9
iodo-o-, 9-iodo-m-, and 2-iodo-p-dicarba-closo-dodecaborane, obtaining the
corresponding cyanides up to 89% isolated yield. The facile synthesis and
evaluation of their spectroscopic properties reported herein will pave the way to
exploring the chemistry and application of B-cyanodicarba-closo-dodecaborane
clusters in more detail.
PMID- 27508494
TI - Susceptibility to Childhood Pneumonia: A Genome-Wide Analysis.
AB - : Previous studies have indicated that in adult smokers, a history of childhood
pneumonia is associated with reduced lung function and chronic obstructive
pulmonary disease. There have been few previous investigations using genome-wide
association studies to investigate genetic predisposition to pneumonia. This
study aims to identify the genetic variants associated with the development of
pneumonia during childhood and over the course of the lifetime. Study subjects
included current and former smokers with and without chronic obstructive
pulmonary disease participating in the COPDGene Study. Pneumonia was defined by
subject self-report, with childhood pneumonia categorized as having the first
episode at <16 years. Genome-wide association studies for childhood pneumonia
(843 cases, 9,091 control subjects) and lifetime pneumonia (3,766 cases, 5,659
control subjects) were performed separately in non-Hispanic whites and African
Americans. Non-Hispanic white and African American populations were combined in
the meta-analysis. Top genetic variants from childhood pneumonia were assessed in
network analysis. No single-nucleotide polymorphisms reached genome-wide
significance, although we identified potential regions of interest. In the
childhood pneumonia analysis, this included variants in NGR1 (P = 6.3 * 10-8),
PAK6 (P = 3.3 * 10-7), and near MATN1 (P = 2.8 * 10-7). In the lifetime pneumonia
analysis, this included variants in LOC339862 (P = 8.7 * 10-7), RAPGEF2 (P = 8.4
* 10-7), PHACTR1 (P = 6.1 * 10-7), near PRR27 (P = 4.3 * 10-7), and near MCPH1 (P
= 2.7 * 10-7). Network analysis of the genes associated with childhood pneumonia
included top networks related to development, blood vessel morphogenesis, muscle
contraction, WNT signaling, DNA damage, apoptosis, inflammation, and immune
response (P <= 0.05). We have identified genes potentially associated with the
risk of pneumonia. Further research will be required to confirm these
associations and to determine biological mechanisms. CLINICAL TRIAL REGISTRATION:
NCT00608764.
PMID- 27508495
TI - A let-7-to-miR-125 MicroRNA Switch Regulates Neuronal Integrity and Lifespan in
Drosophila.
AB - Messenger RNAs (mRNAs) often contain binding sites for multiple, different
microRNAs (miRNAs). However, the biological significance of this feature is
unclear, since such co-targeting miRNAs could function coordinately,
independently, or redundantly with one another. Here, we show that two co
transcribed Drosophila miRNAs, let-7 and miR-125, non-redundantly regulate a
common target, the transcription factor Chronologically Inappropriate
Morphogenesis (Chinmo). We first characterize novel adult phenotypes associated
with loss of both let-7 and miR-125, which are derived from a common,
polycistronic transcript that also encodes a third miRNA, miR-100. Consistent
with the coordinate upregulation of all three miRNAs in aging flies, these
phenotypes include brain degeneration and shortened lifespan. However, transgenic
rescue analysis reveal separable roles for these miRNAs: adult miR-125 but not
let-7 mutant phenotypes are associated with ectopic Chinmo expression in adult
brains and are suppressed by chinmo reduction. In contrast, let-7 is
predominantly responsible for regulating chinmo during nervous system formation.
These results indicate that let-7 and miR-125 function during two distinct
stages, development and adulthood, rather than acting at the same time. These
different activities are facilitated by an increased rate of processing of let-7
during development and a lower rate of decay of the accumulated miR-125 in the
adult nervous system. Thus, this work not only establishes a key role for the
highly conserved miR-125 in aging. It also demonstrates that two co-transcribed
miRNAs function independently during distinct stages to regulate a common target,
raising the possibility that such biphasic control may be a general feature of
clustered miRNAs.
PMID- 27508496
TI - Interspecific Hybridization in Pilot Whales and Asymmetric Genetic Introgression
in Northern Globicephala melas under the Scenario of Global Warming.
AB - Pilot whales are two cetacean species (Globicephala melas and G. macrorhynchus)
whose distributions are correlated with water temperature and partially overlap
in some areas like the North Atlantic Ocean. In the context of global warming,
distribution range shifts are expected to occur in species affected by
temperature. Consequently, a northward displacement of the tropical pilot whale
G. macrorynchus is expected, eventually leading to increased secondary contact
areas and opportunities for interspecific hybridization. Here, we describe
genetic evidences of recurrent hybridization between pilot whales in northeast
Atlantic Ocean. Based on mitochondrial DNA sequences and microsatellite loci,
asymmetric introgression of G. macrorhynchus genes into G. melas was observed.
For the latter species, a significant correlation was found between historical
population growth rate estimates and paleotemperature oscillations. Introgressive
hybridization, current temperature increases and lower genetic variation in G.
melas suggest that this species could be at risk in its northern range. Under
increasing environmental and human-mediated stressors in the North Atlantic
Ocean, it seems recommendable to develop a conservation program for G. melas.
PMID- 27508498
TI - Short-Term Behavioural Responses of the Great Scallop Pecten maximus Exposed to
the Toxic Alga Alexandrium minutum Measured by Accelerometry and Passive
Acoustics.
AB - Harmful algal blooms produced by toxic dinoflagellates have increased worldwide,
impacting human health, the environment, and fisheries. Due to their potential
sensitivity (e.g., environmental changes), bivalves through their valve movements
can be monitored to detect harmful algal blooms. Methods that measure valve
activity require bivalve-attached sensors and usually connected cables to data
transfers, leading to stress animals and limit the use to sessile species. As a
non-intrusive and continuously deployable tool, passive acoustics could be an
effective approach to detecting harmful algal blooms in real time based on animal
sound production. This study aimed to detect reaction changes in the valve
movements of adult Pecten maximus exposed to the toxic dinoflagellate Alexandrium
minutum using both accelerometry and passive acoustic methods. Scallops were
experimentally exposed to three ecologically relevant concentrations of A.
minutum for 2 hours. The number of each type of valve movement and their sound
intensity, opening duration, and valve-opening amplitude were measured. Four
behaviours were identified: closures, expulsion, displacement, and swimming. The
response of P. maximus to A. minutum occurred rapidly at a high concentration.
The valve activity of P. maximus was different when exposed to high
concentrations (500 000 cells L-1) of A. minutum compared to the non-toxic
dinoflagellate Heterocapsa triquetra; the number of valve movements increased,
especially closure and expulsion, which were detected acoustically. Thus, this
study demonstrates the potential for acoustics and sound production changes in
the detection of harmful algal blooms. However, field trials and longer duration
experiments are required to provide further evidence for the use of acoustics as
a monitoring tool in the natural environment where several factors may interfere
with valve behaviours.
PMID- 27508497
TI - Discovery of a Series of Acridinones as Mechanism-Based Tubulin Assembly
Inhibitors with Anticancer Activity.
AB - Microtubules play critical roles in vital cell processes, including cell growth,
division, and migration. Microtubule-targeting small molecules are
chemotherapeutic agents that are widely used in the treatment of cancer. Many of
these compounds are structurally complex natural products (e.g., paclitaxel,
vinblastine, and vincristine) with multiple stereogenic centers. Because of the
scarcity of their natural sources and the difficulty of their partial or total
synthesis, as well as problems related to their bioavailability, toxicity, and
resistance, there is an urgent need for novel microtubule binding agents that are
effective for treating cancer but do not have these disadvantages. In the present
work, our lead discovery effort toward less structurally complex synthetic
compounds led to the discovery of a series of acridinones inspired by the
structure of podophyllotoxin, a natural product with important microtubule
assembly inhibitory activity, as novel mechanism-based tubulin assembly
inhibitors with potent anticancer properties and low toxicity. The compounds were
evaluated in vitro by wound healing assays employing the metastatic and triple
negative breast cancer cell line MDA-MB-231. Four compounds with IC50 values
between 0.294 and 1.7 MUM were identified. These compounds showed selective
cytotoxicity against MDA-MB-231 and DU-145 cancer cell lines and promoted cell
cycle arrest in G2/M phase and apoptosis. Consistent with molecular modeling
results, the acridinones inhibited tubulin assembly in in vitro polymerization
assays with IC50 values between 0.9 and 13 MUM. Their binding to the colchicine
binding site of tubulin was confirmed through competitive assays.
PMID- 27508499
TI - Quality Indicators but Not Admission Volumes of Neonatal Intensive Care Units Are
Effective in Reducing Mortality Rates of Preterm Infants.
AB - AIM: To investigate how two different strategies to form larger neonatal
intensive care units (NICU) impact neonatal mortality rates. METHODS: Cross
sectional study modeling admission volumes and mortality rates of 177,086 VLBW
infants aggregated into 862 NICUs. Cumulative 3-year data was abstracted from
Vermont Oxford Network. The model simulated a reduction in number of NICUs by
stepwise exclusion using either admission volume (VOL) or quality (QUAL) cut
offs. After randomly redirecting infants of excluded to remaining NICUs resulting
system mortality rates were calculated with and without adjusting for effects of
experience levels (EL) using published data to reflect effects of different team
to-patient exposure. RESULTS: The quality-based strategy is more effective in
reducing mortality; while VOL alone was not able to reduce system mortality, QUAL
already achieved a 5% improvement after reducing 8% of NICUs and redirecting 6%
of infants. Including "EL", a 5% improvement of mortality was achieved by
reducing 77% (VOL) vs. 7% (QUAL) of NICUs and redirecting 54% (VOL) vs. 5% (QUAL)
of VLBW infants, respectively. CONCLUSION: While a critical number of admissions
is needed to maintain skills this study emphasizes the importance of including
quality parameters to restructure neonatal care. The findings can be generalized
to other medical fields.
PMID- 27508500
TI - QTL Mapping in Three Rice Populations Uncovers Major Genomic Regions Associated
with African Rice Gall Midge Resistance.
AB - African rice gall midge (AfRGM) is one of the most destructive pests of irrigated
and lowland African ecologies. This study aimed to identify the quantitative
trait loci (QTL) associated with AfRGM pest incidence and resistance in three
independent bi-parental rice populations (ITA306xBW348-1, ITA306xTOG7106 and
ITA306xTOS14519), and to conduct meta QTL (mQTL) analysis to explore whether any
genomic regions are conserved across different genetic backgrounds. Composite
interval mapping (CIM) conducted on the three populations independently uncovered
a total of 28 QTLs associated with pest incidence (12) and pest severity (16).
The number of QTLs per population associated with AfRGM resistance varied from
three in the ITA306xBW348-1 population to eight in the ITA306xTOG7106 population.
Each QTL individually explained 1.3 to 34.1% of the phenotypic variance. The
major genomic region for AfRGM resistance had a LOD score and R2 of 60.0 and
34.1% respectively, and mapped at 111 cM on chromosome 4 (qAfrGM4) in the
ITA306xTOS14519 population. The meta-analysis reduced the number of QTLs from 28
to 17 mQTLs, each explaining 1.3 to 24.5% of phenotypic variance, and narrowed
the confidence intervals by 2.2 cM. There was only one minor effect mQTL on
chromosome 1 that was common in the TOS14519 and TOG7106 genetic backgrounds; all
other mQTLs were background specific. We are currently fine-mapping and
validating the major effect genomic region on chromosome 4 (qAfRGM4). This is the
first report in mapping the genomic regions associated with the AfRGM resistance,
and will be highly useful for rice breeders.
PMID- 27508501
TI - The Safety, Tolerability and Risks Associated with the Use of Newer Generation
Antidepressant Drugs: A Critical Review of the Literature.
AB - Newer generation antidepressant drugs (ADs) are widely used as the first line of
treatment for major depressive disorders and are considered to be safer than
tricyclic agents. In this critical review, we evaluated the literature on adverse
events, tolerability and safety of selective serotonin reuptake inhibitors,
serotonin noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone,
agomelatine, vilazodone, levomilnacipran and vortioxetine. Several side effects
are transient and may disappear after a few weeks following treatment initiation,
but potentially serious adverse events may persist or ensue later. They encompass
gastrointestinal symptoms (nausea, diarrhea, gastric bleeding, dyspepsia),
hepatotoxicity, weight gain and metabolic abnormalities, cardiovascular
disturbances (heart rate, QT interval prolongation, hypertension, orthostatic
hypotension), genitourinary symptoms (urinary retention, incontinence), sexual
dysfunction, hyponatremia, osteoporosis and risk of fractures, bleeding, central
nervous system disturbances (lowering of seizure threshold, extrapyramidal side
effects, cognitive disturbances), sweating, sleep disturbances, affective
disturbances (apathy, switches, paradoxical effects), ophthalmic manifestations
(glaucoma, cataract) and hyperprolactinemia. At times, such adverse events may
persist after drug discontinuation, yielding iatrogenic comorbidity. Other areas
of concern involve suicidality, safety in overdose, discontinuation syndromes,
risks during pregnancy and breast feeding, as well as risk of malignancies. Thus,
the rational selection of ADs should consider the potential benefits and risks,
likelihood of responsiveness to the treatment option and vulnerability to adverse
events. The findings of this review should alert the physician to carefully
review the appropriateness of AD prescription on an individual basis and to
consider alternative treatments if available.
PMID- 27508502
TI - Location Prediction Based on Transition Probability Matrices Constructing from
Sequential Rules for Spatial-Temporal K-Anonymity Dataset.
AB - Spatial-temporal k-anonymity has become a mainstream approach among techniques
for protection of users' privacy in location-based services (LBS) applications,
and has been applied to several variants such as LBS snapshot queries and
continuous queries. Analyzing large-scale spatial-temporal anonymity sets may
benefit several LBS applications. In this paper, we propose two location
prediction methods based on transition probability matrices constructing from
sequential rules for spatial-temporal k-anonymity dataset. First, we define
single-step sequential rules mined from sequential spatial-temporal k-anonymity
datasets generated from continuous LBS queries for multiple users. We then
construct transition probability matrices from mined single-step sequential
rules, and normalize the transition probabilities in the transition matrices.
Next, we regard a mobility model for an LBS requester as a stationary stochastic
process and compute the n-step transition probability matrices by raising the
normalized transition probability matrices to the power n. Furthermore, we
propose two location prediction methods: rough prediction and accurate
prediction. The former achieves the probabilities of arriving at target locations
along simple paths those include only current locations, target locations and
transition steps. By iteratively combining the probabilities for simple paths
with n steps and the probabilities for detailed paths with n-1 steps, the latter
method calculates transition probabilities for detailed paths with n steps from
current locations to target locations. Finally, we conduct extensive experiments,
and correctness and flexibility of our proposed algorithm have been verified.
PMID- 27508503
TI - Age and Sex Ratios in a High-Density Wild Red-Legged Partridge Population.
AB - The dynamics of a wild red-legged partridge population were examined over a 14
year period in Spain to identify patterns in age and sex ratios in relation to
weather parameters, and to assess the importance of these parameters in
population dynamics and management. The results gave age ratios of 1.07 (but 2.13
in July counts), juvenile sex ratios of 1.01 and adult sex ratios of 1.47.
Overall, 12% more females were hatched and female juvenile mortality was 7.3%
higher than in males. Sex differential mortality explains the 19.2% deficit in
adult females, which are more heavily predated than males during the breeding
period. Accordingly, age ratios are dependent on sex ratios and both are density
dependent. Over time, ratios and density changes appear to be influenced by
weather and management. When the habitat is well conserved, partridge population
dynamics can be explained by a causal chain: weather operates on net primary
production, thereby affecting partridge reproduction and predation and, as a
result, age and sex ratios in the October population. A reduction in the impact
of predation (i.e. the effects of ground predators on eggs, chicks and breeding
females) is the key factor to improve the conservation of partridge populations
and associated biological processes.
PMID- 27508504
TI - Family factors and health behaviour of thin adolescent boys and girls.
AB - AIM: The aim of this study was to examine prevalence of extreme thinness and
thinness in adolescent boys and girls and to study associations between family
factors, health behaviour and thinness in boys and girls. BACKGROUND: Extreme
thinness carries high health risks. The family and health behavioural factors
related to adolescent thinness have not been studied previously using a
nationally representative data. DESIGN: This is a cross-sectional quantitative
study. METHODS: The nationally representative data were obtained from the Finnish
School Health Promotion study conducted in 2013. The sample of this study
included 12-17 year old adolescents (n = 71,973) who were categorised as
extremely thin, thin and normal weight using international age and gender body
mass index (BMI) cut-off points for children and adolescents. Associations with
family factors and health behaviour were examined separately for boys and girls
using cross-tabulations, Chi-square test and multinomial logistic regression.
RESULTS: Thinness and extreme thinness were more common in girls than in boys.
Health behaviour, such as smoking and exercise, were associated with thinness and
extreme thinness in both genders. Regarding family factors; low maternal
education, family meal and parental knowledge of adolescents' friends and
whereabouts were associated with thinness and, or extreme thinness in both boys
and girls. However, there were gender differences in the associations.
CONCLUSIONS: It is important for healthcare professionals working with
adolescents to be aware of prevalence in thinness and aware of health behaviour
and family factors that are associated with thinness and extreme thinness in
adolescence.
PMID- 27508505
TI - Generation of a Scaffold-Free Three-Dimensional Liver Tissue via a Rapid Cell-to
Cell Click Assembly Process.
AB - There has been tremendous interest in constructing in vitro liver organ models
for a range of fundamental studies of cell signaling, metabolism, and infectious
diseases, and as a commercial system to evaluate therapeutic drug discovery
prioritization and toxicity. Although there has been progress toward studying two
dimensional hepatic function in vitro, there remain challenging obstacles to
generate rapid and efficient scaffold-free three-dimensional multiple cell line
coculture tissue models of liver. Herein, we develop and employ a strategy to
induce specific and stable cell-cell contacts among multiple hepatic cell lines
to generate 3D tissues through cell-surface engineering based on liposome
delivery and fusion to display bio-orthogonal functional groups from cell
membranes. We generate, for the first time, a three cell line coculture 3D liver
tissue model by assembling hepatocytes, hepatic endothelial cells, and hepatic
stellate cells via a rapid intercell click ligation process. We compare and
analyze the function of the superior 3D liver tissue chips with 2D coculture
monolayer by assessing mitochondrial metabolic activity and evaluating drug
toxicity.
PMID- 27508506
TI - VITRECTOMY FOR MACULAR RETINOSCHISIS WITHOUT A DETECTABLE OPTIC DISK PIT.
AB - PURPOSE: To evaluate the efficacy of vitrectomy in the treatment of macular
retinoschisis without a detectable optic disk pit. METHODS: This retrospective
interventional case series included eight patients with acquired, unilateral
macular retinoschisis with or without foveal detachment. Patients with an optic
disk pit, vitreomacular traction, or high myopia were excluded. Six of the eight
patients underwent vitrectomy with internal limiting membrane peeling and fluid
air exchange. The surgical outcome was evaluated in terms of the improvement in
the macular anatomy and the best-corrected visual acuity. RESULTS: During
vitrectomy, all the six eyes were confirmed to have preexisting posterior
vitreous detachment. Macular retinoschisis was resolved or reduced in all the six
eyes after vitrectomy. The mean central foveal thickness showed significant
improvement at the time of the patient's final visit after vitrectomy. The mean
best-corrected visual acuity was 20/52 before surgery and 20/31 at the final
visit. CONCLUSION: Vitrectomy might be effective for the treatment of macular
retinoschisis without an optic disk pit. Although clinically similar to optic pit
maculopathy except for the absence of pit, our intraoperative observations of the
posterior hyaloid membrane suggest that maculopathy without optic disk pit has a
distinct pathogenesis.
PMID- 27508507
TI - Anillin controls cleavage furrow formation in the course of asymmetric division
during mouse oocyte maturation.
AB - Anillin is a scaffold protein that recruits several proteins involved in cleavage
furrow formation during cytokinesis. The role of anilllin in symmetric cell
divisions in somatic cells has been intensively studied, yet its involvement in
cleavage furrow formation is still elusive. In this study, we investigated the
role of anillin in mammalian oocyte maturation and cytokinesis. We found that
anillin is localized around the nucleus during the oocyte germinal-vesicle stage,
and spreads to the cytoplasm after germinal vesicle breakdown. Thereafter,
anillin concentrates at the site of the cleavage furrow from anaphase I to
metaphase II. Disruption of anillin activity by microinjecting oocytes with
specific siRNAs resulted in a failure of polar body extrusion and asymmetric
division, and caused abnormal chromosome segregation during anaphase I.
Furthermore, pharmacological inhibition of myosin light chain using Y-27632 or ML
7 resulted in decreased anillin expression. Collectively, our data suggest that
anillin is an essential intracellular component that maintains the integrity of
asymmetric division in mouse oocytes. Mol. Reprod. Dev. 83: 792-801, 2016 (c)
2016 Wiley Periodicals, Inc.
PMID- 27508508
TI - Use of Acellular Dermal Matrix versus Latissimus Dorsi Flap for Breast
Reconstruction: Clinical and Patient-Reported Outcomes.
PMID- 27508509
TI - The Significance of Sessile Serrated Polyps in Inflammatory Bowel Disease.
AB - BACKGROUND: The significance of serrated lesions in inflammatory bowel disease
(IBD) remains unclear. We aim to characterize synchronous and metachronous
lesions in IBD patients with an index serrated polyp and compare them to sporadic
subjects with SSP. METHODS: Serrated lesions in patients with IBD were identified
from a pathology database and, after review, were reclassified as hyperplastic
(HP), sessile serrated (SSPs), or serrated polyps unclassifiable (SPU). RESULTS:
One hundred thirty-four IBD patients were found to have 147 serrated polyps at
index colonoscopy. SSPs were more likely to be located in the right colon: SSP
(76.0%), SPU (41.7%) and HP (27.8%); P = 0.002. Synchronous multifocal visible
dysplasia occurred more frequently in the SSP or SPU groups (44.5% and 66%)
compared to the HP group (12%); P = 0.031. Among 13 IBD patients with index SSP
followed over a median of 6 years, 61.5% developed metachronous visible dysplasia
or additional SSPs. Larger index SSP size was associated with higher risk of
developing subsequent visible dysplasia with a 10% increase for every 1 mm
increase in size (HR = 1.1; P = 0.028), but was not associated with developing
subsequent SSP (P = 0.50). The risk of subsequent SSP or visible dysplasia was no
different between the IBD and non-IBD groups, but there was a trend suggesting
SSP may be a marker of increased early risk of metachronous visible dysplasia in
IBD patients. CONCLUSIONS: IBD patients with an index SSP and SPU have a
heightened risk of synchronous multifocal visible dysplasia. Additionally, IBD
patients with SSP may be at risk of early metachronous visible dysplasia.
PMID- 27508511
TI - Hypertrophic Mesenteric Adipose Tissue May Play a Role in Atherogenesis in
Inflammatory Bowel Diseases.
AB - BACKGROUND: Adipokines released by the adipose tissue are known to play a role in
atherogenesis. The hypertrophic mesenteric fat in patients with inflammatory
bowel diseases (IBD) also produces adipokines that are considered to play a role
in intestinal inflammation. Whether they also contribute to accelerated
atherosclerosis in IBD is unknown. The aim of this study was to assess the role
of 2 adipokines, resistin and adiponectin, in IBD. METHODS: We previously
published data on 3 markers of cardiovascular risk, carotid intima-media
thickness, carotid-femoral pulse wave velocity, and lipoprotein-associated
phospholipase A2, in 44 patients with IBD and 44 controls matched for established
cardiovascular risk factors. In this study, we measured resistin and adiponectin
levels, and assessed their correlations with carotid intima-media thickness,
pulse wave velocity, and lipoprotein-associated phospholipase A2. RESULTS:
Resistin levels were significantly higher in patients with IBD (13.7 versus 10
ng/mL; P = 0.022), but there was no difference in adiponectin levels. Resistin
levels were significantly higher in patients with active disease compared with
those in remission (18.9 versus 11.3 ng/mL; P = 0.014). Adiponectin levels were
significantly lower in Crohn's disease compared with ulcerative colitis (6736.3
+/- 3105 versus 10,476.1 +/- 5575.7 ng/mL; P = 0.026). Adiponectin correlated
inversely with pulse wave velocity (rho = -0.434; P < 0.0005) and carotid intima
media thickness (rho = -0.255; P = 0.021). CONCLUSIONS: This is the first study
to suggest that adipokines produced by the hypertrophic mesenteric fat in IBD may
play a role not only in intestinal inflammation but also in atherogenesis.
Resistin has mainly pro-inflammatory properties, whereas adiponectin likely
exerts an angioprotective effect.
PMID- 27508510
TI - Increased Prevalence of Inflammatory Bowel Disease in Patients with Mutations in
Genes Encoding the Receptor Subunits for TGFbeta.
AB - BACKGROUND: TGFbeta is a multifunctional cytokine that is critical in regulating
mucosal immunity. Murine studies have revealed that disruption of canonical
TGFbeta signaling leads to systemic inflammation including colitis. Loeys-Dietz
syndrome (LDS) results from heterozygous mutations in the genes encoding the
subunits of the TGFbeta receptor. METHODS: All patients with confirmed mutations
in TGFBR1 or TGFBR2, seen in the Johns Hopkins Connective Tissue Disorders
clinic, were asked to participate in the study. Ninety-three consecutive patients
were enrolled, including 4 with inflammatory bowel disease (IBD). Using the
Illumina Immunochip array, we undertook an exploratory analysis to evaluate the
potential genetic risk factors that could predict which patients with LDS would
develop IBD. RESULTS: We report an increased prevalence of IBD in patients with
LDS types I and II. We describe the course of several patients. In this small
sample, the 3 whites with IBD had a genetic risk score in the top 6 highest
scores of patients evaluated. CONCLUSION: We report a 10-fold increase in the
prevalence of IBD in patients with LDS compared with the general population.
Onset of disease in 3 of the 4 patients was at less than 18 years, and the
clinical course in 2 of the 4 was severe with a poor response to traditional
medications. Further evaluation of the genetic risk score is needed to determine
whether it can predict which patients with LDS are most likely to develop IBD.
This case series of patients with LDS with IBD suggests that defective TGFbeta
signaling may have an influence on IBD risk.
PMID- 27508512
TI - A Systematic Review on Infliximab and Adalimumab Drug Monitoring: Levels,
Clinical Outcomes and Assays.
AB - BACKGROUND: Immunogenicity to therapeutic proteins has been linked to loss of
response by a large percentage of patients taking anti-tumor necrosis factor
alpha agents. Drug monitoring can be extremely useful, allowing physicians to
adjust the therapeutic scheme individually. This article aims to systematically
review the published data with respect to cutoff levels of infliximab (IFX) and
adalimumab (ADA) and relate them to the methodology adopted for quantification of
IFX and ADA levels and clinical outcomes. METHODS: The PubMed database was
searched to identify studies focusing on the association between IFX or ADA
cutoff levels and clinical outcomes in patients with inflammatory bowel disease.
RESULTS: Of the 1654 articles initially selected by queries, 20 were included. A
receiver operating characteristic curve analysis was performed to identify cutoff
levels of IFX or ADA that correlated with a clinical outcome, but only 6 studies
performed the same analysis for antidrug antibody levels. Cutoff levels were
different between studies. The methodology chosen for level quantifications,
clinical outcomes, and sample size and characteristics were also different.
Nevertheless, measurement of drug levels should be performed during maintenance,
and with loss of response, with persistent high levels of C-reactive protein, and
when mucosal lesions are still present. In these scenarios, drug and antidrug
levels were correlated with clinical outcomes. CONCLUSIONS: Concerning drug
levels monitoring any methodology is adequate. With respect to antidrug antibody
levels, it will be necessary to define a gold standard method or to establish
different cutoff levels for different methodologies.
PMID- 27508513
TI - Computed Tomography and Magnetic Resonance Enterography in Crohn's Disease:
Assessment of Radiologic Criteria and Endpoints for Clinical Practice and Trials.
AB - Early recognition of Crohn's disease with initiation of disease-modifying therapy
has emerged as a prominent inflammatory bowel disease management strategy.
Clinical practice and trials have often focused on patient symptoms, and more
recently, serologic tests, stool inflammatory markers, and/or endoscopic
inflammatory features for study entry criteria, treatment targets, disease
activity monitoring, and to assess therapeutic response. Unfortunately, patient
symptoms do not correlate well with biological disease activity, and endoscopy
potentially misses or underestimates disease extent and severity in small bowel
Crohn's disease. Computed tomography enterography and magnetic resonance
enterography (MRE) are potential tools to identify and quantify transmural
structural damage and disease activity in the small bowel. In this review, we
discuss the role of computed tomography enterography and MRE in disease
management algorithms in clinical practice. We also compare the currently
developed MRE-based scoring systems, their strengths and pitfalls, as well as the
role for MRE in clinical trials for Crohn's disease.
PMID- 27508515
TI - Does a Higher Prevalence for Primary Diagnosis of Crohn's Disease Involve the
Upper Gastrointestinal Tract?
PMID- 27508516
TI - Pediatric Inflammatory Bowel Disease and Hereditary Hemolytic Anemia: A
Retrospective Analysis.
PMID- 27508514
TI - Emerging Roles for Noncanonical NF-kappaB Signaling in the Modulation of
Inflammatory Bowel Disease Pathobiology.
AB - Crohn's disease and ulcerative colitis are common and debilitating manifestations
of inflammatory bowel disease (IBD). IBD is characterized by a radical imbalance
in the activation of proinflammatory and anti-inflammatory signaling pathways in
the gut. These pathways are controlled by NF-kappaB, which is a master regulator
of gene transcription. In IBD patients, NF-kappaB signaling is often dysregulated
resulting in overzealous inflammation. NF-kappaB activation occurs through 2
distinct pathways, defined as either canonical or noncanonical. Canonical NF
kappaB pathway activation is well studied in IBD and is associated with the
rapid, acute production of diverse proinflammatory mediators, such as COX-2, IL
1beta, and IL-6. In contrast to the canonical pathway, the noncanonical or
"alternative" NF-kappaB signaling cascade is tightly regulated and is responsible
for the production of highly specific chemokines that tend to be associated with
less acute, chronic inflammation. There is a relative paucity of literature
regarding all aspects of noncanonical NF-KB signaling. However, it is clear that
this alternative signaling pathway plays a considerable role in maintaining
immune system homeostasis and likely contributes significantly to the chronic
inflammation underlying IBD. Noncanonical NF-kappaB signaling may represent a
promising new direction in the search for therapeutic targets and biomarkers
associated with IBD. However, significant mechanistic insight is still required
to translate the current basic science findings into effective therapeutic
strategies.
PMID- 27508517
TI - Fortification of condiments with micronutrients in public health: from proof of
concept to scaling up.
AB - Fortification of condiments or seasonings may be useful for delivering
micronutrients if they are consumed consistently by most of the population, as
occurs in many countries. The World Health Organization, in collaboration with
the Micronutrient Initiative and the Sackler Institute for Nutrition Science at
the New York Academy of Sciences, convened a technical consultation on
"Fortification of Condiments and Seasonings with Vitamins and Minerals in Public
Health: from Proof of Concept to Scaling Up" to review the role of condiments and
seasonings in improving micronutrient status, as constituents of regular diets
and patterns of production and consumption worldwide. The consultation covered
aspects related to implementation, monitoring, evaluation, and legal frameworks
of fortification programs, as well as food safety and policy coherence for
condiment fortification in the context of other public health strategies. This
paper introduces the background and rationale of the technical consultation,
synopsizes the presentations, and provides a summary of the main considerations
proposed by the working groups.
PMID- 27508518
TI - Host-pathogen interactions of nontypeable Haemophilus influenzae: from commensal
to pathogen.
AB - Nontypeable Haemophilus influenzae (NTHi) is a commensal microbe often isolated
from the upper and lower respiratory tract. This bacterial species can cause
sinusitis, acute otitis media in preschool children, exacerbations in patients
suffering from chronic obstructive pulmonary disease, as well as conjunctivitis
and bacteremia. Since the introduction of a vaccine against H. influenzae
serotype b in the 1990s, the burden of H. influenzae-related infections has been
increasingly dominated by NTHi. Understanding the ability of NTHi to cause
infection is currently an expanding area of study. NTHi is able to exert
differential binding to the host tissue through the use of a broad range of
adhesins. NTHi survival in the host is multifaceted, that is, using virulence
factors involved in complement resistance, biofilm, modified immunoglobulin
responses, and, finally, formation and utilization of host proteins as a
secondary strategy of increasing the adhesive ability.
PMID- 27508519
TI - A Graph is Worth a Thousand Words: How Overconfidence and Graphical Disclosure of
Numerical Information Influence Financial Analysts Accuracy on Decision Making.
AB - Previous researches support that graphs are relevant decision aids to tasks
related to the interpretation of numerical information. Moreover, literature
shows that different types of graphical information can help or harm the accuracy
on decision making of accountants and financial analysts. We conducted a 4*2
mixed-design experiment to examine the effects of numerical information
disclosure on financial analysts' accuracy, and investigated the role of
overconfidence in decision making. Results show that compared to text, column
graph enhanced accuracy on decision making, followed by line graphs. No
difference was found between table and textual disclosure. Overconfidence harmed
accuracy, and both genders behaved overconfidently. Additionally, the type of
disclosure (text, table, line graph and column graph) did not affect the
overconfidence of individuals, providing evidence that overconfidence is a
personal trait. This study makes three contributions. First, it provides evidence
from a larger sample size (295) of financial analysts instead of a smaller sample
size of students that graphs are relevant decision aids to tasks related to the
interpretation of numerical information. Second, it uses the text as a baseline
comparison to test how different ways of information disclosure (line and column
graphs, and tables) can enhance understandability of information. Third, it
brings an internal factor to this process: overconfidence, a personal trait that
harms the decision-making process of individuals. At the end of this paper
several research paths are highlighted to further study the effect of internal
factors (personal traits) on financial analysts' accuracy on decision making
regarding numerical information presented in a graphical form. In addition, we
offer suggestions concerning some practical implications for professional
accountants, auditors, financial analysts and standard setters.
PMID- 27508520
TI - Extracting DNA from 'jaws': high yield and quality from archived tiger shark
(Galeocerdo cuvier) skeletal material.
AB - Archived specimens are highly valuable sources of DNA for retrospective
genetic/genomic analysis. However, often limited effort has been made to evaluate
and optimize extraction methods, which may be crucial for downstream
applications. Here, we assessed and optimized the usefulness of abundant archived
skeletal material from sharks as a source of DNA for temporal genomic studies.
Six different methods for DNA extraction, encompassing two different commercial
kits and three different protocols, were applied to material, so-called bio
swarf, from contemporary and archived jaws and vertebrae of tiger sharks
(Galeocerdo cuvier). Protocols were compared for DNA yield and quality using a
qPCR approach. For jaw swarf, all methods provided relatively high DNA yield and
quality, while large differences in yield between protocols were observed for
vertebrae. Similar results were obtained from samples of white shark (Carcharodon
carcharias). Application of the optimized methods to 38 museum and private angler
trophy specimens dating back to 1912 yielded sufficient DNA for downstream
genomic analysis for 68% of the samples. No clear relationships between age of
samples, DNA quality and quantity were observed, likely reflecting different
preparation and storage methods for the trophies. Trial sequencing of DNA capture
genomic libraries using 20 000 baits revealed that a significant proportion of
captured sequences were derived from tiger sharks. This study demonstrates that
archived shark jaws and vertebrae are potential high-yield sources of DNA for
genomic-scale analysis. It also highlights that even for similar tissue types, a
careful evaluation of extraction protocols can vastly improve DNA yield.
PMID- 27508521
TI - Differential expression of desaturase genes and changes in fatty acid composition
of Mortierella sp. AGED in response to environmental factors.
AB - BACKGROUND: Some oleaginous fungi can produce large amounts of polyunsaturated
fatty acids (PUFAs) which serve many physiological functions. Numerous
desaturases are critical for the synthesis of PUFAs. This study aimed to
investigate the regulation of lipid production and desaturase gene expression in
Mortierella sp. AGED in response to different environmental factors, and the
relationships between lipid production and desaturase gene expression. RESULTS:
The fatty acid composition and mRNA levels of desaturase genes were significantly
changed under low temperatures. With the exception of Delta5-desaturase, the
transcript levels of all desaturase genes increased at a temperature of 20
degrees C. Changes in content of lipid and PUFAs responding to low temperature
were consistent with desaturase gene expression. Time course studies on gene
expression showed that mRNA levels of four desaturase genes increased rapidly
after transferring the cells to low temperature. Ethanol (1.5% v/v) increased the
transcript levels of Delta9-, Delta6- and Delta5-desaturase genes significantly
and of Delta12-desaturase gene slightly. Different metal ions such as Ca2+ , Zn2+
and Fe3+ could stimulate PUFA synthesis and up-regulate desaturase gene
transcription, while Cu2+ inhibited desaturase gene expression and lipid
accumulation. CONCLUSION: This study should enable us to understand the
regulatory mechanism of desaturase gene expression and lipid synthesis. It is
helpful to improve PUFA productivity in Mortierella sp. AGED. (c) 2016 Society of
Chemical Industry.
PMID- 27508523
TI - Nitrous oxide-based versus nitrous oxide-free general anaesthesia and accidental
awareness during general anaesthesia in surgical patients.
AB - BACKGROUND: Accidental awareness during general anaesthesia (AAGA) is when a
patient unintentionally becomes conscious during a procedure performed with
general anaesthesia and subsequently has explicit recall of this event. Incidence
estimates for AAGA vary, with the most common estimate being one to two cases per
1000 general anaesthetics. Evidence linking nitrous oxide use and an increased
risk of AAGA has come from observational studies data but the literature is
contradictory, with some studies finding a protective effect of nitrous oxide.
OBJECTIVES: To assess the effect of general anaesthesia including nitrous oxide
on the risk of AAGA in patients aged five years and over. SEARCH METHODS: We
searched the following databases: Cochrane Central Register of Controlled Trials
(CENTRAL), MEDLINE, EMBASE and trial registers ((www.clinicaltrials.gov), the WHO
International Clinical Trials Registry Platform (www.who.int/ictrp/network/en/)
and Current Controlled Trials (www.isrctn.com/)) for eligible studies on December
9 2015. In addition, we conducted forward and backward citation searching using
key identified papers. SELECTION CRITERIA: We considered all randomized
controlled trials (RCTs), including quasi-randomized studies and cluster
randomized studies, of participants aged five years or older receiving general
anaesthesia for any type of surgery.We included trials in which participants
receiving general anaesthesia that included nitrous oxide for maintenance at a
concentration of at least 30% were compared with participants receiving no
nitrous oxide during general anaesthesia. The intervention group must have
received nitrous oxide in conjunction with an additional anaesthetic. We excluded
studies where the depth of anaesthesia differed between the study arms. For
inclusion in the review, studies needed to state in their methods that they
planned to assess AAGA. We defined this as when a patient becomes conscious
during a procedure performed with general anaesthesia and subsequently has
explicit recall of this event. DATA COLLECTION AND ANALYSIS: We used standard
methodological procedures expected by Cochrane to identify studies. We extracted
data and conducted 'Risk of bias' assessment using the Covidence database. MAIN
RESULTS: We included 15 studies. The total number of participants included in the
analyses was 3520. Most studies were small with fewer than 120 participants,
although two larger studies with 2012 and 671 participants were included. There
was considerable variation in many of the study characteristics, including the
anaesthetics used. The concentrations of nitrous oxide varied between 50% and
70%, and half of the studies used clinical signs and haemodynamic changes to
monitor depth of anaesthesia.As it was not possible to blind the anaesthetist to
the anaesthetic used, we rated all studies at high risk of performance bias and
we therefore downgraded the quality of evidence by one level for risk of bias
using the GRADE approach. Other types of bias were generally low, or were rated
unclear due to missing information.No studies were designed to measure AAGA as
the primary outcome, and were therefore statistically underpowered to answer this
review question. Despite the inclusion of 3520 participants, only three awareness
events were reported by two studies. In one study the event was due to technical
failure. Due to the rarity of the events, we did not consider it appropriate to
pool the data, and we therefore downgraded the quality of evidence by a further
level for imprecision using GRADE. AUTHORS' CONCLUSIONS: It is not possible to
draw any conclusions from this review. The included studies were mainly small
(fewer than 120 participants) and there were limited estimates of effect, with
only two studies reporting any events. We cannot therefore determine whether the
use of nitrous oxide in general anaesthesia increases, decreases or has no effect
on the risk of accidental awareness.
PMID- 27508524
TI - Effect of substituents on prediction of TLC retention of tetra-dentate Schiff
bases and their Copper(II) and Nickel(II) complexes.
AB - The objectives of this study were to gain insights into structure-retention
relationships and to propose the model to estimating their retention.
Chromatographic investigation of series of 36 Schiff bases and their copper(II)
and nickel(II) complexes was performed under both normal- and reverse-phase
conditions. Chemical structures of the compounds were characterized by molecular
descriptors which are calculated from the structure and related to the
chromatographic retention parameters by multiple linear regression analysis.
Effects of chelation on retention parameters of investigated compounds, under
normal- and reverse-phase chromatographic conditions, were analyzed by principal
component analysis, quantitative structure-retention relationship and
quantitative structure-activity relationship models were developed on the basis
of theoretical molecular descriptors, calculated exclusively from molecular
structure, and parameters of retention and lipophilicity.
PMID- 27508522
TI - N-terminal fragment of the type-B natriuretic peptide (NT-proBNP) contributes to
a simple new frailty score in patients with newly diagnosed multiple myeloma.
AB - Multiple myeloma (MM) patient frailty has been delineated primarily by age and
ECOG performance score (PS) and recently by the IMWG frailty score based on
functional status [Activity of Daily Living (ADL) and Instrumental-ADL scores],
comorbidities [Charlson-comorbidity-index (CCI)] and age. It was hypothesized
that N-terminal natriuretic peptide type B (NT-proBNP) might be both a more
convenient measure of frailty and a predictor of overall survival (OS). Three
hundred and fifty-one consecutive symptomatic MM patients who were seen at Mayo
Clinic within 30 days of diagnosis and who had blood stored were eligible. Data
from the first visit was abstracted and used to calculate an ADL, CCI, and
measure the NT-proBNP level. The best cutoff of NT-proBNP predicting OS was 300
ng/L. Variables predictive for OS were ECOG-PS, age, CCI, ADL, ISS, revised-ISS,
and NT-proBNP. On multivariate analysis age >=70, PS >=2, and NT-proBNP >=300
were independent predictors of survival. Patients were assigned a score of 1 for
each of these variables, creating stages I-IV with scores of 0-3 points,
respectively. The median OS from diagnosis was not reached, 58, 28, and 18 months
(P < 0.0001), respectively. This frailty risk schema was independent of initial
therapy and the revised-ISS. NT-proBNP is a useful predictor of survival
independent of age and PS. It is a widely available biomarker that could be added
to the panel of laboratory tests of newly diagnosed MM patients and serve as a
simple and objective tool of determining frailty in clinical practice. Am. J.
Hematol. 91:1129-1134, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27508526
TI - FY17-PDH-EVTest04 GodInput Impact of the Oxygen Defects1 FY17-PDH-EVTest04
Reduction Rates of Stearic AcidFY17-PDH-T04.
AB - Test New Article1 GodEarlyview.Publish-on-load testing.The role of the specific
physicochemical properties of ZrO2 phases on Ni/ZrO2 has been explored with
respect to the reduction of stearic acid. Conversion on pure m?ZrO2 is 1.3 times
more active than on t?ZrO2 , whereas Ni/m?ZrO2 is three times more active than
Ni/t?ZrO2 . Although the hydrodeoxygenation of stearic acid can be catalyzed
solely by Ni, the synergistic interaction between Ni and the ZrO2 support causes
the variations in the reaction rates. Adsorption of the carboxylic acid group on
an oxygen vacancy of ZrO2 and the abstraction of the ??hydrogen atom with the
elimination of the oxygen atom to produce a ketene is the key to enhance the
overall rate. The hydrogenated intermediate 1?octadecanol is in turn
decarbonylated to heptadecane with identical rates on all catalysts.
Decarbonylation of 1?octadecanol is concluded to be limited by the competitive
adsorption of reactants and intermediate. The substantially higher adsorption of
propionic acid demonstrated by IR spectroscopy and the higher reactivity to O2
exchange reactions with the more active catalyst indicate that the higher
concentration of active oxygen defects on m?ZrO2 compared to t?ZrO2 causes the
higher activity of Ni/m?ZrO2 .
PMID- 27508527
TI - Validation of the Accutrend Plus point-of-care triglyceride analyzer in horses,
ponies, and donkeys.
AB - OBJECTIVE: To assess the accuracy and reliability of a point-of-care (POC)
triglyceride analyzer and to establish reference intervals for blood
([TRIG]POC/WB ) and plasma triglyceride concentrations ([TRIG]POC/PL ) in horses,
ponies, and donkeys. DESIGN: Prospective study. SETTING: University teaching
hospital. ANIMALS: 120 adult healthy equids (78 horses and ponies, 42 donkeys)
and 79 equids suffering from hypertriglyceridemia (73 horses and ponies, 6
donkeys). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: [TRIG]POC/WB and
[TRIG]POC/PL were measured using a POC analyzer and plasma triglyceride
concentrations were measured using a standard laboratory assay ([TRIG]LAB/PL ).
Reference intervals were determined. Test accuracy was assessed by Bland-Altman
comparison of POC measurements with standard laboratory measurements and by
evaluating linearity of dilutional series. Test reliability was assessed by
repeated serial measurements. [TRIG]POC/WB and [TRIG]POC/PL were below the
analytic range of the POC assay (<0.8 mmol/L [<70 mg/dL]) in healthy horses and
ponies, whereas the reference intervals were 0.82-3.14 mmol/L (73-278 mg/dL) and
0.87-3.02 mmol/L (77-267 mg/dL), respectively, in donkeys. The POC analyzer
systematically overestimated triglyceride concentrations when compared to a
standard laboratory assay. The difference between [TRIG]POC/WB and [TRIG]POC/PL
was small and clinically negligible. The coefficient of variation of repeated
measures performed on the POC analyzer was below 10% for [TRIG]POC/WB and
[TRIG]POC/PL , both in horses and donkeys and at all concentration ranges.
CONCLUSIONS: The POC analyzer allows accurate and reliable measurement of
[TRIG]POC/WB and [TRIG]POC/PL in horses, ponies, and donkeys in clinical
settings. Assay-specific reference intervals should be determined for diagnosis
and clinical monitoring of hypertriglyceridemia in equids.
PMID- 27508525
TI - Prognostic significance of day 14 bone marrow evaluation in adults with
Philadelphia chromosome-negative acute lymphoblastic leukemia.
AB - BACKGROUND: The role of day 14 (D14) bone marrow (BM) assessment in detecting
increased blasts in patients undergoing induction for acute lymphoblastic
leukemia (ALL) is not well defined. METHODS: This study evaluated 389 adolescent
and adult patients with previously untreated Philadelphia chromosome-negative ALL
who received frontline induction chemotherapy and for whom a D14 BM assessment
was performed. RESULTS: A D14 BM blast proportion < 10% (including blast-free
aplastic BM) was observed in 319 patients (82%), 10% to 29% was observed in 31
patients (8%), and >=30% was observed in 39 patients (10%). The composite
complete remission (CR)/complete remission with inadequate platelet recovery
(CRp) rates for these groups were 99.7%, 87%, and 79%, respectively. The median
event-free survival (EFS) was 49, 33, and 9 months, respectively (P < .001). The
median overall survival (OS) was 88, 37, and 21 months, respectively (P < .001).
The D14 BM blast group was the only factor predictive for the achievement of
CR/CRp (P < .001). According to a multivariate analysis, the D14 BM blast group
was independently prognostic for both EFS (hazard ratio [HR], 1.44; 95%
confidence interval [CI], 1.12-1.85; P = .004) and OS (HR, 1.45; 95% CI, 1.14
1.85; P = .003). However, when minimal residual disease (MRD) assessment at the
time of CR was added to the model, the D14 BM blast group was no longer
prognostic for EFS or OS. CONCLUSIONS: An assessment of residual D14 BM blasts in
patients with ALL is highly predictive of the achievement of CR with induction
chemotherapy and of EFS and OS. However, the D14 BM blast assessment is less
prognostic of long-term outcomes when an MRD assessment is also available. Cancer
2016;122:3812-3820. (c) 2016 American Cancer Society.
PMID- 27508529
TI - ZODIAC of Diarrhea Management.
PMID- 27508528
TI - Ascorbate-dependent impact on cell-derived matrix in modulation of stiffness and
rejuvenation of infrapatellar fat derived stem cells toward chondrogenesis.
AB - Developing an in vitro microenvironment using cell-derived decellularized
extracellular matrix (dECM) is a promising approach to efficiently expand adult
stem cells for cartilage engineering and regeneration. Ascorbic acid serves as a
critical stimulus for cells to synthesize collagens, which constitute the major
component of dECM. In this study, we hypothesized that optimization of ascorbate
treatment would maximize the rejuvenation effect of dECM on expanded stem cells
from human infrapatellar fat pad in both proliferation and chondrogenic
differentiation. In the duration regimen study, we found that dECM without L
ascorbic acid phosphate (AA) treatment, exhibiting lower stiffness measured by
atomic force microscopy, yielded expanded cells with higher proliferation
capacity but lower chondrogenic potential when compared to those with varied
durations of AA treatment. dECM with 250 uM of AA treatment for 10 d had better
rejuvenation in chondrogenic capacity if the deposited cells were from passage 2
rather than passage 5, despite no significant difference in matrix stiffness. In
the dose regimen study, we found that dECMs deposited by varied concentrations of
AA yielded expanded cells with higher proliferation capacity despite lower
expression levels of stem cell related surface markers. Compared to cells
expanded on tissue culture polystyrene, those on dECM exhibited greater
chondrogenic potential, particularly for the dECMs with 50 uM and 250 uM of AA
treatment. With the supplementation of ethyl-3,4-dihydroxybenzoate (EDHB), an
inhibitor targeting procollagen synthesis, the dECM with 50 uM of AA treatment
exhibited a dramatic decrease in the rejuvenation effect of expanded cell
chondrogenic potential at both mRNA and protein levels despite no significant
difference in matrix stiffness. Defined AA treatments during matrix preparation
will benefit dECM-mediated stem cell engineering and future treatments for
cartilage defects.
PMID- 27508530
TI - Ready to Measure Impact? The Introduction of Rotavirus Vaccine in India.
PMID- 27508531
TI - Healthcare Interventions and Vaccines.
PMID- 27508532
TI - Rotavirus in India: Forty Years of Research.
AB - Rotavirus was first identified as a human pathogen just over 40 years ago, and
work on this pathogen in India started shortly thereafter. Subsequent studies
have confirmed its pre-eminent role in gastroenteritis in children in India.
Standardized surveillance has enabled the documentation of the high burden of
disease, and has demonstrated that there is considerable geographic and temporal
variation in strain circulation. Internationally licensed vaccines, vaccine
candidates based on indigenous strains and out-licensed strains have been tested
for safety, immunogenicity and efficacy; three vaccines are now licensed in India
and are used in the private sector. Public sector vaccination has begun, and it
will be path-breaking for Indian vaccinologists to measure impact of vaccine
introduction in terms of safety and effectiveness. So far, India has kept pace
with international epidemiologic and vaccine research on rotavirus, and these
efforts should continue.
PMID- 27508533
TI - Expanded Indian National Rotavirus Surveillance Network in the Context of
Rotavirus Vaccine Introduction.
AB - OBJECTIVE: To extend a nation-wide rotavirus surveillance network in India, and
to generate geographically representative data on rotaviral disease burden and
prevalent strains. DESIGN: Hospital-based surveillance. SETTING: A comprehensive
multicenter, multi-state hospital based surveillance network was established in a
phased manner involving 28 hospital sites across 17 states and two union
territories in India. PATIENTS: Cases of acute diarrhea among children below 5
years of age admitted in the participating hospitals. RESULTS: During the 28
month study period between September 2012 and December 2014, 11898 children were
enrolled and stool samples from 10207 children admitted with acute diarrhea were
tested; 39.6% were positive for rotavirus. Highest positivity was seen in Tanda
(60.4%) and Bhubaneswar (60.4%) followed by Midnapore (59.5%). Rotavirus
infection was seen more among children aged below 2 years with highest (46.7%)
positivity in the age group of 12-23 months. Cooler months of September to
February accounted for most of the rotavirus associated gastroenteritis, with
highest prevalence seen during December to February (56.4%). 64% of rotaviru
infected children had severe to very severe disease. G1 P[8] was the predominant
rotavirus strain (62.7%) during the surveillance period. CONCLUSION: The
surveillance data highlights the high rotaviral disease burden in India. The
network will continue to be a platform for monitoring the impact of the vaccine.
PMID- 27508534
TI - Rotavirus and other Diarrheal Disease in a Birth Cohort from Southern Indian
Community.
AB - OBJECTIVE: To describe the incidence, severity and etiology of diarrheal disease
in infants and young children residing in an urban slum community in Southern
India. SETTING: Three contiguous urban slums in Vellore, Tamil Nadu.
PARTICIPANTS: 452 children participating in a birth cohort study on diarrheal
disease; 373 completed three years of follow-up. OUTCOME MEASURES: Diarrheal
incidence (obtained by twice-weekly home visits) and severity (assessed by the
Vesikari scoring system), and etiological agents associated with diarrhea
(through examination of stool specimens by bacteriologic culture, rotavirus
enzyme immunoassay, PCR for norovirus and microscopy for parasites). RESULTS: A
total of 1856 diarrheal episodes were reported in 373 children. The overall
incidence rate of diarrhea was 1.66 episodes per child year for three years, with
2.76 episodes per child year in infancy. The incidence peaked during the months
of July and August. Severe diarrhea formed 8% of the total episodes. Rotavirus
was the most common pathogen detected, being identified in 18% of episodes. Good
hygiene status resulted in 33% protection against moderate-to-severe diarrhea.
CONCLUSIONS: This study highlights the burden of diarrheal disease and the
important etiological agents of childhood diarrhea in Southern India. Promotion
of hygienic behavior through health education may help reduce diarrheal incidence
in this and similar communities.
PMID- 27508535
TI - Rotavirus Infections in Children Vaccinated Against Rotavirus in Pune, Western
India.
AB - OBJECTIVE: To characterize rotavirus infections detected in rotavirus vaccinated
children hospitalized for acute gastroenteritis. DESIGN: Observational, hospital
based study. SETTING: Three hospitals in Pune, Western India. PARTICIPANTS:
Children aged <5 years hospitalized for acute gastroenteritis during 2013-14.
METHODS: Rotavirus capture ELISA was performed on all stool samples that were
collected from patients following informed consent from parents. VP7 and VP4
genes of rotavirus strains were genotyped by multiplex RT-PCR. Stool samples from
vaccinated children were tested for other enteric viruses. RESULTS: Among the 529
children, 53 were vaccinated with at least one dose of the rotavirus vaccine.
There was no difference in the mean (SD) (months) age of vaccinated [14.8 (10.6)]
and unvaccinated [14.4 (10.5)] children. Rotavirus positivity was significantly
higher (47%) in unvaccinated than in vaccinated (28.3%) children (P=0.01). Mean
Vesikari score and severe cases were significantly more in rotavirus positive
than in negative children within unvaccinated group (P<0.001), while these did
not differ within the vaccinated group. Rotavirus strain G1P[8] was identified as
the most prevalent strain in both, vaccinated (60%) and unvaccinated (72.8%)
groups. No association was found between mean Vesikari score and viral
coinfections. CONCLUSIONS: This study suggests decline in rotavirus positivity in
rotavirus-vaccinated children hospitalized for acute gastroenteritis and high
prevalence of G1P[8] and non-rotaviral co-infections in Pune, Western India.
PMID- 27508536
TI - Racecadotril in the Management of Rotavirus and Non-rotavirus Diarrhea in Under
five Children: Two Randomized, Double-blind, Placebo-controlled Trials.
AB - OBJECTIVE: To study the effect of racecadotril on reduction in the duration of
acute rotavirus and non-rotavirus diarrhea. DESIGN: Two randomized double-blind
placebo-controlled trials. SETTING: Community-based trial in an urban area in
Vellore, hospital-based trial at a secondary hospital in Vellore. PARTICIPANTS:
199 and 130 3-59 month old children in the community- and hospital-based trials,
respectively. METHODS: Racecadotril (1.5 mg/kg/dose, thrice a day for three days)
or placebo were given to manage acute diarrhea in both trials. MAIN OUTCOME
MEASURE: Median duration of diarrhea. RESULTS: Among 124 children completing the
hospital trial, the median duration of diarrhea was 25 h in both arms (P=0.5);
median total stool weight was 74 g/kg and 53.5 g/kg in racecadotril group and
placebo group, respectively (P=0.4); and average fluid intake per day was 3.6
mL/kg/h and 3mL/kg/h in racecadotril and placebo arms, respectively (P=0.3).
Among rotavirus-positive children, median duration of diarrhea was 26.9 h and
30.2 h in racecadotril and placebo arms, respectively (P=0.7). In the community,
196 completed the trial, the median duration of diarrhea was 2 days for both arms
(P=0.8) and rotavirus positive children had similar outcomes with median
diarrheal duration of 3 d in both arms (P=0.4). CONCLUSIONS: Treatment with
racecadotril did not reduce diarrheal duration, stool volume or the requirement
for fluid replacement in children with acute gastroenteritis, both with and
without rotavirus infection.
PMID- 27508537
TI - Rotavirus specific Salivary and Fecal IgA in Indian Children and Adults.
AB - OBJECTIVE: To compare serum, salivary and fecal IgA responses in infants and
adults following rotavirus vaccination. STUDY DESIGN: Laboratory testing of
samples from clinical trials. SETTING: Medical College Hospital. PARTICIPANTS: 13
healthy adult volunteers not given vaccine, 20 healthy adult volunteers given one
dose of bovine rotavirus tetravalent vaccine (Shantha Biotechnics), and 88
infants given 3 or 5 doses of Rotarix. OUTCOME MEASURES: Serum, salivary and
fecal IgA at one or more time points. METHODS: IgA antibodies were estimated in
serum, saliva and fecal samples by enzyme-linked immunosorbent assay, and
normalized to total IgA in saliva. RESULTS: In naturally infected adult
volunteers, comparing serum and salivary IgA showed significant positive
correlation (r=0.759; P=0.003). Of 20 vaccinated adults, complete samples showing
change were available for 10; among them there was a significant positive
correlation (P<0.05) between pre-vaccination serum and pre-vaccination salivary
IgA but not between post-vaccination serum and post-vaccination salivary IgA. Of
88 infants given 3 or 5 doses of vaccine, 13 had more than 4-fold IgA response in
serum, saliva and fecal samples, 6 had a 2-4 fold increases in all specimens.
There was weak correlation between seroconversion rates measured by serum and
salivary antibody responses. Salivary and stool assays were able to detect
seroconversion in a few children in whom there was no detectable response in
serum. CONCLUSIONS: Evaluation of multiple samples is useful for intensive
experimental study designs and may help improve our understanding of the
induction and dynamics of immune responses to rotavirus vaccination.
PMID- 27508538
TI - Burden of Rotavirus Diarrhea in Under five Indian Children.
AB - NEED AND PURPOSE: Rotavirus is the most common cause of severe diarrhea in
infants and young children worldwide. The burden of rotavirus diarrhea in Indian
children is not well established. The present study reviewed the epidemiology of
rotavirus diarrhea in hospitalized children and in the community, molecular
serotyping and under-five mortality caused by rotavirus diarrhea. METHODS:
Publications, reporting rotavirus diarrhea in Indian children, were retrieved
through a systematic search of databases including Medline, PubMed, IndMed,
websites of WHO, UNICEF, National Family Health Survey, Ministry of Health and
Family Welfare, and Government of India. Human studies in English language were
included. Age group selected was 0 month to 5 years. No restrictions were applied
in terms of study design and time frame. CONCLUSIONS: Stool sample positivity
varied from 4.6% in Kolkata to 89.8% in Manipur, among hospitalized children, and
from 4% in Delhi to 33.7% in Manipur in community. Most cases of rotavirus
diarrhea in India are caused by G1, G2, and G untypeable strains with distinct
regional variations. Rotavirus was identified as an etiological agent in 5.2 to
80.5% cases of nosocomial diarrhea. Data are lacking for rotavirus mortality.
PMID- 27508539
TI - Profile and Trends of Rotavirus Gastroenteritis in Under 5 children in India,
2012 - 2014, Preliminary Report of the Indian National Rotavirus Surveillance
Network.
AB - OBJECTIVE: To estimate the burden of rotavirus-associated gastroenteritis in
India. METHODS: Hospital based surveillance network was established, with
clinical evaluation and laboratory testing for rotavirus among children aged
below 5 years hospitalized with acute gastroenteritis. RESULTS: Between September
2012 and December 2014, stool samples from 10207 children were tested and
rotavirus was detected in 39.6% of cases. Infections were more commonly seen
among younger children (<2 years). Detection rates were higher during cooler
months of September February. Among rotavirus infected children, 64.0% had severe
or very severe disease. G1P[8] was the predominant rotavirus genotype (62.7%)
observed during the surveillance period. CONCLUSIONS: Surveillance data
highlights the high rotavirus disease burden and emphasizes the need for close
monitoring to reduce morbidity and mortality associated with rotavirus
gastroenteritis in India.
PMID- 27508540
TI - Interpretation of Rotavirus positivity Patterns Across India.
AB - OBJECTIVE: To analyze variation in rotavirus-positivity using simple alternative
statistical measures. METHODS: Hospital-based rotavirus surveillance among
children admitted with acute gastroenteritis between 2005 and 2009. Prevalence,
adjusted proportions and symmetrized index were calculated. RESULTS: Rotavirus
prevalence was 40% (range 37% - 44%). Adjusted proportion analysis revealed
higher level of deviation from annual prevalence in seasons (December to February
and September to November); age groups (<12 months and 12-23 months) and regions
(East and South). Analysis of symmetrized index revealed higher estimates of
variation in all years, except in 2006. CONCLUSIONS: Proposed statistical
measures are useful as refined measures to study extent of disease spread in
surveillance programmes, aiding evaluation of the load and pattern of disease
burden in different regions over time.
PMID- 27508541
TI - Rotavirus Diarrhea in Children Presenting to an Urban Hospital in Western Uttar
Pradesh, India.
AB - OBJECTIVE: To determine the proportion and clinical profile of rotavirus
associated diarrhea in children aged 6 months to 5 years. METHODS: Clinical
details and stool samples were collected from 254 children aged between 6 months
to 5 years presenting with acute diarrhea, irrespective of hydration status, to
the outpatient department or emergency room of a hospital in Meerut, Uttar
Pradesh, India. RESULTS: Rotavirus accounted for 26.3% (51 of 194) of diarrhea
cases overall, and 41.2% (14 of 34) in hospitalized children. Rotavirus infection
was associated with significantly longer duration [3.3 (1.4) d vs. 2.5 (1.1) d;
P=0.004) of diarrhea, and more chances of dehydration (OR 1.85; 95% CI 1.19,
3.57) as compared to non-rotavirus diarrhea. CONCLUSIONS: Rotavirus is a common
cause of acute diarrhea in under-five children, and is associated with a longer
duration and more chances of dehydration than non-rotavirus diarrhea.
PMID- 27508542
TI - Rotavirus Infection in Children with Acute Gastroenteritis in Aurangabad, Central
Maharashtra.
AB - OBJECTIVE: To determine the prevalence of rotavirus diarrhea and its genotypes in
children from Aurangabad, India. METHODS: Stool samples collected during 2012
2013 from 168 children, aged ?3 years, were tested by ELISA to detect rotavirus.
Rotavirus strains were genotyped by multiplex reverse-transcription polymerase
chain reaction. RESULTS: Stool samples from 20 (11.9%) children tested positive
for rotavirus. Rotavirus positivity was higher among the children aged 0-12
months than those in 13-24 and 25-36 months. Severity of disease was moderate in
both rotavirus-infected and uninfected children. Genotype G1P[8] combination was
detected predominantly in circulation. CONCLUSIONS: Rotavirus diarrhea was caused
mainly by G1P[8] strains during 2012-2013 in Aurangabad, Central Maharashtra,
India.
PMID- 27508543
TI - Leveraging the National Rotavirus Surveillance Network for Monitoring
Intussusception.
AB - OBJECTIVE: To assess feasibility of monitoring intussusception by hospitals
participating in the National Rotavirus Surveillance Network. METHODS:
Questionnaire-based survey in 28 hospitals. One hospital with electronic records
selected for detailed data analysis. RESULTS: There was 75% response to the
questionnaire. Few network hospitals were suitable for monitoring intussusception
in addition to ongoing activities, but there was at least one potential sentinel
hospital in each region. The hospital selected for detailed data analysis of
cases of intussusception reported an incidence rate of 112 per 100,000 child
years in infants. Over 90% of intussusceptions were managed without surgery.
CONCLUSIONS: Selection of sentinel hospitals for intussusception surveillance is
feasible and necessary, but will require training, increased awareness and
referral.
PMID- 27508544
TI - Direct Medical Costs in Children with Rotavirus and Non-rotavirus Diarrhea
Admitted to a Pediatric Intensive Care Unit and High Dependency Unit in Delhi.
AB - OBJECTIVE: To estimate direct medical costs of diarrheal hospitalization of
children <5 years admitted in pediatric intensive care unit (PICU) or high
dependency unit (HDU). METHODS: Analysis of medical records and hospital bills of
84 children during two time frames, 2005-08 and 2012-14. RESULTS: Direct medical
costs in PICU increased from INR 17,941 to INR 50,663 per child for rotavirus
diarrhea and INR 11,614 to INR 27,106 for non-rotavirus diarrhea, and in HDU from
approximately INR 5,800 to INR 10,500 per child for all-cause diarrhea between
the two time frames. CONCLUSIONS: Costs of PICU and HDU care are high and should
be included in cost-effectiveness analysis of vaccination.
PMID- 27508545
TI - Direct and Indirect Costs of Pediatric Gastroenteritis in Vellore, India.
AB - OBJECTIVE: To determine costs of pediatric gastroenteritis in out-patient and in
patient facilities. METHODS: Cross-sectional survey of children with acute
gastroenteritis attending out-patient clinic (n=30) or admitted in the ward
(n=30) for management in the Christian Medical College, Vellore, India from July
September 2014 to estimate direct (drugs, tests, consultation/hospitalization)
and indirect (travel, food, lost wages) costs associated with the episode.
RESULTS: Median direct and indirect costs were Rs 590 and Rs 190 for out-patient
management and Rs 7258 and Rs. 610 for hospitalization, constituting 1.1% and 11%
of median annual household income, respectively. CONCLUSIONS: Escalating
healthcare costs need tracking for evaluation of interventions.
PMID- 27508546
TI - Time trend Analysis of the Impact of Universal Rotavirus Vaccination in Brazil:
Evidence based Medicine Viewpoint.
PMID- 27508547
TI - Time trend Analysis of the Impact of Universal Rotavirus Vaccination in Brazil:
Immunization Experts Viewpoint.
PMID- 27508548
TI - Hospital-based Surveillance of Rotavirus Diarrhea among Under- five Children in
Chandigarh.
AB - In a prospective hospital-based surveillance of 958 under five children admitted
with acute gastroenteritis in Chandigarh (May 2011 to July 2012), 239 stool
samples were collected. Rotavirus antigen was detected in 18.8% of samples by
reverse transcriptase polymerase chain reaction. Genotypes G1P[8] (53.3%),
G12P[6] (15.6%) were prevalent, and G3 not detected.
PMID- 27508549
TI - Immunochromatography-based Diagnosis of Rotavirus Infection in Acute Diarrhea.
AB - Documentation of rotavirus diarrhea in a rural, resource-poor setting is a
difficult task. We analyzed stool samples of 103 children admitted for acute
diarrhea in a pediatric hospital in Bijnor, UP, India, using a simple bedside
immunochromatography kit. Rotavirus infection was detected in 47 out of total of
103 children (45.6%).
PMID- 27508550
TI - Association of Rotavirus Gastroenteritis with Histo-blood Group Antigens.
AB - Association of rotavirus gastroenteritis with histo-blood group antigens in
children younger than 5 years admitted with diarrhea (n=389) was studied.
Distribution of blood groups in rotavirus positive (n=96) and rotavirus negative
(n=51) diarrhea gastroenteritis cases did not show any susceptibility to any
blood group; blood group O seemed to be protective.
PMID- 27508551
TI - Recurrent Intussusception in an Infant.
PMID- 27508552
TI - Sudden Death Due to Coronary Blockade by Microfilaremia: An Autopsy Report.
AB - Extralymphatic filarial disease has varied clinical manifestations and is largely
underestimated worldwide. We report an autopsy case of extralymphatic filarial
disease with coronary and pulmonary circulations being involved and causing
sudden death. Such an isolated event is, perhaps, rare and has not been reported
so far to the best of our knowledge. Microfilaremia on autopsy may be easily
missed or overlooked due to unawareness. The present report emphasizes the
importance of extensive careful scrutiny of autopsy sections.
PMID- 27508859
TI - Type I Interferon-Mediated Induction of Antiviral Genes and Proteins Fails to
Protect Cells from the Cytopathic Effects of Sendai Virus Infection.
AB - Sendai virus (SeV), a murine paramyxovirus, has been used to study the induction
of type I interferon (IFN) subtypes in robust quantities. Few studies have
measured whether the IFN that SeV induces actually fulfills its intended purpose
of interfering with virus-mediated effects in the cells in which it is produced.
We determined the effects of IFN on SeV-mediated cytopathic effects (CPE) and the
ability of IFN to protect against virus infection. SeV-induced biologically
active IFN resulted in Jak/STAT activation and the production of a number of
interferon-stimulated genes (ISGs). However, these responses did not inhibit SeV
replication or CPE. This observation was not due to SeV effects on canonical IFN
signaling. Furthermore, pretreating cells with type I IFN and establishing an
antiviral state before infection did not mediate SeV effects. Therefore, the
induction of canonical IFN signaling pathways and ISGs does not always confer
protection against the IFN-inducing virus. Because type I IFNs are approved to
treat various infections, our findings suggest that typical markers of IFN
activity may not be indicative of a protective antiviral response and should not
be used alone to determine whether an antiviral state against a particular virus
is achieved.
PMID- 27508861
TI - Accessory liver lobe attached to the gallbladder wall preoperatively detected by
ultrasonography: A case report.
AB - INTRODUCTION: An accessory liver lobe is a rare developmental abnormality, which
is often not diagnosed preoperatively, and is usually detected incidentally
during abdominal surgery. This condition is often asymptomatic; here, we report
on a case where the accessory liver lobe was diagnosed preoperatively using
ultrasonography. CASE PRESENTATION: A 59-year-old woman presented to our hospital
with right upper abdominal pain. An abdominal ultrasonography indicated the
presence of gallbladder debris and an accessory liver lobe. She underwent
laparoscopic cholecystectomy and resection of the accessory liver lobe without
any complications. DISCUSSION: An accessory liver lobe is a rare anomaly of the
liver. It is typically asymptomatic and is detected incidentally during surgery
or autopsy in most cases. However, we diagnosed the accessory liver lobe using
ultrasonography. An accessory liver lobe can occasionally result in
complications, such as bleeding, portal vein obstruction, or malignant
transformation to hepatocellular carcinoma. CONCLUSION: An accessory liver lobe
should be resected to prevent complications and malignant transformation.
Ultrasonography is useful for preoperative diagnosis in cases with an accessory
liver lobe.
PMID- 27508860
TI - The effect of copper from water and food: changes of serum nonceruloplasmin
copper and brain's amyloid-beta in mice.
AB - Copper is an essential element and also produces adverse health consequences when
overloaded. Food and water are the main sources of copper intake, however few
studies have been conducted to investigate the difference between the ways of its
intake in water and food in animals. In this study, copper was fed to mice with
food as well as water (two groups: water and diet) for three months at
concentrations of 6, 15 and 30 ppm. The copper concentration in water was
adjusted for keeping the same amount during its intake in food. The experimental
studies show a slow growth rate, lower hepatic reduced glutathione
(GSH)/superoxide dismutase (SOD) activity and higher serum 'free' copper in the
water group. The brain's soluble amyloid-beta 1-42 (Abeta42) of the water group
was significantly higher than that of the diet group at the levels of 6 and 15
ppm. In conclusion, copper in the water group significantly increased the soluble
Abeta42 in the brain and the 'free' copper in the serum, decreased the growth
rate and hepatic GSH/SOD activity. The research studies carried out suggest that
the copper in water is more 'toxic' than copper in diet and may increase the risk
of Alzheimer's disease (AD).
PMID- 27508863
TI - Influence of wastewater treatment plant discharges on microplastic concentrations
in surface water.
AB - The abundance of microplastic particles in the marine environment is well
documented, but less is known about microplastics in the freshwater environment.
Wastewater treatment plants (WWTPs) may not effectively remove microplastics
allowing for their release to the freshwater environment. To investigate
concentration of microplastic in fresh water and the impact of WWTP effluent,
samples were collected upstream and downstream of four major municipal WWTPs on
the Raritan River, NJ. Microplastics were categorized into three quantitative
categories (500-2000 MUm, 250-500 MUm, 125-250 MUm), and one semi-quantitative
category (63-125 MUm). Then, microplastics were classified as primary
(manufactured in small size) or secondary (derived from larger plastics) based on
morphology. The concentration of microplastics in the 125-250 and 250-500 MUm
size categories significantly increased downstream of WWTP. The smaller size
classes, often not quantified in microplastic studies, were in high relative
abundance across sampling sites. While primary microplastics significantly
increased downstream of WWTP, secondary microplastic was the dominant type in the
quantitative size categories (66-88%). A moderate correlation between
microplastic and distance downstream was observed. These results have
implications for understanding the fate and transport of microplastics in the
freshwater environment.
PMID- 27508862
TI - Crimean Congo Hemorrhagic Fever Virus and Alkhurma (Alkhumra) Virus in Ticks in
Djibouti.
AB - Crimean Congo hemorrhagic fever virus and Alkhumra virus, not previously reported
in Djibouti, were detected among 141 (infection rate = 15.7 per 100, 95% CI: 13.4
18.1) tick pools from 81 (37%) cattle and 2 (infection rate = 0.2 per 100, 95%
CI: 0.0-0.7) tick pools from 2 (1%) cattle, respectively, collected at an
abattoir in 2010 and 2011.
PMID- 27508864
TI - Cell Metabolism Remembers Cheolho Cheong.
PMID- 27508865
TI - How Body Affects Brain.
AB - Studies show that physical exercise can affect a range of brain and cognitive
functions. However, little is known about the peripheral signals that initiate
these central changes. Moon et al. (2016) provide exciting new evidence that a
novel myokine, cathepsin B (CTSB), released with exercise is associated with
improved memory.
PMID- 27508866
TI - Colonic Macrophages "Remote Control" Adipose Tissue Inflammation and Insulin
Resistance.
AB - The early events linking diet-induced adipose tissue inflammation and insulin
resistance remain poorly understood. In this issue of Cell Metabolism, Kawano et
al. (2016) show that infiltration of colonic pro-inflammatory macrophages
orchestrated by the intestinal CCL2/CCR2 axis kick-starts this process during
high-fat-diet feeding.
PMID- 27508867
TI - When Hexokinase Gets that NAG-ing Feeling....
AB - Immune cell recognition of bacterial products usually occurs via specific pattern
recognition receptors, but new research recently published in Cell by Wolf et al.
(2016) demonstrates that the glycolytic enzyme hexokinase can act as an innate
immune sensor by binding to bacterial derived N-acetylglucosamine (NAG).
PMID- 27508868
TI - Empagliflozin's Fuel Hypothesis: Not so Soon.
AB - The EMPA-REG OUTCOME trial (Zinman et al., 2015) established cardioprotective
effects of empagliflozin in high-risk diabetic patients, but the underlying
mechanisms remain elusive. A recent hypothesis proposed that increased ketone
oxidation contributed to the effect, but several caveats indicate that the role
of myocardial ketone oxidation is far from clear.
PMID- 27508869
TI - Sex and Gender: Critical Variables in Pre-Clinical and Clinical Medical Research.
AB - In this Essay, we discuss the critical need to incorporate sex and gender in pre
clinical and clinical research to enhance our understanding of the mechanisms by
which metabolic processes differ by sex and gender. This knowledge will allow for
development of personalized medicine which will optimize therapies specific for
individuals.
PMID- 27508870
TI - Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0):
Recommendations for Standardized FDG-PET/CT Experiments in Humans.
AB - Human brown adipose tissue (BAT) presence, metabolic activity, and estimated mass
are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in
response to cold exposure in regions of the body expected to contain BAT, using
positron emission tomography combined with X-ray computed tomography (FDG
PET/CT). Efforts to describe the epidemiology and biology of human BAT are
hampered by diverse experimental practices, making it difficult to directly
compare results among laboratories. An expert panel was assembled by the National
Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to
discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT,
data analysis, and publication of results. This resulted in Brown Adipose
Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully
validated best practices at this time, panel recommendations are meant to enhance
comparability across experiments, but not to constrain experimental design or the
questions that can be asked.
PMID- 27508871
TI - Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein
Metabolism and Circulating Neutrophils.
AB - The development of LXR agonists for the treatment of coronary artery disease has
been challenged by undesirable properties in animal models. Here we show the
effects of an LXR agonist on lipid and lipoprotein metabolism and neutrophils in
human subjects. BMS-852927, a novel LXRbeta-selective compound, had favorable
profiles in animal models with a wide therapeutic index in cynomolgus monkeys and
mice. In healthy subjects and hypercholesterolemic patients, reverse cholesterol
transport pathways were induced similarly to that in animal models. However,
increased plasma and hepatic TG, plasma LDL-C, apoB, apoE, and CETP and decreased
circulating neutrophils were also evident. Furthermore, similar increases in LDL
C were observed in normocholesterolemic subjects and statin-treated patients. The
primate model markedly underestimated human lipogenic responses and did not
predict human neutrophil effects. These studies demonstrate both beneficial and
adverse LXR agonist clinical responses and emphasize the importance of further
translational research in this area.
PMID- 27508872
TI - Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman
Primates, and Rodents.
AB - Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator
of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms
relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous
GALNT2 deficiency on HDL-C in humans and mammalian models. We identified two
humans homozygous for loss-of-function mutations in GALNT2 who demonstrated low
HDL-C. We also found that GALNT2 loss of function in mice, rats, and nonhuman
primates decreased HDL-C. O-glycoproteomics studies of a human GALNT2-deficient
subject validated ANGPTL3 and ApoC-III as GalNAc-T2 targets. Additional
glycoproteomics in rodents identified targets influencing HDL-C, including
phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP
activity in humans and rodents, and in mice this was rescued by reconstitution of
hepatic Galnt2. We also found that GALNT2 GWAS SNPs associated with reduced HDL-C
also correlate with lower hepatic GALNT2 expression. These results posit GALNT2
as a direct modulator of HDL metabolism across mammals.
PMID- 27508873
TI - Human and Mouse Brown Adipose Tissue Mitochondria Have Comparable UCP1 Function.
AB - Brown adipose tissue (BAT) plays an important role in mammalian thermoregulation.
The component of BAT mitochondria that permits this function is the inner
membrane carrier protein uncoupling protein 1 (UCP1). To the best of our
knowledge, no studies have directly quantified UCP1 function in human BAT.
Further, whether human and rodent BAT have comparable thermogenic function
remains unknown. We employed high-resolution respirometry to determine the
respiratory capacity, coupling control, and, most importantly, UCP1 function of
human supraclavicular BAT and rodent interscapular BAT. Human BAT was sensitive
to the purine nucleotide GDP, providing the first direct evidence that human BAT
mitochondria have thermogenically functional UCP1. Further, our data demonstrate
that human and rodent BAT have similar UCP1 function per mitochondrion. These
data indicate that human and rodent BAT are qualitatively similar in terms of
UCP1 function.
PMID- 27508874
TI - Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of
Skeletal Muscle.
AB - NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell
types. However, the availability of NAD in several tissues can become limited
during genotoxic stress and the course of natural aging. The point at which NAD
restriction imposes functional limitations on tissue physiology remains unknown.
We examined this question in murine skeletal muscle by specifically depleting
Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a
dramatic 85% decline in intramuscular NAD content, accompanied by fiber
degeneration and progressive loss of both muscle strength and treadmill
endurance. Administration of the NAD precursor nicotinamide riboside rapidly
ameliorated functional deficits and restored muscle mass despite having only a
modest effect on the intramuscular NAD pool. Additionally, lifelong
overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged
mice, supporting a critical role for tissue-autonomous NAD homeostasis in
maintaining muscle mass and function.
PMID- 27508875
TI - Colonic Pro-inflammatory Macrophages Cause Insulin Resistance in an Intestinal
Ccl2/Ccr2-Dependent Manner.
AB - High-fat diet (HFD) induces low-grade chronic inflammation and insulin
resistance. However, little is known about the mechanism underlying HFD-induced
chronic inflammation in peripheral insulin-responsive tissues. Here, we show that
colonic pro-inflammatory macrophages regulate insulin sensitivity under HFD
conditions. To investigate the pathophysiological role of colonic macrophages, we
generated macrophage-specific chemokine (C-C Motif) receptor 2 (Ccr2) knockout (M
Ccr2KO) and intestinal epithelial cell-specific tamoxifen-inducible Ccl2 knockout
(Vil-Ccl2KO) mice. Both strains exhibited similar body weight to control under
HFD. However, they exhibited decreased infiltration of colonic pro-inflammatory
macrophages, decreased intestinal permeability, and inactivation of the colonic
inflammasome. Interestingly, they showed significantly improved glucose tolerance
and insulin sensitivity with decreased chronic inflammation of adipose tissue.
Therefore, inhibition of pro-inflammatory macrophage infiltration prevents HFD
induced insulin resistance and could be a novel therapeutic approach for type 2
diabetes.
PMID- 27508876
TI - Acidosis Drives the Reprogramming of Fatty Acid Metabolism in Cancer Cells
through Changes in Mitochondrial and Histone Acetylation.
AB - Bioenergetic preferences of cancer cells foster tumor acidosis that in turn leads
to dramatic reduction in glycolysis and glucose-derived acetyl-coenzyme A (acetyl
CoA). Here, we show that the main source of this critical two-carbon intermediate
becomes fatty acid (FA) oxidation in acidic pH-adapted cancer cells. FA-derived
acetyl-CoA not only fuels the tricarboxylic acid (TCA) cycle and supports tumor
cell respiration under acidosis, but also contributes to non-enzymatic
mitochondrial protein hyperacetylation, thereby restraining complex I activity
and ROS production. Also, while oxidative metabolism of glutamine supports the
canonical TCA cycle in acidic conditions, reductive carboxylation of glutamine
derived alpha-ketoglutarate sustains FA synthesis. Concomitance of FA oxidation
and synthesis is enabled upon sirtuin-mediated histone deacetylation and
consecutive downregulation of acetyl-CoA carboxylase ACC2 making mitochondrial
fatty acyl-CoA degradation compatible with cytosolic lipogenesis. Perturbations
of these regulatory processes lead to tumor growth inhibitory effects further
identifying FA metabolism as a critical determinant of tumor cell proliferation
under acidosis.
PMID- 27508877
TI - Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese
Humans: A Randomized Double-Blind Placebo-Controlled Trial.
PMID- 27508878
TI - SnapShot: Exercise Metabolism.
AB - Exercise represents a major challenge to whole-body homeostasis. To meet this
challenge, myriad acute and adaptive responses take place at multiple cellular
and systemic levels. The molecular bases of skeletal muscle adaptations to
exercise are mediated by an array of signaling events, pre- and post
transcriptional processes, regulation of translation, and ultimately the
increased abundance and/or maximal activity of key proteins with roles in energy
provision.
PMID- 27508879
TI - Synthesis and biological activity of furoxan derivatives against Mycobacterium
tuberculosis.
AB - Tuberculosis (TB) remains a serious health problem responsible to cause millions
of deaths annually. The scenario becomes alarming when it is evaluated that the
number of new drugs does not increase proportionally to the emergence of
resistance to the current therapy. Furoxan derivatives, known as nitric oxide
(NO) donors, have been described to exhibit antitubercular activity. Herein, a
novel series of hybrid furoxan derivatives (1,2,5-oxadiazole 2-N-oxide)
(compounds 4a-c, 8a-c and 14a-c) were designed, synthesized and evaluated in
vitro against Mycobacterium tuberculosis (MTB) H37Rv (ATCC 27294) and a clinical
isolate MDR-TB strain. The furoxan derivatives have exhibited MIC90 values
ranging from 1.03 to 62 MUM (H37Rv) and 7.0-50.0 MUM (MDR-TB). For the most
active compounds (8c, 14a, 14b and 14c) the selectivity index ranged from 3.78 to
52.74 (MRC-5 cells) and 1.25-34.78 (J774A.1 cells). In addition, it was
characterized for those compounds logPo/w values between 2.1 and 2.9. All
compounds were able to release NO at levels ranging from 0.16 to 44.23%. Among
the series, the phenylsulfonyl furoxan derivatives (compounds 14a-c) were the
best NO-donor with the lowest MIC90 values. The most active compound (14c) was
also stable at different pHs (5.0 and 7.4). In conclusion, furoxan derivatives
were identified as new promising compounds useful to treat tuberculosis.
PMID- 27508880
TI - Effect of visible laser light on ATP level of anaemic red blood cell.
AB - In this work we present influence of visible laser light on ATP level and
viability of anaemic red blood cell (RBC). The visible laser lights used in this
work are 460nm and 532nm. The responses of ATP level in anaemic and normal RBC
before and after laser irradiation at different exposure time (30, 40, 50 and
60s) were observed. Three aliquots were prepared from the
ethylenediaminetetraacetic acid (EDTA) blood sample. One served as a control
(untreated) and another two were irradiated with 460nm and 560nm lasers. Packed
RBC was prepared to study ATP level in the RBC using CellTiter-GloLuminescent
cell Viability Assay kit. The assay generates a glow type signal produced by
luciferase reaction, which is proportional to the amount of ATP present in RBCs.
Paired t-test were done to analyse ATP level before and after laser irradiation.
The results revealed laser irradiation improve level of ATP in anaemic RBC.
Effect of laser light on anaemic RBCs were significant over different exposure
time for both 460nm (p=0.000) and 532nm (p=0.003). The result of ATP level is
further used as marker for RBC viability. The influence of ATP level and
viability were studied. Optical densities obtained from the data were used to
determine cell viability of the samples. Results showed that laser irradiation
increased viability of anaemic RBC compared to normal RBC.
PMID- 27508881
TI - Pigments from UV-resistant Antarctic bacteria as photosensitizers in Dye
Sensitized Solar Cells.
AB - Here we report the use of pigments produced by UV-resistant Antarctic bacteria as
photosensitizers in Dye Sensitized Solar Cells (DSSCs). Pigments were obtained
from red and yellow colored psychrotolerant bacteria isolated from soils of King
George Island, Antarctica. Based on metabolic characteristics and 16s DNA
sequence, pigmented bacteria were identified as Hymenobacter sp. (red) and
Chryseobacterium sp. (yellow). Pigments produced by these microorganisms were
extracted and classified as carotenoids based on their spectroscopic and
structural characteristics, determined by UV-Vis spectrophotometry and infrared
spectroscopy (FTIR), respectively. With the purpose of develop green solar cells
based on bacterial pigments, the photostability and capacity of these molecules
as light harvesters in DSSCs were determined. Absorbance decay assays determined
that bacterial carotenoids present high photostability. In addition, solar cells
based on these photosensitizers exhibit an open circuit voltage (VOC) of 435.0
[mV] and a short circuit current density (ISC) of 0.2 [mA.cm(-2)] for the red
pigment, and a VOC of 548.8 [mV] and a ISC of 0.13 [mA.cm(-2)] for the yellow
pigment. This work constitutes the first approximation of the use of pigments
produced by non-photosynthetic bacteria as photosensitizers in DSSCs. Determined
photochemical characteristics of bacterial pigments, summed to their easy
obtention and low costs, validates its application as photosensitizers in next
generation biological solar cells.
PMID- 27508882
TI - Toll-like receptor 9 enhances bacterial clearance and limits lung consolidation
in murine pneumonia caused by methicillin resistant Staphylococcus aureus.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in
pneumonia, associated with severe lung damage. Tissue injury causes release of
Damage Associated Molecular Patterns (DAMPs), which may perpetuate inflammation.
DNA has been implicated as a DAMP that activates inflammation through Toll-like
receptor (TLR)9. The aim of this study was to evaluate the role of TLR9 in MRSA
pneumonia. Wild-type (Wt) and TLR9 knockout (tlr9-/-) mice were infected
intranasally with MRSA USA300 (BK 11540) (5E7CFU) and euthanized at 6,24,48 or 72
hours for analyses. MRSA pneumonia was associated with profound release of cell
free host DNA in the airways, as reflected by increases in nucleosome and DNA
levels in bronchoalveolar lavage fluid (BALF), accompanied by transient detection
of pathogen DNA in MRSA-free BALF supernatants. In BALF, as compared to Wt -mice
tlr9-/- mice showed reduced TNFalpha and IL-6 levels at 6 hours and reduced
bacterial clearance at 6 and 24 hours post infection. Furthermore, tlr9-/- mice
exhibited a greater influx of neutrophils in BALF and increased lung
consolidation at 24 and 48 hours. This study demonstrates the release of host-
and pathogen-derived TLR9 ligands (DNA) into the alveolar space after infection
with MRSA via the airways and suggests that TLR9 has pro-inflammatory effects
during MRSA pneumonia associated with enhanced bacterial clearance and limitation
of lung consolidation.
PMID- 27508883
TI - The Physiological Profile of a Multiple Tour de France Winning Cyclist.
AB - INTRODUCTION: This case study reports a range of physiological characteristics in
a two-time Tour de France champion. METHODS: After body composition assessment
(dual-energy x-ray absorptiometry), two submaximal cycling step tests were
performed in ambient (20 degrees C, 40%) and hot and humid (30 degrees C, 60%
[HH]) conditions from which measures of gross efficiency (GE), lactate-power
landmarks, and heart rate responses were calculated. In addition,
thermoregulatory and sweat responses were collected throughout. VO2peak and peak
power output (PPO) were also identified after a separate ramp test to exhaustion.
RESULTS: VO2peak and PPO were 5.91 L.min (84 mL.kg.min) and 525 W, respectively,
whereas mean GE values were 23.0% and 23.6% for ambient and HH conditions,
respectively. In addition to superior GE, power output at 4 mmol.L lactate was
higher in HH versus ambient conditions (429.6 vs 419.0 W) supporting anecdotal
reports from the participant of good performance in the heat. Peak core and skin
temperature, sweat rate, and electrolyte content were higher in HH conditions.
Body fat percentage was 9.5%, whereas total fat mass, lean mass, and bone mineral
content were 6.7, 61.5, and 2.8 kg, respectively. CONCLUSION: The aerobic
physiology and PPO values indentified are among the highest reported for
professional road cyclists. Notably, the participant displayed both a high
VO2peak and GE, which is uncommon among elite cyclists and may be a contributing
factor to their success in elite cycling. In addition, performance in HH
conditions was strong, suggesting effective thermoregulatory physiology. In
summary, this is the first study to report physiological characteristics of a
multiple Tour de France champion in close to peak condition and suggests what may
be the prerequisite physiological and thermoregulatory capacities for success at
this level.
PMID- 27508884
TI - An Amperometric Immunosensor Based on an Ionic Liquid and Single-Walled Carbon
Nanotube Composite Electrode for Detection of Tetrodotoxin in Pufferfish.
AB - An amperometric immunosensor based on a composite electrode of single-walled
carbon nanotubes and ionic liquid n-octylpyridinum afluorophosphate (SWCNT-ILE)
was developed for the determination of tetrodotoxin (TTX). Compared with the
glassy carbon electrode (GCE), the electrode combined advantages of carbon
nanotubes and ionic liquid, which exhibited the excellent antifouling ability of
p-nitrophenol (PNP) so that it remarkably improved the stability of the p
nitrophenyl phosphate-based sensor. Combining the enzyme-linked immune sorbent
assay (ELISA) by alkaline phosphatase (AP) and magnetic particles immobilized
with antigens, a real-time assay of tetrodotoxin was developed by amperometric
immunosensors. Under the optimium condition, the developed sensor demonstrated a
linear range of tetrodotoxin from 2 to 45 ng/mL with a low detection limit of 5
ng/mL. Furthermore, the amperometric immunosensor was applied to determine TTX in
real samples and could be used as an effective and sensitive sensor for direct
detection of tetrodotoxin within 20 min.
PMID- 27508885
TI - [Laser-induced Maculopathy Caused by Strangers].
AB - Background: Laser-induced ocular injuries are of public interest, especially when
caused by strangers. Clinical signs and follow-up: Two laser-induced
maculopathies were presented which had been caused by strangers. Morphological
findings were shown by funduscopy and Spectralis Domain OCT follow-up.
Conclusion: Severe retina injuries can be induced by laser pointers of higher
classes.
PMID- 27508886
TI - [Methotrexate in Atypical Non-Arteritic Ischemic Optic Neuropathy].
AB - Background: Optic nerve disease can occur from a variety of different causes,
with vascular, inflammatory or toxic pathologies. In such cases, it is hardly
possible to clarify the aetiology. These diseases of the optic nerve are usually
accompanied by progressive loss of visual field and visual impairment. Patient:
We report a case of a 74-year-old woman complaining of loss of visual acuity,
visual and blurred vision in the left eye in 2010. We made the diagnosis of non
arteritic ischemic optic neuropathy (NAION). With steroid therapy, there was an
improvement in both visual acuity and visual field defects. But if an attempt was
made to reduce steroids, her condition progressed. Except for a very small optic
disk and arterial hypotension, there were no typical risk factors for NAION. We
started treatment with methotrexate (MTX), with a starting dose of 10 mg per
week, and observed the patient over two years. Results: Using MTX therapy, the
swelling of the optic nerve head and visual field loss were reversible, so we
increased the dose of MTX up to 15 mg/week. Steroid therapy could be stopped and
the patient's visual acuity and visual field have now been stable for two years.
There was no visible pallor in the optic nerve head, as normally occurs after
AION, so we considered different underlying pathologies, including autoimmune
disease. There were no adverse events with MTX therapy. Conclusion: If the course
of the disease is atypical, the pathology may include an autoimmune component.
Immunosuppressive MTX therapy may be started in order to avoid long-term steroid
use. It may then be possible to maintain a stable visual field and prevent
remitting episodes.
PMID- 27508887
TI - [Indication and Results of the Anderson Procedure].
AB - The major goal of extraocular muscle surgery for nystagmus is to reduce the
abnormal head turn (AHT) which is caused by an eccentric null zone of the
nystagmus. Shifting the null zone to the primary gaze position will eliminate the
AHT. The Kestenbaum procedure consists of bilateral recession of the yoke muscles
opposite to the AHT, combined with bilateral resection or plication of their
antagonists. The Anderson procedure is confined to bilateral recession of the
yoke muscles and is therefore less invasive. We report on our experience with the
Anderson procedure. Patients and Methods: From September 2013 to June 2015, we
performed the Anderson procedure in 11 consecutive orthotropic patients with
infantile idiopathic or sensory defect nystagmus. Patients responsive to
convergence inducing prisms who could benefit from artificial divergence surgery
were excluded. Results: Medians and ranges (minimum-maximum) were: Age 7 years (4
30); binocular BCVA 0.5 (0.05-1.0); AHT 30 degrees (20-40); equal recessions on
the horizontal yoke muscles opposite to the AHT of 12 mm (10-17), in one case
using bovine pericardium grafts. Three (3-6) months post surgery, the AHT was
reduced to 7 degrees (0-20). First step success rates, defined by residual AHT
<= 10 degrees and <= 15 degrees , were 73 % (95 % CI 39-93 %) and 82 % (95 % CI
48-97 %). No over-correction or other adverse effects were observed. Two patients
later received augmenting surgery. One patient with pre-existing exophoria later
required strabismus surgery for exotropia. Conclusion: The AHT can be
significantly reduced or completely corrected by the Anderson procedure.
Recessions of at least 10 mm on both yoke muscles were performed. The success
rates equaled success rates of augmented Kestenbaum surgery. Compared to the
latter, the Anderson procedure is less invasive. It is followed by a shorter
healing process. It is a vessel sparing method - an advantage for potential
future surgery.
PMID- 27508888
TI - [Visual Snow Syndrome: Symptoms and Ophthalmological Findings].
AB - Background The symptom "visual snow" describes the continuous perception of tiny
flickering dots within the whole visual field of both eyes. The diagnosis of a
visual snow syndrome requires the appearance of typical additional visual
symptoms and the exclusion of ophthalmological or neurological causes, or
pharmacological influences. Patients and Methods Three male and four female
subjects between 13 and 36 years of age referred with visual snow were
investigated and asked about their symptoms. A complete ophthalmological
investigation, including binocular fundoscopy, was performed in all patients.
Furthermore, best corrected visual acuity, perimetry, binocular functions, colour
vision (D15-test), full-field ERG, pattern-reversal VEP and SD-OCT images of
macula and optic nerve (RNFL) were analysed. Results Visual acuity of at least
1.0 and normal findings for all further investigations were observed in all
patients. The following additional visual symptoms were identified: illusionary
palinopsia (n = 6), disturbance of night vision (n = 5), positive light phenomena
(n = 7). A history of migraine with aura was reported in five patients. The
intake of hallucinogenic drugs or centrally active pharmaceuticals was denied by
all patients. The findings of available or initiated neurological investigations
were normal. Conclusions The visual snow syndrome has to be regarded as a
diagnosis of exclusion. Visual function parameters are not impaired. Apart from
eye diseases, a persistent migraine aura as well as neurological diseases or the
intake of hallucinogenic drugs must be excluded as possible causes of visual snow
and palinopsia.
PMID- 27508889
TI - [Comparison of the Results of the Flicker Perimetry (Prototype versus Commercial
Perimeter)].
AB - Background: Analysis of the comparison of flicker perimetry with the prototype
Pulsar and the new Octopus 600. Methods: Both eyes of 20 patients with primary
open-angle glaucoma were studied with 30 degrees visual field flimmer perimetry
(dynamic strategy) at the perimeters Pulsar and Octopus 600 (Haag-Streit). The
evaluation was based on the mean defect (MD = mean deviation) and the defect
depth (square root of lost variance = sLV). Results: In the t test for paired
samples, the Pulsar perimetry showed significantly higher values than the Octopus
600 perimetry: right eye MD 4.8 +/- 3.6 src vs. 1.7 +/- 2.9 src, p = 0.005; left
eye MD 3.9 +/- 3.6 src v. 1.4 +/- 2.8 src, p = 0.018; both eyes MD 4.35 +/- 3.62
src vs. 1.55 +/- 2.80 src, p = 0.002. The sLV values with the Pulsar perimetry
were significantly higher than the values with the Octopus 600 perimetry: right
eye sLV 3.6 +/- 1.6 vs. 2.3 +/- 1.3 src, p = 0.006; left eye sLV 3.2 +/- 0.8 vs.
2.0 +/- 0.8 src, p < 0.0001; both eyes sLV 3.37 +/- 1.28 src vs. 2.12 +/- 1.05
src, p < 0.0001. The significances even persisted after the Bonferroni-Holm
correction. Conclusion: The investigation results of flicker perimetry are not
comparable, because there is a significant difference in MD and sLV. This mainly
due to different light intensities, background brightness and varying colour
scalings of the perimetric device.
PMID- 27508890
TI - ["Eight Days After a Substantial Pleuritic Exudation" - Albrecht von Graefe to
William Bowman, the Discovery of Glaucomatous Optic Disc Cupping, and Newly
Discovered Graefe Manuscripts].
PMID- 27508891
TI - [Severe Eyeball and Facial Skeletal Injuries Caused by Firefighting Sport].
AB - The aim of this work is to draw attention to possible injuries of the eye and the
facial skeleton caused by firefighting sport. There was a group of 9 patients
presented who were treated from 2006 to 2015 in the Department of Ophthalmology
at the University Hospital in Pilsen and diagnosed with severe eyeball contusion
after being hit by a jet of water and/or a water pipe. Three cases are presented
in detail.
PMID- 27508892
TI - Visualization of NRAS RNA G-Quadruplex Structures in Cells with an Engineered
Fluorogenic Hybridization Probe.
AB - The RNA G-quadruplex is an important secondary structure formed by guanine-rich
RNA sequences. However, its folding studies have mainly been studied in vitro.
Accurate identification of RNA G-quadruplex formation within a sequence of
interest remains difficult in cells. Herein, and based on the guanine-rich
sequence in the 5'-UTR of NRAS mRNA, we designed and synthesized the first G
quadruplex-triggered fluorogenic hybridization (GTFH) probe, ISCH-nras1, for the
unique visualization of the G-quadruplexes that form in this region. ISCH-nras1
is made up of two parts: The first is a fluorescent light-up moiety specific to G
quadruplex structures, and the second is a DNA molecule that can hybridize with a
sequence that is adjacent to the guanine-rich sequence in the NRAS mRNA 5'-UTR.
Further evaluation studies indicated that ISCH-nras1 could directly and precisely
detect the targeted NRAS RNA G-quadruplex structures, both in vitro and in cells.
Thus, this GTFH probe was a useful tool for directly investigating the folding of
G-quadruplex structures within an RNA of interest and represents a new direction
for the design of smart RNA G-quadruplex probes.
PMID- 27508894
TI - Prepregnancy Body Mass Index by Maternal Characteristics and State: Data From the
Birth Certificate, 2014.
AB - Objectives-This report describes prepregnancy body mass index (BMI) among women
giving birth in 2014 for the 47-state and District of Columbia reporting areas
that implemented the 2003 U.S. Standard Certificate of Live Birth by January 1,
2014.
PMID- 27508896
TI - To Invest or Not to Invest, That Is the Question: Analysis of Firm Behavior under
Anticipated Shocks.
AB - When companies are faced with an upcoming and expected economic shock some of
them tend to react better than others. They adapt by initiating investments thus
successfully weathering the storm, while others, even though they possess the
same information set, fail to adopt the same business strategy and eventually
succumb to the crisis. We use a unique setting of the recent financial crisis in
Croatia as an exogenous shock that hit the country with a time lag, allowing the
domestic firms to adapt. We perform a survival analysis on the entire population
of 144,000 firms in Croatia during the period from 2003 to 2015, and test whether
investment prior to the anticipated shock makes firms more likely to survive the
recession. We find that small and micro firms, which decided to invest, had
between 60 and 70% higher survival rates than similar firms that chose not to
invest. This claim is supported by both non-parametric and parametric tests in
the survival analysis. From a normative perspective this finding could be
important in mitigating the negative effects on aggregate demand during strong
recessionary periods.
PMID- 27508895
TI - Highly Selective Dopamine D3 Receptor (D3R) Antagonists and Partial Agonists
Based on Eticlopride and the D3R Crystal Structure: New Leads for Opioid
Dependence Treatment.
AB - The recent and precipitous increase in opioid analgesic abuse and overdose has
inspired investigation of the dopamine D3 receptor (D3R) as a target for
therapeutic intervention. Metabolic instability or predicted toxicity has
precluded successful translation of previously reported D3R-selective antagonists
to clinical use for cocaine abuse. Herein, we report a series of novel and D3R
crystal structure-guided 4-phenylpiperazines with exceptionally high D3R
affinities and/or selectivities with varying efficacies. Lead compound 19 was
selected based on its in vitro profile: D3R Ki = 6.84 nM, 1700-fold D3R versus
D2R binding selectivity, and its metabolic stability in mouse microsomes.
Compound 19 inhibited oxycodone-induced hyperlocomotion in mice and reduced
oxycodone-induced locomotor sensitization. In addition, pretreatment with 19 also
dose-dependently inhibited the acquisition of oxycodone-induced conditioned place
preference (CPP) in rats. These findings support the D3R as a target for opioid
dependence treatment and compound 19 as a new lead molecule for development.
PMID- 27508897
TI - Insulin modulates energy and substrate sensing and protein catabolism induced by
chronic peritonitis in skeletal muscle of neonatal pigs.
AB - BACKGROUND: Acute infection promotes skeletal muscle wasting and insulin
resistance, but the effect of insulin on energy and substrate sensing in skeletal
muscle of chronically infected neonates has not been studied. METHODS: Eighteen 2
d-old pigs underwent cecal ligation and puncture (CLP) or sham surgery (CON) to
induce a chronic infection for 5 d. On d 5, pancreatic-substrate clamps were
performed to attain fasting or fed insulin levels but to maintain glucose and
amino acids in the fasting range. Total fractional protein synthesis rates (Ks),
translational control mechanisms, and energy sensing and degradation signal
activation were measured in longissimus dorsi muscle. RESULTS: In fasting
conditions, CLP reduced Ks and sirtuin 1 (SIRT1) and increased AMP-activated
protein kinase alpha (AMPKalpha) activation and muscle RING-finger protein-1
(MuRF1). Insulin treatment increased Ks and mitochondrial protein synthesis,
enhanced translation activation, and reduced SIRT1 in CON. In contrast, in CLP,
insulin treatment increased Ks, protein kinase B (PKB) and Forkhead box O1
phosphorylation, antagonized AMPK activation, and decreased peroxisome
proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha), MuRF1,
and SIRT1. CONCLUSION: Energy and substrate sensing in skeletal muscle by the PKB
AMPK-SIRT1-PGC-1alpha axis is impacted by chronic infection in neonatal pigs and
can be modulated by insulin.
PMID- 27508898
TI - New Insights from Zinc and Copper Isotopic Compositions into the Sources of
Atmospheric Particulate Matter from Two Major European Cities.
AB - This study reports spatial and temporal variability of Zn and Cu isotopes in
atmospheric particulate matter (PM) collected in two major European cities with
contrasting atmospheric pollution, Barcelona and London. We demonstrate that
nontraditional stable isotopes identify source contributions of Zn and Cu and can
play a major role in future air quality studies. In Barcelona, samples of fine PM
were collected at street level at sites with variable traffic density. The
isotopic signatures ranged between -0.13 +/- 0.09 and -0.51 +/- 0.050/00 for
delta(66)ZnIRMM and between +0.04 +/- 0.20 and +0.33 +/- 0.150/00 for
delta(65)CuAE633. Copper isotope signatures similar to those of Cu sulfides and
Cu/Sb ratios within the range typically found in brake wear suggest that
nonexhaust emissions from vehicles are dominant. Negative Zn isotopic signatures
characteristic for gaseous emissions from smelting and combustion and large
enrichments of Zn and Cd suggest contribution from metallurgical industries. In
London, samples of coarse PM collected on the top of a building over 18 months
display isotope signatures ranging between +0.03 +/- 0.04 and +0.49 +/- 0.020/00
for delta(66)ZnIRMM and between +0.37 +/- 0.17 and +0.97 +/- 0.210/00 for
delta(65)CuAE633. Heavy Cu isotope signatures (up to +0.97 +/- 0.210/00) and
higher enrichments and Cu/Sb ratios during winter time indicate important
contribution from fossil fuel combustion. The positive delta(66)ZnIRMM signatures
are in good agreement with signatures characteristic for ore concentrates used
for the production of tires and galvanized materials, suggesting nonexhaust
emissions from vehicles as the main source of Zn pollution.
PMID- 27508899
TI - Diabetes mellitus and drug abuse during pregnancy and the risk for orofacial
clefts and related abnormalities.
AB - OBJECTIVE: to assessed the prevalence of diabetes mellitus (DM) and drug abuse in
mothers of children with orofacial clefts (OFC). METHODS: 325 women who had
children (0-3y) with clefts were interviewed. Data regarding type of diabetes,
use of legal/illegal drugs during pregnancy, waist girth and fasting blood sugar
at the first prenatal consult were collected. RESULTS: twenty seven percent of
the women had DM, out of these, 89% had gestational DM, 5,5% type 1 DM and 5,5%
type 2 DM. The prevalence of DM in mothers of children with OFC was 27%, it is
significantly higher than the average Brazilian population which is 7.6% (p<0.01)
(OR=4.5, 95%CI=3.5-5.8). Regarding drug abuse during pregnancy, 32% of the
mothers used drugs and a significant positive correlation was observed between
drug abuse and the occurrence of clefts and other craniofacial anomalies
(p=0.028) (OR=2.87; 95%CI=1.1-7.4). CONCLUSIONS: DM and drug abuse during
pregnancy increases the risk for OFC and related anomalies and early diagnosis of
DM and prevention of drug abuse, especially in pregnant women, should be
emphasized.
PMID- 27508900
TI - Quality of life in the workplace for nursing staff at public healthcare
institutions.
AB - OBJECTIVE: to determine the quality of life in the workplace for nursing staff at
public institutions in Hermosillo, Sonora, Mexico. METHOD: quantitative,
correlational, cross-sectional, and comparative. We used a probabilistic sample
of 345 nurses with data collected in 2013 using an instrument created by the
authors to gather bio-socio-demographic data and the CVT-GOHISALO instrument with
a Cronbach's alpha of 0.95. SPSS 15 was used to analyze the data. A Kolmogorov
Smirnov test was used to calculate the normality of the data; the medians were
compared using the Mann-Whitney U test and Kruskal-Wallis test with the
significance level set at 0.05. RESULTS: the average overall quality of life in
the workplace for nursing staff was 207.31 (DE 41.74), indicating a moderate
level. The quality of life in the workplace was higher for people with permanent
contracts (p=0.007) who did not engage in other remunerative activities
(p=0.046). Differences in the quality of life in the workplace were observed
depending on the institution where the subjects worked (p=0.001). CONCLUSION: the
nursing staff perceives itself as having a moderate-level quality of life in the
workplace. This level was determined in the statistical analysis based on the
type of contract, whether the person performed other remunerated activities, and
the institution where the person worked.
PMID- 27508901
TI - Second-Generation central venous catheter in the prevention of bloodstream
infection: a systematic review.
AB - OBJECTIVE: to evaluate the effectiveness and safety in the use of second
generation central venous catheters impregnated in clorhexidine and silver
sulfadiazine when compared with other catheters, being them impregnated or not,
in order to prevent the bloodstream infection prevention. METHOD: systematic
review with meta-analysis. Databases searched: MEDLINE, EMBASE, CINAHL,
LILACS/SciELO, Cochrane CENTRAL; search in Congress Proceedings and records from
Clinical Trials. RESULTS: 1.235 studies were identified, 97 were pre-selected and
4 were included. In catheter-related bloodstream infection, there was no
statistical significance between second-generation impregnated catheter compared
with the non-impregnated ones, absolute relative risk 1,5% confidence interval
95% (3%-1%), relative risk 0,68 (confidence interval 95%, 0,40-1,15) and number
needed to treat 66. In the sensitivity analysis, there was less bloodstream
infection in impregnated catheters (relative risk 0,50, confidence interval 95%,
0,26-0,96). Lower colonization, absolute relative risk 9,6% (confidence interval
95%, 10% to 4%), relative risk 0,51 (confidence interval 95% from 0,38-0,85) and
number needed to treat 5. CONCLUSION: the use of second-generation catheters was
effective in reducing the catheter colonization and infection when a sensitivity
analysis is performed. Future clinical trials are suggested to evaluate sepsis
rates, mortality and adverse effects. OBJETIVO: evaluar la efectividad y
seguridad del uso de cateteres venosos centrales de segunda generacion,
impregnados en clorhexidina y sulfadiazina de plata, comparados con otros
cateteres impregnados o no impregnados, para prevencion de infeccion de la
corriente sanguinea. METODO: revision sistematica con metaanalisis. La busqueda
fue realizada en las bases: MEDLINE, EMBASE, CINAHL, LILACS/SciELO, Cochrane
CENTRAL; fueron consultados anales de congresos y registros de ensayos clinicos.
RESULTADOS: fueron identificados 1.235 estudios, 97 preseleccionados y cuatro
incluidos. En la infeccion de la corriente sanguinea, relacionada al cateter, no
hubo significacion estadistica entre cateter de segunda generacion impregnado en
comparacion a los no impregnados, riesgo relativo absoluto 1,5%, intervalo de
confianza 95% (3%-1%), riesgo relativo 0,68 (intervalo de confianza 95%, 0,40
1,15) y numero necesario para tratar 66. En el analisis de sensibilidad, hubo
disminucion de la infeccion de la corriente sanguinea en los cateteres
impregnados (riesgo relativo 0,50, intervalo de confianza 95%, 0,26-0,96).
Reduccion de la colonizacion, riesgo relativo absoluto de 9,6% (intervalo de
confianza 95%, 10% a 4%), riesgo relativo 0,51 (intervalo de confianza 95% de
0,38-0,85) y numero necesario para tratar 5. CONCLUSION: el uso de los cateteres
de segunda generacion fue efectivo en la reduccion de la colonizacion del cateter
y de infeccion cuando realizado analisis de sensibilidad. Se sugirieron ensayos
clinicos futuros que evaluen tasas de sepsis, mortalidad y efectos adversos.
OBJETIVO: avaliar a efetividade e seguranca do uso de cateteres venosos centrais
de segunda geracao, impregnados em clorexidina e sulfadiazina de prata,
comparados com outros cateteres impregnados ou nao, na prevencao de infeccao de
corrente sanguinea. METODO: revisao sistematica com metanalise. Busca realizada
nas bases: MEDLINE, EMBASE, CINAHL, LILACS/SciELO, Cochrane CENTRAL; consulta em
anais de congresso e registro de ensaios clinicos. RESULTADOS: foram
identificados 1.235 estudos, 97 pre-selecionados e quatro incluidos. Na infeccao
de corrente sanguinea, relacionada ao cateter, nao houve significancia
estatistica entre cateter de segunda geracao impregnado em comparacao aos nao
impregnados risco relativo absoluto 1,5%, intervalo de confianca 95% (3%-1%),
risco relativo 0,68 (intervalo de confianca 95%, 0,40-1,15) e numero necessario
para tratar 66. Na analise de sensibilidade, houve diminuicao da infeccao de
corrente sanguinea nos cateteres impregnados (risco relativo 0,50, intervalo de
confianca 95%, 0,26-0,96). Reducao da colonizacao, risco relativo absoluto de
9,6% (intervalo de confianca 95%, 10% a 4%), risco relativo 0,51 (intervalo de
confianca 95% de 0,38-0,85) e numero necessario para tratar 5. CONCLUSAO: o uso
dos cateteres de segunda geracao foi efetivo na reducao de colonizacao do cateter
e de infeccao quando realizada analise de sensibilidade. Sugerem-se ensaios
clinicos futuros que avaliem taxas de sepse, mortalidade e efeitos adversos.
PMID- 27508902
TI - Care management: agreement between nursing prescriptions and patients' care
needs.
AB - OBJECTIVES: analyze agreement between nursing prescriptions recorded in medical
files and patients' care needs; investigate the correlation between the nurses'
professional background and agreement of prescriptions. METHOD: descriptive study
with quantitative and documentary approach conducted in the medical clinic,
surgical, and specialized units of a university hospital in the interior of Sao
Paulo, Brazil. The new validated version of a Patient Classification Instrument
was used and 380 nursing prescriptions written at the times of hospital admission
and discharge were assessed. RESULTS: 75% of the nursing prescriptions items were
compatible with the patients' care needs. Only low correlation between nursing
prescription agreement and professional background was found. CONCLUSION: the
nursing prescriptions did not fully meet the care needs of patients. The care
context and work process should be analyzed to enable more effective
prescriptions, while strategies to assess the care needs of patients are
recommended. OBJETIVOS: analisar a concordancia entre prescricoes de enfermagem,
registradas nos prontuarios, e as necessidades de cuidados dos pacientes;
investigar a correlacao entre o perfil profissional dos enfermeiros e a
concordancia das prescricoes. METODO: estudo descritivo com abordagem
quantitativa e documental, realizado em unidades de clinica medica, cirurgica e
especializada de um hospital de ensino, no interior do Estado de Sao Paulo. Foi
aplicada a nova versao validada do Instrumento de Classificacao de Pacientes e,
posteriormente, investigadas 380 prescricoes de enfermagem no momento da admissao
e alta hospitalar. RESULTADOS: foi identificado que 75% dos itens das prescricoes
de enfermagem estavam compativeis com as necessidades cuidativas dos pacientes.
Encontrou-se baixa correlacao entre a concordancia da prescricao de enfermagem e
o perfil profissional. CONCLUSAO: as prescricoes de enfermagem nao estao sendo
realizadas, em sua totalidade, em consonancia com as necessidades dos pacientes.
Para possibilitar prescricoes mais efetivas, recomenda-se analise do contexto
assistencial e processo de trabalho e o uso de estrategias avaliativas das
necessida!des de cuidados dos pacientes. OBJETIVOS: analizar la concordancia
entre prescripciones de enfermeria, registradas en las fichas medicas, y las
necesidades de cuidados de los pacientes; investigar la correlacion entre el
perfil profesional de los enfermeros y la concordancia de las prescripciones.
METODO: estudio descriptivo con abordaje cuantitativo y documental, realizado en
unidades de clinica medica, quirurgica y especializada de un hospital de
ensenanza, en el interior del Estado de Sao Paulo. Fue aplicada la nueva version
validada del Instrumento de Clasificacion de Pacientes y, posteriormente,
investigadas 380 prescripciones de enfermeria en el momento de la admision y alta
hospitalaria. RESULTADOS: fue identificado que 75% de los items de las
prescripciones de enfermeria eran compatibles con las necesidades de cuidados de
los pacientes. Se encontro baja correlacion entre la concordancia de la
prescripcion de enfermeria y el perfil profesional. CONCLUSION: las
prescripciones de enfermeria no estan siendo realizadas, en su totalidad, en
consonancia con las necesidades de los pacientes. Para posibilitar prescripciones
mas efectivas, se recomienda analizar el contexto asistencial y el proceso de
trabajo y el uso de estrategias de evaluacion de las necesidades de cuidados de
los pacientes.
PMID- 27508903
TI - Nursing interventions for rehabilitation in Parkinson's disease: cross mapping of
terms.
AB - OBJECTIVE: to perform a cross-term mapping of nursing language in the patient
record with the Nursing Interventions Classification system, in rehabilitation
patients with Parkinson's disease. METHOD: a documentary research study to
perform cross mapping. A probabilistic, simple random sample composed of 67
records of patients with Parkinson's disease who participated in a rehabilitation
program, between March of 2009 and April of 2013. The research was conducted in
three stages, in which the nursing terms were mapped to natural language and
crossed with the Nursing Interventions Classification. RESULTS: a total of 1,077
standard interventions that, after crossing with the taxonomy and refinement
performed by the experts, resulted in 32 interventions equivalent to the Nursing
Interventions Classification (NIC) system. The NICs, "Education: The process of
the disease.", "Contract with the patient", and "Facilitation of Learning" were
present in 100% of the records. For these interventions, 40 activities were
described, representing 13 activities by intervention. CONCLUSION: the cross
mapping allowed for the identification of corresponding terms with the nursing
interventions used every day in rehabilitation nursing, and compared them to the
Nursing Interventions Classification.
PMID- 27508904
TI - Diagnosis and medical treatment of neuropathic pain in leprosy.
AB - OBJECTIVE: to identify the difficulties in diagnosing and treating neuropathic
pain caused by leprosy and to understand the main characteristics of this
situation. METHODS: 85 patients were treated in outpatient units with reference
to leprosy and the accompanying pain. We used a questionnaire known as the
Douleur Neuropathic 4 test and we conducted detailed neurological exams. As a
result, 42 patients were excluded from the study for not having proved their
pain. RESULTS: Out of the 37 patients that experienced pain, 22 (59.5%) had
neuropathic pain (or a mixture of this pain and their existing pain) and of these
90.8% considered this pain to be moderate or severe. 81.8% of the sample suffered
with this pain for more than 6 months. Only 12 (54.5%) of the patients had been
diagnosed with neuropathic pain and in almost half of these cases, this pain had
not been diagnosed. With reference to medical treatment (n=12) for neuropathic
pain, 5 (41.6%) responded that they became better. For the other 7 (58.4%) there
were no changes in relation to the pain or in some cases the pain worsened in
comparison to their previous state. Statistical analysis comparing improvements
in relation to the pain amongst the patients that were treated (n=12) and those
that were not, showed significant differences (value p=0.020). CONCLUSION: we
noted difficulties in diagnosing neuropathic pain for leprosy in that almost half
of the patients that were studied had not had their pain diagnosed. We attributed
this to some factors such as the non-adoption of the appropriate protocols which
led to inadequate diagnosis and treatment that overlooked the true picture.
PMID- 27508905
TI - Building sustainability indicators in the health dimension for solid waste
management.
AB - OBJECTIVE: to prepare a list of sustainability indicators in the health
dimension, for urban solid waste management. METHODS: a descriptive and
exploratory study performed jointly with 52 solid waste specialists, using a
three-steps Delphi technique, and a scale measuring the degree of importance for
agreement among the researchers in this area. RESULTS: the subjects under study
were 92,3% PhD's concentrated in the age group from 30 to 40 years old (32,7%)
and 51% were men. At the end of the 3rd step of the Delphi process, the average
and standard deviation of all the proposed indicators varied from 4,22 (+/-0,79)
to 4,72 (+/-0,64), in a scale of scores for each indicator from 1 to 5 (from
"dispensable" to "very important"). Results showed the level of correspondence
among the participants ranging from 82% to 94% related to those indicators.
CONCLUSION: the proposed indicators may be helpful not only for the
identification of data that is updated in this area, but also to enlarge the
field of debates of the environmental health policies, directed not only for
urban solid waste but for the achievement of better health conditions for the
Brazilian context. OBJETIVO: elaborar uma lista de indicadores de
sustentabilidade na dimensao da saude para gestao de residuos solidos urbanos.
METODO: estudo descritivo e exploratorio, realizado com 52 especialistas na area
de residuos solidos, utilizando a tecnica Delphi em tres etapas, com o uso da
escala de mensuracao do grau de importancia para obtencao de consenso entre
pesquisadores da area da investigacao. RESULTADOS: dos sujeitos estudados , 92,3%
eram doutores, com maior concentracao na faixa etaria entre 30 e 40 anos (32,7%)
e 51,0% do sexo masculino. Ao final da 3a etapa de aplicacao da tecnica Delphi, a
media e o desvio-padrao de todos os indicadores propostos variaram de 4,22 (+/
0,79) a 4,72 (+/-0,64), em uma escala de pontuacao atribuida para cada indicador
de 1 a 5 (Respectivamente, de "dispensavel" a "muito importante"). Os resultados
demonstraram nivel de concordancia entre os sujeitos participantes que variou de
82% a 94% em relacao a esses indicadores. CONCLUSAO: os indicadores propostos
podem auxiliar, tanto na identificacao de dados atualizados no setor, quanto na
ampliacao das discussoes das politicas de saude ambiental, voltadas nao apenas
para residuos solidos urbanos, mas objetivando tambem o alcance de melhores
condicoes de saude no contexto da atual realidade brasileira. OBJETIVO: elaborar
una lista de indicadores de sostenibilidad en la dimension salud para la gestion
de residuos solidos urbanos. METODO: estudio descriptivo y exploratorio realizado
con 52 especialistas en el area de residuos solidos, utilizando la tecnica Delphi
en tres etapas, con uso de escala de medida de grado de importancia para
obtencion de consenso entre investigadores de esta area. RESULTADOS: de los
sujetos estudiados , 92,3% tenian doctorado con mayor concentracion en el grupo
etario entre 30 y 40 anos (32,7%) y 51% del sexo masculino. Al final de la 3a.
Etapa de aplicacion de la tecnica Delphi, el promedio y el desvio estandar de
todos los indicadores propuestos variaron de 4,22 (+/-0,79) a 4,72 (+/-0,64), en
una escala de puntos atribuida a cada indicador de 1 a 5 (Respectivamente de
"dispensable" a "muy importante"). Los resultados mostraron un nivel de acuerdo
entre los sujetos participantes que vario de 82% a 94% en relacion a estos
indicadores. CONCLUSION: los indicadores propuestos pueden ayudar tanto en la
identificacion de datos actualizados en este sector, como tambien para ampliar
las discusiones de las politicas de salud ambiental, dirigidas no solamente para
residuos solidos urbanos pero tambien para alcanzar mejores condiciones de salud
en el contexto de la realidad brasilena actual.
PMID- 27508906
TI - Lean thinking in health and nursing: an integrative literature review.
AB - OBJECTIVES: to demonstrate the scientific knowledge developed on lean thinking in
health, highlighting the impact and contributions in health care and nursing.
METHOD: an integrative literature review in the PubMed, CINAHL, Scopus, Web of
Science, Emerald, LILACS and SciELO electronic library databases, from 2006 to
2014, with syntax keywords for each data base, in which 47 articles were selected
for analysis. RESULTS: the categories were developed from the quality triad
proposed by Donabedian: structure, process and outcome. Lean thinking is on the
rise in health surveys, particularly internationally, especially in the USA and
UK, improving the structure, process and outcome of care and management actions.
However, it is an emerging theme in nursing. CONCLUSION: this study showed that
the use of lean thinking in the context of health has a transforming effect on
care and organizational aspects, promoting advantages in terms of quality, safety
and efficiency of health care and nursing focused on the patient.
PMID- 27508907
TI - Family violence against children and adolescents in context: How the territories
of care are imbricated in the picture.
AB - OBJECTIVE: to understand the context of care addressed to the families involved
in family violence against children and adolescents (IVCA), as produced in the
context of the Primary Health Care (PHC), from the vantage point of the
practitioners of a municipality in the State of Sao Paulo. METHODS: qualitative
research of the social-strategic type, based on the Complexity Paradigm. The
participants were 41 health practitioners in five health units of the
municipality under study, pertaining to the five districts of the municipality.
Data collection was done through 5 focus groups and 10 semi-structured interviews
from April 24th 2013 to December 12th 2013. Data analysis was oriented by the
comprehension and contextualization mindset and based on the dialogic, recursive
and hologramatic principles. RESULTS: two main issues regarding the care provided
by the Health of the Family team were identified: the context of this violence
(the domestic space) and the power relations that prevail in the territory where
this violence surfaces. The community health workers are the targets of specific
attention because they experience the live/work dialogic in this same area.
CONCLUSION: paying attention to the territory, and considering the complexity of
contexts and dimensions is inherently linked to the design of care to families
involved in IVCA in the PHC environment.
PMID- 27508908
TI - Prevalence of hypoalbuminemia and nutritional issues in hospitalized elders.
AB - OBJECTIVE: to estimate the prevalence of hypoalbuminemia in hospitalized elders,
related to socio-demographic variables, nutritional status and length of stay.
METHODS: crosscutting study with 200 patients hospitalized in a large hospital in
the South of Brazil during three months. Evaluations, lab tests and interviews
through questionnaires were performed. RESULTS: the average albuminemia was 2,9
+/- 0,5g/dL. Hypoalbuminemia was diagnosed in 173 subjects (87%) and was absent
in 27 (13%) that have normal albuminemia (p=0,000). After six days of
hospitalization, the prevalence of low levels grew significantly to 90%
(p=0,002), average 2,7 +/- 0,5g/dL. Using the Mini Nutritional Assessment, it was
observed that 41 patients were malnourished and from those, 40 had
hypoalbuminemia. CONCLUSION: the prevalence of hypoalbuminemia proved to be high,
in approx. nine in ten elders, and the nutritional status and the length of stay
proved to be related to the decrease of serum albumin levels. Thus, it is
suggested that monitoring albumin levels should be done to evaluate the risk that
the patient has to develop malnutrition and other complications during hospital
stays. OBJETIVO: estimar a prevalencia de hipoalbuminemia em idosos
hospitalizados, em relacao as variaveis sociodemograficas, estado nutricional e
tempo de internacao. METODO: estudo transversal, com 200 pacientes internados em
hospital de grande porte do sul do Brasil, durante o periodo de tres meses. Foram
realizadas avaliacoes, analise de exames laboratoriais e entrevista atraves de
questionario. RESULTADOS: a media de albuminemia foi 2,9 +/- 0,5g/dL. O
diagnostico de hipoalbuminemia, foi encontrado em 173 sujeitos (87%), e nao
revelado em 27 (13%), que apresentaram albuminemia normal (p=0,000). Constatou-se
que apos seis dias de internacao a prevalencia de niveis baixos aumentou
significativamente para 90% (p=0,002), com media de 2,7 +/- 0,5g/dL. Utilizando
se a Mini Avaliacao Nutricional, observou-se que 41 pacientes estavam
desnutridos, e que destes, 40 apresentavam hipoalbuminemia. CONCLUSAO: a
prevalencia de hipoalbuminemia mostrou-se elevada, acometendo aproximadamente
nove entre dez idosos, sendo que o estado nutricional, da mesma maneira que o
tempo de internacao , esta relacionado a diminuicao dos niveis de albumina
serica. Assim, sugere-se monitorar os niveis de albuminemia para avaliar o risco
que o paciente tem de desenvolver desnutricao e demais complicacoes durante a
internacao hospitalar. OBJETIVO: estimar la prevalencia de hipoalbuminemia en
ancianos hospitalizados, considerando las variables sociodemograficas, estado
nutricional y tiempo de internacion. METODO: estudio transversal, en 200
pacientes internados en hospital de gran porte del sur de Brasil, durante un
periodo de tres meses. Fueron realizadas evaluaciones, analisis de examenes de
laboratorio y se realizo una entrevista usando un cuestionario. RESULTADOS: el
promedio de albuminemia fue 2,9 +/- 0,5g/dL. El diagnostico de hipoalbuminemia,
fue encontrado en 173 sujetos (87%), y no revelado en 27 (13%), que presentaron
albuminemia normal (p=0,000). Se constato que despues de seis dias de internacion
la prevalencia de niveles bajos aumento significativamente para 90% (p=0,002),
con promedio de 2,7 +/- 0,5g/dL. Utilizando la Mini Evaluacion Nutricional, se
observo que 41 pacientes estaban desnutridos, y que de estos, 40 presentaban
hipoalbuminemia. CONCLUSION: la prevalencia de hipoalbuminemia se mostro elevada,
afectando aproximadamente nueve entre diez ancianos, siendo que el estado
nutricional, de la misma manera que el tiempo de internacion, esta relacionado a
la disminucion de los niveles de albumina serica. Asi, se sugiere monitorizar los
niveles de albuminemia para evaluar el riesgo que el paciente tiene de
desarrollar desnutricion y demas complicaciones durante la internacion
hospitalaria.
PMID- 27508909
TI - Living arrangements of the elderly and the sociodemographic and health
determinants: a longitudinal study.
AB - OBJECTIVES: to describe the sociodemographic characteristics and the number of
morbidities in the elderly, according to the dynamics of living arrangements and
evaluate the sociodemographic and health determinants of the living arrangements.
METHODS: this is a household longitudinal survey (2005-2012), carried out with
623 elderly people. Descriptive statistical analysis and multinomial logistic
regression were performed (p<0.05). RESULTS: there was predominance of elderly
living alone, accompanied and with change in the living arrangements, females,
age range between 60? 70 years, 1? 4 years of study and with income between 1?? 3
minimum wages. During the development of this research, it was identified an
increase in the incidence of elderly with 1??3 minimum wages. The number of
morbidities increased in the three groups throughout the study, with the highest
rates observed among the elderly with change in the dynamics of living
arrangements. It was found that elderly men showed less chance of living alone
(p=0.007) and having change in the living arrangements compared to women (p =
0.005). Incomes less than a minimum wage decreased the chances of change in the
living arrangements compared to incomes above three salaries (p=0.034).
CONCLUSION: the determining factors of the living arrangements were sex and
income, and the variables functional capacity and number of morbidities were not
associated with the outcome analyzed. OBJETIVOS: descrever as caracteristicas
sociodemograficas e o numero de morbidades de idosos, segundo a dinamica do
arranjo domiciliar; e verificar os determinantes sociodemograficos e de saude do
arranjo domiciliar. METODOS: trata-se de uma pesquisa domiciliar e longitudinal
(2005-2012), conduzida com 623 idosos. Foi realizada analise estatistica
descritiva e regressao logistica multinomial (p<0,05). RESULTADOS: predominaram,
idosos que moram sozinhos, acompanhados e com mudanca do arranjo domiciliar, do
sexo feminino, faixa etaria 60? 70 anos, 1? 4 anos de estudo e com renda entre
1?? 3 salarios minimos. Durante o desenvolvimento dessa pesquisa, identificou-se
uma elevacao da distribuicao de idosos com 1??3 salarios minimos. O numero de
morbidades aumentou nos tres grupos ao longo do estudo, com maiores taxas entre
os idosos que mudaram a dinamica do arranjo domiciliar. Verificou-se que idosos
do sexo masculino apresentaram menores chances de morar sozinhos (p=0,007) e
mudar o arranjo domiciliar comparados as mulheres (p = 0,005). Ganhar menos de um
salario minimo diminuiu as chances de mudanca do arranjo domiciliar em relacao
aos que ganham mais de tres salarios (p=0,034). CONCLUSAO: os fatores
determinantes do arranjo domiciliar foram o sexo e a renda, sendo que as
variaveis capacidade funcional e numero de morbidades nao estiveram associadas ao
desfecho analisado. OBJETIVOS: describir las caracteristicas sociodemograficas y
el numero de enfermedades concomitantes de ancianos, segun la dinamica de la
acomodacion domiciliaria; y verificar los determinantes sociodemograficos y de
salud del espacio domiciliario. METODOS: se trata de una investigacion
domiciliaria y longitudinal (2005-2012), realiza con 623 ancianos. Fue realizado
analisis estadistico descriptivo y regresion logistica multinomial (p<0,05).
RESULTADOS: predominaron, ancianos que viven solos, acompanados y con cambio de
acomodacion domiciliaria, del sexo femenino, intervalo etario 60? 70 anos, 1? 4
anos de estudio y con ingreso mensual entre 1??3 sueldos minimos. Durante el
desarrollo de la investigacion, se identifico una aumento en la distribucion de
ancianos de 1??3 sueldos minimos. El numero de enfermedades concomitantes aumento
en los tres grupos a lo largo del estudio, con mayores tasas entre los ancianos
que cambiaron la dinamica de la acomodacion domiciliaria. Se verifico que
ancianos del sexo masculino presentaron menores probabilidades de vivir solos
(p=0,007) y de cambiar la acomodacion domiciliaria, comparados a las mujeres (p =
0,005). Ganar menos de un salario minimo disminuye las probabilidades de cambiar
la acomodacion domiciliaria en relacion a los que ganan mas de tres sueldos
(p=0,034). CONCLUSION: los factores determinantes de la acomodacion domiciliaria
fueron el sexo y la ingreso mensual, siendo que las variables capacidad funcional
y numero de enfermedades concomitantes, no estuvieron asociadas al resultado
analizado.
PMID- 27508910
TI - The effects of acupressure on labor pains during child birth: randomized clinical
trial.
AB - OBJECTIVE: to analyze the effects of acupressure on the sanyinjiao point for
pregnant women in labor at public maternity wards. METHOD: single-blind
controlled clinical trial, randomly done employing a pragmatic profile. We
selected 156 pregnant women in their >= 37 week/s, who had cervical dilations of
>= 4 cm and with two or more contractions in 10 minutes. The pregnant women were
randomly divided into three groups at a university hospital in the suburbs of Sao
Paulo, Brazil, in order to receive either acupressure treatment, a placebo or
participate as part of a control group. The acupressure was applied on the
sanyinjiao point during the contractions for 20 minutes. Then the intensity of
the pain was evaluated using the Visual Analogue Scale (VAS). RESULTS: The
averages for the pain measured using the VAS were not different for the three
groups that were a part of the study (p-value=0.0929), however they were less in
the acupressure groups immediately after receiving the treatment (p
value=<0.0001). This was also the case where the treatment lasted for 1 hour (p
value=0.0001). This was the case in comparison with placebo and control groups.
CONCLUSION: the use of acupressure on the sanyinjiao point is a useful way to
alleviate pain in a non-invasive manner. It can improve the quality of care given
to pregnant women in labor. Register: RBR-9mhs8r.
PMID- 27508911
TI - Translation, adaptation and validation the contents of the Diabetes Medical
Management Plan for the Brazilian context.
AB - OBJECTIVE: to translate, adapt and validate the contents of the Diabetes Medical
Management Plan for the Brazilian context. This protocol was developed by the
American Diabetes Association and guides the procedure of educators for the care
of children and adolescents with diabetes in schools. METHOD: this methodological
study was conducted in four stages: initial translation, synthesis of initial
translation, back translation and content validation by an expert committee,
composed of 94 specialists (29 applied linguists and 65 health professionals),
for evaluation of the translated version through an online questionnaire. The
concordance level of the judges was calculated based on the Content Validity
Index. Data were exported into the R program for statistical analysis. RESULTS:
the evaluation of the instrument showed good concordance between the judges of
the Health and Applied Linguistics areas, with a mean content validity index of
0.9 and 0.89, respectively, and slight variability of the index between groups
(difference of less than 0.01). The items in the translated version, evaluated as
unsatisfactory by the judges, were reformulated based on the considerations of
the professionals of each group. CONCLUSION: a Brazilian version of Diabetes
Medical Management Plan was constructed, called the Plano de Manejo do Diabetes
na Escola.
PMID- 27508912
TI - Newborns' temperature submitted to radiant heat and to the Top Maternal device at
birth.
AB - OBJECTIVE: to compare the axillar temperatures of newborns that are put
immediately after birth in skin-to-skin contact under the Top Maternal device, as
compared to those in a radiant heat crib. METHODS: comparatives observational
study of the case-control type about temperature of 60 babies born at the
Obstetric Center and Normal Delivery Center of a public hospital of the
municipality of Sao Paulo, being them: 29 receiving assistance in heated crib and
31 in skin-to skin contact, shielded by a cotton tissue placed on mother's
thorax, called Top Maternal. RESULTS: the temperature of the babies of the skin
to-skin contact group presented higher values in a larger share of the time
measures verified, as compared to those that were placed in radiant heat crib,
independently from the place of birth. Differences between the two groups were
not statistically significant. CONCLUSION: the study contributes to generate new
knowledge, supporting the idea of keeping babies with their mothers immediately
after birth protected with the Maternal Top, without harming their wellbeing, as
it keeps the axillar temperature in recommendable levels.
PMID- 27508913
TI - Risk factors for medication errors in the electronic and manual prescription.
AB - OBJECTIVE: to compare electronic and manual prescriptions of a public hospital of
Brasilia, identifying risk factors for the occurrence of medication errors.
METHOD: descriptive-exploratory, comparative and retrospective study. Data
collection occurred from July 2012 to January 2013, using an instrument for the
review of the information contained in medical records related to the medication
process. A total of 190 manual and 199 electronic records composed the sample,
with 2027 prescriptions each. RESULTS: compared to the manual prescription, a
significant reduction was observed in the risk factors after implantation of the
electronic prescription, in items such as "lack of the form of dilution" (71.1%
to 22.3%) and "prescription with brand name" (99.5% to 31.5%). Conversely, the
risk factors "no check" and "lack of CRM of the prescriber" increased. The lack
of the allergy registration and the occurrences related to medication were the
same for both groups. CONCLUSION: generally, the use of the electronic
prescription system was associated with a significant reduction in risk factors
for medication errors, concerning the following aspects: illegibility,
prescription with brand name and presence of essential items that provide a safe
and effective prescription.
PMID- 27508914
TI - The effects of work on the health of nurses who work in clinical surgery
departments at university hospitals.
AB - OBJECTIVE: to analyze the effects of work on the health of nurses who work in
clinical surgery departments at university hospitals in relation to physical,
social and psychological suffering and pain. METHODS: a quantitative transversal
study was carried out between 2012 and 2013 in four institutions in a state
located in the south of Brazil. We studied 65 nurses who responded to questions
on their habits. We also obtained sociodemographical information on them as well
as conducting an evaluation on work relational damage using an evaluation scale.
Associations were checked through the use of the Chi-Sqaure and Fisher's exact
test. Correlations were checked using the Spearmann test. RESULTS: we found that
physical ailments persisted and that there were connections between social and
psychological pain/suffering and variable physical activities as well as
connections with accidents in the work place and the option to work shifts. We
noted correlations between social and psychological pain/suffering. CONCLUSION:
nurses had their health compromised due to their work in clinical surgery
departments.
PMID- 27508915
TI - Methodological proposal for validation of the disinfecting efficacy of an
automated flexible endoscope reprocessor.
AB - OBJECTIVE: to elaborate and apply a method to assess the efficacy of automated
flexible endoscope reprocessors at a time when there is not an official method or
trained laboratories to comply with the requirements described in specific
standards for this type of health product in Brazil. METHOD: the present
methodological study was developed based on the following theoretical references:
International Organization for Standardization (ISO) standard ISO 15883-4/2008
and Brazilian Health Surveillance Agency (Agencia Nacional de Vigilancia
Sanitaria - ANVISA) Collegiate Board Resolution (Resolucao de Diretoria Colegiada
- RDC) no. 35/2010 and 15/2012. The proposed method was applied to a commercially
available device using a high-level 0.2% peracetic acid-based disinfectant.
RESULTS: the proposed method of assessment was found to be robust when the
recommendations made in the relevant legislation were incorporated with some
adjustments to ensure their feasibility. Application of the proposed method
provided evidence of the efficacy of the tested equipment for the high-level
disinfection of endoscopes. CONCLUSION: the proposed method may serve as a
reference for the assessment of flexible endoscope reprocessors, thereby
providing solid ground for the purchase of this category of health products.
OBJETIVO: propor e aplicar um metodo para a avaliacao da eficacia de
processadoras automaticas de endoscopios flexiveis, em um momento em que ainda
nao existe no Brasil um metodo oficial, nem tampouco laboratorios capacitados que
contemplem os requisitos das normas especificas aplicaveis a esse tipo de produto
para a saude. METODO: caracterizou-se como pesquisa metodologica e foi
desenvolvido com base em tres referenciais teoricos: norma tecnica International
Organization for Standardization (ISO) - ISO 15883-4/2008, Resolucao de Diretoria
Colegiada (RDC) no35/2010 e RDC no15/2012 da Agencia Nacional de Vigilancia
Sanitaria (ANVISA). Aplicou-se o metodo proposto em um equipamento especifico,
comercialmente disponivel, utilizando desinfetante de alto nivel a base de acido
peracetico 0,2%. RESULTADOS: o metodo de avaliacao proposto mostrou-se robusto, a
medida que as recomendacoes das legislacoes pertinentes ao equipamento avaliado
foram incorporadas, com algumas adaptacoes para sua exequibilidade. A aplicacao
do metodo proposto permitiu atestar a eficacia do equipamento utilizado na
desinfeccao de alto nivel de endoscopios. CONCLUSAO: o metodo pode servir de
referencia para a avaliacao de reprocessadoras de endoscopios flexiveis,
subsidiando a aquisicao dessa categoria de produtos para a saude. OBJETIVO:
elaborar y aplicar un metodo para evaluar la eficacia de reprocesadores
automatizados de endoscopios flexibles en un momento en el que no hay un metodo
oficial o laboratorios capacitados para cumplir con los requisitos descritos en
las normas especificas para este tipo de producto para la salud en Brasil.
METODO: el presente estudio metodologico fue desarrollado en base a las
siguientes referencias teoricas: Organizacion Internacional de Normalizacion
(International Organization for Standardization - ISO) norma ISO 15883-4/2008 y
Agencia Nacional de Vigilancia de la Salud de Brasil (Agencia Nacional de
Vigilancia Sanitaria - ANVISA) Resolucion del Directorio Colegiado (Resolucao de
Diretoria Colegiada - RDC) No 35/2010 y 15/2012. El metodo propuesto se aplico a
un dispositivo comercialmente disponible usando un desinfectante al 0,2% a base
de acido peracetico de alto nivel. RESULTADOS: el metodo de evaluacion propuesto
se evaluo como fuerte despues de que las recomendaciones formuladas en la
legislacion pertinente se incorporaron con algunos ajustes para garantizar su
factibilidad. La aplicacion del metodo propuesto proporciona evidencia de la
eficacia de los equipos de prueba para la desinfeccion de alto nivel de
endoscopios. CONCLUSION: el metodo propuesto puede servir de referencia para la
evaluacion de reprocesadores de endoscopios flexibles, proporcionando de este
modo bases solidas para la compra de esta categoria de productos de salud.
PMID- 27508916
TI - Incidence of phlebitis associated with the use of peripheral IV catheter and
following catheter removal.
AB - OBJECTIVE: to investigate the incidence of phlebitis and its association with
risk factors when using peripheral IV catheters (PIC) and following their removal
- (post-infusion phlebitis) in hospitalized adults. METHOD: a cohort study of 171
patients using PIC, totaling 361 punctures. Sociodemographic variables and
variables associated with the catheter were collected. Descriptive and analytical
statistical analyses were performed. RESULTS: average patient age was 56.96 and
51.5% of the sample population was male. The incidence of phlebitis was 1.25%
while using PIC, and 1.38% post-infusion. The incidence of phlebitis while using
PIC was associated with the length of time the catheter remained in place,
whereas post-infusion phlebitis was associated with puncture in the forearm.
Ceftriaxone, Clarithromycin and Oxacillin are associated with post-infusion
phlebitis. CONCLUSIONS: this study made it possible to investigate the
association between risk factors and phlebitis during catheter use and following
its removal. The frequency of post-infusion phlebitis was larger than the
incidence of phlebitis with the catheter in place, with Phlebitis Grade III and
II being the most frequently found in each of these situations, respectively.
Aspects related to post-infusion phlebitis can be explained, given the limited
number of studies addressing this theme from this perspective. OBJETIVO:
investigar a incidencia de flebites e a associacao de fatores de risco com a sua
ocorrencia durante o uso e apos a retirada do cateter intravenoso periferico -
CIP (Flebite pos-infusao) em adultos hospitalizados. METODO: estudo de coorte com
171 pacientes com CIP, totalizando 361 puncoes. Foram coletadas variaveis
sociodemograficas e relacionadas ao cateter. Analise estatistica descritiva e
analitica. RESULTADOS: dos pacientes, 51,5% eram homens e a media de idade foi de
56,96 anos. A incidencia de flebites durante o uso do CIP foi de 1,25% e a pos
infusao foi de 1,38%. Associou-se a flebite durante o uso do CIP ao tempo de
permanencia do cateter e, com a flebite pos-infusao, a puncao em antebraco. Os
medicamentos Ceftriaxona, Claritromicina e Oxacilina foram associados a flebite
pos-infusao. CONCLUSOES: este estudo possibilitou investigar a associacao de
fatores de risco e a ocorrencia de flebites durante o uso e apos a retirada do
cateter. A frequencia da flebite pos-infusao foi maior do que o numero de
flebites durante a permanencia do cateter, sendo as de grau III e II,
respectivamente, as mais frequentes. Podem ser elucidados aspectos relacionados a
flebite pos-infusao, considerando-se poucos estudos abordam o tema sob esta
perspectiva. OBJETIVO: investigar la incidencia de flebitis y la asociacion de
factores de riesgo con su ocurrencia durante el uso y despues de la retirada del
cateter intravenoso periferico (CIP) (flebitis post-infusion) en adultos
hospitalizados. METODO: estudio de cohorte con 171 pacientes con CIP, totalizando
361 punciones. Fueron recolectadas variables sociodemograficas y relacionadas al
cateter. Analisis estadistico descriptivo y analitico. RESULTADOS: de los
pacientes, 51,5% eran hombres y el promedio de edad fue de 56,96 anos. La
incidencia de flebitis durante el uso del CIP fue de 1,25% y de post-infusion fue
de 1,38%. Se asocio la flebitis durante el uso del CIP al tiempo de permanencia
del cateter y con la post-infusion (puncion en el antebrazo). Los medicamentos
Ceftriaxona, Claritromicina y Oxacilina fueron asociados a la flebitis post
infusion. CONCLUSIONES: este estudio posibilito investigar la asociacion de
factores de riesgo y la ocurrencia de flebitis durante el uso y despues de la
retirada del cateter. La frecuencia de la flebitis post-infusion fue mayor que el
numero de flebitis asociada a la permanencia del cateter, siendo las de grado III
y II, respectivamente, las mas frecuentes. Se trato de elucidar aspectos
relacionados a la flebitis post-infusion, considerando que existen pocos estudios
que abordan el tema bajo esta perspectiva.
PMID- 27508917
TI - Effectiveness of personalized face-to-face and telephone nursing counseling
interventions for cardiovascular risk factors: a controlled clinical trial.
AB - OBJECTIVE: to evaluate the effect and gender differences of an innovative
intervention involving in-person and telephone nursing counseling to control
cardiovascular risk factors (arterial hypertension, dyslipidemia, and
overweight), improve health-related quality of life and strengthen self-efficacy
and social support in persons using the municipal health centers' cardiovascular
health program. METHOD: a randomized controlled clinical trial involving
participants randomized into the intervention group who received traditional
consultation plus personalized and telephone nursing counseling for 7 months (n =
53) and the control group (n = 56). The study followed the Consolidated Standards
of Reporting Trials Statement. RESULTS: women in the intervention group presented
a significant increase in the physical and mental health components compared to
the control group, with decreases in weight, abdominal circumference, total
cholesterol, low-density lipoprotein cholesterol, and the atherogenic index. The
effects attributable to the intervention in the men in the intervention group
were increased physical and emotional roles and decreased systolic and diastolic
pressure, waist circumference, total cholesterol, low-density lipoprotein
cholesterol, atherogenic index, cardiovascular risk factor, and 10-year coronary
risk. CONCLUSION: this intervention is an effective strategy for the control of
three cardiovascular risk factors and the improvement of health-related quality
of life.
PMID- 27508918
TI - Factors associated with mortality in patients undergoing coronary artery bypass
grafting.
AB - OBJECTIVE: to investigate the factors associated with mortality in patients
undergoing coronary artery bypass grafting in a cardiovascular referral hospital
in Santa Catarina. METHOD: quantitative, exploratory, descriptive and
retrospective study. The medical records of 1447 patients, from 2005 to 2013,
were analyzed for statistically related variables, these being: profile,
hospitalization diagnosis, risk factors for coronary artery disease,
complications recorded during the hospitalization, length of hospitalization and
cause of death. RESULTS: the mortality rate was 5.3% during the study period.
Death was more common in females and those of black skin color, with a mean age
of 65 years. Acute myocardial infarction was the most common hospitalization
diagnosis. The majority of the complications recorded during hospitalization were
characterized by changes in the cardiovascular system, with longer
hospitalization periods being directly related to death from septic shock.
CONCLUSION: the data provide subsidies for nursing work with preventive measures
and early detection of complications associated with coronary artery bypass
grafting. This reinforces the importance of using the data as quality indicators,
aiming to guarantee care guided by reliable information to guide managers in
planning patient care and high complexity health services.
PMID- 27508919
TI - Taking a look to promoting health and complications' prevention: differences by
context.
AB - OBJECTIVES: to acknowledge and compare the health promotion and complications'
prevention practices performed by nurses working in hospital and primary health
care contexts. METHODS: descriptive, exploratory and crosscutting study,
performed with 474 nurses selected by convenience sampling. It was used a form
that encompassed two categories of descriptive statements about quality in the
professional exercise of nurses. This study had ethical committee approval.
RESULTS: the nurses' population was mainly women (87,3%) with an average age of
35,5 years. There was more practices of the hospital's nurses related to the
identification of potential problems of the patient (p=0.001) and supervision of
the activities that put in place the nursing interventions and the activities
that they delegate (p=0.003). CONCLUSION: the nurses perform health promotion and
complications' prevention activities, however not in a systematic fashion and
professional practices differ by context. This study is relevant as it may
promote the critical consciousness of the nurses about the need of stressing
quality practices.
PMID- 27508920
TI - Social support of adults and elderly with chronic kidney disease on dialysis.
AB - OBJECTIVE: to evaluate the instrumental and emotional social support of patients
with chronic kidney disease on hemodialysis. METHOD: descriptive cross-sectional
study. The sample was sized for convenience and included 103 participants under
treatment in a Renal Replacement Therapy Unit. Data were collected through
individual interviews, using the Social Support Scale. RESULTS: the mean scores
of the emotional and instrumental social support were 3.92 (+/- 0.78) and 3.81
(+/- 0.69) respectively, an indication of good support received. The most
frequent sources of instrumental and emotional social support mentioned by
participants were partners, spouse, companion or boyfriend and friends.
CONCLUSION: patients with chronic kidney disease have high social support, both
instrumental and emotional, and the main support comes from the family.
PMID- 27508921
TI - Measurement of Family-centered care perception and parental stress in a neonatal
unit.
AB - OBJECTIVE: to evaluate the effects of the implementation of the Patient and
Family-Centered Care Model on parents and healthcare perceptions and parental
stress. METHOD: a quasi-experimental study developed in a neonatal unit of a
university hospital in the municipality of Sao Paulo, Brazil, with the
implementation of this model of care. Data collection were performed by two
sample groups, one using non-equivalent groups of parents, and another using
equivalent groups of healthcare professionals. The instruments Perceptions of
Family-Centered Care-Parent Brazilian Version, Perceptions of Family-Centered
Care-Staff Brazilian Version and Parental Stress Scale: Neonatal Intensive Care
Unit, were applied to 132 parents of newborns hospitalized and to 57
professionals. RESULTS: there was a statistically significant improvement in the
perceptions of the parents in most items assessed (p <=0,05) and for the staff in
relation to the family welcome in the neonatal unit (p = 0.041) and to the
comprehension of the family's experience with the infant's hospitalization (p =
0,050). There was a reduction in the average scores of parental stress, with a
greater decrease in the Alteration in Parental Role from 4,2 to 3,8 (p = 0,048).
CONCLUSION: the interventions improved the perceptions of parents and healthcare
team related to patient and family-centered care and contributed to reducing
parental stress. OBJETIVO: avaliar os efeitos da implementacao do Modelo do
Cuidado Centrado no Paciente e Familia na percepcao de pais e profissionais de
saude e no estresse parental. METODO: Estudo quase experimental com grupos nao
equivalentes para avaliacao dos efeitos da intervencao na percepcao de pais; e
com grupos equivalentes para a avaliacao na percepcao de profissionais de saude,
desenvolvido na unidade neonatal de um hospital universitario do municipio de Sao
Paulo. Os instrumentos, Percepcao do Cuidado Centrado na Familia- Pais versao
brasileira, Percepcao do Cuidado Centrado na Familia- Equipe versao brasileira e
Parental Stress Scale: Neonatal Intensive Care Unit, foram aplicados com 132 pais
de recem-nascidos internados e 57 profissionais da equipe. RESULTADOS: houve
melhora estatisticamente significante na percepcao dos pais na maioria dos itens
avaliados (p<=0,05) e para os profissionais em relacao ao acolhimento da familia
na unidade neonatal (p= 0,041) e a compreensao da vivencia da familia com a
hospitalizacao (p=0,050). Houve reducao dos escores medios do estresse parental,
com maior queda na Alteracao do Papel de Pais de 4,2 para 3,8 (p=0,048).
CONCLUSAO: as intervencoes realizadas melhoraram a percepcao de pais e de
profissionais da equipe de saude sobre o Cuidado Centrado no Paciente e Familia e
contribuiram para a reducao do estresse parental. OBJETIVO: evaluar los efectos
de la implementacion del Modelo del Cuidado Centrado en el Paciente y la Familia
en la percepcion de los padres y profesionales de la salud y en lo estres
parental. METODO: estudio cuasi-experimental con grupos no equivalentes para
evaluar los efectos de la intervencion en la percepcion de los padres; y grupos
equivalentes para evaluar la percepcion de los profesionales de la salud,
desarrollado en la unidad neonatal de un hospital universitario en el municipio
de Sao Paulo. Los instrumentos de Percepcion del Cuidado Centrado en el Paciente
y la Familia- Padres version brasilena, Percepcion del Cuidado Centrado en el
Paciente y la Familia-Equipo version brasilena y Parental Stress Scale: Neonatal
Intensive Care Unit, se aplicaron a 132 padres de los recien nacidos
hospitalizados y 57 profesional del equipo. RESULTADOS: se observo una mejoria
estadisticamente significativa en la percepcion de los padres en la mayoria de
los items evaluados (p = 0,05) y para los profesionales en relacion con el
cuidado de la familia en la unidad neonatal (p = 0,041) y la comprension de la
experiencia de la familia con la hospitalizacion (p = 0,050). Hubo una reduccion
en las puntuaciones medias de estres de los padres, con una mayor disminucion en
la Alteracion del Rol Parental 4.2 a 3.8 (p = 0,048). CONCLUSION: las
intervenciones mejoran la percepcion de los padres y los profesionales del equipo
de salud en el Cuidado Centrado en el Paciente y la Familia y ha contribuido a
reducir el estres de los padres.
PMID- 27508922
TI - Improvement of nursing students' learning outcomes through scenario-based skills
training.
AB - OBJECTIVE: this study analyzed the influence of scenario-based skills training on
students' learning skills. METHOD: the author evaluated the nursing skills
laboratory exam papers of 605 sophomores in nursing programs for seven years. The
study determined the common mistakes of students and the laboratory work was
designed in a scenario-based format. The effectiveness of this method was
evaluated by assessing the number of errors the students committed and their
achievement scores in laboratory examinations. This study presents the students'
common mistakes in intramuscular and subcutaneous injection and their development
of intravenous access skills, included in the nursing skills laboratory
examination. RESULTS: an analysis of the students' most common mistakes revealed
that the most common was not following the principles of asepsis for all three
skills (intramuscular, subcutaneous injection, intravenous access) in the first
year of the scenario-based training. The students' exam achievement scores
increased gradually, except in the fall semester of the academic year 2009-2010.
The study found that the scenario-based skills training reduced students' common
mistakes in examinations and enhanced their performance on exams. CONCLUSION:
this method received a positive response from both students and instructors. The
scenario-based training is available for use in addition to other skills training
methods.
PMID- 27508923
TI - Advanced practice nursing in Latin America and the Caribbean: regulation,
education and practice.
AB - OBJECTIVE: to identify the current state of advanced practice nursing regulation,
education and practice in Latin America and the Caribbean and the perception of
nursing leaders in the region toward an advanced practice nursing role in primary
health care to support Universal Access to Health and Universal Health Coverage
initiatives. METHOD: a descriptive cross-sectional design utilizing a web-based
survey of 173 nursing leaders about their perceptions of the state of nursing
practice and potential development of advanced practice nursing in their
countries, including definition, work environment, regulation, education, nursing
practice, nursing culture, and perceived receptiveness to an expanded role in
primary health care. RESULT: the participants were largely familiar with the
advanced practice nursing role, but most were unaware of or reported no current
existing legislation for the advanced practice nursing role in their countries.
Participants reported the need for increased faculty preparation and promotion of
curricula reforms to emphasize primary health care programs to train advanced
practice nurses. The vast majority of participants believed their countries'
populations could benefit from an advanced practice nursing role in primary
health care. CONCLUSION: strong legislative support and a solid educational
framework are critical to the successful development of advanced practice nursing
programs and practitioners to support Universal Access to Health and Universal
Health Coverage initiatives. OBJETIVO: identificar o estado atual da regulacao,
educacao e pratica do enfermeiro de pratica avancada na America Latina e no
Caribe e a percepcao de lideres de enfermagem na regiao quanto ao papel da
enfermagem de pratica avancada na atencao primaria a saude em apoio as
iniciativas de Acesso Universal a Saude e Cobertura Universal de Saude. METODO: o
estudo descritivo transversal utilizou um survey online com 173 lideres de
enfermagem questionando suas percepcoes sobre o estado atual da pratica de
enfermagem e o potencial desenvolvimento da enfermagem de pratica avancada em
seus paises, incluindo a definicao do termo, o ambiente de trabalho, a regulacao,
educacao, pratica, cultura de enfermagem e receptividade percebida de um papel
mais amplo deste profissional na atencao primaria a saude. RESULTADO: os
participantes referiram estar familiarizados com o papel do enfermeiro de pratica
avancada, mas a maioria nao sabia ou nao relatou a legislacao vigente para o
papel da pratica avancada em seus paises. Os participantes relataram a
necessidade de aumentar a preparacao do corpo docente e promover reformas
curriculares com enfase na atencao primaria a saude para formar enfermeiros de
pratica avancada. A grande maioria dos participantes acredita que as populacoes
de seus paises se beneficiara com o papel do enfermeiro de pratica avancada na
atencao primaria a saude. CONCLUSAO: forte apoio em termos de legislacao e uma
estrutura educacional solida de formacao continua sao fundamentais para o exito
do desenvolvimento de programas de enfermagem de pratica avancada em apoio as
iniciativas de Acesso Universal a Saude e Cobertura Universal de Saude. OBJETIVO:
identificar el estado actual de la regulacion, educacion y practica de la
enfermera de practica avanzada en Latinoamerica y el Caribe y la percepcion de
los lideres de enfermeria en la region hacia un rol de practica avanzada de
enfermeria dentro de la atencion primaria de salud para apoyar las iniciativas de
Acceso Universal a la Salud y la Cobertura Universal de Salud. METODO: un diseno
transversal descriptivo que utilizo una encuesta basada en la web a 173 lideres
de enfermeria acerca de sus percepciones sobre el estado de la enfermeria y el
desarrollo potencial de la practica avanzada de enfermeria en sus paises,
incluyendo definicion, ambiente laboral, regulacion, educacion, practica de
enfermeria, cultura de enfermeria y la receptividad percibida a un papel mas
amplio en atencion primaria de salud. RESULTADO: los participantes estaban
ampliamente familiarizados con el rol de la enfermera de practica avanzada, pero
la mayoria desconocia la legislacion o reportaba no existencia actual de
legislacion para el rol de practica avanzada en sus paises. Los participantes
reportaron la necesidad de aumentar la preparacion docente y reformas
curriculares para apoyar programas de atencion primaria de salud para capacitar
las enfermeras de practica avanzada. La gran mayoria de los participantes creian
que las poblaciones de sus paises se podrian beneficiar de un rol de practica
avanzada de enfermeria en atencion primaria de salud. CONCLUSION: un fuerte apoyo
legislativo y un marco educacional solido que continuen informandose entre si,
son criticos para el desarrollo exitoso de programas de practica avanzada y de
nurse practitioners para apoyar las iniciativas de Acceso Universal a la Salud y
Cobertura Universal de Salud.
PMID- 27508924
TI - Zero to 50,000 - The 20th Anniversary of the Hospitalist.
PMID- 27508925
TI - Nanostructured Aptamer-Functionalized Black Phosphorus Sensing Platform for Label
Free Detection of Myoglobin, a Cardiovascular Disease Biomarker.
AB - We report the electrochemical detection of the redox active cardiac biomarker
myoglobin (Mb) using aptamer-functionalized black phosphorus nanostructured
electrodes by measuring direct electron transfer. The as-synthesized few-layer
black phosphorus nanosheets have been functionalized with poly-l-lysine (PLL) to
facilitate binding with generated anti-Mb DNA aptamers on nanostructured
electrodes. This aptasensor platform has a record-low detection limit (~0.524 pg
mL(-1)) and sensitivity (36 MUA pg(-1) mL cm(-2)) toward Mb with a dynamic
response range from 1 pg mL(-1) to 16 MUg mL(-1) for Mb in serum samples. This
strategy opens up avenues to bedside technologies for multiplexed diagnosis of
cardiovascular diseases in complex human samples.
PMID- 27508926
TI - Synthesis of Cyclic Peptidomimetics via a Pd-Catalyzed Macroamination Reaction.
AB - A new method to access cyclic peptidomimetics via a Pd-catalyzed macroamination
reaction is presented. Natural amino acid amines are revealed as proficient
coupling partners in these transformations. With a commercially available CPhos
G3 catalyst system and substrates bearing diverse amino acid and aryl halide
backbones, the unique head to side-chain (or side-chain mimic) macrocycles are
afforded with ring sizes from 11 to 23 members in yields up to 84%.
PMID- 27508927
TI - Predictive Factors for Excellent or Extremely Poor Functional Outcome in Initial
Atrial Fibrillation-Related Cardioembolic Stroke.
AB - BACKGROUND: We aimed to determine the predictive factors for excellent or
extremely poor functional outcome in patients with first-ever atrial fibrillation
(AF)-related cardioembolic stroke. METHODS: Retrospective observational study
from a database. Patients with AF-related cardioembolic stroke with a premorbid
modified Rankin Scale (mRS) score of 0 or 1 and without a previous history of
stroke were included. RESULTS: Factors associated with excellent functional
outcome (mRS scores of 0 or 1; n = 77; 30.4% of patients) included age >78 years
(OR 0.31, 95% CI 0.15-0.61), male sex (OR 2.16, 95% CI 1.04-4.60), absence of
hypertension (OR 0.46, 95% CI 0.22-0.94) and initial National Institutes of
Health Stroke Scale (NIHSS) score of >9 (OR 0.08, 95% CI 0.03-0.16). Factors
associated with extremely poor functional outcome (mRS scores of 5 or 6; n = 63;
24.9%) included age >78 years (OR 3.30, 95% CI 1.54-7.39), initial NIHSS score of
>9 (OR 12.38, 95% CI 5.40-32.56), congestive heart failure (OR 4.82, 95% CI 2.00
12.19) and ischemic heart disease (OR 4.02, 95% CI 1.18-14.69). CONCLUSIONS:
Predictive factors exist to delineate excellent and extremely poor functional
outcomes after a first-time stroke associated with AF.
PMID- 27508928
TI - Correction: Effect of Chronic Athletic Activity on Brown Fat in Young Women.
AB - [This corrects the article DOI: 10.1371/journal.pone.0156353.].
PMID- 27508929
TI - The Motor Subsystem as a Predictor of Success in Young Football Talents: A Person
Oriented Study.
AB - Motor tests play a key role in talent selection in football. However, individual
motor tests only focus on specific areas of a player's complex performance. To
evaluate his or her overall performance during a game, the current study takes a
holistic perspective and uses a person-oriented approach. In this approach,
several factors are viewed together as a system, whose state is analysed
longitudinally. Based on this idea, six motor tests were aggregated to form the
Motor Function subsystem. 104 young, top-level, male football talents were tested
three times (2011, 2012, 2013; Mage, t2011 = 12.26, SD = 0.29), and their overall
level of performance was determined one year later (2014). The data were analysed
using the LICUR method, a pattern-analytical procedure for person-oriented
approaches. At all three measuring points, four patterns could be identified,
which remained stable over time. One of the patterns found at the third measuring
point identified more subsequently successful players than random selection
would. This pattern is characterised by above-average, but not necessarily the
best, performance on the tests. Developmental paths along structurally stable
patterns that occur more often than predicted by chance indicate that the Motor
Function subsystem is a viable means of forecasting in the age range of 12-15
years. Above-average, though not necessary outstanding, performance both on
fitness and technical tests appears to be particularly promising. These findings
underscore the view that a holistic perspective may be profitable in talent
selection.
PMID- 27508931
TI - Overexpression of Hypo-Phosphorylated IkappaBbeta at Ser313 Protects the Heart
against Sepsis.
AB - IkappaBbetais an inhibitor of nuclear factor kappa B(NF-kappaB) and participates
in the cardiac response to sepsis. However, the role of the hypo-phosphorylated
form of IkappaBbeta at Ser313, which can be detected during sepsis, is unknown.
Here, we examined the effects of IkappaBbeta with a mutation at Ser313->Ala313 on
cardiac damage induced by sepsis. Transgenic (Tg) mice were generated to
overexpress IkappaBbeta, in which Ser-313 is replaced with alanine ubiquitously,
in order to mimic the hypo-phosphorylated form of IkappaBbeta. Survival analysis
showed that Tg mice exhibited decreased inflammatory cytokine levels and
decreased rates of mortality in comparison to wild type (WT) mice, after sepsis
in a cecal-ligation and puncture model (CLP). Compared to WT septic mice, sepsis
in Tg mice resulted in improved cardiac functions, lower levels of troponin I and
decreased rates of cardiomyocyte apoptosis, compared to WT mice. The increased
formation of autophagicvacuoles detected with electron microscopy demonstrated
the enhancement of cardiac autophagy. This phenomenon was further confirmed by
the differential expression of genes related to autophagy, such as LC3, Atg5,
Beclin-1, and p62. The increased expression of Cathepsin L(Ctsl), a specific
marker for mitochondrial stress response, may be associated with the beneficial
effects of the hypo-phosphorylated form of IkappaBbeta. Our observations suggest
that the hypo-phosphorylated form of IkappaBbeta at Ser313 is beneficial to the
heart in sepsis through inhibition of apoptosisand enhancement of autophagy in
mutated IkappaBbeta transgenic mice.
PMID- 27508932
TI - Do Dogs Provide Information Helpfully?
AB - Dogs are particularly skilful during communicative interactions with humans.
Dogs' abilities to use human communicative cues in cooperative contexts
outcompete those of other species, and might be the result of selection pressures
during domestication. Dogs also produce signals to direct the attention of humans
towards outside entities, a behaviour often referred to as showing behaviour.
This showing behaviour in dogs is thought to be something dogs use intentionally
and referentially. However, there is currently no evidence that dogs communicate
helpfully, i.e. to inform an ignorant human about a target that is of interest to
the human but not to the dog. Communicating with a helpful motive is particularly
interesting because it might suggest that dogs understand the human's goals and
need for information. In study 1, we assessed whether dogs would abandon an
object that they find interesting in favour of an object useful for their human
partner, a random novel distractor, or an empty container. Results showed that it
was mainly self-interest that was driving the dogs' behaviour. The dogs mainly
directed their behaviour towards the object they had an interest in, but dogs
were more persistent when showing the object relevant to the human, suggesting
that to some extent they took the humans interest into account. Another
possibility is that dogs' behaviour was driven by an egocentric motivation to
interact with novel targets and that the dogs' neophila might have masked their
helpful tendencies. Therefore, in study 2 the dogs had initial access to both
objects, and were expected to indicate only one (relevant or distractor). The
human partner interacted with the dog using vocal communication in half of the
trials, and remaining silent in the other half. Dogs from both experimental
groups, i.e. indicating the relevant object or indicating the distractor,
established joint attention with the human. However, the human's vocal
communication and the presence of the object relevant to the human increased the
persistency of showing, supporting the hypothesis that the dogs understood the
objects' relevance to the human. We propose two non-exclusive explanations. These
results might suggest that informative motives could possibly underlie dogs'
showing. It is also possible that dogs might have indicated the location of the
hidden object because they recognised it as the target of the human's search.
This would be consistent with taking into account the objects' relevance, without
necessarily implying that the dogs understood the human's state of knowledge.
PMID- 27508933
TI - Climate Response of Tree Radial Growth at Different Timescales in the Qinling
Mountains.
AB - The analysis of the tree radial growth response to climate is crucial for
dendroclimatological research. However, the response relationships between tree
ring indices and climatic factors at different timescales are not yet clear. In
this study, the tree-ring width of Huashan pine (Pinus armandii) from Huashan in
the Qinling Mountains, north-central China, was used to explore the response
differences of tree growth to climatic factors at daily, pentad (5 days), dekad
(10 days) and monthly timescales. Correlation function and linear regression
analysis were applied in this paper. The tree-ring width showed a more sensitive
response to daily and pentad climatic factors. With the timescale decreasing, the
absolute value of the maximum correlation coefficient between the tree-ring data
and precipitation increases as well as temperature (mean, minimum and maximum
temperature). Compared to the other three timescales, pentad was more suitable
for analysing the response of tree growth to climate. Relative to the monthly
climate data, the association between the tree-ring data and the pentad climate
data was more remarkable and accurate, and the reconstruction function based on
the pentad climate was also more reliable and stable. We found that the major
climatic factor limiting Huashan pine growth was the precipitation of pentads 20
35 (from April 6 to June 24) rather than the well-known April-June precipitation.
The pentad was also proved to be a better timescale for analysing the climate and
tree growth in the western and eastern Qinling Mountains. The formation of the
earlywood density of Chinese pine (Pinus tabulaeformis) from Shimenshan in
western Qinling was mainly affected by the maximum temperature of pentads 28-32
(from May 16 to June 9). The maximum temperature of pentads 28-33 (from May 16 to
June 14) was the major factor affecting the ring width of Chinese pine from
Shirenshan in eastern Qinling.
PMID- 27508930
TI - Lipophosphoglycans from Leishmania amazonensis Strains Display Immunomodulatory
Properties via TLR4 and Do Not Affect Sand Fly Infection.
AB - The immunomodulatory properties of lipophosphoglycans (LPG) from New World
species of Leishmania have been assessed in Leishmania infantum and Leishmania
braziliensis, the causative agents of visceral and cutaneous leishmaniasis,
respectively. This glycoconjugate is highly polymorphic among species with
variation in sugars that branch off the conserved Gal(beta1,4)Man(alpha1)-PO4
backbone of repeat units. Here, the immunomodulatory activity of LPGs from
Leishmania amazonensis, the causative agent of diffuse cutaneous leishmaniasis,
was evaluated in two strains from Brazil. One strain (PH8) was originally
isolated from the sand fly and the other (Josefa) was isolated from a human case.
The ability of purified LPGs from both strains was investigated during in vitro
interaction with peritoneal murine macrophages and CHO cells and in vivo
infection with Lutzomyia migonei. In peritoneal murine macrophages, the LPGs from
both strains activated TLR4. Both LPGs equally activate MAPKs and the NF-kappaB
inhibitor p-IkappaBalpha, but were not able to translocate NF-kappaB. In vivo
experiments with sand flies showed that both stains were able to sustain
infection in L. migonei. A preliminary biochemical analysis indicates
intraspecies variation in the LPG sugar moieties. However, they did not result in
different activation profiles of the innate immune system. Also those
polymorphisms did not affect infectivity to the sand fly.
PMID- 27508935
TI - Objective assessment of compliance with intra- and extraoral removable
appliances.
AB - OBJECTIVE: To conduct an objective assessment of the level of compliance in young
patients prescribed various types of removable appliances and to determine the
influence of device type, treatment duration, and patient age, gender,
psychological maturity, and awareness of monitoring on compliance. MATERIALS AND
METHODS: A total of 30 patients were fitted with either a class 2 (Frankel or
bionator) or a class 3 (face mask) removable appliance, each bearing a compliance
indicator chip, and they were instructed to wear them for 13 hours per day.
Compliance was monitored by means of the sensor for an average of 8 months. Of
the patients, 14 were informed that their appliance was fitted with a monitoring
sensor, and 16 were not. The psychological maturity of all patients was assessed
on the Nowicki-Strickland Locus of Control Scale, and the effect on compliance of
this score as well as the patient- and treatment-related variables considered
were determined via statistical analysis Results: The mean compliance recorded by
the chips was 8.6 +/- 2.9 hours, far lower than the 13 hours prescribed, and
younger patients showed significantly greater compliance than adolescents (P <
.01). However, no significant differences in compliance were found between intra-
and extraoral appliances, and neither gender, psychological scores, treatment
duration, nor awareness of being monitored had any significant effect.
CONCLUSIONS: Compliance is generally very poor in young patients, regardless of
their gender and psychological maturity. Although awareness of monitoring does
not appear to boost compliance, such systems may be a valuable means of providing
a dentist with objective information regarding their patients' compliance.
PMID- 27508934
TI - Transcriptome Analysis Reveals Regulation of Gene Expression for Lipid Catabolism
in Young Broilers by Butyrate Glycerides.
AB - BACKGROUND & AIMS: Butyrate has been shown to potently regulate energy
expenditure and lipid metabolism in animals, yet the underlying mechanisms remain
to be fully understood. The aim of this study was to investigate the molecular
mechanisms of butyrate (in the form of butyrate glycerides, BG)-induced lipid
metabolism at the level of gene expression in the jejunum and liver of broilers.
METHODOLOGY/PRINCIPAL FINDINGS: Two animal experiments were included in this
study. In Experiment 1, two hundred and forty male broiler chickens were equally
allocated into two groups: 1) basal diet (BD), 2) BG diets (BD + BG). Growth
performance was compared between treatments for the 41-day trial. In Experiment
2, forty male broiler chickens were equally allocated into two groups. The
general experimental design, group and management were the same as described in
Experiment 1 except for reduced bird numbers and 21-day duration of the trial.
Growth performance, abdominal fat deposition, serum lipid profiles as well as
serum and tissue concentrations of key enzymes involved in lipid metabolism were
compared between treatments. RNA-seq was employed to identify both differentially
expressed genes (DEGs) and treatment specifically expressed genes (TSEGs).
Functional clustering of DEGs and TSEGs and signaling pathways associated with
lipid metabolism were identified using Ingenuity Pathways Analysis (IPA) and
DAVID Bioinformatics Resources 6.7 (DAVID-BR). Quantitative PCR (qPCR) assays
were subsequently conducted to further examine the expression of genes in the
peroxisome proliferator-activated receptors (PPAR) signaling pathway identified
by DAVID-BR. Dietary BG intervention significantly reduced abdominal fat ratio
(abdominal fat weight/final body weight) in broilers. The decreased fat
deposition in BG-fed chickens was in accordance with serum lipid profiles as well
as the level of lipid metabolism-related enzymes in the serum, abdominal adipose,
jejunum and liver. RNA-seq analysis indicated that dietary BG intervention
induced 79 and 205 characterized DEGs in the jejunum and liver, respectively. In
addition, 255 and 165 TSEGs were detected in the liver and jejunum of BG-fed
group, while 162 and 211 TSEGs genes were observed in the liver and jejunum of BD
fed birds, respectively. Bioinformatic analysis with both IPA and DAVID-BR
further revealed a significant enrichment of DEGs and TSEGs in the biological
processes for reducing the synthesis, storage, transportation and secretion of
lipids in the jejunum, while those in the liver were for enhancing the oxidation
of ingested lipids and fatty acids. In particular, transcriptional regulators of
THRSP and EGR-1 as well as several DEGs involved in the PPAR-alpha signaling
pathway were significantly induced by dietary BG intervention for lipid
catabolism. CONCLUSIONS: Our results demonstrate that BG reduces body fat
deposition via regulation of gene expression, which is involved in the biological
events relating to the reduction of synthesis, storage, transportation and
secretion, and improvement of oxidation of lipids and fatty acids.
PMID- 27508936
TI - Different Contributions of Physical Activity on Arterial Stiffness between
Diabetics and Non-Diabetics.
AB - BACKGROUND: We compared the contribution of physical activity to the change in
arterial stiffness between patients with and without diabetes in ischemic heart
disease. METHODS: We studied 96 (diabetes) and 109 (without diabetes) patients
with ischemic heart disease treated by percutaneous coronary intervention (PCI).
Arterial stiffness was assessed by cardio-ankle vascular index (CAVI) at the
first diagnosis of significant coronary ischemia and 6 months after PCI and
optimal medical therapy. Physical activity was evaluated using the long form of
the International Physical Activity Questionnaire (IPAQ). RESULTS: CAVI values
increased more for diabetic patients than for non-diabetic. The IPAQ scores did
not differ between the two groups. During follow-up, CAVI values did not
significantly change in either group. In diabetic patients, the CAVI score for 48
patients did not change (NC-group) and 48 patients improved (Improved-group).
Physical activity scores were 937.9 +/- 923.2 and 1524.6 +/- 1166.2 in the NC-
and Improved-groups, respectively. IPAQ scores and uric acid levels significantly
affect CAVI improvement after adjusting for age, sex, baseline CAVI, total
cholesterol, and estimated glomerular filtration rate. CONCLUSION: Determining
factors influencing CAVI improvement during follow-up were significantly
different between patients with and without diabetes. IPAQ scores and uric acid
levels were significantly correlated with CAVI changes.
PMID- 27508937
TI - Tailored Therapist-Guided Internet-Based Cognitive Behavioral Treatment for
Psoriasis: A Randomized Controlled Trial.
AB - OBJECTIVE: Patients with somatic conditions, such as psoriasis, frequently suffer
from high burden of their disease in daily life and might benefit from internet
based cognitive behavioral therapy (ICBT) tailored to their adjustment problems.
The aim of this multicenter randomized controlled trial was to examine the
effects of therapist-guided, individually tailored ICBT in a clinical sample of
patients with psoriasis. METHODS: A total of 131 patients with psoriasis, who
were screened for a psychological risk profile, were randomized to either care as
usual (CAU, n = 66) or ICBT in addition to CAU (n = 65). Participants filled out
standardized self-report questionnaires assessing physical and psychological
functioning and impact on daily activities at baseline, posttreatment assessment,
and 6-month follow-up. RESULTS: In covariate-controlled linear mixed-model
analyses, significantly larger improvements in ICBT compared to CAU were found in
the primary outcomes physical functioning (p = 0.03, d = 0.36) and impact on
daily activities (p = 0.04, d = 0.35), but not in psychological functioning (p =
0.32), up to 6 months after treatment compared to baseline. In explorative
analyses, the working alliance measured at the beginning of ICBT treatment
predicted improved physical (p = 0.02) and psychological (p < 0.001) outcomes.
CONCLUSIONS: Results underline the promise of therapist-guided, individually
tailored ICBT to improve physical functioning and reduce the impact of psoriasis
on daily activities in patients with a psychological risk profile. Establishing a
good therapeutic relationship early on may be an important factor that influences
treatment outcomes in personalized ICBT interventions. Further research is needed
to evaluate ICBT effectiveness in additional samples and to explore its
underlying mechanisms.
PMID- 27508938
TI - An integrative review of how families are prepared for, and supported during
withdrawal of life-sustaining treatment in intensive care.
AB - AIM: The aim of this study was to conduct an integrative review on how nurses
prepare families for and support families during withdrawal of life-sustaining
treatments in intensive care. BACKGROUND: End-of-life care is widely acknowledged
as integral to the practice of intensive care. However, little is known about
what happens after the decision to withdraw life-sustaining treatments has been
made and how families are prepared for death and the dying process. DESIGN:
Integrative literature review. DATA SOURCES: MEDLINE, CINAHL Plus, PsychINFO,
PUBMED, Scopus, EMBASE and Web of Knowledge were searched for papers published
between 2000-May 2015. REVIEW METHODS: A five stage review process, informed by
Whittemore and Knafl's methodology was conducted. All papers were reviewed and
quality assessment performed. Data were extracted, organized and analysed.
Convergent qualitative thematic synthesis was used. RESULTS: From an identified
479 papers, 24 papers were included in this review with a range of research
approaches: qualitative (n = 15); quantitative (n = 4); mixed methods (n = 2);
case study (n = 2) and discourse analysis (n = 1). Thematic analysis revealed the
nurses: equipped families for end of life through information provision and
communication; managed the withdrawal of life-sustaining treatments to meet
family need; and continued care to build memories. CONCLUSION: Greater
understanding is needed of the language that can be used with families to
describe death and dying in intensive care. Clearer conceptualization of the
relationship between the medically focussed withdrawal of life-sustaining
treatments and patient/family-centred end-of-life care is required making the
nursing contribution at this time more visible.
PMID- 27508939
TI - Baseline characteristics, chromosomal alterations, and treatment affecting
prognosis of deletion 17p in newly diagnosed myeloma.
AB - Deletion 17p13, del(17p), is associated with poor outcome in myeloma but some
patients show long-term survival. With the current study we intended to identify
factors impacting outcome of such high risk patients. We analyzed 110 newly
diagnosed, symptomatic patients with del(17p) detected by fluorescence in situ
hybridization (FISH) in CD138-purified myeloma cells to identify prognostic
factors for survival. Age >65 years, ISS III, and elevated LDH negatively
impacted survival. Patients with subclonal (10-60% of plasma cells) del(17p) had
longer progression-free survival (PFS) than patients with del(17p) in >60% of
plasma cells (26 vs. 19 months, P = 0.03). Additional gain of 1q21 was associated
with shorter PFS (17 vs. 25 months, P = 0.01). Hyperdiploidy did not ameliorate
impact of del(17p), but gain 19q13 predicted longer PFS (30 vs. 18 months, P =
0.01) and overall survival (50 vs. 29 months, P = 0.01). Multivariate analysis in
transplant eligible patients (<=65 years) revealed better survival for patients
treated with upfront autologous transplantation (hazard ratio, [95% confidence
interval]: 0.15 [0.04, 0.58], P = 0.006). Application of maintenance therapy was
associated with better survival in transplant-eligible patients (0.30 [0.09,
0.99], P = 0.05). We demonstrate heterogeneous outcome of patients with del(17p)
according to baseline characteristics and treatment. 19q13 should be included in
routine FISH panel, since gains were associated with better survival. Am. J.
Hematol. 91:E473-E477, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27508940
TI - Pneumococcal lipoproteins involved in bacterial fitness, virulence, and immune
evasion.
AB - Streptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to
survive in several niches within the human body either as a harmless commensal or
as a serious pathogen causing a variety of diseases. The dynamic interaction
between pneumococci and resident host cells during colonization of the upper
respiratory tract and at the site of infection is critical for bacterial survival
and the development of disease. Pneumococcal lipoproteins are peripherally
anchored membrane proteins and have pivotal roles in bacterial fitness including
envelope stability, cell division, nutrient acquisition, signal transduction,
transport (as substrate-binding proteins of ABC transporter systems), resistance
to oxidative stress and antibiotics, and protein folding. In addition,
lipoproteins are directly involved in virulence-associated processes such as
adhesion, colonization, and persistence through immune evasion. Conversely,
lipoproteins are also targets for the host response both as ligands for toll-like
receptors and as targets for acquired antibodies. This review summarizes the
multifaceted roles of selected pneumococcal lipoproteins and how this knowledge
can be exploited to combat pneumococcal infections.
PMID- 27508941
TI - Intrinsic protein disorder could be overlooked in cocrystallization conditions:
An SRCD case study.
AB - X-ray diffractometry dominates protein studies, as it can provide 3D structures
of these diverse macromolecules or their molecular complexes with interacting
partners: substrates, inhibitors, and/or cofactors. Here, we show that under
cocrystallization conditions the results could reflect induced protein folds
instead of the (partially) disordered original structures. The analysis of
synchrotron radiation circular dichroism spectra revealed that the Im7 immunity
protein stabilizes the native-like solution structure of unfolded NColE7 nuclease
mutants via complex formation. This is consistent with the fact that among the
several available crystal structures with its inhibitor or substrate, all NColE7
structures are virtually the same. Our results draw attention to the possible
structural consequence of protein modifications, which is often hidden by
compensational effects of intermolecular interactions. The growing evidence on
the importance of protein intrinsic disorder thus, demands more extensive
complementary experiments in solution phase with the unligated form of the
protein of interest.
PMID- 27508942
TI - Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization
and Pathology: Closer to Proving Koch's Postulates.
AB - Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic
protists that inhabit the gastrointestinal tract. Although Blastocystis spp. have
been associated with gastrointestinal symptoms, irritable bowel syndrome and
urticaria, their clinical significance has remained controversial. We established
an ex vivo mouse explant model to characterize adhesion in the context of tissue
architecture and presence of the mucin layer. Using confocal microscopy with
tissue whole mounts and two axenic isolates of Blastocystis spp., subtype 7 with
notable differences in adhesion to intestinal epithelial cells (IEC), isolate B
(ST7-B) and isolate H (more adhesive, ST7-H), we showed that adhesion is both
isolate dependent and tissue trophic. The more adhesive isolate, ST7-H was found
to bind preferentially to the colon tissue than caecum and terminal ileum. Both
isolates were also found to have mucinolytic effects. We then adapted a DSS
colitis mouse model as a susceptible model to study colonization and acute
infection by intra-caecal inoculation of trophic Blastocystis spp.cells. We found
that the more adhesive isolate ST7-H was also a better colonizer with more mice
shedding parasites and for a longer duration than ST7-B. Adhesion and
colonization was also associated with increased virulence as ST7-H infected mice
showed greater tissue damage than ST7-B. Both the ex vivo and in vivo models used
in this study showed that Blastocystis spp. remain luminal and predominantly
associated with mucin. This was further confirmed using colonic loop experiments.
We were also successfully able to re-infect a second batch of mice with ST7-H
isolates obtained from fecal cultures and demonstrated similar histopathological
findings and tissue damage thereby coming closer to proving Koch's postulates for
this parasite.
PMID- 27508943
TI - Evaluation of grape pomace from red wine by-product as feed for sheep.
AB - BACKGROUND: This work aimed to study the chemical composition and in vitro
digestibility of seeds and pulp from grape pomace. In sacco degradability,
ruminal fermentation of grape pomace fractions and plasma lipid peroxidation were
also studied in sheep fed with or without grape pomace. RESULTS: Seed and pulp
fractions of grape pomace had different values for cell walls (523 vs 243 g kg-1
dry matter (DM)), crude protein (CP, 104 vs 138 g kg-1 DM), ether extract (EE,
99.0 vs 31.7 g kg-1 DM), polyunsaturated fatty acids (PUFA, 69.6 vs 53.3%) and
extractable polyphenols (55.0 vs 32.1 g kg-1 DM). The in vitro true
digestibility, DM in sacco degradability and CP degradability of seeds and pulp
were also different (0.51 vs 0.82, 0.30 vs 0.45 and 0.66 vs 0.39 respectively).
The ammonia-N concentration and total volatile fatty acids (VFA) in ruminal
liquid were significantly lower and plasma lipid peroxidation was also
numerically lower in sheep that consumed grape pomace. CONCLUSION: The nutritive
value of grape pomace varies depending on the proportion of seeds and pulp. The
interest of this by-product in sheep feeding could be related to its polyphenol
and PUFA content, which could improve meat and milk quality. (c) 2016 Society of
Chemical Industry.
PMID- 27508944
TI - Management of Late Seroma in Patients with Breast Implants: The Role of the
Radiologists.
PMID- 27508945
TI - Determinants of the Intention to Pump Breast Milk on a University Campus.
AB - INTRODUCTION: The number of young mothers in the workforce and in schools of
higher education has steadily increased. In order to maintain a breastfeeding
relationship with their children, these mothers need to pump or express breast
milk multiple times a day while at work or school. This study examines the
factors associated with the intention to pump breast milk at one university
campus. METHODS: Between January and February 2015, an online survey invitation
was sent out to all female employees and students at one university. The survey,
based on the Theory of Planned Behavior, assessed intentions to pump breast milk
on campus. The intention to pump breast milk was examined between employees and
students separately. Within these 2 groups, behavioral performers (women who pump
or have pumped breast milk while on campus) were compared to nonperformers. Using
multiple regression analysis, the most influential predictors of the intention to
pump (ie, attitudes, subjective norm, perceived behavioral control, and
underlying beliefs) were identified. RESULTS: A total of 218 women participated
in the study (62 employees and 156 students, a 71.7% survey completion rate).
Among university employees, the most influential factor that predicted pumping
intention among performers was attitude toward pumping (beta = 0.36, P = .03).
Among student performers, the most influential factor to predict pumping
intention was the subjective norm (beta = 0.31, P = .02). For student
nonperformers, perceived behavioral control (beta = 0.54, P < .001) was the most
influential factor. Important determinants of the intention to pump on campus
included relieving discomfort from engorgement, availability of milk storage,
experiencing other people's approval of pumping breast milk, and the
inconvenience of carrying pump equipment. DISCUSSION: Continued efforts are
needed to create a supportive culture for breastfeeding in the campus community
as well as to provide pump loan and milk storage options for both employee and
student mothers.
PMID- 27508946
TI - Population-based study of ruptured abdominal aortic aneurysm.
AB - BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) and their rupture
has been reported to be decreasing. The aim was to evaluate trends in ruptured
AAA (rAAA) incidence in the hospital district of Helsinki and Uusimaa (HUS) in
southern Finland. This was a population-based retrospective review of all
patients with rAAA in this well defined geographical area during 2003-2013.
METHODS: Data for all patients treated for rAAA at Helsinki University Hospital,
the only vascular surgery centre in an area of 1.5 million inhabitants, were
collected from local vascular registry. All deaths attributed to rAAA were
obtained from the cause of death registry of Statistics Finland. RESULTS: The
mean(s.d.) age of the 712 patients with rAAA was 76.5(9.6) years; 76.7 per cent
of them were men. Only 330 patients (46.3 per cent of those with rAAA) arrived
alive at Helsinki University Hospital. The turn-down rate for surgical treatment
was 10.3 per cent. Of the 296 patients operated on, 199 (67.2 per cent) were
alive at 30 days. Only 27.9 per cent of all patients were alive 30 days after
rupture of the AAA. The incidence of rAAA was 4.3 per 100 000 inhabitants and the
mortality rate was 3.2 per 100 000 inhabitants. A decreasing trend was seen in
incidence and mortality during the 11-year study interval. CONCLUSION: The
incidence of rAAA is decreasing in the HUS district. Mortality from rAAA remains
very high, because half of the patients die before reaching the hospital.
PMID- 27508947
TI - Distinguishing malignant and benign renal masses with composite models and
nomograms: A systematic review and meta-analysis of clinically localized renal
masses suspicious for malignancy.
AB - Solid renal masses and cystic lesions with solid components are suspicious for
renal cell carcinoma. Without an effective screening test, composite models and
nomograms rely on patient and tumor characteristics to stratify the risk of
benign disease versus malignant disease. To guide decisions about the use of
renal mass sampling or excision, a systematic review and meta-analysis of the
ability of composite models to predict the likelihood of malignancy on the basis
of preoperative clinical variables was performed. MEDLINE, EMBASE, and the
Cochrane Central Register of Controlled Trials were searched from January 1,
1997, through May 1, 2015, according to the Preferred Reporting Items for
Systematic Review and Meta-Analyses statement. Composite models necessarily
included imaging results and at least 1 element from the following to be compared
with surgical pathology: demographic characteristics, clinical characteristics,
and blood or urine tests. Two independent reviewers screened citations and
extracted data. Quality Assessment Tool for Diagnostic Accuracy Studies 2 was
used to assess the risk of bias. The strength of evidence was graded with the
scheme recommended by Methods Guide for Effectiveness and Comparative
Effectiveness Reviews. Twenty studies (12,149 patients) were included in this
review. The only significant predictors of malignancy in the composite models
were tumor size (effect size, 1.33-fold increased risk per centimeter; 95%
confidence interval [CI], 1.22-1.43) and male sex (effect size, 2.71; 95% CI,
2.39-3.02). The results were inconclusive or not significant for tumor
characteristics, age, body mass index, and incidental presentation. In
conclusion, composite models currently have a limited ability to distinguish
malignant renal masses from benign renal masses, with increased tumor size and
male sex associated with malignancy. Cancer 2016;122:3267-3276. (c) 2016 American
Cancer Society.
PMID- 27508948
TI - COMPARISON OF THE LAMINA CRIBROSA THICKNESS OF PATIENTS WITH UNILATERAL BRANCH
RETINAL VEIN OCCLUSION AND HEALTHY SUBJECTS.
AB - PURPOSE: To compare the lamina cribrosa (LC) thickness of healthy subjects and
patients with unilateral branch retinal vein occlusion (BRVO), and to determine
possible correlations between the LC thickness and the BRVO subtypes. METHODS:
This prospective, cross-sectional study included a total of 46 patients with
naive, untreated, unilateral BRVO and 31 healthy control subjects. The occlusion
site was divided into two BRVO types: arteriovenous crossing BRVO (AV-BRVO) and
optic nerve BRVO (ON-BRVO). The optic nerve head was scanned using enhanced-depth
imaging with the Spectralis optical coherence tomography system. RESULTS: The
mean LC thickness of both eyes in patients with BRVO was thinner than that of
eyes (274.0 MUm) of the healthy subjects (both, P < 0.001). Although the LC
thickness of the BRVO-affected eyes was slightly thinner than that of the fellow
eyes (237.0 MUm vs. 241.4 MUm, respectively), there was no statistically
significant difference. In addition, there were no significant differences in the
LC thicknesses of both eyes according to the site of occlusion. CONCLUSION: A
thinner LC was observed in both eyes of unilateral BRVO patients compared with
those of healthy subjects. This finding suggests that thin LC may contribute to
the pathogenesis of BRVO as a local mechanical factor in addition to systemic
factors.
PMID- 27508949
TI - The positive predictive value of "suspicious for high-grade urothelial carcinoma"
in urinary tract cytology specimens: A single-institution study of 665 cases.
AB - BACKGROUND: "The Paris System" proposes a 7-tier classification system for urine
cytology. Establishing the risk of malignancy (ROM) associated with these
diagnostic categories is essential to determine the appropriate management of
patients. The objective of this study was to determine the ROM associated with
the "positive" and "suspicious" categories. METHODS: The authors searched their
electronic records for urine cytology specimens that had been diagnosed as
"positive" or "suspicious" for high-grade urothelial carcinoma within an 11-year
time frame. Then, the ROM was determined for these specimens within a 6-month
follow-up interval. The cytologic diagnoses were correlated with surgical biopsy
results, follow-up cytology results, and/or fluorescence in situ hybridization
(FISH) results. RESULTS: In total, 662 specimens (487 "positive" and 175
"suspicious"), corresponding to 387 patients (295 men and 92 women), were
included. The majority of specimens were collected by bladder washing (568 of 662
specimens; 85.4%) and for the indication of surveillance (601 of 662 specimens;
82%). On follow-up, bladder washing specimens were positive more often positive
than voided urine specimens (466 of 570 [81.8%] vs 60 of 92 [65.2%]; P = .0005),
and surveillance specimens were more often positive than specimens collected for
other indications (82% vs 54.1%). The overall positive predictive value was
higher for positive specimens than for suspicious specimens (365 of 461 [79.2%]
vs 83 of 150 [55.3%]; P < .0001). CONCLUSIONS: Diagnoses of suspicious for high
grade urothelial carcinoma, as used at the authors' institution, have an ROM that
is high but is lower than that for the "positive" category. Therefore, the
authors suggest keeping the 2 categories separate, although management should be
aggressive in both groups. Cancer Cytopathol 2016;124:811-9. (c) 2016 American
Cancer Society.
PMID- 27508950
TI - Prenatally diagnosed fetal tumors of the head and neck: a systematic review with
antenatal and postnatal outcomes over the past 20 years.
AB - AIM: The aim of this study was to review prenatally diagnosed tumors of the head
and neck in the fetus and to report antenatal and postnatal outcomes. METHODS:
PubMed/Medline, EMBASE/SCOPUS, Cochrane database and Google Scholar were reviewed
over the last 20 years. No language or article type restriction was used.
RESULTS: A total of 1940 record were retrieved. Of the 713 records screened, 566
full-text articles were assessed for eligibility. After 445 articles were
excluded for specified reasons, 111 studies met the research criteria and were
included for qualitative analysis. Overall, 306 cases of fetal tumors of the head
and neck were reviewed. Maternal age was an independent factor. The mean maternal
age was 28.2 years and gestational age at prenatal diagnosis was 27.1 weeks.
Conventional 2D ultrasound was the standard diagnostic procedure in 27.9% of
cases and was implemented in 27.3% of cases by 3D ultrasound and fetal magnetic
resonance imaging (MRI). Diagnostic evaluation of intracranial spreading and high
airway obstructions was greatly enhanced by fetal MRI. The more common type of
fetal tumor was hemangioma/lymphangioms (42.1%), followed by teratomas (29.7%),
tumors of the gingiva (10.1%) and lymphatic venous malformations (9.1%),
respectively. Fetal karyotyping was performed only in 9.8% of cases; within
fetuses undergoing karyotype, chromosomal abnormalities accounted for 20% of
cases. The most common pregnancy complication was polyhydramnios (26.3%). Ex
utero intrapartum treatment (EXIT) procedure was performed in 30.1% of cases
while surgical excision was used in 22.9% during postnatal life. The survival
rate was 35.35%. CONCLUSION: Fetal tumors of the head and neck are rare
congenital malformations. Two-dimensional ultrasound is diagnostic in almost all
cases; however, MRI may be an important diagnostic adjunct in targeted cases and
help patient selection for immediate intubation at the time of delivery. EXIT
procedure and surgical removal of the tumor was associated with good prognosis.
PMID- 27508951
TI - Fourfold increase in prevalence of gestational diabetes mellitus after adoption
of the new International Association of Diabetes and Pregnancy Study Groups
(IADPSG) criteria.
AB - BACKGROUND: The aim was to evaluate the influence of the new International
Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines for
screening of gestational diabetes mellitus (GDM) on GDM prevalence in a cohort
from a Swiss tertiary hospital. METHODS: This was a retrospective cohort study
involving all pregnant women who were screened for GDM between 24 and 28 weeks of
gestation. From 2008 until 2010 (period 1), a two-step approach with 1-h 50 g
glucose challenge test (GCT) was used, followed by fasting, 1- and 2-h glucose
measurements after a 75 g oral glucose tolerance test (OGTT) in case of a
positive GCT. From 2010 until 2013 (period 2), all pregnant women were tested
with a one-step 75 g OGTT according to new IADPSG guidelines. In both periods,
women with risk factors could be screened directly with a 75 g OGTT in early
pregnancy. RESULTS: Overall, 647 women were eligible for the study in period 1
and 720 in period 2. The introduction of the IADPSG criteria resulted in an
absolute increase of GDM prevalence of 8.5% (3.3% in period 1 to 11.8% in period
2). CONCLUSIONS: The adoption of the IADPSG criteria resulted in a considerable
increase in GDM diagnosis in our Swiss cohort. Further studies are needed to
investigate if the screening is cost effective and if treatment of our
additionally diagnosed GDM mothers might improve short-term as well as long-term
outcome.
PMID- 27508952
TI - Depressive symptoms, hostility, and hopelessness in inner-city adolescent health
clinic patients: factor structure and demographic correlates.
AB - BACKGROUND: Depression, hostility, and hopelessness are risk factors for adult
cardiovascular disease (CVD). People living in inner-city environments are
particularly vulnerable. These associations may begin in adolescence, but
research in this area is hampered by inadequate knowledge about how these
negative psychological factors are related in teens and how they are affected by
demographic characteristics. We hypothesized that depression, hostility, and
hopelessness are one construct, and that this construct would be associated with
race and gender in attendees at an inner-city adolescent health clinic. METHODS:
Two hundred and forty-six 15-18-year-old patients filled out instruments
measuring depressive symptoms, hostility, and hopelessness. Confirmatory factor
analysis was used to determine whether the negative psychological factors
comprised a single construct or three separate ones. General linear modeling
(GLM) was used to test the associations between demographic characteristics and
the results of the factor analysis. RESULTS: Depressive symptoms, hostility, and
hopelessness were best characterized as three separate constructs, not one (root
mean square error of approximation (RMSEA)=0.041, 90% confidence interval
(CI)=(0.035, 0.047), comparative fit index (CFI)=0.98). There were no significant
relationships between demographic variables and depressive symptoms or hostility.
Six percent of the variance in hopelessness scores was accounted for by gender,
race, and the interaction between the two (F=3.76; p=0.006), with White males,
reporting the highest levels of hopelessness. CONCLUSION: In an urban adolescent
health clinic population, depressive symptoms, hostility, and hopelessness were
best understood as three separate constructs. Hopelessness was significantly
higher in White males. Implications for future clinical research on negative
psychological factors in teens are discussed.
PMID- 27508953
TI - Evaluation of social anxiety, self-esteem, life quality in adolescents with acne
vulgaris.
AB - BACKGROUND: Acne vulgaris is a visible skin disease commonly seen in adolescence.
As it affects the appearance, it is likely to bring stress to the adolescent's
life regarding sensitivity about their appearance. OBJECTIVE: The aim of the
study was to investigate the social anxiety level, acne-specific life quality,
and self-esteem among adolescents with acne vulgaris. In addition, we evaluated
the relationship between these parameters, clinical severity, and
sociodemographic data. METHODS: One hundred and two adolescents with acne
vulgaris, aged 12-17 years without any psychiatric or medical comorbidity were
recruited. The control group consisted of 83 adolescents in the same age range,
who had neither psychiatric disease nor acne. Sociodemographic form (SDF), Capa
Social Phobia Scale for Children and Adolescents (CSPSCA), and Rosenberg Self
esteem Scale (RSES) were applied to both groups. Additionally, the severity of
acne was determined with Global Acne Grading System (GAGS), and life quality of
the patients was evaluated with Acne Quality of Life Scale (AQOL). RESULTS: There
was no significant difference in social anxiety levels and self-esteem between
the study and control groups. Life quality impairment and high social anxiety
levels, as well as low self-esteem, were found to be associated regardless of the
clinical severity. CONCLUSION: Clinicians should be aware of the psychiatric
comorbidities when treating adolescents with acne vulgaris. Especially, low self
esteem and life quality impairment should warn clinicians to predict high social
anxiety levels in adolescent acne patients.
PMID- 27508954
TI - Immune status of representative infectious diseases among Japanese female
university students.
AB - OBJECTIVE: To elucidate the immune status of representative infectious diseases
among Japanese youth, we retrospectively investigated serum antibody levels in
university students, partly comparing these to immunization records and
infectious disease histories confirmed by the maternal and child health (MCH)
handbooks. MATERIALS AND METHODS: In total, 168 Japanese female university
students, aged 20-21 years, were included. Data were collected from examinations
of antibody titers against measles, rubella, varicella-zoster (VZ), mumps, and
hepatitis B (HB) and C (HC) viruses, and from QuantiFERON(r)-TB Gold tests,
between 2011 and 2015. Records of immunization and infectious disease histories
were available from MCH handbooks for students who agreed with the use of their
data for this study (n=23). RESULTS: All students had positive antibodies,
detected by enzyme immunoassay (EIA), against measles, rubella, VZ, and mumps;
however, seroprevalences within the range of seroprotective antibody levels were
38.1% (64/168), 67.9% (114/168), 95.9% (141/147), and 89.8% (132/147),
respectively. The students had probably not been infected with HB, HC, or
tuberculosis at the time of the examinations. DISCUSSION: The study indicated
that a two-dose vaccine for measles and rubella (MR) might not be sufficient to
produce antibodies at seroprotective levels. Therefore, we propose that health
care workers, including students, should receive an additional MR vaccine, even
if they have received two doses of MR vaccine or if they have unknown histories
of immunizations or infectious diseases. Further investigations in these areas
will be needed.
PMID- 27508955
TI - From oliguria to urinary incontinence: a case of Munchausen's syndrome in an
adolescent boy.
AB - Factitious disorders are characterized by physical or psychological symptoms that
are intentionally produced or feigned in order to assume the sick role.
"Munchausen's syndrome" is one of these disorders and often is under-recognized
or only suspected after unnecessary investigations. We report the case of a 15
year-old boy who came to our notice because of reduced urine output and recurrent
abdominal pain during the previous 3 months. The patient attended several
emergency room visits and he had been hospitalized for 1 month in an adult
internal medicine department because of "oliguria". He had undergone several
invasive investigations with normal results before the diagnosis of Munchausen's
syndrome was made. General pediatricians and practitioners should be aware that
suspecting Munchausen's syndrome in the first instance in the management of a
patient showing discrepancies between reported urinary symptoms and the
detectable clinical signs could avoid unnecessary and invasive exams.
PMID- 27508956
TI - Eating habits and presence of cardiovascular risks in children.
AB - INTRODUCTION: The changes in the eating habits associated with physical
inactivity are directly related to the increase in the prevalence of obesity and
associated diseases such as diabetes mellitus (DM), metabolic syndrome and
cardiovascular diseases. OBJECTIVE: The aim of this study was to investigate the
relationship between the frequency of consumption of some food groups (snacks,
fruits, vegetables and candies), physical exercise, nutritional classification
and biochemical profile in children. METHODS: After the approval of the Ethics
Committee, we studied 882 schoolchildren ranging between 6 and 10 years of age.
Biochemical and anthropometric evaluations were performed and questionnaires were
used in order to check the eating habits and physical activity. RESULTS: Our
results showed that we may relate the consumption of snacks, fruits, vegetables
or candies with modifications in the glycemia, triglycerides, total cholesterol,
HDL-c, and LDL-c but we did not observe association with the nutritional
classification. It is noteworthy to say that almost 50% of the studied children
were overweight or obese and many presented alterations in the lipid and glucose
levels. CONCLUSION: Our results also show that many children have abnormal levels
of lipids and glycemia and a great number of them are classified as overweight or
obese. In this context, we can say that urgent approaches are needed to be
carried out by a multidisciplinary team in order to improve the diet and reduces
the risk factors in this population of children and prevent secondary diseases in
adolescence and adulthood.
PMID- 27508957
TI - Prevalence and risk factors associated with suicidal ideation among adolescents
in Malaysia.
AB - BACKGROUND: Suicidal ideation, defined as thoughts, ideas and the desire to
commit suicide, is becoming a major public health problem among adolescents.
Indeed, suicidal ideation is known as a key predictor of future suicide risk.
OBJECTIVE: This study aims to determine the prevalence and risk factors
associated with suicidal ideation among adolescents in Malaysia. METHODS: This
study used data from the 2013 Malaysian adolescent health risk behavior (MyAHRB)
study, a cross-sectional school survey conducted in Peninsular Malaysia among
school-going adolescents aged 16-17 years (n=2789). Logistic regression analysis
was used to determine the risk factors associated with suicidal ideation among
Malaysian adolescents. RESULTS: The overall prevalence of suicidal ideation among
the adolescents was 6.2%. The prevalence was significantly higher among females
than males (7.6% vs. 4.7%; p=0.002). Multivariate regression analysis revealed
that adolescents who were females [odds ratio (OR)=2.02; 95% confidence interval
(CI): 1.40-2.92] or of Indian ethnicity (OR=2.32; 95% CI: 1.35-3.98) were more
likely to report suicidal ideation. Loneliness (OR=2.54; 95% CI: 1.57-4.11),
anxiety or worry (OR=2.70; 95% CI: 1.70-4.31), no close friends (OR=2.71; 95% CI:
1.43-5.14), and lack of supportive peers (OR=1.69; 95% CI: 1.15-2.47) were
identified as risk factors for adolescents' suicidal ideation. Adolescents who
ever had sexual intercourse (OR=2.70; 95% CI: 1.48-4.92) and had been in a
physical fight (OR=2.45; 95% CI: 1.62-3.70) were also reported to have higher
risks of suicidal ideation. CONCLUSION: This study provides evidence on risk
factors associated with suicidal ideation among Malaysian adolescents. Targeted
mental health and health risk behavioral interventions for high-risk adolescents
are recommended.
PMID- 27508958
TI - Who is teaching the kids to cook? Results from a nationally representative survey
of secondary school students in New Zealand.
AB - Learning how to cook is an important skill for developing healthy eating
behaviors. Moreover, involvement in home cooking may offer young people
opportunities for skill building, identity development and social engagement with
their families. Recently, there have been concerns that the current generation of
young people may not have the opportunities to develop sufficient cooking skills.
These concerns have been addressed by the initiation of numerous, localized
interventions. Yet, little is known about where the current generation of young
people learn cooking skills. The objective of this study was to describe where
the current generation of young people report learning to cook, drawing on
nationally representative data from New Zealand. Data were collected as part of
Youth2012, a nationally representative survey of secondary school students
(n=8500) in New Zealand. Almost all students reported learning to cook and from
multiple sources. Almost all students reported learning to cook from a family
member (mother, father, or other family member), approximately 60% of students
reported that they learned to cook from certain media (cookbooks, TV, or the
Internet) and half of all students reported learning to cook at school. There
were numerous differences in where students learned to cook by socio-demographic
characteristics. Findings from the current research highlight the important role
that families play in teaching young people to cook and will be useful for those
working with young people to develop these skills.
PMID- 27508959
TI - Brain-derived neurotrophic factor: a mediator of inflammation-associated
neurogenesis in Alzheimer's disease.
AB - In early- or late-onset Alzheimer's disease (AD), inflammation, which is
triggered by pathologic conditions, influences the progression of
neurodegeneration. Brain-derived neurotrophic factor (BDNF) has emerged as a
crucial mediator of neurogenesis, because it exhibits a remarkable activity
dependent regulation of expression, which suggests that it may link inflammation
to neurogenesis. Emerging evidence suggests that acute and chronic inflammation
in AD differentially modulates neurotrophin functions, which are related to the
roles of inflammation in neuroprotection and neurodegeneration. Recent studies
also indicate novel mechanisms of BDNF-mediated neuroprotection, including the
modulation of autophagy. Numerous research studies have demonstrated reverse
parallel alterations between proinflammatory cytokines and BDNF during
neurodegeneration; thus, we hypothesize that one mechanism that underlies the
negative impact of chronic inflammation on neurogenesis is the reduction of BDNF
production and function by proinflammatory cytokines.
PMID- 27508960
TI - Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression
like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression
in mice.
AB - BACKGROUND: The inflammatory response system has been implicated in the
pathophysiology of major depression. The pro-inflammatory cytokines like
interferon-gamma induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the
kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the
availability of tryptophan for serotonin synthesis. Furthermore, the metabolites
of kynurenine pathway have neurotoxic property, which along with decreased
serotonin may account for depression-like illness. METHODS: The aim of this study
was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan
(1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression
in mice. Behavioral tests included locomotor activity, forced swim test (FST) and
tail suspension test (TST). Oxidative stress was assessed by examining the levels
of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in
homogenized whole brain samples. Comet assays were performed to assess
neurotoxicity. RESULTS: The results of this study demonstrate that BCG treatment
resulted in an increase in duration of immobility in FST and TST as compared to
the saline group. Further, it produced a significant increase in the brain TBARS
levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG
group had significantly more comet cells than the saline group. 1-MT and
fluoxetine were able to reverse the BCG-induced depression-like behavior and the
derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the
BCG-induced neurotoxicity in such mice. CONCLUSIONS: 1-Methyl-L-tryptophan
exhibits antidepressant-like effect comparable to that of fluoxetine in treating
BCG-induced depression-like behavior in mice.
PMID- 27508961
TI - Anti-acetylcholinesterase activity of essential oils and their major constituents
from four Ocimum species.
AB - Ocimum is a genus of considerable importance in traditional medicine worldwide.
The goal of this study was to examine the anti-acetylcholinesterase activity of
Ocimum essential oils and to correlate the activity with their chemical profiles
using a metabolome based GC-MS approach coupled to chemometrics. Further,
molecular docking was adopted to rationalize the activity of some essential oil
isolates. Essential oil prepared from the four species O. basilicum, O.
africanum, O. americanum, and O. minimum exhibited significant anti
acetylcholinesterase activity with (IC50 0.22, 0.175, 0.57 and 0.152 mg/mL,
respectively) comparable to that of physostigmine (IC50 0.27 mg/mL). The
phenylpropanoids (i.e. estragole) constituted the most dominant chemical group in
O. basilicum (sweet basil) and O. minimum, whereas camphor (a ketone) was the
most abundant in O. africanum and O. americanum. Supervised and unsupervised
multivariate data analyses clearly separated O. africanum and O. americanum from
other accessions, with estragole, camphor and, to less extent, beta-linalool
contributing to species segregation. Estragole was found the most active AchE
inhibitor (IC50 0.337 uM) followed by cineole (IC50 2.27 uM), camphor (IC50 21.43
uM) and eugenol (IC50 40.32 uM). Molecular docking revealed that these compounds
bind to key amino acids in the catalytic domain of AchE, similar to standard
drugs.
PMID- 27508962
TI - Alpha-synuclein at the intracellular and the extracellular side: functional and
dysfunctional implications.
AB - Alpha-synuclein (alpha-syn) is an abundant neuronal protein whose physiological
function, even if still not completely understood, has been consistently related
to synaptic function and vesicle trafficking. A group of disorders known as
synucleinopathies, among which Parkinson's disease (PD), is deeply associated
with the misfolding and aggregation of alpha-syn, which can give rise to
proteinaceous inclusion known as Lewy bodies (LB). Proteostasis stress is a
relevant aspect in these diseases and, currently, the presence of oligomeric
alpha-syn species rather than insoluble aggregated forms, appeared to be
associated with cytotoxicity. Many observations suggest that alpha-syn is
responsible for neurodegeneration by interfering with multiple signaling
pathways. alpha-syn protein can directly form plasma membrane channels or modify
with their activity, thus altering membrane permeability to ions, abnormally
associate with mitochondria and cause mitochondrial dysfunction (i.e.
mitochondrial depolarization, Ca2+ dys-homeostasis, cytochrome c release) and
interfere with autophagy regulation. The picture is further complicated by the
fact that single point mutations, duplications and triplication in alpha-syn gene
are linked to autosomal dominant forms of PD. In this review we discuss the multi
faced aspect of alpha-syn biology and address the main hypothesis at the basis of
its involvement in neuronal degeneration.
PMID- 27508963
TI - E-beam crosslinked nanogels conjugated with monoclonal antibodies in targeting
strategies.
AB - Poly(N-vinyl pyrrolidone)-based-nanogels (NGs), produced by e-beam irradiation,
are conjugated with monoclonal antibodies (mAb) for active targeting purposes.
The uptake of immuno-functionalized nanogels is tested in an endothelial cell
line, ECV304, using confocal and epifluorescence microscopy. Intracellular
localization studies reveal a faster uptake of the immuno-nanogel conjugate with
respect to the 'bare' nanogel. The specific internalization pathway of these
immuno-nanogels is clarified by selective endocytosis inhibition experiments,
flow cytometry and confocal microscopy. Active targeting ability is also verified
by conjugating a monoclonal antibody which recognizes the alphavbeta3 integrin on
activated endothelial cells. Epifluorescence images of the 'wound healing assay'
on ECV304 cells provide evidence of nanogels localization only in the target
cells. Therefore, the immuno-nanogels produced have the potential to recognize
specific cell types in heterogeneous systems, which makes them promising
candidates for targeted drug delivery applications.
PMID- 27508964
TI - Pituitary-bone connection in skeletal regulation.
AB - Pituitary hormones have traditionally been thought to exert specific, but limited
function on target tissues. More recently, the discovery of these hormones and
their receptors in organs such as the skeleton suggests that pituitary hormones
have more ubiquitous functions. Here, we discuss the interaction of growth
hormone (GH), follicle stimulating hormone (FSH), thyroid stimulating hormone
(TSH), adrenocorticotrophic hormone (ACTH), prolactin, oxytocin and arginine
vasopressin (AVP) with bone. The direct skeletal action of pituitary hormones
therefore provides new insights and therapeutic opportunities for metabolic bone
diseases, prominently osteoporosis.
PMID- 27508966
TI - The self-perception of dyspnoea threshold during the 6-min walk test: a good
alternative to estimate the ventilatory threshold in chronic obstructive
pulmonary disease.
AB - To determine and/or adjust exercise training intensity for patients when the
cardiopulmonary exercise test is not accessible, the determination of dyspnoea
threshold (defined as the onset of self-perceived breathing discomfort) during
the 6-min walk test (6MWT) could be a good alternative. The aim of this study was
to evaluate the feasibility and reproducibility of self-perceived dyspnoea
threshold and to determine whether a useful equation to estimate ventilatory
threshold from self-perceived dyspnoea threshold could be derived. A total of 82
patients were included and performed two 6MWTs, during which they raised a hand
to signal self-perceived dyspnoea threshold. The reproducibility in terms of
heart rate (HR) was analysed. On a subsample of patients (n=27), a stepwise
regression analysis was carried out to obtain a predictive equation of HR at
ventilatory threshold measured during a cardiopulmonary exercise test estimated
from HR at self-perceived dyspnoea threshold, age and forced expiratory volume in
1 s. Overall, 80% of patients could identify self-perceived dyspnoea threshold
during the 6MWT. Self-perceived dyspnoea threshold was reproducibly expressed in
HR (coefficient of variation=2.8%). A stepwise regression analysis enabled
estimation of HR at ventilatory threshold from HR at self-perceived dyspnoea
threshold, age and forced expiratory volume in 1 s (adjusted r=0.79, r=0.63, and
relative standard deviation=9.8 bpm). This study shows that a majority of
patients with chronic obstructive pulmonary disease can identify a self-perceived
dyspnoea threshold during the 6MWT. This HR at the dyspnoea threshold is highly
reproducible and enable estimation of the HR at the ventilatory threshold.
PMID- 27508967
TI - Interlimb weight adjustments between the lower and upper limbs relate to
inaccurate performance during the lateral body weight-shifting task.
AB - The lateral body weight-shifting task is commonly used in therapeutic programs
for patients with orthopedic complaints or hemiparesis. Although the patients
usually support themselves using the upper limbs during the task, it is unclear
whether the use of upper limbs affects performance accuracy of lateral body
weight shifting. Therefore, the aim of this study was to investigate the effects
of support by the upper limbs on performance accuracy, particularly on the
central tendency effects (i.e. overshooting for light targets and undershooting
for heavy targets). Twenty-three able-bodied, neurologically intact individuals,
who were right-handed and right-footed participants performed the lateral body
weight-shifting task to shift one-third or two-thirds of their body weight toward
the left and right lower limbs using support by the upper limbs. The result of
correlation coefficients between interlimb weight adjustment and errors showed
that the use of the upper limbs and interlimb weight adjustment related to the
enhanced central tendency effects. The use of upper limbs generally contributes
toward stabilizing posture, however, this is not the case with performance of the
lateral body weight shifting. Moreover, the effects of using the upper limb on
performance accuracy differed among leftward and rightward weight shifting. This
result might be owing to the dominant side of the hand/foot and hemisphere
lateralization.
PMID- 27508965
TI - Accumbal MU-Opioid Receptors Modulate Ethanol Intake in Alcohol-Preferring Alko
Alcohol Rats.
AB - BACKGROUND: The nucleus accumbens shell is a key brain area mediating the
reinforcing effects of ethanol (EtOH). Previously, it has been shown that the
density of MU-opioid receptors in the nucleus accumbens shell is higher in
alcohol-preferring Alko Alcohol (AA) rats than in alcohol-avoiding Alko Non
Alcohol rats. In addition, EtOH releases opioid peptides in the nucleus accumbens
and opioid receptor antagonists are able to modify EtOH intake, all suggesting an
opioidergic mechanism in the control of EtOH consumption. As the exact mechanisms
of opioidergic involvement remains to be elucidated, the aim of this study was to
clarify the role of accumbal MU- and kappa-opioid receptors in controlling EtOH
intake in alcohol-preferring AA rats. METHODS: Microinfusions of the MU-opioid
receptor antagonist CTOP (0.3 and 1 MUg/site), MU-opioid receptor agonist DAMGO
(0.03 and 0.1 MUg/site), nonselective opioid receptor agonist morphine (30
MUg/site), and kappa-opioid receptor agonist U50488H (0.3 and 1 MUg/site) were
administered via bilateral guide cannulas into the nucleus accumbens shell of AA
rats that voluntarily consumed 10% EtOH solution in an intermittent, time
restricted (90-minute) 2-bottle choice access paradigm. RESULTS: CTOP (1
MUg/site) significantly increased EtOH intake. Conversely, DAMGO resulted in a
decreasing trend in EtOH intake. Neither morphine nor U50488H had any effect on
EtOH intake in the used paradigm. CONCLUSIONS: The results provide further
evidence for the role of accumbens shell MU-opioid receptors but not kappa-opioid
receptors in mediating reinforcing effects of EtOH and in regulating EtOH
consumption. The results also provide support for views suggesting that the
nucleus accumbens shell has a major role in mediating EtOH reward.
PMID- 27508968
TI - The use of commercial video games in rehabilitation: a systematic review.
AB - The aim of this paper was to investigate the effect of commercial video games
(VGs) in physical rehabilitation of motor functions. Several databases were
screened (Medline, SAGE Journals Online, and ScienceDirect) using combinations of
the following free-text terms: commercial games, video games, exergames, serious
gaming, rehabilitation games, PlayStation, Nintendo, Wii, Wii Fit, Xbox, and
Kinect. The search was limited to peer-reviewed English journals. The beginning
of the search time frame was not restricted and the end of the search time frame
was 31 December 2015. Only randomized controlled trial, cohort, and observational
studies evaluating the effect of VGs on physical rehabilitation were included in
the review. A total of 4728 abstracts were screened, 275 were fully reviewed, and
126 papers were eventually included. The following information was extracted from
the selected studies: device type, number and type of patients, intervention, and
main outcomes. The integration of VGs into physical rehabilitation has been
tested for various pathological conditions, including stroke, cerebral palsy,
Parkinson's disease, balance training, weight loss, and aging. There was large
variability in the protocols used (e.g. number of sessions, intervention
duration, outcome measures, and sample size). The results of this review show
that in most cases, the introduction of VG training in physical rehabilitation
offered similar results as conventional therapy. Therefore, VGs could be added as
an adjunct treatment in rehabilitation for various pathologies to stimulate
patient motivation. VGs could also be used at home to maintain rehabilitation
benefits.
PMID- 27508969
TI - Chitosan crosslinked flat scaffolds for peripheral nerve regeneration.
AB - Chitosan (CS) has been widely used in a variety of biomedical applications,
including peripheral nerve repair, due to its excellent biocompatibility,
biodegradability, readily availability and antibacterial activity. In this study,
CS flat membranes, crosslinked with dibasic sodium phosphate (DSP) alone (CS/DSP)
or in association with the gamma-glycidoxypropyltrimethoxysilane (CS/GPTMS_DSP),
were fabricated with a solvent casting technique. The constituent ratio of
crosslinking agents and CS were previously selected to obtain a composite
material having both adequate mechanical properties and high biocompatibility. In
vitro cytotoxicity tests showed that both CS membranes allowed cell survival and
proliferation. Moreover, CS/GPTMS_DSP membranes promoted cell adhesion, induced
Schwann cell-like morphology and supported neurite outgrowth from dorsal root
ganglia explants. Preliminary in vivo tests carried out on both types of nerve
scaffolds (CS/DSP and CS/GPTMS_DSP membranes) demonstrated their potential for:
(i) protecting, as a membrane, the site of nerve crush or repair by end-to-end
surgery and avoiding post-operative nerve adhesion; (ii) bridging, as a conduit,
the two nerve stumps after a severe peripheral nerve lesion with substance loss.
A 1 cm gap on rat median nerve was repaired using CS/DSP and CS/GPTMS_DSP
conduits to further investigate their ability to induce nerve regeneration in
vivo. CS/GPTMS_DSP tubes resulted to be more fragile during suturing and, along a
12 week post-operative lapse of time, they detached from the distal nerve stump.
On the contrary CS/DSP conduits promoted nerve fiber regeneration and functional
recovery, leading to an outcome comparable to median nerve repaired by autograft.
PMID- 27508970
TI - Development and validation of a multiresidue method for the analysis of more than
500 pesticides and drugs in water based on on-line and liquid chromatography
coupled to high resolution mass spectrometry.
AB - Screening of a large number of emerging pollutants is highly desirable for the
control of water quality. In this respect, a novel, fully automated contaminant
screening method based on an integrated sample preconcentration and liquid
chromatography coupled to high resolution mass spectrometry (SPE-UHPLC-HRMS) has
been developed. The optimal chromatographic column and experimental conditions
allowing the retention and subsequent elution of the maximum number of analytes
were defined. Liquid chromatography and Q-exactive (OrbitrapTM) parameters were
optimized to obtain the best separation of molecules of interest, and the lowest
detection limits. Due to the large amount of data to compare, a script written in
R language was developed to evaluate the quality of the data generated by the
comparison of 14 experimental conditions. The developed method enables the
simultaneous semi quantitative analysis of 539 compounds (pesticides and drug
residues), in 36 min with only 5 mL of water. Method validation was achieved
through studies of repeatability, selectivity, linearity and matrix effect.
Application to 20 tap water samples collected in and around Paris showed the
presence of 34 different compounds all with concentrations below 0.1 MUg/L, the
European Union limit for drinking water. Pesticides and transformation products
frequently found in water resources such as atrazine and its metabolites,
hexazinone, oxadixyl, propazine and simazine were detected. Drug residues such as
valsartan and carbamazepine, usually not monitored, were also found. The next
step will be to assess the ability of this method to highlight the presence of
unexpected contaminants not present in our database.
PMID- 27508971
TI - Characterization of the relationship between ceramic pot filter water production
and turbidity in source water.
AB - Ceramic pot filters represent a common and effective household water treatment
technology in developing countries, but factors impacting water production rate
are not well-known. Turbidity of source water may be principal indicator in
characterizing the filter's lifetime in terms of water production capacity. A
flow rate study was conducted by creating four controlled scenarios with
different turbidities, and influent and effluent water samples were tested for
total suspended solids and particle size distribution. A relationship between
average flow rate and turbidity was identified with a negative linear trend of 50
mLh-1/NTU. Also, a positive linear relationship was found between the initial
flow rate of the filters and average flow rate calculated over the 23 day life of
the experiment. Therefore, it was possible to establish a method to estimate the
average flow rate given the initial flow rate and the turbidity in the influent
water source, and to back calculate the maximum average turbidity that would need
to be maintained in order to achieve a specific average flow rate. However, long
term investigations should be conducted to assess how these relationships change
over the expected CPF lifetime. CPFs rejected fine suspended particles (below 75
MUm), especially particles with diameters between 0.375 MUm and 10 MUm. The
results confirmed that ceramic pot filters are able to effectively reduce
turbidity, but pretreatment of influent water should be performed to avoid
premature failure.
PMID- 27508972
TI - Experimental and theoretical insights into the photochemical decomposition of
environmentally persistent perfluorocarboxylic acids.
AB - Decomposition of perfluorocarboxylic acids (PFCAs) is of great significance due
to their global distribution, persistence and toxicity to organisms. In this
study, the photodegradation of a series of PFCAs (~C2C12) in water by a medium
pressure mercury lamp was experimentally and theoretically examined. We found
that photolysis of PFCAs all follow pseudo-first-order kinetics with the rate
constant (kapp) increasing with carbon chain lengths, except for trifluoroacetic
acid (TFA) which cannot be degraded by the polychromatic irradiation. Product
analysis showed that the PFCAs were mainly decomposed into shorter carbon chain
length PFCAs in a stepwise manner, with the accumulation of TFA and fluoride ions
as the end products. Moreover, a small amount of perfluoroolefins (CnF2n) was
determined as gas-phase products. Wiberg bond order calculations confirmed the
cleavage of the CC bond between carboxylic carbon and the adjacent carbon as the
first reaction step, and density functional theory-based calculations revealed
that kapp value is correlated with some molecular structural parameters. In the
case of mixture irradiation, the evolution profiles of individual PFCAs were
different from that in single-component systems, due to the dynamic balance
between production and degradation. This work reveals the main molecular
descriptors controlling the degradation rate of different PFCAs species, and
improves the general understanding on the photodegradation mechanisms, which will
provide useful information for future researches.
PMID- 27508973
TI - Generation of dissolved organic matter and byproducts from activated sludge
during contact with sodium hypochlorite and its implications to on-line chemical
cleaning in MBR.
AB - On-line chemical cleaning of membranes with sodium hypochlorite (NaClO) has been
commonly employed for maintaining a constant permeability of membrane bioreactor
(MBR) due to its simple and efficient operation. However, activated sludge is
inevitably exposed to NaClO during this cleaning process. In spite of the broad
applications of on-line chemical cleaning in MBR such as chemical cleaning-in
place (CIP) and chemical enhanced backwash (CEB), little information is currently
available for the release of emerging dissolved organic matter (DOM) and
byproducts from this prevalent practice. Therefore, in this study, activated
sludge suspended in a phosphate buffered saline solution was exposed to different
doses of NaClO in order to determine the generation of potential DOM and
byproducts. The results showed the occurrence of significant DOM release (up to
24.7 mg/L as dissolved organic carbon) after exposure to NaClO for 30 min. The
dominant components of the released DOM were characterized to be humic acid-like
as well as protein-like substances by using an excitation-emission matrix
fluorescence spectrophotometer. Furthermore, after the contact of activated
sludge with NaClO, 19 kinds of chlorinated and brominated byproducts were
identified by ultra performance liquid chromatography/electrospray ionization
triple quadrupole mass spectrometry, eight of which were confirmed and
characterized with standard compounds. Many byproducts were found to be
halogenated aromatic compounds, including halopyrroles and
halo(hydro)benzoquinones, which had been reported to be significantly more toxic
than the halogenated aliphatic ones. Consequently, this study offers new insights
into the practice of on-line chemical cleaning, and opens up a window to re
examine the current operation of MBR by looking into the generation of
micropollutants.
PMID- 27508974
TI - Thermal hydrolysis for sewage treatment: A critical review.
AB - A review concerning the development and applicability of sewage sludge thermal
hydrolysis especially prior to anaerobic digestion is presented. Thermal
hydrolysis has proven to be a successful approach to making sewage sludge more
amenable to anaerobic digestion. Currently there are 75 facilities either in
operation or planning, spanning several continents with the first installation in
1995. The reported benefits of thermal hydrolysis relate to: increased digestion
loading rate due to altered rheological properties, improved biodegradation of
(especially activated) sludge and enhanced dewaterability. In spite of its
relative maturity, there has been no attempt to perform a critical review of the
pertinent literature relating to the technology. Closer look at the literature
reveals complications with comparing both experimental- and full-scale results
due to differences in experimental set-up and capability, and also site-specific
conditions at full-scale. Furthermore, it appears that understanding of
thermodynamic and rheological properties of sludge is key to optimizing the
process, however these parameters are largely overlooked by the literature. This
paper aims to bridge these complexities in order to elucidate the benefits of
thermal hydrolysis for sewage treatment, and makes recommendations for further
development and research.
PMID- 27508976
TI - MDM2 and CDK4 Immunohistochemistry: Should It Be Used in Problematic
Differentiated Lipomatous Tumors?: A New Perspective.
AB - Although most cases of atypical lipomatous tumor/well-differentiated liposarcoma
(ALT/WDL) can be diagnosed solely on the basis of histologic features, those
lacking diagnostic histologic features require ancillary studies for accurate
classification. Fluorescent in situ hybridization (FISH) for amplification of
MDM2 has been considered the gold standard for diagnosis in these situations.
Immunostaining for MDM2 and/or CDK4 has been adopted as a surrogate method
because of its high concordance rate with FISH and lower cost. However, studies
examining the concordance of the 2 methods have been based preferentially on
cases in which the diagnosis could be established histologically. No study has
explored the concordance between the 2 methods in histologically ambiguous cases
or in cases in which the diagnosis of ALT/WDL is not apparent after a review of
all slides. To address this, we performed immunostaining for MDM2 and CDK4 on 183
well-differentiated lipomatous tumors that could not be diagnosed on purely
histologic grounds and that were, therefore, subjected to FISH analysis. These
included ALT/WDLs (n=56), lipomas (n=96), and lipoma variants (n=31). Staining
for MDM2 and CDK4 was noted in 25/56 and 23/56 ALT/WDL, respectively, giving a
sensitivity of 45% and 41% and a specificity of 98% and 92%. Staining was noted
exclusively in the nuclei of atypical cells and not in the nuclei of adipocytes.
Staining for MDM2 and CDK4 occurred in 2/125 and 10/117 benign lipomatous
lesions, respectively. False-positive staining was equivalent in intensity to
ALT/WDL. We conclude that MDM2 and CDK4 staining is a relatively insensitive
method for diagnosing ALT/WDL in cases that are histologically ambiguous, as
staining is restricted to neoplastic cells with atypia that are underrepresented
in these cases. Therefore, in cases like ours that closely simulate clinical
practice, FISH is the more reliable and cost-effective option.
PMID- 27508975
TI - Undifferentiated Carcinoma With Osteoclastic Giant Cells of the Pancreas:
Clinicopathologic Analysis of 38 Cases Highlights a More Protracted Clinical
Course Than Currently Appreciated.
AB - Undifferentiated carcinomas with osteoclastic giant cells of the pancreas (OGC)
are rare tumors. The current impression in the literature is that they are highly
aggressive tumors similar in prognosis to ductal adenocarcinomas. In this study,
the clinicopathologic characteristics of 38 resected OGCs were investigated and
contrasted with 725 resected pancreatic ductal adenocarcinomas without
osteoclastic cells (PDCs). The frequency among systematically reviewed pancreatic
cancers was 1.4%. OGCs showed a slight female predominance (62.9%, vs. 51.4% in
PDCs). The mean age was 57.9 years (vs. 65.0). The mean size of invasive cancer
was 5.3 cm (vs. 3.2). They were characterized by nodular, pushing-border growth,
and 8 arose in tumoral intraepithelial neoplasms (4 in mucinous cystic neoplasms,
4 in intraductal papillary mucinous neoplasms type lesions), and 23 (61%) also
showed prominent intraductal/intracystic growth. Twenty-nine (76%) had an
invasive ductal/tubular adenocarcinoma component. Osteoid was seen in 12. Despite
their larger size, perineural invasion and nodal metastasis were uncommon (31.6%
and 22.6%, vs. 85.5% and 64.0%, respectively). Immunohistochemistry performed on
24 cases revealed that osteoclastic cells expressed the histiocytic marker CD68,
and background spindle cells and pleomorphic/giant carcinoma cells often showed
p53 and often lacked cytokeratin. Survival of OGCs was significantly better than
that of PDCs (5 yr, 59.1% vs. 15.7%, respectively, P=0.0009). In conclusion,
pancreatic OGCs present with larger tumor size and in slightly younger patients
than PDC, 21% arise in mucinous cystic neoplasms/intraductal papillary mucinous
neoplasms, and 61% show intraductal/intracystic polypoid growth. OGCs have a
significantly better prognosis than is currently believed in the literature.
PMID- 27508977
TI - Abnormal blink reflex recovery cycle in manifesting and nonmanifesting carriers
of the DYT1 gene mutation.
AB - The aim of this study is to evaluate the brainstem function in DYT1 carriers
manifesting clinical dystonia (MDYT1) and those without clinical symptoms
(NMDYT1). Motor cortical inhibition and plasticity were found to be abnormal in
MDYT1, whereas these were less abnormal in NMDYT1. However, the spinal reciprocal
inhibition was abnormal in MDYT1, but normal in NMDYT1. Moreover, protein
accumulation and perinuclear inclusion bodies were found in the brainstem, but
not in other brain areas, in DYT1 patients. Therefore, we designed this study to
investigate the brainstem physiology using the blink reflex (BR) recovery cycle
test in MDYT1 and NMDYT1. We recruited eight MDYT1, five NMDYT1, and nine age
matched healthy controls. The BR recovery cycle was assessed with paired stimuli
that induced the BR in a random order at interstimulus intervals of 250, 500, and
1000 ms. A two-way analysis of variance showed a significant difference between
MDYT1, NMDYT1, and the healthy control (P=0.004). Post-hoc analysis showed that
this was because of a significantly lower inhibition of R2 in MDYT1 and NMDYT1
compared with the controls (two-way analysis of variance: P=0.003 and 0.021,
respectively). There was no difference between MDYT1 and NMDYT1 (P=0.224). The
tested brainstem circuits were equally involved in MDYT1 and NMDYT1. The finding
is in agreement with the pathological findings in DYT1 carriers. Together with
previous findings in the motor cortex and the spinal cord, the brainstem may lie
closer to the pathogenesis of dystonia than the motor cortex in DYT1 gene
carriers.
PMID- 27508978
TI - Genetic effects of XRCC4 and ligase IV genes on human glioma.
AB - Ligase IV and XRCC4 genes, important molecules in the nonhomologous end-joining
pathway for repairing DNA double-strand breaks, may play crucial roles in
carcinogenesis. To detect their effects on the risk of human glioma, their gene
expression differences between 110 human glioma tissues and 50 healthy brain
tissues were determined using quantitative real-time PCR. Furthermore, two
tagging single nucleotide polymorphisms (SNPs) in ligase IV and four SNPs in
XRCC4 genes were genotyped in 317 glioma patients and 352 healthy controls. The
association of glioma and ligase IV/XRCC4 was evaluated using methods for SNP,
haplotype, and gene-gene interaction analysis. Compared with those in normal
brain tissues, the relative gene expression levels of ligase IV and XRCC4 were
significantly downregulated in glioma tissue (P=0.0017 and 0.0006, respectively).
Single SNP analysis indicated that only rs10131 in ligase IV remained
significantly associated with glioma (P=0.0036) after 10 000 permutation tests.
Haplotype analysis showed that the haplotype profiles of ligase IV and XRCC4 were
significantly different between glioma patients and healthy controls (P=0.004 and
3.13E-6, respectively). Finally, the gene-gene interaction analysis suggested
that the three-locus model (rs1805388, rs10131, and rs2075685) was the best model
for ligase IV and XRCC4 to have interaction effects on the risk of glioma. In
conclusion, both ligase IV and XRCC4 may act in concert to modulate the
development of glioma.
PMID- 27508979
TI - State-dependent alterations in cerebrospinal fluid Abeta42 levels in cognitively
intact elderly with late-life major depression.
AB - Depression has been linked to Alzheimer's disease as either an increased risk
factor for its development or as a prodromal symptom. The neurobiological basis
for such an association, however, remains poorly understood. Numerous studies
have examined whether changes in amyloid beta (Abeta) metabolism, which are
implicated in the pathogenesis of Alzheimer's disease, are also found in
depression. In this paper, we investigated the relationship between depressive
symptoms and cerebrospinal fluid (CSF) Abeta indices in otherwise healthy,
cognitively normal elderly with late-life major depression (LLMD) and controls
using a longitudinal approach, which is a novel contribution toward the
literature. Significantly lower levels of CSF Abeta42 were observed in the LLMD
group at baseline and were associated with more severe depressive symptoms.
During longitudinal follow-up, the depressed group remained cognitively
unchanged, but was significantly less depressed than at baseline. A greater
improvement in depressive symptoms was associated with increases in CSF Abeta42
levels in both groups. Increases in CSF Abeta42 and Abeta40 were also associated
with increased CSF total-tau levels. Our results suggest that LLMD may be
associated with state-dependent effects of CSF Abeta42 levels. Future studies
should determine whether the association reflects state-dependent changes in
neuronal activity and/or brain amyloid burden in depression.
PMID- 27508980
TI - Human area 5 modulates corticospinal output during movement preparation.
AB - Neuroimaging evidence suggests that human Brodmann area 5 (BA5) within the
superior parietal lobule contributes to movement planning. However, a causal role
for the contribution of BA5 to preparatory processes has yet to be reported. We
used paired-pulse transcranial magnetic stimulation to investigate the influence
of human BA5 on corticospinal excitability during movement preparation in the
context of a GO/NO-GO task. Functional connectivity between BA5 and the
ipsilateral primary motor cortex (M1) was investigated by probing corticospinal
output to the first dorsal interosseous muscle of the right hand. Results
indicate that BA5 influences M1 during movement preparation in a task-specific
manner: motor-evoked potentials are suppressed in the context of a NO-GO versus
GO task. These findings provide evidence that human BA5 participates in movement
preparation and differentiates between whether a movement is withheld or
executed.
PMID- 27508981
TI - Self-Reported California Hospital Palliative Care Program Composition,
Certification, and Staffing Level Are Associated with Lower End-of-Life Medicare
Utilization.
AB - BACKGROUND: California hospitals report palliative care (PC) program
characteristics to the California Office of Statewide Health Planning and
Development (OSHPD), but the significance of this information is unknown.
OBJECTIVE: Our objective was to determine whether self-reported California
hospital PC program characteristics are associated with lower end-of-life (EoL)
Medicare utilization. DESIGN: We performed a cross-sectional study of hospitals
submitting 2012 data to OSHPD and included in the 2012 Dartmouth Atlas of
Healthcare (DAHC) dataset, using statistical hypothesis testing, multivariate
regression, and fuzzy set qualitative comparative analysis. SETTING/SUBJECTS: Our
analysis included 203 hospitals primarily providing general medical-surgical
(GMS) care. MEASUREMENTS: The following measures were available for each
hospital: licensed GMS beds; type of control; presence of an inpatient or
outpatient PC program; number of physicians, nurses, social workers, and
chaplains on the PC team; number of PC-certified staff; percentage of Medicare
decedents dying as inpatients; and average total hospital days, ICU days, and
physician visits per Medicare decedent in the last six months of life. RESULTS:
Investor-owned hospitals have fewer PC programs and higher EoL utilization than
do nonprofit hospitals. Among nonprofit hospitals, small size (substantially
fewer than 150 medical-surgical beds), or large size and having an inpatient PC
program with more than three PC staff per 100 GMS beds, or an interdisciplinary
PC-certified team, is associated with significantly lower EoL hospital
utilization and percentage of deaths occurring in the inpatient setting.
DISCUSSION: Improved program performance associated with higher staffing levels
may be mediated by increased access to and earlier PC interventions. CONCLUSION:
California hospital-reported PC program characteristics are associated with
significantly lower inpatient utilization by Medicare decedents.
PMID- 27508983
TI - Canola Implantation Foreign Body Reaction on the Perineum in a Prepubertal Girl.
From the ISSVD Case Consultation Committee.
PMID- 27508982
TI - Biochemical responses of filamentous algae in different aquatic ecosystems in
South East Turkey and associated water quality parameters.
AB - To the best of our knowledge, any study about biochemical response of filamentous
algae in the complex freshwater ecosystems has not been found in the literature.
This study was designed to explore biochemical response of filamentous algae in
different water bodies from May 2013 to October 2014, using multivariate approach
in the South East of Turkey. Environmental variables were measured in situ: water
temperature, oxygen concentration, saturation, conductivity, salinity, pH, redox
potential, and total dissolved solid. Chemical variables of aqueous samples and
biochemical compounds of filamentous algae were also measured. It was found that
geographic position and anthropogenic activities had strong effect on physico
chemical variables of water bodies. Variation in environmental conditions caused
change in algal biomass composition due to the different response of filamentous
species, also indicated by FTIR analysis. Biochemical responses not only changed
from species to species, but also varied for the same species at different
sampling time and sampling stations. Multivariate analyses showed that heavy
metals, nutrients, and water hardness were found as the important variables
governing the temporal and spatial succession and biochemical compounds.
Nutrients, especially nitrate, could stimulate pigment and total protein
production, whereas high metal content had adverse effects. Amount of
malondialdehyde (MDA), H2O2, total thiol groups, total phenolic compounds,
proline, total carbohydrate, and metal bioaccumulation by filamentous algae could
be closely related with heavy metals in the ecosystems. Significant increase in
MDA, H2O2, total thiol group, total phenolic compounds, and proline productions
by filamentous algae and chlorosis phenomenon seemed to be an important strategy
for alleviating environmental factors-induced oxidative stress as biomarkers.
PMID- 27508984
TI - Is the DSM-V Leading to the Nondiagnosis of Vulvodynia?
PMID- 27508985
TI - Transcriptomic and Proteomic Research To Explore Bruchid-Resistant Genes in
Mungbean Isogenic Lines.
AB - Mungbean (Vigna radiata (L.) Wilczek) is an important rotation legume crop for
human nutrition in Asia. Bruchids (Callosobruchus spp.) currently cause heavy
damage as pests of grain legumes during storage. We used omics-related
technologies to study the mechanisms of bruchid resistance in seeds of the nearly
isogenic lines VC1973A (bruchid-susceptible) and VC6089A (bruchid-resistant). A
total of 399 differentially expressed genes (DEGs) were identified between the
two lines by transcriptome sequencing. Among these DEGs, 251 exhibited high
expression levels and 148 expressed low expression levels in seeds of VC6089A.
Forty-five differential proteins (DPs) were identified by isobaric tags for
relative and absolute quantification (iTRAQ); 21 DPs had higher abundances in
VC6089A, and 24 DPs had higher abundances in VC1973A. According to transcriptome
and proteome data, only three DEGs/DPs, including resistant-specific protein
(g39185), gag/pol polyprotein (g34458), and aspartic proteinase (g5551), were
identified and located on chromosomes 5, 1, and 7, respectively. Both g39185 and
g34458 genes encode a protein containing a BURP domain. In previous research on
bruchid molecular markers, the g39185 gene located close to the molecular markers
of major bruchid-resistant locus may be a bruchid-resistant gene.
PMID- 27508986
TI - Fluorogenic Ubiquinone Analogue for Monitoring Chemical and Biological Redox
Processes.
AB - We report herein the synthesis and characterization of a fluorogenic analogue of
ubiquinone designed to reversibly report on redox reactions in biological
systems. The analogue, H2B-Q, consists of the redox-active quinone segment found
in ubiquinone, 2,3-dimethoxy-1,4-benzoquinone, coupled to a boron-dipyrromethene
(BODIPY) fluorophore segment that both imparts lipophilicity in lieu of the
isoprenyl tail of ubiquinone, and reports on redox changes at the quinone/quinol
segment. Redox sensing is mediated by a photoinduced electron transfer
intramolecular switch. In its reduced dihydroquinone form, H2B-QH2 is highly
emissive in nonpolar media (quantum yields 55-66%), while once oxidized, the
resulting quinone H2B-Q emission is suppressed. Cyclic voltammetry of H2B-Q shows
two reversible, 1-electron reduction peaks at -1.05 V and -1.37 V (vs ferrocene)
on par with those of ubiquinone. Chemical reduction of H2B-Q by NaBH4 resulted in
>200 fold emission enhancement. H2B-QH2 is shown to react with peroxyl radicals,
a form of reactive oxygen species (ROS) as well as to cooperatively interact with
chromanol (the active segment of alpha-tocopherol). Kinetic analysis further
shows the antioxidant reactivity of the nonfluorescent intermediate semiquinone.
We anticipate that the H2B-Q/H2B-QH2 off/on reversible couple may serve as a tool
to monitor chemical redox processes in real-time and in a noninvasive manner.
PMID- 27508987
TI - Chemical composition and acaricidal activity of the essential oils from Vitex
agnus-castus L. (Verbenaceae) and selected monoterpenes.
AB - Tetranychus urticae is considered one of the main plagues in the world. Its
occurrence in Pernambuco was registered for the first time in 1985 and it has
caused considerable damage to the farmers, attacking different cultures of
agricultural interest. The essential oils from different parts of Vitex agnus
castus harvested in the Atlantic forest in the state of Pernambuco, Brazil, were
obtained by hydrodistillation and the acaricidal potential was evaluated against
Tetranychus urticae using two methods under laboratory conditions. Gas
chromatography-mass spectrometry revealed the presence of 47 components
accounting for 98.8 +/- 0.0%, 93.0 +/- 0.1% and 97.4 +/- 1.0% of the essential
oils from the leaves, fruit and inflorescence, respectively. The compounds 1,8
cineole and beta-(E)-farnesene were the major components of the oils from the
leaves (17.6 +/- 0.3% and 13.6 +/- 0.2%, respectively) and fruit (17.5 +/- 0.1%
and 15.4 +/- 0.0%, respectively). beta-(E)-farnesene (13.5 +/- 0.1%) and beta
caryophyllene (11.7 +/- 0.1%) were the major components of the oils from the
flowers. Acaricidal action varied depending on the part of the plant and method
employed. Through fumigation, the oil from the leaves (CL50= 0.61 MUL L-1 of air)
was approximately six fold more toxic than the oil from the fruit. However,
through residual contact, the oil from the fruit (CL50 = 137.11 MULmL-1) was 1.1
fold more toxic than the oil from the leaves. The relationship between the
chemical composition of the oils and acaricidal activity is also presented.
PMID- 27508988
TI - Physicochemical, Antioxidant and Sensory Quality of Brazilian Blueberry Wine.
AB - Currently, Rio Grande do Sul state is the main producer of blueberry in Brazil.
Practically all production is commercialized in fresh state and only a small
portion is subject to processing. The blueberry wine making process is an
alternative to expand the beverage industry and offers to the consumer a value
added product as well as a new market for Brazilian blueberry producers. The
objectives of this study were to produce wines from blueberries and to evaluate
the effect of deacidification (with calcium carbonate) and chaptalization (with
glucose syrup or sucrose) on physicochemical characteristics, antioxidant
content, and sensory parameters. Samples were analyzed for total soluble solids,
pH, total titratable acidity, total sugar content, alcohol content, monomeric and
total anthocyanin, total flavonols, total phenolic compounds and antioxidant
activity by DPPH and FRAP methods. The use of calcium carbonate caused a
reduction in total titratable acidity, while the use of glucose syrup resulted in
wines with low alcohol content. The blueberries wine from Climax and Aliceblue
cultivars had higher content of anthocyanin when produced with glucose syrup. The
use of calcium carbonate and glucose syrup also provided wines more appreciated
by tasters in relation to color. With regard to flavor, George and Aliceblue were
the cultivars with lower preference under the control treatments (without
carbonate and sugar). The presence of phenolic compounds may have provided a
positive influence on wine flavor, once the more preferred wines presented the
greater phenolic content.
PMID- 27508989
TI - Epidemiology of hepatitis B virus in the cities of the northern region of
Espirito Santo, Brazil.
AB - The World Health Organization (WHO) estimates that approximately 2 billion people
worldwide have already had contact with hepatitis B virus (HBV) and 373 million
have become chronic carriers. Hepatitis B is a major cause of chronic hepatitis,
cirrhosis and hepatocellular carcinoma, leading to a large number of deaths
annually. Both viral factors and the host immune response have been implicated in
the pathogenesis and clinical result of HBV infection. Many Brazilian cities,
including the cities of the northern region of the state of Espirito Santo are
located in regions with little health infrastructure. Our study performed an
epidemiological analysis of cases of Hepatitis B in Sao Mateus, using methodology
of Geographic Information System (GIS), aiming to raise the number of disease
cases, establishing preventive measures to control the disease, improving the
quality of life of people affected by this pathology. The city of Sao Mateus had
the largest number of reported cases of hepatitis B northern region of Espirito
Santo. The age group with the highest number of hepatitis B notifications was 20
49 years, mostly females. The major forms of contact with HBV in these cities
were dental treatment, use of injectable medications, surgical procedures and
multiple sexual partners.
PMID- 27508990
TI - The classic episode of biological invasion: Cochliomyia macellaria (Fabricius,
1775) versus Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae) -
evaluation of the biotic potential.
AB - The classic episode of biological invasion: Cochliomyia macellaria (Fabricius,
1775) versus Chrysomya megacephala (Fabricius, 1794) (Diptera: Calliphoridae) -
evaluation of the biotic potential. The biotic of the native fly Cochliomyia
macellaria and the exotic Chrysomya megacephala was compared, through the
reproductive capacity and longevity. The experiment took place in a climatized
chamber, with four repetitions of 15 grouped couples of each species. The
posture, egg mass weight, and death of individuals were observed daily. C.
macellaria showed an average of longevity of 27.72 days while in C. megacephala
the average was 41.96 days. The egg mass weight average per repetition was 0.58 g
and 1.22 g, respectively. These results give a better understanding about the
population dynamics of these species in nature.
PMID- 27508991
TI - Injuries caused by the venomous catfish pintado and cachara (Pseudoplatystoma
genus) in fishermen of the Pantanal region in Brazil.
AB - INTRODUCTION: the fishing activity throughout the Upper Paraguay River Basin has
huge financial and biological importance. This retrospective study investigated
the occurrence of injuries caused by fish of the Pseudoplatystoma genus (spotted
catfish or pintado and striped catfish or cachara) in professional fishermen of
the Pantanal of Mato Grosso do Sul State. METHODS: we collected information
through a questionnaire, showing that fishing is carried out by workers with low
level of education, mainly adults or seniors with low financial gains. RESULTS:
in Miranda town, 126 of 315 fishermen were interviewed and 38 individuals
reported injuries (30.16%). In Corumba town, 355 of 627 fishermen were
interviewed, and 111 (56,61%) reported injuries. The lacerated lesions were the
most common, associate with edema, erythema, radiating pain to the root of the
limb, paresthesias and local necrosis. More rarely, they reported the occurrence
of fever, cardiac arrhythmias and cold sweating. These manifestations may be
associated with late secondary infections or envenomations caused by the toxins
in the stingers of the fish. Many questionable and inappropriate treatments are
used, sometimes aggravating the injuries. CONCLUSIONS: the freshwater
professional fishermen need guidance on first aid measures and prevention of
accidents caused by these venomous fish.
PMID- 27508992
TI - What the largest tadpole feeds on? A detailed analysis of the diet composition of
Pseudis minuta tadpoles (Hylidae, Dendropsophini).
AB - We analyzed the diet of 25 individuals of Pseudis minuta tadpoles which consisted
in debris with more than 30%, follow by diatoms, euglenids, green algae, and
desmids. With regard to the feeding strategy, P. minuta tadpoles are generalist
consumer. The negative correlation between the abundance of items in the
digestive tract and the mouth width indicate an effect of metamorphosis on the
diet.
PMID- 27508993
TI - Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of
Conocarpus erectus Linnaeus in Swiss Albino Mice.
AB - Mangroves represent areas of high biological productivity and it is a region rich
in bioactive substances used in medicine production. Conocarpus erectus
(Combretaceae) known as button mangrove is one of the species found in mangroves
and it is used in folk medicine in the treatment of anemia, catarrh,
conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage,
orchitis, rash, bumps and syphilis. The present study aimed to investigate the
acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice.
The plant material was collected in Vila Velha mangroves, located in Itamaraca
(PE). The material was subjected to a phytochemical screening where extractive
protocols to identify majority molecules present in leaves were used. The
evaluation of acute toxicity of aqueous extract of C. erectus followed the model
of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules
were identified: flavonoids, tannins and saponins. The LD50 was estimated at
2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity
classified in category 5.
PMID- 27508994
TI - On the presence of the subnarial foramen in Prestosuchus chiniquensis
(Pseudosuchia: Loricata) with remarks on its phylogenetic distribution.
AB - Many authors have discussed the subnarial foramen in Archosauriformes. Here
presence among Archosauriformes, shape, and position of this structure is
reported and its phylogenetic importance is investigated. Based on distribution
and the phylogenetic tree, it probably arose independently in Erythrosuchus,
Herrerasaurus, and Paracrocodylomorpha. In Paracrocodylomorpha the subnarial
foramen is oval-shaped, placed in the middle height of the main body of the
maxilla, and does not reach the height of ascending process. In basal loricatans
from South America (Prestosuchus chiniquensis and Saurosuchus galilei) the
subnarial foramen is 'drop-like' shaped, the subnarial foramen is located above
the middle height of the main body of the maxilla, reaching the height of
ascending process, a condition also present in Herrerasaurus ischigualastensis.
These results suggest that this structure might be phylogenetically important and
further investigation with a large set of valid taxa is necessary to properly
evaluate its importance among Archosauria.
PMID- 27508995
TI - Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine
induced lesion of dopaminergic neurons.
AB - The Portulaca oleracea L. (Portulacaceae) is a cosmopolitan species with a wide
range of biological activities, including antioxidant and neuroprotective
actions. We investigated the effects of P. oleracea extracts in a 6
hydroxydopamine rat model of Parkinson's disease, a debilitating disorder without
effective treatments. Chemical profiles of aqueous and ethanolic extracts of
whole plant were analyzed by thin layer chromatography and the antioxidant
activity was assessed by 2,2-diphenyl-1-picrilhidrazila method. Male Wistar rats
received intrastriatal 6-hydroxydopamine and were treated with vehicle or
extracts (oral, 200 and 400 mg/kg) daily for two weeks. The behavioral open field
test was conducted at days 1 and 15. Immunohistochemical analysis was performed 4
weeks after surgery to quantify tyrosine-hydroxylase cell counts in the
substantia nigra pars compacta. Extracts presented antioxidant activity in
concentrations above 300 ug/kg. The chromatographic analysis revealed the
presence of Levodopa, alkaloids, flavonoids, saponins, tannins, terpenoids and
polysaccharides. Both extracts improved motor recovery 15 days after lesion and
protected from tyrosine-hydroxylase cell loss after 4 weeks, but these effects
were more evident for the aqueous extract. Because the dopamine precursor is
present, in addition to antioxidant compounds and neuroprotective effects, P.
oleracea can be considered as potential strategy for treating Parkinson's
disease.
PMID- 27508996
TI - Inactivated Parapoxvirus ovis as inducer of immunity in silver catfish (Rhamdia
quelen).
AB - Molecules with immune modulating activity are ubiquitously distributed in nature
and their impact on aquaculture has been exploited in order to increase fish
resistance to pathogens. Here, we investigated the effect of inactivated
Parapoxvirus ovis (iPPVO) on blood cells and innate and acquired immune response
of silver catfish (Rhamdia quelen). iPPVO inoculation had no effect on
respiratory burst activity; however, following iPPVO inoculation, we observed a
significant decrease on circulating monocytes concomitantly with an increased
number of heterophilic granulocytes and thrombocytes, which are the main cells
involved in innate immunity and provide connection with acquired immunity. Fish
inoculated with a combination of bovine serum albumin (BSA) + iPPVO had
significantly higher levels of antibodies to BSA compared to fish inoculated with
BSA alone, but lower than fish inoculated with BSA + Freund's incomplete adjuvant
(FIA). These findings points to the potential usefulness of iPPVO as
immunomodulator in fish and instigate further research to identify its component
that interact with immune cells and that could be exploited as adjuvants in fish.
PMID- 27508998
TI - Evaluation of Liposome, Heat-Killed Mycobacterium w, and Alum Adjuvants in the
Protection Offered by Different Combinations of Recombinant HA, NP proteins, and
M2e Against Homologous H5N1 Virus.
AB - Continued evolution of highly pathogenic H5N1 viruses causing high mortality in
humans obviates need for broadly cross-reactive vaccines. For this, hemagglutinin
(HA) inducing specific protective antibodies, highly conserved nucleoprotein
(NP), and ectodomain of matrix (M2e) protein, either singly or in combination,
were evaluated in BALB/c mice. Recombinant HA and NP (baculovirus system) and M2e
(synthetic peptide) and 3 adjuvants, that is, liposomes, Mw (heat killed
Mycobacterium w), and alum were utilized for the homologous virus challenge.
Additional immunogens included liposome-encapsulated HA/NP proteins and
corresponding DNAs. Mice groups received two doses of respective formulations
given at 3-week intervals and challenged intranasally with 100LD50 of H5N1 virus
strain. Dynamics of weight loss, lung viral load, titres of IgG-anti-HA, NP, and
M2e antibodies (ELISA), and IgG-subtype analysis was done. Two doses of all the
formulations led to 100% seroconversion against the immunogens evaluated (100%
seroconversion after the first dose in majority). Antibody titres against the
components were dependent on the adjuvant and combination. HA-driven Th2 response
with all the adjuvants, balanced Th1/Th2 response to NP protein, and Th2-bias
with alum were noted. Low anti-M2e antibody titres did not allow subtype
analysis. On challenge, complete protection was observed with Mw-HA, alum-HA+NP,
Lipo-HA+NP+M2e, alum-HA+NP+M2e, and HA-DP formulations with 12-fold, 8-fold, 720
fold, 17-fold, and no reduction, respectively, in lung viral load. In conclusion,
the results identify several adjuvant-immunogen combinations conferring 100%
protection in mice that need further evaluation in higher animals.
PMID- 27508997
TI - Recognition memory and DNA damage in undernourished young rats.
AB - This study evaluated the recognition memory and the levels of DNA damage (blood
and hippocampus) in undernourished young Wistar rats. The experiment was
conducted along 14-week with rodents divided in control group (CG, n=8) and
undernourished group (UG, n=12) which was submitted to caloric restriction.
Nutritional status for undernutrition was defined by Body Mass Index (BMI)
<=0.45g/cm2 and by weighting the organs/tissue (liver, spleen, intestine,
peritoneal fat, kidney and encephalon). The Novel Object Recognition Test
assessed recognition memory and the Comet Assay evaluated the levels of DNA
damage. Student t test, 2-way ANOVA and Pearson's correlation analysis were used
and the significance level was of p<0.05. The UG showed lower BMI and
organ/tissue weights than CG (p<0.001). In short-term memory, the recognition
rate was higher in the UG (p<0.05), only after 4 weeks. In the long-term memory,
again recognition rate was higher in the UG than the CG, after 4 weeks (p<0.001)
and 14 weeks (p<0.01). The UG showed decreased levels of DNA damage in the blood
(p<0.01) and increased levels in the hippocampus (p<0.01). We concluded in this
study that the undernutrition by caloric restriction did not cause impairment in
recognition memory, however induced DNA damage in the hippocampus.
PMID- 27508999
TI - The Ross Procedure in Adults: Long-Term Results of Homografts and Stentless
Xenografts for Pulmonary Valve Replacement.
AB - Background The Ross procedure is an established method to treat aortic valve
disease, offering excellent hemodynamic characteristics, growth potential, low
risk of thromboembolism and no need for anticoagulation. Limitation of homograft
quality and availability led to the use of different stentless xenografts. Long
term outcome and implications are yet to be addressed. Methods Forty five adult
patients (mean age 38.8 +/- 9.6 years) with aortic valve stenosis and/or
insufficiency, who underwent the Ross procedure between 1995 and 2002 were
identified for long-term evaluation. Patients younger than 18 years, with
previous heart surgery and endocarditis were excluded. Stentless xenografts were
used in 22 cases (Group X) and homografts in 23 cases (Group H). After review of
the patients' history, morbidity and mortality were analyzed and risk
stratification was performed. Results Between groups, baseline characteristics
and operative data did not differ significantly. Total follow-up was 621.0
patient-years and 98.8% complete. Overall freedom from reoperation at 15 years
was 68.4 +/- 10.6% in group X and 85. +/- 7.9% in group H (p = 0.09),
respectively. Freedom from aortic valve reoperation at 15 years was comparable
(83.9 +/- 8.5% in group X and 85.3 +/- 7.9% in group H, p = 0.61), whereas
freedom from pulmonary valve reoperation at 15 years was significantly lower in
group X (78.9 +/- 9.4% versus 100%, p = 0.02). Long-term survival at 15 years was
79.7 +/- 9.3% in group X and 94.4 +/- 5.4% in group H (p = 0.07), respectively.
Conclusions Stentless xenografts used as pulmonary valve substitute in the Ross
procedure led to lower freedom from pulmonary valve reoperation compared with
homografts. Additionally, there was a trend to inferior long-term survival with
xenografts. Therefore, homografts should remain the preferred option for
pulmonary valve replacement in the Ross procedure.
PMID- 27509000
TI - Individualized Surgical Treatments for Children with Ebstein Anomaly.
AB - Objective Ebstein anomaly is a rare type of tricuspid malformation. The present
surgical methods to resolve this anomaly include tricuspid valvuloplasty,
palliative surgery, and tricuspid valve replacement. The purpose of this study
was to evaluate the short- and midterm outcomes of different surgical treatments
among children with Ebstein anomaly. Methods This was a retrospective study of
136 Ebstein anomaly patients undergoing surgery at our institution from January,
2006 to August, 2015. This cohort included 118 patients receiving tricuspid
valvuloplasty, 14 patients receiving palliative surgery and 4 patients receiving
tricuspid valve replacement. Results There were two in-hospital deaths and one
delayed death 6 months after bidirectional cavopulmonary shunt during a second
stage operation; thus, the mortality rate was 2.2% (3/136). The follow-up
variables included echocardiography, chest radiography, oxygen saturation, and
cardiac function. After a mean follow-up duration of 35.8 +/- 16.5 months (range:
6-98 months), all survivors had no indications for reoperation; the oxygen
saturation following radical surgery and palliative surgery was 95 to 100% and 85
to 95%, respectively. Most of the patients exhibited an improved New York Heart
Association (NYHA) functional class from III or IV preoperatively to I or II at
follow-up; only two patients who underwent the Fontan procedure continued to
exhibit NYHA functional class III. In most patients, tricuspid regurgitation (TR)
degree decreased from moderate or severe preoperatively to mild or moderate at
follow-up and only six patients continued to exhibit severe TR at follow-up.
Conclusions Individualization of surgical methods based on different indications,
including age, associated malformations, tricuspid anatomy, cardiac function, and
intraoperative status, could effectively improve the outcomes of Ebstein anomaly
patients.
PMID- 27509001
TI - Data Science Meets the Clinician: Challenges and Future Directions.
AB - In the last three decades a profound transformation of the medical profession has
taken place. The modern clinician is required to consume vast amounts of
information from clinical studies, critically reviewing evidence that may or may
not lead to changes in clinical practice. The present article presents some
challenges that this era of information poses to clinicians and patients.
PMID- 27509002
TI - Modified Transsubxiphoid Thoracoscopic Extended Thymectomy in Patients with
Myasthenia Gravis.
AB - We developed a new minimally invasive thoracoscopic technique of extended
thymectomy for myasthenia gravis by combining a subxiphoid incision with dual
costal margin incisions. In our experience of 31 consecutive cases, this
procedure provides a good operative view in the neck region and makes
verification of the bilateral phrenic nerves easy. All the patients recovered
smoothly with less trauma, less bleeding, less complication, and good cosmetic
results. This modified transsubxiphoid approach is a satisfactory procedure for
performing extended thymectomy in patients with myasthenia gravis.
PMID- 27509003
TI - Identifying areas of need relative to liver disease: geographic clustering within
a health service district.
AB - Background Many people with chronic liver disease (CLD) are not detected until
they present to hospital with advanced disease, when opportunities for
intervention are reduced and morbidity is high. In order to build capacity and
liver expertise in the community, it is important to focus liver healthcare
resources in high-prevalence disease areas and specific populations with an
identified need. The aim of the present study was to examine the geographic
location of people seen in a tertiary hospital hepatology clinic, as well as
ethnic and sociodemographic characteristics of these geographic areas. Methods
The geographic locations of hepatology out-patients were identified via the out
patient scheduling database and grouped into statistical area (SA) regions for
demographic analysis using data compiled by the Australian Bureau of Statistics.
Results During the 3-month study period, 943 individuals from 71 SA Level 3
regions attended clinic. Nine SA Level 3 regions accounted for 55% of the entire
patient cohort. Geographic clustering was seen especially for people living with
chronic hepatitis B virus. There was a wide spectrum of socioeconomic advantage
and disadvantage in areas with high liver disease prevalence. Conclusions The
geographic area from which people living with CLD travel to access liver health
care is extensive. However, the greatest demand for tertiary liver disease
speciality care is clustered within specific geographic areas. Outreach programs
targeted to these areas may enhance liver disease-specific health service
resourcing. What is known about the topic? The demand for tertiary hospital
clinical services in CLD is rising. However, there is limited knowledge about the
geographic areas from which people living with CLD travel to access liver
services, or the ethnic, socioeconomic and education characteristics of these
areas. What does this paper add? The present study demonstrates that a
substantial proportion of people living with CLD and accessing tertiary hospital
liver services are clustered within specific geographic areas. The most striking
geographic clustering was seen for people living with chronic hepatitis B, in
regions with a relatively high proportion of people born in Vietnam and China. In
addition to ethnicity, the data show an apparent ecological association between
liver disease and both socioeconomic and educational and/or occupational
disadvantage. What are the implications for practitioners? Identifying where
demand for clinical services arises is an important step for service planning and
preparing for potential outreach programs to optimise community-based care. It is
likely that outreach programs to engage and enhance primary care services in
geographic areas from which the greatest demand for tertiary liver disease
speciality care arises would yield greater relative return on investment than non
targeted outreach programs.
PMID- 27509005
TI - Correction: Enhanced photocatalytic activity of a self-stabilized synthetic
flavin anchored on a TiO2 surface.
AB - Correction for 'Enhanced photocatalytic activity of a self-stabilized synthetic
flavin anchored on a TiO2 surface' by Manjula Pandiri et al., Phys. Chem. Chem.
Phys., 2016, 18, 18575-18583.
PMID- 27509004
TI - 1,2,3-Triazoles as Amide Bioisosteres: Discovery of a New Class of Potent HIV-1
Vif Antagonists.
AB - RN-18 based viral infectivity factor (Vif), Vif antagonists reduce viral
infectivity by rescuing APOBEC3G (A3G) expression and enhancing A3G-dependent Vif
degradation. Replacement of amide functionality in RN-18 (IC50 = 6 MUM) by
isosteric heterocycles resulted in the discovery of a 1,2,3-trizole, 1d (IC50 =
1.2 MUM). We identified several potent HIV-1 inhibitors from a 1d based library
including 5ax (IC50 = 0.01 MUM), 5bx (0.2 MUM), 2ey (0.4 MUM), 5ey (0.6 MUM), and
6bx (0.2 MUM).
PMID- 27509006
TI - Effects of the Mediterranean Diet on Cardiovascular Outcomes-A Systematic Review
and Meta-Analysis.
AB - BACKGROUND: A Mediterranean dietary pattern is widely recommended for the
prevention of chronic disease. We sought to define the most likely effects of the
Mediterranean diet on vascular disease and mortality. METHODS: We searched
MEDLINE, EMBASE and the Cochrane Central Register without language restriction
for randomized controlled trials comparing Mediterranean to control diets. Data
on study design, patient characteristics, interventions, follow-up duration,
outcomes and adverse events were sought. Individual study relative risks (RR)
were pooled to create summary estimates. RESULTS: Six studies with a total of
10950 participants were included. Effects on major vascular events (n = 477),
death (n = 693) and vascular deaths (n = 315) were reported for 3, 5 and 4
studies respectively. For one large study (n = 1000) there were serious concerns
about the integrity of the data. When data for all studies were combined there
was evidence of protection against major vascular events (RR 0.63, 95% confidence
interval 0.53-0.75), coronary events (0.65, 0.50-0.85), stroke (0.65, 0.48-0.88)
and heart failure (0.30, 0.17-0.56) but not for all-cause mortality (1.00, 0.86
1.15) or cardiovascular mortality (0.90, 0.72-1.11). After the study of concern
was excluded the benefit for vascular events (0.69, 0.55-0.86) and stroke (0.66,
0.48-0.92) persisted but apparently positive findings for coronary events (0.73,
0.51-1.05) and heart failure (0.25, 0.05-1.17) disappeared. CONCLUSION: The
Mediterranean diet may protect against vascular disease. However, both the
quantity and quality of the available evidence is limited and highly variable.
Results must be interpreted with caution.
PMID- 27509007
TI - Hospitalists and the Decline of Comprehensive Care.
PMID- 27509008
TI - Trends and variation in management and outcomes of very low-birth-weight infants
with patent ductus arteriosus.
AB - BACKGROUND: We examined recent trends and interhospital variation in use of
indomethacin, ibuprofen, and surgical ligation for patent ductus arteriosus (PDA)
in very-low-birth-weight (VLBW) infants. METHODS: Included in this retrospective
study of the Pediatric Hospital Information System database were 13,853 VLBW
infants from 19 US children's hospitals, admitted at age < 3 d between 1 January
2005 and 31 December 2014. PDA management and in-hospital outcomes were examined
for trends and variation. RESULTS: PDA was diagnosed in 5,719 (42%) VLBW infants.
Cyclooxygenase inhibitors and/or ligation were used in 74% of infants with PDA
overall, however studied hospitals varied greatly in PDA management. Odds of any
cyclooxygenase inhibitor or surgical treatment for PDA decreased 11% per year
during the study period. This was temporally associated with improved survival
but also with increasing bronchopulmonary dysplasia, periventricular
leukomalacia, retinopathy of prematurity, and acute renal failure in unadjusted
analyses. There was no detectable correlation between hospital-specific changes
in PDA management and hospital-specific changes in outcomes of preterm birth
during the study period. CONCLUSION: Use of cyclooxygenase inhibitors and
ligation for PDA in VLBW infants decreased over a 10-y period at the studied
hospitals. Further evidence is needed to assess the impact of this change in PDA
management.
PMID- 27509010
TI - Factors associated with the implementation of programs for drug abuse prevention
in schools.
AB - OBJECTIVE: To analyze if characteristics of managers, schools, and curriculum are
associated with the implementation of programs for drug abuse prevention in
elementary and high schools. METHODS: Cross-sectional study, with random sample
of 263 school managers. Data were collected between 2012 and 2013 by a program
that sends forms via internet. A closed self-filling questionnaire was applied
online. Statistical analysis included Chi-square tests and logistic regression
models. The outcome variable was the presence of program for drug abuse
prevention inserted in the daily life and educational program of the school. The
explanatory variables were divided into: demographic data of the manager;
characteristics of the school and of the curriculum; health education; and drug
use in the school. RESULTS: We found that 42.5% (95%CI 36.1-49.1) of the
evaluated schools had programs for drug abuse prevention. With the multiple
logistic regression model, we observed that the more time the manager has worked
with education, the chance of the school having a program increased at about
4.0%. Experimenting with innovative teaching techniques also increased at about
six times the chance of the school developing a program for drug abuse
prevention. The difficulties in the implementation of the programs were more
present in state and municipal schools, when compared with private schools, due
to, for instance: lack of teaching materials, lack of money, and competing
demands for teaching other subjects. CONCLUSIONS: The implementation of programs
for drug abuse prevention in the city of Sao Paulo is associated with the
experience of the manager in education and with the teaching strategies of the
school. OBJETIVO: Analisar se caracteristicas dos dirigentes, das escolas e do
curriculo escolar estao associadas a implantacao de programas de prevencao ao uso
de drogas nas escolas do ciclo fundamental II e medio. METODOS: Estudo
transversal, com amostra aleatoria sistematica de 263 dirigentes escolares. Os
dados foram coletados nos anos de 2012 e 2013 por meio de um programa de envio de
formularios pela internet. Aplicou-se questionario fechado, de autopreenchimento
on-line. A analise estatistica incluiu testes Qui-quadrado e modelos de regressao
logistica. A variavel desfecho foi a presenca de programa de prevencao ao uso de
drogas inserido no cotidiano e no programa pedagogico da escola. As variaveis
explicativas foram divididas em: dados demograficos do dirigente; caracteristicas
da escola e do curriculo; educacao em saude; e consumo de drogas na escola.
RESULTADOS: Constatou-se que 42,5% (IC95% 36,1-49,1) das escolas avaliadas
possuiam programa de prevencao ao uso de drogas. Com o modelo de regressao
logistica multipla, observou-se que, a cada ano de atuacao do dirigente na
educacao, a chance de a escola ter um programa aumentava em aproximadamente 4,0%.
O fato de experimentar tecnicas de ensino inovadoras tambem aumentou em cerca de
seis vezes a chance de a escola desenvolver um programa de prevencao ao uso de
drogas. As dificuldades na implantacao dos programas foram mais presentes nas
redes estadual e municipal, quando comparadas a rede privada, destacando-se: a
falta de material didatico, a falta de dinheiro e as demandas concorrentes para
ensino de outras disciplinas. CONCLUSOES: A implantacao de programas de prevencao
ao uso de drogas no municipio de Sao Paulo esta associada a experiencia do
dirigente escolar na educacao e nas estrategias de ensino da escola.
PMID- 27509009
TI - Postnatal growth restriction augments oxygen-induced pulmonary hypertension in a
neonatal rat model of bronchopulmonary dysplasia.
AB - BACKGROUND: Prematurity and fetal growth restriction are risk factors for
pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD).
Neonatal rats develop PH and vascular remodeling when exposed to hyperoxia. We
hypothesize that postnatal growth restriction (PNGR) due to under-nutrition
increases the severity of PH induced by hyperoxia in neonatal rats. METHODS: Pups
were randomized at birth to litters maintained in room air or 75% oxygen
(hyperoxia), together with litters of normal milk intake (10 pups) or PNGR (17
pups). After 14 d, right ventricular hypertrophy (RVH) was assessed by Fulton's
index (right ventricular weight/left ventricular plus septal weight) and PH by
echocardiography. Lungs were analyzed by immunohistochemistry, morphometrics,
western blotting, and metabolomics. RESULTS: Hyperoxia and PNGR each
significantly increased pulmonary arterial pressure, RVH and pulmonary arterial
medial wall thickness, and significantly decreased pulmonary vessel number. These
changes were significantly augmented in pups exposed to both insults. Hyperoxia
and PNGR both significantly decreased expression of proteins involved in lung
development and vasodilation. CONCLUSION: PNGR induces right ventricular and
pulmonary vascular remodeling and augments the effects of oxygen in neonatal
rats. This may be a powerful tool to investigate the mechanisms that induce PH in
low-birth-weight preterm infants with BPD.
PMID- 27509011
TI - Evaluation in health: participatory methodology and involvement of municipal
managers.
AB - OBJECTIVE: To analyze scopes and limits of the use of participatory methodology
of evaluation with municipal health managers and administrators. METHODS:
Qualitative research with health policymakers and managers of the Comissao
Intergestores Regional (CIR - Regional Interagency Commission) of a health region
of the state of Sao Paulo in Brazil. Representatives from seven member cities
participated in seven workshops facilitated by the researchers, with the aim of
assessing a specific problem of the care line, which would be used as a tracer of
the system integrality. The analysis of the collected empirical material was
based on the hermeneutic-dialectic methodology and aimed at the evaluation of the
applied participatory methodology, according to its capacity of promoting a
process of assessment capable to be used as a support for municipal management.
RESULTS: With the participatory approach of evaluation, we were able to promote
in-depth discussions with the group, especially related to the construction of
integral care and to the inclusion of the user's perspective in decision-making,
linked to the search for solution to concrete problems of managers. By joint
exploration, the possibility of using data from electronic information systems
was opened, as well as information coming directly from the users of the
services, to enhance discussions and negotiations between partners. The
participants were disbelievers of the replication potential of this type of
evaluation without the direct monitoring of the academy, given the difficulty of
organizing the process in everyday life, already taken by emergency and political
issues. CONCLUSIONS: Evaluations of programs and services carried out within the
Regional Interagency Commission, starting from the local interest and
facilitating the involvement of its members by the use of participatory
methodologies, can contribute to the construction of integral care. To the extent
that the act of evaluating stay invested with greater significance to the local
actors, its involvement with the evaluations at the federal level can also be
stimulated. OBJETIVO: Analisar alcances e limites do uso de metodologia
participativa de avaliacao junto a gestores e gerentes municipais de saude.
METODOS: Pesquisa qualitativa com gestores e gerentes de saude da Comissao
Intergestores Regional de uma regiao de saude do estado de Sao Paulo.
Representantes de sete municipios membros participaram de sete oficinas
facilitadas pelos pesquisadores, com o objetivo de avaliar um problema especifico
da linha de cuidados sob a perspectiva da integralidade. A analise do material
empirico coletado baseou-se na metodologia hermeneutica-dialetica e visou a
avaliacao da metodologia participativa aplicada, segundo sua capacidade de
promover um processo de avaliacao passivel de ser utilizado como suporte a gestao
municipal. RESULTADOS: Com a abordagem participativa de avaliacao, foi possivel
promover debates em profundidade com o grupo, principalmente relacionados a
construcao da integralidade da atencao e a inclusao da perspectiva do usuario na
tomada de decisao, de forma vinculada a busca de solucao para problemas concretos
dos gestores. Mediante a exploracao conjunta, foi aberta a possibilidade de
utilizacao de dados advindos dos sistemas eletronicos de informacao, bem como de
informacoes advindas diretamente dos usuarios dos servicos, para enriquecer
debates e negociacoes entre parceiros. Os participantes se mostraram descrentes
do potencial de replicacao deste tipo de avaliacao sem o acompanhamento direto da
academia, dada a dificuldade de organizacao do processo no cotidiano, ja tomado
por questoes emergenciais e politicas. CONCLUSOES: Avaliacoes de programas e
servicos realizadas no ambito da Comissao Intergestores Regional, partindo do
interesse local e facilitando o envolvimento de seus membros pelo uso de
metodologias participativas, podem contribuir para a construcao da integralidade
do cuidado. Na medida em que o ato de avaliar fique investido de maior
significado para os atores locais, seu envolvimento com as avaliacoes em nivel
federal podera ser tambem estimulado.
PMID- 27509012
TI - Community resilience and Chagas disease in a rural region of Mexico.
AB - OBJECTIVE: To explore the pillars of community resilience in a region where
Chagas disease is endemic, with the aim of promoting participatory processes to
deal with this condition from the resilience of the population. METHODS:
Qualitative study using ethnographic record and six interviews of focus groups
with young people, women and men. The research was carried out in a rural area of
the state of Morelos, Mexico, between 2006 and 2007. We carried out educational
sessions with the population in general, so that residents could identify the
relationship between the vector Triatoma pallidipennis, the parasite (Trypanosoma
cruzi), symptoms, and preventive actions for Chagas disease. The ethnographic
record and groups were analyzed based on Taylor and Bogdan's modification, and
the focus was to understand the socio-cultural meanings that guide the speeches
and activities of residents in relation to the pillars of community resilience.
RESULTS: The population felt proud of belonging to that location and three
pillars of community resilience were clearly identified: collective self-esteem,
cultural identity, and social honesty. Having these pillars as bases, we promoted
the participation of the population concerning Chagas disease, and a Community
Action Group was formed with young people, adult men and women, and social
leaders. This Group initiated actions of epidemiological and entomological
surveillance in the community to deal with this problem. CONCLUSIONS: It is
necessary to create more experiences that deepen the understanding of the pillars
of community resilience, and how they contribute to enhance participation in
health to deal with Chagas disease. OBJETIVO: Explorar los pilares de la
resiliencia comunitaria en una region en la que la enfermedad de Chagas es
endemica, con la finalidad de partir de la resiliencia de la poblacion para
impulsar procesos participativos para enfrentar este padecimiento. METODOS:
Estudio cualitativo que utilizo registro etnografico y seis entrevistas de grupos
focales con jovenes, mujeres y hombres adultos. La investigacion se efectuo en
una localidad rural del Estado de Morelos, Mexico, entre 2006 y 2007. Se
efectuaron sesiones educativas con la poblacion en general, para que los
habitantes identificaran la relacion entre el vector Triatoma pallidipennis, el
parasito (Trypanosoma cruzi), la sintomatologia y acciones preventivas para la
enfermedad de Chagas. El registro etnografico y los grupos fueron analizados con
base en una modificacion de Taylor y Bogdan, y el foco fue comprender los
significados socioculturales que guian los discursos y actividades de los
pobladores en relacion a los pilares de la resiliencia comunitaria. RESULTADOS:
La poblacion se sentia orgullosa de pertenecer a esa localidad y se identificaron
con claridad tres pilares de la resiliencia comunitaria: autoestima colectiva,
identidad cultural y honestidad social. Tomando como base estos pilares, se
impulso la participacion de la poblacion en torno a la enfermedad de Chagas, y se
formo un Grupo de Accion Comunitaria con jovenes, hombres y mujeres adultos, y
lideres sociales. Este Grupo inicio acciones de vigilancia epidemiologica y
entomologica en la comunidad para hacer frente a esta problematica. CONCLUSIONES:
Es necesario generar mas experiencias que profundicen en la comprension de los
pilares de resiliencia comunitaria, y en la manera en que estos contribuyen a
potenciar la participacion en salud para enfrentar la enfermedad de Chagas.
PMID- 27509013
TI - Linking Oxidative Stress and Magnitude of Compensatory Responses with Life-Stage
Specific Differences in Sensitivity of White Sturgeon (Acipenser transmontanus)
to Copper or Cadmium.
AB - Sensitivity of white sturgeon (Acipenser transmontanus) to copper (Cu) or cadmium
(Cd) has been shown to significantly differ as a function of life-stage. This
study investigated oxidative stress, metal homeostasis, and associated
compensatory responses as potential mechanisms of this sensitivity pattern in
three early life-stages. Sturgeon were most sensitive to Cu at 15 days post hatch
(dph), which was accompanied by a significant increase in lipid peroxidation
(LPO). Genes involved with amelioration of oxidative stress were significantly
less inducible at this stage than in older, less sensitive fry. At 48 dph, acute
lethality of sturgeon exposed to Cd was greatest and body LPO was significantly
induced by 3.5-fold at 5 MUg Cd/L. Moreover, there was a small but significant
increase in antioxidative responses. At 139 dph, sturgeon were most tolerant to
Cu and Cd and accumulation of these metals was least. Also, expression of
metallothionein (MT) and apoptotic genes were greatest while expression of metal
transporters was reduced and concentration of LPO was not different from
controls. Our results suggest that life-stage specific sensitivity of white
sturgeon to metals is complex, encompassing differences in the ability to mount
compensatory responses important for metal homeostasis and combating oxidative
stress and concomitant damages.
PMID- 27509014
TI - Dynamic Interplay between the Transcriptome and Methylome in Response to
Oxidative and Alkylating Stress.
AB - In recent years, it has been shown that free radicals not only react directly
with DNA but also regulate epigenetic processes such as DNA methylation, which
may be relevant within the context of, for example, tumorigenesis. However, how
these free radicals impact the epigenome remains unclear. We therefore
investigated whether methyl and hydroxyl radicals, formed by tert-butyl
hydroperoxide (TBH), change temporal DNA methylation patterns and how this
interferes with genome-wide gene expression. At three time points, TBH-induced
radicals in HepG2 cells were identified by electron spin resonance spectroscopy.
Total 5-methylcytosine (5mC) levels were determined by liquid chromatography and
tandem mass spectrometry and genome-wide changes in 5mC and gene expression by
microarrays. Induced methylome changes rather represent an adaptive response to
the oxidative stress-related reactions observed in the transcriptome. More
specifically, we found that methyl radicals did not induce DNA methylation
directly. An initial oxidative and alkylating stress-related response of the
transcriptome during the early phase of TBH treatment was followed by an
epigenetic response associated with cell survival signaling. Also, we identified
genes of which the expression seems directly regulated by DNA methylation. This
work suggests an important role of the methylome in counter-regulating primary
oxidative and alkylating stress responses in the transcriptome to restore normal
cell function. Altogether, the methylome may play an important role in counter
regulating primary oxidative and alkylating stress responses in the transcriptome
presumably to restore normal cell function.
PMID- 27509015
TI - "Click" Chemistry-Tethered Hyaluronic Acid-Based Contact Lens Coatings Improve
Lens Wettability and Lower Protein Adsorption.
AB - Improving the wettability of and reducing the protein adsorption to contact
lenses may be beneficial for improving wearer comfort. Herein, we describe a
simple "click" chemistry approach to surface functionalize poly(2-hydroxyethyl
methacrylate) (pHEMA)-based contact lenses with hyaluronic acid (HA), a
carbohydrate naturally contributing to the wettability of the native tear film. A
two-step preparation technique consisting of laccase/TEMPO-mediated oxidation
followed by covalent grafting of hydrazide-functionalized HA via simple immersion
resulted in a model lens surface that is significantly more wettable, more water
retentive, and less protein binding than unmodified pHEMA while maintaining the
favorable transparency, refractive, and mechanical properties of a native lens.
The dipping/coating method we developed to covalently tether the HA wetting agent
is simple, readily scalable, and a highly efficient route for contact lens
modification.
PMID- 27509017
TI - Quantitative Analysis of the Cervical Texture by Ultrasound and Correlation with
Gestational Age.
AB - OBJECTIVES: Quantitative texture analysis has been proposed to extract robust
features from the ultrasound image to detect subtle changes in the textures of
the images. The aim of this study was to evaluate the feasibility of quantitative
cervical texture analysis to assess cervical tissue changes throughout pregnancy.
METHODS: This was a cross-sectional study including singleton pregnancies between
20.0 and 41.6 weeks of gestation from women who delivered at term. Cervical
length was measured, and a selected region of interest in the cervix was
delineated. A model to predict gestational age based on features extracted from
cervical images was developed following three steps: data splitting, feature
transformation, and regression model computation. RESULTS: Seven hundred images,
30 per gestational week, were included for analysis. There was a strong
correlation between the gestational age at which the images were obtained and the
estimated gestational age by quantitative analysis of the cervical texture (R =
0.88). DISCUSSION: This study provides evidence that quantitative analysis of
cervical texture can extract features from cervical ultrasound images which
correlate with gestational age. Further research is needed to evaluate its
applicability as a biomarker of the risk of spontaneous preterm birth, as well as
its role in cervical assessment in other clinical situations in which cervical
evaluation might be relevant.
PMID- 27509018
TI - Praying until Death: Apostolicism, Delays and Maternal Mortality in Zimbabwe.
AB - Religion affects people's daily lives by solving social problems, although it
creates others. Female sexual and reproductive health are among the issues most
affected by religion. Apostolic sect members in Zimbabwe have been associated
with higher maternal mortality. We explored apostolic beliefs and practices on
maternal health using 15 key informant interviews in 5 purposively selected
districts of Zimbabwe. Results show that apostolicism promotes high fertility,
early marriage, non-use of contraceptives and low or non-use of hospital care. It
causes delays in recognizing danger signs, deciding to seek care, reaching and
receiving appropriate health care. The existence of a customized spiritual
maternal health system demonstrates a huge desire for positive maternal health
outcomes among apostolics. We conclude that apostolic beliefs and practices
exacerbate delays between onset of maternal complications and receiving help,
thus increasing maternal risk. We recommend complementary and adaptive approaches
that address the maternal health needs of apostolics in a religiously sensitive
manner.
PMID- 27509019
TI - A systematic review of the psychometric properties of bronchiolitis assessment
tools.
AB - AIM: The aim of this study was to assess the psychometric properties of tools
developed for the purpose of assessing infants with bronchiolitis. BACKGROUND:
Bronchiolitis is the leading cause of hospitalization in infants under the age of
1 year. Several bronchiolitis assessment tools have been developed primarily for
use in randomized control trials of medical treatments for infants with
bronchiolitis, however, the reliability and validity of many of these tools is
not well reported. DESIGN: Systematic review. DATA SOURCES: CINAHL, MEDLINE,
EMBASE and PubMed electronic databases were searched between January 1960
December 2015 using the key words 'bronchiolitis' and 'assessment' or 'screen' or
'tool' or 'scale' or 'score'. REVIEW METHODS: A systematic review of the
psychometric properties of bronchiolitis assessment tools was undertaken using
the COSMIN checklist. RESULTS: Fourteen studies meeting the inclusion criteria
were reviewed and the methodological quality of the studies and reported
psychometric properties of 11 instruments were assessed. Overall, the reliability
and validity of bronchiolitis assessment tools was poorly established. Although
several studies reported that their tools had good inter-rater reliability, the
methodological quality of these studies was generally poor. Only one study
underwent psychometric testing that was assessed as being of excellent quality.
The Respiratory Distress Assessment Index was deemed to have undergone the most
rigorous psychometric testing but had poor to moderate construct validity and
considerable test-retest error. CONCLUSION: Current bronchiolitis assessment
tools lack clearly established reliability and validity and may not be sensitive
to clinically meaningful outcomes for patients.
PMID- 27509020
TI - Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints
of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever
Patients.
AB - CELADEN was a randomized placebo-controlled trial of 50 patients with confirmed
dengue fever to evaluate the efficacy and safety of celgosivir (A study
registered at ClinicalTrials.gov, number NCT01619969). Celgosivir was given as a
400 mg loading dose and 200 mg bid (twice a day) over 5 days. Replication
competent virus was measured by plaque assay and compared to reverse
transcription quantitative PCR (qPCR) of viral RNA. Pharmacokinetics (PK)
correlations with viremia, immunological profiling, next generation sequence
(NGS) analysis and hematological data were evaluated as exploratory endpoints
here to identify possible signals of pharmacological activity. Viremia by plaque
assay strongly correlated with qPCR during the first four days. Immunological
profiling demonstrated a qualitative shift in T helper cell profile during the
course of infection. NGS analysis did not reveal any prominent signature that
could be associated with drug treatment; however the phylogenetic spread of
patients' isolates underlines the importance of strain variability that may
potentially confound interpretation of dengue drug trials conducted during
different outbreaks and in different countries. Celgosivir rapidly converted to
castanospermine (Cast) with mean peak and trough concentrations of 5727 ng/mL
(30.2 MUM) and 430 ng/mL (2.3 MUM), respectively and cleared with a half-life of
2.5 (+/- 0.6) hr. Mean viral log reduction between day 2 and 4 (VLR2-4) was
significantly greater in secondary dengue than primary dengue (p = 0.002). VLR2-4
did not correlate with drug AUC but showed a trend of greater response with
increasing Cmin. PK modeling identified dosing regimens predicted to achieve 2.4
to 4.5 times higher Cmin. than in the CELADEN trial for only 13% to 33% increase
in overall dose. A small, non-statistical trend towards better outcome on
platelet nadir and difference between maximum and minimum hematocrit was observed
in celgosivir-treated patients with secondary dengue infection. Optimization of
the dosing regimen and patient stratification may enhance the ability of a
clinical trial to demonstrate celgosivir activity in treating dengue fever based
on hematological endpoints. A new clinical trial with a revised dosing regimen is
slated to start in 2016 (NCT02569827). Furthermore celgosivir's potential value
for treatment of other flaviruses such as Zika virus should be investigated
urgently. TRIAL REGISTRATION: ClinicalTrials.gov NCT01619969.
PMID- 27509021
TI - Human Peripheral Blood Mononuclear Cell Function and Dendritic Cell
Differentiation Are Affected by Bisphenol-A Exposure.
AB - Environmental pollutants, including endocrine disruptor chemicals (EDCs),
interfere on human health, leading to hormonal, immune and metabolic
perturbations. Bisphenol-A (BPA), a main component of polycarbonate plastics, has
been receiving increased attention due to its worldwide distribution with a large
exposure. In humans, BPA, for its estrogenic activity, may have a role in
autoimmunity, inflammatory and allergic diseases. To this aim, we assessed the
effect of low BPA doses on functionality of human peripheral blood mononuclear
cells (PBMCs), and on in vitro differentiation of dendritic cells from monocytes
(mDCs). Fresh peripheral blood samples were obtained from 12 healthy adult
volunteers. PBMCs were left unstimulated or were activated with the mitogen
phytohemagglutinin (PHA) or the anti-CD3 and anti-CD28 antibodies and incubated
in presence or absence of BPA at 0.1 and 1nM concentrations. The immune
modulatory effect of BPA was assessed by evaluating the cell proliferation and
the levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-10
(IL-10) and interleukin-13 (IL-13) secreted by PBMCs. mDCs were differentiated
with IL-4 and GC-CSF with or without BPA and the expression of
differentiation/maturation markers (CD11c, CD1a, CD86, HLA-DR) was evaluated by
flow cytometry; furthermore, a panel of 27 different cytokines, growth factors
and chemokines were assayed in the mDC culture supernatants. PBMCs proliferation
significantly increased upon BPA exposure compared to BPA untreated cells. In
addition, a significant decrease in IL-10 secretion was observed in PBMCs
incubated with BPA, either in unstimulated or mitogen-stimulated cells, and at
both 0.1 and 1nM BPA concentrations. Similarly, IL-13 was reduced, mainly in
cells activated by antiCD3/CD28. By contrast, no significant changes in IFN-gamma
and IL-4 production were found in any condition assayed. Finally, BPA at 1nM
increased the density of dendritic cells expressing CD1a and concomitantly
decreased the expression of HLA-DR and CD86 activation markers. In conclusion, in
humans the exposure to BPA causes on PBMCs a significant modulation of
proliferative capacity and cytokine production, and on mDCs alteration in
differentiation and phenotype. These immune cell alterations suggest that low
dose chronic exposure to BPA could be involved in immune deregulation and
possibly in the increased susceptibility to develop inflammatory and autoimmune
diseases.
PMID- 27509022
TI - Background Colonic 18F-Fluoro-2-Deoxy-D-Glucose Uptake on Positron Emission
Tomography Is Associated with the Presence of Colorectal Adenoma.
AB - 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan is
used to evaluate various kinds of tumors. While most studies on PET findings of
the colon focus on the colonic uptake pattern, studies regarding background
colonic uptake on PET scan are rare. The purpose of this study was to identify
the association between the background colonic uptake and the presence of
colorectal adenoma (CRA), which is a frequent precancerous lesion. We
retrospectively reviewed the medical records of 241 patients with gynecologic
malignancy who had received PET or PET/computed tomography (CT) scan and
colonoscopy at the same period as a baseline evaluation. Background colonic 18F
FDG uptake was visually graded and the maximal standardized uptake values
(SUVmax) of 7 different bowel segments were averaged. In univariate analysis,
older age at diagnosis (>= 50 years, p = 0.034), overweight (BMI >= 23 kg/m2, p =
0.010), hypercholesterolemia (>= 200 mg/dL, p = 0.027), and high grade background
colonic uptake (p = 0.009) were positively associated with the prevalence of CRA.
By multiple logistic regression, high grade background colonic uptake was
independently predictive of CRA (odds ratio = 2.25, p = 0.021). The proportion of
CRA patients significantly increased as background colonic uptake grade increased
from 1 to 4 (trend p = 0.015). Out of the 138 patients who underwent PET/CT, the
proportion of CRA patients in the group with high SUVmax (> 2.25) was
significantly higher than in the low SUVmax group (27.5% vs. 11.6%, p = 0.031).
In conclusion, high grade of background colonic 18F-FDG uptake is significantly
associated with the prevalence of CRA.
PMID- 27509023
TI - The Small Mammal Sequence from the c. 76 - 72 ka Still Bay Levels at Blombos
Cave, South Africa - Taphonomic and Palaeoecological Implications for Human
Behaviour.
AB - The Still Bay, c. 76-72 ka, a prominent techno-tradition during the Middle Stone
Age of southern Africa, has yielded innovative technologies, symbolic material
culture, and shows evidence of expansion of hunting techniques and subsistence
strategies. In this paper we present the results of the first systematic,
taphonomic and palaeoenvironmental study of micromammals from the Still Bay
levels at Blombos Cave. Our taphonomic analysis indicates that the micromammals
were accumulated by avian predators occupying the cave. Post-depositional
processes affecting the micromammal assemblage include organic waste
decomposition and conditions associated with a limestone cave environment. The
palaeoenvironmental reconstruction shows that Marine Isotope Stage (MIS) 5a at
Blombos Cave had diverse micromammal communities occupying a variety of habitats
and with rainfall pattern equal to present. The transition from MIS 5a to 4 is
indicated by less diverse micromammal assemblages, increase in grassland and
scrub vegetation, shifts in seasonal precipitation, and a decline in shrubs
associated with fynbos. The onset of the glacial conditions associated with MIS 4
is visible in the micromammal assemblage. However humans occupying Blombos Cave
during this c. 5 ka period showed an ability to cope with changing environmental
conditions and were able to adapt and utilise a variety of available resources.
PMID- 27509024
TI - Exercise Activates p53 and Negatively Regulates IGF-1 Pathway in Epidermis within
a Skin Cancer Model.
AB - Exercise has been previously reported to lower cancer risk through reducing
circulating IGF-1 and IGF-1-dependent signaling in a mouse skin cancer model.
This study aims to investigate the underlying mechanisms by which exercise may
down-regulate the IGF-1 pathway via p53 and p53-related regulators in the skin
epidermis. Female SENCAR mice were pair-fed an AIN-93 diet with or without 10
week treadmill exercise at 20 m/min, 60 min/day and 5 days/week. Animals were
topically treated with TPA 2 hours before sacrifice and the target proteins in
the epidermis were analyzed by both immunohistochemistry and Western blot. Under
TPA or vehicle treatment, MDM2 expression was significantly reduced in exercised
mice when compared with sedentary control. Meanwhile, p53 was significantly
elevated. In addition, p53-transcriptioned proteins, i.e., p21, IGFBP-3, and
PTEN, increased in response to exercise. There was a synergy effect between
exercise and TPA on the decreased MDM2 and increased p53, but not p53
transcripted proteins. Taken together, exercise appeared to activate p53,
resulting in enhanced expression of p21, IGFBP-3, and PTEN that might induce a
negative regulation of IGF-1 pathway and thus contribute to the observed cancer
prevention by exercise in this skin cancer model.
PMID- 27509025
TI - Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage
IVa-b Nasopharyngeal Carcinoma.
AB - PURPOSE: The value of adding induction chemotherapy to chemoradiotherapy in
locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial,
yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We
aimed to assess the survival benefits of induction chemotherapy in stage IVa-b
NPC. PATIENTS AND METHODS: A total of 602 patients with stage IVa-b NPC treated
with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy
with or without induction chemotherapy were retrospectively analyzed. Overall
survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free
survival (DMFS) and progression-free survival (PFS) were evaluated using the
Kaplan-Meier method, log-rank test and Cox regression analysis. RESULTS: In
univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus
concurrent chemotherapy and 74.8% for concurrent chemotherapy alone,
corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to
concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year
DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P =
0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category,
chemotherapy strategy and clinical stage were associated with 5-year OS (P =
0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate
analysis, induction chemotherapy plus concurrent chemotherapy was an independent
favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and
DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction
chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P
= 0.008), but provided no significant benefit in stage IVb. CONCLUSIONS: In
patients with stage IVa-b NPC treated with IMRT, addition of induction
chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5
year DMFS. This study provides a basis for selection of high risk patients in
future clinical therapeutic trials.
PMID- 27509026
TI - Defining a BMI Cut-Off Point for the Iranian Population: The Shiraz Heart Study.
AB - In this study we evaluated and redefined the optimum body mass index (BMI) cut
off point for the Iranian population based on metabolic syndrome (MeS) risk
factors. We further evaluated BMI cut-off points with and without waist
circumference (WC) as a cofactor of risk and compared the differences. This study
is part of the largest surveillance programs conducted in Shiraz, Iran, termed
the Shiraz Heart study. Our study sample included subjects between the ages of 20
to 65 years old. After excluding pregnant women, those with missing data and
those with comorbid disease, a total of 12283 made up the study population. The
participants underwent a series of tests and evaluations by trained professionals
in accordance with WHO recommendations. Hypertension, abnormal fasting blood
sugar (FBS), triglyceride (TG) and high density lipoprotein cholesterol (HDL) (in
the context of the definition of metabolic syndrome) were prevalent among 32.4%,
27.6%, 42.1 and 44.2% of our participants, respectively. Women displayed higher
rates of overall obesity compared to men (based on the definition by the WHO as
higher than 30 kg/m2). Regarding MeS, 38.9% of our population had the all
symptoms of MeS which was more prevalent among women (41.5% vs. 36%). When
excluding WC in the definition of MeS, results showed that males tend to show a
higher rate of metabolic risk factors (19.2% vs. 15.6%). Results of multivariate
analysis showed that parallel to an increase in BMI, the odds ratio (OR) for
acquiring each component of the metabolic syndrome increased (OR = 1.178; CI:
1.166-1.190). By excluding WC, the previous OR decreased (OR = 1.105; CI: 1.093
1.118). Receiver Operating Characteristic (ROC) curve analysis showed that the
optimum BMI cut-off point for predicting metabolic syndrome was 26.1 kg/m2 and
26.2 kg/m2 [Accuracy (Acc) = 69% and 61%, respectively)] for males and females,
respectively. The overall BMI cut-off for both sexes was 26.2 kg/m2 (Acc = 65%)
with sensitivity and specificity of 69% and 62%, respectively. This cut-off had a
positive predictive value of 54% and a negative predictive value of 76%. When we
excluded waist circumference, the optimum BMI cut-off for acquiring metabolic
risk factors in males decreased to 25.7 kg/m2 (Acc = 67%) and increased for women
to 27.05 kg/m2 (Acc = 66%). Iranians are at higher risks of morbidity related to
metabolic factors at a lower BMI cut-off and prompt action and preventive health
policy are required to prevent and educate Iranians regarding diseases associated
with obesity.
PMID- 27509027
TI - Well-Being: An Important Concept for Psychotherapy and Psychiatric Neuroscience.
PMID- 27509028
TI - Social Interactions Receive Priority to Conscious Perception.
AB - Humans are social animals, constantly engaged with other people. The importance
of social thought and action is hard to overstate. However, is social information
so important that it actually determines which stimuli are promoted to conscious
experience and which stimuli are suppressed as invisible? To address this
question, we used a binocular rivalry paradigm, in which the two eyes receive
different action stimuli. In two experiments we measured the conscious percept of
rival actions and found that actions engaged in social interactions are granted
preferential access to visual awareness over non-interactive actions. Lastly, an
attentional task that presumably engaged the mentalizing system enhanced the
priority assigned to social interactions in reaching conscious perception. We
also found a positive correlation between human identification of interactive
activity and the promotion of socially-relevant information to visual awareness.
The present findings suggest that the visual system amplifies socially-relevant
sensory information and actively promotes it to consciousness, thereby
facilitating inferences about social interactions.
PMID- 27509029
TI - Impact of micro-environmental changes on respiratory tract infections with
intracellular bacteria.
AB - Community-acquired pneumonia is caused by intra- and extracellular bacteria, with
some of these bacteria also being linked to the pathogenesis of chronic lung
diseases, including asthma and chronic obstructive pulmonary disease. Chlamydia
pneumoniae is an obligate intracellular pathogen that is highly sensitive to
micro-environmental conditions controlling both pathogen growth and host immune
responses. The availability of nutrients, as well as changes in oxygen, pH and
interferon-gamma levels, have been shown to directly influence the chlamydial
life cycle and clearance. Although the lung has been traditionally regarded as a
sterile environment, sequencing approaches have enabled the identification of a
large number of bacteria in healthy and diseased lungs. The influence of the lung
microbiota on respiratory infections has not been extensively studied so far and
data on chlamydial infections are currently unavailable. In the present study, we
speculate on how lung microbiota might interfere with acute and chronic
infections by focusing exemplarily on the obligate intracellular C. pneumoniae.
Furthermore, we consider changes in the gut microbiota as an additional player in
the control of lung infections, especially in view the increasing evidence
suggesting the involvement of the gut microbiota in various immunological
processes throughout the human body.
PMID- 27509030
TI - Cross-Linking versus Non-Cross-Linking Aggregation of Gold Nanoparticles Induced
by DNA Hybridization: A Comparison of the Rapidity of Solution Color Change.
AB - Gold nanoparticles densely modified with single-stranded DNA (ssDNA-AuNPs) form
aggregates with cross-linker ssDNAs via duplex formation. Alternatively, the
ssDNA-AuNPs are spontaneously aggregated at high ionic strength in a non-cross
linking manner when complementary ssDNAs are added to form fully matched
duplexes. Both aggregation modes are accompanied by a red-to-purple color change,
which has been exploited in various bioassays. The current study compares the
rapidity of color change between the cross-linking and non-cross-linking
aggregation modes under identical conditions. When a small number of cross
linker/complementary DNAs are provided, the cross-linking mode exhibited more
rapid color change than the non-cross-linking mode. Conversely, with a large
number of the DNAs, the non-cross-linking aggregation occurred more rapidly than
the cross-linking counterpart. This finding allows one to select a more
appropriate aggregation mode for application of ssDNA-AuNPs to colorimetric
assays under given conditions.
PMID- 27509032
TI - Angiolipoma of the Breast: Multi-modality Imaging Findings.
PMID- 27509031
TI - Characterization of Laminin Binding Integrin Internalization in Prostate Cancer
Cells.
AB - Laminin binding integrins alpha6 (CD49f) and alpha3 (CD49c) are persistently but
differentially expressed in prostate cancer (PCa). Integrin internalization is an
important determinant of their cell surface expression and function. Using flow
cytometry, and first order kinetic modeling, we quantitated the intrinsic
internalization rates of integrin subunits in a single cycle of internalization.
In PCa cell line DU145, alpha6 integrin internalized with a rate constant
(kactual ) of 3.25 min-1 , threefold faster than alpha3 integrin (1.0 min-1 ),
1.5-fold faster than the vitronectin binding alphav integrin (CD51) (2.2 min-1 ),
and significantly slower than the unrelated transferrin receptor (CD71) (15 min-1
). Silencing of alpha3 integrin protein expression in DU145, PC3, and PC3B1 cells
resulted in up to a 1.71-fold increase in kactual for alpha6 integrin. The
internalized alpha6 integrin was targeted to early endosomes but not to lamp1
vesicles. Depletion of alpha3 integrin expression resulted in redistribution of
alpha6beta4 integrin to an observed cell-cell staining pattern that is consistent
with a suprabasal distribution observed in epidermis and early PIN lesions in
PCa. Depletion of alpha3 integrin increased cell migration by 1.8-fold, which was
dependent on alpha6beta1 integrin. Silencing of alpha6 integrin expression
however, had no significant effect on the kactual of alpha3 integrin or its
distribution in early endosomes. These results indicate that alpha3 and alpha6
integrins have significantly different internalization kinetics and that
coordination exists between them for internalization. J. Cell. Biochem. 118: 1038
1049, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27509033
TI - Mobilization of autologous and allogeneic peripheral blood stem cells for
transplantation in haematological malignancies using biosimilar G-CSF.
AB - BACKGROUND AND OBJECTIVES: Biosimilars of the granulocyte colony stimulating
factor (G-CSF) filgrastim were approved by the European Medicines Agency (EMA)
for registered indications of the originator G-CSF, including prevention and
treatment of neutropenia, as well as mobilization of peripheral blood stem cells
in 2008. Nevertheless, there is still an ongoing debate regarding the quality,
efficacy and safety of biosimilar G-CSF. MATERIALS AND METHODS: This article is a
meta-analysis of clinical studies on the use of biosimilar G-CSF for mobilization
and transplantation of haematopoietic stem cells as available in public
databases. All data sets were weighted for the number of patients and parameters
and then subjected to statistical meta-analysis employing the Mann-Whitney U-test
followed by the Hodges-Lehmann estimator to assess differences between biosimilar
and originator G-SCF. RESULTS: A total of 1892 individuals, mostly with
haematological malignancies but also including 351 healthy donors have been
successfully mobilized for autologous or allogeneic stem cell transplantation
using biosimilar G-CSF (Zarzio(TM) : 1239 individuals; Ratiograstim(TM)
/Tevagrastim(TM) : 653 individuals). A total of 740 patients with multiple
myeloma, 491 with non-Hodgkin's lymphoma (NHL), 150 with Hodgkin's lymphoma (HL)
and other diseases are included in this meta-analysis, as well as 161 siblings
and 190 volunteer unrelated donors. For biosimilar and originator G-CSF,
bioequivalence was observed for the yield of CD34+ stem cells as well as for the
engraftment of the transplants. CONCLUSION: Biosimilar G-CSF has equivalent
effects and safety as originator G-CSF.
PMID- 27509036
TI - Migrant and Refugee Patient Perspectives on Travel and Tuberculosis along the
Thailand-Myanmar Border: A Qualitative Study.
AB - BACKGROUND: The Thailand-Myanmar border separates two very different health
systems. The healthcare system in eastern Myanmar remains underdeveloped as a
result of decades of instability. Comparatively, Tak province, Thailand has more
healthcare resources. In this Thai border province government hospitals and non
governmental organizations provide tuberculosis (TB) treatment to migrants and
refugees. OBJECTIVES: Our overall study aimed to explore accessibility of TB
treatment, TB surveillance and health system responsiveness specific to migrant
and refugee populations in Tak province. In this paper, we focus on the
perspectives of migrant and refugee TB patients with respect to travel and
treatment in Tak province. METHODS: In 2014 we conducted focus group discussions
with 61 TB, Tuberculosis and Human Immunodeficiency Virus co-infection, and
multidrug-resistant TB patients in Tak province. We analyzed the data for content
and themes and documented individual travel trajectories. RESULTS AND DISCUSSION:
Migrants are travelling with active TB within the country and between Thailand
and Myanmar. Migrants primarily travelled to obtain treatment but two
participants reported travelling home to seek family care in Myanmar before
returning to Thailand for treatment. Travel, while expensive and arduous, is an
adaptive strategy that migrants use to access healthcare. CONCLUSIONS: Migrant's
need for travel points to larger difficulties associated with healthcare access
in the border region. Long distance travel with an infectious disease can be seen
as an indicator that local healthcare is not available or affordable. These
findings suggest that public health officials from both sides of the border
should discuss the factors that contribute to travel with active TB and explore
potential solutions to mitigate disease transmission in migrant populations.
PMID- 27509035
TI - A propensity score matching analysis of dasatinib and nilotinib as a frontline
therapy for patients with chronic myeloid leukemia in chronic phase.
AB - BACKGROUND: Both dasatinib and nilotinib are approved frontline therapy for
chronic myeloid leukemia in chronic phase (CML-CP) based on randomized trials
compared with imatinib. However, no head-to-head comparison of dasatinib and
nilotinib has been conducted in patients with newly diagnosed CML-CP. METHODS:
The authors conducted a propensity score (PS) matched comparison of patients with
CML-CP who received frontline therapy with either dasatinib (N = 102) or
nilotinib (N = 104) under the respective phase 2 trials conducted in parallel.
RESULTS: PS matching resulted in 87 patients from each trial being matched for
pretreatment characteristics. The 3-month BCR-ABL1/ABL1 ratio <10% rate was 93%
with dasatinib and 94% with nilotinib (P = .25); the rates of major molecular
response at 12 months were 77% and 85%, respectively (P = .13); and the rates of
molecular response with 4.5-log reduction in the ratio at 36 months were 66% and
64%, respectively (P = .96). All other clinically relevant responses were similar
between the 2 treatment cohorts. The 3-year probability of event-free survival
was 89% among the patients who received dasatinib and 87% among those who
received nilotinib (P = .99), and the corresponding 3-year overall survival
probabilities were 99% and 93%, respectively (P = .95). No statistical difference
was observed between the dasatinib and nilotinib groups in any of the other
survival endpoints. The treatment discontinuation rate also was similar between
the 2 cohorts (dasatinib group, 18%; nilotinib group, 19%; P = .82). CONCLUSIONS:
In a PS-matched cohort of patients with newly diagnosed CML-CP, dasatinib and
nilotinib offer similar response and survival outcomes. Both drugs can be
considered reasonable standard-of-care options as first-line therapy for patients
with CML-CP. Cancer 2016;122:3336-3343. (c) 2016 American Cancer Society.
PMID- 27509038
TI - Surgical Management of Pediatric Developmental Dysplasia of the Hip.
AB - In pediatric patients with developmental dysplasia of the hip with late
presentation or failure of nonsurgical treatment, surgical management is
indicated. The goal of surgery is to obtain a stable reduction to promote
development of the femoral head and acetabulum while avoiding osteonecrosis of
the femoral head and the need for further surgery. Treatment is related to the
age of the patient and the degree of soft-tissue contracture or bony deformity
present. As a general rule, in children aged <12 months, closed reduction and
spica casting is preferred. Children aged 12 to 18 months may require open
reduction, which can be performed safely through a medial or anterior approach.
In children aged 18 months to 3 years, residual bony deformity can be corrected
with a femoral or pelvic osteotomy in addition to open reduction. In children
with complex deformity or in children aged >3 years, both pelvic and femoral
osteotomies are commonly required to stabilize an open reduction.
PMID- 27509037
TI - Novel Ordered Stepped-Wedge Cluster Trial Designs for Detecting Ebola Vaccine
Efficacy Using a Spatially Structured Mathematical Model.
AB - BACKGROUND: During the 2014 Ebola virus disease (EVD) outbreak, policy-makers
were confronted with difficult decisions on how best to test the efficacy of EVD
vaccines. On one hand, many were reluctant to withhold a vaccine that might
prevent a fatal disease from study participants randomized to a control arm. On
the other, regulatory bodies called for rigorous placebo-controlled trials to
permit direct measurement of vaccine efficacy prior to approval of the products.
A stepped-wedge cluster study (SWCT) was proposed as an alternative to a more
traditional randomized controlled vaccine trial to address these concerns. Here,
we propose novel "ordered stepped-wedge cluster trial" (OSWCT) designs to further
mitigate tradeoffs between ethical concerns, logistics, and statistical rigor.
METHODOLOGY/PRINCIPAL FINDINGS: We constructed a spatially structured
mathematical model of the EVD outbreak in Sierra Leone. We used the output of
this model to simulate and compare a series of stepped-wedge cluster vaccine
studies. Our model reproduced the observed order of first case occurrence within
districts of Sierra Leone. Depending on the infection risk within the trial
population and the trial start dates, the statistical power to detect a vaccine
efficacy of 90% varied from 14% to 32% for standard SWCT, and from 67% to 91% for
OSWCTs for an alpha error of 5%. The model's projection of first case occurrence
was robust to changes in disease natural history parameters.
CONCLUSIONS/SIGNIFICANCE: Ordering clusters in a step-wedge trial based on the
cluster's underlying risk of infection as predicted by a spatial model can
increase the statistical power of a SWCT. In the event of another hemorrhagic
fever outbreak, implementation of our proposed OSWCT designs could improve
statistical power when a step-wedge study is desirable based on either ethical
concerns or logistical constraints.
PMID- 27509039
TI - A Novel Algorithm for Isolated Weber B Ankle Fractures: A Retrospective Review of
51 Nonsurgically Treated Patients.
AB - INTRODUCTION: Stability of isolated Weber B ankle fractures can be difficult to
determine. Using weight-bearing radiographs, a reliable method to determine the
stability of isolated Weber B ankle fractures is described. METHODS: A
retrospective review of prospectively gathered data was performed. Weber B ankle
fractures were defined as stable when having a medial clear space (MCS) of <7 mm
on initial gravity stress radiographs and a normal mortise relationship on weight
bearing radiographs. Fifty-one patients meeting these criteria were treated
nonsurgically with protected weight bearing and serial radiography for 1 year.
RESULTS: Average functional score results were: American Orthopaedic Foot and
Ankle Society Hindfoot, 93.2; Foot and Ankle Ability Measure for Activities of
Daily Living, 93.2; Olerud-Molander Ankle Score, 91.0; and visual analog scale
pain score, 0.57. Despite a mean gravity stress MCS of 4.42 mm, no patient
demonstrated subsequent MCS widening. Mean MCS on 1-year follow-up weight-bearing
radiographs was 2.64 mm. CONCLUSION: Weight-bearing ankle radiographs are
predictive of stability in isolated Weber B ankle fractures. Gravity stress
radiographs using traditional measurement criteria may overestimate instability
in these injuries. Nonsurgical treatment with protected weight bearing shows good
early outcomes. LEVEL OF EVIDENCE: IV.
PMID- 27509040
TI - Fetal Heart Rate during in Utero Myelomeningocele Repair: Effect of Anesthesia
and Analgesia.
PMID- 27509041
TI - MMpI: A WideRange of Available Compounds of Matrix Metalloproteinase Inhibitors.
AB - Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases
involved in the regulation of the extracellular signaling and structural matrix
environment of cells and tissues. MMPs are considered as promising targets for
the treatment of many diseases. Therefore, creation of database on the inhibitors
of MMP would definitely accelerate the research activities in this area due to
its implication in above-mentioned diseases and associated limitations in the
first and second generation inhibitors. In this communication, we report the
development of a new MMpI database which provides resourceful information for all
researchers working in this field. It is a web-accessible, unique resource that
contains detailed information on the inhibitors of MMP including small molecules,
peptides and MMP Drug Leads. The database contains entries of ~3000 inhibitors
including ~72 MMP Drug Leads and ~73 peptide based inhibitors. This database
provides the detailed molecular and structural details which are necessary for
the drug discovery and development. The MMpI database contains physical
properties, 2D and 3D structures (mol2 and pdb format files) of inhibitors of
MMP. Other data fields are hyperlinked to PubChem, ChEMBL, BindingDB, DrugBank,
PDB, MEROPS and PubMed. The database has extensive searching facility with MMpI
ID, IUPAC name, chemical structure and with the title of research article. The
MMP inhibitors provided in MMpI database are optimized using Python-based
Hierarchical Environment for Integrated Xtallography (Phenix) software. MMpI
Database is unique and it is the only public database that contains and provides
the complete information on the inhibitors of MMP. Database URL:
http://clri.res.in/subramanian/databases/mmpi/index.php.
PMID- 27509042
TI - DNA Barcoding the Heliothinae (Lepidoptera: Noctuidae) of Australia and Utility
of DNA Barcodes for Pest Identification in Helicoverpa and Relatives.
AB - Helicoverpa and Heliothis species include some of the world's most significant
crop pests, causing billions of dollars of losses globally. As such, a number are
regulated quarantine species. For quarantine agencies, the most crucial issue is
distinguishing native species from exotics, yet even this task is often not
feasible because of poorly known local faunas and the difficulties of identifying
closely related species, especially the immature stages. DNA barcoding is a
scalable molecular diagnostic method that could provide the solution to this
problem, however there has been no large-scale test of the efficacy of DNA
barcodes for identifying the Heliothinae of any region of the world to date. This
study fills that gap by DNA barcoding the entire heliothine moth fauna of
Australia, bar one rare species, and comparing results with existing public
domain resources. We find that DNA barcodes provide robust discrimination of all
of the major pest species sampled, but poor discrimination of Australian
Heliocheilus species, and we discuss ways to improve the use of DNA barcodes for
identification of pests.
PMID- 27509043
TI - Reinforcer Pathology: The Behavioral Economics of Abuse Liability Testing.
AB - Understanding the abuse liability of novel drugs is critical to understanding the
risk these new compounds pose to society. Behavioral economics, the integration
of psychology and economics, can be used to predict abuse liability of novel
substances. Here, we describe the behavioral economic concept of reinforcer
pathology and how it may predict the use of novel drugs in existing drug-users
and initiation of use in the drug-naive.
PMID- 27509044
TI - Creating a More Diverse Midwifery Workforce in the United States: A Historical
Reflection.
AB - INTRODUCTION: As nurse-midwifery practice expanded beyond areas surrounding early
nurse-midwifery education programs, leaders in the profession wanted to establish
a strong diverse, inclusive professional organization, a necessary step in
creating a diverse workforce (defined here as open to nurse-midwives of all
colors, ethnicities, and national origins) that would maintain standards, provide
continuing education, and facilitate communication among nurse-midwives. This
research presents historical context and organizational factors supporting and
limiting development of a workforce reflective of communities served by nurse
midwives. METHODS: Searches in the National Library of Medicine Historical
Collection, American College of Nurse-Midwives (ACNM) Collections, and the
Rockefeller Archives Center, as well as recorded interview data, provided primary
sources for analysis. Secondary sources include research and opinions in
scholarly publications including journals and books released from 1930 to the
present. RESULTS: Nurse-midwifery leaders developed relationships with well
respected philanthropists, as well as maternal and child health administrators in
state departments of health and the US Children's Bureau, to implement
initiatives to recruit and retain midwives of color. Continued interest in the
goal of inclusion, work of midwives of color, and commitment to creating a
diverse workforce led to the creation of the standing ACNM Midwives of Color
Committee in 1990 and the Diversity and Inclusion Task Force, which released its
report, "Shifting the Frame: A Report on Diversity and Inclusion in the American
College of Nurse-Midwives,"1 in June 2015. DISCUSSION: Over the past 60 years,
ACNM leadership and midwives of color have continued to explore new and effective
means to create a workforce that reflects the communities in which nurse-midwives
practice.
PMID- 27509045
TI - Redox-Sensitive and Intrinsically Fluorescent Photoclick Hyaluronic Acid Nanogels
for Traceable and Targeted Delivery of Cytochrome c to Breast Tumor in Mice.
AB - In spite of their high specificity and potency, few protein therapeutics are
applied in clinical cancer therapy owing to a lack of safe and efficacious
delivery systems. Here, we report that redox-sensitive and intrinsically
fluorescent photoclick hyaluronic acid nanogels (HA-NGs) show highly efficient
loading and breast tumor-targeted delivery of cytochrome c (CC). HA-NGs were
obtained from hyaluronic acid-graft-oligo(ethylene glycol)-tetrazole (HA-OEG-Tet)
via inverse nanoprecipitation and catalyst-free photoclick cross-linking with l
cystine dimethacrylamide (MA-Cys-MA). HA-NGs exhibited a superb CC loading
content of up to 40.6 wt %, intrinsic fluorescence (lambdaem = 510 nm), and a
small size of ca. 170 nm. Notably, CC-loaded nanogels (CC-NGs) showed a fast
glutathione-responsive protein release behavior. Importantly, released CC
maintained its bioactivity. MTT assays revealed that CC-NGs were highly potent
with a low IC50 of 3.07 MUM to CD44+ MCF-7 human breast tumor cells. Confocal
microscopy observed efficient and selective internalization of fluorescent HA-NGs
into MCF-7 cells. Interestingly, HA-NGs exhibited also effective breast tumor
penetration. The therapeutic results demonstrated that CC-NGs effectively
inhibited the growth of MCF-7 breast tumor xenografts at a particularly low dose
of 80 or 160 nmol CC equiv./kg. Moreover, CC-NGs did not cause any change in mice
body weight, corroborating their low systemic side effects. Redox-sensitive and
intrinsically fluorescent photoclick hyaluronic acid nanogels have appeared as a
"smart" protein delivery nanoplatform enabling safe, efficacious, traceable, and
targeted cancer protein therapy in vivo.
PMID- 27509046
TI - Differences in Patient Outcomes of Prevalence, Interval, and Screen-Detected Lung
Cancers in the CT Arm of the National Lung Screening Trial.
AB - Lung cancer screening identifies cancers with heterogeneous behaviors. Some lung
cancers will be identified among patients who had prior negative CT screens and
upon follow-up scans develop a de novo nodule that was determined to be
cancerous. Other lung cancers will be identified among patients who had one or
more prior stable positive scans that were not determined to be lung cancer
(indeterminate pulmonary nodules), but in follow-up scans was diagnosed with an
incidence lung cancer. Using data from the CT arm of the National Lung Screening
Trial, this analysis investigated differences in patient characteristics and
survival endpoints between prevalence-, interval-, and screen-detected lung
cancers, characterized based on sequence of screening results. Lung cancers
immediately following a positive baseline (T0), and prior to the T1 screen,
formed the prevalence cohort. Interval cancers were diagnosed following a
negative screen at any time point prior to the next screening round. Two cohorts
of screen-detected lung cancers (SDLC) were identified that had a baseline
positive screen that was that was not determined to be lung cancer (i.e., an
indeterminate pulmonary nodule), but in follow-up scans was diagnosed with an
incidence lung cancer 12 (SDLC1) or 24 (SDLC2) months later. Two other incidence
cohorts had screen-detected lung cancers that had baseline negative screen and
upon follow-up scans developed a de novo nodule determined to be cancerous at 12
(SDLC3) or 24 (SDLC4) months later. Differences in patient characteristics,
progression-free survival (PFS), and overall survival (OS) were assessed. The
lung cancer-specific death rate was higher for SDLC3/SDLC4 compared to
SDLC1/SDLC2 lung cancers (136.6/1,000 person-years vs. 71.3/1,000 person-years, P
< 0.001). Moreover, PFS and OS were significantly lower for SDLC3/SDLC4 compared
to SDLC1/SDLC2 (P < 0.004; P < 0.002, respectively). The findings were consistent
when stratified by stage and histology. Multivariable Cox proportional models
revealed that the SDLC3/SDLC4 case groups were associated with significantly
poorer PFS (HR = 1.89; 95% CI 1.31-2.74) and OS (HR = 1.80; 95% CI 1.21-2.67)
compared to SDLC1/SDLC2 lung cancers (HR = 1.00). Lung cancer patients who
develop a de novo nodule that determined to be cancerous (i.e., at least one
negative CT screen prior to cancer diagnosis) had poorer survival outcomes
compared to patients who had at least one positive screen prior to cancer
diagnosis. As such, the observation that de novo screen-detected are associated
with poorer survival could be attributed to faster growing, more aggressive
cancers that arose from a lung environment previously lacking focal
abnormalities.
PMID- 27509047
TI - Curcumin cross-linked collagen aerogels with controlled anti-proteolytic and pro
angiogenic efficacy.
AB - This paper elucidates the development of a curcumin cross-linked collagen aerogel
system with controlled anti-proteolytic activity and pro-angiogenic efficacy. The
results of this study showed that in situ cross-linking of curcumin with collagen
leads to the development of aerogels with enhanced physical and mechanical
properties. The integrity of collagen after cross-linking with curcumin was
studied via FTIR spectroscopy. The results confirmed that the cross-linking with
curcumin did not induce any structural changes in the collagen. The curcumin
cross-linked collagen aerogels exhibited potent anti-proteolytic and anti
microbial activity. Scanning electron and atomic force microscopic analysis of
curcumin cross-linked collagen aerogels showed a 3D microstructure that enhanced
the adhesion and proliferation of cells. The highly organized geometry of
collagen-curcumin aerogels enhanced the permeability and water-retaining ability
required for the diffusion of nutrients that aid cellular growth. The pro
angiogenic properties of collagen-curcumin aerogels were ascribed to the
cumulative effect of the nutraceutical and the collagen molecule, which augmented
the restoration of damaged tissue. Further, these aerogels exhibited controlled
anti-proteolytic activity, which makes them suitable 3D scaffolds for biomedical
applications. This study provides scope for the development of biocompatible and
bioresorbable collagen aerogel systems that use a nutraceutical as a cross-linker
for biomedical applications.
PMID- 27509049
TI - Genetic Diversity and Population Structure of Cowpea (Vigna unguiculata L. Walp).
AB - The genetic diversity of cowpea was analyzed, and the population structure was
estimated in a diverse set of 768 cultivated cowpea genotypes from the USDA GRIN
cowpea collection, originally collected from 56 countries. Genotyping by
sequencing was used to discover single nucleotide polymorphism (SNP) in cowpea
and the identified SNP alleles were used to estimate the level of genetic
diversity, population structure, and phylogenetic relationships. The aim of this
study was to detect the gene pool structure of cowpea and to determine its
relationship between different regions and countries. Based on the model-based
ancestry analysis, the phylogenetic tree, and the principal component analysis,
three well-differentiated genetic populations were postulated from 768 worldwide
cowpea genotypes. According to the phylogenetic analyses between each individual,
region, and country, we may trace the accession from off-original, back to the
two candidate original areas (West and East of Africa) to predict the migration
and domestication history during the cowpea dispersal and development. To our
knowledge, this is the first report of the analysis of the genetic variation and
relationship between globally cultivated cowpea genotypes. The results will help
curators, researchers, and breeders to understand, utilize, conserve, and manage
the collection for more efficient contribution to international cowpea research.
PMID- 27509048
TI - Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after
Infection Are Associated with More Rapid HIV/SIV Disease Onset.
AB - Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were
described as an independent marker of rapid disease onset, more robust than peak
viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which
include major HIV-target cells, raising the question if it promotes the
establishment of viral reservoirs. We analyzed data from four cohorts of HIV+
patients, allowing us to study IP-10 levels before infection (Amsterdam cohort),
as well as during controlled and uncontrolled viremia (ANRS cohorts). We also
addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood
viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10
levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection.
During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell
associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10
levels tended to differ between HIV controllers with detectable and undetectable
viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV
DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine
than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and
round CD68neg cells as well as to macrophages. Blood IP-10 response negatively
correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3
expression was higher on memory CD4+ T cells than any other immune cells. CD4 T
cells from chronically infected animals expressed extremely high levels of intra
cellular CXCR3 suggesting internalization after ligand recognition. Elevated
systemic IP-10 levels before infection associated with rapid disease progression.
Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was
regionalized in the intestine during early SIV infection and CD68+ and CD68neg
haematopoietic cells in the small intestine appeared to be the major source of IP
10.
PMID- 27509050
TI - The Chronic Effects of Low- and High-Intensity Resistance Training on Muscular
Fitness in Adolescents.
AB - To compare the effects of high-load, low-repetition maximum (LRM) and low-load,
high-repetition maximum (HRM) resistance training regimens on muscular fitness in
untrained adolescents. Forty-five untrained adolescents of both sexes (13.7+/-0.8
years; 161.3+/-7.5 cm, 56.8+/-13.4 kg) were randomly assigned into one of three
groups: 1) LRM (n = 17): volunteers performed three sets of 4-6-repetition
maximum (RM); 2) HRM (n = 16): volunteers performed three sets of 12-15 RM; and
3) control (CON, n = 12). Training was performed two times a week for 9 weeks.
After training, there were significant increases in 1 RM chest press (LRM = 14.8%
and HRM = 14.2%, p<0.05) and squat (LRM = 26.4% and HRM = 25.7%, p<0.05), with no
differences between the LRM and HRM groups (p>0.05). Additionally, muscular
endurance increased significantly for the chest press (LRM = 14.5% and HRM =
21.8%, p<0.05) and squat test (LRM = 31.4% and HRM = 32.4%, p<0.05) following
resistance training, with no difference between the LRM and HRM groups (p>0.05).
These results suggest that both high-load, low-repetition and moderate-load, high
repetition resistance training can be prescribed to improve muscular fitness in
untrained adolescents.
PMID- 27509051
TI - Clostridium difficile Infections in Medical Intensive Care Units of a Medical
Center in Southern Taiwan: Variable Seasonality and Disease Severity.
AB - Critical patients are susceptible to Clostridium difficile infections (CDIs),
which cause significant morbidity and mortality in the hospital. In Taiwan, the
epidemiology of CDI in intensive care units (ICUs) is not well understood. This
study was aimed to describe the incidence and the characteristics of CDI in the
ICUs of a medical center in southern Taiwan. Adult patients with diarrhea but
without colostomy/colectomy or laxative use were enrolled. Stool samples were
collected with or without 5 ml alcohol and were plated on cycloserine-cefoxitin
fructose agar. C. difficile identification was confirmed by polymerase chain
reaction. There were 1,551 patients admitted to ICUs, 1,488 screened, and 145
with diarrhea. A total of 75 patients were excluded due either to laxative use, a
lack of stool samples, or refusal. Overall, 70 patients were included, and 14
(20%) were diagnosed with CDI, with an incidence of 8.8 cases per 10,000 patient
days. The incidence of CDI was found to be highest in March 2013 and lowest in
the last quarter of 2013. The cases were categorized as the following: 5 severe,
complicated, 5 severe, and 4 mild or moderate diseases. Among the 14 cases of
CDI, the median patient age was 74 (range: 47-94) years, and the median time from
admission to diarrhea onset was 16.5 (4-53) days. Eight cases received
antimicrobial treatment (primarily metronidazole), and the time to diarrheal
resolution was 11.5 days. Though 6 cases were left untreated, no patients died of
CDI. The in-hospital mortality of CDI cases was 50%, similar to that of patients
without CDI (46.4%; P = 1.0). We concluded that the overall incidence of CDI in
our medical ICUs was low and there were variable seasonal incidences and disease
severities of CDI.
PMID- 27509053
TI - Interferon stimulated genes and innate immune activation following infection with
hepatitis B and C viruses.
AB - Although not directly cytopathic, hepatitis B and C viruses (HBV and HCV) are
responsible for millions of deaths per year, and the aging patient population
presents a severe public health challenge. Most cases of acute HCV become
chronic, but treatment has become increasingly successful following the
development of direct acting antiviral agents. Conversely, most cases of acute
HBV are cleared in the pre-symptomatic stage and do not become chronic, but
treatment options for chronic HBV are limited and rarely result in clearance.
Despite these differences, interferon is partially effective against both viruses
and has long been used in therapy. Newer treatments have largely moved away from
interferon in favor of more targeted approaches, but interferon signaling remains
the body's first line of defense against viruses. The recent discovery of type
III interferon and IFNL4 has yielded new insights into the mechanism of ISG
activation and revealed potential new therapeutic targets. J. Med. Virol. 89:388
396, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27509052
TI - Modelling the Structure and Dynamics of Biological Pathways.
AB - There is a need for formalised diagrams that both summarise current biological
pathway knowledge and support modelling approaches that explain and predict their
behaviour. Here, we present a new, freely available modelling framework that
includes a biologist-friendly pathway modelling language (mEPN), a simple but
sophisticated method to support model parameterisation using available biological
information; a stochastic flow algorithm that simulates the dynamics of pathway
activity; and a 3-D visualisation engine that aids understanding of the
complexities of a system's dynamics. We present example pathway models that
illustrate of the power of approach to depict a diverse range of systems.
PMID- 27509054
TI - MALDI imaging reveals NCOA7 as a potential biomarker in oral squamous cell
carcinoma arising from oral submucous fibrosis.
AB - Oral squamous cell carcinoma (OSCC) ranks among the most common cancer worldwide,
and is associated with severe morbidity and high mortality. Oral submucous
fibrosis (OSF), characterized by fibrosis of the mucosa of the upper digestive
tract, is a pre-malignant lesion, but the molecular mechanisms underlying this
malignant transformation remains to be elucidated. In this study, matrix-assisted
laser desorption ionization imaging mass spectrometry (MALDI-IMS)-based proteomic
strategy was employed to profile the differentially expressed peptides/proteins
between OSCC tissues and the corresponding adjacent non-cancerous OSF tissues.
Sixty-five unique peptide peaks and nine proteins were identified with altered
expression levels. Of them, expression of NCOA7 was found to be up-regulated in
OSCC tissues by immunohistochemistry staining and western blotting, and
correlated with a pan of clinicopathologic parameters, including lesion site,
tumor differentiation status and lymph node metastasis. Further, we show that
overexpression of NCOA7 promotes OSCC cell proliferation in either in vitro or in
vivo models. Mechanistic study demonstrates that NCOA7 induces OSCC cell
proliferation probably by activating aryl hydrocarbon receptor (AHR). The present
study suggests that NCOA7 is a potential biomarker for early diagnosis of OSF
malignant transformation, and leads to a better understanding of the molecular
mechanisms responsible for OSCC development.
PMID- 27509055
TI - Crosstalk between the mitochondrial fission protein, Drp1, and the cell cycle is
identified across various cancer types and can impact survival of epithelial
ovarian cancer patients.
AB - Mitochondrial metabolic reprogramming is a hallmark of tumorigenesis. Although
mitochondrial function can impact cell cycle regulation it has been an
understudied area in cancer research. Our study highlights a specific involvement
of mitochondria in cell cycle regulation across cancer types. The mitochondrial
fission process, which is regulated at the core by Drp1, impacts various cellular
functions. Drp1 has been implicated in various cancer types with no common
mechanism reported. Our Drp1-directed large-scale analyses of the publically
available cancer genomes reveal a robust correlation of Drp1 with cell-cycle
genes in 29 of the 31 cancer types examined. Hypothesis driven investigation on
epithelial ovarian cancer (EOC) revealed that Drp1 co-expresses specifically with
the cell-cycle module responsible for mitotic transition. Repression of Drp1 in
EOC cells can specifically attenuate mitotic transition, establishing a potential
casual role of Drp1 in mitotic transition. Interestingly, Drp1-Cell-Cycle co
expression module is specifically detected in primary epithelial ovarian tumors
that robustly responded to chemotherapy, suggesting that Drp1 driven mitosis may
underlie chemo-sensitivity of the primary tumors. Analyses of matched primary and
relapsed EOC samples revealed a Drp1-based-gene-expression-signature that could
identify patients with poor survival probabilities from their primary tumors. Our
results imply that around 60% of platinum-sensitive EOC patients undergoing
relapse show poor survival, potentially due to further activation of a
mitochondria driven cell-cycle regime in their recurrent disease. We speculate
that this patient group could possibly benefit from mitochondria directed
therapies that are being currently evaluated at various levels, thus enabling
targeted or personalized therapy based cancer management.
PMID- 27509056
TI - XB130 is overexpressed in prostate cancer and involved in cell growth and
invasion.
AB - XB130 is a cytosolic adaptor protein involved in various physiological processes
and oncogenesis of certain malignancies, but its role in the development of
prostate cancer remains unclear. In current study, we examined XB130 expression
in prostate cancer tissues and found that XB130 expression was remarkably
increased in prostate cancer tissues and significantly correlated with increased
prostate specific antigen (PSA), free PSA (f-PSA), prostatic acid phosphatase
(PAP) and T classification. Patients with highly expressed XB130 had
significantly decreased survival, which suggested XB130 as a possible prognostic
indicator for prostate cancer. In vitro experiments showed that reduced XB130
expression restrained tumor growth both in vitro and in vivo. Furthermore, XB130
knockdown hindered transition of G1 to S phase in prostate cancer cell line DU145
and LNCap, which might contribute to the inhibition of cellular proliferation.
Results from transwell assay demonstrated that downregulation of XB130 may
attenuate invasion and metastasis of prostate cancer. Semiquantitative analysis
of Western blot suggested that decreased XB130 expression was accompanied by
diminished Akt signaling and EMT process. Thus, above observations suggest that
XB130 may be a novel molecular marker and potent therapeutic target for prostate
cancer.
PMID- 27509058
TI - NLRP3 inflammasome activation is involved in Ang II-induced kidney damage via
mitochondrial dysfunction.
AB - Growing evidence has shown that NLRP3 inflammasome activation promotes the
development of tubularinterstitial inflammation and progression of renal injury.
We previously found that mitochondrial dysfunction is a critical determinant for
the activation of NLRP3 inflammasome in albumin-overload rats. Angiotensin (Ang)
II plays an important role in mitochondrial homeostasis. Here, we investigated
the role of Ang II in NLRP3 inflammasome activation and the involvement of
mitochondrial dysfunction in this process. In vitro, Ang II triggered NLRP3
inflammasome activation in a dose- and time-dependent manner, and this effect is
mediated by AT1 receptor rather than AT2 receptor. MitoTEMPO, a mitochondrial
targeted antioxidant, attenuated Ang II induced mitochondrial reactive oxygen
species (mROS) production and NLRP3 inflammation activation. Following chronic
Ang II infusion for 28 days, we observed remarkable tubular epithelial cells
(TECs) injury, mitochondrial damage, and albuminuria in WT mice. However, these
abnormalities were significantly attenuated in AT1 receptor KO mice. Then, we
examined the role of mitochondria in Ang II-infused mice with or without
mitoTEMPO treatment. As expected, Ang II-induced mitochondrial dysfunction and
NLRP3 inflammasome activation was markedly inhibited by mitoTEMPO. Notably, NLRP3
deletion signally protected TECs from Ang II-triggered mitochondrial dysfunction
and NLRP3 inflammasome activation. Taken together, these data demonstrate that
Ang II induces NLRP3 inflammasome activation in TECs which is mediated by
mitochondrial dysfunction.
PMID- 27509057
TI - Increased Rab35 expression is a potential biomarker and implicated in the
pathogenesis of Parkinson's disease.
AB - Parkinson's disease (PD) is the second common neurodegenerative disease.
Identification of biomarkers for early diagnosis and prediction of disease
progression is important. The present comparative proteomic study of serum
samples using two-dimensional fluorescence differential gel electrophoresis
followed by ELISA confirmation demonstrated that protein expression of Rab35 was
increased in PD patients compared with matched control subjects and other
parkinsonian disorders, progressive supranuclear palsy (PSP) and multiple system
atrophy (MSA). The serum level of Rab35 was significantly correlated with the age
at onset of PD. The median age of onset in patients with higher Rab35 serum level
was 5 years younger than those with lower Rab35 serum level. There was a positive
correlation between the Rab35 level and disease duration of PD. Moreover, the
protein expression of Rab35 was increased in the substantia nigra but not in the
striatum of mouse models of PD, including MPTP-treated mice, rotenone-treated
mice, (R1441C) LRRK2 or (G2019S) LRRK2 transgenic mice. Furthermore,
overexpression of Rab35 increased the aggregation and secretion of mutant A53T
alpha-synuclein in dopaminergic SH-SY5Y cells. Co-expression of Rab35 with wild
type or A53T alpha-synuclein in SH-SY5Y cells deteriorated cell death. Our
results suggest that Rab35 is potentially useful in the differential diagnosis of
parkinsonian disorders and is implicated in the pathogenesis of PD.
PMID- 27509059
TI - Systematic identification of immunodominant CD4+ T cell responses to HpaA in
Helicobacter pylori infected individuals.
AB - In mice, antigen-specific CD4+ T cell response is indispensible for the
protective immunity against Helicobacter pylori (H. pylori). It has been
demonstrated that neuraminyllactose-binding hemagglutinin (HpaA) immunization
protected mice from H. pylori infection in a CD4+ T cell dependent manner.
However, much remains unclear concerning the human CD4+ T cell responses to HpaA.
We conducted a systematic study here to explore the immunodominant, HpaA-specific
CD4+ T cell responses in H. pylori infected individuals. We found that HpaA
specific CD4+ T cell responses varied remarkably in their magnitude and had broad
epitope-specificity. Importantly, the main responses focused on two regions:
HpaA76-105 and HpaA130-159. The HLA-DRB1*0901 restricted HpaA142-159 specific
CD4+ T cell response was the most immunodominant response at a population level.
The immunodominant epitope HpaA142-159 was naturally presented and highly
conserved. We also demonstrated that it was not the broad peptide specificity,
but the strength of HpaA specific CD4+ T cell responses associated with gastric
diseases potentially caused by H. pylori infection. Such investigation will aid
development of novel vaccines against H. pylori infection.
PMID- 27509060
TI - Immortalization of human AE pre-leukemia cells by hTERT allows leukemic
transformation.
AB - Human CD34+ hematopoietic stem and progenitor cells (HSPC) expressing fusion
protein AML1-ETO (AE), generated by the t(8;21)(q22;q22) rearrangement, manifest
enhanced self-renewal and dysregulated differentiation without leukemic
transformation, representing a pre-leukemia stage. Enabling replicative
immortalization via telomerase reactivation is a crucial step in cancer
development. However, AE expression alone is not sufficient to maintain high
telomerase activity to immortalize human HSPC cells, which may hamper
transformation. Here, we investigated the cooperativity of telomerase reverse
transcriptase (hTERT), the catalytic subunit of telomerase, and AE in disease
progression. Enforced expression of hTERT immortalized human AE pre-leukemia
cells in a telomere-lengthening independent manner, and improved the pre-leukemia
stem cell function by enhancing cell proliferation and survival. AE-hTERT cells
retained cytokine dependency and multi-lineage differentiation potential similar
to parental AE clones. Over the short-term, AE-hTERT cells did not show features
of stepwise transformation, with no leukemogenecity evident upon initial
injection into immunodeficient mice. Strikingly, after extended culture, we
observed full transformation of one AE-hTERT clone, which recapitulated the
disease evolution process in patients and emphasizes the importance of acquiring
cooperating mutations in t(8;21) AML leukemogenesis. In summary, achieving
unlimited proliferative potential via hTERT activation, and thereby allowing for
acquisition of additional mutations, is a critical link for transition from pre
leukemia to overt disease in human cells. AE-hTERT cells represent a tractable
model to study cooperating genetic lesions important for t(8;21) AML disease
progression.
PMID- 27509061
TI - Weekly versus three weeks chemotherapy for advanced ovarian cancer: a meta
analysis.
AB - AIM: Three weeks paclitaxel and carboplatin has been considered the standard of
care for primary treatment of ovarian cancer (OC). Whether weekly therapy will
further improve the clinical outcomes or not is still unclear. We conducted a
meta-analysis to compare the two regimens. METHOD: Articles were selected with a
systematic approach, using PubMed databases. Trials concerning comparison between
carboplatin plus weekly paclitaxel (dose-dense regimen) and carboplatin plus
paclitaxel every 3 weeks were considered. Outcomes included overall survival
(OS), progression free survival (PFS) and severe acute toxicity. RESULTS: Dose
dense regimen was associated with significant improvement of PFS compared with
standard schedule, with HR of 0.73 (95% CI 0.61-0.88, p = 0.001). There was no
difference in OS between treatment regimens (HR 0.95, 95% CI 0.77-1.16, p=0.06),
as well as in term of severe acute toxicity. CONCLUSION: Dose-dense regimen is
superior to standard schedule in terms of PFS. Further studies are necessary to
firmly confirm this evidence in advanced OC treatment.
PMID- 27509062
TI - Interferon gamma peptidomimetic targeted to interstitial myofibroblasts
attenuates renal fibrosis after unilateral ureteral obstruction in mice.
AB - Renal fibrosis cannot be adequately treated since anti-fibrotic treatment is
lacking. Interferon-gamma is a pro-inflammatory cytokine with anti-fibrotic
properties. Clinical use of interferon-gamma is hampered due to inflammation
mediated systemic side effects. We used an interferon-gamma peptidomimetic
(mimgamma) lacking the extracellular IFNgammaReceptor recognition domain, and
coupled it to the PDGFbetaR-recognizing peptide BiPPB. Here we tested the
efficacy of mimgamma-BiPPB (referred to as "Fibroferon") targeted to PDGFbetaR
overexpressing interstitial myofibroblasts to attenuate renal fibrosis without
inducing inflammation-mediated side effects in the mouse unilateral ureter
obstruction model.Unilateral ureter obstruction induced renal fibrosis
characterized by significantly increased alpha-SMA, TGFbeta1, fibronectin, and
collagens I and III protein and/or mRNA expression. Fibroferon treatment
significantly reduced expression of these fibrotic markers. Compared to full
length IFNgamma, anti-fibrotic effects of Fibroferon were more pronounced.
Unilateral ureter obstruction-induced lymphangiogenesis was significantly reduced
by Fibroferon but not full-length IFNgamma. In contrast to full-length IFNgamma,
Fibroferon did not induce IFNgamma-related side-effects as evidenced by preserved
low-level brain MHC II expression (similar to vehicle), lowered plasma
triglyceride levels, and improved weight gain after unilateral ureter
obstruction.In conclusion, compared to full-length IFNgamma, the IFNgamma
peptidomimetic Fibroferon targeted to PDGFbetaR-overexpressing myofibroblasts
attenuates renal fibrosis in the absence of IFNgamma-mediated adverse effects.
PMID- 27509064
TI - Simulation-based Randomized Comparative Assessment of Out-of-Hospital Cardiac
Arrest Resuscitation Bundle Completion by Emergency Medical Service Teams Using
Standard Life Support or an Experimental Automation-assisted Approach.
AB - INTRODUCTION: Effective resuscitation of out-of-hospital cardiac arrest (OHCA)
patients is challenging. Alternative resuscitative approaches using
electromechanical adjuncts may improve provider performance. Investigators
applied simulation to study the effect of an experimental automation-assisted,
goal-directed OHCA management protocol on EMS providers' resuscitation
performance relative to standard protocols and equipment. METHODS: Two-provider
(emergency medical technicians (EMT)-B and EMT-I/C/P) teams were randomized to
control or experimental group. Each team engaged in 3 simulations: baseline
simulation (standard roles); repeat simulation (standard roles); and abbreviated
repeat simulation (reversed roles, i.e., basic life support provider performing
ALS tasks). Control teams used standard OHCA protocols and equipment (with high
performance cardiopulmonary resuscitation training intervention); for second and
third simulations, experimental teams performed chest compression,
defibrillation, airway, pulmonary ventilation, vascular access, medication, and
transport tasks with goal-directed protocol and resuscitation-automating devices.
Videorecorders and simulator logs collected resuscitation data. RESULTS: Ten
control and 10 experimental teams comprised 20 EMT-B's; 1 EMT-I, 8 EMT-C's, and
11 EMT-P's; study groups were not fully matched. Both groups suboptimally
performed chest compressions and ventilations at baseline. For their second
simulations, control teams performed similarly except for reduced on-scene time,
and experimental teams improved their chest compressions (P=0.03), pulmonary
ventilations (P<0.01), and medication administration (P=0.02); changes in their
performance of chest compression, defibrillation, airway, and transport tasks did
not attain significance against control teams' changes. Experimental teams
maintained performance improvements during reversed-role simulations. CONCLUSION:
Simulation-based investigation into OHCA resuscitation revealed considerable
variability and improvable deficiencies in small EMS teams. Goal-directed,
automation-assisted OHCA management augmented select resuscitation bundle element
performance without comprehensive improvement.
PMID- 27509065
TI - Psychosomatic Medicine in Germany: More Timely than Ever.
PMID- 27509066
TI - A validated, sensitive HPLC-MS/MS method for quantification of cis-para-methyl-4
methylaminorex (cis-4,4'-DMAR) in rat and human plasma: application to
pharmacokinetic studies in rats.
AB - 4,4'-DMAR is an analogue of the known psychostimulants 4-methylaminorex and
aminorex. In the light of reports of deaths associated with its abuse, and the
easy access from Internet vendors, the EU Council recently decided on control
measures across member states. Here we describe a validated method for measuring
plasma levels of cis-4,4'-DMAR, crucial for preclinical studies and analysis in
human plasma. Chromatographic separation was done by gradient elution on a
Kinetex C18 column with 0.1% formic acid in water and 0.1% formic acid in
acetonitrile at 0.2 mL/min. Detection was by positive electrospray ionization
(ESI+) in multiple reaction monitoring mode monitoring the quantifier transitions
m/z 191.4 -> m/z 148.3 for cis-4,4'-DMAR and m/z 259.3 -> m/z 194.2 for
carbamazepine (internal standard). Protein precipitation with 1% of formic acid
in acetonitrile was used in cis-4,4'-DMAR extraction from plasma; recovery was
high (>93%) with a negligible matrix effect. This method provides an accurate,
precise, and sensitive method for cis-4,4'-DMAR quantification in human and rat
plasma, following European Medicine Agency guidelines for bioanalytical method
validation. Pharmacokinetic studies were conducted in rats. After an intravenous
dose of 1 mg/kg, plasma levels declined rapidly (>=80% in 4 h), followed by a
slow elimination phase (t1/2 of 5.14 +/- 0.65 h). Absorption was rapid after
intraperitoneal injection (tmax = 15 min) with a rapid decline thereafter; Cmax
and AUC0-240min showed dose-proportionality over the dose range 1-10 mg/kg. This
method was successfully applied to investigate pharmacokinetic properties in rats
and could be used to quantify cis-4,4'-DMAR levels in human plasma. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27509063
TI - TIMP-1 is under regulation of the EGF signaling axis and promotes an aggressive
phenotype in KRAS-mutated colorectal cancer cells: a potential novel approach to
the treatment of metastatic colorectal cancer.
AB - It is now widely accepted that therapeutic antibodies targeting epidermal growth
factor receptor (EGFR) can have efficacy in KRAS wild-type advanced colorectal
cancer (CRC) patients. What remains to be ascertained is whether a subgroup of
KRAS-mutated CRC patients might not also derive benefit from EGFR inhibitors.
Metalloproteinase inhibitor 1 (TIMP-1) is a pleiotropic factor predictive of
survival outcome of CRC patients. Levels of TIMP-1 were measured in pre-treatment
plasma samples (n = 426) of metastatic CRC patients randomized to Nordic FLOX (5
fluorouracil and oxaliplatin) +/- cetuximab (NORDIC VII study). Multivariate
analysis demonstrated a significant interaction between plasma TIMP-1 protein
levels, KRAS status and treatment with patients bearing KRAS mutated tumors and
high TIMP-1 plasma level (> 3rd quartile) showing a significantly longer overall
survival if treated with cetuximab (HR, 0.48; 95% CI, 0.25 to 0.93). To gain
mechanistic insights into this association we analyzed a set of five different
CRC cell lines. We show here that EGFR signaling induces TIMP-1 expression in CRC
cells, and that TIMP-1 promotes a more aggressive behavior, specifically in KRAS
mutated cells. The two sets of data, clinical and in vitro, are complementary and
support each other, lending strength to our contention that TIMP- 1 plasma levels
can identify a subset of patients with KRAS-mutated metastatic CRC that will have
benefit from EGFR-inhibition therapy.
PMID- 27509068
TI - Cellular Delivery of RNA Nanoparticles.
AB - RNA nanostructures can be programmed to exhibit defined sizes, shapes and
stoichiometries from naturally occurring or de novo designed RNA motifs. These
constructs can be used as scaffolds to attach functional moieties, such as ligand
binding motifs or gene expression regulators, for nanobiology applications. This
review is focused on four areas of importance to RNA nanotechnology: the types of
RNAs of particular interest for nanobiology, the assembly of RNA nanoconstructs,
the challenges of cellular delivery of RNAs in vivo, and the delivery carriers
that aid in the matter. The available strategies for the design of nucleic acid
nanostructures, as well as for formulation of their carriers, make RNA
nanotechnology an important tool in both basic research and applied biomedical
science.
PMID- 27509069
TI - Stereotactic Radiosurgery for Cystic Vestibular Schwannomas.
AB - BACKGROUND: The optimum treatment for cystic vestibular schwannoma (VS) remains
controversial. Anecdotally, many treating physicians feel that cystic VSs do not
respond to stereotactic radiosurgery (SRS) as well as noncystic tumors.
OBJECTIVE: To present outcomes after treatment of predominantly cystic VS with
SRS. METHODS: A prospectively maintained clinical database of patients undergoing
Gamma Knife (Elekta Instruments, Stockholm, Sweden) radiosurgery (GKRS) for VS at
a single tertiary academic referral center was retrospectively reviewed. Patients
diagnosed with cystic VS who were treated with GKRS between 1997 and 2014 were
analyzed. Size-matched solid tumors treated with GKRS during this period were
selected as controls. RESULTS: Twenty patients (12 women; median age at
treatment, 56 years; range, 36-85 years) with cystic VS met inclusion criteria.
The median radiologic follow-up within the cystic group was 63 months (range, 17
201 months), and the median change in tumor size was -4.9 mm (range, -10.4 to 9.3
mm). Sixteen tumors (80%) shrank, 2 (10%) remained stable, and 2 (10%) enlarged,
accounting for a tumor control rate of 90%. The median radiologic follow-up in
the noncystic control group was 67 months (range, 6-141 months), and the median
change in size was -2.0 mm (range, -10.4 to 2.5 mm). Tumor control in the solid
group was 90%. Comparing only those tumors that decreased in size showed that
there was a trend toward a greater reduction within the cystic group ( P = .05).
CONCLUSION: The present study demonstrates that tumor control after SRS for
cystic VS may not differ from that of noncystic VS in selected cases.
PMID- 27509067
TI - Mannose 6-Phosphate Receptor Is Reduced in -Synuclein Overexpressing Models of
Parkinsons Disease.
AB - Increasing evidence points to defects in autophagy as a common denominator in
most neurodegenerative conditions. Progressive functional decline in the
autophagy-lysosomal pathway (ALP) occurs with age, and the consequent impairment
in protein processing capacity has been associated with a higher risk of
neurodegeneration. Defects in cathepsin D (CD) processing and alpha-synuclein
degradation causing its accumulation in lysosomes are particularly relevant for
the development of Parkinson's disease (PD). However, the mechanism by which
alterations in CD maturation and alpha-synuclein degradation leads to autophagy
defects in PD neurons is still uncertain. Here we demonstrate that MPR300
shuttling between endosomes and the trans Golgi network is altered in alpha
synuclein overexpressing neurons. Consequently, CD is not correctly trafficked to
lysosomes and cannot be processed to generate its mature active form, leading to
a reduced CD-mediated alpha-synuclein degradation and alpha-synuclein
accumulation in neurons. MPR300 is downregulated in brain from alpha-synuclein
overexpressing animal models and in PD patients with early diagnosis. These data
indicate MPR300 as crucial player in the autophagy-lysosomal dysfunctions
reported in PD and pinpoint MRP300 as a potential biomarker for PD.
PMID- 27509070
TI - Defining Glioblastoma Resectability Through the Wisdom of the Crowd: A Proof-of
Principle Study.
AB - BACKGROUND: Extent of resection (EOR) correlates with glioblastoma outcomes.
Resectability and EOR depend on anatomical, clinical, and surgeon factors.
Resectability likely influences outcome in and of itself, but an accurate
measurement of resectability remains elusive. An understanding of resectability
and the factors that influence it may provide a means to control a confounder in
clinical trials and provide reference for decision making. OBJECTIVE: To provide
proof of concept of the use of the collective wisdom of experienced brain tumor
surgeons in assessing glioblastoma resectability. METHODS: We surveyed 13
academic tumor neurosurgeons nationwide to assess the resectability of newly
diagnosed glioblastoma. Participants reviewed 20 cases, including digital imaging
and communications in medicine-formatted pre- and postoperative magnetic
resonance images and clinical vignettes. The selected cases involved a variety of
anatomical locations and a range of EOR. Participants were asked about surgical
goal, eg, gross total resection, subtotal resection (STR), or biopsy, and
rationale for their decision. We calculated a "resectability index" for each
lesion by pooling responses from all 13 surgeons. RESULTS: Neurosurgeons'
individual surgical goals varied significantly ( P = .015), but the resectability
index calculated from the surgeons' pooled responses was strongly correlated with
the percentage of contrast-enhancing residual tumor ( R = 0.817, P < .001). The
collective STR goal predicted intraoperative decision of intentional STR
documented on operative notes ( P < .01) and nonresectable residual ( P < .01),
but not resectable residual. CONCLUSION: In this pilot study, we demonstrate the
feasibility of measuring the resectability of glioblastoma through crowdsourcing.
This tool could be used to quantify resectability, a potential confounder in
neuro-oncology clinical trials.
PMID- 27509071
TI - Surgical Management of Carney Complex-Associated Pituitary Pathology.
AB - BACKGROUND: Carney complex (CNC) is a familial neoplasia syndrome that is
associated with pituitary-associated hypersecretion of growth hormone (GH)
(acromegaly). The underlying cause of pituitary GH hypersecretion and its
management have been incompletely defined. OBJECTIVE: To provide biological
insight into CNC-associated pituitary pathology and improve management, we
analyzed findings in CNC patients who underwent transsphenoidal surgery. METHODS:
Consecutive CNC patients at the National Institutes of Health with acromegaly and
imaging evidence of a pituitary adenoma(s) who underwent transsphenoidal
resection of tumor(s) were included. Prospectively acquired magnetic resonance
imaging and biochemical, surgical, and histological data were analyzed. RESULTS:
Seven acromegalic CNC patients (2 male, 5 female) were included. The mean age at
surgery was 29.7 years (range, 18-44 years). The mean follow-up was 4.7 years
(range, 0.2-129 months). Magnetic resonance imaging revealed a single pituitary
adenoma in 4 patients and multiple pituitary adenomas in 3 patients. Whereas
patients with single discrete pituitary adenomas underwent selective
adenomectomy, patients with multiple adenomas underwent selective adenomectomy of
multiple tumors, as well as partial or total hypophysectomy. All adenomas were
either GH and prolactin positive or exclusively prolactin positive. Pituitary
tissue surrounding the adenomas in patients with multiple adenomas revealed
hyperplastic GH- and prolactin-positive tissue. CONCLUSION: CNC-associated
acromegaly results from variable pituitary pathology, including a single GH
secreting adenoma or multiple GH-secreting adenomas and/or GH hypersecretion of
the pituitary gland surrounding multiple adenomas. Although selective
adenomectomy is the preferred treatment for cases of GH-secreting adenomas,
multiple adenomas with associated pituitary gland GH hypersecretion may require
partial or complete hypophysectomy to achieve biochemical remission.
PMID- 27509072
TI - Iodinated X-ray contrast agents: Photoinduced transformation and monitoring in
surface water.
AB - Conventional wastewater treatment methods have shown to be unsuitable for a
complete elimination of iodinated X-ray contrast agents (ICMs), which have thus
been found in wastewater treatment plant (WWTP) effluent and in surface water.
Once in the surface water, they could be transformed through different processes
and form several transformation products that may need to be monitored as well.
To this end, we studied the abatement and transformation of ICMs by combining
laboratory experiments with in field analyses. We irradiated different aqueous
solutions of the selected pollutants in the presence of TiO2 as photocatalyst,
aimed to promote ICMs degradation and to generate photoinduced transformation
products (TPs) similar to those occurring in the environment and effluent
wastewater. This experimental strategy has been applied to the study of three
ICMs, namely iopromide, iopamidol and diatrizoate. A total of twenty-four, ten,
and ten TPs were detected from iopamidol, diatrizoate and iopromide,
respectively. The analyses were performed using a liquid chromatography-LTQ-FT
Orbitrap mass spectrometer. The mineralization process and acute toxicity
evolution were assessed as well over time and revealed a lack of mineralization
for all ICMs and the formation of harmful byproducts. After characterizing these
transformation products, WWTP effluent and surface water taken from several
branches of the Chicago River were analyzed for ICMs and their TPs. HRMS with
MS/MS fragmentation was used as a confirmatory step for proper identification of
compounds in water and wastewater samples. All three of ICM were detected in the
effluent and surface water samples, while no significant amount of TPs were
detected.
PMID- 27509073
TI - POPs in the South Latin America: Bioaccumulation of DDT, PCB, HCB, HCH and Mirex
in blubber of common dolphin (Delphinus delphis) and Fraser's dolphin
(Lagenodelphis hosei) from Argentina.
AB - Organic compounds, in particular organochlorines, are highly persistent compounds
which accumulate in biotic and abiotic substrates. Marine mammals bioaccumulate
and biomagnify persistent organic pollutants (POPs) through diet. ?PCB (26 PCB
congeners), ?DDT (pp-DDT, pp-DDD, pp-DDE), ?HCH (alpha-HCH, beta-HCH, gamma-HCH,
delta-HCH), HCB and mirex were analyzed from samples of subcutaneous adipose
tissue of common dolphins, Delphinus delphis, and Fraser's dolphins,
Lagenodelphis hosei, obtained in 1999 and 2012. The aim of this study was to
determine the concentrations of POPs to get baseline information on the current
state of pollution by these compounds in these two species in South Atlantic. At
the same time, to assess concentrations of POPs in relation to age, the total
length and sexual maturity in common dolphins. Organochlorine pesticides
dominated Fraser's dolphins, DDT being the most abundant, while PCBs were mostly
present in common dolphins. In both species, the distributions of isomers or
metabolites followed the order: beta-HCH>delta-HCH>gamma-HCH>alpha-HCH and pp
DDE>pp-DDD>pp-DDT. As for ?PCB, the largest contribution was given by congeners
of high molecular weight, particularly by hexa and hepta - CBs. Common dolphins
did not show effects on sexual maturity, age and standard length in the
concentration of organochlorines. The mean concentrations found in this study are
lower compared to those reported in other studies performed in dolphins
elsewhere. This study provides new information regarding levels of
organochlorines in common dolphins for the Southwestern Atlantic.
PMID- 27509074
TI - Reduction of Cr (VI) into Cr (III) by organelles of Chlorella vulgaris in aqueous
solution: An organelle-level attempt.
AB - The priority pollutant chromium (Cr) was ubiquitous and great efforts have been
made to reduce Cr (VI) into less-toxic Cr (III) by alga for the convenient
availability and low expense. However, the functional role of organelle inside
the algal cell in Cr (VI) reduction was poorly understood. In this study,
organelles in green algae Chlorella vulgaris were extracted and further decorated
for Cr (VI) reduction tests. Results showed that the chloroplast exhibited not
only adsorption ability of total Cr (21.18% comparing to control) but also
reduction potential of Cr (VI) (almost 70% comparing to control), whose most
suitable working concentration was at 17MUg/mL. Furtherly, the isolated thylakoid
membrane (ITM) showed better Cr (VI) reduction potential with the presence of
sodium alginate (SA), even though the Hill reaction activity (HRA) was inhibited.
As for photosystem II (PSII), the addition of mesoporous silica SBA-15 enhanced
the reduction ability through improving the light-harvesting complex (LHC) II
efficiency and electron transport rate. On the whole, the reduction ability order
of the three kinds of materials based on chloroplast in C. vulgaris was PSII@SBA
15>Chloroplast>ITM@SA. The attempt made in this study to reduce the Cr (VI) with
C. vulgaris organelles might not only offer basement to detect the potential
action mechanism of Cr (VI) reduction by C. vulgaris but also provide a new sight
for the scavenge of heavy metal with biological materials.
PMID- 27509075
TI - Quantitative relationships between the adsorptivity of carbonaceous materials in
soil for Pb(II) and soil organic matter content.
AB - Strong adsorptivity of manufactured carbonaceous materials (MCMs) mediates the
behavior of heavy metals in soil. Laboratory-reported adsorptivity of MCMs often
deviates from their actual abilities in soil, because soil organic matter (SOM)
can change the adsorptive abilities of MCMs by coating dissolved organic matter
(DOM) on the surface of the MCMs. It was considered that the influence of SOM on
the adsorptivity of MCMs in soil follows a sequential pathway of SOM releasing
DOM in soil solution and subsequent DOM binding onto MCMs, thereby altering MCM
surface acidity and hence changing MCM adsorptivity for heavy metals. In this
study, we first extracted DOM from ten topsoils collected over a broad region of
China with a wide range of SOM. The DOM solutions were then used to load DOM onto
four MCMs including activated carbon (AC), multiwalled carbon nanotube (MWCNT),
and two biochars (BC400 and BC700), respectively, obtaining a total of 44 MCM-DOM
complex samples with known amounts of bound DOM. These MCM-DOM complex samples
were then determined for their surface acidities and adsorptive abilities for
Pb(II). We found that there were significant correlations between DOM
concentration and SOM content, between DOM binding onto MCMs and DOM
concentration, between surface acidity of MCM-DOM complexes and DOM binding onto
MCMs, as well as between Pb(II) adsorption on MCM-DOM complexes and surface
acidity of MCM-DOM complexes. With understanding of these individual linear
correlations, linear relationships between the Pb(II) adsorption and SOM content
were established by combining individual correlations and by directly plotting
the former against the latter. These relationships may be used to accurately
predict the adsorptive abilities of MCMs for heavy metals in soils via simply
determining SOM.
PMID- 27509076
TI - On the origin of the highest ozone episodes in Spain.
AB - The 2000-2015 occurrences of the highest ozone (O3) pollution episodes in Spain
were evaluated to investigate their origin. To this end, data series available
for urban and regional background (UB and RB), traffic (TR) and industrial (IN)
sites were analysed separately and intercompared. Results evidenced that during
these 16years mean O3 levels in the RB sites did not change significantly, and
remained constantly high. However, there is a clear increase at the TR and UB
sites. Although sensitivity analysis is needed to interpret the cause of this
increasing trend, this might be caused probably by the lower O3 titration
intensity due to the preferential abatement of NO vs NO2, as supported from the
neutral trend of OX (NO2+O3) at these sites. We found that the exceedances of the
hourly information threshold for O3 (>180MUg/m3) are recorded mostly at UB and IN
sites located in seven areas of Spain (specific hotspots or at the tail end of
large urban plumes), and that these increased during summer heatwaves (i.e. 2003
and 2015). Although the external contribution of regional-to-subcontinental
transported O3 might be relevant during the highest O3 episodes in the Western
Mediterranean, our results evidenced that in the above specific areas, regional
local O3 production decisively contributes to the exceedances of the information
threshold. Also that the human protection threshold and the AOT40 are more
frequently exceeded in the Central, Southern and Mediterranean sides of the
Iberian Peninsula. The design of effective episode abatement measures is quite
complex in those conditions, due to both the nonlinearity of the chemical
processes of O3 formation and destruction, and to the interplay with the complex
meteorological setting, causing frequent recirculation and in situ aging of air
masses. However, the combination of meteorological forecasting of the main
recirculation processes and sensitivity analysis of NOX/VOC emission abatement
measures might be powerful tools to evaluate the effectiveness of potential O3
mitigation strategies. Finally we would like to highlight that the current UB,
RB, IN and TR classification (somewhat subjective) is not adequate to interpret
the origin of O3 exceedances in complex areas of Southern Europe. Thus, a UB
station recording exceedances, and located in a small city in the tail end of an
urban plume of a large city, receives not only the contribution from its own UB,
but mainly from the specific high O3 RB caused by the urban plume transport.
PMID- 27509079
TI - Acne during adolescence did not predict skin rash reaction to cetuximab.
AB - Cetuximab, a monoclonal antibody, is a part of the treatment for metastatic
colorectal cancer. The most common side effect of cetuximab is skin rash, which
has a similar distribution to acne vulgaris and some overlapping
pathophysiological mechanisms. The aim of the current study was to determine
whether acne vulgaris in adolescence (AinA) is predictive of a cetuximab-related
rash to better understand the pathogenesis of this side effect and explore
potential preventive actions. From July 2013 to June 2015, patients with
metastatic colorectal cancer planned for treatment with cetuximab were enrolled
in the study. Before initiating treatment, patients completed a questionnaire
evaluating endocrine disorders, other chronic diseases, smoking, chronic
medications, allergies, and dermatologic history of AinA and its severity.
Patients were followed for 6 months. Data were collected from 32 participants (16
women, 16 men). Twenty-three (69%) patients experienced a cetuximab-associated
skin reaction. Nine (28%) patients had a history of AinA. Of these, seven
developed a cetuximab-associated skin reaction. Three of the five (60%) patients
who used proton pump inhibitors (PPIs) developed severe (grades 3-4) skin
toxicity versus 4/27 (15%) patients who were not on PPIs (P=0.057). The degree of
skin toxicity correlated to the median time-to-tumor-progression: 2 months for
patients with grades 0-1 compared with 5.5 months for grades 2-4 skin toxicity
(P=0.047, 95% confidence interval 1.06-4.95). No significant correlation was
found between AinA and cetuximab-associated skin reactions. The correlation
between PPI treatment and severe skin toxicity related to cetuximab should be
examined further.
PMID- 27509077
TI - Economic Analysis of the Impact of Overseas and Domestic Treatment and Screening
Options for Intestinal Helminth Infection among US-Bound Refugees from Asia.
AB - BACKGROUND: Many U.S.-bound refugees travel from countries where intestinal
parasites (hookworm, Trichuris trichuria, Ascaris lumbricoides, and Strongyloides
stercoralis) are endemic. These infections are rare in the United States and may
be underdiagnosed or misdiagnosed, leading to potentially serious consequences.
This evaluation examined the costs and benefits of combinations of overseas
presumptive treatment of parasitic diseases vs. domestic screening/treating vs.
no program. METHODS: An economic decision tree model terminating in Markov
processes was developed to estimate the cost and health impacts of four
interventions on an annual cohort of 27,700 U.S.-bound Asian refugees: 1) "No
Program," 2) U.S. "Domestic Screening and Treatment," 3) "Overseas Albendazole
and Ivermectin" presumptive treatment, and 4) "Overseas Albendazole and Domestic
Screening for Strongyloides". Markov transition state models were used to
estimate long-term effects of parasitic infections. Health outcome measures (four
parasites) included outpatient cases, hospitalizations, deaths, life years, and
quality-adjusted life years (QALYs). RESULTS: The "No Program" option is the
least expensive ($165,923 per cohort) and least effective option (145 outpatient
cases, 4.0 hospitalizations, and 0.67 deaths discounted over a 60-year period for
a one-year cohort). The "Overseas Albendazole and Ivermectin" option ($418,824)
is less expensive than "Domestic Screening and Treatment" ($3,832,572) or
"Overseas Albendazole and Domestic Screening for Strongyloides" ($2,182,483).
According to the model outcomes, the most effective treatment option is "Overseas
Albendazole and Ivermectin," which reduces outpatient cases, deaths and
hospitalization by around 80% at an estimated net cost of $458,718 per death
averted, or $2,219/$24,036 per QALY/life year gained relative to "No Program".
DISCUSSION: Overseas presumptive treatment for U.S.-bound refugees is a cost
effective intervention that is less expensive and at least as effective as
domestic screening and treatment programs. The addition of ivermectin to
albendazole reduces the prevalence of chronic strongyloidiasis and the
probability of rare, but potentially fatal, disseminated strongyloidiasis.
PMID- 27509078
TI - Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin
1beta Production during Infection.
AB - Previous studies have shown that the pro-inflammatory cytokine IL-1beta has a
crucial role in host defenses against group B streptococcus (GBS), a frequent
human pathogen, by recruiting neutrophils to infection sites. We examined here
the cell types and mechanisms involved in IL-1beta production during infection.
Using a GBS-induced peritonitis model in mice, we first found that a large
proportion of exudate cells contain intracellular IL-1beta by immunofluorescence.
Of the IL-1beta positive cells, 82 and 7% were neutrophils and macrophages,
respectively, suggesting that the former cell type might significantly contribute
to IL-1beta production. Accordingly, depletion of neutrophils with anti-Ly6G
antibodies resulted in a significant reduction in the levels of IL-1beta, but not
of TNF-alpha or IL-6. We next found that neutrophils are capable of releasing
mature IL-1beta and TNF-alpha directly in response to in vitro stimulation with
GBS. The production of pro-IL-1beta and TNF-alpha in these cells required the
Toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1, which
is involved in mobilization of a subfamily of TLRs to the endosomes. Moreover,
pro-IL-1beta processing and IL-1beta release was triggered by GBS hemolysin and
required components of the canonical inflammasome, including caspase-1, ASC and
NLRP3. Collectively our findings indicate that neutrophils make a significant
contribution to IL-1beta production during GBS infection, thereby amplifying
their own recruitment. These cells directly recognize GBS by means of endosomal
TLRs and cytosolic sensors, leading to activation of the caspase-1 inflammasome.
PMID- 27509080
TI - Incorporating peer-to-peer facilitation with a mid-level fidelity student led
simulation experience for undergraduate nurses.
AB - BACKGROUND: The aim of this study was to evaluate peer-to-peer facilitated
student led mid-level fidelity simulation experiences. METHODS: Second and third
year nursing students (N = 637) were invited to complete a 16-item 6-point Likert
scale questionnaire after the simulation experience. RESULTS: Students reported
high self-confidence in their nursing skills (M = 4.14, SD = 0.92) and a high
level of satisfaction in the learning they received during the peer-to-peer
facilitated student led simulation experience (M = 4.42, SD = 0.93). CONCLUSION:
Using peer-to-peer teaching strategies during student led simulation experience
is an effective approach for ensuring active engagement of all learners during
midlevel fidelity group-based simulations and has the potential for broad
applicability.
PMID- 27509082
TI - Receipt of vaginal brachytherapy is associated with improved survival in women
with stage I endometrioid adenocarcinoma of the uterus: A National Cancer Data
Base study.
AB - BACKGROUND: Randomized controlled trials have consistently shown that the use of
postoperative radiotherapy (RT) for stage I endometrial cancer leads to a
reduction in the incidence of pelvic recurrences without a corresponding
reduction in overall mortality. It was hypothesized that a reduction in mortality
associated with the receipt of RT could be identified in a large data set with
greater statistical power. METHODS: Women with surgically staged IA or IB
endometrial adenocarcinoma who were treated with total hysterectomy between 2003
and 2011 were identified in the National Cancer Data Base. Chi-square tests and
multivariate logistic regression were performed to analyze factors associated
with the treatment type. A survival analysis was performed with log-rank testing,
Cox proportional hazards regression, and Kaplan-Meier estimates. RESULTS: A total
of 44,309 eligible women were identified (33,380 at stage IA and 10,929 at stage
IB): 88.4% of the women with stage IA tumors and 51.6% of the women with stage IB
tumors received no RT. Older age, comorbid disease, a higher histologic grade,
and a larger tumor size were independently associated with an increase in
mortality. The receipt of vaginal brachytherapy (VB) was independently associated
with a reduction in mortality for both stage IA disease (hazard ratio [HR], 0.81;
95% confidence interval [CI], 0.67-0.97) and stage IB disease (HR, 0.62; 95% CI,
0.51-0.74). CONCLUSIONS: Analyses of this large database support the utility of
postoperative VB for many women with stage I endometrial cancer. Unfortunately,
RT appears to be underused in this population. Greater adherence to consensus
guidelines may lead to improved outcomes. Cancer 2016;122:3724-31. (c) 2016
American Cancer Society.
PMID- 27509083
TI - Influenza Vaccination Coverage Rates, Knowledge, Attitudes, and Beliefs in
Jordan: A Comprehensive Study.
AB - Influenza vaccination is the most effective method in preventing influenza and
its complications. This study's objectives were to investigate the vaccination
coverage and frequency and to assess knowledge, attitudes, and practices toward
influenza vaccination in Jordan during the year 2012 and the 5 years preceding
it. Additionally, it aimed at identifying the barriers and motivations to receive
the vaccine and the factors contributing to its uptake. In May 2012, a self
administered cross-sectional survey was distributed to 3,200 adults conveniently
selected across Jordan to explore influenza vaccination status, knowledge,
attitudes, and practices toward the influenza vaccine. The survey response rate
was 98.3%. The overall coverage rate of seasonal influenza vaccination ranged
from 9.9% to 27.5%. Results of the univariate analysis revealed that males,
participants older than 45 years, business owners, and university students or
graduates were more likely to take the vaccine. Healthcare workers (HCW) showed
higher rates than non-HCW and those with concomitant chronic diseases were more
committed to receive the vaccine. Knowledge about the influenza vaccine is
considered high in the Jordanian population. Fear from side effects was the major
barrier, while the fear of the virus spread and outbreak was the major reason to
receive the vaccine. The coverage rates were low in Jordan compared to other
countries. The need for influenza vaccine campaigns and on-going education in
Jordan health schools is crucial to increase the rate and remove misconceptions
and negative attitudes toward vaccination.
PMID- 27509084
TI - A Two-Dimensional Inorganic-Organic Hybrid Solid of Manganese(II)
Hydrogenophosphate Showing High Proton Conductivity at Room Temperature.
AB - The inorganic-organic hybrid metal hydrogenophosphate with a formula of
(C2H10N2)[Mn2(HPO4)3](H2O) (1) shows layered crystal structure. The inorganic
anion layer is built from Mn3O13 cluster units, and the interlayer spaces are
filled by the charge-compensated ethylenediammonium dications together with the
lattice water molecules. The thermogravimetry, variable-temperature powder X-ray
diffraction, and the proton conductance under anhydrous and moisture environments
were investigated for 1, disclosing that 1 shows high thermal stability and high
proton transport nature, and the proton conductivity reaches to 1.64 * 10(-3)
S.cm(-1) under 99%RH even at 293 K. The high proton conductivity is related to
the formation of denser H-bond networks in the lattice.
PMID- 27509085
TI - Changing the chemical and physical properties of high valent heterobimetallic bis
(MU-oxido) Cu-Ni complexes by ligand effects.
AB - Two new heterobimetallic [LNiO2Cu(RPY2)]+ (RPY2 = N-substituted bis 2
pyridyl(ethylamine) ligands with R = indane, 3a or R = Me, 3b) complexes have
been spectroscopically trapped at low temperatures. They were prepared by
reacting the mononuclear side-on LNiII superoxo precursor bearing a beta
diketiminate ligand (L = [HC-(CMeNC6H3(iPr)2)2]) with the Cu(i) complexes. In
contrast to the oxo groups in known high-valent [M2(MU-O)2]n+ (M = Fe, Co, Ni,
Cu) cores that display electrophilic reactivities, 3a and 3b display rather
nucleophilic oxo cores active in aldehyde deformylation reactions. However, the
spectroscopic and reactivity properties of 3a/3b are found to be distinct
relative to that of the previously reported [LNiO2Cu(MeAN)]+ complex containing a
more basic (nucleophilic) N,N,N',N',N'-pentamethyl-dipropylenetriamine (MeAN)
ligand at the copper centre. The geometry and electronic properties of the copper
ligands affect the electron density of the oxygen atoms of the heterodinuclear
{Ni(MU-O)2} core and 3a/3b undergo slower nucleophilic and faster electrophilic
reactions than the previously reported [LNiO2Cu(MeAN)]+ intermediate. The present
study therefore demonstrates the tuning of the electrophilicity/nucleophilicity
of the oxygen atoms of the heterobimetallic [Ni(MU-O)2Cu]2+ cores by controlling
the electron donation from the ancillary ligands, and underlines the significance
of subtle electronic changes in the physical and chemical properties of the
biologically relevant heterobimetallic metal-dioxygen intermediates.
PMID- 27509086
TI - Paired-Pulse TMS and Fine-Wire Recordings Reveal Short-Interval Intracortical
Inhibition and Facilitation of Deep Multifidus Muscle Fascicles.
AB - OBJECTIVE: Paired-pulse transcranial magnetic stimulation (ppTMS) is used to
probe inhibitory and excitatory networks within the primary motor cortex (M1).
These mechanisms are identified for limb muscles but it is unclear whether they
share properties with trunk muscles. The aim was to determine whether it was
possible to test the intracortical inhibition and facilitation of the deep
multifidus muscle fascicles (DM) and at which inter-stimulus intervals (ISI).
METHODS: In ten pain-free individuals, TMS was applied over M1 and motor evoked
potentials (MEP) were recorded using fine-wire electrodes in DM. MEPs were
conditioned with subthreshold stimuli at ISIs of 1 to 12 ms to test short
interval intracortical inhibition (SICI) and at 15 ms for long-interval
intracortical facilitation. Short-interval facilitation (SICF) was tested using 1
ms ISI. RESULTS: SICI of DM was consistently obtained with ISI of 1-, 3-, 4- and
12-ms. Facilitation of DM MEP was only identified using SICF paradigm.
CONCLUSIONS: A similar pattern of MEP modulation with ISI changes for deep trunk
and limb muscles implies that M1 networks share some functional properties.
SIGNIFICANCE: The ppTMS paradigm presents a potential to determine how M1
inhibitory and excitatory mechanisms participate in brain re-organization in back
pain that affects control of trunk muscles.
PMID- 27509087
TI - Quality of the Exotic Parasitoid Cotesia flavipes (Hymenoptera: Braconidae) Does
Not Show Deleterious Effects after Inbreeding for 10 Generations.
AB - Although the parasitoid Cotesia flavipes (Cameron) has proven effective in
controlling sugarcane borer Diatraea saccharalis (Fabricius) for many years,
concern has arisen over the quality of individuals produced at large scales. The
parasitoid has been reared in laboratories in Brazil for more than 40 years, with
no new introductions of new populations during that period. Since the quality of
the parasitoids was not verified at the time of the species' introduction in
Brazil, we do not know if there has been any reduction in quality so far.
However, it is possible to determine whether the parasitoid could reduce in
quality in future generations. Thus, the objective of this research was to assess
the quality of these insects over 10 generations and look for evidence of any
loss in quality. We used two populations: one from a biofactory that has been
maintained in the laboratory for over 40 years, and an inbred laboratory
population. Both were bred, and compared for 10 generations. We wanted to
determine what happened to the quality of the parasitoid after 10 generations in
an extreme inbreeding situation. To assure inbreeding, newly emerged females were
forced to mate with a sibling. Individual females were then allowed to parasitize
larvae of D. saccharalis. We performed evaluations for each generation until the
tenth generation, and recorded the sex ratio, percentage emergence, number of
offspring/females, and longevity of both males and females. Results of the
measurements of biological characteristics demonstrated random significant
differences between populations; best results were obtained intermittently for
both the biofactory population and the inbred population. No significant
differences across generations for the same population were observed. Thus,
rearing of a C. flavipes population subjected to inbreeding for 10 generations
was not sufficient to reveal any deleterious effects of inbreeding.
PMID- 27509089
TI - Asymmetric Hydrogenation of Unprotected Indoles Catalyzed by eta(6)-Arene/N-Me
sulfonyldiamine-Ru(II) Complexes.
AB - Protecting-group-free transformation is a challenging and important issue in atom
economical organic synthesis. The eta(6)-arene/N-Me-sulfonyldiamine-Ru(II)-BF4
complex-catalyzed asymmetric hydrogenation of 2-substituted unprotected indoles
in weakly acidic hexafluoroisopropanol gives optically active indoline compounds
with up to >99% ee. Under mild reaction media, halogen atoms and synthetically
important protecting groups (e.g., silyl ether, acetal, benzyl ether, and ester)
on indoles are maintained, which is advantageous for the synthesis of further
complex indoline molecules.
PMID- 27509088
TI - Managing Climate Change Refugia for Climate Adaptation.
AB - Refugia have long been studied from paleontological and biogeographical
perspectives to understand how populations persisted during past periods of
unfavorable climate. Recently, researchers have applied the idea to contemporary
landscapes to identify climate change refugia, here defined as areas relatively
buffered from contemporary climate change over time that enable persistence of
valued physical, ecological, and socio-cultural resources. We differentiate
historical and contemporary views, and characterize physical and ecological
processes that create and maintain climate change refugia. We then delineate how
refugia can fit into existing decision support frameworks for climate adaptation
and describe seven steps for managing them. Finally, we identify challenges and
opportunities for operationalizing the concept of climate change refugia.
Managing climate change refugia can be an important option for conservation in
the face of ongoing climate change.
PMID- 27509091
TI - Rigorous 3-dimensional spectral data activity relationship approach modeling
strategy for ToxCast estrogen receptor data classification, validation, and
feature extraction.
AB - The estrogenic potential (expressed as a score composite of 18 high throughput
screening bioassays) of 1528 compounds from the ToxCast database was modeled by a
3-dimensional spectral data activity relationship approach (3D-SDAR). Due to a
lack of 17 O nuclear magnetic resonance (NMR) simulation software, the most
informative carbon-carbon 3D-SDAR fingerprints were augmented with indicator
variables representing oxygen atoms from carbonyl and carboxamide, ester,
sulfonyl, nitro, aliphatic hydroxyl, and phenolic hydroxyl groups. To evaluate
the true predictive performance of the authors' model the United States
Environmental Protection Agency provided them with a blind test set consisting of
2008 compounds. Of these, 543 had available literature data-their binding
affinity served to estimate the external classification accuracy of the developed
model: predictive accuracy of 0.62, sensitivity of 0.71, and specificity of 0.53
were obtained. Compared with alternative modeling techniques, the authors' model
displayed very little reduction in performance between the modeling and the
prediction set. A 3D-SDAR mapping technique allowed identification of structural
features essential for estrogenicity: 1) the presence of a phenolic OH group or
cyclohexenone, 2) a second aromatic or phenolic ring at a distance of 6 A to 8 A
from the oxygen of the first phenol ring, 3) the presence of a methyl group
approximately 6 A away from the centroid of a phenol ring, and 4) a carbonyl
group in close proximity (~4 A measured to the centroid) to 1 of the phenol
rings. Environ Toxicol Chem 2017;36:823-830. Published 2016 Wiley Periodicals
Inc. on behalf of SETAC. This article is a US government work and, as such, is in
the public domain in the United States of America.
PMID- 27509090
TI - Dipeptidyl peptidase- IV inhibitor alogliptin improves stress-induced insulin
resistance and prothrombotic state in a murine model.
AB - BACKGROUND: Stress evokes lipolytic release of free fatty acid (FFA) and low
grade inflammation in visceral adipose tissue, mediated by increased adipokine
secretion, and contributes to glucose metabolism disorder and prothrombotic
state. We tested the hypothesis that alogliptin, a dipeptidyl peptidase-4
inhibitor, can ameliorate the biological effects of chronic stress in mice.
METHOD AND RESULTS: C57BL/6J mice were subjected to 2-week intermittent restraint
stress and orally treated with vehicle or alogliptin (dose: 15 or 45mg/kg/day).
Plasma levels of lipids, proinflammatory cytokines (monocyte chemoattractant
protein-1, tumor necrosis factor-alpha, and interleukin-6), and 8
hydroxydeoxyguanosine were measured with enzyme-linked immunosorbent assay.
Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT) was
examined by CD11b-positive cell count and mRNA expression of CD68 and F4/80 was
examined by immunohistochemistry and RT-PCR, respectively. The mRNA levels of the
above-mentioned proinflammatory cytokines, NADPH oxidase 4, adiponectin, and
coagulation factors (plasminogen activation inhibitor-1 and tissue factor) in WAT
were also assessed with RT-PCR. Glucose metabolism was assessed by glucose and
insulin tolerance tests, plasma levels of DPP-4 activity, glucagon-like peptide
1, expression of DPP-4, insulin receptor substrate-1 and glucose transporter 4 in
WAT and skeletal muscle. Alogliptin administration suppressed stress-induced FFA
release, oxidative stress, adipose tissue inflammation, DPP-4 activation, and
prothrombotic state in a dose-dependent manner, and improved insulin sensitivity
in stressed mice. CONCLUSIONS: The results indicate that alogliptin improves
stress-induced prothrombotic state and insulin resistance; suggesting that
alogliptin could have beneficial therapeutic effects against cardiovascular
complications in diabetic patients under stress.
PMID- 27509092
TI - Syntax Score and Major Adverse Cardiac Events in Patients with Suspected Coronary
Artery Disease: Results from a Cohort Study in a University-Affiliated Hospital
in Southern Brazil.
AB - Background:: The importance of coronary anatomy in predicting cardiovascular
events is well known. The use of traditional anatomical scores in routine
angiography, however, has not been incorporated to clinical practice. SYNTAX
score (SXscore) is a scoring system that estimates the anatomical extent of
coronary artery disease (CAD). Its ability to predict outcomes based on a
baseline diagnostic angiography has not been tested to date. Objective:: To
evaluate the performance of the SXscore in predicting major adverse cardiac
events (MACE) in patients referred for diagnostic angiography. Methods::
Prospective cohort of 895 patients with suspected CAD referred for elective
diagnostic coronary angiography from 2008 to 2011, at a university-affiliated
hospital in Brazil. They had their SXscores calculated and were stratified in
three categories: no significant CAD (n = 495), SXscoreLOW-INTERMEDIATE: < 23 (n
= 346), and SXscoreHIGH: >= 23 (n = 54). Primary outcome was a composite of
cardiac death, myocardial infarction, and late revascularization. Secondary
endpoints were the components of MACE and death from any cause. Results:: On
average, patients were followed up for 1.8 +/- 1.4 years. The primary outcome
occurred in 2.2%, 15.3%, and 20.4% in groups with no significant CAD, SXscoreLOW
INTERMEDIATE, and SXscoreHIGH, respectively (p < 0.001). All-cause death was
significantly higher in the SXscoreHIGH compared with the 'no significant CAD'
group, 16.7% and 3.8% (p < 0.001), respectively. After adjustment for confounding
factors, all outcomes remained associated with the SXscore. Conclusions:: SXscore
independently predicts MACE in patients submitted to diagnostic coronary
angiography. Its routine use in this setting could identify patients with worse
prognosis. Fundamento:: A importancia da anatomia coronariana na predicao de
eventos cardiovasculares e bem conhecida. O uso de escores anatomicos
tradicionais na cineangiocoronariografia de rotina, entretanto, nao foi
incorporado a pratica clinica. O SYNTAX escore (SXescore) e um sistema de escore
que estima a extensao anatomica da doenca arterial coronariana (DAC). Sua
capacidade para predizer desfechos com base na cineangiocoronariografia
diagnostica de base ainda nao foi testada. Objetivo:: Avaliar o desempenho do
SXescore para predizer eventos cardiacos adversos maiores (MACE) em pacientes
encaminhados para cineangiocoronariografia diagnostica. Metodos:: Coorte
prospectiva de 895 pacientes com suspeita de DAC encaminhados para
cineangiocoronariografia diagnostica eletiva de 2008 a 2011, em hospital
universitario no Brasil. Os pacientes tiveram seus SXescores calculados e foram
estratificados em tres categorias: 'sem DAC significativa' (n = 495);
SXescoreBAIXO-INTERMEDIARIO: < 23 (n = 346); e SXescoreALTO: >= 23 (n = 54). O
desfecho primario foi composto de morte cardiaca, infarto do miocardio e
revascularizacao tardia. Os desfechos secundarios foram MACE e morte por todas as
causas. Resultados:: Em media, os pacientes foram acompanhados por 1,8 +/- 1,4
anos. Desfecho primario ocorreu em 2,2%, 15,3% e 20,4% nos grupos 'sem DAC
significativa', SXescoreBAIXO-INTERMEDIARIO e SXescoreALTO, respectivamente (p <
0,001). Morte por todas as causas foi significativamente mais frequente no grupo
de SXescoreALTO comparado ao grupo 'sem DAC significativa', 16,7% e 3,8% (p <
0,001), respectivamente. Apos ajuste para fatores de confusao, todos os desfechos
permaneceram associados com o SXescore. Conclusao:: O SXescore prediz
independentemente MACE em pacientes submetidos a cineangiocoronariografia
diagnostica. Seu uso rotineiro nesse contexto poderia identificar pacientes de
pior prognostico.
PMID- 27509093
TI - Relationship Between Neck Circumference and Epicardial Fat Thickness in a Healthy
Male Population.
AB - Background:: Epicardial fat is an upper body visceral fat depot that may play a
significant role in the development of adverse metabolic and cardiovascular risk
profiles. There is a significant direct relationship between the amount of
epicardial fat and general body adiposity (body mass index, BMI), but data
regarding subcutaneous adiposity is limited. Objective:: We conducted a study to
determine the association between neck circumference and epicardial fat thickness
in healthy young male individuals, and assess their individual correlations with
general body adiposity and cardiometabolic risk factors. Methods:: One hundred
consecutive male patients aged 18 years or older with no known major medical
conditions were included in the study. All participants underwent detailed
physical examination including measurement of blood pressure, weight, height,
waist/hip ratio, and neck circumference. Blood was collected to determine fasting
glucose and lipid parameters. A standard echocardiographic examination was
performed with additional epicardial fat thickness determination. Results:: Among
100 study participants, neck circumference correlated significantly with weight,
waist circumference, BMI, blood glucose, serum total cholesterol, low-density
(LDL)-cholesterol, and triglycerides levels. No significant correlation was found
between neck circumference and high-density lipoprotein (HDL)-cholesterol levels.
Neck circumference correlated moderately and positively with echocardiographic
epicardial fat thickness. Conclusion:: Among patients with low cardiometabolic
risk, increased neck circumference was associated with increased epicardial fat
thickness. Fundamentos:: A gordura epicardica e um deposito de gordura visceral
na parte superior do organismo que pode desempenhar um papel importante no
desenvolvimento de perfis cardiovasculares e metabolicos adversos. Ha uma relacao
direta significativa entre a quantidade de gordura epicardica e a adiposidade
corporal geral (indice de massa corporal, IMC), mas dados sobre a adiposidade
subcutanea sao limitados. Objetivos:: Realizamos um estudo para determinar a
associacao entre a circunferencia do pescoco e a espessura da gordura epicardica
em jovens saudaveis do sexo masculino, alem de avaliar as suas correlacoes
individuais com a adiposidade corporal geral e fatores de risco
cardiometabolicos. Metodos:: Cem pacientes consecutivos do sexo masculino com
idade igual ou superior a 18 anos e sem nenhuma condicao medica importante e
conhecida foram incluidos no estudo. Todos os participantes foram submetidos a um
exame fisico detalhado que incluiu medida da pressao arterial, peso, altura,
razao cintura/quadril e circunferencia do pescoco. Sangue foi coletado para
determinacao da glicemia de jejum e parametros lipidicos. Um exame
ecocardiografico padrao foi realizado com determinacao adicional da espessura da
gordura epicardica. Resultados:: Entre os 100 participantes do estudo, a
circunferencia do pescoco mostrou correlacao significativa com o peso,
circunferencia de cintura, IMC, glicemia e niveis sericos de colesterol total,
lipoproteina de baixa densidade (LDL-colesterol) e triglicerideos. Nao foi
observada correlacao significativa entre a circunferencia do pescoco e niveis de
colesterol de alta densidade (HDL-colesterol). A circunferencia do pescoco
correlacionou moderadamente e positivamente com a espessura da gordura epicardica
a ecocardiografia. Conclusao:: Entre pacientes com baixo risco cardiometabolico,
o aumento da circunferencia do pescoco foi associado a um aumento da espessura da
gordura epicardica.
PMID- 27509094
TI - Until Death Do Us Part.
PMID- 27509095
TI - New World and Old World Alphaviruses Have Evolved to Exploit Different Components
of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral Replication
Complexes.
AB - The positive-strand RNA viruses initiate their amplification in the cell from a
single genome delivered by virion. This single RNA molecule needs to become
involved in replication process before it is recognized and degraded by cellular
machinery. In this study, we show that distantly related New World and Old World
alphaviruses have independently evolved to utilize different cellular stress
granule-related proteins for assembly of complexes, which recruit viral genomic
RNA and facilitate formation of viral replication complexes (vRCs). Venezuelan
equine encephalitis virus (VEEV) utilizes all members of the Fragile X syndrome
(FXR) family, while chikungunya and Sindbis viruses exploit both members of the
G3BP family. Despite being in different families, these proteins share common
characteristics, which determine their role in alphavirus replication, namely,
the abilities for RNA-binding and for self-assembly into large structures. Both
FXR and G3BP proteins interact with virus-specific, repeating amino acid
sequences located in the C-termini of hypervariable, intrinsically disordered
domains (HVDs) of viral nonstructural protein nsP3. We demonstrate that these
host factors orchestrate assembly of vRCs and play key roles in RNA and virus
replication. Only knockout of all of the homologs results in either pronounced or
complete inhibition of replication of different alphaviruses. The use of multiple
homologous proteins with redundant functions mediates highly efficient
recruitment of viral RNA into the replication process. This independently evolved
acquisition of different families of cellular proteins by the disordered protein
fragment to support alphavirus replication suggests that other RNA viruses may
utilize a similar mechanism of host factor recruitment for vRC assembly. The use
of different host factors by alphavirus species may be one of the important
determinants of their pathogenesis.
PMID- 27509096
TI - Domino [Pd]-Catalysis: One-Pot Synthesis of Isobenzofuran-1(3H)-ones.
AB - An efficient domino [Pd]-catalysis for the synthesis of isobenzofuran-1(3H)-ones
is presented. The strategy shows broad substrate scope and is amenable to o
bromobenzyl tertiary/secondary/primary alcohols. Significantly, the method was
applied to the synthesis of antiplatelet drug n-butyl phthalide and cytotoxic
agonist 3a-[4'-methoxylbenzyl]-5,7-dimethoxyphthalide.
PMID- 27509097
TI - The Emergence of the Randomized, Controlled Trial.
PMID- 27509098
TI - The DNR Order after 40 Years.
PMID- 27509099
TI - Coming Back from the Dead.
PMID- 27509101
TI - Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome.
AB - BACKGROUND: The transfer of fresh embryos is generally preferred over the
transfer of frozen embryos for in vitro fertilization (IVF), but some evidence
suggests that frozen-embryo transfer may improve the live-birth rate and lower
the rates of the ovarian hyperstimulation syndrome and pregnancy complications in
women with the polycystic ovary syndrome. METHODS: In this multicenter trial, we
randomly assigned 1508 infertile women with the polycystic ovary syndrome who
were undergoing their first IVF cycle to undergo either fresh-embryo transfer or
embryo cryopreservation followed by frozen-embryo transfer. After 3 days of
embryo development, women underwent the transfer of up to two fresh or frozen
embryos. The primary outcome was a live birth after the first embryo transfer.
RESULTS: Frozen-embryo transfer resulted in a higher frequency of live birth
after the first transfer than did fresh-embryo transfer (49.3% vs. 42.0%), for a
rate ratio of 1.17 (95% confidence interval [CI], 1.05 to 1.31; P=0.004). Women
who underwent frozen-embryo transfer also had a lower frequency of pregnancy loss
(22.0% vs. 32.7%), for a rate ratio of 0.67 (95% CI, 0.54 to 0.83; P<0.001), and
of the ovarian hyperstimulation syndrome (1.3% vs. 7.1%), for a rate ratio of
0.19 (95% CI, 0.10 to 0.37; P<0.001), but a higher frequency of preeclampsia
(4.4% vs. 1.4%), for a rate ratio of 3.12 (95% CI, 1.26 to 7.73; P=0.009). There
were no significant between-group differences in rates of other pregnancy and
neonatal complications. There were five neonatal deaths in the frozen-embryo
group and none in the fresh-embryo group (P=0.06). CONCLUSIONS: Among infertile
women with the polycystic ovary syndrome, frozen-embryo transfer was associated
with a higher rate of live birth, a lower risk of the ovarian hyperstimulation
syndrome, and a higher risk of preeclampsia after the first transfer than was
fresh-embryo transfer. (Funded by the National Basic Research Program of China
and others; ClinicalTrials.gov number, NCT01841528.).
PMID- 27509103
TI - Raynaud's Phenomenon.
PMID- 27509102
TI - Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.
AB - BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal alpha
galactosidase deficiency, leads to substrate accumulation in multiple organs.
Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of
alpha-galactosidase, increasing enzyme trafficking to lysosomes. METHODS: The
initial assay of mutant alpha-galactosidase forms that we used to categorize 67
patients with Fabry's disease for randomization to 6 months of double-blind
migalastat or placebo (stage 1), followed by open-label migalastat from 6 to 12
months (stage 2) plus an additional year, had certain limitations. Before
unblinding, a new, validated assay showed that 50 of the 67 participants had
mutant alpha-galactosidase forms suitable for targeting by migalastat. The
primary end point was the percentage of patients who had a response (>=50%
reduction in the number of globotriaosylceramide inclusions per kidney
interstitial capillary) at 6 months. We assessed safety along with disease
substrates and renal, cardiovascular, and patient-reported outcomes. RESULTS: The
primary end-point analysis, involving patients with mutant alpha-galactosidase
forms that were suitable or not suitable for migalastat therapy, did not show a
significant treatment effect: 13 of 32 patients (41%) who received migalastat and
9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30).
Among patients with suitable mutant alpha-galactosidase who received migalastat
for up to 24 months, the annualized changes from baseline in the estimated
glomerular filtration rate (GFR) and measured GFR were -0.30+/-0.66 and -1.51+/
1.33 ml per minute per 1.73 m(2) of body-surface area, respectively. The left
ventricular-mass index decreased significantly from baseline (-7.7 g per square
meter; 95% confidence interval [CI], -15.4 to -0.01), particularly when left
ventricular hypertrophy was present (-18.6 g per square meter; 95% CI, -38.2 to
1.0). The severity of diarrhea, reflux, and indigestion decreased. CONCLUSIONS:
Among all randomly assigned patients (with mutant alpha-galactosidase forms that
were suitable or not suitable for migalastat therapy), the percentage of patients
who had a response at 6 months did not differ significantly between the
migalastat group and the placebo group. (Funded by Amicus Therapeutics;
ClinicalTrials.gov numbers, NCT00925301 [study AT1001-011] and NCT01458119 [study
AT1001-041].).
PMID- 27509104
TI - IMAGES IN CLINICAL MEDICINE. Aortic Calcification and Superior-Mesenteric-Artery
Stenosis.
PMID- 27509105
TI - CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 24-2016. A 66-Year-Old
Man with Malaise, Weakness, and Hypercalcemia.
PMID- 27509106
TI - RetroSternal--Looking Back at Thymectomy for Myasthenia Gravis.
PMID- 27509100
TI - Randomized Trial of Thymectomy in Myasthenia Gravis.
AB - BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis,
but there is no conclusive evidence of its benefit. We conducted a multicenter,
randomized trial comparing thymectomy plus prednisone with prednisone alone.
METHODS: We compared extended transsternal thymectomy plus alternate-day
prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age
who had generalized nonthymomatous myasthenia gravis with a disease duration of
less than 5 years were included if they had Myasthenia Gravis Foundation of
America clinical class II to IV disease (on a scale from I to V, with higher
classes indicating more severe disease) and elevated circulating concentrations
of acetylcholine-receptor antibody. The primary outcomes were the time-weighted
average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with
higher scores indicating more severe disease) over a 3-year period, as assessed
by means of blinded rating, and the time-weighted average required dose of
prednisone over a 3-year period. RESULTS: A total of 126 patients underwent
randomization between 2006 and 2012 at 36 sites. Patients who underwent
thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score
over a 3-year period than those who received prednisone alone (6.15 vs. 8.99,
P<0.001); patients in the thymectomy group also had a lower average requirement
for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the
thymectomy group than in the prednisone-only group required immunosuppression
with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations
(9% vs. 37%, P<0.001). The number of patients with treatment-associated
complications did not differ significantly between groups (P=0.73), but patients
in the thymectomy group had fewer treatment-associated symptoms related to
immunosuppressive medications (P<0.001) and lower distress levels related to
symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3
year period in patients with nonthymomatous myasthenia gravis. (Funded by the
National Institute of Neurological Disorders and Stroke and others; MGTX
ClinicalTrials.gov number, NCT00294658.).
PMID- 27509107
TI - "Freeze Only"--An Evolving Standard in Clinical In Vitro Fertilization.
PMID- 27509108
TI - After Ebola in West Africa--Unpredictable Risks, Preventable Epidemics.
PMID- 27509109
TI - Fusion Surgery for Lumbar Spinal Stenosis.
PMID- 27509110
TI - Fusion Surgery for Lumbar Spinal Stenosis.
PMID- 27509111
TI - Fusion Surgery for Lumbar Spinal Stenosis.
PMID- 27509112
TI - Fusion Surgery for Lumbar Spinal Stenosis.
PMID- 27509113
TI - Fusion Surgery for Lumbar Spinal Stenosis.
PMID- 27509114
TI - Stenting versus Surgery for Carotid Stenosis.
PMID- 27509115
TI - Stenting versus Surgery for Carotid Stenosis.
PMID- 27509116
TI - Stenting versus Surgery for Carotid Stenosis.
PMID- 27509117
TI - Stenting versus Surgery for Carotid Stenosis.
PMID- 27509118
TI - Stenting versus Surgery for Carotid Stenosis.
PMID- 27509119
TI - Newborn Bilirubin Screening for Biliary Atresia.
PMID- 27509120
TI - Cervical Pessary and Preterm Singleton Birth.
PMID- 27509121
TI - Cervical Pessary and Preterm Singleton Birth.
PMID- 27509122
TI - IMAGES IN CLINICAL MEDICINE. Enlarged Right Atrium.
PMID- 27509123
TI - INTERACTIVE MEDICAL CASE. Tracing the Cause of Abdominal Pain.
PMID- 27509124
TI - Assessment of Minimal Residual Disease in Standard-Risk AML.
PMID- 27509125
TI - Assessment of Minimal Residual Disease in Standard-Risk AML.
PMID- 27509126
TI - Assessment of Minimal Residual Disease in Standard-Risk AML.
PMID- 27509127
TI - Assessment of Minimal Residual Disease in Standard-Risk AML.
PMID- 27509128
TI - miR-6734 Up-Regulates p21 Gene Expression and Induces Cell Cycle Arrest and
Apoptosis in Colon Cancer Cells.
AB - Recently, microRNAs have been implicated in the regulation of gene expression in
terms of both gene silencing and gene activation. Here, we investigated the
effects of miR-6734, which has a sequence homology with a specific region of
p21WAF1/CIP1 (p21) promoter, on cancer cell growth and the mechanisms involved in
this effect. miR-6734 up-regulated p21 expression at both mRNA and protein levels
and chromatin immunoprecipitation analysis using biotin-labeled miR-6734
confirmed the association of miR-6734 with p21 promoter. Moreover, miR-6734
inhibited cancer cell growth and induced cell cycle arrest and apoptosis in HCT
116 cells, which was abolished by knockdown of p21. The phosphorylation of Rb and
the cleavage of caspase 3 and PARP were suppressed by miR-6734 transfection in
HCT-116 cells and these effects were also reversed by p21 knockdown. In addition,
miR-6734 transfection caused prolonged induction of p21 gene and modification of
histones in p21 promoter, which are typical aspects of a phenomenon referred to
as RNA activation (RNAa). Collectively, our results demonstrated that miR-6734
inhibits the growth of colon cancer cells by up-regulating p21 gene expression
and subsequent induction of cell cycle arrest and apoptosis, suggesting its role
as an important endogenous regulator of cancer cell proliferation and survival.
PMID- 27509129
TI - A Triangle Mesh Standardization Method Based on Particle Swarm Optimization.
AB - To enhance the triangle quality of a reconstructed triangle mesh, a novel
triangle mesh standardization method based on particle swarm optimization (PSO)
is proposed. First, each vertex of the mesh and its first order vertices are
fitted to a cubic curve surface by using least square method. Additionally, based
on the condition that the local fitted surface is the searching region of PSO and
the best average quality of the local triangles is the goal, the vertex position
of the mesh is regulated. Finally, the threshold of the normal angle between the
original vertex and regulated vertex is used to determine whether the vertex
needs to be adjusted to preserve the detailed features of the mesh. Compared with
existing methods, experimental results show that the proposed method can
effectively improve the triangle quality of the mesh while preserving the
geometric features and details of the original mesh.
PMID- 27509130
TI - A Causal Role for the Cortical Frontal Eye Fields in Microsaccade Deployment.
AB - Microsaccades aid vision by helping to strategically sample visual scenes.
Despite the importance of these small eye movements, no cortical area has ever
been implicated in their generation. Here, we used unilateral and bilateral
reversible inactivation of the frontal eye fields (FEF) to identify a cortical
drive for microsaccades. Unexpectedly, FEF inactivation altered microsaccade
metrics and kinematics. Such inactivation also impaired microsaccade deployment
following peripheral cue onset, regardless of cue side or inactivation
configuration. Our results demonstrate that the FEF provides critical top-down
drive for microsaccade generation, particularly during the recovery of
microsaccades after disruption by sensory transients. Our results constitute the
first direct evidence, to our knowledge, for the contribution of any cortical
area to microsaccade generation, and they provide a possible substrate for how
cognitive processes can influence the strategic deployment of microsaccades.
PMID- 27509132
TI - Functional Blood Progenitor Markers in Developing Human Liver Progenitors.
AB - In the early fetal liver, hematopoietic progenitors expand and mature together
with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes.
Previous analyses of human fetal livers indicated that both progenitors support
each other's lineage maturation and curiously share some cell surface markers
including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we
demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells)
transition through a progenitor stage expressing CD34 and CD133 as well as GATA2,
an additional hematopoietic marker that has not previously been associated with
human hepatoblast development. Dynamic expression patterns for CD34, CD133, and
GATA2 in hepatoblasts were validated in human fetal livers collected from the
first and second trimesters of gestation. Knockdown experiments demonstrate that
each gene also functions to regulate hepatic fate mostly in a cell-autonomous
fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers
in human liver progenitors.
PMID- 27509131
TI - A Putative Association of a Single Nucleotide Polymorphism in GPR126 with
Aggressive Periodontitis in a Japanese Population.
AB - Periodontitis is an inflammatory disease causing loss of tooth-supporting
periodontal tissue. Disease susceptibility to the rapidly progressive form of
periodontitis, aggressive periodontitis (AgP), appears to be influenced by
genetic risk factors. To identify these in a Japanese population, we performed
whole exome sequencing of 41 unrelated generalized or localized AgP patients. We
found that AgP is putatively associated with single nucleotide polymorphism (SNP)
rs536714306 in the G-protein coupled receptor 126 gene, GPR126 [c.3086 G>A
(p.Arg1029Gln)]. Since GPR126 activates the cAMP/PKA signaling pathway, we
performed cAMP ELISA analysis of cAMP concentrations, and found that rs536714306
impaired the signal transactivation of GPR126. Moreover, transfection of human
periodontal ligament (HPDL) cells with wild-type or mutant GPR126 containing
rs536714306 showed that wild-type GPR126 significantly increased the mRNA
expression of bone sialoprotein, osteopontin, and Runx2 genes, while mutant
GPR126 had no effect on the expression of these calcification-related genes. The
increase in expression of these genes was through the GPR126-induced increase of
bone morphogenic protein-2, inhibitor of DNA binding (ID) 2, and ID4 expression.
These data indicate that GPR126 might be important in maintaining the homeostasis
of periodontal ligament tissues through regulating the cytodifferentiation of
HPDL cells. The GPR126 SNP rs536714306 negatively influences this homeostasis,
leading to the development of AgP, suggesting that it is a candidate genetic risk
factor for AgP in the Japanese population.
PMID- 27509133
TI - Integrin-Associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells
from Apoptosis, Detachment, and Differentiation.
AB - Human embryonic stem cells (hESCs) can be maintained in a fully defined niche on
extracellular matrix substrates, to which they attach through integrin receptors.
However, the underlying integrin signaling mechanisms, and their contribution to
hESC behavior, are largely unknown. Here, we show that focal adhesion kinase
(FAK) transduces integrin activation and supports hESC survival, substrate
adhesion, and maintenance of the undifferentiated state. After inhibiting FAK
kinase activity we show that hESCs undergo cell detachment-dependent apoptosis or
differentiation. We also report deactivation of FAK downstream targets, AKT and
MDM2, and upregulation of p53, all key players in hESC regulatory networks. Loss
of integrin activity or FAK also induces cell aggregation, revealing a role in
the cell-cell interactions of hESCs. This study provides insight into the
integrin signaling cascade activated in hESCs and reveals in FAK a key player in
the maintenance of hESC survival and undifferentiated state.
PMID- 27509134
TI - Embryonic Stem Cell Culture Conditions Support Distinct States Associated with
Different Developmental Stages and Potency.
AB - Embryonic stem cells (ESCs) are cell lines derived from the mammalian pre
implantation embryo. Here we assess the impact of derivation and culture
conditions on both functional potency and ESC transcriptional identity.
Individual ESCs cultured in either two small-molecule inhibitors (2i) or with
knockout serum replacement (KOSR), but not serum, can generate high-level
chimeras regardless of how these cells were derived. ESCs cultured in these
conditions showed a transcriptional correlation with early pre-implantation
embryos (E1.5-E3.5) and contributed to development from the 2-cell stage.
Conversely, the transcriptome of serum-cultured ESCs correlated with later stages
of development (E4.5), at which point embryonic cells are more restricted in
their developmental potential. Thus, ESC culture systems are not equivalent, but
support cell types that resemble distinct developmental stages. Cells derived in
one condition can be reprogrammed to another developmental state merely by
adaptation to another culture condition.
PMID- 27509135
TI - MIF Plays a Key Role in Regulating Tissue-Specific Chondro-Osteogenic
Differentiation Fate of Human Cartilage Endplate Stem Cells under Hypoxia.
AB - Degenerative cartilage endplate (CEP) shows decreased chondrification and
increased ossification. Cartilage endplate stem cells (CESCs), with the capacity
for chondro-osteogenic differentiation, are responsible for CEP restoration. CEP
is avascular and hypoxic, while the physiological hypoxia is disrupted in the
degenerated CEP. Hypoxia promoted chondrogenesis but inhibited osteogenesis in
CESCs. This tissue-specific differentiation fate of CESCs in response to hypoxia
was physiologically significant with regard to CEP maintaining chondrification
and refusing ossification. MIF, a downstream target of HIF1A, is involved in
cartilage and bone metabolisms, although little is known about its regulatory
role in differentiation. In CESCs, MIF was identified as a key point through
which HIF1A regulated the chondro-osteogenic differentiation. Unexpectedly,
unlike the traditionally recognized mode, increased nuclear-expressed MIF under
hypoxia was identified to act as a transcriptional regulator by interacting with
the promoter of SOX9 and RUNX2. This mode of HIF1A/MIF function may represent a
target for CEP degeneration therapy.
PMID- 27509136
TI - Cell-Surface Protein Profiling Identifies Distinctive Markers of Progenitor Cells
in Human Skeletal Muscle.
AB - Skeletal muscle contains two distinct stem/progenitor populations. One is the
satellite cell, which acts as a muscle stem cell, and the other is the
mesenchymal progenitor, which contributes to muscle pathogeneses such as fat
infiltration and fibrosis. Detailed and accurate characterization of these
progenitors in humans remains elusive. Here, we performed comprehensive cell
surface protein profiling of the two progenitor populations residing in human
skeletal muscle and identified three previously unrecognized markers: CD82 and
CD318 for satellite cells and CD201 for mesenchymal progenitors. These markers
distinguish myogenic and mesenchymal progenitors, and enable efficient isolation
of the two types of progenitors. Functional study revealed that CD82 ensures
expansion and preservation of myogenic progenitors by suppressing excessive
differentiation, and CD201 signaling favors adipogenesis of mesenchymal
progenitors. Thus, cell-surface proteins identified here are not only useful
markers but also functionally important molecules, and provide valuable insight
into human muscle biology and diseases.
PMID- 27509137
TI - The Luteinizing Hormone-Testosterone Pathway Regulates Mouse Spermatogonial Stem
Cell Self-Renewal by Suppressing WNT5A Expression in Sertoli Cells.
AB - Spermatogenesis originates from self-renewal of spermatogonial stem cells (SSCs).
Previous studies have reported conflicting roles of gonadotropic pituitary
hormones in SSC self-renewal. Here, we explored the role of hormonal regulation
of SSCs using Fshb and Lhcgr knockout (KO) mice. Although follicle-stimulating
hormone (FSH) is thought to promote self-renewal by glial cell line-derived
neurotrophic factor (GDNF), no abnormalities were found in SSCs and their
microenvironment. In contrast, SSCs were enriched in Lhcgr-deficient mice.
Moreover, wild-type SSCs transplanted into Lhcgr-deficient mice showed enhanced
self-renewal. Microarray analysis revealed that Lhcgr-deficient testes have
enhanced WNT5A expression in Sertoli cells, which showed an immature phenotype.
Since WNT5A was upregulated by anti-androgen treatment, testosterone produced by
luteinizing hormone (LH) is required for Sertoli cell maturation. WNT5A promoted
SSC activity both in vitro and in vivo. Therefore, FSH is not responsible for
GDNF regulation, while LH negatively regulates SSC self-renewal by suppressing
WNT5A via testosterone.
PMID- 27509138
TI - A Method to Identify and Isolate Pluripotent Human Stem Cells and Mouse Epiblast
Stem Cells Using Lipid Body-Associated Retinyl Ester Fluorescence.
PMID- 27509139
TI - Factors affecting adaptation to the role of motherhood in mothers of preterm
infants admitted to the neonatal intensive care unit: a qualitative study.
AB - AIM: The aim of this study was to explore factors affecting adaptation to the
role of motherhood in mothers of preterm infants admitted to the neonatal
intensive care unit. BACKGROUND: Transition to motherhood often causes
significant issues in terms of adaptation to the role of motherhood. The main
factors leading to parental stress, especially in the neonatal intensive care
unit, have shown that the greatest source of stress is the loss of women's role
as mothers. DESIGN: It was a qualitative study with content analysis approach.
METHODS: Semi-structured in-depth interviews were used for data collection.
Interviews were conducted with 17 mothers of preterm infants (under 36 weeks) who
had been hospitalized for at least one week in the neonatal intensive care unit.
Purposive sampling with maximum diversity was used to recruit mothers in
Kermanshah province (west of Iran). Data was collected during 2013-2014.
Interviews were recorded and transcribed verbatim. Data were analysed using
conventional content analysis. FINDINGS: Explanation of the mothers' perspective
towards factors affecting adaptation to the role of motherhood led to two main
categories of individual factors (emotional distress, self-efficacy, interaction
and alienation) and social factors (support, prejudice). CONCLUSION: Adaptation
to the role of motherhood can be promoted through supporting mothers of preterm
infants, empowering them and increasing their self-efficacy, to eliminate
negative factors and emotions.
PMID- 27509140
TI - [Not Available].
PMID- 27509141
TI - Postoperative Foot Massage for Patients after Caesarean Delivery.
AB - OBJECTIVE: Little evidence is available on complementary therapies for anxiety
and pain relief after caesarean delivery. The purpose of this study was to
evaluate the effects of foot massage post-operatively in patients after caesarean
delivery. MATERIALS AND METHODS: 70 patients were divided to the study or control
group after cesarean delivery. Patients in the study group had foot massages for
20 min after surgery. All patients underwent heart rate variability analysis
(HRV) and scored their anxiety; pain intensity was evaluated using an 11-point
numerical rating scale (NRS). RESULTS: In the study group the HRV, as measured by
the low frequency power (LF) value and the LF-to-high frequency power (LF/HF)
ratio during Holter assessment, was significantly less after foot massage
intervention, but was not changed in the control group. Moreover, the HF value
significantly increased and the anxiety score significantly decreased after foot
massage intervention, but not in the control group. The pain intensity score
obtained 60 min after the massage was significantly lower in the study group than
the control group, as were the vital signs (respiratory rate, and systolic and
diastolic blood pressure). CONCLUSION: Post-operative massage intervention can
reduce anxiety and pain in patients after caesarean delivery.
PMID- 27509142
TI - Grape Pomace, an Agricultural Byproduct Reducing Mycotoxin Absorption: In Vivo
Assessment in Pig Using Urinary Biomarkers.
AB - The efficacy of four agricultural byproducts (ABPs) and two commercial binders
(CBs) to reduce the gastrointestinal absorption of a mixture of mycotoxins was
tested in piglets using urinary mycotoxin biomarkers as indicator of the absorbed
mycotoxins. Twenty-eight piglets were administered a bolus contaminated with the
mycotoxin mixture containing or not ABP or CB. Twenty-four hour urine was
collected and analyzed for mycotoxin biomarkers by using a multiantibody
immunoaffinity-based LC-MS/MS method. Each bolus contained 769 MUg of fumonisin
B1 (FB1), 275 MUg of deoxynivalenol (DON), 29 MUg of zearalenone (ZEN), 6.5 MUg
of aflatoxin B1 (AFB1) and 6.6 MUg of ochratoxin A (OTA) corresponding to 2.2,
0.8, 0.08, 0.02, and 0.02 MUg/g in the daily diet, respectively. The percentage
of ABP in each bolus was 50%, whereas for the two CBs the percentages were 5.2
and 17%, corresponding to 2.8, 0.3, and 0.9% in the daily diet, respectively. The
reduction of mycotoxin absorption was up to 69 and 54% for ABPs and CBs,
respectively. White grape pomace of Malvasia was the most effective material as
it reduced significantly (p < 0.05) urinary mycotoxin biomarker of AFB1 (67%) and
ZEN (69%), whereas reductions statistically not significant were observed for FB1
(57%), DON (40%), and OTA (27%). This study demonstrates that grape pomace
reduces the gastrointestinal absorption of mycotoxins. This agricultural
byproduct can be considered an alternative to commercial products and used in the
feed industries as an effective, cheap, and natural binder for multiple
mycotoxins.
PMID- 27509143
TI - Effectiveness of Phosphodiesterase 5 Inhibitors in the Treatment of Erectile
Dysfunction in Patients with Spinal Cord Trauma: Systematic Review and Meta
Analysis.
AB - OBJECTIVE: To determine the effectiveness of the Phosphodiesterase 5 (PDE5)
Inhibitors for the treatment of erectile dysfunction in patients with spinal
trauma. METHODS: A systematic review and meta-analysis comparing PDE5 inhibitors
versus placebo were carried out for clinical trials conducted between 1980 and
2014 that evaluated male patients older than 18 years, diagnosed with spinal cord
trauma and erectile dysfunction. We designed a search strategy for Medline,
CENTRAL, EMBASE and other electronic sources. Two investigators independently and
blindly screened the studies for inclusion. A random effect meta-analysis was
performed. RESULTS: Six studies involving 963 patients were included. Male
patients over 18 years with ED attributable or subsequent to traumatic spinal
cord injury (SCI) were included from these studies. In 4 of these studies,
patients were randomized to the treatment group receiving sildenafil and the
comparison group was placebo. Out of the remaining 2 trials, one compared
tadalafil against the placebo and the other vardenafil versus placebo. The
improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean
difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%).
CONCLUSIONS: PDE5 inhibitors are effective for the treatment of erectile
dysfunction secondary to SCI.
PMID- 27509145
TI - American Thoracic Society and Marron Institute Report. Estimated Excess Morbidity
and Mortality Caused by Air Pollution above American Thoracic Society-Recommended
Standards, 2011-2013.
AB - Estimates of the health impacts of air pollution are needed to make informed air
quality management decisions at both the national and local levels. Using design
values of ambient pollution concentrations from 2011-2013 as a baseline, the
American Thoracic Society (ATS) and the Marron Institute of Urban Management
estimated excess morbidity and mortality in the United States attributable to
exposure to ambient ozone (O3) and fine particulate matter (PM2.5) at levels
above the American Thoracic Society-recommended standards. Within the subset of
counties with valid design values for each pollutant, 14% had PM2.5
concentrations greater than the ATS recommendation, whereas 91% had O3
concentrations greater than the ATS recommendation. Approximately 9,320 excess
deaths (69% from O3; 31% from PM2.5), 21,400 excess morbidities (74% from O3; 26%
from PM2.5), and 19,300,000 adversely impacted days (88% from O3; 12% from PM2.5)
in the United States each year are attributable to pollution exceeding the ATS
recommended standards. California alone is responsible for 37% of the total
estimated health impacts, and the next three states (Pennsylvania, Texas, and
Ohio) together contributed to 20% of the total estimates. City-specific health
estimates are provided in this report and through an accompanying online tool to
help inform air quality management decisions made at the local level. Riverside
and Los Angeles, California have the most to gain by attaining the ATS
recommendations for O3 and PM2.5. This report will be revised and updated
regularly to help cities track their progress.
PMID- 27509146
TI - Changing the Climate of Respiratory Clinical Practice. Insights from the 2016
Climate and Health Assessment of the U.S. Global Change Research Program.
PMID- 27509144
TI - Lymphoblastoid Cell Lines as a Tool to Study Inter-Individual Differences in the
Response to Glucose.
AB - BACKGROUND: White blood cells have been shown in animal studies to play a central
role in the pathogenesis of diabetic retinopathy. Lymphoblastoid cells are
immortalized EBV-transformed primary B-cell leukocytes that have been extensively
used as a model for conditions in which white blood cells play a primary role.
The purpose of this study was to investigate whether lymphoblastoid cell lines,
by retaining many of the key features of primary leukocytes, can be induced with
glucose to demonstrate relevant biological responses to those found in diabetic
retinopathy. METHODS: Lymphoblastoid cell lines were obtained from twenty-three
human subjects. Differences between high and standard glucose conditions were
assessed for expression, endothelial adhesion, and reactive oxygen species.
RESULTS: Collectively, stimulation of the lymphoblastoid cell lines with high
glucose demonstrated corresponding changes on molecular, cellular and functional
levels. Lymphoblastoid cell lines up-regulated expression of a panel of genes
associated with the leukocyte-mediated inflammation found in diabetic retinopathy
that include: a cytokine (IL-1B fold change = 2.11, p-value = 0.02), an enzyme
(PKCB fold change = 2.30, p-value = 0.01), transcription factors (NFKB-p50 fold
change = 2.05, p-value = 0.01), (NFKB-p65 fold change = 2.82, p-value = 0.003),
and an adhesion molecule (CD18 fold change = 2.59, 0.02). Protein expression of
CD18 was also increased (p-value = 2.14x10-5). The lymphoblastoid cell lines
demonstrated increased adhesiveness to endothelial cells (p = 1.28x10-5).
Reactive oxygen species were increased (p = 2.56x10-6). Significant inter
individual variation among the lymphoblastoid cell lines in these responses was
evident (F = 18.70, p < 0.0001). CONCLUSIONS: Exposure of lymphoblastoid cell
lines derived from different human subjects to high glucose demonstrated
differential and heterogeneous gene expression, adhesion, and cellular effects
that recapitulated features found in the diabetic state. Lymphoblastoid cells may
represent a useful tool to guide an individualized understanding of the
development and potential treatment of diabetic complications like retinopathy.
PMID- 27509147
TI - The Global Emergence of Unregulated Stem Cell Treatments for Respiratory
Diseases. Professional Societies Need to Act.
PMID- 27509148
TI - Improving Health Literacy. The New American Thoracic Society Guidelines for
Patient Education Materials.
PMID- 27509149
TI - Acute Chest Syndrome, Asthma, and Lung Function in Sickle Cell Disease. Which Is
the Chicken, and Which Is the Egg?
PMID- 27509150
TI - The Power and Importance of Accommodation for Communication Impairment in the
Intensive Care Unit.
PMID- 27509151
TI - Go Big: Measuring and Tackling Psychological Morbidity after Critical Illness.
PMID- 27509152
TI - Broken Wings and Resilience after Critical Illness.
PMID- 27509153
TI - Incretins and Insulin Resistance in Obstructive Sleep Apnea. Chicken or the Egg?
PMID- 27509155
TI - A 62-Year-Old Man with Cough and Dyspnea after Crack Cocaine Inhalation.
PMID- 27509154
TI - Sarcoidosis in America. Analysis Based on Health Care Use.
AB - RATIONALE: There have been no recent comprehensive studies of the epidemiology of
sarcoidosis in the United States. Changes in health care use have made available
access to data on large numbers of patients with sarcoidosis. OBJECTIVES: To use
a U.S. national health care database to gather data on patients with sarcoidosis
identified over a 3-year period who were 18 years of age and older, and to
determine health care costs for these patients. METHODS: The Optum health care
database was queried for a 3-year period (2010-2013). This database includes
approximately 15% of U.S. residents. The incidence rate of sarcoidosis was
calculated for new cases identified in each year. Calculation of prevalence was
based on any patient with sarcoidosis seen during the year. Incidence and
prevalence rates are reported per 100,000 patients. MEASUREMENTS AND MAIN
RESULTS: A total of 29,372 adult patients with sarcoidosis were identified. Of
these, 14,700 (55%) were over 55 years of age at the time of diagnosis. The
incidence and prevalence rates were higher for African Americans (17.8 and 141.4
per 100,000, respectively) than for white individuals (8.1 and 49.8), Hispanics
(4.3 and 21.7), or Asians (3.2 and 18.9). Women were two times more likely to
have sarcoidosis, with the highest prevalence for sarcoidosis noted in African
American women (178.5). Overall, the yearly health care cost reported for
patients with sarcoidosis was low, with a median of $18,663 per year. However,
the yearly cost for the top 5% was $93,201. CONCLUSIONS: For patients 18 years of
age and older enrolled in a U.S. national administrative database, sarcoidosis
was more common among African Americans, but it was reported for all four of the
major ethnic groups studied. While health care costs were relatively small for
most patients, the cost of care for some patients was considerable.
PMID- 27509156
TI - Dyspnea and an Arteriovenous Fistula.
PMID- 27509157
TI - Nodular Pleural Thickening after Lobectomy for Lung Cancer. Insights on Imaging
of the Pleura.
PMID- 27509158
TI - Long-Term Effects of Bronchial Thermoplasty on Airway Smooth Muscle and Reticular
Basement Membrane Thickness in Severe Asthma.
PMID- 27509159
TI - The Real Face of Borderline Pulmonary Hypertension in Connective Tissue Disease.
PMID- 27509160
TI - Severe Colitis Associated with Pirfenidone Use in Idiopathic Pulmonary Fibrosis.
PMID- 27509161
TI - Reply: Indwelling Tunneled Pleural Catheters for the Management of Hepatic
Hydrothorax: A Word of Caution.
PMID- 27509162
TI - Indwelling Tunneled Pleural Catheters for the Management of Hepatic Hydrothorax:
A Word of Caution.
PMID- 27509163
TI - An Official American Thoracic Society Workshop Report 2015. Stem Cells and Cell
Therapies in Lung Biology and Diseases.
AB - The University of Vermont College of Medicine, in collaboration with the NHLBI,
Alpha-1 Foundation, American Thoracic Society, Cystic Fibrosis Foundation,
European Respiratory Society, International Society for Cellular Therapy, and the
Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell
Therapies in Lung Biology and Lung Diseases," held July 27 to 30, 2015, at the
University of Vermont. The conference objectives were to review the current
understanding of the role of stem and progenitor cells in lung repair after
injury and to review the current status of cell therapy and ex vivo
bioengineering approaches for lung diseases. These are all rapidly expanding
areas of study that both provide further insight into and challenge traditional
views of mechanisms of lung repair after injury and pathogenesis of several lung
diseases. The goals of the conference were to summarize the current state of the
field, discuss and debate current controversies, and identify future research
directions and opportunities for both basic and translational research in cell
based therapies for lung diseases. This 10th anniversary conference was a follow
up to five previous biennial conferences held at the University of Vermont in
2005, 2007, 2009, 2011, and 2013. Each of those conferences, also sponsored by
the National Institutes of Health, American Thoracic Society, and respiratory
disease foundations, has been important in helping guide research and funding
priorities. The major conference recommendations are summarized at the end of the
report and highlight both the significant progress and major challenges in these
rapidly progressing fields.
PMID- 27509164
TI - Exploration of Unimolecular Gas-Phase Detoxication Pathways of Sarin and Soman: A
Computational Study from the Perspective of Reaction Energetics and Kinetics.
AB - A mechanistic investigation has been carried out to explore all possible gas
phase unimolecular isomerization as well as decomposition pathways of toxic
organophosphorus compounds (OPCs), namely, sarin (GB) and soman (GD), which are
better known as nerve agents. We have identified a total of 13 detoxication
pathways for sarin, where the alpha-H, beta-H, and gamma-H take part in the H
transfer process. However, for soman, due to the presence of omega-H, three
additional detoxication pathways are obtained, where the omega-H is involved in
the H-transfer process. Among all the pathways, the D3 decomposition pathway,
where the phosphorus oxoacid derivative and alkene are generated via the
formation of a six-membered ring in the transition state, is identified as the
most feasible pathway from the perspective of both activation barrier and
reaction enthalpy values. Moreover, we have studied the feasibility of the
isomerization and decomposition pathways by performing the reaction kinetics in
the temperature range of 300 K-1000 K using the one-dimensional Rice-Ramsperger
Kassel-Marcus (RRKM) master equation. From the RRKM calculation also, D3 pathway
is confirmed as the most feasible pathway for both OPCs. The rate constant values
associated with the D3 pathway within the temperature range of 600 K-700 K imply
that the degradation of the OPCs is possible within this temperature range via
the D3 pathway, which is in good agreement with the earlier reported experimental
result. It is also observed that at higher temperature range (~900 K), the
increased rate constant values of other detoxication pathways indicate that along
with D3, all other pathways become more or less equally feasible. Therefore, the
entire work provides a widespread idea about the kinetic as well as thermodynamic
feasibility of the explored detoxication pathways of the titled OPCs.
PMID- 27509165
TI - Diabetic patient adherence to pathology request completion in primary care.
AB - Objective Little research exists regarding the prevalence of patient non
adherence with completing pathology requests for chronic disease monitoring. The
aims of the present study were to determine the extent to which this exists in
diabetic patients and to identify possible reasons contributing to this
behaviour. Methods Patients diagnosed with type 2 diabetes mellitus were
recruited from three general practices with different demographics. Data were
collected by recording demographic patient information at the time of visit. In
addition, information regarding patient pathology request adherence and the
reasons provided when this was not achieved were also noted. These reasons were
compared with preconceptions by medical staff in each practice. Results General
practitioner perceptions of poor patient adherence to pathology requests were
confirmed, with rates of non-adherence up to 31% at one practice site. The
primary reasons preventing completion of pathology testing included
forgetfulness, time poorness, poor health literacy and, in some cases, language
barriers. Conclusion A high proportion of patients do not prioritise the
monitoring of their diabetes, potentially because of a lack of understanding of
the importance such management has on their health. Further research should be
conducted to determine the effect of the implementation of point-of-care testing
on patient outcomes in such areas of low non-adherence with disease management.
What is known about the topic? Little quantitative information exists regarding
the adherence rate of patients to pathology request completion. Without up-to
date pathology results, a barrier is created, preventing accurate medical
treatment of the patient's condition because the doctor cannot ascertain a full
picture of the patient's current disease state at the time of consultation. What
does this paper add? This paper quantifies the rate of non-adherence among three
diabetic patient groups at different practice sites, taking into account patient
and site demographics. It also confirms patient non-adherence to timely pathology
request completion as a prevalent issue of concern at all practice sites
recruited. In addition, it looks at reasons why this issue exists as a means of
addressing the problem in the future. What are the implications for
practitioners? This research may aid practitioners in addressing such issues at a
local level within general practice, because reasons creating barriers to
successful completion of pathology requests have been identified and potential
solutions suggested.
PMID- 27509166
TI - Polymorphism of Metastasis Suppressor Genes MKK4 and NME1 in Kashmiri Patients
with Breast Cancer.
AB - Genetic polymorphisms in metastatic suppressor genes like MKK4 and NME1 are not
well studied in breast cancer. Hence, we analyzed the relationship between MKK4
and NME1 polymorphisms and breast cancer risk in Kashmir, India. The different
genotypes of NME1 and MKK4 genes were analyzed by polymerase chain reaction and
restriction fragment length polymorphism in 130 breast cancer cases and 200 age-
and sex-matched controls. Conditional logistic regression models were used to
assess the association of various genotypes with breast cancer. In this study, we
found an inverse association between MKK4 promoter polymorphism and breast cancer
risk. As compared to TT (wild) genotype, individuals with TG (heterozygous) (OR =
0.32; 95% CI = (0.17-0.58) and GG (mutant) (OR = 0.13; CI = 0.04-0.40) genotypes
showed decreased risk of breast cancer. When participants were classified on the
basis of lymph node involvement, a strong association between NME1 heterozygous
genotype (OR = 3.82; CI = (1.54-9.44) and breast cancer was found.
PMID- 27509167
TI - Patient Blood Management in Europe: surveys on top indications for red blood cell
use and Patient Blood Management organization and activities in seven European
university hospitals.
AB - BACKGROUND AND OBJECTIVES: Patient Blood Management (PBM) in Europe is a working
group of the European Blood Alliance with the initial objective to identify the
starting position of the participating hospitals regarding PBM for benchmarking
purposes, and to derive good practices in PBM from the experience and expertise
in the participating teams with the further aim of implementing and strengthening
these practices in the participating hospitals. METHODS: We conducted two surveys
in seven university hospitals in Europe: Survey on top indications for red blood
cell use regarding usage of red blood cells during 1 week and Survey on PBM
organization and activities. RESULTS: A total of 3320 units of red blood cells
were transfused in 1 week at the seven hospitals. Overall, 61% of red cell units
were transfused to medical patients and 36% to surgical patients, although there
was much variation between hospitals. The organization and activities of PBM in
the seven hospitals were variable, but there was a common focus on optimizing the
treatment of bleeding patients, monitoring the use of blood components and
treatment of preoperative anaemia. CONCLUSION: Although the seven hospitals
provide a similar range of clinical services, there was variation in transfusion
rates between them. Further, there was variable implementation of PBM activities
and monitoring of transfusion practice. These findings provide a baseline to
develop joint action plans to further implement and strengthen PBM across a
number of hospitals in Europe.
PMID- 27509168
TI - Rheopathologic Consequence of Plasmodium vivax Rosette Formation.
AB - Malaria parasites dramatically alter the rheological properties of infected red
blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the
shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance.
This study highlights correlation between rosette formation and altered membrane
deformability of P. vivax-infected erythrocytes, where the rosette-forming
infected erythrocytes are significantly more rigid than their non-rosetting
counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding
force of 440pN) resulting in stable rosette formation even under high
physiological shear flow stress. Rosetting may contribute to the sequestration of
PvIRBC schizonts in the host microvasculature or spleen.
PMID- 27509169
TI - Differential Analysis of the Nasal Microbiome of Pig Carriers or Non-Carriers of
Staphylococcus aureus.
AB - Staphylococcus aureus is presently regarded as an emerging zoonotic agent due to
the spread of specific methicillin-resistant S. aureus (MRSA) clones in pig
farms. Studying the microbiota can be useful for the identification of bacteria
that antagonize such opportunistic veterinary and zoonotic pathogen in animal
carriers. The aim of this study was to determine whether the nasal microbiome of
pig S. aureus carriers differs from that of non-carriers. The V3-V5 region of the
16S rRNA gene was sequenced from nasal swabs of 44 S. aureus carriers and 56 non
carriers using the 454 GS FLX titanium system. Carriers and non-carriers were
selected on the basis of quantitative longitudinal data on S. aureus carriage in
600 pigs sampled at 20 Danish herds included in two previous studies in Denmark.
Raw sequences were analysed with the BION meta package and the resulting
abundance matrix was analysed using the DESeq2 package in R to identify
operational taxonomic units (OTUs) with differential abundance between S. aureus
carriers and non-carriers. Twenty OTUs were significantly associated to non
carriers, including species with known probiotic potential and antimicrobial
effect such as lactic acid-producing isolates described among Leuconostoc spp.
and some members of the Lachnospiraceae family, which is known for butyrate
production. Further 5 OTUs were significantly associated to carriage, including
known pathogenic bacteria such as Pasteurella multocida and Klebsiella spp. Our
results show that the nasal microbiome of pigs that are not colonized with S.
aureus harbours several species/taxa that are significantly less abundant in pig
carriers, suggesting that the nasal microbiota may play a role in the individual
predisposition to S. aureus nasal carriage in pigs. Further research is warranted
to isolate these bacteria and assess their possible antagonistic effect on S.
aureus for the pursuit of new strategies to control MRSA in pig farming.
PMID- 27509170
TI - Language-Appropriate Appointment Reminders: Assessing the Communication
Preferences of Women With Limited English Proficiency.
AB - INTRODUCTION: The purpose of this study was to assess the communication
preferences and the telephone, text, and e-mail usage of women with limited
English proficiency who attended an outpatient women's health clinic. METHODS:
This study surveyed a convenience sample (N = 220) of Spanish- and Arabic
speaking women in an obstetrics and gynecology clinic. The survey instrument was
designed to capture the experience of women with limited English proficiency who
received automated English-only telephone appointment reminders. We evaluated how
these women currently use short message service (SMS) technology and/or access e
mail, the costs they incur for these services, and their preferences for and
receptiveness to receiving appointment reminders through a variety of modalities
including text, e-mail, phone, or direct mail. RESULTS: More than half of women
surveyed reported either not receiving an appointment reminder or reported
difficulty understanding the reminder they did receive. Of all women surveyed,
91% preferred appointment reminders in their primary language regardless of their
ability to read, write, speak, or understand English. Significant variation in
preferences was found within and between the 2 language groups. DISCUSSION: The
data suggest that the current appointment-reminder system is both inefficient and
linguistically inappropriate for female clients with limited English proficiency.
This project offers preliminary data on the preferences of Spanish- and Arabic
speaking women. Creating language-appropriate appointment reminders in both phone
and text formats reflects an institutional commitment to the language preferences
of all women, not just those who speak the dominant language, in accordance with
accreditation guidelines defined by the Centers for Medicare and Medicaid
Services and The Joint Commission.
PMID- 27509171
TI - Brilliant Structurally Colored Films with Invariable Stop-Band and Enhanced
Mechanical Robustness Inspired by the Cobbled Road.
AB - Recently, structural colors have attracted great concentrations because the
coloration is free from chemical- or photobleaching. However, the color
saturation and mechanical robustness are generally competitive properties in the
fabrication of PCs (photonic crystals) films. Besides, the structure of PCs and
their derivatives are easy to be invaded by liquids and lead to band gap shifts
due to the change of refractive index or periodicity. To solve those problems, we
infiltrate polydimethylsiloxane (PDMS) into the intervals between regularly
arrayed hollow SiO2 nanospheres, inspired by the cobbled road prepared by
embedding stone in the bulk cement matrix. Consequently, the as-prepared PCs
films show brilliant colors, invariable stop-bands, and excellent mechanical
robustness. Moreover, the water contact angle even reached 166 degrees after a
sandpaper abrasion test. The combination of brilliant colors, invariable stop
bands, and excellent robustness is significant for potential application in paint
and external decoration of architectures.
PMID- 27509172
TI - A cohort study of cervical screening using partial HPV typing and cytology
triage.
AB - HPV testing is more sensitive than cytology for cervical screening. However, to
incorporate HPV tests into screening, risk-stratification ("triage") of HPV
positive women is needed to avoid excessive colposcopy and overtreatment. We
prospectively evaluated combinations of partial HPV typing (Onclarity, BD) and
cytology triage, and explored whether management could be simplified, based on
grouping combinations yielding similar 3-year or 18-month CIN3+ risks. We typed
~9,000 archived specimens, taken at enrollment (2007-2011) into the NCI-Kaiser
Permanente Northern California (KPNC) HPV Persistence and Progression (PaP)
cohort. Stratified sampling, with reweighting in the statistical analysis,
permitted risk estimation of HPV/cytology combinations for the 700,000+-woman
KPNC screening population. Based on 3-year CIN3+ risks, Onclarity results could
be combined into five groups (HPV16, else HPV18/45, else HPV31/33/58/52, else
HPV51/35/39/68/56/66/68, else HPV negative); cytology results fell into three
risk groups ("high-grade," ASC-US/LSIL, NILM). For the resultant 15 HPV group
cytology combinations, 3-year CIN3+ risks ranged 1,000-fold from 60.6% to 0.06%.
To guide management, we compared the risks to established "benchmark"
risk/management thresholds in this same population (e.g., LSIL predicted 3-year
CIN3+ risk of 5.8% in the screening population, providing the benchmark for
colposcopic referral). By benchmarking to 3-year risk thresholds (supplemented by
18-month estimates), the widely varying risk strata could be condensed into four
action bands (very high risk of CIN3+ mandating consideration of cone biopsy if
colposcopy did not find precancer; moderate risk justifying colposcopy; low risk
managed by intensified follow-up to permit HPV "clearance"; and very low risk
permitting routine screening.) Overall, the results support primary HPV testing,
with management of HPV-positive women using partial HPV typing and cytology.
PMID- 27509173
TI - Implementation and Operational Research: Clinical Impact of the Xpert MTB/RIF
Assay in Patients With Multidrug-Resistant Tuberculosis.
AB - BACKGROUND: The Xpert MTB/RIF assay has been widely implemented in South Africa
for rapid tuberculosis (TB) screening. However, its usefulness in management and
improving treatment outcomes in patients with multidrug-resistant TB (MDR-TB)
remains undefined. The aim of this study was to evaluate the clinical impact of
introduction of the Xpert MTB/RIF assay in patients with MDR-TB. METHODS: We
enrolled 921 patients with MDR-TB, who presented to a specialist drug-resistant
TB facility in KwaZulu-Natal, South Africa, pre- and post-rollout and
implementation of the Xpert MTB/RIF assay. Clinical, laboratory, chest
radiograph, and follow-up data from 108 patients with MDR-TB, post-introduction
of the Xpert MTB/RIF assay (Xpert group) in November 2010, were analyzed and
compared with data from 813 MDR-TB patients from the pre-MTB/RIF assay period
(Conventional group), July 2008-2010. Primary impact measure was "treatment
success" (World Health Organization definition) at 24 months. Secondary outcomes
were time to treatment initiation and disease morbidity. RESULTS: There were no
significant differences in treatment success rates between the pre-Xpert MTB/RIF
and post-Xpert MTB/RIF groups (54% versus 56.5%, P = 0.681). Median time to
treatment initiation was 20 days (interquartile range, 13-31) in the Xpert group
versus 92 days (interquartile range, 69-120) in the Conventional group (P <
0.001). CONCLUSIONS: Although use of Xpert MTB/RIF assay significantly reduces
the time to initiation of MDR-TB treatment, it had no significant impact on
treatment outcomes of patients with MDR-TB. Studies on the impact of the Xpert
MTB/RIF assay usage on transmission of MDR-TB are required.
PMID- 27509174
TI - Circulating resistin levels and obesity-related cancer risk: A meta-analysis.
AB - Resistin levels have been reported to be abnormal in obesity-related cancer
patients with epidemiological studies yielding inconsistent results. Therefore, a
meta-analysis was performed to assess the association between blood resistin
levels and obesity-related cancer risk. A total of 13 studies were included for
pooling ORs analysis. High resistin levels were found in cancer patients (OR=
1.20, 95% CI= 1.10-1.30). After excluding one study primarily contributing to
between-study heterogeneity, the association between resistin levels and cancer
risk was still significant (OR=1.18, 95% CI = 1.09-1.28). Stratification analysis
found resistin levels were not associated with cancer risk in prospective
studies. Meta-regression analysis identified factors such as geographic area,
detection assay, or study design as confounders to between-study variance. The
result of 18 studies of pooling measures on SMD analysis was that high resistin
levels were associated with increased cancer risk (SMD = 0.94, 95% CI = 0.63
1.25), but not in the pooling SMD analysis of prospective studies. Except for the
studies identified as major contributors to heterogeneity by Galbraith plot,
resistin levels were still higher in cancer patients (SMD = 0.75, 95% CI = 0.63
0.87) in retrospective studies. Meta-regression analysis found factors, such as
geographic area, BMI-match, size, and quality score, could account for 66.7%
between-study variance in pooling SMD analysis of retrospective studies.
Publication bias was not found in pooling ORs analysis. Our findings indicated
high resistin levels were associated with increased obesity-related cancer risk.
However, it may not be a predictor.
PMID- 27509175
TI - A new predictive model combined of tumor size, lymph nodes count and
lymphovascular invasion for survival prognosis in patients with lymph node
negative gastric cancer.
AB - BACKGROUND: Various factors may affect the clinical prognosis of lymph node
negative gastric cancer (GC) patients. This study aimed to provide evaluable
prognostic information of combination of tumor size (Ts), lymph nodes count (LNs)
and lymphovascular invasion (LVI) in lymph node-negative GC patients. METHODS: A
total of 1,019 node-negative GC patients were enrolled in this retrospective
study from 2000 to 2010. The cutoff points of Ts and LNs were determined using X
tile and patients were randomly categorized into training and validation sets by
the sample size ratio 1:1. The clinicopathologic characteristics were analyzed
and survival prognostic factors were identified, whereas the survival prediction
accuracy was also compared by C-index during the different independent prognostic
factors. RESULTS: The cutoff points for Ts were 3cm and 5cm, while 14 was the
cutoff point for LNs. Age, T stage, Ts, LNs and LVI were identified as
independent prognostic factors in node-negative GC patients, and a new prognostic
predictive model, TsNL staging system which was composed of Ts, LNs and LVI, was
proposed in this study. Compared with T staging system, significant improvement
of predictive accuracy for TsNL system was found. Furthermore, nomogram based on
TsNL was more accurate in prognostic prediction than that based on Ts, LNs and
LVI, separately. CONCLUSIONS: Age, T stage, Ts, LNs and LVI were independent
prognostic factors in lymph node-negative GC patients. The TsNL staging system,
composed of Ts, LNs and LVI, which was closely associated with clinicopathologic
features, may improve the prognostic prediction accuracy in node-negative GC
patients.
PMID- 27509177
TI - Smoking, second-hand smoke exposure and smoking cessation in relation to
leukocyte telomere length and mortality.
AB - OBJECTIVES: To investigate the link between smoking exposure, telomere length and
mortality, with emphasis on second-hand smoke (SHS) exposure and the duration of
smoking cessation. RESULTS: A total of 1,018 participants died during follow-up
(mean: 10.3 years). A 50 base-pair decrease in LTL was shown among cotinine
confirmed current versus never smokers. The 90th quantile of LTL decreased with
increasing cotinine among never smokers, indicating a role of SHS. Longer
telomeres with smoking cessation were indicated but limited to a 3-16 year period
of abstaining smoking. When assessing mortality, we observed a lower risk of all
cause death for the second quintile compared to the first among never smokers
(HR: 0.67, 95% CI: 0.52-0.87), and a higher risk was found among current smokers
(HR: 1.89, 1.19-2.92). MATERIALS AND METHODS: We studied 6,456 nationally
representative U.S. respondents with mortality follow-up through to 31 December
2011. Smoking status was assessed by interviews and cotinine levels. Relative
leukocyte telomere length (LTL) was quantified by polymerase chain reaction
(PCR). Multivariable linear regression was performed to examine LTL by smoking
exposure, adjusted for age, sex, race/ethnicity, socioeconomic status, education,
body mass index, alcohol consumption, and physical activity. We further estimated
the association of LTL with cotinine levels using quantile regression, and with
smoking cessation dynamics. Cox regression was used to estimate mortality by
smoking status and LTL. CONCLUSION: Our findings indicated a complex association
between smoking, telomere length, and mortality. LTL alterations with SHS and
smoking cessation warrant further investigation for translation to public health
measures.
PMID- 27509178
TI - Cancer diagnostics: The journey from histomorphology to molecular profiling.
AB - Although histomorphology has made significant advances into the understanding of
cancer etiology, classification and pathogenesis, it is sometimes complicated by
morphologic ambiguities, and other shortcomings that necessitate the development
of ancillary tests to complement its diagnostic value. A new approach to cancer
patient management consists of targeting specific molecules or gene mutations in
the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic
profiling methods are increasingly being developed to identify tumor targeted
molecular profile that is the basis of targeted therapy. Novel targeted therapy
has revolutionized the treatment of gastrointestinal stromal tumor, renal cell
carcinoma and other cancers that were previously difficult to treat with standard
chemotherapy. In this review, we discuss the role of histomorphology in cancer
diagnosis and management and the rising role of molecular profiling in targeted
therapy. Molecular profiling in certain diagnostic and therapeutic difficulties
may provide a practical and useful complement to histomorphology and opens new
avenues for targeted therapy and alternative methods of cancer patient
management.
PMID- 27509179
TI - Heritability of Caffeine Metabolism: Environmental Effects Masking Genetic
Effects on CYP1A2 Activity but Not on NAT2.
AB - Heritability of caffeine pharmacokinetics and cytochrome P450 1A2 (CYP1A2)
activity is controversial. Here, we analyzed the pharmacokinetics of caffeine, an
in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2)
activity, in monozygotic (MZ) and dizygotic (DZ) twins. In the entire group,
common and unique environmental effects explained most variation in caffeine area
under the curve (AUC). Apparently, smoking and hormonal contraceptives masked the
genetic effects on CYP1A2 activity. However, when excluding smokers and users of
hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects
and, even in the entire group, 8% of caffeine AUC variation could be explained by
a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the
variations (99%) of NAT2 activity were explained by genetic effects. This study
illustrates two very different situations in pharmacogenetics from an almost
exclusively genetic determination of NAT2 activity with no environmental
modulation to only moderate genetic effects on CYP1A2 activity with strong
environmental modulation.
PMID- 27509180
TI - Biocompatibility, resorption and biofunctionality of a new synthetic
biodegradable membrane for guided bone regeneration.
AB - Membranes for guided bone regeneration (GBR) were prepared from the synthetic
biodegradable polymer poly-D,L-lactic/glycolic acid (PLGA). This GBR membrane has
a bi-layered structure with a dense film to prevent gingival fibroblast ingrowth
and ensure mechanical function, and a micro-fibrous layer to support colonization
by osteogenic cells and promote bone regeneration. Hydrolysis and biodegradation
were both studied in vitro through soaking in phosphate buffered saline (PBS) and
in vivo by implantation in the subcutis of rats for 4, 8, 16, 26, 48 and 52
weeks. Histology revealed an excellent colonization of the micro-fibrous layer by
cells with a minimal inflammatory reaction during resorption. GBR using the
synthetic PLGA membrane was evaluated on critical-size calvaria defects in rats
for 4 and 8 weeks. Radiographs, micro-computed tomography and histology showed
bone regeneration with the PLGA membrane, while the defects covered with a
collagen membrane showed a limited amount of mineralized bone, similar to that of
the defect left empty. The biofunctionality of the PLGA membranes was also
compared to collagen membranes in mandible defects in rabbits, associated or not
with beta-tricalcium phosphate granules. This study revealed that the bi-layered
synthetic membrane made of PLGA was safer, more biocompatible, and had a greater
controlled resorption rate and bone regeneration capacity than collagen
membranes. This new PLGA membrane could be used in pre-implantology and peri
odontology surgery.
PMID- 27509181
TI - Association between Single Nucleotide Polymorphisms in Gamma-Aminobutyric Acid B
Receptor, Insulin Receptor Substrate-1, and Hypocretin Neuropeptide Precursor
Genes and Susceptibility to Obstructive Sleep Apnea Hypopnea Syndrome in a
Chinese Han Population.
AB - OBJECTIVE: To investigate genotype-phenotype changes between rs29230 in gamma
aminobutyric acid B receptor (GABBR1), rs1801278 in insulin receptor substrate-1
(IRS-1), and rs9902709 in hypocretin neuropeptide precursor (HCRT) and
obstructive sleep apnea hypopnea syndrome (OSAHS) in Chinese Han individuals.
MATERIALS AND METHODS: A total of 130 patients with OSAHS and 136 age- and gender
matched healthy controls were enrolled in this study. A brief description of DNA
extraction and genotyping is given. Multivariate unconditional logistic
regression analysis adjusted for gender and age was used to estimate the
associations of single nucleotide polymorphisms (SNPs) rs29230 (GABBR1),
rs1801278 (IRS-1), and rs9902709 (HCRT) with OSAHS risk. Subgroup analysis was
performed to evaluate differences in these SNPs among subgroups according to
gender, body mass index (BMI), and severity of disease. RESULTS: Genotype and
allele frequencies of rs29230 were significantly different between cases and
controls (p = 0.0205 and p = 0.0191, respectively; odds ratio = 0.493, 95%
confidence interval = 0.271-0.896), especially for male patients (p = 0.0259 and
p = 0.0202, respectively). Subgroup analysis according to BMI also revealed a
significant allele difference for rs29230 between cases and controls in the
overweight subgroup (p = 0.0333). Furthermore, allele and genotype frequencies of
rs1801278 showed significant differences between cases and controls (p = 0.0488
and p = 0.0471, respectively). However, no association was observed between
rs9902709 and OSAHS risk (p = 0.2762), and no differences were identified in
other subgroups. CONCLUSION: In this study, there was an association between
variants of rs29230 and rs1801278 and OSAHS risk in the Chinese Han population
but not for rs9902709.
PMID- 27509182
TI - Facility-Level Factors Influencing Retention of Patients in HIV Care in East
Africa.
AB - Losses to follow-up (LTFU) remain an important programmatic challenge. While
numerous patient-level factors have been associated with LTFU, less is known
about facility-level factors. Data from the East African International
epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium was used to
identify facility-level factors associated with LTFU in Kenya, Tanzania and
Uganda. Patients were defined as LTFU if they had no visit within 12 months of
the study endpoint for pre-ART patients or 6 months for patients on ART.
Adjusting for patient factors, shared frailty proportional hazard models were
used to identify the facility-level factors associated with LTFU for the pre- and
post-ART periods. Data from 77,362 patients and 29 facilities were analyzed.
Median age at enrolment was 36.0 years (Interquartile Range: 30.1, 43.1), 63.9%
were women and 58.3% initiated ART. Rates (95% Confidence Interval) of LTFU were
25.1 (24.7-25.6) and 16.7 (16.3-17.2) per 100 person-years in the pre-ART and
post-ART periods, respectively. Facility-level factors associated with increased
LTFU included secondary-level care, HIV RNA PCR turnaround time >14 days, and no
onsite availability of CD4 testing. Increased LTFU was also observed when no
nutritional supplements were provided (pre-ART only), when TB patients were
treated within the HIV program (pre-ART only), and when the facility was open <=4
mornings per week (ART only). Our findings suggest that facility-based strategies
such as point of care laboratory testing and separate clinic spaces for TB
patients may improve retention.
PMID- 27509183
TI - Older Rural- and Urban-Dwelling Appalachian Adults With Mild Cognitive
Impairment.
AB - PURPOSE: Mild cognitive impairment (MCI) is a well-recognized risk state for
Alzheimer's disease and other dementias. MCI is rapidly increasing among older
adults in general and has not yet been examined in older adults within the
Appalachian region. Our objective was to compare MCI symptom severity among older
rural and urban Appalachian adults with MCI at an initial neuropsychological
testing visit. METHODS: A cross-sectional, descriptive study of older Appalachian
adults with MCI was conducted using data from the National Alzheimer's
Coordinating Center Uniform Data Set. Symptom severity was conceptualized as
neuropsychological composite scores across 4 cognitive domains and Clinical
Dementia Rating-Sum of Boxes (CDR-SOB) score. For group comparisons, MANCOVA was
used for cognitive domains and ANCOVA for CDR-SOB. RESULTS: The sample (N = 289)
was about half male (54.3%), predominantly white (91.7%), and living with others
(83.5%), with a mean (+/-SD) 74.6 +/- 6.2 years of age and 15.4 +/- 3.0 years of
education. Rural and urban groups differed significantly in years since onset of
cognitive symptoms (2.98 +/- 1.91 in rural and 3.89 +/- 2.70 in urban adults,
t[260] = -2.23, P = .03), but they did not differ across sociodemographic
features or comorbid conditions. Rural and urban participants were similar across
the 4 cognitive domains and CDR-SOB (P >= .05). DISCUSSION: No differences were
found between rural and urban Appalachian residents on MCI symptom severity.
However, urban residents reported a longer time lapse from symptom identification
to diagnosis than their rural counterparts. Future studies using more
representative population samples of Appalachian and non-Appalachian adults will
provide an important next step to identifying disparate cognitive health outcomes
in this traditionally underserved region.
PMID- 27509184
TI - Identification of resveratrol analogs as potent anti-dengue agents using a cell
based assay.
AB - Dengue virus (DENV) causes a variety of difficult-to-treat diseases that threaten
almost half of the world's population. Currently, no effective vaccine or
antiviral therapy is available. We have examined a series of synthetic
resveratrol analogs to identify potential anti-DENV agents. Here, we demonstrate
that two resveratrol analogs, PNR-4-44 and PNR-5-02, possess potent anti-DENV
activity with EC50 values in the low nanomolar range. These two resveratrol
analogs were shown to mainly target viral RNA translation and viral replication,
but PNR-5-02 is also likely to target cellular factors inside host cells.
Although the precise molecular mechanism(s) mediating anti-DENV activities have
not been elucidated, further structure-guided design might lead to the
development of newer improved resveratrol derivatives that might have therapeutic
value. J. Med. Virol. 89:397-407, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27509185
TI - From Metaphors to Formalism: A Heuristic Approach to Holistic Assessments of
Ecosystem Health.
AB - Environmental policies employ metaphoric objectives such as ecosystem health,
resilience and sustainable provision of ecosystem services, which influence
corresponding sustainability assessments by means of normative settings such as
assumptions on system description, indicator selection, aggregation of
information and target setting. A heuristic approach is developed for
sustainability assessments to avoid ambiguity and applications to the EU Marine
Strategy Framework Directive (MSFD) and OSPAR assessments are presented. For
MSFD, nineteen different assessment procedures have been proposed, but at present
no agreed assessment procedure is available. The heuristic assessment framework
is a functional-holistic approach comprising an ex-ante/ex-post assessment
framework with specifically defined normative and systemic dimensions (EAEPNS).
The outer normative dimension defines the ex-ante/ex-post framework, of which the
latter branch delivers one measure of ecosystem health based on indicators and
the former allows to account for the multi-dimensional nature of sustainability
(social, economic, ecological) in terms of modeling approaches. For MSFD, the ex
ante/ex-post framework replaces the current distinction between assessments based
on pressure and state descriptors. The ex-ante and the ex-post branch each
comprise an inner normative and a systemic dimension. The inner normative
dimension in the ex-post branch considers additive utility models and likelihood
functions to standardize variables normalized with Bayesian modeling. Likelihood
functions allow precautionary target setting. The ex-post systemic dimension
considers a posteriori indicator selection by means of analysis of indicator
space to avoid redundant indicator information as opposed to a priori indicator
selection in deconstructive-structural approaches. Indicator information is
expressed in terms of ecosystem variability by means of multivariate analysis
procedures. The application to the OSPAR assessment for the southern North Sea
showed, that with the selected 36 indicators 48% of ecosystem variability could
be explained. Tools for the ex-ante branch are risk and ecosystem models with the
capability to analyze trade-offs, generating model output for each of the
pressure chains to allow for a phasing-out of human pressures. The Bayesian
measure of ecosystem health is sensitive to trends in environmental features, but
robust to ecosystem variability in line with state space models. The combination
of the ex-ante and ex-post branch is essential to evaluate ecosystem resilience
and to adopt adaptive management. Based on requirements of the heuristic
approach, three possible developments of this concept can be envisioned, i.e. a
governance driven approach built upon participatory processes, a science driven
functional-holistic approach requiring extensive monitoring to analyze complete
ecosystem variability, and an approach with emphasis on ex-ante modeling and ex
post assessment of well-studied subsystems.
PMID- 27509186
TI - Structural Insights into the PorK and PorN Components of the Porphyromonas
gingivalis Type IX Secretion System.
AB - The type IX secretion system (T9SS) has been recently discovered and is specific
to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for
periodontitis, utilizes the T9SS to transport many proteins including the
gingipain virulence factors across the outer membrane and attach them to the cell
surface via a sortase-like mechanism. At least 11 proteins have been identified
as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the
precise roles of most of these proteins have not been elucidated and the
structural organization of these components is unknown. In this study, we
purified PorK and PorN complexes from P. gingivalis and using electron microscopy
we have shown that PorN and the PorK lipoprotein interact to form a 50 nm
diameter ring-shaped structure containing approximately 32-36 subunits of each
protein. The formation of these rings was dependent on both PorK and PorN, but
was independent of PorL, PorM and PorP. PorL and PorM were found to form a
separate stable complex. PorK and PorN were protected from proteinase K cleavage
when present in undisrupted cells, but were rapidly degraded when the cells were
lysed, which together with bioinformatic analyses suggests that these proteins
are exposed in the periplasm and anchored to the outer membrane via the PorK
lipid. Chemical cross-linking and mass spectrometry analyses confirmed the
interaction between PorK and PorN and further revealed that they interact with
the PG0189 outer membrane protein. Furthermore, we established that PorN was
required for the stable expression of PorK, PorL and PorM. Collectively, these
results suggest that the ring-shaped PorK/N complex may form part of the
secretion channel of the T9SS. This is the first report showing the structural
organization of any T9SS component.
PMID- 27509187
TI - The Effect of High Dose Cholecalciferol on Arterial Stiffness and Peripheral and
Central Blood Pressure in Healthy Humans: A Randomized Controlled Trial.
AB - BACKGROUND: Low levels of serum 25-hydroxy vitamin D are associated with
increased arterial stiffness and hypertension. Supplementation with vitamin D
precursors has been proposed as a treatment option for these conditions. We
examined the effect of oral cholecalciferol on arterial stiffness and blood
pressure in healthy normotensive adults. METHODS: 40 healthy adults were
randomised in this double-blinded study to either oral cholecalciferol 3000
IU/day or matching placebo and were followed for 16 weeks to examine any effects
on pulse wave velocity (PWV), augmentation index (AIx), peripheral and central
blood pressure and 24-hour ambulatory blood pressure. RESULTS: 22 subjects in the
cholecalciferol arm and 18 subjects in the placebo arm completed the 16 weeks of
follow-up. There was no difference in changes in PWV, AIx corrected for heart
rate or central or peripheral blood pressure between the two groups. There was no
correlation between serum 25-hydroxy vitamin D and any of these parameters.
CONCLUSIONS: Oral cholecalciferol 3000 IU/day does not affect arterial stiffness
or blood pressure after 16 weeks of treatment in healthy normotensive adults.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00952562.
PMID- 27509188
TI - A comparison of hemodynamic metrics and intraluminal thrombus burden in a common
iliac artery aneurysm.
AB - Aneurysms of the common iliac artery (CIAA) are typically found in association
with an abdominal aortic aneurysm (AAA). Isolated CIAAs, in the absence of an
AAA, are uncommon. Similar to AAAs, CIAA may develop intraluminal thrombus (ILT).
As isolated CIAAs have a contralateral common iliac artery for comparison, they
provide an opportunity to study the hemodynamic mechanisms behind ILT formation.
In this study, we compared a large isolated CIAA and the contralateral iliac
artery using computational fluid dynamics to determine if hemodynamic metrics
correlate with the location of ILT. We performed a comprehensive computational
fluid dynamics study and investigated the residence time of platelets and
monocytes, velocity fields, time-averaged wall shear stress, oscillatory shear
index, and endothelial cell activation potential. We then correlated these data
to ILT burden determined with computed tomography. We found that high cell
residence times, low time-averaged wall shear stress, high oscillatory shear
index, and high endothelial cell activation potential all correlate with regions
of ILT development. Our results show agreement with previous hypotheses of
thrombus formation in AAA and provide insights into the computational
hemodynamics of iliac artery aneurysms.
PMID- 27509189
TI - Prevalence and Imaging Characteristics of Nonmyelopathic and Myelopathic
Spondylotic Cervical Cord Compression.
AB - STUDY DESIGN: Cross-sectional population-based observational study. OBJECTIVE: To
estimate the prevalence of nonmyelopathic spondylotic cervical cord compression
(NMSCCC) and cervical spondylotic myelopathy (CSM) in a population older than 40
years and to evaluate the magnetic resonance imaging (MRI) characteristics of
these conditions. SUMMARY OF BACKGROUND DATA: The prevalence of neither NMSCCC
nor CSM is known and there exists no commonly accepted quantitative MRI
definition of cervical cord compression. METHODS: A group of 183 randomly
recruited volunteers, 93 women, median age 66 years, range 40-80 years, underwent
MRI examination of the cervical spine and spinal cord on a 1.5 T device using
conventional sequences from disc levels C2/C3 to C6/C7. The imaging criterion for
cervical cord compression was defined as a change in spinal cord contour at the
level of an intervertebral disc on axial or sagittal MRI scan. RESULTS: MRI signs
of cervical cord compression were found in 108 individuals (59.0%; 95% CI: 51.5%
66.2%); their numbers increased with age from 31.6% in the fifth decade to 66.8%
in the eighth. Clinical signs of symptomatic CSM were found in two cases (1.1%),
and 75 cases (41.0%) were without compression. An anteroposterior cervical canal
diameter at the level of intervertebral disc (CDdisc) of less than 9.9 mm was
associated with the highest probability of NMSCCC-odds ratio (OR) = 32.5,
followed by a compression ratio of <=0.5: OR = 11.1. CONCLUSION: The prevalence
of NMSCCC in a population older than 40 years is higher than previously reported
and increases with age. CDdisc and compression ratio had the highest capacity to
discriminate between subjects with and without asymptomatic compression, and
their cut-off values could be used to objectify criteria for cervical cord
compression. LEVEL OF EVIDENCE: 2.
PMID- 27509190
TI - Instrumentation Failure After Posterior Vertebral Column Resection in Adult
Spinal Deformity.
AB - STUDY DESIGN: Retrospective study of instrumentation failure after posterior
vertebral column resection (pVCR) in adult spinal deformity (ASD) patients.
OBJECTIVE: The morbidity and related risk factors of the instrumentation failure.
SUMMARY OF BACKGROUND DATA: Instrumentation failure is another common
complication after pVCR. But no report about it has been published before. The
safety of titanium mesh cages (TMCs) for this failure is still unknown so far.
METHODS: A total of 35 consecutive ASD patients (18 females and 17 males), who
underwent pVCR between May 2005 and December 2014 in our hospital, were
retrospectively reviewed. The mean age and follow-up period were 37.8 +/- 12.8
years and 45.5 +/- 27.3 months. Proportion was used to describe the morbidity of
instrumentation failure. Potential risk factors were compared between patients
with and without instrumentation failures by using Student t test or chi tests
(Fisher exact tests). Risk factors related to TMCs were analyzed in TMC group.
RESULTS: There were 70 vertebra resected in total, with the mean of 10.3 segments
instrumented. The mean correction rates of main curve (n = 25) and segmental
kyphosis (n = 35) were 68.8% and 67.9%, respectively. Five patients (14.3%)
suffered rod breakage. The failure was noted an average of 6.8 months after
surgery. The risk factors included BMI (>27, P = 0.026), comorbidity
(Achondroplasia, P = 0.047), and anterior column defect (ACD>20 mm, P = 0.045).
TMC subsidence of >=5 mm was the risk factor related to TMC in TMC group (P =
0.041). CONCLUSION: It is safe to reconstruct with a TMC after pVCR in ASD, but
the height should be as low as possible to reduce ACD. For those patients with
risk factors, autologous bone graft and a satellite rod should be considered. If
TMC subsidence >=5 mm, a frequent follow-up should be performed. LEVEL OF
EVIDENCE: 4.
PMID- 27509191
TI - The Facet Orientation of the Subaxial Cervical Spine and the Implications for
Cervical Movements and Clinical Conditions.
AB - STUDY DESIGN: Computed tomography study. OBJECTIVE: To obtain detailed
information on the facet orientation in the subaxial cervical spine and explore
the correlation to the cervical movements and relevant clinical conditions.
SUMMARY OF BACKGROUND DATA: Although facet orientation was well studied in the
lumbar spine, the literatures on the cervical facet orientation were limited and
the descriptions were nonspecific. METHODS: The computed tomography scans of 100
individuals were reconstructed. For each level from C2/C3 to C6/C7, the
horizontal plane, the mid-sagittal plane, the coronal plane, and the two facet
planes were established. The normal vectors of the five planes were used for the
calculation of the facet orientation and the facet tropism. RESULTS: The angle of
the facet plane with respect to the horizontal plane at the C6/7 level was the
largest (left side: 64.34 degrees +/- 6.60 degrees , right side: 63.37 degrees
+/- 6.81 degrees , P >0.05). The angle of the facet plane with respect to the
coronal plane decreased from C2/C3 level to C6/C7 level. Regarding the angle of
the facet plane with respect to the sagittal plane, for the paired facet joints,
three types were found: posteromedially oriented, posterolaterally oriented, and
ipsilaterally oriented. All (100%) of the facet joints at the C2/C3 level and 65%
at the C3/C4 level were posteromedially oriented. In the lower levels of the
cervical spine, the posteromedially oriented facet joints were less common. The
facet tropism was common phenomenon in the subaxial cervical spine. CONCLUSION:
This study provided detailed information on the facet orientation in the subaxial
cervical spine. The cervical facet orientation correlated well with the spinal
movements and related clinical conditions. LEVEL OF EVIDENCE: 3.
PMID- 27509192
TI - The Influence of Pre- and Postoperative Fear Avoidance Beliefs on Postoperative
Pain and Disability in Patients With Lumbar Spinal Stenosis: Analysis of the
Lumbar Spinal Outcome Study (LSOS) Data.
AB - STUDY DESIGN: Prospective multicenter cohort study. OBJECTIVE: To evaluate the
effect of pre- and postoperatively assessed fear avoidance beliefs (FAB) on pain
and disability in patients with degenerative lumbar spinal stenosis (LSS) after
decompression surgery. SUMMARY OF BACKGROUND DATA: To the present, the influence
of pre- and postoperative FAB on the prognosis after surgery for LLS is still
unclear. METHODS: Patients of the Swiss Lumbar Stenosis Outcome Study (LSOS) with
confirmed LSS undergoing first-time decompression without fusion were enrolled in
this study. The main outcome of this study was minimal clinically important
difference (MCID) in spinal stenosis measure symptoms (pain) and function
(disability) after 12 months. To analyze the influence of pre- and
postoperatively assessed FAB on pain and disability we built simple and multiple
logistic regression models. RESULTS: In this analysis of 234 patients undergoing
decompression surgery for symptomatic degenerative LSS we found baseline FAB
measured by the FAB physical activity subscale (FABQ-P) not to be associated with
pain (OR 0.95; 95% CI: 0.55-1.67) and disability (OR 1.11; 95% CI: 0.64-1.92) at
12 months' follow-up. In the final multiple logistic regression models patients
with high FABQ-P at 6 months (OR 0.46; 95% CI: 0.24-0.91) and high persistent
FABQ-P at baseline and 6 months (OR 0.34, 95% CI: 0.16-0.73) were less likely to
report a MCID for spinal stenosis measure symptoms at 12 months. Our analysis
found a similar trend for disability; however, the results were not statistically
significant. CONCLUSION: In elderly patients undergoing decompression surgery for
symptomatic degenerative LSS preoperative fear avoidance beliefs were not a
prognostic indicator for the outcome. Patients with FAB at 6 months and
persistent FAB were less likely to experience clinically relevant improvement in
pain at 12 months. Studies should address the importance of persistent
postoperative FAB. LEVEL OF EVIDENCE: 3.
PMID- 27509193
TI - Soft Tissue and Bone Defect Management in Total Sacrectomy for Primary Sacral
Tumors: A Systematic Review With Expert Recommendations.
AB - STUDY DESIGN: Systematic review and expert consensus. OBJECTIVE: To address the
following two questions: (A) Is there a difference in outcomes after spino-pelvic
reconstruction of total sacrectomy defects compared with no reconstruction? (B)
What constitutes best surgical technique for soft tissue and bony reconstruction
after total sacrectomy? SUMMARY OF BACKGROUND DATA: The management of the soft
tissue and bony defect after total sacrectomy for primary sacral tumors remains a
challenge due to the complex anatomical relationships and biomechanical
requirements. The scarcity of evidence-based literature in this specialized field
makes it difficult for the treating surgeon to make an informed choice. METHODS:
A systematic literature review was performed (1950-2015), followed by a meeting
of an international expert panel. Medline, Embase, and CINAHL databases and
Cochrane Libraries were searched. Using the GRADE guidelines, the panel of
experts formulated recommendations based on the available evidence. RESULTS:
Three hundred fifty-three studies were identified. Of these, 17 studies were
included and were case series. Seven were evaluated as high quality of evidence
and nine were of low quality. There were a total of 116 participants. Three
studies included patients (n = 24) with no spino-pelvic reconstruction. One study
included patients (n = 3) with vascularized bone reconstruction. Twelve studies
included patients (n = 80) with no soft tissue reconstruction, three studies
described patients with a local flap (n = 20), and four studies with patients
having regional flap reconstruction (n = 16). Patients with or without spino
pelvic reconstruction had similar outcomes with regards to walking; however, most
patients in the nonreconstructed group had some ilio-lumbar ligamentous stability
preserved. The wound dehiscence and return to theater rates were higher in
patients with no soft tissue reconstruction. CONCLUSION: We recommend spino
pelvic reconstruction be undertaken with soft tissue reconstruction after total
sacrectomy. LEVEL OF EVIDENCE: N/A.
PMID- 27509194
TI - Changing the Adverse Event Profile in Metastatic Spine Surgery: An Evidence-Based
Approach to Target Wound Complications and Instrumentation Failure.
AB - STUDY DESIGN: Systematic review. OBJECTIVE: To identify risk factors and
preventive methods for wound complications and instrumentation failure after
metastatic spine surgery. SUMMARY OF BACKGROUND DATA: We focused on two
postoperative complications of metastatic spine tumor surgery: wound
complications and instrumentation failure and preventive measures. METHODS: We
performed a systematic review of the literature from 1980 to 2015. The articles
were analyzed for the presence of documented infection and/or wound complications
and instrumentation failure. RESULTS: Forty articles met our inclusion criteria
for wound complications and prevention. There is very low level of evidence that
preoperative radiation, preoperative neurological deficit, revision procedures,
and posterior approaches can contribute to wound complications (infections, wound
dehiscence). There is very low level of evidence that plastic surgery soft tissue
reconstruction, intrawound vancomycin powder, and percutaneous pedicle screws may
prevent postoperative wound complications. Fourteen articles met our inclusion
criteria for instrumentation failure. There is very low level of evidence that
constructs greater than six levels, positive sagittal balance, preoperative
radiation, and history of chest wall resection can contribute to implant
failures. CONCLUSION: * For patients undergoing revision metastatic spine tumor
surgery, plastic surgery should perform the soft tissue reconstruction (strong
recommendation/very low quality of evidence).* For patients undergoing metastatic
spine tumor surgery, plastic surgery may perform immediate soft tissue
reconstruction (weak recommendation/very low quality of evidence).* For patients
undergoing metastatic spine tumor surgery, intrawound vancomycin can be applied
to decrease the risk of postoperative wound infections (weak recommendation/very
low quality of evidence).* For patients undergoing metastatic spine tumor
surgery, percutaneous pedicle screws can be placed to decrease the risk of
postoperative wound complications (weak recommendation/very low quality of
evidence).* Instrumentation failure risk factors include constructs greater than
six levels, positive sagittal balance, preoperative radiation, and history of
chest wall resections (weak recommendation/very low quality of evidence). LEVEL
OF EVIDENCE: N/A.
PMID- 27509195
TI - Safety and Local Control of Radiation Therapy for Chordoma of the Spine and
Sacrum: A Systematic Review.
AB - STUDY DESIGN: Systematic literature review. OBJECTIVE: To assess the toxicity,
common radiation doses, and local control (LC) rates of radiation therapy for
chordoma of the spine and sacrum and identify the difference in LC and toxicity
between adjuvant, salvage, and primary therapy using radiation. SUMMARY OF
BACKGROUND DATA: Chordoma of the spine is typically a low-grade malignant tumor
thought to be relatively radioresistant with a high rate of local recurrence and
the potential for metastases. Improved results of modern radiation therapy in the
treatment of chordoma support exploration of its role in the management of
primary/de novo chordoma or recurrent chordoma. METHODS: We conducted a
systematic literature review using PubMed and Embase databases to assess
information available regarding the toxicity, LC rates, and overall survival (OS)
rates for adjuvant, salvage, and primary radiation therapy for spinal and sacral
chordoma. RESULTS: A total of 40 articles were reviewed. Evidence quality was low
or very low. The highest rates of LC and OS were with early adjuvant RT for
primary/de novo disease. Salvage RT for recurrent disease has very small cohorts
and thus strong conclusions were not able be made. CONCLUSION: The use of pre-
and/or post-operative photon image-guided radiotherapy (IGRT), proton or carbon
ion therapy should be considered for patients undergoing surgery for the
treatment of primary and recurrent chordomas in the mobile spine and sacrum,
since these RT modalities may improve local control. Preoperative evaluation by
the surgeon and radiation oncologist should be used to formulate a cohesive
treatment plan.The use of photon IGRT or carbon ion therapy as the primary
treatment of chordoma, when currently in its developmental stage, shows promise
and requires clear delineation of toxicity profile and long-term local control.
LEVEL OF EVIDENCE: 2.
PMID- 27509197
TI - Oscillations of Bubble Shape Cause Anomalous Surfactant Diffusion: Experiments,
Theory, and Simulations.
AB - We investigate, both theoretically and experimentally, the role played by the
oscillations of the cell membrane on the capture rate of substances freely
diffusing around the cell. To obtain quantitative results, we propose and build
up a reproducible and tunable biomimetic experimental model system to simulate
the phenomenon of an oscillation-enhanced (or depressed) capture rate
(chemoreception) of a diffusant. The main advantage compared to real biological
systems is that the different oscillation parameters (type of deformation,
frequencies, and amplitudes) can be finely tuned. The model system that we use is
an anchored gas drop submitted to a diffusive flow of charged surfactants. When
the surfactant meets the surface of the bubble, it is reversibly adsorbed. Bubble
oscillations of the order of a few nanometers are selectively excited, and
surfactant transport is accurately measured. The surfactant concentration past
the oscillating bubbles was detected by conductivity measurements. The results
highlight the role of surface oscillations on the diffusant capture rate.
Particularly unexpected is the onset of intense overshoots during the adsorption
process. The phenomenon is particularly relevant when the bubbles are exposed to
intense forced oscillations near resonance.
PMID- 27509198
TI - Pyridyl-alanine as a Hydrophilic, Aromatic Element in Peptide Structural
Optimization.
AB - Glucagon (Gcg) 1 serves a seminal physiological role in buffering against
hypoglycemia, but its poor biophysical properties severely complicate its
medicinal use. We report a series of novel glucagon analogues of enhanced aqueous
solubility and stability at neutral pH, anchored by Gcg[Aib16]. Incorporation of
3- and 4-pyridyl-alanine (3-Pal and 4-Pal) enhanced aqueous solubility of
glucagon while maintaining biological properties. Relative to native hormone,
analogue 9 (Gcg[3-Pal6,10,13, Aib16]) demonstrated superior biophysical
character, better suitability for medicinal purposes, and comparable pharmacology
against insulin-induced hypoglycemia in rats and pigs. Our data indicate that Pal
is a versatile surrogate to natural aromatic amino acids and can be employed as
an alternative or supplement with isoelectric adjustment to refine the
biophysical character of peptide drug candidates.
PMID- 27509199
TI - Rock Outcrops Redistribute Organic Carbon and Nutrients to Nearby Soil Patches in
Three Karst Ecosystems in SW China.
AB - Emergent rock outcrops are common in terrestrial ecosystems. However, little
research has been conducted regarding their surface function in redistributing
organic carbon and nutrient fluxes to soils nearby. Water that fell on and ran
off 10 individual rock outcrops was collected in three 100 * 100 m plots within a
rock desertification ecosystem, an anthropogenic forest ecosystem, and a
secondary forest ecosystem between June 2013 and June 2014 in Shilin, SW China.
The concentrations of total organic carbon (TOC), total nitrogen (N), total
phosphorus (P), and potassium (K) in the water samples were determined during
three seasons, and the total amounts received by and flowing out from the
outcrops were calculated. In all three ecosystems, TOC and N, P, and K were found
throughout the year in both the water received by and delivered to nearby soil
patches. Their concentrations and amounts were generally greater in forested
ecosystems than in the rock desertification ecosystem. When rock outcrops
constituted a high percentage (>= 30%) of the ground surface, the annual export
of rock outcrop runoff contributed a large amount of organic carbon and N, P, and
K nutrients to soil patches nearby by comparison to the amount soil patches
received via atmospheric deposition. These contributions may increase the spatial
heterogeneity of soil fertility within patches, as rock outcrops of different
sizes, morphologies, and emergence ratios may surround each soil patch.
PMID- 27509200
TI - Structure of polysaccharide moiety of Pseudomonas xanthomarina KMM 1447T
lipopolysaccharide.
AB - The structural analysis of a polysaccharide moiety of Pseudomonas xanthomarina
KMM 1447T lipopolysaccharide (LPS) was carried out. Mild acid degradation of LPS
resulted in identification of two polysaccharides. The major one was built of
beta-D-GlcpNAcA residues amidated with L-Ala and Gly residues randomly. The minor
polysaccharide was composed of branched tetrasaccharide repeating units
constituted by two D-Galr, D-GalpNAc and ether of D-Glc with (2R,4R)-2,4
dihydroxypentanoic acid lactone (2R,4R-Dhpl): ->3)-alpha-D-Galr-(1 -> 3)-beta-D
Galr-(1 -> 3)-[beta-D-Glcp4(2R,4R-Dhpl)-(1 -> 4)]-beta-D-GalpNAc-(1 -> .
PMID- 27509201
TI - Structure of repeating unit of the capsular polysaccharide from Acinetobacter
baumannii D78 and assignment of the K4 gene cluster.
AB - The structure of the K4 capsular polysaccharide (CPS) from a multiply antibiotic
resistant Acinetobacter baumannii isolate D78 was elucidated by chemical and
spectroscopical analysis. The K4 repeating unit is composed entirely by
aminosugars and the trisaccharide repeating unit of the backbone polysaccharide
is branched with a terminal N-acetyl-galactosamine capped with pyruvate as cyclic
acetal. Each residue is in the pyranose form, alpha configured at the anomeric
center, and has the D absolute configuration. The genes responsible for the
synthesis of the K4 repeat unit and its polymerization and export are found in
the capsule locus KL4 present in D78. The pyruvate acetal addition to
galactosamine is formed by Ptr1, a novel pyruvate transferase, encoded at this
locus.
PMID- 27509202
TI - The Relationship between the Clinical Progression of Benign Prostatic Hyperplasia
and Metabolic Syndrome: A Prospective Study.
AB - OBJECTIVE: To investigate whether metabolic syndrome (MetS) may be associated
with the clinical progression of benign prostatic hyperplasia (BPH). METHODS: A
total of 525 community-dwelling men (aged 45-78) with lower urinary tract
symptoms (LUTS) who had complete data at 3-year follow-up were included in this
prospective study. International Prostate Symptom Score (IPSS) questionnaire,
prostate ultrasonography for prostate volume (PV), maximum urine flow rate (Qmax)
and biological parameters were recorded. Participants were divided into a BPH
with the MetS group and a BPH without the MetS group, and all received a 3-year
follow-up to monitor possible correlations between LUTS/BPH clinical progression
and MetS. RESULTS: The results showed that MetS was associated with IPSS, Qmax
and PV (p < 0.05) after 3-year follow-up. The mean change of IPSS, PV and Qmax
were positively and negatively correlated with time in the BPH with MetS group
during the 3-year follow-up. In addition, the BPH clinical progression rate was
significantly higher in the BPH with MetS group, compared with the BPH without
MetS group (p < 0.05). Diabetes mellitus (DM) and hypertension were related to
increased risk of BPH clinical progression. CONCLUSIONS: The present results
suggest that MetS, in particular, DM and hypertension, may accelerate the
clinical progression of BPH in community-dwelling middle-aged and older men.
PMID- 27509204
TI - Quantitation of the DNA Adduct of Semicarbazide in Organs of Semicarbazide
Treated Rats by Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry:
A Comparative Study with the RNA Adduct.
AB - Semicarbazide is a widespread food contaminant that is produced by multiple
pathways. However, the toxicity of semicarbazide to human health remains unclear.
Using a highly accurate and sensitive isotope-dilution liquid chromatography
tandem mass spectrometry method, we identified and quantitated in this study for
the first time the DNA and RNA adduct of semicarbazide in DNA/RNA isolated from
the internal organs of semicarbazide-exposed rats. The analysis revealed a dose
dependent formation of the adducts in the internal organs of the semicarbazide
dosed rats and with the highest adduct levels identified in the stomach and small
intestine. Furthermore, results showed significantly higher levels of the RNA
adduct (4.1-7.0 times) than that of the DNA adducts. By analyzing DNA/RNA samples
isolated from rat organs in semicarbazide-dosed rats at different time points
postdosing, the adduct stability in vivo was also investigated. These findings
suggest that semicarbazide could have exerted its toxicity by affecting both the
transcription and translation processes of the cell.
PMID- 27509203
TI - Relationship of Physical Intimate Partner Violence with Mental Health Diagnoses
in the Nationwide Emergency Department Sample.
AB - OBJECTIVES: We examined associations of physical intimate partner violence (PIPV)
with selected mental health disorders using a nationally representative sample of
emergency department (ED) discharges corresponding to men and women (18-64 years)
from the 2010 Nationwide Emergency Department Sample. METHODS: PIPV was
determined using International Classification of Disease, 9th Revision, Clinical
Modification (ICD-9-CM) external cause of injury code E967.3 (battering by spouse
or partner). ICD-9-CM clinical classification of discharge diagnoses was used to
identify mental health disorders. Multivariable logistic regression models were
constructed to estimate adjusted odds ratios (ORadj) and their 95% confidence
intervals (CIs). RESULTS: PIPV prevalence was estimated at 0.36 per 1000 ED
discharges. The strongest correlates of PIPV were alcohol-related (ORadj = 3.02,
95% CI: 2.62-3.50), adjustment (ORadj = 2.37, 95% CI: 1.56-3.58), intentional
self-harm (ORadj = 1.41, 95% CI: 1.05-1.89), anxiety (ORadj = 1.23, 95% CI: 1.07
1.40), drug-related (ORadj = 1.22, 95% CI: 1.01-1.47), and mood (ORadj = 1.16,
95% CI: 1.04-1.31) disorders. PIPV's association with alcohol-related disorders
was stronger among women (ORadj = 3.22, 95% CI: 2.79-3.72) versus men (ORadj =
1.98, 95% CI: 1.42-2.77). Similarly, drug-related disorders were stronger
correlates of PIPV among women (ORadj = 1.32, 95% CI: 1.09-1.60) versus men
(ORadj = 0.59, 95% CI: 0.31-1.16). CONCLUSIONS: In EDs, PIPV was linked to
several mental health disorders, with women experiencing comorbid PIPV and
substance use more frequently than men.
PMID- 27509205
TI - The Characteristics and Prognostic Effect of E-Cadherin Expression in Colorectal
Signet Ring Cell Carcinoma.
AB - PURPOSE: Signet ring cell carcinoma (SRCC) is rare. The aim of this study is to
understand the clinicopathological features and identify the possible prognostic
factors in colorectal SRCC. METHODS: Patients with SRCC who underwent primary
lesion resection at Fudan University Shanghai Cancer Center from September 2008
to July 2014 were retrospectively analyzed. Patient's gender, age, tumor
location, depth of invasion, lymph node metastasis, synchronous distant
metastasis, perineural invasion, lymphovascular invasion, and E-cadherin
expression were studied with prognosis, and the correlation between E-cadherin
expression and clinicopathological features were analyzed. All
clinicopathological and molecular factors were put into multivariate analysis
using Cox proportional hazards model for detecting independent prognostic
factors. RESULTS: 59 patients accounting for 0.89% of total colorectal cancer
patients met the criteria and were enrolled in the study. The median survival
time is 28.9 months, and the 3-year survival rate is 62.7%. SRCC were seen more
common in young male patients. Advanced stage was more common in SRCC, 58 (98.3%)
patients had T3/T4 lesions, 52 (88.1%) patients had lymph node metastasis, and 14
(23.7%) patients had distant metastasis. Distant metastases were seen more common
in peritoneal cavity. Distant metastasis (HR = 4.194, 95% CI: 1.297-13.567),
lymphovascular invasion (HR = 2.888, 95% CI: 1.115-7.483), and E-cadherin
expression (HR = 0.272, 95% CI: 0.096-0.768) were independent predictors for
survival. CONCLUSIONS: SRCC is a rare subtype of colorectal cancer with poor
prognosis. Distant metastasis, lymphovascular invasion, and E-cadherin expression
can predict prognosis of colorectal SRCCs independently. More precise therapy and
more close surveillance are needed for these patients.
PMID- 27509206
TI - A Picea crassifolia Tree-Ring Width-Based Temperature Reconstruction for the Mt.
Dongda Region, Northwest China, and Its Relationship to Large-Scale Climate
Forcing.
AB - The historical May-October mean temperature since 1831 was reconstructed based on
tree-ring width of Qinghai spruce (Picea crassifolia Kom.) collected on Mt.
Dongda, North of the Hexi Corridor in Northwest China. The regression model
explained 46.6% of the variance of the instrumentally observed temperature. The
cold periods in the reconstruction were 1831-1889, 1894-1901, 1908-1934 and 1950
1952, and the warm periods were 1890-1893, 1902-1907, 1935-1949 and 1953-2011.
During the instrumental period (1951-2011), an obvious warming trend appeared in
the last twenty years. The reconstruction displayed similar patterns to a
temperature reconstruction from the east-central Tibetan Plateau at the inter
decadal timescale, indicating that the temperature reconstruction in this study
was a reliable proxy for Northwest China. It was also found that the
reconstruction series had good consistency with the Northern Hemisphere
temperature at a decadal timescale. Multi-taper method spectral analysis detected
some low- and high-frequency cycles (2.3-2.4-year, 2.8-year, 3.4-3.6-year, 5.0
year, 9.9-year and 27.0-year). Combining these cycles, the relationship of the
low-frequency change with the Pacific Decadal Oscillation (PDO), North Atlantic
Oscillation (NAO) and Southern Oscillation (SO) suggested that the reconstructed
temperature variations may be related to large-scale atmospheric-oceanic
variations. Major volcanic eruptions were partly reflected in the reconstructed
temperatures after high-pass filtering; these events promoted anomalous cooling
in this region. The results of this study not only provide new information for
assessing the long-term temperature changes in the Hexi Corridor of Northwest
China, but also further demonstrate the effects of large-scale atmospheric
oceanic circulation on climate change in Northwest China.
PMID- 27509207
TI - New Mechanistic Pathways for Criegee-Water Chemistry at the Air/Water Interface.
AB - Understanding Criegee chemistry has become one of central topics in atmospheric
research recently. The reaction of Criegee intermediates with gas-phase water
clusters has been widely viewed as a key Criegee reaction in the troposphere.
However, the effect of aerosols or clouds on Criegee chemistry has received
little attention. In this work, we have investigated the reaction between the
smallest Criegee intermediate, CH2OO, and water clusters in the gas phase, as
well as at the air/water surface using ab initio quantum chemical calculations
and adaptive buffered force quantum mechanics/molecular mechanics (QM/MM)
dynamics simulations. Our simulation results show that the typical time scale for
the reaction of CH2OO with water at the air/water interface is on the order of a
few picoseconds, 2-3 orders of magnitude shorter than that in the gas phase.
Importantly, the adbf-QM/MM dynamics simulations suggest several reaction
pathways for the CH2OO + water reaction at the air/water interface, including the
loop-structure-mediated mechanism and the stepwise mechanism. Contrary to the
conventional gas-phase CH2OO reaction, the loop-structure is not a prerequisite
for the stepwise mechanism. For the latter, a water molecule and the CH2OO at the
air/water interface, upon their interaction, can result in the formation of
(H3O)(+) and (OH)CH2(OO)(-). Thereafter, a hydrogen bond can be formed between
(H3O)(+) and the terminal oxygen atom of (OH)CH2(OO)(-), leading to direct proton
transfer and the formation of alpha-hydroxy methylperoxide, HOCH2OOH. The
mechanistic insights obtained from this simulation study should motivate future
experimental studies of the effect of water clouds on Criegee chemistry.
PMID- 27509208
TI - Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement
Component C5a.
AB - Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated
to inhibit CC chemokine-induced immune cell migration. In line with this, we
found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow
derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting
chemotaxis to a broader range of chemoattractants remains largely unexplored. As
our initial experiments demonstrated that RAW264.7 and BMDMs expressed high
levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the
effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a,
a complement peptide that plays a major role in multiple inflammatory
pathologies. Treatment of RAW264.7 macrophages, BMDMs and human monocytes with
netrin-1 inhibited their chemotaxis towards C5a, as measured using two different
real-time methods. This inhibitory effect was found to be dependent on netrin-1
receptor signalling, as an UNC5b blocking antibody was able to reverse netrin-1
inhibition of C5a induced BMDM migration. Treatment of BMDMs with netrin-1 had no
effect on C5aR1 proximal signalling events, as surface C5aR1 expression,
internalisation and intracellular Ca2+ release following C5aR1 ligation remained
unaffected after netrin-1 exposure. We next examined receptor distal events that
occur following C5aR1 activation, but found that netrin-1 was unable to inhibit
C5a induced phosphorylation of ERK1/2, Akt and p38, pathways important for
cellular migration. Furthermore, netrin-1 treatment had no effect on BMDM
cytoskeletal rearrangement following C5a stimulation as determined by microscopy
and real-time electrical impedance sensing. Taken together these data highlight
that netrin-1 inhibits monocyte and macrophage cell migration, but that the
mechanism behind this effect remains unresolved. Nevertheless, netrin-1 and its
cognate receptors warrant further investigation as they may represent a potential
avenue for the development of novel anti-inflammatory therapeutics.
PMID- 27509210
TI - Gender differences in the effect of grief reactions and burnout on emotional
distress among clinical oncologists.
AB - BACKGROUND: The current study was conducted to examine gender differences in the
effect of grief reactions and burnout on emotional distress among clinical
oncologists. METHODS: The participants included a convenience sample of 178
oncologists from Israel (52 of whom were women) and Canada (48 of whom were
women). Oncologists completed a questionnaire package that included a
sociodemographic survey, the General Health Questionnaire, a burnout measure, and
the Adult Oncologists Grief Questionnaire. To examine the effect of grief
reactions and burnout on emotional distress while controlling for country and
past depression within each gender, 2 hierarchical linear regression analyses
were computed. RESULTS: Female oncologists reported significantly more grief
responses to patient death (mean, 47.72 [standard deviation (SD), 8.71] and mean,
44.53 [SD, 9.19], respectively), more emotional distress (mean, 12.41 [SD, 4.36]
and mean, 10.64 [SD, 3.99], respectively), and more burnout (mean, 2.59 [SD,
1.69] and mean, 1.84 [SD, 1.5], respectively). For both genders, higher levels of
grief reactions were associated with greater emotional distress among those who
reported high levels of burnout (P<.001). However, for men, the association
between grief reactions and emotional distress also was documented at moderate
levels of burnout (P<.001). CONCLUSIONS: Patient death is a regular part of
clinical oncology. It is essential that oncologists be able to cope effectively
with this aspect of their work. The findings of the current study highlight the
need to take into account the cumulative stressors that oncologists contend with
when designing supportive interventions. Gender differences in burnout, reactions
to patient death, and emotional distress need to be addressed to ensure the best
quality of life for oncologists and the best quality of care for their patients.
Cancer 2016;122:3705-14. (c) 2016 American Cancer Society.
PMID- 27509209
TI - The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute
Ischaemic Stroke: A Combined Experimental and Theoretical Study.
AB - The neocortex and thalamus provide a core substrate for perception, cognition,
and action, and are interconnected through different direct and indirect pathways
that maintain specific dynamics associated with functional states including
wakefulness and sleep. It has been shown that a lack of excitation, or enhanced
subcortical inhibition, can disrupt this system and drive thalamic nuclei into an
attractor state of low-frequency bursting and further entrainment of thalamo
cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question
remains however whether similar TCD-like phenomena can arise with a cortical
origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical
interactions through an attenuation of the excitatory drive onto the thalamus,
creating an imbalance between excitation and inhibition that can lead to a state
of TCD. Here we tested this hypothesis by comparing the resting-state EEG
recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age
matched control-subjects (N = 17). We observed that these patients displayed the
hallmarks of TCD: a characteristic downward shift of dominant alpha-peaks in the
EEG power spectra, together with increased power over the lower frequencies
(delta and theta-range). Contrary to general observations in TCD, the patients
also displayed a broad reduction in beta-band activity. In order to explain the
genesis of this stroke-induced TCD, we developed a biologically constrained model
of a general thalamo-cortical module, allowing us to identify the specific
cellular and network mechanisms involved. Our model showed that a lesion in the
cortical component leads to sustained cell membrane hyperpolarization in the
corresponding thalamic relay neurons, that in turn leads to the de-inactivation
of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a
pathological bursting regime. This thalamic bursting synchronises activity on a
population level through divergent intrathalamic circuits, and entrains thalamo
cortical pathways by means of propagating low-frequency oscillations beyond the
restricted region of the lesion. Hence, pathological stroke-induced thalamo
cortical dynamics can be the source of diaschisis, and account for the
dissociation between lesion location and non-specific symptoms of stroke such as
neuropathic pain and hemispatial neglect.
PMID- 27509211
TI - Branched Fatty Acid Esters of Hydroxy Fatty Acids Are Preferred Substrates of the
MODY8 Protein Carboxyl Ester Lipase.
AB - A recently discovered class of endogenous mammalian lipids, branched fatty acid
esters of hydroxy fatty acids (FAHFAs), possesses anti-diabetic and anti
inflammatory activities. Here, we identified and validated carboxyl ester lipase
(CEL), a pancreatic enzyme hydrolyzing cholesteryl esters and other dietary
lipids, as a FAHFA hydrolase. Variants of CEL have been linked to maturity-onset
diabetes of the young, type 8 (MODY8), and to chronic pancreatitis. We tested the
FAHFA hydrolysis activity of the CEL MODY8 variant and found a modest increase in
activity as compared with that of the normal enzyme. Together, the data suggest
that CEL might break down dietary FAHFAs.
PMID- 27509212
TI - Fear of Cancer Recurrence and Its Impacts on Quality of Life in Family Caregivers
of Patients With Head and Neck Cancers.
AB - BACKGROUND: Fear of cancer recurrence (FCR) is a major concern for family
caregivers (FCs) caring for patients with head and neck cancers (HNCs). PURPOSE:
This study (a) investigated the FCR experience of HNC FCs, (b) compared the
differences in the FCR levels of FCs while taking care of patients with different
lengths of time since completing major treatments (posttreatment durations), and
(c) examined the correlation between FCR and quality of life (QOL) in these FCs.
METHODS: A cross-sectional study was conducted in the radiation outpatient
department of a medical center in northern Taiwan. A set of questionnaires,
including the Fear of Cancer Recurrence Inventory-Caregiver version and the
Medical Outcomes Short-Form Health Survey, and a background information form were
employed. One-way analysis of variance was used to examine the differences in the
FCR and QOL among groups of FCs taking care of patients with different
posttreatment durations (typically concurrent chemoradiotherapy). Pearson's
correlation was used to identify the relationship between FCR and QOL. RESULTS:
Two hundred fifty FCs were recruited in this study. The FCs used several coping
and reassurance strategies to address their FCR experiences. Those FCs who cared
for patients with short posttreatment durations (3-6 and 6-12 months) showed
significantly higher overall FCR levels and higher FCR severity levels than those
who cared for patients with long posttreatment durations (more than 5 years).
High FCR was negatively correlated with physical and mental QOL.
CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The results suggest that FCs caring for
patients with a relatively short posttreatment duration experience higher levels
of FCR than those caring for patients with a longer posttreatment duration. In
clinical settings, healthcare providers should use posttreatment duration as an
indicator of risk of FCR in caregivers to address FCR and provide appropriate
support. Future research should develop and examine interventions to help HNC FCs
cope effectively with their FCR and improve their QOL.
PMID- 27509213
TI - Oxytetracycline Delivery in Adult Female Zebrafish by Iron Oxide Nanoparticles.
AB - Recently, the indiscriminate use of antibiotics in the aquaculture sector has
raised public concern because of possible toxic effects, development of bacterial
resistance, and accumulation of residues in individual tissues. Even if several
countries have developed regulations about their use, it is clear that long-term
growth of the aquaculture industry requires both ecologically sound practices and
sustainable resource management. Alternative strategies for better management of
antibiotic administration are of primary interest to improve absorption rates
and, as a consequence, to reduce their release into the aquatic environment. The
present study investigates, for the first time to our knowledge, a new
methodology for oxytetracycline (OTC) administration through the use of iron
oxide nanoparticles (NPs) (made of maghemite gamma-Fe2O3) in zebrafish (Danio
rerio). Fish were divided into 4 experimental groups: control; group A exposed to
4 mg/L OTC (through water); group B exposed to the 100 mg/L SAMNs@OTC complex
(equivalent to 4 mg/L OTC), and group C exposed to bare NPs. No detoxification
processes or anatomical alterations were observed in fish exposed to bare NPs.
Exposure of fish to the SAMNs@OTC complex resulted in a 10 times higher OTC
accumulation with respect to using water exposure. This new OTC administration
method seems much more efficient with respect to the traditional way of exposure
and has the potentiality to reduce antibiotic utilization and possible
environmental impacts. However, the dynamics related to OTC release from the
SAMNs@OTC complex are still not clear and need further investigations.
PMID- 27509214
TI - The use of leucocyte and platelet-rich fibrin in socket management and ridge
preservation: a split-mouth, randomized, controlled clinical trial.
AB - AIM: To investigate the influence of the use L-PRF as a socket filling material
and its ridge preservation properties. MATERIALS AND METHODS: Twenty-two patients
in need of single bilateral and closely symmetrical tooth extractions in the
maxilla or mandible were included in a split-mouth RCT. Treatments were randomly
assigned (L-PRF socket filling versus natural healing). CBCT scans were obtained
after tooth extraction and three months. Scans were evaluated by superimposition
using the original DICOM data. Mean ridge width differences between timepoints
were measured at three levels below the crest on both the buccal and lingual
sides (crest -1 mm (primary outcome variable), -3 mm and -5 mm). RESULTS: Mean
vertical height changes at the buccal were -1.5 mm (+/-1.3) for control sites and
0.5 mm (+/-2.3) for test sites (p < 0.005). At the buccal side, control sites
values were, respectively, -2.1 (+/-2.5), -0.3 mm (+/-0.3) (p < 0.005) and -0.1
mm (+/-0.0), and test sites values were, respectively, -0.6 mm (+/-2.2) (p <
0.005), -0.1 mm (+/-0.3) and 0.0 mm (+/-0.1). Significant differences (p < 0.005)
were found for total width reduction between test (-22.84%) and control sites (
51.92%) at 1 mm below crest level. Significant differences were found for socket
fill (visible mineralized bone) between test (94.7%) and control sites (63.3%).
CONCLUSION: The use of L-PRF as a socket filling material to achieve preservation
of horizontal and vertical ridge dimension at three months after tooth
extraction is beneficial.
PMID- 27509215
TI - Rotational Dynamics in Ionic Liquids from NMR Relaxation Experiments and
Simulations: Benzene and 1-Ethyl-3-Methylimidazolium.
AB - Temperature-dependent (2)H longitudinal spin relaxation times (T1) of dilute
benzene-d6 in 1-butyl-3-methylimidazolium tetrafluoroborate ([Im41][BF4]) and two
deuterated variants of the 1-ethyl-3-methylimidazolium cation (Im21(+)-d1 and
Im21(+)-d6) in 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
([Im21][Tf2N]), measured at multiple Larmor frequencies, were used to probe
rotational dynamics in ionic liquids. Rotational correlation times significantly
faster than predicted by slip hydrodynamic calculations were observed for both
solutes. Molecular dynamics simulations of these systems enabled extraction of
more information about the rotational dynamics from the NMR data than rotation
times alone. The multifrequency (2)H T1(T) data could be fit to within
uncertainties over a broad region about the T1 minimum using models of the
relevant rotational time correlation functions and their viscosity/temperature
dependence derived from simulation. Such simulation-guided fitting provided
confidence in the semiquantitative accuracy of the simulation models and enabled
interpretation of NMR measurements to higher viscosities than previously
possible. Simulations of the benzene system were therefore used to explore the
nature of solute rotation in ionic liquids and how it might differ from rotation
in conventional solvents. Whereas "spinning" about the C6 axis of benzene senses
similarly weak solvent friction in both types of solvents, "tumbling" (rotations
about in-plane axes) differs significantly in conventional solvents and ionic
liquids. In the sluggish environment provided by ionic liquids, orientational
caging and the presence of rare but influential large-amplitude (180 degrees )
jumps about in-plane axes lead to rotations being markedly nondiffusive,
especially below room temperature.
PMID- 27509216
TI - Reproductive phenology of Mauritia flexuosa L. (Arecaceae) in a coastal restinga
environment in northeastern Brazil.
AB - The buriti, Mauritia flexuosa, is the most common palm in Brazil, where it has
considerable ecological and economic importance. However, few data are available
on the phenology of the species, mainly in coastal restinga ecosystems. The
present study monitored the reproductive phenology of M. flexuosa in the restinga
of Barreirinhas, in the Brazilian Northeast, and investigated the relationship
between phenophases and climatic variables. The presence/absence of flowers and
fruits was recorded monthly in 25 individuals of each sex between August, 2009,
and October, 2012. There was no difference in the phenology of male and female
specimens, with flowering and fruiting occurring exclusively in the dry season.
We believe that the specific abiotic characteristics of the study environment,
such as the intense sunlight and availability of water in the soil, contribute to
the reproductive success of M. flexuosa in the dry season, with consequent
germination and establishment of seedlings occurring during the subsequent rainy
season.
PMID- 27509217
TI - Physiological response of invasive mussel Limnoperna fortunei (Dunker, 1857)
(Bivalvia: Mytilidae) submitted to transport and experimental conditions.
AB - Successful animal rearing under laboratory conditions for commercial processes or
laboratory experiments is a complex chain that includes several stressors (e.g.,
sampling and transport) and incurs, as a consequence, the reduction of natural
animal conditions, economic losses and inconsistent and unreliable biological
results. Since the invasion of the bivalve Limnoperna fortunei (Dunker, 1857) in
South America, several studies have been performed to help control and manage
this fouling pest in industrial plants that use raw water. Relatively little
attention has been given to the laboratory rearing procedure of L. fortunei, its
condition when exposed to a stressor or its acclimation into laboratory
conditions. Considering this issue, the aims of this study are to (i) investigate
L. fortunei physiological responses when submitted to the depuration process and
subsequent air transport (without water/dry condition) at two temperatures, based
on glycogen concentrations, and (ii) monitor the glycogen concentrations in
different groups when maintained for 28 days under laboratory conditions. Based
on the obtained results, depuration did not affect either of the groups when they
were submitted to approximately eight hours of transport. The variation in
glycogen concentration among the specimens that were obtained from the field
under depurated and non-depurated conditions was significant only in the first
week of laboratory growth for the non-depurated group and in the second week for
the depurated group. In addition, the tested temperature did not affect either of
the groups that were submitted to transport. The glycogen concentrations were
similar to those of the specimens that were obtained from the field in third
week, which suggests that the specimens acclimated to laboratory conditions
during this period of time. Thus, the results indicate that the air transport and
acclimation time can be successfully incorporated into experimental studies of L.
fortunei. Finally, the tolerance of L. fortunei specimens to the stressor tested
herein can help us understand the invasive capacity of this mussel during the
establishment process.
PMID- 27509218
TI - Phenolic Compounds of Pomegranate Byproducts (Outer Skin, Mesocarp, Divider
Membrane) and Their Antioxidant Activities.
AB - Pomegranate peel was separated into outer leathery skin (PS), mesocarp (PM), and
divider membrane (PD), and its phenolic compounds were extracted as free (F),
esterified (E), and insoluble-bound (B) forms for the first time. The total
phenolic content followed the order PD > PM > PS. ABTS(*+), DPPH, and hydroxyl
radical scavenging activities and metal chelation were evaluated. In addition,
pomegranate peel extracts showed inhibitory effects against alpha-glucosidase
activity, lipase activity, and cupric ion-induced LDL-cholesterol oxidation as
well as peroxyl and hydroxyl radical-induced DNA scission. Seventy-nine phenolic
compounds were identified using HPLC-DAD-ESI-MS(n) mainly in the form of
insoluble-bound. Thirty compounds were identified for the first time. Gallic acid
was the major phenolic compound in pomegranate peel, whereas kaempferol 3-O
glucoside was the major flavonoid. Moreover, ellagic acid and monogalloyl
hexoside were the major hydrolyzable tannins, whereas the dominant
proanthocyanidin was procyanidin dimers. Proanthocyanidins were detected for the
first time.
PMID- 27509219
TI - Coronary angiography after successful thrombolysis - Is the recommended time
interval of 24h an important issue?
AB - INTRODUCTION: Percutaneous coronary intervention (PCI) is currently considered
the gold-standard treatment of acute coronary syndromes with ST-segment elevation
(STEMI). However, this is not the reality of many European centers, where
thrombolysis is performed as primary therapy. AIMS: To determine, in a STEMI
population that performed successful fibrinolytic treatment, if the performance
of coronary angiography after the first 24h was associated with more hospital
complications, including higher mortality, compared with its performance in the
recommended time. METHODS: Retrospective study, including 1065 patients with
STEMI, who performed successful thrombolysis. The population was divided in three
groups: A, patients who didn't undergo coronary angiography after successful
thrombolysis (n=278; 26.1%); B, patients who underwent coronary angiography in
the first 24h after successful thrombolysis (n=127; 11.9%); and C, patients who
underwent angiography after the first 24h (n=660; 62.0%). Groups were compared
regarding their characteristics and in-hospital complications. RESULTS: Groups B
and C had more male patients and had younger patients than group A. Group A
presented higher Killip classes at admission, more severe left ventricle
dysfunction and a higher number of complications during hospitalization. Logistic
regression revealed that: 1) the non-performance of coronary angiography after
thrombolysis was an independent predictor of in-hospital mortality; and 2) the
performance of angiography after the recommended time wasn't associated with
higher mortality. CONCLUSIONS: Coronary angiography after thrombolysis
constitutes an important strategy, whose non-performance carries worse prognosis.
The time interval currently recommended of 24h seems clinically acceptable;
however, its realization outside the recommended time doesn't seem to lead to
higher mortality.
PMID- 27509220
TI - Prevalence, determinants, and prognostic significance of delirium in patients
with acute heart failure.
AB - BACKGROUND: Delirium is a serious syndrome in critically ill patients. However,
the prognostic impact of delirium and its determinants in acute heart failure
(AHF) patients have not been fully elucidated. METHODS: We examined 611 AHF
patients who were admitted to our institution. Delirium was diagnosed based on
the Intensive Care Delirium Screening Checklist (ICDSC). RESULTS: Delirium
developed in 139 patients (23%) during hospitalization. Patients with delirium
had higher incidence of non-cardiovascular death (p=0.046) and worsening heart
failure (p<0.001) during hospitalization. Among patients who survived at
discharge, the incidence of all-cause death, cardiovascular death and non
cardiovascular death after discharge were significantly higher in patients with
delirium than those without (log-rank; p<0.001, p=0.001, p<0.001, respectively)
during a median follow-up period of 335days. In multivariable model, the
development of delirium was an independent determinant of worsening heart failure
during hospitalization (OR: 2.44, 95% CI: 1.27-4.63) and all-cause death after
discharge (HR: 2.38, 95% CI: 1.30-4.35). Furthermore, multivariate analysis
indicated that history of cerebrovascular disease (OR: 2.13, 95% CI: 1.36-3.35),
age (OR: 1.43, 95% CI: 1.15-1.80), log BNP (OR: 1.39, 95% CI: 1.09-1.79), serum
albumin (OR: 0.84, 95% CI: 0.76-0.93) and blood glucose levels (OR: 1.03, 95% CI:
1.00-1.06) were independent determinants of delirium. CONCLUSION: In patients
with AHF, the development of delirium was associated with poor clinical outcomes,
suggesting the importance of early screening and careful monitoring of delirium
in such patients.
PMID- 27509221
TI - Plasma levels of oxidative stress-responsive apoptosis inducing protein (ORAIP)
in patients with atrial fibrillation.
PMID- 27509222
TI - The association between in-hospital hemoglobin changes, cardiovascular events,
and mortality in acute decompensated heart failure: Results from the ESCAPE
trial.
AB - INTRODUCTION: The effect of acute changes of hemoglobin during index heart
failure admission on long-term outcomes remains unknown. METHODS: We examined 433
patients enrolled in the ESCAPE trial. RESULTS: Of the 433 patients, 324 (75%)
had baseline and discharge hemoglobin available for analysis. Of those, 64 (20%)
had at least 1g/dL drop of hemoglobin by time of discharge. Compared to patients
without hemoglobin changes (g/dL), patients with hemoglobin drop were older (59
vs. 55, p=0.011), had lower systolic BP (mmHg) (99 vs. 106, p=0.017), lower
sodium (mg/dL) (136 vs. 137 (mg/dL), p=0.025), higher BUN (mg/dL) (37 vs. 26,
p<0.001), higher creatinine (mg/dL) (1.6 vs. 1.3, p<0.001) and higher hospital
length of stay (10days vs. 6days, p=<0.001). Higher hemoglobin drop was observed
in the pulmonary artery catheter (PACs) (vs. clinical care) randomized arm of the
trial (2g/dL: 10% versus 3%, p=0.010; 3g/dL: 5% versus 0%, p=0.005). After
adjustments, a drop of hemoglobin with at least 1g/dL was associated with
increased mortality risk (Adjusted HR 2.38, p=0.003) and higher hemoglobin
concentrations by the time of discharge was associated with lower mortality rate
(Adjusted HR 0.79, p=0.003). PACs insertion was not associated with adverse
clinical outcomes by quartiles of % change of hemoglobin. However, PACs use was
an independent predictor of hemoglobin drop during heart failure admission
(Adjusted OR: Hb Drop 1g/dL: 1.88, p=0.043; Hb Drop 2g/dL: 3.6 p=0.025).
CONCLUSION: In-hospital decrease in hemoglobin is independently associated with
increased long-term mortality and hospital length of stay in ADHF. The ideal
hemoglobin levels in ADHF patients should be investigated and the insertion of
PACs to direct therapy should be weighed against bleeding risks.
PMID- 27509223
TI - CXCL13 inhibits microRNA-23a through PI3K/AKT signaling pathway in adipose tissue
derived-mesenchymal stem cells.
AB - OBJECTIVES: Adipose tissue derived-mesenchymal stem cells (AMSCs) are one of the
most widely used MSCs in the cell therapy for regenerative medicine. In the
current study, the role of CXCL13 in AMSCs and its potential signaling pathway
were investigated. METHODS: AMSCs were isolated from adipose tissue of healthy
subjects. After administrating the cells with CXCL13, the expression levels of
miR-23a and runt-related transcription factor 2 (Runx2) were assessed by real
time PCR and western blot. The alterations of phosphoinositide-3 kinase
(PI3K)/Akt, stress-activated protein kinase (SAPK)/c-jun kinase (JNK), and
extracellular-signal-regulated kinase (ERK1/2) pathways were also evaluated.
RESULTS: CXCL13 down-regulated miR-23a and up-regulated Runx2 expression in
AMSCs. The inhibitor specific for PI3K/AKT, but not SAPK/JNK and ERK ERK1/2,
reversed the effects of CXCL13 on miR-23a and Runx2 expression. CONCLUSION:
CXCL13 inhibits miR-23a expression through modulating PI3K/AKT pathway in AMSCs.
PMID- 27509224
TI - Ultrasound Identification of the Guidewire in the Brachiocephalic Vein for the
Prevention of Inadvertent Arterial Catheterization During Internal Jugular
Central Venous Catheter Placement.
AB - BACKGROUND: Imaging the guidewire with ultrasonography in the internal jugular
vein during central venous catheterization often is used to verify proper
guidewire placement and to aid in prevention of inadvertent arterial
catheterization. It is known, however, that inadvertent arterial catheterization
can occur despite imaging the guidewire in the internal jugular vein because the
guidewire may continue through the far wall of the internal jugular vein and into
an adjacent artery. We propose confirmation of the guidewire in the
brachiocephalic vein with ultrasonography as a more reliable method of confirming
proper guidewire placement. METHODS: A prospective feasibility study of 200 adult
cardiothoracic surgery patients undergoing internal jugular vein catheterization
was performed to determine whether the guidewire could be imaged with
ultrasonography in the brachiocephalic vein. The guidewire was imaged in the
internal jugular vein in a short-axis view, and the transducer was then angled
caudally under the clavicle, following the guidewire into the brachiocephalic
vein. RESULTS: The right internal jugular vein was catheterized in 193 patients
and the left internal jugular in 7 patients. The brachiocephalic vein was
successfully imaged in all but 2 patients. In 3 patients, the guidewire could not
be clearly identified in the brachiocephalic vein because of interference from
the leads of a heart rhythm device (pacemaker or defibrillator) or preexisting
catheter. In 2 patients, the guidewire was not seen initially in the
brachiocephalic vein because of coiling in the internal jugular vein, and in 1
patient because of the guidewire passing into the right subclavian vein, but all
3 were subsequently imaged in the brachiocephalic vein after repositioning.
CONCLUSIONS: During internal jugular vein catheterization, the brachiocephalic
vein was imaged with ultrasonography in 99% of patients (the lower 1-sided 99%
confidence limit is 96%). The guidewire was imaged in the brachiocephalic vein in
all cases except when leads from a heart rhythm device caused interference,
although in some patients with leads, the guidewire could be imaged without
difficulty. The absence of the guidewire from the brachiocephalic vein was
indicative of a malpositioned guidewire.
PMID- 27509225
TI - The Effect of Combined Spinal-Epidural Versus Epidural Analgesia in Laboring
Women on Nonreassuring Fetal Heart Rate Tracings: Systematic Review and Meta
analysis.
AB - BACKGROUND: Combined spinal-epidural labor analgesia has gained popularity, but
it is unclear whether this technique is associated with a higher incidence of
nonreassuring fetal heart rate (FHR) tracings compared with epidural analgesia.
Our meta-analysis aimed at comparing the incidence of nonreassuring FHR tracings
between the 2 neuraxial techniques. METHODS: Databases were searched to identify
randomized controlled trials that compared the incidence of nonreassuring FHR
tracings, as defined in the individual studies, after combined spinal-epidural
versus epidural analgesia in laboring women. Risk ratios (RRs) and 95% confidence
intervals (CIs) were calculated using the random-effects model. We performed a
subgroup analysis for studies using low-dose epidural bupivacaine concentrations
(<=0.125%) for epidural analgesia. RESULTS: Seventeen trials including 3947
parturients were retrieved that compared the 2 neuraxial techniques. All trials
used intrathecal opioids in 1 study arm. The pooled effect estimate of low- and
high-dose epidural bupivacaine studies together showed a significantly increased
risk of nonreassuring FHR tracings with the combined technique (RR 1.31, 95% CI
1.02-1.67, P = .03, I = 18%). A subgroup analysis of 10 trials using low-dose
epidural bupivacaine found a RR for nonreassuring FHR tracings between combined
spinal-epidural and epidural analgesia of 1.12, 95% CI 0.93-1.34, P = .18. In a
sensitivity analysis of those low-dose epidural bupivacaine studies that ensured
blinding of the outcome assessor, the RR was 1.41, 95% CI 0.99-2.02, P = .06.
CONCLUSIONS: Combined spinal-epidural labor analgesia was associated with a
higher risk of nonreassuring FHR tracings than epidural analgesia alone. In the
subgroup analysis comparing combined spinal-epidural with low-dose epidural labor
analgesia, the 95% CI contains a clinically significant difference between
groups; moreover, the 95% CI overlaps with the 95% CI of the comparison of the
combined low- and high-dose epidural techniques. Therefore, it cannot be
concluded that there was no difference between combined spinal-epidural and low
dose epidural techniques.
PMID- 27509226
TI - Hermann Dietz.
PMID- 27509227
TI - Lanthanoid Template Isolation of the alpha-1,5 Isomer of Dicobalt(II)-Substituted
Keggin Type Phosphotungstates: Syntheses, Characterization, and Magnetic
Properties.
AB - A new series of heterometallic 3d-4f sandwich type phosphotungstates,
[Ln{PCo2W10O38(H2O)2}2](11-) (Ln = Sm(III), Eu(III), Gd(III), Tb(III), Dy(III),
Ho(III), Er(III), Tm(III), Yb(III), and Lu(III), denoted 1a-10a, respectively),
have been synthesized by a one-pot reaction procedure on reacting the dilacunary
K14[P2W19O69(H2O)].24H2O precursor with Ln(NO3)3.nH2O and Co(NO3)2.6H2O in an
aqueous potassium chloride solution. All the compounds were isolated as potassium
salts and further characterized with different analytical techniques such as
single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, high
resolution electrospray ionization mass spectrometry, elemental analysis by
inductively coupled plasma atomic emission spectroscopy, magnetic measurement,
and thermogravimetric analysis. Single-crystal X-ray diffraction analysis of the
compounds reveals that all these compounds are isostructural and crystallized in
the orthorhombic crystal system in space group Iba2. The polyanions contain the
alpha-1,5 isomer of dicobalt-substituted alpha-Keggin phosphotungstate, which
sandwiched lanthanoid cation and formed novel heterometallic dimer species. The
temperature-dependent magnetic susceptibilities of 1a, 2a, 4a, and 7a-10a
indicate the dominant contribution of the ferromagnetic interaction between
Co(II) and Co(II) within the cluster, while the antiferromagnetic interaction
between Co(II) and Ln(III) dominates for 3a, 5a, and 6a. The isothermal
magnetizations of 1a-10a show a gradual increase in magnetization at low fields
and do not reach saturation even at 50 kOe.
PMID- 27509228
TI - Shape of allied health: an environmental scan of 27 allied health professions in
Victoria.
AB - Objective In 2015, the Victorian Department of Health and Human Services
commissioned the Victorian Allied Health Workforce Research Program to provide
data on allied health professions in the Victorian public, private and not-for
profit sectors. Herein we present a snapshot of the demographic profiles and
distribution of these professions in Victoria and discuss the workforce
implications. Methods The program commenced with an environmental scan of 27
allied health professions in Victoria. This substantial scoping exercise
identified existing data, resources and contexts for each profession to guide
future data collection and research. Each environmental scan reviewed existing
data relating to the 27 professions, augmented by an online questionnaire sent to
the professional bodies representing each discipline. Results Workforce data were
patchy but, based on the evidence available, the allied health professions in
Victoria vary greatly in size (ranging from just 17 child life therapists to 6288
psychologists), are predominantly female (83% of professions are more than 50%
female) and half the professions report that 30% of their workforce is aged under
30 years. New training programs have increased workforce inflows to many
professions, but there is little understanding of attrition rates. Professions
reported a lack of senior positions in the public sector and a concomitant lack
of senior specialised staff available to support more junior staff. Increasing
numbers of allied health graduates are being employed directly in private
practice because of a lack of growth in new positions in the public sector and
changing funding models. Smaller professions reported that their members are more
likely to be professionally isolated within an allied health team or larger
organisations. Uneven rural-urban workforce distribution was evident across most
professions. Conclusions Workforce planning for allied health is extremely
complex because of the lack of data, fragmented funding and regulatory frameworks
and diverse employment contexts. What is known about this topic? There is a lack
of good-quality workforce data on the allied health professions generally. The
allied health workforce is highly feminised and unevenly distributed
geographically, but there is little analysis of these issues across professions.
What does this paper add? The juxtaposition of the health workforce demographics
and distribution of 27 allied health professions in Victoria illustrates some
clear trends and identifies several common themes across professions. What are
the implications for practitioners? There are opportunities for the allied health
professions to collectively address several of the common issues to achieve
economies of scale, given the large number of professions and small size of many.
PMID- 27509229
TI - Putting pain out of mind with an 'out of body' illusion.
AB - BACKGROUND: Chronic pain is a growing societal concern that warrants scientific
investigation, especially given the ineffectiveness of many treatments. Given
evidence that pain experience relies on multisensory integration, there is
interest in using body ownership illusions for reducing acute pain. AIM: In the
present study, we investigate whether patients' experience of chronic pain could
be reduced by full body illusions (FBIs) that cause participants to dissociate
from their own body. METHODS: Participants with chronic pain (including sciatica,
osteoarthritis, fibromyalgia, muscular pain, IBS and back pain) viewed their own
'virtual' bodies via a video camera and head-mounted display for two minutes. In
the 'back-stroking FBI', their backs were stroked with a stick while they viewed
synchronous or asynchronous stroking on the virtual body and in the 'front
stroking FBI', they were stroked near their collarbone while viewing the stick
approach their field of view in a synchronous or asynchronous fashion. Illusion
strength and pain intensity were measured with self-report questionnaires.
RESULTS: We found that full body illusions were experienced by patients with
chronic pain and further, that pain intensity was reduced by an average of 37%
after illusion (synchronous) conditions. CONCLUSION: These findings add support
to theories that high-level multisensory body representations can interact with
homeostatic regulation and pain perception. SIGNIFICANCE: Pain intensity in
chronic pain patients was reduced by 37% by 'out of body' illusions. These data
demonstrate the potential of such illusions for the management of chronic pain.
PMID- 27509230
TI - Blood transfusion in preterm infants improves intestinal tissue oxygenation
without alteration in blood flow.
AB - BACKGROUND AND OBJECTIVE: The objective of the study was to investigate the
splanchnic blood flow velocity and oximetry response to blood transfusion in
preterm infants according to postnatal age. MATERIALS AND METHODS: Preterm
infants receiving blood transfusion were recruited to three groups: 1-7 (group 1;
n = 20), 8-28 (group 2; n = 21) and >=29 days of life (group 3; n = 18). Superior
mesenteric artery (SMA) peak systolic (PSV) and diastolic velocities were
measured 30-60 min pre- and post-transfusion using Doppler ultrasound scan.
Splanchnic tissue haemoglobin index (sTHI), tissue oxygenation index (sTOI) and
fractional tissue oxygen extraction (sFTOE) were measured from 15-20 min before
to post-transfusion using near-infrared spectroscopy. RESULTS: The mean
pretransfusion Hb in group 1, 2 and 3 was 11, 10 and 9 g/dl, respectively. The
mean (SD) pretransfusion SMA PSV in group 1, 2 and 3 was 0.63 (0.32), 0.81 (0.33)
and 0.97 (0.40) m/s, respectively, and this did not change significantly
following transfusion. The mean (SD) pretransfusion sTOI in group 1, 2 and 3 was
36.7 (19.3), 44.6 (10.4) and 41.3 (10.4)%, respectively. The sTHI and sTOI
increased (P < 0.01), and sFTOE decreased (P < 0.01) following transfusion in all
groups. On multivariate analysis, changes in SMA PSV and sTOI following blood
transfusion were not associated with PDA, feeding, pretransfusion Hb and mean
blood pressure. CONCLUSION: Pretransfusion baseline splanchnic tissue oximetry
and blood flow velocity varied with postnatal age. Blood transfusion improved
intestinal tissue oxygenation without altering mesenteric blood flow velocity
irrespective of postnatal ages.
PMID- 27509231
TI - Growth, Grazing, and Starvation Survival in Three Heterotrophic Dinoflagellate
Species.
AB - To assess the effects of fluctuating prey availability on predator population
dynamics and grazing impact on phytoplankton, we measured growth and grazing
rates of three heterotrophic dinoflagellate species-Oxyrrhis marina, Gyrodinium
dominans and Gyrodinium spirale-before and after depriving them of phytoplankton
prey. All three dinoflagellate species survived long periods (> 10 d) without
algal prey, coincident with decreases in predator abundance and cell size. After
1-3 wks, starvation led to a 17-57% decrease in predator cell volume and some
cells became deformed and transparent. When re-exposed to phytoplankton prey,
heterotrophs ingested prey within minutes and increased cell volumes by 4-17%. At
an equivalent prey concentration, continuously fed predators had ~2-fold higher
specific growth rates (0.18 to 0.55 d-1 ) than after starvation (-0.16 to 0.25 d
1 ). Maximum specific predator growth rates would be achievable only after a time
lag of at least 3 d. A delay in predator growth poststarvation delays predator
induced phytoplankton mortality when prey re-emerges at the onset of a bloom
event or in patchy prey distributions. These altered predator-prey population
dynamics have implications for the formation of phytoplankton blooms, trophic
transfer rates, and potential export of carbon.
PMID- 27509232
TI - Ultrasound-guided peripheral venous access for therapeutic apheresis procedures
reduces need for central venous catheters.
AB - Therapeutic and donor apheresis requires adequate vascular access to achieve
inlet flow rates of ~50-100 mL/min. While central dialysis-type venous catheters
can usually provide such access, their use includes several associated risks.
Some of these risks can be avoided or diminished if adequate peripheral venous
access can be established. Some patients have adequate peripheral veins for
apheresis that cannot be readily identified visually or by palpation. We
hypothesized that ultrasound-guided peripheral venous access would benefit such
patients and would lead to placement of fewer central venous catheters. The
technique of ultrasound-guided peripheral access for apheresis has been in use at
Houston Methodist Hospital since 2012. We performed a prospective review of
patients undergoing inpatient and outpatient apheresis at Houston Methodist
Hospital from July 1, 2015 to September 30, 2015, to assess its benefit. During
this time, we performed 831 procedures on 186 patients, including 787 therapeutic
plasma exchanges, three red blood cell exchanges, 41 peripheral stem cell
collections. Ultrasound-guided vascular access was used for 68 procedures (8% of
all procedures), including 62 therapeutic plasma exchanges, 4 peripheral stem
cell collections, and 2 red blood cell changes. Use of ultrasound-guided
peripheral access prevented the placement of central venous catheters in 37 (20%)
patients, demonstrating its utility in a busy transfusion service.
PMID- 27509233
TI - Identification of markers of cancer in urban sewage through the use of a suspect
screening approach.
AB - The administration of anticancer drugs during chemotherapy treatments has
increased considerably in recent years, and based on the growing incidence of
cancer worldwide there is a foreseen increase in their use over the coming years.
Many anticancer drugs are not removed by conventional wastewater treatment plants
(WWTPs) and can therefore reach the aquatic environment and potentially threaten
aquatic life. The objective of this work was to apply a suspect screening
methodology to detect chemotherapy and radiotherapy drugs and their related
compounds such metabolites and/or biomarkers in wastewater. The use of logical
pre-determined criteria to refine the suspect list down to a relatively small
number of relevant compounds greatly improved the efficiency of the analysis.
Mass accuracy, isotopic patterns and predicted retention time were used to
tentatively identify the suspects. Successful identification of cancer-related
suspects included two antineoplastic hormones, two X-ray contrast agents and a
pyrrolizidine alkaloid related to an herbal medicine. This is the first time that
a suspect screening paradigm has been successfully applied to the identification
of pharmaceuticals and biomarkers related to chemotherapy in wastewater.
PMID- 27509235
TI - Thrombotic Microangiopathy in the Setting of HIV Infection: A Case Report and
Review of the Differential Diagnosis and Therapy.
AB - Before the modern era of HIV/AIDS therapeutics, which enabled a cascade of early
recognition of infection, prompt initiation of effective antiretroviral
therapies, and close follow-up, severe forms of microvascular clotting disorders
known as thrombotic microangiopathies (TMAs) were frequent in the setting of
advanced HIV disease. Their incidence was as high as 7% in the period 1984-1999,
but fell dramatically, to <0.5%, by 2002. This profound change was predicated on
one critical development: availability of new classes of anti-HIV drugs, enabling
reduction and maintenance of HIV viral loads to undetectable levels. Another
development in the period 1999-2002 related to TMA therapy: with recognition of
autoantibodies against the von Willebrand factor cleaving protease ADAMTS13 as
the etiology of most cases of one major form of TMA, thrombotic thrombocytopenic
purpura, it permitted appropriate use of life-saving interventions based on
plasma exchange and immune suppression. A more recent factor in TMA therapeutics
was the 2011 approval by the US FDA and European EMA of eculizumab, a humanized
monoclonal antibody against complement component C5, for the treatment of
atypical hemolytic uremic syndrome, another major form of TMA. Despite these
milestones, life- and organ-threatening TMAs still occur in untreated HIV disease
and, to a much lesser extent, in those patients with suppressed viral loads.
Confusion in terms of the differential diagnosis of these TMAs also impedes use
of directed treatments. This report utilizes a case study of a young woman with
advanced AIDS who presented with a severe TMA, characterized by coma and renal
failure, to highlight the diagnostic and therapeutic challenges raised by complex
hematologic conditions occurring in the setting of HIV.
PMID- 27509236
TI - Growth of HIV-Infected Children in the Early Stage of Antiretroviral Treatment: A
Retrospective Cohort Study in China.
AB - Malnutrition and human immunodeficiency virus (HIV)-related complications are
commonly seen in HIV-infected children, and these have been shown in high
prevalent areas such as Africa. Antiviral therapy (ART) has notably controlled
disease progression, whereas it effectively reverses underweight and growth
retardation in HIV-infected children. This study was conducted to evaluate the
growth status after initiation of ART in HIV-infected children in China. A
retrospective cohort study was conducted based on the National Science and
Technology Major Project. HIV-infected children who initiated antiretroviral
treatment between January 1st, 2012 and December 31st, 2012 were followed up to
December 31st, 2014. Z-scores of height and weight were calculated by WHO Anthro
(plus). Linear mixed-effects models were used to model trajectories of weight-
and height-for-age Z-scores. Seven hundred forty-four participants enrolled in
the study, with 585 participants and 712 participants who had WAZ (weight-for-age
Z-score) and HAZ (height-for-age Z-score), respectively, before initiation of
ART. Among them, 125 (21.4%) were underweight and 301 (42.3%) were stunted. After
treatment, among the 125 underweight children, WAZ improved in 69 patients,
regained more than -2 on average. Among the 301 stunted children, HAZ improved in
123 patients, regained more than -2 on average. WAZ improved for the first 6
months by 0.052 units each month and then stabilized, whereas HAZ consistently
improved by 0.014 units each month over time. Antiretroviral treatment reversed
the adverse effects of HIV to some degree. Early diagnosis and treatment, with an
effective nutrition program, is necessary to improve malnutrition further.
PMID- 27509237
TI - Community-Based HIV and Health Testing for High-Risk Adolescents and Youth.
AB - Adolescents account for 40% of new HIV infections, and HIV testing strategies to
increase uptake of testing are needed. A community-based adolescent and youth HIV
and health testing campaign was conducted in seven slum neighborhoods of Port-au
Prince, Haiti, from December 2014 to September 2015. Community health workers
provided community sensitization and recruited 10- to 24-year-olds to test for
HIV, syphilis, gonorrhea/chlamydia, and to screen for tuberculosis (TB) and
pregnancy. HIV-infected individuals were escorted to the GHESKIO HIV clinic for
same-day enrollment in care. Among 3425 individuals eligible for testing, 3348
(98%) accepted an HIV test. HIV prevalence was 2.65% (n = 89). Median age was 19
[interquartile range (IQR) 17-20]; 73% were female. HIV prevalence was 0.6-7.4%
across slum neighborhoods. All HIV-infected individuals enrolled in care the same
day as testing; median CD4 was 529 cells/MUL [IQR 363-761]. Syphilis prevalence
was 2.60% (65/2536) and gonorrhea/chlamydia prevalence was 6.25% (96/1536). Among
168 (5%) individuals who reported TB symptoms, 7.7% (13/168) had
microbiologically confirmed disease. One hundred twenty-nine females (5% of all
females) were pregnant. This community-based testing campaign identified an
adolescent and youth population with an HIV prevalence six times higher than the
estimated national adolescent HIV prevalence (0.4%) in Haiti, including
perinatally infected adolescents. This type of community-based campaign for HIV
testing within a package of services can serve as a model for other resource-poor
settings to identify high-risk adolescents and youth, and curb the global HIV
epidemic among adolescents.
PMID- 27509238
TI - Challenges in Recruiting People Who Use Drugs for HIV-Related Biomedical
Research: Perspectives from the Field.
AB - Recruitment of people who use drugs (PWUD) for HIV-related research has been
undertaken since early in the epidemic. In early studies, recruitment was often
performed by outreach workers with familiarity with the target population, who
distributed risk reduction materials, and administered the surveys being
conducted on drug use and risk behaviors. The evolution of effective treatments
for HIV has provided opportunities for PWUD to participate in biobehavioral
studies testing the efficacy of medical treatment advances and exploring the
underlying biomedical basis for prevention and treatment efforts. Recruitment for
these studies has led to new challenges for outreach workers and institutions
conducting this research. PWUD, particularly those from race/ethnic minority
populations, have had lower rates of engagement in HIV care and have been
underrepresented in HIV/AIDS medical studies. To address these health
disparities, enhanced efforts are needed to increase their participation in
biomedical studies. This article examines the challenges identified by
experienced outreach workers in recruiting PWUD for HIV-related biomedical
studies, including individual (participant)-, institutional-, and recruiter-level
challenges, and provides recommendations for addressing them.
PMID- 27509240
TI - The brain gets its say: Hepatic encephalopathy and its evolving role in
transplant priority.
PMID- 27509239
TI - "I Have to Push Him with a Wheelbarrow to the Clinic": Community Health Workers'
Roles, Needs, and Strategies to Improve HIV Care in Rural South Africa.
AB - With a 19.2% HIV prevalence, South Africa has the largest HIV/AIDS epidemic
worldwide. Despite a recent scale-up of public sector HIV resources, including
community-based programs to expand HIV care, suboptimal rates of antiretroviral
therapy (ART) initiation and adherence persist. As community stakeholders with
basic healthcare training, community health workers (CHWs) are uniquely
positioned to provide healthcare and insight into potential strategies to improve
HIV treatment outcomes. The study goal was to qualitatively explore the self
perceived role of the CHW, unmet CHW needs, and strategies to improve HIV care in
rural KwaZulu-Natal, South Africa. Focus groups were conducted in May-August
2014, with 21 CHWs working in Msinga subdistrict. Interviews were audio-recorded,
transcribed, and translated from Zulu into English. A hybrid deductive and
inductive analytical method borrowed from grounded theory was applied to identify
emergent themes. CHWs felt they substantially contributed to HIV care provision
but were inadequately supported by the healthcare system. CHWs' recommendations
included: (1) sufficiently equipping CHWs to provide education, counseling,
social support, routine antiretroviral medication, and basic emergency care, (2)
modifying clinical practice to provide less stigmatizing, more patient-centered
care, (3) collaborating with traditional healers and church leaders to reduce
competition with ART and provide more holistic care, and (4) offsetting
socioeconomic barriers to HIV care. In conclusion, CHWs can serve as resources
when designing and implementing interventions to improve HIV care. As HIV/AIDS
policy and practice evolves in South Africa, it will be important to recognize
and formally expand CHWs' roles supporting the healthcare system.
PMID- 27509241
TI - Electromagnetic Property and Tunable Microwave Absorption of 3D Nets from Nickel
Chains at Elevated Temperature.
AB - We fabricated the nickel chains by a facile wet chemical method. The morphology
of nickel chains were tailored by adjusting the amount of PVP during the
synthesis process. Both the complex permittivity and permeability of the three
dimensional (3D) nets constructed by nickel chains present strong dependences on
temperature in the frequency range of 8.2-12.4 GHz and temperature range of 323
573 K. The peaks in imaginary component of permittivity and permeability mainly
derive from interfacial polarizations and resonances, devoting to dielectric and
magnetic loss, respectively. The effect from both dielectric and magnetism
contribute to enhancing the microwave absorption. The maximum absorption value of
the 3D nickel chain nets is approximately -50 dB at 8.8 GHz and 373 K with a
thickness of 1.8 mm, and the bandwidth less than -10 dB almost covers the whole
investigated frequency band. These are encouraging findings, which provide the
potential advantages of magnetic transition metal-based materials for microwave
absorption application at elevated temperature.
PMID- 27509242
TI - Reduced IL-7R T Cell Expression and Increased Plasma sCD127 in Late Presenting
HIV-Infected Individuals.
AB - BACKGROUND: Late presentation of HIV infection is associated with reduced chance
of optimal immune recovery after initiating combination antiretroviral therapy
(cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL
7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study
aimed to describe IL-7R and IL-7 before and after initiation of cART in late
presenting HIV-infected individuals, and the impact on immune recovery and T cell
subset distribution after initiation of cART. METHODS: A total of 100 HIV
infected individuals initiating cART were included in a prospective study.
Samples were collected at baseline and after 6, 12, and 24 months of cART.
Proportion and expression {[median fluorescence intensity (MFI)]} of IL-7R on T
cells, and plasma concentrations of soluble CD127 (sCD127) and IL-7 were
determined. RESULTS: The IL-7R expression was reduced in late presenters with CD4
cell count <200 cells per microliter compared with nonlate presenters and healthy
controls as demonstrated by lower proportion of CD127 + CD132 + T cells and lower
CD127 MFI. In contrast, plasma sCD127 was higher. These differences were partly
reversed after suppressive cART. Interestingly, the CD127 MFI on CD4 T cells was
found to be a predictor of increased thymic output after 24 months of suppressive
cART. CONCLUSIONS: Severely altered IL-7R expression was found in late
presenters, and associations between IL-7R expression and thymic output after 24
months of suppressive cART indicate an impact of a IL-7 response for the long
term de novo production from thymus.
PMID- 27509244
TI - Using CD4 Data to Estimate HIV Incidence, Prevalence, and Percent of Undiagnosed
Infections in the United States.
AB - INTRODUCTION: The incidence and prevalence of HIV infection are important
measures of HIV trends; however, they are difficult to estimate because of the
long incubation period between infection and symptom development and the relative
infrequency of HIV screening. A new method is introduced to estimate HIV
incidence, prevalence, and the number of undiagnosed infections in the United
States using data from the HIV case surveillance system and CD4 test results.
METHODS: Persons with HIV diagnosed during 2006-2013 and their CD4 test results
were used to estimate the distribution of diagnosis delay from HIV infection to
diagnosis based on a well-characterized CD4 depletion model. This distribution
was then used to estimate HIV incidence, prevalence, and the number of
undiagnosed infections. RESULTS: Applying this method, we estimated that the
annual number of new HIV infections decreased after 2007, from 48,300 (95%
confidence interval [CI]: 47,300 to 49,400) to 39,000 (95% CI: 36,600 to 41,400)
in 2013. Prevalence increased from 923,200 (95% CI: 914,500 to 931,800) in 2006
to 1,104,600 (95% CI: 1,084,300 to 1,124,900) in 2013, whereas the proportion of
undiagnosed infections decreased from 21.0% in 2006 (95% CI: 20.2% to 21.7%) to
16.4% (95% CI: 15.7% to 17.2%) in 2013. CONCLUSIONS: HIV incidence, prevalence,
and undiagnosed infections can be estimated using HIV case surveillance data and
information on first CD4 test result after diagnosis. Similar to earlier
findings, the decreases in incidence and undiagnosed infections are encouraging
but intensified efforts for HIV testing and treatment are needed to meet the
goals of the National HIV/AIDS Strategy.
PMID- 27509243
TI - Chronic HIV-1 Infection Impairs Superantigen-Induced Activation of Peripheral
CD4+CXCR5+PD-1+ Cells, With Relative Preservation of Recall Antigen-Specific
Responses.
AB - Peripheral CD4+CXCR5+PD-1+ T cells are a putative circulating counterpart to
germinal center T follicular helper (TFH) cells. They show both phenotypic and
functional similarities to TFH cells, which provide necessary help for the
differentiation of B cells to antibody-secreting plasmablasts. In this study, we
evaluated the frequency, phenotypes, and responses of peripheral TFH-like (pTFH)
cells to superantigen and recall antigen stimulation in 10 healthy and 34
chronically infected treatment-naive HIV-1+ individuals. There was no difference
in the frequency of pTFH cells between HIV+ and HIV- individuals. Surface
expression of ICOS, but not CD40L, was higher on pTFH cells at baseline in HIV+
individuals. Compared with HIV- individuals, pTFH cells from HIV+ individuals had
decreased maximal expression of ICOS and CD40L in response to in vitro
superantigen stimulation. This decreased response did not correlate with viral
control, CD4 T-cell count, duration of infection, or the degree of neutralizing
antibody breadth. Despite a decreased maximal response, pTFH responses to HIV Gag
and tetanus toxoid recall antigens were preserved.
PMID- 27509245
TI - Precursor Forms of Vitamin D Reduce HIV-1 Infection In Vitro.
AB - BACKGROUND: Although the anti-HIV-1 effects of vitamin D (VitD) have been
reported, mechanisms behind such protection remain largely unexplored. METHODS:
The effects of two precursor forms (cholecalciferol/calciol at 0.01, 1 and 100 nM
and calcidiol at 100 and 250 nM) on HIV-1 infection, immune activation, and gene
expression were analyzed in vitro in cells of Colombian and Italian healthy
donors. We quantified levels of released p24 by enzyme-linked immunosorbent
assay, of intracellular p24 and cell-surface expression of CD38 and HLA-DR by
flow cytometry, and mRNA expression of antiviral and immunoregulatory genes by
real-time reverse transcription-polymerase chain reaction. RESULTS:
Cholecalciferol decreased the frequency of HIV-1-infected p24CD4 T cells and
levels of p24 in supernatants in a dose-dependent manner. Moreover, the
CD4CD38HLA-DR and CD4CD38HLA-DR subpopulations were more susceptible to infection
but displayed the greatest cholecalciferol-induced decreases in infection rate by
an X4-tropic strain. Likewise, cholecalciferol at its highest concentration
decreased the frequency of CD38HLA-DR but not of CD38HLA-DR T-cell subsets.
Analyzing the effects of calcidiol, the main VitD source for immune cells and an
R5-tropic strain as the most frequently transmitted virus, a reduction in HIV-1
productive infection was also observed. In addition, an increase in mRNA
expression of APOBEC3G and PI3 and a reduction of TRIM22 and CCR5 expression,
this latter positively correlated with p24 levels, was noted. CONCLUSIONS: VitD
reduces HIV-1 infection in T cells possibly by inducing antiviral gene
expression, reducing the viral co-receptor CCR5 and, at least at the highest
cholecalciferol concentration, by promoting an HIV-1-restrictive CD38HLA-DR
immunophenotype.
PMID- 27509246
TI - Trends in the Marginal Cost of Male Circumcision in Rural Rakai Uganda.
AB - INTRODUCTION: Male circumcision (MC) is an effective intervention to reduce HIV
acquisition in men in Africa. We conducted a cost analysis using longitudinal
data on expenditures on services and community mobilization to estimate the
marginal cost of MC over time and understand cost drivers during scale-up.
METHODS: We used a time series with monthly records from 2008 to 2013, for a
total of 72 monthly observations, from the Rakai MC Program in Uganda.
Generalized linear models were used to estimate the marginal cost of an MC
procedure. RESULTS: The marginal cost per MC in a mobile camp was $23 (P < 0.01)
and in static facilities was $35 (P < 0.1). Major cost drivers included supplies
in mobile camps with increasing numbers of surgeries, savings due to task
shifting from physicians to clinical officers, and increased efficiency as
personnel became more experienced. CONCLUSIONS: As scale-up continues, marginal
costs may increase because of mobilization needed for less motivated late
adopters, but improved efficiency could contain costs.
PMID- 27509247
TI - Performance of the Bio-Rad Geenius HIV1/2 Supplemental Assay in Detecting
"Recent" HIV Infection and Calculating Population Incidence.
AB - OBJECTIVE: HIV seroconversion biomarkers are being used in cross-sectional
studies for HIV incidence estimation. Bio-Rad Geenius HIV-1/2 Supplemental Assay
is an immunochromatographic single-use assay that measures antibodies (Ab)
against multiple HIV-1/2 antigens. The objective of this study was to determine
whether the Geenius assay could additionally be used for recency estimation.
DESIGN: This assay was developed for HIV-1/2 confirmation; however, quantitative
data acquired give information on increasing concentration and diversity of
antibody responses over time during seroconversion. A quantitative threshold of
recent HIV infection was proposed to determine "recent" or "nonrecent" HIV
infection; performance using this cutoff was evaluated. METHODS: We tested 2500
highly characterized specimens from research subjects in the United States,
Brazil, and Africa with well-defined durations of HIV infection. Regression and
frequency estimation were used to estimate assay properties relevant to HIV
incidence measurement: mean duration of recent infection (MDRI), false-recent
rate, and assay reproducibility and robustness. RESULTS: Using the manufacturer's
proposed cutoff index of 1.5 to identify "recent" infection, the assay has an
estimated false-recent rate of 4.1% (95% CI: 2.2 to 7.0) and MDRI of 179 days
(155 to 201) in specimens from treatment-naive subjects, presenting performance
challenges similar to other incidence assays. Lower index cutoffs associated with
lower MDRI gave a lower rate of false-recent results. CONCLUSIONS: These data
suggest that with additional interpretive analysis of the band intensities using
an algorithm and cutoff, the Geenius HIV-1/2 Supplemental Assay can be used to
identify recent HIV infection in addition to confirming the presence of HIV-1 and
HIV-2 antibodies.
PMID- 27509250
TI - Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV
Infection but Not Associated With Subclinical Atherosclerosis.
AB - BACKGROUND: Cardiovascular disease contributes to excess morbidity and mortality
in HIV infection, and endothelial dysfunction may contribute to this pattern. We
aimed to determine the endothelial function in treated and untreated HIV-infected
individuals and investigate potential associations with viral replication, immune
activation, coagulation, platelet function, and subclinical atherosclerosis.
METHODS: Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction)
and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma
from two previously established cross-sectional cohorts: cohort A including 50
untreated and 50 antiretroviral therapy (ART)-treated HIV-infected individuals
with previously assessed coagulation and platelet function and cohort B including
105 HIV-infected individuals on ART and 105 uninfected controls with previously
assessed coronary artery calcium score, myocardial perfusion defects, and carotid
intima-media thickness. RESULTS: Concentrations of ADMA were higher in HIV
infected individuals compared with uninfected controls, and higher ADMA was found
in ART-treated compared with untreated HIV-infected individuals. ADMA was
associated with viral load, sCD14, D-dimer, and low CD4 T-cell count in untreated
HIV infection. Only viral load remained significant in multivariate analyses. In
ART-treated HIV-infected individuals, ADMA was not associated with coronary
artery calcium score, myocardial perfusion defects, or intima-media thickness.
CONCLUSIONS: Evidence of endothelial dysfunction was found in HIV infection and
in untreated compared with treated HIV infection. In untreated HIV infection, the
main driver of endothelial dysfunction was viral replication. Importantly, in
treated HIV infection, ADMA was not associated with subclinical atherosclerosis.
Thus, our data question the potential of ADMA as a useful biomarker of early
atherosclerosis in treated HIV infection.
PMID- 27509251
TI - Evaluation of Sexual Risk Behavior Among Study Participants in the TDF2 PrEP
Study Among Heterosexual Adults in Botswana.
AB - OBJECTIVE: Among participants of a clinical trial to test the efficacy of
tenofovir/emtricitabine in protecting heterosexual men and women living in
Botswana from HIV infection, the aim was to determine (1) if sexual risk
behavior, specifically condomless sex acts and number of sex partners, changed
over time, (2) factors associated with condomless sex acts and number of sex
partners, and (3) the effect of participant treatment arm perception on risk
behavior to address the possibility of risk compensation. METHODS: A longitudinal
modeling of rates of risk behaviors was used to determine if the rate of
condomless sex acts (#acts/person) and rate of sex partners (#partners/person)
changed over time and which factors were associated with behavior change.
RESULTS: One thousand two hundred participants were analyzed over 1 year. There
was a 25% decrease in the rate of sex partners among participants sexually active
in the last 30 days. The rate of reported condomless sex acts was greater for
males [rate ratio (RR) = 1.34; confidence interval (CI): 1.07 to 1.67] and
participants whose sexual debut in years was <=15 years of age (RR = 1.65; CI:
1.14 to 2.38) and 16-17 (RR = 1.68; CI: 1.22 to 2.31) compared with those >=20
years. Rate of reported sex partners was greater for males (RR = 3.67; CI: 2.86
to 4.71) and participants whose age at sexual debut in years was <=15 (RR = 2.92;
CI: 2.01 to 4.22) and 16-17 (RR = 2.34; CI: 1.69 to 3.24) compared with those
>=20. There was no effect of participant treatment arm perception on risk
behavior. CONCLUSIONS: Our study of preexposure prophylaxis to prevent HIV
infection found no evidence of risk compensation which may have been due to
participants' motivations to reduce their risk behaviors and risk-reduction
counseling.
PMID- 27509254
TI - Brief Report: Sexual Violence Against HIV-Positive Women in the Nyanza Region of
Kenya: Is Condom Negotiation an Instigator?
AB - For people living with HIV, exposure to sexual violence (SV) is associated with
decreased adherence to antiretroviral medication, a primary predictor of their
survival. Identification of risk factors for SV is a pressing issue in sub
Saharan Africa, where the global majority of HIV-positive women live and the
prevalence of SV against women is high. We used qualitative data to examine SV
against HIV-positive women enrolled in HIV care in Kenya. Respondents identified
husbands as perpetrators of SV in the context of women's efforts to use condoms
as directed by HIV care providers.
PMID- 27509255
TI - Highly Tunable Complementary Micro/Submicro-Nanopatterned Surfaces Combining
Block Copolymer Self-Assembly and Colloidal Lithography.
AB - Two kinds of large-area ordered and highly tunable micro/submicro-nanopatterned
surfaces in a complementary manner were successfully fabricated by elaborately
combining block copolymer self-assembly and colloidal lithography. Employing a
monolayer of polystyrene (PS) colloidal spheres assembled on top as etching mask,
polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) or polystyrene-block-poly(4
vinylpyridine) (PS-b-P4VP) micelle films were patterned into micro/submicro
patches by plasma etching, which could be further transferred into micropatterned
metal nanoarrays by subsequent metal precursor loading and a second plasma
etching. On the other hand, micro/submicro-nanopatterns in a complementary manner
were generated via preloading a metal precursor in initial micelle films before
the assembly of PS colloidal spheres on top. Both kinds of micro/submicro
nanopatterns showed good fidelity at the micro/submicroscale and nanoscale;
meanwhile, they could be flexibly tuned by the sample and processing parameters.
Significantly, when the PS colloidal sphere size was reduced to 250 nm, a high
resolution submicro-nanostructured surface with 3-5 metal nanoparticles in each
patch or a single-nanoparticle interconnected honeycomb network was achieved.
Moreover, by applying gold (Au) nanoparticles as anchoring points,
micronanopatterned Au arrays can serve as a flexible template to pattern bovine
serum albumin (BSA) molecules. This facile and cost-effective approach may
provide a novel platform for fabrication of micropatterned nanoarrays with high
tunability and controllability, which are promising in the applications of
biological and microelectronic fields.
PMID- 27509256
TI - Cell autonomous or systemic EGFR blockade alters the immune-environment in
squamous cell carcinomas.
AB - Targeting mutations and amplifications in the EGFR has been successful precision
therapy for cancers of the lung, oral cavity and gastrointestinal track. However,
a systemic immune reaction manifested by dose-limiting inflammation in the skin
and gut has been a consistent adverse effect. To address the possibility that
intra-tumoral immune changes contribute to the anti-cancer activity of EGFR
inhibition, squamous cancers were produced by syngeneic orthografts of either
EGFR null or wildtype mouse primary keratinocytes transduced with an oncogenic H
ras retrovirus. Flow cytometric, RNA and Bioplex immunoassay analyses of the
tumor immune milieu were performed. Cancers forming from keratinocytes
genetically depleted of EGFR were smaller than wildtype cancers and had fewer
infiltrating FoxP3 Treg cells, lower Foxp3 RNA and a lower percentage of CD4 PD1
positive cells indicating a tumor cell autonomous regulation of its
microenvironment. Hosts bearing wildtype cancers treated with gefitinib for 1
week showed a trend for smaller tumors. In this short term pharmacological model,
there was also a trend to reduced FoxP3 cells and FoxP3 RNA in the tumors of
treated mice as well as a substantial increase in the ratio of IL-1A/IL-1RA
transcripts. These results suggest that relatively brief systemic inhibition of
EGFR signaling alters the immune environment of the targeted cancer. Together
these data imply that an EGFR dependent Treg function supports the growth of
squamous cancers and is a target for the therapeutic activity of EGFR inhibition.
PMID- 27509257
TI - JAN Classic article: Patients' emotional reactions to hospitalization: an
exploratory study.
PMID- 27509258
TI - On the potential of phase-change adsorbents for CO2 capture by temperature swing
adsorption.
AB - We investigate the potential of a class of recently discovered metal-organic
framework materials for their use in temperature swing adsorption (TSA) processes
for CO2 capture; the particularity of the considered materials is their
reversible and temperature dependent step-shaped CO2 adsorption isotherm.
Specifically, we present a comprehensive modeling study, where the performance of
five different materials with step-shaped isotherms [McDonald et al., Nature,
2015, 519, 303] in a four step TSA cycle is assessed. The specific energy
requirement of the TSA process operated with these materials is lower than for a
commercial 13X zeolite, and a smaller temperature swing is required to reach
similar levels of CO2 purity and recovery. The effect of a step in the adsorption
isotherm is illustrated and discussed, and design criteria that lead to an
optimal and robust operation of the considered TSA cycle are identified. The
presented criteria could guide material scientists in designing novel materials
whose step position is tailored to specific CO2 separation tasks.
PMID- 27509259
TI - Loss of GFAT1 promotes epithelial-to-mesenchymal transition and predicts
unfavorable prognosis in gastric cancer.
AB - Gastric cancer remains the third leading cause of cancer-related mortality
worldwide, and invasion and metastasis of gastric cancer represent the major
reason for its poor prognosis. Glutamine: fructose-6-phosphate amidotransferase 1
(GFAT1) is the first and rate-limiting enzyme of hexosamine biosynthesis pathway
(HBP). Nevertheless, the role of GFAT1 in gastric cancer is little investigated.
In this study, we found that the expression of GFAT1 was decreased in gastric
cancer. Low expression of GFAT1 was positively associated with vessel invasion,
late T stage, lymph node metastasis, distant metastasis, advanced TNM stage and
poor prognosis in patients with gastric cancer. Furthermore, in vitro and in vivo
studies revealed that down-regulation of GFAT1 promoted epithelial-to-mesenchymal
transition (EMT) and invasive activities in gastric cancer cells through inducing
the expression of TGF-beta1. The GFAT1 expression also significantly correlated
with EMT-related factors in gastric cancer patients. Together, these findings
indicate that GFAT1 functions as a novel suppressor of EMT and tumor metastasis
in gastric cancer.
PMID- 27509260
TI - Everolimus affects vasculogenic mimicry in renal carcinoma resistant to
sunitinib.
AB - Angiogenesis is hallmark of clear cell renal cell carcinogenesis. Anti-angiogenic
therapies have been successful in improving disease outcome; however, most
patients treated with anti-angiogenic agents will eventually progress. In this
study we report that clear cell renal cell carcinoma was associated with
vasculogenic mimicry in both mice and human with tumor cells expressing
endothelial markers in the vicinity of tumor vessels. We show that vasculogenic
mimicry was efficiently targeted by sunitinib but eventually associated with
tumor resistance and a more aggressive phenotype both in vitro and in vivo. Re
challenging these resistant tumors in mice, we showed that second-line treatment
with everolimus particularly affected vasculogenic mimicry and tumor cell
differentiation compared to sorafenib and axitinib. Finally, our results
highlighted the phenotypic and genotypic changes at the tumor cell and
microenvironment levels during sunitinib response and progression and the
subsequent improvement second-line therapies bring to the current renal cell
carcinoma treatment paradigm.
PMID- 27509261
TI - Association of peripheral leukocyte telomere length and its variation with
pancreatic cancer and colorectal cancer risk in Chinese population.
AB - There is increasing evidence supporting the role of telomeres in cancer
pathogenesis. However, limited studies have investigated the association between
telomere length features and risk of pancreatic cancer and colorectal cancer
(CRC), and little was conducted in Asians. To help clarify this issue, We
measured relative peripheral leukocytes telomere length (LTL) and telomere length
variation (TLV) in a prospective study of 900 pancreatic cancer cases, 300 CRC
cases, and 900 controls. Both subjects with longer LTL (quartile 4: adjusted
OR=1.51, 95% CI: 1.14-1.99, P=0.004) and shorter LTL (quartile 1: adjusted
OR=3.12, 95% CI: 1.89-5.14, P=8.50x10-6) showed increased risk of pancreatic
cancer. A linear increased risk was detected For TLV (adjusted OR=1.60, 95% CI:
1.14-2.24, P=0.006). We also identified significant interaction for relative LTL,
TLV on pancreatic cancer risk (P interaction =0.009). Significant relationship
between shorter RTL and increased CRC risk were also detected. This findings
provide insights into telomere dynamics and highlight the complex relationship
between relative LTL, TLV and cancer risk.
PMID- 27509262
TI - Transporters affecting biochemical test results: Creatinine-drug interactions.
AB - Creatinine is eliminated by the kidneys through a combination of glomerular
filtration and active transport. Drug-induced increases in serum creatinine (SCr)
and/or reduced creatinine renal clearance are used as a marker for acute kidney
injury. However, inhibition of active transport of creatinine can result in
reversible and, therefore, benign increases in SCr levels. Herein, the
transporters involved in creatinine clearance are discussed, in addition to
limitations of using creatinine as a biomarker for kidney damage.
PMID- 27509263
TI - DNA methylation regulates gabrb2 mRNA expression: developmental variations and
disruptions in l-methionine-induced zebrafish with schizophrenia-like symptoms.
AB - Single nucleotide polymorphisms (SNPs) in the human type A gamma-aminobutyric
acid (GABA) receptor beta2 subunit gene (GABRB2) have been associated with
schizophrenia and quantitatively correlated with mRNA expression in the
postmortem brain tissue of patients with schizophrenia. l-Methionine (MET)
administration has been reported to cause a recrudescence of psychotic symptoms
in patients with schizophrenia, and similar symptoms have been generated in MET
induced mice. In this study, a zebrafish animal model was used to evaluate the
relationship between the gabrb2 mRNA expression and its promoter DNA methylation
in developmental and MET-induced schizophrenia-like zebrafish. The results
indicated developmental increases in global DNA methylation and decreases in
gabrb2 promoter methylation in zebrafish. A significant increase in gabrb2 mRNA
levels was observed after GABA was synthesized. Additionally, the MET-triggered
schizophrenia-like symptoms in adult zebrafish, involving social withdrawal and
cognitive dysfunction analyzed with social interaction and T-maze behavioral
tests, were accompanied by significantly increased DNA methylation levels in the
global genome and the gabrb2 promoter. Furthermore, the significant correlation
between gabrb2 mRNA expression and gabrb2 promoter methylation observed in the
developmental stages became non-significant in MET-triggered adult zebrafish.
These findings demonstrate that gabrb2 mRNA expression is associated with DNA
methylation varies by developmental stage and show that these epigenetic
association mechanisms are disrupted in MET-triggered adult zebrafish with
schizophrenia-like symptoms. In conclusion, these results provide plausible
epigenetic evidence of the GABAA receptor beta2 subunit involvement in the
schizophrenia-like behaviors and demonstrate the potential use of zebrafish
models in neuropsychiatric research.
PMID- 27509264
TI - Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth
Weight Preterm Infants.
AB - BACKGROUND: Induction of lung maturation by prenatal steroid treatment has become
the standard of care for pregnant women at risk for preterm birth. In addition to
the beneficial effects on lung maturation, prenatal steroids have been shown to
reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and
intraventricular hemorrhage. However, little is known about the role of
interindividual differences in corticoid sensitivity arising from polymorphisms
in the glucocorticoid receptor (GR) gene. OBJECTIVES: To assess the impact of GR
polymorphisms N363S (rs56149945), R23K (rs6190), and BclI (rs41423247) on
neonatal outcome. METHODS: The GR polymorphisms N363S, R23K, and BclI were
examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German
tertiary level neonatal units (German Neonatal Network, GNN) with respect to
neonatal outcome. RESULTS: Infants carrying the BclI genotype were at higher risk
to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per BclI allele, 95% CI:
1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational
age, mechanical ventilation, and small for gestational age status. A similar
relative risk was seen in the children (89.4%) who received antenatal
betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such
effect was detectable in infants without antenatal steroids. N363S and R23K did
not show any stable association with neonatal outcome parameters. CONCLUSION:
Except for a slightly higher risk of BPD in carriers of the GRBclI variant, the
GR gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome
parameters in this large multicenter cohort of VLBW preterm infants.
PMID- 27509265
TI - Phase transformations, microstructure formation and in vitro osteoblast response
in calcium silicate/brushite cement composites.
AB - Self-setting simple calcium silicate/brushite (B) biocements with various Ca/P
ratios were prepared by mutual mixing of both monocalcium silicate hydrate (CSH)
or beta-wollastonite (woll) powders with B and the addition of 2 wt% NaH2PO4
solution as a hardening liquid. The phase composition of the final composites and
the texture of the surface calcium phosphate/silica layer were controlled by the
starting Ca/P ratio in composites and the pH during setting. It was verified that
the presence of continuous bone-like calcium phosphate coating on the surface of
the samples was not essential for in vitro osteoblast proliferation. The
nanocrystalline calcium deficient hydroxyapatite and amorphous silica were found
as the main setting products in composite mixtures with a Ca/P ratio close to the
region of the formation of deficient hydroxyapatite-like calcium phosphates. No
CSH phase with a lower Ca/Si ratio was identified after transformation. The
results confirmed a small effect of the monocalcium silicate addition on the
compressive strength (CS) of cements up to 30 wt% (around 20-25 MPa) and a
significant rise of the value in 50 woll/B cement (65 MPa). The final setting
times of the cement composites varied between 5 and 43 min depending on the P/L
ratio and the type of monocalcium silicate phase in the cement mixture. 10CSH/B
and 50 woll/B cements with different textures but free of both the needle-like
and perpendicularly-oriented hydroxyapatite particles on the surface of the
samples had low cytotoxicity.
PMID- 27509266
TI - Incidental paranasal sinusitis on routine brain magnetic resonance scans:
association with atherosclerosis.
AB - BACKGROUND: Incidental paranasal sinusitis (IPS) is common on imaging for non
sinusitis disorders, usually without symptoms or obstructive features, and
possibly arising from periodontitis (PD). PD associations with atherosclerosis
have been widely reported. We test if IPS may also be associated with
atherosclerosis. METHODS: IPS was scored retrospectively in a random sample of
180 magnetic resonance (MR) brain scans and compared with chart review for
atherosclerosis (all subtypes), rhinosinusitis, and related factors (smoking,
asthma, and relevant surgery). IPS was scored out of 30, from all sinuses, with
maxillary sinuses weighted double volumetrically. Significant IPS (Sig IPS) was
designated as 6 or more out of 30. Bivariate logistic regression was used to test
for associations of Sig IPS to the clinical data, with multivariate analysis then
testing for potential confounders. RESULTS: A total of 173 subjects were analyzed
(7 exclusions). MR indications included suspected acute/prior stroke (22.0%). Sig
IPS found in 20 (11.6%). Positive histories for atherosclerosis were cerebral, 57
(32.9%); coronary, 48 (27.7%); and peripheral arterial disease, 14 (8.1%). IPS
>=6 was strongly associated with cerebrovascular disease (odds ratio [OR] 6.0, p
< 0.001), and less robustly to smoking (OR 2.9, p = 0.07) and rhinosinusitis (OR
2.4, p = 0.09). No associations with coronary or peripheral artery diseases were
found. After controlling for smoking and rhinosinusitis, yielding significant
subclinical sinusitis, the link of Sig IPS to cerebrovascular disease persisted
(modified OR 5.2, p = 0.002). CONCLUSION: Significant incidental sinusitis, which
is mostly subclinical sinusitis, is associated with cerebrovascular disease but
not other atheroscleroses. This suggests possible common causation of both by PD.
PMID- 27509267
TI - Expanding on Successful Concepts, Models, and Organization.
PMID- 27509268
TI - Etiology, seasonality, and clinical characteristics of respiratory viruses in
children with respiratory tract infections in Eastern India (Bhubaneswar,
Odisha).
AB - Acute respiratory tract infections (ARTIs) are a leading cause of morbidity and
mortality in young children in low and middle income countries. To analyse the
overall burden of respiratory viruses responsible for ARTIs in paediatrics
population in eastern India, this study was performed. Clinical information,
demographic information and nasal/oral swabs were collected from 332 paediatric
patients (aged from 1 month to 12 years old) with the symptoms of ARTI, enrolled
from the outpatient department from Nov 2012 to Oct 2014. Multiplex PCR was
performed to detect eight respiratory viral pathogens. Seasonal, as well as age
wise prevalence of respiratory viruses was analysed. Of these 332 cases, 32.53%
(108/332) were positive for at least one pathogen. Human rhinovirus (HRV) was the
most frequently detected pathogen (24.7%, 82/332) followed by respiratory
syncytial virus (RSV) (4.22%, 14/332), PIV (2.11%, 7/332), and hMPV (2.11%,
7/332). Single infection was detected in 92.6% (100/108) of positive cases.
Respiratory virus infections showed seasonal variation, with peaks during the
rainy season followed by winter season, and were most common in patients under 1
year of age. Phylogenetic analysis of HMPV positive samples confirmed the
circulation of A2 subgroup in the study area. The present study is first of its
kind and adds to our knowledge of the epidemiological characteristics of these
common respiratory viruses among patients with ARTIs in the study area. J. Med.
Virol. 89:553-558, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27509270
TI - Influence of Mountaineers' Body Mass Index and Age on the Summiting Success of
Mt. Kilimanjaro (5895m) in Tanzania.
PMID- 27509271
TI - Effects of 5-O-Ribosylation of Aminoglycosides on Antimicrobial Activity and
Selective Perturbation of Bacterial Translation.
AB - We studied six pairs of aminoglycosides and their corresponding ribosylated
derivatives synthesized by attaching a beta-O-linked ribofuranose to the 5-OH of
the deoxystreptamine ring of the parent pseudo-oligosaccharide antibiotic.
Ribosylation of the 4,6-disubstituted 2-deoxystreptamine aminoglycoside kanamycin
B led to improved selectivity for inhibition of prokaryotic relative to cytosolic
eukaryotic in vitro translation. For the pseudodisaccharide aminoglycoside
scaffolds neamine and nebramine, ribosylated derivatives were both more potent
antimicrobials and more selective to inhibition of prokaryotic translation. On
the basis of the results of this study, we suggest that modification of the 5-OH
position of the streptamine ring of other natural or semisynthetic
pseudodisaccharide aminoglycoside scaffolds containing an equatorial amine at the
2' sugar position with a beta-O-linked ribofuranose is a promising avenue for the
development of novel aminoglycoside antibiotics with improved efficacy and
reduced toxicity.
PMID- 27509273
TI - AJPH Global News.
PMID- 27509272
TI - The Real World: Six Strangers Connecting AJPH to the Next Generation.
PMID- 27509274
TI - 120 000 Nurses Who Shook Public Health.
PMID- 27509275
TI - APHA Voices From the Nurses' Health Study.
PMID- 27509276
TI - A Public Health of Consequence: Review of the September 2016 Issue of AJPH.
PMID- 27509277
TI - The Nurses' Health Study and the Australian Longitudinal Study on Women's Health:
Providing Infrastructure for Public Health Research.
PMID- 27509278
TI - Long-Term Cohort Studies in Brazil: On the Tracks of the Nurses' Health Study and
Beyond.
PMID- 27509279
TI - Large Cohorts: Toward Routine Databases for Public Health Science.
PMID- 27509280
TI - How the Nurses' Health Study Helped Americans Take the Trans Fat Out.
PMID- 27509281
TI - Preparing Students to Engage in Public Health Research of Consequence.
PMID- 27509282
TI - Evaluating Public Health Interventions: 4. The Nurses' Health Study and Methods
for Eliminating Bias Attributable to Measurement Error and Misclassification.
AB - The Nurses' Health Study and many other large longitudinal cohorts around the
world use the food frequency questionnaire to assess dietary intake over time,
and to relate diet to health. Controversies concerning this questionnaire's
ability to adequately measure diet have led to a flurry of methods for evaluating
the magnitude of measurement error and misclassification in exposure assessment,
and for correcting the point and interval estimates of effect on the basis of
these assessment methods for this error. Nurses' Health Study investigators have
been in the forefront of these developments and their applications, although
hundreds of other investigators have also used them. This commentary provides an
overview of the methods and their uses, and concludes with remarks on their
potential applications in the evaluation of public health interventions.
PMID- 27509285
TI - Ebola "Ring" Vaccine Trial Was Ethically Innovative.
PMID- 27509286
TI - Ploubidis et al. Respond.
PMID- 27509287
TI - Do Men Really Benefit More From Marriage Than Women?
PMID- 27509288
TI - A Strategic Approach to Eliminating Sexual Orientation-Related Health
Disparities.
PMID- 27509289
TI - Max et al. Respond.
PMID- 27509291
TI - Pre-Implementation Strategies to Adapt and Implement a Veteran Peer Coaching
Intervention to Improve Mental Health Treatment Engagement Among Rural Veterans.
AB - PURPOSE: Telephone motivational coaching has been shown to increase urban veteran
mental health treatment initiation. However, no studies have tested telephone
motivational coaching delivered by veteran peers to facilitate mental health
treatment initiation and engagement. This study describes pre-implementation
strategies with 8 Veterans Affairs (VA) community-based outpatient clinics in the
West and Mid-South United States to adapt and implement a multisite pragmatic
randomized controlled trial of telephone peer motivational coaching for rural
veterans. METHODS: We used 2 pre-implementation strategies, Formative Evaluation
(FE) research and Evidence-Based Quality Improvement (EBQI) meetings to adapt the
intervention to stakeholders' needs and cultural contexts. FE data were
qualitative, semi-structured interviews with rural veterans and VA clinic staff.
Results were rapidly analyzed and presented to stakeholders during EBQI meetings
to optimize the intervention implementation. FINDINGS: FE research results showed
that VA clinic providers felt overwhelmed by veterans' mental health needs and
acknowledged limited mental health services at VA clinics. Rural veteran
interviews indicated geographical, logistical, and cultural barriers to VA mental
health treatment initiation and a preference for self-care to cope with mental
health symptoms. EBQI meetings resulted in several intervention adaptations,
including veteran study recruitment, peer veteran coach training, and an expanded
definition of mental health care outcomes. CONCLUSIONS: As the VA moves to
cultivate community partnerships in order to personalize and expand access to
care for rural veterans, pre-implementation processes with engaged stakeholders,
such as those described here, can help guide other researchers and clinicians to
achieve proactive and veteran-centered health care services.
PMID- 27509292
TI - Cu-Catalyzed Deoxygenative C2-Sulfonylation Reaction of Quinoline N-Oxides with
Sodium Sulfinate.
AB - An unexpected Cu-catalyzed deoxygenative C2-sulfonylation reaction of quinoline N
oxides in the presence of radical initiator K2S2O8 was developed that used sodium
sulfinate as a sulfonyl coupling partner. The mechanism studies indicate that the
reaction proceeds via Minisci-like radical coupling step to give sulfonylated
quinoline with good chemical yields.
PMID- 27509293
TI - Effects of nasal drug delivery device and its orientation on sprayed particle
deposition in a realistic human nasal cavity.
AB - In this study, the effects of nasal drug delivery device and the spray nozzle
orientation on sprayed droplets deposition in a realistic human nasal cavity were
numerically studied. Prior to performing the numerical investigation, an in-house
designed automated actuation system representing mean adults actuation force was
developed to produce realistic spray plume. Then, the spray plume development was
filmed by high speed photography system, and spray characteristics such as spray
cone angle, break-up length, and average droplet velocity were obtained through
off-line image analysis. Continuing studies utilizing those experimental data as
boundary conditions were applied in the following numerical spray simulations
using a commercially available nasal spray device, which was inserted into a
realistic adult nasal passage with external facial features. Through varying the
particle releasing direction, the deposition fractions of selected particle sizes
on the main nasal passage for targeted drug delivery were compared. The results
demonstrated that the middle spray direction showed superior spray efficiency
compared with upper or lower directions, and the 10um agents were the most
suitable particle size as the majority of sprayed agents can be delivered to the
targeted area, the main passage. This study elaborates a comprehensive approach
to better understand nasal spray mechanism and evaluate its performance for
existing nasal delivery practices. Results of this study can assist the
pharmaceutical industry to improve the current design of nasal drug delivery
device and ultimately benefit more patients through optimized medications
delivery.
PMID- 27509294
TI - Meniere's Disease: Molecular Analysis of Aquaporins 2, 3 and Potassium Channel
KCNE1 Genes in Brazilian Patients.
AB - OBJECTIVES: Meniere's disease (MD) is a complex disease of unknown etiology
characterized by a symptomatic tetrad of vertigo, hearing loss, tinnitus, and
aural fullness. In addition to factors related to homeostasis of the inner ear,
genetic factors have been implicated in its pathophysiology, including genes
related to the transport of water and ionic composition maintenance of the
endolymph, such as the aquaporin genes AQP2 and AQP3, and the potassium channel
gene KCNE1. The aim of this study was to identify polymorphisms of these genes
and determine their association with clinical characteristics of patients with
MD. DESIGN: A case-control genetic association study was carried out, including
30 patients with definite Meniere's disease and 30 healthy controls. The coding
regions of the target genes were amplified from blood samples by polymerase chain
reaction (PCR), followed by direct sequencing. The associations of polymorphisms
with clinical characteristics were analyzed with logistic regression. RESULTS:
Five polymorphisms were identified: rs426496 in AQP2; rs591810 in AQP3; and
rs1805127, rs1805128, and rs17173510 in KCNE1. After adjustment, rs426496 was
significantly associated with tinnitus during the initial crisis and with altered
electronystagmography, and rs1805127 was significantly associated with
nephropathy. CONCLUSIONS: The genetic variant rs426496 in AQP2; rs591810 in AQP3
and rs1805127, rs1805128, and rs17173510, in KCNE1 were found in patients with
Meniere's disease. The polymorphism rs426496, in AQP2, is associated with
tinnitus at the onset of Meniere's disease and altered electronystagmography. In
addition, rs1805127, in KCNE1, is associated with the presence of nephropathy.
PMID- 27509295
TI - Autonomous Optimization of Targeted Stimulation of Neuronal Networks.
AB - Driven by clinical needs and progress in neurotechnology, targeted interaction
with neuronal networks is of increasing importance. Yet, the dynamics of
interaction between intrinsic ongoing activity in neuronal networks and their
response to stimulation is unknown. Nonetheless, electrical stimulation of the
brain is increasingly explored as a therapeutic strategy and as a means to
artificially inject information into neural circuits. Strategies using regular or
event-triggered fixed stimuli discount the influence of ongoing neuronal activity
on the stimulation outcome and are therefore not optimal to induce specific
responses reliably. Yet, without suitable mechanistic models, it is hardly
possible to optimize such interactions, in particular when desired response
features are network-dependent and are initially unknown. In this proof-of
principle study, we present an experimental paradigm using reinforcement-learning
(RL) to optimize stimulus settings autonomously and evaluate the learned control
strategy using phenomenological models. We asked how to (1) capture the
interaction of ongoing network activity, electrical stimulation and evoked
responses in a quantifiable 'state' to formulate a well-posed control problem,
(2) find the optimal state for stimulation, and (3) evaluate the quality of the
solution found. Electrical stimulation of generic neuronal networks grown from
rat cortical tissue in vitro evoked bursts of action potentials (responses). We
show that the dynamic interplay of their magnitudes and the probability to be
intercepted by spontaneous events defines a trade-off scenario with a network
specific unique optimal latency maximizing stimulus efficacy. An RL controller
was set to find this optimum autonomously. Across networks, stimulation efficacy
increased in 90% of the sessions after learning and learned latencies strongly
agreed with those predicted from open-loop experiments. Our results show that
autonomous techniques can exploit quantitative relationships underlying activity
response interaction in biological neuronal networks to choose optimal actions.
Simple phenomenological models can be useful to validate the quality of the
resulting controllers.
PMID- 27509296
TI - Three-Dimensional Distribution of Phospholipids in Gram Negative Bacteria.
AB - Exploration of the molecular structure of the bacterial cell envelope informs our
understanding of its role in bacterial growth. This is crucial for research into
both inhibiting and promoting bacterial growth as well as fundamental studies of
cell cycle control. The spatial arrangement of the lipids in the cell envelope of
Gram negative bacteria in particular has attracted considerable research
attention in recent years. In this mini-review, we explore advances in
understanding the spatial distribution of lipids in the model Gram negative
prokaryote Escherichia coli. This includes the distribution of lipids in three
dimensions, (a) lateral distribution within a monolayer, (b) asymmetry between
bilayers and monolayers, and (c) distribution as a function of progress through
membrane division (temporal shifts). We conclude that lipid distribution in E.
coli and probably all bacteria is dynamic despite a narrow lipid profile and that
the biophysical properties of the membrane are inhomogeneous as a result.
Finally, we suggest that further work in this field may indicate how lipid
distribution is controlled and what this means for bacterial growth and
metabolism and even cell cycle control.
PMID- 27509297
TI - Women's Careers in Biomedical Sciences: Implications for the Economy, Scientific
Discovery, and Women's Health.
AB - While women have been well represented in medical school and biomedical doctoral
degree programs, they do not comprise half of academic medicine faculty
positions. Furthermore, there is a significant paucity of women in academic
medicine leadership positions, as evidenced by the fact that only 16% of dean
positions at United States Medical schools are filled by women. In this
commentary, the authors review the state of women in academic medicine and argue
that increased representation of women in the academic workforce will lead to
economic gains, increased scientific discovery, and improvements to women's
health.
PMID- 27509298
TI - Occlusion of Sulfate-Based Diblock Copolymer Nanoparticles within Calcite: Effect
of Varying the Surface Density of Anionic Stabilizer Chains.
AB - Polymerization-induced self-assembly (PISA) offers a highly versatile and
efficient route to a wide range of organic nanoparticles. In this article, we
demonstrate for the first time that poly(ammonium 2-sulfatoethyl methacrylate)
poly(benzyl methacrylate) [PSEM-PBzMA] diblock copolymer nanoparticles can be
prepared with either a high or low PSEM stabilizer surface density using either
RAFT dispersion polymerization in a 2:1 v/v ethanol/water mixture or RAFT aqueous
emulsion polymerization, respectively. We then use these model nanoparticles to
gain new insight into a key topic in materials chemistry: the occlusion of
organic additives into inorganic crystals. Substantial differences are observed
for the extent of occlusion of these two types of anionic nanoparticles into
calcite (CaCO3), which serves as a suitable model host crystal. A low PSEM
stabilizer surface density leads to uniform nanoparticle occlusion within calcite
at up to 7.5% w/w (16% v/v), while minimal occlusion occurs when using
nanoparticles with a high PSEM stabilizer surface density. This counter-intuitive
observation suggests that an optimum anionic surface density is required for
efficient occlusion, which provides a hitherto unexpected design rule for the
incorporation of nanoparticles within crystals.
PMID- 27509299
TI - Salt Taste Enhancing l-Arginyl Dipeptides from Casein and Lysozyme Released by
Peptidases of Basidiomycota.
AB - Some l-arginyl dipeptides were recently identified as salt taste enhancers, thus
opening the possibility to reduce dietary sodium uptake without compromising
palatability. A screening of 15 basidiomycete fungi resulted in the
identification of 5 species secreting a high peptidolytic activity (>3 kAU/mL;
azocasein assay). PFP-LC-MS/MS and HILIC-MS/MS confirmed that l-arginyl
dipeptides were liberated when casein or lysozyme served as substrate. Much
higher yields of dipeptides (42-75 MUmol/g substrate) were released from lysozyme
than from casein. The lysozyme hydrolysate generated by the complex set of
peptidases of Trametes versicolor showed the highest l-arginyl dipeptide yields
and a significant salt taste enhancing effect in a model cheese matrix and in a
curd cheese. With a broad spectrum of novel specific and nonspecific peptidases
active in the slightly acidic pH range, T. versicolor might be a suitable enzyme
source for low-salt dairy products.
PMID- 27509300
TI - Comparative Developmental Toxicity and Stress Protein Responses of Dimethyl
Sulfoxide to Rare Minnow and Zebrafish Embryos/Larvae.
AB - Dimethyl sulfoxide (DMSO), a widely used carrier solvent, can be toxic to test
organisms and has species-specific sensitivity. In this study, the developmental
toxicity and stress protein responses of DMSO to rare minnow (Gobiocypris rarus)
and zebrafish (Danio rerio) with two tests were compared in the early life stage.
In the first test, fertilized eggs were exposed to 0%, 0.0001%, 0.001%, 0.01%,
0.1%, 1.0%, 1.5%, and 2.0% v/v of DMSO until 3 days post hatching. In the second
test, larvae from 0 to 8 d were exposed to 2% DMSO until 4 days. Our results
showed that DMSO was toxic to rare minnow and zebrafish on multiple indexes, and
the no-observed-effect concentrations of DMSO in both species were 1.0% and
0.001% for developmental toxicity analysis and stress protein analysis,
respectively. Furthermore, rare minnow larvae were more sensitive than zebrafish
to DMSO for spinal malformation. The sensitive period for induction of spinal
malformation by DMSO was 0-7 d after hatch (dah) for rare minnow and 0-4 dah for
zebrafish. Together, these results will provide support to the use of DMSO in
ecotoxicological studies using rare minnow and will contribute to a better
understanding of the toxicity of DMSO.
PMID- 27509301
TI - Prediction of Estrogenic Bioactivity of Environmental Chemical Metabolites.
AB - The US Environmental Protection Agency's (EPA) Endocrine Disruptor Screening
Program (EDSP) is using in vitro data generated from ToxCast/Tox21 high
throughput screening assays to assess the endocrine activity of environmental
chemicals. Considering that in vitro assays may have limited metabolic capacity,
inactive chemicals that are biotransformed into metabolites with endocrine
bioactivity may be missed for further screening and testing. Therefore, there is
a value in developing novel approaches to account for metabolism and endocrine
activity of both parent chemicals and their associated metabolites. We used
commercially available software to predict metabolites of 50 parent compounds,
out of which 38 chemicals are known to have estrogenic metabolites, and 12
compounds and their metabolites are negative for estrogenic activity. Three ER
QSAR models were used to determine potential estrogen bioactivity of the parent
compounds and predicted metabolites, the outputs of the models were averaged, and
the chemicals were then ranked based on the total estrogenicity of the parent
chemical and metabolites. The metabolite prediction software correctly identified
known estrogenic metabolites for 26 out of 27 parent chemicals with associated
metabolite data, and 39 out of 46 estrogenic metabolites were predicted as
potential biotransformation products derived from the parent chemical. The QSAR
models estimated stronger estrogenic activity for the majority of the known
estrogenic metabolites compared to their parent chemicals. Finally, the three
models identified a similar set of parent compounds as top ranked chemicals based
on the estrogenicity of putative metabolites. This proposed in silico approach is
an inexpensive and rapid strategy for the detection of chemicals with estrogenic
metabolites and may reduce potential false negative results from in vitro assays.
PMID- 27509302
TI - A Unified Picture of S* in Carotenoids.
AB - In pi-conjugated chain molecules such as carotenoids, coupling between electronic
and vibrational degrees of freedom is of central importance. It governs both
dynamic and static properties, such as the time scales of excited state
relaxation as well as absorption spectra. In this work, we treat vibronic
dynamics in carotenoids on four electronic states (|S0?, |S1?, |S2?, and |Sn?) in
a physically rigorous framework. This model explains all features previously
associated with the intensely debated S* state. Besides successfully fitting
transient absorption data of a zeaxanthin homologue, this model also accounts for
previous results from global target analysis and chain length-dependent studies.
Additionally, we are able to incorporate findings from pump-deplete-probe
experiments, which were incompatible to any pre-existing model. Thus, we present
the first comprehensive and unified interpretation of S*-related features,
explaining them by vibronic transitions on either S1, S0, or both, depending on
the chain length of the investigated carotenoid.
PMID- 27509303
TI - Functional engineered human cardiac patches prepared from nature's platform
improve heart function after acute myocardial infarction.
AB - With the advent of induced pluripotent stem cells and directed differentiation
techniques, it is now feasible to derive individual-specific cardiac cells for
human heart tissue engineering. Here we report the generation of functional
engineered human cardiac patches using human induced pluripotent stem cells
derived cardiac cells and decellularized natural heart ECM as scaffolds. The
engineered human cardiac patches can be tailored to any desired size and shape
and exhibited normal contractile and electrical physiology in vitro. Further,
when patching on the infarct area, these patches improved heart function of rats
with acute myocardial infarction in vivo. These engineered human cardiac patches
can be of great value for normal and disease-specific heart tissue engineering,
drug screening, and meet the demands for individual-specific heart tissues for
personalized regenerative therapy of myocardial damages in the future.
PMID- 27509304
TI - Novel surface-enhanced Raman scattering-based assays for ultra-sensitive
detection of human pluripotent stem cells.
AB - Human pluripotent stem cells (hPSCs) are a promising cell source for regenerative
medicine, but their derivatives need to be rigorously evaluated for residual stem
cells to prevent teratoma formation. Here, we report the development of novel
surface-enhanced Raman scattering (SERS)-based assays that can detect trace
numbers of undifferentiated hPSCs in mixed cell populations in a highly specific,
ultra-sensitive, and time-efficient manner. By targeting stem cell surface
markers SSEA-5 and TRA-1-60 individually or simultaneously, these SERS assays
were able to identify as few as 1 stem cell in 10(6) cells, a sensitivity
(0.0001%) which was ~2000 to 15,000-fold higher than that of flow cytometry
assays. Using the SERS assay, we demonstrate that the aggregation of hPSC-based
cardiomyocyte differentiation cultures into 3D spheres significantly reduced SSEA
5(+) and TRA-1-60(+) cells compared with parallel 2D cultures. Thus, SERS may
provide a powerful new technology for quality control of hPSC-derived products
for preclinical and clinical applications.
PMID- 27509305
TI - Frequency, predictors, and outcomes of urine drug testing among patients with
advanced cancer on chronic opioid therapy at an outpatient supportive care
clinic.
AB - BACKGROUND: Data are limited on the use and outcomes of urine drug tests (UDTs)
among patients with advanced cancer. The main objective of this study was to
determine the factors associated with UDT ordering and results in outpatients
with advanced cancer. METHODS: A retrospective chart review was conducted of 1058
patients who attended an outpatient supportive care clinic from March 2014 to
November 2015. Sixty-one patients who were receiving chronic opioid therapy and
underwent UDTs were identified. A control group of 120 patients who did not
undergo UDTs was selected for comparison. RESULTS: Sixty-one of 1058 patients
(6%) underwent UDTs, and 33 of 61 patients (54%) had abnormal results.
Multivariate analysis indicated that the odds ratio for UDT ordering was 3.9 in
patients who had positive Cut Down, Annoyed, Guilty, and Eye Opener (CAGE)
questionnaire results (P = .002), 4.41 in patients aged < 45 years (P < .001),
5.58 in patients who had moderate-to-severe pain (Edmonton Symptom Assessment
Scale pain scores >=4; P < .001), 0.27 in patients with advanced-stage cancer, (P
= .008), and 0.25 in patients who had moderate-to-severe fatigue (P = .001).
Among 52 abnormal UDT results in 33 patients, the most common opioid findings
were prescribed opioids absent in urine (14 of 52 tests; 27%) and unprescribed
opioids in urine (13 of 52 tests; 25%). CONCLUSIONS: UDTs were used infrequently
among outpatients with advanced cancer who were receiving chronic opioid therapy.
Younger age, positive CAGE questionnaire results, early stage cancer or no
evidence of disease status, higher pain intensity, and lower fatigue scores were
significant predictors of UDT ordering. More than 50% of UDT results were
abnormal. More research is necessary to better characterize aberrant opioid use
in patients with advanced cancer. Cancer 2016;122:3732-9. (c) 2016 American
Cancer Society.
PMID- 27509306
TI - Human dental pulp stem cells transplantation combined with treadmill training in
rats after traumatic spinal cord injury.
AB - Spinal cord injury (SCI) is a disabling condition resulting in deficits of
sensory and motor functions, and has no effective treatment. Considering that
protocols with stem cell transplantation and treadmill training have shown
promising results, the present study evaluated the effectiveness of stem cells
from human exfoliated deciduous teeth (SHEDs) transplantation combined with
treadmill training in rats with experimental spinal cord injury. Fifty-four
Wistar rats were spinalized using NYU impactor. The rats were randomly
distributed into 5 groups: Sham (laminectomy with no SCI, n=10); SCI (laminectomy
followed by SCI, n=12); SHEDs (SCI treated with SHEDs, n=11); TT (SCI treated
with treadmill training, n=11); SHEDs+TT (SCI treated with SHEDs and treadmill
training; n=10). Treatment with SHEDs alone or in combination with treadmill
training promoted functional recovery, reaching scores of 15 and 14,
respectively, in the BBB scale, being different from the SCI group, which reached
11. SHEDs treatment was able to reduce the cystic cavity area and glial scar,
increase neurofilament. Treadmill training alone had no functional effectiveness
or tissue effects. In a second experiment, the SHEDs transplantation reduced the
TNF-alpha levels in the cord tissue measured 6 h after the injury. Contrary to
our hypothesis, treadmill training either alone or in combination, caused no
functional improvement. However, SHEDs showed to be neuroprotective, by the
reduction of TNF-alpha levels, the cystic cavity and the glial scar associated
with the improvement of motor function after SCI. These results provide evidence
that grafted SHEDs might be an effective therapy to spinal cord lesions, with
possible anti-inflammatory action.
PMID- 27509307
TI - Galunisertib (LY2157299), a transforming growth factor-beta receptor I kinase
inhibitor, attenuates acute pancreatitis in rats.
AB - Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-beta receptor
I (TGF-betaRI), is the only known TGF-beta pathway inhibitor. In the present
study, we investigated the effect of galunisertib on taurocholate (TAC)-induced
acute pancreatitis (AP) in rats, and the role of TGF-beta and NF-kappaB signaling
pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague
Dawley male rats (n=30). The rats (220+/-50 g) were administered galunisertib
intragastrically [75 mg.kg-1.day-1 for 2 days (0 and 24 h)]. Serum IL-1beta, IL
6, TNF-alpha, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were
measured by ELISA. NF-kappaB activity was detected by electrophoretic mobility
shift assay (EMSA); NF-kappaBp65 and TGF-beta1 proteins, as well as TGF-betaRI
and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was
detected by TUNEL assay. H&E staining was used to evaluate the histopathological
alterations of the pancreas. Galunisertib treatment attenuated the severity of AP
and decreased the pancreatic histological score. In addition, number of apoptotic
cells were significantly increased in the galunisertib-treated group (16.38+/
2.26) than in the AP group (8.14+/-1.27) and sham-operated group (1.82+/-0.73;
P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of
TGF-betaRI and p-Smad2/3 and inhibited NF-kappaB activation and p65 translocation
compared with the sham-operated group. Furthermore, serum IL-1beta, IL-6, TNF
alpha, AMY and LIP levels and tissue MPO activity were significantly decreased in
the galunisertib-treated group. Our data demonstrate that galunisertib attenuates
the severity of TAC-induced experimental AP in rats by inducing apoptosis in the
pancreas, inhibiting the activation of TGF-beta signals and NF-kappaB as well as
the secretion of pro-inflammatory cytokines.
PMID- 27509308
TI - The effect on clinical parameters of periodontal inflammation following non
surgical periodontal therapy with ultrasonics and chemotherapeutic cooling
solutions: a systematic review.
AB - AIM: To establish the added effect of a chemotherapeutic cooling solution in an
ultrasonic device on clinical parameters of periodontal inflammation following
non-surgical periodontal therapy. METHODS: The MEDLINE-PubMed, Cochrane-CENTRAL,
and the EMBASE databases were searched. Probing pocket depth (PPD) and clinical
attachment level (CAL) and their changes were selected as outcome variables.
Subgroup analyses were performed according to the following active ingredients:
essential oils (EO), povidone-iodine (PVP), and chlorhexidine (CHX). RESULTS:
Screening of 100 unique papers resulted in 14 eligible publications, including 16
comparisons. The meta-analysis (MA) showed that when the ultrasonic cooling
solution had adjuvant chemotherapeutic properties, the difference of means
(DiffM) for end value PPD-0.12 (95% CI: -0.42; 0.18) and for CAL the DiffM+-0.13
(95% CI: -0.39; 0.14). None of these were statistically significant, and the
findings were supported by the overall descriptive analysis. Subgroup analysis
only revealed a small effect for PVP on the difference (DiffM = -0.23, 95% CI:
0.43; -0.02) with respect to CAL (p = 0.03). CONCLUSIONS: The collective evidence
indicates that overall, no additional effects were observed. There is a "very
weak" recommendation based on the sub-analysis showing that in conjunction with
PVP, a very small gain in CAL may be expected. For the use of CHX or EO, the
added effect can be considered to be "zero." Therefore, the strength and
direction of the recommendation emerging from this review is against their use.
PMID- 27509309
TI - Water and solute transport in agricultural soils predicted by volumetric clay and
silt contents.
AB - Solute transport through the soil matrix is non-uniform and greatly affected by
soil texture, soil structure, and macropore networks. Attempts have been made in
previous studies to use infiltration experiments to identify the degree of
preferential flow, but these attempts have often been based on small datasets or
data collected from literature with differing initial and boundary conditions.
This study examined the relationship between tracer breakthrough characteristics,
soil hydraulic properties, and basic soil properties. From six agricultural
fields in Denmark, 193 intact surface soil columns 20cm in height and 20cm in
diameter were collected. The soils exhibited a wide range in texture, with clay
and organic carbon (OC) contents ranging from 0.03 to 0.41 and 0.01 to 0.08kgkg(
1), respectively. All experiments were carried out under the same initial and
boundary conditions using tritium as a conservative tracer. The breakthrough
characteristics ranged from being near normally distributed to gradually skewed
to the right along with an increase in the content of the mineral fines
(particles <=50MUm). The results showed that the mineral fines content was
strongly correlated to functional soil structure and the derived tracer
breakthrough curves (BTCs), whereas the OC content appeared less important for
the shape of the BTC. Organic carbon was believed to support the stability of the
soil structure rather than the actual formation of macropores causing
preferential flow. The arrival times of 5% and up to 50% of the tracer mass were
found to be strongly correlated with volumetric fines content. Predicted tracer
concentration breakthrough points as a function of time up to 50% of applied
tracer mass could be well fitted to an analytical solution to the classical
advection-dispersion equation. Both cumulative tracer mass and concentration as a
function of time were well predicted from the simple inputs of bulk density, clay
and silt contents, and applied tracer mass. The new concept seems promising as a
platform towards more accurate proxy functions for dissolved contaminant
transport in intact soil.
PMID- 27509310
TI - Alignment of Red Poly[dodecadyin-1,12-diol-bis(4-butoxycarbonyl-methyl-urethane)]
in Couette Flow.
AB - The flow-induced alignment of red poly[dodecadyin-1,12-diol-bis(4-butoxycarbonyl
methyl-urethane)] (poly-4BCMU) in chloroform/toluene solution is reported.
Absorption spectra have been measured over a range of shear rates in an optically
transparent quartz Couette cell. The measured spectra show that the poly-4BCMU
structure stays the same in flow, while the measured absorbance anisotropy is
attributed to the flow-induced particle alignment in the red form poly-4BCMU
solutions. A limiting orientation at shear rates >50 s(-1) is observed. Numerical
simulations show that the spectral changes are consistent with the rodlike poly
4BCMU particle having an aspect ratio of 2.9. The dichroic ratio of 1.9
interpreted from the data indicates that the individual poly-4BCMU chains do not
aggregate amorphously in the rodlike conformation, rather they show a preferred
orientation along the long axis of the prolate aggregates.
PMID- 27509311
TI - Site Redistribution, Partial Frozen-in Defect Chemistry, and Electrical
Properties of Ba1-x(Zr,Pr)O3-delta.
AB - Changes in nominal composition of the perovskite (ABO3) solid solution Ba1
x(Zr,Pr)O3-delta and adjusted firing conditions at very high temperatures were
used to induce structural changes involving site redistribution and frozen-in
point defects, as revealed by Raman and photoluminescence spectroscopies.
Complementary magnetic measurements allowed quantification of the reduced content
of Pr. Weak dependence of oxygen stoichiometry with temperature was obtained by
coulometric titration at temperatures below 1000 degrees C, consistent with a
somewhat complex partial frozen-in defect chemistry. Electrical conductivity
measurements combined with transport number and Seebeck coefficient measurements
showed prevailing electronic transport and also indicated trends expected for
partial frozen-in conditions. Nominal Ba deficiency and controlled firing at very
high temperatures allows adjustment of structure and partial frozen-in defect
chemistry, opening the way to engineer relevant properties for high-temperature
electrochemical applications.
PMID- 27509312
TI - Pharmacological investigations of a yohimbine-impulsivity interaction in rats.
AB - Both impulsivity and stress are risk factors for substance abuse, but it is not
clear how these two processes interact to alter susceptibility for the disorder.
The aim of this project was to examine the pharmacology of a stress-impulsivity
interaction in rats. To do so, we tested the effects of yohimbine on impulsive
action and then assessed whether behavioural changes could be reduced by
antagonists at different receptor subtypes. Male Long-Evans rats were injected
with various doses of yohimbine (0-5.0 mg/kg) before testing in the response
inhibition task. In subsequent experiments, yohimbine (2.5 mg/kg) was injected
following pretreatment with the following receptor antagonists: corticotropin
releasing factor receptor 1, antalarmin (0-20 mg/kg); glucocorticoid,
mifepristone (0-30 mg/kg); noradrenergic (NA) alpha1, prazosin (0-2 mg/kg); NA
alpha2, guanfacine (0-0.5 mg/kg); NA beta2, propranolol (0.5-2.0 mg/kg); dopamine
D1/5, SCH 39166 (0-0.0625 mg/kg); MU opioid, naloxone (0-2 mg/kg); or 5-HT2A,
M100907 (0.005-0.05 mg/kg). In all experiments, impulsive action was measured as
increased premature responding. Yohimbine dose dependently increased impulsive
action, but the effect was not reversed by antagonist pretreatment. None of the
drugs altered any other behavioural measure. We conclude that stress-impulsivity
interactions are likely mediated by a synergy of multiple neurotransmitter
systems.
PMID- 27509313
TI - Bilobalide alleviates depression-like behavior and cognitive deficit induced by
chronic unpredictable mild stress in mice.
AB - Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful
neuroprotection and stress-alleviating properties. However, whether BB exerts a
positive effect on depression and cognitive deficit induced by chronic stress is
not known. The present study was designed to investigate the influence of BB on
depression and cognitive impairments induced by chronic unpredictable mild stress
(CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice
were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We
replicated the finding that CUMS induced depression-like behavior and cognitive
deficits as the CUMS+vehicle (VEH) group showed a significant increase in
immobility in the tail suspension test, a decrease in the discrimination index of
the novel object recognition task, and increased latency to platform and
decreased number of platform crossings in the Morris water maze compared with the
control+VEH group. Chronic administration of BB effectively reversed these
alterations. In addition, the CUMS+VEH group showed significantly higher levels
of baseline serum corticosterone than those of the control+VEH group and BB dose
dependently inhibited this effect. Our results suggest that BB may be useful for
inhibition of depression-like behavior and cognitive deficits, and this
protective effect was possibly exerted partly through an action on the
hypothalamic-pituitary-adrenal axis.
PMID- 27509314
TI - Central antinociceptive effect of tapentadol is increased by nitric oxide
synthase inhibitors.
AB - Nitric oxide synthases (NOSs) have been shown to participate in the mechanism of
the antinociceptive action of tapentadol. The results obtained in this study
indicate that tapentadol administered intrathecally at a range of doses (30-100
ug) increased nociceptive thresholds in the Randall-Selitto and tail-flick tests
in rats; however, this effect was significant only for the higher doses. After
intracerebroventricular administration of tapentadol at the same dose range, an
antinociceptive effect was observed only in response to mechanical stimuli. In
coadministration studies, L-N-nitro arginine (L-NOArg) - a nonselective NOS
inhibitor as well as selective inhibitors: 7-Nitroindazole (7-NI), L-N(1
iminoethyl)lysine (L-NIL) or N-(1-iminoethyl)-L-ornithine (L-NIO) for the
respective neuronal, inducible, and endothelial NOSs enhanced the antinociceptive
activity of intrathecally administered tapentadol in the Randall-Selitto test and
to a lesser extent in the tail-flick test. A similar, although less pronounced
effect of intracerebroventricular tapentadol was also observed after previous
administration of NOS inhibitors in the Randall-Selitto test, but not in the tail
flick test. In conclusion, neuronal NOS, inducible NOS, and endothelial NOS
influence the antinociceptive action of tapentadol at the spinal level and to a
much lesser extent at the supraspinal level.
PMID- 27509315
TI - Lack of effect of ethanol on cocaine prime-induced reinstatement of extinguished
cocaine self-administration in rhesus monkeys.
AB - Cocaine and alcohol are commonly co-abused for reasons that are incompletely
understood. Laboratory animal studies have suggested that, although the
reinforcing effects of low cocaine doses are increased following chronic ethanol
(EtOH) consumption, acute EtOH administration does not consistently alter cocaine
self-administration. The present study examined whether EtOH influences another
abuse-related effect of cocaine: reinstatement of extinguished responding. Rhesus
monkeys that had previously consumed EtOH for 8 weeks (2.0 g/kg over 1 h, 5
days/week) self-administered up to 10 injections per day of 0.1 mg/kg cocaine
under a fixed-interval 300-s schedule. After responding had been extinguished by
substituting saline for cocaine, a pre-session infusion of saline or EtOH (0.5 or
1.0 g/kg, intravenously over 10 min) was followed by a 'priming' injection of
saline or cocaine (intravenously). Responding was increased significantly by
priming injections of cocaine, but not saline. EtOH infusions neither reinstated
behavior when administered before a saline prime nor altered the priming effect
of cocaine. The inability of EtOH to alter the response-reinstating ability of
cocaine provides further evidence for a lack of acute behavioral interactions
between cocaine and EtOH.
PMID- 27509317
TI - Nanotechnology for the diagnosis and treatment of diseases.
PMID- 27509316
TI - Punica granatum L. Juice Attenuates Experimental Cerebral Vasospasm in the Rabbit
Subarachnoid Hemorrhage Model: A Basilar Artery Morphometric Study and Apoptosis.
AB - Background This study investigated the effect of Punica granatum L. (pomegranate)
juice on the rabbit basilar artery in an experimental subarachnoid hemorrhage
(SAH) model. Methods Eighteen adult male New Zealand white rabbits were randomly
divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH +
treatment group (n = 6). Basilar artery diameter was measured with magnetic
resonance angiography (MRA) in all groups at the beginning of the study.
Experimental SAH was created by injecting autologous arterial blood into the
cisterna magna. In the treatment group, the subjects were administered a daily
dose of 30 ml/kg pomegranate juice via gastric gavage for 4 days after the SAH.
The SAH group and SAH + treatment group underwent cerebral MRA after 72 hours.
After a neurologic score assessment, all the animals were killed. The wall
thickness and lumen area of the basilar artery were measured histometrically in
all groups, and the apoptotic cell percentage in the artery was identified. The
mean diameter of the basilar artery during MRA was measured. Results Pomegranate
improved neurologic functions compared with the SAH group (p < 0.01). The mean
basilar artery diameter on MRA in the SAH + treatment group was larger than in
the SAH group and smaller than in the control group (p < 0.01 and p < 0.05,
respectively). The mean vessel wall thickness value in the SAH + treatment group
was lower than in the SAH group (p < 0.01), whereas there was no difference
between the control and the SAH + treatment group (p > 0.05). The apoptotic cell
rate in the SAH + treatment group was significantly lower than in the SAH group
(p < 0.001). Evaluation of the basilar artery luminal area showed no difference
between the three groups (p > 0.05). Discussion Pomegranate was shown to have a
vasospasm- attenuating effect on the basilar artery in the rabbit SAH model for
the first time in our study.
PMID- 27509318
TI - Characteristics of gay, bisexual and other men who have sex with men testing and
retesting at Australia's first shop-front rapid point-of-care HIV testing
service.
AB - BACKGROUND: HIV rapid point-of-care (RPOC) testing was approved in Australia in
2012 prompting new testing models. We describe gay, bisexual and other men who
have sex with men (GBM) testing in the first year of operations at Australia's
first shop-front, community-based RPOC testing service, PRONTO!, and characterise
return testers and first-time testers. METHODS: Univariable and multivariable
logistic regression using data collected at clients' first test at PRONTO! from
15 August 2013 to 14 August 2014 examined correlates of: 1) return-testing within
6 months of GBMs first test at PRONTO!; and 2) reporting a first ever HIV test at
PRONTO!. RESULTS: In the first year, 1226 GBM tested at PRONTO! (median age=30.4
years, 60.2% Australian born). Condomless anal sex with casual or regular
partners was reported by 45% and 66% of GBM, respectively. Almost one-quarter
(23%) of GBM returned within 6 months of their first test. Return-testing was
associated with being born overseas (adjusted odds ratio (AOR)=1.48, 95%
confidence interval (CI)=1.10-2.0), reporting a regular check-up as reason to
test (AOR=1.53, 95% CI=1.01-2.30) and reporting a HIV test in the 6 months before
first testing at PRONTO! (AOR=1.73, 95% CI=1.09-2.73). Reporting first testing at
PRONTO! (17.9%) was positively associated with younger age (<30 years; AOR=1.78,
95% CI=1.18-2.71) and negatively associated with reporting a regular check-up as
reason to test (AOR=0.45, 95% CI=0.29-0.71) and recent group sex (AOR=0.37, 95%
CI=0.23-0.59). CONCLUSION: Despite PRONTO! being designed to reduce barriers to
HIV testing, return testing rates in the first year were low and not associated
with client risk. Service refinements, including the provision of comprehensive
sexually transmissible infection testing, are needed to increase testing
frequency and enhance population HIV prevention benefits.
PMID- 27509319
TI - MIR196A2 rs11614913 C > T polymorphism correlates with an increased risk of
hepatopulmonary syndrome in liver cirrhosis: a case-control study in China.
AB - OBJECTIVE: This case-control study is designed to explore the relationship
between microRNA-196a2 (MIR196A2) rs11614913 C > T polymorphism and the risk of
hepatopulmonary syndrome (HPS) in liver cirrhosis. METHODS: From January 2013 to
January 2015, 163 liver cirrhosis patients with HPS (case group), 264 liver
cirrhosis patients without HPS (control group), and 195 healthy people (normal
group) were selected. A DNA extraction kit was used to extract plasma DNA from
peripheral blood. Polymerase chain reaction-restriction fragment length
polymorphism was used to detect the allele and genotype frequencies of MIR196A2 C
> T polymorphism. Real-time quantitative polymerase chain reaction was adopted to
detect the relative expression of MIR196A. RESULTS: The frequencies of C allele
in the case group were higher than those in the control and normal groups (all P
< 0.05), whereas no significant difference was found between the control and
normal groups, which indicated that MIR196A2 C > T polymorphism was closely
associated with an increased risk of HPS in patients with liver cirrhosis.
Compared with the normal group, the relative expression of MIR196A in the case
group was significantly increased (P < 0.05), but there was no significant
difference in the control group (P > 0.05). In the case group, compared with
patients carrying the TT genotype, the relative expression of MIR196A of patients
carrying the C allele (CT + CC) evidently increased (P < 0.05). CONCLUSIONS: The
MIR196A2 rs11614913 C > T polymorphism may contribute to an increased risk of HPS
in liver cirrhosis patients.
PMID- 27509320
TI - Complementary models reveal cellular responses to contact stresses that
contribute to post-traumatic osteoarthritis.
AB - Two categories of joint overloading cause post-traumatic osteoarthritis (PTOA):
single acute traumatic loads/impactions and repetitive overloading due to
incongruity/instability. We developed and refined three classes of complementary
models to define relationships between joint overloading and progressive
cartilage loss across the spectrum of acute injuries and chronic joint
abnormalities: explant and whole joint models that allow probing of cellular
responses to mechanical injury and contact stresses, animal models that enable
study of PTOA pathways in living joints and pre-clinical testing of treatments,
and patient-specific computational models that define the overloading that causes
OA in humans. We coordinated methodologies across models so that results from
each informed the others, maximizing the benefit of this complementary approach.
We are incorporating results from these investigations into biomathematical
models to provide predictions of PTOA risk and guide treatment. Each approach has
limitations, but each provides opportunities to elucidate PTOA pathogenesis.
Taken together, they help define levels of joint overloading that cause cartilage
destruction, show that both forms of overloading can act through the same
biologic pathways, and create a framework for initiating clinical interventions
that decrease PTOA risk. Considered collectively, studies extending from explants
to humans show that thresholds of joint overloading that cause cartilage loss can
be defined, that to at least some extent both forms of joint overloading act
through the same biologic pathways, and interventions that interrupt these
pathways prevent cartilage damage. These observations suggest that treatments
that decrease the risk of all forms of OA progression can be discovered. (c) 2016
Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
35:515-523, 2017.
PMID- 27509321
TI - Persistent aggregates in apheresis platelet concentrates are commonly collected
from donors with a history of aggregate donation.
AB - Platelet apheresis sometimes causes persistent aggregates (PA). This study (n =
211) shows that changing the apheresis settings to reach fixed product volumes
instead of yields does not influence PA incidence, even though PA products on
average contain more platelets than controls. Furthermore, logistic regression
was used to model if PA can be predicted on the basis of certain predonation
parameters. PA donation history was the only parameter retained, proving a strong
determinant of predictability [AUC = 0.735 (SE = 0.022)]. Consequently, donations
from a donor with previous PA history are 7.8 times more likely to contain PA
than from a donor without preceding history.
PMID- 27509322
TI - Kinetic and Theoretical Study of the Nitrate (NO3) Radical Gas Phase Reactions
with N-Nitrosodimethylamine and N-Nitrosodiethylamine.
AB - The reaction rates of (CH3)2NNO and (CH3CH2)2NNO with NO3 radicals were
determined relative to formaldehyde (CH2O) and ethene (CH2CH2) at 298 +/- 2 K and
1013 +/- 10 hPa in purified air by long path FTIR spectroscopy. The reactions are
too slow to be of importance at atmospheric conditions: kNO3+(CH3)2NNO = (1.47 +/
0.23) * 10(-16) and kNO3+(CH3CH2)2NNO = (5.1 +/- 0.4) * 10(-16) cm(3) molecule(
1) s(-1) (1sigma error limits). Theoretical calculations, based on CCSD(T*)
F12a/aug-cc-pVTZ//M06-2X/aug-cc-pVTZ results, predict the corresponding imines as
the sole primary products in nitrosamine reactions with NO3 and OH radicals.
PMID- 27509323
TI - Three rDNA Loci-Based Phylogenies of Tintinnid Ciliates (Ciliophora,
Spirotrichea, Choreotrichida).
AB - To improve understanding of diversity, phylogeny and evolution in tintinnid
ciliates, it is essential to link multiple molecular markers with properly
identified and documented morphospecies. Accordingly, 54 tintinnid
morphospecies/isolates mainly from the Yellow and East China Seas were collected
and analysed. Using single-cell approaches, sequences were obtained for three
rDNA loci (18S, ITS1-5.8S-ITS2, D1-D5 region of 28S). Twenty-six tintinnid
morphospecies (29 isolates) are documented by micrographs, measurements,
morphologically described, and compared with the original species description.
Three rDNA loci-based phylogenetic analyses were then performed for these
identified isolates. Sequences from 25 unidentified species/isolates were also
included in the comparison of the three rDNA loci. Ribosomal DNA genes of the
genus Leprotintinnus were analysed for the first time, showing that
Leprotintinnus was closely related to Tintinnopsis radix and branched distinctly
apart from the family Tintinnidiidae. Four novel clades (VI to IX) of the
Tintinnopsis complex emerged in the 18S genealogies. Analyses of the relative
variability in the ITS and 28S regions vs. the 18S rDNA showed that the ITS1-5.8S
ITS2 and ITS2 regions well co-varied with the 18S rDNA when the variations of the
latter were less than 3%, whereas at difference of less than 1%, no correlation
was found between the compared loci. These findings highlight the difficulties in
using variable locus-based cut-off divergences in circumscribing tintinnid
morphospecies.
PMID- 27509325
TI - Robotic liver donor right hepatectomy: A pure, minimally invasive approach.
AB - Right hepatectomy for a living liver donor via a pure minimally invasive approach
is a challenging procedure and only a few cases have been reported. Between May
2013 and August 2015, 13 patients underwent robotic living donor right
hepatectomy in our institute, and 54 patients received open surgery. In this
series, no conversion was conducted for robotic donor right hepatectomy. The 2
groups shared similar blood loss (169 versus 146 mL), complication rates (7.7%
versus 9.3%), and recovery of donor liver function (peak alanine
aminotransferase, 269 versus 252 IU/mL). The robotic group needed longer
operation time (596 versus 383 minutes) but less postoperative patient-controlled
analgesia (0.58 versus 0.84 ng/kg) and a shorter period before returning to
work/school (52.9 versus 100.0 days) and sex (100.0 versus 156.0 days). For
recipient outcomes regarding the donor procedure, the robotic group shared
similar experiences in early allograft dysfunction, complications, and 1-year
recipient liver function with the open group. With respect to documented benefits
of minimally invasive left-sided liver donor procedure, the development of right
donor hepatectomy is slow. In conclusion, with substantial improvements in
patient recovery after the minimally invasive approach, the robotic platform
would be a big step toward completing pure minimally invasive liver donor
surgery. Liver Transplantation 22 1509-1518 2016 AASLD.
PMID- 27509326
TI - Carbon-Decorated TiO2 Nanotube Membranes: A Renewable Nanofilter for Charge
Selective Enrichment of Proteins.
AB - In this work, we design a TiO2 nanomembrane (TiNM) that can be used as a
nanofilter platform for selective enrichment of specific proteins. After a first
use, the photocatalytic properties of TiO2 allow the decomposition of unwanted
remnants on the substrate and thus make the platform reusable. To construct this
platform, we fabricate a free-standing TiO2 nanotube array and remove the bottom
oxide to form a both-end-open TiNM. By pyrolysis of the natural tube wall
contamination, the walls become decorated with graphitic carbon patches (C/TiNM).
Owing to the large surface area, the amphiphilic nature and the charge-adjustable
character, this C/TiNM can be used to extract and enrich hydrophobic charged
biomolecules. Using human serum albumin (HSA) as a model protein as well as
protein mixtures, we show that the composite membrane exhibits a highly enhanced
loading capacity and protein selectivity and is reusable after a short UV
treatment.
PMID- 27509327
TI - Osteolysis Complicating Total Knee Arthroplasty.
AB - Osteolysis is a process mounted by the host immune system that relies on several
variables, including patient-related factors, type of insert material, modes of
wear, and implant design. Imaging techniques such as radiography, computed
tomography (CT) scans, magnetic resonance imaging (MRI), and tomosynthesis aid in
diagnosing osteolysis. Surgical options for the treatment of osteolysis include
the insertion of bone grafts, bone cement, and prosthetic augmentation. Although
no approved pharmacological therapies for the specific treatment of osteolysis
exist, the use of bisphosphonates and statins decreases the risk of osteolysis.
PMID- 27509328
TI - Treatment of Osteonecrosis of the Talus.
AB - More than 60% of the talar surface area consists of articular cartilage, thereby
limiting the possible locations for vascular infiltration and leaving the talus
vulnerable to osteonecrosis. Treatment strategies for talar osteonecrosis can be
grouped into four categories: nonsurgical, surgical-joint sparing, surgical
salvage, and joint-sacrificing treatments. Nonoperative and joint-sparing
treatments include restricted weight-bearing, patellar tendon-bearing braces,
bone-grafting, extracorporeal shock wave therapy, internal implantation of a bone
stimulator, core decompression, and vascularized or non-vascularized autograft,
whereas joint-sacrificing or salvage procedures include talar replacement
(partial or total) and arthrodesis. In patients with a Ficat and Arlet grade-I
through III osteonecrosis, evidence in favor of a specific treatment is poor,
although tibiotalar or tibiotalocalcaneal arthrodesis may represent a suitable
salvage operation.
PMID- 27509329
TI - The Pathogenesis and Treatment of Legg-Calve-Perthes Disease.
AB - Legg-Calve-Perthes disease is a childhood hip condition in which the blood supply
to the capital femoral epiphysis is interrupted, causing osteonecrosis and
chondronecrosis that lead to progressive deformity of the femoral head and
secondary degenerative osteoarthritis in later life. The etiology of Legg-Calve
Perthes disease remains unclear, with both biological and mechanical factors
playing important roles in the pathogenesis of the condition. The treatment of
Legg-Calve-Perthes disease remains controversial but is dependent on several
salient factors, including the age at clinical onset, the extent of epiphyseal
involvement, the stage of the disease, and the degree of femoral head deformity.
The literature supports operative containment treatment in the early stage of
disease. Such treatment has led to improved femoral head sphericity with better
patient outcomes in multicenter prospective cohort studies. The number of hips
that need to be treated operatively in order to achieve a modest treatment effect
remains high. Multicenter prospective cohort studies have shown that 6 to 7
patients need to be managed to create 1 spherical femoral head that would not
have otherwise occurred.
PMID- 27509330
TI - Team Approach: Treatment of Diabetic Foot Ulcer.
AB - At any point in time, 3% to 4% of the 29.1 million diabetic patients in the
United States (9.3% of the population) will have a foot ulcer. Diabetes
associated foot ulcers and infection lead to >70,000 lower-extremity amputations
yearly in the United States. Between one-third and one-half of diabetic patients
undergoing a major lower-extremity amputation will die within 2 years after the
amputation. Multidisciplinary population health-management strategies have been
developed to decrease the rate and magnitude of this important comorbidity in the
diabetic population. The goal of the present review is to provide the reader with
a framework for the development of a health-care-system strategy for addressing
this complex patient population.
PMID- 27509331
TI - Pigmented Villonodular Synovitis: A Comprehensive Review and Proposed Treatment
Algorithm.
AB - Evidence now exists suggesting a neoplastic origin for pigmented villonodular
synovitis, including a thorough description of the translocations involved.
Arthroscopic excision for localized pigmented villonodular synovitis allows for
both minimal recurrence and morbidity when compared with open excision; however,
open excision still plays an important role in treating posterior compartment
nodules. The optimal surgical treatment for diffuse pigmented villonodular
synovitis is still a matter for debate, with combined anterior arthroscopic and
open posterior excision being considered the preferred method. Radiation therapy
has re-emerged as an additional treatment method for pigmented villonodular
synovitis; however, the potential for serious toxicity makes it a questionable
option, especially for such a benign condition. Small molecule and monoclonal
antibody targeted therapies are being investigated as novel treatment methods for
pigmented villonodular synovitis, with promising results.
PMID- 27509332
TI - Biosensing Test-Bed Using Electrochemically Deposited Reduced Graphene Oxide.
AB - The development of an efficient test-bed for biosensors requires stable surfaces,
capable of interacting with the functional groups present in bioentities. This
work demonstrates the formation of highly stable electrochemically reduced
graphene oxide (ERGO) thin films reproducibly on indium tin oxide (ITO)-coated
glass substrates using a reliable technique through 60 s chronoamperometric
reduction of a colloidal suspension maintained at neutral pH containing graphene
oxide in deionized water. Structural optimization and biocompatible interactions
of the resulting closely packed and uniformly distributed ERGO flakes on ITO
surfaces (ERGO/ITO) are characterized using various microscopic and spectroscopic
tools. Lipase enzyme is immobilized on the ERGO surface in the presence of ethyl
3-[3-(dimethylamino)propyl]carbodimide and N-hydroxysuccinimide for the detection
of triglyceride in a tributyrin (TBN) solution. The ERGO/ITO surfaces prepared
using the current technique indicate the noticeable detection of TBN, a source of
triglycerides, at a sensitivity of 37 pA mg dL(-1) cm(-2) in the linear range
from 50 to 300 mg dL(-1) with a response time of 12 s. The low apparent
Michaelies-Menten constant of 0.28 mM suggests high enzyme affinity to TBN. The
currently developed fast, simple, highly reproducible, and reliable technique for
the formation of an ERGO electrode could be routinely utilized as a test bed for
the detection of clinically active bioentities.
PMID- 27509333
TI - Molecular differences in the microsatellite stable phenotype between left-sided
and right-sided colorectal cancer.
AB - Differences in the pathogenesis of microsatellite stable (MSS) sporadic
colorectal cancers (CRCs) between left-sided CRC (LC) and right-sided CRC (RC)
have not been clarified. To identify pathogenesis-related genomic differences
between MSS CRCs within the two locations, we performed a comprehensive molecular
analysis using crypt isolation with samples from 92 sporadic CRCs. Microsatellite
instability (MSI; high and low/negative) and DNA methylation status (low
methylation epigenome; intermediate methylation epigenome [IME] or high
methylation epigenome [HME]) were determined using polymerase chain reaction
(PCR) microsatellite analysis and PCR-bisulfite pyrosequencing, respectively.
Additionally, mutations in the TP53, KRAS, BRAF and PIK3CA genes were examined
using PCR-bisulfite pyrosequencing (for KRAS and BRAF mutations) or PCR-single
conformation polymorphism (for TP53 and PIK3CA mutations), followed by sequencing
of aberrant bands. Finally, a genome-wide study using a copy number alteration
(CNA)-targeted single nucleotide polymorphism array was performed. Ninety-two
CRCs were classified into 71 MSS and 21 MSI phenotypes. We examined 71 CRCs with
the MSS phenotype (LC, 56; RC, 15). Mutations in KRAS were associated with RC
with the MSS phenotype, whereas mutations in TP53 were more frequently found in
LC with the MSS phenotype. There were significant differences in the frequencies
of KRAS and TP53 mutations in the IME between LC and RC with the MSS phenotype.
Although CNA gains were associated with LC with the MSS phenotype, CNA losses
were not major alterations associated with the MSS phenotype. These findings
suggested that the molecular pathogenesis of the MSS phenotype in LC was
different from that in RC.
PMID- 27509334
TI - Integrative review: nurses' roles and experiences in keeping children safe.
AB - AIM: To identify nurses' role and experiences of keeping children safe.
BACKGROUND: Approaches to preventing, identifying and responding to child abuse
and neglect have moved towards a multidisciplinary approach where all
professionals are expected to contribute to the goal of keeping children safe.
Frequently in contact with children and families, nurses well positioned to
contribute to keeping children safe from abuse and neglect. Much has been
published around nurses' experiences of their role in keeping children safe, but
this literature has not yet been synthesized to determine the challenges and
potential scope of this role. DESIGN: Integrative review following an Integrative
Review framework. DATA SOURCES: Studies were identified through a search of the
electronic databases CINAHL, Medline, Web of Science, Scopus and Informit to
identify literature published between 2005-2015. REVIEW METHODS: All the studies
were critically appraised for methodological quality using the Critical Skills
Appraisal Programme. Data from each study were extracted and categorized
according to the review aims and the study's major findings. RESULTS: Inclusion
criteria were met in 60 studies. Three main findings were identified including
nurses' insufficient knowledge, need for validation and improved communication
and balancing surveillance and support for vulnerable families. CONCLUSIONS:
Nurses have many roles and experiences in keeping children safe but often felt
they did not have the knowledge, skills and support to take action in this area.
Further research is needed to understand why nurses feel inadequate and
disempowered to advocate and intervene on the behalf of children at risk of abuse
or neglect.
PMID- 27509336
TI - [Discussion of values in health care: a crucial test for internal medicine?].
PMID- 27509335
TI - Biological and biophysics aspects of metformin-induced effects: cortex
mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar
aggregates.
AB - The onset of Alzheimer disease (AD) is influenced by several risk factors
comprising diabetes. Within this context, antidiabetic drugs, including
metformin, are investigated for their effect on AD. We report that in the C57B6/J
mice, metformin is delivered to the brain where activates AMP-activated kinase
(AMPK), its molecular target. This drug affects the levels of beta-secretase
(BACE1) and beta-amyloid precursor protein (APP), promoting processing and
aggregation of beta-amyloid (Abeta), mainly in the cortex region. Moreover,
metformin induces mitochondrial dysfunction and cell death by affecting the level
and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage
dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins
involved in mitochondrial transport of molecules, including Abeta. By using
biophysical techniques we found that metformin is able to directly interact with
Abeta influencing its aggregation kinetics and features. These findings indicate
that metformin induces different adverse effects, leading to an overall increase
of the risk of AD onset.
PMID- 27509337
TI - [Renal artery stenosis: new insights and developments].
PMID- 27509338
TI - [Subclinical hypothyroidism - laboratory finding or disease?].
AB - Subclinical hypothyroidism first of all is a laboratory finding, defined by
elevated TSH and normal peripheral thyroxine concentrations. The first steps are
to verify the condition and to clarify whether the patient has underlying thyroid
disease or other comorbidities. Results of recent studies on subclinical
hypothyroidism are reassuring. No consistent association has been demonstrated
between mildly elevated TSH levels (5-10 mIU / l) and cardiovascular events,
mortality, fracture risk or cognitive impairment. In contrast TSH levels between
5-10 mIU / l may even confer lower mortality in the elderly and may hence be
protective. These data strongly suggest that the long-time controversy on
definition of normal upper TSH levels should take a more conservative turn. Thus,
diagnosis of subclinical hypothyroidism should be handled cautiously.
Individualized treatment decision is recommended if TSH levels are only mildly
elevated and less than 8-10 mIU / l. In case of autoimmune thyroiditis or
previous thyroid therapy (surgery, radioiodine treatment) the risk of progression
to overt hypothyroidism has to be considered and there is no doubt that the
latter should be avoided.
PMID- 27509339
TI - [Sleep Disturbances in the Elderly].
AB - Sleep disturbances are common in the elderly. Endogen regulation mechanisms are
often unstable. Light treatment and melatonin are proved chronobiological
interventions. Cataract surgery is effective to enhance the sleep-wake
rhythm.Mandibular advancement devices are a reliable alternative to continuous
positive air pressure (CPAP) in obstructive sleep apnea syndrome (OSAS).
PMID- 27509340
TI - [Hemophagocytic lymphohistiocytosis in adults].
AB - Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome
with established diagnostic criteria, and well characterized gene mutations in
children. In contrast, acquired HLH in adults (aHLH) due to the heterogeneity of
trigger diseases (infections, malignancies and autoimmune diseases) is less clear
defined. There is both a risk of under- and overtreatment. Due to the lack of
validated diagnostic criteria for HLH in adults, diagnostic and therapeutic delay
are significant risk factors for patient outcome. This article presents the
current status and new developments in epidemiology, pathophysiology, diagnosis
and treatment of aHLH.
PMID- 27509341
TI - [New aspects on Clostridium difficile infection].
AB - Clostridium difficile infection (CDI) is a frequent and complex disease which is
influenced by the repertoire of bacterial virulence factors, by host immunity and
by the intestinal microbiome. These complex interaction opens a number of options
which may be used for treatment in the future. One example for new treatment
options is fecal microbiota transplantation (FMT). Driven by C. difficile related
research activities the knowledge of protective microorganism is increasing and
it may be assumed that bacteriotherapy by next-generation probiotics may be used
very soon also for other diseases. Very often, CDI reflects to the clinician that
antibiotic therapy is associated with side effects. Therefore, C. difficile is
the guilty conscience which helps to implement targeted and restrictive
antibiotic use in the daily practice.
PMID- 27509342
TI - [Airway Management In Intensive Care Patients].
AB - Many physicians are working in intensive care and are not additionally
anaesthesiological experienced. The situation having to perform an emergency in
intubation is often feel anxious. Significant complications, such as severe
hypoxemia (25%), life-threatening cardiovascular events (40%) or cardiac arrest
(2%) may occur during intubation on ICU. The physician must have a clear strategy
in preparation and implemention of emergency intubation. It is equally important
to perform an alternative airway management when intubation is difficult.In the
last 15 years we became aware of this problem and established clear guidelines
and algorithms. Drug innovations, technical innovations and new workflows improve
complications and mortality rates and provide security. This article describes
the current innovations and study results for intubation of criticall ill
patients.
PMID- 27509343
TI - [Treatment of ventricular tachyarrhythmias and prevention of sudden cardiac
death: commentary on the 2016 ESC guideline].
AB - The 2016 ESC guideline on prevention and therapy of ventricular tachyarrhythmias
and sudden cardiac death present an excellent recommendation and summary for all
forms of ventricular tachyarrhythmias in patients with and without structural or
electrical heart disease. This includes cardiomyopathies as well as conditions
such as proarrhythmia, neurologic/psychaitric disorders, or pregnancy. Some
aspects are novel; (1) the guideline emphasizes for the first time genetic work
up in sudden cardiac death victims; (2) for prevention of sudden cardiac death
systematic re-evaluation 6-12 weeks after myocardial infarction is recommended;
(3) subcutaneous ICD as well as the wearable cardioverter/defibrillator are for
the first time included in the guidelines; (4) automatic external defibrillators
are recommended for public places; (5) for patients with recurrent ventricular
tachyarrhythmias the role of catheter ablation has been upgraded.
PMID- 27509344
TI - [Primary and secondary glomerular diseases].
PMID- 27509345
TI - [Asthma COPD Overlap Syndrome (ACOS): precision medicine or diagnostic dead
end?].
AB - Asthma and COPD are two distinct diseases but sometimes patient can show clinical
features of asthma and COPD. For this group the term asthma-COPD-overlap syndrome
(ACOS) has been created. However, the variability of defining criteria leads to a
broad heterogeneity of patients assigned to this syndrome. Therefore, the
introduction of the term ACOS is of limited value for a more individualized
treatment of patients with obstructive airway disease.
PMID- 27509346
TI - [An update on gout: diagnostic approach, treatment and comorbidity].
AB - Muskuloskeletal ultrasound and dual-energy-CT (DECT) findings are increasingly
relevant for the establishment of the diagnosis of gout, and are therefore
incorporated into the novel ACR / EULAR classification criteria. Canakinumab, a
monoclonal antibody directed against interleukin-1beta (IL-1beta) has been
approved in 2013 for the treatment of acute gout and for prophylaxis of flares.
In patients demonstrating an inadequate response upon treatment with allopurinol
or febuxostat, combination therapy with lesinurad might reduce uric acid levels
to the target of < 6 mg / dl (< 5 mg / dl in tophaceous gout). Rapid lowering of
uric acid levels and effective tophi reduction can be achieved with pegloticase,
which can be utilized in selected patients presenting contraindications to
xanthine oxidase inhibitors and uricosuric drugs. This article summarizes current
scientific aspects of diagnosis, treatment and comorbidities of gout in the
context of clinical relevance.
PMID- 27509347
TI - [Recent therapeutic options of (severe) gastrointestinal bleedings].
AB - With Idarucizumab, a specific antidote to antagonize the effect of dabigatran, is
now available in severe bleeding complications under directly oral anticoagulants
(DOAC). In endoscopic treatment of severe gastrointestinal bleeding are
alternative treatment options also available with hemostasis sprays and new
hemostasis clips. Especially in recurrent ulcer bleedings, the newly developed
clips can achieve hemostasis and prevent an operational procedure. In patients
with coronary heart disease, a liberal transfusion regimen should be considered.
PMID- 27509348
TI - [42-year old man with sudden, progredient dyspnea].
PMID- 27509349
TI - [Acute liver failure after ingestion of ciprofloxacin].
AB - HISTORY AND ADMISSION FINDINGS: A 23-year old female patient is referred to our
intensive care unit from another hospital because of progredient neurological
deterioration with sopor. One week before, she had experienced non-specific pain
in her upper right stomach combined with vomitus and nausea. For two days, she
had been treated with ciprofloxacin 2 * 500 mg / d by her primary care physician.
Except for appendectomy in childhood, no other diseases were reported. Clinical
investigation: Physical examination reveals mild scleral and dermal jaundice.
There is tenderness of the upper right abdomen. Initially, no neurological
pathological findings are obvious. Laboratory results show an increase of liver
aminotransferases, bilirubin, and ammonia. The toxicological screening is
negative. TREATMENT AND COURSE: Hepatic encephalopathy due to acute hepatic
failure is diagnosed and detoxification of ammonia with lactulose is started.
Transiugular liver biopsy confirms lobular hepatitis with cytolysis. Because of
progressive deterioration additional treatment to prevent cerebral oedema is
initiated. Consecutively serum osmolality decreases, and ammonia and neurological
status normalize. CONCLUSION: This report illustrates toxic acute liver failure
after treatment with ciprofloxacin.
PMID- 27509350
TI - [Constipation in Patients with Incurable Cancer - Recommendations of the German
S3 Guideline 'Palliative Medicine'].
AB - According to the German S3-guideline 'Palliative Medicine' which has been
supported by the German Guideline Program in Oncology, constipation in palliative
patients requires a consistent prophylaxis and therapy. Constipation is caused by
immobilisation, poor health, exsiccosis, a low-fiber diet or a preexisting
functional constipation. Further important causes are substances with
constipating side effects, such as opioids or anticholinergic drugs.
Pragmatically, constipation should be assessed by subjective parameters such as
the feeling of incomplete evacuation, straining, or other complaints. Objective
parameters are hard stool or reduced number of bowel movements. For the early
detection of constipation the amount of the stool mass and the stool frequency
are applicable. If constipation occurs, a standardized escalating protocol
applying adequate fluid intake, a high fibre diet, and laxatives is recommended.
New prokinetic agents, secretagogues, or opioid antagonists may be used as
reserve drugs.
PMID- 27509351
TI - Adaptive Design for a Confirmatory Basket Trial in Multiple Tumor Types Based on
a Putative Predictive Biomarker.
AB - Increasingly, tumors are defined on a molecular basis rather than only on
histology, and targeted agents, which address these molecular subtypes, are being
approved. This profusion of molecular subtypes creates "rare" diseases as subsets
of common cancers, leading to difficulties in enrolling sufficiently large
cohorts for confirmatory trials. However, if the molecular subtype is shared
across various histologies, these may be pooled into a basket trial. To date,
basket trials have been primarily for exploratory early development. In this
perspective, we consider qualitative designs for confirmatory basket trials.
These confirmatory basket designs will provide patients in niche indications with
enhanced access to novel therapies, facilitate development and full approval for
niche indications, allow accelerated approval for indications within a basket
based on a surrogate endpoint, reduce development cost by combining trials, and
enhance the ability of regulatory authorities to evaluate risk and benefit in
niche indications.
PMID- 27509352
TI - Impulsive choices in mice lacking imprinted Nesp55.
AB - Genomic imprinting is the process whereby germline epigenetic events lead to
parent-of-origin specific monallelic expression of a number of key mammalian
genes. The imprinted gene Nesp is expressed from the maternal allele only and
encodes for Nesp55 protein. In the brain, Nesp55 is found predominately in
discrete areas of the hypothalamus and midbrain. Previously, we have shown that
loss of Nesp55 gives rise to alterations in novelty-related behaviour. Here, we
extend these findings and demonstrate, using the Nespm/+ mouse model, that loss
of Nesp55 leads to impulsive choices as measured by a delayed-reinforcement task,
whereby Nespm/+ mice were less willing to wait for a delayed, larger reward,
preferring instead to choose an immediate, smaller reward. These effects were
highly specific as performance in another component of impulsive behaviour, the
ability to stop a response once started as assayed in the stop-signal reaction
time task, was equivalent to controls. We also showed changes in the serotonin
system, a key neurotransmitter pathway mediating impulsive behaviour. First, we
demonstrated that Nesp55 is co-localized with serotonin and then went on to show
that in midbrain regions there were reductions in mRNA expression of the
serotonin-specific genes Tph2 and Slc6a4, but not the dopamine-specific gene Th
in Nespm/+ mice; suggesting an altered serotonergic system could contribute, in
part, to the changes in impulsive behaviour. These data provide a novel mode of
action for genomic imprinting in the brain and may have implications for
pathological conditions characterized by maladaptive response control.
PMID- 27509353
TI - Antimicrobial activity of submicron glass fibres incorporated as a filler to a
dental sealer.
AB - Two types of antimicrobial glass fibers containing ZnO and CaO, with diameters
ranging from tens of nanometers to 1 um, were successfully fabricated by a laser
spinning technique. The antimicrobial performance was corroborated according to
ISO 20743:2013, by using gram-negative (Escherichia coli) and gram-positive
(Streptococcus oralis, Streptococcus mutans and Staphylococcus aureus) bacteria,
and yeast (Candida krusei) (more than 3 logs of reduction). The metabolic
activity and endosomal system of eukaryotic cells were not altered by using
eluents of CaO glass submicrometric fibers and ZnO fibers at 1 : 10 dilution as
cellular media (viability rates over 70%). A dental material was functionalized
by embedding ZnO nanofibers above the percolation threshold (20% wt), creating a
three-dimensional (3D) fiber network that added an antimicrobial profile. This
new ZnO glass fiber composite is proved non-cytotoxic and preserved the
antimicrobial effect after immersion in human saliva. This is the first time that
a fiber-reinforced liner with strong antimicrobial-activity has been created to
prevent secondary caries. The potential of developing new fiber-reinforced
composites (FRCs) with antimicrobial properties opens up an extensive field of
dental applications where most important diseases have an infectious origin.
PMID- 27509354
TI - Paranasal sinus opacification-to-pneumatization ratio applied as a rapid and
validated clinician assessment.
AB - BACKGROUND: The utility of clinician-applied instruments, particularly the Lund
Mackay score, in the assessment of paranasal sinus computed tomography (CT) in
chronic rhinosinusitis (CRS) remains incompletely defined. The purpose of this
study was to determine if a new approach to the evaluation of sinus CT could
accurately predict the extent of opacification while remaining simple for
clinician use. METHODS: Twenty-four sinus CT scans were measured for the percent
of sinus opacification using three-dimensional (3D) volumetric analyses. The same
scans were also evaluated using the Lund-Mackay score to measure opacification
and the Assessment of Pneumatization of the Paranasal Sinuses (APPS) score to
measure total sinus volume (TSV). Correlation analysis was performed for the Lund
Mackay to APPS score ratio as a predictor of percent opacification. Validation
analysis was also performed to determine the optimal orientation for Lund-Mackay
scoring, which has not previously been described. RESULTS: The Lund-Mackay to
APPS score ratio was very strongly correlated with the percentage of sinus
opacification measured by 3D volumetric analysis (r = 0.862, r2 = 0.743, p <
0.001). Lund-Mackay scoring was not statistically different between axial-only,
coronal-only, or triplanar groups for interrater (p = 0.379) and intrarater
reliability (p = 0.312). CONCLUSION: The Lund-Mackay score is validated for rater
reliability in multiple orientations. Using the APPS score as a measure of TSV,
the Lund-Mackay-to-APPS ratio very strongly correlates with the percentage of
sinus opacification by 3D volumetric analysis. Further study will be required to
determine if this ratio is predictive of symptom severity.
PMID- 27509355
TI - Cardiogenic Shock: Failure of Oxygen Delivery and Oxygen Utilization.
AB - Cardiogenic shock remains a highly lethal condition. Conventional therapy
including revascularization and mechanical circulatory support aims to improve
cardiac output and oxygen delivery, but increasing basic and clinical
observations indicate wider circulatory and cellular abnormalities, particularly
at the advanced stages of shock. Progressive cardiogenic shock is associated with
microcirculatory and cellular abnormalities. Cardiogenic shock is initially
characterized by a failure to maintain global oxygen delivery; however,
progressive cardiogenic shock is associated with the release of pro-inflammatory
cytokines, derangement of the regulation of regional blood flow, microcirculatory
abnormalities, and cellular dysoxia. These abnormalities are analogous to septic
shock and may not be reversed by increase in oxygen delivery, even to supranormal
levels. Earlier mechanical circulatory support in cardiogenic shock may limit the
development of microcirculatory and cellular abnormalities.
PMID- 27509356
TI - Short duration response-guided treatment is effective for most individuals with
recent hepatitis C infection: the ATAHC II and DARE-C I studies.
PMID- 27509358
TI - alpha-Glucosidase and alpha-Amylase Inhibitors from Arcytophyllum thymifolium.
AB - Three new coumarins (1-3), a prenylated flavanone (4), and two iridoids (5 and
6), together with 17 known secondary metabolites, were isolated from the aerial
parts of Arcytophyllum thymifolium. The structures of the new compounds were
elucidated on the basis of their spectroscopic data. The potential hypoglycemic
properties of the new and known compounds were evaluated by measuring their alpha
amylase and alpha-glucosidase inhibitory effects. The iridoid asperulosidic acid
(15) and the flavonoid rhamnetin (13) showed the highest activities versus alpha
amylase (IC50 = 69.4 +/- 3.1 and 73.9 +/- 5.9 MUM, respectively). In turn, the
new eriodictyol derivative 4 exhibited the most potent effect as an alpha
glucosidase inhibitor, with an IC50 value of 28.1 +/- 2.6 MUM, and was more
active than acarbose, used as a positive control. Modeling studies were also
performed to suggest the interaction mode of compound 4 in the alpha-glucosidase
enzyme active site.
PMID- 27509360
TI - Catalyst-Free and Regioconvergent Substitution Reactions of Bromothiophenes with
a BH3-Substituted Phosphide Anion.
AB - A range of bromothiophenes reacted with lithium boranato(tert
butyl)methylphosphide in the absence of transition-metal catalysts under mild
conditions to provide the same 2,5-disubstituted and 2-monosubstituted products
regardless of the substitution patterns of the starting bromothiophenes.
PMID- 27509359
TI - Lung Function in African Infants in the Drakenstein Child Health Study. Impact of
Lower Respiratory Tract Illness.
AB - RATIONALE: Lower respiratory tract illness is a major cause of childhood
morbidity and mortality. It is unknown whether infants are predisposed to illness
because of impaired lung function or whether respiratory illness reduces lung
function. OBJECTIVES: To investigate the impact of early life exposures,
including lower respiratory tract illness, on lung function during infancy.
METHODS: Infants enrolled in the Drakenstein child health study had lung function
at 6 weeks and 1 year. Testing during quiet natural sleep included tidal
breathing, exhaled nitric oxide, and multiple breath washout measures. Risk
factors for impaired lung health were collected longitudinally. Lower respiratory
tract illness surveillance was performed and any episode investigated.
MEASUREMENTS AND MAIN RESULTS: Lung function was tested in 648 children at 1
year. One hundred and fifty (29%) infants had a lower respiratory tract illness
during the first year of life. Lower respiratory tract illness was independently
associated with increased respiratory rate (4%; 95% confidence interval [CI],
1.01-1.08; P = 0.02). Repeat episodes further increased respiratory rate (3%; 95%
CI, 1.01-1.05; P = 0.004), decreased tidal volume (-1.7 ml; 95% CI, -3.3 to -0.2;
P = 0.03), and increased the lung clearance index (0.13 turnovers; 95% CI, 0.04
0.22; P = 0.006) compared with infants without illness. Tobacco smoke exposure,
lung function at 6 weeks, infant growth, and prematurity were other independent
predictors of lung function at 1 year. CONCLUSIONS: Early life lower respiratory
tract illness impairs lung function at 1 year, independent of baseline lung
function. Preventing early life lower respiratory tract illness is important to
optimize lung function and promote respiratory health in childhood.
PMID- 27509361
TI - Challenging the One-Dose-Fits-All Model for Insulin in the Acute Treatment of
Pediatric Diabetic Ketoacidosis. A Critical Appraisal of "Low-Dose Versus
Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A Randomized Clinical
Trial" by Nallasamy et al (JAMA Pediatrics 2014; 168:999-1005).
AB - OBJECTIVE: To review the findings and discuss the implications of the use of low
dose insulin infusions in pediatric diabetic ketoacidosis compared with standard
dose insulin. DATA SOURCES: A search of the electronic PubMed database was used
to perform the clinical query as well as to search for additional relevant
literature. STUDY SELECTION AND DATA EXTRACTION: The article by Nallasamy K et al
"Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A
Randomized Clinical Trial. JAMA Pediatrics 2014; 17:e477-e480" was selected for
critical appraisal and literature review. DATA SYNTHESIS: The authors performed a
randomized controlled trial among 50 consecutive patients of 0-12 years old
presenting to the emergency department in diabetic ketoacidosis. They found that
low-dose (0.05 U/kg/hr) insulin infusion was noninferior to standard-dose (0.1
U/kg/hr) insulin in terms of resolution of hyperglycemia and acidosis with a
trend toward lower rates of therapy-related complications in the low-dose group.
CONCLUSIONS: Low-dose insulin infusion is noninferior to standard-dose insulin in
the treatment of younger pediatric patients with diabetic ketoacidosis and may
lead to fewer therapy-related complications.
PMID- 27509362
TI - Enteral Nutrition and Acid-Suppressive Therapy in the PICU: Impact on the Risk of
Ventilator-Associated Pneumonia.
AB - OBJECTIVE: Enteral nutrition has been implicated as a risk factor for ventilator
associated pneumonia. We explored the prevalence of ventilator-associated
pneumonia and its association with clinical and nutrition-related therapies in
mechanically ventilated children. DESIGN: Prospective, multicenter, cohort study.
SETTING: Fifty-nine PICU in 15 countries. PATIENTS: Children less than 18 years
old, mechanically ventilated for more than 48 hours. INTERVENTIONS: None.
Multivariable logistic regression to determine factors associated with ventilator
associated pneumonia. MEASUREMENTS AND MAJOR RESULTS: Data are presented as
median (interquartile range) or counts (%). We enrolled 1,245 subjects (45%
women; 42% surgical), age 20 months (4-84 mo), and duration of mechanical
ventilation 7 days (3-13 d). Culture-positive ventilator-associated pneumonia was
diagnosed in 80 patients (6.4%); duration of mechanical ventilation for this
subgroup was 17 days (8-39 d). Enteral nutrition was delivered in 985 patients
(79%), initiated within 48 hours in 592 patients (60%), and via postpyloric route
in 354 patients (36%). Acid-suppressive agents were used in 763 patients (61%).
The duration of enteral nutrition (p = 0.21), route (gastric vs postpyloric) of
delivery (p = 0.94), severity of illness (p = 0.17), and diagnostic category on
admission (p = 0.31) were not associated with ventilator-associated pneumonia.
After adjusting for enteral nutrition days, illness severity, and site,
ventilator-associated pneumonia was significantly associated with mechanical
ventilation more than 10 days (odds ratio, 3.7; 95% CI, 2.2-6.5; p < 0.001), PICU
length of stay more than 10 days (odds ratio, 1.8; 95% CI, 1.1-3.1; p = 0.029),
and the use of acid-suppressive medication (odds ratio, 2.0; 95% CI, 1.2-3.6; p =
0.011). CONCLUSIONS: Ventilator-associated pneumonia was diagnosed in 6.5% of
mechanically ventilated children in a heterogeneous multicenter cohort. We did
not find a link between enteral nutrition duration or route of delivery and
ventilator-associated pneumonia. In addition to duration of mechanical
ventilation and length of PICU stay, the use of acid-suppressive therapy
independently increased the likelihood of developing ventilator-associated
pneumonia in this population. This association must be further explored in
clinical trials.
PMID- 27509363
TI - Admission PaO2 and Mortality in Critically Ill Children: A Cohort Study and
Systematic Review.
AB - OBJECTIVE: To describe the relationship between PaO2 at intensive care admission
and mortality in critically ill children and to review systematically the
literature describing this relationship. DESIGN: Cohort study: A review of
consecutive tertiary pediatric intensive care admissions (January 2004 to
December 2014) in a single center. The relationship between admission Pao2 and
crude and standardized mortality was explored using nonlinear regression.
Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to
January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases
was undertaken using the following terms: "hyperoxia," "hypoxia," "critically ill
children," "pediatric intensive care," "mortality," and/or "survival." SETTING:
Tertiary PICU. PATIENTS: Patients younger than 18 years of age. INTERVENTIONS:
The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, < 60
torr [8 kPa] or peripheral oxygen saturations, < 90%) to mortality in critically
ill children was explored. MEASUREMENTS AND MAIN RESULTS: Cohort study: Of 14,321
admissions, 7,410 children had recorded PaO2 and FIO2 at admission. Crude
mortality was 7.4% (555/7,410). This varied with admission PaO2 from 15.4%
(204/1,324) in the hypoxia group (< 8 kPa) to 5.3% (287/5,385) with normoxia and
9.1% (64/701) in the hyperoxic group (> 40 kPa). Nonlinear regression displayed a
"U-shaped" relationship between PaO2 and crude and case-mix adjusted mortality.
Systematic review: Fourteen studies and one conference abstract were eligible for
inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio
for death, of 3.13 (95% CI, 1.79-5.48; p < 0.001) compared to normoxia. Six
studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality
compared to normoxia (odds ratio, 1.15; 95% CI, 0.42-3.17; p = 0.77).
CONCLUSIONS: Hypoxia at admission is associated with increased mortality in
critically ill children, whereas the association with hyperoxia is less clear.
The cohort study demonstrated a U-shaped association between admission PaO2 and
mortality. Further examination is needed to explore the effect of hyperoxia upon
mortality prediction accuracy.
PMID- 27509364
TI - Stroke in Acquired and Congenital Heart Disease Patients and Its Relationship to
Hospital Mortality and Lasting Neurologic Deficits.
AB - OBJECTIVE: To describe strokes in patients with acquired or congenital heart
disease and investigate risk factors for in-hospital mortality and ongoing
neurologic deficits. DESIGN: Single-center, retrospective review of cardiac,
neurologic, and radiologic patient databases. SETTING: Tertiary care children's
hospital. PATIENTS: All patients with acquired or congenital heart disease
admitted from January 2010 to October 2014 identified with stroke. INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: Eighty-four stroke events were identified in
83 patients (median age, 5.9 mo; interquartile range, 0.8-33.4). Thirty-two
patients (38%) had single ventricle congenital heart disease. Eight patients (9%)
presented with symptoms at home, and the remainder was diagnosed while already
admitted to the hospital. Forty patients (48%) presented with clinically evident
neurologic deficits (e.g., weakness, seizures). Fifty-eight patients (69%) had
arterial ischemic strokes, and 13 (15%) had parenchymal hemorrhages. At
diagnosis, 54 patients (64%) were on inotropes. Twenty-nine patients (35%) had
greater than or equal to 3 cardiac procedures during their hospitalization before
stroke diagnosis. In-hospital mortality occurred in 28 patients (33%). Under
multivariate analysis, inotropes, number of cardiac procedures, lack of seizure,
and parenchymal hemorrhage were independently associated with in-hospital
mortality (p < 0.05). Fifty-four percent of survivors with neurologic follow-up
had ongoing neurologic deficits attributable to strokes (median follow-up, 15.3
mo; interquartile range, 7.0-29.9). With multivariate analysis, longer hospital
stay (p = 0.02) was independently associated with ongoing deficits. CONCLUSIONS:
A majority of patients with acquired or congenital heart disease who suffer
stroke present while hospitalized and without focal neurologic findings. In
hospital mortality is associated with inotropes, cardiac procedures, lack of
seizure, and parenchymal hemorrhage. The majority of survivors have lasting
neurologic deficits associated with longer hospital stay.
PMID- 27509365
TI - Atrophy and structural covariance of the cholinergic basal forebrain in primary
progressive aphasia.
AB - Primary progressive aphasia (PPA) is characterized by profound destruction of
cortical language areas. Anatomical studies suggest an involvement of cholinergic
basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus
subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and
structural covariance as a proxy of structural connectivity of BF nuclei in PPA
variants. We studied 62 prospectively recruited cases with the clinical diagnosis
of PPA and 31 healthy older control participants from the cohort study of the
German consortium for frontotemporal lobar degeneration (FTLD). We determined
cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI)
scans. Patterns of structural covariance of BF with cortical regions were
determined using voxel-based partial least square analysis. We found significant
atrophy of total BF and BF subregions in PPA patients compared with controls
[F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the
posterior BF, and most severe in the semantic variant and the nonfluent variant
of PPA. Structural covariance analysis in healthy controls revealed associations
of the BF nuclei, particularly the NSP, with left hemispheric predominant
prefrontal, lateral temporal, and parietal cortical areas, including Broca's
speech area (p < .001, permutation test). In contrast, the PPA patients showed
preserved structural covariance of the BF nuclei mostly with right but not with
left hemispheric cortical areas (p < .001, permutation test). Our findings agree
with the neuroanatomically proposed involvement of the cholinergic BF,
particularly the NSP, in PPA syndromes. We found a shift from a structural
covariance of the BF with left hemispheric cortical areas in healthy aging
towards right hemispheric cortical areas in PPA, possibly reflecting a
consequence of the profound and early destruction of cortical language areas in
PPA.
PMID- 27509366
TI - Glial ionic excitability: The role for sodium.
PMID- 27509367
TI - The VCU Pressure Ulcer Summit: The Search for a Clearer Understanding and More
Precise Clinical Definition of the Unavoidable Pressure Injury.
AB - This article reports the findings of the Unavoidable Pressure Ulcer Committee (of
the VCU Pressure Ulcer Summit) that was tasked with addressing key issues
associated with pressure injuries that are unavoidable or unpreventable. Our
goals were (1) to clarify nomenclature and descriptions surrounding "terminal
ulceration," (2) to describe the medical complications and comorbid conditions
that can lead to skin failure and/or terminal ulceration, (3) to describe the
variable possible causes of unavoidable pressure injuries, and (4) to present
clinical cases to exemplify pressure injuries considered to be unavoidable.
PMID- 27509368
TI - Malaria Incidence Rates from Time Series of 2-Wave Panel Surveys.
AB - Methodology to estimate malaria incidence rates from a commonly occurring form of
interval-censored longitudinal parasitological data-specifically, 2-wave panel
data-was first proposed 40 years ago based on the theory of continuous-time
homogeneous Markov Chains. Assumptions of the methodology were suitable for
settings with high malaria transmission in the absence of control measures, but
are violated in areas experiencing fast decline or that have achieved very low
transmission. No further developments that can accommodate such violations have
been put forth since then. We extend previous work and propose a new methodology
to estimate malaria incidence rates from 2-wave panel data, utilizing the class
of 2-component mixtures of continuous-time Markov chains, representing two sub
populations with distinct behavior/attitude towards malaria prevention and
treatment. Model identification, or even partial identification, requires context
specific a priori constraints on parameters. The method can be applied to
scenarios of any transmission intensity. We provide an application utilizing data
from Dar es Salaam, an area that experienced steady decline in malaria over
almost five years after a larviciding intervention. We conducted sensitivity
analysis to account for possible sampling variation in input data and model
assumptions/parameters, and we considered differences in estimates due to
submicroscopic infections. Results showed that, assuming defensible a priori
constraints on model parameters, most of the uncertainty in the estimated
incidence rates was due to sampling variation, not to partial identifiability of
the mixture model for the case at hand. Differences between microscopy- and PCR
based rates depend on the transmission intensity. Leveraging on a method to
estimate incidence rates from 2-wave panel data under any transmission intensity,
and from the increasing availability of such data, there is an opportunity to
foster further methodological developments, particularly focused on partial
identifiability and the diversity of a priori parameter constraints associated
with different human-ecosystem interfaces. As a consequence there can be more
nuanced planning and evaluation of malaria control programs than heretofore.
PMID- 27509369
TI - Diagnostic Ureteroscopy for Upper Tract Urothelial Carcinoma is Independently
Associated with Intravesical Recurrence after Radical Nephroureterectomy.
AB - PURPOSE: To determine the effect of diagnostic ureteroscopy on intravesical
recurrence in patients with upper tract urothelial carcinoma (UTUC) after radical
nephroureterec!tomy (RNU). MATERIALS AND METHODS: We conducted a retrospective
analysis of 664 patients who were treated with RNU for UTUC from June 2000 to
December 2011, excluding those who had concomitant/prior bladder tumors. Of the
664 patients, 81 underwent di!agnostic ureteroscopy (URS). We analyzed the impact
of diagnostic ureteroscopy on intravesical recurrence (IVR) using the Kaplan
Meier method. Univariate and multi!variate analyses were used to determine the
independent risk factors. RESULTS: The median follow-up time was 48 months
(interquartile range (IQR): 31- 77 months). Patients who underwent ureteroscopy
were more likely to have a small (p<0.01), early-staged (p=0.019), multifocality
(p=0.035) and ureteral tumor (p<0.001). IVR occurred in 223 patients during
follow-up within a median of 17 months (IQR: 7-33). Patients without preoperative
ureteroscopy have a statistically significant better 2-year (79.3%+/-0.02 versus
71.4%+/-0.02, p<0.001) and 5-year intravesical recurrence-free survival rates
(64.9%+/-0.05 versus 44.3%+/-0.06, p<0.001) than patients who un!derwent
ureteroscopy. In multivariate analysis, the diagnostic ureteroscopy (p=0.006),
multiple tumors (p=0.001), tumor size <3cm (p=0.008), low-grade (p=0.022) and pN0
stage tumor (p=0.045) were independent predictors of IVR. CONCLUSIONS: Diagnostic
ureteroscopy is independently associated with intravesical re!currence after
radical nephroureterectomy.
PMID- 27509370
TI - Unilateral absence of vas deferens: prevalence among 23.013 men seeking
vasectomy.
AB - PURPOSE: To determine the prevalence of unilateral absence of vas deferens (UAVD)
in men with both testes seeking vasectomy. MATERIALS AND METHODS: Computerized
charts of 23.013 patients encountered between January 1994 and December 2013 in
one university hospital and two community clinics of Quebec City, Canada, were
searched. Pre-vasectomy consultation, operative reports and semen analysis
results were reviewed to identify cases of UAVD. Cases were categorized as
confirmed (unilateral vasectomy and success confirmed by semen analysis) or
possible congenital UAVD further sub-categorized according to whether or not a
scrotal anomaly was present. RESULTS: Among 159 men identified as potentially
having UAVD, chart review revealed that 47 had only one testicle, 26 had
bilateral vasa, and four were misdiagnosed (post-vasectomy semen analysis [PVSA]
showing motile sperm after unilateral vasectomy) leaving 82 men deemed cases of
UAVD (0.36%, 95% confidence interval 0.28% to 0.43%). These were classified as
confirmed (n=48, 0.21%) and possible (n=34, 0.15%; 22 without and 12 with scrotal
anomalies) congenital UAVD. The misdiagnosis ratio of UAVD was low when scrotal
content was otherwise normal (1:48), but higher if anomalies were present (3:12).
CONCLUSIONS: Most surgeons who perform vasectomy will encounter cases of UAVD. In
most suspected cases, it is safe and effective to proceed with unilateral
vasectomy under local anesthesia while stressing the need for PVSA. Further
studies or scrotal exploration may be considered in patient with prior scrotal
surgery.
PMID- 27509371
TI - Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: A
contemporary evaluation.
AB - INTRODUCTION: Hemorrhagic cystitis (HC) represents a challenging clinical entity.
While various intravesical agents have been utilized in this setting, limited
data exist regard!ing safety or efficacy. Herein, then, we evaluated the
effectiveness and complications associated with intravesical alum instillation
for HC in a contemporary cohort. MATERIALS AND METHODS: We identified 40 patients
treated with intravesical alum for HC between 1997-2014. All patients had failed
previous continuous bladder irrigation with normal saline and clot evacuation.
Treatment success was defined as requiring no additional therapy beyond normal
saline irrigation after alum instillation. RESULTS: Median patient age was 76.5
years (IQR 69, 83). Pelvic radiation was the most common etiology for HC (n=38,
95%). Alum use decreased patient's transfusion requirement, with 82% (32/39)
receiving a transfusion within 30 days before alum instillation (median 4 units)
versus 59% (23/39) within 30 days after completing alum (median 3 units)
(p=0.05). In total, 24 patients (60%) required no additional therapy prior to
hospital discharge. Moreover, at a median follow-up of 17 months (IQR 5, 38.5),
13 patients (32.5%) remained without additional treatment for HC. Adverse
ef!fects were reported in 15 patients (38%), with bladder spasms representing the
most common event (14/40; 35%). No clinical evidence of clinically significant
systemic absorption was detected. CONCLUSION: Intravesical alum therapy is well
tolerated, with resolution of HC in ap!proximately 60% of patients, and a durable
response in approximately one-third. Given its favorable safety/efficacy profile,
intravesical alum may be considered as a first-line treatment option for patients
with HC.
PMID- 27509372
TI - External validation of EORTC risk scores to predict recurrence after
transurethral resection of brazilian patients with non -muscle invasive bladder
cancer stages Ta and T1.
AB - : Validate the EORTC risk tables in Brazilian patients with NMIBC. METHODS: 205
patients were analyzed. The 6 parameters analyzed were: histologic grading,
pathologic stage, size and number of tumors, previous recurrence rate and
concomitant CIS. The time for first recurrence (TFR), risk score and probability
of re!currence were calculated and compared to the probabilities obtained from
EORTC risk tables. C-index was calculated and accuracy of EORTC tables was
analyzed. RESULTS: pTa was presented in 91 (44.4%) patients and pT1 in 114
(55.6%). Ninety-seven (47.3%) patients had solitary tumor, and 108 (52.7%)
multiple tumors. One hundred and three (50.2%) patients had tumors smaller than 3
cm and 102 (40.8%) had bigger than 3 cm. Concomitant CIS was observed in 21
(10.2%) patients. Low grade was presented in 95 (46.3%) patients, and high grade
in 110 (53.7%). Intravesical therapy was utilized in 105 (56.1%) patients.
Recurrence was observed in 117 (57.1%) patients and the mean TFR was 14,2 +/- 7,3
months. C-index was 0,72 for 1 year and 0,7 for 5 years. The re!currence risk was
28,8% in 1 year and 57,1% in 5 years, independently of the scoring risk. In our
population, the EORTC risk tables overestimated the risk of recurrence in 1 year
and underestimated in 5 years. CONCLUSION: The validation of the EORTC risk
tables in Brazilian patients with NMIBC was satisfactory and should be stimulated
to predict recurrence, although these may overestimated the risk of recurrence in
1 year and underestimated in 5 years.
PMID- 27509373
TI - Minimally invasive percutaneous nephrolithotomy guided by ultrasonography to
treat upper urinary tract calculi complicated with severe spinal deformity.
AB - OBJECTIVE: To report our experience of minimally invasive percutaneous
nephrolithotomy(MPCNL) in managing upper urinary tract calculi complicated with
severe spinal deformity. MATERIALS AND METHODS: Between August 2001 to December
2012, 16 upper urinary calculi in 13 patients with severe spinal deformity were
treated by MPCNL. Preoperative investigation of the respiratory function,
evaluation of anatomy by intravenous uro!graphy (IVU) and CT scan, and
preoperative kidney ultrasonagraphy with simulation of the percutaneous puncture
were performed in all patients. The percutaneous puncture was guided by
ultrasonography. RESULTS: A total of 19 MPCNL procedures were performed in 16
kidneys, with an ave!rage 1.2 procedures in each kidney. Three kidneys needed two
sessions of MPCNL, and 2 kidneys needed combined treatment with retrograde
flexible ureterscopic lithotripsy. All procedures were successfully completed
with no major complications during or after surgery. The mean (range) operative
duration was 67 (20-150) min and the mean postoperative haemoglobin drop was 1.0
(0.2-3.1) g/dL. Complete stone-free status was achieved in 14 kidneys. At a mean
follow-up of 48(3-86) months, recurrence of small lower calyx stone was detected
in one patient. Recurrent UTI was documented by urine culture in two patients and
managed with sensitive antibiotics. CONCLUSION: PCNL for patients with severe
spinal deformities is challenging. Ultra!sonography-assisted puncture can allow
safe and successfully establishment of PCN tract through a narrow safety margin
of puncture and avoid the injury to the adjacent organs. However, the operation
should be performed in tertiary centers with significant expertise in managing
complex urolithiasis.
PMID- 27509374
TI - Sexual Health Matters: Management of Female Sexual Dysfunction.
PMID- 27509375
TI - Diminished Phosphorylation of CREB Is a Key Event in the Dysregulation of
Gluconeogenesis and Glycogenolysis in PCB126 Hepatotoxicity.
AB - The dioxin-like PCB126 elicits toxicity in various target organs. In rat liver,
an alteration in the transcript levels of several genes involved in glucose and
fatty acid metabolism provides insights into the origin of its hepatotoxicity. To
explore the mechanisms, male Sprague-Dawley rats, fed an AIN-93G diet, were
injected with PCB126 (1 or 5 MUmol/kg) or corn oil and euthanized after 2 weeks.
PCB126 significantly decreased serum glucose levels and the transcript levels of
genes of many gluconeogenic and glycogenolytic enzymes under the transcriptional
control of a nuclear transcription factor, cAMP response element-binding protein
(CREB). As a novel finding, we show that PCB126 significantly decreases CREB
phosphorylation, which is important for regulating both gluconeogenesis and fatty
acid oxidation in the liver and explains CREB's integrative effects on both
carbohydrate and lipid metabolism in PCB126 toxicity.
PMID- 27509378
TI - Acute Lymphoblastic Leukemia Presenting With Pancytopenia Followed by a 14-Month
Long Period of Transient Remission Possibly Supporting the Adrenal Hypothesis of
Leukemogenesis.
AB - A small group of children with acute lymphoblastic leukemia (ALL) have a
preleukemic phase of pancytopenia followed by a period of spontaneous remission
before the diagnosis (pre-ALL). A 6-year-old girl presented with pancytopenia,
fever, and myelodysplasia. Following transient remission pre-B ALL was diagnosed
14 months later. Clonal B-lineage blasts at the period of pancytopenia were
identified retrospectively. The interval between pre-ALL and ALL-diagnosis was
longer than previously reported. The infection was clinically severe and might
have induced a significant endogenous corticosteroids production resulting in the
long-lasting remission. The case supports the adrenal and the Coley's toxin
hypothesis in leukemogenesis.
PMID- 27509377
TI - Intensive treatment and survival outcomes in NUT midline carcinoma of the head
and neck.
AB - BACKGROUND: NUT midline carcinoma is a rare and aggressive genetically
characterized subtype of squamous cell carcinoma frequently arising from the head
and neck. The characteristics and optimal management of head and neck NUT midline
carcinoma (HNNMC) are unclear. METHODS: A retrospective review of all known cases
of HNNMC in the International NUT Midline Carcinoma Registry as of December 31,
2014, was performed. Forty-eight consecutive patients were treated from 1993 to
2014, and clinicopathologic variables and outcomes for 40 patients were available
for analyses; they composed the largest HNNMC cohort studied to date. Overall
survival (OS) and progression-free survival (PFS) according to patient
characteristics and treatment were analyzed. RESULTS: This study identified a 5
fold increase in the diagnosis of HNNMC from 2011 to 2014. The median age was
21.9 years (range, 0.1-81.7 years); the male and female proportions were 40% and
60%, respectively; and 86% had bromodomain containing 4-nuclear protein in testis
(BRD4-NUT) fusion. The initial treatment was initial surgery with or without
adjuvant chemoradiation or adjuvant radiation (56%), initial radiation with or
without chemotherapy (15%), or initial chemotherapy with or without surgery or
radiation (28%). The median PFS was 6.6 months (range, 4.7-8.4 months). The
median OS was 9.7 months (range, 6.6-15.6 months). The 2-year PFS rate was 26%
(95% confidence interval [CI], 13%-40%). The 2-year OS rate was 30% (95% CI, 16%
46%). Initial surgery with or without postoperative chemoradiation or radiation
(P = .04) and complete resection with negative margins (P = .01) were significant
predictors of improved OS even after adjustments for age, tumor size, and neck
lymphadenopathy. Initial radiation or chemotherapy and the NUT translocation type
were not associated with outcomes. CONCLUSIONS: HNNMC portends a poor prognosis.
Aggressive initial surgical resection with or without postoperative
chemoradiation or radiation is associated with significantly enhanced survival.
Chemotherapy or radiation alone is often inadequate. Cancer 2016;122:3632-40. (c)
2016 American Cancer Society.
PMID- 27509379
TI - Transfusion Therapy in Children With Sickle Cell Disease.
AB - Hydroxyurea, blood transfusions, and hematopoietic stem cell transplantation
represent the 3 disease-modifying therapies in children with sickle cell disease
(SCD). Blood transfusions play an increasingly important role in both prevention
and management of SCD complications in this age group. This review will focus on
the indications of blood transfusion in children with SCD and modalities of its
administration. It will also highlight the complications of this life-saving
therapy and ways of optimizing transfusion to minimize its associated risks.
PMID- 27509380
TI - Progressive Rod-Cone Degeneration (PRCD) Protein Requires N-Terminal S-Acylation
and Rhodopsin Binding for Photoreceptor Outer Segment Localization and
Maintaining Intracellular Stability.
AB - The light-sensing outer segments of photoreceptor cells harbor hundreds of
flattened membranous discs containing the visual pigment, rhodopsin, and all the
proteins necessary for visual signal transduction. PRCD (progressive rod-cone
degeneration) protein is one of a few proteins residing specifically in
photoreceptor discs, and the only one with completely unknown function. The
importance of PRCD is highlighted by its mutations that cause photoreceptor
degeneration and blindness in canine and human patients. Here we report that PRCD
is S-acylated at its N-terminal cysteine and anchored to the cytosolic surface of
disc membranes. We also showed that mutating the S-acylated cysteine to tyrosine,
a common cause of blindness in dogs and a mutation found in affected human
families, causes PRCD to be completely mislocalized from the photoreceptor outer
segment. We next undertook a proteomic search for PRCD-interacting partners in
disc membranes and found that it binds rhodopsin. This interaction was confirmed
by reciprocal precipitation and co-chromatography experiments. We further
demonstrated this interaction to be critically important for supporting the
intracellular stability of PRCD, as the knockout of rhodopsin caused a drastic
reduction in the photoreceptor content of PRCD. These data reveal the cause of
photoreceptor disease in PRCD mutant dogs and implicate rhodopsin to be involved
in PRCD's unknown yet essential function in photoreceptors.
PMID- 27509381
TI - Seasonal and Species Variation of the Hepatotoxin Indospicine in Australian
Indigofera Legumes As Measured by UPLC-MS/MS.
AB - Livestock industries have maintained a keen interest in pasture legumes because
of the high protein content and nutritive value. Leguminous Indigofera plant
species have been considered as having high feeding values to be utilized as
pasture, but the occurrence of the toxic constituent indospicine in some species
has restricted this utility. Indospicine has caused both primary and secondary
hepatotoxicosis and also reproductive losses, but has only previously been
determined in a small number of Indigofera species. This paper validates a high
throughput ultraperformance liquid chromatography-tandem mass spectrometry (UPLC
MS/MS) method to determine the indospicine content of various Indigofera species
found in Australian pasture. Twelve species of Indigofera together with
Indigastrum parviflorum plants were collected and analyzed. Of the 84 samples
analyzed, *I. spicata (the asterisk indicates a naturalized species) contained
the highest indospicine level (1003 +/- 328 mg/kg DM, n = 4) followed by I.
linnaei (755 +/- 490 mg/kg DM, n = 51). Indospicine was not detected in 9 of the
remaining 11 species and at only low levels (<10 mg/kg DM) in 2 of 8 I. colutea
specimens and in 1 of 5 I. linifolia specimens. Indospicine concentrations were
below quantitation levels for other Indigofera spp. (I. adesmiifolia, I. georgei,
I. hirsuta, I. leucotricha, *I. oblongifolia, I. australis, and I. trita) and
Indigastrum parviflorum. One of the more significant findings to emerge from this
study is that the indospicine content of I. linnaei is highly variable (from 159
to 2128 mg/kg DM, n = 51) and differs across both regions and seasons. Its first
regrowth after spring rain has a higher (p < 0.01) indospicine content than
growth following more substantial summer rain. The species collected include the
predominant Indigofera in Australia pasture, and of these, only *I. spicata and
I. linnaei contain high enough levels of indospicine to pose a potential toxic
threat to grazing herbivores.
PMID- 27509382
TI - DIETARY SILVER NANOPARTICLES REDUCE FITNESS IN A BENEFICIAL, BUT NOT PEST, INSECT
SPECIES.
AB - Silver nanoparticles (AgNPs) have antimicrobial and insecticidal properties and
they have been considered for their potential use as insecticides. While they do,
indeed, kill some insects, two broader issues have not been considered in a
critical way. First, reports of insect-lethal AgNPs are often based on simplistic
methods that yield nanoparticles of nonuniform shapes and sizes, leaving
questions about the precise treatments test insects experienced. Second, we do
not know how AgNPs influence beneficial insects. This work addresses these
issues. We assessed the influence of AgNPs on life history parameters of two
agricultural pest insect species, Heliothis virescens (tobacco budworm) and
Trichoplusia ni (cabbage looper) and a beneficial predatory insect species,
Podisus maculiventris (spined soldier bug), all of which act in agroecosystems.
Rearing the two pest species on standard media amended with AgNPs led to
negligible influence on developmental times, pupal weights, and adult emergence,
however, they led to retarded development, reductions in adult weight and
fecundity, and increased mortality in the predator. These negative effects on the
beneficial species, if also true for other beneficial insect species, would have
substantial negative implications for continued development of AgNPs for insect
pest management programs.
PMID- 27509383
TI - Effects of waterborne Cu exposure on intestinal copper transport and lipid
metabolism of Synechogobius hasta.
AB - The present study was conducted to explore the effects of waterborne Cu exposure
on intestinal Cu transport and lipid metabolism of Synechogobius hasta. S. hasta
were exposed to 0, 0.4721 and 0.9442MUM Cu, respectively. Sampling occurred on
days 0, 21 and 42, respectively. Growth performance, intestinal lipid deposition,
Cu content, and activities and mRNA expression of enzymes and genes involved in
Cu transport and lipid metabolism were analyzed. Cu exposure decreased WG and SGR
on days 21 and 42. Cu exposure increased intestinal Cu and lipid contents.
Increased Cu accumulation was attributable to increased enzymatic activities (Cu
ATPase and Cu, Zn-SOD) and genes' (CTR1, CTR2, DMT1, ATP7a, ATP7b, MT1 and MT2)
expression involved in Cu transport. Waterborne Cu exposure also increased
activities of lipogenic enzymes (6PGD and ICDH on both days 21 and 42, ME on day
42), up-regulated mRNA levels of lipogenic genes (G6PD, 6PGD, ME, ICDH, FAS and
ACCa), lipolytic genes (ACCb, CPT I and HSLa) and genes involved in intestinal
fatty acid uptake (IFABP and FATP4) on both days 21 and 42. The up-regulation of
lipolysis may result from the increased metabolic expenditure for detoxification
and maintenance of the normal body functions in a response to Cu exposure.
Meantime, Cu exposure increased lipogenesis and fatty acid uptake, leading to net
lipid accumulation in the intestine despite increased lipolysis. To our
knowledge, this is the first report involved in intestinal lipid metabolism in
combination with intestinal Cu absorption following waterborne Cu exposure, which
provides new insights and evidence into Cu toxicity in fish.
PMID- 27509384
TI - Probing the Interstate Coupling near a Conical Intersection by Optical
Spectroscopy.
AB - Conical intersections are points where adiabatic potential energy surfaces cross.
The interstate coupling between the potential energy surfaces plays a crucial
role in many processes associated with conical intersections. Still no method
exists to measure this coupling driving the chemical reactions between the
potential energy surfaces involved. In this Letter, using a generic model for
photoisomerization, we propose a novel experimental approach to estimate the
coupling that mixes the electronic states near a conical intersection. The
approach is based on analyzing the vibrational wavepacket of the reactant in the
adiabatic ground and excited electronic states. The nuclear wavepacket dynamics
are extracted from linear absorption and two-dimensional electronic spectroscopy.
Comparing the frequencies of the coupling mode in the adiabatic ground and
excited states from models with and without coupling between the potential energy
surfaces suggests an experimental tool to determine the interstate coupling.
PMID- 27509386
TI - Targeted Consent for Research on Standard of Care Interventions in the Emergency
Setting.
AB - OBJECTIVES: There has been significant debate over what consent process, if any,
should be used for clinical trials that compare two or more interventions within
the standard of care. Some claim that all clinical trials should obtain in-depth
research consent because they use subjects to obtain data for the benefit of
future patients. Others argue that clinical trials that are limited to
interventions within the standard of care do not need to obtain research consent
at all. Settling this debate is especially challenging in the emergency setting.
The potential for significant morbidity and mortality provides a strong reason to
obtain research consent for standard-of-care trials in the emergency setting.
Yet, the emergency setting also introduces significant barriers to traditional in
depth research consent. The present article considers to what extent a targeted
consent process can resolve these tensions. DATA SYNTHESIS: We first identified
the ethical goals that are promoted by obtaining consent for standard-of-care
research and the barriers to obtaining consent that arise in the emergency
setting. We then evaluated whether, despite the barriers, it is possible to
develop a targeted consent process that promotes the goals for consent in the
context of standard-of-care trials. CONCLUSIONS: Targeted consent offers an
ethically appropriate way to obtain consent for many standard-of-care trials in
the emergency setting. For studies subject to U.S. regulations, and those subject
to other regulations that include similar consent requirements, targeted
consent's verbal disclosure and written form provide a way to satisfy research
regulations without blocking valuable studies. For trials that qualify for a
waiver of the consent requirements, targeted consent's verbal disclosure is
preferable to waiving consent, provided a slight delay is consistent with
appropriate care, and there is a capacitated patient or surrogate available.
PMID- 27509387
TI - Errors, Omissions, and Outliers in Hourly Vital Signs Measurements in Intensive
Care.
AB - OBJECTIVE: To empirically examine the prevalence of errors, omissions, and
outliers in hourly vital signs recorded in the ICU. DESIGN: Retrospective
analysis of vital signs measurements from a large-scale clinical data warehouse
(Multiparameter Intelligent Monitoring in Intensive Care III). SETTING: Data were
collected from the medical, surgical, cardiac, and cardiac surgery ICUs of a
tertiary medical center in the United States. PATIENTS: We analyzed data from
approximately 48,000 ICU stays including approximately 28 million vital signs
measurements. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used the
vital sign day as our unit of measurement, defined as all the recordings from a
single patient for a specific vital sign over a single 24-hour period.
Approximately 30-40% of vital sign days included at least one gap of greater than
70 minutes between measurements. Between 3% and 10% of blood pressure
measurements included logical inconsistencies. With the exception of pulse
oximetry vital sign days, the readings in most vital sign days were normally
distributed. We found that 15-38% of vital sign days contained at least one
statistical outlier, of which 6-19% occurred simultaneously with outliers in
other vital signs. CONCLUSIONS: We found a significant number of missing,
erroneous, and outlying vital signs measurements in a large ICU database. Our
results provide empirical evidence of the nonrepresentativeness of hourly vital
signs. Additional studies should focus on determining optimal sampling
frequencies for recording vital signs in the ICU.
PMID- 27509388
TI - Hospital Volume and Outcomes of Noninvasive Ventilation in Patients Hospitalized
With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease.
AB - OBJECTIVE: To determine the relationship between hospital noninvasive ventilation
caseload and outcomes among patients with an acute chronic obstructive pulmonary
disease exacerbation. DESIGN: Cross-sectional study of 13,893 patients with
chronic obstructive pulmonary disease treated with noninvasive ventilation.
SETTING: A total of 243 U.S. hospitals participating in the Premier Inpatient
Database. PATIENTS: A total of 13,893 patients admitted between July 2009 and
June 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Annual hospital
volume of noninvasive ventilation was analyzed as a continuous variable, as well
as after grouping it in four categories. The median hospital annual volume of
noninvasive ventilation use was 627 and varied from 234 admissions in quartile 1
to 1,529 admissions in quartile 4. Noninvasive ventilation failure occurred in
15.2%, and in-hospital mortality was 6.5%. After adjusting for patient
characteristics, relative to low-volume hospitals, high-volume hospitals did not
have lower noninvasive ventilation failure (odds ratio quartile 4 vs quartile 1,
1.05; 95% CI, 0.65-1.68) or in-hospital mortality (odds ratio quartile 4 vs
quartile 1, 0.88; 95% CI, 0.69-1.12). In a hierarchical multivariable analysis
with adjustment for patient characteristics where volume was assessed as a
continuous variable, hospital volume was not related to outcomes, including
noninvasive ventilation failure (p = 0.87), in-hospital mortality (p = 0.88), 30
day readmission for chronic obstructive pulmonary disease (p = 0.83), or hospital
length of stay (p = 0.12). CONCLUSIONS: The results of this large retrospective
cohort study suggest that hospitals with higher noninvasive ventilation volume do
not achieve better outcomes of patients with chronic obstructive pulmonary
disease exacerbation treated with noninvasive ventilation; even hospitals with
low noninvasive ventilation volume are able to successfully implement this
intervention.
PMID- 27509389
TI - The Postcardiac Arrest Consult Team: Impact on Hospital Care Processes for Out-of
Hospital Cardiac Arrest Patients.
AB - OBJECTIVE: To evaluate whether a Post-Arrest Consult Team improved care and
outcomes for patients with out-of-hospital cardiac arrest. DESIGN: Prospective
cohort study of Post-Arrest Consult Team implementation at two hospitals, with
concurrent controls from 27 others. SETTING: Twenty-nine hospitals within the
Strategies for Post-Arrest Care Network of Southern Ontario, Canada. PATIENTS: We
included comatose adult nontraumatic out-of-hospital cardiac arrest patients
surviving more than or equal to 6 hours after emergency department arrival who
had no contraindications to targeted temperature management. INTERVENTION: The
Post-Arrest Consult Team was an advisory consult service to improve 1) targeted
temperature management, 2) assessment for percutaneous coronary intervention, 3)
electrophysiology assessment, and 4) appropriately delayed neuroprognostication.
MEASUREMENTS AND MAIN RESULTS: We used generalized linear mixed models to explore
the association between Post-Arrest Consult Team implementation and performance
of targeted processes. We included 1,006 patients. The Post-Arrest Consult Team
was associated with a significant reduction over time in rates of withdrawal of
life-sustaining therapy within 72 hours of emergency department arrival on the
basis of predictions of poor neurologic prognosis (ratio of odds ratios, 0.13;
95% CI, 0.02-0.98). Post-Arrest Consult Team was not associated with improved
successful targeted temperature management (ratio of odds ratios, 0.91; 95% CI,
0.31-2.65), undergoing angiography (ratio of odds ratios, 1.91; 95% CI, 0.17
21.04), receiving electrophysiology consultation (ratio of odds ratios, 0.93; 95%
CI, 0.11-8.16), or functional survival (ratio of odds ratios, 0.75; 95% CI, 0.19
2.94). CONCLUSIONS: Implementation of a Post-Arrest Consult Team reduced
premature withdrawal of life-sustaining therapy but did not improve rates of
successful targeted temperature management, coronary angiography, formal
electrophysiology assessments, or functional survival for comatose patients after
out-of-hospital cardiac arrest.
PMID- 27509391
TI - The Impact of Interventions to Improve Sleep on Delirium in the ICU: A Systematic
Review and Research Framework.
AB - OBJECTIVE: This study aimed to assess whether interventions targeted at improving
sleep in the ICU were associated with reductions in ICU delirium. Secondary
outcomes include duration of delirium and ICU length of stay. DATA SOURCES:
MEDLINE, CINAHL, Web of Science, Scopus, WorldCat, and International
Pharmaceutical Abstracts were searched from inception to January 2016. STUDY
SELECTION: Studies investigating any type of sleep intervention (nonpharmacologic
or pharmacologic) and assessing the impact on ICU delirium were included. Any
type of study design was permitted so long as the delirium assessment was made at
least daily with a validated delirium assessment tool. DATA EXTRACTION: The
following data were extracted: first author, year of publication, study design,
ICU type, components of sleep intervention, use of sleep assessment tool, patient
age, sex, severity of illness, sleep measures, delirium assessment tool,
incidence of delirium, duration of delirium, and ICU length of stay. The
incidence of delirium was used to compare rates of ICU delirium across studies.
Methodologic quality of included studies was evaluated using the Effective Public
Health Practice Project quality assessment tool. DATA SYNTHESIS: Of 488 citations
screened, 10 studies were identified for inclusion in the final review; six of
which demonstrated a statistically significant reduction in the incidence of ICU
delirium associated with sleep intervention. Four studies assessed duration of
delirium; of which, three reported a shorter duration of delirium with sleep
intervention. Two studies associated sleep intervention with a reduced ICU length
of stay. In regard to quality assessment and risk of bias, only one study was
assessed as strong. Multiple identified confounders and the significant
qualitative assessment of heterogeneity limit both the conclusions that can be
drawn from these findings and the quantitative pooling of data. CONCLUSIONS:
Although sleep interventions seem to be a promising approach for improving
delirium-related outcomes, studies are limited by bias issues, varying
methodologies, and multiple confounders, making the evidence base for this
conclusion limited at best. Future studies would benefit from a systematic
approach to studying the link between sleep intervention and delirium-related
outcomes, which is outlined in the context of reviewing the existing literature.
PMID- 27509390
TI - Double-Stranded RNA Interacts With Toll-Like Receptor 3 in Driving the Acute
Inflammatory Response Following Lung Contusion.
AB - OBJECTIVES: Lung contusion is a major risk factor for the development of acute
respiratory distress syndrome. We set to determine the role of toll-like receptor
3 and the binding of double-stranded RNA in the pathogenesis of sterile injury
following lung contusion. DESIGN: Toll-like receptor 3 expression was analyzed in
postmortem lung samples from patients with lung contusion. Unilateral lung
contusion was induced in toll-like receptor 3 (-/-), TIR-domain-containing
adapter-inducing interferon-beta (-/-), and wild-type mice. Subsequently, lung
injury and inflammation were evaluated. Apoptotic indices, phagocytic activity,
and phenotypic characterization of the macrophages were determined. Double
stranded RNA in bronchoalveolar lavage and serum samples following lung contusion
was measured. A toll-like receptor 3/double-stranded RNA ligand inhibitor was
injected into wild-type mice prior to lung contusion. MEASUREMENTS AND MAIN
RESULTS: Toll-like receptor 3 expression was higher in patients and wild-type
mice with lung contusion. The degree of lung injury, inflammation, and macrophage
apoptosis was reduced in toll-like receptor 3 (-/-), TIR-domain-containing
adapter-inducing interferon-beta (-/-), and wild-type mice with toll-like
receptor 3 antibody neutralization. Alveolar macrophages from toll-like receptor
3 (-/-) mice had a lower early apoptotic index, a predominant M2 phenotype and
increased surface translocation of toll-like receptor 3 from the endosome to the
surface. When compared with viral activation pathways, lung injury in lung
contusion demonstrated increased p38 mitogen-activated protein kinases,
extracellular signal-regulated kinase 1/2 phosphorylation with inflammasome
activation without a corresponding increase in nuclear factor-kappaB or type-1
interferon production. Additionally, pretreatment with toll-like receptor
3/double-stranded RNA ligand inhibitor led to a reduction in injury,
inflammation, and macrophage apoptosis. CONCLUSIONS: We conclude that the
interaction of double-stranded RNA from injured cells with toll-like receptor 3
drives the acute inflammatory response following lung contusion.
PMID- 27509385
TI - Functional Outcome Trajectories After Out-of-Hospital Pediatric Cardiac Arrest.
AB - OBJECTIVES: To analyze functional performance measures collected prospectively
during the conduct of a clinical trial that enrolled children (up to age 18 yr
old), resuscitated after out-of-hospital cardiac arrest, who were at high risk of
poor outcomes. DESIGN: Children with Glasgow Motor Scale score less than 5,
within 6 hours of resuscitation, were enrolled in a clinical trial that compared
two targeted temperature management interventions (THAPCA-OH, NCT00878644). The
primary outcome, 12-month survival with Vineland Adaptive Behavior Scale, second
edition, score greater or equal to 70, did not differ between groups. SETTING:
Thirty-eight North American PICUs. PARTICIPANTS: Two hundred ninety-five children
were enrolled; 270 of 295 had baseline Vineland Adaptive Behavior Scale, second
edition, scores greater or equal to 70; 87 of 270 survived 1 year. INTERVENTIONS:
Targeted temperatures were 33.0 degrees C and 36.8 degrees C for hypothermia and
normothermia groups. MEASUREMENTS AND MAIN RESULTS: Baseline measures included
Vineland Adaptive Behavior Scale, second edition, Pediatric Cerebral Performance
Category, and Pediatric Overall Performance Category. Pediatric Cerebral
Performance Category and Pediatric Overall Performance Category were rescored at
hospital discharges; all three were scored at 3 and 12 months. In survivors with
baseline Vineland Adaptive Behavior Scale, second edition scores greater or equal
to 70, we evaluated relationships of hospital discharge Pediatric Cerebral
Performance Category with 3- and 12-month scores and between 3- and 12-month
Vineland Adaptive Behavior Scale, second edition, scores. Hospital discharge
Pediatric Cerebral Performance Category scores strongly predicted 3- and 12-month
Pediatric Cerebral Performance Category (r = 0.82 and 0.79; p < 0.0001) and
Vineland Adaptive Behavior Scale, second edition, scores (r = -0.81 and -0.77; p
< 0.0001). Three-month Vineland Adaptive Behavior Scale, second edition, scores
strongly predicted 12-month performance (r = 0.95; p < 0.0001). Hypothermia
treatment did not alter these relationships. CONCLUSIONS: In comatose children,
with Glasgow Motor Scale score less than 5 in the initial hours after out-of
hospital cardiac arrest resuscitation, function scores at hospital discharge and
at 3 months predicted 12-month performance well in the majority of survivors.
PMID- 27509392
TI - Expression of embryonic stem cell markers in pyogenic granuloma.
AB - BACKGROUND: Recent description of hemangioblastic blood islands within pyogenic
granuloma (PG) has led us to investigate the expression of embryonic stem cell
(ESC) markers in this tumor. METHODS: In this study we examined the expression of
ESC markers, OCT4, SOX2, STAT3 and NANOG in PG samples from 11 patients, by
immunohistochemical (IHC) staining, NanoString analysis and in situ hybridization
(ISH). RESULTS: IHC staining demonstrated the expression of pSTAT3, OCT4, SOX2
and NANOG by the endothelium of the microvessels in PG whilst pSTAT3, SOX2 and
NANOG were also expressed by cells in the interstitium, outside of the
microvessels. NanoString and ISH analysis showed mRNA expression for STAT3, OCT4
and NANOG in PG. CONCLUSIONS: The expression of the ESC markers, OCT4, SOX2,
pSTAT3 and NANOG, suggests the endothelium of PG displays a primitive phenotype.
Cells in the interstitium expressing pSTAT3, SOX2 and NANOG may represent a more
downstream derivative of the primitive endothelium, or a separate population. The
primitive nature of the endothelium and cells in the interstitium reveals novel
insights into the biology of PG. To the best of our knowledge, this is the first
demonstration of the expression of ESC markers in PG, implying the presence of a
hematopoietic stem cell population.
PMID- 27509393
TI - Hydrothermal Crystallization of Uranyl Coordination Polymers Involving an
Imidazolium Dicarboxylate Ligand: Effect of pH on the Nuclearity of Uranyl
Centered Subunits.
AB - Four uranyl-bearing coordination polymers (1-4) have been hydrothermally
synthesized in the presence of the zwitterionic 1,3-bis(carboxymethyl)imidazolium
(= imdc) anion as organic linkers after reaction at 150 degrees C. At low pH
(0.8-3.1), the form 1 ((UO2)2(imdc)2(ox).3H2O; ox stands for oxalate group) has
been identified. Its crystal structure (XRD analysis) consists of the 8-fold
coordinated uranyl centers linked to each other through the imdc ligand together
with oxalate species coming from the partial decomposition of the imdc molecule.
The resulting structure is based on one-dimensional infinite ribbons intercalated
by free water molecules. By adding NaOH solution, a second form 2 is observed for
pH 1.9-3.9 but in a mixture with phase 1. The pure phase of 2 is obtained after a
hydrothermal treatment at 120 degrees C. It corresponds to a double-layered
network (UO2(imdc)2) composed of 7-fold-coordinated uranyl cations linked via the
imdc ligands. In the same pH range, a third phase ((UO2)3O2(H2O)(imdc).H2O, 3) is
formed: it is composed of hexanuclear units of 7-fold- and 8-fold-coordinated
uranyl cations, connected via the imdc molecules in a layered assembly. At higher
pH, the chain-like solid (UO2)3O(OH)3(imdc).2H2O (4) is observed and composed of
the infinite edge-sharing uranyl-centered pentagonal bipyramidal polyhedra. As a
function of pH, uranyl nuclearity increases from discrete 8- or 7-fold uranyl
centers (1, 2) to hexanuclear bricks (3) and then infinite chains in 4 (built up
from the hexameric fragments found in 3). This observation emphasized the
influence of the hydrolysis reaction occurring between uranyl centers. The
compounds have been further characterized by thermogravimetric analysis,
infrared, and luminescence spectroscopy.
PMID- 27509394
TI - Effects of Oxygen Impurities on Glass-Formation Ability in Zr2Cu Alloy.
AB - Using ab initio molecular dynamics simulations, we show that oxygen (O)
impurities have a noticeable influence on the glass-formation ability (GFA) in
Zr2Cu alloy. Cu-centered icosahedral clusters and Zr-centered Kasper polyhedra
are the dominate short-range orders in undercooled Zr2Cu liquid which are most
likely to be responsible for the glass formation in Zr2Cu systems. When O is
introduced, a Zr octahedron is formed around the O impurity. Most of the Zr atoms
in the octahedron also serve as the bridging atoms for cross-linked Kasper
polyhedral network, resulting in an O-centered medium range order (MRO)
structure. Meanwhile, Cu atoms are moved away from the first shell of O-centered
octahedral clusters. With 1 at. % O impurities, the fractions of Zr-centered
clusters are less affected, while the increase of ideal icosahedral order and
decrease of distorted icosahedral order lead to a more stable atomic structure.
This result suggests that a low concentration of O impurities would improve the
GFA in Zr2Cu alloy. However, when ~5 at. % O impurities are included, the ideal
icosahedral clusters and Zr-centered Kasper polyhedra are seriously suppressed by
the formation of O-centered MRO, which can lead to deterioration of GFA. Our
analyses provide useful insight into glass formation behavior in O-doped metallic
alloy systems.
PMID- 27509395
TI - The provision of speech-language therapy in services destined to individuals with
Autism Spectrum Disorder (ASD).
AB - The increased prevalence of autism spectrum disorder (ASD) worldwide has been a
major public health concern; therefore, discussion about the services and
therapies required has become important. This study aimed to characterize the
provision of speech-language therapy services in the metropolitan area of Sao
Paulo. To this end, a questionnaire with 23 questions was developed based on the
Balanced Scorecard methodology. This questionnaire was applied to 854 individuals
assisted in 25 ASD services. The results show that only 64% of the ASD services
offer speech-language therapy and that the number of individuals assisted is
below the expected. Therefore, there is a necessity for better management in the
speech-language therapy services offered to the ASD population.
PMID- 27509396
TI - Correlations between vocabulary and phonological acquisition: number of words
produced versus acquired consonants.
AB - PURPOSE: To verify the probable correlations between the number of word types and
the number of consonants in the general phonological system in children with
typical language development. METHODS: Study participants were 186 children aged
one year and six months to five years, 11 months and 29 days who were monolingual
Brazilian Portuguese speakers with typical language development. Data collection
involved speech, language and hearing assessments and spontaneous speech
recordings. Phonology was assessed with regard to the number of acquired
consonants in the general phonological system, in each syllable structure and in
Implicational Model of Feature Complexity (IMFC) levels. Vocabulary was assessed
with regard to number of word types produced. These data were compared across age
groups. After that, correlations between the word types produced and the
variables established for the phonological system were analyzed. The significance
level adopted was 5%. RESULTS: All phonological aspects evaluated presented
gradual growth. Word types produced showed a similar behavior, though with a
small regression at the age of five years. Different positive correlations
occurred between the spoken word types and the variables analyzed in the
phonological system. Only one negative correlation occurred with respect to the
production of complex onset in the last age group analyzed. CONCLUSION: The
phonology and vocabulary of the study participants present similar behaviors.
There are many positive correlations between the word types produced and the
different aspects of phonology, except regarding complex onset.
PMID- 27509397
TI - Effects of hearing and cognitive impairment in sentence recognition.
AB - PURPOSE: To evaluate the effects of hearing and cognitive impairment in sentence
recognition in elderly people. METHODS: The study included 30 elderly individuals
divided into two groups: GI, with 17 elderly people without hearing loss and GII,
with 13 elderly people with mild hearing loss. In order to evaluate their
cognition, the Mini Mental State Examination (MMSE) was performed, whereas, for
the evaluation of the auditory effects, the Portuguese Sentence List (PSL) was
performed, in which the sentence recognition thresholds in silence (SRTS) and the
signal-to-noise ratio (S/N) were researched. RESULTS: In MMSE, there was a higher
percent of individuals with alteration for GI group when compared with GII group.
In both SRTS and S/N, the GI group presented lower thresholds when compared with
the GII group for both ears. Regarding the cognitive aspects, no significant
statistical difference between normal and altered groups was observed in the MMSE
for SRTS and S/N for GI and GII in both ears. CONCLUSION: Mild hearing loss
exerted influence on the sentence recognition in silence and in noise. On the
other hand, the cognitive aspects did not interfere in speech recognition in both
silence and noise.
PMID- 27509398
TI - Suppression effect of otoacoustic emissions in term and preterm infants.
AB - PURPOSE: This research aims at verifying the occurrence and magnitude of
suppression effect of otoacoustic emissions evoked by transient stimulus in term
and preterm infants, setting a benchmark for clinical use. METHODS: The study
sample consisted of 40 infants, with a rage of age from five days to four months,
without any risk indicators for hearing loss and otoacoustic emissions present at
birth: the 20 term and 20 preterm infants spent more than five days in the
Neonatal Intensive Care Unit. Linear click was presented at 65 dB Sound Pressure
Level, in blocks of 15 seconds without noise, and with contralateral noise at 60
dB Sound Pressure Level. The reduced response in the presence of noise indicates
positive suppression effect. Mean values of suppression were established and the
comparison between the groups was analyzed statistically. RESULTS: Suppression
occurred in 100% of the children and did not vary as a function of ear side and
between the groups. CONCLUSION: All children presented suppression regardless of
the group. The average suppression obtained on the total population was 0.85 dB.
The minimum recommended criterion for clinical use was a reduction of 0.20 dB in
the overall response.
PMID- 27509399
TI - Fluency aspects of oral narrative task in del22q11.2 syndrome.
AB - PURPOSE: To investigate the fluency aspects of the oral narrative task in
individuals with del22q11.2 syndrome and compare them with those of individuals
with typical language development. METHODS: Fifteen individuals diagnosed with
del22q11.2 syndrome, both genders, aged 7-17 years participated in this study.
They were compared with 15 individuals with typical language development, with
similar gender and chronological age profiles. The oral narrative was elicited
using the book "Frog, Where Are You?", and the fluency aspects were analyzed
according to speech rate and type and frequency of disfluency (typical and
stuttering). The number and duration of pauses were also investigated. The data
were statistically analyzed. RESULTS: The group with del22q11.2 syndrome showed a
higher average when compared with the group without the syndrome for the
percentage of typical disfluencies, mainly hesitation and revision. The group
presenting the syndrome also showed a higher average for stuttering disfluencies,
with pause as the most frequent disfluency. With respect to speech rate, the
group with the syndrome presented a lower average for the number of words and
syllables per minute. Individuals with del22q11.2 syndrome showed greater
difficulties of narration than their peers. CONCLUSION: The fluency aspects of
the oral narrative task in subjects with del22q11.2 syndrome were similar to
those of individuals with typical language development regarding the presence of
hesitation, revision, and pause, but they were different with respect to
frequency of disfluency, which was higher in individuals with the syndrome.
PMID- 27509400
TI - Executive functions and aging.
PMID- 27509401
TI - Is sexual content in new media linked to sexual risk behaviour in young people? A
systematic review and meta-analysis.
AB - BACKGROUND: Social networking and digital media increasingly have an impact on
the lives of young people. We undertook a systematic review and meta-analysis of
studies that examined the relationship between exposure to sexually explicit
websites (SEWs) and 'sexting' (i.e. sending semi-nude or nude photos from a
mobile phone) and the sexual attitudes and practices of young people. METHODS: In
accordance with the Preferred Reporting Items for Systematic Reviews and Meta
Analyses statement, Medline, EMBASE and PsycINFO were searched for papers that
described the statistical association between viewing SEWs or sexting by young
people (defined as 10-24 years) and their sexual attitudes and behaviours.
RESULTS: Fourteen studies, all cross-sectional in design, met the inclusion
criteria. Six studies (10352 participants) examined young people's exposure to
SEWs and eight (10429 participants) examined sexting. There was substantial
variation across studies in exposure and outcome definitions. Meta-analyses found
that SEW exposure was correlated with condomless sexual intercourse (odds ratio
(OR) 1.23, 95% confidence interval (CI): 1.08-1.38, two studies); sexting was
correlated with ever having had sexual intercourse (OR 5.58, 95% CI: 4.46-6.71,
five studies), recent sexual activity (OR 4.79, 95% CI: 3.55-6.04, two studies),
alcohol and other drug use before sexual intercourse (OR 2.65, 95% CI: 1.99-3.32,
two studies) and multiple recent sexual partners (OR 2.79, 95% CI: 1.95-3.63, two
studies). Most studies had limited adjustment for important potential
confounders. CONCLUSIONS: Cross-sectional studies show a strong association
between self-reported exposure to sexual content in new media and sexual
behaviours in young people. Longitudinal studies would provide a greater
opportunity to adjust for confounding, and better insight into the causal
pathways underlying the observed associations.
PMID- 27509402
TI - Human upper airway epithelium produces nitric oxide in response to Staphylococcus
epidermidis.
AB - BACKGROUND: Nitric oxide (NO) is produced by sinonasal epithelial cells as part
of the innate immune response against bacteria. We previously described bitter
taste-receptor-dependent and -independent NO responses to product(s) secreted by
Pseudomonas aeruginosa and Staphylococcus aureus, respectively. We hypothesized
that sinonasal epithelium would be able to detect the gram-positive, coagulase
negative bacteria Staphylococcus epidermidis and mount a similar NO response.
METHODS: Sinonasal air-liquid interface cultures were treated with conditioned
medium (CM) from lab strains and clinical isolates of coagulase-negative
staphylococci and S aureus. NO production was quantified by fluorescence imaging.
Bitter taste receptor signaling inhibitors were utilized to characterize the
pathway responsible for NO production in response to S epidermidis CM. RESULTS: S
epidermidis CM contains a low-molecular-weight, heat, and protease-stabile
product that induces an NO synthase (NOS)-mediated NO production that is less
robust than the response triggered by S aureus CM. The S epidermidis CM
stimulated NO response is not inhibited by antagonists of phospholipase C isoform
beta-2 nor the transient receptor potential melastatin isoform 5 ion channel,
both critical to bitter taste signaling. CONCLUSION: This study identifies an NO
mediated innate defense response in sinonasal epithelium elicited by S
epidermidis product(s). The active bacterial product is likely a small,
nonpeptide molecule that stimulates a pathway independent of bitter taste
receptors. Although the NO response to S epidermidis is less vigorous compared
with S aureus, the product(s) share similar characteristics. Together, the
responses to staphylococci species may help explain the pathophysiology of upper
respiratory infections.
PMID- 27509404
TI - Association between the MTHFR C677T Polymorphism and Breast Cancer Risk: A Meta
Analysis of 23 Case-Control Studies.
PMID- 27509403
TI - Occurrence of the Leech, Pontobdella muricata Linnaeus, on Elasmobranch Species
in the Northern and Central Adriatic Sea.
AB - This study provides a parasitological analysis of the elasmobranch species caught
in the northern and central Adriatic Sea. Sixty-two marine leeches were recorded
on 747 individuals of Raja clavata Linnaeus, 1758 (thornback ray), Myliobatis
aquila Linnaeus, 1758 (common eagle ray), and Torpedo marmorata Risso, 1810
(marbled torpedo ray) caught in 56 hauls over a 5 yr period. All leeches were
identified as Pontobdella muricata, which is a typical ectoparasite of benthic
elasmobranchs. The prevalence of infection ranged from 7.11% on R. clavata to
12.00% on M. aquila. The intensity of infection, the preferential sites of
attachment to the host, and the periodicity of infection were evaluated.
PMID- 27509405
TI - A letter from a Syrian refugee camp in Lebanon: Dr. Aldo Morrone.
PMID- 27509406
TI - Dopamine as a Novel Electrolyte Additive for High-Voltage Lithium-Ion Batteries.
AB - Dopamine, which can be electrochemically oxidized to polydopamine on cathode
surface, was introduced as an electrolyte additive for high-voltage lithium-ion
batteries (LIBs). The addition of 0.1 wt % dopamine to the electrolyte led to the
formation of a polydopamine-containing layer on the cathode, thereby resulting in
suppression of the oxidative decomposition of the electrolyte during high-voltage
operation (up to 4.5 V) of a LiNi1/3Co1/3Mn1/3O2/artificial graphite cell. The
addition of dopamine to the electrolyte improved the capacity retention of the
cell from 136 to 147 mAh g(-1) after 100 cycles at a rate of 1 C and a cutoff
voltage of 4.5 V, while the cycle performance and rate capability with a cutoff
voltage of 4.3 V were comparable to those of the cell without dopamine. Further
evidence of the positive impact of dopamine on high-voltage LIBs was the lower DC
IRs and AC impedances, as well as the retention of the cathode morphology even
after operation at 4.5 V.
PMID- 27509407
TI - Growth differentiation factor 11 (GDF11) - a promising anti-ageing factor - is
highly concentrated in platelets.
AB - Recent research suggests that growth differentiation factor 11 (GDF11) could
reverse age-related diseases and that its blood concentration decreases with age.
This poses plasma from young donors as a therapeutic GDF11 source to treat age
related diseases. In addition, the tissue source of circulating GDF11 remains
unknown. We analysed GDF11 levels in paired samples of serum, plasma and platelet
lysate (PL) from 23 volunteers. Plasma and PL were collected by plateletpheresis.
Here, we show that GDF11 is highly concentrated in platelets and that the
circulating levels reported in previous studies could be biased as a result of
serum sample manipulation.
PMID- 27509408
TI - One-Step and Templateless Electropolymerization Process Using Thienothiophene
Derivatives To Develop Arrays of Nanotubes and Tree-like Structures with High
Water Adhesion.
AB - Here, we report for the first time the possibility to obtain not only arrays of
nanotubes but also tree-like structures with high water adhesion using a one-step
and templateless electropolymerization process. Using thienothiophene
derivatives, particularly thieno[2,3-b]thiophene (Thienothiophene-1) and
thieno[3,2-b]thiophene (Thienothiophene-2), we demonstrate this surface
fabrication in organic solvent (dichloromethane) and without any surfactants. The
formation of nanotubes is due to the stabilization by the polymer of gas bubbles
produced in situ during electropolymerization process, and we show that the water
content plays an important role in the formation of gas bubbles even if it is not
the unique parameter. Using cyclic voltammetry as an electropolymerization
method, the amount of released gas is more significant, but at constant potential
it is much easier to control the nanotube formation. It is also possible to
obtain arrays of tree-like structures when electropolymerizing with high
deposition charges, and the resulting surfaces have high thetaw with extremely
high water adhesion even if the polymers are intrinsically hydrophilic (theta(Y)w
~ 70 degrees ). This work is extremely important for potential applications in
water transportation and harvesting, oil/water separation membranes, energy
systems, and biosensing.
PMID- 27509409
TI - Interessante Frage: Welche anderen Tumoren werden in der Melanom-Nachsorge
mittels PET-CT entdeckt?
PMID- 27509410
TI - Primar kutane CD30(+) lymphoproliferative Erkrankungen.
AB - Primar kutane CD30(+) lymphoproliferative Erkrankungen zahlen zu der zweit
haufigsten Gruppe der kutanen T-Zell-Lymphome (CTCL) und umfassen die
Krankheitsbilder der lymphomatoiden Papulose (LyP) und des primar kutanen
anaplastischen grobetazelligen Lymphoms (cALCL). Beide Erkrankungen haben
klinische, histopathologische und molekulare Gemeinsamkeiten und reprasentieren
ein Spektrum von kutanen CD30(+) lymphoproliferativen Erkrankungen. Man kann LyP
vom cALCL anhand des Zusammenspiels von klinischen und histopathologischen
Befunden unterscheiden. In manchen Patienten konnen LyP und MF gemeinsam
auftreten, oder konnen wahrend des Krankheitsverlaufes entstehen. Mycosis
fungoides (MF), ist die haufigste Form von CTCL und zahlt nicht zur Gruppe der
primar kutanen CD30(+) lymphoproliferativen Erkrankungen. Manche LyP-Patienten
konnen jedoch von beiden Krankheitsbildern gemeinsam betroffen sein. Es ist aber
auch moglich, dass ein MF-Patient LyP-artige Lasionen entwickelt, die eher eine
Manifestation der MF darstellen als zwei unterschiedliche Erkrankungen. Besondere
Vorsicht ist jedoch im Zusammenhang mit CD30(+) transformierten MF-Lasionen
geboten, da die Gefahr besteht, dass diese falschlicherweise als LyP oder cALCL
diagnostiziert werden, was moglicherweise zu einer inadaquaten Behandlung fuhrt.
PMID- 27509411
TI - Primary cutaneous CD30(+) lymphoproliferative disorders.
AB - Primary cutaneous CD30(+) lymphoproliferative disorders are the second most
common group of cutaneous T-cell lymphomas (CTCL) and include lymphomatoid
papulosis (LyP) and primary cutaneous anaplastic large T-cell lymphoma (cALCL).
Both disease entities share overlapping clinical, histopathological, and
molecular features, thus representing a spectrum of cutaneous CD30(+)
lymphoproliferative disorders. LyP may be distinguished from cALCL by
clinicopathological correlation. In some patients, both diseases may coexist at
initial diagnosis or develop over the course of the disease. Mycosis fungoides
(MF), the most common CTCL, is not considered a primary cutaneous CD30(+)
lymphoproliferative disorder, but may occur in some LyP patients. In addition,
LyP-like lesions may develop in MF patients. However, this is frequently a
manifestation of MF rather than a representation of two different disease
entities. Caution also has to be taken in the setting of transformed MF with
lesions expressing CD30, as they may be mistaken for either LyP or cALCL,
resulting in an inadequate therapeutic approach.
PMID- 27509412
TI - On the significance of negative-pressure wound therapy with instillation in
dermatology.
AB - Methods used in the treatment of acute and chronic wounds undergo constant
evolution, reevaluation, and innovation. While negative-pressure wound therapy
(NPWT) is an established treatment modality, the combination of NPWT and
instillation of normal saline as well as solutions with active antiseptic
components for topical treatment of the wound bed represents a novel approach.
The well-known effects of NPWT may thus be combined with those of local
antisepsis. They include a decrease in wound area, induction of granulation
tissue, and reduction in bacterial colonization. To date, studies have focused on
NPWT with instillation for orthopedic/surgical indications, whereas clinical data
in dermatosurgery is limited to case reports or small case series. There are as
yet no randomized prospective studies investigating NPWT with instillation in the
treatment of skin disorders. The goal of this review is to present the method of
NPWT with instillation, to highlight its mode of action as well as possible
complications and contraindications, and to review the recent literature. In
summary, there is increasing evidence that both simple and complicated wounds may
be effectively treated with NPWT with instillation, resulting in markedly
accelerated tissue granulation and thus earlier defect closure.
PMID- 27509413
TI - Zum Stellenwert der Unterdruck-Instillationstherapie in der Dermatologie.
AB - Die Methoden zur Behandlung akuter und chronischer Wunden unterliegen einer
steten Weiterentwicklung, Reevaluierung und Anwendung innovativer Therapieformen.
Die Vakuumtherapie zur Wundbehandlung gehort zu den etablierten
Behandlungsmodalitaten. Ein innovatives Verfahren kombiniert die Vakuumtherapie
mit der automatisierten, kontrollierten Zufuhr und Drainage wirkstoffhaltiger
Losungen zur topischen Wundbehandlung im Wundbett und auch wirkstofffrei durch
Instillation physiologischer Kochsalzlosung (Unterdruck-Instillationstherapie).
Hierdurch konnen die Effekte der konventionellen Vakuumtherapie mit denen der
lokalen Antisepsis kombiniert werden. Hierdurch kommt es zu einer Reduktion der
Wundflache, einer Induktion von Granulationsgewebe sowie einer Reduktion der
Keimbesiedelung der Wunden. Bisher publizierte Studien konzentrieren sich auf die
Anwendung dieses Therapieverfahrens zur Behandlung orthopadisch-chirurgischer
Krankheiten. Die Datenlage bezuglich der Vakuum-Instillationstherapie in der
Dermatochirurgie beschrankt sich derzeit auf Fallberichte und
Einzelfallerfahrungen. Randomisierte, prospektive Studien zum Vergleich der
Vakuum-Instillationstherapie zur Behandlung dermatologischer Krankheitsbilder
existieren bislang nicht. Ziele des vorliegenden Artikels sind die Vorstellung
der Vakuumtherapie mit Instillation einschliebetalich ihres Wirkprinzips, deren
mogliche Komplikationen, die Diskussion erdenklicher Kontraindikationen sowie
eine Ubersicht uber die aktuell verfugbare Datenlage. Zusammenfassend scheint
sich die Evidenz zu verdichten, dass mittels Unterdruck-Instillationstherapie
sowohl einfache als auch komplizierte Wunden effizient behandelt werden konnen,
was sich in einer deutlichen Beschleunigung der Wundgranulation mit konsekutiv
fruher moglichem Defektverschluss aubetaert.
PMID- 27509414
TI - Morphologische Kriterien vesikulobulloser Hauterkrankungen in der konfokalen In
vivo-Laserscanmikroskopie.
AB - HINTERGRUND UND ZIELVORGABEN: Konfokale Laserscanmikroskopie (Reflectance
confocal microscopy; RCM) kann eine nutzliche Methode fur die genaue, schnelle
und nicht-invasive Diagnose fur vesikullobullose Hauterkrankungen (VSD) am
Krankenbett sein. Das primare Ergebnis dieser Studie war eine deskriptive
statistische Analyse von RCM-Merkmalen, die mit einer ausgewahlten Gruppe an VSD
einhergehen. PATIENTEN UND METHODEN: Monozentrische Beobachtungsstudie an einer
Universitatsklinik fur Dermatologie. Vierzig Hautlasionen bei 24 Patienten mit
bullosem Pemphigoid (BP), Infektion mit Varizella Zoster (VZI) oder allergischer
Kontaktdermatitis (ACD) wurden ausgewertet. ERGEBNISSE: Patienten mit BP, VZI und
ACD wurden auf die Anwesenheit eines grobetaen Spektrums an RCM-Merkmalen hin
untersucht, darunter die histopathologische Korrelation von Spongiose,
Vesikel/Hautblasen, epidermaler Nekrose, pleomorphen, ballonierte Keratinozyten
und entzundlichen Infiltraten. Die drei Erkrankungen zeigten spezifische Muster
fur Auftreten dieser RCM-Merkmale. Wir identifizierten mit Hilfe einer
multivariaten Regressionsanalyse einen Satz morphologischer Merkmale bei BP
(Vesikel/Hautblasen an der dermoepidermalen Junktionszone, entzundliche
Infiltrate in Hautblasen und basalen Epidermisschichten, Spongiose in basalen
Epidermisschichten), VZI (Akantholyse im Stratum spinosum, epidermale Nekrose,
pleomorphe, ballonierte Keratinozyten, multinukleare Riesenzellen) und ACD
(Mikrovesikel, Spongiose und auffallige entzundliche Infiltrate im Stratum
granulosum/spinosum). SCHLUSSFOLGERUNGEN: RCM scheint ein nutzliches Werkzeug bei
der Analyse und der Unterscheidung einer ausgewahlten Gruppe von VSDs zu sein und
bietet eine gute Korrelation mit histopathologischen Untersuchungsergebnissen.
PMID- 27509415
TI - Morphologic criteria of vesiculobullous skin disorders by in vivo reflectance
confocal microscopy.
AB - BACKGROUND AND OBJECTIVES: Reflectance confocal microscopy (RCM) may be a useful
method for accurate, rapid, and noninvasive bedside diagnosis of vesiculobullous
skin diseases (VSD). The main outcome measure of this study was a descriptive
statistical analysis of RCM features associated with selected group of VSD.
PATIENTS AND METHODS: Single-center, observational study at a university-based
dermatology department. Forty skin lesions in 24 patients with bullous pemphigoid
(BP), varicella zoster virus infection (VZI), or allergic contact dermatitis
(ACD) were assessed. RESULTS: Patients with BP, VZI, and ACD were assessed for
the presence of a large spectrum of RCM features, among others including
histopathological correlates for spongiosis, vesicles/blisters, epidermal
necrosis, pleomorphic ballooned keratinocytes, and inflammatory infiltrate. The
three conditions showed distinct patterns of occurrence with respect to these RCM
features. Using a multivariate regression model, we identified sets of
morphologic features in BP (vesicles/blisters at the dermoepidermal junction,
inflammatory infiltrate within blisters and basal epidermal layers, spongiosis in
basal epidermal layers), VZI (acantholysis in the stratum spinosum, epidermal
necrosis, pleomorphic ballooned keratinocytes, multinucleated giant cells), and
ACD (microvesicles, spongiosis, and prominent inflammatory infiltrate in the
stratum granulosum/spinosum). CONCLUSIONS: RCM seems to be a useful tool in the
evaluation and differentiation of a selected group of VSD, and offers a good
correlation with histopathological findings.
PMID- 27509416
TI - Retrospective chart analysis of incidental findings detected by (18) F
fluorodeoxyglucose-PET/CT in patients with cutaneous malignant melanoma.
AB - BACKGROUND AND OBJECTIVES: (18) F-fluorodeoxyglucose positron emission
tomography/computed tomography (FDG-PET/CT) frequently reveals incidental
findings. The present study focused on incidental FDG-PET/CT findings in
cutaneous melanoma patients, and verified their relevance with respect to further
diagnostic measures and interventions. PATIENTS AND METHODS: Medical records of
181 consecutive melanoma patients were retrospectively evaluated to verify the
management of incidental findings, with particular emphasis on histological
findings. RESULTS: Thirty-three of 181 (18 %) patients showed 39 relevant
incidental findings, located in the colorectal tract (n = 15 patients), thyroid
(n = 8), prostate (n = 2), locomotor system (n = 2), lymph nodes (n = 2),
parotid gland (n = 1), tonsils (n = 1), kidneys (n = 1), and gallbladder (n
= 1). Performed in 25 patients, additional diagnostic procedures revealed a
clinical correlate in 21 cases. Sixteen of 21 patients had tumoral involvement,
including five malignant lesions (four colorectal and one prostate carcinoma).
The malignancies were diagnosed at an early stage, and successfully removed in
the majority of cases. CONCLUSIONS: The diagnostic use of FDG-PET/CT is routinely
recommended for stage IIC melanoma and higher, and is widely accepted as
indication. This study effectively identified otherwise undetected cancers,
especially colorectal malignancies. Early interventions were possible in most
cases. Incidental findings on FDG-PET/CT should be worked up with appropriate
diagnostic measures, considering the patient's condition and wishes.
PMID- 27509417
TI - Retrospektive Analyse von Zufallsbefunden, die bei Patienten mit kutanem malignen
Malignom durch (18) F-Fluordeoxyglucose-PET/CT erhoben wurden.
AB - HINTERGRUND UND ZIELE: Bei der (18) F-Fluordeoxyglucose
Positronenemissionstomographie/Computertomographie (FDG-PET/CT) ergeben sich
haufig Zufallsbefunde. In der vorliegenden Studie konzentrierten wir uns auf
mittels FDG-PET/CT erhaltene Zufallsbefunde bei Patienten mit kutanem Melanom und
uberpruften deren Relevanz hinsichtlich weiterer diagnostischer Mabetanahmen und
Interventionen. PATIENTEN UND METHODEN: Die Krankenakten von 181 konsekutiven
Melanom-Patienten wurden retrospektiv ausgewertet, um das Management von
Zufallsbefunden zu dokumentieren. Der Schwerpunkt lag dabei auf den
histologischen Befunden. ERGEBNISSE: Bei 33 von 181 (18 %) Patienten lagen 39
relevante Zufallsbefunde vor, und zwar im Kolorektalbereich (n = 15 Patienten),
in der Schilddruse (n = 8), der Prostata (n = 2), dem Bewegungsapparat (n = 2),
in Lymphknoten (n = 2), der Parotis (n = 1), den Mandeln (n = 1), den Nieren (n =
1) und der Gallenblase (n = 1). Bei 25 Patienten schlossen sich weitere
diagnostische Verfahren an, wobei in 21 Fallen ein klinisches Korrelat
nachgewiesen wurde. Bei 16 von 21 Patienten ergab sich eine Neoplasie, darunter
funf maligne Lasionen (vier Kolonkarzinome und ein Prostatakarzinom). Die
Malignome wurden fruhzeitig diagnostiziert und in der Mehrzahl der Falle
erfolgreich entfernt. SCHLUSSFOLGERUNGEN: Der Einsatz der FDG-PET/CT als Routine
Diagnostik wird in den Leitlinien empfohlen und ist indiziert bei malignem
Melanom ab Stadium IIC. In dieser Studie wurden auf effektive Weise ansonsten
nicht erkannte Krebserkrankungen, insbesondere Kolonkarzinome, detektiert. In den
meisten Fallen war eine fruhe Intervention moglich. Zufallsbefunde durch FDG
PET/CT sollten, unter Berucksichtigung des Zustands und der Wunsche des
Patienten, mit den geeigneten diagnostischen Mabetanahmen abgeklart werden.
PMID- 27509418
TI - Tinea capitis: Erregerspektrum und Epidemiologie im zeitlichen Wandel.
AB - HINTERGRUND: Die Tinea capitis ist die haufigste Dermatomykose des Kindesalters.
Das Erregerprofil zeigt unterschiedliche geographische Verteilungsmuster und
variiert im Laufe der Zeit. PATIENTEN UND METHODIK: Zwischen 1990-2014 an der
Wurzburger Universitatsklinik fur Dermatologie erhobene Daten von 150 Patienten
mit mykologisch gesicherter Tinea capitis wurden hinsichtlich Alter, Geschlecht
und Erregerspektrum analysiert und uber zwei Zeitraume von jeweils 12,5 Jahren
miteinander verglichen. ERGEBNISSE: Obwohl eine Tinea capitis am haufigsten bei
Kindern der Altersgruppe zwischen 0 und 5 Jahren diagnostiziert wurde, lag der
Anteil betroffener Erwachsener mit 16 % hoher als bislang berichtet. Der zoophile
Dermatophyt Microsporum canis konnte am haufigsten als Erreger der Tinea capitis
identifiziert werden, jedoch war ein Anstieg von Infektionen mit den
anthropophilen Pilzen Trichophyton tonsurans und Trichophyton rubrum zu
verzeichnen. Tendenziell sank der Anteil zoophiler im Verhaltnis zu den
anthropophilen Erregern. Im zeitlichen Verlauf zeigte sich eine zunehmende
Heterogenitat des Erregerspektrums: Dermatophyten wie Trichophyton soudanense und
Trichophyton violaceum, Trichophyton anamorph von Arthroderma benhamiae sowie
Trichophyton schoenleinii und Microsporum audouinii konnten erstmalig bzw. nach
langer Zeit wieder erneut isoliert werden. SCHLUSSFOLGERUNGEN: Wenngleich
Microsporum-canis-Infektionen noch dominieren, sind zunehmend anthropophile
Erreger nachzuweisen. Angesichts des unerwartet hohen Anteils von Erwachsenen
sollte eine Tinea capitis in allen Altersgruppen differenzialdiagnostisch in
Betracht gezogen werden.
PMID- 27509419
TI - Tinea capitis: temporal shift in pathogens and epidemiology.
AB - BACKGROUND: Tinea capitis is the most common type of dermatomycosis in children.
Its pathogen profile shows geographic variations as well as temporal shifts.
PATIENTS AND METHODS: Data from 150 patients with mycologically confirmed tinea
capitis treated at the Department of Dermatology, University Hospital Wurzburg,
between 1990 and 2014 were analyzed with respect to gender, age, and pathogen
spectrum. Two time periods, each 12.5 years long, were compared. RESULTS:
Although tinea capitis was most frequently diagnosed in children between the ages
of 0 and 5, the percentage of adults (16 %) was higher than previously reported.
The zoophilic dermatophyte Microsporum canis was most frequently identified as
the causative agent of tinea capitis. However, there was a rise in infections
caused by the anthropophilic fungi Trichophyton tonsurans and Trichophyton
rubrum, and also a trend towards a lower percentage of zoophilic versus
anthropophilic pathogens. Over the course of time, we observed an increase in the
diversity of the pathogen spectrum. Dermatophytes such as Trichophyton
soudanense, the Trichophyton anamorph of Arthroderma benhamiae, Trichophyton
schoenleinii, and Microsporum audouinii were isolated either for the first time
or for the first time after a long hiatus. CONCLUSIONS: Although Microsporum
canis infections still predominate, there has been an increase in anthropophilic
pathogens. Given the unexpectedly high percentage of adults, tinea capitis should
be included in the differential diagnostic considerations in all age groups.
PMID- 27509420
TI - Generalized morphea with development of bullous lesions at the site of surgical
scars.
PMID- 27509421
TI - Generalisierte zirkumskripte Sklerodermie (Morphea) mit bullosen Lasionen an
Operationsnarben.
PMID- 27509422
TI - Infektionsassoziiertes gemeinsames Auftreten von Psoriasis pustulosa, Pemphigus
foliaceus und leukozyoklastischer Vaskulitis.
PMID- 27509423
TI - Coincidence of annular pustular psoriasis, pemphigus foliaceus, and
leukocytoclastic vasculitis associated with chronic cholecystitis.
PMID- 27509424
TI - Vulvar and areolar melanosis: a case report and review of the literature.
PMID- 27509425
TI - Melanose der Vulva und Areola: Fallbericht und Literaturubersicht.
PMID- 27509426
TI - Effektive Behandlung einer durch Leishmania tropica verursachten kutanen
Leishmaniose mit topischer, photodynamischer Therapie.
PMID- 27509427
TI - Effective treatment of cutaneous leishmaniasis caused by Leishmania tropica with
topical photodynamic therapy.
PMID- 27509428
TI - Dramatischer Verlauf einer malignen atrophen Papulose (Morbus Kohlmeier-Degos)
mit todlichem Ausgang.
PMID- 27509429
TI - Generalisierte Herpes-simplex-Virus-Infektion bei Morbus Darier.
PMID- 27509430
TI - Generalized herpes simplex virus infection in Darier's disease.
PMID- 27509431
TI - Keratotische Papeln und Plaques genitogluteal.
PMID- 27509432
TI - Keratotic papules and plaques in the genitogluteal region.
PMID- 27509433
TI - Perkutane Ultraschall-gesteuerte Durchstichdrainage therapierefraktarer Serome
nach Lymphknotenexzision.
PMID- 27509434
TI - Percutaneous ultrasound-guided drainage of needle aspiration-refractory seromas
following lymph node excision.
PMID- 27509435
TI - S1-Guidelines on UV phototherapy and photochemotherapy.
AB - Known in part since antiquity, the salutary effects of sunlight again garnered
increasing attention in the second half of the 19(th) century. The development of
a device for ultraviolet irradiation of cutaneous tuberculosis by Finnsen at the
onset of the twentieth century truly marked the beginning of modern phototherapy.
In dermatology, treatment methods almost exclusively use wavelengths below the
visible light range (ultraviolet light). Since the early 1970s, increasingly
powerful artificial light sources have become available for UVB and UVA therapy
as well as the combination of UVA and photosensitizers (photochemotherapy). High
structural and procedural quality standards are an essential prerequisite for the
implementation of effective as well as safe phototherapy. The following
guidelines outline the current consensus of leading experts in the field of
phototherapy with respect to indications, contraindications, and side effects of
various treatment options available. Particular focus is also on adequate UV
doses at the beginning and over the further course of treatment as well as on
management of side effects.
PMID- 27509438
TI - Forschungspreis der Jorg Wolff-Stiftung - Arnold Rikli-Preis 2016.
PMID- 27509437
TI - Osterreichische Gesellschaft fur Dermatologie und Venerologie (OGDV).
PMID- 27509440
TI - Kongresskalender 2016.
PMID- 27509439
TI - S1-Leitlinie zur UV-Phototherapie und Photochemotherapie.
AB - Die heilsame Wirkung des Sonnenlichts war teilweise schon im Altertum bekannt und
fand in der zweiten Halfte des 19. Jahrhunderts wieder zunehmend Beachtung. Den
Beginn der modernen Phototherapien markiert die Entwicklung einer Apparatur zur
ultravioletten Bestrahlung der Hauttuberkulose durch Finnsen zu Beginn des
zwanzigsten Jahrhunderts. Zur Therapie von Hauterkrankungen finden beinahe
ausschliebetalich die spektralen Bereiche unterhalb des sichtbaren Lichtes
(ultraviolett) Anwendung. Seit den 1970er Jahren stehen zunehmend leistungsfahige
kunstliche Strahlenquellen bereit fur die Therapie mit UVB, UVA und die
Kombination von UVA mit Photosensibilisatoren (Photochemotherapie). Hohe
strukturelle und prozedurale Qualitatsstandards sind unabdingbare Voraussetzung
fur die Durchfuhrung einer gleichermabetaen wirkungsvollen wie auch sicheren
Phototherapie. Die Leitlinie formuliert den aktuellen Konsens fuhrender Experten
auf dem Gebiet der Phototherapie in Bezug auf die Indikationen fur die jeweiligen
Therapieverfahren, deren Gegenanzeigen und Nebenwirkungen und insbesondere fur
die Wahl der korrekten Dosis zu Beginn und im Verlauf einer Therapie sowie das
Management von Nebenwirkungen.
PMID- 27509441
TI - Cancer incidence in Holocaust male survivors-An Israeli cohort study.
AB - Previous studies, often using proxy exposure assessment and not controlling for
individual risk factors, suggested higher cancer risk in Holocaust survivors. We
have used individual-level data from a male cohort of Israeli civil servants
recruited in 1963 to investigate cancer incidence in Holocaust survivors,
controlling for potential confounders. The analysis included 4,669 Europe-born
subjects; 689 exposed = E (immigrated to Israel after 1939 and reported of being
in Nazi camps during World War II); 2,307 potentially exposed = PE (immigrated to
Israel after 1939 and reported of not being in Nazi camps); and 1,673 non-exposed
= NE (immigrated to Israel prior to 1939). Vital status and cancer incidence in
the cohort were determined based on national registries. Socioeconomic level,
health behaviors and cancer incidence were compared between the groups and Cox
proportional hazards regression models adjusting for potential confounders
assessed hazard risk ratios for cancer by exposure status. All-cause mortality
was studied as a competing risk. In total, 241, 682, and 522 cancer cases were
diagnosed in the E, PE, and NE, respectively. Compared with the NE, all-site
cancer incidence was higher in the E (HR = 1.13, 95%CI 0.97-1.32) but not in the
PE. All-cause mortality competed with all-site invasive cancer incidence in the E
group (HR = 1.18, 95%CI 1.02-1.38). Colorectal and lung cancer seemed to be
positively though non-significantly associated with the exposure while prostate
cancer was not. Male Holocaust survivors may be at a weakly increased risk for
all-site, colorectal and lung cancer. The role of age at exposure and residual
confounding should be further investigated.
PMID- 27509443
TI - The Reactive-Diffusive Length of OH and Ozone in Model Organic Aerosols.
AB - A key step in the heterogeneous oxidation of atmospheric aerosols is the reaction
of ozone (O3) and hydroxyl radicals (OH) at the gas-particle interface. The
formation of reaction products and free radical intermediates and their spatial
distribution inside the particle is a sensitive function of the length over which
these oxidants diffuse prior to reaction. The reactive-diffusive length of OH and
ozone at organic aerosol interfaces is determined by observing the change in the
effective uptake coefficient for size-selected model aerosols comprising a
reactive core and a thin nanometer-sized (0-12 nm) organic shell. The core and
shell materials are selected so that they are immiscible and adopt an assumed
core-shell configuration. The results indicate a reactive-diffusive length of 1.4
nm for hydroxyl (OH) radicals in squalane and 1.0 nm for ozone in squalene.
Measurements for a purely diffusive system allow for an estimate for diffusion
constant (1.6 * 10(-6) cm(2)/s) of ozone in squalane to be determined. The
reactive-diffusive length offers a simple first order estimate of how shielding
of aerosols by immiscible layers can alter estimates of oxidative lifetimes of
aerosols in the atmosphere.
PMID- 27509444
TI - iHEART: a miniaturized near-infrared in-line gas sensor using heart-shaped
substrate-integrated hollow waveguides.
AB - A novel heart-shaped substrate-integrated hollow waveguide (hiHWG) was integrated
with a near-infrared micro-spectrometer (MUNIR) for sensing natural gases,
resulting in an ultra-compact near-infrared gas sensing system - iHEART. The
iHEART system was evaluated using two different MUNIR spectrometers, and the
performance was compared with a laboratory NIR spectrometer for gas analysis
based on an acousto-optic tunable filter (AOTF). The spectral data were pre
processed using the 1(st) derivative Savitzky-Golay algorithm, and then used for
establishing multivariate regression models based on partial least squares (PLS).
The root mean square errors of prediction (RMSEPs) obtained for major components
of natural gas with both iHEART systems were similar to those associated with the
AOTF spectrophotometer combined with a conventional long-path measurement cell.
It was demonstrated that the iHEART system has significant potential for the
development of compact in-line gas sensing systems, thus facilitating monitoring
of (petro)chemically relevant processes and products. However, the flexibility
and modularity of the system also allows tailoring iHEART to a wide range of
other relevant analytical measurement scenarios requiring short response times
and minute gas sample volumes.
PMID- 27509445
TI - Does Increased Duodenal Intraepithelial Lymphocytosis Always Equate With Marsh 1
Lesion?
PMID- 27509446
TI - Multipolar versus monopolar radiofrequency ablation for hepatocellular carcinoma
in the caudate lobe: Results of a propensity score analysis.
AB - AIM: This study aimed to compare multipolar radiofrequency ablation (RFA) with
monopolar RFA as the major treatment for nodules of hepatocellular carcinoma in
the caudate lobe. METHODS: This retrospective study was approved by the
institutional review board. Data were reviewed from 101 patients who met the
Milan criteria and were treated by multipolar RFA (n = 22) or monopolar RFA (n =
79). After propensity score matching, complications and local tumor progression
were compared between the two groups. RESULTS: Before propensity score matching
(n = 101), the 2-year relapse-free survival rates for multipolar and monopolar
RFA (65.1% vs. 38.8%, respectively; P = 0.064) and the local tumor progression
rate (12.5% vs. 14.9%, respectively; P = 0.313) were not significantly different.
There were no significant differences between the two RFA techniques by treatment
efficacy of transcatheter hepatic arterial embolization, location of tumor, and
puncture route. After matching (n = 44), the 2-year relapse-free survival rate
for the multipolar and monopolar groups (65.1% vs. 22.7%, respectively; P =
0.004) was significantly different, and the local tumor progression rate (12.5%
vs. 22.9%, respectively; P = 0.004) was significantly different. No severe
complications occurred in the patients treated by multipolar RFA. CONCLUSION:
Multipolar RFA appears to be a safe and effective method for hepatocellular
carcinoma nodules in the caudate lobe.
PMID- 27509447
TI - The impact of characteristics of nurses' relationships with their supervisor,
engagement and trust, on performance behaviours and intent to quit.
AB - AIMS: The aim of this study was to investigate the influence of characteristics
of nurses' relationship quality with their manager on engagement and trust, onto
in-role or discretionary behaviours and intent to quit. BACKGROUND: Nurses having
a good relationship with their manager are seen as important, yet the mechanisms
of how such relationships are beneficial, or which aspects of the relationship
are important, is less clear. Two possible mechanisms are through the nurse being
more engaged in work, or through building their trust in their employer. In turn,
engagement and trust may impact in-role and discretionary behaviours as well as
staff retention. DESIGN: Cross-sectional. METHOD: An online survey in 2013 of 459
nurses across Australia. RESULTS: Structural analyses indicated that the affect
dimension of relationship quality was negatively related to engagement, whereas
contribution and respect were positively related to engagement. The affect and
respect aspects were positively related to trust. Engagement positively related
to discretionary and in-role behaviours. Engagement and trust were negatively
related to quit intention, as was the loyalty dimension of the nurses'
relationship with their supervisor. However, perceptions of variability in their
team's relationship quality with their leader was negatively related to trust and
positively related to intent to quit. CONCLUSIONS: Nurse managers with a nuanced
understanding of social exchange at work are likely to maintain more engaged,
well-performing and stable nursing teams. In particular, a willingness by the
supervisor to come to their nurses' defence and having a consistent standard of
relationship quality across their nurses is likely to improve nurse retention.
PMID- 27509449
TI - Decarboxylative Annulation of alpha-Amino Acids with gamma-Nitroaldehydes.
AB - Indolizidine and quinolizidine derivatives are readily assembled from proline or
pipecolic acid and gamma-nitroaldehydes by means of a decarboxylative annulation
process. These reactions are promoted by simple acetic acid and involve
azomethine ylides as reactive intermediates. The method was applied to the
synthesis of an epiquinamide analog.
PMID- 27509450
TI - Evaluation of 126 Consecutive Stereotactic Procedures: Brain Biopsy, Diagnostic
Yield, Accuracy, Non-Diagnostic Results, Complications and Follow-up.
AB - AIM: A retrospective analysis of 126 consecutive computed tomography (CT)-guided,
frame-based stereotactic procedures in 121 patients is presented to evaluate the
diagnostic yield, accuracy, complications, management of non-diagnostic cases and
followup. MATERIAL AND METHODS: The medical records of the identified patients
were investigated retrospectively. Age, sex, surgical procedures,
histopathological diagnosis, diagnostic yield, accuracy, complications,
management of non-diagnostic cases and follow-up were analyzed in 121 consecutive
patients. Stereotactic procedures were performed by the author by using Leksell's
stereotactic system, and stereotactic biopsies were conducted under local
anesthesia except for those patients who were not able to tolerate this
treatment. These patients had control CT scans two hours after the operation.
RESULTS: Patient age ranged from 2 to 82 years (mean 48 years). Stereotactic
biopsy was performed in 112 patients. Cyst and abscess aspiration, intracystic
catheter replacement and tumor resection with stereotactic craniotomy were among
the other procedures. The diagnostic yield was 93%, and the histological accuracy
was 63% with no mortality. Craniotomy and hematoma evacuation were required in
two cases. The patients were followed up from one month to 17 years. CONCLUSION:
Frame-based stereotactic biopsy is a safe and efficacious method with acceptable
complications. Experience is important, but not sufficient for preventing
complications and performing procedures accurately. Necrosis and gliosis are the
most common non-diagnostic findings. Empirical treatment with presumptive
diagnoses based on clinical and radiological findings and close clinical follow
up may not affect patients adversely. The follow-up of patients through
examination and imaging is important to allow the revision of treatment when
necessary.
PMID- 27509451
TI - The Impact of the Stage and Tumor Size on Rare Brain Metastasis of Cervical
Cancer.
AB - AIM: To investigate the clinical features, prognostic factors and survival times
of cervical cancer patients with brain metastasis. MATERIAL AND METHODS: We
retrospectively reviewed the medical records of 820 patients with cervical
cancer. Data were analyzed using SPSS version 12.0 statistical software (SPSS,
Chicago, IL, USA). Overall survival, time interval from diagnosis of cervical
cancer to identification of brain metastasis, and median survival time after
diagnosis of brain metastasis were calculated using Kaplan-Meier curve analysis.
The log-rank test was used to compare differences in survival. Differences were
assumed statistically significant when p-values were < 0.05. RESULTS: The
incidence of brain metastases from cervical cancer in our institution was 1.82%
(15/820) over a ten-year period. The median time interval from diagnosis of
cervical cancer to detection of brain metastasis was 12.5 months (range: 2.9-91.9
months). Stage and tumor diameter were found to be significant relating to the
interval from diagnosis of cervical cancer to detection of brain metastasis
(p=0.001 for both). CONCLUSION: This study provides much information about the
prognosis of patients with brain metastases from cervical cancer and highlights
the importance of initial stage and tumor diameter when determining the time
interval until development of brain metastasis.
PMID- 27509452
TI - Gamma Knife Radiosurgery for Arteriovenous Malformations: Clinical Series of 199
Patients.
AB - AIM: Cerebral arteriovenous malformations (AVM) are pathological connections
between arteries and veins without capillaries. Stereotactic radiosurgery (RS) is
a proven and accepted treatment method for cerebral AVMs. Our objective was to
analyze the factors influencing the clinical outcome in patients suffering from
AVMs. MATERIAL AND METHODS: We retrospectively reviewed 199 patients who were
treated with Gamma-Knife RS for intracranial AVMs between 13 October 2005 and 31
October 2010. There were 89 male, 110 female patients with a median age of 32
years (range, 3-74 years). Obliteration was assessed with MRI angiography and DSA
imaging. RESULTS: Complete obliteration rate after RS was 71 % (141 out of 199),
including second RS treatments. In terms of obliteration rates, there was no
significant difference between patients younger and older than 21 years old
(p=0.669). After RS, 3 patients died due to intracranial hemorrhage and 1 died of
heart disease. Death from AVM was determined as 1.5 %. Intracranial hemorrhage
was observed in 7 (3.5 %) patients post-RS. CONCLUSION: Obliteration was found to
be associated with Spetzler-Martin Grade, Pollock-Flickinger Grade, AVM volume,
RS dose, bleeding history before RS and no previous embolization before RS. Gamma
knife RS is an effective treatment method for the treatment of AVMs both for
pediatric and adult patients. It provides high obliteration and low mortality
rates.
PMID- 27509453
TI - Effectiveness of GFAP in Determining Neuronal Damage in Rats with Induced Head
Trauma.
AB - AIM: To determine whether the serum level of glial fibrillary acidic protein
(GFAP), an important indicator of neuron damage, correlates with the extent of
tissue damage in the rat with induced head trauma and to obtain data in order to
avoid unnecessary cranial computed tomography analyses. MATERIAL AND METHODS:
Three-month-old male Sprague-Dawley rats were used. Rats were divided into 5
groups. The experimental head trauma model was examined in five groups (n=8) as
follows: The control group had no intervention; Group 1: Head trauma was induced
by dropping a 25 mg ball from a height of 20 cm; Group 2: Head trauma was induced
by dropping a 50 mg ball from a height of 20 cm; Group 3: Head trauma was induced
by dropping a 50 mg ball from a height of 80 cm; Group 4: Head trauma was induced
by dropping a 100 mg ball from a height of 80 cm. Thus, according to the Newton's
Law, respectively 0.05, 0.1, 0.2 and 0.4 N trauma was created. Serum GFAP levels
were analyzed and the damage to cerebral tissues was evaluated in all groups.
RESULTS: We determined that number of apoptotic cells and particularly the number
of GFAP (+) protoplasmic astrocytes at the perilesional region of the cortex
increased in association with the increased serum GFAP level as long as the
severity of the trauma increased. CONCLUSION: Serum GFAP concentration can be
used as a marker of the severity of head trauma and traumatic brain injury.
However, more animal studies are required to reflect this result in clinical
practice.
PMID- 27509454
TI - Contribution of Neural Elements to Thoracic Stability.
AB - AIM: Studies of spinal biomechanics typically do not focus on the contributions
to range of motion (ROM) of the primary components of the spinal canal, dura,
arachnoid, pia, spinal cord, nerve roots, ligaments, and vessels. We sought to
determine the stability offered by these soft tissues in vitro. MATERIAL AND
METHODS: Human cadaveric segments were tested intact, after osteoligamentous
destabilization, and after transection of T8-9 spinal canal components. Specimens
were induced into flexion, extension, axial rotation, and lateral bending using
non-constraining, non-destructive pure moment while tracking motion response
stereophotogrammetrically. The range of motion (ROM) was compared in each
condition after adjusting for soft tissue creep. RESULTS: After spinal canal
element transection, ROM increased in all directions (mean 4.7%). This increase
was most pronounced during lateral bending (p=0.055). The cumulative ROM from all
directions of loading showed a statistically significant mean increase of 3.3%
(p=0.040). CONCLUSION: Sectioning of canal elements was found to cause a
measurable increase in ROM. Although nonviable tissues were tested, living
tissues are also likely to contribute to spinal stability.
PMID- 27509455
TI - Optic Nerve Hemangioblastomas?A Review of Visual Outcomes.
AB - Supratentorial hemangioblastomas (HBLs) are exceedingly uncommon. They account
for less than 5% of all central nervous system HBLs. The commonest location is
the cerebral cortex. Rarely, they can involve the visual pathway. Most of the
reports have focused on the differential diagnosis, since depending on the
location they can often resemble optic nerve gliomas or meningiomas of the optic
nerve sheath. In this study, we describe a 67-year-old man with progressive
diminution of vision in the left eye with an optic nerve hemangioblastoma. There
was no history of von Hippel-Lindau disease. We discuss the diagnostic
challenges, and review the visual presentation and visual outcomes in these
patients. This report, we believe, may add further clarity in counseling patients
with an optic nerve lesion and the factors in surgical decision-making.
PMID- 27509456
TI - Does Right-Sided Language Lateralization on BOLD-fMRI Affect Postoperative
Language Outcome for AVM Patients?
AB - AIM: For cerebral arteriovenous malformations (AVMs) involving language areas,
right-sided language lateralization on functional magnetic resonance imaging
(fMRI) has been reported, which is regarded as language cortex reorganization.
The authors attempted to study if this right-sided language lateralization
affects postoperative language outcome. MATERIAL AND METHODS: Clinical and
imaging data of 43 right-handed AVM patients who underwent preoperative fMRI were
retrospectively reviewed. All lesions involved the language cortex, with the
Broca area involved in 13 patients and the Wernicke area involved in 30 patients.
Lateralization indices (LI) of BOLD signal activations were calculated to
determine language lateralization. All patients underwent craniotomy and total
resection. Western aphasia battery (WAB) was used to evaluate language functions
preoperatively, 1-2 weeks after surgery and 6-30 months after surgery. RESULTS:
On preoperative fMRI, right-sided lateralization was observed in 18 patients
(41.9%, R Group), including 3 with rightsided lateralization in the Broca area
alone, 14 in the Wernicke area alone, and 1 in both areas. The other 25 patients
were non-rightsided lateralized (NR Group). One week after surgery, 7 patients in
the R Group (38.9%) and 11 patients in the NR Group (44.0%) had language function
deterioration, and no significant difference was found (p=0.983). At long-term
follow-up, 3 patients in the R Group (16.7%) and 4 patients in the NR Group
(16.0%) still had aphasia, and no significant difference was observed (p=1.000).
CONCLUSION: Although right-sided lateralization on fMRI might suggest language
cortex reorganization, it is not a factor predicting better postoperative
language outcome for AVM patients.
PMID- 27509457
TI - Neuroprotective Effects of Chronic Fenofibrate Treatment via Modulating the
Immunoreactivity of Cleaved Caspase-3 in Stroke Induced by Transient Middle
Cerebral Artery Occlusion Rat Model.
AB - AIM: Current stroke therapies include lipid-lowering drugs, which reduce
inflammation and serve to stabilize the atherosclerotic plaque to demonstrate
better outcome and neuroprotection. Peroxisome proliferator activated receptors
(PPAR) ? regulates lipid homeostasis and is a target of fibrates, which have a
neuroprotective function by various mechanisms. In this study, we aimed to
evaluate the role of the PPAR? agonist, fenofibrate, in the modulation of cleaved
caspase-3 immunoreactivity and at the final infarct volume in an experimental
ischemia/reperfusion rat model by induced transient proximal middle cerebral
artery occlusion. MATERIAL AND METHODS: A total of 65 male Sprague Dawley rats
were allocated into 4 groups; sham (n =5), experiment 1 (n=20), experiment 2
(n=20), experiment 3 (n=20). All experiment groups were divided to 3 subgroups in
order to evaluate the final infarct volume at 24th hour (n=5) and the
immunoreactivity of cleaved caspase -3 at different time periods [at first hour
(n=5), at 6th hour (n=5), at 24th hour (n=5)] after transient middle cerebral
artery occlusion (MCAo). At the study, the experiment groups (Experiment 1 and
Experiment 2) were received the fenofibrate-diet during 14 days before ischemia
procedure. All animals were sacrificed at 24th hours after MCAo. Infarction
volumes were calculated from 2,3,5,triphenyltetrozolium chloride (TTC)- stained
brain sections. RESULTS: We found that fenofibrate-therapy reduced significantly
more body weight than the other experiment groups (p < 0.05). At the time
intervals, a decrease of immunoreactivity of cleaved caspase-3 was significantly
observed with fenofibrate therapy after MCAo (p < 0.05). Chronic fenofibrate
treatment before cerebral ischemia significantly reduced the infarction size
after MCAo compared with the other groups (respectively; p = 0.011 and p <
0.000). CONCLUSION: Fenofibrate treatment has neuroprotective effects on middle
cerebral artery infarcts.
PMID- 27509458
TI - A Modified Mini-Pterional (Subfrontal-Suprapterional) Approach to MCA Bifurcation
Aneurysms with Minimal Dissection of the Temporal Muscle.
AB - There are a number of different surgical approaches in middle cerebral artery
(MCA) aneurysm surgery. Evolution from the classical pterional approach towards
smaller modified approaches took place over the years. In the present report, we
describe a new modified approach in the treatment of MCA aneurysms, which is
almost exclusively subfrontal. A modified approach was used on three patients
with MCA bifurcation aneurysms. Craniotomy was subfrontal and suprapterional with
minimal dissection of the temporal muscle and no drilling of the pterion. In all
three cases, after establishing proximal control and dissecting the M1 carefully,
retraction of the frontal lobe elevated the sylvian fissure and allowed opening
of the fissure. The aneurysm could be identified easily and clips were applied.
There was no infection and complete aneurysm clipping was achieved in all 3
patients. The described minimal craniotomy to the MCA through a subfrontal
suprapterional approach allows dissection of peripheral MCA bifurcation aneurysms
without any problems.
PMID- 27509459
TI - Calvarial Reconstruction of Small-Size Skull Defects Performing "8 Cranioplasty"
in Children: Surgical Experience, Clinical Results and Treatment Algorithm.
AB - AIM: To report our clinical experience, surgical treatment algorithm and
technique in the reconstruction of uncomplicated and small-size calvarial defects
by performing autologous split-bone grafting technique on anatomical findings and
patients" outcome. MATERIAL AND METHODS: We covered the defective calvarial zone
without bone (area, 3.8 to 7.5 centimetersquare; median area 4.2
centimetersquare) following the resection of pathological skull region with an
inner table of horizontally split adjacent skull site in thirty-six patients
(aged between 28 and 125 months; median age, 68.75 months, minimum follow-up 14
months). The donor site, the characteristics of skin incision such as length,
shape, location and bone splitting technique were determined based on our
treatment algorithm for "8 cranioplasty". Pre- and postoperative clinical
outcomes and courses as well as radiological results are documented. RESULTS:
Mean follow-up period for all children was 25 months. There was no mortality and
5.55% morbidity (n=2: 1 sterile wound dehiscence and 1 sterile wound discharge).
No infected flap was seen and none of the patients required a second surgery. No
graft failure, tumor recurrence or residue occurred. CONCLUSION: Almost all of
our patients reported good surgical and clinical outcomes with this presented
management and surgical algorithm. Autologous split bone grafting technique in
small-size skull defects, with its proposed name "8 cranioplasty" is a safe and
effective reconstructive procedure due to its short-term surgery, small-size
surgical zone, low complication rate, good cosmetic results and cost
effectiveness. In addition, our algorithm specified for this procedure is
purposive and also saves the surgeon time in the surgical planning stage.
PMID- 27509460
TI - Bilateral Thalamic Edema from Coexisting Choroid Plexus Arteriovenous
Malformation and Sinus Thrombosis: Case Report.
AB - Bilateral thalamic dysfunction secondary to venous congestion may result from
either venous sinus thrombosis or high flow arteriovenous malformations or a
combination of both. We present a case of bilateral thalamic edema resulting from
concomitant choroid plexus arteriovenous malformation (AVM) and straight sinus
thrombosis and describe our treatment approach. The patient presented with
several weeks of progressive confusion and memory deficits. Magnetic resonance
imaging and venography (MRI/ MRV) showed bilateral thalamic T2 hyperintensities
and straight sinus thrombosis. Subsequent cerebral angiography revealed a choroid
plexus AVM within the right lateral ventricle. The patient underwent surgical
resection of the AVM resulting in postoperative resolution of bilateral thalamic
edema on MRI and improvement of his confusion and memory deficits. This case
demonstrates a rare example of reversible bilateral thalamic edema secondary to
venous hypertension from both an AVM and sinus occlusion after appropriate
treatment of the AVM.
PMID- 27509461
TI - Surgical Strategies and Functional Outcome of Intramedullary Cervicomedullary
Ependymoma.
AB - AIM: To evaluate the surgical strategies and functional outcomes of
intramedullary cervicomedullary ependymoma (ICE). MATERIAL AND METHODS: The
authors retrospectively reviewed the clinical and imaging data of 28 ICE patients
who underwent surgical resection, including 11 males and 17 females and the
average age was 37.9 years (range:11-69 years). The modified McCormick grading
system (mMG) was used to evaluate the neurological functions before surgery, at
discharge and at long-term follow-up. RESULTS: Gross total resections (GTRs) were
performed in 21 patients (75.0%), and subtotal resections (STRs) were achieved in
the other 7 patients (25.0%). An ill-defined tumor border was a significant
factor leading to STR (p=0.026). At discharge, the mMG improved in 11 patients
(39.3%), stabilized in 14 (50.0%), and worsened in 3 (10.7%). The 3 patients with
deterioration were all in the STR Group and the neurological deterioration rate
was significantly higher in the STR Group than that in the GTR Group (p=0.011).
The follow-up period ranged from 9 to 77 months (mean 49.6+/-26.9 months). Two
patients (7.1%) had tumor recurrence during this period. The long-term follow-up
mMG was improved in 25 patients (89.3%), stabilized in 3 (10.7%), and no one
worsened, compared with preoperative mMG. CONCLUSION: GTR of ICE could be
achieved in majority of patients, especially for those with well-defined tumor
boundaries. GTR lead to a better outcome in the short term after surgery. A
favorable functional outcome could be achieved for most ICE patients in the long
term.
PMID- 27509462
TI - Predictive Role of External Carotid Artery Vasospasm on Cerebral Ischemia After
Subarachnoid Hemorrhage: Experimental Study.
AB - AIM: Cerebral vasospasm after subarachnoid hemorrhage (SAH) may lead to a
devastating neurological outcome by inducing cerebral ischemia. However the role
of external carotid artery (ECA) vasospasm has been rarely reported in the
literature. The aim of this study was to elucidate the effect of ECA vasospasm on
cerebral ischemia related neurodegeneration in the cerebral cortex after SAH.
MATERIAL AND METHODS: This study was performed on 23 rabbits, divided into three
groups: control (n=5), sham (n=5), and SAH (n=13). Experimental SAH was performed
by injecting 0.75 mL auricular arterial homologous blood into the cisterna magna.
After three weeks, the animals were decapitated and the common carotid arteries
with their external and internal branches and the brains were examined
histopathologically. Vasospasm indexes (VSI) of ECAs and internal carotid
arteries (ICAs) and degenerated glial cell numbers of temporal cortices (n/mm3)
were estimated stereologically and the results were compared statistically.
RESULTS: Temporal cortex glial cell density was estimated as 136.950+/-9.257/mm3
in normal rabbits, 131.324+/-7.987/mm3 in sham, 112.320+/-6.112/mm3 in light, and
97.543+/-5.432/mm3 in severe ECA vasospasm. The mean VSI values of ECA of all
groups were 1.95+/-0.21, 2.15+/-0.29, 2.95+/-0.65 and 3.12+/-0.276, respectively.
Statistical differences between the VSI values of ECA and degenerated neuron
densities in temporal cortices were significant (p < 0.005). CONCLUSION: ECA
vasospasm was observed to have a more important predictive role on the serious
cerebral ischemia and neuronal degeneration after SAH. The mechanism may be
related to ischemia of the parasympathetic ganglia of the lower cranial nerves
and dorsal root ganglion.
PMID- 27509463
TI - Pterional and Unifrontal Approaches for the Microsurgical Resection of Olfactory
Groove Meningiomas: Experience with 61 Consecutive Patients.
AB - AIM: Olfactory groove meningiomas make up 4 to 13% of meningiomas. The first line
treatment of meningiomas is surgery, but the extent and types of approaches
advised for olfactory groove meningiomas are diverse, from aggressive skull base
approaches to standard or minimally invasive craniotomies and endoscopic
approaches. We retrospectively reviewed our series of olfactory groove
meningiomas that were operated microsurgically by standard pterional or
unifrontal approaches. MATERIAL AND METHODS: Our series of 61 olfactory groove
meningioma patients operated through pterional or unifrontal approaches between
March 1987 and September 2015 was reviewed and the clinical data, radiological
findings, surgical treatment and clinical outcomes of the patients were
retrospectively analyzed. RESULTS: Sixty-three craniotomies were performed in
total. Pterional and unifrontal approaches were used in 38 (60.3%) and 25 (39.7%)
surgical procedures, respectively. Overall, gross total tumor resection was
achieved in 59 (93.7%) cases. Complications were seen in 8 cases, and 2 of these
patients underwent reoperation. Three of the 4 patients where only subtotal
resection could be achieved underwent gamma knife radiosurgery. CONCLUSION:
Pterional and unifrontal approaches, which are familiar and standard for
neurosurgeons, can accomplish high rates of total resection with acceptable
complication and recurrence rates for the treatment of olfactory groove
meningiomas.
PMID- 27509464
TI - Resveratrol Treatment Prevents Hippocampal Neurodegeneration in a Rodent Model of
Traumatic Brain Injury.
AB - AIM: Traumatic brain injury (TBI) is a complex process. Increasing evidence has
demonstrated that reactive oxygen species contribute to brain injury. Resveratrol
(RVT) which exhibits significant antioxidant properties, is neuroprotective
against excitotoxicity, ischemia, and hypoxia. The aim of this study was to
evaluate the neuroprotective effects of RVT on the hippocampus of a rat model of
TBI. MATERIAL AND METHODS: Twenty eight rats were divided into four groups. A
moderate degree of head trauma was induced using Feeney"s falling weight
technique. Group 1 (control) underwent no intervention or treatment. Head trauma
was induced in Group 2 (trauma) and no drug was administered. Head trauma was
induced in Group 3 and low-dose RVT (50 mg/kg per day) was injected. In Group 4,
high-dose RVT (100 mg/kg per day) was used after head trauma. Brain tissues were
extracted immediately after perfusion without damaging the tissues.
Histopathological and biochemistry parameters were studied. RESULTS: Brain tissue
malondialdehyde (MDA) levels in the trauma group were significantly higher than
those in the control, lowdose RVT-treated, and high-dose-RVT-treated groups. The
superoxide dismutase (SOD) levels in the control group were significantly higher
than those in the trauma, low-dose RVT-treated, and high-dose RVT-treated groups.
Glutathione peroxidase (GSH-Px) levels in the control group were significantly
higher than those in the trauma and low-dose RVT-treated groups. The level of
oxidative deoxyribonucleic acid (DNA) damage (8-OHdG/106 dG) in the trauma group
was higher than that in the control group, low-dose RVT-treated, and high-dose
RVT-treated groups. CONCLUSION: Resveratrol has a healing effect on neurons after
TBI.
PMID- 27509465
TI - Does Surgery for Adult Spinal Deformity Affect the Cognitive Abilities in
Patients over 50 Years of Age?
AB - AIM: To analyze the cognitive abilities of older patients undergoing spinal
deformity surgery so as to understand whether adult spinal deformity (ASD)
surgery is associated with postoperative cognitive malfunction. MATERIAL AND
METHODS: A prospective longitudinal study was performed on surgical patients
older than 50 years, enrolled in a prospective multicenter database. Mini-mental
state examination (MMSE) was performed to assess cognitive function in addition
to the health-related quality of life (HRQOL) tests; (SF-36, ODI and SRS-22) at
the pre-operative, post-operative 6 weeks and 6 months points. Demographics,
preoperative health status, co-morbidities and surgical characteristics were also
analyzed. Descriptive statistics and repeated measures of variance analysis were
performed. RESULTS: A total of 90 patients with a mean age of 67.4+/-8.2 years
were enrolled in the study; all had MMSE evaluations at 6 weeks follow-up and 58
patients had both 6 weeks and 6 months follow-up. Average (SD) surgical time,
estimated blood loss, number of levels fused and hospital stay were 240.1 (111.9)
minutes, 1621.2 (1058.7) ml, 11.2 (4.4) levels and 14.2 (11.45) days,
respectively. On analysis, a slight increase in mean MMSE score (p > 0.05)
between time points was found despite decreases of > 2 points (3 or 4) in 6
patients (6.7%) at both time points. CONCLUSION: Although ASD surgery in older
patients is recognized as challenging, this study suggests that it is not
necessarily associated with a significant deterioration in the cognitive
abilities of patients undergoing surgery. This may be due to the relatively minor
influence of ASD itself on the cognitive abilities of the patients involved as
well as to the relatively stable hemodynamic conditions obtainable during modern
ASD surgery.
PMID- 27509466
TI - Endoscopic ultrasound-guided gastrojejunostomy with a Nagi stent for relief of
jejunal loop obstruction following hepaticojejunostomy.
PMID- 27509467
TI - Unsuspected cervical osteophytes and complex endoscopy: there is cause for
concern!
PMID- 27509468
TI - Adenomyoma of the common bile duct: a rare lesion diagnosed and treated by ERCP.
PMID- 27509469
TI - Endoscopic gastroesophageal mucosal flap valvuloplasty with anti-reflux
potential.
PMID- 27509470
TI - The use of stand-alone fully covered self-expandable metallic stents for drainage
of walled-off necrosis or pseudocyst may lead to poor results.
PMID- 27509471
TI - Proximal esophageal cancer missed during esophagogastroduodenoscopy: should the
detection of an inlet patch be added to the quality criteria for upper
gastrointestinal endoscopy?
PMID- 27509472
TI - A new method of polyglycolic acid sheet placement in the stomach after endoscopic
submucosal dissection.
PMID- 27509473
TI - Endoscopic ultrasound-guided pancreaticogastrostomy using a lumen-apposing metal
stent plus a double-pigtail plastic stent.
PMID- 27509474
TI - An unforeseeable adverse event during ERCP.
PMID- 27509475
TI - Single-operator pancreatoscopy with electrohydraulic lithotripsy of large
pancreatic duct stones in post-Whipple anatomy.
PMID- 27509476
TI - Fibronectin adsorption on osteoconductive hydroxyapatite and non-osteoconductive
alpha-alumina.
AB - The osteoconductivity mechanism of hydroxyapatite (HAp) has not been elucidated.
It is hypothesized that specific proteins adsorb on HAp, promoting its
osteoconductivity. To verify this hypothesis, we compared the adsorption behavior
of fibronectin (Fn) on HAp powder and on alpha-alumina (alpha-Al2O3) powder, a
material with no osteoconductivity. More Fn adsorbed on alpha-Al2O3 than on HAp,
irrespective of the Fn concentration, and there was no significant difference in
the secondary structure of Fn adsorbed on HAp and alpha-Al2O3. Further, it is
possible that Fn did not adsorb on HAp and alpha-Al2O3 through the Arg-Gry-Asp
motif of Fn. The amount of Fn adsorbed on HAp oriented to the a(b)-axis with very
little decrease in carbonate and the adsorbed Fn had a smaller alpha-helix
structure content. The results suggest that the secondary and/or higher-order
structure rather than the amount of adsorbed Fn might affect the
osteoconductivity of HAp, which might be electrostatically controlled by the
crystal face orientation and/or carbonate content of HAp, although this should be
confirmed by a cell culture test in the future.
PMID- 27509478
TI - Pharmacogenetics of efavirenz discontinuation for reported central nervous system
symptoms appears to differ by race.
AB - BACKGROUND: Efavirenz frequently causes central nervous system (CNS) symptoms. We
evaluated genetic associations with efavirenz discontinuation for CNS symptoms
within 12 months of treatment initiation. METHODS: Patients had initiated
efavirenz-containing regimens at an HIV primary care clinic in the Southeastern
United States and had at least 12 months of follow-up data. Polymorphisms in
CYP2B6 and CYP2A6 defined efavirenz metabolizer categories. Genome-wide
genotyping enabled adjustment for population stratification. RESULTS: Among 563
evaluable patients, 99 (17.5%) discontinued efavirenz within 12 months, 29 (5.1%)
for CNS symptoms. The hazard ratio (HR) for efavirenz discontinuation for CNS
symptoms in slow versus extensive metabolizers was 4.9 [95% confidence interval
(CI): 1.9-12.4; P=0.001]. This HR in Whites was 6.5 (95% CI: 2.3-18.8; P=0.001)
and 2.6 in Blacks (95% CI: 0.5-14.1; P=0.27). Considering only slow metabolizers,
the HR in Whites versus Blacks was 3.1 (95% CI: 0.9-11.0; P=0.081). The positive
predictive value of slow metabolizer genotypes for efavirenz discontinuation was
27% in Whites and 11% in Blacks. CONCLUSION: Slow metabolizer genotypes were
associated significantly with efavirenz discontinuation for reported CNS
symptoms. This association was considerably stronger in Whites than in Blacks.
PMID- 27509480
TI - Ionic Liquid-Assisted Electropolymerization for Lithographical Perfluorocarbon
Deposition and Hydrophobic Patterning.
AB - We developed a novel approach for hydrophobic patterning: combining the
photolithography technique with ionic-liquid (IL)-based electropolymerization to
fabricate a hydrophobic pattern. Perfluoro-functionalized 3,4
ethylenedioxythiophene (EDOT-F) dispersed in ILs was directly electropolymerized
on substrates, which were patterned in advance with positive photoresists. The
positive photoresists did not dissolve in ionic liquids during the
electropolymerization process, and the poly(EDOT-F) film created hydrophobic
domains, which resulted in hydrophobic patterning. This approach provides desired
patterns with a lateral resolution consistent with the mask for photolithography.
Two kinds of modified indium-tin-oxide-coated glass (ITO-glass) substrates were
used to demonstrate the feasibility of process for creating a hydrophobic
pattern: ITO-glass substrates coated with nanostructured PEDOT, and the same
substrates coated with Au nanoparticles. By confining water droplets on these two
patterned substrates to form droplet arrays, we demonstrated two potential
applications: multiple droplet-type electrochemical cells and surface-enhanced
Raman scattering platforms. In addition, we also applied this approach to create
hydrophobic patterning on ITO-coated polyethylene terephthalate (ITO-PET)
substrates. The droplet arrays remained well-organized on the ITO-PET substrates
even when the substrates were bent. Our work successfully introduced ILs into the
photolithography process, implying great potential for these green solvents.
PMID- 27509479
TI - Mild leg length discrepancy affects lower limbs, pelvis and trunk biomechanics of
individuals with knee osteoarthritis during gait.
AB - BACKGROUND: Leg length discrepancy greater than 1cm increases odds of progressive
knee osteoarthritis in the shorter limb. METHODS: Biomechanical data of 15 knee
osteoarthritis participants were collected while they walked under two
conditions: (1) control - wearing thick sandals; (2) short limb - wearing a thin
sandal on the osteoarthritic limb and a thick sandal on the contralateral limb.
The thick and thin sandals had 1.45cm of thickness difference. The knee
osteoarthritis limb was analyzed for both conditions. Ankle, knee, hip, pelvis
and trunk kinematics and moments were measured with a motion and force capture
system. Principal component analysis and mean hypothesis' tests were used to
compare the conditions. FINDINGS: The short limb condition reduced rearfoot
plantarflexion in loading response and increased plantarflexion in late stance
(p<0.001), increased ankle dorsiflexion moment (p=0.003), increased knee flexion
angle in loading response and delayed knee flexion in late stance (p=0.001),
increased knee extension moment in loading response and increased knee flexion
moment in terminal stance (p=0.023), reduced hip extension moment in early stance
and reduced hip flexion moment in late stance (p<0.001), reduced knee adduction
moment (p=0.015), reduced hip adduction angle (p=0.001) and moment (p=0.012) and
increased pelvic (p=0.023) and trunk (p=0.001) external rotation. INTERPRETATION:
Mild leg length discrepancy affects the entire kinetic chain of individuals with
knee osteoarthritis during gait, increasing knee sagittal plane loading, which
helps to explain why mild leg length discrepancy accelerates knee osteoarthritis
progression. Mild leg length discrepancy should not be overlooked in knee
osteoarthritis individuals.
PMID- 27509481
TI - Risk factors for pancreatitis after posterior spinal fusion in children with
cerebral palsy.
AB - This study reports on the prevalence and risk factors of acute pancreatitis after
posterior spinal fusion for cerebral palsy scoliosis. Pancreatitis diagnosis was
based on elevated amylase or lipase above three times the upper normal limit.
Perioperative data were compared between patients with and without pancreatitis.
We included 300 patients; 55% developed acute pancreatitis. Gastrostomy
dependence was more common in the pancreatitis group (P=0.048). Perioperative
data were similar between groups. Patients with pancreatitis had longer duration
of hospitalization (19 vs. 13 days, P<0.001). Acute pancreatitis is common after
cerebral palsy scoliosis surgery. Gastrostomy dependence increases its risk.
Although no mortality was reported, hospital stay was longer.
PMID- 27509482
TI - Bilateral femoral neck fractures associated with complex pelvic ring injuries in
a pediatric patient: a case report.
AB - : Femoral neck and pelvic fractures are rarely encountered in the pediatric
population secondary to the resilient nature of the immature skeleton. Both
fracture types usually result from high-energy blunt trauma including motor
vehicle collisions, motor vehicle-pedestrian accidents, and falls from height.
Considerable studies have been published on the natural history, management, and
complications of pediatric pelvis and femoral neck fractures. However, few case
reports have documented both fracture types in the same patient. Management of
concomitant injuries presents unique challenges both for operative stabilization
and for clinical postoperative care. After appropriate consent was obtained, a
thorough review was performed of the patient's hospital records and imaging
history. The senior author of the report also provided insight into the
management of the patient's initial injuries and subsequent complications. Our
case involves a 4-year-old female who was overrun by an all-terrain vehicle. Her
orthopedic injuries included a nondisplaced Delbet type 3 fracture of the right
femoral neck, a completely displaced Delbet type 3 fracture of the left femoral
neck, bilateral sacroiliac fracture-dislocations, severe comminution of her left
pubic rami, and a free-floating right pubic rami segment spanning from the
triradiate cartilage to the pubic symphysis with severe rotational deformity. Her
postoperative recovery was complicated by refracture of her left femoral neck
(Delbet type 1), left hip osteomyelitis, and left femoral head avascular
necrosis. The salient features of her operative management, subsequent
complications, and functional recovery are described in this report. Cases of
bilateral femoral neck fractures and multiple pelvic fractures in pediatric
patients are sparsely documented in the literature because of their infrequent
occurrence. Pediatric pelvic fractures typically do well with conservative
treatment secondary to the incredible remodeling ability of the immature pelvis.
Femoral neck fractures, in contrast, are highly associated with complications
including coxa vara, nonunion, infection, physeal closure, and avascular
necrosis. This case report documents two rare fracture types in the same patient
and describes the challenges encountered throughout the duration of her recovery.
LEVEL OF EVIDENCE: Level V, Case report.
PMID- 27509483
TI - Recurrent Bacille Calmette-Guerin osteomyelitis with ankle joint involvement in a
toddler: gait analysis and rehabilitation experience.
AB - Bacille Calmette-Guerin (BCG) osteomyelitis is a rare complication after
vaccination. This article reports on a 1-year-old immunocompetent boy with
recurrent BCG osteomyelitis involving the distal tibia who presented with a
limping gait from the beginning of toddling. The lesion was located in the
metaphysis and crossed the growth plate to the epiphysis, causing concern for
ambulation. After surgery, he was initiated on an individualized, intense
rehabilitation program and achieved a good functional recovery. Rehabilitation
programs with gait analyses provide effective therapeutic and monitoring methods
for toddlers recovering from BCG osteomyelitis.
PMID- 27509484
TI - Clinical application of back surface topography by means of structured light in
the screening of idiopathic scoliosis.
AB - We present the results of the clinical validity in the screening of idiopathic
scoliosis with a nonharming method of back surface topography by means of
structured light projection. A total of 155 patients were evaluated (mean age
13.3 years). They were divided into two groups: pathologic patients (scoliosis)
and nonpathologic patients (control and asymmetries). An analytical case-control
study was carried out. Our topographic method obtained 92% sensitivity and 74%
specificity as a screening test in identifying patients with scoliosis (P=0.05).
We could quantify the vertebral deformity of scoliosis in the three spatial
planes by means of three topographic variables, Horizontal Plane Deformity Index,
Posterior Trunk Symmetry Index and Columnar Profile, and to elaborate a combined
screening algorithm with good reliability parameters.
PMID- 27509485
TI - Spontaneous healing of fractures and osteotomy within intercalary allograft
reconstruction after distal femur osteosarcoma resection in a child.
AB - Intercalary biologic reconstructions using allogenic bone grafts remain a useful
option in orthopedic oncology; however, these reconstructions are prone to
fractures, and treatment is usually required involving surgical interventions.
Biologic activity of the implanted allografts remains minimal, but in some cases,
spontaneous healing of the graft may occur. We present a report and discussion on
two fractures and corrective osteotomy within the implanted allograft that healed
with abundant callus without the need for additional surgery. In selected
patients, allograft incorporation can be completed to a degree allowing for its
biologic activity and spontaneous healing of fractures or osteotomy.
PMID- 27509486
TI - Enrichment of enzymatically mineralized gellan gum hydrogels with phlorotannin
rich Ecklonia cava extract Seanol((r)) to endow antibacterial properties and
promote mineralization.
AB - Hydrogels offer several advantages as biomaterials for bone regeneration,
including ease of incorporation of soluble substances such as mineralization
promoting enzymes and antibacterial agents. Mineralization with calcium phosphate
(CaP) increases bioactivity, while antibacterial activity reduces the risk of
infection. Here, gellan gum (GG) hydrogels were enriched with alkaline
phosphatase (ALP) and/or Seanol((r)), a seaweed extract rich in phlorotannins
(brown algae-derived polyphenols), to induce mineralization with CaP and increase
antibacterial activity, respectively. The sample groups were unmineralized
hydrogels, denoted as GG, GG/ALP, GG/Seanol and GG/Seanol/ALP, and hydrogels
incubated in mineralization medium (0.1 M calcium glycerophosphate), denoted as
GG/ALP_min, GG/Seanol_min and GG/Seanol/ALP_min. Seanol((r)) enhanced
mineralization with CaP and also increased compressive modulus. Seanol((r)) and
ALP interacted in a non-covalent manner. Release of Seanol((r)) occurred in a
burst phase and was impeded by ALP-mediated mineralization. Groups GG/Seanol and
GG/ALP/Seanol exhibited antibacterial activity against methicillin-resistant
Staphylococcus aureus. GG/Seanol/ALP_min, but not GG/Seanol_min, retained some
antibacterial activity. Eluates taken from groups GG/ALP_min, GG/Seanol_min and
GG/ALP/Seanol_min displayed comparable cytotoxicity towards MG-63 osteoblast-like
cells. These results suggest that enrichment of hydrogel biomaterials with
phlorotannin-rich extracts is a promising strategy to increase mineralizability
and antibacterial activity.
PMID- 27509487
TI - Residential proximity to environmental pollution sources and risk of rare tumors
in children.
AB - BACKGROUND: Few epidemiologic studies have explored risk factors for rare tumors
in children, and the role of environmental factors needs to be assessed.
OBJECTIVES: To ascertain the effect of residential proximity to both industrial
and urban areas on childhood cancer risk, taking industrial groups into account.
METHODS: We conducted a population-based case-control study of five childhood
cancers in Spain (retinoblastoma, hepatic tumors, soft tissue sarcomas, germ cell
tumors, and other epithelial neoplasms/melanomas), including 557 incident cases
from the Spanish Registry of Childhood Tumors (period 1996-2011), and 3342
controls individually matched by year of birth, sex, and region of residence.
Distances were computed from the residences to the 1271 industries and the 30
urban areas with >=75,000 inhabitants located in the study area. Using logistic
regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for
categories of distance to industrial and urban pollution sources were calculated,
with adjustment for matching variables and socioeconomic confounders. RESULTS:
Children living near industrial and urban areas as a whole showed no excess risk
for any of the tumors analyzed. However, isolated statistical associations (OR;
95%CI) were found between retinoblastoma and proximity to industries involved in
glass and mineral fibers (2.49; 1.01-6.12 at 3km) and organic chemical industries
(2.54; 1.10-5.90 at 2km). Moreover, soft tissue sarcomas registered the lower
risks in the environs of industries as a whole (0.59; 0.38-0.93 at 4km).
CONCLUSIONS: We have found isolated statistical associations between
retinoblastoma and proximity to industries involved in glass and mineral fibers
and organic chemical industries.
PMID- 27509488
TI - Diversity of Human and Macaque Airway Immune Cells at Baseline and during
Tuberculosis Infection.
AB - Immune cells of the distal airways serve as "first responders" of host immunity
to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of
cynomolgus macaques recapitulates the range of human outcomes from clinically
silent latent tuberculosis infection (LTBI) to active tuberculosis of various
degrees of severity. To further advance the application of this model to human
studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and
cynomolgus macaques before and after Mtb infection. A simple gating strategy
effectively defined BAL T-cell and phagocyte populations in both species. BAL
from Mtb-naive humans and macaques showed similar differential cell counts. BAL T
cells of macaques were composed of fewer CD4+cells but more CD8+ and CD4+CD8+
double-positive cells than were BAL T cells of humans. The most common
mononuclear phagocyte population in BAL of both species displayed coexpression of
HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying
only some of these markers were observed as well. Macaques with LTBI displayed a
marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques,
the prevalence of specific mononuclear phagocyte subsets in baseline BAL
correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active
disease). Overall, these findings demonstrate the comparability of studies of
pulmonary immunity to Mtb in humans and macaques. They also indicate a previously
undescribed complexity of airway mononuclear phagocyte populations that suggests
further lines of investigation relevant to understanding the mechanisms of both
protection from and susceptibility to the development of active tuberculosis
within the lung.
PMID- 27509489
TI - Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA
Receptor Antagonists.
AB - Enantiopure tryptophanol is easily obtained from the reduction of its parent
natural amino acid trypthophan (available from the chiral pool), and can be used
as chiral auxiliary/inductor to control the stereochemical course of a
diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for
the syntheses of natural products or biological active molecules containing the
aminoalcohol functionality. In this communication, we report the development of a
small library of indolo[2,3-a]quinolizidines and evaluation of their activity as
N-Methyl d-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine
scaffold was obtained using the following key steps: (i) a stereoselective
cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic delta
oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The
synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA
receptor antagonists and one compound was identified to be 2.9-fold more potent
as NMDA receptor blocker than amantadine (used in the clinic for Parkinson's
disease). This compound represents a hit compound for the development of novel
NMDA receptor antagonists with potential applications in neurodegenerative
disorders associated with overactivation of NMDA receptors.
PMID- 27509490
TI - Glutamine Synthetase Drugability beyond Its Active Site: Exploring
Oligomerization Interfaces and Pockets.
AB - BACKGROUND: Glutamine synthetase (GS) is a crucial enzyme to the nitrogen cycle
with great commercial and pharmaceutical value. Current inhibitors target the
active site, affecting GS activity indiscriminately in all organisms. As the
active site is located at the interface between two monomers, the protein-protein
interface (PPI) of GSs gains a new role, by providing new targets for enzyme
inhibition. Exploring GSs PPI could allow for the development of inhibitors
selective for specific organisms. Here we map the PPI of three GSs-human (hsGS),
maize (zmGS) and Mycobacterium tuberculosis (mtGS)-and unravel new drugable
pockets. METHODS: The PPI binding free energy coming from key residues on three
GSs from different organisms were mapped by computational alanine scan
mutagenesis, applying a multiple dielectric constant MM-PBSA methodology. The
most relevant residues for binding are referred as hot-spots. Drugable pockets on
GS were detected with the Fpocket software. RESULTS AND CONCLUSIONS: A total of
23, 19 and 30 hot-spots were identified on hsGS, zmGS and mtGS PPI. Even
possessing differences in the hot-spots, hsGS and zmGS PPI are overall very
similar. On the other hand, mtGS PPI differs greatly from hsGS and zmGS PPI. A
novel drugable pocket was detected on the mtGS PPI. It seems particularly
promising for the development of selective anti-tuberculosis drugs given its
location on a PPI region that is highly populated with hot-spots and is
completely different from the hsGS and zmGS PPIs. Drugs targeting this pockets
should be inactive on eukaryotic GS II enzymes.
PMID- 27509491
TI - New Sesquiterpenenoids from Ainsliaea yunnanensis.
AB - Investigation of the ethanol extract of the whole plant of Ainsliaea yunnanensis
led to the isolation of four new dimeric sesquiterpene lactones, ainsliadimer F-I
(1-4), together with seven known dimeric sesquiterpene lactones (5-11) and ten
sesquiterpenes (12-21). Their structures were elucidated by spectroscopic
methods. The relative stereochemistry of ainsliadimer F was further confirmed by
single crystal X-ray diffraction analysis. Compounds 1-21 were tested for the
inhibition of nuclear factor kappa B (NF-kappaB) in the 293-NF-kappaB-luciferase
reporter cell line induced by lipopolysaccharide (LPS), and Compounds 5, 18, 20
and 21 were further tested for the production of TNF-alpha, IL-1beta, IL-6 and IL
10 in RAW 264.7 macrophages induced by LPS. Compounds 5, 18, 20 and 21 exhibited
significant activity in anti-inflammatory activity assays.
PMID- 27509492
TI - MicroRNA-155 Mediates Augmented CD40 Expression in Bone Marrow Derived
Plasmacytoid Dendritic Cells in Symptomatic Lupus-Prone NZB/W F1 Mice.
AB - Systemic lupus erythematosus (SLE) is a chronic multi-organ autoimmune disease
characterized by hyperactivated immune responses to self-antigens and persistent
systemic inflammation. Previously, we reported abnormalities in circulating and
bone marrow (BM)-derived plasmacytoid dendritic cells (pDCs) from SLE patients.
Here, we aim to seek for potential regulators that mediate functional aberrations
of pDCs in SLE. BM-derived pDCs from NZB/W F1 mice before and after the disease
onset were compared for toll-like receptor (TLR) induced responses and microRNA
profile changes. While pDCs derived from symptomatic mice were phenotypically
comparable to pre-symptomatic ones, functionally they exhibited hypersensitivity
to TLR7 but not TLR9 stimulation, as represented by the elevated upregulation of
CD40, CD86 and MHC class II molecules upon R837 stimulation. Upregulated
induction of miR-155 in symptomatic pDCs following TLR7 stimulation was observed.
Transfection of miR-155 mimics in pre-symptomatic pDCs induced an augmented
expression of Cd40, which is consistent with the increased CD40 expression in
symptomatic pDCs. Overall, our results provide evidence for miR-155-mediated
regulation in pDC functional abnormalities in SLE. Findings from this study
contribute to a better understanding of SLE pathogenesis and ignite future
interests in evaluating the molecular regulation in autoimmunity.
PMID- 27509493
TI - Zeb1 Is a Potential Regulator of Six2 in the Proliferation, Apoptosis and
Migration of Metanephric Mesenchyme Cells.
AB - Nephron progenitor cells surround around the ureteric bud tips (UB) and
inductively interact with the UB to originate nephrons, the basic units of renal
function. This process is determined by the internal balance between self-renewal
and consumption of the nephron progenitor cells, which is depending on the
complicated regulation networks. It has been reported that Zeb1 regulates the
proliferation of mesenchymal cells in mouse embryos. However, the role of Zeb1 in
nephrons generation is not clear, especially in metanephric mesenchyme (MM).
Here, we detected cell proliferation, apoptosis and migration in MM cells by EdU
assay, flow cytometry assay and wound healing assay, respectively. Meanwhile,
Western and RT-PCR were used to measure the expression level of Zeb1 and Six2 in
MM cells and developing kidney. Besides, the dual-luciferase assay was conducted
to study the molecular relationship between Zeb1 and Six2. We found that knock
down of Zeb1 decreased cell proliferation, migration and promoted cell apoptosis
in MM cells and Zeb1 overexpression leaded to the opposite data. Western-blot and
RT-PCR results showed that knock-down of Zeb1 decreased the expression of Six2 in
MM cells and Zeb1 overexpression contributed to the opposite results. Similarly,
Zeb1 promoted Six2 promoter reporter activity in luciferase assays. However,
double knock-down of Zeb1 and Six2 did not enhance the apoptosis of MM cells
compared with control cells. Nevertheless, double silence of Zeb1 and Six2
repressed cell proliferation. In addition, we also found that Zeb1 and Six2 had
an identical pattern in distinct developing phases of embryonic kidney. These
results indicated that there may exist a complicated regulation network between
Six2 and Zeb1. Together, we demonstrate Zeb1 promotes proliferation and apoptosis
and inhibits the migration of MM cells, in association with Six2.
PMID- 27509495
TI - A Wireless Sensor Network with Soft Computing Localization Techniques for Track
Cycling Applications.
AB - In this paper, we propose two soft computing localization techniques for wireless
sensor networks (WSNs). The two techniques, Neural Fuzzy Inference System (ANFIS)
and Artificial Neural Network (ANN), focus on a range-based localization method
which relies on the measurement of the received signal strength indicator (RSSI)
from the three ZigBee anchor nodes distributed throughout the track cycling
field. The soft computing techniques aim to estimate the distance between
bicycles moving on the cycle track for outdoor and indoor velodromes. In the
first approach the ANFIS was considered, whereas in the second approach the ANN
was hybridized individually with three optimization algorithms, namely Particle
Swarm Optimization (PSO), Gravitational Search Algorithm (GSA), and Backtracking
Search Algorithm (BSA). The results revealed that the hybrid GSA-ANN outperforms
the other methods adopted in this paper in terms of accuracy localization and
distance estimation accuracy. The hybrid GSA-ANN achieves a mean absolute
distance estimation error of 0.02 m and 0.2 m for outdoor and indoor velodromes,
respectively.
PMID- 27509494
TI - beta-Ketoacyl-acyl Carrier Protein Synthase I (KASI) Plays Crucial Roles in the
Plant Growth and Fatty Acids Synthesis in Tobacco.
AB - Fatty acids serve many functions in plants, but the effects of some key genes
involved in fatty acids biosynthesis on plants growth and development are not
well understood yet. To understand the functions of 3-ketoacyl-acyl-carrier
protein synthase I (KASI) in tobacco, we isolated two KASI homologs, which we
have designated NtKASI-1 and NtKASI-2. Expression analysis showed that these two
KASI genes were transcribed constitutively in all tissues examined. Over
expression of NtKASI-1 in tobacco changed the fatty acid content in leaves,
whereas over-expressed lines of NtKASI-2 exhibited distinct phenotypic features
such as slightly variegated leaves and reduction of the fatty acid content in
leaves, similar to the silencing plants of NtKASI-1 gene. Interestingly, the
silencing of NtKASI-2 gene had no discernibly altered phenotypes compared to wild
type. The double silencing plants of these two genes enhanced the phenotypic
changes during vegetative and reproductive growth compared to wild type. These
results uncovered that these two KASI genes had the partially functional
redundancy, and that the KASI genes played a key role in regulating fatty acids
synthesis and in mediating plant growth and development in tobacco.
PMID- 27509496
TI - Novel Low-Cost Sensor for Human Bite Force Measurement.
AB - This paper presents the design and development of a low cost and reliable maximal
voluntary bite force sensor which can be manufactured in-house by using an
acrylic laser cutting machine. The sensor has been designed for ease of
fabrication, assembly, calibration, and safe use. The sensor is capable of use
within an hour of commencing production, allowing for rapid
prototyping/modifications and practical implementation. The measured data shows a
good linear relationship between the applied force and the electrical resistance
of the sensor. The output signal has low drift, excellent repeatability, and a
large measurable range of 0 to 700 N. A high signal-to-noise response to human
bite forces was observed, indicating the high potential of the proposed sensor
for human bite force measurement.
PMID- 27509497
TI - Spatiotemporal Interpolation for Environmental Modelling.
AB - A variation of the reduction-based approach to spatiotemporal interpolation
(STI), in which time is treated independently from the spatial dimensions, is
proposed in this paper. We reviewed and compared three widely-used spatial
interpolation techniques: ordinary kriging, inverse distance weighting and the
triangular irregular network. We also proposed a new distribution-based distance
weighting (DDW) spatial interpolation method. In this study, we utilised one year
of Tasmania's South Esk Hydrology model developed by CSIRO. Root mean squared
error statistical methods were performed for performance evaluations. Our results
show that the proposed reduction approach is superior to the extension approach
to STI. However, the proposed DDW provides little benefit compared to the
conventional inverse distance weighting (IDW) method. We suggest that the
improved IDW technique, with the reduction approach used for the temporal
dimension, is the optimal combination for large-scale spatiotemporal
interpolation within environmental modelling applications.
PMID- 27509498
TI - A Fluidically Tunable Metasurface Absorber for Flexible Large-Scale Wireless
Ethanol Sensor Applications.
AB - In this paper, a novel flexible tunable metasurface absorber is proposed for
large-scale remote ethanol sensor applications. The proposed metasurface absorber
consists of periodic split-ring-cross resonators (SRCRs) and microfluidic
channels. The SRCR patterns are inkjet-printed on paper using silver nanoparticle
inks. The microfluidic channels are laser-etched on polydimethylsiloxane (PDMS)
material. The proposed absorber can detect changes in the effective permittivity
for different liquids. Therefore, the absorber can be used for a remote chemical
sensor by detecting changes in the resonant frequencies. The performance of the
proposed absorber is demonstrated with full-wave simulation and measurement
results. The experimental results show the resonant frequency increases from 8.9
GHz to 10.04 GHz when the concentration of ethanol is changed from 0% to 100%. In
addition, the proposed absorber shows linear frequency shift from 20% to 80% of
the different concentrations of ethanol.
PMID- 27509499
TI - Stochastic Modeling and Analysis of Multiple Nonlinear Accelerated Degradation
Processes through Information Fusion.
AB - Accelerated degradation testing (ADT) is an efficient technique for evaluating
the lifetime of a highly reliable product whose underlying failure process may be
traced by the degradation of the product's performance parameters with time.
However, most research on ADT mainly focuses on a single performance parameter.
In reality, the performance of a modern product is usually characterized by
multiple parameters, and the degradation paths are usually nonlinear. To address
such problems, this paper develops a new s-dependent nonlinear ADT model for
products with multiple performance parameters using a general Wiener process and
copulas. The general Wiener process models the nonlinear ADT data, and the
dependency among different degradation measures is analyzed using the copula
method. An engineering case study on a tuner's ADT data is conducted to
demonstrate the effectiveness of the proposed method. The results illustrate that
the proposed method is quite effective in estimating the lifetime of a product
with s-dependent performance parameters.
PMID- 27509500
TI - Design and Fabrication of Double-Focused Ultrasound Transducers to Achieve Tight
Focusing.
AB - Beauty treatment for skin requires a high-intensity focused ultrasound (HIFU)
transducer to generate coagulative necrosis in a small focal volume (e.g., 1 mm3)
placed at a shallow depth (3-4.5 mm from the skin surface). For this, it is
desirable to make the F-number as small as possible under the largest possible
aperture in order to generate ultrasound energy high enough to induce tissue
coagulation in such a small focal volume. However, satisfying both conditions at
the same time is demanding. To meet the requirements, this paper, therefore,
proposes a double-focusing technique, in which the aperture of an ultrasound
transducer is spherically shaped for initial focusing and an acoustic lens is
used to finally focus ultrasound on a target depth of treatment; it is possible
to achieve the F-number of unity or less while keeping the aperture of a
transducer as large as possible. In accordance with the proposed method, we
designed and fabricated a 7-MHz double-focused ultrasound transducer. The
experimental results demonstrated that the fabricated double-focused transducer
had a focal length of 10.2 mm reduced from an initial focal length of 15.2 mm
and, thus, the F-number changed from 1.52 to 1.02. Based on the results, we
concluded that the proposed double-focusing method is suitable to decrease F
number while maintaining a large aperture size.
PMID- 27509501
TI - Implementation and Analysis of ISM 2.4 GHz Wireless Sensor Network Systems in
Judo Training Venues.
AB - In this work, the performance of ISM 2.4 GHz Wireless Sensor Networks (WSNs)
deployed in judo training venues is analyzed. Judo is a very popular martial art,
which is practiced by thousands of people not only at the competition level, but
also as part of physical education programs at different school levels. There is
a great variety of judo training venues, and each one has specific morphological
aspects, making them unique scenarios in terms of radio propagation due to the
presence of furniture, columns, equipment and the presence of human beings, which
is a major issue as the person density within this kind of scenarios could be
high. Another key aspect is the electromagnetic interference created by other
wireless systems, such as WiFi or other WSNs, which make the radio planning a
complex task in terms of coexistence. In order to analyze the impact of these
features on the radio propagation and the performance of WSNs, an in-house
developed 3D ray launching algorithm has been used. The obtained simulation
results have been validated with a measurement campaign carried out in the sport
facilities of the Public University of Navarre. The analysis is completed with
the inclusion of an application designed to monitor biological constants of
judokas, aimed to improve their training procedures. The application, that allows
the simultaneous monitoring of multiple judokas (collective workouts) minimizing
the efforts of the coach and medical supervisor, is based on commercial off-the
shelf products. The presented assessment of the presence of interfering wireless
systems and the presence of human beings within judo training venues shows that
an in-depth radio planning is required as these issues can have a great impact in
the overall performance of a ISM 2.4 GHz WSN, affecting negatively the potential
applications supported by wireless channel.
PMID- 27509502
TI - Comparative Study of Two Different TiO2 Film Sensors on Response to H2 under UV
Light and Room Temperature.
AB - An anatase TiO2 film sensor was prepared by a facile in-situ method on the
interdigitated Au electrode deposited on the alumina substrate. The structure,
morphology and the optical properties of the in-situ TiO2 film sensor were
characterized by X-ray diffraction, Scanning Electron Microscopy, and UV-vis
diffuse reflectance spectra. The photo-assisted gas sensitivities of the prepared
film towards H2 gas were evaluated at room temperature in N2 and synthetic air
atmospheres. As compared to TiO2 film sensor prepared by drop-coating method,
this in-situ TiO2 film sensor exhibited a more compact structure composed of
uniform TiO2 microspheres as well as a better gas sensitivity towards H2 under UV
irradiation, especially in synthetic air. The photo-electrochemical measurements
suggest that these improvements may be associated with the efficient charge
transfer in the TiO2 interface induced by the TiO2 microsphere structure. This
study might offer a feasible approach to develop photo-assisted gas sensors at
ambient temperature.
PMID- 27509503
TI - Analysis of the Bias on the Beidou GEO Multipath Combinations.
AB - The Beidou navigation satellite system is a very important sensor for positioning
in the Asia-Pacific region. The Beidou inclined geosynchronous orbit (IGSO) and
medium Earth orbit (MEO) satellites have been analysed in some studies previously
conducted by other researchers; this paper seeks to gain more insight regarding
the geostationary earth orbit (GEO) satellites. Employing correlation analysis,
Fourier transformation and wavelet decomposition, we validate whether there is a
systematic bias in their multipath combinations. These biases can be observed
clearly in satellites C01, C02 and C04 and have a great correlation with time
series instead of elevation, being significantly different from those of the
Beidou IGSO and MEO satellites. We propose a correction model to mitigate this
bias based on its daily periodicity characteristic. After the model has been
applied, the performance of the positioning estimations of the eight stations
distributed in the Asia-Pacific region is evaluated and compared. The results
show that residuals of multipath series behaves random noise; for the single
point positioning (SPP) and precise point positioning (PPP) approaches, the
positioning accuracy in the upward direction can be improved by 8 cm and 6 mm,
respectively, and by 2 cm and 4 mm, respectively, for the horizontal component.
PMID- 27509504
TI - Reversed Three-Dimensional Visible Light Indoor Positioning Utilizing Annular
Receivers with Multi-Photodiodes.
AB - Exploiting the increasingly wide use of light emitting diodes (LEDs) lighting, in
this paper we propose a reversed indoor positioning system (IPS) based on LED
visible light communication (VLC) in order to improve indoor positioning
accuracy. Unlike other VLC positioning systems, we employ two annular receivers
with multi-photodiodes installed on the ceiling to locate the persons who carry
LEDs. The basic idea is using multi-photodiodes to calculate the angle while
using the received signal strength (RSS) method to calculate the distance. The
experiment results show that the effective positioning range of the proposed
system is 1.8 m when the distance between two receivers is 1.2 m. Moreover, a
positioning error less than 0.2 m can be achieved under the condition that the
radius of the PIN circle is between 0.16 m and 0.2 m, and the distance of the
transmitter-receiver plane is less than 1.8 m, which will be effective in
practice.
PMID- 27509505
TI - A Novel Cloud-Based Service Robotics Application to Data Center Environmental
Monitoring.
AB - This work presents a robotic application aimed at performing environmental
monitoring in data centers. Due to the high energy density managed in data
centers, environmental monitoring is crucial for controlling air temperature and
humidity throughout the whole environment, in order to improve power efficiency,
avoid hardware failures and maximize the life cycle of IT devices. State of the
art solutions for data center monitoring are nowadays based on environmental
sensor networks, which continuously collect temperature and humidity data. These
solutions are still expensive and do not scale well in large environments. This
paper presents an alternative to environmental sensor networks that relies on
autonomous mobile robots equipped with environmental sensors. The robots are
controlled by a centralized cloud robotics platform that enables autonomous
navigation and provides a remote client user interface for system management.
From the user point of view, our solution simulates an environmental sensor
network. The system can easily be reconfigured in order to adapt to management
requirements and changes in the layout of the data center. For this reason, it is
called the virtual sensor network. This paper discusses the implementation
choices with regards to the particular requirements of the application and
presents and discusses data collected during a long-term experiment in a real
scenario.
PMID- 27509506
TI - Towards a Real-Time Embedded System for Water Monitoring Installed in a Robotic
Sailboat.
AB - Problems related to quality (and quantity) of water in natural resources or in
artificial reservoirs are frequently arising and are at the center of attention
of authorities and governments around the world. Many times the monitoring is not
performed in an efficient time frame and a precise manner, whereas the adoption
of fast and punctual solutions would undoubtedly improve the water quality and
consequently enhance the life of people. To minimize or diminish such kinds of
problems, we propose an architecture for sensors installed in a robotic platform,
an autonomous sail boat, able to acquire raw data relative to water quality, to
process and make them available to people that might be interested in such
information. The main contributions are the sensors architecture itself, which
uses low cost sensors, with practical experimentation done with a prototype.
Results show data collected for points in lakes and rivers in the northeast of
Brazil. This embedded system is fixed in the sailboat robot with the intention to
facilitate the study of water quality for long endurance missions. This robot can
help monitoring water bodies in a more consistent manner. Nonetheless the system
can also be used with fixed vases or buoys in strategic points.
PMID- 27509507
TI - Accurate Behavioral Simulator of All-Digital Time-Domain Smart Temperature
Sensors by Using SIMULINK.
AB - This study proposes a new behavioral simulator that uses SIMULINK for all-digital
CMOS time-domain smart temperature sensors (TDSTSs) for performing rapid and
accurate simulations. Inverter-based TDSTSs offer the benefits of low cost and
simple structure for temperature-to-digital conversion and have been developed.
Typically, electronic design automation tools, such as HSPICE, are used to
simulate TDSTSs for performance evaluations. However, such tools require
extremely long simulation time and complex procedures to analyze the results and
generate figures. In this paper, we organize simple but accurate equations into a
temperature-dependent model (TDM) by which the TDSTSs evaluate temperature
behavior. Furthermore, temperature-sensing models of a single CMOS NOT gate were
devised using HSPICE simulations. Using the TDM and these temperature-sensing
models, a novel simulator in SIMULINK environment was developed to substantially
accelerate the simulation and simplify the evaluation procedures. Experiments
demonstrated that the simulation results of the proposed simulator have favorable
agreement with those obtained from HSPICE simulations, showing that the proposed
simulator functions successfully. This is the first behavioral simulator
addressing the rapid simulation of TDSTSs.
PMID- 27509508
TI - A Study of a Handrim-Activated Power-Assist Wheelchair Based on a Non-Contact
Torque Sensor.
AB - Demand for wheelchairs is increasing with growing numbers of aged and disabled
persons. Manual wheelchairs are the most commonly used assistive device for
mobility because they are convenient to transport. Manual wheelchairs have
several advantages but are not easy to use for the elderly or those who lack
muscular strength. Therefore, handrim-activated power-assist wheelchairs (HAPAW)
that can aid driving power with a motor by detecting user driving intentions
through the handrim are being researched. This research will be on HAPAW that
judge user driving intentions by using non-contact torque sensors. To deliver the
desired motion, which is sensed from handrim rotation relative to a fixed
controller, a new driving wheel mechanism is designed by applying a non-contact
torque sensor, and corresponding torques are simulated. Torques are measured by a
driving wheel prototype and compared with simulation results. The HAPAW prototype
was developed using the wheels and a driving control algorithm that uses left and
right input torques and time differences are used to check if the non-contact
torque sensor can distinguish users' driving intentions. Through this procedure,
it was confirmed that the proposed sensor can be used effectively in HAPAW.
PMID- 27509509
TI - Probing the Kinetic Anabolism of Poly-Beta-Hydroxybutyrate in Cupriavidus necator
H16 Using Single-Cell Raman Spectroscopy.
AB - Poly-beta-hydroxybutyrate (PHB) can be formed in large amounts in Cupriavidus
necator and is important for the industrial production of biodegradable plastics.
In this investigation, laser tweezers Raman spectroscopy (LTRS) was used to
characterize dynamic changes in PHB content-as well as in the contents of other
common biomolecule-in C. necator during batch growth at both the population and
single-cell levels. PHB accumulation began in the early stages of bacterial
growth, and the maximum PHB production rate occurred in the early and middle
exponential phases. The active biosynthesis of DNA, RNA, and proteins occurred in
the lag and early exponential phases, whereas the levels of these molecules
decreased continuously during the remaining fermentation process until the
minimum values were reached. The PHB content inside single cells was relatively
homogenous in the middle stage of fermentation; during the late growth stage, the
variation in PHB levels between cells increased. In addition, bacterial cells in
various growth phases could be clearly discriminated when principle component
analysis was performed on the spectral data. These results suggest that LTRS is a
valuable single-cell analysis tool that can provide more comprehensive
information about the physiological state of a growing microbial population.
PMID- 27509510
TI - Thermal Image Sensing Model for Robotic Planning and Search.
AB - This work presents a search planning system for a rolling robot to find a source
of infra-red (IR) radiation at an unknown location. Heat emissions are observed
by a low-cost home-made IR passive visual sensor. The sensor capability for
detection of radiation spectra was experimentally characterized. The sensor data
were modeled by an exponential model to estimate the distance as a function of
the IR image's intensity, and, a polynomial model to estimate temperature as a
function of IR intensities. Both theoretical models are combined to deduce a
subtle nonlinear exact solution via distance-temperature. A planning system
obtains feed back from the IR camera (position, intensity, and temperature) to
lead the robot to find the heat source. The planner is a system of nonlinear
equations recursively solved by a Newton-based approach to estimate the IR-source
in global coordinates. The planning system assists an autonomous navigation
control in order to reach the goal and avoid collisions. Trigonometric partial
differential equations were established to control the robot's course towards the
heat emission. A sine function produces attractive accelerations toward the IR
source. A cosine function produces repulsive accelerations against the obstacles
observed by an RGB-D sensor. Simulations and real experiments of complex indoor
are presented to illustrate the convenience and efficacy of the proposed
approach.
PMID- 27509511
TI - Shift in HIV/AIDS Epidemic in Southeastern China: A Longitudinal Study from 1987
to 2015.
AB - OBJECTIVE: The aim of this study was to investigate the shift in the
epidemiological features of HIV/AIDS during the last three decades in Fujian
Province, southeastern China, so as to provide evidence for the development of
novel HIV/AIDS control strategies. METHODS: Data pertaining to the conventional
surveillance, sentinel surveillance and epidemiological survey in Fujian Province
during the period from 1987 to 2015 were collected. The epidemiological trends
were described, and the subtypes of HIV strain were genotyped. In addition, the
response to antiretroviral therapy was evaluated, and HIV genotypic resistance
was assayed. RESULTS: There was an increasing trend observed in the reported
cases of HIV/AIDS in Fujian Province. From 1987 to the end of 2015, a total of
8651 HIV/AIDS cases were reported across the province, with totally 1557 deaths
found. Among the total cases, the ratio of male/female cases was 3.7:1, which
appeared to be an increasing trend; 77.1% cases were detected in young and middle
aged populations aged 19 to 50 years, however, the new HIV infections recently
tended to occur in young people aged 15 to 18 years and in populations aged 50
years and older. Among all infected individuals, 49.3% were married, however, the
percentage of unmarried cases increased from 6.67% before 1994 to 40.1% in 2015;
64.8% had junior high school education or lower, however, the proportion of
HIV/AIDS cases with junior college education or above gradually increased from
6.5% in 2009 to 21.4% in 2015. The reported HIV/AIDS cases were predominantly
found in coastal regions; however, a rapidly increasing trend was seen in the
number of HIV/AIDS cases in inland regions, and the geographical variation of the
cases gradually reduced. There were multiple routes of HIV transmission found in
Fujian Province, and 94.2% infections were sexually transmitted, with a large
increase in the percentage of male homosexual transmission. A variety of HIV-1
subtypes were genotyped in the province during the study period, and CRF01-AE and
CRF07-BC intersubtype recombinant forms were predominant; however, a declining
trend in the proportion of HIV-1 CRF01-AE recombinant virus and a significant
rise in the proportion of HIV-1 CRF07-BC recombinant virus were observed. Over
90% HIV inhibition was found in all cases receiving antiretroviral therapy during
the period from 2011 to 2015, indicating a low prevalence of HIV drug resistance.
CONCLUSIONS: An increasing trend is still observed in the HIV/AIDS epidemics in
Fujian Province, southeastern China. However, the epidemiological pattern of
HIV/AIDS has recently changed in the province, and effective control
interventions targeting the shift in the epidemiological features of HIV/AIDS
should therefore be implemented to control the spread of the epidemic.
PMID- 27509512
TI - The Covariance between Air Pollution Annoyance and Noise Annoyance, and Its
Relationship with Health-Related Quality of Life.
AB - Air pollution originating from road traffic is a known risk factor of respiratory
and cardiovascular disease (both in terms of chronic and acute effects). While
adverse effects on cardiovascular health have also been linked with noise (after
controlling for air pollution), noise exposure has been commonly linked to sleep
impairment and negative emotional reactions. Health is multi-faceted, both
conceptually and operationally; Health-Related Quality of Life (HRQOL) is one of
many measures capable of probing health. In this study, we examine pre-collected
data from postal surveys probing HRQOL obtained from a variety of urban,
suburban, and rural contexts across the North Island of New Zealand. Analyses
focus on the covariance between air pollution annoyance and noise annoyances, and
their independent and combined effects on HRQOL. Results indicate that the
highest ratings of air pollution annoyance and noise annoyances were for
residents living close to the motorway, while the lowest were for rural
residents. Most of the city samples indicated no significant difference between
air pollution- and noise-annoyance ratings, and of all of the correlations
between air pollution- and noise-annoyance, the highest were found in the city
samples. These findings suggest that annoyance is driven by exposure to
environmental factors and not personality characteristics. Analysis of HRQOL
indicated that air pollution annoyance predicts greater variability in the
physical HRQOL domain while noise annoyance predicts greater variability in the
psychological, social and environmental domains. The lack of an interaction
effect between air pollution annoyance and noise annoyance suggests that air
pollution and noise impact on health independently. These results echo those
obtained from objective measures of health and suggest that mitigation of traffic
effects should address both air and noise pollution.
PMID- 27509513
TI - Increasing HIV Incidence among Men Who Have Sex with Men in Jiangsu Province,
China: Results from Five Consecutive Surveys, 2011-2015.
AB - Epidemics of HIV among men who have sex with men (MSM) are major public health
concerns in most parts of China. This study examined the trends in HIV incidence
and associated factors among MSM in Jiangsu Province. Five consecutive cross
sectional surveys were conducted among MSM from 2011 to 2015 in eight cities
throughout Jiangsu Province. Participants were recruited from MSM venues or via
the internet. Demographic and behavioral data were collected through HIV bio
behavioral surveys. Blood specimens were collected to test for HIV and syphilis.
HIV incidence was estimated by the IgG-capture BED-EIA (BED) method and a chi
square trend test was used to compare differences over the years. Multivariate
logistic regression analysis was used to identify factors associated with recent
infection. A total of 2433, 2678, 2591, 2610 and 2541 participants were enrolled
in 2011, 2012, 2013, 2014 and 2015, respectively. HIV incidence increased from
5.10% in 2011 to 6.62% in 2015 (p = 0.025). MSM who had an education level of
junior high school or less (aOR = 1.472, p = 0.018), engaged in condomless anal
sex in the past 6 months (aOR = 2.389, p < 0.001), did not have an HIV test in
the past 12 months (aOR = 3.215, p < 0.001), and were currently infected with
syphilis (aOR = 2.025, p = 0.001) were likely to be recently infected with HIV.
HIV incidence is increasing among MSM in Jiangsu Province, China. Condom usage
and HIV testing promotion should be prioritized when attempting to reduce HIV
transmission among MSM in China.
PMID- 27509514
TI - Quality of Life and Its Related Factors in Chinese Unemployed People: A
Population-Based Cross-Sectional Study.
AB - With the global economic crisis and industrial restructuring, the unemployed are
suffering from job loss-related stress and loss of income, which is believed to
impair their mental and physical health, while coping and self-efficacy could
combat the adverse effects of unemployment on health. Thus, this study aims to
describe quality of life (QOL) among unemployed Chinese people and explore the
associated factors. A cross-sectional study was conducted by convenience
sampling, composed of 1825 unemployed people, from January 2011 to September
2011. Questionnaires pertaining to demographic characteristics, the 36-item Short
Form Health Survey (SF-36), the abbreviated version of the Cope Inventory (Brief
COPE) and self-efficacy scales were used to collect information from unemployed
people in the eastern, central, and western regions of China. Hierarchical
multiple regression analysis was performed to explore the related factors of QOL.
A structural equation model (SEM) was used to test the relations among coping,
self-efficacy, and QOL. Mental QOL was significantly lower than physical QOL in
Chinese unemployed people. Coping had significant effects on both physical
component summary (PCS) and mental component summary (MCS), while self-efficacy
played the mediating role in the association between Coping and QOL. Unemployed
Chinese people's mental QOL was disrupted more seriously than their physical QOL.
An increase in coping could improve QOL by promoting better management of issues
brought about by unemployment. In addition, self-efficacy has the ability to
reduce the impact of unemployment on QOL, through the mediating path of coping on
QOL. This study highlights the need of coping skills training and self-efficacy
enhancement for better management of unemployment in order to improve QOL and
well-being.
PMID- 27509515
TI - The Regularities in Insufficient Leisure-Time Physical Activity in Poland.
AB - BACKGROUND: Insufficient physical activity (PA) has become an increasing risk
factor of noncommunicable diseases and an important cause of deaths all over the
world. The goal of this paper is to provide an in-depth description of
insufficient PA in Poland as well as an examination of some of its correlates.
METHODS: We take advantage of statistical and econometric (logistic regression)
analysis on the basis of a representative survey. Out of 3056 respondents, we
analyze the 1260 low-PA ones. RESULTS: The household size is more significant
than the household life phase, and only several professions increase the odds of
insufficient PA. The influence of socioeconomic status and place of residence is
most robust. Gender does not significantly influence insufficient PA. Physical
inactivity is concentrated among inhabitants of rural areas and town dwellers,
with poor educational profile, and limited labor market opportunities. However,
even high socioeconomic status does not completely prevent insufficient activity.
CONCLUSIONS: Groups at the highest risk of inactivity should be covered by
promotional actions first. Their aim should mainly be raising the leisure-time
physical activity (LTPA) awareness. To start with, primary forms of activity
would be walking, Nordic walking and jogging.
PMID- 27509516
TI - Effects of Long-Term Exposure to 60 GHz Millimeter-Wavelength Radiation on the
Genotoxicity and Heat Shock Protein (Hsp) Expression of Cells Derived from Human
Eye.
AB - Human corneal epithelial (HCE-T) and human lens epithelial (SRA01/04) cells
derived from the human eye were exposed to 60 gigahertz (GHz) millimeter
wavelength radiation for 24 h. There was no statistically significant increase in
the micronucleus (MN) frequency in cells exposed to 60 GHz millimeter-wavelength
radiation at 1 mW/cm2 compared with sham-exposed controls and incubator controls.
The MN frequency of cells treated with bleomycin for 1 h provided positive
controls. The comet assay, used to detect DNA strand breaks, and heat shock
protein (Hsp) expression also showed no statistically significant effects of
exposure. These results indicate that exposure to millimeter-wavelength radiation
has no effect on genotoxicity in human eye cells.
PMID- 27509517
TI - Particulate Matter in Second-Hand Smoke Emitted from Different Cigarette Sizes
and Types of the Brand Vogue Mainly Smoked by Women.
AB - Indoor air pollution with harmful particulate matter (PM) is mainly caused by
cigarette smoke. Super-Slim-Size-Cigarettes (SSL) are considered a less harmful
alternative to King-Size-Cigarettes (KSC) due to longer filters and relatively
low contents. We ask if "Combined Mainstream and Sidestream Smoke" (CMSS)
associated PM levels of SSL are lower than of KSC and thus are potentially less
harmful. PM concentrations in CMSS (PM10, PM2.5, and PM1) are measured from four
cigarette types of the brand Vogue, using an "automatic-environmental-tobacco
smoke-emitter" (AETSE) and laser aerosol spectrometry: SSL-BLEUE, -MENTHE, -LILAS
and KSC-La Cigarette and -3R4F reference. This analysis shows that SSL MENTHE
emitted the highest amount of PM, and KSC-La Cigarette the lowest. 3R4F reference
emitted PM in the middle range, exceeding SSL BLEUE and falling slightly below
SSL LILAS. It emerged that PM1 constituted the biggest proportion of PM emission.
The outcome shows significant type-specific differences for emitted PM
concentrations. Our results indicate that SSL are potentially more harmful for
passive smokers than the respective KSC. However, this study cannot give precise
statements about the general influence of the size of a cigarette on PM. Alarming
is that PM1 is responsible for the biggest proportion of PM pollution, since
smaller particles cause more harmful effects.
PMID- 27509518
TI - Hepatitis E Seroprevalence in Europe: A Meta-Analysis.
AB - There have been large numbers of studies on anti-HEV IgG seroprevalence in
Europe, however, the results of these studies have produced high variability of
seroprevalence rates, making interpretation increasingly problematic. Therefore,
the aim of this study was to develop a clearer understanding of anti-HEV IgG
seroprevalence in Europe and identify risk groups for HEV exposure by a meta
analysis of published studies. METHODS: All European HEV-seroprevalence studies
from 2003 to 2015 were reviewed. Data were stratified by assay, geographical
location, and patient cohort (general population, patients with HIV, solid-organ
transplant recipients, chronic liver disease patients, and individuals in contact
with swine/wild animals). Data were pooled using a mixed-effects model. RESULTS:
Four hundred thirty-two studies were initially identified, of which 73 studies
were included in the analysis. Seroprevalence estimates ranged from 0.6% to
52.5%, increased with age, but were unrelated to gender. General population
seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%,
MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported
significantly higher seroprevalence rates across all cohorts (p < 0.001).
Individuals in contact with swine/wild animals had significantly higher
seroprevalence rates than the general population, irrespective of assay (p <
0.0001). There was no difference between any other cohorts. The highest
seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT:
7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed
heterogeneity was attributed to geographical region (23%), assay employed (23%)
and study cohort (7%). CONCLUSION: Seroprevalcence rates primarily depend on the
seroassy that is used, followed by the geographical region and study cohort.
Seroprevalence is higher in individuals exposed to swine and/or wild animals, and
increases with age.
PMID- 27509519
TI - Compliance, Palatability and Feasibility of PALEOLITHIC and Australian Guide to
Healthy Eating Diets in Healthy Women: A 4-Week Dietary Intervention.
AB - (1) BACKGROUND/OBJECTIVES: The Paleolithic diet has been receiving media coverage
in Australia and claims to improve overall health. The diet removes grains and
dairy, whilst encouraging consumption of fruits, vegetables, meat, eggs and nuts.
Our aim was to compare the diet to the Australian Guide to Healthy Eating (AGHE)
in terms of compliance, palatability and feasibility; (2) SUBJECTS/METHODS: 39
healthy women (age 47 +/- 13 years, BMI 27 +/- 4 kg/m2) were randomised to an ad
libitum Paleolithic (n = 22) or AGHE diet (n = 17) for 4-weeks. A food checklist
was completed daily, with mean discretionary consumption (serves/day) calculated
to assess compliance. A 12-item questionnaire was administered post intervention
to assess palatability and feasibility; (3) RESULTS: The AGHE group reported
greater daily consumption of discretionary items (1.0 + 0.6 vs. 0.57 + 0.6
serves/day, p = 0.03). Compared to the AGHE group, the Paleolithic group reported
a significantly greater number of events of diarrhoea (23%, 0%, p = 0.046), costs
associated with grocery shopping (69%, 6% p < 0.01) and belief that the diet was
not healthy (43%, 0% p < 0.01); (4) CONCLUSIONS: Compliance to both diets was
high but the potential side effects and increased cost suggest that the
Paleolithic diet may not be practical in clinical/public health settings. Further
studies are required to assess longer term feasibility.
PMID- 27509520
TI - The Effect of the Sodium to Potassium Ratio on Hypertension Prevalence: A
Propensity Score Matching Approach.
AB - This study investigated the effect of the sodium to potassium ratio on
hypertension prevalence and blood pressure. The study population was constructed
by pooling the Korean National Health and Nutrition Examination Surveys between
2010 and 2014. The study population was divided into quartiles based on the
sodium to potassium ratio, and the effect was inferred by the difference in
hypertension prevalence across quartiles by six pairwise comparisons using a
propensity score matching technique. The quartiles with the higher sodium to
potassium ratio had higher hypertension prevalence rates based on the following
pairwise comparisons: the first vs. third quartile, the first vs. fourth
quartile, the second vs. third quartile, and the second vs. fourth quartile. The
prevalence differences were 2.74% point (p < 0.05), 3.44% point (p < 0.01), 2.47%
point (p < 0.05), and 2.95% point (p < 0.01), respectively. In addition,
statistically significant higher systolic (p < 0.05) and diastolic blood pressure
(p < 0.01) was observed in the second quartiles compared to the first quartiles.
Because a strong association was also detected between the sodium to potassium
ratio and blood pressure even at a low level of sodium to potassium ratio, a
lower sodium to potassium ratio diet than a usual diet is recommended to control
high blood pressure in Korea.
PMID- 27509521
TI - Effect of Probiotics on Depression: A Systematic Review and Meta-Analysis of
Randomized Controlled Trials.
AB - It has been reported that gut probiotics play a major role in the bidirectional
communication between the gut and the brain. Probiotics may be essential to
people with depression, which remains a global health challenge, as depression is
a metabolic brain disorder. However, the efficacy of probiotics for depression is
controversial. This study aimed to systematically review the existing evidence on
the effect of probiotics-based interventions on depression. Randomized,
controlled trials, identified through screening multiple databases and grey
literature, were included in the meta-analysis. The meta-analysis was performed
using Review Manager 5.3 software using a fixed-effects model. The meta-analysis
showed that probiotics significantly decreased the depression scale score (MD
(depressive disorder) = -0.30, 95% CI (-0.51--0.09), p = 0.005) in the subjects.
Probiotics had an effect on both the healthy population (MD = -0.25, 95% CI (
0.47--0.03), p = 0.03) and patients with major depressive disorder (MDD) (MD =
0.73, 95% CI (-1.37--0.09), p = 0.03). Probiotics had an effect on the population
aged under 60 (MD = -0.43, 95% CI (-0.72--0.13), p = 0.005), while it had no
effect on people aged over 65 (MD = -0.18, 95% CI (-0.47-0.11), p = 0.22). This
is the first systematic review and meta-analysis with the goal of determining the
effect of probiotics on depression. We found that probiotics were associated with
a significant reduction in depression, underscoring the need for additional
research on this potential preventive strategy for depression.
PMID- 27509522
TI - Maternal Methyl-Group Donor Intake and Global DNA (Hydroxy)Methylation before and
during Pregnancy.
AB - It is still unclear to which extent methyl-group intake during pregnancy can
affect maternal global DNA (hydroxyl)methylation. Pregnancy methylation profiling
and its link with methyl-group intake in a healthy population could enhance our
understanding of the development of pregnancy related disorders. One hundred
forty-eight women were enrolled in the MANOE (MAternal Nutrition and Offspring's
Epigenome) study. Thiry-four women were enrolled before pregnancy and 116 during
the first trimester of pregnancy. Global DNA (hydroxy)methylation in blood using
LC-MS/MS and dietary methyl-group intake (methionine, folate, betaine, and
choline) using a food-frequency questionnaire were estimated pre-pregnancy,
during each trimester, and at delivery. Global DNA (hydroxy)methylation levels
were highest pre-pregnancy and at weeks 18-22 of pregnancy. We observed a
positive relation between folic acid and global DNA methylation (p = 0.04) and
hydroxymethylation (p = 0.04). A high intake of methionine pre-pregnancy and in
the first trimester showed lower (hydroxy)methylation percentage in weeks 11-13
and weeks 18-22, respectively. Choline and betaine intake in the first weeks was
negatively associated with hydroxymethylation. Women with a high intake of these
three methyl groups in the second and third trimester showed higher
hyrdoxymethylation/methylation levels in the third trimester. To conclude, a time
trend in DNA (hydroxy)methylation was found and women with higher methyl-group
intake showed higher methylation in the third trimester, and not in earlier
phases of pregnancy.
PMID- 27509523
TI - Sex-Specific Sociodemographic Correlates of Dietary Patterns in a Large Sample of
French Elderly Individuals.
AB - This cross-sectional analysis provides up-to-date information about dietary
patterns (DP) and their sociodemographic correlates in European elderly
individuals. We studied 6686 enrollees aged 65+ (55% women) in the ongoing French
population-based NutriNet-Sante e-cohort. Diet was assessed via three 24 h
records. The sex-specific correlates of factor analysis derived DP were
identified with multivariable linear regression. Using 22 pre-defined food
groups, three DP were extracted. The "healthy" DP (fruit, vegetables, grains,
nuts, fish) was positively associated with education, living alone, and being a
former smoker (women), and negatively associated with being overweight, current
smoker (men), age 75+ years, having hypertension, and obesity (women). The
"western" DP (meat, appetizers, cheese, alcohol) was positively associated with
BMI (men) and being a former/current smoker; it was negatively associated with
age 75+ years (women) and living alone. The "traditional" DP (bread, potatoes,
milk, vegetables, butter, stock) was positively associated with age and
negatively associated with being a former/current smoker, education (men), and
residing in an urban/semi-urban area. The findings support the diversity of DP
among the elderly, highlighting sex-specific differences. The "healthy" DP
explained the largest amount of variance in intake. Future studies could
replicate the models in longitudinal and international contexts.
PMID- 27509524
TI - A Rapid Assay to Detect Toxigenic Penicillium spp. Contamination in Wine and
Musts.
AB - Wine and fermenting musts are grape products widely consumed worldwide. Since the
presence of mycotoxin-producing fungi may greatly compromise their quality
characteristics and safety, there is an increasing need for relatively rapid
"user friendly" quantitative assays to detect fungal contamination both in grapes
delivered to wineries and in final products. Although other fungi are most
frequently involved in grape deterioration, secondary infections by Penicillium
spp. are quite common, especially in cool areas with high humidity and in wines
obtained by partially dried grapes. In this work, a single-tube nested real-time
PCR approach-successfully applied to hazelnut and peanut allergen detection-was
tested for the first time to trace Penicillium spp. in musts and wines. The
method consisted of two sets of primers specifically designed to target the beta
tubulin gene, to be simultaneously applied with the aim of lowering the detection
limit of conventional real-time PCR. The assay was able to detect up to 1 fg of
Penicillium DNA. As confirmation, patulin content of representative samples was
determined. Most of analyzed wines/musts returned contaminated results at >50 ppb
and a 76% accordance with molecular assay was observed. Although further large
scale trials are needed, these results encourage the use of the newly developed
method in the pre-screening of fresh and processed grapes for the presence of
Penicillium DNA before the evaluation of related toxins.
PMID- 27509525
TI - Ultra Large Gene Families: A Matter of Adaptation or Genomic Parasites?
AB - Gene duplication is an important mechanism of molecular evolution. It offers a
fast track to modification, diversification, redundancy or rescue of gene
function. However, duplication may also be neutral or (slightly) deleterious, and
often ends in pseudo-geneisation. Here, we investigate the phylogenetic
distribution of ultra large gene families on long and short evolutionary time
scales. In particular, we focus on a family of NACHT-domain and leucine-rich
repeat-containing (NLR)-genes, which we previously found in large numbers to
occupy one chromosome arm of the zebrafish genome. We were interested to see
whether such a tight clustering is characteristic for ultra large gene families.
Our data reconfirm that most gene family inflations are lineage-specific, but we
can only identify very few gene clusters. Based on our observations we
hypothesise that, beyond a certain size threshold, ultra large gene families
continue to proliferate in a mechanism we term "run-away evolution". This process
might ultimately lead to the failure of genomic integrity and drive species to
extinction.
PMID- 27509526
TI - Clearance of Streptococcus suis in Stomach Contents of Differently Fed Growing
Pigs.
AB - Streptococcus (S.) suis translocates across the intestinal barrier of piglets
after intraintestinal application. Based on these findings, an oro
gastrointestinal infection route has been proposed. Thus, the objective of this
study was to investigate the survival of S. suis in the porcine stomach. Whereas
surviving bacteria of S. suis serotypes 2 and 9 were not detectable after 60 min
of incubation in stomach contents with a comparatively high gastric pH of 5 due
to feeding of fine pellets, the number of Salmonella Derby bacteria increased
under these conditions. Further experiments confirmed the clearance of S. suis
serotypes 2 and 9 within 30 min in stomach contents with a pH of 4.7
independently of the bacterial growth phase. Finally, an oral infection
experiment was conducted, feeding each of 18 piglets a diet mixed with 10(10) CFU
of S. suis serotype 2 or 9. Thorough bacteriological screenings of various
mesenteric-intestinal lymph nodes and internal organs after different times of
exposure did not lead to any detection of the orally applied challenge strains.
In conclusion, the porcine stomach constitutes a very efficient barrier against
oro-gastrointenstinal S. suis infections. Conditions leading to the passage of S.
suis through the stomach remain to be identified.
PMID- 27509528
TI - Permeability-Selectivity Analysis of Microfiltration and Ultrafiltration
Membranes: Effect of Pore Size and Shape Distribution and Membrane Stretching.
AB - We present a modeling approach to determine the permeability-selectivity tradeoff
for microfiltration and ultrafiltration membranes with a distribution of pore
sizes and pore shapes. Using the formulated permeability-selectivity model, the
effect of pore aspect ratio and pore size distribution on the permeability
selectivity tradeoff of the membrane is analyzed. A finite element model is
developed to study the effect of membrane stretching on the distribution of pore
sizes and shapes in the stretched membrane. The effect of membrane stretching on
the permeability-selectivity tradeoff of membranes is also analyzed. The results
show that increasing pore aspect ratio improves membrane performance while
increasing the width of pore size distribution deteriorates the performance. It
was also found that the effect of membrane stretching on the permeability
selectivity tradeoff is greatly affected by the uniformity of pore distribution
in the membrane. Stretching showed a positive shift in the permeability
selectivity tradeoff curve of membranes with well-dispersed pores while in the
case of pore clustering, a negative shift in the permeability-selectivity
tradeoff curve was observed.
PMID- 27509527
TI - Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and
Therapeutic Targeting.
AB - Recent years have seen significant efforts in understanding and modulating the
immune response in cancer. In this context, immunosuppressive cells, including
regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), have
come under intense investigation for their proposed roles in suppressing tumor
specific immune responses and establishing an immunosuppressive tumor
microenvironment, thus enabling tumor immune evasion. Additionally, recent
evidence indicates that Tregs comprise diverse and heterogeneous subsets;
phenotypically and functionally distinct subsets of tumor-infiltrating Tregs
could contribute differently to cancer prognosis and clinical outcomes.
Understanding Treg biology in the setting of cancer, and specifically the tumor
microenvironment, is important for designing effective cancer therapies. In this
review, we critically examine the role of Tregs in the tumor microenvironment and
in cancer progression focusing on human studies. We also discuss the impact of
current therapeutic modalities on Treg biology and the therapeutic opportunities
for targeting Tregs to enhance anti-tumor immune responses and clinical benefits.
PMID- 27509529
TI - Nanopore-CMOS Interfaces for DNA Sequencing.
AB - DNA sequencers based on nanopore sensors present an opportunity for a significant
break from the template-based incumbents of the last forty years. Key advantages
ushered by nanopore technology include a simplified chemistry and the ability to
interface to CMOS technology. The latter opportunity offers substantial promise
for improvement in sequencing speed, size and cost. This paper reviews existing
and emerging means of interfacing nanopores to CMOS technology with an emphasis
on massively-arrayed structures. It presents this in the context of incumbent DNA
sequencing techniques, reviews and quantifies nanopore characteristics and models
and presents CMOS circuit methods for the amplification of low-current nanopore
signals in such interfaces.
PMID- 27509530
TI - Effects of Surface Epitope Coverage on the Sensitivity of Displacement Assays
that Employ Modified Nanoparticles: Using Bisphenol A as a Model Analyte.
AB - With the ever-increasing use of nanoparticles in immunosensors, a fundamental
study on the effect of epitope density is presented herein, with a small molecule
epitope, on the performance of the displacement assay format in an enzyme-linked
immunosorbent assay (ELISA). Thiolated bisphenol A (BPA) functionalized gold
nanoparticles (cysBPAv-AuNPs) and specific anti-BPA antibodies are employed for
this purpose. It is shown that the displacement of cysBPAv-AuNPs bound to the
immobilized antibodies was influenced by both the avidity of bound cysBPAv-AuNPs
and the concentration of free BPA to displace it. The importance of surface
epitope density was that it changed the number of epitopes in close proximity to
the antibody-binding site. This then influenced the avidity of cysBPAv-AuNPs
bound to the immobilized antibody. Furthermore, the molar epitope concentration
in an assay appears to affect the degree of antibody binding site saturation.
Controlling surface epitope density of the functionalized nanoparticles and molar
epitope concentration in an assay leads to a decrease of the concentration of
free BPA required to displace the bound cysBPAv-AuNP, and hence better assay
performance with regards to the D50 value and dynamic range in the displacement
assay.
PMID- 27509531
TI - DJ-1/Park7 Sensitive Na+ /H+ Exchanger 1 (NHE1) in CD4+ T Cells.
AB - DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and
presumably contributing to the control of oxidative stress responses and thus
inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's
disease presumably by augmenting oxidative stress. Formation of reactive oxygen
species (ROS) is paralleled by activation of the Na+ /H+ exchanger 1 (NHE1). ROS
formation in CD4+ T cells plays a decisive role in regulating inflammatory
responses. In the present study, we explored whether DJ-1 is expressed in CD4+ T
cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ
1 and NHE1 transcript, and protein levels were quantified by qRT-PCR and Western
blotting, respectively, intracellular pH (pHi ) utilizing bis-(2-carboxyethyl)-5
(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from
realkalinization after an ammonium pulse, and ROS production utilizing 2',7'
dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed
in CD4+ T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE
activity were higher in CD4+ T cells from DJ-1 deficient mice than in CD4+ T
cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein
tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1
deficient CD4+ T cells, and blunted the difference between DJ-1-/- and DJ-1+/+
CD4+ T cells, an observation pointing to a role of ROS in the up-regulation of
NHE1 in DJ-1-/- CD4+ T cells. In conclusion, DJ-1 is a powerful regulator of ROS
production as well as NHE1 expression and activity in CD4+ T cells. J. Cell.
Physiol. 232: 3050-3059, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27509532
TI - Elevated 1-h post-challenge glucose levels associated with increased arterial
stiffness.
PMID- 27509534
TI - Graft-to-recipient weight ratio threshold adjusted to the model for end-stage
liver disease score for living donor liver transplantation.
AB - The graft-to-recipient weight ratio (GRWR) is an important selection criterion
for living donor liver transplantation (LDLT). The generally accepted threshold
is known to be 0.8%. We believe that this threshold can be reduced under certain
conditions. The aim of this study was to evaluate the results of these patients
with GRWR < 0.8%. Between 2004 and 2015, 649 patients underwent right lobe LDLT
for end-stage liver disease in adult patients. All recipients who had GRWR < 0.8%
were identified. The data of these patients were retrospectively analyzed and
compared to patients with GRWR >= 0.8%. There were 43 patients with GRWR < 0.8%.
Out of these patients, 7 (16%) had GRWR of 0.6%. The median Model for End-Stage
Liver Disease (MELD) score was 15, and the median donor age was 30 years.
Anterior segment drainage was ensured. Portal inflow modulation was performed by
splenic artery ligation according to the portal flow. Postoperative complications
were seen in 6 (14%) patients. Of all 43 patients, 3 (7%) died perioperatively
within 1 month, and 1 (2%) patient underwent retransplantation due to graft
failure. The mean hospital stay was 18 days. The 1-year survival rate was 93%.
None of the patients had a laboratory MELD score above 20. The comparison of the
results with the patients who had GRWR >= 0.8% has shown no significant
difference, except MELD score, body mass index (BMI), and rate of anterior
segment drainage. The GRWR can be decreased even to 0.6% if the MELD score is
below 20, donor age is below 45 years, and there are no signs for any
hepatosteatosis of the donor graft. In these patients, it is essential that the
anterior segment drainage is secured and the portal inflow modulation is
performed according to the portal flow. Liver Transplantation 22 1643-1648 2016
AASLD.
PMID- 27509535
TI - Laparoscopic Common Bile Duct Exploration Versus Open Approach in Cirrhotic
Patients with Choledocholithiasis: A Retrospective Study.
AB - OBJECTIVE: To evaluate the safety and benefits of laparoscopic common bile duct
exploration (LCBDE) compared with open approach (OCBDE) in cirrhotic patients.
MATERIALS AND METHODS: Between January 2009 and December 2012, a total of 113
cirrhotic patients with choledocholithiasis underwent common bile duct (CBD)
explorations in our department. There were two groups of patients: A:LCBDE (n =
61) and B:OCBDE (n = 52). Patients' demographic characteristics, surgical data,
postoperative outcomes, and long-term results were retrospectively collected and
analyzed. RESULTS: There were no significant differences between the two groups
in the demographic characteristics or preoperative status. The transcystic
approach was successfully performed in 52 (46.0%) patients (group A:34, group
B:20), whereas choledochotomy was successful in 59 (54.0%) patients (group A:27,
group B:32). The differences between group A and group B in terms of surgical
time (124.9 +/- 34.2 minutes versus 132.6 +/- 48.6 minutes, P = .323), stone
clearance rate (93.4% versus 94.2%, P > .05), short-term complication rate (9.8%
versus 13.4%, P = .547), and recurrent stone rate (6.6% versus 5.8%, P > .05)
were not statistically significant. However, group A suffered less blood loss [95
(60-200) mL versus 200 (90-450) mL, P < .001] and shorter length of hospital stay
(4.7 +/- 2.5 days versus 11.3 +/- 3.1 days, P < .001) than group B. In the LCBDE
group, 4 (6.6%) patients were converted due to heavy inflammation and severe
adhesions. No mortality, biliary injury, or stricture occurred during follow-up.
CONCLUSION: LCBDE can be safely performed in patients with Child-Pugh A or B
cirrhosis and choledocholithiasis, with considerable efficiency, minimal short
term complications, and acceptable long-term outcomes. LCBDE has the advantages
over open CBD exploration of less bleeding and reduced length of hospital stay.
PMID- 27509536
TI - Fate of Polycyclic Aromatic Hydrocarbons in Seawater from the Western Pacific to
the Southern Ocean (17.5 degrees N to 69.2 degrees S) and Their Inventories on
the Antarctic Shelf.
AB - Semivolatile organic compounds such as polycyclic aromatic hydrocarbons (PAHs)
have the potential to reach pristine environments through long-range transport.
To investigate the long-range transport of the PAHs and their fate in Antarctic
seawater, dissolved PAHs in the surface waters from the western Pacific to the
Southern Ocean (17.5 degrees N to 69.2 degrees S), as well as down to 3500 m PAH
profiles in Prydz Bay and the adjacent Southern Ocean, were observed during the
27th Chinese National Antarctic Research Expedition in 2010. The concentrations
of Sigma9PAH in the surface seawater ranged from not detected (ND) to 21 ng L(
1), with a mean of 4.3 ng L(-1); and three-ring PAHs were the most abundant
compounds. Samples close to the Australian mainland displayed the highest levels
across the cruise. PAHs originated mainly from pyrogenic sources, such as grass,
wood, and coal combustion. Vertical profiles of PAHs in Prydz Bay showed a
maximum at a depth of 50 m and less variance with depth. In general, we inferred
that the water masses as well as the phytoplankton were possible influencing
factors on PAH surface-enrichment depth-depletion distribution. Inventory
estimation highlighted the contribution of intermediate and deep seawater on
storing PAHs in seawater from Prydz Bay, and suggested that climate change rarely
shows the rapid release of the PAHs currently stored in the major reservoirs
(intermediate and deep seawater).
PMID- 27509538
TI - Performance of Dynamically Simulated Reference Patterns for Cross-Correlation
Electron Backscatter Diffraction.
AB - High-resolution (or "cross-correlation") electron backscatter diffraction
analysis (HR-EBSD) utilizes cross-correlation techniques to determine relative
orientation and distortion of an experimental electron backscatter diffraction
pattern with respect to a reference pattern. The integrity of absolute strain and
tetragonality measurements of a standard Si/SiGe material have previously been
analyzed using reference patterns produced by kinematical simulation. Although
the results were promising, the noise levels were significantly higher for
kinematically produced patterns, compared with real patterns taken from the Si
region of the sample. This paper applies HR-EBSD techniques to analyze lattice
distortion in an Si/SiGe sample, using recently developed dynamically simulated
patterns. The results are compared with those from experimental and kinematically
simulated patterns. Dynamical patterns provide significantly more precision than
kinematical patterns. Dynamical patterns also provide better estimates of
tetragonality at low levels of distortion relative to the reference pattern;
kinematical patterns can perform better at large values of relative tetragonality
due to the ability to rapidly generate patterns relating to a distorted lattice.
A library of dynamically generated patterns with different lattice parameters
might be used to achieve a similar advantage. The convergence of the cross
correlation approach is also assessed for the different reference pattern types.
PMID- 27509539
TI - Nurse Practitioners have an Opportunity to Shape Health Care and Payment Reform.
PMID- 27509540
TI - The four R's of revising and resubmitting a manuscript.
PMID- 27509541
TI - Tracer methodology: an appropriate tool for assessing compliance with
accreditation standards?
AB - OBJECTIVES: Tracer methodology has been used by Accreditation Canada since 2008
to collect evidence on the quality and safety of care and services, and to assess
compliance with accreditation standards. Given the importance of this methodology
in the accreditation program, the objective of this study is to assess the
quality of the methodology and identify its strengths and weaknesses. METHOD: A
mixed quantitative and qualitative approach was adopted to evaluate consistency,
appropriateness, effectiveness and stakeholder synergy in applying the
methodology. An online questionnaire was sent to 468 Accreditation Canada
surveyors. RESULTS: According to surveyors' perceptions, tracer methodology is an
effective tool for collecting useful, credible and reliable information to assess
compliance with Qmentum program standards and priority processes. The results
show good coherence between methodology components (appropriateness of the
priority processes evaluated, activities to evaluate a tracer, etc.). The main
weaknesses are the time constraints faced by surveyors and management's lack of
cooperation during the evaluation of tracers. CONCLUSION: The inadequate amount
of time allowed for the methodology to be applied properly raises questions about
the quality of the information obtained. This study paves the way for a future,
more in-depth exploration of the identified weaknesses to help the accreditation
organization make more targeted improvements to the methodology. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27509542
TI - Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia
Reperfusion Injury.
AB - Purpose To evaluate whether noninvasive molecular imaging technologies targeting
myeloperoxidase (MPO) can reveal early inflammation associated with spinal cord
injury after thoracic aortic ischemia-reperfusion (TAR) in mice. Materials and
Methods The study was approved by the institutional animal care and use
committee. C57BL6 mice that were 8-10 weeks old underwent TAR (n = 55) or sham (n
= 26) surgery. Magnetic resonance (MR) imaging (n = 6) or single photon emission
computed tomography (SPECT)/computed tomography (CT) (n = 15) studies targeting
MPO activity were performed after intravenous injection of MPO sensors (bis-5
hydroxytryptamide-tetraazacyclododecane [HT]-diethyneletriaminepentaacetic acid
[DTPA]-gadolinium or indium 111-bis-5-HT-DTPA, respectively).
Immunohistochemistry and flow cytometry were used to identify myeloid cells and
neuronal loss. Proinflammatory cytokines, keratinocyte chemoattractant (KC), and
interleukin 6 (IL-6) were measured with enzyme-linked immunosorbent assay.
Statistical analyses were performed by using nonparametric tests and the Pearson
correlation coefficient. P < .05 was considered to indicate a significant
difference. Results Myeloid cells infiltrated into the injured cord at 6 and 24
hours after TAR. MR imaging confirmed the presence of ischemic lesions associated
with mild MPO-mediated enhancement in the thoracolumbar spine at 24 hours
compared with the sham procedure. SPECT/CT imaging of MPO activity showed marked
MPO-sensor retention at 6 hours (P = .003) that continued to increase at 24 hours
after TAR (P = .0001). The number of motor neurons decreased substantially at 24
hours after TAR (P < .01), which correlated inversely with in vivo inflammatory
changes detected at molecular imaging (r = 0.64, P = .0099). MPO was primarily
secreted by neutrophils, followed by lymphocyte antigen 6 complexhigh monocytes
and/or macrophages. There were corresponding increased levels of proinflammatory
cytokines KC (P = .0001) and IL-6 (P = .0001) that mirrored changes in MPO
activity. Conclusion MPO is a suitable imaging biomarker for identifying and
tracking inflammatory damage in the spinal cord after TAR in a mouse model. (c)
RSNA, 2016 Online supplemental material is available for this article.
PMID- 27509543
TI - Application of Modified Spin-Echo-based Sequences for Hepatic MR Elastography:
Evaluation, Comparison with the Conventional Gradient-Echo Sequence, and
Preliminary Clinical Experience.
AB - Purpose To (a) evaluate modified spin-echo (SE) magnetic resonance (MR)
elastographic sequences for acquiring MR images with improved signal-to-noise
ratio (SNR) in patients in whom the standard gradient-echo (GRE) MR elastographic
sequence yields low hepatic signal intensity and (b) compare the stiffness values
obtained with these sequences with those obtained with the conventional GRE
sequence. Materials and Methods This HIPAA-compliant retrospective study was
approved by the institutional review board; the requirement to obtain informed
consent was waived. Data obtained with modified SE and SE echo-planar imaging
(EPI) MR elastographic pulse sequences with short echo times were compared with
those obtained with the conventional GRE MR elastographic sequence in two patient
cohorts, one that exhibited adequate liver signal intensity and one that
exhibited low liver signal intensity. Shear stiffness values obtained with the
three sequences in 130 patients with successful GRE-based examinations were
retrospectively tested for statistical equivalence by using a 5% margin. In 47
patients in whom GRE examinations were considered to have failed because of low
SNR, the SNR and confidence level with the SE-based sequences were compared with
those with the GRE sequence. Results The results of this study helped confirm the
equivalence of SE MR elastography and SE-EPI MR elastography to GRE MR
elastography (P = .0212 and P = .0001, respectively). The SE and SE-EPI MR
elastographic sequences provided substantially improved SNR and stiffness
inversion confidence level in 47 patients in whom GRE MR elastography had failed.
Conclusion Modified SE-based MR elastographic sequences provide higher SNR MR
elastographic data and reliable stiffness measurements; thus, they enable
quantification of stiffness in patients in whom the conventional GRE MR
elastographic sequence failed owing to low signal intensity. The equivalence of
the three sequences indicates that the current diagnostic thresholds are
applicable to SE MR elastographic sequences for assessing liver fibrosis. (c)
RSNA, 2016.
PMID- 27509544
TI - Intravenous Gadoxetate Disodium Administration Reduces Breath-holding Capacity in
the Hepatic Arterial Phase: A Multi-Center Randomized Placebo-controlled Trial.
AB - Purpose To determine, in a multicenter double-blinded placebo-controlled trial,
whether maximal hepatic arterial phase breath-holding duration is affected by
gadoxetate disodium administration. Materials and Methods Institutional review
board approval was obtained for this prospective multi-institutional HIPAA
compliant study; written informed consent was obtained from all subjects. At
three sites, a total of 44 volunteers underwent a magnetic resonance (MR) imaging
examination in which images were acquired before and dynamically after bolus
injection of gadoxetate disodium, normal saline, and gadoterate meglumine,
administered in random order in a single session. The technologist and volunteer
were blinded to the agent. Arterial phase breath-holding duration was timed after
each injection, and volunteers reported subjective symptoms. Heart rate (HR) and
oxygen saturation were monitored. Images were independently analyzed for motion
artifacts by three radiologists. Arterial phase breath-holding duration and
motion artifacts after each agent were compared by using the Mann-Whitney U test
and the McNemar test. Factors affecting the above outcomes were assessed by using
a univariate, multivariable model. Results Arterial phase breath holds were
shorter after gadoxetate disodium (mean, 32 seconds +/- 19) than after saline
(mean, 40 seconds +/- 17; P < .001) or gadoterate meglumine (43 seconds +/- 21, P
< .001) administration. In 80% (35 of 44) of subjects, arterial phase breath
holds were shorter after gadoxetate disodium than after both saline and
gadoterate meglumine. Three (7%) of 44 volunteers had severe arterial phase
motion artifacts after gadoxetate disodium administration, one (2%; P = .62) had
them after gadoterate meglumine administration, and none (P = .25) had them after
saline administration. HR and oxygen saturation changes were not significantly
associated with contrast agent. Conclusion Maximal hepatic arterial phase breath
holding duration is reduced after gadoxetate disodium administration in healthy
volunteers, and reduced breath-holding duration is associated with motion
artifacts. (c) RSNA, 2016.
PMID- 27509545
TI - Service user involvement enhanced the research quality in a study using
interpretative phenomenological analysis - the power of multiple perspectives.
AB - AIM: The aim of this study was to examine how service user involvement can
contribute to the development of interpretative phenomenological analysis
methodology and enhance research quality. BACKGROUND: Interpretative
phenomenological analysis is a qualitative methodology used in nursing research
internationally to understand human experiences that are essential to the
participants. Service user involvement is requested in nursing research. DESIGN:
We share experiences from 4 years of collaboration (2012-2015) on a mental health
promotion project, which involved an advisory team. METHODS: Five research
advisors either with a diagnosis or related to a person with severe mental
illness constituted the team. They collaborated with the research fellow
throughout the entire research process and have co-authored this article. We
examined the joint process of analysing the empirical data from interviews. Our
analytical discussions were audiotaped, transcribed and subsequently interpreted
following the guidelines for good qualitative analysis in interpretative
phenomenological analysis studies. RESULTS: The advisory team became 'the
researcher's helping hand'. Multiple perspectives influenced the qualitative
analysis, which gave more insightful interpretations of nuances, complexity,
richness or ambiguity in the interviewed participants' accounts. The outcome of
the service user involvement was increased breadth and depth in findings.
CONCLUSION: Service user involvement improved the research quality in a nursing
research project on mental health promotion. The interpretative element of
interpretative phenomenological analysis was enhanced by the emergence of
multiple perspectives in the qualitative analysis of the empirical data. We argue
that service user involvement and interpretative phenomenological analysis
methodology can mutually reinforce each other and strengthen qualitative
methodology.
PMID- 27509546
TI - [Prospective study on tooth loss in a cohort of dentate elderly].
AB - The aim of this study was to assess factors associated with tooth loss in elderly
60 years or older during a four-year observation period. A representative cohort
of dentate elderly from the city of Sao Paulo, Brazil, participated in the study.
The outcome was teeth loss incidence from 2006 to 2010. Demographic and
socioeconomic characteristics, health services access and use, behavior, reported
diseases, cognitive status, functional status, state of dentition, and use of
dental prosthesis were recorded as independent variables in 2006 and the outcome
was measured in 2010. Negative binomial regression models were used.
Participation included 440 dentate elderly. Increased likelihood of tooth loss
was associated with use of two removable prostheses (RR = 1.57; 95%CI: 1.02
2.41), fair self-rated oral health (RR = 1.62; 95%CI: 1.11-2.36), bad/very bad
self-rated oral health (RR = 1.87; 95%CI: 1.11-3.17), male gender (RR = 1.74;
95%CI: 1.28-2.37), and living alone (RR = 2.03; 95%CI: 1.11-3.72).
PMID- 27509547
TI - [Spatial analysis of counting data with excess zeros applied to the study of
dengue incidence in Campinas, Sao Paulo State, Brazil].
AB - Dengue incidence occurs predominantly within city limits. Identifying spatial
distribution of the disease at the local level helps formulate strategies to
control and prevent the disease. Spatial analysis of counting data for small
areas commonly violates the assumptions of traditional Poisson models due to the
excessive amount of zeros. This study compared the performance of four counting
models used in mapping diseases: Poisson, negative binomial, zero-inflated
Poisson, and zero-inflated negative binomial. The methods were compared in a
simulation study. The models analyzed in the simulation were applied to a spatial
ecological study of dengue data aggregated by census tracts in the city of
Campinas, Sao Paulo State, Brazil, 2007. Spatial analysis was conducted with
Bayesian hierarchical models. The zero-inflated Poisson model showed the best
performance for estimating relative risk of dengue incidence in the census
tracts.
PMID- 27509548
TI - [A Street Clinic in a state capital in Northeast Brazil from the perspective of
homeless people].
AB - The objective of this study was to evaluate the Street Clinic strategy in Maceio,
Alagoas State, Brazil, from the perspective of its users. This was a qualitative
study in coverage areas of the Street Clinic in Maceio. Research subjects were 18
homeless individuals assisted by the clinic (10 men and 8 women), ranging from 20
to 40 years of age. Data were collected from September 2014 to February 2015
using a semi-structured interview. Content analysis was applied to the data and
identified two categories: the first, the Street Clinic as such, revealed the
strategy's critical points, challenges, and potentialities; the second showed the
Street Clinic as social support, affect, and hope for change for the homeless.
The strategy was rated positively by users, providing social support on health
problems and other daily issues.
PMID- 27509549
TI - [Are there differences between paid women workers and housewives in health
related quality of life?].
AB - Considering the lack of Brazilian studies on the relationship between
participation in the labor market and health-related quality of life (HRQL) in
women, the objectives were to verify whether there is an association between paid
work versus no paid work and HRQL in women, and whether socioeconomic status
modifies this association. This was a population-based cross-sectional study with
a sample of 668 women 18 to 64 years of age from the Campinas Health Survey
(ISACamp 2008/2009), using SF-36 to assess HRQL. Being a housewife was associated
with worse HRQL, especially in mental domains, but this association was modified
by socioeconomic status. In the middle and low schooling and family income
strata, housewives showed worse HRQL than paid women workers, but there was no
difference between the two groups in the high schooling and high income strata.
Housewives' worse HRQL emphasizes the importance of public policies to expand
opportunities for women's participation in the labor market and access to
education.
PMID- 27509550
TI - [Use of causal diagrams in Epidemiology: application to a situation with
confounding].
AB - Epidemiological research still rarely uses causal diagrams, despite growing
recognition of their explanatory potential. One possible reason is that many
research programs involve themes in which there is a certain degree of
uncertainty as to mechanisms in the processes that generate the data. In this
study, the relationship between occupational stress and obesity is used as an
example of the application of causal diagrams to questions related to
confounding. The article presents the selection stages for variables in
statistical adjustment and the derivation of a causal diagram's statistical
implications. The main advantage of causal diagrams is that they explicitly
reveal the respective model's underlying hypotheses, allowing critical analysis
of the implications and thereby facilitating identification of sources of bias
and uncertainty in the epidemiological study's results.
PMID- 27509551
TI - Causal diagrams: back to the future for Brazilian epidemiology.
PMID- 27509552
TI - [Hepatitis C incidence in hemodialysis patients in Brazil from 2000 to 2003].
AB - The study aimed to estimate the incidence of HCV seroconversion in hemodialysis
patients in the Brazilian Unified National Health System (SUS). This was a
prospective, non-concurrent study using patients' data identified by
deterministic and probabilistic record linkage in the SUS information system. The
study included 47,079 patients started on hemodialysis between January 1, 2000,
and December 31, 2003, followed until seroconversion or conclusion of the study
in 2004. Three percent of hemodialysis patients HCV-seroconverted (1.7 per 100
patient-years). Increased risk of HCV seroconversion was associated with age,
glomerulonephritis, geographic region, HIV-positivity, and dialysis service. The
observed HCV seroconversion rate was similar to that in developed countries,
highlighting evidence of transmission among hemodialysis patients.
PMID- 27509553
TI - [Dimensional structure of the Brazilian version of the s-EMBU instrument for
measuring parental educational practices in adolescents].
AB - The aim of this study was to assess the dimensional structure of the s-EMBU, used
to measure parental educational practices in adolescents. The sample included 487
students from Greater Metropolitan Rio de Janeiro, Brazil, in 2013. Mean age was
14 years, and 47% were girls. The original dimensional structure was assessed by
confirmatory factor analysis (CFA). The study also applied exploratory structural
equation modeling (ESEM). CFA adjustment was unsatisfactory. In light of the
ESEM, the most parsimonious solution concerned the three-factor model (RMSEA =
0.03, CFI = 0.97, and TLI = 0.96), but various items in the overprotection
dimension showed higher factor loads in the rejection dimension. The items in the
rejection and emotional warmth dimensions proved more appropriate. In Brazil, s
EMBU partially captures the proposed dimensions for measuring parental
educational practices in adolescents. Emotional warmth had its dimensional
structure confirmed, but rejection and especially overprotection require further
refinement.
PMID- 27509554
TI - [Comprehensiveness and healthcare technologies: a narrative on conceptual
contributions to the construction of the comprehensiveness principle in the
Brazilian Unified National Health System].
AB - Comprehensiveness is the most challenging principle for building health reform in
the Brazilian Unified National Health System (SUS). This study aims to identify
critical moments in the conceptual debate on comprehensiveness and its
contributions to reflection on healthcare technologies in the SUS. The essay
addresses some conceptual constructs that approach comprehensiveness as an
underlying principle in health programs and actions at various levels and in
various dimensions of the healthcare organization - from intersubjective
interactions to the organization of regional networks. The study was based on a
non-systematic literature review on comprehensiveness and related themes in the
Brazilian public health field in the last five decades. The study proposed a
chronology/typology spanning the 1960s to the 2010s, divided into four
significant periods or categories. The narrative is not intended to be
exhaustive, but to build a comprehensive reference base capable of contributing
to analyses, assessments, and debates on healthcare organization in the SUS
according to the comprehensiveness principle.
PMID- 27509555
TI - Predisposing, enabling and need-for-care predictors of adolescents' intention to
use sexual health services.
AB - BACKGROUND: The study aimed to understand the influence of predisposing, enabling
and need-for-care factors on adolescents' intention to use sexual health
services, using Andersen's Behavioural Model of Health Service Utilisation to
organise and test these factors. METHODS: A sample of predominantly Hispanic
teens (n=600) in Los Angeles, California completed a self-report survey about
their sexual health knowledge, beliefs, intentions, and behaviours. Hierarchical
regression modelling was used to examine the incremental influences on
adolescents' intention to use sexual health services of: 1) predisposing
sociodemographic factors; 2) predisposing knowledge and beliefs about sexual
health; 3) enabling factors regarding perceived access to sexual health services;
and 4) a need-for-care factor (sexual experience). RESULTS: Adolescents reported
high intentions to use sexual health services (3.25 on a 4-point scale), yet only
42% reported knowing where to access services. Sexual health knowledge and
beliefs significantly predicted adolescents' intention to use services beyond the
effect of sociodemographics (P<0.001). Enabling factors indicating awareness of
and importance attributed to accessibility significantly predicted intention to
use services incremental to predisposing factors (P<0.001). However, need for
care - that is, sexual experience - was not statistically associated with
intention to use services (P=0.402). CONCLUSIONS: Sexual health interventions are
needed to provide sexual health information, promote positive beliefs about
health care, and ensure adolescents' awareness of and access to sexual health
services.
PMID- 27509556
TI - President's Message.
PMID- 27509557
TI - Medicine Development: What's My Responsibility?
PMID- 27509558
TI - Balancing the Risk: Increasing Inpatient Ambulation Without Increasing Falls.
PMID- 27509559
TI - Measurement in Intervention Research.
PMID- 27509560
TI - Making the Journey from Opioid and Heroin Addiction: One Map for the Clinical
Nurse Specialist.
PMID- 27509561
TI - Polishing Your Presence Online: Wise Use of Social Media to Enhance Your
Reputation.
PMID- 27509562
TI - Evaluation of a Regional Australian Nurse-Led Parkinson's Service Using the
Context, Input, Process, and Product Evaluation Model.
AB - OBJECTIVE: A nurse-led Parkinson's service was introduced at Canberra Hospital
and Health Services in 2012 with the primary objective of improving the care and
self-management of people with a diagnosis of Parkinson's disease (PD) and
related movement disorders. Other objectives of the Service included improving
the quality of life of patients with PD and reducing their caregiver burden,
improving the knowledge and understanding of PD among healthcare professionals,
and reducing unnecessary hospital admissions. This article evaluates the first 2
years of this Service. METHODS: The Context, Input, Process, and Product
Evaluation Model was used to evaluate the Parkinson's and Movement Disorder
Service. CONTEXT: The context evaluation was conducted through discussions with
stakeholders, review of PD guidelines and care pathways, and assessment of
service gaps. Input: The input evaluation was carried out by reviewing the
resources and strategies used in the development of the Service. PROCESS: The
process evaluation was undertaken by reviewing the areas of the implementation
that went well and identifying issues and ongoing gaps in service provision.
Product: Finally, product evaluation was undertaken by conducting stakeholder
interviews and surveying patients in order to assess their knowledge and
perception of value, and the patient experience of the Service. Admission data
before and after implementation of the Parkinson's and Movement Disorder Service
were also compared for any notable trends. RESULTS: CONTEXT: Several gaps in
service provision for patients with PD in the Australian Capital Territory were
identified, prompting the development of a PD Service to address some of them.
Input: Funding for a Parkinson's disease nurse specialist was made available, and
existing resources were used to develop clinics, education sessions, and outreach
services. PROCESS: Clinics and education sessions were implemented successfully,
with positive feedback from patients and healthcare professionals. However,
outreach services were limited because of capacity constraints on the Parkinson's
disease nurse specialist. Product: The Service has filled an important health
need in the local context; 98.3% of patients surveyed reported that the Service
met their needs and helped them understand their care plan, achieving the primary
objective of improving patient self-management. Interviews with stakeholders
provided positive feedback about the value and usefulness of the Service, and
healthcare professionals reported improvement in their knowledge about PD
management. The evaluation also identified ongoing gaps in service provision and
highlighted areas for potential improvement. No discernible trends in admission
rates before and after the implementation of the Service were identified.
CONCLUSION: The introduction of a nurse-led PD service has had a positive impact
on the provision of care for patients with PD and is a valued service. The
evaluation highlighted some ongoing gaps in service provision and has generated
some recommendations to address these.
PMID- 27509563
TI - From Hospital to Ambulatory Care: Realigning the Practice of Clinical Nurse
Specialists.
AB - PURPOSE/OBJECTIVES: This article describes how a large healthcare organization
expanded the practice of clinical nurse specialists from the hospital to the
ambulatory setting. BACKGROUND: Clinical nurse specialist practice traditionally
focused on actualizing the 3 spheres of influence (patient, nurse, and
organization) in the hospital setting. RATIONALE: Changes in the healthcare
system shifting patient care to the ambulatory setting created opportunities for
clinical nurse specialists to improve patient outcomes in this setting.
DESCRIPTION: An innovation framework from the Mayo Clinic Center for Innovation
based on inspiration, generation of ideas, experimenting, and diffusion was used
to assess and prioritize the work of clinical nurse specialists in the ambulatory
setting. OUTCOMES: Clinical nurse specialists became integral members of hospital
and ambulatory nursing leadership. In the ambulatory setting, they are partnering
to standardize patient care, providing tools for nurses to practice to full
scope, and identifying and providing solutions for patient safety issues.
CONCLUSION: Aligning clinical nurse specialists in the hospital and ambulatory
care settings allows partnership with multidisciplinary teams to ensure that
evidence-based practices and standardized care are infused across the continuum
of care. IMPLICATIONS: Evidence-based practices and standardized care encourage
nurses to practice to full scope and focus on improved patient outcomes.
PMID- 27509564
TI - Integrating Retired Registered Nurses Into a New Graduate Orientation Program.
AB - PURPOSE: The project goal of was to decrease new graduate nurse (NGN) attrition
during the first year of employment by improving communication skills and
providing additional mentoring for NGNs employed in a community hospital located
in a rural area. DESCRIPTION OF PROJECT: All NGNs participate in the Versant
Residency Program. Even with this standardized residency program, exit interviews
of NGNs who resigned during their first year of employment revealed 2 major
issues: communication problems with patients and staff and perceived lack of
support/mentoring from unit staff. A clinical nurse specialist-led nursing team
developed an innovative program integrating retired nurses, Volunteer Nurse
Ambassadors (VNAs), into the Versant Residency Program to address both of those
issues. OUTCOME: All NGNs mentored by a retired nurse remain employed in the
hospital (100% retention). Before the VNA program, the retention rate was 37.5%.
Both the NGNs and VNAs saw value in their mentor-mentee relationship. There have
been no critical incidences or failure to rescue events involving NGNs mentored
by a VNA. CONCLUSION: Use of VNAs to support NGNs as they adjust to the staff
nurse role can prevent attrition during their first year of nursing practice by
providing additional support to the NGN.
PMID- 27509565
TI - Two Hours of Teamwork Training Improves Teamwork in Simulated Cardiopulmonary
Arrest Events.
AB - PURPOSE/AIM: Teamwork during cardiopulmonary arrest events is important for
resuscitation. Teamwork improvement programs are usually lengthy. This study
assessed the effectiveness of a 2-hour teamwork training program. DESIGN: A
prospective, pretest/posttest, quasi-experimental design assessed the teamwork
training program targeted to resident physicians, nurses, and respiratory
therapists. METHODS: Participants took part in a simulated cardiac arrest. After
the simulation, participants and trained observers assessed perceptions of
teamwork using the Team Emergency Assessment Measure (TEAM) tool (ratings of 0
[low] to 4 [high]). A debriefing and 45 minutes of teamwork education followed.
Participants then took part in a second simulated cardiac arrest scenario.
Afterward, participants and observers assessed teamwork. RESULTS: Seventy-three
team members participated-resident physicians (25%), registered nurses (32%), and
respiratory therapists (41%). The physicians had significantly less experience on
code teams (P < .001). Baseline teamwork scores were 2.57 to 2.72. Participants'
mean (SD) scores on the TEAM tool for the first and second simulations were 3.2
(0.5) and 3.7 (0.4), respectively (P < .001). Observers' mean (SD) TEAM scores
for the first and second simulations were 3.0 (0.5) and 3.7 (0.3), respectively
(P < .001). Program evaluations by participants were positive. CONCLUSIONS: A 2
hour simulation-based teamwork educational intervention resulted in improved
perceptions of teamwork behaviors. Participants reported interactions with other
disciplines, teamwork behavior education, and debriefing sessions were beneficial
for enhancing the program.
PMID- 27509566
TI - Clinical Nurse Specialist Roles in Conducting Research: Changes Over 3 Years.
AB - PURPOSE: The aim of this study is to describe clinical nurse specialists'
characteristics, interest, confidence, motivators, and barriers in conducting
research. DESIGN: This study was a descriptive, multicohort design. METHODS:
Clinical nurse specialists were recruited electronically through national and
local organizations to complete anonymous surveys 3 times, over 3 years.
Comparative analyses included chi and Kruskal-Wallis tests. RESULTS: Of 2052
responders (initial, n = 629; 18 months, n = 465; and 3 years, n = 958), mean
(SD) participant age was 50.3 (9.3) years. Overall, 41.7% of participants were
involved as principal or coinvestigators in research. Interest in conducting
nursing research (on a 0-100 scale) was 61.1 (38.4) and was lowest among the 18
month time point participant group (score, 39.1 [32.2]) and highest at the 3-year
time point (68.3, [30.7]; P < .001). Confidence in conducting research,
discussion of statistics, and perceptions of motivators and barriers to
conducting research did not differ across time period groups. Access to
literature and mentors and research knowledge were the most prevalent barriers to
conducting research. CONCLUSIONS: Less than 42% of clinical nurse specialists
conducted research and the rate did not change between different time groups.
Access and knowledge barriers to conducting research were prominent. Workplace
leaders need to consider resources and support of academic educational
opportunities to increase research conduct by clinical nurse specialists.
PMID- 27509567
TI - Prescriptive Authority and Independent Practice Progress for the Clinical Nurse
Specialist-Changes Since 2010.
PMID- 27509568
TI - Disruptive Innovation in Graduate Nursing Education: Tipping the Scales for
Online Education.
PMID- 27509569
TI - Dance 'til the Buffalo Come.
PMID- 27509570
TI - "One Flare at a Time": Adaptive and Maladaptive Behaviors of Women Coping With
Inflammatory Bowel Disease and Irritable Bowel Syndrome.
AB - PURPOSE: The purpose of this investigation is to study the lived experiences of
female postsecondary students diagnosed with inflammatory bowel disease and/or
irritable bowel syndrome. METHODS: Nine women between the ages of 18 and 26 years
were recruited to participate in this study. Participants completed an informed
consent form and background questionnaire before completing a semi-structured one
on-one interview. This interview explored the lived experiences of these
individuals in relation to condition management. RESULTS: Three salient themes
that emerged from the data included (1) it can add to my life; (2) why me: my
condition runs my life; and (3) I'm doing the best I can with what I have. The
salient theme of I'm doing the best I can with what I have, the theme addressed
in this article, was subdivided into adaptive and maladaptive coping behaviors.
Reasons for the use of these behaviors included to avoid triggers or flare
ups/harmful effects, to achieve instant relief/pleasure, to respond to
environmental pressures, and to become accustomed to dealing with the everyday
hassles of their conditions. CONCLUSION: Community health nurses may become part
of the solution to help women with inflammatory bowel disease and irritable bowel
syndrome find more adaptive coping behaviors. Other implications are discussed.
PMID- 27509571
TI - The Null Effect of Chewing Gum During Hemodialysis on Dry Mouth.
AB - AIMS AND OBJECTIVES: The study was conducted to determine the effect of chewing
gum during hemodialysis on dry mouth and its symptoms. BACKGROUND: The imposition
of fluid restriction and the use of medications that reduce saliva production may
lead to dry mouth. DESIGN: This study is a randomized, controlled, single-blind,
crossover experimental study. METHODS: The subjects consisted of 61 hemodialysis
patients recruited from 4 dialysis centers in southern Turkey. The data were
collected using a Patient Identification Form, a Form for Assessing the Symptoms
of Dry Mouth, and a Patient Follow-up Form. Saliva samples were obtained for
analysis of flow rates. RESULTS: The salivary flow rates of the patients
increased during the first hour on the day when gum was chewed, and this increase
was statistically significant. However, no significant difference was found
between the salivary flow rates at the 0- and 4-hour time points on the day when
gum was chewed (P > .05). In addition, the salivary pH values were in the normal
range on both days, although the pH values tended to be more acidic on the day
when gum was not chewed. CONCLUSIONS: Overall, it was found that chewing gum for
15 minutes each hour during a hemodialysis session did not increase the saliva
amount, maintain the pH value of the saliva within a normal range, or control dry
mouth symptoms.
PMID- 27509572
TI - Making the Journey From Opioid and Heroin Addiction: One Map for the Clinical
Nurse Specialist.
PMID- 27509573
TI - Gestational Age and the Risk of Maternal Breast Cancer: A Population-Based Case
Control Study.
AB - There is limited evidence that the gestational age at delivery may influence the
risk of maternal breast cancer. While extreme prematurity has been suggested to
increase the risk, there seems to be no study available so far that investigates
the due effects of a late delivery. This research aimed to identify the impact of
both preterm and late deliveries on the risk of maternal breast cancer within a
period of 5 years after birth. Our dataset was created by linking data from the
Nevada Cancer Registry database (1995-2008) and the birth certificates issued by
the Nevada State Health Division (1994-2003). The study cohort consisted of
213,250 women who gave birth from January 1, 1994 to December 31, 2003. We
performed a nested population-based case-control study on 126 Nevada mothers with
a first lifetime breast cancer diagnosed from January 1, 1995 through December
31, 2003, and 504 Nevada cancer-free mothers. Women with pregnancies who
progressed beyond 40 weeks of gestation were at a significantly lower risk of
developing breast cancer for the 5-year period following a delivery, when
compared to women who delivered at 37-40 weeks of gestation (OR: 0.33, 95% CI:
0.11-0.92) in a multivariate model. Additional pregnancy characteristics did not
significantly predict the risk of maternal breast cancer. Pregnancies that
extended beyond 40 weeks of gestation were strongly associated with a lower
likelihood of premenopausal breast cancer. Biological plausibility for this
association may correspond to the fact that as pregnancy develops into more
advanced stages, mammary cells have more time to attain complete differentiation
and maturation; a process that starts early in the third trimester.
PMID- 27509574
TI - A cost utility analysis of the clinical algorithm for nasogastric tube placement
confirmation in adult hospital patients.
AB - AIM: The aim of this study was to evaluate the effectiveness of pH paper testing
of aspirate and chest x-ray for determining nasogastric tube (NGT) placement in
terms of cost and patient outcome. BACKGROUND: Nasogastric tubes are frequently
used in clinical practice, however during insertion the practitioner is blinded
as to the precise final location. Despite robust checking procedures, recognized
patient morbidity and mortality associated with this procedure have resulted in
national safety alerts prompting the revision of all NGT care clinical
guidelines. DESIGN: Cost utility analysis using economic modelling. METHODS: A
decision tree was built and populated with effectiveness data gathered from a
systematic search of the extant literature. Specificity, pooled sensitivity and
event probabilities were calculated using statistical software. Patient outcome
was measured in terms of quality of life. Health state utilities were gathered
from a sample (n = 23) of adult surgical patients using a recognized instrument.
Cost data were gathered using published sources. The study adopted a third party
payer perspective in a Scottish context and was completed in June 2013. RESULTS:
The results confirm that the current UK algorithm advocated by the National
Patient Safety Agency appears to offer the most cost effective approach to NGT
confirmation in terms of cost and patient outcome. Sensitivity analyses indicate
that these findings may be significantly altered by tube aspiration success and
the rates of chest x-ray interpretation errors. CONCLUSION: The results confirm
current UK recommendations and have wider policy implications for those areas,
whereby chest x-ray is recommended as the first and only acceptable confirmation
approach.
PMID- 27509575
TI - Mismatch repair system proteins in oral benign and malignant lesions.
AB - Different environmental agents may cause DNA mutations by disrupting its double
strand structure; however, even normal DNA polymerase function may synthesize
mismatch nucleotide bases, occasionally demonstrating failure in its proofreading
activity. To overcome this issue, mismatch repair (MMR) system, a group of
proteins specialized in finding mispairing bases and small loops of insertion or
deletion, works to avoid the occurrence of mutations that could ultimately lead
to innumerous human diseases. In the last decades, the role of MMR proteins in
oral carcinogenesis and in the development of other oral cavity neoplasms has
grown, but their importance in the pathogenesis and their prognostic potential
for patients affected by oral malignancies, especially oral squamous cell
carcinoma (OSCC), remain unclear. Therefore, in this manuscript we aimed to
review and critically discuss the currently available data on MMR proteins
expression in oral potentially malignant lesions, in OSCC, and in other oral
neoplasms to better understand their relevance in these lesions.
PMID- 27509576
TI - Washing of platelets can be fully automated using a closed-system cell processor
and BRS-A platelet additive solution.
AB - This study evaluated the in vitro properties of platelets (PLTs) washed with BRS
A additive solution in the Haemonetics ACP215 automated processing system. Two
washing modes, 'manually/automatically adding ACD-A to BRS before/during the
washing process', represented the control and test groups, respectively. Outcomes
were compared over 7 days of storage (n = 7, for both). PLT recovery following
washing processing (26-27 min) was 86.2 +/- 1.7% and 86.0 +/- 2.2% and plasma
protein removal was 98.8 +/- 0.3% and 99.0 +/- 0.2% in the control and test
groups, respectively (not significant). Both groups exhibited comparable in vitro
properties.
PMID- 27509577
TI - A rapidly enlarging nodule on the scalp in an infant.
PMID- 27509579
TI - Marital quality, marital dissolution, and mortality risk during the later life
course.
AB - This study examines the relationship between later-life marital quality, marital
dissolution, and mortality using discrete-time event history models with data
from nine waves (1992-2008) of the Health and Retirement Study (n = 7388).
Results show marital status is more important for men's mortality risk than
women's, whereas marital quality is more important for women's survival than
men's. Being widowed or divorced more than two years raises mortality risk for
men, but later-life marital dissolution is not significantly associated with
women's mortality risk, regardless of the type of dissolution or length of time
since it occurred. Low-quality marital interaction is negatively related to
women's odds of death, but none of the marital quality measures are significantly
associated with mortality for men. Marital satisfaction moderates the
relationship between widowhood and mortality for women, but the relationship
between marital dissolution and mortality is similar for men regardless of
marital quality prior to divorce/widowhood. Results suggest the importance of
accounting for both marital status and marital quality when examining older
individuals' mortality risk.
PMID- 27509578
TI - Hypogammaglobulinemia and risk of severe infection in kidney transplant
recipients.
AB - BACKGROUND: Recent data have outlined a link between hypogammaglobulinemia (HGG)
and infection risk and suggested that HGG correction may decrease post-transplant
infections. METHODS: We analyzed the risk factors of HGG and the relationship
between HGG and the risk of severe infection in a cohort of 318 kidney transplant
recipients (KTR) who were transplanted between 2003 and 2013. Immunoglobulin (Ig)
concentration was measured prospectively at day 15 (D15), month 6 (M6), month 12
(M12), and month 24 (M24) post transplant. RESULTS: The prevalence of IgG HGG was
56% and 36.8% at D15 and M6, respectively. Age was the sole identified risk
factors for D15 IgG HGG (odds ratio [OR] 1.02, P = 0.019). Risk factors for M6
IgG HGG were the presence of D15 IgG HGG (OR 6.41, P < 0.001) and treatment of
acute rejection (OR 2.63, P = 0.014). Most infections occurred between D15 and M6
post transplant. Only age (hazard ratio 1.03, P < 0.001) was identified as a risk
factor of infection between D15 and M6 post transplant. Survival free of
infection (overall infections and bacterial or viral infections) did not differ
significantly between patients with or without D15 IgG HGG. Only septicemia
occurring between M6 and M12 post transplant was more frequently observed in
patients with HGG. The low prevalence of severe HGG (<400 mg/dL) did not allow
conclusions on the infectious risk associated with this patient subgroup.
CONCLUSIONS: This study does not support the existence of a strong link between
post-transplant HGG and the risk of severe infections in KTR. Correction of HGG
to minimize the risk of severe infections in KTR is thus questionable and needs
to be reevaluated in prospective studies.
PMID- 27509580
TI - The International Society of Nephrology (ISN). Roles & challenges in Africa and
other resource-limited communities.
AB - ISN (the International Society of Nephrology) is a global organization with more
than 9,000 members in 130 countries. The ISN's mission is to "advance the
diagnosis, treatment, and prevention of kidney diseases in the developing and
developed world". ISN delivers this mission in low-resource settings through its
five education and training programs available exclusively to low- and middle
income countries. These programs are designed to enable sustainable growth in
capacity in nephrology and related disciplines to provide the basis for the
improvement of care for kidney patients worldwide. ISN also directs its efforts
towards advocacy for kidney health and kidney care, seeking to increase
understanding of kidney disease among the general population, health
professionals, and health policy makers. Such advocacy is challenging because of
the complexity of kidney health messages; there is a need to emphasize affordable
healthcare solutions for prevention and treatment of acute kidney injury (AKI),
as well as the prevention and management of chronic kidney disease (CKD), and the
provision of renal replacement therapy (both chronic dialysis and kidney
transplantation) that is both affordable and ethically acceptable.
PMID- 27509581
TI - Kidney disease in disadvantaged populations: An unconquered challenge.
PMID- 27509582
TI - Burden of end-stage renal disease (ESRD) in Latin America.
AB - INTRODUCTION: End-stage renal disease (ESRD) represents a major challenge for
Latin America (LA). Epidemiological information needed to assist in the
development of ESRD care in the region. The Latin American Dialysis and Renal
Transplant Registry (RLADTR), has published several reports and its continuity
has implied a sustained effort of the entire LA Nephrology community. This paper
summarizes the results corresponding to year 2012. METHODS: Our methods have been
reported previously. Participant countries complete an annual survey collecting
data on incident and prevalent patients undergoing renal replacement treatment
(RRT) in all modalities. RESULTS: 20 countries participated in the surveys, more
than 90% of the Latin America. The prevalence of ESRD under RRT in LA increased
from 119 patients Per million population (pmp) in 1991 to 661 pmp in 2012. HD
continues to be the treatment of choice in the region (82%). A wide rate
variation in incidence is observed: from 472.7 in Jalisco (Mexico) to 14 pmp in
Guatemala. Diabetes remained the leading cause of ESRD. The most frequent cause
of death was cardiovascular. There is a wide rate variation of nephrologist by
country, from 1.8 pmp in Honduras to 45.2 pmp in Cuba. DISCUSSION: The
heterogeneity or even absence of registries in some LA countries is congruent
with the inequities in access to RRT in such countries, as well as the
availability of qualified personnel. The SLANH is currently running training
programs as well as cooperation programs between LA countries to help the least
developed start ESRD programs. In this spirit, RLADTR is training personnel to
carry out dialysis and transplant registries in LA.
PMID- 27509583
TI - From man to fish: What can Zebrafish tell us about ApoL1 nephropathy?
AB - BACKGROUND: Risk variant Apolipoprotein L1 (G1/G2) are strongly associated with a
spectrum of kidney disease in people of recent African descent. The mechanism of
ApoL1 nephropathy is unknown. Podocytes and/or endothelial cells are the presumed
target kidney cells. Given the close homology in structure and function of
zebrafish (ZF) pronephros and human nephron, we studied the effect of podocyte
specific or endothelium-specific expression of ApoL1 (G0, G1, or G2) on the
structure and function of ZF pronephros. METHODS: Wild type (G0) or risk variant
ApoL1 (G1/G2) were expressed in podocyte-specific or endothelium-specific under
podocin/Flk promoters, respectively, using Gal4-UAS system. Structural pronephric
changes were studied with light and electron microscopy (EM). Proteinuria was
assayed by measuring renal excretion of GFP-vitamin D binding protein. Puromycin
aminonucleoside (PAN) was used as inducer of podocyte injury. RESULTS:
Endothelial-specific transgenic expression of G1/G2 is associated with
endothelial injury indicated by endothelial cell swelling, segmental early double
contours, and loss of endothelium fenestrae. Podocyte specific expression of G1
is associated with segmental podocyte foot process effacement and irregularities
relative to G0. Despite the histological changes, the expression of G1/G2 alone
in podocyte or endothelium compartment is not associated with edema, proteinuria,
or gross whole fish phenotype. Moreover, PAN produced equal pericardial edema in
all transgenic fish as well as nontransgenic controls. CONCLUSIONS: Transgenic
expression human ApoL1 (G1/G2) is associated with histologic abnormalities in ZF
glomeruli but is insufficient to cause quantifiable renal dysfunction. This
finding supports the necessity of a "second hit" in the pathogenesis/progression
of ApoL1-associated nephropathy.
PMID- 27509584
TI - Fever, thrombocytopenia, and AKI-A profile of malaria, dengue, and leptospirosis
with renal failure in a South Indian tertiary-care hospital.
AB - INTRODUCTION: In the tropics, the triad of fever, thrombocytopenia, and AKI
portends a grim prognosis with high mortality and a severe strain on already
stretched resources. Malaria, dengue, and leptospirosis account for most cases.
We undertook a review of cases to determine factors accounting for adverse
prognosis. METHODS: All patients presenting to the emergency room (ER) with a
history of fever, thrombocytopenia, and renal failure were included in the study.
Patients were followed until discharge or death, and end points looked at were 1
week and 30-day mortality, and renal function upon discharge. Parameters like
liver function test (LFT), renal function, and platelet count upon discharge were
also documented. RESULTS: A total of 43 patients was included in the study. Mean
age was 42.5 years with 86% males. Mean APACHE and SOFA scores on admission were
23.89 and 15.42, respectively. Mean admission platelet counts were 41,000. Mean
serum creatinine was 4.1, and bilirubin was 9.94. A platelet count of < 34,000,
serum creatinine of > 4, albumin of > 2.3, SOFA score of > 20, and APACHE score
of > 32.2 were significantly predictive of 1 week mortality. Need for mechanical
ventilation, oliguria on admission, and need for dialysis all were highly
predictive of 30-day mortality. In addition, a serum bicarbonate of < 12, INR of
> 1.5, hemoglobin of < 9.5 were highly predictive of higher 30 day mortality.
Overall, 1-week mortality was 16.3%, of which 48% was accounted for by patients
with leptospirosis. CONCLUSIONS: Factors like low platelet count, oliguria, need
for dialysis, high APACHE and SOFA scores on admission, need for mechanical
ventilation, and low serum albumin portend a grave prognosis. There is need for
randomized control trials (RCT) to further determine adverse prognostic factors
in this subsect of patients.
PMID- 27509585
TI - Spectrum of kidney diseases in Africa: malaria, schistosomiasis, sickle cell
disease, and toxins.
AB - Kidney diseases have assumed epidemic proportions in both developed and
developing countries, particularly chronic kidney disease (CKD). While treatment
modalities are available and accessible in developed economies with improvement
in outcomes, survival, and quality of life, they are either unavailable or
inaccessible in nations with emerging economies, particularly in sub-Saharan
Africa (SSA), with an attendant worsening outcome and survival for CKD patients.
The epidemiology of CKD in SSA has revealed that it preferentially affects adults
in their economically productive years, usually below the age of 50 years, with
consequent drain on the economy. This derives mainly from the major etiologies in
the region, which are infection-induced chronic glomerulonephritis and
hypertension, compounded by poverty as well as societal and health
underdevelopment, poor resource allocation to health, and underdeveloped health
infrastructures. This has made preventive nephrology a major goal in the sub
region, although those who have already developed CKD must be managed up to
tertiary levels. In this review, we assessed the contributions of parasitic
diseases (i.e., malaria and schistosomiasis), sickle cell disease and
nephrotoxins with the aim of espousing their contributions to the burden of
kidney disease, and proposing management options with the goal of ultimately
reducing the burden of kidney disease in these disadvantaged populations.
PMID- 27509586
TI - Renal histology patterns in a prospective study of nephrology clinics in Lagos,
Nigeria.
AB - BACKGROUND: The burden of chronic kidney disease (CKD) in Nigeria is quite
alarming. The prevalence of CKD ranges from 11 - 23.5%. Hypertension and chronic
glomerulonephritis (CGN) remain the two leading causes of CKD in Nigeria. The
etiology of CKD in many of these patients remains unknown, as few biopsies are
done. In order to demystify the various glomerular diseases that culminate in
CGN, performing a kidney biopsy offers a ray of hope. Few studies on renal
biopsies have emanated from Nigeria; this study, however, is unique as the
histopathological analysis involves light, immunofluorescence, and electron
microscopies. METHODS: This study involved two teaching hospitals in Lagos.
Patients from these centers, who met the inclusion criteria, underwent real-time
renal biopsy; after providing written informed consent. RESULTS: Among the 52
patients analyzed 26, (50%) were males. The mean age was 31.7 +/- 12.8, with age
range of 13 - 56 years. The most common indication for kidney biopsy was
nephrotic syndrome, accounting for 73%. Focal segmental glomerulosclerosis (FSGS)
was the most frequent histopathological diagnosis seen in 25 patients (48.1%).
CONCLUSION: The findings from this study highlight the role that renal biopsy
plays in making a concrete diagnosis in nephrology practice in a developing
country like Nigeria. As almost 80% of the study population was made up of
patients with FSGS and lupus nephritis, it remains to be determined by further
studies among our patients, the role that Apolipoprotein L1 (APOL 1) gene
mutation will play in the etiology of renal diseases in Nigeria.
PMID- 27509587
TI - Advances and challenges in renal transplantation in Latin America.
AB - Latin America is a region made up of 33 countries that share many characteristics
with each other. Since the first kidney transplant in Argentina in 1957, most of
the Latin American countries have had a continuous increase in renal transplant
activity, accounting for an increase in the total number of kidney transplants
over time. In the last years, several advances have been made in the area of
renal transplantation in Latin America: There are transplantation activities in
almost all countries, the kidney transplantation rate from deceased donors has
steadily increased, and almost all the countries have an appropriate legislation
for transplantation activity. But much remains to be done to increase the kidney
transplantation rate in order to cover the current demand. This could be achieved
by ensuring unlimited access to renal transplantation, by improving deceased
donor programs to match the increasing burden of chronic diseases, and by
incorporating new technology, new tools, and more trained people in transplant
programs.
PMID- 27509588
TI - Correlation between volume overload, chronic inflammation, and left ventricular
dysfunction in chronic kidney disease patients.
AB - BACKGROUND: Fluid overload is common in chronic kidney disease (CKD) patients,
potentially driving chronic inflammation and left ventricular dysfunction. We
investigated the association between volume overload, chronic inflammation, and
left ventricular dysfunction across subgroups of CKD patients. METHODS: The study
included 160 participants, comprising peritoneal dialysis (PD), hemodialysis
(HD), stage-3 CKD patients, and age- and sex-matched controls (40 in each group).
Fluid status was assessed using a body composition monitor (BCM); serum
endotoxin, lipopolysaccharide binding protein (LBP), C-reactive protein (CRP).
and interleukin-6 (IL-6) levels were measured as markers of inflammation.
Echocardiography was done to assess left ventricular dimension and function.
RESULTS: Endotoxemia and volume overload were common across the spectrum of CKD
patients and were aggravated by worsening kidney function. Among HD cohorts,
postdialysis endotoxemia was increased among patients with dialysis-induced
hemodynamic instability and was also closely related to ultrafiltration volume.
Endotoxin, IL-6, CRP, and LBP levels were elevated in patients with volume
overload compared to euvolemic patients (p < 0.05). Patients with elevated
circulating endotoxemia had higher left ventricular mass index (LVMI) compared to
patients with lower endotoxin levels. Fluid overload correlated with endotoxin
levels, IL-6, and LVMI; while LVMI correlated weakly with LBP and CRP.
CONCLUSION: CKD patients typically presented with significant endotoxemia and
overt volume overload, which may contribute significantly to chronic low-grade
inflammation and left ventricular dysfunction. An additive contribution from
hemodialysis treatment may strongly enhance the severity of endotoxemia in HD
patients.
PMID- 27509589
TI - The challenges of ESRD care in developing economies: sub-Saharan African
opportunities for significant improvement.
AB - Chronic kidney disease (CKD) is a significant cause of morbidity and mortality in
sub-Saharan Africa. This, along with other noncommunicable diseases like
hypertension, diabetes, and heart diseases, poses a double burden on a region
that is still struggling to cope with the scourge of communicable diseases like
malaria, tuberculosis, HIV, and more recently Ebola. Causes of CKD in the region
are predominantly glomerulonephritis and hypertension, although type 2 diabetes
is also becoming a significant cause as is the retroviral disease. Patients are
generally younger than in the developed world, and there is a significant male
preponderance. Most patients are managed by hemodialysis, with peritoneal
dialysis and kidney transplantation being available in only few countries in the
region. Government funding and support for dialysis is often unavailable, and
when available, often with restrictions. There is a dearth of trained manpower to
treat the disease, and many countries have a limited number of units, which are
often ill-equipped to deal adequately with the number of patients who require end
stage renal disease (ESRD) care in the region. Although there has been a
significant improvement when compared with the situation, even as recently as 10
years ago, there is also the potential for further improvement, which would
significantly improve the outcomes in patients with ESRD in the region. The
information in this review was obtained from a combination of renal registry
reports (published and unpublished), published articles, responses to a
questionnaire sent to nephrologists prior to the World Congress of Nephrology
(WCN) in Cape Town, and from nephrologists attending the WCN in Cape Town (March
13 - 17, 2015).
PMID- 27509590
TI - Peritoneal dialysis treatment of metformin-associated lactic acidosis in a
diabetic nephropathy patient?.
AB - We report a case of metformin-associated lactic acidosis (MALA) in a 66-year-old
man with end-stage renal disease on peritoneal dialysis (PD). The patient
presented with severe lactic acidosis and was treated successfully with automated
peritoneal dialysis (APD). During the treatment, PD solution was prepared from
hemofiltration substitute fluid. The prescription was 8 cycles of 2,000 mL over
24 hours with the prepared solution, and venoclysis with sodium bicarbonate to
improve the acidosis. After 3 days of treatment, his lactic acidosis was
corrected. This case demonstrated that PD using hemofiltration substitute fluid
is an option for patients with MALA.?.
PMID- 27509591
TI - Encapsulated platelets modulate kupffer cell activation and reduce oxidative
stress in a model of acute liver failure.
AB - Acute liver failure (ALF) is characterized by massive hepatocyte cell death.
Kupffer cells (KC) are the first cells to be activated after liver injury. They
secrete cytokines and produce reactive oxygen species, leading to apoptosis of
hepatocytes. In a previous study, we showed that encapsulated platelets (PLTs)
increase survival in a model of ALF. Here, we investigate how PLTs exert their
beneficial effect. Wistar rats submitted to 90% hepatectomy were treated with
PLTs encapsulated in sodium alginate or empty capsules. Animals were euthanized
at 6, 12, 24, 48, and 72 hours after hepatectomy, and livers were collected to
assess oxidative stress, caspase activity, and gene expression related to
oxidative stress or liver function. The number of KCs in the remnant liver was
evaluated. Interaction of encapsulated PLTs and KCs was investigated using a
coculture system. PLTs increase superoxide dismutase and catalase activity and
reduce lipid peroxidation. In addition, caspase 3 activity was reduced in animals
receiving encapsulated PLTs at 48 and 72 hours. Gene expression of endothelial
nitric oxide synthase and nuclear factor kappa B were elevated in the PLT group
at each time point analyzed. Gene expression of albumin and factor V also
increased in the PLT group. The number of KCs in the PLT group returned to normal
levels at 12 hours but remained elevated in the control group until 72 hours.
Finally, PLTs modulate interleukin (IL) 6 and IL10 expression in KCs after 24
hours of coculture. In conclusion, these results indicate that PLTs interact with
KCs in this model and exert their beneficial effect through reduction of
oxidative stress that results in healthier hepatocytes and decreased apoptosis.
Liver Transplantation 22 1562-1572 2016 AASLD.
PMID- 27509592
TI - Insular gliomas and the role of intraoperative assistive technologies: Results
from a volumetry-based retrospective cohort.
AB - INTRODUCTION: In the field of Glioma surgery, there has been an increasing
interest in the use of assistive technologies to overcome the difficulty of
preserving brain function while improving surgical radicality. In most reports,
tumor localization has seldom been considered a variable and the role of
intraoperative adjuncts is yet to be determined for gliomas of the insula.
OBJECTIVES: To evaluate the efficacy of fluorescence-guided resection with 5-ALA,
intraoperative neurophysiological monitoring (IOM), neuronavigation, and
tractography in the Extent of Resection (EOR), functionality scores, overall
survival (OS) and progression-free survival (PFS) in a retrospective cohort of
insular gliomas. METHODS: We reviewed all cases of insular tumors operated on at
the Department of Neurosurgery, University Hospital of Tubingen - Germany,
between May 2008 and November 2013. EOR was determined by volumetric analysis.
Mann Whitney, Chi-square and Kaplan Meier functions were used for assessment of
each technology's effect on primary and secondary outcomes. RESULTS: 28 cases (18
men (64%) and 10 women (36%); median age at diagnosis: 52.5 years, range 12 - 59)
were considered eligible for analysis. High grade and low grade gliomas accounted
for 20 (71%) and 8 (29%) cases, respectively. The most used technologies were IOM
(64%) and Neuronavigation (68%). 5-ALA was the only technique associated with EOR
>=90% (p=0.05). Tractography determined improvement in the Karnofsky Performance
Scale (50% vs. 5% cases improved, p=0.02). There was a positive association
between the use of neuronavigation and overall survival (23 vs. 27.4 months,
p=0.03), but the use of 5-ALA was associated with shorter OS (34.8 vs. 21.1
months, p=0.01) and PFS (24.4 vs. 11.8, p=0.01). CONCLUSIONS: We demonstrate for
the first time that for insular gliomas 5-ALA plays a role in achieving higher
EOR, although this technology was associated with poor OS and PFS; also
tractography and neuronavigation can be of great importance in the treatment of
insular gliomas as they determined better functionality and OS in this study,
respectively. Prospective studies with a more prominent sample and proper
multivariate analysis will help determine the real benefit of these adjuncts in
the setting of insular gliomas.
PMID- 27509593
TI - Free radicals and antioxidant enzymes in older adults after regular senior
elastic band exercising: an experimental randomized controlled pilot study.
AB - AIM: The aim of this study was to pilot test the effects of regular senior
elastic band exercises on the generation of free radicals and antioxidant enzyme
activities in older adults. BACKGROUND: Long-term regular exercises have positive
health promotion outcomes. On the contrary, high-intensity, high-speed and short
term exercises in older adults may increase free radicals and cause chronic
disease and ageing effect. DESIGN: A prospective randomized controlled pilot
study. METHODS: Data were collected during 2012. Twenty-five older adults were
recruited from a community care centre, southern Taiwan and were randomly
assigned to either an experimental or control group. Twenty-two participants
completed the study: experimental group (n = 10) and control group (n = 12). The
experimental group performed 6-month senior elastic band exercises while the
control group kept regular daily routines. Both groups received blood tests
(thiobarbituric acid-reacting substances and glutathione peroxidase) 30 minutes
before the study began and 1 hour after the final intervention treatment.
RESULTS: At the end of the 6-month senior elastic band exercises, no
statistically significant differences in thiobarbituric acid-reacting substances
and glutathione peroxidase values between the experimental and control groups. No
significant differences existed in both thiobarbituric acid-reacting substances
and glutathione peroxidase values before and after the 6-month senior elastic
band exercises either. CONCLUSIONS: Regular senior elastic band exercises did not
increase the generation of free radicals and antioxidant enzyme activities.
Senior elastic band exercises have the potential to be promoted among older
adults in the community as an exercise option without adverse effects on free
radicals and have potential for mitigating ageing and increasing disease control.
PMID- 27509594
TI - Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation
dosimetry and microPET imaging studies of [(18)F]fluorocholine in mice.
AB - [(18)F]Fluorocholine ([(18)F]FCH) has been proven to be effective in prostate
cancer. Since [(18)F]FCH is classified as a new radiopharmaceutical in Brazil,
preclinical safety and efficacy data are required to support clinical trials and
to obtain its approval. The aim of this work was to perform acute toxicity,
biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging
studies of [(18)F]FCH. The results could support its use in nuclear medicine as
an important piece of work for regulatory in Brazil.
PMID- 27509595
TI - Retention of barium and europium radionuclides from aqueous solutions on ash
based sorbents by application of radiochemical techniques.
AB - New materials were synthesized for application in sorption of radionuclides from
aqueous solutions. The elaboration was performed by conversion of power plant ash
using the hydrothermal method under optimum experimental conditions. Sodalite, Na
Y, and analcime were formed from ash precursor during the treatment, exhibiting
thermal stability as revealed by the characterization by X-ray diffraction (XRD)
and thermogravimetric differential thermal analysis (TG-DTA). The Brunauer-Emmett
Teller (BET) surface area and pore volume were determined and they presented
higher values than plant ash. The ability of the new products to retain Ba and Eu
radionuclides was studied in aqueous solutions using (133)Ba and (152)Eu as
tracers and gamma-ray spectroscopy under batch experiments. The experimental data
were modeled by the Langmuir and Freundlich equations, whereas sorption kinetics
measurements were performed at 293, 308, and 323K and thermodynamic parameters
were calculated. The release of the sorbed ions into the environment was also
tested by leaching experiments. The results of these tests indicated that the
synthesized materials are very efficient in removing the aforementioned metals
from aqueous solutions and can be considered as potential low-cost sorbents in
nuclear waste management.
PMID- 27509596
TI - Palliative Care Congress abstracts.
PMID- 27509597
TI - Evaluation of certain veterinary drug residues in food. Eighty-first report of
the Joint FAO/WHO Expert Committee on Food Additives.
AB - This report represents the conclusions of a Joint FAO/WHO Expert Committee
convened to evaluate the safety of residues of certain veterinary drugs in food
and to recommend maximum levels for such residues in food. The first part of the
report considers general principles regarding the evaluation of residues of
veterinary drugs within the terms of reference of the Joint FAO/WHO Expert
Committee on Food Additives (JECFA), including MRLs for generic fish species,
acute reference doses (ARfDs) for veterinary drugs, an approach for dietary
exposure assessment of compounds used for multiple purposes (i.e veterinary drugs
and pesticides), dietary exposure assessment for less-than-lifetime exposure, and
the assessment of short-term (90-day and 12-month) studies in dogs. Summaries
follow of the Committee's evaluations of toxicological and residue data on a
variety of veterinary drugs: two insecticides (diflubenzuron and teflubenzuron),
an antiparasitic agent (ivermectin), an ectoparasiticide (sisapronil) and a beta2
adrenoceptor agonist (zilpaterol hydrochloride). In addition, the Committee
considered issues raised in concern forms from the Codex Committee on Residues of
Veterinary Drugs in Foods on lasalocid sodium, an antiparasitic agent. Annexed to
the report is a summary of the Committee's recommendations on these drugs,
including acceptable daily intakes (ADIs), ARfDs and proposed MRLs.
PMID- 27509598
TI - [Discussion on the impact of acupuncture for the pregnancy of in vitro
fertilization-embryo transfer].
AB - The impact of acupuncture for the pregnancy of in vitro fertilization-embryo
transfer (IVF-ET) is discussed in the paper. Nowadays there are various
conclusions about the impact of acupuncture for IVF-ET, and it may result from
the differences in research designs. The effect is closely related to the
demographic and clinical characteristics of subjects, such as age, the diagnosis
of barrenness, blood flow index of uterine spiral arteries, the cycle of IVF,
etc. Besides, the efficacy is influenced by treatment based on syndrome
differentiation or not, the frequency and course of acupuncture in both the
treating group and the control group, etc. If more reasonable design is achieved
in the further study based on them, more reliable evidence will be provided for
the effect and mechanism of the pregnancy of IVF-EF by acupuncture.
PMID- 27509599
TI - [Acupoints selection based on "disease-symptom-location" combination and
acupuncture treatment of pattern/syndrome differentiation].
AB - The pattern/symptom differentiation system in acupuncture treatment is lack of
the unique characteristics and advantages in theory and clinical practice and it
just rigidly adopts the methods of pattern/symptom differentiation of the other
disciplines in TCM. In fact, it is necessary to have the unique and more
practical theoretic system to guide acupuncture treatment. According to the
characteristics of acupuncture in diagnosis and treatment, the acupoints
selection based on "disease-symptom-location" combination becomes the law of
acupuncture treatment. The acupoints selection based on "disease-symptom
location" combination is the expression to concretize the diagnosis and treatment
of disease under the guidance of pattern/syndrome differentiation. Both of them
are originated from the general principles of TCM and for the particular
disciplines of TCM. The acupoints selection based on "disease-symptom-location"
combination benefits the promotion and application of acupuncture.
PMID- 27509600
TI - [Acupuncture method of "Huoxue Sanfeng, Shugan Jianpi" for morning blood pressure
in patients with cerebral infraction combined with essential hypertension: a
randomized controlled trial].
AB - OBJECTIVE: To observe the clinical effects of acupuncture method of "Huoxue
Sanfeng, Shugan Jianpi" (activating blood and eliminating wind, soothing liver
and strengthening spleen) on morning blood pressure in patients with cerebral
infraction combined with essential hypertension. METHODS: Sixty-eight patients
were randomly divided into an observation group and a control group, 34 cases in
each one. The patients in the two groups were treated with acupuncture method of
"Xingnao Kaiqiao" (consciousness-restoring resuscitation) and oral administration
of nifedipine. In addition, patients in the observation group were treated with
acupuncture method of "Huoxue Sanfeng, Shugan Jianpi" that met the criteria of
standard manipulation, in which bilateral Renying (ST 9), Quchi (LI 11), Hegu (LI
4), Zusanli (ST 36) and Taichong (LR 3) were selected. The treatment was given
once a day, five times a week, for totally six weeks. The improvement and control
rate of morning blood pressure in the two groups were observed. RESULTS: (1)
After treatment, the morning blood pressures were decreased significantly in the
two groups (all P < 0.05); after 15 treatments, the reduction of systolic
pressure and diastolic pressure in the observation group was superior to that in
the control group, but the difference was not significant (both P > 0.05); after
30 treatments, the reduction of systolic pressure and diastolic pressure in the
observation group was significantly superior to that in the control group (both P
< 0.05). (2) After 30 treatments, the control rate of morning blood pressure in
the observation group was significantly higher than that in the control group
[82.4% (28/34) vs 58.8% (20/34), P < 0.05]. CONCLUSION: Acupuncture method of
"Huoxue Sanfeng, Shugan Jianpi", characterized with standard manipulation
criteria, can effectively control morning blood pressure in patients with
cerebral infraction combined with essential hypertension.
PMID- 27509601
TI - [Warming-needle moxibustion for cervical headache: a randomized controlled
trial].
AB - OBJECTIVE: To evaluate the clinical efficacy of warming-needle moxibustion on
cervical headache. METHODS: Sixty-one patients of cervical headache were randomly
divided into a warming-needle moxibustion group (30 cases) and an acupuncture
group (31 cases). Tianzhu (BL 10), Fengchi (GB 20), Wangu (GB 12), Tianyou (TE
16), Hegu (LI 4), Taichong (LR 3) and Zulinqi (GB 41) were selected in the two
groups. Patients in the acupuncture group were treated with acupuncture; patients
in the warming-needle moxibustion group were treated with warming-needle
moxibustion at Tianzhu (BL 10), Fengchi (GB 20) and Wangu (GB 12) and acupuncture
at the remaining acupoints. The treatment was given once every other day, 3 times
a week, and totally 4-week treatment was given. The duration and frequency of
headache, numerical rating scale (NRS) of headache and cervical range of motion
(ROM) were compared before and after treatment in the two groups; also the
efficacy of the two groups was evaluated. RESULTS: After treatment, the duration
and frequency of headache, headache NRS.and cervical ROM score were improved in
both groups (all P < 0.05), which were more significant in the warming-needle
moxibustion group (all P < 0.05). The total effective rate was 84.3% (25/30) in
the warming-needle moxibustion group, which was significantly superior to 61.3%
(19/31) in the acupuncture group (P < 0.05). CONCLUSION: The warming-needle
moxibustion presents significant efficacy on cervical headache, which can
obviously improve headache symptoms and cervical ROM.
PMID- 27509602
TI - [Clinical efficacy comparison between electroacupuncture and meloxicam in the
treatment of knee os- teoarthritis at the early and middle stage: a randomized
controlled trial].
AB - OBJECTIVE: To compare the clinical efficacy on knee osteoarthritis (KOA) at the
early and middle stage between electroacupuncture (EA) and meloxicam. METHODS:
Ninety patients of KOA at the early and middle stage were randomized into an EA
group and a meloxicam group, 45 cases in each one. In the EA group, EA was
applied to Dubi (ST 35), Neixiyan (EX-LE 4), Liangqiu (ST 34), Heding (EX-LE 2),
Xuehai (SP 10), Yan- glingquan (GB 34) and Zusanli (ST 36); the needles were
retained for 20 min and EA was applied once every two days. In the meloxicam
group, the meloxicam tablets were prescribed for oral administration, 7. 5 mg,
once a day. The treatment lasted for 6 weeks in the two groups. The Western
Ontario and McMaster University Osteoarthritis Index (WOMAC) score, rectus
femoris muscle tension, the 8-foot walking test and 5-time sit-to-stand test were
adopted to observe and compare the effects in the two groups. RESULTS: After
treatment, every item score in WOMAC was reduced after treatment (all P < 0.05),
but the difference was not significant between the two groups (all P > 0.05). In
the EA group, the rectus femoris tension after treatment was reduced as compared
with that before treatment (P < 0.05) and the reducing result was much more
apparent as compared with that in the meloxicam group (P < 0.05). For the 8-foot
walking test and 5-time sit-to-stand test, the time was shortened after treatment
in the two groups (all P < 0.05) and the result in the EA group was much more
obvious than that in the meloxicam group (both P < 0.05). CONCLUSION: Both EA and
meloxicam are effective in the treatment of KOA at the early and middle stage. EA
improves rectus femoris tension and recovers the internal mechanics balance and
the efficacy is better than that of meloxicam.
PMID- 27509603
TI - [Clinical efficacy of multi-pattern detumescence after total knee arthroplasty
treated with acupoint massage and mild moxibustion].
AB - OBJECTIVE: To discuss the clinical effect on swelling and pain after total knee
arthroplasty treated with acupoint massage, mild moxibustion and routine
detumescence. METHODS: One hundred and twenty patients of knee osteoarthritis
(KOA) after total knee arthroplasty (TKA), were randomized into an observation
group and a control group, 60 cases in each one. In the control group, after TKA,
the routine detumescence was applied, including elastic bandage compression, the
operated limb raising exercise, knee joint braking, local ice compress,
intermittent pneumatic compression, active ankle pumping and quadriceps
contraction exercise, continuous passive mechanical exercise, using stretch
socks, oral administration of rivaroxaban tablets, 10 mg, once a day,
continuously for 21 to 24 days. In the observation group, on the basis of the
routine detumescence as the control group, 1 h after operation, acupoint massage
was done at Zusanli (ST 36) and Sanyinjiao (SP 6) till soreness and distension
presented, twice a day; 48 h after operation, mild moxibustion was intervened at
Zusanli (ST 36) and Sanyinjiao (SP 6), avoiding burning pain, once a day,
continuously till the 7th day after operation. Before and after operation, the
limb swelling condition and the scores of visual analogue scale (VAS) and HSS
(hospital for special surgery) knee joint function were observed in the patients
of the two groups. RESULTS: On the 1st, 3rd, 5th, 7th and 14th days after
operation, the swelling incidence in the observation group was apparently lower
than that in the control group (P < 0.05, P < 0.01). On the 1st, 3rd, 5th and 7th
days after operation, the scores of VAS in the observation group were lower than
those in the control group (all P < 0.05). On the 7th and 14th days after
operation, the scores of HSS in the observation group were better than those in
the control group (all P < 0.05). CONCLUSION: The combined intervention of
acupoint massage and mild moxibustion reduces the incidence of lower limb
swelling, alleviates pain and promotes knee joint function recovery of TKA and
the effects are better than those achieved by the simple routine detumescence
therapy.
PMID- 27509604
TI - [Case of neck-originated abnormal sensation of throat].
PMID- 27509605
TI - [Effects of acupuncture at stellate ganglion on lower limb atherosclerosis of
early diabetes mellitus].
AB - OBJECTIVE: To compare the efficacy between acupuncture at stellate ganglion
combined with intravenous administration of alprostadil and simple intravenous
administration of alprostadil on lower limb atherosclerosis of early diabetes
mellitus. METHODS: Sixty patients of lower limb atherosclerosis of early diabetes
mellitus were randomly divided into an observation group and a control group, 30
cases in each one. Patients in the two groups were treated with basic treatment
to control blood glucose and lipid. In addition, patients in the control group
were treated with intravenous administration of alprostadil (10 ug) and sodium
chloride solution (100 mL); based on this, patients in the observation group were
treated with acupuncture at stellate ganglion. The treatment was given once a
day; the consecutive treatment of two weeks constituted one session, and totally
4 sessions were given. The total syndrome score, glycosylated hemoglobin (HbA1c),
blood flow of posterior tibial artery and dorsal artery of foot were observed
before and after treatment; the clinical efficacy was compared between the two
groups. RESULTS: Compared before treatment, the total syndrome score, HbA1c,
blood flow of posterior tibial artery and dorsal artery of foot were
significantly improved after treatment (all P < 0.05), which were more obvious in
the observation group (all P < 0.05). After treatment, the total effective rate
was 93.3% (28/30) in the observation group, which was significantly superior to
86.7% (26/30) in the control group (P < 0.05). CONCLUSION Acupuncture at stellate
ganglion combined with intravenous administration of alprostadil achieve better
effect than simple intravenous administration of alprostadil for lower limb
atherosclerosis of early diabetes mellitus, which improve the clinical symptoms,
regulate blood sugar and increase the blood flow of lower limb.
PMID- 27509606
TI - [Acupuncture for distal symmetric multiple peripheral neuropathy of diabetes
mellitus: a randomized controlled trial].
AB - OBJECTIVE: To compare the clinical efficacy between acupuncture and intravenous
administration of lipoic acid and alprostadil for distal symmetric multiple
peripheral neuropathy of diabetes mellitus. METHODS: Sixty patients were randomly
divided into an acupuncture group (31 cases) and a medication group (29 cases).
Patients in the two groups received basic treatment to control blood sugar within
a safe range. On this basis, patients in the acupuncture group were treated with
acupuncture at Geshu (BL 17), Weiwanxiashu (EX-B 3), Ganshu (BL 18), Pishu (BL
20), Shenshu (BL 23), Zusanli (ST 36), Taixi (KI 3), ashi points, etc. Patients
in the medication group were treated with intravenous administration of lipoic
acid (0.6 g) and alprostadil (10 mg). The treatment was given once a day, 10 days
for a course of treatment; there was an interval of 2 days between courses, and
totally 3 courses were given. The score of peripheral neuropathy of diabetes
mellitus, the change of nerve conduction: velocity and clinical efficacy before
and after treatment in the two groups were observed. RESULTS: After treatment,
the score of peripheral neuropathy was significantly reduced in the two groups
(both P < 0.05), which was more significant in the acupuncture group (P < 0.05).
After treatment, the sensory nerve conduction velocity (SNCV) and motor nerve
conduction velocity (MNCV) of median nerve and common peroneal nerve were
significantly increased in the two groups (all P < 0.05). Compared between two
groups, the SNCV and MNCV of common peroneal nerve in the acupuncture group were
significantly superior to those in the medication group (both P < 0.05); the MNCV
of median nerve in the acupuncture group was significantly superior to that in
the medication group (P < 0.05); the SNCV of median nerve in the acupuncture
group was not significantly different from that in the medication group (P >
0.05). The total effective rate was 83.9% (26/31) in the acupuncture group, which
was significantly superior to 62.1% (18/29) in the medication group (P < 0.05).
CONCLUSION: Acupuncture and conventional medication both have satisfied effects
for distal symmetric multiple peripheral neuropathy of diabetes mellitus, and
acupuncture is superior to medication on improving clinical signs of sensory
disorder, reflection disturbance and muscle weakness, nerve conduction and
clinical curative effect.
PMID- 27509607
TI - [TEAS for prevention and treatment of orthodontic toothache and oral dysfunction:
a randomized controlled trial].
AB - OBJECTIVE: To observe the clinical efficacy of transcutanclus electrical acupoint
stimulation (TEAS) on prevention and treatment of orthodontic toothache and oral
dysfunction. METHODS: A total of 85 patients of malocclusions in the preliminary
diagnosis were randomly divided into a control group (20 cases), a psychological
intervention group (22 cases), a medication group (20 cases) and a TEAS group (23
cases). Orthodontics treatment was given in all the groups. Patients in the
control group received no further treatment; patients in the psychological
intervention group received comprehensive psychological intervention, including
cognitive education and music therapy; patients in the medication group received
oral administration of ibuprofen; patients in the TEAS group received TEAS at
Juliao (ST 3), Jiachengjiang (Extra) and auricular point Ya (LO1). The treatment
was given twice a day, one in morning and one at night, for 7 days. The pain
scores of orthodontic toothache and changes of oral dysfunction were observed in
all groups. RESULTS: (1) At 5 time points from the 12th hour to the 4th day, the
scores of spontaneous pain in TEAS group were lower than those in the control
group (all P < 0.01); during the time points, the scores in TEAS group were lower
than those in the psychological intervention group (P < 0.05, P < 0.01), which
were similar to those in the medication group (all P > 0.05). (2) During the peak
cycle of spontaneous toothache, the scores of irritation pain in TEAS group were
significantly lower than those in the control group (all P < O.01), regardless of
time-point statistics or general statistics; the scores of irritation pain in the
TEAS group were also significantly lower than those in the psychological
intervention group (all P < 0.01), which were similar to those in the medication
group (all P > 0. 05). (3) Compared with control group, the grading of talking
disorder in the remaining groups did not change significantly (P > 0.05). (4)
Compared with control group, the grading of moderate-severe eating disorder in
TEAS group was significantly reduced (P < O.05), which was not different from
that in the medication group (P > 0.05). The differences of the grading of
moderate-severe eating disorder were not significantly different between the
psychological intervention group and control group (P > 0.05). (5) There were 3
cases of digestive system adverse reactions in the medication group. CONCLUSION:
TEAS can efficiently prevent orthodontic toothache and oral dysfunction, which is
superior to psychological intervention and similar to medication. In addition, it
can avoid possible side-effect of medication.
PMID- 27509608
TI - [Effect of acupuncture for pain threshold among the groups of different
constitutions].
AB - OBJECTIVE: To observe the difference in acupuncture for pain threshold at
different time points among the groups of 9 TCM constitutions. METHODS: The cross
sectional survey was adopted to investigate TCM constitutions among 600 subjects
and determine 9 TCM constitution types (neutral constitution, qi-deficiency
constitution, yang-deficiency constitution, yin-deficiency constitution, phlegm
damp constitution, damp-heat constitution, blood-stagnation constitution, qi
stagnation constitution, special diathesis constitution). The same acupuncture
manipulation was applied to Zusanli (ST 36) on the left side in the subjects and
the needle was retained for 30 min. The tenderness threshold was detected with
2390 type Von Frey apparatus at different time points, named before acupuncture,
at the moment after qi arrival, in 10 min of needle retaining, in 30 min of
needle retaining and in 15 min after needle withdrawal in the subjects of 9 TCM
constitutions. RESULTS: The interactive effect happened between the constitution
type and time point (P < 0.05). Among the groups of 9 TCM constitutions, the pain
threshold values at the moment after qi arrival (except blood-stagnation
constitution, qi-stagnation constitution, special diathesis constitution) in 10
min of needle retaining and in 30 min of needle retaining were increased as
compared with those before acupuncture separately (P < 0.01), among which, the
value increase was the most significant in 30 min of needle retaining. The
differences in the pain thresholds were significant in 15 min after needle
withdrawal in the groups of neutral constitution and damp-heat constitution as
compared with those before acupuncture (both P < 0.01). In 10 min of needle
retaining and in 30 min of needle retaining, as compared with the group of
neutral constitution, the changes in pain thresholds of the rest abnormal
constitutions were apparently lower (all P < 0.05). CONCLUSION: Acupuncture at
Zusanli (ST 36) presents different effects among the groups of different
constitution types. The effect maintaining durations are different.
PMID- 27509609
TI - [Case of rectal carcinoma postoperative intestinal obstruction].
PMID- 27509610
TI - [Herbal umbilicus therapy plus hot compress with salt packet for 20 cases of
malignant ascites].
PMID- 27509612
TI - [Case of macular degeneration].
PMID- 27509611
TI - [Micronucleus in vitro induced by inhalable particulate matters in moxa smoke].
AB - OBJECTIVE: To investigate whether inhalable particulate matters can cause the
damage of chromosome or mitotic apparatus to produce micronucleus, and to
evaluate genetic toxicology of moxa smoke on chromosome. METHODS: By MTT method,
the 24 h half maximal inhibitory concentration (IC50) of moxa smoke condensation
(MSC) on Chinese hamster ovary (CHO) cells was 0.087 mg/mL. CHO cells, which were
cultured in vitro, were divided into a solvent control group, a positive control
group (cyclophosphamide as solvent), a low concentration group, a moderate
concentration group and a high concentration group. The low concentration group,
moderate concentration group and high concentration group were set approximately
1/8, 1/4, 1/2 of IC50, respectively. Whether micronucleus had dose-effect
response induced by the damage of chromosome or mitotic apparatus was observed
after CHO cells were contaminated by MSC in the low concentration group, moderate
concentration group and high concentration group. RESULTS: The rate of
micronucleus induced by MSC in the low concentration group, moderate
concentration group and high concentration group was higher than that in the
solvent control group (all P < 0.05), which presented dosage-effect response. The
experiment was repeated 3 times, indicating it was repeatable with statistical
significance. CONCLUSION: High concentration of MSC shows toxicity to induce
chromosome damage, which disappears at low concentration. The genetic toxicology
is also dependent on concentration, and the concentration of moxa smoke is
essential. In clinical treatment, it is noted to control the level of moxa smoke,
while the clinical safety standard of moxa smoke concentration is in need of
further study.
PMID- 27509613
TI - [Effects of electroacupuncture pretreatment on ovarian function and expression of
VEGF in rats with ovulation induction].
AB - OBJECTIVE: To explore the protective effect of electroacupuncture (EA)
pretreatment on ovarian function in rats with ovulation induction. METHODS:
Thirty SD female rats were numbered according to random number table. According
to vaginal smear method, rats of estrus were divided into a normal group (10
rats) and cohabitated with male SD rats with the proportion of 1:1. With computer
generated random number, the remaining rats were divided into a model group and
an EA group, 10 rats in each one. The model of superovulation was established
with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin
(HCG) in the model group and EA group. Before model establishment and
cohabitation, rats in the EA group were treated with EA at "Guanyuan (CV 4)" and
"Sanyinjiao (SP 6)", once for 15 min, for consecutive 7 days. Rats in the normal
group and model group received no further treatment. The third day 23:00 pm after
cohabitation, blood samples in three groups were collected to test the level of
estradiol (E2) and progesterone (P). After the rats were sacrificed, the HE
staining method was applied to observe the morphological changes of ovarian
tissue; the immunohistochemical method was applied to measure the expression of
vascular endothelial growth factor (VEGF) and its receptor VEGFR-2; the real-time
quantitative PCR technique was applied to measure the gene expression of VEGF and
VEGFR-2. RESULTS: The number of ovarian follicle in the EA group was higher than
that in the model group and normal group (all P < 0.05); the ratio of corpus
luteum size to ovarian size in the EA group was lower than that in the model
group (P < 0.01). The ratio of plasma estradiol to progesterone in the EA group
tended to be normal group (P < 0.05) and lower than that in the model group (P <
0.01). The protein expression of VEGF and VEGFR-2 in lutein granulosa cell and
follicular fluid in the EA group was lower than that in the model group (P <
0.05); gene level of VEGF and VEGFR-2 in ovarian tissue in the EA group was lower
than that in the model group (P < 0.05, P < 0.01). CONCLUSION: EA pretreatment
has certain protective effect on ovarian function in rats with ovulation
induction, which is likely to be related to regulation of VEGF and its receptor.
PMID- 27509614
TI - [Mechanism of electroacupuncture on "Zusanli (ST 36)" for chemotherapy-induced
peripheral neuropathy].
AB - OBJECTIVE: To observe the effects and duration of electroacupuncture on the
mechanical pain threshold induced by paclitaxel and explore its analgesic
mechanism. METHODS: Sixty-four C57BL/6J male mice were randomly divided into 4
groups, a normal+sham EA group, a normal+EA group, a medicine+sham EA(Med+ sham
EA) group, a medicine + EA (Med + EA) group, 16 cases in each group. The model of
chemotherapy-induced peripheral neuropathy was established with paclitaxel
intraperitoneal injection on the 1st, 3rd, 5th, 7th day in the Med + sham EA
group and the Med + EA group. EA of 30 min was used on bilateral "Zusanli (ST
36)" on the 9th, 11th, 13th, 16th, 18th, 20th, 23rd, 25th, 27th, 30th day in the
EA groups, 2 Hz/100 Hz and 1~ 1.5 mA. Acupuncture was applied on the same
acupoint at the same times in the sham EA groups. Mechanical pain thresholds were
tested by VonFrey before and after model establishment, namely on the 8th, 14th;
21st and, 28th day. The heart blood of 8 mice was drawn quickly to collect serum
in every group on the 31st day, and the contents of tumor necrosis factor alpha
(TNF-alpha), interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta) in
proinflammatory cytokine were examined by ELISA. Mechanical pain thresholds were
tested by VonFrey for the rest 8 mice of each group until there was no apparent
difference in the two paclitaxel groups once a week,namely on the 35th, 42nd,
49th day. RESULTS: The pain thresholds of each group were not statistically
different before model establishment (P > 0.05). After model establishment (on
the 8th day), thresholds of the paclitaxel groups were lower than those of the
normal groups (all P < 0.05). After EA, the mechanical pain thresholds of the Med
+ EA group were higher than those of the Med + sham EA group at all the time
points, and there was statistical difference on the 14th, 21st and 28th day (all
P < 0.05). The analgesic effect was lasting to the 49th day. The contents of TNF
alpha, IL-1alpha, IL-1beta of the Med + EA group were decreased than those of the
Med+sham EA group in different degree, with statistical significance of IL-1alpha
(P < 0.05). CONCLUSION: EA can effectively treat paclitaxel-induced peripheral
neuropathy,and the analgesic mechanism is probably related to decreasing the
proinflammatory cytokine.
PMID- 27509615
TI - [Effects of electrical stimulation at acupoints in the distribution area of
auricular vagus nerve combined with sound masking method on auditory brainstem
response and neurotransmitters of inferior colliculus in rats of tinnitus].
AB - OBJECTIVE: To explore the effects of electrical stimulation at acupoints in the
distribution area of auricular vagus nerve combined with sound masking on
auditory brainstem response (ABR) and contents of neurotransmitters of gamma
aminobutyric acid (gamma-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline
(Ach) in inferior colliculus of tinnitus rats. METHODS: Twenty-four male adult SD
rats were randomized into a control group, a model group, a 7-d treatment group
and a 15-d treatment group. Except the control group, rats in the remaining
groups were treated with intraperitoneal injection of 10% salicylate sodium at a
dose of 350 mg/kg to establish tinnitus model. Rats in the control group were
treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d
treatment group were treated with electrical stimulation at "Shenmen (TF4)" and
"Yidan (CO11)" in the distribution area of auricular vagus nerve combined with
sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT
system was applied to provide voice for single ear and collect the signal, and
the voice threshold of ABR was tested. The levels of gamma-GABA, 5-HT and Ach in
inferior colliculus of rats were detected by enzyme linked immunosorbent assay
(ELISA) and compared. RESULTS: Compared with the model group, the threshold
values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group
were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to
28 kHz voice stimulation in the 15-d treatment group were signally reduced (P <
0.05, P < 0.01), which was more significant than those in the 7-d treatment
group. The level of gamma-GABA in the model group was significantly lower than
that in the control group (P < 0.05), and that in the 15-d treatment group was
apparently higher than that in the model group (P < 0.05). The level of 5-HT in
the model group was markedly higher than that in the control group (P < 0.05),
and that in the 7-d treatment group was lower than that in the model group (P <
0.05), while that in the 15-d treatment group was apparently higher than that in
the model group (P < 0.05). The level of Ach in the model group was obviously;
lower than that in the control group (P < 0.05), and that in the 7-d treatment
group was higher than that in the model group (P < 0.05). CONCLUSION: Electrical
stimulation at auricular vagus nerve combined with sound masking) could regulate
the threshold of ABR, especially in the 15-d treatment group. This may be
ascribed to modulating the levels of neurotransmitter of gamma-GABA, 5-HT and Ach
in inferior colliculus.
PMID- 27509616
TI - [Teaching design of mastering scalp acupuncture fast].
AB - Scalp acupuncture is a method of treating whole-body diseases. The author takes
the easy positioning of scalp acupuncture as starting point, covers the
positioning of scalp acupuncture and needle insertion points, acupuncture
manipulation and the selection of acupoints, so as to introduce the design of
teaching the international standardized scalp acupuncture with texts and
illustrations. The positions of scalp acupuncture are 4 lines in frontal area, 5
lines in parietal area, 2 lines in temporal area and 3 lines in occipital area.
The needle insertion angle is 30 degrees to the skin. Acupoints can be selected
crossly and correspondingly in clinic.
PMID- 27509617
TI - [Case of enuresis after total hysterectomy].
PMID- 27509618
TI - [Case of Hirschsprung's disease allied disorder in child].
PMID- 27509619
TI - ["Chuan Jia Re" combined with abdominal needle for 23 cases of periarthritis of
shoulder with wind cold dampness type].
PMID- 27509620
TI - [Explanation of Evidence-based Guidelines of Clinical Practice with Acupuncture
and Moxibustion: Adult Bronchial Asthma].
AB - The development and compilation of Evidence-based Guidelines of Clinical Practice
with Acupuncture and Moxibustion: Adult Bronchial Asthma are introduced from
three aspects, named the guideline methodology, the guideline structure and the
guideline content. Based on the acupuncture-moxibustion practice and clinical
research, the evidence-based medicine method is adopted. During the development
and compilation of the guideline, the characteristics and advantages of
acupuncture and moxibustion are specially considered in the treatment of this
disease; the latest optimum evidences at home and abroad, experts' experience and
patients' value are closely integrated with each other. Additionally, the
worldwide accepted assessments of evidence quality and the recommendation (GRADE
system) are combined with the clinical evidences of the ancient and modern famous
acupuncture-moxibustion experts, and the clinical research evidences are with the
experts' consensus to the large extent. The purpose of the guideline is to
provide the maximal guidance to the clinical physicians.
PMID- 27509621
TI - [Qijie theory of LAI's Tongyuan acupuncture technique].
AB - Qijie theory is one of the important components of TCM meridian and collateral
system. It is the shortcut for the communication from the exterior to the
interior and for the transverse connection, strengthens the therapeutic effects
of acupuncture and moxibustion on the disorders of internal organs and enlarges
the indications of acupoints. Professor LAI Xinsheng originally creats Tongyuan
acupuncture technique. It is a kind of acupuncture therapeutic methods, including
promoting the circulation of the governor vessel, regulating the mind and
conducting qi to the origin. In order to analyze the connection between Tongyuan
acupuncture technique and traditional meridian and collateral theory, the
connotations of Tongyuan acupuncture technique and qijie, as well as the in
terrelationship between them are taken as the basis in the paper. By tracing the
literature records, the original concept of qijie is detected. Through proving
clinically Tongyuan acupuncture technique, it is revealed that qijie is the
arrowhead on the main road of meridian qi circulation and is the essential
connotation of the direct path of the body surface connecting with the deep
layers of the body as well as the zangfu organs and tissues. It is summarized
that the traditional qijie theory provides the powerful theoretic evidence for
the treatment with Tongyuan acupuncture technique.
PMID- 27509622
TI - [Meaning of exegetics research on acupoint name].
AB - Acupoint name has rich TCM meaning and cultural connotation and its nomenclature
originates from ancient Chinese. In order to clearly explore the significance of
acupoint name, the exegetics is used in this study. It is found that the study on
acupoint name contributed to determining the controversial acupoint locations and
revealing the cultural connotation and the basic TCM theory behind the acupoint.
Additionally, it helps us to understand the effect mechanisms of acupoints
[Tianshu (ST 25) is either for constipation or diarrhea as an example], dig the
clinical effects of acupoints, discover and rectify the mistakes in nomenclatures
such as pronunciation and glyph. All of these study results benefit the accurate
and comprehensive recognition on the acupoints.
PMID- 27509623
TI - [Profound meaning of acupuncture taboos in Internal Classic based on the fault of
reinforcing and reducing technique by mind conduction of acupuncture therapy].
AB - By analyzing the acupuncture taboos in Neijing (Internal Classic) on clinical
application of mind conduction of acupuncture therapy in going against the actual
situation, astronomy and others, it is found that the relevant acupuncture taboo
implies many subtle mysteries of human body, qi, mind and astronomy, which have
not been discovered yet in modern science and are very significant in qi
protection. In Neijing, the acupuncture physicians have been highly required in
the mind treatment, in which, accurately regulating qi circulation is the target
in the treatment. The mind conduction is used for qi circulation to accomplish
accurately the reinforcing or reducing in the deficiency or excess condition. All
of the taboos are provided to normalize the accuracy of reinforcing and reducing
technique of acupuncture therapy and avoid the damage of qi in human body. Hence,
those taboos must be obeyed so as to prevent from serious consequence and ensure
the safety of this acupuncture therapy.
PMID- 27509624
TI - [Case of multiple system atrophy].
PMID- 27509625
TI - [Analysis on intestinal disorders in Jiujing Tu (Illustration of Moxiustion)
found from Dunhuang].
AB - Jiujing Tu (Illustration of Moxibustion), excavated from Mo Kao Grotto at
Dunhuang, is one of the earliest existing monographs on moxibustion. The medical
masters from different schools have focused on this book because it is different
from the existing ancient medical works and have not been collected in the
medical works of different dynasties. In this study, the literature of Jiujing Tu
on five acupoints (Dachangshu, Pangguangshu, Daxiaochangshu, Nieshu and Cigong)
relevant with intestinal disorders is collected. It is intended to discuss and
analyze the acupoint location, main intestinal disorder, moxibustion characters,
recognition on the literature of different dynasties and modern clinical
applications. It is believed that the thought of strong moxibustion in the
treatment of intestinal disorders advocated in Jiujing Tu has profound impact on
the medical development in later generations. It deserves us to have a further
digging, collection and promotion of this thought in the modern time.
PMID- 27509626
TI - [On the partition of acupuncture academic schools].
AB - Nowadays extensive attention has been paid on the research of acupuncture
academic schools, however, a widely accepted method of partition of acupuncture
academic schools is still in need. In this paper, the methods of partition of
acupuncture academic schools in the history have been arranged, and three typical
methods of"partition of five schools" "partition of eighteen schools" and "two
stage based partition" are summarized. After adeep analysis on the disadvantages
and advantages of these three methods, a new method of partition of acupuncture
academic schools that is called "three-stage based partition" is proposed. In
this method, after the overall acupuncture academic schools are divided into an
ancient stage, a modern stage and a contemporary stage, each schoolis divided
into its sub-school category. It is believed that this method of partition can
remedy the weaknesses ofcurrent methods, but also explore a new model of
inheritance and development under a different aspect through thedifferentiation
and interaction of acupuncture academic schools at three stages.
PMID- 27509627
TI - [Present situation and development direction of microacupuncture therapy].
AB - There have been many reports of clinical and experimental researches of
microacupuncture therapy, the relevant systematic works, teaching materials and
national standards in recent decades. It shows that microacupuncture system has
been formed and its influence has been promoted. While the rapid development of
microacupuncture therapy, there are the problems and contradictions on
nomenclature, explanation of theoretical basis, optimal indications, and multiple
systems and schools, etc. All the above have blocked the clinical application and
development. It is considered that we need to unify the nomenclature, condense
the theoretical basis, clear the optimal indications, promote the exchange and
blend among different schools and sum up the outcomes by systematic review and
data mining technique.
PMID- 27509628
TI - [Case of epilepsy after cerebral hemorrhage caused by traumatism].
PMID- 27509629
TI - Overseeing Compliance.
AB - Boards can take six practical and simple steps to avoid claims of personal
liability.
PMID- 27509630
TI - Rural Trustees Take on the World.
AB - The dramatic changes underway in health care today have tremendous implications
for rural hospitals, and board members must work continuously to understand and
react to them.
PMID- 27509631
TI - For Rural Boards, an Imperative to Change.
AB - Integrated governance, megaboards and "coopetition" are among the op-tions
trustees might consider in an increasingly complex health care field Here are
seven questions they can ask now.
PMID- 27509632
TI - Success Against Sepsis.
AB - Sepsis remains one of the most vexing and persistent health care-associated
conditions. But hospitals are refusing to back down. Here are strategies they're
using to step up the battle.
PMID- 27509633
TI - Adaptability in the Face of Uncertainty.
PMID- 27509634
TI - Women in Governance: A Savvy Strategy for Advancing Community Health.
AB - Women in governance: A savvy strategy for advancing community health.
PMID- 27509635
TI - Taming the Roller Coaster.
AB - The Rural Health Care Leadership Conference offers the chance for executives and
board members to network and gain insights from each other and expert presenters.
And there's a bonus: It's in Phoenix in February.
PMID- 27509636
TI - The Board Chair's Journey.
AB - A real-world rumination on the journey of a hospital board chair and five things
that will make it sucessful, from someone who knows.
PMID- 27509637
TI - Asking Incisive Questions.
AB - Boards must help management chal- lenge their deeply held beliefs about health
care by asking incisive questions.
PMID- 27509638
TI - The Opioid Crisis and the Physician's Role in Contributing to its Resolution:
Step One--Prevention of Overdoses.
AB - The escalation of opioid prescriptions, associated misuse, and related mortality
continues to pose public health challenges in the United States. Data from the
Centers for Disease Control and Prevention (CDC) indicates that opioid overdose
death rates remain high, suggesting the need for improved access to, and use of
naloxone to save lives. In this context, community-based overdose initiatives
have trained laypersons to identify overdose and administer naloxone for
reversal. Although there have been efforts to encourage physicians to prescribe
naloxone to patients at-risk for opioid overdose, the rate of prescribing remains
suboptimal. This article outlines the epidemiology of overdoses, discusses
naloxone distribution programs and myths surrounding its use, and reviews
relevant legislative developments in Connecticut and proper counseling of
patients and families to encourage broader education and prescribing of naloxone.
PMID- 27509639
TI - Does Initial Imaging Modality Affect Breast Biopsy Upgrade Rates? A Single
Institution Review.
AB - INTRODUCTION: Image-guided core needle biopsy (CNB) is the standard for
diagnostic breast biopsy. However, the upgrade rate to a higher order lesion
defined as identification of malignancy on final pathology from surgical excision
remains problematic. MATERIALS AND METHODS: A retrospective chart review of all
core needle biopsies from 2008 to 2012 was performed. We identified lesions
demonstrating atypia without associated malignancy on core needle biopsy and
recorded multiple factors to evaluate predictors of upgrade. RESULTS: Of 151
independent core needle biopsies recorded, 26.5% were upgraded to a higher order
lesion. Concurrent mammogram and ultrasound (US) were associated with higher
sampling error than any individual imaging modality (P = .021). MRI had a trend
toward lower rate of upgrade rate but did not reach statistical significance.
DISCUSSION: Although MRI had a lower rate of upgrade rate due to sampling error,
this did not reach significance possibly because of our small sample size.
PMID- 27509640
TI - Ceramic-on-Ceramic Total Hip Arthroplasty in a Twelve-Year-Old Patient: Case
Report with a 27-Year Follow-Up.
AB - Total hip arthroplasty in the juvenile patient with a severely diseasedjoint can
provide long-term pain relief and improvement in function. We present a patient
with juvenile rheumatoid arthritis who underwent a Mittelmeier ceramic-on-ceramic
total hip arthroplasty at age 12 in 1986. The implant provided the patient with a
functioning hip for 24 years, but subsequently required revision due to femoral
component loosening. This case report represents the longest reported clinical
follow-up of noncemented, ceramic-on-ceramic total hip arthroplasty in a juvenile
patient and depicts an excellent outcome at 27 years. Our case is also unique in
that the Mittelmeier ceramic acetabulum was left in place during revision
surgery. In this report, we also describe the senior author's choice of the
Mittelmeier hip prosthesis within its historical context and provide a brief
review of the literature as it relates to total hip arthroplasty in the juvenile
patient.
PMID- 27509641
TI - Adenovirus Pneumonia Mimicking Legionnaire's Disease with Acute Pancreatitis.
PMID- 27509642
TI - Primary Myeloid Sarcoma of the Small Intestine: Case Report and Literature
Review.
AB - Primary myeloid sarcoma is a rare extramedullary manifestation of acute myeloid
leukemia (AML). Typically, myeloid sarcoma presents after a diagnosis of AML or
other myeloproliferative disorder. However, primary myeloid sarcoma may present
without any preexisting condition, thereby making it extremely difficult to
diagnose. We discuss a case of a 22-year-old female who was misdiagnosed
initially with acute appendicitis and underwent an appendectomy. Postoperatively,
she continued to be symptomatic and eventually developed small bowel obstruction.
Diagnostic laparoscopy revealed multiple small bowel masses as well as diffuse
abdominal and pelvic lymphadenopathy. After extensive pathological review and
additional workup consisting of immunohistochemistry and molecular studies, the
correct diagnosis of myeloid sarcoma was made. This review will discuss the
presentation, diagnosis, management, and prognosis of primary myeloid sarcoma.
PMID- 27509643
TI - Rapidly Fatal Dissemination of Merkel Cell Carcinoma in a Patient Treated with
Alemtuzumab for Chronic Lymphocytic Leukemia.
AB - Alemtuzumab is FDA-approved for the treatment of chronic lymphocytic leukemia
(CLL). Nonetheless, its use for this indication has fallen out of favor due to
serious concerns for infectious complications and increased risks of second
malignancies from the profound and lasting immunosuppression. We report here in a
patient with a rapidly progressive metastatic Merkel cell carcinoma (MCC) who was
previously treated with alemtuzumab and fludarabine for CLL. He developed
profound lymphopenia and hypogammaglobulinemia. While the risk of MCC is
increased in CLL, its rapid dissemination has not been previously reported with
fludarabine alone. In light of the rapidly fatal outcome in our patient due to
MCC, we advise caution with the use of alemtuzumab. In patients treated with
alemtuzumab for nononcologic indications, aggressive surveillance for cutaneous
malignancies should be implemented until its safety profile can be further
characterized.
PMID- 27509644
TI - The Respimat Soft Mist Inhaler, a Novel Inhaled Drug Delivery Device.
AB - Summary The Respimat SMI offers a novel delivery mechanism for the management of
primarily COPD, but asthma as well. Presently, four different medications, as
monotherapy or a combination of two active ingredients, are available using the
Respimat SMI technology. Multiple studies have demonstrated safety and efficacy
of these drugs when delivered via Respimat SMI. Patients tend to prefer the
Respimat SMI over traditional inhaler devices, as it overcomes some of the
disadvantages posed by traditional delivery devices.
PMID- 27509645
TI - Spiro Writing Awards 2016.
PMID- 27509646
TI - The Destruction of Clinical Medicine and What is Needed for its Resurrection.
PMID- 27509647
TI - CDC Opioid Guidelines in Today's Drug Culture.
PMID- 27509648
TI - Spring Update.
PMID- 27509649
TI - Climbing Steep Hills.
PMID- 27509650
TI - [ANTITHROMBOTIC MEDICATION IN PREGNANT WOMEN WITH PREVIOUS INTRAUTERINE GROWTH
RESTRICTION].
AB - AIM: To analyze pregnancy outcome in patients who were on antithrombotic
medication (AM) because of previous pregnancy with fetal intrauterine growth
restriction (IUGR). MATERIALS AND METHODS: The studied group (SG) included 21
pregnancies in 15 women with history of previous IUGR. The patients were on low
dose aspirin (LDA) and/or low molecular weight heparin (LMWH). Pregnancy outcome
was compared to the one in two more groups: 1) primary group (PG) including the
previous 15 pregnancies with IUGR of the same women; 2) control group (CG)
including 45 pregnancies of women matched for parity with the ones in the SG,
with no history of IUGR and without medication. The SG, PG and CG were compared
for the following: mean gestational age (g.a.) at birth, mean birth weight (BW),
proportion of cases with early preeclampsia (PE), IUGR (total, moderate, and
severe), intrauterine fetal death (IUFD), neonatal death (NND), admission to
NICU, cesarean section (CS) because of chronic or acute fetal distress (FD)
related to IUGR, PE or placental abruption. Student's t-test was applied to
assess differences between the groups. P values < 0.05 were considered
statistically significant. RESULTS: The differences between the SG and the PG
regarding mean g. a. at delivery (33.7 and 29.8 w.g. respectively) and the
proportion of babies admitted to NICU (66.7% vs. 71.4%) were not statistically
significant. The mean BW in the SG (2114,7 g.) was significantly higher than in
the PG (1090.8 g.). In the SG compared with the PG there were significantly less
cases of IUFD (14.3% and 53.3% respectively), early PE (9.5% vs. 46.7%) moderate
and severe IUGR (10.5% and 36.8% vs. 41.7% and 58.3%). Neonatal mortality in the
SG (5.6%) was significantly lower than in the PG (57.1%), The proportion of CS
for FD was not significantly different--53.3% in the SG and 57.1% in the PG. On
the other hand, comparison between the SG and the CG demonstrated significantly
lower g.a. at delivery in the SG (33.7 vs. 38 w.g.) an lower BW (2114 vs. 3094
g). There were significantly more cases with IUGR in the SG compared to the CG-
total, moderate and severe (47.4 %, 10.5% and 36.8% in the SG vs. 8.9%, 6.7% and
2.2% in the CG) and NICU admissions (66.7% vs. 4.4%). There were no cases in the
control group with severe PE (9.5% in the SG), IUFD (14.3% in the SG), and CS for
FD (53.3% in the SG). The proportion of pregnancies without complication in the
SG (23.8%) was significantly lower than in the CG (86.7%). CONCLUSIONS: The
outcome of pregnancies with AM because of previous fetal IUGR is improved
compared to the index ones. However, it is less favorable compared to the outcome
in matched cases with no history of IUGR in previous pregnancies.
PMID- 27509651
TI - [CLINICAL IMPLEMENTATION OF CELL-FREE DNA ANALYSIS IN MATERNAL BLOOD IN SCREENING
FOR ANEUPLOIDIES IN SINGLETON PREGNANCIES].
AB - OBJECTIVE: Clinical implementation of cell free(cf) DNA testing in maternal blood
for aneuploidies in singleton pregnancies. METHODS: This is a retrospective study
conducted in two centers for fetal medicine in Sofia, Bulgaria, between October
2013 and August 2015. We examined the clinical implementation of cf DNA testing
in the routine practice for trisomies 21, 18 and13 after the performance of the
first trimester combined test, second trimester biochemical test and/or the
combination between first and second trimester integrated test. RESULTS: Cell
free DNA testing was performed in 170 singleton pregnancies with a median
maternal age of 35 (range 22-46) years. The primary risk assessment for
aneuploidies was derived from 95 cases after the first trimester combined
screening test, 39 cases after the second trimester biochemical screening test,
16 cases after the integrated screening test and 20 cases there were no screening
test performed. The results from the first line screening test were : 8
pregnancies with risk for trisomy 21 > 1: 100; 23 pregnancies with risk for
trisomy 21 from 1:100 to 1: 300; 43 pregnancies with risk for trisomy 21 from
1:300 to 1:1000 and 76 pregnancies with risk for trisomy 21 < 1: 1000. No
pregnancies with high risk for T13/T18 were identified. The analysis of cf DNA in
the maternal blood reported 3 cases with T21 and no cases with T18 or T13. There
was only one case of T21 in the group with risk >1:100 identified by the cf DNA
analysis which was also identified by the first trimester combined screening
test. The positive results were confirmed with invasive testing: CVS in the first
trimester (one case) and Amniocentesis in the second trimester (two cases).
CONCLUSION: Clinical implementation of cell-free DNA analysis in the contingent
policy for screening could improve the detection rate for T21 and could reduce
the rate of invasive procedures.
PMID- 27509652
TI - [HYPERTENSIVE DISORDERS IN PREGNANT WOMAN WITH EPILEPSY].
AB - PURPOSE: To determine the frequency and the course of hypertensive disorders in
pregnant women with epilepsy (PWWE). MATERIALS AND METHODS: The survey is
prospective and covers 206 PWWE during the period 1997-2012 year, monitored and
treated in Risk Pregnancy Clinic of University Hospital - Pleven. All the
patients (PWWE) are with clinically established etiology and prescription of
epilepsy, type of seizures and their frequency. EEG records, ultrasound of fetus
and cardiotocograph monitoring were conducted. Eleven of PWWE were with
Praeeclampsia - Eclampsia (PE-Ecl). RESULTS AND DISCUSSION: The frequency of PE
Ecl is 5.33%. Praeeclampsia and Eclampsia were found (monitored) during two
consecutive pregnancies in one of the PWWE. Six patients were with severe
Praeeclampsia and one of them was with data of HELLP syndrome. There were three
cases with Eclampsia. Delivery by surgery was made in 8 cases, (7 patients, but
for one of them twice). The other 4 pregnant women with moderate Praeeclampsia
got delivery per vias naturales. Epileptic seizures during pregnancy were
recorded for 5 of PWWE. One patient was with generalized clonic-tonic seizures
and 4 other were with partial seizures. During the period 24 hours after delivery
seizures were noted for 4 patients. Six PWWE were without therapy with
antiepileptic drugs (AED). Three of them started monotherapy with AED during
pregnancy. One other patient with pharmacoresistant symptomatic epilepsy
(meningiomas of the brain with two neurosurgical operations) was on polytherapy
with 3 AED during the whole pregnancy. The EEG study showed focal activity
predominantly occipital, occipito-temporal and parieto-occpital. CONCLUSIONS: The
detection of arterial hypertension and proteinuria in PWWE should focus attention
on PE-Ecl. The united active clinical monitoring and treatment by a neurologist
epileptologist and obstetrician is the most accurate clinical behavior.
PMID- 27509653
TI - [HEAD INJURY DURING PREGNANCY].
AB - No matter how severe is head injury during pregnancy, it can threaten both- the
maternal and (or) the fetal life. The risk derives from systemic and cerebral
consequences of high intracranial pressure, hypotension, anemia or expanding mass
lessions in the cranial cavity. The specific hormonal background of the mother
may contribute the better outcome after traumatic brain injury (TBI). Pregnancy
and trauma push the doctors to create different and specific management than the
usual case. Investigating literature data we figure out the initial assessment,
management priorities for resuscitation of the head injured pregnant patient,
concidering the specific anatomic and physiologic changes during pregnancy. We
accept the principal: first save the mother, then the child, if possible,
proposing algorithm for severe head injured pregnant patient management.
PMID- 27509654
TI - [FREQUENCY AND MEDICAL SOCIAL ASPECTS PREMATURE BIRTH].
AB - Premature birth (PB) remains an unresolved problem, despite progress in prenatal
medicine and the introduction of new methods and techniques of prolonged
respiratory resuscitation in recent decades. Premature birth is the cause of 70%
of neonatal mortality and 50% of long-term neurological complications in
newborns, many of whom debilitating. Notwithstanding the significant progress
prenatal care in the last twenty years in developed countries is a trend towards
a gradual and continuous increase in premature births. PB is not only medical but
also social problem. Despite the efforts of the scientific and practical
obstetrics and modern tocolytic therapy, the rate of premature births in the last
decade reduced. The causes of preterm birth are multifactorial and vary depending
on gestational age, genetic factors and environmental factors. The long-term
consequences of premature birth bear behind not only economic but also social
problems. In many developing countries, premature birth is a major cause of
disability. Clinical studies in recent years have been aimed at creating a
comprehensive therapeutic algorithm behavior in premature births in order to
reduce their frequency, especially for those born weighing less than 1000g.
PMID- 27509655
TI - [ZIKA--VIRUS INFECTION].
AB - This review summarizes the knowledge of the scientific community for Zika-virus
infection. It became popular because of severe congenital damage causes of CNS in
newborns whose mothers are infected during pregnancy, as well as the risk of
pandemic distribution. Discusses the peculiarities of the biology and ecology of
vectors--blood-sucking mosquitoes Aedes; stages in the spread of infection and
practical problems which caused during pregnancy. Attention is paid to the
recommendations that allow leading national and international medical
organizations to deal with the threat Zika-virus infection.
PMID- 27509656
TI - [THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].
AB - Morbidity and mortality from lung cancer has dramatically increased in women as
compared to men over the past few years. Historically, smoking has been
considered the major risk factor for lung cancer regardless of gender. Several
recent lines of evidence implicate gender differences in the observed differences
in prevalence and histologic type which cannot be explained based on the
carcinogenic action of nicotine. Several recent studies underscore the importance
of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung
cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000
women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is
extremely sensitive to estrogens. The latter act directly or as effect modifiers
for the relationship between smoking and lung cancer. Further research examining
the relationship between serum estrogen levels and the estrogen receptor
expression in normal and tumor lung tissue samples can help elucidate the
importance of reproductive and hormonal (exogenous and endogenous) factors in the
carcinogenesis of lung cancer.
PMID- 27509657
TI - [ASSISTED REPRODUCTIVE TECHNOLOGIES AND OVARIAN CANCEROGENESIS].
AB - Development of assisted reproductive technologies (ART) for treatment of
infertility poses many questions about potential involvement of the drugs used in
ART in the process of ovarian carcinogenesis. The presence of other etiological
factors makes the assessment of risks implied by administering these drugs rather
difficult. The results obtained in the study are controversial and inconclusive,
yet theoretical and epidemiological data suggest that caution is needed in IVF
patients, receiving such drug therapy.
PMID- 27509658
TI - [DISSEMINATED PERITONEAL LEYOMYOMATOSIS--PRACTICAL APPROACH TO DIAGNOSIS].
AB - Disseminated peritoneal leiomyomatosis (DPL) is a rare condition characterized by
the presence of multiple histologically benign smooth muscle nodules on the
surface subperitoneal tissue simulating macroscopic peritoneal carcinomatosis.
This disease is rare, but in recent years, in connection with the widespread
introduction of laparoscopic surgery, the reports of disseminated peritoneal
leiomyomatosis occurring after laparoscopic morcellation, were frequent. The
knowledge of DPL is necessary to develop methods of prevention, and
individualized treatment depending on the pathogenesis and clinical
manifestations in each patient.
PMID- 27509659
TI - [TORSION OF FALLOPIAN TUBE LEIOMYOMA TREATED BY LAPAROSCOPY].
AB - Leiomyomas of the Fallopian tubes are rare and their correct diagnosis is
extremely difficult. Usually they are incidental findings seen at autopsy or
unrelated surgical procedures: A 34-year-old woman presented with lower abdominal
pain. Transvaginal ultrasound revealed a solid 7 cm extrauterine mass. Both
ovaries are normal. Our preoperative diagnosis was torsion of the fallopian tube
due intratubal leiomyoma. Laparoscopic surgery was performed and the leiomyoma
was found to have originated from the isthmus of the right Fallopian tube.
Laparoscopic myomectomy was performed with preservation of the ramus tubarius
dextra. The histological examination concluded to a leiomyoma with ischemic
changes. We report a case of torsion of a tubal leiomyoma, which was successfully
managed laparoscopically.
PMID- 27509660
TI - [POLYGYNAX IN THE TREATMENT OF VAGINAL INFECTIONS IN PREGNANT AND NON-PREGNANT
WOMEN--CLINICAL EXPERIENCE].
AB - Vaginal infections /VI/ represent some of the most common diseases by infection
of FGS. The aim of this study is to analyze clinical and bacteriological efficacy
of Polygynax in the treatment of vaginal infections and to take into account the
correlation between the results of microbiological controls and reduction of
clinical symptoms. The study included 100 patients, including 50 pregnant and non
pregnant 50 for a period of 3 months. All of them was diagnosed with vaginitis
clinical examination, taken material from vagina for microbiological testing. The
studied women was conducted targeted therapy Polygynax 12 capsules, in the form
of vaginal capsules for 12 days, after which the sample control microbiology.
Behind the subjective complaints of the patient and to reduce them as a result of
treatment. The effective implementation of Polygynax 12 capsules is equally good
as in non-pregnant and pregnant women. In a summary of the survey data to make
relevant analyzes and conclusions from the results.
PMID- 27509661
TI - [ENDOMETRIOSIS FERTILITY INDEX].
AB - In women suffering from endometriosis and infertility, the decision as to when
and how to perform surgical excision and/or fertility treatment is mainly based
on clinical guidelines and expert opinions. However, so far data from randomized
controlled trials or meta-analyses to answer the question whether surgical
treatment of moderate to severe endometriosis can indeed enhance pregnancy rates
compared with expectant management are lacking, as not all studies report
fertility outcome or supply sufficiently detailed information. The most
frequently used staging system for endometriosis is the revised American
Fertility Society (rAFS) score (ASRM, 1997). Unfortunately, this classification
system has some serious limitations, including not effectively predicting
clinical outcomes of treatment, especially pregnancy rates in infertile patients.
For this reason, Adamson and Pasta (2010) developed the endometriosis fertility
index (EFI). EFI is a scoring system which includes assessment of historical
factors at the time of surgery (age, duration of infertility and pregnancy
history), of adnexal function at conclusion of surgery (functional score of
Fallopian tubes, fimbriae and ovaries bilaterally), and of the extensiveness of
endometriosis (rAFS endometriosis lesion score and total rAFS score). The EFI is
intended as a clinical tool to counsel patients on the approach towards fertility
after surgery.
PMID- 27509662
TI - [POLYHEXAMETHYLENE BIGUANID HYDROCHLORIDE (BIGUANELLE) THERAPY OF BACTERIAL
VAGINOSIS].
AB - The aim of our study was to determine the efficacy and tolerability of local
therapy with polyhexamethylene biguanid hydrochloride (BIGUANELLE) in women with
anaerobic vaginal infection. MATERIAL AND METHODS: We include in our study 23
women (18-50) with established by AMSEL criteria bacterial vaginosis. In all of
the women at the beginning and at the end of the survey was performed
gynecological examination and microbiological research (AMSEL). The therapeutic
scheme at all women is with a single vaginal application of gynecological
solution BIGUANELLE. Effectiveness of the treatment was evaluated according to
clinical complaints and microbiological research (Amsel criteria: Ph 4.5 >; KOH
(+); "clue cells"; specific vaginal fluorine). Tolerability of patients to
treatment was assessed by questionnaire. RESULTS: Clinical complaints of patients
after the therapy decreased as follows: vaginal fluorine with 73.9%; odor--75%;
pruritus--50%; discomfort--90%. Microbiological research and their evaluation by
AMSEL, showed the therapeutic efficacy of the therapy in 16 (69.6%) of all (n-23)
patients. At 7 (30.4%) women, the treatment remained without effect. At
questionnaire answers, 73.9% patients were satisfied with the application of
BIGUANELLE, 95.6% of them have implemented it easily, 95.6% of women believe that
BIGUANELLE is more convenient to use in comparison with similar products which
have a daily application, and none of the patients (100%) have any complaints in
applying this gynecological solution. CONCLUSIONS: BIGUANELLE showed good
clinical efficacy in the treatment of bacterial vaginosis. It is easily applied
and well tolerated by the patients.
PMID- 27509663
TI - [FETAL THERAPY: INTRAUTERINE THORACO-AMNIOTIC SHUNTING IN MACROCYSTIC TYPE CYSTIC
ADENOMATOID MALFORMATION OF THE LUNG: REVIEW OF THE LITERATURE AND CASE REPORT].
AB - ABSTRACT OBJECTIVE: To present a case of macrocystic type cystic adenomatoid
malformation of the lung (CCAM) treated with thoraco-amniotic shunt and to review
the published data to evaluate the efficiency of thoraco-amniotic shunts for
drainage of (CCAM). MATERIALS AND METHODS: This wass case reported of a fetus
with a large thoracic cyst, major mediastinal shift and polyhidramnion treated
with thoraco-amniotic shunting. We identified 8 cases diagnosed with CCAM and
only one case met the criteria for fetal surgery. Thoracoamniotic shunting was
successfully performed under local anesthesia and ultrasound control with
operating time of 35 minutes. Medline was searched to identify cases of CCAM
treated by thoraco-amniotic shunting. RESULTS: Fetal therapy forlung lesion was
successfully performed at 30 weeks of gestation with CCAM volume ratio > 1.6
January, 2015 and amniodrenage after the procedure was carried out. The pregnancy
has progressed uneventfully and planned Cesarean section was performed at 38
weeks of gestation. The optimal management of such case was performed for the
first time in Bulgaria, which required an experienced interdisciplinary team. The
newborn underwent resection of the lesion with no growth or neurodevelopment
delay. The literature search identified cases with CCAM treated with thoraco
amniotic shunting between 1987 and 2016 and the the survival rate of non-hydropic
fetuses that underwent treatment was 88%. CONCLUSIONS: Thoraco-amniotic shunting
for macrocystic type CCAM is associated reduced risk of fetal intrauterine death
and is also likely to be beneficial for the following major postnatal surgery
PMID- 27509664
TI - [COMPLICATION AFTER UNRECOGNIZED ECTOPIC PREGNANCY--A CASE REPORT].
AB - The authors present a clinical case of performing an abortion at patient with
unrecognized ectopic pregnancy and subsequent complication- perforation of the
uterus and the colon and life-threatening haemoperitoneum.
PMID- 27509665
TI - [UTIPRO PLUS CAPSULE, A NEW INNOVATIVE APPROACH FOR THE TREATMENT OF CYSTITIS AND
OTHER BACTERIAL URINARY TRACT INFECTIONS].
PMID- 27509666
TI - [FEMINORM OSTEO - A MENOPAUSE AND HEALTHY BONES APPROACH].
PMID- 27509667
TI - [IS THERE A PLACE FOR VIA AND VILI IN OUR PRACTICE].
AB - The aim of this review is to discuss the possibilities and disadvantages of the
techniques for visual inspection of the uterine cervix with acetic acid (VIA) and
with Lugol's iodine (VILI) for early detection of cervical neoplasia. Efficient
cervical screening method, approved in practice, is cytology--PAP smear. The lack
of organized screening program in Bulgaria is the reason why a lot of cases of
cervical cancer are missed or diagnosed late. This raises the question for
searching alternative tests to assess the uterine cervix that do not use special
techniques and have a reasonable cost. Published results show that VIA and VILI
represent an appropriate alternative for cervical screening. The results of VIA
and VILI are immediately available and do not require any laboratory processing.
CONCLUSION: Both types of visual inspection of the uterine cervix are easy to
accomplish, fast--the result is available at the moment of inspection, they do
not require special equipment, the correlation between sensitivity and
specificity is good and last but not least--they have low price. VIA and VILI
have certain position in our practice.
PMID- 27509668
TI - [Paracrine properties of Mesenchymal Stromal Cells].
AB - Mesenchymal stromal cells are multipotent cells found in a large number of adult
tissues. Their ability to participate in the repair of these damaged tissues is
the origin of the enthusiasm that they elicit in the field of cell therapy. It
gradually became apparent that their ability to change a pathological environment
is more related to their ability to modulate the behavior of other cell types
than their capacity of diferentiation. Recent years have expanded the scope of
our knowledge about their way of communication with their environment but also
the amount of information that they receive from this environment. In this brief
review, we will present some of the mechanisms by which MSCs can communicate
remotely with other cell types and how it currently appears possible to direct
the secretion pattern of these cells.
PMID- 27509669
TI - [Not Available].
AB - In solid organ transplant, immunosuppressive therapy helped to increase graft and
patient survival. However, these treatments are associated with toxic risks and
infectious or tumor complications. The identification of immunoregulatory
properties of regulatory cells and in particular Mesenchymal Stem Cells opens new
therapeutic perspectives in the prevention of acute rejection and for the
treatment of chronic rejection. In this review we will describe immunoregulatory
properties of these cells and their potential use in solid organ transplantation.
PMID- 27509670
TI - [Not Available].
PMID- 27509671
TI - [Not Available].
PMID- 27509672
TI - [On the borders of the neurology and the rheumatology].
AB - The links between the rheumatology and the neurology, are ancient and established
of one intricacy of pathologies and symptoms. It is not a question here of
approaching the inflammatory myositis nor the neurological, essentially central
signs, during the inflammatory diseases still called systematic as the lupus or
the syndrome of Gougerot-Sjogren, neither compression occurring during rheumatoid
arthritis and ankylosing spondylarthritis. It is not either a question of
reviewing the compression of osseous origin, as for example the narrow cervical
spine, the narrow lumbar spine or the basilaire impression during the bony
disease of Paget. Some neurological pathologies can put off the track or mislead
the clinician towards symptoms which could impose it for radiculopathy origin
occurring in rheumatic conditions In the second place, there are untidy or
underestimated neuropathies which deserve a particular attention.
PMID- 27509673
TI - [Chronic pain: emotional and cognitive consequences].
AB - Chronic pain which had become a major public health problem, is always
accompanied with emotional and cognitive disorders. These comorbidities are
circular and auto generated as in low back pain or in somatoform pain as
fibromyalgia. Cerebral imagery of pain show the superposition of emotional and
cognitive circuits especially in frontal regions from where come the descending
control of pain. Therefore common areas regulate the three functions.
Consequences on semiology and treatment of chronic pain are discussed.
PMID- 27509674
TI - [Chronic pain management: societal impact].
AB - Pain is a real issue of public health, quality and evolution of a system of
health test: this is a major social problem. Pain management meets a humanistic,
ethical purpose and dignity of man because of the physical and psychological
implications. It induces a disability which excludes the patient of society
gradually or suddenly. The physical pain and mental suffering to all ages of life
make more vulnerable people weakened by disease. Rebel chronic pain are sources
of disability, disabilities, disability and major alterations in the quality of
life. All of these data shows the impact of pain and its intensity on the
professional conditions, on professional activity and productivity, on the use of
care systems (very significant increase in medical consultations,
hospitalizations), as well as on the mental and physical health. These results
confirmed analyses which consider that the unrelieved pain has a major economic
impact on care systems and constitutes a public health problem with around two
thirds of persons professionally impacted by pain. The progress of medicine has
helped the healing of certain serious diseases, but also favoured acute diseases
to turn to chronic diseases. The result is an increase in of lifetime sometimes
without disease, but this survival may be also accompanied by disease or
disability. Progress, pain and suffering, the end of life, ethics will be the
core of the basic thoughts of tomorrow.
PMID- 27509675
TI - [CONCLUSION].
PMID- 27509676
TI - [Not Available].
PMID- 27509677
TI - [Not Available].
AB - After the second World War, during which medicine was manipulated to serve an
ideology, a deep movement arised to protect human beings. In 1964, Helsinki
declaration was adapted to protect persons involved in medical research. In 1988,
the Seruscalt-Huriet law introduced the obligation of informed consent. In 1994
the bioethics law introduced the notion of care consent. The March 2002 law
created the notion of health care system "user". The general philosophy of the
law was to give a larger autonomy to the patient. The various heath crises,
contaminated blood crisis, mad cow disease, human growth hormone, hospital borne
infections, were triggers for the development of patients' associations. The
health system appeared fallible. Compagnon report aim is to increase the role of
patients' associations in the health system at every level. The "health
democracy" term has been coined to place the "political democracy" and "social
democracy" concepts face to face. Internet information has transformed the
patient into a knowledgeable person. Has it made him an expert? The
doctor/patient duality is by essence asymmetric. Public health decisions are
constrained by the economical context. The democracy paradox lies in the
impossibility to be at the same time a representative anda decision maker.
Personal interest collides with common interest. An alliance between
representatives of patient's, heath system actors, politics and financers should
be knotted to build up a new heath care system.
PMID- 27509678
TI - [Not Available].
AB - To date, work on health democracy has never dealt with relationships between
patient associations and the pharmaceutical industry. The emergence of a genuine
health citizenship depends, however, to a great extent on the quality of such a
relationship. This communication, which is based on a survey of 1742 patient
associations and 270 French-pharmaceutical companies, conducted by BVA upon
request of the Ethics Commitee of the French association of pharmaceutical
companies (CODEEM) highlights the significance of the ethical issues. Beyond the
financial issue, the relationship between patient associations and pharmaceutical
companies raises the issue of associations governance, and reveals the limits of
"association expertise" but also a high expectations for effective partnerships.
PMID- 27509679
TI - [Patients' associations and clinical research--academic and industrial].
AB - The notion of "health democracy" was introduced as a core principle into the
French health law in 2002. Accordingly, stronger individual rights were
recognized to patients and, at the same time, patients' representatives have
progressively served at all levels of the governance of health system. In
clinical research, it is mandatory since 2004 that institutional review board
include patient representatives (I). Patient associationsplay a role in clinical
research in financing and/or helping to organize clinical trials. In addition,
associations play a role in protecting patients from abusive research--as well as
from being possibly not solicited as a subject in trials that could open access
to medical innovation. There is no question that, with the support of
associations, a patient with HIV or myopathy--eligible but who was not solicited-
will obtain to participate in a trial of his or her choice (II). If the role of
patients' association in health democracy has become both unquestionable and
important, it is nevertheless limited. Patients may be disadvantaged if no
combative association is committed on their disease. Patients' associations' role
is no substitute to that of the State and the law-only able to devote equitable
rights to individuals (III).
PMID- 27509680
TI - [Not Available].
PMID- 27509681
TI - [Pendred syndrome and nonsyndromic related deafness: a same entity?].
AB - Pendred syndrome is an autosomal recessive familial disorder, defined as a
sensorineural deafness coinciding with a goiter related to an iodine
organification defect. It constitutes 4 to 10 % of all causes of familial
congenital hearing loss. It is now well established that this condition was
caused by mutations in the SLC26A4 gene which codes for pendrin, a protein
involved in the transport of anions (I-, Cl, HCO3-), particularly in apical
iodine efflux in thyroid cells and chloride (Cl-|HCO3-) at the cochlear level. A
current issue is to determine factors that distinguish Pendred syndrome from
other varieties of isolated deafness also including enlargement of the vestibular
aqueduct, but without evidence of thyroid expression. A prospective investigation
of these 2 situations, conducted in Lille, leads us to redefine diagnostic
criteria and assessment methods, and to discuss genetic or environmental factors
contributing to the phenotypes.
PMID- 27509682
TI - [Lyme borreliosis and co-infections. Place of Anaplasma phagocytophilum and
Bartonella henselae].
AB - Lyme borreliosis (LB) is certainly the most common infection transmitted through
the bite of Ixodes in Northern Hemisphere. These ticks are also able to transmit
other microorganisms such as the bacteria Anaplasma phagocytophilum (Ap) and
Bartonella henselae (Bh), with the latter discovered fairly recently, leading to
diferent clinical presentations often close to those of LB. The aim of this study
was to evaluate the frequency of co-infection by either of these bacteria in
patients with LB, particularly when a treatment with beta-lactam antibiotic was
only partially effective. Of these patients, on the basis of serological data,
8.07% were simultaneously contaminated by Bh, 6.83% by Ap and 4.96% were co
infected by Bh and Ap. Since the choice of an antibiotic should take into account
the specificities of these germs and especially their intracellular
proliferation, these results should be considered in selecting treatment.
PMID- 27509683
TI - [Not Available].
AB - Evaluation and research of quality factors in surgery necessitates the
consideration of 3 types of indicators: indicators of structures, indicators of
processes and indicators of outcomes. We used these 3 types of indicators to
assess the quality of thyroid surgery and to evaluate quality indicators. These
studies allowed us to demonstrate the importance of a permanent monitoring of the
outcomes of the thyroid surgery and the presence of human and organizational
factors in the mechanisms of the surgical complications. This type of evaluation
and research in quality of health care should be extended to all the surgical
subspecialties.
PMID- 27509684
TI - [New approach for managing microbial risks in food].
AB - The aim of the food legislation is to ensure the protection of human health.
Traditionally, the food legislation requires food business operators to apply
good hygiene practices and specific procedures to control foodborne pathogens.
These regulations allowed reaching a high level of health protection. The
improvement of the system will require risk-based approaches. Firstly, risk
assessment should allow the identification of high-risk situations where
resources should be allocated for a better targeting of risk management. Then,
management measures should be adapted to the health objective. In this approach,
the appropriate level of protection is converted intofood safety and performance
objectives on the food chain, i.e., maximum microbial contamination to fulfil the
acceptable risk level. When objectives are defined, the food business operators
and competent authorities can identify control options to comply with the
objectives and establish microbiological criteria to verify compliance with these
objectives. This approach, described for approximately 10 years, operative thanks
to the development of quantitative risk assessment techniques, is still difficult
to use in practical terms since it requires a commitment of competent authorities
to define the acceptable risk and needs also the implementation of sometimes
complex risk models.
PMID- 27509685
TI - [The Emergence of Ebola virus in humans: a long process not yet fully
understood].
AB - Since 1976 Ebola virus regularly has caused small deadly outbreaks in Central
Africa, usually controlled in a few months. For the first time, an Ebola epidemic
of exceptional magnitude dramatically engulfed several countries in West Africa
since December 2013. Major failures of implementing measures to prevent human-to
human transmissions are the main cause of this large-scale Ebola outbreak. After
about one-week incubation period, the Ebola virus disease is characterized by a
sudden onset of high fever leading to multiple hemorrhages and to widespread
organ failure. Several bat species constitute the main reservoirs of Ebola
viruses. Human contamination would occur either directly from bats, widely
consumed by the local populations, or through animal species susceptible to Ebola
infection, such as chimpanzees and gorillas. Alongside this "natural cycle", an
"epidemic cycle" involving domestic animals living in villages such as dogs or
pigs, is seriously suggested. Thus, according to the diversity of concerned
animals and their clinical infectionform, modalities of human contamination can
be multiple and are still largely unknown. In this context, all efforts that
could be made to unravel the mystery of the Ebola virus emergence in humans and
clarify modalities of the virus transmission, would allow for predicting or for
anticipating the future occurrence of epidemics. This review aims to provide an
exhaustive inventory of the Ebola ecology to highlight events governing the virus
transmission to humans that still remain unsolved.
PMID- 27509686
TI - [NADPH oxidase Nox4, a putative therapeutic target in osteoarthritis].
AB - The NADPH oxidases, Nox, are transmembrane hemoproteins, whose exclusive function
is to reduce molecular oxygen to produce superoxide anion O2 degrees - and
consequently highly reactive oxidant and toxic oxygen species, ROS. Among the 7
NADPH oxidases expressed in humans, Nox4 is the sole Nox isoform present in human
primary chondrocytes. Nox4 was suggested as one of the main actors involved in
cartilage degradation in osteoarthritis. The stimulation of chondrocytes, the
only cell present in cartilage, by IL-1beta results in the activation of Nox4.
This leads to an increase of ROS production which in turn could regulate
signaling pathways sensitive to oxidative stress such as gene-encoding matrix
metalloproteases MMP1, MMP13 and Adamalysin ADAMTS4. A deep understanding of Nox4
structure/function and mechanisms of regulation could lead both to the
identification of new therapeutic targets and to the development of innovative
strategies for appropriate osteoarthritis treatment.
PMID- 27509687
TI - [Bela Bartok's disease: a hidden leukemia, a defeated leukemia].
AB - The hematological disorder Bela Bartok suffered during his exile in the United
States and that led to his death has long remained mysterious, as well as the
lung disease that accompanied it. The present historical evocation offers us the
opportunity to explain the remarkable biological and therapeutic advances
obtained in the field of chronic myelocytic leukemia during the last decades.
PMID- 27509688
TI - [Not Available].
PMID- 27509689
TI - New assessment tool ready to help prevent pressure ulcers.
PMID- 27509690
TI - Same-day discharge attracts droves of total joint patients.
PMID- 27509691
TI - Beyond sponges: Safe practices for avoiding all RSIs.
PMID- 27509692
TI - Top 10 Patient Safety Concerns for 2016.
PMID- 27509693
TI - Protocols control glycemic levels in diabetic surgical patients.
PMID- 27509694
TI - Experts can help ASC leaders solidify building safety.
PMID- 27509695
TI - Communications.
PMID- 27509696
TI - An Evidence Update from Peer Assistance Program in Nursing (PAPIN).
PMID- 27509697
TI - The Imperative: Integrating Evidence-Based Practice into the Clinical Nurse
Leader (CNL) Role.
PMID- 27509698
TI - Anorectal manometry in dyssynergic defecation: Are we there yet?
PMID- 27509699
TI - Renal disease in patients infected with hepatitis B virus.
AB - Infection with hepatitis B virus (HBV) can result in hepatic diseases which may
include an asymptomatic non-replicative carrier state, immunotolerant phase
characterized by high DNA levels without significant hepatic injury, immune
reactive phase characterized by occurrence of chronic hepatitis and fibrosis in
the liver, or complications like cirrhosis or hepatocellular carcinoma.
Extrahepatic manifestations may also accompany HBV infection. These may include
serum sickness syndrome, polyarthralgia, polyarthritis, dermatologic
manifestations like pitted keratolysis, urticaria, purpura, oral lichen planus or
Gianotti-Crosti syndrome-a childhood papular eruption. Renal involvement may
occur with HBV infection and usually involves glomerular or vascular injury.
Various morphologic forms of renal injury have been reported with HBV infection,
the commonest being membranous glomerulonephritis. The manifestations may include
swelling over face and body, pedal edema, and urinary abnormalities. Evaluation
may detect proteinuria, hematuria and reduction in estimated glomerular
filtration rate (GFR). The management options include use of antiviral drugs
targeting HBV infection with or without concomitant immunosuppressive medication.
With availability of newer drugs like entecavir and tenofovir, these have become
the first line agents as they have a high barrier to resistance. Sole use of
immunosuppression is not recommended for lack of clear benefit and the possible
risk of HBV reactivation or flare.
PMID- 27509700
TI - Predictors of outcome after reconstructive hepatico-jejunostomy for post
cholecystectomy bile duct injuries.
AB - INTRODUCTION: Reconstructive hepatico-jejunostomy is recommended for major bile
duct injuries (BDIs) during cholecystectomy. Complications of biliary leak,
cholangitis, bleeding, anastomotic strictures and biliary cirrhosis remain a
major concern affecting a patient's outcome after surgery. The aim of this study
was to analyse the results of surgical repair of major BDIs at our institution
and identify predictors for the development of major complications. METHODS: A
retrospective study of 57 patients with major BDI after cholecystectomy referred
to a tertiary hepato-biliary centre from July 1999 to July 2011 and subsequently
managed with reconstructive bilio-enteric anastomosis was performed. RESULTS: Of
57 patents 35 (61.4%) were primary referred. 22 (38.6 %) were secondary referred,
of which 17 were for correct reconstructive surgery performed elsewhere and 5
were following attempted endoscopic management. 17 (29.8%) had local and systemic
perioperative complications. 13 (22.8%) had major complications (bile leak,
bleed, stricture and/or biliary cirrhosis). No association was found between age,
type of cholecystectomy, type of injury, vascular injury and occurrence of major
complications. Secondarily referred patients after therapeutic interventions (p =
0.010) and reconstructive surgery after repair performed by non-specialists
suffered an increased incidence of major complications (p = 0.032). Secondary
referral was also an independent predictor of major complications (p = 0.024).
CONCLUSION: Early referral of patients with no previous intervention to a
tertiary hepato-biliary center and specialist surgical repair is recommended for
improved outcome after reconstructive hepatico-jejunostomy for major BDIs during
cholecystectomy.
PMID- 27509701
TI - Multidetector computed tomography evaluation of post cholecystectomy
complications: A tertiary care center experience.
AB - OBJECTIVE: To evaluate the role of multidetector computed tomography (CT) and CT
angiography (CTA) in post cholecystectomy complications. METHODS: A retrospective
analysis of data from December 2012 to August 2014 was performed. Eight hundred
sixty consecutive patients with history of cholecystectomy (laparoscopic or open)
were evaluated. After exclusion of 645 patients with normal imaging, analysis for
post cholecystectomy complications was performed in 215 patients. A contrast
enhanced CT/CTA was performed. Mean interval to imaging was 10 months (range 3
days to 15 months). RESULTS: A complication rate of 25% was noted in patients
undergoing imaging following cholecystectomy. Gallbladder bed or perihepatic
collections were seen in 11.9% cases (n = 103). Intrahepatic biliary radicle
dilatation (IHBRD) was seen in 7% patients (n = 60). Isolated right or left
ductal dilatation was seen in 9 patients; rest of the patients had bilateral
IHBRD. Cholangitic abscesses and mild acute pancreatitis were seen in 11 (1.2%)
and 12 (1.3%) patients respectively. These comprised biliary complications.
Venous thrombosis involving the portal vein was the most frequently encountered
vascular complication (n = 12). Right hepatic artery pseudoaneurysm was seen in
two patients. Less common complications were abdominal wall hematoma (n = 2),
incisional hernia (n = 6), port site hernia (n = 2), large bowel injury (n = 1),
biliocutaneous fistula (n = 1) and enterocutaneous fistula (n = 1). CONCLUSION:
CT allows classification of post cholecystectomy complications and guides further
management. CTA provides an efficient road map for management of vascular
complications.
PMID- 27509702
TI - Solitary rectal ulcer syndrome: clinical, endoscopic, histological and anorectal
manometry findings in north Indian patients.
AB - BACKGROUND: Solitary rectal ulcer syndrome (SRUS) is a chronic, benign defecation
disorder often related to excessive straining. SRUS is diagnosed on the basis of
clinical symptoms, endoscopic and histological findings. METHODS: All patients
diagnosed with SRUS by colonoscopy and confirmed by histopathology from October
2012 to August 2014 in the Department of Gastroenterology, Institute of Medical
Sciences, Banaras Hindu University, India, were included in the study. Out of 92
patients, thirty-four patients underwent anorectal manometry. Twenty age-matched
healthy volunteers were also studied with anorectal manometry to serve as
controls. RESULTS: Mean age of the group was 41 +/- 19 years with age range of 10
82 years; males were 58 (63%) with male to female ratio of 1.7:1. Bleeding per
rectum was present in 83%, constipation in 46.7%, abdominal pain in 27.2%, and
diarrhea in 25% of the patients. On endoscopy, ulcerative lesions were seen in
83% patients of whom solitary and multiple lesions were present in 44% and 39%,
respectively. Polypoidal lesions were reported in 17.4% whilst rectal polyps and
erythematous mucosa were found in 5.4% and 2.2%, respectively. Histological
examination revealed fibromuscular obliteration in 100% of patients, surface
ulceration in 70.6% and crypt distortion in 20.65% of patients. Anal relaxation
and balloon expulsion test was significantly abnormal in SRUS patients compared
to healthy controls (53% vs. 20%, p < 0.01). CONCLUSION: Rectal bleeding was the
most common symptom and ulcerative lesions the most common endoscopic finding.
Fecal evaluation disorder was more prevalent inpatients with SRUS.
PMID- 27509703
TI - Efficacy of aspiration in amebic liver abscess.
AB - BACKGROUND: Amebic liver abscess (ALA) is a common and serious problem in our
country. There are only a few controlled trials on the efficacy and advantages of
combination therapy with percutaneous needle aspiration and pharmacotherapy, over
pharmacotherapy alone for amebic liver abscess. MATERIAL AND METHODS: This study
was conducted to compare the efficacy of two different treatment modalities i.e.
drug treatment alone vs. drug treatment and aspiration of abscess cavity in
patients with small (up to 5 cm) and large (5 cm to 10 cm) size ALA. This is one
of the largest single center, prospective, randomized studies comparing the
efficacy of aspiration in ALA. RESULTS: (i) Mean body temperature, liver
tenderness, total leukocyte count (TLC), serum alanine aminotransferase (ALT) and
liver span were significantly decreased in the aspiration group on days 8 and 15
as compared to non-aspiration group especially in large abscess (5 cm to 10 cm).
(ii) Abscess cavity maximum diameter decreased significantly in aspiration group
on days 8 and 15, and 1 month & 3 months in large abscess (5cm to 10 cm).
CONCLUSIONS: (i) Needle aspiration along with metronidazole hastens clinical
improvement especially in large (5 cm up to 10 cm) cavities in patients with ALA.
(ii) Aspiration is safe and no major complications occurred. (iii) Hence,
combination therapy should be the first choice especially in large ALA (5 cm to
10 cm).
PMID- 27509704
TI - Validation of Boey's score in predicting morbidity and mortality in peptic
perforation peritonitis in Northwestern India.
AB - BACKGROUND: The major complications of peptic ulcer are hemorrhage, perforation
and gastric outlet obstruction with perforation occurring in about 2-10% of
patients. Patients with perforated peptic ulcer still have a high rate of
morbidity and mortality and to improve the outcomes it is important to stratify
the patients into different categories. AIMS: To evaluate the accuracy of Boey
scoring system in predicting postoperative morbidity and mortality in patients
operated for peptic perforation. METHODS: It was a prospective observational
single centre study conducted at SMS Medical College and Hospital, Jaipur, from
October 2011 to October 2012 on 180 patients undergoing open surgery for peptic
ulcer perforation. Postoperative outcomes in terms of recovery and complications
were studied. For prediction of morbidity and mortality by Boey risk
stratification, the odds ratio (OR) and 95% confidence interval (95% CI) of each
risk score were compared with the outcomes of "0" risk score. RESULTS: The
mortality rate increased progressively with increasing numbers of the Boey score:
1.9%, 7.1%, 31.7% and 40% for 0, 1, 2, and 3 scores, respectively (p < 0.001).
The morbidity rates for 0, 1, 2, and 3 Boey scores were 13%, 45.7%, 70.7% and
73.3% respectively (p < 0.001). CONCLUSIONS: Boey score is a useful tool for
assessing the prognosis of operated cases of peptic perforation and helps in the
assessment of mortality and morbidity of these patients.
PMID- 27509705
TI - An unusual case of histiocytic sarcoma.
PMID- 27509706
TI - Acute intermittent porphyria: a missed diagnosis in pre-pubertal children with
recurrent abdominal pain.
PMID- 27509707
TI - Altered sensorium in a chronic alcoholic: pancreatic encephalopathy, Wernicke's
encephalopathy or Marchiafava Biganami disease?
PMID- 27509708
TI - Chylous ascitis post primary living donor liver transplantation managed by
dietary modification.
PMID- 27509709
TI - Endoscopic biopsy: a simple guide for beginners.
PMID- 27509710
TI - Successful living donor liver transplantation with partial nephrectomy for co
existing renal cell carcinoma and cirrhosis.
PMID- 27509711
TI - Pancreatic endotherapy in management of pancreatopericardial fistula.
PMID- 27509712
TI - Periampullary gastrointestinal stromal tumor presenting with obstructive
jaundice.
PMID- 27509713
TI - Primary extraskeletal osteosarcoma of gall bladder.
PMID- 27509714
TI - Endotipsitis caused by extremely drug-resistant Klebsiella pneumoniae.
PMID- 27509715
TI - Giant choledochal cyst in infancy--A rare entity.
PMID- 27509716
TI - Incidentally detected ectopic ampulla of vater in the antrum in a patient of
colonic tuberculosis.
PMID- 27509717
TI - [Histopathological Study of the Relationship between Lymphoid Follicles and
Different Endoscopic Types of Nodular Gastritis].
AB - Nodular gastritis is characterized histologically by hyperplasia and enlargement
of lymphoid follicles in the lamina propria. With the objective of elucidating
the relationship between different endoscopic types of nodular gastritis and
lymphoid follicles, distributions of lymphoid follicles in the lamina propria
were investigated in young gastric cancer patients with nodular gastritis. For
the study, whole-mucosal step sectioning of each resected stomach was performed,
the densities of lymphoid follicles of all specimens were measured
microscopically, and the horizontal and depth distributions were calculated. For
assessment in the horizontal direction, density distribution diagrams of lymphoid
follicles were created. For assessment in the depth direction, the different
endoscopic types of nodular gastritis were compared in the five different
analysis sites. In the assessment of the horizontal distribution, no
characteristic distribution tendencies were observed in either the granular type
group or the scattered type group; however, it was found that areas with
relatively high densities of lymphoid follicles generally coincided with the
areas where nodular gastritis was observed endoscopically. These results
suggested that hyperplasia and aggregation of lymphoid follicles in the lamina
propria are involved at the sites where nodular gastritis is observed
endoscopically. In the assessment of the depth distribution, lymphoid follicles
tended to be more unevenly distributed in the upper lamina propria in the
granular type group than in the scattered type at the three different analysis
sites where nodular gastritis was observed endoscopically. These results
suggested the possibility of a granular type characteristic.
PMID- 27509718
TI - [Evaluation of the Creatine Kinase MB Activity Assay Kit].
AB - CK-MB activity, which is measured by the immunoinhibition method, is an important
marker for use in the diagnosis of acute coronary syndromes. In the present
study, we evaluated the basal performance of a recently improved CK-MB activity
kit, "L-system CK-MB," in which the activity of mitochondrial CK subunits is
inhibited. Within-run and between-day precision were in the range of 1.9-2.3% and
3.2-6.0%, respectively. Diluted linearity and limit of detection were determined
to be 600 U/L and 0.8 U/L, respectively. The use of L-system CK-MB allowed the
inhibition of the activity of 98.1% of sarcomeric mitochondrial CK, 97.7% of
ubiquitous mitochondrial CK, and 99.9% of CK-MM. The correlation coefficient (r)
between CK-MB activity and CK-MB protein was 0.968. However, we found 4 cases
showing CK-MB activity significantly higher than the protein concentration.
Increased CK-BB activity was detected by electrophoresis in these cases. In some
patients with malignant tumors, the presence of CK-immunoglobulin complex also
lead to elevated CK-MB concentrations. Thus, the discrepancy in the CK-MB
activity and the protein concentration may be caused by the presence of CK-BB
and/or CK-immunoglobulin complex. More attention needs to be focused on samples
with high CK-MB protein concentrations, especially when the CK-MB/CK ratio is
high.
PMID- 27509719
TI - [A Case of Heparin-Induced Thrombocytopenia with Discrepancy in the Results of
Anti-Platelet Factor 4/Heparin Antibodies between Latex-Particle-Enhanced
Immunoturbidimetric Assay and Enzyme Immunoassay].
AB - A female patient in her seventies with diabetes mellitus, hyper-lipidemia and
mitral regurgitation was admitted because of the acute heart failure. She was
treated with diuretics and vasodilators, however these were not effective.
Therefore the CHDF using heparin was required for the patients. After the
introduction of CHDF, the platelet count subsequently decreased to less than 7.0
x 10(4)/MUl. After stopping CHDF, the platelet count recovered. In the second
CHDF treatment, the platelet count decreased again. HIT was suspected because of
both the usage of heparin and five points of 4T's score in the patient. Heparin
was discontinued immediately and then her platelet count improved. The HIT
antibody by latex-particle-enhanced immunoturbidimetric assay was performed
simultaneously, however it was not detected. After re-using heparin by heparin
lock, platelet count had been decreasing. Furthermore the thrombus was observed
in the infusion tube. We considered that a clinical course did not accord with
the result of HIT antibody. We measured HIT antibody by another method, an enzyme
immunoassay (EIA), and the positive antibody was observed. We encountered a rare
case with discrepancy in the results of HIT antibody between two methods. When
HIT is suspected by the results from the clinical course and 4T's score, even
though the negative HIT antibody, heparin should be discontinued and the
different assay for HIT antibody such as an EIA in this case should be performed.
PMID- 27509720
TI - [Laboratory-Based Clinical Research I am Aiming for].
AB - We have pursued the clinical introduction of assays of lysophospholipids and
related proteins. One such example is the multi-functional lysophospholipid
mediator lysophosphatidic acid (LPA), which is produced from
lysophosphatidylcholine (LPC) through the lysophospholipase D (lysoPLD) activity
of autotaxin (ATX) in body fluids. Determination of the LPA concentration in body
fluids, especially plasma, is clinically relevant and important for diagnostic
purposes, and we have succeeded in the elucidation of disease states in which the
levels of LPA/ATX are altered; ATX is promising as a biomarker for several
diseases. The department of clinical laboratory in the hospital is a suitable
section to perform such research, for which sophisticated assays and sampling
techniques are needed.
PMID- 27509721
TI - [Emerging Technologies Support the Molecular Basis of the WHO Classification of
Hematopoietic Neoplasms].
AB - In the laboratory diagnosis of hematological neoplasms based on the WHO
classification, molecular-genetic testing is indispensable. Emerging technologies
for such testing have resulted in a shift of the assay platform from the first
generation of a single target for detection or quantitation into advanced
multiplex analysis, digital image analysis, automation of measurement, and
combination with immunophenotypic analysis. The multiplex assay has expanded its
platform application to genome-wide analysis, such as array comparative genome
hybridization, SNP array, and next-generation sequencers. These have been applied
for the diagnosis of hematopoietic neoplasms, enabling whole-genome profiling of
diseases. The application of genome-wide analysis, such as target sequencing, is
expected to be a practical tool in the laboratory diagnosis of hematopoietic
neoplasms. The clinical use of these emerging technologies would provide a
molecular basis for the WHO classification of hematological neoplasms and, thus,
promote the quality of treatment based on laboratory diagnosis.
PMID- 27509722
TI - [Clinical Laboratory Tests for Liver Diseases].
AB - A review lecture at the 60th annual meeting of the Japanese Society of Laboratory
Medicine is summarized in this paper, in which novel advancements in acute
hepatitis B, interferon therapy for hepatitis C, prediction of the liver fibrosis
stage and epidemiology, and diagnosis of hepatocellular carcinoma are presented.
Because clinical laboratory tests importantly contribute to progress in the
diagnosis and treatment of liver diseases, the lecture focused on the role of
such tests.
PMID- 27509723
TI - [Mechanism Causing Abnormal Laboratory Data--Significance of Electrophoresis and
Information Transmission--Chairmen's Introductory Remarks].
AB - Abnormal laboratory data are observed due to some kinds of modification as well
as pathological conditions of patients. Elucidation of the causal mechanism is
very important for clinical laboratories. This symposium was planned to highlight
the significance of electrophoresis. Electrophoresis is one of the most important
tools to provide clinicians with information for medical diagnosis and care.
PMID- 27509724
TI - [Electrophoretic Analysis of Abnormal Data on Serum Protein Electrophoresis].
AB - We recently demonstrated glycation of monoclonal IgA and the presence of IgA
albumin complexes, but the significance of the complexes was not clear. We
describe a non-diabetic patient with IgA type M-protein whose serum fructosamine
and glycoalbumin levels were elevated. On electrophoresis of the serum protein of
the patient, the albumin band shifted to the cathode side. The abnormal
precipitin arc of IgA-albumin complexes was detected by immunoelectrophoresis. To
elucidate the mechanism of IgA-albumin complexes, we analyzed their properties
using immunoelectrophoresis, Western blotting, and two-dimensional gel
electrophoresis. The macromolecularized albumin spots were demonstrated by two
dimensional Western blotting with antiserum to human albumin of the patient's
serum. Moreover, the IgA-albumin complexes were dissociated on treatment with 2
mercaptoethanol. It can be considered that albumin is bound to the monoclonal IgA
molecule by covalent disulfide bonds, and that the albumin binding site is
located near the hinge region (311Cys) of the IgA molecule and involves the free
SH group, thought to be present in the alpha-chain.
PMID- 27509725
TI - [Electrophoretic Analysis of Serum Lipoproteins: Its Usefulness and Problems].
AB - Analysis of serum lipoprotein fractions by electrophoresis (lipoprotein
electrophoresis) reveals lipid metabolism disorders, and provides various types
of bio-information which lead to an accurate diagnosis and effective treatment
for dyslipidemia and related diseases (e.g., coronary artery disease or chronic
kidney disease). In particular, lipoprotein electrophoresis enables us to define
the phenotypes of dyslipidemia, and to detect abnormal lipoproteins, which are
potent biomarkers of atherosclerotic disease. In addition, lipoprotein
electrophoresis is an indispensable complement to other assay methods for serum
lipid component measurement that have some limitations, such as a homogeneous
assay for LDL-C. However, it appears to be underestimated regarding its clinical
usefulness. Indeed, the fee for lipoprotein electrophoresis tests is too low.
This review specifically discusses the clinical usefulness and problems of
lipoprotein electrophoresis, with a special emphasis on cost.
PMID- 27509726
TI - [Electrophoretic Analysis of Abnormal Data Discovered by Serum Enzyme Testing].
AB - Lactate dehydrogenase (LD) isozymes are formed by random combinations of two
different subunits encoded by LDHA and LDHB. There are a number of reasons for
unusual LD electrophoretic isozyme patterns. An abnormal electrophoretic pattern
may result from additional LD fractions, altered mobility, an altered molecular
structure, or the distortion of one or more normal bands. The distortion of
normal bands may be caused by immunoglobulin or other protein binding, genetic
variants, or tumor production. The genetic mutations occasionally cause
hereditary deficiency of the LD-A subunit or LD-B subunit, yielding specific LD
isozyme patterns in serum and erythrocytes. Different LD isozyme patterns in
cancer patients possibly originate from changes in expression of LDHA or LDHB due
to other regulatory genes or promoter methylation or from deletions,
duplications, or changes in gene copy numbers. We encountered a patient with
retinoblastoma and a cell line, R51, that showed an LD-1-dominant isozyme
pattern. We found that the abnormal isozyme pattern was mainly due to
transcriptional silencing by aberrant DNA methylation in the promoter region of
the LDHA gene. On the contrary, high LDHA was observed in gastrointestinal
cancer, prostate cancer, and breast cancer tissues according to promoter
hypermethylation of LDHB. The LD isozyme patterns in cancer patients reflect
original tissues or cells regulated by the gene dosage effect or gene expression,
which are both genetically and epigenetically controlled (especially aberrant DNA
methylation).
PMID- 27509727
TI - [Team-Based Clinical Laboratory Testing in Nephrology and Urology--Chairmen's
Introductory Remarks].
AB - Recently, the Department of Clinical Examination has been extensively subdivided.
When we perform examinations, we often require wide knowledge of other
specialized fields. This symposium was planned to consider the procedure for
examinations in the kidney urology field. Seven professionals gave lectures on
the interpretation and adequacy of examinations involving the kidney urology
field. Knowledge of not only specialized fields but also wide, basic, routine
fields is required to perform more precise examinations. Therefore, we became
aware that cooperation between examination departments is essential to improve
our overall judgments.
PMID- 27509728
TI - [How Far We can Diagnose by Urine Sediment Tests?].
AB - Morphological examinations for renal disease are mainly renal biopsy and urine
sediment tests. Biopsy specimens are now evaluated in detail, and test items are
evaluated as highly sensitive and specific compared with urine sediments, which
reflect renal changes indirectly and are low in sensitivity and specificity. On
the other hand, the standardization of urine sediment tests is now in progress,
and some labs can provide sediment results beyond screening for distracted RBC,
differential WBC, or atypical cells. The diagnostic importance of sediments is
revisited.
PMID- 27509729
TI - [Consideration of Physiological Examination and Laboratory Testing: Symposium].
AB - It is very effective to combine physiological examination (resistive index by
renal Doppler) and laboratory testing (estimated glomerular filtration rate and
albuminuria) when analyzing diabetic nephropathy associated with metabolic
syndrome. In particular, the resistive index value is important for increasing
diagnostic capabilities. We expect renal blood flow measurement using Sonazoid to
increase accuracy.
PMID- 27509730
TI - [Overview of Clinical Examination in Nephrology and Urology--Efficacy of Routine
Ultrasound in Detection of Chronic Kidney Disease].
AB - PURPOSE: We re-evaluated the usefulness of ultrasound (US) performed in routine
examination as a screening procedure for chronic kidney disease. PATIENTS AND
METHODS: Of 294 patients screened by US in routine examination, 75 were
identified as those with chronic renal damage during a one-month period (March
2013) in our hospital. We examined the patients' clinical background and
extracted their characteristics. RESULTS: Thirty-six patients with chronic renal
damage were detected out of US in 72 suspected cases, and 39 in 222 unsuspected
cases. Among the latter group, US was performed to examine the upper abdomen in
35 cases, and to examine the whole abdomen in 3 cases. Among the latter group, US
was performed in a checkup of the liver in 14 cases, as a routine examination for
diabetics in 7 cases, and as a screening test for cancer in 4 cases. Among the
latter group, US was performed on the request of endocrinologists in 12 cases,
surgeons in 6 cases, and cardiovascular teams in 6 cases. CONCLUSION: Many
patients with chronic kidney disease were detected by US in unsuspected cases
incidentally. In other words, we should note that their physicians often did not
intend to look for it at the time of ordering US examination. US may be useful
for the detection of chronic kidney disease not only in high-risk cases, but also
in low-risk, unsuspected cases.
PMID- 27509731
TI - [Management of Personal Information in Clinical Laboratory Medicine:--Chairmen's
Introductory Remarks].
AB - The Japanese Society of Laboratory Medicine has been running its own Medical
Safety Committee, and holding a symposium on medical safety during the annual
meeting. The medical world is filled with a considerable amount of personal
information, including genetic information, the ultimate personal information.
We, as medical staff, have to manage such personal information not only in times
of peace but also during disasters or emergency situations. In Japan, the Act on
the Protection of Personal Information is currently being implemented, but a
number of problems remain. Human beings have entered the information technology
era, including electrical medical record systems, which is useful for research
and education besides medical practice. This is why personal information must be
more effectively protected from leakage, misconception, and abuse. We should
create a sound system to manage personal information, with the spirit of
protecting patient information that originated from the Oath of Hippocrates.
PMID- 27509732
TI - [Security Management in Clinical Laboratory Departments and Facilities: Current
Status and Issues].
AB - We conducted a questionnaire survey regarding the current activities for
protecting patients' privacy and the security of information systems (IS) related
to the clinical laboratory departments of university hospitals, certified
training facilities for clinical laboratories, and general hospitals in Yamaguchi
Prefecture. The response rate was 47% from 215 medical institutions, including
three commercial clinical laboratory centers. The results showed that there were
some differences in management activities among facilities with respect to
continuing education, the documentation or regulation of operational management
for paper records, electronic information, remaining samples, genetic testing,
and laboratory information for secondary use. They were suggested to be caused by
differences in functions between university and general hospitals, differences in
the scale of hospitals, or whether or not hospitals have received accreditation
or ISO 15189. Regarding the IS, although the majority of facilities had
sufficiently employed the access control to IS, there was some room for
improvement in the management of special cases such as VIPs and patients with HIV
infection. Furthermore, there were issues regarding the login method for
computers shared by multiple staff, the showing of the names of personnel in
charge of reports, and the risks associated with direct connections to systems
and the Internet and the use of portable media such as USB memory sticks. These
results indicated that further efforts are necessary for each facility to
continue self-assessment and make improvements.
PMID- 27509733
TI - [Requirements for Dealing with Personal Genetic Information in Clinical
Practice].
AB - As clinical genetics evolves, we must deal with a considerable amount of genetic
information in clinical practice. In this review, I mention important
requirements for dealing with personal genetic information in medical care.
Firstly, quality assurance of molecular genetic testing is required for quality
assurance of genetic information. As most labs. have developed "home brew" tests
without analytical and clinical validity, the standardization or automation of
genetic tests should be developed. If not, it is recommended that genetic tests
are performed with the "Best Practice Guideline". Secondly, the confidentiality
of genetic information is required because genetic information may be highly
predictive of the future health of an individual and have important implications
for the relatives of the person tested. For the same reasons, genetic counseling
is required following genetic tests. Finally, genetic test results have to be
interpreted and a report compiled, which must be easy to understand for
physicians and clients. The number of genome bioinformaticians is very limited in
Japan, and more must be immediately trained. On dealing with personal genetic
information in clinical practice, many issues still remain, and each issue should
be steadily resolved.
PMID- 27509734
TI - [Management System of Personal Data Protection in the Health Care Field].
AB - In Japan, the law on personal data protection was enacted in 2005. Privacy is a
human right, including the 1981 right to be let alone. The need for
confidentiality in the health care field has been accepted since the ancient
Greek era, and privacy in the 19th century was developed in this field. However,
the concept of privacy has gradually altered, especially due to the development
of information technology. The author suggests that the guideline for the
security of heath information systems of the Ministry of Health, Labour, and
Welfare is very important and information security management with PDCA cycles is
essential for personal data protection in the health care field. In recent years,
gathering a large amount of life logging or health-related data and analyzing
such data for academic and/or industrial applications has become common. Revising
privacy protection legislation has become an urgent political issue in many
countries. The Japanese Government published their policy to personal data
protection act in Dec. 2013. Balancing public benefit and privacy is a major task
of future legislation. The author recommends that health care professionals pay
attention to, participate in the discussion of, and make suggestions regarding
this act.
PMID- 27509735
TI - [Laboratory Medicine and Medical Team Approaches--Opening Remarks from the
Chair].
AB - Recently, medical team approaches were pointed out to be important in the field
of laboratory medicine. The staff working in laboratory medicine needs to
participate in various kinds of medical team such as ICT or NST. With such a
background, the working group for medical teams was established in the Japanese
Society of Laboratory Medicine in January 2012. Special program II was organized
by this group at the 60th annual meeting held in Kobe in 2013. People gathered
from representative societies related to laboratory medicine and discussed how we
should participate in team approaches. Based on the results of meaningful
discussions, we have reached a strong consensus to pursue team approaches in the
future.
PMID- 27509736
TI - [Nutrition Support as Team Medical Care].
AB - Nutrition support is important to prevent complicating disorders such as
infections and decubitus and to improve patient outcomes. The nutrition support
team (NST), which is usually composed of a physician, nurse, nutritionist,
clinical laboratory technician, pharmacist, and office worker, is effective for
preventing complications and reducing costs for hospitalized patients. To screen
for malnutrition in an early phase, biochemical markers are useful. Transthyretin
(TTR) is a serum protein synthesized mainly by the liver. TTR has a short half
life in the bloodstream of 2 days, and is often used as a rapid and sensitive
marker of malnutrition. However, TTR also decreases under inflammatory and
infectious conditions. We recently established the Kumamoto Index to assess both
the inflammatory and nutritional state of patients.
PMID- 27509737
TI - [From JSLH (The Japanese Society for Laboratory Hematology): An Active Team
Approach to Medicine as Laboratory Technologists, through Showing Bone Marrow and
Peripheral Blood Samples Directly to Patients with Hematological Malignancy].
AB - The clinical path for the treatment of acute myeloid leukemia (AML) patients has
been in practice in our hospital since 2003. In the clinical path, laboratory
technologists take on the role of explaining the microscopic findings in bone
marrow and peripheral blood samples to patients (with or without their families)
using the view-sharing microscope in our laboratory. From July 2003 to October
2014, 56 patients were enrolled in the AML clinical path and given an explanation
of their bone marrow and peripheral blood samples. The patients' median age was
62, and the median time spent for explanation was 40 minutes. We conducted a
questionnaire feedback survey involving those who enrolled, and the results
showed significant improvement in the recognition of the disease pathophysiology,
treatment efficacy, and the importance of precautions against infectious
diseases. Based on the feedback, we have made marked efforts to provide patients
with an improved environment during the explanatory session. This includes
installing a special display for the patients, drawing a schematic illustration
that shows how the blood cells differentiate, and putting them into operation in
a hematology ward to promote patient privacy and precautions against infectious
diseases. Hematological laboratory technologists have played an important role in
patient care in our hospital. To perform their role as effectively as possible,
hematological laboratory technologists participate in the conferences of the
Department of Hematology and Oncology regularly, in which medical staff members
can discuss the conditions and clinical courses of patients. We aim to contribute
to patient satisfaction by sophisticating specialized knowledge as hematological
laboratory technologists and cooperate with other medical staff members.
PMID- 27509738
TI - [Laboratory and Team-Based Medicine--From the Standpoint of JSLM].
AB - The Japanese Society of Laboratory Medicine (JSLM) organized a working group to
promote team-based medicine 2 years ago. The Japan Society for Clinical
Laboratory Automation (JSCLA) formed a committee for team-based medicine and it
was active for five years from 2006 to 2011. The author, an officer of the JSCLA,
presents previous activities and policies for the future. The three main
activities were as follows: Firstly, a seminar with a lecture and practice was
held at meetings of the JSCLA. Secondly, Internet services were set up to
introduce action programs and promote team-based medicine. Thirdly, the guidebook
was edited, written from the point of view of laboratory medicine. The committee
worked hard and produced favorable results. It is difficult with the present
circumstances to organize a committee for team-based medicine in the JSCLA again.
We expect cooperation in seminars and meetings.
PMID- 27509739
TI - [Japanese Association of Clinical Laborato Physicians--What We Are Doing Now and
How We Should Develop in the Future as Competent Members of Team Medicine].
AB - No clinical laboratory would admit they do not practice team medicine, at least
conceptually. However, true team medicine is more than an aspiration--it is an
intentional care structure built, led, and delivered by a diverse,
multidisciplinary team of physicians, medical technologists, nurses, pharmacists,
and dozens of other professionals. We clinical laboratory physicians are able to
fulfill an important role as competent members of the team medicine. Because we
can look at the results of clinical examinations of patients earlier than anyone
else, we can interpret the patient's condition by analyzing that results, and
provide useful information to facilitate team medicine. I have conducted a
questionnaire survey on team medicine targeting clinical laboratory physicians to
clarify the tasks we are performing. In this paper, I describe what clinical
laboratory physicians are currently doing, and how should we develop in the
future.
PMID- 27509740
TI - [Coordination and Role-Sharing between Health Care Professionals].
AB - In recent years, people's demands for medical services are increasing and,
simultaneously, the overwork of health professionals has been pointed out. It is
important to establish a system with which each medical professional can show
higher levels of expertise and work as a team member to provide efficient and
safe medical care. For this reason, a list of medical activities which can be
performed by not only doctors but also other health professionals was devised by
the Director General of the Health Policy Bureau on December 28th, 2007, as the
"Promotion of role-sharing between doctors and other medical professionals,
clerical staff, etc." In August 2009 the "Committee for the Promotion of Team
Approach to Medical Care" was established and it reviewed the situation of
collaboration and cooperation with doctors and other medical professionals. In
the report "Promotion of Team Approach to Medical Care", which was summarized on
March 19th, 2009, "Team Approach to Medical Care" was defined as "appropriate
medical care provided by various medical professionals by sharing information and
purposes of care while cooperating and complementing each other based on
expertise." In May 2010, the "Promotion Council of Team Approach to Medical Care"
was established to discuss the scope of practice for nurses and other medical
professionals. As a result the council suggested to: 1) Institutionalize a
training system for nurses who provide Specified Acts (a part of Assist in
Medical Care), 2) Reconsider the scope of practice for radiological
technologists, 3) Reconsider the scope of practice for laboratory technicians,
and 4) Reconsider the implementation system for dental hygienists. We realized
these policies in June 2014.
PMID- 27509741
TI - Tracking wild sockeye salmon smolts to the ocean reveals distinct regions of
nocturnal movement and high mortality.
AB - Few estimates of migration rates or descriptions of behavior or survival exist
for wild populations of out-migrating Pacific salmon smolts from natal freshwater
rearing areas to the ocean. Using acoustic transmitters and fixed receiver arrays
across four years (2010-2013), we tracked the migration of > 1850 wild sockeye
salmon (Oncorhynchus nerka) smolts from Chilko Lake, British Columbia, to the
coastal Pacific Ocean (> 1000 km distance). Cumulative survival to the ocean
ranged 3-10% among years, although this may be slightly underestimated due to
technical limitations at the final receiver array. Distinct spatial patterns in
both behavior and survival were observed through all years. In small, clear,
upper-river reaches, downstream migration largely occurred at night at speeds up
to 50 km/d and coincided with poor survival. Among years, only 57-78% of smolts
survived the first 80 km. Parallel laboratory experiments revealed excellent
short-term survival and unhindered swimming performance of dummy-tagged smolts,
suggesting that predators rather than tagging effects were responsible for the
initial high mortality of acoustic-tagged smolts. Migration speeds increased in
the Fraser River mainstem (~220 km/d in some years), diel movement patterns
ceased, and smolt survival generally exceeded 90% in this segment. Marine
movement rates and survival were variable across years, with among-year segment
specific survival being the most variable and lowest (19-61%) during the final
(and longest, 240 km) marine migration segment. Osmoregulatory preparedness was
not expected to influence marine survival, as smolts could maintain normal levels
of plasma chloride when experimentally exposed to saltwater (30 ppt) immediately
upon commencing their migration from Chilko Lake. Transportation of smolts
downstream generally increased survival to the farthest marine array. The act of
tagging may have affected smolts in the marine environment in some years as dummy
tagged fish had poorer survival than control fish when transitioned to saltwater
in laboratory-based experiments. Current fisheries models for forecasting the
number of adult sockeye returning to spawn have been inaccurate in recent years
and generally do not incorporate juvenile or smolt survival information. Our
results highlight significant potential for early migration conditions to
influence adult recruitment.
PMID- 27509742
TI - Assessing reproductive behavior important to fisheries management: a case study
with red drum, Sciaenops ocellatus.
AB - Spawning site selection and reproductive timing affect stock productivity and
structure in marine fishes but are poorly understood. Traditionally, stock
assessments measure reproductive potential as spawning stock biomass or egg
production and do not include other aspects of reproductive behavior. Red drum
make an excellent case study to assess these other aspects, as (1) they are
highly fecund, pelagic spawners, like most exploited marine fishes; (2) their
life cycle is delineated between nursery (estuarine) and adult (coastal and
offshore) habitat; and (3) they are managed at these two spatial scales. This
study was conducted from August 2012 to December 2013 and integrates data from
multiple methods and spatial scales. Aerial surveys were used for large-scale
monitoring of aggregations off two known estuarine nursery areas, Tampa Bay and
Charlotte Harbor, Florida, USA. Capture-based sampling in Tampa Bay coastal (n =
2581) and estuarine waters (n = 158) was used to assess reproductive state and to
confirm coastal spawning. To assess spatial dynamics, we acoustically tagged two
population components in the Tampa Bay system, subadults from the estuary (n =
20) and adults from the coastal spawning site (n = 60). Behavioral plasticity was
seen in subadult recruitment to coastal habitat, with some subadults maturing and
recruiting before or during the spawning season and others (14 of 20 acoustically
tagged fish) recruiting at the end of the 2012 spawning season. Both adults and
recruited subadults (n = 29) were consequently detected in the Charlotte Harbor
array, 132 km to the south. Spawning-site fidelity to the Tampa Bay spawning site
occurred at both the population and individual scales. Aggregations consistently
occurred in Tampa Bay coastal waters during the spawning season, and
approximately two-thirds of tagged adults returned in the 2013 spawning season. A
similar proportion of subadults returned to the Tampa Bay spawning site,
exhibiting natal homing. However, these first-time spawners arrived later than
repeat spawners and were detected over shorter time periods. This study, and
others like it, demonstrates how integrating data from individuals tracked over
space and time with more traditional population-based sampling is changing our
understanding of ecological processes that affect marine fish productivity and
our ability to manage for sustainablity.
PMID- 27509743
TI - Cascading effects of fire retardant on plant-microbe interactions, community
composition, and invasion.
AB - Climate change, historical fire suppression, and a rise in human movements in
urban-forest boundaries have resulted in an increased use of long-term fire
retardant (LTFR). While LTFR is an effective fire-fighting tool, it contains high
concentrations of nitrogen and phosphorus, and little is known about how this
nutrient pulse affects terrestrial ecosystems. We used field surveys and
greenhouse experiments to quantify effects of LTFR on plant productivity,
community composition, and plant interactions with the ubiquitous root symbiont
arbuscular mycorrhizal fungi (AMF). In the field, LTFR applications were
associated with persistent shifts in plant communities toward exotic annuals with
little or no dependency of AMF. Plants exposed to LTFR were less colonized by
AMF, both in field surveys and in the greenhouse, and this was most likely due to
the substantial and persistent increase in soil available phosphorus. All plants
grew bigger with LTFR in the greenhouse, but the invasive annual cheatgrass
(Bromus tectorum) benefitted most. While LTFR can control fires, it may cause
long-term changes in soil nutrient availabilities, disrupt plant interactions
with beneficial soil microbes, and exasperate invasion by some exotic plants.
PMID- 27509744
TI - Adaptation services of floodplains and wetlands under transformational climate
change.
AB - Adaptation services are the ecosystem processes and services that benefit people
by increasing their ability to adapt to change. Benefits may accrue from existing
but newly used services where ecosystems persist or from novel services supplied
following ecosystem transformation. Ecosystem properties that enable persistence
or transformation are important adaptation services because they support future
options. The adaptation services approach can be applied to decisions on trade
offs between currently valued services and benefits from maintaining future
options. For example, ecosystem functions and services of floodplains depend on
river flows. In those regions of the world where climate change projections are
for hotter, drier conditions, floods will be less frequent and floodplains will
either persist, though with modified structure and function, or transform to
terrestrial (flood-independent) ecosystems. Many currently valued ecosystem
services will reduce in supply or become unavailable, but new options are
provided by adaptation services. We present a case study from the Murray-Darling
Basin, Australia, for operationalizing the adaptation services concept for
floodplains and wetlands. We found large changes in flow and flood regimes are
likely under a scenario of +1.6 degrees C by 2030, even with additional water
restored to rivers under the proposed Murray-Darling Basin Plan. We predict major
changes to floodplain ecosystems, including contraction of riparian forests and
woodlands and expansion of terrestrial, drought-tolerant vegetation communities.
Examples of adaptation services under this scenario include substitution of
irrigated agriculture with dryland cropping and floodplain grazing; mitigation of
damage from rarer, extreme floods; and increased tourism, recreational, and
cultural values derived from fewer, smaller wetlands that can be maintained with
environmental flows. Management for adaptation services will require decisions on
where intervention can enable ecosystem persistence and where transformation is
inevitable. New ways of managing water that include consideration of the
increasing importance of adaptation services requires major changes to decision
making that better account for landscape heterogeneity and large-scale change
rather than attempting to maintain ecosystems in fixed states.
PMID- 27509745
TI - Prioritizing land management efforts at a landscape scale: a case study using
prescribed fire in Wisconsin.
AB - One challenge in the effort to conserve biodiversity is identifying where to
prioritize resources for active land management. Cost-benefit analyses have been
used successfully as a conservation tool to identify sites that provide the
greatest conservation benefit per unit cost. Our goal was to apply cost-benefit
analysis to the question of how to prioritize land management efforts, in our
case the application of prescribed fire to natural landscapes in Wisconsin, USA.
We quantified and mapped frequently burned communities and prioritized management
units based on a suite of indices that captured ecological benefits, management
effort, and the feasibility of successful long-term management actions. Data for
these indices came from LANDFIRE, Wisconsin's Wildlife Action Plan, and a
nationwide wildland-urban interface assessment. We found that the majority of
frequently burned vegetation types occurred in the southern portion of the state.
However, the highest priority areas for applying prescribed fire occurred in the
central, northwest, and northeast portion of the state where frequently burned
vegetation patches were larger and where identified areas of high biological
importance area occurred. Although our focus was on the use of prescribed fire in
Wisconsin, our methods can be adapted to prioritize other land management
activities. Such prioritization is necessary to achieve the greatest possible
benefits from limited funding for land management actions, and our results show
that it is feasible at scales that are relevant for land management decisions.
PMID- 27509746
TI - A fire history derived from Pinus resinosa Ait. for the Islands of Eastern Lac La
Croix, Minnesota, USA.
AB - We reconstructed fire occurrence near a fur-trade era canoe travel corridor (used
ca. 1780-1802) in the Quetico-Superior region west of Lake Superior to explore
the possibility of human influence on pre-fire suppression rates of fire
occurrence. Our research objectives were to (1) examine the spatial and temporal
patterns of fire in the study area, (2) test fires' strength of association with
regional drought, and (3) assess whether reconstructed fire frequencies could be
explained by observed rates of lightning fire ignition over the modern period of
record. We developed a 420-year fire history for the eastern portion of Lac La
Croix in the Boundary Waters Canoe Area Wilderness (BWCAW). Seventy-one fire
scarred samples were collected from remnant Pinus resinosa Ait. (red pine) stumps
and logs from thirteen distinct island and three mainland forest stands.
Collectively these samples contained records of 255 individual fire scars
representing 79 fire events from 1636 to 1933 (study area mean fire intervals
[MFI] 3.8 yr). Reconstructed fires were spatially and temporally asynchronous and
not strongly associated with regional drought (P > 0.05). When compared to the
conservative, tree-ring reconstructed estimate of historical fire occurrence and
modern lightning-caused fires (1929-2012), a noticeable change in the
distribution and frequency of fires within the study area was evident with only
two lightning-ignited island fires since 1934 in the study area. Our results
suggest a high likelihood that indigenous land use contributed to surface fire
ignitions within our study area and highlights the importance of examining the
potential effects of past indigenous land use when determining modern approaches
to fire and wilderness management in fire-adapted ecosystems.
PMID- 27509747
TI - Competitive release and outbreaks of non-target pests associated with transgenic
Bt cotton.
AB - The adoption of transgenic Bt cotton has, in some cases, led to environmental and
economic benefits through reduced insecticide use. However, the distribution of
these benefits and associated risks among cotton growers and cotton-growing
regions has been uneven due in part to outbreaks of non-target or secondary
pests, thereby requiring the continued use of synthetic insecticides. In the
southeastern USA, Bt cotton adoption has resulted in increased abundance of and
damage from stink bug pests, Euschistus servus and Nezara viridula (Heteroptera:
Pentatomidae). While the impact of increased stink bug abundance has been well
documented, the causes have remained unclear. We hypothesize that release from
competition with Bt-susceptible target pests may drive stink bug outbreaks in Bt
cotton. We first examined the evidence for competitive release of stink bugs
through meta-analysis of previous studies. We then experimentally tested if
herbivory by Bt-susceptible Helicoverpa zea increases stink bug leaving rates and
deters oviposition on non-Bt cotton. Consistent with previous studies, we found
differences in leaving rates only for E servus, but we found that both species
strongly avoided ovipositing on H. zea-damaged plants. Considering all available
evidence, competitive release of stink bug populations in Bt cotton likely
contributes to outbreaks, though the relative importance of competitive release
remains an open question. Ecological risk assessments of Bt crops and other
transgenic insecticidal crops would benefit from greater understanding of the
ecological mechanisms underlying non-target pest outbreaks and greater attention
to indirect ecological effects more broadly.
PMID- 27509748
TI - The cost and feasibility of marine coastal restoration.
AB - Land-use change in the coastal zone has led to worldwide degradation of marine
coastal ecosystems and a loss of the goods and services they provide. Restoration
is the process of assisting the recovery of an ecosystem that has been degraded,
damaged, or destroyed and is critical for habitats where natural recovery is
hindered. Uncertainties about restoration cost and feasibility can impede
decisions on whether, what, how, where, and how much to restore. Here, we perform
a synthesis of 235 studies with 954 observations from restoration or
rehabilitation projects of coral reefs, seagrass, mangroves, salt-marshes, and
oyster reefs worldwide, and evaluate cost, survival of restored organisms,
project duration, area, and techniques applied. Findings showed that while the
median and average reported costs for restoration of one hectare of marine
coastal habitat were around US$80000 (2010) and US$1600000 (2010), respectively,
the real total costs (median) are likely to be two to four times higher. Coral
reefs and seagrass were among the most expensive ecosystems to restore. Mangrove
restoration projects were typically the largest and the least expensive per
hectare. Most marine coastal restoration projects were conducted in Australia,
Europe, and USA, while total restoration costs were significantly (up to 30
times) cheaper in countries with developing economies. Community- or volunteer
based marine restoration projects usually have lower costs. Median survival of
restored marine and coastal organisms, often assessed only within the first one
to two years after restoration, was highest for saltmarshes (64.8%) and coral
reefs (64.5%) and lowest for seagrass (38.0%). However, success rates reported in
the scientific literature could be biased towards publishing successes rather
than failures. The majority of restoration projects were short-lived and seldom
reported monitoring costs. Restoration success depended primarily on the
ecosystem, site selection, and techniques applied rather than on money spent. We
need enhanced investment in both improving restoration practices and large-scale
restoration.
PMID- 27509749
TI - Prey-mediated behavioral responses of feeding blue whales in controlled sound
exposure experiments.
AB - Behavioral response studies provide significant insights into the nature,
magnitude, and consequences of changes in animal behavior in response to some
external stimulus. Controlled exposure experiments (CEEs) to study behavioral
response have faced challenges in quantifying the importance of and interaction
among individual variability, exposure conditions, and environmental covariates.
To investigate these complex parameters relative to blue whale behavior and how
it may change as a function of certain sounds, we deployed multi-sensor acoustic
tags and conducted CEEs using simulated mid-frequency active sonar (MFAS) and
pseudo-random noise (PRN) stimuli, while collecting synoptic, quantitative prey
measures. In contrast to previous approaches that lacked such prey data, our
integrated approach explained substantially more variance in blue whale dive
behavioral responses to mid-frequency sounds (r2 = 0.725 vs. 0.14 previously).
Results demonstrate that deep-feeding whales respond more clearly and strongly to
CEEs than those in other behavioral states, but this was only evident with the
increased explanatory power provided by incorporating prey density and
distribution as contextual covariates. Including contextual variables increases
the ability to characterize behavioral variability and empirically strengthens
previous findings that deep-feeding blue whales respond significantly to mid
frequency sound exposure. However, our results are only based on a single
behavioral state with a limited sample size, and this analytical framework should
be applied broadly across behavioral states. The increased capability to describe
and account for individual response variability by including environmental
variables, such as prey, that drive foraging behavior underscores the importance
of integrating these and other relevant contextual parameters in experimental
designs. Our results suggest the need to measure and account for the ecological
dynamics of predator-prey interactions when studying the effects of anthropogenic
disturbance in feeding animals.
PMID- 27509750
TI - Supply-demand equilibria and the size-number trade-off in spatially structured
recreational fisheries.
AB - Recreational fishing effort varies across complex inland landscapes (e.g., lake
districts) and appears influenced by both angler preferences and qualities of the
fishery resource, like fish size and abundance. However, fish size and abundance
have an ecological trade-off within a population, thereby structuring equal
quality isopleths expressing this trade-off across the fishing landscape. Since
expressed preferences of recreational anglers (i.e., site-selection of high
quality fishing opportunities among many lakes) can be analogous to optimal
foraging strategies of natural predators, adopting such concepts can aid in
understanding scale-dependence in fish-angler interactions and impacts of fishing
across broad landscapes. Here, we assumed a fish supply-angler demand equilibria
and adapted a novel bivariate measure of fishing quality based on fish size and
catch rates to assess how recreational anglers influence fishing quality among a
complex inland landscape. We then applied this metric to evaluate (1) angler
preferences for caught and released fish compared to harvested fish, (2) the
nonlinear size-numbers trade-off with uncertainty in both traits, and (3) the
spatial-scale of the equilibria across 62 lakes and four independent management
regions in British Columbia's (BC) rainbow trout Oncorhynchus mykiss fishery. We
found anglers had low preference for caught and released fish (~10% of the value
compared to harvested fish), which modified anglers' perception of fishing
quality. Hence, fishing quality and angler effort was not influenced simply by
total fish caught, but largely by harvested fish catch rates. Fishing quality
varied from BC's northern regions (larger fish and more abundant) compared to
southern regions (smaller fish and less abundant) directly associated with a 2.5
times increase in annual fishing effort in southern regions, suggesting that
latent fishing pressure can structure the size-numbers trade-off in rainbow trout
populations. The presence of two different equal-quality isopleths suggests at
least two effective landscapes support co-occurring ideal free distributions of
recreational fishing effort in BC's rainbow fishery. Anglers' expressed
preferences among lakes interacted with density dependent growth and survival
within lakes to structure a size-numbers trade-off influencing how anglers
perceive fishing quality and, ultimately, distribute across complex inland
landscapes.
PMID- 27509751
TI - Limited carbon and biodiversity co-benefits for tropical forest mammals and
birds.
AB - The conservation of tropical forest carbon stocks offers the opportunity to curb
climate change by reducing greenhouse gas emissions from deforestation and
simultaneously conserve biodiversity. However, there has been considerable debate
about the extent to which carbon stock conservation will provide benefits to
biodiversity in part because whether forests that contain high carbon density in
their aboveground biomass also contain high animal diversity is unknown. Here, we
empirically examined medium to large bodied ground-dwelling mammal and bird
(hereafter "wildlife") diversity and carbon stock levels within the tropics using
camera trap and vegetation data from a pantropical network of sites.
Specifically, we tested whether tropical forests that stored more carbon
contained higher wildlife species richness, taxonomic diversity, and trait
diversity. We found that carbon stocks were not a significant predictor for any
of these three measures of diversity, which suggests that benefits for wildlife
diversity will not be maximized unless wildlife diversity is explicitly taken
into account; prioritizing carbon stocks alone will not necessarily meet
biodiversity conservation goals. We recommend conservation planning that
considers both objectives because there is the potential for more wildlife
diversity and carbon stock conservation to be achieved for the same total budget
if both objectives are pursued in tandem rather than independently. Tropical
forests with low elevation variability and low tree density supported
significantly higher wildlife diversity. These tropical forest characteristics
may provide more affordable proxies of wildlife diversity for future multi
objective conservation planning when fine scale data on wildlife are lacking.
PMID- 27509752
TI - Assessing the umbrella value of a range-wide conservation network for jaguars
(Panthera onca).
AB - Umbrella species are employed as conservation short-cuts for the design of
reserves or reserve networks. However, empirical data on the effectiveness of
umbrellas is equivocal, which has prevented more widespread application of this
conservation strategy. We perform a novel, large-scale evaluation of umbrella
species by assessing the potential umbrella value of a jaguar (Panthera onca)
conservation network (consisting of viable populations and corridors) that
extends from Mexico to Argentina. Using species richness, habitat quality, and
fragmentation indices of ~1500 co-occurring mammal species, we show that jaguar
populations and corridors overlap a substantial amount and percentage of high
quality habitat for co-occurring mammals and that the jaguar network performs
better than random networks in protecting high-quality, interior habitat.
Significantly, the effectiveness of the jaguar network as an umbrella would not
have been noticeable had we focused on species richness as our sole metric of
umbrella utility. Substantial inter-order variability existed, indicating the
need for complementary conservation strategies for certain groups of mammals. We
offer several reasons for the positive result we document, including the large
spatial scale of our analysis and our focus on multiple metrics of umbrella
effectiveness. Taken together, our results demonstrate that a regional, single
species conservation strategy can serve as an effective umbrella for the larger
community and should help conserve viable populations and connectivity for a
suite of co-occurring mammals. Current and future range-wide planning exercises
for other large predators may therefore have important umbrella benefits.
PMID- 27509753
TI - Estimating population density and connectivity of American mink using spatial
capture-recapture.
AB - Estimating the abundance or density of populations is fundamental to the
conservation and management of species, and as landscapes become more fragmented,
maintaining landscape connectivity has become one of the most important
challenges for biodiversity conservation. Yet these two issues have never been
formally integrated together in a model that simultaneously models abundance
while accounting for connectivity of a landscape. We demonstrate an application
of using capture-recapture to develop a model of animal density using a least
cost path model for individual encounter probability that accounts for non
Euclidean connectivity in a highly structured network. We utilized scat detection
dogs (Canis lupus familiaris) as a means of collecting non-invasive genetic
samples of American mink (Neovison vison) individuals and used spatial capture
recapture models (SCR) to gain inferences about mink population density and
connectivity. Density of mink was not constant across the landscape, but rather
increased with increasing distance from city, town, or village centers, and mink
activity was associated with water. The SCR model allowed us to estimate the
density and spatial distribution of individuals across a 388 km2 area. The model
was used to investigate patterns of space usage and to evaluate covariate effects
on encounter probabilities, including differences between sexes. This study
provides an application of capture-recapture models based on ecological distance,
allowing us to directly estimate landscape connectivity. This approach should be
widely applicable to provide simultaneous direct estimates of density, space
usage, and landscape connectivity for many species.
PMID- 27509754
TI - A generalizable energetics-based model of avian migration to facilitate
continental-scale waterbird conservation.
AB - Conserving migratory birds is made especially difficult because of movement among
spatially disparate locations across the annual cycle. In light of challenges
presented by the scale and ecology of migratory birds, successful conservation
requires integrating objectives, management, and monitoring across scales, from
local management units to ecoregional and flyway administrative boundaries. We
present an integrated approach using a spatially explicit energetic-based
mechanistic bird migration model useful to conservation decision-making across
disparate scales and locations. This model moves a Mallard-like bird (Anas
platyrhynchos), through spring and fall migration as a function of caloric gains
and losses across a continental-scale energy landscape. We predicted with this
model that fall migration, where birds moved from breeding to wintering habitat,
took a mean of 27.5 d of flight with a mean seasonal survivorship of 90.5% (95%
Cl = 89.2%, 91.9%), whereas spring migration took a mean of 23.5 d of flight with
mean seasonal survivorship of 93.6% (95% CI = 92.5%, 94.7%). Sensitivity analyses
suggested that survival during migration was sensitive to flight speed, flight
cost, the amount of energy the animal could carry, and the spatial pattern of
energy availability, but generally insensitive to total energy availability per
se. Nevertheless, continental patterns in the bird-use days occurred principally
in relation to wetland cover and agricultural habitat in the fall. Bird-use days
were highest in both spring and fall in the Mississippi Alluvial Valley and along
the coast and near-shore environments of South Carolina. Spatial sensitivity
analyses suggested that locations nearer to migratory endpoints were less
important to survivorship; for instance, removing energy from a 1036 km2 stopover
site at a time from the Atlantic Flyway suggested coastal areas between New
Jersey and North Carolina, including the Chesapeake Bay and the North Carolina
piedmont, are essential locations for efficient migration and increasing
survivorship during spring migration but not locations in Ontario and
Massachusetts. This sort of spatially explicit information may allow decision
makers to prioritize their conservation actions toward locations most influential
to migratory success. Thus, this mechanistic model of avian migration provides a
decision-analytic medium integrating the potential consequences of local actions
to flyway-scale phenomena.
PMID- 27509755
TI - Addressing potential local adaptation in species distribution models:
implications for conservation under climate change.
AB - Species distribution models (SDMs) have been criticized for involving assumptions
that ignore or categorize many ecologically relevant factors such as dispersal
ability and biotic interactions. Another potential source of model error is the
assumption that species are ecologically uniform in their climatic tolerances
across their range. Typically, SDMs treat a species as a single entity, although
populations of many species differ due to local adaptation or other genetic
differentiation. Not taking local adaptation into account may lead to incorrect
range prediction and therefore misplaced conservation efforts. A constraint is
that we often do not know the degree to which populations are locally adapted.
Lacking experimental evidence, we still can evaluate niche differentiation within
a species' range to promote better conservation decisions. We explore possible
conservation implications of making type I or type II errors in this context. For
each of two species, we construct three separate Max-Ent models, one considering
the species as a single population and two of disjunct populations. Principal
component analyses and response curves indicate different climate characteristics
in the current environments of the populations. Model projections into future
climates indicate minimal overlap between areas predicted to be climatically
suitable by the whole species vs. population-based models. We present a workflow
for addressing uncertainty surrounding local adaptation in SDM application and
illustrate the value of conducting population-based models to compare with whole
species models. These comparisons might result in more cautious management
actions when alternative range outcomes are considered.
PMID- 27509756
TI - Conservation vs. livelihoods: spatial management of non-timber forest product
harvests in a two-dimensional model.
AB - Areas of high biodiversity often coincide with communities living in extreme
poverty. As a livelihood support, these communities often harvest wild products
from the environment. But harvest activities can have negative impacts on fragile
and globally important ecosystems. This paper examines trade-offs in ecological
protection and community welfare from the harvest of wild products. With a novel
model and empirical evidence, I show that management of harvest activity does not
always resolve these trade-offs. In a model of continuous harvests in a two
dimensional landscape, managed harvest activity improves welfare, but is
uniformly bad for other ecosystem services that are sensitive to the presence (as
opposed to the intensity) of human activity. Empirical results from a unique
dataset of mushroom harvesters in Yunnan, China suggest more experienced, poorer,
and more vulnerable individuals tend to rely on more distant harvests. Thus,
policies that limit the extent of forest travel, such as protected areas, may
protect fragile ecosystems but can have a disproportionately negative effect on
those most vulnerable.
PMID- 27509757
TI - Translocation strategies for multiple species depend on interspecific interaction
type.
AB - Conservation translocations, anthropogenic movements of species to prevent their
extinction, have increased substantially over the last few decades. Although
multiple species are frequently moved to the same location, current translocation
guidelines consider species in isolation. This practice ignores important
interspecific interactions and thereby risks translocation failure. We model
three different two-species systems to illustrate the inherent complexity of
multispecies translocations and to assess the influence of different interaction
types (consumer-resource, mutualism, and competition) on translocation
strategies. We focus on how these different interaction types influence the
optimal founder population sizes for successful translocations and the order in
which the species are moved (simultaneous or sequential). Further, we assess the
effect of interaction strength in simultaneous translocations and the time delay
between translocations when moving two species sequentially. Our results show
that translocation decisions need to reflect the type of interaction. While all
translocations of interacting species require a minimum founder population size,
which is demarked by an extinction boundary, consumer-resource translocations
also have a maximum founder population limit. Above the minimum founder size,
increasing the number of translocated individuals leads to a substantial increase
in the extinction boundary of competitors and consumers, but not of mutualists.
Competitive and consumer-resource systems benefit from sequential translocations,
but the order of translocations does not change the outcomes for mutualistic
interaction partners noticeably. Interspecific interactions are important
processes that shape population dynamics and should therefore be incorporated
into the quantitative planning of multispecies translocations. Our findings apply
whenever interacting species are moved, for example, in reintroductions,
conservation introductions, biological control, or ecosystem restoration.
PMID- 27509758
TI - Projecting pest population dynamics under global warming: the combined effect of
inter- and intra-annual variations.
AB - The typical short generation length of insects makes their population dynamics
highly sensitive not only to mean annual temperatures but also to their intra
annual variations. To consider the combined effect of both thermal factors under
global warming, we propose a modeling framework that links general circulation
models (GCMs) with a stochastic weather generator and population dynamics models
to predict species population responses to inter- and intra-annual temperature
changes. This framework was utilized to explore future changes in populations of
Bemisia tabaci, an invasive insect pest-species that affects multiple
agricultural systems in the Mediterranean region. We considered three locations
representing different pest status and climatic conditions: Montpellier (France),
Seville (Spain), and Beit-Jamal (Israel). We produced ensembles of local daily
temperature realizations representing current and future (mid-21st century)
climatic conditions under two emission scenarios for the three locations. Our
simulations predicted a significant increase in the average number of annual
generations and in population size, and a significant lengthening of the growing
season in all three locations. A negative effect was found only in Seville for
the summer season, where future temperatures lead to a reduction in population
size. High variability in population size was observed between years with similar
annual mean temperatures, suggesting a strong effect of intra-annual temperature
variation. Critical periods were from late spring to late summer in Montpellier
and from late winter to early summer in Seville and Beit-Jamal. Although our
analysis suggested that earlier seasonal activity does not necessarily lead to
increased populations load unless an additional generation is produced, it is
highly likely that the insect will become a significant pest of open-fields at
Mediterranean latitudes above 40 degrees during the next 50 years. Our
simulations also implied that current predictions based on mean temperature
anomalies are relatively conservative and it is better to apply stochastic tools
to resolve complex responses to climate change while taking natural variability
into account. In summary, we propose a modeling framework capable of determining
distinct intra-annual temperature patterns leading to large or small population
sizes, for pest risk assessment and management planning of both natural and
agricultural ecosystems.
PMID- 27509759
TI - Comparison of solar-induced chlorophyll fluorescence, light-use efficiency, and
process-based GPP models in maize.
AB - Accurately quantifying cropland gross primary production (GPP) is of great
importance to monitor cropland status and carbon budgets. Satellite-based light
use efficiency (LUE) models and process-based terrestrial biosphere models (TBMs)
have been widely used to quantify cropland GPP at different scales in past
decades. However, model estimates of GPP are still subject to large
uncertainties, especially for croplands. More recently, space-borne solar-induced
chlorophyll fluorescence (SIF) has shown the ability to monitor photosynthesis
from space, providing new insights into actual photosynthesis monitoring. In this
study, we examined the potential of SIF data to describe maize phenology and
evaluated three GPP modeling approaches (space-borne SIF retrievals, a LUE-based
vegetation photosynthesis model [VPM], and a process-based soil canopy
observation of photochemistry and energy flux [SCOPE] model constrained by SIF)
at a maize (Zea mays L.) site in Mead, Nebraska, USA. The result shows that SIF
captured the seasonal variations (particularly during the early and late growing
season) of tower-derived GPP (GPP_EC) much better than did satellite-based
vegetation indices (enhanced vegetation index [EVI] and land surface water index
[LSWI]). Consequently, SIF was strongly correlated with GPP_EC than were EVI and
LSWI. Evaluation of GPP estimates against GPP_EC during the growing season
demonstrated that all three modeling approaches provided reasonable estimates of
maize GPP, with Pearson's correlation coefficients (r) of 0.97, 0.94, and 0.93
for the SCOPE, VPM, and SIF models, respectively. The SCOPE model provided the
best simulation of maize GPP when SIF observations were incorporated through
optimizing the key parameter of maximum carboxylation capacity (Vcmax). Our
results illustrate the potential of SIF data to offer an additional way to
investigate the seasonality of photosynthetic activity, to constrain process
based models for improving GPP estimates, and to reasonably estimate GPP by
integrating SIF and GPP_EC data without dependency on climate inputs and
satellite-based vegetation indices.
PMID- 27509760
TI - Multiscale connectivity and graph theory highlight critical areas for
conservation under climate change.
AB - Conservation planning and biodiversity management require information on
landscape connectivity across a range of spatial scales from individual home
ranges to large regions. Reduction in landscape connectivity due changes in land
use or development is expected to act synergistically with alterations to habitat
mosaic configuration arising from climate change. We illustrate a multiscale
connectivity framework to aid habitat conservation prioritization in the context
of changing land use and climate. Our approach, which builds upon the strengths
of multiple landscape connectivity methods, including graph theory, circuit
theory, and least-cost path analysis, is here applied to the conservation
planning requirements of the Mohave ground squirrel. The distribution of this
threatened Californian species, as for numerous other desert species, overlaps
with the proposed placement of several utility-scale renewable energy
developments in the American southwest. Our approach uses information derived at
three spatial scales to forecast potential changes in habitat connectivity under
various scenarios of energy development and climate change. By disentangling the
potential effects of habitat loss and fragmentation across multiple scales, we
identify priority conservation areas for both core habitat and critical corridor
or stepping stone habitats. This approach is a first step toward applying graph
theory to analyze habitat connectivity for species with continuously distributed
habitat and should be applicable across a broad range of taxa.
PMID- 27509761
TI - Invasiveness of plant pathogens depends on the spatial scale of host
distribution.
AB - Plant diseases often cause serious yield losses in agriculture. A pathogen's
invasiveness can be quantified by the basic reproductive number, R0. Since
pathogen transmission between host plants depends on the spatial separation
between them, R0 is strongly influenced by the spatial scale of the host
distribution. We present a proof of principle of a novel approach to estimate the
basic reproductivenumber, R0, of plant pathogens as a function of the size of a
field planted with crops and its aspect ratio. This general approach is based on
a spatially explicit population dynamical model. The basic reproductive number
was found to increase with the field size at small field sizes and to saturate to
a constant value at large field sizes. It reaches amaximum in square fields and
decreases as the field becomes elongated. This pattern appears to be quite
general: it holds for dispersal kernels that decrease exponentially or faster, as
well as for fat-tailed dispersal kernels that decrease slower than exponential
(i.e., power-law kernels). We used this approach to estimate R0 in wheat stripe
rust(an important disease caused by Puccinia striiformis), where we inferred both
the transmission rates and the dispersal kernels from the measurements of disease
gradients. For the two largest datasets, we estimated R0 of P. striiformis in the
limit of large fields to be of the order of 30. We found that the spatial extent
over which R0 changes strongly is quite fine-scaled (about 30 m of the linear
extension of the field). Our results indicate that in order to optimize the
spatial scale of deployment of fungicides or host resistances, the adjustments
should be made at a fine spatial scale. We also demonstrated how the knowledge of
the spatial dependence of R0 can improve recommendations with regard to fungicide
treatment.
PMID- 27509762
TI - Evolutionary patterns and physicochemical properties explain macroinvertebrate
sensitivity to heavy metals.
AB - Ecological risk assessment depends strongly on species sensitivity data.
Typically, sensitivity data are based on laboratory toxicity bioassays, which for
practical constraints cannot be exhaustively performed for all species and
chemicals available. Bilinear models integrating phylogenetic information of
species and physicochemical properties of compounds allow to predict species
sensitivity to chemicals. Combining the molecular information (DNA sequences) of
31 invertebrate species with the physicochemical properties of six bivalent
metals, we built bilinear models that explained 70-80% of the variability in
species sensitivity to heavy metals. Phylogeny was the most important component
of the bilinear models, as it explained the major part of the explained variance
(> 40%). Predicted values from bilinear modeling were in agreement with
experimental values (> 50%); therefore, this approach is a good starting point to
build statistical models which can potentially predict heavy metal toxicity for
untested invertebrate species based on empirical values for similar species.
Despite their good performance, development of the presented bilinear models
would benefit from improved phylogenetic and toxicological datasets. Our analysis
is an example for linking evolutionary biology with applied ecotoxicology. Its
future applications may encompass other stress factors or traits influencing the
survival of aquatic organisms in polluted environments.
PMID- 27509763
TI - Rapidly restoring biological soil crusts and ecosystem functions in a severely
disturbed desert ecosystem.
AB - Restoring biological soil crusts (biocrusts) in degraded drylands can contribute
to recovery of ecosystem functions that have global implications, including
erosion resistance and nutrient cycling. To examine techniques for restoring
biocrusts, we conducted a replicated, factorial experiment on recently abandoned
road surfaces by applying biocrust inoculation (salvaged and stored dry for two
years), salvaged topsoil, an abiotic soil amendment (wood shavings), and planting
of a dominant perennial shrub (Ambrosia dumosa). Eighteen months after
treatments, we measured biocrust abundance and species composition, soil
chlorophyll a content and fertility, and soil resistance to erosion. Biocrust
addition significantly accelerated biocrust recovery on disturbed soils,
including increasing lichen and moss cover and cyanobacteria colonization.
Compared to undisturbed controls, inoculated plots had similar lichen and moss
composition, recovered 43% of total cyanobacteria density, had similar soil
chlorophyll content, and exhibited recovery of soil fertility and soil stability.
Inoculation was the only treatment that generated lichen and moss cover. Topsoil
application resulted in partial recovery of the cyanobacteria community and soil
properties. Compared to untreated disturbed plots, topsoil application without
inoculum increased cyanobacteria density by 186% and moderately improved soil
chlorophyll and ammonium content and soil stability. Topsoil application produced
22% and 51% of the cyanobacteria density g-1 soil compared to undisturbed and
inoculated plots, respectively. Plots not treated with either topsoil or inoculum
had significantly lower cyanobacteria density, soil chlorophyll and ammonium
concentrations, and significantly higher soil nitrate concentration. Wood
shavings and Ambrosia had no influence on biocrust lichen and moss species
recovery but did affect cyanobacteria composition and soil fertility. Inoculation
of severely disturbed soil with native biocrusts rapidly restored biocrust
communities and soil stability such that restored areas were similar to
undisturbed desert within three years. Using salvaged biocrust as inoculum can be
an effective tool in ecological restoration because of its efficacy and simple
implementation. Although salvaging biocrust material can be technically difficult
and potentially costly, utilizing opportunities to salvage material in planned
future disturbance can provide additional land management tools.
PMID- 27509764
TI - Ecosystem structure, function, and composition in rangelands are negatively
affected by livestock grazing.
AB - Reports of positive or neutral effects of grazing on plant species richness have
prompted calls for livestock grazing to be used as a tool for managing land for
conservation. Grazing effects, however, are likely to vary among different
response variables, types, and intensity of grazing, and across abiotic
conditions. We aimed to examine how grazing affects ecosystem structure,
function, and composition. We compiled a database of 7615 records reporting an
effect of grazing by sheep and cattle on 278 biotic and abiotic response
variables for published studies across Australia. Using these data, we derived
three ecosystem measures based on structure, function, and composition, which
were compared against six contrasts of grazing pressure, ranging from low to
heavy, two different herbivores (sheep, cattle), and across three different
climatic zones. Grazing reduced structure (by 35%), function (24%), and
composition (10%). Structure and function (but not composition) declined more
when grazed by sheep and cattle together than sheep alone. Grazing reduced plant
biomass (40%), animal richness (15%), and plant and animal abundance, and plant
and litter cover (25%), but had no effect on plant richness nor soil function.
The negative effects of grazing on plant biomass, plant cover, and soil function
were more pronounced in drier environments. Grazing effects on plant and animal
richness and composition were constant, or even declined, with increasing
aridity. Our study represents a comprehensive continental assessment of the
implications of grazing for managing Australian rangelands. Grazing effects were
largely negative, even at very low levels of grazing. Overall, our results
suggest that livestock grazing in Australia is unlikely to produce positive
outcomes for ecosystem structure, function, and composition or even as a blanket
conservation tool unless reduction in specific response variables is an explicit
management objective.
PMID- 27509765
TI - KNOWLEDGE AND SKILLS ENHANCEMENT THROUGH PERIOPERATIVE NURSING SIMULATION LAB
TRAINING.
AB - In Edmonton Zone, the attrition rate among new perioperative nursing staff is an
issue of concern and many ORs are facing noticeable staffing challenges. In the
Edmonton area there are approximately 79 surgical suites. A series of simulation
labs were established in 2015 to provide perioperative nurses in order to
increase their comfort on the job and to help build confidence levels. The
expectations for this simulation are an overall improvement in perioperative
nurses' competency, a reduction in OR orientation and training time, and a
decrease in the attrition rates among OR nurses.
PMID- 27509766
TI - SPOTLIGHT ON ORNAC MEMBERS. AN INTERVIEW WITH ELIZABETH BECK RN, CPN(C), ORNAC
TREASURER.
PMID- 27509767
TI - TRADITIONAL CANISTER-BASED OPEN WASTE MANAGEMENT SYSTEM VERSUS CLOSED SYSTEM:
HAZARDOUS EXPOSURE PREVENTION AND OPERATING THEATRE STAFF SATISFACTION.
AB - INTRODUCTION: Exposure to blood and body fluids is a major concern to health care
professionals working in operating rooms (ORs). Thus, it is essential that
hospitals use fluid waste management systems that minimise risk to staff, while
maximising efficiency. METHOD: The current study compared the utility of a
'closed' system with a traditional canister-based 'open' system in the OR in a
private hospital setting. RESULTS: A total of 30 arthroscopy, urology, and
orthopaedic cases were observed. The closed system was used in five, four, and
six cases, respectively and the open system was used in nine, two, and four
cases, respectively. The average number of opportunities for staff to be exposed
to hazardous fluids were fewer for the closed system when compared to the open
during arthroscopy and urology procedures. The open system required nearly 3.5
times as much staff time for set-up, maintenance during procedures, and post
procedure disposal of waste. Theatre staff expressed greater satisfaction with
the closed system than with the open. CONCLUSION: In conclusion, compared with
the open system, the closed system offers a less hazardous and more efficient
method of disposing of fluid waste generated in the OR.
PMID- 27509768
TI - Band Gap Engineering with Ultralarge Biaxial Strains in Suspended Monolayer MoS2.
AB - We demonstrate the continuous and reversible tuning of the optical band gap of
suspended monolayer MoS2 membranes by as much as 500 meV by applying very large
biaxial strains. By using chemical vapor deposition (CVD) to grow crystals that
are highly impermeable to gas, we are able to apply a pressure difference across
suspended membranes to induce biaxial strains. We observe the effect of strain on
the energy and intensity of the peaks in the photoluminescence (PL) spectrum and
find a linear tuning rate of the optical band gap of 99 meV/%. This method is
then used to study the PL spectra of bilayer and trilayer devices under strain
and to find the shift rates and Gruneisen parameters of two Raman modes in
monolayer MoS2. Finally, we use this result to show that we can apply biaxial
strains as large as 5.6% across micron-sized areas and report evidence for the
strain tuning of higher level optical transitions.
PMID- 27509769
TI - The population cost-effectiveness of delivering universal and indicated school
based interventions to prevent the onset of major depression among youth in
Australia.
AB - AIMS: School-based psychological interventions encompass: universal interventions
targeting youth in the general population; and indicated interventions targeting
youth with subthreshold depression. This study aimed to: (1) examine the
population cost-effectiveness of delivering universal and indicated prevention
interventions to youth in the population aged 11-17 years via primary and
secondary schools in Australia; and (2) compare the comparative cost
effectiveness of delivering these interventions using face-to-face and internet
based delivery mechanisms. METHODS: We reviewed literature on the prevention of
depression to identify all interventions targeting youth that would be suitable
for implementation in Australia and had evidence of efficacy to support analysis.
From this, we found evidence of effectiveness for the following intervention
types: universal prevention involving group-based psychological interventions
delivered to all participating school students; and indicated prevention
involving group-based psychological interventions delivered to students with
subthreshold depression. We constructed a Markov model to assess the cost
effectiveness of delivering universal and indicated interventions in the
population relative to a 'no intervention' comparator over a 10-year time
horizon. A disease model was used to simulate epidemiological transitions between
three health states (i.e., healthy, diseased and dead). Intervention effect sizes
were based on meta-analyses of randomised control trial data identified in the
aforementioned review; while health benefits were measured as Disability-adjusted
Life Years (DALYs) averted attributable to reductions in depression incidence.
Net costs of delivering interventions were calculated using relevant Australian
data. Uncertainty and sensitivity analyses were conducted to test model
assumptions. Incremental cost-effectiveness ratios (ICERs) were measured in 2013
Australian dollars per DALY averted; with costs and benefits discounted at 3%.
RESULTS: Universal and indicated psychological interventions delivered through
face-to-face modalities had ICERs below a threshold of $50 000 per DALY averted.
That is, $7350 per DALY averted (95% uncertainty interval (UI): dominates - 23
070) for universal prevention, and $19 550 per DALY averted (95% UI: 3081-56 713)
for indicated prevention. Baseline ICERs were generally robust to changes in
model assumptions. We conducted a sensitivity analysis which found that internet
delivered prevention interventions were highly cost-effective when assuming
intervention effect sizes of 100 and 50% relative to effect sizes observed for
face-to-face delivered interventions. These results should, however, be
interpreted with caution due to the paucity of data. CONCLUSIONS: School-based
psychological interventions appear to be cost-effective. However, realising
efficiency gains in the population is ultimately dependent on ensuring successful
system-level implementation.
PMID- 27509820
TI - A study on the glycemic, lipid and blood pressure control of type 2 diabetes
patients of Kerala.
AB - AIM: Aim of the study was to detect the level of comprehensive diabetes control
among the diabetic patients of Kerala, India. METHOD: Patients (1200) were
randomly selected from a diabetes care center. Their blood sugar and other
biochemical and anthropometric measurements were done and statistically analyzed.
RESULT: Only 28.3% had their A1C at or below 7% and 45% above 9%. 1/3rd of the
female and 1/5th of the male patients had CAD. The prevalence of hypertension was
almost equal in both sexes. However, there was a statistically significant higher
systolic BP (mean 162.12mm Hg vs 147.49mm Hg, p=0.01044) among females. The total
Cholesterol was above 200mg/dl in 42.1% of males and 45.61% of females. The
triglyceride was >150mg/dl in 38.6% males and 50.88% females. Low HDL cholesterol
levels were found in 20.07% of males and 41.12% of females (p=0.0445). The mean
LDL was 121.75 (+/-32.29247) DISCUSSION: The mean blood sugar values are found to
be high which will lead to a predictable increase in vascular disease, which in
turn will affect the quality of health and productivity of the individual and the
economic growth of the society as a whole. Studies suggest that therapeutic
interventions to improve glycemic control may reduce the risk of CVD and
microvascular disease. CONCLUSION: This study shows that the level of diabetes
control in Kerala is unsatisfactory. We need more medications, better strategies,
and more emphasis on glycemic management than we are currently able to apply.
PMID- 27509821
TI - Estimating the carrying capacity of green mussel cultivation by using net
nutrient removal model.
AB - This study aims to evaluate the nutrient removal potential and carrying capacity
of green mussel cultivation by using the mass balance model. The developed model
takes into consideration the green mussel growth rate, density and chlorophyll a
concentration. The data employed in this study were based on culture conditions
at Sriracha Fisheries Research Station, Thailand. Results show that net nutrient
removal by green mussel is 3302, 380, and 124mg/year/indv for carbon, nitrogen,
and phosphorus respectively. The carrying capacity of green mussel cultivation
was found to be 300indv/m2 based on chlorophyll a concentration which will not
release phosphorus in the water environment beyond the standard (45MUg-PO4-3
P/L). Higher chlorophyll a concentration results in lowered green mussel carrying
capacity. This model can assist farm operators with possible management
strategies for a sustainable mussel cultivation and protection of the marine
environment.
PMID- 27509822
TI - Macondo oil in deep-sea sediments: Part 2 - Distribution and distinction from
background and natural oil seeps.
AB - Following the Deepwater Horizon oil spill, the spilled Macondo oil was severely
weathered during its transport within the deep-sea plume as discrete particles,
which were subsequently deposited on the seafloor. The Macondo oil deposited in
deep-sea sediments was distinguished from ambient (background) hydrocarbons and
naturally-seeped and genetically-similar oils in the Mississippi Canyon region
using a forensic method based upon a systematic, multi-year study of 724 deep-sea
sediment cores collected in late 2010 and 2011. The method relied upon: (1)
chemical fingerprinting of the distinct features of the wax-rich, severely
weathered Macondo oil; (2) hydrocarbon concentrations, considering a core's
proximity to the Macondo well or to known or apparent natural oil seeps, and also
vertically within a core; and (3) results from proximal cores and flocculent
material from core supernatants and slurp gun filters. The results presented
herein establish the geographic extent of "fingerprintable" Macondo oil
recognized on the seafloor in 2010/2011.
PMID- 27509823
TI - Loophole-free Bell test using electron spins in diamond: second experiment and
additional analysis.
AB - The recently reported violation of a Bell inequality using entangled electronic
spins in diamonds (Hensen et al., Nature 526, 682-686) provided the first
loophole-free evidence against local-realist theories of nature. Here we report
on data from a second Bell experiment using the same experimental setup with
minor modifications. We find a violation of the CHSH-Bell inequality of 2.35 +/-
0.18, in agreement with the first run, yielding an overall value of S = 2.38 +/-
0.14. We calculate the resulting P-values of the second experiment and of the
combined Bell tests. We provide an additional analysis of the distribution of
settings choices recorded during the two tests, finding that the observed
distributions are consistent with uniform settings for both tests. Finally, we
analytically study the effect of particular models of random number generator
(RNG) imperfection on our hypothesis test. We find that the winning probability
per trial in the CHSH game can be bounded knowing only the mean of the RNG bias.
This implies that our experimental result is robust for any model underlying the
estimated average RNG bias, for random bits produced up to 690 ns too early by
the random number generator.
PMID- 27509824
TI - Multidrug-resistant surgical site infections in a humanitarian surgery project.
AB - The epidemiology of surgical site infections (SSIs) in surgical programmes in sub
Saharan Africa is inadequately described. We reviewed deep and organ-space SSIs
occurring within a trauma project that had a high-quality microbiology
partnership and active follow-up. Included patients underwent orthopaedic surgery
in Teme Hospital (Port Harcourt, Nigeria) for trauma and subsequently developed a
SSI requiring debridement and microbiological sampling. Data were collected from
structured chart reviews and programmatic databases for 103 patients with
suspected SSI [79% male, median age 30 years, interquartile range (IQR) 24-37].
SSIs were commonly detected post-discharge with 58% presenting >28 days after
surgery. The most common pathogens were: Staphylococcus aureus (34%), Pseudomonas
aeruginosa (16%) and Enterobacter cloacae (11%). Thirty-three (32%) of infections
were caused by a multidrug-resistant (MDR) pathogen, including 15 patients with
methicillin-resistant S. aureus. Antibiotics were initiated empirically for 43%
of patients and after culture and sensitivity report in 32%. The median number of
additional surgeries performed in patients with SSI was 5 (IQR 2-6), one patient
died (1%), and amputation was performed or recommended in three patients. Our
findings suggest the need for active long-term monitoring of SSIs, particularly
those associated with MDR organisms, resulting in increased costs for readmission
surgery and treatment with late-generation antibiotics.
PMID- 27509825
TI - The matricellular ligand Cyr61 contributes to the metastatic spread of tumors by
activating integrin VLA-4, independently of thiol redox modulation?.
PMID- 27509827
TI - Drug utilization and blood pressure control in ambulatory hypertensive patients:
focus on those with compelling indications.
AB - OBJECTIVE: Compelling indications require the use of specific antihypertensive
drug classes and often two or more antihypertensive medications for blood
pressure (BP) control. This study assessed drug utilization patterns among
hypertensive patients with compelling indications, conformity with recommended
guidelines, and the effect on BP control. MATERIALS AND METHODS: A prospective,
cross-sectional study of hypertensive patients attending three subspecialty
hospital clinics. Data on demographics, prescriptions, and BP were collected. BP
control was defined as BP less than 140/90 mmHg in nondiabetic subjects and less
than 130/80 for those with diabetes. Analysis was done with SPSS version 17.
RESULTS: Of the 1,926 patients with hypertension, 877 (45.5%) had compelling
indications. Patients were aged 59.3 +/- 11.5 years. The most frequently
encountered compelling indications were hypertensive heart disease (35.8%),
diabetic mellitus (31.9%), and renal diseases (11.5%). The most prescribed drug
was angiotensin-converting enzyme inhibitor (ACEIs), which was present in 22.6%
of all prescriptions. Only 23.1% of patients had fully controlled BP. Poor BP
control significantly correlated with the number of antihypertensive drugs r =
0.205, p < 0.001, but negatively correlated with age and duration of
hypertension, r = -0.071, p = 0.038 and r = -0.448, p = 0.042, respectively.
CONCLUSION: BP control was very poor in this study, and there was a high
prevalence of compelling indications. Poor control was negatively correlated with
increasing age and duration of hypertension. The most common compelling
indications were hypertensive heart disease, diabetes mellitus, and renal
disease.
PMID- 27509826
TI - Staphylococcus aureus osteo-articular infection: usefulness of the determination
of daptomycin serum concentration to explain a treatment failure.
AB - We report two cases of treatment failure in patients with osteoarticular
infection associated with Staphylococcus aureus bacteremia and receiving
daptomycin. Using a published population-pharmacokinetic model and daptomycin
blood level in these patients, area under the curve (AUC) was calculated and
compared to the pharmacological target. For the first patient, treated with 6
mg/kg every 48 hours due to acute renal failure and then every 24 hours, the AUC
was 820 mg*h*L-1, with a minimal concentration of 23.5 mg/L confirming
the right dose adjustment and the absence of underdosing. The methicillin
resistant Staphylococcus aureus (MRSA) strain was still susceptible to
daptomycin, but it was not sufficient to observe a favorable outcome. For the
second patient, treated with 10 mg/kg/d, the steady state residual concentration
was 10.4 mg/L, and the calculated AUC value was 550 mg*h*L-1. AUC/MIC
values evolved during treatment to be under the cut-off for bactericidal effects
(> 800 hours), and the Staphylococcus aureus (SA) strain became daptomycin
resistant. This study highlights the inter-individual pharmacokinetic variation
leading sometimes to drug underdosing. Drug monitoring should be encouraged in
order to avoid treatment failure.
PMID- 27509828
TI - Meperidine-induced QTc-interval prolongation: prevalence, risk factors, and
correlation to plasma drug and metabolite concentrations?.
AB - : A prolongation of the QTc-interval has been described for several opioids,
including pethidine (meperidine). OBJECTIVE: To evaluate in the clinical setting
the frequency and risk factors associated with the QT-interval prolongation
induced by meperidine. RESEARCH DESIGN AND METHODS: We recruited patients
requiring meperidine administration and recorded their medical history and
comorbidities predisposing to QT-interval prolongation. Ionograms and
electrocardiograms (ECGs) were performed at baseline and during treatment; QT was
corrected using the Bazzet, Fridericia, Framinghan, and Hogdes formulas. We
measured meperidine and normeperidine by gas chromatography. Values are expressed
as mean +/- SD (range). RESULTS: 58 patients were studied (43.1% males). All
patients received meperidine at a dose of 304 +/- 133 (120 - 480) mg/day.
Meperidine and normeperidine concentrations were 369 +/- 60 (265 - 519) and 49 +/
17 (15 - 78) ng/mL, respectively. Intratreatment control found QTcB 370 +/- 30
(305 - 433), QTcFri 353 +/- 35 (281 - 429), QTcFra 360 +/- 30 (299 - 429), QTcH
359 +/- 27 (304 - 427), DeltaQTcB +9 +/- 42 (-90 to +136), DeltaQTcFri +4 +/- 45
(-86 to +137), DeltaQTcFra +5 +/- 40 (-77 to +129), and DeltaQTcH +7 +/- 40 (-76
to +129) ms. Meperidine concentration correlated with QTc-interval (R > 0.36) and
DeltaQTc (R > 0.69) but the correlation was even better for normeperidine
concentration, QTc (R > 0.52) and DeltaQTc (R > 0.81). Depending on the QTc
correction formula used, 13 - 15 patients (22.41 - 25.86%) presented DeltaQTc
values > 30 ms, and 7 - 8 patients (12.07- 13.79%) showed DeltaQTc values > 60
ms. Renal failure was associated with risk for DeltaQTc > 30 ms of 3.74 (IC95%
1.73 - 8.10) and for DeltaQTc > 60 ms of 4.27 (IC 95% 1.26 - 14.48). No patient
developed arrhythmias during the study. CONCLUSIONS: Meperidine treatment causes
ECG changes (QTc-interval prolongation) in high correlation with normeperidine
plasma concentration. Renal failure increases the risk.?.
PMID- 27509829
TI - Direct influence of systemic desensitization by resiniferatoxin on the activities
of Adelta- and C-fibers in the rat primary bladder mechanosensitive afferent
nerves.
AB - OBJECTIVES: To examine whether systemic resiniferatoxin treatment can desensitize
the single-unit afferent activities of Adelta- and C-fibers in rat primary
bladder mechanosensitive afferent nerves. METHODS: Female Sprague-Dawley rats
were divided into two groups (resiniferatoxin-treated: n = 9, vehicle-treated: n
= 9). Resiniferatoxin (0.3 mg/kg) or its vehicle (10% ethanol) was injected
subcutaneously after the first eye-wipe behavior test with capsaicin. The second
eye-wipe behavior test was carried out 48 h after the injection under urethane
(1.2 g/kg intraperitoneally) anesthesia. The bladder mechanosensitive single-unit
afferent activities originating from the left L6 dorsal roots were identified by
electrical stimulation of the left pelvic nerve and bladder distension, and
classified by conduction velocity as either Adelta-fibers or C-fibers. The single
unit afferent activity measurements were carried out with constant bladder
filling with saline (0.1 mL/min, <30 cmH2 O). RESULTS: After resiniferatoxin
treatment, but not vehicle treatment, eye-wipe behavior with capsaicin was
completely abolished. A total of 104 single afferent fibers were isolated (Adelta
fibers: n = 41, C-fibers: n = 63). Single-unit afferent activities of both Adelta
fibers and C-fibers in response to bladder filling in the resiniferatoxin-treated
group were significantly lower than those in the vehicle-treated group. These
differences were observed throughout the filling phase in Adelta-fibers and
during the initial half of the filling phase in C-fibers. CONCLUSIONS: The
present results show the existence of resiniferatoxin desensitization-resistant
mechanosensitive Adelta- and C-fibers in rat primary bladder afferent nerves,
suggesting that systemic resiniferatoxin treatment might induce non-specific
partial desensitization or denervation of mechanosensitive capsaicin-insensitive
Adelta- and C-fibers of the rat bladder.
PMID- 27509830
TI - Technological aids for improving longitudinal research on substance use
disorders.
AB - BACKGROUND: There is a broad consensus that addictive behaviors tend to be
chronic and relapsing. But for field studies of substance users, successfully
tracking, locating, and following up with a representative sample of subjects is
a challenge. METHODS: The purpose of this paper is to provide a general overview
of how current technological aids can support and improve the quality of
longitudinal research on substance use disorders. The review is grouped into four
domains: (1) tracking and locating, (2) prompting/engaging, (3) incentivizing,
and (4) collecting data. RESULTS & CONCLUSIONS: Although the technologies
described in this review will be modified or replaced over time, our findings
suggest that incorporating some or all of these currently available approaches
may improve research efficiency, follow-up rates, and data quality.
PMID- 27509832
TI - Hydrated forms of fluoroacetic acid: a rotational study.
AB - The rotational spectra of two conformers of the 1 : 1 adduct of fluoroacetic acid
with water have been assigned by pulsed jet Fourier transform microwave
spectroscopy. Their shapes differ according to the trans and cis forms of the
fluoroacetic acid moiety. This is in contrast to the rotational spectrum of the
monomer, for which the cis form has not been observed. Details of the hydrogen
bond, structure, dynamics and energetic features of the two species are given.
PMID- 27509831
TI - Predicting bee community responses to land-use changes: Effects of geographic and
taxonomic biases.
AB - Land-use change and intensification threaten bee populations worldwide,
imperilling pollination services. Global models are needed to better
characterise, project, and mitigate bees' responses to these human impacts. The
available data are, however, geographically and taxonomically unrepresentative;
most data are from North America and Western Europe, overrepresenting bumblebees
and raising concerns that model results may not be generalizable to other regions
and taxa. To assess whether the geographic and taxonomic biases of data could
undermine effectiveness of models for conservation policy, we have collated from
the published literature a global dataset of bee diversity at sites facing land
use change and intensification, and assess whether bee responses to these
pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe;
North, Central and South America; Australia and New Zealand; South East Asia;
Middle and Southern Africa) and between bumblebees and other bees. Our analyses
highlight strong regionally-based responses of total abundance, species richness
and Simpson's diversity to land use, caused by variation in the sensitivity of
species and potentially in the nature of threats. These results suggest that
global extrapolation of models based on geographically and taxonomically
restricted data may underestimate the true uncertainty, increasing the risk of
ecological surprises.
PMID- 27509833
TI - Small bowel intussusception from renal cell carcinoma metastasis: a case report
and review of the literature.
AB - BACKGROUND: Renal cell carcinoma is the most frequent malignant neoplasia of the
kidney accounting for 90 % of all renal solid tumors. Metastases from renal cell
carcinoma are rarely located in the small bowel and generally their clinical
presentation includes bleeding and obstruction. Intussusception in adults is an
extremely rare pathological condition and only 30 to 35 % of small bowel
intussusceptions are derived from malignant lesions. CASE PRESENTATION: We report
here a clinical case of a 75-year-old white man hospitalized for anemia and
subocclusion. An abdominal ultrasound and computed tomography showed a small
bowel intussusception. During a surgical exploration, a polypoid lesion was found
to be the lead point of the intussusception. His small intestine was resected and
a functional side-to-side anastomosis was performed. The histological features of
the surgical specimen confirmed the diagnosis of metastatic renal cell carcinoma.
CONCLUSIONS: Small bowel intussusception from renal cell carcinoma metastasis
should always be considered in the setting of unexplained intestinal subocclusion
in patients with a history of renal cell carcinoma.
PMID- 27509834
TI - Bone-density testing interval and transition to osteoporosis in patients with
rheumatoid arthritis.
AB - : The study aims to evaluate the rate of transition to osteoporosis in 360 RA
patients and estimate the rescreening intervals of bone mineral density (BMD)
testing. Osteoporosis was newly developed in 24.8 % during mean follow-up of 7.4
years. The estimated time of a BMD testing interval was dependent on the baseline
T-score in RA patients. INTRODUCTION: Although BMD testing is routinely performed
in RA patients, the interval between BMD tests has not been determined. METHODS:
We retrospectively recruited 360 consecutive female patients with RA, who
underwent repeated BMD testing, with a mean age of 53.7 +/- 10.2 years and a mean
follow-up duration of 7.4 +/- 5.0 years. We stratified the study participants
into five groups based on their baseline T-score range. The testing interval was
defined as the estimated time for 10 % of patients in each subgroup to transition
to osteoporosis. Competing-risk analyses were performed with sensitivity analysis
by menopausal status and risk factors for transition to osteoporosis. RESULTS: At
baseline, 15 % of screened patients had osteoporosis, and during follow-up, that
proportion increased to 24.8 %. The estimated BMD testing interval for 10 % of
patients to develop osteoporosis was 9.6 years for those with normal BMD, 7.6
years for those with mild osteopenia, 4.7 years for those with moderate
osteopenia, and 2.1 years for those with severe osteopenia. No significant risk
factor for transition to osteoporosis was identified in this cohort. CONCLUSIONS:
Our data indicate that osteoporosis will develop in less than 10 % of female RA
patients during rescreening intervals of approximately 9 years for those with
normal bone density at baseline, 7 years for those with mild osteopenia, 4 years
for those with moderate osteopenia, and 2 years for those with severe osteopenia
at baseline. BMD interval in RA patients could be adjusted according to their
baseline BMD T-scores.
PMID- 27509835
TI - DNA sequence analysis in 598 individuals with a clinical diagnosis of
osteogenesis imperfecta: diagnostic yield and mutation spectrum.
AB - : We detected disease-causing mutations in 585 of 598 individuals (98 %) with
typical features of osteogenesis imperfecta (OI). In mild OI, only collagen type
I encoding genes were involved. In moderate to severe OI, mutations in 12
different genes were found; 11 % of these patients had mutations in recessive
genes. INTRODUCTION: OI is usually caused by mutations in COL1A1 or COL1A2, the
genes encoding collagen type I alpha chains, but mutations in at least 16 other
genes have also been associated with OI. It is presently unknown what proportion
of individuals with clinical features of OI has a disease-causing mutation in one
of these genes. METHODS: DNA sequence analysis was performed on 598 individuals
from 487 families who had a typical OI phenotype. OI type I was diagnosed in 43 %
of individuals, and 57 % had moderate to severe OI, defined as OI types other
than type I. RESULTS: Disease-causing variants were detected in 97 % of
individuals with OI type I and in 99 % of patients with moderate to severe OI.
All mutations found in OI type I were dominant and exclusively affected COL1A1 or
COL1A2. In moderate to severe OI, dominant mutations were found in COL1A1/COL1A2
(77 %), IFITM5 (9 %), and P4HB (0.6 %). Mutations in one of the recessive OI
associated gene were observed in 12 % of individuals with moderate to severe OI.
The genes most frequently involved in recessive OI were SERPINF1 (4.0 % of
individuals with moderate to severe OI) and CRTAP (2.9 %). CONCLUSIONS: DNA
sequence analysis of currently known OI-associated genes identifies disease
causing variants in almost all individuals with a typical OI phenotype. About 20
% of individuals with moderate to severe OI had mutations in genes other than
COL1A1/COL1A2.
PMID- 27509836
TI - MRI-based quantitative susceptibility mapping (QSM) and R2* mapping of liver iron
overload: Comparison with SQUID-based biomagnetic liver susceptometry.
AB - PURPOSE: We aimed to determine the agreement between quantitative susceptibility
mapping (QSM)-based biomagnetic liver susceptometry (BLS) and confounder
corrected R2* mapping with superconducting quantum interference device (SQUID)
based biomagnetic liver susceptometry in patients with liver iron overload.
METHODS: Data were acquired from two healthy controls and 22 patients undergoing
MRI and SQUID-BLS as part of routine monitoring for iron overload. Magnetic
resonance imaging was performed on a 3T system using a three-dimensional multi
echo gradient-echo acquisition. Both magnetic susceptibility and R2* of the liver
were estimated from this acquisition. Linear regression was used to compare
estimates of QSM-BLS and R2* to SQUID-BLS. RESULTS: Both QSM-BLS and confounder
corrected R2* were sensitive to the presence of iron in the liver. Linear
regression between QSM-BLS and SQUID-BLS demonstrated the following relationship:
QSM-BLS = (-0.22 +/- 0.11) + (0.49 +/- 0.05) . SQUID-BLS with r2 = 0.88. The
coefficient of determination between liver R2* and SQUID-BLS was also r2 = 0.88.
CONCLUSION: We determined a strong correlation between both QSM-BLS and
confounder-corrected R2* to SQUID-BLS. This study demonstrates the feasibility of
QSM-BLS and confounder-corrected R2* for assessing liver iron overload,
particularly when SQUID systems are not accessible. Magn Reson Med 78:264-270,
2017. (c) 2016 International Society for Magnetic Resonance in Medicine.
PMID- 27509837
TI - Molecularly Rigid Microporous Polyamine Captures and Stabilizes Conducting
Platinum Nanoparticle Networks.
AB - A molecularly rigid polyamine based on a polymer of intrinsic microporosity (PIM
EA-TB) is shown to capture and stabilize platinum nanoparticles during colloid
synthesis in the rigid framework. Stabilization here refers to avoiding
aggregation without loss of surface reactivity. In the resulting rigid framework
with embedded platinum nanoparticles, the volume ratio of platinum to PIM-EA-TB
in starting materials is varied systematically from approximately 1.0 to 0.1 with
the resulting platinum nanoparticle diameter varying from approximately 4.2 to
3.1 nm, respectively. Elemental analysis suggests that only a fraction of the
polymer is "captured" to give nanocomposites rich in platinum. A transition
occurs from electrically conducting and electrochemically active (with shorter
average interparticle distance) to nonconducting and only partially
electrochemically active (with longer average interparticle distance) polymer
platinum composites. The conducting nanoparticle network in the porous rigid
macromolecular framework could be beneficial in electrocatalysis and in sensing
applications.
PMID- 27509838
TI - Microbial Biotechnology-2020.
PMID- 27509839
TI - Attachment Dimensions and Post-traumatic Symptoms Following Interpersonal Traumas
versus Impersonal Traumas in Young Adults in Taiwan.
AB - Greater risk of post-traumatic stress disorder (PTSD) is seen in individuals
exposed to interpersonal traumatic events. Based on an attachment perspective,
interpersonal trauma exposure may activate one's attachment insecurity system and
disrupt affect, behaviour and interpersonal function, which may in turn create
more difficulties to cope with interpersonal traumas and exacerbate PTSD
symptomatology. The present study examined whether attachment anxiety relative to
attachment avoidance would be a stronger predictor of greater PTSD symptoms
following interpersonal traumas versus impersonal traumas in a Taiwanese sample.
One hundred and sixty-two trauma-exposed Taiwanese young adults completed the
measures of symptoms of depression, anxiety and PTSD, and attachment anxiety and
attachment avoidance. In this Taiwanese study, higher attachment anxiety was
observed in individuals who were exposed to interpersonal traumas. The
interpersonal trauma group reported greater PTSD symptoms than did the impersonal
trauma group. Specifically, after controlling for age, occurrence of trauma and
distress of trauma, attachment anxiety, but not attachment avoidance, predicted
more PTSD total severity and avoidance symptoms in the interpersonal trauma
group. The findings may be pertinent to attachment anxiety-related
hyperactivating strategies, as well as specific cultural values and a forbearance
strategy applied to regulate traumatic distress in a collectivist society.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27509840
TI - Effect of Regional Intravenous Limb Perfusate Volume on Synovial Fluid
Concentration of Amikacin and Local Venous Blood Pressure in the Horse.
AB - OBJECTIVE: To determine the effect of volume of amikacin perfusate for
intravenous regional limb perfusion (IVRLP) via the cephalic vein in standing,
sedated horses on (1) amikacin concentrations in the synovial fluid of the
radiocarpal joint (RCJ) and distal interphalangeal joint (DIPJ) and, (2) amikacin
concentration in the systemic circulation, and (3) regional intravenous pressure.
STUDY DESIGN: Randomized cross-over design. ANIMALS: Six adult horses. METHODS:
Each horse received IVRLP using 4 perfusate volumes (10, 30, 60 & 120 ml) in
random order, after a minimum of 1 week washout. After application of a pneumatic
tourniquet, IVRLP with 1 g of amikacin in 0.9% NaCl was performed. Synovial fluid
from the RCJ and DIPJ, and systemic and regional venous blood were sampled, and
regional blood pressure was measured, immediately before perfusion (time 0), and
15 and 30 minutes after perfusion but before tourniquet release. RESULTS: No
difference was observed in the mean amikacin concentration of synovial fluid for
the 4 perfusate volumes (P>.09). For all volumes, mean amikacin concentration for
DIPJ synovial fluid was higher than for RCJ (P<.0001). The mean amikacin
concentration in DIPJ synovial fluid was therapeutic for resistant pathogens
using the 10, 60, and 120 mL volumes but the mean amikacin concentration for RCJ
synovial fluid was not therapeutic for resistant pathogens with any perfusate
volume. All volumes resulted in an immediate increase in mean regional
intravascular pressure after perfusion (P<.0001) but was not different across the
4 perfusate volumes. CONCLUSION: Cephalic IVRLP of 1 g of amikacin diluted to a
volume of 10-120 mL with 0.9% NaCl will achieve amikacin concentrations
therapeutic for resistant pathogens in the synovial fluid from the DIPJ.
Concentrations below therapeutic levels for resistant pathogens are reached in
the synovial fluid from the RCJ.
PMID- 27509842
TI - Vitamin D status in Poland.
AB - INTRODUCTION Epidemiological data on vitamin D status in the Polish population
are limited. OBJECTIVES The aim of the study was to evaluate the vitamin D
status in a representative group of adult inhabitants of 22 Polish cities, based
on the analysis of serum 25-hydroxyvitamin D [25(OH)D] levels. PATIENTS AND
METHODS This cross-sectional study included a total of 5775 adult volunteers
(4464 women; 1311 men; mean age, 54.0 +/-15.9 years; range, 15.6-89.8 years), who
were enrolled and examined through late winter and spring 2014. Serum
concentrations of 25(OH)D were determined using the Liaison XL system (DiaSorin;
CLIA method). Demographic and anthropometric data were also analyzed. RESULTS
The mean 25(OH)D concentration in the studied population was 18.0 +/-9.6 ng/ml;
65.8% of the patients had 25(OH)D levels of less than 20 ng/ml; 24.1% had
suboptimal levels of 20 to 30 ng/ml; and only 9.1% demonstrated the optimal
levels of 30 to 50 ng/ml. In 89.9% of the studied population, 25(OH)D levels of
less than 30 ng/ml were found. Obesity, defined as body mass index (BMI) over 30
kg/m2, was associated with lower 25(OH)D levels compared with normal weight (15.8
+/-8.5 vs 18.5 +/-9.7 ng/ml; P <0.0001). Lower 25(OH)D levels were observed in
men, younger individuals, and individuals with excess body weight and higher BMI.
CONCLUSIONS The results of our study, which involved the most representative
sample size of Polish adults, support the previously reported data on vitamin D
status. The levels of 25(OH)D determined for adults in our study demonstrate that
the majority of the Polish population is vitamin D deficient, at least during
winter and spring, and that preventive or interventional strategies must be
considered to improve the vitamin D status in Poland.
PMID- 27509841
TI - Early activation of MyD88-mediated autophagy sustains HSV-1 replication in human
monocytic THP-1 cells.
AB - Autophagy is a cellular degradation pathway that exerts numerous functions in
vital biological processes. Among these, it contributes to both innate and
adaptive immunity. On the other hand, pathogens have evolved strategies to
manipulate autophagy for their own advantage. By monitoring autophagic markers,
we showed that HSV-1 transiently induced autophagosome formation during early
times of the infection of monocytic THP-1 cells and human monocytes. Autophagy is
induced in THP-1 cells by a mechanism independent of viral gene expression or
viral DNA accumulation. We found that the MyD88 signaling pathway is required for
HSV-1-mediated autophagy, and it is linked to the toll-like receptor 2 (TLR2).
Interestingly, autophagy inhibition by pharmacological modulators or siRNA
knockdown impaired viral replication in both THP-1 cells and human monocytes,
suggest that the virus exploits the autophagic machinery to its own benefit in
these cells. Taken together, these findings indicate that the early autophagic
response induced by HSV-1 exerts a proviral role, improving viral production in a
semi-permissive model such as THP-1 cells and human monocytes.
PMID- 27509843
TI - Stratification of responders towards eculizumab using a structural epitope
mapping strategy.
AB - The complement component 5 (C5)-binding antibody eculizumab is used to treat
patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic
uremic syndrome (aHUS). As recently reported there is a need for a precise
classification of eculizumab responsive patients to allow for a safe and cost
effective treatment. To allow for such stratification, knowledge of the precise
binding site of the drug on its target is crucial. Using a structural epitope
mapping strategy based on bacterial surface display, flow cytometric sorting and
validation via haemolytic activity testing, we identified six residues essential
for binding of eculizumab to C5. This epitope co-localizes with the contact area
recently identified by crystallography and includes positions in C5 mutated in
non-responders. The identified epitope also includes residue W917, which is
unique for human C5 and explains the observed lack of cross-reactivity for
eculizumab with other primates. We could demonstrate that Ornithodorus moubata
complement inhibitor (OmCI), in contrast to eculizumab, maintained anti
haemolytic function for mutations in any of the six epitope residues, thus
representing a possible alternative treatment for patients non-responsive to
eculizumab. The method for stratification of patients described here allows for
precision medicine and should be applicable to several other diseases and
therapeutics.
PMID- 27509844
TI - A matched comparison study of hepatitis C treatment outcomes in the prison and
community setting, and an analysis of the impact of prison release or transfer
during therapy.
AB - Prisoners are a priority group for hepatitis C (HCV) treatment. Although
treatment durations will become shorter using directly acting antivirals (DAAs),
nearly half of prison sentences in Scotland are too short to allow completion of
DAA therapy prior to release. The purpose of this study was to compare treatment
outcomes between prison- and community-based patients and to examine the impact
of prison release or transfer during therapy. A national database was used to
compare treatment outcomes between prison treatment initiates and a matched
community sample. Additional data were collected to investigate the impact of
release or transfer on treatment outcomes. Treatment-naive patients infected with
genotype 1/2/3/4 and treated between 2009 and 2012 were eligible for inclusion.
291 prison initiates were matched with 1137 community initiates: SVRs were 61%
(95% CI 55%-66%) and 63% (95% CI 60%-66%), respectively. Odds of achieving a SVR
were not significantly associated with prisoner status (P=.33). SVRs were 74%
(95% CI 65%-81%), 59% (95% CI 42%-75%) and 45% (95% CI 29%-62%) among those not
released or transferred, transferred during treatment, or released during
treatment, respectively. Odds of achieving a SVR were significantly associated
with release (P<.01), but not transfer (P=.18). Prison-based HCV treatment
achieves similar outcomes to community-based treatment, with those not released
or transferred during treatment doing particularly well. Transfer or release
during therapy should be avoided whenever possible, using anticipatory planning
and medical holds where appropriate.
PMID- 27509845
TI - A pilot study of parent education intervention improves early childhood
development among toddlers with sickle cell disease.
AB - BACKGROUND: Young children with sickle cell disease (SCD) are at risk for
cognitive delay. In addition to biologic risk factors associated with SCD,
environmental factors contribute to cognitive dysfunction within this cohort.
METHODS: We completed a single-arm, prospective cohort study. Children with SCD
between the ages of 3 and 36 months and their caregivers were followed between
October 2010 and December 2013. The aim was to describe the role of a home
visitation model, the home environment, and socioeconomic status in the
development of young children with SCD. Primary outcome measures were the Bayley
Scales of Infant and Toddler Development, Third Edition (BSID-III) and the Home
Observation for Measurement of the Environment (HOME). We hypothesized that the
home visitation model, Parents as Teachers(r) (PAT), would encourage positive
parent-child interactions and improve cognitive outcomes. RESULTS: Thirty-five
participants had at least two PAT visits and BSID-III assessments. Mean scores
within all five subtests of the BSID-III improved between enrollment and exit,
with significant changes within cognitive (P = 0.016) and expressive language
(EL) domains (P = 0.002). Multivariate modeling found the HOME score associated
with the exit results of the cognitive domain. CONCLUSION: We report longitudinal
results of the first home visitation program within the early childhood SCD
population and show significant improvement in cognitive and EL development.
Additionally, home environment was a significant predictor of cognitive
development. Randomized controlled trials to test the impact of interventions
targeting the home environment are warranted for this vulnerable population.
PMID- 27509846
TI - EBP50 interacts with EGFR and regulates EGFR signaling to affect the prognosis of
cervical cancer patients.
AB - Ezrin-radixin-moesin-binding phosphoprotein-50 (EBP50) has a role in the
occurrence and progression of multiple types of tumors. However, its role in
cervical cancer (CC) remain unknown. EBP50 was reported to interact with
epidermal growth factor receptor (EGFR) and regulate EGFR signaling in CC HeLa
cells. In this study, the effect of EBP50 expression on CC cell proliferation and
prognosis of CC patients by regulating EGFR signaling was investigated. We found
that EBP50 expression level was significantly downregulated in CC tissues. EBP50
expression negatively correlated with CC cell proliferation, cell cycle and the
activation of EGFR-mediated ERK signaling. EBP50 knockdown abolished its
inhibition on EGF-induced ERK activation, suggesting EBP50 regulated EGFR
signaling. In order to further explore EBP50 regulated EGFR signaling via
interaction, we constructed EBP50_DD mutant which disrupted its interaction with
EGFR. EBP50_DD overexpression attenuated the inhibition of EBP50_WT on EGFR
mediated ERK signaling, further revealing EBP50 regulated EGFR signaling via its
interaction with EGFR. EGFR activation was associated with poor prognosis of CC
patients. EBP50 could not predict the prognosis of all CC patients. However,
after ruling out patients with egfr/ErbB mutation or copy number variation (CNV)
and (chemo)radiation, which caused continuous EGFR activation and affected the
prognosis of patients, respectively, EBP50 expression level exhibited the
prognosis prediction ability, revealing EBP50 affected prognosis of CC patients
via regulating EGFR signaling. In conclusion, EBP50 played an important role in
CC cell proliferation and prognosis prediction of CC patients by interacting with
EGFR and regulating EGFR signaling. EBP50 might be a potential precise
therapeutic target or prognostic marker for CC patients.
PMID- 27509848
TI - Facial feedback and autonomic responsiveness reflect impaired emotional
processing in Parkinson's Disease.
AB - Emotional deficits are part of the non-motor features of Parkinson's disease but
few attention has been paid to specific aspects such as subjective emotional
experience and autonomic responses. This study aimed to investigate the
mechanisms of emotional recognition in Parkinson's Disease (PD) using the
following levels: explicit evaluation of emotions (Self-Assessment Manikin) and
implicit reactivity (Skin Conductance Response; electromyographic measure of
facial feedback of the zygomaticus and corrugator muscles). 20 PD Patients and 34
healthy controls were required to observe and evaluate affective pictures during
physiological parameters recording. In PD, the appraisal process on both valence
and arousal features of emotional cues were preserved, but we found significant
impairment in autonomic responses. Specifically, in comparison to healthy
controls, PD patients revealed lower Skin Conductance Response values to negative
and high arousing emotional stimuli. In addition, the electromyographic measures
showed defective responses exclusively limited to negative and high arousing
emotional category: PD did not show increasing of corrugator activity in response
to negative emotions as happened in heathy controls. PD subjects inadequately
respond to the emotional categories which were considered more "salient": they
had preserved appraisal process, but impaired automatic ability to distinguish
between different emotional contexts.
PMID- 27509849
TI - FGFR3 preferentially colocalizes with IGH in the interphase nucleus of multiple
myeloma patient B-cells when FGFR3 is located outside of CT4.
AB - Many B-cell malignancies are characterized by chromosomal translocations
involving IGH and a proto-oncogene. For translocations to occur, spatial
proximity of translocation-prone genes is necessary. Currently, it is not known
how such genes are brought into proximity with one another. Although decondensed
chromosomes occupy definitive, non-random spaces in the interphase nucleus known
as chromosome territories (CTs), chromatin at the edges of CTs can intermingle,
and specific genomic regions from some chromosomes have been shown to "loop out"
of their respective CTs. This extra-territorial positioning of specific genomic
regions may provide a mechanism whereby translocation-prone genes are brought
together in the interphase nucleus. FGFR3 and MAF recurrently participate in
translocations with IGH at different frequencies. Using 3D, 4-color FISH, and 3D
analysis software, we show frequent extra-territorial positioning of FGFR3 and
significantly less frequent extra-territorial positioning of MAF. Frequent extra
territorial positioning may be characteristic of FGFR3 in B-cells from healthy
adult donors and non-malignant B-cells from patients, but not in hematopoietic
stem cells from patients with translocations. The frequency of extra-territorial
positioning of FGFR3 and MAF in B-cells correlates with the frequency of
translocations in the patient population. Most importantly, in patient B-cells,
we demonstrate a significant proportion of extra-territorial FGFR3 participating
in close loci pairs and/or colocalizing with IGH. This preliminary work suggests
that in patient B-cells, extra-territorial positioning of FGFR3 may provide a
mechanism for forming close loci pairs and/or colocalization with IGH; indirectly
facilitating translocation events involving these two genes. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27509850
TI - A human neurodevelopmental model for Williams syndrome.
AB - Williams syndrome is a genetic neurodevelopmental disorder characterized by an
uncommon hypersociability and a mosaic of retained and compromised linguistic and
cognitive abilities. Nearly all clinically diagnosed individuals with Williams
syndrome lack precisely the same set of genes, with breakpoints in chromosome
band 7q11.23 (refs 1-5). The contribution of specific genes to the
neuroanatomical and functional alterations, leading to behavioural pathologies in
humans, remains largely unexplored. Here we investigate neural progenitor cells
and cortical neurons derived from Williams syndrome and typically developing
induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have
an increased doubling time and apoptosis compared with typically developing
neural progenitor cells. Using an individual with atypical Williams syndrome, we
narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9).
At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome
were characterized by longer total dendrites, increased numbers of spines and
synapses, aberrant calcium oscillation and altered network connectivity.
Morphometric alterations observed in neurons from Williams syndrome were
validated after Golgi staining of post-mortem layer V/VI cortical neurons. This
model of human induced pluripotent stem cells fills the current knowledge gap in
the cellular biology of Williams syndrome and could lead to further insights into
the molecular mechanism underlying the disorder and the human social brain.
PMID- 27509851
TI - A progressively wetter climate in southern East Africa over the past 1.3 million
years.
AB - African climate is generally considered to have evolved towards progressively
drier conditions over the past few million years, with increased variability as
glacial-interglacial change intensified worldwide. Palaeoclimate records derived
mainly from northern Africa exhibit a 100,000-year (eccentricity) cycle
overprinted on a pronounced 20,000-year (precession) beat, driven by orbital
forcing of summer insolation, global ice volume and long-lived atmospheric
greenhouse gases. Here we present a 1.3-million-year-long climate history from
the Lake Malawi basin (10 degrees -14 degrees S in eastern Africa), which
displays strong 100,000-year (eccentricity) cycles of temperature and rainfall
following the Mid-Pleistocene Transition around 900,000 years ago. Interglacial
periods were relatively warm and moist, while ice ages were cool and dry. The
Malawi record shows limited evidence for precessional variability, which we
attribute to the opposing effects of austral summer insolation and the
temporal/spatial pattern of sea surface temperature in the Indian Ocean. The
temperature history of the Malawi basin, at least for the past 500,000 years,
strongly resembles past changes in atmospheric carbon dioxide and terrigenous
dust flux in the tropical Pacific Ocean, but not in global ice volume. Climate in
this sector of eastern Africa (unlike northern Africa) evolved from a
predominantly arid environment with high-frequency variability to generally
wetter conditions with more prolonged wet and dry intervals.
PMID- 27509852
TI - Postglacial viability and colonization in North America's ice-free corridor.
AB - During the Last Glacial Maximum, continental ice sheets isolated Beringia
(northeast Siberia and northwest North America) from unglaciated North America.
By around 15 to 14 thousand calibrated radiocarbon years before present (cal. kyr
bp), glacial retreat opened an approximately 1,500-km-long corridor between the
ice sheets. It remains unclear when plants and animals colonized this corridor
and it became biologically viable for human migration. We obtained radiocarbon
dates, pollen, macrofossils and metagenomic DNA from lake sediment cores in a
bottleneck portion of the corridor. We find evidence of steppe vegetation, bison
and mammoth by approximately 12.6 cal. kyr bp, followed by open forest, with
evidence of moose and elk at about 11.5 cal. kyr bp, and boreal forest
approximately 10 cal. kyr bp. Our findings reveal that the first Americans,
whether Clovis or earlier groups in unglaciated North America before 12.6 cal.
kyr bp, are unlikely to have travelled by this route into the Americas. However,
later groups may have used this north-south passageway.
PMID- 27509853
TI - Structural biology: Catalytic spliceosome captured.
PMID- 27509854
TI - Structure of mammalian respiratory complex I.
AB - Complex I (NADH:ubiquinone oxidoreductase), one of the largest membrane-bound
enzymes in the cell, powers ATP synthesis in mammalian mitochondria by using the
reducing potential of NADH to drive protons across the inner mitochondrial
membrane. Mammalian complex I (ref. 1) contains 45 subunits, comprising 14 core
subunits that house the catalytic machinery (and are conserved from bacteria to
humans) and a mammalian-specific cohort of 31 supernumerary subunits. Knowledge
of the structures and functions of the supernumerary subunits is fragmentary.
Here we describe a 4.2-A resolution single-particle electron cryomicroscopy
structure of complex I from Bos taurus. We have located and modelled all 45
subunits, including the 31 supernumerary subunits, to provide the entire
structure of the mammalian complex. Computational sorting of the particles
identified different structural classes, related by subtle domain movements,
which reveal conformationally dynamic regions and match biochemical descriptions
of the 'active-to-de-active' enzyme transition that occurs during hypoxia. Our
structures therefore provide a foundation for understanding complex I assembly
and the effects of mutations that cause clinically relevant complex I
dysfunctions, give insights into the structural and functional roles of the
supernumerary subunits and reveal new information on the mechanism and regulation
of catalysis.
PMID- 27509855
TI - Cell division: Mitotic regulation comes into focus.
PMID- 27509856
TI - Natural courtship song variation caused by an intronic retroelement in an ion
channel gene.
AB - Animal species display enormous variation for innate behaviours, but little is
known about how this diversity arose. Here, using an unbiased genetic approach,
we map a courtship song difference between wild isolates of Drosophila simulans
and Drosophila mauritiana to a 966 base pair region within the slowpoke (slo)
locus, which encodes a calcium-activated potassium channel. Using the reciprocal
hemizygosity test, we confirm that slo is the causal locus and resolve the causal
mutation to the evolutionarily recent insertion of a retroelement in a slo intron
within D. simulans. Targeted deletion of this retroelement reverts the song
phenotype and alters slo splicing. Like many ion channel genes, slo is expressed
widely in the nervous system and influences a variety of behaviours; slo-null
males sing little song with severely disrupted features. By contrast, the natural
variant of slo alters a specific component of courtship song, illustrating that
regulatory evolution of a highly pleiotropic ion channel gene can cause modular
changes in behaviour.
PMID- 27509857
TI - HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA
synthesis.
AB - During the early stages of infection, the HIV-1 capsid protects viral components
from cytosolic sensors and nucleases such as cGAS and TREX, respectively, while
allowing access to nucleotides for efficient reverse transcription. Here we show
that each capsid hexamer has a size-selective pore bound by a ring of six
arginine residues and a 'molecular iris' formed by the amino-terminal beta
hairpin. The arginine ring creates a strongly positively charged channel that
recruits the four nucleotides with on-rates that approach diffusion limits.
Progressive removal of pore arginines results in a dose-dependent and concomitant
decrease in nucleotide affinity, reverse transcription and infectivity. This
positively charged channel is universally conserved in lentiviral capsids despite
the fact that it is strongly destabilizing without nucleotides to counteract
charge repulsion. We also describe a channel inhibitor, hexacarboxybenzene, which
competes for nucleotide binding and efficiently blocks encapsidated reverse
transcription, demonstrating the tractability of the pore as a novel drug target.
PMID- 27509858
TI - Pancreatic stellate cells support tumour metabolism through autophagic alanine
secretion.
AB - Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by
an intense fibrotic stromal response and deregulated metabolism. The role of the
stroma in PDAC biology is complex and it has been shown to play critical roles
that differ depending on the biological context. The stromal reaction also
impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment.
As such, these tumours must alter how they capture and use nutrients to support
their metabolic needs. Here we show that stroma-associated pancreatic stellate
cells (PSCs) are critical for PDAC metabolism through the secretion of non
essential amino acids (NEAA). Specifically, we uncover a previously undescribed
role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC
to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis.
This shift in fuel source decreases the tumour's dependence on glucose and serum
derived nutrients, which are limited in the pancreatic tumour microenvironment.
Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC
autophagy, a process that is stimulated by cancer cells. Thus, our results
demonstrate a novel metabolic interaction between PSCs and cancer cells, in which
PSC-derived alanine acts as an alternative carbon source. This finding highlights
a previously unappreciated metabolic network within pancreatic tumours in which
diverse fuel sources are used to promote growth in an austere tumour
microenvironment.
PMID- 27509859
TI - Compression and ablation of the photo-irradiated molecular cloud the Orion Bar.
AB - The Orion Bar is the archetypal edge-on molecular cloud surface illuminated by
strong ultraviolet radiation from nearby massive stars. Our relative closeness to
the Orion nebula (about 1,350 light years away from Earth) means that we can
study the effects of stellar feedback on the parental cloud in detail. Visible
light observations of the Orion Bar show that the transition between the hot
ionized gas and the warm neutral atomic gas (the ionization front) is spatially
well separated from the transition between atomic and molecular gas (the
dissociation front), by about 15 arcseconds or 6,200 astronomical units (one
astronomical unit is the Earth-Sun distance). Static equilibrium models used to
interpret previous far-infrared and radio observations of the neutral gas in the
Orion Bar (typically at 10-20 arcsecond resolution) predict an inhomogeneous
cloud structure comprised of dense clumps embedded in a lower-density extended
gas component. Here we report one-arcsecond-resolution millimetre-wave images
that allow us to resolve the molecular cloud surface. In contrast to stationary
model predictions, there is no appreciable offset between the peak of the H2
vibrational emission (delineating the H/H2 transition) and the edge of the
observed CO and HCO+ emission. This implies that the H/H2 and C+/C/CO transition
zones are very close. We find a fragmented ridge of high-density substructures,
photoablative gas flows and instabilities at the molecular cloud surface. The
results suggest that the cloud edge has been compressed by a high-pressure wave
that is moving into the molecular cloud, demonstrating that dynamical and non
equilibrium effects are important for the cloud evolution.
PMID- 27509860
TI - Ancient DNA: Muddy messages about American migration.
PMID- 27509862
TI - Cancer metabolism: Friendly neighbours feed tumour cells.
PMID- 27509861
TI - Molecular basis of APC/C regulation by the spindle assembly checkpoint.
AB - In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures
that each daughter cell inherits an identical set of chromosomes. The SAC
coordinates the correct attachment of sister chromatid kinetochores to the
mitotic spindle with activation of the anaphase-promoting complex (APC/C), the E3
ubiquitin ligase responsible for initiating chromosome separation. In response to
unattached kinetochores, the SAC generates the mitotic checkpoint complex (MCC),
which inhibits the APC/C and delays chromosome segregation. By cryo-electron
microscopy, here we determine the near-atomic resolution structure of a human
APC/C-MCC complex (APC/C(MCC)). Degron-like sequences of the MCC subunit BubR1
block degron recognition sites on Cdc20, the APC/C coactivator subunit
responsible for substrate interactions. BubR1 also obstructs binding of the
initiating E2 enzyme UbcH10 to repress APC/C ubiquitination activity.
Conformational variability of the complex enables UbcH10 association, and
structural analysis shows how the Cdc20 subunit intrinsic to the MCC (Cdc20(MCC))
is ubiquitinated, a process that results in APC/C reactivation when the SAC is
silenced.
PMID- 27509864
TI - Comprehensive two-dimensional liquid chromatography for polyphenol analysis in
foodstuffs.
AB - Polyphenols are a class of plant secondary metabolites that are recently drawing
a special interest because of their broad spectrum of pharmacological effects. As
they are characterized by an enormous structural variability, the identification
of these molecules in food samples is a difficult task, and sometimes having only
a limited number of commercially available reference materials is not of great
help. One-dimensional liquid chromatography is the most widely applied analytical
approach for their analysis. In particular, the hyphenation of liquid
chromatography to mass spectrometry has come to play an influential role by
allowing relatively fast tentative identification and accurate quantification of
polyphenolic compounds at trace levels in vegetable media. However, when dealing
with very complex real-world food samples, a single separation system often does
not provide sufficient resolving power for attaining rewarding results.
Comprehensive two-dimensional liquid chromatography is a technique of great
analytical impact, since it offers much higher peak capacities than separations
in a single dimension. In the present review, we describe applications in the
field of comprehensive two-dimensional liquid chromatography for polyphenol
analysis in real-world food samples. Comprehensive two-dimensional liquid
chromatography applications to nonfood matrices fall outside the scope of the
current report and will not be discussed.
PMID- 27509863
TI - Capturing a substrate in an activated RING E3/E2-SUMO complex.
AB - Post-translational protein modification by ubiquitin (Ub) and ubiquitin-like
(Ubl) proteins such as small ubiquitin-like modifier (SUMO) regulates processes
including protein homeostasis, the DNA damage response, and the cell cycle.
Proliferating cell nuclear antigen (PCNA) is modified by Ub or poly-Ub at lysine
(Lys)164 after DNA damage to recruit repair factors. Yeast PCNA is modified by
SUMO on Lys164 and Lys127 during S-phase to recruit the anti-recombinogenic
helicase Srs2. Lys164 modification requires specialized E2/E3 enzyme pairs for
SUMO or Ub conjugation. For SUMO, Lys164 modification is strictly dependent on
the E3 ligase Siz1, suggesting the E3 alters E2 specificity to promote Lys164
modification. The structural basis for substrate interactions in activated E3/E2
Ub/Ubl complexes remains unclear. Here we report an engineered E2 protein and
cross-linking strategies that trap an E3/E2-Ubl/substrate complex for structure
determination, illustrating how an E3 can bypass E2 specificity to force-feed a
substrate lysine into the E2 active site.
PMID- 27509865
TI - HER2-targeted antibody drug conjugates for ovarian cancer therapy.
AB - HER2 targeted delivery of ovarian cancer therapy has been beneficial for some
patients, although, its efficacy is yet to be confirmed in large populations. We
generated a novel anti-HER2 humanized antibody (Hertuzumab) and conjugated it to
a microtubule-disrupting drug monomethyl auristatin E conjugate (MMAE) with a
lysosomal protease-cleavable valine-citrulline linker. The average drug to
antibody ratio (DAR) of Hertuzumab-vc-MMAE was varied by conjugating Hertuzumab
antibodies with increasing linker-drugs (LDs) from D0-D8. The resulting
conjugates were tested for kinetic affinity for soluble HER2-ECD, cytotoxicity,
and in vivo pharmacokinetics. The kinetic binding constant values (KD) were
obtained by the bio-layer interference (BLI) method. The half time (t1/2) and
clearance (Cl) results of the pharmacokinetic profile in rats were DAR-dependent.
Hertuzumab-vc-MMAE with DAR4 was selected for further evaluation. Both Hertuzumab
and Hertuzumab conjugates could bind to HER2 antigen, and exhibited significant
cytotoxicity on HER2 positive tumor cells after internalization by receptor
mediated endocytosis. Hence, Hertuzumab-vc-MMAE conjugates were significantly
selective both in vitro and in vivo as compared to other ovarian cancer clinical
therapies that are currently used. Cell signal transduction and cell cycle were
also affected, as shown by down regulation of PI3K/AKT pathway and arrested
mitosis in the G2/M phase. The pharmacokinetics and pharmacodynamics (PK-PD) of
the conjugates in nude mouse xenograft model demonstrated a correlation between
efficacy and drug concentration. These results show that Hertuzumab-vc-MMAE is a
potential therapeutic agent for HER2 positive ovarian cancer.
PMID- 27509866
TI - Neurotensin-based hybrid peptide's anti-inflammatory activity in murine model of
a contact sensitivity response.
AB - The objective of the study was to investigate the possibility of modulation of
skin inflammation by topical treatment with a novel compound: an opioid
neurotensin hybrid peptide PK20 encompassing endomorphin-2 analog and modified
fragment of neurotensin (8-13). Contact sensitivity response was induced in mice
by skin sensitization with dinitrofluorobenzene (DNFB) followed by topical hapten
application on ears. Mice were treated locally with PK20 or pure cream 2h after
the challenge with DNFB. 2 and 24h after hapten exposure, ear thickness was
determined. Ears were collected for histology and homogenization. Supernatants
were used for measurement of contents of cytokines and lipid peroxidation
products. Treatment with PK20 reduced significantly the late phase of contact
sensitivity response, which was revealed by ear thickness diminution and
reduction of inflammatory cell infiltration. The average concentrations of IL
1alpha, MCP-1, TNF-alpha and thiobarbituric acid-reactive substances were
significantly decreased in the ears treated with the chimera in comparison to the
control cream treated ears in DNFB sensitized/DNFB challenged group. We found
that PK20 topical treatment alleviates hypersensitivity responses triggered by
DNFB challenge and usage of the hybrid peptide may be a novel therapeutic
strategy in the treatment of chronic inflammatory diseases. However, the
mechanism remains unclear and needs further investigation.
PMID- 27509868
TI - Nanoparticles assembled via pH-responsive reversible segregation of cyclodextrins
in polyrotaxanes.
AB - Supramolecular polymers with monomers bound together by secondary interactions,
such as polyrotaxanes (PRXs), consisting of alpha cyclodextrin (alphaCD) threaded
onto poly(ethylene glycol) (PEG), have attracted interest as a result of their
ability to overcome physical limitations present in conventional, covalently
structured polymers. Herein, we describe the formation of pH-responsive
supramolecular assemblies from carboxyethylester bearing alphaCD and PEG PRXs.
These PRXs were formed using PEG of Mw 20 kDa and a threading degree of 28%. Upon
charge neutralisation the threaded alphaCDs co-localise, resulting in aggregation
of the PRXs and the formation of a suspension by self-assembly. This process is
shown to be reversible and possible via the mobility of CDs along the PEG guest
chain. As a result of the inherent properties of PRXs, such as enhanced
multivalent interactions and degradation, these responsive supramolecular
polymers are expected to be of interest in fields where PRX-based materials have
already found application, including paints, self-healing materials, surface
coatings, and polymer therapeutics.
PMID- 27509867
TI - Impact of statin therapy on plasma leptin concentrations: a systematic review and
meta-analysis of randomized placebo-controlled trials.
AB - OBJECTIVES: The effects of statins on insulin sensitivity, metabolic homeostasis
and adipokines in humans are controversial. Several studies have investigated the
impact of statin therapy on plasma leptin concentrations but the results have
been inconsistent. The aim of the present study was to conduct a systematic
review and meta-analysis of available evidence to calculate the effect size of
statin therapy in changing serum leptin concentrations. METHODS: A systematic
search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was
performed to identify randomized placebo-controlled trials investigating the
effect of statins on plasma leptin concentrations. A random-effects model and
generic inverse variance method were used for meta-analysis. Sensitivity
analysis, risk-of-bias evaluation and publication bias assessment were carried
out using standard methods. Random-effects meta-regression was used to evaluate
the impact of treatment duration on the estimated effect size. RESULTS: Six
trials, with a total of 425 subjects, met the eligibility criteria. Overall,
statin therapy had no significant effect on leptin levels (weighted mean
difference -0.32 ng ml-1 , 95% confidence nterval: -2.94, 2.30, P = 0.813). This
effect was robust in the sensitivity analysis and in subgroup analyses of trials
with <12 or >=12 weeks' duration. There was no association between the duration
of statin therapy and changes in plasma leptin levels. Furthermore, there was no
differential effect of hydrophilic and lipophilic statins on plasma leptin
concentrations. CONCLUSION: Unless more consistent evidence becomes available in
the future, the hypothesis of a relationship between statin use and serum leptin
concentrations seem to be unfounded.
PMID- 27509869
TI - Measuring policy and related effects of a health impact assessment related to
connectivity.
AB - Health Impact Assessments are an important tool to help policymakers perceive the
potential positive and negative contributions of decisions to public health.
While they have been increasingly used in the United States, studies have not
examined intermediate effects. Using key stakeholder interviews, this manuscript
examines policy outcomes and other related effects of the HIA 21months after
completing a Health Impact Assessment Report around connectivity policy. Further,
it reflects on the measurement of these effects as part of the monitoring and
evaluation stage of the Health Impact Assessment process.
PMID- 27509870
TI - The neurobiological and behavioral overlaps of nicotine and food addiction.
AB - Both cigarette smoking and obesity are significant public health concerns and are
associated with increased risk of early mortality. It is well established that
the mesolimbic dopamine pathway is an important component of the reward system
within the brain and is implicated in the development of addiction. Indeed,
nicotine and highly palatable foods are capable of altering dopamine release
within this system, engendering addictive like responses in susceptible
individuals. Although additional research is warranted, findings from animal and
human literature have elucidated many of neuroadaptions that occur from exposure
to nicotine and highly palatable foods, leading to a greater understanding of the
underlying mechanisms contributing to these aberrant behaviors. In this review we
present the findings taken from preclinical and clinical literature of the known
effects of exposure to nicotine and highly palatable foods on the reward related
circuitry within the brain. Further, we compare the neurobiological and
behavioral overlaps between nicotine, highly palatable foods and obesity. Lastly,
we examine the stigma associated with smoking, obesity and food addiction, and
the consequences stigma has on the overall health and wellbeing of an individual.
PMID- 27509871
TI - Reality-check in physical activity promotion: Self-report-based guidelines vs.
measurement-based estimates.
PMID- 27509872
TI - Can maternal-fetal hemodynamics influence prenatal development in dogs?
AB - The goals of this study were to report embryonic and fetal ultrasound changes and
compare blood flow of uteroplacental and umbilical arteries of normal and
abnormal conceptus. Accordingly, from the day of mating or artificial
insemination, all fetuses in 60 pregnancies were evaluated weekly. According to
the ultrasound findings, the gestational age was determined and the conceptuses
were divided into normal or abnormal (embryonic and fetal abnormalities). The two
dimensional ultrasound assessment consists of measuring and evaluating the
echogenicity of conceptus and extra-fetal structures. Doppler velocimetry
measured the resistivity index (RI) and pulsatility index (PI) of uteroplacental
and umbilical arteries. Two-dimensional and Doppler measurements were expressed
as mean and standard deviation. Differences between normal and abnormal groups
were subject to Mann-Whitney test (P<0.05). Of 264 fetuses, 15.90% showed
embryonic abnormalities (resorption) and 5.68% presented fetal abnormalities
(congenital abnormalities, fetal underdevelopment and fetal death). We observed a
reduced diameter and abnormalities in the contour of gestational vesicle, lack of
viability, increased placental thickness, increased fluid echogenicity and
increases in RI and PI of uteroplacental arteries of conceptuses with embryonic
resorption between the 2nd and 4th weeks. Fetuses with abnormalities showed
changes in the flow of uteroplacental and umbilical arteries prior to
visualization of two-dimensional alterations and different vascular behavior
according to the classification of the change. Results show that ultrasound is
efficient for the detection of embryonic and fetal abnormalities. When combined
with Doppler ultrasound, it allows early detection of gestational changes, as
well as hemodynamic changes, in conceptuses with abnormalities, which may
influence their development.
PMID- 27509873
TI - Cryopreservation of bull semen: Evolution from egg yolk based to soybean based
extenders.
AB - Since the inception of bovine semen cryopreservation, egg yolk and milk based
extenders have been used to protect sperm from the detrimental effects of cooling
and freezing. In recent years, demand for alternatives to conventional commercial
extenders has arisen as the risk of introducing exotic diseases through
transporting egg yolk based products has been recognized. Egg yolk can also
interfere with sperm evaluation and the presence of particulate material in the
extender may reduce fertility. Soybeans contain lecithin, a phospholipid fraction
that can substitute for high molecular weight lipoprotein and phospholipids from
egg yolk and prevent or ameliorate damage to the sperm plasma membrane that
occurs during extension, cooling, and cryopreservation. Soy lecithin based
extenders have been evaluated for processing and freezing bovine semen, although
extender from soybean milk has not been studied as extensively. Commercially
available soy lecithin based extenders are used increasingly but remain under
scrutiny and are not universally accepted. With these observations in mind, this
review is intended to examine effects of conventional cryopreservation
procedures, methods of assessment, and potential for developing soybean extract
as an acceptable alternative to traditional egg yolk and milk based extenders for
bull sperm cryopreservation.
PMID- 27509874
TI - Effect of dietary supplementation with amino acids on boar sperm quality and
fertility.
AB - The aim of this study was to evaluate the effects of dietary supplementation with
amino acids on sperm quality and fertility rates after insemination with boar
semen. Twelve Yorkshire boars were paired by age and allocated to one of two
dietary treatments composed of total lysine levels of 0.64% (T1) and 0.96% (T2),
with the lysine: methionine: threonine: tryptophan: valine ratio in the diets set
to 100:27:73:19:69 through the addition of synthetic amino acids. Semen was
collected twice weekly (phase 1, 1-12 wk); every other day (phase 2, 13-16 wk);
twice weekly (phase 3, 17-26 wk); and daily (phase 4, 27-28 wk). Semen was
collected from boars during phase 3 and used to inseminate 64 multiparous sows.
Our results showed that sperm concentration and total sperm cells were greater in
boars in T2 than in boars in T1 in phases 2 and 4 (P<0.05). Sperm motility
parameters, morphologically normal sperm, and acrosome integrity in T2 boars were
greater than those in T1 boars (P<0.05) during the experiment. Free amino acid
concentrations in seminal plasma increased in T2 boars (P<0.05). Furthermore,
sows inseminated with semen collected from T2 boars gave birth to more live
piglets than those inseminated with semen collected from T1 boars (P=0.04). In
conclusion, supplementation of boar diet with amino acids improves sperm quality,
and subsequently increases fertilization capacity and the number of live piglets.
PMID- 27509876
TI - Influence of sustained deworming pressure on the anthelmintic resistance status
in strongyles of sheep under field conditions.
AB - Anthelmintic resistance (AR) status in Madras Red sheep from selected field
flocks of a government funded scheme, covered by regular, sustained anthelmintic
treatment for more than 10 years was determined. Parameters such as fecal egg
count reduction test (FECRT), larval paralysis assay (LPA), and allele-specific
PCR (AS-PCR) were used to test the efficacy of fenbendazole, tetramisole, and
ivermectin at recommended doses, in two seasons. Sheep belonging to non
beneficiary farmers were used as controls. Mean FECRT values of beneficiary group
during winter and summer seasons were 77.77 and 76.04, 93.65 and 92.12, and 95.37
and 98.06 %, respectively, for fenbendazole, tetramisole, and ivermectin. In the
non-beneficiary groups, the corresponding values were 74.82 and 81.09 %, 96.05
and 97.40 %, and 97.26 and 98.23 %, respectively. The results revealed resistance
to fenbendazole, suspect resistance to tetramisole and susceptibility to
ivermectin in beneficiary flock. In non-beneficiary flock, while resistance was
noticed against fenbendazole, both tetramisole and ivermectin were effective.
FECR values were found to be significantly different between beneficiary and non
beneficiary groups against tetramisole. The results of LPA confirmed this
finding, as 50 % of the Haemonchus contortus larvae were paralyzed at the
concentration of 0.0156 MUg/ml in the beneficiary group, while those of non
beneficiary groups required lower concentrations of 0.0078 MUg/ml. AS-PCR
revealed the predominance of heterozygous susceptible population of H. contortus
in the beneficiary group. In this study, resistance to fenbendazole was confirmed
in both the beneficiary and non-beneficiary groups and this could be attributed
to frequent use of benzimidazoles as seen from the deworming records. Emergence
of tetramisole resistance was detected in the beneficiary group, where the drug
was used continuously for 4 years. Ivermectin was found to be effective in all
the flocks. It is recommended that the practice of routine deworming of three to
four times a year should be avoided, as it can lead to emergence of anthelmintic
resistance.
PMID- 27509875
TI - Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer's
disease in rodent models.
AB - Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase-1 (COX-1)
and COX-2 enzymes. The NLRP3 inflammasome is a multi-protein complex responsible
for the processing of the proinflammatory cytokine interleukin-1beta and is
implicated in many inflammatory diseases. Here we show that several clinically
approved and widely used NSAIDs of the fenamate class are effective and selective
inhibitors of the NLRP3 inflammasome via inhibition of the volume-regulated anion
channel in macrophages, independently of COX enzymes. Flufenamic acid and
mefenamic acid are efficacious in NLRP3-dependent rodent models of inflammation
in air pouch and peritoneum. We also show therapeutic effects of fenamates using
a model of amyloid beta induced memory loss and a transgenic mouse model of
Alzheimer's disease. These data suggest that fenamate NSAIDs could be repurposed
as NLRP3 inflammasome inhibitors and Alzheimer's disease therapeutics.
PMID- 27509877
TI - Seroprevalence and risk factors of bovine viral diarrhoea virus (BVDV) infection
in yaks (Bos grunniens) in northwest China.
AB - Bovine viral diarrhoea virus (BVDV), a member of the Pestivirus genus, is an
important pathogen of cattle worldwide, causing reproductive disorders in adult
cattle and mucosal disease in calves. However, limited information about BVDV
infection in yaks (Bos grunniens) in China is available, especially in white yaks
which is a unique yak breed that only lives in Tianzhu Tibetan Autonomous County
(TTAC), Gansu Province, northwest China. Therefore, we conducted a cross
sectional study to estimate the seroprevalence and risk factors associated with
BVDV infection in 1584 yaks in Gansu province, northwest China, between April
2013 and March 2014 using an indirect ELISA test. The overall seroprevalence of
BVDV in yaks was 37.56 % (595/1584), with 45.08 % (275/610) in black yaks and
32.85 % (320/974) in white yaks. Moreover, positive yaks were found in all four
regions, varied from 33.22 to 40.31 %. Male yaks had a similar seroprevalence
(37.84 %) with that of the female yaks (37.11 %). Season, species and
geographical origins of yaks were considered as risk factors analyzed by logistic
regression model. To our knowledge, this is the first report of seroprevalence
and risk factors associated with BVDV infection in white yaks in China.
PMID- 27509878
TI - Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway
causing human bladder relaxation through H2S production.
AB - The urothelium modulates detrusor activity through releasing factors whose nature
has not been clearly defined. Here we have investigated the involvement of H2S as
possible mediator released downstream following muscarinic (M) activation, by
using human bladder and urothelial T24 cell line. Carbachol stimulation enhances
H2S production and in turn cGMP in human urothelium or in T24 cells. This effect
is reversed by cysthationine-beta-synthase (CBS) inhibition. The blockade of M1
and M3 receptors reverses the increase in H2S production in human urothelium. In
T24 cells, the blockade of M1 receptor significantly reduces carbachol-induced
H2S production. In the functional studies, the urothelium removal from human
bladder strips leads to an increase in carbachol-induced contraction that is
mimicked by CBS inhibition. Instead, the CSE blockade does not significantly
affect carbachol-induced contraction. The increase in H2S production and in turn
of cGMP is driven by CBS-cGMP/PKG-dependent phosphorylation at Ser(227) following
carbachol stimulation. The finding of the presence of this crosstalk between the
cGMP/PKG and H2S pathway downstream to the M1/M3 receptor in the human urothelium
further implies a key role for H2S in bladder physiopathology. Thus, the
modulation of the H2S pathway can represent a feasible therapeutic target to
develop drugs for bladder disorders.
PMID- 27509879
TI - Isaacs' syndrome and Hodgkin lymphoma: a rare association.
PMID- 27509880
TI - Combination of the histone deacetylase inhibitor depsipeptide and 5-fluorouracil
upregulates major histocompatibility complex class II and p21 genes and activates
caspase-3/7 in human colon cancer HCT-116 cells.
AB - Epigenetic anticancer drugs such as histone deacetylase (HDAC) inhibitors have
been combined with existing anticancer drugs for synergistic or additive effects.
In the present study, we found that a very low concentration of depsipeptide, an
HDAC inhibitor, potentiated the antitumor activity of 5-fluorouracil (5-FU) in a
human colon cancer cell model using HCT-116, HT29, and SW48 cells via the
inhibition of colony formation ability or cellular viability. Exposure to a
combination of 5-FU (1.75 uM) and 1 nM depsipeptide for 24 and 48 h resulted in a
3- to 4-fold increase in activated caspase-3/7, while 5-FU alone failed to
activate caspase-3/7. Microarray and subsequent gene ontology analyses revealed
that compared to 5-FU or depsipeptide alone, the combination treatment of 5-FU
and depsipeptide upregulated genes related to cell death and the apoptotic
process consistent with the inhibition of colony formation and caspase-3/7
activation. These analyses indicated marked upregulation of antigen processing
and presentation of peptide or polysaccharide antigen via major
histocompatibility complex (MHC) class (GO:0002504) and MHC protein complex
(GO:0042611). Compared with vehicle controls, the cells treated with the
combination of 5-FU and depsipeptide showed marked induction (3- to 8.5-fold) of
expression of MHC class II genes, but not of MHC class I genes. Furthermore, our
global analysis of gene expression, which was focused on genes involved in the
molecular regulation of MHC class II genes, showed enhancement of pro-apoptotic
PCAF and CIITA after the combination of 5-FU and depsipeptide. These results may
indicate a closer relationship between elevation of MHC class II expression and
cellular apoptosis induced by the combination of depsipeptide and 5-FU. To the
best of our knowledge, this is the first study to report that the combination of
5-FU and depsipeptide induces human colon cancer cell apoptosis in a concerted
manner with the induction of MHC class II gene expression.
PMID- 27509881
TI - Long-term Outcome of an Organ Preservation Program After Neoadjuvant Treatment
for Rectal Cancer.
AB - BACKGROUND: The aim of this study was to establish the oncological and functional
results of organ preservation with a watch-and-wait approach (W&W) and selective
transanal endoscopic microsurgery (TEM) in patients with a clinical complete or
near-complete response (cCR) after neoadjuvant chemoradiation for rectal cancer.
METHODS: Between 2004 and 2014, organ preservation was offered if response
assessment with digital rectal examination, endoscopy, and MRI showed (near) cCR.
Watch-and-wait was offered for cCR, and two options were offered for near cCR:
TEM or reassessment after three months. Follow-up included endoscopy and MRIs
every three months during the first year, and every six months thereafter. Long
term outcome was assessed with Kaplan-Meier curves. Functional outcome was
assessed with colostomy-free survival and Vaizey incontinence score (0 = perfect
continence, 24 = totally incontinent). RESULTS: One hundred patients were
included, with median follow-up of 41.1 months. Sixty-one had cCR at initial
response assessment. Thirty-nine had near cCR, of whom 24 developed cCR at the
second assessment and 15 patients underwent TEM (9 ypT0, 1 ypT1, 5 ypT2). Fifteen
patients developed a local regrowth (12 luminal, 3 nodal), all salvageable and
within 25 months. Five patients developed metastases, and five patients died.
Three-year overall survival was 96.6% (95% confidence interval [CI] = 89.9% to
98.9%), distant metastasis-free survival was 96.8% (95% CI = 90.4% to 99.0%),
local regrowth-free survival was 84.6% (95% CI = 75.8% to 90.5%), and disease
free survival was 80.6% (95% CI = 70.9% to 87.4%). Colostomy-free survival was
94.8% (95% CI = 88.0% to 97.8%), with a good continence after watch-and-wait
(Vaizey = 3.4, SD = 3.9) and moderate after TEM (Vaizey = 9.7, SD = 5.1).
CONCLUSIONS: Organ preservation appears oncologically safe for selected rectal
cancer patients with a cCR or near cCR after neoadjuvant chemoradiation when
applying strict selection criteria and frequent follow-up, including endoscopy
and MRI. The low colostomy rate and the good long-term functional outcome warrant
discussing this option with the patient as an alternative to major surgery.
PMID- 27509882
TI - Contrary microRNA Expression Pattern Between Fetal and Adult Cardiac Remodeling:
Therapeutic Value for Heart Failure.
AB - microRNAs (miRNAs) belong to a class of non-coding RNAs that regulate post
transcriptional gene expression during development and disease. Growing evidence
indicates abundant miRNA expression changes and their important role in cardiac
hypertrophy and failure. However, the role of miRNAs in fetal cardiac remodeling
is little known. Here, we investigated the altered expression of fifteen miRNAs
in rat fetal cardiac remodeling compared with adult cardiac remodeling. Among
fifteen tested miRNAs, eleven and five miRNAs (miR-199a-5p, miR-214-3p, miR-155
3p, miR-155-5p and miR-499-5p) are significantly differentially expressed in
fetal and adult cardiac remodeling, respectively. After comparison of miRNA
expression in fetal and adult cardiac remodeling, we find that miRNA expression
returns to the fetal level in adult cardiac failure and is activated in advance
of the adult level in fetal failure. The current study highlights the contrary
expression pattern between fetal and adult cardiac remodeling and that supports a
novel potential therapeutic approach to treating heart failure.
PMID- 27509883
TI - Simultaneous application of two independent EIT devices for real-time multi-plane
imaging.
AB - Diagnosis and treatment of many lung diseases like cystic fibrosis (CF) or
chronic obstructive pulmonary disease (COPD) could benefit from 3D ventilation
information. Applying two EIT systems concurrently is a simple approach without
specialized hardware that allows monitoring of regional changes of ventilation
distribution inside the thorax at different planes with the high temporal
resolution much valued in common single plane EIT. Effects of two simultaneously
operated EIT devices on one subject were investigated to monitor rapid processes
inside the thorax with a multi-plane approach. Results obtained by simulations
with a virtual phantom and measurements with a phantom tank reveal that the
distance of electrode planes has an important influence on the signal quality.
Band-pass filters adapted according to the distance of the planes, can be used to
reduce the crosstalk of the concurrent EIT systems. Besides simulations and
phantom tank experiments measurements were also taken from a lung healthy
volunteer to demonstrate the operation under realistic conditions. Reconstructed
images indicate that it is possible to simultaneously visualize regional
ventilation at different planes if settings of the EIT devices are chosen
appropriately.
PMID- 27509884
TI - Identification of distinct genes associated with seawater aspiration-induced
acute lung injury by gene expression profile analysis.
AB - Seawater aspiration-induced acute lung injury (ALI) is a syndrome associated with
a high mortality rate, which is characterized by severe hypoxemia, pulmonary
edema and inflammation. The present study is the first, to the best of our
knowledge, to analyze gene expression profiles from a rat model of seawater
aspiration-induced ALI. Adult male Sprague-Dawley rats were instilled with
seawater (4 ml/kg) in the seawater aspiration-induced ALI group (S group) or with
distilled water (4 ml/kg) in the distilled water negative control group (D
group). In the blank control group (C group) the rats' tracheae were exposed
without instillation. Subsequently, lung samples were examined by histopathology;
total protein concentration was detected in bronchoalveolar lavage fluid (BALF);
lung wet/dry weight ratios were determined; and transcript expression was
detected by gene sequencing analysis. The results demonstrated that
histopathological alterations, pulmonary edema and total protein concentrations
in BALF were increased in the S group compared with in the D group. Analysis of
differential gene expression identified up and downregulated genes in the S group
compared with in the D and C groups. A gene ontology analysis of the differential
gene expression revealed enrichment of genes in the functional pathways
associated with neutrophil chemotaxis, immune and defense responses, and cytokine
activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the
cytokine-cytokine receptor interaction pathway was one of the most important
pathways involved in seawater aspiration-induced ALI. In conclusion, activation
of the cytokine-cytokine receptor interaction pathway may have an essential role
in the progression of seawater aspiration-induced ALI, and the downregulation of
tumor necrosis factor superfamily member 10 may enhance inflammation.
Furthermore, IL-6 may be considered a biomarker in seawater aspiration-induced
ALI.
PMID- 27509885
TI - Magnetic force-assisted self-locking metallic bead array for fabrication of
diverse concave microwell geometries.
AB - Spheroid cell culture is very useful for further understanding cellular behavior
including motility and biochemical reaction since it mimics three-dimensional
(3D) in vivo organ tissue. Among previously proposed various methods for spheroid
production, such as hanging drop and spinner flask, microwell is a recently
developed method harnessing microtechnology to produce uniform-sized spheroids.
Although soft-lithography has been popular for creating microwell arrays, a 3D
spherical geometry has been regarded as difficult to fabricate using conventional
methods, or often requires complex fabrication processes and expensive equipment.
Here, we propose a new method for fabricating concave microwells for cell
spheroid production and culture. To demonstrate this method, we fabricated a 30 *
30 microwell array in 3 * 3 cm plates, utilizing metal beads, a through-hole
array, and an assembly of small magnets. The spherical metal beads were used as a
mold for the microwell, naturally creating the desired 3D concave microwell
geometry. One of the key ideas was to place and hold each metal bead in the
designated through-hole using the small magnet array. We also performed
computational simulation of the magnetostatic force to design and observe the
magnetic force field in detail. In addition, to provide a practical demonstration
of the proposed system in cell biology, we created and cultured adipose-derived
stem cell spheroids for 14 days for chondrogenic differentiation. This method
allows further variations in microwell geometry that will enhance the method's
applicability as a helpful tool for various studies in cell biology, cancer
research, and tissue engineering.
PMID- 27509886
TI - Photolabile acetals as profragrances: the effect of structural modifications on
the light-induced release of volatile aldehydes on cotton.
AB - Because volatile compounds evaporate from surfaces that are usually exposed to
daylight, photoresponsive delivery systems are particularly suitable to control
their release. In the present study, we investigated 4,4-diphenyl-4H
benzo[d][1,3]dioxins as profragrances for the light-induced delivery of aldehydes
in functional perfumery. The efficiency of fragrance release was investigated on
cotton after direct and indirect surface deposition from a fabric softening
formulation as a function of the substitution pattern of the profragrance
structure. Dynamic headspace analysis above the cotton surface demonstrated that
the structure of the profragrance had a much larger effect on the fragrance
release than did the amount of deposition on the target surface. Although some
trends observed for the photolysis in solution also applied to the reaction on
cotton, it is not generally possible to predict the photochemical behaviour of
structurally different precursors on surfaces from their solution properties. The
fact that the present system performed on a dry surface makes it an interesting
light-triggered delivery vehicle for other classes of bioactive volatile
compounds, such as pheromones or agrochemicals.
PMID- 27509888
TI - Effective Atom-Molecule Conversions Using Radio Frequency Fields.
AB - The present study is inspired by the Wieman group experiment [Phys. Rev. Lett.
2005, 95, 190404], in which they use a slow modulated magnetic field to
effectively transfer rubidium atoms into cold molecules near a Feshbach
resonance. We develop a time-dependent collision theory based on two channel
model potentials to study the atom-molecule population transfer induced by a
single-color radio frequency field in an ultracold 87 Rb gas. Wave-packet
dynamical simulations allow an investigation of both bound-bound transitions and
free-bound transitions. The effects of temperature, detuning and the RF amplitude
on the population transfer are discussed in detail. Some of our simulations
suggest that oscillatory atom-molecule conversion could originate from the long
coherence time of the wave packet. This coherence time is unusually long in
ultracold gases because the collision energy is typically quite well-defined.
PMID- 27509889
TI - Comparative Study Using 100-300 Versus 300-500 MUm Microspheres for Symptomatic
Patients Due to Enlarged-BPH Prostates.
AB - PURPOSE: The purpose of the study was to compare safety and efficacy outcomes
following prostate artery embolization (PAE) for the treatment of lower urinary
tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with 100-300
versus 300-500 MUm tris-acryl gelatin microspheres. MATERIALS AND METHODS:
Patients were prospectively treated between August 2011 and June 2013 to receive
PAE with 100-300 MUm (group A) or 300-500 MUm (group B) tris-acryl gelatin
microspheres. Patients were followed for a minimum of 12 months and were assessed
for changes in International Prostate Symptom Score (IPSS), quality of life (QoL)
index, prostate volume determined by magnetic resonance imaging, serum prostate
specific antigen (PSA), and maximum urine flow rate (Qmax), as well as any
treatment-related adverse events. RESULTS: Fifteen patients were included in each
group, and PAE was technically successful in all cases. Both groups experienced
significant improvement in mean IPSS, QoL, prostate volume, PSA, and Qmax (p <
0.05 for all). The differences observed between the two groups included a
marginally insignificant more adverse events (p = 0.066) and greater mean serum
PSA reduction at 3 months of follow-up (p = 0.056) in group A. CONCLUSIONS: Both
100-300 and 300-500 MUm microspheres are safe and effective embolic agents for
PAE to treat LUTS-related to BPH. Although functional and imaging outcomes did
not differ significantly following use of the two embolic sizes, the greater
incidence of adverse events with 100-300 MUm microspheres suggests that 300-500
MUm embolic materials may be more appropriate.
PMID- 27509887
TI - Gastroenterologists' Perceptions Regarding Ulcerative Colitis and Its Management:
Results from a Large-Scale Survey.
AB - INTRODUCTION: Misperceptions about ulcerative colitis (UC) may influence
management strategies and limit opportunities for improving patient outcomes.
This study assessed physicians' perceptions of UC, concepts of disease severity
and remission, and treatment goals. METHODS: Gastroenterologists who typically
treated >=10 adults with UC per month were recruited for a large-scale, web-based
survey. Participants were asked about their perceptions of UC (often vs. Crohn's
disease [CD]), treatment goals, and medication use. Response data were evaluated
via descriptive statistics and univariate and multivariable analyses. RESULTS:
Gastroenterologists (N = 500) with a mean of 16.5 years (standard deviation, 8.7
years) in practice participated. In comparison to CD, survey respondents
perceived UC as being easier to diagnose, having better treatment outcomes, and
being associated with later prescribing of biologics. Treatment goals commonly
considered to have the greatest importance included quality of life improvement
(31.2% of respondents), maintenance of clinical remission (17.4%), and mucosal
healing (17.4%). When respondents evaluated the performance of medication classes
in achieving these goals, biologics were rated significantly higher than all
other classes (P < 0.05). However, the most common drivers for the initiation of
biologic therapy were the development of steroid refractoriness (66.8%) and
steroid dependency (65.8%). Medication class use by UC severity was generally
consistent with the traditional step-up approach to UC therapy, with biologics
being used most commonly for severe UC. CONCLUSION: These results suggest a
possible disparity between treatment goals and therapeutic management in UC. An
increased awareness of general UC perceptions is an important step toward a
better overall understanding of the disease and, ultimately, toward improved
management aligned with treatment goals. FUNDING: This study was sponsored by the
American Gastroenterological Association (AGA), and the design and conduct of the
study as well as article processing charges and the open access fee for this
publication were funded by Takeda Pharmaceuticals International, Inc. (TPI).
PMID- 27509890
TI - Effects of different training histories upon manufacturing a tool to solve a
problem: insight in capuchin monkeys (Sapajus spp.).
AB - The emergence of novel behavior is a multilayered phenomenon that comprehends
distinct processes. One such process is known as insightful problem solving.
"Insight" can be explained as the spontaneous interconnection of previously
acquired behavioral repertoires. The objective of this study was to investigate:
(1) whether capuchin monkeys (Sapajus spp.) do show the interconnection of
repertoires, and (2) whether different performances of problem solving could be
produced by different training histories. Two repertoires were independently
trained: (a) joining two pieces of a tool to manufacture a new tool and (b)
raking food with one tool. In the test situation, food was out of reach, and two
joinable pieces of a tool, different from the ones used in training, were
presented. To solve the problem, the monkeys had to join the two pieces and rake
the food with the new manufactured tool. In Experiment 1, one monkey received
symmetric training (equal number of sessions) of both repertoires and solved the
task, but not in an insightful manner. In Experiment 2, six monkeys were divided
into two groups: one group received symmetric training, and the second group had
asymmetrical training of the repertoires (unequal number of sessions). Subjects
from the symmetric group performed as the monkey in Experiment 1; subjects from
the other group showed a sudden insightful solution of the problem. The different
performances in the same problem situation can be explained in terms of the
behavioral history provided to each group of subjects.
PMID- 27509892
TI - The ConNECT Framework: a model for advancing behavioral medicine science and
practice to foster health equity.
AB - Health disparities persist despite ongoing efforts. Given the United States'
rapidly changing demography and socio-cultural diversity, a paradigm shift in
behavioral medicine is needed to advance research and interventions focused on
health equity. This paper introduces the ConNECT Framework as a model to link the
sciences of behavioral medicine and health equity with the goal of achieving
equitable health and outcomes in the twenty-first century. We first evaluate the
state of health equity efforts in behavioral medicine science and identify key
opportunities to advance the field. We then discuss and present actionable
recommendations related to ConNECT's five broad and synergistic principles: (1)
Integrating Context; (2) Fostering a Norm of Inclusion; (3) Ensuring Equitable
Diffusion of Innovations; (4) Harnessing Communication Technology; and (5)
Prioritizing Specialized Training. The framework holds significant promise for
furthering health equity and ushering in a new and refreshing era of behavioral
medicine science and practice.
PMID- 27509893
TI - High-Performance Carbon Aerogel Air Cathodes for Microbial Fuel Cells.
AB - Microbial fuel cells (MFCs) can generate electricity from the oxidation of
organic substrates using anodic exoelectrogenic bacteria and have great potential
for harvesting electric energy from wastewater. Improving oxygen reduction
reaction (ORR) performance at a neutral pH is needed for efficient energy
production. Here we show a nitrogen doped (~4 wt%) ionothermal carbon aerogel
(NDC) with a high surface area, large pore volume, and hierarchical porosity,
with good electrocatalytic properties for ORR in MFCs. The MFCs using NDC air
cathodes achieved a high maximum power density of 2300 mW m-2 , which was 1.7
times higher than the most commonly used Pt/C air cathodes and also higher than
most state-of-the-art ORR catalyst air cathodes. Rotating disk electrode
measurements verified the superior electrocatalytic activity of NDC with an
efficient four-electron transfer pathway (n=3.9). These findings highlight NDC as
a better-performing and cost-efficient catalyst compared with Pt/C, making it
highly viable for MFC applications.
PMID- 27509894
TI - Sex-based differential regulation of bacterial-induced bone resorption.
AB - BACKGROUND AND OBJECTIVE: Periodontal disease pathogenesis is comprised of the
complex inflammatory immune response to oral bacterial dysbiosis. Like other
inflammatory diseases, there is sexual dimorphism evident in periodontal
diseases. During periodontitis, inflammatory chemokines direct neutrophils to
migrate to the site of infection to neutralize the pathogen. Interestingly, these
same chemokines are also involved in regulating pathogen-induced osteoclast
formation. Previous reports show differences in bone turnover and lymphocyte
recruitment between sexes. We hypothesize that chemokine expression is
differentially regulated by sex and thus results in differential osteoclast
formation. MATERIAL AND METHODS: Male and female mice were utilized to isolate
neutrophils based on expression of Ly6G-specific, as well as defined osteoclast
progenitors. Cells were stimulated with lipopolysaccharide (LPS; 100 ng/mL) then
analyzed for neutrophil infiltration and gene expression. Defined osteoclast
progenitors were primed: macrophage-colony stimulating factor (25 ng/mL),
receptor activator of NF-kappaB ligand (50 ng/mL), then stimulated with LPS.
Osteoclasts were enumerated via TRAP stain and mRNA isolated for gene expression
analysis via quantitative polymerase chain reaction. RESULTS: In response to LPS,
male neutrophils in vitro respond with increased chemokine expression and
significantly more osteoclast formed in response to LPS compared to females.
CONCLUSIONS: Findings support observations in humans regarding a sexual
dimorphism in oral bacterial infections of alveolar bone loss. Males have a
strong inflammatory response to bacterial infection, resulting in increased
inflammatory microenvironment, reduced pathogenic bacteria clearance and
increased osteoclast-driven bone loss in response to differential expression of
key chemokines.
PMID- 27509895
TI - Synthetic antimicrobial and LPS-neutralising peptides suppress inflammatory and
immune responses in skin cells and promote keratinocyte migration.
AB - The stagnation in the development of new antibiotics and the concomitant high
increase of resistant bacteria emphasize the urgent need for new therapeutic
options. Antimicrobial peptides are promising agents for the treatment of
bacterial infections and recent studies indicate that Pep19-2.5, a synthetic anti
lipopolysaccharide (LPS) peptide (SALP), efficiently neutralises pathogenicity
factors of Gram-negative (LPS) and Gram-positive (lipoprotein/-peptide, LP)
bacteria and protects against sepsis. Here, we investigated the potential of
Pep19-2.5 and the structurally related compound Pep19-4LF for their therapeutic
application in bacterial skin infections. SALPs inhibited LP-induced
phosphorylation of NF-kappaB p65 and p38 MAPK and reduced cytokine release and
gene expression in primary human keratinocytes and dermal fibroblasts. In LPS
stimulated human monocyte-derived dendritic cells and Langerhans-like cells, the
peptides blocked IL-6 secretion, downregulated expression of maturation markers
and inhibited dendritic cell migration. Both SALPs showed a low cytotoxicity in
all investigated cell types. Furthermore, SALPs markedly promoted cell migration
via EGFR transactivation and ERK1/2 phosphorylation and accelerated artificial
wound closure in keratinocytes. Peptide-induced keratinocyte migration was
mediated by purinergic receptors and metalloproteases. In contrast, SALPs did not
affect proliferation of keratinocytes. Conclusively, our data suggest a novel
therapeutic target for the treatment of patients with acute and chronic skin
infections.
PMID- 27509896
TI - The eardrum bridge of traumatic tympanic membrane perforation.
PMID- 27509897
TI - Prognostic significance of extracapsular spread in isolated neck recurrences in
head and neck squamous cell carcinoma patients.
AB - Few studies have analyzed the appearance of extracapsular spread (ECS) in salvage
neck dissections carried out after regional recurrence of the disease. The aim of
our study was to evaluate the frequency of ECS in patients with an isolated
regional recurrence treated with a salvage neck dissection, and to assess the
influence of ECS on prognosis. We conducted a retrospective study of 123 patients
treated with a salvage neck dissection. Eighty-two patients (66.7 %) had nodes
with ECS. Five-year salvage-specific survival for patients without ECS was 77.2
%, whereas for patients with ECS it was 32.0 % (P = 0.0001). According to the
results of a multivariate analysis, the presence of ECS in the salvage neck
dissection was the only variable significantly related to the salvage-specific
survival. Sixty-six percent of the patients with nodes with ECS had adjuvant
treatment with radiotherapy or chemoradiotherapy. Five-year salvage-specific
survival for patients with ECS who had not received adjuvant treatment (n = 26)
was 15.2 %, whereas for patients treated with adjuvant radiotherapy (n = 39) or
chemotherapy (n = 17), 5-year salvage-specific survival was 36.4 and 47.1 %,
respectively. Patients with ECS could benefit from adjuvant treatment with
radiotherapy or chemoradiotherapy.
PMID- 27509898
TI - Articulation Artifacts During Overt Language Production in Event-Related Brain
Potentials: Description and Correction.
AB - Overt articulation produces strong artifacts in the electroencephalogram and in
event-related potentials (ERPs), posing a serious problem for investigating
language production with these variables. Here we describe the properties of
articulation-related artifacts and propose a novel correction procedure.
Experiment 1 co-recorded ERPs and trajectories of the articulators with an
electromagnetic articulograph from a single participant. The generalization of
the findings from the single participant to standard picture naming was
investigated in Experiment 2. Both experiments provided evidence that
articulation-induced artifacts may start up to 300 ms or more prior to voice
onset or voice key onset-depending on the specific measure; they are highly
similar in topography across many different phoneme patterns and differ mainly in
their time course and amplitude. ERPs were separated from articulation-related
artifacts with residue iteration decomposition (RIDE). After obtaining the
artifact-free ERPs, their correlations with the articulatory trajectories dropped
near to zero. Artifact removal with independent component analysis was less
successful; while correlations with the articulatory movements remained
substantial, early components prior to voice onset were attenuated in
reconstructed ERPs. These findings offer new insights into the nature of
articulation artifacts; together with RIDE as method for artifact removal the
present report offers a fresh perspective for ERP studies requiring overt
articulation.
PMID- 27509899
TI - Combined DTI-fMRI Analysis for a Quantitative Assessment of Connections Between
WM Bundles and Their Peripheral Cortical Fields in Verbal Fluency.
AB - Diffusion tensor imaging (DTI) tractography and functional magnetic resonance
imaging (fMRI) are powerful techniques to elucidate the anatomical and functional
aspects of brain connectivity. However, integrating these approaches to describe
the precise link between structure and function within specific brain circuits
remains challenging. In this study, a novel DTI-fMRI integration method is
proposed, to provide the topographical characterization and the volumetric
assessment of the functional and anatomical connections within the language
circuit. In a group of 21 healthy elderly subjects (mean age 68.5 +/- 5.8 years),
the volume of connection between the cortical activity elicited by a verbal
fluency task and the cortico-cortical fiber tracts associated with this function
are mapped and quantified. An application of the method to a case study in neuro
rehabilitation context is also presented. Integrating structural and functional
data within the same framework, this approach provides an overall view of white
and gray matter when studying specific brain circuits.
PMID- 27509900
TI - The Importance of Aging in Gray Matter Changes Within Tinnitus Patients Shown in
Cortical Thickness, Surface Area and Volume.
AB - Aging and sensorineural hearing loss are known to be involved in the development
of chronic tinnitus. This study explores the structural changes of gray matter
using surface base methods and focuses more specifically on changes in cortical
thickness in 127 tinnitus patients. The linear relationships between cortical
thickness and behavioral measures including aging, tinnitus loudness, tinnitus
duration, tinnitus distress, and hearing loss were analyzed. Three dimensional T1
weighted MR images were acquired and cortical gray matter volumes were segmented
using FreeSurfer on Talairach space. The results showed that cortical thickness
and volume are negatively correlated to age in widespread regions of frontal
cortices, and positively to bilateral entorhinal cortex and left rostral anterior
cingulate cortex. The cortical thickness changes related to hearing loss overlap
with those related to normal aging. The gray matter volumes of bilateral
amygdalae, hippocampi, nuclei accumbens, and thalami are all significantly
negatively correlated to age. Tinnitus-related distress level and subjective
loudness were negatively correlated only to the thalamic volume. The results
suggest that the primary factor of long-term structural changes in chronic
tinnitus patients is age and age related hearing loss, rather than hearing loss
per se. Tinnitus related factors such as subjective tinnitus loudness, tinnitus
duration, and the level of chronic tinnitus related distress were not correlated
to important morphometric changes in this study.
PMID- 27509901
TI - Diverse Reactivity of an Electrophilic Phosphasilene towards Anionic
Nucleophiles: Substitution or Metal-Amino Exchange.
AB - The reaction of MesLi (Mes=2,4,6-trimethylphenyl) with the electrophilic
phosphasilene R2 (NMe2 )Si-RSi=PNMe2 (2, R=Tip=2,4,6-triisopropylphenyl) cleanly
affords R2 (NMe2 )Si-RSi=PMes and thus provides the first example of a
substitution reaction at an unperturbed Si=P bond. In toluene, the reaction of 2
with lithium disilenide, R2 Si=Si(R)Li (1), apparently proceeds via an initial
nucleophilic substitution step as well (as suggested by DFT calculations), but
affords a saturated bicyclo[1.1.0]butane analogue as the final product, which was
further characterized as its Fe(CO)4 complex. In contrast, in 1,2-dimethoxyethane
the reaction of 1 with 2 results in an unprecedented metal-amino exchange
reaction.
PMID- 27509902
TI - Congenital Zika syndrome with arthrogryposis: retrospective case series study.
AB - OBJECTIVE: To describe the clinical, radiological, and electromyographic features
in a series of children with joint contractures (arthrogryposis) associated with
congenital infection presumably caused by Zika virus. DESIGN: Retrospective case
series study. SETTING: Association for Assistance of Disabled Children,
Pernambuco state, Brazil. PARTICIPANTS: Seven children with arthrogryposis and a
diagnosis of congenital infection presumably caused by Zika virus during the
Brazilian microcephaly epidemic. MAIN OUTCOME MEASURES: Main clinical,
radiological, and electromyographic findings, and likely correlation between
clinical and primary neurological abnormalities. RESULTS: The brain images of all
seven children were characteristic of congenital infection and arthrogryposis.
Two children tested positive for IgM to Zika virus in the cerebrospinal fluid.
Arthrogryposis was present in the arms and legs of six children (86%) and the
legs of one child (14%). Hip radiographs showed bilateral dislocation in seven
children, subluxation of the knee associated with genu valgus in three children
(43%), which was bilateral in two (29%). All the children underwent high
definition ultrasonography of the joints, and there was no evidence of
abnormalities. Moderate signs of remodeling of the motor units and a reduced
recruitment pattern were found on needle electromyography (monopolar). Five of
the children underwent brain computed tomography (CT) and magnetic resonance
imaging (MRI) and the remaining two CT only. All presented malformations of
cortical development, calcifications predominantly in the cortex and subcortical
white matter (especially in the junction between the cortex and white matter),
reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and
cerebellum. MRI of the spine in four children showed apparent thinning of the
cord and reduced ventral roots. CONCLUSIONS: Congenital Zika syndrome should be
added to the differential diagnosis of congenital infections and arthrogryposis.
The arthrogryposis was unrelated to the abnormalities of the joints themselves,
but was possibly of neurogenic origin, with chronic involvement of central and
peripheral motor neurones leading to deformities as a result of fixed postures in
utero. Based on the neurophysiological observations, we suggest two possible
mechanisms: tropism of neurones, with involvement of peripheral and central motor
neurones, or a relation with vascular disorders.
PMID- 27509903
TI - What Value Can Qualitative Research Add to Quantitative Research Design? An
Example From an Adolescent Idiopathic Scoliosis Trial Feasibility Study.
AB - Using an example of qualitative research embedded in a non-surgical feasibility
trial, we explore the benefits of including qualitative research in trial design
and reflect on epistemological challenges. We interviewed 18 trial participants
and used methods of Interpretive Phenomenological Analysis. Our findings
demonstrate that qualitative research can make a valuable contribution by
allowing trial stakeholders to see things from alternative perspectives.
Specifically, it can help to make specific recommendations for improved trial
design, generate questions which contextualize findings, and also explore disease
experience beyond the trial. To make the most out of qualitative research
embedded in quantitative design it would be useful to (a) agree specific
qualitative study aims that underpin research design, (b) understand the impact
of differences in epistemological truth claims, (c) provide clear thematic
interpretations for trial researchers to utilize, and (d) include qualitative
findings that explore experience beyond the trial setting within the impact plan.
PMID- 27509904
TI - The nucleolytic resolution of recombination intermediates in yeast mitotic cells.
AB - In mitotic cells, the repair of double-strand breaks by homologous recombination
(HR) is important for genome integrity. HR requires the orchestration of a subset
of pathways for timely removal of joint-molecule intermediates that would
otherwise prevent segregation of chromosomes in mitosis. The use of nucleases to
resolve recombination intermediates is important for chromosome segregation, but
is hazardous because crossovers can result in loss of heterozygosity or
chromosome rearrangements. Unregulated use of the nucleases involved in the
resolution of recombination intermediates could also be a risk during
replication. The yeast models (Saccharomyces cerevisae and Schizosaccharomyces
pombe) have proven effective in determining the major nucleases involved in the
processing of such intermediates: Mus81-Mms4 and Yen1. Mus81-Mms4 and Yen1 are
regulated by the cell cycle in a gradual activation during G2/M to keep the
crossing-over risk low while ensuring proper removal of HJ intermediates.
PMID- 27509905
TI - NHS trust may shut emergency department at night because of staffing "crisis".
PMID- 27509906
TI - RUNX2 mutation impairs bone remodelling of dental follicle cells and periodontal
ligament cells in patients with cleidocranial dysplasia.
AB - RUNX2 is an important osteo-specific factor with crucial functions in bone
formation and remodelling as well as resorption of teeth. Heterozygous mutation
of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with
extensive skeletal dysplasia and abnormality of tooth growth. In our study,
dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) were
isolated, cultured and identified from one patient with CCD and compared with
normal controls. This CCD patient was confirmed to have a heterozygous frameshift
mutation of RUNX2 (c.514delT, p.Ser172fs) in the previous study. The results
showed that the proliferation abilities of DFCs and PDLCs were both disturbed by
the RUNX2 mutation in the CCD patient compared with the normal control. A co
culture system of these cells with human peripheral blood mononuclear cells was
then used to investigate the effect of RUNX2 mutation on osteoclastogenesis. We
found that the RUNX2 mutation in CCD reduced the expression of osteoclast-related
genes, such as RUNX2, CTR, CTSK, RANKL and OPG The ability of osteoclastogenesis
in DFCs and PDLCs detected by tartrate-resistant acid phosphatase staining in the
co-culture system was also reduced by the RUNX2 mutation compared with the normal
control. These outcomes indicate that the RUNX2 mutation disturbs the modulatory
effects of DFCs and PDLCs on the differentiation of osteoclasts and osteoblasts,
thereby interfering with bone remodelling. These effects may contribute in part
to the pathological manifestations of retention of primary teeth and delayed
eruption of permanent teeth in patients with CCD.
PMID- 27509907
TI - Hair Cortisol Concentrations in Adolescent Girls with Anorexia Nervosa are Lower
Compared to Healthy and Psychiatric Controls.
AB - OBJECTIVE: In anorexia nervosa (AN) hypercortisolism has been described using
urine, plasma and saliva samples as short-term markers for the hypothalamic
pituitary-adrenal (HPA)-axis. Here, for the first time, we analyse hair cortisol
concentration (HCC) as a marker for long-term integrated cortisol secretion in
female patients with AN compared to female healthy controls (HC) and female
psychiatric controls (PC). METHODS: HCC was assessed in 22 female adolescent
psychiatric inpatients with AN compared to 20 female HC and to 117 female PC of
the same age range. For further analyses we examined the associations of age and
body mass index (BMI) with HCC. RESULTS: Log HCC was lower in AN-patients
compared to HC (p = 0.030). BMI-standard deviation scores (SDS) but not age
correlated with log HCC (BMI-SDS: r = 0.19, bias corrected accelerated 95%
confidence interval: [.04, .34], p = 0.015; age: r = 0.10, bias corrected
accelerated 95% confidence interval: [-.07, .25], p = 0.213) when combining AN,
HC and PC samples. DISCUSSION: We find lower HCC in AN, compared to HC and PC,
respectively. Based on the relationship between HCC and BMI-SDS across AN, HC and
PC, we argue that HCC might not capture endocrine alterations because of AN
pathology-related processes but rather shows consistent relationships with BMI,
which extent even to the very low range of BMI values, as present in AN patients.
Alternatively, incorporation of cortisol into the hair follicle might have been
compromised because of trophic hair follicle disturbances that had been reported
in AN patients, previously. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating
Disorders Association.
PMID- 27509908
TI - Evidence That a Subset of Aneurysms Less Than 7 mm Warrant Treatment.
PMID- 27509909
TI - Consistency of Hemoglobin A1c Testing and Cardiovascular Outcomes in Medicare
Patients With Diabetes.
AB - BACKGROUND: Annual hemoglobin A1c testing is recommended for patients with
diabetes mellitus. However, it is unknown how consistently patients with diabetes
mellitus receive hemoglobin A1c testing over time, or whether testing consistency
is associated with adverse cardiovascular outcomes. METHODS AND RESULTS: We
identified 1 574 415 Medicare patients (2002-2012) with diabetes mellitus over
the age of 65. We followed each patient for a minimum of 3 years to determine
their consistency in hemoglobin A1C testing, using 3 categories: low (testing in
0 or 1 of 3 years), medium (testing in 2 of 3 years), and high (testing in all 3
years). In unweighted and inverse propensity-weighted cohorts, we examined
associations between testing consistency and major adverse cardiovascular events,
defined as death, myocardial infarction, stroke, amputation, or the need for leg
revascularization. Overall, 70.2% of patients received high-consistency testing,
17.6% of patients received medium-consistency testing, and 12.2% of patients
received low-consistency testing. When compared to high-consistency testing, low
consistency testing was associated with a higher risk of adverse cardiovascular
events or death in unweighted analyses (hazard ratio [HR]=1.21; 95% CI, 1.20
1.23; P<0.001), inverse propensity-weighted analyses (HR=1.16; 95% CI, 1.15-1.17;
P<0.001), and weighted analyses limited to patients who had at least 4 physician
visits annually (HR=1.15; 95% CI, 1.15-1.16; P<0.001). Less-consistent testing
was associated with worse results for each cardiovascular outcome and in analyses
using all years as the exposure. CONCLUSIONS: Consistent annual hemoglobin A1c
testing is associated with fewer adverse cardiovascular outcomes in this
observational cohort of Medicare patients of diabetes mellitus.
PMID- 27509910
TI - For Immunoglobulin Light Chains, It's Time to Fly!
PMID- 27509911
TI - Spotting the Cheaters.
PMID- 27509912
TI - Erratum: Mitochondrial Hormesis links nutrient restriction to improved metabolism
in fat cell.
PMID- 27509913
TI - Endocrine disrupting chemicals as potential risk factor for estrogen-dependent
cancers.
AB - Civilization, industrialization, and urbanization create an environment where
humans are continuously exposed to endocrine disrupting chemicals (EDCs). Some of
breast cancers and endometrial cancer, which are the most common female malignant
neoplasms, are estrogen-dependent tumors. Prolonged exposure to estrogens or
substances with estrogenic properties may be a risk factor for their development.
This paper aimed to discuss the potential adverse effect of EDCs on human health,
including the role of EDCs in hormone-dependent carcinogenesis. A review of
literature regarding the sources of environmental exposure to EDCs and molecular
mechanisms of their action was performed. We analyzed the possible mechanisms of
how these substances alter the function of the endocrine system, resulting in
adverse health effects. Hundreds of substances with endocrine disrupting
potential have been identified in our environment. There is accumulating evidence
linking exposure to EDCs with the development of mammary and endometrial cancer.
By interacting with steroid receptors, EDCs can impact the cellular processes
potentially leading to carcinogenesis. There are also data showing the effect of
EDCs on immune dysfunction. During lifespan, people are usually exposed to a
mixture of various EDCs, which complicates the assessment of individual
substances or compounds implicated in cancer development. As the prevalence of
hormone-dependent tumors among women continues to increase, their successful
prevention is of human benefit. Institutions representing medicine, science,
industry, and governments should develop joint strategies to decrease exposure to
EDC, and thus to reduce the risk of hormonedependent tumors in women.
PMID- 27509914
TI - Lycorine protects cartilage through suppressing the expression of matrix
metalloprotenases in rat chondrocytes and in a mouse osteoarthritis model.
AB - Extracellular matrix (ECM) degrading enzymes, including matrix metalloproteinases
(MMPs), are critical for cartilage destruction in the progression of
osteoarthritis (OA). Thus, identifying novel drugs, which suppress the synthesis
of MMPs may facilitate the treatment of OA. The cytotoxicity of lycorine was
determined using a CCK8 assay. The effects of lycorine on IL-1beta-induced
upregulation of MMPs and activation of mitogen-activated protein kinase pathways
were detected by western blot analysis and reverse transcription-quantitative
polymerase chain reaction. Hematoxylin and eosin staining and Safranin O staining
were used to evaluate the effect of lycorine in a mouse anterior cruciate
ligament transection model. In the present study, it was demonstrated for the
first time, to the best of our knowledge, that lycorine (LY) suppressed
interleukin-1beta (IL-1beta)-induced synthesis of MMP-3 and MMP-13 in vitro.
Molecular analysis revealed that LY abrogated the phosphorylation of c-Jun N
terminal kinase (JNK) and the activation of the nuclear factor (NF)-kappaB
signaling pathway caused by IL-1beta stimulation. In addition, in vivo
experiments in a mouse anterior cruciate ligament transection model confirmed the
protective role of LY on cartilage. Taken together, the data obtained in the
present study demonstrated that LY suppressed the IL-1beta-induced expression of
MMP-3 and MMP-13 through inhibition of the JNK and NF-kappaB pathways, suggesting
that LY may be used as a potential drug for the treatment of OA.
PMID- 27509915
TI - Effect of Transition From a Unit-Based Team to External Transport Team for a
Pediatric Critical Care Unit.
AB - OBJECTIVE: Pediatric hospitals must consider staff, training, and direct costs
required to maintain a pediatric specialized transport team, balanced with
indirect potential benefits of marketing and referral volume. The effect of
transitioning a unit-based transport team to an external service on the pediatric
intensive care unit (PICU) is unknown, but information is needed as hospital
systems focus on population management. We examined the impact on PICU transports
after transition to an external transport vendor. METHODS: Single-center
retrospective review performed of PICU admissions, referrals, and transfers
during baseline, post-, and maintenance period with a total of 9-year follow-up.
Transfer volume was analyzed during pre-, post-, and maintenance phase with
descriptive statistics and statistical process control charts from 1999 to 2012.
RESULTS: Total PICU admissions increased with an annual growth rate of 3.7%, with
mean annual 626 admissions prior to implementation to the mean of 890 admissions
at the end of period, P < .001. The proportion of transport to total admissions
decreased from 27% to 21%, but mean annual transports were unchanged, 175 to 183,
P = .6, and mean referrals were similar, 186 to 203, P = .8. Seasonal changes in
transport volume remained as a predominant source of variability. Annual
transport refusals increased initially in the postimplementation phase, mean 11
versus 33, P < .03, but similar to baseline in the maintenance phase, mean
20/year, P = .07. Patient refusals were due to bed and staffing constraints, with
7% due to the lack of transport vendor availability. CONCLUSION: In a transition
to a regional transport service, PICU transport volume was maintained in the long
term follow-up and total PICU admissions increased. Further research on the
direct and indirect impact of transport regionalization is needed to determine
the optimal cost-benefit and quality of care as health-care systems focus on
population management.
PMID- 27509916
TI - Withdrawing and Withholding Life Support in Patients With Cancer in an ICU
Setting: A 5-Year Experience at a European Cancer Center.
AB - OBJECTIVE: This was an observational retrospective study aimed to examine the
frequency and associated factors of withdrawing or withholding life support
(WWLS) in the intensive care unit (ICU) of a comprehensive cancer center.
METHODS: Medical records of adult patients with cancer admitted to the ICU
between January 2010 and December 2014 were reviewed. Patients who died during
that period were classified into 2 groups: full life support and withdrawing and
withholding life support. The relative impact of demographic and clinical factors
was assessed using logistic regression. RESULTS: A total of 247 patients died in
our unit (mortality rate of 16.3%). Their median age was 62 (interquartile range
[IQR] 51-73) years, there were 142 (57.5%) male patients, and they had
predominantly solid malignancies (62.3%). The median Simplified Acute Physiology
Score II and Acute Physiology and Chronic Health Evaluation scores were 67 (IQR
54-80) and 29 (IQR 23-55), respectively. Ninety-six (38.9%) patients died after
WWLS with no statistically significant differences in decisions to limit therapy
during the study period. Patients with advanced age, solid malignancies,
nonneutropenic, and longer duration of mechanical ventilation were more likely to
die after WWLS. In multivariate analysis, presenting with neutropenia was
independently associated with a lower likelihood of dying after WWLS (odds ratio:
0.34, 95% confidence interval: 0.15-0.80). CONCLUSION: Limitation of therapy has
been a common practice in oncologic ICUs over recent years. Neutropenia is an
independent predictor of limitation of therapy.
PMID- 27509917
TI - Extracorporeal Support for Chronic Obstructive Pulmonary Disease: A Bright
Future.
AB - In the past the only option for the treatment of respiratory failure due to acute
exacerbation of chronic obstructive pulmonary disease (aeCOPD) was invasive
mechanical ventilation. In recent decades, the potential for extracorporeal
carbon dioxide (CO2) removal has been realized. We review the various types of
extracorporeal CO2 removal, outline the optimal use of these therapies for
aeCOPD, and make suggestions for future controlled trials. We also describe the
advantages and requirements for an ideal long-term ambulatory CO2 removal system
for palliation of COPD.
PMID- 27509918
TI - Measuring younger onset dementia: A comprehensive literature search of the
quantitative psychosocial research.
AB - BACKGROUND: Research is beginning to demonstrate the unique psychosocial effects
of young onset dementia. Theorising remains at an early stage and there has been
little discussion about measurement and methodological issues. Our aim was to
conduct a comprehensive literature search of the young onset dementia
psychosocial research, and to identify the domains of experience measured with
patients and caregivers. METHOD: We conducted a search of five electronic
databases (Medline, CINAHL, PsycINFO, Embase, the Cochrane Library) using
equivalent database controlled vocabulary terms. We supplemented this search by
using free text searches within electronic databases, searching reference
sections of salient papers, and using online search engines. We defined
psychosocial as referring to patient and caregiver psychological, behavioural,
and social functioning in the context of living with young onset dementia.
RESULTS: We identified 72 published articles, 49 quantitative and 23 qualitative.
The quantitative articles form the focus of the present review. We identified 10
domains of patient experience measured and 14 domains of caregiver experience.
The patient domains measured most often were behaviour, cognition, functioning,
and severity, and reflected a focus on symptoms and clinical features. Quality of
Life (QoL) was the patient domain measured least often. The caregiver domains
measured most often were mental health and burden, and reflected a focus on
psychological well-being and coping. CONCLUSION: The scope of measurement is
broader in caregivers than patients. QoL although under-researched may be a
useful domain to measure in future research. Risk factors, measurement and
methodological issues are discussed.
PMID- 27509919
TI - How do activating interventions fit the personal needs, characteristics and
preferences of people with dementia living in the community and their informal
caregivers?
AB - Psychosocial interventions aim to mitigate the serious consequences of dementia
for the daily life of people with dementia and their informal caregivers. To
deliver a person-centred approach, it is crucial to take needs, characteristics
and preferences of people with dementia and their informal caregivers into
account. However, these factors are generally not systematically checked in order
to determine which intervention will be most appropriate. Additionally, little is
known about which intervention suits which needs, characteristics and
preferences. Therefore, this study examined how three multiple-component,
activating dyadic interventions fitted needs, characteristics, and preferences of
both the people with dementia and their informal caregivers: the Pleasant Events
Program, the Exercise and Support Intervention for People with Dementia and Their
Caregivers, and Occupational Therapy. Semi-structured interviews were held with
participants in either one of the interventions, 34 dyads and 19 professionals.
The constant comparative method was used for the analysis. Five factors
influenced the dyad's 'fit': timing, need for activity, lifestyle, apart-or
together and meaning of (lost) activity. The factors 'timing' and a 'need for
activity' were conditional for these activating interventions. Dyads in an early
stage of dementia, who were aware of the effects on daily life, were open to a
change in routine, and had a need to maintain activities profited from these
interventions. Three distinctive factors were important for the fit of one of the
three interventions in particular: 'lifestyle', 'apart or together' and 'meaning
of (lost) activity'. The Pleasant Events Programme and the Exercise and Support
intervention properly addressed the need for activities that afforded daily
pastimes or structure. The Exercise and Support Intervention addressed the need
for physical activity and emphasized shared activity. Occupational Therapy
properly addressed the need for self-sufficiency, maintaining activities and
adjustment to physical limitations. These factors can contribute to a more person
centred application of the interventions.
PMID- 27509920
TI - Postural stability in the cognitively impaired elderly: A systematic review of
the literature.
AB - INTRODUCTION: The aim of this study was to review the literature and critically
analyse publications connecting cognitive impairment with postural stability.
METHODS: Four electronic databases were searched. The inclusion criteria
comprised the relation between the process of maintaining balance and cognitive
impairment. RESULTS: Of the 153 selected articles, 15 met the inclusion criteria.
In 83% of publications, cognitive status was determined with the use of the Mini
Mental State Examination. In eight publications, postural stability was examined
using force plates. Other methods used to test the balance were functional tests,
i.e. the Berg Balance Scale or the Balance Evaluation Systems Test. CONCLUSION:
As the choice of methodology varies significantly, it is difficult to attempt an
objective comparison between different studies. There is a clear need for the
normalisation of methods used to assess the degree of dementia and to assess
postural stability among this group of people.
PMID- 27509921
TI - Increased NEK2 in hepatocellular carcinoma promotes cancer progression and drug
resistance by promoting PP1/Akt and Wnt activation.
AB - NIMA-related expressed kinase 2 (NEK2) participates in the carcinogenesis and
progression of certain types of cancer, however, its expression and roles in the
development of hepatocellular carcinoma (HCC) remains unknown. Here, we found
that NEK2 expression was significantly upregulated in both human HCC tissues and
cell lines, and increased NEK2 expression in HCC was significantly correlated
with clinical progression of HCC in patients. Knockdown of NEK2 in HCC cells
inhibited HCC progression, as determined by the suppressed cell proliferation,
invasion and metastasis. Furthermore, knockdown of NEK2 inhibited drug resistance
of HCC cells, as shown by the promoted suppression of cell viability in 5
fluorouracil (5-FU)-treated HCC cells. Mechanistically, protein phosphatase 1
(PP1)/Akt and Wnt signaling activation are significantly inhibited by NEK2
knockdown, which is responsible for the HCC progression and involved in NEK2
induced cancer cell abnormal biological behavior. Thus, enhanced NEK2 expression
in HCC promotes HCC progression and drug resistance by promoting PP1/Akt and Wnt
pathway activation, which may represent a new therapeutic target for HCC.
PMID- 27509923
TI - Observation of a Reactive Rainbow in F + CH3D -> CH2D(v = 0) + HF(v = 3)?
AB - Rainbow structures in the scattering angular distribution play an important role
in deepening our understanding about the elastic and rotationally inelastic
collisions of atoms/molecules. Reported here is the discovery of a rainbow in a
chemical reaction. At Ec = 4.3 kcal mol(-1) one of the correlated product pairs
in the F + CH3D reaction, (vHF, vCH2D) = (3, 00), displays a distinct bulge in
angular distribution. We showed that the bulge originates predominantly from the
low-j states of the HF(v = 3) products. Heuristic considerations led us to
propose that such a bulge could be regarded as a signature for rainbow
scattering. The underlying mechanism for its occurrence in this nearly
thermoneutral product pair is ascribed to a delicate interplay of the attractive
and repulsive parts of interactions in the vicinity of the transition state. In a
sense, the situation bears striking similarity to the more familiar elastic
rainbow, thus coined "reactive rainbow".
PMID- 27509924
TI - 15d-PGJ2 Induces Apoptosis of MCF-7 and MDA-MB-231 Cells via Increased
Intracellular Calcium and Activation of Caspases, Independent of ERalpha and
ERbeta.
AB - Reports indicate that 15deoxydelta12,14prostaglandinJ2 (15dPGJ2) has anticancer
activities, but its mechanisms of action have yet to be fully elucidated. We
therefore investigated the effects of 15dPGJ2 on the human breast cancer cell
lines, MCF7 (estrogen receptor ERalpha+/ERbeta+) and MDAMB231 (ERalpha/ERbeta+).
Cellular proliferation and cytotoxicity were determined using the
3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide (MTT) and lactate
dehydrogenase (LDH) assays while apoptosis was determined by fluorescence
microscopy and flow cytometry using annexin Vpropidium iodide (PI) staining. ER
expression was determined by Western blotting. Intracellular calcium was stained
with Fluo4 AM while intracellular caspase activities were detected with
CaspaseFLICA(r) and measured by flow cytometry. We showed that 15dPGJ2 caused a
significant increase in apoptosis in MCF7 and MDAMB231 cells. ERalpha protein
expression was reduced in treated MCF7 cells but preincubation with the ERalpha
inhibitor' ICI 182 780' did not affect the percentage of apoptotic cells. The
expression of ERbeta was unchanged in both cell lines. In addition, 15dPGJ2
increased intracellular calcium (Ca2+) staining and caspase 8, 9 and3/7
activities. We therefore conclude that 15dPGJ2 induces caspasedependent apoptosis
that is associated with an influx of intracellular Ca2+ with no involvement of ER
signaling.
PMID- 27509922
TI - Investigation of the association between miR-181b, Bcl-2 and LRIG1 in oral
verrucous carcinoma.
AB - Abnormal expression of microRNAs (miRNAs) is involved in the development of and
anti-apoptotic effects in various types of human cancer. However, miRNA-mediated
regulation of oral verrucous carcinoma (OVC) remains to be elucidated. The
present study aimed to investigate the expression of miR-181b in OVC and oral
squamous cell carcinoma (OSCC). The expression levels of miR-181b were determined
using reverse transcription-quantitative polymerase chain reaction. The
expression levels of B-cell lymphoma 2 (Bcl-2) and leucine rich repeats and
immunoglobulin like domains 1 (LRIG1), were evaluated using immunohistochemical
staining. The correlation between Bcl-2 and LRIG1 expression was determined using
a Pearson correlation analysis. The expression levels of miR-181b and Bcl-2 in
OVC were significantly higher compared with normal mucosal tissue (NM); however,
lower compared with the OSCC. The key target of miR-181b was LRIG1 and it was
significantly lower in OVC tissues compared with NM tissue; however this was
higher when compared with OSCC tissue. The expression levels of Bcl-2 were
correlated with expression levels of LRIG1 in OVC tissues. Therefore, LRIG1 may
be associated with anti-apoptotic function in OVC tissues.
PMID- 27509925
TI - Tyrosine Kinase Inhibitors in Ph+ Chronic Myeloid Leukemia Therapy: a Review.
AB - Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem
cell disorder. Deregulated BCRABL fusion tyrosine kinase activity is the main
cause of CML disease pathogenesis, making BCRABL an ideal target for inhibition.
Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCRABL oncoprotein
activity, have completely transformed the prognosis of CML. Interruption of TKI
treatment leads to minimal residual disease reside (MRD), thought to reside in
TKIinsensitive leukaemia stem cells which remain a potential reservoir for
disease relapse. This highlights the need to develop new therapeutic strategies
for CML either as small molecule master TKIs or phytopharmaceuticals derived from
nature to achieve chronic molecular remission. This review outlines the past,
present and future therapeutic approaches for CML including coverage of relevant
mechanisms, whether ABL dependent or independent, and epigenetic factors
responsible for developing resistance against TKIs. Appearance of mutant clones
along the course of therapy either preexisting or induced due to therapy is still
a challenge for the clinician. A proposed invitro model of generating colony
forming units from CML stem cells derived from diagnostic samples seems to be
achievable in the era of high throughput technology which can take care of single
cell genomic profiling.
PMID- 27509926
TI - Breast Cancer in Pakistan a Critical Appraisal of the Situation Regarding Female
Health and Where the Nation Stands?
AB - Breast cancer (BC) is the most common malignancy of women worldwide. In the past
it was considered as disease of older middle aged women, but the incidence of BC
in young females is growing in recent years concordant with studies in Pakistan.
In this paper, we reviewed the mutant functions of tumor suppressor genes (BRCA1,
BRCA2, p53, ATM and PTEN), epigenetic transformation and involvement of estrogen
receptors in development of breast cancer. We further reviewed the current
situation of BC in Pakistan that depicts a higher incidence in young females.
According to SKMCH and RC data, age group 4549 years is more prone to BC with
high rate of incidence 45.42%. A few studies explored the high expression of ER,
PR and HER2/neu in Pakistani females. Moreover, presence of BRCA1 (c.1961dupA)
mutation in Pakistani shows concordance with data in different areas of world.
But we are unable to find an authentic study that can explore epigenetic based
transformation of breast tumors in Pakistan. This area of research needs more
attention to explore the complete picture of BC in Pakistan.
PMID- 27509927
TI - Pleiotropic Roles of Metalloproteinases in Hematological Malignancies: an Update.
AB - Controlled remodeling of the extracellular matrix (ECM) is essential for cell
growth, invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of
secreted, zincdependent endopeptidases capable of degradation of ECM components.
The expression and activity of MMPs in a variety of human cancers have been
intensively studied. They play important roles at different steps of malignant
tumor formation and have central significance in embryogenesis, tissue
remodeling, inflammation, angiogenesis and metastasis. However, increasing
evidence demonstrates that MMPs are involved earlier in tumorigenesis. Recent
studies also suggest that MMPs play complex roles in tumor progression. MMPs and
membrane type (MT)MMPs are potentially significant therapeutic targets in many
cancers, so that designing of specific MMP inhibitors would be helpful for
clinical trials. Here, we review the pleiotropic roles of the MMP system in
hematological malignancies invitro and invivo models.
PMID- 27509928
TI - Gastric Carcinoma: Recent Trends in Diagnostic Biomarkers and Molecular Targeted
Therapies.
AB - Gastric cancer is generally associated with poor survival rates and accounts for
a remarkable proportion of global cancer mortality. The prevalence of gastric
carcinoma varies in different regions of world and across teh various ethnic
groups. On the basis of pathological assessment, gastric cancer can be
categorized as intestinal and diffuse carcinomas. The etiology is diverse,
including chemical carcinogen exposure, and high salt intake Helicobacter pylori
also plays a vital role in the pathogenesis of certain gastric carcinomas. The
development of gastric cancer involves various alterations in mRNAs, genes
(GOLPH3, MTA2) and proteins (Coronins). miRNAs, Hsamir135b, MiR21, miR106b,
miR17, miR18a, MiR21, miR106b, miR17, miR18a and MiRNA375, miRNA1955p are the
latest diagnostic biomarkers which can facilitate the early diagnosis of gastric
carcinomas. Recent development in the treatment strategies for gastric carcinoma
include the introduction of monoclonal antibodies, TKI inhibitors, inhibitors of
PDGFR beta, VEGFR1, VEGFR2, AntiEGFR and antiHER2 agents which can be applied
along with conventional therapies.
PMID- 27509929
TI - F2 Gel Matrix a Novel Delivery System for Immune and Gene Vaccinations.
AB - Exploiting the immune system to abolish cancer growth via vaccination is a
promising strategy but that is limited by many clinical issues. For DNA vaccines,
viral vectors as a delivery system mediate a strong immune response due to their
protein structure, which could afflect the cellular uptake of the genetic vector
or even induce cytotoxic immune responses against transfected cells. Recently,
synthetic DNA delivery systems have been developed and recommended as much easier
and simple approaches for DNA delivery compared with viral vectors. These are
based on the attraction of the positively charged cationic transfection reagents
to negatively charged DNA molecules, which augments the cellular DNA uptake. In
fact, there are three major cellular barriers which hinder successful DNA
delivery systems: low uptake across the plasma membrane; inadequate release of
DNA molecules with limited stability; and lack of nuclear targeting. Recently, a
polysaccharide polymer produced by microalgae has been synthesized in a form of
polymeric fiber material polyNacetyl glucosamine (pGlcNAc). Due its unique
properties, the F2 gel matrix was suggested as an effective delivery system for
immune and gene vaccinations.
PMID- 27509930
TI - Tetra Primer ARMS PCR Optimization to Detect Single Nucleotide Polymorphisms of
the CYP2E1 Gene.
AB - Single nucleotide polymorphism (SNP) detection has been used extensively for
genetic association studies of diseases including cancer. For mass, yet accurate
and more economic SNP detection we have optimized tetra primer amplification
refractory mutation system polymerase chain reaction (ARMS PCR) to detect three
SNPs in the cytochrome P450 2E1 (CYP2E1) gene locus; i.e. rs3813865, rs2070672
and rs3813867. The optimization system strategies used were (1) designing inner
and outer primers; (2) determining of their optimum primer concentration ratios;
and (3) determining of the optimum PCR annealing temperature. The tetra primer
ARMS PCR result could be directly observed using agarose gel electrophoresis. The
method succesfully determined three SNPs in CYP2E1 locus, the results being
consistent with validation using DNA sequencing and restriction fragment length
polymorphisms (RFLP).
PMID- 27509931
TI - Morin, a Flavonoid from Moraceae, Inhibits Cancer Cell Adhesion to Endothelial
Cells and EMT by Downregulating VCAM1 and Ncadherin.
AB - Morin, a flavonoid found in figs and other Moraceae species, displays a variety
of biological actions, exerting antioxidant, antiinflammatory and
anticarcinogenic effects. Here, we investigated the anticancer activity of morin
focusing on antiadhesive influence. We performed experiments with MDAMB231 human
breast cancer cells. Morin inhibited TNFinduced cancer cell adhesion to human
umbilical vein endothelial cells (HUVECs) without showing any toxicity. It
further inhibited the expression of VCAM1 on MDAMB231 cells as well as HUVECs.
Morin also decreased the expression of Ncadherin on MDAMB231 cells. In addition,
there was apparent antimetastatic activity in vivo. In conclusion, this study
suggested that morin inhibits cancer cell adhesion to HUVECs by reducing VCAM1,
and EMT by targeting Ncadherin, and that it features antimetastatic activity in
vivo. Further investigation of possible antimetastatic activity of morin against
human breast cancer cells is warranted.
PMID- 27509932
TI - AntiTumor and Immunoregulatory Effects of Fermented Papaya Preparation (FPP:
SAIDOPS501).
AB - Various beneficial effects have been described for fermented papaya preparation
(FPP: SAIDOPS501) based on its antioxidative and antiinflammatory functions. The
present study was designed to determine the effects of FPP on carcinogenesis in
vivo, and immunomodulatory function in vitro. Mice were injected with RL male 1
cells subcutaneously or 3methylcholantherene (MCA) intravenously to induce cancer
and orally or intraperitoneally treated with FPP solution. Human peripheral blood
mononuclear cells (PBMC) were obtained from healthy volunteers and patients with
atopic dermatitis, treated with FPP, and subjected to measurement of cytokine
production and changes in Foxp3expressing regulatory T cell (Treg) stimulated
with phytohemagglutinin (PHA). Administration of FPP suppressed tumor size and
the incidence of malignancy. In vitro, treatment of PBMC with FPP induced IL1?,
TNFalpha and IFNgamma production. Moreover, FPP suppressed proliferation of
PHAstimulated Foxp3expressing Treg. These results suggest that FPP has
chemotherapeutic properties.
PMID- 27509933
TI - Evaluation of KRAS Gene Mutations in Metastatic Colorectal Cancer Patients in
Kermanshah Province.
AB - BACKGROUND: Worldwide, colorectal cancer (CRC) is reported to be the fourth most
common cancer in men and the third most common in women. KRAS is a protooncogene
located on the short arm of chromosome 12. The aim of this study was to evaluate
the KRAS oncogene and its relationship it with clinicopathologic features in 33
Kurdish patients. MATERIALS AND METHODS: Metastatic CRC between 2012 and 2016
that came to Imam Reza hospital, Kermanshah province, Iran, were analysed for
KRAS mutations using allele specific PCR primers and pyrosequencing. Correlations
between variables was analyzed in PASW SPSS and overall survival curves were
plotted in Graph Pad prism 5. RESULTS: The mean age for them at diagnosis was
51.5+/-12.6 years (range, 2276 years). Among the 33 patients that were sequenced,
12 samples in the KRAS gene had a nucleotide change, 11 in codon 12 and 1 in
codon 13.There was no significant relationship between the mutation and clinical
and pathological aspects of the disease. CONCLUSIONS: Knowledge of the KRAS
status can help in decisionmaking to treat metastatic colorectal cancer patients
more efficiently and increase survival. However, many Kurdish people due to
economic problems are not able to do this valuable genetic test. In addition, we
need more careful research of KRAS oncogene at the molecular level in young
populations with more patients.
PMID- 27509934
TI - Does the Presence of Primary Circulating Prostate Cells Imply the Presence of
Agressive Prostate Cancer with Early Biochemical Failure: a Comparison with the
Walz Nomogram.
AB - BACKGROUND: To determine the utility of primary circulating prostate cells (CPC)
for predicting early biochemical failure after radical prostatectomy for prostate
cancer and compare the results with the Walz nomogram. MATERIALS AND METHODS: A
single centre prospective study of men with prostate cancer treated with radical
prostatectomy was conducted between 2004 and 2014. Clinicalpathological details
were registered, along with total serum PSA presurgery, Gleason score,
extracapsular extension, positive surgical margins, infiltration of lymph nodes,
seminal vesicles and pathological stage. Primary circulating prostate cells were
obtained using differential gel centrifugation and detected using standard
immunocytochemistry with antiPSA. Biochemical failure was defined as a PSA
>0.2ng/ml, predictive values were calculated using the Walz nomagram and CPC
detection. RESULTS: A total of 285 men participated, of whom 103/285 (36.1%)
suffered biochemcial failure; 32/103 (31.1%) within two years of radical
prostatectomy. Men with higher Gleason scores, higher pathological stage,
infiltration of the surgical margin or prostate capsule and infiltration of
seminal vesicles were more likely to undergo biochemical failure. There was a
significant increase in the frequency of biochemical failure with increasing
number of CPCs detected (p<0.0004 Chi squared for trend) and increasing percent
prediction for the Walz nomogram (p<0.0001 Chi squared for trends). The positive
predictive value of primary CPC detection, even using a cutoff point of >= 4
cells/sample was very low. CONCLUSIONS: The detection of primary CPCs in men as a
prognostic factor pretreatment fails to identify those at high risk of
biochemical failure within two years of curative therapy. This is in keeping with
their biological significance, that the majority of them will be eliminated by
the primary therapy and thus have no influence on the subsequent clinical history
of the patient.
PMID- 27509935
TI - Quality of Life of Patients with Advanced Cervical Cancer before and after
Chemoradiotherapy.
AB - BACKGROUND: Cervical cancer is the most frequently diagnosed cancer among women
in India. Understanding quality of life (QOL) in women undergoing
chemoradiotherapy for cervical cancer will help in introducing interventions for
better care and outcomes in these women. This study assessed QOL before and after
chemo radiotherapy in cervical cancer patients. MATERIALS AND METHODS: This
followup study covered sixtyseven newly diagnosed women with advanced cervical
cancer (stages 2b to 4b). Structured questionnaires (the European Organization
for Research and Treatment of Cancer, EORTC QLQC30 and EORTC QLQCX24) were used
to assess the change in QOL after 6 months of treatment. RESULTS: The mean age of
women at the time of detection of cervical cancer was 52.3+/-11.29 years (Range
3075 years). Six months survival was 92.53%. The mean global health score of
cervical cancer patients after six months of treatment was 59.52, which was
significantly higher than the pretreatment score of 50.15 (p=0.00007). Physical,
cognitive and emotional functioning improved significantly (p<0.05) after
treatment. Fatigue, pain, insomnia and appetite loss improved but episodes of
diarrhea increased after treatment. The mean "symptoms score" using EORTC QLQCX24
post treatment was 20.0 which was significantly lower as compared to the pre
treatment score 30.0 (p<0.00001). Sexual enjoyment and sexual functioning
decreased significantly after treatment. CONCLUSIONS: QOL of newly diagnosed
cervical cancer patients improved significantly following chemoradio therapy.
Enhancement was also demonstrated on three of the five functional scales of EORTC
QLQC30. To further improve QOL, interventions focusing on social and
psychological support and physical rehabilitation may be needed.
PMID- 27509936
TI - Prevalence of Abnormal Cervical Cytology in HIVNegative Women Participating in a
Cervical Cancer Screening Program in Calmette Hospital, Cambodia.
AB - Prevalence of Abnormal Cervical Cytology in HIVNegative Women Participating in a
Cervical Cancer Screening Program in Calmette Hospital, Cambodia.
PMID- 27509937
TI - Spiritual Needs of Patients with Cancer Referred to Alinasab and Shahid Ghazi
Tabatabaie Hospitals of Tabriz, Iran.
AB - BACKGROUND: Patients' spiritual needs increase drastically after a diagnosis of
cancer because of its threatening nature. It is very important to recognize any
spiritual crisis. This study aimed to determine needs among Iranian patients with
cancer. MATERIALS AND METHODS: This crosssectional study was undertaken among 200
patients with cancer referred to Alinasab and Shahid Ghazi Tabatabaie hospitals
of Tabriz, Iran. The Spiritual Needs Scale was used for data collection. RESULTS:
The mean age of participants was 45.9+/-16.4 years. The majority expressed their
main spiritual wishes as "think to God", "trust to God", "see others happy", "try
for life beside the disease", "to be prayed for by others', and "need for
kindness and help others". Regarding the relationship between demographic
characteristics, factors related to disease and the total score of spiritual
needs, the results of chisquare tests showed a significant statistical
correlations with occupation (p=0.01) and number of children (p=0.03). Also the
results of Pearson correlation showed that there is a significant statistical
correlation between hospitalization frequency and patients' spiritual needs
(p<0.01, r=0.24). CONCLUSIONS: Determination of spiritual needs of patients with
cancer in this study can help health carers and especially nurses to design
appropriate spiritual care programs based on individual preferences.
PMID- 27509938
TI - Comparing Recurrence and Complications After Laparoscopy and Laparotomy Surgery
among Patients Suffering from Colorectal Cancer, Shiraz, Iran.
AB - BACKGROUND: The goal of this study was to compare the rate of recurrence and
occurrence of complications in colorectal cancer patients after two kinds of
laparoscopy and laparotomy. MATERIALS AND METHODS: A followup study was carried
out among 358 patients who suffered from colorectal cancer from 20122014. The
data were gathered from colorectal research center in Shiraz, Shahid Faghihi
hospital, and analyzed using the chisquare test, logistic regression, and
multinomial regression. RESULTS: The average age of these patients was 56.3+/
14.6, 55.0% being men. Moreover, 57.8% of them underwent laparoscopy surgery and
42.2% of the patients underwent laparotomysurgery and the conversion rate was
58.0% which ultimately was put under the category of laparotomy surgery. After
biennial median followup, differences in the occurrence of complications such as
bleeding (hemorrhage), fever, intestine blockage and wound infection in these two
kinds of surgery werestatistically significant (P<0.05). However, the rate of
recurrence and the patients' ultimate status (alive without disease, alive with
disease, and death) did not significantly differ between these two surgery
groups. CONCLUSIONS: Post operation complications were laparoscopy surgery were
less than those in laparotomy. However, the outcomes such as patients' ultimate
status and recurrence were similar between the two groups.
PMID- 27509939
TI - Quantitative Analyses of Esophageal Cancer Research in Pakistan.
AB - BACKGROUND: Healthcare research is a neglected discipline in Pakistan and
research related to esophageal cancer (ranks 9th in Pakistani males and 5th in
females) is no exception in this regard. Particularly, there are no data
available to delineate the overall status of esophageal cancer epidemiological
studies in Pakistan. This study describes the first ever effort to make a
systematic quantification, in an attempt to provide a roadmap to all stakeholders
for designing appropriate epidemiological, diagnostic and therapeutic strategies.
MATERIALS AND METHODS: International (PubMed, ISI Web of Knowledge) and local
(PakMedinet) scientific databases as well as Google search engine were searched
using specified keywords to extract relevant publication. Well defined inclusion
criteria were implemented to select publications for final analyses. All data
were recorded by at least 3 authors and consensus data were entered into and
analyzed for descriptive statistics (such as frequencies, percentages and annual
growth rates) using Microsoft Excel and SPSS software. RESULTS: A total of 79
publications fulfilled the inclusion criteria including 20 publications for which
full texts were not available. Of the 79 publications, 59 (74.6%) were
original/research publications, 5 (6.3%) were case reports, 4 (5.1%) were
research communications, 2 (2.5%) were review articles, 1 was (1.2%)
correspondence and 8 (10.1%) were un defined categories. Only 13 <20%) cities of
Pakistan contributed towards the 79 publications. On average, only 1.9 relevant
publications/year were published from 1976 (year of first publication) to the
present. Alarmingly, a decline in the annual growth at 4.1% was recorded in the
last six years. CONCLUSIONS: Esophageal cancer research is largely unfathomed in
Pakistan. Urgent/dramatic steps are required by all concerned to address this
common (and under reported) cancer of Pakistan.
PMID- 27509940
TI - Surveillance Evaluation of the National Cancer Registry in Sabah, Malaysia.
AB - BACKGROUND: Cancer is the fourth leading cause of death in Sabah Malaysia with a
reported agestandardized incidence rate was 104.9 per 100,000 in 2007. The
incidence rate depends on nonmandatory notification in the registry.
Underreporting will provide the false picture of cancer control program
effectiveness. The present study was to evaluate the performance of the cancer
registry system in terms of representativeness, data quality, simplicity,
acceptability and timeliness and provision of recommendations for improvement.
MATERIALS AND METHODS: The evaluation was conducted among key informants in the
National Cancer Registry (NCR) and reporting facilities from FebMay 2012 and was
based on US CDC guidelines. Representativeness was assessed by matching cancer
case in the Health Information System (HIS) and state pathology records with
those in NCR. Data quality was measured through case finding and reabstracting of
medical records by independent auditors. The reabstracting portion comprised 15
data items. Selfadministered questionnaires were used to assess simplicity and
acceptability. Timeliness was measured from date of diagnosis to date of
notification received and data dissemination. RESULTS: Of 4613 cancer cases
reported in HIS, 83.3% were matched with cancer registry. In the state pathology
centre, 99.8% was notified to registry. Duplication of notification was 3%. Data
completeness calculated for 104 samples was 63.4%. Registrars perceived
simplicity in coding diagnosis as moderate. Notification process was moderately
acceptable. Median duration of interval 1 was 5.7 months. CONCLUSIONS: The
performances of registry's attributes are fairly positive in terms of simplicity,
case reporting sensitivity, and predictive value positive. It is moderately
acceptable, data completeness and inflexible. The usefulness of registry is the
area of concern to achieve registry objectives. Timeliness of reporting is within
international standard, whereas timeliness to data dissemination was longer up to
4 years. Integration between existing HIS and national registration department
will improve data quality.
PMID- 27509941
TI - E1/E2 of Hepatitis C Virus Genotype4 and Apoptosis.
AB - Several studies have addressed the possible role of hepatitis C virus genotype4
(HCV GT4) in apoptosis. However, this still not fully understood. In the current
study a reconstructed clone of E1/E2 polyprotein region of the HCV GT4 was
transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes
was used to investigate its possible significance for apoptosis. Out of the 84
genes, only 35 showed significant differential expression, 12 genes being
upregulated and 23 downregulated. The highestup regulated genes were APAF1
(apoptotic peptidaseactivating factor 1), BID (BH3 interacting domain death
agonist) and BCL 10 (Bcell CLL/ lymphoma protein 10) with fold regulation of
33.2, 30.1 and 18.9, respectively. The most downregulated were FAS (TNF receptor
super family), TNFRSF10B (tumor necrosis factor receptor superfamily member 10b)
and FADD (FASassociated death domain) with fold regulation of 30.2, 27.7 and
14.9, respectively. These results suggest that the E1/E2 proteins may be involved
in HCVinduced pathogenesis by modulating apoptosis through the induction of the
intrinsic apoptosis pathway and disruption of the BCL2 gene family.
PMID- 27509942
TI - 35Year Research History of Cytotoxicity and Cancer: a Quantitative and
Qualitative Analysis.
AB - Cancer is the leading cause of morbidity and mortality worldwide, characterized
by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly
is the basic function of chemotherapeutic drugs. However, these agents can damage
normal dividing cells, leading to adverse effects in the body. In view of great
advances in cancer therapy, which are increasingly reported each year, we
quantitatively and qualitatively evaluated the papers published between 1981 and
December 2015, with a closer look at the highly cited papers (HCPs), for a better
understanding of literature related to cytotoxicity in cancer therapy. Online
documents in the Web of Science (WOS) database were analyzed based on the
publication year, the number of times they were cited, research area, source,
language, document type, countries, organizationenhanced and funding agencies. A
total of 3,473 publications relevant to the target key words were found in the
WOS database over 35 years and 86% of them (n=2,993) were published between
20002015. These papers had been cited 54,330 times without self citation from
1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most
frequently cited ones between 2005 and 2015. The topmost HCP was about generating
a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third
of the remaining HCPs had focused on drug discovery through improving
conventional therapeutic agents such as metformin and ginseng. Another 33% of the
HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM)
dendritic polymers, PTX/SPIOloaded PLGAs and cell derived NPs to increase drug
effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs
reported novel factors such as miR205, Nrf2 and p27 suggesting their interference
with development of cancer in targeted cancer therapy. In conclusion, analysis of
35year publications and HCPs on cytotoxicity in cancer in the present report
provides opportunities for a better understanding the extent of topics published
and may help future research in this area.
PMID- 27509943
TI - Prevalence and Associated Factors of Abnormal Cervical Cytology and HighRisk HPV
DNA among Bangkok Metropolitan Women.
AB - BACKGROUND: Many strategies are required for cervical cancer reduction e.g.
provision of education cautious sexual behavior, HPV vaccination, and early
detection of preinvasive cervical lesions and invasive cancer. Basic health data
for cervical cytology/ HPV DNA and associated factors are important to make an
appropriate policy to fight against cervical cancer. AIMS: To assess the
prevalence of abnormal cervical cytology and/or HPV DNA and associated factors,
including sexual behavior, among Bangkok Metropolitan women. MATERIALS AND
METHODS: Thai women, aged 25to65 years old, had lived in Bangkok for >=5 years
were invited into the study. Liquidbased cervical cytology and HPV DNA tests were
performed. Personal data were collected. MAIN OUTCOMES MEASURES: Rates of
abnormal cytology and/ or highrisk HPV (HRHPV) and factors associated with
abnormal test(s) were studied. RESULTS: Abnormal cytology and positive HRHPV were
found in 6.3% (279/4442 women) and 6.7% (295/4428), respectively. The most common
abnormal cytology was ASCUS (3.5%) while the most common HRHPV genotype was HPV
16 (1.4%) followed by HPV 52 (1.0%), HPV 58 (0.9%), and HPV 18 and HPV 51 at
equal frequency (0.7%). Both tests were abnormal in 1.6% (71/4428 women). Rates
of HRHPV detection were directly associated with severity of abnormal cytology:
5.4% among normal cytology and 13.0%, 30.8%, 40.0%, 39.5%, 56.3% and 100.0% among
ASCUS, ASCH, AGCNOS, LSIL, HSIL, and SCC, respectively. Some 5% of women who had
no HRHPV had abnormal cytology, in which 0.3% had >= HSIL. Factors associated
with abnormal cytology or HRHPV were: age <=40 years, education lower than (for
cytology) or higher than bachelor for HRHPV), history of sexual intercourse, and
sexual partners >=2. CONCLUSIONS: Rates for abnormal cytology and HRHPV detection
were 6.3% and 6.7% HRHPV detection was directly associated with severity of
abnormal cytology. Significant associated factors were age <=40 years, lower
education, history of sexual intercourse, and sexual partners >=2.
PMID- 27509944
TI - Incidence and Management of Toxicity Associated with LAsparaginase in the
Treatment of ALL and NK/TCell Lymphoma: an Observational Study.
AB - BACKGROUND: Lasparaginase (ASNase) is commonly used in the treatment of acute
lymphoblastic leukemia (ALL) and natural killer (NK)/Tcell lymphoma. This study
was designed to describe the incidence of toxicity associated with ASNase in
Asian adults. Secondary objectives were to investigate the management and impact
of toxicity on subsequent ASNase use, and to compare the actual management
against current recommendations. MATERIALS AND METHODS: In this retrospective,
multicenter, observational study, Asian patients >= 18 years old who received >=
1 dose of the native E. coli ASNase from 2008 to 2013 were included. Patients
were excluded if they did not receive ASNase. Endpoints of this study were
development of specific toxicities, whether ASNase was discontinued or
rechallenged, and developmentg of recurrent toxicity. All data analyses were
performed using SPSS version 20.0. RESULTS: A total of 56 patients were analyzed.
Mean (+/-SD) age was 36.2 (+/-15.2) years old, with 62.5% being males, 55.4% with
ALL and 28.6% with NK/Tcell lymphoma. Hypersensitivity (12.5%) was associated
with the highest incidence of toxicity (6 out of 7 patients had Grade 3 and 4
toxicity), followed by 10.7% for hepatic transaminitis, 3.6% for nonCNS
thrombosis and 1.8% each for hyperbilirubinemia and pancreatitis.
Hypersensitivity recurred in the 3 patients who were rechallenged with E. coli
ASNase. CONCLUSIONS: ASNase is associated with a wide range of toxicities, with
hypersensitivity being the most commonly observed among Asian adult patients.
PMID- 27509945
TI - Utilization of Sunitinib for Renal Cell Cancer: an Egyptian University hospital
experience.
AB - BACKGROUND: Metastatic renal cell carcinoma (mRCC) status as poor prognosis
improved with the introduction of tyrosinekinase inhibitors, especially
sunitinib. There is sparse data reporting from our region on use of sunitinib in
metastatic RCC. Thus the present study explores sunitinib usage at our institute.
MATERIALS AND METHODS: An unselected population of patients with metastatic RCC
receiving sunitinib was analyzed with respect to patient characteristics,
response, toxicity, and outcomes. RESULTS: Fortynine patients with a median age
of 50.5 years (range 2171 years) were included. Most were male (61.2%). Twentyone
(42.9%) had metastatic disease at presentation. Sunitinib was first line therapy
in 45. Conventional clear cell carcinoma was the most common pathology present
(39 patients; 79.59 %). The most common site of metastasis was the lung (75.5%).
Most patients (30) were started at a dose of 50 mg once a day for 4 weeks and
then 2 weeks rest. Clinical benefit rate was 73.5% (n= 36), and 22.5% (n=11)
demonstrated progressive disease at first imaging evaluation within the first 36
months. The following objective response performed for patients was 48.9% (n=24)
and progression at 24.5 % (n=12). The median followup was 16 months (range, 434
months), the overall estimated median PFS was 9 months and the estimated median
OS was 15 months. CONCLUSIONS: This study demonstrated sunitinib is tolerable and
effective in advanced/metastatic RCC Egyptian patients and indicates we should
further seek second and third lines to increase survival equivalence as reported
in the worldwide literature.
PMID- 27509946
TI - Prostate Cancer, High Cortisol Levels and Complex Hormonal Interaction.
AB - Prostate cancer (PCa) is one of the most common diseases in men. It is important
to assess prognostic factors and whether high cortisol levels and complex
hormonal interactions could be responsible for PCa development. We evaluated the
relationship between cortisol, leptin and estrogens in 141 men, 71 with PCa and
the remaining 70 constituting a low risk group (LRG). They were recruited for
this study from a total of 2906 middleaged men (ages 4570 years) who completed an
evaluation for prostatic diseases at the Urology Division, Hospital de Clinicas
"Jose de San Martin", University of Buenos Aires, in May 2009. In this cross
sectional study, cortisol, PSA, totaltestosterone, freetestosterone, bioavailable
testosterone, LH and estradiol were measured in serum. We observed increased
cortisol levels in PCa patients as compared to LRG cases (p=0.004,). Leptin and
estradiol levels were also higher in PCa patients (p=0.048; p<0.0001,
respectively). Logistic regression analysis indicated that serum cortisol (OR:
1.110 (95% CI 1.0161.213), p=0.022), estradiol (OR: 1.044 (95% CI 1.0081.081),
p=0.016) and leptin (OR: 1.248 (95% CI 1.0481.487), p=0.013) explained 27% of the
variance of dependent variables, even after adjusting for age, smoking, BMI and
waist circumference. We found increased cortisol levels in PCa patients as
compared to LRG, as well as an altered circulating hormonal profile.
PMID- 27509947
TI - Financial Burden of Cancer Drug Treatment in Lebanon.
AB - BACKGROUND: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs
free of charge for uninsured patients who account for more than half the total
caseload. Other categories of cancer care are subsidized under more stringent
eligibility criteria. MOPH's large database offers an excellent opportunity to
analyze the cost of cancer treatment in Lebanon. MATERIALS AND METHODS: Using
utilization and spending data accumulated at MOPH during 20082013, the cost to
the public budget of cancer drugs was assessed per case and per drug type.
RESULTS: The average annual cost of cancer drugs was 6,475$ per patient. Total
cancer drug costs were highest for breast cancer, followed by chronic myeloid
leukemia (CML), colorectal cancer, lung cancer, and NonHodgkin's lymphoma (NHL),
which together represented 74% of total MOPH cancer drug expenditure. The annual
average cancer drug cost per case was highest for CML ($31,037), followed by NHL
($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug
expenditure over six years. CONCLUSIONS: Sustained increase in cancer drug cost
threatens the sustainability of MOPH coverage, so crucial for socially vulnerable
citizens. To enhance the bargaining position with pharmaceutical firms for drug
cost containment in a small market like Lebanon, drug price comparisons with
neighboring countries which have already obtained lower prices may succeed in
lowering drug costs.
PMID- 27509948
TI - Pioneering Annual Colorectal Cancer Screening and Treatment Targeting Low Income
Communities in Malaysia (20102015).
AB - The aim of this study was to assess the rate of uptake of a customised annual
Colorectal Cancer Awareness, Screening and Treatment Project (CCASTP) using
faecal immunohistochemical test (FIT) kits in low income communities in Malaysia.
The immediate objectives were (1) to evaluate the level of adherence of CRC
screening among lowincome groups, (2) to assess the knowledge and awareness of
the screened population and (3) to assess the accuracy of FIT kits. A total of
1,581 FIT kits were distributed between years 2010 to 2015 to healthy
asymptomatic participants of the annual CCASTP organized by Empowered the Cancer
Advocacy Society of Malaysia. Data for sociodemographic characteristics, critical
health and lifestyle information of the registered subjects were collected.
Findings for use of the FIT kits were collected when they were returned for stool
analyses. Those testingd positive were invited to undergo a colonoscopy
examination. A total of 1,436 (90.8%) of the subjects retuned the FITkits,
showing high compliance. Among the 129 subjects with positive FIT results, 92
(71.3%) underwent colonoscopy. Six cases (6.5%) of CRC were found. Based on the
data collected, the level of awareness of stool examination and knowledge about
CRC was poor amongst the participants. Gender, age group, ethnicity and risk
factors (i.e. smoking, lack of exercise and low consumption of fresh fruits) were
associated with positive FITkit results. In conclusion, CRC screening can be
performed in the community with a single FITkit. Although CRC knowledge and
awareness is poor in lowincome communities, the average return rate of the FIT
kits and rate of colonoscopy examination were 91.2% and 70.3%, respectively.
PMID- 27509949
TI - Applicability of Radioguided Occult Lesion Localization for NonPalpable Benign
Breast Lesions, Comparison with Wire Localization, a Clinical Trial.
AB - BACKGROUND: This study was designed to compare radioguided versus routine wire
localization of non palpable nonmalignant breast lesions in terms of efficacy for
complete excision, ease of use, time saving, and cosmetic outcome. MATERIALS AND
METHODS: Patients with nonpalpable breast masses and nonmalignant core biopsy
results who were candidates for complete surgical lumpectomy were enrolled and
randomly assigned to radioguided or wire localization groups. Radiologic,
surgical, and pathologic data were collected and analyzed to determine the
difficulty and duration of each procedure, ease of use, accuracy, and cosmetic
outcomes. RESULTS: This prospective randomized study included 60 patients,
randomly divided into wire guided localization (WGL) or radioguided occult lesion
localization (ROLL) groups. The mean duration of localization under ultrasound
guidance was shorter in the ROLL group (14.4 min) than in the WGL group (16.5
min) (p<0.001). The ROLL method was significantly easier for radiologists
(p=0.0001). The mean duration of the surgical procedure was 22.6 min (+/-10.3
min) for ROLL and 23.6 min (+/- 9.6 min) for WGL (p=0.6), a nonsignificant
difference. Radiography of the surgical specimens showed 100% lesion excision
with clear margins, as proved by pathologic examination, with both techniques.
The surgical specimens were slightly heavier in the ROLL group, but the
difference was not significant (p=0.06). CONCLUSIONS: The ROLL technique provides
effective, fast, and simple localization and excision of nonpalpable nonmalignant
breast lesions.
PMID- 27509950
TI - High Risk Human Papilloma Virus Genotypes in Kurdistan Region in Patients with
Vaginal Discharge.
AB - BACKGROUND: The human papilloma virus (HPV) is considered as the major risk
factor for the development of cervical cancer. This virus is of different
genotypes and generally can be classified into high and low risk types.
OBJECTIVE: To determine the rate of high risk HPV genotypes in women with vaginal
discharge and lower abdominal pain in Kurdistan region, Iraq. MATERIALS AND
METHODS: Cervical swabs were taken from 104 women. DNA was extracted and the
polymerase chain reaction (PCR) technique was used to determine the presence of
high risk genotypes. RESULTS: It was found that 13/104 (12.5%) of the samples
were positive for high risk HPV genotypes. Amongst those who were positive, 4/13
(30.7%) were typed as genotype 16 and 7/13 (53.8%) showed mixed genotyping. On
the other hand, genotypes 53 and 56 were found in only one sample each.
CONCLUSIONS: High risk HPV genotypes are not uncommon and further community based
study is needed to determine the prevalence of HPV and its genotypes and plan for
prevention of infection.
PMID- 27509951
TI - Skin Cancer: ClinicoPathological Study of 204 Patients in Southern Governorates
of Yemen.
AB - BACKGROUND: Skin cancer is a group of heterogeneous malignancies, in general
classified into nonmelanoma skin cancer (NMSC) and melanoma skin cancer (MSC).
Incidences are high in many parts in the world with considerable geographical and
racial variation. In the Yemen, there has been scarce information about skin
cancer. The aim of this study was to evaluate the demographic characteristics and
histological trend of skin cancer in Southern Governorates of Yemen. MATERIALS
AND METHODS: This retrospective study covered 204 cases of skin cancer at the
Modern Histopathology Laboratory and Aden Cancer Registry and Research Center,
Faculty of Medicine and Health Sciences, University of Aden, for the period
20062013. Data were classified regarding different demographic and tumor related
variables and analyzed using CanReg4 for cancer registry and SPSS (version 21).
RESULTS: The commonest encountered skin cancer was NMSC (93.1%). Generally, skin
cancer appears slightly more frequently in females than males with a 1:1.06 male:
female ratio, with a mean age of 62.9 years. Slightly higher than onethird
(36.3%) were from Aden governorate. The head and neck proved to be the most
common site in both males and females (58%). Basal cell carcinoma (BCC) is the
most common histological type of skin cancer (50.5%). CONCLUSIONS: Skin cancer is
a common cancer in patients living in southern governorates of Yemen. The pattern
appears nearly similar to the international figures with a low incidence of MSC.
PMID- 27509952
TI - Expression of the p16 and Ki67 in Cervical Squamous Intraepithelial Lesions and
Cancer.
AB - PURPOSE: To evaluate the expression of p16 and Ki67 in cervical intraepithelial
neoplasia (CIN) and cancer. MATERIALS AND METHODS: We performed a
immunohistochemical study of p16 and Ki67 in 243 cervical tissues 53
nondysplastic lesions, 106 CIN1, 61 CIN2/3 and 23 squamous cell carcinomas. The
expression of p16 and Ki67 was interpreted independently by 2 researchers and the
sensitivity and specificity to detect clinically significant lesions (>= CIN2)
were determined. RESULTS: The overall agreement results of positive or negative
immunostaining of intrainter observer variability were 0.659 for p16 and 0.808
for Ki67. p16 expression was demonstrated in 91.3% of invasive carcinomas, 78.7%
of CIN2/3, 10.4% of CIN1 and 9.4% of nondysplasic lesions. The corresponding Ki67
expression was: 100% of all invasive carcinomas, 75.4% of CIN2/3, 22.6% of CIN1,
and 11.3% with nondysplasia. The expression was significantly different between
CIN2/3 vs CIN1 for both p16 and Ki67 (pvalues <0.001 both), and cancer vs CIN2/3
for Ki67 (pvalue 0.008). The differences were not significant between CIN1 vs
nondysplasia (pvalues 1.000 for p16 and 0.130 of Ki67), and cancer vs CIN2/3 for
p16 (p value 0.219). The sensitivity and specificity to detect > CIN2 were 84.5%
and 90.5% by p16 and 82.1% and 88.6% by Ki67. CONCLUSIONS: The rates for 16 and
Ki67 expression were directly associated with the severity of cervical lesions.
Significant differences in these markers expression may be useful in cases with
equivocal histologic features among cervical intraepithelial lesions, but not
between CIN1 and nondysplastic lesions. The two markers had high sensitivity and
specificity in determining >CIN2.
PMID- 27509953
TI - Prevalent Signs and Symptoms in Patients with Skin Cancer and Nursing Diagnoses.
AB - BACKGROUND: Skin cancer has a remarkable importance given the high incidence in
the population. In Brazil, it is estimated that there were 98,420 new cases of
nonmelanoma skin cancer among men and 83,710 new cases among women in 2014.
OBJECTIVES: To verify signs and symptoms present in patients with skin neoplasms
according to the literature and relate them to the nursing diagnoses of NANDA
International. MATERIALS AND METHODS: Integrative literature review carried out
from March to May 2015 in the databases: Cumulative Index to Nursing and Allied
Health Literature, SCOPUS, National Library of Medicine and Nattional Institutes
of Health, Latin American and Caribbean Sciences of Health and Web of Science.
The descriptors used were: 'Signs and Symptoms' and 'Skin Neoplasms'. Sixteen
articles were identified as the final sample. After review, the signs and
symptoms of skin cancer identified in the literature were related to the defining
characteristics present in NANDA International, with the aim to trace possible
nursing diagnoses. RESULTS: The most prevalent signs and symptoms were:
asymmetric and well circumscribed nodules with irregular borders; speckles with
modified color aspect; ulcerations; blisters; pain; itching; and bleeding. The
principal nursing diagnoses outlined were: risk for impaired skin integrity;
impaired skin integrity; acute pain; risk of shock; and impaired comfort.
CONCLUSIONS: The identification of signs and symptoms present in patients with
skin cancer and the relationships of these with the nursing diagnoses of NANDA
International provide a basis for qualified and systematized nursing care to this
clientele.
PMID- 27509954
TI - Methyl Donor Status Influences DNMT Expression and Global DNA Methylation in
Cervical Cancer Cells.
AB - BACKGROUND: Methyl donor status influences DNA stability and DNA methylation
although little is known about effects on DNA methyltransferases. The aim of this
study was to determine whether methyldonor status influences DNA
methyltransferase (Dnmt) gene expression in cervical cancer cells, and if so,
whether there are associated effects on global DNA methylation. MATERIALS AND
METHODS: The human cervical cancer cell line, C4 II, was grown in complete medium
and medium depleted of folate (FM+) and folate and methionine (FM). Growth rate,
intracellular folate, intracellular methionine and homocysteine in the
extracellular medium were measured to validate the cancer cell model of methyl
donor depletion. Dnmt expression was measured by qRT PCR using relative
quantification and global DNA methylation was measured using a flow cytometric
method. RESULTS: Intracellular folate and methionine concentrations were
significantly reduced after growth in depleted media. Growth rate was also
reduced in response to methyl donor depletion. Extracellular homocysteine was
raised compared with controls, indicating disturbance to the methyl cycle.
Combined folate and methionine depletion led to a significant downregulation of
Dnmt3a and Dnmt3b; this was associated with an 18% reduction in global DNA
methylation compared with controls. Effects of folate and methionine depletion on
Dnmt3a and 3b expression were reversed by transferring depleted cells to complete
medium. CONCLUSIONS: Methyl donor status can evidently influence expression of
Dnmts in cervical cancer cells, which is associated with DNA global
hypomethylation. Effects on Dnmt expression are reversible, suggesting reversible
modulating effects of dietary methyl donor intake on gene expression, which may
be relevant for cancer progression.
PMID- 27509955
TI - Bone Mineral Density and Breast Cancer Risk Factors among Premenopausal and
Postmenopausal Women A Systematic Review.
AB - BACKGROUND: Bone mineral density (BMD) is a lifetime marker of estrogen in a
woman's body and has been associated with increased breast cancer risk.
Nonetheless the actual association is still debatable. Furthermore, estrogen is
very crucial in maintaining human bone density and gradually decreases over age.
A systematic search was conducted to assess any association of BMD with breast
cancer risk factors among premenopausal and postmenopausal women. MATERIALS AND
METHODS: Review identification was performed through databases searching on
MEDLINE, CINAHL and SCOPUS and 19 qualified studies were elected. The keywords
used were "bone mineral density", "breast cancer", and "breast density". RESULTS:
A total of 19 articles showed variation with the majority of the studies focused
on postmenopausal and a few focused on premenopausal women. Overall there was no
concensus on effects. CONCLUSIONS: An enormous effort is being undertaken by
researchers to prove that BMD might be one of the significant risk factors for
breast cancer.
PMID- 27509956
TI - HealthCare Providers' and Parents' Perspectives on Complementary Alternative
Medicine in Children with Cancer in Indonesia.
AB - BACKGROUND: Complementary alternative medicine (CAM) use in children with cancer
is widespread. Health care providers (HCP) need to acknowledge and address this
need. This study explored and compared perspectives on CAM of HCP and parents of
young patients with cancer in Indonesia. MATERIALS AND METHODS: We conducted a
crosssectional study using semistructured questionnaires in HCP and parents of
childhood cancer patients at an Indonesian academic hospital. RESULTS: A total of
351 respondents participated: 175 HCP (response rate 80%) and 176 parents
(response rate 80%). Parents were more likely than HCP to think that chemotherapy
can cure cancer (80% compared to 69%, P=0.013). Nearly half of all parents (46%)
and HCP (45%) doubted whether CAM can cure cancer. Parents were more likely than
HCP to think that CAM can be helpful in childhood cancer treatment (54% compared
to 35%, P=0.003). The most recommended CAM by HCP was selfprayer (93%). Reasons
for recommending CAM were: hope for improvement of the child's condition (48%),
patient wants to stop treatment (42%). Most discouraged CAM by HCP was by
oldsmart people (70%), the reasons being: lack of evidence for usefulness (77%),
lack of CAM knowledge (75%). The proportion thinking that patients were unlikely
to raise the CAM topic if they perceived that doctors were skeptical was higher
in parents than in HCP (52% versus 1%) (P<0.001). Most HCP (71%) and parents
(77%) acknowledged that their knowledge about safety and efficacy of CAM was
inadequate (P=ns). The proportion that wanted to learn or read more about CAM was
higher among parents than HCP (48% compared to 31%, P=0.002). CONCLUSIONS: HCP
and parents have different perspectives on CAM use in children with cancer. HCP
should enhance their CAM knowledge and encourage open communication about CAM
with parents. If doctors' skepticism is perceived, parents are unlikely to raise
CAM as a topic.
PMID- 27509957
TI - Survival of Patients with Stomach Cancer and its Determinants in Kurdistan.
AB - BACKGROUND: Stomach cancer is the fourth most common cancer and the second
leading cause of death from cancer in the world. In Iran, this type of cancer has
high rates of incidence and mortality. This study aimed to assess the survival
rate of patients with stomach cancer and its determinants in Kurdistan, a
province with one of the highest incidence rates of stomach cancer in the
country. MATERIALS AND METHODS: We studied a total of 202 patients with stomach
cancer who were admitted to Tohid Hospital in Sanandaj from 2009 to 2013. Using
KaplanMeier nonparametric methods the survival rate of patients was calculated in
terms of different levels of age at diagnosis, gender, education, residential
area, occupation, underweight, and clinical variables including tumor histology,
site of tumor, disease stage, and type of treatment. In addition, we compared the
survival rates using the logrank test. Finally, Cox proportional hazards
regression was applied using Stata 12 and R 3.1.0 software. The significance
level was set at 0.05. RESULTS: The mean age at diagnosis was 64.7 +/- 12.0
years. The survival rate of patients with stomach cancer was 43.9% and 7% at the
first and the fifth year after diagnosis, respectively. The results of logrank
test showed significant relationships between survival and age at diagnosis,
education, disease stage, type of treatment, and degree of being underweight
(P<0.05). Moreover, according to the results of Cox proportional hazards
regression model, the variables of education, disease stage, and type of
treatment were associated with patient survival (P<0.05). CONCLUSIONS: The
survival rate of patients with stomach cancer is low and the prognosis is very
poor. Given the poor prognosis of the patients, it is critical to find ways for
early diagnosis and facilitating timely access to effective treatment methods.
PMID- 27509958
TI - EGFR Mutation Genotype Impact on the Efficacy of Pemetrexed in Patients with
Nonsquamous Nonsmall Cell Lung Cancer.
AB - BACKGROUND: Pemetrexed monotherapy has come to be recognized as one of the
standard secondline therapies for advanced nonsquamous nonsmall cell lung cancer
(NSCLC). However, there have been no reports of studies that have evaluated the
efficacy of pemetrexed according to type of active EGFR mutation, i.e., an exon
19 deletion or an L858R point mutation. MATERIALS AND METHODS: The records of
nonsquamous NSCLC patients harboring an EGFR mutation who received pemetrexed
monotherapy as a second or later line of chemotherapy at Kitasato University
Hospital between March 2010 and October 2015 were retrospectively reviewed, and
the treatment outcomes were evaluated. RESULTS: The overall response rate and
progressionfree survival time (PFS) of the 53 patients with nonsquamous NSCLC
were 15.1% and 2.3 months, respectively. There were significant differences
between the disease control rate (37.5% vs. 76.2%) and PFS time (1.8 months vs.
3.3 months) of the exon 19 deletion group and the L858R point mutation group, and
a multivariate analysis identified type of EGFR mutation as well as performance
status (PS) as independent predictors of PFS. CONCLUSIONS: The clinical data
obtained in this study provided a valuable rationale for considering type of EGFR
mutation as well as non squamous histology as predictors of the efficacy of
pemetrexed monotherapy.
PMID- 27509959
TI - Type 2 Diabetes Mellitus as a Risk Factor for Female Breast Cancer in the
Population of Northern Pakistan.
AB - BACKGROUND: There has been much research work in the past to ascertain the
association between type 2 diabetes mellitus and breast cancer, but definitive
evidence has been scanty. The present study was carried out to determine the
association of type 2 diabetes mellitus with breast cancer in the female
population of Northern Pakistan. MATERIALS AND METHODS: This casecontrol study
was carried out in the Oncology Department of NORI Hospital. A total of 400
patients were included. Data were entered into PSPP 0.8.1. Twotailed significance
tests were used and a pvalue of 0.05 was considered significant. RESULTS: There
were a higher percentage of postmenopausal women in the diabetic breast cancer
patients' group as compared to the nondiabetic subset. The odds ratio for the
association between diabetes and risk of developing breast cancer was elevated
with statistical significance (OR = 2.96; 95 % CI =1.36.3; pvalue=0.004). The
results of our study showed that diabetes is associated with a risk of developing
breast cancer, especially in postmenopausal women (OR = 4.928; 95 % CI = 2.111.3;
pvalue=0.001). The association was particularly marked in obese subjects (OR =
31.49; 95 % CI = 1.8 536; p value=0.01), as compared to nonobese subjects (OR =
0.642; 95 % CI = 0.21.7). CONCLUSIONS: Diabetes is strongly associated with
obesity and it tends to increase the risk of breast Cancer, especially in
postmenopausal women. A highrisk subset for breast cancer comprised
postmenopausal, diabetic and overweight women.
PMID- 27509961
TI - Can We Rely on GLOBOCAN and GBD Cancer Estimates? Case Study of Lung Cancer
Incidence and Mortality Rates and Trends in Iran.
AB - BACKGROUND: Around half of input data in the global burden of disease cancer
collaboration (GBDCC) and GLOBOCAN projects come from low quality sources, mainly
from developing countries. This may lead to loss of precision in estimates. Our
question was: Are the absolute values and trends of the GBDCC and GLOBOCAN
estimates for lung cancer (LC) in Iran consistent with available statistics?.
MATERIALS AND METHODS: Incidence and mortality statistics were extracted from
national reports (N.IRs and N.MRs) and GBDCC (GBDincidence and mortality) and
GLOBOCAN databases for 19902013 where available. Trends were analyzed and
absolute values and annual percentage changes (APCs) were estimated and compared.
Incompleteness of case ascertainment at the Iranian national cancer registry and
Iranian national civil registration was assessed for better understanding.
RESULTS: Trends of N.IRs were significantly rising for males (APC: 19.4; 95% CI:
12.526.7) and females (23.2; 16.030.8). Trends of GBDincidence were stable for
males (0.2; 1.51.1) and females (1.0; 2.30.4). Absolute N.IRs were less than
GBDincidence steadily except for 2009. Trend of N.MRs was increasing up to 2004,
but stable thereafter. Trends of GBDmortality were also stable. Absolute N.MRs
were less than GBDmortality for years up to 2003 and more than GBDmortality since
2005. The estimates of GLOBOCAN were more than N.IRs and N.MRs. CONCLUSIONS: The
GBDCC and GLOBOCAN values for LC in Iran are underestimates. Generation of data
quality indices to present along with country specific estimates is highly
recommended.
PMID- 27509960
TI - Suitable Food Textures for Videofluoroscopic Studies of Swallowing in Esophageal
Cancer Cases to Prevent Aspiration Pneumonia.
AB - AIMS: To determine suitable food textures for videofluoroscopic study of
swallowing (VFSS), in order to predict and prevent subsequent aspiration
pneumonia in esophageal cancer patients with dysphagia after surgery. MATERIALS
AND METHODS: We evaluated 45 hospitalized esophageal cancer patients who
underwent surgery between January 2012 and December 2013. The control group
consisted of 43 patients treatmed from January 2010 until December 2011 and were
not examined by VFSS. Test foods, which were presented in order of increasing
thickness, included thin barium sulfate (Ba) liquid (3 or 10 ml), slightly
thickened Ba liquid (3 or 10 ml), a spoonful of Ba jelly, and a spoonful of Ba
puree. RESULTS: Patients could most safely swallow puree, followed by jelly. The
3mL samples of both the thin and thick liquids put patients at risk for
aspiration pneumonia, with incidence rates of 13% and 11%, respectively. While
64.4% of patients could swallow all test foods and liquids safely, 35.6% were at
risk for aspiration pneumonia when swallowing liquids. Even though >30% of
patients were at risk, only 1 (2.2%) in the VFSS group developed aspiration
pneumonia, which occurred at the time of admission. Following VFSS, no incidence
of aspiration pneumonia was observed. However, aspiration pneumonia occurred in 4
(9.3%) control patients during hospitalization. CONCLUSIONS: Postoperative
esophageal cancer patients were more likely to aspirate any kind of liquid than
solid foods, such as jellies. VFSS is very useful in determining suitable food
textures for postoperative esophageal cancer patients.
PMID- 27509962
TI - Clinical Outcomes of Intracranial Nonvestibular Schwannomas Treated with
LinacBased Stereotactic Radiosurgery and Radiotherapy.
AB - BACKGROUND: Intracranial nonvestibular schwannomas arising from various cranial
nerves excluding CN VIII are uncommon. Recently, stereotactic radiosurgery (SRS)
and fractionated stereotactic radiotherapy (SRT) have been widely reported as
effective treatment modalities for nonvestibular schwannomas. The purpose of this
study was to study the long term clinical outcome for nonvestibular schwannomas
treated with both XKnife and CyberKnife (CK) radiosurgery at one institution.
MATERIALS AND METHODS: From 2004 to 2013, fiftytwo nonvestibular schwannoma
patients were included in this study, 33 patients (63%) were treated with CK, and
19 (37%) were treated with XKnife. The majority of the tumors were jugular
foramen schwannomas (38%) and trigeminal schwannomas (27%). HSRT was given for 45
patients (86%), whereas CSRT was for 6 (12%) and SRS for 1 (2%). RESULTS: The
median pretreatment volume was 9.4 cm3 (range, 0.5752 cm3). With the median
follow up time of 36 months (range, 3135), the 3 and 5 year progression free
survival was 94 % and 88%, respectively. Tumor size was decreased in 13 (25%),
stable in 29 (56%), and increased in 10 (19%). Among the latter, 3 (30%) required
additional treatment because of neurologic deterioration. No patient was found to
develop any new cranial nerve deficit after SRS/SRT. CONCLUSIONS: These data
confirmed that SRS/ SRT provide high tumor control rates with low complications.
Large volume tumors and cystic expansion after radiation should be carefully
followed up with neurological examination and MRI, because it may frequently
cause neurological deterioration requiring further surgery.
PMID- 27509963
TI - Oxaliplatin, 5Fluorouracil and Leucovorin (FOLFOX4) as First Line Chemotherapy in
Elderly Patients with Advanced Gastric Cancer.
AB - BACKGROUND: Gastric cancer is considered the fourth most common cancer and second
most common cause of cancerrelated mortalities worldwide. Gastric cancer develops
more frequently among elderly. The oxaliplatin/5FU/leucovorin (FOLFOX) regimen
has shown a notable activity against gastric cancer. AIM: To evaluate the
responses and complications of FOLFOX4 regimen as first line chemotherapy in
elderly patients with advanced gastric cancer. MATERIALS AND METHODS: From
October 2014 to November 2015, a total of 21 patients with metastatic or local
AGC (advanced gastric cancer) were analyzed. All patients were administered a
FOLFOX4 regimen consisting of a 2h infusion of oxaliplatin 85 mg/m2 (day 1),
continuous infusion of 1000mg/ m2 5Fu in 24h., and leucovorin 200 mg/m2 in 2h
infusion as a firstline chemotherapy. RESULTS: A total of 18 patients were
assessable for efficacy and toxicity. One of 18 patients achieved a complete
response, and 12 had partial responses, giving an overall response rate of 72.6%.
Three (16%) patients demonstrated stable disease and 2 (12%) progression. The
median progression free survival was 7.3 months, and the median overall survival
was 11.9 months. One patient had grade 3 neuropathy. No other grade 3 or 4 NCICTC
were seen. CONCLUSIONS: The FOLFOX4 regimen used in our study was both active and
acceptable for AGC in elderly patients as neoadjuvant and main therapy.
PMID- 27509964
TI - Phytochemicals from Goniothalamus griffithii Induce Human Cancer Cell Apoptosis.
AB - Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii
include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study
were to investigate the cytotoxic activities of PCN and GTN and their influence
on molecular signaling for cell death in several human cancer cell lines compared
to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent
cytotoxicity against MCF7 > HeLa > HepG2 > NIH3T3 cells with IC50 values of 7.33,
14.8, 37.1 and 65.4 MUM, respectively, whereas PCN was cytotoxic only to HepG2
cells with IC50 values of ~80 MUM. Apoptotic cell death was confirmed by staining
the cells with annexin VFITC and propidium iodide (PI) employing flow cytometry.
Apoptosis was shown by externalization of phosphatidylserine in
goniothalamintreated MCF7 cells in a dose response manner. Positive PIstained
cells with the typical morphology of apoptotic cells were increased
dosedependently. Furthermore, reduction of mitochondrial transmembrane potential
was found in goniothalamintreated MCF7, HepG2 and HeLa cells. GTN treatment in
MCF7 increased caspase3, 8 and 9 activities while GTNinduced HeLa cells showed an
increase of both caspase3 and 9 activities. But an increased caspase8 activity
was demonstrated in GTN and PCNtreated MCF7 and HepG2 cells, respectively. Taken
together, GTN and PCNinduced human cancer cell apoptosis was through different
molecular mechanisms or signaling pathways, which might be due to different
machineries in different types of cancer cells, as evidenced by the
compoundmodulated caspase activities in both intrinsic and/or extrinsic pathways.
PMID- 27509965
TI - Induction of Human Hepatocellular Carcinoma HepG2 Cell Apoptosis by Naringin.
AB - Naringin, a bioflavonoid found in Citrus seeds, inhibits proliferation of cancer
cells. The objectives of this study were to investigate the mode and mechanism(s)
of hepatocellular carcinoma HepG2 cell death induced by naringin. The
cytotoxicity of naringin towards HepG2 cells proved dosedependent, measured by
MTT assay. Naringintreated HepG2 cells underwent apoptosis also in a
concentration related manner, determined by annexin Vfluorescein isothiocyanate
(FITC) and propidium iodide (PI) employing flow cytometry. Mitochondrial
transmembrane potential (MTP) measured using 3,3'dihexyloxacarbocyanine iodide
(DiOC6) and flow cytometer was reduced concentrationdependently, which indicated
influence on the mitochondrial signaling pathway. Caspase3, 8 and 9 activities
were enhanced as evidenced by colorimetric detection of paranitroaniline tagged
with a substrate for each caspase. Thus, the extrinsic and intrinsic pathways
were linked in human naringintreated HepG2 cell apoptosis. The expression levels
of proapoptotic Bax and Bak proteins were increased whereas that of the
antiapoptotic BclxL protein was decreased, confirming the involvement of the
mitochondrial pathway by immunoblotting. There was an increased expression of
truncated Bid (tBid), which indicated caspase8 proteolysis activity in Bid
cleavage as its substrate in the extrinsic pathway. In conclusion, naringin
induces human hepatocellular carcinoma HepG2 cell apoptosis via
mitochondriamediated activation of caspase9 and caspase8mediated proteolysis of
Bid. Naringin anticancer activity warrants further investigation for application
in medical treatment.
PMID- 27509966
TI - MDM2 Expression in Serous and Mucinous Epithelial Tumours of the Ovary.
AB - BACKGROUND: Different types of cancer exhibit abnormalities in cell cycle
regulators. The murine double minute2(MDM2) cell cycle regulator is a
protooncogene that negatively regulates the P53 tumour suppressor gene. Surface
epithelial tumours constitute approximately two thirds of ovarian neoplasms. Each
histologic type can be classified as benign, borderline and malignant. This study
aimed to examine immunohistochemical expression of the MDM2 protein in ovarian
serous and mucinous epithelial tumours (benign, borderline and malignant).
MATERIALS AND METHODS: This study included forty five ovarian tumours, subdivided
into fifteen cystadenomas (5 serous and 10 mucinous), fifteen borderline tumours
(11 serous and 4 mucinous) and fifteen cystadenocarcinomas (9 serous and 6
mucinous). Paraffin sections were stained with haematoxylin and eosin for
histopathologic study, and with mouse monoclonal antiMDM2 antibody for
immunohistochemistry. RESULTS: MDM2 positivity was detected in 28.9% of the
studied ovarian tumours. All benign tumours were negative and positivity was
significantly higher in malignant than borderline tumours (P value of chisquare
test =0.000). Significantly, all MDM2 positive mucinous tumours were malignant
with no positive mucinous borderline tumours. Malignant tumours showed positive
MDM2 expression in 83.3% of mucinous type and in 55.6% of serous type. Borderline
serous tumours showed negative MDM2 in 72.7% of cases (P value of Z test =0.04).
CONCLUSIONS: Alterations in the expression of the cell cycle regulator (MDM2)
occur early in the process of tumourigenesis in serous and mucinous ovarian
tumours. We suggest that MDM2 may be used in those tumours as a marker for risk
stratification and identification of cases with cancer development and
progression. We recommend further studies on MDM2 immunohistochemistry, in
conjunction with adjuvant methods as DNA ploidy and FISH gene amplification,
focusing on the mucinous tumours and differentiating between the three tumour
categories, benign, borderline and malignant.
PMID- 27509967
TI - Health Beliefs Associated with Cancer Screening Intentions in Korean Workers.
AB - BACKGROUND: Cancer is a leading cause of death in Korea. To prevent cancer, it is
essential to facilitate and promote appropriate cancer screening behavior in the
adult population. The aim of this study was to examine health beliefs related to
cancer screening intentions using the Health Belief Model (HBM). MATERIALS AND
METHODS: The research participants comprised 275 male health and safety managers
at commercial companies in Korea. The selfadministered survey explored
demographic characteristics, cancerrelated factors, beliefs about cancer/cancer
screening (BCCS) (vulnerability to cancer, severity of cancer, benefits of
screening, and barriers to screening), and cancer screening intention.
Multivariate logistic regression analyses were used to identify factors
associated with an intention to be screened for cancer. RESULTS: Perceived health
status and need for cancer prevention education were major factors associated
with BCCS. Poorer health status was associated with greater perceived
vulnerability, a perception of fewer benefits, and more barriers (p<0.05). A
perceived greater need for cancer prevention education was associated with a
higher perceived severity of cancer and more perceived barriers to screening
(p<0.05). Marital status, cancer screening experience, and perceived
vulnerability to cancer were significant influences on the cancer screening
intention (p<0.05). Participants who had undergone cancer screening in the past 2
years were more likely to intend to be screened for cancer than were those who
had not been screened; this was true across all degrees of intention and all
types of cancer (p<0.01). Hesitant people considered themselves less vulnerable
to gastric, lung, and liver cancer than did the poeple who intended to undergo
cancer screening (p<0.05). CONCLUSIONS: Based on our findings, we recommend that
workplace cancer prevention programs attempt to increase awareness about
vulnerability to cancer among workers who hesitate to undergo cancer screening.
PMID- 27509968
TI - Identification of a Novel Cassette Array in Integronbearing Helicobacter Pylori
Strains Isolated from Iranian Patients.
AB - Helicobacter pylori as the second most common cause of gastric cancer in the
world infects approximately half of the developed countries population and 80% of
the population living in developing countries. Integrons as genetic reservoirs
play major roles in dissemination of antimicrobial resistance genes. To the best
of our knowledge, this is the first study to report carriage of class 1 and 2
integrons and associated gene cassettes in H. pylori isolates from Iran. This
crosssectional study was conducted in Tehran among 110 patients with H. pylori
infection. Antimicrobial susceptibility testing (AST) for H. pylori strains were
assessed by the micro broth dilution method. Class 1 and 2 integrons were
detected using PCR. In order to determine gene cassettes, amplified fragments
were subjected to DNA sequencing of both amplicon strands. The prevalence of
resistance to clarithromycin, metronidazole, clarithromycin, tetracycline,
amoxicillin, rifampin, and levofloxacin were 68.2% (n=75), 25.5% (n=28), 24.5%
(n=27), 19.1% (n=21), 18.2% (n=20) and 16.4% (n=18), respectively. Frequency of
multidrug resistance among H. pylori isolates was 12.7%. Class 2 integron was
detected in 50 (45.5%) and class 1 integron in 10 (9.1%) H. pylori isolates. The
most predominant gene cassette arrays in class 2 integron bearing H. pylori were
included sateraaadA1, dfrA1sat2aadA1, blaoxa2 and, aadB whereas common gene
cassette arrays in class 1 integron were aadBaadA1cmlA6, aacA4, blaoxa2, and
catB3. The high frequency of class 2 integron and multidrug resistance in the
present study should be considered as a warning for clinicians that continuous
surveillance is necessary to prevent the further spread of resistant isolates.
PMID- 27509969
TI - Comparison of Two Step LEEP and Cold Conisation For Cervical Intraepithelial
Lesions to Decrease Positive Surgical Margins.
AB - PURPOSE: To assess the success rates of two step loop electrosurgical excision
procedure (LEEP) compared with conventional cold conization procedures for
decreasing positive surgical margins. MATERIALS AND METHODS: This study was
conducted on 70 patients who underwent colposcopic evaluation in Zeynep Kamil
Women and Children's Health Training and Research Hospital between 20132015 with
indications of CIN 2/3 or persistent CIN 1 for more than 2 years. The study
included age matched groups of patients with similar histopathololical lesions
who underwent cold conization (n=40) or LEEP (N=30). RESULTS: Comparison of
tissue characteristics between the two groups revealed significantly higher
deepest depth and lower volume of tissue removed by the two step LEEP.
Ectocervical positivity rate was similar between groups (1/39 versus 0/29,
P>0.05), while endocervical surgical margin positivity rate was significantly
higher in the cold conization group (9/39 versus 0/29, P<0.05). Surgical margin
positive cases were significantly older than the cases with negative margins
(P<0.05). CONCLUSIONS: Two step LEEP made it easier to reach the squamocolumnar
junction in the endocervical region with lower blood loss and applicability in
office settings. Our study suggests to use two step approach in cases with high
grade and glandular CIN.
PMID- 27509970
TI - Androgen Receptor Expression and its Correlation with Other Risk Factors in
Triple Negative Breast Cancers: a Report from Western Iran.
AB - BACKGROUND: Androgen receptors (ARs) are expressed in more than 70% of breast
cancers (BCs) and have been implicated in BC pathogenesis. Some triple negative
(TN)BC tumors express AR and may benefit from ARtargeted therapies. The aim of
this study was to evaluate survival and the prevalence of AR expression and its
correlation with other risk factors in triple negative BCs in women from Western
Iran. MATERIALS AND METHODS: In a retrospective study between 20092015, 41
patients with TNBC were referred to the Private Clinic of Oncology, Kermanshah
city, Iran. ER, PR and ARpositive expression was defined as >=10% nuclear
staining and also HER2 (2+), FISH was performed. Nuclear staining was considered
representative for Ki67 and P53. The mean followup for the patients was 25
months. In this time, 5 patients died and 4 lost to followup were censored from
survival analysis. RESULTS: The mean age at diagnosis was 46.9 years (range, 2471
years) and all patients were female. The OS rates for ARpositive and ARnegative
patients were 90% and 85.1%, respectively, and the mean OS was 26.3 and 23.2
months. Therefore, there was no significant difference between the two groups
(Hazard ratio: 0.580, 95% CI: 0.0863.893, P=0.575). CONCLUSIONS: In TNBC
patients, evaluation of AR status may provide additional information on prognosis
and treatment. The results of studies showed that the prevalence AR expression
may differ in the world and probably ethnicity can be an influencing factor.
PMID- 27509971
TI - Applicability of Oncoplastic Breast Conserving Surgery in Asian Breast Cancer
Patients.
AB - BACKGROUND: There are limited studies on oncoplastic breast conserving surgery in
Asian women. We aimed to determine the applicability and safety of oncoplastic
surgery, highlighting the specific circumstances when it will be most useful and
compare our preferred technique with the worldwide practice of oncoplastic
approaches. MATERIALS AND METHODS: Breast cancer patients who underwent
oncoplastic breast conserving surgery at a single institution from 1st May
201431st March 2015 were included. Data on patient demographics, tumor
characteristics and the type of oncoplastic surgery performed were collected.
RESULTS: Nineteen breast cancer patients were identified. 42.1% of patients had
grade I ptosis. The indications for surgery included a large tumor to breast size
ratio (52.6%), multifocal/multicentric lesions (36.8%) and asymmetric breasts
(10.6%), averting a mastectomy in 89.4%. Round block was the commonest technique
in 63% of patients, in contrast to the inverted T pattern most frequently used in
renowned institutions in the West. Mean and median tumor size and weight of
specimen were 29.4/25mm (11 75mm) and 77g/64g (10 246g) respectively. Reexcision
rate was 10.5%. Complete mastectomy was performed for one patient. One patient
developed wound dehiscence which was treated conservatively. Cosmetic outcome was
rated as excellent/good by 94.7% of patients. The patients remained clinically
well after a median 16 months follow up. CONCLUSIONS: Oncoplastic breast
conserving surgery is useful in a specific subgroup of Asian patients with a
relatively small breast volume and minimal ptosis. Round block was the commonest
technique in our series, in contrast to the worldwide utility of oncoplastic
techniques. It is oncologically safe and has good cosmetic outcomes.
PMID- 27509972
TI - TALENs Construction: Slowly but Surely.
AB - Cancer is thought to be a direct result of transcriptional misregulation. Broad
analysis of transcriptional regulatory elements in healthy and cancer cells is
needed to understand cancer development. Nucleases regulatory domains are
recruited to bind and manipulate a specific genomic locus with high efficacy and
specificity. TALENs (transcription activatorlike effector nuclease) fused to
endonuclease FokI have been used widely to target specific sequences to edit
several genes in healthy and cancer cells. This approach is promising to target
specific cancer genes and for this purpose it is needed to pack such TALENs into
viral vectors. There are some considerations which control the success of this
approach, targeting appropriate sequences with efficient construction of TALENs
being crucial factors. We face some obstacles in construction of TALENs; in this
study we made a modification to the method of Cermk et al 2011 and added one step
to make it easier and increase the availability of constructs.
PMID- 27509973
TI - Roles of CYP1A1 and CYP2E1 Gene Polymorphisms in Oral Submucous Fibrosis.
AB - BACKGROUND: Oral submucous fibrosis (OSF) is a precancerous condition with a 4
to13% malignant transformation rate. Related to the habit of areca nut chewing it
is mainly prevalent in Southeast Asian countries where the habit of betel quid
chewing is frequently practised. On chewing, alkaloids and polyphenols are
released which undergo nitrosation and give rise to Nnitrosamines which are
cytotoxic agents. CYP450 is a microsomal enzyme group which metabolizes various
endogenous and exogenous chemicals including those released by areca nut chewing.
CYP1A1 plays a central role in metabolic activation of these xenobiotics, whereas
CYP2E1 metabolizes nitrosamines and tannins. Polymorphisms in genes that code for
these enzymes may alter their expression or function and may therefore affect an
individuals susceptibility regarding OSF and oral cancer. The present study was
therefore undertaken to investigate the association of polymorphisms in CYP1A1 m2
and CYP2E1 (RsaI/PstI) sites with risk of OSF among areca nut chewers in the
Northern India population. A total of 95 histopathologically confirmed cases of
OSF with history of areca nut chewing not less than 1 year and 80, age and sex
matched controls without any clinical signs and symptoms of OSF with areca nut
chewing habit not less than 1 year were enrolled. DNA was extracted from
peripheral blood samples and polymorphisms were analyzed by PCRRFLP method. Gene
polymorphism of CYP1A1 at NcoI site was observed to be significantly higher (p =
0.016) in cases of OSF when compared to controls. Association of CYP1A1 gene
polymorphism at NcoI site and the risk of OSF (Odd's Ratio = 2.275) was also
observed to be significant. However, no such association was observed for the
CYP2E1 gene polymorphism (Odd's Ratio = 0.815). Our results suggest that the
CYP1A1 gene polymorphism at the NcoI site confers an increased risk for OSF.
PMID- 27509974
TI - Systematic Review of Smoking Initiation among Asian Adolescents, 20052015:
Utilizing the Frameworks of Triadic Influence and Planned Behavior.
AB - BACKGROUND: A recent WHO data report on mortality attributable to tobacco use
including cigarette smoking indicated a very high burden of deaths in Asia and
that people often initiate smoking as early as young adolescents. The objectives
of this study were to systematically review peerreviewed articles on cigarette
smoking initiation among Asian adolescents and to develop a conceptual model of
factors influencing smoking initiation by integrating all relevant factors based
on existing data. MATERIALS AND METHODS: Following a PRISMA guideline, a
systematic review of articles published between 2005 and June 2015 was conducted
using 5 databases on cigarette smoking initiation among adolescents (aged 1019
years) living in Asia. We summarized the main findings of each study according to
our research questions and data that emerged during the data extraction process.
Analysis and categorization were based on the TTI and TPB models and
classification of factors extracted from the study, were as follows: personal
factors, social factors, broader environmental factors, mediators, and intention
to initiate smoking and smoking behavior. RESULTS: Of 1,227 identified studies,
only 20 were included in this review. Our findings found that the mean age of
cigarette smoking initiation ranged from 10 to 14 years and those who are more
likely to initiate smoking are male, older adolescents, adolescents with low
parental SES, individuals with low parental monitoring, low parental education
level and having no discussion on smoking at home, those living in public housing
and those exhibiting healthrisk behavior. Our study also revealed that the risk
of smoking initiation increased when they are exposed to smokers, influenced by
peers, exposed to tobacco advertisements, receive pocket money, have lack of
knowledge about smoking, have poor school performance, have a family conflict and
have psychological problems. The conceptual model developed demonstrated complex
networks of factors influencing initiation. CONCLUSIONS: This systematic review
presents various factors influencing smoking initiation of the Asian adolescents
and provides a conceptual framework to further analyze factors. Future studies
should have a standard measure of smoking initiation, should analyze interactions
and the intensity of relationships between different factors or variables in the
conceptual model. This will in turn consolidate the understanding of the
different factors affecting smoking initiation and will help to improve
interventions in this area.
PMID- 27509975
TI - Ultrasonographic Features of Medullary Thyroid Carcinoma: Do they Correlate with
Pre and PostOperative Calcitonin Levels?
AB - PURPOSE: To correlate ultrasonographic (US) features of medullary thyroid
carcinoma (MTC) with pre operative and postoperative calcitonin levels. MATERIALS
AND METHODS: A total of 130 thyroid nodules diagnosed as MTC were evaluated. Two
radiologists retrospectively evaluated preoperative US features according to
size, shape, margin, echogenicity, type of calcification, and lymph node status.
Postoperative clinical and imaging followup (mean duration 31.9 +/- 22.5 months)
was performed for detection of tumor recurrence. US features, presence of LN
metastasis, and tumor recurrence were compared between MTC nodules with and
without elevated preoperative calcitonin (>100 pg/mL). Those with normalized and
nonnormalized postoperative calcitonin levels groups were also compared. RESULTS:
Common US features of MTCs were solid internal content (90.8%), irregular shape
(44.6%), circumscribed margin (46.2%), and hypoechogenicity (56.2%). Comparing
MTC nodules with and without elevated preoperative calcitonin levels, the size
and shape of MTC nodule and lymph node metastasis showed statistical significance
(p<0.05). Postoperative calcitonin normalization correlated with US features of
tumor size (p=0.002), margin (p=0.034), shape (p<=0.001), and presence of
calcification (p=0.046). Tumor recurrence and LN metastasis were more prevalent
in patients without normalization of postoperative calcitonin than in those with
normalization (p=0.001). CONCLUSIONS: Serum calcitonin measurement is helpful for
early diagnosis and predicting prognosis. Postoperative calcitonin measurement is
also important for postoperative US follow up, especially in cases with larger
nodule size, presence of calcification, irregular shape, and irregular margin.
PMID- 27509976
TI - Correlation of Hormone Receptor and HER2/neu Expression with Clinicopathologic
Parameters in Primary Breast Tumors.
AB - BACKGROUND: Breast cancer (BC) is a major health issue worldwide as well as in
Pakistan. All women belonging to any race, ethnicity or lineage are in danger of
developing breast cancer. Significant factors influencing the development of
breast malignancies are the genetic background, environmental conditions,
reproductive parameters, the consequences of female hormones both intrinsic and
extrinsic, alteration of immune status, and biologic determinants. MATERIALS AND
METHODS: Overall 150 biopsy proven patients were included in the study. Samples
were submitted for histopathology and determination of estrogen and progesterone
receptor expression and HER2/neu status. Associations with other characteristics
like age, tumor stage, node involvement, histological grade were also studied.
RESULTS: Mean age at presentation was 46.7 years. The majority had invasive
ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important
relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu
overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2
neu and tumor grade, stage, age, lymph node involvement except for the menopausal
status. CONCLUSIONS: In summary, breast cancer patients featured an advanced
stage of disease, more lymph node involvement, and moderately high grade tumors
and with more estrogen, progesterone receptor and HER2 positive tumors.
PMID- 27509977
TI - Combined Genotype Analyses of Precursor miRNA196a2 and 499a Variants with Hepatic
and Renal Cancer Susceptibility a Preliminary Study.
AB - MicroRNAs, a novel class of small noncoding RNAs, are key players in many
cellular processes, including cell proliferation, differentiation, invasion and
regeneration. Tissue and circulatory microRNAs could serve as useful clinical
biomarkers and deregulated expression levels have been observed in various
cancers. Gene variants may alter microRNA processing and maturation. Thus, we
aimed to investigate the association of MIR196a2 rs11614913 (C/T), MIR499a
rs3746444 (A/G) polymorphisms and their combination with cancer susceptibility in
an Egyptian population. Sixty five renal cell carcinoma (RCC) and 60
hepatocellular carcinoma (HCC) patients and 150 controls were enrolled in the
study. They were genotyped using realtime polymerase chain reaction technology.
Both miR196a2*T and miR499a*G were associated with RCC risk, but only miR196a*T
was associated with HCC development. Carriage of the homozygote combinations
(MIR196a2*TT + MIR499a*AA) and (MIR196a2*CC + MIR499a*GG) was associated with 25
and 48 fold elevation of likelhood to develop RCC, respectively. The miR196a2 SNP
was also linked with larger tumor size in RCC and advanced tumor stage in HCC.
miR196a2 and miR499a combined genotypes were associated with RCC and HCC. Further
functional analysis of SNPs is required to confirm relationships between
genotypes and phenotypes.
PMID- 27509978
TI - Clinical Features of Lung Cancer in Japanese Patients Aged Under 50.
AB - The proportion of lung cancer patients under 50 years old is small at
approximately 510%, but as with patients older than 50, the number is on the
rise. Although lung cancer treatment strategies have undergone extensive
transformation in recent years based on the presence or absence of oncogenic
driver mutations, there are few reports regarding these mutations in the young or
the relationship between clinical setting and prognosis. Therefore, we conducted
a study of clinical features in 36 patients under the age of 50 who were
diagnosed with primary lung cancer from October 2008 to November 2015. The 22
patients in stages I through III A underwent operations, and all 17 whose lung
cancer were detected through screening were candidates for surgery. Gene analysis
was conducted for 26 (72.2%); 10 (38.5%) were positive for EGFR gene mutations,
and ALK gene translocation was present in 4 (15.4%). In stage IV patients, the
median progression free survival (PFS) in the ALK translocation positive and
negative patients was 518 days and 130 days, respectively, and the median overall
survival (OS) was not reached and 280 days, respectively. A trend toward extended
PFS (p=0.203) and OS (p=0.056) was observed in patients positive for ALK
translocation. We must strive for early detection by increasing screening rates
and evaluate oncogenic driver mutations important for prognosis of lung cancer in
the young.
PMID- 27509979
TI - Tumor Necrosis Factor Alpha 308 G/A Single Nucleotide Polymorphism and
Susceptibility to Hepatocellular Carcinoma Via Hepatitis B Infection.
AB - BACKGROUND: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma
(HCC). About 350 million people are affected by chronic infection which is
related to the rapid development of liver diseases as well as hepatitis,
cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha
(TNFalpha) in the liver demonstrates a major genetic polymorphism which is
involved in resistance or susceptibility to chronic HBV infection. MATERIALS AND
METHODS: In this study, two populations were studied by the sequence specific
primerpolymerase chain reaction (SSPPCR) method: HBV cases (n=409), who were
HBSAg+, and healthy controls (n=483). RESULTS: The results shown that the
frequency of TNFalpha 308 G/G genotype in healthy controls (47.2%) was
significantly higher than in HBV infected patients (28%) (CI = 1.292.61, OR =
1.83, P = 0.0004). Also TNFalpha 308 A/A and A/G genotype frequencies in the
healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5%
(CI = 2.237.12, p: 0.0001, OR: 3.94) respectively. CONCLUSIONS: We found that
among Iranian people TNFalpha 308A allele not only has the highest genotype
frequency but also it has the highest frequency in the world population. In
addition, TNFalpha308 G/G polymorphism was associated with HBV resistance,
whereas TNFalpha308A (A/A or A/G) polymorphism appeared to associated with
chronic HBV infection. These data suggested that among the Iranian population,
the 308 G/G polymorphism of TNFalpha gene promoter region has the potential to
influence the susceptibility to HBV infection and it may be responsible for viral
antigen clearance.
PMID- 27509980
TI - Efficacy of Using Sequential Primary Circulating Prostate Cell Detection for
Initial Prostate Biopsy in Men Suspected of Prostate Cancer.
AB - BACKGROUND: Sequential use of circulating prostate cell (CPC) detection has been
reported to potentially decrease the number of unnecessary prostate biopsies in
men suspected of prostate cancer. In order to determine the real world
effectiveness of the test, we present a prospective study of men referred to two
hospitals from primary care physicians, one using CPC detection to determine the
necessity of prostate biopsy the other not doing so. MATERIALS AND METHODS: Men
with a suspicion of prostate cancer because of elevated PSA >4.0ng/ml or abnormal
DRE were referred to Hospitals A or B. In Hospital A all underwent 12 core TRUS
biopsy, in Hospital B only men CPC (+), with mononuclear cells obtained by
differential gel centrifugation identified using double immunomarking with
antiPSA and antiP504S, were recommended to undergo TRUS biopsy. Biopsies were
classifed as cancer or nocancer. Diagnostic yields were calculated, including the
number of posible biopsies that could be avoided and the number of clinically
significant cancers that would be missed. RESULTS: Totals of 649 men attended
Hospital A, and 552 men attended Hospital B; there were no significant
differences in age or serum PSA levels. In Hospital A, 228 (35.1%) men had
prostate cancer detected, CPC detection had a sensitivity of 80.7%, a specificity
of 88.6%, and a negative predictive value of 89.5%. Some 39/44 men CPC negative
with a positive biopsy had low grade small volume tumors. In Hospital B, 316
(57.2%) underwent biopsy. There were no significant differences between
populations in terms of CPC and biopsy results. The reduction in the number of
biopsies was 40%. CONCLUSIONS: The use of sequential CPC testing in the real
world gives a clear decision structure for patient management and can reduce the
number of biopsies considerably.
PMID- 27509981
TI - TLR1 Polymorphism Associations with Gastric Mucosa Morphologic Patterns on
Magnifying NBI Endoscopy: a Prospective CrossSectional Study.
AB - BACKGROUND: Helicobacter pylori is now recognized as a causative factor of
chronic gastritis, gastroduodenal ulcers, gastric cancer and mucosaassociated
lymphatic tissue lymphoma. Tolllike receptors are important bacterial receptors
in gastric epithelial cell signaling transduction and play critical roles in
gastric carcinogenesis. MATERIALS AND METHODS: A total of 400 patients undergoing
esophagogastroduodenoscopy for investigation of chronic abdominal pain were
genotyped for singlenucleotide polymorphisms (SNPs) in TLR1 (rs4833095) using
TagMan SNPs genotyping assay by realtime PCR hybridization. Relationships with
susceptibility to H. pylori infection and premalignant gastric mucosa
morphological patterns, classified by magnifying NBI endoscopy, were
investigated. RESULTS: The percentages of TLR1 rs4833095, CC homozygous, CT
heterozygous and TT homozygous cases were 34, 46.5 and 19%, respectively. CC
showed statistical differences between H. pylori positive and negative cases
(P<0.001). CT and TT correlated with type 1 and type 2 gastric mucosal
morphological patterns (P<0.01) whereas CC correlated with types 3 and 4
(P<0.01). CONCLUSIONS: This study demonstrated good correlation of TLR1 rs4833095
genotype with severity of inflammation in H. pylori infected gastric mucosa
according to gastric mucosal morphologic patterns with magnifying NBI endoscopy.
PMID- 27509982
TI - Probiotic Conjugated Linoleic Acid Mediated Apoptosis in Breast Cancer Cells by
Downregulation of NFkappaB.
AB - Conjugated linoleic acid, a functional lipid, produced from Lactobacillus
plantarum (LPCLA), has been demonstrated to possess apoptotic activity. The
antiproliferative and apoptotic potential of LPCLA was here evaluated in vitro
using the MDAMB231 human breast cancer cell line as a model system. Proliferation
of MDA MB231 cells was inhibited with increasing concentrations of LPCLA with
altered morphological features like cell detachment, rounding of cells and
oligonucleosomal fragmentation of DNA. Flow cytometry confirmed the apoptotic
potential of LPCLA by ANNEXIN V/PI double staining. Furthermore, outcome results
indicated that the apoptosis was mediated by downregulation of the NF?B pathway
which in turn acted through proteasome degradation of I?Balpha, inhibition of p65
nuclear translocation, release of cytochromeC from mitochondria and finally
overexpression of Bax protein. Thus, conjugated linoleic acid, a natural product
derived from probiotics, could therefore be a possible potential chemotherapeutic
agent due to its apoptotic activity against estrogen receptor negative breast
cancer cells.
PMID- 27509983
TI - Calpeptin Prevents Malignant Pleural Mesothelioma Cell Proliferation via the
Angiopoietin1/Tie2 System.
AB - Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of
mesothelial origin associated with asbestos exposure, shows a limited response to
conventional chemotherapy and radiotherapy. Therefore, the overall survival of
MPM patients remains very poor. Progress in the development of therapeutic
strategies for MPM has been limited. We recently reported that the calpain
inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by
inhibiting the proliferation of lung fibroblasts. In the present study, we
examined the preventive effects of calpeptin on the cell growth of MPM, the
origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin
inhibited the proliferation of MPM cells, but not mesothelial cells. It also
prevented 1) the expression of angiopoietin (Ang)1 and Tie2 mRNA in MPM cells,
but not mesothelial cells and 2) the Ang1induced proliferation of MPM cells
through an NFkB dependent pathway, which may be the mechanism underlying the
preventive effects of calpeptin on the growth of MPM cells. These results suggest
potential clinical use of calpeptin for the treatment of MPM.
PMID- 27509984
TI - Expression of Epstein Barr Virus Encoded EBNA1 and LMP1 Oncoproteins in
Nasopharyngeal Carcinomas from Northeast India.
AB - BACKGROUND: Nasopharyngeal carcinoma (NPC), a malignancy arising from the
epithelial lining of the nasopharynx, is distinct from others cancers in terms of
its epidemiologic features. It is rare in most parts of the world except for a
few regions with populations of Mongoloid origin. OBJECTIVES: To study the
expression pattern of Epstein Barr virus (EBV) encoded oncoproteins EBNA1 and
LMP1 in different histological types of NPC and to correlate expression patterns
with sex, age and histological types. MATERIALS AND METHODS: A total of 40
formalinfixed, paraffinembedded NPC biopsy samples and tissues from 20 healthy
controls were collected to study the expression level of EBNA1 and LMP1 using
immunohistochemistry. RESULTS: EBNA1 and LMP1 expression was found in 92.5% and
90% respectively, of the cases and none of the control specimens. The expression
patterns of EBNA1 and LMP1 were determined to be statistically significant
(p<0.05) when correlated with sex, age and histological distributions. Also
immunohistochemistry was found to be a sensitive technique in the detection of
EBV. CONCLUSIONS: The study reveals that the potent oncoproteins EBNA1 and LMP1
were over expressed in our population cohort. Our findings are to some extent
inconsistent with earlier reports as our population showed a higher expression of
both EBNA1 and LMP1 compared to other studies.
PMID- 27509985
TI - Clinicopathological Features and Survival Rate of Colorectal Adenocarcinoma
Patients with and without a KRAS Mutation: a FiveYear Study in Yazd, Iran.
AB - BACKGROUND: By some estimates, colorectal carcinoma is the third most common
cancer worldwide. The most appropriate method of treatment, especially of its
metastatic form, is determined based on KRAS status. The present study was
conducted on patients with colorectal cancer positive or neagtive for a KRAS
mutation in terms of survival rate and the response to treatment. MATERIALS AND
METHODS: Medical records of all cases with colorectal cancer hospitalized from
2010 to 2015 and with KRAS testing results were studied. Data such as gender,
age, tumor (size, grade, location, stage), treatment type, KRAS status and
survival were considered as variables. Survival analysis was performed using the
KaplanMeier method and Logrank test. Statistical significance level was defined
as P value <0.05. RESULTS: Out of 90 patients, 55 (61.2%) were male and 35(38.8%)
were female with the age range of 2287 years. The overall disease specific
survival was 53+/-3 (Mean +/- SE) months with 95%CI:4760, and there were
statistically significant differences between the mean survival rate with tumor
stage and the response to treatment (log rank test, PV=0.007 and PV=0.001)
respectively. The risk of mortality was 2.02 times higher in patients with mutant
KRAS compared to those with the wild type of the gene; however, this difference
was not statistically significant (OR=2.016; 95%CI: 0.685.9; PV=0.197).
CONCLUSIONS: In our study the overall 5year disease specific survival rate was
low as compared to similar studies elsewhere. Significant correlations were found
between survival time with treatment type and tumor stage.
PMID- 27509986
TI - Cancer Patients Are at High Risk of Mortality if Presenting with Sepsis at an
Emergency Department.
AB - BACKGROUND: Sepsis is an emergency condition with high mortality and morbidity
rate. There are limited data on the association of cancer as a risk factor for
mortality in sepsis patients in the emergency department (ED). MATERIALS AND
METHODS: This retrospective study was conducted at the ED, Faculty of Medicine,
Ramathibodi Hospital, Bangkok, Thailand. The study period was between January 1st
and December 31st, 2014. The inclusion criteria were as follows: adult patients
over 15 years of age who presented at the ED with suspicion of sepsis, received
treatment at the ED, and whose blood culture was found to be positive. Clinical
data were recorded from medical records including the Mortality in Emergency
Department Sepsis score (MEDS score). The primary outcome of this study was
mortality at one month. Multivariate logistic regression analysis was used to
identify independent factors associated with death. RESULTS: During the study
period, there were 775 eligible patients. The two most common pathogens
identified from blood cultures were Staphylococcus aureus (193 patients; 24.9%)
and Escherichia coli (158 patients; 20.4%). At one month after presenting at the
ED, 110 patients (14.2%) had died. There were four significant factors for death,
having cancer, being on an endotracheal tube, initial diagnosis of bacteremia,
and high MED scores. Having cancer had an adjusted OR of 2.12 (95% CI of 1.29,
3.47). CONCLUSIONS: Cancer patients have double the risk of mortality if
presenting with sepsis at the ED.
PMID- 27509987
TI - Severe Manifestations and Grave Prognosis in Young Patients with Gastric Cancer
in Thailand.
AB - BACKGROUND: Gastric cancer is the second leading cause of cancer death worldwide
and occurs most frequently in the age group of 5070 years. Rarely reports have
appeared regarding younger age groups. The purpose of this study was to compare
clinical characteristics and outcome of treatment between young and elderly
patients with gastric cancer in Thailand. MATERIALS AND METHODS: Clinical
information, histological features, endoscopic findings and treatment outcome
were reviewed and collected from Thammasat University Hospital, Pathumthani and
Bangkok Medical Center, Bangkok, Thailand between September 2011March 2015.
RESULTS: A total of 154 gastric tumor patients including 101 with benign tumors
(22 males and 79 females, mean age= 62.6 years) and 53 with gastric cancers (27
males and 26 females, mean age= 60.6 years) were enrolled in this study. Gastric
cancer patients presented with alarm symptoms such as anemia, anorexia and weight
loss significantly more frequently than benign gastric tumor patients. In gastric
cancer patients, mean duration of symptoms prior to diagnosis was shorter in
younger (<40 years) than older patients (age >=40 years) (73.3 days vs 84.8
days). Family history of GI malignancy and diffuse type of gastric cancer were
significant greater in younger than older patients (36% vs 5% P=0.01; OR= 11.4,
95%CI = 1.874.7 and 73% vs 14%, P<0.01; OR= 16, 95%CI = 3.378, respectively) and
5year survival rates were 9% in younger age patients and 19% in older age group.
CONCLUSIONS: Most young patients with gastric cancer in Thailand feature
aggressive manifestations with poorer prognosis than elderly patients. Early
detection of gastric cancer in high risk young patients might be important key to
improve survival rate and treatment outcome in this particular group.
PMID- 27509988
TI - Expression Levels of Tetraspanin KAI1/CD82 in Breast Cancers in North Indian
Females.
AB - BACKGROUND: Carcinogenesis is a multifaceted intricate cellular mechanism of
transformation of the normal functions of a cell into neoplastic alterations.
Metastasis may result in failure of conventional treatment and death Hence,
research on metastatic suppressors in cancer is a high priority. The metastatic
suppressor gene CD82, also known as KAI1, is a member of the transmembrane 4
superfamily which was first identified in carcinoma of prostate. Little work has
been done on this gene in breast cancer. Herein, we aimed to determine the gene
and protein level expression of CD82/KAI1 in breast cancer and its role as a
prognosticator. MATERIALS AND METHODS: In this study, 83 histologically proven
cases of breast cancer and a similar number of controls were included. Patient
age ranged from 1870 years. Quantitative Real Time Polymerase Chain Reaction (qRT
PCR) and immunohistochemistry (IHC) were used to investigate KAI1 expression at
gene and protein levels, respectively. Statistical analysis was done to correlate
expression of KAI1 and clinicopathological parameters. RESULTS: It was revealed
that: (i) KAI1 was remarkably diminished in metastatic vs non metastatic breast
cancer both at the gene and the protein levels (P<.05); (ii) KAI1 expression
levels were strongly correlated with TNM staging, histological grade and advanced
stage (p<0.001) and no association was found with any other studied parameter;
(iii) Lastly, a significant correlation was observed between expression of KAI1
and overall median survival of BC patients (P = 0.04). CONCLUSIONS: Our results
suggest that lack of expression of the KAI1 might indicate a more aggressive form
of breast cancer. Loss of KAI1 may be considered a significant prognostic marker
in predicting metastatic manifestation. When evaluated along with the clinical
and pathological factors, KAI1 expression may be beneficial to tailor aggressive
therapeutic strategies for such patients.
PMID- 27509990
TI - Risk Factors for Gallbladder Cancer in Nepal a Case Control Study.
AB - BACKGROUND: Gall bladder cancer (GBC) is highly fatal disease with poor
prognosis, with a 5 year survival rate of <10%. It is relatively rare cancer
worldwide; however it is the sixth cancer and second most common gastrointestinal
tract cancer in Nepalese women. The study focused on associations of certain
demographic, lifestyle, dietary, and reproductive factors with gall bladder
cancer. MATERIALS AND METHODS: We conducted a hospitalbased matched case control
study on newly diagnosed cases of primary GBC at BP Koirala Institute of Health
Sciences and BP Koirala Memorial Cancer Hospital. Controls were healthy nonGBC
relatives of cancer patients, matched for age, sex and marital status (in case of
females) with cases at a ratio of 1:2. Data were collected between April
2012April 2013 by semi structured interview from both cases and controls.
Analyses were carried out with SPSS. Conditional logistic regression was used to
find odds ratios and 95% confidence intervals for bivariate and multivariate
analysis. RESULTS: A total of 50 cases and 100 controls were enrolled in this
study. On bivariate analysis, factors found to be significantly associated with
gallbladder cancer were illiteracy (OR= 3.29, CI= 1.0610.2), history of gallstone
disease (OR=27.6, CI=6.57, 115.6), current smoker (OR=2.42, CI=1.005 5.86), early
menarche <13 years (OR=2.64, CI=1.096.44), high parity more than 3 (OR=3.12,
CI=1.25,7.72), and use of mustard oil (OR=3.63, CI=1.40, 9.40). A significant
protective effect was seen with high consumption of fruits at least once a week
(OR=0.101, CI=0.030.35). On multivariate analysis, history of gallstone disease,
early menarche, current smoker and high consumption of fruits persisted as
significant factors. CONCLUSIONS: History of gallstone disease, cigarette smoking
and early menarche were associated with increased risk of gallbladder cancer
while high consumption of fruits was found to have a protective effect.
PMID- 27509989
TI - Roles of MicroRNA21 and MicroRNA29a in Regulating Cell Adhesion Related Genes in
Bone Metastasis Secondary to Prostate Cancer.
AB - BACKGROUND: There is an increasing concern in the role of microRNA (miRNA) in the
pathogenesis of bone metastasis (BM) secondary to prostate cancer (CaP). In this
exploratory study, we hypothesized that the expression of vinculin (VCL) and
chemokine X3C ligand 1 (CX3CL1) might be downregulated in clinical samples, most
likely due to the posttranscriptional modification by microRNAs. Targeted genes
would be upregulated upon transfection of the bone metastatic prostate cancer
cell line, PC3, with specific microRNA inhibitors. MATERIALS AND METHODS:
MicroRNA software predicted that miR21 targets VCL while miR29a targets CX3CL1.
Twenty benign prostatic hyperplasia (BPH) and 16 high grade CaP formalinfixed
paraffin embedded (FFPE) specimens were analysed. From the bone scan results,
high grade CaP samples were further classified into CaP with no BM and CaP with
BM. Transient transfection with respective microRNA inhibitors was done in both
RWPE1 (normal) and PC3 cell lines. QPCR was performed in all FFPE samples and
transfected cell lines to measure VCL and CX3CL1 levels. RESULTS: QPCR confirmed
that VCL messenger RNA (mRNA) was significantly down regulated while CX3CL1 was
upregulated in all FFPE specimens. Transient transfection with microRNA
inhibitors in PC3 cells followed by qPCR of the targeted genes showed that VCL
mRNA was significantly up regulated while CX3CL1 mRNA was significantly
downregulated compared to the RWPE1 case. CONCLUSIONS: The downregulation of VCL
in FFPE specimens is most likely regulated by miR21 based on the in vitro
evidence but the exact mechanism of how miR21 can regulate VCL is unclear.
Upregulated in CaP, CX3CL1 was found not regulated by miR29a. More microRNA
screening is required to understand the regulation of this chemokine in CaP with
bone metastasis. Understanding miRNAmRNA interactions may provide additional
knowledge for individualized study of cancers.
PMID- 27509991
TI - AgeStandardized Incidence Rates and Survival of Osteosarcoma in Northern
Thailand.
AB - Osteosarcoma is a common primary malignant bone tumor in children and
adolescents. Recent worldwide average incidences of osteosarcoma in people aged 0
to 24 years were 4.3 and 3.4 per million, respectively, with a ratio of 1.4:1.
However, data on the incidence of osteosarcoma in Thailand are limited. This
study analyzed the incidence of osteosarcoma in the upper northern region of
Thailand, with a population of 5.85 million people (8.9% of the total Thai
population), using data for the years 1998 to 2012, obtained from the Chiang Mai
Cancer Registry (CMCR) at Chiang Mai University Hospital and the Lampang Cancer
Registry (LCR) at the Lampang Cancer Hospital, a total of 144 cases. The overall
annual incidence of osteosarcoma was 1.67 per million with a male:female ratio of
1.36:1. Incidences by age group (male and female) at 0 to 24, 25 to 59 and over
60 years were 3.5 (3.9 and 3.0), 0.8 (0.9 and 0.6), and 0.7 (0.8 and 0.5),
respectively. The peak incidence occurred at 15 to 19 years for males and at 10
to 14 years for females. The median survival time was 18 months with a 5year
survival rate of 43%. Neither the age group nor the 5year interval period of
treatment was significantly correlated with survival during the 15year period
studied.
PMID- 27509992
TI - Challenges in the Management of Breast Cancer in a Low Resource Setting in South
East Asia.
AB - BACKGROUND: Breast cancer is the second most common cancer in women in Cambodia,
a low income country in SouthEast Asia. The Sihanouk Hospital Centre of Hope
(SHCH) is a charity hospital set up by an international nongovernmental
organisation, HOPE Worldwide. In 2008, SHCH partnered with AmeriCares, a global
health organisation to set up and deliver a breast cancer programme to provide
education, diagnosis and treatment for women with breast cancer. The objective of
this study is to characterise the presentation, diagnosis, treatment and outcomes
of women treated under this program. MATERIALS AND METHODS: A total of 215 women
newly diagnosed with breast cancer from 1 March 2008 until 31 March 2011 were
studied. Age at diagnosis, tumour size, histological type, tumour grade, ER,
lymph node involvement, treatment modalities (surgery, radiotherapy,
chemotherapy, hormone therapy) were recorded. Data on mortality at 3 years were
obtained whenever possible. RESULTS: The median age was 47 years old. Some 77.8%
were diagnosed with stage 3 and 4 lesions, and 78.5% underwent mastectomy, of
which 28.4% the intent was palliative. Of those whose ER status were known, only
48.3% were ER positive. Only 6 patients could afford chemotherapy while only 1
patient had radiotherapy. Hormone therapy was provided free for those who were ER
positive. The overall survival rate at 3 years was 39.1%. CONCLUSIONS: Breast
cancer presents at a late stage, and because treatment is suboptimal, survival is
poor in Cambodia. A more aggressive approach to early detection and treatment
needs to be developed to improve outcome from this potentially curable disease.
PMID- 27509994
TI - Global Sex Differences in Cancer Mortality with Age and Country Specific
Characteristics.
AB - BACKGROUND: The cancer research literature suggests that women, especially
premenopausal women, have lower cancer mortality rates than men. However, it is
unclear if that is true for populations at all age levels in all countries and
what factors affect such sex differences. This paper attempts to fill that gap.
MATERIALS AND METHODS: Sex and countryspecific cancer mortality data were
statistically analyzed with particular attention to geographic, social, and
economic factors that may affect the sex differences. RESULTS: The sex
differences were age and country specific, rather than universal. Premenopausal
women actually tend to have a disadvantage compared to men or postmenopausal
women. Male cancer mortality appears to be the affecting factor in explaining
variations in sex differences. Latitude of residence and literacy rate are the
affecting factors in cancer mortality and sex differences. African and Latin
American countries tend to have a female disadvantage, while East Asian and
Eastern European countries are more likely to have a female advantage.
CONCLUSIONS: The findings challenge the cancer mortality literature and indicate
that the sex differences and their possible causes are more complicated than the
current literature suggests. They also highlight the urgency of adapting age and
country specific health systems and policies to better meet the needs of younger
women.
PMID- 27509993
TI - Significantly Low Effective Dose from 18FDG PET/CT Scans Using Dose Reducing
Strategies: "Lesser is Better".
AB - BACKGROUND: Fluorodeoxyglucose (18FDG) PET/CT imaging has become an important
component of the management paradigm in oncology. However, the significant
imparted radiation exposure is a matter of growing concern especially in younger
populations who have better odds of survival. The aim of this study was to
estimate the effective dose received by patients having whole body 18FFDG PET/CT
scanning as per recent dose reducing guidelines at a tertiary care hospital.
MATERIALS AND METHODS: This prospective study covered 63 patients with different
cancers who were referred for PET/CT study for various indications. Patients were
prepared as per departmental protocol and 18FDG was injected at 3 MBq/Kg and a
low dose, nonenhanced CT protocol (LD NECT) was used. Diagnostic CT studies of
specific regions were subsequently performed if required. Effective dose imparted
by 18FDG (internal exposure) was calculated by using multiplying injected dose in
MBq with coefficient 1.9?102 mSv/MBq according to ICRP publication 106. Effective
dose imparted by CT was calculated by multiplying DLP (mGy.cm) with ICRP
conversion coefficient "k" 0.015 [mSv / (mG. cm)]. RESULTS: Mean age of patients
was 49 +/-18 years with a male to female ratio of 35:28 (56%:44%). Median dose of
18FDG given was 194 MBq (range: 139293). Median CTDIvol was 3.25 (2.46.2) and
median DLP was 334.95 (246.70 576.70). Estimated median effective dose imparted
by 18FDG was 3.69 mSv (range: 2.855.57). Similarly the estimated median effective
dose by low dose (nondiagnostic) CT examination was 4.93 mSv (range: 2.14 10.49).
Median total effective dose by whole body 18FDG PET plus low dose nondiagnostic
CT study was 8.85 mSv (range: 5.5613.00). CONCLUSIONS: We conclude that the
median effective dose from a whole body 18FDG PET/CT in our patients was
significantly low. We suggest adhering to recently published dose reducing
strategies, use of ToF scanner with CT dose reducing option to achieve the lower
if not the lowest effective dose. This would certainly reduce the risk of second
primary malignancy in younger patients with higher odds of cure from first
primary cancer.
PMID- 27509995
TI - Gene Expression of CYP1A1 and its Possible Clinical Application in Thyroid Cancer
Cases.
AB - BACKGROUND: Thyroid cancer is the most common endocrine malignancy, and exact
causes remain unknown. The role of CYP450 1A1 (CYP1A1) in cancer initiation and
progression has been investigated. The aim of this work was to analyze, for the
first time, CYP1A1 gene expression and its relationship with several
clinicopathological factors in Mexican patients diagnosed with thyroid cancer.
MATERIALS AND METHODS: Realtime PCR analysis was conducted on 32 sets of thyroid
tumors and benign pathologies. Expression levels were tested for correlations
with clinical and pathological data. All statistical analysis were performed
using GraphPad Prism version 3.0 software. RESULTS: We found that female gender
was associated with thyroid cancer risk (P<0.05). A positive relationship was
identified between CYP1A1 mRNA levels and the presence of chronic disease,
alcohol use, tumor size, metastasis and an advanced clinical stage (P<0.05).
CONCLUSIONS: The results suggest that CYP1A1 gene expression could be used as a
marker for thyroid cancer.
PMID- 27509996
TI - Reasons and Motivations for Cigarette Smoking and Barriers against Quitting Among
a Sample of Young People in Jeddah, Saudi Arabia.
AB - BACKGROUND: Cigarette smoking is one of the leading causes of death in the world.
Tobacco consumption has grave negative consequences for health so that it is
important to understand the reasons and motivations towards cigarette smoking and
barriers against quitting smoking among the young generation for developing
effective policies to control this widespread problem. MATERIALS AND METHODS:
This crosssectional survey was carried out at the Faculty of Medicine, Rabigh,
King Abdulaziz University, Jeddah, Saudi Arabia. A total of 438 young smokers
participated from the University and the general population. Data were collected
through anonymous, selfadministered questionnaires in the Arabic language that
contained questions about the reasons and motivations towards cigarette smoking
and barriers against quitting smoking. The questionnaire also contained several
questions regarding knowledge and attitude of the participants towards cigarette
smoking. The data was analyzed on SPSS16. RESULTS: The mean age of the
respondents was 22.9+/-3.48, out of 438 subjects 87 (19.9%) were married, and 351
(80.1%) were unmarried, and 331 (75.6%) belonged to urban areas while 107 (24.5%)
were from the rural areas. Responding to a question about a number of cigarettes
smoked per day, 31% answered 1120, 29% answered 2130, and 25% answered 110.
Questioned about smokers in the family, 34.5% responded more than one, with 19%
for brother and 13% for father. About the reasons for not quitting smoking, 26%
described lack of willpower, 25% had no reason, 22% said that people around me
smoke, and 15.3% responded stress at home/work. The major motivation for smokers
was smoker friends (42%), for 33.8% others, for 12% father/brother and 7.8%
media. CONCLUSIONS: There are several avoidable and preventable reasons and
barriers against quitting smoking. However, knowledge and attitude about smoking
were good, and the majority of the smokers were well aware of the associated
hazards. Therefore, there is a need to search out ways and means to help them to
quit this addiction.
PMID- 27509997
TI - SelfSampling Versus Physicians' Sampling for Cervical Cancer Screening Agreement
of Cytological Diagnoses.
AB - BACKGROUND: A major problem with cervical cancer screening in countries which
have no organized national screening program for cervical cancer is suboptimal
participation. Implementation of selfsampling method may increase the coverage.
OBJECTIVE: We determined the agreement of cytological diagnoses made on samples
collected by women themselves (selfsampling) versus samples collected by
physicians (Physician sampling). MATERIALS AND METHODS: We invited women
volunteers to undergo two procedures; cervical selfsampling using the Evalyn
brush and physician sampling using a Cervex brush. The women were shown a video
presentation on how to take their own cervical samples before the procedure. The
samples taken by physicians were taken as per routine testing (Gold Standard).
All samples were subjected to Thin Prep monolayer smears. The diagnoses made were
according to the Bethesda classification. The results from these two sampling
methods were analysed and compared. RESULTS: A total of 367 women were recruited
into the study, ranging from 22 to 65 years age. There was a significant good
agreement of the cytological diagnoses made on the samples from the two sampling
methods with the Kappa value of 0.568 (p=0.040). Using the cytological smears
taken by physicians as the gold standard, the sensitivity of selfsampling was
71.9% (95% CI:70.972.8), the specificity was 86.6% (95% CI:85.7 87.5), the
positive predictive value was 74.2% (95% CI:73.375.1) and the negative predictive
value was 85.1% (95% CI: 84.286.0). Selfsampling smears (22.9%) allowed detection
of microorganisms better than physicians samples (18.5%). CONCLUSIONS: This study
shows that samples taken by women themselves (selfsampling) and physicians have
good diagnostic agreement. Selfsampling could be the method of choice in
countries in which the coverage of women attending clinics for screening for
cervical cancer is poor.
PMID- 27509998
TI - Maximum Diameter of Intracranial Metastatic Lesions as a Prognostic Factor in
Patients Following Whole Brain Radiotherapy.
AB - PURPOSE: To evaluate whetehr maximum diameter of intracranial metastatic lesions
may be a prognostic factor in intracranial metastatic patients receiving whole
brain radiotherapy. MATERIALS AND METHODS: The records of 114 cases who between
January 2005 and December 2007 were retrospectively reviewed. There were 85 who
met the inclusion criteria. RESULTS: In these 85, the oneyear overall survival
rate was 16.5% and the median survival time was 125 days. Median survival in
relation to recursive partitioning analysis (RPA) classes I, II and III were 216,
133 and 85 days. Logrank tests of initial prognostic factors were significant for
RPA classifications, Karnofsky Performance Status(KPS), maximum diameters of
intracranial metastatic lesions and presence of necrotic centers. The median
survivals with a maximum diameter of the largest intracranial metastatic lesion
<3cm and >=3cm were 162 days and 104 days (p=0.027). Multivariate analysis also
showed a statistical significance for maximum diameter of intracranial metastatic
lesions and presence of necrotic centers. CONCLUSIONS: Maximum diameters of
intracranial metastatic lesions could be used as a prognostic factor in patients
receiving whole brain radiotherapy and may help radiation oncologists to make
decisions on treatment plans.
PMID- 27509999
TI - Lack of an Apparent Association between Mycotoxin Concentrations in Red Chili
Peppers and Incidence of Gallbladder Cancer in India : an Ecological Study.
AB - Our recent studies conducted in South America have shown that mycotoxin
contamination of red chili peppers (RCPs) may be associated with an increased
risk of gallbladder cancer (GBC). Whether this relationship exists in India, a
country with a high incidence of GBC and high consumption of RCPs, is unclear. We
therefore measured concentrations of aflatoxins (AFs) and ochratoxin A (OTA) in
RCPs from areas of low, medium, and high incidence of GBC in India, and compared
these concentrations with GBC incidence in each area. Twentyone RCP samples were
collected from nine cities (eight from a lowincidence area, five from a
mediumincidence area, and eight from a highincidence area). Concentrations of AFs
and OTA were measured using highperformance liquid chromatography. No significant
differences in mean concentrations of AFs and OTA were found in the three areas.
AFB1 levels in the lowincidence area (10.81 ?g/kg) and highincidence area (12.00
?g/kg) were more than 2.2 and 2.4 times higher compared with the maximum
permitted level of AFB1 in spices (5.0 ?g/kg) set by the Commission of the
European Communities, or that (4.4 ?g/kg) obtained in our previous study in
Chile. Our results show that the mean concentrations of mycotoxins in RCPs are
similar among the three areas in India with different incidences of GBC. Further
studies with human subjects are needed to evaluate any association between AFB1
and GBC.
PMID- 27510000
TI - Effects of Application of Social Marketing Theory and the Health Belief Model in
Promoting Cervical Cancer Screening among Targeted Women in Sisaket Province,
Thailand.
AB - Cervical cancer is a major public health problem in Thailand, being ranked second
only to breast cancer. Thai women have been reported to have a low rate of
cervical cancer screening (27.7% of the 80% goal of WHO). We therefore aimed to
apply the social marketing theory and health belief model in promoting cervical
cancer screening in Kanthararom District, Sisaket Province. A total of 92 from
974 targeted women aged 3060 years were randomly divided into two groups. The
experimental group underwent application of social marketing theory and a health
belief model program promoting cervical cancer screening while the control group
received normal services. Two research tools were used: (1) application of social
marketing theory and health belief model program and (2) questionnaire used to
evaluate perceptions of cervical cancer. Descriptive and inferential statistics
including paired sample ttest and independent ttest were used to analyze the
data. After the program had been used, the mean score of perception of cervical
cancer of experimental group was at a higher level (x=4.09; S.D. =0.30), than in
the control group (x=3.82; S.D. =0.20) with statistical significance (p<0.001).
This research demonstrated an appropriate communication process in behavioral
modification to prevent cervical cancer. It can be recommended that this program
featuring social marketing and the health belief model be used to promote
cervical cancer screening in targeted women and it can be promoted as a guideline
for other health services, especially in health promotion and disease prevention.
PMID- 27510001
TI - Outcomes of Preoperative Chemoradiotherapy and Combined Chemotherapy with
Radiotherapy Without Surgery for Locally Advanced Rectal Cancer.
AB - PURPOSE: To evaluate the treatment outcomes of patients with locally advanced
rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT) or
combined chemotherapy together with radiotherapy (CMTRT) without surgery.
MATERIALS AND METHODS: A total of 84 patients with locally advanced rectal
adenocarcinoma (stage II or III) between January 1st, 2003 and December 31st,
2013 were enrolled, 48 treated with preoperative CCRT (Gr.I) and 36 with combined
chemotherapy and radiotherapy (CMTRT) without surgery (Gr.II). The
chemotherapeutic agents used concurrent with radiotherapy were either
5fluorouracil short infusion plus leucovorin and/or capecitabine or 5fluorouracil
infusion alone. All patients received pelvic irradiation. RESULTS: There were 5
patients (10.4%) with a complete pathological response. The 3 yearoverall
survival rates were 83.2% in Gr.I and 24.8 % in Gr.II (p<0.01). The respective 5
yearoverall survival rates were 70.3% and 0% (p<0.01). The 5 yearoverall survival
rates in Gr.I for patients who received surgery within 56 days after complete
CCRT as compared to more than 56 days were 69.5% and 65.1% (p=0.91). Preoperative
CCRT used for 12 of 30 patients in Gr.I (40%) with lower rectal cancer
demonstrated that in preoperative CCRT a sphincter sparing procedure can be
performed. CONCLUSIONS: The results of treatment with preoperative CCRT for
locally advanced rectal cancer showed comparable rates of overall survival and
sphincter sparing procedures as compared to previous studies.
PMID- 27510002
TI - Trends in Survival of Childhood Cancers in a University Hospital, Northeast
Thailand, 19932012.
AB - BACKGROUND: In Thailand, a national treatment protocol for childhood leukemia and
lymphoma (LL) was implemented in 2006. Access to treatment has also improved with
the National Health Security system. Since these innovations, survival of
childhood LL has not been fully described. MATERIALS AND METHODS: Trends and
survival of children under 15 with childhood cancers diagnosed between 1993 and
2012 were investigated using the hospitalbased data from the Khon Kaen Cancer
Registry, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University,
Thailand. Childhood cancers were classified into 12 diagnostic groups, according
to the ICCC based on the histology of the cancer. Survival rates were described
by period, depending on the treatment protocol. For leukemias and lymphomas,
survival was assessed for 3 periods (199399, 20005, 200612) while for solid
tumors it was for 2 periods (before and after 2000). The impacts of sex, age, use
of the national protocol, and catchment area on leukemia and lymphoma were
evaluated. Overall survival was calculated using the KaplanMeier method while the
Cox proportional hazard model was used for multivariate analysis. Trends were
calculated using the R program. RESULTS: A total of 2,343 childhood cancer cases
were included. Survival for acute lymphoblastic leukemia (ALL) from 19939, 20005,
and 200612 improved significantly (43.7%, 64.6%, and 69.9%). This was to a lesser
extent true for acute nonlymphoblastic leukemia (ANLL) (28.1%, 42.0%, and 42.2%).
Survival of nonHodgkin lymphoma (NHL) also improved significantly (44%, 65.5%,
and 86.8%) but not for Hodgkin disease (HD) (30.1%, 66.1%, and 70.6%). According
to multivariate analysis, significant risk factors associated with poor survival
in the ALL group were age under 1 and over 10 years, while not using the national
protocol had hazard ratios (HR) of 1.6, 1.3, and 2.3 respectively. In NHL, only
nonuse of national protocols was a risk factor (HR 3.9). In ANLL and HD, none of
the factors influenced survival. Survival of solid tumors (liver tumors,
retinoblastomas) were significantly increased compared to after and before 2000
while survival for CNS tumors, neuroblastoma and bone tumors was not changed.
CONCLUSIONS: The survival of childhood cancer in Thailand has markedly improved.
Since implementation of national protocols, this is particularly the case for ALL
and NHL. These results may be generalizable for the whole country.
PMID- 27510003
TI - Digital Breast Tomosynthesis in Addition to Conventional 2DMammography Reduces
Recall Rates and is CostEffective.
AB - Digital breast tomosynthesis (DBT) as a breast cancer screening modality, through
generation of three dimensional images during standard mammographic compression,
can reduce interference from breast tissue overlap, increasing conspicuity of
invasive cancers while concomitantly reducing falsepositive results. We here
conducted a systematic review on previous studies to synthesize the evidence of
DBT efficacy, eventually 18 articles being included in the analysis. The most
commonly emerging topics were advantages of DBT screening tool in terms of recall
rates, cancer detection rates and costeffectiveness, preventing unnecessary
burdens on women and the healthcare system. Further research is needed to
evaluate the potential impact of DBT on longerterm outcomes, such as interval
cancer rates and mortality, to better understand the broader clinical and
economic implications of its adoption.
PMID- 27510004
TI - Lack of Effects of Recombinant Human Bone Morphogenetic Protein2 on Angiogenesis
in Oral Squamous Cell Carcinoma Induced in the Syrian hamster Cheek Pouch.
AB - Recombinant human bone morphogenetic protein2 (rhBMP2 ), a member of the TGF?
family, has been used widely in recent years to regenerate defects of the
maxillary and mandible bones. Such defects are sometimes caused by resection of
oral squamous cell carcinoma (OSCC) yet the biologic effects of rhBMP2 on these
carcinomas are not fully clear. The objective of this study was to determine
histologically whether rhBMP2 produces adverse effects on angiogenesis during
induction of OSCC, a biologic process critical for tumor formation in an
experimental model in the buccal pouch of golden Syrian hamsters. Buccal cavities
were exposed to painting with 0.5% DMBA in liquid paraffin three times a week for
14 weeks, then biopsies were taken. Division was into 2 groups: a study group of
10 hamsters receiving 0.25?g/ml of rhBMP2 in the 3rd and 6th weeks; and a control
group of 10 hamsters which did not receive any additional treatment. VEGF
expression and microvessel density were measured but no differences were noted
between the two groups. According to this study, rhBMP2 does not stimulate
angiogenesis during induction of OCSSs.
PMID- 27510005
TI - Smoking Initiation and Continuation A Qualitative Study among Bruneian Male
Adolescents.
AB - BACKGROUND: Cigarette smoking is one of the leading global causes of premature
and preventable death. In Brunei Darussalam, smokingrelated diseases have been a
primary cause of mortality for the past three decades. Despite the increasing
efforts that have been made in recent years to reduce the consumption of tobacco
products in Brunei, the prevalence of adolescent smoking cigarette, however has
risen alarmingly, from 8.9% in 2013 to 11.4% in 2014, with a higher prevalence
found in males (17.8%) than in females (4.8%). In response to the need for more
effective smoking prevention programmes in Brunei, this study sought to explore
factors that influence Bruneian male adolescents to start and continue smoking.
MATERIALS AND METHODS: A qualitative study using focus group discussions (FGDs)
as the data collection method was conducted from October to November 2015. A
total of 43 studentss, comprising 31 smokers and 12 nonsmokers, aged 1317 years,
from two government secondary schools in Bandar Seri Begawan, participated in six
FGDs. Discussions were recorded and translated. Transcripts were entered into
NVivo10, before thematic analysis was conducted. RESULTS: We identified three
themes under the core construct of 'factors influencing smoking initiation'
('family as teachers', 'overt pressure from peers' and 'perceived smoking has
many advantages') and three themes under the core construct of 'factors
influencing smoking continuation' ('craving and addiction', 'smoking as a 'social
activity' and 'easy accessibility of cigarettes'). CONCLUSIONS: Based on the
findings, it is recommended that future prevention activities should be embedded
in a comprehensive approach, involving all stakeholders within a community, and
should be focused towards bringing a change in smoking and parenting behavior of
parents, social norms within the culture towards all population levels, and at
strengthening the existing nonsmoking policies in schools and other public places
where young people congregate.
PMID- 27510006
TI - Comparing Survival of Oral Cancer Patients Before and After Launching of the
Universal Coverage Scheme in Thailand.
AB - BACKGROUND: As the treatment modalities for oral cancer have been relatively
consistent during the last two decades, this study was conducted to compare
survivals of oral cancer patients in Khon Kaen Province before and after the
universal coverage scheme (UC) was launched in Thailand. MATERIALS AND METHODS:
The data were retrieved from the populationbased cancer registry of Khon Kaen for
oral cancer patients diagnosed during 19922001 (preUC), and 20042012 (postUC). To
compare survival of the two cohorts, Kaplan Meier and log rank tests were
employed. RESULTS: Of 1,196 patients, 65% were females and the median age was 65
years. The most common primary sites were lip (31.0%), tongue (29.9%), and buccal
mucosa (14.6%). The proportion of early stage cancer increased from 20.4 % in
preUC to 41.3% in postUC. The overall 5year survival rate was 36.5% (95% CI
=32.640.9) for preUC and 32.4% (95% CI = 28.836.4) for postUC. The declining
survival was mainly due to an increasing proportion of tongue cancer. However, no
survival improvement was demonstrated on subgroup analysis of the tongue cancer
patients. CONCLUSIONS: After the universal coverage scheme had been launched,
early diagnosis increased, but no significant gain in survival for oral cancer
patients was achieved.
PMID- 27510007
TI - Risk Factors for Upper and Lower Urinary Tract Cancer Death in a Japanese
Population: Findings from the Japan Collaborative Cohort Study for Evaluation of
Cancer Risk (JACC Study).
AB - BACKGROUND: The incidence of bladder cancer is lower in Asian than in Western
countries. However, the crude incidence and mortality of bladder cancer have
recently increased in Japan because of the increased number of senior citizens.
We have already reported risk factors for urothelial cancer in a large
populationbased cohort study in Japan (JACC study). However, we did not evaluate
the cancer risk in the upper and lower urinary tract separately in our previous
study. MATERIALS AND METHODS: Here we evaluated the risk of cancer death in the
upper and lower urinary tracts, separately, using the database of the JACC study.
The analytic cohort included 46,395 males and 64,190 females aged 40 to 79 years
old. The Cox proportional hazard model was used to determine hazard ratios and
their 95% confidence intervals. RESULTS: Current smoking increased the risk of
both upper and lower urinary tract cancer deaths. A history of kidney disease was
associated with an increased risk of bladder cancer death, even after controlling
for age, sex and smoking status. CONCLUSIONS: The present study confirmed that
current smoking increases the risk of both upper and lower urinary tract cancer
deaths and indicated the possibility that a history of kidney disease may be a
risk factor for bladder cancer death in the Japanese population.
PMID- 27510008
TI - Unpolished Thai Rice Prevents Aberrant Crypt Foci Formation through the
Invovement of ?catenin and COX2 Expression in AzoxymethaneTreated Rats.
AB - Colorectal cancer (CRC) is a major cause of morbidity and mortality throughout
the world, with chronic inflammation and diet as major causes in its development.
Chemopreventive effects of natural dietary products have been the focus of
studies for prevention over the past decade. This study was conducted to
determine the effects of unpolished Thai rice during precancerous stage through
the involvement of ?catenin, cyclooxygenase2 (COX2) expression and inflammatory
cytokines focusing on azoxymethane (AOM)induced aberrant crypt foci (ACF)related
to CRC. Male Sprague Dawley rats received two injections of AOM (15 mg/kg body
weight) at weeks 4 and 5 while rats were treated with 20% or 70% unpolished Thai
rice. The rats were sacrificed at week 38 and the colons removed for aberrant
crypt foci (ACF) identification. Histopathologic changes, immunohistochemical
analysis of ?catenin and COX2 expression, and cytokine expression of
proinflammatory and antiinflammatory markers were determined. The administration
of unpolished Thai rice significantly and dose dependently decreased the total
number of ACF and the percentages of ACF with highgrade dysplasia. Interestingly,
unpolished Thai rice suppressed the expression of betacatenin and COX2. In
addition, it also altered proinflammatory (IL6 and IFNgamma) and antiinflammatory
(IL 10) markers. The results suggested that unpolished Thai rice may provide a
promising dietary intake for prevention during precancerous stage of CRC
development, through the involvement of betacatenin and COX2 expression, and also
modulate inflammatory cytokinesrelated to CRC.
PMID- 27510009
TI - In Vitro Studies on Phytochemical Content, Antioxidant, Anticancer,
Immunomodulatory, and Antigenotoxic Activities of Lemon, Grapefruit, and Mandarin
Citrus Peels.
AB - BACKGROUND: In recent years, there has been considerable research on recycling of
agroindustrial waste for production of bioactive compounds. The food processing
industry produces large amounts of citrus peels that may be an inexpensive source
of useful agents. OBJECTIVE: The present work aimed to explore the phytochemical
content, antioxidant, anticancer, antiproliferation, and antigenotxic activities
of lemon, grapefruit, and mandarin peels. MATERIALS AND METHODS: Peels were
extracted using 98% ethanol and the three crude extracts were assessed for their
total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant
activity using DPPH (1, 1diphenyl2picrylhydrazyl). Their cytotoxic and mitogenic
proliferation activities were also studied in human leukemia HL60 cells and mouse
splenocytes by CCK8 assay. In addition, genotoxic/ antigenotoxic activity was
explored in mouse splenocytes using chromosomal aberrations (CAs) assay. RESULTS:
Lemon peels had the highest of TPC followed by grapefruit and mandarin. In
contrast, mandarin peels contained the highest of TFC followed by lemon and
grapefruit peels. Among the extracts, lemon peel possessed the strongest
antioxidant activity as indicated by the highest DPPH radical scavenging, the
lowest effective concentration 50% (EC50= 42.97 ?g extract/ mL), and the highest
Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited
moderate cytotoxic activity (IC50 = 77.8 ?g/mL) against HL60 cells, whereas
grapefruit and lemon peels were ineffective antileukemia. Further, citrus peels
possessed immunostimulation activity via augmentation of proliferation of mouse
splenocytes (Tlymphocytes). Citrus extracts exerted noncytotoxic, and
antigenotoxic activities through remarkable reduction of CAs induced by cisplatin
in mouse splenocytes for 24 h. CONCLUSIONS: The phytochemical constituents of the
citrus peels may exert biological activities including anticancer,
immunostimulation and antigenotoxic potential.
PMID- 27510010
TI - Diagnosis of Hepatocellular Carcinoma Using C11 Choline PET/CT: Comparison with
F18 FDG, ContrastEnhanced MRI and MDCT.
AB - PURPOSE: The aim of this study was to compare C11 choline and F18 FDG PET/CT,
gadoxeticenhanced 3T MRI and contrastenhanced CT for diagnosis of hepatocellular
carcinoma (HCC). MATERIALS AND METHODS: Twelve chronic hepatitis B patients
suspected of having HCC by abdominal ultrasonography received all diagnostic
modalities performed within a oneweek timeslot. PET/CT results were analyzed
visually by two independent nuclear medicine physicians and quantitatively by
tumor to background ratio (T/B). Nine patients then had histopathological
confirmation. RESULTS: Six patients had well differentiated HCC, while two and
one patient(s) were noted with moderately and poorly differentiated HCC,
respectively. All were detected by both CT and MRI with an average tumor size of
5.7+/-3.8 cm. Five patients had positive C11 choline and F18 FDG uptake. Of the
remaining four patients, three with well differentiated HCC showed negative FFDG
uptake (one of which showed negative results by both tracers) and one patient
with moderately differentiated HCC demonstrated no C11 choline uptake despite
intense F18 FDG avidity. The overall HCC detection rates with C11 choline and F18
FDG were 78% and 67%, respectively, while the sensitivity of F18 FDG for nonwell
differentiated HCC was 100%, compared with 83% of C11 choline. The average T/B of
C11 choline in welldifferentiated HCC patients was higher than in moderately and
poorly differentiated cases (p=0.5) and vice versa with statistical significance
for T/B of F18 FDG (p = 0.02). CONCLUSIONS: Our results suggested better
detection rate in C11 choline for well differentiated HCC than F18 FDG PET.
However, the overall detection rate of PET/CT with both tracers could not compare
with contrastenhanced CT and MRI.
PMID- 27510011
TI - Survival Analysis and Prognostic Factors for Colorectal Cancer Patients in
Malaysia.
AB - BACKGROUND: Cancer survival analysis is an essential indicator for effective
early detection and improvements in cancer treatment. This study was undertaken
to document colorectal cancer survival and associated prognostic factors in
Malaysians. MATERIALS AND METHODS: All data were retrieved from the National
Cancer Patient Registry Colorectal Cancer. Only cases with confirmed diagnosis
through histology between the year 2008 and 2009 were included. Retrieved data
include sociodemographic information, pathological features and treatment
received. Survival curves were plotted using the KaplanMeier method. Univariate
analysis of all variables was then made using the Logrank test. All significant
factors that influenced survival of patients were further analysed in a
multivariate analysis using Cox' regression. RESULTS: Total of 1,214 patients
were included in the study. The overall 3 and 5year survival rates were 59.1% and
48.7%, respectively. Patients with localized tumours had better prognosis
compared to those with advanced stage cancer. In univariate analysis, staging at
diagnosis (p<0.001), primary tumour size (p<0.001), involvement of lymph nodes
(p<0.001) and treatment modalities (p=0.001) were found to be predictors of
survival. None of the sociodemographic characteristics were found to exert any
influence. In Cox regression analysis, staging at diagnosis (p<0.001), primary
tumour size (p<0.001), involvement of lymph nodes (p<0.001) and treatment
modalities (p<0.001) were determined as independent prognostic factors of
survival after adjusted for age, gender and ethnicity. CONCLUSIONS: The overall
survival rate for colorectal cancer patients in Malaysia is similar to those in
other Asian countries, with staging at diagnosis, primary tumor size, involvement
of lymph node and treatment modalities having significant effects. More efforts
are needed to improve national survival rates in future.
PMID- 27510012
TI - Investigating Sexual Function and Affecting Factors in Women with Breast Cancer
in Iran.
AB - BACKGROUND: Since the breast is strongly relevant to sexual desire, and physical
and sexual attractiveness, the high prevalence of breast cancer (BC) in Iran and
longterm survival of patients experiencing side effects means that measures to
identify associated sexual problems are necessary. Therefore, this study was
conducted to assess sexual function and affecting factors in women with BC.
MATERIALS AND METHODS: This crosssectional study was performed on 94 women with
BC, referred to Imam Reza (AS) Hospital, Mashhad, Iran, in 2014. The data were
collected through demographic and clinical questionnaires and also a sexual
function questionnaire and analyzed using SPSS version 16. RESULTS: The total
score of women's sexual function was about 24.3+/-4.41. Of the total, 63 (71.3%)
reported sexual dysfunction, for example reduced satisfaction or more pain. Age
was the only significantly related factor. CONCLUSIONS: Breast cancer can
adversely affect women's sexual function and decrease quality of life. Thus,
taking measures to overcome women's sexual problems are necessary.
PMID- 27510013
TI - Risk Factors for Breast Cancer in Postmenopausal Women in Brazil.
AB - PURPOSE: To analyze risk factors for postmenopausal breast cancer. METHODS: The
present casecontrol study included 600 women treated at a cancer center reference
hospital in a municipality in the South of Brazil. RESULTS: Totals of 100
patients and 500 control subjects were evaluated. The mean age of the women was
52.5 +/- 11.9 years; the average was 57.4 +/- 11.8 years, and the average age of
the control subjects was 51.5 +/- 11.7 years. The risk factors for breast cancer
that were considered included an age >= 40 years, postmenopausal status, a body
mass index (BMI) >= 30 kg/m2, and reduced physical activity. Variables like
postmenopausal status and an obese BMI were associated with cases of breast
cancer. Women who were postmenopausal or obese were 3.80 or 1.80 times more
likely to develop breast cancer, respectively, and physically inactive women were
1.72 times more likely to develop breast cancer. CONCLUSIONS: Obesity and
postmenopausal status are associated with the occurrence of breast cancer in this
population. Being over 40 years of age was also a statistically significant
factor for postmenopausal women.
PMID- 27510014
TI - Correlation of Preoperative Ki67 and Serum CA15.3 Levels with Outcome in Early
Breast Cancers a Multi Institutional Study.
AB - BACKGROUND: To investigate the association between preoperative pathological Ki67
labeling index and serum tumor marker cancer antigen 153 (CA 153) with
clinicpathological parameters and treatment outcomes in early breast cancer.
MATERIALS AND METHODS: A retrospective study at 4 cancer centers in Saudi Arabia
and Egypt was performed. Data were collected for female patients diagnosed with
unilateral early breast cancer between March 2010 and October 2013. Cases treated
with neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy were
included. NACT included 68 cycles of anthracycline and taxane based regimens.
Trastuzumab and hormonal treatments were added according to HER2 and hormone
receptor status. Baseline serum CA15.3 and pathological Ki67 levels were
evaluated and correlated with disease free survival (DFS) and overall survival
(OS). RESULTS: A total of 280 pts was included. The median age was 49 years (3866
y) and median overall survival was 35 (2038) months (mo). Estrogen receptors
(ER), progesterone receptors (PR) and HER 2 receptors were positive in 233
(83.2%), 198 (70%) and 65 cases (23.2%), respectively. High preoperative Ki67 and
CA15.3 were noted in 177 (63.2%) and 131 (46.8%). A total of 45 (16%) patients
had distal or local recurrence and 24 (8.6%) died of their disease. Most of the
relapsed cases had high preoperative Ki67 (n=41, 91%) and CA15.3 (n=28, 62%)
values. All of the patients who died had a high Ki67 but CA15.3 was high in 9
(37%) only. Mean DFS/OS in patients with high preoperative Ki67 was 32 months /32
months as compared to 37 months/35 months in those with normal Ki67 (p<0.001).
Correlation of preoperative CA15.3 and survival was statistically not
significant. CONCLUSIONS: Preoperative Ki67 can be a predictive and prognostic
marker. Higher levels are associated with poor DFS and OS in patients with early
BC.
PMID- 27510015
TI - Decreased Serum Monocyte Chemoattractant Protein1 in Salivary Gland Tumor
Patients.
AB - BACKGROUND: The monocyte chemoattractant protein1 (MCP1/CCL2) is a potent
chemoattractant for natural killer cells, monocytes, and memory T lymphocytes.
However, any role in the genesis of salivary gland tumors (SGT) is unknown. To
assess the diagnostic relevance of chemokines in SGT, MCP1 levels in the serum of
patients were investigated in association with tumor progression and clinical
aggressiveness. MATERIALS AND METHODS: Using an ELISA kit, we assessed and
compared the circulating levels of MCP1 in blood serum of 70 SGT patients with 44
healthy control samples. RESULTS: The results of this study showed that the
concentration of MCP1 was significantly lower in patients with benign (463.8+/
158.5pg/ml, P=0.033) and malignant (454.8+/-190.4pg/ ml, P=0.007) SGT than in
healthy subjects (645.7+/-338.9). No significant difference in mean serum levels
of MCP1 was observed between the benign and malignant group (p=0.9). While MCP1
levels were lower in patients with an advanced clinical stage, advanced tumor
size, higher tumor grade, or lymph node involvement, but the mean MCP1 level
between groups showed no statistically significant difference (p>0.05).
CONCLUSIONS: MCP1 levels in the serum of patients with SGT were decreased,
indicating that this might a good marker for discriminating patients with SGT
from healthy people. However, no clearcut relationship was detected between MCP1
levels and clinicopathologic factors, and MCP1 is not a good marker for
evaluating tumor dissemination.
PMID- 27510016
TI - Comparison of Expression Signature of Histone Deacetylases (HDACs) in Mesenchymal
Stem Cells from Multiple Myeloma and Normal Donors.
AB - BACKGROUND: Histone acetylation in chromatin structures plays a key role in
regulation of gene transcription and is strictly controlled by histone
acetyltransferase (HAT) and deacetylase (HDAC) activities. HDAC deregulation has
been reported in several cancers. MATERIALS AND METHODS: The expression of 10
HDACs (including HDAC class I and II) was studied by quantitative reverse
transcriptionPCR (qRTPCR) in a cohort of mesenchymal stem cells (MMMSCs) from 10
multiple myeloma patients with a median age 60y. The results were compared with
those obtained for normal donors. Then, a coculture system was performed between
MMMSCs and u266 cell line, in the presence or absence of sodium butyrate (NaBT),
to understand the effects of HDAC inhibitors (HDACi) in MMMSCs on multiple
myeloma cases. Also, the interleukin6 (IL6) and vascular endothelial growth
factor (VEGFA) gene expression level and apoptotic effects were investigated in
MMMSCs patients and control group following NaBT treatment. RESULTS: The results
indicated that upregulated (HDACs) and downregulated (IL6 and VEGFA) genes were
differentially expressed in the MMMSCs derived from patients with multiple
myeloma and NDMSCs from normal donors. Comparison of the MMMSCs and NDMSCs also
showed distinct HDACs expression patterns. For the first time to our knowledge, a
significant increase of apoptosis was observed in coculture with MMMSCs treated
with NaBT. CONCLUSIONS: The obtained findings elucidate a complex set of actions
in MSCs in response to HDAC inhibitors, which may be responsible for anticancer
effects. Also, the data support the idea that MSCs are new therapeutic targets as
a potential effective strategy for MM.
PMID- 27510017
TI - Randomized DoubleBlind PlaceboControlled Trial of Propolis for Oral Mucositis in
Patients Receiving Chemotherapy for Head and Neck Cancer.
AB - BACKGROUND: Propolis based preparations have a wide range of applications in
various specialties of dentistry. The aim of this clinical trial was to test the
efficacy of propolis as a mouthwash in the reduction of chemotherapy induced oral
mucositis (OM) in a single center. MATERIALS AND METHODS: In this randomised,
controlled study patients undergoing chemotherapy were included consecutively and
randomised to an experimental group receiving propolis mouthwash (n = 20) and a
control group receiving diluted water (n=20). Oral mucositis, erythema and eating
and drink ability were assessed at baseline and after 3 and 7 days using the
World Health Organization (WHO) scale and the oral mucositis assessment scale
(OMAS). RESULTS: There were significant differences in OM, wound and erythema in
propolis group compared to placebo, but no significant difference in eating and
drink ability. However, it was interesting that 65% of the patients in the
propolis group were completely healed at day 7 of the trial. No significant
adverse events were reported by the patients. CONCLUSIONS: This study found that
oral care with propolis as mouthwash for patients undergoing chemotherapy is an
effective intervention to improve oral health. Our findings shouldlencourage
health practitioners to apply propolis mouth rinse for the oral care of patients
under chemotherapy.
PMID- 27510018
TI - Haplotype Analysis of BRCA1 Gene D17S855 and D17S1322 Markers in Iranian Familial
Breast Cancer Patients.
AB - BACKGROUND: Breast cancer molecular analysis by linkage analysis has the
advantage of facilitating early diagnosis in asymptomatic genetic carriers, with
a view to the preventive followup of these subjects and genetic counseling. The
aim of this study was to evaluate BRCA1 gene D17S855 and D17S1322 markers in
breast cancer patients. MATERIALS AND METHODS: A series of 107 BC patients and 93
unrelated healthy women were recruited for haplotype analysis performed using two
short tandem repeat markers located within the BRCA1 gene locus. Each marker was
amplified with PCR genomic DNA from each individual and fluorescently endlabeled
primers. RESULTS: Both D17S855 and D17S1322 markers included 12 kinds of alleles.
Results indicate that most of the BC patients shared two common 121150 (11.2%,
RR=1.56 and p=0.02) and 121146 (5.6%, RR=1.9 and p=0.02) haplotypes. CONCLUSIONS:
Our results should be helpful to understand the haplotype phase in the BRCA1 gene
and establish a genetic screening strategy in the Iranian population.
PMID- 27510019
TI - Immunohistochemical Expression of B Cell Lymphoma2 with Clinicopathological
Correlation in Triple Negative Breast Cancers in Northern Pakistan.
AB - BACKGROUND: Triple negative breast cancers (TNBCs) are high grade aggressive
tumors generally with a poor prognosis, not responding to hormonal and anti Her2
Neu therapy. Expression of the antiapoptotic B cell lymphoma 2 gene (Bcl2) is
associated with low grade, slowly proliferating hormone receptor positive tumors
with improved survival. Anti Bcl2 agents can be used as alternative targeted
therapy in triple negative cancers. MATERIALS AND METHODS: The objective of this
study was to determine the immunohistochemical expression of Bcl2 in triple
negative breast cancers and any correlation with clinicopathological variables in
Northern Pakistan. RESULTS: All 52 patients were females, aged between 28 and 80
years(average 48.0+/-12.1). 28 cases (53.8%) were positive for Bcl2, this being
associated with low grade invasive ductal carcinomas, lymph node metastasis and
lymphovascular invasion. CONCLUSIONS: Bcl2 may be an important prognostic factor
and its expression might be used for targeted therapy using Anti Bcl2 drugs.
PMID- 27510020
TI - Novel Nonsense Variants c.58C>T (p.Q20X) and c.256G>T (p.E85X) in the CHEK2 Gene
Identified in Breast Cancer Patients from Balochistan.
AB - Breast cancer is very common and the leading cause of cancer deaths among women
globally. Hereditary cases account for 510% of the total burden and CHEK2, which
plays crucial role in response to DNA damage to promote cell cycle arrest and
repair or induce apoptosis, is considered as a moderate penetrance breast cancer
risk gene. Our objective in the current study was to analyze mutations in related
to breast cancer. A total of 271 individuals including breast cancer patients and
normal subjects were enrolled and all 14 exons of CHEK2 were amplified and
sequenced. The majority of the patients (>95%) were affected with invasive ductal
carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5%
with advanced stages III and IV. Two novel nonsense variants i.e. c.58C>T
(P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were
identified, both novel and not reported elsewhere.
PMID- 27510021
TI - A Novel Mutation in the DNA Binding Domain of NFKB is Associated with Speckled
Leukoplakia.
AB - BACKGROUND: Activation and inactivation of nuclear factor of kappa light chain
gene enhancer in B cells (NFKB) is tightly regulated to ensure effective onset
and cessation of defensive inflammatory signaling. However, mutations within
NFKB, or change in activation and inactivation molecules have been reported in a
few cancers. Although oral squamous cell carcinoma is one of the most prevalent
forms of cancer in India, with a development associated with malignant
transformation of precancerous lesions, the genetic status of NFKB and relative
rates of change in oral precancerous lesions remain unknown. Hence in the present
study we investigated all twenty four exons of NFKB gene in two precancerous
lesions, namely oral submucous fibrosis (OSMF) and oral leukoplakia (OL) to
understand its occurrence, incidence and assess its possible contribution to
malignant transformation. MATERIALS AND METHODS: Chromosomal DNA isolated from
twenty five each of OSMF and OL tissue biopsy samples were subjected to PCR
amplification with intronic primers flanking twenty four exons of the NFKB gene.
The PCR amplicons were subsequently subjected to direct sequencing to elucidate
the mutation status. RESULTS: Sequence analysis identified a novel heterozygous
mutation, c.419T>A causing substitution of leucine with glutamine at codon 140
(L140Q) in an OL sample. CONCLUSIONS: The identification of a substitution
mutation L140Q within the DNA binding domain of NFKB in OL suggests that NFKB
mutation may be relatively an early event during transformation. To the best of
our knowledge, this study is the first to have identified a missense mutation in
NFKB in OL.
PMID- 27510022
TI - Breast Lymphoma Treatment Outcomes in a Pakistani Population: 20 Years of
Experience at a Single Center.
AB - BACKGROUND: Breast lymphomas constitute a rare disease entity. To date, limited
relevant data have been reported. We therefore here present a review of breast
lymphoma patients treated at a single center over a 20 year period, focusing on
histological types, treatment modalities and outcomes. MATERIALS AND METHODS: We
identified patients who were diagnosed and treated for breast lymphoma at a
single center from January 1995 to January 2014 and extracted data regarding
patient demographics and clinical data. RESULTS: Twenty-seven patients with
breast lymphoma were identified, of which 3 were males. The median age at
diagnosis was 37 years (range: 22-76 years). Chemotherapy was the main stay of
treatment and 55.6% patients also received radiation to the affected breast. At
our institute, only 3 patients, all with progressive disease, had surgery
performed to achieve local palliation. Complete response after chemotherapy was
seen in 63% patients and partial response in 7.4%, while 26% patients
demonstrated disease progression. The mean follow up was 46.8 months. Seven
patients (33.3%) who were alive at last follow up, as well as 1 patient who died,
survived more than 5 years after diagnosis. CONCLUSIONS: Patients with breast
lymphoma should receive aggressive treatment, with combination of chemotherapy
and radiation therapy. Surgery should be limited for diagnosis and palliation of
local symptoms in cases of progressive disease.
PMID- 27510023
TI - Detection of Human Papillomavirus among Women with Atypical Squamous Cells of
Undetermined Significance Referred to Colposcopy: Implications for Clinical
Management in Low and MiddleIncome Countries.
AB - To determine the prevalence of human papillomavirus (HPV) among women with
atypical squamous cells of undetermined significance (ASC-US) referred to
colposcopy and the implications for clinical management in low- and middle-income
countries (LMIC), the present study was conducted. We included 200 women living
in Maringa/Brazil referred to colposcopy service between August 2012 and March
2013 due to an abnormal cytology from ASC-US until high-grade intraepithelial
lesion (HSIL). HPV was detected and genotyped by polymerase chain reaction (PCR).
The mean age was 36.8+/-10.5 years, and women with and without ASC-US had similar
mean ages (37.4+/-11.5 and 36.4+/-9.96 years, respectively). The highest
prevalence of ASC-US occurred at 20-24 years (40%). HPV-DNA was positive in 164
(82.0%) women.Of the 57 women with ASC-US, 30 (52.6%) were HPV-DNA-positive and
21 (70%) were high-risk HPV-positive (HR-HPV); the latter was similar to women
without ASC-US (76.9%) but with other abnormal cytological findings present. Our
data demonstrated that performing tests for HR-HPV can be used for management of
women with ASC-US to support the decision of which women should be referred for
an immediate or later colposcopy. The same conclusions can be applied to other
LMICs for which HPV testing for primary screening has not been adopted.
PMID- 27510024
TI - Radiation Therapy for Primary Eyelid Cancers in Tunisia.
AB - Management of eyelid cancers is based on surgery and/or radiotherapy (RT). The
treatment objective is to control tumors with acceptable functional and esthetic
outcomes. The aim of this study was to evaluate the results of radiation therapy
in management of epithelial eyelid cancers, reviewing retrospectively the
clinical records of patients treated in our institution from January 1989 to
December 2013. We focused on clinical and histological features, treatment
characteristics, tolerance and disease control. One hundred and eight patients
(62 men and 46 women) were enrolled, with a mean age of 61 years [ranges 1587].
The most frequent tumor location was the inner canthus (42.6%). Median tumor size
was 21 mm [ranges 470]. Histological type was basal cell carcinoma in 88 cases
(81.5%), squamous cell carcinoma in 16 (14.8%) and sebaceous carcinoma in 4
(3.7%). Radiation therapy was exclusive in 67 cases (62%) and postoperative for
positive or close margins in the remaining cases. Kilovoltage external beam
radiotherapy (KVRT) was used in 63 patients (58.3%) and lowdoserate interstitial
brachytherapy in 37 (34.3%). Eight (7.4%) were treated with cobalt or with a
combination of KVRTcobalt, KVRTelectron beams, KVRTbrachytherapy or
cobaltelectron beams. The total delivered radiation doses were 70 Gy (2
Gy/fraction) in 62 patients (57.4%), 66 Gy (2 Gy/fraction) in 37 (34.3%) and 61.2
Gy (3.4Gy/fraction) in 9 (8.3%). After a median followup of 64 months, we noted
10 cases of local recurrences(9.2%): 7 after exclusive and 3 after postoperative
RT. No local recurrence occurred in patients treated with brachytherapy.
Actuarial 5year local recurrencefree rate, diseasefree survival and overall
survival were respectively 90%, 90% and 97%. Tstage was found to be a significant
factor for recurrence (p=0.047). All acute radiationrelated reactions were scored
grade I or II. Delayed effects were eye watering in 24 cases (22.2%), eye dryness
in 19 (17.6%), unilateral cataract in 7 (6.4%) and ectropion in 4 (3.7%).
Radiation therapy and especially brachytherapy is an efficient treatment of
eyelid cancers, allowing eye conservation and functional preservation with good
local control rates and acceptable toxicity.
PMID- 27510025
TI - Colorectal Cancer in the Central Region of Thailand.
AB - BACKGROUND: Colorectal cancer is one of the major health problems worldwide.
However, limited studies have been reported from ASEAN countries. This study was
conducted to evaluate clinical characteristics and survival of colorectal cancer
cases aged <65 years and >=65 years in the central region of Thailand. MATERIALS
AND METHODS: Clinical information, histological features, endoscopic findings and
treatment outcome were collected and reviewed from Thammasat University Hospital,
Pathumthani, Thailand between November 2011 and October 2015. RESULTS: A total of
121 colorectal cancer patients, comprising 69 men and 52 women with a mean age of
65.8 years, were included. There were 57 aged <65 years and 64 aged >=65 years.
Common presenting symptoms were abdominal pain (37%), weight loss (34%) and
anemia (32%). Mean duration of symptoms prior to diagnosis was 173 days. However,
longer diagnosis time was demonstrated in patients aged <65 years than age more
than >=65 years (119.4 vs 58.4 days, Pvalue=0.30). Colonic fungating mass was the
most common endoscopic finding (64.4%) and the location was significantly more
commonly left than right side of the colon, both in younger and elderly groups
(87.7% vs 12.3%, P=0.02 and 70.3% vs 29.7%, P=0.02, respectively). Adenocarcinoma
with moderated differentiated was the most common histology (67.3%). More than
half of the patients presented with advanced stage (28.9% with TNM stage 3 and
38.8% TNM stage 4, respectively). Overall 1year and 5year survival rates were
76.9% and 5%. CONCLUSIONS: Most colorectal cancer patients in Thailand have
adenocarcinomas and present at advanced stage with poor prognosis. Screening of
high risk patients and early detection might be essential factors to improve the
treatment outcome and overall survival rate of colon cancer patients in Thailand
and other ASEAN countries.
PMID- 27510026
TI - Using a GeneticFuzzy Algorithm as a Computer Aided Breast Cancer Diagnostic Tool.
AB - Computeraided diagnosis of breast cancer is an important medical approach. In
this research paper, we focus on combining two major methodologies, namely fuzzy
base systems and the evolutionary genetic algorithms and on applying them to the
Saudi Arabian breast cancer diagnosis database, to aid physicians in obtaining an
earlycomputerized diagnosis and hence prevent the development of cancer through
identification and removal or treatment of premalignant abnormalities; early
detection can also improve survival and decrease mortality by detecting cancer at
an early stage when treatment is more effective. Our hybrid algorithm, the
geneticfuzzy algorithm, has produced optimized systems that attain high
classification performance, with simple and readily interpreted rules and with a
good degree of confidence.
PMID- 27510027
TI - Role of Accredited Social Health Activists in Cancer Screening in India:
Brightest 'Ray of Hope'.
PMID- 27510028
TI - History of Surgery is an Important Risk Factor for Breast Cancer.
PMID- 27510029
TI - Spray-Coated Multiwalled Carbon Nanotube Composite Electrodes for Thermal Energy
Scavenging Electrochemical Cells.
AB - Spray-coated multiwalled carbon nanotube/poly(vinylidene fluoride) (MWCNT/PVDF)
composite electrodes, scCNTs, with varying CNT compositions (2 to 70 wt %) are
presented for use in a simple thermal energy-scavenging cell (thermocell) based
on the ferro/ferricyanide redox couple. Their utility for direct thermal-to
electrical energy conversion is explored at various temperature differentials and
cell orientations. Performance is compared to that of buckypaper, a 100% CNT
sheet material used as a benchmark electrode in thermocell research. The 30 to 70
wt % scCNT composites give the highest power output by electrode area-seven times
greater than buckypaper at DeltaT = 50 degrees C. CNT utilization is drastically
enhanced in our electrodes, reaching 1 W gCNT(-1) compared to 0.036 W gCNT(-1)
for buckypaper. Superior performance of our spray-coated electrodes is attributed
to both wettability with better use of a large portion of electrochemically
active CNTs and minimization of ohmic and thermal contact resistances. Even
composites with as low as 2 wt % CNTs are still competitive with prior art. The
MWCNT/PVDF composites developed herein are inexpensive, scalable, and serve a
general need for CNT electrode optimization in next-generation devices.
PMID- 27510030
TI - Public stewardship of private for-profit healthcare providers in low- and middle
income countries.
AB - BACKGROUND: Governments use different approaches to ensure that private for
profit healthcare services meet certain quality standards. Such government
guidance, referred to as public stewardship, encompasses government policies,
regulatory mechanisms, and implementation strategies for ensuring accountability
in the delivery of services. However, the effectiveness of these strategies in
low- and middle-income countries (LMICs) have not been the subject of a
systematic review. OBJECTIVES: To assess the effects of public sector regulation,
training, or co-ordination of the private for-profit health sector in low- and
middle-income countries. SEARCH METHODS: For related systematic reviews, we
searched the Cochrane Database of Systematic Reviews (CDSR) 2015, Issue 4;
Database of Abstracts of Reviews of Effectiveness (DARE) 2015, Issue 1; Health
Technology Assessment Database (HTA) 2015, Issue 1; all part of The Cochrane
Library, and searched 28 April 2015. For primary studies, we searched MEDLINE,
Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Daily and
MEDLINE 1946 to Present, OvidSP (searched 16 June 2016); Science Citation Index
and Social Sciences Citation Index 1987 to present, and Emerging Sources Citation
Index 2015 to present, ISI Web of Science (searched 3 May 2016 for papers citing
included studies); Cochrane Central Register of Controlled Trials (CENTRAL),
2015, Issue 3, part of The Cochrane Library (including the Cochrane Effective
Practice and Organisation of Care (EPOC) Group Specialised Register) (searched 28
April 2015); Embase 1980 to 2015 Week 17, OvidSP (searched 28 April 2015); Global
Health 1973 to 2015 Week 16, OvidSP (searched 30 April 2015); WHOLIS, WHO
(searched 30 April 2015); Science Citation Index and Social Sciences Citation
Index 1975 to present, ISI Web of Science (searched 30 April 2015); Health
Management, ProQuest (searched 22 November 2013). In addition, in April 2016, we
searched the reference lists of relevant articles, WHO International Clinical
Trials Registry Platform, Clinicaltrials.gov, and various electronic databases of
grey literature. SELECTION CRITERIA: Randomised trials, non-randomised trials,
interrupted time series studies, or controlled before-after studies. DATA
COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and
extracted data, comparing their results and resolving discrepancies by consensus.
We expressed study results as risk ratios (RR) or mean differences (MD) with 95%
confidence intervals (CI), where appropriate, and assessed the certainty of the
evidence using Grades of Recommendation, Assessment, Development and Evaluation
(GRADE). We did not conduct meta-analysis because of heterogeneity of
interventions and study designs. MAIN RESULTS: We identified 20,177 records, 50
of them potentially eligible. We excluded 39 potentially eligible studies because
they did not involve a rigorous evaluation of training, regulation, or co
ordination of private for-profit healthcare providers in LMICs; five studies
identified after the review was submitted are awaiting assessment; and six
studies met our inclusion criteria. Two included studies assessed training alone;
one assessed regulation alone; three assessed a multifaceted intervention
involving training and regulation; and none assessed co-ordination. All six
included studies targeted private for-profit pharmacy workers in Africa and
Asia.Three studies found that training probably increases sale of oral
rehydration solution (one trial in Kenya, 106 pharmacies: RR 3.04, 95% CI 1.37 to
6.75; and one trial in Indonesia, 87 pharmacies: RR 1.41, 95% CI 1.03 to 1.93)
and dispensing of anti-malarial drugs (one trial in Kenya, 293 pharmacies: RR
8.76, 95% CI 0.94 to 81.81); moderate-certainty evidence.One study conducted in
the Lao People's Democratic Republic shows that regulation of the distribution
and sale of registered pharmaceutical products may improve composite pharmacy
indicators (one trial, 115 pharmacies: improvements in four of six pharmacy
indicators; low-certainty evidence).The outcome in three multifaceted
intervention studies was the quality of pharmacy practice; including the ability
to ask questions, give advice, and provide appropriate treatment. The trials
applied regulation, training, and peer influence in sequence; and the study
design does not permit separation of the effects of the different interventions.
Two trials conducted among 136 pharmacies in Vietnam found that the multifaceted
intervention may improve the quality of pharmacy practice; but the third study,
involving 146 pharmacies in Vietnam and Thailand, found that the intervention may
have little or no effects on the quality of pharmacy practice (low-certainty
evidence).Only two studies (both conducted in Vietnam) reported cost data, with
no rigorous assessment of the economic implications of implementing the
interventions in resource-constrained settings. No study reported data on equity,
mortality, morbidity, adverse effects, satisfaction, or attitudes. AUTHORS'
CONCLUSIONS: Training probably improves quality of care (i.e. adherence to
recommended practice), regulation may improve quality of care, and we are
uncertain about the effects of co-ordination on quality of private for-profit
healthcare services in LMICs. The likelihood that further research will find the
effect of training to be substantially different from the results of this review
is moderate; implying that monitoring of the impact is likely to be needed if
training is implemented. The low certainty of the evidence for regulation implies
that the likelihood of further research finding the effect of regulation to be
substantially different from the results of this review is high. Therefore, an
impact evaluation is warranted if government regulation of private for-profit
providers is implemented in LMICs. Rigorous evaluations of these interventions
should also assess other outcomes such as impacts on equity, cost implications,
mortality, morbidity, and adverse effects.
PMID- 27510031
TI - Probing Receptor Specificity by Sampling the Conformational Space of the Insulin
like Growth Factor II C-domain.
AB - Insulin and insulin-like growth factors I and II are closely related protein
hormones. Their distinct evolution has resulted in different yet overlapping
biological functions with insulin becoming a key regulator of metabolism, whereas
insulin-like growth factors (IGF)-I/II are major growth factors. Insulin and IGFs
cross-bind with different affinities to closely related insulin receptor isoforms
A and B (IR-A and IR-B) and insulin-like growth factor type I receptor (IGF-1R).
Identification of structural determinants in IGFs and insulin that trigger their
specific signaling pathways is of increasing importance in designing receptor
specific analogs with potential therapeutic applications. Here, we developed a
straightforward protocol for production of recombinant IGF-II and prepared six
IGF-II analogs with IGF-I-like mutations. All modified molecules exhibit
significantly reduced affinity toward IR-A, particularly the analogs with a Pro
Gln insertion in the C-domain. Moreover, one of the analogs has enhanced binding
affinity for IGF-1R due to a synergistic effect of the Pro-Gln insertion and S29N
point mutation. Consequently, this analog has almost a 10-fold higher IGF-1R/IR-A
binding specificity in comparison with native IGF-II. The established IGF-II
purification protocol allowed for cost-effective isotope labeling required for a
detailed NMR structural characterization of IGF-II analogs that revealed a link
between the altered binding behavior of selected analogs and conformational
rearrangement of their C-domains.
PMID- 27510032
TI - The Histamine H3 Receptor Differentially Modulates Mitogen-activated Protein
Kinase (MAPK) and Akt Signaling in Striatonigral and Striatopallidal Neurons.
AB - The basal ganglia have a central role in motor patterning, habits, motivated
behaviors, and cognition as well as in numerous neuropsychiatric disorders.
Receptors for histamine, especially the H3 receptor (H3R), are highly expressed
in the striatum, the primary input nucleus of the basal ganglia, but their
effects on this circuitry have been little explored. H3R interacts with dopamine
(DA) receptors ex vivo; the nature and functional importance of these
interactions in vivo remain obscure. We found H3R activation with the agonist R-(
)-alpha-methylhistamine to produce a unique time- and cell type-dependent profile
of molecular signaling events in the striatum. H3 agonist treatment did not
detectably alter extracellular DA levels or signaling through the cAMP/DARPP-32
signaling pathway in either D1- or D2-expressing striatal medium spiny neurons
(MSNs). In D1-MSNs, H3 agonist treatment transiently activated MAPK signaling and
phosphorylation of rpS6 and led to phosphorylation of GSK3beta-Ser9, a novel
effect. Consequences of H3 activation in D2-MSNs were completely different. MAPK
signaling was unchanged, and GSK3beta-Ser9 phosphorylation was reduced. At the
behavioral level, two H3 agonists had no significant effect on locomotion or
stereotypy, but they dramatically attenuated the locomotor activation produced by
the D1 agonist SKF82958. H3 agonist co-administration blocked the activation of
MAPK signaling and the phosphorylation of rpS6 produced by D1 activation in D1
MSNs, paralleling behavioral effects. In contrast, GSK3beta-Ser9 phosphorylation
was seen only after H3 agonist treatment, with no interactive effects. H3R
signaling has been neglected in models of basal ganglia function and has
implications for a range of pathophysiologies.
PMID- 27510033
TI - HCO3- Transport through Anoctamin/Transmembrane Protein ANO1/TMEM16A in
Pancreatic Acinar Cells Regulates Luminal pH.
AB - The identification of ANO1/TMEM16A as the likely calcium-dependent chloride
channel of exocrine glands has led to a more detailed understanding of its
biophysical properties. This includes a calcium-dependent change in channel
selectivity and evidence that HCO3 (-) permeability can be significant. Here we
use freshly isolated pancreatic acini that preserve the luminal structure to
measure intraluminal pH and test the idea that ANO1/TMEM16A contributes to
luminal pH balance. Our data show that, under physiologically relevant
stimulation with 10 pm cholesystokinin, the luminal acid load that results from
the exocytic fusion of zymogen granules is significantly blunted by HCO3 (-)
buffer in comparison with HEPES, and that this is blocked by the specific TMEM16A
inhibitor T16inh-A01. Furthermore, in a model of acute pancreatitis, we observed
substantive luminal acidification and provide evidence that ANO1/TMEM16A acts to
attenuate this pH shift. We conclude that ANO1/TMEM16A is a significant pathway
in pancreatic acinar cells for HCO3 (-) secretion into the lumen.
PMID- 27510034
TI - Phosphatidic Acid Produced by RalA-activated PLD2 Stimulates Caveolae-mediated
Endocytosis and Trafficking in Endothelial Cells.
AB - Caveolae are the primary route for internalization and transendothelial transport
of macromolecules, such as insulin and albumin. Caveolae-mediated endocytosis is
activated by Src-dependent caveolin-1 (Cav-1) phosphorylation and subsequent
recruitment of dynamin-2 and filamin A (FilA), which facilitate vesicle fission
and trafficking, respectively. Here, we tested the role of RalA and phospholipase
D (PLD) signaling in the regulation of caveolae-mediated endocytosis and
trafficking. The addition of albumin to human lung microvascular endothelial
cells induced the activation of RalA within minutes, and siRNA-mediated down
regulation of RalA abolished fluorescent BSA uptake. Co-immunoprecipitation
studies revealed that albumin induced the association between RalA, Cav-1, and
FilA; however, RalA knockdown with siRNA did not affect FilA recruitment to Cav
1, suggesting that RalA was not required for FilA and Cav-1 complex formation.
Rather, RalA probably facilitates caveolae-mediated endocytosis by activating
downstream effectors. PLD2 was shown to be activated by RalA, and inhibition of
PLD2 abolished Alexa-488-BSA uptake, indicating that phosphatidic acid (PA)
generated by PLD2 may facilitate caveolae-mediated endocytosis. Furthermore,
using a PA biosensor, GFP-PASS, we observed that BSA induced an increase in PA co
localization with Cav-1-RFP, which could be blocked by a dominant negative PLD2
mutant. Total internal reflection fluorescence microscopy studies of Cav-1-RFP
also showed that fusion of caveolae with the basal plasma membrane was dependent
on PLD2 activity. Thus, our results suggest that the small GTPase RalA plays an
important role in promoting invagination and trafficking of caveolae, not by
potentiating the association between Cav-1 and FilA but by stimulating PLD2
mediated generation of phosphatidic acid.
PMID- 27510035
TI - Analyzing N-terminal Arginylation through the Use of Peptide Arrays and
Degradation Assays.
AB - Nalpha-terminal arginylation (Nt-arginylation) of proteins is mediated by the
Ate1 arginyltransferase (R-transferase), a component of the Arg/N-end rule
pathway. This proteolytic system recognizes proteins containing N-terminal
degradation signals called N-degrons, polyubiquitylates these proteins, and
thereby causes their degradation by the proteasome. The definitively identified
("canonical") residues that are Nt-arginylated by R-transferase are N-terminal
Asp, Glu, and (oxidized) Cys. Over the last decade, several publications have
suggested (i) that Ate1 can also arginylate non-canonical N-terminal residues;
(ii) that Ate1 is capable of arginylating not only alpha-amino groups of N
terminal residues but also gamma-carboxyl groups of internal (non-N-terminal) Asp
and Glu; and (iii) that some isoforms of Ate1 are specific for substrates bearing
N-terminal Cys residues. In the present study, we employed arrays of immobilized
11-residue peptides and pulse-chase assays to examine the substrate specificity
of mouse R-transferase. We show that amino acid sequences immediately downstream
of a substrate's canonical (Nt-arginylatable) N-terminal residue, particularly a
residue at position 2, can affect the rate of Nt-arginylation by R-transferase
and thereby the rate of degradation of a substrate protein. We also show that the
four major isoforms of mouse R-transferase have similar Nt-arginylation
specificities in vitro, contrary to the claim about the specificity of some Ate1
isoforms for N-terminal Cys. In addition, we found no evidence for a significant
activity of the Ate1 R-transferase toward previously invoked non-canonical N
terminal or internal amino acid residues. Together, our results raise technical
concerns about earlier studies that invoked non-canonical arginylation
specificities of Ate1.
PMID- 27510036
TI - Regulation of Neuronal Survival by Nucleophosmin 1 (NPM1) Is Dependent on Its
Expression Level, Subcellular Localization, and Oligomerization Status.
AB - NPM1 (nucleophosmin 1) is a nucleolar phosphoprotein that regulates many cellular
processes, including ribosome biogenesis, proliferation, and genomic integrity.
Although its role in proliferating cell types and tissues has been extensively
investigated, little is known about its function in neurons and in the brain
where it is highly expressed. We report that NPM1 protein expression is increased
selectively in the striatum in both the R6/2 transgenic and 3-nitropropionic acid
injected mouse models of Huntington's disease. Examination of the effect of
ectopic expression on cultured neurons revealed that increasing NPM1 is toxic to
otherwise healthy cerebellar granule and cortical neurons. Toxicity is dependent
on its cytoplasmic localization and oligomerization status. Forced retention of
NPM1 in the nucleus, as well as inhibiting its ability to oligomerize, not only
neutralizes NPM1 toxicity but also renders it protective against apoptosis.
Although not blocked by pharmacological inhibition of the pro-apoptotic
molecules, JNK, glycogen synthase kinase 3 beta, or caspases, toxicity is blocked
by compounds targeting cyclin-dependent kinases (CDKs), as well as by dominant
negative forms of CDK1 and CDK2 and the pan-CDK inhibitor, p21(Cip1/Waf1)
Although induced in in vivo Huntington's disease models, NPM1 protein levels are
unchanged in cultured cerebellar granule and cortical neurons induced to die by
low potassium or homocysteic acid treatment, respectively. Moreover, and
counterintuitively, knockdown of its expression or inhibition of endogenous NPM1
oligomerization in these cultured neurons is toxic. Taken together, our study
suggests that although neurons need NPM1 for survival, an increase in its
expression beyond physiological levels and its translocation to the cytoplasm
leads to death through abortive cell cycle induction.
PMID- 27510037
TI - Acidic pH Is a Metabolic Switch for 2-Hydroxyglutarate Generation and Signaling.
AB - 2-Hydroxyglutarate (2-HG) is an important epigenetic regulator, with potential
roles in cancer and stem cell biology. The d-(R)-enantiomer (d-2-HG) is an
oncometabolite generated from alpha-ketoglutarate (alpha-KG) by mutant isocitrate
dehydrogenase, whereas l-(S)-2-HG is generated by lactate dehydrogenase and
malate dehydrogenase in response to hypoxia. Because acidic pH is a common
feature of hypoxia, as well as tumor and stem cell microenvironments, we
hypothesized that pH may regulate cellular 2-HG levels. Herein we report that
cytosolic acidification under normoxia moderately elevated 2-HG in cells, and
boosting endogenous substrate alpha-KG levels further stimulated this elevation.
Studies with isolated lactate dehydrogenase-1 and malate dehydrogenase-2 revealed
that generation of 2-HG by both enzymes was stimulated severalfold at acidic pH,
relative to normal physiologic pH. In addition, acidic pH was found to inhibit
the activity of the mitochondrial l-2-HG removal enzyme l-2-HG dehydrogenase and
to stimulate the reverse reaction of isocitrate dehydrogenase (carboxylation of
alpha-KG to isocitrate). Furthermore, because acidic pH is known to stabilize
hypoxia-inducible factor (HIF) and 2-HG is a known inhibitor of HIF prolyl
hydroxylases, we hypothesized that 2-HG may be required for acid-induced HIF
stabilization. Accordingly, cells stably overexpressing l-2-HG dehydrogenase
exhibited a blunted HIF response to acid. Together, these results suggest that
acidosis is an important and previously overlooked regulator of 2-HG accumulation
and other oncometabolic events, with implications for HIF signaling.
PMID- 27510038
TI - Developmental delay and failure to thrive in a 7-month-old baby boy with
spontaneous transient Graves' thyrotoxicosis: a case report.
AB - BACKGROUND: Thyroid dysfunction can induce developmental delay and failure to
thrive in infancy. Congenital hypothyroidism is one of the common causes of these
symptoms in infancy. By contrast, hyperthyroidism is a rare cause of these
symptoms in infancy. CASE PRESENTATION: A 7-month-old Japanese baby boy was
examined for developmental delay and failure to thrive. Blood tests were
performed, which showed low levels of thyroid-stimulating hormone (<0.01 MUU/mL)
and high levels of free thyroxine (2.14 pg/mL). He was referred to our hospital
at 8 months of age. His height was 64 cm (-2.7 standard deviation) and his weight
was 6085 g (-2.5 standard deviation). No goiter was detected on examination. His
thyrotropin receptor antibody was slightly high (3.9 IU/L), whereas thyroid
stimulating antibody, anti-thyroglobulin antibody, and thyroid peroxidase
antibody were within normal range. These blood findings indicated
hyperthyroidism, most likely Graves' disease. His free thyroxine level decreased
in the first month after our examination. No increased vascularity of his thyroid
gland was noted. The technetium uptake of his thyroid gland in scintigraphy was
relatively increased compared to the intake of his salivary gland. We elected to
observe rather than treat with anti-thyroid medications. CONCLUSION: We have to
rule out spontaneous transient Graves' thyrotoxicosis when babies have symptoms
of developmental delay and fail to thrive.
PMID- 27510040
TI - Aortitis as a cause of severe abdominal pain.
PMID- 27510039
TI - Q&A: Auxin: the plant molecule that influences almost anything.
AB - Auxin is an essential molecule that controls almost every aspect of plant
development. Although the core signaling components that control auxin response
are well characterized, the precise mechanisms enabling specific responses are
not yet fully understood. Considering the significance of auxin in plant growth
and its potential applications, deciphering further aspects of its biology is an
important and exciting challenge.
PMID- 27510041
TI - Recent advances in the biomimicry of structural colours.
AB - Nature has mastered the construction of nanostructures with well-defined
macroscopic effects and purposes. Structural colouration is a visible consequence
of the particular patterning of a reflecting surface with regular structures at
submicron length scales. Structural colours usually appear bright, shiny,
iridescent or with a metallic look, as a result of physical processes such as
diffraction, interference, or scattering with a typically small dissipative loss.
These features have recently attracted much research effort in materials science,
chemistry, engineering and physics, in order to understand and produce structural
colours. In these early stages of photonics, researchers facing an infinite array
of possible colour-producing structures are heavily inspired by the elaborate
architectures they find in nature. We review here the recent technological
strategies employed to artificially mimic the structural colours found in nature,
as well as some of their current and potential applications.
PMID- 27510042
TI - Solanum tuberosum L. cv Hongyoung extract inhibits 2,4-dinitrochlorobenzene
induced atopic dermatitis in NC/Nga mice.
AB - Solanum tuberosum L. cv Hongyoung (SH) is a widely consumed anthocyanin-rich food
and medicinal plant, which possesses anti-inflammatory and anti-allergic
activities. The present study aimed to examine the inhibitory effects of SH
extract on atopic dermatitis (AD)-like skin lesions induced by the topical
application of 2,4-dinitrochlorobenzene (DNCB) in NC/Nga mice. SH extract was
orally administered to the DNCB-treated NC/Nga mice. The anti-AD effects of SH
extract were examined by measuring symptom severity; ear thickness; scratching
behavior; serum levels of immunoglobulin (Ig)E; T-helper (Th)1, Th2 and Th17
cytokine levels in the spleen; mRNA expression levels of inflammatory cytokines
and chemokines; and tissue infiltration of inflammatory cells. The results
demonstrated that SH extract inhibited the development of AD-like lesions, and
reduced IgE levels and the production of cytokines. Furthermore, SH extract
significantly suppressed the expression of AD-associated mRNAs in lesional skin.
Histological alterations in the AD-like lesions were visualized using hematoxylin
and eosin, and toluidine blue staining in the DNCB-treated group; the alterations
were attenuated following SH treatment. In addition, thickening of the epidermis
and accumulation of inflammatory cells in the DNCB-treated mice were suppressed
by SH treatment. These results suggested that SH extract may suppress the
development of AD symptoms through modulation of the Th1 and Th2 responses.
PMID- 27510090
TI - Martin Erhard - upper world and underworld. Order and perversion.
PMID- 27510093
TI - Phosphine-catalyzed cage carbon functionalization of o-carborane: facile
synthesis of alkenylcarboranes.
AB - A phosphine-catalyzed alkenylation reaction of o-carborane with electron
deficient alkynes at the C-H vertex of the o-carborane cage has been developed,
which led to the preparation of a series of 1-alkenyl-o-carboranes in moderate to
very good yields with excellent regio- and stereoselectivity. This highly
efficient and simple method represents the first example of organophosphine
catalyzed C-H functionalization of o-carborane.
PMID- 27510092
TI - cDICE method produces giant lipid vesicles under physiological conditions of
charged lipids and ionic solutions.
AB - Giant unilamellar vesicles are a powerful and common tool employed in biophysical
studies of lipid membranes. Here we evaluate a recently introduced method of
vesicle formation, "continuous droplet interface crossing encapsulation" (cDICE).
This method produces monodisperse giant unilamellar vesicles of controlled sizes
and high encapsulation efficiencies, using readily available instrumentation. We
find that mixtures of phospholipids within vesicle membranes produced by cDICE
undergo phase separation at the same characteristic temperatures as lipids in
vesicles formed by a complementary technique. We find that the cDICE method is
effective both when vesicles are produced from charged lipids and when the
surrounding buffer contains a high concentration of salt. A shortcoming of the
technique is that cholesterol is not substantially incorporated into vesicle
membranes.
PMID- 27510094
TI - MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes
the proliferation and invasion of ovarian cancer cells.
AB - Ovarian cancer is a leading cause of malignant gynecological tumor-related
mortality among women. The treatment of ovarian cancer patients continues to be
challenging. MicroRNA-106a (miR-106a) is widely expressed in diverse human
tumors. In the present study, we investigated the biological and pathological
roles of miR-106a in ovarian cancers. We found that miR-106a expression was
significantly increased in primary ovarian cancer tissues and ovarian cancer
cells compared with the level in normal tissues. Ectopic expression of an miR
106a inhibitor attenuated ovarian cancer cell proliferation and invasion. miR
106a promoted the growth and invasion of SKOV3 cells by targeting phosphatase and
tensin homolog (PTEN). Furthermore, the present study revealed that IL-6
inhibited miR-106a expression by activating STAT3. Tocilizumab, a humanized anti
human IL-6R antibody, that competitively inhibits IL-6/IL-6R signaling, did not
inhibit the proliferation and invasion of SKOV3 cells. In conclusion, our studies
revealed that miR-106a was significantly increased in the ovarian cancer tissues
and cell lines. Downregulation of the expression of miR-106a inhibited cell
growth and metastasis of ovarian cancer cells. Together, the present study
suggests that miR-106a acts as an oncogene in ovarian cancers.
PMID- 27510095
TI - Transforming healthcare through regenerative medicine.
AB - Regenerative medicine therapies, underpinned by the core principles of
rejuvenation, regeneration and replacement, are shifting the paradigm in
healthcare from symptomatic treatment in the 20th century to curative treatment
in the 21st century. By addressing the reasons behind the rapid expansion of
regenerative medicine research and presenting an overview of current clinical
trials, we explore the potential of regenerative medicine to reshape modern
healthcare.
PMID- 27510097
TI - Scaling and automation of a high-throughput single-cell-derived tumor sphere
assay chip.
AB - Recent research suggests that cancer stem-like cells (CSCs) are the key
subpopulation for tumor relapse and metastasis. Due to cancer plasticity in
surface antigen and enzymatic activity markers, functional tumorsphere assays are
promising alternatives for CSC identification. To reliably quantify rare CSCs (1
5%), thousands of single-cell suspension cultures are required. While
microfluidics is a powerful tool in handling single cells, previous works provide
limited throughput and lack automatic data analysis capability required for high
throughput studies. In this study, we present the scaling and automation of high
throughput single-cell-derived tumor sphere assay chips, facilitating the
tracking of up to ~10 000 cells on a chip with ~76.5% capture rate. The presented
cell capture scheme guarantees sampling a representative population from the bulk
cells. To analyze thousands of single-cells with a variety of fluorescent
intensities, a highly adaptable analysis program was developed for cell/sphere
counting and size measurement. Using a Pluronic(r) F108 (poly(ethylene glycol)
block-poly(propylene glycol)-block-poly(ethylene glycol)) coating on
polydimethylsiloxane (PDMS), a suspension culture environment was created to test
a controversial hypothesis: whether larger or smaller cells are more stem-like
defined by the capability to form single-cell-derived spheres. Different cell
lines showed different correlations between sphere formation rate and initial
cell size, suggesting heterogeneity in pathway regulation among breast cancer
cell lines. More interestingly, by monitoring hundreds of spheres, we identified
heterogeneity in sphere growth dynamics, indicating the cellular heterogeneity
even within CSCs. These preliminary results highlight the power of unprecedented
high-throughput and automation in CSC studies.
PMID- 27510096
TI - NO* and Pancreatic Cancer: A Complex Interaction with Therapeutic Potential.
AB - SIGNIFICANCE: Pancreatic tumors express high level of nitric oxide synthases
(NOSs) in particular inducible (iNOS/NOS2) and endothelial (eNOS/NOS3) forms.
However, the role of nitric oxide (NO*) in the development and progression of
pancreatic cancer is not clearly defined. Delineating the NO*-induced signaling
in pancreatic cancer and its potential contribution in disease aggressiveness may
provide therapeutic targets to improve survival in this lethal malignancy. Recent
Advances: An increased expression of NOS2/iNOS in tumors is associated with
poorer survival in early stage resected patients with pancreatic ductal
adenocarcinoma (PDAC). Furthermore, genetic deletion of NOS2 enhanced survival in
mice with autochthonous PDAC. Additionally, targeting NOS3/eNOS reduced the
abundance of precursor lesions in mice, which trended toward improved survival.
CRITICAL ISSUES: The extremely poor prognosis in pancreatic cancer is due to the
late diagnosis and lack of effective therapy in advanced disease. One of the most
critical issues is to decipher the underlying mechanism of disease aggressiveness
and therapeutic resistance for identifying potential therapeutic target and
effective treatment. Given the evidence of a strong association between
inflammation and pancreatic cancer and clinical evidence, which suggests an
association between NOS2 and disease aggressiveness, it is critical to define the
role of NO* signaling in this lethal malignancy. FUTURE DIRECTIONS: Recent
preclinical and clinical evidences indicate a potential therapeutic significance
of targeting NO* signaling in pancreatic cancer. With the emergence of new
preclinical models, including the patient-derived organoids, further preclinical
evaluation using clinically tested NOS inhibitors is needed for designing future
clinical investigation. Antioxid. Redox Signal. 26, 1000-1008.
PMID- 27510098
TI - Slow Intramolecular Vibrational Relaxation Leads to Long-Lived Excited-State
Wavepackets.
AB - Broadband optical pump and compressed white light continuum probe were used to
measure the transient excited-state absorption, ground-state bleach, and
stimulated emission signals of cresyl violet solution in methanol. Amplitude
oscillations caused by wavepacket motion in the ground and excited electronic
states were analyzed. It was found that vibrational coherences in the excited
state persist for more than the experimental waiting time window of 6 ps, and the
strongest mode had a dephasing time constant of 2.4 ps. We hypothesize the
dephasing of the wavepacket in the excited state is predominantly caused by
intramolecular vibrational relaxation (IVR). Slow IVR indicates weak mode-mode
coupling and therefore weak anharmonicity of the potential of this vibration.
Thus, the initially prepared vibrational wavepacket in the excited state is not
significantly perturbed by nonadiabatic coupling to other electronic states, and
hence the diabatic and adiabatic representations of the system are essentially
identical within the Born-Oppenheimer approximation. The wavepacket therefore
evolves with time in an almost harmonic potential, slowly dephased by IVR and the
pure vibrational decoherence. The consistency in the position of node (phase
change in the wavepacket) in the excited-state absorption and stimulated emission
signals without undergoing any frequency shift until the wavepacket is completely
dephased conforms to the absence of any reactive internal conversion.
PMID- 27510152
TI - Application of ADA1 as a new marker enzyme in sandwich ELISA to study the effect
of adenosine on activated monocytes.
AB - Enzyme-linked immunosorbent assay (ELISA) is a valuable technique to detect
antigens in biological fluids. Horse radish peroxidase (HRP) is one of the most
common enzymes used for signal amplification in ELISA. Despite new advances in
technology, such as a large-scale production of recombinant enzymes and
availability of new detection systems, limited research is devoted to finding
alternative enzymes and their substrates to amplify the ELISA signals. Here, HRP
avidin was substituted with the human adenosine deaminase (hADA1)-streptavidin
complex and adenosine as a detection system in commercial ELISA kits. The hADA1
ELISA was successfully used to demonstrate that adenosine, bound to A1 and A3
adenosine receptors, increases cytokine secretion by LPS activated monocytes. We
show that hADA1-based ELISA has the same sensitivity, and also provides identical
results, as HRP ELISA. In addition, the sensitivity of hADA1-based ELISA could be
easily adjusted by changing the adenosine concentration and the incubation time.
Therefore, hADA1 could be used as a detection enzyme with any commercial ELISA
kit with a wide range of concentration of antigens.
PMID- 27510153
TI - Structural and electronic features of small hybrid organic-inorganic halide
perovskite clusters: a theoretical analysis.
AB - We herein present the results of a series of calculations performed on some
representative cluster models of hybrid organic-inorganic halide perovskites,
(MA)jPbkXl (l = 2j + k; MA = methylammonium, +CH3NH3; X = halide). In particular,
aimed at finding possible analogies with the bulk, we focused our initial
attention on neutral clusters of iodides (X = I) constituted by an increasing
number of Pb atoms (k = 1, 2, 8, 12). For the single octahedron (k = 1), we
similarly extended our calculations to mixed Br-/I-terminated and fully Br
terminated octahedra, finding similar miscibilities for the two dimensionally
different systems (i.e., the cluster and bulk). When increasing the size of the
models, we found an unequivocally evident relationship between the total
dielectric dipole moment of the investigated cluster and the wavefunction spatial
distribution of the frontier molecular orbitals. This result rationalizes the
structural and electronic properties of such zero-dimensional systems and
supports the results previously obtained via linear scaling ab initio methods for
very large supercells, i.e., the localization at the nanoscale of the
wavefunction of the frontier orbitals as a function of the local fluctuations of
the potential, which are mainly associated with the organic cation orientation.
PMID- 27510154
TI - Congenital absence of infrarenal inferior vena cava and deep veins of the lower
limbs: a case report.
AB - BACKGROUND: Congenital anomalies of the venous system are known but congenital
absence of infrarenal inferior vena cava with absent deep venous system of the
lower limbs is extremely rare. CASE PRESENTATION: We report the case of an 11
year-old Indian girl who presented with large venous collaterals on her anterior
abdominal wall and recurrent non-healing venous ulcers on her left leg with
complete absence of infrarenal inferior vena cava and absent deep veins of her
lower limbs. CONCLUSIONS: Congenital absence of infrarenal inferior vena cava may
occur with absence of the deep venous system of the lower limbs. We have reported
this case because of its extreme rarity and to enhance awareness of this entity
that has no treatment currently.
PMID- 27510156
TI - [Longterm risk subtotal splenectomy?]
PMID- 27510155
TI - [Complications after thyroid gland operations in Germany : A routine data
analysis of 66,902 AOK patients].
AB - BACKGROUND: Routine data from hospitals in the public healthcare system allow the
analysis of large patient datasets without generating additional documentation
efforts for hospitals. This study reports the frequencies of postoperative
complications after thyroid surgery based on routine nationwide data. Moreover,
volume-outcome relationships were investigated. MATERIAL AND METHODS: Nationwide
routine data from insured patients of the Local Health Insurance Fund (AOK) who
underwent thyroid surgery between 2008 and 2010 were analyzed. Complications were
determined based on indicators for permanent vocal cord palsy, re-bleeding with
re-operations and wound infections with specific treatment. The effect of
hospital volumes (volume quintiles) on the indicators was determined by
multivariate logistic regression. RESULTS: A total of 66,902 thyroid gland
operations were identified. The overall frequency of permanent vocal cord palsy
was 1.5 %, re-bleeding 1.8 % and wound infections 0.4 %. In the four lowest case
volume categories the risk of permanent vocal cord palsy was significantly higher
compared to the highest case volume hospitals (odds ratio 1.5, 1.7, 1.7 and 2.2,
respectively). CONCLUSION: This study represents the reality of healthcare for
thyroid surgery in Germany. Additionally, it was determined that the risk for
permanent vocal cord palsy after thyroid gland operations decreased with
increasing case volumes of hospitals.
PMID- 27510157
TI - Determinants of patients' needs in asthma treatment: a cross-sectional study.
AB - Patients' needs in asthma remain insufficiently understood and met. We therefore
aimed to investigate the potential determinants of patients' needs in asthma
treatment. Our study was based on survey data on 189 adults with asthma. Needs
were measured using the 13-item Needs in Asthma Treatment questionnaire, which
yields a total score and subscale-specific scores ('exacerbations', 'patient
expertise', 'handling drugs' and 'drug effects'). We considered age, sex,
education, years since diagnosis and anxiety/depression (measured by the Patient
Health Questionnaire-4) as potential determinants. Associations were estimated by
multivariable linear regression. Overall, we observed that younger age, poor
mental health and a more recently established asthma diagnosis were independently
associated with increased needs. Information on drug effects was an exception to
this pattern as the need in that domain was solely determined by sex (being
greater in men). In conclusion, our study provides novel evidence on patient
characteristics that are associated with needs in asthma treatment. If confirmed
by future studies, our observations may assist healthcare professionals to
identify asthma patients with potentially elevated information, support and
training needs and could contribute to the development of tailored interventions.
PMID- 27510158
TI - Inhibitory effects of B-cell translocation gene 2 on skin cancer cells via the
Wnt/beta-catenin signaling pathway.
AB - B-cell translocation gene 2 (BTG2), a tumor suppressor gene, is downregulated in
several types of human cancer cell. However, its function in skin cancer cells
has not been fully elucidated. Therefore, the present study investigated the
expression and function of BTG2 in skin cancer cells, and investigated the
underlying molecular mechanism. The results indicated that BTG2 expression was
downregulated in skin cancer cell lines. Overexpression of BTG2 significantly
inhibited cell proliferation, cell cycle progression, and the invasion and
migration of skin cancer cells. Furthermore, it was determined that
overexpression of BTG2 significantly decreased the protein expression levels of
beta-catenin, cyclin D1 and v-myc avian myelocytomatosis viral oncogene homolog
in skin cancer cells. This suggests that BTG2 may function as a tumor suppressor
by interfering with the Wnt/beta-catenin signaling pathway in skin cancer cells.
Thus, novel therapeutic strategies and agents targeting BTG2 may be potential
treatments for skin cancer.
PMID- 27510160
TI - Lead line in rodents: an old sign of lead intoxication turned into a new method
for environmental surveillance.
AB - The "lead line" was described by Henry Burton in 1840. Rodents are used as
sentinels to monitor environmental pollution, but their teeth have not been used
to determine lead. To determine whether lead deposits can be observed in the
teeth of lead-exposed animals, since the gingival deposits known as "lead line"
would likely have a correlate in the calcified tissue to which the gums are
opposed during life. Male Wistar rats were exposed to lead in the drinking water
(30 mg/L) since birth until 60 days-old. Molars and the incisors of each
hemimandible were analyzed by scanning electron microscopy (SEM) on regular and
backscattered electrons (BSE) mode. Elements were determined using electron
dispersive spectroscopy (EDS). Clean cervical margins were observed on control
teeth, as opposed to the findings of extensive deposits on lead-exposed animals,
even in hemimandibles that had been exhumed after being buried for 90 days.
BSE/EDS indicated that those deposits were an exogenous material compatible with
lead sulfite. Presence of calcium, phosphorus, magnesium, carbon, lead, and
oxygen is presented. Lead-exposed animals presented marked root resorption. The
lead deposits characterized here for the first time show that the "lead line"
seen in gums has a calcified tissue counterpart, that is detectable post-mortem
even in animals exposed to a low dose of lead. This is likely a good method to
detect undue lead exposure and will likely have wide application for pollution
surveillance using sentinels.
PMID- 27510161
TI - Evaluation of the performances of a biological treatment on tin-enriched bronze.
AB - Recently, research gives emphasis to eco-friendly and sustainable approaches for
the preservation of cultural heritage that could offer advantages in terms of
compatibility, durability and safety. Hence, a biological treatment, based on a
specific fungal strain of Beauveria bassiana, is exploited for the stabilization
of soluble and/or active bronze corrosion products, converting them into copper
oxalates. The chemical stability of the latter represents a real improvement for
the long-term preservation of bronze, especially in case of exposure to acid
rain. However, the corrosion behaviour of bronze differs from that of pure copper
due to the presence of additional alloying elements. In natural environments, the
selective dissolution of copper leads to a relative tin-enrichment within the
corrosion layers, mostly in unsheltered areas exposed to rainwater runoff. To
understand the influence of tin-enrichment on the formation of oxalates, pure tin
and artificially tin-enriched bronze coupons were treated with this novel
biological system and, in the case of bronze coupons, exposed to accelerated
ageing. Tin enrichment and accelerated ageing were performed through runoff
tests. Before and after treatment and ageing, the sample surface was
characterized through Fourier transform infrared (FTIR) and Raman spectroscopies,
scanning electron microscopy coupled to energy dispersive spectroscopy (SEM-EDS).
Metals released in the ageing solutions were analysed through atomic absorption
spectrometry (AAS). The analytical results allowed to better understand the
response of unsheltered areas from outdoor bronze monuments to the biological
treatment proposed.
PMID- 27510159
TI - Hepatic and serum lipid signatures specific to nonalcoholic steatohepatitis in
murine models.
AB - Nonalcoholic fatty liver (NAFL) is a precursor of nonalcoholic steatohepatitis
(NASH), a condition that may progress to cirrhosis and hepatocellular carcinoma.
Markers for diagnosis of NASH are still lacking. We have investigated lipid
markers using mouse models that developed NAFL when fed with high fat diet (HFD)
or NASH when fed using methionine choline deficient diet (MCDD). We have
performed a comprehensive lipidomic analysis on liver tissues as well as on sera
from mice fed HFD (n = 5), MCDD (n = 5) or normal diet as controls (n = 10).
Machine learning approach based on prediction analysis of microarrays followed by
random forests allowed identifying 21 lipids out of 149 in the liver and 14
lipids out of 155 in the serum discriminating mice fed MCDD from HFD or controls.
In conclusion, the global approach implemented allowed characterizing lipid
signatures specific to NASH in both liver and serum from animal models. This
opens new avenue for investigating early and non-invasive lipid markers for
diagnosis of NASH in human.
PMID- 27510162
TI - Advanced oxidative processes and membrane separation for micropollutant removal
from biotreated domestic wastewater.
AB - The presence of micropollutants in sewage is already widely known, as well as the
effects caused by natural and synthetic hormones. Thus, it is necessary to apply
treatments to remove them from water systems, such as advanced oxidation
processes (AOPs) and membrane separation processes, which can oxidize and remove
high concentrations of organic compounds. This work investigated the removal of
17beta-estradiol (E2), 17alpha-ethinylestradiol (EE2), and estriol (E3) from
biotreated sewage. Reverse osmosis processes were conducted at three recoveries
(50, 60, and 70 %). For E2 and EE2, the removals were affected by the recovery.
The best results for RO were as follows: the E2 compound removal was 89 % for 60
% recovery and the EE2 compound removal was 57 % for 50 % recovery. The RO
recovery did not impact the E3 removal. It was concluded that the interaction
between the evaluated estrogens, and the membrane was the major factor for the
hormone separation. The AOP treatment using H2O2/UV was carried out in two
sampling campaigns. First, we evaluated the variation of UV doses (24.48, 73.44,
122.4, and 244.8 kJ m-2) with 18.8 mg L-1 of H2O2 in the reaction. EE2 showed
considerable removals (around 70 %). In order to optimize the results, an
experimental design was applied. The best result was obtained with higher UV dose
(122.4 kJ m-2) and lower H2O2 concentration (4 mg L-1), achieving removal of 91 %
for E3 and 100 % for E2 and EE2.
PMID- 27510163
TI - Comparison of single extraction procedures and the application of an index for
the assessment of heavy metal bioavailability in river sediments.
AB - Metals in sediments are present in different chemical forms which affect their
ability to transfer. The objective of this body of work was to compare different
extraction methods for the bioavailability evaluation of some elements, such as
Ba, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Ni, Pb, V and Zn from Serbian river sediments.
A bioavailability risk assessment index (BRAI) was used for the quantification of
heavy metal bioavailability in the sediments. Actual and potential element
availability was assessed by single extractions with mild (CaCl2 and CH3COONH4)
and acidic (CH3COOH) extractants and complexing agents (EDTA). Aqua regia
extraction was used for the determination of the pseudo-total element content in
river sediments. In different single extraction tests, higher extraction of Cd,
Cu, Zn and Pb was observed than for the other elements. The results of the single
extraction tests revealed that there is a considerable chance of metal leaching
from the sediments assessed in this study. When the BRAI was applied, the results
showed a high risk of heavy metal bioavailability in Serbian river sediments.
PMID- 27510164
TI - Antibiotic resistance, efflux pump genes and virulence determinants in
Enterococcus spp. from surface water systems.
AB - The aim of this study was to report on antibiotic susceptibility patterns as well
as highlight the presence of efflux pump genes and virulence genetic determinants
in Enterococcus spp. isolated from South African surface water systems. One
hundred and twenty-four Enterococcus isolates consisting of seven species were
identified. Antimicrobial susceptibility testing revealed a high percentage of
isolates was resistant to beta-lactams and vancomycin. Many were also resistant
to other antibiotic groups. These isolates were screened by PCR, for the presence
of four efflux pump genes (mefA, tetK, tetL and msrC). Efflux genes mefA and tetK
were not detected in any of the Enterococcus spp. However, tetL and msrC were
detected in 17 % of the Enterococcus spp. The presence of virulence factors in
the Enterococcus spp. harbouring efflux pump genes was determined. Virulence
determinants were detected in 86 % of the Enterococcus spp. harbouring efflux
pump genes. Four (asa1, cylA, gel and hyl) of the five virulence factors were
detected. The findings of this study have demonstrated that Enterococcus from
South African surface water systems are resistant to multiple antibiotics, some
of which are frequently used for therapy. Furthermore, these isolates harbour
efflux pump genes coding for resistance to antibiotics and virulence factors
which enhance their pathogenic potential.
PMID- 27510165
TI - Efficacy of Bt maize producing the Cry1Ac protein against two important pests of
corn in China.
AB - Ostrinia furnacalis (Guenee) and Helicoverpa armigera (Hubner) are the most
important pests of maize in China. A laboratory study and a 2-year field study on
the efficacy of transgenic maize expressing the Cry1Ac protein BT38 against O.
furnacalis and H. armigera were performed. We found that the husks, kernels, and
silks of BT38 showed significant efficacy against larvae of O. furnacalis and H.
armigera. In the field, when neonate larvae of O. furnacalis and H. armigera were
on plants at different growth stages and when levels of leaf-damage or number of
damaged silks were used to score efficacy, we found that BT38 showed significant
insecticidal efficacy against O. furnacalis and H. armigera, but the non-Bt maize
did not show significant efficacy against either pest. These results suggest that
the insecticidal efficacy of Bt maize expressing the Cry1Ac protein could be
useful in the integrated pest management of these key maize pests.
PMID- 27510166
TI - Bio- and toxic elements in edible wild mushrooms from two regions of potentially
different environmental conditions in eastern Poland.
AB - In the present study, the composition of bio-elements (K, Na, Mg, Ca, Fe, Cu, Zn)
and toxic elements (Ag, Cd) in seven edible mushrooms from the rural and woodland
region of Morag (north-eastern Poland) and the rural and industrial region of the
Tarnobrzeska Upland (south-eastern Poland) were investigated using a validated
method. The species examined were Boletus edulis, Cantharellus cibarius, Leccinum
aurantiacum, Leccinum versipelle, Lycoperdon perlatum, Suillus luteus, and
Xerocomus subtomentosus. Final determination was carried out by flame atomic
absorption spectroscopy (FAAS) after microwave-assisted decomposition of sample
matrices with solutions of concentrated nitric acid in the pressurized
polytetrafluoroethylene vessels. The contents of the alkali elements and alkali
earth elements were determined in the species surveyed. The alkali elements,
earth alkali elements, and transition metals (Ag, Cu, Zn, Fe, and Mn) were at
typical concentrations as was determined for the same or similar species
elsewhere in Poland and Europe. The results may suggest a lack of local and
regional emissions of those metallic elements from industrialization of some
sites in the Tarnobrzeska Plain. Cadmium was at elevated concentrations in L.
versipelle from the Tarnobrzeska Plain but the reason-pollution or geogenic
source-was unknown, while it was at typical concentrations in other species.
PMID- 27510167
TI - What can authors do for the papers they published in predatory journals?
PMID- 27510168
TI - The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction
by targeting glucocorticoid receptor function.
AB - Caffeine is associated with procognitive effects in humans by counteracting
overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the
human forebrain of aged and Alzheimer's disease (AD) patients. We have previously
shown that an anti-A2AR therapy reverts age-like memory deficits, by
reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and
corticosterone circadian levels. These observations suggest that A2AR over
activation and glucocorticoid dysfunction are key events in age-related
hippocampal deficits; but their direct connection has never been explored. We now
show that inducing A2AR overexpression in an aging-like profile is sufficient to
trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian
oscillation, and promotes reduction of GR hippocampal levels. The synaptic
plasticity and memory deficits triggered by GR in the hippocampus are amplified
by A2AR over-activation and were rescued by anti-A2AR therapy; finally, we
demonstrate that A2AR act on GR nuclear translocation and GR-dependent
transcriptional regulation. We provide the first demonstration that A2AR is a
major regulator of GR function and that this functional interconnection may be a
trigger to age-related memory deficits. This supports the idea that the
procognitive effects of A2AR antagonists, namely caffeine, on Alzheimer's and age
related cognitive impairments may rely on its ability to modulate GR actions.
PMID- 27510170
TI - A novel TBX20 loss-of-function mutation contributes to adult-onset dilated
cardiomyopathy or congenital atrial septal defect.
AB - Dilated cardiomyopathy (DCM) is the most prevalent form of primary cardiomyopathy
in humans and is a leading cause of heart failure and sudden cardiac death.
Genetic abnormalities have been demonstrated to be a major contributor to the
development of DCM. However, DCM is a genetically heterogeneous disease, and the
genetic basis underlying DCM in a significant proportion of patients remains
unclear. In the current study, the coding exons and splicing junction sites of
the T-Box 20 (TBX20) gene, which encodes a T-box transcription factor essential
for cardiac morphogenesis and structural remodeling, were sequenced in 115
unrelated patients with idiopathic DCM, and a novel heterozygous mutation,
p.E143X, was identified in one patient. Genetic analysis of the mutation
carrier's pedigree indicated that the nonsense mutation was present in all the
living family members with DCM, and also in a female patient with a congenital
atrial septal defect. The mutation, which was predicted to generate a truncated
protein with only the N-terminus and a fraction of the T-box domain remaining,
was absent in 800 control chromosomes. Functional assays using a dual-luciferase
reporter assay system revealed that the truncated TBX20 protein had no
transcriptional activity in contrast to its wild-type counterpart. Furthermore,
the mutation abolished the synergistic activation between TBX20 and NK2 homeobox
5, or between TBX20 and GATA binding protein 4. The observations of the current
study expand the mutation spectrum of TBX20 associated with DCM and congenital
heart disease (CHD), which provide novel insight into the molecular mechanisms
underlying DCM and CHD, suggesting the potential implications for the effective
and personalized treatment of these diseases.
PMID- 27510169
TI - Zika virus disease: a current review of the literature.
AB - BACKGROUND: The massive pandemic of Zika virus (ZIKV) infection is spreading
through South America, Central America, the Caribbean, and possibly the USA. It
is the most recent of four surprising appearances of imperative arthropod-borne
viral illnesses in the Western Hemisphere over the preceding 20 years. OBJECTIVE:
The objective of this narrative review is to summarize the existing knowledge
about the epidemiology, transmission, clinical manifestations, complications,
replication, pathogenesis, diagnosis, and treatment and prevention of ZIKV
infection. METHODS: We used electronic databases to identify relevant published
data regarding ZIKV in BOOLEAN and MeSH searches. CONCLUSION: This review
concludes that the ZIKV predominantly circulates in arboreal mosquitoes (e.g.,
Aedes africanus) and wild primates. It rarely causes severe infection in humans,
even in extremely enzootic regions. Currently, we do not have any efficacious
drugs against ZIKV infection. However, there are virus-specific therapeutic
targets, which may lead to the development of targeted anti-ZIKV drugs.
PMID- 27510171
TI - Retention in Porous Layer Pillar Array Planar Separation Platforms.
AB - This work presents the retention capabilities and surface area enhancement of
highly ordered, high-aspect-ratio, open-platform, two-dimensional (2D) pillar
arrays when coated with a thin layer of porous silicon oxide (PSO).
Photolithographically prepared pillar arrays were coated with 50-250 nm of PSO
via plasma-enhanced chemical vapor deposition and then functionalized with either
octadecyltrichlorosilane or n-butyldimethylchlorosilane. Theoretical calculations
indicate that a 50 nm layer of PSO increases the surface area of a pillar nearly
120-fold. Retention capabilities were tested by observing capillary-action-driven
development under various conditions, as well as by running one-dimensional
separations on varying thicknesses of PSO. Increasing the thickness of PSO on an
array clearly resulted in greater retention of the analyte(s) in question in both
experiments. In culmination, a two-dimensional separation of fluorescently
derivatized amines was performed to further demonstrate the capabilities of these
fabricated platforms.
PMID- 27510172
TI - How FSH and AMH reflect probabilities of oocyte numbers in poor prognosis
patients with small oocyte yields.
AB - In poor prognosis patients undergoing in vitro fertilization, advance
determinations of likely oocyte yields are especially important since oocyte
numbers to large degree determine in vitro fertilization cycle outcomes. Based on
baseline follicle stimulating hormone and anti-mullerian hormone levels at time
of initial presentation, we here, therefore, determined at all ages the
probabilities of obtaining 1->=5 oocytes in a retrospective analysis of 1554
consecutive patients undergoing in vitro fertilization cycles at an academically
affiliated private fertility center. At lowest levels (<=2.5 mIU/mL), Follicle
stimulating hormone at all ages was highly predictable for >=1 oocyte (88-96 %).
Probabilities declined and diverged between ages with increasing follicle
stimulating hormone, though narrowed again at high follicle stimulating hormone.
Anti-Mullerian hormone demonstrated at higher levels (2.5->=5 ng/ml) at all ages
almost perfect probabilities (99-100 %). With declining anti-Mullerian hormone,
age categories, however, increasingly diverged, though to lesser degree than
follicle stimulating hormone. In poor prognosis patients, follicle stimulating
hormone and anti-Mullerian hormone, thus, offer at different ages very specific
probabilities for retrieval of 1->=5 oocytes. Since oocyte numbers are associated
with embryo numbers, and numbers of transferable embryos with live birth rates,
here presented probability tables should facilitate improved prognostication of
poor prognosis patients. Discrepancies in here reported probabilities between
follicle stimulating hormone and anti-mullerian hormone also further define
follicle stimulating hormone and anti-mullerian hormone in their respective
abilities to represent functional ovarian reserve at different ages.
PMID- 27510173
TI - Physical exam in asymptomatic people drivers the detection of thyroid nodules
undergoing ultrasound guided fine needle aspiration biopsy.
AB - Understanding epidemiology and the factors leading to thyroid nodule diagnosis
might help alter the course of the thyroid cancer epidemic. Population-based
study using the Rochester Epidemiology Project database between 2003 and 2006.
Patients with thyroid nodules who underwent ultrasound guided fine needle
aspiration biopsy were included. We identified 453 patients with 520 thyroid
nodules undergoing ultrasound guided fine needle aspiration. Patients were mostly
women (n: 349, 77 %) with a mean age of 52 (standard deviation 17) years. The age
adjusted and sex-adjusted incidence of ultrasound guided fine needle aspiration
thyroid nodules between 2003 and 2006 was 89 (95 % confidence interval, 80-97)
per 100,000 person-years; the incidence in women was 130 (95 % confidence
interval, 117-144), and for men 43 (95 % confidence interval, 35-52) per 100,000
person-years. The incidence of ultrasound guided fine needle aspiration-thyroid
nodules increased by 42 %, from 68 (95 % confidence interval, 54-82) in 2003 to
97 (95 % confidence interval, 80-113) per 100,000 person-years in 2006. The group
with the highest incidence was patients between 70 and 79 years of age, 258 per
100,000 person-years. Most ultrasound guided fine needle aspiration-thyroid
nodules were found in asymptomatic patients (n: 371, 82 %) by physical
examination (n: 197, 43 %) or on imaging studies performed for non-thyroid issues
(n: 108, 24 %). Women were more likely to have nodules detected by palpation (45
%), whereas imaging and physical examination contributed similarly in men (39 and
38 %). There is a large and rapid increase in the ultrasound guided fine needle
aspiration-thyroid nodules, particularly among women and elderly patients which
mirrors the trends observed in thyroid cancer. Most thyroid nodules were found in
asymptomatic patients as a result of routine physical examination or imaging.
PMID- 27510174
TI - Lung Microtissue Array to Screen the Fibrogenic Potential of Carbon Nanotubes.
AB - Due to their excellent physical and chemical characteristics, multi-wall carbon
nanotubes (MWCNT) have the potential to be used in structural composites,
conductive materials, sensors, drug delivery and medical imaging. However,
because of their small-size and light-weight, the applications of MWCNT also
raise health concerns. In vivo animal studies have shown that MWCNT cause
biomechanical and genetic alterations in the lung tissue which lead to lung
fibrosis. To screen the fibrogenic risk factor of specific types of MWCNT, we
developed a human lung microtissue array device that allows real-time and in-situ
readout of the biomechanical properties of the engineered lung microtissue upon
MWCNT insult. We showed that the higher the MWCNT concentration, the more severe
cytotoxicity was observed. More importantly, short type MWCNT at low
concentration of 50 ng/ml stimulated microtissue formation and contraction force
generation, and caused substantial increase in the fibrogenic marker miR-21
expression, indicating the high fibrogenic potential of this specific carbon
nanotube type and concentration. The presented microtissue array system provides
a powerful tool for high-throughput examination of the therapeutic and
toxicological effects of target compounds in realistic tissue environment.
PMID- 27510175
TI - Clinical presentation of CAD and myocardial ischemia in women.
AB - Angina is the most frequent initial and subsequent manifestation of ischemic
heart disease in women. Women with stable ischemic heart disease have a more
diverse symptom presentation than men, with prominent anginal equivalents;
symptoms are more often precipitated by emotional or mental stress. Women,
especially at younger age, whose acute myocardial infarction presentation is
without chest pain have higher mortality rates than men without chest pain.
PMID- 27510176
TI - Comparison of the prognostic value of myocardial perfusion imaging using a CZT
SPECT camera with a conventional anger camera.
AB - BACKGROUND: Recent studies have shown that myocardial perfusion imaging (MPI) in
cadmium-zinc-telluride (CZT) cameras allow faster exams with less radiation dose
but there are little data comparing its prognosis information with that of
dedicated cardiac Na-I SPECT cameras OBJECTIVE: The objective of this study is to
compare the prognostic value of MPI using an ultrafast protocol with low
radiation dose in a CZT-SPECT and a traditional one. METHODS: Group 1 was
submitted to a two-day MIBI protocol in a conventional camera, and group 2 was
submitted to a 1-day MIBI protocol in CZT camera. MPI were classified as normal
or abnormal, and perfusion scores were calculated. Propensity score matching
methods were performed RESULTS: 3554 patients were followed during 33+/-8 months.
Groups 1 and 2 had similar distribution of age, gender, body mass index, risk
factors, previous revascularization, and use of pharmacological stress. Group 1
had more abnormal scans, higher scores than group 2. Annualized hard events rate
was higher in group 1 with normal scans but frequency of revascularization was
similar to normal group 2. Patients with abnormal scans had similar event rates
in both groups CONCLUSION: New protocol of MPI in CZT-SPECT showed similar
prognostic results to those obtained in dedicated cardiac Na-I SPECT camera, with
lower prevalence of hard events in patients with normal scan.
PMID- 27510177
TI - Effects of molecular chirality on self-assembly and switching in liquid crystals
at the cross-over between rod-like and bent shapes.
AB - A bent-core compound derived from a 4-cyanoresorcinol core unit with two
terephthalate based rod-like wings and carrying chiral 3,7-dimethyloctyloxy side
chains has been synthesized in racemic and enantiomerically pure form and
characterized by polarizing microscopy, differential scanning calorimetry, X-ray
diffraction and electro-optical investigations to study the influence of
molecular chirality on the superstructural chirality and polar order in lamellar
liquid crystalline phases. Herein we demonstrate that the coupling of molecular
chirality with superstructural layer chirality in SmCsPF domain phases (forming
energetically distinct diastereomeric pairs) can fix the tilt direction and thus
stabilize synpolar order, leading to bistable ferroelectric switching in the SmC*
phases of the (S)-enantiomer, whereas tristable modes determine the switching of
the racemate. Moreover, the mechanism of electric field induced molecular
reorganization changes from a rotation around the molecular long axis in the
racemate to a rotation on the tilt-cone for the (S)-enantiomer. At high
temperature the enantiomer behaves like a rod-like molecule with a chirality
induced ferroelectric SmC* phase and an electroclinic effect in the SmA'* phase.
At reduced temperature sterically induced polarization, due to the bent molecular
shape, becomes dominating, leading to much higher polarization values, thus
providing access to high polarization ferroelectric materials with weakly bent
compounds having only "weakly chiral" stereogenic units. Moreover, the field
induced alignment of the SmCsPF(()*()) domains gives rise to a special kind of
electroclinic effect appearing even in the absence of molecular chirality.
Comparison with related compounds indicates that the strongest effects of
chirality appear for weakly bent molecules with a relatively short coherence
length of polar order, whereas for smectic phases with long range polar order the
effects of the interlayer interfaces can override the chirality effects.
PMID- 27510178
TI - Identifying the position of the right atrium to align pressure transducer for CVP
: Spirit level or 3D electromagnetic positioning?
AB - The central venous pressure, CVP, is an important variable in the management of
selected perioperative and intensive care cases and in clinical decision support
systems, CDSS. In current routine, when measuring CVP the health care provider
may use anatomical landmarks and a spirit level, SL, to adjust the pressure
transducer to the level of the tricuspid valve, i.e. the phlebostatic axis. The
aim of the study was to assess the agreement in the postoperative setting between
the SL method and electromagnetic 3D positioning (EM). CVP was measured with
patients in positions dictated by nursing routines. The staff members measured
CVP using SL to position the transducer at the perceived phlebostatic level. This
position was compared to coordinates based on an electromagnetic field with
external sensors at anatomical landmarks and an internal sensor in the CV
catheter for 3D determination of the phlebostatic axis. An electronic survey took
bearing on the accepted error in measurement among colleagues at the department.
There was a clinically relevant difference between the CVP measured by the staff
members and the CVP based on the 3D EM positioning. The limits of agreement
extended in excess of +/-8 mmHg and half of the measurements had deviations
outside an accepted error range of +/-2.5 mmHg. There was a large variation in
CVP measurements when assessing the agreement with the current method. This may
indicate the need for improvement in accuracy, e.g. using the electromagnetic
field positioning system, in association with routine monitoring and clinical
decision support systems.
PMID- 27510179
TI - Selective expansion of regulatory T cells during lenalidomide treatment of
myelodysplastic syndrome with isolated deletion 5q.
AB - Lenalidomide (LEN) leads to erythroid improvement in the majority of patients
with myelodysplastic syndrome and isolated deletion of the long arm of chromosome
5 (MDS-del(5q)). This effect is believed to be exerted via its immunomodulatory
properties, although the precise nature is still incompletely understood. We
prospectively performed immune profiling in the bone marrow and blood of MDS
del(5q) patients undergoing LEN therapy for a median of 6 cycles. Therapy with
LEN led to a significant increase in the median absolute lymphocyte count (1.3
fold, p = 0.013) without changes in the distribution of the T helper cells within
the entire compartment. In parallel, the frequency of Treg increased
significantly during treatment both in the peripheral blood (5.0 vs. 9.6 %, p =
0.001) and bone marrow (3.4 vs. 8.1 %, p = 0.001). Surprisingly, LEN treatment
led to a decrease in TGFbeta levels, both in the peripheral blood (4.9 vs. 2.3
ng/ml, p = 0.039) and bone marrow (4.5 vs. 0.8 ng/ml, p = 0.023). These changes
were not associated with an increase in pro-inflammatory Th17 cells. Taken
together, our results demonstrate that LEN induces a shift in lymphocytic
populations towards immunosuppression in MDS-del(5q) patients.
PMID- 27510180
TI - Evaluation of neutrophil-lymphocyte ratio in patients with early-stage mycosis
fungoides.
AB - Neutrophil-lymphocyte ratio (NLR), an indicator of inflammation, has been lately
demonstrated as a prognostic factor and an indicator of disease activity in
various diseases. However, the effects of NLR have not been investigated in
mycosis fungoides (MF) patients yet. The aim of this study is to investigate the
relationship between the NLR and treatment demand (systemic PUVA and/or
chemotherapy), time to treatment, progression in stage, and time to progression
in stage in MF patients. The data of 117 patients, who were followed with the
diagnosis of MF at the Department of Dermatology in Istanbul Training and
Research Hospital between April 2006 and January 2016, were analyzed
retrospectively. The cutoff score for NLR was determined as 2 according to the
median NLR level which was 1.96. At the time of diagnosis, the median age of
patients was 54 years (range, 21-90) with 62 (53 %) female and 55 (47 %) male.
Seventy-seven (65.8 %) patients required treatment during follow-up. Sixty-three
(53.8 %) patients showed progression in disease stage. There was no significant
difference in treatment demand, time to treatment, progression in stage, and time
to progression in stage in patients with a NLR >= 2 and NLR < 2 (p = 0.331,
0.987, 0.065, and 0.119, respectively). It seems that there is no association
between the NLR and treatment demand, time to treatment, progression in stage,
and time to progression in stage in MF patients.
PMID- 27510181
TI - Screening of plasmid-mediated MCR-1 colistin-resistance from bacteremia.
PMID- 27510182
TI - Mutant prevention concentration of colistin alone and in combination with
rifampicin for multidrug-resistant Acinetobacter baumannii.
AB - Colistin-susceptible isolates of Acinetobacter baumannii often contain
subpopulations that are resistant to colistin. Monotherapy with colistin can lead
to selective growth of these subpopulations and emergence of colistin-resistant
strains. Our objectives were to explore the susceptibility pattern of colistin
resistant subpopulations and investigate if combining colistin with a second
antibiotic could prevent their selective growth. Four colistin-susceptible
clinical isolates of A. baumannii and one reference isolate were used. The mutant
prevention concentration (MPC) of colistin, i.e. the concentration required to
block growth of all single-step-mutant subpopulations, was determined by plating
an inoculum of 109 CFU on Mueller Hinton agar (MHA)-plates containing 2-fold
dilutions of colistin (0.125-128 mg/L). Susceptibility testing of colistin
resistant subpopulations, obtained in the MPC assay, was performed with Etest.
The MPC of colistin, in combination with rifampicin, was determined by plating an
inoculum of 109 CFU on MHA-plates containing colistin (0.125-128 mg/L) and fixed
concentrations of rifampicin (1.1 mg/L or 4.4 mg/L). The colistin-resistant
subpopulations demonstrated increased susceptibility to a number of agents
compared to their main populations. These subpopulations were even susceptible to
agents that normally are inactive against gram-negative bacteria and all had
rifampicin MICs of < 0.002 mg/L. The combination of colistin and rifampicin
completely inhibited the growth of all colistin-resistant subpopulations and
significantly lowered the MPC of colistin for A. baumannii. Combining colistin
with rifampicin could be a way to prevent selective growth of colistin-resistant
subpopulations of A. baumannii and possibly the emergence of colistin-resistant
strains.
PMID- 27510183
TI - Increased Mortality in Adult Cystic Fibrosis Patients with Medicaid Insurance
Awaiting Lung Transplantation.
AB - PURPOSE: Cystic fibrosis (CF) is a progressive disease resulting in end-stage
lung disease. Lung transplantation (LTx) is an important consideration in these
patients. Studies have suggested greater post-LTx mortality among CF patients
with public insurance. We evaluated the influence of insurance status on survival
among CF patients during their time on the LTx waitlist. METHODS: Adult LTx
candidates diagnosed with CF and listed since the implementation of the lung
allocation score, from May 2005 until September 2013, were identified in the
United Network for Organ Sharing database. Waitlist mortality was compared across
projected primary payment type (private insurance or self-pay; Medicaid;
Medicare) using Kaplan-Meier functions and Fine-Gray competing-risks survival
analysis, accounting for the competing risk of transplantation. RESULTS: 1770 LTx
candidates with CF were included in univariate survival analyses, with Medicaid
increasing waitlist mortality hazard relative to private insurance (HR 2.28; 95 %
CI 1.62, 3.21; p < 0.001) and relative to Medicare (HR 2.23; 95 % CI 1.43, 3.48;
p < 0.001). A multivariable competing-risks model confirmed greater waitlist
mortality among Medicaid patients relative to private insurance (HR 2.57; 95 % CI
1.56, 4.23; p < 0.001) or patients with Medicare (HR 4.02; 95 % CI 1.98, 8.17; p
< 0.001) after adjusting for potential confounders. No differences in waitlist
survival were found between Medicare and private insurance. CONCLUSIONS: CF
patients with Medicaid insurance have higher risk of death while awaiting LTx
when compared to patients with Medicare or private insurance. The impact of
insurance status on survival in this population begins before LTx and compounds
the disparities previously observed in post-transplant outcomes.
PMID- 27510184
TI - Core-shell Cd0.2Zn0.8S@BiOX (X = Cl, Br and I) microspheres: a family of hetero
structured catalysts with adjustable bandgaps, enhanced stability and
photocatalytic performance under visible light irradiation.
AB - Heterostructures consisting of two semiconductors have merited considerable
attention in photocatalytic applications due to synergistic effects in complex
redox processes. The incorporation of solid solutions into such architectures can
further offer extra variability to control the bandgap. In this study, we report
the fabrication of a series of core-shell Cd0.2Zn0.8S@BiOX (X = Cl, Br and I)
microspheres via a solvothermal route that lead to enhanced photocatalytic
performance under visible light irradiation. By optimizing the synthesis
conditions, uniform and porous Cd0.2Zn0.8S@BiOX microspheres were achieved. The
products were thoroughly characterized by X-ray diffraction studies, scanning
electron microscopy, transmission electron microscopy, photoluminescence studies,
absorption measurements and the photodegradation of RhB. Remarkably, the
electronic structures of Cd0.2Zn0.8S@BiOX composites can be continuously tuned by
varying the composition of BiOX to achieve the best catalytic performance under
visible light irradiation. Finally, this greatly enhanced visible-light-driven
photocatalytic efficiency was observed in the optimized Cd0.2Zn0.8S@BiOI
composites when compared to their single-component counterparts, which may be
attributed to increased light absorption and improved electron-hole separation.
The photocatalytic mechanism has also been proposed based on the experimental
evidences and the theoretical band positions of Cd0.2Zn0.8S@BiOI.
PMID- 27510185
TI - Long-term chemotherapy-induced peripheral neuropathy among breast cancer
survivors: prevalence, risk factors, and fall risk.
AB - Chemotherapy-induced peripheral neuropathy (CIPN) is a common toxicity associated
with chemotherapy, but researchers rarely study its risk factors, fall risk, and
prevalence in long-term breast cancer survivors. We aimed to determine CIPN
prevalence, risk factors, and association with psychological distress and falls
among long-term breast cancer survivors. We conducted Cross-sectional analyses
among postmenopausal women with a history of stage I-III breast cancer who
received taxane-based chemotherapy. Participants reported neuropathic symptoms of
tingling/numbness in hands and/or feet on a 0-10 numerical rating scale. We
conducted multivariate logistic regression analyses to evaluate risk factors
associated with the presence of CIPN and the relationship between CIPN and
anxiety, depression, insomnia, and patient-reported falls. Among 296
participants, 173 (58.4 %) reported CIPN symptoms, 91 (30.7 %) rated their
symptoms as mild, and 82 (27.7 %) rated them moderate to severe. Compared with
women of normal weight, being obese was associated with increased risk of CIPN
(adjusted OR 1.94, 95 % CI: 1.03-3.65). Patients with CIPN reported greater
insomnia severity, anxiety, and depression than those without (all p < 0.05).
Severity of CIPN was associated with higher rates of falls, with 23.8, 31.9, and
41.5 % in the "no CIPN," "mild," and "moderate-to-severe" groups, respectively,
experiencing falls (p = 0.028). The majority of long-term breast cancer survivors
who received taxane-based chemotherapy reported CIPN symptoms; obesity was a
significant risk factor. Those with CIPN also reported increased psychological
distress and falls. Interventions need to target CIPN and comorbid psychological
symptoms, and incorporate fall prevention strategies for aging breast cancer
survivors.
PMID- 27510187
TI - Physicists need to make the case for high-energy experiments.
PMID- 27510186
TI - Lifetime grain consumption and breast cancer risk.
AB - We evaluated individual grain-containing foods and whole and refined grain intake
during adolescence, early adulthood, and premenopausal years in relation to
breast cancer risk in the Nurses' Health Study II. Grain-containing food intakes
were reported on a baseline dietary questionnaire (1991) and every 4 years
thereafter. Among 90,516 premenopausal women aged 27-44 years, we prospectively
identified 3235 invasive breast cancer cases during follow-up to 2013. 44,263
women reported their diet during high school, and from 1998 to 2013, 1347 breast
cancer cases were identified among these women. Cox proportional hazards
regression was used to estimate relative risks (RR) and 95 % confidence intervals
(95 % CI) of breast cancer for individual, whole and refined grain foods. After
adjusting for known breast cancer risk factors, adult intake of whole grain foods
was associated with lower premenopausal breast cancer risk (highest vs. lowest
quintile: RR 0.82; 95 % CI 0.70-0.97; P trend = 0.03), but not postmenopausal
breast cancer. This association was no longer significant after further
adjustment for fiber intake. The average of adolescent and early adulthood whole
grain food intake was suggestively associated with lower premenopausal breast
cancer risk (highest vs lowest quintile: RR 0.74; 95 % CI 0.56-0.99; P trend =
0.09). Total refined grain food intake was not associated with risk of breast
cancer. Most individual grain-containing foods were not associated with breast
cancer risk. The exceptions were adult brown rice which was associated with lower
risk of overall and premenopausal breast cancer (for each 2 servings/week: RR
0.94; 95 % CI 0.89-0.99 and RR 0.91; 95 % CI 0.85-0.99, respectively) and adult
white bread intake which was associated with increased overall breast cancer risk
(for each 2 servings/week: RR 1.02; 95 % CI 1.01-1.04), as well as breast cancer
before and after menopause. Further, pasta intake was inversely associated with
overall breast cancer risk. Our results suggest that high whole grain food intake
may be associated with lower breast cancer risk before menopause. Fiber in whole
grain foods may mediate the association with whole grains.
PMID- 27510188
TI - A safe place for nuclear energy?
PMID- 27510189
TI - Steer driverless cars towards full automation.
PMID- 27510200
TI - Hopes for revolutionary new LHC particle dashed.
PMID- 27510201
TI - Glider aims to break world record--and boost climate science.
PMID- 27510202
TI - US agency to lift ban on funding human-animal hybrids.
PMID- 27510204
TI - Replications, ridicule and a recluse: the controversy over NgAgo gene-editing
intensifies.
PMID- 27510203
TI - Beyond CRISPR: A guide to the many other ways to edit a genome.
PMID- 27510205
TI - Plant and animal DNA suggests first Americans took the coastal route.
PMID- 27510206
TI - The bandwidth bottleneck that is throttling the Internet.
PMID- 27510207
TI - Biodiversity: The ravages of guns, nets and bulldozers.
PMID- 27510210
TI - Education: Reforms set to seep into India's schools.
PMID- 27510211
TI - Weather communications: Satellite company clarifies proposal.
PMID- 27510212
TI - Funding: Would Mendel have won it?
PMID- 27510213
TI - Funding: Spot value in grant proposals.
PMID- 27510214
TI - Profiles: Kudos for female Antarctic researchers.
PMID- 27510215
TI - Energy science: Fast track for silver.
PMID- 27510217
TI - Synergistic, ultrafast mass storage and removal in artificial mixed conductors.
AB - Mixed conductors-single phases that conduct electronically and ionically-enable
stoichiometric variations in a material and, therefore, mass storage and
redistribution, for example, in battery electrodes. We have considered how such
properties may be achieved synergistically in solid two-phase systems, forming
artificial mixed conductors. Previously investigated composites suffered from
poor kinetics and did not allow for a clear determination of such stoichiometric
variations. Here we show, using electrochemical and chemical methods, that a melt
processed composite of the 'super-ionic' conductor RbAg4I5 and the electronic
conductor graphite exhibits both a remarkable silver excess and a silver
deficiency, similar to those found in single-phase mixed conductors, even though
such behaviour is not possible in the individual phases. Furthermore, the
kinetics of silver uptake and release is very fast. Evaluating the upper limit of
the relaxation time [corrected] set by interfacial ambipolar diffusion reveals
chemical diffusion coefficients that are even higher than those achieved for
sodium chloride in bulk liquid water. These results could potentially stimulate
systematic research into powerful, even mesoscopic, artificial mixed conductors.
PMID- 27510220
TI - Assessing agricultural drought in summer over Oklahoma Mesonet sites using the
water-related vegetation index from MODIS.
AB - Agricultural drought, a common phenomenon in most parts of the world, is one of
the most challenging natural hazards to monitor effectively. Land surface water
index (LSWI), calculated as a normalized ratio between near infrared (NIR) and
short-wave infrared (SWIR), is sensitive to vegetation and soil water content.
This study examined the potential of a LSWI-based, drought-monitoring algorithm
to assess summer drought over 113 Oklahoma Mesonet stations comprising various
land cover and soil types in Oklahoma. Drought duration in a year was determined
by the number of days with LSWI <0 (DNLSWI) during summer months (June-August).
Summer rainfall anomalies and LSWI anomalies followed a similar seasonal dynamics
and showed strong correlations (r 2 = 0.62-0.73) during drought years (2001,
2006, 2011, and 2012). The DNLSWI tracked the east-west gradient of summer
rainfall in Oklahoma. Drought intensity increased with increasing duration of
DNLSWI, and the intensity increased rapidly when DNLSWI was more than 48 days.
The comparison between LSWI and the US Drought Monitor (USDM) showed a strong
linear negative relationship; i.e., higher drought intensity tends to have lower
LSWI values and vice versa. However, the agreement between LSWI-based algorithm
and USDM indicators varied substantially from 32 % (D 2 class, moderate drought)
to 77 % (0 and D 0 class, no drought) for different drought intensity classes and
varied from ~30 % (western Oklahoma) to >80 % (eastern Oklahoma) across regions.
Our results illustrated that drought intensity thresholds can be established by
counting DNLSWI (in days) and used as a simple complementary tool in several
drought applications for semi-arid and semi-humid regions of Oklahoma. However,
larger discrepancies between USDM and the LSWI-based algorithm in arid regions of
western Oklahoma suggest the requirement of further adjustment in the algorithm
for its application in arid regions.
PMID- 27510221
TI - Impact of the Molecular Environment on Thiol-Ene Coupling For
Biofunctionalization and Conjugation.
AB - Thiol-ene radical coupling is increasingly used for the biofunctionalization of
biomaterials and the formation of 3D hydrogels enabling cell encapsulation.
Indeed, thiol-ene chemistry presents interesting features that are particularly
attractive for platforms requiring specific reactions of peptides or proteins, in
particular, in situ, during cell culture or encapsulation. Despite such interest,
little is known about the factors impacting thiol-ene chemistry in situ, under
biologically relevant conditions. Here we explore some of the molecular
parameters controlling photoinitiated thiol-ene couplings with a series of
alkenes and thiols, including peptides, in buffered conditions. (1)H NMR and HPLC
were used to quantify the efficiency of couplings and the impact of the pH of the
buffer, as well as the molecular structure and local microenvironment close to
alkenes and thiols to be coupled. Some of these observations are supported by
molecular dynamics and quantum mechanics calculations. An important finding of
our work is that the pKa of thiols (and its variation upon changes in molecular
structure) have a striking impact on coupling efficiencies. Similarly, positively
charged and aromatic amino acids are found to have some impact on thiol-ene
couplings. Hence, our study demonstrates that molecular design should be
carefully selected in order to achieve high biofunctionalization levels in
biomaterials with peptides or promote the efficient formation of peptide-based
hydrogels.
PMID- 27510219
TI - Mapping B-cell responses to Salmonella enterica serovars Typhimurium and
Enteritidis in chickens for the discrimination of infected from vaccinated
animals.
AB - Serological surveillance and vaccination are important strategies for controlling
infectious diseases of food production animals. However, the compatibility of
these strategies is limited by a lack of assays capable of differentiating
infected from vaccinated animals (DIVA tests) for established killed or
attenuated vaccines. Here, we used next generation phage-display (NGPD) and a 2
proportion Z score analysis to identify peptides that were preferentially bound
by IgY from chickens infected with Salmonella Typhimurium or S. Enteritidis
compared to IgY from vaccinates, for both an attenuated and an inactivated
commercial vaccine. Peptides that were highly enriched against IgY from at least
4 out of 10 infected chickens were selected: 18 and 12 peptides for the killed
and attenuated vaccines, respectively. The ten most discriminatory peptides for
each vaccine were identified in an ELISA using a training set of IgY samples.
These peptides were then used in multi-peptide assays that, when analysing a
wider set of samples from infected and vaccinated animals, diagnosed infection
with 100% sensitivity and specificity. The data describes a method for the
development of DIVA assays for conventional attenuated and killed vaccines.
PMID- 27510223
TI - Integrative analysis of human omics data using biomolecular networks.
AB - High-throughput '-omics' technologies have given rise to an increasing abundance
of genome-scale data detailing human biology at the molecular level. Although
these datasets have already made substantial contributions to a more
comprehensive understanding of human physiology and diseases, their
interpretation becomes increasingly cryptic and nontrivial as they continue to
expand in size and complexity. Systems biology networks offer a scaffold upon
which omics data can be integrated, facilitating the extraction of new and
physiologically relevant information from the data. Two of the most prevalent
networks that have been used for such integrative analyses of omics data are
genome-scale metabolic models (GEMs) and protein-protein interaction (PPI)
networks, both of which have demonstrated success among many different omics and
sample types. This integrative approach seeks to unite 'top-down' omics data with
'bottom-up' biological networks in a synergistic fashion that draws on the
strengths of both strategies. As the volume and resolution of high-throughput
omics data continue to grow, integrative network-based analyses are expected to
play an increasingly important role in their interpretation.
PMID- 27510222
TI - Single and multi-subject clustering of flow cytometry data for cell-type
identification and anomaly detection.
AB - BACKGROUND: Measurement of various markers of single cells using flow cytometry
has several biological applications. These applications include improving our
understanding of behavior of cellular systems, identifying rare cell populations
and personalized medication. A common critical issue in the existing methods is
identification of the number of cellular populations which heavily affects the
accuracy of results. Furthermore, anomaly detection is crucial in flow cytometry
experiments. In this work, we propose a two-stage clustering technique for cell
type identification in single subject flow cytometry data and extend it for
anomaly detection among multiple subjects. RESULTS: Our experimentation on 42
flow cytometry datasets indicates high performance and accurate clustering (F
measure > 91 %) in identifying main cellular populations. Furthermore, our
anomaly detection technique evaluated on Acute Myeloid Leukemia dataset results
in only <2 % false positives.
PMID- 27510224
TI - Paediatric heart sound signal analysis towards classification using multifractal
spectra.
AB - Healthy versus unhealthy heart sound computer-aided classification tools are very
popular for supporting clinical decisions. In this paper a new method is proposed
for the classification of heart sound recordings from a statistical standpoint
without detection and localization of fundamental heart sounds (S1, S2). This
study analyzes the possibility of detecting healthy heart sound signal from a
large set of measurements, corresponding to different pathologies, such as aortic
regurgitation, mitral regurgitation, aortic stenosis and ventricular septal
defects. The proposed method employs singularity spectra analysis and long-term
dependency of irregular structures. Healthy signals are firstly separated from
the rest of the recordings. In the second step, the signals with a click
syndrome, used here as a reference, are detected in the unhealthy group. Innocent
murmurs have not been considered in this paper. Each auscultatory recording is
classified into one of the following classes: healthy; click syndrome; and other
heart dysfunctions. The results of the proposed method provided high recall and
precision values for each of the three classes. Since the presence of additive
noise may affect the classification, we also analyzed the possibility of
classifying signals in such circumstances. The method was tested, verified and
showed high accuracy.
PMID- 27510226
TI - Renal replacement therapy during Stevens-Johnson syndrome and toxic epidermal
necrolysis: a retrospective observational study of 238 patients.
PMID- 27510225
TI - Dietary and microbiome factors determine longevity in Caenorhabditis elegans.
AB - Diet composition affects organismal health. Nutrient uptake depends on the
microbiome. Caenorhabditis elegans fed a Bacillus subtilis diet live longer than
those fed the standard Escherichia coli diet. Here we report that this longevity
difference is primarily caused by dietary coQ, an antioxidant synthesized by E.
coli but not by B. subtilis. CoQ-supplemented E. coli fed worms have a lower
oxidation state yet live shorter than coQ-less B. subtilis fed worms. We showed
that mutations affecting longevity for E. coli fed worms do not always lead to
similar effects when worms are fed B. subtilis. We propose that coQ
supplementation by the E. coli diet alters the worm cellular REDOX homeostasis,
thus decreasing longevity. Our results highlight the importance of microbiome
factors in longevity, argue that antioxidant supplementation can be detrimental,
and suggest that the C. elegans standard E. coli diet can alter the effect of
signaling pathways on longevity.
PMID- 27510227
TI - [Preoperative auditory evaluation and postoperative follow-up in cochlear
implantees : The role of objective measures].
AB - The primary diagnostic aim prior to cochlear implantation is establishment of a
comprehensive and multidisciplinary diagnosis, in order to subsequently begin
therapy as early as possible. Audiological evaluation prior to implantation
employs a test battery-approach, including subjective and objective procedures.
Objective measures show high reliability and therefore play a major role in the
diagnosis of difficult-to-test subjects such as infants and young children.
During postoperative follow-up, objective measures offer a valid method for
analyzing the effects of different stimuli on the auditory system. Particularly
in infants, children, and uncooperative patients, the results of these tests
enable the speech processor settings to be optimized, the hearing benefit to be
assessed, and treatment to be adapted accordingly. Auditory brainstem responses
(ABR) offer an excellent test/retest and inter-/intrarater reliability and
validity, and are the most commonly used method for objective hearing threshold
estimation and evaluation of the functional integrity of the lower auditory
pathway. The use of narrow-band stimuli allows frequency-specific threshold
estimation; analysis of stationary auditory steady state potentials (ASSR) adds
the advantages of automated objective detection. Electrocochleography and
electrically evoked ABR give valuable information in special cases. The use of
cortical potentials (CAEP) in response to speech stimuli is quite promising,
although the high response variability currently limits this method's clinical
application. An audiological test-battery approach combining the results of
subjective and objective measures leads to significantly increased reliability of
preoperative diagnosis and postoperative follow-up in cochlear implantees.
PMID- 27510228
TI - [Robot-assisted surgery in the head and neck region].
AB - Robot-assisted surgery (RAS) in the head and neck region is believed to have a
large potential for the improvement of patient care. Several systems with a
master-slave setup are already in routine clinical use, particularly for
oncologic surgery. Although specific patient groups may benefit from RAS, there
is a lack of randomized clinical studies validating the advantages of these new
technological systems in comparison to the existing standard procedures. On the
other hand, RAS in the head and neck region is being constantly developed.
Currently, the main limitations are the technical miniaturization of the tools
and the loss of haptic feedback, as well as the high costs for acquisition and
maintenance without financial reimbursement. In any case, the current generation
of head and neck surgeons will face the technical, scientific, and ethical
challenges of RAS.
PMID- 27510229
TI - Effect of Left Atrial Wall Thickness on Radiofrequency Ablation Success.
AB - INTRODUCTION: Radiofrequency (RF) ablation in thicker regions of the left atrium
(LA) may require increased ablation energy in order to achieve effective
transmural lesions. Consequently, many cases of recurrent atrial fibrillation
(AF) postablation may be due to thicker-than-normal atrial tissue. The aim of
this study was to test the hypotheses that patients with recurrent AF have
thicker tissue overall and that electrical reconnection is more likely in regions
of thicker tissue. METHODS AND RESULTS: Retrospective analysis was performed on
86 CT images acquired preoperatively from a cohort of 119 patients who had
undergone RF ablation for AF. Of these, 33 patients experienced recurrence of AF
within 1 year of initial treatment and 29 returned for a repeat ablation. For
each patient, LA wall thickness (LAWT) was measured from the images in 12
anatomical regions using custom software. Patients with recurrent AF had larger
LAWT compared to successfully treated patients (1.6 +/- 0.6 mm vs. 1.5 +/- 0.5
mm, P < 0.001) and reconnection was found to be at regions of thicker tissue (1.6
+/- 0.6 mm, P = 0.038) compared to nonreconnected regions (1.5 +/- 0.5 mm). The
superior right posterior wall of the LA was significantly related to both
recurrence (P = 0.048) and reconnection (P = 0.014). CONCLUSION: Increased LAWT
has a small but significant effect on postablation recurrence and reconnection.
Measures of LAWT may facilitate appropriate dosing of RF energy, but other
factors will be critical in transmural lesion formation and ablation success.
PMID- 27510231
TI - Retrospective assessment of childhood ADHD symptoms for diagnosis in adults:
validity of a short 8-item version of the Wender-Utah Rating Scale.
AB - The Wender-Utah Rating Scale (WURS) is a widely used self-report instrument for
retrospective assessment of childhood ADHD. However, many WURS items are not
specific to ADHD. Here, we investigated the effect of excluding these items on
the performance of the WURS in predicting adult ADHD based on previous diagnosis
and current clinically significant symptoms. The study was conducted on a sample
of adults (n = 1014; 48 % male) participating in a family-based investigation of
ADHD. Participants completed the 61-item WURS questionnaire and the 66-item
Conners Adult ADHD Rating Scale. Receiver operating characteristic (ROC) curves
were used to compare the performance of the eight-item WURS (WURS-8) and the
longer WURS-25 in predicting previous ADHD diagnosis and current clinically
significant ADHD symptoms. WURS-8 and WURS-25 have approximately the same power
to predict adult ADHD, based on either previous diagnosis or current symptoms
(area under the ROC curves >0.8). WURS-8 performs at least as well as the longer
WURS-25 in predicting adult ADHD. This 8-item questionnaire is thus a valid
instrument and is especially useful for screening for ADHD in large
epidemiological samples.
PMID- 27510232
TI - Simple and practical measures to reduce tuberculosis transmission in public
buildings.
PMID- 27510230
TI - Targeting multiple oncogenic pathways for the treatment of hepatocellular
carcinoma.
AB - Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer
diagnosed worldwide. HCC occurs due to chronic liver disease and is often
diagnosed at advanced stages. Chemotherapeutic agents such as doxorubicin are
currently used as first-line agents for HCC therapy, but these are non-selective
cytotoxic molecules with significant side effects. Sorafenib, a multi-targeted
tyrosine kinase inhibitor, is the only approved targeted drug for HCC patients.
However, due to adverse side effects and limited efficacy, there is a need for
the identification of novel pharmacological drugs beyond sorafenib. Several
agents that target and inhibit various signaling pathways involved in HCC are
currently being assessed for HCC treatment. In the present review article, we
summarize the diverse signal transduction pathways responsible for initiation as
well as progression of HCC and also the potential anticancer effects of selected
targeted therapies that can be employed for HCC therapy.
PMID- 27510233
TI - Occupational exposure to tuberculosis in endemic areas: room for improvement.
PMID- 27510234
TI - Isolation is not everything.
PMID- 27510235
TI - Why patient-centered care matters.
PMID- 27510236
TI - Implementing a spirometry program.
PMID- 27510237
TI - Gatifloxacin for short, effective treatment of multidrug-resistant tuberculosis.
AB - The 9-month regimen for the treatment of multidrug-resistant tuberculosis (MDR
TB) piloted in Bangladesh and used, with modifications, in Cameroon and Niger,
has achieved treatment success in a very large proportion of patients;
gatifloxacin (GFX) is likely to have played a critical role in this success. Two
months after the publication of a study reporting that GFX and not moxifloxacin
(MFX) was associated with dysglycaemia, the manufacturer announced the withdrawal
of GFX from the market. The findings of that study may have less significance for
the majority of MDR-TB patients living in high-incidence countries who are much
younger, have a lower risk of dysglycaemia and suffer from a highly fatal
condition. The problem of dysglycaemia is not limited to GFX use and may occur
with other fluoroquinolones; furthermore, GFX-associated dysglycemia was
manageable among those MDR-TB patients in Bangladesh and Niger in whom it
occurred. GFX has now become unavailable in Bangladesh, Cameroon, Niger and other
countries piloting the shorter MDR-TB regimens, depriving resource-poor countries
of an efficacious, effective and inexpensive drug with a demonstrated good safety
profile for the given indication. There is little reason not to make GFX
available for MDR-TB treatment as long as the superiority of non-GFX-based MDR-TB
regimens is not demonstrated.
PMID- 27510238
TI - Ending tuberculosis by 2030: can we do it?
AB - The Sustainable Development Goals aim to end tuberculosis (TB) related deaths,
transmission and catastrophic costs by 2030. Multisectorial action to accelerate
socio-economic development, a new vaccine and novel diagnostics and medicines for
treatment are key advances needed to end TB transmission. Achieving 90-90-90
targets for TB (i.e., 90% of vulnerable populations screened, 90% diagnosed and
started on treatment, and at least 90% cured) will help accelerate progress
towards reductions in mortality; however, passive case detection strategies,
multidrug-resistant TB, human immunodeficiency virus coinfection and outdated
pathways to care need to be overcome. Ending the catastrophic costs associated
with TB will require expansion of health insurance coverage, comprehensive
coverage of TB services, and limited indirect costs by vulnerable and poor
populations.
PMID- 27510239
TI - Measuring ventilation and modelling M. tuberculosis transmission in indoor
congregate settings, rural KwaZulu-Natal.
AB - SETTING: Molecular epidemiology suggests that most Mycobacterium tuberculosis
transmission in high-burden settings occurs outside the home. OBJECTIVE: To
estimate the risk of M. tuberculosis transmission inside public buildings in a
high TB burden community in KwaZulu-Natal, South Africa. DESIGN: Carbon dioxide
(CO2) sensors were placed inside eight public buildings. Measurements were used
with observations of occupancy to estimate infection risk using an adaptation of
the Wells-Riley equation. Ventilation modelling using CONTAM was used to examine
the impact of low-cost retrofits on transmission in a health clinic. RESULTS:
Measurements indicate that infection risk in the church, classroom and clinic
waiting room would be high with typical ventilation, occupancy levels and visit
durations. For example, we estimated that health care workers in a clinic waiting
room had a 16.9-24.5% annual risk of M. tuberculosis infection. Modelling results
indicate that the simple addition of two new windows allowing for cross
ventilation, at a cost of US$330, would reduce the annual risk to health care
workers by 57%. CONCLUSIONS: Results indicate that public buildings in this
community have a range of ventilation and occupancy characteristics that may
influence transmission risks. Simple retrofits may result in dramatic reductions
in M. tuberculosis transmission, and intervention studies should therefore be
considered.
PMID- 27510240
TI - Occupational exposure and tuberculosis among medical residents in a high-burden
setting: an open-cohort study.
AB - SETTING: Postgraduate (PG) residency programme of a tertiary care teaching
hospital in southern India. OBJECTIVE: To estimate the incidence of tuberculosis
(TB) among PG residents, determine the frequency of exposure to infectious TB
patients and assess whether particular specialties were associated with higher
risk of exposure and incident TB. DESIGN: We assembled an open cohort of PG
residents who were on the academic rolls for more than 3 months at any time
between December 2011 and January 2013. We collected data both retrospectively
and prospectively using two surveys-an entry survey at study initiation or entry
into the cohort, and an exit survey at residency completion or study closure.
RESULTS: Among 398 PG residents enrolled in the study, we identified five cases
of incident TB during a cumulative follow-up period of 10 962 person-months. The
incidence rate was 547 per 100 000 person-years, which was 3.1 times the
incidence in the general population. Nearly two thirds (n = 257, 65%) of the
residents were exposed to at least one infectious patient. Across the three
specialty-based risk strata, there was an ordered increase in the median number
of exposures (P < 0.001) and evaluation for presumptive TB (P = 0.024), as well
as a trend towards higher incident TB. CONCLUSION: TB incidence is significantly
higher among PG residents than in the general population.
PMID- 27510241
TI - Errors in isolation of patients with infectious tuberculosis at a public teaching
hospital in New York.
AB - BACKGROUND: Studies report variability in the rates and causes of isolation
errors among in-patients with active tuberculosis (TB). We reviewed our
experience with delays or premature discontinuation of airborne infection
isolation (AII). METHODS: Medical records of patients admitted to the Bellevue
Hospital Center, New York City Health & Hospitals, New York, NY, USA, between
January 2006 and July 2012 with a positive respiratory culture for Mycobacterium
tuberculosis were reviewed. Patients who were out of AII despite being infectious
were identified, as the episodes had prompted a contact investigation. RESULTS:
Of 246 admissions with positive respiratory cultures, 35 AII errors were
identified among 27 patients. Most patients had signs or symptoms of TB on
admission. Only four patients had positive sputum smears. In 16 (46%) episodes,
the patients had never been isolated, 11 (31%) had delayed isolation, and 8 (23%)
were prematurely taken off AII. The most common reasons for patients being off
AII while infectious were an incorrect alternative diagnosis (15/35, 43%) or a
dual diagnosis (9/35, 26%). CONCLUSIONS: Particularly in smear-negative cases,
AII errors due to TB may occur when providers conclude that another diagnosis
explains their findings. In many cases, that diagnosis is correct, but TB is also
present. This error rate might be a useful quality indicator.
PMID- 27510242
TI - Measurement of levels of fractional exhaled nitric oxide in patients with
pulmonary tuberculosis.
AB - SETTING: The role of fractional exhaled nitric oxide (FeNO) in the diagnosis and
treatment of pulmonary tuberculosis (PTB) is uncertain. OBJECTIVE: To examine the
value of FeNO as a biomarker for PTB. DESIGN: Baseline FeNO levels were compared
in 69 PTB patients and 118 healthy controls. The correlation between baseline
FeNO levels and clinical variables of tuberculosis were studied. FeNO levels were
checked twice in the PTB group, at diagnosis and after 2 months of anti
tuberculosis medication, and factors affecting changes in FeNO levels after
treatment were analysed. RESULTS: FeNO levels were not significantly different in
the PTB group and controls (mean +/- standard deviation 27.7 +/- 17.6 parts per
billion [ppb] vs. 27.0 +/- 10.8 ppb, P = 0.531). In a multivariate regression
analysis, no variable was shown to affect FeNO levels at diagnosis. FeNO levels
did not significantly change after 2 months of treatment (26.8 +/- 18.3 ppb vs.
24.0 +/- 10.7 ppb, P = 0.257). Only PTB with a high FeNO level (>25 ppb) was
related to a decline in FeNO levels after 2 months of treatment. CONCLUSION: FeNO
levels do not appear to be affected in PTB patients.
PMID- 27510243
TI - Improved tuberculosis outcomes with daily vs. intermittent rifabutin in HIV-TB
coinfected patients in India.
AB - SETTING: Y R Gaitonde Centre for AIDS Research and Education, Chennai, India.
OBJECTIVE: To compare anti-tuberculosis treatment outcomes in individuals with
human immunodeficiency virus (HIV) and tuberculosis (TB) co-infection on
atazanavir/ritonavir (ATV/r) antiretroviral therapy (ART) plus daily rifabutin
(RBT) 150 mg with those on ATV/r plus thrice-weekly RBT 150 mg. DESIGN: A
retrospective study was conducted of two HIV-TB co-infected cohorts between 2003
and 2014. Basic demographic and TB outcome data were obtained from an electronic
database and patient records. The chi(2) and Fisher's exact test were used to
compare daily and intermittent RBT treatment groups. RESULTS: Of 292 individuals
on an ATV/r-based ART regimen plus RBT, 118 (40.4%) received thrice-weekly RBT
and 174 (59.6%) daily RBT. Patients in the two RBT treatment groups were similar
in sex, age, previous history of TB, site of TB and acid-fast bacilli smear
status. More individuals in the daily vs. the intermittent RBT group achieved
clinical cure (73.0% vs. 44.1%, P < 0.001), with no significant differences in
relapse/recurrence or all-cause mortality between groups. CONCLUSION: There were
higher rates of clinical TB cure in individuals on a boosted protease inhibitor
based ART regimen with daily RBT compared to intermittently dosed RBT. Optimal
RBT dosing in this setting requires further investigation.
PMID- 27510244
TI - An integrated community TB-HIV adherence model provides an alternative to DOT for
tuberculosis patients in Cape Town.
AB - SETTING: Cape Town, South Africa. OBJECTIVE: To evaluate anti-tuberculosis
treatment outcomes and rate of antiretroviral therapy (ART) initiation using
weekly community-based adherence support compared to daily directly observed
therapy (DOT). METHODS: This was a retrospective analysis comparing two cohorts
treated for tuberculosis (TB) in 70 TB clinics during 6-month periods before and
after the introduction of a new adherence model comprising treatment literacy
sessions during 2 weeks of DOT, followed by weekly home visits by community care
workers to eligible patients managing their own treatment. Odds ratios (ORs) of
treatment success and ART initiation were calculated using multivariable random
effects logistic regression models. Hazard ratios (HRs) of default and death were
calculated using multivariable random effects Cox regression models. RESULTS: The
pre-intervention cohort comprised 11 896 patients with TB and the post
intervention cohort 11 314. There was no difference in pre- and post-intervention
anti-tuberculosis treatment success rates (respectively 82.8% and 82.5%, adjusted
OR [aOR] 1.02, 95%CI 0.89-1.17, P = 0.76) nor an increased hazard of death
(adjusted HR [aHR] 0.98, 95%CI 0.80-1.21, P = 0.87) or default (aHR 0.97, 95%CI
0.81-1.15, P = 0.69). The ART initiation rate increased from 67% to 74% (aOR
1.43; 95%CI 1.01-1.85, P < 0.01). CONCLUSION: Weekly community-based adherence
support was a viable alternative to daily DOT, with no deterioration in anti
tuberculosis treatment outcomes and an increase in ART initiation.
PMID- 27510245
TI - Trends in tuberculosis case notification and treatment outcomes after
interventions in 10 zones of Ethiopia.
AB - SETTING: Amhara and Oromia Regions, Ethiopia. OBJECTIVE: To determine trends in
case notification rates (CNRs) among new tuberculosis (TB) cases and treatment
outcomes of sputum smear-positive (SS+) patients based on geographic setting, sex
and age categories. METHODS: We undertook a trend analysis over a 4-year period
among new TB cases reported in 10 zones using a trend test, a mean comparison t
test and one-way analysis of variance. RESULTS: The average CNR per 100 000
population was 128.9: 126.4 in Amhara and 131.4 in Oromia. The CNR in the project
supported zones declined annually by 6.5%, compared with a 14.5% decline in
Tigray, the comparator region. TB notification in the intervention zones
contributed 26.1% of the national TB case notification, compared to 13.3% before
project intervention. The overall male-to-female ratio was 1.2, compared to 0.8
among SS+ children, with a female preponderance. Over 4 years, the cure rate
increased from 75% to 88.4%, and treatment success from 89% to 93%. Default,
transfer out and mortality rates declined significantly. CONCLUSION: Project
supported zones had lower rates of decline in TB case notification than the
comparator region; their contribution to national case finding increased, and
treatment outcomes improved significantly. High SS+ rates among girls deserve
attention.
PMID- 27510246
TI - Community knowledge, attitudes and practices in relation to tuberculosis in
Cameroon.
AB - SETTING: With 15 080 new cases in 2013, Cameroon is a country with high
tuberculosis (TB) incidence and prevalence. Understanding the community's
knowledge, attitude and practice (KAP) about TB is key to TB control in such
endemic settings. OBJECTIVES: To assess TB-related KAP in Cameroon by describing
the sociodemographics of respondents, to identify barriers to seeking care and to
explore attitudes and experiences of stigma and discrimination related to TB in
communities. DESIGN: We conducted a cross-sectional descriptive study using
structured questionnaires to assess and compare TB KAP in the entire territory.
RESULTS: The results showed that Cameroonians have insufficient understanding of
TB, numerous erroneous health assumptions and beliefs concerning TB, and
erroneous information about the symptoms and mode of transmission of the disease.
CONCLUSION: Negative attitudes and poor practices are obstacles to elimination
and control efforts. The National Tuberculosis Control Programme should generate
more effective strategies to reach the populations, paying particular attention
to rural populations.
PMID- 27510247
TI - Multidrug-resistant tuberculosis patients lost to follow-up: self-reported
readiness to restart treatment.
AB - SETTING: Multidrug-resistant tuberculosis (MDR-TB) patients lost to follow-up
(LTFU) from Programmatic Management of Drug-resistant Tuberculosis facilities in
the Philippines. OBJECTIVES: To gain insight into patients' readiness to return
to treatment. METHODS: MDR-TB patients who initiated treatment and were
categorized as LTFU were identified using TB registers, contacted, and asked to
consent to an interview and medical record review. At the conclusion of the
interview, patients' readiness to restart treatment was assessed and examined in
relation to demographic, clinical, and interview data. Odds ratios were
calculated. RESULTS: When asked if they would consider restarting MDR-TB
treatment, 3% of the 89 participating patients reported that they had already
restarted, 34% indicated that they wanted to restart, 33% had not considered
restarting, 28% were undecided, and 2% had decided against restarting. Patients
who wanted to restart treatment were more likely to report having borrowed money
for TB-related expenses (OR 5.97, 95%CI 1.27-28.18), and were less likely to
report being self-employed (OR 0.08, 95%CI 0.01-0.67), or perceive themselves at
low or no risk for TB relapse (OR 0.30, 95%CI 0.08-0.96) than patients who did
not indicate an interest in restarting treatment. CONCLUSIONS: Efforts to re
engage LTFU patients in care should consider financial barriers, knowledge gaps,
and personal adherence challenges in patients.
PMID- 27510248
TI - Higher cost of implementing Xpert((r)) MTB/RIF in Ugandan peripheral settings:
implications for cost-effectiveness.
AB - SETTING: Initial cost-effectiveness evaluations of Xpert((r)) MTB/RIF for
tuberculosis (TB) diagnosis have not fully accounted for the realities of
implementation in peripheral settings. OBJECTIVE: To evaluate costs and
diagnostic outcomes of Xpert testing implemented at various health care levels in
Uganda. DESIGN: We collected empirical cost data from five health centers
utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed
laboratory and patient records to assess outcomes at these sites and10 sites
without Xpert. We also estimated incremental cost-effectiveness of Xpert testing;
our primary outcome was the incremental cost of Xpert testing per newly detected
TB case. RESULTS: The mean unit cost of an Xpert test was US$21 based on a mean
monthly volume of 54 tests per site, although unit cost varied widely (US$16-58)
and was primarily determined by testing volume. Total diagnostic costs were 2.4
fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only
increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per
newly detected TB case, but were as high as US$885 at the center with the lowest
volume of tests. CONCLUSION: Xpert testing can detect TB cases at reasonable
cost, but may double diagnostic budgets for relatively small gains, with cost
effectiveness deteriorating with lower testing volumes.
PMID- 27510249
TI - Modelling the time to detection of urban tuberculosis in two big cities in
Portugal: a spatial survival analysis.
AB - SETTING: Portuguese National Tuberculosis Control Programme. OBJECTIVE: To
examine delays in tuberculosis (TB) diagnosis using a spatial component in two
high-incidence cities, Lisbon and Oporto, in Portugal, a low-incidence country.
DESIGN: A retrospective nationwide study was conducted based on official TB data
between 2010 and 2013 to analyse diagnostic delays at the lowest administrative
level (freguesias) using spatial survival analyses, taking into account
individual level covariates. RESULTS: Median diagnostic delays in Lisbon (n =
2706 cases) and Oporto (n = 1883) were respectively 62 (range 1-359, mean 81.01)
and 60 days (range 1-3544, mean 79.5). In both cities, case detection rates
initially rose until 50 days, then stabilised, but rose again at about 200 days.
Diagnostic delay was significantly shorter among males and human immunodeficiency
virus positive individuals in both cities, but was significantly longer among
migrants in Lisbon. There is evidence of spatial correlation between freguesias;
different spatial patterns were observed in diagnostic delays and in likelihood
of case detection. CONCLUSION: These results are concordant with existing
literature. The two study areas present considerable spatial variations in
diagnostic delay, highlighting the fact that large cities should not be treated
as homogeneous entities. The potential of spatial survival methods in spatial
epidemiology is highlighted.
PMID- 27510250
TI - Computer-aided detection of pulmonary tuberculosis on digital chest radiographs:
a systematic review.
AB - OBJECTIVE: To systematically review the diagnostic accuracy of computer-aided
detection (CAD) of pulmonary tuberculosis (PTB) on digital chest radiographs
(CXR). DESIGN: We searched four databases for articles published between January
2010 and December 2015 comparing CAD of PTB on CXR to a microbiologic reference
standard (smear, culture or polymerase chain reaction). We collected and
summarised data on study design, CAD software and diagnostic accuracy
(sensitivity, specificity, area under the curve [AUC]). RESULTS: We included 5 of
455 articles identified by searching databases. PTB prevalence ranged from 18% to
60%, and human immunodeficiency virus (HIV) prevalence from 33% to 68%. All
articles evaluated CAD4TB, the only commercially available software. AUC ranged
from 0.71 to 0.84. Software settings that increased sensitivity resulted in
important reductions in specificity, and vice versa. Risk of bias was low in
prospective studies (n = 2), and high in retrospective studies (n = 3).
CONCLUSION: Evidence assessing CAD's diagnostic accuracy is limited by the small
number of studies, most of which have important methodological limitations, the
availability and evaluation of only one software programme, and limited
generalisability to settings where PTB and HIV are less prevalent. Additional
research is required.
PMID- 27510251
TI - SLCO1B1 gene polymorphisms do not influence plasma rifampicin concentrations in a
South Indian population.
AB - OBJECTIVE: To determine the effect of SLCO1B1 gene polymorphisms (rs11045819,
rs4149032 and rs4149033) on rifampicin (RMP) concentrations in adult tuberculosis
(TB) patients from south India. METHODS: We genotyped adult TB patients for three
SLCO1B1 gene polymorphisms-rs11045819, rs4149032 and rs4149033-and compared 2-h
post-dosing RMP concentrations of the different genotypes for each of the
polymorphisms. Plasma RMP was determined using high-performance liquid
chromatography. Genotyping was performed using direct sequencing. RESULTS: Among
the 256 study patients, minor allele frequencies were respectively 0.01 (A), 0.46
(C) and 0.07 (A) for rs11045819, rs4149032 and rs4149033 polymorphisms; genotype
distributions followed Hardy-Weinberg equilibrium. RMP concentrations did not
significantly differ between the different genotypes of the three polymorphisms.
CONCLUSION: This is the first study to show that rs11045819, rs4149032 and
rs4149033 polymorphisms in the SLCO1B1 gene did not influence RMP concentrations
in Indian patients.
PMID- 27510252
TI - Pharmacokinetics of thrice-weekly rifampicin, isoniazid and pyrazinamide in adult
tuberculosis patients in India.
AB - OBJECTIVE: To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and
pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that
influence drug pharmacokinetics. METHODS: Adult TB patients (n = 101) receiving
thrice-weekly anti-tuberculosis treatment in the Revised National TB Control
Programme (RNTCP) were studied. The study was conducted at steady state after
directly observed drug administration. RMP, INH and PZA concentrations were
estimated using high-performance liquid chromatography and NAT2 genotyping by
real-time polymerase chain reaction. RESULTS: RMP peak concentration (Cmax) was
sub-therapeutic (<8 MUg/ml) in 88% of the patients. The Cmax of RMP, INH and PZA
at 2 h was observed in respectively 83.2%, 97.0% and 92.1% of the patients. The
Cmax and area under the curve from 0 to 8 h (AUC0-8) of PZA was lower in TB
patients with diabetes mellitus than in non-diabetics. Significant associations
were observed between the Cmax and the AUC0-8 of RMP, INH and PZA with drug
doses; RMP with category of treatment; INH with smoking, body mass index and N
acetyl transferase 2 genotype; and PZA with sex and smoking. CONCLUSIONS: Several
risk factors for drug concentration variations were identified. Two-hour post
dosing drug concentrations mimicked Cmax. A high proportion of TB patients had
RMP Cmax below the expected range, which is a matter of concern.
PMID- 27510254
TI - Surveillance provides insight into epidemiology and spectrum of culture-confirmed
mycobacterial disease in children.
AB - BACKGROUND: Longer-term tuberculosis (TB) drug resistance surveillance among
children is rare. We determined the prevalence of drug resistance among children
with culture-confirmed TB from 2011 to 2013, compared these results with four
previous consecutive 2-year periods and documented other mycobacterial isolates
identified. METHOD: Surveillance study of mycobacterial culture in all children
aged <13 years conducted from March 2011 to February 2013 at the Tygerberg
Children's Hospital, Cape Town, South Africa. Drug susceptibility testing against
isoniazid (INH) and rifampicin (RMP) was performed using line-probe assay
(GenoType((r)) MTBDRplus). Clinical data were obtained through folder review.
RESULTS: Of 381 children, 323 (84.8%; 324 episodes) had Mycobacterium
tuberculosis, 46 (12.1%) had M. bovis bacille Calmette-Guerin and 12 (3.1%) had
non-tuberculous mycobacteria isolated. Forty-one (12.7%) children had M.
tuberculosis resistant to INH and/or RMP; 15 (4.7%) had multidrug-resistant TB
(MDR-TB). The prevalence of INH mono- or polyresistance remained stable; however,
RMP monoresistance increased (0/313 in 2003-2005 vs. 6/324, 1.9%, in 2011-2013; P
= 0.041); MDR-TB prevalence has declined significantly, from 26/292 (8.9%) in
2007-2009 to 15/324 (4.7%) in 2011-2013 (OR 0.50, 95%CI 0.24-0.99). The
prevalence of human immunodeficiency virus co-infection has decreased
significantly, from a peak of 29% to 15.3%. CONCLUSIONS: There has been a
significant reduction in bacteriologically confirmed MDR-TB cases. The increase
in RMP monoresistance has important implications for treatment.
PMID- 27510253
TI - Genetic polymorphisms of CCL2 associated with susceptibility to latent
tuberculous infection in Thailand.
AB - BACKGROUND: The extent to which individuals exhibit genetic susceptibility to
tuberculosis (TB) is still unclear. Genetic variations in chemokine genes might
influence the early clearance of Mycobacterium tuberculosis, affecting TB
susceptibility. OBJECTIVES: To study single nucleotide polymorphisms (SNPs) of
chemokine genes CCL2, CXCL9, CXCL10 and CXCL11, and their association with TB
susceptibility. DESIGN: Of 248 participants enrolled, 49 had active TB, 43 had
latent tuberculous infection (LTBI) and 156 were non-infected, including 24
healthy controls with no known TB exposure. These populations were divided into
two groups based on TB exposure: susceptible (n = 92) and resistant (early
clearance) (n = 132). RESULTS: Only CCL2 SNPs (-2518A/G) were significantly
associated with increased TB susceptibility. Based on adjusted multivariate
analysis, persons with the GG genotype at this SNP were twice as susceptible to
TB as those with the AA genotype (P = 0.018, OR 2.880, 95%CI 1.201-6.903). Risk
of LTBI was three times higher among those with GG (P = 0.003, OR 3.358, 95%CI
1.525-7.396 for AA+AG vs. GG and P = 0.012, OR 3.706, 95%CI 1.340-10.254 for AA
vs. GG). Persons with the GG genotype produced significantly lower CCL2 levels in
response to M. tuberculosis antigen stimulation (AA+AG vs. GG, P = 0.038).
CONCLUSION: The CCL2 polymorphism (-2518A/G) was associated with susceptibility
to LTBI in a North-East Thai populations.
PMID- 27510255
TI - Combined approach to the identification of clinically infrequent non-tuberculous
mycobacteria in Argentina.
AB - SETTING: Over 150 potentially pathogenic non-tuberculous mycobacteria (NTM)
species have been described, posing an onerous challenge for clinical laboratory
diagnosis. OBJECTIVE: To evaluate different approaches for the identification of
40 clinically relevant NTM isolates whose species were not reliably identified
using our routine diagnostic workflow comprising phenotypic tests and hsp65
polymerase chain reaction restriction analysis. DESIGN: We used 1) sequencing
analysis of four conserved gene targets: 16S rRNA, rpoB, hsp65 and sodA; 2) two
commercial reverse hybridisation assays; and 3) protein analysis using matrix
assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF
MS). RESULTS: Combined, but not individual, sequence analysis allowed reliable
species identification for 30/40 (75%) isolates, including species previously
unknown to be circulating in Argentina. Commercial kits outperformed our routine
identification in only 5/35 isolates, and misclassified many more. MALDI-TOF MS
accurately identified species in 22/36 (61%) isolates and did not misidentify
any. CONCLUSIONS: Commercial kits did not resolve the problem of species of NTM
isolates that elude identification. Combined DNA sequence analysis was the
approach of choice. MALDI-TOF MS shows promise as a powerful, rapid and
accessible tool for the rapid identification of clinically relevant NTM in the
diagnostic laboratory, and its accuracy can be maximised by building up a
customised NTM spectrum database.
PMID- 27510256
TI - Chronic respiratory disease and high altitude are associated with depressive
symptoms in four diverse settings.
AB - SETTING: Depression is a prevalent comorbidity of chronic respiratory disease
(CRD), and may indicate worse clinical outcomes. The relationship between
depression and living with chronic hypoxia due to CRD or residence at altitude
has received little attention in resource-poor settings. OBJECTIVE: To
investigate the association between CRD conditions and depressive symptoms in
four settings in Peru. DESIGN: We collected data on CRD and depressive symptoms
in adults aged ?35 years. Depressive symptoms were measured according to the
Center for Epidemiologic Studies Depression scale. Multivariable ordinal logistic
regression was used to assess the adjusted odds of being in a higher category of
depressive symptoms as a function of CRD. RESULTS: We analyzed data from 2953
participants (mean age 55.3 years, 49% male). The prevalence of major depressive
symptoms was 19%, with significant variation according to setting. Participants
with at least one CRD (OR 1.34, 95%CI 1.06-1.69) and those living at altitude (OR
1.64, 95%CI 1.10-2.43) had an increased adjusted odds of being in a higher
category of depressive symptoms. CONCLUSION: We found a high prevalence of
depressive symptoms, and a positive association between depressive symptoms with
CRD and with living at altitude, both of which cause chronic hypoxia.
PMID- 27510257
TI - Introduction of spirometry into clinical practice in Georgetown, Guyana: quality
and diagnostic outcomes.
AB - SETTING: Georgetown Public Hospital Corporation (GPHC), a 600-bed publicly funded
referral hospital in Georgetown, Guyana. OBJECTIVE: To assess spirometry quality
and diagnostic outcomes 2 years after the introduction of spirometry into routine
clinical practice at GPHC. DESIGN: We performed a retrospective review of 476
consecutive spirometry assessments performed from November 2013 to November 2015.
We assessed the proportion and trend of spirometry tests meeting acceptability
criteria, along with diagnostic interpretations and spirometry laboratory
referral patterns. RESULTS: Overall, 80.4% of the 454 initial spirometry
measurements on unique patients met the acceptability criteria, with no
significant change in the proportion of acceptable spirometry over the study
period (P = 0.450). Of the 369 (81.3%) first tests considered interpretable, 139
(30.6%) were normal, 151 (33.3%) were obstructive, 54 (11.9%) were suggestive of
a restrictive pattern, 25 (5.5%) were suggestive of a mixed disorder and 119
(26.2%) tests met the definition of reversibility. CONCLUSION: Over a 2-year
period, high-quality spirometry was performed in GPHC, a publicly funded hospital
in a middle-income country with no pre-existing specialised respiratory service.
PMID- 27510258
TI - Isoniazid minimal inhibitory concentrations of tuberculosis strains with katG
mutation.
PMID- 27510259
TI - Reversion of phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis.
PMID- 27510260
TI - Endobronchial valves to treat a recurrent giant emphysematous bulla after
bullectomy.
PMID- 27510261
TI - Heart failure in elderly patients: differences in clinical characteristics and
predictors of 1-year outcome in the Polish ESC-HF Long-Term Registry.
AB - INTRODUCTION Heart failure (HF) is the leading cause of hospitalization in
elderly patients. OBJECTIVES The aim of the study was to examine the clinical
profile and 1-year outcomes of elderly patients (aged >=65 years) compared with
younger patients (aged <65 years) hospitalized for HF decompensation, as well as
clinical differences among elderly patients aged 65-74 years and those aged >=75
years. PATIENTS AND METHODS The primary endpoint (PE; all-cause death) and the
secondary endpoint (SE; all-cause death or rehospitalization for HF worsening)
were assessed at 1 year in a group of 765 hospitalized Polish participants of the
ESC-HF Long-Term Registry. RESULTS The PE was observed in 9.1% of patients
aged <65 years; 18.5% of those aged >=65 years (P = 0.0001); 14.5% of those aged
65-74 years; and 21.6% of those aged >=75 years (P = 0.07). The SE occurred in
28.0% of patients aged <65 years; 36.1% of those aged >=65 years (P = 0.04);
29.2% of those aged 65-74 years; and 41.2% of those aged >=75 years (P = 0.01).
Independent predictors of the PE in patients aged >=65 years were as follows:
chronic obstructive pulmonary disease (COPD), systolic blood pressure (SBP), New
York Heart Association (NYHA) class, beta-blocker use; in patients aged 65-74
years: coronary revascularization, NYHA class, sodium, and creatinine; in
patients aged >=75 years: NYHA class and SBP. Independent predictors of the SE in
patients aged >=65 years were as follows: COPD, NYHA class, potassium, SBP, and
physical activity; in patients aged <65 years: chronic kidney disease (CKD),
NYHA, and SBP; in patients aged 65-74 years: NYHA and creatinine; and in patients
aged >=75 years, previous HF hospitalization, coronary artery disease, CKD, COPD,
alcohol consumption, smoking, NYHA, and SBP. CONCLUSIONS Elderly patients with
HF differed from younger patients in terms of long-term outcome and prognostic
factors. There were also important differences within the elderly group itself.
PMID- 27510262
TI - Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis.
AB - Osteoarthritis (OA) is a chronic degenerative disease affecting articular
cartilage in joints, and it is a leading cause of disability in the United
States. Current pharmacological treatment strategies are ineffective to prevent
the OA progression; however, cellular therapies have the potential to regenerate
the lost cartilage, combat cartilage degeneration, provide pain relief, and
improve patient mobility. One of the most promising sources of cellular
regenerative medicine is from mesenchymal stem cells (MSCs). MSCs can be isolated
from adipose tissue, bone marrow, synovial tissue, and other sources. The aim of
this review is to compile recent advancement in cellular based therapy more
specifically in relation to MSCs in the treatment of osteoarthritis.
PMID- 27510263
TI - Does it make sense to target one tumor cell chemotactic factor or its receptor
when several chemotactic axes are involved in metastasis of the same cancer?
AB - The major problem with cancer progression and anti-cancer therapy is the inherent
ability of cancer cells to migrate and establish distant metastases. This ability
to metastasize correlates with the presence in a growing tumor of cells with a
more malignant phenotype, which express certain cancer stem cell markers. The
propensity of malignant cells to migrate and their resistance to radio
chemotherapy somewhat mimics the properties of normal developmentally early stem
cells that migrate during organogenesis in the developing embryo. In the past,
several factors, including cell migration-promoting cytokines, chemokines, growth
factors, bioactive lipids, extracellular nucleotides, and even H(+) ions, were
found to influence the metastasis of cancer cells. This plethora of pro-migratory
factors demonstrates the existence of significant redundancy in the
chemoattractants for cancer cells. In spite of this obvious fact, significant
research effort has been dedicated to demonstrating the crucial involvement of
particular pro-metastatic factor-receptor axes and the development of new drugs
targeting one receptor or one chemoattractant. Based on our own experience
working with a model of metastatic rhabdomyosarcoma as well as the work of
others, in this review we conclude that targeting a single receptor-ligand pro
metastatic axis will not effectively prevent metastasis and that we should seek
other more effective therapeutic options.
PMID- 27510265
TI - Accurate Estimation of the Intrinsic Dimension Using Graph Distances: Unraveling
the Geometric Complexity of Datasets.
AB - The collective behavior of a large number of degrees of freedom can be often
described by a handful of variables. This observation justifies the use of
dimensionality reduction approaches to model complex systems and motivates the
search for a small set of relevant "collective" variables. Here, we analyze this
issue by focusing on the optimal number of variable needed to capture the salient
features of a generic dataset and develop a novel estimator for the intrinsic
dimension (ID). By approximating geodesics with minimum distance paths on a
graph, we analyze the distribution of pairwise distances around the maximum and
exploit its dependency on the dimensionality to obtain an ID estimate. We show
that the estimator does not depend on the shape of the intrinsic manifold and is
highly accurate, even for exceedingly small sample sizes. We apply the method to
several relevant datasets from image recognition databases and protein multiple
sequence alignments and discuss possible interpretations for the estimated
dimension in light of the correlations among input variables and of the
information content of the dataset.
PMID- 27510268
TI - Electrospun superhydrophobic polystyrene hollow fiber as a probe for liquid
liquid microextraction with gas chromatography-mass spectrometry.
AB - A superhydrophobic polystyrene hollow fiber was electrospun around a copper
spring collector. This approach led to the construction of a hollow fiber
membrane, and the copper spring acted as a scaffold. The characteristic
properties of the hollow fiber were studied by scanning electron microscopy. The
membrane was used as a probe to transfer the extracting solvent from aquatic
media to a gas chromatograph. After performing the liquid-liquid microextraction
procedure on 10 mL of water sample by octanol, the whole solution was passed
through the prepared polystyrene hollow fiber. Propanol, containing 2 mg/L
lindane as the internal standard, was used for desorption and an aliquot of 2 MUL
of the desorbing solvent was subsequently injected into gas chromatography with
mass spectrometry. Effects of different parameters influencing the extraction
efficiency were optimized. The limits of detection and quantification were 2 and
6 ng/L, respectively. The relative standard deviations at a concentration level
of 100 ng/L were between 2 and 6% (n = 3) while the method linearity ranged from
6 to 200 ng/L. Some real water samples were analyzed by the developed method and
relative recoveries were in the range of 76-107%.
PMID- 27510264
TI - Clinical significance of T cell metabolic reprogramming in cancer.
AB - Conversion of normal cells to cancer is accompanied with changes in their
metabolism. During this conversion, cell metabolism undergoes a shift from
oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect,
which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis
functions in parallel with the TCA cycle and other metabolic pathways to enhance
biosynthetic processes and thus support proliferation and growth. Similar
metabolic features are observed in T cells during activation but, in contrast to
cancer, metabolic transitions in T cells are part of a physiological process.
Currently, there is intense interest in understanding the cause and effect
relationship between metabolic reprogramming and T cell differentiation. After
the recent success of cancer immunotherapy, the crosstalk between immune system
and cancer has come to the forefront of clinical and basic research. One of the
key goals is to delineate how metabolic alterations of cancer influence
metabolism-regulated function and differentiation of tumor resident T cells and
how such effects might be altered by immunotherapy. Here, we review the unique
metabolic features of cancer, the implications of cancer metabolism on T cell
metabolic reprogramming during antigen encounters, and the translational
prospective of harnessing metabolism in cancer and T cells for cancer therapy.
PMID- 27510267
TI - Neuroserpin Attenuates H2O2-Induced Oxidative Stress in Hippocampal Neurons via
AKT and BCL-2 Signaling Pathways.
AB - Oxidative stress plays a critical role in neuronal injury and is associated with
various neurological diseases. Here, we explored the potential protective effect
of neuroserpin against oxidative stress in primary cultured hippocampal neurons.
Our results show that neuroserpin inhibits H2O2-induced neurotoxicity in
hippocampal cultures as measured by WST, LDH release, and TUNEL assays. We found
that neuroserpin enhanced the activation of AKT in cultures subjected to
oxidative stress and that the AKT inhibitor Ly294002 blocked this neuroprotective
effect. Neuroserpin increased the expression of the anti-apoptotic protein BCL-2
and blocked the activation of caspase-3. Neuroserpin did not increase the level
of neuroprotection over levels seen in neurons transduced with a BCL-2 expression
vector, and an inhibitor of Trk receptors, K252a, did not block neuroserpin's
effect. Taken together, our study demonstrates that neuroserpin protects against
oxidative stress-induced dysfunction and death of primary cultured hippocampal
neurons through the AKT-BCL-2 signaling pathway through a mechanism that does not
involve the Trk receptors and leads to inhibition of caspase-3 activation.
PMID- 27510269
TI - Metal-free reductive coupling of C[double bond, length as m-dash]O and C[double
bond, length as m-dash]N bonds driven by visible light: use of perylene as a
simple photoredox catalyst.
AB - Perylene, a simple polycyclic aromatic hydrocarbon, was used as a photoredox
catalyst to enable the reductive coupling reaction of aromatic aldehydes,
ketones, and an imine under visible-light irradiation using a white LED.
PMID- 27510266
TI - Efficient liver repopulation of transplanted hepatocyte prevents cirrhosis in a
rat model of hereditary tyrosinemia type I.
AB - Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme
fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are
phenotypically analogous to human HT1, but do not recapitulate all the chronic
features of the human disorder, especially liver fibrosis and cirrhosis. Rats as
an important model organism for biomedical research have many advantages over
other animal models. Genome engineering in rats is limited till the availability
of new gene editing technologies. Using the recently developed CRISPR/Cas9
technique, we generated Fah(-/-) rats. The Fah(-/-) rats faithfully represented
major phenotypic and biochemical manifestations of human HT1, including
hypertyrosinemia, liver failure, and renal tubular damage. More importantly, the
Fah(-/-) rats developed remarkable liver fibrosis and cirrhosis, which have not
been observed in Fah mutant mice or pigs. Transplantation of wild-type
hepatocytes rescued the Fah(-/-) rats from impending death. Moreover, the highly
efficient repopulation of hepatocytes in Fah(-/-) livers prevented the
progression of liver fibrosis to cirrhosis and in turn restored liver
architecture. These results indicate that Fah(-/-) rats may be used as an animal
model of HT1 with liver cirrhosis. Furthermore, Fah(-/-) rats may be used as a
tool in studying hepatocyte transplantation and a bioreactor for the expansion of
hepatocytes.
PMID- 27510271
TI - Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects
in Olfactory Bulbectomized Mice.
AB - Magnolol is the main constituent of Magnolia bark and has been reported to
exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and
neurotrophins such as brain-derived neurotrophic factor are integrally involved
in the action of conventional antidepressants. Here, we investigated the effects
of magnolol on depressive behaviours, impaired hippocampal neurogenesis and
neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse
model of depression. Mice were submitted to OBX to induce depressive behaviour,
which was evaluated in the tail suspension test. Magnolol was administered orally
by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN,
a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation
levels of protein kinase B (Akt), extracellular signal-regulated kinase and
cyclic AMP-responsive element-binding protein were evaluated by Western blot.
Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved
OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol
significantly rescued impairments of hippocampal neurogenesis. Moreover, single
treatments with magnolol (50 mg/kg) significantly increased phosphorylation of
Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element
binding protein after 3 h. The present data indicate that magnolol exerts
antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis
and neurotrophin-related intracellular signalling in OBX mice. Copyright (c) 2016
John Wiley & Sons, Ltd.
PMID- 27510270
TI - The in silico identification and characterization of a bread wheat/Triticum
militinae introgression line.
AB - The capacity of the bread wheat (Triticum aestivum) genome to tolerate
introgression from related genomes can be exploited for wheat improvement. A
resistance to powdery mildew expressed by a derivative of the cross-bread wheat
cv. Tahti * T. militinae (Tm) is known to be due to the incorporation of a Tm
segment into the long arm of chromosome 4A. Here, a newly developed in silico
method termed rearrangement identification and characterization (RICh) has been
applied to characterize the introgression. A virtual gene order, assembled using
the GenomeZipper approach, was obtained for the native copy of chromosome 4A; it
incorporated 570 4A DArTseq markers to produce a zipper comprising 2132 loci. A
comparison between the native and introgressed forms of the 4AL chromosome arm
showed that the introgressed region is located at the distal part of the arm. The
Tm segment, derived from chromosome 7G, harbours 131 homoeologs of the 357 genes
present on the corresponding region of Chinese Spring 4AL. The estimated number
of Tm genes transferred along with the disease resistance gene was 169.
Characterizing the introgression's position, gene content and internal gene order
should not only facilitate gene isolation, but may also be informative with
respect to chromatin structure and behaviour studies.
PMID- 27510272
TI - In silico insights into the solvation characteristics of the ionic liquid 1
methyltriethoxy-3-ethylimidazolium acetate for cellulosic biomass.
AB - Lignocellulosic biomass is a domestically grown, sustainable, and potentially
carbon-neutral feedstock for the production of liquid fuels and other value added
chemicals. This underutilized renewable feedstock has the potential to alleviate
some of the current socio-economic dependence on foreign petroleum supplies while
stimulating rural economies. Unfortunately, the potential of biomass has largely
been underdeveloped due to the recalcitrant nature of lignocellulosic materials.
Task-specific ionic liquids (ILs) have shown considerable promise as an
alternative non-aqueous solvent for solvation and deconstruction of
lignocellulose in the presence of metal chloride catalyst or enzymes. Recently it
has been hypothesized that adding oxygen atoms to the tail of an imidazolium
cation would alleviate some of the negative characteristics of the ILs by
increasing mass transport properties, and decreasing IL deactivation of enzymes,
while at the same time retaining favorable solvation characteristics for
lignocellulose. Reported here are fully atomistic molecular dynamic simulations
of 1-methyltriethoxy-3-ethylimidazolium acetate ([Me-(OEt)3-Et-IM(+)] [OAc(-)])
that elucidate promising molecular-level details pertaining to the solvation
characteristics of model compounds of cellulose, and IL-induced side-chain and
ring puckering conformations. It is found that the anion interactions with the
saccharide induce alternate ring puckering conformations from those seen in
aqueous environments (i.e.(1)C4), while the cation interactions are found to
influence the conformation of the omega dihedral. These perturbations in
saccharide structures are discussed in the context of their contribution to the
disruption of hydrogen bonding in cellulosic architecture and their role in
solvation.
PMID- 27510278
TI - A targeted proteomics approach to the quantitative analysis of ERK/Bcl-2-mediated
anti-apoptosis and multi-drug resistance in breast cancer.
AB - Apoptosis suppression caused by overexpression of anti-apoptotic proteins is a
central factor to the acquisition of multi-drug resistance (MDR) in breast
cancer. As a highly conserved anti-apoptotic protein, Bcl-2 can initiate an anti
apoptosis response via an ERK1/2-mediated pathway. However, the details therein
are still far from completely understood and a quantitative description of the
associated proteins in the biological context may provide more insights into this
process. Following our previous attempts in the quantitative analysis of MDR
mechanisms, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based
targeted proteomics was continually employed here to describe ERK/Bcl-2-mediated
anti-apoptosis. A targeted proteomics assay was developed and validated first for
the simultaneous quantification of ERK1/2 and Bcl-2. In particular, ERK isoforms
(i.e., ERK1 and ERK2) and their differential phosphorylated forms including
isobaric ones were distinguished. Using this assay, differential protein levels
and site-specific phosphorylation stoichiometry were observed in parental drug
sensitive MCF-7/WT cancer cells and drug-resistant MCF-7/ADR cancer cells and
breast tissue samples from two groups of patients who were either suspected or
diagnosed to have drug resistance. In addition, quantitative analysis of the time
course of both ERK1/2 and Bcl-2 in doxorubicin (DOX)-treated MCF-7/WT cells
confirmed these findings. Overall, we propose that targeted proteomics can be
used generally to resolve more complex cellular events.
PMID- 27510273
TI - Optimizing identification and management of COPD patients - reviewing the role of
the community pharmacist.
AB - The aim of this paper was to propose key steps for community pharmacist
integration into a patient care pathway for chronic obstructive pulmonary disease
(COPD) management. A literature search was conducted to identify publications
focusing on the role of the community pharmacist in identification and management
of COPD. The literature search highlighted evidence supporting an important role
for pharmacists at each of the four key steps in the patient care pathway for
COPD management. Step 1 (primary prevention): pharmacists are ideally placed to
provide information on disease awareness and risk prevention campaigns, and to
encourage lifestyle interventions, including smoking cessation. Step 2 (early
detection/case finding): pharmacists are often the first point of contact between
the patient and the healthcare system and can therefore play an important role in
the early identification of patients with COPD. Step 3 (management and ongoing
support): pharmacists can assist patients by providing advice and education on
dosage, inhaler technique, treatment expectations and the importance of
adherence, and by supporting self-management, including recognition and treatment
of COPD exacerbations. Step 4 (review and follow-up): pharmacists can play an
important role in monitoring adherence and ongoing inhaler technique in patients
with COPD. In summary, pharmacists are ideally positioned to play a vital role in
all key stages of an integrated COPD patient care pathway from early disease
detection to the support of management plans, including advice and counselling
regarding medications, inhaler technique and treatment adherence. Areas requiring
additional consideration include pharmacist training, increasing awareness of the
pharmacist role, administration and reimbursement, and increasing physician
pharmacist collaboration.
PMID- 27510279
TI - Time-of-flight secondary ion mass spectrometry to assess spatial distribution of
A2E and its oxidized forms within lipofuscin granules isolated from human retinal
pigment epithelium.
AB - Lipofuscin granules accumulate in the cells of retinal pigment epithelium with
age, particularly in patients with hereditary diseases. These granules are
heterogeneous, being composed of mixtures of proteins and lipids, including more
than 21 different fluorescent compounds. Bisretinoids and their photo-oxidation
and photodegradation products represent the main source of lipofuscin
fluorescence and exhibit phototoxic properties. This study used time-of-flight
secondary ion mass spectrometry (ToF-SIMS) with in-depth probing to assess the
depth distribution of N-retinylidene-N-retinylethanolamine (A2E) and its singly
and doubly oxidized forms (A2E-ox and A2E-2ox, respectively) within lipofuscin
granules and in their surface layer (lipid membrane). ToF-SIMS showed that A2E
and its oxidized forms were uniformly distributed throughout lipofuscin granules
but were not present at the membrane surface layer. This finding is important for
understanding the process involved in the formation of lipofuscin granules and in
their toxicity.
PMID- 27510280
TI - Chemiluminescence of nitrogen-rich quantum dots in diperiodatoargentate(III)
solution and its application in ferulic acid analysis.
AB - A novel chemiluminescence (CL) system based on the reaction of fluorescent water
soluble nitrogen-rich quantum dots (N-dots) and diperiodatoargentate(III) (DPA)
was developed. The prepared N-dots have a small size (<=10 nm) and high
percentage of nitrogen (39.9 %), which exceeds the content of carbon in the same
N-dots. The N-dots exhibit characteristic blue fluorescence under UV light and up
conversion luminescence. The relatively intense CL emission is based on the
direct oxidation of N-dots by DPA. The CL emission may be attributed to the high
nitrogen content and the special structure of the N-dots. The CL mechanism of N
dots and DPA was investigated by using CL, UV-Vis absorption, IR, fluorescence,
and radical scavenging experiments. This investigation provides a way to study
the optical properties of N-dots. The analytical applicability of the N-dots and
DPA CL system in the determination of ferulic acid (FA) was explored. The CL
intensity was linearly proportional to the concentration of ferulic acid from 3.0
* 10-7 to 1.0 * 10-5 g mL-1 with a detection limit of 8.0 * 10-8 g mL-1 (3sigma);
the relative standard deviation was 2.4 % for 4.0 * 10-7 g mL-1 FA (n = 9). The
proposed method was successfully applied to the determination of ferulic acid in
Angelica sinensis. The study provides valuable insight into the role of nitrogen
rich quantum dots in CL.
PMID- 27510281
TI - SALDI-TOF-MS analyses of small molecules (citric acid, dexasone, vitamins E and
A) using TiO2 nanocrystals as substrates.
AB - Surface-assisted laser desorption/ionisation time-of-flight mass spectrometry
(SALDI-TOF-MS) might be the method of choice for the analysis of low mass
molecules (less than m/z 500). Titanium dioxide (TiO2) nanocrystals as a
substrate for SALDI-TOF-MS improve the reproducibility of the signal intensities
and prevent the fragmentation of some molecules upon laser irradiation, as we
have previously shown. In addition, variously shaped and sized TiO2
nanocrystals/substrates for SALDI-MS could be used for quantification of small
molecules, which are otherwise difficult to detect with the assistance of organic
matrices. TiO2-assisted LDI-MS spectra could be acquired with excellent
reproducibility and repeatability and with low detection limit. In the current
study, we analysed the spectra of dexasone, citric acid, vitamin E and vitamin A
acquired with TiO2 nanocrystals of various shapes and dimensions, i.e. the
colloidal TiO2 nanoparticles (TiO2 NPs), TiO2 prolate nanospheroids (TiO2 PNSs)
and TiO2 nanotubes (TiO2 NTs). Various shapes and dimensions of substrates were
used since these factors determine desorption and ionisation processes. The
homogeneity on the target plate was compared based on signal-to-noise values of
peaks of interest of analysed molecules as well as the within-day and day-to-day
repeatability. In summary, the obtained results show that the applicability of
individual TiO2 nanocrystals depends on the analyte. Signals which are acquired
with the assistance of TiO2 PNSs have the highest sensitivity and reproducibility
(the smallest standard deviation), even compared with those in the LDI mode. This
implies that TiO2 PNSs could also be suitable for quantitative analyses of small
molecules.
PMID- 27510282
TI - Further development on DMFC device used for analytical purpose: real applications
in the pharmaceutical field and possible in biological fluids.
AB - The analytical research devoted to the utilization of the direct methanol fuel
cell (DMFC) for analytical purposes has been continued. The research reported in
this paper concerns two points, one of which was the possibility of improving the
features, from the analytical point of view, of a catalytic fuel cell for
methanol and ethanol, by introducing an enzyme, immobilized into a dialysis
membrane small bag, in the anodic area of the fuel cell. This objective has been
fully achieved, particularly using the enzyme alcohol dehydrogenase, which has
increased the sensitivity of the method and reduced dramatically the response
time of the cell. The second point concerned the opportunity to determine two
particular antibiotics having an alcohol functional group in their molecule, that
is, imipenem and chloramphenicol. Also, this goal has been reached, even if the
sensitivity of the method is not so high. Graphical abstract Imipenem and
Chloramphenicol determination using the DMFC and Ethanol determination using the
enzymatic DMFC.
PMID- 27510284
TI - The Emergence of Flood Insurance in Canada: Navigating Institutional Uncertainty.
AB - Flood insurance has remained unavailable in Canada based on an assessment that it
lacks economic viability. In response to Canada's costliest flood event to date
in 2013, the Canadian insurance industry has started to develop a framework to
expand existing property insurance to cover flood damage. Research on flood
insurance has overlooked why and how insurance systems transition to expand
insurance coverage without evidence of economic viability. This article will
address this gap through a case study on the emergence of flood insurance in
Canada, and the approach to its expansion. Between 2013 and 2016, insurance
industry officials representing over 60% of premiums collected in Canada were
interviewed. These interviews revealed that flood insurance is being expanded in
response to institutional pressure, specifically external stakeholder
expectations that the insurance industry will adopt a stronger role in managing
flood risk through coverage of flood damage. Further evidence of this finding is
explored by assessing the emergence of a unique flood insurance model that
involves a risk-adjusted and optional product along with an expansion of
government policy supporting flood risk mitigation. This approach attempts to
balance industry concerns about economic viability with institutional pressure to
reduce flood risk through insurance. This analysis builds on existing research by
providing the first scholarly analysis of flood insurance in Canada, important
"empirical" teeth to existing conceptual analysis on the availability of flood
insurance, and the influence of institutional factors on risk analysis within the
insurance sector.
PMID- 27510283
TI - Spatiotemporal expression of endogenous TLR4 ligands leads to inflammation and
bone erosion in mouse collagen-induced arthritis.
AB - Increased expression of endogenous Toll-like receptor 4 (TLR4) ligands (e.g.,
Tenascin-C, S100A8/A9, citrullinated fibrinogen (cFb) immune complexes) has been
observed in patients with rheumatoid arthritis (RA). However, their roles in RA
pathogenesis are not well understood. Here, we investigated the expression
kinetics and role of endogenous TLR4 ligands in the murine model of collagen
induced arthritis (CIA). Tenascin-C was upregulated in blood early in CIA, and
correlated positively with the clinical score at day 56. Levels of S100A8/A9
increased starting from day 28, peaking at day 42, and correlated positively with
joint inflammation. Levels of anti-cFb antibodies increased during the late phase
of CIA and correlated positively with both joint inflammation and cartilage
damage. Blockade of TLR4 activation at the time of the first TLR4 ligand
upregulation prevented clinical and histological signs of arthritis. A TLR4
dependent role was also observed for Tenascin-C and cFb immune complexes in
osteoclast differentiation in vitro. Taken together, our data suggests that the
pathogenic contribution of TLR4 in promoting joint inflammation and bone erosion
during CIA occurs via various TLR4 ligands arising at different stages of
disease. The data also suggests that Blockade of TLR4 with monoclonal antibodies
is a promising strategy in RA treatment.
PMID- 27510285
TI - Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment
of localized scleroderma: a clinical and immunohistochemical randomized
controlled study.
AB - Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal
homogenized collagen synthesis. Fractional ablative laser resurfacing has been
used effectively in scar treatment via abnormal collagen degradation and
induction of healthy collagen synthesis. Therefore, fractional ablative laser can
provide an effective modality in treatment of morphea. The study aimed at
evaluating the efficacy of fractional carbon dioxide laser as a new modality for
the treatment of localized scleroderma and to compare its results with the well
established method of UVA-1 phototherapy. Seventeen patients with plaque and
linear morphea were included in this parallel intra-individual comparative
randomized controlled clinical trial. Each with two comparable morphea lesions
that were randomly assigned to either 30 sessions of low-dose (30 J/cm2) UVA-1
phototherapy (340-400 nm) or 3 sessions of fractional CO2 laser (10,600 nm-power
25 W). The response to therapy was then evaluated clinically and
histopathologically via validated scoring systems. Immunohistochemical analysis
of TGF-beta1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon
signed rank test for paired (matched) samples and Spearman rank correlation
equation were used as indicated. Comparing the two groups, there was an obvious
improvement with fractional CO2 laser that was superior to that of low-dose UVA-1
phototherapy. Statistically, there was a significant difference in the clinical
scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient
satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser
is a promising treatment modality for cases of localized morphea, with proved
efficacy of this treatment on clinical and histopathological levels.
PMID- 27510287
TI - Connecting Effective Immune Response, Fluorescent Granzyme B-like Peptide,
Specific Peptide Binding Patterns, Patients with Cancer and Viral Infection, in
Remission, Clinical Significance, and Liquid Biopsy.
AB - Functional cytotoxic-T-lymphocytes (CTL) with granzyme B play an important role
in an effective immune response to tumor growth and infection progression. Tumor
cells and platelets in peripheral whole blood smears of cancer patients have
shown the presence of innate binding targets for GP1R, a fluorescent synthetic
Granzyme B-like peptide. It is not known if similar GP1R-binding targets and
specific binding patterns are detectable in peripheral blood of patients with
viral infection. It is also not known if a specific binding pattern may be
associated with an effective immune response to indicate a favorable prognosis.
We reviewed the GP1R-binding patterns in the peripheral blood smears of 5
patients in remission at the time of sampling (3 with cancer and 2 with flu-like
symptoms) and a negative control. We show with fluoroscopic images that there
are: 1) fluorescent GP1R-binding targets mostly in the cytoplasmic areas of
nucleated cells in patients with breast and lung cancer who have longer survival,
2) intense fluorescent deposits mostly in the nuclear areas of segmented
neutrophils in patients recovered from severe to mild flu-like symptoms, 3)
discernible fluorescent deposits in the cytoplasmic areas of small lymphocyte
like elements and overall intense fluorescent stain in large cells in the patient
with advanced pancreatic cancer who had shorter survival, 4) GP1R-binding targets
in numerous platelet-like elements in all 5 patients. The control sample did not
show similar binding patterns. The potential association between specific GP1R
binding patterns in peripheral blood samples and prognostic significance, and its
use as liquid biopsy are discussed.
PMID- 27510288
TI - The impact of physical function on participation in the first year post-stroke.
AB - OBJECTIVES: Studies have investigated predictors of participation and showed that
fewer depressive symptoms, physical independence, and age could predict the level
of participation after stroke. Association between self-assessed functions and
perceived levels of participation over time is not yet known. The aim of this
study was to investigate perceptions of participation and how this related to
background characteristics and self-assessed rehabilitation outcomes, at 1, 6,
and 12 months post-stroke. MATERIALS AND METHODS: To capture experienced
functioning and participation, a self-assessment questionnaire, the Stroke Impact
Scale (SIS), was used at 1, 6, and 12 months post-stroke. Possible variables with
impact on perceived participation were investigated with logistic regression:
perceived physical functions, memory and thinking, emotion and communication
(SIS), as well as background characteristics. In addition, directions,
distributions, and strength of correlations between each independent variable and
the participation domain were analyzed using scatterplots. RESULTS: Participation
scores were widely distributed during the first year post-stroke. Significant
associations were only found between perceived Physical score and participation
during the first year post-stroke (1 month, n=92, P<.001; 6 months, n=79, P=.001;
12 months, n=78, P=.002). A moderate-to-high participation score was observed in
combination with a high level of perceived emotional health and cognitive skills,
at 1, 6, and 12 months. CONCLUSIONS: The findings indicate that to improve
participation during the first year post-stroke, physical functioning as well as
emotional and cognitive health can be important areas of concern when forming
rehabilitation interventions.
PMID- 27510286
TI - A Synthetic Supramolecular Receptor for the Hydrosulfide Anion.
AB - Hydrogen sulfide (H2 S) has emerged as a crucial biomolecule in physiology and
cellular signaling. Key challenges associated with developing new chemical tools
for understanding the biological roles of H2 S include developing platforms that
enable reversible binding of this important biomolecule. The first synthetic
small molecule receptor for the hydrosulfide anion, HS(-) , using only
reversible, hydrogen-bonding interactions in a series of bis(ethynylaniline)
derivatives, is reported. Binding constants of up to 90 300+/-8700 m(-1) were
obtained in MeCN. The fundamental science of reversible sulfide binding, in this
case featuring a key CH???S hydrogen bond, will expand the possibility for
discovery of sulfide protein targets and molecular recognition agents.
PMID- 27510289
TI - [Not Available].
PMID- 27510290
TI - Poor Acceptability of Female Condom by Young Cameroonians: an Unmet Programmatic
Agenda for HIV Prevention.
AB - BACKGROUND: An important component of the response to the AIDS epidemic is the
prevention of HIV infection and other sexually transmitted diseases through the
use of condoms. In order to enhance HIV prevention programs and minimize the
occurrence of unwanted pregnancies, female condoms have been introduced within
the community, with the ultimate goal of reducing vulnerability of women. The
success of such a program depends on its acceptance by the target population.
METHODS: A survey was conducted among 426 respondents from different regions of
Cameroon, to evaluate their perception of HIV/AIDS and their level of acceptance
of condom usage in general, and female condom use in particular. RESULTS:
Respondents were young adults residing in seven regions of Cameroon (86.4% west,
6.5% Littoral, 3% Centre and 4.1% Adamawa, East, Far-North and North-West). Mean
age was 22.6 years; 57% were male, 95% were single, and 77% were university
educated. Overall, 76% of participants reported using condoms, though 48%
complained of decreased sexual satisfaction. Interestingly, awareness regarding
female condoms was 74.5% and 88.5% in men and women respectively, however only 8%
and 9.9% respectively reported having ever used them. Respondents generally
learnt about sexual education through broadcasting media (~90%). CONCLUSION: In
this sexually active Cameroonian population, the rate of acceptance or use of
female condom remains very low, even among women. Strategies to increase
awareness of female condoms among young women, their benefits and correct use,
are needed.
PMID- 27510291
TI - [Planning a Health Residence for Prison Security Measures, Tuscany (Italy)].
AB - Health Residences for Prison Security Measures are facilities hosting psychotic
persons who have committed crimes and providing them with personalized
rehabilitation and treatment plans to promote their reinstatement in society. The
aim of this study was to describe the criteria for planning and designing a
prison health residence in the Tuscany region (Italy), to be managed by the
regional healthcare service, in line with current regulations, with dedicated
staff for providing specific treatment plans and programmes.
PMID- 27510292
TI - [Definition and variables of complexity of nursing care: a literature review].
AB - Complexity of nursing care represents an important indicator in the planning and
management of nursing resources and healthcare management. However, the term is
not clearly defined in the literature. The aim of this article is to outline the
main concepts associated with complexity of nursing care, trying to shed light on
the different variables that constitute it. We conducted a review of the
literature and selected 12 articles. The terms associated with the concept of
complexity of nursing care include nursing intensity, nursing work, nursing
workload, patient acuity and severity of illness. The literature review indicates
that complexity of nursing care appears to be one of the variables of care
intensity, the latter being defined as a commitment of care delivered to the
patient. It is associated with the concepts of nursing work, nursing workload,
patient acuity and severity of illness. Understanding and clarifying the concept
of complexity of care is fundamental in order to measure and evaluate the real
demand for nursing care by individual patients.
PMID- 27510293
TI - [A geographical and epidemiological analysis of cancer incidence in the city of
Vercelli, Italy, 2002-2009].
AB - The idea of conducting a geographical analysis of cancer incidence in Vercelli, a
city with about 46,000 population in the Province of Vercelli (Piedmont, northern
Italy), originated from the need to respond to concerns of the population and
local administrators regarding the presence of a solid waste incinerator just a
few kilometers from the city, and the ongoing intense agricultural activity in
the area. The study also aimed to verify the excess risk identified in a similar
study on mortality. We obtained census data and mortality data for the years 2002
to 2009, from the Italian Institute of Statistics (ISTAT) and analysed these from
both an epidemiological point of view, through standardised mortality rates, and
spatial analysis through the use of Bayesian models. Both approaches highlighted
an overall increased risk for cancers and increased risks for colorectal and lung
cancer, in persons residing south of the capital. They also identified an
increased cancer risk in the young adult population of both sexes, which deserves
further investigation.
PMID- 27510294
TI - [The public health importance of vaccinations in the elderly: an evidence-based
guide].
AB - Ageing represents an extremely current issue globally, and involves especially
European populations. It is estimated that in Europe by the year 2025, about a
third of the population will be over 60 years of age, hence the imperative for
"healthy ageing". Vaccinations in seniors, in contrast with paediatric
vaccinations, are very often neglected even by health care workers. This article
aims to provide an evidence-based guide to establish vaccinations in seniors as
one of the pillars of Public Health in the future.
PMID- 27510295
TI - The effect of high-dose steroids, and normobaric oxygen therapy, on recent onset
non-arteritic anterior ischemic optic neuropathy: a randomized clinical trial.
AB - BACKGROUND: To evaluate the effect of high-dose intravenous steroids, as well as
normobaric oxygen therapy, in the management of recent onset non-arteritic
anterior ischemic optic neuropathy (NAION). METHOD: Ninety eyes of 90 patients
diagnosed with NAION within 14 days of onset were included in this single masked
randomized clinical trial. Thirty patients were randomized into each set as group
1 (control), group 2 (steroids), and group 3 (oxygen). Controls received placebo;
group 2 received methylprednisolone 500 mg twice a day for 3 days followed by 2
weeks of oral prednisolone 1 mg/kg/day; group 3 received 100 % normobaric oxygen
with mask, at a flow rate of 5 liters per minute for 1 hour twice a day for two
weeks. Functional and structural outcomes were analyzed at 1 and 6 months
following treatment. Best corrected visual acuity (BCVA) was the main outcome
measure, and mean deviation (MD) of visual field (VF) test and peripaillary
retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures.
RESULTS: The mean BCVA at the time of presentation was 1.02 +/- 0.63, 1.05 +/-
0.7, and 0.76 +/- 0.5 LogMAR in groups 1, 2, and 3, respectively (p = 0.293);
corresponding values were 0.8 +/- 0.45, 0.84 +/- 0.45, and 0.58 +/- 0.4 at month
1 (p = 0.127, 0.19, and 0.168, respectively). BCVA improved to 0.71 +/- 0.46,
0.73 +/- 0.36, and 0.59 +/- 0.41 LogMAR at the 6-month follow-up point (p =
0.039, 0.048, and 0.195, respectively). The mean deviation (MD) at the time of
presentation was 19.26 +/- 7.02, 20.51 +/- 4.68, and 19.3 +/- 7.17 in the
control, steroid, and oxygen groups, respectively (p = 0.65). Corresponding
values at month 1 were 20.26 +/- 8.52, 19.52 +/- 7.08, and 18.3 +/- 7.45, (p =
0.656); and at month 6 were 18.42 +/- 8.17, 17.66 +/- 6.44 and 16.53 +/- 6.32,
respectively (p = 0.635). PRNFLT at presentation was 166 +/- 57, 184 +/- 57, and
193 +/- 65 micrometer in the control, steroid, and oxygen groups, respectively (p
= 0.265); which decreased to 73 +/- 11, 87 +/- 26, and 79 +/- 19 at the final
foll-w up (all p < 0.001). There were no statistically significant differences
between the three groups in terms of final visual function and structure.
CONCLUSION: The lack of demonstrable improvement in the structural and functional
outcomes of NAION with high-dose IV steroids, or normobaric oxygen, in this
randomized controlled trial calls into question the administering of systemic
steroid or normobaric oxygen in this condition.
PMID- 27510296
TI - Correlation between low tapasin expression and impaired CD8+ T-cell function in
patients with chronic hepatitis B.
AB - Recent studies have demonstrated that chronic hepatitis B virus (HBV) infection
is associated with reduced antigen-presenting capacity and insufficient cytotoxic
T lymphocyte (CTL) production. The molecular chaperone tapasin mediates binding
of the transporter associated with antigen processing (TAP), and has an important
role in endogenous antigen processing and presentation, and the induction of
specific CTL responses. The present study aimed to determine whether tapasin is
associated with chronic HBV (CHB) infection. The mRNA expression levels of
tapasin were detected in peripheral blood mononuclear cells from 27 patients with
CHB, 20 patients with acute HBV (AHB) and 26 healthy controls by reverse
transcription-quantitative polymerase chain reaction. In addition, CD8+ T immune
responses were evaluated in all groups, and the correlation between tapasin
expression and CD8+ responses was analyzed. The results demonstrated that the
mRNA expression levels of tapasin were significantly downregulated in patients
with CHB compared with in healthy controls and patients with AHB. Furthermore,
the apoptotic rate of CD8+ T cells was increased in patients with CHB compared
with in the other two groups. The percentage of interferon (IFN)-gamma+CD8+ T
cells was reduced in patients with CHB compared with in patients with AHB and
healthy controls, and serum cytokine levels (IFN-gamma, interleukin-2 and tumor
necrosis factor-alpha) were generally low in patients with CHB. Furthermore, the
mRNA expression levels of tapasin were positively correlated with IFN-gamma
production by CD8+ T cells, and were inversely correlated with the apoptotic
ratio of CD8+ T cells. These results indicate that decreased expression of
tapasin may be closely associated with CHB, and suggest an important role for
tapasin in the pathogenesis of CHB.
PMID- 27510297
TI - Membrane bile acid receptor TGR5 predicts good prognosis in ampullary
adenocarcinoma patients with hyperbilirubinemia.
AB - Bile acids are potential carcinogens in gastrointestinal cancer, and interact
with nuclear and membrane receptors to initiate downstream signaling. The effect
of TGR5 [also known as G protein-coupled bile acid receptor 1 (GPBAR1)] on cancer
progression is dependent on the tissue where it is activated. In this report, the
function of TGR5 expression in cancer was studied using a bioinformatic approach.
TGR5 expression in ampullary adenocarcinoma and normal duodenum was compared by
western blotting, reverse transcription polymerase chain reaction, and
immunohistochemistry (IHC). High GPBAR1 gene expression was found to be an
indicator of worse prognosis in gastric and breast cancer patients, and an
indication of better prognosis in ovarian cancer patients. The level of GPBAR1
gene expression was higher in bile-acid exposed cancer than in other types of
cancer, and was increased in well-differentiated ampullary adenocarcinoma.
Negative, weak or mild expression of TGR5 was correlated with younger age, higher
plasma level of total/direct bilirubin, higher plasma concentration of CA-125,
advanced tumor stage and advanced AJCC TNM stage. The disease-specific survival
rate was highest in ampullary adenocarcinoma patients with high TGR5 expression
and high total bilirubin level. In summary, TGR5 functions as a tumor-suppressor
in patients with ampullary adenocarcinoma and preoperative hyperbilirubinemia.
Further study of the suppressive mechanism may provide a new therapeutic option
for patients with ampullary adenocarcinoma.
PMID- 27510298
TI - Underrepresented Minorities in Science: ACNP Strives to Increase Minority
Representation and Inclusion.
PMID- 27510300
TI - Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and
intraplaque hemorrhage in carotid atherosclerosis.
AB - PURPOSE: The aim of this work was to quantify the extent of lipid-rich necrotic
core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. METHODS:
Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1
weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were
generated from the Dixon sequence at the acquired spatial resolution of 0.60 *
0.60 * 0.70 mm voxel size. MRI and three-dimensional (3D) histology volumes of
plaques were registered. The registration matrix was applied to segmentations
denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and
without LRNC and IPH. RESULTS: Five patients were included. Regarding volumes of
LRNC identified by 3D histology, the average fat fraction by MRI was
significantly higher inside LRNC than outside: 12.64 +/- 0.2737% versus 9.294 +/-
0.1762% (mean +/- standard error of the mean [SEM]; P < 0.001). The same was true
for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81 +/-
1.276 s-1 versus 56.94 +/- 0.9095 s-1 (mean +/- SEM; P < 0.001). There was a
strong correlation between the cumulative fat and the volume of LRNC from 3D
histology (R2 = 0.92) as well as between cumulative R2* and IPH (R2 = 0.94).
CONCLUSION: Quantitative mapping of fat and R2* from Dixon MRI reliably
quantifies the extent of LRNC and IPH. Magn Reson Med 78:285-296, 2017. (c) 2016
International Society for Magnetic Resonance in Medicine.
PMID- 27510301
TI - Vibriosis, not cholera: toxigenic Vibrio cholerae non-O1, non-O139 infections in
the United States, 1984-2014.
AB - Toxigenic strains of Vibrio cholerae serogroups O1 and O139 have caused cholera
epidemics, but other serogroups - such as O75 or O141 - can also produce cholera
toxin and cause severe watery diarrhoea similar to cholera. We describe 31 years
of surveillance for toxigenic non-O1, non-O139 infections in the United States
and map these infections to the state where the exposure probably originated.
While serogroups O75 and O141 are closely related pathogens, they differ in how
and where they infect people. Oysters were the main vehicle for O75 infection.
The vehicles for O141 infection include oysters, clams, and freshwater in lakes
and rivers. The patients infected with serogroup O75 who had food traceback
information available ate raw oysters from Florida. Patients infected with O141
ate oysters from Florida and clams from New Jersey, and those who only reported
being exposed to freshwater were exposed in Arizona, Michigan, Missouri, and
Texas. Improving the safety of oysters, specifically, should help prevent future
illnesses from these toxigenic strains and similar pathogenic Vibrio species.
Post-harvest processing of raw oysters, such as individual quick freezing, heat
cool pasteurization, and high hydrostatic pressurization, should be considered.
PMID- 27510302
TI - Characterization of two LuxI/R homologs in Pantoea ananatis LMG 2665T.
AB - Quorum sensing (QS) plays an important role in the regulation of bacteria-host
interactions and ecological fitness in many bacteria. In this study, 2 luxI/R
homologs, namely eanI/eanR and rhlI/rhlR, were identified in the genome sequence
of Pantoea ananatis LMG 2665T. To determine a role for these luxI/R homologs in
pathogenicity and biofilm formation, mutant bacterial strains lacking either
eanI/R or rhlI/R and both of these homologs were generated. The results indicated
that both the RhlI/R and EanI/R systems are required for pathogenicity and
biofilm formation in strain LMG 2665T. This is the first study to characterize
the biological significance of the RhlI/R QS system in P. ananatis.
PMID- 27510303
TI - Genetic diversity of 21 autosomal STR loci in the Han Chinese population from
Hainan Province in South China.
PMID- 27510305
TI - Analyzing generalized coherent states for a free particle.
AB - Despite the didactic importance of a free particle in quantum mechanics, its
coherent state analysis has long been untouched. It is only recently that it has
been noticed and studied in the semiclassical domain. While the previously known
solutions, reported by Bagrov et al. for a free particle, are described using the
linear non-Hermitian invariant operator, we show in this work that the general
solution of the Schrodinger equation can also be naturally derived using a
simpler method based on an Hermitian linear invariant operator. According to
this, an exact Gaussian wave function that corresponds to a coherent state
solution is obtained. An interpretation for such general quantum solution
designated within the Lewis-Riesenfeld framework is provided and, further,
quantum-classical correspondence principle for the system is reexamined.
PMID- 27510304
TI - Electrical coupling regulates layer 1 interneuron microcircuit formation in the
neocortex.
AB - The coexistence of electrical and chemical synapses among interneurons is
essential for interneuron function in the neocortex. However, it remains largely
unclear whether electrical coupling between interneurons influences chemical
synapse formation and microcircuit assembly during development. Here, we show
that electrical and GABAergic chemical connections robustly develop between
interneurons in neocortical layer 1 over a similar time course. Electrical
coupling promotes action potential generation and synchronous firing between
layer 1 interneurons. Furthermore, electrically coupled interneurons exhibit
strong GABA-A receptor-mediated synchronous synaptic activity. Disruption of
electrical coupling leads to a loss of bidirectional, but not unidirectional,
GABAergic connections. Moreover, a reduction in electrical coupling induces an
increase in excitatory synaptic inputs to layer 1 interneurons. Together, these
findings strongly suggest that electrical coupling between neocortical
interneurons plays a critical role in regulating chemical synapse development and
precise formation of circuits.
PMID- 27510306
TI - Dynamic NMR and Quantum-Chemical Study of the Stereochemistry and Stability of
the Chiral MoO2(acac)2 Complex in Solution.
AB - The stereochemistry and dynamics of MoO2(acac)2 in benzene, chloroform, and
toluene were investigated by variable temperature (1)H NMR, density functional
theory (SOGGA11-X, B3LYP), and ab initio (MP2) methods. In solution, an
equilibrium between two chiral enantiomers with C2 symmetry was identified,
Lambda-cis-MoO2(acac)2 and Delta-cis-MoO2(acac)2. The two enantiomers are
connected via achiral cis transition states that switch the enantiomeric
conformations via a Ray-Dutt, Bailar, and a newly described racemization twisting
mechanism. All three mechanisms have similar calculated activation energies.
Activation parameters Ea, DeltaH(?), and DeltaS(?) were experimentally determined
for the exchange process, with a small, negative DeltaS(?), and a positive
DeltaH(?) of 68.1 kJ mol(-1) in benzene, 54.9 kJ mol(-1) in chloroform, and 60.6
kJ mol(-1) in toluene, in reasonable general agreement with the calculations.
Trans configurations of MoO2(acac)2 are very much higher in energy than cis and
are not relevant in the temperature range experimentally studied, 243-340 K. The
enantiomers interconvert within seconds near room temperature and much faster at
elevated temperatures. Racemization will thus prevent the use of enantiomerically
pure MoO2(acac)2 for chiral catalysis under practical conditions.
PMID- 27510307
TI - Differential pre-amplification of STR loci for fragmented forensic DNA profiling.
AB - DNA profiling of short tandem repeats (STR) has been successfully used for the
identification of individuals in forensic samples, accidents and natural
disasters. However, STR profiling of DNA isolated from old crime scenes and
damaged biological samples is difficult due to DNA degradation and fragmentation.
Here, we show that pre-amplification of STR loci using biotinylated primers for
the STR loci is an efficient strategy to obtain STR profiling results from
fragmented forensic samples. Analysis of STR loci with longer amplicon sizes is
generally hampered, since these relatively long loci are vulnerable to DNA
fragmentation. This problem was overcome by using reduced or increased primer
concentrations for loci with shorter or longer amplicon sizes, respectively, in
our pre-amplification strategy. In addition, pre-amplification of STR loci into
two groups of short or long amplicon size increases the efficiency of STR
profiling from highly fragmented forensic DNA samples. Therefore, differential
pre-amplification of STR loci is an effective way to obtain DNA profiling results
from fragmented forensic samples.
PMID- 27510308
TI - Ultra-sensitive measurement of peroxy radicals by chemical amplification
broadband cavity-enhanced spectroscopy.
AB - The PERCA (PEroxy Radical Chemical Amplification) technique, which is based on
the catalytic conversion of ambient peroxy radicals (HO2 and RO2, where R stands
for any organic chain) to a larger amount of nitrogen dioxide (NO2) amplified by
chain reactions by adding high concentrations of NO and CO in the flow reactor,
has been widely used for total peroxy radical RO2* (RO2* = HO2 + SigmaRO2)
measurements. High-sensitivity and accurate measurement of the NO2 concentration
plays a key role in accurate measurement of the RO2* concentration. In this
paper, we report on the development of a dual-channel chemical amplification
instrument, which combined the PERCA method with the incoherent broadband cavity
enhanced absorption spectroscopy (IBBCEAS), for peroxy radical measurements. The
IBBCEAS method is capable of simultaneously measuring multiple species with high
spectral identification, and can directly measure NO2 concentrations with high
sensitivity and high accuracy and without interference from other absorbers. The
detection sensitivity of the developed PERCA-IBBCEAS instrument for HO2 radicals
was estimated to be about 0.9 pptv (1sigma, 60 s) at a relative humidity (RH) of
10%. Considering the error sources of NO2 detection, CL determination, and the
radical partitioning in the air sample, the total uncertainty of RO2*
measurements was about 16-20%.
PMID- 27510310
TI - Surgical treatment for thoracoabdominal intra-aortic thrombus with multiple
infarctions: a case report.
AB - BACKGROUND: Mobile intra-aortic thrombus without atherosclerosis, aneurysm, or
congenital coagulopathy is very rare, and there are few reports especially in
young or middle-aged patients. Furthermore, there are presently no established
guidelines or common strategies for the treatment of mobile intra-aortic
thrombus. In this case report, we describe the first case of intra-aortic
thrombus caused by secondary erythrocytosis and describe the recommended
treatment strategy for intra-aortic thrombus. CASE PRESENTATION: We report a case
of an independent 40-year-old Asian man with a current history of heavy cigarette
smoking who had sudden onset of abdominal and lumbar pain. Contrast-enhanced
computed tomography revealed partial renal and splenic infarction, and he was
transferred to our hospital. He also had a large mural thrombus in his
thoracoabdominal aorta. Blood analysis on admission showed a hemoglobin level of
19.4 g/dL and hematocrit of 54.3 %; his international normalized ratio of
prothrombin time, fibrin degradation products, and activated partial
thromboplastin time levels were 1.02, 2.8 MUg/ml, and 26.9 seconds respectively.
We could find no abnormalities in protein C and protein S activity levels. Lupus
anticoagulant and anti-cardiolipin antibody were both negative. He had no past
medical history of arrhythmia and we found no signs of an arrhythmic event during
admission. We promptly started anticoagulant therapy, but as the thrombus seemed
at high risk of causing further critical infarction, we performed emergency
aortic thrombectomy using partial extracorporeal circulation. To prevent
dissemination of the thrombus during extracorporeal circulation, we first clamped
his proximal and distal aorta on either side of the thrombus just before
initiating extracorporeal circulation. After the aortotomy we removed a 14-cm
length of intra-aortic thrombus without residual lesion. He was discharged from
our hospital 20 days after surgery. From the results of his blood analysis, we
considered the only cause of this thrombus was secondary erythrocytosis, which
was probably induced by his current heavy cigarette smoking. CONCLUSION: We are
the first to report such a thrombosis caused by secondary erythrocytosis and
conclude that once the diagnosis of intra-aortic thrombus with systemic embolism
is clear, emergency surgical removal of such a thrombus must be considered to
prevent further embolic complications.
PMID- 27510309
TI - Genotype-phenotype correlation of SMN locus genes in spinal muscular atrophy
children from Argentina.
AB - BACKGROUND/PURPOSE: Spinal muscular atrophy (SMA) is an autosomal recessive
neuromuscular disorder, considered one of the leading causes of infant mortality.
It is caused by mutations in the SMN1 gene. A highly homologous copy of this gene
named SMN2 and other neighbouring genes, SERF1A and NAIP, are considered
phenotypic modifiers of the disease. In recent years, notable advances have been
made in SMA research regarding evaluation, prognosis, and therapeutic options.
Thus, genotype-phenotype studies in SMA are important to stratify patients for
motor function tests and for envisaged clinical trials. The aim of this study was
to provide clinical and molecular data of a series of Argentinean children with
SMA to establish a comprehensive genotype-phenotype correlation. METHODS: 144
Argentinean children with SMA (56 children with type I, 58 with type II, and 30
with type III) were evaluated. The copy number of SMN2, SERF1A, and NAIP genes
was established using MLPA (Multiplex Ligation-dependent Probe Amplification) and
then correlated with the patients clinical subtypes. To improve clinical
characterization we considered the initial symptoms that prompted the
consultation, age of acquisition of motor abilities to independent walking and
age at loss of gait. We also evaluated clinical and molecular features of sibling
pairs in seven families. RESULTS: A strong correlation was observed between the
SMN2 copy number and SMA phenotype while SERF1A and NAIP copy number showed a
moderate correlation. We observed intra- and inter-family differences among the
SMA types. CONCLUSION: This first genotype-phenotype correlation study in
Argentinean SMA children provides data to improve patient stratification and
define more adequate follow-up parameters.
PMID- 27510311
TI - Engineering of Sub-Nanometer SiOx Thickness in Si Photocathodes for Optimized
Open Circuit Potential.
AB - Silicon is one of the most promising materials to be used for tandem-cell water
splitting devices. However, the electrochemical instability of bare Si makes it
difficult to be used for stable devices. Besides that, the photovoltage loss in
Si, caused by several factors (e.g., metal oxide protection layer and/or SiO2 /Si
or catalyst/Si interface), limits its use in these devices. In this work, we
present that an optimized open circuit potential (OCP) of Si can be obtained by
controlling the SiOx thickness in sub-nanometer range. It can be done by means of
a simple and cost-effective way using the combination of a wet chemical etching
and the low temperature atomic layer deposition (ALD) of TiO2 . We have found
that a certain thickness of the native SiOx is necessary to prevent further
oxidation of the Si photocathode during the ALD growth of TiO2 . Moreover,
covering the Si photocathode with an ALD TiO2 layer enhances its stability.
PMID- 27510312
TI - Local wound healing biomarkers for real-time assessment of periodontal
regeneration: pilot study.
AB - BACKGROUND AND OBJECTIVES: Within the same surgical procedure, a great
variability on achievement of clinical outcomes exists and may be associated to
different molecular factors related to tissue healing. The aim of the present
study was to assess the distribution of clinical success separately in
regenerative therapy (REG) and open flap debridement (OFD) to evaluate if factors
related with healing of epithelium, connective tissue and bone may be associated
to the clinical outcome within each surgical procedure. MATERIAL AND METHODS:
Sixteen patients underwent periodontal REG and nine patients underwent OFD.
Periodontal wound fluid was collected at baseline, 3-5, 7, 14 and 21 d after
surgery, and expression of wound healing proteins was assessed. Pocket depth and
clinical attachment level were taken at baseline and at 6 mo of follow-up.
Percentage pocket depth reduction and percentage clinical attachment level gain
were computed. Patients were regarded as better or worse responders depending on
their percentage pocket depth reduction or percentage clinical attachment level
gain. RESULTS: Higher percentage of better responders was observed in the REG
group (68.7%) compared to the OFD group (22.2%). At 21 d, no difference in the
profile of most of the proteins emerged, with two exceptions, both regarding REG
treatment. Bone morphogenetic protein-7 tended to increase in better responders
and to decrease in worse responders. Matrix metalloproteinase-1 increased in
worse responders and remained substantially unchanged in better responders.
CONCLUSION: Local expression of matrix metalloproteinase-1 and bone morphogenetic
protein-7 during wound healing is associated with the clinical performance of
periodontal regenerative surgery. The use of local biomarkers offers the
potential for real-time assessment of the periodontal healing process.
PMID- 27510313
TI - Long-term nitrous oxide fluxes in annual and perennial agricultural and unmanaged
ecosystems in the upper Midwest USA.
AB - Differences in soil nitrous oxide (N2 O) fluxes among ecosystems are often
difficult to evaluate and predict due to high spatial and temporal variabilities
and few direct experimental comparisons. For 20 years, we measured N2 O fluxes in
11 ecosystems in southwest Michigan USA: four annual grain crops (corn-soybean
wheat rotations) managed with conventional, no-till, reduced input, or
biologically based/organic inputs; three perennial crops (alfalfa, poplar, and
conifers); and four unmanaged ecosystems of different successional age including
mature forest. Average N2 O emissions were higher from annual grain and N-fixing
cropping systems than from nonleguminous perennial cropping systems and were low
across unmanaged ecosystems. Among annual cropping systems full-rotation fluxes
were indistinguishable from one another but rotation phase mattered. For example,
those systems with cover crops and reduced fertilizer N emitted more N2 O during
the corn and soybean phases, but during the wheat phase fluxes were ~40% lower.
Likewise, no-till did not differ from conventional tillage over the entire
rotation but reduced emissions ~20% in the wheat phase and increased emissions 30
80% in the corn and soybean phases. Greenhouse gas intensity for the annual crops
(flux per unit yield) was lowest for soybeans produced under conventional
management, while for the 11 other crop * management combinations intensities
were similar to one another. Among the fertilized systems, emissions ranged from
0.30 to 1.33 kg N2 O-N ha-1 yr-1 and were best predicted by IPCC Tier 1 and
DeltaEF emission factor approaches. Annual cumulative fluxes from perennial
systems were best explained by soil NO3- pools (r2 = 0.72) but not so for annual
crops, where management differences overrode simple correlations. Daily soil N2 O
emissions were poorly predicted by any measured variables. Overall, long-term
measurements reveal lower fluxes in nonlegume perennial vegetation and, for
conservatively fertilized annual crops, the overriding influence of rotation
phase on annual fluxes.
PMID- 27510314
TI - 2016 updated MASCC/ESMO consensus recommendations: Anticipatory nausea and
vomiting in children and adults receiving chemotherapy.
AB - PURPOSE: We aimed to update the 2011 recommendations for the prevention and
treatment of anticipatory nausea and vomiting in children and adults receiving
chemotherapy. METHODS: The original systematic literature search was updated.
Randomized studies were included in the evidence to support this guideline if
they as follows: were primary studies published in a journal in full text (i.e.,
abstracts, letters, book chapters, and dissertations were excluded); published in
English; evaluated an intervention for the prevention or treatment of
anticipatory nausea and vomiting; reported the proportion of patients
experiencing complete control of anticipatory nausea and vomiting consistently
and; included at least ten participants per study arm for comparative studies and
at least ten participants overall for noncomparative studies. RESULTS: Eighty
eight new citations were identified. Of these, nine were brought to full-text
screening; none met inclusion criteria. The guideline panel continues to
recommend that anticipatory nausea and vomiting are best prevented through
optimization of acute and delayed phase chemotherapy-induced nausea and vomiting
control. Benzodiazepines and behavioral therapies, in particular progressive
muscle relaxation training, systematic desensitization and hypnosis, continue to
be recommended for the treatment of anticipatory nausea and vomiting.
CONCLUSIONS: No new information regarding interventions aimed at treating or
preventing ANV that met criteria for inclusion in this systematic review was
identified. The 2015 MASCC recommendations affirm the content of the 2009 MASCC
recommendations for the prevention and treatment of anticipatory nausea and
vomiting.
PMID- 27510315
TI - Lymphedema self-care in patients with head and neck cancer: a qualitative study.
AB - PURPOSE: Lymphedema is a frequent side effect from head and neck cancer and/or
its treatment. As a chronic and progressive condition, it requires an
individual's long-term involvement in self-care for management of lymphedema.
This study aimed to report head and neck cancer patients' perceived lymphedema
education, self-care practices, and suggestions related to self-care of head and
neck lymphedema. METHODS: Twenty head and neck cancer patients who completed
lymphedema therapy participated in semi-structured face-to-face interviews.
Interviews were audio-recorded and transcribed. Content analysis was used to
analyze the interview data. RESULTS: All participants reported that they were
educated about self-care activities for lymphedema management by their lymphedema
therapists. Although most participants (n = 16, 80 %) expressed positive comments
about lymphedema self-care education, some participants (n = 7, 35 %) described
issues related to lymphedema self-care education. A majority of the participants
(n = 17, 85 %) reported that they were conducting some lymphedema self-care
activities; nonetheless, more than half of the participants (n = 11, 55 %)
delineated barriers for diminished lymphedema self-care activities over time.
Participants further indicated suggestions for improving and ensuring consistency
of lymphedema self-care. CONCLUSIONS: Opportunities exist to improve lymphedema
self-care in head and neck cancer patients. Healthcare professionals should focus
on delivering high quality and targeted information about self-care for
management of head and neck lymphedema. Interventional research is warranted to
address gaps in long-term self-care of head and neck lymphedema.
PMID- 27510316
TI - 2016 updated MASCC/ESMO consensus recommendations: Prevention of nausea and
vomiting following moderately emetogenic chemotherapy.
AB - PURPOSE: An update of the recommendations for the prophylaxis of acute and
delayed emesis induced by moderately emetogenic chemotherapy published after the
last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out.
METHODS: A systematic literature search using PubMed from January 1, 2009 to
January 6, 2015 with a restriction to papers in English was conducted. RESULTS:
Overall, two randomized phase II and seven randomized phase III studies plus the
results of three subgroup analysis of large phase III trials and those of a pilot
study have been included. CONCLUSIONS: In carboplatin-treated patients, a
moderate benefit from adding an NK1 receptor antagonist to dexamethasone and a 5
HT3 receptor antagonist has been shown. However, in oxaliplatin-treated patients,
contrasting results about the role of NK1 receptor antagonists have been
obtained. At present, it is not possible to suggest a specific 5-HT3 receptor
antagonist to use for the prevention of acute emesis in these patients. No
routine prophylaxis for delayed emesis is recommended but in patients receiving
moderately emetogenic chemotherapy with known potential for delayed emesis (e.g.,
oxaliplatin, doxorubicin, cyclophosphamide) the use of dexamethasone for days 2-3
can be considered.
PMID- 27510318
TI - Real-time multi-signal frequency tracking with a bank of notch filters to
estimate the respiratory rate from the ECG.
AB - Measuring the instantaneous frequency of a signal rapidly and accurately is
essential in many applications. However, the instantaneous frequency by
definition is a parameter difficult to determine. Fourier-based methods introduce
estimation delays as computations are performed in a time-window. Instantaneous
methods based on the Hilbert transform lack robustness. State-of-the-art adaptive
filters yield accurate estimates, however, with an adaptation delay. In this
study we propose an algorithm based on short length-3 FIR notch filters to
estimate the instantaneous frequency of a signal at each sample, in a real-time
manner and with very low delay. The output powers of a bank of the above
mentioned filters are used in a recursive weighting scheme to estimate the
dominant frequency of the input. This scheme has been extended to process
multiple inputs containing a common frequency by introducing an additional
weighting scheme upon the inputs. The algorithm was tested on synthetic data and
then evaluated on real biomedical data, i.e. the estimation of the respiratory
rate from the electrocardiogram. It was shown that the proposed method provided
more accurate estimates with less delay than those of state-of-the-art methods.
By virtue of its simplicity and good performance, the proposed method is a worthy
candidate to be used in biomedical applications, for example in health monitoring
developments based on portable and automatic devices.
PMID- 27510317
TI - Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves
Locomotor Recovery After Spinal Cord Injury in Rats.
AB - Spinal cord injury (SCI) is a devastating neurologic disorder with significant
impacts on quality of life, life expectancy, and economic burden. Although there
are no fully restorative treatments yet available, several animal and small-scale
clinical studies have highlighted the therapeutic potential of cellular
interventions for SCI. Mesenchymal stem cells (MSCs)-which are conventionally
isolated from the bone marrow-recently emerged as promising candidates for
treating SCI and have been shown to provide trophic support, ameliorate
inflammatory responses, and reduce cell death following the mechanical trauma.
Here we evaluated the human skin as an alternative source of adult MSCs suitable
for autologous cell transplantation strategies for SCI. We showed that human skin
derived MSCs (hSD-MSCs) express a range of neural markers under standard culture
conditions and are able to survive and respond to neurogenic stimulation in
vitro. In addition, using histological analysis and behavioral assessment, we
demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the
severity of tissue loss and facilitates locomotor recovery in a rat model of SCI.
Altogether, the study provides further characterization of skin-derived MSC
cultures and indicates that the human skin may represent an attractive source for
cell-based therapies for SCI and other neurological disorders. Further
investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit
tissue repair and/or locomotor recovery.
PMID- 27510319
TI - Integrative approach for inference of gene regulatory networks using lasso-based
random featuring and application to psychiatric disorders.
AB - BACKGROUND: Inferring gene regulatory networks is one of the most interesting
research areas in the systems biology. Many inference methods have been developed
by using a variety of computational models and approaches. However, there are two
issues to solve. First, depending on the structural or computational model of
inference method, the results tend to be inconsistent due to innately different
advantages and limitations of the methods. Therefore the combination of
dissimilar approaches is demanded as an alternative way in order to overcome the
limitations of standalone methods through complementary integration. Second,
sparse linear regression that is penalized by the regularization parameter
(lasso) and bootstrapping-based sparse linear regression methods were suggested
in state of the art methods for network inference but they are not effective for
a small sample size data and also a true regulator could be missed if the target
gene is strongly affected by an indirect regulator with high correlation or
another true regulator. RESULTS: We present two novel network inference methods
based on the integration of three different criteria, (i) z-score to measure the
variation of gene expression from knockout data, (ii) mutual information for the
dependency between two genes, and (iii) linear regression-based feature
selection. Based on these criterion, we propose a lasso-based random feature
selection algorithm (LARF) to achieve better performance overcoming the
limitations of bootstrapping as mentioned above. CONCLUSIONS: In this work, there
are three main contributions. First, our z score-based method to measure gene
expression variations from knockout data is more effective than similar criteria
of related works. Second, we confirmed that the true regulator selection can be
effectively improved by LARF. Lastly, we verified that an integrative approach
can clearly outperform a single method when two different methods are effectively
jointed. In the experiments, our methods were validated by outperforming the
state of the art methods on DREAM challenge data, and then LARF was applied to
inferences of gene regulatory network associated with psychiatric disorders.
PMID- 27510320
TI - Brief Group Intervention Targeting Perfectionism in Adults with Anorexia Nervosa:
Empirically Informed Protocol.
AB - OBJECTIVE: This study aimed to evaluate the perfectionism group intervention in
adults with anorexia nervosa (AN) in an inpatient setting. METHOD: Adults with AN
(N = 35) received six weekly sessions of the empirically informed intervention
with experiential exercises. Participants' self-reported perfectionism and
satisfaction were collected pre-group and post-group intervention. RESULTS:
Statistically, significant differences were observed for overall perfectionism,
concern over mistakes and personal standard dimensions of perfectionism.
Participants found the sessions useful and felt confident in using the skills
they had learnt. CONCLUSIONS: The revised perfectionism group with experiential
exercises seemed to be a practical and helpful intervention for patients with AN
in an inpatient programme. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating
Disorders Association.
PMID- 27510322
TI - Drug-induced photosensitivity: new insights into pathomechanisms and clinical
variation through basic and applied science.
AB - Drug-induced photosensitivity occurs when a drug is capable of absorbing
radiation from the sun (usually ultraviolet A) leading to chemical reactions that
cause cellular damage (phototoxicity) or, more rarely, form photoallergens
(photoallergy). The manifestation varies considerably in presentation and
severity from mild pain to severe blistering. Despite screening strategies and
guidelines in place to predict photoreactive drugs during development there are
still new drugs coming onto the market that cause photosensitivity. Thus, there
is a continuing need for dermatologists to be aware of the different forms of
presentation and the culprit drugs. Management usually involves photoprotection
and cessation of drug treatment. However, there are always cases where the
culprit drug is indispensable. The reason why some patients are susceptible while
others remain asymptomatic is not known. A potential mechanism for the phototoxic
reactions is the generation of reactive oxygen species (ROS), and there are a
number of reasons why some patients might be less able to cope with enhanced
levels of ROS.
PMID- 27510323
TI - Use of whole-exome sequencing to determine the genetic basis of signs of skin
youthfulness in Korean women.
PMID- 27510321
TI - Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair
and Hindlimb Transplant Model.
AB - This study investigates the efficacy of local and intravenous mesenchymal stem
cell (MSC) administration to augment neuroregeneration in both a sciatic nerve
cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were
harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections
and repairs were performed in three groups of Lewis (LEW) rats: negative controls
(n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs
(intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN
LEW) (n = 4) hindlimb transplants were performed and assessed for
neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic
nerve cut-and-repair and treated with either local or systemic injection of MSCs
had significant improvement in the speed of recovery of compound muscle action
potential amplitudes and axon counts when compared with negative controls.
Similarly, rats undergoing allogeneic hindlimb transplants treated with local
injection of MSCs exhibited significantly increased axon counts. Similarly,
systemic MSC treatment resulted in improved nerve regeneration following
allogeneic hindlimb transplants. Systemic administration had a more pronounced
effect on electromotor recovery while local injection was more effective at
increasing fiber counts, suggesting different targets of action. Local and
systemic MSC injections significantly improve the pace and degree of nerve
regeneration after nerve injury and hindlimb transplantation.
PMID- 27510324
TI - Deviation of sliding drops at a chemical step.
AB - The motion of partially wetting liquid drops in contact with a solid surface is
strongly affected by contact angle hysteresis and interfacial pinning. However,
the majority of models proposed for drops sliding over chemical surface patterns
consistently neglect the difference between advancing and receding contact
angles. In this article, we present a joint experimental and numerical study of
the interaction of gravity-driven drops with a chemical step formed at the
junction between a hydrophilic and a hydrophobic region. It demonstrates the
strong impact of a contact angle hysteresis contrast on the motion of drops at a
linear chemical step. Surprisingly, the smallest driving force required to drag
the drop across the step onto the lower hydrophobic surface is not observed at a
right angle of incidence. Our model reveals that the non-monotonous response of
this passive drop 'filter' is solely due to the higher advancing contact angle on
the lower surface, and creates an instance where drop motion is affected by
dissipation at the contact line rather than by surface energy.
PMID- 27510326
TI - Lumps and Bumps of the Neck in Children-Neuroimaging of Congenital and Acquired
Lesions.
AB - Neck masses present as palpable lumps and bumps in children with acquired lesions
more common than congenital ones. Assessment of the anatomical site of origin,
signal, and contrast enhancement characteristics may help define the etiology of
the lesions, eg, developmental, inflammatory, vascular, or neoplastic. The age of
the patient along with detailed clinical history and physical exam findings are
important element to narrow down the differential diagnosis. The correct final
diagnosis is essential to guide treatment as well as the urgency of intervention.
The objective of this review is to define the characteristic location, classic
and differentiating imaging features of the most frequent congenital and acquired
cervical lumps and bumps in the pediatric population.
PMID- 27510325
TI - Lycopene inhibits the cell proliferation and invasion of human head and neck
squamous cell carcinoma.
AB - Lycopene has been shown to be associated with anticancer effects in numerous
tumor types. However, the underlying mechanisms of lycopene in human head and
neck squamous cell carcinoma (HNSCC) remain to be determined. The present study
aimed to investigate the involvement of lycopene overload and the cytotoxic
effects of lycopene on HNSCC cells, and to determine the possible mechanisms
involved. Treatment with lycopene at a dose of >10 uM for >24 h inhibited the
growth of FaDu and Cal27 cells in a time- and dose-dependent manner. The clearest
increase in growth inhibition was due to the apoptotic population being
significantly increased. The invasion abilities decreased with 25 uM lycopene
exerting significant inhibitory effects (P<0.01). Mechanistic studies revealed
that lycopene induced the upregulation of the pro-apoptotic protein, B-cell
lymphoma-associated X protein, and therefore, resulted in the inhibition of the
protein kinase B and mitogen-activated protein kinase signaling pathway. These
data provided insights into the antitumor activity of lycopene in HNSCC cells.
PMID- 27510327
TI - Lipophilic Cationic Cyanines Are Potent Complex I Inhibitors and Specific in
Vitro Dopaminergic Toxins with Mechanistic Similarities to Both Rotenone and
MPP(.).
AB - We have recently reported that simple lipophilic cationic cyanines are specific
and potent dopaminergic toxins with a mechanism of toxicity similar to that of
the Parkinsonian toxin MPP(+). In the present study, a group of fluorescent
lipophilic cyanines have been used to further exploit the structure-activity
relationship of the specific dopaminergic toxicity of cyanines. Here, we report
that all cyanines tested were highly toxic to dopaminergic MN9D cells with IC50s
in the range of 60-100 nM and not toxic to non-neuronal HepG2 cells parallel to
that previously reported for 2,2'- and 4,4'-cyanines. All cyanines
nonspecifically accumulate in the mitochondria of both MN9D and HepG2 cells at
high concentrations, inhibit the mitochondrial complex I with the inhibition
potencies similar to the potent complex I inhibitor, rotenone. They increase the
reactive oxygen species (ROS) production specifically in dopaminergic cells
causing apoptotic cell death. These and other findings suggest that the complex I
inhibition, the expression of low levels of antioxidant enzymes, and presence of
high levels of oxidatively labile radical propagator, dopamine, could be
responsible for the specific increase in ROS production in dopaminergic cells.
Thus, the predisposition of dopaminergic cells to produce high levels of ROS in
response to mitochondrial toxins together with their inherent greater demand for
energy may contribute to their specific vulnerability toward these toxins. The
novel findings that cyanines are an unusual class of potent mitochondrial toxins
with specific dopaminergic toxicity suggest that their presence in the
environment could contribute to the etiology of PD similar to that of MPP(+) and
rotenone.
PMID- 27510328
TI - A simple but useful way to assess fMRI scan qualities.
AB - This short "how to" article describes a plot I find useful for assessing fMRI
data quality. I discuss the reasoning behind the plot and how it is constructed.
I create the plot in scans from several publicly available datasets to illustrate
different kinds of fMRI signal variance, ranging from thermal noise to motion
artifacts to respiratory-related signals. I also show how the plot can be used to
understand the variance removed during denoising. Code to make the plot is
provided with the article, and supplemental movies show plots for hundreds of
additional subjects.
PMID- 27510329
TI - Feeling the right force: How to contextualize the cell mechanical behavior in
physiologic turnover and pathologic evolution of the cardiovascular system.
AB - Although traditionally linked to the physiology of tissues in 'motion', the
ability of the cells to transduce external forces into coordinated gene
expression programs is emerging as an integral component of the fundamental
structural organization of multicellular organisms with consequences for cell
differentiation even from the beginning of embryonic development. The ability of
the cells to 'feel' the surrounding mechanical environment, even in the absence
of tissue motion, is then translated into 'positional' or 'social' sensing that
instructs, before the organ renewal, the correct patterning of the embryos. In
the present review, we will highlight how these basic concepts, emerging from the
employment of novel cell engineering tools, can be linked to pathophysiology of
the cardiovascular system, and may contribute to understanding the molecular
bases of some of the major cardiovascular diseases like heart failure, heart
valve stenosis and failure of the venous aorto-coronary bypass.
PMID- 27510330
TI - Pericytes for the treatment of orthopedic conditions.
AB - Pericytes and other perivascular stem cells are of growing interest in
orthopedics and tissue engineering. Long regarded as simple regulators of
angiogenesis and blood pressure, pericytes are now recognized to have MSC
(mesenchymal stem cell) characteristics, including multipotentiality, self
renewal, immunoregulatory functions, and diverse roles in tissue repair.
Pericytes are typified by characteristic cell surface marker expression
(including alphaSMA, CD146, PDGFRbeta, NG2, RGS5, among others). Although alone
no marker is absolutely specific for pericytes, collectively these markers appear
to selectively identify an MSC-like pericyte. The purification of pericytes is
most well described as a CD146+CD34-CD45- cell population. Pericytes and other
perivascular stem cell populations have been applied in diverse orthopedic
applications, including both ectopic and orthotopic models. Application of
purified cells has sped calvarial repair, induced spine fusion, and prevented
fibrous non-union in rodent models. Pericytes induce these effects via both
direct and indirect mechanisms. In terms of their paracrine effects, pericytes
are known to produce and secrete high levels of a number of growth and
differentiation factors both in vitro and after transplantation. The following
review will cover existing studies to date regarding pericyte application for
bone and cartilage engineering. In addition, further questions in the field will
be pondered, including the phenotypic and functional overlap between pericytes
and culture-derived MSC, and the concept of pericytes as efficient producers of
differentiation factors to speed tissue repair.
PMID- 27510331
TI - Factors Leading to Improved Results for Endoscopic Stenting for Metastatic
Antropyloric Adenocarcinoma. A Comparison with Gastrojejunostomy.
AB - BACKGROUND: Controversies exist about the optimal palliative management for
patients with metastatic antropyloric adenocarcinoma. The aim of this study was
to analyse the clinical outcome for patients with gastric outlet obstruction
syndrome and metastatic antropyloric adenocarcinoma, who underwent endoscopic
stenting or open gastrojejunostomy, in a prospective not randomised study.
MATERIAL: The clinical course and costs for 70 patients who had endoscopic
stenting and for 30 patients who had in the same period a gastrojejunostomy for
gastric outlet obstruction syndrome due to metastatic adenocarcinoma of the
antropyloric region were prospectively analysed. RESULTS: Hospital stay and time
to resume oral feeding was shorter in patients who had endoscopic stenting (p <
0.05). Overall costs for endoscopic stenting were lower than those for
gastrojejunostomy (11,000 versus 21,000 euros). Comparing patients who survived
more than 6 months, costs between endoscopic stenting and gastrojejunostomy were
similar (21,000 versus 22,000 euros). CONCLUSIONS: Endoscopic placement of
metallic stents offers an effective therapy in patients with advanced primay
adenocarcinoma of the antropyloric region and poor general conditions. In
patients with longer life expectancy, surgical gastroenterostomy has still a
major role. In contrast to previous reports, costs for endoscopic stenting are
similar to those of gastrojejunostomy in patients with longer life expectancy.
Laparoscopic gastrojejunostomy has the theoretical advantage to reduce these
costs with a less invasive procedure. Results for endoscopic stenting have
improved significantly in recent years.
PMID- 27510332
TI - Intensity-Modulated Radiation Therapy Is Not Associated with Perioperative or
Survival Benefit over 3D-Conformal Radiotherapy for Rectal Cancer.
AB - INTRODUCTION: The use of intensity-modulated radiation therapy (IMRT) in rectal
cancer has steadily increased over traditional 3D conformal radiotherapy (3D-CRT)
due to perceived benefit of delivering higher treatment doses while minimizing
exposure to surrounding tissues. However, IMRT is technically challenging and
costly, and its effects on rectal cancer outcomes remain unclear. MATERIAL AND
METHODS: Adults with clinical stage II and III rectal adenocarcinoma who
underwent neoadjuvant chemoradiotherapy with 45-54 Gy of radiation and surgery
were included from the 2006-2013 National Cancer Data Base. Patients were grouped
based the modality of radiation received: IMRT or 3D-CRT. Multivariable
regression modeling adjusting for demographic, clinical, and treatment
characteristics was used to examine the impact of IMRT vs. 3D-CRT on pathologic
downstaging, resection margin positivity, sphincter loss surgery, 30-day
unplanned readmission and mortality after surgery, and overall survival. RESULTS:
Among 7386 patients included, 3330 (45 %) received IMRT and 4056 (55 %) received
3D-CRT. While the mean radiation dose delivered was higher with IMRT (4735 vs.
4608 cGy, p < 0.001), it was associated with higher risks of positive margins
(adjusted odds ratio (OR) 1.57; p < 0.001) and sphincter loss surgery (OR 1.32; p
< 0.001). There were no differences between IMRT and 3D-CRT in the likelihood of
pathologic downstaging (OR 0.89, p = 0.051), unplanned readmission (OR 0.79; p =
0.07), or 30-day mortality (OR 0.61; p = 0.31) after surgery. Additionally, there
were no differences in overall survival at 8 years (IMRT vs. 3D-CRT: 64 vs. 64 %;
adjusted hazard ratio 1.06, p = 0.47). CONCLUSION: IMRT is associated with worse
local tumor control without any long-term survival benefit for patients with
locally advanced rectal cancer. Given the lack of significant advantage and the
higher cost of IMRT, caution should be exercised when using IMRT instead of
traditional 3D-CRT for rectal cancer.
PMID- 27510333
TI - Practical echocardiographic approach for risk stratification of patients with
acute pulmonary embolism.
AB - Acute pulmonary embolism remains a common cause of mortality. Early diagnosis and
appropriate risk stratification is necessary to individualize treatment strategy.
Computed tomography scan of the pulmonary arteries is routinely used to diagnose
acute pulmonary embolism and in some cases is useful to assess right ventricular
dilation. In patients with acute pulmonary embolism, right ventricular dilation
and dysfunction indicates a high-risk situation where immediate administration of
thrombolytic agent, catheter-directed thrombolysis, or surgical embolectomy could
be considered. A bedside 2D echocardiogram at the time of presentation could
provide additional morphological, functional, and hemodynamic parameters
including right ventricular dilation, McConnell's sign, reduced tricuspid annular
plane systolic excursion (TAPSE), interventricular septal flattening, abnormal
right ventricular hemodynamics and in rare cases thrombi in the inferior vena
cava, right atrium or ventricle en route to pulmonary arteries may also be
visualized. This additional information is useful for selection of appropriate
treatment modality. Thus, our objective is to provide a practical
echocardiographic approach for risk stratification of patients with acute
pulmonary embolism.
PMID- 27510335
TI - Cancer control's new STaR.
PMID- 27510334
TI - [Hepatic steatosis : Differential diagnostics and current aspects].
AB - The frequency of non-alcoholic fatty liver disease (NAFLD) has continously
increased over the last few decades in parallel with the increasing prevalence of
metabolic syndrome. With the increasing frequency of obesity and type 2 diabetes
an increase in non-alcoholic steatohepatitis (NASH) is also to be expected. The
NASH-associated liver cirrhosis and primary hepatocellular carcinoma (HCC) are
indications for liver transplantation (LTX), which is gaining importance in
Germany. In contrast, liver cirrhosis as a result of alcoholic steatohepatitis
(ASH) is already the leading cause for LTX in Germany. A significant number of
patients with ASH cirrhosis develop HCC. Less common causes of hepatic steatosis
are secondary and include chemotherapy-associated steatohepatitis (CASH). In this
article the causes, diagnostics and novel therapeutic approaches for the various
forms of steatosis are discussed.
PMID- 27510337
TI - Behavioural innovation is key to improving the health of one million Australians
living with type 2 diabetes.
PMID- 27510338
TI - The Paleo diet and diabetes.
PMID- 27510339
TI - Obesity before pregnancy: new evidence and future strategies.
PMID- 27510340
TI - Pitting and non-pitting oedema.
PMID- 27510341
TI - Homage to my skull.
PMID- 27510342
TI - The problem with modern endocrinology.
PMID- 27510343
TI - Preventing all the complications of hyperglycaemia: not a straightforward task.
PMID- 27510345
TI - Correction.
PMID- 27510344
TI - Contemporary type 1 diabetes pregnancy outcomes: impact of obesity and glycaemic
control.
AB - OBJECTIVE: To compare contemporary pregnancy outcomes in women with and without
type 1 diabetes, and to examine the effects of obesity and glycaemic control on
these outcomes. DESIGN AND SETTING: Historical cohort study in a specialist
diabetes and maternity network in Victoria. PARTICIPANTS: All singleton births
(at least 20 weeks' gestation), 2010-2013, were analysed: 107 pregnancies to
women with type 1 diabetes and 27 075 pregnancies to women without diabetes.
Women with type 2 diabetes or gestational diabetes were excluded. METHODS: Data
were extracted from the Birthing Outcomes System database; associations between
type 1 diabetes and pregnancy outcomes were analysed by multivariable regression.
MAIN OUTCOME MEASURES: Mode of birth; maternal and neonatal outcomes. RESULTS:
The mean body mass index was higher for women with type 1 diabetes than for women
without diabetes (mean, 27.3 kg/m(2) [SD, 5.0] v 25.7 kg/m(2) [SD, 5.9]; P =
0.01); the median gestation period for their babies was shorter (median, 37.3
weeks [IQR, 34.6-38.1] v 39.4 weeks [IQR, 38.4-40.4]; P < 0.001) and they were
more likely to be large for gestational age (LGA) (adjusted odds ratio [aOR],
7.9; 95% CI, 5.3-11.8). Women with type 1 diabetes were more likely to have had
labour induced (aOR, 3.0; 95% CI, 2.0-4.5), a caesarean delivery (aOR, 4.6; 95%
CI, 3.1-7.0), or a pre-term birth (aOR, 6.7; 95% CI, 4.5-10.0); their babies were
more likely to have shoulder dystocia (aOR, 8.2; 95% CI, 3.6-18.7), hypoglycaemia
(aOR, 10.3; 95% CI, 6.8-15.6), jaundice (aOR, 5.1; 95% CI, 3.3-7.7), respiratory
distress (aOR, 2.5; 95% CI, 1.4-4.4) or to suffer perinatal death (aOR, 4.3; 95%
CI, 1.9-9.9). In women with type 1 diabetes, greater obesity was associated with
increased odds for an LGA baby or congenital malformation, and increased HbA1c
levels were associated with pre-term birth and perinatal death. CONCLUSION: Women
with type 1 diabetes, even when managed in a specialist setting, still experience
adverse obstetric and neonatal outcomes. Poor glycaemic control is not wholly
responsible for adverse outcomes, reinforcing the importance of other risk
factors, such as obesity and weight gain.
PMID- 27510346
TI - Low HIV testing rates among people with a sexually transmissible infection
diagnosis in remote Aboriginal communities.
AB - OBJECTIVE: To determine the rates of HIV testing among people who had received
positive test results for chlamydia, gonorrhoea and trichomoniasis, or who had
been tested for syphilis. DESIGN, SETTING AND PARTICIPANTS: Pathology data for
the period January 2010 - December 2014 from 65 remote Aboriginal communities
participating in the STRIVE trial of sexually transmissible infection (STI)
control were analysed. MAIN OUTCOME MEASURES: Rates of HIV testing within 30 and
90 days of an STI test (for chlamydia, gonorrhoea or trichomoniasis), the result
of which was positive, and within 30 days of a test for syphilis; factors
independently associated with concurrent HIV testing. RESULTS: 31.8% of 15 260
positive STI test results were linked with an HIV test within 30 days of the test
(including 5.6% not on the same day), and 34.8% within 90 days; 44.1% were linked
with syphilis testing within 30 days. 53.4% of all those tested for syphilis were
also tested for HIV within 30 days. Multivariate analysis found that HIV testing
was more likely for men, in geographical regions 3 and 4, in association with
positive STI test results during 2012, 2013 or 2014 (v 2010), and in association
with positive test results for gonorrhoea or chlamydia. Similar associations with
these factors were found for syphilis testing. CONCLUSIONS: A significant
challenge in Aboriginal health is avoiding an increase in the number of HIV
infections. One critical intervention in this regard is timely and appropriate
testing. Adhering to screening recommendations is clearly an aspect of the
delivery of sexual health services to remote communities that can be improved in
striving to achieve this aim.
PMID- 27510347
TI - Evaluation of the performance and outcomes for the first year of a diabetes rapid
access clinic.
PMID- 27510348
TI - Endocrine Society of Australia position statement on male hypogonadism (part 1):
assessment and indications for testosterone therapy.
AB - INTRODUCTION: This article, Part 1 of the Endocrine Society of Australia's
position statement on male hypogonadism, focuses on assessment of male
hypogonadism, including the indications for testosterone therapy. (Part 2 will
deal with treatment and therapeutic considerations.) MAIN RECOMMENDATIONS: Key
points and recommendations are:Pathological hypogonadism arises due to diseases
of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes
(hypergonadotropic hypogonadism). It is a clinical diagnosis with a pathological
basis, confirmed by hormone assays.Hormonal assessment is based on measurement of
circulating testosterone, luteinising hormone (LH) and follicle-stimulating
hormone (FSH) concentrations. Measurement of sex hormone-binding globulin levels
can be informative, but use of calculated free testosterone is not recommended
for clinical decision making.Testosterone replacement therapy is warranted in men
with pathological hypogonadism, regardless of age.Currently, there are limited
data from high-quality randomised controlled trials with clinically meaningful
outcomes to justify testosterone treatment in older men, usually with chronic
disease, who have low circulating testosterone levels but without hypothalamic,
pituitary or testicular disease.Obesity, metabolic syndrome and type 2 diabetes
are associated with lowering of circulating testosterone level, but without
elevation of LH and FSH levels. Whether these are non-specific consequences of
non-reproductive disorders or a correctable deficiency state is unknown, but
clear evidence for efficacy and safety of testosterone therapy in this setting is
lacking.Glucocorticoid and opioid use is associated with possibly reversible
reductions in circulating testosterone level, without elevation of LH and FSH
levels. Where continuation of glucocorticoid or opioid therapy is necessary,
review by an endocrinologist may be warranted.Changes in management as result of
the position statement: Men with pathological hypogonadism should be identified
and considered for testosterone therapy, while further research is needed to
clarify whether there is a role for testosterone in these other settings.
PMID- 27510349
TI - Managing thyroid disease in general practice.
AB - Serum thyroid-stimulating hormone (TSH) testing is the best screening tool for
thyroid dysfunction. When TSH levels are in the reference range, additional tests
such as free thyroxine, free triiodothyronine or thyroid antibodies rarely add
value, except in patients with pituitary disease, when TSH is unreliable. Overt
hypothyroidism and subclinical hypothyroidism with TSH levels > 10 mU/L can be
treated without further investigation. The health impact of subclinical
hypothyroidism with mildly elevated levels of TSH (4-10 mU/L) remains uncertain,
particularly in older people; treatment or observation are reasonable options.
Thyroxine remains standard treatment for hypothyroidism, with optimal dosage
determined by clinical response and serum TSH. Hyperthyroidism is commonly caused
by Graves' disease, thyroiditis or toxic nodular goitre. The cause should be
established before offering treatment. Radionuclide scanning is the imaging
modality of choice. Positive TSH-receptor antibodies indicate Graves' disease.
Thyroid ultrasound is indicated for assessment of palpable goitre and thyroid
nodules. It is not part of routine assessment of hyperthyroidism or
hypothyroidism. Overzealous use of ultrasound identifies clinically unimportant
thyroid nodules and can lead to overdiagnosis of thyroid cancer. For thyroid
nodules, the key investigation is ultrasound-guided fine needle aspiration
biopsy, depending on size and sonographic appearance. Biopsy should not be
performed routinely on small nodules < 1 cm. It remains controversial whether
pregnant women should be screened for thyroid disease. Reference intervals for
thyroid function tests during pregnancy are not well established, and it is
uncertain whether thyroxine treatment for pregnant women with serum TSH levels
between 2.5 and 4.0 mU/L is beneficial. Iodine supplementation is recommended
during pregnancy.
PMID- 27510350
TI - Osteoporosis treatment: a missed opportunity.
AB - Osteoporosis affects 1.2 million Australians and, in 2012, fractures due to
osteoporosis and osteopenia in Australians aged over 50 years cost $2.75 billion.
Even minor minimal trauma fractures are associated with increased morbidity and
mortality. Despite increasing therapeutic options for managing osteoporosis,
fewer than 20% of patients with a minimal trauma fracture are treated or
investigated for osteoporosis, so under-treatment is extremely common. Fracture
risk assessment is important for selecting patients who require specific anti
osteoporosis therapy. Post-menopausal osteoporosis is frequently due to an
imbalance in bone remodelling, with bone resorption exceeding bone formation.
Antiresorptive drugs reduce the number, activity and lifespan of osteoclasts, and
include bisphosphonates, oestrogen, selective oestrogen receptor-modulating
drugs, strontium ranelate, and the human monoclonal antibody denosumab.
Teriparatide is the only anabolic agent currently available that stimulates
osteoblast recruitment and activity; its antifracture efficacy for non-vertebral
fractures increases with the duration of therapy for up to 2 years when it is
associated with persisting increases in bone formation rate at the tissue level.
Newer anabolic agents are imminent and include an analogue of parathyroid hormone
related protein, abaloparatide, and a humanised monoclonal antibody to an
inhibitor of bone formation, romosozumab. Selection of anti-osteoporosis therapy
should be individualised to patients, and the duration of bisphosphonate therapy
has been covered in recent guidelines. The benefits of treatment far outweigh any
risks associated with long term treatment. General practitioners need to take up
the challenge imposed by osteoporosis and become champions of change to close the
evidence-treatment gap.
PMID- 27510351
TI - The Burns Registry of Australia and New Zealand: progressing the evidence base
for burn care.
PMID- 27510352
TI - The Burns Registry of Australia and New Zealand: progressing the evidence base
for burn care.
PMID- 27510353
TI - Lessons from the bedside: ketoacidosis and SGLT2 inhibitors.
PMID- 27510354
TI - A caution regarding high-dose biotin therapy: misdiagnosis of hyperthyroidism in
euthyroid patients.
PMID- 27510355
TI - Standard redox potentials, pKas, and hydricities of inorganic complexes under
electrochemical conditions and implications for CO2 reduction.
AB - We use computational chemistry to systematically study the thermodynamic
stabilities of protonated and reduced intermediate states for Ru(2,2'
bipyridine)3, Ru(1,10-phenanthroline)3, and Ru(phen)2(pyrido[3',4':5,6]
pyrazino[2,3-f][1,10]phenanthroline) in aqueous solutions. Following our previous
studies of aromatic N-heterocycle molecules, we report pKas, standard redox
potentials, and hydricities as well as computationally derived Pourbaix diagrams
that show which states would be thermodynamically stable at different conditions
of pH and applied potential. Locations of added electrons within ligands and
complexes after reductions are also shown with electron density difference plots.
As with other aromatic N-heterocycle molecules implicated in CO2 reduction, we
find that several of the boundary lines from the Pourbaix diagrams are in close
proximity to the thermodynamic redox potentials for CO2 electroreductions, making
them thermodynamically appropriate for energetically efficient hydrogen
shuttling.
PMID- 27510356
TI - Quantitative structure-property relationships of retention indices of some sulfur
organic compounds using random forest technique as a variable selection and
modeling method.
AB - In this work, a noble quantitative structure-property relationship technique is
proposed on the basis of the random forest for prediction of the retention
indices of some sulfur organic compounds. In order to calculate the retention
indices of these compounds, the theoretical descriptors produced using their
molecular structures are employed. The influence of the significant parameters
affecting the capability of the developed random forest prediction power such as
the number of randomly selected variables applied to split each node (m) and the
number of trees (nt ) is studied to obtain the best model. After optimizing the
nt and m parameters, the random forest model conducted for m = 70 and nt = 460
was found to yield the best results. The artificial neural network and multiple
linear regression modeling techniques are also used to predict the retention
index values for these compounds for comparison with the results of random forest
model. The descriptors selected by the stepwise regression and random forest
model are used to build the artificial neural network models. The results
achieved showed the superiority of the random forest model over the other models
for prediction of the retention indices of the studied compounds.
PMID- 27510357
TI - Octahedral Tin Dioxide Nanocrystals Anchored on Vertically Aligned Carbon
Aerogels as High Capacity Anode Materials for Lithium-Ion Batteries.
AB - A novel binder-free graphene - carbon nanotubes - SnO2 (GCNT-SnO2) aerogel with
vertically aligned pores was prepared via a simple and efficient directional
freezing method. SnO2 octahedrons exposed of {221} high energy facets were
uniformly distributed and tightly anchored on multidimensional graphene/carbon
nanotube (GCNT) composites. Vertically aligned pores can effectively prevent the
emersion of "closed" pores which cannot load the active SnO2 nanoparticles,
further ensure quick immersion of electrolyte throughout the aerogel, and can
largely shorten the transport distance between lithium ions and active sites of
SnO2. Especially, excellent electrical conductivity of GCNT-SnO2 aerogel was
achieved as a result of good interconnected networks of graphene and CNTs.
Furthermore, meso- and macroporous structures with large surface area created by
the vertically aligned pores can provide great benefit to the favorable transport
kinetics for both lithium ion and electrons and afford sufficient space for
volume expansion of SnO2. Due to the well-designed architecture of GCNT-SnO2
aerogel, a high specific capacity of 1190 mAh/g with good long-term cycling
stability up to 1000 times was achieved. This work provides a promising strategy
for preparing free-standing and binder-free active electrode materials with high
performance for lithium ion batteries and other energy storage devices.
PMID- 27510358
TI - Delays in diagnosis and treatment of childhood cancer in Indonesia.
AB - BACKGROUND: Emphasizing timely diagnosis and treatment of cancer are important
themes in pediatric cancer management, as delays adversely impact survival. This
study explores various delay types among children with cancer and determines
factors that influence delays. METHODS: This cross-sectional study was conducted
at an Indonesian academic hospital. Parents of newly diagnosed patients were
interviewed between October 2013 and September 2014 using semistructured
questionnaires. Patient, physician, diagnosis, treatment, healthcare system
(HCS), and total delay were analyzed. RESULTS: Parents of 145 children (response
rate 89%) with cancer were interviewed. Median total delay was 70 days (range 5
4,055). Patient delay (median 5 days, range 0-189) was significantly shorter than
HCS delay (median 49 days, range 4-4,025, P < 0.001). Diagnosis delay (median 58
days, range 3-4,015) was significantly longer than treatment delay (median 3
days, range 1-89, P < 0.001). Older age at diagnosis significantly lengthened
patient delay (P = 0.044). Using alternative treatment was associated with
significantly longer patient and total delay (P = 0.025, 0.024, respectively).
Cancer type significantly influenced physician, diagnosis, treatment, HCS, and
total delay (P = 0.001, P = 0.004, P < 0.001, P < 0.001, P < 0.001,
respectively). Neurological tumors had the longest delays, whereas hematological
tumors had the shortest. Sex, parents' education or income level, disease stage
at diagnosis, health insurance status, distance from hospital, and first attended
health-facility type did not significantly impact the length of any delay type.
CONCLUSIONS: Healthcare providers need training to improve recognition of cancer
symptoms and speed up subsequent diagnostic processes. Using alternative
treatment increased patient and total delays. Community campaigns to encourage
families to seek conventional cancer treatments are recommended.
PMID- 27510359
TI - Chiral supramolecular polymers consisting of planar-chiral pillar[5]arene
enantiomers.
AB - Supramolecular polymers with diverse chiralities were constructed by
supramolecular polymerization of planar-chiral host-guest conjugates in pS and pR
forms. Hetero-chiral supramolecular polymerization using a racemic mixture of
host-guest conjugates with pS and pR forms afforded a supramolecular polymer with
a larger hydrodynamic radius than that obtained through homo-chiral
supramolecular polymerization of host-guest conjugates with either pS or pR forms
alone.
PMID- 27510360
TI - Seeking for the links between biochemical markers of remodeling and structural
changes in chronic obstructive pulmonary disease: where are we?
PMID- 27510361
TI - Dynamic CT myocardial perfusion imaging.
AB - Non-invasive cardiac imaging has rapidly evolved during the last decade due to
advancements in CT based technologies. Coronary CT angiography has been shown to
reliably assess coronary anatomy and detect high risk coronary artery disease.
However, this technique is limited to anatomical assessment, thus non-invasive
techniques for functional assessment of the heart are necessary. CT myocardial
perfusion is a new CT based technique that provides functional assessment of the
myocardium and allows for a comprehensive assessment of coronary artery disease
with a single modality when combined with CTA. This review aims to discuss
dynamic CT myocardial perfusion as a new technique in the assessment of CAD.
PMID- 27510362
TI - An Agrobacterium-delivered CRISPR/Cas9 system for high-frequency targeted
mutagenesis in maize.
AB - CRISPR/Cas9 is a powerful genome editing tool in many organisms, including a
number of monocots and dicots. Although the design and application of CRISPR/Cas9
is simpler compared to other nuclease-based genome editing tools, optimization
requires the consideration of the DNA delivery and tissue regeneration methods
for a particular species to achieve accuracy and efficiency. Here, we describe a
public sector system, ISU Maize CRISPR, utilizing Agrobacterium-delivered
CRISPR/Cas9 for high-frequency targeted mutagenesis in maize. This system
consists of an Escherichia coli cloning vector and an Agrobacterium binary
vector. It can be used to clone up to four guide RNAs for single or multiplex
gene targeting. We evaluated this system for its mutagenesis frequency and
heritability using four maize genes in two duplicated pairs: Argonaute 18
(ZmAgo18a and ZmAgo18b) and dihydroflavonol 4-reductase or anthocyaninless genes
(a1 and a4). T0 transgenic events carrying mono- or diallelic mutations of one
locus and various combinations of allelic mutations of two loci occurred at rates
over 70% mutants per transgenic events in both Hi-II and B104 genotypes. Through
genetic segregation, null segregants carrying only the desired mutant alleles
without the CRISPR transgene could be generated in T1 progeny. Inheritance of an
active CRISPR/Cas9 transgene leads to additional target-specific mutations in
subsequent generations. Duplex infection of immature embryos by mixing two
individual Agrobacterium strains harbouring different Cas9/gRNA modules can be
performed for improved cost efficiency. Together, the findings demonstrate that
the ISU Maize CRISPR platform is an effective and robust tool to targeted
mutagenesis in maize.
PMID- 27510367
TI - Allometric Scaling of Clearance in Paediatric Patients: When Does the Magic of
0.75 Fade?
AB - Allometric scaling on the basis of bodyweight raised to the power of 0.75
(AS0.75) is frequently used to scale size-related changes in plasma clearance
(CLp) from adults to children. A systematic assessment of its applicability is
undertaken for scenarios considering size-related changes with and without
maturation processes. A physiologically-based pharmacokinetic (PBPK) simulation
workflow was developed in R for 12,620 hypothetical drugs. In scenario one, only
size-related changes in liver weight, hepatic blood flow, and glomerular
filtration were included in simulations of 'true' paediatric CLp. In a second
scenario, maturation in unbound microsomal intrinsic clearance (CLint,mic),
plasma protein concentration, and haematocrit were also included in these
simulated 'true' paediatric CLp values. For both scenarios, the prediction error
(PE) of AS0.75-based paediatric CLp predictions was assessed, while, for the
first scenario, an allometric exponent was also estimated based on 'true' CLp. In
the first scenario, the PE of AS0.75-based paediatric CLp predictions reached up
to 278 % in neonates, and the allometric exponent was estimated to range from
0.50 to 1.20 depending on age and drug properties. In the second scenario, the PE
sensitivity to drug properties and maturation was higher in the youngest
children, with AS0.75 resulting in accurate CLp predictions above 5 years of age.
Using PBPK principles, there is no evidence for one unique allometric exponent in
paediatric patients, even in scenarios that only consider size-related changes.
As PE is most sensitive to the allometric exponent, drug properties and
maturation in younger children, AS0.75 leads to increasingly worse predictions
with decreasing age.
PMID- 27510368
TI - Overexpression of long non-coding RNA NR_036575.1 contributes to the
proliferation and migration of papillary thyroid cancer.
AB - Current evidence suggests that the human genome produces a large number of non
coding RNAs, including microRNAs and long non-coding RNAs (lncRNAs). Generally,
lncRNAs are defined as RNA transcripts longer than 200 nucleotides that are not
transcribed into proteins. In recent years, lncRNAs have been reported to play
oncogenic roles in tumourigenesis. However, minimal research has been performed
on the expression and clinicopathological significance of lncRNAs in papillary
thyroid cancer (PTC). In the present study, we investigated not only the
expression and clinicopathological significance of a novel lncRNA, NR_036575.1,
in PTC tissues and adjacent non-cancerous tissues but also its potential function
in TPC1 cells. The expression levels of the lncRNA NR_036575.1 in 83 pairs of PTC
tissues and adjacent non-cancerous tissues were detected via quantitative real
time polymerase chain reaction. The relationships between the expression levels
and clinicopathological characteristics of the lncRNA NR_036575.1 were analysed.
In addition, we established two receiver operating characteristic (ROC) curves to
assess the diagnostic value of NR_036575.1 expression. Cell Counting Kit-8 and
transwell assays were used to assess cell proliferation and migration,
respectively. The expression levels of the lncRNA NR_036575.1 were significantly
higher in PTC tissues than in adjacent non-cancerous tissues. High NR_036575.1
expression was associated with extrathyroidal extension (ETE) (P = 0.011) and
tumour size (P = 0.006). The ROC curves indicated that NR_036575.1 could
potentially serve as a biomarker for identifying PTC and related, non-cancerous
diseases (sensitivity, 80.7 %; specificity, 88 %), as well as for differentiating
between PTC with or without ETE (sensitivity, 57.8 %; specificity, 86.7 %).
NR_036575.1 knock-down significantly inhibited the proliferation and migration of
TPC1 cells. Our findings are the first to describe lncRNA NR_036575.1
overexpression in PTC. NR_036575.1 expression was associated with both ETE and
tumour size. In addition, NR_036575.1 modulation could regulate TPC1 cell
proliferation and migration. The results of our study suggest that NR_036575.1
could be applied as a potential biomarker and a novel therapeutic target for PTC
patients.
PMID- 27510369
TI - Quantum measurement-induced antiferromagnetic order and density modulations in
ultracold Fermi gases in optical lattices.
AB - Ultracold atomic systems offer a unique tool for understanding behavior of matter
in the quantum degenerate regime, promising studies of a vast range of phenomena
covering many disciplines from condensed matter to quantum information and
particle physics. Coupling these systems to quantized light fields opens further
possibilities of observing delicate effects typical of quantum optics in the
context of strongly correlated systems. Measurement backaction is one of the most
funda- mental manifestations of quantum mechanics and it is at the core of many
famous quantum optics experiments. Here we show that quantum backaction of weak
measurement can be used for tailoring long-range correlations of ultracold
fermions, realizing quantum states with spatial modulations of the density and
magnetization, thus overcoming usual requirement for a strong interatomic
interactions. We propose detection schemes for implementing antiferromagnetic
states and density waves. We demonstrate that such long-range correlations cannot
be realized with local addressing, and they are a consequence of the competition
between global but spatially structured backaction of weak quantum measurement
and unitary dynamics of fermions.
PMID- 27510370
TI - Inferential tools in penalized logistic regression for small and sparse data: A
comparative study.
AB - This paper focuses on inferential tools in the logistic regression model fitted
by the Firth penalized likelihood. In this context, the Likelihood Ratio
statistic is often reported to be the preferred choice as compared to the
'traditional' Wald statistic. In this work, we consider and discuss a wider range
of test statistics, including the robust Wald, the Score, and the recently
proposed Gradient statistic. We compare all these asymptotically equivalent
statistics in terms of interval estimation and hypothesis testing via simulation
experiments and analyses of two real datasets. We find out that the Likelihood
Ratio statistic does not appear the best inferential device in the Firth
penalized logistic regression.
PMID- 27510372
TI - Parsimonious mixtures of multivariate contaminated normal distributions.
AB - A mixture of multivariate contaminated normal distributions is developed for
model-based clustering. In addition to the parameters of the classical normal
mixture, our contaminated mixture has, for each cluster, a parameter controlling
the proportion of mild outliers and one specifying the degree of contamination.
Crucially, these parameters do not have to be specified a priori, adding a
flexibility to our approach. Parsimony is introduced via eigen-decomposition of
the component covariance matrices, and sufficient conditions for the
identifiability of all the members of the resulting family are provided. An
expectation-conditional maximization algorithm is outlined for parameter
estimation and various implementation issues are discussed. Using a large-scale
simulation study, the behavior of the proposed approach is investigated and
comparison with well-established finite mixtures is provided. The performance of
this novel family of models is also illustrated on artificial and real data.
PMID- 27510371
TI - Mms21 SUMO Ligase Activity Promotes Nucleolar Function in Saccharomyces
cerevisiae.
AB - The budding yeast E3 SUMO ligase Mms21, also known as Nse2, is a component of the
Smc5/6 complex, which regulates sister chromatid cohesion, DNA replication, and
repair. Our study shows that the mms21RINGDelta mutant exhibits (1) reduced
ribosomal RNA production; (2) nuclear accumulation of ribosomal proteins; (3)
elevated Gcn4 translation, indicating translational stress; and (4) upregulation
of Gcn4 targets. Genes involved in ribosome biogenesis and translation are
downregulated in the mms21RINGDelta mutant. We identified RPL19A as a novel
genetic suppressor of the mms21RINGDelta mutant. Deletion of RPL19A partially
suppresses growth defects in both smc5-6 and mms21RINGDelta mutants as well as
nuclear accumulation of ribosome subunits in the mms21RINGDelta mutant. Deletion
of a previously identified strong suppressor, MPH1, rescues both the accumulation
of ribosome subunits and translational stress. This study suggests that the
Smc5/6 complex supports nucleolar function.
PMID- 27510373
TI - Accuracy of teledentistry examinations at predicting actual treatment modality in
a pediatric dentistry clinic.
AB - Objectives The purpose of this study was to assess the accuracy of predicting
dental treatment modalities for children seen initially by means of a live-video
teledentistry consultation. Methods A retrospective dental record review was
completed of 251 rural pediatric patients from the Finger Lakes region of New
York State who had an initial teledentistry appointment with a board-certified
pediatric dentist located remotely at the Eastman Institute for Oral Health in
Rochester, NY. Proportions of children who were referred for specific treatment
modalities and who completed treatment and proportions of children for whom the
treatment recommendation was changed were calculated. Fisher's exact test was
used to assess statistical significance. Results The initial treatment modality
was not changed for 221/251 (88%) children initially seen for a teledentistry
consultation. Thirty (12%) children had the initial treatment modality changed,
most frequently children who were initially suggested treatment with nitrous
oxide. Based on the initial treatment modality, changes to a different treatment
modality were statistically significant (Fisher's exact test, p < 0.0001).
Conclusions Our data suggest that the use of a live-video teledentistry
consultation can be an effective way of predicting the best treatment modality
for rural children with significant dental disease. A live-video teledentistry
consultation can be an effective intervention to facilitate completion of complex
treatment plans for children from a rural area that have extensive dental needs.
PMID- 27510374
TI - Margaret McCartney: Game on for Pokemon Go.
PMID- 27510375
TI - A Case of Spontaneous Isolated Dissection of Left Gastric Artery.
PMID- 27510376
TI - Statement on Publication Ethics for Editors and Publishers.
AB - The digitization and related developments in journal editing and publishing
necessitate increasing the awareness of all stakeholders of science communication
in the emerging global problems and possible solutions. Journal editors and
publishers are frequently encountered with the fast-growing problems of
authorship, conflicts of interest, peer review, research misconduct, unethical
citations, and inappropriate journal impact metrics. While the number of
erroneous and unethical research papers and wasteful, or 'predatory', journals is
increasing exponentially, responsible editors are urged to 'clean' the literature
by correcting or retracting related articles. Indexers are advised to implement
measures for accepting truly influential and ethical journals and delisting
sources with predatory publishing practices. Updating knowledge and skills of
authors, editors and publishers, developing and endorsing recommendations of
global editorial associations, and (re)drafting journal instructions can be
viewed as potential tools for improving ethics of academic journals. The aim of
this Statement is to increase awareness of all stakeholders of science
communication of the emerging ethical issues in journal editing and publishing
and initiate a campaign of upgrading and enforcing related journal instructions.
PMID- 27510378
TI - Affecting Factors of Secondhand Smoke Exposure in Korea: Focused on Different
Exposure Locations.
AB - Exposure to secondhand smoke (SHS) not only can cause serious illness, but is
also an economic and social burden. Contextual and individual factors of non
smoker exposure to SHS depend on location. However, studies focusing on this
subject are lacking. In this study, we described and compared the factors related
to SHS exposure according to location in Korea. Regarding individual factors
related to SHS exposure, a common individual variable model and location-specific
variable model was used to evaluate SHS exposure at home/work/public locations
based on sex. In common individual variables, such as age, and smoking status
showed different relationships with SHS exposure in different locations. Among
home-related variables, housing type and family with a single father and
unmarried children showed the strongest positive relationships with SHS exposure
in both males and females. In the workplace, service and sales workers, blue
collar workers, and manual laborers showed the strongest positive association
with SHS exposure in males and females. For multilevel analysis in public places,
only SHS exposure in females was positively related with cancer screening rate.
Exposure to SHS in public places showed a positive relationship with drinking
rate and single-parent family in males and females. The problem of SHS embodies
social policies and interactions between individuals and social contextual
factors. Policy makers should consider the contextual factors of specific
locations and regional and individual context, along with differences between
males and females, to develop effective strategies for reducing SHS exposure.
PMID- 27510377
TI - Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse
Event Reporting System Database.
AB - We conducted pharmacovigilance data mining for a beta-lactam antibiotics,
amoxicillin, and compare the adverse events (AEs) with the drug labels of 9
countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and
Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a
nationwide database of AE reports, between December 1988 and June 2014.
Frequentist and Bayesian methods were used to calculate disproportionality
distribution of drug-AE pairs. The AE which was detected by all the three indices
of proportional reporting ratio (PRR), reporting odds ratio (ROR), and
information component (IC) was defined as a signal. The KAERS database contained
a total of 807,582 AE reports, among which 1,722 reports were attributed to
amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE
pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin
signals. Comparing the drug labels of 9 countries, 12 adverse events including
ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth,
gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal
crying, induration, pulmonary carcinoma, and influenza-like symptoms were not
listed on any of the labels of nine countries. In conclusion, we detected 12 new
signals of amoxicillin which were not listed on the labels of 9 countries.
Therefore, it should be followed by signal evaluation including causal
association, clinical significance, and preventability.
PMID- 27510379
TI - Transplantation of Mesenchymal Stem Cells for Acute Spinal Cord Injury in Rats:
Comparative Study between Intralesional Injection and Scaffold Based
Transplantation.
AB - Experimental stem cell therapy for spinal cord injury (SCI) has been extensively
investigated. The selection of effective cell transplantation route is also an
important issue. Although various types of scaffold have been widely tried as a
carrier of stem cells to the injured spinal cord, there was little comparative
study to investigate the efficacy of transplantation comparing with conventional
transplantation route. A total of 48 Sprague-Dawley rats were subjected to
standardized SCI, followed by transplantation of allogeneic mesenchymal stem
cells (MSCs), either via intralesional injection (IL group), or via the poly
(lactic-co-glycolic acid) (PLGA) scaffold (IP group) or chitosan scaffold (IC
group). Engraftment and differentiation of the transplanted cells, expression of
neurotrophic factors in the injured spinal cord, and functional recovery were
compared with those of the control group. The mean numbers of engrafted MSCs in
the IL, IP, and IC groups were 20.6 +/- 0.7, 25.6 +/- 1.7 and 26.7 +/- 1.8
cells/high power filed (HPF), respectively. Results showed higher success rate of
MSCs engraftment in the scaffold groups compared to the IL group. Expression of
neuroprotective growth factors in the SCI lesions showed no significant
differences between the IL, IP, and IC groups. The mean Basso, Beattie and
Bresnahan locomotor scales at 6 weeks post-transplantation in the IL, IP, IC, and
control groups were 7.9 +/- 1.1, 7.9 +/- 2.1, 8.7 +/- 2.1, and 2.9 +/- 1.0,
respectively. The functional improvement was most excellent in the IC group. The
scaffold based MSC transplantation for acute SCI presented the better cell
engraftment and neuroprotective effect compared to the intralesional injection
transplantation.
PMID- 27510381
TI - Detection of MYCN Amplification in Serum DNA Using Conventional Polymerase Chain
Reaction.
AB - Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and
is characterized by a wide range of clinical behaviors. Amplification of MYCN is
a well-known poor prognostic factor in NB patients. As the MYCN amplification
status is usually tested using tumor specimens, lengthy and invasive procedures
are unavoidable. To evaluate the possibility of detecting MYCN amplification
without invasive procedure, we performed conventional polymerase chain reaction
(PCR) analysis to identify MYCN amplification using the preserved serum DNA. PCR
of serum DNA was done in 105 NB patients whose MYCN status had been confirmed by
fluorescence in situ hybridization. MYCN amplification was evaluated as the ratio
of signal intensities between MYCN and NAGK (M/N ratio). When regarding the
tissue FISH results as a reference, 10 patients had MYCN-amplified (MNA) NB, and
95 had non-MNA NB. The M/N ratio of the MNA group (median 2.56, range 1.01-3.58)
was significantly higher than that of the non-MNA group (median 0.97, range 0.67
5.18) (P < 0.001). In the receiver operating characteristic curve analysis, the
area under the curve was 0.957 (95% confidence interval 0.898-1.000; P < 0.001),
and it showed 90.9% sensitivity and 97.9% specificity with the selected cut-off
value set as 1.6. The detection of MYCN amplification using conventional PCR
analysis of serum samples seems to be a simple and promising method to evaluate
the MYCN status of NB patients. Further study with a larger set of patients is
needed to confirm the accuracy of this result.
PMID- 27510382
TI - Complications of Cardiac Perforation and Lead Dislodgement with an MRI
Conditional Pacing Lead: a Korean Multi-Center Experience.
AB - Medtronic CapSureFix MRI 5086 pacing lead (5086; Medtronic, Inc., Minneapolis,
MN, USA) has been reported to be associated with increased cardiac perforation
and lead dislodgement. This study aimed to compare the incidence of cardiac
perforation and lead dislodgement within 30 days after pacemaker implantation
between 5086 MRI lead and previous Medtronic CapSureFix Novus 5076 non-MRI pacing
lead. This was a nationwide, multicenter retrospective study in which we compared
the incidence of adverse events between 277 patients implanted with 5086 lead and
205 patients implanted with 5076 lead between March 2009 and September 2014.
Cardiac perforation within 30 days of pacemaker implantation occurred in 4
patients (1.4%) with the 5086 lead and in no patient with the 5076 lead (P =
0.084). Lead dislodgement occurred in 8 patients (2.9%) with the 5086 lead and in
5 patients (2.4%) with the 5076 lead (P = 0.764). On multivariate logistic
regression analysis, age was significantly associated with cardiac perforation.
Congestive heart failure and implantation of right atrial (RA) lead at RA free
wall or septum were significant factors for the incidence of lead dislodgement
and lead revision. The incidence of cardiac perforation and lead dislodgement
were not statistically different between the patients with 5086 lead and the
patients with 5076 lead. However, careful attention for cardiac perforation may
be needed when using the 5086 MRI lead, especially in elderly patients.
PMID- 27510380
TI - The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with
Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in
South Korean Infants.
AB - Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines
administered as separate injections. In this randomized, open, controlled study
we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent
combination vaccine (PentaximTM) compared with licensed DTaP-IPV and Hib (PRP~T)
vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP
IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine
at 2, 4, 6 months of age. Antibodies to all components were measured before the
first vaccination and one month after the third, and safety was assessed after
each vaccination including recording of reactions by parents. We confirmed the
non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of
both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0%
demonstrated seroresponses to pertussis antigens. Antibody levels were similar in
both groups, except for those to the Hib component, PRP~T. In separate and
combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9
and 11.0 MUg/mL, respectively, but 98.3% and 97.4% had titers >= 1 MUg/mL,
indicative of long-term protection. All vaccines were well tolerated, with no
vaccine-related serious adverse event. Both groups had similar safety profiles,
but the combined vaccine group had fewer injection site reactions. The
immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine
to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and
injection site reactions, supports the licensure and incorporation of DTaP
IPV//Hib into the Korean national vaccination schedule (Clinical trial registry,
NCT01214889).
PMID- 27510384
TI - Association between Growth Differentiation Factor 15 (GDF15) and Cardiovascular
Risk in Patients with Newly Diagnosed Type 2 Diabetes Mellitus.
AB - We investigated an association between serum Growth Differentiation Factor 15
(GDF15) level and cardiovascular risk in patients with newly diagnosed type 2
diabetes mellitus (T2D). A total of 107 participants were screened for T2D and
divided into a T2D group and a control group (without diabetes). We used the
Framingham risk score (FRS) and the New Pooled Cohort Equation score to estimate
the 10-year risk of atherosclerotic cardiovascular disease. Serum GDF15 levels
were measured using an enzyme-linked immunosorbent assay. Correlation analyses
were performed to evaluate the associations between GDF15 level and
cardiovascular risk scores. The mean serum GDF15 level was elevated in the T2D
group compared to the control group (P < 0.001). A positive correlation was
evident between serum GDF15 level and age (r = 0.418, P = 0.001), the FRS (r =
0.457, P < 0.001), and the Pooled Cohort Equation score (r = 0.539, P < 0.001).
After adjusting for age, LDL-C level, and body mass index (BMI), the serum GDF15
level was positively correlated with the FRS and the New Pooled Cohort Equation
score. The serum GDF15 level is independently associated with cardiovascular risk
scores of newly diagnosed T2D patients. This suggests that the level of GDF15 may
be a useful predictive biomarker of cardiovascular risk in newly diagnosed T2D
patients.
PMID- 27510383
TI - Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in
a Mouse Model of Adriamycin-induced Nephropathy.
AB - The concentration of adenosine in the normal kidney increases markedly during
renal hypoxia, ischemia, and inflammation. A recent study reported that an A3
adenosine receptor (A3AR) antagonist attenuated the progression of renal
fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury,
which results in severe proteinuria and progressive glomerulosclerosis. In this
study, we investigated the preventive effect of a highly selective A3AR
antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old
Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg)
for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX
treatment decreased body weight without a change in water and food intake, but
this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma
creatinine level, proteinuria, and albuminuria, which had increased during ADX
treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte
injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration,
which are markers of oxidative stress, increased after injection of ADX. ADX also
induced the activation of proinflammatory and profibrotic molecules such as TGF
beta1, MCP-1, PAI-1, type IV collagen, NF-kappaB, NOX4, TLR4, TNFalpha, IL-1beta,
and IFN-gamma, but they were remarkably suppressed after LJ1888 treatment. In
conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX
induced nephropathy, which might be associated with podocyte injury through
oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be
considered as a potential therapeutic agent in renal glomerular diseases which
include podocyte injury and proteinuria.
PMID- 27510385
TI - Metformin Reduces Bleomycin-induced Pulmonary Fibrosis in Mice.
AB - Metformin has anti-inflammatory and anti-fibrotic effects. We investigated
whether metformin has an inhibitory effect on bleomycin (BLM)-induced pulmonary
fibrosis in a murine model. A total of 62 mice were divided into 5 groups:
control, metformin (100 mg/kg), BLM, and BLM with metformin (50 mg/kg or 100
mg/kg). Metformin was administered to the mice orally once a day from day 1. We
sacrificed half of the mice on day 10 and collected the bronchoalveolar lavage
fluid (BALF) from their left lungs. The remaining mice were sacrificed and
analyzed on day 21. The right lungs were harvested for histological analyses. The
messenger RNA (mRNA) levels of epithelial-mesenchymal transition markers were
determined via analysis of the harvested lungs on day 21. The mice treated with
BLM and metformin (50 mg/kg or 100 mg/kg) showed significantly lower levels of
inflammatory cells in the BALF compared with the BLM-only mice on days 10 and 21.
The histological examination revealed that the metformin treatment led to a
greater reduction in inflammation than the treatment with BLM alone. The mRNA
levels of collagen, collagen-1, procollagen, fibronectin, and transforming growth
factor-beta in the metformin-treated mice were lower than those in the BLM-only
mice on day 21, although statistical significance was observed only in the case
of procollagen due to the small number of live mice in the BLM-only group.
Additionally, treatment with metformin reduced fibrosis to a greater extent than
treatment with BLM alone. Metformin suppresses the inflammatory and fibrotic
processes of BLM-induced pulmonary fibrosis in a murine model.
PMID- 27510386
TI - Risk Factors of Advanced Adenoma in Small and Diminutive Colorectal Polyp.
AB - The aims of this study were to review the clinicopathological characteristics of
diminutive (<= 5 mm) and small polyps (> 5 mm but < 10 mm) and to evaluate the
risk factors of advanced adenoma for polyps of diameter < 10 mm in the colon. The
medical records of 4,711 patients who underwent first colonoscopy at outpatient
clinics or health promotion center were reviewed retrospectively. We analyzed the
presence and risk factors of advanced adenoma, which was defined as a villous or
tubulovillous polyp, high-grade dysplasia or intramucosal carcinoma
histologically. Total 5,058 polyps were detected in the 4,711 patients, and 93.0%
(4,704/5,058) polyps were < 10 mm in size. Among them, advanced adenoma was noted
in 0.6% (28/4,704) with a villous component in 19, high-grade dysplasia in 3, and
adenocarcinoma in 6. Advanced and non-advanced adenomas differed significantly in
age group, gender, and polyp size. Multivariate analysis showed that an advanced
age (> 65 years), a male gender, and a polyp size of > 5 mm were risk factors of
advanced adenoma. The incidence of advanced adenoma in polyps of < 10 mm was
0.6%. Polyp size, male gender, and age of > 65 years are independent risk factors
of advanced adenoma.
PMID- 27510387
TI - Clinical Utility of a New Automated Hepatitis C Virus Core Antigen Assay for
Prediction of Treatment Response in Patients with Chronic Hepatitis C.
AB - Hepatitis C virus core antigen (HCV Ag) is a recently developed marker of
hepatitis C virus (HCV) infection. We investigated the clinical utility of the
new HCV Ag assay for prediction of treatment response in HCV infection. We
analyzed serum from 92 patients with HCV infection who had been treated with
pegylated interferon and ribavirin. HCV Ag levels were determined at baseline in
all enrolled patients and at week 4 in 15 patients. Baseline HCV Ag levels showed
good correlations with HCV RNA (r = 0.79, P < 0.001). Mean HCV Ag levels at
baseline were significantly lower in patients with a sustained virologic response
(SVR) than in those with a non SVR (relapse plus non responder) based on HCV RNA
analysis (2.8 log10fmol/L vs. 3.27 log10fmol/L, P = 0.023). Monitoring of the
viral kinetics by determination of HCV RNA and HCV Ag levels resulted in
similarly shaped curves. Patients with undetectable HCV Ag levels at week 4 had a
92.3% probability of achieving SVR based on HCV RNA assay results. The HCV Ag
assay may be used as a supplement for predicting treatment response in HCV
infection, but not as an alternative to the HCV RNA assay.
PMID- 27510388
TI - Development of a Swine Benign Biliary Stricture Model Using Endoscopic Biliary
Radiofrequency Ablation.
AB - The large animal model with benign biliary stricture (BBS) is essential to
undergo experiment on developing new devices and endoscopic treatment. This study
conducted to establish a clinically relevant porcine BBS model by means of
endobiliary radiofrequency ablation (RFA). Endoscopic retrograde cholangiography
(ERC) was performed on 12 swine. The animals were allocated to three groups (60,
80, and 100 W) according to the electrical power level of RFA electrode.
Endobiliary RFA was applied to the common bile duct for 60 seconds using an RFA
catheter that was endoscopically inserted. ERC was repeated two and four weeks,
respectively, after the RFA to identify BBS. After the strictures were
identified, histologic evaluations were performed. On the follow-up ERC two weeks
after the procedure, a segmental bile duct stricture was observed in all animals.
On microscopic examination, severe periductal fibrosis and luminal obliteration
with transmural inflammation were demonstrated. Bile duct perforations occurred
in two pigs (100 W, n = 1; 80 W, n = 1) but there were no major complications in
the 60 W group. The application of endobiliary RFA with 60 W electrical power
resulted in a safe and reproducible swine model of BBS.
PMID- 27510389
TI - Epidemiologic Study on Kawasaki Disease in Korea, 2007-2014: Based on Health
Insurance Review & Assessment Service Claims.
AB - The aim of this study is to assess the actual epidemiologic features of Kawasaki
disease (KD) in Korea using the data from Health Insurance Review & Assessment
Service (HIRA) claims from 2007 to 2014. We investigated HIRA claims of patients
who had KD (International Classification of Diseases-10, M30.3) as a major
diagnosis and were given intravenous immunoglobulin (IVIG) from 2007 to 2014. A
total of 39,082 patients were reported during the period. The male-to-female
ratio was 1.42 and the median age was 28 months. The incidence rates were 168.3
per 100,000 population aged 0 to 4 years in 2007, 159.1 in 2008, 167.3 in 2009,
190.4 in 2010, 188.2 in 2011, 190.2 in 2012, 210.4 in 2013 and 217.2 in 2014.
These rates were much higher than those in the previous studies in Korea. KD
occurred more often in early summer (May, June and July) and winter (December and
January). The annual incidence rate of KD had been increasing every year,
reaching 217.2 per 100,000 population aged 0 to 4 years in 2014. It is the second
highest incidence rate of KD in the world after Japan.
PMID- 27510390
TI - Neonatal and Infant Mortality in Korea, Japan, and the U.S.: Effect of Birth
Weight Distribution and Birth Weight-Specific Mortality Rates.
AB - Difference in crude neonatal and infant mortality rates (NMR and IMR) among
different countries is due to the differences in its two determinants: birth
weight distribution (BWD) and birth weight-specific mortality rates (BW-SMRs). We
aimed to determine impact of BWD and BW-SMRs on differences in crude NMR and IMR
among Korea, Japan, and the U.S. Our study used the live birth data of the period
2009 through 2010. Crude NMR/IMR are the lowest in Japan, 1.1/2.1, compared to
1.8/3.2, in Korea, and 4.1/6.2, in the U.S., respectively. Japanese had the best
BW-SMRs of all birth weight groups compared to the Koreans and the U.S. The U.S.
BWD was unfavorable with very low birth weight (< 1,500 g) rate of 1.4%, compared
to 0.6% in Korea, and 0.8% in Japan. If Koreans and Japanese had the same BWD as
in the U.S., their crude NMR/IMR would be 3.9/6.1 for the Koreans and 1.5/2.5 for
the Japanese. If both Koreans and Japanese had the same BW-SMRs as in the U.S.,
the crude NMR/IMR would be 2.0/3.8 for the Koreans and 2.7/5.0 for the Japanese.
In conclusion, compared to the U.S., lower crude NMR or IMR in Japan is mainly
attributable to its better BW-SMRs. Koreans had lower crude NMR and IMR,
primarily from its favorable BWD. Comparing crude NMR or IMR among different
countries should include further exploration of its two determinants, BW-SMRs
reflecting medical care, and BWD reflecting socio-demographic conditions.
PMID- 27510391
TI - Ten Triangles around Cavernous Sinus for Surgical Approach, Described by
Schematic Diagram and Three Dimensional Models with the Sectioned Images.
AB - For the surgical approach to lesions around the cavernous sinus (CS), triangular
spaces around CS have been devised. However, educational materials for learning
the triangles were insufficient. The purpose of this study is to present
educational materials about the triangles, consisting of a schematic diagram and
3-dimensional (3D) models with sectioned images. To achieve the purposes, other
studies were analyzed to establish new definitions and names of the triangular
spaces. Learning materials including schematic diagrams and 3D models with
cadaver's sectioned images were manufactured. Our new definition was attested by
observing the sectioned images and 3D models. The triangles and the four
representative surgical approaches were stereoscopically indicated on the 3D
models. All materials of this study were put into Portable Document Format file
and were distributed freely at our homepage (anatomy.dongguk.ac.kr/triangles). By
using our schematic diagram and the 3D models with sectioned images, ten
triangles and the related structures could be understood and observed accurately.
We expect that our data will contribute to anatomy education, surgery training,
and radiologic understanding of the triangles and related structures.
PMID- 27510392
TI - Impact of Glycemic Control and Metformin Use on the Recurrence and Progression of
Non-Muscle Invasive Bladder Cancer in Patients with Diabetes Mellitus.
AB - The purpose of the present study was to determine the potential relationships of
glycemic control and use of metformin with non-muscle invasive bladder cancer
characteristics. We reviewed data from 645 patients with non-muscle invasive
bladder cancer between January 2004 and May 2015. We analyzed the association of
pre and post-operative glycemic control and use of metformin with clinical
characteristics of bladder tumors. We also analyzed the association of glycemic
control and use of metformin with recurrence-free and progression-free survivals.
Diabetes mellitus patients showed decreased recurrence-free survival (hazard
ratio 1.42; 95% confidence interval 1.1-1.9; P = 0.021) and progression-free
survival (hazard ratio 1.79; 95% confidence interval 1.1-2.8; P = 0.013).
Diabetes mellitus patients with a HbA1c >= 7.0% demonstrated a higher rate of
progression (P = 0.026). Kaplan-Meier analysis showed that progression-free
survival rate was associated with poor baseline glycemic control (P = 0.026) and
post-operative glycemic control (P = 0.025). However, use of metformin had no
impact on the recurrence (P = 1.00) and progression (P = 0.282). In conclusion,
poor baseline and post-operative glycemic control was related with shorter
progression-free survival of patients with non-muscle invasive bladder cancer.
Use of metformin had no impact on the recurrence and progression. Therefore,
tight glycemic control and close follow-up for bladder tumor may be beneficial in
patients with poor glycemic control.
PMID- 27510393
TI - Ultrasound Dimensions of the Rotator Cuff and Other Associated Structures in
Korean Healthy Adults.
AB - In evaluating patients complaining of shoulder pain, ultrasonography is an
emerging imaging tool due to convenience, low cost, high sensitivity and
specificity. However, normative values of ultrasound dimensions of the shoulder
to be compared with pathologic findings in Korean adults are not provided yet. We
evaluated the ultrasound dimensions of the rotator cuff, long head of biceps
tendon, deltoid muscle and acromioclavicular joint in Korean healthy adults.
Shoulder ultrasonography was performed on 200 shoulders from 100 healthy adults.
The dimensions of the thickness of rotator cuff (supraspinatus, infraspinatus,
subscapularis tendon), deltoid muscle, long head of biceps tendon, subacromial
subdeltoid bursa, and acromioclavicular joint interval were measured in a
standardized manner. Differences in measurements among sex, age, and dominant
arms were compared. The thickness of rotator cuff tendons (supraspinatus,
infraspinatus, subscapularis) and deltoid muscle were significantly different
between men and women. The thickness of subacromial subdeltoid bursa was
significantly different between men and women for non-dominant side. In rotator
cuff tendon measurements, the differences between dominant and non-dominant
shoulders were not significant, which means the asymptomatic contralateral
shoulder can be used to estimate the normal reference values. When stratified by
age divided by 10 years, the measurements of supraspinatus, subscapularis and
deltoid thickness showed tendency of increase with the age. The acromioclavicular
joint interval, on the other hand, revealed decreasing tendency. This report
suggests normative values of ultrasound dimensions of healthy Korean population
with varying age, and can be useful as reference values in evaluating shoulder
pathology, especially in rotator cuff tendon pathology.
PMID- 27510394
TI - High Prevalence of Sarcopenia in Korean Patients after Hip Fracture: a Case
Control Study.
AB - Sarcopenia-related falls and fractures are increasing worldwide due to the aging
population. The purpose of this study was to 1) evaluate anthropometric
characteristics related to hip fracture in Korean patients, 2) investigate
sarcopenia prevalence in hip fracture (HF) and non-hip fracture (NF) groups, and
3) investigate the correlation between sarcopenia and osteoporosis. This case
control study examined 359 HF and 1,614 NF normal populations using Korea
National Health and Nutrition Examination Survey data. We performed whole-body
dual energy X-ray absorptiometry to analyze body composition using the skeletal
muscle mass index (SMI: lean mass/height2) and bone mineral density (BMD). In the
HF group, using the AWGS definition, the prevalence of sarcopenia in women and
men was 44.3% and 68.2%, respectively; in the NF group, it was 7.1% and 16.1%,
respectively. Lower appendicular SMI (P < 0.001), leg muscle mass (P < 0.001),
and higher prevalence of sarcopenia (P < 0.001) were observed in the HF group
after adjustment for age and gender. In multivariate analysis, sarcopenia (OR =
6.52; 95% CI = 4.67-9.09), age (OR = 1.15; 95% CI = 1.13-1.17), and osteoporosis
(OR = 1.87; 95% CI = 1.35-2.58) were associated with the occurrence of a hip
fracture. This study showed a higher prevalence of sarcopenia in patients with
hip fractures compared with a normal population, and higher prevalence of
sarcopenia in men.
PMID- 27510396
TI - A Randomized Controlled Trial of Compression Rates during Cardiopulmonary
Resuscitation.
AB - The objective of this study was to compare the efficacy of cardiopulmonary
resuscitation (CPR) with 120 compressions per minute (CPM) to CPR with 100 CPM in
patients with non-traumatic out-of-hospital cardiac arrest. We randomly assigned
patients with non-traumatic out-of-hospital cardiac arrest into two groups upon
arrival to the emergency department (ED). The patients received manual CPR either
with 100 CPM (CPR-100 group) or 120 CPM (CPR-120 group). The primary outcome
measure was sustained restoration of spontaneous circulation (ROSC). The
secondary outcome measures were survival discharge from the hospital, one-month
survival, and one-month survival with good functional status. Of 470 patients
with cardiac arrest, 136 patients in the CPR-100 group and 156 patients in the
CPR-120 group were included in the final analysis. A total of 69 patients (50.7%)
in the CPR-100 group and 67 patients (42.9%) in the CPR-120 group had ROSC
(absolute difference, 7.8% points; 95% confidence interval [CI], -3.7 to 19.2%; P
= 0.183). The rates of survival discharge from the hospital, one-month survival,
and one-month survival with good functional status were not different between the
two groups (16.9% vs. 12.8%, P = 0.325; 12.5% vs. 6.4%, P = 0.073; 5.9% vs. 2.6%,
P = 0.154, respectively). We did not find differences in the resuscitation
outcomes between those who received CPR with 100 CPM and those with 120 CPM.
However, a large trial is warranted, with adequate power to confirm a
statistically non-significant trend toward superiority of CPR with 100 CPM. (
CLINICAL TRIAL REGISTRATION INFORMATION: www.cris.nih.go.kr, cris.nih.go.kr
number, KCT0000231).
PMID- 27510395
TI - Comparison of an Intraoperative Infusion of Dexmedetomidine, Fentanyl, and
Remifentanil on Perioperative Hemodynamics, Sedation Quality, and Postoperative
Pain Control.
AB - We aimed to compare fentanyl, remifentanil and dexmedetomidine with respect to
hemodynamic stability, postoperative pain control and achievement of sedation at
the postanesthetic care unit (PACU). In this randomized double-blind study, 90
consecutive total laparoscopic hysterectomy patients scheduled for elective
surgery were randomly assigned to receive fentanyl (1.0 MUg/kg) over 1 minute
followed by a 0.4 MUg/kg/hr infusion (FK group, n = 30), or remifentanil (1.0
MUg/kg) over 1 minute followed by a 0.08 MUg/kg/min infusion (RK group, n = 30),
or dexmedetomidine (1 MUg/kg) over 10 minutes followed by a 0.5 MUg/kg/hr
infusion (DK group, n = 30) initiating at the end of main procedures of the
operation to the time in the PACU. A single dose of intravenous ketorolac (30 mg)
was given to all patients at the end of surgery. We respectively evaluated the
pain VAS scores, the modified OAA/S scores, the BIS, the vital signs and the
perioperative side effects to compare the efficacy of fentanyl, remifentanil and
dexmedetomidine. Compared with other groups, the modified OAA/S scores were
significantly lower in DK group at 0, 5 and 10 minutes after arrival at the PACU
(P < 0.05), whereas the pain VAS and BIS were not significantly different from
other groups. The blood pressure and heart rate in the DK group were
significantly lower than those of other groups at the PACU (P < 0.05). DK group,
at sedative doses, had the better postoperative hemodynamic stability than RK
group or FK group and demonstrated a similar effect of pain control as RK group
and FK group with patient awareness during sedation in the PACU. (World Health
Organization registry, KCT0001524).
PMID- 27510397
TI - Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.
AB - Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can
then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South
Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever
persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days
after his return from the journey. Urinalysis showed pyuria and hematuria. Blood
examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular
coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were
performed for 19 hospital days. Falciparum malaria was then confirmed by
peripheral blood smear, and antimalarial medications were initiated. The
patient's condition and laboratory results were quickly normalized. We report a
case of severe acute renal failure associated with delayed diagnosis of
falciparum malaria, and primary use of supportive treatment rather than
antimalarial medicine. The present case suggests that early diagnosis and
treatment is important because untreated tropical malaria can be associated with
severe acute renal failure and fatality. Physicians must be alert for correct
diagnosis and proper management of imported tropical malaria when patients have
travel history of endemic areas.
PMID- 27510398
TI - Letter to the Editor: Objective Assessment of Surgical Restaging after Concurrent
Chemoradiation for Locally Advanced Pancreatic Cancer.
PMID- 27510399
TI - The Author's Response: Objective Assessment of Surgical Restaging after
Concurrent Chemoradiation for Locally Advanced Pancreatic Cancer.
PMID- 27510400
TI - Membranome: a database for proteome-wide analysis of single-pass membrane
proteins.
AB - The Membranome database was developed to assist analysis and computational
modeling of single-pass (bitopic) transmembrane (TM) proteins and their complexes
by providing structural information about these proteins on a genomic scale. The
database currently collects data on >6000 bitopic proteins from Homo sapiens,
Arabidopsis thaliana, Dictyostelium discoideum, Saccharomyces cerevisiae,
Escherichia coli and Methanocaldococcus jannaschii It presents the following
data: (i) hierarchical classification of bitopic proteins into 15 functional
classes, 689 structural superfamilies and 1404 families; (ii) 446 complexes of
bitopic proteins with known three-dimensional (3D) structures classified into 129
families; (iii) computationally generated three-dimensional models of TM alpha
helices positioned in membranes; (iv) amino acid sequences, domain architecture,
functional annotation and available experimental structures of bitopic proteins;
(v) TM topology and intracellular localization, (vi) physical interactions
between proteins from the database along with links to other resources. The
database is freely accessible at http://membranome.org There is a variety of
options for browsing, sorting, searching and retrieval of the content, including
downloadable coordinate files of TM domains with calculated membrane boundaries.
PMID- 27510401
TI - Increased Th2 activity and diminished skin barrier function cooperate in allergic
skin inflammation.
AB - Atopic dermatitis (AD) is a chronic inflammatory skin disease induced by a
complex interaction between susceptibility genes encoding skin barrier components
and environmental allergen exposure that results in type 2 cytokine production.
Although genetic lesions in either component can be risk factors for disease in
patients, whether these pathways interact in the development of AD is not clear.
To test this, we mated mice with T-cell specific expression of constitutively
active Stat6 (Stat6VT) that spontaneously develop allergic skin inflammation with
Flaky tail (Ft) mice that have mutations in Flg and Tmem79 genes that each affect
skin barrier function. Our results demonstrate that over 90% of the Stat6VT
transgenic mice carrying the Ft alleles (Stat6VTxFt-/- ) develop severe atopic
dermatitis lesions by 3-5 months of age, compared with only 40% of Stat6VT mice
that develop disease by 6-7 months of age. Further, histopathological analysis of
skin tissues from Stat6VTxFt-/- mice revealed extensive thickening of the dermis
with increased inflammatory infiltrates as compared with Stat6VT mice. Our study
suggests that skin barrier defects and altered Th2 responses independently
cooperate in the pathogenesis of allergic skin inflammation, similar to effects
observed in patients with AD.
PMID- 27510402
TI - Association of cardiovascular emerging risk factors with acute coronary syndrome
and stroke: A case-control study.
AB - In this study, we estimated the risk of acute coronary syndrome and stroke
associated with several emerging cardiovascular risk factors. This was a case
control study, where an age - and sex-matched acute coronary syndrome group and
stroke group were compared with controls. Demographic and clinical data were
collected through patient interviews, and blood samples were taken for analysis.
In the bivariate analysis, all cardiovascular risk factors analyzed showed as
predictors of acute coronary syndrome and stroke, except total cholesterol and
smoking. In the multivariate logistic regression model for acute coronary
syndrome, hypertension and body mass index, N-terminal section brain natriuretic
peptide and pregnancy-associated plasma protein-A were independent predictors.
For stroke, the predictors were hypertension, diabetes mellitus, body mass index,
and N-terminal section brain natriuretic peptide. Controlling for age, sex, and
classical cardiovascular risk factors, N-terminal section brain natriuretic
peptide and pregnancy-associated plasma protein-A were independent emerging
cardiovascular risk factors for acute coronary syndrome, but pregnancy-associated
plasma protein-A was not for stroke. High levels of cardiovascular risk factors
in individuals with no episodes of cardiovascular disease requires the
implementation of prevention programs, given that at least half of them are
modifiable.
PMID- 27510403
TI - Lanthanide-Catalyzed Reversible Alkynyl Exchange by Carbon-Carbon Single-Bond
Cleavage Assisted by a Secondary Amino Group.
AB - Lanthanide-catalyzed alkynyl exchange through C-C single-bond cleavage assisted
by a secondary amino group is reported. A lanthanide amido complex is proposed as
a key intermediate, which undergoes unprecedented reversible beta-alkynyl
elimination followed by alkynyl exchange and imine reinsertion. The in situ homo-
and cross-dimerization of the liberated alkyne can serve as an additional driving
force to shift the metathesis equilibrium to completion. This reaction is
formally complementary to conventional alkyne metathesis and allows the selective
transformation of internal propargylamines into those bearing different
substituents on the alkyne terminus in moderate to excellent yields under
operationally simple reaction conditions.
PMID- 27510404
TI - Influence of Lumbricus terrestris and Folsomia candida on N2 O formation pathways
in two different soils - with particular focus on N2 emissions.
AB - RATIONALE: The gaseous N losses mediated by soil denitrifiers are generally
inferred by measuring N2 O fluxes, but should include associated N2 emissions,
which may be affected by abiotic soil characteristics and biotic interactions.
Soil fauna, particularly anecic earthworms and euedaphic collembola, alter the
activity of denitrifiers, creating hotspots for denitrification. These soil fauna
are abundant in perennial agroecosystems intended to contribute to more
sustainable production of bioenergy. METHODS: Two microcosm experiments were
designed to evaluate gaseous N emissions from a silty loam and a sandy soil, both
provided with litter from the bioenergy crop Silphium perfoliatum (cup-plant) and
inoculated with an anecic earthworm (Lumbricus terrestris), which was added alone
or together with an euedaphic collembola (Folsomia candida). In experiment 1,
litter-derived N flux was determined by adding 15 N-labelled litter, followed by
mass spectrometric analysis of N2 and N2 O isotopologues. In experiment 2, the
delta18 O values and 15 N site preference of N2 O were determined by isotope
ratio mass spectrometry to reveal underlying N2 O formation pathways. RESULTS:
Lumbricus terrestris significantly increased litter-derived N2 emissions in the
loamy soil, from 174.5 to 1019.3 MUg N2 -N kg-1 soil, but not in the sandy soil
(non-significant change from 944.7 to 1054.7 MUg N2 -N kg-1 soil). Earthworm
feeding on plant litter resulted in elevated N2 O emissions in both soils,
derived mainly from turnover of the soil mineral N pool during denitrification.
Folsomia candida did not affect N losses but showed a tendency to redirect N2 O
formation pathways from fungal to bacterial denitrification. The N2 O/(N2 + N2
O) product ratio was predominantly affected by abiotic soil characteristics
(loamy soil: 0.14, sandy soil: 0.26). CONCLUSIONS: When feeding on S. perfoliatum
litter, the anecic L. terrestris, but not the euedaphic F. candida, has the
potential to cause substantial N losses. Biotic interactions between the species
are not influential, but abiotic soil characteristics have an effect. The coarse
textured sandy soil had lower gaseous N losses attributable to anecic earthworms.
Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27510405
TI - Does state boredom cause failures of attention? Examining the relations between
trait boredom, state boredom, and sustained attention.
AB - Boredom is an important personal and social problem, but the phenomena itself
remains poorly understood. Recent work has shown that boredom is highly related
to attention, and that this relationship may be instrumental in revealing
boredom's causes and consequences. In this paper, experimental findings on trait
boredom, state boredom, and sustained attention performance are presented. We
demonstrate that trait boredom uniquely predicts sustained attention performance,
over and above depression and self-report attention problems. We also present
exploratory findings consistent with the claim that attention failures may cause
boredom and that sustained attention tasks may themselves be boring. Discussion
of each of these findings, and potential ramifications for cognitive research as
a whole, is included.
PMID- 27510406
TI - Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical
Vision Loss in Glaucoma.
AB - Glaucoma is the second leading cause of blindness worldwide and its pathogenesis
remains unclear. In this study, we measured the structure, metabolism and
function of the visual system by optical coherence tomography and multi-modal
magnetic resonance imaging in healthy subjects and glaucoma patients with
different degrees of vision loss. We found that inner retinal layer thinning,
optic nerve cupping and reduced visual cortex activity occurred before patients
showed visual field impairment. The primary visual cortex also exhibited more
severe functional deficits than higher-order visual brain areas in glaucoma.
Within the visual cortex, choline metabolism was perturbed along with increasing
disease severity in the eye, optic radiation and visual field. In summary, this
study showed evidence that glaucoma deterioration is already present in the eye
and the brain before substantial vision loss can be detected clinically using
current testing methods. In addition, cortical cholinergic abnormalities are
involved during trans-neuronal degeneration and can be detected non-invasively in
glaucoma. The current results can be of impact for identifying early glaucoma
mechanisms, detecting and monitoring pathophysiological events and eye-brain
behavior relationships, and guiding vision preservation strategies in the visual
system, which may help reduce the burden of this irreversible but preventable
neurodegenerative disease.
PMID- 27510408
TI - Sphingomyelin synthase 2 affects CD14-associated induction of NF-kappaB by
lipopolysaccharides in acute lung injury in mice.
AB - Lipopolysaccharide (LPS) is the predominant component of the outer membrane of
Gram-negative bacteria, which can cause severe inflammation in the body. The
acute lung injury (ALI) induced by LPS can cause extensive damage to the lung
tissue, the severe stage of which is termed acute respiratory distress syndrome,
when multiple organ dysfunction syndrome may appear. There are no effective
clinical treatment measures at present. The involvement of cluster of
differentiation (CD)14 assists LPS in causing inflammatory reactions, and CD14
and sphingomyelin (SM), located in lipid rafts areas, are closely associated. SM
synthase (SMS) is a key enzyme in the synthesis of SM, however, the effect of SMS
on the inflammatory pathway involving nuclear factor (NF)-kappaB induced by LPS
remains to be elucidated. Under the premise of the establishment of an ALI mouse
model induced by LPS, the present study established a control group, LPS group
and pyrrolidine dithiocarbamate (PDTC; an NF-kappaB pathway inhibitor) group.
Hematoxylin-eosin staining, reverse transcription-quantitative polymerase chain
reaction analysis, western blot analysis and thin layer chromatography were used
to investigate the mechanism of SMS in ALI. Compared with the control group, the
mRNA and protein levels of CD14 were significantly increased (P<0.001; n=5 and
P<0.05, n=5), and the activity of SMS and expression of SMS2 were significantly
upregulated (P<0.001; n=5 and P<0.05, n=5) in the model group. The increases of
SMS2 and CD14 in the PDTC group were less marked, compared with those in the
model group (P<0.05; n=5). These findings suggested that the degree of lung
injury was reduced during the acute inflammatory reaction when NF-kappaB was
inhibited, and that the expression of SMS2 may affect the induction of the NF
kappaB pathway by LPS through CD14.
PMID- 27510407
TI - Impact of language on functional connectivity for audiovisual speech integration.
AB - Visual information about lip and facial movements plays a role in audiovisual
(AV) speech perception. Although this has been widely confirmed, previous
behavioural studies have shown interlanguage differences, that is, native
Japanese speakers do not integrate auditory and visual speech as closely as
native English speakers. To elucidate the neural basis of such interlanguage
differences, 22 native English speakers and 24 native Japanese speakers were
examined in behavioural or functional Magnetic Resonance Imaging (fMRI)
experiments while mono-syllabic speech was presented under AV, auditory-only, or
visual-only conditions for speech identification. Behavioural results indicated
that the English speakers identified visual speech more quickly than the Japanese
speakers, and that the temporal facilitation effect of congruent visual speech
was significant in the English speakers but not in the Japanese speakers. Using
fMRI data, we examined the functional connectivity among brain regions important
for auditory-visual interplay. The results indicated that the English speakers
had significantly stronger connectivity between the visual motion area MT and the
Heschl's gyrus compared with the Japanese speakers, which may subserve lower
level visual influences on speech perception in English speakers in a
multisensory environment. These results suggested that linguistic experience
strongly affects neural connectivity involved in AV speech integration.
PMID- 27510410
TI - Fine Particulate Matter Pollution and Mortality.
PMID- 27510411
TI - Analysis of esophagogastric cancer patients enrolled in the National Cancer
Institute Cancer Therapy Evaluation Program sponsored phase 1 trials.
AB - BACKGROUND: In phase 1 trials, an important entry criterion is life expectancy
predicted to be more than 90 days, which is generally difficult to predict. The
Royal Marsden Hospital (RMH) prognostic score that is determined by lactate
dehydrogenase level, albumin level, and number of metastatic sites of disease was
developed to help project patient outcomes. There have been no systematic
analyses to evaluate the utility of the RMH prognostic score for esophagogastric
cancer patients. METHODS: All nonpediatric phase 1 oncology trials sponsored by
the National Cancer Institute Cancer Therapy Evaluation Program that began
between 2001 and 2013 were considered in this review. RESULTS: Of 4722 patients
with solid tumors, 115 patients were eligible for our analysis; 54 (47 %) with
cancer of the esophagus, 14 (12 %) with cancer of the esopagogastric junction,
and 47 (41 %) with stomach cancer. Eighty-six patients (75 %) had a good RMH
prognostic score (0 or 1) and 29 patients (25 %) had a poor RMH prognostic score
(2 or 3). Disease control rates were significantly different between patients
with good and poor RMH prognostic scores (49 % vs 17 %; two-sided Fisher's exact
test P = 0.004). The median treatment duration and overall survival for good and
poor RMH prognostic score patients were significantly different (median treatment
duration 2.1 months vs 1.2 months respectively, P = 0.016; median overall
survival 10.9 months vs 2.1 months respectively, P < 0.001). In the multivariate
analysis, age (60 years or older), Eastern Cooperative Oncology Group performance
status (2 or greater), and the RMH prognostic score (2 or 3) were significant
predictors of poor survival. CONCLUSIONS: The RMH prognostic score is a strong
tool to predict the prognosis of esophagogastric cancer patients who might
participate in a phase 1 trial.
PMID- 27510413
TI - Acceleration of convective dissolution by chemical reaction in a Hele-Shaw cell.
AB - New laboratory experiments quantify the destabilising effect of a second-order
chemical reaction on the fingering instability of a diffusive boundary layer in a
Hele-Shaw cell. We show that, for a given chemical system, the dynamics of such a
reactive boundary layer is fully determined by two dimensionless groups,
Da/Ra(2), which measures the timescale for convection compared to those for
reaction and diffusion, and CBo', which reflects the excess of the environmental
reactant species relative to the diffusing solute. Results of a systematic study
varying CBo' in the range 0-0.1 are presented. It is shown that the chemical
reaction increases the growth rate of a perturbation and favours small
wavelengths compared to the inert system. A higher concentration of CBo' not only
accelerates the onset of convection, but crucially also increases the transport
of the solute by up to 150% compared to the inert system. This increase in solute
transfer has important practical implications, such as in the storage of carbon
dioxide in saline aquifers.
PMID- 27510412
TI - How Reliable Is the Pinaya Method for Assessing Cognitive Lateralization with
Functional Transcranial Doppler Ultrasound?
PMID- 27510414
TI - Impact of hepatitis B on mortality and specific causes of death in adults with
and without HIV co-infection in NYC, 2000-2011.
AB - High rates of immigration from endemic countries contribute to the high chronic
hepatitis B (HBV) prevalence in New York City (NYC) compared to the United States
overall, i.e. about 1 million individuals. We describe the impact of HBV
infection on mortality and specific causes of death in NYC. We matched
surveillance and vital statistics mortality data collected from 2000 to 2011 by
the New York City Department of Health and Mental Hygiene (DOHMH) and analysed
demographics and premature deaths (i.e. whether death occurred at <65 years) in
persons with and without chronic HBV or HIV infection (excluding those with
hepatitis C). From 2000 to 2011, a total of 588 346 adults died in NYC. Of all
decedents, 568 753 (97%) had no report of HIV or HBV, and 4346 (0.7%) had an HBV
report. Of HBV-infected decedents, 1074 (25%) were HIV co-infected. Fifty-five
percent of HBV mono-infected and 95% of HBV/HIV co-infected decedents died
prematurely. HBV disproportionately impacts two subgroups: Chinese immigrants and
HIV-infected individuals. These two subgroups are geographically clustered in
different neighbourhoods of NYC. Tailoring prevention and treatment messages to
each group is necessary to reduce the overall burden of HBV in NYC.
PMID- 27510415
TI - The trophoblast plug during early pregnancy: a deeper insight.
AB - During the first trimester of pregnancy, foetal endovascular trophoblasts invade
into maternal spiral arteries, accumulate and form plugs in the lumen of the
vessels. These plugs only allow blood plasma to seep through. Hence, during the
first trimester of pregnancy, a first flow of fluids through the placental
intervillous space is established, resulting in a physiological oxygen gradient
between mother and foetus. The trophoblast plugs block spiral arteries until the
beginning of the second trimester (11-14 weeks). In parallel, uterine glands are
invaded and opened by endoglandular trophoblasts towards the intervillous space
of the placenta, without showing the formation of plugs (Moser et al. in Hum
Reprod 25:1127-1136, 2010, Hum Reprod Oxf Engl 30:2747-2757, 2015). This enables
histiotrophic nutrition of the embryo prior to onset of maternal blood flow into
the placenta. Failure of these endovascular and endoglandular invasion processes
may lead to miscarriage or pregnancy disorders such as intrauterine growth
restriction (IUGR). After dissolution of the plugs, the onset of maternal blood
flow allows maternal blood cells to enter the intervillous space and oxygen
concentrations rise up. In this study, we demonstrate for the first time serial
cross sections through a trophoblast plug in a first trimester placental bed
specimen. Invaded and plugged arteries as well as invaded uterine glands in week
11 of gestation are visualized with specific immunohistochemical double staining
techniques. We show that spiral artery plugs appear throughout the placental
invasion zone and illustrate erythrocytes stowed due to trophoblast plugs. In
addition, we give evidence of the presence of MMP-1 in plugs of invaded spiral
arteries. The results reveal a better understanding and a closer insight into the
morphological appearance of trophoblast plugs and the consequences for placental
and uterine blood flow.
PMID- 27510416
TI - In Focus in HCB.
PMID- 27510417
TI - [Predictive PD-L1 immunohistochemistry for non-small cell lung cancer : Current
state of the art and experiences of the first German harmonization study].
AB - BACKGROUND: Antibodies against PD-1 and PD-L1 can cause strong and durable anti
tumor immune responses in non-small cell lung cancer (NSCLC).
Immunohistochemistry for PD-L1 (PD-L1 IHC) was tested as a predictive biomarker.
Several IHC assays and interpretation criteria were developed in parallel. AIM:
The clinical significance of PD-L1 IHC in NSCLC and the optimum method for
staining and interpretation of the results are the subject of ongoing studies.
The diagnostic application of immunotherapy in NSCLC necessitates harmonization
of PD-L1 IHC to obtain evidence for guidelines; therefore, a consensus opinion on
a well-founded diagnostic mode of testing should be defined based on published
studies and the results of the first German PD-L1 IHC harmonization study.
METHODS: 1. Summary of the current data situation. 2. Evaluation of the first
German PD-L1 IHC harmonization study (centralized, staining with PD-L1 IHC
analogous to studies, 15 cases of NSCLC, 4 IHC study assays [28-8, 22C3, SP142
and SP263] and scoring by 9 pathologists). RESULTS: The use of PD-L1 IHC in NSCLC
is suitable for identification of patients with an increased probability of a
clinical benefit from immunotherapy. The various proportional cut-offs used to
interpret the staining results can be summarized in a total score, which can be
reproducibly assessed. The staining patterns of the four assays investigated
were, however, not congruent in all situations. DISCUSSION: In principle, the use
of PD-L1 IHC for assessment of the expression in tumor cells is a reliably
determinable biomarker. Evaluation algorithms should be based on published
clinical trials. For NSCLC approvals with obligatory PD-L1 IHC are to be expected
but it remains to be seen to what extent PD-L1 IHC will be implemented in the
clinical routine.
PMID- 27510418
TI - Room-temperature ferroelectricity in CuInP2S6 ultrathin flakes.
AB - Two-dimensional (2D) materials have emerged as promising candidates for various
optoelectronic applications based on their diverse electronic properties, ranging
from insulating to superconducting. However, cooperative phenomena such as
ferroelectricity in the 2D limit have not been well explored. Here, we report
room-temperature ferroelectricity in 2D CuInP2S6 (CIPS) with a transition
temperature of ~320 K. Switchable polarization is observed in thin CIPS of ~4 nm.
To demonstrate the potential of this 2D ferroelectric material, we prepare a van
der Waals (vdW) ferroelectric diode formed by CIPS/Si heterostructure, which
shows good memory behaviour with on/off ratio of ~100. The addition of
ferroelectricity to the 2D family opens up possibilities for numerous novel
applications, including sensors, actuators, non-volatile memory devices, and
various vdW heterostructures based on 2D ferroelectricity.
PMID- 27510419
TI - Quantitative analysis of mucosal oxygenation using ex vivo imaging of healthy and
inflamed mammalian colon tissue.
AB - Colonic inflammation is associated with decreased tissue oxygenation,
significantly affecting gut homeostasis. However, the crosstalk between O2
consumption and supply in the inflamed tissue are not fully understood. Using a
murine model of colitis, we analysed O2 in freshly prepared samples of healthy
and inflamed colon tissue. We developed protocols for efficient ex vivo staining
of mouse distal colon mucosa with a cell-penetrating O2 sensitive probe Pt-Glc
and high-resolution imaging of O2 concentration in live tissue by confocal
phosphorescence lifetime-imaging microscopy (PLIM). Microscopy analysis revealed
that Pt-Glc stained mostly the top 50-60 MUm layer of the mucosa, with high
phosphorescence intensity in epithelial cells. Measured O2 values in normal mouse
tissue ranged between 5 and 35 MUM (4-28 Torr), tending to decrease in the deeper
tissue areas. Four-day treatment with dextran sulphate sodium (DSS) triggered
colon inflammation, as evidenced by an increase in local IL6 and mKC mRNA levels,
but did not affect the gross architecture of colonic epithelium. We further
observed an increase in oxygenation, partial activation of hypoxia inducible
factor (HIF) 1 signalling, and negative trends in pyruvate dehydrogenase activity
and O2 consumption rate in the colitis mucosa, suggesting a decrease in
mitochondrial respiration, which is known to be regulated via HIF-1 signalling
and pyruvate oxidation rate. These results along with efficient staining with Pt
Glc of rat and human colonic mucosa reveal high potential of PLIM platform as a
powerful tool for the high-resolution analysis of the intestinal tissue
oxygenation in patients with inflammatory bowel disease and other pathologies,
affecting tissue respiration.
PMID- 27510420
TI - Liver X receptors: from cholesterol regulation to neuroprotection-a new barrier
against neurodegeneration in amyotrophic lateral sclerosis?
AB - Cholesterol plays a central role in numerous nervous system functions.
Cholesterol is the major constituent of myelin sheaths, is essential for synapse
and dendrite formation, axon guidance as well as neurotransmission. Among
regulators of cholesterol homeostasis, liver X receptors (LXRs), two members of
the nuclear receptor superfamily, play a determinant role. LXRs act as
cholesterol sensors and respond to high intracellular cholesterol concentration
by decreasing plasmatic and intracellular cholesterol content. Beyond their
cholesterol-lowering role, LXRs have been proposed as regulators of immunity and
anti-inflammatory factors. Dysregulation of cholesterol metabolism combined to
neuroinflammatory context have been described in neurodegenerative diseases,
including amyotrophic lateral sclerosis (ALS). ALS is characterized by the
progressive loss of motoneurons in the brain and spinal cord, leading to severe
paralytic condition and death of patients in a median time of 3 years. Motoneuron
degeneration is accompanied by chronic neuroinflammatory response, involving
microglial and astrocytic activation, infiltration of blood-derived immune cells
and release of pro-inflammatory factors. We propose to discuss here the role of
LXRs as a molecular link between the central nervous system cholesterol
metabolism, neuroinflammation, motoneuron survival and their potential as
promising therapeutic candidates for ALS therapy.
PMID- 27510421
TI - Intracellular localization of DR5 and related regulatory pathways as a mechanism
of resistance to TRAIL in cancer.
AB - TNF-related apoptosis-inducing ligand (TRAIL) is a prominent cytokine capable of
inducing apoptosis. It can bind to five different cognate receptors, through
which diverse intracellular pathways can be activated. TRAIL's ability to
preferentially kill transformed cells makes it a promising potential weapon for
targeted tumor therapy. However, recognition of several resistance mechanisms to
TRAIL-induced apoptosis has indicated that a thorough understanding of the
details of TRAIL biology is still essential before this weapon can be confidently
unleashed. Critical to this aim is revealing the functions and regulation
mechanisms of TRAIL's potent death receptor DR5. Although expression and
signaling mechanisms of DR5 have been extensively studied, other aspects, such as
its subcellular localization, non-signaling functions, and regulation of its
membrane transport, have only recently attracted attention. Here, we discuss
different aspects of TRAIL/DR5 biology, with a particular emphasis on the factors
that seem to influence the cell surface expression pattern of DR5, along with
factors that lead to its nuclear localization. Disturbance of this balance
apparently affects the sensitivity of cancer cells to TRAIL-mediated apoptosis,
thus constituting an eligible target for potential new therapeutic agents.
PMID- 27510422
TI - Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity.
AB - Sleep disturbances including insomnia independently contribute to risk of
inflammatory disorders and major depressive disorder. This review and overview
provides an integrated understanding of the reciprocal relationships between
sleep and the innate immune system and considers the role of sleep in the
nocturnal regulation of the inflammatory biology dynamics; the impact of insomnia
complaints, extremes of sleep duration, and experimental sleep deprivation on
genomic, cellular, and systemic markers of inflammation; and the influence of
sleep complaints and insomnia on inflammaging and molecular processes of cellular
aging. Clinical implications of this research include discussion of the
contribution of sleep disturbance to depression and especially inflammation
related depressive symptoms. Reciprocal action of inflammatory mediators on the
homeostatic regulation of sleep continuity and sleep macrostructure, and the
potential of interventions that target insomnia to reverse inflammation, are also
reviewed. Together, interactions between sleep and inflammatory biology
mechanisms underscore the implications of sleep disturbance for inflammatory
disease risk, and provide a map to guide the development of treatments that
modulate inflammation, improve sleep, and promote sleep health.
PMID- 27510424
TI - Thinking Outside the Box: Orbitofrontal Cortex, Imagination, and How We Can Treat
Addiction.
AB - Addiction involves an inability to control drug-seeking behavior. While this may
be thought of as secondary to an overwhelming desire for drugs, it could equally
well reflect a failure of the brain mechanisms that allow addicts to learn about
and mentally simulate non-drug consequences. Importantly, this process of mental
simulation draws upon, but is not normally bound by, our past experiences. Rather
we have the ability to think outside the box of our past, integrating knowledge
gained from a variety of similar and not-so-similar life experiences to derive
estimates or imagine what might happen next. These estimates influence our
current behavior directly and also affect future behavior by serving as the
background against which outcomes are evaluated to support learning. Here we will
review evidence, from our own work using a Pavlovian over-expectation task as
well as from other sources, that the orbitofrontal cortex is a critical node in
the neural circuit that generates these estimates. Further we will offer the
specific hypothesis that degradation of this function secondary to drug-induced
changes is a critical and likely addressable part of addiction.
PMID- 27510425
TI - Low MU-Opioid Receptor Status in Alcohol Dependence Identified by Combined
Positron Emission Tomography and Post-Mortem Brain Analysis.
AB - Blockade of the MU-opioid receptor (MOR) by naltrexone reduces relapse risk in a
subpopulation of alcohol-dependent patients. Previous positron-emission
tomography (PET) studies using the MOR ligand [11C]carfentanil have found
increased MOR availability in abstinent alcoholics, which may reflect either
increased MOR expression or lower endogenous ligand concentration. To
differentiate between both effects, we investigated two cohorts of alcoholic
subjects using either post-mortem or clinical PET analysis. Post-mortem brain
tissue of alcohol-dependent subjects and controls (N=43/group) was quantitatively
analyzed for MOR ([3H]DAMGO)-binding sites and OPRM1 mRNA in striatal regions.
[11C]carfentanil PET was performed in detoxified, medication free alcohol
dependent patients (N=38), followed by a randomized controlled study of
naltrexone versus placebo and follow-up for 1 year (clinical trial number:
NCT00317031). Because the functional OPRM1 variant rs1799971:A>G affects the
ligand binding, allele carrier status was considered in the analyses. MOR-binding
sites were reduced by 23-51% in post-mortem striatal tissue of alcoholics. In the
PET study, a significant interaction of OPRM1 genotype, binding potential (BPND)
for [11C]carfentanil in the ventral striatum, and relapse risk was found.
Particularly in G-allele carriers, lower striatal BPND was associated with a
higher relapse risk. Interestingly, this effect was more pronounced in the
naltrexone treatment group. Reduced MOR is interpreted as a neuroadaptation to an
alcohol-induced release of endogenous ligands in patients with severe alcoholism.
Low MOR availability may explain the ineffectiveness of naltrexone treatment in
this subpopulation. Finally, low MOR-binding sites are proposed as a molecular
marker for a negative disease course.
PMID- 27510427
TI - Insignificance of active flow for neural diffusion weighted imaging: A negative
result.
AB - PURPOSE: To provide a biophysical basis to estimate the effect of cytoplasmic
flow in neurons, and assess their contribution to the drop in the Apparent
Diffusion Coefficient (ADC) in a nerve tissue following extreme conditions, such
as brain injury and epileptic seizures. METHODS: Three mechanisms are treated
using the relevant physics of hydrodynamics and electrostatics: cargo induced
streaming, electroosmosis, and membrane swelling. RESULTS: We begin by discussing
the lack of experimental evidence on the necessary velocities required to
influence the Magnetic Resonance (MR) experiments. This is followed by
demonstrating that cargo induced streaming, a widely known phenomenon in plant
cells, has a minor effect on the ADC in neurons. Subsequently, we suggest and
analyze two additional mechanisms that may induce fluid displacement in neurons,
and are related to the electrical activity: electroosmosis and membrane swelling.
CONCLUSION: Although these mechanisms may induce interesting fluid displacements,
these cannot explain the significant drop in the ADC. We conclude by outlining
the criteria that any future mechanism should meet to have an influence on
standard diffusion-MR measurements. Magn Reson Med 78:746-753, 2017. (c) 2016
International Society for Magnetic Resonance in Medicine.
PMID- 27510423
TI - Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond.
AB - The study of inflammation in fear- and anxiety-based disorders has gained
interest as growing literature indicates that pro-inflammatory markers can
directly modulate affective behavior. Indeed, heightened concentrations of
inflammatory signals, including cytokines and C-reactive protein, have been
described in posttraumatic stress disorder (PTSD), generalized anxiety disorder
(GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.).
However, not all reports indicate a positive association between inflammation and
fear- and anxiety-based symptoms, suggesting that other factors are important in
future assessments of inflammation's role in the maintenance of these disorders
(ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources
of inflammation). The most parsimonious explanation of increased inflammation in
PTSD, GAD, PD, and phobias is via the activation of the stress response and
central and peripheral immune cells to release cytokines. Dysregulation of the
stress axis in the face of increased sympathetic tone and decreased
parasympathetic activity characteristic of anxiety disorders could further
augment inflammation and contribute to increased symptoms by having direct
effects on brain regions critical for the regulation of fear and anxiety (such as
the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the
available data suggest that targeting inflammation may serve as a potential
therapeutic target for treating these fear- and anxiety-based disorders in the
future. However, the field must continue to characterize the specific role pro
inflammatory signaling in the maintenance of these unique psychiatric conditions.
PMID- 27510428
TI - Acid and alkaline phosphatase localization in the digestive tract mucosa of the
Hemisorubim platyrhynchos.
AB - This cytochemical study investigated the acid and alkaline phosphatase of the
digestive tract of Hemisorubim platyrhynchos. Acid phosphatase was detected in
the lining epithelium throughout the digestive tract, whereas alkaline
phosphatase was only observed in the intestine. In the esophagus, an acid
phosphatase reaction occurred in the apical cytoplasm of the epithelial cells and
was related to epithelial protection and freeing of superficial cells for
sloughing. Similar results were also observed in epithelial cells of gastric
epithelium. In the gastric glands, acid phosphatase occurred in lysosomes of the
oxynticopeptic cells acting in the macromolecule degradation for use as an energy
source, whereas in the vesiculotubular system, its presence could be related to
secretion processes. Furthermore, acid phosphatase in the intestine occurred in
microvilli and lysosomes of the enterocytes and was correlated to absorption and
intracellular digestion. However, no difference was reported among the regions of
the intestine. However, alkaline phosphatase reaction revealed a large number of
reaction dots in the anterior intestine, with the number decreasing toward the
posterior intestine. This enzyme has been related to several functions,
highlighting its role in the nutrient absorption primarily in the anterior
intestine but also being essential in pH regulation because this is a carnivorous
species with many gastric glands with secretions that could damage the intestine.
PMID- 27510426
TI - Genetic Studies on the Tripartite Glutamate Synapse in the Pathophysiology and
Therapeutics of Mood Disorders.
AB - Both bipolar disorder (BD) and major depressive disorder (MDD) have high
morbidity and share a genetic background. Treatment options for these mood
disorders are currently suboptimal for many patients; however, specific genetic
variables may be involved in both pathophysiology and response to treatment.
Agents such as the glutamatergic modulator ketamine are effective in treatment
resistant mood disorders, underscoring the potential importance of the
glutamatergic system as a target for improved therapeutics. Here we review
genetic studies linking the glutamatergic system to the pathophysiology and
therapeutics of mood disorders. We screened 763 original genetic studies of BD or
MDD that investigated genes encoding targets of the pathway/mediators related to
the so-called tripartite glutamate synapse, including pre- and post-synaptic
neurons and glial cells; 60 papers were included in this review. The findings
suggest the involvement of glutamate-related genes in risk for mood disorders,
treatment response, and phenotypic characteristics, although there was no
consistent evidence for a specific gene. Target genes of high interest included
GRIA3 and GRIK2 (which likely play a role in emergent suicidal ideation after
antidepressant treatment), GRIK4 (which may influence treatment response), and
GRM7 (which potentially affects risk for mood disorders). There was stronger
evidence that glutamate-related genes influence risk for BD compared with MDD.
Taken together, the studies show a preliminary relationship between glutamate
related genes and risk for mood disorders, suicide, and treatment response,
particularly with regard to targets on metabotropic and ionotropic receptors.
PMID- 27510429
TI - Changes of trehalose content and expression of relative genes during the
bioethanol fermentation by Saccharomyces cerevisiae.
AB - Traditionally, trehalose is considered as a protectant to improve the ethanol
tolerance of Saccharomyces cerevisiae. In this study, to clarify the changes and
roles of trehalose during the bioethanol fermentation, trehalose content and
expression of related genes at lag, exponential, and stationary phases (i.e., 2,
8, and 16 h of batch fermentation process) were determined. Although yeast cells
at exponential and stationary phase had higher trehalose content than cells at
lag phase (P < 0.01), there was no significant difference in trehalose content
between exponential and stationary phases (P > 0.05). Moreover, expression of the
trehalose degradation-related genes NTH1 and NTH2 decreased at exponential phase
in comparison with that at lag phase; compared with cells at lag phase, cells at
stationary phase had higher expression of TPS1, ATH1, NTH1, and NTH2 but lower
expression of TPS2. During the lag-exponential phase transition, downregulation
of NTH1 and NTH2 promoted accumulation of trehalose, and to some extent,
trehalose might confer ethanol tolerance to S. cerevisiae before stationary
phase. During the exponential-stationary phase transition, upregulation of TPS1
contributed to accumulation of trehalose, and Tps1 protein might be indispensable
in yeast cells to withstand ethanol stress at the stationary phase. Moreover,
trehalose would be degraded to supply carbon source at stationary phase.
PMID- 27510431
TI - Predicting Pt-195 NMR chemical shift using new relativistic all-electron basis
set.
AB - Predicting NMR properties is a valuable tool to assist the experimentalists in
the characterization of molecular structure. For heavy metals, such as Pt-195,
only a few computational protocols are available. In the present contribution,
all-electron Gaussian basis sets, suitable to calculate the Pt-195 NMR chemical
shift, are presented for Pt and all elements commonly found as Pt-ligands. The
new basis sets identified as NMR-DKH were partially contracted as a triple-zeta
doubly polarized scheme with all coefficients obtained from a Douglas-Kroll-Hess
(DKH) second-order scalar relativistic calculation. The Pt-195 chemical shift was
predicted through empirical models fitted to reproduce experimental data for a
set of 183 Pt(II) complexes which NMR sign ranges from -1000 to -6000 ppm.
Furthermore, the models were validated using a new set of 75 Pt(II) complexes,
not included in the descriptive set. The models were constructed using non
relativistic Hamiltonian at density functional theory (DFT-PBEPBE) level with NMR
DKH basis set for all atoms. For the best model, the mean absolute deviation
(MAD) and the mean relative deviation (MRD) were 150 ppm and 6%, respectively,
for the validation set (75 Pt-complexes) and 168 ppm (MAD) and 5% (MRD) for all
258 Pt(II) complexes. These results were comparable with relativistic DFT
calculation, 200 ppm (MAD) and 6% (MRD). (c) 2016 Wiley Periodicals, Inc.
PMID- 27510432
TI - A red emitting two-photon fluorescent probe for dynamic imaging of redox balance
meditated by a superoxide anion and GSH in living cells and tissues.
AB - Cellular self-regulation of reactive oxygen species (ROS) stress via antioxidant
repair plays an important role in maintaining the redox balance. The redox
balance between reducing and oxidizing species within cells is significant in the
regulation of a signal pathway and is achieved by a series of elaborate
mechanisms. In this work, we employed our previously reported D-pi-A-structured
naphthalene-BODIPY TBET platform to design an efficient two-photon fluorescent
probe for dynamic monitoring of superoxide anion oxidative stress and the GSH
reducing repair process. The probe displayed high energy transfer efficiency
(91.4%), large pseudo-Stokes shifts upon one-photon excitation, and red
fluorescence emission (lambdaem = 596 nm), which is highly desirable for
bioimaging applications. The probe exhibits reversibility, rapid response, good
photostability, high selectivity and sensitivity for the superoxide anion and
GSH. More importantly, the probe was successfully applied for visualizing the
redox changes in living cells and tissues.
PMID- 27510430
TI - TRPV4 regulates calcium homeostasis, cytoskeletal remodeling, conventional
outflow and intraocular pressure in the mammalian eye.
AB - An intractable challenge in glaucoma treatment has been to identify druggable
targets within the conventional aqueous humor outflow pathway, which is thought
to be regulated/dysregulated by elusive mechanosensitive protein(s). Here,
biochemical and functional analyses localized the putative mechanosensitive
cation channel TRPV4 to the plasma membrane of primary and immortalized human TM
(hTM) cells, and to human and mouse TM tissue. Selective TRPV4 agonists and
substrate stretch evoked TRPV4-dependent cation/Ca(2+) influx, thickening of F
actin stress fibers and reinforcement of focal adhesion contacts. TRPV4
inhibition enhanced the outflow facility and lowered perfusate pressure in
biomimetic TM scaffolds populated with primary hTM cells. Systemic delivery,
intraocular injection or topical application of putative TRPV4 antagonist prodrug
analogs lowered IOP in glaucomatous mouse eyes and protected retinal neurons from
IOP-induced death. Together, these findings indicate that TRPV4 channels function
as a critical component of mechanosensitive, Ca(2+)-signaling machinery within
the TM, and that TRPV4-dependent cytoskeletal remodeling regulates TM stiffness
and outflow. Thus, TRPV4 is a potential IOP sensor within the conventional
outflow pathway and a novel target for treating ocular hypertension.
PMID- 27510434
TI - Super non-linear RRAM with ultra-low power for 3D vertical nano-crossbar arrays.
AB - Vertical crossbar arrays provide a cost-effective approach for high density three
dimensional (3D) integration of resistive random access memory. However, an
individual selector device is not allowed to be integrated with the memory cell
separately. The development of V-RRAM has impeded the lack of satisfactory self
selective cells. In this study, we have developed a high performance bilayer self
selective device using HfO2 as the memory switching layer and a mixed ionic and
electron conductor as the selective layer. The device exhibits high non-linearity
(>10(3)) and ultra-low half-select leakage (<0.1 pA). A four layer vertical
crossbar array was successfully demonstrated based on the developed self
selective device. High uniformity, ultra-low leakage, sub-nA operation, self
compliance, and excellent read/write disturbance immunity were achieved. The
robust array level performance shows attractive potential for low power and high
density 3D data storage applications.
PMID- 27510433
TI - Risk factors for severe clinical events in male and female patients with Fabry
disease treated with agalsidase beta enzyme replacement therapy: Data from the
Fabry Registry.
AB - BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, causes
intracellular accumulation of glycosphingolipids leading to progressive renal,
cardiovascular, and cerebrovascular disease, and premature death. METHODS: This
longitudinal Fabry Registry study analyzed data from patients with Fabry disease
to determine the incidence and type of severe clinical events following
initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as
risk factors associated with occurrence of these events. Severe events assessed
included chronic dialysis, renal transplantation, cardiac events, stroke, and
death. RESULTS: The analyses included 969 male and 442 female Fabry patients. The
mean age at first agalsidase beta infusion was 35 and 44, and median treatment
follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were
the most common on-ERT events, followed by renal, stroke, and non-cardiac death.
Among females, cardiac events were also most common followed by stroke and renal
events. Patients with on-ERT events had significantly more advanced cardiac and
renal disease at baseline as compared with patients without on-ERT events. Severe
events were also associated with older age at ERT initiation (males and females),
a history of pre-ERT events (females; approaching statistical significance in
males), and a higher urinary protein/creatinine ratio (females). Approximately
65% of patients with pre-ERT events did not experience subsequent on-ERT events.
Of patients without pre-ERT events, most (84% of males, 92% of females) remained
event-free. CONCLUSIONS: Patients with on-ERT severe events had more advanced
Fabry organ involvement at baseline than those without such events and patients
who initiated ERT at a younger age had less residual risk of on-ERT events. The
observed patterns of residual risk may aid clinicians in multidisciplinary
monitoring of male and female patients with Fabry disease receiving ERT, and in
determining the need for administration of adjunctive therapies.
PMID- 27510435
TI - Direct-write liquid phase transformations with a scanning transmission electron
microscope.
AB - The highly energetic electron beam (e-beam) in a scanning transmission electron
microscope (STEM) can induce local changes in the state of matter, ranging from
knock-on and atomic movement, to amorphization/crystallization, and to localized
chemical/electrochemical reactions. To date, fundamental studies of e-beam
induced phenomena and practical applications have been limited by conventional
STEM e-beam rastering modes that allow only for uniform e-beam exposures. Here,
an automated liquid phase nanolithography method has been developed that enables
the direct writing of nanometer scaled features within microfabricated liquid
cells. An external e-beam control system, connected to the scan coils of an
aberration-corrected STEM, is used to precisely control the position, dwell time,
and scan rate of a sub-nanometer STEM probe. Site-specific locations in a sealed
liquid cell containing an aqueous solution of H2PdCl4 are irradiated to deposit
palladium nanocrystals onto silicon nitride membranes in a highly controlled
manner. The threshold electron dose required for the radiolytic deposition of
metallic palladium has been determined, the influence of electron dose on the
nanolithographically patterned feature size and morphology is explored, and a
feedback-controlled monitoring method for active control of the nanofabricated
structures through STEM detector signal monitoring is proposed. This approach
enables fundamental studies of electron beam induced interactions with matter in
liquid cells and opens new pathways to fabricate nanostructures with tailored
architectures and chemistries via shape-controlled nanolithographic patterning
from liquid-phase precursors.
PMID- 27510436
TI - Ionic Liquid Induced Band Shift of Titanium Dioxide.
AB - Ionic liquids (ILs) have become an established option for the use as electrolytes
in dye-sensitized solar cells. In the present study, the adsorption of a
multitude of different ILs on a TiO2 surface is studied systematically, focusing
on the energetic modifications of the semiconductor. The cation was found to
generally cause an energetic downward shift of the TiO2 band levels by accepting
electron density from the surface, and the anions were observed to function in
the opposite direction, raising the energy levels by donating electron density.
Both effects counterbalance each other, leaving the desired outcome dependent on
the choice of the specific IL, i.e., the choice of the cation/anion combination.
The correlation of the band levels with the properties of the IL was successfully
achieved. The dipole moment of the adsorbed ionic liquid species showed little to
no correlation with the semiconductor energetics, but the charge transfer
calculated by radical Voronoi tessellation revealed a high correlation. The
current findings contribute to a deeper understanding of the role of the
electrolyte in dye-sensitized solar cells, and ILs in general, and help with
choosing and tuning of the electrolyte solutions in existing applications.
PMID- 27510437
TI - Melatonin prevents radiation-induced oxidative stress and periodontal tissue
breakdown in irradiated rats with experimental periodontitis.
AB - BACKGROUND AND OBJECTIVE: The aim of this study was to analyze the biochemical
and histochemical effects of radiation therapy and protective melatonin
administration on periodontal tissues in rats with experimental periodontitis.
MATERIAL AND METHODS: Sixty male Sprague Dawley rats were divided into six
groups, as follows: control; experimental periodontitis (Ped); radiotherapy
administration (Rt); experimental periodontitis and exposure to irradiation (Ped
Rt); radiotherapy and protective melatonin administration (Rt-Mel); and
periodontitis, radiation therapy and protective melatonin administration (Ped-Rt
Mel). The rats were killed at the end of the experimental procedure, and the
oxidative stress level and periodontal destruction were compared among the
groups. RESULTS: The oxidative stress index and the levels of 8-hydroxy-2'
deoxyguanosine, malondialdehyde and C-terminal telopeptide of type I collagen
were found to be significantly higher in the Ped-Rt group compared with the Ped
group (p < 0.05), and the levels were lower in the Ped-Rt-Mel group than in the
Ped-Rt group (p < 0.05). Alveolar bone destruction and attachment level were also
significantly lower in the Ped-Rt-Mel group than in the Ped-Rt group (p < 0.05).
CONCLUSION: It was found that radiotherapy increased oxidative stress, the
periodontal attachment level and alveolar bone loss, and protective melatonin
administration significantly reduced the oxidative parameters and prevented
periodontal damage in irradiated rats with experimental periodontitis. Further
research is needed regarding the use of systemic melatonin administration before
radiation therapy.
PMID- 27510438
TI - Biatrial thrombi resembling myxoma regressed after prolonged anticoagulation in a
patient with mitral stenosis: a case report.
AB - BACKGROUND: Many cases of cardiac masses have been reported in the literature,
but in this case report we described a rare case of biatrial cardiac mass that
represented a challenge for diagnosis and therapy. The differentiation between
cardiac masses such as thrombi, vegetations, myxomas and other tumors is not
always straightforward and an exact diagnosis is important because of its
distinct treatment strategy. Transthoracic/esophageal echocardiography and
cardiac magnetic resonance play an important role in establishing the diagnosis
of cardiac masses. However, no current noninvasive diagnostic tool has the
ability to absolutely diagnose cardiac masses; obtaining a pathological specimen
by surgical resection of cardiac masses is the only reliable method to diagnose
cardiac masses accurately. Our case report is an exception in that the final
diagnosis was affirmed by empirical anticoagulation therapy based on clinical
judgment and noninvasive characterization of biatrial mass. CASE PRESENTATION: We
described a 54-year-old Malay man with severe mitral stenosis and atrial
fibrillation who presented with a biatrial mass. Transthoracic/esophageal
echocardiography and cardiac magnetic resonance detected a large, homogeneous
right atrial mass typical of a thrombus, and a left atrial mass adhering to
interatrial septum that mimicked atrial myxoma. The risk factors, morphology,
location, and characteristics of the biatrial cardiac mass indicated a diagnosis
of thrombi. However, our patient declined surgery. As a result, the nature of his
cardiac masses was not specified by histology. Of note, his left atrial mass was
completely regressed by long-term warfarin, leaving a residual right atrial mass.
Thus, we affirmed the most probable diagnosis of cardiac thrombi. During the
course of treatment, he had an episode of non-fatal ischemic stroke most probably
because of a thromboembolism. CONCLUSIONS: Noninvasive characterization of
cardiac mass is essential in clarifying the diagnosis and directing treatment
strategy. Anticoagulation is a feasible treatment when the clinical assessment,
risk factors, and imaging findings indicate a diagnosis of thrombi. After
prolonged anticoagulation therapy, complete resolution of biatrial thrombi was
achievable in our case.
PMID- 27510439
TI - Temper Loss and Persistent Irritability in Preschoolers: Implications for
Diagnosing Disruptive Mood Dysregulation Disorder in Early Childhood.
AB - Disruptive Mood Dysregulation Disorder (DMDD) is a new and controversial child
psychiatric disorder characterized by persistent irritability and frequent temper
loss. Among the controversies surrounding DMDD is whether the age of onset
criterion-that DMDD may not be diagnosed before age 6 years-is justified. This
study examined DMDD symptoms and associated patterns of psychiatric comorbidity,
behavioral, and family functioning in a sample of 139 preschoolers (ages 4-0 to 5
11 years) admitted to an early childhood psychiatric day treatment program. DMDD
symptoms were common in this acute clinical sample, with 63 children (45.3 %)
presenting with frequent temper outbursts and chronic irritability. As compared
to children who did not present with DMDD symptoms, these children demonstrated
more aggression and emotional reactivity and lower receptive language skills,
with high rates of comorbidity with the disruptive behavior disorders. Findings
contribute to an emerging literature on preschool DMDD, with implications for
early childhood psychiatric assessment and clinical interventions.
PMID- 27510440
TI - Can't Stand the Pressure: The Association Between Unprotected Standing, Walking,
and Wound Healing in People With Diabetes.
AB - OBJECTIVE: The objective was to report patterns of physical activity and their
relationship to wound healing success in patients with diabetic foot ulcers
protected with removable or irremovable offloading devices. METHODS: Forty-nine
people with diabetic foot ulcers were randomized to wear either a removable cast
walker (RCW) or an irremovable instant total contact cast (iTCC). Primary outcome
measures included change in wound size, physical activities including position
(ie, sitting, standing, lying) and locomotion (speed, steps, etc). Outcomes
parameters were assessed on weekly basis until wound healing or until 12 weeks.
RESULTS: A higher proportion of patients healed at 12 weeks in the iTCC group ( P
= .038). Significant differences in activity were observed between groups
starting at week 4. RCW patients became more active than the iTCC group (75%
higher duration of standing, 100% longer duration of walking, and 126% longer
unbroken walking bout, P < .05). Overall, there was an inverse association
between rate of weekly wound healing and number of steps taken per day ( r <
.33, P < .05) for both groups. RCW patients had a significant inverse correlation
between duration of daily standing and weekly rate of healing ( r = -.67, P <
.05). Standing duration was the only significant predictor of healing at 12
weeks. CONCLUSION: The results from this study suggest significant differences in
activity patterns between removable and irremovable offloading devices. These
patterns appear to start diverging at week 4, which may indicate a decline in
adherence to offloading. Results suggest that while walking may delay wound
healing, unprotected standing might be an even more unrealized and sinister
culprit.
PMID- 27510441
TI - Description of a New Predictive Modeling Approach That Correlates the Risk and
Associated Cost of Well-Defined Diabetes-Related Complications With Changes in
Glycated Hemoglobin (HbA1c).
AB - The modeling approach described here is designed to support the development of
spreadsheet-based simple predictive models. It is based on 3 pillars: association
of the complications with HbA1c changes, incidence of the complications, and
average cost per event of the complication. For each pillar, the goal of the
analysis was (1) to find results for a large diversity of populations with a
focus on countries/regions, diabetes type, age, diabetes duration, baseline HbA1c
value, and gender; (2) to assess the range of incidences and associations
previously reported. Unlike simple predictive models, which mostly are based on
only 1 source of information for each of the pillars, we conducted a
comprehensive, systematic literature review. Each source found was thoroughly
reviewed and only sources meeting quality expectations were considered. The
approach allows avoidance of unintended use of extreme data. The user can utilize
(1) one of the found sources, (2) the found range as validation for the found
figures, or (3) the average of all found publications for an expedited estimate.
The modeling approach is intended for use in average insulin-treated diabetes
populations in which the baseline HbA1c values are within an average range (6.5%
to 11.5%); it is not intended for use in individuals or unique diabetes
populations (eg, gestational diabetes). Because the modeling approach only
considers diabetes-related complications that are positively associated with
HbA1c decreases, the costs of negatively associated complications (eg, severe
hypoglycemic events) must be calculated separately.
PMID- 27510442
TI - Real-World Use of Open Source Artificial Pancreas Systems.
PMID- 27510443
TI - SPECTRUM.
AB - BACKGROUND: Optimal usage of continuous glucose monitoring (CGM) requires
adequate training of the users. Providing patients with a CGM system without such
a training usually doesn't lead to the intended improvement in metabolic control.
METHODS: In Germany we developed a structured training program ("SPECTRUM") to
ensure a high quality standard for the use of CGM systems. RESULTS: This program
is suitably for patients of all age groups and is applicable to all CGM systems
and all forms of insulin therapy. A curriculum was also developed so that
training centers with less experience with CGM could become capable of offering
comprehensive CGM training. CONCLUSIONS: We believe that usage of such a program
can be an important step forward in achieving more widespread acceptance and use
of CGM systems. Translations in other languages and evaluation with a controlled
clinical trial are planned.
PMID- 27510444
TI - Microvascular hemodynamics in the chick chorioallantoic membrane.
AB - OBJECTIVE: The microvasculature of the CAM in the developing chick embryo is
characterized by interdigitating arteriolar and venular trees, connected at
multiple points along their lengths to a mesh-like capillary plexus. Theoretical
modeling techniques were employed to investigate the resulting hemodynamic
characteristics of the CAM. METHODS: Based on previously obtained anatomical
data, a model was developed in which the capillary plexus was treated as a porous
medium. Supply of blood from arterioles and drainage into venules were
represented by distributions of flow sources and sinks. Predicted flow velocities
were compared with measurements in arterioles and venules obtained via video
microscopy. RESULTS: If it was assumed that blood flowed into and out of the
capillary plexus only at the ends of terminal arterioles and venules, the
predicted velocities increased with decreasing diameter in vessels below 50 MUm
in diameter, contrary to the observations. Distributing sources/sinks along
arterioles/venules led to velocities consistent with the data. CONCLUSIONS: These
results imply that connections to the capillary plexus distributed along the
arterioles and venules strongly affect the hemodynamic characteristics of the
CAM. The theoretical model provides a basis for quantitative simulations of
structural adaptation in CAM networks in response to hemodynamic stimuli.
PMID- 27510445
TI - Biomedical event trigger detection by dependency-based word embedding.
AB - BACKGROUND: In biomedical research, events revealing complex relations between
entities play an important role. Biomedical event trigger identification has
become a research hotspot since its important role in biomedical event
extraction. Traditional machine learning methods, such as support vector machines
(SVM) and maxent classifiers, which aim to manually design powerful features fed
to the classifiers, depend on the understanding of the specific task and cannot
generalize to the new domain or new examples. METHODS: In this paper, we propose
an approach which utilizes neural network model based on dependency-based word
embedding to automatically learn significant features from raw input for trigger
classification. First, we employ Word2vecf, the modified version of Word2vec, to
learn word embedding with rich semantic and functional information based on
dependency relation tree. Then neural network architecture is used to learn more
significant feature representation based on raw dependency-based word embedding.
Meanwhile, we dynamically adjust the embedding while training for adapting to the
trigger classification task. Finally, softmax classifier labels the examples by
specific trigger class using the features learned by the model. RESULTS: The
experimental results show that our approach achieves a micro-averaging F1 score
of 78.27 and a macro-averaging F1 score of 76.94 % in significant trigger
classes, and performs better than baseline methods. In addition, we can achieve
the semantic distributed representation of every trigger word.
PMID- 27510446
TI - Accurate and consistent automatic seismocardiogram annotation without concurrent
ECG.
AB - Seismocardiography (SCG) is the measurement of vibrations in the sternum caused
by the beating of the heart. Precise cardiac mechanical timings that are easily
obtained from SCG are critically dependent on accurate identification of fiducial
points. So far, SCG annotation has relied on concurrent ECG measurements. An
algorithm capable of annotating SCG without the use any other concurrent
measurement was designed. We subjected 18 participants to graded lower body
negative pressure. We collected ECG and SCG, obtained R peaks from the former,
and annotated the latter by hand, using these identified peaks. We also annotated
the SCG automatically. We compared the isovolumic moment timings obtained by hand
to those obtained using our algorithm. Mean +/- confidence interval of the
percentage of accurately annotated cardiac cycles were [Formula: see text],
[Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see
text] for levels of negative pressure 0, -20, -30, -40, and -50 mmHg. LF/HF
ratios, the relative power of low-frequency variations to high-frequency
variations in heart beat intervals, obtained from isovolumic moments were also
compared to those obtained from R peaks. The mean differences +/- confidence
interval were [Formula: see text], [Formula: see text], [Formula: see text],
[Formula: see text], and [Formula: see text] for increasing levels of negative
pressure. The accuracy and consistency of the algorithm enables the use of SCG as
a stand-alone heart monitoring tool in healthy individuals at rest, and could
serve as a basis for an eventual application in pathological cases.
PMID- 27510447
TI - Kicking the tyres of a heart failure trial: physician response to the approval of
sacubitril/valsartan in the USA.
AB - Angiotensin receptor-neprilysin inhibition has been shown to be superior to
target doses of an ACE inhibitor in reducing the risk of cardiovascular death and
clinical disease progression in patients with chronic heart failure and a reduced
EF. Nevertheless, although sacubitril/valsartan has been available in the USA for
a year, uptake of the drug by practitioners has been slow, in part because of
misconceptions about the pivotal trial that demonstrated its efficacy in heart
failure (PARADIGM-HF). This review addresses questions that have been raised in
the USA about the design of the trial as well as the patients who were studied,
the replicability and applicability of the results, and the safety of neprilysin
inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an
appropriate comparator; enrolled patients typical of those seen in the community
with mild to moderate symptoms; yielded highly persuasive and replicable results;
and demonstrated benefits that are applicable to patients taking subtarget doses
of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the
established advantages of sacubitril/valsartan on cardiovascular death and
disease progression outweighed hypothetical uncertainties about the long-term
effects of neprilysin inhibition in patients who might not have survived without
the drug. Accordingly, both the new US and European Society of Cardiology heart
failure guidelines recommend sacubitril/valsartan as the preferred approach to
inhibiting the renin-angiotensin system in patients with chronic heart failure
who are currently receiving an ACE inhibitor or ARB.
PMID- 27510448
TI - CircRNA-protein complexes: IMP3 protein component defines subfamily of circRNPs.
AB - Circular RNAs (circRNAs) constitute a new class of noncoding RNAs in higher
eukaryotes generated from pre-mRNAs by alternative splicing. Here we investigated
in mammalian cells the association of circRNAs with proteins. Using glycerol
gradient centrifugation, we characterized in cell lysates circRNA-protein
complexes (circRNPs) of distinct sizes. By polysome-gradient fractionation we
found no evidence for efficient translation of a set of abundant circRNAs in HeLa
cells. To identify circRNPs with a specific protein component, we focused on IMP3
(IGF2BP3, insulin-like growth factor 2 binding protein 3), a known tumor marker
and RNA-binding protein. Combining RNA-seq analysis of IMP3-co-immunoprecipitated
RNA and filtering for circular-junction reads identified a set of IMP3-associated
circRNAs, which were validated and characterized. In sum, our data suggest that
specific circRNP families exist defined by a common protein component. In
addition, this provides a general approach to identify circRNPs with a given
protein component.
PMID- 27510449
TI - Increased serum levels of vascular endothelial growth factor in pemphigus
foliaceus patients with erythroderma.
AB - BACKGROUND: Erythroderma is a clinical skin syndrome shared by patients with
cutaneous disorders of distinct aetiologies as a result of the combined actions
of chemokines, adhesion molecules, and cytokines, such as vascular endothelial
growth factor (VEGF). OBJECTIVE: To evaluate the profile of serum levels of VEGF
and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1) in pemphigus
foliaceus (PF) patients with erythroderma. METHODS: We conducted a retrospective
study, which included (i) a chart review of all PF patients from the Autoimmune
Blistering Clinic, University of Sao Paulo, Brazil, from January 1991 to December
2014, together with an evaluation of demographic variables, hospitalization
duration and complications and (ii) analysis of the circulating VEGF and sVEGFR-1
levels in PF patients with erythroderma by ELISA. The controls included patients
with pemphigus vulgaris or psoriasis. RESULTS: We observed higher serum VEGF
levels in PF patients during erythroderma than during the non-erythrodermic
phase. PF patients showed increased serum levels of sVEGFR-1 during the
erythrodermic phase in comparison to controls. Interestingly, the sVEGFR-1 and
antidesmoglein-1 levels were positively correlated during the non-erythrodermic
period. CONCLUSION: Erythroderma, which represents one clinical form of PF,
implies more severe outcomes. The circulating levels of VEGF, a potent
endothelial activator, are increased in PF patients with erythroderma; this
result suggests the contribution of the blood vessel endothelium to the
pathogenesis of this clinical syndrome. Interestingly, our findings showed a
positive correlation between the sVEGFR-1 and antidesmoglein-1 antibody levels,
indicating a suppressive response to VEGF augmentation during the erythrodermic
phase of PF.
PMID- 27510450
TI - Epidermal growth factor receptor expression is associated with poor outcome in
cutaneous squamous cell carcinoma.
AB - BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most frequent
cancer in humans after basal cell carcinoma, and its incidence is dramatically
rising. CSCC is rarely problematic, but given its high frequency, the absolute
number of complicated cases is also high. It is necessary to identify molecular
markers in order to recognize those CSCCs with poor prognosis. There is
controversy concerning the role of epidermal growth factor receptor (EGFR) as a
marker of prognosis in CSCC. In addition, EGFR-targeted therapies have emerged in
recent years and a better understanding of the role of EGFR in CSCC may be of
help for some patients in predicting prognosis and guiding curative management.
OBJECTIVES: To evaluate the role of EGFR as a prognostic factor in CSCC. METHODS:
We evaluated clinical and histopathological features, including events of poor
clinical evolution, in a series of 94 cases of CSCC. We also analysed EGFR
expression by immunohistochemistry, fluorescent in situ hybridization and
quantitative polymerase chain reaction. RESULTS: We detected EGFR in 85 cases
(90%), with overexpression in 33 cases (35%), and aberrant EGFR expression in the
cytoplasm in 50 cases (53%). EGFR overexpression in the primary tumours was
associated with lymph node progression, tumour-nodes-metastasis stage progression
and proliferation (Ki-67 staining) in CSCC. EGFR overexpression and poor grade of
differentiation were the strongest independent variables defining lymph node
metastasis and progression in CSCC in a logistic regression model. CONCLUSIONS:
We demonstrate that EGFR overexpression has prognostic implications associated
with lymph node metastasis and progression in CSCC.
PMID- 27510452
TI - Supportive Care: Time to Change Our Prognostic Tools and Their Use in CKD.
AB - In using a patient-centered approach, neither a clinician nor a prognostic score
can predict with absolute certainty how well a patient will do or how long he
will live; however, validated prognostic scores may improve accuracy of
prognostic estimates, thereby enhancing the ability of the clinicians to
appreciate the individual burden of disease and the prognosis of their patients
and inform them accordingly. They may also facilitate nephrologist's
recommendation of dialysis services to those who may benefit and proposal of
alternative care pathways that might better respect patients' values and goals to
those who are unlikely to benefit. The purpose of this article is to discuss the
use as well as the limits and deficiencies of currently available prognostic
tools. It will describe new predictors that could be integrated in future scores
and the role of patients' priorities in development of new scores. Delivering
patient-centered care requires an understanding of patients' priorities that are
important and relevant to them. Because of limits of available scores, the
contribution of new prognostic tools with specific markers of the trajectories
for patients with CKD and patients' health reports should be evaluated in
relation to their transportability to different clinical and cultural contexts
and their potential for integration into the decision-making processes. The
benefit of their use then needs to be quantified in clinical practice by outcome
studies including health-related quality of life, patient and caregiver
satisfaction, or utility for improving clinical management pathways and tailoring
individualized patient-centered strategies of care. Future research also needs to
incorporate qualitative methods involving patients and their caregivers to better
understand the barriers and facilitators to use of these tools in the clinical
setting. Information given to patients should be supported by a more realistic
approach to what dialysis is likely to entail for the individual patient in terms
of likely quality and quantity of life according to the patient's values and
goals and not just the possibility of life prolongation.
PMID- 27510453
TI - Supportive Care: Comprehensive Conservative Care in End-Stage Kidney Disease.
AB - Comprehensive conservative (nondialytic) kidney care is widely recognized and
delivered but until recently, has not been clearly defined. We provide a clear
definition of comprehensive conservative care. This includes interventions to
delay progression of kidney disease and minimize complications as well as
detailed communication, shared decision making, advance care planning, and
psychologic and family support. It does not include dialysis. Limited
epidemiologic evidence from Australia and Canada indicates that, for every new
person diagnosed with ESRD who receives dialysis or transplant, there is one new
person who is managed conservatively (either actively or not). For older patients
(those >75 or 80 years old) who have higher levels of comorbidity (such as
diabetes and heart disease) and poorer functional status, the survival advantage
of dialysis may be limited, and comprehensive conservative management may be
considered; however, robust comparative evidence remains limited. Considerations
of symptoms, quality of life, and hospital-free days are as or sometimes more
important for patients and families than survival. There is some evidence that
communication about possible conservative management options is generally
insufficient, even where comprehensive conservative care pathways are already
established. Symptom control and the cost-effectiveness of interventions are
addressed in the companion papers within this Moving Points in Nephrology series.
There is almost no evidence about which models of care and which interventions
might be most beneficial in this population; future research on these areas is
much needed. Meanwhile, consistency in definition of comprehensive conservative
care and basing interventions on existing evidence about survival, symptoms,
quality of life, and experience will maximize patient-centered and holistic care.
PMID- 27510454
TI - Supportive Care: Integration of Patient-Centered Kidney Care to Manage Symptoms
and Geriatric Syndromes.
AB - Dialysis care is often associated with poor outcomes including low quality of
life (QOL). To improve patient-reported outcomes, incorporation of the patient's
needs and perspective into the medical care they receive is essential. This
article provides a framework to help clinicians integrate symptom assessment and
other measures such as QOL and frailty scores into a clinical approach to the
contemporary supportive care of patients with advanced CKD. This approach
involves (1) defining our understanding of kidney supportive care, patient
centered dialysis, and palliative dialysis; (2) understanding and recognizing
common symptoms associated with advanced CKD; (3) discussing the concepts of
physical function, frailty, and QOL and their role in CKD; and (4) identifying
the structural and process barriers that may arise when patient-centered dialysis
is being introduced into clinical practice.
PMID- 27510455
TI - Supportive Care: Economic Considerations in Advanced Kidney Disease.
AB - Kidney supportive care describes multiple interventions for patients with
advanced CKD that focus on improving the quality of life and addressing what
matters most to patients. This includes shared decision making and aligning
treatment plans with patient goals through advance care planning and providing
relief from pain and other distressing symptoms. Kidney supportive care is an
essential component of quality care throughout the illness trajectory. However,
in the context of limited health care resources, evidence of its cost
effectiveness is required to support decisions regarding appropriate resource
allocation. We review the literature and outline the evidence gaps and particular
issues associated with measuring the costs, benefits, and cost-effectiveness of
kidney supportive care. We find evidence that the dominant evaluative framework
of a cost per quality-adjusted life year may not be suitable for evaluations in
this context and that relevant outcomes may include broader measures of patient
wellbeing, having care aligned with treatment preferences, and family
satisfaction with the end of life care experience. To improve the evidence base
for the cost-effectiveness of kidney supportive care, large prospective cohort
studies are recommended to collect data on both resource use and health outcomes
and should include patients who receive conservative kidney management without
dialysis. Linkage to administrative datasets, such as Medicare, Hospital Episode
Statistics, and the Pharmaceutical Benefits Scheme for prescribed medicines, can
provide a detailed estimate of publicly funded resource use and reduce the burden
of data collection for patients and families. Longitudinal collection of quality
of life and functional status should be added to existing cohort or kidney
registry studies. Interventions that improve health outcomes for people with
advanced CKD, such as kidney supportive care, not only have the potential to
improve quality of life, but also may reduce the high costs associated with
unwanted hospitalization and intensive medical treatments.
PMID- 27510457
TI - Structural mechanics and helical geometry of thin elastic composites.
AB - Helices are ubiquitous in nature, and helical shape transition is often observed
in residually stressed bodies, such as composites, wherein materials with
different mechanical properties are glued firmly together to form a whole body.
Inspired by a variety of biological examples, the basic physical mechanism
responsible for the emergence of twisting and bending in such thin composite
structures has been extensively studied. Here, we propose a simplified analytical
model wherein a slender membrane tube undergoes a helical transition driven by
the contraction of an elastic ribbon bound to the membrane surface. We
analytically predict the curvature and twist of an emergent helix as functions of
differential strains and elastic moduli, which are confirmed by our numerical
simulations. Our results may help understand shapes observed in different
biological systems, such as spiral bacteria, and could be applied to novel
designs of soft machines and robots.
PMID- 27510456
TI - Supportive Care: Communication Strategies to Improve Cultural Competence in
Shared Decision Making.
AB - Historic migration and the ever-increasing current migration into Western
countries have greatly changed the ethnic and cultural patterns of patient
populations. Because health care beliefs of minority groups may follow their
religion and country of origin, inevitable conflict can arise with decision
making at the end of life. The principles of truth telling and patient autonomy
are embedded in the framework of Anglo-American medical ethics. In contrast, in
many parts of the world, the cultural norm is protection of the patient from the
truth, decision making by the family, and a tradition of familial piety, where it
is dishonorable not to do as much as possible for parents. The challenge for
health care professionals is to understand how culture has enormous potential to
influence patients' responses to medical issues, such as healing and suffering,
as well as the physician-patient relationship. Our paper provides a framework of
communication strategies that enhance crosscultural competency within nephrology
teams. Shared decision making also enables clinicians to be culturally competent
communicators by providing a model where clinicians and patients jointly consider
best clinical evidence in light of a patient's specific health characteristics
and values when choosing health care. The development of decision aids to include
cultural awareness could avoid conflict proactively, more productively address it
when it occurs, and enable decision making within the framework of the patient
and family cultural beliefs.
PMID- 27510458
TI - Visualization of the Intimal Flap in Intracranial Arterial Dissection Using High
Resolution 3T MRI.
AB - BACKGROUND AND PURPOSE: Presence of an intimal flap is a critical imaging finding
in diagnosing intracranial artery dissection (ICAD). Recent reports showed that
high-resolution magnetic resonance imaging (MRI) was better at identifying
intimal flaps as compared with routine MRI techniques used in clinical settings.
However, no current standardized sequence for high-resolution MRI without
gadolinium enhancement produces images of satisfactory quality with clinically
tolerable scanning times. This study evaluated a nonenhanced high-resolution fast
spin echo (HR-FSE) MRI sequence for visualizing intimal flaps in patients with
ICAD. SUBJECTS AND METHODS: Three patients with ICAD underwent plain MRI
examination using a 2-dimensional T2-weighted FSE imaging sequence optimized for
our 3T system (in-plane pixel size, .23 mm * .23 mm; slice thickness 3 mm with no
interslice gap), as well as scanning with conventional modalities, including CT
angiography, magnetic resonance angiography, and digital subtraction angiography.
We assessed whether these imaging methods could visualize an intimal flap and/or
double lumen sign in the participants and compared the results between HR-FSE and
the other modalities. RESULTS: HR-FSE images clearly showed intimal flaps and
double lumen signs in all 3 patients, whereas the conventional modalities
identified a double lumen sign in only 2 of the 3 patients. CONCLUSIONS: The
present method of optimized HR-FSE imaging with a 3T system improved
visualization of intimal flaps and should thus be considered for assessing
patients with suspected ICAD that cannot be definitively diagnosed by
conventional imaging modalities.
PMID- 27510459
TI - Reprogramming A375 cells to induced-resembled neuronal cells by structured
overexpression of specific transcription genes.
AB - Induced-resembled neuronal cells (irNCs) are generated by reprogramming human
melanoma cells through the introduction of key transcription factors, providing
novel concepts in the treatment of malignant tumor cells and making it possible
to supply neural cells for laboratory use. In the present study, irNCs were
derived from A375 cells by inducing the 'forced' overexpression of specific
genes, including achaete-scute homolog 1 (Ascl1), neuronal differentiation factor
1 (Neurod1), myelin transcription factor 1 (Myt1), brain protein 2 (Brn2, also
termed POU3F2) and human brain-derived neurotrophic factor (h-BDNF). irNCs
induced from A375 cells express multiple neuronal markers and fire action
potentials, exhibiting properties similar to those of motor neurons. The
reprogramming procedure comprised reverse transcription-polymerase chain reaction
and immunofluorescence staining; furthermore, electrophysiological profiling
demonstrated the characteristics of the induced-resembled neurons. The present
study obtained a novel type of human irNC from human melanoma, which secreted
BDNF continuously, providing a model for neuron-like cells. Thus, irNCs offer
promise in investigating various neural diseases by using neural-like cells
derived directly from the patient of interest.
PMID- 27510460
TI - Bis(allyl)-ruthenium(iv) complexes with phosphinous acid ligands as catalysts for
nitrile hydration reactions.
AB - Several mononuclear ruthenium(iv) complexes with phosphinous acid ligands
[RuCl2(eta(3):eta(3)-C10H16)(PR2OH)] have been synthesized (78-86% yield) by
treatment of the dimeric precursor [{RuCl(MU-Cl)(eta(3):eta(3)-C10H16)}2] (C10H16
= 2,7-dimethylocta-2,6-diene-1,8-diyl) with 2 equivalents of different aromatic,
heteroaromatic and aliphatic secondary phosphine oxides R2P([double bond, length
as m-dash]O)H. The compounds [RuCl2(eta(3):eta(3)-C10H16)(PR2OH)] could also be
prepared, in similar yields, by hydrolysis of the P-Cl bond in the corresponding
chlorophosphine-Ru(iv) derivatives [RuCl2(eta(3):eta(3)-C10H16)(PR2Cl)]. In
addition to NMR and IR data, the X-ray crystal structures of representative
examples are discussed. Moreover, the catalytic behaviour of complexes
[RuCl2(eta(3):eta(3)-C10H16)(PR2OH)] has been investigated for the selective
hydration of organonitriles in water. The best results were achieved with the
complex [RuCl2(eta(3):eta(3)-C10H16)(PMe2OH)], which proved to be active under
mild conditions (60 degrees C), with low metal loadings (1 mol%), and showing
good functional group tolerance.
PMID- 27510461
TI - Silencing KRAS Overexpression in Cadmium-Transformed Prostate Epithelial Cells
Mitigates Malignant Phenotype.
AB - Cadmium (Cd) is a potential human prostate carcinogen. Chronic Cd exposure
malignantly transforms RWPE-1 human prostate epithelial cells into CTPE cells by
an unclear mechanism. Previous studies show that RWPE-1 can also be malignantly
transformed by arsenic, and KRAS activation is key to causation and maintenance
of this phenotype. Although Cd and arsenic can both transform prostate epithelial
cells, it is uncertain whether their mechanisms are similar. Thus, here we
determined whether KRAS activation is critical in causing and maintaining Cd
induced malignant transformation in CTPE cells. Expression of KRAS, miRNAs, and
other genes of interest was analyzed by Western blot and RT-PCR. Following stable
KRAS knockdown (KD) by RNA interference using shRNAmir, the malignant phenotype
was assessed by various physical and genetic parameters. CTPE cells greatly
overexpressed KRAS by 20-fold, indicating a likely role in Cd transformation.
Thus, we attempted to reverse the malignant phenotype via KRAS KD. Two weeks
after shRNAmir transduction, KRAS protein was undetectable in CTPE KD cells,
confirming stable KD. KRAS KD reduced stimulated RAS/ERK and PI3K/AKT signaling
pathways and markedly mitigated multiple physical and molecular malignant cell
characteristics including: hypersecretion of MMP-2, colony formation, cell
survival, and expression of cancer-relevant genes (reduced proliferation and cell
cycle-related genes; activated tumor suppressor PTEN). However, KRAS KD did not
reverse miRNA expression originally down-regulated by Cd transformation. These
data strongly suggest KRAS is a key gene in development and maintenance of the Cd
induced malignant phenotype, at least in the prostate. It is not, however, the
only genetic factor sustaining this phenotype.
PMID- 27510462
TI - Validation of RPS13 as a reference gene for absolute quantification of SIV RNA in
tissue of rhesus macaques.
AB - Persistent HIV reservoirs and the absolute quantification of viral RNA copies in
tissues have become a prominent focus of multiple areas ofHIV/SIV research.
Absolute quantification of viral RNA via reverse transcription, quantitative PCR
(RT-qPCR) necessitates the use of an appropriate RNA reference gene whose
expression is unaffected by both experimental and confounding conditions. In this
study, we demonstrate the utility of ribosomal protein S13 mRNA (RPS13) as a
stable, medium abundance reference gene for RT-qPCR normalization of HIV/SIV RNA
copy number. We developed a RPS13 RNA standard assay utilizing an in vitro RNA
transcript for normalization of absolute SIV RNA quantities in tissues
reservoirs. The RT-qPCR assay showed a high degree of repeatability and
reproducibility across RNA levels appropriate for absolute SIV quantification. In
assessing the utility of RPS13 as a reference gene, limited variation in the
absolute, inter-tissue quantities of RPS13 mRNA was observed within multiple
tissue samples obtained from rhesus macaques (average CV=2.86%). We demonstrate
rhesus macaque RPS13 mRNA expression is not affected by alcohol administration,
SIV infection, or antiviral therapy (PMPA/FTC). Additionally, assay functionality
was validated for normalization of SIV copy number using cellular RNA prepared
from samples of variable RNA integrity. RPS13 is a suitable reference gene for
normalization of absolute SIV RNA quantities in tissues and is most appropriate
for intra-tissue or similar tissue type comparisons of SIV copy number.
PMID- 27510463
TI - Same-day discharge after craniotomy for supratentorial tumour surgery: a
retrospective observational single-centre study.
AB - PURPOSE: Enhanced Recovery After Surgery is a multimodal perioperative care
pathway designed to achieve early discharge in patients undergoing major surgery.
Recent advances in neurosurgery allow for shorter duration of anesthesia and
surgery, faster recovery, and earlier discharge from hospital. The purpose of
this retrospective observational study was to assess the incidence of early
discharge from hospital in patients undergoing craniotomy for supratentorial
brain tumours as well as to explore the associated perioperative factors,
anesthesia techniques, and complications. METHODS: The medical records of all
patients who underwent craniotomy (less than four-hour duration) for
supratentorial tumour over a five-year period were retrospectively reviewed. The
data analyzed included the postoperative discharge destination, type of
anesthesia-i.e., general anesthesia (GA) vs awake craniotomy (AC), and the
incidence of adverse events. RESULTS: Data from 329 patients [mean (SD) age 48
(12) yr; 164 male, 165 female] were analyzed, including 198 (AC, n = 157; GA, n =
41) patients who were preoperatively scheduled for same-day discharge. Successful
same-day discharge occurred in 175/198 (88.4%) of these patients (AC, n = 139;
GA, n = 36). Five (2.9%) of the 175 patients (4 AC, 1 GA) with same-day discharge
required readmission to hospital within the first 12 hr after discharge. Six
(1.8%) of the 329 total patients had a documented postoperative intracranial
bleed, but none occurred after initial discharge from hospital. CONCLUSION: Same
day discharge from hospital is possible in carefully selected patients after both
GA and AC for supratentorial tumour surgery.
PMID- 27510464
TI - Revisiting the consequences of inadequate Canadian physician resource planning: a
renewed call to action.
PMID- 27510465
TI - Capsule Commentary on Nicolaidis et al., The Development and Evaluation of an
Online Healthcare Toolkit for Autistic Adults and their Primary Care Providers.
PMID- 27510466
TI - Lipid profiling of cyanobacteria Synechococcus sp. PCC 7002 using two-dimensional
liquid chromatography with quadrupole time-of-flight mass spectrometry.
AB - Glycerolipid is a main component of membranes in oxygenic photosynthetic
organisms. Up to now, the majority of publication in this area has focused on the
physiological functions of glycerolipids and lipoprotein complexes in
photosynthesis, but the study on the separation and identification of
glycerolipids in thylakoid membrane in cyanobacteria is relatively rare. Here we
report a new method to separate and identify five photosynthetic glycerolipid
classes, including monoglucosyl diacylglycerol, monogalactosyl diacylglycerol,
digalactosyl diacylglycerol, sulfoquinovosyl diacylglycerol, and
phosphatidylglycerol, in cyanobacteria Synechococcus sp. PCC 7002 by two
dimensional (normal- and reversed-phase) liquid chromatography online coupled to
quadrupole time-of-flight mass spectrometry. Over twice as many lipid species
were detected by our method compared to the previously reported methods. Ten new
odd-chain fatty acid glycerolipids were discovered for the first time. Moreover,
complete separation of isomers of monogalactosyl diacylglycerol and monoglucosyl
diacylglycerol was achieved. According to the tandem mass spectrometry results,
we found that the head group of monoglucosyl diacylglycerols was not as stable as
that of monogalactosyl diacylglycerols, which might explain why the organism
chose monogalactosyl diacylglycerols and digalactosyl diacylglycerols instead of
monoglucosyl diacylglycerols as the main content of the photosynthetic membranes
in the history of evolution. This work will benefit further research on the
physiological function of glycerolipids.
PMID- 27510467
TI - Primary female breast sarcoma: clinicopathological features, treatment and
prognosis.
AB - Primary breast sarcoma (PBS) is a rare and heterogeneous group of malignancies
with limited publications. We obtained data from the Surveillance, Epidemiology,
and End Results Program and performed analysis to determine clinicopathological
characteristics of PBS and estimate their associations with overall survival (OS)
and cancer-specific survival (CSS). Median age of PBS was 55-59 years and median
OS was 108 months. Age, overlap or entire breast involvement, tumor histology,
and tumor spread were associated with poor survival outcomes. In the
multivariable analysis, tumor size, lymph node involvement, distant metastasis
and histologic grade were correlated with survival outcomes (P < 0.001). In M0
patients, mastectomy was associated with worse survival outcomes compared with
breast conservative surgery (BCS) (adjusted hazard ratio [adjHR], 1.80; 95% CI,
1.31-2.47), regardless of tumor size, tumor grade, tumor histology or radiation
history. Adjuvant radiation improved survival outcomes in patients with tumor
size >5 cm (adjHR, 0.63; 95% CI, 0.43-0.91), but not in patients with tumor size
<= 5 cm. Our study demonstrated clinicopathological characteristics of PBS in the
US population and supports performing BCS if R0 resection can be achieved, with
radiation if tumor size is over 5 cm.
PMID- 27510468
TI - [Not Available].
PMID- 27510469
TI - Accelerated hydration reaction of an unsymmetrical tolan evidenced by a Hg(ii)
trapped macrocycle and its application as a Hg(ii)-selective indicator.
AB - Hg(ii)-mediated hydration reactions of unsymmetrical quinoline type tolans were
studied. The observed accelerated reactions of the tolans rely on the additional
binding motifs of the tolan, as supported by the X-ray structure of the
macrocycle (2b). The analyte-specific reaction allows us to detect Hg(ii) in
buffered media.
PMID- 27510470
TI - Preoperative Echocardiography Examination of Right Ventricle Function in Patients
Scheduled for LVAD Implantation Correlates with Postoperative Hemodynamic
Examinations.
AB - BACKGROUND Left ventricular assist devices (LVAD) are used to treat heart
failure. Preoperative prediction of RV function after LVAD implantation is
crucial. Correlations were found between preoperative echo and RV function after
LVAD implantation. MATERIAL AND METHODS We retrospectively reviewed 23 male
patients (8 ischemic, 15 nonischemic cardiomyopathy) with LVAD implantation (17
HeartWare, 6 HeartMate II) at the Silesian Center for Heart Diseases from 1
January 2013 to 28 October 2014. Preoperative TTE data of RV function included
RVFAC (fractional area change), TAPSE (tricuspid annulus plane systolic
excursion), RV diameter (RV4), and RV/LV (right/left ventricle) ratio.
Postoperative hemodynamic mean pulmonary pressure (mPAP), central venous pressure
(CVP), cardiac output (CO), and cardiac index (CI) were measured and recorded
every 2 h up to 10 days (1, 2, ...120) and correlated. Study endpoints were
mortality, discharge from ICU, and RV dysfunction. RESULTS There were no RV
dysfunctions. Correlations of CO and CI with RV4 and RV/LV ratio were
significantly positive at many time points, with TAPSE and FAC positive or
negative. Correlations mPAP with RV4 were significantly positive: 1, 2, 3, 7, 8,
57, 58, 59. With RV/LV ratio positive: 44, 47, with TAPSE in 36. With FAC
positive 11, 13-15, 22 and negative 57. Correlations CVP with RV4 were negative,
with positive significance in 1, 52. With RV/LV ratio positively 52, 54, 56 and
negative 71, 72, 73. With TAPSE were negative significantly: 30, 68. With FAC
positive 11, 12, 13, 14 and negative: 68. CONCLUSIONS RV4 and RV/LV ratio before
LVAD implantation are more predictive for postoperative RV function than RVFAC
and TAPSE, probably because RVFAC and TAPSE are load-dependent.
PMID- 27510471
TI - Utility of thyroid testing in the ED.
PMID- 27510472
TI - Subtle presentation of herpes simplex encephalitis.
PMID- 27510473
TI - Impact of an emergency medicine pharmacist on time to thrombolysis in acute
ischemic stroke.
PMID- 27510474
TI - Failed Deglutitive Upper Esophageal Sphincter Relaxation Is a Risk Factor for
Aspiration in Stroke Patients with Oropharyngeal Dysphagia.
AB - Background/Aims: We attempted to examine the relationship between abnormal
findings on high-resolution manometry (HRM) and videofluoroscopic swallowing
study (VFSS) of the pharynx and upper esophageal sphincter (UES), and to identify
the risk factors for aspiration. Methods: We performed VFSS and HRM on the same
day in 36 ischemic stroke patients (mean age, 67.5 years) with dysphagia.
Pressure (basal, median intra bolus, and nadir), relaxation time interval of the
UES, and mesopharyngeal and hypopharyngeal contractility (as a contractile
integral) were examined using HRM. The parameters of VFSS were vallecular
residue, pyriform sinus residue, vallecular overflow, penetration, and
aspiration. The association between the parameters of VFSS and HRM was analyzed
by the Student's t test. Results: Three (8.3%) and 4 (11.1%) stroke patients with
dysphagia had pyriform sinus residue and vallecular sinus residue, respectively,
and 5 (13.8%) patients showed aspiration. Mesopharyngeal and hypopharyngeal
contractile integrals in patients with residue in the pyriform sinus were
significantly lower than those in patients without residue in the pyriform sinus
(P < 0.05). Relaxation time intervals in patients with aspiration were
significantly shorter than those in patients without aspiration (P < 0.05), and
multivariate regression analysis revealed a shorter relaxation time interval as
the main risk factor for aspiration (OR, 0.03; 95% CI, 0.01-0.65; P < 0.05).
Conclusions: Manometric measurements of the pharynx and UES were well correlated
with abnormal findings in the VFSS, and a shorter relaxation time interval of the
UES during deglutition is an important parameter for the development of
aspiration.
PMID- 27510475
TI - Advances in the Diagnosis and Treatment of PCOS.
AB - While the Rotterdam criteria look simple and easy to follow, in clinical practice
diagnosis of PCOS may be problematic because of the use of inaccurate commercial
androgen assays. Progresses in ovarian ultrasound and in AMH measurement have
modified the way to make the diagnosis of PCOS and an update of Rotterdam
criteria may be necessary. In classic severe form of PCOS, ovarian follicle count
is a very reliable diagnostic criterion but AMH measurement may also present high
diagnostic specificity and sensitivity. This finding is particularly important
when no clinical signs of androgen excess are present and only commercial assays
for androgen measurement are available. At the contrary, in mild PCOS phenotypes,
sensitivity of AMH measurement is too low whileFNPO count maintains a high
diagnostic sensitivity. However, at least in ovulatory hyperandrogenic PCOS
phenotype, increased AMH values in association with enlarged ovarian size permit
the diagnosis of ovulatory PCOS in 85% of these patients. Treatment of PCOS women
has to be directed to get fertility or in patients not seeking fertility to solve
or attenuate the psychological implications of androgen excess and of irregular
menses and the risk of endometrial hyperplasia. The therapeutic protocols that
are used in our department are presented.
PMID- 27510476
TI - Approaches to Improve Efficiency of Dendritic Cell-based Therapy of High Grade
Gliomas.
AB - High grade gliomas (HGGs) are the most frequent and highly invasive type of brain
tumors, which arise from glial cells. Among HGGs, glioblastoma multiforme (GBM)
is the commonest and deadliest tumor type. Standard HGG therapy that involves
tumor resection followed by concomitant treatment with radiation exposure and
temozolomide (TMZ) cannot prevent recurrent tumor. The median survival of treated
patients after surgery does not exceed 1.5 years. Vaccination with autologous
dendritic cells (DCs) pulsed with tumor-specific peptides, antigens, or lysates
is considered as a promising option to induce a potent anti-tumor immune response
and cytotoxicity against GBM cells. However, since the tumor microenvironment is
highly immunosuppressive and immunotolerant, specialized approaches should be
applied to protect DC transplants against tumor-induced functional impairment and
inhibition. So far, many phase I-III clinical trials utilizing DC vaccines for
HGG treatment were completed or are underway. In summary, DC vaccination was safe
and well tolerated by patients. DC-induced anti-tumor immune responses correlated
with prolonged overall and progression- free survival. Combination of DC therapy
with other interventional strategies (i.e., radiotherapy, chemotherapy,
antibodies, etc.) and multimodal approaches should improve HGG treatment
outcomes. In this review, we consider strategies that provide an option to
override the immune inhibitory tumor microenvironment and boost DC vaccine-based
antitumor immune response.
PMID- 27510477
TI - Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain
Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells.
AB - Recent evidence highlights that energy requirements of cancer cells vary greatly
from normal cells and they exhibit different metabolic phenotypes with variable
participation of both glycolysis and oxidative phosphorylation (OXPHOS).
Interestingly, mitochondrial electron transport chain (ETC) has been identified
as an essential component in bioenergetics, biosynthesis and redox control during
proliferation and metastasis of cancer cells. This dependence converts ETC of
cancer cells in a promising target to design small molecules with anti-cancer
actions. Several small molecules have been described as ETC inhibitors with
different consequences on mitochondrial bioenergetics, viability and
proliferation of cancer cells, when the substrate availability is controlled to
favor either the glycolytic or OXPHOS pathway. These ETC inhibitors can be
grouped as 1) inhibitors of a respiratory complex (e.g. rotenoids, vanilloids,
alkaloids, biguanides and polyphenols), 2) inhibitors of several respiratory
complexes (e.g. capsaicin, ME-344 and epigallocatechin-3 gallate) and 3)
inhibitors of ETC activity (e.g. elesclomol and VLX600). Although pharmacological
ETC inhibition may produce cell death and a decrease of proliferation of cancer
cells, factors such as degree of inhibition of ETC activity by small molecules,
bioenergetic profile and metabolic flexibility of different cancer types or
subpopulations of cells in a particular cancer type, can affect the impact of the
anti-cancer actions. Particularly interesting are the adaptive mechanisms induced
by ETC inhibition, such as induction of glutamine-dependent reductive
carboxylation, which may offer a strategy to sensitize cancer cells to inhibitors
of glutamine metabolism.
PMID- 27510478
TI - Duration of Dual Antiplatelet Therapy After Coronary Stenting.
AB - BACKGROUND: Dual antiplatelet therapy (DAPT) is one of the cornerstones of
coronary artery disease (CAD) treatment. Standard DAPT requires one of, P2Y12
receptor inhibitors, clopidogrel, prasugrel or ticagrelor as an adjunct therapy
to aspirin administration. The decision over DAPT duration depends on the
evaluation of thrombotic risk and the assessment of the probability for major
bleeding events. METHODS: The goal of this work was to identify which would be
the appropriate combination of antiplatelet agents and the optimal duration of
DAPT, based on the patient's medical history and clinical characteristics. A
thorough search of PubMed and the Cochrane Database was conducted in order to
identify randomized controlled trials, observational studies, current ESC and
ACC/AHA guidelines and novel articles on the subject. RESULTS: The decision over
DAPT duration is based on a careful approach which requires the evaluation of
thrombotic risk and the assessment of the probability for major bleeding events.
A series of aspects and special conditions may influence the duration of DAPT
after stenting e.g. the type of the implanted stent (DES or BMS) or if the
commencement of DAPT is administered in the context of an acute coronary syndrome
or in the setting of stable CAD. Current guidelines can assist clinicians in
making decisions but treating patients in special groups e.g. with diabetes
mellitus or the elderly people can be very demanding. CONCLUSION: Studies which
examined optimal DAPT duration, displayed controversial results, mainly observed
because of the discrepancy and heterogeneity between different study designs or
the decision of a great proportion of investigators to statistically test for non
inferiority. A careful, patient-centered approach, which considers thrombotic
risk versus the risk for bleeding complications and other individual
characteristics and comorbidities, is required when deciding DAPT duration.
PMID- 27510479
TI - Carrier Mediated Systemic Delivery of Protein and Peptide Therapeutics.
AB - Over the last few decades proteins and peptide therapeutics have occupied an
enormous fraction of pharmaceutical industry. Despite their high potential as
therapeutics, the big challenge often encountered is the effective administration
and bioavailability of protein therapeutics in vivo system. Peptide molecules are
well known for their in vivo short half-lives. In addition, due to high molecular
weight and susceptibility to enzymatic degradation, often it is not easy to
administer peptides and proteins orally or through any other noninvasive routes.
Conventional drug management system often demands for frequent and regular
interval intravenous/subcutaneous administration, which decreases overall patient
compliance and increases chances of side-effects related to dose-fluctuation in
systemic circulation. A controlled mode of delivery system could address all
these short-comings at a time. Therefore, long-acting sustained release
formulations for both invasive and noninvasive routes are under rigorous study
currently. Long-acting formulations through invasive routes can address patient
compliance and dose-fluctuation issues by less frequent administration. Also, any
new route of administration other than invasive routes will address cost
effectiveness of the therapeutic by lessening the need to deal with health
professional and health care facility. Although a vast number of studies are
dealing with novel drug delivery systems, till now only a handful of controlled
release formulations for proteins and peptides have been approved by FDA. This
study therefore focuses on current and perspective controlled release
formulations of existing and novel protein/peptide therapeutics via conventional
invasive routes as well as potential novel non-invasive routes of administration,
e.g., oral, buccal, sublingual, nasal, ocular, rectal, vaginal and pulmonary.
PMID- 27510480
TI - Adrenal Hyperandrogenism and Polycystic Ovary Syndrome.
AB - BACKGROUND: The prevalence of adrenal hyperandrogenism (AH), as defined by
increased circulating dehydroepiandrosterone-sulfate (DHEAS) levels, ranges from
15 to 45% in women with polycystic ovary syndrome (PCOS). METHODS: The aim of
this review is to update the pathogenesis and consequences of AH in PCOS, from
molecular genetics to the clinical setting. RESULTS: Mounting evidence derived
from animal models suggests that genetically or enviromentally determined
prenatal androgen excess, by influencing the hormonal and metabolic phenotype of
susceptible female fetuses later in life, may be the capital event for the
development of AH in PCOS. Because human placental aromatase activity is likely
to prevent any deleterious effect of maternal hyperandrogenemia on the fetus,
inheritance of the maternal steroidogenic defect is the more likely culprit, even
though other factors such as changes in placental steroidogenesis itself or its
nutritional efflux may also be involved in the building a deregulated enzymatic
pathway from utero to adult life. Anyhow, the most important issue is whether or
not AH influences the cardiometabolic risk of women with PCOS. On the one hand,
AH has shown a controversial relationship with carbohydrate metabolism and
adiposity, and is also associated with abnormalities in blood pressure regulation
in these patients. On the other hand, DHEAS may exert a beneficial effect on the
lipid profile of both lean and obese patients. Lastly, available studies in women
with PCOS cast doubt upon a protective role of DHEAS levels on subclinical
atherosclerosis, despite opposite data from the general population. CONCLUSION:
AH is frequent in patients with PCOS yet unraveling its consequences for the
management of this disorder requires future longitudinal studies.
PMID- 27510481
TI - Hirsutism in Polycystic Ovary Syndrome: Pathophysiology and Management.
AB - BACKGROUND: Hirsutism is defined as the presence of terminal hair with male
distribution in women, and polycystic ovary syndrome (PCOS) is the most common
etiology of hirsutism. METHODS: The aim of this study is to review aspects of
hair growth that are relevant for the understanding of hirsutism in PCOS, along
with current treatment alternatives. RESULTS: The prevalence of hirsutism in PCOS
ranges from 70 to 80%, vs. 4% to 11% in women in the general population.
Hirsutism in PCOS is associated with both ovarianderived androgen excess and
individual sensitivity of the pilosebaceous unit to androgens. Interventions to
decrease hirsutism in PCOS include the suppression of androgen excess by combined
oral contraceptives (OCPs). If OCPs are contraindicated, mainly in the presence
of insulin-resistance related comorbidities, a second-line option for reducing
androgen secretion may be metformin associated with lifestyle changes. Other
interventions should be guided by hirsutism severity, determined by the modified
Ferriman-Gallwey score, and by the amount of distress hirsutism causes to the
patient, and should be maintained for at least 6-12 months. Mild hirsutism is
usually treated with a combination of non-pharmacological methods and OCPs,
whereas moderate and severe hirsutism may require a combination of antiandrogens
and OCPs, or, if OCPs cannot be used, antiandrogens plus a safe contraceptive
method. In all cases, strong clinical support is crucial to ensure treatment
adherence and success. CONCLUSION: The understanding of the pathophysiology of
hirsutism in PCOS, as well as classifying its severity and the distress it causes
to each patient is essential to choose the proper treatment. The presence of
metabolic comorbidities and menstrual disturbances will also guide the
individualized management of hirsutism in women with PCOS.
PMID- 27510482
TI - Insulin Resistance and Polycystic Ovary Syndrome.
AB - BACKGROUND: Insulin resistance and the associated compensatory hyperinsulinemia
are common findings in women with PCOS, and may play a key role in this
condition. METHODS: In this article, we focused on the significance of insulin
resistance in PCOS, reviewing the available literature on epidemiology,
pathogenesis, pathophysiology and treatment of this condition. RESULTS: It has
been estimated that approximately 70% of these women are insulin resistant, but
this figure is affected by frequent referral bias. In addition, there is
metabolic heterogeneity between clinical phenotypes of PCOS. A fundamental issue
is the role that hyperinsulinemia plays in androgen overproduction, which is
enhanced by bidirectional links between insulin resistance and hyperandrogenism.
Available data suggest that women with PCOS may have insulin action alterations
of heterogeneous origins, which induce specific abnormalities in these subjects
due to the presence of intrinsic defects. Obesity is a common finding in these
patients and contributes to the association between PCOS and insulin resistance,
combining with the effect of PCOS per se. Insulin sensitization shows several
beneficial effects in the treatment of this condition. However, clinical response
is heterogeneous. CONCLUSION: Insulin resistance is a common feature of women
with PCOS, although it is not universal and differ between clinical phenotypes of
PCOS. Insulin resistance and hyperandrogenism appear to be interrelated key
factors in the pathogenesis of PCOS. We hypothesize that PCOS might represent a
common end-stage clinical phenotype of different processes, in which there are
impaired insulin action and hyperandrogenism, probably favoured by specific,
intrinsic abnormalities of these women.
PMID- 27510483
TI - Current Insights Into Inositol Isoforms, Mediterranean and Ketogenic Diets for
Polycystic Ovary Syndrome: From Bench to Bedside.
AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex syndrome characterized
by reproductive and metabolic implications. Lifestyle changes, such as diet and
exercise, are considered first-line treatment for women affected by PCOS.
Pharmacologic treatments target the hormonal and metabolic dysregulations
associated to the disease such as insulin resistance, anovulation, hirsutism and
menstrual irregularities. OBJECTIVE: To focus on the role of inositol isoforms,
as well as Mediterranean and ketogenic diets, as possible therapeutic strategies
in PCOS women. METHOD: Narrative overview, synthesizing the findings of
literature retrieved from searches of computerized databases. RESULTS:
Accumulating evidence suggests that two inositol isoforms, myo- and D-chiro-, may
play a pivotal role in re-addressing both hormonal and metabolic parameters
toward homeostasis, counteracting the symptoms and signs typical of this
syndrome. In addition, studies focused on Mediterranean and ketogenic diet
provided positive results in patients affected by obesity and type 2 diabetes, so
these dietetic regimens could represent a fascinating dietetic treatment for the
management of PCOS. CONCLUSION: Both the isoforms of inositol are effective in
improving ovarian function and metabolism in patients with PCOS. In spite of
accumulating evidence, it is currently not possible to draw firm conclusion(s)
about the efficacy of these interventions considering the severe bias due to
different samples size, dose, and duration of intervention among the published
studies on this topic. Furthermore, future longitudinal cohort studies along with
prospective interventional trials may contribute to better clarify the role of
Mediterranean and ketogenic diets in the treatment of PCOS.
PMID- 27510484
TI - Cardiovascular Risk in the Different Phenotypes of Polycystic Ovary Syndrome.
AB - BACKGROUND: The polycystic ovary syndrome (PCOS) is the commonest endocrine
disorder in women of reproductive age and shows substantial phenotypic
variability. According to the presence of the three diagnostic criteria of PCOS,
i.e. oligo- and/or anovulation, hyperandrogenemia and/or clinical signs of high
androgen levels, and polycystic ovaries, four different phenotypes of PCOS are
identified. It appears that these phenotypes differ in the prevalence of several
established and emerging cardiovascular risk factors. METHODS: We searched the
literature for studies that compared the cardiovascular risk profile of patients
with the different phenotypes of PCOS. RESULTS: Patients with both anovulation
and hyperandrogenemia have more pronounced insulin resistance and higher levels
of proinflammatory and prothrombotic mediators than patients with polycystic
ovaries and either anovulation or hyperandrogenemia. CONCLUSION: Given that these
differences appear to be mainly driven by the more pronounced obesity of the
former patients, diet and exercise aiming at weight loss should constitute the
cornerstone of management of PCOS and should be particularly emphasized in
patients with the higher risk phenotypes of the syndrome.
PMID- 27510485
TI - Strategies that Target Tight Junctions for Enhanced Drug Delivery.
AB - Ions and molecules move across epithelial barriers by two pathways, the
transcellular and the paracellular. The former is taken by lipophilic compounds,
or by ions and molecules that move across the plasma membrane through pumps,
carriers or exchangers. The second route is regulated by the tight junction (TJ)
that through paracellular channels, allows the transport of ions across
epithelial barriers. Since, a wide variety of bioactive molecules like peptides,
proteins and oligonucleotides cannot use the transcellular route, due to their
hydrophilic nature, interest has arisen in devising procedures to open the TJ in
a reversible manner for paracellular drug delivery. Here, we describe how
different strategies have been devised to enhance the paracellular intestinal
absorption of drugs; to open the blood-brain barrier (BBB) to allow the
penetration of drugs for the treatment of disorders and tumors of the central
nervous system; or to deliver antigens into the subjacent mucosa associated
lymphoid tissues, for the development of mucosal vaccines. The strategies
described, include the use of peptides, antibodies and miRNAs that target
proteins of the apical junctional complex, as well as toxins derived from
microorganisms that open the TJ by inducing the contraction of the cortical
actomyosin ring. Also, we describe how paracellular absorption, is enhanced by
drugs that extract cholesterol from the plasma membrane, surfactants, fatty
acids, oligosaccharides, cationic polymers, nitric oxide donors and calcium
chelators. Likewise, we explain how the BBB has been opened by employing tumor
necrosis factor-alpha, bradykinin, short chain alkylglycerols, hyperosmotic
mannitol and focused ultrasound.
PMID- 27510486
TI - Structural Aspects of Solid Solutions of Enantiomers.
AB - A mixture of two enantiomers can crystallize according to three types of
heterogeneous equilibria: a racemic compound (a 1:1 stoichiometric compound), a
conglomerate (a physical mixture of particles with opposite chirality) or, more
rarely, as a solid solution (a crystalline architecture exhibiting a lack of
chiral discrimination with respect to the two enantiomers). Due to the scarce
occurrence of solid solutions, only a few examples of such behavior are known,
and even fewer systems have been investigated by means of single crystal X-ray
diffraction. Yet, preliminary work performed in the 1970s by several research
teams revealed that structural investigations of solid solutions could provide
valuable insights into chiral discrimination mechanisms at the crystal lattice
scale. In the present paper, our aim is to review published cases of enantiomeric
solid solutions for which both melting phase diagrams and crystal structures are
available in order to analyze the lack of chiral discrimination associated to
these phases. Our methodology consists in considering both the molecular and
crystallographic aspects of stereoselectivity with the final aim of identifying
structural criteria responsible for the occurrence of solid solutions. The
experimental conditions allowing access to solid solutions will also be
considered in light of these structural criteria.
PMID- 27510487
TI - Polyphenol-Related Epigenetic Modifications in Osteoarthritis: Current
Therapeutic Perspectives.
AB - The hyaline cartilage is an avascular, aneural and alymphatic tissue with a
limited ability to repair itself. When the cartilage is exposed to some kind of
injury, it usually triggers osteoarthritis (OA), a prevalent and degenerative
joint disease closely related to aging. OA is both complex and multifactorial,
and is the most common form of arthritis, being positioned as a major cause of
pain and dysfunction in the world. In addition, high OA prevalence can greatly
affect work capacity, making this disease a significant social problem,
therefore, its prevention and treatment becomes a priority. At this time, there
are numerous therapeutic strategies available to improve hyaline cartilage repair
by using chondrocytes or mesenchymal cells, but neither is effective enough to
generate functional and durable tissue reparation over time. In OA, chondrocytes
have an aberrant gene expression and phenotype, resulting in a loss of balance
between anabolic and catabolic processes. Environmental influences such as
radiation, infection, smoking, nutrients, toxins and stress can affect gene
expression patterns, which may constitute risk factors for various chronic and
degenerative diseases, such as OA. In addition, considerable evidence shows that
epigenetic mechanisms play an important role in OA chondrogenesis and
pathogenesis. Natural plant-derived products such as polyphenols, which are
secondary metabolites considered to have potential activity to block inflammation
in several degenerative diseases, can stimulate epigenetic modifications, and may
provide new therapeutic targets and cost-effective treatments. This review aims
to present various polyphenolbased therapies currently used for the treatment of
several progressive diseases, including OA.
PMID- 27510488
TI - Development of Novel miRNA-based Vaccines and Antivirals against Enterovirus 71.
AB - The Hand, Foot and Mouth Disease (HFMD) is caused by Enterovirus 71 (EV-A71) and
Coxsackieviruses. Common HFMD symptoms are high fever (>= 39 degrees C), rashes,
and ulcers but complications due to virulent EV-A71 may arise leading to
cardiopulmonary failure and death. The lack of vaccines and antiviral drugs
against EV-A71 highlights the urgency of developing preventive and treatment
agents. Recent studies have reported the emergence of novel antiviral agents and
vaccines that utilize microRNAs (miRNAs). They belong to a class of small (19-24
nt) non coding RNA molecules. As miRNAs play a major role in the host regulatory
system, there is a huge opportunity for interplay between host miRNAs and EV-A71
expressions. A total of 42 out of 64 miRNAs were up-regulated in EV-A71-infected
cells. There was consistent up-regulation of miR-1246 gene expression that
targeted the DLG3 gene which contributes to neurological pathogenesis. In
contrast, miR-30a that targets calcium channels for membrane transportation was
down-regulated. This leads to repression of EV-A71 replication. The impact of
host miRNAs on immune activation, shutdown of host protein synthesis, apoptosis,
signal transduction and viral replication are discussed. miRNAs have been used in
the construction of live attenuated vaccines (LAV) such as the poliovirus LAV
that has miRNA binding sites for let-7a or miR-124a. The miRNAbearing vaccine
will not replicate in neuronal cells carrying the corresponding miRNA but could
still replicate in the gastrointestinal tract and hence remains to act as
immunogens. As such, miRNAs are attractive candidates to be developed as vaccines
and antivirals.
PMID- 27510489
TI - Enkephalin-Fentanyl Multifunctional Opioids as Potential Neuroprotectants for
Ischemic Stroke Treatment.
AB - BACKGROUND: Ischemic stroke is one of the leading causes of mortality and
morbidity in the world and effective neuroprotectants are yet to be developed.
Recent studies have demonstrated excellent neuroprotective effects of a bivalent
enkephalin opioid agonist, biphalin in multiple stroke models. METHODS: The
purpose of this study is to evaluate novel multifunctional enkephalin-fentanyl
opioid agonists, LYS436, LYS739 and LYS416 for their neuroprotective potential
using in vitro and in vivo ischemic stroke models and to compare the effect to
that of biphalin. RESULTS: In general, all non-selective opioid agonists
significantly decreased neuronal cell death and levels of reactive oxygen species
in primary neurons subjescted to hypoxia-aglycemia/re-oxygenation or NMDA
neurotoxicity. Fluorinated enkephalin-fentanyl conjugate, LYS739 showed enhanced
neuroprotection in both in vitro models compared to biphalin. Based on further in
vitro screening and comparative studies to biphalin, LYS739 was selected as a
lead for in vivo experimentation. A mouse middle cerebral artery occlusion (MCAO)
stroke model was utilized to study biphalin and the lead analog, LYS739. Both
agonists significantly decreased brain infarct and edema ratios compared to
saline treated group. Neurological impairment after stroke was statistically
significantly improved in terms of neurological score and locomotor activities
with LYS739 and biphalin treatment. Importantly, LYS739 and biphalin demonstrated
better neuroprotection compared to fentanyl, and this effect was reversed by non
selective opioid antagonist naltrexone. CONCLUSION: In summary, the results of
this study suggest that the multifunctional fluorinated enkephalin analog, LYS739
can be considered as a potential lead for ischemic stroke research and may
provide advantages given the multimeric peptide-opiate structure.
PMID- 27510490
TI - Antiepileptic Drugs Based on the alpha-Substituted Amide Group Pharmacophore:
From Chemical Crystallography to Molecular Pharmaceutics.
AB - The antiepileptic activity of alpha-substituted acetamides, lactams, and cyclic
imides has been known for over six decades. We recently proposed an alpha
substituted amide group as the minimum pharmacophore responsible for inhibition
of neuronal nicotinic acetylcholine receptors by these compounds, with the
implication that inhibition of these receptors in the brain might be the unifying
mechanism of action for these classes of antiepileptic drugs. In order to realize
the pharmacological potential of these orally administered drugs, the relevant
aspects of solid-state chemistry and pharmaceutics (including solubility and
stability) need to be addressed. A better - more cohesive and generalized -
understanding of the solid-state properties of these drugs would pave the road
for a rational approach to their development, formulation, and manufacturing. In
this paper, Pharmaceutically relevant aspects of the crystal structure and solid
state chemistry of antiepileptic drugs containing the alpha-substituted amide
bond pharmacophore - alpha-substituted acetamides, lactams, and cyclic imides and
the structurally related barbiturates, hydantoins, and acetylureas are reviewed.
The applicable experimental and computational approaches are also briefly
mentioned.
PMID- 27510491
TI - Metabolic Features Across the Female Life Span in Women with PCOS.
AB - Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine metabolic
disorder and is presently considered a family pathology. It is associated with
obesity, insulin resistance and metabolic syndrome. Racial, ethnic and
environmental factors may be important in determining the clinical manifestations
of this syndrome. Polycystic ovary syndrome is an exclusion diagnosis and,
therefore, should be distinguished from the physiological changes typical for the
age and from other hyperandrogenic disorders. Early diagnosis is important since
this syndrome is associated with reproductive, oncologic and metabolic risks.
Interestingly, the clinical features of this disorder may change throughout the
lifespan of a PCOS woman, starting from adolescence to postmenopausal age. During
the first decades of life the main features are in the reproductive area, while
later in life metabolic abnormalities are more evident. While the assessment of
insulin resistance is not part of the diagnosis of PCOS, it has been demonstrated
that this metabolic component appears early in life and persists over time.
Moreover during puberty and pregnancy, insulin resistance is exacerbated.
Pregnancy represents an important stage, as the offspring of these patients may
be reprogrammed and inherit some of the metabolic and reproductive features of
their mothers. In the present review, we will focus on several metabolic aspects
of the PCOS condition at different stages of life in a Chilean population.
PMID- 27510493
TI - RNAi-Based Therapy in Experimental Ischemia-Reperfusion Injury. The New Targets.
AB - BACKGROUND: Ischemia reperfusion injury is an important pathophysiological
process in many fields such as transplantation, stroke, atherosclerosis, trauma
and myocardial infarction. Recent advances in gene silencing may help to reduce
ischemic effects, targeting molecules related to this pathological process.
METHODS AND RESULTS: Here, we review the different silencing approaches in
ischemic injury, highlighting the role of co-stimulatory molecules in renal
transplantation. CONCLUSION: Gene silencing appears as a new strategy to prevent
the inflammation and injury associated with ischemia.
PMID- 27510492
TI - Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome:
Dopaminergic Key to Homeostasis and Neuroplasticity.
AB - Willuhn et al., observed that habitual cocaine use was correlated with reductions
in D2/D3 receptors linked to decreased cue activation in occipital cortex and
cerebellum. Dopamine agonist therapy maintains dopamine function and is a relapse
prevention tactic focused on psychoactive drug and behavioral addictions.
Medication Assisted Treatment (MAT) with emphasis on glutaminergic medications
fails in the long-term treatment of Reward Deficiency Syndrome Behaviors (RDS).
While the careful use of "dopamine antagonist-therapy" short-term is supported,
the research-based concept of "dopamine agonist therapy" in long-term is
proposed. Neurogenetics and epigenetics are important in understanding treatment
response and clinical outcomes. The neuro-mechanisms involving "dopamine
homeostasis" are key to understanding recovery from drug and non-drug addictive
behaviors. For example, patients who carry the DRD2 A1 allele (30-40 less D2
receptors) should consider Neuronutriant-Amino-Acid therapy (KB220 variants) a
prevention modality. DRD2 A1 allele carriers show amplified striatal function of
L-amino acid decarboxylase, prior to dopamine biosynthesis. Another example is
the effect of Acute Tyrosine Phenylalanine Depletion (ATPD) on decision-making
and reward found carriers with amino-acid deficiency (ATPD). They experienced
attenuated reward and reduced decision-making ability as quantified by Iowa
Gambling Task (IGT). Future research should be directed at asking the question;
Would "dopamine agonist therapy" using KB220 variants reduce methylation and
increase acetyl groups to enhance DRD2 expression especially in DRD2 A1 allele
carriers and lead to increased dopamine function and a reduction of drug and non
drug seeking behaviors?
PMID- 27510494
TI - The role of the dorsolateral prefrontal cortex in early threat processing: a TMS
study.
AB - Previous studies demonstrated that excitatory (high frequency) offline
transcranial magnetic stimulation (TMS) over the left and right dorsolateral
prefrontal cortex (DLPFC) modulates attention allocation on threatening stimuli
in non-clinical samples. These studies only employed offline TMS protocol that
did not allow investigating the effect of the stimulation on the early stage of
threat processing. In this study, the role of the right and left dorsolateral
prefrontal cortex in early threat processing was investigated in high and low
anxious individuals by means of an inhibitory single-pulse online TMS protocol.
Our results demonstrated the role of the left DLPFC in an early stage of threat
processing and that this effect is modulated by individuals' anxiety level. The
inhibitory stimulation of the left DLPFC determined a disengagement bias in high
anxious individuals, while the same stimulation determined an attentional
avoidance in low anxious individuals. The findings of the present study suggest
that right and left DLPFC are differently involved in early threat processing of
healthy individuals.
PMID- 27510495
TI - Intrinsic functional connectivity underlying successful emotion regulation of
angry faces.
AB - Most of our social interaction is naturally based on emotional information
derived from the perception of faces of other people. Negative facial expressions
of a counterpart might trigger negative emotions and initiate emotion regulatory
efforts to reduce the impact of the received emotional message in a perceiver.
Despite the high adaptive value of emotion regulation in social interaction, the
neural underpinnings of it are largely unknown. To remedy this, this study
investigated individual differences in emotion regulation effectiveness during
the reappraisal of angry faces on the underlying functional activity using
functional magnetic resonance imaging (fMRI) as well as the underlying functional
connectivity using resting-state fMRI. Greater emotion regulation ability was
associated with greater functional activity in the ventromedial prefrontal
cortex. Furthermore, greater functional coupling between activity in the
ventrolateral prefrontal cortex and the amygdala was associated with emotion
regulation success. Our findings provide a first link between prefrontal
cognitive control and subcortical emotion processing systems during successful
emotion regulation in an explicitly social context.
PMID- 27510496
TI - Brain potentials predict learning, transmission and modification of an artificial
symbolic system.
AB - It has recently been argued that symbolic systems evolve while they are being
transmitted across generations of learners, gradually adapting to the relevant
brain structures and processes. In the context of this hypothesis, little is
known on whether individual differences in neural processing capacity account for
aspects of 'variation' observed in symbolic behavior and symbolic systems. We
addressed this issue in the domain of auditory processing. We conducted a
combined behavioral and EEG study on 2 successive days. On day 1, participants
listened to standard and deviant five-tone sequences: as in previous oddball
studies, an mismatch negativity (MMN) was elicited by deviant tones. On day 2,
participants learned an artificial signaling system from a trained confederate of
the experimenters in a coordination game in which five-tone sequences were
associated to affective meanings (emotion-laden pictures of human faces). In a
subsequent game with identical structure, participants transmitted and
occasionally changed the signaling system learned during the first game. The MMN
latency from day 1 predicted learning, transmission and structural modification
of signaling systems on day 2. Our study introduces neurophysiological methods
into research on cultural transmission and evolution, and relates aspects of
variation in symbolic systems to individual differences in neural information
processing.
PMID- 27510497
TI - The role of the orbitofrontal cortex in regulation of interpersonal space:
evidence from frontal lesion and frontotemporal dementia patients.
AB - Interpersonal distance is central to communication and complex social behaviors
but the neural correlates of interpersonal distance preferences are not defined.
Previous studies suggest that damage to the orbitofrontal cortex (OFC) is
associated with impaired interpersonal behavior. To examine whether the OFC is
critical for maintaining appropriate interpersonal distance, we tested two groups
of patients with OFC damage: Patients with OFC lesions and patients with
behavioral variant frontotemporal dementia. These two groups were compared to
healthy controls and to patients with lesions restricted to the dorsolateral
prefrontal cortex. Only patients with OFC damage showed abnormal interpersonal
distance preferences, which were significantly different from both controls and
patients with dorsolateral prefrontal damage. The comfortable distances these
patients chose with strangers were significantly closer than the other groups and
resembled distances normally used with close others. These results shed light on
the role of the OFC in regulating social behavior and may serve as a simple
diagnostic tool for dementia or lesion patients.
PMID- 27510498
TI - Oxytocin enhances inter-brain synchrony during social coordination in male
adults.
AB - Recent brain imaging research has revealed oxytocin (OT) effects on an
individual's brain activity during social interaction but tells little about
whether and how OT modulates the coherence of inter-brain activity related to two
individuals' coordination behavior. We developed a new real-time coordination
game that required two individuals of a dyad to synchronize with a partner
(coordination task) or with a computer (control task) by counting in mind
rhythmically. Electroencephalography (EEG) was recorded simultaneously from a
dyad to examine OT effects on inter-brain synchrony of neural activity during
interpersonal coordination. Experiment 1 found that dyads showed smaller
interpersonal time lags of counting and greater inter-brain synchrony of alpha
band neural oscillations during the coordination (vs control) task and these
effects were reliably observed in female but not male dyads. Moreover, the
increased alpha-band inter-brain synchrony predicted better interpersonal
behavioral synchrony across all participants. Experiment 2, using a double blind,
placebo-controlled between-subjects design, revealed that intranasal OT vs
placebo administration in male dyads improved interpersonal behavioral synchrony
in both the coordination and control tasks but specifically enhanced alpha-band
inter-brain neural oscillations during the coordination task. Our findings
provide first evidence that OT enhances inter-brain synchrony in male adults to
facilitate social coordination.
PMID- 27510500
TI - Highly Boosted Oxygen Reduction Reaction Activity by Tuning the Underwater
Wetting State of the Superhydrophobic Electrode.
AB - By rationally designing superhydrophobic electrodes with different underwater
wetting states, it is revealed that only the underwater Wenzel-Cassie coexistent
state shows the clearly enhanced ability in catalyzing the oxygen reduction
reaction, a typical underwater gas-consuming reaction at electrode. It is
proposed that the maximizing and stabilizing the liquid/gas/solid triphase
interface, endowed by the underwater Wenzel-Cassie coexistent state, plays a
rather crucial role.
PMID- 27510499
TI - Amygdala selectively modulates defensive responses evoked from the superior
colliculus in non-human primates.
AB - Brain circuitry underlying defensive behaviors includes forebrain modulatory
sites, e.g. the amygdala and hypothalamus, and midbrain effector regions, such as
the deep/intermediate layers of the superior colliculus (DLSC). When
disinhibited, this network biases behavior towards reflexive defense reactions.
While well characterized in rodent models, little is known about this system in
the primate brain. Employing focal pharmacological manipulations, we have
previously shown that activation of the DLSC triggers reflexive defensive
responses, including cowering, escape behaviors and defensive vocalizations.
Here, we show that activation of the DLSC also disrupts normal dyadic social
interactions between familiar pairs of monkeys. When the basolateral complex of
the amygdala (BLA) was inhibited concurrent with DLSC activation, cowering
behavior was attenuated, whereas escape behaviors and defensive vocalizations
were not. Moreover, inhibition of the BLA, previously shown to produce a profound
increase in dyadic social interactions, was unable to normalize the decrease in
social behavior resulting from DLSC activation. Together these data provide an
understanding of forebrain-midbrain interactions in a species and circuit with
translational relevance for the psychiatry of anxiety and post-traumatic stress
disorders.
PMID- 27510501
TI - Design of a Yellow-Emitting Phosphor with Enhanced Red Emission via Valence State
control for Warm White LEDs Application.
AB - The phosphor-converted warm W-LED have being rapidly developed due to the
stringent requirements of general illumination. Here, we utilized a strategy to
synergistically enhance the red region and emission intensity of novel Eu
activated yellow-emitting LaSiO2N phosphors. This was realized by predicting
optimum crystal structure, and governing the concentration of doping ions as well
as preparation temperature. By using these straight-forward methods, we were able
to vary the valence to enhance the red region and improve the quantum efficiency
of LaSiO2N phosphor. The warm W-LED lamp fabricated with this red region enhanced
LaSiO2N:Eu phosphor exhibited high CRI (Ra = 86), suitable CCT (5783 K) and CIE
chromaticity (0.33, 0.36), indicating this synergistically enhanced strategy
could be used for design of yellow-emitting phosphor materials to obtain warm W
LEDs.
PMID- 27510502
TI - The title and data of Robinson and Madison (2016) are valid.
PMID- 27510503
TI - Fosaprepitant Dimeglumine: A Review in the Prevention of Nausea and Vomiting
Associated with Chemotherapy.
AB - Intravenous fosaprepitant dimeglumine (Emend((r)) for injection, IVEmend((r));
henceforth referred to as fosaprepitant) is a prodrug of and is rapidly converted
to the antiemetic aprepitant, and is approved in several countries worldwide (as
part of an antiemetic regimen) for the prevention of nausea and vomiting
associated with highly and moderately emetogenic chemotherapy (HEC and MEC). This
narrative review discusses the pharmacological properties of intravenous
fosaprepitant and its clinical efficacy and tolerability in the prevention of
nausea and vomiting associated with HEC and MEC. In large, randomized phase III
clinical trials, a single intravenous dose of fosaprepitant 150 mg was an
effective and generally well tolerated addition to an antiemetic regimen that
included dexamethasone and a serotonin 5-HT3 receptor antagonist in adult cancer
patients undergoing treatment with HEC or MEC. It was also noninferior to an oral
aprepitant-based regimen in adult cancer patients undergoing HEC treatment. The
tolerability profile of a fosaprepitant-based regimen was typical of that in
patients receiving emetogenic chemotherapy, and adverse events were generally
consistent with those observed with an aprepitant-based regimen. Fosaprepitant
provides a useful addition to antiemetic therapy regimens.
PMID- 27510504
TI - Higher Vulnerability of Menadione-Exposed Cortical Astrocytes of Glutaryl-CoA
Dehydrogenase Deficient Mice to Oxidative Stress, Mitochondrial Dysfunction, and
Cell Death: Implications for the Neurodegeneration in Glutaric Aciduria Type I.
AB - Patients affected by glutaric aciduria type I (GA-I) show progressive cortical
leukoencephalopathy whose pathogenesis is poorly known. In the present work, we
exposed cortical astrocytes of wild-type (Gcdh +/+ ) and glutaryl-CoA
dehydrogenase knockout (Gcdh -/- ) mice to the oxidative stress inducer menadione
and measured mitochondrial bioenergetics, redox homeostasis, and cell viability.
Mitochondrial function (MTT and JC1-mitochondrial membrane potential assays),
redox homeostasis (DCFH oxidation, nitrate and nitrite production, GSH
concentrations and activities of the antioxidant enzymes SOD and GPx), and cell
death (propidium iodide incorporation) were evaluated in primary cortical
astrocyte cultures of Gcdh +/+ and Gcdh -/- mice unstimulated and stimulated by
menadione. We also measured the pro-inflammatory response (TNFalpha levels, IL1
beta and NF-kB) in unstimulated astrocytes obtained from these mice. Gcdh -/-
mice astrocytes were more vulnerable to menadione-induced oxidative stress
(decreased GSH concentrations and altered activities of the antioxidant enzymes),
mitochondrial dysfunction (decrease of MTT reduction and JC1 values), and cell
death as compared with Gcdh +/+ astrocytes. A higher inflammatory response
(TNFalpha, IL1-beta and NF-kB) was also observed in Gcdh -/- mice astrocytes.
These data indicate a higher susceptibility of Gcdh -/- cortical astrocytes to
oxidative stress and mitochondrial dysfunction, probably leading to cell death.
It is presumed that these pathomechanisms may contribute to the cortical
leukodystrophy observed in GA-I patients.
PMID- 27510506
TI - The Interaction of TXNIP and AFq1 Genes Increases the Susceptibility of
Schizophrenia.
AB - Although previous studies showed the reduced risk of cancer in patients with
schizophrenia, whether patients with schizophrenia possess genetic factors that
also contribute to tumor suppressor is still unknown. In the present study, based
on our previous microarray data, we focused on the tumor suppressor genes TXNIP
and AF1q, which differentially expressed in patients with schizophrenia. A total
of 413 patients and 578 healthy controls were recruited. We found no significant
differences in genotype, allele, or haplotype frequencies at the selected five
single nucleotide polymorphisms (SNPs) (rs2236566 and rs7211 in TXNIP gene;
rs10749659, rs2140709, and rs3738481 in AF1q gene) between patients with
schizophrenia and controls. However, we found the association between the
interaction of TXNIP and AF1q with schizophrenia by using the MDR method followed
by traditional statistical analysis. The best gene-gene interaction model
identified was a three-locus model TXNIP (rs2236566, rs7211)-AF1q (rs2140709).
After traditional statistical analysis, we found the high-risk genotype
combination was rs2236566 (GG)-rs7211(CC)-rs2140709(CC) (OR = 1.35 [1.03-1.76]).
The low-risk genotype combination was rs2236566 (GT)-rs7211(CC)-rs2140709(CC) (OR
= 0.67 [0.49-0.91]). Our finding suggested statistically significant role of
interaction of TXNIP and AF1q polymorphisms (TXNIP-rs2236566, TXNIP-rs7211, and
AF1q-rs2769605) in schizophrenia susceptibility.
PMID- 27510505
TI - The Neurobiology of Depression: an Integrated Overview from Biological Theories
to Clinical Evidence.
AB - Depressive disorders are heterogeneous diseases, and the complexity of symptoms
has led to the formulation of several aethiopathological hypotheses. This
heterogeneity may account for the following open issues about antidepressant
therapy: (i) antidepressants show a time lag between pharmacological effects,
within hours from acute drug administration, and therapeutic effects, within two
four weeks of subchronic treatment; (ii) this latency interval is critical for
the patient because of the possible further mood worsening that may result in
suicide attempts for the seemingly ineffective therapy and for the apparent
adverse effects; (iii) and only 60-70 % of treated patients successfully respond
to therapy. In this review, the complexity of the biological theories that try to
explain the molecular mechanisms of these diseases is considered, encompassing
(i) the classic "monoaminergic hypothesis" alongside the updated hypothesis
according to which long-term therapeutical action of antidepressants is mediated
by intracellular signal transduction pathways and (ii) the hypothalamic-pituitary
adrenal axis involvement. Although these models have guided research efforts in
the field for decades, they have not generated a compelling and conclusive model
either for depression pathophysiology or for antidepressant drugs' action. So,
other emerging theories are discussed: (iii) the alterations of neuroplasticity
and neurotrophins in selective vulnerable cerebral areas; (iv) the involvement of
inflammatory processes; (v) and the alterations in mitochondrial function and
neuronal bioenergetics. The focus is put on the molecular and theoretical links
between all these hypotheses, which are not mutually exclusive but otherwise
tightly correlated, giving an integrated and comprehensive overview of the
neurobiology of depressive disorders.
PMID- 27510508
TI - Experience of nursing support from the perspective of patients with cancer in
mainland China.
AB - This study was conducted to understand patients' experiences of nursing support,
to identify gaps between patients' expected needs and the nursing support they
received, and to explore reasons for such disparity. A qualitative study with a
phenomenological approach was used. A purposive sample of 22 patients with
different types of cancer was recruited and interviewed using semistructured
guidelines. The data were analyzed using phenomenological analytic methods.
Several needs regarding nursing support were expressed, including informational,
psychological, clinical, care coordination and communication needs, and there
were some unmet or partially-met needs. Reasons for the disparities covered both
patient- and nurse-related factors, including patients' lack of awareness
regarding how to acquire professional assistance and reluctance to express their
needs, and nurses' lack of active communication with patients, inability to
provide specific support, and limited resources for coordination. The
expectations of nursing support did not always correspond with the actual
delivery of nursing care. A tailored intervention is warranted to meet patients'
expectations, which might contribute to quality-of-care improvements.
PMID- 27510507
TI - Advanced Imaging in Osteoarthritis.
AB - CONTEXT: Radiography is widely accepted as the gold standard for diagnosing
osteoarthritis (OA), but it has limitations when assessing early stage OA and
monitoring progression. While there are improvements in the treatment of OA, the
challenge is early recognition. EVIDENCE ACQUISITION: MEDLINE and PubMed as well
as professional orthopaedic and imaging websites were reviewed from 2006 to 2016.
STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Magnetic
resonance imaging (MRI) can provide the most comprehensive assessment of joint
injury and OA with the advantages of being noninvasive and multiplanar with
excellent soft tissue contrast. However, MRI is expensive, time consuming, and
not widely used for monitoring OA clinically. Computed tomography (CT) and CT
arthrography (CTA) can also be used to evaluate OA, but these are also invasive
and require radiation exposure. Ultrasound is particularly useful for evaluation
of synovitis but not for progression of OA. CONCLUSION: MRI, CT, and CTA are
available for the diagnosis and monitoring of OA. Improvement in techniques and
decrease in cost can allow some of these modalities to be effective methods of
detecting early OA.
PMID- 27510509
TI - Mercury Methylation by Cobalt Corrinoids: Relativistic Effects Dictate the
Reaction Mechanism.
AB - The methylation of Hg(II) (SCH3 )2 by corrinoid-based methyl donors proceeds in a
concerted manner through a single transition state by transfer of a methyl
radical, in contrast to previously proposed reaction mechanisms. This reaction
mechanism is a consequence of relativistic effects that lower the energies of the
mercury 6p1/2 and 6p3/2 orbitals, making them energetically accessible for
chemical bonding. In the absence of spin-orbit coupling, the predicted reaction
mechanism is qualitatively different. This is the first example of relativity
being decisive for the nature of an observed enzymatic reaction mechanism.
PMID- 27510510
TI - A Comparative Analysis of Sonic Defences in Bombycoidea Caterpillars.
AB - Caterpillars have long been used as models for studying animal defence. Their
impressive armour, including flamboyant warning colours, poisonous spines,
irritating sprays, and mimicry of plant parts, snakes and bird droppings, has
been extensively documented. But research has mainly focused on visual and
chemical displays. Here we show that some caterpillars also exhibit sonic
displays. During simulated attacks, 45% of 38 genera and 33% of 61 species of
silk and hawkmoth caterpillars (Bombycoidea) produced sounds. Sonic caterpillars
are found in many distantly-related groups of Bombycoidea, and have evolved four
distinct sound types- clicks, chirps, whistles and vocalizations. We propose that
different sounds convey different messages, with some designed to warn of a
chemical defence and others, to startle predators. This research underscores the
importance of exploring acoustic communication in juvenile insects, and provides
a model system to explore how different signals have evolved to frighten, warn or
even trick predators.
PMID- 27510512
TI - Cyclization of N-arylcyclopropanecarboxamides into N-arylpyrrolidin-2-ones under
electron ionization and in the condensed phase.
AB - RATIONALE: Mass spectrometry is known as an excellent method to predict the
behavior of organic compounds in solution. The behavior of organic compounds in
the gas phase inside the ion source of a mass spectrometer allows their intrinsic
properties to be defined, avoiding the influence of intermolecular interactions,
counter ions and solvent effects. METHODS: Arylpyrrolidin-2-ones were obtained by
condensed-phase synthesis from the corresponding N-arylcyclopropanecarboxamides.
Electron ionization (EI) with accurate mass measurements by high-resolution time
of-flight mass-spectrometry and quantum chemical calculations were used to
understand the behavior of the molecular radical cations of N
arylcyclopropanecarboxamides and N-arylpyrrolidin-2-ones in the ion source of a
mass spectrometer. The geometries of the molecules, transition states, and
intermediates were fully optimized using DFT-PBE calculations. RESULTS:
Fragmentation schemes, ion structures, and possible mechanisms of primary
isomerisation were proposed for isomeric N-arylcyclopropanecarboxamides and N
arylpyrrolidin-2-ones. Based on the fragmentation pattern of the N
arylcyclopropanecarboxamides, isomerisation of the original M+* ions into the M+*
ions of the N-arylpyrrolidin-2-ones was shown to be only a minor process. In
contrast, this cyclization proceeds easily in the condensed phase in the presence
of Bronsted acids. CONCLUSIONS: Based on the experimental data and quantum
chemical calculations the principal mechanism of decomposition of the molecular
ions of N-arylcyclopropanecarboxamides involves their direct fragmentation
without any rearrangements. An alternative mechanism is responsible for the
isomerisation of a small portion of the higher energy molecular ions into the
corresponding N-arylpyrrolidin-2-one ions. Copyright (c) 2016 John Wiley & Sons,
Ltd.
PMID- 27510513
TI - Engineered T Cells Improve Pancreatic Cancer Outcomes in Mice.
PMID- 27510514
TI - "P < 0.05" Might Not Mean What You Think: American Statistical Association
Clarifies P Values.
PMID- 27510511
TI - Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic
heart disease, and ischemic stroke events: systematic review and dose-response
meta-analysis for the Global Burden of Disease Study 2013.
AB - OBJECTIVE: To quantify the dose-response associations between total physical
activity and risk of breast cancer, colon cancer, diabetes, ischemic heart
disease, and ischemic stroke events. DESIGN: Systematic review and Bayesian dose
response meta-analysis. DATA SOURCES: PubMed and Embase from 1980 to 27 February
2016, and references from relevant systematic reviews. Data from the Study on
Global AGEing and Adult Health conducted in China, Ghana, India, Mexico, Russia,
and South Africa from 2007 to 2010 and the US National Health and Nutrition
Examination Surveys from 1999 to 2011 were used to map domain specific physical
activity (reported in included studies) to total activity. ELIGIBILITY CRITERIA
FOR SELECTING STUDIES: Prospective cohort studies examining the associations
between physical activity (any domain) and at least one of the five diseases
studied. RESULTS: 174 articles were identified: 35 for breast cancer, 19 for
colon cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic
stroke (some articles included multiple outcomes). Although higher levels of
total physical activity were significantly associated with lower risk for all
outcomes, major gains occurred at lower levels of activity (up to 3000-4000
metabolic equivalent (MET) minutes/week). For example, individuals with a total
activity level of 600 MET minutes/week (the minimum recommended level) had a 2%
lower risk of diabetes compared with those reporting no physical activity. An
increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%.
The same amount of increase yielded much smaller returns at higher levels of
activity: an increase of total activity from 9000 to 12 000 MET minutes/week
reduced the risk of diabetes by only 0.6%. Compared with insufficiently active
individuals (total activity <600 MET minutes/week), the risk reduction for those
in the highly active category (>=8000 MET minutes/week) was 14% (relative risk
0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789,
0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25%
(0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to
0.811) for ischemic stroke. CONCLUSIONS: People who achieve total physical
activity levels several times higher than the current recommended minimum level
have a significant reduction in the risk of the five diseases studied. More
studies with detailed quantification of total physical activity will help to find
more precise relative risk estimates for different levels of activity.
PMID- 27510515
TI - Physical Activity Associated With Fewer Cancers.
PMID- 27510517
TI - Mammaprint Reveals Who Can Skip Chemotherapy for Breast Cancer.
PMID- 27510518
TI - Tackling Mesothelioma With Immunotherapies.
PMID- 27510520
TI - Accuracy of classification of invasive lobular carcinoma on needle core biopsy of
the breast.
AB - Although the UK National Institute for Health and Care Excellence guidelines
recommend that in patients with biopsy-proven invasive lobular carcinoma (ILC),
preoperative MRI scan is considered, the accuracy of diagnosis of ILC in core
biopsy of the breast has not been previously investigated. Eleven pathology
laboratories from the UK and Ireland submitted data on 1112 cases interpreted as
showing features of ILC, or mixed ILC and IDC/no special type (NST)/other tumour
type, on needle core biopsy through retrieval of histology reports. Of the total
1112 cases, 844 were shown to be pure ILC on surgical excision, 154 were mixed
ILC plus another type (invariably ductal/NST) and 113 were shown to be
ductal/NST. Of those lesions categorised as pure ILC on core, 93% had an element
of ILC correctly identified in the core biopsy sample and could be considered
concordant. Of cores diagnosed as mixed ILC plus another type on core, complete
agreement between core and excision was 46%, with 27% cases of pure ILC, whilst
26% non-concordant. These data indicate that there is not a large excess of
expensive MRIs being performed as a result of miscategorisation histologically.
PMID- 27510521
TI - Voriconazole more likely than posaconazole increases plasma exposure to
sublingual buprenorphine causing a risk of a clinically important interaction.
AB - PURPOSE: This study aimed to determine possible effects of voriconazole and
posaconazole on the pharmacokinetics and pharmacological effects of sublingual
buprenorphine. METHODS: We used a randomized, placebo-controlled crossover study
design with 12 healthy male volunteers. Subjects were given a dose of 0.4 mg (0.6
mg during placebo phase) sublingual buprenorphine after a 5-day oral pretreatment
with either (i) placebo, (ii) voriconazole 400 mg twice daily on the first day
and 200 mg twice daily thereafter or (iii) posaconazole 400 mg twice daily.
Plasma and urine concentrations of buprenorphine and its primary active
metabolite norbuprenorphine were monitored over 18 h and pharmacological effects
were measured. RESULTS: Compared to placebo, voriconazole increased the mean area
under the plasma concentration-time curve (AUC0-infinity) of buprenorphine 1.80
fold (90 % confidence interval 1.45-2.24; P < 0.001), its peak concentration
(Cmax) 1.37-fold (P < 0.013) and half-life (t 1/2 ) 1.37-fold (P < 0.001).
Posaconazole increased the AUC00-infinity of buprenorphine 1.25-fold (P < 0.001).
Most of the plasma norbuprenorphine concentrations were below the limit of
quantification (0.05 ng/ml). Voriconazole, unlike posaconazole, increased the
urinary excretion of norbuprenorphine 1.58-fold (90 % confidence interval 1.18
2.12; P < 0.001) but there was no quantifiable parent buprenorphine in urine.
Plasma buprenorphine concentrations correlated with the pharmacological effects,
but the effects did not differ significantly between the phases. CONCLUSIONS:
Voriconazole, and to a minor extent posaconazole, increase plasma exposure to
sublingual buprenorphine, probably via inhibition of cytochrome P450 3 A and/or P
glycoprotein. Care should be exercised in the combined use of buprenorphine with
triazole antimycotics, particularly with voriconazole, because their interaction
can be of clinical importance.
PMID- 27510522
TI - Traditional Chinese medicine: Pivotal role of the spleen in the metabolism of
aristolochic acid I in rats is dependent on oatp2a1.
AB - The genotoxicity and cytotoxicity of aristolochic acids is well documented, and
the Aristolochiaceae plant family has been widely used in China and India for
medical purposes. However, the mechanisms of aristolochic acid I (AAI) in
treatment and toxicity remain to be fully elucidated. According to the theory of
traditional Chinese medicine (TCM), the spleen is responsible for transportation
and transformation, in which a substance is transformed, absorbed and distributed
in the body. In the present study, rats were randomized into a blank group
without spleen deficiency and a spleen deficiency group to investigate the
metabolism of AAI. The results showed that the concentration of AAI was higher in
the spleen deficiency group, compared with that of the blank group. To further
elucidate this process, the expression of organic anion transporting peptide
(oatp)2a1 in the rats of the two groups were examined following oral
administration of AAI. It was observed that the mRNA level of oatp2a1 in the
small intestine of the blank+AAI 60 min group was downregulated, compared with
that in the blank group. Compared with the mRNA level of oatp2a1 in the spleen
deficiency group, the expression levels in the lung and liver were downregulated
in the spleen deficiency+AAI 5 min group, whereas expression levels in the kidney
in the spleen deficiency+AAI 60 min group were upregulated. Based on the above
results, it was hypothesized that the expression of oatp2a1 may be one of the
mechanisms of AAI metabolism in rats. In TCM, the spleen and certain functions of
the small intestine, are important in AAI metabolism, and affect the toxicity of
AAI. In addition, the lung, liver and kidney may also be involved in spleen
deficiency syndrome in rats.
PMID- 27510523
TI - A blueprint for robotic navigation: pre-clinical simulation for transanal total
mesorectal excision (taTME).
PMID- 27510525
TI - Social networking for patients.
PMID- 27510524
TI - Surgical timing after chemoradiotherapy for rectal cancer, analysis of technique
(STARRCAT): results of a feasibility multi-centre randomized controlled trial.
AB - BACKGROUND: The optimal time of rectal resection after long-course
chemoradiotherapy (CRT) remains unclear. A feasibility study was undertaken for a
multi-centre randomized controlled trial evaluating the impact of the interval
after chemoradiotherapy on the technical complexity of surgery. METHODS: Patients
with rectal cancer were randomized to either a 6- or 12-week interval between CRT
and surgery between June 2012 and May 2014 (ISRCTN registration number:
88843062). For blinded technical complexity assessment, the Observational
Clinical Human Reliability Analysis technique was used to quantify technical
errors enacted within video recordings of operations. Other measured outcomes
included resection completeness, specimen quality, radiological down-staging,
tumour cell density down-staging and surgeon-reported technical complexity.
RESULTS: Thirty-one patients were enrolled: 15 were randomized to 6 and 16-12
weeks across 7 centres. Fewer eligible patients were identified than had been
predicted. Of 23 patients who underwent resection, mean 12.3 errors were observed
per case at 6 weeks vs. 10.7 at 12 weeks (p = 0.401). Other measured outcomes
were similar between groups. CONCLUSIONS: The feasibility of measurement of
operative performance of rectal cancer surgery as an endpoint was confirmed in
this exploratory study. Recruitment of sufficient numbers of patients represented
a challenge, and a proportion of patients did not proceed to resection surgery.
These results suggest that interval after CRT may not substantially impact upon
surgical technical performance.
PMID- 27510526
TI - Metabolites of the PAH diol epoxide pathway and other urinary biomarkers of
phenanthrene and pyrene in workers with and without exposure to bitumen fumes.
AB - PURPOSE: This study investigates the diol epoxide pathway of phenanthrene (PHE)
together with phenolic metabolites of PHE and pyrene (PYR) in workers with and
without exposure to bitumen fumes. METHODS: The metabolite concentrations were
determined in urine samples collected from 91 mastic asphalt workers and 42
construction workers as reference group before and after shift. During shift,
vapours and aerosols of bitumen were measured according to a German protocol in
the workers' breathing zone. RESULTS: The median concentration of vapours and
aerosols of bitumen in mastic asphalt workers was 6.3 mg/m3. Metabolite
concentrations were highest in post-shift urines of smokers with bitumen exposure
and showed an increase during shift. The Spearman correlations between the
creatinine-adjusted concentrations of metabolites and vapours and aerosols of
bitumen in non-smokers were weak (e.g. sum of Di-OH-PYR: 0.28) or negligible
(e.g. 1,2-PHE-diol: 0.08; PHE-tetrol: 0.12). Metabolites from the diol epoxide
pathway of PHE were excreted in higher concentrations than phenolic metabolites
(post-shift, non-smoking asphalt workers: 1,2-PHE-diol 2.59 ug/g crea vs. sum of
all OH-PHE 1.87 ug/g crea). 1,2-PHE-diol was weakly correlated with PHE-tetrol
(Spearman coefficient 0.30), an endpoint of the diol epoxide pathway. By
contrast, we found a close correlation between the sum of 1,6-DiOH-PYR and 1,8
DiOH-PYR with 1-OH-PYR (Spearman coefficient 0.76). CONCLUSIONS: Most urinary PAH
metabolites were higher after shift in bitumen-exposed workers, although the
association with bitumen was weak or negligible likely due to the small PAH
content. The additional metabolites of PHE and PYR complete the picture of the
complex metabolic pathways. Nevertheless, none of the PAH metabolites can be
considered to be a specific biomarker for bitumen exposure.
PMID- 27510527
TI - Ministry-Related Burnout and Stress Coping Mechanisms Among Assemblies of God
Ordained Clergy in Minnesota.
AB - Clergy members suffering from burnout face both personal and professional
complications. This study assessed occupational burnout and stress coping
mechanisms among ministers affiliated with the Assemblies of God, a denomination
that has received little attention in previous burnout-related studies. A cross
sectional design was employed using two instruments with acceptable psychometric
properties. Approximately 65 % of those surveyed were either suffering from
burnout or on the verge of burnout. Statistical differences in coping mechanism
use were found between those who were and were not experiencing some level of
burnout. The results of this study add to the existing understanding of
occupational burnout among clergy members and ways in which burnout may be
alleviated.
PMID- 27510528
TI - Protective Role of Spirituality from the Perspective of Indian College Students
with Suicidal Ideation: "I am here Because God Exists".
AB - Spiritual beliefs are found to be having a significant effect during times of
struggles and trials in peoples' lives. India being a multi-religious society, it
is imperative to establish the relevance of spirituality in the lives of the
college students with suicidal ideation. The current study therefore utilized
focus group methodology to explore the Indian female college students'
perceptions on the protective role of spirituality as a factor contributing to
their positive adaptation in times of adversity. Twenty students participated in
the discussion. The results interestingly surfaced themes supporting the
significance of them on how individuals rely on spiritual beliefs and the
possible implications of the need to address it for positive adaptation. Most of
the participants analogically stated the themes emerged as "something to stay
afloat in the rough sea of life's realities."
PMID- 27510529
TI - The role of microRNA-31 and microRNA-21 as regulatory biomarkers in the
activation of T lymphocytes of Egyptian lupus patients.
AB - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by
familial aggregation and genetic predisposition. MicroRNAs (MiRNAs) serve as
critical biomarkers in lupus patients because of their aberrant expression in
different SLE stages. The study aimed to investigate the correlation of miR-31
and miR-21 with IL-2 in SLE patients as regulatory biomarkers in the activation
of T lymphocytes of Egyptian lupus patients. Quantitative RT-PCR is carried out
to estimate the expressions of miR-31 and miR-21, and IL-2 levels were determined
using ELISA in plasma of 40 patients with SLE, 20 of their first-degree relatives
and 20 healthy controls. The study also determined the systemic lupus
erythematosus disease activity index (SLEDAI) score and proteinuria in SLE
patients. The results revealed that miR-31 was lower expressed, while miR-21 was
high expressed in SLE patients compared to their first-degree relatives and
controls. MiR-31 was negatively correlated with SLEDAI and proteinuria in lupus
patients, while miR-21 showed positive correlation with them. Also we found that
there is a significant positive correlation between miR-31 and IL-2 in SLE
patients, while miR-21 was negatively correlated with IL-2 level in patients. In
conclusion, the study disclosed a significant association between miR-31 and miR
21 expression with IL-2 level in SLE patients. The regulatory biomarkers of miR
31 and miR-21 might have an impact on regulating IL-2 pathway expression and in
turn on the activation of T lymphocytes in SLE.
PMID- 27510530
TI - Macrophage activation syndrome in children with systemic juvenile idiopathic
arthritis and systemic lupus erythematosus.
AB - Macrophage activation syndrome (MAS) is a hyper-inflammatory disorder secondary
to a rheumatic disease such as systemic juvenile idiopathic arthritis (SJIA) and
systemic lupus erythematosus (SLE). We aimed to present the characteristics of
our pediatric MAS patients. Clinical features, laboratory parameters, treatment,
and outcome of 34 patients (28 SJIA; six SLE; 37 MAS episodes) followed at a
tertiary health center between 2009 and 2015 were retrospectively reviewed. The
median age at MAS onset was 11 years. More SJIA patients had MAS at disease onset
than SLE patients (53.6 vs. 16.7 %). Fever, high C-reactive protein and
hyperferritinemia were present in all MAS episodes. Rash was less (p = 0.03), and
fatigue was more frequent (p = 0.042) in SLE than SJIA patients. All received
corticosteroids. Cyclosporine was given in 74.2 % of SJIA-MAS; 66.7 % of SLE-MAS
episodes. Intravenous immunoglobulin, anakinra, or etoposide was administered
during 67.7; 41.9; 32.3 % of SJIA-MAS and 33.3; 33.3; 50 % of SLE-MAS episodes,
respectively. Plasmapheresis was performed during 41.9 % of SJIA-MAS and 33.3 %
of SLE-MAS episodes. The mortality rate was 11.8 % (n = 4;3 SJIA, 1 SLE).
Hepatosplenomegaly was more frequent (p = 0.005), and plasmapheresis was
performed more frequently (p = 0.021) in the patients who died compared to the
cured patients. The median duration between symptom onset and admission to our
hospital was longer among the patients who died (16.5 vs. 7 days; p = 0.049). Our
patients' characteristics were similar to the reported cases, but our mortality
rate is slightly higher probably due to late referral to our center. Early
diagnosis and effective treatment are crucial to prevent mortality.
PMID- 27510532
TI - The effects of resistance exercise and oral nutritional supplementation during
hemodialysis on indicators of nutritional status and quality of life.
AB - BACKGROUND: Protein-energy wasting (PEW) is common in patients undergoing
hemodialysis (HD). Studies have assessed the positive effect of oral nutritional
supplementation (ONS) or resistance exercise (RE) on nutritional status (NS)
markers in patients undergoing HD. METHODS: The aim of this study was to assess
the effect of ONS and RE on NS and the quality of life (QOL) of 36 patients
undergoing HD. In a randomized clinical trial, patients were divided into the
following two groups: a control group (ONS) that received a can of ONS during
their HD sessions and an intervention group (ONS + RE) that received a can of ONS
and underwent a 40-min session of RE during their HD sessions. Both interventions
lasted 12 weeks. The patients' anthropometric, biochemical, dietetic and
bioelectrical impedance measurements as well as their QOL, evaluated using the
Kidney Disease Quality of Life Short Form, were recorded. RESULTS: At baseline,
55.5% of patients presented with PEW according to International Society of Renal
Nutrition and Metabolism criteria (20 patients). We found statistically
significant changes from baseline in both groups, such as increases in body
weight, body mass index, midarm circumference, midarm muscle circumference,
triceps skinfold thickness, fat mass percentage, handgrip strength, phase angle
and serum albumin. A decrease in the prevalence of PEW was observed in both
groups at the end of the intervention. A delta comparison between groups showed
no statistically significant differences in the anthropometric and biochemical
parameters. No significant improvement was observed in QOL and body composition
measured by bioimpedance vector analysis. Dietary energy and protein intake
increased significantly during the study period for all patients. CONCLUSION:
Oral nutritional supplementation during HD improves NS. The addition of RE during
HD does not seem to augment the acute anabolic effects of intradialytic ONS on
NS.
PMID- 27510531
TI - Intracellular calcium increases in vascular smooth muscle cells with progression
of chronic kidney disease in a rat model.
AB - Background: Vascular smooth muscle cells (VSMCs) exhibit phenotypic plasticity,
promoting vascular calcification and increasing cardiovascular risk. Changes in
VSMC intracellular calcium ([Ca 2+ ] i ) are a major determinant of plasticity,
but little is known about changes in [Ca 2+ ] i in chronic kidney disease (CKD).
We have previously demonstrated such plasticity in aortas from our rat model of
CKD and therefore sought to examine changes in [Ca 2+ ] i during CKD progression.
Materials and Methods: We examined freshly isolated VSMCs from aortas of normal
rats, Cy/+ rats (CKD) with early and advanced CKD, and advanced CKD rats treated
without and with 3% calcium gluconate (CKD + Ca 2+ ) to lower parathyroid hormone
(PTH) levels. [Ca 2+ ] i was measured with fura-2. Results: Cy/+ rats developed
progressive CKD, as assessed by plasma levels of blood urea nitrogen, calcium,
phosphorus, parathyroid hormone and fibroblast growth factor 23. VSMCs isolated
from rats with CKD demonstrated biphasic alterations in resting [Ca 2+ ] i :
VSMCs from rats with early CKD exhibited reduced resting [Ca 2+ ] i , while VSMCs
from rats with advanced CKD exhibited elevated resting [Ca 2+ ] i . Caffeine
induced sarcoplasmic reticulum (SR) Ca 2+ store release was modestly increased in
early CKD and was more drastically increased in advanced CKD. The advanced CKD
elevation in SR Ca 2+ store release was associated with a significant increase in
the activity of the sarco-endoplasmic reticulum Ca 2+ ATPase (SERCA); however,
SERCA2a protein expression was decreased in advanced CKD. Following SR Ca 2+
store release, recovery of [Ca 2+ ] i in the presence of caffeine and
extracellular Ca 2+ was attenuated in VSMCs from rats with advanced CKD. This
impairment, together with reductions in expression of the Na + /Ca 2+ exchanger,
suggest a reduction in Ca 2+ extrusion capability. Finally, store-operated Ca 2+
entry (SOCE) was assessed following SR Ca 2+ store depletion. Ca 2+ entry during
recovery from caffeine-induced SR Ca 2+ store release was elevated in advanced
CKD, suggesting a role for exacerbated SOCE with progressing CKD. Conclusions:
With progressive CKD in the Cy/+ rat there is increased resting [Ca 2+ ] i in
VSMCs due, in part, to increased SOCE and impaired calcium extrusion from the
cell. Such changes may predispose VSMCs to phenotypic changes that are a
prerequisite to calcification.
PMID- 27510533
TI - Epicatechin, procyanidins, cocoa, and appetite: a randomized controlled trial.
AB - BACKGROUND: In 2 randomized controlled trials, it was reported that dark
chocolate acutely decreased appetite in human subjects, but the authors did not
assess the types or concentrations of cocoa compounds that are needed. Other
studies have suggested that the cocoa compounds epicatechin and procyanidins may
be involved. OBJECTIVE: We sought to test the hypotheses that, compared with
placebo (an alkalized cocoa mixture containing essentially no epicatechin or
procyanidins), the following beverages cause a decrease in appetite: 1) a
nonalkalized cocoa mixture; 2) epicatechin plus placebo; and 3) procyanidins plus
placebo. We measured the concentrations of cocoa compounds in all beverages.
DESIGN: We used a 4-way randomized, crossover, placebo-controlled trial that was
balanced for period and carryover effects in 28 healthy, young-adult men. We also
conducted a smaller (n = 14), parallel, secondary randomized trial in which we
explored the effects of higher doses of epicatechin and procyanidins. Our primary
measure of appetite was ad libitum pizza intake 150 min after beverage ingestion.
We used a linear mixed-model analysis. RESULTS: Intakes of beverages with the
nonalkalized cocoa mixture that contained 0.6 mg epicatechin, 0.2 mg catechin,
and 2.9 mg monomer-decamer procyanidins/kg body weight did not decrease pizza
intake significantly (P = 0.29) compared with intake of the placebo. In the
smaller secondary trial, a combination of epicatechin and the nonalkalized cocoa
mixture that contained 1.6 mg epicatechin/kg body weight significantly decreased
pizza intake by 18.7% (P = 0.04). CONCLUSIONS: Our nonalkalized cocoa mixture was
associated with an acute decrease in food intake only after being supplemented
with epicatechin. It is possible that epicatechin at a dose of >1.6 mg/kg body
weight, alone or in concert with appropriate catalytic cocoa compounds, may be
useful for helping people control their food intakes. This trial was registered
at clinicaltrials.gov as NCT02408289.
PMID- 27510534
TI - Biofortified beta-carotene rice improves vitamin A intake and reduces the
prevalence of inadequacy among women and young children in a simulated analysis
in Bangladesh, Indonesia, and the Philippines.
AB - BACKGROUND: Vitamin A deficiency continues to be a major public health problem
affecting developing countries where people eat mostly rice as a staple food. In
Asia, rice provides up to 80% of the total daily energy intake. OBJECTIVE: We
used existing data sets from Bangladesh, Indonesia, and the Philippines, where
dietary intakes have been quantified at the individual level to 1) determine the
rice and vitamin A intake in nonpregnant, nonlactating women of reproductive age
and in nonbreastfed children 1-3 y old and 2) simulate the amount of change that
could be achieved in the prevalence of inadequate intake of vitamin A if rice
biofortified with beta-carotene were consumed instead of the rice consumed at
present. DESIGN: We considered a range of 4-20 parts per million (ppm) of beta
carotene content and 10-70% substitution levels for the biofortified rice.
Software was used to estimate usual rice and vitamin A intake for the simulation
analyses. RESULTS: In an analysis by country, the substitution of biofortified
rice for white rice in the optimistic scenario (20 ppm and 70% substitution)
decreased the prevalence of vitamin A inadequacy from baseline 78% in women and
71% in children in Bangladesh. In Indonesia and the Philippines, the prevalence
of inadequacy fell by 55-60% in women and dropped by nearly 30% in children from
baseline. CONCLUSIONS: The results of the simulation analysis were striking in
that even low substitution levels and modest increases in the beta-carotene of
rice produced a meaningful decrease in the prevalence of inadequate intake of
vitamin A. Increasing the substitution levels had a greater impact than
increasing the beta-carotene content by >12 ppm.
PMID- 27510536
TI - Minor degree of hypohydration adversely influences cognition: a mediator
analysis.
AB - BACKGROUND: Because the assumption that small changes in hydration status are
readily compensated by homeostatic mechanisms has been little studied, the
influence of hypohydration on cognition was examined. OBJECTIVES: We assessed
whether a loss of <1% of body mass due to hypohydration adversely influenced
cognition, and examined the possible underlying mechanisms. DESIGN: A total of
101 individuals were subjected to a temperature of 30 degrees C for 4 h and
randomly either did or did not consume 300 mL H2O during that period. Changes in
body mass, urine osmolality, body temperature, and thirst were monitored.
Episodic memory, focused attention, mood, and the perceived difficulty of tasks
were measured on 3 occasions. The data were analyzed with the use of a regression
based approach whereby we looked for variables that mediated the influence of
hypohydration on psychological functioning. RESULTS: Drinking water improved
memory and focused attention. In the short-term, thirst was associated with
poorer memory. Later, a greater loss of body mass was associated with poorer
memory and attention (mean loss: 0.72%). At 90 min, an increase in thirst was
associated with a decline in subjective energy and increased anxiety and
depression, effects that were reduced by drinking water. At 180 min, subjects
found the tests easier if they had consumed water. CONCLUSIONS: Drinking water
was shown, for the first time to our knowledge, to benefit cognitive functioning
when there was a loss of <1% body mass at levels that may occur during everyday
living. Establishing the variables that generate optimal fluid consumption will
help to tailor individual advice, particularly in clinical situations. This trial
was registered at clinicaltrials.gov as NCT02671149.
PMID- 27510535
TI - Predictors of failure of fish-oil therapy for intestinal failure-associated liver
disease in children.
AB - BACKGROUND: Parenteral fish-oil (FO) therapy is a safe and effective treatment
for intestinal failure-associated liver disease (IFALD). Patients whose
cholestasis does not resolve with FO may progress to end-stage liver disease.
OBJECTIVE: We sought to identify factors associated with the failure of FO
therapy in treating IFALD to guide prognostication and referral guidelines.
DESIGN: Prospectively collected data for patients treated with FO at Boston
Children's Hospital from 2004 to 2014 were retrospectively reviewed. Resolution
of cholestasis was defined as sustained direct bilirubin (DB) <2 mg/dL, and
treatment failure as liver transplantation or death while DB was >2 mg/dL as of
July 2015. Demographics, laboratory values, and medical history at FO therapy
initiation were compared between patients who achieved resolution of cholestasis
and those who failed therapy. RESULTS: Among 182 patients treated with FO, 86%
achieved resolution of cholestasis and 14% failed therapy. Patients who failed
therapy had median (IQR) lower birth weight [1020 g (737, 1776 g) compared with
1608 g (815, 2438 g); P = 0.03] and were older at FO initiation [20.4 wk (9.9,
38.6 wk) compared with 11.7 wk (7.3, 21.4 wk); P = 0.02] than patients whose
cholestasis resolved. Patients who failed therapy had more advanced liver disease
at therapy initiation than patients whose cholestasis resolved, as evidenced by
lower median (IQR) gamma-glutamyltransferase [54 U/L (41, 103 U/L) compared with
112 U/L (76, 168 U/L); P < 0.001], higher DB [10.4 mg/dL (7.5, 14.1 mg/dL)
compared with 4.4 mg/dL (3.1, 6.6 mg/dL); P < 0.001], and a higher pediatric end
stage liver disease (PELD) score [22 (14, 25) compared with 12 (7, 15); P <
0.001]. A PELD score of >=15, history of gastrointestinal bleeding, age at FO
initiation >=16 wk, presence of nongastrointestinal comorbidities, and mechanical
ventilation at FO initiation were independent predictors of treatment failure.
CONCLUSIONS: Most infants with IFALD responded to FO therapy with resolution of
cholestasis, and liver transplantation was rarely required. Early FO initiation
once biochemical cholestasis is detected in parenteral nutrition-dependent
patients is recommended. This trial was registered at clinicaltrials.gov as
NCT00910104.
PMID- 27510538
TI - Distinct lipid profiles predict improved glycemic control in obese, nondiabetic
patients after a low-caloric diet intervention: the Diet, Obesity and Genes
randomized trial.
AB - BACKGROUND: An aim of weight loss is to reduce the risk of type 2 diabetes (T2D)
in obese subjects. However, the relation with long-term glycemic improvement
remains unknown. OBJECTIVE: We evaluated the changes in lipid composition during
weight loss and their association with long-term glycemic improvement. DESIGN: We
investigated the plasma lipidome of 383 obese, nondiabetic patients within a
randomized, controlled dietary intervention in 8 European countries at baseline,
after an 8-wk low-caloric diet (LCD) (800-1000 kcal/d), and after 6 mo of weight
maintenance. RESULTS: After weight loss, a lipid signature identified 2 groups of
patients who were comparable at baseline but who differed in their capacities to
lose weight and improve glycemic control. Six months after the LCD, one group had
significant glycemic improvement [homeostasis model assessment of insulin
resistance (HOMA-IR) mean change: -0.92; 95% CI: -1.17, -0.67)]. The other group
showed no improvement in glycemic control (HOMA-IR mean change: -0.26; 95% CI:
0.64, 0.13). These differences were sustained for >=1 y after the LCD. The same
conclusions were obtained with other endpoints (Matsuda index and fasting insulin
and glucose concentrations). Significant differences between the 2 groups were
shown in leptin gene expression in adipose tissue biopsies. Significant
differences were also observed in weight-related endpoints (body mass index,
weight, and fat mass). The lipid signature allowed prediction of which subjects
would be considered to be insulin resistant after 6 mo of weight maintenance
[validation's receiver operating characteristic (ROC) area under the curve (AUC):
71%; 95% CI: 62%, 81%]. This model outperformed a clinical data-only model
(validation's ROC AUC: 61%; 95% CI: 50%, 71%; P = 0.01). CONCLUSIONS: In this
study, we report a lipid signature of LCD success (for weight and glycemic
outcome) in obese, nondiabetic patients. Lipid changes during an 8-wk LCD allowed
us to predict insulin-resistant patients after 6 mo of weight maintenance. The
determination of the lipid composition during an LCD enables the identification
of nonresponders and may help clinicians manage metabolic outcomes with further
intervention, thereby improving the long-term outcome and preventing T2D. This
trial was registered at clinicaltrials.gov as NCT00390637.
PMID- 27510537
TI - Comparing metabolite profiles of habitual diet in serum and urine.
AB - BACKGROUND: Diet plays an important role in chronic disease etiology, but some
diet-disease associations remain inconclusive because of methodologic limitations
in dietary assessment. Metabolomics is a novel method for identifying objective
dietary biomarkers, although it is unclear what dietary information is captured
from metabolites found in serum compared with urine. OBJECTIVE: We compared
metabolite profiles of habitual diet measured from serum with those measured from
urine. DESIGN: We first estimated correlations between consumption of 56 foods,
beverages, and supplements assessed by a food-frequency questionnaire, with 676
serum and 848 urine metabolites identified by untargeted liquid chromatography
mass spectrometry, ultra-high performance liquid chromatography tandem mass
spectrometry, and gas chromatography mass spectrometry in a colon adenoma case
control study (n = 125 cases and 128 controls) while adjusting for age, sex,
smoking, fasting, case-control status, body mass index, physical activity,
education, and caloric intake. We controlled for multiple comparisons with the
use of a false discovery rate of <0.1. Next, we created serum and urine multiple
metabolite models to predict food intake with the use of 10-fold crossvalidation
least absolute shrinkage and selection operator regression for 80% of the data;
predicted values were created in the remaining 20%. Finally, we compared
predicted values with estimates obtained from self-reported intake for
metabolites measured in serum and urine. RESULTS: We identified metabolites
associated with 46 of 56 dietary items; 417 urine and 105 serum metabolites were
correlated with >=1 food, beverage, or supplement. More metabolites in urine (n =
154) than in serum (n = 39) were associated uniquely with one food. We found
previously unreported metabolite associations with leafy green vegetables, sugar
sweetened beverages, citrus, added sugar, red meat, shellfish, desserts, and
wine. Prediction of dietary intake from multiple-metabolite profiles was similar
between biofluids. CONCLUSIONS: Candidate metabolite biomarkers of habitual diet
are identifiable in both serum and urine. Urine samples offer a valid alternative
or complement to serum for metabolite biomarkers of diet in large-scale clinical
or epidemiologic studies.
PMID- 27510539
TI - The effect of the apolipoprotein E genotype on response to personalized dietary
advice intervention: findings from the Food4Me randomized controlled trial.
AB - BACKGROUND: The apolipoprotein E (APOE) risk allele (E4) is associated with
higher total cholesterol (TC), amplified response to saturated fatty acid (SFA)
reduction, and increased cardiovascular disease. Although knowledge of gene risk
may enhance dietary change, it is unclear whether E4 carriers would benefit from
gene-based personalized nutrition (PN). OBJECTIVES: The aims of this study were
to 1) investigate interactions between APOE genotype and habitual dietary fat
intake and modulations of fat intake on metabolic outcomes; 2) determine whether
gene-based PN results in greater dietary change than do standard dietary advice
(level 0) and nongene-based PN (levels 1-2); and 3) assess the impact of
knowledge of APOE risk (risk: E4+, nonrisk: E4-) on dietary change after gene
based PN (level 3). DESIGN: Individuals (n = 1466) recruited into the Food4Me pan
European PN dietary intervention study were randomly assigned to 4 treatment arms
and genotyped for APOE (rs429358 and rs7412). Diet and dried blood spot TC and
omega-3 (n-3) index were determined at baseline and after a 6-mo intervention.
Data were analyzed with the use of adjusted general linear models. RESULTS:
Significantly higher TC concentrations were observed in E4+ participants than in
E4- (P < 0.05). Although there were no significant differences in APOE response
to gene-based PN (E4+ compared with E4-), both groups had a greater reduction in
SFA (percentage of total energy) intake than at level 0 (mean +/- SD: E4+, -0.72%
+/- 0.35% compared with -1.95% +/- 0.45%, P = 0.035; E4-, -0.31% +/- 0.20%
compared with -1.68% +/- 0.35%, P = 0.029). Gene-based PN was associated with a
smaller reduction in SFA intake than in nongene-based PN (level 2) for E4-
participants (-1.68% +/- 0.35% compared with -2.56% +/- 0.27%, P = 0.025).
CONCLUSIONS: The APOE E4 allele was associated with higher TC. Although gene
based PN targeted to APOE was more effective in reducing SFA intake than standard
dietary advice, there was no difference between APOE "risk" and "nonrisk" groups.
Furthermore, disclosure of APOE nonrisk may have weakened dietary response to PN.
This trial was registered at clinicaltrials.gov as NCT01530139.
PMID- 27510542
TI - What Defines Us as Professionals in the Field of Risk Analysis?
AB - In a recent issue of Risk Analysis, the then-President of the Society for Risk
Analysis (SRA), Pamela Williams, has some interesting reflections about the risk
analysis field. She states that the ability and desire to tackle difficult
problems using a risk analytical approach is what uniquely defines us as
professionals in the field of risk analysis. The point of departure for her
discussion is interviews with the plenary speakers of the 2014 SRA Annual
Meeting, who addressed two divisive topics: hydraulic fracking and marijuana use.
She points to several themes that invite contributions from the field of risk
analysis, including: Has the full spectrum of potential risks and benefits been
identified and weighted, and what are the risk tradeoffs or countervailing risks?
Inspired by Williams's reflections, and by analyzing the issues raised in the
interviews, this article seeks to clarify what our field is really providing. A
main conclusion of the article is that it is essential to acknowledge that
professionals in the field of risk analysis merely support the tackling of such
problems, and that their genuine competence-that which distinguishes them from
other professionals-lies in the risk analytical approach itself.
PMID- 27510541
TI - Serum calcium and incident type 2 diabetes: the Atherosclerosis Risk in
Communities (ARIC) study.
AB - BACKGROUND: Elevated serum calcium has been associated with a variety of
metabolic abnormalities and may be associated with a greater risk of diabetes.
OBJECTIVE: The purpose of this study was to test the hypothesis that serum
calcium concentration is positively and independently associated with the
incidence of diabetes and to evaluate the association of calcium-sensing receptor
(CaSR) gene single nucleotide polymorphism (SNP) rs1801725 with incident
diabetes. DESIGN: Atherosclerosis Risk in Communities study participants free of
diabetes at baseline (n = 12,800; mean age: 53.9 y; 22.6% black) were studied for
incident diabetes. Serum calcium was measured at baseline and corrected for serum
albumin. Diabetes was defined by use of glucose concentrations, self-report, or
medication use. Cox proportional hazards regression was used. RESULTS: During a
mean 8.8 y of follow-up, 1516 cases of diabetes were reported. Participants in
the highest compared with lowest calcium quintile were at greater risk of
incident diabetes after adjustment for demographic and lifestyle factors [HR (95%
CI): 1.34 (1.14, 1.57); P-trend across quintiles <0.0001] and with further
adjustment for waist circumference and body mass index [1.26 (1.07, 1.48); P
trend = 0.004]. Additional adjustment for biomarkers on the metabolic pathway
(e.g., 25-hydroxyvitamin D, parathyroid hormone, phosphorus) had little impact.
The calcium-diabetes association was statistically significant in blacks [1.48
(1.11, 1.98); P-trend = 0.002] but not whites [1.17 (0.96, 1.43); P-trend = 0.17]
after adjustment for adiposity. In whites, CaSR gene SNP rs1801725 was associated
with serum calcium but not with risk of diabetes. CONCLUSIONS: Consistent with 3
previous cohort studies, elevated serum calcium was found to be associated with a
greater risk of type 2 diabetes. Further research is needed to understand the
role, if any, that calcium plays in the pathogenesis of diabetes.
PMID- 27510543
TI - Are Pediatric Emergency Physicians More Knowledgeable and Confident to Respond to
a Pediatric Disaster after an Experiential Learning Experience?
AB - OBJECTIVES: Pediatric hospital disaster responders must be well-trained and
prepared to manage children in a mass-casualty incident. Simulations of various
types have been the traditional way of testing hospital disaster plans and
training hospital staff in skills that are used in rare circumstances. The
objective of this longitudinal, survey-based, observational study was to assess
the effect of disaster response and management-based experiential learning on the
knowledge and confidence of advanced learners. METHODS: A simulation-based
workshop was created for practicing Pediatric Emergency Medicine (PEM)
physicians, senior PEM physicians, and critical care and pediatric surgery
residents to learn how to manage a disaster response. Given that this particular
group of learners had never been exposed to such a disaster simulation, its
educational value was assessed with the goal of improving the quality of the
hospital pediatric medical response to a disaster by increasing the responders'
knowledge and confidence. Objective and subjective measures were analyzed using
both a retrospective, pre-post survey, as well as case-based evaluation grids.
RESULTS: The simulation workshop improved the learners' perceived ability to
manage patients in a disaster context and identified strengths and areas needing
improvement for patient care within the disaster context. CONCLUSION: Advanced
learners exposed to an experiential learning activity believed that it improved
their ability to manage patients in a disaster situation and felt that it was
valuable to their learning. Their confidence was preserved six months later. Bank
I , Khalil E . Are pediatric emergency physicians more knowledgeable and
confident to respond to a pediatric disaster after an experiential learning
experience? Prehosp Disaster Med. 2016;31(5):551-556.
PMID- 27510540
TI - Sweet-beverage consumption and risk of pancreatic cancer in the European
Prospective Investigation into Cancer and Nutrition (EPIC).
AB - BACKGROUND: The consumption of sweet beverages has been associated with greater
risk of type 2 diabetes and obesity, which may be involved in the development of
pancreatic cancer. Therefore, it has been hypothesized that sweet beverages may
increase pancreatic cancer risk as well. OBJECTIVE: We examined the association
between sweet-beverage consumption (including total, sugar-sweetened, and
artificially sweetened soft drink and juice and nectar consumption) and
pancreatic cancer risk. DESIGN: The study was conducted within the European
Prospective Investigation into Cancer and Nutrition cohort. A total of 477,199
participants (70.2% women) with a mean age of 51 y at baseline were included, and
865 exocrine pancreatic cancers were diagnosed after a median follow-up of 11.60
y (IQR: 10.10-12.60 y). Sweet-beverage consumption was assessed with the use of
validated dietary questionnaires at baseline. HRs and 95% CIs were obtained with
the use of multivariable Cox regression models that were stratified by age, sex,
and center and adjusted for educational level, physical activity, smoking status,
and alcohol consumption. Associations with total soft-drink consumption were
adjusted for juice and nectar consumption and vice versa. RESULTS: Total soft
drink consumption (HR per 100 g/d: 1.03; 95% CI: 0.99, 1.07), sugar-sweetened
soft-drink consumption (HR per 100 g/d: 1.02; 95% CI: 0.97, 1.08), and
artificially sweetened soft-drink consumption (HR per 100 g/d: 1.04; 95% CI:
0.98, 1.10) were not associated with pancreatic cancer risk. Juice and nectar
consumption was inversely associated with pancreatic cancer risk (HR per 100 g/d:
0.91; 95% CI: 0.84, 0.99); this association remained statistically significant
after adjustment for body size, type 2 diabetes, and energy intake. CONCLUSIONS:
Soft-drink consumption does not seem to be associated with pancreatic cancer
risk. Juice and nectar consumption might be associated with a modest decreased
pancreatic cancer risk. Additional studies with specific information on juice and
nectar subtypes are warranted to clarify these results.
PMID- 27510544
TI - U6atac snRNA stem-loop interacts with U12 p65 RNA binding protein and is
functionally interchangeable with the U12 apical stem-loop III.
AB - Formation of catalytic core of the U12-dependent spliceosome involves U6atac and
U12 interaction with the 5' splice site and branch site regions of a U12
dependent intron, respectively. Beyond the formation of intermolecular helix I
region between U6atac and U12 snRNAs, several other regions within these RNA
molecules are predicted to form stem-loop structures. Our previous work
demonstrated that the 3' stem-loop region of U6atac snRNA contains a U12
dependent spliceosome-specific targeting activity. Here, we show a detailed
structure-function analysis and requirement of a substructure of U6atac 3' stem
loop in U12-dependent in vivo splicing. We show that the C-terminal RNA
recognition motif of p65, a U12 snRNA binding protein, also binds to the distal
3' stem-loop of U6atac. By using a binary splice site mutation suppressor assay
we demonstrate that p65 protein-binding apical stem-loop of U12 snRNA can be
replaced by this U6atac distal 3' stem-loop. Furthermore, we tested the
compatibility of the U6atac 3' end from phylogenetically distant species in a
human U6atac background, to establish the evolutionary relatedness of these
structures and in vivo function. In summary, we demonstrate that RNA-RNA and RNA
protein interactions in the minor spliceosome are highly plastic as compared to
the major spliceosome.
PMID- 27510545
TI - Adaptation to elevated CO2 in different biodiversity contexts.
AB - In the absence of migration, species persistence depends on adaption to a
changing environment, but whether and how adaptation to global change is altered
by community diversity is not understood. Community diversity may prevent,
enhance or alter how species adapt to changing conditions by influencing
population sizes, genetic diversity and/or the fitness landscape experienced by
focal species. We tested the impact of community diversity on adaptation by
performing a reciprocal transplant experiment on grasses that evolved for 14
years under ambient and elevated CO2, in communities of low or high species
richness. Using biomass as a fitness proxy, we find evidence for local adaptation
to elevated CO2, but only for plants assayed in a community of similar diversity
to the one experienced during the period of selection. Our results indicate that
the biological community shapes the very nature of the fitness landscape within
which species evolve in response to elevated CO2.
PMID- 27510547
TI - Public health: What's app in emergency cardiovascular care?
PMID- 27510546
TI - Calculating protein-ligand binding affinities with MMPBSA: Method and error
analysis.
AB - Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) methods have become
widely adopted in estimating protein-ligand binding affinities due to their
efficiency and high correlation with experiment. Here different computational
alternatives were investigated to assess their impact to the agreement of MMPBSA
calculations with experiment. Seven receptor families with both high-quality
crystal structures and binding affinities were selected. First the performance of
nonpolar solvation models was studied and it was found that the modern approach
that separately models hydrophobic and dispersion interactions dramatically
reduces RMSD's of computed relative binding affinities. The numerical setup of
the Poisson-Boltzmann methods was analyzed next. The data shows that the impact
of grid spacing to the quality of MMPBSA calculations is small: the numerical
error at the grid spacing of 0.5 A is already small enough to be negligible. The
impact of different atomic radius sets and different molecular surface
definitions was further analyzed and weak influences were found on the agreement
with experiment. The influence of solute dielectric constant was also analyzed: a
higher dielectric constant generally improves the overall agreement with
experiment, especially for highly charged binding pockets. The data also showed
that the converged simulations caused slight reduction in the agreement with
experiment. Finally the direction of estimating absolute binding free energies
was briefly explored. Upon correction of the binding-induced rearrangement free
energy and the binding entropy lost, the errors in absolute binding affinities
were also reduced dramatically when the modern nonpolar solvent model was used,
although further developments were apparently necessary to further improve the
MMPBSA methods. (c) 2016 Wiley Periodicals, Inc.
PMID- 27510548
TI - Diabetes: PCSK9 inhibition is not associated with new-onset diabetes.
PMID- 27510549
TI - Anticoagulation therapy: Appropriate dosing of apixaban.
PMID- 27510550
TI - Valvular disease: vWF testing for paravalvular regurgitation during TAVI.
PMID- 27510551
TI - The transport properties of silicon and carbon nanotubes at the atomic scale: a
first-principles study.
AB - Nanotubes are one of the most promising functional materials in nanotechnology.
Silicon nanotubes (SiNTs) have been experimentally validated; they are unique
puckered nanotubular structures unlike carbon nanotubes (CNTs). Although the
electronic and optical properties of SiNTs have been previously studied, their
structure-related capability for electron transport has not been investigated.
Here we report a comparative study of the intrinsic electronic and transport
properties of four pairs of SiNTs and CNTs (one armchair nanotubes (3,3) and
three zigzag nanotubes (5,0), (6,0) and (7,0)) using density functional theory
(DFT) combined with the nonequilibrium Green's function (NEGF) method. All our
investigated systems of SiNTs and CNTs are conductors. Both the armchair SiNTs
and CNTs possess superior electron transport performance to their zigzag
counterparts. Compared with CNTs, SiNTs have more advantages in the high bias
voltage region. Especially, Si(3,3) possesses around double the potential charge
capacity of C(3,3) under the bias voltage of 2.0 V. In particular, the CNT(6,0)
exhibits distinct negative differential resistance (NDR) behavior and the peak
valley ratio (PVR) for C(6,0) is about 1.2.
PMID- 27510552
TI - Identifying protein aggregation mechanisms and quantifying aggregation rates from
combined monomer depletion and continuous scattering.
AB - Parallel temperature initial rates (PTIR) from chromatographic separation of
aggregating protein solutions are combined with continuous simultaneous multiple
sample light scattering (SMSLS) to make quantitative deductions about protein
aggregation kinetics and mechanisms. PTIR determines the rates at which initially
monomeric proteins are converted to aggregates over a range of temperatures,
under initial-rate conditions. Using SMSLS for the same set of conditions
provides time courses of the absolute Rayleigh scattering ratio, IR(t), from
which a potentially different measure of aggregation rates can be quantified. The
present report compares these measures of aggregation rates across a range of
solution conditions that result in different aggregation mechanisms for anti
streptavidin (AS) immunoglobulin gamma-1 (IgG1). The results illustrate how the
two methods provide complementary information when deducing aggregation
mechanisms, as well as cases where they provide new mechanistic details that were
not possible to deduce in previous work. Criteria are presented for when the two
techniques are expected to give equivalent results for quantitative rates, the
potential limitations when solution non-idealities are large, as well as a
comparison of the temperature dependence of AS-IgG1 aggregation rates with
published data for other antibodies.
PMID- 27510553
TI - OxLDL receptor chromatography from live human U937 cells identifies SYK(L) that
regulates phagocytosis of oxLDL.
AB - The binding and activation of macrophages by microscopic aggregates of oxLDL in
the intima of the arteries may be an important step towards atherosclerosis
leading to heart attack and stroke. Microbeads coated with oxLDL were used to
activate, capture and isolate the oxLDL receptor complex from the surface of live
cells. Analysis of the resulting tryptic peptides by liquid chromatography and
tandem mass spectrometry revealed the Spleen Tyrosine Kinase (SYK), and many of
SYK's known interaction network including Fc receptors (FCGR2A, FCER1G and
FCGR1A) Toll receptor 4 (TLR4), receptor kinases like EGFRs, as well as RNA
binding and metabolism proteins. High-intensity precursor ions (~9*E3 to 2*E5
counts) were correlated to peptides and specific phosphopeptides from long
isoform of SYK (SYK-L) by the SEQUEST, OMSSA and X!TANDEM algorithms. Peptides or
phosphopeptides from SYK were observed with the oxLDL-microbeads. Pharmacological
inhibitors of SYK activity significantly reduced the engulfment of oxLDL
microbeads in the presence of serum factors, but had little effect on IgG
phagocytosis. Anti SYK siRNA regulated oxLD engulfment in the context of serum
factors and or SYK-L siRNA significantly inhibited engulfment of oxLDL
microbeads, but not IgG microbeads.
PMID- 27510554
TI - The methylome and transcriptome of fetal skin: implications for scarless healing.
AB - AIM: Fetal skin is known to heal without scarring. In mice, the phenomenon is
observed until the 16-17 day of gestation - the day of transition from scarless
to normal healing. The study aims to identify key methylome and transcriptome
changes following the transition. MATERIALS & METHODS: Methylome and
transcriptome profiles were analyzed in murine dorsal skin using microarray
approach. RESULTS & CONCLUSION: The genes associated with inflammatory response
and hyaluronate degradation showed increased DNA methylation before the
transition, while those involved in embryonic morphogenesis, neuron
differentiation and synapse functions did so after. A number of the methylome
alterations were retained until adulthood and correlated with gene expression,
while the functional associations imply that scarless healing depends on
epigenetic regulation.
PMID- 27510556
TI - Natural product derivative BIO promotes recovery after myocardial infarction via
unique modulation of the cardiac microenvironment.
AB - The cardiac microenvironment includes cardiomyocytes, fibroblasts and
macrophages, which regulate remodeling after myocardial infarction (MI).
Targeting this microenvironment is a novel therapeutic approach for MI. We found
that the natural compound derivative, BIO ((2'Z,3'E)-6-Bromoindirubin-3'-oxime)
modulated the cardiac microenvironment to exert a therapeutic effect on MI. Using
a series of co-culture studies, BIO induced proliferation in cardiomyocytes and
inhibited proliferation in cardiac fibroblasts. BIO produced multiple anti
fibrotic effects in cardiac fibroblasts. In macrophages, BIO inhibited the
expression of pro-inflammatory factors. Significantly, BIO modulated the
molecular crosstalk between cardiac fibroblasts and differentiating macrophages
to induce polarization to the anti-inflammatory M2 phenotype. In the optically
transparent zebrafish-based heart failure model, BIO induced cardiomyocyte
proliferation and completely recovered survival rate. BIO is a known glycogen
synthase kinase-3beta inhibitor, but these effects could not be recapitulated
using the classical inhibitor, lithium chloride; indicating novel therapeutic
effects of BIO. We identified the mechanism of BIO as differential modulation of
p27 protein expression and potent induction of anti-inflammatory interleukin-10.
In a rat MI model, BIO reduced fibrosis and improved cardiac performance.
Histological analysis revealed modulation of the cardiac microenvironment by BIO,
with increased presence of anti-inflammatory M2 macrophages. Our results
demonstrate that BIO produces unique effects in the cardiac microenvironment to
promote recovery post-MI.
PMID- 27510557
TI - Correlation of nanoscale behaviour of forces and macroscale surface wettability.
AB - In this manuscript, we demonstrate a method based on atomic force microscopy
which enables local probing of surface wettability. The maximum pull-off force,
obtained from force spectroscopy shows a remarkable correlation with the
macroscopically observed water contact angle, measured over a wide variety of
surfaces starting from hydrophilic, all the way through to hydrophobic ones. This
relationship, consequently, facilitates the establishment of a universal
behaviour. The adhesion forces scale with the polar component of surface energy.
However, no such relation could be established with the dispersive component.
Hence, we postulate that the force(s) which enable us to correlate the force
spectroscopy data measured on the nanoscale to the macroscopic contact angle are
primarily arising from electrostatic-dipole-dipole interactions at the solid
liquid interface. London forces play less of a role. This effect in is line with
density functional theory (DFT) calculations suggesting a higher degree of
hydroxylation of hydrophilic surfaces. This result shows that molecular
simulations and measurements on an atomic scale can be extrapolated to
macroscopic surface wetting problems.
PMID- 27510555
TI - Recent advances in the development and application of nanoelectrodes.
AB - Nanoelectrodes have key advantages compared to electrodes of conventional size
and are the tool of choice for numerous applications in both fundamental
electrochemistry research and bioelectrochemical analysis. This Minireview
summarizes recent advances in the development, characterization, and use of
nanoelectrodes in nanoscale electroanalytical chemistry. Methods of nanoelectrode
preparation include laser-pulled glass-sealed metal nanoelectrodes, mass-produced
nanoelectrodes, carbon nanotube based and carbon-filled nanopipettes, and
tunneling nanoelectrodes. Several new topics of their recent application are
covered, which include the use of nanoelectrodes for electrochemical imaging at
ultrahigh spatial resolution, imaging with nanoelectrodes and nanopipettes,
electrochemical analysis of single cells, single enzymes, and single
nanoparticles, and the use of nanoelectrodes to understand single nanobubbles.
PMID- 27510558
TI - Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful
for detecting hypothyroidism?
AB - AIM: To determine if visual assessment of the attenuation of morphologically
normal appearing thyroid glands on unenhanced computed tomography (CT) of the
chest is useful for identifying patients with decreased thyroid function.
MATERIALS AND METHODS: This was a retrospective study of 765 patients who
underwent both unenhanced CT of the chest and thyroid function tests performed
within 1 year of the CT examination. Attenuation of the thyroid gland was
visually assessed in each patient relative to the attenuation of the surrounding
muscles to categorise the gland as "low attenuation" (attenuation similar to
surrounding muscles) or "high attenuation" (attenuation greater than surrounding
muscles). Thyroid attenuation was quantitatively measured in each case to
determine the validity of the visual assessment. Results of thyroid function
tests were used to classify thyroid function as hypothyroid, euthyroid, or
hyperthyroid. Data were analysed to determine the relationship between visual
assessment of thyroid attenuation and status of thyroid function. RESULTS:
Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients.
Nearly half (47%) of the patients with low-attenuation thyroids had
hypofunctioning thyroid glands. Compared to patients with high-attenuation
thyroids, patients with low-attenuation thyroids were significantly more likely
to have decreased thyroid function (clinical and subclinical hypothyroidism) and
significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of
thyroid attenuation confirmed the validity of the visual assessment. CONCLUSION:
Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT
of the chest is strongly associated with decreased thyroid function.
PMID- 27510559
TI - Thermal ablation for hepatocellular carcinoma: a large-scale analysis of long
term outcome and prognostic factors.
AB - AIM: To investigate the long-term outcome and prognostic factors when treating
hepatocellular carcinoma (HCC) with thermal ablation. MATERIALS AND METHODS: A
total of 846 HCC patients, diagnosed histopathologically and/or radiologically,
underwent thermal ablation from October 2001 to May 2013. Thermal ablation
included both radiofrequency ablation (RFA) and microwave ablation (MWA), and was
performed by percutaneous, open, and laparoscopic approaches. Clinical data,
especially focused on disease-free survival, were retrospectively analysed by
univariate and multivariate analyses. RESULTS: A total of 1,185 thermal ablation
treatments were performed, corresponding to 1,240 tumours. The complete ablation
rate was 97.1%. The 12-, 24-, 36-, and 60-month disease-free survival rates after
thermal ablation were 72.3%, 52.7%, 33.5%, and 16.1%, respectively. Multivariate
analysis indicated that the serum alkaline phosphatase levels (ALP) and the
number of tumours were independent risk factors affecting disease-free survival.
The 12-, 36-, 60-, 84-, and 120-month overall survival rates of all patients were
92.9%, 74.7%, 58.1%, 41.3%, and 15.8%, respectively. Multivariate analysis
indicated that age, ALP, number of tumours, and treatment sessions per case were
independent risk factors related to overall survival. CONCLUSIONS: Thermal
ablation was a relatively safe and effective procedure. Patients with increased
serum ALP levels and/or multiple tumours had a higher incidence of recurrence and
poorer prognosis, and therefore, should be monitored closely in clinical
practice.
PMID- 27510560
TI - Prolonged drug-induced myoclonus: is it related to palonosetron?
AB - We report a case of drug-induced myoclonus possibly related to palonosetron, a
second-generation 5-hydroxytryptamine-3 receptor antagonist which was
administered as a prophylaxis for postoperative nausea and vomiting in a 28-year
old female. The recurrent episodes of myoclonus jerk involving the head, neck and
shoulder persisted for a period of 4 days. The patient also exhibited an episode
of severe bradycardia leading to hypotension 7 h after surgery. To our knowledge,
this is the first report presenting these adverse events potentially associated
with the use of palonosetron.
PMID- 27510561
TI - Magnesium-doped Zinc Oxide as Electron Selective Contact Layers for Efficient
Perovskite Solar Cells.
AB - The electron-selective contact layer (ESL) in organometal halide-based perovskite
solar cells (PSCs) determines not only the power conversion efficiency (PCE) but
also the thermostability of PSCs. To improve the thermostability of ZnO-based
PSCs, we developed Mg-doped ZnO [Zn1-x Mgx O (ZMO)] as a high optical
transmittance ESL for the methylammonium lead trihalide perovskite absorber [CH3
NH3 PbI3 ]. We further investigated the optical and electrical properties of the
ESL films with Mg contents of 0-30 mol % and the corresponding devices. We
achieved a maximum PCE of 16.5 % with improved thermal stability of CH3 NH3 PbI3
on ESL with the optimal ZMO (0.4 m) containing 10 mol % Mg. Moreover, this
optimized ZMO PSC exhibited significantly improved durability and photostability
owing to the improved chemical/photochemical stability of the wider optical
bandgap ZMO.
PMID- 27510562
TI - Gene selection for cancer classification with the help of bees.
AB - BACKGROUND: Development of biologically relevant models from gene expression data
notably, microarray data has become a topic of great interest in the field of
bioinformatics and clinical genetics and oncology. Only a small number of gene
expression data compared to the total number of genes explored possess a
significant correlation with a certain phenotype. Gene selection enables
researchers to obtain substantial insight into the genetic nature of the disease
and the mechanisms responsible for it. Besides improvement of the performance of
cancer classification, it can also cut down the time and cost of medical
diagnoses. METHODS: This study presents a modified Artificial Bee Colony
Algorithm (ABC) to select minimum number of genes that are deemed to be
significant for cancer along with improvement of predictive accuracy. The search
equation of ABC is believed to be good at exploration but poor at exploitation.
To overcome this limitation we have modified the ABC algorithm by incorporating
the concept of pheromones which is one of the major components of Ant Colony
Optimization (ACO) algorithm and a new operation in which successive bees
communicate to share their findings. RESULTS: The proposed algorithm is evaluated
using a suite of ten publicly available datasets after the parameters are tuned
scientifically with one of the datasets. Obtained results are compared to other
works that used the same datasets. The performance of the proposed method is
proved to be superior. CONCLUSION: The method presented in this paper can provide
subset of genes leading to more accurate classification results while the number
of selected genes is smaller. Additionally, the proposed modified Artificial Bee
Colony Algorithm could conceivably be applied to problems in other areas as well.
PMID- 27510563
TI - Ectopic expression of MCAM/MUC18 increases in vitro motility and invasiveness,
but decreases in vivo tumorigenesis and metastasis of a mouse melanoma K1735-9
subline in a syngeneic mouse model.
AB - Ectopic expression of MCAM/MUC18, a cell adhesion molecule in the immunoglobulin
like gene superfamily, induces two moMCAM/MUC18-minus, non-metastatic mouse
melanoma K1735 sublines, K3 (tumor+/metlow) and K10 (tumor-/metlow), to
metastasize to lungs in a syngeneic C3H mouse model. In this report, we extended
investigation of effects of moMCAM/MUC18 expression on tumorigenesis and
metastasis in another lowly metastatic, however highly tumorigenic moMCAM/MUC18
minus mouse melanoma K1735 subline, K9 (tumor+++/metlow). We transfected this
subline with the moMCAM/MUC18 cDNA, selected for G418-resistant clones with
different expression levels of moMCAM/MUC18, and used them for testing effects of
MCAM/MUC18 expression on in vitro growth rate, motility, and invasiveness, in
vivo subcutaneous tumor growth, and pulmonary metastasis in syngeneic C3H brown
mice. Similar to K3 and K10 cells, increased expression of MCAM/MUC18 in K9 cells
did not significantly affect in vitro growth rate, but increased in vitro
motility and invasiveness. Surprisingly, increased expression of MCAM/MUC18 in K9
cells decreased their induction of tumorigenesis and suppressed their
establishment of pulmonary nodules in syngeneic C3H brown mice. We concluded that
increased MCAM/MUC18 expression in K9 subline increased in vitro epithelial-to
mesenchymal transition; however, it suppressed in vivo tumorigenicity and
metastasis. Thus MCAM/MUC18 acts as a tumor and metastasis suppressor for the K9
subline, different from its role in other K1735 sublines, K3 and K10. Different
intrinsic co-factors in different K1735 sublines, which modulate the functions of
MCAM/MUC18 in the cells that interact differently to the tumor microenvironment,
may render sublines manifest differently in tumorigenicity and metastasis in
vivo.
PMID- 27510564
TI - Genomes of Ellobius species provide insight into the evolutionary dynamics of
mammalian sex chromosomes.
AB - The X and Y sex chromosomes of placental mammals show hallmarks of a tumultuous
evolutionary past. The X Chromosome has a rich and conserved gene content, while
the Y Chromosome has lost most of its genes. In the Transcaucasian mole vole
Ellobius lutescens, the Y Chromosome including Sry has been lost, and both
females and males have a 17,X diploid karyotype. Similarly, the closely related
Ellobius talpinus, has a 54,XX karyotype in both females and males. Here, we
report the sequencing and assembly of the E. lutescens and E. talpinus genomes.
The results indicate that the loss of the Y Chromosome in E. lutescens and E.
talpinus occurred in two independent events. Four functional homologs of mouse Y
Chromosomal genes were detected in both female and male E. lutescens, of which
three were also detected in the E. talpinus genome. One of these is Eif2s3y,
known as the only Y-derived gene that is crucial for successful male meiosis.
Female and male E. lutescens can carry one and the same X Chromosome with a
largely conserved gene content, including all genes known to function in X
Chromosome inactivation. The availability of the genomes of these mole vole
species provides unique models to study the dynamics of sex chromosome evolution.
PMID- 27510565
TI - Genomic variation within alpha satellite DNA influences centromere location on
human chromosomes with metastable epialleles.
AB - Alpha satellite is a tandemly organized type of repetitive DNA that comprises 5%
of the genome and is found at all human centromeres. A defined number of 171-bp
monomers are organized into chromosome-specific higher-order repeats (HORs) that
are reiterated thousands of times. At least half of all human chromosomes have
two or more distinct HOR alpha satellite arrays within their centromere regions.
We previously showed that the two alpha satellite arrays of Homo sapiens
Chromosome 17 (HSA17), D17Z1 and D17Z1-B, behave as centromeric epialleles, that
is, the centromere, defined by chromatin containing the centromeric histone
variant CENPA and recruitment of other centromere proteins, can form at either
D17Z1 or D17Z1-B. Some individuals in the human population are functional
heterozygotes in that D17Z1 is the active centromere on one homolog and D17Z1-B
is active on the other. In this study, we aimed to understand the molecular basis
for how centromere location is determined on HSA17. Specifically, we focused on
D17Z1 genomic variation as a driver of epiallele formation. We found that D17Z1
arrays that are predominantly composed of HOR size and sequence variants were
functionally less competent. They either recruited decreased amounts of the
centromere-specific histone variant CENPA and the HSA17 was mitotically unstable,
or alternatively, the centromere was assembled at D17Z1-B and the HSA17 was
stable. Our study demonstrates that genomic variation within highly repetitive,
noncoding DNA of human centromere regions has a pronounced impact on genome
stability and basic chromosomal function.
PMID- 27510567
TI - Prediction of response to tapentadol in chronic low back pain.
AB - BACKGROUND: Many chronic low back pain (cLBP) patients do not satisfactorily
respond to treatment. The knowledge of responders and non-responders before
initiating treatment would improve decision making and reduce health care costs.
The aims of this exploratory prediction study in cLBP patients treated with
tapentadol were to identify predictors of treatment outcome based on baseline
characteristics, to evaluate quality-of-life and functionality as alternative
outcome parameters and to develop nomograms to calculate the individual
probability of response. METHODS: In a retrospective analysis of an open-label
phase 3b trial, 46 baseline characteristics were included into statistical
prediction modelling. One hundred and twenty-one patients were followed up during
the titration and treatment period and 67 patients were analysed who discontinued
the trial. RESULTS: Demographic data were not relevant for response prediction.
Nine baseline co-variables were robust: painDETECT score, intensity of burning
and painful attacks, SF36 Health Survey score (MCS, PCS), EuroQol-5, Hospital
Anxiety/Depression Scale. Gender had a minor influence. Alternative outcomes
(quality-of-life, functionality) were more important for response prediction than
conventional pain intensity measures. Neuropathic symptoms (high painDETECT
score) had a positive predictive validity. Painful attacks and classical yellow
flags (depression, anxiety) negatively influenced the treatment response. High
depression scores, female gender and low burning predicted discontinuation during
titration. CONCLUSION: In this exploratory study, predictive baseline
characteristics have been identified that can be used to calculate the individual
probability of tapentadol response in cLBP. The small sample size in relation to
the number of initial variables is a limitation of this approach. SIGNIFICANCE:
Predictors for treatment response of tapentadol were identified in patients with
chronic low back pain based on clinical pre-treatment characteristics that can
guide personalized treatment. Quality-of-life and functionality were the most
relevant outcomes for response prediction.
PMID- 27510566
TI - Pangolin genomes and the evolution of mammalian scales and immunity.
AB - Pangolins, unique mammals with scales over most of their body, no teeth, poor
vision, and an acute olfactory system, comprise the only placental order
(Pholidota) without a whole-genome map. To investigate pangolin biology and
evolution, we developed genome assemblies of the Malayan (Manis javanica) and
Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon
(IFNE), exclusively expressed in epithelial cells and important in skin and
mucosal immunity, is pseudogenized in all African and Asian pangolin species that
we examined, perhaps impacting resistance to infection. We propose that scale
development was an innovation that provided protection against injuries or stress
and reduced pangolin vulnerability to infection. Further evidence of specialized
adaptations was evident from positively selected genes involving immunity-related
pathways, inflammation, energy storage and metabolism, muscular and nervous
systems, and scale/hair development. Olfactory receptor gene families are
significantly expanded in pangolins, reflecting their well-developed olfaction
system. This study provides insights into mammalian adaptation and functional
diversification, new research tools and questions, and perhaps a new natural IFNE
deficient animal model for studying mammalian immunity.
PMID- 27510568
TI - Porphyromonas pogonae identification from a soft tissue infection: The first
human case.
AB - We report a first human case of Porphyromonas pogonae causing soft tissue
infection in a patient with open fracture. Strong beta-hemolytic, aerotolerant,
and non-pigmented gram-negative coccobacilli which matched Porphyromonas pogonae
by PCR for 16S rRNA genes were identified from the pus specimen. The clinical
course of the patient improved with repeated surgical drainage and tigecycline
administration.
PMID- 27510569
TI - First isolation of Clostridium indolis in a patient with chronic osteitis: a case
report and literature review of human infections related to Clostridium
saccharolyticum group species.
AB - Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus
belonging to the Clostridium saccharolyticum group. Its clinical significance in
human remains poorly known. We describe the first case of osteitis related to C.
indolis, identified by MALDI-TOF mass spectrometry and provide a literature
review of human infections related to C. saccharolyticum group species.
PMID- 27510570
TI - Exposure to light and darkness and its influence on physiological measures of
intensive care unit patients-a systematic literature review.
AB - Sleep-wake patterns are often significantly disturbed in critically ill patients.
This disturbance is closely linked to secondary brain dysfunctions in these
patients. Sedation not only impairs sleep quality in ICU patients but also has
detrimental effects on short- and long-term outcome. In other contexts, light
therapy has been proven to be effective in maintaining and resynchronizing
circadian rhythmicity in humans. The objective of this systematic review was to
analyse studies that investigated the effect of exposure to light or darkness on
physiological measures and clinical outcomes of adult ICU patients. Studies were
systematically identified by searching electronic bibliographic databases (The
Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
2002) and MEDLINE via PubMed). The search algorithm identified a total of 156
articles, 10 of which were taken into final review. These 10 selected articles
included 3 were monocentric RCTs, five prospective cohort studies, one
retrospective cohort study, and one manuscript that included a partial systematic
review of the literature. Included trials were published between 2007 and 2015.
Five of these studies used multiple intervention approaches while four trials
used a single intervention approach. Among all studies, 1,278 patients were
analysed (489 prospectively). There was a high heterogeneity among the studies in
terms of applied intervention and outcome measures. The most frequent
methodological limitations were a lack of precise definitions regarding the
illuminance and the light spectrum utilised. The analyses indicate that further
studies including clearly defined interventions with objective outcome measures,
as these are currently lacking, would add significant knowledge to this new field
of research.
PMID- 27510571
TI - Structured Instruction With Modified Storybooks to Teach Morphosyntax and
Vocabulary to Preschoolers Who are Deaf/Hard of Hearing.
AB - Children who are deaf/hard of hearing (D/HH) are at risk for diminished
morphosyntactical and vocabulary development. The purpose of this study was to
examine the effects of repeated reading combined with structured instruction.
Targets were a morphosyntactical form and novel vocabulary words. Participants
were 3 preschoolers who are D/HH who were receiving instruction with an oral
approach. Data from a multiple baseline design indicated that all children
acquired the targeted skills and demonstrated high levels of generalization of
these skills to untrained context. Implications for teaching young children who
are D/HH using repeated storybook reading are discussed.
PMID- 27510572
TI - The BA-HEF trial in Africa: a welcome addition to heart failure history.
PMID- 27510573
TI - Chemoprevention of basal cell carcinoma.
PMID- 27510574
TI - Punctate palmoplantar keratoderma type 1 with a novel AAGAB frameshift mutation:
intrafamilial phenotype variation due to ageing.
PMID- 27510575
TI - Long-term Effects of Managed Care.
AB - Managed care (MC) plans have been introduced to curb the ever increasing health
care costs. Many previous studies on effectiveness lacked a long-term
perspective; hence, the sustainability of (possible) savings remains unclear.
Moreover, because of their incentives, MC plans are susceptible to under
provision of care. Most of these possibly negative effects can only be observed
in the long-term. This paper analyzes the long-term effects of MC plans on cost
savings, mortality, and the use of service, using administrative data from a
large Swiss health insurer. The identification is based on a propensity-score
matching approach, where individuals who enter an MC plan are compared over 10
years to individuals who remain in a standard fee-for-service plan. Cost savings
are substantial and sustainable, and the mortality rate is lower in MC plans.
Cost savings are driven by fewer consultations and fewer days in hospital care,
although the probability of visiting a provider at least once per year is similar
or even higher for persons in MC plans. Copyright (c) 2016 John Wiley & Sons,
Ltd.
PMID- 27510576
TI - Taylor line swimming in microchannels and cubic lattices of obstacles.
AB - Microorganisms naturally move in microstructured fluids. Using the simulation
method of multi-particle collision dynamics, we study in two dimensions an
undulatory Taylor line swimming in a microchannel and in a cubic lattice of
obstacles, which represent simple forms of a microstructured environment. In the
microchannel the Taylor line swims at an acute angle along a channel wall with a
clearly enhanced swimming speed due to hydrodynamic interactions with the
bounding wall. While in a dilute obstacle lattice swimming speed is also
enhanced, a dense obstacle lattice gives rise to geometric swimming. This new
type of swimming is characterized by a drastically increased swimming speed.
Since the Taylor line has to fit into the free space of the obstacle lattice, the
swimming speed is close to the phase velocity of the bending wave traveling along
the Taylor line. While adjusting its swimming motion within the lattice, the
Taylor line chooses a specific swimming direction, which we classify by a lattice
vector. When plotting the swimming velocity versus the magnitude of the lattice
vector, all our data collapse on a single master curve. Finally, we also report
more complex trajectories within the obstacle lattice.
PMID- 27510577
TI - Long-term HIV-1 infection induces an antiviral state in primary macrophages.
AB - HIV-1 infection is thought to impair type I interferon (IFN-I) production in
macrophages, a cell type that is also relatively resistant to HIV-1 cytotoxic
effects. Here, we show that monocyte differentiation into macrophages by M-CSF
led to cell proliferation and susceptibility to HIV-1 infection that induced cell
cycle arrest and increased cell death. Established HIV-1 infection of monocyte
derived macrophages induced the upregulation of the pattern recognition receptors
MDA5 and Rig-I that serve as virus sensors; production of interferon-beta, and
transcription of interferon-stimulated genes including CXCL10. Infected
macrophages showed increased expression of p21 and subsequent inactivation of
cyclin-CDK2 activity leading to a hypo-phosphorylated active retinoblastoma
protein (pRb) and deactivation of E2F1-dependent transcription and CDK1
downregulation. Additionally, HIV-1 infection limited deoxynucleotide pool by
downregulation of the ribonucleotide reductase subunit R2 (RNR2) and reactivation
of the HIV-1 restriction factor SAMHD1 together with increased cell death. In
conclusion, HIV-1 induced an innate antiviral mechanism associated to IFN-I
production, interferon stimulated gene activation, and p21-mediated G2/M arrest
leading to elevated levels of cell death in monocyte derived macrophages.
Upregulation of MDA5 and Rig-I may serve as targets for the development of
antiviral strategies leading to the elimination of HIV-1 infected cells.
PMID- 27510578
TI - Electrophilic iodination: a gateway to high iodine compounds and energetic
materials.
AB - A large number of iodine atoms can be introduced into a single molecule in a one
pot reaction using trifluoroperacetic acid-mediated electrophilic iodination
methodology. The scope of this reaction was investigated extensively using
several pyrazole substrates which resulted in nine polyiodo pyrazole compounds
with iodine content as high as 80%. This synthetic methodology was also utilized
successfully for iodination of benzimidazoles. Tetraiodobenzimidazole was
nitrated with 100% nitric acid to give a high yield of 4,5,6,7-tetranitro-1H
benzimidazol-2(3H)-one (14). All of these materials were fully characterized and
compounds 5, 9, 10 and 14 were confirmed further with single crystal X-ray
analysis. High density, positive oxygen balance, and very good impact sensitivity
values characterize 14. For the first time, two 1,2,5-oxadiazole-N-oxide rings
were introduced into a benzimidazole ring (11) which remarkably improves the
stability of oxadiazole-N-oxide compounds.
PMID- 27510579
TI - Retrieval-Based Model Accounts for Striking Profile of Episodic Memory and
Generalization.
AB - A fundamental theoretical tension exists between the role of the hippocampus in
generalizing across a set of related episodes, and in supporting memory for
individual episodes. Whilst the former requires an appreciation of the
commonalities across episodes, the latter emphasizes the representation of the
specifics of individual experiences. We developed a novel version of the
hippocampal-dependent paired associate inference (PAI) paradigm, which afforded
us the unique opportunity to investigate the relationship between episodic memory
and generalization in parallel. Across four experiments, we provide surprising
evidence that the overlap between object pairs in the PAI paradigm results in a
marked loss of episodic memory. Critically, however, we demonstrate that superior
generalization ability was associated with stronger episodic memory. Through
computational simulations we show that this striking profile of behavioral
findings is best accounted for by a mechanism by which generalization occurs at
the point of retrieval, through the recombination of related episodes on the fly.
Taken together, our study offers new insights into the intricate relationship
between episodic memory and generalization, and constrains theories of the
mechanisms by which the hippocampus supports generalization.
PMID- 27510580
TI - A Bioorthogonal Near-Infrared Fluorogenic Probe for mRNA Detection.
AB - There is significant interest in developing methods that visualize and detect
RNA. Bioorthogonal template-driven tetrazine ligations could be a powerful route
to visualizing nucleic acids in native cells, yet past work has been limited with
respect to the diversity of fluorogens that can be activated via a tetrazine
reaction. Herein we report a novel bioorthogonal tetrazine uncaging reaction that
harnesses tetrazine reactivity to unmask vinyl ether caged fluorophores spanning
the visible spectrum, including a near-infrared (NIR)-emitting cyanine dye. Vinyl
ether caged fluorophores and tetrazine partners are conjugated to high-affinity
antisense nucleic acid probes, which show highly selective fluorogenic reactivity
when annealed to their respective target RNA sequences. A target sequence in the
3' untranslated region of an expressed mRNA was detected in live cells employing
appropriate nucleic acid probes bearing a tetrazine-reactive NIR fluorogen. Given
the expansion of tetrazine fluorogenic chemistry to NIR dyes, we believe highly
selective proximity-induced fluorogenic tetrazine reactions could find broad uses
in illuminating endogenous biomolecules in cells and tissues.
PMID- 27510582
TI - Original Research: Potential ocular protection and dynamic observation of
Polygonatum sibiricum polysaccharide against streptozocin-induced diabetic rats'
model.
AB - Ocular complications associated with diabetes mellitus are progressive and
becoming one of the most important causes of morbidity worldwide. The purpose of
the study is to evaluate the protective effect of Polygonatum sibiricum
polysaccharide, an important component of Polygonatum sibiricum, on ocular
complications in streptozotocin-induced diabetes mellitus rats. Sprague Dawley
rats were made diabetic with streptozotocin(60 mg/kg, i.v.) and then the rats
were treated with Polygonatum sibiricum polysaccharide 200, 400 and 800 mg/kg.d
by gavage for 12 weeks. Biochemical analysis indicated that Polygonatum sibiricum
polysaccharide lowered the levels of fasting blood glucose and glycated
hemoglobin in blood and elevated the levels of insulin and C-peptide in plasma of
diabetes mellitus rats in a dose-dependent manner. Physical measurements revealed
that Polygonatum sibiricum polysaccharide improved clinical symptoms of
polydipsia, polyphagia, polyuria and weight loss in diabetes mellitus rats. The
content of malondialdehyde and activity of superoxide dismutase in plasma were
determined, and the data showed Polygonatum sibiricum polysaccharide suppressed
oxidative stress reaction. Lens opacification was observed using slit lamp
illumination, and the data showed Polygonatum sibiricum polysaccharide delayed
cataract progression in a dose-dependent manner. Electroretinogram showed
Polygonatum sibiricum polysaccharide treatment reversed the decrease of
electroretinogram b and OPs2 waves' amplitudes. Flash-visual evoked potential
test indicated that the peak time of P2 wave was prolonged, and the amplitude of
N2-P2 was lowered in diabetes mellitus group, and Polygonatum sibiricum
polysaccharide suppressed these changes. Fundus fluorescein angiography showed
Polygonatum sibiricum polysaccharide alleviated the retinal vasculopathy in a
dose-dependent manner. In conclusion, these results suggest that the
administration of Polygonatum sibiricum polysaccharide slows the progression of
diabetic retinopathy and cataract through alleviating hyperglycemia and reducing
oxidative stress in streptozotocin-induced diabetes mellitus rats.
PMID- 27510581
TI - Original Research: Effect of various dietary fats on fatty acid profile in duck
liver: Efficient conversion of short-chain to long-chain omega-3 fatty acids.
AB - Omega-3 fatty acids, especially long-chain omega-3 fatty acids, have been
associated with potential health benefits for chronic disease prevention. Our
previous studies found that dietary omega-3 fatty acids could accumulate in the
meat and eggs in a duck model. This study was to reveal the effects of various
dietary fats on fatty acid profile and conversion of omega-3 fatty acids in duck
liver. Female Shan Partridge Ducks were randomly assigned to five dietary
treatments, each consisting of 6 replicates of 30 birds. The experimental diets
substituted the basal diet by 2% of flaxseed oil, rapeseed oil, beef tallow, or
fish oil, respectively. In addition, a dose response study was further conducted
for flaxseed and fish oil diets at 0.5%, 1%, and 2%, respectively. At the end of
the five-week treatment, fatty acids were extracted from the liver samples and
analyzed by GC-FID. As expected, the total omega-3 fatty acids and the ratio of
total omega-3/omega-6 significantly increased in both flaxseed and fish oil
groups when compared with the control diet. No significant change of total
saturated fatty acids or omega-3 fatty acids was found in both rapeseed and beef
tallow groups. The dose response study further indicated that 59-81% of the short
chain omega-3 ALA in flaxseed oil-fed group was efficiently converted to long
chain DHA in the duck liver, whereas 1% of dietary flaxseed oil could produce an
equivalent level of DHA as 0.5% of dietary fish oil. The more omega-3 fatty
acids, the less omega-6 fatty acids in the duck liver. Taken together, this study
showed the fatty acid profiling in the duck liver after various dietary fat
consumption, provided insight into a dose response change of omega-3 fatty acids,
indicated an efficient conversion of short- to long-chain omega-3 fatty acid, and
suggested alternative long-chain omega-3 fatty acid-enriched duck products for
human health benefits.
PMID- 27510583
TI - Toll-like receptor 4 contributes to acute kidney injury after cardiopulmonary
resuscitation in mice.
AB - Toll-like receptor 4 (TLR4) activation mediates renal injury in regional ischemia
and reperfusion (I/R) models generated by clamping renal pedicles. However, it
remains unclear whether TLR4 is causal in the kidney injury following global I/R
induced by cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The
present study used wild-type (C3H/HeN) and TLR4-mutant (C3H/HeJ) mice to produce
the CA/CPR model. CA was induced by injection of cold KCl and left untreated for
different time periods. After resuscitation (72 h), the level of blood urea
nitrogen (BUN) and serum creatinine (Scr), as well as histological changes in
renal tissue were assessed to evaluate the severity of acute kidney injury (AKI).
The expression of TLR4, intercellular adhesion molecule-1 (ICAM-1),
myeloperoxidase (MPO) and growth-regulated oncogene-beta (GRO-beta) in kidney
tissues was detected. The results demonstrated that the levels of Scr and BUN
increased significantly in C3H/HeN and C3H/HeJ mice after CPR. CPR also resulted
in increased expression of TLR4, ICAM-1, GRO-beta and MPO in a CA-duration
dependent manner. However, there was decreased expression of ICAM-1, GRO-beta and
MPO in C3H/HeJ mice compared with that in C3H/HeN mice. C3H/HeJ mice were
resistant to AKI as demonstrated by the minor changes in renal histology and
function following CPR. In conclusion, mice suffered from AKI after successful
CPR and severe AKI occurred in mice with prolonged CA duration. TLR4 and its
downstream signaling events that promote neutrophil infiltration via ICAM-1 and
GRO-beta may be important in mediating inflammatory responses to renal injury
after CPR.
PMID- 27510584
TI - Determination and pharmacokinetic properties of arsenic speciation in Xiao-Er-Zhi
Bao-Wan by high-performance liquid chromatography with inductively coupled plasma
mass spectrometry.
AB - A method of high performance liquid chromatography with a Hamilton PRP-X100 ion
exchange column (250 * 4.1 mm id, 10 MUm) coupled to inductively coupled plasma
mass spectrometry was employed to generate a full concentration-time profile of
arsenic speciation after oral administration. The results exhibited good
linearity and revealed that, in the pills, the average arsenic concentration was
10105.4 +/- 380.7 mg/kg, and in the water extraction solution, the inorganic
As(III) and As(V) concentrations were 220.1 +/- 12.6 and 45.5 +/- 2.3 mg/kg,
respectively. No trace of monomethyl arsenic acid was detected in any of the
plasma samples. We then successfully applied the established methodology to
examine the pharmacokinetics of arsenic speciation. The resulting data revealed
that, after oral administration in rats, the plasma concentration of each arsenic
species reached Cmax shortly after initial dosing, and that the distribution and
elimination of As(V) was faster than that of As(III) and dimethyl arsenic acid.
Additionally, the t1/2 values of As(V), As(III), and dimethyl arsenic acid were
3.4 +/- 1.6, 14.3 +/- 4.0, and 19.9 +/- 1.6 h, respectively. This study provides
references for the determination of arsenic speciation in mineral-containing
medicines and could serve as a useful tool in measuring the true toxicity in
traditional medicines that contain them.
PMID- 27510587
TI - IFSO 2016 21st World Congress.
PMID- 27510586
TI - Pouch Reshaping for Significant Weight Regain after Roux-en-Y Gastric Bypass.
AB - BACKGROUND: Significant weight regain after Roux-en-Y gastric bypass (RYGB)
occurs in around 20 % of patients in the long term. Anatomical reasons include
dilatation of the gastric pouch and/or the pouch-jejunal anastomosis, leading to
loss of restriction. Pouch reshaping (PR) aims at reestablishing restriction with
a subsequent feeling of satiety. This study reports the outcome of PR embedded in
a multidisciplinary treatment pathway. METHODS: Twenty-six patients after PR for
weight regain >30 % following RYGB in a university hospital between October 2010
and March 2016 were analyzed. Excluded were patients with PR for gastro-gastric
fistulae, hypoglycemia, candy cane syndrome, and concomitant alteration of limb
lengths. PR consisted in laparoscopic lateral resection of the gastric pouch, the
anastomosis and the proximal 5 cm of the alimentary limb over a 32F bougie.
RESULTS: Median follow-up after PR was 48 months (range 24-60). Median BMI at PR
was 39.1 kg/m2 (32.7-59.1). Median operation time was 85 min (25-190), and median
length of stay was 3 days (1-35). Minor complications (grade <= 2) occurred in
seven (27 %) patients and major complications (grade >= 3) in four patients (15
%). Nadir BMI and %EBMIL after PR were 32.9 kg/m2 and 43.3 %, reached after a
median of 12 months (3-48). Comorbidities were resolved in 81 %. After 48 months,
median BMI was 33.8 kg/m2 (20.4-49.2) and %EBMIL was 61.4 (39.1-121.2).
CONCLUSIONS: Used selectively in a multidisciplinary treatment pathway, PR leads
to prolonged weight stabilization around the previous nadir. However, its
associated perioperative morbidity must not be disregarded.
PMID- 27510585
TI - Characterization of the Kynurenine Pathway in CD8+ Human Primary Monocyte-Derived
Dendritic Cells.
AB - The kynurenine (KYN) pathway (KP) is a major degradative pathway of the amino
acid, L-tryptophan (TRP), that ultimately leads to the anabolism of the essential
pyridine nucleotide, nicotinamide adenine dinucleotide. TRP catabolism results in
the production of several important metabolites, including the major immune
tolerance-inducing metabolite KYN, and the neurotoxin and excitotoxin quinolinic
acid. Dendritic cells (DCs) have been shown to mediate immunoregulatory roles
that mediated by TRP catabolism. However, characterization of the KP in human DCs
has so far only been partly delineated. It is critical to understand which KP
enzymes are expressed and which KP metabolites are produced to be able to
understand their regulatory effects on the immune response. In this study, we
characterized the KP in human monocyte-derived DCs (MDDCs) in comparison with the
human primary macrophages using RT-PCR, high-pressure gas chromatography, mass
spectrometry, and immunocytochemistry. Our results show that the KP is entirely
expressed in human MDDC. Following activation of the KP using interferon gamma,
MDDCs can mediate apoptosis of T h cells in vitro. Understanding the molecular
mechanisms regulating KP metabolism in MDDCs may provide renewed insight for the
development of novel therapeutics aimed at modulating immunological effects and
peripheral tolerance.
PMID- 27510588
TI - Primary Inadequate Weight Loss After Roux-en-Y Gastric Bypass Is not Associated
with Poor Cardiovascular or Metabolic Outcomes: Experience from a Single
Institution.
AB - BACKGROUND: It is well accepted that bariatric surgery has cardiovascular and
metabolic effects independent of weight loss. METHODS: Weight loss outcomes of
patients undergoing Roux-en-Y gastric bypass (RYGB) at a high volume referral
center were collected at 1 year postoperatively. Patients with failed primary
weight loss were identified. Primary inadequate weight loss was defined as total
body weight loss less than 15 %. Changes in hypertension (HTN), dyslipidemia,
type 2 diabetes mellitus (T2DM), and metabolic syndrome profiles were
investigated using Student's t test. RESULTS: A total of 2500 patients underwent
RYGB from the years 2001-2013 at our institution. One hundred five (4.2 %)
patients had primary inadequate weight loss. Within this cohort, 81 (77.1 %)
patients had hypertension, 67 (63.8 %) had dyslipidemia, 53 (50.5 %) had type 2
diabetes mellitus, and 66 (62.9 %) patients had metabolic syndrome. At 1 year
postoperatively, all metabolic parameters were significantly improved. Measures
of metabolic disease included high-density lipoprotein (HDL) (46.3 +/- 11.6
versus 54.1 +/- 12.7 mg/dL, p < 0.01), low-density lipoprotein (LDL) (103.6 +/-
35.8 versus 89.2 +/- 30.0 mg/dL, p < 0.01), triglycerides (177.3 +/- 139.1 versus
117.6 +/- 59.3 mg/dL, p < 0.01), mean plasma glucose (128.9 +/- 55.3 versus 102.7
+/- 27.3 mg/dL, p < 0.01), and hemoglobin A1C (7.3 +/- 1.9 versus 6.1 +/- 1.0 %,
p < 0.01). HTN was noted to improve in 27 (33.3 %) patients based on a decrease
in the number of anti-hypertensives used (1.7 +/- 1.0 versus 1.3 +/- 1.3, p <
0.01), and 21 (31.8 %) patients had resolution of their metabolic syndrome.
CONCLUSION: Improvement in cardiometabolic comorbidities still occurs despite
suboptimal weight loss following RYGB.
PMID- 27510589
TI - Difficult Tracheal Intubation in Obese Gastric Bypass Patients.
PMID- 27510590
TI - Beneficial Effects of Bariatric Surgery on Cardiac Structure and Function in
Obesity.
AB - BACKGROUND: Bariatric surgery is being considered as a therapeutic option for
morbidly obese patients. Data are accumulating showing that this surgical
intervention may improve in major cardiovascular morbidity and mortality. We
evaluated the effects of bariatric surgery on left ventricular (LV) structure and
function including LV mechanics in obese patients. METHODS: Thirty-seven patients
(age = 36 +/- 10 years; male:female = 11:26) undergoing bariatric surgery were
enrolled. Echocardiography was performed before and after at least 1 year of
bariatric surgery. Conventional echocardiographic parameters, including tissue
Doppler measurements, were measured. LV global longitudinal, circumferential, and
radial deformations were assessed utilizing 2D speckle tracking software.
RESULTS: Patients decreased body mass index by 11.8 +/- 4.7 over 15.6 +/- 5.5
months. Bariatric surgery led to significant decreases in left ventricular (LV)
size and mass (51.0 +/- 3.3 to 49.1 +/- 3.4 mm, p < 0.001 for LV end-diastolic
dimension; 192.6 +/- 33.5 to 146.2 +/- 29.1 g, p < 0.001 for LV mass), and
increases were noted in the ratio of early-to-late diastolic mitral inflow (E/A),
early diastolic tissue Doppler velocity (Em), and LV longitudinal strain (1.42 +/
0.52 to 1.59 +/- 0.56, p = 0.04 for E/A ratio; 9.7 +/- 2.0 to 11.0 +/- 2.4 cm/s,
p < 0.001 for Em; 14.1 +/- 1.9 to 16.2 +/- 1.4 %, p < 0.001 for longitudinal
strain). Changes of LV longitudinal strain were related to LV mass reduction (p =
0.04). However, LV ejection fraction, LV circumferential, and radial strains were
all comparable at follow-up. CONCLUSION: Significant weight loss by bariatric
surgery was associated with improved LV structure and function in obese patients,
suggesting potential favorable effects of bariatric surgery to prevent future
cardiovascular events.
PMID- 27510592
TI - Uniform Li2S precipitation on N,O-codoped porous hollow carbon fibers for high
energy-density lithium-sulfur batteries with superior stability.
AB - A lithium-polysulfide cell with superior stability is reported with N,O-codoped
carbon hollow fiber (NCHF) sheets as a current collector. Due to the highly
effective chemisorption and physical adsorption of lithium polysulfides on doped
NCHF and a uniform Li2S precipitation during cycling, the Li2S6-impregnated NCHF
electrodes exhibit high sulfur utilization and superior cycling stability even
with a high areal sulfur loading of 6.2 mg cm(-2).
PMID- 27510591
TI - Risk factors for Clostridium difficile infection in hemato-oncological patients:
A case control study in 144 patients.
AB - Evidence on risk factors for Clostridium difficile infection (CDI) in hemato
oncologic patients is conflicting. We studied risk factors for CDI in a large,
well-characterized cohort of hemato-oncological patients. 144 hemato-oncological
patients were identified in this retrospective, single center study with a
microbiologically confirmed CDI-associated diarrhea. Patients were compared with
144 age and sex matched hemato-oncologic patients with CDI negative diarrhea.
Risk factors such as prior antimicrobial therapy, type of disease, chemotherapy
and survival were evaluated. CDI-positive patients received more frequently any
antimicrobial agent and antimicrobial combination therapy than CDI-negative
patients (79% vs. 67%; OR = 2.26, p = 0.038 and OR = 2.62, p = 0.003,
respectively). CDI positive patients were treated more frequently with
antimicrobial agents active against C. difficile than CDI negative ones (25% vs.
13%; OR = 2.2, p = 0.039). The interval between last chemotherapy and onset of
diarrhea was significantly shorter in patients without CDI (median, 17 days vs 36
days; p < 0.001). Our study demonstrates that chemotherapy is not a significant
risk factor for CDI but for early onset CDI negative diarrhea. The predominant
modifiable risk factor for CDI is in hemato-oncological patients antimicrobial
treatment. These findings should be taken into account in the daily clinical
practice to avoid CDI associated complications and excess health care costs.
PMID- 27510593
TI - [Not Available].
PMID- 27510594
TI - A Case of Intraparenchymal Pseudoaneurysms in Kidney Allograft.
AB - BACKGROUND Percutaneous needle biopsy is routinely performed for renal allograft
management. Vascular complications of the procedure include pseudoaneurysm and
arterio-venous fistulae formation. Delayed diagnosis of these complications is
due to their mostly asymptomatic and indolent nature. CASE REPORT We present a
case of extensive intraparenchymal pseudoaneurysm formation within the inferior
pole of the allograft, diagnosed two years following the most recent biopsy
procedure. CONCLUSIONS Renal pseudoaneurysms may only be diagnosed years after
their formation as they are typically asymptomatic.
PMID- 27510595
TI - Safety and efficacy of beclomethasone dipropionate delivered by breath-actuated
or metered-dose inhaler for persistent asthma.
AB - BACKGROUND: Breath-actuated inhalers (BAI) have been developed to simplify the
delivery of inhaled medication. OBJECTIVE: To evaluate the safety and efficacy of
beclomethasone dipropionate hydrofluoroalkane BAI and metered-dose inhaler (MDI)
versus placebo in patients who previously used a mid- to high-dose inhaled
corticosteroid or inhaled corticosteroid/long-acting beta agonist for persistent
asthma. METHODS: This phase III study included five treatment groups: placebo,
and four beclomethasone dipropionate groups (BAI 320 MUg/day, BAI 640 MUg/day,
MDI 320 MUg/day, and MDI 640 MUg/day). Efficacy over 12 weeks was assessed by
spirometry, peak flow measurements, and other clinical end points. Safety was
assessed by adverse events. RESULTS: Baseline-adjusted trough morning forced
expiratory volume in 1 second area under the effect curve from time 0 to 12 weeks
(primary end point) was increased in the BAI 320 and BAI 640 MUg/day groups and
the MDI 640 MUg/day group versus placebo (not significant). Clinically important
improvements were noted in morning and evening peak expiratory flow and decreased
rescue medications. More patients who received placebo than patients in active
treatment groups withdrew due to meeting the stopping criteria for worsening
asthma. Patients in the active treatment groups experienced a greater decrease in
asthma symptoms than patients in the placebo group. Quality of life and Asthma
Control Test scores improved in the active treatment groups compared with the
placebo group (p <= 0.0074). The most common adverse events (>5% in any group)
were oral candidiasis and upper respiratory tract infection. CONCLUSION: Clinical
benefits for patients who used BAI 320 and 640 MUg/day and MDI 640 MUg/day were
demonstrated. The safety profiles of BAI 320 and 640 MUg/day were comparable with
that of the MDI. These benefits and the continued need for better symptom control
among patients with asthma support the continued development of this controller
medication. ClinicalTrials.gov identifier NCT02031640.
PMID- 27510596
TI - Antibiotic resistance: a physicist's view.
AB - The problem of antibiotic resistance poses challenges across many disciplines.
One such challenge is to understand the fundamental science of how antibiotics
work, and how resistance to them can emerge. This is an area where physicists can
make important contributions. Here, we highlight cases where this is already
happening, and suggest directions for further physics involvement in
antimicrobial research.
PMID- 27510597
TI - Freestanding Boron Nitride Nanosheet Films for Ultrafast Oil/Water Separation.
AB - Freestanding boron nitride nanosheet (BNNS) films with designed structures are
first fabricated by chemical vapor deposition (CVD) methods. As-prepared
freestanding BNNS films exhibit outstanding hydrophobicity and lipophilicity
properties. Such brilliant behaviors make them applicable in oil/water separation
with very high fluxes up to 1 200 000 L m-2 h-1 bar-1 and excellent separation
efficiencies (ppm level in terms of the water content in the filtrate).
PMID- 27510598
TI - Gestational diabetes in the United States: temporal changes in prevalence rates
between 1979 and 2010.
AB - OBJECTIVE: To examine age-period-cohort effects on trends in gestational diabetes
mellitus (GDM) prevalence in the US, and to evaluate how these trends have
affected the rates of stillbirth and large for gestational age (LGA)/macrosomia.
DESIGN: Retrospective cohort study. SETTING: USA, 1979-2010. POPULATION: Over 125
million pregnancies (3 337 284 GDM cases) associated with hospitalisations.
METHODS: Trends in GDM prevalence were examined via weighted Poisson models to
parse out the extent to which GDM trends can be attributed to maternal age,
period of delivery, and maternal birth cohort. Multilevel models were used to
assess the contribution of population effects to the rate of GDM. Log-linear
Poisson regression models were used to estimate the contributions of the
increasing GDM rates to changes in the rates of LGA and stillbirth between 1979
81 and 2008-10. MAIN OUTCOME MEASURES: Rates and rate ratios (RRs). RESULTS:
Compared with 1979-1980 (0.3%), the rate of GDM has increased to 5.8% in 2008-10,
indicating a strong period effect. Substantial age and modest cohort effects were
evident. The period effect is partly explained by period trends in body mass
index (BMI), race, and maternal smoking. The increasing prevalence of GDM is
associated with a 184% (95% CI 180-188%) decline in the rate of LGA/macrosomia
and a 0.75% (95% CI 0.74-0.76) increase in the rate of stillbirths for 2008-10,
compared with 1979-81. CONCLUSIONS: The temporal increase in GDM can be
attributed to period of pregnancy and age. Increasing BMI appears to partially
contribute to the GDM increase in the US. TWEETABLE ABSTRACT: The increasing
prevalence of GDM can be attributed to period of delivery and increasing maternal
age.
PMID- 27510599
TI - Reinstating the Novelty P3.
AB - P300 (or P3) is a major positive complex in the human event-related potential,
occurring some 300 ms after stimulus onset, and long thought to be the cortical
correlate of the Orienting Reflex, our automatic attention-grabbing response to a
novel stimulus. The Novelty P3 was the third P3 subcomponent discovered (after
P3a and P3b) and appeared promising in its sensitivity to stimulus novelty, the
defining characteristic of the Orienting Reflex. But some 15 years later it was
claimed to be indistinguishable from the previously-discovered P3a. This led to a
decline in interest in the field and confused nomenclature, with some studies
using "P3a" and "Novelty P3" interchangeably. However, recent similar studies
have again reported three subcomponents of the P3. Further, using single-stimulus
habituation paradigms, in addition to P3a and P3b, a later decrementing P3
subcomponent has been reported, and recently labelled "HabP3" to avoid
contention. We report three studies to resolve this chaotic situation, arguing
for identification of the late subcomponent following the P3a and P3b as the
Novelty P3. Reinstatement of the Novelty P3 as the central index of the Orienting
Reflex will have widespread impact in a range of theoretical, practical, and
clinical areas involving novelty processing and attention.
PMID- 27510600
TI - Association between shortened telomere length and systemic lupus erythematosus: a
meta-analysis.
AB - Objective We aimed to evaluate the relationship between telomere length and
systemic lupus erythematosus (SLE). Methods PUBMED and EMBASE databases were
searched; meta-analyses were performed comparing telomere length in SLE patients
and healthy controls, and on SLE patients in subgroups based on ethnicity, sample
type, assay method and data type. Results Eight studies including 472 SLE
patients and 365 controls were ultimately selected which showed that telomere
length was significantly shorter in the SLE group than in the control group
(standardized mean difference (SMD) = -0.835, 95% confidence interval (CI) =
1.291 to -0.380, p = 3.3 * 10-4). Stratification by ethnicity showed
significantly shortened telomere length in the SLE group in Caucasian, Asian and
mixed populations (SMD = -0.455, 95% CI = -0.763 to -0.147, p = 0.004; SMD =
0.887, 95% CI = -1.261 to -0.513, p = 3.4 * 10-4; SMD = -0.535, 95% CI = -0.923
to -0.147, p = 0.007; respectively). Furthermore, telomere length was
significantly shorter in the SLE group than in the control group in whole blood
and peripheral blood mononuclear cell groups (SMD = -0.361, 95% CI = -0.553 to
0.169, p = 2.3 * 10-4; SMD = -1.546, 95% CI = -2.583 to -0.510, p = 0.003;
respectively); a similar trend was observed in leukocyte groups (SMD = -0.699,
95% CI = -1.511 to -0.114, p = 0.092). Meta-analyses based on assay method or
data type revealed similar associations. Conclusions Our meta-analysis
demonstrated that telomere length was significantly shorter in patients with SLE,
regardless of ethnicity, sample type or assay method evaluated.
PMID- 27510601
TI - Association between antiphospholipid antibodies and arterial thrombosis in
patients with rheumatoid arthritis.
AB - OBJECTIVES: Antiphospholipid antibodies (aPL) are present in a proportion of
patients with rheumatoid arthritis but their clinical significance remains
unclear. We investigated the association between aPL and thrombotic events in
rheumatoid arthritis patients. METHODS: In this cross-sectional study, aPL
profiles were evaluated in 376 rheumatoid arthritis patients in accordance with
the standard guidelines. Clinical and radiographic data were retrospectively
collected. RESULTS: aPL were identified in 39 patients (10.4%). Lupus
anticoagulant was the most common subtype (n = 25, 6.6%); anti-cardiolipin
antibodies and anti-beta2 glycoprotein I antibodies were detected in six and 12
patients (1.6% and 3.2%), respectively. Compared to the aPL-negative group, aPL
positive patients included more male patients (41.0% vs. 15.4%, P < 0.001) and
more smokers (41.0% vs. 16.0%, P = 0.001). There was no difference between the
two groups in age, disease duration and body mass index, or the frequency of
diabetes, hypertension or dyslipidaemia. Of note, arterial thromboses were more
common in the aPL-positive than the aPL-negative group (12.8% vs. 2.1%, P =
0.004), whereas the frequency of venous thrombosis did not differ between the two
groups (0.0% vs. 0.9%, P = 1.000). On multivariate regression analysis, aPL, age,
hypertension, dyslipidaemia and baseline C-reactive protein level were
independently associated with arterial thrombotic events (all P values < 0.05).
CONCLUSION: aPL was found in a subset of rheumatoid arthritis patients, who were
more often smokers, and aPL was independently associated with development of
arterial thrombosis. This result suggests that aPL may contribute to an increased
risk of arterial thrombosis in rheumatoid arthritis patients.
PMID- 27510602
TI - Short-term atorvastatin therapy improves arterial stiffness of middle-aged
systemic lupus erythematosus patients with pathological pulse wave velocity.
AB - Objectives Statins have been proposed as a potential treatment for systemic lupus
erythematosus (SLE) due to their immunomodulatory properties, their role
restoring endothelial function and preventing atherosclerosis. We evaluate the
effect of a short period treatment with a low dose of atorvastatin and its
withdrawal on early stage subclinical atherosclerosis. Methods Thirty-seven SLE
females received 20 mg/day atorvastatin during eight weeks. At baseline, at the
end of treatment and six months after atorvastatin withdrawal, disease activity,
subclinical atherosclerosis -assessed by measuring carotid-femoral pulse wave
velocity (PWV) - and quantification of circulating endothelial progenitor cells
(EPC) - as a surrogate biological marker of subclinical atherosclerosis - were
carried out. Results The group of SLE patients with baseline pathological
arterial stiffness showed a significant decrease of PWV after atorvastatin
therapy (8.43 +/- 1.45 m/s vs 7.42 +/- 1.06 m/s; p = 0.002) that is maintained
six months after treatment finished. Only patients of the middle-aged group
showed a nearly significant decrease in the PWV measured along the study (7.16 +/
1.23 m/s vs 6.76 +/- 0.82 m/s; p = 0.05). Atorvastatin induced a significant
decrease in the circulating EPC percentage (0.65 +/- 0.67 vs 0.40 +/- 0.31; p =
0.023) as well as a downward trend of disease activity that it is observed by a
decrease in SLE disease activity index simultaneously with an increase in C3
complement and significant decrease in serum concentration of vascular
endothelial grow factor (VEGF) and sVCAM-1. Conclusions Short-term atorvastatin
therapy reduces arterial stiffness of SLE patients with baseline pathological
PWV, who are mainly in the group of middle-aged patients. Further studies are
needed to determine whether these patients would benefit from statin therapy in
preventing cardiovascular events.
PMID- 27510603
TI - Clinical characteristics of children with membranous lupus nephritis: the
Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.
AB - Objective The objective of this article is to describe and compare clinical
features, treatment, and renal outcomes of children with membranous lupus
nephritis (MLN), through analysis of a national multicenter registry. Methods
Patients with pediatric systemic lupus erythematosus (SLE) and MLN from the
Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry
were included. Demographic, disease and medication-related data were collected
between 2010 and 2014 from 59 CARRA Legacy Registry sites. Results A total of 132
individuals had MLN, either in isolation or in combination with proliferative LN.
Seventy-four patients had pure MLN. The proportion of patients with daily
corticosteroid treatment was similar among groups (96%, 91%, and 96%, for class
III+V, IV+V, and V, respectively, p = 0.67). Proportion of individuals exposed to
any disease-modifying antirheumatic drug (DMARD) or biologic was similar among
the three groups (83%, 91%, 95% for class III+V, IV+V, and V, respectively, p =
0.189). Proportion of patients with decreased glomerular filtration rate (less
than 90 ml/min/1.73 m2) was significantly different among groups (4%, 38%, and
4%, for class III+V, IV+V, and V, respectively, p < 0.0001). Conclusion This is
the largest reported cohort of children with MLN. More research is needed to
understand treatment practices for pediatric MLN, particularly decisions related
to pharmacologic treatment of pure MLN. More work is also needed to identify
prognostic factors and predictors of outcome for pediatric MLN. Future
observational studies will be a first step toward understanding and formulating a
standardized approach to treatment of pediatric membranous LN and allowing for
the initiation of prospective comparative effectiveness studies and
interventional trials.
PMID- 27510604
TI - Rapidly progressive lupus nephritis associated with golimumab in a patient with
systemic lupus erythematosus and rheumatoid arthritis.
PMID- 27510605
TI - Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for
the diagnosis of antiphospholipid syndrome: results of an international
multicentre study.
AB - Objective A task force of scientists at the International Congress on
Antiphospholipid Antibodies recognized that phosphatidylserine-dependent
antiprothrombin antibodies (aPS/PT) might contribute to a better identification
of antiphospholipid syndrome (APS). Accordingly, initial and replication
retrospective, cross-sectional multicentre studies were conducted to ascertain
the value of aPS/PT for APS diagnosis. Methods In the initial study (eight
centres, seven countries), clinical/laboratory data were retrospectively
collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics
(Inova) using two ELISA kits. A replication study (five centres, five countries)
was carried out afterwards. Results In the initial study ( n = 247), a moderate
agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed ( k =
0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those
without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity,
positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS
diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study ( n
= 214), a moderate/substantial agreement between the IgG aPS/PT results obtained
with both ELISA kits was observed ( k = 0.630). IgG aPS/PT were more prevalent in
APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p <
0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%,
3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily
performed laboratory parameter that might contribute to a better and more
complete identification of patients with APS.
PMID- 27510607
TI - Chameleonic electrochemical metallization cells: dual-layer solid electrolyte
inducing various switching behaviours.
AB - We present 'unusual' resistive switching behaviours in electrochemical
metallization (ECM) cells utilizing a dual-layer (SiOx/GeSex: SiOx on GeSex)
solid electrolyte (SE). The observed switching behaviour markedly varies with the
thickness of the upper SiOx layer and compliance current: (i) monostable
switching, (ii) counter-eightwise bipolar switching, and (iii) combination of
monostable and eightwise bipolar switching behaviours. Focusing on cases (i) and
(iii), electrical and chemical analyses on these chameleonic cells were performed
in an attempt to gain clues to the understanding of the observed complexity. The
chemical analysis indicated the upper SiOx layer as a chemical potential well for
Cu ions-Cu ions were largely confined in the well. This non-uniform distribution
of Cu across the SE perhaps hints at the mechanism for the complex behaviour; it
may be a 'zero-sum game' between SiOx and GeSex layers, in which the two layers
fight over the limited number of Cu atoms/ions.
PMID- 27510608
TI - Intrusive Thoughts, Impulses, and Schizoaffective Disorder.
PMID- 27510606
TI - A reverse genetic approach identifies an ancestral frameshift mutation in RP1
causing recessive progressive retinal degeneration in European cattle breeds.
AB - BACKGROUND: Domestication and artificial selection have resulted in strong
genetic drift, relaxation of purifying selection and accumulation of deleterious
mutations. As a consequence, bovine breeds experience regular outbreaks of
recessive genetic defects which might represent only the tip of the iceberg since
their detection depends on the observation of affected animals with distinctive
symptoms. Thus, recessive mutations resulting in embryonic mortality or in non
specific symptoms are likely to be missed. The increasing availability of whole
genome sequences has opened new research avenues such as reverse genetics for
their investigation. Our aim was to characterize the genetic load of 15 European
breeds using data from the 1000 bull genomes consortium and prove that widespread
harmful mutations remain to be detected. RESULTS: We listed 2489 putative
deleterious variants (in 1923 genes) segregating at a minimal frequency of 5 % in
at least one of the breeds studied. Gene enrichment analysis showed major
enrichment for genes related to nervous, visual and auditory systems, and
moderate enrichment for genes related to cardiovascular and musculoskeletal
systems. For verification purposes, we investigated the phenotypic consequences
of a frameshift variant in the retinitis pigmentosa-1 gene segregating in several
breeds and at a high frequency (27 %) in Normande cattle. As described in certain
human patients, clinical and histological examination revealed that this mutation
causes progressive degeneration of photoreceptors leading to complete blindness
in homozygotes. We established that the deleterious allele was even more frequent
in the Normande breed before 1975 (>40 %) and has been progressively counter
selected likely because of its associated negative effect on udder morphology.
Finally, using identity-by-descent analysis we demonstrated that this mutation
resulted from a unique ancestral event that dates back to ~2800 to 4000 years.
CONCLUSIONS: We provide a list of mutations that likely represent a substantial
part of the genetic load of domestication in European cattle. We demonstrate that
they accumulated non-randomly and that genes related to cognition and sensory
functions are particularly affected. Finally, we describe an ancestral
deleterious variant segregating in different breeds causing progressive retinal
degeneration and irreversible blindness in adult animals.
PMID- 27510609
TI - Genetic education, knowledge and experiences between nurses and physicians in
primary care in Brazil: A cross-sectional study.
AB - Recent advances in genomics and related technologies have the potential to
improve health care throughout the world. In this cross-sectional study, we
examine genetics education, knowledge, and genetics-related experiences among the
nurses and physicians who provide primary care in a Brazilian city. Fifty-four
healthcare professionals from family health units participated in the study
(response rate: 90%). Data were collected using a structured 36-item
questionnaire divided into five axes: sociodemographic data and academic
background; genetics education; genetics knowledge; genetics-related experiences
in family practice; and knowledge regarding the National Policy for Comprehensive
Care in Clinical Genetics in the Unified Health System. Although most
participants (85.2%) acknowledged receiving some genetic content during their
undergraduate education, the majority (77.8%) advised that they did not feel
prepared to deliver genomics-based health care in primary care. The results
suggest that nurses and physicians often lack the knowledge to provide genomics
based health care in primary care. Therefore, continuing education in
genetics/genomics should be provided to primary healthcare professionals in order
to enhance family practice and compliance with national policies.
PMID- 27510610
TI - Iodinated (Perfluoro)alkyl Quinoxalines by Atom Transfer Radical Addition Using
ortho-Diisocyanoarenes as Radical Acceptors.
AB - A simple method for the preparation of functionalized quinoxalines is reported.
Starting from readily accessible ortho-diisocyanoarenes and (perfluoro)alkyl
iodides, the quinoxaline core is constructed during (perfluoro)alkylation by atom
transfer radical addition (ATRA), resulting in 2-iodo-3
(perfluoro)alkylquinoxalines. The radical cascades are readily initiated either
with visible light or by using alpha,alpha'-azobisisobutyronitrile (AIBN). The
heteroarene products are obtained in high yields (up to 94 %), and the method can
be readily scaled up. Useful follow-up chemistry documents the value of the novel
radical quinoxaline synthesis.
PMID- 27510611
TI - Bacteria Delay the Jamming of Particles at Microchannel Bottlenecks.
AB - Clogging of channels by complex systems such as mixtures of colloidal and
biological particles is commonly encountered in different applications. In this
work, we analyze and compare the clogging mechanisms and dynamics by pure and
mixture suspensions of polystyrene latex particles and Escherichia coli by
coupling fluorescent microscopic observation and dynamic permeability
measurements in microfluidic filters. Pure particles filtration leads to arches
and deposit formation in the upstream side of the microfilter while pure bacteria
form streamers in the downstream zone. When mixing particle and bacteria, an
unexpected phenomenon occurs: the clogging dynamics is significantly delayed.
This phenomenon is related to apparent "slippery" interactions between the
particles and the bacteria. These interactions limit the arches formation at the
channels entrances and favour the formation of dendritic structures on the
pillars between the channels. When these dendrites are eroded by the flow,
fragments of the deposit are dragged towards the channels entrances. However,
these bacteria/particles clusters being lubricated by the slippery interactions
are deformed and stretched by the shear thus facilitating their passage through
the microchannels.
PMID- 27510612
TI - Pediatrics in 21st Century and Beyond.
AB - Pediatrics is a dynamic discipline and there is awareness and hope for
actualizing outstanding achievements in the field of child health in 21st century
and beyond. Improved lifestyle and quality of children's health is likely to
reduce the burden of adult diseases and enhance longevity because seeds of most
adult diseases are sown in childhood. Identification and decoding of human genome
is expected to revolutionize the practice of pediatrics. The day is not far off
when a patient will walk into doctor's chamber with an electronic or digital
health history on a CD or palmtop and a decoded genomic constitution. There will
be reduced burden of genetic diseases because of selective abortions of
"defective" fetuses and replacement of "bad" genes with "good" ones by genetic
engineering. Availability of totipotent stem cells and developments in transplant
technology are likely to revolutionize the management of a variety of hematologic
cancers and life-threatening genetic disorders. The possibility of producing
flawless designer babies by advances in assisted reproductive technologies (ARTs)
is likely to be mired by several ethical and legal issues.The availability of
newer vaccines by recombinant technology for emerging infective and for non
infective lifestyle diseases is likely to improve survival and quality of life.
There is going to be a greater focus on the "patient" having the disease rather
than "disease" per se by practicing holistic pediatrics by effective utilization
of alternative or complementary strategies for health care. Due to advances in
technology, pediatrics may get further dehumanized. A true healer cannot simply
rely on technology; there must be a spiritual bond between the patient and the
physician by exploiting the concept of psycho-neuro-immunology and body-mind
interactions. In the years to come, physicians are likely to play "god" but
medicine can't achieve immortality because anything born must die in accordance
with nature's recycling blueprint. The medical science is likely to improve
longevity but our goal should be to improve the quality of life.
PMID- 27510613
TI - Editorial: New Horizons in Genetic Diagnosis in Pediatric Practice: The
Excitement and Challenges!
PMID- 27510614
TI - Morphometric analysis of endometrial cells in liquid-based cervical cytology
samples.
AB - BACKGROUND: Exfoliated endometrial cells can be seen in cervical smears in
association with a wide variety of conditions ranging from normal proliferative
endometrium to endometrial malignancies. It is often difficult to differentiate
between benign, atypical and malignant endometrial cells using cytomorphology
alone. This study was conducted to evaluate if morphometric analysis of
endometrial nuclei on liquid-based cervical samples could be of help in
differentiating between these endometrial cells. MATERIALS AND METHODS: Three
groups of cervical samples with histopathological correlation were selected:
Group A: showing benign endometrial cells; Group B: showing atypical endometrial
cells and Group C: showing malignant endometrial cells. There were 30 cases each
in Group A and B and 39 cases in Group C. Image J, NIH, USA was used for
selecting the endometrial nuclei and performing the morphometric measurements.
MANOVA was used for statistical analysis. RESULTS: The mean nuclear area and
nuclear perimeter were significantly different between the three groups of
endometrial cells with a P-value <0.05. However, the mean standard deviation of
the nuclear area (SDNA) was not significantly different between atypical and
malignant endometrial cells (P = 0.765) and the mean nuclear diameter was not
statistically different between benign and atypical cells (P = 0.112). Also, the
difference in the mean integrated gray density amongst all three groups was not
statistically significant (P = 0.397, 0.844, 0.732). CONCLUSION: We conclude that
the morphometric parameters of the nuclear area and nuclear perimeter are helpful
in differentiating between benign, atypical and malignant endometrial nuclei even
in liquid-based cervical cytology samples.
PMID- 27510617
TI - Most patients taking warfarin do not maintain stable INR values.
PMID- 27510615
TI - An Algorithm for Neuropathic Pain Management in Older People.
AB - Neuropathic pain frequently affects older people, who generally also have several
comorbidities. Elderly patients are often poly-medicated, which increases the
risk of drug-drug interactions. These patients, especially those with cognitive
problems, may also have restricted communication skills, making pain evaluation
difficult and pain treatment challenging. Clinicians and other healthcare
providers need a decisional algorithm to optimize the recognition and management
of neuropathic pain. We present a decisional algorithm developed by a
multidisciplinary group of experts, which focuses on pain assessment and
therapeutic options for the management of neuropathic pain, particularly in the
elderly. The algorithm involves four main steps: (1) detection, (2) evaluation,
(3) treatment, and (4) re-evaluation. The detection of neuropathic pain is an
essential step in ensuring successful management. The extent of the impact of the
neuropathic pain is then assessed, generally with self-report scales, except in
patients with communication difficulties who can be assessed using behavioral
scales. The management of neuropathic pain frequently requires combination
treatments, and recommended treatments should be prescribed with caution in these
elderly patients, taking into consideration their comorbidities and potential
drug-drug interactions and adverse events. This algorithm can be used in the
management of neuropathic pain in the elderly to ensure timely and adequate
treatment by a multidisciplinary team.
PMID- 27510616
TI - FSH aggravates bone loss in ovariectomised rats with experimental periapical
periodontitis.
AB - Periapical bone loss is one of the prominent pathological and clinical features
of periapical periodontitis. Previous studies have demonstrated that follicle
stimulating hormone (FSH) could directly affect skeletal remodelling by
stimulating the formation and the function of osteoclasts in vitro and in vivo.
However, the effect of FSH on periapical bone loss remained to be fully
elucidated. In the current study, a rat model was established in order to verify
the effect of FSH in experimental periapical lesions. It was identified that FSH
aggravated the bone loss of periapical lesions. In addition, RANKL-, TRAP-, TNF
alpha- and IL-1beta-positive cells were increased significantly in FSH-treated
groups, which indicated that the function of FSH in bone loss may be mediated
through the increasing activity of osteoclasts and the increased secretion of
inflammatory cytokines. The results of the current study suggested that FSH,
independent of oestrogen, may aggravate periapical bone loss by FSH receptors,
which may serve an important role in the immune and inflammatory response of the
host to root canal and periradicular infection during menopause.
PMID- 27510618
TI - Post-exercise heart-rate recovery correlates to resting heart-rate variability in
healthy men.
AB - JUSTIFICATIVE: The relationship between post-exercise heart-rate recovery (HRR)
and resting cardiac autonomic modulation is an incompletely explored issue.
OBJECTIVE: To correlate HRR with resting supine and orthostatic autonomic status.
METHOD: HRR at the 1st, 3th, and 5th min following maximal treadmill exercise
were correlated with 5-min time-domain (CV, pNN50 and rMSSD) and frequency-domain
(TP, LF, HF, LFn, HFn, and LF/HF ratio) indices of heart-rate variability (HRV)
in both supine and standing positions in 31 healthy physically active non
athletes men. Statistical analysis employed non-parametric tests with two-tailed
p value set at 5 %. RESULTS: Absolute HRR and Delta %HRR at each post-exercise
time did not correlated with HRV in supine position, as well as at 1st min in
standing position. At the 3rd min and 5th min, these measures negatively
correlated with pNN50, rMSSD, TP, and HF indices, and only in the 5th min, they
showed negative correlation with HFn and positive correlation with LF, LFn, and
LF/HF ratio in the standing position. Coefficient of HRR (CHRR) at the 1st min
negatively correlated with pNN50 and rMSSD and at 3rd and 5th min showed positive
correlation with LFn and LF/HF ratio in supine position. With HRV indices in
standing position CHRR from the 1st to 5th min showed the same respective
negative and positive correlations as the other measures. CONCLUSION: HRR from
the 1st to 5th min post-exercise negatively correlated with parasympathetic
modulation in resting orthostatic, but showed no correlation in supine position.
At the 3rd and 5th min, a positive correlation with combined sympathetic
parasympathetic modulation in both positions was observed.
PMID- 27510619
TI - Advancing Risk Analysis for Nanoscale Materials: Report from an International
Workshop on the Role of Alternative Testing Strategies for Advancement.
AB - The Society for Risk Analysis (SRA) has a history of bringing thought leadership
to topics of emerging risk. In September 2014, the SRA Emerging Nanoscale
Materials Specialty Group convened an international workshop to examine the use
of alternative testing strategies (ATS) for manufactured nanomaterials (NM) from
a risk analysis perspective. Experts in NM environmental health and safety, human
health, ecotoxicology, regulatory compliance, risk analysis, and ATS evaluated
and discussed the state of the science for in vitro and other alternatives to
traditional toxicology testing for NM. Based on this review, experts recommended
immediate and near-term actions that would advance ATS use in NM risk assessment.
Three focal areas-human health, ecological health, and exposure considerations
shaped deliberations about information needs, priorities, and the next steps
required to increase confidence in and use of ATS in NM risk assessment. The
deliberations revealed that ATS are now being used for screening, and that, in
the near term, ATS could be developed for use in read-across or categorization
decision making within certain regulatory frameworks. Participants recognized
that leadership is required from within the scientific community to address basic
challenges, including standardizing materials, protocols, techniques and
reporting, and designing experiments relevant to real-world conditions, as well
as coordination and sharing of large-scale collaborations and data. Experts
agreed that it will be critical to include experimental parameters that can
support the development of adverse outcome pathways. Numerous other insightful
ideas for investment in ATS emerged throughout the discussions and are further
highlighted in this article.
PMID- 27510620
TI - Seasonal effects on plasma cortisol concentrations in the Bedouin buck: circadian
studies and response to ACTH.
AB - Our work aims at the exploration of cortisol secretion in the Bedouin goat,
native to the Algerian Sahara desert, to understand the mechanisms of adaptation
to extreme hot climates. In the present study, diurnal and seasonal variations of
cortisol concentrations were measured in basal conditions, as well as the
response to ACTH stimulation tests across seasons in bucks. The plasma
concentrations of cortisol showed no diurnal cycle but a large variation across
seasons. The highest levels occurred in summer and winter when the environmental
conditions are at their extreme levels. The rectal temperature showed
nychthemeral and seasonal variations, and BW was also different across seasons
with highest values in summer and lowest in winter. The results obtained after
administration of two doses (2 or 10 MUg/kg BW) of synthetic ACTH to three
different age groups (kids, adults and elderly animals) showed a strong increase
in plasma cortisol concentrations under all conditions with maximum levels
achieved between 15 and 120 min. The analysis of the area under the cortisol
curve showed no significant difference between the responses to the two doses of
ACTH and between age groups, but showed seasonal variations with the lowest
response in autumn than in other seasons. We conclude that season significantly
affects secretion of cortisol in both basal state and under ACTH stimulation.
However, the variation of adrenal reactivity to ACTH is not sufficient to explain
seasonal differences, and in particular the summer peak in basal circulating
cortisol concentrations. Further research should focus on the respective
contribution of environmental factors (such as day length, temperature, humidity)
and the mechanisms involved in cortisol regulation.
PMID- 27510621
TI - Commentary: Theoretical and Methodological Dimensions of Convergence and
Divergence of Adolescent and Parent Reports about Youth Development and Family
Structure and Function-A Relational Developmental Systems Perspective.
AB - Using ideas associated with relational developmental systems metatheory, we
discuss the links among the operation triad model of adolescent report-parent
report convergence, divergence, or compensation and the research reported in this
special issue. These contributions highlight the important implications for
adolescent adjustment of youth and parent reports about adolescent development
and family structure and function. Relational developmental systems metatheory
raises both theoretical and methodological issues for research framed by the
operation triad model. These issues emphasize the specificity (non-ergodicity) of
mutually influential relationships between a youth and his/her parent, that is,
the specificity of the adolescent-parent relationship. Relational developmental
systems -based ideas may enable the operation triad model to be a means through
which the study of adolescent self-reports and parent reports will have a more
central place in the construction of key features of the dynamics of adolescent
parent relationships.
PMID- 27510622
TI - Potassium channels in the Cx43 gap junction perinexus modulate ephaptic coupling:
an experimental and modeling study.
AB - It was recently demonstrated that cardiac sodium channels (Nav1.5) localized at
the perinexus, an intercalated disc (ID) nanodomain associated with gap junctions
(GJ), may contribute to electrical coupling between cardiac myocytes via an
ephaptic mechanism. Impairment of ephaptic coupling by acute interstitial edema
(AIE)-induced swelling of the perinexus was associated with arrhythmogenic,
anisotropic conduction slowing. Given that Kir2.1 has also recently been reported
to localize at intercalated discs, we hypothesized that Kir2.1 channels may
reside within the perinexus and that inhibiting them may mitigate arrhythmogenic
conduction slowing observed during AIE. Using gated stimulated emission depletion
(gSTED) and stochastic optical reconstruction microscopy (STORM) super-resolution
microscopy, we indeed find that a significant proportion of Kir2.1 channels
resides within the perinexus. Moreover, whereas Nav1.5 inhibition during AIE
exacerbated arrhythmogenic conduction slowing, inhibiting Kir2.1 channels during
AIE preferentially increased transverse conduction velocity-decreasing anisotropy
and ameliorating arrhythmia risk compared to AIE alone. Comparison of our results
with a nanodomain computer model identified enrichment of both Nav1.5 and Kir2.1
at intercalated discs as key factors underlying the experimental observations. We
demonstrate that Kir2.1 channels are localized within the perinexus alongside
Nav1.5 channels. Further, targeting Kir2.1 modulates intercellular coupling
between cardiac myocytes, anisotropy of conduction, and arrhythmia propensity in
a manner consistent with a role for ephaptic coupling in cardiac conduction. For
over half a century, electrical excitation in the heart has been thought to occur
exclusively via gap junction-mediated ionic current flow between cells. Further,
excitation was thought to depend almost exclusively on sodium channels with
potassium channels being involved mainly in returning the cell to rest. Here, we
demonstrate that sodium and potassium channels co-reside within nanoscale domains
at cell-to-cell contact sites. Experimental and computer modeling results suggest
a role for these channels in electrical coupling between cardiac muscle cells via
an ephaptic mechanism working in tandem with gap junctions. This new insight into
the mechanism of cardiac electrical excitation could pave the way for novel
therapies against cardiac rhythm disturbances.
PMID- 27510623
TI - In-vivo monitoring of development of cholangiocarcinoma induced with C. sinensis
and N-nitrosodimethylamine in Syrian golen hamsters using ultrasonography and
magnetic resonance imaging: a preliminary study.
AB - OBJECTIVES: The purpose of this study is to evaluate high-resolution ultrasound
and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the
hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). MATERIALS
AND METHODS: Twenty-four male Syrian golden hamsters of were divided into four
groups composed of five hamsters as control, five hamsters receiving 30
metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in
drinking water, and nine hamsters receiving both metacercariae and NDMA.
Ultrasound was performed every other week from baseline to the 12th week of
infection. MRI and histopathologic examination was done from the 4th week to 12th
week. RESULTS: Cholangiocarcinomas appeared as early as the 6th week of
infection. There were 12 cholangiocarcinomas, nine and ten of which were
demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of
cholangiocarcinomas in the hamsters were similar to those of the mass-forming
intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other
findings of disease progression such as periductal increased echogenicity or
signal intensity, ductal dilatation, complicated cysts, and sludges in the
gallbladder. CONCLUSIONS: High-resolution ultrasound and MRI can monitor and
detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. KEY
POINTS: * High-resolution ultrasound and MRI can monitor occurrence of
cholangiocarcinoma in the hamsters. * Cholangiocarcinomas were detected as early
as the 6th week after C. sinensis infection. * Axial T2-weighted MRI demonstrated
cholangiocarcinomas and various inflammatory findings in the hamsters.
PMID- 27510624
TI - Added value of point shear-wave elastography in the diagnosis of acute
cholecystitis.
AB - OBJECTIVE: To evaluate the added value of point shear-wave elastography (pSWE) in
the diagnostic performance of conventional US for diagnosis of acute
cholecystitis. METHODS: B-mode and colour Doppler US and pSWE were performed
prospectively in 216 patients with clinically suspected acute cholecystitis. The
morphology and mural vascularity of the gallbladder and median shear wave
velocity (SWV) of the right liver were evaluated. Two observers independently
reviewed conventional US images and subsequently reviewed combined conventional
US and pSWE images. RESULTS: Mean SWVs of the acute cholecystitis group (n = 91)
were significantly higher than those of the control group (n = 85) in the right
liver within 2 cm lateral to the gallbladder (1.56 versus 1.03 m/s, 1.39 versus
1.04 m/s, P < 0.0001) with a cut-off value of 1.29 or 1.16 m/s. The area under
the receiver operating characteristic curve of both observers in the diagnosis of
acute cholecystitis improved significantly from 0.790 and 0.777 to 0.963 and
0.962, respectively, after additional review of pSWE images (P < 0.0001).
Diagnostic accuracy, sensitivity, specificity, positive and negative predictive
values of combined image sets were higher than those of conventional US images
alone. CONCLUSION: Adding pSWE to conventional US improves the diagnosis of acute
cholecystitis when compared with conventional US alone. KEY POINTS: * In acute
cholecystitis, stiffness of the right liver increases adjacent to the
gallbladder. * The cut-off value for diagnosing acute cholecystitis was 1.29 or
1.16 m/s. * Adding pSWE to conventional US improves the diagnosis of acute
cholecystitis.
PMID- 27510625
TI - Noninvasive evaluation of global and regional left ventricular function using
computed tomography and magnetic resonance imaging: a meta-analysis.
AB - OBJECTIVES: To compare the diagnostic accuracy of computed tomography (CT) in the
assessment of global and regional left ventricular (LV) function with magnetic
resonance imaging (MRI). METHODS: MEDLINE, EMBASE and ISI Web of Science were
systematically reviewed. Evaluation included: ejection fraction (EF), end
diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and left
ventricular mass (LVM). Differences between modalities were analysed using limits
of agreement (LoA). Publication bias was measured by Egger's regression test.
Heterogeneity was evaluated using Cochran's Q test and Higgins I2 statistic. In
the presence of heterogeneity the DerSimonian-Laird method was used for
estimation of heterogeneity variance. RESULTS: Fifty-three studies including
1,814 patients were identified. The mean difference between CT and MRI was -0.56
% (LoA, -11.6-10.5 %) for EF, 2.62 ml (-34.1-39.3 ml) for EDV and 1.61 ml (-22.4
25.7 ml) for ESV, 3.21 ml (-21.8-28.3 ml) for SV and 0.13 g (-28.2-28.4 g) for
LVM. CT detected wall motion abnormalities on a per-segment basis with 90 %
sensitivity and 97 % specificity. CONCLUSIONS: CT is accurate for assessing
global LV function parameters but the limits of agreement versus MRI are
moderately wide, while wall motion deficits are detected with high accuracy. KEY
POINTS: * CT helps to assess patients with coronary artery disease (CAD). * MRI
is the reference standard for evaluation of left ventricular function. * CT
provides accurate assessment of global left ventricular function.
PMID- 27510626
TI - DNA damage in lymphocytes induced by cardiac CT and comparison with physical
exposure parameters.
AB - OBJECTIVES: To investigate whether physical exposure parameters such as the dose
index (CTDI), dose length product (DLP), and size-specific dose estimate (SSDE)
are predictive of DNA damage. METHODS: In vitro, we scanned a phantom containing
blood samples from five volunteers at CTDI 50, 100, and 150 mGy. One sample was
not scanned. We also scanned samples in three different-size phantoms at CTDI 100
mGy. In vivo, we enrolled 45 patients and obtained blood samples before and after
cardiac CT. The gamma-H2AX foci were counted. RESULTS: In vitro, in the control
and at CTDI 50, 100, and 150 mGy, the number of gamma-H2AX was 0.94 +/- 0.24
(standard error, SE), 1.28 +/- 0.30, 1.91 +/- 0.47, and 2.16 +/- 0.20. At SSDE
180, 156, and 135 mGy, it was 2.41 +/- 0.20, 1.91 +/- 0.47, and 1.42 +/- 0.20
foci/cell. The gamma-H2AX foci were positively correlated with the radiation dose
and negatively correlated with the body size. In vivo, the gamma-H2AX foci were
significantly increased after CT (from 1.21 +/- 0.19 to 1.92 +/- 0.22 foci/cell)
and correlated with CTDI, DLP, and SSDE. CONCLUSIONS: DNA damage was induced by
cardiac CT. There was a correlation between the physical exposure parameters and
gamma-H2AX. KEY POINTS: * DNA damage was induced by radiation exposure from
cardiac CT. * The gamma-H2AX foci number was correlated with the CT radiation
dose. * Physical exposure parameters reflect the DNA damage by CT radiation
exposure.
PMID- 27510627
TI - Detection of pulmonary fat embolism with dual-energy CT: an experimental study in
rabbits.
AB - OBJECTIVES: To evaluate the use of dual-energy CT imaging of the lung perfused
blood volume (PBV) for the detection of pulmonary fat embolism (PFE). METHODS:
Dual-energy CT was performed in 24 rabbits before and 1 hour, 1 day, 4 days and 7
days after artificial induction of PFE via the right ear vein. CT pulmonary
angiography (CTPA) and lung PBV images were evaluated by two radiologists, who
recorded the presence, number, and location of PFE on a per-lobe basis.
Sensitivity, specificity, and accuracy of CTPA and lung PBV for detecting PFE
were calculated using histopathological evaluation as the reference standard.
RESULTS: A total of 144 lung lobes in 24 rabbits were evaluated and 70 fat emboli
were detected on histopathological analysis. The overall sensitivity, specificity
and accuracy were 25.4 %, 98.6 %, and 62.5 % for CTPA, and 82.6 %, 76.0 %, and
79.2 % for lung PBV. Higher sensitivity (p < 0.001) and accuracy (p < 0.01), but
lower specificity (p < 0.001), were found for lung PBV compared with CTPA. Dual
energy CT can detect PFE earlier than CTPA (all p < 0.01). CONCLUSION: Dual
energy CT provided higher sensitivity and accuracy in the detection of PFE as
well as earlier detection compared with conventional CTPA in this animal model
study. KEY POINTS: * Fat embolism occurs commonly in patients with traumatic bone
injury. * Dual-energy CT improves diagnostic performance for pulmonary fat
embolism detection. * Dual-energy CT can detect pulmonary fat embolism earlier
than CTPA.
PMID- 27510628
TI - Differentiation of mass-forming focal pancreatitis from pancreatic ductal
adenocarcinoma: value of characterizing dynamic enhancement patterns on contrast
enhanced MR images by adding signal intensity color mapping.
AB - OBJECTIVES: To evaluate the value of dynamic enhancement patterns on contrast
enhanced MR images by adding signal intensity colour mapping (SICM) to
differentiate mass-forming focal pancreatitis (MFFP) from pancreatic ductal
adenocarcinoma (PDAC). METHODS: Forty-one clinicopathologically proven MFFPs and
144 surgically confirmed PDACs were enrolled. Laboratory and MR imaging
parameters were used to differentiate MFFP from PDAC. In particular, enhancement
patterns on MR images adding SICM were evaluated. By using classification tree
analysis (CTA), we determined the predictors for the differentiation of MFFP from
PDAC. RESULTS: In the CTA, with all parameters except enhancement pattern on SICM
images, ductal obstruction grade and T1 hypointensity grade of the pancreatic
lesion were the first and second splitting predictor for differentiation of MFFP
from PDAC, in order. By adding an enhancement pattern on the SICM images to CTA,
the enhancement pattern was the only splitting predictor to differentiate MFFP
from PDAC. The CTA model including enhancement pattern on SICM images has
sensitivity of 78.0 %, specificity of 99.3 %, and accuracy of 94.6 % for
differentiating MFFP from PDAC. CONCLUSION: The characterization of enhancement
pattern for pancreatic lesions on contrast-enhanced MR images adding SICM would
be helpful to differentiate MFFP from PDAC. KEY POINTS: * SICM was useful to
characterize enhancement pattern. * Enhancement pattern on SICM was the only
splitting predictor on CTA. * This model may be useful for differentiating MFFP
from PDAC.
PMID- 27510629
TI - Arteries of the falciform ligament on C-arm CT hepatic arteriography: The hepatic
falciform artery and the Sappey's superior artery.
AB - BACKGROUND AND AIM: To investigate the prevalence, anatomy and distribution of
the hepatic falciform artery (HFA) and Sappey's superior artery (SSA) using C-arm
CT hepatic arteriography (C-arm CTHA). MATERIALS AND METHODS: From January 2011
to December 2012, 220 patients who underwent C-arm CTHA during initial
transarterial treatment for hepatocellular carcinoma were included in this
retrospective study. The HFAs and SSAs prevalence and origin were evaluated using
axial images of C-arm CTHA. A 5-point scale for HFAs and a 4-point scale for SSAs
were used to designate the radiologically conspicuous arteries. RESULTS: The
prevalences of the total HFAs and SSAs were 95 % (n=209) and 22 % (n=49), while
those of radiologically conspicuous HFAs and SSAs were 62 % (n=137) and 10 %
(n=22), respectively. Thirty HFAs (22 % of radiologically conspicuous HFAs and 14
% of the total study population) were distributed in the subcutaneous layer of
the anterior abdominal wall, while the majority of SSAs ran through the superior
part of the falciform ligament in the left-anterior direction and anastomosed
with left inferior phrenic artery. CONCLUSION: Our study using C-arm CTHA
revealed that the prevalence of the HFA is higher than the existing knowledge and
proved the existence of the SSA radiologically for the first time. KEY POINTS: *
Prevalence of hepatic falciform artery is 95 %, higher than previously known. *
22 % of conspicious hepatic falciform arteries distributed in subcutaneous tissue
around umbilicus. * The existence of Sappey's superior artery was proved with a
radiological method.
PMID- 27510631
TI - Michael Sharpe: Psychiatry was no "waste of a career".
PMID- 27510630
TI - 3D-black-blood 3T-MRI for the diagnosis of thoracic large vessel vasculitis: A
feasibility study.
AB - OBJECTIVES: To evaluate the feasibility of T1w-3D black-blood turbo spin echo
(TSE) sequence with variable flip angles for the diagnosis of thoracic large
vessel vasculitis (LVV). METHODS: Thirty-five patients with LVV, diagnosed
according to the current standard of reference, and 35 controls were imaged at
3.0T using 1.2 * 1.3 * 2.0 mm3 fat-suppressed, T1w-3D, modified Volumetric
Isotropic TSE Acquisition (mVISTA) pre- and post-contrast. Applying a navigator
and peripheral pulse unit triggering (PPU), the total scan time was 10-12 min.
Thoracic aorta and subclavian and pulmonary arteries were evaluated for image
quality (IQ), flow artefact intensity, diagnostic confidence, concentric wall
thickening and contrast enhancement (CWT, CCE) using a 4-point scale. RESULTS: IQ
was good in all examinations (3.25 +/- 0.72) and good to excellent in 342 of 408
evaluated segments (83.8 %), while 84.1 % showed no or minor flow artefacts. The
interobserver reproducibility for the identification of CCE and CWT was 0.969 and
0.971 (p < 0.001) with an average diagnostic confidence of 3.47 +/- 0.64. CCE and
CWT were strongly correlated (Cohen's k = 0.87; P < 0.001) and significantly more
frequent in the LVV-group (52.8 % vs. 1.0 %; 59.8 % vs. 2.4 %; P < 0.001).
CONCLUSIONS: Navigated fat-suppressed T1w-3D black-blood MRI with PPU-triggering
allows diagnosis of thoracic LVV. KEY POINTS: * Cross-sectional imaging is
frequently applied in the diagnosis of LVV. * Navigated, PPU-triggered, T1w-3D
mVISTA pre- and post contrast takes 10-12 min. * In this prospective, single
centre study, T1w-3D mVISTA accurately depicted large thoracic vessels. * T1w-3D
mVISTA visualized CWT/CCW as correlates of mural inflammation in LVV. * T1w-3D
mVISTA might be an alternative diagnostic tool without ionizing radiation.
PMID- 27510632
TI - Pretreatment neutrophil-to-lymphocyte ratio and its dynamic changes are
associated with the overall survival in advanced cancer patients undergoing
palliative care.
AB - The objective of this study was to investigate the prognostic value of
pretreatment NLR and its dynamic changes responsive to palliative care in
advanced cancer patients. The study was retrospectively assessed in 378
consecutive advanced cancer patients receiving palliative care, and in an
extended follow-up study of 106 of those patients. The cutoff value of
pretreatment NLR was determined to be 3.0. In the 378 advanced cancer patients,
89 had pretreatment NLR <= 3, and 289 had an NLR > 3. Univariate and multivariate
analyses showed that tumor stage, palliative care, albumin level, and
pretreatment NLR (HR: 1.514, 95% CI: 1.125~2.038, P = 0.006) were independent
prognostic indicators of OS. Moreover, in the follow-up cohort of 106 readmitted
patients, 43 patients achieved a decreased NLR after palliative care, while the
remaining 63 patients showed an increased NLR. Univariate and multivariate
analyses showed that an increase in NLR was significantly associated with a poor
survival (HR: 2.506, 95% CI: 1.474~4.261, P = 0.001). In conclusion, pretreatment
NLR and changes in NLR independently predicted OS in advanced cancer patients
undergoing palliative care. Incorporating NLR into clinical practice may better
inform the prognosis and therapy decisions of advanced cancer patients in
palliative settings.
PMID- 27510633
TI - Main competences and skills to perform Essential Public Health Operations,
offered by Schools of Public Health in four European countries: a short pilot
report.
AB - OBJECTIVES: To consider the stage of implementation of main competences and EPHO
skills in selected schools of public health in four European countries-France,
Poland, Portugal, and the UK. METHODS: By use of visual analogue scales (VAS)
ranging 1-5, the leads of three schools of public health (SPH) in each of the
four countries, France, Poland, Portugal and the UK, reported the strength of
intellectual and practical competences as well as skills to perform essential
public health operations (EPHOs), offered by their education and training
programmes. RESULTS: The self-reports indicated substantial coverage of the
multidimensional public health discipline. Each country representation had its
overall characteristic profile, and there was found noteworthy within-country as
well as between-country variation. CONCLUSIONS: The schools should meet the
challenge of establishing collaborative networks, which will be important for
public health strategy making and implementation, for shaping a coherent public
health profession, and thus ultimately for population health. This pilot report
should be followed up by more systematically penetrating and comprehensive
analyses to identify met and unmet needs in public health education and training.
PMID- 27510634
TI - Projected increase in amyotrophic lateral sclerosis from 2015 to 2040.
AB - Although amyotrophic lateral sclerosis (ALS) is relatively rare, the
socioeconomic significance of the disease is extensive. It is therefore vital to
project the epidemiologic trend of ALS. To date, there have been few published
studies attempting to estimate the number and distribution of ALS cases in the
upcoming years. Here we show that the number of ALS cases across the globe will
increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of
69%. This increase is predominantly due to ageing of the population, particularly
among developing nations. This projection is likely an underestimate due to
improving healthcare and economic conditions. The results should be used to
inform healthcare policy to more efficiently allocate healthcare resources.
PMID- 27510635
TI - Population PK Modeling and Target Attainment Simulations to Support Dosing of
Ceftaroline Fosamil in Pediatric Patients With Acute Bacterial Skin and Skin
Structure Infections and Community-Acquired Bacterial Pneumonia.
AB - Ceftaroline, the active form of the prodrug ceftaroline fosamil, is approved for
use in adults with community-acquired bacterial pneumonia (CABP) or acute
bacterial skin and skin structure infections (ABSSSI) in the United States and
for similar indications in Europe. Pharmacokinetic (PK) data from 5 pediatric
(birth to <18 years) studies of ceftaroline fosamil were combined with PK data
from adults to update a population PK model for ceftaroline and ceftaroline
fosamil. This model, based on a data set including 305 children, was used to
conduct simulations to estimate ceftaroline exposures and percentage of time that
free drug concentrations were above the minimum inhibitory concentration
(%fT>MIC) for pediatric dose regimens. With dose regimens of 8 mg/kg every 8
hours (q8h) in children aged 2 months to <2 years and 12 mg/kg (up to a maximum
of 400 mg) q8h in children aged 2 years to <18 years or 600 mg q12h in children
aged 12 to <18 years, >90% of children were predicted to achieve a target of 36%
fT>MIC at an MIC of 2 mg/L, and >97% were predicted to achieve 44% fT>MIC at an
MIC of 1 mg/L. Thus, high PK/pharmacodynamic target attainment would be
maintained in children for targets associated with 1-log kill of Staphylococcus
aureus and Streptococcus pneumoniae. The predicted ceftaroline exposures for
these dose regimens were similar to those in adults given 600 mg q12h ceftaroline
fosamil. This work contributed to the approval of dose regimens for children aged
2 months to <18 years by the FDA and EMA, which are presented.
PMID- 27510636
TI - Description of excited states in [Re(Imidazole)(CO)3 (Phen)](+) including solvent
and spin-orbit coupling effects: Density functional theory versus
multiconfigurational wavefunction approach.
AB - The low-lying electronic excited states of [Re(imidazole)(CO)3 (phen)](+) (phen =
1,10-phenanthroline) ranging between 420 nm and 330 nm have been calculated by
means of relativistic spin-orbit time-dependent density functional theory (TD
DFT) and wavefunction approaches (state-average-CASSCF/CASPT2). A direct
comparison between the theoretical absorption spectra obtained with different
methods including SOC and solvent corrections for water points to the
difficulties at describing on the same footing the bands generated by metal-to
ligand charge transfer (MLCT), intraligand (IL) transition, and ligand-to-Ligand-
charge transfer (LLCT). While TD-DFT and three-roots-state-average CASSCF (10,10)
reproduce rather well the lowest broad MLCT band observed in the experimental
spectrum between 420 nm and 330 nm, more flexible wavefunctions enlarged either
by the number of roots or by the number of active orbitals and electrons
destabilize the MLCT states by introducing IL and LLCT character in the lowest
part of the absorption spectrum. (c) 2016 Wiley Periodicals, Inc.
PMID- 27510637
TI - Polycystic ovary syndrome.
AB - Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age
worldwide. The condition is characterized by hyperandrogenism, ovulatory
dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen
production by the ovaries being a key feature of PCOS. Metabolic dysfunction
characterized by insulin resistance and compensatory hyperinsulinaemia is evident
in the vast majority of affected individuals. PCOS increases the risk for type 2
diabetes mellitus, gestational diabetes and other pregnancy-related
complications, venous thromboembolism, cerebrovascular and cardiovascular events
and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the
presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be
tailored to the complaints and needs of the patient and involves targeting
metabolic abnormalities through lifestyle changes, medication and potentially
surgery for the prevention and management of excess weight, androgen suppression
and/or blockade, endometrial protection, reproductive therapy and the detection
and treatment of psychological features. This Primer summarizes the current state
of knowledge regarding the epidemiology, mechanisms and pathophysiology,
diagnosis, screening and prevention, management and future investigational
directions of the disorder.
PMID- 27510638
TI - Mechanical response of all-MoS2 single-layer heterostructures: a ReaxFF
investigation.
AB - Molybdenum disulfide (MoS2) is a highly attractive 2D material due to its
interesting electronic properties. Recent experimental advances confirm the
possibility of further tuning the electronic properties of MoS2 through the
fabrication of single-layer heterostructures consisting of semiconducting (2H)
and metallic (1T) MoS2 phases. Nonetheless, despite significant technological and
scientific interest, there is currently limited information concerning the
mechanical properties of these heterostructure systems. This investigation aims
at extending our understanding of the mechanical properties of all-MoS2 single
layer structures at room temperature. This goal was achieved by performing
extensive classical molecular dynamics simulations using a recently developed
ReaxFF force field. We first studied the direction dependent mechanical
properties of defect-free 2H and 1T phases. Our modelling results for pristine 2H
MoS2 were found to be in good agreement with the experimental tests and first
principles theoretical predictions. We also discuss the mechanical response of
2H/1T single layer heterostructures. Our reactive molecular dynamics results
suggest all-MoS2 heterostructures as suitable candidates for providing a strong
and flexible material with tuneable electronic properties.
PMID- 27510639
TI - CISD1 inhibits ferroptosis by protection against mitochondrial lipid
peroxidation.
AB - Ferroptosis is a form of non-apoptotic cell death originally identified in cancer
cells. However, the key regulator of ferroptosis in mitochondria remains unknown.
Here, we show that CDGSH iron sulfur domain 1 (CISD1, also termed mitoNEET), an
iron-containing outer mitochondrial membrane protein, negatively regulates
ferroptotic cancer cell death. The classical ferroptosis inducer erastin promotes
CISD1 expression in an iron-dependent manner in human hepatocellular carcinoma
cells (e.g., HepG2 and Hep3B). Genetic inhibition of CISD1 increased iron
mediated intramitochondrial lipid peroxidation, which contributes to erastin
induced ferroptosis. In contrast, stabilization of the iron sulfur cluster of
CISD1 by pioglitazone inhibits mitochondrial iron uptake, lipid peroxidation, and
subsequent ferroptosis. These findings indicate a novel role of CISD1 in
protecting against mitochondrial injury in ferroptosis.
PMID- 27510640
TI - The GPI anchor pathway: a promising antifungal target?
PMID- 27510641
TI - Clustered marginalization of minorities during social transitions induced by co
evolution of behaviour and network structure.
AB - Large-scale transitions in societies are associated with both individual
behavioural change and restructuring of the social network. These two factors
have often been considered independently, yet recent advances in social network
research challenge this view. Here we show that common features of societal
marginalization and clustering emerge naturally during transitions in a co
evolutionary adaptive network model. This is achieved by explicitly considering
the interplay between individual interaction and a dynamic network structure in
behavioural selection. We exemplify this mechanism by simulating how smoking
behaviour and the network structure get reconfigured by changing social norms.
Our results are consistent with empirical findings: The prevalence of smoking was
reduced, remaining smokers were preferentially connected among each other and
formed increasingly marginalized clusters. We propose that self-amplifying
feedbacks between individual behaviour and dynamic restructuring of the network
are main drivers of the transition. This generative mechanism for co-evolution of
individual behaviour and social network structure may apply to a wide range of
examples beyond smoking.
PMID- 27510642
TI - Corrigendum.
PMID- 27510643
TI - RETRACTED: Investigation of the GeneXpert(r) CT/NG assay for use with male
pharyngeal and rectal swabs.
PMID- 27510644
TI - Stroke in a young patient with neurosyphilis and HIV.
AB - Syphilis has long been known as the great imitator. Its heterogeneity can
manifest in the form of meningitis, space occupying gummas, vasculitis, strokes,
cranial neuropathies, myelopathy, dementia, and seizures. The incidence has been
rising with each year, mainly in men who have sex with men accounting for 83% of
cases. With the coexistence of immunocompromised states, especially HIV (human
immunodeficiency virus), the usually chronic and insidious course of tertiary
neurosyphilis can be accelerated. Stroke can occur as a result of neurosyphilis
in its meningovascular form, and the likelihood of this increases with HIV co
infection, especially in high-risk groups such as intravenous drug users and men
who have sex with men. Here, we discuss a case of a young man who presented with
an ischemic stroke found to have neurosyphilis and HIV and consider the
management of these co-morbid conditions.
PMID- 27510645
TI - Low levels of neurocognitive impairment detected in screening HIV-infected men
who have sex with men: The MSM Neurocog Study.
AB - This study aimed to determine the prevalence of HIV neurocognitive impairment in
HIV-infected men who have sex with men aged 18-50 years, using a simple battery
of screening tests in routine clinical appointments. Those with suspected
abnormalities were referred on for further assessment. The cohort was also
followed up over time to look at evolving changes. HIV-infected participants were
recruited at three clinical sites in London during from routine clinical visits.
They could be clinician or self-referred and did not need to be symptomatic. They
completed questionnaires on anxiety, depression, and memory. They were then
screened using the Brief Neurocognitive Screen (BNCS) and International HIV
Dementia Scale (IHDS). Two hundred and five HIV-infected subjects were recruited.
Of these, 59 patients were excluded as having a mood disorder and two patients
were excluded due to insufficient data, leaving 144 patients for analysis. One
hundred and twenty-four (86.1%) had a normal composite z score (within 1 SD of
mean) calculated for their scores on the three component tests of the BNCS.
Twenty (13.9%) had an abnormal z score, of which seven (35%) were symptomatic and
13 (65%) asymptomatic. Current employment and previous educational level were
significantly associated with BNCS scores. Of those referred onwards for
diagnostic testing, only one participant was found to have impairment likely
related to HIV infection. We were able to easily screen for mood disorders and
cognitive impairment in routine clinical practice. We identified a high level of
depression and anxiety in our cohort. Using simple screening tests in clinic and
an onward referral process for further testing, we were not able to identify
neurocognitive impairment in this cohort at levels consistent with published
data.
PMID- 27510646
TI - Perforating domed plasmonic films for broadband and omnidirectional
antireflection.
AB - Domed Ag nano-hole/disk array films exhibit a reflectivity of less than 0.7% over
a wide spectral range (400-1000 nm) and even lower values down to 0.05% with an
oblique incidence angle; this unique optical response is attributed to three key
factors: diffractive scattering loss on nanostructures, localized plasmonic
absorption and curved surface (domed units).
PMID- 27510647
TI - Specific patterns of laryngeal electromyography during wakefulness are associated
to sleep disordered breathing and nocturnal stridor in multiple system atrophy.
AB - BACKGROUND: Nocturnal stridor and respiratory abnormalities are important
features of multiple system atrophy (MSA) with relevance to patient survival, and
they are detected and evaluated mainly through video-polysomnography (video-PSG).
Diurnal laryngoscopy seems to yield abnormal findings only in the presence of
significant vocal cord (VC) dysfunction. AIM: To assess whether specific
electrophysiological patterns of diurnal EMG of VC muscles may indicate nocturnal
stridor or respiratory dysfunctions in MSA patients. MATERIALS AND METHODS:
Seventeen patients with probable MSA were examined. A full-night video-PSG to
collect standard breathing parameters (apnea/hypopnea index, mean HbSAO2, oxygen
desaturation index, total sleep time with HbSaO2 below 90%) was performed in all
the patients. Laryngoscopy and EMG investigation of adductor (thyroarytenoid-TA)
and abductor (posterior cricoarytenoid-PCA) muscles of the VCs were also
performed. RESULTS: Both the laryngeal EMG abnormalities (based on MUAP analysis
and kinesiologic EMG investigation of VC muscles) and the laryngoscopic
alterations correlated with video-PSG respiratory abnormalities. Specific
patterns of EMG findings were consistently found in MSA subjects with nocturnal
stridor detected at PSG. In particular, the following EMG findings were related
to the severity of breathing abnormalities and the presence of stridor on video
PSG: neurogenic pattern on MUAP analysis of the PCA, paradoxical activation of
the TA during inspiration and tonic EMG activity of the TA during quiet
breathing. CONCLUSIONS: Electromyographic/kinesiologic investigation of VC
muscles during wakefulness provides additional information on the pathophysiology
of the respiratory abnormalities in MSA patients that could be useful for guiding
the choice of the best appropriate treatment and care.
PMID- 27510648
TI - Timing of Breeding Determines Growth and Development in a Long-Distance Migratory
Bird.
AB - The timing of breeding can have significant consequences for adult and offspring
fitness, yet our current hypotheses of seasonal timing focus on the parent
perspective. When offspring survival is affected by timing of breeding, we expect
to see offspring mechanisms to detect and respond to cues of seasonal timing.
Avian embryos respond to photoperiod and seasonal cues during development and in
this study we evaluate the influence of photoperiod and season on posthatching
growth and development in Franklin's gull (Leucophaeus pipixcan). Early- and late
season chicks exposed to short and long photoperiods during development were
reared under common garden conditions. Photoperiod had no effect on posthatching
growth and development, but seasonal effects present in the egg (maternal egg
effects or genetic) did influence posthatching growth and development. Late
season chicks grew body mass and primary flight feathers at faster rates than
early-season chicks, which we hypothesize facilitates independence and readiness
for migration. Growth rates are complex phenotypes and we propose a general
growth model that incorporates delays in negative feedback systems regulating
growth. We show that the timing of breeding programs intrinsic growth rates in
offspring, which suggests that many of the metrics used to describe seasonal
patterns of reproductive success may be biased.
PMID- 27510649
TI - Erratum to: Donor age and long-term culture do not negatively influence the stem
potential of limbal fibroblast-like stem cells.
PMID- 27510650
TI - Letter to the editor: Progressive neurology in a young woman with a known
Currarino's triad.
PMID- 27510651
TI - Identifying enriched drug fragments as possible candidates for metabolic
engineering.
AB - BACKGROUND: Fragment-based approaches have now become an important component of
the drug discovery process. At the same time, pharmaceutical chemists are more
often turning to the natural world and its extremely large and diverse collection
of natural compounds to discover new leads that can potentially be turned into
drugs. In this study we introduce and discuss a computational pipeline to
automatically extract statistically overrepresented chemical fragments in
therapeutic classes, and search for similar fragments in a large database of
natural products. By systematically identifying enriched fragments in therapeutic
groups, we are able to extract and focus on few fragments that are likely to be
active or structurally important. RESULTS: We show that several therapeutic
classes (including antibacterial, antineoplastic, and drugs active on the
cardiovascular system, among others) have enriched fragments that are also found
in many natural compounds. Further, our method is able to detect fragments shared
by a drug and a natural product even when the global similarity between the two
molecules is generally low. CONCLUSIONS: A further development of this
computational pipeline is to help predict putative therapeutic activities of
natural compounds, and to help identify novel leads for drug discovery.
PMID- 27510652
TI - Interleukin-1beta effect on the endogenous ADP-ribosylation and phosphorylation
of eukaryotic elongation factor 2.
AB - Eukaryotic elongation factor 2 (eEF2) plays an important role in eukaryotic
polypeptide chain elongation. Adenosine diphosphate (ADP)-ribosylation is a post
translational modification reaction that catalyzes the transfer of ADP-ribose
group to eEF2 and this causes the inhibition of protein synthesis. Indeed, in the
absence of diptheria toxin, endogenous ADP-ribosylation can occur. eEF2 is
phosphorylated by eEF2 kinase which prevents binding to ribosomes thus inhibiting
its activity. Increase in endogenous ADP-ribosylation level approximately 70-75 %
was observed in IL-1beta treated HUVECs. Moreover, a 70 % rise of phosphorylation
of eEF2 was measured. Alteration of endogenous ADP-ribosylation of eEF2 activity
was related with cellular mono-ADP-ribosyltransferases (ADPrT). Increment of
endogenous ADP-ribosylation on eEF2 did not seem to occur as a direct effect of
IL-1beta; it arises from the activation of ADPrT. This 2.5 fold increase was
abolished by ADPrT inhibitors. Due to these post-translational modifications,
global protein synthesis is inhibited. After dephosphorylation of phospho-eEF2,
around 20 % increase in protein synthesis was observed. In conclusion, systemic
IL-1beta has an important role in the regulation of global protein synthesis.
PMID- 27510653
TI - Effects of free amino acids on cytokine secretion and proliferative activity of
feline T cells in an in vitro study using the cell line MYA-1.
AB - In vitro studies might be an interesting screening method for targeted in vivo
studies in the field of immunonutrition and help to reduce and refine animal
studies. As the role of amino acids for immune function of cats has not been
evaluated in detail so far, the present study aimed at investigating the effects
of eight different amino acids (arginine, leucine, isoleucine, valine, glutamine,
lysine, threonine and tryptophan) in six concentrations each (0, 0.25, 0.5, 1, 2
and 8x the cat blood level) on cytokine secretion and proliferative activity of
feline T cells (MYA-1) in vitro. The results demonstrated that high doses of
arginine increased IL-4, IL-10 and TNF-alpha secretion of T cells, while
increasing concentrations of lysine increased IL-10 secretion and proliferative
activity of the T cells. High doses of leucine enhanced GM-CSF and IL-10
secretion, while concentrations of threonine in the cell culture media greater
than blood concentration also increased GM-CSF and additionally TNF-alpha
secretion of the cells. The effects of glutamine and isoleucine on T cell
function were only small. In conclusion, the present in vitro study could
evaluate the immunomodulating potential of specific amino acids for feline T cell
function. High doses of arginine, lysine, leucine and threonine had a significant
impact on cytokine secretion and proliferative activity of the T cells. Targeted
in vivo studies should investigate the clinical relevance of dietary
supplementation of those amino acids in healthy and diseased cats as a next step.
PMID- 27510654
TI - Weight Change in Midlife and Risk of Mortality From Dementia up to 35 Years
Later.
AB - Background: The relationship between body mass index (BMI) and dementia is
complex and controversial. This study investigates the association of weight
change during midlife and later dementia-related mortality. Methods: Two BMI
measurements (average of 9.0 years apart) were available for 43,721 participants
in the Norwegian Counties Study (NCS), with mean age 42 years at first BMI
measurement and 51 at the final measurement. NCS was linked with the Cause of
Death Registry until year 2015 (mean follow-up time 25.9 years). Cox regression
with a conditional growth model was used. Results: Our study comprised 1,205
dementia-related deaths. Weight loss was associated with increased dementia
related mortality, irrespectively of baseline BMI and confounders; those with 10%
or more loss had hazard ratio (HR) = 1.52 (95% confidence interval [CI]: 1.09,
2.12) compared to those being stable (0%-2.5% BMI gain), and those with 5%-10%
loss had HR = 1.38 (95% CI: 1.08, 1.76). Gaining weigh was associated with
reduced dementia-related mortality. Associations with BMI change did not vary by
baseline BMI. Conclusions: Weight loss during midlife was associated with
increased dementia-related mortality risk more than 3 decades later, while weight
gain was associated with reduced risk. These associations held both for low and
high baseline BMI. Weight loss was an independent risk factor for dementia
related mortality and more strongly related with dementia-related mortality than
stable BMI (stable high or low). Overweight and obesity were associated with an
increased risk for nondementia-related mortality, which was far more common than
dementia-related mortality.
PMID- 27510656
TI - From Editor's desk.
PMID- 27510657
TI - Combination of laboratory diagnostic tests for cutaneous tuberculosis.
PMID- 27510655
TI - Systemic availability and metabolism of colonic-derived short-chain fatty acids
in healthy subjects: a stable isotope study.
AB - KEY POINTS: The short-chain fatty acids (SCFAs) are bacterial metabolites
produced during the colonic fermentation of undigested carbohydrates, such as
dietary fibre and prebiotics, and can mediate the interaction between the diet,
the microbiota and the host. We quantified the fraction of colonic administered
SCFAs that could be recovered in the systemic circulation, the fraction that was
excreted via the breath and urine, and the fraction that was used as a precursor
for glucose, cholesterol and fatty acids. This information is essential for
understanding the molecular mechanisms by which SCFAs beneficially affect
physiological functions such as glucose and lipid metabolism and immune function.
ABSTRACT: The short-chain fatty acids (SCFAs), acetate, propionate and butyrate,
are bacterial metabolites that mediate the interaction between the diet, the
microbiota and the host. In the present study, the systemic availability of SCFAs
and their incorporation into biologically relevant molecules was quantified.
Known amounts of 13 C-labelled acetate, propionate and butyrate were introduced
in the colon of 12 healthy subjects using colon delivery capsules and plasma
levels of 13 C-SCFAs 13 C-glucose, 13 C-cholesterol and 13 C-fatty acids were
measured. The butyrate-producing capacity of the intestinal microbiota was also
quantified. Systemic availability of colonic-administered acetate, propionate and
butyrate was 36%, 9% and 2%, respectively. Conversion of acetate into butyrate
(24%) was the most prevalent interconversion by the colonic microbiota and was
not related to the butyrate-producing capacity in the faecal samples. Less than
1% of administered acetate was incorporated into cholesterol and <15% in fatty
acids. On average, 6% of colonic propionate was incorporated into glucose. The
SCFAs were mainly excreted via the lungs after oxidation to 13 CO2 , whereas less
than 0.05% of the SCFAs were excreted into urine. These results will allow future
evaluation and quantification of SCFA production from 13 C-labelled fibres in the
human colon by measurement of 13 C-labelled SCFA concentrations in blood.
PMID- 27510658
TI - Salivary gland anlage tumor in a neonate.
PMID- 27510659
TI - Evaluation of laboratory diagnosis for cutaneous tuberculosis.
AB - BACKGROUND AND AIM: Cutaneous tuberculosis (CTB) is still difficult to diagnose
due to its varied clinical presentation and limitations of diagnostic methods.
The aim of this study was to evaluate the results of diagnostic laboratory tests
available for CTB. MATERIALS AND METHODS: Twenty-six skin biopsy specimens
belonging to clinically suspected cases of CTB were studied retrospectively. The
specimens were divided into two portions, one part processed for
histopathological evaluation and the other was used for microscopy and
inoculation for the isolation of mycobacteria. Polymerase chain reaction (PCR)
technique was applied to 14 of 26 specimens to detect Mycobacterium tuberculosis
complex (MTBC) DNA. RESULTS: Of the 26 biopsy specimens, 11 were confirmed as CTB
by identification of MTBC in culture and/or histopathologic affirmation. Of
these, four were lupus vulgaris, four were TB verrucosa cutis, one was
scrofuloderma, one was primary inoculation TB, and one was periorifical CTB.
Culture for mycobacteria was positive for five (45.45%) specimens, while
histopathologic affirmation was obtained in ten (90.90%) specimens. Acid-fast
Bacilli were not demonstrated in any of the specimens on microscopic examination.
The PCR was found to be applied to six of the 11 specimens diagnosed as CTB and
was positive in two specimens (33.3%), which were positive for growth in culture
and histopathological correlation. CONCLUSION: The recovery rate of MTBC from
biopsy specimens was found to be satisfactory for CTB with histopathological
correlation, but the combination of culture with a rapid method, PCR, may improve
the diagnostic rate.
PMID- 27510660
TI - Pathology of thyroid in acquired immunodeficiency syndrome.
AB - BACKGROUND: The course of human immunodeficiency virus infection and the acquired
immunodeficiency syndrome can be complicated by a variety of endocrine
abnormalities, including abnormalities of thyroid gland. MATERIALS AND METHODS:
This study was designed to understand the spectrum of pathology of thyroid in
Indian patients with AIDS. The present study describes the findings of
retrospective autopsy findings of 158 patients with AIDS which revealed
infectious diseases from a time period before the use of highly active
antiretroviral regimen. RESULTS: A wide range of bacterial, fungal, and viral
infections were observed. Tuberculosis was recorded in 14 (09%) patients,
Cryptococcus neoformans in 11 (7%) patients and cytomegalovirus in 3 (2%)
patients. Hashimoto's thyroiditis and lymphocytic thyroiditis were seen in 02
(01%) patients each. One patient had dual infection comprising of tuberculosis
and cytomegalovirus infection. The other microscopic findings observed were
goiter (2 patients), interstitial fibrosis in thyroid (7 patients), and
calcification in thyroid (8 patients). CONCLUSIONS: Abnormalities of thyroid are
uncommon findings in patients with HIV infection however several case reports of
thyroid involvement by infectious agents and neoplasm are described in these
patients; hence patients with HIV infection should be closely followed up for
development of goiter or abnormalities of thyroid functions.
PMID- 27510661
TI - Apoptosis in oral epithelial dysplastic lesions and oral squamous cell carcinoma:
A prognostic marker.
AB - BACKGROUND: Apoptotic index (AI) using light microscopy as an indirect measure to
assess the significance of apoptosis as a proliferative marker in dysplastic
lesions and malignant epithelial lesions of the oral cavity. AIMS: (1) To
quantify the apoptotic bodies/cells in oral epithelial dysplastic (OED) lesions
and oral squamous cell carcinoma (OSCC). (2) To measure AI in OED and OSCC. (3)
To compare AI in OED and OSCC. SETTINGS AND DESIGN: The proposed laboratory-based
retrospective study involved the use of hematoxylin and eosin (H and E)-stained
slides of previously diagnosed OED lesions and OSCC from institutional archives.
MATERIALS AND METHODS: This study constituted 50 cases, each of H and E-stained
slides of previously diagnosed cases of OED and OSCC. AI was calculated as the
number of apoptotic bodies/cells expressed as a percentage of the total number of
nonapoptotic tumor/dysplastic cells counted in each case. STATISTICAL ANALYSIS
USED: Nonparametric tests such as Kruskal-Wallis test and Mann-Whitney test were
used. RESULTS: There was a statistically significant increase in AI from OED to
OSCC (P = 0.000). CONCLUSIONS: Further studies need to be undertaken to detect
and understand the apoptotic mechanisms in the progression from OED to OSCC.
PMID- 27510662
TI - Do phosphatase of regenerating liver-3, matrix metalloproteinases-2, matrix
metalloproteinases-9, and epidermal growth factor receptor-1 predict response to
therapy and survival in glioblastoma multiforme?
AB - CONTEXT: Poor survival of the glioblastoma multiforme (GBM) has been attributed
in part to the invasive nature of the lesion making complete surgical removal
near impossible. Phosphatase of regenerating liver-3 (PRL-3), matrix
metalloproteinases-2 and -9 (MMP-2 and MMP-9), and epidermal growth factor
receptor (EGFR-1) play a role in invasive nature of tumor cells. AIMS: This study
was conducted to evaluate PRL-3, MMP-2, MMP-9, and EGFR-1 (markers) expression in
cases to GBM and to correlate their expression with therapy response and
survival. SETTINGS AND DESIGN: GBM cases (n = 62) underwent surgery followed by
radiation (n = 34) and chemoradiation (n = 28). Using WHO Response Evaluation
Criteria in Solid Tumors criteria response to therapy was assessed at 3 months
and cases followed up for survival. SUBJECTS AND METHODS: Expression of markers
was assessed by immunohistochemistry as a percentage of positive tumor cells in
hot spots. STATISTICAL ANALYSIS USED: Kaplan-Meier, ANOVA, Chi-square test,
univariate, and multivariate Cox-regression analysis was done. RESULTS: Response
to therapy was evident in 54.8% cases of responders with the mean survival of
494.03 +/- 201.13 days and 45.2% cases of non responders (278.32 +/- 121.66 days)
with P = 0.001. Mean survival for the patient's opted chemoradiation was 457.43
+/- 222.48 days which was approximately 3 months greater than those who opted
radiation alone (P = 0.029). We found PRL-3 overexpression was an independent,
significant, poor prognostic factor for survival by multivariate analysis (P =
0.044). Cases negative for MMP's and EGFR showed increased survival, but the
difference was insignificant. CONCLUSION: PRL-3 expression appears to be related
to an adverse disease outcome.
PMID- 27510663
TI - A tissue microarray study of toll-like receptor 4, decoy receptor 3, and external
signal regulated kinase 1/2 expressions in astrocytoma.
AB - INTRODUCTION: Decoy receptor 3 (DcR3) functions as a death decoy inhibiting
apoptosis mediated by the tumor necrosis factor receptor family. It is highly
expressed in many tumors and its expression can be regulated by the MAPK/ERK
signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4
(TLR4) is expressed on immune cells. Increased TLR4 expression has been
associated with various types of cancers. MATERIAL AND METHODS: The study was
conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas
and evaluate if they are validating markers for discriminating glioblastoma from
anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2,
and TLR4 was determined by immunohistochemical staining of tissue microarray from
48 paraffin-embedded tissues. A binary logistic regression method was used to
generate functions that discriminate between anaplastic astrocytomas and
glioblastomas. RESULTS: The expression of TLR4 and DcR3 was significantly higher
in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate
anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%),
specificity (90%), and accuracy (92.3%). CONCLUSION: Our results suggest that
DcR3 may be a useful marker for discriminating anaplastic astrocytomas from
glioblastomas.
PMID- 27510664
TI - The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha
expressions in uterine smooth muscle tumors.
AB - OBJECTIVES: This retrospective study was designed to evaluate the importance of
tissue expressions of caveolin-1 (Cav-1) and AT-rich interactive domain 1 alpha
(ARID-1A) which are known as signal regulator and tumor suppressor in
differential diagnosis of uterine smooth muscle tumors (SMTs). MATERIALS AND
METHODS: Thirty patients recently diagnosed as uterine SMTs at the Tepecik
Training and Research Hospital were identified using pathology databases.
Immunohistochemical stains for Cav-1 and ARID-1A were performed. RESULTS: In this
series, there were 10 leiomyosarcomas (LMSs), 10 uterine smooth muscle tumors of
uncertain malignant potentials (STUMPs), and 10 leiomyomas (LMs). Cav-1
expression located cytoplasmic or perivascular area. Cytoplasmic Cav-1 expression
was determined in 5 LMSs and 2 STUMPs while perivascular Cav-1 expression was
determined in 9 LMSs and 2 STUMPs. Statistically, it was determined that if the
tumor becomes malignant and more invasive, it gains the perivascular Cav-1
expression (P = 0.029). On the other hand, the mean nuclear staining rate for
ARID-1A in LMSs (63 +/- 23.4%) was higher than both STUMPs (60 +/- 18.5%) and LMs
(34.5 +/- 16.5%). Statistically, it was determined that the expression of ARID-1A
was significantly downregulated in LMs when compared with STUMPs and LMSs (P =
0.004). CONCLUSIONS: Our findings were demonstrated that perivascular Cav-1
expression was seen to be a marker for malignancy of uterine SMTs. Similarly, we
found to link of ARID-1A expression and the aggressiveness of SMTs. Therefore, it
may be suggested that Cav-1 and ARID-1A may act as predictive biomarkers in
uterine SMTs.
PMID- 27510665
TI - Comparative evaluation of immunoperoxidase versus immunofluorescent techniques in
interpretation of kidney biopsies.
AB - BACKGROUND: Immunofluorescence (IF) on frozen sections has been considered to be
the gold standard for evaluation of kidney biopsy specimens. Immunohistochemistry
(IHC) method can also be used for this purpose with advantages of being
applicable on paraffin embedded tissue, providing permanent sections, and not
requiring a specialized microscope for interpretation. Our aim was to evaluate
IHC as an alternative to IF in the diagnostic assessment of kidney biopsy
specimens. METHODS: One hundred kidney biopsy specimens were subjected to both IF
and IHC staining for immunoglobulins (Ig), IgG, IgA, IgM and complement
components c3 and c1q. IF staining was done on frozen sections. IHC staining was
performed on paraffin-embedded tissue following proteolytic antigen retrieval.
The sections were evaluated, and the results of IHC were compared with IF.
RESULTS: Concordant observations were 98%, 87%, 89%, 83%, and 89% for IgA, IgM,
IgG, C3 and C1q, respectively. The sensitivity of IHC method for Igs was found to
be high (92%, 86.5%, and 95.1%, respectively for IgA, IgM, and IgG). 91% cases
showed concordance of the intensity of the deposits while 100% cases showed a
concordance of the pattern. Statistically, there was no significant difference in
outcomes between IF and IHC for IgA, IgM, and IgG. However, statistically
significant difference was found in the results for complement proteins.
CONCLUSION: In this study, it is documented that IHC is, with few exceptions,
equal to IF for the detection of Igs. Standardized immunoperoxidase method on the
paraffin embedded, formalin fixed needle kidney biopsies could successfully
replace the IF method in the diagnosis of glomerulonephritis.
PMID- 27510666
TI - Expression of CD71 by flow cytometry in acute leukemias: More often seen in acute
myeloid leukemia.
AB - BACKGROUND: CD71 is a marker that has been usually used for identifying dysplasia
in the erythroid series. We have tried to evaluate the expression of CD71 in
various types of acute leukemias. MATERIALS AND METHODS: We studied 48 patients
of acute leukemia, of which 25 were acute myeloid leukemia (AML), 13 were
precursor B-acute lymphoblastic leukemia (B-ALL), 8 were T-ALL, and 2 were mixed
phenotype acute leukemia (T/myeloid) as per the WHO classification. RESULTS: We
found that the expression of CD71 was most prevalent in AMLs (84%), followed by T
ALL (50%) and least in B-ALL (30%). CONCLUSION: This finding clearly shows the
higher expression of CD71 in AMLs compared to other common type of leukemias,
such as B- and T-ALL. We suggest that the high expression of CD71 in AMLs could
be used as a diagnostic marker and may also be used for minimal residual disease
analysis after further studies in posttreatment scenario. This study is the first
of its kind in the South Asian population.
PMID- 27510667
TI - Comparative analysis of phenotypic and genotypic detection of methicillin
resistance among Staphylococcus aureus.
AB - AIMS: Staphylococcus aureus is a common pathogen causing a wide range of
infections ranging from mild skin and soft tissue infections to severe, life
threatening infections. Accuracy in the detection of methicillin resistance is
important to avoid treatment failures. The aim of this study was to compare the
results of phenotypic and genotypic test methods to detect methicillin resistance
and also to determine the antimicrobial susceptibilities. MATERIALS AND METHODS:
Two hundred and forty-two S. aureus strains isolated from skin and soft tissue
samples were analyzed for methicillin resistance using oxacillin and cefoxitin
disk diffusion (DD), oxacillin screen agar test, cefoxitin E-test, and mecA gene
polymerase chain reaction (PCR). RESULTS: 77 of 242 S. aureus isolates were mecA
positive. Oxacillin, cefoxitin DD, oxacillin screen agar test and cefoxitin E
test exhibited sensitivities as 98.7%, 98.7%, 100%, 100%, and specificities as
96.9%, 97.5%, 96.9%, 97.5%, respectively. CONCLUSION: Results of oxacillin screen
agar and cefoxitin DD test were in concordance with mecA gene PCR. Thus, it is
determined that especially cefoxitin test can be an alternative to PCR in
routine.
PMID- 27510669
TI - Distribution of plasmid-mediated quinolone resistance in Gram-negative bacteria
from a tertiary hospital in Nigeria.
AB - BACKGROUND: Until recently, mechanisms of resistance to quinolones in Gram
negative bacteria were believed to be only chromosome encoded. However, emergence
of plasmid-mediated quinolone resistance (PMQR) has been reported worldwide. AIM:
This study investigated distribution of PMQR in Gram-negative bacteria from a
tertiary hospital in eastern part of Nigeria. MATERIALS AND METHODS: Seventy-one
nonduplicate Gram-negative bacterial isolates of eight species were analyzed for
antimicrobial susceptibility, genotypic detection of various PMQRs, typed by
random amplified polymorphic DNA (RAPD) and analysis of plasmids present,
including replicon typing. RESULTS: The minimum inhibitory concentrations showed
MIC90values as high as 256 MUg/ml for fluoroquinolones. Carriage of PMQR was
found to be 35.2%. Twenty (28.2%) isolates carried various qnr genes, of which
seven (9.9%) qnrA1; four (5.6%) qnrB1; eight (11.3%) qnrS1 while one (1.4%)
encoded qnrD1. Eighteen (25.4%) isolates were positive for aac(6')-Ib-cr while
carriage of multiple genes exists in some strains. Similarly, 13 isolates (18.7%)
were found to carry PMQR efflux pump gene, qepA. Conjugation experiments revealed
that the plasmids once transferred coded for fluoroquinolone resistance. The
transconjugant strains carried a common plasmid estimated to be 65 kb. These
plasmids were untypable for replicon/incompatibility. Typing revealed high
diversity among all species tested with no identical RAPD pattern seen.
CONCLUSION: This study further confirms high level resistance to many
antimicrobials in different species of Gram-negative bacteria including
fluoroquinolones and spread of PMQR genes in Southern Nigeria.
PMID- 27510668
TI - Role of type-specific herpes simplex virus-1 and 2 serology as a diagnostic
modality in patients with clinically suspected genital herpes: A comparative
study in Indian population from a tertiary care hospital.
AB - INTRODUCTION: Type-specific serology (TSS) test for herpes simplex virus (HSV)
have been used as a research tool in seroepidemiological studies for some years.
However, TSS as a diagnostic modality for diagnosis of current episode of genital
herpes is not well documented. AIMS AND OBJECTIVES: To measure the seroprevalence
of type-specific HSV Type 1 (HSV-1) and Type 2 (HSV-2) IgG antibodies in cases
provisionally diagnosed as primary and recurrent genital herpes and to evaluate
the role of TSS as a diagnostic modality for diagnosis of genital herpes versus
polymerase chain reaction (PCR). MATERIALS AND METHODS: A cross-sectional study
was performed over a period of 10 months in which 44 adult patients with
clinically suspected genital herpes were recruited. An in-house glycoprotein G
gene base PCR was performed directly from the genital lesion specimen for
simultaneous detection and typing of HSV. TSS was performed to detect IgG
antibody against HSV-1 and 2 in all patients using commercially available kits,
and the results were compared. RESULTS: Seroprevalence of HSV-1 IgG was 43% among
primary and 65% among recurrent genital herpes cases (P = 0.22). Whereas that of
HSV-2 IgG was found to be 14% and 83% in respective patient group (P = 0.0001).
When compared to PCR results HSV-1 IgG detection in both primary and recurrent
genital herpes diagnosis had poor specificity, positive predictive value, and
sensitivity. Whereas, HSV-2 serology had a sensitivity of 13.33% and 73.33% in
primary and recurrent genital herpes and specificity of 83.33% and 85.71%,
respectively. CONCLUSION: HSV-2 IgG detection helps in strengthening the
diagnosis of recurrent HSV-2 disease, whereas the absence of HSV-2 IgG antibody
helps in excluding genital herpes as a likely cause of recurrent genital
ulceration. However, detection of HSV-1 IgG antibody may not be useful for
diagnosis in patients of genital ulcer disease.
PMID- 27510671
TI - Comparison of multiplex RT-PCR and real-time HybProbe assay for serotyping of
dengue virus using reference strains and clinical samples from India.
AB - BACKGROUND: Dengue virus serotyping is crucial from clinical management and
epidemiological point of view. AIMS: To compare efficacy of two molecular
detection and typing methods, namely, multiplex reverse transcription polymerase
chain reaction (RT-PCR) and real-time Hybprobe assay using a panel of known
dilution of four reference Dengue virus strains and a panel of sera collected
from clinically suspected dengue patients. SETTINGS: This study was conducted at
a tertiary-care teaching hospital in Delhi, India. MATERIALS AND METHODS: Dengue
serotype specific virus strains were used as prototypes for serotyping assays.
Viral load was quantified by quantitative real time reverse transcription
polymerase chain reaction (qRT-PCR). Acute phase serum samples were collected
from 79 patients with clinically suspected Dengue fever on their first day of
presentation during September-October 2012. Viral RNA from serum and cell culture
supernatant was extracted. Reverse transcription was carried out. Quantitative
detection of DENV RNA from reference strain culture supernatants and each of the
79 patient samples by real-time PCR was performed using light cycler Taqman
master mix kit. Serotyping was done by multiplex RT-PCR assay and Hybprobe assay.
RESULTS: The multiplex RT-PCR assay, though found to be 100% specific, couldn't
serotype either patient or reference strains with viral load less than 1000 RNA
copies/ml. The Hybprobe assay was found to have 100% specificity and had a lower
limit of serotype detection of merely 3.54 RNA copies/ml. CONCLUSIONS: HybProbe
assay has an important role especially in situations where serotyping is to be
performed in clinical samples with low viral load.
PMID- 27510670
TI - Emerging enteric fever due to switching biotype of Salmonella (paratyphi A) in
Eastern Odisha.
AB - BACKGROUND: Typhoid fever is classically caused by Salmonella enterica serotype
typhi.Recently the frequency of isolation of S. paratyphi A (SPA) has been
increased in comparison to S. typhi in Indian scenario. AIM: To observe the rate
of isolation and antimicrobial susceptibility pattern of SPA from suspected
enteric fever cases attending tertiary care centres of Eastern Orissa. SETTINGS
AND DESIGN: Retrospective study Materials and Methods: 1488 blood samples were
collected during different duration of fever and cultured in BACTEC blood culture
system and bottles showing signal for growth were subcultured and identified as
Salmonella spp. by standard procedure and mini API (Biomeriux) and antimicrobial
susceptibility by disc diffusion method. STATISTICAL ANALYSIS: Chi square test.
RESULTS: 167 Salmonella spp. were isolated including 83.8% Salmonella paratyphi A
and 16.6% S. typhi. Among them 102 were males and 65 were females with mean age
of 22.7 yrs. S. paratyphi A was the predominant spp. each year but during 2008 -
2011, there was a dramatic rise (significant P value- 0.034). Multidrug
resistance was noticed in 10.2% of the isolates. 98% of S. paratyphi A were
resistant to nalidixic acid and 41% to ciprofloxacin, but the MIC of
ciprofloxacin was raised between 1-2 MUgm/dl showing the relation between
nalidixic acid resistance and raised MIC of ciprofloxacin. CONCLUSION: Nalidixic
acid should be tested along with ciprofloxacin disc while testing for
susceptibility and MIC of ciprofloxacin is mandatory before advocating therapy to
prevent treatment failure.
PMID- 27510672
TI - A novel PTCH1 gene mutation in a pediatric patient associated multiple
keratocystic odontogenic tumors of the jaws and Gorlin-Goltz syndrome.
AB - Gorlin-Goltz syndrome (GGS) is an uncommon autosomal dominant inherited disorder
which comprises the triad of basal cell carcinomas (BCCs), odontogenic
keratocysts, and musculoskeletal malformations. Besides this triad, neurological,
ophthalmic, endocrine, and genital manifestations are known to be variable. It is
occasionally associated with aggressive BCC and internal malignancies. This
report documents a case of GGS with a novel mutation in the PTCH1 gene in an 11
year-old child. The clinical, radiographic, histopathologic and molecular
findings of this condition, and treatment are described, and a review of GGS was
carried out.
PMID- 27510673
TI - Severe liver dysfunction in an infant with cystic fibrosis masquerading as
metabolic liver disease.
AB - We present a rare presentation of cystic fibrosis with neonatal cholestasis.
Histological features of mucoviscidosis were present in liver involving the
biliary tract, intestinal mucosa, pancreas, and lung. Besides, there was a rare
association with autosomal dominant type of polycystic renal disease.
PMID- 27510674
TI - Solid pseudopapillary neoplasm of the ovary with metastases to the omentum and
regional lymph nodes.
AB - Extrapancreatic solid pseudopapillary neoplasms (SPNs) are rare tumors, which
bear morphological, immunohistochemical, and molecular features similar to those
of pancreatic counterparts. SPN occurs primarily in adolescent girls and young
women. It is considered to be a malignant neoplasm with low-grade biology.
Ovarian SPNs are uncommon, have benign morphology, usually limited to the ovary
and local surgical excision is curative. We report an unusual case of SPN of
right ovary with extraovarian spread and metastases to lymph nodes. To the best
of our knowledge, this is the second documented case of extragonadal spread of
ovarian SPN.
PMID- 27510675
TI - Primary thymic mediastinal seminoma with florid granulomatous reaction.
AB - Primary mediastinal seminomas are rare tumors. Morphologically, they can be
associated with secondary changes in the form of thymic remnants, cystic change,
epithelioid granulomas, abundant fibrosis, and syncytiotrophoblast like cells.
Ours was an interesting case where a 17-year-old adolescent male presented with
anterior mediastinal mass. Fine needle aspiration and trucut biopsy of the mass
favored tuberculosis; however, he did not respond to antituberculosis treatment
regime. He was subjected to video-assisted thoracoscopic surgery and the
histopathological examination along with supportive immunohistochemistry of the
mass revealed scattered seminoma cells which were being masked by extensive
granulomatous reaction. The aim of this article is to report a case of primary
mediastinal thymic seminoma in a young male associated with extensive
granulomatous reaction masking the neoplastic population of cells leading to
erroneous diagnosis on small biopsy.
PMID- 27510676
TI - Lipoleiomyoma of the left broad ligament with dermoid cyst in ipsilateral ovary
and synchronous multiple benign lesions of female genital tract: An unusual
association.
AB - Lipoleiomyoma of the uterus is a rare variant of leiomyoma, and lipoleiomyoma of
the broad ligament is still rarer, with only a handful of cases being reported.
The present case was a perimenopausal woman who presented with a huge lower
abdominal mass. Ultrasonography and computed tomography showed a heterogeneous
solid mass in the left adnexa. The histopathological findings confirmed the
nature of the lesions as a benign lipoleiomyoma with dermoid cyst of the left
ovary and its other associated benign lesions, were the interesting features seen
in this case which were not suspected clinically and radiologically.
PMID- 27510677
TI - Combined presence of multiple gastrointestinal stromal tumors along with duodenal
submucosal somatostatinoma in a patient with neurofibromatosis type 1.
AB - Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased
risk of developing benign and malignant tumors of the gastrointestinal tract
(GIT). However, the synchronous presence of multiple GIT stromal tumors and
duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1
patient, is very rare. She presented with hematemesis, malena, along with
multiple neurofibromas all over the body. Thorough radiological and peroperative
work-up revealed multiple ulcerated submucosal and serosal nodules in the
proximal small intestine. Histological work-up revealed diagnosis of a duodenal
submucosal somatostatinoma with multifocal serosal gastrointestinal stromal
tumors. This case is being reported to highlight the rare coincidence of multiple
GIT tumors in an NF-1 patient.
PMID- 27510678
TI - An unusual presentation of chondroid syringoma.
AB - Chondroid syringoma (CS) is a rare benign tumor of the sweat gland. It generally
presents as a painless, slowly growing, subcutaneous swelling, typically located
on the head and neck region. The majority of the cases develop in middle aged and
elderly males. We present a case of CS located over the right thumb of a 25-year
old male. The diagnosis was made initially by cytological evaluation and later
confirmed by histopathological examination. There was no recurrence on two year
follow up after the complete surgical excision of the tumor.
PMID- 27510679
TI - Isolated ileal ganglioneuromatosis in an 11-year-old boy: Case report and review
of literature.
AB - Ganglioneuromatous proliferation in the gastrointestinal tract is a rare
occurrence and is usually associated with specific syndrome complexes such as
multiple endocrine neoplasia Type 2B or von Recklinghausen's disease. We report
here a case of diffuse intestinal ganglioneuromatosis, presenting as intestinal
obstruction and chronic constipation in an 11-year-old boy. Sporadic cases of
intestinal ganglioneuromatosis in the absence of any systemic manifestations are
a very rare cause of enteric motility disorders in childhood, and we discuss the
pathological and clinical significance of this finding. Histopathological
identification of this uncommon cause of a common pediatric problem is important
since the condition is amenable to surgical treatment.
PMID- 27510680
TI - Cytomorphological findings and histological correlation of papillary
cystadenocarcinoma of the parotid: Not always a low-grade tumor.
AB - Papillary cystadenocarcinoma (PCAC) is a rare salivary gland tumor characterized
by a predominantly cystic growth that often exhibits intraluminal papillary
growth without specific histologic features of other cystic salivary gland
tumors. The preoperative cytological diagnosis can pose a diagnostic challenge as
it has to be differentiated from other cystic papillary tumors such as
mucoepidermoid carcinoma, papillary cystic variant of acinic cell carcinoma, and
low-grade cribriform CAC. It is considered to be a low-grade malignant salivary
gland tumor with an indolent biological behavior. We report a case of PCAC of the
parotid in a 55-year-old male diagnosed on fine needle aspiration cytology.
Although it showed mild atypia cytologically, on excision tumor showed vascular
and perineural invasion with regional node metastasis indicating a wider
morphologic spectrum than what is described. This prompted us to write a case
report describing the cytological and histological features of this rare tumor
and also discuss the diagnostic challenges.
PMID- 27510681
TI - Sertoli cell tumor arising in a cryptorchid testis presenting as a content of
inguinal hernial sac.
AB - Sertoli cell tumors (SCTs) are rare tumors accounting for <1% of all testicular
tumors. Here, we report a rare case of SCT in a 60-year-old man presenting as a
painless swelling in the right groin since childhood. Clinically, he presented
with right-sided inguinal hernia with absence of the right testis. He had normal
left testis and had no gynecomastia or infertility. The specimen of hernial sac
showed testis with a 1.6 cm * 1.5 cm nodular mass having gray tan-cut surface.
Histopathologically, the testis showed atrophy and the nodular portion showed
tumor cells arranged in tubular and microcystic pattern, with no solid pattern or
necrosis. The diagnosis of SCT was confirmed with immunohistochemical staining
for inhibin which showed fine granular cytoplasmic positivity. Cryptorchid testis
having SCT and presenting as a content of inguinal hernia is a rare occurrence.
PMID- 27510682
TI - Pseudoangiomatous variant of spindle cell lipoma: Report of a rare case.
AB - Pseudoangiomatous spindle cell lipoma is a rare variant of spindle cell lipoma.
It exhibits irregular and branching spaces with villiform connective tissue
projections, leading to formation of a characteristic angiomatoid pattern in
addition to benign spindle cells and mature adipocytes. Recent studies have shown
that these branching spaces are lined by endothelial cells and express markers.
Therefore, the term "angiomatous variant" instead of "pseudoangiomatous" has been
proposed for these lesions. We describe one of such lesions in the thumb of a
young female. To the best of our knowledge, this is the first reported case of
pseudoangiomatous variant of spindle cell lipoma from India.
PMID- 27510683
TI - Pleomorphic rhabdomyosarcoma of the left atrium mimicking myxoma.
AB - Primary rhabdomyosarcoma (RMS) of the heart is a rare malignant tumor which has
poor prognosis and survival despite surgery and adjuvant chemotherapy. The
preoperative diagnosis is often difficult in view of nonspecific
clinicoradiological findings. This report describes a case of a 60-year-old woman
who was clinically diagnosed as left atrial myxoma. A diagnosis of pleomorphic
RMS was made on histopathology after excision. Our case discusses the
clinicopathological features and treatment options of cardiac RMS emphasizing the
fact that histopathology and immunohistochemistry are essential to confirm the
diagnosis of such an aggressive malignant tumor.
PMID- 27510684
TI - A rare case of multifocal pseudomyogenic hemangioendothelioma, involving soft
tissues and bone, misdiagnosed as a rhabdomyosarcoma: Diagnostic and treatment
implications.
AB - Pseudomyogenic hemangioendothelioma (PHE) is an uncommon, but distinctive soft
tissue tumor, characterized by multifocality. A 17-year-old male referred to us
with progressively increasing multiple subcutaneous nodular lesions over his left
leg and foot, reported elsewhere as a spindle cell rhabdomyosarcoma. On review,
microscopy showed a cellular tumor comprising plump spindle cells arranged in
loose fascicles with interspersed inflammatory cells. Tumor cells exhibited mild
nuclear variation. Immunohistochemically, tumor cells expressed AE1/AE3, CD31,
Fli-1, and smooth muscle actin (SMA), confirming diagnosis of PHE. Whole-body
positron emission tomography-computed tomography (PET-CT) scan revealed multiple,
metabolically active, subcutaneous nodular lesions over the left lower leg and in
the distal tibia. Subsequently, resection specimens from the various lesions and
bone curettage also revealed features of PHE. Three months later, the patient
developed multiple lesions over his fourth toe and left foot, for which he
underwent tumor resections. At present, he is disease-free. PHE is a locally
aggressive soft tissue tumor characterized by multifocality, rarely bony
involvement and can be misdiagnosed as a high-grade sarcoma.
PMID- 27510686
TI - Vulvar granular cell tumor.
AB - Granular cell tumors (GCTs) are rare and approximately half of the all lesions
arise from head and neck, especially from the tongue. However, they are rarely
seen in the vulva. They can occur in patients of any age, but peak age incidence
is in the fourth to sixth decades. They generally occur as small, slow growing,
and skin-colored nodule. GCTs are usually benign, but malignant cases were
reported. Recurrence can be seen in benign tumors with clear margins, but rates
increase with positive margins. The treatment is complete surgical excision. We
report a case of benign GCT of the vulva. A 41-year-old patient presented with
vulvar mass, and biopsy was consisted with GCT.
PMID- 27510685
TI - Primary intraosseous atypical inflammatory meningioma presenting as a lytic skull
lesion: Case report with review of literature.
AB - Primary extradural meningiomas of the skull comprise 1% of all meningiomas, and
lytic skull meningiomas are still rarer and are said to be more aggressive. We
present a case of 38-year-old male with an extradural tumor which on
histopathological examination showed features of inflammatory atypical meningioma
(WHO Grade II). The intense inflammatory nature of osteolytic primary
intraosseous meningioma has not been reported before. This entity deserves
special mention because of the need for adjuvant therapy and proper follow-up.
PMID- 27510687
TI - Recurrent multifocal cutaneous Kaposiform hemangioendothelioma: A rare vascular
tumor of infancy and childhood.
AB - Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor of
childhood although cases occurring in adulthood are also described. The features
overlap with juvenile capillary hemangioma and Kaposi sarcoma. We report a rare
case of recurrent, multifocal (nose and chin) cutaneous KHE initially occurring
in a 3-year-old female child, uncomplicated by Kasabach-Merritt syndrome.
Recurrences occurred over the next 6 years and resulted in complete distortion of
the nose, requiring plastic repair.
PMID- 27510688
TI - Unusual ganglioglioma with extensive calcification and ossification.
AB - Ganglioglioma is a slow-growing relatively low-grade mixed glioneuronal tumor
with most cases corresponding to the WHO Grade I category. It frequently presents
with seizures. The temporal lobe is the most common location followed by frontal,
parietal, and occipital lobes. These generally behave in a benign fashion and
have a favorable prognosis. We describe a case of a 24-year-old male presenting
with convulsions and a calcified parieto-occipital mass. This mass removed from
the parietal lobe showed neoplastic glial and dysplastic neuronal tissue amidst
extensive areas of calcification and foci of ossification. On
immunohistochemistry, the glial component expressed glial fibrillary acidic
protein whereas the dysplastic neuronal component expressed synaptophysin and
CD34. Epithelial membrane antigen was negative and Ki-67 showed a low
proliferative index. After the surgery, the patient is free of neurological
symptoms. Widespread calcification and ossification are very unusual in
ganglioglioma, which prompted us to report this case.
PMID- 27510689
TI - Pulmonary hemangioendothelioma with osteoclast-like giant cells: A rare
observation.
AB - Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular neoplasm,
predominantly encountered in women, more often in the age group of 40 years and
below. It is a tumor of borderline malignant potential with a clinical course
intermediate between hemangioma and angiosarcoma. The tumor has variable
prognosis, and treatment options include surgical excision in operable cases and
chemotherapy in disseminated ones. The present report describes complete
clinical, radiological, and histopathological features of PEH with osteoclast
like giant cells and metaplastic ossification in a 20-year-old boy who presented
with dyspnea and episodes of hemoptysis with review of literature.
PMID- 27510690
TI - Fine-needle aspiration cytology of isolated skull nodule: Unfolding the clinical
spectrum.
AB - Follicular thyroid carcinoma (FTC) has been classified as either minimally
invasive or widely invasive carcinoma and shows a propensity for blood-borne
metastasis. Most common sites of metastasis are lung and bone followed by brain,
liver, and skin. Minimally invasive FTC (MIFTC) is characterized by limited
capsular and/or vascular invasion with good long-term outcomes, some cases of
which show a poor prognosis because of severe distant metastasis. Skull
metastasis in adults commonly arises from the lung, breast, and prostate and
uncommonly from the thyroid. In our case, fine-needle aspiration cytology of
isolated skull nodule was a reliable tool in the diagnosis of metastasis and
suggesting the primary in thyroid thereby prompting early workup of a patient.
The case is unique since it represents the rare disseminated metastasis from
MIFTC with incomplete capsular penetration alone without angioinvasion that can
behave as aggressively as a widely invasive FTC.
PMID- 27510691
TI - Adenocarcinoma of the anal canal: A report of two cases with review of
literature.
AB - Adenocarcinoma of the anal canal accounts for about 20% of all anal canal
cancers. It is subclassified into two types. (1) Colorectal type, which arises
from the mucosa above dentate line and (2) extramucosal type, which includes
adenocarcinoma arising in anorectal fistulae and adenocarcinoma arising from anal
glands. Anal gland adenocarcinomas are extremely rare. In this article, we
present two cases of anal adenocarcinoma, one colorectal type, and other anal
gland carcinoma along with review of literature.
PMID- 27510692
TI - 'Childhood systemic mastocytosis associated with t (8; 21) (q22; q22) acute
myeloid leukemia'.
AB - Systemic mastocytosis (SM) with associated clonal nonmast cell lineage disease is
seen in up to 20% cases of SM. SM is uncommon in the pediatric population. T (8;
21) (q22; q22) is a good prognostic factor in acute myeloid leukemia (AML).
However, the presence of SM confers poor prognosis in t (8; 21) (q22; q22)
associated AML. We report the case of a child with t (8; 21) (q22; q22)
associated AML with SM and her minimal residual disease status over the course of
her treatment. In our case, the abnormal mast cells, showing co-expression of
CD25 and CD2, persisted even after the marrow showed no evidence of residual AML.
PMID- 27510693
TI - Lymphoblastic leukemia with surface light chain restriction: A diagnostic
dilemma.
AB - Surface light chain expression is a feature of mature B-cell neoplasms. Light
chain restriction in precursor B acute lymphoblastic leukemia is infrequently
seen. We report a case of a 28-year-old female with non-FAB L3 morphology blasts
and immunophenotypic features showing overlap between a precursor and mature B
cell neoplasm.
PMID- 27510694
TI - Early cirrhosis in a young female with protein C deficiency: An extremely unusual
case report with review.
AB - Protein C deficiency is a well recognized risk factor for development of venous
thromboembolism but has never been reported to be associated with development of
liver cirrhosis .We report a case of a 26 years old female who presented with
multiple thrombosis involving superior mesenteric vein ,main portal vein and
multiple cerebral veins. Liver biopsy done was reported as cirrhosis possibly due
to Wilson's disease. However no improvement was seen with D penicillamine and
patient's condition detiorated. Further, work up of patient revealed absence of
Protein C levels in the plasma. So finally the case was diagnosed as Cirrhosis
liver with Protein C deficiency as the likely etiology. We conclude that Protein
C deficiency should be investigated in patients with cirrhosis with thrombotic
lesions of unknown etiology.
PMID- 27510695
TI - Neurological melioidosis presenting as intracranial abscess.
AB - Melioidosis is an emerging disease in our country caused by the bacteria
Burkholderia pseudomallei. Melioidosis can virtually affect any organ. It has
varying clinical presentations ranging from pneumonia to fatal sepsis. Central
nervous system (CNS) involvement in melioidosis is rare. We present a case of CNS
melioidosis from South India. As the incidence of diabetes is increasing in our
country varying manifestations of melioidosis will be seen in routine clinical
practice. Melioidosis should be considered in the differential diagnosis of
intracranial abscess and meningoencephalitis, especially in diabetics.
PMID- 27510696
TI - Extended spectrum beta-lactamase producing Shigella flexneri serotype-2 causing
bacteremia in a patient with uncontrolled diabetes mellitus.
AB - We report a case of Shigella flexneri serotype-2 causing bacteremia in an elderly
gentleman with uncontrolled diabetes mellitus, who had no other apparent risk
factors. Antibiotic susceptibility testing revealed that the organism was a
multidrug resistant extended spectrum beta-lactamase producing straian, which was
confirmed by molecular characterization. This rare case alerts both the clinician
and microbiologist to a previously unaddressed risk factor of Shigella spp.
causing bacteremia, as well as emerging resistant strains that are on the rise in
immunocompromised patients.
PMID- 27510697
TI - Maculopapular rash presentation of febrile illness in an adult with Varicella
zoster virus infection.
AB - Varicella zoster usually manifests as maculopapular rash (MPR), which later
progresses to vesicle. It can also manifest as MPR without progression to the
vesicle stage. This atypical manifestation is more common in adults and
immunocompromised patients. A 30-year-old female presented with high-grade fever
and rash over face and body for 5 days. She was diagnosed to have Varicella
zoster virus (VZV) infection by positive VZV immunoglobulin M enzyme-linked
immunosorbent assay and polymerase chain reaction. We present this case to
increase awareness among clinicians on the atypical manifestations of VZV and
prevent complications by early diagnosis.
PMID- 27510698
TI - Clear cell metaplasia of the prostatic urethra.
PMID- 27510699
TI - Concomitant occurrence of multiple myeloma with diffuse large B-cell lymphoma.
PMID- 27510700
TI - Comparison of carbapenem breakpoints in Clinical Laboratory Standard Institute
and European Committee on Antimicrobial Susceptibility Testing guidelines on
antibiotic susceptibility test reporting of Acinetobacter baumannii.
PMID- 27510701
TI - Undergraduate medical students' perspectives on objective structured practical
examination in Pathology.
PMID- 27510702
TI - Salivary gland anlage tumor.
PMID- 27510703
TI - Issue Cover (September 2016).
AB - Cover legend: Macrophages phagocytosing RFP-labeled E.coli. GFP-APPL2 labels the
phagosomal membrane. Image produced by N. Condon. See Yeo et al. Traffic 2016;
17(9):1014-1026. Read the full article on doi:10.1111/tra.12415.
PMID- 27510704
TI - Atrial natriuretic peptide induces peroxisome proliferator activated receptor
gamma during cardiac ischemia-reperfusion in swine heart.
AB - OBJECTIVES: Atrial natriuretic peptide is a cardiac atrium-derived hormone and
its cardioprotective effects have recently been confirmed, but the actual
mechanism underlying these effects has not been well elucidated. In this study,
we proposed that atrial natriuretic peptide achieves its effects in part via
peroxisome proliferator activated receptor gamma, a nuclear receptor. METHODS:
Hemodynamic data in swine heart ischemia-reperfusion model were measured under
the conditions of no medication for control (Group N, n = 8) or that of
carperitide (synthetic human atrial natriuretic peptide) systemic administration
(Group A, n = 8). After 30 min of left anterior descending artery total occlusion
and 4 h of reperfusion, peroxisome proliferator activated receptor gamma mRNA and
protein expressions in cardiac muscle were examined. The mRNA expression of Liver
X receptor alpha, the downstream agent of peroxisome proliferator activated
receptor gamma, was also evaluated. Creatine kinase-myocardial band and Troponin
T elevations after reperfusion were evaluated as markers of cardiac damage.
RESULTS: The dP/dT decrease during reperfusion was ameliorated in Group A.
Peroxisome proliferator activated receptor gamma mRNA expression in Group A was
significantly higher in ischemic area than that in Group N, although the
difference was not significant in the marginal and non-ischemic areas. The
peroxisome proliferator activated receptor gamma protein expression in ischemic
area was also significantly dominant in Group A. CONCLUSIONS: Atrial natriuretic
peptide may achieve its cardioprotective effects in part via the activation of
the peroxisome proliferator activated receptor gamma pathway, particularly in
central areas of ischemic lesions.
PMID- 27510705
TI - Thoracoscopic pulmonary wedge resection without post-operative chest drain: an
observational study.
AB - OBJECTIVE: Chest drains are used routinely after wedge resection by video
assisted thoracoscopic surgery (VATS), although this practice is based largely on
tradition rather than evidence. Chest drains may furthermore cause pain,
infections, and prolonged length of stay. The aim of this prospective
observational study was to assess the feasibility of avoiding chest drains
following VATS wedge resection for pulmonary nodules. METHODS: Between 1 February
and 25 August 2015 166 consecutive patients planned for VATS wedge resection of
pulmonary nodules were screened for inclusion using the following criteria:
Forced expiratory volume in 1 s (FEV1) >=60 % of expected, FEV1/forced vital
capacity >=70 %, tumour diameter <=2 cm, distance from tumour to visceral pleura
<=3 cm, <=2 separate wedges, no air leak on an intraoperative air leakage test
and absence of severe adhesions, bullous/emphysematous disease, pleural effusion
and coagulopathy. Chest X-rays were done twice on the day of surgery. 30-day
complications were compiled from patient records. RESULTS: 49 patients underwent
51 unilateral VATS wedge resections without using a post-operative chest drain.
No patient required reinsertion of a chest drain. 30 (59 %) patients had a
pneumothorax of mean size 12 +/- 12 mm on supine 8-h post-operative X-ray for
which the majority resolved spontaneously within 2-week control. There were no
complications on 30-day follow-up. Median length of stay was 1 day. CONCLUSIONS:
The results support that VATS wedge resection for pulmonary nodules without a
post-operative chest drain may be safe in a selected group of patients.
PMID- 27510706
TI - Frequency of colonic adenomatous polyps in a tertiary hospital in Mumbai.
AB - INTRODUCTION: Incidence of colorectal carcinoma is increasing all over world.
There is limited data on colorectal polyps from India. We evaluated the
histomorphological features of colorectal polyps and determined risk
stratification in adenomatous polyps. METHODS: In 4970 consecutive colonoscopies,
colorectal polyps were detected in 515 cases (10.3 %). Polyps were classified
using standard histological criteria. Each polyp was evaluated for presence of
dysplasia. Adenomatous polyps were classified as low-risk adenomas (1-2 tubular
adenomas <10 mm) and high-risk adenomas characterized by villous histology, high
grade dysplasia, size >=10 mm, or >=3 adenomas. RESULTS: Of 515 colorectal
polyps, 270 (52.4 %) were adenomatous, followed by 78 (15.1 %) inflammatory, 78
(15.1 %) hyperplastic, 32 (6.2 %) hamartomatous polyps, 25 (4.8 %) benign
epithelial polyps, 5 (0.9 %) cap polyps, 5 (0.9 %) lipomatous polyps, 3 (0.5 %)
angiomatous polyps, 4 (0.7 %) lymphoid, and 15 (2.9 %) cases with adenocarcinoma
masquerading as polyps. Mean (SD) age with colorectal polyps was 54.8 (33.0)
years while for adenomatous polyps, 59.5 (14.8) years with male to female ratio
of 2:1. Majority of adenomatous polyps 124 (45.9 %) were tubular adenomas present
in rectosigmoid. High-grade dysplasia was found in 38 (14 %) adenomas. One
hundred and fifty-five (57.4 %) were high risk of which majority were villous
adenomas and nine (7.2 %) tubular adenomas. CONCLUSION: The most common
colorectal polyps found during routine colonoscopy were 270 adenomatous (52.4 %)
cases. Of these, 155 (57.4 %) adenomatous polyps were high-risk category.
Population prevalence data of colonic polyps in general population beyond the age
of 50 years needs to be obtained.
PMID- 27510707
TI - Multivariable predictors of substantial blood loss in children undergoing
craniosynostosis repair: implications for risk stratification.
AB - BACKGROUND: Operative treatment of craniosynostosis is associated with
substantial blood loss, often requiring transfusion of packed red blood cells
(PRBC) and coagulation products. AIMS: The aim of this prospective study was to
analyze thromboelastographic (TEG) parameters and platelet fibrinogen product to
determine predictors of substantial blood loss, and the need for PRBC transfusion
and coagulation products. METHODS: With IRB approval, we enrolled 120 children
undergoing craniosynostosis repair with a standardized anesthetic, fluid
management, and TEG measurements at predefined times. Outcomes of interest were
intraoperative blood loss, and need for PRBC transfusion and coagulation
products. Multivariable logistic regression and receiver operating characteristic
(ROC) curve analysis was applied to determine independent predictors of
substantial blood loss and need for coagulation products. RESULTS: One hundred
and eighteen children were included in the analysis. Forty-four required PRBC
transfusion (median 26 ml.kg(-1) ; IQR: 22-42) with median blood loss of 56
ml.kg(-1) (IQR: 43-83). Factors associated with the PRBC transfusion included
type of surgery, duration of surgery, and three TEG parameters, alpha-angle, MA,
and K-time (all P < 0.001). A predictive algorithm was developed by subgroup
analysis of cranial vault reconstruction (CVR) patients for substantial
intraoperative blood loss (defined as >=60 ml.kg(-1) ) and need for coagulation
products with ROC-derived cut-off values: platelet fibrinogen product, <343;
alpha-angle, <62 degrees ; MA, <55 mm; K-time, >2.1 min. The best prognostic
combination included at least two of these four predictors (sensitivity 89%,
specificity 90%). Multivariable regression identified MA as the only independent
predictor of coagulation product administration (P < 0.001) and ROC analysis
identified MA <46 mm as the optimal cut-off (sensitivity 86%, specificity 94%).
CONCLUSIONS: Risk for substantial intraoperative blood loss can be assessed using
TEG parameters and platelet fibrinogen product, whereas the need for coagulation
products is strongly related to low MA. Patients susceptible to substantial blood
loss can be risk stratified based on their TEG/platelet fibrinogen product
profile.
PMID- 27510708
TI - A war psychiatry approach to warfare in the Middle Byzantine period.
AB - Combat stress cases were traced in historical texts and military manuals on
warfare from the Middle Byzantine period; they were mainly labelled as cowardice.
Soldiers suffered from nostalgia or exhaustion; officers looked stunned, or could
not speak during the battle. Cruel punishments were often enforced. Suicide and
alcohol abuse were rarely mentioned. The Byzantines' evacuation system for battle
casualties was well organized. Psychological operations were conducted and
prisoners-of-war were usually part of them. The Byzantine army had
'parakletores', officers assigned to encourage soldiers before combat. The
leaders dealt with combat stress by using their rhetoric skills and emphasizing
religious faith in eternal life. The treatment of the 'cowards' was rather
similar to modern war psychiatry principles of treatment. No description of PTSD
was found.
PMID- 27510709
TI - Erratum to: Practical impacts of genomic data "cleaning" on biological discovery
using surrogate variable analysis.
PMID- 27510711
TI - Role of let-7b/Fzd4 axis in mitochondrial biogenesis through wnt signaling: In
neonatal and adult megakaryocytes.
AB - BACKGROUND: Megakaryocytes (MKs), a rare population of bone marrow cells, are
responsible for the production of platelets. Sick neonates are predisposed to
developing thrombocytopenia (platelet count <150*109/L) and neonates are affected
by several megakaryocyte disorders as compared to adults. HYPOTHESIS: MicroRNAs
(miRNAs) have been shown to crucially involve in the regulation of stem-cell
differentiation in normal as well as malignant hematopoiesis, but their role in
regulation of biological differences between adult and neonatal megakaryopoiesis
is unknown. METHODS: To study this, we cultured human cord blood (CB) and
peripheral blood (PB) derived CD34+ cells in the presence of thrombopoietin for
14days and collected cultures expressing>90% CD41+ by flow cytometry and studied
88 miRNAs involved in stem cell development and differentiation. miRNA validation
studies were performed in Dami cell line. RESULTS: Out of 88 miRNAs involved in
stem cell development, let-7b was the only miRNA down regulated (~10-fold) in
neonates compared to adult-MKs. Let-7b has not been previously described in MKs,
however reduced expression of let-7b was found in several human cancers,
suggesting that it functions as a tumor suppressor. Our results showed the
inhibitory effect of let-7b on wnt signaling pathway by regulating Fzd4 (frizzled
family receptor 4) and thereby regulating proliferation as well as
differentiation. Let-7b down regulation induced mitochondrial biogenesis and its
markers PGC-1alpha and NRF1 during megakaryocyte development. CONCLUSIONS: Our
findings for the first time unveil the novel role of let-7b/Fzd4 axis through wnt
signaling by regulating mitochondrial biogenesis during megakaryocyte
development.
PMID- 27510710
TI - Evaluation of artificial selection in Standard Poodles using whole-genome
sequencing.
AB - Identifying regions of artificial selection within dog breeds may provide
insights into genetic variation that underlies breed-specific traits or diseases
particularly if these traits or disease predispositions are fixed within a breed.
In this study, we searched for runs of homozygosity (ROH) and calculated the d i
statistic (which is based upon F ST) to identify regions of artificial selection
in Standard Poodles using high-coverage, whole-genome sequencing data of 15
Standard Poodles and 49 dogs across seven other breeds. We identified consensus
ROH regions >=1 Mb in length and common to at least ten Standard Poodles covering
0.6 % of the genome, and d i regions that most distinguish Standard Poodles from
other breeds covering 3.7 % of the genome. Within these regions, we identified
enriched gene pathways related to olfaction, digestion, and taste, as well as
pathways related to adrenal hormone biosynthesis, T cell function, and protein
ubiquitination that could contribute to the pathogenesis of some Poodle-prevalent
autoimmune diseases. We also validated variants related to hair coat and skull
morphology that have previously been identified as being under selective pressure
in Poodles, and flagged additional polymorphisms in genes such as ITGA2B, CBX4,
and TNXB that may represent strong candidates for other common Poodle disorders.
PMID- 27510714
TI - Not "just" a shoulder dislocation.
PMID- 27510712
TI - Apoptotic signaling pathways induced by acute administration of branched-chain
amino acids in an animal model of maple syrup urine disease.
AB - Maple Syrup Urine Disease (MSUD) is an inborn error of metabolism caused by a
deficiency of the branched-chain alpha-keto acid dehydrogenase complex activity.
This blockage leads to accumulation of the branched-chain amino acids leucine,
isoleucine and valine, as well as their corresponding alpha-keto acids and alpha
hydroxy acids. The affected patients present severe neurological symptoms, such
as coma and seizures, as well as edema and cerebral atrophy. Considering that the
mechanisms of the neurological symptoms presented by MSUD patients are still
poorly understood, in this study, protein levels of apoptotic factors are
measured, such as Bcl-2, Bcl-xL, Bax, caspase-3 and -8 in hippocampus and
cerebral cortex of rats submitted to acute administration of branched-chain amino
acids during their development. The results in this study demonstrated that BCAA
acute exposure during the early postnatal period did not significantly change Bcl
2, Bcl-xL, Bax and caspase-8 protein levels. However, the Bax/Bcl-2 ratio and
procaspase-3 protein levels were decreased in hippocampus. On the other hand,
acute administration of BCAA in 30-day-old rats increase in Bax/Bcl-2 ratio
followed by an increased caspase-3 activity in cerebral cortex, whereas BCAA
induces apoptosis in hippocampus through activation and cleavage of caspase-3 and
-8 without changing the Bax/Bcl-2 ratio. In conclusion, the results suggest that
apoptosis could be of pivotal importance in the developmental neurotoxic effects
of BCAA. In addition, the current studies also suggest that multiple mechanisms
may be involved in BCAA-induced apoptosis in the cerebral cortex and hippocampus.
PMID- 27510713
TI - Behavioral effects of Citrus limon and Punica granatum combinations in rats.
AB - Dietary supplements are becoming more influential as viable treatment for common
chronic diseases and to promote normal development and functions of all system
including brain. Disorders like anxiety and depression may be managed through
healthier variations is dietary pattern, since there are indications that diet
rich in antioxidants and vitamins diminish anxiety and depression. Hence this
investigation was planned to assess the behavioral effects of Citrus limon and
Punica granatum in two combination doses i.e. 0.4 + 5 ml/kg and 0.2 + 8 ml/kg C.
limon and P. granatum respectively in rats. Antidepressant and anxiolytic effects
were explicitly judged twice during 15 days using forced swimming and open field
tests and elevated plus maze. In open field test C. limon and P. granatum showed
increase in distance travelled, number of central entries and number of rearing's
at 0.4 + 5 ml/kg combination, in the elevated plus maze, number of open arm
entries were found to be augmented and in forced swimming test, there was decline
in duration of immobility and rise in duration of climbing at both combinations
i.e. 0.4 + 5 ml/kg and 0.2 + 8 ml/kg C. limon and P. granatum. These results
suggest that C. limon and P. granatum at 0.4 + 5 ml/kg combination have
anxiolytic and antidepressant effect.
PMID- 27510715
TI - Algorithmic Approach With Clinical Pathology Consultation Improves Access to
Specialty Care for Patients With Systemic Lupus Erythematosus.
AB - OBJECTIVES: Harris Health System (HHS) is a safety net system providing health
care to the underserved of Harris County, Texas. There was a 6-month waiting
period for a rheumatologist consult for patients with suspected systemic lupus
erythematosus (SLE). The objective of the intervention was to improve access to
specialty care. METHODS: An algorithmic approach to testing for SLE was
implemented initially through the HHS referral center. The algorithm was further
offered as a "one-click" order for physicians, with automated reflex testing,
interpretation, and case triaging by clinical pathology. RESULTS: Data review
revealed that prior to the intervention, 80% of patients did not have complete
laboratory workups available at the first rheumatology visit. Implementation of
algorithmic testing and triaging of referrals by pathologists resulted in
decreasing the waiting time for a rheumatologist by 50%. CONCLUSIONS: Clinical
pathology intervention and case triaging can improve access to care in a county
health care system.
PMID- 27510716
TI - An Assessment of the State of Current Practice in Coagulation Laboratories.
AB - OBJECTIVES: To assess the state of current practice in coagulation laboratories
regarding three pressing issues: staffing, handling Ebola specimens, and
testing/billing for tests that measure direct oral anticoagulants (DOAC).
METHODS: A survey and analysis of specialized coagulation laboratories in North
America was conducted. RESULTS: Approximately 4,000 special coagulation tests-per
technologist-per-year was rated as either a "good" staffing level or "adequate
but-ideally-need-more" employees. Requiring technologists to perform more than
that was rated as an "inadequate" staffing level. For Ebola patients, coagulation
testing is mostly performed by point-of-care. Only 26.1% would perform
coagulation tests for Ebola specimens within their laboratory (rather than at the
bed side or a separate designated space outside the laboratory). Coagulation
tests offered for Ebola patients were limited: prothrombin time (63.0% of
laboratories), activated partial thromboplastin time (37.0%), D-dimer (13.0%),
and fibrinogen (8.7%); 26.1% of laboratories did not offer any coagulation tests
for Ebola patients. Approximately 35% of special coagulation laboratories bill
for at least one laboratory test for DOACs: 33% bill for an anti-Xa calibrated
with rivaroxaban, 17% bill for an anti-Xa calibrated with apixaban, and 27% bill
for at least one of several tests for dabigatran. Approximately 48% do not offer
any tests for DOACs. CONCLUSIONS: These results may help laboratories negotiate
for additional technologists if needed, prepare for Ebola specimens, and manage
the demand for laboratory tests for new DOAC anticoagulants.
PMID- 27510717
TI - Opportunities for Improvement in Pathology Reporting of Childhood
Nonrhabdomyosarcoma Soft Tissue Sarcomas: A Report From Children's Oncology
Group (COG) Study ARST0332.
AB - OBJECTIVES: Treatment of soft tissue tumors in young patients relies on the
diagnostic information conveyed in the pathology report. We examined pathology
reports from Children's Oncology Group ARST0332 for inclusion of data elements
required in published guidelines. METHODS: Pathology reports for 551 eligible
patients were examined for required data elements defined by the College of
American Pathologists, including tissue type, procedure, tumor site, tumor
maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate,
extent of necrosis, tumor grade, margin status, use of ancillary studies, and
pathologic stage. RESULTS: Only 65 (12%) of 551 reports included all required
data elements. Of reports containing synoptic templates, 57% were complete.
CONCLUSIONS: This study reveals significant opportunity to improve the quality of
pathology reports in young patients with soft tissue tumors. Use of templates or
checklists improves completeness of reports.
PMID- 27510718
TI - Massive Transfusion Protocol: Communication Ordering Practice Survey (MTP COPS).
AB - OBJECTIVES: We sought to assess ordering practices and quality of communication
during massive transfusion at US level I trauma centers. METHODS: An anonymous,
web-based survey was distributed to blood banks supporting US level I trauma
centers. Information gathered in the survey included demographics, utilization of
and perceived level of support for computerized physician order entry (CPOE),
frequency of order confusion, and nonprotocol ordering. Responses were analyzed
using descriptive statistics. RESULTS: Responses were received from 43 of 121
centers (35.5% response rate), with the majority completed by blood bank
physicians (67.4%) and blood bank supervisors (25.6%). Allowable pathways for
massive transfusion protocol (MTP) ordering included CPOE (48.8%),
verbal/telephone (86.1%), and written (44.2%). The preferred method of MTP
activation was verbal/telephone (86.1%). Initial activation of MTP was well
communicated (97.6% agreement), but confusion associated with ongoing needs was
reported to occur at least sometimes by 32.6%. CONCLUSIONS: Although CPOE-based
MTP ordering is offered by nearly half of US level I trauma centers,
verbal/telephone ordering is by far the preferred mechanism. Our survey
identifies confusion surrounding blood component needs during MTP resuscitation
as an opportunity for practice improvement.
PMID- 27510719
TI - The Faith of Sacrifice: Leadership Trade-Offs in an Afro-Brazilian Religion.
AB - Despite secular trends in some countries, prestige-based authority in the form of
religious leadership remains hugely influential in the everyday lives of millions
of people around the world. Here, the costs and benefits of religious leadership
are explored in an urban setting in northeastern Brazil. An economic game, within
group cooperation questionnaires, and social network analyses were carried out
among adherents of an Afro-Brazilian religion. Results reveal that leaders
display high levels of religious commitment and disproportionally provide
cooperative services to group members. On the other hand, initiates cooperate
less than leaders but do not differ in levels of received cooperation or social
cohesion measures. This may indicate some level of exploitation or free-riding.
Demographic and group variables also appear to play an important role in the
degree of social cohesion a group achieves. These findings are discussed in the
context of non-Western urban settings where religious leadership may represent
both an alternative to social advancement and a crucial source of material aid,
social support, and a strong sense of community.
PMID- 27510720
TI - Size Effects on the Interaction of QDs with the Mitochondrial Membrane In Vitro.
AB - The mitochondrial toxicity induced by GSH-CdTe Quantum dots (QDs) of different
sizes was investigated. The decreases in absorbance and transmission electron
microscopy images show that QDs induce the swelling of mitochondria. Results of
flow cytometry indicate that QDs cause a reduction of mitochondrial membrane
potential (MMP). A remarkable increase in fluidity of protein regions of
mitochondrial membrane is observed, whereas the lipid regions are not obviously
affected. Cyclosporin A (CsA) effectively prevents the QD-induced mitochondrial
swelling. On the basis of these results, it is proposed that QDs induce
mitochondrial permeability transition (MPT). Moreover, with increasing QDs size,
a pronounced MPT is observed. The difference between the membrane fluidity
induced by QDs and Cadmium ion and the ineffective protective effects of EDTA
suggests that the mitochondrial toxicity of QDs cannot be only attributed to the
release of metal ion. The protective effects of HSA indicate that the interaction
of QDs with pore-forming protein gives rise to the increase in membrane fluidity.
This hypothesis is demonstrated by the interaction of QDs with model membranes
and proteins using differential scanning calorimetry and isothermal titration
microcalorimetry. In conclusion, as the size of QDs increases, the binding
affinity of QDs with membrane protein increases, and therefore causes a
pronounced mitochondrial damage.
PMID- 27510722
TI - Website aims to help people understand health research.
PMID- 27510721
TI - Cost Effectiveness of Pneumococcal Vaccination in Children in Low- and Middle
Income Countries: A Systematic Review.
AB - BACKGROUND: Although pneumococcal conjugate vaccines (PCVs) have been available
for prevention of invasive pneumococcal disease (IPD) caused by Streptococcus
pneumoniae (S. pneumoniae) for over a decade, their adoption into national
immunization programmes in low- and middle-income countries (LMICs) is still
limited. Economic evaluations (EEs) play a crucial role in support of evidence
informed decisions. OBJECTIVE: This systematic review aims to provide a critical
summary of EEs of PCVs and identify key drivers of EE findings in LMICs. METHODS:
We searched Scopus, ISI Web of Science, PubMed, Embase and Cochrane Central from
their inception to 30 September 2015 and limited the search to LMICs. The search
was undertaken using the search strings 'pneumococc* AND conjugat* AND (vaccin*
OR immun*)' AND 'economic OR cost-effectiveness OR cost-benefit OR cost-utility
OR cost-effectiveness OR cost-benefit OR cost-utility' in the abstract, title or
keyword fields. To be included, each study had to be a full EE of a PCV and
conducted for an LMIC. Studies were extracted and reviewed by two authors. The
review involved standard extraction of the study overview or the characteristics
of the study, key drivers or parameters of the EE, assumptions behind the
analyses and major areas of uncertainty. RESULTS: Out of 134 records identified,
22 articles were included. Seven studies used a Markov model for analysis, while
15 studies used a decision-tree analytic model. Eighteen studies performed a cost
utility analysis (CUA), with disability-adjusted life-years, quality-adjusted
life-years or life-years gained as a measure of health outcome, while four
studies focused only on cost-effectiveness analysis (CEA). Both CEA and CUA
findings were provided by eight studies. Herd effects and serotype replacement
were considered in 10 and 13 studies, respectively. The current evidence shows
that both the 10-valent and 13-valent PCVs are probably cost effective in
comparison with the 7-valent PCV or no vaccination. The most influential
parameters were vaccine efficacy and coverage (in 16 of 22 studies), vaccine
price (in 13 of 22 studies), disease incidence (in 11 of 22 studies), mortality
from IPD and pneumonia (in 8 of 22 studies) and herd effects (in 4 of 22
studies). The findings were found to be supportive of the products owned by the
manufacturers. CONCLUSION: Our review demonstrated that an infant PCV programme
was a cost-effective intervention in most LMICs (in 20 of 22 studies included).
The results were sensitive to vaccine efficacy, price, burden of disease and
sponsorship. Decision makers should consider EE findings and affordability before
adoption of PCVs.
PMID- 27510723
TI - Signaling pathways coordinating the alkaline pH response confer resistance to the
hevein-type plant antimicrobial peptide Pn-AMP1 in Saccharomyces cerevisiae.
AB - MAIN CONCLUSION: Genome-wide screening of Saccharomyces cerevisiae revealed that
signaling pathways related to the alkaline pH stress contribute to resistance to
plant antimicrobial peptide, Pn-AMP1. Plant antimicrobial peptides (AMPs) are
considered to be promising candidates for controlling phytopathogens. Pn-AMP1 is
a hevein-type plant AMP that shows potent and broad-spectrum antifungal activity.
Genome-wide chemogenomic screening was performed using heterozygous and
homozygous diploid deletion pools of Saccharomyces cerevisiae as a chemogenetic
model system to identify genes whose deletion conferred enhanced sensitivity to
Pn-AMP1. This assay identified 44 deletion strains with fitness defects in the
presence of Pn-AMP1. Strong fitness defects were observed in strains with
deletions of genes encoding components of several pathways and complex known to
participate in the adaptive response to alkaline pH stress, including the cell
wall integrity (CWI), calcineurin/Crz1, Rim101, SNF1 pathways and endosomal
sorting complex required for transport (ESCRT complex). Gene ontology (GO)
enrichment analysis of these genes revealed that the most highly overrepresented
GO term was "cellular response to alkaline pH". We found that 32 of the 44
deletion strains tested (72 %) showed significant growth defects compared with
their wild type at alkaline pH. Furthermore, 9 deletion strains (20 %) exhibited
enhanced sensitivity to Pn-AMP1 at ambient pH compared to acidic pH. Although
several hundred plant AMPs have been reported, their modes of action remain
largely uncharacterized. This study demonstrates that the signaling pathways that
coordinate the adaptive response to alkaline pH also confer resistance to a
hevein-type plant AMP in S. cerevisiae. Our findings have broad implications for
the design of novel and potent antifungal agents.
PMID- 27510724
TI - Two-Dimensional Infrared Study of Vibrational Coupling between Azide and Nitrile
Reporters in a RNA Nucleoside.
AB - The vibrations in the azide, N3, asymmetric stretching region and nitrile, CN,
symmetric stretching region of 2'-azido-5-cyano-2'-deoxyuridine (N3CNdU) are
examined by two-dimensional infrared (2D IR) spectroscopy. At earlier waiting
times, the 2D IR spectrum shows the presence of both vibrational transitions
along the diagonal and off-diagonal cross peaks indicating vibrational coupling.
The coupling strength is determined from the off-diagonal anharmonicity to be 66
cm(-1) for the intramolecular distance of ~7.9 A, based on a structural map
generated for this model system. In addition, the frequency-frequency correlation
decay is detected, monitoring the solvent dynamics around each individual probe
position. Overall, these vibrational reporters can be utilized in tandem to
simultaneously track global structural information and fast structural
fluctuations.
PMID- 27510725
TI - Effect of Three Statins on Glucose Uptake of Cardiomyocytes and its Mechanism.
AB - BACKGROUND The aim of this study was to investigate the effects of different
statins on glucose uptake and to confirm its mechanism in primary cultured rat
cardiomyocytes after administration of atorvastatin, pravastatin, and
rosuvastatin. MATERIAL AND METHODS Primary cultured rat cardiomyocytes were
randomly assigned to 5 groups: normal control group (OB), insulin group (S1),
statin 1-MUM (S2), 5-MUM (S3), and 10-MUM (S4) groups for 3 different statins.
The 2-[3H]-DG uptake of each group was determined and the mRNA and protein
expression levels of glucose transporter type 4 (GLUT4), insulin receptor
substrate (IRs), and RhoA were assessed. RESULTS After treatment with different
concentrations of statins and insulin, the 2-[3H]-DG uptake showed a significant
negative correlation with the concentration of atorvastatin (P<0.05), and no
significant correlation with pravastatin and rosuvastatin. The mRNA and protein
expression levels of GLUT4 and IRs-1 in primary cultured cardiomyocytes were both
significantly reduced by atorvastatin treatment (P<0.05). Pravastatin and
rosuvastatin showed no significant effects on GLUT4 and IRs-1 expression. The
mRNA and protein expression levels of RhoA both showed no significant difference
when treated with the 3 statins. CONCLUSIONS These results confirm that
atorvastatin can inhibit insulin-induced glucose uptake in primary cultured rat
cardiomyocytes by regulating the PI3K/Akt insulin signal transduction pathway.
PMID- 27510726
TI - Phase II trial of pegylated interferon alfa-2b in young patients with
neurofibromatosis type 1 and unresectable plexiform neurofibromas.
AB - Background: There is no proven medical therapy for plexiform neurofibromas (PNs).
We undertook a phase II trial of pegylated interferon (PI) to evaluate response
and time to progression (TTP). Methods: PI was administered as a subcutaneous
injection to patients with neurofibromatosis type 1-related PN, stratified by the
presence of symptoms (asymptomatic: stratum 1, symptomatic: stratum 2) or
documented imaging progression (stratum 3). Patients in strata 1 and 2 received
PI for up to one year if stable, 2 years for those with clinical (stratum 2) or
imaging response (>=20% decrease in volume). Patients on stratum 3 continued PI
until progression. PI was considered active in stratum 3 if TTP doubled compared
with the placebo arm of a previous randomized trial using tipifarnib. Results:
Enrolled were 82 evaluable patients (median age 10 y; range 1.6 to 21.4). Fatigue
and/or worsening of behavioral issues were the most common toxicities requiring
dose modification. Across all strata, imaging responses were seen in 4 patients
(5%). Three of 26 symptomatic patients on stratum 2 met the criteria for clinical
response without corresponding imaging changes. In stratum 3, median TTP was 29.4
months versus 11.8 for the placebo arm of the previous trial (P=.031). The slope
of tumor growth on PI slowed significantly compared with the slope before
starting PI (P=.044). Conclusions: In patients with active PN, PI results in more
than doubling of the TTP compared with placebo. Imaging changes in symptomatic
patients were not associated with changes in clinical status.
PMID- 27510727
TI - A Novel Nitrobenzoate Microtubule Inhibitor that Overcomes Multidrug Resistance
Exhibits Antitumor Activity.
AB - Multidrug resistance is a major limitation for microtubule-binding agents in
cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl
5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity
against multidrug-resistant cell lines and its antitumor efficacy in animal
models. IMB5046 disrupted microtubule structures in cells and inhibited purified
tubulin polymerization in vitro. It bound to the colchicine pocket of tubulin.
IMB5046 displayed potent cytotoxicity against multiple tumor cell lines with an
IC50 range of 0.037-0.426 MUM. Notably, several multidrug-resistant cell lines
which were resistant to colchicine, vincristine and paclitaxel remained sensitive
to IMB5046. IMB5046 was not a P-glycoprotein substrate. IMB5046 blocked cell
cycle at G2/M phase and induced cell apoptosis. Microarray assay indicated that
the differentially expressed genes after IMB5046 treatment were highly related to
immune system, cell death and cancer. In a mouse xenograft model IMB5046
inhibited the growth of human lung tumor xenograft by 83% at a well-tolerated
dose. It is concluded that IMB5046 is a tubulin polymerization inhibitor with
novel chemical structure and can overcome multidrug resistance. It is a promising
lead compound for cancer chemotherapy, especially for treatment of multidrug
resistant tumors.
PMID- 27510729
TI - Structural entropy of glassy systems from graph isomorphism.
AB - Configurational entropy plays a central role in thermodynamic scenarios of the
glass transition. As a measure of the number of basins in the potential energy
landscape, configurational entropy for a glass-forming liquid can be evaluated by
explicitly counting distinct inherent structures. In this work, we propose a
graph-theory based method to examine local structure and obtain the corresponding
entropy of hard-particle systems. Voronoi diagrams of associated clusters are
classified using a graph isomorphism algorithm. The statistics of these clusters
reveal structural motifs such as icosahedron-like order, and also allow us to
calculate the structural entropy SG. We find the structural entropy of an n
particle subsystem grows linearly with n. Thus the structural entropy per
particle can be obtained from the slope dSG/dn. Our results are consistent with
previous values for configurational entropy obtained via thermodynamic
integration. Structural entropies per particle are measured for hard-disk and
hard-sphere polydisperse systems, and extrapolated for monodisperse hard disks,
all of which are nonzero at the dynamic glass transition.
PMID- 27510728
TI - Concise Total Syntheses of (+)-Haplocidine and (+)-Haplocine via Late-Stage
Oxidation of (+)-Fendleridine Derivatives.
AB - We report the first total syntheses of (+)-haplocidine and its N1-amide congener
(+)-haplocine. Our concise synthesis of these alkaloids required the development
of a late-stage and highly selective C-H oxidation of complex aspidosperma
alkaloid derivatives. A versatile, amide-directed ortho-acetoxylation of indoline
amides enabled our implementation of a unified strategy for late-stage
diversification of hexacyclic C19-hemiaminal ether structures via oxidation of
the corresponding pentacyclic C19-iminium ions. An electrophilic amide activation
of a readily available C21-oxygenated lactam, followed by transannular
cyclization and in situ trapping of a transiently formed C19-iminium ion,
expediently provided access to hexacyclic C19-hemiaminal ether alkaloids (+)
fendleridine, (+)-acetylaspidoalbidine, and (+)-propionylaspidoalbidine. A highly
effective enzymatic resolution of a non-beta-branched primary alcohol (E = 22)
allowed rapid preparation of both enantiomeric forms of a C21-oxygenated
precursor for synthesis of these aspidosperma alkaloids. Our synthetic strategy
provides succinct access to hexacyclic aspidosperma derivatives, including the
antiproliferative alkaloid (+)-haplocidine.
PMID- 27510730
TI - Stabilisation of metastable polymorphs: the case of paracetamol form III.
AB - The design of a melt synthesis of the first air-stable formulation of the
metastable form III of paracetamol is derived from thermo-spectroscopic and
thermo-diffraction experiments. Melt crystallisation in the presence of beta-1,4
saccharides produces form III selectively and the excipients appear to act as
stabilising 'active' templates of the metastable polymorph.
PMID- 27510732
TI - Electrical Identification and Selective Microstimulation of Neuronal Compartments
Based on Features of Extracellular Action Potentials.
AB - A detailed, high-spatiotemporal-resolution characterization of neuronal responses
to local electrical fields and the capability of precise extracellular
microstimulation of selected neurons are pivotal for studying and manipulating
neuronal activity and circuits in networks and for developing neural prosthetics.
Here, we studied cultured neocortical neurons by using high-density
microelectrode arrays and optical imaging, complemented by the patch-clamp
technique, and with the aim to correlate morphological and electrical features of
neuronal compartments with their responsiveness to extracellular stimulation. We
developed strategies to electrically identify any neuron in the network, while
subcellular spatial resolution recording of extracellular action potential (AP)
traces enabled their assignment to the axon initial segment (AIS), axonal arbor
and proximal somatodendritic compartments. Stimulation at the AIS required low
voltages and provided immediate, selective and reliable neuronal activation,
whereas stimulation at the soma required high voltages and produced delayed and
unreliable responses. Subthreshold stimulation at the soma depolarized the
somatic membrane potential without eliciting APs.
PMID- 27510731
TI - A community-based prospective cohort study of dengue viral infection in Malaysia:
the study protocol.
AB - BACKGROUND: Globally, dengue infections constitute a significant public health
burden. In recent decades, Malaysia has become a dengue hyper-endemic country
with the co-circulation of the four dengue virus serotypes. The cyclical
dominance of sub-types contributes to a pattern of major outbreaks. The
consequences can be observed in the rising incidence of reported dengue cases and
dengue related deaths. Understanding the complex interaction of the dengue virus,
its human hosts and the mosquito vectors at the community level may help develop
strategies for addressing the problem. METHODS: A prospective cohort study will
be conducted in Segamat district of Johor State in Peninsular Malaysia.
Researchers received approval from the Malaysian Medical Research Ethics
Committee and Monash University Human Research Ethics Committee. The study will
be conducted at a Malaysian based health and demographic surveillance site over a
1 year period in three different settings (urban, semi-urban and rural). The
study will recruit healthy adults (male and female) aged 18 years and over, from
three ethnic groups (Malay, Chinese and Indian). The sample size calculated using
the Fleiss method with continuity correction is 333. Sero-surveillance of
participants will be undertaken to identify asymptomatic, otherwise healthy
cases; cases with dengue fever who are managed as out-patients; and cases with
dengue fever admitted to a hospital. A genetic analysis of the participants will
be undertaken to determine whether there is a relationship between genetic
predisposition and disease severity. A detailed medical history, past history of
dengue infection, vaccination history against other flaviviruses such as Japanese
encephalitis and Yellow fever, and the family history of dengue infection will
also be collected. In addition, a mosquito surveillance will be carried out
simultaneously in recruitment areas to determine the molecular taxonomy of
circulating vectors. DISCUSSION: The research findings will estimate the burden
of asymptomatic and symptomatic dengue at the community level. It will also
examine the relationship between virus serotypes and host genotypes, and the
association of the clinical manifestation of the early phase with the entire
course of illness.
PMID- 27510734
TI - What Factors Do People with Joint Pain Feel are Important in Designing and
Developing Community Information-Based Self-Management Approaches? A Patient and
Public Engagement Report.
PMID- 27510735
TI - Spiny hyperkeratosis (trichodysplasia spinulosa-like eruption): a cutaneous
adverse effect of Hedgehog pathway inhibitors involving expression of p16.
PMID- 27510733
TI - A Panel of TrpB Biocatalysts Derived from Tryptophan Synthase through the
Transfer of Mutations that Mimic Allosteric Activation.
AB - Naturally occurring enzyme homologues often display highly divergent activity
with non-natural substrates. Exploiting this diversity with enzymes engineered
for new or altered function, however, is laborious because the engineering must
be replicated for each homologue. A small set of mutations of the tryptophan
synthase beta-subunit (TrpB) from Pyrococcus furiosus, which mimics the
activation afforded by binding of the alpha-subunit, was demonstrated to have a
similar activating effect in different TrpB homologues with as little as 57 %
sequence identity. Kinetic and spectroscopic analyses indicate that the mutations
function through the same mechanism: mimicry of alpha-subunit binding. From these
enzymes, we identified a new TrpB catalyst that displays a remarkably broad
activity profile in the synthesis of 5-substituted tryptophans. This demonstrates
that allosteric activation can be recapitulated throughout a protein family to
explore natural sequence diversity for desirable biocatalytic transformations.
PMID- 27510736
TI - Presenting changes in acoustic features synchronously to respiration alters the
affective evaluation of sound.
AB - Synchronization of respiration to cyclic auditory stimuli is a well-observed
phenomenon and known to have an effect on affective evaluation of the presented
sound. However, no studies have separated the effect of the change in respiratory
movement itself and that when there is synchrony between respiration and sound.
In this study, we used a system that can change the acoustic features
synchronously with the respiration phase and directly investigated the effect the
synchrony has on affective ratings without changing respiratory movements. An
acoustic stimulation was presented where the sound intensity (SI) or fundamental
frequency (F0) was modulated in response to the participant's respiration phase.
Affective evaluations of the acoustic stimuli were made by using the Self
Assessment Manikin (SAM). The experiments compared synchronous and asynchronous
conditions. In the synchronous condition, SI (or F0) was increased with
inhalation (decreased with exhalation) or decreased with inhalation (increased
with exhalation). In the asynchronous condition, a sound identical to that
presented in the synchronous condition was replayed. The participants evaluated
sounds that were acoustically the same but where the temporal relationship
differed between respiration and the acoustic features. In our results,
significantly higher arousal ratings were observed when the change in SI and
respiration (inhalation or exhalation) was synchronous and when the increase in
F0 and inhalation was synchronous. This suggests that the synchronous phenomenon
between respiration and auditory stimuli can play a critical role in affective
evaluation.
PMID- 27510737
TI - Development and validation of an ultra-performance convergence chromatography
method for the quality control of Angelica gigas Nakai.
AB - Ultra-performance convergence chromatography, which integrates the advantages of
supercritical fluid chromatography and ultra high performance liquid
chromatography technologies, is an environmentally friendly analytical method
that uses dramatically reduced amounts of organic solvents. An ultra-performance
convergence chromatography method was developed and validated for the
quantification of decursinol angelate and decursin in Angelica gigas using a CSH
Fluoro-Phenyl column (2.1 mm * 150 mm, 1.7 MUm) with a run time of 4 min. The
method had an improved resolution and a shorter analysis time in comparison to
the conventional high-performance liquid chromatography method. This method was
validated in terms of linearity, precision, and accuracy. The limits of detection
were 0.005 and 0.004 MUg/mL for decursinol angelate and decursin, respectively,
while the limits of quantitation were 0.014 and 0.012 MUg/mL, respectively. The
two components showed good regression (correlation coefficient (r2 ) > 0.999),
excellent precision (RSD < 2.28%), and acceptable recoveries (99.75-102.62%). The
proposed method can be used to efficiently separate, characterize, and quantify
decursinol angelate and decursin in Angelica gigas and its related medicinal
materials or preparations, with the advantages of a shorter analysis time,
greater sensitivity, and better environmental compatibility.
PMID- 27510739
TI - XL1st Sir Peter Freyer Memorial Lecture and Surgical Symposium Arts Millennium
Building, National University of Ireland Galway, 2nd & 3rd September 2016.
PMID- 27510738
TI - Reply to the article: Gleeson M et al. (2013) An audit of generic prescribing in
a general surgical department. Ir J Med Sci 182:403-408.
PMID- 27510740
TI - Physician Recommendations Trump Patient Preferences in Prostate Cancer Treatment
Decisions.
AB - OBJECTIVE: To assess the influence of patient preferences and urologist
recommendations in treatment decisions for clinically localized prostate cancer.
METHODS: We enrolled 257 men with clinically localized prostate cancer (prostate
specific antigen <20; Gleason score 6 or 7) seen by urologists (primarily
residents and fellows) in 4 Veterans Affairs medical centers. We measured
patients' baseline preferences prior to their urology appointments, including
initial treatment preference, cancer-related anxiety, and interest in sex. In
longitudinal follow-up, we determined which treatment patients received. We used
hierarchical logistic regression to determine the factors that predicted
treatment received (active treatment v. active surveillance) and urologist
recommendations. We also conducted a directed content analysis of recorded
clinical encounters to determine if urologists discussed patients' interest in
sex. RESULTS: Patients' initial treatment preferences did not predict receipt of
active treatment versus surveillance, Deltachi2(4) = 3.67, P = 0.45. Instead,
receipt of active treatment was predicted primarily by urologists'
recommendations, Deltachi2(2) = 32.81, P < 0.001. Urologists' recommendations, in
turn, were influenced heavily by medical factors (age and Gleason score) but were
unrelated to patient preferences, Deltachi2(6) = 0, P = 1. Urologists rarely
discussed patients' interest in sex (<15% of appointments). CONCLUSIONS:
Patients' treatment decisions were based largely on urologists' recommendations,
which, in turn, were based on medical factors (age and Gleason score) and not on
patients' personal views of the relative pros and cons of treatment alternatives.
PMID- 27510742
TI - Corrigendum to CSF-1 receptor signalling is governed by pre-requisite EHD1
mediated receptor display on the macrophage cell surface [Cell Signalling 2016
Sep.; 28(9): 1325-35].
PMID- 27510741
TI - A Randomized Trial of Expanding Choice Sets to Motivate Advance Directive
Completion.
AB - BACKGROUND: Evidence suggests that advance directives may improve end-of-life
care among seriously ill patients, but improving completion rates remains a
challenge. OBJECTIVE: This study tested the influence of increasing the number of
options for completing an advance directive among seriously ill patients.
METHODOLOGY: Outpatients ( N = 316) receiving hemodialysis across 15 dialysis
centers in the Philadelphia region between July 2014 and July 2015 were
randomized to receive either the option to complete a brief advance directive
form or expanded options including a brief, expanded, or comprehensive form.
Patients in both groups could decline to complete an advance directive or take
their selected version home. The primary outcome was a returned, completed
advance directive. Secondary outcomes included whether patients wanted to
complete an advance directive, decision satisfaction, quality of life at 3
months, and patient factors associated with advance directive completion.
RESULTS: Although offering more advance directive options was not significantly
associated with increased rates of completion (13.1% in the standard group v.
12.2% in the expanded group, P = 0.80), it did significantly increase the
proportion of patients who wanted to complete an advance directive and took one
home (71.9% in standard v. 85.3% in expanded, P = 0.004). There was no difference
in satisfaction ( P = 0.65) or change in quality of life between groups ( P =
0.63). A higher baseline quality of life was independently associated with
advance directive completion ( P = 0.006). CONCLUSIONS AND RELEVANCE: These
results suggest that although an expanded choice set may initially nudge patients
toward completing advance directives without restricting choice, increasing
actual completion requires additional interventions that overcome downstream
barriers.
PMID- 27510744
TI - A Stated Preference Approach to Assess whether Health Status Impacts on Marginal
Utility of Consumption.
AB - A sample of Danish citizens (n = 2000) was asked to participate in a hypothetical
experiment in which they could self-insure against a certain loss in income
across two periods of time (one in which the person is in good health and one in
which the person is in poorer health). Our results suggest that reduced health
impacts on the marginal utility of consumption, but not in a linear fashion.
Amongst a majority of respondents inferior, health increases the marginal utility
of consumption for intermediate health states, whereas this is not the case for
less and more severe health states. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27510743
TI - Joint level-set and spatio-temporal motion detection for cell segmentation.
AB - BACKGROUND: Cell segmentation is a critical step for quantification and
monitoring of cell cycle progression, cell migration, and growth control to
investigate cellular immune response, embryonic development, tumorigenesis, and
drug effects on live cells in time-lapse microscopy images. METHODS: In this
study, we propose a joint spatio-temporal diffusion and region-based level-set
optimization approach for moving cell segmentation. Moving regions are initially
detected in each set of three consecutive sequence images by numerically solving
a system of coupled spatio-temporal partial differential equations. In order to
standardize intensities of each frame, we apply a histogram transformation
approach to match the pixel intensities of each processed frame with an intensity
distribution model learned from all frames of the sequence during the training
stage. After the spatio-temporal diffusion stage is completed, we compute the
edge map by nonparametric density estimation using Parzen kernels. This process
is followed by watershed-based segmentation and moving cell detection. We use
this result as an initial level-set function to evolve the cell boundaries,
refine the delineation, and optimize the final segmentation result. RESULTS: We
applied this method to several datasets of fluorescence microscopy images with
varying levels of difficulty with respect to cell density, resolution, contrast,
and signal-to-noise ratio. We compared the results with those produced by Chan
and Vese segmentation, a temporally linked level-set technique, and nonlinear
diffusion-based segmentation. We validated all segmentation techniques against
reference masks provided by the international Cell Tracking Challenge consortium.
The proposed approach delineated cells with an average Dice similarity
coefficient of 89 % over a variety of simulated and real fluorescent image
sequences. It yielded average improvements of 11 % in segmentation accuracy
compared to both strictly spatial and temporally linked Chan-Vese techniques, and
4 % compared to the nonlinear spatio-temporal diffusion method. CONCLUSIONS:
Despite the wide variation in cell shape, density, mitotic events, and image
quality among the datasets, our proposed method produced promising segmentation
results. These results indicate the efficiency and robustness of this method
especially for mitotic events and low SNR imaging, enabling the application of
subsequent quantification tasks.
PMID- 27510746
TI - Synthesis of organic photosensitizers containing dithienogermole and
thiadiazolo[3,4-c]pyridine units for dye-sensitized solar cells.
AB - Dithienogermole (DTG) is a germanium-bridged bithiophene system that has been
applied as a building unit of conjugated materials for organic electronic
devices, including organic photovoltaics and organic light emitting diodes.
However, DTG has not been used as a component of sensitizers for dye-sensitized
solar cells (DSSCs). In this work, we have synthesized three D-pi-A-pi-A type
sensitizers containing DTG and thiadiazolo[3,4-c]pyridine (PTz). We expected that
combining DTG and a strong acceptor PTz would give rise to a strong absorption in
the visible region. In addition, we introduced bulky 2-ethylhexyl groups on the
germanium atom to prevent dye aggregation on TiO2 films. Three DTG-containing
dyes with different anchor units were synthesized and their
optical/electrochemical properties were investigated. The DTG-containing dyes
exhibited broad and strong absorption bands around 600 nm on TiO2. We fabricated
DSSCs based on the DTG-containing dyes. The onsets of incident photon to current
conversion efficiency (IPCE) spectra reached 900 nm and a maximal power
conversion efficiency of 2.76% was achieved.
PMID- 27510747
TI - Studying genetic resilience to improve human health.
PMID- 27510745
TI - N-acylhydrazone inhibitors of influenza virus PA endonuclease with versatile
metal binding modes.
AB - Influenza virus PA endonuclease has recently emerged as an attractive target for
the development of novel antiviral therapeutics. This is an enzyme with divalent
metal ion(s) (Mg(2+) or Mn(2+)) in its catalytic site: chelation of these metal
cofactors is an attractive strategy to inhibit enzymatic activity. Here we report
the activity of a series of N-acylhydrazones in an enzymatic assay with PA-Nter
endonuclease, as well as in cell-based influenza vRNP reconstitution and virus
yield assays. Several N-acylhydrazones were found to have promising anti
influenza activity in the low micromolar concentration range and good
selectivity. Computational docking studies are carried on to investigate the key
features that determine inhibition of the endonuclease enzyme by N
acylhydrazones. Moreover, we here describe the crystal structure of PA-Nter in
complex with one of the most active inhibitors, revealing its interactions within
the protein's active site.
PMID- 27510748
TI - Overexpression of transport proteins improves the production of 5-aminovalerate
from l-lysine in Escherichia coli.
AB - Bacterial transporters mediate the exchanges between intracellular and
extracellular environments. Modification of transport route could be applied to
speed up the metabolic reactions and promote the production of aimed compounds.
Herein, lysine 2-monooxygenase (DavB) and delta-aminovaleramidase (DavA) were co
expressed in Escherichia coli BL21(DE3) to produce nylon-5 monomer 5
aminovalerate from l-lysine. Then, PP2911 (4-aminobutyrate transporter in
Pseudomonas putida) and LysP (the lysine specific permease in E. coli) were
overexpressed to promote 5-aminovalerate production using whole cells of
recombinant E. coli. The constructed E. coli strain overexpressing transport
proteins exhibited good 5-aminovalerate production performance and might serve as
a promising biocatalyst for 5-aminovalerate production from l-lysine. This
strategy not only shows an efficient process for the production of nylon monomers
but also might be used in production of other chemicals.
PMID- 27510749
TI - Anhydrobiosis in yeast: cell wall mannoproteins are important for yeast
Saccharomyces cerevisiae resistance to dehydration.
AB - The state of anhydrobiosis is linked with the reversible delay of metabolism as a
result of strong dehydration of cells, and is widely distributed in nature. A
number of factors responsible for the maintenance of organisms' viability in
these conditions have been revealed. This study was directed to understanding how
changes in cell wall structure may influence the resistance of yeasts to
dehydration-rehydration. Mutants lacking various cell wall mannoproteins were
tested to address this issue. It was revealed that mutants lacking proteins
belonging to two structurally and functionally unrelated groups (proteins non
covalently attached to the cell wall, and Pir proteins) possessed significantly
lower cell resistance to dehydration-rehydration than the mother wild-type
strain. At the same time, the absence of the GPI-anchored cell wall protein Ccw12
unexpectedly resulted in an increase of cell resistance to this treatment; this
phenomenon is explained by the compensatory synthesis of chitin. The results
clearly indicate that the cell wall structure/composition relates to parameters
strongly influencing yeast viability during the processes of dehydration
rehydration, and that damage to cell wall proteins during yeast desiccation can
be an important factor leading to cell death. Copyright (c) 2016 John Wiley &
Sons, Ltd.
PMID- 27510750
TI - Sonic hedgehog protein regulates fibroblast growth factor 8 expression in
metanephric explant culture from BALB/c mice: Possible mechanisms associated with
renal morphogenesis.
AB - The sonic hedgehog (SHH) morphogen regulates cell differentiation and controls a
number of genes during renal morphogenesis. To date, the effects of SHH on
fibroblast growth factors (Fgfs) in embryonic kidney development remain unclear.
In the present study, explants of BALB/c mouse embryonic kidney tissues were used
to investigate the role of exogenous SHH on Fgf8 and Fgf10 expression levels ex
vivo. Ureteric bud branches and epithelial metanephric derivatives were used to
determine the renal morphogenesis with Dolichos biflorus agglutinin or
hematoxylin-eosin staining. mRNA expression levels were determined using reverse
transcription-quantitative polymerase chain reaction, while the protein
expression levels were examined using immunohistochemistry and western blot
analysis. During the initial stages of metanephric development, low levels of
SHH, Fgf8, and Fgf10 expression were observed, which were found to increase
significantly during more advanced stages of metanephric development. In
addition, exogenous SHH protein treatment increased the number of ureteric bud
branches and enhanced the formation of nephrons. Exogenous SHH reduced the Fgf8
mRNA and protein expression levels, whereas cyclopamine (an SHH-smoothened
receptor inhibitor) interfered with SHH-mediated downregulation of Fgf8
expression. By contrast, exogenous SHH protein was not found to modulate Fgf10
mRNA and protein expression levels. In conclusion, these results indicate that
the modulatory effects of SHH on BALB/c mouse metanephric explant cultures may
involve the regulation of Fgf8 expression but not Fgf10 expression, which
provides evidence for the functional role of Fgf proteins in renal morphogenesis.
PMID- 27510751
TI - Prevalence and Predictors of Gastroesophageal Reflux Complications in Community
Subjects.
AB - BACKGROUND: Predictors of erosive esophagitis (EE) and Barrett's esophagus (BE)
and the influence of number of risk factors in the community are not well
defined. METHODS: Rates of BE and EE among community residents identified in a
randomized screening trial were defined. The risk of EE and BE associated with
single and multiple risk factors (gender, age, GERD, Caucasian ethnicity, ever
tobacco use, excess alcohol use, family history of BE or EAC, and central
obesity) was analyzed. RESULTS: Sixty-eight (33 %) of 205 subjects had EE and/or
BE. BE prevalence was 7.8 % with dysplasia present in 1.5 %. Rates were
comparable between subjects with and without GERD. Male sex and central obesity
were independent risk factors. The odds of EE or BE were 3.7 times higher in
subjects with three or four risk factors and 5.7 times higher in subjects with
five or more risk factors compared with those with two or less factors.
CONCLUSIONS: EE and BE are prevalent in the community regardless of the presence
of GERD. Risk appeared to be additive, increasing substantially with three or
more risk factors.
PMID- 27510752
TI - Frequency of and Factors Associated with Receipt of Liver-Related Specialty Care
Among Patients with Hepatitis C in the Chronic Hepatitis Cohort Study.
AB - BACKGROUND: Linking persons with hepatitis C virus (HCV) to care and treatment is
critical to reduction in disease burden; typically, this entailed referral to a
specialist. However, data regarding the frequency and factors associated with
referral among patients in healthcare organizations (HCOs) are lacking. METHODS:
Among persons in four US HCOs with newly diagnosed HCV during 2006-2011, we
determined the frequency of liver-related specialist care after diagnosis. We
also identified sociodemographic and clinical characteristics associated with
such care by multivariate analysis, adjusted for all variables. RESULTS: Among
3592 patients with newly diagnosed HCV, 57 % (range among sites 45-90 %) received
specialist care; of these, 57 % received care within 90 days of diagnosis.
Patient characteristics associated with receipt of specialist care included:
affiliation with one of the study sites [adjusted odds ratio (aOR) 4.8 vs. the
referent site); having Medicare plus private insurance (aOR 1.6 vs. Medicaid);
and having elevated alanine aminotransferase (ALT) (aOR 1.6 vs. normal ALT) or
lower platelet values (aOR 1.4 vs. normal platelet level). Specialist care within
90 days of diagnosis was associated with private insurance (aOR 1.5 vs.
Medicaid), elevated ALT levels (aOR 1.3-2.3 vs. normal), and having >=2 comorbid
conditions (aOR 1.4 vs. no comorbid conditions). Compared to patients not
referred, those referred were more likely to be treated (aOR 3.5). CONCLUSIONS:
Receipt of specialist care among persons with newly diagnosed HCV varied among
HCOs. Clinical evidence of liver disease and having private insurance were
associated with prompt receipt of specialist care and HCV treatment.
PMID- 27510753
TI - Gastrointestinal Bleeding During the Index Hospitalization for Mechanical
Circulatory Support Devices Implantation, a Nationwide Perspective.
AB - BACKGROUND: Gastrointestinal bleeding (GIB) is a common adverse event after
mechanical circulatory support device implantation. However, the majority of the
reported data were obtained from small single-center studies. Our aim was to
study the prevalence and predictors of GIB during the index hospitalization of
mechanical circulatory support devices implantation using a nationwide database.
METHODS: Nationwide inpatient sample (2009-2011) was used to perform a
retrospective cross-sectional study. Adult patients with discharge diagnosis
codes of congestive heart failure and procedure codes of left-ventricular assist
device (LVAD) or intra-aortic balloon pump (IABP) implantation or orthotopic
heart transplant (OHT, reference group) were identified. Our outcome was GIB
during the index hospitalization when the device was implanted. Predictors that
achieved statistical significance on the univariate analysis were included in a
multivariable logistic-regression analysis. RESULTS: A total of 87,462 patients
were included, 87 % of the patients received an IABP, 6 % received LVAD, and 5 %
underwent OHT. Prevalence of GIB was 8, 5, and 3 % among those who had LVAD, IABP
implantation, and OHT recipients, respectively (p < 0.001). Patients who
underwent LVAD implantation had twofold increase in the prevalence of GIB (OR
2.1, 1.7-2.5, p < 0.001) when using IABP or OHT groups as a reference. This
increase in the prevalence was not demonstrated among IABP recipients on a
multivariate level. CONCLUSION: Prevalence of GIB was higher among LVAD compared
to OHT and IABP recipients and could occur as early as the index admission of the
device implantation.
PMID- 27510754
TI - Correction: A pH-driven, reconfigurable DNA nanotriangle.
AB - Correction for 'A pH-driven, reconfigurable DNA nanotriangle' by Wenxing Wang et
al., Chem. Commun., 2009, 824-826.
PMID- 27510755
TI - Toward Reducing Ageism: PEACE (Positive Education about Aging and Contact
Experiences) Model.
AB - The population of older adults is growing worldwide. Negative ageism (negative
attitudes and behavior toward older adults) is a serious international concern
that negatively influences not only older adults but also individuals across the
age continuum. This article proposes and examines the application of an
integrative theoretical model across empirical evidence in the literature on
ageism in psychology, medicine, social work, and sociology. The proposed Positive
Education about Aging and Contact Experiences (PEACE) model focuses on 2 key
contributing factors expected to reduce negative ageism: (a) education about
aging including facts on aging along with positive older role models that dispel
negative and inaccurate images of older adulthood; and (b) positive contact
experiences with older adults that are individualized, provide or promote equal
status, are cooperative, involve sharing of personal information, and are
sanctioned within the setting. These 2 key contributing factors have the
potential to be interconnected and work together to reduce negative stereotypes,
aging anxiety, prejudice, and discrimination associated with older adults and
aging. This model has implications for policies and programs that can improve the
health and well-being of individuals, as well as expand the residential,
educational, and career options of individuals across the age continuum.
PMID- 27510756
TI - The protective role of p72 in doxorubicin-induced cardiomyocytes injury in vitro.
AB - p72 (probable ATP-dependent RNA helicase DDX17) belongs to the DEAD-box RNA
helicase family. p72 is important in RNA processing. Thus, the role of p72 in
doxorubicin (DOX)-induced cardiomyocyte injury was investigated in the present
study. The changes in p72 expression levels were studied in cultured neonatal
cardiomyocytes and p72 overexpression was induced using adenovirus vectors. To
investigate the production of reactive oxygen species (ROS), dihydroethidium
staining was conducted. TUNEL and Hoechst staining were used to indicate cell
apoptosis. Microarrays were used to determine the altered expression of
microRNAs. In DOX-induced cardiomyocyte injury, the protein expression level of
p72 was reduced. Overexpression of p72 protected cardiomyocytes from DOX-induced
ROS production and cell apoptosis. p72 reduced the activation of estrogen
receptor alpha (ERalpha), thereby reducing DOX-induced cell apoptosis. The
present study indicated that p72 exerts a protective effect against DOX-induced
cell apoptosis via inhibition of ERalpha activation, indicating this may be a
potential target of therapy for cardiac injury.
PMID- 27510757
TI - Protective Effect of Metformin against Acute Inflammation and Oxidative Stress in
Rat.
AB - Preclinical Research The antidiabetic drug, metformin, can inhibit the release of
inflammatory mediators in several disease conditions. The present study was
carried out to evaluate the efficacy of metformin in ameliorating edema
formation, oxidative stress, mediator release and vascular changes associated
with acute inflammation in the rat carrageenan model. Metformin dose-dependently
inhibited paw swelling induced by carrageenan and normalized the tissue levels of
the inflammatory markers myeloperoxidase and nitrite. It also maintained
oxidative homeostasis as indicated by near normal levels of the oxidative stress
markers glutathione, thiobarbituric acid reactive substances, catalase and
superoxide dismutase. The histopathology of the paw tissue in metformin-treated
animals was similar to that in normal paw and had similar effects to diclofenac.
In a rat peritonitis model, metformin reduced vascular permeability and cellular
infiltration. In conclusion, this study shows that metformin has a potential for
use in treating various inflammatory conditions.
PMID- 27510758
TI - Niacin for phosphate control: A case of David versus Goliath.
PMID- 27510759
TI - Tinea capitis: a retrospective epidemiological comparative study.
AB - BACKGROUND: Currently, a wide spectrum of retrospective studies regarding the
incidence of TC among children and adults are available in the world literature,
but none of them are comparative, aiming to distinguish etiological diversity
depending on the different geographic areas. OBJECTIVE: This study aimed to
investigate the epidemiology of TC in Plovdiv, Bulgaria and Thessaloniki, and
Greece, and to compare the results and predominant etiological agents using
retrospective comparative analysis for an 11-year time period. MATERIALS AND
METHODS: The subjects included were selected from archives of the Mycological
Laboratory of the University Dermatologic Clinic, University Hospital "St.
George" Plovdiv, Bulgaria, and the Mycological Laboratory of the First
Dermatology Department of Aristotle University Thessaloniki, Greece, by
retrospective analysis of data from an 11-year time period (2004-2014). A total
count of 374 children aged 0-18, with confirmed diagnosis of TC via direct
mycological examination and culture were included (128 children from Plovdiv,
Bulgaria, and 246 children from Thessaloniki, Greece). Samples were plated on
Sabouraud agar, followed by species identification of the isolated colonies.
RESULTS: Our results demonstrate that the incidence of TC in the region of
Bulgaria and Thessaloniki for the investigated period was lower than for the
previously reported period. In Plovdiv, Bulgaria, it was 1.20 +/- 0.09 % (n = 172
from a total count of 14,278 cases of mycoses), as the disease accounts for 23.10
+/- 1.79 % of all mycological infections among the pediatric population and 0.36
+/- 0.05 % (n = 49 from a total count of 13,724) among the adults patients in
Plovdiv, Bulgaria. The incidence of the disease during the period 2004-2014 in
Thessaloniki was 2.49 +/- 0.15 % (n = 253 cases of TC from a total count of
10,168 mycoses), as it accounts for approximately 27.06 +/- 1.47 % of mycological
infections among the pediatric population in Thessaloniki, Greece, and 0.08 +/-
0.03 % (n = 7 from a total count of 9259) of the population of adult patients
with mycoses. Our study confirmed the presumption that M. canis is the leader
among the causative agents in TC in children in both of the included countries,
but its presence in the etiology of disease in adult patients was very low and
nonsignificant. We categorically identified dominance of the female gender among
the children with TC in Plovdiv, Bulgaria; while in Thessaloniki, Greece, the
gender distribution had an almost equal ratio of males to females. CONCLUSION:
Our results suggest that the gender predisposition depends also on the
investigated geographic region and the time of the study, rather than only on the
causative pathogen and age.
PMID- 27510760
TI - Localized Down-regulation of P-glycoprotein by Focused Ultrasound and
Microbubbles induced Blood-Brain Barrier Disruption in Rat Brain.
AB - Multi-drug resistant efflux transporters found in Blood-Brain Barrier (BBB) acts
as a functional barrier, by pumping out most of the drugs into the blood.
Previous studies showed focused ultrasound (FUS) induced microbubble oscillation
can disrupt the BBB by loosening the tight junctions in the brain endothelial
cells; however, no study was performed to investigate its impact on the
functional barrier of the BBB. In this study, the BBB in rat brains were
disrupted using the MRI guided FUS and microbubbles. The immunofluorescence study
evaluated the expression of the P-glycoprotein (P-gp), the most dominant multi
drug resistant protein found in the BBB. Intensity of the P-gp expression at the
BBB disruption (BBBD) regions was significantly reduced (63.2 +/- 18.4%) compared
to the control area. The magnitude of the BBBD and the level of the P-gp down
regulation were significantly correlated. Both the immunofluorescence and
histologic analysis at the BBBD regions revealed no apparent damage in the brain
endothelial cells. The results demonstrate that the FUS and microbubbles can
induce a localized down-regulation of P-gp expression in rat brain. The study
suggests a clinically translation of this method to treat neural diseases through
targeted delivery of the wide ranges of brain disorder related drugs.
PMID- 27510761
TI - Challenging the wisdom of puncture at the calyceal fornix in percutaneous
nephrolithotripsy: feasibility and safety study with 137 patients operated via a
non-calyceal percutaneous track.
AB - OBJECTIVES: To present our experience with a central, non-calyceal puncture
protocol for percutaneous nephrolithotripsy (PCNL) in an attempt to challenge the
opinion of worldwide adopted calyceal puncture as the less traumatic site of
percutaneous entrance into the collecting system. PATIENTS AND METHODS: During
2012, a total of 137 consecutive, unselected patients were subjected to PCNL in
our department. Non-calyceal punctures were performed to all cases and followed
by subsequent track dilations up to 30 Fr. Perioperative and postoperative data
were prospectively collected and analyzed. RESULTS: Mean operative time (from
skin puncture to nephrostomy tube placement) was 48 min. Patients with single,
multiple and staghorn stones had primary stone-free rates of 89.2, 80.4 and 66.7
% after PCNL, respectively. The overall complication rate was 10.2 %, while
bleeding complications were minimal. Only 4 patients (2.9 %) required blood
transfusion. Five patients (3.6 %) had Clavien Grade IIIa complications requiring
an intervention for their management and none Grade IV or V. CONCLUSIONS: Despite
the absence of evidence that non-calyceal percutaneous tracts could be a risk
factor for complications, the concept of calyceal puncture has been worldwide
adopted by PCNL surgeons as the sole safe percutaneous entrance into the
collective system. Based on our experience, other pathways than the worldwide
recognized rule, calyceal puncture, are possible and probably not as dangerous as
has been previously stated.
PMID- 27510762
TI - Performance of PI-RADS version 1 versus version 2 regarding the relation with
histopathological results.
AB - PURPOSE: Aim of this study was to compare the diagnostic performance of PI-RADS
version 1 (v1) and version 2 (v2) in the detection of prostate cancer (PCa).
METHODS: Multiparametric MRIs (mpMRI) of 50 consecutive patients with biopsy
proven PCa, which had originally been evaluated according to PIRADS v1, were now
retrospectively re-evaluated, comparing PI-RADS v1 and v2. MpMRI data were
evaluated in comparison with histopathological whole-mount step-section slides.
MRI examinations included T2-weighted, diffusion-weighted, and dynamic contrast
enhanced MRI. RESULTS: Overall PI-RADS v1 showed a significantly larger
discriminative ability of tumor detection: PI-RADS v1 AUC 0.96 (95 % CI 0.94
0.98) and v2 AUC 0.90 (95 % CI 0.86-0.94). For peripheral zone lesions, PI-RADS
v1 showed a significantly larger ability of PCa discrimination: v1 AUC 0.97 (95 %
CI 0.95-0.99) and v2 AUC 0.92 (95 % CI 0.88-0.96). For transition zone lesions,
PI-RADS v1 showed more discrimination: v1 AUC 0.96 (95 % CI 0.92-1.00) and v2
0.90 (95 % CI 0.83-0.97), but the difference was not significant. PI-RADS v2
resulted in significantly more false negative results (3 % in v1, 14 % in v2) and
a comparable number of true positive results (82 % in v1, 80 % in v2).
CONCLUSION: PI-RADS v2 uses a simplified approach, but shows a lower diagnostic
accuracy. This could lead to a higher rate of false negative results with the
risk of missing tumors within low PI-RADS score levels. Therefore, its use cannot
be recommended unconditionally, and further improvement should be considered.
PMID- 27510763
TI - Laterally Confined Microfluidic Patterning of Cells for Engineering Spatially
Defined Vascularization.
AB - A biofabrication strategy for creating planar multiscale protein, hydrogel, and
cellular patterns, and simultaneously generating microscale topographical
features is developed that laterally confines the patterned cells and direct
their growth in cell permissive hydrogels.
PMID- 27510764
TI - Vitamin E is the major contributor to the antioxidant capacity in lambs fed whole
dried citrus pulp.
AB - The aim of this study was to investigate the effect of dietary whole dried citrus
pulp (DCP) on the antioxidant status of lamb tissues. In total, 17 lambs were
divided into two groups and fed for 56 days: a barley-based concentrate diet (CON
- eight animals), or a concentrate-based diet including 35% DCP to partially
replace barley (CIT - nine animals). The CIT diet contained a double
concentration of phenolic compounds than the CON diet (7.9 v. 4.0 g/kg dry matter
(DM), respectively), but had no effect (P>0.05) on the overall antioxidant
capacity of the hydrophilic fraction of blood plasma, liver and muscle. The CIT
diet contained clearly more alpha-tocopherol than the CON diet (45.7 v. 10.3
mg/kg DM), which could explain the higher concentration of alpha-tocopherol in
liver, plasma and muscle (P<0.05). The dietary treatment had no effect on the
extent of lipid peroxidation, measured as thiobarbituric acid and reactive
substances assay (TBARS values) in the faeces, small intestine, liver, plasma and
muscle. Nevertheless, when muscle homogenates were incubated in the presence of
Fe3+/ascorbate to induce lipid peroxidation, the muscle from lambs fed DCP
displayed lower TBARS values (P<0.01), which negatively correlated with the
concentration of alpha-tocopherol in muscle. These results showed that feeding
whole DCP to ruminants increases the antioxidant status of muscle through an
increase in the deposition of alpha-tocopherol.
PMID- 27510765
TI - Number of accelerometer monitoring days needed for stable group-level estimates
of activity.
AB - To determine the number and distribution of days required to produce stable group
level estimates of a 7 d mean for common accelerometer-derived activity measures.
Data from the 2003-2006 NHANES were used in this analysis. The sample included
986 youth (6-19 year) and 2532 adults (?20 year) with 7 d of ?10 h of wear.
Accelerometer measures included minutes of inactive, light physical activity,
moderate-to-vigorous physical activity (MVPA); and total activity counts/d.
Twenty-five alternative protocols were bootstrapped with 50 000 samples drawn for
each protocol. Alternative protocols included: 1-6 random days, Saturday plus 1-5
random weekdays (WD), Sunday plus 1-5 random WD, 1 random weekend day (WE) plus 1
5 WD, and both WE plus 1-4 random WD. Relative difference was calculated between
the 7 d mean and alternative protocol mean (((alternative protocol mean - 7 d
mean)/7 d mean) (*) 100). Adult MVPA is used as an example; however, similar
trends were observed across age groups and variables except adult inactive time,
which was stable across protocols. The 7 d mean for adult MVPA was 44.1(0.9) min
d(-1). The mean bias for any 1-6 random days ranged from -0.0(0.3) to 0.0(0.2)
min d(-1) with a relative difference of -0.1 to 0.0%. For protocols with non
random components, bias ranged from -1.4(0.2) to 0.6(0.1) min d(-1) with
relative difference ranging from -7.2 to 3.1%. Simulation data suggest that
stable estimates of group-level means can be obtained from as few as one randomly
selected monitoring day from a sampled week. On the other hand, estimates using
non-random selection of weekend days may be significantly biased. Purposeful
sampling that disproportionally forces inclusion of weekend data in analyses
should be discouraged.
PMID- 27510766
TI - Proteomic analysis of an engineered isolate of Lactobacillus plantarum with
enhanced raffinose metabolic capacity.
AB - Lactic acid bacteria that can produce alpha-galactosidase are a promising
solution for improving the nutritional value of soy-derived products. For their
commercial use in the manufacturing process, it is essential to understand the
catabolic mechanisms that facilitate their growth and performance. In this study,
we used comparative proteomic analysis to compare catabolism in an engineered
isolate of Lactobacillus plantarum P-8 with enhanced raffinose metabolic
capacity, with the parent (or wild-type) isolate from which it was derived. When
growing on semi-defined medium with raffinose, a total of one hundred and twenty
five proteins were significantly up-regulated (>1.5 fold, P < 0.05) in the
engineered isolate, whilst and one hundred and six proteins were significantly
down-regulated (<-1.5 fold, P < 0.05). During the late stages of growth, the
engineered isolate was able to utilise alternative carbohydrates such as sorbitol
instead of raffinose to sustain cell division. To avoid acid damage the cell
layer of the engineered isolate altered through a combination of de novo fatty
acid biosynthesis and modification of existing lipid membrane phospholipid acyl
chains. Interestingly, aspartate and glutamate metabolism was associated with
this acid response. Higher intracellular aspartate and glutamate levels in the
engineered isolate compared with the parent isolate were confirmed by further
chemical analysis. Our study will underpin the future use of this engineered
isolate in the manufacture of soymilk products.
PMID- 27510767
TI - True ferroelectric switching in thin films of trialkylbenzene-1,3,5
tricarboxamide (BTA).
AB - We have investigated the ferroelectric polarization switching properties of
trialkylbenzene-1,3,5-tricarboxamide (BTA), which is a model system for a large
class of novel organic ferroelectric materials. In the solid state BTAs form a
liquid crystalline columnar hexagonal phase that provides long range order that
was previously shown to give rise to hysteretic dipolar switching. In this work
the nature of the polar switching process is investigated by a combination of
dielectric relaxation spectroscopy, depth-resolved pyroelectric response
measurements, and classical frequency- and time-dependent electrical switching.
We show that BTAs, when brought in a homeotropically aligned hexagonal liquid
crystalline phase, are truly ferroelectric. Analysis of the transient switching
behavior suggests that the ferroelectric switching is limited by a highly
dispersive nucleation process, giving rise to a wide distribution of switching
times.
PMID- 27510768
TI - Real-time PCR detection and phylogenetic relationships of Neorickettsia spp. in
digeneans from Egypt, Philippines, Thailand, Vietnam and the United States.
AB - Neorickettsia (Rickettsiales, Anaplasmataceae) is a genus of obligate
intracellular bacterial endosymbionts of digeneans (Platyhelminthes, Digenea).
Some Neorickettsia are able to invade cells of the digenean's vertebrate host and
are known to cause diseases of domestic animals, wildlife, and humans. In this
study we report the results of screening digenean samples for Neorickettsia
collected from bats in Egypt and Mindoro Island, Philippines, snails and fishes
from Thailand, and fishes from Vietnam and the USA. Neorickettsia were detected
using a real-time PCR protocol targeting a 152bp fragment of the heat shock
protein coding gene, GroEL, and verified with nested PCR and sequencing of a
1853bp long region of the GroESL operon and a 1371bp long region of 16S rRNA.
Eight unique genotypes of Neorickettsia were obtained from digenean samples.
Neorickettsia sp. 8 obtained from Lecithodendrium sp. from Egypt; Neorickettsia
sp. 9 and 10 obtained from two species of Paralecithodendrium from Mindoro,
Philippines; Neorickettsia sp. 11 from Lecithodendrium sp. and Neorickettsia sp.
4 (previously identified from Saccocoelioides lizae, from China) from Thailand;
Neorickettsia sp. 12 from Dicrogaster sp. Florida, USA; Neorickettsia sp. 13 and
SF agent from Vietnam. Sequence comparison and phylogenetic analysis demonstrated
that the forms, provisionally named Neorickettsia sp. 8-13, represent new
genotypes. We have for the first time detected Neorickettsia in a digenean from
Egypt (and the African continent as a whole), the Philippines, Thailand and
Vietnam based on PCR and sequencing evidence. Our findings suggest that further
surveys from the African continent, SE Asia, and island countries are likely to
reveal new Neorickettsia lineages as well as new digenean host associations.
PMID- 27510770
TI - Erratum to: eSTGt: a programming and simulation environment for population
dynamics.
PMID- 27510771
TI - [The standardized development of breast pathology in recent years of China].
PMID- 27510772
TI - [Granulomatous lobular mastitis: clinical pathological diagnosis and differential
diagnosis].
PMID- 27510769
TI - cPKCgamma-Modulated Autophagy in Neurons Alleviates Ischemic Injury in Brain of
Mice with Ischemic Stroke Through Akt-mTOR Pathway.
AB - We have reported that neuron-specific conventional protein kinase C (cPKC)gamma
is involved in the development of cerebral hypoxic preconditioning (HPC) and the
neuroprotection against ischemic injuries, but its molecular mechanism is
unclear. In this study, the adult and postnatal 24 h C57BL/6J wild-type
(cPKCgamma+/+) and cPKCgamma knockout (cPKCgamma-/-) mice were respectively used
to establish the models of middle cerebral artery occlusion (MCAO)-induced
ischemic stroke in vivo and oxygen-glucose deprivation (OGD)-treated primarily
cultured cortical neurons as cell ischemia in vitro. The results showed that
cPKCgamma knockout could increase the infarct volume and neuronal cell loss in
the peri-infarct region, and enhance the neurological deficits, the impaired
coordination, and the reduced muscle strength of mice following 1 h MCAO/1-7 days
reperfusion. Meanwhile, cPKCgamma knockout significantly increased the conversion
of LC3-I to LC3-II and beclin-1 protein expression, and resulted in more
reductions in P-Akt, P-mTOR, and P-S6 phosphorylation levels in the peri-infarct
region of mice with ischemic stroke. The autophagy inhibitor BafA1 could enhance
or reduce neuronal cell loss in the peri-infarct region of cPKCgamma+/+ and
cPKCgamma-/- mice after ischemic stroke. In addition, cPKCgamma knockout and
restoration could aggravate or alleviate OGD-induced neuronal ischemic injury in
vitro through Akt-mTOR pathway-mediated autophagy. These results suggested that
cPKCgamma-modulated neuron-specific autophagy improves the neurological outcome
of mice following ischemic stroke through the Akt-mTOR pathway, providing a
potential therapeutic target for ischemic stroke.
PMID- 27510773
TI - [2016 World Health Organization classification of tumors of the prostate: an
update].
PMID- 27510774
TI - [2016 World Health Organization classification of tumors of the testis and the
penis: an update].
PMID- 27510775
TI - [Standardization for diagnostic tumor pathology].
PMID- 27510776
TI - [Standardization for diagnostic tumor pathology (breast cancer)].
PMID- 27510777
TI - [Guidelines for HER2 detection in gastric cancer(2016)].
PMID- 27510778
TI - [Association of single nucleotide polymorphisms in PAI-1 with breast cancer
susceptibility and prognosis].
AB - OBJECTIVE: To study the effects of single nucleotide polymorphisms (SNP) in
Plasminogen activator inhibitor 1(PAI-1) on breast cancer susceptibility and
patients' prognosis among a Chinese Han women population. METHODS: Six tag SNP
(tSNP) of PAI-1 were selected according to HapMap CHB population, and TaqMan
realtime PCR method was used to genotype the 6 tSNP in 1 160 breast cancer cases
and 1 318 age-matched controls among Chinese Han women. Haplotypes and diplotypes
were inferred according to genotyping data and linkage disequilibrium. Finally,
the associations of tSNP, haplotypes and dipltypes with breast cancer
susceptibility and patients' prognosis were analyzed. RESULTS: Regarding to
breast cancer susceptibility, for rs6090 (G>A), AA genotype carriers had 3.79
times higher risk of developing breast cancer (OR=4.79, 95%CI=1.01-22.64, P=0.048
0) than GG or GA genotype carriers. For rs2227672 (G>T), TT genotype carriers had
1.52 times higher breast cancer risk than GG or GT genotype carriers (OR=2.52,
95%CI=1.26-5.01, P=0.008 6). Regarding to breast cancer prognosis, women who
carried rs2227692 (C>T) CT genotype had 46% lower risk of developing recurrence,
metastasis or death than CC genotype carriers (HR=0.54, 95%CI=0.30-0.97, P=0.040
4). Using stratified association analysis, among BMI<23 patients, those women who
carried AA genotype of rs2227631 (G>A) had 3.99 times higher risk of developing
the events (recurrence, metastasis or death) than GG or GA genotype carriers
(HR=4.99, 95%CI=1.66-15.02, P=0.004 2). Among HER2 positive patients, those women
who carried AA genotype of rs2227667 (G>A) had 2.98 times higher risk of
developing the events (recurrence, metastasis or death) than GG or GA genotype
carriers (HR=3.98, 95%CI=1.47-10.80, P=0.006 7). Among patients with tumors>2 cm,
those women who carried rs2227692 (C>T) CT or TT genotype had 51% lower risk of
developing the events (recurrence, metastasis or death) than CC genotype carriers
(HR=0.49, 95%CI=0.27-0.88, P=0.017 0). CONCLUSIONS: The study indicates that
single nucleotide polymorphisms in PAI-1 may affect breast cancer susceptibility
and survival in Chinese Han women. The study may contribute to individualized
evaluation of breast cancer risk and patients' prognosis if these data are
validated in some other Chinese Han populations.
PMID- 27510779
TI - [CD8 and FOXP3 expression in stromal tumor-infiltrating lymphocytes of triple
negative breast carcinomas: a clinicopathologic study].
AB - OBJECTIVE: To investigate the relationship between stromal tumor-infiltrating
lymphocytes (TIL) and CD8 or FOXP3 positive lymphocytes in triple-negative breast
carcinoma. METHODS: A total of 160 triple-negative breast carcinomas were
collected from the First Affiliated Hospital of Nanjing Medical University during
2012 to 2014. All were surgical excision or biopsy specimens from patients
without prior chemotherapy and radiotherapy. Histopathologic analysis of stromal
TIL was performed on hematoxylin and eosin-stained sections, and MaxVision
immunohistochemical method was used for detection of CD8 and FOXP3 protein
expression. RESULTS: Stromal TILs were positively correlated with Ki-67 labeling
index (P=0.002). The density of CD8(+) cytotoxic T-lymphocyte (CTL) was
negatively correlated with tumor size (P=0.009), and positively correlated with
Ki-67 index (P=0.021). The density of FOXP3(+) regulatory T-lymphocyte (Treg) was
inversely correlated with the patient age (P=0.030), and positively correlated
with histological grade (P=0.026). Stromal TILs were positively correlated with
the density of CD8(+) CTL (P=0.014). CONCLUSIONS: The percentage of stromal TILs
and density of CD8(+) CTL are associated with tumor cell proliferation of triple
negative breast cancers. The density of FOXP3(+) Treg is significantly associated
with poor prognosis. Stromal TIL is positively correlated with the density of
CD8(+) CTL. Stromal TIL may provide a potential marker for pathological diagnosis
and a target for guiding adjuvant therapy in patients with triple-negative breast
cancers.
PMID- 27510780
TI - [Impact of 2013 American Society of Clinical Oncology/College of American
Pathologist guidelines on borderline immunostaining results for HER2: a
retrospective study on HER2 FISH results in 1 780 cases of invasive breast
cancers].
AB - OBJECTIVE: To analyze the impact of the revised 2013 American Society of Clinical
Oncology/College of American Pathologist(ASCO/CAP)HER2 testing guidelines on the
status of HER2 and its clinical significance in invasive breast cancers by
fluorescent in situ hybridization(FISH). METHODS: One thousand seven hundred and
eighty invasive breast cancer cases with equivocal 2+ immunostaining detected by
FISH were retrospectively selected from 2010 to 2014, and the HER2/CEP17 dual
probe results were evaluated according to both the 2007 and 2013 ASCO/CAP
guidelines for comparative analysis. RESULTS: Among the 1 780 IHC HER2 (2+ )
invasive breast cancers, the number of HER2 positive, equivocal and negative case
were 310(17.41%), 66(3.71%)and 1 404(78.88%) respectively, basing on the 2007
guidelines; whereas basing on the 2013 ASCO/CAP HER2 guidelines, the number of
HER2 positive, equivocal and negative case was 360 (20.22%), 182 (10.23%)and 1
238 (69.55%) respectively. Compared with the 2007 guidelines, the proportion of
positive and equivocal cases were higher in the 2013 guidelines (17.41% versus
20.22%, 3.71% versus 10.23% respectively), while the proportion of negative cases
was lower(78.88% versus 69.55%). CONCLUSIONS: Using the 2013 ASCO/CAP guidelines
could lead to an increase in positive and equivocal cases, and a decrease in
negative cases. The increase can probably be attributable to the inclusion of
HER2 copy number besides HER2/CEP17 ratio as positive criteria, and it improves
the accuracy and may be of important value for screening more population who
benefit from HER2 targeting treatment; however the benefits for HER2 positive
with low HER2 copy number and the clinical significance of the equivocal cases
need to be further investigated.
PMID- 27510781
TI - [Expression and clinical significance of moesin and E-cadherin in invasive
carcinoma of breast, no specific type].
AB - OBJECTIVE: To investigate the correlation of moesin and E-cadherin with
biological behavior of breast cancer and its mechanism by comparing expression of
moesin and E-cadherin in breast invasive carcinoma of no specific type(BIC-NST),
breast ductal carcinoma in situ(BDCIS) and normal breast tissues adjacent to
carcinoma. METHODS: Breast cancer cases of the Huizhou Municipal Center People
Hospital were collected between Jan 2008 and Dec 2010, expression of moesin and E
cadherin in 104 cases of BIC-NST, 84 cases of BDCIS and 53 cases of normal breast
tissues adjacent to carcinoma were detected by tissue-microarray and SP
immunohistochemical staining. Western blot was used to detect moesin expression
of 16 BIC-NST fresh tissues. RESULTS: Expression rate of moesin in BIC-NST and
BDCIS were significantly higher than normal tissues(P<0.01), but the expression
rate of E-cadherin in BIC-NST and BDCIS were significantly lower than those of
normal tissues(P<0.01). Expression rate of moesin in BIC-NST grade III group was
significantly higher than that of the grade I group.There was a significantly
positive correlation between histological grade and moesin expression(P<0.05).
However, E-cadherin expression rate in BIC-NST grade III group was significantly
lower than that in grade I group , and there was a significantly negative
correlation between histological grade and E-cadherin expression(P<0.05).
Moreover, no significant correlation was observed between moesin and E-cadherin
expression in BDCIS tissues. Expression of moesin in clinical stage II + III BIC
NST was significantly higher than that in stage I(P<0.01) . Expression of moesin
was significantly associated with lymph node metastasis (P<0.01). But no
significant correlation was observed between moesin expression and age, tumor
size and vascular invasion . However, expression of E-cadherin in clinical stage
II+ III BIC-NST was significantly lower than that in stage I(P<0.01). Expression
of E-cadherin was significantly associated with lymph node metastasis and
vascular invasion (P<0.01). But no significant correlation was observed between E
cadherin expression, age and tumor size. There was a negative correlation between
expression of moesin and E-cadherin in BIC-NST(P=0.021)and BDCIS(P=0.032).
CONCLUSION: Higher moesin and lower E-cadherin signal transduction is closely
related to the recurrence and development of breast carcinoma, therefore moesin
and E-cadherin might provide new targets for gene therapy in breast carcinoma.
PMID- 27510782
TI - [Clinicopathologic analysis of extranodal Rosai-Dorfman disease of breast: a
report of 12 cases].
AB - OBJECTIVE: To investigate the clinicopathologic features, diagnosis and
differential diagnosis of extranodal Rosai-Dorfman disease(RDD)of the breast.
METHODS: Twelve cases of extranodal RDD of the breast were analyzed using
hematoxylin-eosin stain and immunohistochemical staining.The morphological
features and immunophenotype were observed by light microscopy, accompanied with
a review of the literature. RESULTS: Twelve cases of extranodal RDD of the breast
are presented. The patients were women and their ages ranged from 15 to 55 years
(mean =37 years). Except one patient with involvement of the right breast and
ipsilateral axillary lymph nodes, other eleven patients' disease confined to the
breast. Seven cases located in the right breast, the other five cases in the left
breast. Microscopically, it showed a typical morphology, characterized by diffuse
infiltration of large histiocytes, lymphocytes and plasmocytes that formed
irregular nodular structure with light and dark appearance under microscope.
Spindling of histiocytosis often arranged in a vague storiform with prominent
fibrosis, accumulation of foamy histiocytes and scattered atypical nuclei. The
characteristic histocytes and emperipolesis could not be seen obviously in
extranodal RDD of the breast.Immunohistochemical staining showed histocytes were
strongly positive for S-100 protein, CD68 and CD163, while negative for CD1a.
CONCLUSIONS: Extranodal RDD of the breast is very rare. Because of unconspicuous
emperipolesis and lack of specificity in clinic and images, extranodal RDD of the
breast is easy to be misdiagnosed as other histiocytosis. The microscopic
differential diagnosis includes idiopathic granulomatous mastitis, infective
granulomas, langerhans cell histiocytosis, IgG4 related sclerosing disease,
Erdheim-Chester disease, benign fibrous histiocytoma, malignant fibrous
histiocytoma and Hodgkin Lymphoma. Light and dark appearance under microscope is
the important clue in diagnosis of extranodal RDD in breast. Immunohistochemistry
is also helpful.
PMID- 27510783
TI - [Expression of long non-coding RNA MALAT1 in osteosarcoma and its effect on
invasiveness and metastatic potential of osteosarcoma cells].
AB - OBJECTIVE: To investigate the significance of long non-coding RNA MALAT1
expression in osteosarcoma, and the potential mechanism by which MALAT1 promotes
tumor metastasis. METHODS: Twenty cases of osteosarcoma in the First Affiliated
Hospital of Xinxiang Medical University and Ping Ding Shan First People's
Hospital were collected from January 2014 to December 2015. The expression of
MALAT1 in osteosarcoma tissue and paired adjacent noncancerous tissue were
analyzed by qRT-PCR. Correlation of MALAT1 expression in osteosarcoma with
clinical pathologic features was performed by the Mann-Whitney U test. U-2OS
cells were transfected with lenti-virus carrying MALAT1-shRNA and nonspecific
shRNA (LV-vector). The expression of MALAT1 was detected by qRT-PCR. The cell
activity was evaluated by MTT asssy. The impact of MALAT1-shRNA on invasion in U
2OS cells were determined by transwell migration assay. The expression of
Wnt/beta-catenin signal pathway related proteins were detected by
Immunofluorescence stain and Western blot. RESULTS: The expression level of
MALAT1 in osteosarcoma tissue was higher than that in paired adjacent
noncancerous tissue and correlated significantly with nodal and pulmonary
metastasis(P<0.01). MTT assay showed that knockdown of MALAT1 with lenti virus
MALAT1 shRNA inhibited the growth of U-2OS cells, along with marked decrease of
invasive ability of U-2OS cells in the transwell migration assay. By
immunofluorescence stain and Western blot assay, MALAT1 significantly reduced the
expression of beta-catenin, MMP7, and c-MYC in U-2OS cells. CONCLUSIONS: The
expression of MALAT1 is high in osteosarcoma and correlates with tumor
metastasis. MALAT1 promotes invasion and metastasis of osteosarcoma cells likely
thought the Wnt/beta-catenin signal pathway.
PMID- 27510784
TI - [Application of BRAF V600E mutation-specific immunohistochemistry in diagnosis of
gastrointestinal stromal tumors].
AB - OBJECTIVE: To evaluate the utility of BRAF V600E allele-specific antibody in the
diagnosis of gastrointestinal stromal tumors (GISTs). METHODS: BRAF V600E
mutation-specific immunohistochemistry and BRAF sequencing were performed in 24
consecutive GISTs, including 14 cases of KIT or PDGFRA mutations and 10 cases of
KIT/PDGFRA wild GISTs. RESULTS: GISTs of 11 men and 13 women with a mean age 54
years(range 29-75 years) were included with tumors arising from stomach (16
cases), small bowel (7 cases), and peritoneal cavity (1 case). Strong and diffuse
cytoplasmic BRAF staining was noted in 4 of 24 cases (17%), while 1 of 24 cases
(4%) showed weak staining, and 19 of 24 cases (79%) had no staining. The four
cases with strong BRAF immunostain were confirmed to have BRAF mutations,
including 3 cases in the stomach and 1 case in the small intestine. All tumors
showed spindle cell morphology. Only one case had progressive disease. No BRAF
mutations were detected in cases with weak or negative BRAF immunostain.
CONCLUSION: BRAF V600E mutation-specific immunohistochemistry is a highly
sensitive and specific marker for detecting BRAF-mutated GISTs.
PMID- 27510786
TI - [Clinicopathologic study of chordoid glioma of third ventricle: a report of 5
cases].
PMID- 27510785
TI - [ARID1A expression of SWI/SNF remodeling complex in pancreatic neuroendocrine
tumor].
AB - OBJECTIVE: To study ARID1A expression and its role in pancreatic neuroendocrine
tumors. METHODS: 51 cases of pancreatic neuroendocrine tumors were collected from
July 2003 to May 2012 from Peking Union Medical College Hospital.Eighteen normal
pancreatic tissues were used as positive control. HE staining method was used to
observe general clinicopathological features. ARID1A expression was detected
immunohistochemically by EnVision method. The relationship between ARID1A
expression and tumor grade and stage was analyzed. RESULTS: The level of ARID1A
expression was not associated with patients' gender, age, TNM stage, and tumor
size (P>0.05); but showed significantly negative correlation with tumor grade
(P<0.05). CONCLUSIONS: Low ARID1A expression was significantly related to the
high grade level of pancreatic neuroendocrine tumors. It has a certain effect on
the clinical classification of pancreatic neuroendocring tumors. ARID1A may play
a role as a tumor suppressor gene.
PMID- 27510788
TI - [Secretory carcinoma of breast in adult patient with sentinel lymph node
metastasis].
PMID- 27510787
TI - [Hyalinizing clear cell carcinoma of salivary gland: a clinicopathologic study].
PMID- 27510789
TI - [Encapsulated papillary carcinoma of breast in male patient: report of a case].
PMID- 27510790
TI - [Primary gastric aggressive fibromatosis: report of a case].
PMID- 27510791
TI - [Research progress on breast intraductal carcinoma infiltration].
PMID- 27510792
TI - [Research progress of ECRG4 genes and molecular mechanism of tumor suppressor].
PMID- 27510793
TI - [Recent progress on estrogen sulfotransferase].
PMID- 27510794
TI - Polycystic ovary syndrome.
PMID- 27510795
TI - Object Pragmatics and Language Development.
AB - The purpose of this contribution is to investigate the advent of language in the
light of the appropriation of the cultural uses of the material objects related
to material culture and the constitution of their public and shared meanings
linked to their uses. First, we suggest that the Object Pragmatics paradigm
offers a framework which allows us to take into account the uses of objects in
daily life as a site of social conventions, communication and public and shared
meanings. Second, we would like to underline the key role of the adult's
mediations in the child's ability to evolve towards linguistic development. This
contribution will discuss the notion of scenario involving primarily the object,
as a possible semiotic tool to support the child's transition to language. We
will finally illustrate that it is possible to take into consideration the
mastery of conventional uses of the object in the child's ability to engage in a
scenario and then to move towards communication and speech development. These
issues will be addressed in the context of a research project which focuses on
the observation of children interacting with an adult at 16, 20 and 24 months.
These longitudinal data were collected by video in a semi-experimental triadic
interaction design. The triadic interaction is considered as a relevant unit for
the observation and analysis of the role of material culture in speech
development, suggesting the existence of new mechanisms to be taken into account
in addition to the interactive conditions largely mentioned in literature.
PMID- 27510796
TI - Zone of Proximal Development (ZPD) as an Emergent System: A Dynamic Systems
Theory Perspective.
AB - This paper sets out to present a novel construal of one of the notions of
Vygotskian cultural-historical theory viz., zone of proximal development (ZPD)
drawing upon dynamic systems theory. The principal thesis maintains that ZDP is
an emergent and dynamic system which is engendered by a dialectical concatenation
of psychogenesic and sociogenesic facets of human development over time. It is
reasoned that Vygotskian cultural-historical theory of human development, by
invoking dialectical logic, has transcended Cartesian substance dualism and in
turn has proffered a monistic and process-anchored ontology for emerging becoming
of human consciousness. Likewise, it is contended that dynamic systems theory,
having assumed fluent flux of reality with a capital R as its ontological axiom,
entails a consilience of cognitive and contextual conceptual schemes to describe,
explain, and optimize human development. The paper concludes by drawing some
interpretive conclusions in regard to ZPD from dynamic systems theory
perspective.
PMID- 27510797
TI - Chemical modification of extracellular matrix by cold atmospheric plasma
generated reactive species affects chondrogenesis and bone formation.
AB - The goal of this study was to investigate whether cold plasma generated by
dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to
influence chondrogenesis and endochondral ossification. Replacement of cartilage
by bone during endochondral ossification is essential in fetal skeletal
development, bone growth and fracture healing. Regulation of this process by the
ECM occurs through matrix remodelling, involving a variety of cell attachment
molecules and growth factors, which influence cell morphology and protein
expression. The commercially available ECM, Matrigel, was treated with
microsecond or nanosecond pulsed (MUsp or nsp, respectively) DBD frequencies
conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant
human bone morphogenetic protein-2 was added and the mixture subcutaneously
injected into mice to simulate ectopic endochondral ossification. Two weeks
later, the masses were extracted and analysed by microcomputed tomography. A
significant increase in bone formation was observed in Matrigel treated with MUsp
DBD compared with control, while a significant decrease in bone formation was
observed for both nsp treatments. Histological and immunohistochemical analysis
showed Matrigel treated with MUsp plasma increased the number of invading cells,
the amount of vascular endothelial growth factor and chondrogenesis while the
opposite was true for Matrigel treated with nsp plasma. In support of the in vivo
Matrigel study, 10 T1/2 cells cultured in vitro on MUsp DBD-treated type I
collagen showed increased expression of adhesion proteins and activation of
survival pathways, which decreased with nsp plasma treatments. These results
indicate DBD modification of ECM can influence cellular behaviours to accelerate
or inhibit chondrogenesis and endochondral ossification. Copyright (c) 2016 John
Wiley & Sons, Ltd.
PMID- 27510799
TI - Alkali Metal Salts with Designable Aryltrifluoroborate Anions.
AB - Aryltrifluoroborate ([ArBF3](-)) has a designable basic anion structure. Various
[ArBF3](-)-based anions were synthesized to create novel alkali metal salts using
a simple and safe process. Nearly 40 novel alkali metal salts were successfully
obtained, and their physicochemical characteristics, particularly their thermal
properties, were elucidated. These salts have lower melting points than those of
simple inorganic alkali halide salts, such as KCl and LiCl, because of the weaker
interactions between the alkali metal cations and the [ArBF3](-) anions and the
anions' larger entropy. Moreover, interestingly, potassium cations were
electrochemically reduced in the potassium (meta-ethoxyphenyl)trifluoroborate
(K[m-OEtC6H4BF3]) molten salt at 433 K. These findings contribute substantially
to furthering molten salt chemistry, ionic liquid chemistry, and
electrochemistry.
PMID- 27510798
TI - Identification of extracellular miRNA in archived serum samples by next
generation sequencing from RNA extracted using multiple methods.
AB - miRNAs act as important regulators of gene expression by promoting mRNA
degradation or by attenuating protein translation. Since miRNAs are stably
expressed in bodily fluids, there is growing interest in profiling these miRNAs,
as it is minimally invasive and cost-effective as a diagnostic matrix. A
technical hurdle in studying miRNA dynamics is the ability to reliably extract
miRNA as small sample volumes and low RNA abundance create challenges for
extraction and downstream applications. The purpose of this study was to develop
a pipeline for the recovery of miRNA using small volumes of archived serum
samples. The RNA was extracted employing several widely utilized RNA isolation
kits/methods with and without addition of a carrier. The small RNA library
preparation was carried out using Illumina TruSeq small RNA kit and sequencing
was carried out using Illumina platform. A fraction of five microliters of total
RNA was used for library preparation as quantification is below the detection
limit. We were able to profile miRNA levels in serum from all the methods tested.
We found out that addition of nucleic acid based carrier molecules had higher
numbers of processed reads but it did not enhance the mapping of any miRBase
annotated sequences. However, some of the extraction procedures offer certain
advantages: RNA extracted by TRIzol seemed to align to the miRBase best;
extractions using TRIzol with carrier yielded higher miRNA-to-small RNA ratios.
Nuclease free glycogen can be carrier of choice for miRNA sequencing. Our
findings illustrate that miRNA extraction and quantification is influenced by the
choice of methodologies. Addition of nucleic acid- based carrier molecules during
extraction procedure is not a good choice when assaying miRNA using sequencing.
The careful selection of an extraction method permits the archived serum samples
to become valuable resources for high-throughput applications.
PMID- 27510800
TI - Metabolic disturbances in Chinese children with urolithiasis: a single center
report.
AB - Urinary stones and urine composition are the first steps in the process of
recurrence prevention, but data concerning the association between the two
compositions are scarce in Chinese children with urolithiasis. We retrospectively
analyzed the records of children (age range 0-18 years) with urolithiasis in our
center between March 2004 and December 2013. Stone analysis was carried out in
382 children and 24-hour urine analysis in 80 children. Analysis of both stone
and 24-hour urine composition was completed in 56 children. Stone samples were
analyzed by Fourier transform-infrared spectrometry. The major stone constituents
were calcium oxalate (78.8 %). Of 80 children with 24 h urine analysis, only 2.5
% were without urinary metabolic abnormalities. Hypocitraturia was recorded in
97.5 %, high sodium excretion in 50.0 %, cystinuria in 48.7 %, hypercalciuria in
18.8 %, small urine volumes in 12.5 %, hyperoxaluria in 5.0 % and hyperuricosuria
in 1.3 %. Interestingly, higher urine volumes were recorded in girls than in boys
(73.2 +/- 58.5 vs 51.3 +/- 45.3 mL/kg, p = 0.036). Urine sodium (p = 0.002) and
oxalate (p = 0.004) were significantly higher in children >9 year old. Moreover,
compared with calcium oxalate stone formers, the urine volume (p = 0.040),
citrate (p = 0.007) and cystine (p = 0.004) were higher in patients with cystine
stones. Hypocitraturia was the common abnormality among Chinese children with
urolithiasis. The surprisingly high incidence of cystinuria is of note.
PMID- 27510802
TI - Meaningless METS: studying the link between physical activity and health.
PMID- 27510801
TI - Structure-5-HT/D2 Receptor Affinity Relationship in a New Group of 1
Arylpiperazynylalkyl Derivatives of 8-Dialkylamino-3,7-dimethyl-1H-purine
2,6(3H,7H)-dione.
AB - In our previous papers, we have reported that some 8-amino-1,3-dimethyl-1H-purine
2,6(3H,7H)-dione derivatives possessed high affinity and displayed agonistic,
partial agonistic, or antagonistic activity for serotonin 5-HT1A and dopamine D2
receptors. In order to examine further the influence of the substituent in the
position 8 of the purine moiety and the influence of the xanthine core on the
affinity for serotonin 5-HT1A , 5-HT2A , 5-HT6 , 5-HT7 , and dopamine D2
receptors, two series of 1-arylpiperazynylalkyl derivatives of 8-amino-3,7
dimethyl-1H-purine-2,6(3H,7H)-dione were synthesized. All the final compounds
were investigated in in vitro competition binding experiments for the serotonin 5
HT1A , 5-HT2A , 5-HT6 , 5-HT7 , and dopamine D2 receptors. The structure-affinity
relationships for this group of compounds were discussed. For selected compounds,
the functional assays for the 5-HT1A and D2 receptors were carried out. The
results of the assays indicated that these groups of derivatives possessed
antagonistic activity for 5-HT1A receptors and agonistic, partial agonistic, or
antagonistic activity for D2 receptors. In total, 26 new compounds were
synthesized, 20 of which were tested in in vitro binding experiments and 5 were
tested in in vitro functional assays.
PMID- 27510803
TI - Identification of Siglec-1 null individuals infected with HIV-1.
AB - Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and
infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we
scan a large population genetic database and identify a loss-of-function variant
(Glu88Ter) that is found in ~1% of healthy people. Exome analysis and direct
genotyping of 4,233 HIV-1-infected individuals reveals two Glu88Ter homozygous
and 97 heterozygous subjects, allowing the analysis of ex vivo and in vivo
consequences of SIGLEC1 loss-of-function. Cells from these individuals are
functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and
trans-infection ex vivo. However, Siglec-1 protein truncation does not have a
measurable impact on HIV-1 acquisition or AIDS outcomes in vivo. This result
contrasts with the known in vitro functional role of Siglec-1 in HIV-1 trans
infection. Thus, it provides evidence that the classical HIV-1 infectious routes
may compensate for the lack of Siglec-1 in fuelling HIV-1 dissemination within
infected individuals.
PMID- 27510804
TI - Delivery of an Adeno-Associated Virus Vector into Cerebrospinal Fluid Attenuates
Central Nervous System Disease in Mucopolysaccharidosis Type II Mice.
AB - Mucopolysaccharidosis type II (MPS II) is a rare X-linked genetic disorder caused
by deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS), leading to
impaired catabolism of ubiquitous polysaccharides and abnormal accumulation of
these undegraded substrates in the lysosome. Like many lysosomal storage
diseases, MPS II is characterized by both somatic and central nervous system
(CNS) involvement. Intravenous enzyme replacement therapy can improve somatic
manifestations of MPS II, but systemic IDS does not cross the blood-brain barrier
and therefore cannot address CNS disease. In this study, an adeno-associated
virus serotype 9 vector carrying the IDS gene was injected into the cerebrospinal
fluid (CSF) of IDS deficient mice, a model of MPS II. Treated mice exhibited dose
dependent IDS expression and resolution of brain storage lesions, as well as
improvement in long-term memory in a novel object recognition test. These
findings suggest that delivery of adeno-associated virus vectors into CSF could
serve as a platform for efficient, long-term enzyme delivery to the CNS,
potentially addressing this critical unmet need for patients with MPS II and many
related lysosomal enzyme deficiencies.
PMID- 27510805
TI - Pickering emulsions stabilized by charged nanoparticles.
AB - The stabilization of o/w Pickering emulsions in cases of weak adsorption of solid
particles at the surface of oil droplets is addressed. Though the adsorption is
usually very strong and irreversible when partial wetting conditions are
fulfilled, electrostatic repulsions between charged solid particles act against
the adsorption. The regime of weak adsorption was reached using charged silica
nanoparticles at high pH and low ionic strength. O/w Pickering emulsions of the
diisopropyl adipate oil were stabilized by colloidal nanoparticles of Ludox(r)
AS40 consisting of non-aggregated particles of bare silica (hydrophilic). The
combination of stability assessment, droplet size and electrokinetic potential
measurements at various pH values, adsorption isotherms and cryo-SEM observations
of the adsorbed layers disclosed the specificities of the stabilization of
Pickering emulsions by adsorption of solid nanoparticles against strong
electrostatic repulsions. Not only the long-term stability of emulsions was poor
under strong electrostatic repulsions at high pH, but emulsification failed since
full dispersion of oil could not be achieved. Emulsion stability was ensured by
decreasing electrostatic repulsions by lowering the pH from 9 to 3. Stable
emulsions were stabilized by a monolayer of silica particles at 54% coverage of
the oil droplet surface at low silica content and an adsorption regime as
multilayers was reached at higher concentrations of silica although there was no
aggregation of silica in the bulk aqueous phase.
PMID- 27510806
TI - Total Synthesis of (-)-Spinosyn A via Carbonylative Macrolactonization.
AB - Spinosyn A (1), a complex natural product featuring a unique 5,6,5,12-fused
tetracyclic core structure, is the major component of spinosad, an organic
insecticide and an FDA-approved agent used worldwide. Herein, we report an
efficient total synthesis of (-)-spinosyn A with 15 steps in the longest linear
sequence and 23 steps total from readily available compounds 14 and 23. The
synthetic approach features several important catalytic transformations including
a chiral amine-catalyzed intramolecular Diels-Alder reaction to afford 22 in
excellent diastereoselectivity, a one-step gold-catalyzed propargylic acetate
rearrangement to convert 28 to alpha-iodoenone 31, an unprecedented palladium
catalyzed carbonylative Heck macrolactonization to form the 5,12-fused
macrolactone in one step, and a gold-catalyzed Yu glycosylation to install the
challenging beta-forosamine. This total synthesis is highly convergent and
modular, thus offering opportunities to synthesize spinosyn analogues in order to
address the emerging cross-resistance problems.
PMID- 27510807
TI - Improving the productivity of S-adenosyl-l-methionine by metabolic engineering in
an industrial Saccharomyces cerevisiae strain.
AB - S-Adenosyl-l-methionine (SAM) is an important metabolite having prominent roles
in treating various diseases. In order to improve the production of SAM, the
regulation of three metabolic pathways involved in SAM biosynthesis were
investigated in an industrial yeast strain ZJU001. GLC3 encoded glycogen
branching enzyme (GBE), SPE2 encoded SAM decarboxylase, as well as ERG4 and ERG6
encoded key enzymes in ergosterol biosynthesis, were knocked out in ZJU001
accordingly. The results indicated that blocking of either glycogen pathway or
SAM decarboxylation pathway could improve the SAM accumulation significantly in
ZJU001, while single disruption of either ERG4 or ERG6 gene had no obvious effect
on SAM production. Moreover, the double mutant ZJU001-GS with deletion of both
GLC3 and SPE2 genes was also constructed, which showed further improvement of SAM
accumulation. Finally, SAM2 was overexpressed in ZJU001-GS to give the best SAM
producing recombinant strain ZJU001-GS-SAM2, in which 12.47g/L SAM was produced
by following our developed pseudo-exponential fed-batch cultivation strategy,
about 81.0% increase comparing to its parent strain ZJU001. The present work laid
a solid base for large-scale SAM production with the industrial Saccharomyces
cerevisiae strain.
PMID- 27510808
TI - Engineered Upconversion Nanoparticles for Resolving Protein Interactions inside
Living Cells.
AB - Upconversion nanoparticles (UCNPs) convert near-infrared into visible light at
much lower excitation densities than those used in classic two-photon absorption
microscopy. Here, we engineered <50 nm UCNPs for application as efficient
lanthanide resonance energy transfer (LRET) donors inside living cells. By
optimizing the dopant concentrations and the core-shell structure for higher
excitation densities, we observed enhanced UCNP emission as well as strongly
increased sensitized acceptor fluorescence. For the application of these UCNPs in
complex biological environments, we developed a biocompatible surface coating
functionalized with a nanobody recognizing green fluorescent protein (GFP). Thus,
rapid and specific targeting to GFP-tagged fusion proteins in the mitochondrial
outer membrane and detection of protein interactions by LRET in living cells was
achieved.
PMID- 27510810
TI - One-year Survey of human enteroviruses from sewage and the factors affecting
virus adsorption to the suspended solids.
AB - This study described the results of environmental enterovirus surveillance
conducted in Shandong Province of China in 2013. Altogether 39 sewage samples
were collected and 873 enterovirus isolates (including 334 polioviruses)
belonging to 22 serotypes were obtained. Echovirus (E) -7, coxsackievirus (CV)
B5, E-11, E-6, and E-3 were the most commonly detected non-polio enterovirus
serotypes, and phylogeny of E-7 and CV-B5 was described. The numbers of isolates
of different serotypes from sewage supernatant were compared with those from the
solids. Interestingly, dramatic divergence was observed between the supernatant
and solids origin for the serotypes of E-3 and E-6, which were prone to the
solids and supernatant, respectively. A following adsorption test with E-3 and E
6 added sewage specimens confirmed the different preference. Furthermore, the
adsorption of Sabin poliovirus type 1 to the solids under different conditions
was investigated, and the results showed that acid medium, cold temperature, and
high solids concentration facilitated the viral adsorption to the solids, whereas
change of virus titer did not influence the proportion of adsorption. These
results highlighted the importance of combining the enterovirus isolates from the
supernatant and solids together in environmental surveillance so as to better
understand the local circulation of different serotypes.
PMID- 27510812
TI - Renal failure in dogs kept by a man with severe psoriasis.
PMID- 27510813
TI - Experiences of Prenatal Genetic Screening and Diagnostic Testing Among Pregnant
Korean Women of Advanced Maternal Age.
AB - PURPOSE: This study explored the experiences of Korean women of advanced maternal
age undergoing prenatal genetic screening and diagnostic testing. DESIGN: A
descriptive, qualitative design was used to guide the study. METHOD: Ten
participants were purposely recruited from a large metropolitan Korean hospital
for clinical observations and individual, semistructured interviews. The content
analysis method was used to analyze field notes and interview transcripts.
FINDINGS: Three themes emerged: reacting to an unfavorable screening result,
dealing with the anticipated consequences of diagnostic testing, and
realistically embracing the unborn child. CONCLUSIONS: The findings of this study
inform the development of tailored interventions aimed at reducing the heavy
emotional burdens placed on pregnant women and the stigma of bearing children
with genetic conditions. Clear reciprocal communication and shared decision
making should be promoted in the day-to-day practice of delivering health care
for pregnant Korean women.
PMID- 27510811
TI - Ca2+ transport and signalling in enamel cells.
AB - Dental enamel is one of the most remarkable examples of matrix-mediated
biomineralization. Enamel crystals form de novo in a rich extracellular
environment in a stage-dependent manner producing complex microstructural
patterns that are visually stunning. This process is orchestrated by specialized
epithelial cells known as ameloblasts which themselves undergo striking
morphological changes, switching function from a secretory role to a cell
primarily engaged in ionic transport. Ameloblasts are supported by a host of cell
types which combined represent the enamel organ. Fully mineralized enamel is the
hardest tissue found in vertebrates owing its properties partly to the unique
mixture of ionic species represented and their highly organized assembly in the
crystal lattice. Among the main elements found in enamel, Ca2+ is the most
abundant ion, yet how ameloblasts modulate Ca2+ dynamics remains poorly known.
This review describes previously proposed models for passive and active Ca2+
transport, the intracellular Ca2+ buffering systems expressed in ameloblasts and
provides an up-dated view of current models concerning Ca2+ influx and extrusion
mechanisms, where most of the recent advances have been made. We also advance a
new model for Ca2+ transport by the enamel organ.
PMID- 27510814
TI - Parenting African American Children With Autism: The Influence of Respect and
Faith in Mother, Father, Single-, and Two-Parent Care.
AB - PURPOSE: Parents are the most significant contributor to care of children with
autism spectrum disorder (ASD), and as such research on African American
parenting in ASD is conspicuously absent. Findings relevant to parenting are
discussed from a study with urban African American families caring for children
with ASD. DESIGN: An ethnonursing study was conducted with 24 African American
family members of children with ASD and 28 professionals. Data were analyzed and
reported as themes. FINDINGS: Two universal themes of were found of respect and
faith in God and family that influenced parental care. Two diverse themes of
mother's watchful care and father's protective care, along with differences in
feelings of isolation and dependence on supports were found among single- and two
parent families. DISCUSSION AND PRACTICE IMPLICATIONS: When health care
professionals increase their knowledge and understanding of cultural practices in
the parental care of children with ASD, they provide health care that is
culturally congruent.
PMID- 27510815
TI - Asymmetrical reproductive interference between two sibling species of tea looper:
Ectropis grisescens and Ectropis obliqua.
AB - Ectropis grisescens Warren and Ectropis obliqua (Prout) are two morphologically
similar sibling species with overlapping ranges. In this study, manipulative
laboratory experiments were conducted to examine the possibility of reproductive
interference in sympatric populations of E. grisescens and E. obliqua and the
potential consequences of the mating interaction. Our results showed that the
presence of males or females of different species could incur mating interference
and significant reduction of F 1 offspring. The reduction was not significant
relevant to the initial relative abundance of E. grisescens and E. obliqua.
Detailed observations of mating opportunity showed that female mating frequencies
of both species were not significantly affected by the absolute species density,
but the mating success of E. obliqua females with conspecific males depended on
species ratio. In addition, adding males to the other species resulted in lower
number of offspring suggesting that the males' behaviour might be linked with
mating interference. Males of both E. grisescens and E. obliqua could interfere
the intraspecific mating of the other species, but the impact of the mating
interference differed. These combined data indicated that asymmetric reproductive
interference existed in E. grisescens and E. obliqua under laboratory conditions,
and the offspring of the mixed species were significantly reduced. The long term
outcome of this effect is yet to be determined since additional reproductive
factors such as oviposition rate and progeny survival to adulthood may reduce the
probability of demographic displacement of one species by the other in
overlapping niches.
PMID- 27510816
TI - Safety and efficacy of rush allergen-specific immunotherapy in Chinese allergic
rhinitis patients.
AB - The purpose of this prospective, open-IV clinical trial was to assess the safety
and efficacy differences between Rush immunotherapy (RIT) and conventional
immunotherapy in Chinese allergic rhinitis (AR) patients. The trial involved 174
patients with AR. They were divided into two groups according to their preference
of therapy: RIT or conventional immunotherapy. A total of 162 patients completed
a 1-year treatment course. For safety and effectiveness evaluation, the local and
systemic adverse reactions were recorded throughout the initial phase of both
groups. Weeks 0, 2, 5, and 17 were set as observation time points for
immunoglobulin G (IgG) and IgG4. Besides that, another observation time point
(Week 11) was added in for a visual analog scale (VAS) and a weekly drug dosage
scale. In the RIT group, systemic adverse events of AR were similar to those of
the conventional therapy group. LTB4 was descended. The VAS of the RIT group did
not show a downward trend clearly, instead Week 5 was higher compared with Week
0. The weekly drug dosage scale did not indicate a significant decline, but there
was a clear rise in IgG4 in the RIT group. The safety and efficacy of RIT for AR
is positive, but further study is needed for improvement.
PMID- 27510817
TI - Kruppel-like factor 6 suppresses growth and invasion of hepatocellular carcinoma
cells in vitro and in vivo.
AB - Kruppel-like factor 6 (KLF6) as a novel tumor suppressive gene participates in
multiple biological behaviors and plays an important role in regulating tumor
cell growth and invasion. However, the functions of KLF6 in hepatocellular
carcinoma (HCC) remain poorly understood. The expression level of KLF6 was
examined by immunohistochemical assay in human HCC tissues, and KLF6
overexpressed HCC cells (SMCC-7721 and HepG2) were used for evaluating cell
proliferation and invasion by MTT and Transwell assays. A subcutaneous HCC tumor
model was established for assessing tumor growth in vivo. Our results showed that
the expression of KLF6 was significantly downregulated in HCC tissues compared
with the adjacent non-cancerous tissues (50.0% vs. 72.0%, P = 0.034) and
negatively associated with the lymph-vascular space invasion (LVSI) in HCC
patients (P = 0.003). Furthermore, overexpression of KLF6 reduced cell
proliferation and weakened the cell invasive potential followed with the
decreased expression of PCNA and MMP-9 in HCC cells. The in vivo experiment
indicated that KLF6 overexpression suppressed the xenograft tumor growth.
Therefore, our findings show that KLF6 suppresses growth and invasion of HCC
cells in vitro and in vivo, suggesting a tumor suppressive function in HCC and
provides the potential therapeutic target for the treatment of HCC.
PMID- 27510818
TI - The effect of HDL-bound and free PON1 on copper-induced LDL oxidation.
AB - Oxidative modification of LDL plays an important role in the development of
atherosclerosis. High-density lipoprotein (HDL) confers protection against
atherosclerosis and the antioxidative properties of paraoxonase 1 (PON1) has been
suggested to contribute to this effect of HDL. The PON1 exist in two major
polymorphic forms (Q and R), which regulate the concentration and activity of the
enzyme and alter its ability to prevent lipid oxidation. However, the association
of Q192R polymorphism with PON1's capacity to protect against LDL
lipoperoxidation is controversial. The aim of this study was to evaluate the
effects of the purified PON1 Q192R and the partially purified HDL-bound PON1
Q192R isoenzymes (HDL-PON1 Q192R) on LDL oxidation, with respect to their
arylesterase/homocysteine thiolactonase (HTLase) activities. Cupric ion-induced
LDL oxidation was reduced up to 48% by purified PON1 Q192, but only 33% by an
equivalent activity of PON1 R192. HDL-PON1 Q192 isoenzyme caused a 65% reduction,
whereas HDL-PON1 R192 isoenzyme caused only 46% reduction in copper ion-induced
LDL oxidation. These findings reflect the fact that PON1 Q and PON1 R allozymes
may have different protective characteristics against LDL oxidation. The
protection against LDL oxidation provided by HDL-PON1 Q192R isoenzymes is more
prominent than the purified soluble enzymes. Inhibition of the Ca(+2)-dependent
PON1 Q192R arylesterase/HTLase by the metal chelator EDTA, did not alter PON1's
ability to inhibit LDL oxidation. These studies indicate that the active site
involvement of the purified enzyme is not similar to the HDL-bound one, in terms
of both PON1 arylesterase/HTLase activity and the protection of LDL from copper
ion-induced oxidation. Moreover, PON1's ability to protect LDL from oxidation
does not seem to require calcium.
PMID- 27510819
TI - Efficient Room-Temperature Activation of Methane by TaN(+) under C-N Coupling.
AB - The thermal reaction of diatomic tantalum nitride cation [TaN](+) with methane
has been explored using FT-ICR mass spectrometry complemented by high-level
quantum chemical calculation; based on this combined experimental/computational
approach, mechanistic aspects of this novel, highly efficient C-N coupling
process have been uncovered. In distinct contrast to [TaN](+) , its lighter
congeners [VN](+) and [NbN](+) are inert towards methane under ambient
conditions, and the origins of the remarkably variable efficiencies of the three
metal nitrides are uncovered by CCSD(T) calculations.
PMID- 27510820
TI - Predictors of stereoacuity outcome in visually mature subjects with exotropia.
PMID- 27510821
TI - Conflicts over host manipulation between different parasites and pathogens:
Investigating the ecological and medical consequences.
AB - When parasites have different interests in regard to how their host should behave
this can result in a conflict over host manipulation, i.e. parasite induced
changes in host behaviour that enhance parasite fitness. Such a conflict can
result in the alteration, or even complete suppression, of one parasite's host
manipulation. Many parasites, and probably also symbionts and commensals, have
the ability to manipulate the behaviour of their host. Non-manipulating parasites
should also have an interest in host behaviour. Given the frequency of multiple
parasite infections in nature, potential conflicts of interest over host
behaviour and manipulation may be common. This review summarizes the evidence on
how parasites can alter other parasite's host manipulation. Host manipulation can
have important ecological and medical consequences. I speculate on how a conflict
over host manipulation could alter these consequences and potentially offer a new
avenue of research to ameliorate harmful consequences of host manipulation.
PMID- 27510822
TI - DL-ADR: a novel deep learning model for classifying genomic variants into adverse
drug reactions.
AB - BACKGROUND: Genomic variations are associated with the metabolism and the
occurrence of adverse reactions of many therapeutic agents. The polymorphisms on
over 2000 locations of cytochrome P450 enzymes (CYP) due to many factors such as
ethnicity, mutations, and inheritance attribute to the diversity of response and
side effects of various drugs. The associations of the single nucleotide
polymorphisms (SNPs), the internal pharmacokinetic patterns and the vulnerability
of specific adverse reactions become one of the research interests of
pharmacogenomics. The conventional genomewide association studies (GWAS) mainly
focuses on the relation of single or multiple SNPs to a specific risk factors
which are a one-to-many relation. However, there are no robust methods to
establish a many-to-many network which can combine the direct and indirect
associations between multiple SNPs and a serial of events (e.g. adverse
reactions, metabolic patterns, prognostic factors etc.). In this paper, we
present a novel deep learning model based on generative stochastic networks and
hidden Markov chain to classify the observed samples with SNPs on five loci of
two genes (CYP2D6 and CYP1A2) respectively to the vulnerable population of 14
types of adverse reactions. METHODS: A supervised deep learning model is proposed
in this study. The revised generative stochastic networks (GSN) model with
transited by the hidden Markov chain is used. The data of the training set are
collected from clinical observation. The training set is composed of 83
observations of blood samples with the genotypes respectively on CYP2D6*2, *10,
*14 and CYP1A2*1C, *1 F. The samples are genotyped by the polymerase chain
reaction (PCR) method. A hidden Markov chain is used as the transition operator
to simulate the probabilistic distribution. The model can perform learning at
lower cost compared to the conventional maximal likelihood method because the
transition distribution is conditional on the previous state of the hidden Markov
chain. A least square loss (LASSO) algorithm and a k-Nearest Neighbors (kNN)
algorithm are used as the baselines for comparison and to evaluate the
performance of our proposed deep learning model. RESULTS: There are 53 adverse
reactions reported during the observation. They are assigned to 14 categories. In
the comparison of classification accuracy, the deep learning model shows
superiority over the LASSO and kNN model with a rate over 80 %. In the comparison
of reliability, the deep learning model shows the best stability among the three
models. CONCLUSIONS: Machine learning provides a new method to explore the
complex associations among genomic variations and multiple events in
pharmacogenomics studies. The new deep learning algorithm is capable of
classifying various SNPs to the corresponding adverse reactions. We expect that
as more genomic variations are added as features and more observations are made,
the deep learning model can improve its performance and can act as a black-box
but reliable verifier for other GWAS studies.
PMID- 27510823
TI - Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update.
AB - Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique
predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This
disorder is preceded by a transient neonatal preleukaemic syndrome, transient
abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between
trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in
the key haematopoietic transcription factor gene GATA1. These mutations are found
in almost one third of DS neonates and are frequently clinically and
haematologcially 'silent'. While the majority of cases of TAM undergo spontaneous
remission, ~10 % will progress to ML-DS by acquiring transforming mutations in
additional oncogenes. Recent advances in the unique biological, cytogenetic and
molecular characteristics of TAM and ML-DS are reviewed here.
PMID- 27510824
TI - Spontaneous ovarian hyperstimulation syndrome in a young female subject with a
lingual thyroid and primary hypothyroidism.
PMID- 27510825
TI - Safety and efficacy of polyetheretherketone (PEEK) cages in combination with
posterior pedicel screw fixation in pyogenic spinal infection.
AB - BACKGROUND: To date, there is growing consensus that PEEK material may be used
for interbody fusion in spinal infections. Data supporting that claim are however
restricted to a few very small clinical series. The aim of this study is to
evaluate the outcome of surgical treatment of pyogenic spinal infections with
PEEK cages in combination with posterior pedicel screw fixation. METHODS: Between
2006 and 2013, a total of 211 patients suffering from spondylodiscitis underwent
surgical debridement and instrumentation. There were 52 cases where PEEK cages
were used. Laboratory and physical examinations were assessed at a 3-month follow
up. Last follow-up was performed with at a minimum of 12 months after surgery via
a telephone interview. RESULTS: Mean age at presentation was 67 years, with 19
(37 %) male patients and 33 (63 %) female. Distribution of the infection was
lumbar in 29 (56 %%), thoracic in 3 (6 %) and cervical in 11 (21 %) cases. Nine
patients (17 %) had concomitant non-contiguous spondylodiscitis. Epidural abscess
was found in 17 patients (33 %); 48 (92 %%) had pain; neurological deficits were
found in 20 patients (38 %). All patients in this series underwent surgical
debridement with instrumentation of the spine. Postoperative intravenous
antibiotics were administered for 15.4 +/- 6.8 days followed by 2.9 +/- 0.5
months of oral antibiotics. Complete resolution of the infection was achieved in
all cases. Of the 28 patients with neurological deficits, 6 had full recovery and
10 had improved incompletely after surgery. One patient suffered from a pulmonary
embolism postoperatively. There were no mortalities. CONCLUSIONS: Use of PEEK
cages for interbody fusion is feasible and safe in patients suffering from a
pyogenic spinal infection.
PMID- 27510826
TI - Cystic meningioma: radiological, histological, and surgical particularities in 43
patients.
AB - BACKGROUND: The presence of cysts is a rare occurrence for intracranial
meningiomas in adults. We report our experience in a large consecutive series of
cystic meningiomas. METHOD: We prospectively collected data for a dedicated
database of cystic meningioma cases between January 2004 and December 2011 in two
tertiary neurosurgical centers. Studied data included preoperative imaging,
surgical records, and pathology reports. RESULTS: Among 1214 surgeries for
intracranial meningioma, we identified 43 cases of cystic meningioma,
corresponding to an incidence of 3.5 %. The most common localization was the
hemispheric convexity (17/43 cases). Twenty-eight patients had intratumoral
cysts, nine peritumoral, and five mixed intra and extratumoral. In 29 patients
with available diffusion imaging, ADC coefficients were significantly lower in
grade II-III tumors compared to grade I (p = 0.01). Complete resection of the
cystic components was possible in 27/43 patients (63 %); partial resection in
4/43 (9 %); in 6/43 (14 %) cyst resection was not possible but multiple biopsies
were performed from the cystic walls; in another 6/43 (14 %) the cystic wall was
not identified during surgery. Cells with neoplastic features were identified
within the cyst walls at pathology in 26/43 cases (60 %). All patients were
followed-up for 24 months; long-term follow-up was available only in 32 patients
for an average period of 49 months (range, 36-96 months). No recurrence requiring
surgery was observed. CONCLUSIONS: Cystic meningiomas are rare. Cells with
neoplastic features are often identified within the cyst walls. Complete cyst
resection is recommendable when considered technically feasible and safe.
PMID- 27510827
TI - Comparison of Mechanical Disruption Techniques for Rapid Inactivation of
Mycobacterium and Nocardia Species before Identification Using Matrix-Assisted
Laser Desorption Ionization-Time of Flight (MALDI-TOF) Mass Spectrometry.
PMID- 27510828
TI - Next-Generation Sequencing: a Diagnostic One-Stop Shop for Hepatitis C?
AB - Before starting chronic hepatitis C treatment, the viral genotype/subtype has to
be accurately determined and potentially coupled with drug resistance testing.
Due to the high genetic variability of the hepatitis C virus, this can be a
demanding task that can potentially be streamlined by viral whole-genome
sequencing using next-generation sequencing as demonstrated by an article in this
issue of the Journal of Clinical Microbiology by E. Thomson, C. L. C. Ip, A.
Badhan, M. T. Christiansen, W. Adamson, et al. (J Clin Microbiol. 54:2455-2469,
2016, http://dx.doi.org/10.1128/JCM.00330-16).
PMID- 27510829
TI - Evaluation of Hologic Aptima HIV-1 Quant Dx Assay on the Panther System on HIV
Subtypes.
AB - Quantitation of the HIV-1 viral load in plasma is the current standard of care
for clinical monitoring of HIV-infected individuals undergoing antiretroviral
therapy. This study evaluated the analytical and clinical performances of the
Aptima HIV-1 Quant Dx assay (Hologic, San Diego, CA) for monitoring viral load by
using 277 well-characterized subtype samples, including 171 cultured virus
isolates and 106 plasma samples from 35 countries, representing all major HIV
subtypes, recombinants, and circulating recombinant forms (CRFs) currently in
circulation worldwide. Linearity of the Aptima assay was tested on each of 6
major HIV-1 subtypes (A, B, C, D, CRF01_AE, and CRF02_AG) and demonstrated an
R(2) value of >=0.996. The performance of the Aptima assay was also compared to
those of the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 v.2 (CAP/CTM) and Abbott
m2000 RealTime HIV-1 (RealTime) assays on all subtype samples. The Aptima assay
values averaged 0.21 log higher than the CAP/CTM values and 0.30 log higher than
the RealTime values, and the values were >0.4 log higher than CAP/CTM values for
subtypes F and G and than RealTime values for subtypes C, F, and G and CRF02_AG.
Two samples demonstrated results with >1-log differences from RealTime results.
When the data were adjusted by the average difference, 94.9% and 87.0% of Aptima
results fell within 0.5 log of the CAP/CTM and RealTime results, respectively.
The linearity and accuracy of the Aptima assay in correctly quantitating all
major HIV-1 subtypes, coupled with the completely automated format and high
throughput of the Panther system, make this system well suited for reliable
measurement of viral load in the clinical laboratory.
PMID- 27510830
TI - Malnutrition Is Associated with Protection from Rotavirus Diarrhea: Evidence from
a Longitudinal Birth Cohort Study in Bangladesh.
AB - Rotavirus is a leading cause of dehydrating diarrhea and death among infants and
children globally, particularly in communities of the developing world. While
numerous studies have described the complex relationships among infectious
diarrhea, growth faltering, and poverty, the impact of nutritional status on
susceptibility to rotavirus diarrhea is not well understood. In a longitudinal
study conducted over the first 3 years of life among 626 slum-dwelling infants
enrolled at birth in Dhaka, Bangladesh, we observed that common measures of
healthy growth and development were positively associated with a risk of
symptomatic rotavirus infection. This finding runs counter to the idea that
improving childhood nutrition will implicitly decrease the incidence of
symptomatic infection by enteric pathogens. As childhood nutrition improves
worldwide, rotavirus infection may remain a public health challenge, making
universal vaccination of even greater importance.
PMID- 27510831
TI - Assuring the Quality of Next-Generation Sequencing in Clinical Microbiology and
Public Health Laboratories.
AB - Clinical microbiology and public health laboratories are beginning to utilize
next-generation sequencing (NGS) for a range of applications. This technology has
the potential to transform the field by providing approaches that will
complement, or even replace, many conventional laboratory tests. While the
benefits of NGS are significant, the complexities of these assays require an
evolving set of standards to ensure testing quality. Regulatory and accreditation
requirements, professional guidelines, and best practices that help ensure the
quality of NGS-based tests are emerging. This review highlights currently
available standards and guidelines for the implementation of NGS in the clinical
and public health laboratory setting, and it includes considerations for NGS test
validation, quality control procedures, proficiency testing, and reference
materials.
PMID- 27510833
TI - Automatic Digital Plate Reading for Surveillance Cultures.
AB - The automation of specimen processing and culture workup has rapidly emerged in
clinical microbiology laboratories throughout the world and more recently in the
United States. While many U.S. laboratories have implemented some form of
automated specimen processing and some have begun performing digital plate
reading, automated colony analysis is just beginning to be utilized clinically.
In this issue of the Journal of Clinical Microbiology, M. L. Faron et al. (J Clin
Microbiol 54:2470-2475, 2016, http://dx.doi.org/10.1128/JCM.01040-16) report the
results of their evaluation of the performance of the WASPLab Chromogenic
Detection Module (CDM) for categorizing chromogenic agar plates as negative or
"nonnegative" for vancomycin-resistant enterococci (VRE). Their major finding was
100% sensitivity for detection of "nonnegative" specimens using CDM compared to
manual methods for specimens plated on two different types of VRE chromogenic
agar plates. Additionally, utilization of digital plate reading in conjunction
with automated colony analysis was predicted to result in significant savings
based on greatly reduced labor costs.
PMID- 27510834
TI - A review of anesthetic techniques and outcomes following minimally invasive
repair of pectus excavatum (Nuss procedure).
AB - BACKGROUND: Pectus excavatum (PE) is the most common congenital chest wall
deformity, occurring in 1 : 1000 children with a male to female ratio of 4 : 1.
Several procedures have been described to manage this deformity, including
cartilage resection with sternal osteotomy (the Ravitch procedure) and a
minimally invasive repair technique (the Nuss procedure). While initially
described as a nonthoracoscopic technique, the current surgical approach of the
Royal Childrens Hospital involves thoracoscopic assistance. Postoperative pain is
significant in patients undergoing the pectus repair and multiple analgesic
regimens have been advocated with continuous thoracic epidural infusions and
opioid infusions the most common. Some authors have advocated patient-controlled
analgesia (PCA), paravertebral nerve blocks (PVNB), and wound infusion catheters
as alternatives. AIMS: The primary aim of this study was to assess our experience
with postoperative pain and analgesia requirements associated with the minimally
invasive repair of pectus excavatum in children. METHODS: This is a retrospective
cohort study with a contemporaneous comparison group examining patients treated
between January 2005 and December 2015 for minimally invasive repair of pectus
excavatum by the Nuss procedure. RESULTS: Two hundred and seventeen patients
[mean age 14.9 (sd 1.9) years] with pectus excavatum treated at the Royal
Childrens Hospital between 2005 and 2015 were identified. All patients were
managed with thoracic epidural analgesia and intravenous morphine infusions. The
epidural was effective in the postanesthesia care unit in 97.3% (failure to place
an epidural rate was 4 (1.9%); no block on awakening 0.9%). A further 4 (1.8%)
were removed within 24 h. The mean morphine equivalent dose in the first 24 h was
0.8 mg.kg-1 .day-1 . PCA was continued for a mean of 3.8 days and the total mean
morphine equivalent dose was 2.2 mg.kg-1 .day-1 . Minor complications occurred in
67 (30.9%) with postoperative nausea and vomiting in 36 patients (16.6%) and
urinary retention requiring an indwelling catheter in 40 patients (18.4%).
CONCLUSION: An epidural-based analgesic regime is associated with low pain scores
and few acute complications. The continuation of morphine analgesia after the
first postoperative day is common but associated with an increased incidence of
urinary retention and nausea and vomiting.
PMID- 27510832
TI - KlebSeq, a Diagnostic Tool for Surveillance, Detection, and Monitoring of
Klebsiella pneumoniae.
AB - Health care-acquired infections (HAIs) kill tens of thousands of people each year
and add significantly to health care costs. Multidrug-resistant and epidemic
strains are a large proportion of HAI agents, and multidrug-resistant strains of
Klebsiella pneumoniae, a leading HAI agent, have caused an urgent public health
crisis. In the health care environment, patient colonization by K. pneumoniae
precedes infection, and transmission via colonization leads to outbreaks.
Periodic patient screening for K. pneumoniae colonization has the potential to
curb the number of HAIs. In this report, we describe the design and validation of
KlebSeq, a highly informative screening tool that detects Klebsiella species and
identifies clinically important strains and characteristics by using highly
multiplexed amplicon sequencing without a live-culturing step. We demonstrate the
utility of this tool on several complex specimen types, including urine, wound
swabs and tissue, and several types of respiratory and fecal specimens, showing
K. pneumoniae species and clonal group identification and antimicrobial
resistance and virulence profiling, including capsule typing. Use of this
amplicon sequencing tool to screen patients for Klebsiella carriage could inform
health care staff of the risk of infection and outbreak potential. KlebSeq also
serves as a model for next-generation molecular tools for public health and
health care, as expansion of this tool can be used for several other HAI agents
or applications.
PMID- 27510835
TI - Achieving value for money in health: a comparative analysis of OECD countries and
regional countries.
AB - OBJECTIVE: To measure efficiency gains in health sector over the years 1995 to
2013 in OECD, EU, non-member European countries. METHODS: An output-oriented DEA
model with variable return to scale, and residuals estimated by regression
equations were used to estimate efficiencies of health systems. Slacks for health
care outputs and inputs were calculated by using DEA multistage method of
estimating country efficiency scores. RESULTS: Better health outcomes of
countries were related with higher efficiency. Japan, France, or Sweden were
found to be peer-efficient countries when compared to other developed countries
like Germany and United States. Increasing life expectancy beyond a certain high
level becomes very difficult to achieve. Despite declining marginal productivity
of inputs on health outcomes, some developed countries and developing countries
were found to have lowered their inefficiencies in the use of health inputs.
Although there was no systematic relationship between political system of
countries and health system efficiency, the objectives of countries on social and
health policy and the way of achieving these objectives might be a factor
increasing the efficiency of health systems. CONCLUSIONS: Economic and political
stability might be as important as health expenditure in improving health system
goals. A better understanding of the value created by health expenditures,
especially in developed countries, will require analysis of specific health
interventions that can increase value for money in health. Copyright (c) 2016
John Wiley & Sons, Ltd.
PMID- 27510836
TI - Curcumin attenuates cyclosporine A-induced renal fibrosis by inhibiting
hypermethylation of the klotho promoter.
AB - Chronic kidney disease is increasingly considered to be a worldwide public health
problem and usually leads to renal fibrosis. In the present study, curcumin, a
polyphenol pigment extracted from turmeric, was demonstrated to exert protective
effects on renal fibrosis via the suppression of transforming growth factor-beta
(TGF-beta) downstream signaling, such as plasminogen activator inhibitor-1 (PAI
1), alpha-smooth muscle actin (alpha-SMA) and collagen I (Col I) downregulation.
The present findings demonstrate that curcumin exerted a protective effect on
cyclosporine A-induced renal fibrosis via a klotho (KL)-dependent mechanism,
which inhibits the TGF-beta signaling pathway. Further research indicated that
curcumin induced KL expression in HK-2 tubular epithelial cells by inhibiting CpG
hypermethylation in the KL promoter, which mediates the loss of expression in
cells. Methylation-specific polymerase chain reaction (PCR) combined with
bisulfite sequencing identified numerous key CpG sites, such as 249, 240 and 236,
whose methylation statuses are important for KL expression. A PCR reporter assay
was utilized to further confirm these findings. In addition, the effects of
curcumin on the regulation of DNA methyltransferase 1 (Dnmt1) expression were
evaluated, and the data suggest that curcumin inhibits Dnmt1 expression and
restricts CpG hypermethylation. Thus, the current study reveals that curcumin
attenuated renal fibrosis by suppressing CpG methylation in the KL promoter, thus
inducing KL expression, which inhibited TGF-beta signaling, which may provide a
novel therapeutic approach for the treatment of renal fibrosis.
PMID- 27510837
TI - Detecting default mode networks in utero by integrated 4D fMRI reconstruction and
analysis.
AB - Recently, there has been considerable interest, especially for in utero imaging,
in the detection of functional connectivity in subjects whose motion cannot be
controlled while in the MRI scanner. These cases require two advances over
current studies: (1) multiecho acquisitions and (2) post processing and
reconstruction that can deal with significant between slice motion during
multislice protocols to allow for the ability to detect temporal correlations
introduced by spatial scattering of slices into account. This article focuses on
the estimation of a spatially and temporally regular time series from motion
scattered slices of multiecho fMRI datasets using a full four-dimensional (4D)
iterative image reconstruction framework. The framework which includes
quantitative MRI methods for artifact correction is evaluated using adult studies
with and without motion to both refine parameter settings and evaluate the
analysis pipeline. ICA analysis is then applied to the 4D image reconstruction of
both adult and in utero fetal studies where resting state activity is perturbed
by motion. Results indicate quantitative improvements in reconstruction quality
when compared to the conventional 3D reconstruction approach (using simulated
adult data) and demonstrate the ability to detect the default mode network in
moving adults and fetuses with single-subject and group analysis. Hum Brain Mapp
37:4158-4178, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27510838
TI - Molecular mechanisms underlying progesterone-enhanced breast cancer cell
migration.
AB - Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle
cells (VSMCs), but to enhance migration in T47D breast cancer cells. To
investigate the mechanism responsible for this switch in P4 action, we examined
the signaling pathway responsible for the P4-induced migration enhancement in
breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated
the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in
turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA
complex in the cytosol, thereby preventing RhoA degradation, and eventually
enhanced migration in T47D cells. These findings were confirmed in the P4-treated
MCF-7. Comparing the P4-induced molecular events in between breast cancer cells
and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast
cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at
Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and
prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex
with RhoA and caused RhoA degradation in VSMCs. The results of this study
highlight the molecular mechanism underlying P4-enhanced breast cancer cell
migration, and suggest that RSK1 activation is responsible for the P4-induced
migration enhancement in breast cancer cells.
PMID- 27510839
TI - Hypolipidemic effects of HVC1 in a high cholesterol diet-induced rat model of
hyperlipidemia.
AB - HVC1, a novel formation containing four herbs, was developed and its
hypolipidemic effects in rats with high cholesterol diet (HCD)-induced
hyperlipidemia were investigated. The rats were given a HCD for 8 weeks. The HVC1
treated groups were orally administered HVC1 at doses of 10, 50 or 250 mg/kg,
respectively, and the simvastatin group was treated at a dose of 10 mg/kg. The
normal diet and HCD control groups were administered with physiological saline.
Oral administration of HVC1 (10, 50 or 250 mg/kg) significantly reduced the body
weight of rats with hyperlipidemia and regulated the total cholesterol, low
density lipoprotein cholesterol and high-density lipoprotein cholesterol levels
in the serum. In addition, tissue analysis revealed that lipid accumulation in
the liver and aorta was reduced by HVC1 administration. Furthermore, HVC1
significantly reduced the mRNA expression of peroxisome proliferator-activated
receptor-gamma, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density
lipoprotein receptor, as well as the protein level of 5' adenosine monophosphate
activated protein kinase in the liver. The results clearly demonstrate that HVC1
has a potent hypolipidemic effect, and suggest that HVC1 should be evaluated as a
potential treatment for hyperlipidemia.
PMID- 27510840
TI - Copy number variation of genes involved in the hepatitis C virus-human
interactome.
AB - Copy number variation (CNV) is a newly discovered form of intra-species genetic
polymorphism that is defined as deletions or duplications of genome segments
ranging from 1 kbp to several Mbp. CNV accounts for the majority of the genetic
variation observed in humans (CNV regions cover more than 10% of the human
genome); therefore, it may significantly influence both the phenotype and
susceptibility to various diseases. Unfortunately, the impact of CNV on a number
of diseases, including hepatitis C virus (HCV) infection, remains largely
unexplored. Here, we analyzed 421 human genes encoding proteins that have been
shown to interact with HCV proteins or genomic RNA (proteins from the HCV-human
interactome). We found that 19 of the 421 candidate genes are located in putative
CNV regions. For all of these genes, copy numbers were determined for European,
Asiatic and African populations using the multiplex ligation-dependent
amplification (MLPA) method. As a result, we identified 4 genes, IGLL1, MLLT4,
PDPK1, PPP1R13L, for which the CN-genotype ranged from 1 to 6. All of these genes
are involved in host-virus interaction; thus, their polymorphism has a potential
impact on the development of HCV infection and/or therapy outcome.
PMID- 27510841
TI - Comparison of distribution and toxicity of different types of zinc-based
nanoparticles.
AB - Zinc-based nanoparticles (Zn-NPs), mainly zinc oxide (ZnO) NPs, have promising
application in a wide area, but their potential harmful effects on environment
and human health have been continuously raised together with their high
dissolution rate. In this study, we coated the surface of ZnO NPs with phosphate
(ZnP NPs) and sulfide (ZnS NPs) which have very low solubility in water,
administered orally (0.5 and 1 mg/kg) to mice for 28 days, and then compared
their biodistribution and toxicity. As expected, ZnO NPs were rapidly ionized in
an artificial gastric fluid. On the other hand, ZnO NPs were more particlized in
an artificial intestinal fluid than ZnP and ZnS NPs. After repeated dosing, all
three types of Zn-NPs the most distributed in the spleen and thymus and altered
the level of redox reaction-related metal ions in the tissues. We also found that
three types of Zn-NPs clearly disturb tissue ion homeostasis and influence immune
regulation function. However, there were no remarkable difference in distribution
and toxicity following repeated exposure of three types of Zn-NPs, although Na+
and K+ level in the spleen and thymus were notably higher in mice exposed to ZnO
NPs compared to ZnP and ZnS NPs. Taken together, we suggest that all three types
of Zn-NPs may influence human health by disrupting homeostasis of trace elements
and ions in the tissues. In addition, the surface transformation of ZnO NPs with
phosphate and sulfide may not attenuate toxicity due to the higher particlization
rate of ZnO NPs in the intestine, at least in part. (c) 2016 Wiley Periodicals,
Inc. Environ Toxicol 32: 1363-1374, 2017.
PMID- 27510843
TI - "Adjuvant" Hyperthermic Intraperitoneal Chemotherapy: A Call to Action.
PMID- 27510842
TI - Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen
type I genes.
AB - BACKGROUND: Osteogenesis imperfecta (OI) is a heterogeneous group of disorders of
connective tissue, mainly caused by mutations in the collagen type I genes
(COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated
the association between tooth agenesis and collagen type I mutations in
individuals with OI. SUBJECTS AND METHODS: In this cohort study, 128 unrelated
individuals with OI were included. Panoramic radiographs were analyzed regarding
dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I
genes were sequenced in all individuals, and in 25, multiplex ligation-dependent
probe amplification was performed. RESULTS: Mutations in the COL1A1 and COL1A2
genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17%
(hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P =
0.016), and in those with OI type III, 47%, compared to those with OI types I,
12% (P = 0.003), and IV, 13% (P = 0.017). Seventy-five percent of the individuals
with oligodontia (>=6 missing teeth) had qualitative mutations, but there was no
association with OI type, gender, or presence of DGI. CONCLUSION: The prevalence
of tooth agenesis is high (17%) in individuals with OI, and OI caused by a
qualitative collagen I mutation is associated with oligodontia.
PMID- 27510844
TI - Comparison of Single-Incision and Conventional Multi-Port Laparoscopic Distal
Gastrectomy with D2 Lymph Node Dissection for Gastric Cancer: A Propensity Score
Matched Analysis.
AB - BACKGROUND: Single-incision laparoscopic surgery maximizes the advantages of
laparoscopic surgery by reducing abdominal trauma; however, few comparative
studies have addressed its role in gastric cancer. PURPOSE: This study sought to
demonstrate the safety and feasibility of single-incision laparoscopic distal
gastrectomy (SLDG) with radical D2 lymphadenectomy by comparing its short- and
long-term outcomes with those of conventional multi-port laparoscopic surgery
(MLDG). METHODS: From October 2007 to December 2011, we identified 175 patients
with clinical stage I-III gastric cancer who underwent SLDG with D2
lymphadenectomy (n = 90) and MLDG (n = 85) according to a review of our
prospective gastric cancer database in our institute. One-to-one propensity score
matching was performed to compare short-term outcomes and long-term survival
between the two groups. RESULTS: Mean operative time was similar between the two
groups, while blood loss was significantly lower in the SLDG group than in the
MLDG group. Postoperative recovery was faster in the SLDG group in terms of
earlier initiation of oral intake, less use of analgesics, and shorter hospital
stay. Serum C-reactive protein levels were significantly lower in the SLDG group
than in the MLDG group on postoperative days 1, 3, and 7, and the 5-year overall
survival rate was not significantly different between the two groups (93.7 vs.
87.6 %; p = 0.689). CONCLUSIONS: This study shows that SLDG with D2
lymphadenectomy is safe and feasible for gastric cancer, with better short-term
outcomes than MLDG and acceptable oncologic outcomes. Thus, SLDG may be an
attractive surgical alternative in minimally invasive surgery.
PMID- 27510845
TI - Evolving Trends Towards Minimally Invasive Surgery for Solid-Pseudopapillary
Neoplasms.
AB - BACKGROUND: Solid-pseudopapillary neoplasms are rare pancreatic neoplasms with
low malignant potential that predominantly arise in young women. We sought to
characterize this population and the evolving trend at our institution towards
laparoscopic management. METHODS: We identified all patients at our institution
that were surgically treated for solid-pseudopapillary neoplasm from 2008-2015.
Demographic and clinical information were queried from the medical record, and
descriptive statistics were performed. Student's t test and chi-square analysis
were used for comparison where appropriate. RESULTS: We identified 11 women and 1
man (average age 26 years; range 14-48 years) who were surgically treated for
solid-pseudopapillary neoplasms; 5 with distal pancreatectomy (4 open, 1
laparoscopic), 6 with pancreaticoduodenectomy (3 open, 3 laparoscopic), and 1
open enucleation. From 2008 to 2013, seven of eight (87 %) procedures were
performed open. Since 2014, three of four (75 %) procedures have successfully
been completed laparoscopically (see video clips). Length of stay was similar for
patients who had open versus laparoscopic procedures (8 vs. 9 days, p = 0.61).
Two-thirds of patients (5/8) who had open procedures experienced postoperative
complications compared with half (2/4) of patients who had laparoscopic
procedures (p = 0.28). There have been no recurrences. CONCLUSIONS: Minimally
invasive surgical management of solid-pseudopapillary neoplasms is becoming more
popular, can be performed safely, and appears to have comparable outcomes to an
open approach. Quality of life is an important metric for this relatively young
population and may be improved with a laparoscopic approach, which warrants
further investigation.
PMID- 27510846
TI - Fast Targeting and Cancer Cell Uptake of Luminescent Antibody-Nanozeolite
Bioconjugates.
AB - Understanding the targeted cellular uptake of nanomaterials is an essential step
to engineer and program functional and effective biomedical devices. In this
respect, the targeting and ultrafast uptake of zeolite nanocrystals
functionalized with Cetuximab antibodies (Ctxb) by cells overexpressing the
epidermal growth factor receptor are described here. Biochemical assays show that
the cellular uptake of the bioconjugate in the targeted cancer cells already
begins 15 min after incubation, at a rate around tenfold faster than that
observed in the negative control cells. These findings further show the role of
Ctxb exposed at the surfaces of the zeolite nanocrystals in mediating the
targeted and rapid cellular uptake. By using temperature and pharmacological
inhibitors as modulators of the internalization pathways, the results univocally
suggest a dissipative uptake mechanism of these nanomaterials, which seems to
occur using different internalization pathways, according to the targeting
properties of these nanocrystals. Owing to the ultrafast uptake process, harmless
for the cell viability, these results further pave the way for the design of
novel theranostic tools based on nanozeolites.
PMID- 27510847
TI - Competitive coordination aggregation for V-shaped [Co3] and disc-like [Co7]
complexes: synthesis, magnetic properties and catechol oxidase activity.
AB - Unique dependence on the nature of metal salt and reaction conditions for
coordination assembly reactions of varying architecture and nuclearity have been
identified in V-shaped [Co3L4] and planar disc-like [Co7L6] compounds: [CoL2(MU
L)2(MU-OH2)2(CF3CO2)2] (1) and [Co(MU-L)6(MU-OMe)6]Cl2 (2) (HL = 2-{(3
ethoxypropylimino)methyl}-6-methoxyphenol). At room temperature varying reaction
conditions, cobalt-ligand ratios and use of different bases allowed unique types
of coordination self-assembly. The synthetic marvel lies in the nature of
aggregation with respect to the two unrelated cores in 1 and 2. Complex 1 assumes
a V-shaped arrangement bound to L(-), water and a trifluoroacetate anion, while 2
grows around a central Co(II) ion surrounded by a {Co} hexagon bound to methoxide
and L(-). Magnetic measurements revealed that the intermetallic interactions are
antiferromagnetic in nature in the case of complex 1 and ferromagnetic in the
case of 2 involving high spin cobalt(ii) ions with stabilization of the high-spin
ground state in the latter case. In MeCN solutions complexes 1 and 2 showed
catalytic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBCH2) to 3,5-di-tert
butylbenzoquinone (3,5-DTBQ) in air. The kinetic study in MeCN revealed that with
respect to the catalytic turnover number (kcat) 2 is more effective than 1 for
oxidation of 3,5-DTBCH2.
PMID- 27510848
TI - Terrestrial carbohydrates support freshwater zooplankton during phytoplankton
deficiency.
AB - Freshwater food webs can be partly supported by terrestrial primary production,
often deriving from plant litter of surrounding catchment vegetation. Although
consisting mainly of poorly bioavailable lignin, with low protein and lipid
content, the carbohydrates from fallen tree leaves and shoreline vegetation may
be utilized by aquatic consumers. Here we show that during phytoplankton
deficiency, zooplankton (Daphnia magna) can benefit from terrestrial particulate
organic matter by using terrestrial-origin carbohydrates for energy and sparing
essential fatty acids and amino acids for somatic growth and reproduction.
Assimilated terrestrial-origin fatty acids from shoreline reed particles exceeded
available diet, indicating that Daphnia may convert a part of their dietary
carbohydrates to saturated fatty acids. This conversion was not observed with
birch leaf diets, which had lower carbohydrate content. Subsequent analysis of 21
boreal and subarctic lakes showed that diet of herbivorous zooplankton is mainly
based on high-quality phytoplankton rich in essential polyunsaturated fatty
acids. The proportion of low-quality diets (bacteria and terrestrial particulate
organic matter) was <28% of the assimilated carbon. Taken collectively, the
incorporation of terrestrial carbon into zooplankton was not directly related to
the concentration of terrestrial organic matter in experiments or lakes, but
rather to the low availability of phytoplankton.
PMID- 27510849
TI - Tumor-associated macrophages in human breast cancer parenchyma negatively
correlate with lymphatic metastasis after neoadjuvant chemotherapy.
AB - Breast cancer is the leading cause of cancer death in women worldwide with high
morbidity and mortality. Tumor-associated macrophages (TAM) are major innate
immune cells in the tumor microenvironment controlling primary tumor growth and
metastasis. Neoadjuvant chemotherapy (NACT) is a conventional pre-operative
treatment for breast cancer. In the present study we examined the distribution of
TAM in five distinct intratumoral morphological compartments of human breast
cancer and their correlation with clinical parameters after NACT. Our data
indicated that CD68+ but not stabilin-1+ TAM in areas with parenchymal elements
negatively correlate with lymphatic metastasis after NACT. However, in cases
where lymphatic metastases were detected (28 out of 50 analyzed samples) both
amount of CD68+ and stabilin-1+ macrophages in the areas with coarse fibrous
stroma directly correlated with the number of positive lymph nodes. In patients
with complete response to the preoperative NACT the average score of CD68
expression in the areas with coarse fibrous stroma was lower compared with cases
of a partial response and stable disease. We concluded that function of TAM after
NACT depends on their intratumoral localization and local tumor microenvironment
which plays an important role in polarization of macrophages towards tumor
suppressive or tumor-supportive types.
PMID- 27510850
TI - [Not Available].
PMID- 27510851
TI - Bayesian inference of genetic parameters for ultrasound scanning traits of
Kivircik lambs.
AB - Ultrasound scanning traits have been adapted in selection programs in many
countries to improve carcass traits for lean meat production. As the genetic
parameters of the traits interested are important for breeding programs, the
estimation of these parameters was aimed at the present investigation. The
estimated parameters were direct and maternal heritability as well as genetic
correlations between the studied traits. The traits were backfat thickness (BFT),
skin+backfat thickness (SBFT), eye muscle depth (MD) and live weights at the day
of scanning (LW). The breed investigated was Kivircik, which has a high quality
of meat. Six different multi-trait animal models were fitted to determine the
most suitable model for the data using Bayesian approach. Based on deviance
information criterion, a model that includes direct additive genetic effects,
maternal additive genetic effects, direct maternal genetic covariance and
maternal permanent environmental effects revealed to be the most appropriate for
the data, and therefore, inferences were built on the results of that model. The
direct heritability estimates for BFT, SBFT, MD and LW were 0.26, 0.26, 0.23 and
0.09, whereas the maternal heritability estimates were 0.27, 0.27, 0.24 and 0.20,
respectively. Negative genetic correlations were obtained between direct and
maternal effects for BFT, SBFT and MD. Both direct and maternal genetic
correlations between traits were favorable, whereas BFT-MD and SBFT-MD had
negligible direct genetic correlation. The highest direct and maternal genetic
correlations were between BFT and SBFT (0.39) and between MD and LW (0.48),
respectively. Our results, in general, indicated that maternal effects should be
accounted for in estimation of genetic parameters of ultrasound scanning traits
in Kivircik lambs, and SBFT can be used as a selection criterion to improve BFT.
PMID- 27510852
TI - Rapid compensatory evolution promotes the survival of conjugative plasmids.
AB - Conjugative plasmids play a vital role in bacterial adaptation through horizontal
gene transfer. Explaining how plasmids persist in host populations however is
difficult, given the high costs often associated with plasmid carriage.
Compensatory evolution to ameliorate this cost can rescue plasmids from
extinction. In a recently published study we showed that compensatory evolution
repeatedly targeted the same bacterial regulatory system, GacA/GacS, in
populations of plasmid-carrying bacteria evolving across a range of selective
environments. Mutations in these genes arose rapidly and completely eliminated
the cost of plasmid carriage. Here we extend our analysis using an individual
based model to explore the dynamics of compensatory evolution in this system. We
show that mutations which ameliorate the cost of plasmid carriage can prevent
both the loss of plasmids from the population and the fixation of accessory
traits on the bacterial chromosome. We discuss how dependent the outcome of
compensatory evolution is on the strength and availability of such mutations and
the rate at which beneficial accessory traits integrate on the host chromosome.
PMID- 27510853
TI - New strategies in myelofibrosis: the evolving paradigm of disease pathogenesis,
prognostication and treatment.
AB - Myelofibrosis (MF) is the most severe among the classical Philadelphia-negative
myeloproliferative neoplasms that also include essential thrombocytemia and
polycythemia vera. Myelofibrosis is characterized by numerous genetic lesions,
often variously associated with each other, and by an aggressive clinical
phenotype leading to severely reduced survival. Also, the inflammatory
microenvironment plays a key role in disease initiation and progression. Because
of the complexity of its pathogenesis and the variability of clinical features,
MF is a disease that requires a personalized approach and remains orphan of
curative treatments besides allogeneic transplantation. JAK2 inhibitors have
marked a remarkable progress, because they alleviate systemic symptoms and reduce
splenomegaly but have a limited effect on survival, on mutation load, and on
marrow fibrosis. Here, we review the main contributing factors to MF pathogenesis
and prognosis, focusing on how these factors relate to therapeutic choices. We
discuss results from ongoing studies of JAK2 inhibitors and report on new
therapeutic strategies that proved effective in early preclinical and clinical
trials, including combination treatments, antifibrotic agents, and telomerase
inhibitors.
PMID- 27510854
TI - T-wave morphology can distinguish healthy controls from LQTS patients.
AB - Long QT syndrome (LQTS) is an inherited disorder associated with prolongation of
the QT/QTc interval on the surface electrocardiogram (ECG) and a markedly
increased risk of sudden cardiac death due to cardiac arrhythmias. Up to 25% of
genotype-positive LQTS patients have QT/QTc intervals in the normal range. These
patients are, however, still at increased risk of life-threatening events
compared to their genotype-negative siblings. Previous studies have shown that
analysis of T-wave morphology may enhance discrimination between control and LQTS
patients. In this study we tested the hypothesis that automated analysis of T
wave morphology from Holter ECG recordings could distinguish between control and
LQTS patients with QTc values in the range 400-450 ms. Holter ECGs were obtained
from the Telemetric and Holter ECG Warehouse (THEW) database. Frequency binned
averaged ECG waveforms were obtained and extracted T-waves were fitted with a
combination of 3 sigmoid functions (upslope, downslope and switch) or two 9th
order polynomial functions (upslope and downslope). Neural network classifiers,
based on parameters obtained from the sigmoid or polynomial fits to the 1 Hz and
1.3 Hz ECG waveforms, were able to achieve up to 92% discrimination between
control and LQTS patients and 88% discrimination between LQTS1 and LQTS2
patients. When we analysed a subgroup of subjects with normal QT intervals (400
450 ms, 67 controls and 61 LQTS), T-wave morphology based parameters enabled 90%
discrimination between control and LQTS patients, compared to only 71% when the
groups were classified based on QTc alone. In summary, our Holter ECG analysis
algorithms demonstrate the feasibility of using automated analysis of T-wave
morphology to distinguish LQTS patients, even those with normal QTc, from healthy
controls.
PMID- 27510855
TI - Implications for the thalamic reticular nucleus in impaired attention and sleep
in schizophrenia.
AB - The thalamic reticular nucleus (TRN) is an inhibitory shell positioned between
the thalamus and the cortex. It is uniquely situated to modulate the flow of
sensory information from the surroundings to the cortex as well as influencing
ongoing cortical activity by modulating cortico-thalamo-cortical transmission.
Although the thinness, architecture and location of the TRN deep in the brain has
previously made this a difficult structure to study, novel optical and genetic
tools have allowed for more precise targeting of this area. Recent research has
implicated a role for the TRN in attention and sleep. Interestingly, impairments
in attention and sleep resulting from TRN perturbation are strikingly similar to
the clinical deficits observed in schizophrenia. This review aims to discuss
recent evidence for the role of TRN in attention and sleep born from optogenetic
work and connect these findings with those clinically observed in schizophrenia.
PMID- 27510856
TI - Colicins U and Y inhibit growth of Escherichia coli strains via recognition of
conserved OmpA extracellular loop 1.
AB - Interactions of colicins U and Y with the OmpA (Outer membrane protein A)
receptor molecule were studied using site-directed mutagenesis and colicin
binding assay. A systematic mutagenesis of the colicin-susceptible OmpA sequence
from Escherichia coli (OmpAEC) to the colicin-resistant OmpA sequence from
Serratia marcescens (OmpASM) was performed in regions corresponding to
extracellular OmpA loops 1-4. Susceptibility to colicins U and Y was
significantly affected by the OmpA mutation in loop 1. As with functional
analysis, a decrease in binding capacity of His-tagged colicin U was found for
recombinant OmpA with a mutated segment in loop 1 compared to control OmpAEC. To
verify the importance of the identified amino acid residues in OmpA loop 1, we
introduced loop 1 from OmpAEC into OmpASM, which resulted in the substantial
increase of susceptibility to colicins U and Y. In addition, colicins U and Y
were tested against a panel of 118 bacteriocin non-producing strains of four
Escherichia species, including E. coli (39 strains), E. fergusonii (10 strains),
E. hermannii (42 strains), and E. vulneris (27 strains). A majority (82%) of E.
coli strains was susceptible to colicins U and Y. Interestingly, colicins U and Y
also inhibited all of the 30 tested multidrug-resistant E. coli O25b-ST131
isolates. These findings, together with the fact that OmpA loop 1 is important
for bacterial virulence and is evolutionary conserved, offer the potential of
using colicins U and Y as specific anti-OmpA loop 1 directed antibacterial
proteins.
PMID- 27510857
TI - Controllably Alloyed, Low Density, Free-standing Ni-Co and Ni-Graphene Sponges
for Electrocatalytic Water Splitting.
AB - Synthesis of low cost, durable and efficient electrocatalysts that support oxygen
evolution reaction (OER) and hydrogen evolution reaction (HER) are the
bottlenecks in water electrolysis. Here we propose a strategy for the development
of controllably alloyed, porous, and low density nickel (Ni) and cobalt (Co)
based alloys - whose electrocatalytic properties can be tuned to make them
multifunctional. Ni and Co based alloy with the chemical structure of Ni1Co2 is
identified as an efficient OER catalyst among other stoichiometric structures in
terms of over potential @ 10 mAcm(-2) (1.629 V), stability, low tafel slope (87.3
mV/dec), and high Faradaic efficiency (92%), and its OER performance is also
found to be on par with the benchmarked IrO2. Tunability in the porous metal
synthesis strategy allowed the incorporation of graphene during the Ni sponge
formation, and the Ni- incorporated nitrogen doped graphene sponge (Ni-NG) is
found to have very high HER activity. A water electrolysis cell fabricated and
demonstrated with these freestanding electrodes is found to have high stability
(>10 hours) and large current density (10 mAcm(-2) @ 1.6 V), opening new avenues
in the design and development of cost effective and light weight energy devices.
PMID- 27510858
TI - Ozone/graphene oxide catalytic oxidation: a novel method to degrade emerging
organic contaminant N, N-diethyl-m-toluamide (DEET).
AB - N, N-diethyl-m-toluamide (DEET) is one of the important emerging contaminants
that are being increasingly detected in reclaimed water as well as in drinking
water sources. However, DEET is refractory to conventional biological treatment
and pure ozone which is absent of hydroxyl radical. Current researches on the
efficient removal of DEET are still quite limited. This study utilizes a novel
method, namely ozone/graphene oxide (O3/GO), to investigate the effects on DEET
removal in aqueous systems, especially in reclaimed water. The results indicate
that the DEET degradation rate was significantly accelerated through the combined
effect of GO and ozonation which can yield abundant hydroxyl radical, compared to
pure ozone condition. According to hydroxyl radical scavenging experiments,
hydroxyl radical was found to play a dominant role in synergistic removal of
DEET. These findings can offer sound suggestions for future research on the
removal of emerging organic contaminants. The information could also be
beneficial to reclaimed water safety and sustainable management.
PMID- 27510859
TI - The peculiar behavior of the molecular dynamics of a glass-forming liquid
confined in native porous materials - the role of negative pressure.
AB - In this paper, we combine Broadband Dielectric Spectroscopy (BDS) at ambient and
high pressure, and positron annihilation lifetime spectroscopy (PALS) data of 2
ethylhexanol in the bulk state and when infiltrated in native silica nanopores to
elucidate the relative role of surface effects on the Debye and structural
relaxation processes under 2D spatial constraints. We show that the two processes
have different sensitivities to (i) the changes in density as quantified by the
EV/Hp ratio and (ii) the degree of confinement. Significant enhancement of the
dynamics of the confined molecules at low temperatures is related to the
vitrification of the interfacial molecules (Tg,int) affecting the packing density
of the core molecules. This is corroborated by the PALS measurements, which
demonstrated that the effective volume for the confined samples is slightly
higher and seems to be temperature invariant below Tg,int. Consequently, negative
pressure systematically develops with lowering temperature reaching values of
100 and -110 MPa (depending on the pore size) at the glass transition
temperature. This result offers a better understanding of the counterbalance
between surface and finite size effects as well as the role of negative pressure
in controlling the dynamics and the glass transition of liquids under 2D spatial
restrictions.
PMID- 27510860
TI - Acute ammonia toxicity in crucian carp Carassius auratus and effects of taurine
on hyperammonemia.
AB - The four experimental groups were carried out to test the response of crucian
carp Carassius auratus to ammonia toxicity and taurine: group 1 was injected with
NaCl, group 2 was injected with ammonium acetate, group 3 was injected with
ammonium acetate and taurine, and group 4 was injected with taurine. Fish in
group 2 had the highest ammonia and glutamine contents, and the lowest glutamate
content in liver and brain. Serum superoxide dismutase (SOD), glutathione (GSH)
activities, red cell count (RBC), white cell count (WBC), lysozyme (LYZ)
activity, complement C3 content of fish in group 2 reflected the lowest, but
malondialdehyde content was the highest. Importantly, serum SOD and GSH
activites, RBC, WBC, and LYZ activity, C3, C4 and total immunoglobulin contents
of fish in group 3 were significantly higher than those of fish in group 2. This
study indicates that ammonia exerts its toxic effects by interfering with amino
acid transport, inducing ROS generation, leading to malondialdehyde accumulation
and immunosuppression of crucian carp. The exogenous taurine could mitigate the
adverse effect of high ammonia level on fish physiological disorder.
PMID- 27510861
TI - A bit of a mouthful.
AB - This month's Genome Watch explores recent advances in the identification of
species-level and strain-level diversity in microbiome studies, and highlights
how these have provided insights into the tropism and persistence of Neisseria
spp. in the human oral cavity.
PMID- 27510862
TI - The physiology of growth arrest: uniting molecular and environmental
microbiology.
AB - Most bacteria spend the majority of their time in prolonged states of very low
metabolic activity and little or no growth, in which electron donors, electron
acceptors and/or nutrients are limited, but cells are poised to undergo rapid
division cycles when resources become available. These non-growing states are far
less studied than other growth states, which leaves many questions regarding
basic bacterial physiology unanswered. In this Review, we discuss findings from a
small but diverse set of systems that have been used to investigate how growth
arrested bacteria adjust metabolism, regulate transcription and translation, and
maintain their chromosomes. We highlight major questions that remain to be
addressed, and suggest that progress in answering them will be aided by recent
methodological advances and by dialectic between environmental and molecular
microbiology perspectives.
PMID- 27510863
TI - Biofilms: an emergent form of bacterial life.
AB - Bacterial biofilms are formed by communities that are embedded in a self-produced
matrix of extracellular polymeric substances (EPS). Importantly, bacteria in
biofilms exhibit a set of 'emergent properties' that differ substantially from
free-living bacterial cells. In this Review, we consider the fundamental role of
the biofilm matrix in establishing the emergent properties of biofilms,
describing how the characteristic features of biofilms - such as social
cooperation, resource capture and enhanced survival of exposure to antimicrobials
- all rely on the structural and functional properties of the matrix. Finally, we
highlight the value of an ecological perspective in the study of the emergent
properties of biofilms, which enables an appreciation of the ecological success
of biofilms as habitat formers and, more generally, as a bacterial lifestyle.
PMID- 27510865
TI - [Attach importance to diseases associated with severe Epstein-Barr virus
infection in children].
PMID- 27510864
TI - Quorum sensing signal-response systems in Gram-negative bacteria.
AB - Bacteria use quorum sensing to orchestrate gene expression programmes that
underlie collective behaviours. Quorum sensing relies on the production, release,
detection and group-level response to extracellular signalling molecules, which
are called autoinducers. Recent work has discovered new autoinducers in Gram
negative bacteria, shown how these molecules are recognized by cognate receptors,
revealed new regulatory components that are embedded in canonical signalling
circuits and identified novel regulatory network designs. In this Review we
examine how, together, these features of quorum sensing signal-response systems
combine to control collective behaviours in Gram-negative bacteria and we discuss
the implications for host-microbial associations and antibacterial therapy.
PMID- 27510866
TI - [Principle suggestions for diagnosis and treatment of main nontumorous Epstein
Barr virus-associated diseases in children].
PMID- 27510867
TI - [Consensus statement on diagnosis and treatment of congenital adrenal hyperplasia
due to 21-hydroxylase deficiency].
PMID- 27510868
TI - [An analysis of 181 cases with blood stream infection caused by Streptococcus
agalactiae in children from 2011 to 2015: a multi-center retrospective study].
AB - OBJECTIVE: To analyze the clinical characteristics of blood stream infection
caused by Streptococcus agalactiae in children and the drug-resistance of the
isolates. METHOD: All cases with Streptococcus agalactiae growth in blood or
cerebrospinal fluid cultures from January 1, 2011 to December 31, 2015 were
enrolled by checking the laboratory information system (LIS) from 7 Class 3 Grade
A hospitals (4 in Zhejiang, 2 in Shanghai and 1 in Chongqing). Clinical data were
collected for analysis. chi(2) test, t test and non parametric test were used in
the study. RESULT: One hundred and eighty-one pediatric cases of blood stream
infection caused by Streptococcus agalactiae were included in current study.
Eighty-six cases (47.5%) were male, and with age range from one day to 9 years
(media 13 days). Thirty cases (16.6%) were premature infants and 127 cases
(70.2%) were born via vaginal delivery. Seventy-one cases (39.2%) had early onset
(<7 d) infections, and 106 cases (58.6%) had late onset (7-89 d) infections.
Seventy-eight cases (43.1%) were complicated with purulent meningitis. Incidences
of vaginal delivery(81.7%(58/71) vs. 62.3%(66/106)), shortness of breath moaning
(43.7%(31/71) vs. 15.1%(16/106)) and preterm premature rupture of membranes
(25.4%(18/71) vs. 3.8%(4/106)) were higher in the early onset infection group
compared with the late onset group(P all<0.05). However, the number of cases who
had fever(25.4%(18/71)vs.85.8%(91/106)) and complicated with purulent meningitis
(29.6%(21/71) vs. 53.8%(57/106)) in early onset infections group was less than
that in the late onset group(P both<0.05). The blood cultures of most patients
(87.8%) were performed before the use of antibiotics. Drug-resistant tests showed
that the sensitive rates to penicillin G, ceftriaxone and cefotaxime were 98.9%,
99.0% and 99.0% respectively. All strains were sensitive to vancomucine. The
rates of resistance to clindamycin and erythromycin were 68.0% and 34.0%,
respectively. Only 39 cases (22.0%) were treated with single antibiotics of
either penicillins or cephalosporins, 80 cases (45.2%) were treated with
antibiotics containing beta lactamase inhibitor, 61 cases (34.5%) were treated
with either meropenem or cefoperazone-sulbactam. One hundred and fifty-four cases
were cured, while 19 died (including 13 complicated with purulent meningitis) and
8 lost to follow up after giving up of treatment. CONCLUSION: The incidence and
mortality of blood stream infection caused by Streptococcus agalactiae
complicated with purulent meningitis are high in children. Penicillin is the
first choice in treatment. Antibiotics should be selected accorrding to the drug
resistance test.
PMID- 27510869
TI - [Prevalence characteristics of influenza viruses in children in Beijing during
2014-2015 and 2015-2016 influenza seasons].
AB - OBJECTIVE: To compare the prevalence characteristics of influenza viruses in
children in Beijing during 2014-2015 and 2015-2016 influenza seasons. METHOD:
Throat swabs were collected weekly from children with influenza-like illnesses
who visited in Children's Hospital affiliated to Capital Institute of Pediatrics
during the period from September 2014 to May 2016.Influenza viruses A and B
viruses were detected by real-time RT-PCR, followed by identification of H3N2,
H1N1pdm, B/Victoria-like and B/Yamagata-like.The prevalence characteristics of
influenza viruses was estimated by means of descriptive statistics.The t test and
chi-square test were used to compare median age and gender ratio of infected
children among different types of influenza viruses. RESULT: Out of 1 821 throat
swabs collected, 139 (7.6%) were positive for H3N2 and 43 (2.4%) for H1N1pdm and
204 (11.2%) for influenza B virus, including 108 for B/Victoria-like and 96 for
B/Yamagata-like.The median age of H1N1pdm infected children ((3.3+/-2.2) years)
was significantly younger than that of H3N2 ((4.7+/-3.2) years) and influenza B
virus((4.9+/-2.8) years) (H1N1pdm vs. H3N2: t=2.848, P=0.002; H1N1pdm vs.
influenza B, t=3.682, P=0.000). Two epidemic peaks were presented in 2014-2015
influenza season, dominated definitely by H3N2 and B/Yamagata-like, respectively,
while one delayed peak started at the 51(st) week, 2015, co-circulated with H3N2,
H1N1pdm and influenza B viruses, among which B/Victoria-like virus was
predominant during the 2015-2016 season. CONCLUSION: Prevalence characteristics
of influenza viruses are different between 2014-2015 and 2015-2016 influenza
seasonal epidemics in children in Beijing. It is important to monitor the genetic
variations of influenza viruses and to keep close attention to influenza B virus
as well as influenza A virus.
PMID- 27510870
TI - [A retrospective study on the liver pathological characteristics and the effect
of antiviral treatment for 1 to 7 years old children with heptitis B e antigen
negative chronic hepatitis B].
AB - OBJECTIVE: To investigate the liver pathological characteristics and the
clearance rate of hepatitis B surface antigen (HBsAg) with antiviral treatment
for 1 to 7 years old children with heptitis B e antigen(HBeAg)-negative chronic
hepatitis B. METHOD: A total of 49 cases with HBeAg-negative chronic hepatitis B
were treated with interferon (IFN) or IFN treatment for 6 months added with
lamivudine, and were followed up for at least 6 months.Retrospective analysis was
performed on the liver pathological characteristics, the efficacy of antivirus
treatment and its influencing factors of the HBsAg clearance rate in the cases
from June 2006 to December 2013 in the 302 Hospital of People's Liberation
Army.The chi(2) test was used to compare the rates. RESULT: (1)The median age of
cases was 3 years old(1-7 years old), 38 children were male(78%). Cases in the
age group 1-2, >2 -3, >3 -4, >4-5, >5-6 and >6-7 were 7, 8, 14, 6, 6 and 8
respectively. HBsAg was 100% positive in mother of the cases. (2)There were 7
children whose pre-treatment alanine aminotransferase (ALT) were <=80 U/L and pre
treatment ALT>200 U/L in 25 children. There were 24 children whose pre-treatment
HBVDNA >=1*10(7) U/ml. Genetype analysis was detected in 43 children, 3 children
were B genotype, 38 were C genotype, 2 were B and C genotype. (3)Liver biopsy was
performed in all children. The degree of liver inflammation >=2 was seen in 48
(98%) children.Severe liver fibrosis and cirrhosis were found in 21(43%)
children. (4)In the age group 1-2, >2-3, >3-4, >4-5, >5-6 and >6-7 years old ,
the clearance of HBsAg was 5, 6, 2, 1, 0 and 0 respectively. The HBsAg clearance
rate between 1-3 years old group and 3-7 years old group has significant
difference ((73%(11/15) vs. 9%(3/34), chi(2)=18.180, P=0.000). (5)The clearance
of HBsAg in male group was 11, but 3 in female group.It showed no significant
difference between two groups (chi(2)=0.073, P=0.787). (6) The clearance rate of
HBsAg were 0, 24%(4/17) and 40%(10/25) in the groups of pre-treatment ALT <=80
U/L, 80200 U/L, respectively. There were no significant
difference between the groups of ALT<=200 U/L and ALT > 200 U/L(chi(2)=2.223,
P=0.136). In the groups with pre-treatment HBV DNA <1*10(7)U/ml and HBV
DNA>=1*10(7)U/ml, the clearance rate of HBsAg was 28%(7/25) and 29%(7/24). There
were no significant elifference between two groups(chi(2)=0.008, P=0.928). (7)The
clearance rate of HBsAg was 33%(7/21) in children with severe liver fibrosis and
cirrhosis, while 25%(7/28) in children who had no severe liver fibrosis and
cirrhosis.There were no significant difference between two groups(chi(2)=0.408,
P=0.523). CONCLUSION: There are obvious liver injuries and severe liver fibrosis
in 1-7 years old children with HBeAg-negative chronic hepatitis B. The HBsAg
clearance rate in the children with antiviral treatment correlated with age,
among those who received antiviral treatment before 3 years old, the HBsAg
clearance rate is relatively higher.
PMID- 27510871
TI - [Clinical and genetic characteristics and detection of urinary pipecolic acid in
pyridoxine dependent epilepsy].
AB - OBJECTIVE: To analyze the clinical and genetic characteristics of patients with
pyridoxine dependent epilepsy (PDE), and build a method to detect and analyze the
concentration of urinary pipecolic acid in PDE patients receiving pyridoxine
treatment. METHOD: Twelve patients (8 were male, 4 were female) were diagnosed as
PDE in Peking University First Hospital between April 2012 and September 2015.
The clinical manifestations, diagnosis and treatment process, video
electroencephalogram, magnetic resonance imaging were retrospectively analyzed.
ALDH7A1 gene was detected using Sanger sequencing or targeted next-generation
sequencing. The concentration of urinary pipecolic acid in PDE patients was
detected with gas chromatography-mass spectrometry (GC-MS), as well as in some
non-PDE children served as normal control. All controls, 58 cases totally, were
neonates born in our hospital or children came to our hospital for reasons such
as syncope (without disturbing pipecolic acid metabolism) from November 2015 to
January 2016. Of them, 25 were <=6 months old(14 were male, 11 were female), 33
were >6 months old(14 were male, 19 were female). The Student's t-test or Mann
Whitney U test was used for comparing the pipecolic acid between the two groups.
Correlation analysis was conducted using Pearson or Spearman test. RESULT: Of the
12 patients, seven of them were abnormal at birth. The age of epilepsy onset was
from 5 h to 5 months, within 10 d in 8 patients. After a diagnostic delay time of
15 d to 20 months, seizures in all patients were controlled by pyridoxine
monotherapy, at a dose of higher than 10.0 mg/(kg.d) in 10 patients, and 8.5 and
2.5 mg/(kg.d) in the other 2 patients respectively. The range of maintenance dose
was 2.5-20.0 mg/(kg.d) during the follow up. Interictal electroencephalogram
showed nonspecific abnormality in 10, normal in 2. Brain magnetic resonance
imaging showed nonspecific abnormality in 7, normal in 5. ALDH7A1 mutations were
found in all patients, including 15 different mutation sites, four of which were
never reported before. Splicing mutation IVS11+ 1G>A was carried in 6 patients,
with a frequency of 25% (6/24). At the last follow-up, eleven patients were in
various degree of psychomotor development delay, including the 4 patients with
severe delay in whom birth abnormalities presented, and no significant delay was
found in one patient. The concentration of urinary pipecolic acid in control: age
<=6 months, median 8.47 (0.46-35.33) mmol/mol creatinine; age >6 months, median
0.66 (0.12-3.52) mmol/mol creatinine. The concentration of urinary pipecolic acid
was different between two groups of control (Z=-5.464, P<0.01). Twelve patients
were all older than 6 months when they were tested, and the concentration was
only mildly elevated in one patient, the range of 12 patients was 0.14-4.08
mmol/mol creatinine. The concentration was not significantly different between
the control with age >6 months and our PDE patients (Z=-0.655, P>0.05). There
were no significant correlations between the concentration of urinary pipecolic
acid and the initial dose or maintenance dose at last follow-up of pyridoxine
(r=0.418 and 0.166, P=0.176 and 0.607). CONCLUSION: Seizures start in early
infancy in most PDE patients. The splicing mutation IVS11+ 1G>A is supposed to be
a probable"hotspot"mutation with a high frequency in Chinese PDE patients. Most
patients have different levels of psychomotor development delay after seizures
are controlled, and the patients with birth abnormalities may have worse
outcomes. No relationships between the diagnostic delay time and the development
outcome are found. The concentration of urinary pipecolic acid can return to
normal during treatment with pyridoxine.
PMID- 27510872
TI - [Evaluation of an automatic image-based screening technique for neonatal
hyperbilirubinemia].
AB - OBJECTIVE: To verify the accuracy of a smart phone software application, which is
an automated image-based bilirubin (AIB) testing technique for testing peripheral
blood total bilirubin (TB) in term and late preterm neonates. METHOD: During July
2015 to January 2016, jaundiced neonates were enrolled from department of
neonatology in Tongji Hospital, Children's Hospital of Zhejiang University School
of Medicine and Shenzhen Bao'an Maternal and Child Health Hospital. The enrolling
criteria included gestational age (GA)>=34 weeks and peripheral blood total
bilirubin test is required. Near-simultaneous TB, transcutaneous bilirubin (TcB),
and AIB were determined. AIB consists of a cloud based off-line learning module
and an on-line prediction module. Skin image, by smart phone is uploaded to a
specific cloud server that includes learning based software to provide an
individualized and immediate predicted bilirubin index. The t-test was used to
determine if AIB and peripheral blood TB are significantly different. Agreement
of AIB and TcB were compared with peripheral blood TB by Bland-Altman analysis.
Linear regression was adopted to model the relationship of AIB and peripheral
blood TB. The ROC curve of AIB was also plotted. RESULT: Two hundred and fifteen
neonates were enrolled, gestational age 37 weeks+ 5 d, postnatal age (11+/-4) d,
weight (2.9+/-0.7) kg, 116 male and 99 female. One hundred and forty-eight term
neonates (GA>=37 weeks) and 67 preterm neonates (GA 34-<37 weeks) were enrolled
in this study. There was no significant difference between AIB (197+/-51)MUmol/L
and peripheral blood TB(191+/-65)MUmol/L (t=1.611, P=0.109). There was strong
relevance between peripheral blood TB and AIB as shown by Bland-Altman analysis
(96% (207/215) samples lay within the 95% limits of agreement). The regression
analysis showed that the r(2) was 0.593 in the whole population, while the r(2)
was 0.628 in the term neonates. The ROC of AIB yielded a 0.743 AUC, and with 82%
sensitivity and 60% specificity based on Youden index criterion. CONCLUSION:
Based on AIB's agreement with peripheral blood TB, the sensitivity and
specificity, AIB can be used as a new technique to provide results for objective
follow-up for progression and regression of jaundice.
PMID- 27510873
TI - [Complications of critically ill children supported by venoarterial
extracorporeal membrane oxygenation].
AB - OBJECTIVE: To study the complications occurred in the process of venoarterial
extracorporeal membrane oxygenation (VA-EMCO) in critically ill children. METHOD:
To analyze retrospectively 25 children who were admitted to PICU of Children's
Hospital of Fudan University from December 2011 to December 2015. They were all
treated with VA-ECMO with incision and catheterization in right internal carotid
artery and jugular vein. Complications were recorded during ECMO process. RESULT:
The duration of ECMO treatment was 14 to 567 h (153 (112, 204) h). Seventeen
cases (68%) withdrew from ECMO successfully and 15 cases (60%) survived to
discharge. Thirty-three complications occurred during ECMO treatment. Of which,
mechanical complications occurred 9 times, including oxygenator leakage (n=3),
hemolysis (n=2), water tank failure (n=2), pump head rupture (n=1) and piping
thrombosis (n=1). Somatic complications appeared 24 times, including neurological
complications (n=8) which included cerebral infarction (n=2), convulsions (n=2),
intracranial hemorrhage (n=2), thrombosis after ligation of internal jugular vein
(n=1) and cerebral atrophy (n=1); bleeding complications (n=8) which included
bleeding at puncture sites (n=4), ECMO canalized site bleeding (n=3), and
spontaneous (n=1), intracranial hemorrhage or hematoma cases(n=2) in mechanical
complications; acute kidney injury (n=5) and microcirculation thrombosis (n=3).
CONCLUSION: ECMO technique may cause complications, which mainly include
neurological, mechanical and clotting complications. Advanced equipments and
materials and well-managed teamwork are helpful in decreasing complications.
PMID- 27510874
TI - [Application of the computer-based respiratory sound analysis system based on Mel
frequency cepstral coefficient and dynamic time warping in healthy children].
AB - OBJECTIVE: We designed a computer-based respiratory sound analysis system to
identify pediatric normal lung sound. To verify the validity of the computer
based respiratory sound analysis system. METHOD: First we downloaded the standard
lung sounds from the network database (website: http:
//www.easyauscultation.com/lung-sounds-reference-guide) and recorded 3 samples of
abnormal loud sound (rhonchi, wheeze and crackles) from three patients of The
Department of Pediatrics, the First Affiliated Hospital of Xiamen University. We
regarded such lung sounds as"reference lung sounds". The"test lung sounds"were
recorded from 29 children form Kindergarten of Xiamen University. we recorded
lung sound by portable electronic stethoscope and valid lung sounds were selected
by manual identification. We introduced Mel-frequency cepstral coefficient (MFCC)
to extract lung sound features and dynamic time warping (DTW) for signal
classification. RESULT: We had 39 standard lung sounds, recorded 58 test lung
sounds. This computer-based respiratory sound analysis system was carried out in
58 lung sound recognition, correct identification of 52 times, error
identification 6 times. Accuracy was 89.7%. CONCLUSION: Based on MFCC and DTW,
our computer-based respiratory sound analysis system can effectively identify
healthy lung sounds of children (accuracy can reach 89.7%), fully embodies the
reliability of the lung sounds analysis system.
PMID- 27510875
TI - [Clinical and pathological analysis of IgA nephropathy with acute kidney injury].
AB - OBJECTIVE: To investigate the incidence, etiology, clinico- pathological
characteristics and prognosis in primary IgA nephropathy (IgAN) children with
acute kidney injury (AKI). METHOD: Retrospective analysis of the clinical and
pathological manifestations and follow-up results of 19 Chlidren, who were
associated with AKI in 196 cases of children with IgA nephropathy treated in our
department from January, 1996 to Jun, 2012 was performed. RESULT: (1) The 19
cases associated with AKI accounted for 9.7% of all 196 Chlidren with IgAN.
Within the 19 cases, there were gross hematuria in 17 cases, massive proteinuria
in 16 cases, hypoalbuminemia in 10 cases, edema in 10 cases and hypertension in
one case. The peak serum creatinine was from 94.5 MUmol/ L to 282 MUmol/L. (2)
Histological changes: with the formation of crescent in 10 cases, diffuse
endocapillary proliferation in 5 cases, 15 cases had renal tubular injury, 10
cases had red blood cell and protein cast, 1 case with acute interstitial
nephritis. (3) The cause of IgA nephropathy with AKI: 13 patients had severe
glomerular damage, including crescentic glomerulonephritis and diffuse
endocapillary proliferation; 1 case was complicated with acute interstitial
nephritis after being treated with antibiotics, 2 patients had decreased
glomerular filtration rate because of taking benazepril or oral indomethacin, 1
case with renal tubular injury induced by gross hematuria, and the other two
cases the reason was not clear. (4) Multivariate Logistic regression analysis
showed that massive proteinuria was independent risk factor of IgAN in children
with AKI (OR=27.370, 95% confidence interval was 3.151-237.740, P<0.01). (5) None
of the patients were on dialysis, steroid therapy was used in 13 cases (including
7 cases of methylprednisolone pulse therapy), 6 cases were treated with combined
cyclophosphamide treatment. Except 1 cases no significant improvement, the renal
functiones of all patients recovered or improved within 1-2 months after
treatment. Follow-up period was from 1 month to 7 years, 3 cases had renal
function improved, but 2 cases were lost to follow-up for 3 years and then
entered the chronic renal failure, 1 case had renal function loss after 32 months
and repeated renal biopsy showed glomerular sclerosis of 32% during the follow-up
period. CONCLUSION: In children with IgAN, AKI accounted for about 10%, except
glomerular severe lesion, the onset of AKI is also relevant to clinical
medication and repeated gross hematuria, and the heavy proteinuria is an
independent risk factor. Based on clinical observation, the short-term prognosis
of IgAN children with AKI is optimistic.
PMID- 27510876
TI - [A major histocompatibility complex class II deficiency case report and
literature review].
AB - OBJECTIVE: To summarize and report the clinical characteristics and laboratory
results of a case and those reported in literature with MHC class II deficiency.
METHOD: The clinical features, laboratory results and gene mutation analysis of
an infant with MHC class II deficiency, who was diagnosed and treated in Peking
Union Medical College Hospital since December 2013, were retrospectively
analyzed."Major histocompatibility complex class II deficiency"or"bare lymphocyte
syndrome"were used as keywords in order to retrieve reports from CNKI (from its
establishment to October 2015) and Wanfang Database (from its establishment to
October 2015), PubMed Database (from its establishment to October 2015) was
searched. The characteristics, diagnosis, treatment and prognosis were summarized
by reviewing related articles. RESULT: The patient was a 8-month-old boy. Since
the fourth month of life, he started to have repeated fever, susceptible to a
variety of pathogens, immune hemolytic anemia, severe malnutrition, and finally
diagnosed as MHC class II deficiency disease when he was 20-month-old.No related
reports were retrieved from CNKI and Wanfang database, there were 20 articles and
179 patients were reported worldwide in the past 10 years. Patients exhibit an
extreme vulnerability to infections(resptratory infection(82%, 146/178),
inpection of gastroin testinal(76%, 135/178)). The common laboratory examinations
showed hypogammaglobulinemia, CD4(+) lymphopenia(93%, 107/115) etc. Diagnosis
relies on the flow-cytometric analysis and genetic analysis. CONCLUSION: It is
considered necessary for patients with young onset age, manifestation of
clinically opportunistic infection as immune deficient disease, including the MHC
class II deficiency disease, especially long-term diarrhea, poor development and
cryptosporidium infection. This disease could coexist with autoimmune disorders.
PMID- 27510877
TI - [Clinical and genetic analysis of an infant with isolated 17, 20-lyase
deficiency].
AB - OBJECTIVE: To explore the clinical and genetic characteristics of an infant with
isolated 17, 20-lyase deficiency. METHOD: The clinical, biochemical and genetic
characteristics were analyzed in an 8-month-old infant with 46, XY gonadal
dysgenesis who presented predominantly the female external genitalia. RESULT: The
infant was referred because of"masses in bilateral inguinal region and 46, XY
gonadal dysgenesis". He was normotensive. Laboratory tests revealed elevated
levels of progesterone and 17-hydroxyprogesterone. The detailed parameters are as
follows: progesterone 29.35(reference range 0.09-1.0)nmol/L, 17
hydroxyprogesterone 10.9(reference range 0.6-2.6)nmol/L, testosterone
0.7(reference range 0.1-3.1)nmol/L, dehydroepiandrosterone sulfate
<0.15(reference range 0.80-5.6)mg/L, androstenedione <0.3 (reference range 0.6
3.1) MUg/L, luteinizing hormone 6.6(reference range 0.6-1.7)U/L, follicle
stimulating hormone 1.8 (reference range 0.5-3.7)U/L, estradiol 37.66(reference
range 73.4-146.8)pmol/L. The patient had normal levels of serum sodium,
potassium, corticosteroid and plasma adrenocorticotropic hormone. Genomic DNA was
extracted from the leukocytes of peripheral blood of the patient and subjected to
next generation sequencing (NGS) for testing more than 200 sexual development
related genes. Sanger sequencing was used to confirm the results of NGS. Genetic
analysis revealed that the patient harbored compound heterozygous mutations of c.
1226C>G (p.Pro409Arg, P409R) and c. 707T>G (p.Val236Gly, V236G) in CYP17A1 gene
derived from paternal and maternal allele. V236G was a novel mutation predicted
to be pathogenic. The infant was diagnosed as isolated 17, 20-lyase deficiency
combined with clinical and molecular characteristics of CYP17A1 gene. CONCLUSION:
We have identified the compound heterozygous mutations of P409R and V236G in the
CYP17A1 gene in one infant with isolated 17, 20-lyase deficiency. He presented
with 46, XY gonadal dysgenesis, normal blood pressure and elevated concentration
of progesterone and 17-hydroxyprogesterone.
PMID- 27510878
TI - [Vein of Galen malformations in two neonates].
PMID- 27510879
TI - [Zika virus: research progress, diagnosis and control].
PMID- 27510881
TI - [The effect of human cytomegalovirus microRNA on virus latent infection].
PMID- 27510880
TI - [Immunotherapy for Epstein-Barr virus-associated disorders].
PMID- 27510882
TI - [Therapeutic progress in spinal muscular atrophy].
PMID- 27510883
TI - [Sleep-disordered breathing in the Pierre-Robin syndrome children].
PMID- 27510884
TI - In vitro comparison of intracranial stent visibility using various concentrations
of gadolinium contrast agent under 1.5 T and 3 T MR angiography.
AB - BACKGROUND AND PURPOSE: MR angiography (MRA) is an increasingly used evaluation
method following intracranial stenting. However, the various artifacts created by
the stent limit this technique. The purpose of this study was to investigate the
effects of various concentrations of gadolinium contrast agent on the visibility
and signal characteristics of two stents using the a contrast enhanced MRA
technique. MATERIAL AND METHOD: Two intracranial stents (Enterprise and
Helistent) were placed in polyvinyl chloride tubes as vascular phantoms. They
were filled with six different doses of gadolinium contrast agent (1.0, 2.0, 4.0,
6.0, 8.0, and 10.0 mmol/L dimeglumine gadopentetate, respectively) and imaged
using 3 T and 1.5 T MR systems. Relative in-stent signal (RIS) was calculated and
artificial luminal narrowing (ALN) was obtained using pixel by pixel analysis.
RESULT: The Enterprise stent, performed in both 1.5 T and 3 T MR systems, showed
mean RIS values much less than those for the Helistent for all different doses of
gadolinium solution. Increased gadolinium concentration resulted in a gradual
reduction in RIS values in the Enterprise group. Also, ALN in the Enterprise
group showed no or little change with various gadolinium doses. CONCLUSIONS: The
Enterprise stent demonstrated good luminal visibility regardless of gadolinium
concentration. The relative in-stent signals were more predictable in the
Enterprise stent with various doses of gadolinium. Therefore, the Enterprise
stent has been shown to provide better in-stent visibility compared with the
Helistent using various gadolinium doses.
PMID- 27510885
TI - Fistulous-type vein of Galen malformation phantom model for endovascular training
and research.
AB - INTRODUCTION: Vein of Galen malformation (VGM), a high-flow intracranial
arteriovenous shunt, is among the most severe neurovascular diseases in
childhood. In many cases untreated children die or survive only severely
disabled. Endovascular embolization is the preferred treatment. OBJECTIVE: To
develop a simple fistulous-type VGM phantom model for teaching and training of
different endovascular treatment methods and to investigate new treatment options
and devices. METHODS: An experimental in vitro pulsatile phantom model was
developed imitating a high-flow fistulous-type VGM, which is typical, especially
in the neonatal phase. Pressure measurements at different arterial sites were
performed before and after closure of the VGM. Closure of the VGM was achieved by
coiling using a combined microcatheter-based transvenous and transarterial
approach called 'kissing microcatheter technique'. RESULTS: The behaviour of the
phantom model in vitro under fluoroscopy and under angiographic runs was
extremely similar to that in in vivo conditions in children. The results showed
that intra-arterial pressures changed and increased statistically significantly
at all measurement sites after embolization, as in human arteriovenous
malformation. We also demonstrated different and complementary visualizations of
hemodynamics and angioarchitecture by antegrade and retrograde microcatheter
injections. CONCLUSIONS: Our phantom model behaves like a typical fistulous-type
VGM and can be used in vitro for teaching and training and for further research.
It offers a new and better understanding of hemodynamics and angioarchitecture in
the endovascular management of VGM.
PMID- 27510886
TI - The law and medicine - One family's view.
PMID- 27510887
TI - Res ipsa loquitor: No sui generis application to aesthetic surgery.
AB - The doctrine of res ipsa loquitor can allow a plaintiff to raise an inference of
negligence which a defendant is then compelled to refute. However, the doctrine
has rarely been applied in clinical negligence contexts because courts have been
reluctant to require doctors to refute an inference of responsibility for
pathophysiological outcomes. But does that imperative apply equally to aesthetic
surgery? A recent case shows that it does.
PMID- 27510888
TI - When Your N >1: Drawing Meaningful Conclusions from Registry Studies.
PMID- 27510889
TI - Etoposide damages female germ cells in the developing ovary.
AB - BACKGROUND: As with many anti-cancer drugs, the topoisomerase II inhibitor
etoposide is considered safe for administration to women in the second and third
trimesters of pregnancy, but assessment of effects on the developing fetus have
been limited. The purpose of this research was to examine the effect of etoposide
on germ cells in the developing ovary. Mouse ovary tissue culture was used as the
experimental model, thus allowing us to examine effects of etoposide on all
stages of germ cell development in the same way, in vitro. RESULTS: Fetal ovaries
from embryonic day 13.5 CD1 mice or neonatal ovaries from postnatal day 0 CD1
mice were cultured with 50-150 ng ml(-1) or 50-200 ng ml(-1) etoposide
respectively, concentrations that are low relative to that in patient serum. When
fetal ovaries were treated prior to follicle formation, etoposide resulted in
dose-dependent damage, with 150 ng ml(-1) inducing a near-complete absence of
healthy follicles. In contrast, treatment of neonatal ovaries, after follicle
formation, had no effect on follicle numbers and only a minor effect on follicle
health, even at 200 ng ml(-1). The sensitivity of female germ cells to etoposide
coincided with topoisomerase IIalpha expression: in the developing ovary of both
mouse and human, topoisomerase IIalpha was expressed in germ cells only prior to
follicle formation. CONCLUSIONS: Exposure of pre-follicular ovaries, in which
topoisomerase IIalpha expression was germ cell-specific, resulted in a near
complete elimination of germ cells prior to follicle formation, with the
remaining germ cells going on to form unhealthy follicles by the end of culture.
In contrast, exposure to follicle-enclosed oocytes, which no longer expressed
topoisomerase IIalpha in the germ cells, had no effect on total follicle numbers
or health, the only effect seen specific to transitional follicles. Results
indicate the potential for adverse effects on fetal ovarian development if
etoposide is administered to pregnant women when germ cells are not yet enclosed
within ovarian follicles, a process that starts at approximately 17 weeks
gestation and is only complete towards the end of pregnancy.
PMID- 27510890
TI - Predicting the outcomes of using longer-acting prophylactic factor VIII to treat
people with severe hemophilia A: a hypothetical decision analysis.
AB - Essentials No randomized trials have compared long-acting factor VIII (FVIII)
with currently used products. A comparison was undertaken using a decision model
to predict FVIII use and number of bleeds. In the base case, longer acting FVIII
reduced factor use by 17% while resulting in similar bleeds. The value of longer
acting FVIII will be largely determined by existing regimens and unit price.
Click to hear Prof. Makris's presentation on new treatments in hemophilia
SUMMARY: Background Recently, factor VIII (FVIII) products with longer half
lives, such as recombinant FVIII Fc fusion protein (rFVIIIFc), have become
available. Use of longer-acting FVIII products will largely depend on
effectiveness and cost; no direct evaluations have compared these parameters
between conventional and longer-acting FVIII therapies. Objectives To present a
hypothetical decision analysis, combining evidence from multiple sources to
estimate bleeding frequency, resource use and cost of longer-acting prophylactic
products, such as rFVIIIFc, vs. conventional recombinant FVIII (rFVIII).
Patients/Methods The decision model used published pharmacokinetic parameters,
bleeding frequency vs. time information below a 1-IU dL-1 FVIII trough level, and
adherence. Prophylactic treatment scenarios were modelled for a hypothetical
patient with severe hemophilia A (<1 IU/dL) receiving rFVIIIFc or rFVIII. Results
Infusing twice weekly with rFVIIIFc 42.7 IU kg-1 per dose required less clotting
factor than infusing every 56 h with rFVIII 33.75 IU kg-1 per dose; annual
bleeding rates were similar. Base case analysis suggested that total FVIII costs
were equated when rFVIIIFc cost 1.18 times more per IU than rFVIII, assuming
similar adherence. Other modelled scenarios produced similar results, although
differences in FVIII consumption were particularly sensitive to assumptions
regarding frequency and dose of the rFVIII and rFVIIIFc regimens. For example,
decreasing rFVIII from 33.75 IU kg-1 to 30 IU kg-1 per dose decreased the price
factor to 1.05. Conclusions Longer-acting FVIII products may reduce FVIII
consumption and infusion frequency without compromising hemostatic effect; this
should be considered along with other factors (e.g. adherence and underlying
FVIII regimen) when evaluating a suitable price for these agents.
PMID- 27510891
TI - A New Advanced Backcross Tomato Population Enables High Resolution Leaf QTL
Mapping and Gene Identification.
AB - Quantitative Trait Loci (QTL) mapping is a powerful technique for dissecting the
genetic basis of traits and species differences. Established tomato mapping
populations between domesticated tomato (Solanum lycopersicum) and its more
distant interfertile relatives typically follow a near isogenic line (NIL)
design, such as the S. pennellii Introgression Line (IL) population, with a
single wild introgression per line in an otherwise domesticated genetic
background. Here, we report on a new advanced backcross QTL mapping resource for
tomato, derived from a cross between the M82 tomato cultivar and S. pennellii
This so-called Backcrossed Inbred Line (BIL) population is comprised of a mix of
BC2 and BC3 lines, with domesticated tomato as the recurrent parent. The BIL
population is complementary to the existing S. pennellii IL population, with
which it shares parents. Using the BILs, we mapped traits for leaf complexity,
leaflet shape, and flowering time. We demonstrate the utility of the BILs for
fine-mapping QTL, particularly QTL initially mapped in the ILs, by fine-mapping
several QTL to single or few candidate genes. Moreover, we confirm the value of a
backcrossed population with multiple introgressions per line, such as the BILs,
for epistatic QTL mapping. Our work was further enabled by the development of our
own statistical inference and visualization tools, namely a heterogeneous hidden
Markov model for genotyping the lines, and by using state-of-the-art sparse
regression techniques for QTL mapping.
PMID- 27510892
TI - Correlation between vitiligo occurrence and clinical benefit in advanced melanoma
patients treated with nivolumab: A multi-institutional retrospective study.
AB - Vitiligo is occasionally seen in melanoma patients. Although several studies
indicate a correlation between vitiligo occurrence and clinical response in
melanoma patients receiving immunotherapy, most studies have included
heterogeneous patient and treatment settings. The aim of this study is to
investigate the correlation between the occurrence of vitiligo and clinical
benefit of nivolumab treatment in advanced melanoma patients. We retrospectively
reviewed unresectable stage III or IV melanoma patients treated with nivolumab.
Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo
during treatment. The time from the start of nivolumab treatment to occurrence of
vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo,
two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial
response. The objective response rate was significantly higher in patients with
vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]; P =
0.027). The mean time to vitiligo occurrence in patients achieving an objective
response was significantly less than that in patients who showed no response (3.1
vs 6.8 months, P = 0.004). Vitiligo occurrence was significantly associated with
prolonged progression-free and overall survival (hazard ratio, 0.24 and 0.16; 95%
confidence interval, 0.11-0.55 and 0.03-0.79; P = 0.005, and 0.047,
respectively). At the 20-week landmark analysis, however, vitiligo was not
associated with a statistically significant overall survival benefit (P = 0.28).
The occurrence of vitiligo during nivolumab treatment may be correlated with
favorable clinical outcome.
PMID- 27510893
TI - Analysis of the influence of 111In on 90Y-bremsstrahlung SPECT based on Monte
Carlo simulation.
AB - OBJECTIVE: 90Y-ibritumomab tiuxetan (Zevalin) which is used for the treatment of
malignant lymphomas can be used for SPECT imaging based on bremsstrahlung from
90Y beta particles. However, gamma rays emitted by 111In, which is administered
to evaluate the indication for the treatment, contaminate the 90Y bremsstrahlung
images. Our objective is to investigate the influence of 111In on the 90Y SPECT
images using Monte Carlo simulation. METHODS: We used an in-house developed
simulation code for the Monte Carlo simulation of electrons and photons (MCEP).
Two hot spheres with diameters of 40 mm were put in an elliptical phantom. Both
spheres ("sphere 1" and "sphere 2") were filled with 90Y and 111In mixed
solutions. The activities of 90Y in sphere 1 and sphere 2 were 241 and 394
kBq/mL, respectively, and the ones of 111In were 8.14 and 13.3 kBq/mL,
respectively. The background activity of 90Y was 38.6 kBq/mL, whereas that of
111In was 1.30 kBq/mL; moreover, the acquisition time was 30 min. Two energy
windows were used: one is 90-190 keV included the 111In photopeak; the other is
90-160 keV. To evaluate the quality of the SPECT images, the contrast recovery
coefficient (CRC) and the constant noise ratio (CNR) of the SPECT images were
derived. RESULTS: For the energy window between 90 and 160 keV, the 111In count
was 74 % of the total. In that case, the CRC values were 30.1 and 30.7 % for
"sphere 1" and "sphere 2", respectively, whereas the CNR values were 6.8 and
12.1, respectively. For the energy window between 90 and 190 keV, the 111In count
reached 85 % of the total count. The CRC and CNR values were 38.6 and 40.0 % and
10.6 and 19.4, respectively. CONCLUSIONS: Our simulation study revealed that the
cross talk between 111In and 90Y in SPECT imaging is rather serious. Even for the
energy window excluding the 111In photopeak, the count ratio of 90Y was less than
30 % of the total. However, the influence of 111In on 90Y-SPECT imaging cannot be
ignored, and the count ratio because of 111In is important to estimate the
density of 90Y.
PMID- 27510894
TI - An Unusual Case of White Piedra Due to Trichosporon inkin Mimicking
Trichobacteriosis.
AB - White piedra is a superficial mycosis characterized by soft, white-to-tan,
irregular nodules attached to the hair shafts. A 36-year-old man presented with
small lumps in his pubic hair, without any other symptoms. The clinical features
were suggestive of trichobacteriosis. Pathology analysis of the infected hair
revealed that the concretions surrounding the hair shaft were full of fungal
elements, parts of which had invaded into the cuticle. Culture on Sabouraud
dextrose agar grew creamy, yellow-white colonies identified as Trichosporon inkin
by the sequence of the nuclear ribosomal intergenic spacer region. The condition
was treated by shaving the pubic hair and administering antifungal therapy (oral
itraconazole and topical ketoconazole).
PMID- 27510896
TI - Transient spontaneous remission in congenital MLL-AF10 rearranged acute myeloid
leukemia presenting with cardiorespiratory failure and meconium ileus.
AB - BACKGROUND: Neonatal leukemia is a rare disease with an estimated prevalence of
about one to five in a million neonates. The majority being acute myeloid
leukemia (AML), neonatal leukemia can present with a variety of symptoms
including hyperleucocytosis, cytopenia, hepatosplenomegaly, and skin infiltrates.
Chromosomal rearrangements including mixed lineage leukemia (MLL) translocations
are common in neonatal AML. CASE PRESENTATION: A female neonate born at 34 weeks
gestation presented with cardiorespiratory failure, hepatosplenomegaly,
pancytopenia, and coagulopathy. She required intensive care treatment including
mechanical ventilation, high-dose catecholamine therapy, and multiple
transfusions. Small intestinal biopsy obtained during laparotomy for meconium
ileus revealed an infiltrate by an undifferentiated monoblastic, MLL-rearranged
leukemia. No other manifestations of leukemia could be detected. After
spontaneous clinical remission, lasting 5 months without any specific treatment,
the patient presented with leukemia cutis and full-blown monoblastic leukemia.
MLL-AF10-rearranged AML could be re-diagnosed and successfully treated with
chemotherapy and hematopoietic stem cell transplantation. CONCLUSIONS: Our
patient exhibited a unique manifestation of neonatal MLL-AF10 rearranged AML with
cardiorespiratory failure and intestinal infiltration. It highlights the
importance of leukemia in the differential diagnosis of neonatal distress,
congenital hematological abnormalities, and skin lesions.
PMID- 27510897
TI - Early origins of asthma (and allergy).
AB - Asthma is the most common chronic disease starting in childhood and persisting
into adulthood in many cases. During childhood, different forms of asthma and
wheezing disorders exist that can be discriminated by the mechanisms they are
caused by. Specific genetic constellations and exposure against environmental
factors during early childhood and in utero play a decisive role in the early
development of the disease. Epigenetic mechanisms which are master regulators of
gene transcription and thus govern the accessibility and use of genome
information, have recently been identified as a "third power" determining many
features in the early development of asthma and allergy.
PMID- 27510895
TI - Normal radial migration and lamination are maintained in dyslexia-susceptibility
candidate gene homolog Kiaa0319 knockout mice.
AB - Developmental dyslexia is a common disorder with a strong genetic component, but
the underlying molecular mechanisms are still unknown. Several candidate dyslexia
susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified
in humans. RNA interference experiments targeting these genes in rat embryos have
shown impairments in neuronal migration, suggesting that defects in radial
cortical migration could be involved in the disease mechanism of dyslexia. Here
we present the first characterisation of a Kiaa0319 knockout mouse line. Animals
lacking KIAA0319 protein do not show anatomical abnormalities in any of the
layered structures of the brain. Neurogenesis and radial migration of cortical
projection neurons are not altered, and the intrinsic electrophysiological
properties of Kiaa0319-deficient neurons do not differ from those of wild-type
neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not
affect final neuronal position. However, knockout animals show subtle differences
suggesting possible alterations in anxiety-related behaviour and in sensorimotor
gating. Our results do not reveal a migration disorder in the mouse model, adding
to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in
utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes
do not play an evident role in neuronal migration. However, KIAA0319 protein
expression seems to be restricted to the brain, not only in early developmental
stages but also in adult mice, indicative of a role of this protein in brain
function. The constitutive and conditional knockout lines reported here will be
useful tools for further functional analyses of Kiaa0319.
PMID- 27510898
TI - Rita Redberg: an unwavering campaigner against the harms of too much medicine.
PMID- 27510899
TI - A physician-scientist's wish list for the 2016 U.S. presidential candidates.
PMID- 27510900
TI - Erratum for the Research Article: "Maternal HIV infection influences the
microbiome of HIV-uninfected infants" by J. M. Bender, F. Li, S. Martelly, E.
Byrt, V. Rouzier, M. Leo, N. Tobin, P. S. Pannaraj, H. Adisetiyo, A. Rollie, C.
Santiskulvong, S. Wang, C. Autran, L. Bode, D. Fitzgerald, L. Kuhn, G. M.
Aldrovandi.
PMID- 27510901
TI - Hematopoietic stem cell transplantation in immunocompetent hosts without
radiation or chemotherapy.
AB - Hematopoietic stem cell (HSC) transplantation can cure diverse diseases of the
blood system, including hematologic malignancies, anemias, and autoimmune
disorders. However, patients must undergo toxic conditioning regimens that use
chemotherapy and/or radiation to eliminate host HSCs and enable donor HSC
engraftment. Previous studies have shown that anti-c-Kit monoclonal antibodies
deplete HSCs from bone marrow niches, allowing donor HSC engraftment in
immunodeficient mice. We show that host HSC clearance is dependent on Fc-mediated
antibody effector functions, and enhancing effector activity through blockade of
CD47, a myeloid-specific immune checkpoint, extends anti-c-Kit conditioning to
fully immunocompetent mice. The combined treatment leads to elimination of >99%
of host HSCs and robust multilineage blood reconstitution after HSC
transplantation. This targeted conditioning regimen that uses only biologic
agents has the potential to transform the practice of HSC transplantation and
enable its use in a wider spectrum of patients.
PMID- 27510902
TI - Insights into neuroepigenetics through human histone deacetylase PET imaging.
AB - Epigenetic dysfunction is implicated in many neurological and psychiatric
diseases, including Alzheimer's disease and schizophrenia. Consequently, histone
deacetylases (HDACs) are being aggressively pursued as therapeutic targets.
However, a fundamental knowledge gap exists regarding the expression and
distribution of HDACs in healthy individuals for comparison to disease states.
Here, we report the first-in-human evaluation of neuroepigenetic regulation in
vivo. Using positron emission tomography with [(11)C]Martinostat, an imaging
probe selective for class I HDACs (isoforms 1, 2, and 3), we found that HDAC
expression is higher in cortical gray matter than in white matter, with conserved
regional distribution patterns within and between healthy individuals. Among gray
matter regions, HDAC expression was lowest in the hippocampus and amygdala.
Through biochemical profiling of postmortem human brain tissue, we confirmed that
[(11)C]Martinostat selectively binds HDAC isoforms 1, 2, and 3, the HDAC subtypes
most implicated in regulating neuroplasticity and cognitive function. In human
stem cell-derived neural progenitor cells, pharmacologic-level doses of
Martinostat induced changes in genes closely associated with synaptic plasticity,
including BDNF (brain-derived neurotrophic factor) and SYP (synaptophysin), as
well as genes implicated in neurodegeneration, including GRN (progranulin), at
the transcript level, in concert with increased acetylation at both histone H3
lysine 9 and histone H4 lysine 12. This study quantifies HDAC expression in the
living human brain and provides the foundation for gaining unprecedented in vivo
epigenetic information in health and disease.
PMID- 27510904
TI - Vacuolar H+-ATPase in the nuclear membranes regulates nucleo-cytosolic proton
gradients.
AB - The regulation of the luminal pH of each organelle is crucial for its function
and must be controlled tightly. Nevertheless, it has been assumed that the
nuclear pH is regulated by the cytoplasmic proton transporters via the diffusion
of H+ across the nuclear pores because of their large diameter. However, it has
been demonstrated that ion gradients exist between cytosol and nucleus,
suggesting that the permeability of ions across the nuclear pores is restricted.
Vacuolar H+-ATPase (V-H+-ATPase) is responsible for the creation and maintenance
of trans-membrane electrochemical gradient. We hypothesize that V-H+-ATPase
located in the nuclear membranes functions as the primary mechanism to regulate
nuclear pH and generate H+ gradients across the nuclear envelope. We studied the
subcellular heterogeneity of H+ concentration in the nucleus and cytosol using
ratio imaging microscopy and SNARF-1, a pH indicator, in prostate cells. Our
results indicate that there are proton gradients across the nuclear membranes
that are generated by V-H+-ATPase located in the outer and inner nuclear
membranes. We demonstrated that these gradients are mostly dissipated by
inhibiting V-H+-ATPase. Immunoblots and V-H+-ATPase activity corroborated the
existence of V-H+-ATPase in the nuclear membranes. This study demonstrates that V
H+-ATPase is functionally expressed in nuclear membranes and is responsible for
nuclear H+ gradients that may promote not only the coupled transport of
substrates, but also most electrochemically driven events across the nuclear
membranes. This study represents a paradigm shift that the nucleus can regulate
its own pH microenvironment, providing new insights into nuclear ion homeostasis
and signaling.
PMID- 27510905
TI - The ubiquitin proteasome system in atrophying skeletal muscle: roles and
regulation.
AB - Muscle atrophy complicates many diseases as well as aging, and its presence
predicts both decreased quality of life and survival. Much work has been
conducted to define the molecular mechanisms involved in maintaining protein
homeostasis in muscle. To date, the ubiquitin proteasome system (UPS) has been
shown to play an important role in mediating muscle wasting. In this review, we
have collated the enzymes in the UPS whose roles in muscle wasting have been
confirmed through loss-of-function studies. We have integrated information on
their mechanisms of action to create a model of how they work together to produce
muscle atrophy. These enzymes are involved in promoting myofibrillar disassembly
and degradation, activation of autophagy, inhibition of myogenesis as well as in
modulating the signaling pathways that control these processes. Many anabolic and
catabolic signaling pathways are involved in regulating these UPS genes, but none
appear to coordinately regulate a large number of these genes. A number of
catabolic signaling pathways appear to instead function by inhibition of the
insulin/IGF-I/protein kinase B anabolic pathway. This pathway is a critical
determinant of muscle mass, since it can suppress key ubiquitin ligases and
autophagy, activate protein synthesis, and promote myogenesis through its
downstream mediators such as forkhead box O, mammalian target of rapamycin, and
GSK3beta, respectively. Although much progress has been made, a more complete
inventory of the UPS genes involved in mediating muscle atrophy, their mechanisms
of action, and their regulation will be useful for identifying novel therapeutic
approaches to this important clinical problem.
PMID- 27510903
TI - Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to
pulmonary fibrosis-emphysema.
AB - Chronic obstructive pulmonary disease and pulmonary fibrosis have been
hypothesized to represent premature aging phenotypes. At times, they cluster in
families, but the genetic basis is not understood. We identified rare, frameshift
mutations in the gene for nuclear assembly factor 1, NAF1, a box H/ACA RNA
biogenesis factor, in pulmonary fibrosis-emphysema patients. The mutations
segregated with short telomere length, low telomerase RNA levels, and
extrapulmonary manifestations including myelodysplastic syndrome and liver
disease. A truncated NAF1 was detected in cells derived from patients, and, in
cells in which the frameshift mutation was introduced by genome editing,
telomerase RNA levels were reduced. The mutant NAF1 lacked a conserved carboxyl
terminal motif, which we show is required for nuclear localization. To understand
the disease mechanism, we used CRISPR (clustered regularly interspaced short
palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) to generate
Naf1(+/-) mice and found that they had half the levels of telomerase RNA. Other
box H/ACA RNA levels were also decreased, but rRNA pseudouridylation, which is
guided by snoRNAs, was intact. Moreover, first-generation Naf1(+/-) mice showed
no evidence of ribosomal pathology. Our data indicate that disease in NAF1
mutation carriers is telomere-mediated; they show that NAF1 haploinsufficiency
selectively disturbs telomere length homeostasis by decreasing the levels of
telomerase RNA while sparing rRNA pseudouridylation.
PMID- 27510906
TI - Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and
phosphorylation in proximal tubule cells.
AB - Binding of angiotensin II (ANG II) to the AT1 receptor (AT1R) in the proximal
tubule stimulates Na+/H+ exchanger isoform 3 (NHE3) activity through multiple
signaling pathways. However, the effects of ANG II/AT1R-induced inihibitory G
protein (Gi) activation and subsequent decrease in cAMP accumulation on NHE3
regulation are not well established. We therefore tested the hypothesis that ANG
II reduces cAMP/PKA-mediated phosphorylation of NHE3 on serine 552 and, in doing
so, stimulates NHE3 activity. Under basal conditions, ANG II stimulated NHE3
activity but did not affect PKA-mediated NHE3 phosphorylation at serine 552 in
opossum kidney (OKP) cells. However, in the presence of the cAMP-elevating agent
forskolin (FSK), ANG II blocked FSK-induced NHE3 inhibition, reduced
intracellular cAMP concentrations, lowered PKA activity, and prevented the FSK
mediated increase in NHE3 serine 552 phosphorylation. All effects of ANG II were
blocked by pretreating OKP cells with the AT1R antagonist losartan, highlighting
the contribution of the AT1R/Gi pathway in ANG II-mediated NHE3 upregulation
under cAMP-elevating conditions. Accordingly, Gi inhibition by pertussis toxin
treatment decreased NHE3 activity both in vitro and in vivo and, more
importantly, prevented the stimulatory effect of ANG II on NHE3 activity in rat
proximal tubules. Collectively, our results suggest that ANG II counteracts the
effects of cAMP/PKA on NHE3 phosphorylation and inhibition by activating the
AT1R/Gi pathway. Moreover, these findings support the notion that NHE3
dephosphorylation at serine 552 may represent a key event in the regulation of
renal proximal tubule sodium handling by ANG II in the presence of natriuretic
hormones that promote cAMP accumulation and transporter phosphorylation.
PMID- 27510907
TI - NK Cell Regulatory Property is Involved in the Protective Role of MSC-Derived
Extracellular Vesicles in Renal Ischemic Reperfusion Injury.
AB - Immunomodulation has been regarded as an important therapeutic aspect of
mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in renal
ischemic reperfusion injury (IRI), and the specific mechanism still unclear.
Here, we attempt to test the function of human MSC-EVs on renal IRI by targeting
the natural killer (NK) cells and to investigate the possible mechanism. Data
indicated that EVs decreased NK cells in spleen and ischemic kidney. Both the EVs
and antibody-dependent depletion of NK cells displayed a protective role in IRI
rats. Moreover, the splenectomy model was established to evaluate the role of
spleen in this process. It showed that the NK cell regulatory ability and renal
protective effects by EVs still exist without spleen, which is unlike MSC
properties published previously. Further, the down-regulation of chemokines in
injured kidney and the delivery of RNAs through EVs in vitro were also observed.
Through the microRNA array test, various inflammation-related microRNAs highly
expressed in MSC-EVs compared with fibroblast EVs were tested. Thus, these
results indicated that MSC-EVs could ameliorate renal ischemic reperfusion injury
by decreasing NK cells and the spleen is not necessary in this process. The
regulation of chemokines in injured kidney was the other factor, and the transfer
of various microRNAs in the MSC-EVs may be involved. This provides direction for
future clinical applications.
PMID- 27510908
TI - Visual analytics of geo-social interaction patterns for epidemic control.
AB - BACKGROUND: Human interaction and population mobility determine the spatio
temporal course of the spread of an airborne disease. This research views such
spreads as geo-social interaction problems, because population mobility connects
different groups of people over geographical locations via which the viruses
transmit. Previous research argued that geo-social interaction patterns
identified from population movement data can provide great potential in designing
effective pandemic mitigation. However, little work has been done to examine the
effectiveness of designing control strategies taking into account geo-social
interaction patterns. METHODS: To address this gap, this research proposes a new
framework for effective disease control; specifically this framework proposes
that disease control strategies should start from identifying geo-social
interaction patterns, designing effective control measures accordingly, and
evaluating the efficacy of different control measures. This framework is used to
structure design of a new visual analytic tool that consists of three components:
a reorderable matrix for geo-social mixing patterns, agent-based epidemic models,
and combined visualization methods. RESULTS: With real world human interaction
data in a French primary school as a proof of concept, this research compares the
efficacy of vaccination strategies between the spatial-social interaction
patterns and the whole areas. The simulation results show that locally targeted
vaccination has the potential to keep infection to a small number and prevent
spread to other regions. At some small probability, the local control strategies
will fail; in these cases other control strategies will be needed. This research
further explores the impact of varying spatial-social scales on the success of
local vaccination strategies. The results show that a proper spatial-social scale
can help achieve the best control efficacy with a limited number of vaccines.
CONCLUSIONS: The case study shows how GS-EpiViz does support the design and
testing of advanced control scenarios in airborne disease (e.g., influenza). The
geo-social patterns identified through exploring human interaction data can help
target critical individuals, locations, and clusters of locations for disease
control purposes. The varying spatial-social scales can help geographically and
socially prioritize limited resources (e.g., vaccines).
PMID- 27510909
TI - HIV Testing Services in Africa: Are They Sustainable?
AB - HIV testing services (HTS) are an essential component of a national response to
the HIV epidemic, and in lower and middle income countries, at least 150 million
persons are tested annually. HIV testing is necessary to identify persons in need
of antiretroviral treatment, which has been documented to be highly effective not
only for treatment but also for prevention of HIV transmission to both adults and
children. An assessment of the recent literature on sustainability of health and
HIV services suggests that organizational performance, flexibility, and
integration with other health interventions contribute to sustainability of HIV
services and programs. This article describes the experiences of two HIV testing
service providers in Uganda and Zambia as well as the track record of services to
prevent mother-to-child HIV transmission to illustrate the factors of
performance, flexibility, adaptability, and integration which are key to the
sustainability of HIV testing services.
PMID- 27510910
TI - MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in
mice.
AB - AIMS/HYPOTHESIS: Diabetic cardiomyopathy (DCM) is associated with suppressed
autophagy and augmented apoptosis in the heart although the interplay between the
two remains elusive. The ability of mammalian sterile 20-like kinase 1 to
regulate both autophagy and apoptosis prompted us to investigate it as a possible
candidate in the progression of DCM. METHODS: Wild-type, Mst1 (also known as
Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to
induce experimental diabetes. In addition, cultured neonatal mouse cardiomyocytes
were subjected to simulated diabetes to probe mechanisms. RESULTS: Mst1 knockout
alleviated while Mst1 overexpression aggravated cardiac dysfunction in diabetes.
Diabetic Mst1 transgenic mice exhibited decreased LC3 expression and enhanced
protein aggregation. In contrast, typical autophagosomes were observed in
diabetic Mst1-knockout mice with increased LC3 expression and reduced protein
aggregation. Mst1 downregulation promoted autophagic flux as demonstrated by
increased LC3-II and decreased p62 expression in the presence of bafilomycin A1.
Furthermore, Mst1 overexpression increased, while Mst1 knockout decreased,
cardiomyocyte apoptosis both in vivo and in vitro. Co-immunoprecipitation assays
showed that Mst1 overexpression promoted Beclin1 binding to B cell lymphoma 2
(Bcl-2) and induced dissociation of Bcl-2 from Bax in diabetic mice. Conversely,
Mst1 knockout disrupted the Beclin1-Bcl-2 complex and enhanced the interaction
between Bcl-2 and Bax. CONCLUSIONS/INTERPRETATION: Mst1 knockout restores
autophagy and protects against apoptosis in cardiomyocytes, en route to the
rescue against DCM.
PMID- 27510911
TI - Maternal gestational diabetes and childhood obesity at age 9-11: results of a
multinational study.
AB - AIMS/HYPOTHESIS: The aim of this study was to examine the association between
maternal gestational diabetes mellitus (GDM) and childhood obesity at age 9-11
years in 12 countries around the world. METHODS: A multinational cross-sectional
study of 4740 children aged 9-11 years was conducted. Maternal GDM was diagnosed
according to the ADA or WHO criteria. Height and waist circumference were
measured using standardised methods. Weight and body fat were measured using a
portable Tanita SC-240 Body Composition Analyzer. Multilevel modelling was used
to account for the nested nature of the data. RESULTS: The prevalence of reported
maternal GDM was 4.3%. The overall prevalence of childhood obesity, central
obesity and high body fat were 12.3%, 9.9% and 8.1%, respectively. The
multivariable-adjusted (maternal age at delivery, education, infant feeding mode,
gestational age, number of younger siblings, child unhealthy diet pattern scores,
moderate-to-vigorous physical activity, sleeping time, sedentary time, sex and
birthweight) odds ratios among children of GDM mothers compared with children of
non-GDM mothers were 1.53 (95% CI 1.03, 2.27) for obesity, 1.73 (95% CI 1.14,
2.62) for central obesity and 1.42 (95% CI 0.90, 2.26) for high body fat. The
positive association was still statistically significant for central obesity
after additional adjustment for current maternal BMI but was no longer
significant for obesity and high body fat. CONCLUSIONS/INTERPRETATION: Maternal
GDM was associated with increased odds of childhood obesity at 9-11 years old but
this association was not fully independent of maternal BMI.
PMID- 27510912
TI - Transfer characteristics of subretinal visual implants: corneally recorded
implant responses.
AB - PURPOSE: The subretinal Alpha IMS visual implant is a CE-approved medical device
for restoration of visual functions in blind patients with end-stage outer retina
degeneration. We present a method to test the function of the implant objectively
in vivo using standard electroretinographic equipment and to assess the devices'
parameter range for an optimal perception. METHODS: Subretinal implant Alpha IMS
(Retina Implant AG, Reutlingen, Germany) consists of 1500 photodiode-amplifier
electrode units and is implanted surgically into the subretinal space in blind
retinitis pigmentosa patients. The voltages that regulate the amplifiers'
sensitivity (V gl) and gain (V bias), related to the perception of contrast and
brightness, respectively, are adjusted manually on a handheld power supply
device. Corneally recorded implant responses (CRIR) to full-field illumination
with long duration flashes in various implant settings for brightness gain (V
bias) and amplifiers' sensitivity (V gl) are measured using electroretinographic
setup with a Ganzfeld bowl in a protocol of increasing stimulus luminances up to
1000 cd/m2. RESULTS: CRIRs are a meaningful tool for assessing the transfer
characteristic curves of the electronic implant in vivo monitoring the implants'
voltage output as a function of log luminance in a sigmoidal shape. Changing the
amplifiers' sensitivity (V gl) shifts the curve left or right along the log
luminance axis. Adjustment of the gain (V bias) changes the maximal output.
Contrast perception is only possible within the luminance range of the increasing
slope of the function. CONCLUSIONS: The technical function of subretinal visual
implants can be measured objectively using a standard electroretinographic setup.
CRIRs help the patient to optimise the perception by adjusting the gain and
luminance range of the device and are a useful tool for clinicians to objectively
assess the function of subretinal visual implants in vivo.
PMID- 27510913
TI - 3D nanostructured inkjet printed graphene via UV-pulsed laser irradiation enables
paper-based electronics and electrochemical devices.
AB - Emerging research on printed and flexible graphene-based electronics is beginning
to show tremendous promise for a wide variety of fields including wearable
sensors and thin film transistors. However, post-print annealing/reduction
processes that are necessary to increase the electrical conductivity of the
printed graphene degrade sensitive substrates (e.g., paper) and are whole
substrate processes that are unable to selectively anneal/reduce only the printed
graphene-leaving sensitive device components exposed to damaging heat or
chemicals. Herein a pulsed laser process is introduced that can selectively
irradiate inkjet printed reduced graphene oxide (RGO) and subsequently improve
the electrical conductivity (Rsheet~0.7 kOmega?(-1)) of printed graphene above
previously published reports. Furthermore, the laser process is capable of
developing 3D petal-like graphene nanostructures from 2D planar printed graphene.
These visible morphological changes display favorable electrochemical sensing
characteristics-ferricyanide cyclic voltammetry with a redox peak separation
(DeltaEp) ~ 0.7 V as well as hydrogen peroxide (H2O2) amperometry with a
sensitivity of 3.32 MUA mM(-1) and a response time of <5 s. Thus this work paves
the way for not only paper-based electronics with graphene circuits, it enables
the creation of low-cost and disposable graphene-based electrochemical electrodes
for myriad applications including sensors, biosensors, fuel cells, and
theranostic devices.
PMID- 27510914
TI - RIFM fragrance ingredient safety assessment, benzyl butyrate, CAS Registry Number
103-37-7.
AB - The use of this material under current use conditions is supported by the
existing information. This material was evaluated for genotoxicity, repeated dose
toxicity, developmental and reproductive toxicity, local respiratory toxicity,
phototoxicity/photoallergenicity, skin sensitization, as well as environmental
safety. Data from the suitable read across analog benzyl acetate (CAS # 140-11-4)
show that this material is not genotoxic nor does it have skin sensitization
potential and also provided a MOE > 100 for the repeated dose, developmental and
reproductive, and local respiratory toxicity endpoints. The
phototoxicity/photoallergenicity endpoint was completed based on suitable UV
spectra. The environmental endpoint was completed as described in the RIFM
Framework.
PMID- 27510916
TI - Role of Pulse Pressure and Geometry of Primary Entry Tear in Acute Type B
Dissection Propagation.
AB - The hemodynamic and geometric factors leading to propagation of acute Type B
dissections are poorly understood. The objective is to elucidate whether
geometric and hemodynamic parameters increase the predilection for aortic
dissection propagation. A pulse duplicator set-up was used on porcine aorta with
a single entry tear. Mean pressures of 100 and 180 mmHg were used, with pulse
pressures ranging from 40 to 200 mmHg. The propagation for varying geometric
conditions (%circumference of the entry tear: 15-65%, axial length: 0.5-3.2 cm)
were tested for two flap thicknesses (1/3rd and 2/3rd of the thickness of vessel
wall, respectively). To assess the effect of pulse and mean pressure on flap
dynamics, the %true lumen (TL) cross-sectional area of the entry tear were
compared. The % circumference for propagation of thin flap (47 +/- 1%) was not
significantly different (p = 0.14) from thick flap (44 +/- 2%). On the contrary,
the axial length of propagation for thin flap (2.57 +/- 0.15 cm) was
significantly different (p < 0.05) from the thick flap (1.56 +/- 0.10 cm). TL
compression was observed during systolic phase. For a fixed geometry of entry
tear (%circumference = 39 +/- 2%; axial length = 1.43 +/- 0.13 cm), mean pressure
did not have significant (p = 0.84) effect on flap movement. Increase in pulse
pressure resulted in a significant change (p = 0.02) in %TL area (52 +/- 4%). The
energy acting on the false lumen immediately before propagation was calculated as
75 +/- 9 J/m2 and was fairly uniform across different specimens. Pulse pressure
had a significant effect on the flap movement in contrast to mean pressure.
Hence, mitigation of pulse pressure and restriction of flap movement may be
beneficial in patients with type B acute dissections.
PMID- 27510917
TI - Tissue-Engineered Tubular Heart Valves Combining a Novel Precontraction Phase
with the Self-Assembly Method.
AB - Recently, the tubular shape has been suggested as an effective geometry for
tissue-engineered heart valves, allowing easy fabrication, fast implantation, and
a minimal crimped footprint from a transcatheter delivery perspective. This
simple design is well suited for the self-assembly method, with which the only
support for the cells is the extracellular matrix they produce, allowing the
tissue to be completely free from exogenous materials during its entire
fabrication process. Tubular constructs were produced by rolling self-assembled
human fibroblast sheets on plastic mandrels. After maturation, the tubes were
transferred onto smaller diameter mandrels and allowed to contract freely. This
precontraction phase thickened the tissue and prevented further contraction,
while improving fusion between the self-assembled layers and aligning the cells
circumferentially. When mounted in a pulsed-flow bioreactor, the valves showed
good functionality with large leaflets coaptation and opening area. Although
physiological aortic flow conditions were not reached, the leaflets could
withstand a 1 Hz pulsed flow with a 300 mL/s peak flow rate and a 70 mmHg peak
transvalvular pressure. This study shows that the self-assembly method, which has
already proven its potential for the production of small diameter vascular
grafts, could also be used to achieve functional tubular heart valves.
PMID- 27510918
TI - Distribution of coniferin in freeze-fixed stem of Ginkgo biloba L. by cryo-TOF
SIMS/SEM.
AB - To clarify the role of coniferin in planta, semi-quantitative cellular
distribution of coniferin in quick-frozen Ginkgo biloba L. (ginkgo) was
visualized by cryo time-of-flight secondary ion mass spectrometry and scanning
electron microscopy (cryo-TOF-SIMS/SEM) analysis. The amount and rough
distribution of coniferin were confirmed through quantitative chromatography
measurement using serial tangential sections of the freeze-fixed ginkgo stem. The
lignification stage of the sample was estimated using microscopic observations.
Coniferin distribution visualized at the transverse and radial surfaces of freeze
fixed ginkgo stem suggested that coniferin is stored in the vacuoles, and showed
good agreement with the assimilation timing of coniferin to lignin in
differentiating xylem. Consequently, it is suggested that coniferin is stored in
the tracheid cells of differentiating xylem and is a lignin precursor.
PMID- 27510919
TI - How and why transient testing may better reveal peripheral chemoreceptor function
in humans.
PMID- 27510920
TI - Non-vitamin K antagonist oral anticoagulation usage according to age among
patients with atrial fibrillation: Temporal trends 2011-2015 in Denmark.
AB - Among atrial fibrillation (AF) patients, Danish nationwide registries (2011-2015)
were used to examine temporal trends of initiation patterns of oral
anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients
initiating vitamin K antagonists (VKA) (42%), dabigatran (29%), rivaroxaban
(13%), or apixaban (16%) were included with mean age (SD) 72.1 (11.3), 71.5
(11.0), 74.3 (11.1), and 75.3 (11.1) years, respectively. Patients aged >=85
years comprised 15%. Trend tests showed increase in patients >=85 years
initiating OAC (p < 0.0001). VKA usage decreased from 92% to 24% (p < 0.0001).
This decrease was independent of age. Dabigatran was the most common non-VKA OAC
(NOAC) (40% users), but usage decreased from 2014 until study end (6%) (p <
0.0001). Apixaban was the most used OAC at study end (41%), in particular among
those >=85 years (44%). Compared with patients aged <65 years, the odds ratios
associated with initiating VKA, dabigatran, rivaroxaban, or apixaban for patients
aged >=85 years were 0.81 (95% CI 0.75-0.86), 0.65 (95% CI 0.60-0.70), 1.52 (95%
CI 1.38-1.67), and 2.09 (95% CI 1.89-2.30), respectively. In conclusion,
substantial increase in NOAC usage has occurred. Increasing age was associated
with upstart of rivaroxaban or apixaban with reference to age <65 within the
specific agent.
PMID- 27510921
TI - Two-Dimensional Supramolecular Polymers Embodying Large Unilamellar Vesicles in
Water.
AB - We hereby describe a strategy for obtaining novel topological nanostructures
consisting of dual-cavity basket 1, forming a curved monolayer of large
unilamellar vesicles in water (CAC < 0.25 MUM), and bivalent guests 4/5
populating the cavities of such bolaamphiphilic hosts. On the basis of the
results of (1)H NMR spectroscopy, electron microscopy, and dynamic light
scattering measurements, we postulated that divalent guest molecules 4/5 cover
the curved vesicular surface in a lateral fashion to satisfy the complexation [2
+ 2] valency and thereby give stable two-dimensional supramolecular polymers
[1?4]n and [1?5]n. The results of experimental studies are also supported with
coarse-grained molecular dynamics simulations and molecular mechanics. Our
discovery about the assembly of novel vesicular structures could be of interest
for stabilization/functionalization of liposomal surfaces as well as detection of
polyvalent molecules and removal of targeted substances from aqueous
environments.
PMID- 27510923
TI - Cancer stem cells and epithelial-mesenchymal transition: Novel therapeutic
targets for cancer.
AB - Despite the development of various therapeutic approaches, recurrence and
metastasis remain major problems for patients with advanced cancer. Recent
studies have shown that cancer stem cells (CSCs) play an important role in cancer
aggressiveness. In cancer tissues, a small number of CSCs are able to self-renew
and differentiate into heterogeneous cancer cells. CSCs usually remain in the
resting phase of the cell cycle and possess efficient drug efflux pathways. Thus,
they are resistant to chemoradiotherapy and surviving CSCs contribute to
recurrence. During cancer metastasis, CSCs undergo epithelial-mesenchymal
transition (EMT), thereby acquiring mesenchymal features, migrating to adjacent
stromal tissues, and invading blood or lymph vessels. Recent studies showed that
EMT-inducible factors also enhance or induce CSC-like features in cancer cells.
These findings suggest that EMT is closely correlated with cancer recurrence and
metastasis. Inhibition of nestin, a CSC marker, reduces the aggressiveness of
several types of cancer. Suppression of the mesenchymal variant of fibroblast
growth factor (FGFR)-2, FGFR-2 IIIc, and regulation of the EMT using epithelial
splicing regulatory protein 1 (ESRP1) are effective in the treatment of
immunodeficient mice with pancreatic cancer. The roles of CSCs and EMT in cancer
and possible therapies are discussed in this review.
PMID- 27510922
TI - Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked
by ATG9 vesicles.
AB - Autophagosome formation requires sequential translocation of autophagy-specific
proteins to membranes enriched in PI3P and connected to the ER. Preceding this,
the earliest autophagy-specific structure forming de novo is a small punctum of
the ULK1 complex. The provenance of this structure and its mode of formation are
unknown. We show that the ULK1 structure emerges from regions, where ATG9
vesicles align with the ER and its formation requires ER exit and coatomer
function. Super-resolution microscopy reveals that the ULK1 compartment consists
of regularly assembled punctate elements that cluster in progressively larger
spherical structures and associates uniquely with the early autophagy machinery.
Correlative electron microscopy after live imaging shows tubulovesicular
membranes present at the locus of this structure. We propose that the nucleation
of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and
the ATG9 compartment.
PMID- 27510924
TI - Development and validation of a multiplex methylation specific PCR-coupled liquid
bead array for liquid biopsy analysis.
AB - BACKGROUND: Liquid biopsy is based on minimally invasive blood tests and has the
potential to characterize the evolution of a solid tumor in real time, by
extracting molecular information from circulating tumor cells (CTCs) and
circulating tumor DNA (ctDNA). Epigenetic silencing of tumor and metastasis
suppressor genes plays a key role in survival and metastatic potential of cancer
cells. Our group was the first to show the presence of epigenetic alterations in
CTCs. METHODS: We present the development and analytical validation of a highly
specific and sensitive Multiplex Methylation Specific PCR-coupled liquid bead
array (MMSPA) for the simultaneous detection of the methylation status of three
tumor and metastasis suppressor genes (CST6, SOX17 and BRMS1) in liquid biopsy
material (CTCs, corresponding ctDNA) and paired primary breast tumors. RESULTS:
In the EpCAM-positive CTCs fraction we observed methylation of: a) CST6, in
11/30(37%) and 11/30(37%), b) BRMS1 in 8/30(27%) and 11/30(37%) c) SOX17 in
8/30(27%) and 13/30(43%) early breast cancer patients and patients with verified
metastasis respectively. In ctDNA we observed methylation of: a) CST6, in
5/30(17%) and 10/31(32%), b) BRMS1 in 8/30 (27%) and 8/31 (26%) c) SOX17 in
5/30(17%) and 13/31(42%) early breast cancer patients and patients with verified
metastasis respectively. CONCLUSIONS: Our results indicate a high cancerous load
at the epigenetic level in EpCAM-positive CTCs fractions and corresponding ctDNA
in breast cancer. The main principle of the developed methodology has the
potential to be extended in a large number of gene-targets and be applied in many
types of cancer.
PMID- 27510925
TI - Disappearing the asylum: Modernizing psychiatry and generating manpower in India.
AB - In recent years, the Movement for Global Mental Health (MGMH) and the World
Health Organization have worked closely with governments across the global South
to redress major treatment gaps to improve access to mental health services. In
India, recent reforms include transforming public psychiatric institutions from
sites of treatment to research and training institutes, known as "Centres of
Excellence," to combat acute manpower shortages and modernize psychiatry. Drawing
on ethnographic fieldwork at a public psychiatric hospital in Srinagar, Kashmir,
one of the institutions selected to be a future "Centre of Excellence," this
article focuses on how these reforms have affected psychiatric institutions
themselves. Efforts at modernizing and increasing access to mental health care
that is, emphasizing shortened stays, increasing outpatient treatment, and
providing care in the "community"-depend on quarantining stigmatized, chronically
ill, long-term patients who reside in custodial conditions with fewer resources
and limited attention from providers. Psychiatrists have a radically different
vision for redressing manpower shortages than the MGMH and Indian state,
revealing contradictions in the reform process. This paper demonstrates how
modernizing mental health care splits mental institutions spatially,
ontologically, temporally, and epistemologically, so that the process of
modernizing the institution is neither seamless nor complete.
PMID- 27510926
TI - Does culture impact on notions of criminal responsibility and action? The case of
spirit possession.
AB - Multicultural societies such as the United Kingdom are host to people with
diverse belief systems and behavioral norms. Whilst a country requires that all
members of society conform to standardized legal requirements, cases arise that
involve certain complexities related to the cultural or religious context in
which a certain action was committed. This paper addresses the impact of culture
on notions of criminal responsibility and action. Through a case study of a
recent event in the United Kingdom, we explore whether a cultural defense is
relevant for contextualizing incidents in which an individual commits a criminal
action during an alleged period of spirit possession From this analysis, we
suggest that using a cultural defense can aid understanding of an individual's
relationship to the society that he or she identifies with and facilitate the
practice of justice in a multicultural society.
PMID- 27510927
TI - The relationship between chronic conditions and absenteeism and associated costs
in Canada.
AB - OBJECTIVES: This study aimed to measure and compare the relationship between
chronic diseases and the number of absent workdays due to health problems and the
associated costs among working Canadians. METHODS: The study sample included
respondents to the 2010 Canadian Community Health Survey between aged 15-75 years
who reported employment in the past three months. Respondents reported their
number of absent workdays due to health problems and chronic conditions. A
negative binomial regression was used to estimate the incremental absent workdays
associated with having a particular chronic condition (of 16 conditions),
conditional on other chronic conditions and confounders. For each condition, we
calculated the incremental number of absent workdays, the incremental
productivity loss attributed to absenteeism per employee, and the overall
productivity loss in the population. RESULTS: The final sample consisted of 28
678 respondents representing 15 468 788 employed Canadians. The average number of
absent workdays due to health problems was 1.35 days over a 3-month period. The
three conditions with the greatest association with absent workdays were mood
disorders, heart disease, and bowel disorders. They were associated with 1.17,
0.81, and 0.80 additional absent workdays, respectively, compared to workers
without this condition, holding other conditions and confounders at their means.
At the national working population level, back problems (CAD$621 million), mood
disorders (CAD$299 million) and migraine (CAD$245 million) accounted for the
largest incremental productivity loss. CONCLUSIONS: Chronic conditions,
especially mood disorders and back problems, are associated with substantial work
productivity loss. The study findings can help policy-makers and employers
prioritize their programs and resources aimed at reducing absenteeism among the
working population with chronic conditions.
PMID- 27510928
TI - Endogenous non-retroviral RNA virus elements evidence a novel type of antiviral
immunity.
AB - Vertebrate genomes contain many virus-related sequences derived from both
retroviruses and non-retroviral RNA and DNA viruses. Such non-retroviral RNA
sequences are possibly produced by reverse-transcription and integration of viral
mRNAs of ancient RNA viruses using retrotransposon machineries. We refer to this
process as transcript reversion. During an ancient bornavirus infection,
transcript reversion may have left bornavirus-related sequences, known as
endogenous bornavirus-like nucleoproteins (EBLNs), in the genome. We have
recently demonstrated that all Homo sapiens EBLNs are expressed in at least one
tissue. Because species with EBLNs appear relatively protected against infection
by a current bornavirus, Borna disease virus, it is speculated that EBLNs play
some roles in antiviral immunity, as seen with some endogenous retroviruses.
EBLNs can function as dominant negative forms of viral proteins, small RNAs
targeting viral sequences, or DNA or RNA elements modulating the gene expression.
Growing evidence reveals that various RNA viruses are reverse-transcribed and
integrated into the genome of infected cells, suggesting transcript reversion
generally occurs during ongoing infection. Considering this, transcript reversion
mediated interference with related viruses may be a novel type of antiviral
immunity in vertebrates. Understanding the biological significance of transcript
reversion will provide novel insights into host defenses against viral
infections.
PMID- 27510929
TI - Much Ado about Something: Cuban Biotech.
AB - Cuban advances in biotech have made headlines, particularly since the US-Cuba
rapprochement and signing of the historic memorandum of understanding between the
US Department of Health and Human Services and Cuba's Ministry of Public Health
in June. Some 34 Cuban institutions with 22,000 employees are the backbone of a
biotech industry that dates to the early 1980s, obtaining novel products that
have sparked interest among potential global partners. While a number of these
Cuban products are registered in various countries, their testing in the USA
remains ensnared in the red tape of embargo laws that tend to make investors
skittish and thus delay, if not curtail, joint research and clinical trial
applications to the FDA.
PMID- 27510930
TI - Charting the Course to Universal Health in the Americas: Cristian Morales PhD,
PAHO/WHO Representative in Cuba.
AB - After leaving Chile during the Pinochet era, Dr Morales studied economics, health
administration and international health at the University of Montreal. But his
baptism in the field came in Haiti, where he was first PAHO advisor to the health
ministry, and then for five years was responsible for human resources and health
economics in the PAHO offices in the capital of Port-au-Prince. He was at his
post during the flooding in Gonaives, five hurricanes, the 2010 earthquake and
the ensuing cholera epidemic-doubtless the most dramatic and complex times for
the country's health in recent history. Before becoming the PAHO/WHO
Representative in Cuba in 2015, he was Regional Advisor in Financing and Health
Economics based in Washington, DC. In that role, he plunged into the often thorny
debates about just how far governments of the Americas were willing to go towards
achieving universal health-universal coverage plus universal access. The result
was a historic resolution passed in late 2014 by PAHO's Directing Council
(CD53.R14 Strategy for Universal Access to Health and Universal Health Coverage).
Dr Morales talks about the process, the outcomes... and the road ahead.
PMID- 27510931
TI - The ABCs of Clinical Trials in Cuba.
AB - In 1981, Cuba's biotechnology sector was born when Cuban scientists, trained by
Finnish colleagues, successfully isolated large quantities of human leukocyte
interferon alpha. Within a decade and following a $1-billion dollar investment by
the Cuban government, 52 scientific research institutions were established in and
around Havana to develop vaccines, therapies and other medical applications to
meet demands of the national health system.
PMID- 27510932
TI - Epidemiology of Suicide in Cuba, 1987-2014.
AB - INTRODUCTION Suicide is a health problem influenced by biological, genetic,
psychological, social and economic factors. It is responsible for 50% of violent
deaths in the male population, worldwide, and 71% in the female. In the Americas,
65,000 deaths by suicide occur every year. It is the ninth most frequent cause of
death in Cuba, and third among people aged 10-19. OBJECTIVE Characterize the
epidemiology of suicide in Cuba from 1987 to 2014. METHODS A retrospective
descriptive study was conducted. The information comprised all records of death
by suicide from January 1, 1987 to December 31, 2014, in the Cuban Ministry of
Public Health's National Statistics Division database. The variables were sex,
age, skin color, employment status/occupation, marital status, and method of
suicide. Crude and age-standardized mortality rates and age-sex specific
mortality rates were calculated, all per 100,000 population, as well as the sex
ratio. Relative change over the series was calculated as a percentage.
Distribution of suicides by variable was calculated and proportions expressed as
percentages. RESULTS A total of 51,113 deaths by suicide were reported (annual
average 1825), of which 34,671 (67.8%) were among men. The sex ratio was 2.1:1
for the entire study period, and 3.9:1 for 2011-2014. Over the course of the
period studied, age-standardized suicide rates decreased from 23.9 to 10.8 per
100,000 population (54.8% reduction). The group aged >=60 years had the highest
average age-standardized rate, 44.6 per 100,000 population. The highest suicide
burden by age was in the group aged 20-59 years (60.5%). By skin color, the
highest burden was in those recorded as white, 68.9%. By marital status, the
highest burden was in persons with a stable partner (46.7%), and by employment
status/occupation, in retired (25.9%). The most commonly used method was hanging
(59.4%). CONCLUSIONS Over the course of about three decades, suicide mortality
rates have declined by almost half and they are still slightly higher than
overall rates in the Americas. The most commonly used method is hanging. The sex
ratio is greater than two and has increased over time. The highest rates occur in
the group aged >=60 years, but finer stratification is needed to identify an age
related risk trend. In view of Cuba's aging population, these results are of
interest for epidemiology and public health. KEYWORDS Suicide, suicide attempt,
death, mental health, Cuba.
PMID- 27510933
TI - Improving Disability Care in Countries of the Bolivarian Alliance for the Peoples
of Our America.
AB - Persons with disabilities constitute one of the most vulnerable groups in every
society; their identification, assessment and care present a major challenge. In
2001-2003, Cuba conducted the first comprehensive national study of persons with
disabilities in the Americas. In 2007-2010, the study was replicated in Bolivia,
Ecuador, Nicaragua, Saint Vincent and the Grenadines, and Venezuela, at their
governments' request. Study results have enabled implementation of strategies
with substancial impact on human health in these countries. In response to it,
more than a million medical consultations were provided by professionals whose
specialties are lacking in the participating countries, including 139,772
clinical genetic consultations. Once each country's needs were identified, Cuba
provided technical assistance with equipment supplied by Venezuela. The study led
to development of public policies and programs for disability prevention and care
of disabled persons in Bolivia, Ecuador, Nicaragua and Venezuela, and the opening
of the National Medical Genetics Center and orthotic and prosthetic laboratories
in Venezuela, and rehabilitation centers in Bolivia. KEYWORDS Disability,
epidemiology, health services research, needs assessment, human resources,
workforce, Bolivia, Cuba, Ecuador, Nicaragua, Saint Vincent and the Grenadines,
Venezuela.
PMID- 27510934
TI - An Intersectoral Intervention to Prevent Early Alcohol Use in Cuban Adolescents.
AB - To encourage development of negative attitudes toward alcohol use and thus
prevent early onset of alcohol use, an intersectoral intervention was conducted
from 2014 to 2015 among Cuban adolescents in 14 schools in Havana. The
intervention included 312 students (189 girls and 123 boys) aged 14 to 15 years
in 10th grade of high school or vocational school. Workshops were conducted using
participatory techniques and group dynamics. Qualitative methods were applied,
including narrative, desiderative and projective techniques. Indicators included
attitudes, motivation, interests and perception of risk. Following the
intervention, 82.7% (258/312) of participants reported healthy cultural and
recreational interests and 61.9% (193/312) reinforced negative attitudes toward
drinking. Such interventions can help prevent early onset of alcohol use in
school settings. Given the positive results, the intervention is slated to be
reproduced in other Cuban provinces. KEYWORDS Adolescents, prevention,
alcoholism, attitudes, Cuba.
PMID- 27510935
TI - Alcohol Control in Cuba: Preventing Countervailing Cultural and Mass Media
Influences.
AB - Harmful use of alcohol-the prime gateway drug to other addictions-is also a
problem in Cuba, even though the National Program for Prevention of Harmful Use
of Alcohol includes the most effective measures used in analogous programs around
the world. As a participant in the program's committee and empirical observer of
its accomplishments and unaccomplished goals, I draw attention to the community's
attitude of tolerance toward intoxication manifested by the lack of proportional
consequences, and I insist on the need to broaden the community's understanding
of the risks of non-social drinking, which in Latin America is practically
limited to alcoholism and its complications. This undervalues the damage wreaked
by unpredictable and dangerous behavior under the influence, as well as the
suffering of codependents and other "passive drinkers," and the adverse effects
of even social drinking. KEYWORDS Alcohol abuse/prevention and control, alcohol
consumption, alcohol drinking/culture, alcoholism, drinking behavior, behavior
and behavior mechanisms, social determinants of health, social reinforcement,
mass media, communication, Cuba.
PMID- 27510936
TI - Saharan Dust Effects on Human Health: A Challenge for Cuba's Researchers.
AB - WHO considers the effects of air pollution one of the most pressing global health
priorities. Several years ago, scientists began noting a link between Saharan
dust (a meteorological phenomenon that diminishes air quality as it spreads over
the globe) and some diseases, but the few studies to date have been inconsistent.
Cuba has the human and material resources to study the association between
Saharan dust and health. It is important to encourage creation of
multidisciplinary research teams to do so. KEYWORDS Health, airborne particulate
matter, dust, air pollutants, environmental health, climate, Cuba.
PMID- 27510937
TI - Controversies in Screening and Diagnosis of Gestational Diabetes: Cuba's
Position.
AB - Gestational diabetes is the most common endocrine disorder affecting pregnant
women and its prevalence is on the rise. Prevalence in Cuba is about 5.8%, and
global prevalence ranges from 2% to 18% depending on the criteria applied.
Gestational diabetes can lead to adverse gestational outcomes, such as fetal
death, preterm delivery, dystocia, perinatal asphyxia and neonatal complications.
Prompt, accurate diagnosis allowing early treatment can benefit both mother and
child. The disease is asymptomatic, so clinical laboratory testing plays a key
role in its screening and diagnosis. Cuba's approach to diabetes screening and
diagnosis differs from some international practices. All pregnant women in Cuba
are screened with a fasting plasma glucose test and diagnosed using modified WHO
criteria. Some international recommendations are to skip the screening step and
instead follow the diagnostic criteria of the Hyperglycemia and Adverse Pregnancy
Outcomes study. In Cuba, gestational outcomes for women with diabetes (including
gestational diabetes) are satisfactory (preeclampsia 5%; preterm delivery 12%;
neonatal macrosomia 7.5%; congenital abnormalities 4.3% and perinatal deaths
4.8%). These data do not indicate a need to change established screening and
diagnostic criteria. KEYWORDS Gestational diabetes, screening, diagnosis, early
detection, early diagnosis, Cuba.
PMID- 27510938
TI - Havana: A Bike-Friendly City?
AB - The abrupt breakup of the USSR and socialist bloc in the early 1990s dealt a
devastating blow to the island's economy. Almost overnight, beneficial aid and
trade provided by the Council for Mutual Economic Assistance ground to a halt,
including 80% of foreign trade previously conducted as barter and sales of 13
million tons of oil per year at preferential prices. When the Cuban economy
bottomed out in 1993, oil imports had dropped from 13 to 4 million tons annually.
At the time, Cuba depended almost entirely on imported oil and the dramatic
decline in imports created massive blackouts, leaving most Cuban homes without
electricity 12 hours a day.
PMID- 27510939
TI - Immediate and delayed signal of slab breakoff in Oligo/Miocene Molasse deposits
from the European Alps.
AB - High-resolution 32-20 Ma-old stratigraphic records from the Molasse foreland
basin situated north of the Alps, and Gonfolite Lombarda conglomerates deposited
on the southern Alpine margin, document two consecutive sedimentary responses -
an immediate and delayed response - to slab breakoff beneath the central Alps c.
32-30 Ma ago. The first signal, which occurred due to rebound and surface uplift
in the Alps, was a regional and simultaneous switch from basin underfill to
overfill at 30 Ma paired with shifts to coarse-grained depositional environments
in the foreland basin. The second signal, however, arrived several million years
after slab breakoff and was marked by larger contributions of crystalline clasts
in the conglomerates, larger clast sizes, larger sediment fluxes and shifts to
more proximal facies. We propose that this secondary pulse reflects a delayed
whiplash-type erosional response to surface uplift, where erosion and sediment
flux became amplified through positive feedbacks once larger erosional thresholds
of crystalline bedrock were exceeded.
PMID- 27510940
TI - Single scrotal incision orchiopexy versus the inguinal approach in children with
palpable undescended testis: a systematic review and meta-analysis.
AB - PURPOSE: We performed a systematic review and meta-analysis to compare the
efficacy and safety between single-incision, transscrotal orchidopexy, and the
traditional inguinal orchidopexy in children. METHODS: A systematic search of the
electronic databases was conducted to identify studies compared the transscrotal
orchidopexy (SO) and inguinal orchidopexy (IO) for children. Parameters, such as
operative time, the incidence of patent processus vaginalis, and postoperative
complications, including wound infection, testicular atrophy, testicular
reascent, hernia, or hydrocele, were pooled and compared by meta-analysis.
RESULTS: Among the 1376 children with palpable undescended testes (UDTs) included
in the eight studies, 697 had received SO and 679 IO. There were shorter
operative times with the SO approach compared with IO. However, no significant
difference was found between SO and IO in the incidence of patent processus
vaginalis and postoperative complications, including wound infection, testicular
atrophy, testicular reascent, and hernia. CONCLUSION: SO is a safe and effective
surgical approach alternative to IO for pediatric UDTs. Compared with IO, SO has
the advantage of shorter operative times. Besides, the incidence of postoperative
wound infection may be slightly lower in SO. We suggest that SO should be
considered as an acceptable option for children with UDTs.
PMID- 27510941
TI - AIEgens-Functionalized Inorganic-Organic Hybrid Materials: Fabrications and
Applications.
AB - Inorganic materials functionalized with organic fluorescent molecules combine
advantages of them both, showing potential applications in biomedicine,
chemosensors, light-emitting, and so on. However, when more traditional organic
dyes are doped into the inorganic materials, the emission of resulting hybrid
materials may be quenched, which is not conducive to the efficiency and
sensitivity of detection. In contrast to the aggregation-caused quenching (ACQ)
system, the aggregation-induced emission luminogens (AIEgens) with high solid
quantum efficiency, offer new potential for developing highly efficient inorganic
organic hybrid luminescent materials. So far, many AIEgens have been incorporated
into inorganic materials through either physical doping caused by aggregation
induced emission (AIE) or chemical bonding (e.g., covalent bonding, ionic
bonding, and coordination bonding) caused by bonding induced emission (BIE)
strategy. The hybrid materials exhibit excellent photoactive properties due to
the intramolecular motion of AIEgens is restricted by inorganic matrix. Recent
advances in the fabrication of AIEgens-functionalized inorganic-organic hybrid
materials and their applications in biomedicine, chemical sensing, and solid
state light emitting are presented.
PMID- 27510942
TI - Managing Migraine.
PMID- 27510943
TI - Exacerbation of Hailey-Hailey disease by topiramate.
PMID- 27510944
TI - Functional dissociation between anterior temporal lobe and inferior frontal gyrus
in the processing of dynamic body expressions: Insights from behavioral variant
frontotemporal dementia.
AB - Several brain regions are involved in the processing of emotional stimuli,
however, the contribution of specific regions to emotion perception is still
under debate. To investigate this issue, we combined behavioral testing,
structural and resting state imaging in patients diagnosed with behavioral
variant frontotemporal dementia (bvFTD) and age matched controls, with task-based
functional imaging in young, healthy volunteers. As expected, bvFTD patients were
impaired in emotion detection as well as emotion categorization tasks, testing
dynamic emotional body expressions as stimuli. Interestingly, their performance
in the two tasks correlated with gray matter volume in two distinct brain
regions, the left anterior temporal lobe for emotion detection and the left
inferior frontal gyrus (IFG) for emotion categorization. Confirming this
observation, multivoxel pattern analysis in healthy volunteers demonstrated that
both ROIs contained information for emotion detection, but that emotion
categorization was only possible from the pattern in the IFG. Furthermore,
functional connectivity analysis showed reduced connectivity between the two
regions in bvFTD patients. Our results illustrate that the mentalizing network
and the action observation network perform distinct tasks during emotion
processing. In bvFTD, communication between the networks is reduced, indicating
one possible cause underlying the behavioral symptoms. Hum Brain Mapp 37:4472
4486, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27510945
TI - Evidence-Based Continence Care: An Integrative Review.
AB - PURPOSE: The purpose of this integrative review is to identify the best nurse
managed continence care strategies among rehabilitation patients from the current
body of evidence. DESIGN: The newly designed 2015 Competency Model for
Professional Rehabilitation Nursing serves as a conceptual framework to
categorize evidence-based recommendations for continence care into the four
domains of the model. METHODS: A search of the evidence was completed in December
2015. Literature reviewed was limited to articles published from 2005-2015 in the
English language. Search priority was given to systematic reviews and randomized
controlled trials. FINDINGS: Nurse-led interventions include evidence-based
clinical assessments with use of validated instruments following step-wise
algorithms derived from clinical practice guidelines. The interprofessional team
emphasizes role-based continence interventions with shared work to reach goals.
Leadership recommendations call for administrative support and allocation of
resources for continence care and also empower select bedside nurses to become
continence champions. Finally, nurse-patient education and caregiver training
target the promotion of successful living. System-based continence
recommendations are identified to include rehab-oriented electronic documentation
systems, written continence policies and procedures, and ongoing nursing
education emphasizing accountability to high performance standards. CONCLUSIONS:
Rehabilitation nurses are the team leaders in promoting continence in the
rehabilitation setting. They are the cultivators of hope and foster resilience
among patients to move forward despite acute or chronic illness and disability.
This article is intended to support rehabilitation nurses in their review of
clinical evidence in effort to move toward a more uniform approach to bowel and
bladder management. CLINICAL RELEVANCE: This review equips rehabilitation nurses
who seek to improve their practice by identifying the best evidence-based
approaches to continence care.
PMID- 27510946
TI - Rapid pacing using the left ventricular guidewire: Reviving an old technique to
simplify BAV and TAVI procedures.
AB - OBJECTIVES: We sought to demonstrate the safety and efficacy of rapid left
ventricular (LV) pacing through the guidewire during balloon aortic valvuloplasty
(BAV) and Transaortic valve implantation (TAVI). BACKGROUND: Right ventricular
temporary pacing during TAVI and BAV is time-consuming and associated with
vascular and pericardial complications. METHODS: Rapid left ventricular pacing
was provided via the back-up 0.035" guidewire. The cathode of an external
pacemaker was placed on the tip of the 0.035" wire and the anode on a needle
inserted into the groin. Insulation was ensured by the balloon or TAVI catheter.
RESULTS: 38 BAV and 87 TAVI procedures were performed in 113 consecutive patients
in three centers with one for one pacing (160-200 bpm) in all patients. A
significant reduction in blood pressure was achieved with a mean systolic
pressure of 44 mm Hg during stimulation. Mean procedural time was 49.7 +/- 31 min
for BAV and 68.7 +/- 30.9 for TAVI. A temporary venous pacemaker was required in
12 patients; only 12% of TAVI patients had a femoral central venous catheter.
Femoral venous puncture was not performed in BAV patients. No venous vascular
complications were observed. One case of successfully treated tamponade (0.8%)
occurred 8 hr post procedure. In-hospital mortality rates were 4.6% and 2.6% in
the TAVI and BAV groups, respectively. CONCLUSIONS: Use of the LV guidewire for
rapid pacing during BAV and TAVI was shown to be simple, reproducible, and
prevented complications associated with RV temporary leads thus potentially
simplifying TAVI and enhancing its safety. (c) 2016 Wiley Periodicals, Inc.
PMID- 27510947
TI - Design-corrected variation by centre in mortality reduction in the ERSPC
randomised prostate cancer screening trial.
AB - Objectives To calculate design-corrected estimates of the effect of screening on
prostate cancer mortality by centre in the European Randomised Study of Screening
for Prostate Cancer (ERSPC). Setting The ERSPC has shown a 21% reduction in
prostate cancer mortality in men invited to screening with follow-up truncated at
13 years. Centres either used pre-consent randomisation (effectiveness design) or
post-consent randomisation (efficacy design). Methods In six centres (three
effectiveness design, three efficacy design) with follow-up until the end of
2010, or maximum 13 years, the effect of screening was estimated as both
effectiveness (mortality reduction in the target population) and efficacy
(reduction in those actually screened). Results The overall crude prostate cancer
mortality risk ratio in the intervention arm vs control arm for the six centres
was 0.79 ranging from a 14% increase to a 38% reduction. The risk ratio was 0.85
in centres with effectiveness design and 0.73 in those with efficacy design.
After correcting for design, overall efficacy was 27%, 24% in pre-consent and 29%
in post-consent centres, ranging between a 12% increase and a 52% reduction.
Conclusion The estimated overall effect of screening in attenders (efficacy) was
a 27% reduction in prostate cancer mortality at 13 years' follow-up. The
variation in efficacy between centres was greater than the range in risk ratio
without correction for design. The centre-specific variation in the mortality
reduction could not be accounted for by the randomisation method.
PMID- 27510949
TI - A model of tissue contraction during thermal ablation.
AB - A model of a globular protein is used to describe the contraction of tissue
exposed to elevated temperatures. This will be useful in predicting the
contraction of tissue that is observed during thermal ablation of tumours, which
is a problem when trying to determine the ablation zone in post-operative images.
The transitions between the states of the protein can be related to a change in
the length of the molecule, which can be directly observed as a change in the
length of the tissue. A three state model of a globular protein is used to
describe the contraction of tissue exposed to elevated temperatures. A nonlinear
fitting algorithm is considered here to fit available experimental data and thus
to obtain the values of the model parameters. A sensitivity analysis of the
proposed mathematical model is performed to determine the most important
parameters in the model. The model parameters were obtained from experimental
data of isothermal free shrinkage experiments. The predictions of the complete
model show similar agreement with the data, well within the experimental error of
10%. The overall activation energy and frequency factor were found to be 201 kJ
mol(-1) and [Formula: see text] s(-1) respectively. The results show that the
experimental data were well described by the three state model considered here.
Furthermore, it was possible to determine the most sensitive parameters in the
model. The model presented here will allow predictions of thermal ablation to be
corrected for tissue shrinkage, thus improving mathematical simulations for
treatment planning, although clinical translation will require adapting the model
from experimentally obtained tendon data to soft tissue data.
PMID- 27510948
TI - Cellular model of neuronal atrophy induced by DYNC1I1 deficiency reveals
protective roles of RAS-RAF-MEK signaling.
AB - Neuronal atrophy is a common pathological feature occurred in aging and
neurodegenerative diseases. A variety of abnormalities including motor protein
malfunction and mitochondrial dysfunction contribute to the loss of neuronal
architecture; however, less is known about the intracellular signaling pathways
that can protect against or delay this pathogenic process. Here, we show that the
DYNC1I1 deficiency, a neuron-specific dynein intermediate chain, causes neuronal
atrophy in primary hippocampal neurons. With this cellular model, we are able to
find that activation of RAS-RAF-MEK signaling protects against neuronal atrophy
induced by DYNC1I1 deficiency, which relies on MEK-dependent autophagy in neuron.
Moreover, we further reveal that BRAF also protects against neuronal atrophy
induced by mitochondrial impairment. These findings demonstrate protective roles
of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic
target for clinical intervention.
PMID- 27510950
TI - Update on the Toriello-Carey syndrome.
AB - Toriello and Carey described a provisionally-unique syndrome comprised of
agenesis of the corpus callosum, Pierre Robin anomaly, and a characteristic
facial phenotype. Because the condition affected siblings, this entity was
postulated to be an autosomal recessive multiple anomaly syndrome. Several
patients were subsequently reported, and over time, it became apparent that the
Toriello-Carey syndrome was etiologically heterogeneous. Based on previous
reports, it is estimated that at least 20% of patients with a clinical diagnosis
of Toriello-Carey syndrome have a chromosomal anomaly as the basis of the
phenotype. However, no basis for the non-chromosomal cases has been found. This
review summarizes the literature to date and provides speculation regarding the
possible explanations for failing to find the cause of Toriello-Carey syndrome.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27510951
TI - Carotid sinus denervation ameliorates renovascular hypertension in adult Wistar
rats.
AB - KEY POINTS: Peripheral chemoreflex sensitization is a feature of renovascular
hypertension. Carotid sinus nerve denervation (CSD) has recently been shown to
relieve hypertension and reduce sympathetic activity in other rat models of
hypertension. We show that CSD in renovascular hypertension halts further
increases in blood pressure. Possible mechanisms include improvements in
baroreceptor reflex sensitivity and renal function, restoration of cardiac
calcium signalling towards control levels, and reduced neural inflammation. Our
data suggest that the peripheral chemoreflex may be a viable therapeutic target
for renovascular hypertension. ABSTRACT: The peripheral chemoreflex is known to
be hyper-responsive in both spontaneously hypertensive (SHR) and Goldblatt
hypertensive (two kidney one clip; 2K1C) rats. We have previously shown that
carotid sinus nerve denervation (CSD) reduces arterial blood pressure (ABP) in
SHR. In the present study, we show that CSD ameliorates 2K1C hypertension and
reveal the potential underlying mechanisms. Adult Wistar rats were instrumented
to record ABP via telemetry, and then underwent CSD (n = 9) or sham CSD (n = 9) 5
weeks after renal artery clipping, in comparison with normal Wistar rats (n = 5).
After 21 days, renal function was assessed, and tissue was collected to assess
sympathetic postganglionic intracellular calcium transients ([Ca2+ ]i ) and
immune cell infiltrates. Hypertensive 2K1C rats showed a profound elevation in
ABP (Wistar: 98 +/- 4 mmHg vs. 2K1C: 147 +/- 8 mmHg; P < 0.001), coupled with
impairments in renal function and baroreflex sensitivity, increased
neuroinflammatory markers and enhanced [Ca2+ ]I in stellate neurons (P < 0.05).
CSD reduced ABP in 2K1C+CSD rats and prevented the further progressive increase
in ABP seen in 2K1C+sham CSD rats, with a between-group difference of 14 +/- 2
mmHg by week 3 (P < 0.01), which was accompanied by improvements in both
baroreflex control and spectral indicators of cardiac sympatho-vagal balance.
Furthermore, CSD improved protein and albuminuria, decreased [Ca2+ ]i evoked
responses from stellate neurons, and also reduced indicators of brainstem
inflammation. In summary, CSD in 2K1C rats reduces the hypertensive burden and
improves renal function. This may be mediated by improvements in autonomic
balance, functional remodelling of post-ganglionic neurons and reduced
inflammation. Our results suggest that the peripheral chemoreflex may be
considered as a potential therapeutic target for controlling renovascular
hypertension.
PMID- 27510952
TI - Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in
glioblastoma cells in vitro and in vivo.
AB - Even with aggressive treatment involving radiation therapy plus temozolomide
(TMZ), the prognosis for glioblastoma remains poor. We investigated the potential
for targeting signal transducer and activator of transcription-3 (STAT3) to
improve the therapeutic outcome in glioblastoma. We evaluated the preclinical
potential of a STAT3 inhibitor, Cpd188, combined with temozolomide and radiation
using in vitro assays with two established glioblastoma cell lines (U251 and U87)
and two patient-derived glioblastoma cell lines (GBL12 and GBL28) as well as in
vivo studies with nude mice bearing intracranial U251 xenografts. Cpd188
potentiated the radiosensitizing effect of TMZ in U251 cells, which have high p
STAT3 expression levels. The enhanced radiosensitizing effects of TMZ were
associated with impaired DNA damage repair, apoptosis and reversion of the
epithelial-mesenchymal transition (EMT). Cpd188 delayed in vivo tumor growth
alone and in combination with radiation and TMZ. We also confirmed the
radiosensitizing effect of Cpd188 in GBL28 cells, which were originated from a
patient with a high level of STAT3 expression and unmethylated MGMT. Targeting
STAT3 using Cpd188 could be a viable therapeutic approach for improving the
outcome of current standard therapy in glioblastoma patients with high p-STAT3
expression.
PMID- 27510953
TI - Migrating glioma cells express stem cell markers and give rise to new tumors upon
xenografting.
AB - Glioblastoma (GBM) is the most frequent and malignant brain tumor with an overall
survival of only 14.6 months. Although these tumors are treated with surgery,
radiation and chemotherapy, recurrence is inevitable. A critical population of
tumor cells in terms of therapy, the so-called cancer stem cells (CSCs), has been
identified in gliomas and many other cancers. These tumor cells have a stem cell
like phenotype and are suggested to be responsible for tumor growth, chemo- and
radio-resistance as well as recurrence. However, functional evidence for
migrating glioma cells having a stem cell-like phenotype is currently lacking. In
the present study, the aim was to characterize the phenotype of migrating tumor
cells using a novel migration assay based on serum-free stem cell medium and
patient-derived spheroid cultures. The results showed pronounced migration of
five different GBM spheroid cultures, but not of the commercial cell line U87MG.
An in vitro limiting dilution assay showed preserved but reduced spheroid
formation capacity of migrating cells. Orthotopic xenografting in mice showed
preserved but reduced tumorigenic capacity. Profiling of mRNAs revealed no
significant deregulation of 16 predefined CSC-related genes and the HOX-gene list
in migrating cells compared to spheroids. Determination of GBM molecular subtypes
revealed that subtypes of spheroids and migrating cells were identical. In
conclusion, migrating tumor cells preserve expression of stem cell markers and
functional CSC characteristics. Since CSCs are reported to be highly resistant to
therapy, these results emphasize that the CSC phenotype should be taken into
consideration in future treatment of GBMs.
PMID- 27510954
TI - Detection and molecular characterization of Torque Teno Virus (TTV) in Uruguay.
AB - Torque Teno Virus (TTV), member of Anelloviridae family, is considered a
worldwide distributed emergent virus and is currently classified into seven
genogroups. Interestingly, the pathogenicity of TTV remains unclear. However, it
has been constantly associated to hepatitis cases of unknown etiology (HUE) as
well as extensively studied in concurrent infections with Hepatitis B Virus
(HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus type 1 (HIV-1).
In South America, TTV epidemiological data is scant, involving some studies from
Brazil, Venezuela, Colombia and Bolivia. The aim of this work was to investigate
for the first time in Uruguay the presence of TTV by a nested-PCR system in 85
human serum samples infected with HBV and/or HCV and/or HIV-1 and in HUE cases.
Overall, our results reported a TTV infection rate of 79% (67/85). Furthermore,
the molecular characterization of Uruguayan strains revealed that one of them
clustered in genogroup 1, while the remaining ones formed separate clusters
closely related to genogroup 3, which should be confirmed by complete genome
sequencing. Further investigation about TTV circulation in Uruguayan population
is needed in order to provide additional information about the genetic
variability and TTV epidemiology in South America.
PMID- 27510955
TI - Barriers to HIV Medication Adherence as a Function of Regimen Simplification.
AB - BACKGROUND: Barriers to HIV medication adherence may differ by levels of dosing
schedules. PURPOSE: The current study examined adherence barriers associated with
medication regimen complexity and simplification. METHODS: A total of 755 people
living with HIV currently taking anti-retroviral therapy were recruited from
community services in Atlanta, Georgia. Participants completed audio-computer
assisted self-interviews that assessed demographic and behavioral
characteristics, provided their HIV viral load obtained from their health care
provider, and completed unannounced phone-based pill counts to monitor medication
adherence over 1 month. RESULTS: Participants taking a single-tablet regimen
(STR) were more likely to be adherent than those taking multi-tablets in a single
dose regimen (single-dose MTR) and those taking multi-tablets in a multi-dose
regimen (multi-dose MTR), with no difference between the latter two. Regarding
barriers to adherence, individuals taking STR were least likely to report
scheduling issues and confusion as reasons for missing doses, but they were
equally likely to report multiple lifestyle and logistical barriers to adherence.
CONCLUSIONS: Adherence interventions may need tailoring to address barriers that
are specific to dosing regimens.
PMID- 27510956
TI - Single-Session Behavioral Interventions for Sexual Risk Reduction: A Meta
Analysis.
AB - BACKGROUND: Evidence-based, single-session STI/HIV interventions to reduce sexual
risk taking are potentially effective options for implementation in resource
limited settings and may solve problems associated with poor participant
retention. PURPOSE: The purpose of the study is to estimate the efficacy of
single-session, behavioral interventions in reducing unprotected sex or
increasing condom use. METHODS: Data sources were searched through April 2013
producing 67 single-session interventions (52 unique reports; N = 20,039) that
included outcomes on condom use and/or unprotected sex. RESULTS: Overall,
participants in single-session interventions reduced sexual risk taking relative
to control groups (d + = 0.19, 95 % CI = 0.11, 0.27). Within-group effects of
the interventions were larger than the between-groups effects when compared to
controls. CONCLUSIONS: Brief, targeted single-session sexual risk reduction
interventions demonstrate a small but significant effect and should be
prioritized.
PMID- 27510957
TI - Effectiveness of temporary implants in teenage patients: a prospective clinical
trial.
AB - AIMS: The objective of this study was to assess prospectively the outcomes of
extra-narrow diameter implants (XNDI) placed in teenage patients as a temporary
restorative option. MATERIAL AND METHODS: Twenty consecutive young patients
presenting one or several missing teeth received XNDI that were immediately
restored with composite, Polymethylmethacrylate (Acrylic) or ceramic crown.
Clinical and radiographical outcomes were assessed for a minimum follow-up period
of 1 year. Additionally, each patient completed retrospectively a satisfaction
questionnaire using Visual Analog Scale (VAS). RESULTS: A total of 30 implants
were placed and followed for a period of 1-7.4 years (mean: 3.59 years). One
implant failed after 3 weeks and was replaced successfully. No further biological
complications occurred during the follow-up period, leading to an implant
survival rate of 96.6%. The patient satisfaction evaluations displayed high
levels of comfort and function. CONCLUSION: Immediately restored XNDI to replace
missing teeth on teenager patients seems to be an effective temporary restorative
option to replace missing teeth in young patients. Composite or ceramic crowns
should be preferred. Clinical trials with long-term follow-ups and the assessment
of passive egression are needed.
PMID- 27510958
TI - The role of DNA methylation in ST6Gal1 expression in gliomas.
AB - The mechanism of transcriptional silencing of ST6Gal1 in gliomas has not yet been
elucidated. Multiple independent promoters govern the expression of the ST6Gal I
gene. Here, we investigated whether epigenetic abnormalities involving DNA
methylation affect ST6Gal1 expression. Transcript-specific qRT-PCR following
exposure of glioma cell lines to 5-aza-2'-deoxycytidine (5-aza-dC), a DNA
methyltransferase inhibitor, resulted in the re-expression of the normally
quiescent ST6Gal1 mRNA driven exclusively by the P3 promoter sequence. The P3
promoter-specific transcription start site (TSS) was delineated by primer
extension and core promoter sequences and associated functional transcription
elements identified by deletion analysis utilizing chloramphenicol
acetyltransferase reporter constructs. Minimal promoter activity was found to
reside within the first 100 bp of the TSS and maximal activity was controlled by
functional AP2 binding sites residing between 400 and 500 bp upstream of the
initiation site. As altered AP2 binding was not directly associated with AP2
availability, these analyses demonstrate that ST6Gal1 transcription is regulated
by DNA methylation within core promoter regions, ultimately by determining
critical transcription factor accessibility within these regions. Transcriptional
reactivation of ST6Gal1 expression by 5-aza-dC resulted in increased cell surface
alpha2,6 sialoglycoconjugate expression, increased alpha2,6 sialylation of beta1
integrin, and decreased adhesion to fibronectin substrate: functional correlates
of decreased invasivity. The effects of global hypomethylation are not glycome
wide. Focused glycotranscriptomic analyses of three invasive glioma cell lines
following 5-aza-dC treatment demonstrated the modulation of select glycogene
transcripts. Taken together, these results demonstrate that epigenetic modulation
of ST6Gal1 expression plays a key role in the glioma phenotype in vitro and that
that therapeutic approaches targeting elements of the epigenetic machinery for
the treatment of human glioblastoma are warranted.
PMID- 27510959
TI - A Retrospective Study of thrombolysis with 0.6 mg/kg Recombinant Tissue
Plasminogen Activator (rt-PA) in Mild Stroke.
AB - We sought to assess the safety, effectiveness and cost of 0.6 mg/kg rt-PA
treatment for patients with acute mild stroke and to compare that with 0.9 mg/kg.
We retrospectively analyzed consecutive acute ischemic stroke patients who had a
NIHSS score <=5 at admission and who were treated with rt-PA within 4.5 hours of
symptom onset. The demographic data, clinical outcomes and hospitalization cost
were analyzed. A total of 108 patients were included. Forty six patients (42.6%)
received a 0.6 mg/kg dosage of rt-PA. The baseline characteristics of the two
groups were well matched (p > 0.05). Regarding the safety and effectiveness, the
0.6 mg/kg dosage group had a comparable proportion of symptomatic intracranial
hemorrhage (sICH) (0.6 mg/kg, 4.3% vs 0.9 mg/kg, 4.8%; p > 0.05), early
neurological deterioration (END) (19.6% vs 17.7%; p > 0.05), in-hospital
mortality (4.3% vs 1.6%; p > 0.05), and a similar rate of favorable functional
outcome (mRS score 0-1) at 3 months (73.9% vs 71.0%; p > 0.05) to those who
received the standard dosage. However, the hospital cost was markedly lower in
the 0.6 mg/kg group (0.6 mg/kg, 3,401.7 USD vs 0.9 mg/kg, 4,157.4 USD; p <
0.01). Our study suggest that 0.6 mg/kg rt-PA shared similar effectiveness and
safety profile compared with that of 0.9 mg/kg in treating mild stroke, but cost
less.
PMID- 27510960
TI - Effects of series elastic compliance on muscle force summation and the rate of
force rise.
AB - Compliant tendons permit mechanically unfavourable fascicle dynamics during fixed
end contractions. The purpose of this study was to reduce the effective
compliance of tendon and investigate how small reductions in active shortening
affect twitch kinetics and contractile performance in response to a second
stimulus. The series elastic element (SEE) of the human triceps surae (N=15) was
effectively stiffened by applying a 55 ms rotation to the ankle, through a range
of 5 deg, at the onset of twitch and doublet [interstimulus interval (ISI) of 80
ms] stimulation. Ultrasonography was employed to quantify lateral gastrocnemius
and soleus fascicle lengths. Rotation increased twitch torque (40-75%), rate of
torque development (RTD; 124-154%) and torque-time integral (TTI; 70-110%)
relative to constant-length contractions at the initial and final joint
positions, yet caused only modest reductions in shortening amplitude and
velocity. The torque contribution of the second pulse increased when stimulation
was preceded by rotation, a finding unable to be explained on the basis of
fascicle length or SEE stiffness during contraction post-rotation. A further
increase in torque contribution was not demonstrated, nor was an increase in
doublet TTI, when the second pulse was delivered during rotation and shortly
after the initial pulse (ISI of 10 ms). The depressant effect of active
shortening on subsequent torque generation suggests that compliant tendons, by
affording large length changes, may limit torque summation. Our findings indicate
that changes in tendon compliance shown to occur in response to resistance
training or unloading are likely sufficient to considerably alter contractile
performance, particularly maximal RTD.
PMID- 27510961
TI - Echolocation behavior in big brown bats is not impaired after intense broadband
noise exposures.
AB - Echolocating bats emit trains of intense ultrasonic biosonar pulses and listen to
weaker echoes returning from objects in their environment. Identification and
categorization of echoes are crucial for orientation and prey capture. Bats are
social animals and often fly in groups in which they are exposed to their own
emissions and to those from other bats, as well as to echoes from multiple
surrounding objects. Sound pressure levels in these noisy conditions can exceed
110 dB, with no obvious deleterious effects on echolocation performance.
Psychophysical experiments show that big brown bats (Eptesicus fuscus) do not
experience temporary threshold shifts after exposure to intense broadband
ultrasonic noise, but it is not known if they make fine-scale adjustments in
their pulse emissions to compensate for any effects of the noise. We investigated
whether big brown bats adapt the number, temporal patterning or relative
amplitude of their emitted pulses while flying through an acoustically cluttered
corridor after exposure to intense broadband noise (frequency range 10-100 kHz;
sound exposure level 152 dB). Under these conditions, four bats made no
significant changes in navigation errors or in pulse number, timing and amplitude
20 min, 24 h or 48 h after noise exposure. These data suggest that big brown bats
remain able to perform difficult echolocation tasks after exposure to
ecologically realistic levels of broadband noise.
PMID- 27510962
TI - Introducing a novel mechanism to control heart rate in the ancestral Pacific
hagfish.
AB - Although neural modulation of heart rate is well established among chordate
animals, the Pacific hagfish (Eptatretus stoutii) lacks any cardiac innervation,
yet it can increase its heart rate from the steady, depressed heart rate seen in
prolonged anoxia to almost double its normal normoxic heart rate, an almost
fourfold overall change during the 1-h recovery from anoxia. The present study
sought mechanistic explanations for these regulatory changes in heart rate. We
provide evidence for a bicarbonate-activated, soluble adenylyl cyclase (sAC)
dependent mechanism to control heart rate, a mechanism never previously
implicated in chordate cardiac control.
PMID- 27510963
TI - A Description of Vibrational Modes in Hexaphyrins: Understanding the Aromaticity
Reversal in the Lowest Triplet State.
AB - Aromaticity reversal in the lowest triplet state, or Baird's rule, has been
postulated for the past few decades. Despite numerous theoretical works on
aromaticity reversal, experimental study is still at a rudimentary stage. Herein,
we investigate the aromaticity reversal in the lowest excited triplet state using
a comparable set of [26]- and [28]hexaphyrins by femtosecond time-resolved
infrared (IR) spectroscopy. Compared to the relatively simple IR spectra of
[26]bis(rhodium) hexaphyrin (R26H), those of [28]bis(rhodium) hexaphyrin (R28H)
show complex IR spectra the region for the stretching modes of conjugated rings.
Whereas time-resolved IR spectra of R26H in the excited triplet state are
dominated by excited state IR absorption peaks, while those of R28H largely show
ground state IR bleaching peaks, reflecting the aromaticity reversal in the
lowest triplet state. These contrasting IR spectral features serve as new
experimental aromaticity indices for Baird's rule.
PMID- 27510964
TI - Bedside pleuroscopy in Taiwan : a great vision for critically-ill patients and
intensivists.
AB - Bedside pleuroscopy can be used in daily practice by medical pulmonologists if a
patient cannot tolerate either general anesthesia or being moved to an operating
or endoscopy room due to their critical condition. It is a simple and safe
technique that rarely has complications. The aim of this review is to summarize
recent literatures about bedside pleuroscopy and share our experiences with using
it in Taiwan.
PMID- 27510965
TI - Quercetin suppresses cellular migration and invasion in human head and neck
squamous cell carcinoma (HNSCC).
AB - Head and neck squamous cell carcinoma (HNSCC) with aberrant epidermal growth
factor receptor (EGFR) signaling is often associated with a poor prognosis and a
low survival rate. Hence, efficient inhibition of the EGFR signaling-mediated
malignancy would improve survival rate. In a previous study, we demonstrated that
quercetin appears to be a potent anti-tumorigenic agent through its inhibition of
the EGFR/Akt pathway in oral cancer, but its anti-metastatic potential in HNSCC
remains unclear [1]. Here, we have hypothesized that quercetin might be effective
in metastatic inhibition in EGFR-overexpressing HNSCC cells. Quercetin treatment
with 10 MUM (half concentration of IC50) suppressed cell migration and invasion
in EGFR-overexpressing HSC-3 and FaDu HNSCC cells. Quercetin also inhibited the
colony growth of HSC-3 cells embedded in a Matrigel matrix. Among matrix
metalloproteinases (MMPs), the secreted gelatinases MMP-2 and MMP-9 are
responsible for the degradation of gelatin in the extracellular matrix and type
IV collagen in the basement membrane; and this degradation event is crucial for
the migration from the origin and the invasion into the bone in HNSCC. Quercetin
(10 MUM) treatment also suppressed the expression and proteolytic activity of MMP
2 and MMP-9. Taken together, our data indicate that quercetin is an effective
anti-cancer agent against MMP-2- and MMP-9-mediated metastasis in EGFR
overexpressing HNSCC.
PMID- 27510966
TI - Prevalence, awareness, treatment, control of type 2 diabetes mellitus and risk
factors in Chinese rural population: the RuralDiab study.
AB - The study aimed to investigate prevalence, awareness, treatment and control of
type 2 diabetes mellitus (T2DM), and to explore potential risk factors in rural
areas of China. A total of 16413 individuals aged 18-74 years in rural districts
were recruited from the Rural Diabetes, Obesity and Lifestyle (RuralDiab) study
for the epidemiological research. Meanwhile, a meta-analysis including 7
published studies was conducted to validate the result of the cross-sectional
study. The rates of crude and age-standardized prevalence, awareness, treatment
and control of T2DM were 12.19%, 67.00%, 62.35%, 22.20% and 6.98%, 60.11%,
54.85%, 18.77%, respectively. The prevalence, awareness, treatment and control of
T2DM displayed increased trends with age (Ptrend < 0.01) and were strongly
associated with education, drinking, more vegetable and fruit intake, physical
activity, family history of diabetes, body mass index (BMI). The results of this
meta-analysis showed that the pooled prevalence, awareness, treatment and control
of T2DM in China countryside were 7.3% (5.3-9.4%), 57.3% (36.9-77.6%), 48.4%
(32.4-64.5%) and 21.0% (9.9-32.1%), respectively. The prevalence of T2DM was high
with inadequate awareness, treatment and control of T2DM in China rural areas.
Healthy lifestyles should be advocated to reduce prevalence and improve
awareness, treatment, and control of T2DM in Chinese rural residents.
PMID- 27510967
TI - Seed abscission and fruit dehiscence required for seed dispersal rely on similar
genetic networks.
AB - Seed dispersal is an essential trait that enables colonization of new favorable
habitats, ensuring species survival. In plants with dehiscent fruits, such as
Arabidopsis, seed dispersal depends on two processes: the separation of the fruit
valves that protect the seeds (fruit dehiscence) and the detachment of the seeds
from the funiculus connecting them to the mother plant (seed abscission). The key
factors required to establish a proper lignin pattern for fruit dehiscence are
SHATTERPROOF 1 and 2 (SHP1 and SHP2). Here, we demonstrate that the SHP-related
gene SEEDSTICK (STK) is a key factor required to establish the proper lignin
pattern in the seed abscission zone but in an opposite way. We show that STK acts
as a repressor of lignin deposition in the seed abscission zone through the
direct repression of HECATE3, whereas the SHP proteins promote lignin deposition
in the valve margins by activating INDEHISCENT. The interaction of STK with the
SEUSS co-repressor determines the difference in the way STK and SHP proteins
control the lignification patterns. Despite this difference in the molecular
control of lignification during seed abscission and fruit dehiscence, we show
that the genetic networks regulating these two developmental pathways are highly
conserved.
PMID- 27510968
TI - Epb41l5 competes with Delta as a substrate for Mib1 to coordinate specification
and differentiation of neurons.
AB - We identified Erythrocyte membrane protein band 4.1-like 5 (Epb41l5) as a
substrate for the E3 ubiquitin ligase Mind bomb 1 (Mib1), which is essential for
activation of Notch signaling. Although loss of Epb41l5 does not significantly
alter the pattern of neural progenitor cells (NPCs) specified as neurons at the
neural plate stage, it delays their delamination and differentiation after
neurulation when NPCs normally acquire organized apical junctional complexes
(AJCs) in the zebrafish hindbrain. Delays in differentiation are reduced by
knocking down N-cadherin, a manipulation expected to help destabilize adherens
junctions (AJs). This suggested that delays in neuronal differentiation in
epb41l5-deficient embryos are related to a previously described role for Epb41l5
in facilitating disassembly of cadherin-dependent AJCs. Mib1 ubiquitylates
Epb41l5 to promote its degradation. DeltaD can compete with Epb41l5 to reduce
Mib1-dependent Epb41l5 degradation. In this context, increasing the number of
NPCs specified to become neurons, i.e. cells expressing high levels of DeltaD,
stabilizes Epb41l5 in the embryo. Together, these observations suggest that
relatively high levels of Delta stabilize Epb41l5 in NPCs specified as neurons.
This, we suggest, helps coordinate NPC specification with Epb41l5-dependent
delamination and differentiation as neurons.
PMID- 27510969
TI - The Ets protein Pointed prevents both premature differentiation and
dedifferentiation of Drosophila intermediate neural progenitors.
AB - Intermediate neural progenitors (INPs) need to avoid both dedifferentiation and
differentiation during neurogenesis, but the underlying mechanisms are not well
understood. In Drosophila, the Ets protein Pointed P1 (PntP1) is required to
generate INPs from type II neuroblasts. Here, we investigated how PntP1 promotes
INP generation. By generating pntP1-specific mutants and using RNAi knockdown, we
show that the loss of PntP1 leads to both an increase in type II neuroblast
number and the elimination of INPs. The elimination of INPs results from the
premature differentiation of INPs due to ectopic Prospero expression in newly
generated immature INPs (imINPs), whereas the increase in type II neuroblasts
results from the dedifferentiation of imINPs due to loss of Earmuff at later
stages of imINP development. Furthermore, reducing Buttonhead enhances the loss
of INPs in pntP1 mutants, suggesting that PntP1 and Buttonhead act cooperatively
to prevent premature INP differentiation. Our results demonstrate that PntP1
prevents both the premature differentiation and the dedifferentiation of INPs by
regulating the expression of distinct target genes at different stages of imINP
development.
PMID- 27510970
TI - Modeling halotropism: a key role for root tip architecture and reflux loop
remodeling in redistributing auxin.
AB - A key characteristic of plant development is its plasticity in response to
various and dynamically changing environmental conditions. Tropisms contribute to
this flexibility by allowing plant organs to grow from or towards environmental
cues. Halotropism is a recently described tropism in which plant roots bend away
from salt. During halotropism, as in most other tropisms, directional growth is
generated through an asymmetric auxin distribution that generates differences in
growth rate and hence induces bending. Here, we develop a detailed model of auxin
transport in the Arabidopsis root tip and combine this with experiments to
investigate the processes generating auxin asymmetry during halotropism. Our
model points to the key role of root tip architecture in allowing the decrease in
PIN2 at the salt-exposed side of the root to result in a re-routing of auxin to
the opposite side. In addition, our model demonstrates how feedback of auxin on
the auxin transporter AUX1 amplifies this auxin asymmetry, while a salt-induced
transient increase in PIN1 levels increases the speed at which this occurs. Using
AUX1-GFP imaging and pin1 mutants, we experimentally confirmed these model
predictions, thus expanding our knowledge of the cellular basis of halotropism.
PMID- 27510971
TI - Quiescent center initiation in the Arabidopsis lateral root primordia is
dependent on the SCARECROW transcription factor.
AB - Lateral root formation is an important determinant of root system architecture.
In Arabidopsis, lateral roots originate from pericycle cells, which undergo a
program of morphogenesis to generate a new lateral root meristem. Despite its
importance for root meristem organization, the onset of quiescent center (QC)
formation during lateral root morphogenesis remains unclear. Here, we used live
3D confocal imaging to monitor cell organization and identity acquisition during
lateral root development. Our dynamic observations revealed an early
morphogenesis phase and a late meristem formation phase as proposed in the bi
phasic growth model. Establishment of lateral root QCs coincided with this
developmental phase transition. QC precursor cells originated from the outer
layer of stage II lateral root primordia, within which the SCARECROW (SCR)
transcription factor was specifically expressed. Disrupting SCR function
abolished periclinal divisions in this lateral root primordia cell layer and
perturbed the formation of QC precursor cells. We conclude that de novo QC
establishment in lateral root primordia operates via SCR-mediated formative cell
division and coincides with the developmental phase transition.
PMID- 27510973
TI - Control of germline stem cell differentiation by Polycomb and Trithorax group
genes in the niche microenvironment.
AB - Polycomb and Trithorax group (PcG and TrxG) genes function to regulate gene
transcription by maintaining a repressive or active chromatin state,
respectively. This antagonistic activity is important for body patterning during
embryonic development, but whether this function module has a role in adult
tissues is unclear. Here, we report that in the Drosophila ovary, disruption of
the Polycomb repressive complex 1 (PRC1), specifically in the supporting escort
cells, causes blockage of cystoblast differentiation and germline stem cell-like
tumor formation. Tumors are caused by derepression of decapentaplegic (dpp),
which prevents cystoblast differentiation. Interestingly, activation of dpp in
escort cells requires the function of the TrxG gene brahma (brm), suggesting that
loss of PRC1 in escort cells causes Brm-dependent dpp expression. Our study
suggests a requirement for balanced activity between PcG and TrxG in an adult
stem cell niche, and disruption of this balance could lead to the loss of tissue
homeostasis and tumorigenesis.
PMID- 27510972
TI - A novel small molecule that disrupts a key event during the oocyte-to-embryo
transition in C. elegans.
AB - The complex cellular events that occur in response to fertilization are essential
for mediating the oocyte-to-embryo transition. Here, we describe a comprehensive
small-molecule screen focused on identifying compounds that affect early
embryonic events in Caenorhabditis elegans We identify a single novel compound
that disrupts early embryogenesis with remarkable stage and species specificity.
The compound, named C22, primarily impairs eggshell integrity, leading to osmotic
sensitivity and embryonic lethality. The C22-induced phenotype is dependent upon
the upregulation of the LET-607/CREBH transcription factor and its candidate
target genes, which primarily encode factors involved in diverse aspects of
protein trafficking. Together, our data suggest that in the presence of C22, one
or more key components of the eggshell are inappropriately processed, leading to
permeable, inviable embryos. The remarkable specificity and reversibility of this
compound will facilitate further investigation into the role and regulation of
protein trafficking in the early embryo, as well as serve as a tool for
manipulating the life cycle for other studies such as those involving aging.
PMID- 27510974
TI - Plastid osmotic stress influences cell differentiation at the plant shoot apex.
AB - The balance between proliferation and differentiation in the plant shoot apical
meristem is controlled by regulatory loops involving the phytohormone cytokinin
and stem cell identity genes. Concurrently, cellular differentiation in the
developing shoot is coordinated with the environmental and developmental status
of plastids within those cells. Here, we employ an Arabidopsis thaliana mutant
exhibiting constitutive plastid osmotic stress to investigate the molecular and
genetic pathways connecting plastid osmotic stress with cell differentiation at
the shoot apex. msl2 msl3 mutants exhibit dramatically enlarged and deformed
plastids in the shoot apical meristem, and develop a mass of callus tissue at the
shoot apex. Callus production in this mutant requires the cytokinin receptor AHK2
and is characterized by increased cytokinin levels, downregulation of cytokinin
signaling inhibitors ARR7 and ARR15, and induction of the stem cell identity gene
WUSCHEL Furthermore, plastid stress-induced apical callus production requires
elevated plastidic reactive oxygen species, ABA biosynthesis, the retrograde
signaling protein GUN1, and ABI4. These results are consistent with a model
wherein the cytokinin/WUS pathway and retrograde signaling control cell
differentiation at the shoot apex.
PMID- 27510975
TI - Minibrain drives the Dacapo-dependent cell cycle exit of neurons in the
Drosophila brain by promoting asense and prospero expression.
AB - A key aim of neurodevelopmental research is to understand how precursor cells
decide to stop dividing and commence their terminal differentiation at the
correct time and place. Here, we show that minibrain (mnb), the Drosophila
ortholog of the Down syndrome candidate gene DYRK1A, is transiently expressed in
newborn neuronal precursors known as ganglion cells (GCs). Mnb promotes the cell
cycle exit of GCs through a dual mechanism that regulates the expression of the
cyclin-dependent kinase inhibitor Dacapo, the homolog of vertebrate p27(Kip1)
(Cdkn1b). Mnb upregulates the expression of the proneural transcription factor
(TF) Asense, which promotes Dacapo expression. Mnb also induces the expression of
Prospero, a homeodomain TF that in turn inhibits the expression of Deadpan, a pan
neural TF that represses dacapo In addition to its effects on Asense and
Prospero, Mnb also promotes the expression of the neuronal-specific RNA regulator
Elav, strongly suggesting that Mnb facilitates neuronal differentiation. These
actions of Mnb ensure the precise timing of neuronal birth, coupling the
mechanisms that regulate neurogenesis, cell cycle control and terminal
differentiation of neurons.
PMID- 27510976
TI - A role for post-transcriptional control of endoplasmic reticulum dynamics and
function in C. elegans germline stem cell maintenance.
AB - Membrane-bound receptors, which are crucial for mediating several key
developmental signals, are synthesized on endoplasmic reticulum (ER). The
functional integrity of ER must therefore be important for the regulation of at
least some developmental programs. However, the developmental control of ER
function is not well understood. Here, we identify the C. elegans protein FARL
11, an ortholog of the mammalian STRIPAK complex component STRIP1/2 (FAM40A/B),
as an ER protein. In the C. elegans embryo, we find that FARL-11 is essential for
the cell cycle-dependent morphological changes of ER and for embryonic viability.
In the germline, FARL-11 is required for normal ER morphology and for membrane
localization of the GLP-1/Notch receptor involved in germline stem cell (GSC)
maintenance. Furthermore, we provide evidence that PUF-8, a key translational
regulator in the germline, promotes the translation of farl-11 mRNA. These
findings reveal that ER form and function in the C. elegans germline are post
transcriptionally regulated and essential for the niche-GSC signaling mediated by
GLP-1.
PMID- 27510977
TI - Brg1 plays an essential role in development and homeostasis of the duodenum
through regulation of Notch signaling.
AB - Brg1, a core subunit of the SWI/SNF chromatin remodeling complex, is essential
for development and homeostasis of various organs. However, the functional role
of Brg1 in intestinal development and homeostasis, and the underlying molecular
mechanism, remain unknown. We found that deletion of Brg1 in the mouse intestine
resulted in growth impairment and early death associated with abnormal crypt
villous formation, skewed differentiation into secretory lineage cells, markedly
increased apoptosis, and stem cell loss in the duodenum. Furthermore, we found
that the Notch signaling pathway was dramatically downregulated in Brg1-deficient
duodenum. Remarkably, overexpression of the Notch1 intercellular domain (ICD)
partially reversed the prognosis of intestinal Brg1 mutant mice. Notch1 ICD
overexpression rescued morphogenesis, prevented over-differentiation into
secretory lineage cells, and restored apoptosis to normal levels in Brg1
deficient duodenum, although stem cell loss was not rescued. Our data demonstrate
that Brg1 plays an essential role in development and homeostasis, including
morphogenesis, stem cell differentiation and cell survival in the duodenum.
Mechanistically, the rescue of the intestinal Brg1 mutant phenotype by
overexpression of the Notch1 ICD indicates that Notch signaling is a key
downstream target that mediates the effects of Brg1.
PMID- 27510978
TI - Eye development and photoreceptor differentiation in the cephalopod Doryteuthis
pealeii.
AB - Photoreception is a ubiquitous sensory ability found across the Metazoa, and
photoreceptive organs are intricate and diverse in their structure. Although the
morphology of the compound eye in Drosophila and the single-chambered eye in
vertebrates have elaborated independently, the amount of conservation within the
'eye' gene regulatory network remains controversial, with few taxa studied. To
better understand the evolution of photoreceptive organs, we established the
cephalopod Doryteuthis pealeii as a lophotrochozoan model for eye development.
Utilizing histological, transcriptomic and molecular assays, we characterize eye
formation in Doryteuthis pealeii Through lineage tracing and gene expression
analyses, we demonstrate that cells expressing Pax and Six genes incorporate into
the lens, cornea and iris, and the eye placode is the sole source of retinal
tissue. Functional assays demonstrate that Notch signaling is required for
photoreceptor cell differentiation and retinal organization. This comparative
approach places the canon of eye research in traditional models into perspective,
highlighting complexity as a result of both conserved and convergent mechanisms.
PMID- 27510979
TI - Identification and characterization of thermostable glucose dehydrogenases from
thermophilic filamentous fungi.
AB - FAD-dependent glucose dehydrogenase (FAD-GDH), which contains FAD as a cofactor,
catalyzes the oxidation of D-glucose to D-glucono-1,5-lactone, and plays an
important role in biosensors measuring blood glucose levels. In order to obtain a
novel FAD-GDH gene homolog, we performed degenerate PCR screening of genomic DNAs
from 17 species of thermophilic filamentous fungi. Two FAD-GDH gene homologs were
identified and cloned from Talaromyces emersonii NBRC 31232 and Thermoascus
crustaceus NBRC 9129. We then prepared the recombinant enzymes produced by
Escherichia coli and Pichia pastoris. Absorption spectra and enzymatic assays
revealed that the resulting enzymes contained oxidized FAD as a cofactor and
exhibited glucose dehydrogenase activity. The transition midpoint temperatures (T
m) were 66.4 and 62.5 degrees C for glycosylated FAD-GDHs of T. emersonii and T.
crustaceus prepared by using P. pastoris as a host, respectively. Therefore, both
FAD-GDHs exhibited high thermostability. In conclusion, we propose that these
thermostable FAD-GDHs could be ideal enzymes for use as thermotolerant glucose
sensors with high accuracy.
PMID- 27510980
TI - Effect of air-blast drying and the presence of protectants on the viability of
yeast entrapped in calcium alginate beads with an aim to improve the survival
rate.
AB - Five yeast strains, Saccharomyces cerevisiae D8, M12, and S13; Hanseniaspora
uvarum S6; and Issatchenkia orientalis KMBL5774, isolated from Korean grapes,
were entrapped in Ca-alginate beads, which are non-toxic, simple to use, and
economical. Ca-alginate beads containing yeast cells were soaked in protective
solutions, such as skim milk, saccharides, polyols, and nitrogen compounds,
before air-blast drying to improve the yeast survival rate and storage ability.
The results showed that both entrapment in Ca-alginate beads and soaking in
protective agents favorably affected the survival of all strains. The
microenvironment formed by the beads and protective agents can protect the yeast
cells from harsh environmental conditions, such as low water (below 10 %). All
the yeast strains entrapped in Ca-alginate beads showed greater than 80 %
survival and less than 11 % water content after air-blast drying at 37 degrees C
for 5 h. In addition, air-blast dried cells of S. cerevisiae D8, M12, S13; H.
uvarum S6; and I. orientalis KMBL5774 entrapped in 2 % Ca-alginate beads and
soaked in protective agents (10 % skim milk containing 10 % sucrose, 10 %
raffinose, 10 % trehalose, 10 % trehalose, and 10 % glucose, respectively) after
air-blast drying at 37 degrees C for 5 h showed 90, 87, 92, 90, and 87 %
viability, respectively. All dried entrapped yeast cells showed survival rates of
at least 51 % after storage at 4 degrees C for 3 months.
PMID- 27510981
TI - SOS gene induction and possible mutagenic effects of freeze-drying in Escherichia
coli and Salmonella typhimurium.
AB - We report the results of a study of the potential negative effects of the freeze
drying process, normally considered a benign means for long-term conservation of
living cells and the golden standard in bacterial preservation. By monitoring
gene induction using a whole-cell Escherichia coli bioreporter panel, in which
diverse stress-responsive gene promoters are fused to luminescent or fluorescent
reporting systems, we have demonstrated that DNA repair genes belonging to the
SOS operon (recA, sulA, uvrA, umuD, and lexA) were induced upon resuscitation
from the freeze-dried state, whereas other stress-responsive promoters such as
grpE, katG, phoA, soxS, and sodA were not affected. This observation was
confirmed by the UMU-chromotest (activation of the umuD gene promoter) in
Salmonella typhimurium, as well as by real-time PCR analyses of selected E. coli
SOS genes. We further show that a functional SOS operon is important in viability
maintenance following resuscitation, but that at the same time, this repair
system may introduce significantly higher mutation rates, comparable to those
induced by high concentrations of a known mutagen. Our results also indicate that
the entire freeze-drying process, rather than either freezing or drying
separately, is instrumental in the induction of DNA damage.
PMID- 27510983
TI - WOMEN'S EMPOWERMENT, HOUSEHOLD STATUS AND CONTRACEPTION USE IN GHANA.
AB - Gender inequality is often cited as a barrier to improving women's sexual and
reproductive health outcomes, including contraceptive use, in low- and middle
income countries such as those in sub-Saharan Africa. To date there is limited,
recent, evidence available regarding women's empowerment, household status and
contraceptive use in Ghana. The objective of this study was to investigate
whether women's empowerment and status in the household were associated with
contraceptive use and unmet need for contraception using the 2014 Ghana
Demographic and Health Survey. The study sample consisted of 1828 women aged 15
49. Women's empowerment was measured based on two composite indexes created by
the DHS: attitudes towards intimate partner violence and decision-making. Women's
status in the home was measured using indicators of work status, relationship to
household head, control over monetary earnings and land ownership. Decision
making was found to be positively associated with contraceptive use and not
having unmet need for contraception. Women who justified wife beating in one or
more instances were less likely to use contraception, and more likely to have
unmet need for contraception. Current or past employment and higher levels of
male partner education were associated with contraceptive use. This study
indicates that women's empowerment and household status are influential for
contraceptive indicators. Future interventions aimed at improving contraceptive
uptake and use should promote women's empowerment, i.e. decision-making, self
worth and education.
PMID- 27510982
TI - Impact of quercetin-induced changes in drug-metabolizing enzyme and transporter
expression on the pharmacokinetics of cyclosporine in rats.
AB - The aim of the present study was to evaluate whether quercetin (Que) modulates
the mRNA and protein expression levels of drug-metabolizing enzymes (DMEs) and
drug transporters (DTs) in the small intestine and liver, and thus modifies the
pharmacokinetic profile of cyclosporine (CsA) in rats. This two-part study
evaluated the pharmacokinetic profiles of CsA in the presence or absence of Que
(experiment I) and the involvement of DMEs and DTs (experiment II). In experiment
I, 24 rats received single-dose CsA (10 mg/kg) on day 1, single-dose Que (25, 50
and 100 mg/kg/day; eight rats in each group) on days 3-8, and concomitant CsA/Que
on day 9. In experiment II, the mRNA and protein expression levels of cytochrome
P (CYP)3A1, CYP3A2, UDP glucuronosyltransferase family 1 member A complex locus,
organic anion-transporting polypeptide (OATP)2B1, OATP1B2, P-glycoprotein, breast
cancer resistance protein, and multidrug resistance-associated protein 2 in the
small intestine and liver of rats were analyzed following oral administration of
Que at 25, 50 and 100 mg/kg in the presence or absence of CsA (10 mg/kg) for
seven consecutive days. Co-administration of Que (25,50 and 100 mg/kg) decreased
the maximum serum concentration of CsA by 46, 50 and 47% in a dose-independent
manner. In addition, the area under the curve to the last measurable
concentration and area under the curve to infinite time were decreased, by 21 and
16%, 30 and 33%, and 33 and 34% (P<0.01), respectively. However, the mRNA and
protein expression levels of the above-mentioned DMEs and DTs were inhibited by
Que in a dose-dependent manner (P<0.01) to a similar extent in the small
intestine and liver. It was demonstrated that Que was able to reduce the
bioavailability of CsA following multiple concomitant doses in rats. Overlapping
modulation of intestinal and hepatic DMEs and DTs, as well as the DME-DT
interplay are potential explanations for these observations.
PMID- 27510984
TI - Bimetallic salen aluminum complexes: cooperation between reactive centers in the
ring-opening polymerization of lactides and epoxides.
AB - Three dinuclear aluminum alkyl complexes of the general formula LAl2Me4, where L
are salen ligands with an alkyl backbone of different lengths between the
nitrogen atoms (1,3-propylene (1), 1,5-pentylene (2) and 1,12-dodecaylene (3)),
have been prepared through alkane elimination reactions between each ligand and
two equivalents of AlMe3. The related hemi-salen aluminum complex 4 was prepared
by an analogous reaction between a phenoxy-imine ligand and a single equivalent
of AlMe3. The activities of these aluminum complexes in the ring-opening
polymerization (ROP) of rac-lactide and of several epoxides have been
investigated and compared. The dinuclear complex 1, bearing the salen ligand with
the shortest alkyl bridge, was the most active in the ROP of LA producing
isotactic enriched PLA. Otherwise, the other complexes (2 and 3), in which the
metal centers are remote, produced atactic PLA with inferior activity. Analogous
differences in terms of activity emerged in the ROP of epoxides. The comparison
of the catalytic behavior of the dinuclear complexes as well as their mononuclear
counterparts suggests the cooperation between the two aluminum metal centers of
the dinuclear species in which these are close enough.
PMID- 27510985
TI - Effect of hesperidin on the pharmacokinetics of CPT-11 and its active metabolite
SN-38 by regulating hepatic Mrp2 in rats.
AB - The usage of irinotecan hydrochloride (CPT-11) chemotherapy is hindered by its
dose-limiting diarrhea which appears to be associated with the intestinal
exposure to SN-38, the active metabolite of CPT-11. Hesperidin, a safe and
natural food ingredient flavonoid, exhibits various biological properties.
Accumulated evidence showed that the regulatory effect of hesperidin on the
expression of Mrp2 in the liver may be one of the critical factors controlling
the biliary excretion of SN-38. This study examined the effect of hesperidin on
the pharmacokinetics of CPT-11 and SN-38 as well as the regulatory effect on the
hepatic expression of Mrp2. Compared with the control group, the AUC5-t was
increased to 115% of CPT-11 and 122% of SN-38; the CL was decreased to 87% for
CPT-11; the tissue concentration was increased in the liver, kidney and colon;
and the accumulated biliary excretion was significantly decreased to 77% for CPT
11 and 76% for SN-38 in hesperidin-treated rats. Furthermore, the expression of
Mrp2 in the liver was significantly decreased to 37% in the hesperidin-treated
rats compared with that of the control group. These results indicate that oral
administration of hesperidin significantly increased the AUC5-t and reduced the
clearance of CPT-11 and SN-38, possibly by decreasing the hepatic expression of
Mrp2, and thus inhibiting the biliary excretion of CPT-11 and SN-38. The results
from this present study suggest that hesperidin may reduce the exposure of CPT-11
and SN-38 in the intestine by reducing the amount of biliary excretion of CPT-11
and SN-38. Copyright (c) 2016 John Wiley & Sons, Ltd.
PMID- 27510986
TI - Assessment of the spatial variability in tall wheatgrass forage using LANDSAT 8
satellite imagery to delineate potential management zones.
AB - Little information is available on the degree of within-field variability of
potential production of Tall wheatgrass (Thinopyrum ponticum) forage under
unirrigated conditions. The aim of this study was to characterize the spatial
variability of the accumulated biomass (AB) without nutritional limitations
through vegetation indexes, and then use this information to determine potential
management zones. A 27-*-27-m grid cell size was chosen and 84 biomass sampling
areas (BSA), each 2 m(2) in size, were georeferenced. Nitrogen and phosphorus
fertilizers were applied after an initial cut at 3 cm height. At 500 degrees C
day, the AB from each sampling area, was collected and evaluated. The spatial
variability of AB was estimated more accurately using the Normalized Difference
Vegetation Index (NDVI), calculated from LANDSAT 8 images obtained on 24 November
2014 (NDVInov) and 10 December 2014 (NDVIdec) because the potential AB was highly
associated with NDVInov and NDVIdec (r (2) = 0.85 and 0.83, respectively). These
models between the potential AB data and NDVI were evaluated by root mean squared
error (RMSE) and relative root mean squared error (RRMSE). This last coefficient
was 12 and 15 % for NDVInov and NDVIdec, respectively. Potential AB and NDVI
spatial correlation were quantified with semivariograms. The spatial dependence
of AB was low. Six classes of NDVI were analyzed for comparison, and two
management zones (MZ) were established with them. In order to evaluate if the
NDVI method allows us to delimit MZ with different attainable yields, the AB
estimated for these MZ were compared through an ANOVA test. The potential AB had
significant differences among MZ. Based on these findings, it can be concluded
that NDVI obtained from LANDSAT 8 images can be reliably used for creating MZ in
soils under permanent pastures dominated by Tall wheatgrass.
PMID- 27510987
TI - Microthymoma in elderly-onset myasthenia gravis detected preoperatively.
AB - A 77-year-old woman with a 3-month history of muscle weakness was diagnosed with
elderly-onset generalized myasthenia gravis (Myasthenia Gravis Foundation of
America classification IIa) based on a high serum acetylcholine receptor antibody
level (25.4 nmol.L-1) and neurological findings. Computed tomography detected a
small nodule (diameter 15 mm) in the anterior mediastinum, which was suspected to
be a thymoma. An extended thymectomy was performed. The pathological examination
revealed a 6-mm-diameter thymoma, termed a microthymoma, accompanied with a
unilocular thymic cyst without capsule formation (type B2 according to the World
Health Organization classification). Some fat tissue was also found within the
tumor.
PMID- 27510988
TI - Stand up for the NHS: Margaret McCartney joins Phil Hammond on stage in
Edinburgh.
PMID- 27510989
TI - Local environment of metal ions in phthalocyanines: K-edge X-ray absorption
spectra.
AB - We report a detailed study of the K-edge X-ray absorption spectra of four
transition metal phthalocyanines (MPc, M = Fe, Co, Cu and Zn). We identify the
important single and multiple scattering contributions to the spectra in the
extended energy range and provide a robust treatment of thermal damping; thus, a
generally applicable model for the interpretation of X-ray absorption fine
structure spectra is proposed. Consistent variations of bond lengths and Debye
Waller factors are found as a function of atomic number of the metal ion,
indicating a variation of the metal-ligand bond strength which correlates with
the spatial arrangement and occupation of molecular orbitals. We also provide an
interpretation of the near edge spectral features in the framework of a full
potential real space multiple scattering approach and provide a connection to the
local electronic structure.
PMID- 27510990
TI - Impaired Ca(2+) release contributes to muscle weakness in a rat model of critical
illness myopathy.
AB - BACKGROUND: Critical illness myopathy is an acquired skeletal muscle disorder
with severe myosin loss and muscle weakness frequently seen in intensive care
unit (ICU) patients. It is unknown if impaired excitation-contraction coupling
contributes to the muscle weakness. METHODS: We used a unique ICU model where
rats were deeply sedated, post-synaptically pharmacologically paralyzed,
mechanically ventilated and closely monitored for up to ten days. Single intact
fibers from the flexor digitorum brevis muscle were isolated and used to measure
force and free myoplasmic [Ca(2+)] ([Ca(2+)]i) during tetanic contractions.
RESULTS: Fibers from ICU rats had 80 % lower tetanic [Ca(2+)]i and produced only
15 % of the force seen in fibers from sham-operated (SHAM) rats. In the presence
of 5 mM caffeine, tetanic [Ca(2+)]i was similar in fibers from ICU and SHAM rats
but force was 50 % lower in fibers from ICU rats than SHAM rats. Confocal imaging
showed disrupted tetanic [Ca(2+)]i transients in fibers from ICU rats compared to
SHAM rats. Western blots showed similar levels of Na(+) channel and
dihydropyridine receptor (DHPR) protein expression, whereas ryanodine receptor
(RyR) and sarco-endoplasmic reticulum Ca(2+) ATPase 1 (SERCA1) expression was
markedly lower in muscle of ICU rats than in SHAM rats. Immunohistochemical
analysis showed that distribution of Na(+) channel and DHPR protein on the
sarcolemma was disrupted in fibers from ICU rats compared with SHAM rats.
CONCLUSIONS: These results suggest that impaired SR Ca(2+) release contributes to
the muscle weakness seen in patients in ICU.
PMID- 27510991
TI - Dysregulated immune system networks in war veterans with PTSD is an outcome of
altered miRNA expression and DNA methylation.
AB - Post-traumatic stress disorder patients experience chronic systemic inflammation.
However, the molecular pathways involved and mechanisms regulating the expression
of genes involved in inflammatory pathways in PTSD are reported inadequately.
Through RNA sequencing and miRNA microarray, we identified 326 genes and 190
miRNAs that were significantly different in their expression levels in the PBMCs
of PTSD patients. Expression pairing of the differentially expressed genes and
miRNAs indicated an inverse relationship in their expression. Functional analysis
of the differentially expressed genes indicated their involvement in the
canonical pathways specific to immune system biology. DNA methylation analysis of
differentially expressed genes also showed a gradual trend towards differences
between control and PTSD patients, again indicating a possible role of this
epigenetic mechanism in PTSD inflammation. Overall, combining data from the three
techniques provided a holistic view of several pathways in which the
differentially expressed genes were impacted through epigenetic mechanisms, in
PTSD. Thus, analysis combining data from RNA-Seq, miRNA array and DNA
methylation, can provide key evidence about dysregulated pathways and the
controlling mechanism in PTSD. Most importantly, the present study provides
further evidence that inflammation in PTSD could be epigenetically regulated.
PMID- 27510992
TI - Reduction of Hexavalent Chromium by Green Tea Polyphenols and Green Tea Nano Zero
Valent Iron (GT-nZVI).
AB - This study reports on the direct reduction of hexavalent chromium [Cr(VI)] by
green tea polyphenols, including a green tea solution and pure epigallocatechin
gallate (EGCG) solution. A linear trend was observed between the amount of
reduced Cr(VI) and the amount of added polyphenols. The green tea solution showed
a continued decrease in the observed stoichiometry with increasing pH, from a
maximum of 1.4 mol per gallic acid equivalent (GAE) of green tea at pH 2.5, to
0.2 mol/GAE at pH 8.8. The EGCG solution exhibited different behavior, with a
maximum stoichiometry of 2 at pH 7 and minimum of 1.6 at pH 4.4 and 8.9. When
green tea was used to first react with Fe3+ and form GT-nZVI, the amount of
Cr(VI) reduced by a certain volume of GT-nZVI was double compared to green tea,
and 6 times as high considering that GT-nZVI only contains 33 % green tea.
PMID- 27510993
TI - A Review of Organophosphate Esters in the Environment from Biological Effects to
Distribution and Fate.
AB - Organophosphate esters (OPEs) are synthetic phosphoric acid derivatives used in a
wide variety of applications including as flame retardants and plasticizers.
Their production and usage has increased in recent years, due to the phase-out of
other flame retardant formulations (e.g., polybrominated diphenyl ethers). As
such, there has been a recent push to understand the global distribution of OPEs
and their behaviour in biota. Multiple studies have been published over the last
few years pertaining to OPE concentrations in biotic and abiotic environmental
compartments, as well as the metabolism of OPEs in biota. This paper aims to
provide a brief review of the occurrence and levels of OPEs in the environment,
as well as recent developments concerning the elucidation of OPE metabolism in
biota.
PMID- 27510994
TI - Assessing the Effects of Amoxicillin on Antioxidant Enzyme Activities, Lipid
Peroxidation and Protein Carbonyl Content in the Clam Ruditapes philippinarum and
the Mussel Mytilus galloprovincialis.
AB - In this study, we evaluated the capability of amoxicillin (AMX)-one of the most
widely used antibiotics worldwide-to induce oxidative stress in both gills and
digestive gland from two bivalve species, the clam Ruditapes philippinarum and
the mussel Mytilus galloprovincialis. Superoxide dismutase (SOD) and catalase
(CAT) activities, as well as the lipid peroxidation levels (LPO) and protein
carbonyl content (PCC), were measured in bivalves exposed to 100, 200 and 400 ug
AMX/L for 1, 3 and 7 days. The results obtained demonstrated that AMX affected
slightly biomarker responses of molluscs.
PMID- 27510995
TI - The Road to Resilience: Insights on Training Community Coalitions in the Los
Angeles County Community Disaster Resilience Project.
AB - OBJECTIVE: Local health departments (LHDs) have little guidance for
operationalizing community resilience (CR). We explored how community coalitions
responded to 4 CR levers (education, engagement, partnerships, and community self
sufficiency) during the first planning year of the Los Angeles County Community
Disaster Resilience (LACCDR) Project. METHODS: Sixteen communities were selected
and randomly assigned to the experimental CR group or the control preparedness
group. Eight CR coalitions met monthly to plan CR-building activities or to
receive CR training from a public health nurse. Trained observers documented the
coalitions' understanding and application of CR at each meeting. Qualitative
content analysis was used to analyze structured observation reports around the 4
levers. RESULTS: Analysis of 41 reports suggested that coalitions underwent a
process of learning about and applying CR concepts in the planning year. Groups
resonated with ideas of education, community self-sufficiency, and engagement,
but increasing partnerships was challenging. CONCLUSIONS: LHDs can support
coalitions by anticipating the time necessary to understand CR and by
facilitating engagement. Understanding the issues that emerge in the early phases
of planning and implementing CR-building activities is critical. LHDs can use the
experience of the LACCDR Project's planning year as a guide to navigate
challenges and issues that emerge as they operationalize the CR model. (Disaster
Med Public Health Preparedness. 2016;10:812-821).
PMID- 27510996
TI - [Autologous stem cell transplantation in systemic sclerosis].
AB - Autologous hematopoietic stem cell transplantation (HSCT) is a very effective
treatment option for patients with severe systemic sclerosis (SSc). In addition
to various case series two randomized controlled trials could prove its
superiority over intense cyclophosphamide pulse therapy. Nevertheless, HSCT is
associated with a treatment-related mortality of approximately 10 %; therefore,
further studies should be carried out to reduce the toxicity of HSCT by
adaptation of the therapy regimen and the option of HSCT should be made available
earlier to patients with a high risk of mortality. The mechanism of action of
HSCT is still poorly understood. While profibrotic cytokines or even
autoantibodies hardly appear to be influenced by the treatment, alterations to
regulatory T-cells may play a role. Further improvement of transplantation
regimens as well as a better understanding of the underlying pathogenetic
principles and mechanisms of action should be the aim of further studies on HSCT.
PMID- 27510998
TI - Nocardia lasii sp. nov., a novel actinomycete isolated from the cuticle of an ant
(Lasius fuliginosus L).
AB - A novel actinomycete, designated strain 3C-HV12T, was isolated from the cuticle
of an ant (Lasius fuliginosus L) and characterised using a polyphasic approach.
16S rRNA gene sequence similarity studies showed that strain 3C-HV12T belongs to
the genus Nocardia with high sequence similarities to Nocardia soli DSM 44488T
(99.2 %) and Nocardia cummidelens R89T (99.2 %), and phylogenetically clustered
with these two species and Nocardia ignorata DSM 44496T (98.8 %), Nocardia
salmonicida JCM 4826T (98.8 %), Nocardia fluminea S1T (98.8 %), Nocardia coubleae
OFN N12T (98 %) and Nocardia camponoti 1H-HV4T (97.4 %). The morphological and
chemotaxonomic properties of the strain are also consistent with those of members
of the genus Nocardia. The strain was observed to form extensively branched
substrate hyphae which fragmented into rod-shaped and non-motile elements. The
cell wall was found to contain meso-diaminopimelic acid and the whole cell sugars
were identified as arabinose and galactose. The predominant menaquinone was
identified as MK-8(H4, omega-cycl). The phospholipid profile was found to consist
of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and
phosphatidylinositol mannoside. The major fatty acids were identified as C18:0 10
methyl, C16:0 and C16:1omega7c. Mycolic acids were found to be present. A
combination of DNA-DNA hybridisation experiments and phenotypic tests were
carried out between strain 3C-HV12T and its phylogenetically closely related
strains, which further clarified their relatedness and demonstrated that 3C-HV12T
could be distinguished from these strains. Therefore, the strain is concluded to
represent a novel species of the genus Nocardia, for which the name Nocardia
lasii sp. nov. is proposed. The type strain is 3C-HV12T (=DSM 100525T = CGMCC
4.7279T).
PMID- 27510997
TI - Transglutaminase 2 in cartilage homoeostasis: novel links with inflammatory
osteoarthritis.
AB - Transglutaminase 2 (TG2) is highly expressed during chondrocyte maturation and
contributes to the formation of a mineralised scaffold by introducing crosslinks
between extracellular matrix (ECM) proteins. In healthy cartilage, TG2 stabilises
integrity of ECM and likely influences cartilage stiffness and mechanistic
properties. At the same time, the abnormal accumulation of TG2 in the ECM
promotes chondrocyte hypertrophy and cartilage calcification, which might be an
important aspect of osteoarthritis (OA) initiation. Although excessive joint
loading and injuries are one of the main causes leading to OA development, it is
now being recognised that the presence of inflammatory mediators accelerates OA
progression. Inflammatory signalling is known to stimulate the extracellular TG2
activity in cartilage and promote TG2-catalysed crosslinking of molecules that
promote chondrocyte osteoarthritic differentiation. It is, however, unclear
whether TG2 activity aims to resolve or aggravate damages within the arthritic
joint. Better understanding of the complex signalling pathways linking
inflammation with TG2 activities is needed to identify the role of TG2 in OA and
to define possible avenues for therapeutic interventions.
PMID- 27510999
TI - Establishment and gene expression analysis of disease-derived induced pluripotent
stem cells of scleroderma.
AB - BACKGROUND: We recently generated induced pluripotent stem cells (iPSCs) from
cultured dermal fibroblasts of systemic sclerosis (SSc-iPSC) to study the disease
mechanisms. OBJECTIVE: In the present study, we have performed gene expression
analysis using cultured SSc dermal fibroblasts, SSc-iPSC, and fibroblasts re
differentiated from SSc-iPSC (SSc-iPSC-FB). METHODS: mRNA and protein levels of
collagen and integrins were analyzed using PCR array, PCR, immunoblotting, and
immunofluorescence. RESULTS: We compared expression pattern of TGF-beta-related
genes between normal iPSC (NS-iPSC) and SSc-iPSC by PCR array, and found
constitutive and significant down-regulation of S100A8, Smad6, and TGF-beta2 in
SSc-iPSC. The expression of these genes was not altered in cultured SSc
fibroblasts or SSc-iPSC-FB compared to NS fibroblasts or NS-iPSC-FB,
respectively. On the other hand, the expression of collagen, integrin alpha and
beta was up-regulated in SSc fibroblasts, while SSc-iPSC-FB showed normalized
levels of collagen and integrin beta. CONCLUSIONS: So far, there have been no
reports investigating disease-derived iPSCs of SSc. Our results suggest that
S100A8, Smad6, and TGF-beta2 may be the key molecules of this disease. On the
other hand, the normalization of collagen and integrins by iPSC reprogramming
suggests that epigenetic modifications of genes may play a role in the mechanism
of collagen accumulation seen in SSc fibroblasts, and that gene reprogramming may
become novel therapeutic approach. As the limitation of this study, we
established only one iPSC line from each patient, which may not be enough to
discuss disease-specific phenotypes. Larger studies including increased number of
iPSC lines are needed in the future.
PMID- 27511000
TI - Cancer symptom scale preferences: does one size fit all?
AB - OBJECTIVES: Patients with advanced cancer do not report all symptoms, so
assessment is best done systematically. However, for such patients, completion
rates of some symptom instruments are <50%. Symptoms can be quantified by various
scales including the Categorical Response Scale (CRS), Numerical Rating Scale
(NRS) and Visual Analogue Scale (VAS). Patient preferences for CRS, NRS and VAS
in symptom assessment and their clinical utility in 3 cancer symptoms: pain,
tiredness and appetite loss were determined. METHODS: A prospective survey was
conducted involving cancer admissions to a 36-bed palliative care unit. RESULTS:
100 inpatients were recruited, aged 38-93 years (x =71 years; SD=11.6), with
median Eastern Cooperative Oncology Group (ECOG) scores of 2 (range 0-4). VAS was
the least preferred measure. 52% of patients choose the same scale for all 3
symptoms and 44% for 2, with 4% choosing a different individual scale per
symptom. There was moderate agreement between participant scale preference and
observer determined ease of scale completion (loss of appetite: kappa=0.36; pain:
kappa=0.49; tiredness: kappa=0.45). Participants preferred CRS for appetite loss
(48%) and tiredness (40%) and NRS for pain (44%). CONCLUSIONS: VAS was the least
favoured scale and should be used cautiously in this population. Most
participants had a scale preference with high intrapatient consistency between
scales. CRS was preferred for appetite loss and tiredness and NRS for pain.
Consideration should be given to individualised cancer symptom assessment
according to patient scale preference.
PMID- 27511001
TI - Evaluating the experiences and support needs of people living with chronic
cancer: development and initial validation of the Chronic Cancer Experiences
Questionnaire (CCEQ).
AB - BACKGROUND: Many advanced cancers are managed as chronic diseases, yet there are
currently no international guidelines for the support of patients living with
chronic cancer. It is important to understand whether care and service
arrangements meet the needs of this rapidly growing patient group. This study
aimed to develop and validate a questionnaire to capture patients' experiences of
living with chronic cancer and their views of clinical and support services.
METHODS: The research was carried out between 1 July 2010 and 21 February 2013. A
conceptual framework and initial item bank were derived from prior interviews
with 56 patients with chronic cancer. Items were reviewed by 4 oncologists and 1
clinical nurse specialist and during 2 focus groups with 9 patients. Pilot
questionnaires were completed by 416 patients across 5 cancer units. Item
selection and scale reliability was explored using descriptive data, exploratory
factor analysis, internal consistency analyses, multitrait scaling analyses and
known-groups comparisons. RESULTS: The final Chronic Cancer Experiences
Questionnaire (CCEQ) includes 75 items. 62 items contribute to 14 subscales with
internal consistency between alpha 0.68-0.88 and minimal scaling errors. Known
groups comparisons confirmed subscale utility in distinguishing between patient
groups. Subscales were labelled: managing appointments, coordination of care,
general practitioner involvement, clinical trials, information and questions,
making treatment decisions, symptom non-reporting, key worker, limitations,
sustaining normality, financial advice, worries and anxieties, sharing feelings
with others, and accessing support. 13 items assessing symptom experiences were
retained as single items. CONCLUSIONS: The CCEQ has the potential to be used as a
clinical instrument to assess patient experiences of chronic cancer or to screen
for patient needs. It may also be used as an outcome measure for evaluating
programmes and models of care and may identify areas for service development that
could ultimately improve the care and support received by patients with chronic
cancer.
PMID- 27511002
TI - Specialized Networks for Social Cognition: A Defining Role for the Oxytocin
Receptor.
PMID- 27511003
TI - Distributed Representation of "What" and "Where" Information in the
Parahippocampal Region.
PMID- 27511004
TI - GABAB Receptors Tune Cortical Feedback to the Olfactory Bulb.
AB - Sensory perception emerges from the confluence of sensory inputs that encode the
composition of external environment and top-down feedback that conveys
information from higher brain centers. In olfaction, sensory input activity is
initially processed in the olfactory bulb (OB), serving as the first central
relay before being transferred to the olfactory cortex. In addition, the OB
receives dense connectivity from feedback projections, so the OB has the capacity
to implement a wide array of sensory neuronal computation. However, little is
known about the impact and the regulation of this cortical feedback. Here, we
describe a novel mechanism to gate glutamatergic feedback selectively from the
anterior olfactory cortex (AOC) to the OB. Combining in vitro and in vivo
electrophysiological recordings, optogenetics, and fiber-photometry-based calcium
imaging applied to wild-type and conditional transgenic mice, we explore the
functional consequences of circuit-specific GABA type-B receptor (GABABR)
manipulation. We found that activation of presynaptic GABABRs specifically
depresses synaptic transmission from the AOC to OB inhibitory interneurons, but
spares direct excitation to principal neurons. As a consequence, feedforward
inhibition of spontaneous and odor-evoked activity of principal neurons is
diminished. We also show that tunable cortico-bulbar feedback is critical for
generating beta, but not gamma, OB oscillations. Together, these results show
that GABABRs on cortico-bulbar afferents gate excitatory transmission in a target
specific manner and thus shape how the OB integrates sensory inputs and top-down
information. SIGNIFICANCE STATEMENT: The olfactory bulb (OB) receives top-down
inputs from the olfactory cortex that produce direct excitation and feedforward
inhibition onto mitral and tufted cells, the principal neurons. The functional
role of this feedback and the mechanisms regulating the balance of feedback
excitation and inhibition remain unknown. We found that GABAB receptors are
expressed in cortico-bulbar axons that synapse on granule cells and receptor
activation reduces the feedforward inhibition of spontaneous and odor-driven
mitral and tufted cells' firing activity. In contrast, direct excitatory inputs
to these principal neurons remain unchanged. This study demonstrates that
activation of GABAB receptors biases the excitation/inhibition balance provided
by cortical inputs to the OB, leading to profound effects on early stages of
sensory information processing.
PMID- 27511005
TI - Silent Expectations: Dynamic Causal Modeling of Cortical Prediction and Attention
to Sounds That Weren't.
AB - There is increasing evidence that human perception is realized by a hierarchy of
neural processes in which predictions sent backward from higher levels result in
prediction errors that are fed forward from lower levels, to update the current
model of the environment. Moreover, the precision of prediction errors is thought
to be modulated by attention. Much of this evidence comes from paradigms in which
a stimulus differs from that predicted by the recent history of other stimuli
(generating a so-called "mismatch response"). There is less evidence from
situations where a prediction is not fulfilled by any sensory input (an
"omission" response). This situation arguably provides a more direct measure of
"top-down" predictions in the absence of confounding "bottom-up" input. We
applied Dynamic Causal Modeling of evoked electromagnetic responses recorded by
EEG and MEG to an auditory paradigm in which we factorially crossed the presence
versus absence of "bottom-up" stimuli with the presence versus absence of "top
down" attention. Model comparison revealed that both mismatch and omission
responses were mediated by increased forward and backward connections, differing
primarily in the driving input. In both responses, modeling results suggested
that the presence of attention selectively modulated backward "prediction"
connections. Our results provide new model-driven evidence of the pure top-down
prediction signal posited in theories of hierarchical perception, and highlight
the role of attentional precision in strengthening this prediction. SIGNIFICANCE
STATEMENT: Human auditory perception is thought to be realized by a network of
neurons that maintain a model of and predict future stimuli. Much of the evidence
for this comes from experiments where a stimulus unexpectedly differs from
previous ones, which generates a well-known "mismatch response." But what happens
when a stimulus is unexpectedly omitted altogether? By measuring the brain's
electromagnetic activity, we show that it also generates an "omission response"
that is contingent on the presence of attention. We model these responses
computationally, revealing that mismatch and omission responses only differ in
the location of inputs into the same underlying neuronal network. In both cases,
we show that attention selectively strengthens the brain's prediction of the
future.
PMID- 27511006
TI - Compartment-Dependent Degradation of Mutant Huntingtin Accounts for Its
Preferential Accumulation in Neuronal Processes.
AB - In neurodegenerative diseases caused by misfolded proteins, including
Huntington's disease (HD), the neuronal processes and terminals are particularly
prone to the accumulation of misfolded proteins, leading to axonal and synaptic
dysfunction. This compartment-dependent accumulation can result from either the
altered transport of misfolded proteins or impaired protein degradation. Mutant
huntingtin (mHtt), the HD protein, is known to affect intracellular transport and
can be degraded by the proteasome and autophagy, but how mHtt accumulates in the
neuronal processes, an early pathological event in the brains of HD patients,
still remains unclear. Using an "optical pulse-chase" assay that can quantify
protein degradation in specific subcellular regions, we found that neuronal mHtt
is removed faster in the cell body than in neurites. Furthermore, mHtt is cleared
more rapidly in astrocytes than in neurons. The ubiquitin-proteasome system plays
a much bigger role than autophagy in degrading soluble mHtt via K48
ubiquitination in both the cytoplasm and processes of neurons and astrocytes. By
injecting adenoviral vectors expressing mHtt into the mouse brain, we confirmed
that mHtt is removed more slowly in neurites than in the cytoplasm of the cell
body of neurons. Our findings provide evidence for the cell type- and compartment
dependent degradation of mHtt and explain why mHtt preferentially accumulates and
aggregates in the neuropils of vulnerable neurons. In addition, our findings
suggest that enhancing proteasomal activity could be an effective way to reduce
the preferential accumulation of soluble mHtt in neuronal processes. SIGNIFICANCE
STATEMENT: The clearance of misfolded proteins is key to preventing
neurodegeneration in Huntington's disease, but how mutant huntingtin (mHtt)
accumulates differentially in different cell types and subcellular regions
remains unclear. We found mHtt is cleared slowly in neuronal processes compared
with the cytoplasm and is cleared more efficiently in astrocytes than in neurons.
Moreover, this compartment-dependent degradation of soluble mHtt is mediated
primarily by the ubiquitin-proteasome system rather than autophagy. Our findings
imply that enhancing proteasome activity could be an efficient way to clear
soluble misfolded proteins in the neuronal processes.
PMID- 27511007
TI - Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay
Reach-to-Grasp Task.
AB - The computational role of spike time synchronization at millisecond precision
among neurons in the cerebral cortex is hotly debated. Studies performed on data
of limited size provided experimental evidence that low-order correlations occur
in relation to behavior. Advances in electrophysiological technology to record
from hundreds of neurons simultaneously provide the opportunity to observe
coordinated spiking activity of larger populations of cells. We recently
published a method that combines data mining and statistical evaluation to search
for significant patterns of synchronous spikes in massively parallel spike trains
(Torre et al., 2013). The method solves the computational and multiple testing
problems raised by the high dimensionality of the data. In the current study, we
used our method on simultaneous recordings from two macaque monkeys engaged in an
instructed-delay reach-to-grasp task to determine the emergence of spike
synchronization in relation to behavior. We found a multitude of synchronous
spike patterns aligned in both monkeys along a preferential mediolateral
orientation in brain space. The occurrence of the patterns is highly specific to
behavior, indicating that different behaviors are associated with the
synchronization of different groups of neurons ("cell assemblies"). However,
pooled patterns that overlap in neuronal composition exhibit no specificity,
suggesting that exclusive cell assemblies become active during different
behaviors, but can recruit partly identical neurons. These findings are
consistent across multiple recording sessions analyzed across the two monkeys.
SIGNIFICANCE STATEMENT: Neurons in the brain communicate via electrical impulses
called spikes. How spikes are coordinated to process information is still largely
unknown. Synchronous spikes are effective in triggering a spike emission in
receiving neurons and have been shown to occur in relation to behavior in a
number of studies on simultaneous recordings of few neurons. We recently
published a method to extend this type of investigation to larger data. Here, we
apply it to simultaneous recordings of hundreds of neurons from the motor cortex
of macaque monkeys performing a motor task. Our analysis reveals groups of
neurons selectively synchronizing their activity in relation to behavior, which
sheds new light on the role of synchrony in information processing in the
cerebral cortex.
PMID- 27511008
TI - Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic
Rehabilitation: Elements of Success, Failure, and Dependence.
AB - Robot therapy promotes functional recovery after spinal cord injury (SCI) in
animal and clinical studies. Trunk actions are important in adult rats spinalized
as neonates (NTX rats) that walk autonomously. Quadrupedal robot rehabilitation
was tested using an implanted orthosis at the pelvis. Trunk cortical
reorganization follows such rehabilitation. Here, we test the functional outcomes
of such training. Robot impedance control at the pelvis allowed hindlimb, trunk,
and forelimb mechanical interactions. Rats gradually increased weight support.
Rats showed significant improvement in hindlimb stepping ability, quadrupedal
weight support, and all measures examined. Function in NTX rats both before and
after training showed bimodal distributions, with "poor" and "high weight
support" groupings. A total of 35% of rats initially classified as "poor" were
able to increase their weight-supported step measures to a level considered "high
weight support" after robot training, thus moving between weight support groups.
Recovered function in these rats persisted on treadmill with the robot both
actuated and nonactuated, but returned to pretraining levels if they were
completely disconnected from the robot. Locomotor recovery in robot
rehabilitation of NTX rats thus likely included context dependence and/or
incorporation of models of robot mechanics that became essential parts of their
learned strategy. Such learned dependence is likely a hurdle to autonomy to be
overcome for many robot locomotor therapies. Notwithstanding these limitations,
trunk-based quadrupedal robot rehabilitation helped the rats to visit mechanical
states they would never have achieved alone, to learn novel coordinations, and to
achieve major improvements in locomotor function. SIGNIFICANCE STATEMENT:
Neonatal spinal transected rats without any weight support can be taught weight
support as adults by using robot rehabilitation at trunk. No adult control rats
with neonatal spinal transections spontaneously achieve similar changes. The
robot rehabilitation system can be inactivated and the skills that were learned
persist. Responding rats cannot be detached from the robot altogether, a
dependence develops in the skill learned. From data and analysis here, the
likelihood of such rats to respond to the robot therapy can also now be
predicted. These results are all novel. Understanding trunk roles in voluntary
and spinal reflex integration after spinal cord injury and in recovery of
function are broadly significant for basic and clinical understanding of motor
function.
PMID- 27511009
TI - Amyloid Precursor Protein Protects Neuronal Network Function after Hypoxia via
Control of Voltage-Gated Calcium Channels.
AB - Acute cerebral ischemia and chronic neurovascular diseases share various common
mechanisms with neurodegenerative diseases, such as disturbed cellular calcium
and energy homeostasis and accumulation of toxic metabolites. A link between
these conditions may be constituted by amyloid precursor protein (APP), which
plays a pivotal role in the pathogenesis of Alzheimer's disease, but has also
been associated with the response to acute hypoxia and regulation of calcium
homeostasis. We therefore studied hypoxia-induced loss of function and recovery
upon reoxygenation in hippocampal slices of mice lacking APP (APP(-/-)) or
selectively expressing its soluble extracellular domain (APPsalpha-KI). Transient
hypoxia disrupted electrical activity at the network and cellular level. In mice
lacking APP, these impairments were significantly more severe, showing increased
rise of intracellular calcium, faster loss of function, and higher incidence of
spreading depression. Likewise, functional recovery upon reoxygenation was much
slower and less complete than in controls. Most of these deficits were rescued by
selective expression of the soluble extracellular fragment APPsalpha, or by
pharmacological block of L-type calcium channels. We conclude that APP supports
neuronal resistance toward acute hypoxia. This effect is mediated by the secreted
APPsalpha-domain and involves L-type calcium channels. SIGNIFICANCE STATEMENT:
Amyloid precursor protein (APP) is involved in the pathophysiology of Alzheimer's
disease, but its normal function in the brain remains elusive. Here, we describe
a neuroprotective role of the protein in acute hypoxia. Functional recovery of
mouse hippocampal networks after transient reduction of oxygen supply was
strongly impaired in animals lacking APP. Most protective effects are mediated by
the soluble extracellular fragment APPsalpha and involve L-type calcium channels.
Thus, APP contributes to calcium homeostasis in situations of metabolic stress.
This finding may shed light on the physiological function of APP and may be
important for understanding mechanisms of neurodegenerative diseases.
PMID- 27511010
TI - Ventral Midline Thalamus Is Critical for Hippocampal-Prefrontal Synchrony and
Spatial Working Memory.
AB - Maintaining behaviorally relevant information in spatial working memory (SWM)
requires functional synchrony between the dorsal hippocampus and medial
prefrontal cortex (mPFC). However, the mechanism that regulates synchrony between
these structures remains unknown. Here, we used a unique dual-task approach to
compare hippocampal-prefrontal synchrony while rats switched between an SWM
dependent task and an SWM-independent task within a single behavioral session. We
show that task-specific representations in mPFC neuronal populations are
accompanied by SWM-specific oscillatory synchrony and directionality between the
dorsal hippocampus and mPFC. We then demonstrate that transient inactivation of
the reuniens and rhomboid (Re/Rh) nuclei of the ventral midline thalamus
abolished only the SWM-specific activity patterns that were seen during dual-task
sessions within the hippocampal-prefrontal circuit. These findings demonstrate
that Re/Rh facilitate bidirectional communication between the dorsal hippocampus
and mPFC during SWM, providing evidence for a causal role of Re/Rh in regulating
hippocampal-prefrontal synchrony and SWM-directed behavior. SIGNIFICANCE
STATEMENT: Hippocampal-prefrontal synchrony has long been thought to be critical
for spatial working memory (SWM) and the ventral midline thalamic reuniens and
rhomboid nuclei (Re/Rh) have long been considered a potential site for
synchronizing the hippocampus and medial prefrontal cortex. However, the
hypothesis that Re/Rh are critical for hippocampal-prefrontal synchrony and SWM
has not been tested. We first used a dual-task approach to identify SWM-specific
patterns of hippocampal-prefrontal synchrony. We then demonstrated that Re/Rh
inactivation concurrently disrupted SWM-specific behavior and the SWM-specific
patterns of hippocampal-prefrontal synchrony seen during dual-task performance.
These results provide the first direct evidence that Re/Rh contribute to SWM by
modulating hippocampal-prefrontal synchrony.
PMID- 27511011
TI - BDNF Val66Met Polymorphism Interacts with Sleep Consolidation to Predict Ability
to Create New Declarative Memories.
AB - It is hypothesized that a fundamental function of sleep is to restore an
individual's day-to-day ability to learn and to constantly adapt to a changing
environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is
among the key regulators that shape brain plasticity. However, advancing age and
carrying the BDNF Met allele were both identified as factors that potentially
reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the
moderating role of BDNF polymorphism on sleep and next-morning learning ability
in 107 nondemented individuals who were between 55 and 84 years of age. All
subjects were tested with 1 night of in-laboratory polysomnography followed by a
cognitive evaluation the next morning. We found that in subjects carrying the
BDNF Val66Val polymorphism, consolidated sleep was associated with significantly
better performance on hippocampus-dependent episodic memory tasks the next
morning (beta-values from 0.290 to 0.434, p <= 0.01). In subjects carrying at
least one copy of the BDNF Met allele, a more consolidated sleep was not
associated with better memory performance in most memory tests (beta-values from
0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep
consolidation was associated with poorer performance in learning a short story
presented verbally in Met allele carriers (beta = -0.585, p = 0.005). This study
provides new evidence regarding the interacting roles of consolidated sleep and
BDNF polymorphism in the ability to learn and stresses the importance of
considering BDNF polymorphism when studying how sleep affects cognition.
SIGNIFICANCE STATEMENT: Individuals with the BDNF Val/Val (valine allele)
polymorphism showed better memory performance after a night of consolidated
sleep. However, we observed that middle-aged and older individuals who are
carriers of the BDNF Met allele displayed no positive association between sleep
quality and their ability to learn the next morning. This interaction between
sleep and BDNF polymorphism was more salient for hippocampus-dependent tasks than
for other cognitive tasks. Our results support the hypothesis that reduced
activity-dependent secretion of BDNF impairs the benefits of sleep on synaptic
plasticity and next-day memory. Our work advances the field by revealing new
evidence of a clear genetic heterogeneity in how sleep consolidation contributes
to the ability to learn.
PMID- 27511012
TI - 3D Visual Response Properties of MSTd Emerge from an Efficient, Sparse Population
Code.
AB - Neurons in the dorsal subregion of the medial superior temporal (MSTd) area of
the macaque respond to large, complex patterns of retinal flow, implying a role
in the analysis of self-motion. Some neurons are selective for the expanding
radial motion that occurs as an observer moves through the environment
("heading"), and computational models can account for this finding. However,
ample evidence suggests that MSTd neurons exhibit a continuum of visual response
selectivity to large-field motion stimuli. Furthermore, the underlying
computational principles by which these response properties are derived remain
poorly understood. Here we describe a computational model of macaque MSTd based
on the hypothesis that neurons in MSTd efficiently encode the continuum of large
field retinal flow patterns on the basis of inputs received from neurons in MT
with receptive fields that resemble basis vectors recovered with non-negative
matrix factorization. These assumptions are sufficient to quantitatively simulate
neurophysiological response properties of MSTd cells, such as 3D translation and
rotation selectivity, suggesting that these properties might simply be a
byproduct of MSTd neurons performing dimensionality reduction on their inputs. At
the population level, model MSTd accurately predicts eye velocity and heading
using a sparse distributed code, consistent with the idea that biological MSTd
might be well equipped to efficiently encode various self-motion variables. The
present work aims to add some structure to the often contradictory findings about
macaque MSTd, and offers a biologically plausible account of a wide range of
visual response properties ranging from single-unit selectivity to population
statistics. SIGNIFICANCE STATEMENT: Using a dimensionality reduction technique
known as non-negative matrix factorization, we found that a variety of medial
superior temporal (MSTd) neural response properties could be derived from MT-like
input features. The responses that emerge from this technique, such as 3D
translation and rotation selectivity, spiral tuning, and heading selectivity, can
account for a number of empirical results. These findings (1) provide a further
step toward a scientific understanding of the often nonintuitive response
properties of MSTd neurons; (2) suggest that response properties, such as complex
motion tuning and heading selectivity, might simply be a byproduct of MSTd
neurons performing dimensionality reduction on their inputs; and (3) imply that
motion perception in the cortex is consistent with ideas from the efficient
coding and free-energy principles.
PMID- 27511013
TI - Medial Orbitofrontal Neurons Preferentially Signal Cues Predicting Changes in
Reward during Unblocking.
AB - The orbitofrontal cortex (OFC) has been broadly implicated in the ability to use
the current value of expected outcomes to guide behavior. Although value
correlates have been prominently reported in lateral OFC, they are more often
associated with more medial areas. Further, recent studies in primates have
suggested a dissociation in which the lateral OFC is involved in credit
assignment and representation of reward identity and more medial areas are
critical to representing value. Previously, we used unblocking to test more
specifically what information about outcomes is represented by OFC neurons in
rats; consistent with the proposed dichotomy between the lateral and medial OFC,
we found relatively little linear value coding in the lateral OFC (Lopatina et
al., 2015). Here we have repeated this experiment, recording in the medial OFC,
to test whether such value signals might be found there. Neurons were recorded in
an unblocking task as rats learned about cues that signaled either more, less, or
the same amount of reward. We found that medial OFC neurons acquired responses to
these cues; however, these responses did not signal different reward values
across cues. Surprisingly, we found that cells developed responses to cues
predicting a change, particularly a decrease, in reward value. This is consistent
with a special role for medial OFC in representing current value to support
devaluation/revaluation sensitive changes in behavior. SIGNIFICANCE STATEMENT:
This study uniquely examines encoding in rodent mOFC at the single-unit level in
response to cues that predict more, less, or no change in reward in rats during
training in a Pavlovian unblocking task, finding more cells responding to change
predictive cues and stronger activity in response to cues predictive of less
reward.
PMID- 27511014
TI - The Face-Processing Network Is Resilient to Focal Resection of Human Visual
Cortex.
AB - Human face perception requires a network of brain regions distributed throughout
the occipital and temporal lobes with a right hemisphere advantage. Present
theories consider this network as either a processing hierarchy beginning with
the inferior occipital gyrus (occipital face area; IOG-faces/OFA) or a multiple
route network with nonhierarchical components. The former predicts that removing
IOG-faces/OFA will detrimentally affect downstream stages, whereas the latter
does not. We tested this prediction in a human patient (Patient S.P.) requiring
removal of the right inferior occipital cortex, including IOG-faces/OFA. We
acquired multiple fMRI measurements in Patient S.P. before and after a preplanned
surgery and multiple measurements in typical controls, enabling both within
subject/across-session comparisons (Patient S.P. before resection vs Patient S.P.
after resection) and between-subject/across-session comparisons (Patient S.P. vs
controls). We found that the spatial topology and selectivity of downstream
ipsilateral face-selective regions were stable 1 and 8 month(s) after surgery.
Additionally, the reliability of distributed patterns of face selectivity in
Patient S.P. before versus after resection was not different from across-session
reliability in controls. Nevertheless, postoperatively, representations of visual
space were typical in dorsal face-selective regions but atypical in ventral face
selective regions and V1 of the resected hemisphere. Diffusion weighted imaging
in Patient S.P. and controls identifies white matter tracts connecting
retinotopic areas to downstream face-selective regions, which may contribute to
the stable and plastic features of the face network in Patient S.P. after
surgery. Together, our results support a multiple-route network of face
processing with nonhierarchical components and shed light on stable and plastic
features of high-level visual cortex following focal brain damage. SIGNIFICANCE
STATEMENT: Brain networks consist of interconnected functional regions commonly
organized in processing hierarchies. Prevailing theories predict that damage to
the input of the hierarchy will detrimentally affect later stages. We tested this
prediction with multiple brain measurements in a rare human patient requiring
surgical removal of the putative input to a network processing faces.
Surprisingly, the spatial topology and selectivity of downstream face-selective
regions are stable after surgery. Nevertheless, representations of visual space
were typical in dorsal face-selective regions but atypical in ventral face
selective regions and V1. White matter connections from outside the face network
may support these stable and plastic features. As processing hierarchies are
ubiquitous in biological and nonbiological systems, our results have pervasive
implications for understanding the construction of resilient networks.
PMID- 27511015
TI - SIRT1 Mediates Depression-Like Behaviors in the Nucleus Accumbens.
AB - Depression is a recurring and life-threatening illness that affects up to 120
million people worldwide. In the present study, we show that chronic social
defeat stress, an ethologically validated model of depression in mice, increases
SIRT1 levels in the nucleus accumbens (NAc), a key brain reward region. Increases
in SIRT1, a well characterized class III histone deacetylase, after chronic
social defeat suggest a role for this enzyme in mediating depression-like
behaviors. When resveratrol, a pharmacological activator of SIRT1, was directly
infused bilaterally into the NAc, we observed an increase in depression- and
anxiety-like behaviors. Conversely, intra-NAc infusions of EX-527, a SIRT1
antagonist, reduced these behaviors; EX-527 also reduced acute stress responses
in stress-naive mice. Next, we increased SIRT1 levels directly in NAc by use of
viral-mediated gene transfer and observed an increase in depressive- and anxiety
like behaviors when mice were assessed in the open-field, elevated-plus-maze, and
forced swim tests. Using a Cre-inducible viral vector system to overexpress SIRT1
selectively in dopamine D1 or D2 subpopulations of medium spiny neurons (MSNs) in
the NAc, we found that SIRT1 promotes depressive-like behaviors only when
overexpressed in D1 MSNs, with no effect seen in D2 MSNs. Conversely, selective
ablation of SIRT1 in the NAc using viral-Cre in floxed Sirt1 mice resulted in
decreased depression- and anxiety-like behaviors. Together, these results
demonstrate that SIRT1 plays an essential role in the NAc in regulating mood
related behavioral abnormalities and identifies a novel signaling pathway for the
development of innovative antidepressants to treat major depressive disorders.
SIGNIFICANCE STATEMENT: In this study, we demonstrate a pivotal role for SIRT1 in
anxiety- and depression-like behaviors in the nucleus accumbens (NAc), a key
brain reward region. We show that stress stably induces SIRT1 expression in this
brain region and that altering SIRT1 activity using a pharmacological or genetic
approach regulates anxiety- and depression-like behaviors. These results suggest
that SIRT1 plays an essential role in regulating mood-related behaviors and
introduces a novel signaling pathway for the development of innovative
antidepressants to treat depression and other stress-related disorders. A recent
groundbreaking publication by the CONVERGE Consortium (2015) identified a
reproducible association of the SIRT1 locus with major depression in humans.
Therefore, our results are timely and have significant translational relevance.
PMID- 27511016
TI - Transient Modulations of Neural Responses to Heartbeats Covary with Bodily Self
Consciousness.
AB - Recent research has investigated self-consciousness associated with the
multisensory processing of bodily signals (e.g., somatosensory, visual,
vestibular signals), a notion referred to as bodily self-consciousness, and these
studies have shown that the manipulation of bodily inputs induces changes in
bodily self-consciousness such as self-identification. Another line of research
has highlighted the importance of signals from the inside of the body (e.g.,
visceral signals) and proposed that neural representations of internal bodily
signals underlie self-consciousness, which to date has been based on
philosophical inquiry, clinical case studies, and behavioral studies. Here, we
investigated the relationship of bodily self-consciousness with the neural
processing of internal bodily signals. By combining electrical neuroimaging,
analysis of peripheral physiological signals, and virtual reality technology in
humans, we show that transient modulations of neural responses to heartbeats in
the posterior cingulate cortex covary with changes in bodily self-consciousness
induced by the full-body illusion. Additional analyses excluded that measured
basic cardiorespiratory parameters or interoceptive sensitivity traits could
account for this finding. These neurophysiological data link experimentally the
cortical mapping of the internal body to self-consciousness. SIGNIFICANCE
STATEMENT: What are the brain mechanisms of self-consciousness? Prominent views
propose that the neural processing associated with signals from the internal
organs (such as the heart and the lung) plays a critical role in self
consciousness. Although this hypothesis dates back to influential views in
philosophy and psychology (e.g., William James), definitive experimental evidence
supporting this idea is lacking despite its recent impact in neuroscience. In the
present study, we show that posterior cingulate activities responding to
heartbeat signals covary with changes in participants' conscious self
identification with a body that were manipulated experimentally using virtual
reality technology. Our finding provides important neural evidence about the long
standing proposal that self-consciousness is linked to the cortical processing of
internal bodily signals.
PMID- 27511017
TI - Acute Stress Suppresses Synaptic Inhibition and Increases Anxiety via
Endocannabinoid Release in the Basolateral Amygdala.
AB - Stress and glucocorticoids stimulate the rapid mobilization of endocannabinoids
in the basolateral amygdala (BLA). Cannabinoid receptors in the BLA contribute to
anxiogenesis and fear-memory formation. We tested for rapid glucocorticoid
induced endocannabinoid regulation of synaptic inhibition in the rat BLA.
Glucocorticoid application to amygdala slices elicited a rapid, nonreversible
suppression of spontaneous, but not evoked, GABAergic synaptic currents in BLA
principal neurons; the effect was also seen with a membrane-impermeant
glucocorticoid, but not with intracellular glucocorticoid application,
implicating a membrane-associated glucocorticoid receptor. The glucocorticoid
suppression of GABA currents was not blocked by antagonists of nuclear
corticosteroid receptors, or by inhibitors of gene transcription or protein
synthesis, but was blocked by inhibiting postsynaptic G-protein activity,
suggesting a postsynaptic nongenomic steroid signaling mechanism that stimulates
the release of a retrograde messenger. The rapid glucocorticoid-induced
suppression of inhibition was prevented by blocking CB1 receptors and 2
arachidonoylglycerol (2-AG) synthesis, and it was mimicked and occluded by CB1
receptor agonists, indicating it was mediated by the retrograde release of the
endocannabinoid 2-AG. The rapid glucocorticoid effect in BLA neurons in vitro was
occluded by prior in vivo acute stress-induced, or prior in vitro glucocorticoid
induced, release of endocannabinoid. Acute stress also caused an increase in
anxiety-like behavior that was attenuated by blocking CB1 receptor activation and
inhibiting 2-AG synthesis in the BLA. Together, these findings suggest that acute
stress causes a long-lasting suppression of synaptic inhibition in BLA neurons
via a membrane glucocorticoid receptor-induced release of 2-AG at GABA synapses,
which contributes to stress-induced anxiogenesis. SIGNIFICANCE STATEMENT: We
provide a cellular mechanism in the basolateral amygdala (BLA) for the rapid
stress regulation of anxiogenesis in rats. We demonstrate a nongenomic
glucocorticoid induction of long-lasting suppression of synaptic inhibition that
is mediated by retrograde endocannabinoid release at GABA synapses. The rapid
glucocorticoid-induced endocannabinoid suppression of synaptic inhibition is
initiated by a membrane-associated glucocorticoid receptor in BLA principal
neurons. We show that acute stress increases anxiety-like behavior via an
endocannabinoid-dependent mechanism centered in the BLA. The stress-induced
endocannabinoid modulation of synaptic transmission in the BLA contributes,
therefore, to the stress regulation of anxiety, and may play a role in anxiety
disorders of the amygdala.
PMID- 27511018
TI - APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer's Disease.
AB - Prior work suggests that amyloid precursor protein (APP) can function as a
proinflammatory receptor on immune cells, such as monocytes and microglia.
Therefore, we hypothesized that APP serves this function in microglia during
Alzheimer's disease. Although fibrillar amyloid beta (Abeta)-stimulated cytokine
secretion from both wild-type and APP knock-out (mAPP(-/-)) microglial cultures,
oligomeric Abeta was unable to stimulate increased secretion from mAPP(-/-)
cells. This was consistent with an ability of oligomeric Abeta to bind APP.
Similarly, intracerebroventricular infusions of oligomeric Abeta produced less
microgliosis in mAPP(-/-) mice compared with wild-type mice. The mAPP(-/-) mice
crossed to an APP/PS1 transgenic mouse line demonstrated reduced microgliosis and
cytokine levels and improved memory compared with wild-type mice despite robust
fibrillar Abeta plaque deposition. These data define a novel function for
microglial APP in regulating their ability to acquire a proinflammatory phenotype
during disease. SIGNIFICANCE STATEMENT: A hallmark of Alzheimer's disease (AD)
brains is the accumulation of amyloid beta (Abeta) peptide within plaques
robustly invested with reactive microglia. This supports the notion that Abeta
stimulation of microglial activation is one source of brain inflammatory changes
during disease. Abeta is a cleavage product of the ubiquitously expressed amyloid
precursor protein (APP) and is able to self-associate into a wide variety of
differently sized and structurally distinct multimers. In this study, we
demonstrate both in vitro and in vivo that nonfibrillar, oligomeric forms of
Abeta are able to interact with the parent APP protein to stimulate microglial
activation. This provides a mechanism by which metabolism of APP results in
possible autocrine or paracrine Abeta production to drive the microgliosis
associated with AD brains.
PMID- 27511019
TI - Cell-Specific Cholinergic Modulation of Excitability of Layer 5B Principal
Neurons in Mouse Auditory Cortex.
AB - The neuromodulator acetylcholine (ACh) is crucial for several cognitive
functions, such as perception, attention, and learning and memory. Whereas, in
most cases, the cellular circuits or the specific neurons via which ACh exerts
its cognitive effects remain unknown, it is known that auditory cortex (AC)
neurons projecting from layer 5B (L5B) to the inferior colliculus,
corticocollicular neurons, are required for cholinergic-mediated relearning of
sound localization after occlusion of one ear. Therefore, elucidation of the
effects of ACh on the excitability of corticocollicular neurons will bridge the
cell-specific and cognitive properties of ACh. Because AC L5B contains another
class of neurons that project to the contralateral cortex, corticocallosal
neurons, to identify the cell-specific mechanisms that enable corticocollicular
neurons to participate in sound localization relearning, we investigated the
effects of ACh release on both L5B corticocallosal and corticocollicular neurons.
Using in vitro electrophysiology and optogenetics in mouse brain slices, we found
that ACh generated nicotinic ACh receptor (nAChR)-mediated depolarizing
potentials and muscarinic ACh receptor (mAChR)-mediated hyperpolarizing
potentials in AC L5B corticocallosal neurons. In corticocollicular neurons, ACh
release also generated nAChR-mediated depolarizing potentials. However, in
contrast to the mAChR-mediated hyperpolarizing potentials in corticocallosal
neurons, ACh generated prolonged mAChR-mediated depolarizing potentials in
corticocollicular neurons. These prolonged depolarizing potentials generated
persistent firing in corticocollicular neurons, whereas corticocallosal neurons
lacking mAChR-mediated depolarizing potentials did not show persistent firing. We
propose that ACh-mediated persistent firing in corticocollicular neurons may
represent a critical mechanism required for learning-induced plasticity in AC.
SIGNIFICANCE STATEMENT: Acetylcholine (ACh) is crucial for cognitive functions.
Whereas in most cases the cellular circuits or the specific neurons via which ACh
exerts its cognitive effects remain unknown, it is known that auditory cortex
(AC) corticocollicular neurons projecting from layer 5B to the inferior
colliculus are required for cholinergic-mediated relearning of sound localization
after occlusion of one ear. Therefore, elucidation of the effects of ACh on the
excitability of corticocollicular neurons will bridge the cell-specific and
cognitive properties of ACh. Our results suggest that cell-specific ACh-mediated
persistent firing in corticocollicular neurons may represent a critical mechanism
required for learning-induced plasticity in AC. Moreover, our results provide
synaptic mechanisms via which ACh may mediate its effects on AC receptive fields.
PMID- 27511020
TI - Tonotopic Optimization for Temporal Processing in the Cochlear Nucleus.
AB - In the auditory system, sounds are processed in parallel frequency-tuned
circuits, beginning in the cochlea. Auditory nerve fibers reflect this tonotopy
and encode temporal properties of acoustic stimuli by "locking" discharges to a
particular stimulus phase. However, physiological constraints on phase-locking
depend on stimulus frequency. Interestingly, low characteristic frequency (LCF)
neurons in the cochlear nucleus improve phase-locking precision relative to their
auditory nerve inputs. This is proposed to arise through synaptic integration,
but the postsynaptic membrane's selectivity for varying levels of synaptic
convergence is poorly understood. The chick cochlear nucleus, nucleus
magnocellularis (NM), exhibits tonotopic distribution of both input and membrane
properties. LCF neurons receive many small inputs and have low input thresholds,
whereas high characteristic frequency (HCF) neurons receive few, large synapses
and require larger currents to spike. NM therefore presents an opportunity to
study how small membrane variations interact with a systematic topographic
gradient of synaptic inputs. We investigated membrane input selectivity and
observed that HCF neurons preferentially select faster input than their LCF
counterparts, and that this preference is tolerant of changes to membrane
voltage. We then used computational models to probe which properties are crucial
to phase-locking. The model predicted that the optimal arrangement of synaptic
and membrane properties for phase-locking is specific to stimulus frequency and
that the tonotopic distribution of input number and membrane excitability in NM
closely tracks a stimulus-defined optimum. These findings were then confirmed
physiologically with dynamic-clamp simulations of inputs to NM neurons.
SIGNIFICANCE STATEMENT: One way that neurons represent temporal information is by
phase-locking, which is discharging in response to a particular phase of the
stimulus waveform. In the auditory system, central neurons are optimized to
retain or improve phase-locking precision compared with input from the auditory
nerve. However, the difficulty of this computation varies systematically with
stimulus frequency. We examined properties that contribute to temporal processing
both physiologically and in a computational model. Neurons processing low
frequency input benefit from integration of many weak inputs, whereas those
processing higher frequencies progressively lose precision by integration of
multiple inputs. Here, we reveal general features of input-output optimization
that apply to all neurons that process time varying input.
PMID- 27511021
TI - miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers
to Spinal Cord Repair.
AB - Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic
mechanisms and extracellular barriers including inflammation. microRNA (miR)-155
5p is a small, noncoding RNA that negatively regulates mRNA translation. In
macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response
that could be toxic after SCI. miR-155 may also independently alter expression of
genes that regulate axon growth in neurons. Here, we hypothesized that miR-155
deletion would simultaneously improve axon growth and reduce neuroinflammation
after SCI by acting on both neurons and macrophages. New data show that miR-155
deletion attenuates inflammatory signaling in macrophages, reduces macrophage
mediated neuron toxicity, and increases macrophage-elicited axon growth by ~40%
relative to control conditions. In addition, miR-155 deletion increases
spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG)
neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion
augments conditioning lesion-induced intraneuronal expression of SPRR1A, a
regeneration-associated gene; ~50% more injured KO DRG neurons expressed SPRR1A
versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has
reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced
axon regeneration beyond the epicenter. Finally, in a model of spinal contusion
injury, miR-155 deletion improves locomotor function at postinjury times
corresponding with the arrival and maximal appearance of activated intraspinal
macrophages. In miR-155 KO mice, improved locomotor function is associated with
smaller contusion lesions and decreased accumulation of inflammatory macrophages.
Collectively, these data indicate that miR-155 is a novel therapeutic target
capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic
barriers to repair after SCI. SIGNIFICANCE STATEMENT: Axon regeneration after
spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and
extracellular barriers, including inflammation. Here, new data show that deleting
microRNA-155 (miR-155) affects both mechanisms and improves repair and functional
recovery after SCI. Macrophages lacking miR-155 have altered inflammatory
capacity, which enhances neuron survival and axon growth of cocultured neurons.
In addition, independent of macrophages, adult miR-155 KO neurons show enhanced
spontaneous axon growth. Using either spinal cord dorsal column crush or
contusion injury models, miR-155 deletion improves indices of repair and
recovery. Therefore, miR-155 has a dual role in regulating spinal cord repair and
may be a novel therapeutic target for SCI and other CNS pathologies.
PMID- 27511022
TI - The development of modified human Hsp70 (HSPA1A) and its production in the milk
of transgenic mice.
AB - The production of major human heat shock protein Hsp70 (HSPA1A) in a eukaryotic
expression system is needed for testing and possible medical applications. In
this study, transgenic mice were produced containing wild-type human Hsp70 allele
in the vector providing expression in the milk. The results indicated that human
Hsp70 was readily expressed in the transgenic animals but did not apparently
preserve its intact structure and, hence, it was not possible to purify the
protein using conventional isolation techniques. It was suggested that the
protein underwent glycosylation in the process of expression, and this quite
common modification for proteins expressed in the milk complicated its isolation.
To check this possibility, we mutated all presumptive sites of glycosylation and
tested the properties of the resulting modified Hsp70 expressed in E. coli. The
investigation demonstrated that the modified protein exhibited all beneficial
properties of the wild-type Hsp70 and was even superior to the latter for a few
parameters. Based on these results, a transgenic mouse strain was obtained which
expressed the modified Hsp70 in milk and which was easy to isolate using ATP
columns. Therefore, the developed construct can be explored in various
bioreactors for reliable manufacture of high quality, uniform, and reproducible
human Hsp70 for possible medical applications including neurodegenerative
diseases and cancer.
PMID- 27511023
TI - The expression of thioredoxin-1 in acute epinephrine stressed mice.
AB - Stress, a state of perceived threat to homeostasis, regulates a panel of
important physiological functions. The human mind and body respond to stress by
activating the sympathetic nervous system and secreting the catecholamines
epinephrine and norepinephrine in the "fight-or-flight" response. However, the
protective mechanism of acute stress is still unknown. In the present study, an
acute stress mouse model was constructed by intraperitoneal injection of
epinephrine (0.2 mg kg(-1)) for 4 h. Epinephrine treatment induced heat shock
70(Hsp70) expression in the stress responsive tissues, such as the cortex,
hippocampus, thymus, and kidney. Further, the expression of thioredoxin-1(Trx-1),
a cytoprotective protein, was also upregulated in these stress responsive
tissues. In addition, the phosphorylation of cAMP-response element binding
protein (CREB), a transcription factor of Trx-1, was increased after treatment
with epinephrine. The block of CREB activation by H89 inhibited the acute
epinephrine stress-induced Trx-1 and Hsp70 expression. Taken together, our data
suggest that acute stimuli of epinephrine induced Trx-1 expression through
activating CREB and may represent a protective role against stress.
PMID- 27511025
TI - Selective High-Resolution Detection of Membrane Protein-Ligand Interaction in
Native Membranes Using Trityl-Nitroxide PELDOR.
AB - The orchestrated interaction of transmembrane proteins with other molecules
mediates several crucial biological processes. Detergent solubilization may
significantly alter or even abolish such hetero-oligomeric interactions, which
makes observing them at high resolution in their native environment technically
challenging. Dipolar electron paramagnetic resonance (EPR) techniques such as
pulsed electro-electron double resonance (PELDOR) can provide very precise
distances within biomolecules. To concurrently determine the inter-subunit
interaction and the intra-subunit conformational changes in hetero-oligomeric
complexes, a combination of different spin labels is required. Orthogonal spin
labeling using a triarylmethyl (TAM) label in combination with a nitroxide label
is used to detect protein-ligand interactions in native lipid bilayers. This
approach provides a higher sensitivity and total selectivity and will greatly
facilitate the investigation of multimeric transmembrane complexes employing
different spin labels in the native lipid environment.
PMID- 27511024
TI - Hsp72 and Hsp90alpha mRNA transcription is characterised by large, sustained
changes in core temperature during heat acclimation.
AB - Increased intracellular heat shock protein-72 (Hsp72) and heat shock protein
90alpha (Hsp90alpha) have been implicated as important components of acquired
thermotolerance, providing cytoprotection during stress. This experiment
determined the physiological responses characterising increases in Hsp72 and
Hsp90alpha mRNA on the first and tenth day of 90-min heat acclimation (in 40.2
degrees C, 41.0 % relative humidity (RH)) or equivalent normothermic training (in
20 degrees C, 29 % RH). Pearson's product-moment correlation and stepwise
multiple regression were performed to determine relationships between
physiological [e.g. (Trec, sweat rate (SR) and heart rate (HR)] and training
variables (exercise duration, exercise intensity, work done), and the leukocyte
Hsp72 and Hsp90alpha mRNA responses via reverse transcription quantitative
polymerase chain reaction (RT-QPCR) (n = 15). Significant (p < 0.05) correlations
existed between increased Hsp72 and Hsp90alpha mRNA (r = 0.879). Increased core
temperature was the most important criteria for gene transcription with DeltaTrec
(r = 0.714), SR (r = 0.709), Trecfinal45 (r = 0.682), area under the curve where
Trec >= 38.5 degrees C (AUC38.5 degrees C; r = 0.678), peak Trec (r = 0.661),
duration Trec >= 38.5 degrees C (r = 0.650) and DeltaHR (r = 0.511) each
demonstrating a significant (p < 0.05) correlation with the increase in Hsp72
mRNA. The Trec AUC38.5 degrees C (r = 0.729), DeltaTrec (r = 0.691), peak Trec
(r = 0.680), Trecfinal45 (r = 0.678), SR (r = 0.660), duration Trec >= 38.5
degrees C (r = 0.629), the rate of change in Trec (r = 0.600) and DeltaHR (r =
0.531) were the strongest correlate with the increase in Hsp90alpha mRNA.
Multiple regression improved the model for Hsp90alpha mRNA only, when Trec
AUC38.5 degrees C and SR were combined. Training variables showed insignificant
(p > 0.05) weak (r < 0.300) relationships with Hsp72 and Hsp90alpha mRNA. Hsp72
and Hsp90alpha mRNA correlates were comparable on the first and tenth day. When
transcription of the related Hsp72 and Hsp90alpha mRNA is important, protocols
should rapidly induce large, prolonged changes in core temperature.
PMID- 27511026
TI - BES1 regulates the localization of the brassinosteroid receptor BRL3 within the
provascular tissue of the Arabidopsis primary root.
AB - Brassinosteroid (BR) hormones are important regulators of plant growth and
development. Recent studies revealed the cell-specific role of BRs in vascular
and stem cell development by the action of cell-specific BR receptor complexes
and downstream signaling components in Arabidopsis thaliana Despite the
importance of spatiotemporal regulation of hormone signaling in the control of
plant vascular development, the mechanisms that confer cellular specificity to BR
receptors within the vascular cells are not yet understood. The present work
shows that BRI1-like receptor genes 1 and 3 (BRL1 and BRL3) are differently
regulated by BRs. By using promoter deletion constructs of BRL1 and BRL3 fused to
GFP/GUS (green fluorescent protein/beta-glucuronidase) reporters in Arabidopsis,
analysis of their cell-specific expression and regulation by BRs in the root apex
has been carried out. We found that BRL3 expression is finely modulated by BRs in
different root cell types, whereas the location of BRL1 appears to be independent
of this hormone. Physiological and genetic analysis show a BR-dependent
expression of BRL3 in the root meristem. In particular, BRL3 expression requires
active BES1, a central transcriptional effector within the BRI1 pathway. ChIP
analysis showed that BES1 directly binds to the BRRE present in the BRL3 promoter
region, modulating its transcription in different subsets of cells of the root
apex. Overall our study reveals the existence of a cell-specific negative
feedback loop from BRI1-mediated BES1 transcription factor to BRL3 in phloem
cells, while contributing to a general understanding of the spatial control of
steroid signaling in plant development.
PMID- 27511027
TI - MRI signal intensity of anterior cruciate ligament graft after transtibial versus
anteromedial portal technique (TRANSIG): design of a randomized controlled
clinical trial.
AB - BACKGROUND: There are two primary surgical techniques to reconstruct the anterior
cruciate ligament (ACL), transtibial (TT) technique and anteromedial portal (AMP)
technique. Currently, there is no consensus which surgical technique elicits the
best clinical and functional outcomes. MRI-derived measures of the signal
intensity (SI) of the ACL graft have been described as an independent predictor
of graft properties. The purpose of this study is to compare the MRI derived SI
measurements of the ACL graft one year after ACL reconstruction, in order to
compare the outcomes of both the AMP and TT ACL reconstruction technique.
METHODS/DESIGN: Thirty-six patients will be included in a randomized controlled
trial. Patients who are admitted for primary unilateral ACL reconstruction will
be included in the study. Exclusion criteria are a history of previous surgery on
the ipsilateral knee, re-rupture of the ipsilateral ACL graft, associated
ligamentous injuries or meniscal tear of the ipsilateral knee, unhealthy
contralateral knee, contra-indications for MRI and a preference for one of the
two surgical techniques and/or orthopaedic surgeon. Primary outcome is MRI Signal
intensity ratio (SIR) of the ACL graft. Secondary outcome measures are the
International Knee Documentation Committee (IKDC) Knee Examination Form,the Knee
injury and Osteoarthritis Outcome Scores (KOOS) and the Anterior Cruciate
Ligament OsteoArthritis Score (ACLOAS). Differences between MRI SIR assessment
with the current MRI protocol (proton density weighted imaging protocol) and the
additional T2*-weighted gradient-echo protocol will be assessed. DISCUSSION:
There is no consensus regarding the TT or AMP ACL reconstruction technique. SI
measurements with MRI have been used in other clinical studies for evaluation of
the ACL graft and maturation after ACL reconstruction compared to clinical and
functional outcomes. This randomized controlled trial has been designed to
compare the TT technique with the AMP technique with the use of MRI SI of the
graft after ACL reconstruction. TRIAL REGISTRATION: Netherlands Trial Registry
NTR5410 (registered on August 24, 2015).
PMID- 27511029
TI - Australasian Musculoskeletal Imaging Group (AMSIG) annual scientific meeting
(ASM).
PMID- 27511028
TI - Emodin-Loaded PLGA-TPGS Nanoparticles Combined with Heparin Sodium-Loaded PLGA
TPGS Nanoparticles to Enhance Chemotherapeutic Efficacy Against Liver Cancer.
AB - PURPOSE: Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-alpha
tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs)
were prepared as a sustained and targeting delivery carrier and combined with
emodin (EMO)-loaded PLGA-TPGS nanoparticles (EPTNs), which were investigated
previously to form a combination therapy system for the treatment of liver
cancer. METHODS: To assess cellular uptake and evaluate the liver-targeting
capacity by analyzing the drug concentrations and frozen slices, HS/eosin-loaded
PLGA-TPGS nanoparticles, HS/fluorescein- loaded PLGA-TPGS nanoparticles and
EMO/C6-loaded PLGA-TPGS nanoparticles, which contained eosin, fluorescein and C6
as fluorescent probes, respectively, were also prepared. All of these
nanoparticles were characterized in terms of their size, size distribution,
surface charge, drug loading, encapsulation efficiency, in vitro release profile
and cellular uptake. The apoptosis of HepG2 cells induced by EPTNs in combination
with HPTNs was determined by Annexin V-FITC staining and PI labelling. RESULTS:
Transmission electron microscopy indicated that these nanoparticles were stably
dispersed spheres with sizes ranging from 100 to 200 nm. The results demonstrated
that fluorescent nanoparticles were internalized into HepG2 and HCa-F cells
efficiently and had improved liver-targeting properties. The combination of EPTNs
and HPTNs effectively inhibited cell growth in vitro and had a remarkable
synergistic anticancer effect in vivo. EPTNs combined with HPTNs induced HepG2
cell apoptosis with synergistic effects. The liver H&E slice images of a
hepatocarcinogenic mouse model indicated that EPTNs in combination with HPTNs
significantly suppressed tumour growth in vivo. CONCLUSIONS: The research
suggests that the combination therapy system of EPTNs and HPTNs could be a new
direction for liver cancer therapy.
PMID- 27511030
TI - MR imaging and ultrasonography findings of early myositis ossificans: a case
report.
AB - Myositis ossificans (MO) is a benign soft tissue lesion with non-neoplastic
heterotopic bone formation. MO in the intermediate and mature stages can be
easily diagnosed if characteristic imaging findings such as a peripheral zonal
pattern of ossification with variable thickness is observed. However, it is
difficult to correctly diagnose early MO because it can mimic malignancy
clinically, radiologically, and histopathologically. We report a case of early
pseudosarcomatous phase of non-traumatic MO with atypical imaging findings. A 59
year-old woman presented with pain followed by a mass in the left thigh within a
week. MR imaging and ultrasonography showed an intramuscular lesion with
preserved muscle fascicles in the vastus lateralis muscle. Intralesional
ossification or calcification was not seen on ultrasonography. A diagnosis of
myositis ossificans was made by ultrasonographically guided biopsy.
PMID- 27511031
TI - [Formulation of guidelines for microscopic endodontics suitable for the situation
of China].
AB - In order to promote the use of dental operating microscope in endodontics,
Society of Cariology and Endodontology of Chinese Stomatological Association
formulated these guidelines, after extensive consultation with related
authorities and careful reference to the available published materials and
literatures. It is hoped that these guidelines will be useful for dental
practitioners embarking on microscopic endodontics.
PMID- 27511032
TI - [An analysis of key points for root canal therapy technique].
AB - The success rate of root canal therapy(RCT)have been improved continuously along
with the advancement in RCT techniques in the past several decades. If standard
procedures of modern RCT techniques are strictly followed, the success rate of
RCT may exceed 90%. The success of RCT is mainly affected by such factors as
clear concept of the anatomy of root canals, proper mechanical and chemical
preparation and perfect filling of root canal system. If these factors are
sufficiently noted, a success is easy to achieve. Even though the primary RCT
fails, retreatment can further be conducted to save the diseased teeth.
PMID- 27511033
TI - [Analysis of the key points in the micro-endodontic treatment].
AB - Micro-endodontic treatment refers to the microscope-assisted endodontic treatment
techniques. The microscope offers a stereoscopic, enlarged image under great
magnification and illumination at a comfortable working position. It will greatly
promote the precision and improve the outcomes of endodontic treatment through
enhancing the ability to detect the complexity of the root canal system of teeth
that probably cannot be seen by the naked eyes, remove the infectious substances
in root canal more efficiently, provide a tight root canal obturation and carry
out effective retreatment procedures. The requirements of micro-endodontic
treatment are different from the conventional root canal therapy carried out
without microscope due to the complicated structure of the microscope. In order
to make the use of microscope easier, it is of great importance to learn how to
adjust the position of the operator and the patient, preset the angle of
objective lens and the eyepiece, select the proper magnification and instruments,
practice eye-hand cooperation under the microscope, etc. The purpose of this
article was to analyze the key points in the applications of the microscope in
endodontic treatment by reviewing the literature together with the author's
clinical experience.
PMID- 27511034
TI - [Theory and practice of minimally invasive endodontics].
AB - The primary goal of modern endodontic therapy is to achieve the long-term
retention of a functional tooth by preventing or treating pulpitis or apical
periodontitis is. The long-term retention of endodontically treated tooth is
correlated with the remaining amount of tooth tissue and the quality of the
restoration after root canal filling. In recent years, there has been rapid
progress and development in the basic research of endodontic biology, instrument
and applied materials, making treatment procedures safer, more accurate, and more
efficient. Thus, minimally invasive endodontics(MIE)has received increasing
attention at present. MIE aims to preserve the maximum of tooth structure during
root canal therapy, and the concept covers the whole process of diagnosis and
treatment of teeth. This review article focuses on describing the minimally
invasive concepts and operating essentials in endodontics, from diagnosis and
treatment planning to the access opening, pulp cavity finishing, root canal
cleaning and shaping, 3-dimensional root canal filling and restoration after root
canal treatment.
PMID- 27511035
TI - [Guidelines for the use of microscopes in endodontics].
PMID- 27511036
TI - [Diagnosis and treatment of a maxillary premolar with vertical root fracture: a
case report].
PMID- 27511037
TI - [The application of laser in endodontics].
AB - Since laser was introduced in the field of medicine in 1970's, its application
range has continuously expanded. The application of laser in endodontics also
increased due to its safety and effectiveness in dental treatments. The majority
of the laser application researches in dentistry focused on dentin
hypersensitivity, removal of carious tissues, tooth preparations, pulp capping or
pulpotomy, and root canal treatment. In this article, we reviewed literature on
the effects of laser in the treatments of dental and pulp diseases.
PMID- 27511038
TI - [Accuracy and reliability of three-dimensional craniofacial cone-beam CT
superimposition method based on voxel registration].
AB - OBJECTIVE: To set up a three-dimensional(3D)craniofacial cone-beam
CT(CBCT)superimposition method based on voxel registration, and evaluate the
accuracy and reliability of different reference superimposition areas. METHODS:
CBCT scans were taken on a dry skull for three times with a time-interval of two
weeks, and CBCT scans were taken on ten adult volunteers twice with a time
interval of one month. The 3D superimposition based on voxel registration was set
up by means of Analyze 12.0. The bilateral-zygomatic bone and anterior cranial
base were selected as different reference areas for voxel overlapping. The 3D
overlapping images were output into Geomagic Qualify 2013, and the surface
distances on different craniofacial regions were measured. Three operators
repeated three times of these superimposition and measurement. SPSS 19.0 were
used to analyze the accuracy and reliability. RESULTS: When bilateral-zygomatic
bone used as superimposition reference, the mean surface distance range of dry
skull were from 0.035 to 0.064 mm, and volunteers from 0.099 to 0.182 mm. When
the anterior cranial base used as superimposition reference, the mean surface
distance range of dry skull were from 0.038 to 0.071 mm, and volunteers from
0.127 to 0.218 mm. All these mean values were less than the CBCT voxel size 0.25
mm(P<0.05), and got sub-pixel precision. No significant difference was found
between the different operators at different times(P>0.05). CONCLUSIONS: This
study showed the high accuracy and reliability of 3D CBCT superimposition based
on voxel registration, either the anterior cranial base or the bilateral
zygomatic bone as reference. This method could be used for evaluating 3D
craniofacial treatment effects.
PMID- 27511039
TI - [Biomechanics analysis of the impact of maxillofacial injury on skull base
damage].
AB - OBJECTIVE: To analyze the impact of maxillofacial injury on skull base. METHODS:
A three-dimensional(3D)finite-element model of cranio-maxillofacial bone was
established by CT scan data. A lead cylinder in base diameter of 3 cm was
designed as an impactor. There regions(upper right maxilla, left infraorbital
margin and left zygomatic body)subjected to an impact at the speed of 8.6
m/s(about 30 km/h)was simulated. Thirteen landmarks at the skull base were
selected. The values of stress at the end of 0.5, 1.0, 1.5, 2.0 ms were obtained,
and the results were analyzed. RESULTS: The dynamic process of the fracture of
the jaw and the stress distribution and conduction of the skull base were
successfully simulated in three parts of the face. When the impact was on the
right maxillary bone region, the stress values of the three points(medial foramen
rotundum, medial foramen rotundum, anterior clivus reached the peak at each time
point, 26.2, 22.4, 21.5 MPa(t=0.5 ms)and 70.0, 55.0, 45.0 MPa(t=1.0 ms)and 38.0,
26.5, 39.5 MPa(t=1.5 ms)and 26.0, 19.0, 23.0 MPa(t=2.0 ms), respectively. When
the impact was on the left margo infraorbitalis orbitaeta region, the stress
values of the two points(medial left foramen rotundum, posterior clivus)reached
the peak at each time point, 8.8, 16.0 MPa(t=0.5 ms)and 10.0, 18.0 MPa(t=1.0
ms)and 5.5, 6.0 MPa(t=1.5 ms)and 11.5, 12.5 MPa(t=2.0 ms), respectively. When the
impact was on the body of left zygomatic bone, the stress values of posterior
clivus were 45.0 MPa(t=0.5 ms), 40.0 MPa(t=1.0 ms), 12.0 MPa(t=1.5 ms), 42.5
MPa(t= 2.0 ms), respectively. CONCLUSIONS: According to the difference of stress
distribution and conduction of maxillofacial and skull base bone, the speed and
the path of force transfer to the skull base were different. Finite-element
dynamic simulation can be used for the biomechanics research on maxillofacial
trauma.
PMID- 27511040
TI - [Effect of zinc ion on the expression of osteoblastic proteins in MC3T3-E1 cells
in inflammatory environment].
AB - OBJECTIVE: To investigate the effect of zinc ion on the expression of
osteoblastic proteins. METHODS: Mice osteoblasts MC3T3-E1 cells were subcultured.
Inflammatory environment model was established by tumor necrosis factor alpha(TNF
alpha)at a concentration of 10 mg/L. According to different concentration of
Zn(2+), the cells were divided into TNF-alpha group, control group, group A(TNF
alpha+10(-4) mol/L Zn(2+)), group B(TNF-alpha+10(-5) mol/L Zn(2+)), group C(TNF
alpha+10(-6) mol/L Zn(2+)). After 24, 48, and 72 h of culture, cell counting kit
8(CCK-8)assay was used to analyze the proliferation of the cells. ALP activity
was examined. Bone morphogenetic protein-2(BMP-2), Runt-related transcription
factor 2(RUNX2), Osterix and receptor activator of NF-kappaB ligand(RANKL)protein
levels were determined by Western blotting after 72 h of culture. RESULTS: The
cells grew by adherence after 24 h. After 72 h, the cells grew dense, and the
cells showed long spindle shape or irregular shape. The proliferation of
osteoblasts in TNF-alpha group, group B and group C became lower than that in the
control group(P<0.05), and was not significantly different between group A and
the control group(P >0.05). ALP activity examination demonstrated that the groups
cultured for 72 h revealed the highest ALP activity and the most prominent
differentation compared with 24 h and 48 h groups. ALP activity was significantly
decreased in TNF-alpha group, group B and group C compared with control
group(P<0.05), but was not significantly different between group A and control
group(P>0.05). The protein levels of BMP-2, RUNX2 and Osterix were significantly
decreased in TNF-alpha group, group B and group C compared with control
group(P<0.05), while showed no significant difference between group A and the
control group. Protein level of RANKL was significantly increased in TNF-alpha
group, grope B and group C compared with control group(P<0.05), while showed no
significant difference between group A and control group. CONCLUSIONS: The
concentration of 10(-4) mol/L Zn(2+) can significantly increase the expression of
osteoblastic proteins such as ALP, BMP-2, RUNX2, Osterix and decrease the
expression of RANKL in mice osteoblasts in TNF-alpha inflammatory environment.
PMID- 27511041
TI - [Effect of modification of titanium surfaces to graft poly(ethylene
glycol)methacrylate-arginine-glycine-aspartic polymer brushes on bacterial
adhesion and osteoblast cell attachment].
AB - OBJECTIVE: To study the effect of poly(ethylene glycol)methacrylate(PEG)-arginine
glycine-aspartic(RGD)polymer brushes graft on bacterial adhesion and MC3T3
osteoblast cell attachment on titanium, and to investigate if the modification of
titanium will enable the implant to be anti-fouling and promot osteointegration.
METHODS: PEG was tethered on titanium surface modified with 2-bromoisobutyryl
bromide(denoted as Ti-Br)to form Ti-PEG brushes. Functionalization of the Ti-PEG
surface with RGD was performed to form Ti-PEG-RGD brushes. The chemical
composition of modified titanium surfaces was characterized by X-ray
photoelectron spectroscopy(XPS). Changes in surface hydrophilicity and
hydrophobicity were characterized by static water contact angle measurements.
Streptococcus mutans(Sm), Actinomyces naeslundii(An)and osteoblast cell were
cultured on pure titanium(Ti), Ti-PEG, Ti-PEG-RGD surfaces respectively. There
were ten samples in each group. The bacterial adhesion ability and cell
attachment were confirmed by fluorescence microscopy and scanning electron
microscopy(SEM). RESULTS: The static water contact angle of Ti, Ti-Br, Ti-PEG, Ti
PEG-RGD was less than 10 degrees , 80 degrees , 45 degrees , 55 degrees
respectively. XPS confirmed that PEG-RGD brushes were successfully tethered on
titanium surfaces. Anti-bacterial test showed that on the pure-Ti, there were
large amount of bacteria from both groups, however, in the Ti-PEG, Ti-PEG-RGD
surfaces, both kind of bacteria were rare and distributed diffusely. Cell culture
test showed that on the Ti-PEG-RGD surfaces, the number of cells was
significantly more than that on the Ti and the Ti-PEG surfaces. CONCLUSIONS: PEG
can inhibit both kind of bacteria adhesion and osteoblast cell attachment, and
PEG-RGD brushes can not only inhibit bacterial adhesion but also promote
osteoblast cell attachment.
PMID- 27511042
TI - [Effect of three surface modification techniques of pure titanium on bacteria
adhesion and ultrasonic cleaning efficacy].
AB - OBJECTIVE: To evaluate the bacteria adhesion behavior and ultrasonic cleaning
efficacy on pure titanium modified with 3 different techiques. METHODS: Pure
titanium disks with mechanically polished surfaces(MP), titania nanotube
surfaces(TNT)and sandblast-large grit and acid-etched surfaces(SLA)were used as
substrates. The surface characteristics of the 3 types of specimens were
detected. The disks of all groups were co-cultured with Porphyromonas
gingivalis(Pg)and microcosm for 1 day and 5 days respectively. The cell
viabilities of bacteria attached to the 3 types of surfaces were tested. The
remaining bacteria on different surfaces after ultrasonic treatment were observed
through live/dead bacteria staining. RESULTS: MP and SLA surfaces demonstrated a
micro-scale structure, while TNT surfaces showed a nano-scale structure. The
surface roughness of SLA specimen was the highest([1.62 +/- 0.13]MUm), and that
of MP([0.81 +/- 0.10]MUm)and TNT specimen([0.792 +/- 0.080]MUm)were relatively
lower and showed no statistical difference(P >0.05). At 1 and 5 d, the cell
viability and the biomass of Pg attached to MP surfaces were as low as 1 829+/
210 and 13 811+/-3 110 and A570 value were 0.80+/-0.35 and 1.56+/-0.30
respectively. At 1 d, the cell viability of microcosm adhered on MP and TNT
surfaces were lower(63 943+/-6 990 and 69 860+/-5 555)than that on the SLA
surface, and the biomass of microcosm adhered on MP surfaces demonstrated the
lowest value(A570 value 5.84+/-0.60). At 5 d, both the cell viability and biomass
of micorcosm adhered on the three surfaces were of no statistical
difference(P<0.05). The remaining bacteria on TNT surfaces were the least in the
three groups and distributed sporadically after ultrasonic treatment. The
remaining bacteria on all surfaces increased with culture time. CONCLUSIONS: Both
surface topography and roughness affect early bacteria adhesion. However, this
effect can be weakened as the biofilm getting mature. The surface topography can
significantly affect the mechanical cleaning efficacy of the biofilm. TNT surface
reveals a lower adhesion of microcosm and a higher efficacy of ultrasonic
cleaning compared to MP and SLA surfaces.
PMID- 27511043
TI - [Evaluating the accuracy of three-dimensional reconstruction of the intercuspal
position for dentition casts aided by a mechanical appliance].
AB - OBJECTIVE: To develop a aided mechanical appliance for rapid reconstruction of
three-dimensional(3D)relationship of dentition model after scanning and
evaluation of its accuracy. METHODS: The appliance was designed by forward
engineering software and fabricated by a high precision computer numerical
control(CNC)system. It contained upper and lower body, magnetic pedestal and
three pillars. Nine 3 mm diameter hemispheres were distributed equally on the
axial surface of each pedestal. Faro Edge 1.8m was used to directly obtain center
of each hemisphere(contact method), defined as known center. A pair of die-stone
standard dentition model were fixed in intercuspal position and then fixed on the
magnetic pedestals with low expansion ratio plaster. Activity 880 dental scanner
was used to scan casts after the plaster was completely set. In Geomagic 2012,
the centers of each hemisphere were fitted and defined as scanning centers.
Scanning centers were aligned to known centers by reference point system to
finish the 3D reconstruction of the intercuspal occlusion for the dentition
casts. An observation coordinate system was interactively established. The
straight-line distances in the X(coronal), Y(saggital), and Z(vertical)between
the remaining 6 pairs of center points derived from contact method and fitting
method were measured respectively and analyzed using a paired t-test. RESULTS:
The differences of the straight-line distances of the remaining 6 pairs of center
points between the two methods were X:(-0.05+/-0.10)mm, Y:(0.02+/-0.06)mm, and
Z:(0.01 +/- 0.05)mm. The results of paired t-test showed no significant
differences(P>0.05). CONCLUSIONS: The mechanical appliance can help to
reconstruct 3D jaw relation by scanning single upper and lower dentition model
with usual commercial available dental cast scanning system.
PMID- 27511044
TI - [The reliability of electrochemical enzyme-linked immunosorbent assay for
detection of dentin sialophosphoprotein in gingival crevicular fluid].
AB - OBJECTIVE: To investigate the reliability of electrochemical enzyme-linked
immunosorbent assay(ELISA)for the detection of dentin sialophosphoprotein(DSPP)in
gingival crevicular fluid(GCF)of orthodontic patients. METHODS: GCF were
collected from the orthodontic patients, and then the amount of DSPP in GCF were
detected by electrochemical ELISA and spectroscopic ELISA respectively. The
difference between the results of two methods were analyzed. RESULTS: In
electrochemical ELISA, the second order derivative linear sweep voltammetric peak
current was linear with DSPP concentration in the range from 0.25-800.00 ng/L. It
was found that the detection limit of the electrochemical method(0.25 ng/L)was
much lower than that of the spectroscopic method. The paired-samples rank sum
test showed no significant difference between the DSPP concentrations in human
GCF samples measured by spectroscopic ELISA procedure and those measured by
electrochemical ELISA procedure(P=0.063). CONCLUSIONS: Electrochemical ELISA is a
viable way of detecting DSPP in GCF with higher sensitivity than spectroscopic
ELISA.
PMID- 27511045
TI - [The historical materials of stomatology in the All Things, Prescriptions of
Fifty-two Diseases and Yinshu].
AB - All Things, Prescriptions of Fifty-two Diseases and Yinshu were three bamboo and
silk medical manuscripts which form-time was no later than the late Warring
States period. From the visible bamboo and silk, the ancient Chinese knew the
relationships between some drugs and the volume of saliva and used compound drugs
to treat dental caries. Some oral and maxillofacial diseases, such as
inflammation and pain of oromaxillo-facial region, temporomandibular dislocation
and the methods of treatment were descriped in these books. Mouth-rinsing and
tooth-picking were the more often used methods for maintaining oral hygiene.
Kouchi(clicking the tooth)was also used for prevention and/or treatment of
caries. Most of these knowledge were the first documents in ancient China.
PMID- 27511046
TI - Intervention not always necessary in post-appendectomy abscesses in children;
clinical experience in a tertiary surgical centre and an overview of the
literature.
AB - This study aims to provide an overview of both our own experience and the
available literature on the treatment of post-appendectomy abscess (PAA) in
children. We performed a historical cohort study encompassing all children aged 0
17 years old treated for a radiologically confirmed PAA between 2007 and 2013.
Their medical charts were reviewed and descriptive analyses were performed. A
literature search on the treatment of PAA in children was performed. In our
cohort, 25 out of 372 (7 %) children developed a PAA. Thirteen were treated with
a noninvasive strategy and 12 with an invasive strategy (percutaneous or surgical
drainage). The immediate success rate was 9/13 (69 %) and 8/12 (67 %) for the
noninvasive and invasive strategy, respectively. In both groups, four children
(31 and 33 % resp.) required delayed interventions after their initial treatment.
In the literature review, six studies were included which reported a median
(range) frequency of persistent or recurrent abscess of 9 % (0-30 %), 50 % (0-100
%) and 24 % (0-33 %) for the antibiotic (noninvasive), percutaneous drainage
(invasive) and surgical drainage strategies, respectively. CONCLUSION: Although
confounding by indication cannot be excluded, we recommend noninvasive treatment
as a safe strategy for PAA in children with stable condition. WHAT IS KNOWN: *
Post-appendectomy abscess is a well-known and feared complication, occurring in
up to 24 % of the children treated surgically for appendicitis. * Several
strategies are available to treat this condition, all with advantages and
disadvantages. What is new: * Noninvasive strategy is a safe strategy for
children with a PAA in a stable condition. * An overview of the literature (the
first to our knowledge) supports the above-mentioned statement.
PMID- 27511047
TI - Predicting Motor Sequence Learning in Individuals With Chronic Stroke.
AB - BACKGROUND: Conventionally, change in motor performance is quantified with
discrete measures of behavior taken pre- and postpractice. As a high degree of
movement variability exists in motor performance after stroke, pre- and
posttesting of motor skill may lack sensitivity to predict potential for motor
recovery. OBJECTIVE: Evaluate the use of predictive models of motor learning
based on individual performance curves and clinical characteristics of motor
function in individuals with stroke. METHODS: Ten healthy and fourteen
individuals with chronic stroke performed a continuous joystick-based tracking
task over 6 days, and at a 24-hour delayed retention test, to assess implicit
motor sequence learning. RESULTS: Individuals with chronic stroke demonstrated
significantly slower rates of improvements in implicit sequence-specific motor
performance compared with a healthy control (HC) group when root mean squared
error performance data were fit to an exponential function. The HC group showed a
positive relationship between a faster rate of change in implicit sequence
specific motor performance during practice and superior performance at the
delayed retention test. The same relationship was shown for individuals with
stroke only after accounting for overall motor function by including Wolf Motor
Function Test rate in our model. CONCLUSION: Nonlinear information extracted from
multiple time points across practice, specifically the rate of motor skill
acquisition during practice, relates strongly with changes in motor behavior at
the retention test following practice and could be used to predict optimal doses
of practice on an individual basis.
PMID- 27511048
TI - Small-World Characteristics of Cortical Connectivity Changes in Acute Stroke.
AB - Background After cerebral ischemia, disruption and subsequent reorganization of
functional connections occur both locally and remote to the lesion. Recently,
complexity of brain connectivity has been described using graph theory, a
mathematical approach that depicts important properties of complex systems by
quantifying topologies of network representations. Functional and dynamic changes
of brain connectivity can be reliably analyzed via electroencephalography (EEG)
recordings even when they are not yet reflected in structural changes of
connections. Objective We tested whether and how ischemic stroke in the acute
stage may determine changes in small-worldness of cortical networks as measured
by cortical sources of EEG. Methods Graph characteristics of EEG of 30
consecutive stroke patients in acute stage (no more than 5 days after the event)
were examined. Connectivity analysis was performed using eLORETA in both
hemispheres. Results Network rearrangements were mainly detected in delta, theta,
and alpha bands when patients were compared with healthy subjects. In delta and
alpha bands similar findings were observed in both hemispheres regardless of the
side of ischemic lesion: bilaterally decreased small-worldness in the delta band
and bilaterally increased small-worldness in the alpha2 band. In the theta band,
bilaterally decreased small-worldness was observed only in patients with stroke
in the left hemisphere. Conclusions After an acute stroke, brain cortex
rearranges its network connections diffusely, in a frequency-dependent modality
probably in order to face the new anatomical and functional frame.
PMID- 27511049
TI - Saline versus balanced solutions: are clinical trials comparing two crystalloid
solutions really needed?
PMID- 27511050
TI - The study on mechanism of the modified Chinese herbal compound, jianpijiedu, on a
mouse model of hepatic carcinoma cachexia.
AB - Various studies have investigated hepatic carcinoma cachexia, however, there is
little published information regarding the effect of Chinese Medicine carcinoma
cachexia. The present study was performed to investigate the effect of modified
Chinese herbal compound jianpijiedu (MJPJD) on a mouse model of ascites-induced
hepatic carcinoma cachexia. C57BL/6 mice were randomized to five groups: Control
(Group A); xenograft tumor (Group B); low concentration of MJPJD (Group C); high
concentration of MJPJD (Group D) and medroxyprogesterone (MPA) combined with
indometacin (IND; Group E). The mouse model of ascites-induced hepatic carcinoma
cachexia was established by abdominal injection of H22 hepatic carcinoma cells.
Subsequently, the body weight, food intake and gastrocnemius weight were
recorded, and the levels of interleukin (IL)-lalpha, IL-6, tumor necrosis factor
alpha (TNF-alpha) in ascites were detected by enzyme-linked immunosorbent assay.
The protein expression levels of muscle RING-finger protein-1 (MU-RF1) and
atrogin 1 were detected by western blotting and immunohistochemistry, and the
mRNA levels in gastrocnemius were detected by reverse transcription-quantitative
polymerase chain reaction. Compared with the xenograft tumor group, the
administration of MJPJD inhibited the increase in body weight and the volume of
ascites, the consumption of gastrocnemius was reduced, the net weight of ascites
was maintained, the food intake was enhanced and the levels of the cytokines IL
lalpha, IL-6, TNF-alpha in ascites and the levels of MU-RF1 and atrogin 1
proteins were reduced. These results indicated that MJPJD delays the pathological
process of ascites-induced hepatic carcinoma cachexia, and the mechanism of
action may be correlated with a reduction in the levels of IL-lalpha, IL-6, TNF
alpha and inhibiting the activation of the ubiquitin proteosome pathway.
PMID- 27511051
TI - Integrating gross pathology into teaching of undergraduate medical science
students using human cadavers.
AB - Human cadavers offer a great opportunity for histopathology students for the
learning and teaching of tissue pathology. In this study, we aimed to implement
an integrated learning approach by using cadavers to enhance students' knowledge
and to develop their skills in gross tissue identification, handling and
dissection techniques. A total of 35 students enrolled in the undergraduate
medical science program participated in this study. A 3-hour laboratory session
was conducted that included an active exploration of cadaveric specimens to
identify normal and pathological tissues as well as tissue dissection. The
majority of the students strongly agreed that the integration of normal and
morbid anatomy improved their understanding of tissue pathology. All the students
either agreed or strongly agreed that this laboratory session was useful to
improve their tissue dissection and instrument handling skills. Furthermore,
students from both cohorts rated the session as very relevant to their learning
and recommended that this approach be added to the existing histopathology
curriculum. To conclude, an integrated cadaver-based practical session can be
used effectively to enhance the learning experience of histopathology science
students, as well as improving their manual skills of tissue treatment,
instrument handling and dissection.
PMID- 27511052
TI - Hormesis, mithridatism and Paracelsus: A little oxidative stress goes a long way.
PMID- 27511053
TI - Adherence to the Mediterranean diet is associated with reduced risk of incident
chronic kidney diseases among Tehranian adults.
AB - Greater adherence to the Mediterranean diet has beneficial effects on the
prevention of chronic diseases. In the current study, we investigated the
association between the Mediterranean diet score (MDS) and the 6-year incidence
of chronic kidney disease (CKD), conducted in the framework of the Tehran Lipid
and Glucose Study with 1212 adults, aged 30-71 years. Dietary intake was assessed
using a valid and reliable food-frequency questionnaire, and all subjects
received scores between 0 and 8 points based on the traditional MDS. The
components of the MDS were fruits and nuts, vegetables, legumes, cereals, fish,
meat, dairy products and the monounsaturated to saturated fatty acid ratio. The
odds ratio (OR) for the occurrence of CKD according to the quartiles of the MDS
was assessed by multivariable logistic regression. The mean (s.d.) age of
participants (51% male) at baseline was 43.5 (9.4) years. The median (25-75
interquartile range) of MDS for all subjects was 4 (3-5).The incidence of CKD was
19%. After adjustment for all potential confounding variables, individuals in the
highest quartile of the MDS were 51% less likely to have CKD than those in the
lowest quartile (OR=0.49; 95% confidence interval (CI): 0.30-0.82). Additionally,
after further adjustment for baseline estimated glomerular filtration rate (GFR),
the inverse association between the MDS and the 6-year incidence of CKD remained
significant (OR=0.53; 95% CI: 0.31-0.91). Our findings demonstrate a significant
inverse association between the MDS and the risk of incident CKD, indicating that
adherence to the Mediterranean diet has favorable effects on the prevention of
kidney dysfunction.
PMID- 27511054
TI - Increased cardiovascular risk of treated white coat and masked hypertension in
patients with diabetes and chronic kidney disease: the HONEST Study.
AB - The prognostic implications of treated white coat hypertension (WCH) and masked
hypertension (MH) in patients with diabetes mellitus (DM) or chronic kidney
disease (CKD) are not well documented. Using data from the HONEST study (n=21
591), we investigated the relationships between morning home systolic blood
pressure (MHSBP) or clinic systolic blood pressure (CSBP) and cardiovascular (CV)
risk in hypertensive patients with and without DM or CKD receiving olmesartan
based antihypertensive therapy. The study included 4426 DM patients and 4346 CKD
patients at baseline who had 101 and 87 major CV events, respectively, during the
follow-up. Compared with well-controlled non-DM patients (MHSBP <135 mm Hg; CSBP
<140 mm Hg), DM patients with WCH (MHSBP <135 mm Hg; CSBP ?140 mm Hg), MH (MHSBP
?135 mm Hg; CSBP <140 mm Hg) or poorly controlled hypertension (PCH) (MHSBP ?135
mm Hg; CSBP ?140 mm Hg) had significantly higher CV risk (hazard ratio (HR),
2.73, 2.77 and 2.81, respectively). CV risk was also significantly increased in
CKD patients with WCH, MH and PCH (HR, 2.14, 1.70 and 2.20, respectively)
compared with well-controlled non-CKD patients. Furthermore, DM patients had
significantly higher incidence rate than non-DM patients of MHSBP ?125 to <135 mm
Hg (HR, 1.98) and ?135 to <145 mm Hg (HR, 2.41). In conclusion, both WCH and MH
are associated with increased CV risk, and thus control of both MHSBP and CSBP is
important to reduce CV risk in DM or CKD patients. The results also suggest that
even lower MHSBP (<125 mm Hg) may be beneficial for DM patients, although this
conclusion is limited by the small number of patients.
PMID- 27511055
TI - Mesenchymal-to-epithelial transition in the placental tissues of patients with
preeclampsia.
AB - During early pregnancy in humans, mesenchymal-to-epithelial transition (MET)
contributes to decidualization of endometrial stromal cells in the uterus.
Defects in decidualization can interfere with placental formation and can lead to
pregnancy complications, including preeclampsia. However, MET markers in
preeclamptic placental tissues have not been characterized. To investigate the
association between changes in MET and preeclampsia, we evaluated MET markers in
preeclamptic placental tissues relative to normal placentas. Placentas were
collected from 20 preeclamptic and 20 normotensive healthy women. Protein and
mRNA levels of MET-related markers, including E-cadherin, N-cadherin (neural
cadherin), vimentin, ZO-1 (zona occludens 1) and SLUG, were analyzed via western
blot and quantitative real-time PCR (Q-PCR), respectively. E- and N-cadherin were
localized in the placentas through immunohistochemistry. The mRNA and protein
expressions of GLI1 and GLI2 were detected by Q-PCR and western blot. In
preeclamptic placentas, the mRNA and protein levels of E-cadherin and ZO-1 were
elevated relative to the controls, whereas the levels of N-cadherin, SLUG and
vimentin were lower. The staining intensities of E- and N-cadherin were
consistent with their protein levels detected by western blot. The mRNA and
protein levels of GLI1 and GLI2 were significantly lower in preeclamptic
placentas compared with that in control placentas. We conclude that MET in the
placenta may be associated with the progression of preeclampsia.
PMID- 27511056
TI - Treatment of Inappropriate Sexual Behavior in Dementia.
AB - OPINION STATEMENT: Inappropriate sexual behavior (ISB) is a relatively common and
potentially disruptive form of behavior in people with dementia. It can cause
considerable distress and put placements and people at risk. Yet it is poorly
researched and understood. In addition to non-pharmacological approaches to
management, a wide range of classes of medication has been used in ISB, and the
results have been reported as single cases or short series, though none has been
the subject of a randomized clinical trial, in part because of the lack of a well
defined method of observing and measuring ISB, as well as the significant ethical
considerations. Pharmacological treatments for which there is low-level evidence
of efficacy in the literature include antidepressants, antipsychotics,
anticonvulsants, cholinesterase inhibitors, hormonal agents, and beta-blockers.
None of the drugs discussed here is licensed for use in ISB, and elderly people,
particularly those with dementia, are at high risk of adverse effects. Caution is
advised before using medication in this group of people. It is important to
consider alternative non-pharmacological treatments, as well as discussing issues
of ethics and consent with those involved, before initiating treatment. It is
helpful to identify and monitor target symptoms. Pharmacological treatments
should be started at low dose and titrated up slowly and carefully. Nevertheless,
in some situations, medication may provide a useful part of a management plan for
ISB.
PMID- 27511057
TI - Three cases of tubulointerstitial nephritis and uveitis syndrome with different
clinical manifestations.
AB - We here describe three different clinical manifestations of tubulointerstitial
nephritis and uveitis (TINU) syndrome. We examined and diagnosed the following 3
patients: a 15-year-old boy with bilateral anterior uveitis (Case 1), a 14-year
old girl with bilateral papilledema (Case 2), and a 49-year-old woman with
panuveitis (Case 3). The findings are presented herein. Case 1: The patient had
bilateral anterior uveitis. Urinalysis revealed markedly increased beta2
microglobulin and N-acetyl-beta-D-glucosaminidase levels. As the patient was
pathologically diagnosed with tubulointerstitial nephritis (TIN), we diagnosed
TINU based on the presence of both uveitis and TIN. He was treated with oral
corticosteroids. Case 2: This patient showed anterior uveitis and papilledema in
both eyes. On initial examination, the urine test results did not show any
abnormality. Three months later, high beta2-microglobulin and N-acetyl-beta-D
glucosaminidase levels were detected. As the patient was clinically diagnosed
with TIN, we subsequently diagnosed TINU. Both the ocular and renal findings
improved without treatment. Case 3: The patient developed bilateral panuveitis,
retinal vasculitis, and macular edema, which were initially suspected to be
sarcoidosis. However, she was pathologically diagnosed with TIN 12 months before
the onset of uveitis; therefore, she was finally diagnosed with TINU. She
recovered with local corticosteroid administration only. TINU may present with
fundal features in addition to anterior uveitis. Detailed history taking and
urinalysis are important to determine the presence of tubular disorders in
similar patients.
PMID- 27511058
TI - Modulation of postprandial lipaemia by a single meal containing a commonly
consumed interesterified palmitic acid-rich fat blend compared to a non
interesterified equivalent.
AB - PURPOSE: Interesterification of palm stearin and palm kernal (PSt/PK) is widely
used by the food industry to create fats with desirable functional
characteristics for applications in spreads and bakery products, negating the
need for trans fatty acids. Previous studies have reported reduced postprandial
lipaemia, an independent risk factor for CVD, following interesterified (IE)
palmitic and stearic acid-rich fats that are not currently widely used by the
food industry. The current study investigates the effect of the most commonly
consumed PSt/PK IE blend on postprandial lipaemia. METHODS: A randomised,
controlled, crossover (1 week washout) double-blind design study (n = 12 healthy
males, 18-45 years), compared the postprandial (0-4 h) effects of meals
containing 50 g fat [PSt/PK (80:20); IE vs. non-IE] on changes in plasma
triacylglycerol (TAG), glucose, glucose-dependent insulinotropic polypeptide
(GIP), peptide YY (PYY), insulin, gastric emptying (paracetamol concentrations)
and satiety (visual analogue scales). RESULTS: The postprandial increase in
plasma TAG was higher following the IE PSt/PK versus the non-IE PSt/PK, with a 51
% greater incremental area under the curve [mean difference with 95 % CI 41 (23,
58) mmol/L min P = 0.001]. The pattern of lipaemia was different between meals;
at 4-h plasma TAG concentrations declined following the IE fat but continued to
rise following the non-IE fat. Insulin, glucose, paracetamol, PYY and GIP
concentrations increased significantly after the test meals (time effect; P <
0.001 for all), but did not differ between test meals. Feelings of fullness were
higher following the non-IE PSt/PK meal (diet effect; P = 0.034). No other
significant differences were noted. CONCLUSIONS: Interesterification of PSt/PK
increases early phase postprandial lipaemia (0-4 h); however, further
investigation during the late postprandial phase (4-8 h) is warranted to
determine the rate of return to baseline values. TRIAL REGISTRATION NUMBER:
Clinicaltrials.gov as NCT02365987.
PMID- 27511060
TI - High performance flexible double-sided micro-supercapacitors with an organic gel
electrolyte containing a redox-active additive.
AB - In this study, we report the fabrication of a high performance flexible micro
supercapacitor (MSC) with an organic gel electrolyte containing a redox-active
additive, referred to as poly(methyl methacrylate)-propylene carbonate-lithium
perchlorate-hydroquinone (PMMA-PC-LiClO4-HQ). Hexagonal MSCs fabricated on thin
polyethylene terephthalate (PET) films had interdigitated electrodes made of
spray-coated multi-walled carbon nanotubes (MWNTs) on Au. The addition of HQ as a
redox-active additive enhanced not only the specific capacitance but also the
energy density of the MSCs dramatically, which is approximately 35 times higher
than that of MSCs without the HQ additive. In addition, both areal capacitance
and areal energy density could be doubled by fabrication of double-sided MSCs,
where two MSCs are connected in parallel. The double-sided MSCs exhibited stable
electrochemical performance during repeated deformation by bending. By dry
transferring the double-sided MSCs based on PMMA-PC-LiClO4-HQ on a deformable
polymer substrate, we fabricated a stretchable MSC array, which also retained its
electrochemical performance during a uniaxial strain of 40%. Furthermore, a
wearable energy storage bracelet made of such an MSC array could operate a MU-LED
on the wrist.
PMID- 27511059
TI - New pregnane and phenolic glycosides from Solenostemma argel.
AB - From the aerial parts, pericarps and roots of Solenostemma argel, three new
pregnane glycosides (1-3) with two known ones and a new phenolic glycoside (4)
have been isolated. Their structures were established by extensive 1D - and 2D
NMR and mass spectroscopic analysis. The cytotoxicity of all compounds was
evaluated against two human tumor cell lines (SW 480, MCF-7), but none of them
was active in the concentration range 0.9-59.0MUM. Compounds 2 and the known
argeloside F at non toxic concentrations for the PBMCs (27.3MUM and 27.6MUM,
respectively) significantly decreased the Il-1beta production by LPS-stimulated
PBMCs. All isolated compounds showed a significant antioxidant potential with
ORAC values in the concentration range 3481-9617MUmoleq. Trolox/100g.
PMID- 27511061
TI - Impact of leptin on memory function and hippocampal structure in mild cognitive
impairment.
AB - Metabolic changes have been suggested to contribute to dementia and its precursor
mild cognitive impairment (MCI), yet previous results particularly for the
"satiety hormone" leptin are mixed. Therefore, we aimed to determine if MCI
patients show systematic differences in leptin, independent of sex, adipose mass,
age, and glucose and lipid metabolism, and whether leptin levels correlated with
memory performance and hippocampal integrity. Forty MCI patients (20 females,
aged 67 years +/- 7 SD) were compared to 40 healthy controls (HC) that were pair
wise matched for sex, age, and body fat. Memory performance was assessed using
the auditory verbal learning test. Volume and microstructure of the hippocampus
were determined using 3T-neuroimaging. Fasting serum markers of leptin, glucose
and lipid metabolism, and other confounding factors were assayed. MCI patients,
compared with HC, showed lower serum leptin, independent of sex, age, and body
fat (P < 0.001). Glucose and lipid markers did not attenuate these results.
Moreover, MCI patients exhibited poorer memory and lower volume and
microstructural integrity within hippocampal subfields. While leptin and memory
were not significantly correlated, mediation analyses indicated that lower leptin
contributed to poorer memory through its negative effect on right hippocampus
volume and left hippocampus microstructure. We demonstrated that MCI is
associated with lower serum leptin independent of sex, age, body fat, glucose,
and lipid metabolism. Our data further suggest that inefficient leptin signaling
could partly contribute to decreases in memory performance through changes in
hippocampus structure, a hypothesis that should now be verified in longitudinal
studies. Hum Brain Mapp 37:4539-4549, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27511062
TI - The master female triathlete.
AB - The world of triathlon has expanded to include all ages and both sexes. One of
the largest growing age groups is the master female athlete. It is important for
the physical therapist to understand the special needs of this population in
order to adequately care for master female athletes so they can participate at a
high level and injury-free. Biology of aging, injury prevention and a suggested
training program are presented in this Masterclass article.
PMID- 27511063
TI - Generalized optimal design for two-arm, randomized phase II clinical trials with
endpoints from the exponential dispersion family.
AB - For two-arm randomized phase II clinical trials, previous literature proposed an
optimal design that minimizes the total sample sizes subject to multiple
constraints on the standard errors of the estimated event rates and their
difference. The original design is limited to trials with dichotomous endpoints.
This paper extends the original approach to be applicable to phase II clinical
trials with endpoints from the exponential dispersion family distributions. The
proposed optimal design minimizes the total sample sizes needed to provide
estimates of population means of both arms and their difference with pre
specified precision. Its applications on data from specific distribution families
are discussed under multiple design considerations. Copyright (c) 2016 John Wiley
& Sons, Ltd.
PMID- 27511065
TI - The cellular mechanisms that maintain neuronal polarity.
AB - As polarized cells, neurons maintain different sets of resident plasma membrane
proteins in their axons and dendrites, which is consistent with the different
roles that these neurites have in electrochemical signalling. Axonal and
dendritic proteins are synthesized together within the somatodendritic domain;
this raises a fundamental question: what is the nature of the intracellular
trafficking machinery that ensures that these proteins reach the correct domain?
Recent studies have advanced our understanding of the processes underlying the
selective sorting and selective transport of axonal and dendritic proteins and
have created potential avenues for future progress.
PMID- 27511066
TI - Bile acid receptor TGR5, NADPH Oxidase NOX5-S and CREB Mediate Bile Acid-Induced
DNA Damage In Barrett's Esophageal Adenocarcinoma Cells.
AB - The mechanisms whereby bile acid reflux may accelerate the progression from
Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully
understood. In this study we found that bile acid taurodeoxycholic acid (TDCA)
significantly increased the tail moment (TM) and histone H2AX phosphorylation in
FLO-1 EA cells, an increase which was significantly decreased by knockdown of
TGR5. Overexpression of TGR5 significantly increased TDCA-induced TM increase and
H2AX phosphorylation. In addition, NADPH oxidase inhibitor diphenylene iodonium
significantly inhibited the TDCA-induced increase in TM and H2AX phosphorylation.
TDCA-induced increase in TM and H2AX phosphorylation was significantly decreased
by knockdown of NOX5-S and overexpression of NOX5-S significantly increased TDCA
induced increase in the tail moment and H2AX phosphorylation. Furthermore, TDCA
significantly increased cAMP response element binding protein (CREB)
phosphorylation in FLO-1 cells. Knockdown of CREB significantly decreased TDCA
induced increase in NOX5-S mRNA and the tail moment. Conversely, overexpression
of CREB significantly increased TDCA-induced TM increase. We conclude that TDCA
induced DNA damage may depend on the activation of TGR5, CREB and NOX5-S. It is
possible that in Barrett's patients bile acids may activate NOX5-S and increase
reactive oxygen species (ROS) production via activation of TGR5 and CREB. NOX5-S
derived ROS may cause DNA damage, thereby contributing to the progression from BE
to EA.
PMID- 27511103
TI - Synchronizing Watches: The Challenge of Aligning Implementation Science and
Public Systems.
AB - This special issue of Administration and Policy in Mental Health explores the
complexities of the outer system context in implementation science research. In
this commentary, we highlight areas of asynchrony between implementation science
research and policy realities of public systems. Timing is a critical factor for
many aspects of system-level implementation including when and how evidence-based
practice initiatives are launched, short and inconsistent timeframes for funding
and support, need for early indicators of success and demonstrating return on
investment. Greater consideration for the timing that drives change in public
systems will strengthen efforts to implement and sustain EBPs in community
settings.
PMID- 27511067
TI - Blood pressure variability and cardiovascular disease: systematic review and meta
analysis.
AB - OBJECTIVE: To systematically review studies quantifying the associations of long
term (clinic), mid-term (home), and short term (ambulatory) variability in blood
pressure, independent of mean blood pressure, with cardiovascular disease events
and mortality. DATA SOURCES: Medline, Embase, Cinahl, and Web of Science,
searched to 15 February 2016 for full text articles in English. ELIGIBILITY
CRITERIA FOR STUDY SELECTION: Prospective cohort studies or clinical trials in
adults, except those in patients receiving haemodialysis, where the condition may
directly impact blood pressure variability. Standardised hazard ratios were
extracted and, if there was little risk of confounding, combined using random
effects meta-analysis in main analyses. Outcomes included all cause and
cardiovascular disease mortality and cardiovascular disease events. Measures of
variability included standard deviation, coefficient of variation, variation
independent of mean, and average real variability, but not night dipping or day
night variation. RESULTS: 41 papers representing 19 observational cohort studies
and 17 clinical trial cohorts, comprising 46 separate analyses were identified.
Long term variability in blood pressure was studied in 24 papers, mid-term in
four, and short-term in 15 (two studied both long term and short term
variability). Results from 23 analyses were excluded from main analyses owing to
high risks of confounding. Increased long term variability in systolic blood
pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95%
confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09
to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart
disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term
and short term variability in daytime systolic blood pressure were also
associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16,
respectively). CONCLUSIONS: Long term variability in blood pressure is
associated with cardiovascular and mortality outcomes, over and above the effect
of mean blood pressure. Associations are similar in magnitude to those of
cholesterol measures with cardiovascular disease. Limited data for mid-term and
short term variability showed similar associations. Future work should focus on
the clinical implications of assessment of variability in blood pressure and
avoid the common confounding pitfalls observed to date. SYSTEMATIC REVIEW
REGISTRATION: PROSPERO CRD42014015695.
PMID- 27511104
TI - [Not Available].
PMID- 27511106
TI - Case of severe acneiform eruptions associated with the BRAF inhibitor
vemurafenib.
PMID- 27511105
TI - Administration of prostacyclin modulates cutaneous blood flow but not sweating in
young and older males: roles for nitric oxide and calcium-activated potassium
channels.
AB - KEY POINTS: In young adults, cyclooxygenase (COX) contributes to the heat loss
responses of cutaneous vasodilatation and sweating, and this may be mediated by
prostacyclin-induced activation of nitric oxide synthase (NOS) and calcium
activated potassium (KCa) channels. This prostacyclin-induced response may be
diminished in older relative to young adults because ageing is known to attenuate
COX-dependent heat loss responses. We observed that, although prostacyclin does
not mediate sweating in young and older males, it does modulate cutaneous
vasodilatation, although the magnitude of increase is similar between groups. We
also found that, although NOS and KCa channels contribute to prostacyclin-induced
cutaneous vasodilatation in young males, these contributions are diminished in
older males. Our findings provide new insight into the mechanisms governing heat
loss responses and suggest that the age-related diminished COX-dependent heat
loss responses reported in previous studies may be a result of the reduced COX
derived production of prostanoids (e.g., prostacyclin) rather than the decreased
sensitivity of prostanoid receptors. ABSTRACT: Cyclooxygenase (COX) contributes
to the regulation of cutaneous vasodilatation and sweating; however, the
mechanism(s) underpinning this response remain unresolved. We hypothesized that
prostacyclin (a COX-derived product) may directly mediate cutaneous
vasodilatation and sweating through nitric oxide synthase (NOS) and calcium
activated potassium (KCa) channels in young adults. However, these responses
would be diminished in older adults because ageing attenuates COX-dependent
cutaneous vasodilatation and sweating. In young (25 +/- 4 years) and older (60 +/
6 years) males (nine per group), cutaneous vascular conductance (CVC) and sweat
rate were evaluated at four intradermal forearm skin sites: (i) control; (ii) 10
mm NG -nitro-l-arginine (l-NNA), a non-specific NOS inhibitor; (iii) 50 mm
tetraethylammonium (TEA), a non-specific KCa channel blocker; and (iv) 10 mm l
NNA + 50 mm TEA. All four sites were coadministered with prostacyclin in an
incremental manner (0.04, 0.4, 4, 40 and 400 MUm each for 25 min). Prostacyclin
induced increases in CVC were similar between groups (all concentrations, P >
0.05). l-NNA and TEA, as well as their combination, lowered CVC in young males at
all prostacyclin concentrations (P <= 0.05), with the exception of l-NNA at 0.04
MUm (P > 0.05). In older males, CVC during prostacyclin administration was not
influenced by l-NNA (all concentrations), TEA (4-400 MUm) or their combination
(400 MUm) (P > 0.05). No effect on sweat rate was observed in either group (all
concentrations, P > 0.05). We conclude that, although prostacyclin does not
mediate sweating, it modulates cutaneous vasodilatation to a similar extent in
young and older males. Furthermore, although NOS and KCa channels contribute to
the prostacyclin-induced cutaneous vasodilatation in young males, these
contributions are diminished in older males.
PMID- 27511107
TI - Salt secretion is linked to acid-base regulation of ionocytes in seawater
acclimated medaka: new insights into the salt-secreting mechanism.
AB - Ionocytes in the skin and gills of seawater (SW) teleosts are responsible for
both salt and acid secretion. However, the mechanism through which ionocytes
secrete acid is still unclear. Here, we hypothesized that apical Na(+)/H(+)
exchangers (NHE2/3), carbonic anhydrase (CA2-like), and basolateral HCO3(-)/Cl(-)
exchanger (AE1) are involved in acid secretion. In addition, the hypothesized
involvement of basolateral AE1 suggested that acid secretion may be linked to Cl(
) secretion by ionocytes. The scanning ion-selective electrode technique (SIET)
was used to measure H(+) and Cl(-) secretion by ionocytes in the skin of medaka
larvae acclimated to SW. Treatment with inhibitors of NHE, CA, and AE suppressed
both H(+) and Cl(-) secretion by ionocytes. Short-term exposure to hypercapnic SW
stimulated both H(+) and Cl(-) secretion. mRNA of CA2-like and AE1 were localized
to ionocytes in the skin. Branchial mRNA levels of NKCC1a, CA2-like, and AE1a
increased together with the salinity to which fish were acclimated. In addition,
both AE1a and AE1b mRNA increased in fish acclimated to acidified (pH 7) SW;
NKCC1a mRNA increased in fish acclimated to pH 9 SW. This study reveals the
mechanism of H(+) secretion by ionocytes, and refines our understanding of the
well-established mechanism of Cl(-) secretion by ionocytes of SW fish.
PMID- 27511108
TI - Leucine Zipper-bearing Kinase promotes axon growth in mammalian central nervous
system neurons.
AB - Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage
kinase family with high sequence identity to Dual Leucine Zipper Kinase
(DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to
injury, the role of LZK in mammalian neurons is poorly understood. By gain- and
loss-of-function analyses in neuronal cultures, we identify LZK as a novel
positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs
among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity
positively regulating LZK protein levels. Neuronal maturation or activity
deprivation activates the LZK-MKK4-JNK pathway. LZK and DLK share commonalities
in signaling, regulation, and effects on axon extension. Furthermore, LZK
dependent regulation of DLK protein expression and the lack of additive effects
on axon growth upon co-manipulation suggest complex functional interaction and
cross-regulation between these two kinases. Together, our data support the
possibility for two structurally related MAP3Ks to work in concert to mediate
axonal responses to external insult or injury in mammalian CNS neurons.
PMID- 27511109
TI - Postpartum psychiatric emergency visits: a nested case-control study.
AB - Mental health conditions are one of the most common reasons for postpartum
emergency department (ED) visits. Characteristics of women using the ED and their
mental health service use before presentation are unknown. We characterized all
women in Ontario, Canada (2006-2012), who delivered a live born infant and had a
psychiatric ED visit within 1 year postpartum (n = 8728). We compared those whose
ED visit was the first physician mental health contact since delivery to those
who had accessed mental health services on specific indicators of marginalization
hypothesized to be associated with lower likelihood of mental health contact
prior to the ED visit. For 60.4 % of women, this was the first physician mental
health contact since delivery. The majority were presenting with a mood or
anxiety disorder, and only 13.6 % required hospital admission. These women were
more likely to have material deprivation and residential instability than women
with contact (Q5 vs. Q1 aORs 1.30, 95 % CI 1.12-1.50; 1.17, 95 % CI 1.01-1.36),
to live in rural vs. urban areas (aOR 1.58, 95 % CI 1.38-1.80), and to be low vs.
high income quintile (aOR 1.18, 95 % CI 1.01-1.38). The frequent use of ED
services as the first point of contact for mental health concerns suggests that
interventions to improve timely and equitable access to effective outpatient
postpartum mental health care are needed. Marginalized women are at particularly
high risk of not having accessed outpatient services prior to an ED visit, and
therefore, future research and interventions will specifically need to consider
the needs of this group.
PMID- 27511110
TI - Risk of false positive results to SARM S-4 in case of therapeutic use of
antineoplastic/antiandrogen drug containing flutamide: a case study.
PMID- 27511111
TI - Study of the Transformations of Micro/Nano-crystalline Acetaminophen Polymorphs
in Drug-Polymer Binary Mixtures.
AB - This study elucidates the physical properties of sono-crystallised micro/nano
sized acetaminophen/paracetamol (PMOL) and monitors its possible transformation
from polymorphic form I (monoclinic) to form II (orthorhombic). Hydrophilic
Plasdone(r) S630 copovidone (S630), N-vinyl-2-pyrrolidone and vinyl acetate
copolymer, and methacrylate-based cationic copolymer, Eudragit(r) EPO (EPO), were
used as polymeric carriers to prepare drug/polymer binary mixtures. Commercially
available PMOL was crystallised under ultra sound sonication to produce
micro/nano-sized (0.2-10 microns) crystals in monoclinic form. Homogeneous binary
blends of drug-polymer mixtures at various drug concentrations were obtained via
a thorough mixing. The analysis conducted via the single X-ray crystallography
determined the detailed structure of the crystallised PMOL in its monoclinic
form. The solid state and the morphology analyses of the PMOL in the binary
blends evaluated via differential scanning calorimetry (DSC), modulated
temperature DSC (MTDSC), scanning electron microscopy (SEM) and hot stage
microscopy (HSM) revealed the crystalline existence of the drug within the
amorphous polymeric matrices. The application of temperature controlled X-ray
diffraction (VTXRPD) to study the polymorphism of PMOL showed that the most
stable form I (monoclinic) was altered to its less stable form II (orthorhombic)
at high temperature (>112 degrees C) in the binary blends regardless of the drug
amount. Thus, VTXRD was used as a useful tool to monitor polymorphic
transformations of crystalline drug (e.g. PMOL) to assess their thermal stability
in terms of pharmaceutical product development and research.
PMID- 27511112
TI - Formulation and In Vitro Characterization of Thiolated Buccoadhesive Film of
Fluconazole.
AB - The present work is focused on the development of thiolated film for fluconazole
buccal delivery. To this end, unmodified polymers chitosan and sodium
carboxymethylcellulose (NaCMC) backbone was covalently modified by thioglycolic
acid (TGA) and cysteine, respectively. The thiolated buccoadhesive film was
evaluated in terms of thickness, weight uniformity, water-uptake capacity, drug
content, and release patterns. Moreover, mucoadhesion profile was investigated on
buccal mucosa. The resulting chitosan-TGA and NaCMC-cysteine conjugates displayed
171 +/- 13 and 380 +/- 19 MUmol thiol groups per gram of polymer (mean +/- SD; n
= 3), respectively. The water binding capacity of the thiolated film was
significantly ~2-fold higher (p < 0.05) as compared to unmodified film. The
obtained thiolated film displayed 5.8-fold higher mucoadhesive properties
compared with corresponding film. Controlled release of drugs from film was
observed over 8 h. The transport of fluconazole across excised buccal mucosa was
enhanced up to 17-fold in comparison with fluconazole applied in buffer. Based on
these findings, thiolated film seems to be promising for fluconazole buccal
delivery.
PMID- 27511113
TI - Nanocomposites of 2D-MoS2 nanosheets with the metal-organic framework, ZIF-8.
AB - The nanocomposites of MoS2 nanosheets with the metal-organic framework, ZIF-8,
have been synthesized starting with the layers of 1T-MoS2 generated by Li
intercalation of bulk MoS2, followed by exfoliation. The nanocomposites contain
the Zn-S bond and exhibit reasonably high surface areas. They exhibit CO2 uptake
higher than ZIF-8. Heating the nanocomposites to 900 degrees C under a N2
atmosphere yields MoS2-ZnS nanocomposites which show good activity for the
visible-light induced hydrogen evolution reaction.
PMID- 27511114
TI - TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic
fatty liver disease-related hepatocellular carcinoma.
AB - The number of patients with nonalcoholic fatty liver disease (NAFLD)-related
hepatocellular carcinoma (HCC) is increasing. To understand the molecular
features of the tumor phenotype, we aimed to clarify the overall landscape of
genetic aberrations accumulated in NAFLD-related HCC. Of 247 HCC patients who
underwent hepatectomy during 2010 to 2014 at a single center in Japan, 10 were
diagnosed with NAFLD-HCC based on strict clinical and pathologic criteria. We
analyzed the genetic aberrations of 11 NAFLD-HCC tumor samples from these 10
patients by whole-exome sequencing, targeted sequencing of the selected genes,
and copy number variation studies. Whole-exome sequencing revealed a mean somatic
mutation rate of 1.86 per megabase, and 12 genes were recurrently mutated in
NAFLD-HCCs. Targeted sequencing of the 26 selected genes (12 recurrently mutated
genes in whole-exome sequencing and 14 representative HCC-associated genes)
revealed that TERT promoter mutations occurred in 9 of 11 HCCs (82%), followed by
CTNNB1 (45%) and TP53 (36%) mutations. Array-based copy number variation studies
identified recurrent gains at 1q and 8q, and recurrent losses at 1p, 4q, 6q, 8p,
13q, 16p, 17p, and 18q. Notably, chromosome 8p loss occurred in all of the NAFLD
HCC samples. The current study provided the characteristics of genetic
aberrations in NAFLD-HCC and suggested that TERT promoter mutations and
chromosome 8p loss mainly contribute to NAFLD-related liver carcinogenesis.
PMID- 27511115
TI - Does cryotherapy improve skin circulation compared with compression and elevation
in preventing venous leg ulcers?
AB - This trial compared skin blood flow, temperature and incidence of venous leg
ulcers in patients with chronic venous disease using compression wraps and
elevation pillows. Patients with CEAP C4 skin damage and C5 history of ulcers
were randomly assigned to a cryotherapy intervention (n = 138) or placebo cuff
control (n = 138) applied to the lower legs over 9 months. The time the ulcers
healed prior to enrollment in the study for the cryotherapy group ranged from 1
to 2218 days (n = 8, median = 32 days); for the control group, the range was 24
to 489 days (n = 6, median = 390 days). There were no statistically significant
blood flow changes measured in perfusion units with a laser Doppler flowmetre
within or between the groups; mean difference between the groups was 0.62, P =
0.619. No differences were noted in skin temperature measured with an infrared
thermometer within and between the groups; mean difference between the groups was
-0.17 degrees C, P = 0.540. Cryotherapy did not improve skin blood flow or
temperature and did not show efficacy in preventing ulcers. However, at least 30%
of intervention and 50% of control participants were anticipated to develop an
ulcer during the study; only ~7% occurred. These findings suggest that strict
adherence to standard of care decreases the incidence of leg ulcers and remains a
best practice for leg ulcer prevention.
PMID- 27511116
TI - Overall survival of cancer patients with serum lactate dehydrogenase greater than
1000 IU/L.
AB - High level of serum lactate dehydrogenase (LDH) is a well-known poor prognostic
factor in patients with malignancies. However, there was no data on overall
survival (OS) in cancer patients with serum LDH level > 1000 IU/L, and the
prognostic value of the changes in LDH over time for OS had not been reported.
Clinical data of 311 cancer patients with metastatic disease with serum LDH >1000
IU/L (four times upper limit of normal) admitted consecutively to a single center
were reviewed in this retrospective study. LDH level ranged from 1002 to 8235 U/L
with a mean of 1689 U/L. The median OS was 1.7 months (95 % CI: 1.4-2.0). About
half of patients (n = 163, 52 %) died within 2 months with the median OS of 0.5
months (95 % CI: 0.3-0.7). Only 173 patients were indicated for salvage
treatment. Fifty-one patients' serum LDH level decreased to normal at 2 months
following chemotherapy; OS was significantly longer in these patients (22.6
months, 95 % CI: 10.9-34.3, p < 0.001) compared to those with persistently
abnormal serum LDH at 2 months (4.0 months, 95 % CI: 3.4-4.6). The independent
factors that increased the death risk were ECOG performance status 3-4 (HR: 2.05,
95 % CI: 1.42-2.97, p < 0.001), supportive care only (HR: 2.91, 95 % CI: 2.06
4.10, p < 0.001), and persistently abnormal serum LDH at 2 months (HR: 2.72, 95 %
CI: 1.67-4.42, p < 0.001). In conclusion, serum LDH level > 1000 IU/L predicted a
terminal stage in metastatic cancer patients. OS was significantly prolonged in
patients indicated for effective palliative treatment and LDH level decreased to
normal at 2 months.
PMID- 27511117
TI - Experimental verification of a predicted novel microRNA located in human PIK3CA
gene with a potential oncogenic function in colorectal cancer.
AB - PI3K/AKT signaling is involved in cell survival, proliferation, and migration. In
this pathway, PI3Kalpha enzyme is composed of a regulatory protein encoded by p85
gene and a catalytic protein encoded by PIK3CA gene. Human PIK3CA locus is
amplified in several cancers including lung and colorectal cancer (CRC).
Therefore, microRNAs (miRNAs) that are encoded within the PIK3CA gene might have
a role in cancer development. Here, we report a novel microRNA named PIK3CA-miR1
(EBI accession no. LN626315), which is located within PIK3CA gene. A DNA segment
corresponding to PIK3CA-premir1 sequence was transfected in human cell lines that
resulted in generation of mature exogenous PIK3CA-miR1. Following the
overexpression of PIK3CA-miR1, its predicted target genes (APPL1 and TrkC) were
significantly downregulated in the CRC-originated HCT116 and SW480 cell lines,
detected by qRT-PCR. Then, dual luciferase assay supported the interaction of
PIK3CA-miR1 with APPL1 and TrkC transcripts. Endogenous PIK3CA-miR1 expression
was also detected in several cell lines (highly in HCT116 and SW480) and highly
in CRC specimens. Consistently, overexpression of PIK3CA-premir1 in HCT116 and
SW480 cells resulted in significant reduction of the sub-G1 cell distribution and
apoptotic cell rate, as detected by flowcytometry, and resulted in increased cell
proliferation, as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide (MTT) assay. PIK3CA-miR1 overexpression also resulted
in Wnt signaling upregulation detected by Top/Fop assay. Overall, accumulative
evidences indicated the presence of a bona fide novel onco-miRNA encoded within
the PIK3CA oncogene, which is highly expressed in colorectal cancer and has a
survival effect in CRC-originated cells.
PMID- 27511118
TI - Molecular genetic analysis and phenotypic characteristics of a consanguineous
family with glycogen storage disease type Ia.
AB - Glycogen storage disease type-Ia (GSD-Ia) is a rare autosomal recessive disease
caused by a mutation in the gene encoding glucose-6-phosphate-alpha (G6PC). The
present study reported the case of a 3-month-old female Chinese patient with GSD
Ia born to consanguineous parents. The aim of the present study was to identify
the precise mutation of the G6PC gene associated with this family and to describe
the phenotypic characteristics of the patient. A comprehensive examination was
performed on the patient, including physical examination, vein blood gas
analysis, abdominal sonography and biochemical analyses. In addition, gene
sequencing was performed on the coding region of the G6PC gene to identify the
mutation. The patient was diagnosed with GSD-Ia and a G6PC missense mutation of
c.518T>C (p.L173P) located in a highly conserved area was identified. The
mutation is in a non-helical region of the protein, which previous studies have
suggested should result in a lesser effect on G6PC enzymatic activity and milder
phenotypic characteristics compared with mutations located in helical regions.
However, the severity of the disease phenotype in the subject of the present
study was inconsistent with that predicted from her genotype. The patient
suffered from serious hypoglycemia, lactic acidosis, increased triglycerides,
hepatic dysfunction, clear hepatomegaly and nephromegaly. The incidence of the
p.L173P mutation may be relatively high in the Chinese population. Knowledge of
the various phenotypic presentations of the p.L173P mutation may beneficial for
future investigations.
PMID- 27511119
TI - Rise of the tendon research.
PMID- 27511120
TI - Safety and efficacy of coil embolization of the septal perforator for septal
ablation in patients with hypertrophic obstructive cardiomyopathy.
AB - OBJECTIVE: The objective of this study was to evaluate safety, efficacy, and
durability of coil embolization of the major septal perforator of the left
anterior descending coronary artery in patients with hypertrophic obstructive
cardiomyopathy (HOCM). BACKGROUND: The long-term effect of coil embolization
therapy in HOCM patients is not well defined. METHODS: We evaluated 24
symptomatic HOCM patients in a single center who underwent coil embolization of
the septal perforator artery(ies). RESULTS: Twenty-four patients on optimal
medical therapy presented with NYHA functional class III (75%) or IV (25%)
underwent the procedure. The procedure was successful in 22 patients, with
significant reduction in left ventricular outflow tract (LVOT) gradient. The
functional class significantly improved to class I (54.2%) or II (41.7%) (P < =
0.01). The LVOT gradient was significantly lower during follow up
echocardiography (21.3 +/- 19 vs. 81.3 +/- 41 mm Hg; P < = 0.01).
Interventricular septal thickness decreased over time (16.3 +/- 3 vs. 18.5 +/- 2
mm, P< = 0.01). The procedure was aborted in one of the patients after the third
coil prolapsed from the septal perforator in to the left anterior descending
artery. The coil was effectively snared out. Three patients required additional
coil placement in the second major septal perforator. New permanent pacemaker
placement was required in one patient. However, three patients underwent ICD
implantation at follow up due to ventricular arrhythmias. CONCLUSIONS: The
results of this study suggest that the use of coil embolization for septal
ablation is safe, effective, and durable in patients with symptomatic HOCM. (c)
2016 Wiley Periodicals, Inc.
PMID- 27511121
TI - SIBLING- AND FAMILY-LEVEL CLUSTERING OF UNDERWEIGHT CHILDREN IN NORTHERN INDIA.
AB - Child undernutrition remains a major child health and developmental issue in low-
and middle-income countries. The concentration (clustering) of underweight
children among siblings at the family level is known to exist in India. This
study examined the extent and covariates of clustering of underweight children at
the sibling and family level in Uttar Pradesh, the largest state of northern
India. Clustering of underweight (low weight-for-age) children was assessed using
data on 7533 under-five children from the National Family Health Survey (NFHS)
conducted in 2005-06, analysed using binary logistic and binomial regression
models. Related bio-demographic, socioeconomic and health care variables were
used as covariates in the models. The odds of being underweight for the index
child were about two times higher (OR=2.34, p<0.001) if any of the siblings
within the household was malnourished or underweight. A longer birth interval
increased the odds of a child being underweight. The odds of underweight were
significantly lower (OR=0.69, p<0.001) for children born to normal-weight mothers
compared with those born to underweight mothers. Similarly, the odds of
underweight were significantly lower (OR=0.49, p=0.01) for children born to
educated mothers (high school and above) compared with those born to illiterate
mothers. The results of the binomial regression model suggested that the
deviations between observed and expected number of children were positive (3.09,
3.78 and 2.71) for 1, 2 and 2+ underweight children within the households of
underweight women, indicating the concentration of underweight children among
underweight/malnourished mothers. Underweight children were found to be clustered
among underweight mothers with multiple underweight siblings. The findings
suggest that policy interventions need to focus on underweight mothers with
multiple underweight children.
PMID- 27511123
TI - Sex hormone effects on autonomic and endothelial function.
AB - A video slideshow Introduction to the Symposium by symposium organiser Nina S.
Stachenfeld can be found here.
PMID- 27511122
TI - Transposable elements and miRNA: Regulation of genomic stability and plasticity.
AB - Transposable elements, the class of mobile DNA sequences that change their copies
or positions within the genome have an ever increasing role in shaping the
genetic and evolutionary landscape. Approximately half of the mammalian genome is
composed of repetitive elements, including LINE-1 (L1) elements. Because of their
ability to "copy and paste" into other regions of the genome, their activation
represent an opportunity as well as a threat, as L1-induced mutations results in
genomic instability and plasticity. On one hand L1 retrotransposition and
integration fosters genomic diversity and on the other, de-repressed L1 functions
as a driver of diseases such as cancer. The regulation of L1 is an area of
intense research and novel epigenetic mechanisms have recently been discovered to
now include DNA methylation, histone modifications, and miR-induced L1 silencing.
During development, reprogramming and in transformed cells, specific classes of
repetitive elements are upregulated, presumably due to the loss of epigenetic
regulation in this process, increasing the risk of L1-induced mutations. Here we
discuss how miR regulation of L1 activation fits into the complex picture of L1
repression in somatic cells and touch on some of the possible implications.
PMID- 27511124
TI - Enzyme overexpression - an exercise toward understanding regulation of heparan
sulfate biosynthesis.
AB - Biosynthesis of heparan sulfate (HS) involves conversion of D-glucuronic acid
(GlcA) to L-iduronic acid (IdoA) units catalyzed by glucuronyl C5-epimerase
(Hsepi). IdoA units are the favored substrate for 2-O-sulfotransferase (2OST). We
used HEK293 cells as a model to investigate the effects of overexpression of
these enzymes on HS structure. Overexpression of Hsepi alone resulted in an
unexpected increase in HS chain length. A Hsepi point-mutant (Y168A), devoid of
catalytic activity, failed to affect chain length. Moreover, the effect of Hsepi
overexpression on HS chain length was abolished by simultaneous overexpression of
2OST. These findings raise novel aspects on regulation of HS biosynthesis. We
propose a hypothetical enzyme-binding protein (EBP) with distinct, specific and
partly overlapping binding sites, the interactions of which will determine levels
of enzymes available to the biosynthetic process.
PMID- 27511125
TI - Neuroprotective effects of sodium hydrosulfide against beta-amyloid-induced
neurotoxicity.
AB - Alzheimer's disease (AD) is known to be caused by the accumulation of amyloid
beta peptide (Abeta). The accumulation of Abeta has been shown to cause learning
and memory impairment in rats, and it has been shown that hydrogen sulfide
donors, such as sodium hydrosulfide (NaHS) can attenuate these effects. However,
the underlying mechanisms have not yet been fully eludicated. This study was
designed to investigate whether NaHS attenuates the inflammation and apoptosis
induced by Abeta. We demonstrated that NaHS attenuated Abeta25-35-induced
neuronal reduction and apoptosis, and inhibited the activation of pro-caspase-3.
It also decreased the protein expresion of phosphodiesterase 5 (PDE5) in the
hippocampus of the rats. In addition, NaHS upregulated the expression of
peroxisome proliferator-activated receptor (PPAR)-alpha and PPAR-gamma, but it
did not affect the expression of PPAR-beta. Moreover, the Abeta25-35-exposed rats
exhibited a decrease in IkappaB-alpha degradation and an increase in nuclear
factor-kappaB (NF-kappaB) p65 phosphorylation levels, whereas these effects were
attenuated by NaHS. Our data suggest that NaHS prevents Abeta-induced
neurotoxicity via the upregulation of PPAR-alpha and PPAR-gamma and the
inhibition of PDE5. Hence NaHS may prove to be beneficial in the treatment of AD.
PMID- 27511126
TI - Yemen's Unprecedented Humanitarian Crisis: Implications for International
Humanitarian Law, the Geneva Convention, and the Future of Global Health
Security.
AB - The current humanitarian crisis in Yemen is unprecedented in many ways. The
Yemeni War tragedy is symptomatic of gross failures to recognize, by combatants,
existing humanitarian law and the Geneva Convention that have become the new norm
in unconventional armed conflicts and are increasingly replicated in Africa,
Afghanistan, and other areas of the Middle East with dire consequences on aid
workers and the noncombatant population. The health and humanitarian professions
must take collective responsibility in calling for all belligerent parties to
cease the massacre and commit to guaranteed medical assistance, humanitarian aid,
and the free flow of information and respect for the humanitarian principles that
protect the neutrality and impartiality of the humanitarian workforce. (Disaster
Med Public Health Preparedness. 2016;page 1 of 3).
PMID- 27511127
TI - Age, sex and arterial pressure: the kidney is essential.
PMID- 27511128
TI - The Leicester cerebral haemodynamics database: normative values and the influence
of age and sex.
AB - Normative values of physiological parameters hold significance in modern day
clinical decision-making. Lack of such normative values has been a major hurdle
in the translation of research into clinical practice. A large database
containing uniform recordings was constructed to allow more robust estimates of
normative ranges and also assess the influence of age and sex. Doppler recordings
were performed on healthy volunteers in the same laboratory, using similar
protocols and equipment. Beat-to-beat blood pressure, heart-rate,
electrocardiogram, and end-tidal CO2 were measured continuously. Bilateral
insonation of the middle cerebral arteries (MCAs) was performed using TCD
following a 15 min stabilisation, and a 5 min baseline recording. Good quality
Doppler recordings for both MCAs were obtained in 129 participants (57 female)
with a median age of 57 years (range 20-82). Age was found to influence baseline
haemodynamic and transfer function analysis parameters. Cerebral blood flow
velocity and critical closing pressure were the only sex-related differences
found, which was significantly higher in females than males. Normative values for
cerebral haemodynamic parameters have been defined in a large, healthy
population. Such age/sex-defined normal values can be used to reduce the burden
of collecting additional control data in future studies, as well as to identify
disease-associated changes.
PMID- 27511129
TI - Successful treatment of angiokeratoma circumscriptum naeviforme with long pulse
alexandrite laser.
PMID- 27511130
TI - Microscopic Charge Transport and Recombination Processes behind the Photoelectric
Hysteresis in Perovskite Solar Cells.
AB - The microscopic charge transport and recombination processes behind the widely
concerned photoelectric hysteresis in the perovskite solar cell have been
investigated with both in situ transient photovoltage/photocurrent measurements
and the semiconductor device simulation. Time-dependent behaviors of intensity
and direction of the photocurrent and photovoltage are observed under the steady
state bias voltages and open-circuit conditions. These charge processes reveal
the electric properties of the cell, demonstrating evolutions of both strength
and direction of the internal electric field during the hysteresis. Further
calculation indicates that this behavior is mainly attributed to both the
interfacial doping and defect effects induced by the ion accumulation, which may
be the origins for the general hysteresis in this cell.
PMID- 27511132
TI - Bis(4-nitraminofurazanyl-3-azoxy)azofurazan and Derivatives: 1,2,5-Oxadiazole
Structures and High-Performance Energetic Materials.
AB - Bis(4-nitraminofurazanyl-3-azoxy)azofurazan (1) and ten of its energetic salts
were prepared and fully characterized. Computational analysis based on
isochemical shielding surface and trigger bond dissociation enthalpy provide a
better understanding of the thermal stabilities for nitramine-furazans. These
energetic compounds exhibit good densities, high heats of formation, and
excellent detonation velocity and pressure. Some representative compounds, for
example, 1 (vD : 9541 m s(-1) ; P: 40.5 GPa), and 4 (vD : 9256 m s(-1) ; P: 38.0
GPa) exhibit excellent detonation performances, which are comparable with current
high explosives such as RDX (vD : 8724 m s(-1) ; P: 35.2 GPa) and HMX (vD : 9059
m s(-1) ; P: 39.2 GPa).
PMID- 27511131
TI - Insulin-like growth factor 1 rescues R28 retinal neurons from apoptotic death
through ERK-mediated BimEL phosphorylation independent of Akt.
AB - Insulin-like growth factor 1 (IGF-1) can provide long-term neurotrophic support
by activation of Akt, inhibition of FoxO nuclear localization and suppression of
Bim gene transcription in multiple neuronal systems. However, MEK/ERK activation
can also promote neuron survival through phosphorylation of BimEL. We explored
the contribution of the PI3K/Akt/FoxO and MEK/ERK/BimEL pathways in IGF-1
stimulated survival after serum deprivation (SD) of R28 cells differentiated to
model retinal neurons. IGF-1 caused rapid activation of Akt leading to FoxO1/3
T32/T24 phosphorylation, and prevented FoxO1/3 nuclear translocation and Bim mRNA
upregulation in response to SD. IGF-1 also caused MAPK/MEK pathway activation as
indicated by ERK1/2-T202/Y204 and Bim-S65 phosphorylation. Overexpression of
FoxO1 increased Bim mRNA expression and amplified the apoptotic response to SD
without shifting the serum response curve. Inhibition of Akt activation with
LY294002 or by Rictor knockdown did not block the protective effect of IGF-1,
while inhibition of MEK activity with PD98059 prevented Bim phosphorylation and
blocked IGF-1 protection. In addition, knockdown of Bim expression was protective
during SD, while co-silencing of FoxO1 and Fox03 expression had little effect.
Thus, the PI3K/Akt/FoxO pathway was not essential for protection from SD-induced
apoptosis by IGF-1 in R28 cells. Instead, IGF-1 protection was dependent on
activation of the MEK/ERK pathway leading to BimEL phosphorylation, which is
known to prevent Bax/Bak oligomerization and activation of the intrinsic
mitochondrial apoptosis pathway. These studies demonstrate the requirement of the
MEK/ERK pathway in a model of retinal neuron cell survival and highlight the cell
specificity for IGF-1 signaling in this response.
PMID- 27511133
TI - Selective recognition and stabilization of new ligands targeting the potassium
form of the human telomeric G-quadruplex DNA.
AB - The development of a ligand that is capable of distinguishing among the wide
variety of G-quadruplex structures and targeting telomeres to treat cancer is
particularly challenging. In this study, the ability of two anthraquinone
telomerase inhibitors (NSC749235 and NSC764638) to target telomeric G-quadruplex
DNA was probed. We found that these ligands specifically target the potassium
form of telomeric G-quadruplex DNA over the DNA counterpart. The characteristic
interaction with the telomeric G-quadruplex DNA and the anticancer activities of
these ligands were also explored. The results of this present work emphasize our
understanding of the binding selectivity of anthraquinone derivatives to G
quadruplex DNA and assists in future drug development for G-quadruplex-specific
ligands.
PMID- 27511134
TI - Editorial: non-invasive assessment of hepatic fibrosis in alpha-1 antitrypsin
deficiency using magnetic resonance elastography.
PMID- 27511135
TI - Editorial: non-invasive assessment of hepatic fibrosis in alpha-1 antitrypsin
deficiency using magnetic resonance elastography - authors' reply.
PMID- 27511136
TI - Letter: investigating the intestinal mucosa-associated microbiota - relevance and
potential pitfalls.
PMID- 27511137
TI - Letter: investigating the intestinal mucosa-associated microbiota - relevance and
potential pitfalls. Authors' reply.
PMID- 27511138
TI - Letter: cure of chronic hepatitis B and D after 12 years of treatment with low
dose standard interferon alfa-2b.
PMID- 27511139
TI - Letter: hepatitis B surface seroclearance does reduce the risk of hepatocellular
carcinoma - authors' reply.
PMID- 27511140
TI - Shaping of Metal-Organic Frameworks: From Fluid to Shaped Bodies and Robust
Foams.
AB - The applications of metal-organic frameworks (MOFs) toward industrial separation,
catalysis, sensing, and some sophisticated devices are drastically affected by
their intrinsic fragility and poor processability. Unlike organic polymers, MOF
crystals are insoluble in any solvents and are usually not thermoplastic, which
means traditional solvent- or melting-based processing techniques are not
applicable for MOFs. Herein, a continuous phase transformation processing
strategy is proposed for fabricating and shaping MOFs into processable fluids,
shaped bodies, and even MOF foams that are capable of reversible transformation
among these states. Based on this strategy, a cup-shaped Cu-MOF composite and
hierarchically porous MOF foam were developed for highly efficient catalytic C-H
oxidation (conv. 76% and sele. 93% for cup-shaped Cu-MOF composite and conv. 92%
and sele. 97% for porous foam) with ease of recycling and dramatically improved
kinetics. Furthermore, various MOF-based foams with low densities (<0.1 g cm(-3))
and high MOF loadings (up to 80 wt %) were obtained via this protocol. Imparted
with hierarchically porous structures and fully accessible MOFs uniformly
distributed, these foams presented low energy penalty (pressure drop <20 Pa, at
500 mL min(-1)) and showed potential applications as efficient membrane reactors.
PMID- 27511141
TI - Modifying the 5'-Cap for Click Reactions of Eukaryotic mRNA and To Tune
Translation Efficiency in Living Cells.
AB - The 5'-cap is a hallmark of eukaryotic mRNAs and plays fundamental roles in RNA
metabolism, ranging from quality control to export and translation. Modifying the
5'-cap may thus enable modulation of the underlying processes and investigation
or tuning of several biological functions. A straightforward approach is
presented for the efficient production of a range of N7-modified caps based on
the highly promiscuous methyltransferase Ecm1. We show that these, as well as
N(2) -modified 5'-caps, can be used to tune translation of the respective mRNAs
both in vitro and in cells. Appropriate modifications allow subsequent
bioorthogonal chemistry, as demonstrated by intracellular live-cell labeling of a
target mRNA. The efficient and versatile N7 manipulation of the mRNA cap makes
mRNAs amenable to both modulation of their biological function and intracellular
labeling, and represents a valuable addition to the chemical biology toolbox.
PMID- 27511143
TI - Tribotronic control of friction in oil-based lubricants with ionic liquid
additives.
AB - Atomic force microscopy (AFM) reveals that tribotronic control of friction using
an external potential applied to a gold surface is possible for ionic liquid (IL)
concentrations as low as 5 mol% in hexadecane. The IL used is
trihexyl(tetradecyl)phosphonium bis(2,4,4-trimethylpentyl)phosphinate, in which
both the cation and anion have surfactant-like structures, and is miscible with
hexadecane in all proportions. For IL concentrations less than 5 mol% friction
does not vary with applied potential, but for 5 mol% and above changing the
potential changes the composition of the IL boundary layer from cation-enriched
(negative potentials) to anion-enriched (positive potentials). As the lubricities
of the cation-rich and anion-rich boundary layers differ, this enables active
control of friction in oil-based lubricants.
PMID- 27511142
TI - Hyperphosphorylation amplifies UPF1 activity to resolve stalls in nonsense
mediated mRNA decay.
AB - Many gene expression factors contain repetitive phosphorylation sites for single
kinases, but the functional significance is poorly understood. Here we present
evidence for hyperphosphorylation as a mechanism allowing UPF1, the central
factor in nonsense-mediated decay (NMD), to increasingly attract downstream
machinery with time of residence on target mRNAs. Indeed, slowing NMD by
inhibiting late-acting factors triggers UPF1 hyperphosphorylation, which in turn
enhances affinity for factors linking UPF1 to decay machinery. Mutational
analyses reveal multiple phosphorylation sites contributing to different extents
to UPF1 activity with no single site being essential. Moreover, the ability of
UPF1 to undergo hyperphosphorylation becomes increasingly important for NMD when
downstream factors are depleted. This hyperphosphorylation-dependent feedback
mechanism may serve as a molecular clock ensuring timely degradation of target
mRNAs while preventing degradation of non-targets, which, given the prevalence of
repetitive phosphorylation among central gene regulatory factors, may represent
an important general principle in gene expression.
PMID- 27511144
TI - Shooting for the moon, and the stars?
PMID- 27511145
TI - The case for informative phase 2 trials in osteosarcoma.
PMID- 27511146
TI - When cancer gets gnarly.
PMID- 27511147
TI - The C Word.
PMID- 27511148
TI - Timing of androgen-deprivation therapy for prostate cancer: still a long way to
go - Authors' reply.
PMID- 27511149
TI - Timing of androgen-deprivation therapy for prostate cancer: still a long way to
go.
PMID- 27511150
TI - Salvage radiotherapy for patients with rising PSA.
PMID- 27511151
TI - Quality of life after video-assisted surgery for lung cancer.
PMID- 27511152
TI - Salvage radiotherapy for patients with rising PSA - Authors' reply.
PMID- 27511153
TI - Quality of life after video-assisted surgery for lung cancer.
PMID- 27511154
TI - Quality of life after video-assisted surgery for lung cancer.
PMID- 27511155
TI - Quality of life after video-assisted surgery for lung cancer.
PMID- 27511156
TI - Quality of life after video-assisted surgery for lung cancer - Author's reply.
PMID- 27511157
TI - Venetoclax in cancer therapy and potential effects on bone.
PMID- 27511158
TI - International Myeloma Working Group consensus criteria for response and minimal
residual disease assessment in multiple myeloma.
AB - Treatment of multiple myeloma has substantially changed over the past decade with
the introduction of several classes of new effective drugs that have greatly
improved the rates and depth of response. Response criteria in multiple myeloma
were developed to use serum and urine assessment of monoclonal proteins and bone
marrow assessment (which is relatively insensitive). Given the high rates of
complete response seen in patients with multiple myeloma with new treatment
approaches, new response categories need to be defined that can identify
responses that are deeper than those conventionally defined as complete response.
Recent attempts have focused on the identification of residual tumour cells in
the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive
imaging techniques can be used to detect the presence of residual disease outside
of the bone marrow. Combining these new methods, the International Myeloma
Working Group has defined new response categories of minimal residual disease
negativity, with or without imaging-based absence of extramedullary disease, to
allow uniform reporting within and outside clinical trials. In this Review, we
clarify several aspects of disease response assessment, along with endpoints for
clinical trials, and highlight future directions for disease response
assessments.
PMID- 27511159
TI - Novel therapeutic targets on the horizon for lung cancer.
AB - Lung cancer is a leading cause of cancer-related mortality worldwide, and is
classically divided into two major histological subtypes: non-small-cell lung
cancer (NSCLC) and small-cell lung cancer (SCLC). Although NSCLC and SCLC are
considered distinct entities with different genomic landscapes, emerging evidence
highlights a convergence in therapeutically relevant targets for both
histologies. In adenocarcinomas with defined alterations such as EGFR mutations
and ALK translocations, targeted therapies are now first-line standard of care.
By contrast, many experimental and targeted agents remain largely unsuccessful
for SCLC. Intense preclinical research and clinical trials are underway to
exploit unique traits of lung cancer, such as oncogene dependency, DNA damage
response, angiogenesis, and cellular plasticity arising from presence of cancer
stem cell lineages. In addition, the promising clinical activity observed in
NSCLC in response to immune checkpoint blockade has spurred great interest in the
field of immunooncology, with the scope to develop a diverse repertoire of
synergistic and personalised immunotherapeutics. In this Review, we discuss novel
therapeutic agents for lung cancer that are in early-stage development, and how
prospective clinical trials and drug development may be shaped by a deeper
understanding of this heterogeneous disease.
PMID- 27511160
TI - Brazilian health-care policy for targeted oncology therapies and companion
diagnostic testing.
AB - A growing understanding of the molecular pathology of tumours combined with a
surge of new drugs and associated diagnostic technologies (ie, precision
medicine) has translated into substantial improvements in survival for patients
with cancer. However, to achieve the promise that precision medicine has to offer
will require overcoming hurdles within a national health-care system in which it
is to be implemented. Brazil is one such nation, an emerging middle-income
country with a very complex health-care system. To address the challenges
associated with implementing precision medicine into a country such as Brazil, a
group of experts convened (Nov 16-18, 2015, Miami) to discuss challenges related
to precision medicine within an oncology setting. Complex regulatory hurdles, a
shortage of human and technical resources, and the complexities of a two-tiered
health-care delivery system were all identified as the main shortcomings to
effectively implementing this new field of medicine. A path forward was proposed
that relies on active collaboration between clinicians, private organisations,
and government. It seems entirely possible that, despite many intrinsic economic
and political problems, Brazil can readily emerge as a model for other countries
in Latin America for the potential benefits of precision medicine and companion
diagnostics.
PMID- 27511161
TI - Hirschsprung disease as a yet undescribed phenotype in a patient with ARID1B
mutation.
AB - Mutations in the BAF complex (mammalian SWI/SNF complex) are responsible for
Coffin-Siris syndrome, which is characterized by developmental delay, distinctive
facial features, hirsutism, and hypoplasia/aplasia of the fifth
finger/fingernails. Hirschsprung disease is characterized by defective stem cells
in the enteric neural system, and the involvement of multiple signaling cascades
has been implicated. So far, the roles of the BAF complex in the genesis of
Hirschsprung disease have remained unknown. Here, we document a patient with
coarse facial features, postnatal growth failure, developmental delay, epilepsy,
and hypoplasia of the corpus callosum and cerebellum but without a hypoplastic
fifth finger/fingernail. In addition, he had Hirschsprung disease. Exome
sequencing with a gene set representing a total of 4,813 genes with known
relationships to human diseases revealed a heterozygous frameshift mutation in
ARID1B (c.5789delC p.Pro1930Leufs*44). The presence of a congenital cataract and
Hirschsprung disease in the presently reported patient further expands the
phenotypic spectrum of patients with ARID1B mutations and may suggest the
potential role of the BAF complex in the pathogenesis of the enteric neural
system. The present observation is in agreement with a recent study of Drosophila
neuroblasts showing that the dysregulated BAF complex leads to an abnormal
lineage progression of neural stem cell lineages and that Hirschsprung disease is
caused by abnormal stem cell lineages in the peripheral neural tissues. (c) 2016
Wiley Periodicals, Inc.
PMID- 27511162
TI - C-Banding of Plant Chromosomes.
AB - C-banding is used to differentially stain metaphase chromosomes in organisms
having appreciable amounts of constitutive heterochromatin. Its primary benefits
are that it is an inexpensive and a relatively fast method of identifying
individual chromosomes and morphological or karyotypic variation, including large
chromosomal rearrangements and aneuploidies. We currently employ this technique
with considerable effect in genome analysis of oat (Avena sativa) and related
grass species, though it has been most extensively used for chromosome analysis
of wheat (Triticum aestivum) and its relatives of the Triticeae.
PMID- 27511163
TI - Chromosome Painting by GISH and Multicolor FISH.
AB - Fluorescent in situ hybridization (FISH) is a powerful cytogenetic technique for
identifying chromosomes and mapping specific genes and DNA sequences on
individual chromosomes. Genomic in situ hybridization (GISH) and multicolor FISH
(mc-FISH) represent two special types of FISH techniques. Both GISH and mc-FISH
experiments have general steps and features of FISH, including chromosome
preparation, probe labeling, blocking DNA preparation, target-probe DNA
hybridization, post-hybridization washes, and hybridization signal detection.
Specifically, GISH uses total genomic DNA from two species as probe and blocking
DNA, respectively, and it can differentiate chromosomes from different genomes.
The mc-FISH takes advantage of simultaneous hybridization of several DNA probes
labeled by different fluorochromes to different targets on the same chromosome
sample. Hybridization signals from different probes are detected using different
fluorescence filter sets. Multicolor FISH can provide more structural details for
target chromosomes than single-color FISH. In this chapter, we present the
general experimental procedures for these two techniques with specific details in
the critical steps we have modified in our laboratories.
PMID- 27511164
TI - Fluorescent In Situ Hybridization on Extended Chromatin Fibers for High
Resolution Analysis of Plant Chromosomes.
AB - Fiber FISH is a high-resolution cytogenetic method and a powerful tool of genome
analysis to study the localization and the physical organization of markers,
genes, and repetitive sequences on a molecular level. Measurement of physical
distances between sequences can be performed along extended chromatin fibers with
the resolution of up to 1 kb and is applicable to all plant species.
PMID- 27511165
TI - Tyramide Signal Amplification: Fluorescence In Situ Hybridization for Identifying
Homoeologous Chromosomes.
AB - Tyramide signal amplification (TSA) fluorescence in situ hybridization (FISH) has
been shown as a valuable molecular tool for visualizing specific amplified DNA
sequences in chromosome preparations. This chapter describes how to perform TSA
FISH, paying special interest to its two critical steps: probe generation and
metaphase plate generation. The potential of physically mapping 12S-globulin
sequences by TSA-FISH as a means of identifying homeology among chromosome
regions of Avena species was tested and is discussed.
PMID- 27511166
TI - Localization of Low-Copy DNA Sequences on Mitotic Chromosomes by FISH.
AB - Fluorescence in situ hybridization (FISH) is a widely used method to localize DNA
sequences on mitotic and meiotic chromosomes and interphase nuclei. It was
developed in early 1980s and since then it has contributed to numerous studies
and important discoveries. Over the decades, the protocol was modified for ease
of use, allowing for localizing multiple probes simultaneously and increasing its
sensitivity and specificity. Despite the continuous improvements, the ability to
detect short single-copy sequences of only a few kilobases or less, such as
genes, remains limited. Here, we provide a detailed protocol for detection of
short, single- or low-copy sequences on plant mitotic metaphase chromosomes.
PMID- 27511167
TI - Immunolabeling and In Situ Labeling of Isolated Plant Interphase Nuclei.
AB - Specific labeling of proteins and nucleic acids by immunofluorescence or in situ
techniques is an important adjunct to microscopical analysis for cell biology.
Labeling of nuclear structures in intact complex tissues is often hampered by
problems of penetration of the macromolecular labeling reagents needed. Here we
describe a method of labeling isolated plant nuclei that we have found to be a
useful approach that can help to overcome these problems.
PMID- 27511168
TI - Manipulation of Homologous and Homoeologous Chromosome Recombination in Wheat.
AB - Given the sizes of the three genomes in wheat (A, B, and D) and a limited number
of chiasmata formed in meiosis, recombination by crossing-over is a very rare
event. It is also restricted to very similar homologues; the pairing homoeologous
(Ph) system of wheat prevents differentiated chromosomes from pairing and
crossing-over. This chapter presents an overview and describes several systems by
which the frequency or density of crossing-over can be increased, both in
homologues and homoeologues. It also presents the standard system of E.R. Sears
for engineering alien chromosome transfers into wheat.
PMID- 27511169
TI - Dissecting Plant Chromosomes by the Use of Ionizing Radiation.
AB - Radiation treatment of genomes is used to generate chromosome breaks for numerous
applications. This protocol describes the preparation of seeds and the
determination of the optimal level of irradiation dosage for the creation of a
radiation hybrid (RH) population. These RH lines can be used to generate high
resolution physical maps for the assembly of sequenced genomes as well as the
fine mapping of genes. This procedure can also be used for mutation breeding and
forward/reverse genetics.
PMID- 27511171
TI - Flow Sorting Plant Chromosomes.
AB - Nuclear genomes of many important plant species are tremendously complicated to
map and sequence. The ability to isolate single chromosomes, which represent
small units of nuclear genome, is priceless in many areas of plant research
including cytogenetics, genomics, and proteomics. Flow cytometry is the only
technique which can provide large quantities of pure chromosome fractions
suitable for downstream applications including physical mapping, preparation of
chromosome-specific BAC libraries, sequencing, and optical mapping. Here, we
describe step-by-step procedure of preparation of liquid suspensions of intact
mitotic metaphase chromosomes and their flow cytometric analysis and sorting.
PMID- 27511170
TI - Optical Nano-mapping and Analysis of Plant Genomes.
AB - Application of optical mapping based on BioNano Genomics Irys((r)) technology (
http://www.bionanogenomics.com/ ) is growing rapidly since its debut in November
2012. The technology can be used to facilitate genome sequence assembly and
analysis of genome structural variations. We describe here the detailed protocol
that we used to generate a whole genome BioNano map for Aegilops tauschii, the D
genome progenitor of hexaploid wheat (Triticum aestivum). We are using the whole
genome BioNano map to validate sequence assembly based on the next-generation
sequencing, order sequence scaffolds, and ultimately build pseudomolecules for
the genome.
PMID- 27511172
TI - Construction of BAC Libraries from Flow-Sorted Chromosomes.
AB - Cloned DNA libraries in bacterial artificial chromosome (BAC) are the most widely
used form of large-insert DNA libraries. BAC libraries are typically represented
by ordered clones derived from genomic DNA of a particular organism. In the case
of large eukaryotic genomes, whole-genome libraries consist of a hundred thousand
to a million clones, which make their handling and screening a daunting task. The
labor and cost of working with whole-genome libraries can be greatly reduced by
constructing a library derived from a smaller part of the genome. Here we
describe construction of BAC libraries from mitotic chromosomes purified by flow
cytometric sorting. Chromosome-specific BAC libraries facilitate positional gene
cloning, physical mapping, and sequencing in complex plant genomes.
PMID- 27511173
TI - The Chromosome Microdissection and Microcloning Technique.
AB - Chromosome microdissection followed by microcloning is an efficient tool
combining cytogenetics and molecular genetics that can be used for the
construction of the high density molecular marker linkage map and fine physical
map, the generation of probes for chromosome painting, and the localization and
cloning of important genes. Here, we describe a modified technique to
microdissect a single chromosome, paint individual chromosomes, and construct
single-chromosome DNA libraries.
PMID- 27511174
TI - Immunolocalization on Whole Anther Chromosome Spreads for Male Meiosis.
AB - Immunolocalization of cells undergoing meiosis has proven to be one of the most
important tools to decipher chromatin-associated protein dynamics and causal
relationships. Here, we describe a protocol established for maize which is easily
adaptable to other plants, for example, with minor modifications to Arabidopsis
as stated here. In contrast to many other protocols, the following protocol is
based on fixation by a 3:1 mixture of ethanol and acetic acid. Spreading of cells
is followed by freeze-shattering, protein antigenicity retrieval by a hot citrate
buffer bath, antibody incubations and washes, and DNA staining.
PMID- 27511175
TI - Mapping Recombination Initiation Sites Using Chromatin Immunoprecipitation.
AB - Genome-wide maps of recombination sites provide valuable information not only on
the recombination pathway itself but also facilitate the understanding of genome
dynamics and evolution. Here, we describe a chromatin immunoprecipitation (ChIP)
protocol to map the sites of recombination initiation in plants with maize used
as an example. ChIP is a method that allows identification of chromosomal sites
occupied by specific proteins. Our protocol utilizes RAD51, a protein involved in
repair of double-strand breaks (DSBs) that initiate meiotic recombination, to
identify DSB formation hotspots. Chromatin is extracted from meiotic flowers,
sheared and enriched in fragments bound to RAD51. Genomic location of the protein
is then identified by next-generation sequencing. This protocol can also be used
in other species of plants, animals, and fungi.
PMID- 27511176
TI - Chromatin Immunoprecipitation to Study The Plant Epigenome.
AB - Chromatin immunoprecipitation (ChIP) has been widely used for studying in vivo
protein-DNA interactions for decades. ChIP is a powerful tool that is adaptable
for studying epigenetic modifications at certain genomic loci or the genomic
level. Given its utility in studying the epigenome and the many technical
challenges, we present a detailed in-lab ChIP protocol primarily used for
studying histone modifications in plants, but can be easily adapted for other
chromatin targets in other species.
PMID- 27511177
TI - Erratum to: development and psychometric testing of a new instrument to measure
factors influencing women's breast cancer prevention behaviors (ASSISTS).
PMID- 27511178
TI - Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin
Color Differentiation in Red Tilapia.
AB - Red tilapia is becoming more popular for aquaculture production in China in
recent years. However, the pigmentation differentiation in genetic breeding is
the main problem limiting its development of commercial red tilapia culture and
the genetic basis of skin color variation is still unknown. In this study, we
conducted Illumina sequencing of transcriptome on three color variety red
tilapia. A total of 224,895,758 reads were generated, resulting in 160,762
assembled contigs that were used as reference contigs. The contigs of red tilapia
transcriptome had hits in the range of 53.4% to 86.7% of the unique proteins of
zebrafish, fugu, medaka, three-spined stickleback and tilapia. And 44,723 contigs
containing 77,423 simple sequence repeats (SSRs) were identified, with 16,646
contigs containing more than one SSR. Three skin transcriptomes were compared
pairwise and the results revealed that there were 148 common significantly
differentially expressed unigenes and several key genes related to pigment
synthesis, i.e. tyr, tyrp1, silv, sox10, slc24a5, cbs and slc7a11, were included.
The results will facilitate understanding the molecular mechanisms of skin
pigmentation differentiation in red tilapia and accelerate the molecular
selection of the specific strain with consistent skin colors.
PMID- 27511179
TI - Cardiac involvement in hereditary myopathy with early respiratory failure: A
cohort study.
AB - OBJECTIVE: To assess whether hereditary myopathy with early respiratory failure
(HMERF) due to the c.951434T>C; (p.Cys31712Arg) TTN missense mutation also
includes a cardiac phenotype. METHOD: Clinical cohort study of our HMERF cohort
using ECG, 2D echocardiogram, and cross-sectional cardiac imaging with MRI or CT.
RESULTS: We studied 22 participants with the c.951434T>C; (p.Cys31712Arg) TTN
missense mutation. Three were deceased. Cardiac conduction abnormalities were
identified in 7/22 (32%): sustained atrioventricular tachycardia (n = 2), atrial
fibrillation (n = 2), nonsustained atrial tachycardia (n = 1), premature
supraventricular complexes (n = 1), and unexplained sinus bradycardia (n = 1). In
addition, 4/22 (18%) had imaging evidence of otherwise unexplained
cardiomyopathy. These findings are supported by histopathologic correlation
suggestive of myocardial cytoskeletal remodeling. CONCLUSIONS: Coexisting cardiac
and skeletal muscle involvement is not uncommon in patients with HMERF arising
due to the c.951434T>C; (p.Cys31712Arg) TTN mutation. All patients with
pathogenic or putative pathogenic TTN mutations should be offered periodic
cardiac surveillance.
PMID- 27511180
TI - Twelve-month recovery of medical decision-making capacity following traumatic
brain injury.
AB - OBJECTIVE: To investigate recovery of medical decision-making capacity (MDC) over
the first year following traumatic brain injury (TBI). METHODS: A total of 177
participants (111 persons with TBI and 66 healthy controls) were recruited from
an inpatient/outpatient TBI rehabilitation unit and outpatient neurology
department. Participants with TBI were classified by injury severity into
subgroups: mild TBI (mTBI; n = 28), complicated mild TBI (cmTBI; n = 23), and
moderate/severe TBI (msevTBI; n = 60). Control and TBI groups were compared at 1
month (t1), 6 months (t2), and 12 months (t3) postinjury using the Capacity to
Consent to Treatment Instrument (CCTI), which evaluates MDC using 5 consent
standards: expressing choice, reasonable choice, appreciation, reasoning, and
understanding. RESULTS: Relative to controls, no TBI group displayed impairment
on CCTI expressing choice or reasonable choice at any timepoint. Those with mTBI
had reduced appreciation and understanding at t1, which resolved by t2. The cmTBI
and msevTBI groups were impaired on all 3 complex consent standards at t1. While
patients with cmTBI improved to a level similar to controls by t3, those with
msevTBI remained impaired on reasoning and understanding. Across all TBI groups,
notable MDC improvement only occurred over the first 6 months postinjury.
CONCLUSIONS: Over 1 year, most individuals with mTBI or cmTBI regain MDC, while
many individuals with msevTBI have lingering deficits in reasoning and
comprehension of treatment information. Clinical recovery of MDC occurs primarily
during the first 6 months post-TBI regardless of injury severity. Clinicians can
therefore identify MDC outcomes in TBI at 6 months postinjury.
PMID- 27511181
TI - Sirolimus for epilepsy in children with tuberous sclerosis complex: A randomized
controlled trial.
AB - OBJECTIVE: To investigate whether mammalian target of rapamycin complex 1
(mTORC1) inhibitors could reduce seizure frequency in children with tuberous
sclerosis complex (TSC). METHODS: Due to slow inclusion rate, target inclusion of
30 children was not reached. Twenty-three children with TSC and intractable
epilepsy (age 1.8-10.9 years) were randomly assigned (1:1) to open-label, add-on
sirolimus treatment immediately or after 6 months. Sirolimus was titrated to
trough levels of 5-10 ng/mL. Primary endpoint was seizure frequency change during
the sixth month of sirolimus treatment. RESULTS: Intention-to-treat analysis
showed sirolimus treatment resulted in 41% seizure frequency decrease (95%
confidence interval [CI] -69% to +14%; p = 0.11) compared to the standard-care
period. Per protocol analysis of 14 children who reached sirolimus target trough
levels in the sixth sirolimus month showed a seizure frequency decrease of 61%
(95% CI -86% to +6%; p = 0.06). Cognitive development did not change. All
children had adverse events. Five children discontinued sirolimus prematurely.
CONCLUSIONS: We describe a randomized controlled trial for a non-antiepileptic
drug that directly targets a presumed causal mechanism of epileptogenesis in a
genetic disorder. Although seizure frequency decreased, especially in children
reaching target trough levels, we could not show a significant benefit. Larger
trials or meta-analyses are needed to investigate if patients with TSC with
seizures benefit from mTORC1 inhibition. This trial was registered at
trialregister.nl (NTR3178) and supported by the Dutch Epilepsy Foundation.
CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that sirolimus
does not significantly reduce seizure frequency in children with TSC and
intractable epilepsy. The study lacked the precision to exclude a benefit from
sirolimus.
PMID- 27511184
TI - mTORC1 inhibition for epilepsy in TSC: Feasibility in question.
PMID- 27511183
TI - Evolution of clinical features in possible DLB depending on FP-CIT SPECT result.
AB - OBJECTIVE: To test the hypothesis that core and suggestive features in possible
dementia with Lewy bodies (DLB) would vary in their ability to predict an
abnormal dopamine transporter scan and therefore a follow-up diagnosis of
probable DLB. A further objective was to assess the evolution of core and
suggestive features in patients with possible DLB over time depending on the
(123)I-FP-CIT SPECT scan result. METHODS: A total of 187 patients with possible
DLB (dementia plus one core or one suggestive feature) were randomized to have
dopamine transporter imaging or to follow-up without scan. DLB features were
compared at baseline and at 6-month follow-up according to imaging results and
follow-up diagnosis. RESULTS: For the whole cohort, the baseline frequency of
parkinsonism was 30%, fluctuations 29%, visual hallucinations 24%, and REM sleep
behavior disorder 17%. Clinician-rated presence of parkinsonism at baseline was
significantly (p = 0.001) more frequent and Unified Parkinson's Disease Rating
Scale (UPDRS) score at baseline was significantly higher (p = 0.02) in patients
with abnormal imaging. There was a significant increase in UPDRS score in the
abnormal scan group over time (p < 0.01). There was relatively little evolution
of the rest of the DLB features regardless of the imaging result. CONCLUSIONS: In
patients with possible DLB, apart from UPDRS score, there was no difference in
the evolution of DLB clinical features over 6 months between cases with normal
and abnormal imaging. Only parkinsonism and dopamine transporter imaging helped
to differentiate DLB from non-DLB dementia.
PMID- 27511185
TI - Does early (treatment in) BENEFIT lead to late MS benefit?
PMID- 27511186
TI - Retinal microvasculature and white matter microstructure: The Rotterdam Study.
AB - OBJECTIVE: To investigate whether retinal microvascular damage is related to
normal-appearing white matter microstructure on diffusion tensor MRI. METHODS: We
included 2,436 participants (age >=45 years) from the population-based Rotterdam
Study (2005-2009) who had gradable retinal images and brain MRI scans. Retinal
arteriolar and venular calibers were measured semiautomatically on fundus
photographs. White matter microstructure was assessed using diffusion tensor MRI.
We used linear regression models to investigate the associations of retinal
vascular calibers with markers of normal-appearing white matter microstructure,
adjusting for age, sex, the fellow vascular caliber, and additionally for
structural MRI markers and cardiovascular risk factors. RESULTS: Narrower
arterioles and wider venules were associated with poor white matter
microstructure: adjusted difference in fractional anisotropy per SD decrease in
arteriolar caliber -0.061 (95% confidence interval -0.106 to -0.016), increase in
venular caliber -0.054 (-0.096 to -0.011), adjusted difference in mean
diffusivity per SD decrease in arteriolar caliber 0.048 (0.007-0.088), and
increase in venular caliber 0.047 (0.008-0.085). The associations for venules
were more prominent in women. CONCLUSIONS: Retinal vascular calibers are related
to normal-appearing white matter microstructure. This suggests that microvascular
damage in the white matter is more widespread than visually detectable as white
matter lesions.
PMID- 27511182
TI - The 11-year long-term follow-up study from the randomized BENEFIT CIS trial.
AB - OBJECTIVE: To assess outcomes for patients treated with interferon beta-1b
immediately after clinically isolated syndrome (CIS) or after a short delay.
METHODS: Participants in BENEFIT (Betaferon/Betaseron in Newly Emerging MS for
Initial Treatment) were randomly assigned to receive interferon beta-1b (early
treatment) or placebo (delayed treatment). After conversion to clinically
definite multiple sclerosis (CDMS) or 2 years, patients on placebo could switch
to interferon beta-1b or another treatment. Eleven years after randomization,
patients were reassessed. RESULTS: Two hundred seventy-eight (59.4%) of the
original 468 patients (71.3% of those eligible at participating sites) were
enrolled (early: 167 [57.2%]; delayed: 111 [63.1%]). After 11 years, risk of CDMS
remained lower in the early-treatment arm compared with the delayed-treatment arm
(p = 0.0012), with longer time to first relapse (median [Q1, Q3] days: 1,888
[540, not reached] vs 931 [253, 3,296]; p = 0.0005) and lower overall annualized
relapse rate (0.21 vs 0.26; p = 0.0018). Only 25 patients (5.9%, overall; early,
4.5%; delayed, 8.3%) converted to secondary progressive multiple sclerosis.
Expanded Disability Status Scale scores remained low and stable, with no
difference between treatment arms (median [Q1, Q3]: 2.0 [1.0, 3.0]). The early
treatment group had better Paced Auditory Serial Addition Task-3 total scores (p
= 0.0070). Employment rates remained high, and health resource utilization tended
to be low in both groups. MRI metrics did not differ between groups. CONCLUSIONS:
Although the delay in treatment was relatively short, several clinical outcomes
favored earlier treatment. Along with low rates of disability and disease
progression in both groups, this supports the value of treatment at CIS.
CLINICALTRIALSGOV IDENTIFIER: NCT01795872. CLASSIFICATION OF EVIDENCE: This study
provides Class IV evidence that early compared to delayed treatment prolongs time
to CDMS in CIS after 11 years.
PMID- 27511187
TI - How reliable is 18FDG PET for predicting the onset of Huntington's disease?
PMID- 27511189
TI - Paraneoplastic syndrome demonstrated on 99mTc-HMDP bone scan.
AB - A 23-year-old man, with no relevant medical history, presented with inflammatory
peripheral and axial polyarthritis, wrist pain, and persistent low-grade fever
for the past 4 months. A bone scintigraphy showed intense periosteal early and
delayed uptake in long bones, with normal uptake in the spine, pelvis, and rib
cage, and no clear focus of hypermetabolism. CT scan revealed a mediastinal mass.
A biopsy of the mass demonstrated Hodgkin lymphoma with bulky disease. This
paraneoplastic syndrome as the first sign of intrathoracic Hodgkin's disease is
rare.
PMID- 27511188
TI - The value of 18F-FDG PET before and after induction chemotherapy for the early
prediction of a poor pathologic response to subsequent preoperative
chemoradiotherapy in oesophageal adenocarcinoma.
AB - PURPOSE: The purpose of our study was to determine the value of 18F-FDG PET
before and after induction chemotherapy in patients with oesophageal
adenocarcinoma for the early prediction of a poor pathologic response to
subsequent preoperative chemoradiotherapy (CRT). METHODS: In 70 consecutive
patients receiving a three-step treatment strategy of induction chemotherapy and
preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18F-FDG PET scans
were performed before and after induction chemotherapy (before preoperative CRT).
SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG)
were determined at these two time points. The predictive potential of (the change
in) these parameters for a poor pathologic response, progression-free survival
(PFS) and overall survival (OS) was assessed. RESULTS: A poor pathologic response
after induction chemotherapy and preoperative CRT was found in 27 patients (39
%). Patients with a poor pathologic response experienced less of a reduction in
TLG after induction chemotherapy (p < 0.01). The change in TLG was predictive for
a poor pathologic response at a threshold of -26 % (sensitivity 67 %, specificity
84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of
0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a
significantly worse PFS (p = 0.02), but not OS (p = 0.18). CONCLUSIONS: 18F-FDG
PET appears useful to predict a poor pathologic response as well as PFS early
after induction chemotherapy in patients with oesophageal adenocarcinoma
undergoing a three-step treatment strategy. As such, the early 18F-FDG PET
response after induction chemotherapy could aid in individualizing treatment by
modification or withdrawal of subsequent preoperative CRT in poor responders.
PMID- 27511190
TI - Genomic Methods Take the Plunge: Recent Advances in High-Throughput Sequencing of
Marine Mammals.
AB - The dramatic increase in the application of genomic techniques to non-model
organisms (NMOs) over the past decade has yielded numerous valuable contributions
to evolutionary biology and ecology, many of which would not have been possible
with traditional genetic markers. We review this recent progression with a
particular focus on genomic studies of marine mammals, a group of taxa that
represent key macroevolutionary transitions from terrestrial to marine
environments and for which available genomic resources have recently undergone
notable rapid growth. Genomic studies of NMOs utilize an expanding range of
approaches, including whole genome sequencing, restriction site-associated DNA
sequencing, array-based sequencing of single nucleotide polymorphisms and target
sequence probes (e.g., exomes), and transcriptome sequencing. These approaches
generate different types and quantities of data, and many can be applied with
limited or no prior genomic resources, thus overcoming one traditional limitation
of research on NMOs. Within marine mammals, such studies have thus far yielded
significant contributions to the fields of phylogenomics and comparative
genomics, as well as enabled investigations of fitness, demography, and
population structure. Here we review the primary options for generating genomic
data, introduce several emerging techniques, and discuss the suitability of each
approach for different applications in the study of NMOs.
PMID- 27511191
TI - Nitrogen assimilation system in maize is regulated by developmental and tissue
specific mechanisms.
AB - KEY MESSAGE: We found metabolites, enzyme activities and enzyme transcript
abundances vary significantly across the maize lifecycle, but weak correlation
exists between the three groups. We identified putative genes regulating nitrate
assimilation. Progress in improving nitrogen (N) use efficiency (NUE) of crop
plants has been hampered by the complexity of the N uptake and utilisation
systems. To understand this complexity we measured the activities of seven
enzymes and ten metabolites related to N metabolism in the leaf and root tissues
of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 (-) throughout the
lifecycle. The amino acids had remarkably similar profiles across the lifecycle
except for transient responses, which only appeared in the leaves for aspartate
or in the roots for asparagine, serine and glycine. The activities of the enzymes
for N assimilation were also coordinated to a certain degree, most noticeably
with a peak in root activity late in the lifecycle, but with wide variation in
the activity levels over the course of development. We analysed the
transcriptional data for gene sets encoding the measured enzymes and found that,
unlike the enzyme activities, transcript levels of the corresponding genes did
not exhibit the same coordination across the lifecycle and were only weakly
correlated with the levels of various amino acids or individual enzyme
activities. We identified gene sets which were correlated with the enzyme
activity profiles, including seven genes located within previously known
quantitative trait loci for enzyme activities and hypothesise that these genes
are important for the regulation of enzyme activities. This work provides
insights into the complexity of the N assimilation system throughout development
and identifies candidate regulatory genes, which warrant further investigation in
efforts to improve NUE in crop plants.
PMID- 27511192
TI - De novo transcriptome analysis reveals insights into dynamic homeostasis
regulation of somatic embryogenesis in upland cotton (G. hirsutum L.).
AB - Plant regeneration via somatic embryogenesis (SE) is the key step for genetic
improvement of cotton (Gossypium hirsutum L.) through genetic engineering
mediated by Agrobacteria, but the molecular mechanisms underlying SE in cotton is
still unclear. Here, RNA-Sequencing was used to analyze the genes expressed
during SE and their expression dynamics using RNAs isolated from non-embryogenic
callus (NEC), embryogenic callus (EC) and somatic embryos (SEs). A total of 101,
670 unigenes were de novo assembled. The genes differentially expressed (DEGs)
amongst NEC, EC and SEs were identified, annotated and classified. More DEGs were
found between SEs and EC than between EC and NEC. A significant number of DEGs
were related to hormone homeostasis, stress and ROS responses, and metabolism of
polyamines. To confirm the expression dynamics of selected DEGs involved in
various pathways, experiments were set up to investigate the effects of hormones
(Indole-3-butytric acid, IBA; Kinetin, KT), polyamines, H2O2 and stresses on SE.
Our results showed that exogenous application of IBA and KT positively regulated
the development of EC and SEs, and that polyamines and H2O2 promoted the
conversion of EC into SEs. Furthermore, we found that low and moderate stress is
beneficial for proliferation of EC and SEs formation. Together, our global
analysis of transcriptomic dynamics reveals that hormone homeostasis, polyamines,
and stress response synergistically regulating SE in cotton.
PMID- 27511194
TI - Maternal Exposure to Occupational Asthmagens During Pregnancy and Autism Spectrum
Disorder in the Study to Explore Early Development.
AB - Maternal immune activity has been linked to children with autism spectrum
disorder (ASD). We examined maternal occupational exposure to asthma-causing
agents during pregnancy in relation to ASD risk. Our sample included 463 ASD
cases and 710 general population controls from the Study to Explore Early
Development whose mothers reported at least one job during pregnancy. Asthmagen
exposure was estimated from a published job-exposure matrix. The adjusted odds
ratio for ASD comparing asthmagen-exposed to unexposed was 1.39 (95 % CI 0.96
2.02). Maternal workplace asthmagen exposure was not associated with ASD risk in
this study, but this result does not exclude some involvement of maternal
exposure to asthma-causing agents in ASD.
PMID- 27511195
TI - Relationship Between Subtypes of Restricted and Repetitive Behaviors and Sleep
Disturbance in Autism Spectrum Disorder.
AB - We examined the association of two types of restricted and repetitive behaviors,
repetitive sensory motor (RSM) and insistence on sameness (IS), with sleep
problems in children with autism spectrum disorder (ASD). Participants included
532 children (aged 2-17) who participated in the Autism Speaks Autism Treatment
Network research registry. Confirmatory factor analysis of the Autism Diagnostic
Interview-Revised detected the presence of RSM and IS. RSM behaviors were
positively associated with parent-reported sleep problems, and this relationship
remained significant after controlling for anxiety symptoms. IS was not
significantly associated with sleep problems. Better understanding of the
relationship between specific types of repetitive behaviors and sleep problems
may allow providers to tailor interventions to the individual presentations of
their patients with ASD.
PMID- 27511193
TI - An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease.
AB - BACKGROUND: Epigenetic biomarkers of aging (the "epigenetic clock") have the
potential to address puzzling findings surrounding mortality rates and incidence
of cardio-metabolic disease such as: (1) women consistently exhibiting lower
mortality than men despite having higher levels of morbidity; (2) racial/ethnic
groups having different mortality rates even after adjusting for socioeconomic
differences; (3) the black/white mortality cross-over effect in late adulthood;
and (4) Hispanics in the United States having a longer life expectancy than
Caucasians despite having a higher burden of traditional cardio-metabolic risk
factors. RESULTS: We analyzed blood, saliva, and brain samples from seven
different racial/ethnic groups. We assessed the intrinsic epigenetic age
acceleration of blood (independent of blood cell counts) and the extrinsic
epigenetic aging rates of blood (dependent on blood cell counts and tracks the
age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower
intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African
Americans have lower extrinsic epigenetic aging rates than Caucasians and
Hispanics but no differences were found for the intrinsic measure. Men have
higher epigenetic aging rates than women in blood, saliva, and brain tissue.
CONCLUSIONS: Epigenetic aging rates are significantly associated with sex,
race/ethnicity, and to a lesser extent with CHD risk factors, but not with
incident CHD outcomes. These results may help elucidate lower than expected
mortality rates observed in Hispanics, older African-Americans, and women.
PMID- 27511196
TI - Reverse polyaxial less invasive stabilization systems for treatment of femoral
intertrochanteric fractures of the distal femur.
AB - INTRODUCTION: The reverse less invasive stabilization system (LISS) for the
distal femur remains generally regarded as a safe and satisfactory option for the
treatment of unstable proximal femoral fractures. The polyaxial LISS provides a
reverse plating technique that leverages the advantages of proximal screws by
allowing the adjustable locking screw to be better positioned and providing more
reliable fixation on the proximal femur compared with the standard axial LISS. To
assess this fixation method, a detailed evaluation of institutional outcomes of
femoral intertrochanteric fractures treated with reverse polyaxial LISS was
performed. MATERIALS AND METHODS: A total of 29 patients presenting with femoral
intertrochanteric fractures were treated with the reverse polyaxial LISS system
between January 2010 and March 2011. Patients were classified into stable and
unstable fracture groups according to the Orthopaedic Trauma Association's (OTA)
classification. Clinical data, including operative time, blood loss, radiological
records and complications, Harris Hip scores and Parker scores, were collected
and analyzed. RESULTS: There were no significant between-group differences in
age, sex, or American Society of Anesthesiologists score. Operative time and
blood loss were significantly higher in the unstable fracture group compared with
the stable fracture group. Four cases of fixation failure, consisting of one case
of A2.3, one case of A3.2 and two cases of A3.3, occurred 4-7 m postoperatively.
CONCLUSIONS: Treatment of femoral intertrochanteric fractures with unstable
pattern using polyaxial reverse LISS results in high failure rates; therefore, it
should not be recommended as a routine alternative method for the treatment of
femoral intertrochanteric fractures with unstable pattern.
PMID- 27511197
TI - Efficacy and safety of sofosbuvir plus simeprevir therapy in Egyptian patients
with chronic hepatitis C: a real-world experience.
AB - BACKGROUND: Simeprevir plus sofosbuvir (SIM/SOF) regimen was recommended by
professional guidelines for certain patients with HCV genotype 1 infection and
there is lack of data about this regimen in patients with genotype 4 infection.
AIM: To evaluate the efficacy and safety of this regimen in Egyptian patients
with chronic HCV genotype 4 infection in the real world. METHODS: Multicentre
observational study included 583 patients with HCV genotype 4 infection who began
12 weeks of treatment with SIM plus SOF. Demographic, clinical and virological
data as well as adverse outcomes were collected. Treatment naive patients were
342 (59%) of all included patients, 45% of patients had severe fibrosis (F3 and
F4) while 55% had mild fibrosis (F1 and F2) and the primary outcome was sustained
virological response (SVR). RESULTS: The overall SVR rate was 95.7% (558 out of
583 patients). In total, SVR12 in naive patients with mild fibrosis score (F1 and
F2) was achieved in 98.9% (94/95) for F1 and 98.1% (105/107) for F2, while naive
patients with severe fibrosis (F3 and F4) achieved SVR of 97.7% (86/88) for F3
and (42/52) 80.8% for F4. SVR in patients with previous interferon treatment
achieved in 100% (45/45) for patients with F1 and 98.7% (74/75) for F2. While
94.7% (72/76) in experienced patients with F3; and 88.9% (40/45) for F4 achieved
SVR12. Notable side effects included rash in 21 patients, photosensitivity in 18
patients, pruritus in 44 patients and hyperbilirubinemia in 42 patients.
CONCLUSIONS: A 12-week regimen of simeprevir/sofosbuvir was efficacious and well
tolerated by treatment-naive and treatment-experienced patients with chronic HCV
genotype 4.
PMID- 27511198
TI - Assessment of faecal microbial transfer in irritable bowel syndrome with severe
bloating.
PMID- 27511200
TI - CORR Insights(r): High Risk of Surgical Glove Perforation From Surgical Rotatory
Instruments.
PMID- 27511199
TI - RSPO3 expands intestinal stem cell and niche compartments and drives
tumorigenesis.
AB - OBJECTIVE: The gross majority of colorectal cancer cases results from aberrant
Wnt/beta-catenin signalling through adenomatous polyposis coli (APC) or CTNNB1
mutations. However, a subset of human colon tumours harbour, mutually exclusive
with APC and CTNNB1 mutations, gene fusions in RSPO2 or RSPO3, leading to
enhanced expression of these R-spondin genes. This suggested that RSPO activation
can substitute for the most common mutations as an alternative driver for
intestinal cancer. Involvement of RSPO3 in tumour growth was recently shown in
RSPO3-fusion-positive xenograft models. The current study determines the extent
into which solely a gain in RSPO3 actually functions as a driver of intestinal
cancer in a direct, causal fashion, and addresses the in vivo activities of RSPO3
in parallel. DESIGN: We generated a conditional Rspo3 transgenic mouse model in
which the Rspo3 transgene is expressed upon Cre activity. Cre is provided by
cross-breeding with Lgr5-GFP-CreERT2 mice. RESULTS: Upon in vivo Rspo3
expression, mice rapidly developed extensive hyperplastic, adenomatous and
adenocarcinomatous lesions throughout the intestine. RSPO3 induced the expansion
of Lgr5+ stem cells, Paneth cells, non-Paneth cell label-retaining cells and
Lgr4+ cells, thus promoting both intestinal stem cell and niche compartments.
Wnt/beta-catenin signalling was modestly increased upon Rspo3 expression and
mutant Kras synergised with Rspo3 in hyperplastic growth. CONCLUSIONS: We provide
in vivo evidence that RSPO3 stimulates the crypt stem cell and niche compartments
and drives rapid intestinal tumorigenesis. This establishes RSPO3 as a potent
driver of intestinal cancer and proposes RSPO3 as a candidate target for therapy
in patients with colorectal cancer harbouring RSPO3 fusions.
PMID- 27511201
TI - One-stage Revision With Catheter Infusion of Intraarticular Antibiotics
Successfully Treats Infected THA.
AB - BACKGROUND: Two-stage revision surgery for infected total hip arthroplasty (THA)
is commonly advocated, but substantial morbidity and expense are associated with
this technique. In certain cases of infected THA, treatment with one-stage
revision surgery and intraarticular infusion of antibiotics may offer a
reasonable alternative with the distinct advantage of providing a means of
delivering the drug in high concentrations. QUESTIONS/PURPOSES: We describe a
protocol for intraarticular delivery of antibiotics to the hip through an
indwelling catheter combined with one-stage revision surgery and examine (1) the
success as judged by eradication of infection at 1 year when treating chronically
infected cemented stems; (2) success in treating late-onset acute infections in
well-ingrown cementless stems; and (3) what complications were associated with
this approach in a small case series. METHODS: Between January 2002 and July
2013, 30 patients (30 hips) presented to the senior author for treatment of
infected THA. Of those, 21 patients (21 hips) with infected cemented THAs
underwent debridement and single-stage revision to cementless total hip implants
followed by catheter infusion of intraarticular antibiotics. Nine patients (nine
hips) with late-onset acute infections in cementless THA had bone-ingrown
implants. These patients were all more than 2 years from their original surgery
and had acute symptoms of infection for 4 to 9 days. Seven had their original THA
elsewhere, and two were the author's patients. All were symptom-free until the
onset of their infection, and none had postoperative wound complications, fever,
or prolonged pain suggestive of a more chronic process. They were treated with
debridement and head and liner exchange, again followed by catheter infusion of
intraarticular antibiotics. During this time period, this represented all
infected THAs treated by the senior author, and all were treated with this
protocol; no patient underwent two-stage exchange during this time, and no
patients were lost to followup. At the time of the surgery, two Hickman catheters
were placed in each hip to begin intraarticular delivery of antibiotics in the
early postoperative period. Antibiotics were infused daily into the hip for 6
weeks with the tubes used for infusion only. Eleven of the single-stage revisions
and four of the hips treated with debridement had methicillin-resistant
Staphylococcus aureus. Patients were considered free of infection if they had no
clinical signs of infection and had a normal C-reactive protein and erythrocyte
sedimentation rate at 1 year. Complications were ascertained by chart review.
RESULTS: Twenty of 21 (95%) infections in patients who had single-stage revision
for chronically infected cemented THA were apparently free from infection and
remained so at a mean followup of 63 months (range, 25-157 months). One case grew
Candida albicans in the operative cultures and remained free of signs of
infection after rerevision followed by infusion of fluconazole. The nine
cementless THAs treated with debridement and head/liner exchange all remained
free of signs of infection at a mean followup of 74 months (range, 62-121
months). Few complications were associated with the technique. Four patients had
elevated serum levels of vancomycin without renal function changes and two
patients had transient blood urea nitrogen/creatinine elevations with normal
vancomycin levels that resolved with dosage adjustments. No patient had evidence
of permanent renal damage. None of the patients in this study developed a chronic
fistula or had significant drainage from the catheter site. CONCLUSIONS: Single
stage revision for chronically infected cemented THA and debridement of bone
ingrown cementless THA with late-onset acute infection followed with indwelling
catheter antibiotic infusion can result in infection eradication even when
resistant organisms are involved. Larger study groups would better assess this
technique and prospective comparisons to more traditional one- and two-stage
revision techniques for infected THA will likely require multi-institutional
approaches. LEVEL OF EVIDENCE: Level IV, therapeutic study.
PMID- 27511202
TI - Are Recently Trained Tumor Fellows Performing Less Tumor Surgery? An Analysis of
10 Years of the ABOS Part II Database.
AB - BACKGROUND: The majority of orthopaedic trainees pursue additional subspecialty
training at the conclusion of residency. Although national trends indicate that
fellowship-trained surgeons are more frequently performing cases in their defined
subspecialties, this may not be the case for recently trained tumor fellows.
Prior work has established that low tumor case volume is a significant stressor
for recently trained tumor fellows. Given the relative rarity of musculoskeletal
tumors, it is important for prospective trainees to have clear expectations for
the proportion of specialty-specific procedures early during their careers. In
addition, knowledge of anticipated specialty case volume is important to optimize
fellowship training and to provide guidance for meeting the public health
requirements for orthopaedic oncology. QUESTIONS/PURPOSES: We wished to determine
(1) the number of examinees who self-reported tumor fellowship training during
the last decade; (2) how many tumor fellowship-educated surgeons did an
additional fellowship(s) in other subspecialties; (3) the number and proportion
of tumor, trauma, adult reconstruction, and other procedures performed by tumor
trained fellows; and (4) changes in the proportion of procedures performed by
tumor-trained fellows during the 10-year period of the study. METHODS: The
American Board of Orthopaedic Surgery Part II database was used to identify
examinees who reported tumor fellowship training between 2004 and 2013. All
submitted procedures were broadly categorized as "tumor," "trauma," "adult
reconstruction," or "other." Annual procedure volumes were calculated and
univariate analysis allowed comparison of categorized procedures during the
duration of the study. RESULTS: The median annual number of candidates reporting
tumor fellowship training was 12.5 (range, 7-16). There were 28 of 118 (24%)
candidates who reported additional fellowship training. A total of 14,718
procedures were performed by all candidates with tumor fellowship training during
the 10-year period of the study, 42% of which were categorized as tumor
procedures. Overall, only 36% of candidates reported tumor procedures making up
greater than 50% of their case volume. Between 2004 to 2005 and 2012 to 2013, the
proportion of tumor procedures decreased (45% versus 36%; p < 0.001), whereas the
number of adult reconstruction procedures increased (9% versus 19%; p < 0.001).
CONCLUSIONS: Between 2004 and 2013, only one-third of recently trained tumor
fellows had practices with tumor procedures accounting for greater than 50% of
their total case volume. Furthermore, the proportion of tumor cases performed by
recently trained tumor fellows decreased during the same time. The proportion of
specialty-specific procedures is lower in orthopaedic oncology than other
orthopaedic subspecialties, which is important information for current trainees
interested in orthopaedic oncology fellowship training and for orthopaedic
oncology educators. The findings in this study should serve as an initial
platform for further discussion regarding the optimal number of fellowship
trained orthopaedic oncologists required to meet regional and national needs for
an accessible and proficient work force.
PMID- 27511203
TI - Can Surgeons Adequately Capture Adverse Events Using the Spinal Adverse Events
Severity System (SAVES) and OrthoSAVES?
AB - BACKGROUND: Physicians have consistently shown poor adverse-event reporting
practices in the literature and yet they have the clinical acumen to properly
stratify and appraise these events. The Spine Adverse Events Severity System
(SAVES) and Orthopaedic Surgical Adverse Events Severity System (OrthoSAVES) are
standardized assessment tools designed to record adverse events in orthopaedic
patients. These tools provide a list of prespecified adverse events for users to
choose from-an aid that may improve adverse-event reporting by physicians.
QUESTIONS/PURPOSES: The primary objective was to compare surgeons' adverse-event
reporting with reporting by independent clinical reviewers using SAVES Version 2
(SAVES V2) and OrthoSAVES in elective orthopaedic procedures. METHOD: This was a
10-week prospective study where SAVES V2 and OrthoSAVES were used by six
orthopaedic surgeons and two independent, non-MD clinical reviewers to record
adverse events after all elective procedures to the point of patient discharge.
Neither surgeons nor reviewers received specific training on adverse-event
reporting. Surgeons were aware of the ongoing study, and reported adverse events
based on their clinical interactions with the patients. Reviewers recorded
adverse events by reviewing clinical notes by surgeons and other healthcare
professionals (such as nurses and physiotherapists). Adverse events were graded
using the severity-grading system included in SAVES V2 and OrthoSAVES. At
discharge, adverse events recorded by surgeons and reviewers were recorded in our
database. RESULTS: Adverse-event data for 164 patients were collected (48
patients who had spine surgery, 51 who had hip surgery, 34 who had knee surgery,
and 31 who had shoulder surgery). Overall, 99 adverse events were captured by the
reviewers, compared with 14 captured by the surgeons (p < 0.001). Surgeons
adequately captured major adverse events, but failed to record minor events that
were captured by the reviewers. A total of 93 of 99 (94%) adverse events reported
by reviewers required only simple or minor treatment and had no long-term adverse
effect. Three patients experienced adverse events that resulted in use of
invasive or complex treatment that had a temporary adverse effect on outcome.
CONCLUSION: Using SAVES V2 and OrthoSAVES, independent reviewers reported more
minor adverse events compared with surgeons. The value of third-party reviewers
requires further investigation in a detailed cost-benefit analysis. LEVEL OF
EVIDENCE: Level II, therapeutic study.
PMID- 27511205
TI - Correction to: Cytochrome P450 and Non-Cytochrome P450 Oxidative Metabolism:
Contributions to the Pharmacokinetics, Safety, and Efficacy of Xenobiotics.
PMID- 27511204
TI - Revascularization of acute basilar artery occlusion using the Tigertriever
adjustable clot retriever.
PMID- 27511206
TI - Gender-Specificity in Viewing Time Among Heterosexual Women.
AB - Measures of sexual interest tend to be more gender-specific in heterosexual men
than in heterosexual women. Cognitive measures, such as viewing time to
attractive stimuli, may also show similar patterns of gender-specificity or
nonspecificity among men and women and thus serve as useful adjuncts to more
direct measures of sexual interest. The objectives of the present research were
to determine the extent of gender-specificity in women's viewing times for female
pictures (varying in their perceived physical attractiveness) and explore the
influence of social comparison of physical appearance on these patterns of
responses. In Study 1, we recorded only women's viewing times for pictures of
both genders, measured self-reported menstrual cycle phase, and manipulated the
waist-to-hip ratio of the women in the female pictures. In Study 2, we recorded
women's and men's viewing times, self-reported sexual attraction to pictures of
males and females, and physical appearance social comparison. Study 1 found that
heterosexual women's viewing time toward female pictures was not associated with
manipulation of the perceived attractiveness of those pictures. Study 2 found
that heterosexual men were more gender-specific than heterosexual women in their
viewing time patterns. We also found that reported sexual attraction and physical
appearance social comparison were associated with heterosexual women's viewing
times for female pictures, while heterosexual men's viewing times were associated
with sexual attraction only. Our results are discussed in relation to the utility
of viewing time as an indicator of visual attention toward attractive or sexually
appealing visual stimuli.
PMID- 27511209
TI - Sexual Perfectionism in Women: Not as Simple as Adaptive or Maladaptive.
AB - According to research and theory, the construct of perfectionism may apply to
specific life domains, including being a perfect sexual partner. We extended the
research on sexual perfectionism (SP) by examining the relationships between its
various dimensions (i.e., self-directed, partner-directed, socially prescribed,
partner-prescribed) and communication about sex, sexual functioning, and
appearance self-consciousness during sex. Women (N = 208) of ages 19-50 were
recruited online to respond to the Multidimensional Sexual Perfectionism
Questionnaire and measures of communication about sex, sexual functioning, and
physical appearance self-consciousness during sex. Dimensions of SP demonstrated
a mixed pattern of relationships with measures of adaptive functioning. Partner
prescribed SP was related to greater appearance self-consciousness during sex,
indicating an unfavorable role of this dimension of SP. An indirect effect of
socially prescribed and partner-prescribed SP on sexual functioning through poor
dyadic communication about sex and greater appearance self-consciousness was also
found. Self-directed SP was less clearly problematic and uniquely related to
better dyadic communication, whereas partner-directed SP was uniquely related to
fewer concerns about the body appearance during sex. In conclusion, with respect
to personal functioning, higher standards directed towards sexual partners may be
less problematic but perceptions that romantic partners expect one to be a
perfect sexual partner may have deleterious effects. Overall, SP may relate to
sexual experiences of women beyond the college-age group with some aspects of SP
being more problematic than others.
PMID- 27511207
TI - Pubertal Stress and Nutrition and their Association with Sexual Orientation and
Height in the Add Health Data.
AB - A number of studies have indicated that gay men tend to be shorter, on average,
than heterosexual men. Less evidence exists that lesbian women are taller, on
average, than heterosexual women. The most popular explanation of the association
between sexual orientation and height involves prenatal factors, such that, for
example, gay men may have been exposed to lower than typical androgens during
fetal development, which impacts their height and sexual orientation as adults.
An alternative explanation involves stress, given that stress has been associated
with sexual minority identification and with lower height. Another alternative
explanation involves nutrition, although its relationship is less clear with
sexual minority identification. Using the Add Health data, which is a large,
nationally representative and longitudinal sample of American adolescents (n =
14,786), we tested a mediation model, such that sexual orientation -> pubertal
stress/nutrition -> height. Within men, we found that gay men (n = 126) were
shorter, on average, than heterosexual men (n = 6412). None of the 24 pubertal
stress-related and 15 pubertal nutrition-related variables assessed in the Add
Health data mediated the relationship between sexual orientation and height in
men. Within women, lesbians (n = 75) did not differ significantly in stature
compared to heterosexual women (n = 6267). Thus, prenatal mechanisms (e.g.,
hormones, maternal immune response) are likely better candidates for explaining
the height difference between gay men and heterosexual men.
PMID- 27511208
TI - Decisions About Testing for HIV While in a Relationship: Perspectives From an
Urban, Convenience Sample of HIV-Negative Male Couples Who Have a Sexual
Agreement.
AB - Many HIV-negative male couples establish a sexual agreement to help manage their
HIV risk; however, less is known about their decisions about testing in this
context. The present study examined whether male couples discussed HIV testing
and explored their decisions about testing in the context of their sexual
agreement at the individual- and couple-levels. Qualitative dyadic interview data
were collected from 29 HIV-negative male couples with a sexual agreement who
resided in Atlanta or Detroit; the sample was stratified by agreement type.
Content analysis revealed male couples' decisions about HIV testing as routine,
self-assurance, reliance and assumption on partner, beginning of relationship
testers, and/or trust; decisions varied between partners and by agreement type.
Findings suggest prevention efforts should help male couples integrate HIV
testing into their sexual agreement that matches their agreement type and
associated HIV-related risk behavior, and help shift their one-sided decisions
about testing to a couple's mutually shared decision.
PMID- 27511210
TI - miR-483-5p promotes growth, invasion and self-renewal of gastric cancer stem
cells by Wnt/beta-catenin signaling.
AB - Gastric carcinoma (GC) ranks as the second most common cause of cancer-associated
mortality worldwide. Emerging evidence has suggested a potential novel
therapeutic strategy based on the ability of cancer stem cells (CSCs) to trigger
tumorigenesis. MicroRNAs (miRNAs) have previously been implicated in CSC
formation and regulation of their functional characteristics. In the current
study, a significant upregulation of miR-483-5p levels was demonstrated in
spheroid body-forming cells (P<0.01) by reverse transcription-quantitative
polymerase chain reaction, which were isolated from the MKN-45 gastric cancer
cell line and possessed gastric CSC (GCSC) properties. An MTT assay demonstrated
that overexpression of miR-483-5p by transfection with miR-483-5p mimics
significantly increased cell proliferation and Annexin V-propidium iodide
staining indicated the suppression of cell apoptosis, suggesting that miR-483-5p
has an important function in GCSC growth. Notably, Transwell and sphere formation
assays demonstrated that miR-483-5p elevation promoted GCSC invasion and cell
self-renewal ability, respectively. Further western blotting assays demonstrated
that miR-483-5p upregulation induced an increase in the protein expression levels
of beta-catenin and its downstream target molecules, including cyclin D1, Bcl-2
and matrix metalloproteinase 2, indicating that miR-483-5p activates Wnt/beta
catenin signaling. Inhibition of this pathway by beta-catenin small interfering
RNA transfection attenuated the miR-483-5p-induced effects on cell growth,
invasion and self-renewal. These results demonstrate that miR-483-5p may act as
an oncogene to promote the development of GC by regulating GCSC growth, invasion
and self-renewal via the Wnt/beta-catenin signaling pathway. Thus, the present
study suggests that miR-483-5p may be a promising therapeutic target against GC.
PMID- 27511211
TI - Changes in testicular function proteins and sperm acrosome status in rats treated
with valproic acid.
AB - Valproic acid (VPA), an anti-epileptic drug, reduces testosterone levels and
sperm quality. However, the degree to which testosterone levels and sperm quality
are decreased under VPA treatment needs to be clarified. The aim of the present
study was to investigate the testicular proteins involved in testosterone
synthesis and spermatogenesis, histopathology and sperm acrosome status in VPA
treated rats. Adult rats were divided into control and experimental groups (n=8
in each). Rats in the experimental group were treated with 500mg kg-1, i.p., VPA
for 10 consecutive days. Expression of Ki-67, tyrosine phosphorylated proteins
and testicular steroidogenic proteins was examined. As expected, VPA-treated rats
exhibited adverse changes in almost all reproductive parameters, particularly an
increase in precocious acrosome reactions, compared with the control group. In
addition, fibrosis of the tunica albuginea and tubule basement membrane was
observed in testes from VPA-treated rats. Moreover, the expression of testicular
Ki-67, cholesterol side-chain cleavage enzyme (P450scc) and phosphorylated
proteins (41, 51 and 83 kDa) was decreased significantly in VPA-treated rats
compared with control. In contrast, the expression of steroidogenic acute
regulatory proteins in the VPA-treated group was significantly higher than in the
control group. In conclusion, VPA treatment changes the expression of testicular
proteins responsible for spermatogenesis and testosterone production, resulting
in male infertility.
PMID- 27511212
TI - Risk factors for morbidities and mortality in children following pneumonectomy.
AB - BACKGROUND AND OBJECTIVE: Pneumonectomy (PNE) is a procedure infrequently
performed in children. A high morbidity/mortality rate associated with PNE has
been described. Few series have been published in the last 15 years. Risk factors
associated with morbidity/mortality after PNE were evaluated. Indications,
course, survival and complications of PNE in children were also analized.
METHODS: In a case series of 51 children who underwent PNE, death within 30 days
of surgery, pneumonia, empyema, sepsis, adult respiratory distress syndrome,
bronchopleural fistula, bleeding, pneumothorax and post-PNE syndrome were
considered major morbidities. Scoliosis, wound infection and atelectasis were
considered minor morbidities. RESULTS: Median age at PNE was 7.4 years; 45% were
males. Indications of pneumonectomy were postinfectious bronchiectasis (61%),
tumours (17%), pulmonary malformations (17%), aspiration syndrome (14%), cystic
fibrosis (6%), immunodeficiency (4%) and trauma (2%). Mortality rate was 4% at 1
month. Major and minor morbidities were present in 23% and 27% of patients,
respectively. Risk factors for development of morbidities after PNE were age <= 3
years (OR: 16.7; 95% CI: 2.4-117) and the need for mechanical ventilation for at
least 4 days (OR: 8; 95% CI: 1.5-43.6). CONCLUSION: Children are at high risk of
death, major and minor morbidities following PNE. Caution is recommended for this
group of patients.
PMID- 27511213
TI - Malpractice claims related to tooth extractions.
AB - OBJECTIVE: The aim of this study was to analyze malpractice claims related to
tooth extractions in order to identify areas requiring emphasis and eventually to
reduce the number of complications. MATERIAL AND METHODS: We compiled a file of
all malpractice claims related to tooth extractions (EBA code) between 1997 and
2010 from the Finnish Patient Insurance Centre. We then examined the data with
respect to date, tooth, surgery, injury diagnosis, and the authority's decision
on the case. RESULTS: The material consisted of 852 completed patient cases. Most
of the teeth were third molars (66 %), followed by first molars (8 %), and second
molars (7 %). The majority of claims were related to operative extraction (71 %)
followed by ordinary extraction (17 %) and apicoectomy of a single-rooted tooth
(7 %) or multi-rooted tooth (2 %). The most common diagnosis was injury of the
lingual or inferior alveolar nerve. According to the authority's decision, the
patient received compensation more often in cases involving a third molar than
other teeth (56 vs. 46 %, P < 0.05). CONCLUSION: The removal of a mandibular
third molar was the basis for the majority of malpractice claims. CLINICAL
RELEVANCE: To reduce the numbers of lingual and inferior alveolar nerve injuries,
the removal of mandibular third molars necessitates recent and high-quality
panoramic radiograph, preoperative assessment of the difficulty of removal, and
consciousness of the variable anatomical course of the lingual nerve.
PMID- 27511214
TI - Prevalence of otologic signs and symptoms in adult patients with
temporomandibular disorders: a systematic review and meta-analysis.
AB - OBJECTIVE: This study aims to estimate the prevalence of otologic signs and
symptoms in adult patients with temporomandibular disorders (TMD). MATERIAL AND
METHODS: Search strategies were developed for each of the following databases:
PubMed, LILACS, Scopus, Web of Science, Proquest, LIVIVO, and Google Scholar and
OpenGrey was used to assess the grey literature. It was included in this review
only observational studies using either research diagnostic criteria (RDC)/TMD or
DC/TMD indexes were selected. The Critical Appraisal Checklist for Studies
Reporting Prevalence Data from the Joanna Briggs Institute was used to assess the
risk of bias of the included studies. A proportion random effects meta-analysis
was conducted within the eight included studies. RESULTS: Eight studies met the
eligibility criteria and were selected. All of the included studies used the
RDC/TMD and report associated otologic signs and symptoms. The studies were
clustered into groups based on prevalence for each individual sign or symptom.
The most prevalent otologic symptom associated with TMD was ear fullness (74.8 %
standard deviation (SD), 43.02 to 96.25 %; n = 50), followed by otalgia (55.1 %
SD, 31.78 to 77.30; n = 386), tinnitus (52.1 % SD, 38.43 to 65.74; n = 1293),
vertigo (40.8 % SD, 11.29 to 74.72; n = 374), and hearing loss (38.9 % SD, 2.83
to 85.46; n = 744). CONCLUSION: The prevalence of otologic signs and symptoms in
adult patients with TMD is high. The most prevalent otologic symptom in patient
adults with TMD is ear fullness. CLINICAL RELEVANCE: This study intends to
provide understanding over the prevalence of otologic signs and symptoms in TMD
cases in adults.
PMID- 27511215
TI - Sustained clinico-radiologic response to anti-cytotoxic T lymphocyte antigen 4
antibody therapy in metastatic myxoid liposarcoma.
AB - Rarity and heterogeneity of sarcomas pose significant challenges in terms of
developing new therapies. Therefore, efforts towards studying immunotherapy in
sarcomas may provide hope for effective control of this group of devastating
cancers. A sustained clinico-radiologic response to the anti-cytotoxic T
lymphocyte antigen 4 antibody ipilimumab in a patient with metastatic myxoid
liposarcoma is reported. Although the patient was treated with this agent for
metastatic melanoma, both his metastatic cancers - melanoma and sarcoma -
meaningfully responded to this agent. Consideration of enrolling patients in
immunotherapy trials using various immune checkpoint inhibitors, where available,
is of paramount importance, especially when facing advanced and/or refractory
sarcoma situation.
PMID- 27511216
TI - Potential drug-drug interactions in hospitalised haematological patients.
AB - Background Frequently, haematological patients undergo highly complex and
intensive treatment protocols, so a high risk of drug-drug interactions could be
expected. Objectives To determine prevalence of clinically relevant drug-drug
interactions, to identify the most frequent drug-drug interactions and associated
risk factors. Methods A prospective, observational and descriptive study was
carried out from November 2012 to February 2013. Twice a week, every patient's
treatment sheet was collected. Each medication list was screened through two
databases: Thomson MicromedexTM and Drug Interaction FactsTM. All identified
potential drug-drug interactions with a moderate or higher severity rating were
recorded. Summary statistics were used to describe patient and disease
characteristics, most often prescribed drugs, and frequency, types and
classification of drug-drug interactions. Multiple logistic regression models
were used to identify risk factors associated with drug-drug interactions.
Results A total of 2061 drug-drug interactions were detected in 317 treatment
sheets from 58 patients. The prevalence of treatment sheets with drug-drug
interactions by Micromedex and Drug Interaction Facts databases were 74.1% and
56.8%, respectively. Azole antifungals, immunosuppressive drugs, antiemetics,
antidepressants, acid suppressants and corticosteroids were the most frequent
involved drugs. In multivariate analysis, the main risk factor associated with
increased odds for drug-drug interactions was a higher number of non
antineoplastic drugs. Conclusions The prevalence of drug-drug interactions was
common, with immunosuppressant and azole antifungal agents being the most
commonly involved drugs. The factor having the greatest influence on drug-drug
interactions was a higher number of non-antineoplastic drugs.
PMID- 27511217
TI - Comparison of patellofemoral outcomes after TKA using two prostheses with
different patellofemoral design features.
AB - PURPOSE: The purpose of the present study was to compare the clinical and
radiographic results after TKA using two prostheses with different sagittal
patellofemoral design features, including outcomes related to compatibility of
the patellofemoral joint. METHODS: The clinical and radiographic results of 81
patients (100 knees) who underwent TKA using the specific prosthesis (group A)
were compared with those in a control group who underwent TKA using the other
prosthesis (group B). The presence of anterior knee joint pain, patellar
crepitation, and patellar clunk syndrome was also checked. RESULTS: The function
score and maximum flexion angle at the last follow-up were slightly better in
group A than those in group B (92.0 +/- 2.3 vs. 90.6 +/- 4.2) (133.6 degrees +/-
8.4 degrees vs. 129.6 degrees +/- 11.4 degrees ). Anterior knee pain was
observed in 6 knees and patellar crepitation in four knees in group A. In group
B, these symptoms were observed in 22 knees and 18 knees, respectively. There was
no patellar clunk syndrome in either group. The alignment was corrected with
satisfactory positioning of components. The patellar height remained unchanged
after TKA in the two groups. The differences between preoperative and
postoperative patellar tilt angle and patellar translation were small.
CONCLUSION: When comparing the clinical and radiographic results after TKA using
two prostheses with different sagittal patellofemoral design features, TKA using
the specific prosthesis provided satisfactory results with less clinical symptoms
related to the patellofemoral kinematics with TKA using the other prosthesis.
LEVEL OF EVIDENCE: III.
PMID- 27511218
TI - In vivo kinematic analysis of the glenohumeral joint during dynamic full axial
rotation and scapular plane full abduction in healthy shoulders.
AB - PURPOSE: The purpose of this study was to evaluate the kinematics of healthy
shoulders during dynamic full axial rotation and scapular plane full abduction
using three-dimensional (3D)-to-two-dimensional (2D) model-to-image registration
techniques. METHODS: Dynamic glenohumeral kinematics during axial rotation and
scapular plane abduction were analysed in 10 healthy participants. Continuous
radiographic images of axial rotation and scapular plane abduction were taken
using a flat panel radiographic detector. The participants received a computed
tomography scan to generate virtual digitally reconstructed radiographs. The
density-based digitally reconstructed radiographs were then compared with the
serial radiographic images acquired using image correlations. These 3D-to-2D
model-to-image registration techniques determined the 3D positions and
orientations of the humerus and scapula during dynamic full axial rotation and
scapular plane full abduction. RESULTS: The humeral head centre translated an
average of 2.5 +/- 3.1 mm posteriorly, and 1.4 +/- 1.0 mm superiorly in the early
phase, then an average of 2.0 +/- 0.8 mm inferiorly in the late phase during
external rotation motion. The glenohumeral external rotation angle had a
significant effect on the anterior/posterior (A/P) and superior/inferior (S/I)
translation of the humeral head centre (both p < 0.05). 33.6 +/- 15.6 degrees of
glenohumeral external rotation occurred during scapular plane abduction. The
humeral head centre translated an average of 0.6 +/- 0.9 mm superiorly in the
early phase, then 1.7 +/- 2.6 mm inferiorly in the late phase, and translated an
average of 0.4 +/- 0.5 mm medially in the early phase, then 1.6 +/- 1.0 mm
laterally in the late phase during scapular plane abduction. The humeral
abduction angle had a significant effect on the S/I and lateral/medial (L/M)
translation of the humeral head centre (both p < 0.05). CONCLUSION: This study
investigated 3D translations of the humerus relative to the scapula: during
scapular plane full abduction, the humerus rotated 33.6 degrees externally
relative to the scapula, and during external rotation motion in the adducted
position, the humeral head centre translated an average of 2.5 mm posteriorly.
Kinematic data will provide important insights into evaluating the kinematics of
pathological shoulders. For clinical relevance, quantitative assessment of
dynamic healthy shoulder kinematics might be a physiological indicator for the
assessment of pathological shoulders.
PMID- 27511219
TI - Variations in EGFR ctDNA Correlates to the Clinical Efficacy of Afatinib in Non
Small Cell Lung Cancer with Acquired Resistance.
AB - Monitoring of non small cell lung cancer (NSCLC) patients on afatinib after
acquired resistance to 1st generation tyrosine kinase inhibitors is important.
Circulating tumor DNA (ctDNA) offers an attractive means other than conventional
tissue biopsy to characterize real time dynamic changes of the disease. In our
study, we aim to ascertain the clinical value for ctDNA monitoring of NSCLC
patients with acquired resistance for afatinib treatment. 200 patients positive
for the activating epithermal growth factor receptor (EGFR) mutations were
recruited for the study. Baseline molecular profiling for L858R, Exon 19 deletion
and T790M were performed. Thereafter, serial blood samples were taken and
patients were assessed by overall survival (OS) to determine the usefulness of
ctDNA monitoring. At baseline, matched tumor biopsy and ctDNA analysis had a
concordance agreement of 93.5% for L858R and exon 19 deletion. We also determined
that a large proportion of patients had the drug resistance mutation T790M prior
to starting afatinib and these patients were linked to a worse survival outcome.
For patients that registered a drop in ctDNA levels after afatinib was
administered, we observed that their survival outcome was more favorable (hazard
ratio 1.56, (95% CI 1.04 to 2.43). ctDNA levels were mostly elevated after the
3rd sampling cycle. Our results suggest that ctDNA can be used to predict the
clinical benefits of afatinib treatment. Pre and post blood sampling aids to
identify patient groups that may benefit most from the treatment and ctDNA is
relatively sensitive to address the dynamic changes of the disease at the
molecular level.
PMID- 27511220
TI - Sixty seconds on . . . the NHS "reset".
PMID- 27511221
TI - Epigenetics: New insights into site-specific variations in RA and OA.
PMID- 27511270
TI - Critical features of acute stress-induced cross-sensitization identified through
the hypothalamic-pituitary-adrenal axis output.
AB - Stress-induced sensitization represents a process whereby prior exposure to
severe stressors leaves animals or humans in a hyper-responsive state to further
stressors. Indeed, this phenomenon is assumed to be the basis of certain stress
associated pathologies, including post-traumatic stress disorder and psychosis.
One biological system particularly prone to sensitization is the hypothalamic
pituitary-adrenal (HPA) axis, the prototypic stress system. It is well
established that under certain conditions, prior exposure of animals to acute and
chronic (triggering) stressors enhances HPA responses to novel (heterotypic)
stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels).
However, such changes remain somewhat controversial and thus, the present study
aimed to identify the critical characteristics of the triggering and challenging
stressors that affect acute stress-induced HPA cross-sensitization in adult rats.
We found that HPA cross-sensitization is markedly influenced by the intensity of
the triggering stressor, whereas the length of exposure mainly affects its
persistence. Importantly, HPA sensitization is more evident with mild than strong
challenging stressors, and it may remain unnoticed if exposure to the challenging
stressor is prolonged beyond 15 min. We speculate that heterotypic HPA
sensitization might have developed to optimize biologically adaptive responses to
further brief stressors.
PMID- 27511269
TI - Association between IRF6 and 8q24 polymorphisms and nonsyndromic cleft lip with
or without cleft palate: Systematic review and meta-analysis.
AB - BACKGROUND: We conducted a systematic review and meta-analysis of interferon
regulatory factor 6 and 8q24 polymorphisms with nonsyndromic cleft lip
with/without cleft palate (NSCL/P). METHODS: Data extraction was independently
performed by two reviewers. Genotypic effects of four polymorphisms from 31
studies were pooled separately by ethnicity using a mixed-effect logit model with
accounting for heterogeneity. RESULTS: For rs2235371, AA and GA carried,
respectively, 51% (95% confidence interval [CI], 37%-61%) and 42% (95% CI, 32%
50%) lower risks of NSCL/P than GG genotypes in Asians, but these genotypes were
not significant in Caucasians. For rs2013162, only AA was significant, that is,
carried 0.65 (95% CI, 0.52-0.82) times lower odds than CC in Caucasians but not
for Asians. For rs642961, AA and GA genotypes, respectively, carried 2.47 (95%
CI, 1.41-4.35) and 1.40 (95% CI, 1.12-1.75) times higher odds in Asian, and 2.03
(95% CI, 1.52-2.71) and 1.58 (95% CI, 1.37-1.82) times higher odds in Caucasians
compare with GG genotypes. For rs987525, AA and CA genotypes carried 2.27 (95%
CI, 1.43-3.60) and 1.34 (95% CI, 1.02-1.77) times higher odds in Asian, and 5.25
(95% CI, 3.98-6.91) and 2.13 (95% CI-1.82, 2.49) times higher odds in Caucasians,
and 1.42 (95% CI, 1.10-1.82) and 1.28 (95% CI, 1.09-1.50) times higher odds in
mixed ethnicities compared with CC genotypes. These variant effects remained
significant based on applying Bonferroni corrected-thresholds, except in the
mixed ethnicity. CONCLUSION: We show robust variant effects in NSCL/P.
Considering them with other genes and risk factors might be useful to improve
prediction of NSCL/P occurrence. Birth Defects Research (Part A) 106:773-788,
2016. (c) 2016 The Authors Birth Defects Research Part A: Clinical and Molecular
Teratology Published by Wiley Periodicals, Inc.
PMID- 27511271
TI - Elastic Carbon Aerogels Reconstructed from Electrospun Nanofibers and Graphene as
Three-Dimensional Networked Matrix for Efficient Energy Storage/Conversion.
AB - Three-dimensional (3D) all-carbon nanofibrous aerogels with good structural
stability and elasticity are highly desirable in flexible energy
storage/conversion devices. Hence, an efficient surface-induced co-assembly
strategy is reported for the novel design and reconstruction of electrospun
nanofibers into graphene/carbon nanofiber (CNF) composite aerogels (GCA) with
hierarchical structures utilizing graphene flakes as cross-linkers. The as
obtained GCA monoliths possess interconnected macropores and integrated
conductive networks, which exhibit high elasticity and great structural
robustness. Benefitting from the largely increased surface area and charge
transfer efficiency derived from the multi-form firm interconnections (including
pillaring, bridging and jointing) between graphene flakes and CNF ribs, GCA not
only reveals prominent capacitive performance as supercapacitor electrode, but
also shows excellent hydrogen evolution reaction activity in both acidic and
alkaline solutions as a 3D template for decoration of few-layered MoSe2
nanosheets, holding great potentials for energy-related applications.
PMID- 27511272
TI - Frequent Surfing on Social Health Networks is Associated With Increased Knowledge
and Patient Health Activation.
AB - BACKGROUND: The advent of the Internet has driven a technological revolution that
has changed our lives. As part of this phenomenon, social networks have attained
a prominent role in health care. A variety of medical services is provided over
the Internet, including home monitoring, interactive communications between the
patient and service providers, and social support, among others. This study
emphasizes some of the practical implications of Web-based health social networks
for patients and for health care systems. OBJECTIVE: The objective of this study
was to assess how participation in a social network among individuals with a
chronic condition contributed to patient activation, based on the Patient
Activation Measure (PAM). METHODS: A prospective, cross-sectional survey with a
retrospective component was conducted. Data were collected from Camoni, a Hebrew
language Web-based social health network, participants in the diabetes mellitus,
pain, hypertension, and depression/anxiety forums, during November 2012 to 2013.
Experienced users (enrolled at least 6 months) and newly enrolled received
similar versions of the same questionnaire including sociodemographics and PAM.
RESULTS: Among 686 participants, 154 of 337 experienced and 123 of 349 newly
enrolled completed the questionnaire. Positive correlations (P<.05) were found
between frequency and duration of site visits and patient activation, social
relationships, and chronic disease knowledge. Men surfed longer than women
(chi23=10.104, P<.05). Experienced users with diabetes surfed more than those
with other illnesses and had significantly higher PAM scores (mean, M=69.3,
standard deviation, SD=19.1, PAM level 4; Z=-4.197, P<.001) than new users
(M=62.8, SD=18.7, PAM level 3). Disease knowledge directly predicted PAM for all
users (beta=.26 and .21, respectively). Frequency and duration of social health
network use were correlated with increased knowledge about a chronic disease.
Experienced surfers had higher PAM than newly enrolled, suggesting that continued
site use may contribute to increased activation. CONCLUSIONS: Web-based social
health networks offer an opportunity to expand patient knowledge and increase
involvement in personal health, thereby increasing patient activation. Further
studies are needed to examine these changes on other aspects of chronic illnesses
such as quality of life and costs.
PMID- 27511273
TI - Bullous eosinophilic annular erythema.
PMID- 27511274
TI - Improving Long-Term Care Facility Disaster Preparedness and Response: A
Literature Review.
AB - Long-term care facilities (LTCFs) and their residents are especially susceptible
to disruptions associated with natural disasters and often have limited
experience and resources for disaster planning and response. Previous reports
have offered disaster planning and response recommendations. We could not find a
comprehensive review of studied interventions or facility attributes that affect
disaster outcomes in LTCFs and their residents. We reviewed articles published
from 1974 through September 30, 2015, that studied disaster characteristics,
facility characteristics, patient characteristics, or an intervention that
affected outcomes for LTCFs experiencing or preparing for a disaster. Twenty-one
articles were included in the review. All of the articles fell into 1 of the
following categories: facility or disaster characteristics that predicted
preparedness or response, interventions to improve preparedness, and health
effects of disaster response, most often related to facility evacuation. All of
the articles described observational studies that were heterogeneous in design
and metrics. We believe that the evidence-based literature supports 6 specific
recommendations for facilities, governmental agencies, health care communities
and academia. These include integrated and coordinated disaster planning, staff
training, careful consideration before governments order mandatory evacuations,
anticipation of the increased medical needs of LTCF residents following a
disaster, and the need for more outcomes research. (Disaster Med Public Health
Preparedness. 2017;11:140-149).
PMID- 27511276
TI - Major contribution of central pulmonary reservoir discharge to increased
pulmonary arterial diastolic blood flow after birth in near-term lambs.
AB - Recent fetal lamb data have suggested that the pulmonary trunk (PT) region
displays a reservoir function and that a pharmacologically induced fall in
pulmonary vascular resistance (PVR) increases and redistributes diastolic
discharge from this central pulmonary reservoir toward the lungs, thereby
producing a positive diastolic offset in the pulmonary arterial (PA) blood flow
profile. As a similar offset in PA flow characteristically occurs after birth,
this study tested the hypotheses that 1) central pulmonary reservoir discharge is
both redistributed toward the lungs and increased in magnitude during the birth
transition and 2) discharge from this reservoir constitutes a major component of
increased PA diastolic blood flow after birth. Six anesthetized near-term fetal
lambs were instrumented with PT, ductal and left PA transit-time flow probes, and
aortic, PT and left atrial catheters. Hemodynamic data were recorded in fetuses
and at regular intervals during 2-h mechanical ventilation following cesarean
section delivery. Diastolic PA blood flow rose from near zero in fetuses to 468
+/- 188 ml/min by 15 min (P < 0.001). Central pulmonary reservoir discharge in
fetuses (99 +/- 44 ml/min) passed primarily right-to-left across the ductus.
However, this reservoir discharge redistributed entirely to the lungs by 1 min
after birth, and then doubled to a peak of 214 +/- 167 ml/min at 15 min (P <
0.001). Reservoir discharge subsequently stabilized at 151 +/- 60 ml/min at 30
120 min, which comprised ~50% of diastolic and ~20% of mean PA blood flow. These
findings suggest that enhanced diastolic central pulmonary reservoir discharge
plays a major role in supporting an increased pulmonary perfusion after birth.
PMID- 27511275
TI - Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of
non-syndromic orofacial cleft.
AB - We hypothesized that microRNA binding site single nucleotide polymorphisms (SNPs)
in fibroblast growth factors (FGFs) and their receptor genes (FGFRs) may affect
microRNA and mRNA interactions and are thereby associated with susceptibility of
non-syndromic orofacial cleft (NSOC). Ten SNPs among the FGF and FGFR genes were
selected and their associations with NSOC susceptibility were investigated in a
case-control study of 602 patients with NSOC and 605 healthy controls.
FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 showed suggestive association
with NSOC susceptibility. In the combination analysis, the observed odds ratios
(ORs) decreased with the number of protective alleles (rs1048201-T, rs3733336-G
and rs546782-T) but were not statistically significant beyond the first
comparison. Hsa-miRNA-496, hsa-miRNA-145 and hsa-miRNA-187 were predicted to be
miRNAs with binding sites within/near these SNPs and were expressed in lip
tissues. Decreased FGF2, FGF5 and FGF9 expression was observed in three cell
lines transfected with the corresponding miRNAs. Moreover, the three SNPs could
contribute to differential binding efficacy between hsa-miRNA-496 and FGF2, hsa
miRNA-145 and FGF5, hsa-miRNA-187 and FGF9 in luciferase assay. The results
suggest that FGF2/rs1048201, FGF5/rs3733336 and FGF9/rs546782 are associated with
the risk of NSOC and that these miRNA-FGF interactions may affect NSOC
development.
PMID- 27511278
TI - Sustained increases in blood pressure elicited by prolonged face cooling in
humans.
AB - We tested the hypothesis that increases in blood pressure are sustained
throughout 15 min of face cooling. Two independent trials were carried out. In
the Face-Cooling Trial, 10 healthy adults underwent 15 min of face cooling where
a 2.5-liter bag of ice water (0 +/- 0 degrees C) was placed over their cheeks,
eyes, and forehead. The Sham Trial was identical except that the temperature of
the water was 34 +/- 1 degrees C. Primary dependent variables were forehead
temperature, mean arterial pressure, and forearm vascular resistance. The square
root of the mean of successive differences in R-R interval (RMSSD) provided an
index of cardiac parasympathetic activity. In the Face Cooling Trial, forehead
temperature fell from 34.1 +/- 0.9 degrees C at baseline to 12.9 +/- 3.3 degrees
C at the end of face cooling (P < 0.01). Mean arterial pressure increased from 83
+/- 9 mmHg at baseline to 106 +/- 13 mmHg at the end of face cooling (P < 0.01).
RMSSD increased from 61 +/- 40 ms at baseline to 165 +/- 97 ms during the first 2
min of face cooling (P <= 0.05), but returned to baseline levels thereafter (65
+/- 49 ms, P >= 0.46). Forearm vascular resistance increased from 18.3 +/- 4.4
mmHg.ml-1.100 g tissue-1.min at baseline to 26.6 +/- 4.0 mmHg.ml-1.100 g tissue
1.min at the end of face cooling (P < 0.01). There were no changes in the Sham
Trial. These data indicate that increases in blood pressure are sustained
throughout 15 min of face cooling, and face cooling elicits differential time
dependent parasympathetic and likely sympathetic activation.
PMID- 27511277
TI - Post-oral sugar detection rapidly and chemospecifically modulates taste-guided
behavior.
AB - Several recent studies have shown that post-oral sugar sensing rapidly stimulates
ingestion. Here, we explored the specificity with which early-phase post-oral
sugar sensing influenced ingestive motivation. In experiment 1, rats were trained
to associate the consumption of 0.3 M sucrose with injections of LiCl (3.0 meq/kg
ip, conditioned taste aversion) or given equivalent exposures to the stimuli, but
in an unpaired fashion. Then, all rats were subjected to two brief-access tests
to assess appetitive and consummatory responses to the taste properties of
sucrose (0.01-1.0 M), 0.12 M NaCl, and dH2O (in 10-s trials in randomized
blocks). Intraduodenal infusions of either 0.3 M sucrose or equiosmolar 0.15 M
NaCl (3.0 ml) were administered, beginning just before each test. For unpaired
rats, intraduodenal sucrose specifically enhanced licking for 0.03-1.0 M sucrose,
with no effect on trial initiation, relative to intraduodenal NaCl. Rats with an
aversion to sucrose suppressed licking responses to sucrose in a concentration
dependent manner, as expected, but the intraduodenal sucrose preload did not
appear to further influence licking responses; instead, intraduodenal sucrose
attenuated trial initiation. Using a serial taste reactivity (TR) paradigm,
however, experiment 2 demonstrated that intraduodenal sucrose preloads suppressed
ingestive oromotor responses to intraorally delivered sucrose in rats with a
sucrose aversion. Finally, experiment 3 showed that intraduodenal sucrose
preloads enhanced preferential licking to some representative tastants tested
(sucrose, Polycose, and Intralipid), but not others (NaCl, quinine). Together,
the results suggest that the early phase-reinforcing efficacy of post-oral sugar
is dependent on the sensory and motivational properties of the ingesta.
PMID- 27511279
TI - Heart rate variability during high heat stress: a comparison between young and
older adults with and without Type 2 diabetes.
AB - We examined whether older individuals with and without Type 2 diabetes (T2D)
experience differences in heart rate variability (HRV) during a 3-h exposure to
high heat stress compared with young adults. Young (Young; n = 22; 23 +/- 3 yr)
and older individuals with (T2D; n = 11; 59 +/- 9 yr) and without (Older; n = 25;
63 +/- 5 yr) T2D were exposed to heat stress (44 degrees C, 30% relative
humidity) for 3 h. Fifty-five HRV measures were assessed for 15 min at baseline
and at minutes 82.5-97.5 (Mid) and minutes 165-180 (End) during heat stress. When
compared with Young, a similar number of HRV indices were significantly different
(P < 0.05) in Older (Baseline: 35; Mid: 29; End: 32) and T2D (Baseline: 31; Mid:
30; End: 27). In contrast, the number of HRV indices significantly different (P <
0.05) between Older and T2D were far fewer (Baseline: 13, Mid: 1, End: 3). Within
group analyses demonstrated a greater change in the Young group's HRV during heat
stress compared with Older and T2D; the number of significantly different (P <
0.05) HRV indices between baseline and End were 42, 29, and 20, for Young, Older,
and T2D, respectively. Analysis of specific HRV domains suggest that the Young
group experienced greater sympathetic activity during heat stress compared with
Older and T2D. In conclusion, when compared with young, older individuals with
and without T2D demonstrate low HRV at baseline and less change in HRV (including
an attenuated sympathetic response) during 3 h high heat stress, potentially
contributing to impaired thermoregulatory function.
PMID- 27511280
TI - Sex differences in obesity-induced hypertension and vascular dysfunction: a
protective role for estrogen in adipose tissue inflammation?
AB - Obesity is a potent predictor of cardiovascular disease and associated risk
factors, including hypertension. Systemic inflammation has been suggested by a
number of studies to be an important link between excess adiposity and
hypertension, yet the majority of the studies have been conducted exclusively in
males. This is problematic since women represent ~53% of hypertensive cases and
are more likely than men to be obese. There is a growing body of literature
supporting a central role for immune cell activation in numerous experimental
models of hypertension, and both the sex of the subject and the sex of the T cell
have been shown to impact blood pressure (BP) responses to hypertensive stimuli.
Moreover, sex steroid hormones play an important role in energy homeostasis, as
well as in the regulation of immune responses; estrogen, in particular, has a
well-known impact on both cardiovascular and metabolic disorders. Therefore, the
purpose of this review is to examine whether sex or sex hormones regulate the
role of the immune system in the development of hypertension and related vascular
dysfunction in response to metabolic changes and stimuli, including a high-fat
diet.
PMID- 27511281
TI - alpha4-Containing nicotinic receptors contribute to the effects of perinatal
nicotine on ventilatory and metabolic responses of neonatal mice to ambient
cooling.
AB - Among numerous studies, perinatal nicotine exposure (PN) has had variable effects
on respiratory control in the neonatal period. The effects of acute nicotine
exposure on breathing are largely mediated by alpha4-containing nicotine
acetylcholine receptors (nAChRs). These receptors are also involved in
thermoregulatory responses induced by both acetylcholine and nicotine. We
therefore hypothesized that alpha4-containing nAChRs would mediate the effects of
PN on the metabolic and ventilatory responses of neonates to modest cold
exposure. Wild-type (WT) and alpha4 knockout (KO) mice were exposed to 6 mg.kg
1.day-1 nicotine or vehicle from embryonic day 14 At postnatal day (P) 7 mice
were cooled from an ambient temperature (TA) of 32 to 20 degrees C. Body
temperature (TB), rate of O2 consumption (Vo2), ventilation (Ve), respiratory
frequency (FB), and tidal volume (VT) were continually monitored. An absence of
alpha4 had no effect on the metabolic response to ambient cooling. Surprisingly,
PN selectively increased the metabolic response of KO pups to cooling.
Regardless, KO pups became hypothermic to the same degree as WT pups, and for
both genotypes the drop in TB was exacerbated by PN. PN led to hyperventilation
in WT pups caused by an increase in VT, an effect that was absent in alpha4 KO
littermates. We show that PN interacts with alpha4-containing nAChRs in unique
ways to modulate the control of breathing and thermoregulation in the early
postnatal period.
PMID- 27511282
TI - Oxytocin redux.
PMID- 27511283
TI - Effects of estrogen replacement on stress-induced cardiovascular responses via
renin-angiotensin system in ovariectomized rats.
AB - The purpose of this study was to determine whether chronic estrogen replacement
in ovariectomized rats inhibits the pressor response to psychological stress by
attenuating the activation of the renin-angiotensin system. Female Wistar rats
aged 9 wk were ovariectomized. After 4 wk, the rats were randomly assigned to be
implanted subcutaneously with pellets containing either 17beta-estradiol (E2) or
placebo (Pla). After 4 wk of treatment, the rats underwent cage-switch stress
and, in a separate experiment, a subset received an infusion of angiotensin II.
The cage-switch stress rapidly elevated blood pressure (BP) and heart rate (HR)
as measured by radiotelemetry in both groups. However, the BP and HR responses to
the stress were significantly attenuated in the E2 group compared with the Pla
group. An angiotensin II type 1 receptor blocker, losartan, given in drinking
water, abolished the difference in the pressor response to stress between the two
groups. Moreover, the stress-induced elevation in plasma renin activity and
angiotensin II concentration was significant in the Pla group, but not in the E2
group. In addition, the expression of renin mRNA in the kidney was lower in the
E2 group relative to the Pla group. Finally, we found that intravenous
angiotensin II infusion increased BP and decreased HR to a similar degree in both
groups. These results suggest that the inhibitory effects of estrogen on
psychological stress-induced activation of the renin-angiotensin system could be
at least partially responsible for the suppression of the pressor responses to
psychological stress seen in estrogen-replaced ovariectomized rats.
PMID- 27511285
TI - Comparison of neoadjuvant versus a surgery first approach for gastric and
esophagogastric cancer.
AB - Gastric cancer remains a significant worldwide health concern. While surgery is
required for cure, all but the earliest of cancers will require multimodality
therapy. Chemotherapy and chemoradiation in the neoadjuvant and adjuvant settings
have shown to improve overall survival, but the sequencing of treatment is
controversial. As healthcare expenses surge, it is increasingly important to
impart value to these treatments. This review will look at the intersection of
effective treatment and costs for gastric cancer. J. Surg. Oncol. 2016;114:296
303. (c) 2016 Wiley Periodicals, Inc.
PMID- 27511284
TI - A qualitative investigation of recovery after femoral fracture in Rett syndrome.
AB - BACKGROUND: Children with severe disability often develop osteoporosis and have
an increased risk of fracture. In Rett syndrome, the prevalence of fracture is
four times greater than in the general population, and the femur is commonly
affected. This study used qualitative methods to investigate the regaining of
mobility within 12 months following femoral fracture in Rett syndrome and parent
caregiver experiences. METHODS: Caregivers (n = 14) of cases registered with the
Australian Rett Syndrome Database with a daughter with Rett syndrome were
recruited if their daughter sustained a femoral fracture between 2009 and 2014.
Median (interquartile range) age at fracture was 11 years and 4 months (8 years
and 8 months to 22 years and 3 months). Qualitative methods were used to
investigate parent/caregiver experiences and their daughter's recovery following
fracture. Themes in the interview data were identified with thematic analysis.
RESULTS: Operative management was chosen for those walking independently and non
operative management for most of the remaining. All who walked independently and
one of the four who required assistance recovered pre-operative walking skills
within 6 months. Themes identified by caregivers related to the complexities of
pain recognition, the caregiver emotional journey and later rebuilding of
relationships with service providers. CONCLUSIONS: Those who walked with
assistance were vulnerable to loss of this skill. Difficulties in pain
recognition increased time to diagnose fracture, and the acute episode was
associated with heightened caregiver stress. Service providers can use family
centred practice models to support the strengthening of family functioning
following this acute event that is surprisingly common in those with severe
disability.
PMID- 27511286
TI - Terazulene Isomers: Polarity Change of OFETs through Molecular Orbital
Distribution Contrast.
AB - Intermolecular orbital coupling is fundamentally important to organic
semiconductor performance. Recently, we reported that 2,6':2',6"-terazulene
(TAz1) exhibited excellent performance as an n-type organic field-effect
transistor (OFET) via molecular orbital distribution control. To validate and
develop this concept, here we present three other terazulene regioisomers, which
have three azulene molecules connected at the 2- or 6-position along the long
axis of the azulene, thus constructing a linear expanded pi-conjugation system:
2,2':6',2"-terazulene (TAz2), 2,2':6',6"-terazulene (TAz3), and 6,2':6',6"
terazulene (TAz4). TAz2 and TAz3 exhibit ambipolar characteristics; TAz4 exhibits
clear n-type transistor behavior as an OFET. The lowest unoccupied molecular
orbitals (LUMOs) of all terazulenes are fully delocalized over the entire
molecule. In contrast, the highest occupied molecular orbitals (HOMOs) of TAz2
and TAz3 are delocalized over the 2,2'-biazulene units; the HOMOs of TAz4 are
localized at one end of the azulene unit. These findings confirm that terazulene
isomers which are simple hydrocarbon compounds are versatile materials with a
tunable-polarity FET characteristic that depends on the direction of the azulene
unit and the related contrast of the molecular orbital distribution in the
terazulene backbone.
PMID- 27511287
TI - Aligning Spinoza with Descartes: An informed Cartesian account of the truth bias.
AB - There is a bias towards believing information is true rather than false. The
Spinozan account claims there is an early, automatic bias towards believing. Only
afterwards can people engage in an effortful re-evaluation and disbelieve the
information. Supporting this account, there is a greater bias towards believing
information is true when under cognitive load. However, developing on the
Adaptive Lie Detector (ALIED) theory, the informed Cartesian can equally explain
this data. The account claims the bias under load is not evidence of automatic
belief; rather, people are undecided, but if forced to guess they can rely on
context information to make an informed judgement. The account predicts, and we
found, that if people can explicitly indicate their uncertainty, there should be
no bias towards believing because they are no longer required to guess. Thus, we
conclude that belief formation can be better explained by an informed Cartesian
account - an attempt to make an informed judgment under uncertainty.
PMID- 27511288
TI - Observation of intrinsic emission in beta-BiNbO4 available for excitation of both
UV light and high energy irradiation.
AB - beta-BiNbO4 with a high temperature triclinic form was prepared via a high
temperature solid-state reaction ceramic method. Structural refinement and
surface characteristic studies were performed. The optical absorption, and
electronic calculation of the band structures and density of states were also
studied. beta-BiNbO4 ceramic has an indirect transition with a band energy of
3.05 eV. The valence band is dominated by O-2p states whereas the conduction band
has predominantly Nb 4d and Bi 6s character. The intrinsic luminescence
properties of beta-BiNbO4 were reported, and present a blue emission band peak at
435 nm under the excitation of UV light. The beta-BiNbO4 ceramic presents
scintillation properties under high energy irradiation. The luminescence was
studied via the combinations of the color centers, band calculation and energy
transfer from NbO6 to Bi(3+) in the lattices. The thermal quenching and
activation energy for the luminescence were reported. beta-BiNbO4 has potential
applications in photoluminescence and scintillation materials.
PMID- 27511290
TI - Self-assembled vesicles of urea-tethered foldamers as hydrophobic drug carriers.
AB - Molecular self-assembly of nonamphiphilic alpha,beta-hybrid foldamers based on
urea-tethered anthranilic acid-proline (Ant-Pro) foldamers is reported. These
self-assembled hollow vesicular architectures can take up and release the
anticancer hydrophobic drug curcumin.
PMID- 27511289
TI - Evaluation of Substituted 1,2,3-Dithiazoles as Inhibitors of the Feline
Immunodeficiency Virus (FIV) Nucleocapsid Protein via a Proposed Zinc Ejection
Mechanism.
AB - A diverse library of 5-thieno-, 5-oxo-, and 5-imino-1,2,3-dithiazole derivatives
was synthesized and evaluated for efficacy against the feline immunodeficiency
virus (FIV) as a model for HIV in cells. Several diverse compounds from this
series displayed nanomolar activity and low toxicity, representing a potential
new class of compounds for the treatment of FIV and HIV.
PMID- 27511291
TI - TE-domestication and horizontal transfer in a putative Nef-AP1mu mimic of HLA-A
cytoplasmic domain re-trafficking.
AB - Genes of the major histocompatibility complex (MHC; also called HLA in human) are
polymorphic elements in the genomes of sharks to humans. Class-I and class-II MHC
loci appear responsible for much of the genetic linkage to myriad disease states
via the capacity to bind short (~8-15 a.a.) peptides of a given pathogen's
proteome, or in some cases, the altered proteomes of cancerous cells, and even
(in autoimmunity) certain nominal 'self' peptides (Janeway, 2004).(1)
Unfortunately, little is known about how the canonical structure of the MHC-I/-II
peptide-presenting gene evolved, particularly since beyond ~500 Mya (sharks) no
paralogs exist.(2,3) We previously reported that HLA-A isotype alleles with the
alpha1-helix, R65 motif, are wide-spread in phylogeny, but that the alpha 2
helix, H151R motif, has apparently segregated out of most species. Surprisingly,
an uncharacterized orf in T. syrichta (Loc-103275158) encoded R151, but within a
truncated A-23 like gene containing 5'- and 3'- footprints of the transposon
(TE), tigger-1; the extant tarsier A-23 allele is totally missing exon-3 and part
of exon-4; together, suggesting TE-mediated inactivation of an intact/ancestral A
23 allele (Murray, 2015a).(4) The unique Loc-103275158 orf encodes a putative 15
exon transcript with no apparent paralogs throughout phylogeny. However, an HLA
A11 like gene in M. leucophaeus with a shortened C-terminal domain, and an HLA-A
like orf in C. atys with two linked alpha1/alpha2/alpha3 domains, both contain a
second transmembrane segment, which is conserved in Loc-103275158. Thus, we could
model the putative protein with its Nef-like tail domain docked to its MHC-I like
alpha3 domain (i.e., on the same side of a membrane). This modeled tertiary
structure is strikingly similar to the solved structure of the Nef:MHC-I CD:AP1mu
transporter (Jia, 2012).(5) Nef:AP1mu binds the CD of MHC-I in trafficking MHC-I
away from the trans-golgi and into the endocytic pathway in HIV-1 infected cells.
The CD loop of the Loc-103275158 provisional protein conserved the nominal MHC-I
CD tyrosine phosphorylation site, and it has an N-terminal SH3 domain that we
docked in one conformation to its internal Nef-like domain. Here, we suggest that
phosphorylation of the protein's CD-loop signals an exchange between the internal
Nef-like domain and a lentiviral-Nef for binding the N-terminal SH3 domain -
freeing the Nef-like domain to bind MHC-I CD. Since the 5'-tigger sequence
encodes part of the pseudo alpha1/alpha2 MHC-I domain, and the 3'-tigger part of
the Nef-like domain, we speculate that transposition proceeded phylogenetically
disparate horizontal transfers, involving adjacent 5'- and 3'- parasitic
footprints, which we also found in the Loc-103275158 orf.
PMID- 27511292
TI - Cognitive Biases for Social Alcohol-Related Pictures and Alcohol Use in Specific
Social Settings: An Event-Level Study.
AB - BACKGROUND: Alcohol use occurs mainly among friends, in social contexts, and for
social reasons. Moreover, cognitive biases, such as attentional and approach
biases, have repeatedly been associated with alcohol use. This study aimed to
test whether nondependent drinkers display cognitive biases for social alcohol
related (SA) pictures and whether these biases are associated with alcohol use in
social drinking contexts. METHODS: The visual dot probe task and stimulus
response compatibility tasks were used to measure attentional and approach biases
for alcohol-related pictures at baseline. Event-level alcohol use was measured
using Ecological Momentary Assessments via personal smartphones. One hundred and
ninety-two young adults (51.6% men; Mage = 20.73) completed the study, resulting
in 11,257 assessments conducted on Thursday, Friday, and Saturday evenings for 5
consecutive weeks. RESULTS: While no overall attentional bias for alcohol-related
pictures was found, young adults showed an approach bias for both social and
nonsocial alcohol-related pictures. Multilevel models revealed no direct
association between cognitive biases for alcohol-related pictures and alcohol
use. However, higher levels of attentional bias for SA pictures were associated
with more drinking when individuals were surrounded by a greater number of
friends of opposite gender. Higher levels of an approach bias for SA pictures
were associated with more drinking in women surrounded by a greater number of
friends of the same gender. CONCLUSIONS: In a nondependent sample, cognitive
biases for SA pictures could not be associated with drinking directly. However, a
cognitive bias for SA pictures moderated the association between alcohol use and
number of friends present. As most observed effects were gender and situation
specific, replication of these effects is warranted.
PMID- 27511293
TI - Click-Chemistry Based Allergen Arrays Generated by Polymer Pen Lithography for
Mast Cell Activation Studies.
AB - The profiling of allergic responses is a powerful tool in biomedical research and
in judging therapeutic outcome in patients suffering from allergy. Novel insights
into the signaling cascades and easier readouts can be achieved by shifting
activation studies of bulk immune cells to the single cell level on patterned
surfaces. The functionality of dinitrophenol (DNP) as a hapten in the induction
of allergic reactions has allowed the activation process of single mast cells
seeded on patterned surfaces to be studied following treatment with allergen
specific Immunoglobulin E antibodies. Here, a click-chemistry approach is applied
in combination with polymer pen lithography (PPL) to pattern DNP-azide on alkyne
terminated surfaces to generate arrays of allergen. The large area
functionalization offered by PPL allows an easy incorporation of such arrays into
microfluidic chips. In such a setup, easy handling of cell suspension, incubation
process, and read-out by fluorescence microscopy will allow immune cell
activation screening to be easily adapted for diagnostics and biomedical
research.
PMID- 27511295
TI - Odor-induced recall of emotional memories in PTSD-Review and new paradigm for
research.
AB - It is clinically well known that olfactory intrusions in PTSD can be a disabling
phenomena due to the involuntary recall of odor memories. Odorants can trigger
involuntary recall of emotional memories as well have the potential to help
diminishing emotional arousal as grounding stimuli. Despite major advances in our
understanding of the function of olfactory system, the study of the relation of
olfaction and emotional memory is still relatively scarce. Odor memory is long
thought to be different than other types of memories such as verbal or visual
memories, being more strongly engraved and more closely related to strong
emotions. Brain areas mediating smell memory including orbitofrontal cortex and
other parts of medial prefrontal cortex, hippocampus and amygdala, have been
implicated in learning and memory and are part of a neural circuitry that is
involved in PTSD. The olfactory cortex itself also plays an important role in
emotional processing. Clinical observations support the notion that odor-evoked
memories can play a role in the symptomatology of PTSD. This paper reviews a re
emerging body of science linking odor processing to emotional processing in PTSD
using the calming and grounding effect of odors as well as the use of odors in
augmented exposure therapy. This results in converging evidence that olfaction is
an excellent model for studying many questions germane to the field of human
emotional memory processing.
PMID- 27511296
TI - The novel model peptide, alphaAL14, regulates angiogenesis by inhibiting VEGFR 2
mediated signaling in HUVECs.
AB - Inhibition of angiogenesis has been focused on as a strategy for treating several
diseases including cancer. In this study, a novel model peptide alphaAL14 was
synthesized and used to identify its inhibitory effects on angiogenesis. The anti
angiogenic effects of alphaAL14 were investigated using vascular endothelial
cells, HUVECs. alphaAL14 inhibited critical angiogenic processes including tubule
formation, cell migration and cell invasion with no influence on cell
proliferation in HUVECs. Activity of VEGFR2 was inhibited by alphaAL14 treatment
in HUVECs. Additionally, activities of major subsequent downstream factors of
VEGFR2 such as ERK, FAK and Akt were decreased. alphaAL14 affected expression of
Rac1, Cdc42, Arp2 and WAVE2 which are involved in formation of lamellipodia.
Moreover, alphaAL14 reduced NF-kappaB that can promote expression of several
genes relating to cell invasion such as MMP2 and MMP9. Therefore, the results
suggest that alphaAL14 has a potential to be developed as anti-angiogenic drug
for treating diseases driven by abnormal angiogenesis.
PMID- 27511297
TI - Multimodal MRI reveals structural connectivity differences in 22q11 deletion
syndrome related to impaired spatial working memory.
AB - INTRODUCTION: Impaired spatial working memory is a core cognitive deficit
observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested
as a candidate endophenotype for schizophrenia. However, to date, the
neuroanatomical mechanisms describing its structural and functional underpinnings
in 22q11DS remain unclear. We quantitatively investigate the cognitive processes
and associated neuroanatomy of spatial working memory in people with 22q11DS
compared to matched controls. We examine whether there are significant between
group differences in spatial working memory using task related fMRI, Voxel based
morphometry and white matter fiber tractography. MATERIALS AND METHODS:
Multimodal magnetic resonance imaging employing functional, diffusion and
volumetric techniques were used to quantitatively assess the cognitive and
neuroanatomical features of spatial working memory processes in 22q11DS. Twenty
six participants with genetically confirmed 22q11DS aged between 9 and 52 years
and 26 controls aged between 8 and 46 years, matched for age, gender, and
handedness were recruited. RESULTS: People with 22q11DS have significant
differences in spatial working memory functioning accompanied by a gray matter
volume reduction in the right precuneus. Gray matter volume was significantly
correlated with task performance scores in these areas. Tractography revealed
extensive differences along fibers between task-related cortical activations with
pronounced differences localized to interhemispheric commissural fibers within
the parietal section of the corpus callosum. CONCLUSIONS: Abnormal spatial
working memory in 22q11DS is associated with aberrant functional activity in
conjunction with gray and white matter structural abnormalities. These anomalies
in discrete brain regions may increase susceptibility to the development of
psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689-4705, 2016.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27511294
TI - The need for calcium imaging in nonhuman primates: New motor neuroscience and
brain-machine interfaces.
AB - A central goal of neuroscience is to understand how populations of neurons
coordinate and cooperate in order to give rise to perception, cognition, and
action. Nonhuman primates (NHPs) are an attractive model with which to understand
these mechanisms in humans, primarily due to the strong homology of their brains
and the cognitively sophisticated behaviors they can be trained to perform. Using
electrode recordings, the activity of one to a few hundred individual neurons may
be measured electrically, which has enabled many scientific findings and the
development of brain-machine interfaces. Despite these successes,
electrophysiology samples sparsely from neural populations and provides little
information about the genetic identity and spatial micro-organization of recorded
neurons. These limitations have spurred the development of all-optical methods
for neural circuit interrogation. Fluorescent calcium signals serve as a reporter
of neuronal responses, and when combined with post-mortem optical clearing
techniques such as CLARITY, provide dense recordings of neuronal populations,
spatially organized and annotated with genetic and anatomical information. Here,
we advocate that this methodology, which has been of tremendous utility in
smaller animal models, can and should be developed for use with NHPs. We review
here several of the key opportunities and challenges for calcium-based optical
imaging in NHPs. We focus on motor neuroscience and brain-machine interface
design as representative domains of opportunity within the larger field of NHP
neuroscience.
PMID- 27511298
TI - Glycerol metabolism in hypersaline environments.
AB - Glycerol is a key compound for the understanding of the microbiology of
hypersaline environments. At the highest salt concentrations the main or even
sole primary producer is the green unicellular alga Dunaliella, which uses
photosynthetically produced glycerol as osmotic stabilizer and compatible solute.
Glycerol can be expected to be a major carbon source available to the
heterotrophic communities of Archaea and Bacteria in hypersaline ecosystems. Use
of Dunaliella has even been explored for the commercial production of glycerol.
This article reviews our current understanding of glycerol metabolism in
Dunaliella and of the ways glycerol can be degraded by heterotrophic prokaryote
communities under aerobic and under anaerobic conditions. Dunaliella-derived
glycerol may also be the key toward long-term survival of heterotrophic
prokaryotes in fluid inclusions within salt crystals.
PMID- 27511299
TI - Cardiac signal estimation based on the arterial and venous pressure signals of a
hemodialysis machine.
AB - Continuous cardiac monitoring is usually not performed during hemodialysis
treatment, although a majority of patients with kidney failure suffer from
cardiovascular disease. In the present paper, a method is proposed for estimating
a cardiac pressure signal by combining the arterial and the venous pressure
sensor signals of the hemodialysis machine. The estimation is complicated by the
periodic pressure disturbance caused by the peristaltic blood pump, with an
amplitude much larger than that of the cardiac pressure signal. Using different
techniques for combining the arterial and venous pressure signals, the
performance is evaluated and compared to that of an earlier method which made use
of the venous pressure only. The heart rate and the heartbeat occurrence times,
determined from the estimated cardiac pressure signal, are compared to the
corresponding quantities determined from a photoplethysmographic reference
signal. Signals from 9 complete hemodialysis treatments were analyzed. For a
heartbeat amplitude of 0.5 mmHg, the median absolute deviation between estimated
and reference heart rate was 1.3 bpm when using the venous pressure signal only,
but dropped to 0.6 bpm when combining the pressure signals. The results show that
the proposed method offers superior estimation at low heartbeat amplitudes.
Consequently, more patients can be successfully monitored during treatment
without the need of extra sensors. The results are preliminary, and need to be
verified on a separate dataset.
PMID- 27511300
TI - Pinch-off of microfluidic droplets with oscillatory velocity of inner phase flow.
AB - When one liquid is introduced into another immiscible one, it ultimately
fragments due to hydrodynamic instability. In contrast to neck pinch-off without
external actuation, the viscous two-fluid system subjected to an oscillatory flow
demonstrates higher efficiency in breaking fluid threads. However, the underlying
dynamics of this process is less well understood. Here we show that the neck
thinning rate is accelerated by the amplitude of oscillation. By simply
evaluating the momentum transfer from external actuation, we derive a
dimensionless pre-factor to quantify the accelerated pinch-off. Our data ascribes
the acceleration to the non-negligible inner fluid inertia, which neutralizes the
inner phase viscous stress that retards the pinch-off. Moreover, we characterize
an equivalent neck-thinning behavior between an actuated system and its
unactuated counterpart with decreased viscosity ratio. Finally, we demonstrate
that oscillation is capable of modulating satellite droplet formation by shifting
the pinch-off location. Our study would be useful for manipulating fluids at
microscale by external forcing.
PMID- 27511301
TI - Monodisperse Cylindrical Micelles of Controlled Length with a Liquid-Crystalline
Perfluorinated Core by 1D "Self-Seeding".
AB - Precise control over the morphology and dimensions of block copolymer (BCP)
micelles has attracted interest due to the potential of this approach to generate
functional nanostructures. Incorporation of liquid crystalline (LC) block can
provide additional ways to vary micellar morphologies, but the formation of
uniform micelles with controllable dimensions from LC BCPs has not yet been
realized. Herein, we report the preparation of monodisperse cylindrical micelles
with a LC poly(2-(perfluorooctyl)ethyl methacrylate (PFMA) core via a
fragmentation-thermal annealing (F-TA) process, resembling the "self-seeding"
process of crystalline BCP micelles. The average length of the cylinders
increases with annealing temperature, with a narrow length distribution (Lw /Ln
<1.1). We also demonstrate the potential application of the cylinders with LC
cores as a cargo-carrier by the successful incorporation of a hydrophobic
fluorescent dye tagged with a fluorooctyl group.
PMID- 27511302
TI - Geometrical modified nesbit corporoplasty to correct different types of penile
curvature: description of the surgical procedure based on geometrical principles
and long-term results.
AB - We present the use of a modified corporoplasty, based on geometrical principles,
to determine the exact site for the incision in the tunica or plaque and the
exact amount of albuginea for overlaying to correct with extreme precision the
different types of congenital or acquired penile curvature due to Peyronie's
disease. To describe our experience with a new surgical procedure for the
enhancement of penile curvature avoiding any overcorrection or undercorrection.
Between March 2004 and April 2013, a total of 74 patients underwent the
geometrical modified corporoplasty. All patients had congenital curvature until
90 degrees or acquired stable penile curvature 'less' than 60 degrees , that
made sexual intercourse very difficult or impossible, normal erectile function,
absence of hourglass or hinge effect. Preoperative testing included a physical
examination, 3 photographs (frontal, dorsal and lateral) of penis during
erection, a 10 mcg PGE1-induced erection and Doppler ultrasound, administration
of the International Index of Erectile Function (IIEF-15) questionnaire. A follow
up with postoperative evaluation at 12 weeks, 12 and 24 months, included the same
preoperative testing. Satisfaction rates were better assessed with the use of
validated questionnaire such as the International Erectile Dysfunction Inventory
of the Treatment Satisfaction (EDITS). Statistical analysis with Student's t-test
was performed using commercially available, personal computer software. A total
of 25 patients had congenital penile curvature with a mean deviation of 46.8
degrees (range 40-90), another 49 patients had Peyronie's disease with a mean
deviation of 58.4 (range 45-60). No major complications were reported.
Postoperative correction of the curvature was achieved in all patients (100%).
Neither undercorrection nor overcorrection were recorded. No significant relapse
(curvature>15 degrees ) occurred in our patients. Shortening of the penis was
reported by 74% but did not influence the high overall satisfaction of 92%
(patients completely satisfied with their sexual life). The erectile function was
analyzed in both groups, Student's t-test showed a significant improvement in
erectile function, preoperative average IIEF-15 scores were 17.43+/-4.67, whereas
postoperatively it was 22.57+/-4.83 (P=0.001). This geometrical modified Nesbit
corporoplasty is a valid therapy which allows penile straightening. The geometric
principles make the technique reproducible in multicentre studies.
PMID- 27511304
TI - A crystalline anionic complex of scandium nitride endometallofullerene:
experimental observation of single-bonded (Sc3N@Ih-C80(-))2 dimers.
AB - Reduction of scandium nitride clusterfullerene, Sc3N@Ih-C80, by sodium fluorenone
ketyl in the presence of cryptand[2,2,2] allows the crystallization of the
{cryptand[2,2,2](Na(+))}2(Sc3N@Ih-C80(-))2.2.5C6H4Cl2 (1) salt. The Sc3N@Ih-C80(
) radical anions are dimerized to form single-bonded (Sc3N@Ih-C80(-))2 dimers.
PMID- 27511303
TI - Molecular immunology profiles of monkeys following xenografting with the islets
and heart of alpha-1,3-galactosyltransferase knockout pigs.
AB - Effective immunosuppression strategies and genetically modified animals have been
used to prevent hyperacute and acute xenograft rejection; however, the underlying
mechanisms remain unknown. In this study, we evaluated the expression of a
comprehensive set of immune system-related genes (89 genes, including five
housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft
recipients, before and after the xenografting of the islets and heart from single
and double alpha-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks
old). The immunosuppressive regimen included administration of cobra venom
factor, anti-thymocyte globulin, rituximab, and anti-CD154 monoclonal antibodies
to recipients before and after grafting. Islets were xenografted into the portal
vein in type 1 diabetic monkeys, and the heart was xenografted by heterotopic
abdominal heart transplantation. Genes from recipient blood were analyzed using
RT(2) profiler PCR arrays and the web-based RT(2) profiler PCR array software
v.3.5. Recipients treated with immunosuppressive agents without grafting showed
significant downregulation of CCL5, CCR4, CCR6, CD4, CD40LG, CXCR3, FASLG, CXCR3,
FOXP3, GATA3, IGNG, L10, IL23A, TRAF6, MAPK8, MIF, STAT4, TBX21, TLR3, TLR7, and
TYK2 and upregulation of IFNGR1; thus, genes involved in protection against viral
and bacterial infection were downregulated, confirming the risk of infection.
Notably, C3-level control resulted in xenograft failure within 2 days because of
a 7- to 11-fold increase in all xenotransplanted models. Islet grafting using
single GalT-KO pigs resulted in upregulation of CXCL10 and MX1, early
inflammation, and acute rejection-associated signals at 2 days after
xenografting. We observed at least 5-fold upregulation in recipients transplanted
with islets grafts from single (MX1) or double (C3, CCR8, IL6, IL13, IRF6,
CXCL10, and MX1) GalT-KO pigs after 77 days; single GalT-KO incurred early losses
owing to immune attacks. Our results suggest that this novel, simple, non
invasive, and time-efficient procedure (requiring only 1.5 ml blood) for
evaluating graft success, minimizing immune rejection, and blocking infection.
PMID- 27511305
TI - Triboluminescence and crystal structure of the complex [Eu(NO3 )3 (HMPA)3 ]: role
of cleavage planes.
AB - The atomic structure of crystals of the [Eu(NO3 )3 (HMPA)3 ]
[hexamethylphosphotriamide (HMPA)] complex characterized by an intensive
luminescence and triboluminescence was determined using X-ray structural
analysis. Noncentrosymmetric crystals have a monoclinic syngony: a = 16.0686 (3),
b = 11.0853 (2), c = 20.9655 A (4), beta = 93.232 degrees (1), space group P21 ,
Z = 4, rhocalc = 1.560 g/cm3. The crystal structure is represented by individual
S18 N54 EuN12 O12 P3 complexes linked through van der Waals interactions with
clearly expressed cleavage planes. The Eu(III) atom coordination polyhedron
reflected the state of a distorted square antiprism. Structural aspects of the
suggested model, including formation of triboluminescence properties, were
considered and the role of the cleavage planes was discussed.
PMID- 27511306
TI - THE ENIGMA OF ETHIOPIAN SEX RATIOS AT BIRTH.
AB - This study analysed sex ratios at birth (defined as the number of male births per
100 female births) using data on children ever-born from three censuses conducted
in Ethiopia in 1984, 1994 and 2007. The results showed very high values by any
standard, with an average of 108.4 for a sample of some 8.2 million births, with
somewhat lower values in urban areas. Analysis of socioeconomic correlates
revealed that the sex ratio varied very much by household wealth, from about 110
for very poor women to about 102 for wealthier women. The high value of the sex
ratio at birth in Ethiopia could be explained by poverty, used as a proxy for
poor nutritional status. In multivariate analysis, the effects of living in urban
areas and of maternal education were less important than household wealth. Among
the many ethno-linguistic groups, the Nilotic family had higher sex ratios than
other groups. The results were confirmed using data from DHS surveys conducted in
the country, and by the analysis of children still living at time of census.
PMID- 27511307
TI - The effect of counteranions on the molecular structures of phosphanegold(i)
cluster cations formed by polyoxometalate (POM)-mediated clusterization.
AB - The effect of counteranions on the molecular structures of phosphanegold(i)
cluster cations formed by polyoxometalate (POM)-mediated clusterization was
investigated. A novel intercluster compound, [{(AuLCl)2(MU-OH)}2]3[alpha
PMo12O40]2.3EtOH (1-PMo12), was obtained as orange-yellow plate crystals in 12.0%
yield from a 6 : 1 molar ratio reaction of the monomeric phosphanegold(i)
carboxylato complex [Au(RS-pyrrld)(LCl)] (RS-Hpyrrld = RS-2-pyrrolidone-5
carboxylic acid; LCl = tris(4-chlorophenyl)phosphane) in CH2Cl2 with the free
acid-form of Keggin polyoxometalate (POM), H3[alpha-PMo12O40].14H2O. An EtOH/H2O
(5 : 1, v/v) solvent mixture was used. The dimeric cation [{(AuLCl)2(MU
OH)}2](2+) in 1-PMo12 was in a parallel-edge arrangement that was formed by self
assembly through the inter-cationic aurophilic interactions of the MU-OH-bridged
dinuclear phosphanegold(i) cation. The POM anion in 1-PMo12 was successfully
exchanged with a smaller PF6(-) anion by the use of an anion-exchange resin. POM
free, colorless block crystals of [{(AuLCl)3(MU3-O)}2](PF6)2.4CH2Cl2 (2-PF6) were
obtained by vapor diffusion in 14.1% yield. During the synthesis of 2-PF6, a
compound with mixed counteranions (one POM and one PF6(-) anion), i.e.
[{(AuLCl)4(MU4-O)}]2[alpha-PMo12O40]PF6 (3-PMo12PF6), was obtained in 66.4%
yield. Both products were characterized by elemental analysis, TG/DTA, FT-IR,
(31)P{(1)H} NMR, (1)H NMR, and X-ray crystallography. X-ray crystallography
revealed that the countercation in 2-PF6 was the dimeric cation of the MU3-O
bridged tris{phosphanegold(i)} species, whereas that in 3-PMo12PF6 consisted of
an unusual MU4-O-bridged tetragonal-pyramidal tetrakis{phosphanegold(i)} cation.
Therefore, we concluded that the POM anion significantly contributed to the
stabilization of these countercations (parallel-edged arrangement in 1-PMo12 and
MU4-O-bridged tetragonal-pyramid in 3-PMo12PF6). Moreover, the previously
reported yellow crystals of [{(AuLF)2(MU-OH)}2]3[PMo12O40]2.3EtOH (4-PMo12: LF =
tris(4-fluoro phenyl)phosphane) were successfully converted to the POM-free
crystalline OTf(-) salt [{(AuLF)2(MU-OH)}2](OTf)2.0.5Et2O (4-OTf) by the use of
an anion-exchange resin. X-ray crystallography also revealed that the parallel
edge arrangement of the dimeric cation in 4-PMo12 was converted to the crossed
edge arrangement of that in 4-OTf. These results illustrate that the AuOPOM and
hydrogen-bonding (C-HOPOM and O-HOPOM) interactions between the phosphanegold(i)
cluster cation and the Keggin POM anion in the solid state significantly
contribute to the structure, composition, and stability of the phosphane gold(i)
cluster cations in 4-PMo12.
PMID- 27511308
TI - Hoxa-10 and Cyclin D3 Overexpression in the Decidual Reaction in a Superovulation
Protocol in Young Adult C57BL/6J Mice.
AB - Following the performance of a superovulation protocol, multiple nodules were
observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female
mice aged 8.5 +/- 0.6 (mean and standard error of mean) weeks. These lesions
prevented embryo collection, and the uterine decidual reaction was suspected.
Samples of pathological uteri (n = 20) and the normal genital tracts of donors
treated with a similar superovulation protocol (control group, n = 10) were
collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin,
vimentin, progesterone receptor (PR), estrogen receptor alpha (ERalpha), Ki-67,
cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction
to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like
growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a
high degree of structural organization and specifically affected the
antimesometrial region of the endometrium. The abnormal decidual cells were large
polygonal cells that were frequently polyploid or binucleated and strongly
positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index
and higher expression of PR and cyclin D3 in decidual cells in the
antimesometrial aspect of the endometrium, compared to nondecidualized
endometrial stromal cells in the mesometrial aspect of affected uteri, and
compared to endometrial stromal cells in healthy uteri. High expression of cyclin
D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction.
These results suggest that PR overexpression in endometrial stromal cells, likely
due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression,
which may be involved in the pathological mechanisms of the mouse uterine
decidual reaction.
PMID- 27511309
TI - Amyloid-Producing Odontogenic Tumors of the Facial Skin in Three Cats.
AB - Amyloid-producing odontogenic tumors (APOTs) of the facial skin were diagnosed in
3 domestic cats. The neoplasms had the histopathological characteristics of the
odontogenic tumor. The neoplastic cells were present in irregular islands,
strands, and sheets. The peripheral neoplastic cells of the islands and strands
were arranged in a palisading fashion, while the central cells were polyhedral to
stellate and randomly arranged. Multiple spherules of homogeneous eosinophilic
material were closely apposed to the neoplastic epithelial cells. The spherules
stained with Congo red and produced an apple green birefringence under
polarization microscopy, indicative of amyloid. Immunohistochemically, amyloid
materials of the neoplasms reacted with polyclonal antibodies for ameloblastin,
amelogenin, and sheathlin antibodies. Neoplastic epithelial cells also reacted
with antiameloblastin, amelogenin, and sheathlin antibodies, with varied
intensity. The histopathological and immunohistochemical characteristics of
dermal neoplasms of the 3 cats were analogous to those of APOTs reported in the
dog and the cat.
PMID- 27511310
TI - Pathogenesis of Enterococcal Spondylitis Caused by Enterococcus cecorum in
Broiler Chickens.
AB - Enterococcal spondylitis (ES) is a disease of commercial broiler chickens, with a
worldwide distribution. Symmetrical hind limb paralysis typical of ES results
from infection of the free thoracic vertebra (FTV) by pathogenic strains of
Enterococcus cecorum . To determine the pathogenesis of ES, birds with natural
and experimental ES were studied over time. In natural disease, case birds (n =
150) from an affected farm and control birds (n = 100) from an unaffected farm
were evaluated at weeks 1-6. In control birds, intestinal colonization by E.
cecorum began at week 3. In case birds, E. cecorum was detected in intestine and
spleen at week 1, followed by infection of the FTV beginning at week 3. E.
cecorum isolates recovered from intestine, spleen, and FTV of case birds had
matching genotypes, confirming that intestinal colonization with pathogenic
strains precedes bacteremia and infection of the FTV. Clinical intestinal disease
was not required for E. cecorum bacteremia. In 1- to 3-week-old case birds,
pathogenic E. cecorum was observed within osteochondrosis dissecans (OCD) lesions
in the FTV. To determine whether OCD of the FTV was a risk factor for ES, 214
birds were orally infected with E. cecorum, and the FTV was evaluated
histologically at weeks 1-7. Birds without cartilage clefts of OCD in the FTV did
not develop ES; while birds with OCD scores >=3 were susceptible to lesion
development. These findings suggest that intestinal colonization, bacteremia, and
OCD of the FTV in early life are crucial to the pathogenesis of ES.
PMID- 27511311
TI - Wooden Breast Myodegeneration of Pectoralis Major Muscle Over the Growth Period
in Broilers.
AB - Wooden breast (WB) myopathy of broiler chickens is a myodegenerative disease of
an unknown etiology and is macroscopically characterized by a hardened
consistency of the pectoralis major muscle. Our aim was to describe the
development and morphology of WB over the growth period in broilers.
Additionally, the effect of restricted dietary selenium on the occurrence of WB
was examined by allocating the birds in 2 dietary groups: restricted and
conventional level of selenium. The experiment included 240 male broilers that
were euthanized at ages of 10, 18, 24, 35, 38, or 42 days and evaluated for WB
based on abnormal hardness of the pectoralis major muscle. The severity and the
distribution of the lesion and presence of white striping were recorded. The
first WB cases were seen at 18 days; 13/47 birds (28%) were affected and the
majority exhibited a mild focal lesion. In subsequent age groups the WB
prevalence varied between 48% and 73% and the lesion was usually diffuse and
markedly firm. White striping often coexisted with WB. Histological evaluation
performed on 111 cases revealed a significant association of myodegeneration and
lymphocytic vasculitis with WB. Vasculitis and perivascular cell infiltration
were restricted to the veins. Restricted dietary selenium did not affect the
occurrence of WB ( P = .44). Our results indicate that WB starts focally and
spreads to form a diffuse and more severe lesion.
PMID- 27511312
TI - Syncytial Hepatitis of Tilapia ( Oreochromis niloticus L.) is Associated With
Orthomyxovirus-Like Virions in Hepatocytes.
AB - Using transmission electron microscopy (TEM), the presented work expands on the
ultrastructural findings of an earlier report on "syncytial hepatitis," a novel
disease of tilapia (SHT). Briefly, TEM confirmed the presence of an
orthomyxovirus-like virus within the diseased hepatocytes but not within the
endothelium. This was supported by observing extracellular and intracellular
(mostly intraendosomal), 60-100 nm round virions with a trilaminar capsid
containing up to 7 electron-dense aggregates. Other patterns noted included
enveloped or filamentous virions and virion-containing cytoplasmic membrane
folds, suggestive of endocytosis. Patterns atypical for orthymyxovirus included
the formation of syncytia and the presence of virions within the perinuclear
cisternae (suspected to be the Golgi apparatus). The ultrastructural morphology
of SHT-associated virions is similar to that previously reported for tilapia lake
virus (TiLV). A genetic homology was investigated using the available reverse
transcriptase polymerase chain reaction (RT-PCR) probes for TiLV and comparing
clinically sick with clinically normal fish and negative controls. By RT-PCR
analysis, viral nucleic acid was detected only in diseased fish. Taken together,
these findings strongly suggest that a virus is causally associated with SHT,
that this virus shares ultrastructural features with orthomyxoviruses, and it
presents with partial genetic homology with TiLV (190 nucleotides).
PMID- 27511313
TI - Canine Nervous System Lymphoma Subtypes Display Characteristic Neuroanatomical
Patterns.
AB - Primary and secondary nervous system involvement occurs in 4% and 5%-12%,
respectively, of all canine non-Hodgkin lymphomas. The recent new classification
of canine malignant lymphomas, based on the human World Health Organization
classification, has been endorsed with international acceptance. This
histological and immunocytochemical classification provides a unique opportunity
to study the histologic anatomic distribution patterns in the central and
peripheral nervous system of these defined lymphoma subtypes. In this study, we
studied a cohort of 37 dogs with lymphoma, which at necropsy had either primary
(n = 1, 2.7%) or secondary (n = 36; 97.3%) neural involvement. These T- (n = 16;
43.2%) or B-cell (n = 21; 56.8%) lymphomas were further classified into 12
lymphoma subtypes, with predominant subtypes including peripheral T-cell lymphoma
(PTCL) or diffuse large B-cell lymphoma (DLBCL), respectively. This systematic
study identified 6 different anatomically based histologically defined patterns
of lymphoma infiltration in the nervous system of dogs. Different and distinct
combinations of anatomical patterns correlated with specific lymphoma subtypes.
Lymphoma infiltration within the meningeal, perivascular, and periventricular
compartments were characteristic of DLBCL, whereas peripheral nerve involvement
was a frequent feature of PTCL. Similarly cell counts above 64 cells/MUL in
cerebrospinal samples correlated best with marked meningeal and periventricular
lymphoma infiltration histologically. Prospective studies are needed in order to
confirm the hypothesis that these combinations of histological neuroanatomic
patterns reflect targeting of receptors specific for the lymphoma subtypes at
these various sites.
PMID- 27511314
TI - Attitudes toward carrier screening and prenatal diagnosis for recessive
hereditary deafness among the educated population in urban China.
AB - Approximately 80% of hereditary deafness is recessive, in which case most
mutation carriers were unaware of their carrier status. Though parental attitudes
toward genetic testing and prenatal diagnosis are overall positive in those with
deaf children, there is little information about that in the general population.
To this end, we designed a self-completed questionnaire and distributed it in two
colleges in Shanghai, China. A total of 975 completed surveys were returned in
print or online forms. Our results showed that 98.7% of the respondents without
family history of early onset deafness did not know or underestimated their
likelihood to carry a recessive mutation in common deafness genes. After brief
written information was given using GJB2, the most common recessive deafness gene
as the example, 67.7% of the respondents expressed interest in knowing if they
are carriers of GJB2 mutations through genetic testing. In hypothetical
circumstance of carrying a recessive GJB2 mutation, 86.9% would suggest their
partners to also take the test. In case that both were carriers, 88.7% would
consider prenatal diagnosis and 80.7% would consider terminating an affected
pregnancy. On the basis of these results, it was concluded that despite the poor
awareness to the risk of recessive hereditary deafness, the majority of the
educated population in urban China likely hold a positive view toward carrier
screening and prenatal diagnosis of recessive deafness genes. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27511315
TI - A universal explanation of tunneling conductance in exotic superconductors.
AB - A longstanding mystery in understanding cuprate superconductors is the
inconsistency between the experimental data measured by scanning tunneling
spectroscopy (STS) and angle-resolved photoemission spectroscopy (ARPES). In
particular, the gap between prominent side peaks observed in STS is much bigger
than the superconducting gap observed by ARPES measurements. Here, we reconcile
the two experimental techniques by generalising a theory which was previously
applied to zero-dimensional mesoscopic Kondo systems to strongly correlated two
dimensional (2D) exotic superconductors. We show that the side peaks observed in
tunneling conductance measurements in all these materials have a universal
origin: They are formed by coherence-mediated tunneling under bias and do not
directly reflect the underlying density of states (DOS) of the sample. We obtain
theoretical predictions of the tunneling conductance and the density of states of
the sample simultaneously and show that for cuprate and pnictide superconductors,
the extracted sample DOS is consistent with the superconducting gap measured by
ARPES.
PMID- 27511316
TI - Donor liver steatosis: A risk factor for early new-onset diabetes after liver
transplantation.
AB - AIMS/INTRODUCTION: To investigate whether donor liver steatosis increases the
incidence of new-onset diabetes after transplantation (NODAT) in liver transplant
recipients. MATERIALS AND METHODS: We retrospectively analyzed liver transplant
recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December
2014. The final analysis involved 763 patients. The cumulative incidence of NODAT
at 1, 3, 5 and 10 years after liver transplantation was investigated.
Furthermore, according to the findings of donor liver biopsy before
transplantation, patients were divided into steatotic and non-steatotic donor
liver groups, and NODAT incidence was compared between these groups. Multivariate
Cox regression was used to explore the risk factors for NODAT in the patients.
RESULTS: Of the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow
up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an
incidence that exceeded that in the non-steatotic donor liver group (P = 0.001).
The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years
after transplantation was 33, 43, 50 and 56%, respectively. The cumulative
incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group
were significantly higher than those in the non-steatotic donor liver group (P =
0.003). Multivariate Cox regression analyses showed that donor liver steatosis
was an independent risk factor for NODAT among liver transplant recipients, after
other potential risk factors were adjusted for (hazard ratio 1.774, 95%
confidence interval: 1.025-3.073; P = 0.041). CONCLUSIONS: Donor liver steatosis
increases NODAT incidence among liver transplant recipients.
PMID- 27511318
TI - Effective implementation of a patient blood management programme for platelets.
AB - OBJECTIVES: To implement a patient blood management (PBM) programme in platelet
transfusion. AIMS: To improve the appropriate use of blood components, reduce
wastage and generate savings. BACKGROUND: PBM is a multidisciplinary, evidence
based approach to optimising the care of patients who need blood transfusion and
to use blood products appropriately. Strategies for PBM ensure that patients
receive the best possible treatment with the transfusion of components when
indicated, at the same time avoiding or reducing unnecessary transfusions.
Typically, PBM initiatives have addressed the use of red cells. PBM initiatives
in platelets (PBM-P) are an important aspect of Transfusion Medicine. METHODS: We
present data from an initiative for PBM-platelets (PBM-P) comprising a service
improvement programme through the role of a 'platelet co-ordinator' (PBM-Pc) to
optimise the use of platelets in a large complex tertiary care hospital in a
National Health Service (NHS) setting. RESULTS: Analysis at 18 months of the role
showed sustained improvement in compliance with quality standards defined by
British Committee for Standards in Haematology (BCSH) guidelines and significant
financial savings due to improved use and reduced wastage. The appropriate use of
platelets increased by 17, 23 and 18% in the prophylactic, pre-procedure and peri
procedure categories, respectively. Importantly, despite concurrent increases of
patient activity, platelet issues and cost reduced by 21% over the period of
analysis. CONCLUSIONS: Our model has been efficacious in delivering the effective
stewardship of platelets and can be successfully implemented in NHS.
PMID- 27511319
TI - Bullous pemphigoid developed in a patient with prurigo nodularis.
PMID- 27511317
TI - Potential fluid biomarkers for pathological brain changes in Alzheimer's disease:
Implication for the screening of cognitive frailty.
AB - Cognitive frailty (CF) overlaps with early neuropathological alterations
associated with aging-related major neurocognitive disorders, including
Alzheimer's disease (AD). Fluid biomarkers for these pathological brain
alterations allow for early diagnosis in the preclinical stages of AD, and for
objective prognostic assessments in clinical intervention trials. These
biomarkers may also be helpful in the screening of CF. The present study reviewed
the literature and identified systematic reviews of cohort studies and other
authoritative reports. The selection criteria for potentially suitable fluid
biomarkers included: i) Frequent use in studies of fluid-derived markers and ii)
evidence of novel measurement techniques for fluid-derived markers. The present
study focused on studies that assessed these biomarkers in AD, mild cognitive
impairment and non-AD demented subjects. At present, widely used fluid biomarkers
include cerebrospinal fluid (CSF), total tau, phosphorylated tau and amyloid-beta
levels. With the development of novel measurement techniques and improvements in
understanding regarding the mechanisms underlying aging-related major
neurocognitive disorders, numerous novel biomarkers associated with various
aspects of AD neuropathology are being explored. These include specific
measurements of Abeta oligomer or monomer forms, tau proteins in the peripheral
plasma and CSF, and novel markers of synaptic dysfunction, neuronal damage and
apoptosis, neuronal activity alteration, neuroinflammation, blood brain barrier
dysfunction, oxidative stress, metabolites, mitochondrial function and aberrant
lipid metabolism. The proposed panels of fluid biomarkers may be useful in the
early diagnosis of AD, prediction of the progression of AD from preclinical
stages to the dementia stage, and the differentiation of AD from non-AD dementia.
In combination with physical frailty, the present study surmised that these
biomarkers may also be used as biomarkers for CF, thus contribute to discovering
causes and informing interventions for cognitive impairment in individuals with
CF.
PMID- 27511320
TI - The impact of cognitive reserve in the outcome of first-episode psychoses: 2-year
follow-up study.
AB - The concept of cognitive reserve (CR) suggests that the premorbid intelligence
quotient (IQ), years of education and leisure activities provide more efficient
cognitive networks and therefore allow a better management of some conditions
associated to cognitive impairment. Fifty-two DSM-IV diagnosed FEP subjects were
matched with 41 healthy controls by age, gender and parental socio-economic
status. All subjects were assessed clinically, neuropsychologically and
functionally at baseline and after a two-year follow-up. To assess CR at
baseline, three proxies have been integrated: premorbid IQ, years of education
occupation and leisure activities. Higher CR was associated with better
cognitive, functional and clinical outcomes at baseline. The CR proxy was able to
predict working memory, attention, executive functioning, verbal memory and
global composite cognitive score accounting for 48.9%, 19.1%, 16.9%, 10.8% and
14.9% respectively of the variance at two-year follow-up. CR was also
significantly predictive of PANSS negative scale score (12.5%), FAST global score
(13.4%) and GAF (13%) at two-year follow-up. In addition, CR behaved as a
mediator of working memory (B=4.123) and executive function (B=3.298) at baseline
and of working memory (B=5.034) at 2-year follow-up. An additional analysis was
performed, in order to test whether this mediation could be attributed mainly to
the premorbid IQ. We obtained that this measure was not enough by itself to
explain this mediation. CR may contribute to neuropsychological and functional
outcome. Specific programs addressed to improve cognition and functioning
conducted at the early stages of the illness may be helpful in order to prevent
cognitive and functional decline.
PMID- 27511321
TI - It's only a matter of time: the altered role of subsidies in a warming world.
AB - Clockwise from left: an experimental stream reach from the study, highlighting
the fences used to contain fish as the apex predator; a cutthroat trout from the
experiment, the only fish species in the study streams; stomach contents from a
fish, highlighting the major role of the terrestrial subsidy (mealworms) in the
diet. In Focus: Sato, T., El-Sabaawi, R.W., Campbell, K., Ohta, T. & Richardson,
J.S. (2016) A test of the effects of timing of a pulsed resource subsidy on
stream ecosystems. Journal of Animal Ecology, 85, 1136-1146. Cross-ecosystem
subsidies play a critical role in maintaining the structure and functioning of
natural communities, especially if they are asynchronous with resource production
in the recipient ecosystem. Sato et al. () use a large-scale field experiment to
show that changes in the timing of a pulsed terrestrial subsidy can alter stream
dynamics from the individual to the ecosystem level. With increasing evidence
that global warming will alter the timing, magnitude and frequency of
allochthonous inputs, these findings make an important contribution to our
understanding of how such changes will reverberate throughout ecosystems that
depend on subsidies.
PMID- 27511322
TI - Erratum.
PMID- 27511324
TI - Two-Dimensional Skyrmion Lattice Formation in a Nematic Liquid Crystal Consisting
of Highly Bent Banana Molecules.
AB - We synthesized a novel banana-shaped molecule based on a 1,7-naphthalene central
core that exhibits a distinct mesomorphism of the nematic-to-nematic phase
transition. Both the X-ray profile and direct imaging of atomic force microscopy
(AFM) investigations clearly indicates the formation of an anomalous nematic
phase possessing a two-dimensional (2D) tetragonal lattice with a large edge (ca.
59 A) directed perpendicular to the director in the low-temperature nematic
phase. One plausible model is proposed by an analogy of skyrmion lattice in which
two types of cylinders formed from left- and right-handed twist-bend helices
stack into a 2D tetragonal lattice, diminishing the inversion domain wall.
PMID- 27511325
TI - Simvastatin's effects on survival and outcome in traumatic braininjury patients:
a comparative study.
AB - BACKGROUND/AIM: Mortality and morbidity still remain high in patients with
traumatic brain injuries. Understanding the role of new treatments in these
patients is critical. The aim of this study was to determine the effect of
simvastatin on survival and outcome in traumatic brain injury patients. MATERIALS
AND METHODS: Forty-four patients were assigned to receive either simvastatin or a
placebo. The serum interleukin-6 and C-reactive protein levels were measured at
the first 24 h and 48 h after trauma. All data, including the Glasgow Coma Scale
score, survival at discharge, length of intensive care unit stay, and duration of
mechanical ventilation, were collected. The effect of simvastatin on the
collected data was then investigated. RESULTS: The Glasgow Coma Scale level at
discharge was significantly higher in the simvastatin group. The overall
mortality rate, duration of mechanical ventilation, and length of intensive care
unit stay were similar between the 2 groups. The C-reactive protein concentration
48 h after trauma was significantly lower in the simvastatin group, but there was
no significant difference according to the interleukin-6 level 48 h after trauma
between the 2 groups. CONCLUSION: Simvastatin could be suggested as an adjunctive
therapy in traumatic brain injury patients.
PMID- 27511326
TI - CRP, HbA1c, lipid, and biochemical parameters and their relation with maternal
visceral adipose tissue and subcutaneous fat tissue thickness.
AB - BACKGROUND/AIM: The aim of this study was to find whether maternal visceral
tissue (VAT) or subcutaneous fat tissue (SCFT) thicknesses are associated with
CRP, HbA1c, lipid, and biochemical parameters in the first trimester of
pregnancy. MATERIALS AND METHODS: Ninety pregnant women were enrolled. Body mass
index (BMI), VAT, and SCFT were measured. The best cut-off points for grouping
subjects were found to be 4 cm for VAT and 2 cm for SCFT. Venous blood samples
were collected. RESULTS: VAT was higher than 4 cm in all cases with high BMIs.
High CRP and HbA1c were found in 45.5% and 18.2% of cases with VAT over 4 cm,
respectively. CONCLUSION: Besides overall obesity, VAT thickness is the most
important parameter. Decreasing obesity may prevent pathologies caused by
inflammation during pregnancy as well as decrease the risk for future metabolic
and cardiovascular disorders.
PMID- 27511327
TI - The relation between serum cathepsin D level and carotid intima-media thickness
in nondiabetic hypertensive patients.
AB - BACKGROUND/AIM: We aimed to investigate the relation between carotid intima-media
thickness (CIMT) and serum cathepsin D level in hypertensive patients. MATERIALS
AND METHODS: This was a cross-sectional study of 74 hypertensive patients (22
males and 52 females, with a mean age of 51.86 +/- 11.75 years). Serum levels of
cathepsin D were measured with an enzyme-linked immunosorbent assay. CIMT
measurements were taken from 3 different points: right and left common carotid
arteries, bifurcation, and the first 2 cm of the internal carotid artery. Mean
CIMT was calculated by averaging the measurements taken 3 times from each carotid
artery. RESULTS: Mean CIMT value was 0.76 +/- 0.15 mm, and median cathepsin D
level was 190.3 (12.8-2681.3) ng/mL. A marked positive correlation was found
between cathepsin D levels and CIMT (r = 0.331, P = 0.04). In multivariate linear
regression analysis, cathepsin D, albumin levels, and the duration of
hypertension were significant predictors of CIMT (P = 0.017, P = 0.008, and P =
0.043, respectively). CONCLUSIONS: Increased serum cathepsin D level was found to
be associated with CIMT in nondiabetic hypertensive patients.
PMID- 27511328
TI - Genotypes and virulence factors of Candida species isolated from oralcavities of
patients with type 2 diabetes mellitus.
AB - BACKGROUND/AIM: This study compared the genotypes and virulence factors of
Candida species isolated from oral cavities of healthy individuals and patients
with diabetes mellitus (DM). MATERIALS AND METHODS: A total of 142 healthy
individuals and 73 diabetic patients participated in this study. Study
populations were classified into 4 groups as follows: Group I - Healthy, without
caries; Group II - Healthy, with caries; Group III - DM, with caries; Group IV -
DM, without caries. Diabetic patients' blood glucose and hemoglobin A1c
concentrations were determined. Identification of Candida species was performed
with conventional methods. Biofilm production, proteinase, phospholipase, and
esterase were analyzed. The genetic diversity of Candida species was established
using rep-PCR. RESULTS: The most isolated species was Candida albicans. There
were statistical differences in terms of isolated Candida frequency between
healthy subjects and diabetic patients. There was no statistical difference
between the virulence factors of groups. Twelve genotypes were determined. While
there were statistical differences in aerobe biofilm production, proteinase, and
phospholipase activity between genotypes, there were no statistical differences
in anaerobe biofilm production and esterase activity between genotypes.
CONCLUSION: Diabetes has no effect on the activities of virulence factors of
Candida species. Different genotypes of Candida albicans exhibited different
virulence activities.
PMID- 27511329
TI - Host immune responses and peritumoral stromal reactions in different basal cell
carcinoma subtypes: histopathological comparison of basosquamous carcinoma and
high-risk and low-risk basal cell carcinoma subtypes.
AB - BACKGROUND/AIM: The literature does not include sufficient data on the
associations between host immune responses and stromal reactions in different
basal cell carcinoma (BCC) subtypes. The aim of the study was to compare host
immune responses and stromal reactions between basosquamous carcinoma (BSC) and
high-risk (HR) and low-risk (LR) BCC subtypes. MATERIALS AND METHODS: The study
included 35 BSC, 40 HR-BCC, and 40 LR-BCC patients. Age, sex, lesion location,
density of peritumoral/adjacent perivascular inflammation, presence of lymphoid
follicle formation, and stromal reaction type were compared between groups.
RESULTS: In all 3 groups, age, sex distribution, and lesion location were
similar. Overall, 70% of lesions in the LR-BCC group exhibited mild peritumoral
inflammation, whereas in the BSC and HR-BCC groups dense inflammation was
observed in 50% and 57.5% of lesions, respectively (P < 0.001). All lesions
(100%) in the LR-BCC group had fibromyxoid stroma, whereas 61.8% and 80% of
lesions in the BSC and HR-BCC groups, respectively, had desmoplastic stroma (P <
0.001). CONCLUSION: The BSC and HR-BCC groups were similar in terms of host
immune responses and stromal reactions. Furthermore, BSC and HR-BCC were
associated with dense peritumoral inflammation, adjacent perivascular
inflammation, and desmoplastic stroma.
PMID- 27511330
TI - Analysis of the hip fracture records of a central training and research hospital
by selected characteristics.
AB - BACKGROUND/AIM: Despite the importance of hip fractures, very few studies have
assessed their epidemiological characteristics in Turkey. The aim of this study
was to evaluate the frequency and demography of hip fractures from the recent
data of a central training and research hospital. MATERIALS AND METHODS: In this
descriptive study, we identified hip fracture cases between 2009 and 2013. The
age, sex, region, injury pattern, and calendar year for all patients were
evaluated. RESULTS: Among the 687 patients (488 women, 199 men) described in our
clinic's records, 122, 131, 144, 138, and 154 patients applied with hip fractures
from the years 2009 to 2013, respectively. The mean ages of the women and men
were 74.8 and 68.5 years, respectively. There were 220 patients who had femoral
neck fracture (32%), 419 who had intertrochanteric fracture (61%), and 48 who had
subtrochanteric fracture (7%). CONCLUSION: The female geriatric population may
have an increasing and distinct hip fracture risk, mainly in the trochanteric
region. Furthermore, recent studies that show variations in the frequency and
demography of hip fractures highlight the importance of meticulous recording of
patients' information. A nationwide survey of different categories of hospitals
and various geographic regions of Turkey is also needed to inform effective
prevention strategies.
PMID- 27511332
TI - A persistently low HBV DNA level is a predictor of spontaneous HBsAg clearance in
patients with chronic hepatitis B.
AB - BACKGROUND/AIM: The incidence and predictors of spontaneous hepatitis B surface
antigen (HBsAg) seroclearance in patients with chronic hepatitis B virus (HBV)
were evaluated. MATERIALS AND METHODS: A total of 1427 patients with chronic HBV
infection, who were followed between 1994 and 2013, were investigated in this
retrospective study. All data were extracted from patient files. RESULTS:
Spontaneous HBsAg seroclearance occurred in 84 patients during 8798 person-years
of follow-up. The patients were categorized into 3 groups at follow-up based on
HBV DNA features as continuously <100 copies/mL (Group A), 0-10,000 copies/mL
(Group B), and 0 to >10,000 copies/mL (Group C). Alanine aminotransferase
features in the 2 groups were categorized as continuously normal (<40 U/L) and 0
to >40 U/L. Spontaneous HBsAg seroclearance was seen primarily in patients with
Group A HBV DNA features, and continuously low HBV DNA values were the main
predictor of HBsAg seroclearance (P < 0.001). CONCLUSION: These results suggest
that a continuously low viral load is the most important factor affecting
spontaneous HBsAg seroclearance.
PMID- 27511331
TI - Clinical features of infants treated for severe retinopathy of prematurity: 8
yearstudy from a large tertiary neonatal intensive care unit in Turkey.
AB - BACKGROUND/AIM: The aim of this study was to report the gestational age (GA) and
birth weight (BW) distribution of premature babies who needed treatment for
retinopathy of prematurity (ROP) and to assess the timing of the treatment.
MATERIALS AND METHODS: The records of 9008 infants who were screened for ROP were
examined and 556 infants who underwent laser therapy for ROP were reviewed. Sex,
GA, BW, postnatal age, and postmenstrual (PM) age at the time of laser therapy
were recorded. The babies were classified as in-born (Group 1) and out-born
infants (Group 2). RESULTS: The mean GA was 27.3 weeks (range: 22-33 weeks) and
the mean BW was 991.1 g (range: 520-2160 g). Of the treated infants, 7.0% were
born later than 32 weeks and 8.3% were born over 1500 g. The mean postnatal age
was 9.48 weeks (range: 5-22 weeks) and the mean PM age was 36.72 weeks (range: 29
48 weeks) at the time of treatment. Mean BWs and GAs were significantly higher
and the mean postnatal age at the time of laser therapy was significantly earlier
in Group 2. CONCLUSION: Infants with severe ROP had a wider range of BWs and GAs
compared to those from developed countries and earlier treatment was needed for
out-born infants.
PMID- 27511333
TI - Evaluation of intraabdominal hypertension and genitofemoral nerve motor
conduction.
AB - BACKGROUND/AIM: The aim of this study was to electrophysiologically evaluate the
effect of increased intraabdominal pressure (IAP) on genitofemoral nerve (GFN)
motor conduction. MATERIALS AND METHODS: Seven Wistar albino rats were included.
After anesthetization, latency and duration of GFN conduction was recorded with a
needle-probe at rest. IAP was increased to 15 mmHg by insufflating atmospheric
air with a percutaneous intraperitoneal needle. At 30 min of IAP, GFN motor
conduction was recorded. Abdominal pressure was then increased to 20 mmHg. At 60
min, GFN motor conduction was recorded again. The consecutive recordings of
latency and duration of GFN conduction (rest, 30 min, 60 min) were evaluated
statistically. RESULTS: There was a significant difference between latencies at
rest (1.90 +/- 0.22 ms), at 30 min (2.3 +/- 0.36 ms), and at 60 min (2.74 +/-
0.57 ms) (Friedman test, P = 0.001). The latency was significantly increased at
60 min compared to rest (post hoc Tukey test, P = 0.003). No similar difference
was detected between the recordings at 30 and 60 min. The duration of GFN motor
conduction showed no difference between consecutive recordings (P = 0.067).
CONCLUSION: Both increased and prolonged IAP causes prolonged latency of GFN
conduction, probably due to a compression effect on GFN. Neuropraxial
consequences of increased IAP are thought to be related to the compression effect
of peripheral nerves.
PMID- 27511334
TI - Mucormycosis: a 10-year experience at a tertiary care center in Turkey.
AB - BACKGROUND/AIM: Mucormycosis is a rare invasive fungal infection most commonly
encountered in the immunocompromised host. We analyzed 51 adult patients treated
for mucormycosis between 2003 and 2013 and recorded at a tertiary university
hospital in Turkey. MATERIALS AND METHODS: We examined the following data for all
patients: age, sex, predisposing disease, symptoms, treatment, surgical
procedure, concomitant infections, intensive care requirement, and outcomes.
RESULTS: During the study period 51 cases of mucormycosis were documented; 54.9%
of the patients were female. The mean age was 44.2 +/- 18.2 years. Rhinocerebral
presentation was reported in 94.1% of patients. Almost all patients (88.2%) had
at least one risk factor. The common predisposing factors were hematologic
malignancies (52.9%), diabetes mellitus (25.5%), and solid malignancies (5.8%).
The most common initial symptoms were fever, cellulitis, and facial pain. The
primary medication used was liposomal amphotericin B or conventional amphotericin
B. Surgery was performed in 94.1% of patients. Mortality was 52.9%. CONCLUSION:
Our study revealed that mucormycosis continues to be a mortal disease in about
half of the cases. Our findings indicate that treatment with L-AMB is associated
with a favorable response. Also, in the case of facial pain, the low mortality
rate may indicate the importance of early diagnosis.
PMID- 27511335
TI - Minor salivary gland evaluation: Sjogren's syndrome.
AB - BACKGROUND/AIM: We aimed to analyze the value of 3 serial sections, spaced 200
um apart, for quantification of lymphocyte and plasma cell foci in minor salivary
gland biopsy (MSGB). MATERIALS AND METHODS: Labial MSGBs from 69 patients with
Sjogren's syndrome (SS) and scleroderma were used for this study. Each sample was
prepared as 3 serial sections spaced 200 um apart. Lymphocytic and plasma cell
focus score (LFS, PFS) were determined for each section, and the diagnostic
results were compared to those obtained from a single section. RESULTS: For 22 of
the 69 patients, all 3 sections were scored at <1 and interpreted as inconclusive
for the presence of SS. For 20 cases, all 3 sections were scored at >=1 and
interpreted as diagnostic for SS. In the remaining 27 cases, the score was found
to vary between sections. Plasma cell foci were observed in 11 cases, with 5
cases exhibiting a PFS of >=1. Of those 5 cases, 4 also had a LFS of >=1.
CONCLUSION: Assessment of 3 serial sections in MSGB has the potential to improve
accuracy of SS diagnosis by detecting specific features that may not have been
detected in a single section. We concluded that data about the PFS require
further evaluation.
PMID- 27511336
TI - Distribution of hepatitis C virus genotypes among intravenous drug users in the
Cukurova region of Turkey.
AB - BACKGROUND/AIM: The most common hepatitis C virus (HCV) genotype in Turkey is
genotype 1. However, there has not been a study about the distribution of HCV
genotypes among intravenous drug users (IVDUs) in the Cukurova region of Turkey.
This study was planned to understand if there is a difference between IVDUs and
the normal population. MATERIALS AND METHODS: Between May 2010 and May 2014, anti
HCV positive IVDUs who applied to the 6 hospitals in the Cukurova region of
Turkey were included in this study. Their HCV genotypes were studied. RESULTS:
Ninety-seven anti-HCV positive IVDUs were screened in terms of HCV RNA and
genotype. Ten were excluded from the study because their HCV RNA results were
negative. Fifty-one of the 87 patients (58.6%) had genotype 3. Genotype 2 was
detected in 26 (29.9%) and genotype 1 was detected in 10 (11.5%) patients.
CONCLUSION: HCV genotypes seem to be different between the normal population and
IVDUs according to studies worldwide. Among IVDUs, we detected a dominance of
genotype 3 and genotype 2, which is apparently different from the normal
population. The reason for this difference can be simply explained by infection
through shared needles. However, there may still be a different immunological
response in IVDUs, the investigation of which may lead to further studies.
PMID- 27511337
TI - Seasonal vitamin D status and endothelial function in healthcare workers.
AB - BACKGROUND/AIM: Healthcare workers have long working hours indoors and are at
risk of vitamin D deficiency. The aim of this study was to determine seasonal
vitamin D status and its relationship with early atherosclerotic markers,
endothelial function, and carotid intima-media thickness (CIMT) in healthcare
workers of Marmara University Hospital, Istanbul. MATERIALS AND METHODS: One
hundred and ninety healthy volunteer healthcare workers and 66 nonmedical
volunteers of Marmara University Hospital were included in the study and 25
hydroxyvitamin D (25(OH)D), calcium, intact parathyroid hormone (PTH),
endothelial function, and CIMT were measured twice during winter and summer
seasons. RESULTS: Mean vitamin D levels were 20 ng/mL in summer and 16.4 ng/mL in
winter. Out of the healthcare workers, 48.9% were vitamin D deficient at the end
of summer and 71.5% in winter. Flow-mediated dilation (FMD) values were similar
in both groups in both seasons; however, FMD values of 64 healthcare workers in
summer were significantly higher than in winter. Serum 25(OH)D was positively
associated with FMD (r = 0.1797, P = 0.0441) and negatively correlated with serum
PTH (r = -0.2459, P < 0.0001). A negative correlation between FMD and serum PTH
(r = -0.1757, P = 0.0473) was observed. CONCLUSION: Vitamin D levels of
healthcare workers are very low, even in summer time. Healthcare workers must be
considered a group at major risk for vitamin D deficiency.
PMID- 27511338
TI - Recurrent dilatation in resistant benign esophageal strictures: timing is
significant.
AB - BACKGROUND/AIM: Benign esophageal strictures are frequently encountered
pathologies occurring due to various reasons. Repeated dilatations may be needed,
particularly in resistant strictures. This study aimed to evaluate patients who
underwent repeated dilatations in our clinic due to resistant esophageal
strictures. MATERIALS AND METHODS: Sixteen patients who underwent multiple
dilatations in our clinic with the diagnosis of resistant benign esophageal
stricture between 2007 and 2014 were studied for age, sex, etiology, symptoms,
complications, number of dilatations, and intervals between dilatations. Under
general anesthesia, all patients underwent dilatation with Savary-Gilliard bougie
dilators with the help of rigid esophagoscopy. RESULTS: In 10 of the patients,
stenosis was cervical, and in others it was in the thoracic esophagus. The mean
dilatation performance was 4.4 (range: 3-12). In 9 patients, dilatations were
performed when the patients presented with the complaint of dysphagia. Following
the initial dilatation performed for dysphagia, 7 patients underwent endoscopy
and dilatation 3-5 times with 1-week intervals without waiting for the
development of dysphagia symptoms. These patients developed no complications, and
no stenting was needed. In 5 patients, restenosis developed despite multiple
dilatations, and esophageal stent placement was performed. CONCLUSION:
Dilatations performed at frequent intervals without waiting for the symptoms of
dysphagia can contribute to safer and more effective results in resistant benign
esophageal strictures.
PMID- 27511339
TI - Diagnostic accuracy of noninvasive end-tidal carbon dioxide measurement in
emergency department patients with suspected pulmonary embolism84-90.
AB - BACKGROUND/AIM: Pulmonary embolism (PE) is a frequent health problem representing
a diagnostic challenge with high mortality and morbidity rates. The aim of this
study was to investigate the value of end-tidal carbon dioxide (ETCO2) and
alveolar dead space fraction (ADSF) in the diagnosis of PE. MATERIALS AND
METHODS: ETCO2 levels of patients with suspected PE were measured with a
noninvasive mainstream sensor. ADSF of patients was calculated and PaCO2 levels
were also obtained. ROC curve analysis was used to determine diagnostic values of
ETCO2 and ADSF for PE. RESULTS: The study included 159 patients. The mean values
for ETCO2 and ADSF were 16.27 (95% CI, 14.52-18.03) and 0.48 (95% CI, 0.43-0.539)
in the PE group and 21.57 (95% CI, 20.52-22.639) and 0.35 (95% CI, 0.32-0.38) in
the non-PE group. The area under the curve (AUC) and the cut-off point for ETCO2
were found as 0.751 and <=19, with 83.8% sensitivity and 61.5% specificity. AUC
and cut-off point for ADSF were found as 0.738 and >0.443, with 67.57%
sensitivity and 73.77% specificity. CONCLUSION: The diagnostic value of
calculated ADSF and noninvasive bedside ETCO2 for PE was found to be low.
PMID- 27511340
TI - An experimental comparative study on classic tube thoracostomy and thoracostomy
with a newly designed thorax drainage catheter.
AB - BACKGROUND/AIM: The collection of fluids, blood, pus, or air in the pleural
cavity is a pathological condition requiring pleural drainage. A newly designed
thorax drainage catheter in the prototype phase was used in this experimental
study to test its efficacy. MATERIALS AND METHODS: A hemopneumothorax was first
caused by a penetrating injury on the frontal axis of the sixth intercostal space
on the right hemithorax with a scalpel on 6 female Sus domesticus swine subjects.
After resting for 5 min, a tube or catheter was inserted. The same procedure with
a tube thoracostomy or thorax drainage catheter was repeated on the left
hemithorax. The time periods were recorded. After all procedures were completed,
the thoracic organs were assessed for iatrogenic injuries. RESULTS: In terms of
time elapsed for procedure, statistically significant differences between the
tube thoracostomy and thorax drainage catheter applications were identified (P <
0.05). Additional iatrogenic injuries were nonexistent for both groups. During
the thorax drainage catheter application, a surgical set or the use of sutures
was not required. CONCLUSION: This study showed promising results regarding the
efficacy of the thorax drainage catheter for convenient use in prehospital and
hospital settings by physicians with little experience with tube thoracostomy.
PMID- 27511341
TI - Frequency of twelve carcinogenic human papilloma virus types among women from the
South Backa region, Vojvodina, Serbia.
AB - BACKGROUND/AIM: The aim of this study was to determine the presence and age
distribution of different oncogenic human papilloma virus (HPV) types in women in
the South Backa region and its relationship to Pap results. MATERIALS AND
METHODS: In a group of 1087 women with normal and abnormal cytology, the
commercial HR HPV Real-TM kit (Sacace Biotechnologies, Italy) was used. RESULTS:
Overall, 50.5% of the women were HPV positive. The presence of HPV types 18, 31,
51, and 58 was significantly influenced by age, while the presence of HPV types
16 and 45 was significantly influenced by cervical cytology. Results of the LSD
test show a wide spectrum of high risk HPV among women with normal cytology and
women with a low grade cervical lesion rate (atypical squamous cell of
undetermined significance (ASCUS) and low grade squamous intraepithelial lesions
(LSIL). The most prevalent HPV types found were 16, 31, 51, 18, and 52. In the
HSIL group the most prevalent HPV types were 16 and 45. CONCLUSION: The reported
results provide new data on the circulation of oncogenic HPV genotypes and
frequency of multiple infections among women in Vojvodina and suggest that a
prophylactic vaccine against HPV 16 and 18 has the potential to prevent
approximately half of the high-grade lesions.
PMID- 27511342
TI - The effect of transtheoretical model-based individual counseling, training, and a
6-month follow-up on smoking cessation in adult women: a randomized controlled
trial.
AB - BACKGROUND/AIM: This study was conducted to determine the effect of
transtheoretical model (TTM)-based individual counseling, training, and a 6-month
follow-up on smoking cessation in adult women. MATERIALS AND METHODS: We carried
out this randomized controlled trial in Konya, Turkey. Female subjects were
randomly assigned into groups in a 1:1 ratio using block randomization, block
size 3 * 3, divided by stages (precontemplation, contemplation, and preparation)
and age (20-29, 30-39, and 40-49 years). The study was completed with 77 women
(an intervention group containing 38 participants and a control group of 39
participants). The intervention group was interviewed 5 times (baseline and 1,
1.5, 2, and 6 months). Counseling and training were given to the intervention
group at the first 3 interviews. The TTM scales were assessed for both groups at
baseline and at 2 and 6 months. RESULTS: In the 6-month follow-up, the rate of
smoking cessation and the rate of progress were higher in the intervention group
than in the control group. All the TTM variables had differences except the
cognitive processes in the intervention group over time. Analysis of variance
related to time * groups indicated that all variables had significantly changed
except the cognitive processes and the pros of change. CONCLUSION: Results
suggest that the TTM may be useful in understanding the stages individuals are at
and in deciding on the appropriate treatment for smoking cessation.
PMID- 27511343
TI - The utility of EBUS-TBNA in mediastinal or hilar lymph node evaluation in
extrapulmonary malignancy.
AB - BACKGROUND/AIM: The aim of this study was to determine the diagnostic performance
of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)
in the diagnosis of mediastinal and hilar lymph nodes (LNs) in patients with
known extrapulmonary malignancy. MATERIALS AND METHODS: Between March 2011 and
August 2013, 378 EBUS-TBNA procedures were performed. Sixty-three (16.6%) of
these were performed on known extrapulmonary malignancy patients. RESULTS: There
were 28 male and 35 female patients, with median ages of 65 years (min-max: 53
87) and 57 years (min-max: 39-76), respectively. From the 63 cases, 138 lymph
nodes (LNs) were sampled with EBUS-TBNA (median: 2 LNs/patient; min-max: 1-4).
Results of EBUS-TBNA revealed malignancy in 18 (28.5%) and nonmalignancy in 45
(71.5%). In the nonmalignant group, there were false negatives in 5 (7.9%),
anthracosis in 13 (20.6%), reactive adenitis in 16 (25.3%), sarcoidosis in 7
(11.1%), and tuberculosis in 2 (3.1%), and 2 were not evaluated (lost to follow
up) (3.1%). The diagnostic sensitivity, accuracy, and negative predictive value
of EBUS-TBNA per patient were 78.2%, 91.8%, and 88.3%, respectively. CONCLUSION:
EBUS-TBNA is a safe, minimally invasive, and effective method and can be
considered as the initial test for the histopathological diagnosis of mediastinal
and hilar lymphadenopathy in patients with extrapulmonary malignancy.
PMID- 27511344
TI - Liporotein-associated phospholipase-A2 can be a diagnostic marker inthe early
stage diagnosis of acute mesenteric ischemia.
AB - BACKGROUND/AIM: The purpose of this experimental study was to investigate the
role of lipoprotein-associated phospholipase-A2 (Lp-PLA2) in the diagnosis of
acute mesenteric ischemia (AMI) in the early stage. MATERIALS AND METHODS: Twenty
seven New Zealand rabbits were randomly divided into 3 groups in this study.
Blood specimens were obtained from the groups at hours 0, 1, 3, and 6. Using the
blood samples drawn from all groups, Lp-PLA2 and C-reactive protein (CRP)
parameters were investigated. RESULTS: There was a significant rise in the levels
of both Lp-PLA2 and CRP starting at hour 1 (P < 0.05) (hour 1; Lp-PLA2, P =
0.003) in the ischemia group. In the sham group, the levels of Lp-PLA2 and CRP
started to rise at hour 3 (P < 0.05) (hour 3; Lp-PLA2, P = 0.011). At hour 6 of
ischemia, the area under the ROC curve was 100%, and the cut-off value of 63.91
ng/mL revealed a sensitivity of 88% and a specificity of 100% for Lp-PLA2.
CONCLUSION: These findings showed the role of serum Lp-PLA2 and CRP levels in the
early diagnosis of AMI. Thus, further studies are needed to describe the role of
Lp-PLA2 in the early diagnosis of AMI.
PMID- 27511345
TI - Investigation of ischemia-modified albumin levels and some atherosclerosis
related serum parameters in patients with diabetic foot.
AB - BACKGROUND/AIM: To investigate serum ischemia-modified albumin (IMA), oxidized
low-density lipoprotein (ox-LDL) levels, and paraoxonase 1 (PON1) activity in
patients with diabetic foot. MATERIALS AND METHODS: Thirty patients with diabetes
mellitus (DM), 30 patients with diabetic foot (29 and 27 of these patients had
type 2 DM, respectively), and 30 healthy volunteers as the control group were
included in the study. The patients with diabetic foot were divided into 2
groups, as those who had or had not undergone lower extremity amputation. Serum
PON1 activity, ox-LDL, and IMA levels were measured. RESULTS: Serum PON1 activity
was lower (P < 0.05) and ox-LDL levels were higher (P < 0.05) in the diabetic
foot group than in the control and diabetes groups. Albumin-adjusted IMA values
were higher (P < 0.001) in the diabetic foot group compared to the diabetes
group. The postamputation levels of IMA were decreased compared to the
preamputation condition (P < 0.05). CONCLUSION: The low activity of PON1 and the
high levels of ox-LDL and IMA may play an important role in the pathogenesis of
diabetic foot. The use of these parameters in the follow-up of patients with DM
may prevent the development of diabetic foot. In order to reach a definitive
judgment, further studies with a larger number of subjects are necessary.
PMID- 27511346
TI - Impact of antimicrobial drug restrictions on doctors' behaviors.
AB - BACKGROUND/AIM: Broad-spectrum antibiotics have become available for use only
with the approval of infectious disease specialists (IDSs) since 2003 in Turkey.
This study aimed to analyze the tendencies of doctors who are not disease
specialists (non-IDSs) towards the restriction of antibiotics. MATERIALS AND
METHODS: A questionnaire form was prepared, which included a total of 22
questions about the impact of antibiotic restriction (AR) policy, the role of
IDSs in the restriction, and the perception of this change in antibiotic
consumption. The questionnaire was completed by each participating physician.
RESULTS: A total of 1906 specialists from 20 cities in Turkey participated in the
study. Of those who participated, 1271 (67.5%) had <=5 years of occupational
experience (junior specialists = JSs) and 942 (49.4%) of them were physicians.
Specialists having >5 years of occupational experience in their branch expressed
that they followed the antibiotic guidelines more strictly than the JSs (P <
0.05) and 755 of physicians (88%) and 720 of surgeons (84.6%) thought that the AR
policy was necessary and useful (P < 0.05). CONCLUSION: This study indicated that
the AR policy was supported by most of the specialists. Physicians supported this
restriction policy more so than surgeons did.
PMID- 27511347
TI - Ophthalmic pathologies in female subjects with bilateralcongenital sensorineural
hearing loss.
AB - BACKGROUND/AIM: The high prevalence of ophthalmologic pathologies in hearing
disabled subjects necessitates early screening of other sensory deficits,
especially visual function. The aim of this study is to determine the frequency
and clinical characteristics of ophthalmic pathologies in patients with
congenital bilateral sensorineural hearing loss (SNHL). MATERIALS AND METHODS:
This descriptive study is a prospective analysis of 78 young female SNHL subjects
who were examined at a tertiary care university hospital with a detailed
ophthalmic examination, including electroretinography (ERG) and visual field
tests as needed. RESULTS: The mean age was 19.00 +/- 1.69 years (range: 15 to 24
years). A total of 39 cases (50%) had at least one ocular pathology. Refractive
errors were the leading problem, found in 35 patients (44.9%). Anterior segment
examination revealed heterochromia iridis or Waardenburg syndrome in 2 cases
(2.56%). Dilated fundus examination revealed retinal pathologies in 15 cases
(19.23%), including retinitis pigmentosa or Usher's syndrome in 8 cases (10.25%).
Most of the Usher's syndrome cases (87.5%) had consanguinity. CONCLUSION:
Screening for congenital SNHL in the early years of life and routine yearly
follow-ups are essential for maximizing the rehabilitation of this disabled
group. The high rate of visually debilitating syndromic ocular pathologies
associated with high frequency of consanguinity doubles the importance.
PMID- 27511348
TI - Effects of immunosuppressive drugs on oral mucosa in patients with Behcet's
disease: cytomorphological and cytopathological assessment.
AB - BACKGROUND/AIM: The aim of this study was to investigate cytomorphological and
cytopathological changes in oral exfoliated smears collected from
immunosuppressed patients with Behcet's disease (BD) using stereological methods.
MATERIALS AND METHODS: For cytomorphometric analysis, mucosal cell smears were
obtained from the buccal mucosa and the floor of the mouths of BD patients
treated with immunosuppressive drugs and from healthy volunteers. All mucosal
smears from the patients and the healthy volunteers were stained using the
Papanicolaou method and examined cytopathologically under light microscopy and
cytomorphologically via the stereological nucleator method. RESULTS: The
cytomorphological analysis revealed 3 types of mucosal cells, with numbers of
particularly pink cells lower in the aphthous areas of the patients with BD
compared to the healthy controls (P < 0.05). The nuclear volumes (NVs) and
cytoplasmic volume (CVs) were significantly higher in the BD patients (P < 0.05),
but the NV/CV ratio was higher only in the drug-use patient groups (P > 0.05).
There was lower apoptotic activity in the nondrug-use patients with BD and in the
immunosuppressive-taking BD patients. CONCLUSION: The findings suggest that
quantifiably morphological and morphometric changes in oral mucosa can be
detected by stereological techniques. Changes in these parameters may indicate
malignant transformation in the oral mucosa.
PMID- 27511349
TI - Cost-effectiveness analysis of pemetrexed and gemcitabine treatment for advanced
nonsmall cell lung cancer in Turkey.
AB - BACKGROUND/AIM: The purpose of the study is to determine the cost-effectiveness
of the chemotherapy medications that contain gemcitabine and pemetrexed, which
are used in the treatment of advanced nonsmall cell lung cancer (NSCLC).
MATERIALS AND METHODS: The study evaluated the effectiveness and cost of platinum
based pemetrexed and gemcitabine treatments as the first-line treatment of
advanced NSCLC with the use of the Markov model, and from the perspective of the
Social Security Institution. NSCLC costs calculated on the basis of experts'
opinions and the effectiveness values calculated by administering the EQ-5D
questionnaire to the patients were analyzed. All direct medical costs were
included in the model. RESULTS: While the life-long cost of gemcitabine/cisplatin
treatment was determined to be 10,347.45 Turkish lira per patient, it was
determined as 17,783.34 for pemetrexed/cisplatin treatment. The incremental cost
of pemetrexed/cisplatin treatment is 220,754 per quality-adjusted life year.
CONCLUSION: Although there is no official threshold value in Turkey, due to the
fact that the incremental cost effectiveness ratio exceeds the threshold value
calculated on the basis of GDP per capita, it is understood that
pemetrexed/cisplatin is not cost-effective in the first-line treatment of
advanced NSCLC.
PMID- 27511350
TI - Significance of using a nonlinear analysis technique, the Lyapunov exponent, on
the understanding of the dynamics of the cardiorespiratory system in rats.
AB - BACKGROUND/AIM: Pneumocardiography (PNCG) is the recording method of cardiac
induced tracheal air flow and pressure pulsations in the respiratory airways.
PNCG signals reflect both the lung and heart actions and could be accurately
recorded in spontaneously breathing anesthetized rats. Nonlinear analysis
methods, including the Lyapunov exponent, can be used to explain the biological
dynamics of systems such as the cardiorespiratory system. MATERIALS AND METHODS:
In this study, we recorded tracheal air flow signals, including PNCG signals,
from 3 representative anesthetized rats and analyzed the nonlinear behavior of
these complex signals using Lyapunov exponents. RESULTS: Lyapunov exponents may
also be used to determine the normal and pathological structure of biological
systems. If the signals have at least one positive Lyapunov exponent, the signals
reflect chaotic activity, as seen in PNCG signals in rats; the largest Lyapunov
exponents of the signals of the healthy rats were greater than zero in this
study. CONCLUSION: A method was proposed to determine the diagnostic and
prognostic values of the cardiorespiratory system of rats using the arrangement
of the PNCG and Lyapunov exponents, which may be monitored as vitality
indicators.
PMID- 27511351
TI - Effects and mechanisms of curcumin on the hemodynamic variablesof isolated
perfused rat hearts.
AB - BACKGROUND/AIM: There is no information on the dose-response relationship of
curcumin on the hemodynamic variables of the heart at the organ level in isolated
perfused rat hearts. We aimed to investigate the effects and mechanisms of
curcumin on the hemodynamic variables of isolated perfused rat hearts. MATERIALS
AND METHODS: Rats were randomly divided into 9 groups. The isolated rat heart was
retrogradely perfused with modified Krebs-Henseleit solution. After the
stabilization period, each group was administered one of the following treatments
for 25 min: saline, dimethyl sulfoxide, and curcumin (0.2 uM, 1 uM, and 5 uM);
atropine (1 uM); atropine (1 uM) + curcumin (1 uM); L-NAME (100 uM); or L-NAME
(100 uM) + curcumin (1 uM). Hemodynamic variables of the heart were measured.
RESULTS: Curcumin at dose of 1 uM decreased the heart rate (from 271 +/- 11.1 to
200.4 +/- 14.3 beats/min, P = 0.011) but increased end-diastolic pressure (from
7.0 +/- 0.4 to 54.6 +/- 7.9 mmHg, P = 0.0008). A dose of 5 uM curcumin caused a
decrease in the developed pressure (from 87.58 +/- 9.0 to 65.40 +/- 7.0 mmHg, P =
0.047) but an increase in the end-diastolic pressure (from 6.8 +/- 0.6 to 48.9 +/
7.7 mmHg, P = 0.005). Atropine (1 uM) reversed the effects of curcumin on the
heart. CONCLUSION: Our results suggest that curcumin produces dose-dependent
negative chronotropic and inotropic effects in isolated perfused rat hearts.
PMID- 27511352
TI - Intrabone marrow injection enhances placental mesenchymal stem cellmediated
support of hematopoiesis in mice.
AB - BACKGROUND/AIM: In order to determine the synergistic effects of human placental
mesenchymal stem cells (PMSCs) on hematopoiesis in vivo, we compared the
intrabone marrow injection (IBMI) with the conventional intravenous injection
(IVI). MATERIALS AND METHODS: C57BL/6 recipient mice conditioned with lethal
doses of irradiation were transplanted with bone marrow mononuclear cells (MNCs)
and bone marrow-derived mesenchymal stem cells (BMSCs) from BALB/c mice by IBMI
or IVI. NOD/SCID recipient mice conditioned with sublethal doses of irradiation
were transplanted with human umbilical cord blood MNCs (UCB-MNCs) and PMSCs by
IBMI or IVI. RESULTS: The number of hematopoietic cells was significantly higher
in mice transplanted with BMSCs by IBMI than in those transplanted by IVI in a
murine transplantation model (BALB/c->C57BL/6). Moreover, the percentage of human
hematopoietic cells in the tibiae of the NOD/SCID mice that were transplanted
with PMSCs plus UCB-MNCs was higher than that in mice transplanted with UCB-MNCs
alone. In addition, in mice that were transplanted with PMSCs, PMSCs injected by
IBMI were more efficient than those injected by IVI. CONCLUSION: Our results not
only elucidated the role of PMSCs in promoting hematopoiesis, but also revealed
the therapeutic potential of the combination of PMSCs and IBMI in
transplantation.
PMID- 27511353
TI - The effect of proanthocyanidin on formaldehyde-induced toxicity in rat testes.
AB - BACKGROUND/AIM: This study investigated the effect of proanthocyanidin (PA)
against formaldehyde (FA)-induced lipid peroxidation damage and morphological
changes in rat testes. MATERIALS AND METHODS: Twenty-one Wistar albino rats were
randomized into 3 groups: control, FA, and FA + PA groups. Plasma and tissue
malondialdehyde (MDA) and total sialic acid (TSA) levels were measured. Testes
tissues were observed by light and electron microscopy. RESULTS: TSA (plasma and
tissue) levels decreased and MDA (plasma) significantly increased (P < 0.05) in
rats treated with FA compared to the controls. Tissue MDA levels were not
significantly different. Several necrotic changes were observed in testes tissues
by light and electron microscopy. Disordering in epithelia of seminiferous
tubules, vacuolization between germinal epithelium cells, and separated basement
membranes were observed by light microscope. Immunopositivity in Leydig cells
decreased in the FA group (P < 0.05). In the FA + PA group there were more immune
Leydig cells reacting immune-positively than in the FA group (P < 0.05).
Ultrastructurally, FA also caused disorganization and loss of mitochondrial
cristae, and dilatation in endoplasmic reticulum in testes. CONCLUSION: The
results suggest that PA has a protective effect on FA toxicity in testes.
PMID- 27511354
TI - Apitherapy products enhance the recovery of CCL4-induced hepatic damages in rats.
AB - BACKGROUND/AIM: Our objective was to identify the antioxidant properties of
honeybee products from Turkey, chestnut honey, pollen, propolis, and royal jelly,
and their hepatoprotective activity against CCl4-induced hepatic damage in rats.
MATERIALS AND METHODS: Animals were fed with honeybee products for 7 days
following CCl4 injection. Development of liver damage and oxidative stress were
monitored by measuring the activities of the enzymes alanine transaminase,
aspartate transaminase, malondialdehyde, superoxide dismutase, and catalase.
Antioxidant capacities of the bee products were identified using FRAP and DPPH
assays, as well as by measuring total phenolic and flavonoid contents. RESULTS:
The antioxidant activities of the honeybee products were highest in propolis,
followed, in order, by pollen, honey, and royal jelly. Despite their different
levels of antioxidant capacity, their roles in the prevention of liver damage
induced by CCl4 were very similar, which can be explained through their
bioavailability to the treated animals. CONCLUSIONS: Our results suggest that
honey, propolis, pollen, and royal jelly significantly enhanced the healing of
CCl4-induced liver damage, partially due to their antioxidant properties and
bioavailability.
PMID- 27511355
TI - Comparison of a real-time polymerase chain reaction-based system and Erlich-Ziehl
Neelsen method with culture in the identification of Mycobacterium tuberculosis.
AB - BASCKGROUND/AIM: Mycobacterium tuberculosis is still a major health problem
throughout the world, especially in developing countries. Disease control heavily
depends on the establishment of early diagnosis. The aim of this study is to
compare the efficacy of culture, GeneXpert MTB/RIF device, and Erlich-Ziehl
Neelsen direct microscopic method. MATERIALS AND METHODS: A total of 927 samples
(243 respiratory and 684 nonrespiratory), which were sent to Ondokuz Mayis
University Medical Faculty Tuberculosis Laboratory on suspicion of M.
tuberculosis, were included in the study. RESULTS: When compared to standard
culture, sensitivity, specificity, and positive and negative predictive values of
the GeneXpert system for respiratory samples were 100%, 98.7%, 87%, and 100%,
respectively; these values for nonrespiratory samples were 71%, 98.6%, 71%, and
98.6%, respectively. CONCLUSION: New, reliable, rapid, and easy-to-use methods
that display high specificity and sensitivity are required for an effective
struggle against tuberculosis. According to these results, we suggest that
GeneXpert MTB/RIF is a rapid and reliable system, and when used in company with
conventional tests, it would make significant contributions to the diagnosis of
tuberculosis.
PMID- 27511356
TI - Evaluation of new multiplex PCR primers for the identification ofPlasmodium
species found in Sabah, Malaysia.
AB - BACKGROUND/AIM: Malaria is a major public health problem, especially in the
Southeast Asia region, caused by 5 species of Plasmodium (P. falciparum, P.
vivax, P. malariae, P. ovale, and P. knowlesi). The aim of this study was to
compare parasite species identification methods using the new multiplex
polymerase chain reaction (PCR) against nested PCR and microscopy. MATERIALS AND
METHODS: Blood samples on filter papers were subject to conventional PCR methods
using primers designed by us in multiplex PCR and previously designed primers of
nested PCR. Both sets of results were compared with microscopic identification.
RESULTS: Of the 129 samples identified as malaria-positive by microscopy, 15
samples were positive for P. falciparum, 14 for P. vivax, 6 for P. knowlesi, 72
for P. malariae, and 2 for mixed infection of P. falciparum/P. malariae. Both
multiplex and nested PCR identified 12 P. falciparum single infections. For P.
vivax, 9 were identified by multiplex and 12 by nested PCR. For 72 P. malariae
cases, multiplex PCR identified 58 as P. knowlesi and 10 as P. malariae compared
to nested PCR, which identified 59 as P. knowlesi and 7 as P. malariae.
CONCLUSION: Multiplex PCR could be used as alternative molecular diagnosis for
the identification of all Plasmodium species as it requires a shorter time to
screen a large number of samples.
PMID- 27511357
TI - Quantitative comparison of immunohistochemical and PCR analysis of midkine
expression in breast cancer types and serum midkine level.
AB - BACKGROUND/AIM: Midkine (MK), a heparin-binding growth factor, has an important
role in cancer progression. The aim of this study was to determine MK expression
in breast tissue and the preoperative and postoperative serum levels of patients
with breast cancer. MATERIALS AND METHODS: Sixty-one patients with breast cancer
participated in our study. The MK serum levels were measured pre- and
postoperatively for these patients. We also analyzed breast tissues of the 61
patients immunohistochemically. We examined serum midkine levels in 49 healthy
volunteers. RESULTS: MK expression was observed in 44 (72.1%) of 61 breast cancer
patients. In breast cancer patients the serum MK levels (3.68 +/- 2.13 ng/mL
(mean +/- SD)) were significantly higher than in the control group (1.77 +/- 0.38
ng/mL) before tumor removal (P = 0.000). After tumor removal, serum MK levels
(2.47 +/- 1.00 ng/mL) were significantly (P = 0.000) decreased according to
preoperative levels. Increased serum levels of MK were related with tumor stages
when clinical parameters were analyzed. CONCLUSION: We found that increased serum
MK levels and protein expressions were associated with the carcinogenesis of
breast cancer. MK levels decreased after tumor removal. According to our
findings, MK might be a useful tumor marker for patients with breast cancer.
PMID- 27511358
TI - Promoter methylation profile of GSTP1 and RASSF1A in prostate cancerand benign
hyperplasia in Vietnamese men.
AB - BACKGROUND/AIM: The GSTP1 and RASSF1A methylations that were considered as
prostate cancer-specific molecular biomarkers have been extensively reported in
Western/American patients with prostate cancer but are rarely reported in
Southeast Asian patients. In the present study, the methylation status of the
GSTP1 and RASSF1A promoters was evaluated in prostate cancer (PCa) and benign
prostate hyperplasia (BPH) tissues from Vietnamese men. MATERIALS AND METHODS:
The accuracy of methylation-specific polymerase chain reaction (MSP) was
validated to analyze the methylation pattern of GSTP1 and RASSF1A in 59 PCa and
37 BPH patients, respectively. The methylation status was confirmed by the
sequencing of cloned MSP products. The association between methylation status and
the clinical and pathological parameters of tumors was statistically analyzed.
RESULTS: The methylation of GSTP1 and RASSF1A was detected in 39/59 and 19/59 PCa
patients and in 4/37 and 10/37 BPH patients, respectively. The methylation
frequency of GSTP1 was significantly associated with PCa (P < 0.01). The RASSF1A
methylation frequency (32.2%) observed in the study was lower relative to that
detected in other populations. CONCLUSIONS: GSTP1 and RASSF1A methylation was
accurately detected using the validated MSP method and can be used as a biomarker
to diagnose prostate cancer.
PMID- 27511359
TI - Intraarticular Ankaferd blood stopper application increases
cartilagedegeneration: an experimental study.
AB - BACKGROUND/AIM: Ankaferd blood stopper (ABS) is a mixture of certain ratios of 5
different plant roots (Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera,
Alpinia officinarum, and Urtica dioica). The aim of this study is to evaluate the
histopathological effects of ABS on articular cartilage in vitro. MATERIALS AND
METHODS: Twenty-one albino Sprague Dawley rats were randomly allocated to 3
groups: 0.1 mL of saline was injected in the first group, 0.1 mL of ABS was
injected in the second group, and 0.1 mL of blood and 0.1 mL of ABS were injected
in the third group. One month later all rats were sacrificed. Specimens were
obtained for histopathological evaluation. RESULTS: Significant results were
detected in the groups with respect to International Cartilage Repair Society and
synovial proliferation scores (P < 0.05 and P < 0.01). According to inflammatory
cell infiltration and fibrin formation scores, there was no significant
difference between group 1 and group 2 (P < 0.01), although there was significant
difference between group 3 and the other groups (P > 0.05). CONCLUSION: ABS and
hemarthrosis had toxic effects on knee cartilage. The side effects were increased
with the combination of hemarthrosis and ABS. As a result, ABS had unexpected
effects on experimental hemarthrosis.
PMID- 27511360
TI - Clarifying aspects of noninvasive mechanical ventilation in acute exacerbations
of chronic obstructive pulmonary disease.
PMID- 27511361
TI - Nomenclature for factors of the HLA system, update May 2016.
PMID- 27511362
TI - A novel secondary structure based on fused five-membered rings motif.
AB - An analysis of protein structures indicates the existence of a novel, fused five
membered rings motif, comprising of two residues (i and i + 1), stabilized by
interresidue Ni+1-H???Ni and intraresidue Ni+1-H???O=Ci+1 hydrogen bonds. Fused
rings geometry is the common thread running through many commonly occurring
motifs, such as beta-turn, beta-bulge, Asx-turn, Ser/Thr-turn, Schellman motif,
and points to its structural robustness. A location close to the beginning of a
beta-strand is rather common for the motif. Devoid of side chain, Gly seems to be
a key player in this motif, occurring at i, for which the backbone torsion angles
cluster at ~(-90 degrees , -10 degrees ) and (70 degrees , 20 degrees ). The
fused-rings structures, distant from each other in sequence, can hydrogen bond
with each other, and the two segments aligned to each other in a parallel
fashion, give rise to a novel secondary structure, topi, which is quite common in
proteins, distinct from two major secondary structures, alpha-helix and beta
sheet. Majority of the peptide segments making topi are identified as aggregation
prone and the residues tend to be conserved among homologous proteins.
PMID- 27511363
TI - Erratum to: Physicians' responses to computerized drug interaction alerts with
password overrides.
PMID- 27511364
TI - Newly discovered myokines in chronic kidney disease.
PMID- 27511365
TI - Correlation of hepatic fractional extracellular space using gadolinium enhanced
MRI with liver stiffness using magnetic resonance elastography.
AB - PURPOSE: To compare MR hepatic fractional extracellular space (fECS) to liver
stiffness (LS) with magnetic resonance elastography (MRE) for evaluation of liver
fibrosis. METHODS AND MATERIALS: 71 consecutive patients with suspected chronic
liver disease underwent standard liver MRI with MR elastography and additional
delayed Gd-DTPA-enhanced sequences at 5 and 10 min in order to calculate hepatic
fECS (%) and LS (kilopascals, kPa). Two radiologists blinded to clinical history
examined MR images and calculated fECS and LS in identical locations for every
patient. Interobserver agreement was calculated using the intraclass correlation
coefficient. Pearson's correlation was calculated for LS and fECS measures, as
was the area under the receiver operatic curve (AUROC), sensitivity and
specificity of fECS to predict liver stiffness >=2.93 and >=5 kPa. The
sensitivity of fECS for detecting fibrosis was separately analyzed in the
subgroup of patients without anatomic findings of cirrhosis. RESULTS: Substantial
to excellent interobserver agreement for both LS and fECS measurements was seen
with intraclass correlation of 0.88 (95% CI 0.81-0.92) for LS, 0.77 (95% CI 0.66
0.85) for fECS5 and 0.76 (95% CI 0.64-0.84) for fECS10. A significant correlation
was found between MRE and fECS5 (r = 0.47, p < 0.0001) and fECS10 (r = 0.44, p <
0.0001). The performance of fECS improved for detection of advanced fibrosis (>=5
kPa) with AUROC, sensitivity and specificity of 0.72, 38%, and 94% for fECS5 and
0.72, 67%, and 66% for fECS10. CONCLUSION: fECS correlates modestly with MRE
determined LS. fECS at MRI is a simple calculation to perform and may represent a
practical way to suggest the presence of fibrosis during routine liver
evaluation.
PMID- 27511366
TI - MRI for appendicitis in pregnancy: is seeing believing? clinical outcomes in
cases of appendix nonvisualization.
AB - PURPOSE: The primary objective of this study was to determine the clinical
outcomes in cases of appendix nonvisualization with MRI in pregnant patients with
suspected appendicitis and the implications of appendix nonvisualization for
excluding appendicitis. METHODS: Fifty-eight pregnant patients with suspected
appendicitis evaluated with MRI at three centers from a single institution were
retrospectively reviewed by three radiologists with varying levels of abdominal
imaging experience. All scans were performed on a 1.5-Tesla Siemens unit. Cases
were evaluated for diagnostic quality, visualization of the appendix, presence of
appendicitis, and alternate diagnoses. Clinical outcomes were gathered from the
electronic medical record. RESULTS: Of the 58 patients who underwent MRI for
suspected appendicitis, 50 cases were considered adequate diagnostic quality by
all three radiologists. The rate of appendix visualization among the three
radiologists ranged from 60 to 76% (p = 0.44). The appendix was nonvisualized by
at least one of the three radiologists in 25 cases (50%). Of these, none had a
final diagnosis of appendicitis including one patient who underwent appendectomy.
MRI suggested an alternate diagnosis in 6 (24%) patients with appendix
nonvisualization. For the three reviewers, the agreement level on whether or not
the appendix was visualized on the MRI had a Light's kappa value of 0.526,
indicating a "moderate" level of agreement (p value < 0.01). CONCLUSION: Despite
only moderate level of interobserver agreement for appendix visualization,
appendix nonvisualization on MRI in pregnant patients with suspected appendicitis
confers a significant reduction in the risk of appendicitis compared to all
comers as long as the study is adequate diagnostic quality and there are no
secondary signs of appendicitis present.
PMID- 27511367
TI - Morphology and molecular characterization hold hands: clarifying the taxonomy of
Hysterothylacium (Nematoda: Anisakidae) larval forms.
AB - During the last decade, many morphotypes of larval forms of Hysterothylacium have
been proposed; however, their boundaries are taxonomically unclear. We compare
newly collected material with data available for Hysterothylacium larvae, based
on genetics and morphology, in order to evaluate their relationships and simplify
their classification. The previously described Hysterothylacium larval type IV,
type V, and type X were found in several marine fishes from Brazil. A new
Hysterothylacium larval type XV, parasitic in Elops saurus from State of Sergipe,
north-eastern Brazil, was proposed based on its genetic singularity and the
presence of numerous spines throughout the body. Based upon phylogenetic
reconstruction using the ribosomal DNA (rDNA) ITS2 sequences along with
morphological traits, the following third stage larvae were considered valid
(synonyms are inside parenthesis) type III (= types VII and VIII), type V (=
types VI, XII, and XIII), and type X (= type XIV). Despite the lack of molecular
data, Hysterothylacium larval type II is considered as synonym of type I because
of their identical morphology. The morphometry of Hysterothylacium third stage
larvae proved to be weak as a diagnostic tool due to its high rates of variation.
Phylogenetic reconstruction using the concatenated sequences of rDNA ITS1-5.8S
ITS2 and the mitochondrion DNA (mtDNA) cox2 revealed that the sampled
Hysterothylacium larval types V may represent three different species and H.
deardorffovestreetorum may represent two different taxa. Furthermore, H.
deardorffovestreetorum is considered species inquirenda due to its problematic
description and diagnosis which are based only on larvae. A key to
Hysterothylacium larvae from marine fishes is provided.
PMID- 27511368
TI - Toll-like receptors in the brain of mice following infection with Acanthamoeba
spp.
AB - The Toll-like receptors (TLRs) of the innate immune system play an important role
in the recognition of pathogens such as bacteria, viruses, fungi, and parasites.
In this study, we examined the changes in the level of expression of TLR2 and
TLR4 mRNA and protein in the brains of mice infected with Acanthamoeba spp. The
Acanthamoeba strains were isolated from a patient with Acanthamoeba keratitis
(AK) (Ac55) and Malta Lake (Ac43). In the brain isolated from mice at 2 days post
infection (dpi) with Acanthamoeba strains Ac55 and Ac43, mRNAs for TLR2 and TLR4
were significantly more strongly expressed in comparison with the uninfected
mice. In Acanthamoeba-infected mice, TLR2 and TLR4 expression was detected in
neurons, glial cells, and endothelial cells within the neocortex. These receptors
showed more intense expression in ependymocytes of the choroid plexus of infected
mice at 2 dpi. Increased levels of TLR2 and TLR4 mRNA expression in infected mice
suggest the involvement of these TLRs in the recognition of Acanthamoeba spp.
pathogen-associated molecular patterns (PAMPs).
PMID- 27511369
TI - Emergence of Aedes koreicus (Diptera: Culicidae) in an urban area, Hungary, 2016.
AB - In June 2016, three adult females of Aedes koreicus mosquitoes were trapped in
the urban area of Pecs, Southwest Hungary. The introduction of this invasive
mosquito species in this region, along with the recent detection in Germany, may
indicate the capability of the species to spread across Europe. Along with Aedes
albopictus and Aedes japonicus mosquitoes, this is the third invasive mosquito
species occurred in Hungary.
PMID- 27511370
TI - Discovery of DNA dyes Hoechst 34580 and 33342 as good candidates for inhibiting
amyloid beta formation: in silico and in vitro study.
AB - Combining Lipinski's rule with the docking and steered molecular dynamics
simulations and using the PubChem data base of about 1.4 million compounds, we
have obtained DNA dyes Hoechst 34580 and Hoechst 33342 as top-leads for the
Alzheimer's disease. The binding properties of these ligands to amyloid beta
(Abeta) fibril were thoroughly studied by in silico and in vitro experiments.
Hoechst 34580 and Hoechst 33342 prefer to locate near hydrophobic regions with
binding affinity mainly governed by the van der Waals interaction. By the
Thioflavin T assay, it was found that the inhibition constant IC50 ~ 0.86 and
0.68 MUM for Hoechst 34580 and Hoechst 33342, respectively. This result
qualitatively agrees with the binding free energy estimated using the molecular
mechanic-Poisson Boltzmann surface area method and all-atom simulations with the
AMBER-f99SB-ILDN force field and water model TIP3P. In addition, DNA dyes have
the high capability to cross the blood brain barrier. Thus, both in silico and in
vitro experiments have shown that Hoechst 34580 and 33342 are good candidates for
treating the Alzheimer's disease by inhibiting Abeta formation.
PMID- 27511372
TI - Mild heat treatments induce long-term changes in metabolites associated with
energy metabolism in Drosophila melanogaster.
AB - Heat-induced hormesis, the beneficial effect of mild heat-induced stress,
increases the average lifespan of many organisms. Yet little is known about the
mechanisms underlying this effect. We used nuclear magnetic resonance
spectroscopy to investigate the long-term effects of repeated mild heat
treatments on the metabolome of male Drosophila melanogaster. 10 days after the
heat treatment, metabolic aging appears to be slowed down, and a treatment
response with 40 % higher levels of alanine and lactate and lower levels of
aspartate and glutamate were measured. All treatment effects had disappeared 16
days later. Metabolic reprogramming has been associated with the life extending
effects of dietary restriction. The metabolite changes induced by the hormetic
treatment suggest that the positive effects might not be limited to the repair
pathways induced, but that there also is a change in energy metabolism. A
possible direct link between changes in energy metabolism and heat induced
increase in Hsp70 expression is discussed.
PMID- 27511371
TI - Correlation of Cadmium and Magnesium in the Blood and Serum Samples of Smokers
and Non-Smokers Chronic Leukemia Patients.
AB - It was studied that cancer-causing processes are related with the disproportions
of essential and toxic elements in body tissues and fluid. The purpose of the
current study was to evaluate the levels of magnesium (Mg) and cadmium (Cd) in
serum and blood samples of smokers and nonsmokers who have chronic myeloid (CML)
and lymphocytic (CLL) leukemia, age ranged 31-50 years. For comparative study,
age-matched smokers and nonsmoker males were chosen as controls/referents. The
levels of elements in patient were analyzed before any treatment by atomic
absorption spectrophotometer, after microwave assisted acid digestion. The
validation of the method was done by using certified reference materials of serum
and blood samples. The resulted data indicated that the adult male smokers and
nonsmokers have two- to fourfold higher levels of Cd in the blood and sera
samples as compared to the referents (p < 0.01), whereas two- to threefold lower
levels of Mg was found in blood and serum samples of both types of leukemia
patients as related to referent values. The resulted data indicates significant
negative correlation among Mg and Cd in leukemia patients and smoker referents.
Further studies are needed to clarify the role of these elements in pathogenesis
of chronic leukemia.
PMID- 27511373
TI - Comparative RNA-sequencing profiling reveals novel Delta-class glutathione S
transferases relative genes expression patterns in Tribolium castaneum.
AB - Glutathione S-transferases (GSTs) are a large group of enzymes having both
detoxification roles conferring insecticide resistance and specialist metabolic
functions. Tribolium castaneum GST Delta 1 (TcGSTd1) has been found playing
crucial role in insecticide resistance and biological processes in insect
species. However, the regulatory system of TcGSTd1 has still rarely been known.
Comparing the transcriptome profile of RNAi treated larvae (ds-TcGSTd1) and
control larvae of T. canstaneum by using RNA-sequencing, we obtained 14,284,085
sequence reads aligned with 13,275 genes. And 512 differentially expressed genes
(DEGs) were identified from ds-TcGSTd1 treated group. Est/CCE, CYP, MRPs were
significantly down-regulated in ds-TcGSTd1 group when compared with control
group, which illustrated that they cooperated with TcGSTd1 to reduce the activity
of cellular metabolism system. While, SNO was up-regulated in ds-TcGSTd1 insects
suggested it may also involve in detoxifying alkaloid of insect metabolism
system. These results established that TcGSTd1 not only acts as a vital gene for
phase II cellular detoxification but also participates in phase 0, I, and III
cellular detoxification by cooperating with CSPs, OBPs, CYP9, ESTB1, CCE6, MRPs
and other detoxification genes. Knockdown of TcGSTd1 also suppressed several
genes encoding antioxidant enzymes, e.g. CuZnSOD, Duox, Prx, HPX, CPO, and MCORP.
Suggested that they may modulate the function of TcGSTd1 on lifespan, immune,
development and reproduction. All these results shed the new insights into the
regulatory mechanism of TcGSTd1 involved in insect physiology and could further
facilitate the research of suitable and sustainable managements for the pest
control.
PMID- 27511374
TI - LncRNAs expression in adjuvant-induced arthritis rats reveals the potential role
of LncRNAs contributing to rheumatoid arthritis pathogenesis.
AB - BACKGROUND: Long non-coding RNAs (LncRNAs) are an important class of widespread
molecules involved in diverse biological functions, which are exceptionally
expressed in numerous types of diseases. Currently, limited study on LncRNA in
rheumatoid arthritis (RA) is available. In this study, we aimed to identify the
specifically expressed LncRNA that are relevant to adjuvant-induced arthritis
(AA) in rats, and to explore the possible molecular mechanisms of RA
pathogenesis. METHODS: To identify LncRNAs specifically expressed in rheumatoid
arthritis, the expression of LncRNAs in synoviums of rats from the model group
(n=3) was compared with that in the control group (n=3) using Arraystar Rat
LncRNA/mRNA microarray and real-time polymerase chain reaction (RT-PCR). RESULTS:
Up to 260 LncRNAs were found to be differentially expressed (>=1.5-fold-change)
in the synoviums between AA model and the normal rats (170 up-regulated and 90
down-regulated LncRNAs in AA rats compared with normal rats). Coding-non-coding
gene co-expression networks (CNC network) were drawn based on the correlation
analysis between the differentially expressed LncRNAs and mRNAs. Six LncRNAs,
XR_008357, U75927, MRAK046251, XR_006457, DQ266363 and MRAK003448, were selected
to analyze the relationship between LncRNAs and RA via the CNC network and GO
analysis. Real-time PCR result confirmed that the six LncRNAs were specifically
expressed in the AA rats. CONCLUSIONS: These results revealed that clusters of
LncRNAs were uniquely expressed in AA rats compared with controls, which
manifests that these differentially expressed LncRNAs in AA rats might play a
vital role in RA development. Up-regulation or down-regulation of the six LncRNAs
might contribute to the molecular mechanism underlying RA. To sum up, our study
provides potential targets for treatment of RA and novel profound understanding
of the pathogenesis of RA.
PMID- 27511375
TI - Elevated expression of steroidogenesis pathway genes; CYP17, GATA6 and StAR in
prenatally androgenized rats.
AB - It is believed that excess androgen exposure of the fetus, via altered gene
expression, causes hyperandrogenism a key feature of polycystic ovary syndrome
(PCOS). The aim of this study was to evaluate expression of Cytochrome P450-17
(CYP17), GATA-binding protein (GAGT6) and Steroidogenic acute regulatory protein
(StAR), genes of adult female rats prenatally exposed to androgen excess, closely
reflect endocrine and ovarian disturbances of PCOS in women, by comparing them
during different phases of estrus cycle with those of non-treated rats. Both the
adult prenatally testosterone exposed and control rats (n=23, each) were divided
into four groups based on their observed vaginal smear (proestrus, estrus,
metestrus and diestrus) and the relative expression of CYP17, GATA6 and StAR
genes was measured in ovarian theca cells using Cyber-green Real-Time PCR. Serum
sex steroid hormones and gonadotropins levels were measured using the ELISA
method; a comparison of these two groups showed that there was an overall
increase in the studied genes (CYP17; 2.39 fold change, 95% CI: 1.23-3.55;
P<0.05, GATA6; 2.08 fold change, 95% CI: 1.62-2.55; P<0.0001, and StAR; 1.4 fold
change, 95% CI: 1.02-1.78; P<0.05), despite variations in different phases with
maximum elevation for all genes in diestrus. The changes observed may impair the
normal development of ovaries that mediate the programming of adult PCOS.
PMID- 27511376
TI - Nursing home staff should ensure that advance treatment decisions are discussed
with residents and relatives.
PMID- 27511377
TI - Acute gastrointestinal manifestation of situs inversus abdominus.
AB - PURPOSE: Whilst situs inversus is associated with intestinal malrotation and
volvulus particularly in infants, this is the first known report of acute
intestinal obstruction in an adult patient with a situs anomaly specifically due
to a congenital transmesenteric hernia. CASE: A 54-year-old woman presented with
a 12-h history of progressive abdominal pain. Contrast-enhanced computed
tomography scan of the abdomen revealed an incidental finding of situs inversus
abdominus, ischemic small bowel obstruction and a potential occlusive thrombus of
the superior mesenteric artery. At operation, the cause of intestinal obstruction
was found to be secondary to herniation of the intestine through a congenital
mesenteric defect. The hernia was reduced and a strong pulse was subsequently
felt in the distal superior mesenteric artery. The patient required resection of
a segment of compromised small bowel, and was later anastomosed at a planned
second laparotomy. Her laparostomy was closed using an absorbable BioA mesh.
CONCLUSION: A high index of suspicion and low threshold for exploratory surgery
should be maintained in patients with major congenital abdominal anomalies
presenting with an acute abdomen.
PMID- 27511378
TI - Aggressive angiomyxoma presenting as massive irreducible vaginal prolapse.
PMID- 27511379
TI - Knowledge of pelvic floor problems: a study of third trimester, primiparous
women.
AB - INTRODUCTION AND HYPOTHESIS: Pelvic floor problems in women (urinary
incontinence, faecal incontinence, uterovaginal prolapse) are common, and have an
adverse effect on quality of life. We hypothesized that there is low knowledge of
these problems amongst primiparous women in their third trimester of pregnancy.
METHODS: We conducted a cross-sectional study in antenatal clinics of three
hospitals in London, UK, from 2011 to 2013. Primiparous women aged >=18 years and
in the third trimester of pregnancy answered questions on pelvic floor problems.
Knowledge scores were calculated based on the proportion of questions answered
correctly. RESULTS: A total of 249 women completed the question set. The average
knowledge score across all domains was low at 45 %. Scores were lowest for the
less common problems of faecal incontinence (35 %) and prolapse (36 %). The score
for urinary incontinence was higher at 63 %, but low when questions explored more
detailed levels of knowledge (41 %). Knowledge scores were positively associated
with both education to tertiary level and the use of books as the information
source on pregnancy and delivery. Only 35 % of women cited antenatal classes as a
source. CONCLUSIONS: Knowledge of pelvic floor problems is low amongst third
trimester, primiparous women in this London-based population. Adequate knowledge
of these problems is important for women to be able to make informed choices
about their antenatal care and to seek help if problems arise. The data suggest
scope for health-care professionals to raise these issues early during pregnancy,
and to help women access accurate sources of information.
PMID- 27511380
TI - Human tonsil-derived mesenchymal stromal cells enhanced myelopoiesis in a mouse
model of allogeneic bone marrow transplantation.
AB - Mesenchymal stromal cells (MSCs) have therapeutic potential for repairing tissue
damage and are involved in immune regulation. MSCs are predominantly isolated
from bone marrow (BM), adipose tissue or placental tissue. Further to these well
known sources, the isolation of MSCs from human tonsils was previously reported.
The aim of the present study was to investigate a potential role for tonsil
derived MSCs (T-MSCs) in BM reconstitution and application towards supplementing
hematopoiesis in a mouse model of BM transplantation (BMT). Eight-week-old BALB/c
female mice received 80 mg/kg busulfan (Bu)/200 mg/kg cyclophosphamide (Cy)
conditioning chemotherapy for BM ablation. Subsequently, human T-MSCs were
injected into the Bu/Cy-treated mice with or without BM cells (BMCs) obtained
from allogeneic C57BL/6 male mice. After 3 weeks, peripheral blood and BM was
collected for analysis. The red blood cell count in the group that received BMCs
had almost returned to normal, whereas mononuclear cell counts and BM cellularity
were most improved in the T-MSCs + BMCs group. These results indicate that the T
MSCs enhanced myelopoiesis in the allogeneic BMT mouse model, as evidenced by the
restoration of BM with hematopoietic cells, as well as increased myeloid colony
formation in vitro. Therefore, T-MSCs may provide a source of MSCs to facilitate
myelopoiesis and megakaryocytosis following BMT.
PMID- 27511381
TI - Effects of High-cholesterol Diet on Pravastatin Disposition in the Perfused Rat
Liver.
AB - BACKGROUND AND OBJECTIVES: Various nutrients modulate the expression of
transporters; however, the effect of a high-cholesterol (HC) diet on the
expression and function of hepatic transporters remains unclear. Here, we
examined the effects of an HC diet on drug disposition via hepatic transporters,
including organic anion-transporting polypeptide (Oatp), multidrug resistance
associated protein (Mrp), and bile salt export pump (Bsep). METHODS: In situ
perfused rat liver system was performed. The levels of pravastatin, which is
taken up into hepatocytes by Oatp and excreted into bile by Mrp2, in the
perfusate and in bile were measured using high-performance liquid chromatography.
RESULTS: Pravastatin was rapidly eliminated in control and HC rats; however, the
cumulative amounts of excreted in bile were significantly higher in HC rats than
in controls possibly because of the enhanced bile flow in HC rats (0.93 +/- 0.05
MUL/min in control, and 1.22 +/- 0.18 MUL/min in HC). Real-time reverse
transcriptase polymerase chain reaction (PCR) and western blot assessment of the
mRNA and protein levels of hepatic transporters showed a significant
downregulation of the Oatp1a1 and Bsep proteins in HC rats, whereas no
differences in Mrp2 and Mrp3 levels were observed between HC and control rats.
The analysis of the localization of Mrp2 on the canalicular membrane by
immunofluorescence showed no changes in HC rats, although Mrp2 was readily
internalized from the canalicular membrane under specific conditions.
CONCLUSIONS: The findings of the present study indicate that the HC diet affected
the biliary excretion of pravastatin concomitant with increased bile flow,
despite minimal effects on the expression of hepatic transporters. The HC diet
could promote the biliary excretion of other drugs and metabolites that are
substrates of Mrp2 and Bsep.
PMID- 27511382
TI - Gestational diabetes mellitus: an evaluation of gynecologists' knowledge of
guidelines and counseling behavior.
AB - PURPOSE: Knowledge of risks, adequate pre- and post-partum care, and counseling
is essential to reduce short- and long-term consequences for women with
gestational diabetes mellitus (GDM) and their offspring. Our study explored the
current GDM guideline knowledge and practiced patient counseling of private
gynecologists in Germany. METHODS: A survey assessing the GDM guidelines and
patient counseling was mailed to 775 practicing gynecologists. We evaluated the
knowledge of maternal and offspring disease risks, counseling practice, and
guideline awareness. Descriptive statistics were used to analyze the responses
and Chi-Square or Fisher exact test to explore differences between groups.
RESULTS: Of the 418 private gynecologists (54.1 % response rate) who responded,
the majority was aware of obesity and GDM in the previous pregnancy as risk
factors for GDM. To a lesser extent, risk factors like recurrent miscarriages and
stillbirth were recalled. Eighty percent stated that GDM was associated with a
higher risk for the development for hypertension and 96 % with type 2 diabetes in
the mother. Respondents with knowledge of the current GDM guidelines were more
often aware of the development of chronic diseases, counseled patients more
frequently, and performed post-partum glucose screenings more regularly compared
with private gynecologists with no knowledge of the guidelines. CONCLUSIONS: The
majority of participants incorporated recent recommendations into their practice
patterns for GDM. Providing private gynecologists with additional training may
further improve care for women with GDM-affected pregnancies.
PMID- 27511384
TI - Junior doctors will have whistleblowing protection added to contracts.
PMID- 27511432
TI - Case of a neutrophilic dermatosis involving lung abscess after influenza
vaccination.
PMID- 27511383
TI - Gaze data reveal distinct choice processes underlying model-based and model-free
reinforcement learning.
AB - Organisms appear to learn and make decisions using different strategies known as
model-free and model-based learning; the former is mere reinforcement of
previously rewarded actions and the latter is a forward-looking strategy that
involves evaluation of action-state transition probabilities. Prior work has used
neural data to argue that both model-based and model-free learners implement a
value comparison process at trial onset, but model-based learners assign more
weight to forward-looking computations. Here using eye-tracking, we report
evidence for a different interpretation of prior results: model-based subjects
make their choices prior to trial onset. In contrast, model-free subjects tend to
ignore model-based aspects of the task and instead seem to treat the decision
problem as a simple comparison process between two differentially valued items,
consistent with previous work on sequential-sampling models of decision making.
These findings illustrate a problem with assuming that experimental subjects make
their decisions at the same prescribed time.
PMID- 27511433
TI - An Assessment of Coherence Between Early Warning and Response Systems and Serious
Cross-Border Health Threats in the European Union and Turkey.
AB - Disease outbreaks have attracted the attention of the public health community to
early warning and response systems (EWRS) for communicable diseases and other
cross-border threats to health. The European Union (EU) and the World Health
Organization (WHO) have published regulations in this area. Decision 1082/2013/EU
brought a new approach the management of public health threats in EU member
states. Decision 1082/2013/EU brought several innovations, which included
establishing a Health Security Committee; preparedness and response planning;
joint procurement of medical countermeasures; ad hoc monitoring for biological,
chemical, and environmental threats; EWRS; and recognition of an emergency
situation and interoperability between various sectors. Turkey, as an acceding
country to the EU and a member of the WHO, has been improving its national public
health system to meet EU legislations and WHO standards. This article first
explains EWRS as defined in Decision 1082/2013/EU and Turkey's obligations to
align its public health laws to the EU acquis. EWRS in Turkey are addressed,
particularly their coherence with EU policies regarding preparedness and
response, alert notification, and interoperability between health and other
sectors. Finally, the challenges and limitations of the current Turkish system
are discussed and further improvements are suggested. (Disaster Med Public Health
Preparedness. 2016;10:883-892).
PMID- 27511434
TI - Porous V2O5/RGO/CNT hierarchical architecture as a cathode material: Emphasis on
the contribution of surface lithium storage.
AB - A three dimensional vanadium pentoxide/reduced graphene oxide/carbon nanotube (3D
V2O5/RGO/CNT) composite is synthesized by microwave-assisted hydrothermal method.
The combination of 2D RGO and 1D CNT establishes continuous 3D conductive
network, and most notably, the 1D CNT is designed to form hierarchically porous
structure by penetrating into V2O5 microsphere assembly constituted of numerous
V2O5 nanoparticles. The highly porous V2O5 microsphere enhances electrolyte
contact and shortens Li(+) diffusion path as a consequence of its developed
surface area and mesoporosity. The successive phase transformations of 3D
V2O5/RGO/CNT from alpha-phase to epsilon-, delta-, gamma-, and omega-phase and
its structural reversibility upon Li(+) intercalation/de-intercalation are
investigated by in situ XRD analysis, and the electronic and local structure
reversibility around vanadium atom in 3D V2O5/RGO/CNT is observed by in situ
XANES analysis. The 3D V2O5/RGO/CNT achieves a high capacity of 220 mAh g(-1) at
1 C after 80 cycles and an excellent rate capability of 100 mAh g(-1) even at a
considerably high rate of 20 C. The porous 3D V2O5/RGO/CNT structure not only
provides facile Li(+) diffusion into bulk but contributes to surface Li(+)
storage as well, which enables the design of 3D V2O5/RGO/CNT composite to become
a promising cathode architecture for high performance LIBs.
PMID- 27511435
TI - Supersonic shearwave elastography in the assessment of liver fibrosis for
postoperative patients with biliary atresia.
AB - To explore an effective noninvasive tool for monitoring liver fibrosis of
children with biliary atresia (BA) is important but evidences are limited. This
study is to investigate the predictive accuracy of supersonic shearwave
elastography (SSWE) in liver fibrosis for postoperative patients with BA and to
compare it with aspartate aminotransferase to platelet ratio index (APRI) and
fibrosis-4 (FIB-4). 24 patients with BA received SSWE and laboratory tests before
scheduled for liver biopsy. Spearman rank coefficient and receiver operating
characteristic (ROC) were used to analyze data. Metavir scores were F0 in 3, F1
in 2, F2 in 4, F3 in 7 and F4 in 8 patients. FIB-4 failed to correlate with
fibrosis stage. The areas under the ROC curves of SSWE, APRI and their
combination were 0.79, 0.65 and 0.78 for significant fibrosis, 0.81, 0.64 and
0.76 for advanced fibrosis, 0.82, 0.56 and 0.84 for cirrhosis. SSWE values at
biopsy was correlated with platelet count (r = -0.426, P = 0.038), serum albumin
(r = -0.670, P < 0.001), total bilirubin (r = 0.419, P = 0.041) and direct
bilirubin levels (r = 0.518, P = 0.010) measured at 6 months after liver biopsy.
Our results indicate that SSWE is a more promising tool to assess liver fibrosis
than APRI and FIB-4 in children with BA.
PMID- 27511436
TI - Small bowel neuroendocrine tumors: A critical analysis of diagnostic work-up and
operative approach.
AB - BACKGROUND: Small bowel neuroendocrine tumors (SB-NETs) are often small,
multifocal, difficult to localize preoperatively, and can be overlooked during
operative exploration. The optimal work-up and operative approach is unknown.
METHODS: Patients who underwent resection of SB-NETs at a single-institution from
2000 to 2014 were included. Primary aim was to describe the diagnostic work-up
and compare minimally invasive (MIS) to open resection. RESULTS: Ninety-three
patients underwent resection for SB-NETs. About 71% were symptomatic and on
average underwent three diagnostic tests: 45% had octreoscans (85% diagnostic
yield); 11% had SB-enteroscopy (10% yield); 19% had capsule endoscopy (83% yield,
but identified the correct tumor number in only 21%). About 27 pts underwent MIS
versus 66 open. MIS pts were younger (56 vs. 61 yrs; P = 0.035), and less likely
to have obstruction (4% vs. 24%; P = 0.019) and metastases (19% vs. 44%; P =
0.038). Compared to open, MIS had smaller (1.7 vs. 2.4 cm; P = 0.03) and fewer
tumors resected (2 vs. 5; P = 0.049), but similar LN yield (13 vs. 12; P = 0.7).
In non-metastatic, curative-intent resections, MIS still resected fewer tumors
compared to open (1.5 vs. 4; P = 0.034). CONCLUSION: Capsule endoscopy may be
better than small bowel enteroscopy at identifying occult SB-NETs, but may
underestimate tumor burden. While MIS may be appropriate in select patients,
recognizing the limitations of preoperative evaluation is critical for these
tumors, as heightened operative vigilance is often required. J. Surg. Oncol.
2016;114:671-676. (c) 2016 Wiley Periodicals, Inc.
PMID- 27511438
TI - Why are sec-alkylperoxyl bimolecular self-reactions orders of magnitude faster
than the analogous reactions of tert-alkylperoxyls? The unanticipated role of CH
hydrogen bond donation.
AB - High-level ab initio calculations are used to identify the mechanism of secondary
(and primary) alkylperoxyl radical termination and explain why their reactions
are much faster than their tertiary counterparts. Contrary to existing
literature, the decomposition of both tertiary and non-tertiary tetroxides
follows the same asymmetric two-step bond cleavage pathway to form a caged
intermediate of overall singlet multiplicity comprising triplet oxygen and two
alkoxyl radicals. The alpha hydrogen atoms of non-tertiary species facilitate
this process by forming unexpected CHO hydrogen bonds to the evolving O2. For non
tertiary peroxyls, subsequent alpha hydrogen atom transfer then yields the
experimentally observed non-radical products, ketone, alcohol and O2, whereas for
tertiary species, this reaction is precluded and cage escape of the (unpaired)
alkoxyl radicals is a likely outcome with important consequences for
autoxidation.
PMID- 27511437
TI - Spanish-Language Consumer Health Information Technology Interventions: A
Systematic Review.
AB - BACKGROUND: As consumer health information technology (IT) becomes more
thoroughly integrated into patient care, it is critical that these tools are
appropriate for the diverse patient populations whom they are intended to serve.
Cultural differences associated with ethnicity are one aspect of diversity that
may play a role in user-technology interactions. OBJECTIVE: Our aim was to
evaluate the current scope of consumer health IT interventions targeted to the US
Spanish-speaking Latino population and to characterize these interventions in
terms of technological attributes, health domains, cultural tailoring, and
evaluation metrics. METHODS: A narrative synthesis was conducted of existing
Spanish-language consumer health IT interventions indexed within health and
computer science databases. Database searches were limited to English-language
articles published between January 1990 and September 2015. Studies were included
if they detailed an assessment of a patient-centered electronic technology
intervention targeting health within the US Spanish-speaking Latino population.
Included studies were required to have a majority Latino population sample. The
following were extracted from articles: first author's last name, publication
year, population characteristics, journal domain, health domain, technology
platform and functionality, available languages of intervention, US region,
cultural tailoring, intervention delivery location, study design, and evaluation
metrics. RESULTS: We included 42 studies in the review. Most of the studies were
published between 2009 and 2015 and had a majority percentage of female study
participants. The mean age of participants ranged from 15 to 68. Interventions
most commonly focused on urban population centers and within the western region
of the United States. Of articles specifying a technology domain, computer was
found to be most common; however, a fairly even distribution across all
technologies was noted. Cancer, diabetes, and child, infant, or maternal health
were the most common health domains targeted by consumer health IT interventions.
More than half of the interventions were culturally tailored. The most frequently
used evaluation metric was behavior/attitude change, followed by usability and
knowledge retention. CONCLUSIONS: This study characterizes the existing body of
research exploring consumer health IT interventions for the US Spanish-speaking
Latino population. In doing so, it reveals three primary needs within the field.
First, while the increase in studies targeting the Latino population in the last
decade is a promising advancement, future research is needed that focuses on
Latino subpopulations previously overlooked. Second, preliminary steps have been
taken to culturally tailor consumer health IT interventions for the US Spanish
speaking Latino population; however, focus must expand beyond intervention
content. Finally, the field should work to promote long-term evaluation of
technology efficacy, moving beyond intermediary measures toward measures of
health outcomes.
PMID- 27511439
TI - Cadmium-induced immune abnormality is a key pathogenic event in human and rat
models of preeclampsia.
AB - With increased industrial development, cadmium is an increasingly important
environmental pollutant. Studies have identified various adverse effects of
cadmium on human beings. However, the relationships between cadmium pollution and
the pathogenesis of preeclampsia remain elusive. The objective of this study is
to explore the effects of cadmium on immune system among preeclamptic patients
and rats. The results showed that the cadmium levels in the peripheral blood of
preeclamptic patients were significantly higher than those observed in normal
pregnancy. Based on it, a novel rat model of preeclampsia was established by the
intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg
body weight) on gestational days 9-14. Key features of preeclampsia, including
hypertension, proteinuria, placental abnormalities and small foetal size,
appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium
increased immunoglobulin production, mainly angiotensin II type 1-receptor
agonistic autoantibodies (AT1-AA), by increasing the expression of activation
induced cytosine deaminase (AID) in B cells. AID is critical for the maturation
of antibody and autoantibody responses. In addition, angiotensin II type 1
receptor-agonistic autoantibody, which emerged recently as a potential pathogenic
contributor to PE, was responsible for the deposition of complement component 5
(C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R)
activation. C5a is a fragment of C5 that is released during C5 activation.
Selectively interfering with C5a signalling by a complement C5a receptor-specific
antagonist significantly attenuated hypertension and proteinuria in Cd-injected
pregnant rats. Our results suggest that cadmium induces immune abnormalities that
may be a key pathogenic contributor to preeclampsia and provide new insights into
treatment strategies of preeclampsia.
PMID- 27511440
TI - Comparisons of discrete and integrative sampling accuracy in estimating pulsed
aquatic exposures.
AB - Most current-use pesticides have short half-lives in the water column and thus
the most relevant exposure scenarios for many aquatic organisms are pulsed
exposures. Quantifying exposure using discrete water samples may not be accurate
as few studies are able to sample frequently enough to accurately determine time
weighted average (TWA) concentrations of short aquatic exposures. Integrative
sampling methods that continuously sample freely dissolved contaminants over time
intervals (such as integrative passive samplers) have been demonstrated to be a
promising measurement technique. We conducted several modeling scenarios to test
the assumption that integrative methods may require many less samples for
accurate estimation of peak 96-h TWA concentrations. We compared the accuracies
of discrete point samples and integrative samples while varying sampling
frequencies and a range of contaminant water half-lives (t50 = 0.5, 2, and 8 d).
Differences the predictive accuracy of discrete point samples and integrative
samples were greatest at low sampling frequencies. For example, when the half
life was 0.5 d, discrete point samples required 7 sampling events to ensure
median values > 50% and no sampling events reporting highly inaccurate results
(defined as < 10% of the true 96-h TWA). Across all water half-lives
investigated, integrative sampling only required two samples to prevent highly
inaccurate results and measurements resulting in median values > 50% of the true
concentration. Regardless, the need for integrative sampling diminished as water
half-life increased. For an 8-d water half-life, two discrete samples produced
accurate estimates and median values greater than those obtained for two
integrative samples. Overall, integrative methods are the more accurate method
for monitoring contaminants with short water half-lives due to reduced frequency
of extreme values, especially with uncertainties around the timing of pulsed
events. However, the acceptability of discrete sampling methods for providing
accurate concentration measurements increases with increasing aquatic half-lives.
PMID- 27511441
TI - A Novel Trihybrid Material Based on Renewables: An Efficient Recyclable
Heterogeneous Catalyst for C-C Coupling and Reduction Reactions.
AB - The generation of organic-inorganic hybrid materials from renewable resources and
their utilization in basic and applied areas has been at the forefront of
research in recent years for sustainable development. Herein, a novel organic
inorganic trihybrid material was synthesized by in situ generation of palladium
nanoparticles (PdNPs) in a hybrid gel matrix based on renewable chemicals.
Constituents of the hybrid gel included a pentacyclic triterpenoid arjunolic acid
extractable from Terminalia arjuna and the leaf extract of Chrysophyllum cainito
rich in flavonoids. We took advantage of the presence of flavonoid molecules in
this hybrid gel to generate an advanced trihybrid gel through in situ reduction
of doped Pd(II) salts to stable PdNPs. The xerogel of this trihybrid material was
used as a recyclable heterogeneous catalyst for C-C coupling and reduction
reactions in aqueous media. We also demonstrated that the in situ generated PdNPs
containing trihybrid material was a more efficient catalyst than the trihybrid
material generated with presynthesized PdNPs.
PMID- 27511442
TI - Unravelling Li-Ion Transport from Picoseconds to Seconds: Bulk versus Interfaces
in an Argyrodite Li6PS5Cl-Li2S All-Solid-State Li-Ion Battery.
AB - One of the main challenges of all-solid-state Li-ion batteries is the restricted
power density due to the poor Li-ion transport between the electrodes via the
electrolyte. However, to establish what diffusional process is the bottleneck for
Li-ion transport requires the ability to distinguish the various processes. The
present work investigates the Li-ion diffusion in argyrodite Li6PS5Cl, a
promising electrolyte based on its high Li-ion conductivity, using a combination
of (7)Li NMR experiments and DFT based molecular dynamics simulations. This
allows us to distinguish the local Li-ion mobility from the long-range Li-ion
motional process, quantifying both and giving a coherent and consistent picture
of the bulk diffusion in Li6PS5Cl. NMR exchange experiments are used to
unambiguously characterize Li-ion transport over the solid electrolyte-electrode
interface for the electrolyte-electrode combination Li6PS5Cl-Li2S, giving
unprecedented and direct quantitative insight into the impact of the interface on
Li-ion charge transport in all-solid-state batteries. The limited Li-ion
transport over the Li6PS5Cl-Li2S interface, orders of magnitude smaller compared
with that in the bulk Li6PS5Cl, appears to be the bottleneck for the performance
of the Li6PS5Cl-Li2S battery, quantifying one of the major challenges toward
improved performance of all-solid-state batteries.
PMID- 27511443
TI - NSAID-induced symptomatic hypophosphataemia.
PMID- 27511444
TI - Radiofrequency ablation compared with laparoscopic adrenalectomy for aldosterone
producing adenoma.
AB - BACKGROUND: Radiofrequency ablation (RFA) is an emerging treatment for primary
aldosteronism owing to aldosterone-producing adenoma. Whether RFA could be an
alternative treatment to laparoscopic adrenalectomy is unknown. METHODS: This was
a retrospective comparative study in patients with aldosterone-producing adenoma
undergoing either laparoscopic adrenalectomy or CT-guided percutaneous RFA
between 2004 and 2012. Short-term outcomes and long-term resolution rates of
primary aldosteronism (normalized aldosterone to renin ratio), hypokalaemia and
hypertension (BP lower than 140/90 mmHg without antihypertensive medical therapy)
were evaluated. RESULTS: Some 63 patients were included, 27 in the laparoscopic
adrenalectomy group and 36 in the RFA group. RFA was associated with shorter
duration of operation (median 12 versus 124 min; P < 0.001), shorter hospital
stay (2 versus 4 days; P < 0.001), lower analgesic requirements (13 of 36 versus
23 of 27 patients; P < 0.001) and earlier resumption of work (median 4 versus 14
days; P = 0.006). Morbidity rates were similar in the two groups. With median
follow-up of 5.7 (range 1.9-10.6) years, resolution of primary aldosteronism was
seen in 33 of 36 patients treated with RFA and all 27 patients who had
laparoscopic adrenalectomy (P = 0.180). Hypertension was resolved less frequently
after treatment with RFA compared with laparoscopic adrenalectomy (13 of 36
versus 19 of 27 patients; P = 0.007). Hypokalaemia was resolved in all patients.
CONCLUSION: For patients with aldosterone-producing adenoma the efficacy of
resolution of primary aldosteronism and hypertension was inferior after treatment
with RFA compared with laparoscopic adrenalectomy.
PMID- 27511446
TI - Five-year clinical performance of a biodegradable polymer-coated biolimus-eluting
stent in unselected patients.
AB - OBJECTIVE: To evaluate the long-term follow-up of the unrestricted use of a
biodegradable polymer-coated drug-eluting stent in patients undergoing
percutaneous coronary intervention (PCI). METHODS: The Nobori 2 study was a
prospective, multicentre, observational registry evaluating the safety and the
efficacy of the biodegradable polymer biolimus-eluting stent (BP-BES) among 3067
patients recruited at 125 international sites. The primary combined endpoint was
a composite of cardiac death, myocardial infarction and target-lesion
revascularisation (TLR). RESULTS: Five-year follow-up was available in 2738
(89.3%) patients. The combined endpoint occurred in 268 patients (10%, 95% CIs
8.9% to 11.3%) at 5 years, with 3.9% of events during the first year and 6.2%
during years 1-5 of follow-up. Cumulative rates of TLR and definite/probable
stent thrombosis were 5.3% (95% CI 4.5% to 6.3%) and 1.1% (95% CI 0.8% to 1.6%),
respectively. Between 1 and 5 years, TLR and very late stent thrombosis rates
were 3.5% (95% CI 2.8% to 4.4%) and 0.6% (95% CI 0.3% to 1.1%), respectively.
Previous PCI (HR, 2.05, 95% CI 1.68 to 2.50), moderate-to-severe renal disease
(HR, 1.89, 95% CI 1.30 to 2.74) and peripheral vascular disease (HR, 1.86, 95% CI
1.38 to 2.52) were the three most powerful independent predictors of the combined
endpoint at 5 years. CONCLUSIONS: The final 5-year follow-up of the Nobori 2
registry demonstrates the safety and effectiveness of the BP-BES in an
unselected, broadly inclusive cohort of PCI patients, highlighting the excellent
performance of this coronary stent technology after polymer biodegradation. TRIAL
REGISTRATION NUMBER: ISRCTN81649913; Results.
PMID- 27511445
TI - Gene expression of muscular and neuronal pathways is cooperatively dysregulated
in patients with idiopathic achalasia.
AB - Idiopathic achalasia is characterized by the absence of peristalsis secondary to
loss of neurons in the myenteric plexus that hampers proper relaxation of the
lower esophageal sphincter. Achalasia can be considered a multifactorial disorder
as it occurs in related individuals and is associated with HLA class II genes,
thereby suggesting genetic influence. We used microarray technology and advanced
in-silico functional analyses to perform the first genome-wide expression
profiling of mRNA in tissue samples from 12 achalasia and 5 control patients. It
revealed 1,728 differentially expressed genes, of these, 837 (48.4%) were up
regulated in cases. In particular, genes participating to the smooth muscle
contraction biological function were mostly up-regulated. Functional analysis
revealed a significant enrichment of neuronal/muscular and neuronal/immunity
processes. Upstream regulatory analysis of 180 genes involved in these processes
suggested TLR4 and IL18 as critical key-players. Two functional gene networks
were significantly over-represented: one involved in organ morphology, skeletal
muscle system development and function, and neurological diseases, and the other
participating in cell morphology, humoral immune response and cellular movement.
These results highlight on pivotal genes that may play critical roles in
neuronal/muscular and neuronal/immunity processes, and that may contribute to the
onset and development of achalasia.
PMID- 27511447
TI - Pregnancy outcomes in patients with pulmonary arterial hypertension associated
with congenital heart disease.
AB - OBJECTIVE: There is growing evidence that maternal mortality in pregnant women
with pulmonary arterial hypertension associated with congenital heart disease
(PAH-CHD) is lower than that in available data. In order to evaluate this
hypothesis, we collected data of pregnancies in women with PAH-CHD. METHODS:
Women with PAH-CHD followed in seven French referral centres were retrospectively
included from 1997 to 2015. All pregnancies were recorded. We collected data on
maternal, obstetrical and neonatal outcomes. RESULTS: 28 pregnancies in 20 women
(26+/-6 years old) with PAH-CHD were managed during this period. There were 18
complete pregnancies (>=20 weeks' gestation (WG)), 8 abortions and 2
miscarriages. Six (33%, 95% CI (11.9 to 54.3)) patients experienced severe
cardiac events. The concerned women had lower resting oxygen saturation (79.6+/
4.1% vs 89.3+/-3.8%, p<0.01). The most common cardiac complications during the
complete pregnancies were heart failure (n=4) and severe hypoxaemia (n=5). Heart
failure was overall severe, requiring inotropic treatment in three patients,
mechanical circulatory support in one and led to one maternal death
(mortality=5.0% 95% CI (0.1 to 24.9)). Obstetrical complications occurred in 25%
of pregnancies. Small for gestational age was diagnosed in 39% (7/18) of fetuses.
12/18 (67%) pregnancies were delivered by caesarean section, of which 10 in
emergency for obstetrical reason. Prematurity was frequent (78%), but no neonatal
death occurred. CONCLUSIONS: Outcome of pregnancy in women with PAH-CHD is better
than previously reported, with only 5% maternal mortality in our cohort. However,
because of the severity of heart failure and the high rate of neonatal
complications, patients should still be advised against pregnancy.
PMID- 27511449
TI - Corrigendum.
AB - [This corrects the article DOI: 10.1111/rcr2.151.].
PMID- 27511448
TI - Posttraumatic stress disorder under ongoing threat: a review of neurobiological
and neuroendocrine findings.
AB - BACKGROUND: Although numerous studies have investigated the neurobiology and
neuroendocrinology of posttraumatic stress disorder (PTSD) after single finished
trauma, studies on PTSD under ongoing threat are scarce and it is still unclear
whether these individuals present similar abnormalities. OBJECTIVE: The purpose
of this review is to present the neurobiological and neuroendocrine findings on
PTSD under ongoing threat. Ongoing threat considerably affects PTSD severity and
treatment response and thus disentangling its neurobiological and neuroendocrine
differences from PTSD after finished trauma could provide useful information for
treatment. METHOD: Eighteen studies that examined brain functioning and cortisol
levels in relation to PTSD in individuals exposed to intimate partner violence,
police officers, and fire fighters were included. RESULTS: Hippocampal volume was
decreased in PTSD under ongoing threat, although not consistently associated with
symptom severity. The neuroimaging studies revealed that PTSD under ongoing
threat was not characterized by reduced volume of amygdala or parahippocampal
gyrus. The neurocircuitry model of PTSD after finished trauma with
hyperactivation of amygdala and hypoactivation of prefrontal cortex and
hippocampus was also confirmed in PTSD under ongoing threat. The neuroendocrine
findings were inconsistent, revealing increased, decreased, or no association
between cortisol levels and PTSD under ongoing threat. CONCLUSIONS: Although PTSD
under ongoing threat is characterized by abnormal neurocircuitry patterns similar
to those previously found in PTSD after finished trauma, this is less so for
other neurobiological and in particular neuroendocrine findings. Direct
comparisons between samples with ongoing versus finished trauma are needed in
future research to draw more solid conclusions before administering cortisol to
patients with PTSD under ongoing threat who may already exhibit increased
endogenous cortisol levels.
PMID- 27511450
TI - Clinical-pathologic correlations in voltage-gated Kv1 potassium channel complex
subtyped autoimmune painful polyneuropathy.
AB - INTRODUCTION: Voltage-gated Kv1 potassium channel complex (VGKC) autoantibodies
subtyped for leucine-rich glioma-inactivated 1 (LGI1), contactin-associated
proteinlike 2 (CASPR2), and Kv IgGs have a spectrum of neurological
presentations. Painful polyneuropathy is seen in some patients, but nerve
pathology descriptions are lacking. METHODS: Clinicopathologic features were
studied in subtyped VGKC-autoantibody-seropositive patients who had undergone
nerve biopsies. RESULTS: Five patients were identified, 1 LGI1 IgG positive and 1
CASPR2 IgG positive, but all negative for Kv1.1-, 1.2-, 1.6-subtyped IgG
autoantibodies. Median symptom duration was 17 months. Pain was the predominant
symptom; 3 had mild sensory loss and/or weakness. Histopathological abnormalities
were limited to axonal loss in 3. None had mononuclear cellular infiltrates.
Electron micrographs revealed no interstitial abnormalities. Three patients
reported marked improvement in pain with immunotherapy. CONCLUSIONS: The nerve
biopsy histopathology of patients subtyped for LGI1 and CASPR2 IgGs within the
VGKC-complex spectrum disorders shows either normal density or axonal fiber loss
without inflammatory infiltrates. A reversible neural hyperexcitable mechanism is
considered to be the cause of this painful polyneuropathy. Muscle Nerve 55: 520
525, 2017.
PMID- 27511452
TI - Effects of exogenous testosterone and mating context on men's preferences for
female facial femininity.
AB - Correlational research suggests that men show greater attraction to feminine
female faces when their testosterone (T) levels are high. Men's preferences for
feminine faces also seem to vary as a function of relationship context (short
versus long-term). However, the relationship between T and preferences for female
facial femininity has yet to be tested experimentally. In the current paper, we
report the results of two experiments examining the causal role of T in
modulating preferences for facial femininity across both short and long-term
mating contexts. Results of Experiment 1 (within-subject design, n=24) showed
that participants significantly preferred feminized versus masculinized versions
of women's faces. Further, participants showed a stronger preference for feminine
faces in the short versus the long-term context after they received T, but not
after they received placebo. Post-hoc analyses suggested that this effect was
driven by a lower preference for feminine faces in the long-term context when on
T relative to placebo, and this effect was found exclusively for men who received
placebo on the first day of testing, and T on the second day of testing (i.e.,
Order x Drug x Mating context interaction). In Experiment 2 (between-subject
design, n=93), men demonstrated a significant preference for feminized female
faces in the short versus the long-term context after T, but not after placebo
administration. Collectively, these findings provide the first causal evidence
that T modulates men's preferences for facial femininity as a function of mating
context.
PMID- 27511451
TI - NIR Light Propulsive Janus-like Nanohybrids for Enhanced Photothermal Tumor
Therapy.
AB - Au-BP7@SP nanohybrids with active motion under NIR laser irradiation can
effectively enhance the temperature of tumor potentially by converting the
kinetic energy to thermal energy, enhancing the killing efficiency of the tumor
cells compared with Au@SP. The study provides an insight of nanohybrids' effect
on photothermal treatment and opens a new avenue to cancer treatment by using
self-propulsion Janus nanohybrids.
PMID- 27511453
TI - Identification of proteomic and metabolic signatures associated with
chemoresistance of human epithelial ovarian cancer.
AB - Emerging drug resistance in epithelial ovarian cancer (EOC) thwarted progress in
platinum-based chemotherapy, resulting in increased mortality, morbidity and
healthcare costs. The aim of this study was to detect the responses induced by
chemotherapy at protein and metabolite levels, and to search for new plasma
markers that can predict resistance to platinum-based chemotherapy in EOC
patients, leading to improved clinical response rates. Serum samples were
collected and subjected to proteomic relative quantitation analysis and
metabolomic analysis. Differentially expressed proteins and metabolites were
subjected to bioinformatics and statistical analysis. Proteins that played a key
role in platinum resistance were validated by western blotting and enzyme-linked
immunosorbent assay (ELISA). Metabolites that were the main contributors to the
groups and closely with clinical characteristics were identified based on the
database using nuclear magnetic resonance (NMR). In total, 248 proteins from two
independent experiments were identified using isobaric tags for relative and
absolute quantitation (iTRAQ)-based quantitative proteomic approach. Among them,
FN1, SERPINA1, GPX3 and ORM1 were chosen for western blotting and ELISA
validation. Platinum resistance likely associated with differentially expressed
proteins and FN1, SERPINA1 and ORM1 may play a positive role in chemotherapy.
HPLC-MS analysis of four groups revealed a total of 25,800 metabolic features, of
which six compounds were chosen for candidate biomarkers and identified based on
the database using NMR. The metabolic signatures of normal control (NC), platinum
sensitive (PTS) and platinum-resistant (PTR) groups were clearly separated from
each other. Those findings may provide theoretical clues for the prediction of
chemotherapeutic response and reverse of drug resistance, even lead to novel
targets for therapeutic intervention.
PMID- 27511454
TI - Implementation errors in the GingerALE Software: Description and recommendations.
AB - Neuroscience imaging is a burgeoning, highly sophisticated field the growth of
which has been fostered by grant-funded, freely distributed software libraries
that perform voxel-wise analyses in anatomically standardized three-dimensional
space on multi-subject, whole-brain, primary datasets. Despite the ongoing
advances made using these non-commercial computational tools, the replicability
of individual studies is an acknowledged limitation. Coordinate-based meta
analysis offers a practical solution to this limitation and, consequently, plays
an important role in filtering and consolidating the enormous corpus of
functional and structural neuroimaging results reported in the peer-reviewed
literature. In both primary data and meta-analytic neuroimaging analyses,
correction for multiple comparisons is a complex but critical step for ensuring
statistical rigor. Reports of errors in multiple-comparison corrections in
primary-data analyses have recently appeared. Here, we report two such errors in
GingerALE, a widely used, US National Institutes of Health (NIH)-funded, freely
distributed software package for coordinate-based meta-analysis. These errors
have given rise to published reports with more liberal statistical inferences
than were specified by the authors. The intent of this technical report is
threefold. First, we inform authors who used GingerALE of these errors so that
they can take appropriate actions including re-analyses and corrective
publications. Second, we seek to exemplify and promote an open approach to error
management. Third, we discuss the implications of these and similar errors in a
scientific environment dependent on third-party software. Hum Brain Mapp 38:7-11,
2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27511455
TI - Linking microbial diversity and functionality of arctic glacial surface habitats.
AB - Distinct microbial habitats on glacial surfaces are dominated by snow and ice
algae, which are the critical players and the dominant primary colonisers and net
producers during the melt season. Here for the first time we have evaluated the
role of these algae in association with the full microbial community composition
(i.e., algae, bacteria, archaea) in distinct surface habitats and on 12 glaciers
and permanent snow fields in Svalbard and Arctic Sweden. We cross-correlated
these data with the analyses of specific metabolites such as fatty acids and
pigments, and a full suite of potential critical physico-chemical parameters
including major and minor nutrients, and trace metals. It has been shown that
correlations between single algal species, metabolites, and specific geochemical
parameters can be used to unravel mixed metabolic signals in complex communities,
further assign them to single species and infer their functionality. The data
also clearly show that the production of metabolites in snow and ice algae is
driven mainly by nitrogen and less so by phosphorus limitation. This is
especially important for the synthesis of secondary carotenoids, which cause a
darkening of glacial surfaces leading to a decrease in surface albedo and
eventually higher melting rates.
PMID- 27511456
TI - Quantification of intact plasma AGT consisting of oxidized and reduced
conformations using a modified ELISA.
AB - The pleiotropic actions of the renin-angiotensin system (RAS) depend on the
availability of angiotensinogen (AGT) which generates angiotensin I (ANG I) when
cleaved by renin. Thus, quantification of the intact AGT (iAGT) concentrations is
important to evaluate the actual renin substrate available. The iAGT conformation
exists as oxidized AGT (oxi-AGT) and reduced AGT (red-AGT) in a disulfide bond,
and oxi-AGT has a higher affinity for renin, which may exacerbate RAS-associated
diseases. Accordingly, we determined iAGT, oxi-AGT, and red-AGT levels in plasma
from rats and mice. Blood samples were obtained by cardiac puncture and then
immediately mixed with an inhibitor solution containing a renin inhibitor. Total
AGT (tAGT) levels were measured by tAGT ELISA which detects both cleaved and
iAGT. iAGT levels were determined by iAGT ELISA which was found to only detect
red-AGT. Thus, it was necessary to treat samples with dithiothreitol, a reducing
agent, to quantify total iAGT concentration. tAGT levels in rat and mouse plasma
were 1,839 +/- 139 and 1,082 +/- 77 ng/ml, respectively. iAGT levels were 53% of
tAGT in rat plasma but only 22% in mouse plasma, probably reflecting the greater
plasma renin activity in mice. The ratios of oxi-AGT and red-AGT were ~4:1 (rat)
and 16:1 (mouse). Plasma iAGT consists of oxi-AGT and red-AGT, suggesting that
oxidative stress can influence ANG I generation by the AGT conformation switch.
Furthermore, the lower availability of plasma iAGT in mice suggests that it may
serve as a limiting factor in ANG I formation in this species.
PMID- 27511458
TI - WUWHS 2016: What Promises for the Future?
PMID- 27511457
TI - An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the
progression of diabetic kidney disease.
AB - While angiotensin II blockade slows the progression of diabetic nephropathy,
current data suggest that it alone cannot stop the disease process. New therapies
or drug combinations will be required to further slow or halt disease
progression. Inhibition of plasminogen activator inhibitor type 1 (PAI-1) aimed
at enhancing ECM degradation has shown therapeutic potential in diabetic
nephropathy. Here, using a mouse model of type diabetes, the maximally
therapeutic dose of the PAI-1-neutralizing mouse monoclonal antibody (MEDI-579)
was determined and compared with the maximally effective dose of enalapril. We
then examined whether addition of MEDI-579 to enalapril would enhance the
efficacy in slowing the progression of diabetic nephropathy. Untreated
uninephrectomized diabetic db/db mice developed progressive albuminuria and
glomerulosclerosis associated with increased expression of transforming growth
factor (TGF)-beta1, PAI-1, type IV collagen, and fibronectin from weeks 18 to 22,
which were reduced by MEDI-579 at 3 mg/kg body wt, similar to enalapril given
alone from weeks 12 to 22 Adding MEDI-579 to enalapril from weeks 18 to 22
resulted in further reduction in albuminuria and markers of renal fibrosis. Renal
plasmin generation was dramatically reduced by 57% in diabetic mice, a decrease
that was partially reversed by MEDI-579 or enalapril given alone but was further
restored by these two treatments given in combination. Our results suggest that
MEDI-579 is effective in slowing the progression of diabetic nephropathy in db/db
mice and that the effect is additive to ACEI. While enalapril is renal
protective, the add-on PAI-1 antibody may offer additional renoprotection in
progressive diabetic nephropathy via enhancing ECM turnover.
PMID- 27511460
TI - Endothelial Transcytosis of Insulin: Does It Contribute to Insulin Resistance?
AB - Most research on insulin resistance has focused on impaired signaling at the
level of target tissues like skeletal muscle. Insulin delivery is also important
and includes recruitment and perfusion of capillaries bearing insulin, but also
the transit of insulin across the capillary endothelium. The mechanisms of this
second stage (insulin transcytosis) and whether it contributes to insulin
resistance remain uncertain.
PMID- 27511459
TI - Gut Microbiota: Modulation of Host Physiology in Obesity.
AB - Many factors are involved in weight gain and metabolic disturbances associated
with obesity. The gut microbiota has been of particular interest in recent years,
since both human and animal studies have increased our understanding of the
delicate symbiosis between the trillions of microbes that reside in the GI tract
and the host. It has been suggested that disruption of this mutual tolerance may
play a significant role in modulating host physiology during obesity.
Environmental influences such as diet, exercise, and early life exposures can
significantly impact the composition of the microbiota, and this dysbiosis can in
turn lead to increased host adiposity via a number of different mechanisms. The
ability of the microbiota to regulate host fat deposition, metabolism, and immune
function makes it an attractive target for achieving sustained weight loss.
PMID- 27511461
TI - Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function.
AB - Cells in the body are exposed to irregular mechanical stimuli. Here, we review
the so-called fluctuation-driven mechanotransduction in which stresses stretching
cells vary on a cycle-by-cycle basis. We argue that such mechanotransduction is
an emergent network phenomenon and offer several potential mechanisms of how it
regulates cell function. Several examples from the vasculature, the lung, and
tissue engineering are discussed. We conclude with a list of important open
questions.
PMID- 27511463
TI - Negative News: Cl- and HCO3- in the Vascular Wall.
AB - Cl(-) and HCO3 (-) are the most prevalent membrane-permeable anions in the intra-
and extracellular spaces of the vascular wall. Outwardly directed electrochemical
gradients for Cl(-) and HCO3 (-) permit anion channel opening to depolarize
vascular smooth muscle and endothelial cells. Transporters and channels for Cl(-)
and HCO3 (-) also modify vascular contractility and structure independently of
membrane potential. Transport of HCO3 (-) regulates intracellular pH and thereby
modifies the activity of enzymes, ion channels, and receptors. There is also
evidence that Cl(-) and HCO3 (-) transport proteins affect gene expression and
protein trafficking. Considering the extensive implications of Cl(-) and HCO3 (-)
in the vascular wall, it is critical to understand how these ions are transported
under physiological conditions and how disturbances in their transport can
contribute to disease development. Recently, sensing mechanisms for Cl(-) and
HCO3 (-) have been identified in the vascular wall where they modify ion
transport and vasomotor function, for instance, during metabolic disturbances.
This review discusses current evidence that transport (e.g., via NKCC1, NBCn1,
Ca(2+)-activated Cl(-) channels, volume-regulated anion channels, and CFTR) and
sensing (e.g., via WNK and RPTPgamma) of Cl(-) and HCO3 (-) influence
cardiovascular health and disease.
PMID- 27511462
TI - Ion Channels in Endothelial Responses to Fluid Shear Stress.
AB - Fluid shear stress is an important environmental cue that governs vascular
physiology and pathology, but the molecular mechanisms that mediate endothelial
responses to flow are only partially understood. Gating of ion channels by flow
is one mechanism that may underlie many of the known responses. Here, we review
the literature on endothelial ion channels whose activity is modulated by flow
with an eye toward identifying important questions for future research.
PMID- 27511464
TI - Clinical validation of a precision electromagnetic tremor measurement system in
participants receiving deep brain stimulation for essential tremor.
AB - Tremor is characterized commonly through subjective clinical rating scales.
Accelerometer-based techniques for objective tremor measurement have been
developed in the past, yet these measures are usually presented as an unintuitive
dimensionless index without measurement units. Here we have developed a tool
(TREMBAL) to provide quantifiable and objective measures of tremor severity using
electromagnetic motion tracking. We aimed to compare TREMBAL's objective measures
with clinical tremor ratings and determine the test-retest reliability of our
technique. Eight participants with ET receiving deep brain stimulation (DBS)
therapy were consented. Tremor was simultaneously recorded using TREMBAL and
video during DBS adjustment. After each adjustment, participants performed a
hands-outstretched task (for postural tremor) and a finger-nose task (for kinetic
tremor). Video recordings were de-identified, randomized, and shown to a panel of
movement disorder specialists to obtain their ratings. Regression analysis and
Pearson's correlations were used to determine agreement between datasets. Subsets
of the trial were repeated to assess test-retest reliability. Tremor amplitude
and velocity measures were in close agreement with mean clinical ratings (r >
0.90) for both postural and kinetic tremors. Test-retest reliability for both
translational and rotational components of tremor showed intra-class correlations
>0.80. TREMBAL assessments showed that tremor gradually improved with increasing
DBS therapy-this was also supported by clinical observation. TREMBAL measurements
are a sensitive, objective and reliable assessment of tremor severity. This tool
may have application in clinical trials and in aiding automated optimization of
deep brain stimulation.
PMID- 27511465
TI - Divergent habitat filtering of root and soil fungal communities in temperate
beech forests.
AB - Distance decay, the general reduction in similarity of community composition with
increasing geographical distance, is known as predictor of spatial variation and
distribution patterns of organisms. However, changes in fungal communities along
environmental gradients are little known. Here we show that distance decays of
soil-inhabiting and root-associated fungal assemblages differ, and identify
explanatory environmental variables. High-throughput sequencing analysis of
fungal communities of beech-dominated forests at three study sites across Germany
shows that root-associated fungi are recruited from the soil fungal community.
However, distance decay is substantially weaker in the root-associated than in
the soil community. Variance partitioning of factors contributing to the observed
distance decay patterns support the hypothesis that host trees stabilize the
composition of root-associated fungi communities, relative to soil communities.
Thus, they not only have selective impacts on associated communities, but also
buffer effects of changes in microclimatic and environmental variables that
directly influence fungal community composition.
PMID- 27511466
TI - Assessment of the mean time in the therapeutic INR range and the SAME-TT2R2 score
in patients with atrial fibrillation and cognitive impairment.
AB - INTRODUCTION Most patients with atrial fibrillation (AF) are elderly and may
have an increased risk of cognitive disorders. Low mean values of the therapeutic
international normalized ratio (INR) range (TTR) (<=60%) are associated with
increased risk of stroke, vascular events, and bleeding complications. OBJECTIVES
The aim of the study was to evaluate the efficacy of long-term anticoagulant
therapy in patients treated with vitamin K antagonists (VKAs), depending on their
cognitive functions. In addition, we used the SAMe-TT2R2 risk score to predict
the risk of ineffective anticoagulation. PATIENTS AND METHODS The analysis
comprised 154 patients (68 men and 86 women; mean age, 76 +/-10 years) with AF
and indications for long-term therapy with VKA (CHA2DS2-VASc score >=1, HAS-BLED
score <3). Cognitive functions were evaluated using the Mini-Mental State
Examination (MMSE) score. The efficacy of VKA therapy was determined by the TTR
values from the preceding 6 months of treatment. We used the SAMe-TT2R2 score to
identify patients who were likely to have poor INR control. RESULTS Depending
on the number of MMSE points, patients treated with VKAs were divided into 2
groups: patients with normal cognitive functions (MMSE score >=27; n = 62) and
those with cognitive impairment (MMSE score <27; n = 42). Despite the fact that
all patients had indications for anticoagulant therapy, 50 patients (32%)
received no VKAs on admission. The mean TTR value exceeded 60% in 61% of patients
with an MMSE score of 27 points or higher, whereas mean TTR value was 28% in
patients with an MMSE score of less than 27 (P <0.0001). Patients with a SAMe
TT2R2 score of 0 to 1 had higher TTR values than those with a SAMe-TT2R2 score of
2 or higher (r = -0.24; P <0.05 ). The cognitive status was significantly more
impaired in patients with persistent and permanent AF compared with patients with
paroxysmal AF (MMSE score, 25.8 +/-3.7 vs 28.6 +/-2; P <0.0001). CONCLUSIONS
Cognitive disorders in patients with AF significantly reduce the efficacy of VKA
therapy. The decision to administer VKA treatment should be based not only on the
CHA2DS2-VASc and HAS-BLED scores, but also on the SAMe-TT2R2 score and the
evaluation of the patient's cognitive functions.
PMID- 27511467
TI - Extra-articular tenodesis combined with an anterior cruciate ligament
reconstruction in acute anterior cruciate ligament tear in elite female football
players.
AB - PURPOSE: The growing popularity of elite soccer among female participants has led
to increased incidents of anterior cruciate ligament (ACL) ruptures. Many authors
underline a positive glide after ACL reconstruction (ACLR), especially in women.
In fact, an isolated intra-articular ACLR may be inadequate to control rotational
instability after a combined injury of the ACL and the peripheral structures of
the knee. Extra-articular procedures are sometimes used in primary cases
displaying excessive antero-lateral rotatory instability. The purpose of this
case series was to report subjective and objective outcomes after combined ACL
and lateral extra-articular tenodesis (LET) with a minimum 4-year follow-up in a
selected high-risk population of elite female football players. METHODS: Between
January 2007 and December 2010, 16 elite Italian female football players were
included in the study. All patients underwent the same surgical technique:
anatomical ACLR with autogenous semitendinosus and gracilis tendons. After the
intra-articular reconstruction was performed, an additional extra-articular
MacIntosh modified Coker-Arnold procedure was carried out. Patients were assessed
pre- and post-operatively with the subjective and objective International Knee
Documentation Committee (IKDC) evaluation form, Tegner activity scale (TAS) and
Lysholm score. Joint laxity was assessed with KT-1000 by measuring the side-to
side (S/S) differences in displacement at manual maximum (mm) testing. RESULTS:
At a mean follow-up of 72.6 +/- 8.1 months, two independent examiners reviewed
all players. All of the patients had a fully recovered range of motion. Lachman
test was negative in all patients (100 %). The evaluation of joint laxity and
clinical evaluation showed a statistically significant improvement. No patients
experienced complication or a re-rupture. DISCUSSION: The rationale of combining
extra-articular procedures with ACLR is to restrict the internal rotation of the
reconstructed knee, taking advantage of its long lever arm and thus providing
more stability in the rotational axis and preventing the ACL graft from
undergoing further excessive strain. CONCLUSIONS: The combination of an LET with
ACLR in elite female football players demonstrated excellent results in terms of
subjective scales, post-operative residual laxity and re-rupture rate with no
complication, and a complete return to sport activity.
PMID- 27511468
TI - Persistent non-union of the humeral shaft treated by plating and autologous bone
grafting.
AB - INTRODUCTION: Surgical treatment of persistent non-union of the humeral shaft is
a complex situation because of the risk of failure and surgery-related
complications. The primary objective of this study was to evaluate clinical and
radiological results of a continuous series of persistent non-union treated with
plating and bone grafting. The secondary objective was to expose factors
contributing to the failure of prior bone union attempts. MATERIAL AND METHODS:
Sixteen patients (average age of 52 years) were treated for persistent non-union
of the humeral shaft in our department; six of these patients had predisposing
comorbidities or addictions. The persistent non-union was treated by plating with
autologous bone graft from the iliac crest in a single-stage procedure in 12
cases and a two-stage procedure in three cases; one case was treated with plating
and vascularized fibula graft. RESULTS: At a minimum follow-up of 12 months
(average 78 months), four (25 %) failed to heal. The 12 other patients had bone
union after an average of eight months. The average QuickDASH score was 48 points
(18-72). A retrospective analysis of the prior attempts to treat the non-union
revealed three cases of unstable fixation, four cases with no osteogenic supply
and seven cases of positive microbiological cultures at the non-union site.
CONCLUSION: Plating and autologous bone grafting resulted in union in only 75 %
of persistent non-union of the humeral shaft. The persistent nature of the
humeral shaft non-union could be attributed to deviating from validated rules for
surgical treatment and/or the presence of a surgical site infection.
PMID- 27511469
TI - Variations in the obturator artery around the obturator foramen assessed by three
dimensional computed tomographic angiography and prevention of vascular-related
complications in rotational acetabular osteotomy.
AB - PURPOSE: The aims of this study were (1) to evaluate the anatomical variations
and locations of the obturator artery at the obturator foramen using computed
tomographic (CT) angiography images and (2) to evaluate the pubic osteotomy site
in rotational acetabular osteotomy using postoperative CT images in order to
assess the relationship between the obturator artery and the pubic osteotomy
site. METHODS: We examined a total of 196 hips in 98 consecutive Japanese
patients for aim (1), and 38 consecutive patients who underwent rotational
acetabular osteotomy for aim (2). RESULTS: The prevalence of arterial anastomosis
of the obturator artery (corona mortis) was 14.3 %, with the obturator artery
being located closer to the superior pubic ramus and the osteotomy site in these
subjects. CONCLUSIONS: Extensive care should be taken during rotational
acetabular osteotomy in patients showing variations of the obturator artery with
corona mortis.
PMID- 27511470
TI - Comparison of open reduction and internal fixation and primary total hip
replacement for osteoporotic acetabular fractures: a retrospective clinical
study.
AB - PURPOSE: Treating acetabular fractures with open reduction and internal fixation
(ORIF) may lead to poorer outcomes in older patients. As data for osteoporotic
acetabular fractures are limited, we compared primary total hip replacement (THR)
with ORIF for treating osteoporotic acetabular fractures, including those with
posterior column instability. METHODS: All patients with osteoporotic acetabular
fractures, treated with ORIF or primary THR from 2005 to 2015, were assessed
retrospectively for clinical and radiologic outcomes. Indication criteria for
selecting primary THR were evaluated. RESULTS: Twenty-three patients were treated
with ORIF and nine with primary THR (performed with an anti-protrusion cage). If
the posterior column was unstable, THR was combined with posterior column bridge
plating. Indications for THR were the presence of a comminuted fracture pattern,
approach-related risk factors for ORIF, and mobilization issues. Biomechanical
reconstruction was acceptable with THR. Acetabular component loosening was
observed only once. Secondary THR was indicated in 45 % of the ORIF cases.
DISCUSSION: ORIF for acetabular fracture in older patients is unsatisfactory and
may be even worse for osteoporotic fractures. Immobilization for long-term
restricted weight bearing after ORIF is hazardous. Primary THR may enable early
post-operative full weight-bearing. Various techniques, affording fixation of the
unstable acetabular columns, are described. In THR with an anti-protrusion cage,
only dorsal column instability needs to be addressed. CONCLUSION: The described
technique achieved sufficient acetabular component stability. Primary THR with an
anti-protrusion cage is an advantageous option to ORIF and should be strongly
considered for osteoporotic acetabular fractures.
PMID- 27511472
TI - Automated lesion annotation during pulmonary vein isolation: influence on acute
isolation rates and lesion characteristics.
AB - PURPOSE: Recovery of pulmonary vein (PV) conduction is a common mechanism of
atrial fibrillation recurrence after PV isolation (PVI), underscoring the need
for durable lesion formation. We aimed to evaluate the utility of an automated
lesion annotation algorithm (ALAA) on acute isolation rates and resulting lesion
characteristics. METHODS: Fifty patients underwent PVI using a contact force (CF)
sensing catheter and ALAA. Single antral circles around ipsilateral PVs were
performed with ALAA-1 settings including catheter stability (range of motion <=2
mm, duration >10 s). Target CF was 10-20 g but not part of ALAA-1 settings. If PV
conduction persisted after circle completion, force over time was added to
automated settings (ALAA-2). Emerging gaps were subsequently ablated, followed by
re-assessment for PVI. RESULTS: ALAA-1 isolated 70 % of the left and 78 % of the
right PVs using 756.3 +/- 212.3 s (left) and 737.1 +/- 145.9 s (right) of energy
delivery. ALAA-2 settings identified 29 gaps in previously unisolated PVs,
closure significantly increased isolation rates to 88 % of the left and 96 % of
the right PVs with additional 325.4 +/- 354.1 s (left) and 266.8 +/- 279.5 s
(right) of energy delivery (p = 0.001). Lesion characteristics significantly
differed between ALAA-1 (n = 3521 lesions) and ALAA-2 (n = 3037 lesions)
settings, and between isolated and non-isolated PV segments, particularly with
respect to CF. Interlesion distances with ALAA-2 were significantly longer in the
left superior, left superior-anterior, and right superior-posterior segments when
compared to ALAA-1. CONCLUSIONS: Settings of an ALAA affect lesion
characteristics reveal areas of insufficient lesion formation and influence acute
effectiveness of PVI. Combination of CF and stability shows superior performance
over stability alone.
PMID- 27511471
TI - Oral sensory nerve damage: Causes and consequences.
AB - Oral sensations (i.e., taste, oral somatosensation, retronasal olfaction) are
integrated into a composite sense of flavor, which guides dietary choices with
long-term health impact. The nerves carrying this input are vulnerable to
peripheral damage from multiple sources (e.g., otitis media, tonsillectomy, head
injury), and this regional damage can boost sensations elsewhere in the mouth
because of central interactions among nerve targets. Mutual inhibition governs
this compensatory process, but individual differences lead to variation in whole
mouth outcomes: some individuals are unaffected, others experience severe loss,
and some encounter sensory increases that may (if experienced early in life)
elevate sweet-fat palatability and body mass. Phantom taste, touch, or pain
sensations (e.g., burning mouth syndrome) may also occur, particularly in those
expressing the most taste buds. To identify and treat these conditions
effectively, emerging clinical tests measure regional vs. whole-mouth sensation,
stimulated vs. phantom cues, and oral anatomy. Scaling methods allowing valid
group comparisons have strongly aided these efforts. Overall, advances in
measuring oral sensory function in health and disease show promise for
understanding the varied clinical consequences of nerve damage.
PMID- 27511473
TI - Fraction of exhaled nitric oxide as a predictor in juvenile idiopathic arthritis
progression.
AB - In this study, the relation between the nitric oxide (NO) levels in the serum and
fraction of exhaled nitric oxide (FENO) in children with juvenile idiopathic
arthritis (JIA) and the activation criteria of the disease has been investigated.
The study group consisted of 35 JIA-diagnosed patients and 18 healthy children.
According to the clinical and laboratory findings, the patients with JIA were
divided into two groups, active (group I) and in remission (group II). The
healthy children were classified as group III. The activation criteria of the
disease were determined for each patient. The serum NO level and FENO level were
measured in all the patients. In the group with JIA, correlation was detected
between FENO level and number of involved joints and number of joints with
limited motion. In addition, correlation was determined between the FENO level
and number of involved joints in group I and the serum NO level and activity
score in group II. However, it was seen that there is no statistical difference
in the serum NO level and FENO level of the patients with JIA and the control
group and groups I and II. This study demonstrated the correlation between FENO
level and number of involved joints and number of joints with limited motion in
patients with JIA. Our results matter in terms of FENO being a noninvasive
laboratory marker in following the progression of the disease.
PMID- 27511474
TI - Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)
Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic
Structures.
AB - Cobalt(II)-based metalloradical catalysis (MRC) has been successfully applied for
effective construction of the highly strained 2-sulfonyl-1,3
diazabicyclo[3.1.0]hexane structures in high yields through intramolecular
radical aziridination of allylic sulfamoyl azides. The resulting [3.1.0] bicyclic
aziridines prove to be versatile synthons for the preparation of a diverse range
of 1,2- and 1,3-diamine derivatives by selective ring-opening reactions. As a
demonstration of its application for target synthesis, the metalloradical
intramolecular aziridination reaction has been incorporated as a key step for
efficient synthesis of a potent neurokinin 1 (NK1 ) antagonist in 60 % overall
yield.
PMID- 27511475
TI - Dietary sodium and nocturnal blood pressure dipping in normotensive men and
women.
AB - Impaired nocturnal blood pressure (BP) dipping (i.e., <10% decline in nocturnal
BP) is associated with an increased risk of cerebrovascular and cardiovascular
diseases. Excess sodium has been shown to impair BP regulation and increase
cardiovascular disease risk, yet few studies have assessed the influence of
dietary sodium on nocturnal dipping in normotensive adults. The purpose of this
study was to determine the effects of dietary sodium on BP dipping in
normotensive men and women. Eighty healthy normotensive adults participated in a
controlled feeding study (men: n=39, 34+/-2 years; women: n=41, 41+/-2 years).
Participants consumed a standardized run-in 100 mmol sodium per day diet for 7
days, followed by 7 days of low-sodium (LS; 20 mmol per day) and high-sodium (HS;
300 mmol per day) diets in random order. On the final day of each diet, subjects
wore a 24 h ambulatory BP monitor, collected a 24 h urine sample and provided a
blood sample. During the run-in diet, 24 h urinary sodium excretion was 79.4+/
5.1 mmol per 24 h in men and 85.3+/-5.5 mmol per 24 h in women (P>0.05). Systolic
BP dipping was not different between men (11.4+/-1.0%) and women (11.2+/-0.9%);
(P>0.05). During the HS diet, 24 h urinary sodium excretion increased compared
with the LS diet in men (LS=31.7+/-4.6 mmol per 24 h vs HS=235.0+/-13.9 mmol per
24 h, P<0.01) and women (LS=25.8+/-2.2 mmol per 24 h vs HS=234.7+/-13.8 mmol per
24 h, P<0.01). Despite this large increase in sodium intake and excretion,
systolic BP dipping was not blunted in men (LS=8.9+/-1.0% vs HS=9.4+/-1.2%,
P>0.05) or women (LS=10.3+/-0.8% vs HS=10.5+/-0.8%, P>0.05). Among normotensive
men and women, HS does not blunt nocturnal BP dipping.
PMID- 27511476
TI - Blood pressure-lowering effects of nifedipine/candesartan combinations in high
risk individuals: subgroup analysis of the DISTINCT randomised trial.
AB - The DISTINCT study (reDefining Intervention with Studies Testing Innovative
Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of
nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies
and placebo in patients with hypertension. This descriptive sub-analysis examined
blood pressure (BP)-lowering effects in high-risk participants, including those
with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422),
type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and
cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age
and body mass index (BMI). Participants with grade I/II hypertension were
randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan
cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and
diastolic BP reductions after treatment in high-risk participants were greater,
overall, with N/C combinations vs respective monotherapies or placebo, with
indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013
guideline criteria) were also achieved with highest doses of N/C combinations in
each high-risk subgroup. The benefits of combination therapy vs monotherapy were
additionally observed in patient subgroups categorised by gender, age or BMI. All
high-risk participants reported fewer vasodilatory adverse events in the pooled
N/C combination therapy than the N monotherapy group. In conclusion, consistent
with the DISTINCT main study outcomes, high-risk participants showed greater
reductions in BP and higher control rates with N/C combinations compared with
respective monotherapies and lesser vasodilatory side-effects compared with N
monotherapy.
PMID- 27511477
TI - Association between sleep disorders and hypertension in Taiwan: a nationwide
population-based retrospective cohort study.
AB - There is insufficient evidence to assess the risk for hypertension in patients
with sleep disorders (SDs) in a large population-based cohort study. The aim of
this study was to examine the risk of hypertension in groups both with and
without SDs. Taiwan's National Health Insurance Research Database (NHIRD) data
from 2005 to 2010 were used in a retrospective cohort study. A Cox proportional
hazard regression analysis was used to evaluate the effects of SDs on
hypertension risk. The overall incidence of hypertension was 120.7 per 1000
person-years for patients with SDs, which was significantly higher than that of
the non-SD comparison cohort (76.4 per 1000 person-years). Overall, patients with
SDs had a higher risk of hypertension compared with comparison cohort (adjusted
hazard ratio (HR)=1.58, 95% confidence interval (CI)=1.26-1.79). Among patients
aged <40 years, patients with SDs had a higher risk for hypertension than the
comparison cohort (adjusted HR, 2.90 (95% CI, 2.46-3.14)). Compared with the
cohort without insomnia, patients with insomnia had a 21% higher risk for
hypertension (adjusted HR, 1.21 (95% CI, 1.01-1.76)). Compared with non-SD
comparison cohort, patients with SDs had a higher risk for developing
hypertension, particularly pronounced among those who were younger adults (age
?40 years) and who had insomnia. We suggest that possible persisting exposure to
sleep problems was correlated with a greater risk of hypertension.
PMID- 27511479
TI - Initial experience with delivery of palliative care toterminal cancer patients.
AB - BACKGROUND/AIM: We investigated the symptoms and needs of terminal cancer
patients in a region where formal palliative care is limited. Here we present the
demographic features and symptoms of end-stage cancer patients living in a city
in northern Turkey. MATERIALS AND METHODS: The study was conducted at
Gaziosmanpasa University (Tokat, Turkey), in 2011 and 2012. End-stage cancer
patients admitted or referred by various departments to our outpatient pain unit
were included. Demographic data, treatment histories, primary tumor sites,
patient complaints, and symptom intensities measured using the Edmonton Symptom
Assessment System Scale were prospectively entered into a database. RESULTS: A
total of 107 patients (36 female and 71 male) were included. Gastrointestinal
cancer was the most common form of cancer (43%), followed by genitourinary
(25.3%) and lung cancer (15%). The most common symptom was fatigue (98.1%). The
other symptoms (in decreasing order) were pain (92.5%), insomnia (92.5%), loss of
appetite (76.6%), constipation (71%), dyspnea (63.6%), nausea (60.7%), cough
(57.9%), and vomiting (48.6%). Eighty-six percent of the patients (n = 92) had
metastases. Most lived in the city (59.8%) and 84 (78.5%) lived with their
spouses. CONCLUSION: Patients were referred at the late stages of disease with
pain as the principal presenting symptom. Family members were the principal
caregivers.
PMID- 27511480
TI - Depression, anxiety, and their relation with clinical parametersand androgen
levels in hirsute women.
AB - BACKGROUND/AIM: The purpose of this study was to assess the prevalence of anxiety
and depression among patients with hirsutism and to evaluate the relationships of
anxiety and depression with clinical parameters and androgen levels. MATERIALS
AND METHODS: One hundred and seven women with hirsutism were enrolled in the
study. All participants completed standardized questionnaires to assess
depression (Beck Depression Inventory (BDI)) and anxiety (Beck Anxiety Inventory
(BAI)). The Ferriman-Gallwey (FG) scores, body mass indexes (BMIs), homeostatic
model assessments of insulin resistance (HOMA-IR), and serum androgen levels of
all patients were obtained. RESULTS: Seventy-four of the 107 patients (69.15%)
had BDI scores indicating depression, and 47 of the 107 patients (43.9%) had BAI
scores indicating anxiety disorders. No difference was found between high BAI and
normal BAI patients related to BMI, age, FG scores, testosterone levels, and HOMA
IR levels (P > 0.05), and no difference was found between high BDI and normal BDI
patients related to BMI, age, FG scores, free testosterone levels, and HOMA-IR
levels. There was a positive correlation between BDI scores and
dehydroepiandrosterone sulphate (DHEA-S) levels (P < 0.01). CONCLUSION: We found
considerable amounts of depression, anxiety, and the coexistence of depression
and anxiety in patients with hirsutism. Depression and the severity of depressive
symptoms were positively correlated with DHEA-S levels.
PMID- 27511478
TI - High-dose calcium channel blocker (CCB) monotherapy vs combination therapy of
standard-dose CCBs and angiotensin receptor blockers for hypertension: a meta
analysis.
AB - In this study, we evaluated the efficacy and safety of high-dose calcium channel
blocker (CCB) monotherapy and standard-dose CCBs combined with angiotensin
receptor blockers (ARBs) for patients with hypertension. A comprehensive search
of PubMed, Embase and the Cochrane Central Register of Controlled Trials was
performed in December 2015. Randomized controlled trials designed to identify the
above goal were included. Thirteen trials including 2371 patients were
identified. The standard-dose CCB/ARB combination resulted in a greater reduction
of systolic blood pressure (WMD -2.52, 95% confidence interval (CI): -3.76 to
1.28) and diastolic blood pressure (weighted mean difference (WMD) -2.07, 95% CI:
-3.73 to -0.42) compared to high-dose CCB monotherapy. The overall hypertension
control rate for the CCB/ARB combination was higher than that for CCB monotherapy
(relative risk (RR): 1.17, 95% CI: 1.08-1.26). Furthermore, the CCB/ARB
combination treatment yielded significantly fewer overall adverse events (RR:
0.84, 95% CI: 0.74-0.95), oedema (RR: 0.31; 95% CI: 0.18-0.52) and rash (RR:
0.27, 95% CI: 0.08-0.96, P=0.04) than did CCB monotherapy. The standard-dose
CCB/ARB combination is superior to high-dose CCB monotherapy for lowering blood
pressure and reducing adverse events in hypertensive patients. Future research
should focus on the cost-effectiveness and long-term effects of these two
treatment strategies for patients with hypertension.
PMID- 27511481
TI - The relationship of mean platelet volume with microalbuminuriain type 2 diabetic
patients.
AB - BACKGROUND/AIM: Activation and size of platelets have been suggested to be
involved in the pathogenesis of vascular complications in diabetes mellitus. The
purpose of the present study was to investigate the association of mean platelet
volume with microalbuminuria in type 2 diabetic patients. MATERIALS AND METHODS:
Mean platelet volume levels were investigated in healthy participants and type 2
diabetic patients with and without microalbuminuria. After their mean platelet
volume values were compared, correlation of mean platelet volume with sex,
duration of diabetes, microalbuminuria, fasting blood glucose, hemoglobin A1c,
creatinine clearance, and body mass index was examined. RESULTS: Mean platelet
volume levels were higher in all diabetic patients than those in controls. Mean
platelet volume levels were highest in diabetics with microalbuminuria. The mean
platelet volume levels had a positive correlation with microalbuminuria.
CONCLUSION: Mean platelet volume values of diabetic patients were higher than
those of nondiabetics, the highest levels being in diabetics with
microalbuminuria. Our results suggest that microalbuminuria might be related with
mean platelet volume in diabetic patients.
PMID- 27511482
TI - Total white blood cell count, liver enzymes, and metabolic syndrome in
schizophrenia.
AB - BACKGROUND/AIM: Metabolic syndrome (MetS) is an important clinical issue in
patients with schizophrenia, but its associated factors are still ambiguous. The
aim of the present study was to test whether there are any associations between
MetS and white blood cell (WBC) levels, liver enzymes, or sociodemographic
variables. MATERIALS AND METHODS: The study included 91 patients with a diagnosis
of schizophrenia. We used the National Cholesterol Education Program's Third
Adult Treatment Protocol criteria to evaluate MetS in patients. Schizophrenia
patients with MetS were compared with those without MetS on the basis of
demographic and clinical characteristics and total WBC counts. We conducted
Spearman's correlation and binary logistic regression analyses to achieve the
best prediction of MetS in schizophrenia. RESULTS: Compared with schizophrenia
patients without MetS, those with MetS were older, less educated, and more likely
to be smokers. They were also more likely to have a longer duration of the
illness, a longer untreated period, and higher alanine aminotransferase (ALT) and
WBC levels. MetS was correlated with age, duration of illness, income, ALT, gamma
glutamyl transpeptidase, WBC, and hemoglobin values. Age and WBC levels were
found to be the best predictors of MetS. CONCLUSION: Hemograms and liver tests
should be conducted to test for MetS in schizophrenia.
PMID- 27511483
TI - The effect of hip and knee exercises on pain, function, and strength in
patientswith patellofemoral pain syndrome: a randomized controlled trial.
AB - BACKGROUND/AIM: The role of hip muscles in the rehabilitation of patellofemoral
pain syndrome has recently received interest. The aim of this study was to
compare the efficiencies of hip exercises alongside knee exercises versus only
knee exercises on pain, function, and isokinetic muscle strength in patients with
this syndrome. MATERIALS AND METHODS: Fifty-five young female patients (mean age:
34.1 +/- 6.2 years; mean BMI: 25.9 +/- 3.9 kg/m2) with patellofemoral pain
syndrome were included. The patients were randomized into groups of hip-and-knee
exercises and knee-only exercise programs for 6 weeks with a total of 30 sessions
at the clinic. Both groups were evaluated before therapy, after 6 weeks of a
supervised exercise program, and after 6 weeks of an at-home exercise program.
The outcome measures were muscle strength, pain, and both subjective and
objective function. RESULTS: The improvements of the patients in the hip-and-knee
exercise group were better than in patients of the knee-only exercise group in
terms of scores of pain relief (P < 0.001) and functional gain (P = 0.002) after
12 weeks. CONCLUSION: We suggest additional hip-strengthening exercises to
patients with patellofemoral pain syndrome in order to decrease pain and increase
functional status.
PMID- 27511484
TI - Sensitization to food and inhalant allergens in healthy children in Van, East
Turkey.
AB - BACKGROUND/AIM: The purpose of this study was to determine the most frequent food
and inhalant allergens leading to allergic sensitization in children in Van
Province of Turkey. MATERIALS AND METHODS: The study included 1052 serum samples
with no diagnosis of allergy. The sera were tested with the Euroline Pediatric
IgE test kit (EUROIMMUN, Germany). By using the EUROLineScan digital evaluation
system, the intensity of bands was calculated with enzyme allergosorbent test
classification. RESULTS: Out of the 1052 tested sera, 143 were found to be cross
reactive carbohydrate determinant-positive and were discarded from the study. Of
the remaining 909 sera, 513 (56%) were from males and 296 (44%) were from
females. Among the food allergens, specific IgE was most frequently found against
codfish, potato, cow's milk, egg yolk, egg white, and rice, and among the
inhalant allergens against cats, dogs, grass mix, Dermatophagoides pteronyssinus,
and Aspergillus fumigatus, respectively. CONCLUSION: The finding of codfish being
the most frequent allergen was related to the high consumption of trout in the
region and endemicity of pearl mullet in Lake Van. The results obtained could
contribute to determining the etiology of allergic diseases. Additionally,
regular analysis of changes in allergen sensitization is important for prevention
of allergic disease.
PMID- 27511485
TI - How to close open choledochotomy: primary closure, primary closurewith T-tube
drainage, or choledochoduodenostomy?
AB - BACKGROUND/AIM: Although common bile duct stones are generally treated
endoscopically, surgery is required if endoscopic removal is impossible. The aim
of this study was to compare the surgical options in such patients. MATERIALS AND
METHODS: A total of 282 patients with common bile duct stones underwent open
choledochotomy; primary closure was applied in 48 (17.0%), primary closure with T
tube drainage in 81 (28.7%), and choledochoduodenostomy in 153 (54.3%) patients.
RESULTS: Postoperative complications were seen in 8 (16.7%) patients in the
primary closure, 33 (40.7%) patients in the primary closure with T-drainage, and
37 (24.2%) patients in the choledochoduodenostomy group. No significant
differences were observed among the groups (P > 0.05). The mean postoperative
hospital stays in the primary closure, primary closure with T-tube drainage, and
choledochoduodenostomy groups were 5.5, 13.5, and 8.9 days, respectively. The
mean postoperative hospitalization was significantly shorter in the primary
closure group than in the other groups (P < 0.05). CONCLUSION: Primary closure is
a safe and feasible method in selected patients.
PMID- 27511486
TI - Comparison of nasal senses following open and closed rhinoplasty.
AB - BACKGROUND/AIM: The objective of this study was to compare the postoperative
changes taking place in the nasal senses of patients who underwent a rhinoplasty
through the open or closed incision method. MATERIALS AND METHODS: In a
prospective study, 15 patients had a closed rhinoplasty surgery and 15 others had
an open one. By pinpointing 9 spots in the nose, a sensory assessment was made by
means of Semmes-Weinstein monofilaments prior to the surgery and 1 week and 1, 3,
and 6 months after the surgery. RESULTS: In the open and closed groups, there was
hypoesthesia 1 week after the surgery compared with the preoperative period (P =
0.01 and P = 0.016). In the first week a sense reduction in the upper columella
was observed in the open group when compared with the closed one (P = 0.035).
There were no other significant differences between the groups in the nasal
regions at other times. CONCLUSION: It was ascertained that there was reduced
sensation in the upper columella in the open incision group in the first
postoperative week. The sensation was reduced in both groups in the first
postoperative week. The nasal sensation recovered after the first month.
PMID- 27511487
TI - Is the Nexfin finger cuff method for cardiac output measurement reliableduring
coronary artery bypass grafting? A prospective comparison with the
echocardiography and FloTrac/Vigileo methods.
AB - BACKGROUND/AIM: The aim of the current study was to assess the accuracy of
cardiac output (CO) measurements obtained by the Nexfin finger cuff method as
compared with the FloTrac/Vigileo and echocardiography methods in coronary artery
bypass grafting (CABG) patients. MATERIALS AND METHODS: First-time elective CABG
patients were prospectively enrolled in this study and divided into three groups
according to CO measurement method. CO measurements were performed simultaneously
by three different contributors and were collected by the fourth one 24 h
postoperative in the intensive care unit (ICU). Data were statistically analyzed.
RESULTS: Seventeen female and 13 male patients between 42 and 78 years of age
(with a mean of 56 +/- 4) were the subjects of this study. The mean CO
measurements were 5.9 +/- 1.4 L/min, 5.8 +/- 1.1 L/min, and 6.0 +/- 1.1 L/min for
the Nexfin, FloTrac/Vigileo, and echocardiography methods, respectively (P >
0.05). The correlation values between Nexfin and FloTrac/Vigileo, Nexfin and
echocardiography, and FloTrac/Vigileo and echocardiography were r = 0.445, r =
0.377, and r = 0.384, respectively (P < 0.05). CONCLUSION: Nexfin yielded results
comparable to those obtained with FloTrac/Vigileo and echocardiography for the
postoperative CO assessment of CABG patients. Nexfin may be used in
uncomplicated, hemodynamically stable patients in ICU as a reliable and totally
noninvasive method of CO measurement.
PMID- 27511488
TI - Effect of exposure to violence on the development of burnoutsyndrome in ambulance
staff.
AB - BACKGROUND/AIM: The aim of this study is to determine the condition of ambulance
staff (AS) who have been exposed to any kind of violence and to predict risk of
development of burnout syndrome. MATERIALS AND METHODS: Our study was performed
with 120 AS working for the Kirikkale Ambulance Services. During the research,
questionnaires collecting descriptive information and the extent of violence to
which the AS were exposed were administered; participants were asked to fill out
the questionnaire themselves. RESULTS: It was found that 81 (67.5%) participants
had been subjected to at least one type of violence (verbal or physical). Sixty
two percent were exposed to verbal abuse and 55.8% to verbal threats. Rates of
physical threats and attacks were higher among male staff (P = 0.036, P = 0.022),
while the rate of personal accomplishment was determined to be significantly
lower in males (P = 0.006). Emotional exhaustion and depersonalization scores
were determined to be significantly higher in those who perceived less support
from administrators (P = 0.014, P = 0.032). CONCLUSION: All kinds of negative
situations exhaust an individual physically and mentally and lead to the
development of burnout syndrome. AS are more prone to these kinds of situations.
PMID- 27511489
TI - Prevalence and related factors of psoriasis and seborrheic dermatitis: a
community-based study.
AB - BACKGROUND/AIM: We aimed to determine the prevalence of psoriasis (PS) and
seborrheic dermatitis (SD) (erythematous-squamous diseases) in our region and
reveal the frequently encountered associated factors to aid in planning
appropriate healthcare. MATERIALS AND METHODS: A community-based study was
conducted with 85 sample groups that reflected the population rate and demography
of Tokat Province in northern Anatolia. RESULTS: In this community, the
prevalence of PS in people older than 20 years of age was 1.2% and the prevalence
of SD was 5.2%. SD rates were higher in patients who used tobacco and especially
alcohol. SD prevalence was also higher in patients treated for depression and
epilepsy. Furthermore, as education levels increased, SD prevalence increased
proportionally. CONCLUSION: In general, PS prevalence in this region was higher
than in Asia and Africa but lower than in Europe and the United States. Whereas
SD prevalence varies between 2% and 12% throughout the world, the average SD
prevalence was 5.2% in this study.
PMID- 27511490
TI - The role of human papilloma virus and herpes viruses in the etiology of nasal
polyposis.
AB - BACKGROUND/AIM: The aim of this study was to investigate the etiological role of
human papilloma virus (HPV), herpes simplex virus (HSV), varicella-zoster virus
(VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus-6
(HHV-6) and -7 (HHV-7) in the occurrence of nasal polyposis. MATERIALS AND
METHODS: Nasal polyp samples from 30 patients with nasal polyposis and normal
nasal mucosa from 10 patients without nasal polyps were obtained. DNA was
extracted from tissues. Real-time polymerase chain reaction was performed for all
runs. RESULTS: No HSV-1, HSV-2, or VZV was detected in the samples. Among the
patient samples, EBV and HHV-7 DNA were detected in 18 (60%), HHV-6 was detected
in 20 (66.7%), and HPV was detected in 4 (13.3%) samples. Among the controls, CMV
DNA was positive in one (10%). EBV was positive in 5 (50%), HHV-6 and HHV-7 were
positive in 7 (70%), and HPV was positive in 2 (20%) samples. No significant
difference was found among the groups with any test in terms of positivity.
CONCLUSION: The association of Herpesviridae and HPV with the pathogenesis of
nasal polyps was investigated in this study and no relationship was found. Thus,
these viruses do not play a significant role in the formation of nasal polyps.
PMID- 27511491
TI - Retinopathy of prematurity: incidence, risk factors, and evaluation of screening
criteria.
AB - BACKGROUND/AIM: The goal of this study was to investigate the incidence of
retinopathy of prematurity (ROP) and the relationship between risk factors and
disease in premature newborns in our neonatal intensive care unit. MATERIALS AND
METHODS: A total of 219 premature subjects were retrospectively evaluated for
retinopathy. Demographic information, clinical data, and risk factors were
reviewed. RESULTS: The gestational ages of the infants included in the study
ranged between 25 and 36 weeks, and the birth weights ranged between 670 and 4460
g. In this study, the incidence of ROP was 20.1% (44) in preterm infants: 16 had
stage 1 (36.4%), 15 had stage 2 (34.1%), 11 had stage 3 (25%), 1 had stage 4
(2.3%), 1 had stage 5 (2.3%), and 6 had plus (+) disease (7.2%). The risk factors
associated with the development of ROP included low birth weight, ventilation
treatment, bronchopulmonary dysplasia, and maternal preeclampsia. The risk
factors were analyzed with logistic regression analysis. The odds ratios were
5.952 (95% confidence interval [CI]: 2.030-17.447), 20.070 (95% CI: 4.213
95.600), 5.879 (1.916-18.037), and 3.200 (95% CI: 1.002-11.535), respectively.
CONCLUSION: In this study, birth weight, ventilation treatment, bronchopulmonary
dysplasia, and maternal preeclampsia were the most important risk factors for the
development of ROP.
PMID- 27511492
TI - Intraoperative application of 5-fluorouracil and mitomycin C aschemoadjuvants in
primary pterygium surgery.
AB - BACKGROUND/AIM: To compare the effectiveness of intraoperative 5 fluorouracil (5
FU) and mitomycin C (MMC) application in preventing recurrence following primary
pterygium excision. MATERIALS AND METHODS: This was a prospective clinical trial
that included 93 patients with primary pterygia assigned to three treatment
groups in which 29 patients received an intraoperative application of 25 mg/mL 5
FU for 5 min, 32 patients received an intraoperative application of 0.02% MMC for
5 min, and 32 patients underwent only surgical excision (the control group).
Follow-up visits were done on postoperative days 1, 3, 7, 15, and 30, and then
every month. RESULTS: After a mean follow-up of 14 months, the surgical excision
recurrence rates in the 5-FU, MMC, and control groups were 27.6%, 12.5%, and
43.75%, respectively. There was a statistically significant difference in the 5
FU and MMC groups when compared with the control group (chi-square; P = 0.04);
however, the difference between the 5-FU and MMC groups was not significant. No
serious complications were seen in the 5-FU and MMC groups. CONCLUSION:
Intraoperative application of MMC and 5-FU is effective and safe for the
prevention of recurrence. Our findings suggest that MMC is more potent for the
prevention of recurrence and it causes less complaints than 5-FU.
PMID- 27511493
TI - Does the course of laboratory parameters help us to predict the outcome of CCHF?
AB - BACKGROUND/AIM: This study was performed to identify the characteristics
distinguishing fatal and nonfatal cases of patients diagnosed with Crimean-Congo
hemorrhagic fever (CCHF). MATERIALS AND METHODS: A total of 92 patients with
confirmed diagnosis of CCHF in 2009-2013 were included in the study. RESULTS: A
high level of urea and aPTT on the third day of hospital stay, diarrhea,
somnolence, and the interval from the beginning of the symptoms to hospital
admission were independently associated with fatality. Each 10-unit increase in
aPTT and urea levels increased the fatality rate by 3.379-fold and 1.236-fold,
respectively. Delay in hospital admission increased the fatality rate 1.453-fold
for each day of delay. When comparing first and third admission-day laboratory
values, the increase in leukocyte counts and the decrease in CPK, urea,
creatinine, aPTT, PT, INR, and hemoglobin levels were significant in nonfatal
cases. CONCLUSION: This study showed that the course of these laboratory tests
helps us to predict the outcome of the disease. In a few days of hospitalization,
persistence or progress of the abnormal laboratory parameters may warn us about
poor prognosis.
PMID- 27511494
TI - Comparison of galactomannan, beta-D-glucan, and Aspergillus DNA in sera of high
risk adult patients with hematological malignancies for the diagnosis of invasive
aspergillosis.
AB - BACKGROUND/AIM: Invasive aspergillosis (IA) is a fatal infection that is
difficult to diagnose in immunocompromised patients. In this study, Aspergillus
specific DNA was searched using real-time PCR (RT-PCR) in serum samples.
Galactomannan (GM) and/or beta-D-glucan (BDG) tests were previously performed on
these samples for 70 neutropenic patients with hematological malignancy.
MATERIALS AND METHODS: The patients were categorized according to the criteria of
the European Organization for Research and Treatment of Cancer/Mycoses Study
Group (EORTC/MSG). Among the patient serum samples, the first positive GM or BDG
test sample and the median sample of GM or BDG test for negative patients were
used to detect DNA levels by RT-PCR method (Light Cycler 480, Roche Molecular
Biochemicals, Meylan, France) using a commercial kit (Way2Gene Fungi; Genmar,
Izmir, Turkey). RESULTS: When the proven and probable IA group were considered as
real patients, sensitivity of Aspergillus-specific DNA test was 90%, specificity
was 73.3%, positive predictive value was 81.8%, and negative predictive value was
84.6%. CONCLUSION: This study found that searching for specific DNA by RT-PCR
method has a sensitivity as high as the GM test. Although specificity was rather
low, it was concluded that it can be used jointly with GM and BDG tests after
decreasing contamination by severe laboratory applications.
PMID- 27511495
TI - Fully automated morphological analysis of patients with obstructive sleep apnea.
AB - BACKGROUND/AIM: Obstructive sleep apnea syndrome (OSAS) is a disease
characterized by episodic hypoxia. We aimed to use the Freesurfer program for
global evaluation of morphological changes in OSAS patients. MATERIALS AND
METHODS: Three-dimensional T1-weighted images were obtained, and intracranial
morphology was assessed in 18 patients with OSAS and 20 controls. Results of the
volume and the cortical thickness analyses of both groups were compared
statistically. RESULTS: The total cortical, left-right hemispheres gray matter
(GM), corpus callosum, and total GM volumes were lower in OSAS patients when
compared with the control group (P < 0.001). The average cortical thickness was
lower in OSAS patients bilaterally in pars orbitalis, paracentral, rostral middle
frontal, middle frontal, orbital, and superior frontal gyri when compared with
the control group (P < 0.05). Furthermore, the volume and average cortical
thickness of multiple anatomic regions, apart from the brain parts mentioned
above, were decreased unilaterally (e.g., hippocampus, cingulum, putamen,
thalamus) in OSAS patients (P < 0.05). CONCLUSION: Multiple morphologic changes
occur in the cerebral structures of OSAS patients due to intermittent ischemia
episodes. Detection of those areas with Freesurfer is easier. New studies with
large series would be needed for these subjects.
PMID- 27511497
TI - Association analysis of five SNP variants with gout in the Minnan population in
China.
AB - BACKGROUND/AIM: There is a very high prevalence of gout in the Minnan population
in China. We aimed to explore the genetic characteristics and genetic mechanisms
of gout in the Minnan population by studying the association of 5 single
nucleotide polymorphisms (SNPs) with gout. MATERIALS AND METHODS: A total of 163
gout patients and 187 normal controls from Minnan were enrolled in this case
control study. SNPs (rs1165205, rs3733591, rs6855911, rs2231142, rs333049) were
genotyped by allele-specific polymerase chain reaction (PCR) and analyzed with
SPSS 16.0. RESULTS: Significant association with gout was found for rs2231142 (P
< 0.001), consistent with our prior studies. An association between rs1333049 and
gout was also found (P = 0.03) in the Minnan population. No association of SNPs
rs6855911, rs3733591, and rs1165205 was found with gout in the Minnan population.
CONCLUSION: Rs1333049 is associated with gout in the Minnan population, although
rs2231142 shows an even stronger association with gout. The C allele of rs1333049
and the A allele of rs2231142 might be crucial risk factors for gout.
PMID- 27511496
TI - The role of FDG PET/CT in detection of distant metastasis in theinitial staging
of breast cancer.
AB - BACKGROUND/AIM: We aimed to evaluate the role of FDG PET/CT in the detection of
extraaxillary regional nodal/distant metastasis in breast cancer patients and to
assess the value of FDG PET/CT for detecting distant metastases in patient
subgroups. MATERIALS AND METHODS: A total of 254 patients with breast cancer (248
female, 6 male) who underwent PET/CT for initial staging were enrolled. Patients
were divided into four groups: Group 1 consisted of 154 patients diagnosed by tru
cut/core/FNAB, Group 2 comprised 32 patients diagnosed by excisional biopsy,
Group 3 included 62 patients who had mastectomy-axillary lymph node dissection,
and Group 4 consisted of 6 patients who had axillary lymph node metastasis
diagnosed by excisional biopsy. RESULTS: PET/CT detected distant metastasis in 76
of the 254 patients. Of these patients, 21.7% had bone/bone marrow metastasis,
7.1% had lung metastasis, 13% had mediastinal lymph node metastasis, 4.8% had
liver metastasis, 9.8% had other organ/system metastasis, and 6% had other
lymphadenopathies. According to T staging, the percentages of distant metastasis
were as follows: 13.6% of the 66 T1 stage patients, 35.7% of the 129 T2 stage
patients, 40% of the 20 T3 stage patients, and 33.3% of the 39 T4 stage patients.
CONCLUSION: FDG-PET/CT led to a change in the stage of disease and the treatment
approach in newly diagnosed breast cancer patients due to its superiority in
detecting extraaxillary regional lymph node metastases and distant metastases.
PMID- 27511498
TI - Serological prevalence of human parvovirus B19 in diseases or disordersrelated to
different human body systems.
AB - BACKGROUND/AIM: Human parvovirus B19 is a pathogen that affects different parts
of the body. We planned this study because of the lack of data on B19
seroprevalence based on different body-system diseases. MATERIALS AND METHODS:
The prevalence of parvovirus B19 antibodies was investigated retrospectively in
1239 patients by review of medical records from 2009-2012, according to their
diseases classified under general titles in compliance with the International
Classification of Diseases (ICD-10). Parvovirus B19-specific antibodies were
detected by quantitative enzyme immunoassays. RESULTS: The positivity rate was
27.8% for only IgG, 8.5% for only IgM, and 2.6% for both IgG and IgM. The highest
positivity for IgG alone was found in musculoskeletal system and connective
tissue diseases (55.9%), while the highest positivity for IgM was found in
neoplasms (16.4%). The highest positivity for IgG was seen in rheumatoid
arthritis (72.2%) and pregnancy (52.6%), and the highest positivity for total IgM
was found in upper respiratory tract disease (21.0%) and hepatic failure (17.1%).
CONCLUSION: Parvovirus B19 seroprevalence was relatively low in northeastern
Anatolia compared to most serological studies conducted in other regions. We
think that this study has provided the first wide-ranging information on the
seroprevalence of B19 in diseases and disorders of the major human body systems.
PMID- 27511499
TI - Distribution of LDL subgroups in patients with hyperlipidemia.
AB - BACKGROUND/AIM: Low-density lipoproteins (LDLs) have been shown to be a major
risk factor for coronary artery disease. Multiple distinct subspecies have been
identified among LDL particles on the basis of differences in size, density, and
chemical composition. Particles with a diameter of <25.5 nm are defined as small
dense LDL (sdLDL) and have been shown to be associated with increased risk of
coronary disease. Subjects with predominance of sdLDL (pattern B) tend to have
higher levels of triglyceride (TG) and lower levels of high-density lipoprotein
cholesterol (HDL-C). In this study, we investigated the distribution of LDL
subgroups in subjects with different types of hyperlipidemia, such as
hypertriglyceridemia (hyperTG), hypercholesterolemia (hyperCHO), and combined
hyperlipidemia (HL). MATERIALS AND METHODS: We used gradient gel electrophoresis
and a precipitation method with heparin-magnesium reagent to determine LDL
subgroups. RESULTS: It was found that there was a significant (P < 0.02)
association between the lipid panel and LDL subgroups. The percentage of sdLDL in
all HL groups was higher than in controls, and the ratio of sdLDL was highest in
patients with hyperTG. CONCLUSION: The predominance of sdLDL is closely related
to hyperTG and low HDL-C levels.
PMID- 27511500
TI - Determination of regional screening criteria for retinopathy ofprematurity in the
Eastern Black Sea region of Turkey.
AB - BACKGROUND/AIM: To establish a regional screening protocol for retinopathy of
prematurity (ROP). MATERIALS AND METHODS: Data were analyzed from the hospital
records of 1241 infants with gestational age (GA) at birth <=36 weeks and birth
weight (BW) of <=3600 g. RESULTS: The mean GA of the infants was 32.05 +/- 2.7
weeks and the mean BW was 1780.5 +/- 576 g. ROP at any stage was detected in 703
of the 1241 infants (555 female). Eleven infants with type 1 ROP were treated
with 810 nm diode laser photocoagulation. No treatment was needed in infants born
after 33 weeks of gestation and weighing over 1760 g. Logistic regression
analysis showed a significant relationship between the development of ROP and GA,
BW, number of deliveries, respiratory distress syndrome, and treatment with
oxygen or mechanical ventilation. Receiver operating characteristic curve
analysis showed that a GA of 33 weeks or a BW of 1770 g appears to be an
appropriate criterion for identifying infants who may require ROP treatment.
CONCLUSION: GA <= 33 weeks and BW <= 1770 g can be used as screening criteria in
terms of ROP in infants for the Eastern Black Sea region.
PMID- 27511501
TI - The effect of enteral immunonutrition in upper gastrointestinalsurgery for
cancer: a prospective study.
AB - BACKGROUND/AIM: Enteral feeding and immunonutrition (ImN) have been shown to be
associated with a number of favorable effects in patients undergoing cancer
surgery. In this prospective study, we aimed to assess the perioperative use of
enteral immunonutrition in patients undergoing radical gastrointestinal surgery
for malignancy. MATERIALS AND METHODS: Forty-one patients with malignancy were
included in this study and were randomized into one of the two following
nutritional strategies: enteral only (EN) or enteral with enteral immunonutrition
(ENIN). These regimens were followed for 7 days perioperatively by all patients.
Nutritional parameters and postoperative morbidity, mortality, and length of
hospital stay (LHS) were assessed. RESULTS: Serum prealbumin levels increased
significantly in the ENIN group (P = 0.033). Moreover, patients in the ENIN group
showed a more marked decrease in the rate of postoperative infections (P = 0.021)
and anastomotic leakage (P = 0.018) than patients fed with EN. In the EN group,
LHS was significantly longer than that in the ENIN group (18 vs. 12 days) (P =
0.032). Rates of overall morbidity and mortality were similar in the two groups
(P > 0.05). CONCLUSION: ENIN was found to have a favorable effect on the outcome
of radical gastrointestinal surgery for malignancy. Meticulous preoperative
assessment of malnutrition and at least a 7-day perioperative enteral use can
increase the effectiveness of immunonutrition.
PMID- 27511502
TI - Management of hyperbilirubinemia in preterm infants in Turkey.
AB - BACKGROUND/AIM: Prematurity is a significant risk factor for developing
unconjugated hyperbilirubinemia. This study investigated the current approach to
managing hyperbilirubinemia in preterm newborns in Turkey. MATERIALS AND METHODS:
A study-specific questionnaire on the management of jaundice in preterm infants
was sent to 100 level III neonatal intensive care units in Turkey. RESULTS:
Responses were obtained from 84 centers from all regions of Turkey. Of the
centers, 75.3% used the Turkish Neonatology Society guidelines for deciding to
start phototherapy, and 24.7% used different guidelines. The monitoring of
bilirubin varied among the participants. Of the participants, 53.6% believed that
prophylactic phototherapy was necessary if the infant's birth weight was below
1000 g. The participants reported 6 cases of kernicterus in preterm infants in
recent years. CONCLUSION: There is no single standard approach for managing
neonatal hyperbilirubinemia in preterm infants in Turkey. Prophylactic
phototherapy for extremely low birth-weight infants might be added to the
guidelines for Turkey.
PMID- 27511503
TI - Evaluation and identification of IDUA gene mutations in Turkishpatients with
mucopolysaccharidosis type I.
AB - BACKGROUND/AIM: This study aimed to identify IDUA gene mutations in Turkish
patients morphologically (phenotypic) diagnosed with MPS type I. It also sought
to discuss the possible effects of detected mutations on alpha-L-iduronidase
enzyme function based on current knowledge. MATERIALS AND METHODS: Genetic
analysis was carried out in 15 patients using direct DNA sequencing. Moreover,
segregation analysis was performed among family members to predict the pathogenic
effect of novel mutations, and computational programs were used to predict their
functional impact. RESULTS: Nine different mutations (c.494-1G>A, c.793-6C>G,
c.793-5C>A, p.M1L, p.Y64X, p.A327P, p.W402X, p.P533L, and p.R628X) were
identified. Computational analysis results supported the pathogenicity of novel
mutations, suggesting improper splicing. Seven already-known polymorphisms were
detected in the screened cohort as well. CONCLUSION: Our results revealed
heterogeneity in the mutation spectrum of Turkish patients. Six of the mutations,
including the novel ones, have never before been reported in the Turkish
population. Moreover, 5 patients who were phenotypically diagnosed with MPS type
I could not be confirmed by genetic analysis, indicating the importance of the
molecular characterization of MPS subtypes.
PMID- 27511504
TI - The role of baseline Ga-68 DOTATATE positron emission tomography/computed
tomography in the prediction of response to fixed-dose peptide receptor
radionuclide therapy with Lu-177 DOTATATE.
AB - BACKGROUND/AIM: To describe the role of baseline gallium (Ga)-68 DOTATATE
positron emission tomography (PET)/computed tomography (CT) in the prediction of
the response to peptide receptor radionuclide therapy (PRRT) using lutetium (Lu)
177 DOTATATE. MATERIALS AND METHODS: Analysis was made of baseline Ga-68 DOTATATE
PET/CT images of 29 patients (17 females and 12 males; mean age: 50.7 +/- 14.6
years) with metastatic neuroendocrine tumors who received PRRT with Lu-177
DOTATATE. Maximum standardized uptake values (SUVmax) of reference lesions and
their ratios to physiological uptake organs were calculated. The relationship
between these values and the radiological response was analyzed. RESULTS: Partial
response was observed in 8 (28%) patients, stable disease in 18 (62%) patients,
and progressive disease in 3 (10%) patients. Mean SUVmax of reference lesions was
calculated as 23.8 +/- 20.5 (min-max: 5.1-87.3). There was no significant
correlation between radiological responses and SUVmax of reference lesions and
their ratios to other organs. CONCLUSION: Baseline Ga-68 DOTATATE PET/CT helps to
show somatostatin receptor expression status and disease stage in patients who
are candidates for PRRT. However, SUVs do not have a role in the prediction of
treatment response.
PMID- 27511505
TI - Genetic association of the COL1A1 gene promoter -1997 G/T (rs1107946) andSp1
+1245 G/T (rs1800012) polymorphisms and keloid scars in a Jeddah population.
AB - BACKGROUND/AIM: Scars develop at the end of the natural wound-healing process and
are characterized by excessive collagen deposition, particularly types I and III
collagen. This study aimed to investigate the genetic association of COL1A1 -1997
G/T (rs1107946) and COL1A1 Sp1 +1245 G/T (rs1800012) polymorphisms with the
incidence of scars. MATERIALS AND METHODS: A case-control association study was
conducted with 84 volunteers from Jeddah, Saudi Arabia (47 patients and 37
controls). The allele frequency distribution and nucleotide genotypes of -1997
G/T, +1245 G/T were ascertained by polymerase chain reaction (PCR) and
restriction fragment length polymorphism (RFLP) analysis. RESULTS: Our results
indicated that the distribution of COL1A1 (rs1107946) genotypes was significantly
different between patients and controls (P = 0.00). The incidence of COL1A1
(rs1107946) genotype GG was significantly associated with a risk of scars. The
distribution of the (rs1107946) genotype was drastically higher in women with
scars (P= 0.00). One haplotype block in COL1A1 was documented by the pair-wise
linkage disequilibrium between the single nucleotide polymorphisms (SNPs). The
frequency of the GG haplotype constructed by the two SNPs was robustly high and
associated with risk of scars. CONCLUSION: Our results strengthen the evidence
for the association between polymorphisms of -1997 G/T, +1245 G/T of the COL1A1
gene in the genetic etiology of keloid scars.
PMID- 27511506
TI - Posterior laminoforaminotomy in the treatment of lateralcervical herniated disc
and foraminal stenosis.
AB - BACKGROUND/AIM: Posterior cervical laminoforaminotomy is an effective surgical
treatment in selected cases of cervical radiculopathy caused by posterolateral
herniated discs or foraminal stenosis. The aim of the present study was to
evaluate the surgical techniques, rates of complications, long-term outcomes,
advantages, and disadvantages of keyhole foraminotomy retrospectively. MATERIALS
AND METHODS: Keyhole foraminotomy was performed in 83 patients. In 51 patients
(61.5%) soft disc herniation was removed, and in 32 of them (38.5%) osteophytes
were evident. The clinical data were evaluated according to Odom's criteria, and
the mean follow-up time was 6 months. RESULTS: Postoperative results were classed
as excellent in 66 patients (79.5%), good in 13 patients (15.7%), fair in 3
patients (3.6%), and poor in only 1 patient (1.2%). Radiculopathy symptoms
regressed in 79 patients (95%). Among the 83 patients, surgical complications
(dural injury and level error) were noted in 2 patients (2.4%). CONCLUSION:
Posterior laminoforaminotomy is applied to selected patients with a low
complication rate. The advantages of this surgery are suitable visualization of
the nerve root, preserved motion of the operated segment, avoidance of cervical
instability, and a decrease in the length of hospital stay.
PMID- 27511507
TI - Common variable immunodeficiency in adults requires reserved protocols for long
term follow-up.
AB - BACKGROUND/AIM: The aim of this study is to establish follow-up protocols for
adult patients with common variable immunodeficiency (CVID) in a recently founded
adult immunology clinic in the Central Anatolia Region of Turkey, where a
clinical immunology center for adults was not available previously. MATERIALS AND
METHODS: A total of 25 patients with CVID aged 18 years and older were included
in this study. The file format consisted of 13 pages and was developed for the
purpose of the study. Separate sections were designated for identity information,
medical history, disease course, previous and current laboratory and imaging
studies, follow-up plans, detection and management of
complications/comorbidities, and treatment results. RESULTS: The mean age of the
patients was 36.6 +/- 13.4 years. The delay in diagnosis was 107 +/- 95.6 months.
In 92% of patients, initial symptoms resulting in admission to healthcare
facilities were infections. Seventeen of 25 patients (68%) had bronchiectasis at
the beginning of follow-up. CONCLUSION: Early identification of complications and
comorbidities in patients with CVID will significantly improve quality of life
and survival. Close observation and standardized protocols for follow-up are
essential components of management.
PMID- 27511508
TI - Is silicone stent insertion a clinically useful option for tracheobronchomalacia?
AB - BACKGROUND/AIM: Tracheobronchomalacia (TBM) leads to the obstruction of
expiratory airflow and interference with secretion clearance. Stabilization of
the airway wall using a silicon stent or laser coagulation of the posterior wall
may be treatment options. This study aimed to retrospectively analyze which
interventional bronchoscopic method could be used to provide airway stabilization
and gain control of symptoms and for whom this method could be used. MATERIALS
AND METHODS: Fifteen patients who had received treatment in our interventional
pulmonology unit were analyzed. We analyzed the techniques used, stent duration,
complications, and long-term treatment success retrospectively. RESULTS: Stents
were used in 10 patients: 4 patients had silicon Y-stents and 4 patients had
silicon tracheal stents. Stents were removed due to early migration in 3
patients. In 5 of the 7 cases, the stent was removed due to frequent obstructions
of the stent due to recurrent severe mucostasis. A suitable stent was not found
for one patient who had an extremely enlarged trachea. Good clinical results were
achieved in just two cases. The frequency of admissions to the emergency room and
hospitalizations were diminished during the follow-up time in these two patients.
CONCLUSION: Silicon stents may be a good treatment option in selected patients
with TBM and dynamic collapse. However, our patients were high-risk; thus, the
criteria for candidates for bronchoscopic treatment should be carefully defined.
PMID- 27511509
TI - Physical activity and physical fitness in obese, overweight, and normal-weight
children.
AB - BACKGROUND/AIM: The aim was to assess the differences between physical activity
and physical fitness in obese, overweight, and normal-weight children. MATERIALS
AND METHODS: The cross-sectional study was accomplished using cluster sampling
method at 3 Lithuanian schools. An analysis of anthropometric data for 532
Lithuanian children was performed. Height, weight, waist and hip circumferences,
and skinfold thickness were measured. Body mass index, waist-to-hip ratio, and
body fat percentage were calculated. The Youth Physical Activity Questionnaire
and a 6-min walk test (6MWT) were administered to evaluate physical activity and
physical fitness. Maximal oxygen consumption was calculated to assess the
children's aerobic capacity. Correlations among anthropometric data, 6MWT-walked
distance, and moderate-vigorous physical activity duration were analyzed.
RESULTS: The study showed that 20.1% of the studied children were obese or
overweight. They engaged in moderate-to-vigorous physical activity 22.4 min less
per day and walked 50.9 m less on average during a 6-min test than normal-weight
children. Physical fitness parameters correlated with daily moderate-vigorous
physical activity duration and with most of the children's anthropometric
parameters. CONCLUSION: Obese and overweight children were less physically active
and had lower physical fitness than normal-weight children. The findings
underline the need for interventions to increase physical activity and improve
fitness in obese and overweight children.
PMID- 27511510
TI - The prevalence of tularemia in occupational groups that have contact with
animals.
AB - BACKGROUND/AIM: The aim of the current study was to investigate the presence of
antibodies against Francisella tularensis in individuals in different occupations
that have contact with animals in the Kars region of northeastern Turkey.
MATERIALS AND METHODS: A total of 201 blood samples specifically including 103
farmers, 45 clinical veterinarians, 42 butchers, and 11 hunters were analyzed.
The results of the study were reported in relation to some sociodemographic
features (age, sex, occupation, and experience) of the volunteers. The presence
of antibodies was determined by a microagglutination (MA) test. In addition,
positive sera were confirmed using an ELISA kit. RESULTS: Fifteen (7.46%)
individuals, including fourteen farmers and one clinical veterinarian, were found
to be positive for F. tularensis by both MA and ELISA with a titer range of 1/10
to 1/160. The highest seroprevalence rate was observed in farmers (13.59%),
followed by clinical veterinarians (2.22%). The occurrence of tularemia was found
to increase with age. CONCLUSION: Though the main route of tularemia outbreaks is
water-borne in Turkey, it was determined that people whose occupations bring them
into contact with animals are at risk. Similar studies are recommended in order
to further clarify the epidemiology of the disease in the northeast of Turkey.
PMID- 27511511
TI - Amniotic membrane transplantation in bacterial and herpetic stromal keratitis.
AB - BACKGROUND/AIM: The aim of this study was to describe the results of amniotic
membrane transplantation (AMT) in patients with bacterial and herpetic stromal
keratitis. MATERIALS AND METHODS: This was a retrospective chart review study
including 42 patients with herpetic keratitis (group 1) and 42 patients with
bacterial keratitis (group 2). AMT was performed in addition to antimicrobial
therapy. Topical steroids were administered after surgery. The outcome parameters
evaluated were epithelialization time, decrease of stromal inflammation, and
uncorrected visual acuity (UCVA). RESULTS: The average age of our patients was
55.85 +/- 19.07 years, and average follow-up was 14.70 +/- 11.75 months. The
period of epithelialization was 19.23 +/- 7.32 days in the herpetic group and
19.31 +/- 6.30 days in the bacterial group. Descemetocele developed in 2 patients
of the herpetic group. Other patients in both groups completed epithelialization
after AMT procedures with varying amounts of corneal scarring. The bacterial
group showed an improvement in UCVA, but the herpetic group showed no improvement
in UCVA. CONCLUSION: AMT is a convenient approach for the treatment of corneal
keratitis resistant to conventional treatment and allows the use of early topical
steroid application. It provides patients with corneal scarring an opportunity
for subsequent keratoplasty by arresting the inflammatory response.
PMID- 27511513
TI - Growth of biometric components and development of refractive errors in premature
infants with or without retinopathy of prematurity.
AB - BACKGROUND/AIM: To investigate the biometric components and refractive errors in
premature infants with or without retinopathy of prematurity (ROP). MATERIALS AND
METHODS: Anterior chamber depth, lens thickness, vitreous length, and axial
length were measured with an ultrasound biometer. Cycloplegic refraction was
performed by streak skiascopy. Infants with or without ROP were grouped according
to postmenstrual age at the time of ocular examination: Group 1, <=33 weeks;
Group 2, 34-37 weeks; Group 3, 38-41 weeks; Group 4, 42-45 weeks; Group 5, >=46
weeks. RESULTS: The mean postnatal age of 894 infants (451 females and 443 males)
was 8.7 +/- 4.5 weeks, gestational age was 30.9 +/- 2.8 weeks, and birth weight
was 1506 +/- 484 g. In Group 2, the mean vitreous length and axial length of
infants with ROP were significantly lower than those of infants without ROP (P =
0.011, P = 0.001). The mean anterior chamber depth, lens thickness, spherical
equivalent, and astigmatism in all groups did not differ significantly among the
infants with or without ROP (P > 0.05). CONCLUSION: The anterior chamber depth,
lens thickness, vitreous length, and axial length showed a linear growth
throughout the follow-up period. The maximum elongation was observed in vitreous
length and axial length.
PMID- 27511512
TI - Review of 306 evisceration surgeries performed between 2005 and 2013.
AB - BACKGROUND/AIM: The purpose of the present study was to evaluate the reasons for
eye evisceration surgeries performed from 2005 to 2013 in our clinic. MATERIALS
AND METHODS: The medical records of patients who underwent evisceration surgery
over the past 9 years were retrospectively evaluated. Detailed data were
reviewed, with a focus on the first precipitating factor for evisceration.
RESULTS: Of the 306 patients who underwent evisceration surgery in the studied
period, 111 (36.27%) were female (with a mean age of 41.56 +/- 21.38 years) and
195 (63.73%) were male (with a mean age of 37.76 +/- 21.92 years). The most
common cause of evisceration was ocular trauma (184 patients; 60.1%). Male
patients experienced significantly more trauma, while glaucoma was more common in
female patients. CONCLUSIONS: Eye removal is devastating for both patients and
their relatives, and its most important and preventable cause is ocular trauma.
PMID- 27511514
TI - The role of 18F-FDG PET-CT in the detection of unknown primary malignancy: a
retrospective study.
AB - BACKGROUND/AIM: This study aimed to retrospectively evaluate the role of 18F-FDG
PET/CT imaging in the detection of unknown primary tumor sites in patients with a
suspicious malignancy. MATERIALS AND METHODS: We retrospectively examined the 18F
FDG PET/CT images of 50 unknown primary malignancy patients. The malignancy of
the lesions with increased 18F-FDG uptake on PET images was defined by
interpreting the nondiagnostic CT images that were obtained with the PET study.
The primary tumor site was decided according to the combined PET/CT findings, and
the results were subsequently confirmed with a histopathological examination.
RESULTS: Fifty patients (29 M; 21 F) aged 18-85 years were included in the study.
The sample included 32 malignant and 18 benign lesions according to the
histopathological evaluation. 18F-FDG PET/CT study accurately identified
malignant lesions in 28 (average SUVmax +/- SD: 8.27 +/- 7.22) and benign lesions
in 12 (average SUVmax +/- SD: 3.63 +/- 3.07) patients; these findings were
histopathologically confirmed. PET/CT correctly detected the primary tumor site
in 16 (50%) of 32 patients. CONCLUSION: 18F-FDG-PET/CT identified the primary
tumor site well in 50% of our cases. We propose that 18F-FDG PET/CT imaging may
help to accurately detect malignant lesions in patients with unknown primary
tumors.
PMID- 27511515
TI - Glycemic index values of monofloral Turkish honeys and the effect oftheir
consumption on glucose metabolism.
AB - BACKGROUND/AIM: Clinical trials have shown that low glycemic index (GI) nutrition
reduces mean blood glucose concentrations and insulin secretions. The aim of the
present study was to determine the GI values of various monofloral (citrus, milk
vetch, chestnut, thyme, lime, pine) honeys of Turkey, and the effect of their
consumption on glucose metabolism. MATERIALS AND METHODS: Processing data from 20
healthy volunteers, GI values were determined from the glycemia values by using
the incremental area method. Serum insulin and C-peptide levels were also
measured before and 120 min after the test. RESULTS: The GI values of citrus,
thyme, lime, chestnut, pine, and milk-vetch honeys were found to be 44.9, 52.6,
55.3, 55.5, 58.8, and 69, respectively. Serum insulin and C-peptide values after
honey consumption were relatively lower than those after reference food (glucose)
consumption. By the end of the 120 min, serum insulin levels were significantly
higher, while a significant decrease was observed after the consumption of
chestnut honey (P < 0.05). CONCLUSION: Citrus and thyme honeys were determined to
have low GI, while serum insulin levels were significantly lower after the
consumption of chestnut honey. Long-term research is needed to compare the
effects of honey consumption on healthy and diabetic individuals.
PMID- 27511517
TI - Nail changes in patients with inflammatory bowel diseases.
AB - BACKGROUND/AIM: Inflammatory bowel disease (IBD) is a group of inflammatory
conditions of the colon and small intestine. To our knowledge, no studies to date
pertain to the profile of nail changes in IBD, except for onychomycosis. We aimed
to study the frequency and pattern of nail changes among patients with IBD and
evaluate their potential relationships with several parameters in IBD. MATERIALS
AND METHODS: The study included 73 patients with IBD and 51 healthy control
subjects. Nails of both groups were examined for changes with regard to color,
striations, texture, curvature of nail plates, dystrophy of nail plates, and
pigmentation. Mycological examinations were performed when onychomycosis was
suspected. RESULTS: Nail changes were statistically higher in patients with IBD
than in the control group (P = 0.001). The presence of onychomycosis was
significantly more common in patients with IBD (P = 0.041). Subungual
hyperkeratosis and brownish discoloration of the nail were the most common
findings in patients with IBD. CONCLUSION: Our study is the first report showing
all nail changes in IBD. Further studies with more subjects are needed to reveal
more detailed information about nail changes in IBD.
PMID- 27511516
TI - Evaluation of maternal serum folate, vitamin B12, and homocysteine levels
andfactor V Leiden, factor II g.20210G>A, and MTHFR variations in
prenatallydiagnosed neural tube defects.
AB - BACKGROUND/AIM: Neural tube defects (NTDs) are common congenital malformations
that develop as a result of interactions between several genes and environmental
factors. Many factors have been investigated in order to understand the etiology
of NTDs, and many studies have identified folate intake as a common contributing
factor. The exact etiology of the disease is still unknown. MATERIALS AND
METHODS: In this study, we compared serum folate, vitamin B12, and homocysteine
levels, along with common thrombophilia-related genetic variations, including
factor V Leiden, factor II g.20210G>A, MTHFR c.677C>T, and MTHFR c.1298A>C, in 35
pregnant women with fetal NTDs and 38 pregnant women with healthy fetuses.
RESULTS: A significant difference in serum vitamin B12 level and factor V Leiden
frequency was detected between the two groups. On the other hand, serum folate,
homocysteine levels, and factor II g.20210G>A, MTHFR c.677C>T, and MTHFR
c.1298A>C were not significantly different in the NTD group compared to the
controls. CONCLUSION: These results indicate that vitamin B12 supplementation
along with folate may help in lowering NTD frequency. In addition, this is the
first study that provides evidence for a possible relationship between increased
NTD risk and factor V Leiden.
PMID- 27511518
TI - Traditional practices of Konya women during pregnancy, birth, the
postpartumperiod, and newborn care.
AB - BACKGROUND/AIM: The purpose of the present study was to identify traditional
practices and the extent to which they are practiced by mothers during pregnancy,
birth, the postpartum period, and newborn care. MATERIALS AND METHODS: This study
was conducted in the city center of Konya (Turkey). Data were collected through
questionnaires completed by volunteers. The research sample comprised 450
mothers, all of whom had given birth to at least one live baby. The forms were
completed during face-to-face interviews. RESULTS: Some traditional pregnancy
practices were followed by 70.7% of the participants. Of the women who performed
these practices, 57.4% consciously chose foods they craved, tried not to take
nutrients believed to be unsuitable in pregnancy, and took nutrients believed to
influence the sex of the baby; 85.6% reported breastfeeding their babies in the
first 4 h after birth and 9.7% waited for the first call to prayer (azan) to
start breastfeeding. Additionally, 72.2% of the mothers reported performing
kirklama (making the forties), a ceremony performed to celebrate the 40th day
after a baby's birth. CONCLUSION: Most of the women who participated in the study
still followed some traditional practices and rituals during pregnancy and the
postpartum period. Therefore, health care professionals should provide health
education that accounts for the women's cultural and social environment.
PMID- 27511519
TI - Free radical-induced nephrotoxicity following repeated oral exposureto
chlorpyrifos alone and in conjunction with fluoride in rats.
AB - BACKGROUND/AIM: Chronic renal disorder is becoming a major health problem
worldwide. The purpose of the present study was to investigate alterations in the
renal antioxidant system in rats induced by repeated exposure to chlorpyrifos
(CPF) alone and in conjunction with fluoride. MATERIALS AND METHODS: Wistar rats
were randomly allocated to seven groups, each consisting of six rats, and were
subjected to different treatment regiments for 28 days. RESULTS: Significant
increases (P < 0.05) in plasma protein, blood urea nitrogen, and creatinine
levels indicated alterations in renal functions on repeated exposure to CPF or
fluoride; moreover, these changes were more pronounced in animals exposed to both
toxicants concurrently. A significant increase (P < 0.05) in malondialdehyde
levels and decreases in superoxide dismutase, catalase, and glutathione
peroxidase activities in renal tissue were noted, indicating renal damage on
exposure to CPF, fluoride, or the combination of those. CONCLUSION: Our
observations suggested that the concurrent exposure to CPF and fluoride increased
the extent of renal damage. These findings indicate that this damage is due to
increased free radical formation and a reduced function of the antioxidant system
in renal tissue. Thus, the application of CPF as an insecticide should be reduced
in areas where the fluoride levels in ground waters are high in order to minimize
renal damage in exposed populations.
PMID- 27511520
TI - Combination immunotherapy with extract of heated 4T1 and naloxone in mouse model
of breast cancer.
AB - BACKGROUND/AIM: This study was designed to investigate the efficacy of a new
vaccine against breast cancer, which was made by mixing the extract of heated 4T1
cells and naloxone, as an adjuvant. MATERIALS AND METHODS: Female BALB/c mice of
6-8 weeks old were challenged subcutaneously in the right flanks with 4T1 cells.
When all animals developed a palpable tumor, immunotherapy was initiated. Mice in
the experimental groups received, twice with a 1-week interval, either the
extract of heated 4T1 alone or in combination with naloxone, and mice in the
negative control group received phosphate-buffered saline. One week after the
last immunotherapy, half of the mice were euthanized in order to determine the
immune response profile. The remaining animals were kept until the time when
death occurred spontaneously. RESULTS: The combined-treated mice with mammary
tumors showed a more favorable survival curve and slower rate of tumor
development compared to the mice with tumors that received only heated 4T1 and/or
negative control mice. Moreover, the combined immunization significantly
amplified the respiratory burst potential and the secretion of IFN-gamma, and,
conversely, diminished the secretion of IL-4, IL-10, and TGF-beta in the
splenocyte population compared to splenocytes from other groups. CONCLUSION: The
combined naloxone and heated 4T1 cells promote beneficial outcomes in the mouse
model of breast cancer.
PMID- 27511521
TI - Comparison between the protective effects of vitamin K and vitamin A on the
modulation of hypervitaminosis D3 short-term toxicity in adult albino rats.
AB - BACKGROUND/AIM: Vitamin D3 has increased risk of toxicity due to its common use
in multivitamin preparations. Vitamin K and vitamin A play an important role in
vitamin D action. The goal of the current study was to compare the protective
effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3
toxicity in rats by assessing serum calcium, renal function tests, cardiac
enzymes, and related histopathological changes. MATERIALS AND METHODS: Eighty
adult albino rats were divided into four groups; each group consisted of 20 rats.
The first group received water; the second received a toxic dose of vitamin D3;
the third received a toxic dose of vitamin D3 with vitamin A; and the fourth
received a toxic dose of vitamin D3 with vitamin K. RESULTS: Vitamin D3 toxicity
led to significant abnormalities of cardiac enzymes, renal function tests, and
serum calcium associated with histopathological changes in the kidney, heart,
lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin
K with a toxic dose of vitamin D improved the biochemical and histopathological
abnormalities of hypervitaminosis D3. CONCLUSION: Vitamins A and K showed the
same protective effects in the modulation of hypervitaminosis D3 short-term
toxicity.
PMID- 27511522
TI - Evaluation of the effectiveness of biodegradable electrospun caprolactoneand
poly(lactic acid-epsilon-caprolactone) nerve conduits for peripheral
nerveregenerations in a rat sciatic nerve defect model.
AB - BACKGROUND/AIM: The aim of this study was to compare electrospun caprolactone
(EC) and poly(lactic acid-epsilon-caprolactone) (PLCL) nerve conduits with nerve
graft in a rat sciatic nerve defect model. MATERIALS AND METHODS: A total of 32
male Wistar albino rats were divided into 4 groups, with 8 rats in each group. A
nerve defect of 1 cm was constructed in the left sciatic nerve of the rats. These
defects were left denuded in the sham group, and reconstructed with nerve grafts,
PLCL, and EC nerve conduits in the other groups. After 3 months, nerve
regenerations were evaluated macroscopically, microscopically, and
electrophysiologically. The numbers of myelinated axons in the cross-sections of
the nerves were compared between the groups. RESULTS: Macroscopically, all nerve
coaptations were intact and biodegradation was detected in nerve conduits.
Electromyographic assessment and count of myelinated axons in the cross-sections
of the nerves displayed the best regeneration in the nerve graft group (P <
0.001) and similar results were obtained in the PLCL and EC nerve conduit groups
(P = 0.79). Light and electron microscopy studies demonstrated nerve regeneration
in both nerve conduit groups. CONCLUSION: EC nerve conduits and PLCL nerve
conduits yielded similar results and may be alternatives to nerve grafts as they
biodegrade.
PMID- 27511523
TI - Ameliorating effects of curcumin on nicotine-induced mice testes.
AB - BACKGROUND/AIM: The aim of this study was to determine the antioxidative effect
of curcumin on nicotine-induced mice testis. MATERIALS AND METHODS: Sixty Swiss
albino male mice were divided into five groups, each containing 12 mice. The
first group was used as a control. To induce toxicity in the second and third
group, nicotine (0.4 mg/kg/day) was injected intraperitoneally into mice for 14
and 28 days, respectively. The mice in the fourth and fifth group were injected
with nicotine (0.4 mg/kg/day) and orally treated with curcumin (200 mg/kg) for 14
and 28 days, respectively. Testosterone levels were measured from blood samples
and testis tissues were examined under light and electron microscopes. RESULTS:
Light and electron microscopic examinations of the nicotine-induced groups showed
evident degenerations in spermatogenic cells, Sertoli cells, and Leydig cells.
The groups treated with curcumin had less testicular alterations. The mice that
were sacrificed after 28 days in the groups treated with curcumin showed minor
degenerations. Furthermore, the median levels of testosterone significantly
decreased in the nicotine-induced groups in comparison with those in the control
group. CONCLUSION: The results indicated that curcumin might be a potential
therapeutic agent for testicular injury caused by nicotine addiction.
PMID- 27511524
TI - The protective effect of Capparis ovata in acute hepatotoxicity induced by
paracetamol.
AB - BACKGROUND/AIM: To investigate the efficiency of Capparis ovata as a protective
agent against acute paracetamol toxicity of the liver. MATERIALS AND METHODS: A
total of 36 Wistar albino rats were divided into 4 groups: 1) paracetamol, 2)
Capparis ovata + paracetamol, 3) Capparis ovata, and 4) control. Groups 2 and 3
were given Capparis ovata and Groups 1 and 4 distilled water for 8 days. On day
8, 3000 mg kg-1 paracetamol was administered orally to Groups 1 and 2. Samples
were taken on day 9. AST, ALT, total bilirubin, direct bilirubin, GGT, and ALP
levels were assessed. Lipid peroxidation markers and thiobarbituric acid-reactive
substance (TBARS) levels were measured in the blood and liver. Liver tissues were
evaluated histologically. RESULTS: AST, ALT, and total bilirubin levels were
lower in Group 2 than in Group 1 (P < 0.05). TBARS levels were lower in Groups 2
(P = 0.000), 3 (P = 0.001), and 4 (P = 0.001) than in Group 1. Degenerative
findings were lower in the Capparis ovata + paracetamol group than in the
paracetamol group (P < 0.05). CONCLUSION: It can be concluded that Capparis ovata
has a protective effect on the liver, both histopathologically and biochemically,
against paracetamol-induced liver injury.
PMID- 27511525
TI - Efficacy of pegylated liposomal etoposide nanoparticles on breast cancer cell
lines.
AB - BACKGROUND/AIM: This study aimed to investigate the efficacy of pegylated
liposomal etoposide nanoparticles (NPs) against T-47D and MCF-7 breast cancer
cell lines. MATERIALS AND METHODS: Pegylated liposomal etoposide NPs were
prepared by reverse phase evaporation method. The size, size distribution, and
zeta potential of the NPs was measured by a Zetasizer instrument. The
cytotoxicity of NPs was inspected by methyl thiazol tetrazolium assay. The
release pattern of the drug from the vesicles was studied by the dialysis method.
Drug loading and encapsulation efficiency (EE) were also measured. RESULTS: The
mean size, size distribution, and zeta potential of pegylated liposomal etoposide
NPs were 491 +/- 15.5 nm, 0.504 +/- 0.14, and -35.8 +/- 2.5 mV, respectively.
Drug loading and EE were 10.3 +/- 1.6% and 99.1 +/- 2.8%, respectively. The
etoposide release in the formulation was estimated at about 3.48% after 48 h. The
cytotoxicity effect of etoposide NPs on T-47D and MCF-7 cell lines of breast
cancer showed higher antitumor activity as compared with those of the free drug.
CONCLUSION: Liposome-based NPs may hold great potential as a drug delivery
system.
PMID- 27511526
TI - Role of FLT3 in the proliferation and aggressiveness of hepatocellular carcinoma.
AB - BACKGROUND/AIM: Previously we showed that Fms-like tyrosine kinase (FLT3) changes
its cellular localization upon partial hepatectomy, suggesting a role in liver
regeneration. FLT3 was also shown to play an important function in cellular
proliferation and activation of PI3K and Ras. Thus, we aimed to investigate the
role of FLT3 in hepatocellular tumorigenesis utilizing in vitro and in vivo
models. MATERIALS AND METHODS: We used Snu398 cells that express FLT3. We
investigated these cells' in vitro proliferation and invasion abilities by
treatment with the FLT3 inhibitor K-252a or by knocking-down with FLT3 shRNA,.
Furthermore, the effect of blocking FLT3 activity and expression during in vivo
tumorigenesis was assessed with xenograft models. RESULTS: After K-252a treatment
or stable knock-down, these cells' proliferation and migration abilities were
highly diminished in vitro. In addition, significant diminution in tumorigenicity
of Snu398 cells was also obtained in vivo. When FLT3 knocked-down Snu398 cells
were injected into nude mice, we did not detect alphaSMA expression in these
tumors, suggesting a role for FLT3 in in vivo invasiveness. CONCLUSION: Our data
provided evidence that FLT3 has a crucial role both in hepatocarcinogenesis and
its invasiveness. Therefore, targeting FLT3 and/or its activity may be a
promising tool for combating hepatocellular carcinomas.
PMID- 27511527
TI - Aqueous synthesis of highly stable CdTe/ZnS Core/Shell quantum dots for
bioimaging.
AB - In this work, we report the synthesis, characterization and biological
application of highly stable CdTe/ZnS (cadmium tellurite/zinc sulphide)
Core/Shell (CS) quantum dots (QDs) capped with mercaptosuccinic acid (MSA). The
CS QDs were synthesized using a simple one-pot aqueous method. The synthesized
CdTe/ZnS CS QDs were found to exhibit excellent stability even 100 days after
preparation and also showed better photoluminescence quantum yield (PLQY) of
about 50% compared with that of only CdTe QDs which was nearly 12%. The formation
of the CdTe/ZnS CS was confirmed by high-resolution transmission electron
microscopy (HR-TEM), and Fourier transform infra-red (FTIR) and X-ray diffraction
(XRD) analyses. Further, on extending our study towards bioimaging of E. coli
cells using the QDs samples, we found that CdTe/ZnS CS QDs showed better results
compared with CdTe QDs.
PMID- 27511528
TI - Nickel-catalyzed transfer hydrogenation of ketones using ethanol as a solvent and
a hydrogen donor.
AB - We report a nickel(0)-catalyzed direct transfer hydrogenation (TH) of a variety
of alkyl-aryl, diaryl, and aliphatic ketones with ethanol. This protocol implies
a reaction in which a primary alcohol serves as a hydrogen atom source and
solvent in a one-pot reaction without any added base. The catalytic activity of
the nickel complex [(dcype)Ni(COD)] (e) (dcype: 1,2-bis(dicyclohexyl
phosphine)ethane, COD: 1,5-cyclooctadiene), towards transfer hydrogenation (TH)
of carbonyl compounds using ethanol as the hydrogen donor was assessed using a
broad scope of ketones, giving excellent results (up to 99% yield) compared to
other homogeneous phosphine-nickel catalysts. Control experiments and a mercury
poisoning experiment support a homogeneous catalytic system; the yield of the
secondary alcohols formed in the TH reaction was monitored by gas chromatography
(GC) and NMR spectroscopy.
PMID- 27511529
TI - Photodetectors: Broad Detection Range Rhenium Diselenide Photodetector Enhanced
by (3-Aminopropyl)Triethoxysilane and Triphenylphosphine Treatment (Adv. Mater.
31/2016).
AB - The effects of triphenylphosphine (PPh3 ) and (3-amino-propyl)triethoxysilane
(APTES) on a rhenium diselenide (ReSe2 ) photodetector are systematically studied
by J.-H. Park and co-workers on page 6711 in comparison with a conventional MoS2
device. A very high performance ReSe2 photodetector is demonstrated, which has a
broad photodetection range, high photoresponsivity (1.18 * 10(6) A W(-1) ), and
fast photoswitching speed (rising/decaying time: 58/263 ms).
PMID- 27511531
TI - Wearable Strain Sensors: Carbonized Silk Fabric for Ultrastretchable, Highly
Sensitive, and Wearable Strain Sensors (Adv. Mater. 31/2016).
AB - A novel carbonized plain-weave silk-fabric-based wearable strain sensor is
proposed by Y. Y. Zhang and co-workers on page 6640. The sensor can be stretched
up to 500% with high sensitivity in a wide strain range and can be assembled into
wearable devices for the detection of both large and subtle human activities,
showing great potential in human-motion detection and robotics.
PMID- 27511532
TI - Flexible Batteries: Hierarchical Assemblies of Carbon Nanotubes for Ultraflexible
Li-Ion Batteries (Adv. Mater. 31/2016).
AB - An advanced battery architecture composed of 3D carbon nanotube (CNT) current
collectors is used to mitigate stresses in flexible batteries. On Page 6705, C.
George, M. De Volder, and co-workers describe the fabrication process and
characteristics of this new generation of ultraflexible batteries, which show
high rate and cyclablility. These batteries may find applications in the powering
of flexible displays and logics.
PMID- 27511533
TI - Perovskite Solar Cells: High Efficiency Pb-In Binary Metal Perovskite Solar Cells
(Adv. Mater. 31/2016).
AB - On page 6695, X. Y. Gao, L.-S. Liao, and co-workers describe the fabrication of
mixed Pb-In perovskite solar cells, using indium (III) chloride and lead (II)
chloride with methylammonium iodide. A maximum power conversion efficiency as
high as 17.55% is achieved owing to the high quality of the perovskites with
multiple ordered crystal orientations. This work demonstrates the possibility of
substituting the Pb (II) by using In (III), which opens a broad route to
fabricating alloy perovskite solar cells with mitigated ecological impact.
PMID- 27511534
TI - High-Resolution Electronics: Spontaneous Patterning of High-Resolution
Electronics via Parallel Vacuum Ultraviolet (Adv. Mater. 31/2016).
AB - On page 6568, T. Minari and co-workers describe spontaneous patterning based on
the parallel vacuum ultraviolet (PVUV) technique, enabling the homogeneous
integration of complex, high-resolution electronic circuits, even on large-scale,
flexible, transparent substrates. Irradiation of PVUV to the hydrophobic polymer
surface precisely renders the selected surface into highly wettable regions with
sharply defined boundaries, which spontaneously guides a metal nanoparticle ink
into a series of circuit lines and gaps with the widths down to a resolution of 1
MUm.
PMID- 27511589
TI - An investigation on the interaction modes of a single-strand DNA aptamer and RBP4
protein: a molecular dynamic simulations approach.
AB - Type two diabetes is one of the primary health issues threatening public well
being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol
binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer
ssDNA aptamer instead of conventional antibodies. However, there is no structural
information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to
RBP4 still remains unexplored. The objective of the present study is to achieve a
better understanding of specific binding interactions of the target protein
(RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide
detailed information on fluctuations, conformational changes, critical bases and
effective forces to develop regulated aptamers to be employed in designing new
aptamers for many useful recognition applications. RBA was designed according to
its reported base pair sequence and secondary structure. The HADDOCK on line
docking program was used to predict a suitable RBP4-RBA mode of interaction to
start MDs with. MDs methodology was used to analyze the final complex stability
and detect interacting residues. Eventually, we conclude that single strand
located bases are the key components that conduct the intercalation phenomenon
with big targets rather than those involving loops and folded motifs, to
encompass targets and probably inhibit their activity. Also, UV-visible, circular
dichroism and fluorescence spectroscopy measurements confirmed the interactions
between RBA and RBP4 and RBP4-RBA complex formation.
PMID- 27511536
TI - Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase
activity of SAMHD1 can not explain the retroviral restriction defect.
AB - SAMHD1, a dNTP triphosphohydrolase, contributes to interferon signaling and
restriction of retroviral replication. SAMHD1-mediated retroviral restriction is
thought to result from the depletion of cellular dNTP pools, but it remains
controversial whether the dNTPase activity of SAMHD1 is sufficient for
restriction. The restriction ability of SAMHD1 is regulated in cells by
phosphorylation on T592. Phosphomimetic mutations of T592 are not restriction
competent, but appear intact in their ability to deplete cellular dNTPs. Here we
use analytical ultracentrifugation, fluorescence polarization and NMR-based
enzymatic assays to investigate the impact of phosphomimetic mutations on SAMHD1
tetramerization and dNTPase activity in vitro. We find that phosphomimetic
mutations affect kinetics of tetramer assembly and disassembly, but their effects
on tetramerization equilibrium and dNTPase activity are insignificant. In
contrast, the Y146S/Y154S dimerization-defective mutant displays a severe dNTPase
defect in vitro, but is indistinguishable from WT in its ability to deplete
cellular dNTP pools and to restrict HIV replication. Our data suggest that the
effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain
the retroviral restriction defect, and we hypothesize that enzymatic activity of
SAMHD1 is subject to additional cellular regulatory mechanisms that have not yet
been recapitulated in vitro.
PMID- 27511590
TI - Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody
positive erosive oral lichen planus patients with desquamative gingivitis.
AB - BACKGROUND/PURPOSE: Erosive oral lichen planus (EOLP) patients with desquamative
gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic.
This study assessed hematinic deficiencies and anemia statuses in antigastric
parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA+/DG+/EOLP
patients). METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and
homocysteine concentrations and serum GPCA levels in 92 GPCA+/DG+/EOLP patients
and 184 age- and sex-matched healthy controls were measured and compared between
the two groups. RESULTS: We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of
92 GPCA+/DG+/EOLP patients had hemoglobin (men < 13 g/dL and women < 12 g/dL),
iron (< 60 MUg/dL), and vitamin B12 (< 200 pg/mL) deficiencies, respectively.
Moreover, 37 (40.2%) of 92 GPCA+/DG+/EOLP patients had an abnormally high blood
homocysteine level (> 12.1MUM). GPCA+/DG+/EOLP patients had a significantly
higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally
high blood homocysteine level than healthy control individuals (all p < 0.001).
Of 27 anemic GPCA+/DG+/EOLP patients, 13 (48.2%) had pernicious anemia, five
(18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the
remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA+/DG+/EOLP
patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had
pernicious anemia. CONCLUSION: We conclude that GPCA+/DG+/EOLP patients may have
vitamin B12 deficiency, iron deficiency, and an abnormally high blood
homocysteine level. In addition to pernicious anemia, GPCA+/DG+/EOLP patients may
sometimes have normocytic anemia or iron deficiency anemia.
PMID- 27511591
TI - Healthcare-Associated Infections in Pediatric and Neonatal Intensive Care Units:
Impact of Underlying Risk Factors and Antimicrobial Resistance on 30-Day Case
Fatality in Italy and Brazil.
AB - OBJECTIVES To describe trends in the epidemiology of healthcare-associated
Infections (HAIs) in pediatric/neonatal intensive care units (ICUs) and to
evaluate risk factors and impact of multidrug resistance in children admitted to
ICUs. DESIGN Multicenter, retrospective, cohort study with a nested case-control
study conducted from January 1, 2010, through December 31, 2014. SETTING Three
tertiary care pediatric hospitals in Italy and Brazil with a total of 103 ICU
beds. PATIENTS Inclusion criteria were admission to ICU during the study period,
age at onset less than 18 years, and microbiologically confirmed HAI. RESULTS A
total of 538 HAIs in 454 children were included; 93.3% of patients had
comorbidities. Bloodstream infections were the leading pattern (45.4%). The
cumulative incidence of HAI was 3.6/100 ICU admissions and the crude 30-day
fatality rate was 5.7/1,000 admissions. The most frequently isolated pathogens
were Enterobacteriaceae, followed by Pseudomonas aeruginosa and Staphylococcus
aureus. Forty-four percent of isolates were multidrug-resistant (MDR). Two
multivariate logistic regressions were performed. Factors independently
associated with an MDR-HAI were country, previous antibiotics, transplantation,
major surgery, and colonization by an MDR strain. Factors independently
associated with 30-day case fatality were country, previous transplantation,
fungal infection, bloodstream infection, lower respiratory tract infection, and
infection caused by MDR strains. CONCLUSIONS Infection control and prevention can
limit the spread of MDR strains and improve outcomes. Targeted surveillance
programs collecting neonatal and pediatric HAI/bloodstream infection data and
outcomes would allow global benchmarking. The next step is to identify methods to
monitor key HAIs and integrate these into affordable intervention programs.
Infect Control Hosp Epidemiol 2016;1-8.
PMID- 27511592
TI - Efficacy of fluralaner in 17 dogs with sarcoptic mange.
AB - BACKGROUND: There are few licensed options for the treatment of canine sarcoptic
mange. OBJECTIVE: To evaluate the efficacy of fluralaner in dogs with sarcoptic
mange infestation. ANIMALS: Seventeen dogs with a diagnosis of Sarcoptes scabiei
based on positive skin scrapings. METHODS: A single dose of oral fluralaner was
administered according to the manufacturer's instructions. Assessments of
pruritus and lesions were performed every 7 days for 1 month. RESULTS: By Day 14
post-treatment, skin scrapings from all dogs were negative for mites. At the
beginning of the study there was a negative correlation between body weight of
the subject and pruritus [Pearson correlation coefficient (PCC) = -0.396, P =
0.007] and a positive correlation between pruritus and lesion severity (PCC
0.755, P = 0.0001). Significant decreases in lesion size and pruritus were
observed within the first 14-21 days, respectively, and improvement in these
parameters continued until the end of the study at Day 28. CONCLUSION: Fluralaner
was effective in eliminating scabies mites within 14 days and significantly
resolved the clinical signs associated with sarcoptic mange within 21 days after
a single dose.
PMID- 27511593
TI - Human antibody recognition of xenogeneic antigens (NeuGc and Gal) on porcine
heart valves: could genetically modified pig heart valves reduce structural valve
deterioration?
AB - BACKGROUND: Glutaraldehyde-fixed bioprosthetic heart valves (GBHVs) derived from
wild-type (WT, genetically unmodified) pigs are widely used clinically for heart
valve replacement. There is evidence that their failure is related to an immune
response. The use of valves from genetically engineered pigs that do not express
specific pig antigens may prolong GBHV survival. Our aims were to determine (i)
expression of Gal and NeuGc on heart (aortic and pulmonary) valves and
pericardium of WT, alpha1,3-galactosyltransferase gene knockout (GTKO) and GTKO/N
glycolylneuraminic acid gene-knockout (GTKO/NeuGcKO) pigs in comparison with
three different commercially available GBHVs and (ii) to determine human antibody
binding to these tissues. METHODS: Wild-type, GTKO/CD46, and GTKO/CD46/NeuGcKO
pig valves and pericardium were tested (i) fresh and (ii) after fixation with
glutaraldehyde (0.02%, 0.2%, 2%). Sections of GBHVs, fresh and fixed valves, and
pericardium were stained for Gal and NeuGc expression, and for human IgM and IgG
antibody binding. RESULTS: Gal and NeuGc expression was high on all GBHVs and WT
pig valves/pericardium, but was absent after antigen-specific-knockout. There was
no difference in antigen expression or antibody binding among WT aortic,
pulmonary valves, and pericardium as well as GBHVs. Glutaraldehyde fixation did
not alter expression of Gal or NeuGc. After incubation with human serum, human
IgM and IgG bound to all GBHVs and WT pig valves/pericardium. Valves from
GTKO/CD46 pigs and, particularly, GTKO/CD46/NeuGcKO pigs (with/without
glutaraldehyde fixation) showed less IgM and IgG binding. CONCLUSION: Compared to
WT pigs, GTKO/CD46/NeuGcKO pigs would be preferable sources of GBHVs, because the
absence of Gal/NeuGc expression reduces human antibody binding.
PMID- 27511594
TI - Comparison and Evaluation of the Effectiveness of Two Approaches of Diffusible
Iodine-Based Contrast-Enhanced Computed Tomography (diceCT) for Avian Cephalic
Material.
AB - Diffusible iodine-based contrast-enhanced computed tomography presents a
comparatively new tool kit for imaging fine-scale three-dimensional phenotypes
that is rapidly becoming standard anatomical practice. However, relatively few
studies have attempted to look at subtle differences in staining protocols or
attempted to model tissue reactions to gain insight into staining mechanisms.
Here, two iodine-based contrast agents, iodine-ethanol (I2 E) and iodine
potassium iodide (I2 KI) in neutral buffered formalin , were applied to avian
cephalic specimens to investigate their effectiveness. We found that the two
solutions had markedly different results for staining of mineralized skeletal
tissues (i.e., bone). Other tissues, including muscles, epithelia, and common
connective tissues (e.g., lamina propria) were assessed individually and show
minor differences in the sorption of iodine. Numerical simulations suggest that
different results from I2 E and I2 KI-formaldehyde staining are due to different
partition coefficients and retardation factors of tissues, fixation effects, as
well as distinct iodine diffusion and sorption patterns. We found a clear
positive relationship between glycogen concentration and grayscale values
measured within muscle, epithelia, nervous tissues, and glands. We also found the
use of ethanol for tissue fixation and following I2 E staining outperforms I2 KI
formaldehyde by providing higher efficiency for acquiring greater contrast both
between different soft tissues and between mineralized and nonmineralized
tissues.
PMID- 27511595
TI - Effects of perfluorinated alkyl acids on cellular responses of MCF-10A mammary
epithelial cells in monolayers and on acini formation in vitro.
AB - Perfluorinated alkyl acids (PFAAs) are stable chemicals detected in tissue and
serum from various species, including humans, and have been linked to adverse
health outcomes. Experimental PFAA exposure in rodents has been associated with
changes in mammary gland development. The estrogen receptor (ER)-negative human
breast epithelial cell line, MCF-10A, can be grown as monolayer, but also has the
ability to form three-dimensional acini in vitro, reflecting aspects of mammary
glandular morphogenesis. Cells were exposed to five different PFAAs,
perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA),
perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and
perfluoroundecanoic acid (PFUnDA), both in monolayer and acini cultures. In
monolayer cultures only the higher concentrations of PFOS, PFNA and PFDA (400
500MUM) caused a significant increase in cell death, whereas PFOA and PFUnDA had
no effect. Normal acini maturation was negatively impacted by PFOS, PFNA and PFDA
already at the lowest concentration tested (0.6MUM). Observed effects included
loss of organization of the cell clusters and absence of a hollow lumen. Overall,
this study demonstrated that PFAAs can interfere with cellular events related to
normal development of glandular breast tissue through ER-independent mechanisms.
PMID- 27511596
TI - Arthroscopic irrigation of the bovine stifle joint increases cartilage surface
friction and decreases superficial zone lubricin.
AB - The purpose of this study was to determine the effects of arthroscopic irrigation
on cartilage superficial zone lubricin and surface friction. Arthroscopic partial
meniscectomy is one of the most commonly performed orthopedic surgeries in the
United States, but rates of osteoarthritis progression following this procedure
are high. The effect of arthroscopic irrigation on articular surface lubrication
has not been previously considered as a contributing factor in outcomes after
arthroscopy. Fourteen bovine stifle joints were randomized to receive
arthroscopic irrigation (n=7) or no treatment (n=7). Full-thickness osteochondral
explants from these joints underwent friction testing to measure static and
dynamic coefficients of friction. Following mechanical testing, samples were
fixed and stained for lubricin. Percent integrated density, a measure of the
amount of lubricin in the superficial zone (0-100um depth), was determined.
Static and dynamic coefficients of friction were found to be significantly
greater in arthroscopy specimens compared to controls (p=0.02 and p<0.001,
respectively). Percent integrated density of lubricin in the superficial zone was
significantly lower in arthroscopy specimens compared to controls (p<0.001).
PMID- 27511597
TI - Mechanisms influencing retrograde flow in the atrioventricular canal during early
embryonic cardiogenesis.
AB - Normal development of the heart is regulated, in part, by mechanical influences
associated with blood flow during early stages of embryogenesis. Specifically,
the potential for retrograde flow at the atrioventricular canal (AVC) is
particularly important in valve development. However, the mechanisms causing this
retrograde flow have received little attention. In this study, a numerical
analysis was performed on images of the embryonic zebrafish heart between 48 and
55hpf. During these stages, normal retrograde flow is prevalent. To manipulate
this flow, zebrafish were placed in a centrifuge and subjected to a hypergravity
environment to alter the cardiac preload at various six-hour intervals between 24
and 48hpf. Parameters of the pumping mechanics were then analyzed through a
spatiotemporal analysis of processed image sequences. We find that the loss of
retrograde flow in experimentally manipulated embryos occurs in part because of a
greater resistance in the form of atrial and AVC contractile closure.
Additionally, during retrograde flow, these embryos exhibit significantly greater
pressure difference across the AVC based on calculations of expansive and
contractile rates of the atrium and ventricle. These results elucidated that the
developing heart is highly sensitive to small changes in pumping mechanics as it
strives to maintain normal hemodynamic conditions necessary for later cardiac
development.
PMID- 27511598
TI - Review of bioanalytical assays for the quantitation of various HDAC inhibitors
such as vorinostat, belinostat, panobinostat, romidepsin and chidamine.
AB - Histone deacetylase inhibitors (HDAC inhibitors) are used to treat malignancies
such as cutaneous T cell lymphoma and peripheral T cell lymphoma. Only four drugs
are approved by the US Food and Drug Administration, namely vorinostat,
romidepsin, panobinostat and belinostat, while chidamide has been approved in
China. There are a number of bioanalytical methods reported for the measurement
of HDAC inhibitors in clinical (human plasma and serum) and preclinical (mouse
plasma, rat plasma, urine and tissue homogenates, etc.) studies. This review
covers various HDAC inhibitors such as vorinostat, romidepsin, panobinostat,
belinostat and chidamide. In addition to providing a comprehensive review of the
available methods for the above mentioned HDAC inhibitors, it also provides case
studies with perspectives for chosen drugs. Based on the review, it is concluded
that the published methodologies using either HPLC or LC-MS/MS are well suited
for the quantification of HDAC inhibitors in various biological fluids to
delineate pharmacokinetic data.
PMID- 27511599
TI - Natural Products at Work: Structural Insights into Inhibition of the Bacterial
Membrane Protein MraY.
AB - Natural(ly) fit: The X-ray crystal structure of the bacterial membrane protein
MraY in complex with its natural product inhibitor muraymycin D2 is discussed.
MraY catalyzes one of the membrane-associated steps in peptidoglycan biosynthesis
and, therefore, represents a promising target for novel antibiotics. Structural
insights derived from the protein-inhibitor complex might now pave the way for
the development of new antimicrobial drugs.
PMID- 27511600
TI - The Associations of HLA-A*02:01 and DRB1*11:01 with Hepatitis C Virus Spontaneous
Clearance Are Independent of IL28B in the Chinese Population.
AB - Spontaneous clearance of hepatitis C virus (HCV) occurs in 10-40% of the
infections. Specific human leukocyte antigen (HLA) alleles have been identified
in associating with HCV clearance. However, data on the association of HLA with
the spontaneous clearance of HCV are scarce in the Chinese population. In the
current study we studied the HLA class I and class II genes in 231 Chinese
voluntary blood donors who had cleared HCV infection spontaneously compared to
429 subjects with chronic HCV infections. We also studied their IL28B SNP
(rs8099917) genotype, since a number of investigators have found a strong
association of IL28B with spontaneous or treatment induced HCV clearance. We
found that HLA-A*02:01 and DQB1*05:02 distributed differently between the two
groups after Bonferroni correction (odds ratio [OR] = 1.839, Pc = 0.024 and OR =
0.547, Pc = 0.016, respectively). Multivariate logistic regression analysis
suggested that A*02:01 and DRB1*11:01 (OR = 1.798, P = 0.008 and OR = 1.921, P =
0.005, respectively) were associated with HCV spontaneous clearance, independent
of age, gender and IL28B polymorphism. We concluded that in the Chinese
population, HLA-A*02:01 and DRB1*11:01 might be associated with the host capacity
to clear HCV independent of IL28B, which suggesting that the innate and adaptive
immune responses both play an important role in the control of HCV.
PMID- 27511602
TI - Blue-sky bifurcation of ion energies and the limits of neutral-gas sympathetic
cooling of trapped ions.
AB - Sympathetic cooling of trapped ions through collisions with neutral buffer gases
is critical to a variety of modern scientific fields, including fundamental
chemistry, mass spectrometry, nuclear and particle physics, and atomic and
molecular physics. Despite its widespread use over four decades, there remain
open questions regarding its fundamental limitations. To probe these limits, here
we examine the steady-state evolution of up to 10 barium ions immersed in a gas
of three-million laser-cooled calcium atoms. We observe and explain the emergence
of nonequilibrium behaviour as evidenced by bifurcations in the ion steady-state
temperature, parameterized by ion number. We show that this behaviour leads to
the limitations in creating and maintaining translationally cold samples of
trapped ions using neutral-gas sympathetic cooling. These results may provide a
route to studying non-equilibrium thermodynamics at the atomic level.
PMID- 27511601
TI - Age-dependent increase in the expression of antioxidant-like protein-1 in the
gerbil hippocampus.
AB - Antioxidant-like protein-1 (AOP-1) reduces the intracellular level of reactive
oxygen species. In the present study, the age-related change in AOP-1 expression
in the hippocampus among young, adult and aged gerbils was compared using western
blot analysis and immunohistochemistry. The results demonstrated that the protein
expression of AOP-1 was gradually and significantly increased in the hippocampus
during the normal aging process. In addition, the age-dependent increase in AOP-1
immunoreactivity was also observed in pyramidal neurons of the hippocampus
proper; however, in the dentate gyrus, AOP-1 immunoreactivity was not altered
during the normal aging process. These results indicated that the expression of
AOP-1 is significantly increased in the hippocampus proper, but not in the
dentate gyrus, during the normal aging process.
PMID- 27511604
TI - Reply.
PMID- 27511603
TI - PRDM16 is associated with evasion of apoptosis by prostatic cancer cells
according to RNA interference screening.
AB - Histone methylation, which is regulated by histone methyltransferases (HMTs) and
histone demethylases (HDMs), has been indicated to be involved in a variety of
diseases, particularly in cancer, including androgen-independent prostate cancer
(PCa). However, the functions of HMTs and HDTs in cancer have largely remained
elusive. The present study, utilized an RNA interference screening using a
lentiviral small hairpin (sh)RNA library to systematically elucidate the function
of HMTs and HDTs in PCa cell growth and viability. Nine HMTs and HDTs, namely
FBXO11, PRDM10, JMJD8, MLL, SETD4, JMJD7, PRMT2, MEN1 and PRDM16, were identified
to affect DU145 cell viability, as indicated by an MTS assay subsequent to
knockdown of the specific genes using shRNA pools. Furthermore, flow cytometric
analysis and western blot analysis of apoptosis-associated proteins indicated
that PRDM16 has an anti-apoptotic role in PCa cells. In addition, the spliced
form, sPRDM16/MEL1S, was detected to be overexpressed in PCa cell lines. In
conclusion, the present study indicated an important oncogenic role of
sPRDM16/MEL1S in PCa and suggested that PRDM16 may represent a novel therapeutic
target.
PMID- 27511605
TI - Nomenclature for factors of the HLA system, update April 2016.
PMID- 27511606
TI - Temporal and spectral properties of esophageal mucosal blood perfusion: a
comparison between normal subjects and nutcracker esophagus patients.
AB - BACKGROUND: The mechanism of esophageal pain in patients with nutcracker
esophagus (NE) and other esophageal motor disorders is not known. Our recent
study shows that baseline esophageal mucosal perfusion, measured by laser Doppler
perfusion monitoring, is lower in NE patients compared to controls. The goal of
our current study was to perform a more detailed analysis of esophageal mucosal
blood perfusion (EMBP) waveform of NE patients and controls to determine the
optimal EMBP biomarkers that combined with suitable statistical learning models
produce robust discrimination between the two groups. METHODS: Laser Doppler
recordings of 10 normal subjects (mean age 43 +/- 15 years, 8 males) and 10
patients (mean age 47 +/- 5.5 years., 8 males) with NE were analyzed. Time and
frequency domain features were extracted from the first twenty-minute recordings
of the EMBP waveforms, statistically ranked according to four independent
evaluation criterions, and analyzed using two statistical learning models,
namely, logistic regression (LR) and support vector machines (SVM). KEY RESULTS:
The top three ranked predictors between the two groups were the 0.5 and 0.75
perfusion quantile values followed by the surface of the EMBP power spectrum in
the frequency domain. ROC curve ranking produced a cross-validated AUC (area
under the curve) of 0.93 for SVM and 0.90 for LR. CONCLUSIONS & INFERENCES: We
show that as a group NE patients have lower perfusion values compared to
controls, however, there is an overlap between the two groups, suggesting that
not all NE patients suffer from low mucosal perfusion levels.
PMID- 27511607
TI - Improving Team Performance for Public Health Preparedness.
AB - OBJECTIVE: Between May 2010 and September 2011, the University of Minnesota
School of Public Health partnered with the Minnesota Department of Health (MDH)
to assess the effect of exercises on team performance during public health
emergency response. METHODS: Participants were divided into 3 research teams
exposed to various levels of intervention. Groups consisted of a control group
that was given standard MDH training exercises, a didactic group exposed to team
dynamics and communication training, and a treatment group that received the
didactic training in addition to a post-exercise facilitated debriefing. To
assess differences in team performance, teams engaged in 15 functional exercises.
RESULTS: Differences in team performance across the 3 groups were identified,
although there was no trend in team performance over time for any of the groups.
Groups demonstrated fluctuation in team performance during the study period.
Attitudinal surveys demonstrated an increase in workplace satisfaction and
confidence in training among all groups throughout the study period. CONCLUSIONS:
Findings from this research support that a critical link exists between training
type and team performance during public health emergency response. This research
supports that intentional teamwork training for emergency response workers is
essential for effective public health emergency response. (Disaster Med Public
Health Preparedness. 2017;11:7-10).
PMID- 27511608
TI - Metabolic syndrome and psoriasis severity in South-East Asian patients: An
investigation of potential association using current and chronological
assessments.
AB - Although studies regarding prevalence of metabolic syndrome (MS) in Asian
psoriatic patients are limited and show varying results, a previous report
describes a significant increase in prevalence of MS in Thai psoriatic patients,
as compared with rates in the general population. However, no significant
association between MS and psoriasis severity using the Psoriasis Area and
Severity Index (PASI) was found, which differs from the findings of Korean and
Japanese studies. This study aimed at re-evaluating the association between MS
and psoriasis severity in Thai patients using current assessment (PASI) and
chronological assessment (historical course and interventions). A total of 273
psoriatic patients were recruited. After controlling for age and sex, 96 patients
were assigned to the MS group and 96 patients to the non-MS group. Similar to the
previous study, no significant differences were identified between metabolic and
non-metabolic patients regarding PASI, age of onset, disease duration and family
history of psoriasis. However, the numbers of hospitalizations (P = 0.018) and
interventions (P = 0.028) were significantly higher in metabolic patients than in
non-metabolic patients. Further, a greater number of metabolic components was
significantly associated with a higher number of hospitalizations (P = 0.012),
pustular or erythrodermic psoriasis episodes (P = 0.049), and interventions (P =
0.005). Body mass index of 23 kg/m2 or more, abdominal obesity and high blood
pressure were associated with an increased risk of treatment failure. Using
chronological assessment, our study supported that MS negatively affects
psoriasis severity and treatment outcomes. Screening for MS is highly recommended
for psoriatic patients.
PMID- 27511609
TI - Emotional Modulation of Conflict Processing in the Affective Domain: Evidence
from Event-related Potentials and Event-related Spectral Perturbation Analysis.
AB - Previous studies have revealed the impact of emotion on conflict processing. The
present study was conducted to investigate whether cognitive control in the
affective domain is also affected by emotion. Emotional face-word and body-word
Stroop tasks were explored and contrasted, and both behavioural and
electrophysiological measures were recorded. Behavioural results showed that both
tasks replicated previous robust interference effects. At the physiological
level, the two tasks showed dissociable neural activity in the early attention
and perception stages. It was also found that the face-word task evoked more
pronounced N1 and P2 amplitudes than the body-word task. However, the two tasks
evoked comparable N450 amplitudes. At later processing stages, positive slow
potentials were modulated by target emotion and congruency. In addition, time
frequency analyses also revealed that the face-word task induced enhanced theta
activity compared to the body-word task at both early and later stages of
processing. The present findings provide support for the dual competition
framework and suggest the dynamic modulation of emotion on cognitive control in
the affective domain.
PMID- 27511610
TI - RAMPred: identifying the N(1)-methyladenosine sites in eukaryotic transcriptomes.
AB - N(1)-methyladenosine (m(1)A) is a prominent RNA modification involved in many
biological processes. Accurate identification of m(1)A site is invaluable for
better understanding the biological functions of m(1)A. However, limitations in
experimental methods preclude the progress towards the identification of m(1)A
site. As an excellent complement of experimental methods, a support vector
machine based-method called RAMPred is proposed to identify m(1)A sites in H.
sapiens, M. musculus and S. cerevisiae genomes for the first time. In this
method, RNA sequences are encoded by using nucleotide chemical property and
nucleotide compositions. RAMPred achieves promising performances in jackknife
tests, cross cell line tests and cross species tests, indicating that RAMPred
holds very high potential to become a useful tool for identifying m(1)A sites.
For the convenience of experimental scientists, a web-server based on the
proposed model was constructed and could be freely accessible at
http://lin.uestc.edu.cn/server/RAMPred.
PMID- 27511611
TI - A comparison of questionnaires for assessing physical function in patients with
lower extremity bone metastases.
AB - OBJECTIVES: To assess, (i) the degree to which the: PROMIS Physical Function
Cancer, PROMIS Neuro-QoL Mobility, Toronto Extremity Salvage Score (TESS), Lower
Extremity Function Score (LEFS), and Musculoskeletal Tumor Society score (MSTS),
measure physical function; (ii) differences in coverage and reliability; and
(iii) difference in completion time. METHODS: One hundred of 115 (87%) patients
with lower extremity metastases participated in this prospective study. We used
exploratory factor analysis-correlating questionnaires with an underlying trait
to assess if questionnaires measure the same. Coverage was assessed by floor and
ceiling effect and reliability by the standard error of measurement (SEM).
Completion time was compared using the Friedman test. RESULTS: All questionnaires
measured the same concept; demonstrated by high correlations (>0.7). Floor effect
was absent, while ceiling effect was present in all, but highest for the PROMIS
Neuro-QoL Mobility (7%). The SEM was below the threshold-indicating reliability
over a wide range of ability levels for the PROMIS-Physical Function, TESS, and
LEFS. Completion time differed between questionnaires (P < 0.001) and was
shortest for the PROMIS questionnaires. CONCLUSIONS: The PROMIS Physical Function
is the most useful questionnaire. This is due to its reliability over a wide
range of ability levels, validity, brevity, and good coverage. J. Surg. Oncol.
2016;114:691-696. (c) 2016 Wiley Periodicals, Inc.
PMID- 27511613
TI - Blood pressure variability and cardiovascular risk.
PMID- 27511612
TI - Taking mHealth Forward: Examining the Core Characteristics.
AB - The emergence of mobile health (mHealth) offers unique and varied opportunities
to address some of the most difficult problems of health. Some of the most
promising and active efforts of mHealth involve the engagement of mobile phone
technology. As this technology has spread and as this technology is still
evolving, we begin a conversation about the core characteristics of mHealth
relevant to any mobile phone platform. We assert that the relevance of these
characteristics to mHealth will endure as the technology advances, so an
understanding of these characteristics is essential to the design,
implementation, and adoption of mHealth-based solutions. The core characteristics
we discuss are (1) the penetration or adoption into populations, (2) the
availability and form of apps, (3) the availability and form of wireless
broadband access to the Internet, and (4) the tethering of the device to
individuals. These collectively act to both enable and constrain the provision of
population health in general, as well as personalized and precision individual
health in particular.
PMID- 27511614
TI - The light-matter interaction of a single semiconducting AlGaN nanowire and noble
metal Au nanoparticles in the sub-diffraction limit.
AB - Near field scanning optical microscopy (NSOM) is not only a tool for imaging of
sub-diffraction limited objects but also a prominent characteristic tool for
understanding the intrinsic properties of nanostructures. In order to understand
light-matter interactions in the near field regime using a NSOM technique with an
excitation of 532 nm (2.33 eV), we selected an isolated single semiconducting
AlGaN nanowire (NW) of diameter ~120 nm grown via a vapor liquid solid (VLS)
mechanism along with a metallic Au nanoparticle (NP) catalyst. The role of
electronic transitions from different native defect related energy states of
AlGaN is discussed in understanding the NSOM images for the semiconducting NW.
The effect of strong surface plasmon resonance absorption of an excitation laser
on the NSOM images for Au NPs, involved in the VLS growth mechanism of NWs, is
also observed.
PMID- 27511615
TI - Congenital abnormalities in newborns of women with pregestational diabetes: A
time-trend analysis, 1994 to 2009.
AB - BACKGROUND: The main objective of the current study is to examine the trend of
congenital abnormalities among children born by women with and without diabetes,
and to explore the impact of food fortification by folic acid on the rate of
birth defects among these two groups of mothers. METHODS: All children born alive
in Ontario, Canada, during 1994 to 2009 and their mothers were included in study.
Diagnosis of pregestational diabetes among mothers was identified using Diabetes
registry, and diagnosis of birth defects among children were identified using
hospital records. RESULTS: The prevalence of births among diabetic mothers
increased by almost 200% during the study period. Among children born to mothers
with diabetes, the prevalence for all anomalies combined was approximately 47%
higher and for various cardiac and central nervous system anomalies up to a three
to fivefold higher than those born to nondiabetic mothers. While the rate of
birth defects in both groups observed a considerable decline after food
fortification in 1999, but the gap between two groups remained unchanged over
time. CONCLUSION: While the prevalence of birth defects among diabetic
pregnancies is still considerably higher that nondiabetic pregnancies, results of
the current study indicate a declining trend in the prevalence of some congenital
abnormalities among babies born to both diabetic and nondiabetic mothers after
1999. We need to be more aggressive in implementing preventive measures,
including a national diabetes plan or the proposed universal policy of supra
dietary folic acid supplementation for women with diabetes who are of
reproductive age. Birth Defects Research (Part A) 106:831-839, 2016. (c) 2016
Wiley Periodicals, Inc.
PMID- 27511616
TI - The effect of environmental contamination on the community structure and
fructification of ectomycorrhizal fungi.
AB - Ectomycorrhizal fungi are an essential component of forest ecosystems, most of
which can form edible and medical fruiting bodies. Although many studies have
focused on the fructification of ectomycorrhizal fungi in phenology, the impact
of environmental contamination, especially living garbage, on the formation of
fruiting body is still unknown. A field investigation, combined with a high
throughput sequencing method, was used to study the effect of living garbage
pollution on the fructification and hypogeous community structure of
ectomycorrhizal fungi symbiosing with cedar (Cedrus deodara (Roxb.) G. Don). The
results showed that garbage significantly altered soil abiotic and biotic
properties, increasing soil urease activity, decreasing the soil exchangeable
metal content and phosphatase activity, and ultimately inhibiting the formation
of fruiting bodies. The pollution of garbage also changed the community structure
of hypogeous ectomycorrhizal fungi where ectomycorrhizal ascomycetes dominated.
In unpolluted sites, the relative abundance of ectomycorrhizal ascomycetes and
basidiomycetes were almost equal. Although no fruiting bodies were observed in
that soil polluted by living garbage, the sequencing result showed that various
ectomycorrhizal fungi were present underground, suggesting that these taxonomic
fungi had the potential to cope with adverse conditions. This study not only
provided a deeper understanding of the relationship between ectomycorrhizal
fungal communities and prevailing environmental conditions, but provided a new
pathway for the excavation and utilization of the resource of antistress
ectomycorrhizal fungi.
PMID- 27511617
TI - Barriers and facilitators to health screening in men: A systematic review.
AB - RATIONALE: Men have poorer health status and are less likely to attend health
screening compared to women. OBJECTIVE: This systematic review presents current
evidence on the barriers and facilitators to engaging men in health screening.
METHODS: We included qualitative, quantitative and mixed-method studies
identified through five electronic databases, contact with experts and reference
mining. Two researchers selected and appraised the studies independently. Data
extraction and synthesis were conducted using the 'best fit' framework synthesis
method. RESULTS: 53 qualitative, 44 quantitative and 6 mixed-method studies were
included. Factors influencing health screening uptake in men can be categorized
into five domains: individual, social, health system, healthcare professional and
screening procedure. The most commonly reported barriers are fear of getting the
disease and low risk perception; for facilitators, they are perceived risk and
benefits of screening. Male-dominant barriers include heterosexual -self
presentation, avoidance of femininity and lack of time. The partner's role is the
most common male-dominant facilitator to screening. CONCLUSIONS: This systematic
review provides a comprehensive overview of barriers and facilitators to health
screening in men including the male-dominant factors. The findings are
particularly useful for clinicians, researchers and policy makers who are
developing interventions and policies to increase screening uptake in men.
PMID- 27511618
TI - Tailoring Size and Coverage Density of Silver Nanoparticles on Monodispersed
Polymer Spheres as Highly Sensitive SERS Substrates.
AB - Silver nanoparticles (AgNPs) were deposited onto the monodispersed carboxylic
polystyrene (CPS) spheres by an improved in situ reduction method. The size and
coverage density of the AgNPs on the surface of CPS spheres could be easily
tailored by tuning the concentrations of carboxylic functional groups and silver
precursor. The morphologies and structures of the resulting CPS/Ag hybrid
particles were studied by scanning electron microscopy (SEM), transmission
electron microscopy (TEM), X-ray diffraction (XRD), UV-Vis-NIR spectrometer and X
ray photoelectron spectroscopy (XPS), etc. The surface enhanced Raman scattering
(SERS) performances of the resulting uniform CPS/Ag hybrid particles were
investigated using 4-aminobenzenethiol (4-ABT) as the probe molecule. The
optimized CPS/Ag hybrid particles show high enhancement factor (EF) of 2.71*10(7)
, low limit of detection (LOD) of 10(-10) m and good reproducibility with
relative standard deviation (RSD) of 9.64 %. The good SERS improvement properties
demonstrate these hybrid particles could be employed as simple and effective
substrates in the SERS spectroscopy.
PMID- 27511619
TI - Systematic review of the methodological and reporting quality of case series in
surgery.
AB - BACKGROUND: Case series are an important and common study type. No guideline
exists for reporting case series and there is evidence of key data being missed
from such reports. The first step in the process of developing a methodologically
sound reporting guideline is a systematic review of literature relevant to the
reporting deficiencies of case series. METHODS: A systematic review of
methodological and reporting quality in surgical case series was performed. The
electronic search strategy was developed by an information specialist and
included MEDLINE, Embase, Cochrane Methods Register, Science Citation Index and
Conference Proceedings Citation index, from the start of indexing to 5 November
2014. Independent screening, eligibility assessments and data extraction were
performed. Included articles were then analysed for five areas of deficiency:
failure to use standardized definitions, missing or selective data (including the
omission of whole cases or important variables), transparency or incomplete
reporting, whether alternative study designs were considered, and other issues.
RESULTS: Database searching identified 2205 records. Through the process of
screening and eligibility assessments, 92 articles met inclusion criteria.
Frequencies of methodological and reporting issues identified were: failure to
use standardized definitions (57 per cent), missing or selective data (66 per
cent), transparency or incomplete reporting (70 per cent), whether alternative
study designs were considered (11 per cent) and other issues (52 per cent).
CONCLUSION: The methodological and reporting quality of surgical case series
needs improvement. The data indicate that evidence-based guidelines for the
conduct and reporting of case series may be useful.
PMID- 27511621
TI - A dialdehyde-diboronate-functionalized AIE luminogen: design, synthesis and
application in the detection of hydrogen peroxide.
AB - A dialdehyde-diboronate-functionalized tetraphenylethene (TPE-DABF) was reported
as a H2O2-specific AIE luminogen. TPE-DABF, bearing multiple reductive units
(aldehyde, boronate and fructose) in one molecule, afforded an excellent H2O2
selectivity over other ROS in biological buffer, and can be used for sensitive
detection of glucose under neutral conditions.
PMID- 27511620
TI - Value of corneal epithelial and Bowman's layer vertical thickness profiles
generated by UHR-OCT for sub-clinical keratoconus diagnosis.
AB - Ultra-high resolution optical coherence tomography (UHR-OCT) can image the
corneal epithelium and Bowman's layer and measurement the thicknesses. The
purpose of this study was to validate the diagnostic power of vertical thickness
profiles of the corneal epithelium and Bowman's layer imaged by UHR-OCT in the
diagnosis of sub-clinical keratoconus (KC). Each eye of 37 KC patients,
asymptomatic fellow eyes of 32 KC patients, and each eye of 81 normal subjects
were enrolled. Vertical thickness profiles of the corneal epithelium and Bowman's
layer were measured by UHR-OCT. Diagnostic indices were calculated from vertical
thickness profiles of each layer and output values of discriminant functions
based on individual indices. Receiver operating characteristic curves were
determined, and the accuracy of the diagnostic indices were assessed as the area
under the curves (AUC). Among all of the individual indices, the maximum ectasia
index for epithelium had the highest ability to discriminate sub-clinical KC from
normal corneas (AUC = 0.939). The discriminant function containing maximum
ectasia indices of epithelium and Bowman's layer further increased the AUC value
(AUC = 0.970) for sub-clinical KC diagnosis. UHR-OCT-derived thickness indices
from the entire vertical thickness profiles of the corneal epithelium and
Bowman's layer can provide valuable diagnostic references to detect sub-clinical
KC.
PMID- 27511622
TI - Laterality of motor cortical function measured by transcranial magnetic
stimulation threshold tracking.
AB - INTRODUCTION: Threshold tracking paired-pulse transcranial magnetic stimulation
(TTTMS) examines cortical function and is useful for diagnosis of motor neuron
disorders. Differences in cortical function have been identified between dominant
and non-dominant limbs using constant stimulus methods, but they remain unclear,
potentially due to methodological differences. In this study we aimed to clarify
differences in cortical function between dominant and non-dominant limbs using
TTTMS. METHODS: Single-pulse TMS, TTTMS, and nerve conduction studies were
performed in 25 healthy, right-handed participants by recording from the abductor
pollicis brevis muscle. RESULTS: There were no side-to-side differences observed
in resting motor threshold, motor evoked potential (MEP) amplitude, MEP latency,
central motor conduction time, cortical silent period, short-interval
intracortical inhibition and facilitation, compound muscle action potential
(CMAP) amplitude, CMAP latency, F-wave latency, or neurophysiological index.
CONCLUSIONS: These findings suggest that, when using TTTMS, there are no
differences in cortical function between dominant and non-dominant hemispheres.
Muscle Nerve 55: 424-427, 2017.
PMID- 27511623
TI - Bio-Inspired Design and Fabrication of Micro/Nano-Brush Dual Structural Surfaces
for Switchable Oil Adhesion and Antifouling.
AB - The underwater superoleophobic surfaces play a significant role in anti-oil
contamination, marine antifouling, etc. Inspired by the Gecko's feet and its self
cleaning property, a hierarchical structure composed of poly (acrylic acid) gel
micro-brushes is designed by the liquid-infused method. This surface exhibits
underwater superoleophobicity with very low oil adhesion. It is then modified
with stimuli-responsive polymer nano-brushes via surface-initiated atom transfer
radical polymerization from the embedded initiator. The micro/nano-brush dual
structural surfaces can switch the underwater oil adhesion between low and high
while keeping the superoleophobicity. The antifouling properties against algae
attachment under different mediums are also investigated to show a strong link
between oleophobicity and antibiofouling property. The model surface will be very
useful in directing the design of marine self-cleaning coatings to both living
and non-living species.
PMID- 27511625
TI - Concordance of poor child feeding and preventive behavior and its predictors in
southwest rural Ethiopia.
AB - BACKGROUND: Inappropriate child feeding and caring practices are a major cause of
malnutrition. To date, no studies have examined concordance and discordance of
child feeding and preventive behavior and their predictors in developing
countries. METHODS: We used baseline data generated from A 2-year-longitudinal
agriculture-nutrition panel survey conducted from February 9 to April 9, 2014, in
nine districts encompassing 20 randomly selected counties in Oromiya Region and
Southern Nation, Nationality and Peoples Region in Ethiopia. Households were
recruited using the Expanded Program on Immunization sampling method. A total of
623 children under the age of 5 years and their respective caregivers were
included in the analyses. Generalized estimating equations were used to account
for clustered observations. RESULTS: Concordance of poor child feeding and
preventive behavior was observed in 45.1% of the children, while 45.5% of the
children were suffering from discordance of poor child feeding and preventive
behavior. Concordance and discordance of poor child feeding and preventive
behavior had almost different predictors. Concordance of poor child feeding and
preventive behavior was significantly associated with the age of the caretaker of
>=40 years (odds ratio (OR)=2.14; 95% confidence interval (CI): 1.04, 4.41), low
household dietary diversity (OR=3.69; 95% CI: 1.93, 7.04), medium household
dietary diversity (OR=2.17; 95% CI: 1.17, 4.00), severe household food insecurity
(OR=1.72; 95% CI: 1.01, 2.93), and increase with increasing child age.
CONCLUSION: A substantial number of children in the southwest of rural Ethiopia
are exposed to both poor child feeding and preventive behavior. Low household
dietary diversity and extreme food insecurity household were predictors of
concordance of poor child feeding and poor preventive behavior and provide useful
entry points for comprehensive interventions to address child feeding and caring
in the area.
PMID- 27511624
TI - Ribonucleotides and Transcription-Associated Mutagenesis in Yeast.
AB - High levels of transcription stimulate mutation rates in microorganisms, and this
occurs primarily through an enhanced accumulation of DNA damage. The major source
of transcription-associated damage in yeast is Topoisomerase I (Top1), an enzyme
that removes torsional stress that accumulates when DNA strands are separated.
Top1 relieves torsional stress by nicking and resealing one DNA strand, and some
Top1-dependent mutations are due to trapping and processing of the covalent
cleavage intermediate. Most, however, reflect enzyme incision at ribonucleotides,
which are the most abundant noncanonical component of DNA. In either case, Top1
generates a distinctive mutation signature composed of short deletions in tandem
repeats; in the specific case of ribonucleotide-initiated events, mutations
reflect sequential cleavage by the enzyme. Top1-dependent mutations do not
require highly activated transcription, but their levels are greatly increased by
transcription, which partially reflects an interaction of Top1 with RNA
polymerase. Recent studies have demonstrated that Top1-dependent mutations
exhibit a strand bias, with the nature of the bias differing depending on the
transcriptional status of the underlying DNA. Under low-transcription conditions,
most Top1-dependent mutations arise in the context of replication and reflect
incision at ribonucleotides incorporated during leading-strand synthesis. Under
high-transcription conditions, most Top1-dependent events arise when the enzyme
cleaves the non-transcribed strand of DNA. In addition to increasing genetic
instability in growing cells, Top1 activity in transcriptionally active regions
may be a source of mutations in quiescent cells.
PMID- 27511626
TI - Enhancement of active MMP release and invasive activity of lymph node metastatic
tongue cancer cells by elevated signaling via the TNF-alpha-TNFR1-NF-kappaB
pathway and a possible involvement of angiopoietin-like 4 in lung metastasis.
AB - To study the role of TNF-alpha in tongue cancer metastasis, we made highly
metastatic cells from a human oral squamous cell carcinoma cell line (SAS) by
repeating the passage in which the cells were injected into a nude mouse tongue
and harvested from metastasized cervical lymph nodes. Cancer cells after 5
passages (GSAS/N5) increased invasive activity 7-fold in a TNF-alpha receptor 1
(TNFR1)-dependent manner and enhanced mRNA expression of TNF-alpha and TNFR1. In
the highly metastatic cells, NF-kappaB activation was upregulated via elevated
phosphorylation of Akt and Ikkalpha/beta in the signaling pathway and secretion
of TNF-alpha, active MMP-2 and MMP-9 increased. Suppression of increase of TNF
alpha mRNA expression and MMP secretion by NF-kappaB inhibitor NBD peptide
suggested a positive feedback loop in GSAS/N5 cells; TNF-alpha activates NF
kappaB and activated NF-kappaB induces further TNF-alpha secretion, leading to
increase of active MMP release and promotion of invasion and metastasis of the
cells. GSAS/N5 cells that had been injected into the nude mouse tongue and
harvested from metastasized lungs multiplied angiopoietin-like 4 (angptl4)
expression with enhanced migration activity, which indicated a possible
involvement of angptl4 in lung metastasis of the cells. These results suggest
that TNF-alpha and angptl4 promote metastasis of the oral cancer cells, thus,
these molecules may be therapeutic targets for patients with tongue cancer.
PMID- 27511628
TI - Unexpected functions of automatically annotated genes: a lesson learnt from
Bacillus subtilis.
PMID- 27511627
TI - Age-related differences in autism: The case of white matter microstructure.
AB - Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in
which white matter abnormalities are already present early on in life. However,
it is unknown if and to which extent these abnormalities are hard-wired in
(older) adults with ASD and how this interacts with age-related white matter
changes as observed in typical aging. The aim of this first cross-sectional study
in mid- and late-aged adults with ASD was to characterize white matter
microstructure and its relationship with age. We utilized diffusion tensor
imaging with head motion control in 48 adults with ASD and 48 age-matched
controls (30-74 years), who also completed a Flanker task. Intra-individual
variability of reaction times (IIVRT) measures based on performance on the
Flanker interference task were used to assess IIVRT-white matter microstructure
associations. We observed primarily higher mean and radial diffusivity in white
matter microstructure in ASD, particularly in long-range fibers, which persisted
after taking head motion into account. Importantly, group-by-age interactions
revealed higher age-related mean and radial diffusivity in ASD, in projection and
association fiber tracts. Subtle dissociations were observed in IIVRT-white
matter microstructure relations between groups, with the IIVRT-white matter
association pattern in ASD resembling observations in cognitive aging. The
observed white matter microstructure differences are lending support to the
structural underconnectivity hypothesis in ASD. These reductions seem to have
behavioral percussions given the atypical relationship with IIVRT. Taken
together, the current results may indicate different age-related patterns of
white matter microstructure in adults with ASD. Hum Brain Mapp 38:82-96, 2017.
(c) 2016 Wiley Periodicals, Inc.
PMID- 27511629
TI - The Bindex((r)) ultrasound device: reliability of cortical bone thickness
measures and their relationship to regional bone mineral density.
AB - The Bindex((r)) quantitative ultrasound (QUS) device is currently available and
this study analyzed (I) its relative and absolute intra- and inter-session
reliability and (II) the relationship between the data provided by Bindex((r))
QUS and the bone mineral density (BMD) measured by dual-energy x-ray
absorptiometry at corresponding skeletal sites in young and healthy subjects
(age: 25.0 +/- 3.6 years). Bindex((r))-QUS calculates a density index on the
basis of the thickness of cortical bone measured at the distal radius and the
distal plus proximal tibia. The data show a very good relative and absolute intra
(ICC = 0.977, CV = 1.5%) and inter-session reliability (ICC = 0.978, CV =
1.4%) for the density index. The highest positive correlations were found
between cortical thickness and BMD for the distal radius and distal tibia (r ?
0.71, p < 0.001). The data indicate that the Bindex((r))-QUS parameters are
repeatable within and between measurement sessions. Furthermore, the measurements
reflect the BMD at specific skeletal sites. Bindex((r))-QUS might be a useful
tool for the measurement of skeletal adaptations.
PMID- 27511631
TI - Sweat chloride testing: controversies and issues.
PMID- 27511632
TI - Data security in the brave new world of eHealth.
PMID- 27511630
TI - Inhibition of CDK9 as a therapeutic strategy for inflammatory arthritis.
AB - Rheumatoid arthritis is characterised by synovial inflammation and proliferation
of fibroblast-like synoviocytes. The induction of apoptosis has long been
proposed as a target for proliferative autoimmune diseases, and has further been
shown to act as a successful treatment of experimental models of arthritis, such
as collagen-induced arthritis. Here we examined the effects of specific oral
small-molecule inhibitors of the transcription regulating cyclin-dependent kinase
9 on the development and progression of collagen-induced arthritis. DBA/1 mice
were immunised with bovine collagen type II and treated orally with specific CDK9
inhibitors. The effects of CDK9 inhibition on RNA levels and protein expression,
apoptosis induction, caspase activation and lymphocyte phenotype were further
analysed. Mice showed a significant delay in disease onset and a reduction in
disease severity following treatment with CDK9 inhibitors. Inhibiting CDK9
activity in peripheral blood mononuclear cells resulted in the loss of Mcl-1
expression at both the protein and RNA levels, along with a subsequent increase
in apoptosis. CDK9 specific inhibitors may be a potential alternative treatment
not only of cancer, but also for autoimmune- and inflammatory diseases. Taken
together, these results show that transient inhibition of CDK9 induces apoptosis
in leukocyte subsets and modulates the immune response.
PMID- 27511633
TI - Medicine and Me: a breath of fresh air for IPF.
PMID- 27511634
TI - Corrections.
PMID- 27511635
TI - Amyloid Aggregates Arise from Amino Acid Condensations under Prebiotic
Conditions.
AB - Current theories on the origin of life reveal significant gaps in our
understanding of the mechanisms that allowed simple chemical precursors to
coalesce into the complex polymers that are needed to sustain life. The volcanic
gas carbonyl sulfide (COS) is known to catalyze the condensation of amino acids
under aqueous conditions, but the reported di-, tri-, and tetra-peptides are too
short to support a regular tertiary structure. Here, we demonstrate that alanine
and valine, two of the proteinogenic amino acids believed to have been among the
most abundant on a prebiotic earth, can polymerize into peptides and subsequently
assemble into ordered amyloid fibers comprising a cross-beta-sheet quaternary
structure following COS-activated continuous polymerization of as little as 1 mm
amino acid. Furthermore, this spontaneous assembly is not limited to pure amino
acids, since mixtures of glycine, alanine, aspartate, and valine yield similar
structures.
PMID- 27511637
TI - Parental Self-Control and the Development of Male Aggression in Early Childhood:
A Longitudinal Test of Self-Control Theory.
AB - A number of studies have evaluated associations between parenting practices,
adolescent self-control, and adolescent antisocial behavior. Yet, few studies
have examined associations between these constructs in early childhood or
examined the extent to which both maternal and paternal self-control shapes them.
To address these gaps, the current study utilizes longitudinal data collected on
a sample of 117 Dutch boys and their parents to investigate the across time
interrelationships between parental self-control, ineffective parenting, child
self-control, and child aggression. The results provide evidence of an indirect
association between maternal self-control and early childhood self-control
through maternal ineffective parenting, an indirect association between maternal
ineffective parenting and early childhood aggression through early childhood self
control, and an indirect association between maternal self-control and early
childhood aggression through both maternal ineffective parenting and early
childhood self-control. In contrast, paternal self-control and paternal
ineffective parenting were unrelated to child self-control and child aggression.
The implications and limitations of the study are discussed.
PMID- 27511636
TI - Distribution Characteristics and Combined Effect of Polymorphisms Affecting
Alcohol Consumption Behaviour in the Hungarian General and Roma Populations.
AB - AIMS: Harmful alcohol drinking habits, even among Roma children and adolescents,
are more common than in the majority population. The aim of the study was to
evaluate the genetic susceptibility of Roma to hazardous alcohol consumption
compared to the Hungarian general population. METHODS: A total of 1273 samples
from the population of segregated Hungarian Roma colonies and 2967 samples from
the Hungarian general population were genotyped for 25 polymorphisms. Differences
in genotype and allele distributions were investigated. Genetic risk scores (GRS)
were generated to estimate the joint effect of individual single-nucleotide
polymorphisms (SNPs). After unweighted and weighted GRS were calculated the
distribution of scores in study populations was compared. RESULTS: The allele
frequencies differed significantly between the study populations for 17 SNPs (P <
0.002), but the genetic alterations that predispose to or protect against harmful
alcohol consumption were not overrepresented in the Roma population. The
distribution of unweighted GRS in Roma population was left shifted compared to
general population (P = 0.0013). The median weighted genetic risk score was lower
among the subjects of Roma population compared to the subjects of general
population (0.53 vs 0.65, P = 3.33 * 10-27) even after adjustment for confounding
factors. CONCLUSIONS: Differences in alcohol consumption habits between the
Hungarian Roma and Hungarian general populations do not appear to be linked to
genetic constitution, this behaviour may occur as a result of different cultural
values and environmental exposures. Population-based measures to tackle the
fundamental drivers of consumption, which take account of cultural acceptability,
are needed to reduce harmful alcohol consumption in the Roma population.
PMID- 27511638
TI - Resonant and non-resonant energy transfer from Ce3+ -> X (X = Tb3+ , Eu3+ or
Dy3+ ) in NaMgSO4 F material.
AB - An inorganic NaMgSO4 F fluoride material was prepared by the wet chemical method
and studied for its photoluminescence (PL) and resonant-non-resonant energy
transfer (RET and NORET) capabilities between Ce3+ -> Tb3+ , Ce3+ -> Eu3+ and
Ce3+ -> Dy3+ rare earth ions. The Tb3+ emission for Ce3+ -> Tb3+ transfers
under ultraviolet (UV) wavelengths peaked at 491, 547, and 586 nm, for excitation
at 308 nm due to 5 D4 -> 7 FJ (J = 4, 5, 6) transitions. Eu emission spectra
were observed at 440 nm (Eu2+ ), 593 nm and 616 nm (Eu3+ ) recorded for different
concentrations of materials, whereas Dy3+ emission from Ce3+ -> Dy3+ transfer
under UV wavelengths peaked at 485 nm and 577 nm due to 4 F9/2 -> 6 H15/2 and 6
H13/2 transitions. The purpose of the present study is to understand the RET and
NORET effects of Tb3+ , Eu3+ and Dy3+ co-doping in a NaMgSO4 F:Ce3+ luminescent
material, which could be used as a green-emitting material for lamp phosphors.
PMID- 27511639
TI - Serum levels of 12 renal function and injury markers in patients with
glomerulonephritis.
AB - INTRODUCTION Glomerulonephritis (GN) is a complex disease that affects the
function of the whole nephron. There are few data on the serum levels of the most
common biomarkers of kidney function and injury in GN, or the studies provide
ambiguous results. OBJECTIVES The aim of the study was to evaluate the levels
of known kidney-specific and nonspecific markers of renal function or injury in
the serum of patients with diagnosed primary or secondary GN, with or without the
presence of nephrotic syndrome (NS) and arterial hypertension (AH). PATIENTS AND
METHODS The study included 58 patients with diagnosed GN and 6 patients with
congenital defects (CD) of the kidney and AH (CD+AH). The serum levels of beta2
microglobulin (beta2M), neutrophil-gelatinase associated lipocalin (NGAL),
osteopontin, trefoil factor 3 (TFF-3), calbindin, glutathione-S-transferase- pi
(GST-pi), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and monocyte
chemoattractant protein 1 (MCP-1) were measured with Kidney Toxicity Panels 1 and
2 using the Bio-Plex method. Renalase levels were measured using an enzyme-linked
immunosorbent assay. RESULTS In the whole group and in the subgroups (GN,
GN+AH, GN+NS, CD+AH), NGAL, KIM-1, TFF-3, IL-18, beta2M, and calbindin levels
correlated with estimated glomerular filtration rate (eGFR). In patients with NS,
this correlation for calbindin was reversed. Renalase, MCP-1, GST-pi, and
osteopontin levels were independent of eGFR. Increase in IL-18 levels in the
group with GN was assiociated with lower odds of the kidney disease. When this
group was divided according to eGFR into subgroups G1-G5, TFF-3, NGAL, and beta2M
levels increased with the stage of the disease. CONCLUSIONS In patients with NS,
renalase and MCP-1 might regulate each other's levels. Further studies are needed
to investigate associations between renalase, MCP-1, and osteopontin as factors
unrelated to eGFR in GN. NS may contribute to the loss of calbindin from serum.
NGAL, KIM-1, TFF-3, IL-18, beta2M, and calbindin are good indicators of kidney
function loss in patients with GN.
PMID- 27511640
TI - New insights into the infection of the American cockroach Periplaneta americana
nymphs with Metarhizium anisopliae s.l. (Ascomycota: Hypocreales).
AB - AIMS: To study the marked resistance of Periplaneta americana to entomopathogenic
Metarhizium anisopliae. METHODS AND RESULTS: The low susceptibility of 4th instar
nymphs applied topically with conidia seemed to be related to an active removal
of conidia by the cockroach and to a disabled or retarded germination and
subsequent development of conidia on the cuticle (up to 80% germination in the
next 7 days after application). Inhibitions or delays of germination were related
to the composition of the epicuticular fatty acids (30.1% w/w oleic, 28.3% w/w
linoleic, 24.5% w/w palmitic and 11.7% w/w stearic acid) reported here.
Propagules invading the nymphs through the cuticle took at least 3 days to reach
the haemocoel, and no propagules were found after day 8 post-treatment. Strain IP
46 infected >50% of nymphs treated with doses >=2 * 104 hyphal bodies (HB) nymph
1 and reduced the survival of nymphs <=50%. Most nymphs (>70%) survived after
injection of 6 * 103 and 2 * 103 HB nymph-1 . CONCLUSIONS: Findings emphasize a
distinct resistance of nymphs of the American cockroach to infections by M.
anisopliae. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings provide support
for the development of biological control of this synanthropic cockroach pest.
PMID- 27511641
TI - beta-Secretase (BACE1) inhibitory and neuroprotective effects of p-terphenyls
from Polyozellus multiplex.
AB - Alzheimer's disease (AD), a major neurodegenerative disorder, is associated with
the enzymatic reaction of beta-secretase (BACE1) on the amyloid precursor protein
(APP) for the generation of neurotoxic amyloid-beta (Abeta). Therefore, Abeta
accumulation and oxidative stress-induced neuronal cell death are the pathogenic
hallmarks of AD. In this study, we tried to identify BACE1 inhibitors and
neuroprotectants from natural products, in particular, from the Korean mushroom
Polyozellus multiplex. Four p-terphenyls were identified from the ethanolic
extract of P. multiplex; polyozellin (1), thelephoric acid (2), polyozellic acid
(3), and kynapcin-12 (4). Compounds 1-4 effectively inhibited BACE1 activity with
a half-maximal inhibitory concentration (IC50) of 3.08, 3.50, 4.78, and 15.79
MUM, respectively. Compounds 1-3 reduced the production of neurotoxic Abeta1-42
production in APPswe-N2a cells in a concentration-dependent manner. When HT22
cells were stressed with 5 mM glutamate, compounds 2 and 3 significantly
recovered cell viability. It was correlated with their inhibitory properties
against glutamate-mediated Ca(2+) influx, intracellular reactive oxygen species
(ROS) generation, lipid peroxidation, reduction in Bcl-2 and Bid levels, and
enhanced phosphorylation of mitogen-activated protein kinase (MAPK). Thus, P.
multiplex and the isolated p-terphenyls might be useful in the development of
lead compounds for the prevention of neurodegenerative diseases, especially AD.
PMID- 27511643
TI - Biocompatible Red Fluorescent Organic Nanoparticles with Tunable Size and
Aggregation-Induced Emission for Evaluation of Blood-Brain Barrier Damage.
AB - Detection of damage to the blood-brain barrier (BBB) is important for the
diagnosis of brain diseases and therapeutic drug evaluation. The widely used
probe, Evans blue, suffers from low specificity and high toxicity in vivo. It is
shown that organic nanoparticles with tuneable size, good biocompatibility, and
aggregation-induced emission characteristics offer high detection specificity to
detect BBB damage via a photothrombotic ischemia rat model.
PMID- 27511644
TI - Physiological and pathological clinical conditions and light scattering in brain.
AB - MRI of preterm infants at term commonly reveals subtle brain lesions such as
diffuse white matter injury, which are linked with later cognitive impairments.
The timing and mechanism of such injury remains unclear. The reduced scattering
coefficient of near-infrared light (MUs') has been shown to correlate linearly
with gestational age in neonates. To identify clinical variables associated with
brain MUs', 60 preterm and full-term infants were studied within 7 days of birth.
Dependence of MUs' obtained from the frontal head on clinical variables was
assessed. In the univariate analysis, smaller MUs' was associated with antenatal
glucocorticoid, emergency Caesarean section, requirement for mechanical
ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute
Apgar scores, higher cord blood pH and PO2, and higher blood HCO3(-) at the time
of study. Multivariate analysis revealed that smaller gestational age,
requirement for mechanical ventilation, and higher HCO3(-) at the time of study
were correlated with smaller MUs'. Brain MUs' depended on variables associated
with physiological maturation and pathological conditions of the brain. Further
longitudinal studies may help identify pathological events and clinical
conditions responsible for subtle brain injury and subsequent cognitive
impairments following preterm birth.
PMID- 27511703
TI - Natural product inspired design and synthesis of beta-carboline and gamma-lactone
based molecular hybrids.
AB - beta-Carboline and gamma-lactone moieties have been selected by nature as
privileged scaffolds and display a wide range of pharmacological properties.
Following nature, we envisaged the preparation of new beta-carboline and gamma
lactone based molecular hybrids incorporating both the pharmacophores. In this
regard, a water-assisted In-mediated environmentally benign and easy to execute
single-step tandem Barbier type allylation-lactonisation process has been devised
in order to afford the targeted molecular architectures. It is anticipated that
aqueous medium plays the key role in allylation as well as in the subsequent
lactonisation process for the diastereo-selective synthesis of these conjugates.
It is believed that water drives the reaction pathway through dual activation, it
increases the electrophilic character of formyl and ester functionalities and
simultaneously enhances the nucleophilic potential of the hydroxyl group to
facilitate the in situ intramolecular condensation. Importantly, during this
synthetic strategy no column chromatographic purification was required at any
stage.
PMID- 27511704
TI - Examining the role of socioeconomic deprivation in ethnic differences in sexually
transmitted infection diagnosis rates in England: evidence from surveillance
data.
AB - Differences by ethnic group in STI diagnosis rates have long been recognized in
England. We investigated whether these may be explained by ethnic disparities in
socioeconomic deprivation (SED). Data on all diagnoses made in sexual health
clinics in England in 2013 were obtained from the mandatory STI surveillance
system. Poisson regression was used to calculate incidence rate ratios (IRRs) of
STIs, by ethnicity, with and without adjustment for index of multiple deprivation
(IMD) a measure of area-level deprivation. Unadjusted IRRs (95% confidence
intervals) were highest for gonorrhoea [8.18 (7.77-8.61) and 5.76 (5.28-6.29)]
and genital herpes [4.24 (3.99-4.51) and 3.58 (3.23-3.98)] for people of black
Caribbean and non-Caribbean/non-African black ethnicity and IRRs were highest for
syphilis [8.76 (7.97-9.63)] and genital warts [2.23 (2.17-2.29)] for people of
non-British/non-Irish white ethnicity compared to white British ethnicity. After
adjustment for IMD, IRRs for gonorrhoea [5.76 (5.47-6.07)] and genital herpes
[3.73 (3.50-3.97)] declined but remained highest for black Caribbeans and IRRs
for syphilis [7.35 (6.68-8.09)] and genital warts [2.10 (2.04-2.16)] declined but
remained highest for non-British/non-Irish white compared to white British. In
England, ethnic disparities in STI diagnosis rates are partially explained by
SED, but behavioural and contextual factors likely contribute. Clinic and
community-based interventions should involve social peer networks to ensure they
are targeted and culturally sensitive.
PMID- 27511705
TI - Baseline metabolic disturbances and the twenty-five years risk of incident cancer
in a Mediterranean population.
AB - BACKGROUND AND AIMS: Obesity is predictive of metabolic syndrome (metS), type 2
diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to
assess the risk of incident cancer connected to obesity and metS in a
Mediterranean population characterized by a high prevalence of obesity. METHODS
AND RESULTS: As many as 1133 subjects were enrolled in two phases and followed
for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was
registered in the follow-up period. Anthropometric measures and biochemical
parameters were filed at baseline and evaluated as predictors of incident cancer
by measuring hazards ratios (HR) using multivariate Cox parametric hazards
models. Best predictive threshold for metabolic parameters and metS criteria were
recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0
2.4)] and the TG/HDL ratio (log10) (Males > 0.225, Females > 0.272) [HR = 2.44
(1.3-4.4)] resulted independent predictors of survival free of cancer with a
clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3
4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)].
CONCLUSIONS: Metabolic disturbances are predictive of cancer in a 25 years follow
up of a Mediterranean population following a traditional Mediterranean diet. The
high prevalence of obesity and metS and the observed underlying condition of
insulin resistance expose this population to an increased risk of cardiovascular
disease and cancer despite the healthy nutritional habits.
PMID- 27511706
TI - Comments on "Association of consumption of dairy products and meat with retinal
vessel calibers in subjects at increased cardiovascular risk".
PMID- 27511708
TI - Pilot study on the correlation between skin auto-fluorescence and serum
antioxidant enzyme: skin auto-fluorescence is negatively associated with levels
of malondialdehyde.
AB - BACKGROUND/PURPOSE: Various methods have been used to objectively record skin
changes. However, estimating the intrinsic and extrinsic aging of skin remains a
challenge. Our objective was to study intrinsic skin aging with respect to
patient age and extrinsic photo-aging of human dorsal (photo-exposed) and volar
(photo-protected) forearm in vivo through skin auto-fluorescence (AF). We also
examined the correlations between serum antioxidant enzyme, malondialdehyde(MDA),
and skin AF. METHODS: 37 healthy volunteers were enrolled. We measured skin AF
and its heterogeneity on the dorsal and volar forearms. We also examined serum
concentration of catalase, superoxide dismutase, vitamin E, and MDA levels in
every participant. RESULTS: In photo-protected areas, skin AF intensity in the 40
years or older group was significantly higher compared to the group less than 40
years-old. On the other hand, heterogeneity value was significantly higher in the
less than 40 years-old group in photo-protected area. With respect to serum
antioxidant enzyme and MDA level, only MDA level showed a negative correlation
with skin AF intensity in photo-exposed area. CONCLUSION: We determined that skin
AF intensity of the photo-protected area reflects intrinsic skin aging. In
addition, degree of photo-aging could be indirectly inferred by skin AF of photo
exposed area and serum MDA level.
PMID- 27511707
TI - Synthesis and cardiovascular protective effects of quercetin 7-O-sialic acid.
AB - Oxidative stress and inflammation play important roles in the pathogenesis of
cardiovascular disease (CVD). Oxidative stress-induced desialylation is
considered to be a primary step in atherogenic modification, and therefore, the
attenuation of oxidative stress and/or inflammatory reactions may ameliorate CVD.
In this study, quercetin 7-O-sialic acid (QA) was synthesized aiming to put
together the cardiovascular protective effect of quercetin and the recently
reported anti-oxidant and anti-atherosclerosis functions of N-acetylneuraminic
acid. The biological efficacy of QA was evaluated in vitro in various cellular
models. The results demonstrated that 50 MUM QA could effectively protect human
umbilical vein endothelial cells (HUVEC, EA.hy926) against hydrogen peroxide- or
oxidized low-density lipoprotein-induced oxidative damage by reducing the
production of reactive oxygen species. QA attenuated hydrogen peroxide-induced
desialylation of HUVEC and lipoproteins. QA decreased lipopolysaccharide-induced
secretion of tumour necrosis factor-alpha (TNF-alpha) and monocyte
chemoattractant protein-1 (MCP-1), and it significantly reduced the expression of
intercellular adhesion molecule-1, vascular cell adhesion molecule-1, TNF-alpha
and MCP-1. Furthermore, QA effectively promoted cholesterol efflux from Raw 264.7
macrophages to apolipoprotein A-1 and high-density lipoprotein by up-regulating
ATP-binding cassette transporter A1 and G1, respectively. Results indicated that
the novel compound QA exhibited a better capacity than quercetin for anti
oxidation, anti-inflammation, cholesterol efflux promotion and biomolecule
protection against desialylation and therefore could be a candidate compound for
the prevention or treatment of CVD.
PMID- 27511709
TI - The use of chemometrics to study multifunctional indole alkaloids from Psychotria
nemorosa (Palicourea comb. nov.). Part II: Indication of peaks related to the
inhibition of butyrylcholinesterase and monoamine oxidase-A.
AB - Psychotria nemorosa is chemically characterized by indole alkaloids and displays
significant inhibitory activity on butyrylcholinesterase (BChE) and monoamine
oxidase-A (MAO-A), both enzymes related to neurodegenerative disorders. In the
present study, 43 samples of P. nemorosa leaves were extracted and fractionated
in accordance to previously optimized methods (see Part I). These fractions were
analyzed by means of UPLC-DAD and assayed for their BChE and MAO-A inhibitory
potencies. The chromatographic fingerprint data was first aligned using
correlation optimized warping and Principal Component Analysis to explore the
data structure was performed. Multivariate calibration techniques, namely Partial
Least Squares (PLS1), PLS2 and Orthogonal Projections to Latent Structure (O
PLS1), were evaluated for modelling the activities as a function of the
fingerprints. Since the best results were obtained with O-PLS1 model (RMSECV=9.3
and 3.3 for BChE and MAO-A, respectively), the regression coefficients of the
model were analyzed and plotted relative to the original fingerprints. Four peaks
were indicated as multifunctional compounds, with the capacity to impair both
BChE and MAO-A activities. In order to confirm these results, a semi-prep HPLC
technique was used and a fraction containing the four peaks was purified and
evaluated in vitro. It was observed that the fraction exhibited an IC50 of
2.12MUgmL(-1) for BChE and 1.07MUgmL(-1) for MAO-A. These results reinforce the
prediction obtained by O-PLS1 modelling.
PMID- 27511710
TI - Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral
administration of hydrophilic macromolecular drugs: synthesis, preparation and in
vitro/ex vivo characterization.
AB - Active drug targeting and controlled release of hydrophilic macromolecular drugs
represent crucial points in designing efficient polymeric drug delivery
nanoplatforms. In the present work EGFR-targeted polylactide-co-glycolide (PLGA)
nanoparticles were made by a blend of two different PLGA-based polymers. The
first, GE11-PLGA, in which PLGA was functionalized with GE11, a small peptide and
EGFR allosteric ligand, able to give nanoparticles selective targeting features.
The second polymer was a PEGylated PLGA (PEG-PLGA) aimed at improving
nanoparticles hydrophilicity and stealth features. GE11 and GE11-PLGA were custom
synthetized through a simple and inexpensive method. The nanoprecipitation
technique was exploited for the preparation of polymeric nanoparticles composed
by a 1:1weight ratio between GE11-PLGA and PEG-PLGA, obtaining smart
nanoplatforms with proper size for parenteral administration (143.9+/-5.0nm). In
vitro cellular uptake in EGFR-overexpressing cell line (A549) demonstrated an
active internalization of GE11-functionalized nanoparticles. GE11-PLGA/PEG-PLGA
blend nanoparticles were loaded with Myoglobin, a model hydrophilic
macromolecule, reaching a good loading (2.42% respect to the theoretical 4.00%
w/w) and a prolonged release over 60days. GE11-PLGA/PEG-PLGA blend nanoparticles
showed good in vitro stability for 30days in physiological saline solution at 4
degrees C and for 24h in pH 7.4 or pH 5.0 buffer at 37 degrees C respectively,
giving indications about potential storage and administration conditions.
Furthermore ex vivo stability study in human plasma using fluorescence Single
Particle Tracking (fSPT) assessed good GE11-PLGA/PEG-PLGA nanoparticles
dimensional stability after 1 and 4h. Thanks to the versatility in polymeric
composition and relative tunable nanoparticles features in terms of drug
incorporation and release, GE11-PLGA/PEG-PLGA blend NPs can be considered highly
promising as smart nanoparticulate platforms for the treatment of diseases
characterized by EGFR overexpression by parenteral administration .
PMID- 27511711
TI - Valuable Metals-Recovery Processes, Current Trends, and Recycling Strategies.
AB - This Review provides an overview of valuable metals, the supply of which has been
classified as critical for Europe. Starting with a description of the current
state of the art, novel approaches for their recovery from primary resources are
presented as well as recycling processes. The focus lies on developments since
2005. Chemistry strategies which are used in metal recovery are summarized on the
basis of the individual types of deposit and mineral. In addition, the economic
importance as well as utilization of the metals is outlined.
PMID- 27511712
TI - Application of Cookson-type reagents for biomedical HPLC and LC/MS analyses: a
brief overview.
AB - High-performance liquid chromatography (HPLC), LC/mass spectrometry (MS) and
LC/tandem mass spectrometry (MS/MS) have been widely used for biomedical
analyses, in which chemical derivatization is one of the most important methods
to increase the sensitivity and selectivity. A Cookson-type reagent [4
substituted-1,2,4-triazoline-3,5-dione (4-substituted-TAD)] reacts with the
compound bearing a conjugated diene, such as the vitamin D compound, to
quantitatively form the stable Diels-Alder adduct. The reagent with a chromophore
or fluorophore at the 4-position of TAD yields a highly responsive adduct for the
UV or fluorescence detection, respectively. The Diels-Alder adduct with a Cookson
type reagent having a permanently charged, proton-affinitive or electron
affinitive moiety is sensitively detected by a specific MS analyzer. This paper
is a brief overview of the applications of the reagents for biomedical analyses
mainly using HPLC or LC/MS(/MS).
PMID- 27511713
TI - Evidence of salt accumulation in beach intertidal zone due to evaporation.
AB - In coastal environments, evaporation is an important driver of subsurface
salinity gradients in marsh systems. However, it has not been addressed in the
intertidal zone of sandy beaches. Here, we used field data on an estuarine beach
foreshore with numerical simulations to show that evaporation causes upper
intertidal zone pore-water salinity to be double that of seawater. We found the
increase in pore-water salinity mainly depends on air temperature and relative
humidity, and tide and wave actions dilute a fraction of the high salinity plume,
resulting in a complex process. This is in contrast to previous studies that
consider seawater as the most saline source to a coastal aquifer system, thereby
concluding that seawater infiltration always increases pore-water salinity by
seawater-groundwater mixing dynamics. Our results demonstrate the combined
effects of evaporation and tide and waves on subsurface salinity distribution on
a beach face. We anticipate our quantitative investigation will shed light on the
studies of salt-affected biological activities in the intertidal zone. It also
impacts our understanding of the impact of global warming; in particular, the
increase in temperature does not only shift the saltwater landward, but creates a
different salinity distribution that would have implications on intertidal
biological zonation.
PMID- 27511714
TI - Lymphoedema is a potential sequela of Kaposiform haemangioendothelioma: reply
from the authors.
PMID- 27511715
TI - Stereotactic Radiosurgery for Treatment of Brain Metastases.
AB - Brain metastases are the most common intracranial malignancy. Incidence of brain
metastases has risen as systemic therapies have improved and patients with
metastatic disease live longer. Whole-brain radiation therapy, for many years,
has been the standard treatment approach. Stereotactic radiosurgery has become an
increasingly popular option because of its relatively short, convenient, and
noninvasive treatment course. Although recently published data have renewed
interest in use of whole-brain radiation therapy or systemic therapies for
control of micrometastatic disease, stereotactic radiosurgery continues to be an
important modality, capable of delivering ablative doses of radiation for long
term control of macroscopic disease. The purpose of this review is to explore the
different paradigms for incorporation of stereotactic radiosurgery into
management of brain metastases. Current uses for stereotactic radiosurgery
include delivery as a boost with whole-brain radiation therapy; alone for
patients with a limited number of brain metastases; in pre- or postoperative
settings; and in combination with systemic, targeted, and immune-based therapies.
Mature prospective data on use of stereotactic radiosurgery in combination with
whole-brain radiation therapy is available; however, prospective, randomized data
on stereotactic radiosurgery for patients with a greater number of brain
metastases, its use in pre- and postoperative settings, and its use in
combination with systemic therapies are limited. Data from ongoing and future
studies are needed to define the appropriate use of stereotactic radiosurgery in
these settings.
PMID- 27511716
TI - Searching for Synergy: Combining Drugs and Stereotactic Radiosurgery for the
Treatment of Brain Metastases.
PMID- 27511717
TI - Stereotactic Radiosurgery for Brain Metastases: More Work to Be Done.
PMID- 27511718
TI - Multidisciplinary Care of Laryngeal Cancer.
AB - Treatment of larynx cancer has changed dramatically over the past several years.
Novel modalities of treatment have been introduced as organ preservation has been
developed. In addition, new targeted therapies have appeared, and improvements in
radiotherapeutic and surgical techniques have been introduced. Thus, a large
variety of treatment options is increasing local control rates and overall
survival; however, selecting the most appropriate treatment remains a challenging
decision. This article focuses on the multidisciplinary care of early-stage and
locally advanced larynx cancer and attempts to sum up different approaches.
Moreover, it reviews state-of-the-art treatment in larynx preservation, which has
been consolidated in recent years.
PMID- 27511719
TI - A Multidisciplinary Approach to Larynx Cancer: One Size Does Not Fit All.
PMID- 27511720
TI - Functional Organ Preservation in Larynx Cancer: A Continuing Debate.
PMID- 27511721
TI - Acute, Unilateral Breast Toxicity From Gemcitabine in the Setting of Thoracic
Inlet Obstruction.
PMID- 27511722
TI - Environmental change makes robust ecological networks fragile.
AB - Complex ecological networks appear robust to primary extinctions, possibly due to
consumers' tendency to specialize on dependable (available and persistent)
resources. However, modifications to the conditions under which the network has
evolved might alter resource dependability. Here, we ask whether adaptation to
historical conditions can increase community robustness, and whether such
robustness can protect communities from collapse when conditions change. Using
artificial life simulations, we first evolved digital consumer-resource networks
that we subsequently subjected to rapid environmental change. We then
investigated how empirical host-parasite networks would respond to historical,
random and expected extinction sequences. In both the cases, networks were far
more robust to historical conditions than new ones, suggesting that new
environmental challenges, as expected under global change, might collapse
otherwise robust natural ecosystems.
PMID- 27511723
TI - Identification of microRNA profiles associated with refractory primary biliary
cirrhosis.
AB - MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that control the target
gene translation by RNA interference; miRNAs are associated with cellular
processes, including proliferation, differentiation, apoptosis, and cell
survival. Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease
of unknown etiology. One third of patients with PBC demonstrate suboptimal
responses, which result in worse outcomes. It has been previously reported that
miRNAs are involved in drug resistance, however, the association between miRNA
expression levels and refractory PBC remains to be fully elucidated. In the
present study, among the 20 patients with PBC treated with ursodeoxycholic acid
or bezafibrate, 15 patients were classed as treatment-effective, and 5 were
classed as being treatment-resistant. Using the miRNA array technique, miRNA
profiles were identified for each group. A total of 35 miRNAs were significantly
upregulated, and 23 were significantly downregulated in the treatment-resistant
group compared with the treatment-effective group. In order to examine the
association between the highly altered miRNAs and clinical features of the two
groups, numerous parameters were analyzed. Elevated levels of direct bilirubin,
aspartate transaminase (AST), and alanine transaminase (ALT) were identified to
be associated with miRNA-122 upregulation. AST, ALT, and gamma guanosine
triphosphate were additionally associated with miRNA-378f upregulation. However,
the reduction of miRNA-4311 was associated with reduced levels of AST and ALT.
miRNA-4714-3p was also negatively correlated with total bilirubin and lactate
dehydrogenase. Therefore, identifying the miRNA profile was demonstrated to be a
useful approach in the characterization of PBC development. It is suggested that
highly altered miRNAs may be potential biomarkers for use in the development of
treatment of patients with refractory PBC.
PMID- 27511724
TI - A novel missense mutation of the GRK1 gene in Oguchi disease.
AB - Oguchi disease is a rare form of congenital stationary night blindness with an
autosomal recessive inheritance pattern. The presence of S-antigen (SAG) and G
protein-dependent receptor kinase 1 (GRK1) mutations were investigated in the
family members with Oguchi disease. All exons of the SAG and GRK1 genes were
amplified by polymerase chain reaction and sequenced. The patients were shown to
have characteristic clinical features of Oguchi disease. Gene analysis determined
a novel GRK1 mutation c.923T>C, which caused Oguchi disease in all siblings. This
mutation, was demonstrated by amino acid alignment analysis to be in a
phylogenetically conserved region and resulted in an amino acid change from
leucine to proline at position 308. Thus, the present study reports a novel
missense mutation of GRK1 in the affected members of a consanguineous Turkish
family. Homozygosity at position 308, which resides in the catalytic domain of
the GRK1 gene, is the cause of Oguchi disease in this Turkish family.
PMID- 27511725
TI - Gene set analysis for interpreting genetic studies.
AB - Interpretation of genome-wide association study (GWAS) results is lacking behind
the discovery of new genetic associations. Consequently, there is an urgent need
for data-driven methods for interpreting genetic association studies. Gene set
analysis (GSA) can identify aetiologic pathways and functional annotations and
may hence point towards novel biological insights. However, despite the growing
availability of GSA tools, the sizeable amount of variants identified for a vast
number of complex traits, and many irrefutably trait-associated gene sets, the
gap between discovery and interpretation remains. More efficient interpretation
requires more complete and consistent gene set representations of biological
pathways, phenotypes and functional annotations. In this review, I examine
different types of gene sets, discuss how inconsistencies in gene set definitions
impact GSA, describe how GSA has helped to elucidate biology and outline
potential future directions.
PMID- 27511726
TI - HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies of 10 918 Koreans from
bone marrow donor registry in Korea.
AB - The human leucocyte antigen (HLA) system is the most polymorphic genetic system
in humans, and HLA matching is crucial in organ transplantation, especially in
hematopoietic stem cell transplantation. We investigated HLA-A, HLA-B and HLA
DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from
bone marrow donor registry in Korea. Intermediate resolution HLA typing was
performed using Luminex technology (Wakunaga, Japan), and additional allelic
level typing was performed using PCR-single-strand conformation polymorphism
method and/or sequence-based typing (Abbott Molecular, USA). Allele and haplotype
frequencies were calculated by direct counting and maximum likelihood methods,
respectively. A total of 39 HLA-A, 66 HLA-B and 47 HLA-DRB1 alleles were
identified. High-frequency alleles found at a frequency of >=5% were 6 HLA-A
(A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA-B (B*15:01, *35:01,
*44:03, *51:01, 54:01 and *58:01) and 8 HLA-DRB1 (DRB1*01:01, *04:05, *04:06,
*07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and
DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12
and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA
A-B-DRB1 haplotypes were estimated with frequencies of >=0.05%, >=0.1% and
>=0.5%, respectively. The five most common haplotypes with frequencies of >=2.0%
were A*33:03-B*44:03-DRB1*13:02 (4.97%), A*33:03-B*58:01-DRB1*13:02, A*33:03
B*44:03-DRB1*07:01, A*24:02-B*07:02-DRB1*01:01 and A*24:02-B*52:01-DRB1*15:02.
Among 34 serologic HLA-A-B-DR haplotypes with frequencies of >=0.5%, 17
haplotypes revealed allele-level diversity and majority of the allelic variation
was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype
diversity obtained in this study is the most comprehensive data thus far reported
in Koreans, and the information will be useful for unrelated stem cell
transplantation as well as for disease association studies.
PMID- 27511727
TI - Knowledge of and Preparedness for Use of Environmental Assessments in Shelters
During Disasters: Results of the 2013 State and Territorial Use of Shelter
Assessments Survey.
AB - OBJECTIVE: Environmental health assessments of disaster shelters are critical for
monitoring the living conditions of the occupants. However, knowledge and levels
of utilization of these assessments have never been estimated in the United
States or its territories. We aimed to conduct a cross-sectional survey to
ascertain knowledge and Utilization of environmental health disaster shelter
assessments. METHODS: The State and Territorial Use of Shelter Assessments Survey
(STUSA) of environmental health department directors (N=56) was carried out in
2013. RESULTS: Survey responses were received from 55 of 56 targeted
jurisdictions. Of those respondents, 92% of state jurisdictions and 100% of
territories reported having knowledge about shelter assessments. However, only
40% of states and 60% of territories reported receiving formal training, and 53%
of states and 50% of territories reported having operational procedures for
shelter assessments. High levels of knowledge and familiarity and low levels of
training and processes for operationalizing assessments were assessed.
CONCLUSIONS: Because environmental health assessments may provide useful
information in disaster settings, we need to understand the barriers to their
implementation. The results of these assessments may also help to validate their
usefulness in protecting shelter occupants during disasters. (Disaster Med Public
Health Preparedness. 2017;11:11-14).
PMID- 27511729
TI - Unsupervised HLA Peptidome Deconvolution Improves Ligand Prediction Accuracy and
Predicts Cooperative Effects in Peptide-HLA Interactions.
AB - Ag presentation on HLA molecules plays a central role in infectious diseases and
tumor immunology. To date, large-scale identification of (neo-)Ags from DNA
sequencing data has mainly relied on predictions. In parallel, mass spectrometry
analysis of HLA peptidome is increasingly performed to directly detect peptides
presented on HLA molecules. In this study, we use a novel unsupervised approach
to assign mass spectrometry-based HLA peptidomics data to their cognate HLA
molecules. We show that incorporation of deconvoluted HLA peptidomics data in
ligand prediction algorithms can improve their accuracy for HLA alleles with few
ligands in existing databases. The results of our computational analysis of large
datasets of naturally processed HLA peptides, together with experimental
validation and protein structure analysis, further reveal how HLA-binding motifs
change with peptide length and predict new cooperative effects between distant
residues in HLA-B07:02 ligands.
PMID- 27511728
TI - Suppression of Glut1 and Glucose Metabolism by Decreased Akt/mTORC1 Signaling
Drives T Cell Impairment in B Cell Leukemia.
AB - Leukemia can promote T cell dysfunction and exhaustion that contributes to
increased susceptibility to infection and mortality. The treatment-independent
mechanisms that mediate leukemia-associated T cell impairments are poorly
understood, but metabolism tightly regulates T cell function and may contribute.
In this study, we show that B cell leukemia causes T cells to become activated
and hyporesponsive with increased PD-1 and TIM3 expression similar to exhausted T
cells and that T cells from leukemic hosts become metabolically impaired.
Metabolic defects included reduced Akt/mammalian target of rapamycin complex 1
(mTORC1) signaling, decreased expression of the glucose transporter Glut1 and
hexokinase 2, and reduced glucose uptake. These metabolic changes correlated with
increased regulatory T cell frequency and expression of PD-L1 and Gal-9 on both
leukemic and stromal cells in the leukemic microenvironment. PD-1, however, was
not sufficient to drive T cell impairment, as in vivo and in vitro anti-PD-1
blockade on its own only modestly improved T cell function. Importantly, impaired
T cell metabolism directly contributed to dysfunction, as a rescue of T cell
metabolism by genetically increasing Akt/mTORC1 signaling or expression of Glut1
partially restored T cell function. Enforced Akt/mTORC1 signaling also decreased
expression of inhibitory receptors TIM3 and PD-1, as well as partially improved
antileukemia immunity. Similar findings were obtained in T cells from patients
with acute or chronic B cell leukemia, which were also metabolically exhausted
and had defective Akt/mTORC1 signaling, reduced expression of Glut1 and
hexokinase 2, and decreased glucose metabolism. Thus, B cell leukemia-induced
inhibition of T cell Akt/mTORC1 signaling and glucose metabolism drives T cell
dysfunction.
PMID- 27511730
TI - Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity.
AB - Defects of the intracellular enzyme 3' repair exonuclease 1 (Trex1) cause the
rare autoimmune condition Aicardi-Goutieres syndrome and are associated with
systemic lupus erythematosus. Trex1(-/-) mice develop type I IFN-driven
autoimmunity, resulting from activation of the cytoplasmic DNA sensor cyclic GMP
AMP synthase by a nucleic acid substrate of Trex1 that remains unknown. To
identify cell types responsible for initiation of autoimmunity, we generated
conditional Trex1 knockout mice. Loss of Trex1 in dendritic cells was sufficient
to cause IFN release and autoimmunity, whereas Trex1-deficient keratinocytes and
microglia produced IFN but did not induce inflammation. In contrast, B cells,
cardiomyocytes, neurons, and astrocytes did not show any detectable response to
the inactivation of Trex1. Thus, individual cell types differentially respond to
the loss of Trex1, and Trex1 expression in dendritic cells is essential to
prevent breakdown of self-tolerance ensuing from aberrant detection of endogenous
DNA.
PMID- 27511731
TI - A Histone Methyltransferase ESET Is Critical for T Cell Development.
AB - ESET/SETDB1, one of the major histone methyltransferases, catalyzes histone 3
lysine 9 (H3K9) trimethylation. ESET is critical for suppressing expression of
retroviral elements in embryonic stem cells; however, its role in the immune
system is not known. We found that thymocyte-specific deletion of ESET caused
impaired T cell development, with CD8 lineage cells being most severely affected.
Increased apoptosis of CD8 single-positive cells was observed, and TCR-induced
ERK activation was severely inhibited in ESET(-/-) thymocytes. Genome-wide
comprehensive analysis of mRNA expression and H3K9 trimethylation revealed that
ESET regulates expression of numerous genes in thymocytes. Among them,
FcgammaRIIB, whose signaling can inhibit ERK activation, was strongly and
ectopically expressed in ESET(-/-) thymocytes. Indeed, genetic depletion of
FcgammaRIIB in ESET(-/-) thymocytes rescued impaired ERK activation and partially
restored defective positive selection in ESET(-/-) mice. Therefore, impaired T
cell development in ESET(-/-) mice is partly due to the aberrant expression of
FcgammaRIIB. Collectively, to our knowledge, we identify ESET as the first
trimethylated H3K9 histone methyltransferase playing a crucial role in T cell
development.
PMID- 27511732
TI - Diversified Anchoring Features the Peptide Presentation of DLA-88*50801: First
Structural Insight into Domestic Dog MHC Class I.
AB - Canines represent a crucial animal model for studying human diseases and organ
transplantation, as well as the evolution of domestic animals. MHCs, with a
central role in cellular immunity, are commonly used in the study of dog
population genetics and genome evolution. However, the molecular basis for the
peptide presentation of dog MHC remains largely unknown. In this study, peptide
presentation by canine MHC class I DLA-88*50801 was structurally determined,
revealing diversified anchoring modes of the binding peptides. Flexible and large
pockets composed of both hydrophobic and hydrophilic residues can accommodate
pathogen-derived peptides with diverse anchor residues, as confirmed by
thermostability measurements. Furthermore, DLA-88*50801 contains an unusual
alpha2 helix with a large coil in the TCR contact region. These results further
our understanding of canine T cell immunity through peptide presentation of MHC
class I and shed light on the molecular basis for vaccine development for canine
infectious diseases, for example, canine distemper virus.
PMID- 27511733
TI - Systems Analysis of the Complement-Induced Priming Phase of Liver Regeneration.
AB - Liver regeneration is a well-orchestrated process in the liver that allows mature
hepatocytes to reenter the cell cycle to proliferate and replace lost or damaged
cells. This process is often impaired in fatty or diseased livers, leading to
cirrhosis and other deleterious phenotypes. Prior research has established the
role of the complement system and its effector proteins in the progression of
liver regeneration; however, a detailed mechanistic understanding of the
involvement of complement in regeneration is yet to be established. In this
study, we have examined the role of the complement system during the priming
phase of liver regeneration through a systems level analysis using a combination
of transcriptomic and metabolomic measurements. More specifically, we have
performed partial hepatectomy on mice with genetic deficiency in C3, the major
component of the complement cascade, and collected their livers at various time
points. Based on our analysis, we show that the C3 cascade activates c-fos and
promotes the TNF-alpha signaling pathway, which then activates acute-phase genes
such as serum amyloid proteins and orosomucoids. The complement activation also
regulates the efflux and the metabolism of cholesterol, an important metabolite
for cell cycle and proliferation. Based on our systems level analysis, we provide
an integrated model for the complement-induced priming phase of liver
regeneration.
PMID- 27511734
TI - Regulatory T Cell Numbers in Inflamed Skin Are Controlled by Local Inflammatory
Cues That Upregulate CD25 and Facilitate Antigen-Driven Local Proliferation.
AB - CD4(+)Foxp3(+) regulatory T cells (Tregs) are key immune suppressors that
regulate immunity in diverse tissues. The tissue and/or inflammatory signals that
influence the magnitude of the Treg response remain unclear. To define signals
that promote Treg accumulation, we developed a simple system of skin inflammation
using defined Ags and adjuvants that induce distinct cytokine milieus: OVA
protein in CFA, aluminum salts (Alum), and Schistosoma mansoni eggs (Sm Egg).
Polyclonal and Ag-specific Treg accumulation in the skin differed significantly
between adjuvants. CFA and Alum led to robust Treg accumulation, with >50% of all
skin CD4(+) T cells being Foxp3(+) In contrast, Tregs accumulated poorly in the
Sm Egg-inflamed skin. Surprisingly, we found no evidence of inflammation-specific
changes to the Treg gene program between adjuvant-inflamed skin types, suggesting
a lack of selective recruitment or adaptation to the inflammatory milieu.
Instead, Treg accumulation patterns were linked to differences in CD80/CD86
expression by APC and the regulation of CD25 expression, specifically in the
inflamed skin. Inflammatory cues alone, without cognate Ag, differentially
supported CD25 upregulation (CFA and Alum > Sm Egg). Only in inflammatory milieus
that upregulated CD25 did the provision of Ag enhance local Treg proliferation.
Reduced IL-33 in the Sm Egg-inflamed environment was shown to contribute to the
failure to upregulate CD25. Thus, the magnitude of the Treg response in inflamed
tissues is controlled at two interdependent levels: inflammatory signals that
support the upregulation of the important Treg survival factor CD25 and Ag
signals that drive local expansion.
PMID- 27511735
TI - Expansion and Protection by a Virus-Specific NK Cell Subset Lacking Expression of
the Inhibitory NKR-P1B Receptor during Murine Cytomegalovirus Infection.
AB - NK cells play a major role in immune defense against human and murine CMV (MCMV)
infection. Although the MCMV genome encodes for MHC class I-homologous decoy
ligands for inhibitory NK cell receptors to evade detection, some mouse strains
have evolved activating receptors, such as Ly49H, to recognize these ligands and
initiate an immune response. In this study, we demonstrate that approximately
half of the Ly49H-expressing (Ly49H(+)) NK cells in the spleen and liver of
C57BL/6 mice also express the inhibitory NKR-P1B receptor. During MCMV infection,
the NKR-P1B(-)Ly49H(+) NK cell subset proliferates to constitute the bulk of the
NK cell population. This NK cell subset also confers better protection against
MCMV infection compared with the NKR-P1B(+)Ly49H(+) subset. The two populations
are composed of cells that differ in their surface expression of receptors such
as Ly49C/I and NKG2A/C/E, as well as developmental markers, CD27 and CD11b, and
the high-affinity IL-2R (CD25) following infection. Although the NKR-P1B(+) NK
cells can produce effector molecules such as IFNs and granzymes, their
proliferation is inhibited during infection. A similar phenotype in MCMV-infected
Clr-b-deficient mice, which lack the ligand for NKR-P1B, suggests the involvement
of ligands other than the host Clr-b. Most interestingly, genetic deficiency of
the NKR-P1B, but not Clr-b, results in accelerated virus clearance and recovery
from MCMV infection. This study is particularly significant because the mouse NKR
P1B:Clr-b receptor:ligand system represents the closest homolog of the human NKR
P1A:LLT1 system and may have a direct relevance to human CMV infection.
PMID- 27511737
TI - Transient Expression of Transgenic IL-12 in Mouse Liver Triggers Unremitting
Inflammation Mimicking Human Autoimmune Hepatitis.
AB - The etiopathogenesis of autoimmune hepatitis (AIH) remains poorly understood. In
this study, we sought to develop an animal model of human AIH to gain insight
into the immunological mechanisms driving this condition. C57BL/6 mice were i.v.
injected with adeno-associated viral vectors encoding murine IL-12 or luciferase
under the control of a liver-specific promoter. Organ histology, response to
immunosuppressive therapy, and biochemical and immunological parameters,
including Ag-specific humoral and cellular response, were analyzed. Mechanistic
studies were carried out using genetically modified mice and depletion of
lymphocyte subpopulations. Adeno-associated virus IL-12-treated mice developed
histological, biochemical, and immunological changes resembling type 1 AIH,
including marked and persistent liver mononuclear cell infiltration, hepatic
fibrosis, hypergammaglobulinemia, anti-nuclear and anti-smooth muscle actin Abs,
and disease remission with immunosuppressive drugs. Interestingly, transgenic IL
12 was short-lived, but endogenous IL-12 expression was induced, and both IL-12
and IFN-gamma remained elevated during the entire study period. IFN-gamma was
identified as an essential mediator of liver damage, and CD4 and CD8 T cells but
not NK, NKT, or B cells were essential executors of hepatic injury. Furthermore,
both MHC class I and MHC class II expression was upregulated at the
hepatocellular membrane, and induction of autoreactive liver-specific T cells was
detected. Remarkably, although immunoregulatory mechanisms were activated, they
only partially mitigated liver damage. Thus, low and transient expression of
transgenic IL-12 in hepatocytes causes loss of tolerance to hepatocellular Ags,
leading to chronic hepatitis resembling human AIH type 1. This model provides a
practical tool to explore AIH pathogenesis and novel therapies.
PMID- 27511736
TI - Herpesvirus-Associated Lymphadenitis Distorts Fibroblastic Reticular Cell
Microarchitecture and Attenuates CD8 T Cell Responses to Neurotropic Infection in
Mice Lacking the STING-IFNalpha/beta Defense Pathways.
AB - Type I IFN (IFN-alpha/beta)-driven immune responses to acute viral infection are
critical to counter replication and prevent dissemination. However, the
mechanisms underlying host resistance to HSV type 1 (HSV-1) are incompletely
understood. In this study, we show that mice with deficiencies in IFN-alpha/beta
signaling or stimulator of IFN genes (STING) exhibit exacerbated neurovirulence
and atypical lymphotropic dissemination of HSV-1 following ocular infection.
Synergy between IFN-alpha/beta signaling and efficacy of early adaptive immune
responses to HSV-1 were dissected using bone marrow chimeras and adoptive cell
transfer approaches to profile clonal expansion, effector function, and
recruitment of HSV-specific CD8(+) T cells. Lymphotropic viral dissemination was
commensurate with abrogated CD8(+) T cell responses and pathological alterations
of fibroblastic reticular cell networks in the draining lymph nodes. Our results
show that resistance to HSV-1 in the trigeminal ganglia during acute infection is
conferred in part by STING and IFN-alpha/beta signaling in both bone marrow
derived and -resident cells, which coalesce to support a robust HSV-1-specific
CD8(+) T cell response.
PMID- 27511740
TI - SolCos model-based individual reminiscence for older adults with mild to moderate
dementia in nursing homes: a randomized controlled intervention study.
AB - : WHAT IS KNOWN ON THE SUBJECT?: To stimulate reminiscence of older adults with
dementia performed individually or through group sessions is a well-known
practice in nursing homes resulting in effects on behaviour and well-being as an
alternative for medication. Robust scientific proof of the effectiveness of
individual reminiscence therapy performed in nursing homes is sparse. WHAT THIS
PAPER ADDS TO EXISTING KNOWLEDGE?: We have provided individual standardized
reminiscence therapy to residents with dementia. The therapy was developed and
tested in a previous study and performed in this study by trained nursing home
volunteers. In comparison with a control group who received usual care, residents
who received the reminiscence therapy showed significant less depressive
symptoms. Moreover, residents were, in general, attentive, open and collaborative
during the sessions and volunteers experienced the sessions as useful and
pleasant. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Individual reminiscence
therapy can be learned and used by nursing home volunteers to improve care in
nursing homes. ABSTRACT: Aim To investigate the effect of a standardized
individualized intervention based on the SolCos transformational reminiscence
model on depressive symptoms (primary outcome), cognition and behaviour
(secondary outcomes) for older people with mild to moderate dementia, performed
by trained nursing home volunteers as facilitators. Background Because of limited
pharmacological treatment options for older adults with dementia relevant
physical, sensory, psychological or social interventions offer alternative
opportunities. Method Randomized controlled trial (ISRCTN74355073) was set up in
two nursing homes with 29 and 31 residents in the intervention and the control
groups respectively. Eighteen nursing home volunteers were trained to perform the
reminiscence therapy. Various assessment scales were measured pre- and post
sessions. Results Linear regression analysis showed an impact on depressive
symptoms. However, no impact was identified on cognition and behaviour.
Facilitators experienced the sessions as useful and pleasant, and study
participants were, in general, attentive, open and collaborative. Discussion
Study results showed that organizing standardized individual reminiscence therapy
with nursing home volunteers was feasible and study participants' attention and
participation were overall good. Further study initiatives to explore the
potential of individual reminiscence therapy within a person-centred framework
are recommended in order to improve care in nursing homes.
PMID- 27511738
TI - Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome.
AB - Antisynthetase syndrome (aSS) is characterized by the association of interstitial
lung disease and myositis with anti-tRNA synthetase autoantibodies. Immune
mechanisms leading to aSS could be initiated in the lungs, but the role of NK
cells has not yet been studied. Both extensive NK cell phenotype and functions
were compared between 33 patients and 26 controls. Direct and redirected
polyfunctionality assays (degranulation and intracellular production of TNF-alpha
and IFN-gamma) were performed spontaneously or after IL-12 plus IL-18 stimulation
in the presence of K562 or P815 target cells, respectively. NK cells from
inactive patients showed normal phenotype, whereas active aSS revealed a
differentiated NK cell profile, as indicated by increased CD57 and Ig-like
transcript 2 and an inability to produce IFN-gamma (p = 0.002) compared with
controls. Importantly, active aSS was more specifically associated with a
significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular
protein were similar in aSS and healthy controls. This NKp30 decrease was
strongly correlated with reduced NK cell polyfunctionality in both direct and
redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03,
respectively), confirming its important impact in aSS. Histological studies
revealed massive infiltrations of NK cells inside the lungs of aSS patients (148
versus 11/mm(2)). Taken together, these data suggest that NK cells and NKp30
could play a role in aSS pathogenesis.
PMID- 27511739
TI - Characterization of the Filum terminale as a neural progenitor cell niche in both
rats and humans.
AB - Neural stem cells (NSCs) reside in a unique microenvironment within the central
nervous system (CNS) called the NSC niche. Although they are relatively rare,
niches have been previously characterized in both the brain and spinal cord of
adult animals. Recently, another potential NSC niche has been identified in the
filum terminale (FT), which is a thin band of tissue at the caudal end of the
spinal cord. While previous studies have demonstrated that NSCs can be isolated
from the FT, the in vivo architecture of this tissue and its relation to other
NSC niches in the CNS has not yet been established. In this article we report a
histological analysis of the FT NSC niche in postnatal rats and humans.
Immunohistochemical characterization reveals that the FT is mitotically active
and its cells express similar markers to those in other CNS niches. In addition,
the organization of the FT most closely resembles that of the adult spinal cord
niche. J. Comp. Neurol. 525:661-675, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27511741
TI - Ungual aspergillosis successfully treated with topical efinaconazole.
PMID- 27511742
TI - A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the
treatment of cardiovascular risk factors of metabolic syndrome.
AB - This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the
treatment of hyperglycaemia and other cardiovascular risk components of metabolic
syndrome using a prospective, double-blind, randomised, placebo-controlled trial.
Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome
were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma
lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma
lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome
measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma
glucose [FPG]); a number of secondary outcome measures were also tested. Data
from the two intervention groups were combined. The combined intervention had no
effect on any of the primary (baseline-adjusted difference in means: HbA1c =
0.13%, 95% CI [-0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [-0.90, 0.96], p
= 0.95) or secondary outcome measures over the course of the 16-week trial, and
no overall increased risk of adverse events with either active treatment.
Evidence from this randomised clinical trial does not support the use of
Ganoderma lucidum for treatment of cardiovascular risk factors in people with
diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with
the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial
ID: ACTRN12606000485538 and can be accessed here:
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705.
PMID- 27511743
TI - VHLdb: A database of von Hippel-Lindau protein interactors and mutations.
AB - Mutations in von Hippel-Lindau tumor suppressor protein (pVHL) predispose to
develop tumors affecting specific target organs, such as the retina, epididymis,
adrenal glands, pancreas and kidneys. Currently, more than 400 pVHL interacting
proteins are either described in the literature or predicted in public databases.
This data is scattered among several different sources, slowing down the
comprehension of pVHL's biological role. Here we present VHLdb, a novel database
collecting available interaction and mutation data on pVHL to provide novel
integrated annotations. In VHLdb, pVHL interactors are organized according to two
annotation levels, manual and automatic. Mutation data are easily accessible and
a novel visualization tool has been implemented. A user-friendly feedback
function to improve database content through community-driven curation is also
provided. VHLdb presently contains 478 interactors, of which 117 have been
manually curated, and 1,074 mutations. This makes it the largest available
database for pVHL-related information. VHLdb is available from URL:
http://vhldb.bio.unipd.it/.
PMID- 27511744
TI - Recursive partition analysis of peritoneal and systemic recurrence in patients
with gastric cancer who underwent D2 gastrectomy: Implications for neoadjuvant
therapy consideration.
AB - BACKGROUND AND OBJECTIVES: To classify patients with nonmetastatic advanced
gastric cancer who underwent D2-gastrectomy into prognostic groups based on
peritoneal and systemic recurrence risks. METHODS: Between 2004 and 2007, 1,090
patients with T3-4 or N+ gastric cancer were identified from our registry.
Recurrence rates were estimated using a competing-risk analysis. Different
prognostic groups were defined using recursive partitioning analysis (RPA).
RESULTS: Median follow-up was 7 years. In the RPA-model for peritoneal recurrence
risk, the initial node was split by T stage, indicating that differences between
patients with T1-3 and T4 cancer were the greatest. The 5-year peritoneal
recurrence rates for patients with T4 (n = 627) and T1-3 (n = 463) disease were
34.3% and 9.1%, respectively. N stage and neural invasion had an additive impact
on high-risk patients. The RPA model for systemic relapse incorporated N stage
alone and gave two terminal nodes: N0-2 (n = 721) and N3 (n = 369). The 5-year
cumulative incidences were 7.7% and 24.5%, respectively. CONCLUSIONS: We proposed
risk stratification models of peritoneal and systemic recurrence in patients
undergoing D2-gastrectomy. This classification could be used for stratification
protocols in future studies evaluating adjuvant therapies such as preoperative
chemoradiotherapy. J. Surg. Oncol. 2016;114:859-864. (c) 2016 2016 Wiley
Periodicals, Inc.
PMID- 27511745
TI - Birth defects and neonatal morbidity caused by teratogen exposure after the
embryonic period.
AB - BACKGROUND: Pharmaceutical pregnancy exposure registries seek to evaluate
temporal associations between drug exposures and adverse outcomes, particularly
congenital anomalies. These registries record observed associations that may or
may not be causally-related to the exposure. Most major congenital malformations
(i.e., structural birth defects) result from abnormal development during
embryogenesis. A standardized catalog of defects of concern (colloquially the
"BPA Codes") is used both in public health surveillance programs and pregnancy
exposure registries. There are, however, some anomalies that cause significant
morbidity and mortality for which isolated second or third trimester exposures
may be pathogenically significant. There currently exists no standardized list of
defects for which exposure limited to the fetal period may be problematic.
METHODS: The six-digit-code list was used to determine anomalies that might
result from medication exposures limited to the fetal period. RESULTS: Defects
with documented first trimester pathogenesis (e.g., anencephaly, heterotaxy) were
eliminated from consideration, as were chromosomal and single gene disorders
(e.g., trisomy 21, achondroplasia). The remaining defects include the following:
(1) those that are known to or could reasonably originate or manifest after the
embryonic period (e.g., porencephaly, cataracts); (2) those for which
pathogenesis is unclear or variable enough that exposure at any gestational age
might be considered relevant (e.g., club foot, microcephaly); and (3) those that
include some component of abnormal growth (e.g., hemihyperplasia). "Unspecified"
defects (e.g., "abnormality of the leg") were included by default because there
is insufficient information to assume first trimester embryogenesis. CONCLUSION:
The final result is a list of major and minor anomalies in 11 organ system
categories that may be caused by teratogen exposure during the fetal period.
Birth Defects Research (Part A) 106:935-939, 2016. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27511746
TI - Social exclusion modulates priorities of attention allocation in cognitive
control.
AB - Many studies have investigated how exclusion affects cognitive control and have
reported inconsistent results. However, these studies usually treated cognitive
control as a unitary concept, whereas it actually involved two main sub
processes: conflict detection and response implementation. Furthermore, existing
studies have focused primarily on exclusion's effects on conscious cognitive
control, while recent studies have shown the existence of unconscious cognitive
control. Therefore, the present study investigated whether and how exclusion
affects the sub-processes underlying conscious and unconscious cognitive control
differently. The Cyberball game was used to manipulate social exclusion and
participants subsequently performed a masked Go/No-Go task during which event
related potentials were measured. For conscious cognitive control, excluded
participants showed a larger N2 but smaller P3 effects than included
participants, suggesting that excluded people invest more attention in conscious
conflict detection, but less in conscious inhibition of impulsive responses.
However, for unconscious cognitive control, excluded participants showed a
smaller N2 but larger P3 effects than included participants, suggesting that
excluded people invest less attention in unconscious conflict detection, but more
in unconscious inhibition of impulsive responses. Together, these results suggest
that exclusion causes people to rebalance attention allocation priorities for
cognitive control according to a more flexible and adaptive strategy.
PMID- 27511747
TI - Analysis of protein profiling studies of beta-thalassemia/Hb E disease.
AB - A number of studies have used global protein profiling technologies on a range of
patient samples to detect proteins that are differentially expressed in beta
thalassemia/Hb E as an aid for understanding the physiopathology of this disease.
Seven studies have identified a total of 111 unique, differentially expressed
proteins. Seven proteins (prothrombin, alpha-1-antichymotrypsin, fibrinogen beta
chain, hemoglobin beta, selenium-binding protein, microtubule-actin cross-linking
factor and adenomatous polyposis coli protein 2) have been identified in two
independent studies, whereas two proteins (carbonic anhydrase 1 and peroxiredoxin
2) have been identified in three independent studies. Both of these latter two
proteins were consistently upregulated in the studies that identified them.
Ontological analysis of all differentially regulated proteins identified
"response to inorganic substances" as the most significant functional annotation
cluster, which is consistent with iron overload being a major pathological
consequence of this disease. Despite the range of samples investigated and the
relatively small number of studies undertaken, a coherent picture of the
mediators of the pathological consequences of beta-thalassemia/Hb E disease is
starting to emerge.
PMID- 27511748
TI - Predicting Negative Emotions Based on Mobile Phone Usage Patterns: An Exploratory
Study.
AB - BACKGROUND: Prompt recognition and intervention of negative emotions is crucial
for patients with depression. Mobile phones and mobile apps are suitable
technologies that can be used to recognize negative emotions and intervene if
necessary. OBJECTIVE: Mobile phone usage patterns can be associated with
concurrent emotional states. The objective of this study is to adapt machine
learning methods to analyze such patterns for the prediction of negative emotion.
METHODS: We developed an Android-based app to capture emotional states and mobile
phone usage patterns, which included call logs (and use of apps). Visual analog
scales (VASs) were used to report negative emotions in dimensions of depression,
anxiety, and stress. In the system-training phase, participants were requested to
tag their emotions for 14 consecutive days. Five feature-selection methods were
used to determine individual usage patterns and four machine-learning methods
were tested. Finally, rank product scoring was used to select the best
combination to construct the prediction model. In the system evaluation phase,
participants were then requested to verify the predicted negative emotions for at
least 5 days. RESULTS: Out of 40 enrolled healthy participants, we analyzed data
from 28 participants, including 30% (9/28) women with a mean (SD) age of 29.2
(5.1) years with sufficient emotion tags. The combination of time slots of 2
hours, greedy forward selection, and Naive Bayes method was chosen for the
prediction model. We further validated the personalized models in 18 participants
who performed at least 5 days of model evaluation. Overall, the predictive
accuracy for negative emotions was 86.17%. CONCLUSION: We developed a system
capable of predicting negative emotions based on mobile phone usage patterns.
This system has potential for ecological momentary intervention (EMI) for
depressive disorders by automatically recognizing negative emotions and providing
people with preventive treatments before it escalates to clinical depression.
PMID- 27511750
TI - Puffy feet in a female neonate.
PMID- 27511749
TI - Case of CML lymphoid blast crisis presenting as bilateral breast masses.
AB - A woman aged 42 years with a 1-month history of rapidly expanding bilateral
breast masses presented with severe leucocytosis, anaemia, blurry vision,
headaches and shortness of breath. Evaluation revealed chronic myeloid leukaemia
in lymphoid blast crisis with extramedullary leukaemia involving her breasts.
PMID- 27511751
TI - What is inside the hernia sac?
AB - Most ovarian inguinal hernias occur in children and are frequently associated
with congenital genitalia defects. The authors present the case of a multiparous
89-year-old woman, without any genitalia defect, who was brought to the emergency
department with an irreducible inguinal hernia. The patient was proposed for
emergency surgery during which we encountered an ovary and a fallopian tube
inside the hernial sac. An oophorosalpingectomy and a Lichtenstein procedure were
carried out and the postoperative period was uneventful. This case shows that,
even though it is rare, a hernial sac may contain almost any intra-abdominal
organ, including those least frequent such as the appendix, an ovary or the
fallopian tubes.
PMID- 27511752
TI - Haemophilia-A-related haematoma: management in resource constraint settings.
PMID- 27511753
TI - Peduncular psychosis.
AB - Psychotic symptoms are rarely documented in association with cortex-sparing
central nervous system (CNS) lesions limited to the midbrain. We present the case
of a 15-year-old boy with hereditary and environmental risk factors for
psychiatric illness, as well as a history of midbrain pilocytic astrocytoma
treated with chemotherapy and focused radiation, who presented with non-epileptic
seizures, hyper-religiosity and frank psychosis. The space-occupying midbrain
lesion has been radiographically stable while the patient has decompensated
psychiatrically. Differential aetiology for the patient's psychiatric
decompensation is discussed, including psychosis secondary to a lesion of the
midbrain. Literature linking midbrain lesions to psychotic features, such as in
peduncular hallucinosis, is briefly reviewed. This case suggests that a midbrain
lesion in a susceptible patient may contribute to psychosis.
PMID- 27511754
TI - Rapid recovery from catastrophic paraneoplastic anti-NMDAR encephalitis secondary
to an ovarian teratoma following ovarian cystectomy.
AB - This report is aimed to describe a life-threatening case of anti-N-methyl-d
aspartate receptor (NMDAR) encephalitis secondary to ovarian teratoma with rapid
recovery in 1 day after the removal of the tumour. A 23-year-old woman presented
with sudden headache, personality changes and seizure. After neurological
assessment, limbic or herpes encephalitis was provisionally diagnosed and treated
with intravenous immunoglobulin, acyclovir and steroids. The patient had
progressive severe neurological symptoms, requiring prolonged intubation and
mechanical ventilation. An anti-NMDAR antibody test revealed positive in serum
and cerebrospinal fluid at 3 weeks of admission. Pelvic ultrasound examination
and CT scan revealed bilateral small ovarian teratomas. Bilateral ovarian
cystectomy was performed by open surgery. The patient showed rapid improvement
and no longer needed intubation 2 days after the operation. In conclusion, we
described a catastrophic case of ovarian teratoma-associated encephalitis with
delayed diagnosis but rapid recovery after ovarian cystectomy. This information
can probably be helpful to neurologists and gynaecologists.
PMID- 27511755
TI - Single benign metastasising leiomyoma of an inguinal lymph node.
AB - Benign metastasising leiomyoma (BML) is a rare benign disease associated with
uterine leiomyoma and history of uterine surgery. It most frequently occurs in
premenopausal woman, with a pulmonary localisation, and consisting of multiple
nodules. We present an uncommon case of a 69-year-old woman with a single BML of
an inguinal lymph node. CT scans of thorax and abdomen excluded other metastasis
localisation. The patient was cured with surgical excision of the mass. Lymph
node involvement has been reported incidentally in BML literature. Lymphangitic
spread can be considered a possible mechanism of BML metastasis.
PMID- 27511756
TI - Spontaneous transvaginal small bowel evisceration 40 years post-abdominal
hysterectomy.
PMID- 27511758
TI - Russell body gastritis in an Hp-negative patient.
PMID- 27511759
TI - Gastric siderosis as a cause of dyspepsia.
PMID- 27511757
TI - Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.
AB - We describe two young immunocompetent women presenting with bilateral retinitis
with outer retinal necrosis involving posterior pole with centrifugal spread and
multifocal lesions simulating progressive outer retinal necrosis (PORN) like
retinitis. Serology was negative for HIV and CD4 counts were normal; however,
both women were on oral steroids at presentation for suspected autoimmune
chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir
therapy. However, the eye with the more fulminant involvement developed retinal
detachment with a loss of vision. Retinal atrophy was seen in the less involved
eye with preservation of vision. Through these cases, we aim to describe a unique
evolution of PORN-like retinitis in immunocompetent women, which was probably
aggravated by a short-term immunosuppression secondary to oral steroids.
PMID- 27511761
TI - Maternal mortality rates rise in US, study finds.
PMID- 27511760
TI - Interactions among Drosophila larvae before and during collision.
AB - In populations of Drosophila larvae, both, an aggregation and a dispersal
behavior can be observed. However, the mechanisms coordinating larval locomotion
in respect to other animals, especially in close proximity and during/after
physical contacts are currently only little understood. Here we test whether
relevant information is perceived before or during larva-larva contacts, analyze
its influence on behavior and ask whether larvae avoid or pursue collisions.
Employing frustrated total internal reflection-based imaging (FIM) we first found
that larvae visually detect other moving larvae in a narrow perceptive field and
respond with characteristic escape reactions. To decipher larval locomotion not
only before but also during the collision we utilized a two color FIM approach
(FIM(2c)), which allowed to faithfully extract the posture and motion of
colliding animals. We show that during collision, larval locomotion freezes and
sensory information is sampled during a KISS phase (german: Kollisions
Induziertes Stopp Syndrom or english: collision induced stop syndrome).
Interestingly, larvae react differently to living, dead or artificial larvae,
discriminate other Drosophila species and have an increased bending probability
for a short period after the collision terminates. Thus, Drosophila larvae
evolved means to specify behaviors in response to other larvae.
PMID- 27511762
TI - When Co-Authors Are Missing in Action.
PMID- 27511763
TI - Midwest Nursing Research Society News.
PMID- 27511764
TI - Development of a robust DNA quality and quantity assessment qPCR assay for
targeted next-generation sequencing library preparation.
AB - Next-generation sequencing (NGS) is becoming a standard for genetic analyses of
clinical samples. DNAs retrieved from formalin-fixed, paraffin-embedded (FFPE)
tissue specimens are commonly degraded, and specimens such as core biopsies are
sometimes too small to obtain enough DNA for NGS applications. Thus, it is
important to measure both the DNA quantity and quality accurately from clinical
samples. However, there is no standard method for DNA quantity and quality
analyses for NGS library preparation. We tested four different methods
(PicoGreen, Qubit(r) fluorometry, TaqMan and SYBR-Green-based qPCR assay) and
compared each to RNase P TaqMan as a reference control. We found that SYBR-Green
based qPCR assay provides a consistent and accurate DNA quantification while
keeping its cost relatively low and the throughput high. We designed a dual-probe
SYBR-Green qPCR assay for DNA quantity and quality assessment for targeted NGS
library preparation. This assay provides a Dscore (degradation score) of the
interrogated DNA by analyzing two different sizes of amplicons. We show an
example of a clinical sample with a very high Dscore (high degradation). With a
regular DNA quantification, without considering the degradation status, no
correct NGS libraries were obtained. However, after optimizing the library
condition by considering its poor DNA quality, a reasonably good library and
sequencing results were obtained. In summary, we developed and presented a new
DNA quantity and quality analysis qPCR assay for the targeted NGS library
preparation. This assay may be mostly efficient for the clinical samples with
high degradation and poor DNA quality.
PMID- 27511765
TI - A novel HLA-A*24 allele, HLA-A*24:325, identified in a Chinese individual.
AB - HLA-A*24:325 differs from A*24:02:01:01 by two nucleotide substitutions at
position 411 and 412.
PMID- 27511766
TI - Relationship of retinal vascular caliber variation with intracranial arterial
stenosis.
AB - BACKGROUND & PURPOSE: To investigate the associations of retinal vessel
parameters with intracranial arterial stenosis (ICAS) assessed by Transcranial
Doppler ultrasonography. METHOD: Data on transcranial Doppler ultrasonography and
quantitative retinal vessel parameters from 627 participants in a health
screening program were included in this study. ICAS was defined as >50%
intracranial arterial stenosis (ICAS) based on criteria modified from the stroke
outcomes and neuroimaging of intracranial atherosclerosis (SONIA) trial assessed
by transcranial Doppler (TCD) ultrasonography. A semi-automated computer-assisted
program (Singapore I Vessel Assessment) was used to measure the retinal vascular
parameters from the photographs. Multivariate analysis was performed to identify
which retinal vessel parameters were associated with increased risk of ICAS.
RESULTS: Among 627 participants, 24 (3.8%) had ICAS diagnosed by TCD. Subjects
with ICAS had eyes with wider mean central retinal artery equivalent (CRAE) and
central retinal vein equivalent (CRVE) in comparison to subjects without ICAS.
Men (odds ratio [OR]:13.1, 95% confidence interval: 3.13-33.33) and a large
standard deviation of mean arterial width (STDWa) were associated with ICAS
(first vs. third tertile: OR ratio: 14.04, 95% confidence interval: 1.71-115.32;
first vs. third tertile: OR ratio: 22.1, 95% confidence interval: 2.56-190.97)
after adjusting for possible confounders. CONCLUSION: A large variation in
retinal arteriolar diameter is associated with ICAS. This study suggests the
possible relationship between retina vessel and early changes within the
cerebrovascular network.
PMID- 27511767
TI - Lung cancer: despite advances, prevention is still best.
PMID- 27511768
TI - Argentina acts on violence against women and girls.
PMID- 27511769
TI - Reassessing blood donation by men who have sex with men.
PMID- 27511770
TI - The unfinished race: 30 years of gender verification in sport.
PMID- 27511772
TI - Unresolved issues in Canada's law on physician-assisted dying.
PMID- 27511771
TI - Finding a balance: Canada's law on medical assistance in dying.
PMID- 27511773
TI - Reducing research waste with implementation laboratories.
PMID- 27511776
TI - Clinical examination nowadays.
PMID- 27511774
TI - Drug scandals in France: have the lessons been learnt?
PMID- 27511777
TI - The first recorded use of microscopy in medicine: Pope Innocent XII's autopsy
report.
PMID- 27511778
TI - Risk factors for neonatal disorders and the Global Burden of Disease.
PMID- 27511779
TI - Mental illness: the forgotten burden on diabetes populations?
PMID- 27511780
TI - Freedom of expression and health: is the association causal?
PMID- 27511781
TI - Increasing value and reducing waste in biomedical research.
PMID- 27511782
TI - Foot print of a paper: accountability in academic publishing.
PMID- 27511783
TI - Academic apartheid in Italy.
PMID- 27511784
TI - The benefits of screening--and its harms.
PMID- 27511785
TI - The CHAMPION trial outcomes were not adequately prespecified.
PMID- 27511786
TI - Department of Error.
PMID- 27511787
TI - Renal apnoea: extreme disturbance of homoeostasis in a child with Bartter
syndrome type IV.
PMID- 27511788
TI - The importance of being rare.
PMID- 27511789
TI - Cardiac Risk and Disordered Eating: Decreased R Wave Amplitude in Women with
Bulimia Nervosa and Women with Subclinical Binge/Purge Symptoms.
AB - The purpose of the present study was threefold. First, we examined whether women
with bulimia nervosa (n = 12) and women with subthreshold binge/purge symptoms (n
= 20) showed decreased mean R wave amplitude, an indicator of cardiac risk, on
electrocardiograph compared to asymptomatic women (n = 20). Second, we examined
whether this marker was pervasive across experimental paradigms, including before
and after sympathetic challenge tasks. Third, we investigated behavioural
predictors of this marker, including binge frequency and purge frequency assessed
by subtype (dietary restriction, excessive exercise, self-induced vomiting, and
laxative abuse). Results of a 3 (ED symptom status) * 5 (experimental condition)
mixed factorial ANCOVA (covariates: body mass index, age) indicated women with
bulimia nervosa and women with subclinical binge/purge symptoms demonstrated
significantly reduced mean R wave amplitude compared to asymptomatic women; this
effect was pervasive across experimental conditions. Multiple regression analyses
showed binge and purge behaviours, most notably laxative abuse as a purge method,
predicted decreased R wave amplitude across all experimental conditions.
Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 27511790
TI - Modeling functional decline over time in sporadic inclusion body myositis.
AB - INTRODUCTION: The ability to individualize recommendations or expectations of
disease progression based on a patient's unique characteristics has merit for use
in sporadic inclusion body myositis (sIBM). METHODS: Fifty-five subjects with
sIBM completed a battery of strength and functional outcomes at 2 study visits.
These were used to develop mathematical models of disease progression in patients
with sIBM for use in clinical and research settings. RESULTS: The 6-minute walk
test (6MWT) distance declined by an average of 27.5 meters (12%) per year.
Significant factors that predict 6MWT were knee extension and plantarflexion
strength and body weight, whereas the ability to stand from a chair was impacted
by elbow extension strength. Stepping up on a curb was influenced by the
patient's age at diagnosis and by knee extension. Statistical models to predict
functional decline in sIBM were developed. CONCLUSION: Statistical models help
explain the complex factors that influence decreased walking ability and other
functional activities in sIBM. Muscle Nerve 55: 526-531, 2017.
PMID- 27511791
TI - The initial break-up of Pangaea elicited by Late Palaeozoic deglaciation.
AB - The break-up of Pangaea was principally facilitated by tensional plate stress
acting on pre-existing suture zones. The rifting of Pangaea began during the
Early Permian along the southern Tethys margin and produced the lenticular-shaped
continent known as Cimmeria. A mantle-plume model is ascribed to explain the rift
related volcanism but the NW-SE oriented Cimmerian rifts do not correlate well
with pre-existing suture zones or 'structural heterogeneities' but appear to have
a pertinent spatial and temporal association with Late Palaeozoic glacial
interglacial cycles. Mantle potential temperature estimates of Cimmerian rift
related basalts (1410 degrees C +/- 50 degrees C) are similar to ambient mantle
conditions rather than an active mantle-plume rift as previously suggested.
Moreover, we find that the distribution of glacial deposits shows significant
temporal and spatial concurrence between the glacial retreat margins and rifting
sites. We conclude that the location and timing of Cimmerian rifting resulted
from the exploitation of structural heterogeneities within the crust that formed
due to repeated glacial-interglacial cycles during the Late Palaeozoic. Such
effects of continental deglaciation helped to create the lenticular shape of
Cimmeria and Neotethys Ocean suggesting that, in some instances, climate change
may directly influence the location of rifting.
PMID- 27511792
TI - Increasing Lower Extremity Injury Rates Across the 2009-2010 to 2014-2015 Seasons
of National Collegiate Athletic Association Football: An Unintended Consequence
of the "Targeting" Rule Used to Prevent Concussions?
AB - BACKGROUND: Sports-related concussions (SRCs) have gained increased societal
interest in the past decade. The National Collegiate Athletic Association (NCAA)
has implemented legislation and rule changes to decrease the incidence and risk
of head injury impacts. The "targeting" rule forbids initiating contact with the
crown of a helmet and targeting defenseless players in the head and neck area;
however, there are concerns that this rule change has unintentionally led to an
increased incidence of lower extremity injuries. PURPOSE/HYPOTHESIS: The purpose
of this study was to evaluate the change in lower extremity injury rates in NCAA
football during the 2009-2010 to 2014-2015 seasons. We hypothesized that the
lower extremity injury rate has increased across the time period. STUDY DESIGN:
Descriptive epidemiology study. METHODS: Sixty-eight NCAA football programs
provided 153 team-seasons of data to the NCAA Injury Surveillance Program. Lower
extremity injuries (ie, hip/groin, upper leg/thigh, knee, lower leg/Achilles,
foot/toes) and SRCs sustained during NCAA football games were examined. We
calculated injury rates per 1000 athlete-exposures (AEs) for lower extremity
injuries and SRCs. Rate ratios (RRs) compared injury rates between the 2009-2010
to 2011-2012 and 2012-2013 to 2014-2015 seasons. RESULTS: Overall, 2400 lower
extremity injuries were reported during the 2009-2010 to 2014-2015 seasons; most
were to the knee (33.6%) and ankle (28.5%) and caused by player contact (59.2%).
The lower extremity injury rate increased in 2012-2013 to 2014-2015 compared with
2009-2010 to 2011-2012 (23.55 vs 20.45/1000 AEs, respectively; RR, 1.15; 95% CI,
1.06-1.25). This finding was retained when restricted to injuries due to player
contact (RR, 1.19; 95% CI, 1.07-1.32) but not for injuries due to
noncontact/overuse (RR, 0.96; 95% CI, 0.80-1.14). When examining player contact
injury rates by anatomic site, only ankle injuries had an increase (RR, 1.36; 95%
CI, 1.13-1.64). The SRC rate also increased in 2012-2013 to 2014-2015 compared
with 2009-2010 to 2011-2012 (3.52 vs 2.63/1000 AEs, respectively; RR, 1.34; 95%
CI, 1.08-1.66). CONCLUSION: The lower extremity injury rate has increased in NCAA
football athletes. Similarly, SRC rates have increased, although this may be
caused by concurrent policies related to better education, identification, and
management. Targeting rule changes may be contributing to increased rates of
player contact-related ankle injuries. Alongside continued surveillance research
to examine longitudinal time trends, more in-depth individual-level examinations
of how targeting rule changes influence coaching and player behaviors are
warranted.
PMID- 27511793
TI - Anterior Cruciate Ligament Injuries Alter the Kinematics of Knees With or Without
Meniscal Deficiency.
AB - BACKGROUND: Numerous studies have investigated kinematic alterations in patients
with an isolated anterior cruciate ligament (ACL) injury. However, a substantial
proportion of patients with injured ACLs also have concomitant meniscal tears.
PURPOSE: To evaluate the in vivo alteration of knee kinematics after an ACL tear,
with or without a combined medial or lateral meniscal tear, during level walking
activity. STUDY DESIGN: Controlled laboratory study. METHODS: Fifty-six patients
with unilateral ACL-deficient (ACLD) knees were studied. Among these patients, 15
had isolated ACL injuries (group 1), 15 had combined ACL and medial meniscal
injuries (group 2), 15 had combined ACL and lateral meniscal injuries (group 3),
and 11 had combined ACL and medial/lateral meniscal injuries (group 4). The
kinematics of each knee was determined using an optical tracking system during
treadmill gait. Range of motion (ROM) and kinematic alterations were compared
between the contralateral ACL-intact (ACLI) and ACLD knees. RESULTS: All ACLD
knees, with or without meniscal deficiency, had significantly less flexion than
the ACLI knees (~3 degrees -8 degrees ; P < .05). In groups 1, 3, and 4, the
injured knees exhibited more femoral external rotation by approximately 1 degrees
to 2 degrees (P < .05). Group 4 showed posterior femoral translation (anterior
tibial translation) in the swing phase (~13 mm), while groups 2 and 3 showed
increased anterior femoral translation (~2-3 mm). During medial-lateral
translation, patients in group 2 had a more medial femoral shift (~4 mm) relative
to the tibia initially, while those in group 4 exhibited a lateral femoral shift.
CONCLUSION: The results indicate that meniscal injuries alter the kinematics of
the ACLD knee when compared with knees with an isolated ACL injury. The location
of the meniscal tear also affects knee kinematics. CLINICAL RELEVANCE:
Considering the varying effects of meniscal injuries on knee joint kinematics,
these data provide insight into the pathological function of the ACL-injured knee
joint during walking.
PMID- 27511794
TI - tRNA Shifts the G-quadruplex-Hairpin Conformational Equilibrium in RNA towards
the Hairpin Conformer.
AB - Non-coding RNAs play important roles in cellular homeostasis and are involved in
many human diseases including cancer. Intermolecular RNA-RNA interactions are the
basis for the diverse functions of many non-coding RNAs. Herein, we show how the
presence of tRNA influences the equilibrium between hairpin and G-quadruplex
conformations in the 5' untranslated regions of oncogenes and model sequences.
Kinetic and equilibrium analyses of the hairpin to G-quadruplex conformational
transition of purified RNA as well as during co-transcriptional folding indicate
that tRNA significantly shifts the equilibrium toward the hairpin conformer. The
enhancement of relative translation efficiency in a reporter gene assay is shown
to be due to the tRNA-mediated shift in hairpin-G-quadruplex equilibrium of
oncogenic mRNAs. Our findings suggest that tRNA is a possible therapeutic target
in diseases in which RNA conformational equilibria is dysregulated.
PMID- 27511795
TI - Cross-validated stable-isotope dilution GC-MS and LC-MS/MS assays for
monoacylglycerol lipase (MAGL) activity by measuring arachidonic acid released
from the endocannabinoid 2-arachidonoyl glycerol.
AB - 2-Arachidonoyl glycerol (2AG) is an endocannabinoid that activates cannabinoid
(CB) receptors CB1 and CB2. Monoacylglycerol lipase (MAGL) inactivates 2AG
through hydrolysis to arachidonic acid (AA) and glycerol, thus modulating the
activity at CB receptors. In the brain, AA released from 2AG by the action of
MAGL serves as a substrate for cyclooxygenases which produce pro-inflammatory
prostaglandins. Here we report stable-isotope GC-MS and LC-MS/MS assays for the
reliable measurement of MAGL activity. The assays utilize deuterium-labeled 2AG
(d8-2AG; 10MUM) as the MAGL substrate and measure deuterium-labeled AA (d8-AA;
range 0-1MUM) as the MAGL product. Unlabelled AA (d0-AA, 1MUM) serves as the
internal standard. d8-AA and d0-AA are extracted from the aqueous buffered
incubation mixtures by ethyl acetate. Upon solvent evaporation the residue is
reconstituted in the mobile phase prior to LC-MS/MS analysis or in anhydrous
acetonitrile for GC-MS analysis. LC-MS/MS analysis is performed in the negative
electrospray ionization mode by selected-reaction monitoring the mass transitions
[M-H]-->[M-H - CO2]-, i.e., m/z 311->m/z 267 for d8-AA and m/z 303->m/z 259 for
d0-AA. Prior to GC-MS analysis d8-AA and d0-AA were converted to their
pentafluorobenzyl (PFB) esters by means of PFB-Br. GC-MS analysis is performed in
the electron-capture negative-ion chemical ionization mode by selected-ion
monitoring the ions [M-PFB]-, i.e., m/z 311 for d8-AA and m/z 303 for d0-AA. The
GC-MS and LC-MS/MS assays were cross-validated. Linear regression analysis
between the concentration (range, 0-1MUM) of d8-AA measured by LC-MS/MS (y) and
that by GC-MS (x) revealed a straight line (r2=0.9848) with the regression
equation y=0.003+0.898x, indicating a good agreement. In dog liver, we detected
MAGL activity that was inhibitable by the MAGL inhibitor JZL-184. Exogenous
eicosatetraynoic acid is suitable as internal standard for the quantitative
determination of d8-AA produced from d8-2AG by hepatic MAGL activity. The
formation of d8-prostaglandin E2 by the consecutive catalytic action of
recombinant MAGL on d8-2AG and recombinant cyclooxygenase-2 (COX) on d8-AA was
demonstrated by GC-MS/MS.
PMID- 27511796
TI - Hypertension and risk of prostate cancer: a systematic review and meta-analysis.
AB - The previously reported association between hypertension and prostate cancer risk
was controversial. We performed this systematic review and meta-analysis of all
available studies to summarize evidence on this association. Studies were
identified by searching PubMed, Web of Science and Chinese National Knowledge
Infrastructure (CNKI) databases through January 2016. Pooled relative risks (RRs)
with their corresponding 95% confidence intervals (CIs) were calculated using a
random-effects model. A total of 21 published studies were included in this meta
analysis. A significant increase in the risk of prostate cancer (RR 1.08, 95% CI
1.02-1.15, P = 0.014) was observed among individuals with hypertension. There was
statistically significant heterogeneity among included studies (P < 0.001 for
heterogeneity, I(2) = 72.1%). No obvious evidence of significant publication bias
was detected by either Begg's test (P = 0.174) or Egger's test (P = 0.277). In
conclusion, this meta-analysis indicates that hypertension may be associated with
an increased risk of prostate cancer. Considering the substantial heterogeneity
and residual confounding among included studies, further large-scale, well
designed prospective cohorts, as well as mechanistic studies, are urgently needed
to confirm our preliminary findings.
PMID- 27511797
TI - Comparative study of skin autofluorescence expression in atopic dermatitis and
psoriasis: A prospective in vivo study.
AB - BACKGROUND/PURPOSE: Treatment of atopic dermatitis (AD) and psoriasis requires
their differentiation from other eczematoid dermatitis and a determination of
disease severity. However, both can be clinically difficult and the findings
subjectively interpreted. We investigated the utility of in vivo autofluorescence
(AF) measurements for diagnosis of both diseases, and determination of severity.
MATERIALS AND METHODS: Thirty patients with AD and 30 with psoriasis were
recruited, together with sex- and age-matched patients with healthy skin. AF
intensity was measured using the EcoSkin(r) fluorescence video dermatoscope. In
AD and psoriasis patients, AF in non-sun-exposed lesional and non-lesional skin
was measured. To identify the locations that reflect characteristics of AD, AF
was also measured at the other sites in the patients with AD. RESULTS: AD was
associated with lower AF and psoriasis with higher AF intensity peaking around
620 nm. In addition, skin AF intensity of each disease was associated with
severity of lesion. CONCLUSIONS: Non-invasive measurement of skin AF in vivo can
aid in diagnosis of AD and psoriasis as well as in treatment monitoring.
PMID- 27511798
TI - Characterization of polymeric pigments and pyranoanthocyanins formed in
microfermentations of non-Saccharomyces yeasts.
AB - AIMS: To assess the influence of non-Saccharomyces yeasts on the
pyranoanthocyanins and polymeric pigments formation after the addition of (+)
catechin and procyanidin B2 to fresh red grape must. METHODS AND RESULTS: The
fermentation of red grape musts was done with non-Saccharomyces yeasts either
alone or in sequential fermentations with the Saccharomyces cerevisiae species.
The characterization of both pyranoanthocyanin and polymeric pigments has been
carried out with liquid chromatography coupled to mass spectroscopy (HPLC-DAD
ESI/MS). Red wines were also characterized by infrared spectroscopy (FTIR), gas
chromatography (GC-FID) and spectrophotometry (UV-Vis). It has been observed that
fermentation with the species Schizosaccharomyces pombe led to higher
concentrations of pigments of all types: anthocyanins, polymeric pigments and
pyranoanthocyanins, particularly vitisin A. CONCLUSIONS: The use of non
Saccharomyces yeasts improve the formation of stable pigments in red wines thanks
to the differences in the microbial metabolism from among the yeasts studied.
SIGNIFICANCE AND IMPACT OF THE STUDY: Colour stability as one of the main
organoleptic properties in red wines, may be improved by the controlled use of
selected non-Saccharomyces yeasts during red must fermentation.
PMID- 27511799
TI - Heroin overdose.
AB - BACKGROUND AND AIMS: This narrative review aims to provide a brief history of the
development of the heroin overdose field by discussing a selection of major
'classics' from the latter part of the 20th century. METHODS: Papers considered
landmarks were selected from 1972, 1977, 1983, 1984 and 1999. RESULTS: Findings
of earlier works suggest much of what later research was to demonstrate. These
include arguing that overdoses occurred primarily among tolerant older users,
that most 'overdose' deaths involved low morphine concentrations, that most
overdoses involve polypharmacy, that drug purity has only a moderate influence on
overdose rates and that instant death following heroin administration is rare.
CONCLUSIONS: Landmark studies of heroin overdose from the 1970s, 1980s and 1990s
laid the foundations for subsequent overdose research, mainly by identifying the
major demographic characteristics of overdose cases, risk factors, survival times
and behaviours at overdose events.
PMID- 27511801
TI - Solubility-driven toxicity of CuO nanoparticles to Caco2 cells and Escherichia
coli: Effect of sonication energy and test environment.
AB - Due to small size and high surface energy nanoparticles (NPs) tend to agglomerate
and precipitate. To avoid/diminish that, sonication of NPs stock suspensions
prior toxicity testing is often applied. Currently, there is no standardized
particle sonication protocol available leading to inconsistent toxicity data,
especially if toxicity is driven by NPs' dissolution that may be enhanced by
sonication. In this study we addressed the effect of sonication on hydrodynamic
size (Dh), dissolution and toxicity of copper oxide (CuO) NPs to mammalian cell
line Caco-2 in vitro and bacteria Escherichia coli in the respective test
environments (cell culture MEM medium, bacterial LB medium and deionised (DI)
water). NPs were suspended using no sonication, water bath and probe sonication
with different energy intensities. Increased sonication energy (i) decreased the
Dh of CuO NPs in all three test environments; (ii) increased dissolution of NPs
in MEM medium and their toxicity to Caco-2; (iii) increased dissolution of NPs in
LB medium and their bioavailability to E. coli; and (iv) had no effect on
dissolution and antibacterial effects of NPs in DI water. Thus, to reduce
variations in dissolution and toxicity, we recommend sonication of NPs in DI
water following the dilution into suitable test media.
PMID- 27511800
TI - The presence of macrophages and inflammatory responses in an in vitro testicular
co-culture model of male reproductive development enhance relevance to in vivo
conditions.
AB - Our 3-dimensional testis co-culture system (3D-TCS) represents a promising model
of male reproductive toxicity which captures sensitive processes of male
reproductive development and contains the main testes cell types (germ, Leydig
and Sertoli cells). Macrophages are another cell type important for testicular
function and help to modulate immuno-endocrine processes during testes
development. Chemicals such as phthalate esters (PE's) affect macrophage function
and testosterone production in the testes in vivo. The aim of this study was to
determine whether macrophages were present in the 3D-TCS and investigate
responses in our model that may be related to immuno-endocrine functions. We
observed consistent expression of the resident macrophage marker ED2 as well as
increases in inflammatory cytokines produced by macrophages and testes cells (IL
6, TNF-alpha and KC/GRO) after exposure to toxic PE's. Pathway analysis of gene
expression changes after exposure to PE's showed that IL-6 and TNF-alpha
signaling pathways were enriched after treatment with reproductively toxic, but
not non-reproductively toxic phthalates. These results indicate that macrophages
and inflammatory processes are captured in the 3D-TCS and that these processes
are impacted by exposure to reproductive toxicants. These processes represent a
major mode of action for in vivo testis toxicity for a variety of compounds and
our novel in vitro model is able to capture toxicant perturbation of immune
function.
PMID- 27511802
TI - Pd-catalyzed cascade allylic alkylation and dearomatization reactions of indoles
with vinyloxirane.
AB - We have developed Pd-catalyzed intermolecular Friedel-Crafts-type allylic
alkylation and allylic dearomatization reactions of substituted indoles bearing a
nucleophilic group with vinyloxirane, providing an efficient method to synthesize
structurally diverse tetrahydrocarboline and spiroindolenine derivatives under
mild conditions.
PMID- 27511803
TI - Radical-scavenging activity of penicillin G, ampicillin, oxacillin, and
dicloxacillin.
AB - The aim of this study was to characterize the antioxidant activity of penicillin
G (PG), ampicillin (AMP), oxacillin (OX) and dicloxacillin (DOX) through their
reactivity towards reactive oxygen species (superoxide anion radical, O2*;
hydroxyl radical, HO* ; peroxyl radical, ROO* ; hydrogen peroxide, H2 O2 ; DPPH*
) using various in vitro antioxidant assays with chemiluminescence (CL) and
spectrophotometry as measurement techniques. In hydroxyl radical assays , PG, OX
and AMP were found to inhibit the CL signal arising from the Fenton-like reaction
in a dose-dependent manner with IC50 = 0.480 +/- 0.020 mM, IC50 = 0.569 +/-
0.021 mM, and IC50 = 0.630 +/- 0.019 mM, respectively. The highest reactivity of
PG among the tested penicillins towards the HO radical was confirmed in the
deoxyribose degradation assay. In the ABAP-derived ROO radical assay, the radical
scavenging ability of the test penicillins was in the following order: AMP > PG >
DOX > OX. The number of reduced DPPH radicals by the drugs tested was <1 being
the biggest for PG. The weak antioxidant capacity of the test penicillins was
confirmed in the trolox antioxidant capacity assay (0.075 +/- 0.004; 0.093 +/-
0.006; 0.123 +/- 0.005; 0.126 +/- 0.004) for OX, AMP, DOX, PG, respectively. Use
of luminol as a CL probe for estimation of penicillin reactivity towards H2 O2
showed that only AMP was able to quench light emission; the remaining antibiotics
demonstrated a strong enhancing effect. All the examined compounds showed a weak
antioxidant potential when estimated using the ferric-ferrozine assay. This study
is the first to report the evaluation of test penicillins as antioxidants under
the same reaction conditions.
PMID- 27511804
TI - Contact Resistance Effects in Highly Doped Organic Electrochemical Transistors.
AB - Injection at the source contact critically determines the behavior of depletion
type organic electrochemical transistors (OETs). The contact resistance of OETs
increases exponentially with the gate voltage and strongly influences the
modulation of the drain current by the gate voltage over a wide voltage range. A
modified standard model accounting contact resistance can explain the particular
shape of the transconductance.
PMID- 27511806
TI - Macromolecular structure phasing by neutron anomalous diffraction.
AB - In this report we show for the first time that neutron anomalous dispersion can
be used in a practical manner to determine experimental phases of a protein
crystal structure, providing a new tool for structural biologists. The approach
is demonstrated through the use of a state-of-the-art monochromatic neutron
diffractometer at the Institut Laue-Langevin (ILL) in combination with crystals
of perdeuterated protein that minimise the level of hydrogen incoherent
scattering and enhance the visibility of the anomalous signal. The protein used
was rubredoxin in which cadmium replaced the iron at the iron-sulphur site. While
this study was carried out using a steady-state neutron beam source, the results
will be of major interest for capabilities at existing and emerging spallation
neutron sources where time-of-flight instruments provide inherent energy
discrimination. In particular this capability may be expected to offer unique
opportunities to a rapidly developing structural biology community where there is
increasing interest in the identification of protonation states, protein/water
interactions and protein-ligand interactions - all of which are of central
importance to a wide range of fundamental and applied areas in the biosciences.
PMID- 27511807
TI - Experimental realization of stimulated Raman shortcut-to-adiabatic passage with
cold atoms.
AB - Accurate control of a quantum system is a fundamental requirement in many areas
of modern science ranging from quantum information processing to high-precision
measurements. A significantly important goal in quantum control is preparing a
desired state as fast as possible, with sufficiently high fidelity allowed by
available resources and experimental constraints. Stimulated Raman adiabatic
passage (STIRAP) is a robust way to realize high-fidelity state transfer but it
requires a sufficiently long operation time to satisfy the adiabatic criteria.
Here we theoretically propose and then experimentally demonstrate a shortcut-to
adiabatic protocol to speed-up the STIRAP. By modifying the shapes of the Raman
pulses, we experimentally realize a fast and high-fidelity stimulated Raman
shortcut-to-adiabatic passage that is robust against control parameter
variations. The all-optical, robust and fast protocol demonstrated here provides
an efficient and practical way to control quantum systems.
PMID- 27511808
TI - Correlation between antimicrobial consumption and antimicrobial resistance of
Pseudomonas aeruginosa in a hospital setting: a 10-year study.
AB - WHAT IS KNOWN AND OBJECTIVE: Antimicrobial resistance is one of the greatest
threats to human health. One of the most important factors leading to the
emergence of resistant bacteria is overuse of antibiotics. The purpose of this
study was to investigate the correlation between antimicrobial usage and
bacterial resistance of Pseudomonas aeruginosa (P. aeruginosa) over a 10-year
period in the Clinical Center Nis, one of the biggest tertiary care hospitals in
Serbia. We focused on possible relationships between the consumption of
carbapenems and beta-lactam antibiotics and the rates of resistance of P.
aeruginosa to carbapenems. METHODS: We recorded utilization of antibiotics
expressed as defined daily doses per 100 bed days (DBD). Bacterial resistance was
reported as the percentage of resistant isolates (percentage of all resistant and
intermediate resistant strains) among all tested isolates. RESULTS AND
DISCUSSION: A significant increasing trend in resistance was seen in imipenem (P
< 0.05, Spearman rho = 0.758) and meropenem (P < 0.05, rho = 0.745). We found a
significant correlation between aminoglycoside consumption and resistance to
amikacin (P < 0.01, Pearson r = 0.837) and gentamicin (P < 0.01, Pearson r =
0.827). The correlation between the consumption of carbapenems and resistance to
imipenem in P. aeruginosa shows significance (P < 0.01, Pearson r = 0.795),
whereas resistance to meropenem showed a trend towards significance (P > 0.05,
Pearson r = 0.607). We found a very good correlation between the use of all beta
lactam and P. aeruginosa resistance to carbapenems (P < 0.01, Pearson r = 0.847
for imipenem and P < 0.05, Pearson r = 0.668 for meropenem). WHAT IS NEW AND
CONCLUSION: Our data demonstrated a significant increase in antimicrobial
resistance to carbapenems, significant correlations between the consumption of
antibiotics, especially carbapenems and beta-lactams, and rates of antimicrobial
resistance of P. aeruginosa to imipenem and meropenem.
PMID- 27511810
TI - Single, community-based blood glucose readings may be a viable alternative for
community surveillance of HbA1c and poor glycaemic control in people with known
diabetes in resource-poor settings.
AB - BACKGROUND: The term HbA1c (glycated haemoglobin) is commonly used in relation to
diabetes mellitus. The measure gives an indication of the average blood sugar
levels over a period of weeks or months prior to testing. For most low- and
middle-income countries HbA1c measurement in community surveillance is
prohibitively expensive. A question arises about the possibility of using a
single blood glucose measure for estimating HbA1c and therefore identifying poor
glycaemic control in resource-poor settings. DESIGN: Using data from the 2011
2012 US National Health and Nutrition Examination Surveys, we examined the
relationship between HbA1c and a single fasting measure of blood glucose in a non
clinical population of people with known diabetes (n=333). A linear equation for
estimating HbA1c from blood glucose was developed. Appropriate blood glucose cut
off values were set for poor glycaemic control (HbA1c>=69.4 mmol/mol). RESULTS:
The HbA1c and blood glucose measures were well correlated (r=0.7). Three blood
glucose cut-off values were considered for classifying poor glycaemic control:
8.0, 8.9, and 11.4 mmol/L. A blood glucose of 11.4 had a specificity of 1, but
poor sensitivity (0.37); 8.9 had high specificity (0.94) and moderate sensitivity
(0.7); 8.0 was associated with good specificity (0.81) and sensitivity (0.75).
CONCLUSIONS: Where HbA1c measurement is too expensive for community surveillance,
a single blood glucose measure may be a reasonable alternative. Generalising the
specific results from these US data to low resource settings may not be
appropriate, but the general approach is worthy of further investigation.
PMID- 27511809
TI - The management of anovulatory infertility in women with polycystic ovary
syndrome: an analysis of the evidence to support the development of global WHO
guidance.
AB - BACKGROUND: Here we describe the consensus guideline methodology, summarise the
evidence-based recommendations we provided to the World Health Organisation (WHO)
for their consideration in the development of global guidance and present a
narrative review on the management of anovulatory infertility in women with
polycystic ovary syndrome (PCOS). OBJECTIVE AND RATIONALE: The aim of this paper
was to present an evidence base for the management of anovulatory PCOS. SEARCH
METHODS: The evidence to support providing recommendations involved a
collaborative process for: (i) identification of priority questions and critical
outcomes, (ii) retrieval of up-to-date evidence and exiting guidelines, (iii)
assessment and synthesis of the evidence and (iv) the formulation of draft
recommendations to be used for reaching consensus with a wide range of global
stakeholders. For each draft recommendation, the methodologist evaluated the
quality of the supporting evidence that was then graded as very low, low,
moderate or high for consideration during consensus. OUTCOMES: Evidence was
synthesized and we made recommendations across the definition of PCOS including
hyperandrogenism, menstrual cycle regulation and ovarian assessment. Metabolic
features and the impact of ethnicity were covered. Management includes lifestyle
changes, bariatric surgery, pharmacotherapy (including clomiphene citrate (CC),
aromatase inhibitors, metformin and gonadotropins), as well as laparoscopic
surgery. In-vitro fertilization (IVF) was considered as were the risks of
ovulation induction and of pregnancy in PCOS. Approximately 80% of women who
suffer from anovulatory infertility have PCOS. Lifestyle intervention is
recommended first in women who are obese largely on the basis of general health
benefits. Bariatric surgery can be considered where the body mass index (BMI) is
>=35 kg/m2 and lifestyle therapy has failed. Carefully conducted and monitored
pharmacological ovulation induction can achieve good cumulative pregnancy rates
and multiple pregnancy rates can be minimized with adherence to recommended
protocols. CC should be first-line pharmacotherapy for ovulation induction and
letrozole can also be used as first-line therapy. Metformin alone has limited
benefits in improving live birth rates. Gonadotropins and laparoscopic surgery
can be used as second-line treatment. There is no clear evidence for efficacy of
acupuncture or herbal mixtures in women with PCOS. For women with PCOS who fail
lifestyle and ovulation induction therapy or have additional infertility factors,
IVF can be used with the safer gonadotropin releasing hormone (GnRH) antagonist
protocol. If a GnRH-agonist protocol is used, metformin as an adjunct may reduce
the risk of ovarian hyperstimulation syndrome. Patients should be informed of the
potential side effects of ovulation induction agents and of IVF on the foetus,
and of the risks of multiple pregnancy. Increased risks for the mother during
pregnancy and for the child, including the exacerbating impact of obesity on
adverse outcomes, should also be discussed. WIDER IMPLICATIONS: This guidance
generation and evidence-synthesis analysis has been conducted in a manner to be
considered for global applicability for the safe administration of ovulation
induction for anovulatory women with PCOS.
PMID- 27511812
TI - A giant anguilliform leptocephalus Thalassenchelys foliaceus Castle & Raju is a
junior synonym of Congriscus maldivensis (Norman 1939).
AB - A single specimen of giant leptocephalus Thalassenchelys foliaceus Castle & Raju
1975 was caught in subtropical waters of the western North Pacific Ocean.
Mitochondrial coI gene sequence divergence between T. foliaceus and Congriscus
maldivensis (Norman 1939) was 0.64 +/- 0.27% (mean +/- s.e.), and the myomere and
vertebral counts of these species were similar, indicating T. foliaceus is a
junior synonym of C. maldivensis.
PMID- 27511811
TI - The impact of a livelihood program on depressive symptoms among people living
with HIV in Cambodia.
AB - BACKGROUND: Psychological and social problems are major concerns in this era of
successful antiretroviral therapy. Although livelihood programs have been
implemented extensively to improve the daily living conditions of people living
with HIV in Cambodia, no studies have yet investigated the impacts of these
programs on the mental health of this vulnerable population. Therefore, we
examined the impact of a livelihood program on depressive symptoms and associated
factors among people living with HIV in Cambodia. DESIGN: A quasi-experimental,
nonequivalent comparison group study was conducted in six provinces of Cambodia
in 2014. Data were collected from an intervention group comprising 357 people
living with HIV who had participated in the livelihood program and a comparison
group comprising 328 people living with HIV who had not participated in this
program. Multiple logistic regression analysis was carried out to examine the
association between livelihood-program participation and depressive symptoms as
measured by the depressive symptoms subscale of the 25-item Cambodian version of
the Hopkins Symptom Checklist. A propensity score matching was used to examine
the effect of the livelihood program on depressive symptoms while controlling for
selection bias. RESULTS: Overall, 56.0% and 62.7% of the participants in the
intervention and comparison groups, respectively, met the Hopkins Symptom
Checklist threshold for depressive symptoms. The multiple logistic regression
analysis showed that the participants in the intervention group had significantly
lower odds of having depressive symptoms (adjusted odds ratio 0.68, 95%
confidence interval 0.52-0.88). The analysis from propensity score matching
indicated that the livelihood program helped mitigate depressive symptoms among
the participants in the intervention group (T=-1.99). CONCLUSIONS: The livelihood
program appeared to help mitigate the burden of depressive symptoms among people
living with HIV in Cambodia. Thus, this program should be scaled up and modified
to better improve participants' mental health.
PMID- 27511813
TI - Association Between Train-of-Four Values and Gas Exchange Indices in Moderate to
Severe Acute Respiratory Distress Syndrome.
AB - BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with a
mortality rate of approximately 40%. Neuromuscular blockade is associated with an
improvement in oxygenation and a reduction in mortality in ARDS. OBJECTIVE: The
goal of this evaluation was to determine if the depth of paralysis, determined by
train-of-four (TOF) monitoring, correlates with gas exchange in moderate to
severe ARDS. METHODS: This was a retrospective review of moderate to severe ARDS
patients who were prescribed >12 hours of continuous infusion cisatracurium
between January 1, 2013, and December 31, 2014, with a PaO2:FiO2 ratio <150 and
documented TOF and arterial blood gases. Patients were evaluated for inclusion at
12, 24, and 48 hours after initiation of neuromuscular blockade. RESULTS: A total
of 378 patients were screened for inclusion, with 107 evaluable patients meeting
criteria at baseline. Poor correlation existed between TOF and oxygenation index
(OI) at 12 (tau = 0.03), 24 (tau = 0.15) and 48 hours (tau = 0.08). When
controlling for proning and baseline OI, the depth of paralysis did not have a
significant effect on OI at 12, 24, or 48 hours. CONCLUSIONS: This evaluation
demonstrates that the use of TOF monitoring for neuromuscular blockade does not
correlate with gas exchange markers in moderate to severe ARDS.
PMID- 27511814
TI - Methotrexate Elimination When Coadministered With Levetiracetam.
AB - BACKGROUND: Delayed elimination of methotrexate was previously reported in 2
patients receiving concomitant levetiracetam. OBJECTIVE: To explore the potential
interaction between methotrexate and levetiracetam in patients receiving high
dose methotrexate. METHODS: This retrospective study reviewed the records of 81
adults receiving 280 cycles of methotrexate to determine the effects of
levetiracetam on methotrexate elimination. Institutional review board approval
was obtained. RESULTS: Levetiracetam was administered in 33 (12%) cycles of
methotrexate. Patients receiving levetiracetam had significantly lower 24-hour
methotrexate concentrations compared with those not receiving levetiracetam (2.91
vs 7.37 umol/L, P = 0.005). Despite this difference, concentrations at 48 and 72
hours were similar between groups. Times to nontoxic methotrexate concentration
(<0.1 umol/L) were the same regardless of the presence of levetiracetam. The
frequency of delayed elimination at 24, 48, and 72 hours was similar in both
groups as was the frequency of delayed elimination at any time point. Cox
regression demonstrated that levetiracetam was not a significant predictor of
time to nontoxic methotrexate concentration (P = 0.796; HR = 1.058; 95% CI =
0.692-1.617), and logistic regression demonstrated that levetiracetam was not a
significant predictor of delayed elimination at any time point. Levetiracetam use
was similar between groups when comparing patients experiencing delayed
elimination at any time point with those without delayed elimination (13% vs 10%,
respectively, P = 0.527). CONCLUSION: This study does not support the previous
reports of a significant interaction between levetiracetam and methotrexate. A
clinically significant interaction is unlikely in those without additional risk
factors for delayed elimination.
PMID- 27511815
TI - EAN guidelines on central neurostimulation therapy in chronic pain conditions.
AB - BACKGROUND AND PURPOSE: Our aim was to update previous European Federation of
Neurological Societies guidelines on neurostimulation for neuropathic pain,
expanding the search to new techniques and to chronic pain conditions other than
neuropathic pain, and assessing the evidence with the Grading of Recommendations,
Assessment, Development and Evaluation (GRADE) system. METHODS: A systematic
review and meta-analysis of trials published between 2006 and December 2014 was
conducted. Pain conditions included neuropathic pain, fibromyalgia, complex
regional pain syndrome (CRPS) type I and post-surgical chronic back and leg pain
(CBLP). Spinal cord stimulation (SCS), deep brain stimulation (DBS), epidural
motor cortex stimulation (MCS), repetitive transcranial magnetic stimulation
(rTMS) and transcranial direct electrical stimulation (tDCS) of the primary motor
cortex (M1) or dorsolateral prefrontal cortex (DLPFC) were assessed. The GRADE
system was used to assess quality of evidence and propose recommendations.
RESULTS: The following recommendations were reached: 'weak' for SCS added to
conventional medical management in diabetic painful neuropathy, CBLP and CRPS,
for SCS versus reoperation in CBLP, for MCS in neuropathic pain, for rTMS of M1
in neuropathic pain and fibromyalgia and for tDCS of M1 in neuropathic pain;
'inconclusive' for DBS in neuropathic pain, rTMS and tDCS of the DLPFC, and for
motor cortex tDCS in fibromyalgia and spinal cord injury pain. CONCLUSIONS: Given
the poor to moderate quality of evidence identified by this review, future large
scale multicentre studies of non-invasive and invasive neurostimulation are
encouraged. The collection of higher quality evidence of the predictive factors
for the efficacy of these techniques, such as the duration, quality and severity
of pain, is also recommended.
PMID- 27511816
TI - The insidious appearance of the dissecting aneurysm: Imaging findings and related
pathophysiology. A report of two cases.
AB - Intracranial dissecting aneurysms have been frequently reported to present with
fairly challenging and time-variable imaging findings that can be mostly
explained by the pathological mechanisms that underline the dissection. We
present two cases of spontaneous dissecting aneurysm of the supraclinoid ICA,
both clinically presenting with SAH, but characterized by different progression
of clinical symptoms and imaging. However, in both cases an outpouch and a mild
fusiform dilation of the supraclinoid ICA was present in the initial CTA
performed after the occurrence of symptoms. These findings were well depicted by
the MPR reformats performed retrospectively. We postulate that this finding may
represent the point of initial transmural dissection and we recommend that
careful analysis of the CTA MRP reformatted images should be performed in order
to detect this finding promptly.
PMID- 27511818
TI - Early angiographic changes of intra-aneurysmal flow after flow-diverter stent
treatment are not predictive of therapeutic success.
AB - BACKGROUND AND PURPOSE: Flow-diverter stents (FDS) are new devices for the
endovascular treatment of intracranial aneurysms (IAs) promoting progressive
aneurysmal thrombosis. To date, the delay of aneurysmal exclusion remains
unclear. We evaluated the correlation between angiographic changes in the first
24 hours and 12-month occlusion in aneurysms treated with FDS. METHODS: We
retrospectively analyzed the intra-aneurysmal flow by evaluating the in-flow and
out-flow delays on preoperative, immediate postoperative, 24-hour and 12-month
follow-up angiography. Dichotomy of in-flow and out-flow within the aneurysm was
considered as the time of contrast filling and time of contrast washing
relatively to the parent artery. The delay times were compared and correlated
with the therapeutic success of FDS at 12 months of follow-up. RESULTS: Out of 14
treated IAs, in 13 consecutive patients, n = 10 (71%) aneurysms showed complete
occlusion at 12 months. Between immediate postoperative and 24-hour control, 10
aneurysms (71%) demonstrated in-flow modification, with eight increasing, two
decreasing and four having no change. There were no statistical differences in
therapeutic success in relation to the different flow-related profiles of intra
aneurysmal flux.Out-flow modifications were found in 11 aneurysms (79%) between
immediate postoperative and 24-hour control, with five increasing, six decreasing
and three having no change. Similar to the in-flow changes, there were no
statistical differences in therapeutic success relative to the flow-related
profiles. CONCLUSIONS: Early angiographic changes after FDS placement are very
frequent, but are not correlated with the 12-month technical success of flow
diversion techniques.
PMID- 27511819
TI - Significant Improvement of Antithrombotic Responses to Clopidogrel by Use of a
Novel Conjugate as Revealed in an Arterial Model of Thrombosis.
AB - Clopidogrel is a prodrug that requires bioactivation by cytochrome P450 (P450)
enzymes to a pharmacologically active metabolite for antiplatelet action. The
clinical limitations of clopidogrel are in large part due to its poor
pharmacokinetics resulting from inefficient bioactivation by P450s. In this
study, we determined the pharmacokinetics and pharmacodynamics of a novel
conjugate of clopidogrel, referred to as ClopNPT, in animal models and we
evaluated its potential to overcome the limitations of clopidogrel. Results from
pharmacokinetic (PK) studies showed that ClopNPT released the active metabolite
with a time to maximal plasma concentration of <5 minutes in C57BL/6 mice after
either oral or intravenous administration, and plasma concentrations of the
active metabolite reached Cmax values of 1242 and 1100 ng/ml after a 10-mg/kg
oral dose and a 5-mg/kg intravenous dose, respectively. Furthermore, ClopNPT was
highly effective in preventing arterial thrombosis in rabbits and mice after
vascular injuries. Formation of occlusive thrombi was prevented by ClopNPT at the
1-mg/kg dose with no significant increase in tongue bleeding time, whereas
clopidogrel was ineffective at the same dose. These results suggest that ClopNPT
has favorable PK/pharmacodynamic properties that can potentially overcome the
attenuated PK properties of clopidogrel and thus significantly improve the
efficacy of antiplatelet therapy.
PMID- 27511817
TI - Neurovascular manifestations of connective-tissue diseases: A review.
AB - Patients with connective tissue diseases are thought to be at a higher risk for a
number of cerebrovascular diseases such as intracranial aneurysms, dissections,
and acute ischemic strokes. In this report, we aim to understand the prevalence
and occurrences of such neurovascular manifestations in four heritable connective
tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type
1, and Loeys-Dietz syndrome. We discuss the fact that although there are various
case studies reporting neurovascular findings in these connective tissue
diseases, there is a general lack of case-control and prospective studies
investigating the true prevalence of these findings in these patient populations.
Furthermore, the differences observed in the manifestations and histology of such
disease pathologies encourages future multi-center registries and studies in
better characterizing the pathophysiology, prevalence, and ideal treatment
options of neurovascular lesions in patents with connective tissue diseases.
PMID- 27511821
TI - Case of immunoglobulin G4-related disease with unusual cutaneous manifestation.
PMID- 27511822
TI - Dislocation network with pair-coupling structure in {111} gamma/gamma' interface
of Ni-based single crystal superalloy.
AB - The gamma/gamma' interface dislocation network is reported to improve the high
temperature creep resistance of single crystal superalloys and is usually found
to deposit in {001} interface. In this work, a new type of dislocation network
was found in {111} gamma/gamma' interface at a single crystal model superalloy
crept at 1100 degrees C/100 MPa. The dislocations in the network are screw with
Burgers vectors of 1/2 a<110> and most interestingly, they exhibit a pair
coupling structure. Further investigation indicates that the formation of {111}
interface dislocation network occurs when the gamma' raft structure begins to
degrade by the dislocations cutting into the rafted gamma' through the interface.
In this condition, the pair-coupling structure is established by the dislocations
gliding in a single {111} plane of gamma', in order to remove the anti-phase
boundary in gamma'; these dislocations also act as diffusion channels for
dissolving of the gamma' particle that is unstable under the interfacial stress
from lattice misfit, which leads to the formation of {111}-type zigzag interface.
The formation of this network arises as a consequence of more negative misfit,
low-alloying gamma' particle and proper test conditions of temperature and
stress.
PMID- 27511823
TI - The role of FDG-PET in localization of recurrent lesions of differentiated
thyroid cancer (DTC) in patients with asymptomatic hyperthyroglobulinemia in a
real clinical practice.
AB - INTRODUCTION: Available methods, including serum thyroglobulin (Tg) measurement
and whole-body scan (WBS) performed after radioiodine administration, allow for a
precise diagnostics in differentiated thyroid cancer (DTC). However, some
asymptomatic patients demonstrate negative WBS despite a high Tg serum
concentration. In these subjects, fluorodeoxyglucose-positron emission tomography
(FDG-PET) should be considered. The primary aim of our study was to evaluate a
diagnostic value of FDG-PET in asymptomatic hyperthyroglobulinemia. The secondary
one was to determine a prognostic value of a negative FDG-PET result in DTC
patients with elevated Tg level. MATERIAL: One hundred and ten FDG-PET/CT scans
were retrospectively analyzed, 85 scans were done under TSH stimulation and 25 on
LT4 suppressive therapy. Follow-up ranged between 4 and 9 years. RESULTS: The
first FDG-PET/CT detected cancer foci in 49 subjects with a global sensitivity of
45%. When the sensitivity was evaluated with reference to TSH stimulation and
suppression, its values were 50 and 28% respectively. In 42 patients, FDG-PET
failed to diagnose the reason for elevated Tg level. During further follow-up, in
17 of them, DTC recurrence was detected by other methods (CT, MRI, US). Fourteen
subjects with asymptomatic hyperthyroglobulinemia were free of DTC progression
for at least 4 years. CONCLUSIONS: FDG-PET in DTC patients with asymptomatic
hyperthyroglobulinemia constitutes a valuable diagnostic tool. Negative FDG-PET
demonstrated a limited prognostic significance, as only every third patient did
not show DTC progression. Moreover, negative FDG-PET does not justify less strict
DTC monitoring, because it is related to 40% risk of relapse during the 5-year
follow-up.
PMID- 27511820
TI - Target Organ Metabolism, Toxicity, and Mechanisms of Trichloroethylene and
Perchloroethylene: Key Similarities, Differences, and Data Gaps.
AB - Trichloroethylene (TCE) and perchloroethylene or tetrachloroethylene (PCE) are
high-production volume chemicals with numerous industrial applications. As a
consequence of their widespread use, these chemicals are ubiquitous environmental
contaminants to which the general population is commonly exposed. It is widely
assumed that TCE and PCE are toxicologically similar; both are simple olefins
with three (TCE) or four (PCE) chlorines. Nonetheless, despite decades of
research on the adverse health effects of TCE or PCE, few studies have directly
compared these two toxicants. Although the metabolic pathways are qualitatively
similar, quantitative differences in the flux and yield of metabolites exist.
Recent human health assessments have uncovered some overlap in target organs that
are affected by exposure to TCE or PCE, and divergent species- and sex
specificity with regard to cancer and noncancer hazards. The objective of this
minireview is to highlight key similarities, differences, and data gaps in target
organ metabolism and mechanism of toxicity. The main anticipated outcome of this
review is to encourage research to 1) directly compare the responses to TCE and
PCE using more sensitive biochemical techniques and robust statistical
comparisons; 2) more closely examine interindividual variability in the
relationship between toxicokinetics and toxicodynamics for TCE and PCE; 3)
elucidate the effect of coexposure to these two toxicants; and 4) explore new
mechanisms for target organ toxicity associated with TCE and/or PCE exposure.
PMID- 27511824
TI - Hypothyroidism incidence in and around pregnancy: a Danish nationwide study.
AB - OBJECTIVE: Immunological changes in and after a pregnancy may influence the onset
of autoimmune diseases. An increased incidence of hyperthyroidism has been
observed both in early pregnancy and postpartum, but it remains to be studied if
the incidence of hypothyroidism varies in a similar way. DESIGN: Population-based
cohort study using Danish nationwide registers. METHOD: All women who gave birth
to a singleton live-born child in Denmark from 1999 to 2008 (n = 403 958) were
identified, and data on hospital diagnosis of hypothyroidism and redeemed
prescriptions of thyroid hormone were extracted. The overall incidence rate (IR)
of hypothyroidism during 1997-2010 and the IR in three-month intervals before,
during and after the woman's first pregnancy in the study period were calculated
and compared with the IR of hyperthyroidism. RESULTS: Altogether 5220 women were
identified with onset of hypothyroidism from 1997 to 2010 (overall IR 92.3/100
000/year) and 1572 women developed hypothyroidism in the period from 2 years
before to 2 years after birth of the first child in the study period. The
incidence of hypothyroidism decreased during the pregnancy (incidence rate ratio
(IRR) vs overall IR in the rest of the study period: first trimester: 0.89 (95%
CI: 0.66-1.19), second trimester: 0.71 (0.52-0.97), third trimester: 0.29 (0.19
0.45)) and increased after birth with the highest level at 4-6 months postpartum
(IRR 3.62 (2.85-4.60)). CONCLUSION: These are the first population-based data on
the incidence of hypothyroidism in and around pregnancy. The incidence declined
during pregnancy followed by a sharp increase postpartum. Notably, hypothyroidism
as opposed to hyperthyroidism showed no early pregnancy increase.
PMID- 27511826
TI - Congenital hypothyroidism with delayed TSH elevation in low-birth-weight infants:
incidence, diagnosis and management.
AB - OBJECTIVE: To evaluate the incidence of congenital hypothyroidism (CH) with
delayed TSH elevation among low-birth-weight (LBW) newborns in North-Eastern
Italy and to verify if they need a second or third screening. DESIGN: Analysis of
clinical and biochemical data of newborns affected by CH with delayed TSH
elevation identified by neonatal screening. METHODS: Data of all newborns with
birth weight (BW) <2500 g and evidence of delayed TSH elevation at newborn
screening were collected between 2011 and 2014. Confirmatory tests were based on
serum TSH and FT4 levels. All their clinical signs at diagnosis were reported.
RESULTS: 57.5% of LBW newborns with delayed TSH increase at neonatal screening
presented a CH with delayed TSH elevation and began a treatment with l-thyroxine.
The incidence of this condition in North-Eastern Italy is therefore 1:908. The
remaining infants presented a subclinical hypothyroidism (21.25%) or a complete
normal serum thyroid function (21.25%). These data could be drawn only from a
retesting strategy of neonatal screening. CONCLUSIONS: Our report describes the
incidence of CH with delayed TSH rise in North-Eastern Italy and differentiates
this clinical condition from other thyroid dysfunctions of preterm or LBW
newborns. The second-screening strategy for CH in neonates with BW < 2500 g
proved useful in detecting newborns who otherwise would not be identified at the
first screening.
PMID- 27511825
TI - The link between metabolic features and TSH levels in polycystic ovary syndrome
is modulated by the body weight: an euglycaemic-hyperinsulinaemic clamp study.
AB - OBJECTIVE: To evaluate the link among thyroid function, glucose/insulin
metabolism and steroid hormones in women with polycystic ovary syndrome (PCOS),
and to verify if the body mass index (BMI) might influence the interplay between
PCOS features and subclinical hypothyroidism (SCH). STUDY DESIGN: Case-control
study conducted from January to December 2014. METHODS: One-hundred fifty-four
young women with PCOS, according to Rotterdam criteria, and 88 controls were
enrolled in an academic research environment. Anthropometric evaluation, hormonal
and lipid assays, oral glucose tolerance test (OGTT) and euglycaemic
hyperinsulinaemic clamp were performed. Hirsutism was assessed with the Ferriman
Gallwey (FG) score. MAIN RESULTS: SCH was found in 14% of PCOS subjects and in 1%
of controls (P < 0.01). In PCOS women, TSH levels were directly correlated with
fasting glycaemia, but not with other hormonal and metabolic parameters. When
PCOS patients were classified on the basis of BMI, TSH levels significantly
correlated with insulin secretion, insulin resistance, DHEAS and cortisol levels
in obese PCOS women. Inverse correlations were found between TSH and both
oestradiol and SHBG in the same group. In nonobese PCOS patients, only waist-to
hip ratio values were correlated with TSH. The prevalence of SCH was not
different between nonobese and obese PCOS groups (14 and 15% respectively).
However, SCH was associated with higher levels of insulin, DHEAS, cortisol and FG
score only in the obese subgroup. CONCLUSIONS: Our data confirm that the
prevalence of SCH is increased in PCOS women. The presence of SCH is associated
with endocrine and metabolic imbalances of PCOS, and the excessive body weight
seems to promote this interplay.
PMID- 27511827
TI - Performance comparison of MOF and other sorbent materials in removing key
odorants emitted from pigpen slurry.
AB - A batch-type dynamic headspace (HS) system was used to generate vapor-phase
volatile organic compounds (VOCs) from a pigpen slurry sample. Sorptive removal
capability of MOF-199 and other sorbents (zeolite (ZL) and activated carbon (AC))
was assessed against a total of 13 slurry-borne odorants ((methyl ethyl ketone
(MEK), isobutyl alcohol (i-BuAl), benzene (B), toluene (T), p-xylene (p-X), m
xylene (m-X), o-xylene (o-X), styrene (S), o-cresol (o-C), phenol (PhAl), p
cresol (p-C), indole (ID), and skatole (SK)). Adsorption capacity of MOF-199 and
two sorbents, when assessed for the 13 odorants at a 10% breakthrough volume
(BTV), was 22.6 +/- 42.3, 0.70 +/- 1.08, and 11.0 +/- 18.3 MUg g(-1),
respectively. The adsorption capacity (MUg g(-1)) assessed at 10% BTV showed the
superiority of MOF-199 towards phenolic and indolic compounds (such as o-C (0.31
+/- 0.04), PhAl (61.6 +/- 4.98), p-C (140 +/- 7.95), ID (27.8 +/- 2.23),
and SK (63.9 +/- 1.55)), demonstrating the feasibility of MOF as sorption media
for treating certain nuisance components.
PMID- 27511828
TI - Sustainability assessment of electrokinetic bioremediation compared with
alternative remediation options for a petroleum release site.
AB - Sustainable management practices can be applied to the remediation of
contaminated land to maximise the economic, environmental and social benefits of
the process. The Sustainable Remediation Forum UK (SuRF-UK) have developed a
framework to support the implementation of sustainable practices within
contaminated land management and decision making. This study applies the
framework, including qualitative (Tier 1) and semi-quantitative (Tier 2)
sustainability assessments, to a complex site where the principal contaminant
source is unleaded gasoline, giving rise to a dissolved phase BTEX and MTBE
plume. The pathway is groundwater migration through a chalk aquifer and the
receptor is a water supply borehole. A hydraulic containment system (HCS) has
been installed to manage the MTBE plume migration. The options considered to
remediate the MTBE source include monitored natural attenuation (MNA), air
sparging/soil vapour extraction (AS/SVE), pump and treat (PT) and electrokinetic
enhanced bioremediation (EK-BIO). A sustainability indictor set from the SuRF-UK
framework, including priority indicator categories selected during a stakeholder
engagement workshop, was used to frame the assessments. At Tier 1 the options are
ranked based on qualitative supporting information, whereas in Tier 2 a multi
criteria analysis is applied. Furthermore, the multi-criteria analysis was
refined for scenarios where photovoltaics (PVs) are included and amendments are
excluded from the EK-BIO option. Overall, the analysis identified AS/SVE and EK
BIO as more sustainable remediation options at this site than either PT or MNA.
The wider implications of this study include: (1) an appraisal of the management
decision from each Tier of the assessment with the aim to highlight areas for
time and cost savings for similar assessments in the future; (2) the observation
that EK-BIO performed well against key indicator categories compared to the other
intensive treatments; and (3) introducing methods to improve the sustainability
of the EK-BIO treatment design (such as PVs) did not have a significant effect in
this instance.
PMID- 27511829
TI - The Effectiveness Of Social Media (Facebook) Compared With More Traditional
Advertising Methods for Recruiting Eligible Participants To Health Research
Studies: A Randomized, Controlled Clinical Trial.
AB - BACKGROUND: Recruiting participants for research studies can be difficult and
costly. The popularity of social media platforms (eg, Facebook) has seen
corresponding growth in the number of researchers turning to social networking
sites and their embedded advertising frameworks to locate eligible participants
for studies. Compared with traditional recruitment strategies such as print
media, social media advertising has been shown to be favorable in terms of its
reach (especially with hard-to-reach populations), cost effectiveness, and
usability. However, to date, no studies have examined how participants recruited
via social media progress through a study compared with those recruited using
more traditional recruitment strategies. OBJECTIVES: (1) Examine whether visiting
the study website prior to being contacted by researchers creates self-screened
participants who are more likely to progress through all study phases (eligible,
enrolled, completed); (2) compare conversion percentages and cost effectiveness
of each recruitment method at each study phase; and, (3) compare demographic and
smoking characteristics of participants recruited through each strategy to
determine if they attract similar samples. METHODS: Participants recruited to a
smoking cessation clinical trial were grouped by how they had become aware of the
study: via social media (Facebook) or traditional media (eg, newspaper, flyers,
radio, word of mouth). Groups were compared based on throughput data (conversion
percentages and cost) as well as demographic and smoking characteristics.
RESULTS: Visiting the study website did not result in individuals who were more
likely to be eligible for (P=.24), enroll in (P=.20), or complete (P=.25) the
study. While using social media was more cost effective than traditional methods
when we examined earlier endpoints of the recruitment process (cost to obtain a
screened respondent: AUD $22.73 vs $29.35; cost to obtain an eligible respondent:
$37.56 vs $44.77), it was less cost effective in later endpoints (cost per
enrolled participant: $56.34 vs $52.33; cost per completed participant: $103.66
vs $80.43). Participants recruited via social media were more likely to be
younger (P=.001) and less confident in their quit attempts (P=.004) compared to
those recruited via traditional methods. CONCLUSIONS: Our study suggests that
while social media advertising may be effective in generating interest from
potential participants, this strategy's ability to attract conscientious recruits
is more questionable. Researchers considering using online resources (eg, social
media advertising, matrix codes) should consider including prescreening questions
to promote conversion percentages. Ultimately, researchers seeking to maximize
their recruitment budget should consider using a combination of advertising
strategies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
ACTRN 12614000329662;
https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365947l
(Archived by WebCite at http://www.webcitation.org/6jc6zXWZI).
PMID- 27511830
TI - Healthcare Professionals' Preferences and Perceived Barriers for Routine
Assessment of Patient-Reported Outcomes in Pediatric Oncology Practice: Moving
Toward International Processes of Change.
AB - BACKGROUND: Using patient-reported outcomes (PROs) in clinical practice has been
shown to enhance detection of health-related quality of life problems and
satisfaction with care in children with cancer. This study seeks to identify
which PRO information healthcare professionals (HCPs) find useful and what the
perceived barriers for routinely assessing PROs are. PROCEDURE: A total of 352
pediatric HCPs (43% male) from 52 countries completed a semistructured online 28
item questionnaire. Descriptive statistics (percentages) were used to identify
highly important PRO information and perceived barriers. HCPs' perceived barriers
were compared according to gender, years of work experience, and country using a
Fishers exact test. RESULTS: The five highest ranked PRO topics relevant in
routine assessment by HCPs were as follows: pain (98%), feeling sad or depressed
(96%), overall physical symptoms (95%), problems with therapy adherence (94%),
and overall emotional issues (93%). Five lowest ranked topics were as follows:
difficulties praying (50%), other spiritual concerns (55, 56, and 60%), and
feeling bored (60%). Barriers for assessing PROs included: time (58%),
insufficient staff (49%), logistics (32%), and financial resources (26%).
Providers from developing countries more often reported barriers concerning
insufficient staff, logistics, and financial resources. CONCLUSIONS: HCPs
strongly value the use of physical and psychosocial PROs within pediatric
oncology practice, but mainly perceive organizational barriers for routine
assessment. To successfully integrate PROs, efforts should be made to address HCP
perceived barriers, such that patient-reported problems can be detected and
timely referrals made.
PMID- 27511831
TI - Fibroproliferative response to urothelial failure obliterates the ureter lumen in
a mouse model of prenatal congenital obstructive nephropathy.
AB - Congenital obstructive nephropathy (CON) is the most prevalent cause of pediatric
chronic kidney disease and end-stage renal disease. The ureteropelvic junction
(UPJ) region, where the renal pelvis transitions to the ureter, is the most
commonly obstructed site in CON. The underlying causes of congenital UPJ
obstructions remain poorly understood, especially when they occur in utero, in
part due to the lack of genetic animal models. We previously showed that
conditional inactivation of Sec10, a central subunit of the exocyst complex, in
the epithelial cells of the ureter and renal collecting system resulted in late
gestational bilateral UPJ obstructions with neonatal anuria and death. In this
study, we show that without Sec10, the urothelial progenitor cells that line the
ureter fail to differentiate into superficial cells, which are responsible for
producing uroplakin plaques on the luminal surface. These Sec10-knockout
urothelial cells undergo cell death by E17.5 and the urothelial barrier becomes
leaky to luminal fluid. Also at E17.5, we measured increased expression of
TGFbeta1 and genes associated with myofibroblast activation, with evidence of
stromal remodeling. Our findings support the model that a defective urothelial
barrier allows urine to induce a fibrotic wound healing mechanism, which may
contribute to human prenatal UPJ obstructions.
PMID- 27511832
TI - The protein inventory of Clostridium difficile grown in complex and minimal
medium.
AB - The intestinal pathogen Clostridium difficile is causing an increasing number of
infections often characterized by severity and high relapse rates. Profound
knowledge of the physiology of the pathogen could help to develop new treatment
strategies. Proteomics, a valuable tool to study bacterial physiology, was used
in this work to establish a benchmark proteome of reference strain C. difficile
630Deltaerm with MS-based details on all identified proteins. Our elaborate
annotation and visualization of C. difficile 630Deltaerm 3764 ORFs will serve as
a valuable base for researchers having to evaluate global expression studies. To
exemplify expression variability, protein expression of late exponentially
growing cells in complex brain-heart infusion medium and C. difficile minimal
medium was compared. Noteworthy results of this comparison are as follows: (i)
the higher expression of enzymes for the biosynthesis of some vitamins and purine
and (ii) downregulation of proteins involved in butanoate fermentation in C.
difficile minimal medium. However, the abundance of proteins involved in DNA
metabolism, protein synthesis, and the cell envelope showed no variation between
the two growth media.
PMID- 27511833
TI - Prognostic implications of 2005 Gleason grade modification. Population-based
study of biochemical recurrence following radical prostatectomy.
AB - OBJECTIVE: To assess the impact of the 2005 modification of the Gleason
classification on risk of biochemical recurrence (BCR) after radical
prostatectomy (RP). PATIENTS AND METHODS: In the Prostate Cancer data Base Sweden
(PCBaSe), 2,574 men assessed with the original Gleason classification and 1,890
men assessed with the modified Gleason classification, diagnosed between 2003 and
2007, underwent primary RP. Histopathology was reported according to the Gleason
Grading Groups (GGG): GGG1 = Gleason score (GS) 6, GGG2 = GS 7(3 + 4), GGG3 = GS
7(4 + 3), GGG4 = GS 8 and GGG5 = GS 9-10. Cumulative incidence and multivariable
Cox proportional hazards regression models were used to assess difference in BCR.
RESULTS: The cumulative incidence of BCR was lower using the modified compared to
the original classification: GGG2 (16% vs. 23%), GGG3 (21% vs. 35%) and GGG4 (18%
vs. 34%), respectively. Risk of BCR was lower for modified versus original
classification, GGG2 Hazard ratio (HR) 0.66, (95%CI 0.49-0.88), GGG3 HR 0.57
(95%CI 0.38-0.88) and GGG4 HR 0.53 (95%CI 0.29-0.94). CONCLUSION: Due to grade
migration following the 2005 Gleason modification, outcome after RP are more
favourable. Consequently, outcomes from historical studies cannot directly be
applied to a contemporary setting. J. Surg. Oncol. 2016;114:664-670. (c) 2016
Wiley Periodicals, Inc.
PMID- 27511834
TI - Transgenic overexpression of VEGF-C induces weight gain and insulin resistance in
mice.
AB - Obesity comprises great risks for human health, contributing to the development
of other diseases such as metabolic syndrome, type 2 diabetes and cardiovascular
disease. Previously, obese patients were found to have elevated serum levels of
VEGF-C, which correlated with worsening of lipid parameters. We recently
identified that neutralization of VEGF-C and -D in the subcutaneous adipose
tissue during the development of obesity improves metabolic parameters and
insulin sensitivity in mice. To test the hypothesis that VEGF-C plays a role in
the promotion of the metabolic disease, we used K14-VEGF-C mice that overexpress
human VEGF-C under control of the keratin-14 promoter in the skin and monitored
metabolic parameters over time. K14-VEGF-C mice had high levels of VEGF-C in the
subcutaneous adipose tissue and gained more weight than wildtype littermates,
became insulin resistant and had increased ectopic lipid accumulation at 20 weeks
of age on regular mouse chow. The metabolic differences persisted under high-fat
diet induced obesity. These results indicate that elevated VEGF-C levels
contribute to metabolic deterioration and the development of insulin resistance,
and that blockade of VEGF-C in obesity represents a suitable approach to
alleviate the development of insulin resistance.
PMID- 27511835
TI - Do pharmacist-led medication reviews in hospitals help reduce hospital
readmissions? A systematic review and meta-analysis.
AB - AIMS: The aim of this meta-analysis is to examine the impact of in-hospital
pharmacist-led medication reviews in paediatric and adult patients. METHODS:
Relevant studies were identified from the Medline and Cochrane Library databases.
Studies were included if they met the following criteria (without any language or
date restrictions): design: randomized controlled trial; intervention: in
hospital pharmacist-led medication review (experimental group) vs. usual care
(control group); participants: paediatric or adult population. The primary
outcome was all-cause readmissions and/or emergency department (ED) visits at
different time points. The secondary outcomes were all-cause readmissions, all
cause ED visits, drug-related readmissions, mortality, length of hospital stay,
adherence and quality of life. We calculated the relative risk (RR) or mean
differences (MD) with 95% confidence intervals (CIs) for each study. We used
fixed and/or random effects models. Heterogeneity was assessed using the I2
statistic. RESULTS: We systematically reviewed 19 randomized controlled trials
(4805 participants). The readmission rates did not differ between the
experimental group and the control group (RR = 0.97, 95% CI 0.89; 1.05, p =
0.470). The secondary outcomes did not differ between the two groups, except for
in drug-related readmissions, which were lower in the experimental group (RR =
0.25, 95% CI 0.14; 0.45, p < 0.001), and all-cause ED visits (RR = 0.70, 95% CI
0.59; 0.85 p = 0.001). CONCLUSION: The low-quality evidence in this analysis
suggests an impact of pharmacist-led medication reviews on drug-related
readmissions and all-cause ED visits. Few studies reported on adherence and
quality of life. More high-quality randomized clinical trials are needed to
assess the impact of pharmacist-led medication reviews on patient-relevant
outcomes, including adherence and quality of life.
PMID- 27511836
TI - Population Pharmacokinetic and Pharmacodynamic Modeling Analysis of GCC-4401C, a
Novel Direct Factor Xa Inhibitor, in Healthy Volunteers.
AB - GCC-4401C, an orally active direct factor Xa inhibitor that is similar to
rivaroxaban, is currently under development for venous thromboembolic disease
(VTE). The purpose of this study was to characterize the pharmacokinetics (PKs)
and pharmacodynamics (PDs) of GCC-4401C by population modeling analysis and to
predict proper dosage regimens compared to rivaroxaban using data from two phase
I clinical studies. Plasma GCC-4401C concentrations over time were best described
by a two-compartment linear model and body weight was associated with central
volume of distribution. Relevant PD markers generally changed in a dose-dependent
manner and were described well with sigmoid, simple maximum effect, or linear
models. GCC-4401C was absorbed more rapidly than rivaroxaban. Comparisons based
on simulations of PD marker changes over time suggest that 20 mg and 40 mg of GCC
4401C administered under fasted status are comparable to 10 mg and 20 mg of
rivaroxaban under fed status.
PMID- 27511837
TI - Control of sensory neuron excitability by serotonin involves 5HT2C receptors and
Ca(2+)-activated chloride channels.
AB - Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that
sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling
mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by
5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons
dissociated from rat DRGs were used to investigate effects of 5HT on membrane
excitability and currents through ligand- as well as voltage-gated ion channels.
In 58% of the neurons tested, 5HT increased action potential firing, an effect
that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the
5HT3 antagonist tropisetron. Unlike other algogenic mediators, such as PGE2 and
bradykinin, 5HT did not affect currents through TTX-resistant Na(+) channels or
Kv7 K(+) channels. In all neurons investigated, 5HT potentiated capsaicin-evoked
currents through TRPV1 channels, an effect that was attenuated by antagonists at
5HT2A (4 F 4 PP), 5HT2B (SB 204741), as well as 5HT2C (RS 102221) receptors. 5HT
triggered slowly arising inward Cl(-) currents in 53% of the neurons. This effect
was antagonized by the 5HT2C receptor blocker only, and the current was prevented
by an inhibitor of Ca(2+)-activated chloride channels (CaCC). The 5HT-induced
increase in action potential firing was also abolished by this CaCC blocker and
by the TRPV1 inhibitor capsazepine. Amongst the subtype selective 5HT2
antagonists, only RS 102221 (5HT2C-selectively) counteracted the rise in action
potential firing elicited by 5HT. These results show that 5HT excites DRG neurons
mainly via 5HT2C receptors which concomitantly mediate a sensitization of TRPV1
channels and an opening of CaCCs.
PMID- 27511839
TI - Acute stimulation of brain mu opioid receptors inhibits glucose-stimulated
insulin secretion via sympathetic innervation.
AB - Pancreatic insulin-secreting beta-cells express opioid receptors, whose
activation by opioid peptides modulates hormone secretion. Opioid receptors are
also expressed in multiple brain regions including the hypothalamus, where they
play a role in feeding behavior and energy homeostasis, but their potential role
in central regulation of glucose metabolism is unknown. Here, we investigate
whether central opioid receptors participate in the regulation of insulin
secretion and glucose homeostasis in vivo. C57BL/6J mice were acutely treated by
intracerebroventricular (i.c.v.) injection with specific agonists for the three
main opioid receptors, kappa (KOR), delta (DOR) and mu (MOR) opioid receptors:
activation of KOR and DOR did not alter glucose tolerance, whereas activation of
brain MOR with the specific agonist DAMGO blunted glucose-stimulated insulin
secretion (GSIS), reduced insulin sensitivity, increased the expression of
gluconeogenic genes in the liver and, consequently, impaired glucose tolerance.
Pharmacological blockade of alpha2A-adrenergic receptors prevented DAMGO-induced
glucose intolerance and gluconeogenesis. Accordingly, DAMGO failed to inhibit
GSIS and to impair glucose tolerance in alpha2A-adrenoceptor knockout mice,
indicating that the effects of central MOR activation on beta-cells are mediated
via sympathetic innervation. Our results show for the first time a new role of
the central opioid system, specifically the MOR, in the regulation of insulin
secretion and glucose metabolism.
PMID- 27511840
TI - Progress in Vulvar and Endometrial Cancers: Exploiting Anatomy and Biology and
Improving Systemic Therapy.
PMID- 27511838
TI - The kynurenine pathway and the brain: Challenges, controversies and promises.
AB - Research on the neurobiology of the kynurenine pathway has suffered years of
relative obscurity because tryptophan degradation, and its involvement in both
physiology and major brain diseases, was viewed almost exclusively through the
lens of the well-established metabolite serotonin. With increasing recognition
that kynurenine and its metabolites can affect and even control a variety of
classic neurotransmitter systems directly and indirectly, interest is expanding
rapidly. Moreover, kynurenine pathway metabolism itself is modulated in
conditions such as infection and stress, which are known to induce major changes
in well-being and behaviour, so that kynurenines may be instrumental in the
etiology of psychiatric and neurological disorders. It is therefore likely that
the near future will not only witness the discovery of additional physiological
and pathological roles for brain kynurenines, but also ever-increasing interest
in drug development based on these roles. In particular, targeting the kynurenine
pathway with new specific agents may make it possible to prevent disease by
appropriate pharmacological or genetic manipulations. The following overview
focuses on areas of kynurenine research which are either controversial, of major
potential therapeutic interest, or just beginning to receive the degree of
attention which will clarify their relevance to neurobiology and medicine. It
also highlights technical issues so that investigators entering the field, and
new research initiatives, are not misdirected by inappropriate experimental
approaches or incorrect interpretations at this time of skyrocketing interest in
the subject matter. This article is part of the Special Issue entitled 'The
Kynurenine Pathway in Health and Disease'.
PMID- 27511841
TI - Mathematical Optimization of Treatment Schedules.
PMID- 27511843
TI - The Challenges of Treatment Adaptation and De-intensification in Human
Papillomavirus-Positive Oropharyngeal Cancer: The Difficult Journey Back.
PMID- 27511842
TI - Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide
Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally
Advanced Human Papillomavirus-Related Oropharyngeal Carcinoma.
AB - PURPOSE: To report a small substudy of an ongoing large, multi-arm study using
functional imaging to assess pre-/intratreatment hypoxia for all head and neck
cancer, in which we hypothesized that pre- and early-treatment hypoxia assessment
using functional positron emission tomography (PET) imaging may help select which
human papillomavirus (HPV)-positive (HPV(+)) oropharyngeal cancer (OPC) patients
can safely receive radiation de-escalation without jeopardizing treatment
outcomes. METHODS AND MATERIALS: Patients with HPV(+) oropharyngeal carcinoma
were enrolled on an institutional review board-approved prospective study of
which de-escalation based on imaging response was done for node(s) only.
Pretreatment (18)F-fluorodeoxyglucose and dynamic (18)F-FMISO
(fluoromisonidazole) positron emission tomography (PET) scans were performed. For
patients with pretreatment hypoxia on(18)F-FMISO PET (defined as a >1.2 tumor to
muscle standard uptake value ratio), a repeat scan was done 1 week after
chemoradiation. Patients without pretreatment hypoxia or with resolution of
hypoxia on repeat scan received a 10-Gy dose reduction to metastatic lymph
node(s). The 2-year local, regional, distant metastasis-free, and overall
survival rates were estimated using the Kaplan-Meier product-limit method. A
subset of patients had biopsy of a hypoxic node done under image guidance.
RESULTS: Thirty-three HPV(+) OPC patients were enrolled in this pilot study. One
hundred percent showed pretreatment hypoxia (at primary site and/or node[s]), and
among these, 48% resolved (at primary site and/or node[s]); 30% met criteria and
received 10-Gy reduction to the lymph node(s). At the median follow-up of 32
months (range, 21-61 months), the 2-year locoregional control rate was 100%. One
patient failed distantly with persistence of hypoxia on (18)F-FMISO PET. The 2
year distant metastasis-free rate was 97%. The 2-year OS rate was 100%. Hypoxia
on imaging was confirmed pathologically. CONCLUSIONS: Hypoxia is present in
HPV(+) tumors but resolves within 1 week of treatment in 48% of cases either at
the primary site and/or lymph node(s). Our 100% locoregional control rate
suggests that intratreatment functional imaging used to selectively de-escalate
node(s) to 60 Gy was confirmed safe using our stringent imaging criteria.
Intratreatment functional imaging warrants further study to determine its
ultimate role in de-escalation treatment strategies.
PMID- 27511844
TI - Final Results of a Randomized Phase 2 Trial Investigating the Addition of
Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated
Chemoradiation for Locoregionally Advanced Head and Neck Cancer.
AB - PURPOSE: The role of cetuximab in the treatment of locoregionally advanced head
and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2
randomized study, we investigated the addition of cetuximab to both induction
chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. METHODS
AND MATERIALS: Patients with LA-HNSCC were randomized to receive 2 cycles of
weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent
cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy
every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated
radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The
primary endpoint was progression-free survival (PFS), with superiority compared
with historical control achieved if either arm had 2-year PFS >=70%. RESULTS: 110
patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53).
The overall response rate to IC was 91%. Severe toxicity on IC was limited to
rash (23% grade >=3) and myelosuppression (38% grade >=3 neutropenia). The 2-year
rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly
higher than for historical control (P<.001). The 2-year overall survival (OS) was
91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72
months, there were no significant differences in PFS (P=.35) or OS (P=.15)
between the treatment arms. The late outcomes for the entire cohort included 5
year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%,
15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%,
respectively, among human papillomavirus (HPV)-positive patients and 65.9% and
72.5%, respectively, among HPV-negative patients. CONCLUSIONS: The addition of
cetuximab to IC and chemoradiation was tolerable and produced long-term control
of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further
investigation of cetuximab may be warranted in the neoadjuvant setting and with
non-platinum-based chemoradiation.
PMID- 27511845
TI - Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced
Hypothyroidism.
AB - PURPOSE: The incidence of hypothyroidism after radiation therapy for head and
neck cancer (HNC) has been found to be <=53%. Medical treatment of hypothyroidism
can be costly and difficult to titrate. The aim of the present study was to
assess the feasibility of free thyroid transfer as a strategy for the prevention
of radiation-induced damage to the thyroid gland during radiation therapy for
HNC. METHODS AND MATERIALS: A prospective feasibility study was performed
involving 10 patients with a new diagnosis of advanced HNC undergoing ablative
surgery, radial forearm free-tissue transfer reconstruction, and postoperative
adjuvant radiation therapy. During the neck dissection, hemithyroid dissection
was completed with preservation of the thyroid arterial and venous supply for
implantation into the donor forearm site. All patients underwent a diagnostic
thyroid technetium scan 6 weeks and 12 months postoperatively to examine the
functional integrity of the transferred thyroid tissue. RESULTS: Free thyroid
transfer was executed in 9 of the 10 recruited patients with advanced HNC. The
postoperative technetium scans demonstrated strong uptake of technetium at the
forearm donor site at 6 weeks and 12 months for all 9 of the transplanted
patients. CONCLUSIONS: The thyroid gland can be transferred as a microvascular
free transfer with maintenance of function. This technique could represent a
novel strategy for maintenance of thyroid function after head and neck
irradiation.
PMID- 27511846
TI - A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose
Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial.
AB - PURPOSE: Existing intraoperative radiation therapy (IORT) techniques are
criticized for the lack of image guided treatment planning and energy deposition
with, at times, poor resultant dosimetry and low radiation dose. We pioneered a
novel method of IORT that incorporates customized, computed tomography (CT)-based
treatment planning and high-dose-rate (HDR) brachytherapy to overcome these
drawbacks: CT-HDR-IORT. METHODS AND MATERIALS: A phase 1 study was conducted to
demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria
included age >=50 years, invasive or in situ breast cancer, tumor size <3 cm, and
N0 disease. Patients were eligible before or within 30 days of breast-conserving
surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed.
CT images were obtained, a customized HDR brachytherapy plan was created, and a
dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The
catheter was removed, and the skin was closed. The primary endpoints were
feasibility and acute toxicity. Feasibility was defined as IORT treatment
interval (time from CT acquisition until IORT completion) <=90 minutes. The
secondary endpoints included dosimetry, cosmetic outcome, quality of life, and
late toxicity. RESULTS: Twenty-eight patients were enrolled. The 6-month follow
up assessments were completed by 93% of enrollees. The median IORT treatment
interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility
criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%).
There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients
(21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic
outcomes at the last follow-up visit. CONCLUSIONS: CT-HDR-IORT is feasible and
safe. This promising approach for a conformal, image-based, higher-dose breast
IORT is being evaluated in a phase 2 trial.
PMID- 27511847
TI - Cosmesis and Breast-Related Quality of Life Outcomes After Intraoperative
Radiation Therapy for Early Breast Cancer: A Substudy of the TARGIT-A Trial.
AB - PURPOSE: To report the first comprehensive investigation of patient-reported
cosmesis and breast-related quality of life (QOL) outcomes comparing patients
randomized to risk-adapted single-dose intraoperative radiation therapy (TARGIT
IORT) versus external beam radiation therapy (EBRT) on the TARGIT-A trial.
METHODS AND MATERIALS: Longitudinal cosmesis and QOL data were collected from a
subset of TARGIT-A participants who received TARGIT-IORT as a separate procedure
(postpathology). Patients completed a cosmetic assessment before radiation
therapy and annually thereafter for at least 5 years. Patients also completed the
combined European Organization for Research and Treatment of Cancer (EORTC) core
questionnaire and Breast-Specific Module in addition to the Body Image after
Breast Cancer Questionnaire at baseline and annually thereafter. The combined
EORTC questionnaires were also collected 3, 6, and 9 months after wide local
excision. RESULTS: An Excellent-Good cosmetic result was scored more often than a
Fair-Poor result for both treatment groups across all time points. The TARGIT
IORT patients reported better breast-related QOL than EBRT patients.
Statistically and clinically significant differences were seen at month 6 and
year 1, with EBRT patients having moderately worse breast symptoms (a
statistically significant difference of more than 10 in a 100-point scale) than
TARGIT-IORT patients at these time points. CONCLUSION: Patients treated with
TARGIT-IORT on the TARGIT-A trial have similar self-reported cosmetic outcome but
better breast-related QOL outcomes than patients treated with EBRT. This
important evidence can facilitate the treatment decision-making process for
patients who have early breast cancer suitable for breast-conserving surgery and
inform their clinicians.
PMID- 27511850
TI - Quantitative Analysis of (18)F-Fluorodeoxyglucose Positron Emission Tomography
Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic
Cancer Patients Treated With Stereotactic Body Radiation Therapy.
AB - PURPOSE: To identify prognostic biomarkers in pancreatic cancer using high
throughput quantitative image analysis. METHODS AND MATERIALS: In this
institutional review board-approved study, we retrospectively analyzed images and
outcomes for 139 locally advanced pancreatic cancer patients treated with
stereotactic body radiation therapy (SBRT). The overall population was split into
a training cohort (n=90) and a validation cohort (n=49) according to the time of
treatment. We extracted quantitative imaging characteristics from pre-SBRT (18)F
fluorodeoxyglucose positron emission tomography, including statistical,
morphologic, and texture features. A Cox proportional hazard regression model was
built to predict overall survival (OS) in the training cohort using 162 robust
image features. To avoid over-fitting, we applied the elastic net to obtain a
sparse set of image features, whose linear combination constitutes a prognostic
imaging signature. Univariate and multivariate Cox regression analyses were used
to evaluate the association with OS, and concordance index (CI) was used to
evaluate the survival prediction accuracy. RESULTS: The prognostic imaging
signature included 7 features characterizing different tumor phenotypes,
including shape, intensity, and texture. On the validation cohort, univariate
analysis showed that this prognostic signature was significantly associated with
OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging
predictors including tumor volume, maximum standardized uptake value, and total
legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate
analysis, the proposed signature was the only significant prognostic index
(P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical
factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed
signature scored 0.66 and was significantly better than competing prognostic
indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). CONCLUSION: Quantitative
analysis identified novel (18)F-fluorodeoxyglucose positron emission tomography
image features that showed improved prognostic value over conventional imaging
metrics. If validated in large, prospective cohorts, the new prognostic signature
might be used to identify patients for individualized risk-adaptive therapy.
PMID- 27511848
TI - Association of Locoregional Control With High Body Mass Index in Women Undergoing
Breast Conservation Therapy for Early-Stage Breast Cancer.
AB - PURPOSE: Obesity, as measured by the body mass index (BMI), is a risk factor for
distant recurrence and decreased survival in breast cancer. We sought to
determine whether the BMI correlated with local recurrence and reduced survival
in a cohort of predominantly obese women treated with breast conservation
therapy. METHODS AND MATERIALS: From 1998 to 2010, 154 women with early-stage
invasive breast cancer and 39 patients with ductal carcinoma in situ underwent
prone whole breast irradiation. Cox proportional hazards regression, Kaplan-Meier
methods with the log-rank test, and multivariate analysis were used to explore
the association of the outcomes with the BMI. RESULTS: The median patient age was
60 years, and the median follow-up duration was 73 months. The median BMI was
33.2 kg/m(2); 91% of the patients were overweight (BMI >=25 kg/m(2)) and 69% of
the patients were clinically obese (BMI >=30 kg/m(2)). The BMI was significantly
associated with the locoregional recurrence-free interval for patients with
invasive cancer and ductal carcinoma in situ (hazard ratio [HR], 1.09; P=.047).
Also, a trend was seen for increased locoregional recurrence with a higher BMI
(P=.09) for patients with invasive disease, which was significant when examining
the outcomes with a BMI stratified by the median value of 33.2 kg/m(2) (P=.008).
A greater BMI was also significantly associated with decreased distant recurrence
free interval (HR, 1.09; P=.011) and overall survival (HR, 1.09; P=.004); this
association remained on multivariate analysis (distant recurrence-free interval,
P=.034; overall survival, P=.0007). CONCLUSIONS: These data suggest that the BMI
might affect the rate of locoregional recurrence in breast cancer patients. A
higher BMI predicted a worse distant recurrence-free interval and overall
survival. The present investigation adds to the increasing evidence that BMI is
an important prognostic factor in early-stage breast cancer treated with breast
conservation therapy.
PMID- 27511849
TI - Development and Validation of Consensus Contouring Guidelines for Adjuvant
Radiation Therapy for Bladder Cancer After Radical Cystectomy.
AB - PURPOSE: To develop multi-institutional consensus clinical target volumes (CTVs)
and organs at risk (OARs) for male and female bladder cancer patients undergoing
adjuvant radiation therapy (RT) in clinical trials. METHODS AND MATERIALS: We
convened a multidisciplinary group of bladder cancer specialists from 15 centers
and 5 countries. Six radiation oncologists and 7 urologists participated in the
development of the initial contours. The group proposed initial language for the
CTVs and OARs, and each radiation oncologist contoured them on computed
tomography scans of a male and female cystectomy patient with input from >=1
urologist. On the basis of the initial contouring, the group updated its CTV and
OAR descriptions. The cystectomy bed, the area of greatest controversy, was
contoured by another 6 radiation oncologists, and the cystectomy bed contouring
language was again updated. To determine whether the revised language produced
consistent contours, CTVs and OARs were redrawn by 6 additional radiation
oncologists. We evaluated their contours for level of agreement using the Landis
Koch interpretation of the kappa statistic. RESULTS: The group proposed that
patients at elevated risk for local-regional failure with negative margins should
be treated to the pelvic nodes alone (internal/external iliac, distal common
iliac, obturator, and presacral), whereas patients with positive margins should
be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the
rectum, bowel space, bone marrow, and urinary diversion. Consensus language
describing the CTVs and OARs was developed and externally validated. The revised
instructions were found to produce consistent contours. CONCLUSIONS: Consensus
descriptions of CTVs and OARs were successfully developed and can be used in
clinical trials of adjuvant radiation therapy for bladder cancer.
PMID- 27511851
TI - A Voxel-Based Approach to Explore Local Dose Differences Associated With
Radiation-Induced Lung Damage.
AB - PURPOSE: To apply a voxel-based (VB) approach aimed at exploring local dose
differences associated with late radiation-induced lung damage (RILD). METHODS
AND MATERIALS: An interinstitutional database of 98 patients who were Hodgkin
lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic
radiation therapy was analyzed in the study. Eighteen patients experienced late
RILD, classified according to the Radiation Therapy Oncology Group scoring
system. Each patient's computed tomographic (CT) scan was normalized to a single
reference case anatomy (common coordinate system, CCS) through a log
diffeomorphic approach. The obtained deformation fields were used to map the dose
of each patient into the CCS. The coregistration robustness and the dose mapping
accuracy were evaluated by geometric and dose scores. Two different statistical
mapping schemes for nonparametric multiple permutation inference on dose maps
were applied, and the corresponding P<.05 significance lung subregions were
generated. A receiver operating characteristic (ROC)-based test was performed on
the mean dose extracted from each subregion. RESULTS: The coregistration process
resulted in a geometrically robust and accurate dose warping. A significantly
higher dose was consistently delivered to RILD patients in voxel clusters near
the peripheral medial-basal portion of the lungs. The area under the ROC curves
(AUC) from the mean dose of the voxel clusters was higher than the corresponding
AUC derived from the total lung mean dose. CONCLUSIONS: We implemented a
framework including a robust registration process and a VB approach accounting
for the multiple comparison problem in dose-response modeling, and applied it to
a cohort of HL survivors to explore a local dose-RILD relationship in the lungs.
Patients with RILD received a significantly greater dose in parenchymal regions
where low doses (~6 Gy) were delivered. Interestingly, the relation between
differences in the high-dose range and RILD seems to lack a clear spatial
signature.
PMID- 27511853
TI - Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor
Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model.
AB - PURPOSE: To assess the efficacy of 3-week schedules of low-dose pulsed radiation
treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin
(CDDP) in a head and neck squamous cell carcinoma xenograft model. METHODS AND
MATERIALS: Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO
female mice. A total of 30 Gy was administered as 2 Gy/d, 5 d/wk for 3 weeks,
either by PRT (10 * 0.2 Gy/d, with a 3-minute break between each 0.2-Gy dose) or
SRT (2 Gy/d, uninterrupted delivery) in combination with concurrent 2 mg/kg CDDP
3 times per week in the final 2 weeks of radiation therapy. Treatment-induced
growth delays were defined from twice-weekly tumor volume measurements. Tumor
hypoxia was assessed by (18)F-fluoromisonidazole positron emission tomography
imaging, and calculated maximum standardized uptake values compared with tumor
histology. Tumor vessel density and hypoxia were measured by quantitative
immunohistochemistry. Normal tissues effects were evaluated in gut and skin.
RESULTS: Untreated tumors grew to 1000 mm(3) in 25.4 days (+/-1.2), compared with
delays of 62.3 days (+/-3.5) for SRT + CDDP and 80.2 days (+/-5.0) for PRT +
CDDP. Time to reach 2* pretreatment volume ranged from 8.2 days (+/-1.8) for
untreated tumors to 67.1 days (+/-4.7) after PRT + CDDP. Significant differences
in tumor growth delay were observed for SRT versus SRT + CDDP (P=.04), PRT versus
PRT + CDDP (P=.035), and SRT + CDDP versus PRT + CDDP (P=.033), and for survival
between PRT versus PRT + CDDP (P=.017) and SRT + CDDP versus PRT + CDDP (P=.008).
Differences in tumor hypoxia were evident by (18)F-fluoromisonidazole positron
emission tomography imaging between SRT and PRT (P=.025), although not with
concurrent CDDP. Tumor vessel density differed between SRT + CDDP and PRT + CDDP
(P=.011). No differences in normal tissue parameters were seen. CONCLUSIONS:
Concurrent CDDP was more effective in combination PRT than SRT at restricting
tumor growth. Significant differences in tumor vascular density were evident
between PRT and SRT, suggesting a preservation of vascular network with PRT.
PMID- 27511852
TI - Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic
Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical
Study.
AB - PURPOSE: In an effort to develop noninvasive in vivo methods for mapping tumor
oxygenation, magnetic resonance (MR)-derived parameters are being considered,
including global R1, water R1, lipids R1, and R2*. R1 is sensitive to dissolved
molecular oxygen, whereas R2* is sensitive to blood oxygenation, detecting
changes in dHb. This work compares global R1, water R1, lipids R1, and R2* with
pO2 assessed by electron paramagnetic resonance (EPR) oximetry, as potential
markers of the outcome of radiation therapy (RT). METHODS AND MATERIALS: R1, R2*,
and EPR were performed on rhabdomyosarcoma and 9L-glioma tumor models, under air
and carbogen breathing conditions (95% O2, 5% CO2). Because the models
demonstrated different radiosensitivity properties toward carbogen, a growth
delay (GD) assay was performed on the rhabdomyosarcoma model and a tumor control
dose 50% (TCD50) was performed on the 9L-glioma model. RESULTS: Magnetic
resonance imaging oxygen-sensitive parameters detected the positive changes in
oxygenation induced by carbogen within tumors. No consistent correlation was seen
throughout the study between MR parameters and pO2. Global and lipids R1 were
found to be correlated to pO2 in the rhabdomyosarcoma model, whereas R2* was
found to be inversely correlated to pO2 in the 9L-glioma model (P=.05 and .03).
Carbogen increased the TCD50 of 9L-glioma but did not increase the GD of
rhabdomyosarcoma. Only R2* was predictive (P<.05) for the curability of 9L-glioma
at 40 Gy, a dose that showed a difference in response to RT between carbogen and
air-breathing groups. (18)F-FAZA positron emission tomography imaging has been
shown to be a predictive marker under the same conditions. CONCLUSION: This work
illustrates the sensitivity of oxygen-sensitive R1 and R2* parameters to changes
in tumor oxygenation. However, R1 parameters showed limitations in terms of
predicting the outcome of RT in the tumor models studied, whereas R2* was found
to be correlated with the outcome in the responsive model.
PMID- 27511854
TI - Effect of Irradiation on Tumor Microenvironment and Bone Marrow Cell Migration in
a Preclinical Tumor Model.
AB - PURPOSE: To characterize the tumor microenvironment after standard radiation
therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC)
allografts. METHODS AND MATERIALS: Subcutaneous LLC tumors were established in
C57BL/6 mice. Standard RT or PRT was given at 2 Gy/d for a total dose of 20 Gy
using a 5 days on, 2 days off schedule to mimic clinical delivery. Radiation
induced tumor microenvironment changes were examined after treatment using flow
cytometry and antibody-specific histopathology. Normal tissue effects were
measured using noninvasive (18)F-fluorodeoxyglucose positron emission
tomography/computed tomography after naive animals were given whole-lung
irradiation to 40 Gy in 4 weeks using the same 2-Gy/d regimens. RESULTS: Over the
2 weeks of therapy, PRT was more effective than SRT at reducing tumor growth rate
(0.31 +/- 0.02 mm(3)/d and 0.55 +/- 0.04 mm(3)/d, respectively; P<.007).
Histopathology showed a significant comparative reduction in the levels of Ki-67
(14.5% +/- 3%), hypoxia (10% +/- 3.5%), vascular endothelial growth factor (2.3%
+/- 1%), and stromal-derived factor-1alpha (2.5% +/- 1.4%), as well as a
concomitant decrease in CD45(+) bone marrow-derived cell (BMDC) migration (7.8%
+/- 2.2%) after PRT. The addition of AMD3100 also decreased CD45(+) BMDC
migration in treated tumors (0.6% +/- 0.1%). Higher vessel density was observed
in treated tumors. No differences were observed in normal lung tissue after PRT
or SRT. CONCLUSIONS: Pulsed RT-treated tumors exhibited slower growth and reduced
hypoxia. Pulsed RT eliminated initiation of supportive mechanisms utilized by
tumors in low oxygen microenvironments, including angiogenesis and recruitment of
BMDCs.
PMID- 27511855
TI - Computational Modeling of Micrometastatic Breast Cancer Radiation Dose Response.
AB - PURPOSE: Prophylactic cranial irradiation (PCI) involves giving radiation to the
entire brain with the goals of reducing the incidence of brain metastasis and
improving overall survival. Experimentally, we have demonstrated that PCI
prevents brain metastases in a breast cancer mouse model. We developed a
computational model to expand on and aid in the interpretation of our
experimental results. METHODS AND MATERIALS: MATLAB was used to develop a
computational model of brain metastasis and PCI in mice. Model input parameters
were optimized such that the model output would match the experimental number of
metastases per mouse from the unirradiated group. An independent in vivo-limiting
dilution experiment was performed to validate the model. The effect of whole
brain irradiation at different measurement points after tumor cells were injected
was evaluated in terms of the incidence, number of metastases, and tumor burden
and was then compared with the corresponding experimental data. RESULTS: In the
optimized model, the correlation between the number of metastases per mouse and
the experimental fits was >95. Our attempt to validate the model with a limiting
dilution assay produced 99.9% correlation with respect to the incidence of
metastases. The model accurately predicted the effect of whole-brain irradiation
given 3 weeks after cell injection but substantially underestimated its effect
when delivered 5 days after cell injection. The model further demonstrated that
delaying whole-brain irradiation until the development of gross disease
introduces a dose threshold that must be reached before a reduction in incidence
can be realized. CONCLUSIONS: Our computational model of mouse brain metastasis
and PCI correlated strongly with our experiments with unirradiated mice. The
results further suggest that early treatment of subclinical disease is more
effective than irradiating established disease.
PMID- 27511857
TI - The Use of Cone Beam Computed Tomography for Image Guided Gamma Knife
Stereotactic Radiosurgery: Initial Clinical Evaluation.
AB - PURPOSE: The present study used cone beam computed tomography (CBCT) to measure
the inter- and intrafraction uncertainties for intracranial stereotactic
radiosurgery (SRS) using the Leksell Gamma Knife (GK). METHODS AND MATERIALS:
Using a novel CBCT system adapted to the GK radiosurgery treatment unit, CBCT
images were acquired immediately before and after treatment for each treatment
session within the context of a research ethics board-approved prospective
clinical trial. Patients were immobilized in the Leksell coordinate frame (LCF)
for both volumetric CBCT imaging and GK-SRS delivery. The relative displacement
of the patient's skull to the stereotactic reference (interfraction motion) was
measured for each CBCT scan. Differences between the pre- and post-treatment CBCT
scans were used to determine the intrafraction motion. RESULTS: We analyzed 20
pre- and 17 post-treatment CBCT scans in 20 LCF patients treated with SRS. The
mean translational pretreatment setup error +/- standard deviation in the left
right, anteroposterior, and craniocaudal directions was -0.19 +/- 0.32, 0.06 +/-
0.27, and -0.23 +/- 0.2 mm, with a maximum of -0.74, -0.53, and -0.68 mm,
respectively. After an average time between the pre- and post-treatment CBCT
scans of 82 minutes (range 27-170), the mean intrafraction error +/- standard
deviation for the LCF was -0.03 +/- 0.05, -0.03 +/- 0.18, and -0.03 +/- 0.12 mm
in the left-right, anteroposterior, and craniocaudual direction, respectively.
CONCLUSIONS: Using CBCT on a prototype image guided GK Perfexion unit, we were
able to measure the inter- and intrafraction positional changes for GK-SRS using
the invasive frame. In the era of image guided radiation therapy, the use of CBCT
image guidance for both frame- and non-frame-based immobilization systems could
serve as a useful quality assurance tool. Our preliminary measurements can guide
the application of achievable thresholds for inter- and intrafraction discrepancy
when moving to a frameless approach.
PMID- 27511858
TI - Time-Lapse Monitoring of DNA Damage Colocalized With Particle Tracks in Single
Living Cells.
AB - PURPOSE: Understanding the DNA damage and repair induced by hadron therapy (HT)
beams is crucial for developing novel strategies to maximize the use of HT beams
to treat cancer patients. However, spatiotemporal studies of DNA damage and
repair for beam energies relevant to HT have been challenging. We report a
technique that enables spatiotemporal measurement of radiation-induced damage in
live cells and colocalization of this damage with charged particle tracks over a
broad range of clinically relevant beam energies. The technique uses novel
fluorescence nuclear track detectors with fluorescence confocal laser scanning
microscopy in the beam line to visualize particle track traversals within the
subcellular compartments of live cells within seconds after injury. METHODS AND
MATERIALS: We designed and built a portable fluorescence confocal laser scanning
microscope for use in the beam path, coated fluorescence nuclear track detectors
with fluorescent-tagged live cells (HT1080 expressing enhanced green fluorescent
protein tagged to XRCC1, a single-strand break repair protein), placed the entire
assembly into a proton therapy beam line, and irradiated the cells with a fluence
of ~1 * 10(6) protons/cm(2). RESULTS: We successfully obtained confocal images of
proton tracks and foci of DNA single-strand breaks immediately after irradiation.
CONCLUSIONS: This technique represents an innovative method for analyzing
biological responses in any HT beam line at energies and dose rates relevant to
therapy. It allows precise determination of the number of tracks traversing a
subcellular compartment and monitoring the cellular damage therein, and has the
potential to measure the linear energy transfer of each track from therapeutic
beams.
PMID- 27511859
TI - In Regard to Kjems et al.
PMID- 27511856
TI - Image Guided Planning for Prostate Carcinomas With Incorporation of Anti-3
[18F]FACBC (Fluciclovine) Positron Emission Tomography: Workflow and Initial
Findings From a Randomized Trial.
AB - PURPOSE: (18)F-Fluciclovine (anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic
acid) is a novel positron emission tomography (PET)/computed tomography (CT)
radiotracer that has demonstrated utility for detection of prostate cancer. Our
goal is to report the initial results from a randomized controlled trial of the
integration of (18)F-fluciclovine PET-CT into treatment planning for defining
prostate bed and lymph node target volumes. METHODS AND MATERIALS: We report our
initial findings from a cohort of 41 patients, of the first enrolled on a
randomized controlled trial, who were randomized to the (18)F-fluciclovine arm.
All patients underwent (18)F-fluciclovine PET-CT for the detection of metabolic
abnormalities and high-resolution CT for treatment planning. The 2 datasets were
registered first by use of a rigid registration. If soft tissue displacement was
observable, the rigid registration was improved with a deformable registration.
Each (18)F-fluciclovine abnormality was segmented as a percentage of the maximum
standard uptake value (SUV) within a small region of interest around the lesion.
The percentage best describing the SUV falloff was integrated in planning by
expanding standard target volumes with the PET abnormality. RESULTS: In 21 of 55
abnormalities, a deformable registration was needed to map the (18)F-fluciclovine
activity into the simulation CT. The most selected percentage was 50% of maximum
SUV, although values ranging from 15% to 70% were used for specific patients,
illustrating the need for a per-patient selection of a threshold SUV value. The
inclusion of (18)F-fluciclovine changed the planning volumes for 46 abnormalities
(83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the
prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only
9 PET abnormalities were fully contained in the standard target volumes based on
the CT-based segmentations and did not necessitate expansion. CONCLUSIONS: The
use of (18)F-fluciclovine in postprostatectomy radiation therapy planning was
feasible and led to augmentation of the target volumes in the majority (30 of 41)
of the patients studied.
PMID- 27511860
TI - In Reply to Gunn and Garden.
PMID- 27511861
TI - In Regard to Habl et al.
PMID- 27511862
TI - Erratum.
PMID- 27511864
TI - Avoiding unconscious bias.
PMID- 27511863
TI - Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long
term clomiphene citrate treatment.
AB - OBJECTIVES: To determine the relative concentrations of enclomiphene (ENC) and
zuclomiphene (ZUC) isomers in men with hypogonadism on long-term clomiphene
citrate (CC) therapy, and to determine whether patient age, body mass index (BMI)
or duration of therapy were predictive of relative concentrations of ENC and ZUC.
PATIENTS AND METHODS: Men already receiving CC 25 mg daily therapy for secondary
hypogonadism for a minimum of 6 weeks were recruited to have their ENC and ZUC
levels assessed. Total testosterone, free testosterone, oestradiol, follicle
stimulating hormone (FSH), and luteinizing hormone (LH) before initiation of and
while on CC therapy were recorded for all patients. Patient demographics
including age, BMI and medical comorbidites were recorded. Serum samples were
obtained at the time of enrolment to determine ENC and ZUC concentrations.
RESULTS: A total of 15 men were enrolled in the period from June 2015 to August
2015. The median (range) patient age was 36 (22-70) years, BMI 32.0 (21.1-40.3)
kg/m2 and duration of treatment 25.9 (1.7-86.6) months. Baseline median total
testosterone, oestradiol and LH levels were 205.0 ng/dL, 17.0 pg/mL and 4.0
mlU/mL, respectively. The post-treatment median total testosterone, oestradiol
and LH level increased to 488.0 ng/dL, 34.0 pg/mL and 6.1 mIU/mL, respectively
(all P<0.001). The median ENC and ZUC concentrations were 2.2 and 44.0 ng/mL,
respectively. After at least 6 weeks of CC therapy, the median ZUC: ENC serum
concentration ratio was 20:1. On linear regression analysis. patient age, BMI,
duration of treatment and serum testosterone levels were not predictive of ENC or
ZUC concentrations. CONCLUSIONS: Long-term CC therapy resulted in a significant
alteration of ENC and ZUC concentrations, with ZUC as the predominant isomer.
Given the vastly different biochemical and toxicological properties of ENC and
ZUC, this study supports the need for the development of a pure selective
oestrogen receptor antagonist for the treatment of men with hypogonadism.
PMID- 27511865
TI - What's in a Self-report? A Comparison of Pregnant Women with Self-reported and
Hospital Diagnosed Eating Disorder.
AB - The aim of this study was to examine how similar pregnant women with self
reported lifetime eating disorder (ED) were to pregnant women with a hospital
diagnosis of ED. A total of 83 731 pregnant women enrolled in the Danish National
Birth Cohort reported on ED, and by linkage to the Danish health registers,
hospital diagnoses of ED were obtained. Characteristics of women with self
reported ED, hospital diagnosed ED and without ED were compared using chi-square
tests, t-test and logistic regression models with robust standard errors. In
total, 4.8% women reported ED, and 0.5% had a hospital diagnosis of ED recorded
in the health registers. Women with self-reported ED were comparable with women
with hospital diagnosed ED on most reproductive and health characteristics, while
they differed from women without ED concerning all characteristics studied. Our
findings highlight that women with self-reported ED have impaired function and
adverse health outcomes, consistent with diagnosable ED. Copyright (c) 2016 John
Wiley & Sons, Ltd and Eating Disorders Association.
PMID- 27511866
TI - New strategy for improving the diagnostic sensitivity of repetitive nerve
stimulation in myasthenia gravis.
AB - INTRODUCTION: The diagnostic sensitivity of repetitive nerve stimulation (RNS) in
patients with myasthenia gravis (MG) varies as a function of the number of
muscles or the choice of muscles studied. METHODS: By exploring 12 muscles
bilaterally, we evaluated the global sensitivity of RNS at rest, the sensitivity
in different clinical forms, and the sensitivity of different combinations of
muscles studied. RESULTS: The global sensitivity of RNS was 82%, and specificity
was 100%. The sensitivity in the MG subgroups was as follows: ocular (O) = 67%;
oculobulbar (OB) = 86%; and generalized (G) = 89%. The most sensitive muscles
were the anconeus in group O, orbicularis oculi (OO) or nasalis in group OB, and
the trapezius in group G. Maximum sensitivity was obtained by exploring OO,
trapezius, and anconeus bilaterally. CONCLUSIONS: We recommend bilateral
exploration of at least 3 muscles, a facial muscle, trapezius, and anconeus.
Muscle Nerve 55: 532-538, 2017.
PMID- 27511867
TI - Preparation and evaluation of 3 m open tubular capillary columns with a
zwitterionic polymeric porous layer for liquid chromatography.
AB - A 3 m zwitterionic polymeric porous layer open tubular column (3 m * 25 MUm id *
375 MUm od) with a polymeric porous layer thickness of 4 MUm was fabricated by
the copolymerization of [2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)
ammonium hydroxide and N,N'-methylenebis(acrylamide). The effects of the diameter
of the capillary, reaction temperature, and polymerization time on the
preparation of the open tubular column were investigated. Characterized by
scanning electron microscopy, the zwitterionic layer was observed to be rough and
throughout the fused-silica capillary homogenously, which increased the phase
ratio. The separation of neutral, basic, and acidic compounds demonstrates the
strong hydrophilicity of the poly[2-(methacryloyloxy)ethyl] dimethyl-(3
sulfopropyl) ammonium hydroxide coating. In addition, the poly[2
(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide porous layer
open tubular column was applied for the analysis of flavonoids from the rootstalk
of licorice, revealing the potential in separating complex samples. The relative
standard deviation of retention time for run-to-run (n = 5), day-to-day (n = 3),
and column-to-column (n = 3) of toluene, N,N-dimethylformamide, formamide, and
thiourea were below 1.2%, exhibiting good repeatability.
PMID- 27511868
TI - Palladium-Catalyzed Defluorinative Coupling of 1-Aryl-2,2-Difluoroalkenes and
Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes.
AB - The palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes
with boronic acids is described. Broad functional-group tolerance arises from a
redox-neutral process by a palladium(II) active species which is proposed to
undergo a beta-fluoride elimination to afford the products. The
monofluorostilbene products were formed with excellent diastereoselectivity
(>=50:1) in all cases, and it is critical, as traditional chromatographic
techniques often fail to separate monofluoroalkene isomers. As a demonstration of
this method's unique combination of reactivity and functional-group tolerance, a
Gleevec(r) analogue, using a monofluorostilbene as an amide isostere, was
synthesized.
PMID- 27511869
TI - Improved methods for evaluating pre-clinical and histological effects of
subcutaneous fat reduction using high-intensity focused ultrasound in a porcine
model.
AB - BACKGROUND: Non-invasive body sculpting procedures are becoming increasingly
popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat
reduction procedure that permanently destroys unwanted abdominal fat. Despite its
increasing popularity, evaluation methods for the procedure have not yet been
fully developed. AIMS: The objective of this study was to develop evaluation
methods for HIFU for non-surgical, permanent fat reduction in the anterior
abdomen using a porcine model. METHODS: The abdomens of female pigs (Sus scrofa,
n = 7) were treated with a HIFU device (SCIZERTM , Classys Inc, Seoul, Korea). We
examined treatment effects using photography, ultrasound, gross and microscopic
pathology, and serum lipid and liver function level analysis, carbon tracer test,
and histological examination in order to determine the mechanism of action,
efficacy, and safety of the procedure. RESULTS: HIFU treatment effectively
reduced abdominal fat in a porcine model; it accurately treated the target
subcutaneous fat layer and the subcutaneous fat was reduced effectively via
ultrasonic measurement after HIFU treatment. On histological staining (H&E,
toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous
fat reduction occurred effectively via accurate treatment of the targeted
subcutaneous fat layer. On hematological assay, there were changes within normal
range, and values remained stable after 48 h. Via carbon tracer test, the
migration of activated macrophages was identified within the axillary lymph node
(LN). PPAR-delta, a protein defined by immunohistochemistry staining, was
overexpressed in the early stage on days 1 and 7, but a gradual decreasing
pattern was confirmed. CONCLUSION: We successfully used a HIFU device for body
contouring and fat reduction in a pre-clinical study. These results provide that
the essential clues toward the effective evaluation, guiding selection of the
appropriate diagnostic investigations.
PMID- 27511870
TI - Near infrared photoimmunotherapy of B-cell lymphoma.
AB - Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer
theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has
successfully treated preclinical tumor models with APCs and is now in the first
in-human phase 1 clinical trial for head and neck cancer patients against EGFR.
CD20 is highly expressed in many B-cell lymphomas and is emerging as a molecular
target for this disease. Here, we describe the use of the anti-CD20 monoclonal
antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20
expressing lymphoma mouse models. CD20 expressing B-cell lymphoma cell lines
(Daudi and Ramos) were used in this study. Rituximab-IR700, rituximab conjugated
with IRDye700DX, showed specific binding, and cell-specific killing only after
exposure of NIR light to both cells in vitro. To evaluate effects of NIR-PIT in
vivo, tumor-bearing mice were separated into 4 groups: (1) control; (2) APC i.v.
only; (3) NIR light exposure only; (4) APC and NIR light (NIR-PIT). These were
performed every week for up to 3 weeks. Rituximab-IR700 showed high tumor
accumulation and high target-to-background ratio in vivo. Tumor growth was
significantly inhibited by NIR-PIT in comparison with the other groups (p < 0.001
for both tumors), and survival was significantly prolonged in both tumors (p <
0.001 for Daudi tumors and p < 0.0001 for Ramos tumors vs other groups). More
than half of tumors were cured with this single regimen of NIR-PIT. In
conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT
against B-cell lymphoma.
PMID- 27511872
TI - Self-regulatory speech during planning and problem-solving in children with SLI
and their typically developing peers.
AB - BACKGROUND: Past research with children with specific language impairment (SLI)
has shown them to have poorer planning and problem-solving ability, and delayed
self-regulatory speech (SRS) relative to their typically developing (TD) peers.
However, the studies are few in number and are restricted in terms of the number
and age range of participants, which limits our understanding of the nature and
extent of any delays. Moreover, no study has examined the performance of a
significant subset of children with SLI, those who have hyperactive and
inattentive behaviours. AIMS: This cross-sectional study aimed to compare the
performance of young children with SLI (aged 4-7 years) with that of their TD
peers on a planning and problem-solving task and to examine the use of SRS while
performing the task. Within each language group, the performance of children with
and without hyperactive and inattentive behaviours was further examined. METHODS
& PROCEDURES: Children with SLI (n = 91) and TD children (n = 81), with and
without hyperactive and inattentive behaviours across the three earliest school
years (Kindergarten, Preprimary and Year 1) were video-taped while they completed
the Tower of London (TOL), a planning and problem-solving task. Their recorded
speech was coded and analysed to look at differences in SRS and its relation to
TOL performance across the groups. MAIN CONTRIBUTION: Children with SLI scored
lower on the TOL than TD children. Additionally, children with hyperactive and
inattentive behaviours performed worse than those without hyperactive and
inattentive behaviours, but only in the SLI group. This suggests that children
with SLI with hyperactive and inattentive behaviours experience a double deficit.
Children with SLI produced less inaudible muttering than TD children, and showed
no reduction in social speech across the first three years of school. Finally,
for children with SLI, a higher percentage performed better on the TOL when they
used SRS than when they did not. CONCLUSIONS & IMPLICATIONS: The results point
towards a significant delay in the development and internalization of SRS in the
SLI group, which should be taken into account when considering the planning and
problem-solving of young children with SLI.
PMID- 27511871
TI - A ribonucleotide reductase inhibitor with deoxyribonucleoside-reversible
cytotoxicity.
AB - Ribonucleotide Reductase (RNR) is the sole enzyme that catalyzes the reduction of
ribonucleotides into deoxyribonucleotides. Even though RNR is a recognized target
for antiproliferative molecules, and the main target of the approved drug
hydroxyurea, few new leads targeted to this enzyme have been developed. We have
evaluated a recently identified set of RNR inhibitors with respect to inhibition
of the human enzyme and cellular toxicity. One compound, NSC73735, is
particularly interesting; it is specific for leukemia cells and is the first
identified compound that hinders oligomerization of the mammalian large RNR
subunit. Similar to hydroxyurea, it caused a disruption of the cell cycle
distribution of cultured HL-60 cells. In contrast to hydroxyurea, the disruption
was reversible, indicating higher specificity. NSC73735 thus defines a potential
lead candidate for RNR-targeted anticancer drugs, as well as a chemical probe
with better selectivity for RNR inhibition than hydroxyurea.
PMID- 27511874
TI - Natural exposure to domoic acid causes behavioral perseveration in Wild Sea
lions: Neural underpinnings and diagnostic application.
AB - Domoic acid is a naturally occurring algal toxin that causes neurological
symptoms and mortality in exposed marine life. California sea lions (Zalophus
californianus) are the most visible victims, and suffer epilepsy and progressive
hippocampal atrophy. Despite its reliable neurological effects, little is known
about how exposure to domoic acid alters behavior, which is critical for
understanding the impact of toxic exposure on long-term survival in sea lions and
other exposed animals, including humans. Better understanding of the behavioral
effects may also inform veterinary diagnosis and treatment. Anecdotally, exposed
sea lions have been reported to show enhanced perseverative behavior. To assess
the neurobehavioral effects of domoic acid, we compared veterinary diagnoses,
measures of hippocampal volume from in vivo MRI, and behavioral measures of
habituation and dishabituation in 27 wild sea lions undergoing rehabilitation.
The sample was divided post-hoc between subjects with clear veterinary diagnoses
of chronic domoic acid toxicosis and those with no evidence of the disease. In
the behavioral task, subjects were exposed repeatedly to sounds from two source
locations, and, following a short delay, exposed again. Veterinary diagnosis of
domoic acid toxicosis was associated with extent of hippocampal damage, predicted
delayed habituation in phase 1, and enhanced dishabituation in phase 2. Receiver
operating characteristic analysis indicated that delayed habituation in phase 1
was diagnostically predictive. Enhanced dishabituation in phase 2 was correlated
with reduced right ventral hippocampal volume. Together, delayed habituation and
enhanced dishabituation following domoic acid exposure indicate a clinically
relevant and potentially maladaptive behavioral pattern of perseveration.
PMID- 27511873
TI - A point mutation in AgrC determines cytotoxic or colonizing properties associated
with phenotypic variants of ST22 MRSA strains.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of skin and
soft tissue infections. One of the highly successful and rapidly disseminating
clones is MRSA ST22 commonly associated with skin tropism. Here we show that a
naturally occurring single amino acid substitution (tyrosine to cysteine) at
position 223 of AgrC determines starkly different ST22 S. aureus virulence
phenotypes, e.g. cytotoxic or colonizing, as evident in both in vitro and in vivo
skin infections. Y223C amino acid substitution destabilizes AgrC-AgrA interaction
leading to a colonizing phenotype characterized by upregulation of bacterial
surface proteins. The colonizing phenotype strains cause less severe skin tissue
damage, show decreased susceptibility towards the antimicrobial LL-37 and induce
autophagy. In contrast, cytotoxic strains with tyrosine at position 223 of AgrC
cause infections characterized by inflammasome activation and severe skin tissue
pathology. Taken together, the study demonstrates how a single amino acid
substitution in the histidine kinase receptor AgrC of ST22 strains determines
virulence properties and infection outcome.
PMID- 27511875
TI - Surface roughness and adaptation of different materials to secure implant
attachment housings.
AB - STATEMENT OF PROBLEM: Various materials are available to secure implant
attachment housings in overdentures. Surface roughness and the adaptation of
these materials to the denture base and the housings may increase the microcracks
and bacterial adhesion at the interfaces in the long term. The surface
characteristics of the interface between the denture base orientation material
and the attachment housing have not been extensively studied. PURPOSE: The
purpose of this in vitro study was to evaluate the surface roughness and the
adaptation of 5 different housing orientation materials to the housings and the
denture base. MATERIAL AND METHODS: Fifty-five poly(methyl methacrylate) (PMMA)
specimens (15 mm in diameter and 4 mm in height) were prepared with a clearance
inside to allow the insertion of overdenture housings. Five different materials
were used for housing orientation (Quick Up, Ufi Gel Hard, Tokuyama Rebase II
Fast, Meliodent, and Paladent). The specimens were thermocycled 5000 times
between 5 degrees C and 55 degrees C. The surface roughness (Ra values) of the
specimens was measured with a noncontact profilometer. Scanning electron images
were made in order to inspect the PMMA-orientation material-housing interfaces.
The Kruskal-Wallis test was used to investigate the differences between the
surface roughness values of the orientation materials, and the Iman-Conover test
was used for pairwise comparisons (alpha=.05). RESULTS: The surface roughness
values significantly differed between Quick up and Ufi Gel orientation materials
only, and Quick up had smaller surface roughness values than Ufi Gel (P=.009).
Microcracks were observed among the groups only at the junction of the
orientation material and the housing after thermocycling. CONCLUSIONS: Ufi Gel
Hard showed the roughest surfaces around the overdenture attachment housings. The
adaptation between the orientation material and the housing may deteriorate, and
increased surface roughness and microcrack formation may be seen around the
housings.
PMID- 27511876
TI - Complete mouth rehabilitation and gastroesophageal reflux disease: Conventional
and contemporary treatment approaches.
AB - This report describes the diagnosis and prosthodontic management of 2 patients
with a history of chronic gastroesophageal reflux disease and worn dentition.
Different treatment approaches were used for oral rehabilitation. Use of
conventional and contemporary restorative materials resulted in functional and
esthetic prosthodontic rehabilitation with a favorable prognosis.
PMID- 27511877
TI - Masticatory efficiency and muscular activity in removable partial dental
prostheses with different cusp angles.
AB - STATEMENT OF PROBLEM: The loss of posterior teeth has a negative effect on the
masticatory efficiency and activity of mastication muscles. How these muscles are
affected by partial removable dental prostheses (PRDPs) with different cusp
angles is unknown. PURPOSE: The purpose of this clinical study was to evaluate
the influence of different cusp angles, with anatomic (33 degrees), semianatomic
(20 degrees), and nonanatomic teeth (0 degree), on the masticatory efficiency and
muscular activity of participants receiving mandibular bilateral distal PRDPs.
MATERIAL AND METHODS: Fifteen participants consented to the evaluation of
masticatory efficiency and electromyographic (EMG) activity with a PRDP with a
unified bilateral design. The cusp angles of the artificial teeth were randomly
changed from anatomic (33 degrees), semianatomic (20 degrees), and nonanatomic
teeth (0 degree). Masticatory efficiency was evaluated by recording 5 parameters,
including number of strokes, and time of mastication while the EMG activities of
the masseter and temporalis muscles, measured using surface electromyography. The
data were analyzed with 1-way ANOVA and the Tukey multiple post hoc test with
statistical software (alpha=.05). RESULTS: With regard to masticatory efficiency,
PRDPs with anatomic and semianatomic teeth exhibited higher masticatory
efficiency than those with nonanatomic teeth, whereas no significant differences
were found between PRDPs with anatomic and semianatomic teeth. With respect to
EMG activity, the least EMG activity was observed in PRDPs with anatomic teeth,
whereas the highest activity was observed with nonanatomic teeth. No significant
differences were found between the effect of PRDPs with anatomic and semianatomic
teeth on masseter activity. CONCLUSIONS: Changing the cusp angle from 33 to 20
degrees in PRDPs did not influence the masticatory efficiency or the EMG activity
of the masseters. However, it did lead to increased EMG activities of the
temporalis muscle. PRDPs with nonanatomic teeth were associated with a
significant decrease in masticatory efficiency accompanied by a significant
increase in EMG activity.
PMID- 27511878
TI - In vitro effects of acid challenge on incisal/occlusal cupping/cratering.
AB - STATEMENT OF PROBLEM: The cause of occlusal/incisal cupping/cratering (depressed
dentin surrounded by elevated rims of enamel) has been postulated to be primarily
the effect of acid on exposed dentin. It is hypothesized that abrasion, bruxism,
attrition, and stress-corrosion may play a secondary role in lesion formation.
The primary cause and sequence of occlusal/incisal cupping/cratering remain
scientifically controversial. PURPOSE: The purpose of this in vitro study was to
determine the effects of acid on human enamel, mantle dentin, and peritubular
dentin in the creation of incisal/occlusal cupping/cratering. This study was
designed to visually illustrate the role of acid in the formation of
cupping/cratering. MATERIAL AND METHODS: A soft compact toothbrush was tested
using both high relative dentin abrasivity (RDA)- and low-RDA dentifrices and
water only (nonabrasive) on extracted human teeth. Seventeen specimens of 4 teeth
each (68 teeth) were subjected to horizontal brushing with a 1:1 dentifrice-to
water slurry or water only. Twelve of these 17 specimens, a total of 48 teeth,
were subjected to acid challenge. Each of these 12 specimens were brushed for 500
strokes after each acid challenge for a total of 150000 strokes and 300 acid
immersions. Half the specimens were acid challenged for 5 minutes and the other
half for 10 minutes between brushings. RESULTS: No visible loss of tooth
structure was noted in the control specimens brushed in water only. The control
specimens brushed in a 1:1 slurry of toothpaste/water demonstrated
incisal/occlusal cupping/cratering. The acid-challenged specimens brushed in
water only demonstrated enamel and peritubular dentin loss with elevated rims
and/or plateaus of mantle dentin, the opposite of occlusal/incisal
cupping/cratering. All specimens brushed with the higher abrasive dentifrice
demonstrated visible wear of enamel, mantle, and peritubular dentin, culminating
in occlusal/incisal cupping/cratering. Surprisingly, those acid-challenged
specimens brushed with the lower abrasive toothpaste demonstrated visible wear of
the enamel and peritubular dentin, resulting in elevated rims and/or plateaus of
mantle dentin. CONCLUSIONS: Acid affects both the enamel and the mineralized
component of dentin. This study demonstrated that incisal/occlusal
cupping/cratering occurring in worn dentition can be caused by the use of
dentifrice alone. Acid challenge affects the inorganic components of tooth
structure but not the organic components and so does not cause the dentinal
cupping/cratering of the incisal/occlusal surfaces of the human dentition.
PMID- 27511879
TI - Numeric simulation of occlusal interferences in molars restored with ultrathin
occlusal veneers.
AB - STATEMENT OF PROBLEM: Selecting material for a minimally invasive occlusal veneer
reconstruction concept requires an understanding of how stresses are distributed
during functional and parafunctional forces. PURPOSE: The purpose of this in
vitro study was to investigate stress distribution in a maxillary molar restored
with ultrathin occlusal veneers and subjected by an antagonistic mandibular molar
to clenching and working and nonworking movements. MATERIAL AND METHODS: A
maxillary first molar was modeled from microcomputed tomography (micro-CT) data,
using medical image processing software, stereolithography editing/optimizing
software, and finite element software. Simulated ultrathin occlusal veneer
materials were used. The mandibular molar antagonist was a solid nondeformable
geometric entity. Loads simulated clenching, working, and nonworking movements
with loading of 500 N. The values of the maximum principal stress were recorded.
RESULTS: In the clenching load situation, maximum tensile stresses were located
at the occlusal veneer (52 MPa for composite resin versus 47 MPa for ceramic). In
the working movement, significant additional tensile stresses were found on the
palatal root (87 MPa for composite resin and 85 MPa for ceramic). In the
nonworking movement, tensile stress on the ultrathin occlusal veneer increased to
118 MPa for composite resin and 143 MPa for ceramic veneers. Tensile stress peaks
shifted to the mesiobuccal root (75 MPa for composite resin and 74 MPa for
ceramic). CONCLUSIONS: The topography of stresses generated by the various
occlusal interferences were clearly identified. Significant tensile stress
concentrations were found within the restoration's occlusal topography and root,
with the nonworking interference being the most harmful and also the most
revealing of the difference between the composite resin and ceramic ultrathin
occlusal veneers.
PMID- 27511880
TI - Effects of Obesity and Hypertension on Pulse Wave Velocity in Children.
AB - Pulse wave velocity (PWV) is a biomarker of arterial stiffness. Findings from
prior studies are conflicting regarding the impact of obesity on PWV in children.
The authors measured carotid-femoral PWV in 159 children aged 4 to 18 years, of
whom 95 were healthy, 25 were obese, 15 had hypertension (HTN), and 24 were both
obese and hypertensive. Mean PWV increased with age but did not differ by race or
sex. In adjusted analyses in children 10 years and older (n=102), PWV was
significantly higher in children with hypertension (PWV+/-standard deviation,
4.9+/-0.7 m/s), obesity (5.0+/-0.9 m/s), and combined obesity-hypertension (5.2+/
0.6 m/s) vs healthy children (4.3+/-0.7 m/s) (each group, P<.001 vs control). In
our study, obesity and HTN both significantly and independently increased PWV,
while African American children did not have a higher PWV than Caucasian
children.
PMID- 27511881
TI - 3D Cross-Point Plasmonic Nanoarchitectures Containing Dense and Regular Hot Spots
for Surface-Enhanced Raman Spectroscopy Analysis.
AB - 3D stacking of plasmonic nanostructures is achieved using a solvent-assisted
nanotransfer printing (S-nTP) technique to provide extremely dense and regular
hot spot arrays for highly sensitive surface-enhanced Raman spectroscopy (SERS)
analysis. Moreover, hybrid plasmonic nanostructures obtained by printing the
nanowires on a continuous metal film or graphene surface show significantly
intensified SERS signals due to vertical plasmonic coupling.
PMID- 27511882
TI - Comparison of microbubble presence in the right heart during mechanochemical and
radiofrequency ablation for varicose veins.
AB - Objective Mechanochemical ablation is a novel technique for ablation of varicose
veins utilising a rotating catheter and liquid sclerosant. Mechanochemical
ablation and radiofrequency ablation have no reported neurological side-effect
but the rotating mechanism of mechanochemical ablation may produce microbubbles.
Air emboli have been implicated as a cause of cerebrovascular events during
ultrasound-guided foam sclerotherapy and microbubbles in the heart during
ultrasound-guided foam sclerotherapy have been demonstrated. This study
investigated the presence of microbubbles in the right heart during varicose vein
ablation by mechanochemical abaltion and radiofrequency abaltion. Methods
Patients undergoing great saphenous vein ablation by mechanochemical abaltion or
radiofrequency ablation were recruited. During the ablative procedure, the
presence of microbubbles was assessed using transthoracic echocardiogram. Offline
blinded image quantification was performed using International Consensus Criteria
grading guidelines. Results From 32 recruited patients, 28 data sets were
analysed. Eleven underwent mechanochemical abaltion and 17 underwent
radiofrequency abaltion. There were no neurological complications. In total, 39%
(11/28) of patients had grade 1 or 2 microbubbles detected. Thirty-six percent
(4/11) of mechanochemical abaltion patients and 29% (5/17) of radiofrequency
ablation patients had microbubbles with no significant difference between the
groups ( p=0.8065). Conclusion A comparable prevalence of microbubbles between
mechanochemical abaltion and radiofrequency ablation both of which are lower than
that previously reported for ultrasound-guided foam sclerotherapy suggests that
mechanochemical abaltion may not confer the same risk of neurological events as
ultrasound-guided foam sclerotherapy for treatment of varicose veins.
PMID- 27511883
TI - Parkes Weber syndrome-Diagnostic and management paradigms: A systematic review.
AB - Objectives Parkes Weber syndrome is a congenital vascular malformation which
consists of capillary malformation, venous malformation, lymphatic malformation,
and arteriovenous malformation. Although Parkes Weber syndrome is a clinically
distinctive entity with serious complications, it is still frequently
misdiagnosed as Klippel-Trenaunay syndrome that consists of the triad capillary
malformation, venous malformation, and lymphatic malformation. Methods We
performed a systematic review investigating clinical, diagnostic, and treatment
modalities of Parkes Weber syndrome (PubMed/MEDLINE, Embase, and Cochrane
databases). Thirty-six publications (48 patients) fulfilled the eligibility
criteria. Results The median age of patients was 23 years (IQR, 8-32), and 24
(50.0%) were males. Lower extremity was affected in 42 (87.5%) and upper
extremity in 6 (12.5%) patients; 15 (31.3%) patients developed high-output heart
failure; 12 (25.0%) patients had chronic venous ulcerations, whereas 4 (8.3%)
manifested distal arterial ischemia. The spinal arteriovenous malformations were
reported in six (12.5%) patients and coexistence of aneurysmatic disease in five
(10.4%) patients. The most frequently utilized invasive treatments were
embotherapy followed by amputation and surgical arteriovenous malformation
resection, and occasionally stent-graft implantation. All modalities showed
clinical improvement. However, long follow-up and outcome remained unclear.
Conclusion A diagnosis of Parkes Weber syndrome should be made on the presence of
capillary malformation, venous malformation, lymphatic malformation, and
arteriovenous malformation (as main defect) in overgrowth extremity.
Arteriovenous malformation presents the criterion for distinguishing Parkes Weber
syndrome from Klippel-Trenaunay syndrome, which is substantial for treatment
strategy. The primary management goal should be patient's quality of life
improvement and complication reduction. Embolization alone/combined with surgical
resection targeting occlusion or removal of arteriovenous malformation "nidus"
reliably leads to clinical improvement.
PMID- 27511884
TI - CD14/TLR4 priming potentially recalibrates and exerts anti-tumor efficacy in
tumor associated macrophages in a mouse model of pancreatic carcinoma.
AB - Pancreatic cancer is the fourth major cause of cancer related deaths in the world
and 5 year survival is below 5%. Among various tumor directed therapies,
stimulation of Toll-like receptors (TLR) has shown promising effects in various
tumor models. However, pancreatic cancer cells frequently express these receptors
themselves and their stimulation (TLR 2 and/or 4 particularly) within tumor
microenvironment is known to potentially enhance tumor cell proliferation and
cancer progression. Consistent stimulation of tumor associated macrophages
(TAMs), in particular with tumor derived TLR ligand within the tumor
microenvironment promotes cancer related inflammation, which is sterile, non
immunogenic and carcinogenic in nature. In view of this, recalibrating of TAM has
the potential to induce immunogenic inflammation. Consistent with this, we
provide experimental evidence for the first time in this study that priming of
TAMs with TLR4 ligend (LPS) alone or in combination with IFN-gamma not only
recalibrates pancreatic tumor cells induced M2 polarization, but also confers
anti-tumor potential in TAMs. Most interestingly, reduced tumor growth in
macrophage depleted animals suggests that macrophage directed approaches are
important for the management of pancreatic tumors.
PMID- 27511886
TI - Associations of the CYP3A5*3 and CYP3A4*1G polymorphisms with the
pharmacokinetics of oral midazolam and the urinary 6beta-hydroxycortisol/cortisol
ratio as markers of CYP3A activity in healthy male Chinese.
AB - WHAT IS KNOWN AND OBJECTIVE: The oral plasma clearance of midazolam and the ratio
of 6beta-hydroxycortisol (6beta-OHF) to cortisol (F) in urine are two potential
markers for evaluating CYP3A activity in vivo. We assessed the influence of two
common CYP3A polymorphisms on the pharmacokinetics of oral midazolam and urinary
ratio of 6beta-OHF/F in healthy Chinese. METHODS: Single oral 15 mg doses of
midazolam were given to 20 healthy male Chinese subjects who were genotyped for
the CYP3A5*3 and CYP3A4*1G polymorphisms. The plasma concentrations of midazolam
were determined by LC/MS/MS. Morning urine samples were collected after overnight
fasting, and urine F and 6beta-OHF concentrations were measured using UPLC.
RESULTS AND DISCUSSION: There were no significant correlations between the
pharmacokinetic parameters of midazolam and urinary ratios of 6beta-OHF/F. The
CYP3A polymorphisms examined had no significant associations with the urinary
ratios of 6beta-OHF/F or the pharmacokinetics of midazolam. However, diplotype
analysis suggested that CYP3A5 expressers with the CYP3A4*1/*1G genotype (n = 3)
had significantly lower midazolam AUC0-infinity values (210.0 +/- 33.5 vs. 313.9
+/- 204.6 h?ng/mL, P = 0.044) and higher CL/F values (1.16 +/- 0.16 vs. 0.88 +/-
0.48 L/h/kg, P = 0.005) compared to subjects with the CYP3A4*1/*1 genotype (n =
4), which is consistent with some previous studies with tacrolimus. WHAT IS NEW
AND CONCLUSION: There were no significant associations between midazolam
pharmacokinetic parameters and urinary ratios of 6beta-OHF/F and the two CYP3A
polymorphisms were not associated with the urinary ratios of 6beta-OHF/F or
midazolam pharmacokinetic parameters. The possible association of CYP3A5*3 and
CYP3A4*1G polymorphisms on CYP3A activity and their potential interaction require
confirmation in a larger study.
PMID- 27511887
TI - Clinical effects of internal fixation for ulnar styloid fractures associated with
distal radius fractures: A matched case-control study.
AB - BACKGROUND: Ulnar styloid fractures are often associated with distal radius
fractures. However, controversy exists regarding whether to treat ulnar styloid
fractures. This study aimed to evaluate clinical effects of internal fixation for
ulnar styloid fractures after distal radius fractures were treated with the volar
locking plate system. METHODS: We used prospectively collected data of distal
radius fractures. 111 patients were enrolled in this study. A matched case
control study design was used. We selected patients who underwent fixation for
ulnar styloid fractures (case group). Three control patients for each patient of
the case group were matched on the basis of age, sex, and fracture type of distal
radius fractures from among patients who did not undergo fixation for ulnar
styloid fractures (control group). The case group included 16 patients (7 men, 9
women; mean age: 52.6 years; classification of ulnar styloid fractures: center,
3; base, 11; and proximal, 2). The control group included 48 patients (15 men, 33
women; mean age: 61.1 years; classification of ulnar styloid fractures: center,
10; base, 31; and proximal, 7). For radiographic examination, the volar tilt
angle, radial inclination angle, and ulnar variance length were measured, and the
union of ulnar styloid fractures was judged. For clinical examination, the range
of motions, grip strength, Hand20 score, and Numeric Rating Scale score were
evaluated. RESULTS: There was little correction loss for each radiological
parameter of fracture reduction, and these parameters were not significantly
different between the groups. The bone-healing rate of ulnar styloid fractures
was significantly higher in the case group than in the control group, but the
clinical results were not significantly different. CONCLUSIONS: We revealed that
there was no need to fix ulnar styloid fractures when distal radius fractures
were treated via open reduction and internal fixation with a volar locking plate
system.
PMID- 27511888
TI - MnO2-induced synthesis of fluorescent polydopamine nanoparticles for reduced
glutathione sensing in human whole blood.
AB - Polydopamine (PDA) nanoparticles, as a kind of popular polymer material, have
attracted a great deal of attention from various areas including materials
science, biomedicine, energy, environmental science and so on owing to their
striking physicochemical properties. Herein, we reported for the first time the
synthesis of intrinsic fluorescent PDA nanoparticles using MnO2 as an oxidant. In
the presence of MnO2, dopamine was quickly oxidized into its quinone derivative,
and autopolymerized into fluorescent PDA nanoparticles. Using fluorescent PDA
nanoparticles as a fluorescence signal indicator, we further established a cost
effective sensor for rapid, sensitive and selective sensing of reduced
glutathione (GSH) based on the redox reaction between MnO2 and GSH, and the key
role of MnO2 in the formation of fluorescent PDA nanoparticles. GSH has the
capability of reducing MnO2 into Mn(2+), which inhibited the formation of the
fluorescent PDA nanoparticles. Thus, the concentration of GSH was directly
related to the decreased fluorescence signal intensity of the PDA nanoparticles.
The sensor showed good sensing performance for GSH detection with high
sensitivity and desirable selectivity over other potential interfering species.
Additionally, the sensor exhibited excellent practical applications for GSH
detection in human whole blood samples, which presents potential applications in
biological detection and clinical diagnosis.
PMID- 27511885
TI - Regulation of energy homeostasis by the ubiquitin-independent REGgamma
proteasome.
AB - Maintenance of energy homeostasis is essential for cell survival. Here, we report
that the ATP- and ubiquitin-independent REGgamma-proteasome system plays a role
in maintaining energy homeostasis and cell survival during energy starvation via
repressing rDNA transcription, a major intracellular energy-consuming process.
Mechanistically, REGgamma-proteasome limits cellular rDNA transcription and
energy consumption by targeting the rDNA transcription activator SirT7 for
ubiquitin-independent degradation under normal conditions. Moreover, energy
starvation induces an AMPK-directed SirT7 phosphorylation and subsequent REGgamma
dependent SirT7 subcellular redistribution and degradation, thereby further
reducing rDNA transcription to save energy to overcome cell death. Energy
starvation is a promising strategy for cancer therapy. Our report also shows that
REGgamma knockdown markedly improves the anti-tumour activity of energy
metabolism inhibitors in mice. Our results underscore a control mechanism for an
ubiquitin-independent process in maintaining energy homeostasis and cell
viability under starvation conditions, suggesting that REGgamma-proteasome
inhibition has a potential to provide tumour-starving benefits.
PMID- 27511889
TI - Analysis of an astounding aggregation of Ranzania laevis (Molidae:
Actinopterygii) in the tropical south-western Atlantic.
AB - Unusual catches of more than 4200 kg of the slender sunfish Ranzania laevis are
described from the south-western Atlantic, corresponding to the largest
aggregation records for the species. These unexpected records were associated
with unusually warm currents in the area. Males and females were physiologically
able to spawn at the moment of capture, suggesting the occurrence of reproductive
aggregation in this species.
PMID- 27511890
TI - Recombinant porcine sequence factor VIII (rpFVIII) for acquired haemophilia A:
practical clinical experience of its use in seven patients.
AB - INTRODUCTION: A recombinant porcine factor VIII B-domain-deleted product
(rpFVIII; OBIZUR, Baxalta Incorporated, Deerfield, IL 60015, USA) was recently
approved for treatment of bleeding episodes in adults with acquired haemophilia A
(AHA) in the United States. To date, no clinical experience outside the
registration study has been reported. AIM: To describe early clinical experience
using rpFVIII for AHA. METHODS: A retrospective chart review of seven patients
with AHA treated with rpFVIII at four institutions from November 2014 to October
2015. RESULTS: The time to diagnosis of AHA ranged from 5 days to 6 weeks. Six
major and one other bleed were treated with rpFVIII following unsatisfactory
bypassing agent (BPA) therapy. Good haemostatic efficacy was seen in five of
seven cases. rpFVIII loading doses of 100 (n = 6) or 200 U kg-1 (n = 1) increased
FVIII activity from <1 to 9% at baseline to 109-650% within 0.25-7 h in six of
seven cases. Subsequent median doses ranged from 30 to 100 U kg-1 for 3-26 days.
No rpFVIII-related adverse events were reported. Three patients survived with
inhibitor eradication, one with persistent inhibitor, two died with inhibitors
present and one was discharged and later died from unrelated causes. CONCLUSIONS:
rpFVIII showed good haemostatic efficacy with no recurrences in most cases, with
consumption substantially less than in the registration study. Treatment
decisions were based on FVIII activity levels and clinical assessment. The
ability to titrate rpFVIII dose using FVIII activity was considered advantageous
compared with BPA therapy. Notable delays in diagnosis were observed.
PMID- 27511891
TI - Synovial fluid pretreatment with hyaluronidase facilitates isolation of CD44+
extracellular vesicles.
AB - Extracellular vesicles (EVs) in synovial fluid (SF) are gaining increased
recognition as important factors in joint homeostasis, joint regeneration, and as
biomarkers of joint disease. A limited number of studies have investigated EVs in
SF samples of patients with joint disease, but knowledge on the role of EVs in
healthy joints is lacking. In addition, no standardized protocol is available for
isolation of EVs from SF. Based on the high viscosity of SF caused by high
concentrations of hyaluronic acid (HA) - a prominent extracellular matrix
component - it was hypothesized that EV recovery could be optimized by
pretreatment with hyaluronidase (HYase). Therefore, the efficiency of EV
isolation from healthy equine SF samples was tested by performing sequential
ultracentrifugation steps (10,000g, 100,000g and 200,000g) in the presence or
absence of HYase. Quantitative EV analysis using high-resolution flow cytometry
showed an efficient recovery of EVs after 100,000g ultracentrifugation, with an
increased yield of CD44+ EVs when SF samples were pretreated with HYase.
Morphological analysis of SF-derived EVs with cryo-transmission-electron
microscopy did not indicate damage by high-speed ultracentrifugation and revealed
that most EVs are spherical with a diameter of 20-200 nm. Further protein
characterization by Western blotting revealed that healthy SF-derived EVs contain
CD9, Annexin-1, and CD90/Thy1.1. Taken together, these data suggest that EV
isolation protocols for body fluids that contain relatively high amounts of HA,
such as SF, could benefit from treatment of the fluid with HYase prior to
ultracentrifugation. This method facilitates recovery and detection of CD44+ EVs
within the HA-rich extracellular matrix. Furthermore, based on the findings
presented here, it is recommended to sediment SF-derived EVs with at least
100,000g for optimal EV recovery.
PMID- 27511892
TI - Coexistence of acquired hemophilia A and epidermolysis bullosa acquisita: Two
case reports and published work review.
AB - Epidermolysis bullosa acquisita (EBA) is a rare chronic subepidermal bullous
autoimmune disease. The occurrence of acquired hemophilia A (AHA) is low and so
the coexistence of EBA and AHA is extremely rare. We herein described a case of
EBA coexisting with AHA and a case of EBA coexisting with AHA and hepatitis B.
These EBA may be related to the pathogenesis of AHA. In this study, we analyzed
the clinical features in the two Chinese cases of EBA coexisting with AHA, and
found esophageal hemorrhage and hematemesis were the main symptoms of both
patients. Cyclosporin, prednisone and lamivudine effectively control EBA with AHA
and hepatitis B. The dose of cyclosporin should be more than 4 mg/kg per day and
the period of treatment should be longer than 5 months to reduce the risk of EBA
co-occurring with AHA.
PMID- 27511893
TI - Rearing environment differentially modulates cocaine self-administration after
opioid pretreatment: A behavioral economic analysis.
AB - BACKGROUND: Research has shown that previous experiences during development,
especially if stressful, can alter an organism's response to opioids later in
life. Given the previous literature on opioid modulation of cocaine self
administration, the current study raised rats in either an enriched condition
(EC) or isolated condition (IC) and employed behavioral economics to study the
effects of naltrexone and morphine on cocaine self-administration. METHODS: EC
and IC rats were trained to lever press for cocaine using a within-session demand
procedure. This procedure measured cocaine consumption under changing cocaine
price by decreasing the dose of cocaine earned throughout a session. Rats were
able to self-administer cocaine on a FR1; every 10min the cocaine dose was
systematically decreased (0.75-0.003mg/kg/infusion cocaine). After reaching
stability on this procedure, rats were randomly pretreated with 0, 0.3, 1, or
3mg/kg naltrexone once every 3days, followed by random pretreatments of 0, 0.3,
1, or 3mg/kg morphine once every 3days. Economic demand functions were fit to
each rat's cocaine consumption from each pretreatment, and appropriate
mathematical parameters were extracted and analyzed. RESULTS: Naltrexone
decreased the essential value of cocaine in IC rats only. However, morphine
decreased the essential value of cocaine and the consumption of cocaine at zero
price in both EC and IC rats. CONCLUSION: These results indicate that
environmental experiences during development should be considered when
determining the efficacy of opioid drugs, especially for the treatment of
substance abuse.
PMID- 27511894
TI - Alisporivir Has Limited Antiviral Effects Against Ebola Virus Strains Makona and
Mayinga.
AB - Antiviral therapeutics with existing clinical safety profiles would be highly
desirable in an outbreak situation, such as the 2013-2016 emergence of Ebola
virus (EBOV) in West Africa. Although, the World Health Organization declared the
end of the outbreak early 2016, sporadic cases of EBOV infection have since been
reported. Alisporivir is the most clinically advanced broad-spectrum antiviral
that functions by targeting a host protein, cyclophilin A (CypA). A modest
antiviral effect of alisporivir against contemporary (Makona) but not historical
(Mayinga) EBOV strains was observed in tissue culture. However, this effect was
not comparable to observations for an alisporivir-susceptible virus, the
flavivirus tick-borne encephalitis virus. Thus, EBOV does not depend on (CypA)
for replication, in contrast to many other viruses pathogenic to humans.
PMID- 27511895
TI - FAM134B, the Selective Autophagy Receptor for Endoplasmic Reticulum Turnover,
Inhibits Replication of Ebola Virus Strains Makona and Mayinga.
AB - Selective autophagy of the endoplasmic reticulum (termed ER-phagy) is controlled
by members of the FAM134 reticulon protein family. Here we used mouse embryonic
fibroblasts from mice deficient in FAM134B to examine the role of the ER in
replication of historic (Mayinga) or contemporary (Makona GCO7) strains of Ebola
virus (EBOV). Loss of FAM134B resulted in 1-2 log10 higher production of
infectious EBOV, which was associated with increased production of viral proteins
GP and VP40 and greater accumulation of nucleocaspid lattices. In addition, only
10% of wild-type cells contained detectable nucleoprotein, whereas knockout of
FAM134B resulted in 80% of cells positive for nucleoprotein. Together, these data
suggest that FAM134B-dependent ER-phagy is an important limiting event in EBOV
replication in mouse cells and may have implications for further development of
antiviral therapeutics and murine models of infection.
PMID- 27511896
TI - Quadrivalent Human Papillomavirus (HPV) Vaccine Induces HPV-Specific Antibodies
in the Oral Cavity: Results From the Mid-Adult Male Vaccine Trial.
AB - BACKGROUND: Human papillomavirus virus type 16 (HPV-16) and HPV-18 cause a large
proportion of oropharyngeal cancers, which are increasing in incidence among
males, and vaccine efficacy against oral HPV infections in men has not been
previously evaluated. METHODS: Sera and saliva collected in mouthwash and Merocel
sponges at day 1 and month 7 were obtained from 150 men aged 27-45 years from
Tampa, Florida, and Cuernavaca, Mexico, who received Gardasil at day 1 and months
2 and 6. Specimens were tested for anti-HPV-16 and anti-HPV-18 immunoglobulin G
(IgG) levels by an L1 virus-like particle-based enzyme-linked immunosorbent
assay. RESULTS: All participants developed detectable serum anti-HPV-16 and anti
HPV-18 antibodies, and most had detectable antibodies in both oral specimen types
at month 7 (HPV-16 was detected in 93.2% of mouthwash specimens and 95.7% of
sponge specimens; HPV-18 was detected in 72.1% and 65.5%, respectively). Antibody
concentrations in saliva were approximately 3 logs lower than in serum. HPV-16-
and HPV-18-specific antibody levels, normalized to total IgG levels, in both oral
specimen types at month 7 were significantly correlated with serum levels (for
HPV-16, rho was 0.90 for mouthwash specimens and 0.92 for sponge specimens; for
HPV-18, rho was 0.89 and 0.86, respectively). CONCLUSIONS: This is the first
study demonstrating that vaccination of males with Gardasil induces HPV antibody
levels at the oral cavity that correlate with circulating levels.
PMID- 27511897
TI - High-Resolution Molecular Typing of Trypanosoma cruzi in 2 Large Outbreaks of
Acute Chagas Disease in Colombia.
AB - Oral transmission of Trypanosoma cruzi has gained relevance because of its
association with high morbidity and lethality rates. This transmission route is
responsible for maintaining the infection of the parasite in sylvatic cycles, and
human cases have been associated mainly with the consumption of food contaminated
with triatomine feces or didelphid secretions. Several ecological changes allow
the intrusion of sylvatic reservoirs and triatomines to the domestic environments
with subsequent food contamination. Here, high-resolution molecular tools were
used to detect and genotype T. cruzi across humans, reservoirs, and insect
vectors in 2 acute outbreaks of presumptive oral transmission in eastern
Colombia.
PMID- 27511898
TI - Identification of Giardia lamblia Assemblage E in Humans Points to a New
Anthropozoonotic Cycle.
AB - Giardia lamblia is a pathogen transmitted by water and food that causes infection
worldwide. Giardia genotypes are classified into 8 assemblages (A-H). Assemblages
A and B are detected in humans, but they are potentially zoonotic because they
infect other mammalian hosts. Giardia in samples from 44 children was genotyped.
Conserved fragments of the genes encoding beta-giardin and glutamate
dehydrogenase were sequenced and their alignment were carried out with sequences
deposited in GenBank. As expected for Rio de Janeiro, the majority of samples
were related to assemblage A. Surprisingly, assemblage E was detected in 15
samples. Detection of assemblage E in humans suggests a new zoonotic route of
Giardia transmission.
PMID- 27511900
TI - Unprecedented Catalytic Wet Oxidation of Glucose to Succinic Acid Induced by the
Addition of n-Butylamine to a Ru(III) Catalyst.
AB - A new pathway for the catalytic wet oxidation (CWO) of glucose is described.
Employing a cationic Ru@MNP catalyst, succinic acid is obtained in unprecedently
high yield (87.5 %) for a >99.9 % conversion of glucose, most probably through a
free radical mechanism combined with catalytic didehydroxylation of vicinal diols
and hydrogenation of the resulted unsaturated intermediate.
PMID- 27511899
TI - miR-155 expression and correlation with clinical outcome in pediatric AML: A
report from Children's Oncology Group.
AB - BACKGROUND: Aberrant expression of microRNA-155 (miR-155) has been implicated in
acute myeloid leukemia (AML) and associated with clinical outcome. PROCEDURE: We
evaluated miR-155 expression in 198 children with normal karyotype AML (NK-AML)
enrolled in Children's Oncology Group (COG) AML trial AAML0531 and correlated miR
155 expression levels with disease characteristics and clinical outcome. Patients
were divided into quartiles (Q1-Q4) based on miR-155 expression level, and
disease characteristics were then evaluated and correlated with miR-155
expression. RESULTS: MiR-155 expression varied over 4-log10-fold range relative
to its expression in normal marrow with a median expression level of 0.825 (range
0.043-25.630) for the entire study cohort. Increasing miR-155 expression was
highly associated with the presence of FLT3/ITD mutations (P < 0.001) and high
risk disease (P < 0.001) and inversely associated with standard-risk (P = 0.008)
and low-risk disease (P = 0.041). Patients with highest miR-155 expression had a
complete remission (CR) rate of 46% compared with 82% in low expressers (P <
0.001) with a correspondingly lower event-free (EFS) and overall survival (OS) (P
< 0.001 and P = 0.002, respectively). In a multivariate model that included
molecular risk factors, high miR-155 expression remained a significant
independent predictor of OS (P = 0.022) and EFS (0.019). CONCLUSIONS: High miR
155 expression is an adverse prognostic factor in pediatric NK-AML patients.
Specifically, high miR-155 expression not only correlates with FLT3/ITD mutation
status and high-risk disease but it is also an independent predictor of worse EFS
and OS.
PMID- 27511901
TI - The prevalence of Chlamydia trachomatis and Mycoplasma genitalium tubal
infections and their effects on the expression of IL-6 and leukaemia inhibitory
factor in Fallopian tubes with and without an ectopic pregnancy.
AB - This was a prospective case-control study that measured the prevalence of
Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium
(MG) by an IVD CE multiplex PCR kit in fresh Fallopian tubes (FT) obtained from
96 ectopic pregnancies (EP) and 61 controls in the midluteal phase of the cycle.
We later measured the expression profile of IL-6, leukaemia inhibitory factor
(LIF) and their signalling molecules, in respect to the type and number of
infections, by immunohistochemistry, ELISA and quantitative RT-PCR. The
frequencies of CT, and MG mono- and co-infections were significantly higher in
EP. IL-6, LIF, their receptors and intracellular mediators were significantly up
regulated at the gene and protein levels in positive compared with negative FTs
within each group (P < 0.05). EP tubal samples with co-infections showed the
highest significant expression of the candidate cytokines by all techniques (P <
0.05). CT and MG are frequent in EP and up-regulate the tubal expression of IL-6,
LIF and their signalling molecules. Both cytokines could be involved in the tubal
immune response against bacterial infections, as well as the pathogenesis of EP.
Further studies are needed to explore the roles of IL-6 family in infection
induced tubal inflammation and EP.
PMID- 27511902
TI - Predictive global trends in the incidence and mortality of pancreatic cancer
based on geographic location, socio-economic status, and demographic shift.
AB - BACKGROUND AND OBJECTIVES: Pancreatic Cancer (PC) is a lethal malignancy that
accounts for about 4% of cancer-related deaths worldwide. The aim of this study
is to describe the influence of geography (based on WHO regions), socio-economic
development (based on Human Development Index [HDI]) and demographic shift on the
temporal trends in global incidence and mortality of PC. METHODS: Data (2012
2030) relating to the incidence, mortality of PC and demographic shifts based on
WHO regions and HDI areas were extracted from GLOBOCAN 2012. Linear regression
was used to evaluate trends in total incidence and mortality. RESULTS: We noted a
definite association between PC and higher socio-economic status. Advanced age
(age >=65) contributed to the rising burden in all socio-economic regions of the
world except in the Low Human Development (LHD) countries where the disease
predominantly affected population <65 years of age. CONCLUSIONS: The global
burden of PC is expected to rise significantly over the next few decades
regardless of geographic location, socio-economic development, age and gender.
Advance knowledge of this data can help formulate strategies to specifically
target countries and populations that promote public health policy to tackle this
lethal disease on the global stage. J. Surg. Oncol. 2016;114:736-742. (c) 2016
Wiley Periodicals, Inc.
PMID- 27511903
TI - Golgi membrane-associated degradation pathway in yeast and mammals.
AB - Autophagy is a cellular process that degrades subcellular constituents, and is
conserved from yeast to mammals. Although autophagy is believed to be essential
for living cells, cells lacking Atg5 or Atg7 are healthy, suggesting that a non
canonical degradation pathway exists to compensate for the lack of autophagy. In
this study, we show that the budding yeast Saccharomyces cerevisiae, which lacks
Atg5, undergoes bulk protein degradation using Golgi-mediated structures to
compensate for autophagy when treated with amphotericin B1, a polyene antifungal
drug. We named this mechanism Golgi membrane-associated degradation (GOMED)
pathway. This process is driven by the disruption of PI(4)P-dependent anterograde
trafficking from the Golgi, and it also exists in Atg5-deficient mammalian cells.
Biologically, when an Atg5-deficient beta-cell line and Atg7-deficient beta-cells
were cultured in glucose-deprived medium, a disruption in the secretion of
insulin granules from the Golgi occurred, and GOMED was induced to digest these
(pro)insulin granules. In conclusion, GOMED is activated by the disruption of
PI(4)P-dependent anterograde trafficking in autophagy-deficient yeast and
mammalian cells.
PMID- 27511904
TI - Decision Aids Can Support Cancer Clinical Trials Decisions: Results of a
Randomized Trial.
AB - BACKGROUND: Cancer patients often do not make informed decisions regarding
clinical trial participation. This study evaluated whether a web-based decision
aid (DA) could support trial decisions compared with our cancer center's website.
METHODS: Adults diagnosed with cancer in the past 6 months who had not previously
participated in a cancer clinical trial were eligible. Participants were
randomized to view the DA or our cancer center's website (enhanced usual care
[UC]). Controlling for whether participants had heard of cancer clinical trials
and educational attainment, multivariable linear regression examined group on
knowledge, self-efficacy for finding trial information, decisional conflict
(values clarity and uncertainty), intent to participate, decision readiness, and
trial perceptions. RESULTS: Two hundred patients (86%) consented between May 2014
and April 2015. One hundred were randomized to each group. Surveys were completed
by 87 in the DA group and 90 in the UC group. DA group participants reported
clearer values regarding trial participation than UC group participants reported
(least squares [LS] mean = 15.8 vs. 32, p < .0001) and less uncertainty (LS mean
= 24.3 vs. 36.4, p = .025). The DA group had higher objective knowledge than the
UC group's (LS mean = 69.8 vs. 55.8, p < .0001). There were no differences
between groups in intent to participate. CONCLUSIONS: Improvements on key
decision outcomes including knowledge, self-efficacy, certainty about choice, and
values clarity among participants who viewed the DA suggest web-based DAs can
support informed decisions about trial participation among cancer patients facing
this preference-sensitive choice. Although better informing patients before trial
participation could improve retention, more work is needed to examine DA impact
on enrollment and retention. IMPLICATIONS FOR PRACTICE: This paper describes
evidence regarding a decision tool to support patients' decisions about trial
participation. By improving knowledge, helping patients clarify preferences for
participation, and facilitating conversations about trials, decision aids could
lead to decisions about participation that better match patients' preferences,
promoting patient-centered care and the ethical conduct of clinical research.
PMID- 27511905
TI - Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse
Events in Patients With Advanced Basal Cell Carcinoma.
AB - : Abnormal activation of hedgehog pathway signaling is a key driver in the
pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small
molecule inhibitor of hedgehog pathway signaling, is approved by regulatory
authorities for the treatment of adults who have metastatic BCC or locally
advanced BCC that has recurred after surgery, or who are not candidates for
surgery and who are not candidates for radiation. A second inhibitor, sonidegib,
was also recently approved for the same patient group with locally advanced BCC.
Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)
treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss,
and asthenia (fatigue). These AEs are thought to be mechanistically related to
inhibition of the hedgehog pathway in normal tissue. Although the severity of the
majority of AEs associated with HPIs is grade 1-2, the long-term nature of these
AEs can lead to decreased quality of life, treatment interruption, and in some
cases discontinuation, all of which might affect clinical outcome. The incidence,
clinical presentation, putative mechanisms, and management strategies for AEs
related to HPIs in advanced BCC are described. These observations represent the
first step toward the development of mechanism-based preventive and management
strategies. Knowledge of these AEs will allow health care professionals to
provide appropriate counseling and supportive care interventions, all of which
will contribute to improved quality of life and optimal benefit from therapy.
IMPLICATIONS FOR PRACTICE: The hedgehog pathway inhibitors (HPIs) vismodegib and
sonidegib represent a therapeutic breakthrough for patients with advanced basal
cell carcinoma. However, the nature of the low-grade adverse events (AEs)
commonly observed in HPI-treated patients, including muscle spasms,
ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical
outcomes as a result of decreased quality of life and treatment discontinuation.
The incidence, clinical presentation, putative mechanisms, and management
strategies for AEs related to administration of HPIs are described, with the goal
of enabling health care professionals to provide appropriate counseling and
supportive care interventions to their patients.
PMID- 27511906
TI - Acupuncture for Chemoradiation Therapy-Related Dysphagia in Head and Neck Cancer:
A Pilot Randomized Sham-Controlled Trial.
AB - INTRODUCTION: Dysphagia is common in head and neck cancer patients after
concurrent chemoradiation therapy (CRT). This study evaluated the feasibility of
conducting a randomized sham-controlled trial and collected preliminary data on
safety and efficacy of acupuncture. PATIENTS AND METHODS: Head and neck cancer
(HNC) patients with stage III-IV squamous cell carcinoma were randomized to 12
sessions of either active acupuncture (AA) or sham acupuncture (SA) during and
following CRT. Patients were blinded to treatment assignment. Swallowing-related
quality of life (QOL) was assessed using the MD Anderson Dysphagia Inventory
(MDADI) total and subscale scores. RESULTS: Multiple aspects of trial feasibility
were confirmed. Forty-two of 196 patients screened (21%) were enrolled and
randomized to receive AA (n = 21) or SA (n = 21); 79% completed at least 10 of 12
planned acupuncture sessions; 81% completed the study follow-ups. The majority of
patients reported uncertainty regarding their treatment assignment, with no
difference between the AA and SA groups. Audits confirmed both AA and SA
treatments were delivered with high fidelity. No serious acupuncture-related side
effects were observed. MDADI total scores significantly improved from baseline to
12 months post-CRT in both groups (AA: +7.9; SA +13.9; p = .044, p < .001).
Similar patterns were observed for the MDADI global subscale (AA: +25.0; SA
+22.7; p = .001, p = .002). Intent-to-treat analyses suggested no difference
between the treatment groups (p = .17, p = .76 for MDADI total and global scores,
respectively). CONCLUSION: A sham-controlled randomized trial evaluating
acupuncture in dysphagia-related QOL in HNC found the procedure to be feasible
and safe. Further investigation is required to evaluate efficacy. IMPLICATIONS
FOR PRACTICE: Dysphagia or swallowing difficulty is an important and common
condition after concurrent chemoradiation therapy in head and neck cancer
patients. In addition to current available supportive care, acupuncture may offer
potential for treating dysphagia. This study demonstrated that both active
acupuncture and sham acupuncture are safe and were associated with improved
dysphagia-related quality of life from baseline to 12 months after concurrent
chemoradiation therapy. This study was not designed to inform underlying specific
versus nonspecific effects. Future larger-scale pragmatic clinical trials
evaluating the effectiveness of acupuncture versus standard of care are
warranted, and further mechanistic research is needed to understand how active
versus purportedly sham acupuncture procedures affect dysphagia-related symptoms.
PMID- 27511908
TI - Increased Risk of Autism Development in Children Whose Mothers Experienced Birth
Complications or Received Labor and Delivery Drugs.
AB - Autism spectrum disorder (ASD) is a perplexing and pervasive developmental
disorder characterized by social difficulties, communicative deficits, and
repetitive behavior. The increased rate of ASD diagnosis has raised questions
concerning the genetic and environmental factors contributing to the development
of this disorder; meanwhile, the cause of ASD remains unknown. This study
surveyed mothers of ASD and non-ASD children to determine possible effects of
labor and delivery (L&D) drugs on the development of ASD. The survey was
administered to mothers; however, the results were analyzed by child, as the
study focused on the development of autism. Furthermore, an independent ASD
dataset from the Southwest Autism Research and Resource Center was analyzed and
compared. Indeed, L&D drugs are associated with ASD (p = .039). Moreover, the
Southwest Autism Research and Resource Center dataset shows that the labor
induction drug, Pitocin, is significantly associated with ASD (p = .004). We also
observed a synergistic effect between administrations of L&D drugs and
experiencing a birth complication, in which both obstetrics factors occurring
together increased the likelihood of the fetus developing ASD later in life (p =
.0003). The present study shows the possible effects of L&D drugs, such as
Pitocin labor-inducing and analgesic drugs, on children and ASD.
PMID- 27511907
TI - Repairing the Brain by SCF+G-CSF Treatment at 6 Months Postexperimental Stroke:
Mechanistic Determination of the Causal Link Between Neurovascular Regeneration
and Motor Functional Recovery.
AB - Stroke, a leading cause of adult disability in the world, is a severe medical
condition with limited treatment. Physical therapy, the only treatment available
for stroke rehabilitation, appears to be effective within 6 months post-stroke.
Here, we have mechanistically determined the efficacy of combined two
hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony
stimulating factor (G-CSF; SCF + G-CSF), in brain repair 6 months after cortical
infarct induction in the transgenic mice carrying yellow fluorescent protein in
Layer V pyramidal neurons (Thy1-YFP-H). Using a combination of live brain
imaging, whole brain imaging, molecular manipulation, synaptic and vascular
assessments, and motor function examination, we found that SCF + G-CSF promoted
mushroom spine formation, enlarged postsynaptic membrane size, and increased
postsynaptic density-95 accumulation and blood vessel density in the peri-infarct
cavity cortex; and that SCF + G-CSF treatment improved motor functional recovery.
The SCF + G-CSF-enhanced motor functional recovery was dependent on the synaptic
and vascular regeneration in the peri-infarct cavity cortex. These data suggest
that a stroke-damaged brain is repairable by SCF + G-CSF even 6 months after the
lesion occurs. This study provides novel insights into the development of new
restorative strategies for stroke recovery.
PMID- 27511910
TI - Extramammary Paget disease of the perianal region: the potential role of
imiquimod in achieving disease control.
AB - Extramammary Paget disease (EMPD) is a rare perineal neoplasia associated with a
high rate of local recurrence. Surgical excision is the standard treatment;
however, this has high rates of post-operative morbidity in combination with
potentially mutilating results. Previous literature has demonstrated good
response with imiquimod 5% cream in patients with vulval EMPD, yet its
effectiveness in primary perianal disease is unknown.We describe the case of a 40
year-old woman presenting with EMPD of the perianal region, providing detailed
histological and pictoral evidence of its response to topical imiquimod 5% cream
over a 16-week period, which initially resulted in remission prior to metastatic
lymph node recurrence. This case demonstrates the potential for topical imiquimod
cream to avoid major surgery and its associated complications in patients
presenting with EMPD of the perianal region. We discuss the current evidence for
treating this rare condition with medical therapy, how this case adds to current
literature and possible future directions.
PMID- 27511909
TI - Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce
Oxidative Stress in Bystander Neural Stem Progenitors.
AB - Harmful effects that alter the homeostasis of neural stem or progenitor cells
(NSPs) can affect regenerative processes in the central nervous system. We
investigated the effect of soluble factors secreted by control or (137)Cs-gamma
irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in
recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor
cells, following 24 h of growth, induced prominent oxidative stress in recipient
NSPs as judged by overall increases in mitochondrial superoxide radical levels (p
< .001), activation of c-jun N-terminal kinase, and decrease in the active form
of FoxO3a. The induced oxidative stress was associated with phosphorylation of
p53 on serine 15, a marker of DNA damage, induction of the cyclin-cyclin
dependent kinase inhibitors p21(Waf1) and p27(Kip1), and perturbations in cell
cycle progression (p < .001). These changes were also associated with increased
apoptosis as determined by enhanced annexin V staining (p < .001) and caspase 8
activation (p < .05) and altered expression of critical regulators of self
renewal, proliferation, and differentiation. Exposure of the tumor cells to
radiation only slightly altered the induced oxidative changes in the bystander
NSPs, except for medium from irradiated medulloblastoma cells that was more
potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p
< .001). The elucidation of such stressful bystander effects provides avenues to
understand the biochemical events underlying the development or exacerbation of
degenerative outcomes associated with brain cancers. It is also relevant to
tissue culture protocols whereby growth medium conditioned by tumor cells is
often used to support the growth of stem cells.
PMID- 27511911
TI - 21st century twist on Cullen's sign: new generation anticoagulants and splenic
traum.
AB - New anticoagulants such as Rivaroxaban have become a popular choice for patients
needing anticoagulation for atrial fibrillation or venous thromboembolism,
chiefly because anticoagulation is maintained without the need for monitoring.
This can be problematic in cases of trauma, and in this article, we discuss the
management and outcome of managing an elderly patient with a shattered spleen
while on Rivaroxaban.
PMID- 27511912
TI - Peribiliary hepatic cysts presenting as hilar cholangiocarcinoma in a patient
with end-stage liver disease.
AB - Peribiliary cysts are cystic dilatations of peribiliary glands in the liver. They
are present in ~50% of cirrhotic patients, but are underrecognized because they
are usually asymptomatic and rarely present as obstructive jaundice. A 63-year
old male with hepatitis C cirrhosis, awaiting liver transplantation, had a new
finding of intrahepatic dilatation on magnetic resonance imaging. This was
initially concerning for cholangiocarcinoma, but was ultimately diagnosed as
peribiliary cysts. Peribiliary cysts can imitate cholangiocarcinoma on imaging.
Therefore, awareness of this condition is essential because misdiagnosis may lead
to inappropriate delay or denial for liver transplantation. The ideal imaging
modalities to identify peribiliary cysts are magnetic resonance cholangiography
and drip infusion cholangiographic computed tomography, though hepatic
dysfunction may limit the usefulness of the latter. Peribiliary cysts should be
considered in cirrhotic patients with cholestasis, biliary dilatations and
negative biopsy of the biliary system for malignancy.
PMID- 27511913
TI - Hepatocyte-protective effect of nectandrin B, a nutmeg lignan, against oxidative
stress: Role of Nrf2 activation through ERK phosphorylation and AMPK-dependent
inhibition of GSK-3beta.
AB - Oxidative stress can contribute to the development and progression of liver
diseases, such as drug-induced or alcoholic liver injury, nonalcoholic fatty
liver disease, and nonalcoholic steatohepatitis. Nectandrin B is a bioactive
lignan isolated from nutmeg extract. To date, little information is available
about its pharmacological activities in the liver. This study investigated the
hepatocyte-protective effect of nectandrin B against tert-butylhydroperoxide
induced oxidative injury and the underlying molecular mechanism. The cell
viability assay revealed that nectandrin B prevents apoptosis stimulated by tert
butylhydroperoxide in both HepG2 cells and primary mouse hepatocytes. Nectandrin
B also attenuated ROS production and restored the depleted glutathione level.
Real-time PCR and immunoblot analyses showed that the expression of glutamate
cysteine ligase, an enzyme responsible for the glutathione biosynthesis, was
induced by nectandrin B, indicating its indirect antioxidative effect. The NF-E2
related factor-2 (Nrf2) regulates gene expression of an array of antioxidant
enzymes in hepatocytes. Nectandrin B stimulated Nrf2 activation as evidenced by
its enhanced nuclear accumulation and increased antioxidant response element
(ARE)-luciferase activity. Intriguingly, the hepatocyte-protective effect of
nectandrin B against oxidative damage was completely abrogated by Nrf2 knockdown
using Nrf2 specific siRNA. Nectandrin B promoted ERK activation, but inactivated
GSK-3beta through the AMPK-mediated inhibitory phosphorylation. The enforced
overexpression of dominant-negative mutant of MEK1 or AMPKalpha, or wild-type GSK
3beta inhibited the increase in the NQO1-ARE-luciferase activity stimulated by
nectandrin B, suggesting that both ERK and AMPK-GSK-3beta signalings are involved
in the activation of Nrf2/ARE pathway by nectandrin B. Consistent with this,
cytoprotection and restoration of glutathione level by nectandrin B was also
blocked by the overexpression of dominant-negative MEK1 or wild-type GSK-3beta.
Finally, our data demonstrate that nectandrin B has the ability to protect
hepatocytes against oxidative injury through the activation of Nrf2/ARE pathway
mediated by ERK phosphorylation and AMPK-dependent inactivation of GSK-3beta.
PMID- 27511914
TI - A computer-aided system for automatic extraction of femur neck trabecular bone
architecture using isotropic volume construction from clinical hip computed
tomography images.
AB - Hip fractures due to osteoporosis are increasing progressively across the globe.
It is also difficult for those fractured patients to undergo dual-energy X-ray
absorptiometry scans due to its complicated protocol and its associated cost. The
utilisation of computed tomography for the fracture treatment has become common
in the clinical practice. It would be helpful for orthopaedic clinicians, if they
could get some additional information related to bone strength for better
treatment planning. The aim of our study was to develop an automated system to
segment the femoral neck region, extract the cortical and trabecular bone
parameters, and assess the bone strength using an isotropic volume construction
from clinical computed tomography images. The right hip computed tomography and
right femur dual-energy X-ray absorptiometry measurements were taken from 50
south-Indian females aged 30-80 years. Each computed tomography image volume was
re-constructed to form isotropic volumes. An automated system by incorporating
active contour models was used to segment the neck region. A minimum distance
boundary method was applied to isolate the cortical and trabecular bone
components. The trabecular bone was enhanced and segmented using trabecular
enrichment approach. The cortical and trabecular bone features were extracted and
statistically compared with dual-energy X-ray absorptiometry measured femur neck
bone mineral density. The extracted bone measures demonstrated a significant
correlation with neck bone mineral density (r > 0.7, p < 0.001). The inclusion of
cortical measures, along with the trabecular measures extracted after isotropic
volume construction and trabecular enrichment approach procedures, resulted in
better estimation of bone strength. The findings suggest that the proposed system
using the clinical computed tomography images scanned with low dose could
eventually be helpful in osteoporosis diagnosis and its treatment planning.
PMID- 27511915
TI - Royal London space analysis: plaster versus digital model assessment.
AB - Aim: With the advent of digital study models, the importance of being able to
evaluate space requirements becomes valuable to treatment planning and the
justification for any required extraction pattern. This study was undertaken to
compare the validity and reliability of the Royal London space analysis (RLSA)
undertaken on plaster as compared with digital models. Materials and methods: A
pilot study (n = 5) was undertaken on plaster and digital models to evaluate the
feasibility of digital space planning. This also helped to determine the sample
size calculation and as a result, 30 sets of study models with specified
inclusion criteria were selected. All five components of the RLSA, namely:
crowding; depth of occlusal curve; arch expansion/contraction; incisor antero
posterior advancement and inclination (assessed from the pre-treatment lateral
cephalogram) were accounted for in relation to both model types. The plaster
models served as the gold standard. Intra-operator measurement error
(reliability) was evaluated along with a direct comparison of the measured
digital values (validity) with the plaster models. Results: The measurement error
or coefficient of repeatability was comparable for plaster and digital space
analyses and ranged from 0.66 to 0.95mm. No difference was found between the
space analysis performed in either the upper or lower dental arch. Hence, the
null hypothesis was accepted. The digital model measurements were consistently
larger, albeit by a relatively small amount, than the plaster models (0.35mm
upper arch and 0.32mm lower arch). Conclusion: No difference was detected in the
RLSA when performed using either plaster or digital models. Thus, digital space
analysis provides a valid and reproducible alternative method in the new era of
digital records.
PMID- 27511917
TI - Science and Culture: Modern "cathedral" offers artistic inspiration.
PMID- 27511918
TI - Inner Workings: Spotting gravitational waves using pulsar ticks.
PMID- 27511920
TI - Atomic structure of a rhinovirus C, a virus species linked to severe childhood
asthma.
AB - Isolates of rhinovirus C (RV-C), a recently identified Enterovirus (EV) species,
are the causative agents of severe respiratory infections among children and are
linked to childhood asthma exacerbations. The RV-C have been refractory to
structure determination because they are difficult to propagate in vitro. Here,
we report the cryo-EM atomic structures of the full virion and native empty
particle (NEP) of RV-C15a. The virus has 60 "fingers" on the virus outer surface
that probably function as dominant immunogens. Because the NEPs also display
these fingers, they may have utility as vaccine candidates. A sequence-conserved
surface depression adjacent to each finger forms a likely binding site for the
sialic acid on its receptor. The RV-C, unlike other EVs, are resistant to capsid
binding antiviral compounds because the hydrophobic pocket in VP1 is filled with
multiple bulky residues. These results define potential molecular determinants
for designing antiviral therapeutics and vaccines.
PMID- 27511921
TI - A Secondary Analysis of Sleep Quality Changes in Older Adults From a Randomized
Trial of an MBSR Program.
AB - This secondary analysis examined changes in sleep quality associated with
participation in a Mindfulness-Based Stress Reduction (MBSR) program among
healthy older adults. Data were collected at baseline, 8-weeks post-treatment,
and a 6-month follow-up from adults aged >= 65 ( N = 200), randomly assigned to
MBSR or a waitlist control. Group differences were examined using mixed analysis
of covariance with repeated measures on the total Pittsburgh Sleep Quality Index
(PSQI) score. A small-sized, significant effect was found on overall sleep among
MBSR participants with baseline PSQI scores > 5, indicative of a sleep
disturbance, F(2, 80) = 4.32, p = .02, etap2 = .05. A medium-sized, significant
effect was found for MBSR participants with baseline PSQI scores >= 10, F(2, 28)
= 3.13, p = .04, etap2 = .10. These findings indicate that improved sleep quality
for older adults who have higher levels of sleep disturbance may be associated
with participation in MBSR.
PMID- 27511922
TI - Enhancing and Maintaining Memory in Older Adulthood.
PMID- 27511923
TI - The Efficiency of Sensory Integration Interventions in Preterm Infants.
AB - This study aimed to explore the effects of individualized sensory integration
interventions on the sensory processing functions of preterm infants. Thirty-four
preterm infants (intervention group) at a corrected age of seven months and 34
term infants (control group) were included. The preterm infants underwent an
eight-week sensory integration intervention. Before and after the intervention,
the preterm infants' sensory processing functions were evaluated using the Test
of Sensory Functions in Infants and compared with those of term infants. Preterm
infants had significantly poorer sensory processing function preintervention when
compared with term infants. There was a significant improvement in preterm
infants' sensory processing functions after the sensory integration intervention.
In conclusion, preterm infants should be evaluated for sensory processing
disorders and individualized sensory integration interventions should be
implemented.
PMID- 27511924
TI - Pancreatic ductal adenocarcinoma in BRCA2 mutation carriers.
AB - Germline BRCA2 mutations are the first known cause of inherited (familial)
pancreatic ductal adenocarcinoma (PDAC). This tumor is the third most frequent
cancer in carriers of germline BRCA2 mutations, as it occurs in around 10% of
BRCA2 families. PDAC is known as one of the most highly lethal cancers, mainly
because of its chemoresistance and frequently late diagnosis. Based on recent
developments in molecular biology, a subgroup of BRCA2-associated PDAC has been
created, allowing screening, early surgical treatment and personalized systemic
treatment. BRCA2 germline mutation carriers who have >=1 first-degree relative,
or >=2 blood relatives with PDAC, should undergo screening and regular follow-up
based on magnetic resonance imaging and endoscopic ultrasound. The goal of
screening is to detect early invasive PDAC and advanced precancerous lesions
suitable for a stepwise surgical complete (R0) resection. Increasing evidence on
the molecular role of the BRCA2 protein in the homologous recombination of DNA
damages suggest that BRCA2-related PDAC are sensitive to agents causing DNA cross
linking damage, such as platinum salts, and treatments targeting rescue DNA
repair pathways, such as poly(ADP-ribose) polymerase inhibitors that are
currently under investigation.
PMID- 27511925
TI - Shifts in Rumen Fermentation and Microbiota Are Associated with Dissolved Ruminal
Hydrogen Concentrations in Lactating Dairy Cows Fed Different Types of
Carbohydrates.
AB - BACKGROUND: Different carbohydrates ingested greatly influence rumen fermentation
and microbiota and gaseous methane emissions. Dissolved hydrogen concentration is
related to rumen fermentation and methane production. OBJECTIVES: We tested the
hypothesis that carbohydrates ingested greatly alter the rumen environment in
dairy cows, and that dissolved hydrogen concentration is associated with these
changes in rumen fermentation and microbiota. METHODS: Twenty-eight lactating
Chinese Holstein dairy cows [aged 4-5 y, body weight 480 +/- 37 kg (mean +/- SD)]
were used in a randomized complete block design to investigate effects of 4 diets
differing in forage content (45% compared with 35%) and source (rice straw
compared with a mixture of rice straw and corn silage) on feed intake, rumen
fermentation, and microbial populations. RESULTS: Feed intake (10.7-12.6 kg/d)
and fiber degradation (0.584-0.692) greatly differed (P <= 0.05) between cows fed
the 4 diets, leading to large differences (P <= 0.05) in gaseous methane yield
(27.2-37.3 g/kg organic matter digested), dissolved hydrogen (0.258-1.64
MUmol/L), rumen fermentation products, and microbiota. Ruminal dissolved hydrogen
was negatively correlated (r < -0.40; P < 0.05) with molar proportion of acetate,
numbers of fungi, abundance of Fibrobacter succinogenes, and methane yield, but
positively correlated (r > 0.40; P < 0.05) with molar proportions of propionate
and n-butyrate, numbers of methanogens, and abundance of Selenomonas ruminantium
and Prevotella spp. Ruminal dissolved hydrogen was positively correlated (r =
0.93; P < 0.001) with Gibbs free energy changes of reactions producing greater
acetate and hydrogen, but not correlated with those reactions producing more
propionate without hydrogen. CONCLUSIONS: Changes in fermentation pathways from
acetate toward propionate production and in microbiota from fibrolytic toward
amylolytic species were closely associated with ruminal dissolved hydrogen in
lactating dairy cows. An unresolved paradox was that greater dissolved hydrogen
was associated with greater numbers of methanogens but with lower gaseous methane
emissions.
PMID- 27511926
TI - Plasma Concentrations of Ferritin in Early Pregnancy Are Associated with Risk of
Gestational Diabetes Mellitus in Women in the Danish National Birth Cohort.
AB - BACKGROUND: Evidence from experimental studies has demonstrated that higher than
normal iron concentrations can lead to pancreatic beta cell dysfunction and
impaired glucose metabolism. Studies on body iron stores in early pregnancy and
subsequent gestational diabetes mellitus (GDM) risk are sparse. OBJECTIVE: Our
objective was to determine whether biomarkers of body iron stores measured in
early pregnancy are associated with GDM risk. METHODS: A case-control study of
350 GDM cases and 349 non-GDM controls was conducted in participants from the
Danish National Birth Cohort. Blood was collected at a mean +/- SD gestational
age of 9.4 +/- 3.2 wk. Plasma biomarkers of iron stores, including ferritin and
soluble transferrin receptor (sTfR), were measured. Logistic regression was used
to estimate the OR of GDM associated with quintiles of plasma biomarkers of body
iron stores, controlling for maternal age, family history of diabetes, exercise
in pregnancy, parity, and prepregnancy body mass index (BMI). RESULTS: Cases were
older (mean +/- SD age: 32.2 +/- 4.3 compared with 29.9 +/- 4.2 y) and had a
higher BMI (in kg/m(2); mean +/- SD: 28.7 +/- 6.0 compared with 24.1 +/- 4.6)
than controls. Plasma concentrations of both ferritin and sTfR in early pregnancy
were significantly higher in GDM cases than in controls [means +/- SDs: 80.6 +/-
56.0 compared with 71.8 +/- 50.1 MUg/L (P = 0.03) and 1.5 +/- 0.7 compared with
1.4 +/- 0.6 mg/L (P = 0.002) for ferritin and sTfR, respectively]. Ferritin was
positively and significantly associated with GDM risk even after adjustment for
major risk factors of GDM, including prepregnancy BMI. ORs across increasing
quintiles of ferritin were 1.00 (reference), 1.25 (95% CI: 0.70, 2.22), 1.89 (95%
CI: 1.06, 3.37), 0.82 (95% CI: 0.46, 1.48), and 2.34 (95% CI: 1.30, 4.21) (P
linear trend = 0.02). CONCLUSION: These findings suggest that plasma ferritin
measured in early pregnancy is significantly and positively associated with GDM
risk.
PMID- 27511927
TI - Among 4 Diet Quality Indexes, Only the Alternate Mediterranean Diet Score Is
Associated with Better Colorectal Cancer Survival and Only in African American
Women in the Multiethnic Cohort.
AB - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related
death in the United States, with a 5-y survival rate of ~65%. Therefore, the
identification of modifiable health factors to improve CRC survival is crucial.
OBJECTIVE: We investigated the association of 4 prediagnostic a priori diet
quality indexes with CRC-specific and all-cause mortality in the Multiethnic
Cohort (MEC). METHODS: The MEC included >215,000 African-American, Native
Hawaiian, Japanese-American, Latino, and white adults living in Hawaii and
California who completed a validated quantitative food-frequency questionnaire in
1993-1996. CRC cases and deaths were identified through linkages to cancer
registries and to state and national vital registries. Sex-specific HRs and 95%
CIs were estimated for the Healthy Eating Index (HEI) 2010, the Alternative HEI
(AHEI) 2010, the alternate Mediterranean Diet (aMED) score, and the Dietary
Approaches to Stop Hypertension (DASH) index with CRC-specific and overall
mortality as the primary outcomes. Ethnicity-specific analyses were the secondary
outcomes. RESULTS: Among 4204 MEC participants diagnosed with invasive CRC
through 2010, 1976 all-cause and 1095 CRC-specific deaths were identified. A
higher aMED score was associated with lower CRC-specific mortality in women [HR
continuous pattern score divided by its respective SD (HR1SD): 0.86; 95% CI:
0.77, 0.96] but not in men (HR1SD: 1.01; 95% CI: 0.92, 1.11). A higher aMED score
was also associated with lower all-cause mortality in women (HR1SD: 0.88; 95% CI:
0.81, 0.96) but not in men (HR1SD: 1.00; 95% CI: 0.93, 1.07). The HEI-2010, AHEI
2010, and DASH index were not significantly associated with CRC-specific or with
all-cause mortality. The inverse relation for the aMED score was limited to
African Americans and to colon (compared with rectal) cancer. CONCLUSIONS: The
aMED score was related to lower mortality only in African-American women (1 of 5
ethnic groups studied). The results should be interpreted with caution due to the
small numbers of cases within ethnic groups and the issue of multiple testing.
PMID- 27511928
TI - Discretionary Foods Have a High Contribution and Fruit, Vegetables, and Legumes
Have a Low Contribution to the Total Energy Intake of the Mexican Population.
AB - BACKGROUND: Overweight and obesity prevalences in Mexico are among the highest in
the world, with dietary factors being the third-leading category of risk
contributing to the burden of disease. Consequently, studying the compliance of
the Mexican population to food-based dietary recommendations is essential for
informing nutritional policies. OBJECTIVES: We described the energy contribution
of food groups to total dietary energy intake of the Mexican population and by
sociodemographic subgroups and compared these results with Mexican dietary
recommendations. METHODS: Twenty-four-hour dietary recalls for participants aged
>=5 y (n = 7983) from the 2012 Mexican National Health and Nutrition Survey were
used. Foods and beverages were classified into 8 groups (the first 6 were called
"basic foods" and the last 2 "discretionary foods"), as follows: 1) cereals, 2)
legumes, 3) milk and dairy, 4) meat and animal products, 5) fruit and vegetables,
6) fats and oils, 7) sugar-sweetened beverages (SSBs), and 8) products high in
saturated fat and/or added sugar (HSFAS). Recommendations were based on the
Mexican Dietary Guidelines (MDG). Energy contributions from the food groups by
age, sex, region, residence (rural or urban), and socioeconomic status (SES) were
estimated. RESULTS: The highest contribution to total energy intake came from
cereals (33%) followed by HSFAS (16%), meat and animal products (14%), and SSBs
(9.8%). Fruit and vegetables (5.7%) and legumes (3.8%) had the lowest
contribution. Energy contribution of several food groups differed significantly
between population subgroups. Overall, discretionary foods contributed more than
one-quarter of total energy intake (26%) and were 13 percentage points above the
maximum allowed by the recommendations, whereas the intakes of legumes and fruit
and vegetables were much lower than recommended. CONCLUSIONS: Our results show
the need to generate a food environment conducive to a healthier diet in the
Mexican population.
PMID- 27511930
TI - The Mexican Dietary and Physical Activity Guidelines: Moving Public Nutrition
Forward in a Globalized World.
AB - The objective of this article is to explain the process of the development of and
to assess the Mexican food-based dietary and physical activity guidelines
(FBDGs). The FBDGs were developed by an intersectoral and interdisciplinary
committee of 11 national experts with input from 11 external advisors. The
sectors represented were research and academic institutions, the Ministry of
Health, and a nongovernmental organization. The evidence-based process included
the following: literature reviews of local, national, and international evidence;
review of dietary patterns of the Mexican population; key national and
international recommendations; and review of FBDGs and visual icons from other
countries. The guidelines' report follows the life-course socioecological model
rooted in a deep understanding of the epidemiology and underlying causes of
malnutrition in Mexico. The guidelines are summarized in 10 pretested main
recommendations that include, and go beyond, simply promoting the consumption of
a healthy and varied diet that includes fresh fruits, vegetables, legumes, and
whole grains and staying within caloric needs and staying active. The guidelines
strongly emphasize healthy cooking habits, enjoyable meals with family and
friends, drinking water, and avoiding the consumption of sweetened beverages,
grain-based desserts, and highly processed foods. Detailed guidelines specific to
different groups (on the basis of age and physiologic status) are also included.
An innovative aspect of the Mexican FBDGs is the inclusion of dietary guidance of
children <2 y of age. Future editions of these guidelines should consider
removing their emphasis on dietary cholesterol and total dietary fat and placing
more attention on the substitution of saturated and trans fats with healthy oils.
The process of national agenda setting, policy articulation, and implementation
of the Mexican FBDGs in the context of addressing the national obesity epidemic
deserves to be initiated and formally assessed through the lens of evidence
based, public nutrition complex adaptive systems.
PMID- 27511931
TI - Sugar-Sweetened Beverages Are the Main Sources of Added Sugar Intake in the
Mexican Population.
AB - BACKGROUND: Sugar intake has been associated with an increased prevalence of
obesity, other noncommunicable diseases, and dental caries. The WHO recommends
that free sugars should be <10% of total energy intake (TEI) and that additional
health benefits could be obtained with a reduction below 5% of TEI. OBJECTIVE:
The objective of this study was to estimate the total, intrinsic, and added sugar
intake in the Mexican diet and to identify the food groups that are the main
sources of these sugars. METHODS: We used data from a national probabilistic
survey [ENSANUT (National Health and Nutrition Survey) 2012], which represents 3
geographic regions and urban and rural areas. Dietary information was obtained by
administering a 24-h recall questionnaire to 10,096 participants. Total sugar
intake was estimated by using the National Institute of Public Health (INSP) food
composition table and an established method to estimate added sugars. RESULTS:
The mean intakes of total, intrinsic, and added sugars were 365, 127, and 238
kcal/d, respectively. Added sugars contributed 13% of TEI. Sugar-sweetened
beverages (SSBs) were the main source of sugars, contributing 69% of added
sugars. Food products high in saturated fat and/or added sugar (HSFAS) were the
second main sources of added sugars, contributing 25% of added sugars.
CONCLUSIONS: The average intake of added sugars in the Mexican diet is higher
than WHO recommendations, which may partly explain the high prevalence of obesity
and diabetes in Mexico. Because SSBs and HSFAS contribute >94% of total added
sugars, strategies to reduce their intake should be strengthened. This includes
stronger food labels to warn the consumer about the content of added sugars in
foods and beverages.
PMID- 27511932
TI - Usual Intake of Added Sugars and Saturated Fats Is High while Dietary Fiber Is
Low in the Mexican Population.
AB - BACKGROUND: The Mexican National Health and Nutrition Survey (ENSANUT) was
carried out in 2012. Information from the survey is used to design and evaluate
food and nutrition policies in Mexico. OBJECTIVE: The objective of this study was
to estimate the usual intake of energy and macronutrients in the Mexican
population by using the ENSANUT 2012. METHODS: Twenty-four-hour recall interviews
were administered to a nationally representative subsample of 10,096 individuals
aged >=1 y from the ENSANUT 2012. Usual intake distributions and the prevalence
of inadequate intakes were estimated by using the Iowa State University method.
Student's t tests and tests on the equality of proportions were used to compare
usual intakes and prevalence of inadequacy across socioeconomic status, area
(rural or urban), and region of residence (North, Center, or South). RESULTS:
Energy and macronutrient intakes and indicators of dietary adequacy are presented
for children (ages 1-4 y and 5-11 y), adolescents (12-19 y), and adults (>=20 y).
At the national level, the estimated mean fiber intake was below the Adequate
Intake for all population subgroups, suggesting inadequacies. The estimated
proportion with a usual added sugars intake of >10% of total energy intake was
>64% in all age groups. The proportion with a usual saturated fat intake of >10%
of total energy intake was estimated to be >78% in children, >66% in adolescents,
and >50% in adults. Overall, fiber intake was lower and intakes of saturated fat
and added sugars were higher in urban compared with rural areas, in the North
compared with South regions, and among those with high compared with low
socioeconomic status (P < 0.05). CONCLUSIONS: Fiber intake is lower and added
sugar and saturated fat intakes are higher than recommended for >50% of the
Mexican population aged >=1 y. These results highlight the importance of
improving the diets of the overall population to reduce the risk of
noncommunicable chronic diseases.
PMID- 27511934
TI - Intakes of Energy and Discretionary Food in Mexico Are Associated with the
Context of Eating: Mealtime, Activity, and Place.
AB - BACKGROUND: The prevalence of obesity and the intake of discretionary foods [high
saturated fat and/or added sugar (HSFAS) products and sugar-sweetened beverages
(SSBs)] are high in Mexico. It is important to understand whether the intakes of
HSFAS products and SSBs are associated with the context in which they are
consumed. OBJECTIVE: Our aim was to estimate the associations between total
energy and discretionary food (HSFAS products and SSBs) intakes and the context
of eating (mealtime, activity, and place). METHODS: We used data from 10,087
participants aged >=1 y from the Mexican National Health and Nutrition Survey
2012. Dietary intake was estimated through a 24-h dietary recall that included
questions on mealtime, activity, and place in which each food item was consumed.
The associations between energy and discretionary food intakes and the context of
eating were estimated by using multiple linear regression stratified by age group
and adjusted for sociodemographic variables. RESULTS: Compared with breakfast,
the percentage of energy that HSFAS products contributed was 16-29 (range in all
age groups) percentage points higher during midafternoon snacks and 16-23
percentage points lower at lunch and almuerzo (Mexican brunch); the percentage of
energy from SSBs was 3.4-7.6 percentage points higher during midmorning snacks (P
< 0.05). In many age groups and mealtimes, we found that compared with eating
only while seated, the percentage of energy as HSFAS was 5.3-14 percentage points
higher when watching television (P < 0.05). Compared with eating at home, the
percentage of energy from HSFAS was 12-26 percentage points higher on the street
and the percentage of energy from SSBs was 3.4-6.0 percentage points higher at
school and 2.9-15 percentage points higher at work (P < 0.05). CONCLUSIONS: These
results highlight the need to promote healthier food selection among the Mexican
population when snacking and watching television and healthier food environments
at work, school, and on the street.
PMID- 27511933
TI - Vitamin A Supplementation Increases the Uptake of Chylomicron Retinyl Esters into
the Brain of Neonatal Rats Raised under Vitamin A-Marginal Conditions.
AB - BACKGROUND: The most rapid phase of brain development occurs during the neonatal
period. Vitamin A (VA; retinol) is critical for many aspects of this process,
including neurogenesis, synaptic plasticity, learning, and memory formation.
However, the metabolism of retinol in the neonatal brain has not been extensively
explored. OBJECTIVE: We examined the uptake of VA into the brain in neonatal rats
raised under VA-marginal conditions (control group) and assessed the effect of VA
supplementation on the uptake of VA into the brain. METHODS: Sprague-Dawley
neonatal rats (n = 104) nursed by mothers fed a VA-marginal diet were randomly
assigned and treated on postnatal day 4 with an oral dose of either VA (6 MUg
retinyl palmitate/g body weight) or canola oil as the control, both of which
contained 1.8 MUCi [(3)H]retinol. Pups (n = 4/group at a time) were killed at 13
sampling times from 30 min to 24 d after dosing. The uptake of total retinol,
chylomicron-associated retinyl esters (REs), and retinol bound to retinol-binding
protein (RBP) was estimated with the use of WinSAAM version 3.0.8. RESULTS: Total
retinol mass in the brain was closely dependent on its mass in plasma over time
(r = 0.91; P < 0.001). The uptake of retinol into the brain involved both
postprandial chylomicrons and RBP, with RBP delivering most of the retinol in the
control group [0.27 nmol/d (RBP) compared with 0.01 nmol/d (chylomicrons)]. VA
supplementation increased the fractional uptake of chylomicron REs from 0.3% to
1.2% of plasma pool/d, decreased that of RBP retinol from 0.5% to 0.2% of plasma
pool/d, and increased the transfer rate of chylomicron REs from nearly zero to
0.7 nmol/d, causing a day-long elevation in the brain mass of total retinol.
CONCLUSION: Postprandial chylomicrons may be a primary mechanism for delivering a
recently ingested large dose of VA to the brain of neonatal rats raised under VA
marginal conditions.
PMID- 27511929
TI - Biomarkers of Nutrition for Development (BOND)-Vitamin A Review.
AB - The Biomarkers of Nutrition for Development (BOND) project is designed to provide
evidence-informed advice to anyone with an interest in the role of nutrition in
health. The BOND program provides information with regard to selection, use, and
interpretation of biomarkers of nutrient exposure, status, function, and effect,
which will be especially useful for readers who want to assess nutrient status.
To accomplish this objective, expert panels are recruited to evaluate the
literature and to draft comprehensive reports on the current state of the art
with regard to specific nutrient biology and available biomarkers for assessing
nutritional status at the individual and population levels. Phase I of the BOND
project includes the evaluation of biomarkers for 6 nutrients: iodine, folate,
zinc, iron, vitamin A, and vitamin B-12. This review of vitamin A is the current
article in this series. Although the vitamin was discovered >100 y ago, vitamin A
status assessment is not trivial. Serum retinol concentrations are under
homeostatic control due in part to vitamin A's use in the body for growth and
cellular differentiation and because of its toxic properties at high
concentrations. Furthermore, serum retinol concentrations are depressed during
infection and inflammation because retinol-binding protein (RBP) is a negative
acute-phase reactant, which makes status assessment challenging. Thus, this
review describes the clinical and functional indicators related to eye health and
biochemical biomarkers of vitamin A status (i.e., serum retinol, RBP, breast-milk
retinol, dose-response tests, isotope dilution methodology, and serum retinyl
esters). These biomarkers are then related to liver vitamin A concentrations,
which are usually considered the gold standard for vitamin A status. With regard
to biomarkers, future research questions and gaps in our current understanding as
well as limitations of the methods are described.
PMID- 27511935
TI - High Prevalence of Inadequate Calcium and Iron Intakes by Mexican Population
Groups as Assessed by 24-Hour Recalls.
AB - BACKGROUND: A National Health and Nutrition Survey (ENSANUT) conducted in Mexico
in 1999 identified a high prevalence of inadequate mineral intakes in the
population by using 24-h recall questionnaires. However, the 1999 survey did not
adjust for within-person variance. The 2012 ENSANUT implemented a more up-to-date
24-h recall methodology to estimate usual intake distributions and prevalence of
inadequate intakes. OBJECTIVE: We examined the distribution of usual intakes and
prevalences of inadequate intakes of calcium, iron, magnesium, and zinc in the
Mexican population in groups defined according to sex, rural or urban area,
geographic region of residence, and socioeconomic status (SES). METHODS: We used
dietary intake data obtained through the 24-h recall automated multiple-pass
method for 10,886 subjects as part of ENSANUT 2012. A second measurement on a
nonconsecutive day was obtained for 9% of the sample. Distributions of usual
intakes of the 4 minerals were obtained by using the Iowa State University
method, and the prevalence of inadequacy was estimated by using the Institute of
Medicine's Estimated Average Requirement cutoff. RESULTS: Calcium inadequacy was
25.6% in children aged 1-4 y and 54.5-88.1% in subjects >5 y old. More than 45%
of subjects >5 y old had an inadequate intake of iron. Less than 5% of children
aged <12 y and 25-35% of subjects aged >12 y had inadequate intakes of magnesium,
whereas zinc inadequacy ranged from <10% in children aged <12 y to 21.6% in men
aged >=20 y. Few differences were found between rural and urban areas, regions,
and tertiles of SES. CONCLUSIONS: Intakes of calcium, iron, magnesium, and zinc
are inadequate in the Mexican population, especially among adolescents and
adults. These results suggest a public health concern that must be addressed.
PMID- 27511936
TI - Usual Vitamin Intakes by Mexican Populations.
AB - BACKGROUND: In the past several years, the consumption of high-energy, nutrient
poor foods has increased globally. Dietary intake data collected by the National
Health and Nutrition Survey (ENSANUT) 2012 provide information to assess the
quality of the Mexican diet and to guide food and nutrition policy. OBJECTIVE:
The aim was to describe the usual intake and the prevalence of inadequate intakes
of vitamins for the overall Mexican population and by subgroups defined by sex,
age, region, urban or rural areas, and socioeconomic status (SES). METHODS:
ENSANUT 2012 is a cross-sectional probabilistic survey representative of the
Mexican population. Dietary information was collected by using the 24-h recall
automated multiple-pass method (n = 10,096) with a repeated measurement on a
subsample (n = 889) to permit adjustment for intraindividual variability with the
use of the Iowa State University method. Mean usual intakes and the prevalence of
inadequate intakes of thiamin, riboflavin, niacin, folate, and vitamins A, D, E,
C, B-6, and B-12 were calculated for children aged 1-4 y (CH1-4y), children aged
5-11 y (CH5-11y), adolescents aged 12-19 y, and adults aged >=20 y. RESULTS: In
all of the age groups, prevalences of inadequate intakes of vitamins D and E were
the highest (77-99% of adults and adolescents and 53-95% of CH5-11y and CH1-4y)
and those of folate and vitamin A were intermediate (47-70% of adults and
adolescents, 15-23% of CH5-11y and 8-13% of CH1-4y), whereas those of thiamin,
riboflavin, niacin, and vitamins B-6, B-12, and C were the lowest (0-37% of
adults, 1-27% of adolescents, and 0-2.4% of CH5-11y and CH1-4y). With few
exceptions, the highest prevalences of inadequate intakes for vitamins were
observed in the poorest populations (rural South region and the lowest tertile of
SES). CONCLUSIONS: The intake of vitamins among Mexicans is inadequate overall.
Information collected by ENSANUT can help target food assistance programs and
develop strategies to prevent vitamin deficiencies.
PMID- 27511937
TI - A Retinol Isotope Dilution Equation Predicts Both Group and Individual Total Body
Vitamin A Stores in Adults Based on Data from an Early Postdosing Blood Sample.
AB - BACKGROUND: Retinol isotope dilution (RID) is used to determine vitamin A total
body stores (TBS) after an oral dose of a vitamin A stable isotope. The generally
accepted prediction equation proposed by Olson's group in 1989 (Furr et al. Am J
Clin Nutr 1989;49:713-6) includes factors related to dose absorption and
retention, isotope equilibration in plasma compared with stores, catabolism
during the mixing period, and the optimal time for measuring plasma isotope
enrichment. OBJECTIVES: The objectives were 1) to develop a modified RID equation
and identify an earlier sampling time for predicting TBS and 2) to improve
prediction in individuals as well as groups. METHODS: To develop a modified RID
equation, we used results of model-based compartmental analysis [the Simulation,
Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org)]
of plasma [13C10]retinol kinetic data from 32 previously studied, healthy young
adults of European ancestry who had moderate vitamin A intakes and who ingested
2.95 MUmol [13C10]retinyl acetate. RESULTS: We examined the time dependence of
factors in the prediction equation related to absorption/retention (Fa) and
isotope equilibration (S) and determined that 4 or 5 d postdosing was the optimal
sampling time. TBS calculated by the equation TBS = Fa x S x (1/SAp), where SAp
is plasma retinol specific activity (fraction of dose/MUmol), were highly
correlated with model-predicted TBS (r = 0.95 and 0.96 for 4 and 5 d,
respectively; P < 0.001); predictions for individuals were also highly correlated
(Rs = 0.94 and 0.94; P < 0.001). CONCLUSION: The equation TBS ~ 0.5 * (1/SAp)
accurately predicted vitamin A TBS in this group of 32 healthy young adults and
its individual members with the use of data from 1 blood sample taken 4 d after
isotope administration.
PMID- 27511938
TI - Mexican Children under 2 Years of Age Consume Food Groups High in Energy and Low
in Micronutrients.
AB - BACKGROUND: Mexico faces malnutrition problems in the child population. Analysis
of food consumption in small children allows us to identify and propose
strategies focused on feeding to improve their nutritional status. OBJECTIVE: We
described the consumption of beverages and food groups in Mexican children <24 mo
of age. METHODS: A cross-sectional study was carried out in 926 children aged <24
mo participating in the 2012 ENSANUT (National Health and Nutrition Study).
Dietary information was obtained through 24-h recalls. The foods and beverages
consumed were divided into 17 groups. Consumption was estimated in grams or
milliliters, kilocalories per day, and percentage of energy (PE) per day. The
percentage of consumers was calculated for each food group and stratified by age
(<6, 6-11, and 12-23 mo) and by breastfeeding status (breastfed or not
breastfed). Differences in the consumption of food groups were analyzed by
breastfeeding status, area of residence (urban or rural), and socioeconomic
status (SES) by using linear regression adjusted for age, breastfeeding status,
and survey design. RESULTS: Only 35% of the children consumed breast milk. Infant
formula was consumed by 48% in children aged <6 mo and by 33% in children 6-11 mo
old. More than 35% of the children aged 6-11 and 12-23 mo and 12% of children <6
mo old consumed nondairy sugar-sweetened beverages. Legumes and seeds and maize
based preparations contributed a higher PE in rural areas (3.4% and 1.9%,
respectively) than in urban areas (11.1% and 6.4%, respectively) (P < 0.05).
Children from the lowest SES category consumed less PE from cereals other than
maize (2.4%) and more from maize-based preparations (10.2%) than did the middle
(4.9% from other cereals and 8.0% from maize) and high (6.0% from other cereals
and 4.5% from maize) SES categories (P < 0.05). CONCLUSION: Mexican children <24
mo of age do not consume a diet that meets recommendations, which is consistent
with the high prevalence of malnutrition in Mexico.
PMID- 27511939
TI - Overview of the Dietary Intakes of the Mexican Population: Results from the
National Health and Nutrition Survey 2012.
AB - BACKGROUND: Mexico is facing the double burden of malnutrition: stunting and
micronutrient deficiencies in young children, iron deficiency in pregnant women,
and widespread obesity across age groups. OBJECTIVE: The aim was to summarize and
discuss findings published in this supplement on dietary intakes and the eating
habits of the Mexican population. METHODS: A 24-h recall questionnaire that used
the multiple-pass method with a repeated measure in a fraction of the sample was
applied in a nationally representative sample. We estimated mean intakes and
percentages of inadequacy for macronutrients and micronutrients; mean intakes and
percentages of the population who adhere to dietary recommendations for food
groups; sources of added sugars; intakes of discretionary foods by mealtime,
place, and activity; and mean dietary intakes in children <2 y old. RESULTS:
Infant formula was consumed by almost half of infants aged <6 mo and sugar
sweetened beverages were consumed by two-thirds of children aged 12-23 mo. In the
different age groups, a high proportion of the population had excessive intakes
of added sugars (58-85%) and saturated fats (54-92%), whereas a high prevalence
of insufficient intakes was found for fiber (65-87%), vitamin A (8-70%), folates
(13-69%), calcium (26-88%), and iron (46-89%). Discretionary foods (nonbasic
foods high in saturated fats and/or added sugars) contributed 26% of the
population's total energy intake, whereas only 1-23% met recommendations for
legumes, seafood, fruit, vegetables, and dairy foods. CONCLUSIONS: High
proportions of Mexicans consume diets that do not meet recommendations.
Breastfeeding and complementary feeding diverged from recommendations, intakes of
discretionary foods were high, and the prevalence of nutrient inadequacies and
age groups not meeting intake recommendations of basic food groups were also
high. The results are consistent with the high prevalence of the double burden of
malnutrition and are useful to design food and nutrition policies.
PMID- 27511940
TI - Adherence to Dietary Recommendations for Food Group Intakes Is Low in the Mexican
Population.
AB - BACKGROUND: Given the high prevalence of obesity and noncommunicable diseases in
Mexico and the key role of dietary quality in these conditions, it is important
to determine Mexicans' adherence to dietary recommendations. OBJECTIVE: Our aim
was to estimate the percentage of the Mexican population who adhere to dietary
recommendations for key food groups. METHODS: We analyzed 7983 participants aged
>=5 y from the nationally representative Mexican National Health and Nutrition
Survey 2012. Dietary intake data were collected by using one 24-h recall and a
repeated 24-h recall in 9% of the sample. We used the National Cancer Institute
method for episodically consumed foods, which uses a 2-part (probability and
amount) mixed regression model to estimate the usual intake distribution and its
association with sociodemographic variables. RESULTS: For the food groups that
are encouraged, only 1-4% of the population (range across sex and age groups)
reached the recommended intake of legumes, 4-8% for seafood, 7-16% for fruit and
vegetables, and 9-23% for dairy. For food groups that are discouraged, only 10
22% did not exceed the recommended upper limit for sugar-sweetened beverages, 14
42% for high saturated fat and/or added sugar (HSFAS) products, and 9-50% for
processed meats, whereas the majority (77-93%) did not exceed the limit for red
meat. A lower proportion of adolescents than children and adults adhered to
recommendations for several food groups. Participants with higher socioeconomic
status (SES) and living in urban areas consumed more (probability of consuming
and/or amount consumed) fruit and vegetables, dairy, and HSFAS products, but they
consumed fewer legumes than those of lower SES and living in rural areas.
CONCLUSIONS: These results reveal the poor dietary quality of the Mexican
population and the urgent need to shift these habits. If current intakes
continue, the burden of disease due to obesity and noncommunicable chronic
diseases will likely remain elevated in the Mexican population.
PMID- 27511941
TI - Plasma Retinol Kinetics and beta-Carotene Bioefficacy Are Quantified by Model
Based Compartmental Analysis in Healthy Young Adults with Low Vitamin A Stores.
AB - BACKGROUND: Model-based compartmental analysis of data on plasma retinol kinetics
after administration of labeled retinol provides unique information about whole
body vitamin A metabolism. If labeled beta-carotene is coadministered, its
bioefficacy relative to the retinol reference dose can also be estimated.
OBJECTIVES: The objectives were to model plasma retinol kinetics after
administration of labeled preformed vitamin A and provitamin A beta-carotene and
to determine relative beta-carotene bioefficacy. METHODS: We used the Simulation,
Analysis and Modeling software (WinSAAM version 3.0.8; http://www.WinSAAM.org) to
analyze previously collected data on plasma [13C10]- and [13C5]retinol kinetics
for 14 d after oral administration of 1 mg [13C10]retinyl acetate and 2 mg
[13C10]beta-carotene in oil to 30 healthy young adults of European ancestry [13
men, 17 women; mean +/- SD age: 24.5 +/- 4.2 y; mean +/- SD body weight: 65.2 +/-
10 kg; mean +/- SD body mass index (in kg/m2): 22.5 +/- 1.9] with moderate
vitamin A intakes. RESULTS: A 6-component model provided the best fit to the
data, including compartments for initial metabolism of vitamin A, plasma retinol,
and extravascular vitamin A storage. The disposal rate was 6.7 +/- 3.1 MUmol/d,
fractional catabolic rate was 6.0% +/- 2.3%/d, and vitamin A stores were 123 +/-
71 MUmol. Relative beta-carotene bioefficacy, based on the ratio of the areas
under the fraction of dose curves calculated by WinSAAM, averaged 13.5% +/- 6.02%
(retinol activity equivalents = 7.7:1.0 MUg). Interindividual variation in
relative beta-carotene bioefficacy was high (CV: 44%). CONCLUSIONS: Vitamin A
kinetics in these young adults were best described by essentially the same model
that had been previously developed by using data for older adults with higher
vitamin A stores; differences in parameter values reflected differences in
vitamin A status. Estimated beta-carotene bioefficacy was relatively low but
similar to previously reported estimates obtained by graphical methods. This
trial was registered at the UK Clinical Research Network as UKCRN 7413.
PMID- 27511942
TI - From the Cover: Ethylmercury-Induced Oxidative and Endoplasmic Reticulum Stress
Mediated Autophagic Cell Death: Involvement of Autophagosome-Lysosome Fusion
Arrest.
AB - Ethylmercury (EtHg) is derived from the degradation of thimerosal, the most
widely used organomercury compound. In this study, EtHg-induced toxicity and
autophagy in the mouse kidney was observed and then the mechanism of toxicity was
explored in vitro in HK-2 cells. Low doses of EtHg induced autophagy without
causing any histopathological changes in mouse kidneys. However, mice treated
with high doses of EtHg exhibited severe focal tubular cell necrosis of the
proximal tubules with autophagy. EtHg dose-dependently increased the production
of reactive oxygen species, reduced the mitochondrial membrane potential,
activated the unfolded protein response, and increased cytosolic Ca2+ levels in
HK-2 cells. Cell death induced by EtHg exposure was caused by autophagy and
necrosis. N-acetyl cysteine and 4-phenylbutyric acid attenuated EtHg-induced
stress and ameliorated the autophagic response in HK-2 cells. Furthermore, EtHg
blocked autophagosome fusion with lysosomes, which was demonstrated via treatment
with wortmannin and chloroquine. Low doses of EtHg and rapamycin, which resulted
in minimal cytotoxicity, increased the levels of the autophagic SNARE complex
STX17 (syntaxin 17)-VAMP8-SNAP29 without altering mRNA levels, but high dose of
EtHg was cytotoxic. Inhibition of autophagic flux by chloroquin increased
autophagosome formation and necrotic cell death in HK-2 cells. Collectively, our
results show that EtHg induces autophagy via oxidative and ER stress and blockade
of autophagic flux. Autophagy might play a dual role in EtHg-induced renal
toxicity, being both protective following treatment with low doses of EtHg and
detrimental following treatment with high doses.
PMID- 27511943
TI - Effects of Capillary Microsampling on Toxicological Endpoints in Juvenile Rats.
AB - Blood sampling during juvenile rat toxicology studies is required to determine
the toxicokinetic (TK) profile of compounds. Juvenile rats are too small to
undergo repeated blood sampling using conventional methods, which collect 200-300
MUl blood at each time point. Recently, capillary microsampling (CMS) gained
interest because sample sizes are almost 10 times smaller enabling multi-sample
collection from 1 rat. Here, we evaluated the use of CMS in juvenile rats in
support of reduced animal usage. Juvenile rats at postnatal day (PND) 4, 10, and
17 underwent CMS via the submandibular, tail, and jugular veins. The CMS methods
for pups at different ages were evaluated based on sample quality and technical
practicality as well as on acute and chronic changes of toxicological parameters.
The best location for CMS was the submandibular vein for PND 4 and 10 pups and
the tail vein for PND 17 pups. No effects were found on clinical signs, body and
organ weights and biochemistry parameters when 2 * 32 MUl of blood was withdrawn
from PND 4 pups or when 3 * 32 MUl was taken from PND 10 and 17 pups within 24 h.
Significant changes in several hematology parameters were observed 24 h after CMS
due to a decrease of red blood cells and renewed production. These values had
recovered to normal 7 days after CMS. CMS is feasible in juvenile rats for TK
assessment. Utilizing this method could decrease the number of additional animals
by 75%.
PMID- 27511944
TI - Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.
AB - Efficient intercellular transfer of RNAs, proteins, and lipids as protected
exosomal cargo has been demonstrated in the CNS, but distinct physiologic and
pathologic roles have not been well defined for this pathway. The capacity to
isolate immunochemically human plasma neuron-derived exosomes (NDEs), containing
neuron-specific cargo, has permitted characterization of CNS-derived exosomes in
living humans. Constituents of the amyloid beta-peptide (Abeta)42-generating
system now are examined in 2 distinct sets of human neural cells by
quantification in astrocyte-derived exosomes (ADEs) and NDEs, enriched separately
from plasmas of patients with Alzheimer's disease (AD) or frontotemporal dementia
(FTD) and matched cognitively normal controls. ADE levels of beta-site amyloid
precursor protein-cleaving enzyme 1 (BACE-1), gamma-secretase, soluble Abeta42,
soluble amyloid precursor protein (sAPP)beta, sAPPalpha, glial-derived
neurotrophic factor (GDNF), P-T181-tau, and P-S396-tau were significantly (3- to
20-fold) higher than levels in NDEs for patients and controls. BACE-1 levels also
were a mean of 7-fold higher in ADEs than in NDEs from cultured rat type-specific
neural cells. Levels of BACE-1 and sAPPbeta were significantly higher and of GDNF
significantly lower in ADEs of patients with AD than in those of controls, but
not significantly different in patients with FTD than in controls. Abundant
proteins of the Abeta42 peptide-generating system in ADEs may sustain levels in
neurons. ADE cargo proteins may be useful for studies of mechanisms of cellular
interactions and effects of BACE-1 inhibitors in AD.-Goetzl, E. J., Mustapic, M.,
Kapogiannis, D., Eitan, E., Lobach, I. V., Goetzl, L., Schwartz, J. B., Miller,
B. L. Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer's disease.
PMID- 27511946
TI - Inferior vena cava thrombosis as a cause of haemolysis in a patient on ECMO.
AB - Haemolysis, thrombosis and haemorrhage are well-documented complications of
extracorporeal membrane oxygenation. This case report outlines an unusual case of
haemolysis, thought secondary to a large mobile thrombus in the inferior vena
cava.
PMID- 27511947
TI - Children's Experiences of Epilepsy: A Systematic Review of Qualitative Studies.
AB - CONTEXT: Epilepsy is a common and severe neurologic disease associated with
increased mortality, seizure-related injury, and adverse psychological and
quality-of-life outcomes. OBJECTIVE: To describe the perspectives of children and
adolescents with epilepsy. DATA SOURCES: Medline, Embase, PsycINFO, and CINAHL
from inception to August 2015. STUDY SELECTION: Qualitative studies on children's
experiences of epilepsy. DATA EXTRACTION: Results from primary studies. We used
thematic synthesis to analyze the findings. RESULTS: Forty-three articles
involving 951 participants aged 3 to 21 years across 21 countries were included.
We identified 6 themes: loss of bodily control (being overtaken, susceptibility
to physical harm, fragility of the brain, alertness to mortality, incapacitating
fatigue), loss of privacy (declarative disease, humiliating involuntary function,
unwanted special attention, social embarrassment of medicine-taking), inescapable
inferiority and discrimination (vulnerability to prejudice, inability to achieve
academically, consciousness of abnormality, parental shame, limiting social
freedom), therapeutic burden and futility (unattainable closure, financial
burden, overwhelming life disruption, exhaustion from trialing therapies,
insurmountable side effects, awaiting a fabled remission), navigating health care
(empowerment through information, valuing empathetic and responsive care,
unexpected necessity of transition, fragmented and inconsistent care), and
recontextualizing to regain normality (distinguishing disease from identity,
taking ownership, gaining perspective and maturity, social and spiritual
connectedness). LIMITATIONS: Non-English articles were excluded. CONCLUSIONS:
Children with epilepsy experience vulnerability, disempowerment, and
discrimination. Repeated treatment failure can raise doubt about the attainment
of remission. Addressing stigma, future independence, and fear of death may
improve the overall well-being of children with epilepsy.
PMID- 27511945
TI - Ticagrelor regulates osteoblast and osteoclast function and promotes bone
formation in vivo via an adenosine-dependent mechanism.
AB - As many as 10% of bone fractures heal poorly, and large bone defects resulting
from trauma, tumor, or infection may not heal without surgical intervention.
Activation of adenosine A2A receptors (A2ARs) stimulates bone formation.
Ticagrelor and dipyridamole inhibit platelet function by inhibiting P2Y12
receptors and platelet phosphodiesterase, respectively, but share the capacity to
inhibit cellular uptake of adenosine and thereby increase extracellular adenosine
levels. Because dipyridamole promotes bone regeneration by an A2AR-mediated
mechanism we determined whether ticagrelor could regulate the cells involved in
bone homeostasis and regeneration in a murine model and whether inhibition of
P2Y12 or indirect A2AR activation via adenosine was involved. Ticagrelor,
dipyridamole and the active metabolite of clopidogrel (CAM), an alternative P2Y12
antagonist, inhibited osteoclast differentiation and promoted osteoblast
differentiation in vitro. A2AR blockade abrogated the effects of ticagrelor and
dipyridamole on osteoclast and osteoblast differentiation whereas A2BR blockade
abrogated the effects of CAM. Ticagrelor and CAM, when applied to a 3-dimentional
printed resorbable calcium-triphosphate/hydroxyapatite scaffold implanted in a
calvarial bone defect, promoted significantly more bone regeneration than the
scaffold alone and as much bone regeneration as BMP-2, a growth factor currently
used to promote bone regeneration. These results suggest novel approaches to
targeting adenosine receptors in the promotion of bone regeneration.-Mediero, A.,
Wilder, T., Reddy, V. S. R., Cheng, Q., Tovar, N., Coelho, P. G., Witek, L.,
Whatling, C., Cronstein, B. N. Ticagrelor regulates osteoblast and osteoclast
function and promotes bone formation in vivo via an adenosine-dependent
mechanism.
PMID- 27511952
TI - Human Neuron Cultures: Micropatterning Facilitates the Long-Term Growth and
Analysis of iPSC-Derived Individual Human Neurons and Neuronal Networks (Adv.
Healthcare Mater. 15/2016).
AB - Dimitri Krainc, Milan Mrksich, and co-workers demonstrate the utility of
microcontact printing technology for culturing of human neurons in defined
patterns over extended periods of time on page 1894. This approach facilitates
studies of neuronal development, cellular trafficking, and related mechanisms
that require assessment of individual neurons and neuronal networks.
PMID- 27511948
TI - Medicaid Expenditures for Children Remaining at Home After a First Finding of
Child Maltreatment.
AB - BACKGROUND: Child maltreatment is associated with physical and mental health
problems. The objective of this study was to compare Medicaid expenditures based
on a first-time finding of child maltreatment by Child Protective Services (CPS).
METHODS: This retrospective cohort study included children aged 0 to 14 years
enrolled in Utah Medicaid between January 2007 and December 2009. The exposed
group included children enrolled in Medicaid during the month of a first-time CPS
finding of maltreatment not resulting in out-of-home placement. The unexposed
group included children enrolled in Medicaid in the same months without CPS
involvement. Quantile regression was used to describe differences in average
nonpharmacy Medicaid expenditures per child-year associated with a first-time CPS
finding of maltreatment. RESULTS: A total of 6593 exposed children and 39 181
unexposed children contributed 20 670 and 105 982 child-years to this analysis,
respectively. In adjusted quantile regression, exposed children at the 50th
percentile of health care spending had annual expenditures $78 (95% confidence
interval [CI], 65 to 90) higher than unexposed children. This difference
increased to $336 (95% CI, 283 to 389) and $1038 (95% CI, 812 to 1264) at the
75th and 90th percentiles of health care spending. Differences were higher among
older children, children with mental health diagnoses, and children with repeated
episodes of CPS involvement; differences were lower among children with severe
chronic health conditions. CONCLUSIONS: Maltreatment is associated with increased
health care expenditures, but these costs are not evenly distributed. Better
understanding of the reasons for and outcomes associated with differences in
health care costs for children with a history of maltreatment is needed.
PMID- 27511953
TI - Photothermal Gene Delivery: Stimuli-Regulated Enzymatically Degradable Smart
Graphene-Oxide-Polymer Nanocarrier Facilitating Photothermal Gene Delivery (Adv.
Healthcare Mater. 15/2016).
AB - On page 1918, Won Jong Kim and co-workers use disulfide bonding for the rational
design of graphene oxide (GO) based nanocarriers. In the lower left side,
photothermally triggered gene release is illustrated in cancer cell. Polymer
detached GOis exocytosed, and subsequently gets into the macrophage (middle
right). In the macrophage, peroxidase binds to GO, thus degrades it to small
fragments which are fluorescent.
PMID- 27511954
TI - Designed Stem Cell Aggregates: Enhanced Biological Functions of Human Mesenchymal
Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles (Adv.
Healthcare Mater. 15/2016).
AB - E-cadherin-modified poly(lactic-co-glycolic acid) (hE-cad-PLGA) microparticles
were fabricated and then mediated the 3D cell aggregates of human mesenchymal
stem cells (MSCs) on page 1949 by Jun Yang and co-workers. The hE-cad-Fc matrix
and the PLGA microparticles synergistically regulate the proliferation and
bioactive factors secretions of MSCs by activating EGFR, AKT and ERK1/2 signaling
pathways. The hE-cad-PLGA microparticles offer a novel route to expand
multipotent stem cell-based clinical applications.
PMID- 27511956
TI - Factors That Influence Self-Reported Health Changes With Caregiving.
AB - OBJECTIVE: This study examined factors associated with the self-reported change
in health status as a result of caregiving. METHOD: Multinomial logistic
regression were performed to examine the sociodemographic characteristics, care
recipients' characteristics, and caregiving experiences that affect caregivers'
perceptions of health affected by caregiving using data from 1,087 caregiver
respondents in the Caregiving in the U.S. 2015 data set. Data were collected
through an online or telephone survey of randomly selected adults in 50 states.
RESULTS: Worsened self-reported health with caregiving occurred for caregivers
aged 50 to 64, racial/ethnic minorities, those who lived within 20 min of the
care recipient's home, the presence of cognitive deficits, prolonged caregiving,
and limited availability of accessible and affordable care services. Importantly,
the feeling of choice in taking on care responsibilities was associated with an
over fourfold increase in the odds ratio (OR) of better health in response to
caregiving (OR = 4.21; confidence interval [CI] = [1.95, 9.08]; p < .001).
DISCUSSION: Results suggest that improving accessibility of social service
resources to assist caregivers in being better supported and having more choice
in caregiving responsibilities may foster a positive change in health status with
caregiving.
PMID- 27511957
TI - A Novel Exercise Initiative for Seniors to Improve Balance and Physical Function.
AB - OBJECTIVE: To investigate the feasibility, effectiveness, and short-term effects
of an exercise intervention using a novel exercise park in improving seniors'
balance, physical function, and quality of life. METHOD: Randomized controlled
trial with pre- and post-intervention design (baseline and 18-week intervention)
was used. Outcome measures included measures of balance, strength, and function,
as well as quality of life and fear of falling. MANCOVA was used to assess
differences between groups (control and exercise intervention) over time.
RESULTS: Intervention group showed significant improvement on single leg stance (
p = .02, 95% confidence interval [CI] = [-8.35, -0.549]), knee strength ( p <
.01, 95% CI = [-29.14, -5.86]), 2-min walk ( p = 0.02, 95% CI = [-19.13,
0.859]), and timed sit to stand ( p = .03, 95% CI = [-2.26, -0.143]) tests.
DISCUSSION: The exercise park program improved physical function and had high
adherence and participation rate. Such intervention has been shown to be safe and
therefore might enhance participation in exercise programs for older adults.
PMID- 27511958
TI - One-Pot Synthesis of Highly Anisotropic Five-Fold-Twinned PtCu Nanoframes Used as
a Bifunctional Electrocatalyst for Oxygen Reduction and Methanol Oxidation.
AB - Five-fold-twinned PtCu nanoframes (NFs) with nanothorns protruding from their
edges are synthesized by a facile one-pot method. Compared to commercial Pt/C
catalyst, the obtained highly anisotropic five-fold-twinned PtCu NFs show
enhanced electrocatalytic performance toward the oxygen reduction reaction and
methanol oxidation reaction under alkaline conditions.
PMID- 27511959
TI - Eha, a regulator of Edwardsiella tarda, required for resistance to oxidative
stress in macrophages.
AB - Edwardsiella tarda is distributed widely in a variety of hosts. Eha has recently
been found to be its virulence regulator. In order to explore the mechanism of
its regulation, we investigated the survival rates of wild type strain ET13, and
its eha mutant and complemented strains in RAW264.7 macrophages under light
microscopic observation as well as by counting bacterial CFUs on the plates. All
of the different strains could live within the macrophages; however, the
intracellular numbers of the wild type were significantly higher than the mutant
when the incubation time extended 4 h or 6 h (P < 0.05). Furthermore, more ROS
were produced by the mutant-infected cells, indicating that Eha may enhance
ET13's capacity to detoxify ROS. In agreement with this, we found that the mutant
exhibited more sensitivity by H2O2 disk inhibitory assay and less survival
ability with H2O2 treatment. We further demonstrated that the bacterial
antioxidant enzymes SodC and KatG were regulated by Eha with qRT-PCR and beta
galactosidase assay. Collectively, our data show Eha is required for E. tarda to
resist the oxidative stress from the macrophages.
PMID- 27511960
TI - Fast and Robust Nanocellulose Width Estimation Using Turbidimetry.
AB - The dimensions of nanocelluloses are important factors in controlling their
material properties. The present study reports a fast and robust method for
estimating the widths of individual nanocellulose particles based on the
turbidities of their water dispersions. Seven types of nanocellulose, including
short and rigid cellulose nanocrystals and long and flexible cellulose
nanofibers, are prepared via different processes. Their widths are calculated
from the respective turbidity plots of their water dispersions, based on the
theory of light scattering by thin and long particles. The turbidity-derived
widths of the seven nanocelluloses range from 2 to 10 nm, and show good
correlations with the thicknesses of nanocellulose particles spread on flat mica
surfaces determined using atomic force microscopy.
PMID- 27511961
TI - A review of the ecosystem functions in oil palm plantations, using forests as a
reference system.
AB - Oil palm plantations have expanded rapidly in recent decades. This large-scale
land-use change has had great ecological, economic, and social impacts on both
the areas converted to oil palm and their surroundings. However, research on the
impacts of oil palm cultivation is scattered and patchy, and no clear overview
exists. We address this gap through a systematic and comprehensive literature
review of all ecosystem functions in oil palm plantations, including several
(genetic, medicinal and ornamental resources, information functions) not included
in previous systematic reviews. We compare ecosystem functions in oil palm
plantations to those in forests, as the conversion of forest to oil palm is
prevalent in the tropics. We find that oil palm plantations generally have
reduced ecosystem functioning compared to forests: 11 out of 14 ecosystem
functions show a net decrease in level of function. Some functions show decreases
with potentially irreversible global impacts (e.g. reductions in gas and climate
regulation, habitat and nursery functions, genetic resources, medicinal
resources, and information functions). The most serious impacts occur when forest
is cleared to establish new plantations, and immediately afterwards, especially
on peat soils. To variable degrees, specific plantation management measures can
prevent or reduce losses of some ecosystem functions (e.g. avoid illegal land
clearing via fire, avoid draining of peat, use of integrated pest management, use
of cover crops, mulch, and compost) and we highlight synergistic mitigation
measures that can improve multiple ecosystem functions simultaneously. The only
ecosystem function which increases in oil palm plantations is, unsurprisingly,
the production of marketable goods. Our review highlights numerous research gaps.
In particular, there are significant gaps with respect to socio-cultural
information functions. Further, there is a need for more empirical data on the
importance of spatial and temporal scales, such as differences among plantations
in different environments, of different sizes, and of different ages, as our
review has identified examples where ecosystem functions vary spatially and
temporally. Finally, more research is needed on developing management practices
that can offset the losses of ecosystem functions. Our findings should stimulate
research to address the identified gaps, and provide a foundation for more
systematic research and discussion on ways to minimize the negative impacts and
maximize the positive impacts of oil palm cultivation.
PMID- 27511962
TI - Optimizing electrical impedance myography of the tongue in amyotrophic lateral
sclerosis.
AB - INTRODUCTION: Electrical impedance myography (EIM) can quantify muscle health at
a range of frequencies, including that most commonly employed, 50 kHz. However,
disease-related changes in EIM data suggest the distinction between normal and
patient EIM values could be more apparent at frequencies of >50 kHz. We
investigated at what other selected frequencies tongue EIM may differentiate
healthy individuals and amyotrophic lateral sclerosis (ALS) patients, remain
reliable, and correlate with a standard metric of bulbar function. METHODS:
Tongue EIM phase data from 30 volunteers and 11 ALS patients were analyzed at 6
discrete frequencies from 50 to 500 kHz. RESULTS: Of the frequencies assessed,
EIM demonstrated maximal separation and reliability at 100 kHz, where phase value
was also significantly correlated with the bulbar subscore on the revised version
of the ALS Functional Rating Scale. CONCLUSIONS: One hundred kilohertz could
serve as an optimal frequency at which to measure EIM phase values of the tongue
in ALS. Muscle Nerve 55: 539-543, 2017.
PMID- 27511963
TI - Establishing estrogen-responsive mouse mammary organoids from single Lgr5+ cells.
AB - Recent evidence suggests that mammary cells expressing R-spondin receptor and Wnt
pathway regulator Lgr5, regarded as a stem cell marker in multiple tissues, might
represent mammary stem cells (MaSCs). Whether L gr5 marks a multipotent
subpopulation of Lin-CD24low/medCD49fhigh MaSCs remains controversial. To some
extent the differing results reflect different assays used to assess properties
of stemness, including lineage tracing in vivo, mammosphere culture, and mammary
fat pad transplantation assays. To address this issue directly, we isolated Lgr5+
cells from mammary glands of Lgr5-lacZ mice and established organoids based on
principles adapted from studies of Wnt-driven Lgr5+ cell populations in other
organs. Mammary organoids were grown from single Lgr5+ mammary cells in Matrigel,
the substratum of choice for intestinal organoids, and in a growth factor
cocktail containing EGF, Wnt3a and R-spondin, designed to optimally activate the
endogenous Wnt signaling program of stem cells. Colonies derived from single
Lgr5+ cells manifest at least four distinct cell populations: Lgr5+ and Lgr5-
basal cells and c-Kit+ and c-Kit- luminal cells that spontaneously organize into
a ductal structure with basal cells around the periphery and luminal cells lining
an interior cavity, reminiscent of normal mammary duct structure. Lgr5+ cell
derived organoids were sustainable during prolonged passaging. In contrast,
although Lgr5- cells expand into primary colonies, colony-forming efficiency
immediately dissipated upon passaging. Furthermore, reproductive hormones induce
epithelial cell proliferation resulting in marked increases in lumen diameter
accompanied by squamous transdifferentiation. We propose this estrogen
responsive, self-organizing duct-like structure derived from single murine Lgr5+
mammary cells represents a "mini-breast" organoid.
PMID- 27511964
TI - Respiratory and oral vaccination improves protection conferred by the live
vaccine strain against pneumonic tularemia in the rabbit model.
AB - Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium,
Francisella tularensis We have previously shown that rabbits are a good model of
human pneumonic tularemia when exposed to aerosols containing a virulent, type A
strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an
attenuated type B strain, extended time to death when given by scarification.
Oral or aerosol vaccination has been previously shown in humans to offer superior
protection to parenteral vaccination against respiratory tularemia challenge.
Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with
only minimal fever and no weight loss after inoculation. Plasma antibody titers
against F. tularensis were higher in rabbits that were vaccinated by either oral
or aerosol routes compared to scarification. Thirty days after vaccination, all
rabbits were challenged with aerosolized SCHU S4. LVS given by scarification
extended time to death compared to mock-vaccinated controls. One orally
vaccinated rabbit did survive aerosol challenge, however, only aerosol
vaccination extended time to death significantly compared to scarification. These
results further demonstrate the utility of the rabbit model of pneumonic
tularemia in replicating what has been reported in humans and macaques as well as
demonstrating the utility of vaccination by oral and respiratory routes against
an aerosol tularemia challenge.
PMID- 27511966
TI - Relation Between Lack of Forgiveness and Depression: The Moderating Effect of
Self-Compassion.
AB - Although an association between lack of forgiveness and poor mental health is
known, prior studies have reported mixed findings of the relationship between
lack of forgiveness and depressive symptoms. In an attempt to explain the
strength differences between lack of forgiveness and depressive symptoms, this
study examined the moderating effect of self-compassion. A total of 311 Korean
teachers (89 men, 222 women; M age = 39.3 year, SD = 9.1) were asked to complete
self-report questionnaires, including the Korean versions of the Trait
Forgivingness Scale, the Self-Compassion Scale, and the Center for Epidemiologic
Studies Depression Scale. Moderated multiple regression was used for analysis,
and a buffering interaction of self-compassion was discovered. Specifically, self
compassion moderated the relationship between lack of forgiveness and depression;
the relationship was stronger for those low on self-compassion.
PMID- 27511965
TI - The Risk of Atrial Fibrillation With Ivabradine Treatment: A Meta-analysis With
Trial Sequential Analysis of More Than 40000 Patients.
AB - Recent trials reported that risk of atrial fibrillation (AF) is increased in
patients using ivabradine compared with controls. We performed this meta-analysis
to investigate the risk of AF association with ivabradine treatment on the basis
of data obtained from randomized controlled trials (RCTs). We searched PubMed,
EMBASE, Scopus, and the Cochrane Library for RCTs that comprised >100 patients.
The incidence of AF was assessed. We obtained data from European Medicines Agency
(EMA) scientific reports for the RCTs in which the incidence of AF was not
reported. We used trial sequential analysis (TSA) to provide information on when
we had reached firm evidence of new AF based on a 15% relative risk increase
(RRI) in ivabradine treatment. Three RCTs and 1 EMA overall oral safety set
(OOSS) pooled analysis (included 5 RCTs) were included in the meta-analysis (N =
40 437). The incidence of AF was 5.34% in patients using ivabradine and 4.56% in
placebo. There was significantly higher incidence of AF (24% RRI) in the
ivabradine group when compared with placebo before (RR: 1.24, 95% confidence
interval: 1.08-1.42, P = 0.003, I 1980 = 53%) and after excluding OOSS (RR: 1.24,
95% confidence interval: 1.06-1.44, P = 0.008). In the TSA, the cumulative z
curve crossed both the traditional boundary (P = 0.05) and the trial sequential
monitoring boundary, indicating firm evidence for >=15% increase in ivabradine
treatment when compared with placebo. Study results indicate that AF is more
common in the ivabradine group (24% RRI) than in controls.
PMID- 27511967
TI - Relationships Between Refraining From Catastrophic Thinking, Repetitive Negative
Thinking, and Psychological Distress.
AB - Skills to refrain from catastrophic thinking were negatively related to worry and
a wide range of psychological distress. Repetitive negative thinking (including
worry) is proposed as a common etiological factor for a wide range of
psychological distress. Therefore, reduced repetitive negative thinking would
mediate the negative relation between refraining from catastrophic thinking and
psychological distress (depression, social anxiety, phobia, generalized anxiety,
and obsessions and compulsions). As an overlap between five indices of
psychological distress was expected, we first computed latent factors underlying
them, which were then predicted by refraining from catastrophic thinking and
repetitive negative thinking. Cross-sectional questionnaire data from 125
nonclinical voluntarily participating students (M age = 19.0 years, SD = 3.6; 54%
women) supported the predictions: refraining from catastrophic thinking was
negatively correlated with depression, social anxiety, phobia, generalized
anxiety, and obsession and compulsion. Repetitive negative thinking mediated the
negative relationship between refraining from catastrophic thinking and latent
factors underlying psychological distress (Fear and Distress). Refraining from
catastrophic thinking may be negatively correlated with psychological distress
due to its negative relation to repetitive negative thinking.
PMID- 27511968
TI - Psychological insulin resistance: scope of the problem.
PMID- 27511969
TI - Babesiosis acquired from a pet dog: a second reported case in Hong Kong.
PMID- 27511970
TI - Intracoronary thrombus in an 18-year-old teenager. Why?
PMID- 27511971
TI - Neurocysticercosis in a young Indian male.
PMID- 27511972
TI - Crowned dens syndrome: an uncommon cause of cord compression.
PMID- 27511973
TI - Myocardial Contrast Stress Echo Versus Fractional Flow Reserve: A Fair Fight
Among Ischemic Tests?
PMID- 27511974
TI - Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident
Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).
AB - BACKGROUND: Early detection of structural changes in left atrium (LA) before
atrial fibrillation (AF) development could be helpful in identification of those
at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the
association of LA volume and function, and incident AF in a multiethnic
population free of clinical cardiovascular diseases. METHODS AND RESULTS: In a
case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis),
baseline LA size and function assessed by cardiac magnetic resonance feature
tracking were compared between 197 participants with incident AF and 322
participants randomly selected from the whole MESA cohort. Participants were
followed up for 8 years. Incident AF cases had a larger LA volume and decreased
passive, active, and total LA emptying fractions and peak global LA longitudinal
strain (peak LA strain) at baseline. In multivariable analysis, elevated LA
maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01
1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence
interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio
for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40
0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95%
confidence interval, 0.52-0.95), but not active LA emptying fraction, were
associated with incident AF. CONCLUSIONS: Elevated LA volumes and decreased
passive and total LA emptying fractions were independently associated with
incident AF in an asymptomatic multiethnic population. Including LA functional
variables along with other risk factors of AF may help to better risk stratify
individuals at risk of AF development.
PMID- 27511975
TI - Sex Differences in Nonculprit Coronary Plaque Microstructures on Frequency-Domain
Optical Coherence Tomography in Acute Coronary Syndromes and Stable Coronary
Artery Disease.
AB - BACKGROUND: Numerous reports suggest sex-related differences in atherosclerosis.
Frequency-domain optical coherence tomography has enabled visualization of plaque
microstructures associated with disease instability. The prevalence of plaque
microstructures between sexes has not been characterized. We investigated sex
differences in plaque features in patients with coronary artery disease. METHODS
AND RESULTS: Nonculprit plaques on frequency-domain optical coherence tomography
imaging were compared between men and women with either stable coronary artery
disease (n=320) or acute coronary syndromes (n=115). A greater prevalence of
cardiovascular risk factors was observed in women. Nonculprit plaques in women
with stable coronary artery disease were more likely to exhibit plaque erosion
(8.6% versus 0.3%; P=0.03) and a smaller lipid arc (163.1+/-71.4 degrees versus
211.2+/-71.2 degrees ; P=0.03), and less likely to harbor cholesterol crystals
(17.2% versus 27.5%; P=0.01) and calcification (15.4% versus 34.4%; P=0.008),
whereas fibrous cap thickness (105.2+/-62.1 versus 96.1+/-40.4 um; P=0.57), the
prevalence of thin-cap fibroatheroma (26.5% versus 25.2%; P=0.85), and
microchannels (19.2% versus 20.5%; P=0.95) were comparable. In women with acute
coronary syndrome, a smaller lipid arc (171.6+/-53.2 degrees versus 235.8+/-86.4
degrees ; P=0.03), a higher frequency of plaque erosion (11.4% versus 0.6%;
P=0.04), and a lower prevalence of cholesterol crystal (28.6% versus 38.2%;
P=0.03) and calcification (10.0% versus 23.7%; P=0.01) were observed. These
differences persisted after adjusting clinical demographics. Although thin-cap
fibroatheromas in men clustered within proximal arterial segments, thin-cap
fibroatheromas were evenly distributed in women. CONCLUSIONS: Despite more
comorbid risk factors in women, their nonculprit plaques exhibited more plaque
erosion, and less cholesterol and calcium content. This distinct phenotype
suggests sex-related differences in the pathophysiology of atherosclerosis.
PMID- 27511976
TI - Understanding the Risk to Develop Atrial Fibrillation: And What Cardiac Magnetic
Resonance Can Add.
PMID- 27511977
TI - Insights Into Coronary Plaque Microstructure Differences Between Women and Men.
PMID- 27511978
TI - Comparison of Fractional Flow Reserve Assessment With Demand Stress Myocardial
Contrast Echocardiography in Angiographically Intermediate Coronary Stenoses.
AB - BACKGROUND: Real-time myocardial contrast echocardiography (RTMCE) directly
measures capillary flow (CBF), which in turn is a major regulator of coronary
flow and resistance during demand or hyperemic stress. Although fractional flow
reserve (FFR) was developed to assess the physiological relevance of an
epicardial stenosis, it assumes maximal microvascular vasodilation and minimal
resistance during vasodilator stress. Therefore, we sought to determine the
relationship between CBF assessed with RTMCE during stress echocardiography and
FFR in intermediate coronary lesions. METHODS AND RESULTS: Sixty-seven vessels
with 50% to 80% diameter stenoses by quantitative coronary angiography in 58
consecutive patients were examined with FFR and RTMCE (mean age, 60+/-13 years).
RTMCE was performed using an incremental dobutamine (n=32) or exercise (n=26)
stress protocol, and myocardial perfusion was assessed using a continuous
infusion of ultrasound contrast. The presence or absence of inducible perfusion
defects and wall motion abnormalities were correlated with FFR. Mean percent
diameter stenosis was 60+/-9%. Eighteen stenoses (27%) had an FFR <= 0.8.
Although 17 of the 18 stenoses that were FFR+ had abnormal CBF during RTMCE, 28
of the 49 stenoses (57%) that were FFR had abnormal CBF, and 24 (49%) had
abnormal wall motion in the corresponding coronary artery territory during stress
echocardiography. CONCLUSIONS: In a significant percentage of intermediate
stenoses with normal FFR values, CBF during demand stress is reduced, resulting
in myocardial ischemia.
PMID- 27511980
TI - Prognostic Significance of Occult Transthyretin Cardiac Amyloidosis in Patients
With Severe Aortic Stenosis Undergoing Surgical Aortic Valve Replacement: An
Unrecognized Disease Modifier.
PMID- 27511979
TI - Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis:
Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve
Replacement.
AB - BACKGROUND: Calcific aortic stenosis (cAS) affects 3% of individuals aged >75
years, leading to heart failure and death unless the valve is replaced. Wild-type
transthyretin cardiac amyloid is also a disorder of ageing individuals.
Prevalence and clinical significance of dual pathology are unknown. This study
explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial
biopsy, its imaging phenotype and prognostic significance. METHODS AND RESULTS: A
total of 146 patients with severe AS requiring surgical valve replacement
underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had
cAS (75+/-6 years; 57% men). Amyloid was sought histologically using Congo red
staining and then typed using immunohistochemistry and mass spectrometry;
patients with amyloid underwent clinical evaluation including genotyping and
(99m)TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy.
Amyloid was identified in 6 of 146 patients, all with cAS and >65 years
(prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid
(mean age 75 years; range, 69-85; 4 men), not suspected on echocardiography.
Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis
in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans
demonstrated cardiac localization in all 4 patients who had this investigation (2
died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus
7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of
transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5
[95% confidence interval, 2.5-35.8]; P=0.001). CONCLUSIONS: Occult wild-type
transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged
>65 years undergoing surgical aortic valve replacement and was associated with a
poor outcome.
PMID- 27511981
TI - Bone cement with a modified polyphosphate network structure stimulates hard
tissue regeneration.
AB - In this study, a calcium polyphosphate cement (CpPC) consisting of basic
components was investigated to assess its potential for hard tissue regeneration.
The added basic components for improving the structural stability, which
controlled the setting time, where the setting reaction resulted in the formation
of amorphous structure with a re-constructed polyphosphate. Moreover, the
characteristics were controlled by the composition, which determined the
polyphosphate structure. CpPC exhibited outstanding dissolution rate compared
with the common biodegradable cement, brushite cement (2.5 times). Despite high
amounts of dissolution products, no significant cytotoxicity ensued. Induction of
calcification in MG-63 cells treated with CpPC, the level of calcification
increased with increasing CpPC dissolution rate. Induced calcification was
observed also in CpPC-treated ST2 cells, in contrast with MG-63 and ST2 treated
with brushite cement, for which no calcification was observed. In vivo tests
using a rat calvarial defect model showed that resorbed CpPC resulted in
favorable host responses and promoted bone formation. Additionally, there was a
significant increase in defect closure, and new bone formation progressed from
CpPC mid-sites as well as defect margins. From these results, CpPC exhibits
significant potential as biodegradable bone substitute for bone regeneration.
PMID- 27511982
TI - Elution profiles of tobramycin and vancomycin from high-purity calcium sulphate
beads incubated in a range of simulated body fluids.
AB - The aim of this study was to characterise the elution profiles of antibiotics in
combination with pharmaceutical grade calcium sulphate beads in phosphate
buffered saline and other physiological solutions which more closely mimic the in
vivo environment. Synthetic recrystallised calcium sulphate was combined with
vancomycin hydrochloride powder and tobramycin sulphate solution and the paste
was formed into 3 mm diameter hemispherical beads. Then 2 g of beads were
immersed in 2 ml of either phosphate buffered saline, Dulbecco's Modified Eagle
Medium or Hartmann's solution and incubated at 37C for up to 21 days. At a range
of time points, eluent was removed for analysis by liquid chromatography-mass
spectrometry (LC-MS). Tobramycin sulphate and vancomycin hydrochloride release
was successfully quantified against standard curves from solutions eluted in all
three physiological media (phosphate buffered saline, Dulbecco's Modified Eagle
Medium and Hartmann's solution) during incubation with calcium sulphate beads.
One hour eluate concentrations were high, up to 2602 ug/ml for tobramycin in
phosphate buffered saline and 7417 ug/ml for vancomycin, whereas in DMEM, the
levels of tobramycin were 2458 ug/ml and 4401 ug/ml for vancomycin. The levels in
HRT were 2354 ug/ml for tobramycin and 5948 ug/ml for vancomycin. The results
show highest levels of antibiotic elution over the first 24 h, which gradually
diminish over the following 21 days.
PMID- 27511983
TI - Extrapancreatic effects of incretin hormones: evidence for weight-independent
changes in morphological aspects and oxidative status in insulin-sensitive organs
of the obese nondiabetic Zucker rat (ZFR).
AB - Incretin-based therapies are widely used to treat type 2 diabetes. Although
hypoglycemic actions of incretins are mostly due to their
insulinotropic/glucagonostatic effects, they may also influence extrapancreatic
metabolism. We administered exendin-4 (Ex-4), a long-acting glucagon-like peptide
receptor agonist, at low dose (0.1 nmol/kg/day) for a short period (10 days), in
obese nondiabetic fa/fa Zucker rats (ZFRs). Ex-4-treated ZFRs were compared to
vehicle (saline)-treated ZFRs and vehicle- and Ex-4-treated lean rats (LRs).
Blood glucose levels were measured at days 0, 9, and 10. Ingested food and animal
weight were recorded daily. On the day of sacrifice (d10), blood was sampled
along with liver, epididymal, subcutaneous, brown adipose, and skeletal muscle
tissues from animals fasted for 24 h. Plasma insulin and blood glucose levels,
food intake, and body and epididymal fat weight were unchanged, but gross
morphological changes were observed in insulin-sensitive tissues. The average
size of hepatocytes was significantly lower in Ex-4-treated ZFRs, associated with
decreased number and size of lipid droplets and 4-hydroxy-2-nonenal (HNE)
staining, a marker of oxidative stress (OS). Myocytes, which were smaller in ZFRs
than in LRs, were significantly enlarged and depleted of lipid droplets in Ex-4
treated ZFRs. Weak HNE staining was increased by Ex-4. A similar observation was
made in brown adipose tissue, whereas the elevated HNE staining observed in
epididymal adipocytes of ZFRs, suggestive of strong OS, was decreased by Ex-4.
These results suggest that incretins by acting on OS in insulin-sensitive tissues
may contribute to weight-independent improvement in insulin sensitivity.
PMID- 27511984
TI - Mitochondrial function assessed by 31P MRS and BOLD MRI in non-obese type 2
diabetic rats.
AB - The study aims to characterize age-associated changes in skeletal muscle
bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal
muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes
(T2D). (31)P magnetic resonance spectroscopy (MRS) and blood oxygen level
dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult
(20 weeks) GK and Wistar (control) rats. (31)P-MRS and BOLD-MRI data were
acquired continuously during an ischemia and reperfusion protocol to quantify
changes in phosphate metabolites and muscle oxygenation. The time constant of
phosphocreatine recovery, an index of mitochondrial oxidative capacity, was not
statistically different between GK rats (60.8 +/- 13.9 sec in young group, 83.7
+/- 13.0 sec in adult group) and their age-matched controls (62.4 +/- 11.6 sec in
young group, 77.5 +/- 7.1 sec in adult group). During ischemia, baseline
normalized BOLD-MRI signal was significantly lower in GK rats than in their age
matched controls. These results suggest that insulin resistance leads to
alterations in tissue metabolism without impaired mitochondrial oxidative
capacity in GK rats.
PMID- 27511985
TI - The response of muscle protein synthesis following whole-body resistance exercise
is greater following 40 g than 20 g of ingested whey protein.
AB - The currently accepted amount of protein required to achieve maximal stimulation
of myofibrillar protein synthesis (MPS) following resistance exercise is 20-25 g.
However, the influence of lean body mass (LBM) on the response of MPS to protein
ingestion is unclear. Our aim was to assess the influence of LBM, both total and
the amount activated during exercise, on the maximal response of MPS to ingestion
of 20 or 40 g of whey protein following a bout of whole-body resistance exercise.
Resistance-trained males were assigned to a group with lower LBM (<=65 kg; LLBM n
= 15) or higher LBM (>=70 kg; HLBM n = 15) and participated in two trials in
random order. MPS was measured with the infusion of (13)C6-phenylalanine tracer
and collection of muscle biopsies following ingestion of either 20 or 40 g
protein during recovery from a single bout of whole-body resistance exercise. A
similar response of MPS during exercise recovery was observed between LBM groups
following protein ingestion (20 g - LLBM: 0.048 +/- 0.018%.h(-1); HLBM: 0.051 +/-
0.014%.h(-1); 40 g - LLBM: 0.059 +/- 0.021%.h(-1); HLBM: 0.059 +/- 0.012%.h(-1)).
Overall (groups combined), MPS was stimulated to a greater extent following
ingestion of 40 g (0.059 +/- 0.020%.h(-1)) compared with 20 g (0.049 +/-
0.020%.h(-1); P = 0.005) of protein. Our data indicate that ingestion of 40 g
whey protein following whole-body resistance exercise stimulates a greater MPS
response than 20 g in young resistance-trained men. However, with the current
doses, the total amount of LBM does not seem to influence the response.
PMID- 27511986
TI - Clinical predictors for high-grade bladder cancer before first-time transurethral
resection of the bladder tumor: a retrospective cohort study.
AB - The aim of this study was to identify the clinical predictors related to the risk
of high-grade bladder cancer before first-time transurethral resection of the
bladder tumor (TUR-Bt) and to externally validate the accuracy of Shapur's
nomogram predicting the risk of high-grade bladder cancer in Japanese patients.
As a result, episode of gross hematuria (odds ratio: 2.68, P = 0.02), larger
tumor size (odds ratio: 1.89, P < 0.01) and positive urinary cytology (odds
ratio: 8.34, P < 0.01) were found to be significant predictors for high-grade
bladder cancer. Furthermore, the nomogram showed a high predictive accuracy in
our Japanese population (area under the curve: 0.79). Clinicians will be able to
predict high-grade bladder cancer using the common factors in Shapur's study and
ours, such as tumor size and urinary cytology, and gross hematuria as the
additional factor first identified here to decide priorities for the treatment of
patients diagnosed with bladder cancer.
PMID- 27511988
TI - Dosimetric comparison between proton beam therapy and photon radiation therapy
for locally advanced non-small cell lung cancer.
AB - OBJECTIVE: To assess the feasibility of proton beam therapy for the patients with
locally advanced non-small lung cancer. METHODS: The dosimetry was analyzed
retrospectively to calculate the doses to organs at risk, such as the lung,
heart, esophagus and spinal cord. A dosimetric comparison between proton beam
therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy)
plans was performed. Dummy intensity-modulated radiotherapy plans were also
generated for the patients for whom curative three-dimensional conformal
radiotherapy plans could not be generated. RESULTS: Overall, 33 patients with
stage III non-small cell lung cancer were treated with proton beam therapy
between December 2011 and August 2014. The median age of the eligible patients
was 67 years (range: 44-87 years). All the patients were treated with
chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median
prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was
23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0
19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean
heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose
was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal
radiotherapy planning, 12 patients were regarded as not being suitable for
radical thoracic three-dimensional conformal radiotherapy. All the dose
parameters of proton beam therapy, except for the esophageal dose, were lower
than those for the dummy three-dimensional conformal radiotherapy plans. In
comparison to the intensity-modulated radiotherapy plan, proton beam therapy also
achieved dose reduction in the normal lung. None of the patients experienced
grade 4 or worse non-hematological toxicities. CONCLUSIONS: Proton beam therapy
for patients with stage III non-small cell lung cancer was feasible and was
superior to three-dimensional conformal radiotherapy for several dosimetric
parameters.
PMID- 27511987
TI - Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review
and meta-analysis of epidemiologic studies.
AB - OBJECTIVE: Systematic evaluation of the association between secondhand smoke
exposure and lung cancer in Japan has yet to be conducted. Here, we performed a
systematic review and meta-analysis of the relationship between secondhand smoke
and lung cancer in Japanese non-smokers. METHODS: Relevant studies were collected
from the MEDLINE and Ichushi Web databases using a combination of search terms
and Medical Subject Headings. Eligible studies were identified, and relative
risks or odds ratios were extracted to calculate pooled risk estimates. This
procedure was performed independently by at least two authors. Stratified
analyses were carried out according to study design, publication year, and
whether or not potential confounding variables were accounted for. The presence
of publication bias was assessed via funnel plots. RESULTS: We identified four
cohort studies and five case-control studies. Quantitative synthesis was
conducted only for secondhand smoke exposure in the home during adulthood. Of the
12 populations included in meta-analysis, positive secondhand smoke exposure-lung
cancer associations were observed in 11, whereas an inverse association was found
in the remaining 1. The pooled relative risk of lung cancer associated with
secondhand smoke exposure was 1.28 (95% confidence interval: 1.10-1.48). We found
no evidence of publication bias, and a significant association remained even when
potentially missing studies were included (pooled relative risk: 1.26; 95%
confidence interval: 1.09-1.46). The results were stable across different
subgroup analyses, including by study design, publication year, and when
adjusting for confounding variables. CONCLUSIONS: Secondhand smoke exposure in
the home during adulthood results in a statistically significant increase in the
risk of lung cancer.
PMID- 27511989
TI - Patterns of failure after postoperative intensity-modulated radiotherapy for
locally advanced and recurrent head and neck cancer.
AB - OBJECTIVE: To evaluate the feasibility of postoperative intensity-modulated
radiotherapy for head and neck cancer by investigating the patterns of failure
after this therapy. METHODS: A retrospective chart review was performed. RESULTS:
Between March 2006 and December 2013, 122 consecutive patients with head and neck
squamous cell carcinoma were treated by surgery followed by postoperative
intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59
(48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the
hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had
cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The
median follow-up period of the surviving patients was 54 months (range, 25-115).
Concurrent chemotherapy was administered in 76 patients (62%). The median
prescribed radiation dose was 66 Gy. The 3-year overall survival, progression
free survival, distant metastasis free survival and loco-regional control rates
were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed
loco-regional recurrence as the initial recurrence, including in-field recurrence
in 26 patients, marginal recurrence in five patients and out-field recurrence in
seven patients. Of the five patients with marginal recurrence, four have had two
or more surgeries before the intensity-modulated radiotherapy and three had oral
cavity cancer. Severe adverse events were not frequent, occurring at a frequency
of <5%, except for mucositis. No severe toxicities associated with the flap
reconstruction were observed either. CONCLUSION: Postoperative intensity
modulated radiotherapy appears to be effective and feasible for patients with
head and neck squamous cell carcinoma.
PMID- 27511990
TI - Relationship of tumor PD-L1 expression with EGFR wild-type status and poor
prognosis in lung adenocarcinoma.
AB - BACKGROUND: Programmed death-ligand 1 is an immune modulator that promotes
immunosuppression by binding to programmed death-1 of T-lymphocytes. Whereas
programmed death-ligand 1 expression has been shown to be associated with the
clinical response to anti-programmed death-ligand 1 antibody, the association of
tumor programmed death-ligand 1 expression with clinicopathological/molecular
features and with prognosis remains inconclusive in lung adenocarcinoma. We
therefore examined the association of programmed death-ligand 1 expression with
the clinicopathological/molecular features and prognosis of lung adenocarcinoma.
METHODS: Using tissue microarrays of 268 consecutive cases of lung
adenocarcinoma, we evaluated programmed death-ligand 1 expression by
immunohistochemistry. We examined the association of programmed death-ligand 1
expression with clinicopathological and molecular features. We also examined the
prognostic association of programmed death-ligand 1 expression, using the log
rank test as well as Cox proportional hazards regression models to compute the
mortality hazard ratio (HR). RESULTS: Programmed death-ligand 1 immunoreactivity
(at least 5% of the tumor cells) was observed in 43 (16%) of 268 cases of lung
adenocarcinoma. Programmed death-ligand 1 positivity was associated with less
tumor differentiation (P < 0.0001) and EGFR wild-type status (P = 0.0008). In a
multivariable logistic regression analysis, less tumor differentiation was
independently associated with programmed death-ligand 1 positivity (multivariable
odds ratio, 6.54; 95% confidence interval [CI], 2.37-23.3; P = 0.0001).
Programmed death-ligand 1 positivity was associated with a poor prognosis for
lung cancer-specific survival (log-rank, P = 0.019; HR, 1.73; 95% CI, 1.06-2.72;
P = 0.030) and overall survival (log-rank, P = 0.0014; HR, 1.88; 95% CI, 1.25
2.74). CONCLUSION: Our study demonstrated that programmed death-ligand 1
positivity in lung adenocarcinoma was associated with less tumor differentiation
and EGFR wild-type status, as well as a poor prognosis.
PMID- 27511991
TI - A simple home-based self-monitoring tool for early detection of hand-foot
syndrome in cancer patients.
AB - OBJECTIVE: Development of hand-foot syndrome symptoms, which is a common adverse
effect of several cancer chemotherapy agents, can result in patient withdrawal
from treatment. Its early identification allows appropriate modification of
chemotherapy regimens and can avert treatment withdrawal by minimizing the impact
on quality of life and duration of discontinued therapy. We sought to develop a
simple home-based self-monitoring tool to facilitate reliable early
identification of hand-foot syndrome, based on the self-administered quality of
life questionnaire hand-foot syndrome-14. METHODS: We modified the hand-foot
syndrome-14 to create a simple tool with binary responses ('yes' or 'no') for
patients to self-evaluate subjective hand-foot syndrome symptoms daily. We
evaluated this tool with 187 consecutive, consenting, eligible adult patients
attending four centers and treated with capecitabine, sorafenib or sunitinib for
various cancers. Univariate and multivariate logistic regression analyses were
used to select the items with the greatest discrimination for detecting Common
Terminology Criteria for Adverse Events (CTCAE) grade 2 or 3 reactions, which
indicate the need to modify the treatment regimen. RESULTS: There were four items
that were most strongly associated with Common Terminology Criteria for Adverse
Events grade 2 or higher symptoms. 'Pain associated with hand-foot syndrome' was
the most strongly associated with moderate hand-foot syndrome. For detecting
moderate hand-foot syndrome symptoms, the sensitivity was 100.0%, specificity was
94.6%, positive predictive value was 82.6% and area under the curve was 0.98 by a
sum of the scores of four-item self-monitoring tool with cut-off value.
CONCLUSIONS: We present a simple self-monitoring tool that can be used at home
with high sensitivity and specificity for identifying grade 2 hand-foot syndrome.
In addition, this tool might facilitate self-care.
PMID- 27511992
TI - Comparison of visual assessment and image analysis in the evaluation of Ki-67
expression and their prognostic significance in immunohistochemically defined
luminal breast carcinoma.
AB - OBJECTIVES: To compare the Ki-67 labeling index value obtained through
immunohistochemistry analysis by human examiners to that obtained from computer
assisted image analysis, and to establish a cut-off value for Ki-67 labeling
index for each method in luminal B breast carcinoma. METHODS:
Immunohistochemistry analysis for Ki-67 was performed on the formalin-fixed,
paraffin-embedded tissue samples from 403 patients with primary luminal breast
cancers. Whole slide images were obtained using the NanoZoomer (Hamamatsu
Photonics, Hamamatsu, Japan) and thoroughly analyzed using the Definiens Tissue
Studio version 1.1 (Definiens AG, Munich, Germany) to detect the percentage of
positively-stained nuclei of carcinoma cells. RESULTS: Although a significant
correlation was found between the Ki-67 labeling index obtained by manual
assessment and computer-assisted image analysis (Spearman rank correlation
coefficient, P < 0.01), the Ki-67 labeling index value obtained by manual
assessment was significantly higher than that obtained by computer-assisted image
analysis (Wilcoxon signed rank test, P < 0.0001). Disease-free survival was
significantly lower in 403 patients with tumors having high Ki-67 labeling index
values determined by automated analysis (cut-off value: 11.5%; P < 0.00001) and
visual counting (cut-off value: 28.5%; P < 0.00001). Disease-free survival was
also significantly lower in 288 patients who received adjuvant endocrine therapy
alone having high Ki-67 labeling index values determined by automated analysis
(cut-off value: 11.5%; P < 0.0001) and visual counting (cut-off value: 19.7%, P <
0. 0001). CONCLUSIONS: The Ki-67 labeling index values determined by automated
analysis and visual counting could equally predict disease-free survival in
patients with luminal B breast carcinoma, including those who received endocrine
therapy.
PMID- 27511993
TI - Analysis of Gait Disturbance in Glut 1 Deficiency Syndrome.
AB - Anticipating potential therapies for Glut 1 deficiency syndrome (Glut1DS)
emphasizes the need for effective clinical outcome measures. The 6-minute walk
test is a well-established outcome measure that evaluates walking ability in
neurological diseases. Twenty-one children with Glut 1 deficiency syndrome and 21
controls performed the 6-minute walk test. Fatigue was determined by comparing
distance walked in the first and sixth minutes. Gait was analyzed by stride
length, velocity, cadence, base of support, and percentage time in double
support. Independent sample t-tests examined differences between group. Repeated
measures analysis of variance evaluated gait parameters over time. Glut 1
deficiency syndrome patients walked less (P < .05), had slower velocities (P <
.0001), had shorter stride lengths (P < .0001), spent more time in double support
(P < .001), and had increasing variability in base of support (P = .009). Glut 1
deficiency syndrome patients have impaired motor performance, walk more slowly,
and have poor balance. The 6-minute walk test with gait analysis may serve as a
useful outcome measure in clinical trials in Glut 1 deficiency syndrome.
PMID- 27511994
TI - Role of glutathione metabolism and glutathione-related antioxidant defense
systems in hypertension.
AB - The risk of developing chronic hypertension increases with age. Among others
factors, increased oxidative stress is a well-recognized etiological factor for
the development of hypertension. The co-occurrence of oxidative stress and
hypertension may occur as a consequence of a decrease in antioxidant defense
system activity or elevated reactive oxygen species generation. Glutathione is a
major intracellular thiol-disulfide redox buffer that serves as a cofactor for
many antioxidant enzymes. Glutathione-related parameters are altered in
hypertension, suggesting that there is an association between the glutathione
related redox system and hypertension. In this review, we provide mechanistic
explanations for how glutathione maintains blood pressure. More specifically, we
discuss glutathione's role in combating oxidative stress and maintaining nitric
oxide bioavailability via the formation of nitrosothiols and nitrosohemoglobin.
Although impaired vasodilator responses are observed in S-nitrosothiol-deficient
red blood cells, this potential hypertensive mechanism is currently overlooked in
the literature. Here we fill in this gap by discussing the role of glutathione in
nitric oxide metabolism and controlling blood pressure. We conclude that
disturbances in glutathione metabolism might explain age-dependent increases in
blood pressure.
PMID- 27511995
TI - Effect of ethanol and acetaldehyde at clinically relevant concentrations on
atrial inward rectifier potassium current IK1: separate and combined effect.
AB - Atrial fibrillation is the most common arrhythmia at alcohol consumption. Its
pathogenesis is complex, at least partly related to changes of cardiac inward
rectifier potassium currents including IK1. Both ethanol and acetaldehyde have
been demonstrated to considerably modify IK1 in rat ventricular myocytes.
However, analogical data on the atrial IK1 are lacking. The present study aimed
to analyse IK1 changes induced by ethanol and acetyldehyde in atrial myocytes.
The experiments were performed by the whole cell patch-clamp technique at 23 +/-
1 degrees C on enzymatically isolated rat and guinea-pig atrial myocytes as well
as on expressed human Kir2.3 channels. Ethanol (8 - 80 mM) caused a dual effect
on the atrial IK1 showing the steady-state activation in some cells but
inhibition in others in agreement with the ventricular data; on average, the
activation was observed (at 20 mM by 4.3 and 4.5% in rat and guinea-pig atrial
myocytes, respectively). The effect slightly increased with depolarization above
60 mV. In contrast, the current through human Kir2.3 channels (prevailing atrial
IK1 subunit) was inhibited in all measured cells. Unlike ethanol, acetaldehyde (3
MUM) markedly inhibited the rat atrial IK1 (by 15.1%) in a voltage-independent
manner, comparably to the rat ventricular IK1. The concurrent application of
ethanol (20 mM) and acetaldehyde (3 MUM) resulted in the steady-state IK1
activation by 2.1% on average. We conclude that ethanol and even more
acetaldehyde affected IK1 at clinically relevant concentrations if applied
separately. Their combined effect did not significantly differ from the effect of
ethanol alone.
PMID- 27511996
TI - The expression profile of angiogenic genes in critical limb ischemia popliteal
arteries.
AB - Critical limb ischemia (CLI) represents the most severe form of peripheral
arterial disease (PAD) and is the leading cause of non-traumatic amputations in
western populations. In recent years, therapeutic angiogenesis has been
considered to be a potential treatment option for CLI patients, however the
molecular mechanism of ischemia-induced vascularization is still not fully
understood. The identification of genetic factors underlying vascular responses
to ischemia will improve our understanding of the biological causes of the
disease and enhance personalized therapies in the future. In this work, we
determined, for the first time, the expression profile of angiogenesis-related
genes utilizing unique human material: the popliteal arteries retrieved during
lower limb amputation from patients with CLI. Using custom-designed TaqMan Low
Density Array (TLDA) cards we investigated the mRNA level of 90 genes on CLI
samples compared to healthy donors. We identified three significantly up
regulated genes in CLI group: matrix metalloproteinase 9 (MMP-9), VE-cadherin
(CDH5) and integrin alpha 4 (ITGA4). However, among all investigated genes, only
lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) was significantly
reduced. In order to verify whether hypoxic conditions occur in popliteal
arteries of CLI patients, we validated the transcription level of selected
proangiogenic genes by real-time PCR on a larger number of samples. These results
showed that the expression of key genes involved in angiogenesis, such as MMP9,
HGF, HIF1A, VEGF-A and FLT1 were elevated in patients with CLI. Moreover, the
study revealed that the expression of VEGF-A and FLT1 was associated with
activation of HIF1A transcription. In conclusion, our data revealed the
alteration in the mRNA level of genes involved in matrix remodelling, cell-cell
adhesion as well as endothelial cell migration and proliferation in human
popliteal arteries.
PMID- 27511997
TI - Stereoselectivity of tradinterol's inhibition on proliferation of airway smooth
muscle cells induced by acetylcholine through suppressing Ca(2+) signalling.
AB - The objective of this study is to investigate whether the inhibition of
tradinterol (SPFF) against acetylcholine (ACh)-induced proliferation is mediated
by Ca(2+) signaling in airway smooth muscle cells (ASMCs), and whether
stereoselectivity of the drug exists. Guinea pig ASMCs were primarily prepared
with the method described and treated with ACh combined to SPFF isomers for 24 or
48 hours, respectively. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium
bromide (MTT) assay was used to determine the proliferation of the guinea pig
ASMCs. Ca(2+) fluorescent intensity in the guinea pig ASMCs, expressed with
percentage increase in fluorescence when the intensity was determined with
varioskan flash or shown with percentage increase in Geo Mean (GM) measured with
flow cytometry, was recorded. Images of the intensity were obtained with
fluorescent microscope. 2-APB, an (inositol 1,4,5-trisphosphate receptor) IP3R
blocker, and NiCl2, a store-operated channel (SOC) inhibitor, were used to
investigate the mechanism of SPFF isomers regulating intracellular Ca(2+) via
IP3R on sarcoplasmic reticulum (SR) and/or SOC on plasma membrane. (-)SPFF and
(+/-)SPFF, treated for 48 hours, showed significant inhibition against ACh
induced proliferation. The Ca(2+) elevation induced by ACh was concentration
dependently suppressed by SPFF isomers. (-)SPFF is the most effective but the
potency of (+/-)SPFF is less than that of the former and stronger than that of
(+)SPFF based on the half maximal inhibitory concentration (IC50) value. No
significant additive effect was observed when (-)SPFF/(+/-)SPFF was used alone
and combined with NiCl2/2-APB. As far as (+)SPFF is concerned, no similar
phenomenon was observed. (-)SPFF and (+/-)SPFF but (+)SPFF showed significant
inhibition against the percentage increase in fluorescence induced by CaCl2. It
is likely that the influence of IP2RSOC-mediated Ca(2+) signaling in ASMCs helps
(-)SPFF and (+/-)SPFF contribute to the suppression of ASMCs proliferation.
Stereoselectivity of SPFF isomers may lead to different levels of suppression of
ACh-induced intracellular Ca(2+) and ASMCs proliferation. Moreover, cell cycle
analysis with flow cytometry was applied to the evaluation of the action in human
ASMCs in order to further confirm the anti-proliferative effect of the drugs. It
was found that (-)SPFF, (+/-)SPFF but (+)SPFF suppressed the elevated rate of
cell population in Phase S over all the cells stimulated with ACh, when SPFF and
its isomers were individually exposed to the cells for 72 hours. These results
that demonstrate the different stereoselective activities of SPFF are in
consistent with those obtained from the guinea pig ASMCs.
PMID- 27511998
TI - 11-dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in
patients with peripheral arterial occlusive disease during a one year follow-up
period.
AB - The aim of our study was to determine if the generation of thromboxane is altered
in patients with peripheral arterial occlusive disease following percutaneous
transluminal angioplasty (PTA) during a one year follow-up period. In this study,
175 patients diagnosed with peripheral arterial occlusive disease (PAOD) and
demonstrating short-distance claudication or ischemic rest pain, requiring PTA in
either the iliac, femoral, or popliteal arteries, were enrolled. The excretion of
11-dehydro thromboxane B2 (TXB2) was measured in urine samples by high
performance liquid chromatography-mass spectrometry and recalculated based on the
creatinine concentration. The urine samples were collected the morning prior to
PTA, immediately following PTA and the day after PTA. All of the study subjects
were then observed for a period of 12 months. Urine samples were also collected
during the follow-up visits, and the levels of 11-dehydro TXB2 were measured at 1
month (1458.1 pg/mg creatinine +/- 1240.8), 3 months (1623.3 pg/mg creatinine +/-
1362.2), 6 months (1314.8 pg/mg creatinine +/- 1378.7) and 12 months (1473.2
pg/mg creatinine +/- 1455.2) after the PTA procedure. All of the patients were
taking 75 mg of aspirin per day throughout the course of the study, as well as 75
mg of clopidogrel for six weeks following PTA. Overall, the mean TXB2 values
immediately after PTA were significantly higher than either before the procedure
(1524.4 pg/mg creatinine +/- 1411.1 vs. 2098.1 pg/mg creatinine +/- 1661.8; P =
0.00002), the day after PTA, or at any other point during the study. Moreover,
preoperative TXB2 levels correlated well with the composite endpoints of death,
myocardial infarction and stroke during the follow-up period (OR 7.42 [CI 95% =
1.2-48.8]; P = 0.02). Our findings suggest that clinicians should consider the
use of TXA2 synthase inhibitors and receptor antagonists in combination with
peripheral percutaneous transluminal angioplasty in patients with peripheral
arterial occlusive disease.
PMID- 27511999
TI - Factors influencing quality of anticoagulation control and warfarin dosage in
patients after aortic valve replacement within the 3 months of follow up.
AB - Warfarin dosage estimation using the pharmacogenetic algorithms has been shown to
improve the quality of anticoagulation control in patients with atrial
fibrillation. We sought to assess the genetic, demographic and clinical factors
that determine the quality of anticoagulation in patients following aortic valve
replacement (AVR). We studied 200 consecutive patients (130 men) aged 63 +/- 12.3
years, undergoing AVR, in whom warfarin dose was established using a
pharmacogenetic algorithm. The quality of anticoagulation within the first 3
months since surgery was expressed as the time of international normalized ratio
(INR) in the therapeutic range (TTR). The median TTR in the entire cohort was
59.6% (interquartile range, 38.7 - 82.7). Ninety-nine (49.5%) patients with TTR
>= 60% did not differ from those with poor anticoagulation control (TTR < 60%)
with regard to demographic and cardiovascular risk factors. Coronary artery
disease (n = 84, 42%) and previous stroke (n = 5, 2.5%) predicted higher TTR,
while possession of CYP2C9*2 variant allele (n = 49, 25%) was associated with
lower TTR (P = 0.01). In turn, VKORC1 c.-1639A, CYP2C9*2 and *3 variants were
independently associated with actual warfarin dose (P < 0.0001). In AVR patients
better anticoagulation control is observed in patients with coronary artery
disease and history of stroke, which might result in part from previous lifestyle
modification and therapy. Possession of CYP2C9*2 and/or CYP2C9*3 allele variants
is associated with lower TTR values and warfarin dose variations in AVR patients,
the latter affected also by VKORC1 c.-1693G>A polymorphism.
PMID- 27512000
TI - Association of the immunohistochemical detection of gamma-glutamyl transferase
expression with clinicopathological findings in postmenopausal women with
endometrioid adenocarcinoma of the uterus.
AB - Gamma-glutamyl transferase (GGT) is a membrane enzyme present not only in the
liver but also in healthy endometrial epithelium. Its overexpression has been
demonstrated in numerous malignancies, where it exerts an anti-apoptotic effect
and causes drug resistance in response to oxidation stress. Aim of the study was
investigation of GGT expression in postmenopausal patients with endometrioid
adenocarcinoma of the uterus (EAC). The material comprised 98 paraffin-embedded
post-operative tumour samples of EAC from postmenopausal patients and a control
group of 60 normal human postmenopausal endometrium samples. For
immunohistochemical specimen staining, polyclonal IgG anti-GGT was used; for GGT
expression measurement, a semi-quantitative method was applied. In EAC patients,
16 (16.33%) were diagnosed as stage IA, 46 (46.93%) as stage IB, 14 (14.29%) as
stage II, and 22 (22.45%) as stage IIIA-C, according to the International
Federation of Gynaecology and Obstetrics (FIGO) classification. Fifty-six
(57.14%) patients were diagnosed with low- or moderate-grade (G1-2) disease, and
42 (42.86%) were diagnosed with high-grade (G3) disease. Cytoplasmic GGT staining
was confirmed in all samples, while apical membrane GGT staining was observed
only in G1-2 EAC specimens and the control group. In G3 EAC specimens, GGT
cytoplasmic staining and high nuclear polymorphism areas were predominantly
shown. Comparable high GGT median apical expression was confirmed in healthy
endometrium (2.0, S.E.M. = 0.28) and in G1-2 EAC (2.0, S.E.M. = 0.27); however,
in G3 tumours, GGT expression was significantly lower (0.0, S.E.M. = 0.07) than
in healthy endometrium (P < 0.001 and P < 0.001, respectively). After
stratification of the cancer cases according to FIGO staging, the lowest median
apical GGT expression levels were in II EAC (0.0, S.E.M. = 0.64) tumours compared
with IA (4.0, S.E.M. = 0.47) tumours, specimen and normal endometrium (2.0,
S.E.M. = 2.8) (P < 0001). Stage IB EAC and IIIA-C EAC (1.0, S.E.M. = 0.16) cases
showed only moderate median apical expression of GGT (1.0, S.E.M. = 0.24). We
concluded that impaired GGT expression has the potential to become a valuable
tool for stratifying EEC patients' prognosis and treatment planning.
PMID- 27512001
TI - The role of apelin in the modulation of gastric and pancreatic enzymes activity
in adult rats.
AB - Apelin is considered as important gut regulatory peptide ligand of APJ receptor
with a potential physiological role in gastrointestinal cytoprotection,
regulation of food intake and drinking behavior. Circulating apelin inhibits
secretion of pancreatic juice through vagal- cholecystokinin-dependent mechanism
and reduces local blood flow. Our study was aimed to determine the effect of
fundectomy and intraperitoneal or intragastric administration of apelin-13 on
pancreatic and gastric enzymes activities in adult rats. Fundectomy is a surgical
removal of stomach fundus - maine site apelin synthesis. Three independent
experiments were carried out on Wistar rats. In the first and second experiment
apelin-13 was given by intragastric or intraperitoneal way twice a day for 10
days (100 nmol/kg b.w.). Control groups received the physiological saline
respectively. In the third experiment the group of rats after fundectomy were
used. Fundectomized rats did not receive apelin and the rats from control group
were 'sham operated'. At the end of experiment rats were sacrificed and blood
from rats was withdrawn for apelin and CCK (cholecystokinin) radioimmunoassay
analysis and pancreas and stomach tissues were collected for enzyme activity
analyses. Intragastric and intraperitoneal administrations of apelin-13 increased
basal plasma CCK level and stimulated gastric and pancreatic enzymes activity in
rats. In animals after fundectomy decreased activity of studied enzymes was
observed, as well as basal plasma apelin and CCK levels. In conclusion, apelin
can effects on CCK release and stimulates some gastric and pancreatic enzymes
activity in adult rats while fudectomy suppresses those processes. Changes in the
level of pancreatic lipase activity point out that apelin may occurs as a
regulator of lipase secretion.
PMID- 27512002
TI - Melatonin metabolite, N(1)-acetyl-N(1)-formyl-5-methoxykynuramine (AFMK),
attenuates acute pancreatitis in the rat: in vivo and in vitro studies.
AB - Melatonin protects the pancreas from inflammation and free radical damage but the
effect of the melatonin metabolite: N(1)-acetyl-N(2)-formyl-5-methoxykynuramine
(AFMK) on acute pancreatitis is unknown. This study assessed the effects of AFMK
on acute pancreatitis (AP) in the rats in vivo and on pancreatic cell line AR42J
in vitro. AFMK (5, 10 or 20 mg/kg) was given intraperitoneally to the rats 30 min
prior to the induction of AP by subcutaneous caerulein infusion (25 MUg/kg).
Lipid peroxidation products (MDA + 4-HNE) and the activity of an antioxidant
enzyme glutathione peroxidase (GPx) were measured in pancreatic tissue. Blood
samples were taken for evaluation of amylase activity and TNF-alpha
concentration. GPx, TNF-alpha, proapoptotic Bax protein, antiapoptotic Bcl-2
protein and the executor of apoptosis, caspase-3, were determined by Western blot
in AR42J cells subjected to AFMK or to melatonin (both used at 10(-12), 10(-10),
or 10(-8)M), without or with addition of caerulein (10(-8)M). AP was confirmed by
histological examination and by serum increases of amylase and TNF-alpha (by 800%
and 300%, respectively). In AP rats, pancreatic MDA + 4-HNE levels were increased
by 300%, whereas GPx was reduced by 50%. AFMK significantly diminished
histological manifestations of AP, decreased serum amylase activity and TNF-alpha
concentrations, reduced MDA + 4-HNE levels and augmented GPx in the pancreas of
AP rats. In AR42J cells, AFMK combined with caerulein markedly increased protein
signals for GPx, Bax, caspase-3 and reduced these for TNF-alpha and Bcl-2. In
conclusion, AFMK significantly attenuated acute pancreatitis in the rat. This may
relate to the antioxidative and anti-inflammatory effects of this molecule and
possibly to the stimulation of proapoptotic signal transduction pathway.
PMID- 27512003
TI - Pituitary galaninergic system activity in female rats: the regulatory role of
gonadal steroids.
AB - The well-recognized sensitivity of the galanin gene in the anterior pituitary
gland to estrogen suggests that estrogen receptor activity may influence the
galaninergic system through modulation of galanin receptor (GALR) gene
expression. Here, we evaluated the following: (i) the effects of estrogen on GALR
mRNA expression; (ii) the estrogen receptor subtype that is specifically involved
in this activity; and (iii) the effects of progesterone in the absence or
presence of estrogen on galanin concentration in anterior pituitary gland. In the
first experiment, ovariectomized 4-month-old rats were pre-treated subcutaneously
with 17beta-estradiol (3 x 20 MUg), the ESR1 (ERalpha) agonist propyl pyrazole
triol (PPT) (3 x 5 mg), and the ESR2 (ERbeta) agonist diarylpropionitrile (DPN)
(3 x 0.5 mg). In the second experiment, 4-month-old ovariectomized females
received daily subcutaneous injections of 17beta-estradiol (3 x 20 MUg),
progesterone (2 x 5 mg), or combined estradiol (3 x 20 MUg) and progesterone (2 x
5 mg). Anterior pituitaries were excised the day after the final 17beta-estradiol
injection (experiment I) and 1 hour after receiving the second progesterone dose.
Relative GALR1, GALR2, and GALR3 mRNA expression was evaluated using quantitative
real-time PCR, and pituitary galanin concentration was determined using a
specific radioimmunoassay. The results revealed that estrogen predominantly
induced a 5-fold increase in GALR3 gene transcription. To a lesser extent, 17beta
estradiol also increased GALR1 mRNA expression, but had no effect on GALR2 mRNA
levels. The estrogen-induced increase in GALR3 gene expression occurred
exclusively through ESR1 activation. The increase in GALR1 gene expression
occurred through activation of both estrogen receptor subtypes, but the ESR2
subtype was predominantly involved. Furthermore, the results revealed that
progesterone regulates the activity of the pituitary galaninergic system by
facilitating estradiol-induced galanin synthesis in the female rat anterior
pituitary gland.
PMID- 27512004
TI - Changes in gonadotropin-releasing hormone and gonadotropin-releasing hormone
receptor gene expression after an increase in carbon monoxide concentration in
the cavernous sinus of male wild boar and pig crossbread.
AB - Previous studies indicate that there are at least a few regulatory systems
involved in photoperiodic synchronisation of reproductive activity, which starts
with the retina and ends at the gonadotropin-releasing hormone (GnRH) pulse
generator. Recently we have shown indicated that the amount of carbon monoxide
(CO) released from the eye into the ophthalmic venous blood depends on the
intensity of sunlight. The aim of this study was to test whether changes in the
concentration of carbon monoxide in the ophthalmic venous blood may modulate
reproductive activity, as measured by changes in GnRH and GnRH receptor gene
expression. The animal model used was mature male swine crossbred from wild boars
and domestic sows (n = 48). We conducted in vivo experiments to determine the
effect of increased CO concentrations in the cavernous sinus of the mammalian
perihypophyseal vascular complex on gene expression of GnRH and GnRH receptors as
well as serum luteinizing hormone (LH) levels. The experiments were performed
during long photoperiod days near the summer solstice (second half of June) and
short photoperiod days near the winter solstice (second half of December). These
crossbred swine demonstrated a seasonally-dependent marked variation in GnRH and
GnRH receptor gene expression and systemic LH levels in response to changes in CO
concentration in ophthalmic venous blood. These results seem to confirm the
hypothesis of humoral phototransduction as a mechanism for some of bright light's
effects in animal chronobiology and the effect of CO on GnRH and GnRH receptor
gene expression.
PMID- 27512005
TI - Effect of adiponectin on the steroidogenic acute regulatory protein, P450 side
chain cleavage enzyme and 3beta-hydroxysteroid dehydrogenase gene expression,
progesterone and androstenedione production by the porcine uterus during early
pregnancy.
AB - Adiponectin and its receptors are expressed in the human and porcine uterus and
this endocrine system has important role in the regulation of reproductive
processes. The expression of steroidogenic acute regulatory protein (StAR) and
3beta-hydroxysteroid dehydrogenase (HSD3B1) were observed in the human and
porcine uterus during the oestrous cycle and pregnancy. The de novo synthesis of
steroids in the uterus might be a crucial factor for effective implantation and
maintenance of pregnancy. We hypothesized that adiponectin modulates the
expression of key enzymes in the synthesis of the steroids: StAR, P450 side chain
cleavage enzyme (CYP11A1) and HSD3B1, as well as progesterone (P4) and
androstenedione (A4) secretion by the porcine uterus. Endometrial and myometrial
explants harvested from gilts (n = 5) on days 10 to 11, 12 to 13, 15 to 16 and 27
to 28 of pregnancy and on days 10 to 11 of the oestrous cycle were cultured in
vitro in the presence of adiponectin (1, 10 MUg/ml), adiponectin with insulin (10
ng/ml) and insulin alone (10 ng/ml). Gene expression was examined by real-time
PCR, and the secretion of the steroids was determined by radioimmunoassay. The
content of StAR, CYP11A1 and HSD3B1 mRNAs and the secretion of P4 and A4 was
modulated by adiponectin in endometrial and myometrial tissue explants during
early pregnancy and the oestrous cycle. In this action adiponectin interacted
with insulin. Insulin itself also regulated the steroidogenic activity of the
porcine uterus. ere we reported, for the first time, the expression of CYP11A1
genes in the porcine endometrium and myometrium. Our novel findings indicate that
adiponectin affects basal and insulin-stimulated expression of key steroidogenic
genes and production of steroid hormones by the porcine uterus during maternal
recognition of pregnancy and implantation.
PMID- 27512006
TI - The inhibitory effect of combination treatment with leptin and cannabinoid CB1
receptor agonist on food intake and body weight gain is mediated by serotonin 1B
and 2C receptors.
AB - Previous studies reported that the co-injection of leptin and cannabinoid CB1
receptor antagonists reduces food intake and body weight in rats, and this effect
is more profound than that induced by these compounds individually. Additionally,
serotonin mediates the effects of numerous anorectic drugs. To investigate
whether serotonin interacts with leptin and endocannabinoids to affect food
intake and body weight, we administered 5-hydroxytryptamine(HT)1B and 5
hydroxytryptamine(HT)2C serotonin receptor antagonists (3 mg/kg GR 127935 and 0.5
mg/kg SB 242084, respectively) to male Wistar rats treated simultaneously with
leptin (100 MUg/kg) and the CB1 receptor inverse agonist AM 251 (1 mg/kg) for 3
days. In accordance with previous findings, the co-injection of leptin and AM
251, but not the individual injection of each drug, resulted in a significant
decrease in food intake and body weight gain. Blockade of the 5-HT1B and 5-HT2C
receptors completely abolished the leptin- and AM 251-induced anorectic and body
weight-reducing effects. These results suggest that serotonin mediates the leptin
and AM 251-dependent regulation of feeding behavior in rats via the 5-HT1B and 5
HT2C receptors.
PMID- 27512007
TI - The effect of pregabalin - codeine combination on partial sciatic nerve ligation
induced peripheral mononeuropathy in rats.
AB - The present study investigates the effects of pregabalin (PGB) and codeine (COD)
combination on neuropathic hyperalgesia in an animal model of peripheral nerve
injury represented by partial sciatic nerve ligation. Hot plate and analgesimeter
tests were performed to evaluate the influence of PGB, COD and their combination
on thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve
ligation. Reactivity was evaluated by measuring the latency to withdrawal of the
operated hind paw from the noxious heat and pressure stimulation. Nociceptive
thresholds were evaluated before (baseline) and in the 1(st), 3(rd), 5(th) and
7(th) day after surgical procedure. The investigation demonstrates that the
treatment with PGB attenuated partial sciatic nerve ligation development of
thermal and mechanical hyperalgesia in rats operated hind paw. The oral
administration, during 14 consecutive days of PGB-COD combination significantly
reduced the degree of both thermal and mechanical hyperalgesia in the hind paw
with partial sciatic nerve ligation. These results suggest that the association
of PGB with COD exerted ameliorative effect on partial sciatic nerve ligation
induced neuropathic pain in rats.
PMID- 27512008
TI - The antidepressant- and anxiolytic-like effects following co-treatment with
escitalopram and risperidone in rats.
AB - Several clinical reports have documented a beneficial effect of the addition of a
low dose of risperidone to the ongoing treatment with antidepressants, in
particular selective serotonin reuptake inhibitors (SSRI), in the treatment of
drug-resistant depression and treatment-resistant anxiety disorders. In the
present study, we investigated the effect of treatment with the antidepressant
escitalopram (SSRI) given separately or jointly with a low dose of risperidone
(an atypical antipsychotic) in the forced swim test and in the elevated plus-maze
test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5
mg/kg evoked antidepressant-like effect in the forced swim test. Moreover,
risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like
activity of escitalopram (1 mg/kg) in this test by increasing the swimming time
and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5
HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant
like effect induced by co-administration of escitalopram and risperidone. The
active behavior in that test did not reflect an increase in general activity,
since the combined treatment with escitalopram and risperidone failed to enhance
the exploratory activity of rats. In the following experiment, we showed that
escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg)
induced an anxiolytic-like effect in the elevated plus-maze test, and the
combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced
the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5
mg/kg) in this test. The obtained results suggest that risperidone applied at a
low dose enhances the antidepressant-like activity of escitalopram in the forced
swim test, and that 5-HT1A receptors may play some role in these effects.
Moreover, a low dose of risperidone may also enhance the anxiolytic-like action
of the studied antidepressants.
PMID- 27512009
TI - The Inositol Trisphosphate/Calcium Signaling Pathway in Health and Disease.
AB - Many cellular functions are regulated by calcium (Ca(2+)) signals that are
generated by different signaling pathways. One of these is the inositol 1,4,5
trisphosphate/calcium (InsP3/Ca(2+)) signaling pathway that operates through
either primary or modulatory mechanisms. In its primary role, it generates the
Ca(2+) that acts directly to control processes such as metabolism, secretion,
fertilization, proliferation, and smooth muscle contraction. Its modulatory role
occurs in excitable cells where it modulates the primary Ca(2+) signal generated
by the entry of Ca(2+) through voltage-operated channels that releases Ca(2+)
from ryanodine receptors (RYRs) on the internal stores. In carrying out this
modulatory role, the InsP3/Ca(2+) signaling pathway induces subtle changes in the
generation and function of the voltage-dependent primary Ca(2+) signal. Changes
in the nature of both the primary and modulatory roles of InsP3/Ca(2+) signaling
are a contributory factor responsible for the onset of a large number human
diseases.
PMID- 27512010
TI - CXCL3 positively regulates adipogenic differentiation.
AB - Chemokines are a family of cytokines inducing cell migration and inflammation.
Recent reports have implicated the roles of chemokines in cell differentiation.
However, little is known about the functional roles of chemokines in adipocytes.
Here, we explored gene expression levels of chemokines and chemokine receptors
during adipogenic differentiation. We have found that two chemokines, chemokine
(C-X-C motif) ligand 3 (CXCL3) and CXCL13, as well as CXC chemokine receptor 2
(CXCR2), a CXCL3 receptor, are highly expressed in mature adipocytes. When 3T3-L1
cells and ST2 cells were induced to differentiate, both the number of lipid
droplets and the expression levels of adipogenic markers were significantly
promoted by the addition of CXCL3, but not CXCL13. Conversely, gene knockdown of
either CXCL3 or CXCR2 by specific siRNA effectively inhibited the course of
adipogenic differentiation. CXCL3 treatment of 3T3-L1 cells significantly induced
the phosphorylation of ERK and c-jun N-terminal kinase (JNK). Furthermore, CXCL3
induced CCAAT-enhancer binding protein (C/EBP)beta and delta expression was
suppressed by both ERK and JNK-specific inhibitors. Furthermore, chromatin
immunoprecipitation assay revealed functional binding of PPARgamma2 within the
cxcl3 promoter region. Taken together, these results have indicated that CXCL3 is
a novel adipokine that facilitates adipogenesis in an autocrine and/or a
paracrine manner through induction of c/ebpb and c/ebpd.
PMID- 27512011
TI - Elite Distance Runners and Breastfeeding.
AB - BACKGROUND: Elite female distance runners lack guidelines regarding breastfeeding
while training at a high intensity. OBJECTIVES: The purpose of this research was
to understand how elite female distance runners manage breastfeeding. METHODS:
Semistructured interviews were conducted with 14 women who had had at least one
pregnancy within the past 5 years and had achieved a minimum of the USA Track and
Field 2012 Olympic Trials "B" entry standard for running for the marathon or
equivalent performance for 1,500 m or longer. RESULTS: Using thematic analysis,
we identified the following themes: breastfeeding as a barrier to training and
competition, limited access to relevant breastfeeding information, and concerns
for the baby's health. Our findings show that despite the considerable barriers
with which these women contend, they breastfed at higher rates and for longer
duration than members of the general public. CONCLUSION: Based on our findings,
we argue that elite female distance runners' experiences of breastfeeding would
be enhanced if more research were conducted on breastfeeding practices while
training and competing at an elite level.
PMID- 27512012
TI - Are We There Yet? Reliably Estimating the Completeness of Plant Genome Sequences.
AB - Genome sequencing is becoming cheaper and faster thanks to the introduction of
next-generation sequencing techniques. Dozens of new plant genome sequences have
been released in recent years, ranging from small to gigantic repeat-rich or
polyploid genomes. Most genome projects have a dual purpose: delivering a
contiguous, complete genome assembly and creating a full catalog of correctly
predicted genes. Frequently, the completeness of a species' gene catalog is
measured using a set of marker genes that are expected to be present. This
expectation can be defined along an evolutionary gradient, ranging from highly
conserved genes to species-specific genes. Large-scale population resequencing
studies have revealed that gene space is fairly variable even between closely
related individuals, which limits the definition of the expected gene space, and,
consequently, the accuracy of estimates used to assess genome and gene space
completeness. We argue that, based on the desired applications of a genome
sequencing project, different completeness scores for the genome assembly and/or
gene space should be determined. Using examples from several dicot and monocot
genomes, we outline some pitfalls and recommendations regarding methods to
estimate completeness during different steps of genome assembly and annotation.
PMID- 27512013
TI - Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism
without neurological or dental anomalies.
AB - BACKGROUND: A constellation of neurodegenerative disorders exists (Gordon Holmes
syndrome, 4H leucodystrophy, Boucher-Neuhauser syndrome) in which patients suffer
from both neurological disease (typically manifested by ataxia) and reproductive
failure (idiopathic hypogonadotropic hypogonadism (IHH)). POLR3B, which encodes
the second largest subunit of RNA polymerase III (pol III), and POLR3A, which
forms the pol III catalytic centre, are associated with 4H leucodystrophy.
METHODS: Whole exome sequencing was performed on a large cohort of subjects with
IHH (n=565). Detailed neuroendocrine studies were performed in some individuals
within this cohort. RESULTS: Four individuals (two of them siblings) were
identified with two rare nucleotide variants in POLR3B. On initial evaluation,
all subjects were free of neurological disease. One patient underwent treatment
with exogenous pulsatile gonadotropin-releasing hormone for 8 weeks which failed
to result in normalisation of his sex steroid milieu due to pituitary resistance.
CONCLUSIONS: These findings suggest that the spectrum of phenotypes resulting
from POLR3B mutations is wider than previously believed and that POLR3B can be
associated exclusively with disorders characterised by abnormal gonadotropin
secretion.
PMID- 27512014
TI - Quantitative measurement of hydrophilicity/hydrophobicity of the plasma
polymerized naphthalene film (Super Support Film) and other support films and
grids in electron microscopy.
AB - Hydrophilicity/hydrophobicity of the surfaces of plasma-polymerized naphthalene
film (Super Support Film, Nisshin EM Co. Ltd., Tokyo), carbon and formvar support
films, and copper and nickel grids were quantitatively estimated by contact
angles measured from diameters and heights of water droplets placed on various
specimens. With treatment of glow discharge, the surfaces of plasma-polymerized
naphthalene and carbon support films became fully hydrophilic in 20 s. They
remained hydrophilic for 6 h. The surfaces of copper and nickel grids became
fully hydrophilic with 60 s of glow discharge treatment. They remained
hydrophilic for only 1 h. This information is useful for negative staining,
ultrathin sectioning and rapid freezing of biological specimens using the
sandwich method.
PMID- 27512015
TI - Constituent elements and their distribution in the radioactive Cs-bearing
silicate glass microparticles released from Fukushima nuclear plant.
AB - Microparticles of radioactive cesium (Cs)-bearing silicate glass emitted from the
Fukushima Daiichi nuclear power plant were investigated mainly using state-of-the
art energy-dispersive X-ray spectroscopy in scanning transmission electron
microscopes. Precise elemental maps of the particles were obtained using double
silicon drift detectors with a large collection angle of X-rays, and qualitative
elemental analysis was performed using high-resolution X-ray spectroscopy with a
microcalorimetry detector. Beside the substantial elements (O, Si, Cl, K, Fe, Zn,
Rb, Sn and Cs) as previously reported, Mn and Ba were also common, though their
amounts were small. The atomic ratios of the substantial elements were not the
same but varied among individual particles. Fe and Zn were relatively
homogeneously distributed, whereas the concentration of alkali ions varied
radially. Generally, Cs was rich and K and Rb were poor outward of the particles
but the degree of such radial dependence was considerably different among the
particles. A concentration of Sn on the particle surface was observed. High
resolution imaging indicated the formation of SnO2 (cassiterite) nanocrystals on
the surface. Synthesis of the bulk glass with a similar composition to the
microparticles was attempted by quenching the silicate melt from ~1600 degrees C.
However, homogeneous silicate glass like that of the microparticles could not be
obtained due to the segregation of nano-spherules rich in Fe and Zn, suggesting
that the microparticles were formed in a very specific condition in the nuclear
reactor.
PMID- 27512016
TI - Proline Coordination with Fatty Acid Synthesis and Redox Metabolism of
Chloroplast and Mitochondria.
AB - Proline (Pro) accumulation is one of the most prominent changes in plant
metabolism during drought and low water potential; however, the regulation and
function of Pro metabolism remain unclear. We used a combination of forward
genetic screening based on a Proline Dehydrogenase1 (PDH1) promoter-luciferase
reporter (PDH1pro:LUC2) and RNA sequencing of the Pro synthesis mutant p5cs1-4 to
identify multiple loci affecting Pro accumulation in Arabidopsis (Arabidopsis
thaliana). Two mutants having high PDH1pro:LUC2 expression and increased Pro
accumulation at low water potential were found to be alleles of Cytochrome P450,
Family 86, Subfamily A, Polypeptide2 (CYP86A2) and Long Chain Acyl Synthetase2
(LACS2), which catalyze two successive steps in very-long-chain fatty acid
(VLCFA) synthesis. Reverse genetic experiments found additional VLCFA and lipid
metabolism-related mutants with increased Pro accumulation. Altered cellular
redox status is a key factor in the coordination of Pro and VLCFA metabolism. The
NADPH oxidase inhibitor diphenyleneiodonium (DPI) induced high levels of Pro
accumulation and strongly repressed PDH1pro:LUC2 expression. cyp86a2 and lacs2
mutants were hypersensitive to diphenyleneiodonium but could be reverted to wild
type Pro and PDH1pro:LUC2 expression by reactive oxygen species scavengers. The
coordination of Pro and redox metabolism also was indicated by the altered
expression of chloroplast and mitochondria electron transport genes in p5cs1-4
These results show that Pro metabolism is both influenced by and influences
cellular redox status via previously unknown coordination with several metabolic
pathways. In particular, Pro and VLCFA synthesis share dual roles to help buffer
cellular redox status while producing products useful for stress resistance,
namely the compatible solute Pro and cuticle lipids.
PMID- 27512017
TI - The Exonuclease Homolog OsRAD1 Promotes Accurate Meiotic Double-Strand Break
Repair by Suppressing Nonhomologous End Joining.
AB - During meiosis, programmed double-strand breaks (DSBs) are generated to initiate
homologous recombination, which is crucial for faithful chromosome segregation.
In yeast, Radiation sensitive1 (RAD1) acts together with Radiation sensitive9
(RAD9) and Hydroxyurea sensitive1 (HUS1) to facilitate meiotic recombination via
cell-cycle checkpoint control. However, little is known about the meiotic
functions of these proteins in higher eukaryotes. Here, we characterized a RAD1
homolog in rice (Oryza sativa) and obtained evidence that O. sativa RAD1 (OsRAD1)
is important for meiotic DSB repair. Loss of OsRAD1 led to abnormal chromosome
association and fragmentation upon completion of homologous pairing and synapsis.
These aberrant chromosome associations were independent of OsDMC1. We found that
classical nonhomologous end-joining mediated by Ku70 accounted for most of the
ectopic associations in Osrad1 In addition, OsRAD1 interacts directly with OsHUS1
and OsRAD9, suggesting that these proteins act as a complex to promote DSB repair
during rice meiosis. Together, these findings suggest that the 9-1-1 complex
facilitates accurate meiotic recombination by suppressing nonhomologous end
joining during meiosis in rice.
PMID- 27512018
TI - Responses of cerebellar Purkinje cells during fictive optomotor behavior in
larval zebrafish.
AB - Although most studies of the cerebellum have been conducted in mammals,
cerebellar circuitry is highly conserved across vertebrates, suggesting that
studies of simpler systems may be useful for understanding cerebellar function.
The larval zebrafish is particularly promising in this regard because of its
accessibility to optical monitoring and manipulations of neural activity.
Although several studies suggest that the cerebellum plays a role in behavior at
larval stages, little is known about the signals conveyed by particular classes
of cerebellar neurons. Here we use electrophysiological recordings to
characterize subthreshold, simple spike, and climbing fiber responses in larval
zebrafish Purkinje cells in the context of the fictive optomotor response (OMR)-a
paradigm in which fish adjust motor output to stabilize their virtual position
relative to a visual stimulus. Although visual responses were prominent in
Purkinje cells, they lacked the direction or velocity sensitivity that would be
expected for controlling the OMR. On the other hand, Purkinje cells exhibited
strong responses during fictive swim bouts. Temporal characteristics of these
responses are suggestive of a general role for the larval zebrafish cerebellum in
controlling swimming. Climbing fibers encoded both visual and motor signals but
did not appear to encode signals that could be used to adjust OMR gain, such as
retinal slip. Finally, the observation of diverse relationships between simple
spikes and climbing fiber responses in individual Purkinje cells highlights the
importance of distinguishing between these two types of activity in calcium
imaging experiments.
PMID- 27512019
TI - White matter and cognition: making the connection.
AB - Whereas the cerebral cortex has long been regarded by neuroscientists as the
major locus of cognitive function, the white matter of the brain is increasingly
recognized as equally critical for cognition. White matter comprises half of the
brain, has expanded more than gray matter in evolution, and forms an
indispensable component of distributed neural networks that subserve
neurobehavioral operations. White matter tracts mediate the essential
connectivity by which human behavior is organized, working in concert with gray
matter to enable the extraordinary repertoire of human cognitive capacities. In
this review, we present evidence from behavioral neurology that white matter
lesions regularly disturb cognition, consider the role of white matter in the
physiology of distributed neural networks, develop the hypothesis that white
matter dysfunction is relevant to neurodegenerative disorders, including
Alzheimer's disease and the newly described entity chronic traumatic
encephalopathy, and discuss emerging concepts regarding the prevention and
treatment of cognitive dysfunction associated with white matter disorders.
Investigation of the role of white matter in cognition has yielded many valuable
insights and promises to expand understanding of normal brain structure and
function, improve the treatment of many neurobehavioral disorders, and disclose
new opportunities for research on many challenging problems facing medicine and
society.
PMID- 27512020
TI - The destination defines the journey: an examination of the kinematics of hand-to
mouth movements.
AB - Long-train electrical stimulation of the motor and premotor cortices of nonhuman
primates can produce either hand-to-mouth or grasp-to-inspect movements,
depending on the precise location of stimulation. Furthermore, single-neuron
recording studies identify discrete neuronal populations in the inferior parietal
and ventral premotor cortices that respond uniquely to either grasp-to-eat or
grasp-to-place movements, despite their identical mechanistic requirements. These
studies demonstrate that the macaque motor cortex is organized around producing
functional, goal-oriented movements, rather than simply fulfilling muscular
prerequisites of action. In humans, right-handed hand-to-mouth movements have a
unique kinematic signature; smaller maximum grip apertures are produced when
grasping to eat than when grasping to place identical targets. This is evidence
that the motor cortex in humans is also organized around producing functional
movements. However, in both macaques and humans, grasp-to-eat/hand-to-mouth
movements have always been elicited using edible targets and have (necessarily)
been paired with mouth movement. It is therefore unknown whether the kinematic
distinction is a natural result of grasping food and/or is simply attributable to
concurrent opening of the mouth while grasping. In experiment 1, we used goal
differentiated grasping tasks, directed toward edible and inedible targets, to
show that the unique kinematic signature is present even with inedible targets.
In experiment 2, we used the same goal-differentiated grasping tasks, either
coupled with or divorced from an open-mouth movement, to show that the signature
is not attributable merely to a planned opening of the mouth during the grasp.
These results are discussed in relation to the role of hand-to-mouth movements in
human development, independently of grasp-to-eat behavior.
PMID- 27512021
TI - Contextual processing in unpredictable auditory environments: the limited
resource model of auditory refractoriness in the rhesus.
AB - Auditory refractoriness refers to the finding of smaller electroencephalographic
(EEG) responses to tones preceded by shorter periods of silence. To date, its
physiological mechanisms remain unclear, limiting the insights gained from
findings of abnormal refractoriness in individuals with schizophrenia. To resolve
this roadblock, we studied auditory refractoriness in the rhesus, one of the most
important animal models of auditory function, using grids of up to 32 chronically
implanted cranial EEG electrodes. Four macaques passively listened to sounds
whose identity and timing was random, thus preventing animals from forming valid
predictions about upcoming sounds. Stimulus onset asynchrony ranged between 0.2
and 12.8 s, thus encompassing the clinically relevant timescale of
refractoriness. Our results show refractoriness in all 8 previously identified
middle- and long-latency components that peaked between 14 and 170 ms after tone
onset. Refractoriness may reflect the formation and gradual decay of a basic
sensory memory trace that may be mirrored by the expenditure and gradual recovery
of a limited physiological resource that determines generator excitability. For
all 8 components, results were consistent with the assumption that processing of
each tone expends ~65% of the available resource. Differences between components
are caused by how quickly the resource recovers. Recovery time constants of
different components ranged between 0.5 and 2 s. This work provides a solid
conceptual, methodological, and computational foundation to dissect the
physiological mechanisms of auditory refractoriness in the rhesus. Such knowledge
may, in turn, help develop novel pharmacological, mechanism-targeted
interventions.
PMID- 27512022
TI - Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron
excitability by modulators of KCNQ/Kv7 channels.
AB - KCNQ/Kv7 channels form a slow noninactivating K+ current, also known as the M
current. They activate in the subthreshold range of membrane potentials and
regulate different aspects of excitability in neurons of the central nervous
system. In spinal motoneurons (MNs), KCNQ/Kv7 channels have been identified in
the somata, axonal initial segment, and nodes of Ranvier, where they generate a
slow, noninactivating, K+ current sensitive to both muscarinic receptor-mediated
inhibition and KCNQ/Kv7 channel blockers. In this study, we thoroughly
reevaluated the function of up- and downregulation of KCNQ/Kv7 channels in mouse
immature spinal MNs. Using electrophysiological techniques together with specific
pharmacological modulators of the activity of KCNQ/Kv7 channels, we show that
enhancement of the activity of these channels decreases the excitability of
spinal MNs in mouse neonates. This action on MNs results from a combination of
hyperpolarization of the resting membrane potential, a decrease in the input
resistance, and depolarization of the voltage threshold. On the other hand, the
effect of inhibition of KCNQ/Kv7 channels suggested that these channels play a
limited role in regulating basal excitability. Computer simulations confirmed
that pharmacological enhancement of KCNQ/Kv7 channel activity decreases
excitability and also suggested that the effects of inhibition of KCNQ/Kv7
channels on the excitability of spinal MNs do not depend on a direct effect in
these neurons but likely on spinal cord synaptic partners. These results indicate
that KCNQ/Kv7 channels have a fundamental role in the modulation of the
excitability of spinal MNs acting both in these neurons and in their local
presynaptic partners.
PMID- 27512029
TI - Newsletter.
PMID- 27512023
TI - Sciatic nerve stimulation activates the retrotrapezoid nucleus in anesthetized
rats.
AB - Retrotrapezoid nucleus (RTN) neurons sustain breathing automaticity. These
neurons have chemoreceptor properties, but their firing is also regulated by
multiple synaptic inputs of uncertain function. Here we test whether RTN neurons,
like neighboring presympathetic neurons, are excited by somatic afferent
stimulation. Experiments were performed in Inactin-anesthetized, bilaterally
vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats. End
expiratory CO2 (eeCO2) was varied between 4% and 10% to modify rate and amplitude
of phrenic nerve discharge (PND). RTN and presympathetic neurons were recorded
extracellularly below the facial motor nucleus with established criteria. Sciatic
nerve stimulation (SNstim, 1 ms, 0.5 Hz) slightly increased blood pressure (6.6
+/- 1.6 mmHg) and heart rate and, at low eeCO2 (<5.5%), entrained PND. Ipsi- and
contralateral SNstim produced the known biphasic activation of presympathetic
neurons. SNstim evoked a similar but weaker biphasic response in up to 67% of RTN
neurons and monophasic excitation in the rest. At low eeCO2, RTN neurons were
silent and responded more weakly to SNstim than at high eeCO2 RTN neuron firing
was respiratory modulated to various degrees. The phasic activation of RTN
neurons elicited by SNstim was virtually unchanged at high eeCO2 when PND
entrainment to the stimulus was disrupted. Thus RTN neuron response to SNstim did
not result from entrainment to the central pattern generator. Overall, SNstim
shifted the relationship between RTN firing and eeCO2 upward. In conclusion,
somatic afferent stimulation increases RTN neuron firing probability without
altering their response to CO2. This pathway may contribute to the hyperpnea
triggered by nociception, exercise (muscle metabotropic reflex), or hyperthermia.
PMID- 27512032
TI - Reply to Willis: Powerful predictions of biodiversity from ecological models and
scaling laws.
PMID- 27512033
TI - Extrapolating abundance curves has no predictive power for estimating microbial
biodiversity.
PMID- 27512034
TI - Microtubule-microtubule sliding by kinesin-1 is essential for normal cytoplasmic
streaming in Drosophila oocytes.
AB - Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk
cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and
proteins deposited by the nurse cells across the oocyte. This movement is driven
by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1
heavy chain (KHC) can transport one microtubule on another microtubule, thus
driving microtubule-microtubule sliding in multiple cell types. To study the role
of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that
is deficient in microtubule sliding but able to transport a majority of cargoes.
We demonstrated that streaming is reduced by genomic replacement of wild-type Khc
with this sliding-deficient mutant. Streaming can be fully rescued by wild-type
KHC and partially rescued by a chimeric motor that cannot move organelles but is
active in microtubule sliding. Consistent with these data, we identified two
populations of microtubules in fast-streaming oocytes: a network of stable
microtubules anchored to the actin cortex and free cytoplasmic microtubules that
moved in the ooplasm. We further demonstrated that the reduced streaming in
sliding-deficient oocytes resulted in posterior determination defects. Together,
we propose that kinesin-1 slides free cytoplasmic microtubules against cortically
immobilized microtubules, generating forces that contribute to cytoplasmic
streaming and are essential for the refinement of posterior determinants.
PMID- 27512035
TI - Cracking the allosteric code of NMR chemical shifts.
PMID- 27512036
TI - The heart in sickle cell disease, a model for heart failure with preserved
ejection fraction.
PMID- 27512037
TI - Critically jammed.
PMID- 27512038
TI - Critically evaluating the theory and performance of Bayesian analysis of
macroevolutionary mixtures.
AB - Bayesian analysis of macroevolutionary mixtures (BAMM) has recently taken the
study of lineage diversification by storm. BAMM estimates the diversification
rate parameters (speciation and extinction) for every branch of a study phylogeny
and infers the number and location of diversification-rate shifts across branches
of a tree. Our evaluation of BAMM reveals two major theoretical errors: (i) the
likelihood function (which estimates the model parameters from the data) is
incorrect, and (ii) the compound Poisson process prior model (which describes the
prior distribution of diversification-rate shifts across branches) is incoherent.
Using simulation, we demonstrate that these theoretical issues cause statistical
pathologies; posterior estimates of the number of diversification-rate shifts are
strongly influenced by the assumed prior, and estimates of diversification-rate
parameters are unreliable. Moreover, the inability to correctly compute the
likelihood or to correctly specify the prior for rate-variable trees precludes
the use of Bayesian approaches for testing hypotheses regarding the number and
location of diversification-rate shifts using BAMM.
PMID- 27512039
TI - miR-322/-503 cluster is expressed in the earliest cardiac progenitor cells and
drives cardiomyocyte specification.
AB - Understanding the mechanisms of early cardiac fate determination may lead to
better approaches in promoting heart regeneration. We used a mesoderm posterior 1
(Mesp1)-Cre/Rosa26-EYFP reporter system to identify microRNAs (miRNAs) enriched
in early cardiac progenitor cells. Most of these miRNA genes bear MESP1-binding
sites and active histone signatures. In a calcium transient-based screening
assay, we identified miRNAs that may promote the cardiomyocyte program. An X
chromosome miRNA cluster, miR-322/-503, is the most enriched in the Mesp1 lineage
and is the most potent in the screening assay. It is specifically expressed in
the looping heart. Ectopic miR-322/-503 mimicking the endogenous temporal
patterns specifically drives a cardiomyocyte program while inhibiting neural
lineages, likely by targeting the RNA-binding protein CUG-binding protein Elav
like family member 1 (Celf1). Thus, early miRNAs in lineage-committed cells may
play powerful roles in cell-fate determination by cross-suppressing other
lineages. miRNAs identified in this study, especially miR-322/-503, are potent
regulators of early cardiac fate.
PMID- 27512040
TI - Spontaneous eyelid closures link vigilance fluctuation with fMRI dynamic
connectivity states.
AB - Fluctuations in resting-state functional connectivity occur but their behavioral
significance remains unclear, largely because correlating behavioral state with
dynamic functional connectivity states (DCS) engages probes that disrupt the very
behavioral state we seek to observe. Observing spontaneous eyelid closures
following sleep deprivation permits nonintrusive arousal monitoring. During
periods of low arousal dominated by eyelid closures, sliding-window correlation
analysis uncovered a DCS associated with reduced within-network functional
connectivity of default mode and dorsal/ventral attention networks, as well as
reduced anticorrelation between these networks. Conversely, during periods when
participants' eyelids were wide open, a second DCS was associated with less
decoupling between the visual network and higher-order cognitive networks that
included dorsal/ventral attention and default mode networks. In subcortical
structures, eyelid closures were associated with increased connectivity between
the striatum and thalamus with the ventral attention network, and greater
anticorrelation with the dorsal attention network. When applied to task-based
fMRI data, these two DCS predicted interindividual differences in frequency of
behavioral lapsing and intraindividual temporal fluctuations in response speed.
These findings with participants who underwent a night of total sleep deprivation
were replicated in an independent dataset involving partially sleep-deprived
participants. Fluctuations in functional connectivity thus appear to be clearly
associated with changes in arousal.
PMID- 27512041
TI - Scaling ansatz for the jamming transition.
AB - We propose a Widom-like scaling ansatz for the critical jamming transition. Our
ansatz for the elastic energy shows that the scaling of the energy, compressive
strain, shear strain, system size, pressure, shear stress, bulk modulus, and
shear modulus are all related to each other via scaling relations, with only
three independent scaling exponents. We extract the values of these exponents
from already known numerical or theoretical results, and we numerically verify
the resulting predictions of the scaling theory for the energy and residual shear
stress. We also derive a scaling relation between pressure and residual shear
stress that yields insight into why the shear and bulk moduli scale differently.
Our theory shows that the jamming transition exhibits an emergent scale
invariance, setting the stage for the potential development of a renormalization
group theory for jamming.
PMID- 27512042
TI - Hydrodynamic theory of thermoelectric transport and negative magnetoresistance in
Weyl semimetals.
AB - We present a theory of thermoelectric transport in weakly disordered Weyl
semimetals where the electron-electron scattering time is faster than the
electron-impurity scattering time. Our hydrodynamic theory consists of
relativistic fluids at each Weyl node, coupled together by perturbatively small
intervalley scattering, and long-range Coulomb interactions. The conductivity
matrix of our theory is Onsager reciprocal and positive semidefinite. In addition
to the usual axial anomaly, we account for the effects of a distinct, axial
gravitational anomaly expected to be present in Weyl semimetals. Negative thermal
magnetoresistance is a sharp, experimentally accessible signature of this axial
gravitational anomaly, even beyond the hydrodynamic limit.
PMID- 27512043
TI - Coiled-coil destabilizing residues in the group A Streptococcus M1 protein are
required for functional interaction.
AB - The sequences of M proteins, the major surface-associated virulence factors of
the widespread bacterial pathogen group A Streptococcus, are antigenically
variable but have in common a strong propensity to form coiled coils.
Paradoxically, these sequences are also replete with coiled-coil destabilizing
residues. These features are evident in the irregular coiled-coil structure and
thermal instability of M proteins. We present an explanation for this paradox
through studies of the B repeats of the medically important M1 protein. The B
repeats are required for interaction of M1 with fibrinogen (Fg) and consequent
proinflammatory activation. The B repeats sample multiple conformations,
including intrinsically disordered, dissociated, as well as two alternate coiled
coil conformations: a Fg-nonbinding register 1 and a Fg-binding register 2.
Stabilization of M1 in the Fg-nonbinding register 1 resulted in attenuation of Fg
binding as expected, but counterintuitively, so did stabilization in the Fg
binding register 2. Strikingly, these register-stabilized M1 proteins gained the
ability to bind Fg when they were destabilized by a chaotrope. These results
indicate that M1 stability is antithetical to Fg interaction and that M1
conformational dynamics, as specified by destabilizing residues, are essential
for interaction. A "capture-and-collapse" model of association accounts for these
observations, in which M1 captures Fg through a dynamic conformation and then
collapses into a register 2-coiled coil as a result of stabilization provided by
binding energy. Our results support the general conclusion that destabilizing
residues are evolutionarily conserved in M proteins to enable functional
interactions necessary for pathogenesis.
PMID- 27512044
TI - Ultrapotent vinblastines in which added molecular complexity further disrupts the
target tubulin dimer-dimer interface.
AB - Approaches to improving the biological properties of natural products typically
strive to modify their structures to identify the essential pharmacophore, or
make functional group changes to improve biological target affinity or functional
activity, change physical properties, enhance stability, or introduce
conformational constraints. Aside from accessible semisynthetic modifications of
existing functional groups, rarely does one consider using chemical synthesis to
add molecular complexity to the natural product. In part, this may be attributed
to the added challenge intrinsic in the synthesis of an even more complex
compound. Herein, we report synthetically derived, structurally more complex
vinblastines inaccessible from the natural product itself that are a stunning 100
fold more active (IC50 values, 50-75 pM vs. 7 nM; HCT116), and that are now
accessible because of advances in the total synthesis of the natural product. The
newly discovered ultrapotent vinblastines, which may look highly unusual upon
first inspection, bind tubulin with much higher affinity and likely further
disrupt the tubulin head-to-tail alpha/beta dimer-dimer interaction by virtue of
the strategic placement of an added conformationally well-defined, rigid, and
extended C20' urea along the adjacent continuing protein-protein interface. In
this case, the added molecular complexity was used to markedly enhance target
binding and functional biological activity (100-fold), and likely represents a
general approach to improving the properties of other natural products targeting
a protein-protein interaction.
PMID- 27512045
TI - Profile of Nancy C. Andrews.
PMID- 27512046
TI - Role of kinesin-1-based microtubule sliding in Drosophila nervous system
development.
AB - The plus-end microtubule (MT) motor kinesin-1 is essential for normal
development, with key roles in the nervous system. Kinesin-1 drives axonal
transport of membrane cargoes to fulfill the metabolic needs of neurons and
maintain synapses. We have previously demonstrated that kinesin-1, in addition to
its well-established role in organelle transport, can drive MT-MT sliding by
transporting "cargo" MTs along "track" MTs, resulting in dramatic cell shape
changes. The mechanism and physiological relevance of this MT sliding are
unclear. In addition to its motor domain, kinesin-1 contains a second MT-binding
site, located at the C terminus of the heavy chain. Here, we mutated this C
terminal MT-binding site such that the ability of kinesin-1 to slide MTs is
significantly compromised, whereas cargo transport is unaffected. We introduced
this mutation into the genomic locus of kinesin-1 heavy chain (KHC), generating
the Khc(mutA) allele. Khc(mutA) neurons displayed significant MT sliding defects
while maintaining normal transport of many cargoes. Using this mutant, we
demonstrated that MT sliding is required for axon and dendrite outgrowth in vivo.
Consistent with these results, Khc(mutA) flies displayed severe locomotion and
viability defects. To test the role of MT sliding further, we engineered a
chimeric motor that actively slides MTs but cannot transport organelles.
Activation of MT sliding in Khc(mutA) neurons using this chimeric motor rescued
axon outgrowth in cultured neurons and in vivo, firmly establishing the role of
sliding in axon outgrowth. These results demonstrate that MT sliding by kinesin-1
is an essential biological phenomenon required for neuronal morphogenesis and
normal nervous system development.
PMID- 27512048
TI - Reply to Inbar: Contextual sensitivity helps explain the reproducibility gap
between social and cognitive psychology.
PMID- 27512047
TI - Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell
disease.
AB - Hydroxyurea (HU) has been used clinically to reduce the frequency of painful
crisis and the need for blood transfusion in sickle cell disease (SCD) patients.
However, the mechanisms underlying such beneficial effects of HU treatment are
still not fully understood. Studies have indicated a weak correlation between
clinical outcome and molecular markers, and the scientific quest to develop
companion biophysical markers have mostly targeted studies of blood properties
under hypoxia. Using a common-path interferometric technique, we measure
biomechanical and morphological properties of individual red blood cells in SCD
patients as a function of cell density, and investigate the correlation of these
biophysical properties with drug intake as well as other clinically measured
parameters. Our results show that patient-specific HU effects on the cellular
biophysical properties are detectable at normoxia, and that these properties are
strongly correlated with the clinically measured mean cellular volume rather than
fetal hemoglobin level.
PMID- 27512049
TI - Association between contextual dependence and replicability in psychology may be
spurious.
PMID- 27512050
TI - Cognitive impairment among patients with multiple sclerosis: associations with
employment and quality of life.
AB - OBJECTIVES: To explore the relationship between cognitive impairment and
conventional measures of disability in multiple sclerosis (MS), quality of life
(QOL) and employment status using the brief international cognitive assessment
for multiple sclerosis (BICAMS) in the routine outpatient clinic. METHODS: 62
patients with MS were assessed on the BICAMS test battery for cognitive
impairment. Data were obtained on employment status and a number of
questionnaires completed including fatigue severity score, multiple sclerosis
neuropsychological questionnaire, hospital anxiety and depression scale, the
functional assessment of multiple sclerosis (FAMS) as well as on the EuroQOL five
dimension questionnaire (EQ-5D). Other assessments include the patient activation
measure and unidimensional self-efficacy scale for multiple sclerosis. RESULTS:
Cognitive assessment revealed 44 subjects (65%) had evidence of cognitive
impairment on formal testing. In comparison with patients without evidence of
cognitive impairment, cognitively impaired patients exhibited significantly
higher rates of unemployment (p=0.009). The symbol digits modalities test was the
most significant predictor of unemployment. Cognitive impairment was associated
with lower QOL scores on the FAMS (p=0.001) and EQ-5D (p<0.001). CONCLUSIONS:
BICAMS provides a sensitive and easy to administer screening test for cognitive
impairment within the outpatient setting. Cognitive impairment is common in our
cohort of patients with MS attending outpatients and appears to be associated
with increased rates of unemployment and lower measures of QOL.
PMID- 27512051
TI - Patterns, predictors and effects of texting intervention on physical activity in
CHD - insights from the TEXT ME randomized clinical trial.
AB - BACKGROUND: Mobile phone text message interventions are used to support behaviour
change including physical activity, but we have less insight into how these
interventions work and what factors predict response. AIMS: To study the effect
of TEXT ME (Tobacco EXercise and dieT Messages) text message intervention on
physical activity domains, consistency of effects across sub-groups and its
additive value in patients that received traditional cardiac rehabilitation
programme. METHODS: This is a secondary analysis of the TEXT ME, a randomized
clinical trial of lifestyle-focused text message intervention compared with usual
care in patients with coronary heart disease. A quarter of the messages were
designed specifically to encourage physical activity. Sedentary time and physical
activity were assessed using the Global Physical Activity Questionnaire. RESULTS:
At baseline, 85% of the 710 participants reported low physical activity levels.
At six months, compared with controls, the intervention arm reported higher
recreational physical activity (471 vs. 307 metabolic equivalent-min/week, p =
0.001) and travel physical activity (230 vs. 128 MET-min/week, p = 0.002),
similar work-related physical activity and lower sedentary times (494 vs. 587
min, p < 0.001). Male gender, high baseline physical activity, cardiac
rehabilitation participation and text message intervention predicted physically
active status at six months. Subjects that received both cardiac rehabilitation
and text messaging intervention were more likely to achieve target physical
activity levels compared with cardiac rehabilitation alone (odds ratio 7.07 vs.
1.80, p < 0.001). CONCLUSIONS: The TEXT ME intervention improved recreational and
travel physical activity, reduced sedentary times but had no effects on work
related physical activity. It had incremental benefits at achieving target
physical activity levels even in patients participating in the traditional
cardiac rehabilitation programme.
PMID- 27512052
TI - The blood pressure-lowering effect of a single bout of resistance exercise: A
systematic review and meta-analysis of randomised controlled trials.
AB - BACKGROUND: Current exercise guidelines recommend aerobic types of exercises on
most days of the week, supplemented with dynamic resistance exercise twice
weekly. Whereas the blood pressure (BP)-lowering effects of a single session of
aerobic exercise have been well studied, less is known about the hypotensive
effect of a single bout of resistance exercise. OBJECTIVES: To evaluate the
transient effect of resistance exercise on BP by means of meta-analytic
techniques. METHODS: A systematic electronic search in Medline, Scientific
Electronic Library Online (SciELO), Latin American and Caribbean Health Sciences
Literature (LILACS), Elton B Stephens Company (EBSCO), EMBASE and SPORTDiscus was
completed in March 2015 identifying randomised controlled trials investigating
the effect of a single bout of resistance exercise on resting or ambulatory BP in
healthy adults. A subsequent meta-analysis was performed. RESULTS: The meta
analysis involved 30 studies, 81 interventions and 646 participants (normotensive
(n = 505) or hypertensive (n = 141)). A single bout of resistance exercise
elicited small-to-moderate reductions in office systolic BP at 60 minutes
postexercise [-3.3 (-4.0 to -2.6)/-2.7 (-3.2 to -2.1) mmHg (CI 95%)], 90 minutes
postexercise [-5.3 (-8.5 to -2.1)/-4.7 (-6.9 to -2.4) mmHg (CI 95%)] and in 24
hour ambulatory BP [-1.7 (-2.8 to -0.67)/-1.2 (-2.4 to -0.022) mmHg (CI 95%)]
compared to a control session. The reduction in office BP was more pronounced in
hypertensive compared to normotensive individuals (p < 0.01), when using larger
muscle groups (p < 0.05) and when participants were recovering in the supine
position (p < 0.01). CONCLUSION: A single bout of resistance exercise can have a
BP-lowering effect that last for up to 24 hours. Supine recovery and the use of
larger muscle groups resulted in greater BP reductions after resistance exercise.
PMID- 27512053
TI - Refined interpretation of exercise ECG testing: Opportunities for a comeback in
the era of expanding advanced cardiac imaging technologies?
PMID- 27512054
TI - The calcium-dependent protein kinase RcCDPK2 phosphorylates sucrose synthase at
Ser11 in developing castor oil seeds.
AB - Imported sucrose is cleaved by sucrose synthase (SUS) as a critical initial
reaction in the biosynthesis of storage end-products by developing seeds.
Although SUS is phosphorylated at a conserved seryl residue by an apparent CDPK
(Ca2+-dependent protein kinase) in diverse plant tissues, the functions and
mechanistic details of this process remain obscure. Thus, the native CDPK that
phosphorylates RcSUS1 (Ricinus communis SUS1) at Ser11 in developing COS (castor
oil seeds) was highly purified and identified as RcCDPK2 by MS/MS. Purified
RcSUS1-K (-kinase) and heterologously expressed RcCDPK2 catalyzed Ca2+-dependent
Ser11 phosphorylation of RcSUS1 and its corresponding dephosphopeptide, while
exhibiting a high affinity for free Ca2+ ions [K0.5(Ca2+) < 0.4 uM]. RcSUS1-K
activity, RcCDPK2 expression, and RcSUS1 Ser11 phosphorylation peaked during
early COS development and then declined in parallel. The elimination of sucrose
import via fruit excision triggered RcSUS1 dephosphorylation but did not alter
RcSUS1-K activity, suggesting a link between sucrose signaling and
posttranslational RcCDPK2 control. Both RcCDPK2-mCherry and RcSUS1-EYFP co
localized throughout the cytosol when transiently co-expressed in tobacco
suspension cells, although RcCDPK2-mCherry was also partially localized to the
nucleus. Subcellular fractionation revealed that ~20% of RcSUS1-K activity
associates with microsomal membranes in developing COS, as does RcSUS1. In
contrast with RcCDPK1, which catalyzes inhibitory phosphorylation of COS
bacterial-type phosphoenolpyruvate carboxylase at Ser451, RcCDPK2 exhibited broad
substrate specificity, a wide pH-activity profile centered at pH 8.5, and
insensitivity to metabolite effectors or thiol redox status. Our combined results
indicate a possible link between cytosolic Ca2+-signaling and the control of
photosynthate partitioning during COS development.
PMID- 27512055
TI - Antigenic Fingerprinting of Antibody Response in Humans following Exposure to
Highly Pathogenic H7N7 Avian Influenza Virus: Evidence for Anti-PA-X Antibodies.
AB - Infections with H7 highly pathogenic avian influenza (HPAI) viruses remain a
major public health concern. Adaptation of low-pathogenic H7N7 to highly
pathogenic H7N7 in Europe in 2015 raised further alarm for a potential pandemic.
An in-depth understanding of antibody responses to HPAI H7 virus following
infection in humans could provide important insight into virus gene expression as
well as define key protective and serodiagnostic targets. Here we used whole
genome gene fragment phage display libraries (GFPDLs) expressing peptides of 15
to 350 amino acids across the complete genome of the HPAI H7N7
A/Netherlands/33/03 virus. The hemagglutinin (HA) antibody epitope repertoires of
15 H7N7-exposed humans identified clear differences between individuals with no
hemagglutination inhibition (HI) titers (<1:10) and those with HI titers of
>1:40. Several potentially protective H7N7 epitopes close to the HA receptor
binding domain (RBD) and neuraminidase (NA) catalytic site were identified.
Surface plasmon resonance (SPR) analysis identified a strong correlation between
HA1 (but not HA2) binding antibodies and H7N7 HI titers. A proportion of HA1
binding in plasma was contributed by IgA antibodies. Antibodies against the N7
neuraminidase were less frequent but targeted sites close to the sialic acid
binding site. Importantly, we identified strong antibody reactivity against PA-X,
a putative virulence factor, in most H7N7-exposed individuals, providing the
first evidence for in vivo expression of PA-X and its recognition by the immune
system during human influenza A virus infection. This knowledge can help inform
the development and selection of the most effective countermeasures for
prophylactic as well as therapeutic treatments of HPAI H7N7 avian influenza
virus. IMPORTANCE: An outbreak of pathogenic H7N7 virus occurred in poultry farms
in The Netherlands in 2003. Severe outcome included conjunctivitis, influenza
like illness, and one lethal infection. In this study, we investigated
convalescent-phase sera from H7N7-exposed individuals by using a whole-genome
phage display library (H7N7-GFPDL) to explore the complete repertoire of post
H7N7-exposure antibodies. PA-X is a recently identified influenza virus virulence
protein generated by ribosomal frameshifting in segment 3 of influenza virus
coding for PA. However, PA-X expression during influenza virus infection in
humans is unknown. We identified strong antibody reactivity against PA-X in most
H7N7-exposed individuals (but not in unexposed adults), providing the first
evidence for in vivo expression of PA-X and its recognition by the immune system
during human infection with pathogenic H7N7 avian influenza virus.
PMID- 27512056
TI - Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T
Cells to the Lung.
AB - Pigs are natural hosts for influenza A viruses and play a critical role in
influenza epidemiology. However, little is known about their influenza-evoked T
cell response. We performed a thorough analysis of both the local and systemic T
cell response in influenza virus-infected pigs, addressing kinetics and phenotype
as well as multifunctionality (gamma interferon [IFN-gamma], tumor necrosis
factor alpha [TNF-alpha], and interleukin-2 [IL-2]) and cross-reactivity. A total
of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus
(FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and
blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks
p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in
proliferating (Ki-67(+)) CD8(+) T cells with an early effector phenotype
(perforin(+) CD27(+)) at day 6 p.i. Low frequencies of influenza virus-specific
IFN-gamma-producing CD4(+) and CD8(+) T cells could be detected in the lung as
early as 4 days p.i. On consecutive days, influenza virus-specific CD4(+) and
CD8(+) T cells produced mainly IFN-gamma and/or TNF-alpha, reaching peak
frequencies around day 9 p.i., which were up to 30-fold higher in the lung than
in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4(+) and CD8(+)
memory T cells had accumulated in lung tissue. These cells showed diverse
cytokine profiles and in vitro reactivity against heterologous influenza virus
strains, all of which supports their potential to combat heterologous influenza
virus infections in pigs. IMPORTANCE: Pigs not only are a suitable large-animal
model for human influenza virus infection and vaccine development but also play a
central role in the emergence of new pandemic strains. Although promising
candidate universal vaccines are tested in pigs and local T cells are the major
correlate of heterologous control, detailed and targeted analyses of T-cell
responses at the site of infection are scarce. With the present study, we provide
the first detailed characterization of magnitude, kinetics, and phenotype of
specific T cells recruited to the lungs of influenza virus-infected pigs, and we
could demonstrate multifunctionality, cross-reactivity, and memory formation of
these cells. This, and ensuing work in the pig, will strengthen the position of
this species as a large-animal model for human influenza virus infection and will
immediately benefit vaccine development for improved control of influenza virus
infections in pigs.
PMID- 27512058
TI - Graf1 Controls the Growth of Human Parainfluenza Virus Type 2 through
Inactivation of RhoA Signaling.
AB - Rho GTPases are involved in a variety of cellular activities and are regulated by
guanine nucleotide exchange factors and GTPase-activating proteins (GAPs). We
found that the activation of Rho GTPases by lysophosphatidic acid promotes the
growth of human parainfluenza virus type 2 (hPIV-2). Furthermore, hPIV-2
infection causes activation of RhoA, a Rho GTPase. We hypothesized that Graf1
(also known as ARHGAP26), a GAP, regulates hPIV-2 growth by controlling RhoA
signaling. Immunofluorescence analysis showed that hPIV-2 infection altered Graf1
localization from a homogenous distribution within the cytoplasm to granules.
Graf1 colocalized with hPIV-2 P, NP, and L proteins. Graf1 interacts with P and V
proteins via their N-terminal common region, and the C-terminal Src homology 3
domain-containing region of Graf1 is important for these interactions. In HEK293
cells constitutively expressing Graf1, hPIV-2 growth was inhibited, and RhoA
activation was not observed during hPIV-2 infection. In contrast, Graf1 knockdown
restored hPIV-2 growth and RhoA activation. Overexpression of hPIV-2 P and V
proteins enhanced hPIV-2-induced RhoA activation. These results collectively
suggested that hPIV-2 P and V proteins enhanced hPIV-2 growth by binding to Graf1
and that Graf1 inhibits hPIV-2 growth through RhoA inactivation. IMPORTANCE:
Robust growth of hPIV-2 requires Rho activation. hPIV-2 infection causes RhoA
activation, which is suppressed by Graf1. Graf1 colocalizes with viral RNP (vRNP)
in hPIV-2-infected cells. We found that Graf1 interacts with hPIV-2 P and V
proteins. We also identified regions in these proteins which are important for
this interaction. hPIV-2 P and V proteins enhanced the hPIV-2 growth via binding
to Graf1, while Graf1 inhibited hPIV-2 growth through RhoA inactivation.
PMID- 27512057
TI - Japanese Macaque Rhadinovirus Encodes a Viral MicroRNA Mimic of the miR-17
Family.
AB - Japanese macaque (JM) rhadinovirus (JMRV) is a novel, gamma-2 herpesvirus that
was recently isolated from JM with inflammatory demyelinating encephalomyelitis
(JME). JME is a spontaneous and chronic disease with clinical characteristics and
immunohistopathology comparable to those of multiple sclerosis in humans. Little
is known about the molecular biology of JMRV. Here, we sought to identify and
characterize the small RNAs expressed during lytic JMRV infection using deep
sequencing. Fifteen novel viral microRNAs (miRNAs) were identified in JMRV
infected fibroblasts, all of which were readily detectable by 24 h postinfection
and accumulated to high levels by 72 h. Sequence comparisons to human Kaposi's
sarcoma-associated herpesvirus (KSHV) miRNAs revealed several viral miRNA
homologs. To functionally characterize JMRV miRNAs, we screened for their effects
on nuclear factor kappa B (NF-kappaB) signaling in the presence of two
proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and
interleukin-1beta (IL-1beta). Multiple JMRV miRNAs suppressed cytokine-induced NF
kappaB activation. One of these miRNAs, miR-J8, has seed sequence homology to
members of the cellular miR-17/20/106 and miR-373 families, which are key players
in cell cycle regulation as well as inflammation. Using reporters, we show that
miR-J8 can target 3' untranslated regions (UTRs) with miR-17-5p or miR-20a
cognate sites. Our studies implicate JMRV miRNAs in the suppression of innate
antiviral immune responses, which is an emerging feature of many viral miRNAs.
IMPORTANCE: Gammaherpesviruses are associated with multiple diseases linked to
immunosuppression and inflammation, including AIDS-related cancers and autoimmune
diseases. JMRV is a recently identified herpesvirus that has been linked to JME,
an inflammatory demyelinating disease in Japanese macaques that mimics multiple
sclerosis. There are few large-animal models for gammaherpesvirus-associated
pathogenesis. Here, we provide the first experimental evidence of JMRV miRNAs in
vitro and demonstrate that one of these viral miRNAs can mimic the activity of
the cellular miR-17/20/106 family. Our work provides unique insight into the
roles of viral miRNAs during rhadinovirus infection and provides an important
step toward understanding viral miRNA function in a nonhuman primate model
system.
PMID- 27512059
TI - Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of
Their Virulent Relatives.
AB - Two closely related caliciviruses cocirculate in Australia: rabbit hemorrhagic
disease virus (RHDV) and rabbit calicivirus Australia 1 (RCV-A1). RCV-A1 causes
benign enteric infections in the European rabbit (Oryctolagus cuniculus) in
Australia and New Zealand, while its close relative RHDV causes a highly
pathogenic infection of the liver in the same host. The comparison of these
viruses provides important information on the nature and trajectory of virulence
evolution, particularly as highly virulent strains of RHDV may have evolved from
nonpathogenic ancestors such as RCV-A1. To determine the evolution of RCV-A1 we
sequenced the full-length genomes of 44 RCV-A1 samples isolated from healthy
rabbits and compared key evolutionary parameters to those of its virulent
relative, RHDV. Despite their marked differences in pathogenicity and tissue
tropism, RCV-A1 and RHDV have evolved in a very similar manner. Both viruses have
evolved at broadly similar rates, suggesting that their dynamics are largely
shaped by high background mutation rates, and both exhibit occasional
recombination and an evolutionary environment dominated by purifying selection.
In addition, our comparative analysis revealed that there have been multiple
changes in both virulence and tissue tropism in the evolutionary history of these
and related viruses. Finally, these new genomic data suggest that either RCV-A1
was introduced into Australia after the introduction of myxoma virus as a
biocontrol agent in 1950 or there was drastic reduction of the rabbit population,
and hence of RCV-A1 genetic diversity, perhaps coincident with the emergence of
myxoma virus. IMPORTANCE: The comparison of closely related viruses that differ
profoundly in propensity to cause disease in their hosts offers a powerful
opportunity to reveal the causes of changes in virulence and to study how such
changes alter the evolutionary dynamics of these pathogens. Here we describe such
a novel comparison involving two closely related RNA viruses that cocirculate in
Australia, the highly virulent rabbit hemorrhagic disease virus (RHDV) and the
nonpathogenic rabbit calicivirus Australia 1 (RCV-A1). Both viruses infect the
European rabbit, but they differ in virulence, tissue tropism, and mechanisms of
transmission. Surprisingly, and despite these fundamental differences, RCV-A1 and
RHDV have evolved at very similar (high) rates and with strong purifying
selection. Furthermore, candidate key mutations were identified that may play a
role in virulence and/or tissue tropism and therefore warrant further
investigation.
PMID- 27512060
TI - RIG-I-Mediated STING Upregulation Restricts Herpes Simplex Virus 1 Infection.
AB - STING has emerged in recent years as a key player in orchestrating innate immune
responses to cytosolic DNA and RNA derived from pathogens. However, the
regulation of STING still remains poorly defined. In the present study, we
investigated the mechanism of the regulation of STING expression in relation to
the RIG-I pathway. Our data show that signaling through RIG-I induces STING
expression at both the transcriptional and protein levels in various cell types.
STING induction by the RIG-I agonist 5'triphosphorylated RNA (5'pppRNA) was
recognized to be a delayed event resulting from an autocrine/paracrine mechanism.
Indeed, cotreatment with tumor necrosis factor alpha and type I/II interferon was
found to have a synergistic effect on the regulation of STING expression and
could be potently decreased by impairing NF-kappaB and/or STAT1/2 signaling.
STING induction significantly contributed to sustainment of the immune signaling
cascade following 5'pppRNA treatment. Physiologically, this cross talk between
the RNA- and DNA-sensing pathways allowed 5'pppRNA to efficiently block infection
by herpes simplex virus 1 (HSV-1) both in vitro and in vivo in a STING-dependent
fashion. These observations demonstrate that STING induction by RIG-I signaling
through the NF-kappaB and STAT1/2 cascades is essential for RIG-I agonist
mediated HSV-1 restriction. IMPORTANCE: The innate immune system represents the
first line of defense against invading pathogens. The dysregulation of this
system can result in failure to combat pathogens, inflammation, and autoimmune
diseases. Thus, precise regulation at each level of the innate immune system is
crucial. Recently, a number of studies have established STING to be a central
molecule in the innate immune response to cytosolic DNA and RNA derived from
pathogens. Here, we describe the regulation of STING via RIG-I-mediated innate
immune sensing. We found that STING is synergistically induced via
proinflammatory and antiviral cytokine cascades. In addition, we show that in
vivo protection against herpes simplex virus 1 (HSV-1) by a RIG-I agonist
required STING. Our study provides new insights into the cross talk between DNA
and RNA pathogen-sensing systems via the control of STING.
PMID- 27512061
TI - In Vivo Conditions Enable IFNAR-Independent Type I Interferon Production by
Peritoneal CD11b+ Cells upon Thogoto Virus Infection.
AB - Type I interferons (IFNs) crucially contribute to host survival upon viral
infections. Robust expression of type I IFNs (IFN-alpha/beta) and induction of an
antiviral state critically depend on amplification of the IFN signal via the type
I IFN receptor (IFNAR). A small amount of type I IFN produced early upon virus
infection binds the IFNAR and activates a self-enhancing positive feedback loop,
resulting in induction of large, protective amounts of IFN-alpha. Unexpectedly,
we found robust, systemic IFN-alpha expression upon infection of IFNAR knockout
mice with the orthomyxovirus Thogoto virus (THOV). The IFNAR-independent IFN
alpha production required in vivo conditions and was not achieved during in vitro
infection. Using replication-incompetent THOV-derived virus-like particles, we
demonstrate that IFNAR-independent type I IFN induction depends on viral
polymerase activity but is largely independent of viral replication. To discover
the cell type responsible for this effect, we used type I IFN reporter mice and
identified CD11b(+) F4/80(+) myeloid cells within the peritoneal cavity of
infected animals as the main source of IFNAR-independent type I IFN,
corresponding to the particular tropism of THOV for this cell type. IMPORTANCE:
Type I IFNs are crucial for the survival of a host upon most viral infections,
and, moreover, they shape subsequent adaptive immune responses. Production of
protective amounts of type I IFN critically depends on the positive feedback
amplification via the IFNAR. Unexpectedly, we observed robust IFNAR-independent
type I IFN expression upon THOV infection and unraveled molecular mechanisms and
determined the tissue and cell type involved. Our data indicate that the host can
effectively use alternative pathways to induce type I IFN responses if the
classical feedback amplification is not available. Understanding how type I IFN
can be produced in large amounts independently of IFNAR-dependent enhancement
will identify mechanisms which might contribute to novel therapeutic strategies
to fight viral pathogens.
PMID- 27512062
TI - NF-kappaB and IRF1 Induce Endogenous Retrovirus K Expression via Interferon
Stimulated Response Elements in Its 5' Long Terminal Repeat.
AB - Thousands of endogenous retroviruses (ERV), viral fossils of ancient germ line
infections, reside within the human genome. Evidence of ERV activity has been
observed widely in both health and disease. While this is most often cited as a
bystander effect of cell culture or disease states, it is unclear which signals
control ERV transcription. Bioinformatic analysis suggests that the viral
promoter of endogenous retrovirus K (ERVK) is responsive to inflammatory
transcription factors. Here we show that one reason for ERVK upregulation in
amyotrophic lateral sclerosis (ALS) is the presence of functional interferon
stimulated response elements (ISREs) in the viral promoter. Transcription factor
overexpression assays revealed independent and synergistic upregulation of ERVK
by interferon regulatory factor 1 (IRF1) and NF-kappaB isoforms. Tumor necrosis
factor alpha (TNF-alpha) and LIGHT cytokine treatments of human astrocytes and
neurons enhanced ERVK transcription and protein levels through IRF1 and NF-kappaB
binding to the ISREs. We further show that in ALS brain tissue, neuronal ERVK
reactivation is associated with the nuclear translocation of IRF1 and NF-kappaB
isoforms p50 and p65. ERVK overexpression can cause motor neuron pathology in
murine models. Our results implicate neuroinflammation as a key trigger of ERVK
provirus reactivation in ALS. These molecular mechanisms may also extend to the
pathobiology of other ERVK-associated inflammatory diseases, such as cancers, HIV
infection, rheumatoid arthritis, and schizophrenia. IMPORTANCE: It has been well
established that inflammatory signaling pathways in ALS converge at NF-kappaB to
promote neuronal damage. Our findings suggest that inflammation-driven IRF1 and
NF-kappaB activity promotes ERVK reactivation in neurons of the motor cortex in
ALS. Thus, quenching ERVK activity through antiretroviral or immunomodulatory
regimens may hinder virus-mediated neuropathology and improve the symptoms of ALS
or other ERVK-associated diseases.
PMID- 27512063
TI - B Virus (Macacine Herpesvirus 1) Divergence: Variations in Glycoprotein D from
Clinical and Laboratory Isolates Diversify Virus Entry Strategies.
AB - B virus (Macacine herpesvirus 1) can cause deadly zoonotic disease in humans.
Molecular mechanisms of B virus cell entry are poorly understood for both
macaques and humans. Here we investigated the abilities of clinical B virus
isolates to use entry receptors of herpes simplex viruses (HSV). We showed that
resistant B78H1 cells became susceptible to B virus clinical strains upon
expression of either human nectin-2 or nectin-1. Antibody against glycoprotein D
(gD) protected these nectin-bearing cells from B virus infection, and a gD
negative recombinant B virus failed to enter these cells, indicating that the
nectin-mediated B virus entry depends on gD. We observed that the infectivity of
B virus isolates with a single amino acid substitution (D122N) in the IgV-core of
the gD ectodomain was impaired on nectin-1-bearing cells. Computational homology
based modeling of the B virus gD-nectin-1 complex revealed conformational
differences between the structures of the gD-122N and gD-122D variants that
affected the gD-nectin-1 protein-protein interface and binding affinity. Unlike
HSV, B virus clinical strains were unable to use herpesvirus entry mediator
(HVEM) as a receptor, regardless of conservation of the gD amino acid residues
essential for HSV-1 entry via HVEM. Based on the model of the B virus gD-HVEM
interface, we predict that residues R7, R11, and G15 are largely responsible for
the inability of B virus to utilize HVEM for entry. The ability of B virus to
enter cells of a human host by using a combination of receptors distinct from
those for HSV-1 or HSV-2 suggests a possible mechanism of enhanced
neuropathogenicity associated with zoonotic infections. IMPORTANCE: B virus
causes brainstem destruction in infected humans in the absence of timely
diagnosis and intervention. Nectins are cell adhesion molecules that are widely
expressed in human tissues, including neurons and neuronal synapses. Here we
report that human nectin-2 is a target receptor for B virus entry, in addition to
the reported receptor human nectin-1. Similar to a B virus lab strain, B virus
clinical strains can effectively use both nectin-1 and nectin-2 as cellular
receptors for entry into human cells, but unlike HSV-1 and HSV-2, none of the
clinical strains uses an HVEM-mediated entry pathway. Ultimately, these
differences between B virus and HSV-1 and -2 may provide insight into the
neuropathogenicity of B virus during zoonotic infections.
PMID- 27512064
TI - Epitope-Independent Purification of Native-Like Envelope Trimers from Diverse HIV
1 Isolates.
AB - Soluble forms of trimeric HIV-1 envelope glycoprotein (Env) have long been sought
as immunogens and as reagents for analysis of Env structure and function.
Isolation of trimers that mimic native Env, derived from diverse viruses,
however, represents a major challenge. Thus far, the most promising native-like
(NL) structures have been obtained by engineering trimer-stabilizing mutations,
termed SOSIP, into truncated Env sequences. However, the abundances of NL
trimeric conformers vary among Envs, necessitating purification by monoclonal
antibodies (MAbs) like PGT145, which target specific epitopes. To surmount this
inherent limitation, we developed an approach that uses lectin affinity
chromatography, ion-exchange chromatography, hydrophobic-interaction
chromatography (HIC), and size exclusion chromatography (SEC) to isolate NL
trimers from nonnative Env species. We validated this method with SOSIP trimers
from HIV-1 clades A and B. Analyses by SEC, blue native PAGE, SDS-PAGE, and
dynamic light scattering indicated that the resulting material was homogeneous
(>95% pure), fully cleaved, and of the appropriate molecular weight and size for
SOSIP trimers. Negative-stain electron microscopy further demonstrated that our
preparations were composed of NL trimeric structures. By hydrogen/deuterium
exchange mass spectrometry, these HIC-pure trimers exhibited structural
organization consistent with NL trimers and inconsistent with profiles seen in
nonnative Envs. Screened for antigenicity, some Envs, like BS208.b1 and KNH1144
T162A, did not present the glycan/quaternary structure-dependent epitope for
PGT145 binding, suggesting that these SOSIPs would be challenging to isolate by
existing MAb affinity methods. By selecting based on biochemical rather than
antigenic properties, our method offers an epitope-independent alternative to
MAbs for isolation of NL Env trimers. IMPORTANCE: The production and purification
of diverse soluble Env trimers that maintain native-like (NL) structure present
technical challenges that must be overcome in order to advance vaccine
development and provide reagents for HIV research. Low levels of NL trimer
expression amid heterogeneous Env conformers, even with the addition of
stabilizing mutations, have presented a major challenge. In addition, it has been
difficult to separate the NL trimers from these heterogeneous mixtures. While
MAbs with specificity for quaternary NL trimer epitopes have provided one
approach to purifying the desirable species, such methods are dependent on the
Env displaying the proper epitope. In addition, MAb affinity chromatography can
be expensive, the necessary MAb may be in limited supply, and large-scale
purification may not be feasible. Our method based on biochemical separation
techniques offers an epitope-independent approach to purification of NL trimers
with general application to diverse Envs.
PMID- 27512065
TI - Avian Leukosis Virus Activation of an Antisense RNA Upstream of TERT in B-Cell
Lymphomas.
AB - Avian leukosis virus (ALV) induces tumors by integrating its proviral DNA into
the chicken genome and altering the expression of nearby genes via strong
promoter and enhancer elements. Viral integration sites that contribute to
oncogenesis are selected in tumor cells. Deep-sequencing analysis of B-cell
lymphoma DNA confirmed that the telomerase reverse transcriptase (TERT) gene
promoter is a common ALV integration target. Twenty-six unique proviral
integration sites were mapped between 46 and 3,552 nucleotides (nt) upstream of
the TERT transcription start site, predominantly in the opposite transcriptional
orientation to TERT Transcriptome-sequencing (RNA-seq) analysis of normal bursa
revealed a transcribed region upstream of TERT in the opposite orientation,
suggesting the TERT promoter is bidirectional. This transcript appears to be an
uncharacterized antisense RNA. We have previously shown that TERT expression is
upregulated in tumors with integrations in the TERT promoter region. We now
report that the viral promoter drives the expression of a chimeric transcript
containing viral sequences spliced to exons 4 through 7 of this antisense RNA.
Clonal expansion of cells with ALV integrations driving overexpression of the
TERT antisense RNA suggest it may have a role in tumorigenesis. IMPORTANCE: The
data suggest that ALV integrations in the TERT promoter region drive the
overexpression of a novel antisense RNA and contribute to the development of
lymphomas.
PMID- 27512066
TI - Inhibition of the Membrane Attack Complex by Dengue Virus NS1 through Interaction
with Vitronectin and Terminal Complement Proteins.
AB - : Dengue virus (DENV) infects millions of people worldwide and is a major public
health problem. DENV nonstructural protein 1 (NS1) is a conserved glycoprotein
that associates with membranes and is also secreted into the plasma in DENV
infected patients. The present study describes a novel mechanism by which NS1
inhibits the terminal complement pathway. We first identified the terminal
complement regulator vitronectin (VN) as a novel DENV2 NS1 binding partner by
using a yeast two-hybrid system. This interaction was further assessed by enzyme
linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) assay. The
NS1-VN complex was also detected in plasmas from DENV-infected patients,
suggesting that this interaction occurs during DENV infection. We also
demonstrated that the DENV2 NS1 protein, either by itself or by interacting with
VN, hinders the formation of the membrane attack complex (MAC) and C9
polymerization. Finally, we showed that DENV2, West Nile virus (WNV), and Zika
virus (ZIKV) NS1 proteins produced in mammalian cells inhibited C9
polymerization. Taken together, our results points to a role for NS1 as a
terminal pathway inhibitor of the complement system. IMPORTANCE: Dengue is the
most important arthropod-borne viral disease nowadays and is caused by dengue
virus (DENV). The flavivirus NS1 glycoprotein has been characterized functionally
as a complement evasion protein that can attenuate the activation of the
classical, lectin, and alternative pathways. The present study describes a novel
mechanism by which DENV NS1 inhibits the terminal complement pathway. We
identified the terminal complement regulator vitronectin (VN) as a novel DENV NS1
binding partner, and the NS1-VN complex was detected in plasmas from DENV
infected patients, suggesting that this interaction occurs during DENV infection.
We also demonstrated that the NS1-VN complex inhibited membrane attack complex
(MAC) formation, thus interfering with the complement terminal pathway.
Interestingly, NS1 itself also inhibited MAC activity, suggesting a direct role
of this protein in the inhibition process. Our findings imply a role for NS1 as a
terminal pathway inhibitor of the complement system.
PMID- 27512067
TI - Activation of the Chicken Anemia Virus Apoptin Protein by Chk1/2 Phosphorylation
Is Required for Apoptotic Activity and Efficient Viral Replication.
AB - Chicken anemia virus (CAV) is a single-stranded circular DNA virus that carries 3
genes, the most studied of which is the gene encoding VP3, also known as apoptin.
This protein has been demonstrated to specifically kill transformed cells while
leaving normal cells unharmed in a manner that is independent of p53 status.
Although the mechanistic basis for this differential activity is unclear, it is
evident that the subcellular localization of the protein is important for the
difference. In normal cells, apoptin exists in filamentous networks in the
cytoplasm, whereas in transformed cells, apoptin is present in the nucleus and
appears as distinct foci. We have previously demonstrated that DNA damage
signaling through the ataxia telangiectasia mutated (ATM) pathway induces the
translocation of apoptin from the cytoplasm to the nucleus, where it induces
apoptosis. We found that apoptin contains four checkpoint kinase consensus sites
and that mutation of either threonine 56 or 61 to alanine restricts apoptin to
the cytoplasm. Furthermore, treatment of tumor cells expressing apoptin with
inhibitors of checkpoint kinase 1 (Chk1) and Chk2 causes apoptin to localize to
the cytoplasm. Importantly, silencing of Chk2 rescues cancer cells from the
cytotoxic effects of apoptin. Finally, treatment of virus-producing cells with
Chk inhibitor protects them from virus-mediated toxicity and reduces the titer of
progeny virus. Taken together, our results indicate that apoptin is a sensor of
DNA damage signaling through the ATM-Chk2 pathway, which induces it to migrate to
the nucleus during viral replication. IMPORTANCE: The chicken anemia virus (CAV)
protein apoptin is known to induce tumor cell-specific death when expressed.
Therefore, understanding its regulation and mechanism of action could provide new
insights into tumor cell biology. We have determined that checkpoint kinase 1 and
2 signaling is important for apoptin regulation and is a likely feature of both
tumor cells and host cells producing virus progeny. Inhibition of checkpoint
signaling prevents apoptin toxicity in tumor cells and attenuates CAV
replication, suggesting it may be a future target for antiviral therapy.
PMID- 27512068
TI - Human IFIT1 Inhibits mRNA Translation of Rubulaviruses but Not Other Members of
the Paramyxoviridae Family.
AB - We have previously shown that IFIT1 is primarily responsible for the antiviral
action of interferon (IFN) alpha/beta against parainfluenza virus type 5 (PIV5),
selectively inhibiting the translation of PIV5 mRNAs. Here we report that while
PIV2, PIV5, and mumps virus (MuV) are sensitive to IFIT1, nonrubulavirus members
of the paramyxoviridae such as PIV3, Sendai virus (SeV), and canine distemper
virus (CDV) are resistant. The IFIT1 sensitivity of PIV5 was not rescued by
coinfection with an IFIT1-resistant virus (PIV3), demonstrating that PIV3 does
not specifically inhibit the antiviral activity of IFIT1 and that the inhibition
of PIV5 mRNAs is regulated by cis-acting elements. We developed an in vitro
translation system using purified human IFIT1 to further investigate the
mechanism of action of IFIT1. While the translations of PIV2, PIV5, and MuV mRNAs
were directly inhibited by IFIT1, the translations of PIV3, SeV, and CDV mRNAs
were not. Using purified human mRNA-capping enzymes, we show biochemically that
efficient inhibition by IFIT1 is dependent upon a 5' guanosine nucleoside cap
(which need not be N7 methylated) and that this sensitivity is partly abrogated
by 2'O methylation of the cap 1 ribose. Intriguingly, PIV5 M mRNA, in contrast to
NP mRNA, remained sensitive to inhibition by IFIT1 following in vitro 2'O
methylation, suggesting that other structural features of mRNAs may influence
their sensitivity to IFIT1. Thus, surprisingly, the viral polymerases (which have
2'-O-methyltransferase activity) of rubulaviruses do not protect these viruses
from inhibition by IFIT1. Possible biological consequences of this are discussed.
IMPORTANCE: Paramyxoviruses cause a wide variety of diseases, and yet most of
their genes encode structural proteins and proteins involved in their replication
cycle. Thus, the amount of genetic information that determines the type of
disease that paramyxoviruses cause is relatively small. One factor that will
influence disease outcomes is how they interact with innate host cell defenses,
including the interferon (IFN) system. Here we show that different
paramyxoviruses interact in distinct ways with cells in a preexisting IFN-induced
antiviral state. Strikingly, all the rubulaviruses tested were sensitive to the
antiviral action of ISG56/IFIT1, while all the other paramyxoviruses tested were
resistant. We developed novel in vitro biochemical assays to investigate the
mechanism of action of IFIT1, demonstrating that the mRNAs of rubulaviruses can
be directly inhibited by IFIT1 and that this is at least partially because their
mRNAs are not correctly methylated.
PMID- 27512069
TI - Long and Short Isoforms of the Human Cytomegalovirus UL138 Protein Silence IE
Transcription and Promote Latency.
AB - The UL133-138 locus present in clinical strains of human cytomegalovirus (HCMV)
encodes proteins required for latency and reactivation in CD34(+) hematopoietic
progenitor cells and virion maturation in endothelial cells. The encoded proteins
form multiple homo- and hetero-interactions and localize within secretory
membranes. One of these genes, UL136 gene, is expressed as at least five
different protein isoforms with overlapping and unique functions. Here we show
that another gene from this locus, the UL138 gene, also generates more than one
protein isoform. A long form of UL138 (pUL138-L) initiates translation from codon
1, possesses an amino-terminal signal sequence, and is a type one integral
membrane protein. Here we identify a short protein isoform (pUL138-S) initiating
from codon 16 that displays a subcellular localization similar to that of pUL138
L. Reporter, short-term transcription, and long-term virus production assays
revealed that both pUL138-L and pUL138-S are able to suppress major immediate
early (IE) gene transcription and the generation of infectious virions in cells
in which HCMV latency is studied. The long form appears to be more potent at
silencing IE transcription shortly after infection, while the short form seems
more potent at restricting progeny virion production at later times, indicating
that both isoforms of UL138 likely cooperate to promote HCMV latency. IMPORTANCE:
Latency allows herpesviruses to persist for the lives of their hosts in the face
of effective immune control measures for productively infected cells. Controlling
latent reservoirs is an attractive antiviral approach complicated by knowledge
deficits for how latently infected cells are established, maintained, and
reactivated. This is especially true for betaherpesviruses. The functional
consequences of HCMV UL138 protein expression during latency include repression
of viral IE1 transcription and suppression of virus replication. Here we show
that short and long isoforms of UL138 exist and can themselves support latency
but may do so in temporally distinct manners. Understanding the complexity of
gene expression and its impact on latency is important for considering potential
antivirals targeting latent reservoirs.
PMID- 27512071
TI - In Vitro Studies Show that Sequence Variability Contributes to Marked Variation
in Hepatitis B Virus Replication, Protein Expression, and Function Observed
across Genotypes.
AB - : The hepatitis B virus (HBV) exists as 9 major genotypes (A to I), one minor
strain (designated J) and multiple subtypes. Marked differences in HBV natural
history, disease progression and treatment response are exhibited by many of
these genotypes and subtypes. For example, HBV genotype C is associated with
later hepatitis B e antigen (HBeAg) seroconversion and high rates of liver cancer
compared to other HBV genotypes, whereas genotype A2 is rarely associated with
HBeAg-negative disease or liver cancer. The reasons for these and other
differences in HBV natural history are yet to be determined but could in part be
due to sequence differences in the HBV genome that alter replicative capacity
and/or gene expression. Direct comparative studies on HBV replication and protein
expression have been limited to date due largely to the absence of infectious HBV
cDNA clones for each of the HBV genotypes present in the same genetic
arrangement. We have produced replication-competent infectious cDNA clones of the
most common subtypes of genotypes A to D, namely, A2, B2, C2, D3, and the minor
strain J, and compared their HBV replication phenotype using transient
transfection models. We identified striking differences in HBV replicative
capacity as well as HBeAg and surface (HBsAg) protein expression across
genotypes, which may in part be due to sequence variability in regulatory regions
of the HBV genome. Functional analysis showed that sequence differences in the
major upstream regulatory region across genotypes impacted promoter activity.
IMPORTANCE: There have been very few studies directly comparing the replication
phenotype of different HBV genotypes, for which there are marked differences in
natural history and disease progression worldwide. We have generated replication
competent 1.3-mer cDNA clones of the major genotypes A2, B2, C2, and D3, as well
as a recently identified strain J, and identified striking differences in
replicative capacity and protein expression that may contribute to some of the
observed differences in HBV natural history observed globally.
PMID- 27512070
TI - Heat Shock Protein 70 Family Members Interact with Crimean-Congo Hemorrhagic
Fever Virus and Hazara Virus Nucleocapsid Proteins and Perform a Functional Role
in the Nairovirus Replication Cycle.
AB - The Nairovirus genus of the Bunyaviridae family contains serious human and animal
pathogens classified within multiple serogroups and species. Of these serogroups,
the Crimean-Congo hemorrhagic fever virus (CCHFV) serogroup comprises sole
members CCHFV and Hazara virus (HAZV). CCHFV is an emerging zoonotic virus that
causes often-fatal hemorrhagic fever in infected humans for which preventative or
therapeutic strategies are not available. In contrast, HAZV is nonpathogenic to
humans and thus represents an excellent model to study aspects of CCHFV biology
under conditions of more-accessible biological containment. The three RNA
segments that form the nairovirus genome are encapsidated by the viral
nucleocapsid protein (N) to form ribonucleoprotein (RNP) complexes that are
substrates for RNA synthesis and packaging into virus particles. We used
quantitative proteomics to identify cellular interaction partners of CCHFV N and
identified robust interactions with cellular chaperones. These interactions were
validated using immunological methods, and the specific interaction between
native CCHFV N and cellular chaperones of the HSP70 family was confirmed during
live CCHFV infection. Using infectious HAZV, we showed for the first time that
the nairovirus N-HSP70 association was maintained within both infected cells and
virus particles, where N is assembled as RNPs. Reduction of active HSP70 levels
in cells by the use of small-molecule inhibitors significantly reduced HAZV
titers, and a model for chaperone function in the context of high genetic
variability is proposed. These results suggest that chaperones of the HSP70
family are required for nairovirus replication and thus represent a genetically
stable cellular therapeutic target for preventing nairovirus-mediated disease.
IMPORTANCE: Nairoviruses compose a group of human and animal viruses that are
transmitted by ticks and associated with serious or fatal disease. One member is
Crimean-Congo hemorrhagic fever virus (CCHFV), which is responsible for fatal
human disease and is recognized as an emerging threat within Europe in response
to climate change. No preventative or therapeutic strategies against nairovirus
mediated disease are currently available. Here we show that the N protein of
CCHFV and the related Hazara virus interact with a cellular protein, HSP70,
during both the intracellular and extracellular stages of the virus life cycle.
The use of inhibitors that block HSP70 function reduces virus titers by up to
1,000-fold, suggesting that this interaction is important within the context of
the nairovirus life cycle and may represent a potent target for antinairovirus
therapies against which the virus cannot easily develop resistance.
PMID- 27512072
TI - Interrelationship of Primary Virus Replication, Level of Latency, and Time to
Reactivation in the Trigeminal Ganglia of Latently Infected Mice.
AB - We sought to determine the possibility of an interrelationship between primary
virus replication in the eye, the level of viral DNA in the trigeminal ganglia
(TG) during latency, and the amount of virus reactivation following ocular herpes
simplex virus type 1 (HSV-1) infection. Mice were infected with virulent (McKrae)
or avirulent (KOS and RE) strains of HSV-1, and virus titers in the eyes and TG
during primary infection, level of viral gB DNA in TG on day 28 postinfection
(p.i.), and virus reactivation on day 28 p.i. as measured by explant reactivation
were calculated. Our results suggest that the avirulent strains of HSV-1, even
after corneal scarification, had lower virus titers in the eye, had less latency
in the TG, and took a longer time to reactivate than virulent strains of HSV-1.
The time to explant reactivation of avirulent strains of HSV-1 was similar to
that of the virulent LAT((-)) McKrae-derived mutant. The viral dose with the
McKrae strain of HSV-1 affected the level of viral DNA and time to explant
reactivation. Overall, our results suggest that there is no absolute correlation
between primary virus titer in the eye and TG and the level of viral DNA in
latent TG and time to reactivation. IMPORTANCE: Very little is known regarding
the interrelationship between primary virus replication in the eye, the level of
latency in TG, and the time to reactivate in the mouse model. This study was
designed to answer these questions. Our results point to the absence of any
correlation between the level of primary virus replication and the level of viral
DNA during latency, and neither was an indicator of how rapidly the virus
reactivated following explant TG-induced reactivation.
PMID- 27512073
TI - Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in
Epidemic Keratoconjunctivitis.
AB - : Human adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each
associated with specific disease conditions. Among these, HAdV-D includes those
viruses associated with epidemic keratoconjunctivitis (EKC), a severe ocular
surface infection. The reasons for corneal tropism for some but not all HAdV-Ds
are not known. The fiber protein is a major capsid protein; its C-terminal "knob"
mediates binding with host cell receptors to facilitate subsequent viral entry.
In a comprehensive phylogenetic analysis of HAdV-D capsid genes, fiber knob gene
sequences of HAdV-D types associated with EKC formed a unique clade. By
proteotyping analysis, EKC virus-associated fiber knobs were uniquely shared.
Comparative structural modeling showed no distinct variations in fiber knobs of
EKC types but did show variation among HAdV-Ds in a region overlapping with the
known CD46 binding site in HAdV-B. We also found signature amino acid positions
that distinguish EKC from non-EKC types, and by in vitro studies we showed that
corneal epithelial cell tropism can be predicted by the presence of a lysine or
alanine at residue 240. This same amino acid residue in EKC viruses shows
evidence for positive selection, suggesting that evolutionary pressure enhances
fitness in corneal infection, and may be a molecular determinant in EKC
pathogenesis. IMPORTANCE: Viruses adapt various survival strategies to gain entry
into target host cells. Human adenovirus (HAdV) types are associated with
distinct disease conditions, yet evidence for connections between genotype and
cellular tropism is generally lacking. Here, we provide a structural and
evolutionary basis for the association between specific genotypes within HAdV
species D and epidemic keratoconjunctivitis, a severe ocular surface infection.
We find that HAdV-D fiber genes of major EKC pathogens, specifically the fiber
knob gene region, share a distinct phylogenetic clade. Deeper analysis of the
fiber gene revealed that evolutionary pressure at crucial amino acid sites has a
significant impact on its structural conformation, which is likely important in
host cell binding and entry. Specific amino acids in hot spot residues provide a
link to ocular cell tropism and possibly to corneal pathogenesis.
PMID- 27512074
TI - Novel Acylguanidine-Based Inhibitor of HIV-1.
AB - The emergence of transmissible HIV-1 strains with resistance to antiretroviral
drugs highlights a continual need for new therapies. Here we describe a novel
acylguanidine-containing compound, 1-(2-(azepan-1-yl)nicotinoyl)guanidine (or
SM111), that inhibits in vitro replication of HIV-1, including strains resistant
to licensed protease, reverse transcriptase, and integrase inhibitors, without
major cellular toxicity. At inhibitory concentrations, intracellular p24(Gag)
production was unaffected, but virion release (measured as extracellular
p24(Gag)) was reduced and virion infectivity was substantially impaired,
suggesting that SM111 acts at a late stage of viral replication. SM111-mediated
inhibition of HIV-1 was partially overcome by a Vpu I17R mutation alone or a Vpu
W22* truncation in combination with Env N136Y. These mutations enhanced virion
infectivity and Env expression on the surface of infected cells in the absence
and presence of SM111 but also impaired Vpu's ability to downregulate CD4 and
BST2/tetherin. Taken together, our results support acylguanidines as a class of
HIV-1 inhibitors with a distinct mechanism of action compared to that of licensed
antiretrovirals. Further research on SM111 and similar compounds may help to
elucidate knowledge gaps related to Vpu's role in promoting viral egress and
infectivity. IMPORTANCE: New inhibitors of HIV-1 replication may be useful as
therapeutics to counteract drug resistance and as reagents to perform more
detailed studies of viral pathogenesis. SM111 is a small molecule that blocks the
replication of wild-type and drug-resistant HIV-1 strains by impairing viral
release and substantially reducing virion infectivity, most likely through its
ability to prevent Env expression at the infected cell surface. Partial
resistance to SM111 is mediated by mutations in Vpu and/or Env, suggesting that
the compound affects host/viral protein interactions that are important during
viral egress. Further characterization of SM111 and similar compounds may allow
more detailed pharmacological studies of HIV-1 egress and provide opportunities
to develop new treatments for HIV-1.
PMID- 27512075
TI - Identification of Residues That Affect Oligomerization and/or Enzymatic Activity
of Influenza Virus H5N1 Neuraminidase Proteins.
AB - Influenza A virus (IAV) attachment to and release from sialoside receptors is
determined by the balance between hemagglutinin (HA) and neuraminidase (NA). The
molecular determinants that mediate the specificity and activity of NA are still
poorly understood. In this study, we aimed to design the optimal recombinant
soluble NA protein to identify residues that affect NA enzymatic activity. To
this end, recombinant soluble versions of four different NA proteins from H5N1
viruses were compared with their full-length counterparts. The soluble NA
ectodomains were fused to three commonly used tetramerization domains. Our
results indicate that the particular oligomerization domain used does not affect
the Km value but may affect the specific enzymatic activity. This particularly
holds true when the stalk domain is included and for NA ectodomains that display
a low intrinsic ability to oligomerize. NA ectodomains extended with a
Tetrabrachion domain, which forms a nearly parallel four-helix bundle, better
mimicked the enzymatic properties of full-length proteins than when other coiled
coil tetramerization domains were used, which probably distort the stalk domain.
Comparison of different NA proteins and mutagenic analysis of recombinant soluble
versions thereof resulted in the identification of several residues that affected
oligomerization of the NA head domain (position 95) and therefore the specific
activity or sialic acid binding affinity (Km value; positions 252 and 347). This
study demonstrates the potential of using recombinant soluble NA proteins to
reveal determinants of NA assembly and enzymatic activity. IMPORTANCE: The IAV HA
and NA glycoproteins are important determinants of host tropism and
pathogenicity. However, NA is relatively understudied compared to HA. Analysis of
soluble versions of these glycoproteins is an attractive way to study their
activities, as they are easily purified from cell culture media and applied in
downstream assays. In the present study, we analyzed the enzymatic activity of
different NA ectodomains with three commonly used tetramerization domains and
compared them with full-length NA proteins. By performing a mutagenic analysis,
we identified several residues that affected NA assembly, activity, and/or
substrate binding. In addition, our results indicate that the design of the
recombinant soluble NA protein, including the particular tetramerization domain,
is an important determinant for maintaining the enzymatic properties within the
head domain. NA ectodomains extended with a Tetrabrachion domain better mimicked
the full-length proteins than when the other tetramerization domains were used.
PMID- 27512076
TI - Effects of Membrane Charge and Order on Membrane Binding of the Retroviral
Structural Protein Gag.
AB - The retroviral structural protein Gag binds to the inner leaflet of the plasma
membrane (PM), and many cellular proteins do so as well. We used Rous sarcoma
virus (RSV) Gag together with membrane sensors to study the principles governing
peripheral protein membrane binding, including electrostatics, specific
recognition of phospholipid headgroups, sensitivity to phospholipid acyl chain
compositions, preference for membrane order, and protein multimerization. We used
an in vitro liposome-pelleting assay to test protein membrane binding properties
of Gag, the well-characterized MARCKS peptide, a series of fluorescent
electrostatic sensor proteins (mNG-KRn), and the specific phosphatidylserine (PS)
binding protein Evectin2. RSV Gag and mNG-KRn bound well to membranes with
saturated and unsaturated acyl chains, whereas the MARCKS peptide and Evectin2
preferentially bound to membranes with unsaturated acyl chains. To further
discriminate whether the primary driving force for Gag membrane binding is
electrostatic interactions or preference for membrane order, we measured protein
binding to giant unilamellar vesicles (GUVs) containing the same PS concentration
in both disordered (Ld) and ordered (Lo) phases. RSV Gag and mNG-KRn membrane
association followed membrane charge, independent of membrane order. Consistent
with pelleting data, the MARCKS peptide showed preference for the Ld domain.
Surprisingly, the PS sensor Evectin2 bound to the PS-rich Ld domain with 10-fold
greater affinity than to the PS-rich Lo domain. In summary, we found that RSV Gag
shows no preference for membrane order, while proteins with reported membrane
penetrating domains show preference for disordered membranes. IMPORTANCE:
Retroviral particles assemble on the PM and bud from infected cells. Our
understanding of how Gag interacts with the PM and how different membrane
properties contribute to overall Gag assembly is incomplete. This study examined
how membrane charge and membrane order influence Gag membrane association.
Consistent with previous work on RSV Gag, we report here that electrostatic
interactions provide the primary driving force for RSV Gag membrane association.
Using phase-separated GUVs with known lipid composition of the Ld and Lo phases,
we demonstrate for the first time that RSV Gag is sensitive to membrane charge
but not membrane order. In contrast, the cellular protein domain MARCKS and the
PS sensor Evectin2 show preference for disordered membranes. We also demonstrate
how to define GUV phase composition, which could serve as a tool in future
studies of protein membrane interactions.
PMID- 27512077
TI - ARID3B: a Novel Regulator of the Kaposi's Sarcoma-Associated Herpesvirus Lytic
Cycle.
AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of commonly
fatal malignancies of immunocompromised individuals, including primary effusion
lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is
their biphasic life cycle-viral latency and the productive lytic cycle-and it is
well established that reactivation of the KSHV lytic cycle is associated with KS
pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern
reactivation is required to better understand disease progression. The viral
protein replication and transcription activator (RTA) is the KSHV lytic switch
protein due to its ability to drive the expression of various lytic genes,
leading to reactivation of the entire lytic cycle. While the mechanisms for
activating lytic gene expression have received much attention, how RTA impacts
cellular function is less well understood. To address this, we developed a cell
line with doxycycline-inducible RTA expression and applied stable isotope
labeling of amino acids in cell culture (SILAC)-based quantitative proteomics.
Using this methodology, we have identified a novel cellular protein (AT-rich
interacting domain containing 3B [ARID3B]) whose expression was enhanced by RTA
and that relocalized to replication compartments upon lytic reactivation. We also
show that small interfering RNA (siRNA) knockdown or overexpression of ARID3B led
to an enhancement or inhibition of lytic reactivation, respectively. Furthermore,
DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B
specifically interacts with A/T-rich elements in the KSHV origin of lytic
replication (oriLyt), and this was dependent on lytic cycle reactivation.
Therefore, we have identified a novel cellular protein whose expression is
enhanced by KSHV RTA with the ability to inhibit KSHV reactivation. IMPORTANCE:
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of fatal
malignancies of immunocompromised individuals, including Kaposi's sarcoma (KS).
Herpesviruses are able to establish a latent infection, in which they escape
immune detection by restricting viral gene expression. Importantly, however,
reactivation of productive viral replication (the lytic cycle) is necessary for
the pathogenesis of KS. Therefore, it is important that we comprehensively
understand the mechanisms that govern lytic reactivation, to better understand
disease progression. In this study, we have identified a novel cellular protein
(AT-rich interacting domain protein 3B [ARID3B]) that we show is able to temper
lytic reactivation. We showed that the master lytic switch protein, RTA, enhanced
ARID3B levels, which then interacted with viral DNA in a lytic cycle-dependent
manner. Therefore, we have added a new factor to the list of cellular proteins
that regulate the KSHV lytic cycle, which has implications for our understanding
of KSHV biology.
PMID- 27512078
TI - Baculovirus FP25K Localization: Role of the Coiled-Coil Domain.
AB - : Two types of viruses are produced during the baculovirus life cycle: budded
virus (BV) and occlusion-derived virus (ODV). A particular baculovirus protein,
FP25K, is involved in the switch from BV to ODV production. Previously, FP25K
from the model alphabaculovirus Autographa californica multiple
nucleopolyhedrovirus (AcMNPV) was shown to traffic ODV envelope proteins.
However, FP25K localization and the domains involved are inconclusive. Here we
used a quantitative approach to study FP25K subcellular localization during
infection using an AcMNPV bacmid virus that produces a functional AcMNPV FP25K
green fluorescent protein (GFP) fusion protein. During cell infection, FP25K-GFP
localized primarily to the cytoplasm, particularly amorphous structures, with a
small fraction being localized in the nucleus. To investigate the sequences
involved in FP25K localization, an alignment of baculovirus FP25K sequences
revealed that the N-terminal putative coiled-coil domain is present in all
alphabaculoviruses but absent in betabaculoviruses. Structural prediction
indicated a strong relatedness of AcMNPV FP25K to long interspersed element 1
(LINE-1) open reading frame 1 protein (ORF1p), which contains an N-terminal
coiled-coil domain responsible for cytoplasmic retention. Point mutations and
deletions of this domain lead to a change in AcMNPV FP25K localization from
cytoplasmic to nuclear. The coiled-coil and C-terminal deletion viruses increased
BV production. Furthermore, a betabaculovirus FP25K protein lacking this N
terminal coiled-coil domain localized predominantly to the nucleus and exhibited
increased BV production. These data suggest that the acquisition of this N
terminal coiled-coil domain in FP25K is important for the evolution of
alphabaculoviruses. Moreover, with the divergence of preocclusion nuclear
membrane breakdown in betabaculoviruses and membrane integrity in
alphabaculoviruses, this domain represents an alphabaculovirus adaptation for
nuclear trafficking of occlusion-associated proteins. IMPORTANCE: Baculovirus
infection produces two forms of viruses: BV and ODV. Manufacturing of ODV
involves trafficking of envelope proteins to the inner nuclear membrane, mediated
partly through the FP25K protein. Since FP25K is present in alpha-, beta-, and
gammabaculoviruses, it is uncertain if this trafficking function is conserved. In
this study, we looked at alpha- and betabaculovirus FP25K trafficking by its
localization. Alphabaculovirus FP25K localized primarily to the cytoplasm,
whereas betabaculovirus FP25K localized to the nucleus. We found that an N
terminal coiled-coil domain present in all alphabaculovirus FP25K proteins, but
absent in betabaculovirus FP25K, was critical for alphabaculovirus FP25K
cytoplasmic localization. We believe that this represents an evolutionary process
that partly led to the gain of function of this N-terminal coiled-coil domain in
alphabaculovirus FP25K to aid in nuclear trafficking of occlusion-associated
proteins. Due to betabaculovirus breakdown of the nuclear membrane before
occlusion, this function is not needed, and the domain was lost or never
acquired.
PMID- 27512080
TI - Combination Use of Clopidogrel and Proton Pump Inhibitors Increases Major Adverse
Cardiovascular Events in Patients With Coronary Artery Disease: A Meta-Analysis.
AB - BACKGROUND: Published data indicated that combination use of clopidogrel and
proton pump inhibitors (PPIs) may increase the incidence of major adverse
cardiovascular events (MACEs). This has been a highly controversial topic for
years. DESIGN: The present study was performed to evaluate whether combination
therapy of clopidogrel and PPIs is associated with increased risk of MACEs than
with clopidogrel alone in patients with coronary artery disease. METHODS: A
systematic search of MEDLINE, EMBASE, and the Cochrane Library was conducted for
studies recording the occurrence of MACEs in patients with exposure to
concomitant use of clopidogrel and PPIs up to February 2015. Odds ratios (ORs)
were combined using a random-effects model. RESULTS: Patients receiving
combination therapy with PPIs and clopidogrel were at significantly increased
risk of MACEs (OR: 1.42; 95% confidence interval [CI]: 1.30-1.55). Adding a PPI
to clopidogrel treatment was associated with a higher rate of MACE occurrence in
rapid metabolizers (RMs, *1/*1) of CYP2C19 (OR: 1.42; 95% CI: 1.12-1.81), but
there was no obviously increased rate (OR: 1.43; 95% CI: 0.89-2.28) in decreased
metabolizers (with 1 or 2 loss-of-function allele). The increased risk of MACEs
was similar in 4 classes of PPIs (omeprazole, lansoprazole, esomeprazole, and
pantoprazole), but rabeprazole (OR: 1.03; 95% CI: 0.55-1.95) wasn't. CONCLUSION:
The combination use of clopidogrel and certain types of PPIs (omeprazole,
lansoprazole, esomeprazole, pantoprazole) increases the risk of MACE in patients
with coronary artery disease. Only in the RMs of CYP2C19, PPIs were associated
with significantly increased MACE in patients coadministered with clopidogrel.
PMID- 27512079
TI - Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies
Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in
Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling.
AB - Cardiomyocytes undergo growth and remodeling in response to specific pathological
or physiological conditions. In the former, myocardial growth is a risk factor
for cardiac failure and faster protein synthesis is a major factor driving
cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro
hypertrophic stimuli on the synthesis of specific proteins in ARVC and to
determine whether such effects are caused by alterations on mRNA abundance or the
translation of specific mRNAs. Cardiomyocytes have very low rates of protein
synthesis, posing a challenging problem in terms of studying changes in the
synthesis of specific proteins, which also applies to other nondividing primary
cells. To study the rates of accumulation of specific proteins in these cells, we
developed an optimized version of the Quantitative Noncanonical Amino acid
Tagging LC/MS proteomic method to label and selectively enrich newly synthesized
proteins in these primary cells while eliminating the suppressive effects of pre
existing and highly abundant nonisotope-tagged polypeptides. Our data revealed
that a classical pathologic (phenylephrine; PE) and the recently identified
insulin stimulus that also contributes to the development of pathological cardiac
hypertrophy (insulin), both increased the synthesis of proteins involved in, e.g.
glycolysis, the Krebs cycle and beta-oxidation, and sarcomeric components.
However, insulin increased synthesis of many metabolic enzymes to a greater
extent than PE. Using a novel validation method, we confirmed that synthesis of
selected candidates is indeed up-regulated by PE and insulin. Synthesis of all
proteins studied was up-regulated by signaling through mammalian target of
rapamycin complex 1 without changes in their mRNA levels, showing the key
importance of translational control in the rapid effects of hypertrophic stimuli.
Expression of PKM2 was up-regulated in rat hearts following TAC. This isoform
possesses specific regulatory properties, so this finding indicates it may be
involved in metabolic remodeling and also serve as a novel candidate biomarker.
Levels of translation factor eEF1 also increased during TAC, likely contributing
to faster cell mass accumulation. Interestingly those two candidates were not up
regulated in pregnancy or exercise induced CH, indicating PKM2 and eEF1 were
pathological CH specific markers. We anticipate that the methodologies described
here will be valuable for other researchers studying protein synthesis in primary
cells.
PMID- 27512081
TI - Cholesteryl Ester Transfer Protein Inhibitors: Trials and Tribulations.
AB - The cholesteryl ester transfer protein (CETP) is a plasma protein that plays an
important role in the transfer of lipids between plasma lipoproteins. The CETP
inhibitors have been widely studied as a pharmacologic therapy to target plasma
cholesterol in order to reduce the risk of atherosclerotic cardiovascular disease
. Using CETP inhibitors as cholesterol modifiers was based on the genetic
research that found correlations between CETP activity and cholesterol levels.
Although CETP inhibitors are successful at altering targeted cholesterol markers,
recent phase 3 outcome trials have shown limited benefit on cardiovascular
outcomes when combined with the current standard of care. We discuss the science
of CETP inhibition, compare the CETP inhibitors developed (torcetrapib,
evacetrapib, dalcetrapib, and anacetrapib), the findings from the CETP inhibitor
trials, and the future outlook for CETP inhibitors in cholesterol modification.
PMID- 27512082
TI - Early and long-term outcome of infants born extremely preterm.
AB - There is no question that birth at extremely low gestational ages presents a
significant threat to an infant's survival, health and development. Growing
evidence suggests that gestational age may be conceptualised as a continuum in
which births before 28 weeks of gestation (extremely preterm: EP) represent the
severe end of a spectrum of health and developmental adversity. Although
comprising just 1%-2% of all births, EP deliveries pose the greatest challenge to
neonatal medicine and to health, education and social services for the provision
of ongoing support for survivors with additional needs. Studying the outcomes of
these infants remains critical for evaluating and enhancing clinical care,
planning long-term support and for advancing our understanding of the life-course
consequences of immaturity at birth. Here we review literature relating to early
and long-term neurodevelopmental, cognitive, behavioural and educational outcomes
following EP birth focusing on key themes and considering implications for
intervention.
PMID- 27512083
TI - On-tissue Direct Monitoring of Global Hydrogen/Deuterium Exchange by MALDI Mass
Spectrometry: Tissue Deuterium Exchange Mass Spectrometry (TDXMS).
AB - Hydrogen/deuterium exchange mass spectrometric (H/DXMS) methods for protein
structural analysis are conventionally performed in solution. We present Tissue
Deuterium Exchange Mass Spectrometry (TDXMS), a method to directly monitor
deuterium uptake on tissue, as a means to better approximate the deuterium
exchange behavior of proteins in their native microenvironment. Using this
method, a difference in deuterium uptake behavior was observed when the same
proteins were monitored in solution and on tissue. The higher maximum deuterium
uptake at equilibrium for all proteins analyzed in solution suggests a more open
conformation in the absence of interacting partners normally observed on tissue.
We also demonstrate a difference in the deuterium uptake behavior of a few
proteins across different morphological regions of the same tissue section.
Modifications of the total number of hydrogens exchanged, as well as the kinetics
of exchange, were both observed. These results provide information on the
implication of protein interactions with partners as well as on the
conformational changes related to these interactions, and illustrate the
importance of examining protein deuterium exchange behavior in the presence of
its specific microenvironment directly at the level of tissues.
PMID- 27512084
TI - Living with asthma and chronic obstructive airways disease: Using technology to
support self-management - An overview.
AB - Long-term respiratory conditions such as asthma and chronic obstructive pulmonary
disease (COPD) are common, and cause high levels of morbidity and mortality.
Supporting self-management is advocated for both asthma and increasingly so for
COPD, and there is growing interest in the potential role of a range of new
technologies, such as smartphone apps, the web or telehealth to facilitate and
promote self-management in these conditions. Treatment goals for both asthma and
COPD include aiming to control symptoms, maintain activities, achieve the best
possible quality of life and minimize risks of exacerbation. To do this, health
professionals should be (a) helping patients to recognize deteriorating symptoms
and act appropriately; (b) promoting adherence to maintenance therapy; (c)
promoting a regular review where triggers can be established, and strategies for
managing such triggers discussed; and (d) promoting healthy lifestyles and
positive self-management of symptoms. In particular, low uptake of asthma action
plans is a modifiable contributor to morbidity and possibly also to mortality in
those with asthma and should be addressed as a priority. Using technology to
support self-management is an evolving strategy that shows promise. This review
provides an overview of self-management support and discusses how newer
technologies may help patients and health professionals to meet key treatment
goals.
PMID- 27512085
TI - Mother-Daughter-Granddaughter Double GuideLiner Technique for Delivering Stents
Past Multiple Extreme Angulations.
PMID- 27512086
TI - Of Stents and Scaffolds: Trial Data and the Real World.
PMID- 27512088
TI - Intraindividual Comparison of Everolimus-Eluting Bioresorbable Vascular Scaffolds
Versus Drug-Eluting Metallic Stents.
AB - BACKGROUND: The performance of everolimus-eluting bioresorbable vascular scaffold
(BVS) versus drug-eluting metallic stent (DES) in the same individual receiving
multilesion percutaneous coronary intervention (PCI) remains poorly studied. This
report investigates the intraindividual performance of BVS and DES in patients
receiving multilesion PCI and follow-up angiography. METHODS AND RESULTS: Data of
patients undergoing BVS implantation for de novo lesions from 2012 to 2014 at 2
centers in Munich, Germany, were prospectively collected. Individuals receiving
multilesion PCI with BVS and DES and follow-up angiography at 6 to 8 months were
studied. Primary end point was in-device late lumen loss. Secondary end points
were binary restenosis, target lesion revascularization, and definite
stent/scaffold thrombosis. A total of 90 PCI patients with 239 lesions received
BVS (n=112) and DES (n=127). Follow-up angiography after a median of 6.6 months
(5.8-7.1) showed a higher degree of late lumen loss in lesions treated with BVS
versus DES (0.30+/-0.59 versus 0.22+/-0.48 mm; P=0.035). However, the adjustment
for baseline angiographic imbalances discarded an influence of stent type on late
lumen loss (P=0.82). At the same time point, binary restenosis was comparable
between BVS and DES (7.8% versus 8.9%; P=0.90). After a median of 13.2 months
(9.2-17.6), target lesion revascularization (9.8% versus 10.2%; P=0.97) and
definite stent/scaffold thrombosis (2.7% versus 1.6%; P=0.48) did not differ
between BVS and DES. CONCLUSIONS: In patients receiving multilesion PCI, BVS
displays acceptable intraindividual performance compared with DES. Larger trials,
extended follow-up, and continuous device iteration remain essential to improve
BVS technology.
PMID- 27512087
TI - Very Long-Term (10 to 14 Year) Outcomes After Percutaneous Coronary Intervention
Versus Coronary Artery Bypass Grafting for Multivessel Coronary Artery Disease in
the Bare-Metal Stent Era.
AB - BACKGROUND: Many of the previous randomized trials comparing percutaneous
coronary intervention (PCI) with coronary artery bypass grafting (CABG) in
patients with multivessel coronary artery disease reported equivalent or better
survival with CABG as compared with PCI at 5-year follow-up. However, 5-year
follow-up might be too short to evaluate the true differences in long-term
clinical outcomes between PCI and CABG. METHODS AND RESULTS: Among 8934 patients
enrolled in the extended 10- to 14-year follow-up study of the CREDO-Kyoto
registry cohort-1 (Coronary Revascularization Demonstrating Outcome study in
Kyoto) conducted in the bare-metal stent era, 5152 (PCI: n=3490 and CABG: n=1662)
patients had multivessel coronary artery disease without left main disease.
Median follow-up duration was 11.2 (interquartile range: 10.2-12.2) years. The
cumulative 10-year incidence of all-cause death was not significantly different
between PCI and CABG (32.2% versus 31.7%; log-rank P=0.93). After adjusting for
confounders, however, the mortality risk of PCI was significantly higher than
that of CABG (hazard ratio, 1.19 [95% confidence interval, 1.02-1.39]; P=0.03).
Within 5 years after the index procedure, the risk for all-cause death was
significantly higher after PCI than after CABG (hazard ratio, 1.41; 95% CI, 1.12
1.79; P=0.004). By a landmark analysis at 5 years, however, the cumulative 10
year incidence of and adjusted risk for all-cause death beyond 5 years were not
significantly different between PCI and CABG (19.3% versus 20.0%; log-rank P=0.22
and hazard ratio, 1.02, 95% confidence interval, 0.83-1.26; P=0.82). CONCLUSIONS:
CABG as compared with PCI was associated with better 10-year survival in patients
with multivessel coronary artery disease. However, the benefit of CABG compared
with PCI on late mortality beyond 5 years was not observed in this study.
PMID- 27512089
TI - Routine Endovascular Treatment With a Stent Graft for Access-Site and Access
Related Vascular Injury in Transfemoral Transcatheter Aortic Valve Implantation.
AB - BACKGROUND: Access-site and access-related vascular injury (ASARVI) is still a
major limiting factor in transcatheter aortic valve implantation and affects the
outcome of patients. Management strategies for ASARVI include manual compression,
stent grafts, and vascular surgery. We hypothesized that the standard use of a
self-expanding stent graft for the management of ASARVI is feasible and safe.
METHODS AND RESULTS: Of 407 patients treated by transfemoral transcatheter aortic
valve implantation, 110 experienced ASARVI (27.0%). Of these, 96 (87.3%) were
managed by the implantation of a self-expanding nitinol stent graft. In the
majority of patients, minor vascular complications triggered the implantation of
a stent graft (86.5%), mainly because of bleeding (90.6%) and dissection (5.2%)
of the common femoral artery with high rates of primary treatment success
(97.9%). Patients receiving stent grafts were more often female (62.2 versus
45.6%, P<0.01), had higher body mass indices (27.8+/-6.7 versus 25.7+/-4.7,
P=0.01), and suffered more often from diabetes mellitus (34.4 versus 24.5%,
P=0.04). Angiographic assessment after a median follow-up of 345 days
(interquartile range, 23-745 days) revealed only one patient with moderate,
asymptomatic instent-stenosis (1.0%). Compared with a propensity score-matched
cohort of patients without ASARVI, stented patients had comparable long-term
mortality, despite the occurrence of a vascular complication (1-year mortality:
17.7% versus 26.6%; stent versus matched cohort, respectively; P=0.1).
CONCLUSIONS: Routine use of a self-expanding nitinol stent graft in selected
patients experiencing ASARVI after transcatheter aortic valve implantation is
feasible, safe, and associated with favorable short- and midterm clinical
outcome.
PMID- 27512090
TI - Absorb Bioresorbable Vascular Scaffold in Complex Coronary Bifurcation
Interventions: Insights From an In Vivo Multimodality Imaging Study.
AB - BACKGROUND: Although bioresorbable scaffolds offer potential advantages compared
with metallic drug-eluting stents in the treatment of complex coronary
bifurcation lesions, there are concerns that the polymeric scaffold integrity may
be compromised. This in vivo study sought to provide insights about the
feasibility of performing complex bifurcation stenting with Absorb bioresorbable
vascular scaffolds (Abbott Vascular, Santa Clara, CA). METHODS AND RESULTS:
Twenty New Zealand white rabbits underwent stenting of the nondiseased aortoiliac
bifurcation with bioresorbable vascular scaffolds using provisional (PS, n=5),
culotte (n=5), modified-T (n=5), or T-and protrusion (n=5) stenting techniques.
Angiography, optical coherence tomography, and microcomputed tomography were
performed. Angiographic results were excellent without evidence of dissection or
side branch (SB) compromise. PS optimally opened the SB ostium without deforming
the main vessel (MV) bioresorbable vascular scaffolds, avoiding malapposition,
and revealing a single connector fracture in 1 of 5 cases on microcomputed
tomography. Culotte stenting resulted in complete bifurcation coverage with
extensive segments of double-layered struts and inappropriately apposed struts at
the bifurcation level in 3 of 5 cases. On microcomputed tomography, there was MV
and SB scaffold distortion at the bifurcation with single strut fractures in 4 of
5 and double fractures in 1 of 5. Modified-T and T-and protrusion resulted in
complete bifurcation coverage and in minimal double-strut layers at the
neocarina. On microcomputed tomography, no strut fractures were present after
modified-T, whereas in 3 of 5 T-and protrusion procedures single strut fractures
were noted. CONCLUSIONS: Bifurcation stenting using bioresorbable vascular
scaffolds is feasible with excellent angiographic results. PS with additional T
and protrusion whenever needed seems a reasonable approach. Whenever a 2-stent
technique is planned, modified T-stenting appears the most promising.
PMID- 27512091
TI - Antihypertensive Effects of a Central Arteriovenous Anastomosis Are Mediated
Through Profound Reduction in Systemic Vascular Resistance.
PMID- 27512092
TI - Towards a structure of feeling: abjection and allegories of disease in science
fiction 'mutation' films.
AB - This article considers differences between the representation of mutation in
science fiction films from the 1950s and the present, and identifies distinctive
changes over this time period, both in relation to the narrative causes of
genetic disruption and in the aesthetics of its visual display. Discerning an
increasingly abject quality to science fiction mutations from the 1970s onwards
as a progressive tendency to view the physically opened body, one that has a
seemingly fluid interior-exterior reversal, or one that is almost beyond
recognition as humanoid-the article connects a propensity for disgust to the
corresponding socio-cultural and political zeitgeist. Specifically, it suggests
that such imagery is tied to a more expansive 'structure of feeling', proposed by
Raymond Williams and emergent since the 1970s, but gathering momentum in later
decades, that reflects an 'opening up' of society in all its visual, socio
cultural and political configurations. Expressly, it parallels a change from a
repressive, patriarchal society that constructed medicine as infallible and male
doctors as omnipotent to one that is generally more liberated, transparent and
equitable. Engaging theoretically with the concept of a 'structure of feeling',
and critically with scientific, cinematic and cultural discourses, two post
1970s' 'mutation' films, The Fly (1986) and District 9 (2009), are considered in
relation to their pre-1970s' predecessors, and their aesthetics related to the
perceptions and articulations of the medical profession at their respective
historic moments, locating such instances within a broader medico-political
canvas.
PMID- 27512094
TI - Numerical investigation of the haemodynamics in the human fetal umbilical
vein/ductus venosus based on the experimental data.
AB - Abortion of the fetus due to a disease, in an early stage of pregnancy, has been
dramatically increased in the last decades. There is a still lack of knowledge on
the various types of diseases which lead fetus to a vulnerable circumstance. The
transport of oxygenated blood from the placenta to the human fetus has been an
important clinical feature in Doppler velocimetry studies, especially the ductus
venosus (DV). The DV connects intra-abdominal portion of the umbilical vein and
the inferior vena cava (IVC) at the inlet of the right atrium and is, therefore,
important when examining the fetus state of health. An abnormal flow in the DV
can indicate a fetal disease such as, chromosomal abnormalities, cardiac defect,
hypoxaemia and intrauterine growth restriction (IUGR). The blood flow in the
fetal circulation has not been investigated much in detail. The blood flow in the
fetal circulation provides necessary information for physician to make a suitable
decision on abortion or alternative medical practice before or even after birth.
The present study performed a comparative study to quantify the blood velocity in
DV by a combination approach based on 3D computational simulation and Doppler
measurement. The results showed that the velocity value in DV is significant and
can be considered as an indicator of any kind of disease in fetal. The nodal
displacement of the model was also analysed. It shows that DV tolerates a higher
level of displacement compared with the other regions of the model, whereas the
nodal pressure shows different results as the lowest values are located in DV.
PMID- 27512093
TI - Role of the prostaglandin E2 receptor agonists in TGF-beta1-induced mesangial
cell damage.
AB - PGE2 exerts its biological effect through binding to various EP receptors that
result inactivation of various signal transduction pathways. It also plays an
important role in mice glomerular mesangial cells (MCs) damage induced by
transforming growth factor-beta1 (TGF-beta1); however, the molecular mechanisms
remain unknown. In the present study, we tested the efficacy of four selective
agonists of PGE2 receptor, EP1A (17-phenyl trinor prostaglandin E2 ethyl amid),
EP2A (butaprost), EP3A (sulprostone) and EP4A (cay10580), on mice MCs. Compared
with the cAMP produced by TGF-beta1, additional pretreatment of EP3A decreased
the cAMP level. MCs treated with EP1A and EP3A augmented PGE2, cyclooxygenase-2
(COX-2), membrane-bound PGE synthase 1 (mPGES1), laminin (LN), connective tissue
growth factor (CTGF) and cyclin D1 expression stimulated by TGFbeta1. EP1A and
EP3A increased the number of cells in S+G2/M phase and reduced cells in G0/G1
phase. EP1 and EP3 agonists also strengthened TGFbeta1-induced mitogen-activated
protein kinase (p38MAPK) and extracellular-signal-regulated kinase 1/2 (ERK1/2)
phosphorylation. Whereas MCs treated with EP2A and EP4A weakened PGE2, COX-2,
mPGES1, LN, CTGF and cyclin D1 expression stimulated by TGFbeta1. EP2A and EP4A
decreased the number of cells in S+G2/M phase and increased cells in G0/G1 phase.
EP2 and EP4 agonists weakened TGFbeta1-induced p38MAPK and ERK1/2
phosphorylation. These findings suggest that PGE2 has an important role in the
progression of kidney disease via the EP1/EP3 receptor, whereas EP2 and EP4
receptors are equally important in preserving the progression of chronic kidney
failure. Thus, agonists of EP2 and EP4 receptors may provide a basis for treating
kidney damage induced by TGF-beta1.
PMID- 27512095
TI - IL-1beta/HMGB1 signalling promotes the inflammatory cytokines release via TLR
signalling in human intervertebral disc cells.
AB - Inflammation and cytokines have been recognized to correlate with intervertebral
disc (IVD) degeneration (IDD), via mediating the development of clinical signs
and symptoms. However, the regulation mechanism remains unclear. We aimed at
investigating the regulatory role of interleukin (IL)beta and high mobility group
box 1 (HMGB1) in the inflammatory response in human IVD cells, and then explored
the signalling pathways mediating such regulatory effect. Firstly, the promotion
to inflammatory cytokines in IVD cells was examined with ELISA method. And then
western blot and real time quantitative PCR were performed to analyse the
expression of toll-like receptors (TLRs), receptors for advanced glycation
endproducts (RAGE) and NF-kappaB signalling markers in the IL-1beta- or (and)
HMGB1-treated IVD cells. Results demonstrated that either IL-1beta or HMGB1
promoted the release of the inflammatory cytokines such as prostaglandin E2
(PGE2), TNF-alpha, IL-6 and IL-8 in human IVD cells. And the expression of matrix
metalloproteinases (MMPs) such as MMP-1, -3 and -9 was also additively up
regulated by IL-1beta and HMGB1. We also found such additive promotion to the
expression of TLR-2, TLR-4 and RAGE, and the NF-kappaB signalling in
intervertebral disc cells. In summary, our study demonstrated that IL-1beta and
HMGB1 additively promotes the release of inflammatory cytokines and the
expression of MMPs in human IVD cells. The TLRs and RAGE and the NF-kappaB
signalling were also additively promoted by IL-1beta and HMGB1. Our study implied
that the additive promotion by IL-1beta and HMGB1 to inflammatory cytokines and
MMPs might aggravate the progression of IDD.
PMID- 27512096
TI - Mechanisms for the inhibition of amyloid aggregation by small ligands.
AB - The formation of amyloid aggregates is the hallmark of systemic and
neurodegenerative disorders, also known as amyloidoses. Many proteins have been
found to aggregate into amyloid-like fibrils and this process is recognized as a
general tendency of polypeptides. Lysozyme, an antibacterial protein, is a well
studied model since it is associated in human with systemic amyloidosis and that
is widely available from chicken eggs (HEWL, hen egg white lysozyme). In the
present study we investigated the mechanism of interaction of aggregating HEWL
with rosmarinic acid and resveratrol, that we verified to be effective and
ineffective, respectively, in inhibiting aggregate formation. We used a
multidisciplinary strategy to characterize such effects, combining biochemical
and biophysical methods with molecular dynamics (MD) simulations on the HEWL
peptide 49-64 to gain insights into the mechanisms and energy variations
associated to amyloid formation and inhibition. MD revealed that neither
resveratrol nor rosmarinic acid were able to compete with the initial formation
of the beta-sheet structure. We then tested the association of two beta-sheets,
representing the model of an amyloid core structure. MD showed that rosmarinic
acid displayed an interaction energy and a contact map comparable to that of
sheet pairings. On the contrary, resveratrol association energy was found to be
much lower and its contact map largely different than that of sheet pairings. The
overall characterization elucidated a possible mechanism explaining why, in this
model, resveratrol is inactive in blocking fibril formation, whereas rosmarinic
acid is instead a powerful inhibitor.
PMID- 27512097
TI - Adipose-specific inactivation of JNK alleviates atherosclerosis in apoE-deficient
mice.
AB - Both atherosclerosis and obesity, an independent atherosclerotic risk factor, are
associated with enhanced systemic inflammation. Obesity is also characterized by
increased adipose tissue inflammation. However, the molecular mechanism
underlying the accelerated atherosclerosis in obesity remains unclear. In
obesity, activation of c-Jun N-terminal kinase (JNK) contributes to adipose
tissue inflammation. The present study investigated whether the suppression of
fat inflammation through adipose-specific JNK inactivation could protect against
atherosclerosis in mice. ApoE-/- mice were cross-bred with transgenic mice with
adipose-specific expression of a dominant negative form of JNK (dnJNK) to
generate apoE-/-/dnJNK (ADJ) mice. ADJ mice treated with a high-fat-high
cholesterol diet exhibited significant attenuations of visceral fat and systemic
inflammation without changes in lipid or glucose metabolism, and were protected
against atherosclerosis, when compared with apoE-/- mice. Lean apoE-/- mice that
received transplantation of visceral fat from obese wild-type donor mice for 4
weeks showed exacerbated systemic inflammation and atherosclerotic plaque
formation. Conversely, apoE-/- recipients carrying a visceral fat graft from
obese dnJNK donors were protected against enhanced systemic inflammation and
atherogenesis. The beneficial effects of adipose-specific JNK inactivation on
atherogenesis in apoE-/- recipients were significantly compromised by continuous
infusion of recombinant adipocyte-fatty acid-binding protein (A-FABP), previously
shown to interact with JNK via a positive feedback loop to modulate inflammatory
responses. Together these data suggested that enhanced atherosclerosis in obesity
can be attributed, at least in part, to a distant cross-talk between visceral fat
and the vasculature, mediated by the release of proinflammatory cytokines, such
as A-FABP, from the inflamed visceral adipose tissue with JNK activation.
PMID- 27512098
TI - Effectiveness and safety of Chinese massage therapy (Tui Na) on post-stroke
spasticity: a prospective multicenter randomized controlled trial.
AB - OBJECTIVE: To evaluate the effectiveness and safety of Chinese massage therapy
(Tui Na) for patients with post-stroke spasticity. DESIGN: A prospective,
multicenter, blinded, randomized, placebo-controlled intervention trial. SUBJECT:
A total of 90 patients with post-stroke spasticity were randomly assigned to the
experimental (Tui Na therapy) group ( n = 45) or control (placebo Tui Na therapy)
group ( n = 45). INTERVENTION: Participants in the experimental group received
Tui Na therapy, while those in the control group received placebo-Tai Na (gentle
rubbing) for 20-25 minutes per limb, once per day, five days per week for a total
of four weeks. All participants in both groups received conventional
rehabilitation. MAIN MEASURE: The Modified Ashworth Scale, the Fugl-Meyer
Assessment and the Modified Barthel Index were used to assess the severity of
spasticity, motor function of limbs and activities of daily living, respectively.
Assessments were performed at baseline, at four weeks and at three months.
RESULTS: Tui Na group had a significantly greater reduction in Modified Ashworth
Scale in only four muscle groups than the control did (elbow flexors, P = 0.026;
wrist flexors, P = 0.005; knee flexors, P = 0.023; knee extensors, P = 0.017).
Improvements were sustained at three months follow-up. There was no significant
difference between the two groups in Fugl-Meyer Assessment ( P = 0.503) and
Modified Barthel Index ( P = 0.544). No adverse reaction was recorded in any of
the cases mentioned at all study sites. CONCLUSIONS: Tui Na might be a safe and
effective treatment to reduce post-stroke spasticity of several muscle groups.
PMID- 27512099
TI - Water-based vs. non-water-based physiotherapy for rehabilitation of postural
deformities in Parkinson's disease: a randomized controlled pilot study.
AB - OBJECTIVE: To compare the efficacy of two physiotherapy protocols (water-based
vs. non-water-based) on postural deformities of patients with Parkinson's
disease. DESIGN: A single blind, randomized controlled pilot study. SETTING:
Inpatient (Rehabilitative Department). PARTICIPANTS: A total of 30 patients with
idiopathic Parkinson's disease. INTERVENTIONS: Participants were randomly
assigned to one of two eight-week treatment groups: Water-based ( n = 15) or non
water-based physiotherapy exercises ( n = 15). OUTCOME MEASURES: Changes in the
degree of cervical and dorsal flexion and in the angle of lateral inclination of
the trunk (evaluated by means of a posturographic system) were used as primary
outcomes. Unified Parkinson Disease Rating Scale section III, Time Up and Go
Test, Berg Balance Scale, Activities-specific Balance Confidence, Falls Efficacy
Scale and the Parkinson's disease quality of life questionnaire (39 items) were
the secondary outcomes. All outcomes were assessed at baseline, at the end of
training and eight weeks after treatment. Patients were always tested at the time
of their optimal antiparkinsonian medication ('on' phase). RESULTS: After the
treatment, only Parkinson's disease subjects randomized to water-based treatment
showed a significant improvement of trunk posture with a significant reduction of
cervical flexion (water-based group: -65.2 degrees ; non-water-based group: +1.7
degrees ) and dorsal flexion (water-based group: -22.5 degrees ; non-water-based
group: -6.5 degrees ) and lateral inclination of the trunk (water-based group:
2.3 degrees ; non-water-based group: +0.3 degrees ). Both groups presented
significant improvements in the secondary clinical outcomes without between-group
differences. CONCLUSION: Our results show that water-based physiotherapy was
effective for improving postural deformities in patients with Parkinson's
disease.
PMID- 27512101
TI - Correction for Chakroun et al., Bacterial Vegetative Insecticidal Proteins (Vip)
from Entomopathogenic Bacteria.
PMID- 27512100
TI - Lipoproteins of Gram-Positive Bacteria: Key Players in the Immune Response and
Virulence.
AB - Since the discovery in 1973 of the first of the bacterial lipoproteins (Lpp) in
Escherichia coli, Braun's lipoprotein, the ever-increasing number of publications
indicates the importance of these proteins. Bacterial Lpp belong to the class of
lipid-anchored proteins that in Gram-negative bacteria are anchored in both the
cytoplasmic and outer membranes and in Gram-positive bacteria are anchored only
in the cytoplasmic membrane. In contrast to the case for Gram-negative bacteria,
in Gram-positive bacteria lipoprotein maturation and processing are not vital.
Physiologically, Lpp play an important role in nutrient and ion acquisition,
allowing particularly pathogenic species to better survive in the host. Bacterial
Lpp are recognized by Toll-like receptor 2 (TLR2) of the innate immune system.
The important role of Lpp in Gram-positive bacteria, particularly in the phylum
Firmicutes, as key players in the immune response and pathogenicity has emerged
only in recent years. In this review, we address the role of Lpp in signaling and
modulating the immune response, in inflammation, and in pathogenicity. We also
address the potential of Lpp as promising vaccine candidates.
PMID- 27512102
TI - Implementation and de-implementation: two sides of the same coin?
AB - Avoiding low value care received increasing attention in many countries, as with
the Choosing Wisely campaign and other initiatives to abandon care that wastes
resources or delivers no benefit to patients. While an extensive literature
characterises approaches to implementing evidence-based care, we have limited
understanding of the process of de-implementation, such as abandoning existing
low value practices. To learn more about the differences between implementation
and de-implementation, we explored the literature and analysed data from two
published studies (one implementation and one de-implementation) by the same
orthopaedic surgeons. We defined 'leaders' as those orthopaedic surgeons who
implemented, or de-implemented, the target processes of care and laggards as
those who did not. Our findings suggest that leaders in implementation share some
characteristics with leaders in de-implementation when comparing them with
laggards, such as more open to new evidence, younger and less time in clinical
practice. However, leaders in de-implementation and implementation differed in
some other characteristics and were not the same persons. Thus, leading in
implementation or de-implementation may depend to some degree on the type of
intervention rather than entirely reflecting personal characteristics. De
implementation seemed to be hampered by motivational factors such as department
priorities, and economic and political factors such as cost-benefit
considerations in care delivery, whereas organisational factors were associated
only with implementation. The only barrier or facilitator common to both
implementation and de-implementation consisted of outcome expectancy (ie, the
perceived net benefit to patients). Future studies need to test the hypotheses
generated from this study and improve our understanding of differences between
the processes of implementation and de-implementation in the people who are most
likely to lead (or resist) these efforts.
PMID- 27512103
TI - Differential Response to Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart
Failure With Reduced or Preserved Ejection Fraction: Results From the ROSE AHF
Trial (Renal Optimization Strategies Evaluation in Acute Heart Failure).
AB - BACKGROUND: The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute
Heart Failure) found that when compared with placebo, neither low-dose dopamine
(2 ug/kg per minute) nor low-dose nesiritide (0.005 MUg/kg per minute without
bolus) enhanced decongestion or preserved renal function in AHF patients with
renal dysfunction. However, there may be differential responses to vasoactive
agents in AHF patients with reduced versus preserved ejection fraction (EF). This
post hoc analysis examined potential interaction between treatment effect and EF
(EF <=40% versus >40%) on the ROSE AHF end points. METHODS AND RESULTS: ROSE AHF
enrolled AHF patients (n=360; any EF) with renal dysfunction. The coprimary end
points were cumulative urine volume and the change in serum cystatin-C in 72
hours. The effect of dopamine (interaction P=0.001) and nesiritide (interaction
P=0.039) on urine volume varied by EF group. In heart failure with reduced EF,
urine volume was higher with active treatment versus placebo, whereas in heart
failure with preserved EF, urine volume was lower with active treatment. The
effect of dopamine and nesiritide on weight change, sodium excretion, and
incidence of AHF treatment failure also varied by EF group (interaction P<0.05
for all). There was no interaction between vasoactive treatment's effect and EF
on change in cystatin-C. Compared with placebo, dopamine was associated with
improved clinical outcomes in heart failure with reduced EF and worse clinical
outcomes in heart failure with preserved EF. With nesiritide, there were no
differences in clinical outcomes when compared with placebo in both heart failure
with reduced EF and heart failure with preserved EF. CONCLUSIONS: In this post
hoc analysis of ROSE AHF, the response to vasoactive therapies differed in
patients with heart failure with reduced EF and heart failure with preserved EF.
Investigations of AHF therapies should assess the potential for differential
responses in AHF with preserved versus reduced EF. CLINICAL TRIAL REGISTRATION:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01132846.
PMID- 27512105
TI - BREXIT and science, where do we go from here.
PMID- 27512104
TI - Association of Weight and Body Composition on Cardiac Structure and Function in
the ARIC Study (Atherosclerosis Risk in Communities).
AB - BACKGROUND: Obesity increases cardiovascular risk. However, the extent to which
various measures of body composition are associated with abnormalities in cardiac
structure and function, independent of comorbidities commonly affecting obese
individuals, is not clear. This study sought to examine the relationship between
body mass index, waist circumference, and percent body fat with conventional and
advanced measures of cardiac structure and function. METHODS AND RESULTS: We
studied 4343 participants of the ARIC study (Atherosclerosis Risk in Communities)
who were aged 69 to 82 years, free of coronary heart disease and heart failure,
and underwent comprehensive echocardiography. Increasing body mass index, waist
circumference, and body fat were associated with greater left ventricular (LV)
mass and left atrial volume indexed to height(2.7) in both men and women
(P<0.001). In women, all 3 measures were associated with abnormal LV geometry,
and increasing waist circumference and body fat were associated with worse global
longitudinal strain, a measure of LV systolic function. In both sexes, increasing
body mass index was associated with greater right ventricular end-diastolic area
and worse right ventricular fractional area change (P<=0.001). We observed
similar associations for both waist circumference and percent body fat.
CONCLUSIONS: In a large, biracial cohort of older adults free of clinically overt
coronary heart disease or heart failure, obesity was associated with subclinical
abnormalities in cardiac structure in both men and women and with adverse LV
remodeling and impaired LV systolic function in women. These data highlight the
association of obesity and subclinical abnormalities of cardiac structure and
function, particularly in women.
PMID- 27512106
TI - Precision medicine in idiopathic pulmonary fibrosis.
PMID- 27512107
TI - Spectrum and outcome of acute infectious encephalitis/encephalopathy in an
intensive care unit from India.
AB - Purpose: To evaluate the spectrum of acute infectious encephalitis/encephalopathy
syndrome (AIES) in intensive care unit (ICU) and the predictors of mechanical
ventilation (MV) and outcome of these patients. Methods: AIES patients diagnosed
on the basis of fever, altered sensorium, seizure and cerebrospinal fluid
pleocytosis admitted to the neurology ICU were prospectively included. The
demographic and clinical details, hematological, biochemical, MRI and etiological
findings of the patients were noted. Need of MV, death in hospital and 3-month
functional outcome were analyzed. Results: One hundred sixty-four out of 258
(64%) AIES patients needed ICU admission. Their median age was 35 (2-85) years
and 71 (43%) were females. The etiology was viral in 44 (herpes and Japanese
encephalitis in 12 each, dengue in 17, mumps, measles and varicella in 1 patient
each), non-viral in 64 (scrub typhus in 48, falciparum malaria in 6, leptospira
in 3 and bacterial in 7) and undetermined etiology in 56 (34%) patients. Sixty
nine (42%) patients needed MV. On multivariate analysis, Glasgow Coma Scale (GCS)
score, Sequential Organ Failure Assessment (SOFA) score and raised intracranial
pressure were independent predictors of MV. Forty-three (26%) patients died, and
all were in the MV group. Higher SOFA score and untreatable etiology were
independent predictors of mortality. At 3-month follow-up, 14% had poor and 86%
had good outcome. Low GCS score, focal weakness and status epilepticus
independently predicted poor outcome. Conclusion: Twenty-six percent patients
with AIES died in ICU, and 86% had good recovery at 3 months. Admission SOFA
scores and untreatable etiology predicted mortality.
PMID- 27512109
TI - Trajectories of Risk Factors and Risk of New-Onset Atrial Fibrillation in the
Framingham Heart Study.
AB - The associations of long-term patterns of risk factors and the risk of incident
atrial fibrillation (AF) are incompletely characterized. Among 4351 Framingham
Study participants (mean age 50+/-11 years at baseline examination, 57% women)
from the original and offspring cohorts, we defined longitudinal patterns,
referred to as trajectories, of AF risk factors and a composite AF risk score
using ~16 years of data. We used Cox proportional hazards models to examine the
association of trajectories to 15-year risk of AF. During follow-up, 719
participants developed AF. Five distinct trajectory groups were identified for
systolic blood pressure (BP): groups 1 and 2 (normotensive throughout), group 3
(prehypertensive), group 4 (hypertensive initially with decreasing BP), and group
5 (hypertensive and increasing BP). In multivariable-adjusted analyses, compared
with group 1, groups 4 (hazard ratio 2.05; 95% confidence interval 1.24-3.37) and
5 (hazard ratio 1.95; 95% confidence interval 1.08-3.49) were associated with
incident AF. Three trajectory groups were identified for antihypertensive
treatment. Compared with the group with no treatment throughout, the other 2
groups were associated with increased risk of incident AF. Distinct trajectories
for diastolic BP, smoking, diabetes mellitus, and the composite risk score were
not associated with increased 15-year risk of AF. Longitudinal trajectories may
distinguish how exposures related to AF contribute toward prospective AF risk.
Distinct trajectory groups with persistently elevated systolic BP and longer
antihypertensive treatment are associated with increased risk of incident AF.
PMID- 27512110
TI - Establishing an injury indicator for severe paediatric injury.
AB - BACKGROUND: Routinely gathered injury data, such as hospitalisations, may be
subject to variation from sources other than injury incidence. There is a need
for an indicator that defines severe injury, which may be less vulnerable to
fluctuations due to changes in care policies. The purpose of this study was to
identify International Classification of Diseases-10 codes associated with severe
paediatric injuries and to specify and validate a severe paediatric injury
indicator. METHODS: Two data sets that included the ISS and the survival risk
ratio were used to produce a list of diagnoses to define severe paediatric
injury. The list was sent to trauma surgeons who classified each code as severe
enough or not severe enough to require care in a trauma centre. The indicator was
fully specified, then validated by using a different data set to validate the
codes in a real-world situation. RESULTS: Sixty diagnoses were identified as
representing severe paediatric injury. Following specification, the indicator was
applied to an existing comprehensive data set of paediatric injuries. The decline
in hospitalisation of paediatric injuries was significantly steeper for severe
than non-severe injuries, suggesting that factors related to the decline in this
trauma subset are unlikely to be related to changes in access or other components
of trauma care delivery. CONCLUSIONS: This indicator can be used for the
evaluation of trends in severe paediatric trauma and will help identify
populations at risk. This research may inform policies and procedures for
referrals of severe childhood injury to appropriate levels of care.
PMID- 27512111
TI - Unusual Diversity of Myoglobin Genes in the Lungfish.
AB - Myoglobin is a respiratory protein that serves as a model system in a variety of
biological fields. Its main function is to deliver and store O2 in the heart and
skeletal muscles, but myoglobin is also instrumental in homeostasis of nitric
oxide (NO) and detoxification of reactive oxygen species (ROS). Almost every
vertebrate harbors a single myoglobin gene; only some cyprinid fishes have two
recently duplicated myoglobin genes. Here we show that the West African lungfish
Protopterus annectens has at least seven distinct myoglobin genes (PanMb1-7),
which diverged early in the evolution of lungfish and showed an enhanced
evolutionary rate. These myoglobins are lungfish specific, and no other globin
gene was found amplified. The myoglobins are differentially expressed in various
lungfish tissues, and the brain is the main site of myoglobin expression. The
typical myoglobin-containing tissues, the skeletal muscle and the heart, have
much lower myoglobin mRNA levels. Muscle and heart express distinct myoglobins
(PanMb1 and PanMb3, respectively). In cell culture, lungfish myoglobins improved
cellular survival under hypoxia albeit with different efficiencies and reduced
the production of reactive oxygen species. Only Mb2 and Mb6 enhanced the energy
status of the cells. The unexpected diversity of myoglobin hints to a functional
diversification of this gene: some myoglobins may have adapted to the O2
requirements of the specific tissue and help the lungfish to survive hypoxic
periods; other myoglobins may have taken over the roles of neuroglobin and
cytoglobin, which appear to be missing in the West African lungfish.
PMID- 27512112
TI - Positive Selection Drives Evolution at the Host-Filovirus Interaction Surface.
AB - Filovirus infection is mediated by engagement of the surface-exposed glycoprotein
(GP) by its cellular receptor, NPC1 (Niemann-Pick C1). Two loops in the C domain
of NPC1 (NPC1-C) bind filovirus GP. Herein, we show that filovirus GP and NPC1-C
evolve under mutual selective pressure. Analysis of a large mammalian phylogeny
indicated that strong functional/structural constraints limit the NPC1 sequence
space available for adaptive change and most sites at the contact interface with
GP are under negative selection. These constraints notwithstanding, we detected
positive selection at NPC1-C in all mammalian orders, from Primates to Xenarthra.
Different codons evolved adaptively in distinct mammals, and most selected sites
are located within the two NPC1-C loops that engage GP, or at their anchor
points. In Homininae, NPC1-C was a preferential selection target, and the T419I
variant possibly represents a human-specific adaptation to filovirus infection.
On the other side of the arms-race, GP evolved adaptively during filovirus
speciation. One of the selected sites (S142Q) establishes several atom-to-atom
contacts with NPC1-C. Additional selected sites are located within epitopes
recognized by neutralizing antibodies, including the 14G7 epitope, where sites
selected during the recent EBOV epidemic also map. Finally, pairs of co-evolving
sites in Marburgviruses and Ebolaviruses were found to involve antigenic
determinants. These findings suggest that the host humoral immune response was a
major selective pressure during filovirus speciation. The S142Q variant may
contribute to determine Ebolavirus host range in the wild. If this were the case,
EBOV/BDBV (S142) and SUDV (Q142) may not share the same reservoir(s).
PMID- 27512113
TI - A Phylogenomic Framework to Study the Diversity and Evolution of Stramenopiles
(=Heterokonts).
AB - Stramenopiles or heterokonts constitute one of the most speciose and diverse
clades of protists. It includes ecologically important algae (such as diatoms or
large multicellular brown seaweeds), as well as heterotrophic (e.g., bicosoecids,
MAST groups) and parasitic (e.g., Blastocystis, oomycetes) species. Despite their
evolutionary and ecological relevance, deep phylogenetic relationships among
stramenopile groups, inferred mostly from small-subunit rDNA phylogenies, remain
unresolved, especially for the heterotrophic taxa. Taking advantage of recently
released stramenopile transcriptome and genome sequences, as well as data from
the genomic assembly of the MAST-3 species Incisomonas marina generated in our
laboratory, we have carried out the first extensive phylogenomic analysis of
stramenopiles, including representatives of most major lineages. Our analyses,
based on a large data set of 339 widely distributed proteins, strongly support a
root of stramenopiles lying between two clades, Bigyra and Gyrista (Pseudofungi
plus Ochrophyta). Additionally, our analyses challenge the Phaeista-Khakista
dichotomy of photosynthetic stramenopiles (ochrophytes) as two groups previously
considered to be part of the Phaeista (Pelagophyceae and Dictyochophyceae),
branch with strong support with the Khakista (Bolidophyceae and Diatomeae). We
propose a new classification of ochrophytes within the two groups Chrysista and
Diatomista to reflect the new phylogenomic results. Our stramenopile phylogeny
provides a robust phylogenetic framework to investigate the evolution and
diversification of this group of ecologically relevant protists.
PMID- 27512114
TI - Recombination Rate Variation, Hitchhiking, and Demographic History Shape
Deleterious Load in Poplar.
AB - Deleterious alleles are expected to be purged by purifying selection or
maintained at low frequency. However, many additional evolutionary forces may
shape the pattern of deleterious mutations across the genome and among
populations, including selection, hitchhiking, recombination, and demographic
history. We used exome capture data to estimate the genome-wide distribution of
deleterious alleles across natural populations of the model tree black cottonwood
(Populus trichocarpa). Although deleterious alleles were on average present at
low frequency suggesting purifying selection, they were preferentially enriched
both within genomic regions of low-recombination and in regions showing evidence
of positive selection. The demographic history of this species also appeared to
play a role in the distribution of deleterious alleles among populations, with
peripheral populations having higher rates of deleterious homozygosity. This be
due to less efficient selection arising from smaller effective population sizes
at the edges of the range, and possibly also due to recent bottlenecks associated
with postglacial recolonization. Finally, correlations between deleterious
homozygosity and plant growth suggest a significant effect of deleterious load on
fitness. Our results show that both genomic context and historical demography
play a role in shaping the distribution of deleterious alleles across the genome
and range of P. trichocarpa.
PMID- 27512115
TI - Extensively Parameterized Mutation-Selection Models Reliably Capture Site
Specific Selective Constraint.
AB - The mutation-selection model of coding sequence evolution has received renewed
attention for its use in estimating site-specific amino acid propensities and
selection coefficient distributions. Two computationally tractable mutation
selection inference frameworks have been introduced: One framework employs a
fixed-effects, highly parameterized maximum likelihood approach, whereas the
other employs a random-effects Bayesian Dirichlet Process approach. While both
implementations follow the same model, they appear to make distinct predictions
about the distribution of selection coefficients. The fixed-effects framework
estimates a large proportion of highly deleterious substitutions, whereas the
random-effects framework estimates that all substitutions are either nearly
neutral or weakly deleterious. It remains unknown, however, how accurately each
method infers evolutionary constraints at individual sites. Indeed, selection
coefficient distributions pool all site-specific inferences, thereby obscuring a
precise assessment of site-specific estimates. Therefore, in this study, we use a
simulation-based strategy to determine how accurately each approach recapitulates
the selective constraint at individual sites. We find that the fixed-effects
approach, despite its extensive parameterization, consistently and accurately
estimates site-specific evolutionary constraint. By contrast, the random-effects
Bayesian approach systematically underestimates the strength of natural
selection, particularly for slowly evolving sites. We also find that, despite the
strong differences between their inferred selection coefficient distributions,
the fixed- and random-effects approaches yield surprisingly similar inferences of
site-specific selective constraint. We conclude that the fixed-effects mutation
selection framework provides the more reliable software platform for model
application and future development.
PMID- 27512116
TI - The Diversification of Plant NBS-LRR Defense Genes Directs the Evolution of
MicroRNAs That Target Them.
AB - High expression of plant nucleotide binding site leucine-rich repeat (NBS-LRR)
defense genes is often lethal to plant cells, a phenotype perhaps associated with
fitness costs. Plants implement several mechanisms to control the transcript
level of NBS-LRR defense genes. As negative transcriptional regulators, diverse
miRNAs target NBS-LRRs in eudicots and gymnosperms. To understand the
evolutionary benefits of this miRNA-NBS-LRR regulatory system, we investigated
the NBS-LRRs of 70 land plants, coupling this analysis with extensive small RNA
data. A tight association between the diversity of NBS-LRRs and miRNAs was found.
The miRNAs typically target highly duplicated NBS-LRRs In comparison, families of
heterogeneous NBS-LRRs were rarely targeted by miRNAs in Poaceae and Brassicaceae
genomes. We observed that duplicated NBS-LRRs from different gene families
periodically gave birth to new miRNAs. Most of these newly emerged miRNAs target
the same conserved, encoded protein motif of NBS-LRRs, consistent with a model of
convergent evolution for these miRNAs. By assessing the interactions between
miRNAs and NBS-LRRs, we found nucleotide diversity in the wobble position of the
codons in the target site drives the diversification of miRNAs. Taken together,
we propose a co-evolutionary model of plant NBS-LRRs and miRNAs hypothesizing how
plants balance the benefits and costs of NBS-LRR defense genes.
PMID- 27512117
TI - BPR1J373, an Oral Multiple Tyrosine Kinase Inhibitor, Targets c-KIT for the
Treatment of c-KIT-Driven Myeloid Leukemia.
AB - Acute myelogenous leukemia (AML) carrying t(8;21)(q22;q22) or
inv(16)/t(16;16)(p13;q22) is classified as core binding factor (CBF)-AML and
accounts for approximately 15% of AML. c-KIT mutation can be detected in 17%~46%
of CBF-AML and is associated with poor prognosis. c-KIT mutation is a crucial hit
and cooperates with AML1-ETO resulting from t(8;21)(q22;q22) to cause overt AML.
Tyrosine kinase inhibitors (TKI) targeting c-KIT, such as imatinib, has been used
successfully to treat c-KIT driven gastrointestinal stromal tumors. However, the
effect of TKI on c-KIT-driven leukemia, including CBF-AML and systemic
mastocytosis (SM), has not been satisfactory. BPR1J373 is a 5-phenylthiazol-2
ylamine-pyriminide derivative targeting multiple tyrosine kinases. It was shown
to inhibit cell proliferation and induce apoptosis in AML cells with
constitutively activated c-KIT via inhibiting c-KIT phosphorylation and its
downstream signals. The compound induced apoptosis by the mitochondrial intrinsic
pathway through upregulation of proapoptotic proteins Bax and Bak and caspase 8
and 9 activation in c-KIT mutant Kasumi-1 cells. Furthermore, it induced cell
cycle arrest via targeting aurora kinase B in c-KIT wild-type KG-1 cells. The
antitumor response of BPR1J373 was also shown in subcutaneously grafted SCID
mice. BPR1J373 was shown to effectively suppress c-KIT phosphorylation of D816V
mutation by treating c-KIT-null COS-1 cells transfected with c-KIT D816V mutant
plasmid. In conclusion, BPR1J373 inhibits cell proliferation of c-KIT-driven AML
cells via induction of apoptosis and cell-cycle arrest. It is also effective for
multiple drug-resistant c-KIT D816V mutation. BPR1J373 deserves further
development for clinical use in c-KIT-driven myeloid leukemia. Mol Cancer Ther;
15(10); 2323-33. (c)2016 AACR.
PMID- 27512118
TI - Trabectedin Is Active against Malignant Pleural Mesothelioma Cell and Xenograft
Models and Synergizes with Chemotherapy and Bcl-2 Inhibition In Vitro.
AB - Malignant pleural mesothelioma (MPM) is characterized by widespread resistance to
systemic therapy. Trabectedin is an antineoplastic agent targeting both the
malignant cells and the tumor microenvironment that has been approved for the
treatment of advanced soft tissue sarcoma and ovarian cancer. In this preclinical
study, we evaluated the antineoplastic potential of trabectedin as a single agent
and in drug combination approaches in human MPM. Therefore, we utilized an
extended panel of MPM cell lines (n = 6) and primary cell cultures from surgical
MPM specimens (n = 13), as well as nonmalignant pleural tissue samples (n = 2).
Trabectedin exerted a dose-dependent cytotoxic effect in all MPM cell cultures in
vitro when growing as adherent monolayers or nonadherent spheroids with IC50
values <= 2.6 nmol/L. Nonmalignant mesothelial cells were significantly less
responsive. The strong antimesothelioma activity was based on cell-cycle
perturbation and apoptosis induction. The activity of trabectedin against MPM
cells was synergistically enhanced by coadministration of cisplatin, a drug
routinely used for systemic MPM treatment. Comparison of gene expression
signatures indicated an inverse correlation between trabectedin response and bcl
2 expression. Accordingly, bcl-2 inhibitors (Obatoclax, ABT-199) markedly
synergized with trabectedin paralleled by deregulated expression of the bcl-2
family members bcl-2, bim, bax, Mcl-1, and bcl-xL as a consequence of trabectedin
exposure. In addition, trabectedin exerted significant antitumor activity against
an intraperitoneal MPM xenograft model. Together, these data suggest that
trabectedin exerts strong activity in MPM and synergizes with chemotherapy and
experimental bcl-2 inhibitors in vitro Thus, it represents a promising new
therapeutic option for MPM. Mol Cancer Ther; 15(10); 2357-69. (c)2016 AACR.
PMID- 27512119
TI - CXC Chemokine Receptor 3 Alternative Splice Variants Selectively Activate
Different Signaling Pathways.
AB - The G protein-coupled receptor (GPCR) C-X-C chemokine receptor 3 (CXCR3) is a
potential drug target that mediates signaling involved in cancer metastasis and
inflammatory diseases. The CXCR3 primary transcript has three potential
alternative splice variants and cell-type specific expression results in receptor
variants that are believed to have different functional characteristics. However,
the molecular pharmacology of ligand binding to CXCR3 alternative splice variants
and their downstream signaling pathways remain poorly explored. To better
understand the role of the functional consequences of alternative splicing of
CXCR3, we measured signaling in response to four different chemokine ligands
(CXCL4, CXCL9, CXCL10, and CXCL11) with agonist activity at CXCR3. Both CXCL10
and CXCL11 activated splice variant CXCR3A. Whereas CXCL10 displayed full
agonistic activity for Galphai activation and extracellular signal regulated
kinase (ERK) 1/2 phosphorylation and partial agonist activity for beta-arrestin
recruitment, CXCL9 triggered only modest ERK1/2 phosphorylation. CXCL11 induced
CXCR3B-mediated beta-arrestin recruitment and little ERK phosphorylation.
CXCR3Alt signaling was limited to modest ligand-induced receptor internalization
and ERK1/2 phosphorylation in response to chemokines CXCL11, CXCL10, and CXCL9.
These results show that CXCR3 splice variants activate different signaling
pathways and that CXCR3 variant function is not redundant, suggesting a mechanism
for tissue specific biased agonism. Our data show an additional layer of
complexity for chemokine receptor signaling that might be exploited to target
specific CXCR3 splice variants.
PMID- 27512120
TI - Human granulosa-luteal cells initiate an innate immune response to pathogen
associated molecules.
AB - The microenvironment of the ovarian follicle is key to the developmental success
of the oocyte. Minor changes within the follicular microenvironment can
significantly disrupt oocyte development, compromising the formation of competent
embryos and reducing fertility. Previously described as a sterile environment,
the ovarian follicle of women has been shown to contain colonizing bacterial
strains, whereas in domestic species, pathogen-associated molecules are
concentrated in the follicular fluid of animals with uterine infection. The aim
of this study is to determine whether human granulosa-luteal cells mount an
innate immune response to pathogen-associated molecules, potentially disrupting
the microenvironment of the ovarian follicle. Human granulosa-luteal cells were
collected from patients undergoing assisted reproduction. Cells were cultured in
the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h.
Supernatants and total RNA were collected for assessment by PCR and ELISA.
Granulosa-luteal cells were shown to express the molecular machinery required to
respond to a range of pathogen-associated molecules. Expression of TLR4 varied up
to 15-fold between individual patients. Granulosa-luteal cells increased the
expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of
the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the
expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR
expression were observed in granulosa-luteal cells following challenge, a
significant reduction in progesterone secretion was measured after treatment with
FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to
respond to pathogen-associated molecules and generate an innate immune response.
PMID- 27512121
TI - Only a small population of adult Sertoli cells actively proliferates in culture.
AB - Adult mammalian Sertoli cells (SCs) have been considered to be quiescent terminal
differentiated cells for many years, but recently, proliferation of adult SCs was
demonstrated in vitro and in vivo We further examined mouse SC behavior in
culture and found that there are two populations of adult SCs. The first
population is SCs from seminiferous tubules that hardly proliferate in vitro The
second population is small and consists of SCs with atypical nuclear morphology
from the terminal segments of seminiferous tubules, a transitional zone (TZ). TZ
SCs multiply in culture and form colonies, display mixture of mature and immature
SC characteristics, and generate cord-like structures in a collagen matrix. The
specific features of TZ SCs are ACTA2 expression in vitro and DMRT1 low levels in
vivo and in vitro Although the in vivo function of TZ SCs still remains unclear,
this finding has significant implications for our understanding of SC
differentiation and functioning in adult mammals.
PMID- 27512122
TI - Elucidating human male germ cell development by studying germ cell cancer.
AB - Human germ cell development is regulated in a spatio-temporal manner by complex
regulatory networks. Here, we summarize results obtained in germ cell tumors and
respective cell lines and try to pinpoint similarities to normal germ cell
development. This comparison allows speculating about the critical and error
prone mechanisms, which when disturbed, lead to the development of germ cell
tumors. Short after specification, primordial germ cells express markers of
pluripotency, which, in humans, persists up to the stage of fetal/infantile
spermatogonia. Aside from the rare spermatocytic tumors, virtually all seminomas
and embryonal carcinomas express markers of pluripotency and show signs of
pluripotency or totipotency. Therefore, it appears that proper handling of the
pluripotency program appears to be the most critical step in germ cell
development in terms of tumor biology. Furthermore, data from mice reveal that
germline cells display an epigenetic signature, which is highly similar to
pluripotent cells. This signature (poised histone code, DNA hypomethylation) is
required for the rapid induction of toti- and pluripotency upon fertilization. We
propose that adult spermatogonial cells, when exposed to endocrine disruptors or
epigenetic active substances, are prone to reinitiate the pluripotency program,
giving rise to a germ cell tumor. The fact that pluripotent cells can be derived
from adult murine and human testicular cells further corroborates this idea.
PMID- 27512123
TI - Oviductal response to gametes and early embryos in mammals.
AB - The oviduct is a complex and organized thin tubular structure connecting the
ovary with the uterus. It is the site of final sperm capacitation, oocyte
fertilization and, in most species, the first 3-4days of early embryo
development. The oviductal epithelium is made up of ciliary and secretory cells
responsible for the secretion of proteins and other factors which contribute to
the formation of the oviductal fluid. Despite significant research, most of the
pathways and oviductal factors implicated in the crosstalk between gametes/early
embryo and the oviduct remain unknown. Therefore, studying the oviductal
environment is crucial to improve our understanding of the regulatory mechanisms
controlling fertilization and embryo development. In vitro systems are a valuable
tool to study in vivo pathways and mechanisms, particularly those in the oviducts
which in livestock species are challenging to access. In studies of gamete and
embryo interaction with the reproductive tract, oviductal epithelial cells,
oviductal fluid and microvesicles co-cultured with gametes/embryos represent the
most appropriate in vitro models to mimic the physiological conditions in vivo.
PMID- 27512124
TI - 3'READS+, a sensitive and accurate method for 3' end sequencing of polyadenylated
RNA.
AB - Sequencing of the 3' end of poly(A)(+) RNA identifies cleavage and
polyadenylation sites (pAs) and measures transcript expression. We previously
developed a method, 3' region extraction and deep sequencing (3'READS), to
address mispriming issues that often plague 3' end sequencing. Here we report a
new version, named 3'READS+, which has vastly improved accuracy and sensitivity.
Using a special locked nucleic acid oligo to capture poly(A)(+) RNA and to remove
the bulk of the poly(A) tail, 3'READS+ generates RNA fragments with an optimal
number of terminal A's that balance data quality and detection of genuine pAs.
With improved RNA ligation steps for efficiency, the method shows much higher
sensitivity (over two orders of magnitude) compared to the previous version.
Using 3'READS+, we have uncovered a sizable fraction of previously overlooked pAs
located next to or within a stretch of adenylate residues in human genes and more
accurately assessed the frequency of alternative cleavage and polyadenylation
(APA) in HeLa cells (~50%). 3'READS+ will be a useful tool to accurately study
APA and to analyze gene expression by 3' end counting, especially when the amount
of input total RNA is limited.
PMID- 27512125
TI - Monitoring maternal and newborn health outcomes in Bauchi State, Nigeria: an
evaluation of a standards-based quality improvement intervention.
AB - OBJECTIVE: This study assessed the correlation between compliance with set
performance standards and maternal and neonatal deaths in health facilities.
DESIGN: Baseline and three annual follow-up assessments were conducted, and each
was followed by a quality improvement initiative using the Standards Based
Management and Recognition (SBM-R) approach. SETTING: Twenty-three secondary
health facilities of Bauchi state, Nigeria. PARTICIPANTS: Health care workers and
maternity unit patients. MAIN OUTCOME MEASURES: We examined trends in: (i)
achievement of SBM-R set performance standards based on annual assessment data,
(ii) the use of maternal and newborn health (MNH) service delivery practices
based on data from health facility registers and supportive supervision and (iii)
MNH outcomes based on routine service statistics. RESULTS: At the baseline
assessment in 2010, the facilities achieved 4% of SBM-R standards for MNH, on
average, and this increased to 86% in 2013. Over the same time period, the study
measured an increase in the administration of uterotonic for active management of
third stage of labor from 10% to 95% and a decline in the incidence of postpartum
hemorrhage from 3.3% to 1.9%. Institutional neonatal mortality rate decreased
from 9 to 2 deaths per 1000 live births, while the institutional maternal
mortality ratio dropped from 4113 to 1317 deaths per 100 000 live births.
CONCLUSION: Scaling up SBM-R for quality improvement has the potential to prevent
maternal and neonatal deaths in Nigeria and similar settings.
PMID- 27512126
TI - Assessing the impact of general practitioner team service on perceived quality of
care among patients with non-communicable diseases in China: a natural
experimental study.
AB - OBJECTIVE: China issued the national primary care policy of promoting general
practitioner (GP) team service in 2011. We conducted this study to assess the
impact of the GP team service on quality of primary care as perceived by patients
with non-communicable diseases (NCDs). DESIGN: Natural experimental study.
SETTING: This study was conducted in Shanghai, where the policy was effectively
implemented, and Kunming, where the policy was not implemented. PARTICIPANTS: In
both cities, NCD patients were interviewed with primary care assessment tool
(PCAT) after their clinical consultations in their community health centers.
INTERVENTION: The implementation of GP team service policy. MAIN OUTCOME
MEASURES: Multiple linear regressions were employed to compare PCAT scores
between the two rounds of the surveys in each city. Difference-in-difference
(DID) analysis was used to identify the changes between two cities over time.
RESULTS: A total of 663 and 587 patients in Shanghai, and 400 and 441 patients in
Kunming were surveyed in 2011 and 2013, respectively. The DID analysis showed
that the total primary care quality scores improved in Shanghai compared with
Kunming between 2011 and 2013 (beta = 1.30, 95% CI: 0.74, 1.87). In Shanghai,
care quality in 2013 improved significantly for the total score and the six
components when compared with those in 2011. No significant changes were observed
in Kunming in the same period. CONCLUSION: Primary care policies that promote
long-term provider-patient relationships, coordinated service with hospitals and
capitation payment for the GP team may contribute to the improvement of care
quality in Shanghai.
PMID- 27512127
TI - Guidance on how to achieve comprehensible patient information leaflets in four
steps.
AB - Comprehensible information leaflets can improve a patient's knowledge. However,
in clinical studies leaflets are often introduced without meticulously verifying
their comprehensibility. In an attempt to provide a feasible guidance on how to
design comprehensible leaflets we complied and evaluated an easy-to-use
development procedure. In January 2015, a literature search was performed to
identify evidence for readily available quality assurance strategies as a
starting point for a standardized strategy to develop and validate written
patient information. The suggested development strategy is a consecutive four
step procedure that comprised already validated distinct quality assessments: (i)
an initial requirement analysis specifying the needs and constraints of the
target population and evidence-based preparation of the leaflets, (ii) a
readability assessment, (iii) the Suitability Assessment of Materials instrument
and (iv) iterative consumer test in the target population. The consecutive
combination of pertinent and previously validated quality assessments provides an
easy-to-use guidance on how to create comprehensibly written patient information,
particularly for small-scale research projects with time and money constraints.
PMID- 27512128
TI - Impact of general practitioner on perceived quality of care and monitoring
maternal-newborn health outcomes in developing countries.
PMID- 27512129
TI - Implementing electronic handover: interventions to improve efficiency, safety and
sustainability.
AB - PROBLEM: Effective handovers are critical for patient care and safety. Electronic
handover tools are increasingly used today to provide an effective and
standardized platform for information exchange. The implementation of an
electronic handover system in tertiary hospitals can be a major challenge.
Previous efforts in implementing an electronic handover tool failed due to poor
compliance and buy-in from end-users. A new electronic handover tool was
developed and incorporated into the existing electronic medical records (EMRs)
for medical patients in Singapore General Hospital (SGH). INITIAL ASSESSMENT:
There was poor compliance by on-call doctors in acknowledging electronic
handovers, and lack of adherence to safety rules, raising concerns about the
safety and efficiency of the electronic handover tool. Urgent measures were
needed to ensure its safe and sustained use. SOLUTION: A quality improvement
group comprising stakeholders, including end-users, developed multi-faceted
interventions using rapid PDSA (P-Plan, D-Do, S-Study, A-Act ) cycles to address
these issues. IMPLEMENTATION: Innovative solutions using media and online
software provided cost-efficient measures to improve compliance. EVALUATION: The
percentage of unacknowledged handovers per day was used as the main outcome
measure throughout all PDSA cycles. Doctors were also assessed for improvement in
their knowledge of safety rules and their perception of the electronic handover
tool. LESSONS LEARNT: An electronic handover tool complementing daily clinical
practice can be successfully implemented using solutions devised through close
collaboration with end-users supported by the senior leadership. A combined
'bottom-up' and 'top-down' approach with regular process evaluations is crucial
for its long-term sustainability.
PMID- 27512130
TI - Improving inpatient environments to support patient sleep.
AB - PURPOSE: Although sleep is important for healing, sleep deprivation is a major
concern for patients in hospitals. The purpose of this review is to consolidate
the observational and interventional studies that have been done to understand
exogenous, non-pharmacological strategies for improving sleep in hospitals. DATA
SOURCES: We searched Medline, CINAHL, PsycINFO and the Web of Science databases
for peer-reviewed articles published between 1970 and 2015 in English. STUDY
SELECTION: A title review of 13,113 articles from four databases resulted in 783
articles that were further culled to 277 based on a review of the abstracts. The
net result after reading the articles and a hand search was 42 articles. DATA
EXTRACTION: From each article we recorded the independent variables, methods used
for measuring sleep and specific sleep outcomes reported. RESULTS OF DATA
SYNTHESIS: Noise is a modifiable cause of some sleep disruptions in hospitals,
and when reduced can lead to more sleep. Earplugs and eye masks may help, but
changing the sound and light environment is more effective. Calming music in the
evening has been shown to be effective as well as daytime bright light exposure.
Nursing care activities cause sleep disruption, but efforts at limiting
interventions have not been demonstrated to improve sleep conditions. CONCLUSION:
The research is hard to consolidate due to the multitude of independent variables
and outcome metrics, but overall points to the potential for making meaningful
improvements in the quality of patient sleep.
PMID- 27512131
TI - Evidence for ship noise impacts on humpback whale foraging behaviour.
AB - Noise from shipping activity in North Atlantic coastal waters has been steadily
increasing and is an area of growing conservation concern, as it has the
potential to disrupt the behaviour of marine organisms. This study examines the
impacts of ship noise on bottom foraging humpback whales (Megaptera novaeangliae)
in the western North Atlantic. Data were collected from 10 foraging whales using
non-invasive archival tags that simultaneously recorded underwater movements and
the acoustic environment at the whale. Using mixed models, we assess the effects
of ship noise on seven parameters of their feeding behaviours. Independent
variables included the presence or absence of ship noise and the received level
of ship noise at the whale. We found significant effects on foraging, including
slower descent rates and fewer side-roll feeding events per dive with increasing
ship noise. During 5 of 18 ship passages, dives without side-rolls were observed.
These findings indicate that humpback whales on Stellwagen Bank, an area with
chronically elevated levels of shipping traffic, significantly change foraging
activity when exposed to high levels of ship noise. This measureable reduction in
within-dive foraging effort of individual whales could potentially lead to
population-level impacts of shipping noise on baleen whale foraging success.
PMID- 27512132
TI - Seascape and life-history traits do not predict self-recruitment in a coral reef
fish.
AB - The persistence and resilience of many coral reef species are dependent on rates
of connectivity among sub-populations. However, despite increasing research
efforts, the spatial scale of larval dispersal remains unpredictable for most
marine metapopulations. Here, we assess patterns of larval dispersal in the
angelfish Centropyge bicolor in Kimbe Bay, Papua New Guinea, using parentage and
sibling reconstruction analyses based on 23 microsatellite DNA loci. We found
that, contrary to previous findings in this system, self-recruitment (SR) was
virtually absent at both the reef (0.4-0.5% at 0.15 km(2)) and the lagoon scale
(0.6-0.8% at approx. 700 km(2)). While approximately 25% of the collected
juveniles were identified as potential siblings, the majority of sibling pairs
were sampled from separate reefs. Integrating our findings with earlier research
from the same system suggests that geographical setting and life-history traits
alone are not suitable predictors of SR and that high levels of localized
recruitment are not universal in coral reef fishes.
PMID- 27512133
TI - Inferring node dates from tip dates in fossil Canidae: the importance of tree
priors.
AB - Tip-dating methods are becoming popular alternatives to traditional node
calibration approaches for building time-scaled phylogenetic trees, but questions
remain about their application to empirical datasets. We compared the performance
of the most popular methods against a dated tree of fossil Canidae derived from
previously published monographs. Using a canid morphology dataset, we performed
tip-dating using BEAST v. 2.1.3 and MrBayes v. 3.2.5. We find that for key nodes
(Canis, approx. 3.2 Ma, Caninae approx. 11.7 Ma) a non-mechanistic model using a
uniform tree prior produces estimates that are unrealistically old (27.5, 38.9
Ma). Mechanistic models (incorporating lineage birth, death and sampling rates)
estimate ages that are closely in line with prior research. We provide a
discussion of these two families of models (mechanistic versus non-mechanistic)
and their applicability to fossil datasets.
PMID- 27512134
TI - Spider silk felting-functional morphology of the ovipositor tip of Clistopyga sp.
(Ichneumonidae) reveals a novel use of the hymenopteran ovipositor.
AB - Apical serrations of the hymenopteran ovipositor have been widely postulated to
originally constitute adaptations for cutting through hard substrates.
Simplifications of the ovipositor tip have occurred in several ichneumonid wasp
genera associated with spiders. Despite such reduction in Clistopyga
(Hymenoptera, Ichneumonidae), the ovipositor still possesses some apical
serrations. Through the first detailed study, we believe, on the behaviour of an
ovipositing Clistopyga species, we show that it can alter its ovipositor for
different purposes and that the primary function of the apical serrations is
clinging to its spider host as the spider attempts to escape. Intriguingly, we
also discover a hitherto undocumented adaptation for the hymenopteran ovipositor.
The female wasp seals openings in the silken spider nest by using its ovipositor
on the silk in a highly sophisticated way that is comparable to how humans
entangle wool by needle felting. By studying the ovipositor morphology through a
scanning electron microscope, we elucidate how this works, and we hypothesize
that by closing the nest the female wasp protects its developing kin.
PMID- 27512135
TI - Intruder colour and light environment jointly determine how nesting male
stickleback respond to simulated territorial intrusions.
AB - Variation in male nuptial colour signals might be maintained by negative
frequency-dependent selection. This can occur if males are more aggressive
towards rivals with locally common colour phenotypes. To test this hypothesis, we
introduced red or melanic three-dimensional printed-model males into the
territories of nesting male stickleback from two optically distinct lakes with
different coloured residents. Red-throated models were attacked more in the
population with red males, while melanic models were attacked more in the melanic
male lake. Aggression against red versus melanic models also varied across a
depth gradient within each lake, implying that the local light environment also
modulated the strength of negative frequency dependence acting on male nuptial
colour.
PMID- 27512136
TI - Maternal condition and previous reproduction interact to affect offspring sex in
a wild mammal.
AB - Trivers and Willard proposed that offspring sex ratio should vary with maternal
condition when condition, meant as maternal capacity to care, has different
fitness consequences for sons and daughters. In polygynous and dimorphic species,
mothers in good condition should preferentially produce sons, whereas mothers in
poor condition should produce more daughters. Despite its logical appeal, support
for this hypothesis has been inconsistent. Sex-ratio variation may be influenced
by additional factors, such as environmental conditions and previous
reproduction, which are often ignored in empirical studies. We analysed 39 years
of data on bighorn sheep (Ovis canadensis) that fit all the assumptions of the
Trivers-Willard hypothesis. Production of sons increased with maternal condition
only for mothers that weaned a son the previous year. This relationship likely
reflects a mother's ability to bear the higher reproductive costs of sons. The
interaction between maternal condition and previous weaning success on the
probability of producing a son was independent of the positive effect of paternal
reproductive success. Maternal and paternal effects accounted for similar
proportions of the variance in offspring sex. Maternal reproductive history
should be considered in addition to current condition in studies of sex
allocation.
PMID- 27512137
TI - Sampling methods for exploring between-subject variability in cardiac
electrophysiology experiments.
AB - Between-subject and within-subject variability is ubiquitous in biology and
physiology, and understanding and dealing with this is one of the biggest
challenges in medicine. At the same time, it is difficult to investigate this
variability by experiments alone. A recent modelling and simulation approach,
known as population of models (POM), allows this exploration to take place by
building a mathematical model consisting of multiple parameter sets calibrated
against experimental data. However, finding such sets within a high-dimensional
parameter space of complex electrophysiological models is computationally
challenging. By placing the POM approach within a statistical framework, we
develop a novel and efficient algorithm based on sequential Monte Carlo (SMC). We
compare the SMC approach with Latin hypercube sampling (LHS), a method commonly
adopted in the literature for obtaining the POM, in terms of efficiency and
output variability in the presence of a drug block through an in-depth
investigation via the Beeler-Reuter cardiac electrophysiological model. We show
improved efficiency for SMC that produces similar responses to LHS when making
out-of-sample predictions in the presence of a simulated drug block. Finally, we
show the performance of our approach on a complex atrial electrophysiological
model, namely the Courtemanche-Ramirez-Nattel model.
PMID- 27512138
TI - Controlled cobalt doping in the spinel structure of magnetosome magnetite: new
evidences from element- and site-specific X-ray magnetic circular dichroism
analyses.
AB - The biomineralization of magnetite nanocrystals (called magnetosomes) by
magnetotactic bacteria (MTB) has attracted intense interest in biology, geology
and materials science due to the precise morphology of the particles, the chain
like assembly and their unique magnetic properties. Great efforts have been
recently made in producing transition metal-doped magnetosomes with modified
magnetic properties for a range of applications. Despite some successful
outcomes, the coordination chemistry and magnetism of such metal-doped
magnetosomes still remain largely unknown. Here, we present new evidences from X
ray magnetic circular dichroism (XMCD) for element- and site-specific magnetic
analyses that cobalt is incorporated in the spinel structure of the magnetosomes
within Magnetospirillum magneticum AMB-1 through the replacement of Fe(2+) ions
by Co(2+) ions in octahedral (Oh) sites of magnetite. Both XMCD at Fe and Co L2,3
edges, and energy-dispersive X-ray spectroscopy on transmission electron
microscopy analyses reveal a heterogeneous distribution of cobalt occurring
either in different particles or inside individual particles. Compared with non
doped one, cobalt-doped magnetosome sample has lower Verwey transition
temperature and larger magnetic coercivity, related to the amount of doped
cobalt. This study also demonstrates that the addition of trace cobalt in the
growth medium can significantly improve both the cell growth and the magnetosome
formation within M. magneticum AMB-1. Together with the cobalt occupancy within
the spinel structure of magnetosomes, this study indicates that MTB may provide a
promising biomimetic system for producing chains of metal-doped single-domain
magnetite with an appropriate tuning of the magnetic properties for technological
and biomedical applications.
PMID- 27512139
TI - Splendid coloration of the peacock spider Maratus splendens.
AB - Jumping spiders are well known for their acute vision and often bright colours.
The male peacock spider Maratus splendens is richly coloured by scales that cover
the body. The colours of the white, cream and red scales, which have an elaborate
shape with numerous spines, are pigmentary. Blue scales are unpigmented and have
a structural colour, created by an intricate photonic system consisting of two
chitinous layers with ridges, separated by an air gap, with on the inner sides of
the chitin layers an array of filaments. We have characterized the optical
properties of the scales by microspectrophotometry, imaging scatterometry and
light and scanning electron microscopy. Optical modelling revealed that the
filament array constitutes a novel structural coloration system, which subtly
fine tunes the scale reflectance to the observed blue coloration.
PMID- 27512140
TI - The telomeric protein AKTIP interacts with A- and B-type lamins and is involved
in regulation of cellular senescence.
AB - AKTIP is a shelterin-interacting protein required for replication of telomeric
DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins
and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP
localizes at the nuclear rim and in discrete regions of the nucleoplasm just like
lamins. Double immunostaining revealed that AKTIP partially co-localizes with
lamin B1 and lamin A/C in interphase cells, and that proper AKTIP localization
requires functional lamin A. In mitotic cells, AKTIP is enriched at the spindle
poles and at the midbody of late telophase cells similar to lamin B1. AKTIP
depleted cells show senescence-associated markers and recapitulate several
aspects of the progeroid phenotype. Collectively, our results indicate that AKTIP
is a new player in lamin-related processes, including those that govern nuclear
architecture, telomere homeostasis and cellular senescence.
PMID- 27512141
TI - Inhibition of Bcl-xL sensitizes cells to mitotic blockers, but not mitotic
drivers.
AB - Cell fate in response to an aberrant mitosis is governed by two competing
networks: the spindle assembly checkpoint (SAC) and the intrinsic apoptosis
pathway. The mechanistic interplay between these two networks is obscured by
functional redundancy and the ability of cells to die either in mitosis or in the
subsequent interphase. By coupling time-lapse microscopy with selective
pharmacological agents, we systematically probe pro-survival Bcl-xL in response
to various mitotic perturbations. Concentration matrices show that BH3-mimetic
mediated inhibition of Bcl-xL synergises with perturbations that induce an SAC
mediated mitotic block, including drugs that dampen microtubule dynamics, and
inhibitors targeting kinesins and kinases required for spindle assembly. By
contrast, Bcl-xL inhibition does not synergize with drugs which drive cells
through an aberrant mitosis by overriding the SAC. This differential effect,
which is explained by compensatory Mcl-1 function, provides opportunities for
patient stratification and combination treatments in the context of cancer
chemotherapy.
PMID- 27512142
TI - A drug-compatible and temperature-controlled microfluidic device for live-cell
imaging.
AB - Monitoring cellular responses to changes in growth conditions and perturbation of
targeted pathways is integral to the investigation of biological processes.
However, manipulating cells and their environment during live-cell-imaging
experiments still represents a major challenge. While the coupling of
microfluidics with microscopy has emerged as a powerful solution to this problem,
this approach remains severely underexploited. Indeed, most microdevices rely on
the polymer polydimethylsiloxane (PDMS), which strongly absorbs a variety of
molecules commonly used in cell biology. This effect of the microsystems on the
cellular environment hampers our capacity to accurately modulate the composition
of the medium and the concentration of specific compounds within the microchips,
with implications for the reliability of these experiments. To overcome this
critical issue, we developed new PDMS-free microdevices dedicated to live-cell
imaging that show no interference with small molecules. They also integrate a
module for maintaining precise sample temperature both above and below ambient as
well as for rapid temperature shifts. Importantly, changes in medium composition
and temperature can be efficiently achieved within the chips while recording cell
behaviour by microscopy. Compatible with different model systems, our platforms
provide a versatile solution for the dynamic regulation of the cellular
environment during live-cell imaging.
PMID- 27512143
TI - Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion
injury through the clearance of CLP36.
AB - Cardiovascular disease (CVD) is the leading cause of the death worldwide. An
increasing number of studies have found that autophagy is involved in the
progression or prevention of CVD. However, the precise mechanism of autophagy in
CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is
unclear and controversial. Here, we show that the cardiomyocyte-specific
disruption of autophagy by conditional knockout of Atg7 leads to severe
contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A
negative cytoskeleton organization regulator, CLP36, was found to be accumulated
in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7
aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction,
myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36
accumulation in cardiomyocytes. Altogether, this work reveals autophagy may
protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and
these findings define a novel relationship between autophagy and the regulation
of stress fibre in heart.
PMID- 27512144
TI - Continental cichlid radiations: functional diversity reveals the role of changing
ecological opportunity in the Neotropics.
AB - Adaptive radiations have been hypothesized to contribute broadly to the diversity
of organisms. Models of adaptive radiation predict that ecological opportunity
and ecological release, the availability of empty ecological niches and the
response by adapting lineages to occupy them, respectively, drive patterns of
phenotypic and lineage diversification. Adaptive radiations driven by 'ecological
opportunity' are well established in island systems; it is less clear if
ecological opportunity influences continent-wide diversification. We use
Neotropical cichlid fishes to test if variation in rates of functional evolution
is consistent with changing ecological opportunity. Across a functional
morphological axis associated with ram-suction feeding traits, evolutionary rates
declined through time as lineages diversified in South America. Evolutionary
rates of ram-suction functional morphology also appear to have accelerated as
cichlids colonized Central America and encountered renewed opportunity. Our
results suggest that ecological opportunity may play an important role in shaping
patterns of morphological diversity of even broadly distributed lineages like
Neotropical cichlids.
PMID- 27512145
TI - Parasites contribute to ecologically dependent postmating isolation in the
adaptive radiation of three-spined stickleback.
AB - Spatial variation in parasitic infections is common, and has the potential to
drive population divergence and the reproductive isolation of hosts. However,
despite support from theory and model laboratory systems, little strong evidence
has been forthcoming from the wild. Here, we show that parasites are likely to
cause reproductive isolation in the adaptive radiation of three-spined
stickleback. Adjacent wild populations on the Scottish island of North Uist
differ greatly and consistently in the occurrence of different parasites that
have substantial effects on fitness. Laboratory-reared fish are more resistant to
experimental infection by parasite species from their own population.
Furthermore, hybrid backcrosses between the host populations are more resistant
to parasites from the parental population to which they are more closely related.
These patterns provide strong evidence that parasites can cause ecological
speciation, by contributing to selection against migrants and ecologically
dependent postmating isolation.
PMID- 27512146
TI - Evidence for water-mediated mechanisms in coral-algal interactions.
AB - Although many coral reefs have shifted from coral-to-algal dominance, the
consequence of such a transition for coral-algal interactions and their
underlying mechanisms remain poorly understood. At the microscale, it is unclear
how diffusive boundary layers (DBLs) and surface oxygen concentrations at the
coral-algal interface vary with algal competitors and competitiveness. Using
field observations and microsensor measurements in a flow chamber, we show that
coral (massive Porites) interfaces with thick turf algae, macroalgae, and
cyanobacteria, which are successful competitors against coral in the field, are
characterized by a thick DBL and hypoxia at night. In contrast, coral interfaces
with crustose coralline algae, conspecifics, and thin turf algae, which are
poorer competitors, have a thin DBL and low hypoxia at night. Furthermore, DBL
thickness and hypoxia at the interface with turf decreased with increasing flow
speed, but not when thick turf was upstream. Our results support the importance
of water-mediated transport mechanisms in coral-algal interactions. Shifts
towards algal dominance, particularly dense assemblages, may lead to thicker
DBLs, higher hypoxia, and higher concentrations of harmful metabolites and
pathogens along coral borders, which in turn may facilitate algal overgrowth of
live corals. These effects may be mediated by flow speed and orientation.
PMID- 27512147
TI - Host stress hormones alter vector feeding preferences, success, and productivity.
AB - Stress hormones might represent a key link between individual-level infection
outcome, population-level parasite transmission, and zoonotic disease risk.
Although the effects of stress on immunity are well known, stress hormones could
also affect host-vector interactions via modification of host behaviours or
vector-feeding patterns and subsequent reproductive success. Here, we
experimentally manipulated songbird stress hormones and examined subsequent
feeding preferences, feeding success, and productivity of mosquito vectors in
addition to defensive behaviours of hosts. Despite being more defensive, birds
with elevated stress hormone concentrations were approximately twice as likely to
be fed on by mosquitoes compared to control birds. Moreover, stress hormones
altered the relationship between the timing of laying and clutch size in blood
fed mosquitoes. Our results suggest that host stress could affect the
transmission dynamics of vector-borne parasites via multiple pathways.
PMID- 27512148
TI - Dead ant walking: a myrmecophilous beetle predator uses parasitoid host location
cues to selectively prey on parasitized ants.
AB - Myrmecophiles (i.e. organisms that associate with ants) use a variety of
ecological niches and employ different strategies to survive encounters with
ants. Because ants are typically excellent defenders, myrmecophiles may choose
moments of weakness to take advantage of their ant associates. This hypothesis
was studied in the rove beetle, Myrmedonota xipe, which associates with Azteca
sericeasur ants in the presence of parasitoid flies. A combination of laboratory
and field experiments show that M. xipe beetles selectively locate and prey upon
parasitized ants. These parasitized ants are less aggressive towards beetles than
healthy ants, allowing beetles to eat the parasitized ants alive without
interruption. Moreover, behavioural assays and chemical analysis reveal that M.
xipe are attracted to the ant's alarm pheromone, the same secretion used by the
phorid fly parasitoids in host location. This strategy allows beetles access to
an abundant but otherwise inaccessible resource, as A. sericeasur ants are
typically highly aggressive. These results are the first, to our knowledge, to
demonstrate a predator sharing cues with a parasitoid to gain access to an
otherwise unavailable prey item. Furthermore, this work highlights the importance
of studying ant-myrmecophile interactions beyond just their pairwise context.
PMID- 27512149
TI - Uterotonic Neuromedin U Receptor 2 and Its Ligands Are Upregulated by
Inflammation in Mice and Humans, and Elicit Preterm Birth.
AB - Uterine labor requires the conversion of a quiescent (propregnancy) uterus into
an activated (prolabor) uterus, with increased sensitivity to endogenous
uterotonic molecules. This activation is induced by stressors, particularly
inflammation in term and preterm labor. Neuromedin U (NmU) is a neuropeptide
known for its uterocontractile effects in rodents. The objective of the study was
to assess the expression and function of neuromedin U receptor 2 (NmU-R2) and its
ligands NmU and the more potent neuromedin S (NmS) in gestational tissues, and
the possible implication of inflammatory stressors in triggering this system. Our
data show that NmU and NmS are uterotonic ex vivo in murine tissue, and they dose
dependently trigger labor by acting specifically via NmU-R2. Expression of NmU
R2, NmU, and NmS is detected in murine and human gestational tissues by
immunoblot, and the expression of NmS in placenta and of NmU-R2 in uterus
increases considerably with gestation age and labor, which is associated with
amplified NmU-induced uterocontractile response in mice. NmU- and NmS-induced
contraction is associated with increased NmU-R2-coupled Ca++ transients, and Akt
and Erk activation in murine primary myometrial smooth muscle cells (mSMCs),
which are potentiated with gestational age. NmU-R2 is upregulated in vitro in
mSMCs and in vivo in uterus in response to proinflammatory interleukin 1beta
(IL1beta), which is associated with increased NmU-induced uterocontractile
response and Ca++ transients in murine and human mSMCs; additionally, placental
NmS is markedly upregulated in vivo in response to IL1beta. In human placenta at
term, immunohistological analysis revealed NmS expression primarily in
cytotrophoblasts; furthermore, stimulation with lipopolysaccharide (LPS; Gram
negative endotoxin) markedly upregulates NmS expression in primary human
cytotrophoblasts isolated from term placentas. Correspondingly, decidua of women
with clinical signs of infection who delivered preterm display significantly
higher expression of NmS compared with those without infection. Importantly, in
vivo knockdown of NmU-R2 prevents LPS-triggered preterm birth in mice and the
associated neonatal mortality. Altogether, our data suggest a critical role for
NmU-R2 and its ligands NmU and NmS in preterm labor triggered by infection. We
hereby identify NmU-R2 as a relevant target for preterm birth.
PMID- 27512150
TI - EPHB4 Regulates Human Trophoblast Cell Line HTR-8/SVneo Function: Implications
for the Role of EPHB4 in Preeclampsia.
AB - Successful pregnancy depends on well-regulated extravillous trophoblast (EVT)
invasion into the uterine decidua and moderate uterine spiral artery remodeling.
Ephrin receptor B4 (EPHB4) is a membrane-anchored receptor tyrosine kinase that
plays an important role in various cellular functions in human normal tissue and
tumors. Reportedly, EPHB4 plays important roles during placentation. Still, there
is no investigation of EPHB4 modulating trophoblast function. In our study, term
placentas of preeclamptic pregnancies showed a significantly increased EPHB4
expression compared to those of uncomplicated pregnancies (n = 15). Exogenous up
regulation of EPHB4 in HTR-8/SVneo cells was performed to investigate the effects
of EPHB4 on cell biological behavior. The results showed that EPHB4 enhancement
reduced cell proliferation and promoted trophoblast apoptosis; and inhibited cell
migration, invasion, and endothelial replacement. Associated factors, such as
matrix metalloproteinases, vascular endothelial growth factor, placental growth
factor, and soluble Fms-like tyrosine kinase 1 were examined at transcriptional
level. Furthermore, cell functional results were confirmed in a placenta-decidua
coculture system, showing poor vascular remodeling. Additionally, we detected
possible down-stream PI3K-Akt signal pathway involved in EPHB4-mediated function
of HTR-8/SVneo cells. Our study demonstrates that EPHB4 overexpression may
contribute to trophoblasts dysfunction and impair maternal artery remodeling, as
is associated with the pathogenesis of preeclampsia.
PMID- 27512151
TI - Involvement of Protein Acyltransferase ZDHHC3 in Maintaining Oocyte Meiotic
Arrest in Xenopus laevis.
AB - Fully grown oocytes of most vertebrates are arrested at prophase I of meiosis (G2
arrest). Upon exposure to steroid hormones, oocytes resume meiotic process, also
called G2/M transition. The G protein-signaling pathway has been shown to play
essential roles in the meiotic arrest at G2 phase. Previously, we showed that
long chain fatty acyl-coenzyme A synthetase acsl1b was required for maintaining
the meiotic arrest in Xenopus Acsl1b presumably synthesizes palmitoyl-coenzyme A
that can be utilized by acyltransferases to modify proteins essential for the G2
arrest. In the present study, we report that protein acyltransferase ZDHHC3
functions downstream of acsl1b to maintain oocyte meiotic arrest. Depletion of
maternal ZDHHC3 RNA in oocytes reduces the progesterone threshold to promote G2/M
transition from 2 to 0.01 MUM. As expected, Gs alpha palmitoylation level is
greatly decreased in ZDHHC3-depleted oocytes. Furthermore, we mapped ZDHHC3
palmitoylation sites in Gs alpha and showed that palmitoylation-deficient Gs
alpha failed to arrest oocytes at G2. We also identified a critical residue in
ZDHHC3 critically required for its palmitoylation activity toward Gs alpha. Taken
together, ZDHHC3 is a key acyltransferase to palmitoylate proteins in order to
maintain G2 arrest in Xenopus oocytes.
PMID- 27512152
TI - Uterine Histotroph and Conceptus Development. II. Arginine and Secreted
Phosphoprotein 1 Cooperatively Stimulate Migration and Adhesion of Ovine
Trophectoderm Cells via Focal Adhesion-MTORC2 Mediated Cytoskeleton
Reorganization.
AB - In all mammalian species, critical events, including uterine receptivity and
development of the conceptus (embryo/fetus and its associated extraembryonic
membranes), must be intricately orchestrated and carefully timed during the
window of implantation. Otherwise, failure of conceptuses to implant is
inevitable, which accounts for 50%-75% of failures to establish pregnancy. Unlike
human and rodent blastocysts, the blastocysts of pigs and ruminants undergo rapid
transitions from spherical to tubular and filamentous conceptuses in response to
histotroph during the peri-implantation period of pregnancy. Both arginine and
secreted phosphoprotein 1 (SPP1; also known as osteopontin) are multifunctional
molecules that increase significantly in ovine uterine histotroph during early
pregnancy; however, little is known about their relationship and synergistic
effects on conceptus development. Therefore, we conducted in vitro experiments
using our established ovine trophectoderm cell line (oTr1) isolated from Day 15
ovine conceptuses to determine their migratory and adhesive responses to
individual and combined effects of arginine and recombinant SPP1 (rSPP1) that
contains an Arg-Gly-Asp (RGD) binding sequence. Migration and adhesion of oTr1
cells were significantly stimulated by rSPP1, whereas arginine alone only induced
a significant increase in cell migration. However, the combination of arginine
and rSPP1 had an additive effect on migration, and a synergistic effect on
adhesion of oTr1 cells. Those cooperative effects of arginine and SPP1 were
mediated by focal adhesion assembly-MTORC2-cytoskeletal reorganization and MAPK
pathways. Collectively, results suggest that arginine and SPP1 in histotroph
affect cellular events required for rapid elongation of ovine conceptuses during
the peri-implantation period of pregnancy.
PMID- 27512153
TI - Estrogenic Compounds Impair Primordial Follicle Formation by Inhibiting the
Expression of Proapoptotic Hrk in Neonatal Rat Ovary.
AB - Exposure to endocrine-disrupting chemicals (EDCs) during fetal and neonatal
periods can have toxic effects that are irreversible and last a lifetime.
However, the mechanism underlying this phenomenon is still unknown. Here, we show
the effect of 17alpha-ethynyl estradiol (EE) on the development of the primordial
follicle during early ovarian development in female rats. Microarray analysis
revealed the down-regulation of Hrk, an activator of apoptosis, in neonatal
ovaries exposed to EE. Real-time PCR analysis also showed a decrease of Hrk mRNA
expression in ovaries treated with EE both in vitro and in neonatal rats. An
immunostaining assay showed that HRK protein and cleaved caspase 3 colocalize in
the oocytes at Postnatal Day 1 (PND1). The EE-exposed ovaries had a reduced
number of oocytes positive for TUNEL staining compared to control ovaries at
PND1. Abnormal follicle formation of EE-exposed ovaries was observed at PND7 and
PND21. A TUNEL staining assay revealed that Hrk depletion reduced the number of
apoptotic oocytes. In addition, down-regulation of Hrk mRNA expression was
observed in ovaries treated with other estrogenic chemicals. We propose a model
in which EE inhibits oocyte apoptosis in the neonatal ovary by suppressing the
expression of Hrk, thereby disrupting follicle formation and ovary function.
PMID- 27512154
TI - Changes in Myeloid Lineage Cells in the Uterus and Peripheral Blood of Dairy
Heifers During Early Pregnancy.
AB - Establishment of pregnancy requires interaction between the developing conceptus
and the uterine mucosal immune system. Myeloid lineage cells (macrophages and
dendritic cells) are key mediators of pregnancy in rodents and humans but
relatively little is known regarding their role and distribution during early
pregnancy in ruminants. We tested the hypothesis that myeloid lineage cell
number, distribution, and function are altered during early pregnancy in dairy
heifers. Dairy heifers were inseminated using sperm from a single bull (Day 0),
and uteri and blood were collected at slaughter on Days 17 and 20 of pregnancy to
investigate the response of myeloid lineage cells to the presence of a conceptus.
Responses were compared to noninseminated heifers on Day 17 of the estrous cycle.
Peripheral blood and uterine-derived immune cells were isolated magnetically and
examined using flow cytometry. Immunohistochemical analysis was used to evaluate
the spatial distribution of myeloid lineage cells in the endometrium and
quantitative polymerase chain reaction was conducted to quantify abundance of
mRNA transcripts associated with myeloid lineage cell function. Transcripts for
major histocompatibility complex (MHC) II, cluster of differentiation (CD) 80,
CD86, CD163, and indoleamine 2,3-dioxygenase (IDO) 1 were greater in endometrium
of pregnant compared to cyclic heifers. Immunofluorescence analysis revealed
increased labeling for MHCII and SIRPA in pregnant compared to cyclic heifers.
There were approximately 50% more CD14+CD11c+ cells in the peripheral circulation
of pregnant compared to cyclic heifers. A greater number of myeloid lineage cells
were observed during early pregnancy, and this increase was most pronounced in
and around the shallow glands. Furthermore, expression of molecules associated
with a tolerogenic or alternatively activated phenotype of these cells also
increased in pregnant heifers. The results support the hypothesis that myeloid
lineage cells with a tolerogenic phenotype are involved in establishment of
pregnancy in dairy heifers.
PMID- 27512155
TI - Transplacental transfer of essential thrombocythemia in monozygotic twins.
PMID- 27512156
TI - Total Radiosynthesis: Thinking outside "the box".
AB - The logic of total synthesis transformed a stagnant state of medicinal and
synthetic organic chemistry when there was a paucity of methods and reagents to
synthesize drug molecules and/or natural products. Molecular imaging by positron
emission tomography (PET) is now experiencing a renaissance in the way
radiopharmaceuticals for molecular imaging are synthesized, however, a paradigm
shift is desperately needed in the discovery pipeline to accelerate in vivo
imaging studies. A significant challenge in radiochemistry is the limited choice
of labeled reagents (or building blocks) available for the synthesis of novel
radiopharmaceuticals with the most commonly used short-lived radionuclides carbon
11 (11C; half-life ~20 minutes) and fluorine-18 (18F; half-life ~2 hours). In
fact, most drugs cannot be labeled with 11C or 18F due to a lack of efficient and
diverse radiosynthetic methods. In general, routine radiopharmaceutical
production relies on the incorporation of the isotope at the last or penultimate
step of synthesis, ideally within one half-life of the radionuclide, to maximize
radiochemical yields and specific activities thereby reducing losses due to
radioactive decay. Reliance on radiochemistry conducted within the constraints of
an automated synthesis unit ("box") has stifled the exploration of multi-step
reactions with short-lived radionuclides. Radiopharmaceutical synthesis can be
transformed by considering logic of total synthesis to develop novel approaches
for 11C- and 18F-radiolabeling complex molecules via retrosynthetic analysis and
multi-step reactions. As a result of such exploration, new methods, reagents and
radiopharmaceuticals for in vivo imaging studies are discovered. A new avenue to
develop radiotracers that were previously unattainable due to the lack of
efficient radiosynthetic methods is necessary to work towards our ultimate,
albeit impossible goal - the concept we term total radiosynthesis - to radiolabel
virtually any molecule. As with the vast majority of drugs, most radiotracers
also fail, therefore expeditious evaluation of tracers in preclinical models
prior to optimization or derivatization of the lead molecules/drugs is necessary.
Furthermore the exact position of the 11C and 18F radionuclide in tracers is
often critical for metabolic considerations, and flexible methodologies to
introduce the radiolabel are needed. Using the principles of total synthesis our
laboratory and others have shown that multi-step radiochemical reactions are
indeed suitable for preclinical and even clinical use. As the goal of total
synthesis is to be concise, we have also simplified the syntheses of
radiopharmaceuticals. We are presently developing new strategies via [11C]CO2
fixation which has enabled library radiosynthesis as well as labeling non
activated arenes using [18F]fluoride via iodonium ylides. Both of which have
proven to be suitable for human PET imaging. We concurrently utilize state-of-the
art automation technologies including microfluidic flow chemistry and rapid
purification strategies for radiopharmaceutical production. In this account we
highlight how total radiosynthesis has impacted our radiochemistry program, with
prominent examples from others, focusing on its impact towards preclinical and
clinical research studies.
PMID- 27512157
TI - Comparison of the Multiple Reaction Monitoring and Enhanced Product Ion Scan
Modes for Confirmation of Stilbenes in Bovine Urine Samples Using LC-MS/MS
QTRAP(r) System.
AB - In accordance with Commission Decision 2002/657/EC, confirmatory methods for the
detection of prohibited substances should comply with specific requirements,
including the criteria for confirmation. Two strategies: multiple reaction
monitoring (MRM) and enhanced product ion (EPI) scanning functions were compared
for confirming the anabolic compounds from synthetic stilbenes group in bovine
urine samples. In the research, twenty samples fortified at the Recommended
Concentration (RC) of 1 ug L-1 with diethylstilbestrol, dienestrol and hexestrol
were analyzed by liquid chromatography-tandem mass spectrometry on a QTRAP 5500
instrument. The analytical procedure, validated in accordance with the Commission
Decision 2002/657/EC, used in the official control of hormones in Poland was
applied. The validation parameters were in agreement with 2002/657/EC performance
criteria. The effectiveness of MRM and EPI scanning modes for confirmation
purposes was evaluated based on the percentage of the results confirmed. In all
urine samples recorded in the MRM mode, the confirmation criteria (retention
time, relative intensities between transitions) have been fulfilled. The presence
of stilbenes in all urine samples using EPI scan mode was confirmed too as
evidenced by a good matching of stilbenes spectra in the samples to the reference
spectra with critical match factor above 0.7. The results of the research show
that EPI scanning function provides the same effectiveness for confirmation of
banned compounds as the mostly used MRM scan mode and can be an additional tool
to confirm the doubtful case results in the analysis of hormones residues, even
at such low concentration levels.
PMID- 27512158
TI - Transporting critically Ill patients: Look before you leap!
PMID- 27512160
TI - Comparative assessment of ProSealTM laryngeal mask airway intervention versus
standard technique of endotracheal extubation for attenuation of pressor response
in controlled hypertensive patients.
AB - BACKGROUND AND AIMS: Swapping of the endotracheal tube with laryngeal mask airway
(LMA) before emergence from anaesthesia is one of the methods employed for
attenuation of pressor response at extubation. We decided to compare the
placement of ProSealTM LMA (PLMA) before endotracheal extubation versus
conventional endotracheal extubation in controlled hypertensive patients
scheduled for elective surgeries under general anaesthesia. METHODS: Sixty
consenting adult patients were randomly allocated to two groups of thirty each;
Group E in whom extubation was performed using standard technique and Group P in
whom PLMA was inserted before endotracheal extubation (Bailey manoeuvre). The
primary outcome parameter was heart rate (HR). The secondary outcomes were
systolic, diastolic and mean blood pressure (MBP), electrocardiogram, oxygen
saturation and end-tidal carbon dioxide. Two-tailed paired Student's t-test was
used for comparison between the two study groups. The value of P < 0.05 was
considered as statistically significant. RESULTS: The patient characteristics,
demographic data and surgical procedures were comparable in the two groups. A
statistically significant decrease was observed in HR in Group P as compared to
Group E. Secondary outcomes such as systolic, diastolic and MBP depicted a
statistically insignificant difference. CONCLUSION: Bailey manoeuvre was not
effective method to be completely relied upon during extubation when compared to
standard extubation.
PMID- 27512159
TI - Inter-hospital and intra-hospital patient transfer: Recent concepts.
AB - The intra- and inter-hospital patient transfer is an important aspect of patient
care which is often undertaken to improve upon the existing management of the
patient. It may involve transfer of patient within the same facility for any
diagnostic procedure or transfer to another facility with more advanced care. The
main aim in all such transfers is maintaining the continuity of medical care. As
the transfer of sick patient may induce various physiological alterations which
may adversely affect the prognosis of the patient, it should be initiated
systematically and according to the evidence-based guidelines. The key elements
of safe transfer involve decision to transfer and communication, pre-transfer
stabilisation and preparation, choosing the appropriate mode of transfer, i.e.,
land transport or air transport, personnel accompanying the patient, equipment
and monitoring required during the transfer, and finally, the documentation and
handover of the patient at the receiving facility. These key elements should be
followed in each transfer to prevent any adverse events which may severely affect
the patient prognosis. The existing international guidelines are evidence based
from various professional bodies in developed countries. However, in developing
countries like India, with limited infrastructure, these guidelines can be
modified accordingly. The most important aspect is implementation of these
guidelines in Indian scenario with periodical quality assessments to improve the
standard of care.
PMID- 27512161
TI - Post-operative hypertension, a surrogate marker of the graft function and
predictor of survival in living donor liver transplant recipients: A
retrospective study.
AB - BACKGROUND AND AIMS: De novo hypertension (HTN) in liver transplantation
recipients is a known entity. We investigated haemodynamic behaviour after a
liver transplant to see if it can predict survival to discharge from the
hospital. METHODS: electronic records of Haemodynamic parameters and laboratory
investigations of 95 patients of living donor liver transplant (LDLT) were
retrospectively analysed. RESULTS: Twenty-three patients were operated for acute
liver failure (ALF) and 72 patients for chronic liver disease (CLD). Eight
patients of CLD and four of ALF did not survive. CLD patients had statistically
significant rise in systolic blood pressure from the post-operative day (POD) 1
to POD 4 and diastolic blood pressure (DBP) from POD 3 to POD 6. Heart rate (HR)
significantly decreased from POD 3 to POD 5. Haemodynamic parameters returned to
baseline values within 20 days. Diastolic HTN had a positive predictive value of
100% for survival with 100% sensitivity and specificity. Systolic HTN had a
positive predictive value of 100% for survival (sensitivity-89%, specificity
100%). ALF patients had a significant decrease in HR from POD 2 to POD 10.
Bradycardia (HR <=60/min) had a positive predictive value of 100% for survival
with a sensitivity of 45% and 58% in CLD and ALF, respectively, with a
specificity of 100% in both the groups. Non-survivors had no significant change
in haemodynamics. In CLD group, International Normalised Ratio had statistically
significant, strong negative correlation with DBP. CONCLUSION: Haemodynamic
pattern of recovery may be used for predicting survival to discharge after LDLT.
PMID- 27512162
TI - A comparative study of two techniques (electrocardiogram- and landmark-guided)
for correct depth of the central venous catheter placement in paediatric patients
undergoing elective cardiovascular surgery.
AB - BACKGROUND AND AIMS: The complications of central venous catheterisation can be
minimized by ensuring catheter tip placement just above the superior vena cava
right atrium junction. We aimed to compare two methods, using an
electrocardiogram (ECG) or landmark as guides, for assessing correct depth of
central venous catheter (CVC) placement. METHODS: In a prospective randomised
study of sixty patients of <12 years of age, thirty patients each were allotted
randomly to two groups (ECG and landmark). After induction, central venous
catheterisation was performed by either of the two techniques and position of CVC
tip was compared in post-operative chest X-ray with respect to carina. Unpaired t
test was used for quantitative data and Chi-square test was used for qualitative
data. RESULTS: In ECG group, positions of CVC tip were above carina in 12, at
carina in 9 and below carina in 9 patients. In landmark group, the positions of
CVC tips were above carina in 10, at carina in 4 and below carina in 16 patients.
Mean distance of CVC tip in ECG group was 0.34 +/- 0.23 cm and 0.66 +/- 0.35 cm
in landmark group (P = 0.0001). Complications occurred in one patient in ECG
group and in nine patients in landmark group (P = 0.0056). CONCLUSION: Overall,
landmark-guided technique was comparable with ECG technique. ECG-guided technique
was more precise for CVC tip placement closer to carina. The incidence of
complications was more in the landmark group.
PMID- 27512163
TI - Anaesthesia and intensive care for simultaneous liver-kidney transplantation: A
single-centre experience with 12 recipients.
AB - BACKGROUND AND AIMS: The perioperative management of patients presenting for
simultaneous liver and kidney transplantation (SLKT) is a complex process. We
analysed SLKTs performed in our institution to identify preoperative,
intraoperative and post-operative challenges encountered in the management.
METHODS: We retrospectively studied the case records of 12 patients who underwent
SLKT between 2009 and 2014 and analysed details of pre-operative evaluation and
optimisation, intraoperative anaesthetic management and the implications of use
of perioperative continuous renal replacement therapy (CRRT) and the post
operative course of these patients. RESULTS: Of the total 12 cases, 4 were under
16 years of age. The indications for SLKT were primary hyperoxaluria (5),
congenital hepatic fibrosis with polycystic kidney disease (2), ethanol-related
end-stage liver disease (ESLD) with hepatorenal syndrome type 1 (1). Four
patients had ESLD with end-stage renal disease due to other causes. Six
recipients received live donor grafts and 6 patients received cadaveric grafts.
Seven patients received intraoperative CRRT. Mean duration of surgery was 12.5 h.
Cardiac output monitors used were trans-oesophageal echocardiogram (2), pulmonary
artery catheter (1) and pulse contour cardiac output monitor (3). There was 1
sepsis-related mortality on 7(th) post-operative day. CONCLUSION: A thorough pre
operative evaluation and optimisation, knowledge and anticipation of potential
problems, and meticulous intraoperative fluid management guided by appropriate
monitoring and use of CRRT when needed can help in achieving successful outcomes.
PMID- 27512164
TI - Ultrasound-guided femoro-sciatic nerve block for post-operative analgesia after
below knee orthopaedic surgeries under subarachnoid block: Comparison between
clonidine and dexmedetomidine as adjuvants to levobupivacaine.
AB - BACKGROUND AND AIMS: The advent of ultrasonographic-guided techniques has led to
increased interest in femoro-sciatic nerve block (FSNB) for lower limb surgeries.
alpha2-agonists have been used recently as adjuvants to local anaesthetics in
nerve blocks. We aimed to compare equal doses of clonidine or dexmedetomidine as
an adjuvant to levobupivacaine in FSNB for post-operative analgesia. METHODS:
Ninety patients scheduled to undergo below knee orthopaedic surgeries under
subarachnoid block were divided into three groups: Group LL (n = 30) patients
received 38 mL of 0.125% levobupivacaine with 2 mL normal saline, Group LD (n =
30) patients received 38 mL of 0.125% levobupivacaine with 0.5 MUg/kg
dexmedetomidine and Group LC (n = 30) received 38 mL of 0.125% levobupivacaine
with 0.5 MUg/kg clonidine in saline to make total drug volume of 40 mL. The
primary and secondary outcome variables were duration of analgesia and rescue
analgesic requirement, verbal rating score respectively. Continuous variables
were analysed with analysis of variance or the Kruskal-Wallis test on the basis
of data distribution. Categorical variables were analysed with the contingency
table analysis and the Fisher's exact test. RESULTS: Duration of analgesia was
prolonged with dexmedetomidine (10.17 +/- 2.40 h) and clonidine (7.31 +/- 1.76 h)
as compared to control (4.16 +/- 1.04 h, P = 0.00). Significantly lower pain
scores were observed in dexmedetomidine group as compared to clonidine up to 8 h
post-operatively. CONCLUSION: Equal doses of clonidine or dexmedetomidine added
to levobupivacaine prolonged the duration of analgesia, decreased requirement of
rescue analgesia. Dexmedetomidine delays the requirement of rescue analgesics
with better pain scores as compared to clonidine.
PMID- 27512166
TI - A comparative study of landmark-based topographic method versus the formula
method for estimating depth of insertion of right subclavian central venous
catheters.
AB - BACKGROUND AND AIMS: Subclavian central venous catheterisation (CVC) is employed
in critically ill patients requiring long-term central venous access. There is no
gold standard for estimating their depth of insertion. In this study, we compared
the landmark topographic method with the formula technique for estimating depth
of insertion of right subclavian CVCs. METHODS: Two hundred and sixty patients
admitted to Intensive Care Unit requiring subclavian CVC were randomly assigned
to either topographic method or formula method (130 in each group). Catheter tip
position in relation to the carina was measured on a post-procedure chest X-ray.
The primary endpoint was the need for catheter repositioning. Mann-Whitney test
and Chi-square test was performed for statistical analysis using SPSS for windows
version 18.0 (Armonk, NY: IBM Corp). RESULTS: Nearly, half the catheters
positioned by both the methods were situated >1 cm below the carina and required
repositioning. CONCLUSION: Both the techniques were not effective in estimating
the approximate depth of insertion of right subclavian CVCs.
PMID- 27512165
TI - Efficacy of magnesium as an adjuvant to bupivacaine in 3-in-1 nerve block for
arthroscopic anterior cruciate ligament repair.
AB - BACKGROUND AND AIMS: Three-in-one and femoral nerve blocks are proven modalities
for postoperative analgesia following anterior cruciate ligament (ACL)
reconstruction. The aim of this study was to evaluate the efficacy of magnesium
(Mg) as an adjuvant to bupivacaine in 3-in-1 block for ACL reconstruction.
METHODS: Sixty patients undergoing arthroscopic ACL reconstruction were randomly
allocated to Group I (3-in-1 block with 30 ml of 0.25% bupivacaine preceded by
1.5 ml of intravenous [IV] saline), Group II (3-in-1 block with 30 ml of 0.25%
bupivacaine preceded by 1.5 ml of solution containing 150 mg Mg IV) or Group III
(3-in-1 block with 30 ml containing 0.25% bupivacaine and 150 mg of Mg as
adjuvant preceded by 1.5 ml of IV saline). Post-operatively, patients received
morphine when visual analogue scale (VAS) score was >=4. Quantitative parameters
were compared using one-way ANOVA and Kruskal-Wallis test and qualitative data
were analysed using Chi-square test. RESULTS: Demographics, haemodynamic
parameters, intra-operative fentanyl requirement, post-operative VAS scores and
total morphine requirement were comparable between groups. Time to first
analgesic requirement was significantly prolonged in Group III (789 +/- 436) min
compared to Group I (466 +/- 290 min) and Group II (519 +/- 274 min), (P = 0.02
and 0.05). Significantly less number of patients in Group III (1/20) received
morphine in the first 6 h post-operatively, compared to Group I (8/20) and Group
II (6/20) (P = 0.008 and 0.03). No side effects were observed. CONCLUSION: Mg as
an adjuvant to bupivacaine in 3-in-1 block for ACL reconstruction significantly
prolongs the time to first analgesic requirement and reduces the number of
patients requiring morphine in the immediate post-operative period.
PMID- 27512167
TI - The comparative evaluation of safety and efficacy of unilateral paravertebral
block with conventional spinal anaesthesia for inguinal hernia repair.
AB - BACKGROUND AND AIMS: Unilateral paravertebral block (PVB) as a sole anaesthetic
technique is underutilised even in experienced hands. Hence, this study was
undertaken regarding the efficacy and safety of PVB and compared with
subarachnoid block (SAB) for inguinal hernia repair procedures. METHODS: Sixty
three consenting adult male patients scheduled for unilateral inguinal hernia
repair were randomly assigned to receive either PVB or SAB (Group P: PVBs at T10
L2 levels, 5 mL of 0.5% bupivacaine at each segment; Group S: SAB at L3-L4 level
with 12.5 mg 0.5% of hyperbaric bupivacaine). Primary objective was to compare
duration of post-operative analgesia and time to reach discharge criteria
(modified Aldrete scores and modified post-anaesthetic discharge scoring [PADS]
scores). Secondary objectives were to compare the block characteristics (time
required for performing the block, time to surgical anaesthesia, time to
ambulation, time to the first analgesic, total rescue analgesic consumption) and
adverse effects. Independent Student's t-test was used for continuous data and
Pearson Chi-square test for categorical data. P <0.05 was considered as
statistically significant. RESULTS: The duration of post-operative analgesia
(min) was 384.57 +/- 38.67 in Group P and 194.27 +/- 20.30 in Group S (P < 0.05).
Modified PADS scores were significantly higher at 4 h and 6 h (P < 0.0001) in
Group P. Time to reach the discharge criteria was early in Group P than Group S.
CONCLUSION: PVB provides excellent post-operative analgesic conditions with
lesser adverse effects and shorter time to reach the discharge criteria compared
to SAB.
PMID- 27512168
TI - Failed fibreoptic intubation: 70 degrees rigid nasendoscope and Frova introducer
to the rescue.
AB - Endotracheal intubation was successfully accomplished with 70 degrees rigid
nasendoscope under video guidance in two patients in whom repeated attempts to
secure airway with flexible fibreoptic bronchoscope were unsuccessful. Both
patients had compromised airway (laryngeal papillomatosis and a huge thyroid
swelling) and were uncooperative. Frova intubating introducer was used along with
70 degrees rigid nasendoscope to accomplish tracheal intubation under video
guidance.
PMID- 27512169
TI - A novel method of airway management in a case of penetrating neck injury.
AB - Direct injury to airway is a rare event and also a challenge to anaesthesiologist
and surgeon. We present a case report of open tracheal injury with right
pneumothorax in a young male following assault with a sharp weapon. In spite of a
chest tube in situ, the patient came with collapse of one lung and tachypnoea
which required surgical exploration. Lower airway was evaluated by fibre-optic
bronchoscopy through the open tracheal wound while he was awake and tracheal tube
was passed over the bronchoscope. There was no vascular or oesophageal injury
detected. Although there was a pleural tear, there were no signs of injury to
lung parenchyma. After evaluation, end to end anastomosis of the trachea was
planned, for which orotracheal tube was passed with surgical assistance. Patient
was shifted to post-operative high dependency unit and was electively ventilated
for 7 days and was later successfully extubated under fibre-optic bronchoscope
guidance.
PMID- 27512170
TI - A low cost, customised anaesthesia information management system: An evolving
process.
PMID- 27512171
TI - Intraoperative hyperthermia: Can surgery itself be a cause?
PMID- 27512172
TI - Anaesthetic concerns of a pregnant patient with Pott's spine for spine surgery in
prone position.
PMID- 27512173
TI - Intra-hospital transfer: Human error and safety concerns with improper setting up
of a cylinder-based oxygen delivery system.
PMID- 27512174
TI - A novel technique for securing supra-glottic airway device to prevent mal
positioning.
PMID- 27512175
TI - Intraoperative air embolism during hepatectomy.
PMID- 27512176
TI - Difficult epidural in a patient with undiagnosed alkaptonuria.
PMID- 27512177
TI - Spinal needle with prefilled syringe to prevent medication error: A proposal.
PMID- 27512178
TI - Post-operative pneumothorax with subcutaneous emphysema in a pre-eclamptic
patient.
PMID- 27512179
TI - Erratum: Effect of addition of dexmedetomidine to ropivacaine 0.2% for femoral
nerve block in patients undergoing unilateral total knee replacement: A
randomised double blind study.
AB - [This corrects the article on p. 403 in vol. 60, PMID: 27330202.].
PMID- 27512180
TI - Indian Journal of Dermatology (IJD((r))) gets into the Science Citation Index
Expanded (SCIe).
PMID- 27512183
TI - Biostatistics Series Module 4: Comparing Groups - Categorical Variables.
AB - Categorical variables are commonly represented as counts or frequencies. For
analysis, such data are conveniently arranged in contingency tables.
Conventionally, such tables are designated as r * c tables, with r denoting
number of rows and c denoting number of columns. The Chi-square (chi(2))
probability distribution is particularly useful in analyzing categorical
variables. A number of tests yield test statistics that fit, at least
approximately, a chi(2) distribution and hence are referred to as chi(2) tests.
Examples include Pearson's chi(2) test (or simply the chi(2) test), McNemar's
chi(2) test, Mantel-Haenszel chi(2) test and others. The Pearson's chi(2) test is
the most commonly used test for assessing difference in distribution of a
categorical variable between two or more independent groups. If the groups are
ordered in some manner, the chi(2) test for trend should be used. The Fisher's
exact probability test is a test of the independence between two dichotomous
categorical variables. It provides a better alternative to the chi(2) statistic
to assess the difference between two independent proportions when numbers are
small, but cannot be applied to a contingency table larger than a two-dimensional
one. The McNemar's chi(2) test assesses the difference between paired
proportions. It is used when the frequencies in a 2 * 2 table represent paired
samples or observations. The Cochran's Q test is a generalization of the
McNemar's test that compares more than two related proportions. The P value from
the chi(2) test or its counterparts does not indicate the strength of the
difference or association between the categorical variables involved. This
information can be obtained from the relative risk or the odds ratio statistic
which is measures of dichotomous association obtained from 2 * 2 tables.
PMID- 27512184
TI - Methodology Series Module 4: Clinical Trials.
AB - In a clinical trial, study participants are (usually) divided into two groups.
One group is then given the intervention and the other group is not given the
intervention (or may be given some existing standard of care). We compare the
outcomes in these groups and assess the role of intervention. Some of the trial
designs are (1) parallel study design, (2) cross-over design, (3) factorial
design, and (4) withdrawal group design. The trials can also be classified
according to the stage of the trial (Phase I, II, III, and IV) or the nature of
the trial (efficacy vs. effectiveness trials, superiority vs. equivalence
trials). Randomization is one of the procedures by which we allocate different
interventions to the groups. It ensures that all the included participants have a
specified probability of being allocated to either of the groups in the
intervention study. If participants and the investigator know about the
allocation of the intervention, then it is called an "open trial." However, many
of the trials are not open - they are blinded. Blinding is useful to minimize
bias in clinical trials. The researcher should familiarize themselves with the
CONSORT statement and the appropriate Clinical Trials Registry of India.
PMID- 27512182
TI - Pityriasis Rosea: An Update on Etiopathogenesis and Management of Difficult
Aspects.
AB - Pityriasis rosea (PR) is a benign papulosquamous disorder seen commonly in
clinical practice. Despite its prevalence and benign nature, there are still
times when this common disorder presents in an uncommon way or course posing
diagnostic or management problems for the treating physician. The
etiopathogenesis of PR has always been a dilemma, and extensive research is going
on to elicit the exact cause. This review focuses mainly on the difficult aspects
of this benign common disorder such as etiopathogenesis, atypical manifestations,
recurrent cases, differential diagnosis, therapy and pregnancy considerations.
Although we could not find a black and white solution to all these problems, we
have tried to compile the related literature to draw out some conclusions.
PMID- 27512181
TI - Approach to Cutaneous Lymphoid Infiltrates: When to Consider Lymphoma?
AB - Cutaneous lymphoid infiltrates (CLIs) are common in routine dermatopathology.
However, differentiating a reactive CLI from a malignant lymphocytic infiltrate
is often a significant challenge since many inflammatory dermatoses can
clinically and/or histopathologically mimic cutaneous lymphomas, coined
pseudolymphomas. We conducted a literature review from 1966 to July 1, 2015, at
PubMed.gov using the search terms: Cutaneous lymphoma, cutaneous pseudolymphoma,
cutaneous lymphoid hyperplasia, simulants/mimics/imitators of cutaneous
lymphomas, and cutaneous lymphoid infiltrates. The diagnostic approach to CLIs
and the most common differential imitators of lymphoma is discussed herein based
on six predominant morphologic and immunophenotypic, histopathologic patterns:
(1) Superficial dermal T-cell infiltrates (2) superficial and deep dermal
perivascular and/or nodular natural killer/T-cell infiltrates (3) pan-dermal
diffuse T-cell infiltrates (4) panniculitic T-cell infiltrates (5) small cell
predominant B-cell infiltrates, and (6) large-cell predominant B-cell
infiltrates. Since no single histopathological feature is sufficient to discern
between a benign and a malignant CLI, the overall balance of clinical,
histopathological, immunophenotypic, and molecular features should be considered
carefully to establish a diagnosis. Despite advances in ancillary studies such as
immunohistochemistry and molecular clonality, these studies often display
specificity and sensitivity limitations. Therefore, proper clinicopathological
correlation still remains the gold standard for the precise diagnosis of CLIs.
PMID- 27512185
TI - Etiopathogenesis and Therapeutic Approach to Adult Onset Acne.
AB - Acne vulgaris is usually considered as a skin disorder that primarily affects
adolescents reaching a peak at the age of 14-17 years in females and 16-19 years
in males. However, recent epidemiologic studies have shown that a significant
number of female patients aged >25 years experience acne. As it is regarded as a
disease of teenagers, adults are more apprehensive and experience social anxiety.
Hence, adult onset acne has become a matter of concern.
PMID- 27512186
TI - Heat Shock Protein-70 Expression in Vitiligo and its Relation to the Disease
Activity.
AB - BACKGROUND: Vitiligo is a progressive depigmenting disorder characterized by the
loss of functional melanocytes from the epidermis. The etiopathogenesis of
vitiligo is still unclear. Heat shock proteins (HSPs) are prime candidates to
connect stress to the skin. HSPs were found to be implicated in autoimmune
diseases such as rheumatoid arthritis and other skin disorders as psoriasis. AIM
AND OBJECTIVES: The aim of this study was to map the level of HSP-70 in vitiligo
lesions to declare its role in the pathogenesis and activity of vitiligo.
MATERIALS AND METHODS: The study included thirty patients with vitiligo and 30
age- and sex-matched healthy controls. Vitiligo patients were divided as regards
to the disease activity into highly active, moderately active, and inactive
vitiligo groups. Skin biopsies were taken from the lesional and nonlesional skin
of patients and from the normal skin of the controls. HSP-70 messenger RNA (mRNA)
expression was estimated using quantitative real-time polymerase chain reaction.
RESULTS: Our analysis revealed a significantly higher expression of HSP-70 mRNA
in lesional skin biopsies from vitiligo patients compared to nonlesional skin
biopsies from vitiligo patients (P < 0.001) and compared to skin biopsies from
healthy controls (P < 0.001). The level of HSP-70 was not found to be correlated
with age, sex, or disease duration. The expression of HSP-70 was correlated with
the disease activity and patients with active vitiligo showed higher mean HSP-70
level compared to those with inactive disease. CONCLUSIONS: HSP-70 plays a role
in the pathogenesis of vitiligo and may enhance the immune response in active
disease.
PMID- 27512187
TI - A Comparative Study of Two Modalities, 4% Hydroquinone Versus 30% Salicylic Acid
in Periorbital Hyperpigmentation and Assessment of Quality of Life Before and
After Treatment.
AB - BACKGROUND: Periorbital hyperpigmentation (POH) is a common hyperpigmentary
problem of the face, which can be psychologically distressing and it can
influence an individual's quality of life. However, this condition has received
less attention in literature. AIMS AND OBJECTIVES: To study the clinico
etiological features and the effect of two therapeutic modalities on the quality
of life in patients of POH before and after treatment. MATERIALS AND METHODS:
Fifty patients attending the outpatient clinic of Dermatology Department, with
clinically evident POH were included. All patients were divided randomly into two
groups of 25 each and one group was treated with 4% hydroquinone and another
group with 30% salicylic acid for 12 weeks. Assessment with visual analog scale
(VAS) was done at 4, 6, and 12 weeks, and outcome of the patients was analyzed
statistically. RESULTS: Majority of the cases, i.e. 26 (52%) were in the age
group of 20-30 years. Females comprised 74% of the study population. On VAS, most
of the patients showed mild improvement (10-30%) at 12 weeks of treatment in both
the groups. Separately, both the treatments significantly improved the
dermatological life quality index of the patients although there was no
significant difference found between the two groups. CONCLUSION: POH is less
responsive to standard treatments due to its multifactorial etiology and
deposition of melanin in both dermis and epidermis. However, even the mild to
moderate improvement in appearance can cause an improvement in the quality of
life of the patients.
PMID- 27512188
TI - A Comparative Effectiveness Research of Azathioprine and Cyclophosphamide on the
Clinical and Serological Response in Pemphigus Vulgaris.
AB - CONTEXT: A prospective study was carried out to examine the efficacy of
cyclophosphamide and azathioprine in pemphigus vulgaris. AIMS: To compare the
clinical and serological effect of azathioprine and cyclophosphamide in pemphigus
patients. MATERIALS AND METHODS: Prospective, institutional based study was
conducted twenty-one patients of pemphigus vulgaris were initiated on either
azathioprine (n = 9) or cyclophosphamide (n = 7) in addition to prednisolone and
were evaluated clinically (mucosal and cutaneous severity) and serologically
enzyme-linked immunosorbent assay (ELISA) at 0, 3 and 6 months. RESULTS:
Azathioprine had a slower onset of action with a statistically significant
improvement seen by 6 months (P = 0.016). Cyclophosphamide had a faster onset of
action (3 months) though there was no statistical difference in the efficacy
between the two at the end of 6 months. The (RonT) was 33.3-44.4% for
azathioprine and 28.8-42.9% for cyclophosphamide at 6 months. Though ELISA had a
high sensitivity and specificity for diagnosis, as a tool for assessing
therapeutic response a significant decrease was seen only till 3 months. This was
restricted to Dsg1 for the azathioprine group and both Dsg3 and Dsg1 levels for
the cyclophosphamide group. There were two deaths, both in the cyclophosphamide
group. CONCLUSIONS: Azathiorpine and cyclophosphamide are equally effective for
mucosal and cutaneous disease in pemphigus after 6 months of therapy. Dsg ELISA
is useful for diagnosis of pemphigus but is not a useful tool for monitoring
response to therapy.
PMID- 27512189
TI - Long-lasting Localized Pemphigus Vulgaris without Detectable Serum Autoantibodies
Against Desmoglein 3 and Desmoglein 1.
AB - Pemphigus vulgaris (PV) is an autoimmune blistering disease elicited by anti
desmoglein (DsG) 3 antibody. Although skin lesions tend to be distributed over
the entire body, in some patients, they are confined to a restricted area. We
report two patients who presented with long-lasting localized PV without
detectable anti-DsG antibodies after suffering antibody-positive systemic PV.
Initial treatment with prednisolone (PSL) was successful in both patients, but a
local relapse occurred on the cheek or lower lip after a reduction in the PSL
dose. Biopsy of the localized lesions showed suprabasal acantholysis; no serum
DsG antibodies were found. Local immunosuppression therapy was effective in both
patients. Based on our findings, we suggest that localized PV without detectable
antibodies can develop after systemic PV.
PMID- 27512190
TI - Malignant Eccrine Poroma of the Vulva: An Intriguing Case of a Rare Tumor at an
Unusual Site.
AB - Malignant eccrine poroma is a rare malignancy of the eccrine sweat glands,
occurring most frequently on the lower extremities. It affects both sexes equally
usually in the 6(th) to 7(th) decade of life. Metastasis to regional lymph nodes
may occur in 20% that may be fatal in 60% cases. Its aggressive nature, rarity of
occurrence, and unusual presentations make it very important to be evaluated
properly by the clinician. We hereby report a case of a 75-year-old female
presenting with two exophytic tumors over her vulva with local extension. On
histopathological examination, it was diagnosed as malignant eccrine poroma. On
magnetic resonance imaging of the pelvic region, metastatic extension in regional
lymph nodes was found. She was treated by radical vulvectomy with bilateral
inguinal and femoral lymph node dissection followed by radiotherapy.
PMID- 27512191
TI - A Report of 10 Individuals with Weathering Nodules and Review of the Literature.
AB - Weathering nodules are a benign skin condition that usually present as papules on
the helices of patients with significant prior sun exposure. They are easily
recognized clinically and blanch upon application of pressure to the adjacent
helical rim: a positive blanch sign. We describe the clinical presentation of
weathering nodules in 10 patients, nine men and one woman, aging from 38 to 70
(median 59), and their associated risk factors. Eight patients had a history of
actinic keratosis, three had a history of nonmelanoma skin cancer, and all
patients had increased Sun exposure through outdoor activities. Weathering
nodules are rarely mentioned in the literature and may be confused with other
cutaneous disorders. Therefore, it is paramount for clinicians to become familiar
with weathering nodules and include them in the differential diagnosis of ear
nodules. Appropriate diagnosis will help avoid unnecessary biopsies while
reassuring the patient that the lesions are benign.
PMID- 27512192
TI - Chronic Eosinophilic Leukemia Presenting Predominantly with Cutaneous
Manifestations.
AB - A 37-year-old male presented with severe oral and genital mucosal ulcers,
lichenoid eruption and twenty-nail dystrophy. Systemic examination was normal,
except for anemia. On investigations, he was found to have persistently elevated
peripheral eosinophilia, absolute eosinophil count >5000/mm(3), bone marrow
showing increased eosinophilic precursors, and infiltration by atypical cells.
The serum vitamin B12 levels were grossly elevated, and Philadelphia chromosome
study was negative. Thus, a diagnosis of chronic eosinophilic leukemia was made.
The patient showed excellent response to imatinib mesylate. We are reporting a
rare type of leukemia presenting with predominantly cutaneous manifestations.
PMID- 27512193
TI - Curious Case of Photo-distributed Verrucae in a Renal Transplant Patient: Report
of Three Cases.
AB - Viral warts are a common lesion found in patients who have undergone a renal
transplant. The occurrence of verrucae also depends on the choice of
immunosuppressant and posttransplant time interval. The presence of viral warts
only on sun-exposed parts of the body is extremely uncommon and rarely reported.
It might also influence the choice of treatment since these warts are often
resistant to treatment.
PMID- 27512194
TI - Nodulocystic Basal Cell Carcinoma Arising Directly from a Seborrheic Keratosis: A
Rare Case Report.
AB - Seborrheic keratoses (SKs) are common epidermal tumors composed of benign
keratinocytes. Malignant skin tumors including basal cell carcinoma (BCC) rarely
arise within SKs. We report a rare case of an 82-year-old man with nodulocystic
BCC that appeared at the center of a scaly hyperpigmented SK that had been
presented for more than 10 years. It was histologically confirmed that CK19
positive BCC arose directly from the wall of the pseudohorn cyst, a part of the
SK. Nodular and/or cystic BCC also rarely arise within SKs while the most common
histologic type of BCC within SKs is the superficial type. Careful observation of
SKs is important even though it is rarely a background condition for malignant
transformation.
PMID- 27512195
TI - Drug-induced CD30+ Skin Lesions: Complex Interplay Between Infectious Agents,
Human Leukocyte Antigen System and Mast Cells/T Cells.
PMID- 27512196
TI - Author's Reply.
PMID- 27512197
TI - Late Onset Progressive Symmetric Erythrokeratoderma with Pseudo Ainhum.
PMID- 27512198
TI - Dermatosis Neglecta: An Increasingly Recognized Entity with Review of Literature.
PMID- 27512199
TI - Clues to Facial Demodicidosis: A Case Illustration.
PMID- 27512200
TI - Red and Black Pseudochromhidrosis.
PMID- 27512201
TI - Superficial Acral Fibromyxoma.
PMID- 27512202
TI - Monomorphic Papillae on Inner Labia and Vulvar Vestibule.
PMID- 27512203
TI - Erratum: Interstitial Granulomatous Drug Reaction After Intranasal Desmopressin
Administration.
AB - [This corrects the article on p. 125 in vol. 61.].
PMID- 27512204
TI - Treatment of Chronic Spontaneous Urticaria with a Single Dose of Omalizumab: A
Study of Four Cases.
AB - BACKGROUND: Chronic spontaneous urticaria (CSU) has a detrimental effect on
patients' emotional and physical quality of life. Omalizumab, an anti
immunoglobulin E humanized monoclonal antibody, has been shown to be very
effective in the treatment of refractory chronic urticaria patients but may not
be an economically viable option for all CSU patients. However, we present a case
series where a single dose of omalizumab gave sustained relief of symptoms in
patients with CSU, which may be an economical option. AIMS: The aim of this study
is to assess the efficacy of a single dose of omalizumab in the treatment of CSU.
MATERIALS AND METHODS: Four patients of CSU whose disease was not controlled with
four times the licensed dose of tablet fexofenadine 180 mg were exhibited one
subcutaneous injection of omalizumab and were followed up at 4 weekly intervals
for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7) and Dermatology Life
Quality Index (DLQI). RESULTS: A sharp decline in UAS7 and DLQI was documented in
7-10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in
the other three cases. Both the scores at the end of the follow-up period of 24
weeks were better than the pre-omalizumab scores. CONCLUSION: The results of this
case series indicate the efficacy of a single-dose omalizumab in treating
moderate to severe refractory CSU. Further studies are required to identify the
minimum frequency of administering omalizumab to effectively control CSU. This
would greatly reduce the cost of this novel therapy.
PMID- 27512205
TI - Folliculotropic Mycosis Fungoides in an Adolescent: A Rare Case.
AB - Folliculotropic mycosis fungoides (FMF) is an uncommon and aggressive form of
mycoses fungoides with preferential involvement of head and neck region. Lesions
of FMF present as erythematous plaques or papules with follicular prominences,
acneiform lesions, cysts, nodules, patches of scarring alopecia, and prurigo-like
lesions. The mean age of diagnosis is at 60 years and it is extremely rare in
childhood and adolescence. We report a case of a 16-year-old male patient who
presented with a 2-month history of an asymptomatic erythematous infiltrated
plaque over the forehead. Histological examination was consistent with diagnosis
of FMF. He was successfully treated with local electron beam therapy.
PMID- 27512206
TI - Co-occurrence of Erythrosis Pigmentosa Mediofacialis and Erythromelanosis
Follicularis Faciei et Colli Associated with Keratosis Pilaris in an Adolescent
Female.
AB - Erythromelanosis follicularis faciei et colli (EFFC) is a rare disease
characterized by a triad of reddish-brown pigmentation, erythema and follicular
papules localized on face and neck and is usually described in males. Erythrosis
pigmentosa mediofacialis (also known as Brocq or erythrosis pigmentosa
peribuccalis) is a similar disorder of the mediofacial area but with female
predominance. We report a case of simultaneous occurrence of erythrosis
pigmentosa peribuccalis and EFFC associated with keratosis pilaris in an
adolescent female.
PMID- 27512207
TI - Primary Cutaneous Histoplasmosis in an Immunocompetent Host from a Nonendemic
Area.
AB - A 32-year-old male presented to Dermatology outpatient Department with complaints
of a single nonhealing ulcer on his right thigh. This lesion was there for the
last 1? months. It had begun as a small nodule and increased up to the present
size of 3 cm with an oozing and ulcerated surface and thickened everted margins.
The systemic investigations were normal which included hemogram, biochemistry,
including liver and renal function tests, chest X-ray, ultrasonography of
abdomen, computed tomography of the thorax, and abdomen. Skin biopsy revealed
multiple rounds to oval spores with surrounding halo intracellularly as well as
extracellularly. A diagnosis of deep fungal infection as histoplasmosis was made
and confirmed on culture.
PMID- 27512208
TI - Congenital Erythropoietic Porphyria with Undescended Testis.
AB - Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis
pathway that are characterized by acute neurovisceral symptoms, skin lesions, or
both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with
a mutation in the gene that codes for uroporphyrinogen III synthase leading to
accumulation of porphyrin in different tissues and marked cutaneous
photosensitivity. We report a case of CEP with infancy onset blistering,
photosensitivity, red colored urine, and teeth along with scarring. Examination
revealed an undescended testis of the left side. Mutation analysis revealed
mutation in the uroporphyrinogen III synthase gene (UROS) resulting in c. 56 A >
G (Tyr19Cys). The presence of undescended testis with a rare mutation in a case
of CEP which itself is an extremely rare condition make the case interesting.
PMID- 27512209
TI - Adult Onset of Xanthelasmoid Mastocytosis: Report of a Rare Entity.
AB - Xanthelasmoid or pseudoxanthomatous mastocytosis is an extremely rare variant of
diffuse cutaneous mastocytosis. Herein, we describe an adult male with cutaneous
mastocytosis showing multiple widespread yellowish ovoid papules like eruptive
xanthoma. A 60-year-old male visited our outpatient clinic with a 1-year history
of generalized yellowish, ovoid, and skin color papular eruption located on the
trunk, groin, extremities, with the modest pruritus. Vital signs were stable, and
Darier's sign was negative. No other subjective and objective signs were detected
during the examination. No abnormality was detected in his diagnostic laboratory
tests. Skin biopsy was taken, and histopathologic examination revealed
proliferation of mast cells with ovoid and spindle nuclei with distinct cytoplasm
borders around the capillaries, which was compatible with mastocytosis.
Antihistamine was prescribed for pruritus control which was successful, but
eruptions were persistent, and even 1-year phototherapy was not useful.
PMID- 27512210
TI - Distant Skin Metastases from Carcinoma Buccal Mucosa: A Rare Presentation.
AB - Cancer of the oral cavity makes up approximately 30% of all head and neck region
tumors. Skin metastasis is rare with an incidence ranging between 0.7% and 2.4%.
Skin metastasis usually occurs in the neck, scalp, and over the skin near the
primary site. We report a patient with carcinoma left buccal mucosa who presented
with distant skin metastases to the right side chest wall.
PMID- 27512211
TI - Dermatopathia Pigmentosa Reticularis: Report of a New Cases and Literature
Review.
AB - Dermatopathia pigmentosa reticularis (DPR) is a very rare autosomal dominant
ectodermal dysplasia caused by mutations in keratin 14 and characterized by the
triad of generalized reticulate hyperpigmentation, nonscarring alopecia, and
onychodystrophy. We report two Saudi brothers with DPR that had normal hair
shafts, as assessed by scanning and transmission electron microscopy.
PMID- 27512212
TI - Kindler's Syndrome: A Tale of Two Siblings.
AB - Kindler's syndrome (KS) is a rare inherited skin disease characterized by acral
blistering, photosensitivity, progressive poikiloderma, and cutaneous atrophy
along with different types of mucosal involvement. We hereby report KS in two
siblings. The case is being reported for its rarity and for emphasizing the
importance of considering this condition in the differential diagnosis of
disorders that may cause blistering, cutaneous atrophy, and/or poikilodermatous
skin changes. Besides, the presentation of the disease in two of the members of
the same family makes the case even more interesting.
PMID- 27512213
TI - Current state of orthopedic education in India.
PMID- 27512214
TI - Nonvascularized fibular grafting in nonunion of femoral neck fracture: A
systematic review.
AB - Nonunion of femoral neck fractures following primary fixation and neglected
femoral neck fracture in young adults is a challenging task. Every effort should
be directed toward hip joint salvage in these patients. Among different available
options of hip salvage, nonvascularized fibular graft (NVFG) osteosynthesis is
simple, easy to perform, and a successful technique. In this review, the
available literature on NVFG in neglected and nonunion femoral neck fractures has
been analyzed. After review of 15 articles on NVFG, the average nonunion rate was
estimated to be 7.86% (range 0-31%). Six articles that evaluated the preoperative
and postoperative osteonecrosis reported improvement in 50% patients. The
clinical and/or functional outcome was good to excellent in 56-96% patients
following fibular osteosynthesis. Few complications such as coxa vara deformity,
limb shortening, and intraarticular penetration of the graft or hardware have
been reported. However, there are minimal donor site morbidities such as mild
ankle pain, transient loss of toe flexors and extensors and transient lateral
popliteal nerve palsy.
PMID- 27512215
TI - Total enbloc spondylectomy for metastatic high grade spinal tumors: Early
results.
AB - BACKGROUND: High grade metastatic spinal tumors are most common and are invasive.
These patients can succumb to disease progression if not treated timely. Although
considered as invasive and morbid, total enbloc spondylectomy (TES) in selected
cases has better survival rates. The authors describe the results of TES for high
grade metastatic spinal tumors. MATERIALS AND METHODS: Five patients (four
females and one male) underwent TES for solitary metastatic vertebral lesion
between November 2012 and January 2014. These patients presented to us with
spinal instability, unrelenting severe spinal pain and/or with severe progressive
radiculopathy. Average age was 46.2 years (range 39-62 years). After complete
investigations, computed tomography scan, magnetic resonance imaging scan and
positron emission tomography (PET) scan, it was confirmed that these patients had
high grade solitary vertebral metastatic tumor. RESULTS: Average duration of
followup was 18 months (range 16-20 months). The average preoperative visual
analog scale score of 9.4 (range 9-10) improved to 2 (range 1-4) at last
followup. Average blood loss was 1440 mL (range 1000-2000 mL). Average duration
of surgery was 198 min (range 180-240 min). Significant pain relief was noticed
in each patient in the immediate postoperative period and during followups. These
patients attained complete functional activities of daily living with in a month.
The imaging showed implants in situ, no recurrence of tumor, and no activity on
PET scan at the final followup. CONCLUSION: The present series shows favorable
short term results of TES for solitary, metastatic, high grade vertebral body
tumors by a team approach.
PMID- 27512216
TI - Management of osteonecrosis of the femoral head: A novel technique.
AB - BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a debilitating disease in
orthopedics, frequently progressing to femoral head collapse and osteoarthritis.
It is thought to be a multifactorial disease. ONFH ultimately results in femoral
head collapse in 75-85% of untreated patients. Total hip arthroplasty (THA)
yields satisfactory results in the treatment of the end stage of the disease.
However, disease typically affects males between the ages of 20 and 40 years and
joint replacement is not the ideal option for younger patients. Recently,
mesenchymal stem cells and platelet rich plasma (PRP) have been used as an
adjunct to core decompression to improve clinical success in the treatment of
precollapse hips. MATERIALS AND METHODS: A prospective study of 40 hips in 30
patients was done. There were 19 males and 11 females with a mean age 36.7 +/-
6.93 years. The indication for the operation was restricted primarily to modified
Ficat stages IIb and III. 16 hips (40%) had stage IIb and 24 hips (60%) had stage
III ONFH. The period of follow up ranged between 36-50 months with a mean 41.4 +/
3.53 months. All patients were assessed clinically during pre- and post
operative period according to the Harris Hip Score (HHS), Visual Analog Score
(VAS) and radiologically by X-rays. Magnetic resonance imaging (MRI) was done
preoperatively to confirm the diagnosis and every 6 months postoperatively for
assessment of healing. The operative procedure include removal of necrotic area
with drilling then the cavity was filled with a composite of bone graft mixed
with PRP. RESULTS: The mean HHS improved from 46.0 +/- 7.8 preoperatively to
90.28 +/- 19 at the end of followup (P < 0.0001). The mean values of VAS were 78
+/- 21 and 35 +/- 19 at preoperatively period and final followup, respectively,
with an average reduction of 43 points. CONCLUSION: We found that the use of PRP
with collagen sheet can increase the reparable capacity after drilling of
necrotic segment in stage IIb and III ONFH.
PMID- 27512217
TI - Osteosynthesis of ununited femoral neck fracture by internal fixation combined
with iliac crest bone chips and muscle pedicle bone grafting.
AB - BACKGROUND: Ununited femoral neck fracture is seen commonly in developing
countries due to delayed presentation or failure of primary internal fixation.
Such fractures, commonly present with partial or total absorption of femoral
neck, osteonecrosis of femoral head in 8-30% cases with upward migration of
trochanter posing problem for osteosynthesis, especially in younger individuals.
Several techniques for treatment of such conditions are described like
osteotomies or nonvascularied cortical or cancellous bone grafting provided
varying degrees of success in terms of fracture union but unsatisfactory long
term results occurred due to varying incidence of avascular necrosis (AVN) of
femoral head. Moreover, in presence of AVN of femoral head neither free fibular
graft nor cancellous bone graft is satisfactory. The vascularied bone grafting by
deep circumflex iliac artery based on iliac crest bone grafting, free vascularied
fibular grafting and muscle pedicle periosteal grafting showed high incidence of
success rate. Osteosynthesis is the preferred treatment of choice in ununited
femoral neck fracture in younger individuals. MATERIALS AND METHODS: Of the 293
patients operated during the period from June 1977 to June 2009, 42 were lost to
followup. Seven patients with gluteus medius muscle pedicle bone grafting (MPBG)
were excluded. Thus, out of 244 patients, 208 (85.3%) untreated nonunion and 36
(14.7%) following failure of primary internal fixation were available for
studies. Time interval between the date of injury and operation in untreated
nonunion cases was mean 6.5 months and in failed internal fixation cases was mean
11.2 months. Ages of the patients varied from 16 to 55 years. Seventy patients
had partial and 174 had subtotal absorption of the femoral neck. Evidence of
avascular necrosis (AVN) femoral head was found histologically in 135 (54.3%) and
radiologically in 48 (19.7%) patients. The patients were operated by open
reduction of fracture, cannulated hip screw fixation, iliac crest bone chips and
quadratus femoris MPBG. RESULTS: The mean followup is 12.5 years (range 3-35).
The union of fractures occurred in 202 (82.8%), delayed union in 18 (7.3%), and
established nonunion in 24 (9.8%) patients. Full weight bearing was permitted at
16-22 weeks after union of fractures. Mean Harris hip score at the longest
followup was 85.5. Among the complications, superficial wound infection occurred
in 20 (8.2%), deep infection in seven (2.9%), and coxa vara in 39 (16%) patients.
Preoperative radiodensity of femoral head disappeared mostly after the union of
fracture whereas fresh radiodensity of femoral head appeared in 20 (8%) patients;
nine (45%) of them developed segmental collapse. CONCLUSION: Ununited femoral
neck fractureis characterized by absorption of femoral neck, posterior cortical
defect, smoothening and overriding of fracture surfaces with intervening fibrous
tissues associated with or without AVN of femoral head. The above method of
osteosynthesis rectified the above pathology and provided satisfactory results
with union of fractures in 90.1% patients at long term followup.
PMID- 27512218
TI - Reverse distal femoral locking compression plate a salvage option in nonunion of
proximal femoral fractures.
AB - BACKGROUND: When primary fixation of proximal femoral fractures with implants
fails, revision osteosynthesis may be challenging. Tracts of previous implants
and remaining insufficient bone stock in the proximal femur pose unique problems
for the treatment. Intramedullary implants like proximal femoral nail (PFN) or
surface implants like Dynamic Condylar Screw (DCS) are few of the described
implants for revision surgery. There is no evidence in the literature to choose
one implant over the other. We used the reverse distal femur locking compression
plate (LCP) of the contralateral side in such cases undergoing revision surgery.
This implant has multiple options of fixation in proximal femur and its curvature
along the length matches the anterior bow of the femur. We aimed to evaluate the
efficacy of this implant in salvage situations. MATERIALS AND METHODS: Twenty
patients of failed primary proximal femoral fractures who underwent revision
surgery with reverse distal femoral locking plate from February 2009 to November
2012 were included in this retrospective study. There were 18 subtrochanteric
fractures and two ipsilateral femoral neck and shaft fractures, which exhibited
delayed union or nonunion. The study included 14 males and six females. The mean
patient age was 43.6 years (range 22-65 years) and mean followup period was 52.1
months (range 27-72 months). Delayed union was considered when clinical and
radiological signs of union failed to progress at the end of four months from
initial surgery. RESULTS: All fractures exhibited union without any
complications. Union was assessed clinically and radiologically. One case of
ipsilateral femoral neck and shaft fracture required bone grafting at the second
stage for delayed union of the femoral shaft fracture. CONCLUSIONS: Reverse
distal femoral LCP of the contralateral side can be used as a salvage option for
failed fixation of proximal femoral fractures exhibiting nonunion.
PMID- 27512219
TI - Arthroscopic resection of the distal clavicle in osteoarthritis of the
acromioclavicular joint.
AB - BACKGROUND: Symptomatic acromioclavicular joint (ACJ) lesions are a common cause
of shoulder complaints that can be treated successfully with both conservative
and surgical methods. There are several operative techniques, including both open
and arthroscopic surgery, for excising the distal end of the clavicle. Here, we
present a new modified arthroscopic technique for painful osteoarthritis of the
ACJ and evaluate its clinical outcomes. Our hypothesis was that 4- to 7-mm
resection of the distal clavicle in an en bloc fashion would have several
advantages, including no bony remnants, maintenance of stability of the ACJ, and
reduced prevalence of heterotopic ossification, in addition to elimination of the
pathologic portion of the distal clavicle. MATERIALS AND METHODS: 20 shoulders of
20 consecutive patients with painful and isolated osteoarthritis of the ACJ who
were treated by arthroscopic en bloc resection of the distal clavicle were
included in the study. There were 10 males and 10 females with an average age of
56 years (range 42-70 years). The mean duration of followup was 6 years and 2
months (range 4-8 years 10 months). The results were evaluated using the
University of California Los Angeles (UCLA) shoulder rating score. RESULTS: The
overall UCLA score was 13.7 preoperatively, which improved to 33.4
postoperatively. All subscores were improved significantly (P < 0.001). There
were no specific complications at the latest followup. CONCLUSION: It is critical
in this procedure to resect the distal clavicle evenly from superior to inferior
in an en bloc fashion without any small bony remnants and to preserve the capsule
and acromioclavicular ligament superoposteriorly. This arthroscopic procedure is
a reliable and reproducible technique for painful osteoarthritis of the ACJ
lesions in active patients engaged in overhead throwing sports and heavy labor.
PMID- 27512220
TI - Assessment of survival rates compared according to the Tamai and Yamano
classifications in fingertip replantations.
AB - BACKGROUND: The fingertip is the most frequently injured and amputated segment of
the hand. There are controversies about defining clear indications for
microsurgical replantation. Many classification systems have been proposed to
solve this problem. No previous study has simultaneously correlated different
classification systems with replant survival rate. The aim of the study is to
compare the outcomes of fingertip replantations according to Tamai and Yamano
classifications. MATERIALS AND METHODS: 34 consecutive patients who underwent
fingertip replantation between 2007 and 2014 were retrospectively reviewed with
respect to the Tamai and Yamano classifications. The medical charts from record
room were reviewed. The mean age of the patients was 36.2 years. There were 30
men and 4 women. All the injuries were complete amputations. Of the 34 fingertip
amputations, 19 were in Tamai zone 2 and 15 were in Tamai zone 1. When all the
amputations were grouped in reference to the Yamano classification, 6 were type 1
guillotine, 8 were type 2 crush and 20 were type 3 crush avulsions. RESULTS: Of
the 34 fingertips, 26 (76.4%) survived. Ten (66.6%) of 15 digits replanted in
Tamai zone 1 and 16 (84.2%) of 19 digits replanted in Tamai zone 2 survived.
There were no replantation failures in Yamano type 1 injuries (100%) and only two
failed in Yamano type 2 (75%). Replantation was successful in 14 of 20 Yamano
type 3 injuries, but six failed (70%). The percentage of success rates was the
least in the hybridized groups of Tamai zone 1-Yamano type 2 and Tamai zone 1
Yamano type 3. Although clinically distinct, the survival rates between the
groups were not statistically significantly different. CONCLUSIONS: The level and
mechanism of injury play a decisive role in the success of fingertip
replantation. Success rate increases in proximal fingertip amputations without
crush injury.
PMID- 27512221
TI - Anterior cervical discectomy and fusion for noncontiguous cervical spondylotic
myelopathy.
AB - BACKGROUND: Noncontiguous cervical spondylotic myelopathy (CSM) is a special
degenerative disease because of the intermediate normal level or levels between
supra and infraabnormal levels. Some controversy exists over the optimal
procedure for two noncontiguous levels of CSM. The study was to evaluate the
outcomes of the anterior cervical discectomy and fusion (ACDF) with zero-profile
devices for two noncontiguous levels of CSM. MATERIALS AND METHODS: 17
consecutive patients with two noncontiguous levels of CSM operated between
December 2009 and August 2012 were included in the study. There were 12 men and 5
women with a mean age of 60.7 years (range 45-75 years). Involved disc levels
were C3/4 and C5/6 in 11 patients and C4/5 and C6/7 in six patients. Preoperative
plain radiographs, computed tomography (CT) with 3-D reconstruction and magnetic
resonance imaging (MRI) of the cervical spine were taken in all patients. All
radiographs were independently evaluated by 2 spine surgeons and 1 radiologist.
The outcomes were assessed by the average operative time, blood loss, Japanese
Orthopedic Association (JOA) score, improvement rate, neck dysfunction index
(NDI), swallowing quality of life (SWAL-QOL) score, the cervical lordosis and
complications. RESULTS: The mean followup was 48.59 months (range 24-56 months).
The average operative time and blood loss was 105.29 min and 136.47 ml,
respectively. The preoperative JOA score was 8.35, which significantly increased
to 13.7 at the final followup (P < 0.01). The NDI score was significantly
decreased from preoperative 13.06 to postoperative 3.35 (P < 0.01). The operation
also provided a significant increase in the cervical lordosis (P < 0.01) from
preoperative 10.17 degrees to postoperative 17.06 degrees . The fusion rate was
94.1% at 6 months postoperatively, and 100% at 12 months after surgery. The mean
SWAL-QOL score decreased from preoperative 68.06 to immediate postoperatively
65.65 and then increased to 67.65 at final followup. There was a statistically
significant difference between preoperative and immediate postoperatively values
(P < 0.05), but none between preoperative and at final followup (P > 0.05).
Cerebrospinal fluid leak, dysphagia and radiological adjacent segment
degeneration occurred in one patient, respectively. CONCLUSION: The ACDF with
zero-profile devices is generally effective and safe in treating two
noncontiguous levels of CSM.
PMID- 27512222
TI - Limb lengthening in achondroplasia.
AB - BACKGROUND: Stature lengthening in skeletal dysplasia is a contentious issue.
Specific guidelines regarding the age and sequence of surgery, methods and extent
of lengthening at each stage are not uniform around the world. Despite the need
for multiple surgeries, with their attendant complications, parents demanding
stature lengthening are not rare, due to the social bias and psychological
effects experienced by these patients. This study describes the outcome and
complications of extensive stature lengthening performed at our center. MATERIALS
AND METHODS: Eight achondroplasic and one hypochondroplasic patient underwent
bilateral transverse lengthening for tibiae, humeri and femora. Tibia lengthening
was carried out using a ring fixator and bifocal corticotomy, while a monolateral
pediatric limb reconstruction system with unifocal corticotomy was used for the
femur and humerus. Lengthening of each bone segment, height gain, healing index
and complications were assessed. Subgroup analysis was carried out to assess the
effect of age and bone segment on the healing index. RESULTS: Nine patients aged
five to 25 years (mean age 10.2 years) underwent limb lengthening procedures for
18 tibiae, 10 femora and 8 humeri. Four patients underwent bilateral lengthening
of all three segments. The mean length gain for the tibia, femur and humerus was
15.4 cm (100.7%), 9.9 cm (52.8%) and 9.6 cm (77.9%), respectively. Healing index
was 25.7, 25.6 and 20.6 days/cm, respectively, for the tibia, femur and humerus.
An average of 33.3% height gain was attained. Lengthening of both tibia and femur
added to projected height achieved as the 3(rd) percentile of standard height in
three out of four patients. In all, 33 complications were encountered (0.9
complications per segment). Healing index was not affected by age or bone
segment. CONCLUSION: Extensive limb lengthening (more than 50% over initial
length) carries significant risk and should be undertaken only after due
consideration.
PMID- 27512223
TI - Relation between the development of osteoporosis and osteonecrosis following
glucocorticoid in a rabbit model.
AB - BACKGROUND: There has been a recent increase in the number of patients suffering
from bone and joint diseases, as a consequence of corticosteroids administration.
There are more patients treated with low dose of GCs under long-term conditions
in clinical, such as effect of GCs on Rheumatoid arthritis, Crohn's disease and
Asthma patients. Hence, it was difficult for doctor to determine which problem
occur first - OP or ON; however, there was no clinical report previously in the
literature, and there was no effective animal model of OP and ON about low dose
GCs. This study was conducted to develop rabbit models of glucocorticoid (GC)
induced femoral head ON and OP and to investigate the temporal relationship
between the occurrence of the two events following administration of
glucocorticoids. MATERIALS AND METHODS: Fifty six, 6 months old female rabbits
were randomly divided into the GC group and control group (C). Rabbits received
gluteal injections of methylprednisolone sodium succinate once a day for 4 weeks,
while normal saline solution in the control group. Rabbits were sacrificed at 0,
2, 4, and 8 weeks. Hip magnetic resonance imaging was performed before the
rabbits were sacrificed. Serum calcium (Ca), phosphorus (P), total cholesterol,
and triglyceride levels were also measured. The bone mineral density (BMD) of
femoral head and the femoral shaft were measured by dual-energy X-ray
absorptiometry. The trabecular parameters of the femur and the 4(th) lumbar
vertebrae (L4) were measured with a micro-computed tomography (MU-CT). Also, the
femoral head was stained with hematoxylin-eosin staining. RESULTS: At 4 weeks in
the GC group, the BMD of the femur reduced 33% and 22% in the femoral head and
shaft; there was irregular intermediate to high T2-weighted images signals; MU-CT
showed microfractures and cystic changes in the femoral head and L4 at 4 weeks.
At 8 weeks in the GC group, the classical "line-like sign" indicating ON of the
femoral head was observed in 64.3% of the rabbits. CONCLUSION: A rabbit model of
GC-induced OP and ON was developed by repetitive injection with small doses of
GCs in the gluteal region. OP was observed at 4 weeks while ON developed at 8
weeks and followed a clear temporal pattern.
PMID- 27512224
TI - Effect of insulin-like growth factor-1 and hyaluronic acid in experimentally
produced osteochondral defects in rats.
AB - BACKGROUND: The common purpose of almost all methods used to treat the
osteochondral injuries is to produce a normal cartilage matrix. However current
methods are not sufficient to provide a normal cartilage matrix. For that reason,
researchers have studied to increase the effectiveness of this methods using
chondrogenic and chondroprotective molecules in recent experimental studies.
Insulin-like growth factor-1 (IGF-1) and hyaluronic acid (HA) are two important
agents used in this field. This study compared the effects of IGF-1 and HA in an
experimental osteochondral defect in rat femora. MATERIALS AND METHODS: The rats
were divided into three groups (n = 15 per group) as follows: The IGF-1 group, HA
group, and control group. An osteochondral defect of a diameter of 1.5 mm and a
depth of 2 mm was created on the patellar joint side of femoral condyles. The IGF
1 group received an absorbable gelatin sponge soaked with 15 MUg/15 MUl of IGF-1,
and the HA group received an absorbable gelatin sponge soaked with 80 MUg HA. The
control group received only an absorbable gelatin sponge. Rats were sacrificed at
the 6(th) week, and the femur condyles were evaluated histologically. RESULTS:
According to the total Mankin scale, there was a statistically significant
difference between IGF-1 and HA groups and between IGF-1 and control groups.
There was also a significant statistical difference between HA and control
groups. CONCLUSION: It was shown histopathologically that IGF-1 is an effective
molecule for osteochondral lesions. Although it is weaker than IGF-1, HA also
strengthened the repair tissue.
PMID- 27512225
TI - N-terminal telopeptides of type I collagen and bone mineral density for early
diagnosis of nonunion: An experimental study in rabbits.
AB - BACKGROUND: The diagnosis and treatment of bone nonunion have been studied
extensively. Diagnosis and treatment of nonunion are mainly performed based on
the interpretation of clinico-radiographic findings, which depend on the
clinician's experience and the degree of bone callus formation during the
fracture-healing process. However, resolution may be compromised when the bone
mineral content is <25%. A feasible method of monitoring bone-healing is
therefore needed. We monitored a rabbit model of bone nonunion by regular
radiographic examinations, QCT detection, and biomarker concentrations. MATERIALS
AND METHODS: Twenty purebred New Zealand rabbits (10 male and 10 female, 5-6
months of age, 2.5-3.0 kg) were divided into bone defect Group (I) that 10 left
radius bones underwent resection of 1.5 cm of mid-radius bone and bone fracture
Group (II) that another 10 left radius bones underwent only mid-radius fracture.
Quantitative computed tomography detection of bone mineral density (BMD) and
serum markers of bone formation (osteocalcin [OC], bone-specific alkaline
phosphatase) and bone resorption (C- and N-terminal telopeptides of type I
collagen (NTX) and tartrate-resistant acid phosphatase 5b) were assayed. There
are twenty rabbits (10 male and 10 females). The age was 5-6 months weighing 2.5
3.0 kg). The defect was created in middle 1/3 radius in 10 rabbits and fracture
was created in middle 1/3 radius of 10 rabbits. RESULTS: BMD and NTX
concentrations were significantly lower at 5 weeks postoperatively compared to
the preoperative values and were significantly different between the two groups.
OC showed no significant difference before and after surgery. CONCLUSIONS: BMD
and NTX concentrations may be useful for early detection of bone nonunion in
rabbits.
PMID- 27512226
TI - Decalcified allograft in repair of lytic lesions of bone: A study to evolve bone
bank in developing countries.
AB - BACKGROUND: The quest for ideal bone graft substitutes still haunts orthopedic
researchers. The impetus for this search of newer bone substitutes is provided by
mismatch between the demand and supply of autogenous bone grafts. Bone banking
facilities such as deep frozen and freeze-dried allografts are not so widely
available in most of the developing countries. To overcome the problem, we have
used partially decalcified, ethanol preserved, and domestic refrigerator stored
allografts which are economical and needs simple technology for procurement,
preparation, and preservation. The aim of the study was to assess the
radiological and functional outcome of the partially decalcified allograft (by
weak hydrochloric acid) in patients of benign lytic lesions of bone. Through this
study, we have also tried to evolve, establish, and disseminate the concept of
the bone bank. MATERIALS AND METHODS: 42 cases of lytic lesions of bone who were
treated by decalcified (by weak hydrochloric acid), ethanol preserved, allografts
were included in this prospective study. The allograft was obtained from freshly
amputated limbs or excised femoral heads during hip arthroplasties under strict
aseptic conditions. The causes of lytic lesions were unicameral bone cyst (n =
3), aneurysmal bone cyst (n = 3), giant cell tumor (n = 9), fibrous dysplasia (n
= 12), chondromyxoid fibroma, chondroma, nonossifying fibroma (n = 1 each),
tubercular osteomyelitis (n = 7), and chronic pyogenic osteomyelitis (n = 5). The
cavity of the lesion was thoroughly curetted and compactly filled with matchstick
sized allografts. RESULTS: Quantitative assessment based on the criteria of Sethi
et al. (1993) was done. There was complete assimilation in 27 cases, partial
healing in 12 cases, and failure in 3 cases. Functional assessment was also done
according to which there were 29 excellent results, 6 good, and 7 cases of
failure (infection, recurrence, and nonunion of pathological fracture). We
observed that after biological incorporation, the graft participates in bone
physiology and morphology. We did not observe any adverse host graft antigenic
reaction. CONCLUSIONS: We conclude that decalcified allograft is suitable
alloimplant for use in benign lesions of bone, is easy to prepare and store, and
is thus well suited for use in developing countries.
PMID- 27512227
TI - Caveats of bisphosphonate abuse.
AB - BACKGROUND: Bisphosphonates (BPs) are the common drugs used for the treatment of
postmenopausal osteoporosis. Short term benefits of the BPs are well known.
However, there are concerns regarding their long term use. The aim of the study
was to analyze the association between atypical femoral fractures and BP
misuse/abuse as well as study the outcome of management of these fractures.
MATERIALS AND METHODS: A retrospective study of a prospectively studied patients
who presented with atypical femoral fractures between January 2010 and August
2012 and were followed up upto June 2014. The cohort consisted of nine female
patients (12 fractures) with an average age of 71 years (range 58-85 years).
Analysis was done for the indications, duration of BP use, configuration of
associated fractures and method of treatment. RESULTS: The mean duration of BP
use was 6.6 years (range 4-10 years). BP treatment was initiated without
sufficient indication and continued without proper review and followup in most
cases. Most patients did not followup and continued to consume BPs without any
review by the doctors. All patients had prodromal thigh pain of various duration,
which was inadequately investigated and managed before the presentation. Two
cases with an incomplete fracture and no thigh pain were managed successfully
with conservative treatment. The rest were treated by surgery with intramedullary
nailing. The average union time was longer and two fractures went into nonunion
which required further surgical intervention. CONCLUSION: Atypical femoral
fractures appear to be strongly related to abuse of BPs. Great care is to be
exercised at initiation as well as the continuation of BP therapy, and regular
review is required. There is a need for improved awareness among physicians about
the possibility of such fractures, and interpretation of thigh pain and
radiological findings, especially if the patient has been on BPs therapy.
Internal fixation for complete fractures and for incomplete fractures with thigh
pain is needed. Delayed union is common.
PMID- 27512228
TI - Lumbar epidural varices: An unusual cause of lumbar claudication.
AB - Lumbar epidural varices can also present with radiculopathy similar to acute
intervertebral disc prolapse (IVDP). However as the magnetic resonance imaging
(MRI) in these patients are usually normal without significant compressive
lesions of the nerve roots, the diagnosis is commonly missed or delayed leading
to persistent symptoms. We present a rare case of acute severe unilateral
claudication with a normal MRI unresponsive to conservative management who was
treated surgically. The nerve root on the symptomatic side was found to be
compressed by large anterior epidural varices secondary to an abnormal cranial
attachment of ligamentum flavum. Decompression of the root and coagulation of the
varices resulted in complete pain relief. To conclude, lumbar epidural varices
should be considered in the differential diagnosis of acute onset radiculopathy
and claudication in the absence of significant MRI findings.
PMID- 27512229
TI - Complete dorsal dislocation of the carpal scaphoid with perilunate dorsal
dislocation.
AB - Complete dorsal dislocation of the carpal scaphoid combined with dorsal
perilunate dislocation is an extremely rare carpal injury. We describe the case
of a 23-year-old man who presented with a complete dorsal dislocation of the
carpal scaphoid, combined with a perilunate dislocation. Surgical treatment was
performed with open reduction and interosseus ligament repair. At 4 years follow
up, the patient's wrist pain had completely resolved without limitations of wrist
joint motion and without evidence of avascular necrosis of the carpal scaphoid.
PMID- 27512230
TI - Early results of displaced supracondylar fractures of humerus in children treated
by closed reduction and percutaneous pinning.
PMID- 27512231
TI - Author's reply.
PMID- 27512232
TI - Erratum: Surgical hip dislocation for treatment of cam femoroacetabular
impingement.
AB - [This corrects the article on p. 496 in vol. 49, PMID: 26538754.].
PMID- 27512233
TI - Synthesis of 18F-Arenes from Spirocyclic Iodonium(III) Ylides via Continuous-Flow
Microfluidics.
AB - Spirocyclic hypervalent iodine(III) ylides have proven to be synthetically
versatile precursors for efficient radiolabelling of a diverse range of non
activated (hetero)arenes, highly functionalised small molecules, building blocks
and radiopharmaceuticals from [18F]fluoride ion. Herein, we report the
implementation of these reactions onto a continuous-flow microfluidic platform,
thereby offering an alterative and automated synthetic procedure of a
radiopharmaceutical, 3-[18F]fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile
([18F]FPEB) and a routinely used building block for click-radiochemistry, 4
[18F]fluorobenzyl azide. This new protocol was applied to the synthesis of
[18F]FPEB (radiochemical conversion (RCC) = 68 +/- 5%) and 4-[18F]fluorobenzyl
azide (RCC=68 +/- 5%; isolated radiochemical yield = 24+/-0%). We anticipate that
the high throughput microfluidic platform will accelerate the discovery and
applications of 18F-labelled building blocks and labelled compounds prepared by
iodonium ylide precursors as well as the production of radiotracers for
preclinical imaging studies.
PMID- 27512234
TI - Identifying the physical features of marina infrastructure associated with the
presence of non-native species in the UK.
AB - Marine invasive non-native species (NNS) are one of the greatest threats to
global marine biodiversity, causing significant economic and social impacts.
Marinas are increasingly recognised as key reservoirs for invasive NNS. They
provide submersed artificial habitat that unintentionally supports the
establishment of NNS introduced from visiting recreational vessels. While ballast
water and shipping vectors have been well documented, the role of recreational
vessels in spreading NNS has been relatively poorly studied. Identification of
the main physical features found within marinas, which relate to the presence of
NNS, is important to inform the development of effective biosecurity measures and
prevent further spread. Towards this aim, physical features that could influence
the presence of NNS were assessed for marinas throughout the UK in July 2013.
Thirty-three marine and brackish NNS have been recorded in UK marinas, and of the
88 marinas studied in detail, 83 contained between 1 and 13 NNS. Significant
differences in freshwater input, marina entrance width and seawall length were
associated with the presence of NNS. Additionally, questionnaires were
distributed to marina managers and recreational vessel owners to understand
current biosecurity practices and attitudes to recreational vessel biosecurity.
The main barriers to biosecurity compliance were cited as cost and time. Further
work identifying easily distinguished features of marinas could be used as a
proxy to assess risk of invasion.
PMID- 27512235
TI - Computational Simulation of Equivalence Class Formation Using the go/no-go
Procedure with Compound Stimuli.
AB - Research about equivalence has commonly utilized human participants as
experimental subjects. More recently, computational models have been capable of
reproducing performances observed in experiments with humans. The computational
model often utilized is called RELNET, and it simulates training and testing
trials of conditional relations using the matching-to-sample procedure (MTS). The
differentiation between sample stimulus and comparison stimuli, indispensable in
MTS, implies operational difficulties for simulations. For this reason, new
studies seek to utilize alternative procedures to MTS, which do not differentiate
the functions of the antecedent stimuli. This work evaluated the possibility of
developing a new computational model to simulate equivalence class formation
using the go/no-go procedure with compound stimuli. In Experiment 1, artificial
neural networks were utilized to simulate training of the AB and BC relations as
well as the testing of the AC relation. The results showed that four out of six
runs demonstrated equivalence class formation. Experiment 2 evaluated whether the
additional class training performed in Experiment 1, which was analogous to the
simulation of pre-experimental experience of human participants, would be
essential for simulating the establishment of equivalence classes. It was found
that it was not possible to simulate equivalence class formation without the
additional class training. Altogether, the experiments show that it is possible
to simulate equivalence class formation using the go/no-go procedure with
compound stimuli and that it is necessary to conduct additional class training.
The model developed is, therefore, an alternative to RELNET for the study of
equivalence relations using computational simulations.
PMID- 27512236
TI - The Inappropriate Symmetries of Multivariate Statistical Analysis in Geometric
Morphometrics.
AB - In today's geometric morphometrics the commonest multivariate statistical
procedures, such as principal component analysis or regressions of Procrustes
shape coordinates on Centroid Size, embody a tacit roster of symmetries-axioms
concerning the homogeneity of the multiple spatial domains or descriptor vectors
involved-that do not correspond to actual biological fact. These techniques are
hence inappropriate for any application regarding which we have a-priori
biological knowledge to the contrary (e.g., genetic/morphogenetic processes
common to multiple landmarks, the range of normal in anatomy atlases, the
consequences of growth or function for form). But nearly every morphometric
investigation is motivated by prior insights of this sort. We therefore need new
tools that explicitly incorporate these elements of knowledge, should they be
quantitative, to break the symmetries of the classic morphometric approaches.
Some of these are already available in our literature but deserve to be known
more widely: deflated (spatially adaptive) reference distributions of Procrustes
coordinates, Sewall Wright's century-old variant of factor analysis, the
geometric algebra of importing explicit biomechanical formulas into Procrustes
space. Other methods, not yet fully formulated, might involve parameterized
models for strain in idealized forms under load, principled approaches to the
separation of functional from Brownian aspects of shape variation over time, and,
in general, a better understanding of how the formalism of landmarks interacts
with the many other approaches to quantification of anatomy. To more powerfully
organize inferences from the high-dimensional measurements that characterize so
much of today's organismal biology, tomorrow's toolkit must rely neither on
principal component analysis nor on the Procrustes distance formula, but instead
on sound prior biological knowledge as expressed in formulas whose coefficients
are not all the same. I describe the problems of the standard techniques, discuss
several examples of the alternatives, and draw some conclusions.
PMID- 27512238
TI - Response of Development and Body Mass to Daily Temperature Fluctuations: a Study
on Tribolium castaneum.
AB - Differences in thermal regimes are of paramount importance in insect development.
However, experiments that examine trait development under constant temperature
conditions may yield less evolutionarily relevant results than those that take
naturally occurring temperature fluctuations into account. We investigated the
effect of different temperature regimes (constant 30 degrees C, constant 35
degrees C, fluctuating with a daily mean of 30 degrees C, or fluctuating with a
daily mean of 35 degrees C) on sex-specific development time and body mass in
Tribolium castaneum. Using a half-sib breeding design, we also examined whether
there is any evidence for genotype-by-environment interactions (GEI) for the
studied traits. In response to fluctuating temperature regimes, beetles
demonstrated reaction norm patterns in which thermal fluctuations influenced
traits negatively above the species' thermal optimum but had little to no effect
close to the thermal optimum. Estimated heritabilities of development time were
in general low and non-significant. In case of body mass of pupae and adults,
despite significant genetic variance, we did not find any GEI due to crossing of
reaction norms, both between temperatures and between variability treatments. We
have observed a weak tendency towards higher heritabilities of adult and pupa
body mass in optimal fluctuating thermal conditions. Thus, we have not found any
biasing effect of stable thermal conditions as compared to fluctuating
temperatures on the breeding values of heritable body-size traits. Contrary to
this we have observed a strong population-wide effect of thermal fluctuations,
indicated by the significant temperature-fluctuations interaction in both adult
and pupa mass.
PMID- 27512237
TI - Phenotypic Novelty in EvoDevo: The Distinction Between Continuous and
Discontinuous Variation and Its Importance in Evolutionary Theory.
AB - The introduction of novel phenotypic structures is one of the most significant
aspects of organismal evolution. Yet the concept of evolutionary novelty is used
with drastically different connotations in various fields of research, and debate
exists about whether novelties represent features that are distinct from standard
forms of phenotypic variation. This article contrasts four separate uses for
novelty in genetics, population genetics, morphology, and behavioral science,
before establishing how novelties are used in evolutionary developmental biology
(EvoDevo). In particular, it is detailed how an EvoDevo-specific research
approach to novelty produces insight distinct from other fields, gives the
concept explanatory power with predictive capacities, and brings new consequences
to evolutionary theory. This includes the outlining of research strategies that
draw attention to productive areas of inquiry, such as threshold dynamics in
development. It is argued that an EvoDevo-based approach to novelty is inherently
mechanistic, treats the phenotype as an agent with generative potential, and
prompts a distinction between continuous and discontinuous variation in
evolutionary theory.
PMID- 27512239
TI - Interagency Collaborative Team Model for Capacity Building to Scale-Up Evidence
Based Practice.
AB - BACKGROUND: System-wide scale up of evidence-based practice (EBP) is a complex
process. Yet, few strategic approaches exist to support EBP implementation and
sustainment across a service system. Building on the Exploration, Preparation,
Implementation, and Sustainment (EPIS) implementation framework, we developed and
are testing the Interagency Collaborative Team (ICT) process model to implement
an evidence-based child neglect intervention (i.e., SafeCare(r)) within a large
children's service system. The ICT model emphasizes the role of local agency
collaborations in creating structural supports for successful implementation.
METHODS: We describe the ICT model and present preliminary qualitative results
from use of the implementation model in one large scale EBP implementation.
Qualitative interviews were conducted to assess challenges in building system,
organization, and home visitor collaboration and capacity to implement the EBP.
Data collection and analysis centered on EBP implementation issues, as well as
the experiences of home visitors under the ICT model. RESULTS: Six notable issues
relating to implementation process emerged from participant interviews,
including: (a) initial commitment and collaboration among stakeholders, (b)
leadership, (c) communication, (d) practice fit with local context, (e) ongoing
negotiation and problem solving, and (f) early successes. These issues highlight
strengths and areas for development in the ICT model. CONCLUSIONS: Use of the ICT
model led to sustained and widespread use of SafeCare in one large county.
Although some aspects of the implementation model may benefit from enhancement,
qualitative findings suggest that the ICT process generates strong structural
supports for implementation and creates conditions in which tensions between EBP
structure and local contextual variations can be resolved in ways that support
the expansion and maintenance of an EBP while preserving potential for public
health benefit.
PMID- 27512240
TI - Cryptotephras: the revolution in correlation and precision dating.
AB - From its Icelandic origins in the study of visible tephra horizons,
tephrochronology took a remarkable step in the late 1980 s with the discovery of
a ca. 4300-year-old microscopic ash layer in a Scottish peat bog. Since then, the
search for these cryptotephra deposits in distal areas has gone from strength to
strength. Indeed, a recent discovery demonstrates how a few fine-grained glass
shards from an Alaskan eruption have been dispersed more than 7000 km to northern
Europe. Instantaneous deposition of geochemically distinct volcanic ash over such
large geographical areas gives rise to a powerful correlation tool with
considerable potential for addressing a range of scientific questions. A
prerequisite of this work is the establishment of regional tephrochronological
frameworks that include well-constrained age estimates and robust geochemical
signatures for each deposit. With distal sites revealing a complex record of
previously unknown volcanic events, frameworks are regularly revised, and it has
become apparent that some closely timed eruptions have similar geochemical
signatures. The search for unique and robust geochemical fingerprints thus hinges
on rigorous analysis by electron microprobe and laser ablation-inductively
coupled plasma-mass spectrometry. Historical developments and significant
breakthroughs are presented to chart the revolution in correlation and precision
dating over the last 50 years using tephrochronology and cryptotephrochronology.
PMID- 27512241
TI - Chronic exposure to a neonicotinoid pesticide alters the interactions between
bumblebees and wild plants.
AB - Insect pollinators are essential for both the production of a large proportion of
world crops and the health of natural ecosystems. As important pollinators,
bumblebees must learn to forage on flowers to feed both themselves and provision
their colonies.Increased use of pesticides has caused concern over sublethal
effects on bees, such as impacts on reproduction or learning ability. However,
little is known about how sublethal exposure to field-realistic levels of
pesticide might affect the ability of bees to visit and manipulate flowers.We
observed the behaviour of individual bumblebees from colonies chronically exposed
to a neonicotinoid pesticide (10 ppb thiamethoxam) or control solutions foraging
for the first time on an array of morphologically complex wildflowers (Lotus
corniculatus and Trifolium repens) in an outdoor flight arena.We found that more
bees released from pesticide-treated colonies became foragers, and that they
visited more L. corniculatus flowers than controls. Interestingly, bees exposed
to pesticide collected pollen more often than controls, but control bees learnt
to handle flowers efficiently after fewer learning visits than bees exposed to
pesticide. There were also different initial floral preferences of our treatment
groups; control bees visited a higher proportion of T. repens flowers, and bees
exposed to pesticide were more likely to choose L. corniculatus on their first
visit.Our results suggest that the foraging behaviour of bumblebees on real
flowers can be altered by sublethal exposure to field-realistic levels of
pesticide. This has implications for the foraging success and persistence of
bumblebee colonies, but perhaps more importantly for the interactions between
wild plants and flower-visiting insects and ability of bees to deliver the
crucial pollination services to plants necessary for ecosystem functioning.
PMID- 27512242
TI - A clinical comparative study of anatomic parameters before and after total hip
replacement on congenital dysplasia.
AB - [Purpose] To study preoperative and postoperative hip circumference data of
various types of congenital dysplasia of the hip treated with total hip
replacement, including the femoral offset, femoral neck length, height, and hip
abductor arm parameters. [Subjects and Methods] This study included seventy-eight
cases of congenital dysplasia of the hip (I-III type). Furthermore, four
parameters were measured, including the preoperative and postoperative femoral
offset. Statistical data analysis was performed using the SPSS 13.0 software.
[Results] The femoral offset was 33.3 +/- 8.4 mm (preoperative) and 39.1 +/- 7.1
mm (postoperative). The femoral head height was 59.5 +/- 8.7 mm (preoperative)
and 68.8 +/- 11.0 mm (postoperative). The femoral neck length was 50.8 +/- 10.8
mm (preoperative) and 61.5 +/- 10.4 mm (postoperative). The hip abductor arm was
54.3 +/- 9.6 mm (preoperative) 64.7 +/- 10.1 mm (postoperative). The preoperative
and postoperative parameters showed statistical differences. Furthermore, no
significant differences were evidenced when comparing the postoperative hip
parameters with the normal data parameters. [Conclusion] Total hip replacement on
congenital dysplasia of the hip could lead to the rebuilt of an almost normal
physiological anatomy for each hip case (type I-III).
PMID- 27512243
TI - The effect of exercise intervention on frail elderly in need of care: half-day
program in a senior day-care service facility specializing in functional
training.
AB - [Purpose] This study investigated the long-term effect of a half-day exercise
intervention program on health-related quality of life, life function, and
physical function in frail elderly in need of care. The program was conducted at
a senior day-care facility specializing in functional training. [Subjects and
Methods] Subjects included 41 elderly in need of care who had visited the service
facility for at least 1 year. Physical function and life function were evaluated
at baseline, 6 months, and 12 months. Quality of life was evaluated with the
Short Form-36 at baseline and 12 months. [Results] Improvements in balance,
walking speed and endurance, complex performance abilities, self-efficacy during
the activities, and the level and sphere of activity were observed at 6 months
and maintained up to 12 months. Moreover, improvements in agility, activities of
daily living, life function, and quality of life were also observed at 12 months.
Improvements in muscle strength, walking ability, self-efficacy over an action,
and activities of daily living were related to the improvement in quality of
life. [Conclusion] The use of individualized exercise programs developed by
physiotherapists led to improvements in activities of daily living and quality of
life among elderly in need of care.
PMID- 27512244
TI - Effect of chronic knee osteoarthritis on flexion-relaxation phenomenon of the
erector spinae in elderly females.
AB - [Purpose] This study investigated the flexion-relaxation phenomenon of the
erector spinae in elderly women with chronic knee osteoarthritis and determined
whether the flexion-relaxation phenomenon can be used as a pain evaluation tool
in such cases. [Subjects and Methods] Seventeen elderly females with chronic knee
osteoarthritis and 13 healthy young females voluntarily participated in this
study. They performed three postural positions in 15 s: trunk flexion, complete
trunk flexion, and trunk extension, each for 5 s. While these positions were
held, muscle activation of the thoracic and lumbar erector spinae were measured
using surface electromyography. The flexion-relaxation rate was determined by
dividing the values for trunk extension by those of complete trunk flexion and by
dividing the values for trunk flexion by those of complete trunk flexion.
[Results] According to our results, the flexion-relaxation phenomenon was
different between healthy young and elderly females with chronic knee
osteoarthritis. Specifically, there was a difference in the left thoracic erector
spinae muscle, but not in the left and right lumbar erector spinae or right
thoracic spinae muscle. [Conclusion] Our study demonstrated that the erector
spinae muscle flexion-relaxation phenomenon can be used as a pain evaluation tool
in elderly females with chronic knee osteoarthritis.
PMID- 27512245
TI - Raster-stereographic evaluation of the effects of biomechanical foot orthoses in
patients with scoliosis.
AB - [Purpose] Little is known about the effects of biomechanical foot orthoses in
scoliosis, as determined by raster stereography. The objective of this study was
to investigate the effect of individually manufactured biomechanical foot
orthoses on scoliosis angle, trunk imbalance, and pelvic obliquity by comparing
them with general insoles by using DIERS formetric 4 dimensional in patients with
scoliosis. [Subjects and Methods] Twenty-six patients with scoliosis were
recruited at Yeungnam University Hospital and allocated equally to one of two
groups, the biomechanical foot orthoses group or the control group. Parameters,
such as, trunk rotation, imbalance, and scoliosis angle, were obtained using a
DIERS formetric 4D. [Results] Scoliosis angle, pelvic obliquity, and trunk
imbalance were significantly different between the two groups and improved in the
biomechanical foot orthoses group with time, but no significant improvement in
any parameter was observed in the control group. [Conclusion] Biomechanical foot
orthoses could be effective in patients with scoliosis, and DIERS formetric 4D
provides a useful method for evaluating scoliosis parameters.
PMID- 27512246
TI - Design, development, and clinical validation of therapeutic toys for autistic
children.
AB - [Purpose] One of the characteristics of autistic children is social interaction
difficulties. Although therapeutic toys can promote social interaction, however
its related research remains insufficient. The aim of the present study was to
build a set of cooperative play toys that are suitable for autistic children.
[Subjects and Methods] This study used an innovative product design and
development approach as the basis for the creation of cooperative play toys.
[Results] The present study has successfully developed cooperative play toys.
Compared to the traditional game therapy for autism, cooperative play toy therapy
can significantly improve the interactions between autistic children and their
peers. [Conclusion] The most critical design theme of cooperative play toys
focuses on captivating the interest of autistic children. Based on the needs of
the individual cases, the design of the therapeutic toy set was specifically
tailored, i.e., by reinforcing the sound and light effects to improve the
attractiveness of the toys. In the future, different play modes can be combined
with this toy set to further enhance the degree of interaction of autistic
children and improve their quality of life and social skills.
PMID- 27512247
TI - Effect of sequential pneumatic compression therapy on venous blood velocity,
refilling time, pain and quality of life in women with varicose veins: a
randomized control study.
AB - [Purpose] The aim of this study was to investigate the effects of sequential
pneumatic compression therapy on venous blood flow, refilling time, pain level,
and quality of life in women with varicose veins. [Subjects and Methods] Twenty
eight females with varicose veins were selected and randomly allocated to a
control group, and experimental group. Maximum and mean venous blood velocities,
the refilling time, pain by visual analog scale and quality of life by Aberdeen
Varicose Veins Questionnaire were measured in all patients before and after six
weeks of treatment. Both groups received lower extremity exercises; in addition,
patients in the experimental group received sequential pneumatic compression
therapy for 30 minutes daily, five days a week for six weeks. [Results] All
measured parameters improved significantly in both groups, comparison of post
treatment measurements between groups showed that the maximum and mean blood flow
velocity, the pain level, and quality of life were significantly higher in the
experimental group compared with the control group. On the other hand there was
no significant difference between groups for refilling time. [Conclusion]
Sequential pneumatic compression therapy with the applied parameters was an
effective modality for increasing venous blood flow, reducing pain, and improving
quality of women life with varicose veins.
PMID- 27512248
TI - The effects of short-term use of compression stockings on health related quality
of life in patients with chronic venous insufficiency.
AB - [Purpose] This study was aimed to analyse the effects of short-term use of
compression stockings (CS) on symptoms and QoL in patients with Chronic Venous
Insufficiency (CVI). [Subjects and Methods] Based on the CEAP classification C2
and C3, 117 patients with CVI were enrolled in this study. The participants were
divided into two groups. The control group refused to use CS, however, was
advised to do exercises and take skin care whereas the CS group used CS and
performed exercise. The data were collected by using Nottingham Health Profile
(NHP), Venous Insufficiency Epidemiological and Economic Study (VEINES-QoL/Sym)
and Beck Depression Inventory (BDI) at baseline and after four weeks of treatment
and compared within and in between groups. [Results] The comparison of pre- and
post-treatment differences between groups was statistically significant for all
parameters. In the study group, pre- and post-treatment scores for each parameter
were significantly different. However, elevated scores in the control group
suggested worsening of the illness. [Conclusion] This study established that
short-term use of CS in patients with CVI significantly improved disease specific
and general QoL by reducing venous symptoms. Further studies with larger sample
size are necessary to confirm these findings.
PMID- 27512249
TI - Comparison of the efficacy of physical therapy and corticosteroid injection in
the treatment of pes anserine tendino-bursitis.
AB - [Purpose] The aims of this study were twofold. The first was to compare the
functional capacity and pain of patients with knee osteoarthritis (KOA), with or
without pes anserine tendino-bursitis (PATB). The second is to compare the
efficacy of two treatment methods (physical therapy and corticosteroid injection)
for patients with PATB. [Subjects and Methods] Sixty patient with KOA and PATB
(Group 1) and 57 patients with KOA but without PATB (Group 2) were enrolled in
the study. The patients' visual analog scale (VAS), Western Ontario and McMaster
Universities osteoarthritis index (WOMAC) scores and three-meter timed-up and go
scores were measured. The PATB group was randomly divided into two groups (Group
A and B). Physical therapy (PT) modalities were applied to the first group (Group
A), and the second group (Group B) received corticosteroid injections to the pes
anserine area. Eight weeks later, patients' parameters were measured again.
[Results] Initial WOMAC scores and timed up-and-go times were significantly
higher in Group 1 than in Group 2. Both treatments resulted in significant
improvements in all measured parameters, but no significant difference was
detected between Group A and B. [Conclusion] Patients with PATB tend to have more
severe pain, more altered functionality, and greater disability than those with
KOA but without PATB. Both corticosteroid injection and PT are effective methods
of treatment for PATB. Injection therapy can be considered an effective,
inexpensive and fast therapeutic method.
PMID- 27512251
TI - Effect of high-frequency repetitive transcranial magnetic stimulation on motor
cortical excitability and sensory nerve conduction velocity in subacute-stage
incomplete spinal cord injury patients.
AB - [Purpose] The aim of the present study was to determine whether repetitive
transcranial magnetic stimulation can improve sensory recovery of the lower
extremities in subacute-stage spinal cord injury patients. [Subjects and Methods]
This study was conducted on 20 subjects with diagnosed paraplegia due to spinal
cord injury. These 20 subjects were allocated to an experimental group of 10
subjects that underwent active repetitive transcranial magnetic stimulation or to
a control group of 10 subjects that underwent sham repetitive transcranial
magnetic stimulation. The SCI patients in the experimental group underwent active
repetitive transcranial magnetic stimulation and conventional rehabilitation
therapy, whereas the spinal cord injury patients in the control group underwent
sham repetitive transcranial magnetic stimulation and conventional rehabilitation
therapy. Participants in both groups received therapy five days per week for six
weeks. Latency, amplitude, and sensory nerve conduction velocity were assessed
before and after the six week therapy period. [Results] A significant intergroup
difference was observed for posttreatment velocity gains, but no significant
intergroup difference was observed for amplitude or latency. [Conclusion]
repetitive transcranial magnetic stimulation may be improve sensory recovery of
the lower extremities in subacute-stage spinal cord injury patients.
PMID- 27512250
TI - Comparison of upper extremity function, pain, and tactile sense between the
uneffected side of hemiparetic patients and healthy subjects.
AB - [Purpose] The aim of this study was to compare the unaffected upper extremity of
patients with hemiparesis with that of healthy subjects in terms of function,
pain, and tactile sense. [Subjects and Methods] Upper extremity evaluation
parameters of 20 patients with hemiparesis were compared with an age-matched
control group of 20 healthy subjects. A shorter version of the Disability of Arm
and Shoulder Questionnaire, Upper Extremity Functional Index, and Simple Shoulder
Test were used to evaluate the upper extremity functionality. The Visual Analog
Scale was used to measure pain severity at rest, at night, and during activity.
Tactile sensation levels were assessed by Semmes-Weinstein monofilaments at four
palmar areas. [Results] A statistically significant difference was found in the
upper extremity functionality between the groups. Pain severity at rest was
significantly higher in the hemiparetic group. There was no significant
difference in night and activity pain severities or tactile sensation levels
between the groups. [Conclusion] According to our results, the unaffected side of
patients with hemiparesis differs in functionality and pain at rest compared with
that of healthy persons. Studies with larger sample size and various evaluation
tests are needed to further investigate the unaffected side of patients with
hemiparesis.
PMID- 27512252
TI - Functional limitations due to foot involvement in spondyloarthritis.
AB - [Purpose] Spondyloarthritis is a major inflammatory disease followed-up in the
rheumatology clinics, foot involvement in spodyloarthritis is common. The
functional states of patients with spondyloarthritis are usually evaluated
globally. The aim of this study was to assess the foot involvement-related
functional limitations in patients with spondyloarthritis. [Subjects and Methods]
Patients with ankylosing spondylitis and psoriatic arthritis with foot pain more
than 4 weeks who underwent anteroposterior and lateral feet radiography were
enrolled into the study. A "clinical findings score" was calculated by assigning
1 point for every finding of swelling, redness, and tenderness. C-reactive
protein and erythrocyte sedimentation rate were used as serum markers for disease
activity. Foot radiograms were evaluated using the spondyloarthropathy tarsal
radiographic index and the foot-related functional state of patients was
determined by the Turkish version of the Foot and Ankle Outcome Score. [Results]
There were no relationships between Foot and Ankle Outcome Score subscales and
clinical findings score, serum markers, or radiologic score. Pain and symptoms
subscale scores were result positively correlated with activity of daily living,
sport and recreation, and quality of life subscale scores. [Conclusion] Pain and
symptoms are the main determinants of foot-related functional limitations in
spondyloarthritis.
PMID- 27512253
TI - Clinical effectiveness of a Pilates treatment for forward head posture.
AB - [Purpose] This study compared the effects of pilates and an exercise program on
the craniovertebral angle, cervical range of motion, pain, and muscle fatigue in
subjects with a forward head posture (FHP). [Subjects and Methods] A total of 28
sedentary females (age 20 to 39 years) with FHP were randomly assigned to pilates
(n=14) and combined (n=14) exercise groups. The study was a randomized,
controlled, double-blind study with the two groups performing exercise 50
min/day, 3 days/week, with an intensity of 11-15 rating of perceived exertion
(RPE) for ten weeks. The main outcome measures were craniovertebral angle,
cervical range of motion (ROM), pain levels assessed by visual analog scale
(VAS), and neck disability index (NDI). Surface electromyography was also used to
measure muscle fatigue. [Results] There were significant increases in
craniovertebral angle and cervical ROM in the pilates group, but none in the
control group. The only significant differences in muscle activity were recorded
in the sternocleidomastoid muscle in the pilates group. Both exercise programs
had positive effects on pain measures, as VAS and NDI were significantly
decreased. [Conclusion] The results suggest that pilates could be recommended as
an appropriate exercise for treatment of FHP in sedentary individuals.
PMID- 27512254
TI - Effects of trunk stability exercise using proprioceptive neuromuscular
facilitation with changes in chair height on the gait of patients who had a
stroke.
AB - [Purpose] The purpose of this study was to identify the effects of trunk
stability exercise using proprioceptive neuromuscular facilitation with changes
in chair heights on the gait of stroke patients. [Subjects and Methods] The
subjects of this study were 11 stroke patients. The intervention method was trunk
stability exercise using proprioceptive neuromuscular facilitation with different
chair heights (50, 60, and 70 cm). These exercises were performed 5 times per
week for 6 weeks. Gait velocity, cadence, stride length, gait cycle, and stance
phase duration were used to measure gait function. [Results] Significant changes
in gait velocity, cadence, and stride length were observed on the affected side.
However, no significant changes in gait cycle and stance phase were observed on
the affected side. [Conclusion] These results indicate that trunk stability
exercise using proprioceptive neuromuscular facilitation with change in chair
heights were effective in improving gait velocity, cadence, and stride length on
the affected side. However, in this study, no significant changes were observed
in gait cycle and stance phase on the affected side. Therefore, various
interventions for stroke patients should be investigated in further studies.
PMID- 27512255
TI - Canoe game-based virtual reality training to improve trunk postural stability,
balance, and upper limb motor function in subacute stroke patients: a randomized
controlled pilot study.
AB - [Purpose] This study was aimed at investigating the preliminary therapeutic
efficacy and usefulness of canoe game-based virtual reality training for stroke
patients. [Subjects and Methods] Ten stroke patients were randomly assigned to an
experimental group (EG; n=5) or a control group (CG; n=5). Patients in both
groups participated in a conventional rehabilitation program, but those in the EG
additionally participated in a 30-min canoe game-based virtual reality training
program 3 days a week for 4 weeks. Therapeutic efficacy was assessed based on
trunk postural stability, balance, and upper limb motor function. In addition,
the usefulness of canoe game-based virtual reality training was assessed in the
EG and therapist group (TG; n=20), which consisted of physical and occupational
therapists, by using the System Usability Scale (SUS). [Results] Improvements in
trunk postural stability, balance, and upper limb motor function were observed in
the EG and CG, but were greater in the EG. The mean SUS scores in the EG and TG
were 71 +/- 5.2 and 74.2 +/- 4.8, respectively. [Conclusion] Canoe game-based
virtual reality training is an acceptable and effective intervention for
improving trunk postural stability, balance, and upper limb motor function in
stroke patients.
PMID- 27512256
TI - The effects of gait time and trunk acceleration ratio during stair climbing in
old-old adult females.
AB - [Purpose] This study investigated the effects of gait time and trunk acceleration
ratio in old-old adult females during stair climbing. [Subjects and Methods]
Twenty-five older adult females who were able to walk independently volunteered
for this study and were categorized into two age groups (older adults or old-old
adults). Gait time and trunk acceleration ratio were measured using an
accelerometer during stair climbing. [Results] Gait time and trunk acceleration
ratio when climbing stairs were significantly higher in the old-old age group
than in the older adults group. [Conclusions] These findings suggest that old-old
females have decreased upper trunk control. In addition, gait time and the trunk
acceleration ratio during stair climbing are useful clinical markers for
predicting function and balance control ability in old-old elderly populations.
PMID- 27512257
TI - Zhoubo plus uncaria tincture in the treatment of cerebral concussion sequelae.
AB - [Purpose] This study investigated the clinical efficacy of the compound gouteng
tincture combined with Zhoubo (GT-ZB) in treating the sequelae of cerebral
concussion (CC) in children. [Subjects and Methods] Sixty children with CC
sequelae were randomily divided into a treatment group and a control group, with
30 cases in each group. The treatment group was treated using GT-ZB, and the
control group was treated using the standard method of venoruton, dibazol, and
Vitamin B6. The efficacies of the two treatments were compared. [Results]
Compared with the control group, the clinical symptoms and signs in the treatment
group were significantly mitigated. [Conclusion] GT-ZB demonstrated efficacy in
treating the sequelae of CC in children, and it is worthy of further studies and
possible clinical recommendations.
PMID- 27512258
TI - The immediate intervention effects of robotic training in patients after anterior
cruciate ligament reconstruction.
AB - [Purpose] The purpose of this study was to examine the immediate effects of robot
assisted therapy on functional activity level after anterior cruciate ligament
reconstruction. [Subjects and Methods] Participants included 10 patients (8 males
and 2 females) following anterior cruciate ligament reconstruction. The subjects
participated in robot-assisted therapy and treadmill exercise on different days.
The Timed Up-and-Go test, Functional Reach Test, surface electromyography of the
vastus lateralis and vastus medialis, and maximal extensor strength of isokinetic
movement of the knee joint were evaluated in both groups before and after the
experiment. [Results] The results for the Timed Up-and-Go Test and the 10-Meter
Walk Test improved in the robot-assisted rehabilitation group. Surface
electromyography of the vastus medialis muscle showed significant increases in
maximum and average discharge after the intervention. [Conclusion] The results
suggest that walking ability and muscle strength can be improved by robotic
training.
PMID- 27512259
TI - Short-term effects of kinesio tape on joint position sense, isokinetic
measurements, and clinical parameters in patellofemoral pain syndrome.
AB - [Purpose] To evaluate the short-term effects of kinesio tape on joint position
sense, isokinetic measurements, kinesiophobia, symptoms, and functional
limitations in patients with patellofemoral pain syndrome. [Subjects and Methods]
A total of 90 patients (112 knees) with patellofemoral pain syndrome were
randomized into a kinesio tape group (n=45) or placebo kinesio tape group (n=45).
Baseline isokinetic quadriceps muscle tests and measurements of joint position
sense were performed in both groups. Pain was measured with a Visual Analog
Scale, kinesiophobia with the Tampa kinesiophobia scale, and symptoms and
functional limitations with the Kujala pain scale. Measurements were repeated 2
days after kinesio tape application. [Results] No differences were found between
baseline isokinetic muscle measurements and those taken 2 days after application.
However, significant improvements were observed in the kinesio tape group, with
regard to joint position sense, pain, kinesiophobia, symptoms, and functional
limitations after treatment. Examination of the differences between pre- and post
treatment values in both groups revealed that the kinesio tape group demonstrated
greater improvements compared to the placebo kinesio tape group. [Conclusion]
Although short-term kinesio tape application did not increase hamstring muscle
strength, it may have improved joint position sense, pain, kinesiophobia,
symptoms, and daily limitations.
PMID- 27512260
TI - Effects of mental practice on normal adult balance ability.
AB - [Purpose] This study aimed to examine the effects of mental practice on the
balance abilities of normal individuals. [Subjects and Methods] Thirty subjects
were randomly assigned to an experimental or control group (n=15 each).
Participants in both groups performed balance training in a seated position on a
gym ball for 20 minutes per session, five sessions per week, for 4 weeks. Members
of the experimental group also performed mental practice for 10 minutes before
the balance training. After the intervention, balance measuring equipment (Good
Balance, Metitur, Finland) was used to quantitatively measure balance ability.
[Results] Significant post-training gains were observed in the mediolateral,
index of balance function, and time variables of participants of the experimental
group. [Conclusion] The application of mental practice with balance training
positively affected balance ability.
PMID- 27512261
TI - Effect of aquatic dual-task training on balance and gait in stroke patients.
AB - [Purpose] The purpose of this study was to determine the effect of aquatic dual
task training on balance and gait in stroke patients. [Subjects and Methods]
Twenty stroke patients were divided into the experimental (n=10) and control
(n=10) groups. Both groups underwent neurodevelopmental treatment. The
experimental group additionally underwent aquatic dual-task training for 30
minutes a day, 5 days a week, for 6 weeks. Balance was measured using the Berg
balance scale, Five Times Sit-to Stand Test, and Functional Reach Test. Gait was
measured using the 10-Meter Walk Test, Timed Up and Go Test, and Functional Gait
Assessment. [Results] For intragroup comparison, the experimental group showed a
significant change after the experiment in all balance and gait assessment tests.
For intergroup comparison, the experimental group showed relatively more
significant change after the experiment in all balance and gait assessment tests.
[Conclusion] Our results showed that aquatic dual-task training has a positive
effect on balance and gait in stroke patients.
PMID- 27512263
TI - The effect of virtual reality-based eccentric training on lower extremity muscle
activation and balance in stroke patients.
AB - [Purpose] The purpose of this study was to examine the effect of virtual reality
based eccentric training on lower extremity muscle activity and balance in stroke
patients. [Subjects and Methods] Thirty stroke patients participated, with 15
patients allotted to each of two eccentric training groups: one using a slow
velocity (group I) and one using a fast velocity (group II). The virtual reality
based eccentric training was performed by the patients for 30 minutes once a day,
5 days a week, for 8 weeks using an Eccentron system. Surface electromyography
was used to measure the lower extremity muscle activity, while a BioRescue was
used to measure balancing ability. [Results] A significant difference in lower
extremity muscle activation and balance ability was observed in group I compared
with group II. [Conclusion] This study showed that virtual reality-based
eccentric training using a slow velocity is effective for improving lower
extremity muscle activity and balance in stroke patients.
PMID- 27512262
TI - The impact of physical therapy in patients with severe traumatic brain injury
during acute and post-acute rehabilitation according to coma duration.
AB - [Purpose] The aim of study was to evaluate the impact of physical therapy on the
recovery of motor and mental status in patients who sustained a severe traumatic
brain injury, according to coma duration in acute and post-acute rehabilitation.
[Subjects and Methods] The study population comprised patients with levels of
consciousness ranging from 3 to 8 according to Glasgow Coma Scale score. The
patients were divided into 2 groups based on coma duration as follows: group 1,
those who were in a coma up to 1 week, and group 2, those who were in a coma for
more than 2 weeks. The recovery of the patients' motor function was evaluated
according to the Motor Assessment Scale and the recovery of mental status
according to the Mini-Mental State Examination. [Results] The evaluation of motor
and mental status recovery revealed that the patients who were in a coma up to 1
week recovered significantly better after physical therapy during the acute
rehabilitation than those who were in a coma for longer than 2 weeks.
[Conclusion] The recovery of motor and mental status of the patients in acute
rehabilitation was significantly better for those in a coma for a shorter period.
PMID- 27512264
TI - Influence of load and carrying method on gait, specifically pelvic movement.
AB - [Purpose] The purpose of this study was to examine how carrying methods and load
affects pelvic movement while walking. [Subjects and Methods] Sixteen healthy
subjects (age 20.68 +/- 1.95 years, height 167.56 +/- 8.46 cm, weight 60.25 +/-
9.37 kg) volunteered. The items carried included a hand bag, shoulder bag, cross
bag, and a back pack. The load weights were 0%, 5%, 10% and 15% of body weight. G
Walk was used to record and analyze pelvic movement while the participants walked
with different loads. [Results] In the case of hand bags and shoulder bags,
pelvic tilt increased along with weight. In particular, when compared with the
0%, 5% and 10% load conditions, the 15% load of a hand bag induced a significant
increase. Pelvic rotation showed a tendency to decrease as the weight increased.
[Conclusion] Lateral pelvic tilt is thought to increase when the weight exceeds
15% of body weight, thereby resulting in decreased efficiency of gait. The pelvic
rotation is thought to decrease as the weight increases, causing restricted upper
limb movements.
PMID- 27512265
TI - Autonomic cardiovascular control recovery in quadriplegics after handcycle
training.
AB - The aim of this study was to investigate the cardiovascular autonomic acute
response, during recovery after handcycle training, in quadriplegics with spinal
cord injury (SCI). [Subjects and Methods] Seven quadriplegics (SCIG -level C6-C7,
male, age 28.00 +/- 6.97 years) and eight healthy subjects (CG -male, age 25.00
+/- 7.38 years) were studied. Their heart rate variability (HRV) was assessed
before and after one handcycle training. [Results] After the training, the SCIG
showed significantly reduced: intervals between R waves of the electrocardiogram
(RR), standard deviation of the NN intervals (SDNN), square root of the mean
squares differences of sucessive NN intervals (rMSSD), low frequency power (LF),
high frequency power (HF), and Poincare plot (standard deviation of short-term
HRV -SD1 and standard deviation of long-term HRV -SD2). The SDNN, LF, and SD2
remained decreased during the recovery time. The CG showed significantly reduced:
RR, rMSSD, number of pairs of adjacent NN intervals differing by more than 50 ms
(pNN50), LF, HF, SD1, and sample entropy (SampEn). Among these parameters, only
RR remained decreased during recovery time. Comparisons of the means of HRV
parameters evaluated between the CG and SCIG showed that the SCIG had
significantly lower pNN50, LF, HF, and SampEn before training, while immediately
after training, the SCIG had significantly lower SDNN, LF, HF, and SD2. The
rMSSD30s of the SCIG significantly reduced in the windows 180 and 330 seconds and
between the windows 300 seconds in the CG. [Conclusion] There was a reduction of
sympathetic and parasympathetic activity in the recovery period after the
training in both groups; however, the CG showed a higher HRV. The parasympathetic
activity also gradually increased after training, and in the SCIG, this activity
remained reduced even at three minutes after the end of training, which suggests
a deficiency in parasympathetic reactivation in quadriplegics after SCI.
PMID- 27512266
TI - Effect of the Masako maneuver and neuromuscular electrical stimulation on the
improvement of swallowing function in patients with dysphagia caused by stroke.
AB - [Purpose] The aim of this study was to compare improvements in swallowing
function by the intervention of the Masako maneuver and neuromuscular electrical
stimulation in patients with dysphagia caused by stroke. [Subjects and Methods]
The Masako maneuver (n=23) and neuromuscular electrical stimulation (n=24) were
conducted in 47 patients with dysphagia caused by stroke over a period of 4
weeks. Swallowing recovery was recorded using the functional dysphagia scale
based on videofluoroscopic studies. [Results] Mean functional dysphagia scale
values for the Masako maneuver and neuromuscular electrical stimulation groups
decreased after the treatments. However, the pre-post functional dysphagia scale
values showed no statistically significant differences between the groups.
[Conclusion] The Masako maneuver and neuromuscular electrical stimulation each
showed significant effects on the improvement of swallowing function for the
patients with dysphagia caused by stroke, but no significant difference was
observed between the two treatment methods.
PMID- 27512267
TI - Prior swimming exercise favors muscle recovery in adult female rats after joint
immobilization.
AB - [Purpose] To evaluate the efficacy of pre-exercise on immobilization and
subsequent recovery of white gastrocnemius (WG) and soleus (SOL) muscles of
female rats. [Subjects and Methods] Thirty, 8-month-old, female Wistar rats were
randomly and evenly allocated to six groups: sedentary (S); immobilized sedentary
(IS); immobilized/rehabilitated sedentary (IRS); trained (T); immobilized trained
(IT); and immobilized/rehabilitated trained (IRT). For four months, T, IT and IRT
group animals performed swimming exercise (three sessions per week, 60 minutes
per session), while S, IS and IRS groups animals remained housed in cages. After
this period, the left hindlimb of the animals from the IS, IRS, IT and IRT groups
was immobilized for five days, with the ankle at 90 degrees . After removal of
the orthosis, animals from the IRS and IRT groups followed a rehabilitation
program based on swimming (five sessions per week, 60 minutes per session) for
two weeks. [Results] Immobilization significantly reduced the cross-sectional
area of the white gastrocnemius muscle; no changes were observed in the soleus
muscles of the trained animals. Transforming growth factor-beta1 protein levels
were similar among the trained groups. [Conclusion] Prior swimming prevents
hypotrophy of the soleus muscle after immobilization, and protein levels
reflected the adaptive capacity of the skeletal muscle.
PMID- 27512268
TI - Treatment of trochanteric bursitis: our experience.
AB - [Purpose] Trochanteric bursitis is a disease for which there are no effective
standardized therapy protocols. Very often pain persists in spite of applying all
therapeutic treatments. The purpose of this study was to determine whether
treatment of trochanteric bursitis with a local injection of bicomponent
corticosteroid and 2% lidocaine would improve patients' conditions and relieve
pain symptoms in the trochanteric area. [Subjects and Methods] A retrospective
observational study was conducted of 2,217 patients in a 6 year follow-up period
at the Special Hospital "Agens", Mataruska Banja, Serbia. [Results] Of 2,217
examined patients, 58 (2.6%) patients were found to suffer from trochanteritis
associated with low back pain, and 157 (7%) were found to suffer from
trochanteric pains without low back pains. Local corticosteroid therapy followed
by physical therapy was effective in 77 (49%) of these patients, and only
corticosteroid injection in 61 (39%) patients. A single injection was given to 47
(29.9%) of the patients. Two injections were given to 9 (5.7%) patients, and from
3 to 5 injections were given repeatedly every 4-6 weeks to 7 (4.5%) patients.
[Conclusion] For most patients, local injections of corticosteroids with
lidocaine alone or followed by physical therapy gave satisfactory results.
PMID- 27512269
TI - Intra-rater reliability when using a tympanic thermometer under different self
measurement conditions.
AB - [Purpose] This study investigated intra-rater reliability when using a tympanic
thermometer under different self-measurement conditions. [Subjects and Methods]
Ten males participated. Intra-rater reliability was assessed by comparing the
values under three conditions of measurement using a tympanic thermometer.
Intraclass correlation coefficients were used to assess intra-rater reliability.
[Results] According to the intraclass correlation coefficient analysis,
reliability could be ranked according to the conditions of measurement.
[Conclusion] The results showed that self-measurement of body temperature is more
precise when combined with common sense and basic education about the anatomy of
the eardrum.
PMID- 27512270
TI - Immediate effects of neuromuscular joint facilitation intervention after anterior
cruciate ligament reconstruction.
AB - [Purpose] The aim of this study was to examine the immediate effects of
neuromuscular joint facilitation (NJF) on the functional activity level after
rehabilitation of anterior cruciate ligament (ACL) reconstruction. [Subjects and
Methods] Ten young subjects (8 males and 2 females) who underwent ACL
reconstruction were included in the study. The subjects were divided into two
groups, namely, knee joint extension muscle strength training (MST) group and
knee joint extension outside rotation pattern of NJF group. Extension strength
was measured in both groups before and after the experiment. Surface
electromyography (sEMG) of the vastus medialis and vastus lateralis muscles and
joint position error (JPE) test of the knee joint were also conducted. [Results]
JPE test results and extension strength measurements in the NJF group were
improved compared with those in the MST group. Moreover, the average discharge of
the vastus medialis and vastus lateralis muscles on sEMG in the NJF group was
significantly increased after MST and NJF treatments. [Conclusion] The obtained
results suggest that NJF training in patients with ACL reconstruction can improve
knee proprioception ability and muscle strength.
PMID- 27512271
TI - Effects of 12 weeks combined aerobic and resistance exercise on heart rate
variability in type 2 diabetes mellitus patients.
AB - [Purpose] This study evaluated the effects of 12 weeks combined aerobic and
resistance exercise on heart rate variability in patients with Type 2 diabetes
mellitus. [Subjects and Methods] The subjects were 16 female patients with Type 2
diabetes mellitus selected among the participants of a chronic disease management
exercise class at C Region Public Health Center in South Korea. Subjects were
randomly assigned to the exercise group (n=8; age, 55.97 +/- 7.37) or the control
group (n=8; age, 57.53 +/- 4.63) The exercise group performed aerobic and
resistance exercises for 60 minutes per day, 3 times per week for 12 weeks.
Anthropometric measurements, biochemical markers, physical fitness, and heart
rate variability were examined. [Results] After 12 weeks of exercise, weight,
body fat percentage, waist circumference, blood glucose, insulin resistance,
glycated hemoglobin level, systolic blood pressure, and diastolic blood pressure
significantly decreased and cardiorespiratory fitness and muscular strength
significantly increased in the exercise group. Although heart rate variability
measures showed favorable changes with the exercise program, none were
significant. [Conclusion] Although the exercise program did not show notable
changes in heart rate variability in patients with Type 2 diabetes within the
timeframe of the study, exercise may contribute to the prevention and control of
cardiovascular autonomic neuropathy.
PMID- 27512272
TI - Differences in performance on the functional movement screen between chronic low
back pain patients and healthy control subjects.
AB - [Purpose] Differences in scores on the Functional Movement Screen between
patients with chronic lower back pain and healthy control subjects were
investigated. [Subjects and Methods] In all, 20 chronic lower back pain patients
and 20 healthy control subjects were recruited. Chronic lower back pain patients
and healthy controls performed the Functional Movement Screen (deep squat, hurdle
step, inline lunge, shoulder mobility, active straight leg raise, trunk stability
pushup, and rotary stability). The Mann-Whitney test was used to analyze
differences in Functional Movement Screen scores between the two groups.
[Results] Chronic lower back pain patients scored lower on the Functional
Movement Screen total composite compared with healthy control subjects. Chronic
lower back pain patients scored lower on Functional Movement Screen subtests
including the deep squat, hurdle step, active straight leg raise, and rotary
stability tests. [Conclusion] The deep squat, hurdle step, active straight leg
raise, and rotary stability tasks of the Functional Movement Screen can be
recommended as a functional assessment tools to identify functional deficits in
chronic lower back pain patients.
PMID- 27512273
TI - Effect of respiratory warm-up on anaerobic power.
AB - [Purpose] The aim of the present study was to examine the effects of respiratory
muscle warm-up on anaerobic power. [Subjects and Methods] Thirty male field
hockey players (age, 20.5 +/- 2.0 years) each participated in a control (CAN)
trial and an experimental (EAN) trial. The EAN trial involved respiratory muscle
warm-up, while the CAN trial did not. Anaerobic power was measured using the
Wingate protocol. Paired sample t-tests were used to compare the EAN and CAN
trials. [Results] There were significant increases in peak power and relative
peak power, and decreases in the time to peak after the EAN trial by 8.9%, 9.6%,
and 28.8% respectively. [Conclusion] Respiratory muscle warm-up may positively
affect anaerobic power due to faster attainment of peak power.
PMID- 27512274
TI - The immediate effects of keyboard-based music therapy on probe reaction time.
AB - [Purpose] This study examined the immediate effects of keyboard-based music
therapy on Probe Reaction Time. [Subjects and Methods] Probe Reaction Time was
determined in 10 subjects by self-evaluation before and after music therapy
intervention. The Probe Reaction Time was separately measured 4 times. [Results]
After completion of music therapy intervention, the Probe Reaction Time in the 10
subjects was significantly decreased. [Conclusion] The results suggest that
keyboard-based music therapy is an effective and novel treatment, and should be
applied in clinical practice.
PMID- 27512275
TI - The effects of exercising on an unstable surface on the gait and balance ability
of normal adults.
AB - [Purpose] This study aimed to examine that therapeutic efficacy of an unstable
surface on balance and gait ability in normal individuals. [Subjects and Methods]
Forty subjects participated in the experiment and were randomly assigned to an
experimental group of 20 subjects and a control group of 20 subjects. The
experimental group performed balance exercise on an Aero-Step device (Aero-Step
XL, TOGU, Prien-Bachham, Germany). The control group performed balance exercise
on rigid ground. All subjects performed balance training 30 minutes a day, 5 days
a week, for 4 weeks. After the intervention, balance measuring equipment (Good
Balance, Metitur, Jyvaskyla, Finland) was used to quantitatively measure balance
ability. [Results] Significant differences in post-training gains in the
variables of static balance, dynamic balance, and velocity were observed between
the experimental group and the control group. [Conclusion] Unstable surface
training aimed at improving balance ability is considered to have a positive
effect.
PMID- 27512276
TI - Relationship of body composition, knee extensor strength, and standing balance to
lumbar bone mineral density in postmenopausal females.
AB - [Purpose] This study aimed to investigate correlations between lumbar bone
mineral density (BMD) and general characteristics of postmenopausal females,
including body composition, knee extensor strength, standing balance, and femur
BMD. [Subjects and Methods] A total of 40 postmenopausal females (55.6 +/- 4.6
years) who were caregivers or guardians of patients in the K hospital were
included in the study. The weight, height, body composition, left and right knee
extensor strength, standing balance, femur BMD, and lumbar BMD measurements of
the subjects were obtained. [Results] The effect of measurement variables on
lumbar BMD was examined. Increases in age and menopausal duration were observed
to significantly increase lumbar BMD, whereas an increase in height was found to
significantly decrease lumbar BMD. An increase in soft lean mass, skeletal muscle
mass, fat-free mass, and femur BMD was also associated with significantly
decreased lumbar BMD. [Conclusion] Age, menopausal duration, soft lean mass,
skeletal muscle mass, and fat-free mass were factors that decreased lumbar BMD in
menopausal females. This study is expected to provide basic knowledge for
osteoporosis prevention and treatment programs for postmenopausal females.
PMID- 27512277
TI - Cut-off point for the trail making test to predict unsafe driving after stroke.
AB - [Purpose] This study examined the cut-off point of the Trail Making Test in
predicting the risk of unsafe driving in stroke patients. [Subjects and Methods]
A total of 81 stroke patients with a driver's license participated in this study.
The DriveABLE Cognitive Assessment Tool, Trail Making Test-A, and Trail Making
Test-B evaluations were conducted in all participants. All participants were
classified into the safety or risk groups based on the DriveABLE Cognitive
Assessment Tool evaluation results. The Trail Making Test results underwent a
receiver operating characteristic analysis in each group. [Results] The results
of the receiver operating characteristic curve analysis showed that the cut-off
point for Trail Making Test-A was 32 seconds and the cut-off point for Trail
Making Test-B was 79 seconds. The positive predictive values of the Trail Making
Test-A and Trail Making Test-B were 98.3% and 98.3%, respectively, and the
negative predictive values of the Trail Making Test-A and Trail Making Test-B
were 81.0% and 73.9%, respectively. [Conclusion] The Trail Making Test is a
useful tool for predicting the risk of unsafe driving in stroke patients. This
tool is expected to be used more actively for screening stroke drivers with
respect to their cognitive function.
PMID- 27512278
TI - EMG activity of the serratus anterior and trapezius muscles during the different
phases of the push-up plus exercise on different support surfaces and different
hand positions.
AB - [Purpose] The appropriate exercise prescription is crucial for achieving scapular
stability and providing successful rehabilitation, and the Push-up Plus (PuP)
exercise has an important role in shoulder rehabilitation. Consequently, this
study examined the effect of support surface stability, hand positioning, and
phase of exercise, on the trapezius and serratus anterior muscle contractions as
well as on the EMG ratio of the upper/lower trapezius. [Subjects and Methods]
Thirteen healthy male volunteers participated in this study. The subjects
performed the PuP exercise on stable and unstable supporting surfaces with three
different hand orientations. During the PuP exercise, the muscle activities of
the upper (UT) and lower (LT) trapezius, as well as the serratus anterior (SA)
were measured and expressed as percentages of maximum voluntary isometric
contraction (%MVIC). [Results] The EMG activities of UT and LT were statistically
greater during the push-up phase compared to the plus phase of the exercise. The
contrary was recorded for the activity of the SA. SA was affected by the support
surface as well as by the hand positioning. [Conclusion] The results suggest that
different phases of the PuP exercise require different muscle stability actions
with corresponding activations of appropriate muscle fibers. A detailed
prescription of the required phase of the exercise can more effectively activate
the scapula-thoracic musculature.
PMID- 27512279
TI - The effect of co-stabilizer muscle activation on knee joint position sense: a
single group pre-post test.
AB - [Purpose] The purpose of this study was to investigate the effect of co
stabilizer muscle activation on knee joint position sense. [Subjects and Methods]
This study was a pre-post, single-blinded randomly controlled trial (angle
sequence randomly selected) design. Seven healthy adults with no orthopaedic or
neurological problems participated in this study. Knee joint position sense was
measured by a target matching test at target angles of 30 degrees , 45 degrees
and 80 degrees of knee flexion a using digital inclinometer under two
conditions: erect sitting, which is known to highly activate co-stabilizer muscle
and slump sitting, which is known to little activate the co-stabilizer muscle.
[Results] A significant difference in joint position matching error at the knee
flexion angle of 45 degrees was founded between two conditions erect sitting:
(3.83 +/- 1.47) and slump sitting: (1.00 +/- 0.63). There were no significant
differences in joint position matching error at the other target angles.
[Conclusion] Knee joint position sense at 45 degrees is likely to be affected by
activation of co-stabilizer muscle, and this value is suitable for facilitation
of joint position sense with skilled movement.
PMID- 27512280
TI - Validity and reliability of isometric muscle strength measurements of hip
abduction and abduction with external hip rotation in a bent-hip position using a
handheld dynamometer with a belt.
AB - [Purpose] This study aimed to investigate the relatedness, reliability, and
validity of isometric muscle strength measurements of hip abduction and abduction
with an external hip rotation in a bent-hip position using a handheld dynamometer
with a belt. [Subjects and Methods] Twenty healthy young adults, with a mean age
of 21.5 +/- 0.6 years were included. Isometric hip muscle strength in the
subjects' right legs was measured under two posture positions using two devices:
a handheld dynamometer with a belt and an isokinetic dynamometer. Reliability was
evaluated using an intra-class correlation coefficient (ICC); relatedness and
validity were evaluated using Pearson's product moment correlation coefficient.
Differences in measurements of devices were assessed by two-way ANOVA. [Results]
ICC (1, 1) was >=0.9; significant positive correlations in measurements were
found between the two devices under both conditions. No main effect was found
between the measurement values. [Conclusion] Our findings revealed that there was
relatedness, reliability, and validity of this method for isometric muscle
strength measurements using a handheld dynamometer with a belt.
PMID- 27512281
TI - Effects of concentric and eccentric control exercise on gross motor function and
balance ability of paretic leg in children with spastic hemiplegia.
AB - [Purpose] This study examines the effect of concentric and eccentric control
training of the paretic leg on balance and gross motor function in children with
spastic hemiplegia. [Subjects and Methods] Thirty children with spastic
hemiplegia were randomly divided into experimental and control groups. In the
experimental group, 20 min of neurodevelopmental therapy and 20 min of concentric
and eccentric control exercise were applied to the paretic leg. In the control
group, 40 min of neurodevelopmental therapy was applied. The Pediatric Balance
Scale test and standing and gait items of the Gross Motor Function Measure were
evaluated before and after intervention. [Results] In the experimental group,
Gross Motor Function Measure and Pediatric Balance Scale scores statistically
significantly increased after the intervention. The control group showed no
statistically significant difference in either score after the intervention.
[Conclusion] Concentric and eccentric control exercise therapy in children with
spastic hemiplegia can be effective in improving gross motor function and balance
ability, and can be used to solve functional problems in a paretic leg.
PMID- 27512282
TI - A study of the development of the Korean version of PedsQL(TM) 3.0 cerebral palsy
module and reliability and validity.
AB - [Purpose] The purpose of this study was to develop the Korean version of the
PedsQL(TM) 3.0 Cerebral Palsy Module to evaluate the health-related quality of
life of children with cerebral palsy and to test the reliability and validity.
[Subjects and Methods] The study included 108 caregivers of children with
cerebral palsy aged 2 to 4 years and 72 caregivers of children aged 5 to 7 years,
who visited multiple sites between February and August 2015. The Translation
Commission performed the first translation with the approval of the Mapi Research
Trust Company to create a Korean-version of the PedsQL(TM). Afterwards, back
translation was performed by one translator specializing in health and medical
treatment who was a native English-speaker fluent in Korean, and one native
Korean-speaker fluent in English. The consistency of each question was confirmed
and a translation-integrated version was created. Test components were explained
to caregivers during a one-on-one interview; caregivers then completed the
PedsQL(TM) questionnaire and a Pediatric Evaluation Disability Inventory (PEDI)
questionnaire. Subjects contributing to test-retest measures were asked to repeat
the PedsQL questionnaire one week later and return it by mail. To assess data
quality for the survey question results, non-response rate, ceiling effect, and
floor effect were analyzed. Test-retest reliability and internal consistency
reliability were assessed. For test-retest reliability, an intraclass correlation
coefficient (ICC) was calculated, and for internal consistency reliability,
Cronbach's alpha was used. To test criterion-related validity, Pearson's
correlation coefficient was used. [Results] The content validity of the PedsQL
3.0 Cerebral Palsy Module was high for both age groups, and demonstrated
significant internal consistency (>0.7) in all areas. For test-retest
reliability, both groups demonstrated a significant ICC (>0.61). Correlation with
the PEDI was statistically significant in all areas except pain and hurt.
[Conclusion] The Korean version of the PedsQL(TM) 3.0 Cerebral Palsy Module was
found to be reliable and valid, and is expected to contribute greatly to the
evaluation of the quality of life of children with cerebral palsy.
PMID- 27512283
TI - Clinical usefulness of the clock drawing test applying rasch analysis in
predicting of cognitive impairment.
AB - [Purpose] This study examined the clinical usefulness of the clock drawing test
applying Rasch analysis for predicting the level of cognitive impairment.
[Subjects and Methods] A total of 187 stroke patients with cognitive impairment
were enrolled in this study. The 187 patients were evaluated by the clock drawing
test developed through Rasch analysis along with the mini-mental state
examination of cognitive evaluation tool. An analysis of the variance was
performed to examine the significance of the mini-mental state examination and
the clock drawing test according to the general characteristics of the subjects.
Receiver operating characteristic analysis was performed to determine the cutoff
point for cognitive impairment and to calculate the sensitivity and specificity
values. [Results] The results of comparison of the clock drawing test with the
mini-mental state showed significant differences in according to gender, age,
education, and affected side. A total CDT of 10.5, which was selected as the
cutoff point to identify cognitive impairement, showed a sensitivity,
specificity, Youden index, positive predictive, and negative predicive values of
86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is
believed to be useful in assessments and interventions based on its excellent
ability to identify cognitive disorders.
PMID- 27512284
TI - The effects of trunk stabilization exercise using a Swiss ball in the absence of
visual stimulus on balance in the elderly.
AB - [Purpose] This study was undertaken to investigate the effects of the balance
exercises with a Swiss ball on static and dynamic balance abilities in elderly
(>=65 years) subjects. [Subjects and Methods] Twenty elderly subjects with no
relevant orthopedic history of a back condition were selected for trunk
stabilization exercises with a Swiss ball (Thera-Band, USA). The subjects
performed these trunk stabilization exercises for 20 minutes, five times per week
for 4 weeks. The experimental group (n=10) was blindfolded during these balance
exercises, while the control group control group (n=10) was not. [Results] The
experimental group showed significant improvements in velocity in the evaluation
of static balance and in time, total distance, and left/right movement distance
in the evaluation of dynamic balance after the intervention, whereas the control
group showed significant improvements in time in the evaluation of dynamic
balance. A significant intergroup difference was observed after the intervention
for velocity gain. [Conclusion] Exercising with a blindfold stimulates other
senses by blocking visual information, and hence it enhances improvements in
balance ability.
PMID- 27512285
TI - Comparison of spatiotemporal gait parameters with a spinal orthosis and without a
spinal orthosis on level ground and stairs.
AB - [Purpose] This study attempted to examine the impact on the pattern of walking on
both level ground and stairs after restricting the movement of the spine and the
trunk of the body by using a spinal orthosis. [Subjects and Methods] Forty
healthy males in their 20s were selected as the sample, which was randomly and
evenly divided into two groups: (1) the WT group (with a thoracolumbosacral
orthosis group) and (2) the WOT group (Without a thoracolumbosacral orthosis
group). The spinal orthosis used in this study was a thoracolumbosacral orthosis
called a plastic body jacket. [Results] In walking on level ground, step width
showed a significant difference, but no statistically significant difference was
found between the WT group and the WOT group with respect to the other variables.
In walking on stairs, the double stance phase showed a statistically significant
difference during stair descent in the WT group compared with the WOT group.
[Conclusion] It was proven that wearing a TLSO increased walking stability in the
case of walking on level ground and stairs. Hence, it is believed that proper use
of a spinal orthosis can play an ancillary role in daily life and therapeutic
interventions.
PMID- 27512286
TI - Effects of shoulder reaching exercise on the balance of patients with hemiplegia
after stroke.
AB - [Purpose] This study investigated whether a shoulder reaching exercise was
beneficial for restoring the standing balance of patients with hemiplegia after
stroke. [Subjects and Methods] There were 13 subjects in the experimental group
(EG) and 14 subjects in the control group (CG), all with hemiplegia following
stroke. The shoulder reaching exercise intervention was performed by the EG and
conventional physical therapy was administered to the CG for 30 minutes, 3 times
a week for 4 weeks. Virtual reality (RM, BioRescue -AP 1153, France) was used as
an assessment tool. All data were analyzed using SPSS version 18 (Statistical
Package for the Social Science). [Results] After the intervention, the EG showed
significant differences in the distances moved in the anteroposterior and
mediolateral directions. The length and velocity were reduced after the
intervention in both the EG and the CG. There were significant differences in the
distances moved in the north, south and west directions between the groups. The
sway path lengths of the subjects in the Romberg test were reduced under both the
eyes open and closed conditions in the EG. There was no significant variation in
sway velocity in the EG and the CG. [Conclusion] The shoulder reaching exercise
had beneficial effects on the distances moved in the anteroposterior and
mediolateral directions.
PMID- 27512287
TI - Effects of neurofeedback and computer-assisted cognitive rehabilitation on
relative brain wave ratios and activities of daily living of stroke patients: a
randomized control trial.
AB - [Purpose] This study investigated the effects of neurofeedback (NFB) and computer
assisted cognitive rehabilitation (CACR) on the relative brain wave ratios and
activities of daily living (ADL) of stroke patients. [Subjects and Methods] Forty
four participants were randomly allocated to the NFB (n=14), CACR (n=14), or
control (CON) (n=16) groups. Two expert therapists provided the NFB, CACR, and
CON groups with traditional rehabilitation therapy in 30-minute sessions, 5 times
a week, for 6 weeks. NFB training was provided only to the NFB group and CACR
training was provided only to the CACR group. The CON group received traditional
rehabilitation therapy only. Before and after 6 weeks of intervention, brain wave
and ADL evaluations were performed, and the results were analyzed. [Results] The
relative ratio of beta waves, only showed a significant increase in the frontal
and parietal areas of the NFB group. Significant changes in ADL were shown by all
three groups after the intervention. However, there were no significant
differences between the NFB and CACR groups and the CON group. [Conclusion] Our
results suggest that CACR and NFB are effective at improving cognitive function
and ADL of stroke patients.
PMID- 27512288
TI - The association of vitamin D with inflammatory cytokines in diabetic peripheral
neuropathy.
AB - [Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13
were investigated in patients with diabetic peripheral neuropathy, patients with
diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and
Methods] A single-blind controlled clinical study was performed, including70 type
2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy
volunteer controls. The 25(OH)D levels were evaluated using ultra-performance
liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme
linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was
lower in diabetic peripheral neuropathy patients than in diabetes mellitus
patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were
lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels
were higher in diabetes mellitus patients than in controls. Additionally, IL-13
levels were higher in diabetic peripheral neuropathy patients than in diabetes
mellitus patients without neuropathy. These differences were statistically
significant. There was a significant positive correlation between 25(OH)D and IL
13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and
diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk
factor for diabetic peripheral neuropathy and may regulate inflammatory
mediators, e.g., IL-17 and IL-13.
PMID- 27512289
TI - A systematic review of sleep disorders in patients with chronic kidney disease
undergoing hemodialysis.
AB - The purpose of this study was to conduct a systematic review of the available
evidence on sleep disorders in patients with end stage renal disease (ESRD)
undergoing hemodialysis (HD). [Subjects and Methods] Two independent reviewers
performed a computer-assisted search of the MEDLINE, SciELO, LILACS, and BIREME
Virtual Health Library medical databases from their inception to November 2015.
[Results] One thousand one hundred twenty-six articles were found that met the
inclusion criteria. Articles were excluded if they were not in English, the
patients did not undergo HD, or the studies were not cross-sectional or clinical
trials. After reading the full text, a further 300 studies were excluded because
they did not use polysomnography. The remaining 18 studies with ESRD patients
undergoing HD comprised 8 clinical trials and 10 cross-sectional studies. This
systematic review followed the criteria outlined by the PRISMA declaration.
[Conclusion] In this systematic review, a high prevalence of sleep disorders was
observed in ESRD, including sleep-disordered breathing. This knowledge may enable
health professionals to devise new strategies for the diagnosis and treatment of
these patients, in order to reduce morbidity and mortality and improve their
quality of life.
PMID- 27512290
TI - Effects of yoga on chronic neck pain: a systematic review of randomized
controlled trials.
AB - [Purpose] The aim of this study was to investigate the effectiveness of yoga in
the management of chronic neck pain. [Subjects and Methods] Five electronic
databases were searched to identify randomized controlled trials (RCTs) of yoga
intervention on chronic neck pain. The trials were published in the English
language between January 1966 and December 2015. The Cochrane Risk of Bias Tool
was used to assess the quality of the trials. [Results] Three trials were
identified and included in this review. A critical appraisal was performed on the
trials, and the result indicated a high risk of bias. A narrative description was
processed because of the small number of RCTs. Neck pain intensity and functional
disability were significantly lower in the yoga groups than in the control
groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that
yoga may be beneficial for chronic neck pain. The low-quality result of the
critical appraisal and the small number of trials suggest that high-quality RCTs
are required to examine further the effects of yoga intervention on chronic neck
pain relief.
PMID- 27512291
TI - Effect of pain scrambler therapy on shoulder joint pain and range of motion in
patients who had undergone arthroscopic rotator cuff repair for the first time.
AB - [Purpose] This study aimed to determine the effect of pain scrambler therapy on
shoulder joint pain and range of motion in patients who had undergone
arthroscopic rotator cuff repair for the first time. [Subjects and Methods] Pain
scrambler therapy was administered once a day every 40 minutes for 10 days to
patients that had undergone arthroscopic rotator cuff repair for the first time.
The visual analog scale was used to measure pain, and a goniometer was used to
measure shoulder range of motion. [Results] After 10 sessions of pain scrambler
therapy, pain was significantly reduced from that before the treatment. In
addition, shoulder range of motion was increased after 10 treatment sessions.
[Conclusion] Thus, pain scrambler therapy greatly reduced pain and increased
should range of motion in the patients who had undergone arthroscopic rotator
cuff repair for the first time.
PMID- 27512292
TI - Integer programming models and branch-and-cut approaches to generalized {0,1,2}
survivable network design problems.
AB - In this article, we introduce the Generalized [Formula: see text]-Survivable
Network Design Problem ([Formula: see text]-GSNDP) which has applications in the
design of backbone networks. Different mixed integer linear programming
formulations are derived by combining previous results obtained for the related
[Formula: see text]-GSNDP and Generalized Network Design Problems. An extensive
computational study comparing the correspondingly developed branch-and-cut
approaches shows clear advantages for two particular variants. Additional
insights into individual advantages and disadvantages of the developed algorithms
for different instance characteristics are given.
PMID- 27512294
TI - Effect of low dose nicotinic acid on hyperphosphatemia in patients with end stage
renal disease.
AB - Hyperphosphatemia is a risk factor for ectopic calcification and coronary artery
diseases in end stage renal diseases (ESRD). The aim of this study was to assess
the effect of low-dose nicotinic acid on hyperphosphatemia in patients with ESRD.
This randomized, double-blind clinical trial was done on 70 ESRD patients with
serum phosphoure >=5.5 mg/dl. Patients were randomly divided into two equal
groups (n = 35) and the intervention group received niacin 25 mg/day as the
initial dose. After 4 weeks, in patients who did not respond to treatment, niacin
dose was increased up to 50 mg/dl. At the end of week 8, in case there was no
treatment effect, the dose was raised to 100 mg/day. The appropriate response to
treatment was defined as serum phosphorous level reductions <5.5 mg/dl. The age
was 50.5 +/- 14.3 years and duration of dialysis 5.1 +/- 5.3 months. In the
niacin group, mean phosphorus level decreased from 6.7 +/- 0.84 mg/dl at the end
of the 1(st) month to 5.8 +/- 1.0 mg/dl at the end of the 2(nd) month and to 4.4
+/- 1.4 mg/dl at the end of the 3(rd) month (P = 0.004). In the placebo group,
mean phosphorus level increased from 6.5 +/- 1.2 mg/dl to 7.2 +/- 0.91 mg/dl at
the end of the 3(rd) month (P = 0.006). In the niacin group, high density
lipoprotein (HDL) increased significantly from 45.00 +/- 14.9 to 47.2 +/- 11.6 (P
= 0.009). We conclude that niacin (100 mg/day) decreased phosphorus serum level
and increased HDL serum level in patients on dialysis.
PMID- 27512293
TI - Negative pressure wound therapy induces early wound healing by increased and
accelerated expression of vascular endothelial growth factor receptors.
AB - BACKGROUND: Negative pressure wound therapy (NPWT) is commonly used to accelerate
wound healing, especially following thoracic surgery; however, the mechanism
remains elusive. Given the important role of vasculogenesis in wound healing, we
evaluated whether NPWT might accelerate vasculogenesis in the wound area. Toward
this end, we investigated the temporal expression of vascular endothelial growth
factor receptors (VEGFRs) in an NPWT-wound healing rabbit model. METHODS: Rabbits
were divided into an NPWT group and a non-NPWT control group, and tissue samples
were collected around wounds made in the skin of each rabbit at five time points:
0, 7, 14, 21, and 28 days after wound creation. Cryopreserved samples were then
immunostained and subject to image analysis to evaluate the temporal changes in
VEGFR1, VEGFR2, and VEGFR3 expression in the wound-healing process. RESULTS:
Results of histological analysis of the temporal changes in VEGFR expression
throughout the healing process showed that compared to the control group, VEGFR2
and VEGFR3 were abundantly and rapidly expressed in the NPWT group, and were
expressed earlier than VEGFR1. CONCLUSIONS: NPWT promotes the expression of
VEGFR2 and VEGFR3, which provides insight into the mechanism by which NPWT
accelerates wound healing. Level of Evidence: Not ratable.
PMID- 27512295
TI - Pegylated interferon monotherapy for hepatitis C virus infection in patients on
hemodialysis: A single center study.
AB - There is no published study from India on hepatitis C virus (HCV) treatment in
dialysis patients. Patients on dialysis with HCV infection treated with pegylated
interferon (Peg-INF) monotherapy were studied. All patients were subjected to HCV
polymerase chain reaction, viral load, genotype, and liver biopsy. Quantitative
HCV-RNA was performed monthly. Patients with genotype 1 and 4 were given 12 month
therapy while those with genotypes 2 and 3 were given 6 months therapy. Response
was classified as per standard criteria of rapid virological response (RVR),
early virological response (EVR), end of treatment response (ETR), and sustained
virological response (SVR). A total of 85 patients were treated. Mean age was
35.2 +/- 10.5 (range 15-67) years, and 77.6% were males. HCV genotypes were 1 in
40.9%, 2 in 12%, 3 in 36.1%, 4 in 3.6%, and others in 7.2%. Mean viral load was
10(6) copies/mL. Mean liver biopsy grade was 4 +/- 1.7 and stage 0.8 +/- 0.8.
Mean time from diagnosis of HCV infection and the treatment start was 10.7 +/-
14.3 months. One patient died of unrelated illness, one was lost to follow-up,
and three could not sustain treatment due to cost. Forty-three of the 80 (54%)
patients had RVR while 49 (61%) patients had EVR and ETR. There was no difference
in term of RVR related to genotype. Fifty -four percentage had SVR. Mild flu-like
symptoms were seen in all patients. Sixty-four (80%) patients required increase
in erythropoietin doses. Twenty-eight (35%) patients developed leukopenia (three
treatment-limiting) and 16 (20%) developed thrombocytopenia (one treatment
limiting). Five patients developed tuberculosis, five bacterial pneumonia, and
one bacterial knee monoarthritis. None of the patients developed depression. Our
study concludes that Peg-INF monotherapy resulted in 54% RVR and SVR in dialysis
patients with HCV infection. Therapy was well-tolerated with minimal side
effects. There was no effect of viral genotype on response to therapy.
PMID- 27512296
TI - Clinical spectrum and outcomes of crescentic glomerulonephritis: A single center
experience.
AB - There is limited data on the etiology, clinical and histopathological spectrum
and outcomes of crescentic glomerulonephritis (CrGN) in adult Indian population.
This prospective study was done to evaluate the etiology, clinicohistological
patterns and predictors of outcome of CrGN in South Indian population. All the
patients received standard protocol based immunosuppression in addition to
supportive care. Immune-complex glomerulonephritis (ICGN) was the most common
etiology (n = 31; 77.5%) followed by pauci-immune glomerulonephritis (PauciGN; n
= 8; 20%) and anti-glomerular basement membrane disease (n = 1; 2.5%). The most
common etiology of ICGN was IgA nephropathy (n = 11; 27.5%) followed by lupus
nephritis (n = 7; 17.5%) and post-infectious glomerulonephritis (PIGN) (n = 7;
17.5%). The patients with PauciGN were significantly older compared to those with
ICGN (44.5 +/- 15 years vs. 31.8 +/- 11 years; P = 0.01). The patients with
PauciGN presented with significantly higher serum creatinine (9.7 +/- 4.4 vs. 6.6
+/- 3.3 mg/dl; P = 0.03). The histopathologic parameters of ICGN and PauciGN were
comparable except for a higher proportion of sclerosed glomeruli in ICGN. At the
end of 3 months follow-up, only two patients went into complete remission (5.4%).
Majority of the patients had end-stage renal failure (48.6%) and were dialysis
dependent and seven patients (18.9%) expired. There was no signifi difference in
the renal survival (10.9 +/- 1.9 vs. 9.6 +/- 3.3 months) or patient survival
(17.5 +/- 2.1 vs. 17.3 +/- 4.3 months). The parameters associated with adverse
outcomes at 3 months were hypertension (odds ratio [OR]: 0.58; confidence
interval [CI]: 0.36-0.94), need for renal replacement therapy (OR: 0.19; CI: 0.04
0.9), serum creatinine at admission (P = 0.019), estimated glomerular filtration
rate (P = 0.022) and percentage of fibrocellular crescents (P = 0.022).
PMID- 27512297
TI - Prevalence of serum anti M-type phospholipase A2 receptor antibody in primary
membranous nephropathy: A single center experience.
AB - We conducted a prospective study to assess utility of detection of antibodies to
phospholipase A2receptor (PLA2R) in the serum of patients with membranous
nephropathy. Seventy five patients with biopsy proven membranous nephropathy
admitted between January 2011 and September 2014 were studied. Serum anti- PLA2R
was tested by indirect immunofluorescence. The test was positive in 45 out of 60
patients with primary membranous nephropathy (PMN) and in none of the 15 patients
with secondary membranous nephropathy, with a sensitivity of 75% and specificity
of 100% for PMN. Anti PLA2R positivity also showed a significant correlation with
quantum of proteinuria and negative correlation with serum albumin. This study
has validated detection of serum anti PLA2R in PMN as a non invasive diagnostic
tool in Indian patients.
PMID- 27512298
TI - Changing picture of acute kidney injury in pregnancy: Study of 259 cases over a
period of 33 years.
AB - The incidence of acute kidney injury (AKI) in pregnancy is declining in
developing countries but still remains a major cause of maternal and fetal
morbidity and mortality. The aim of the study was to analyze the changing trends
in pregnancy related AKI (PR-AKI) over a period of thirty-three years. Clinical
characteristics of PR-AKI with respect to incidence, etiology and fetal and
maternal outcomes were compared in three study periods, namely 1982-1991,1992
2002 and 2003-2014. The incidence of PR-AKI decreased to 10.4% in 1992-2002, from
15.2% in 1982-1991, with declining trend continuing in 2003-2014
(4.68%).Postabortal AKI decreased to 1.49% in 2003-2014 from 9.4% in 1982-1991of
total AKI cases. The AKI related to puerperal sepsis increased to 1.56% of all
AKI cases in 2003-2014 from 1.4% in 1982-1991. Preeclampsia/eclampsia associated
AKI decreased from 3.5% of total AKI cases in 1982-1991 to 0.54% in 2003-2014.
Pregnancy associated - thrombotic microangiopathy and acute fatty liver of
pregnancy were uncommon causes of AKI. Hyperemesis gravidarum associated AKI was
not observed in our study. Incidence of renal cortical necrosis (RCN) decreased
to 1.4% in 2003-2014 from 17% in 1982-1991.Maternal mortality reduced to 5.79%
from initial high value 20% in 1982-1991. The progression of PR-AKI to ESRD
decreased to1.4% in 2003-2014 from 6.15% in 1982-1991. The incidence of PR-AKI
has decreased over last three decades, mainly due to decrease in incidence of
postabortal AKI. Puerperal sepsis and obstetric hemorrhage were the major causes
of PR-AKI followed by preeclampsia in late pregnancy. Maternal mortality and
incidence and severity of RCN have significantly decreased in PR-AKI. The
progression to CKD and ESRD has decreased in women with AKI in pregnancy in
recent decade. However, the perinatal mortality did not change throughout study
period.
PMID- 27512299
TI - Comparison of outcomes between surgically placed and percutaneously placed
peritoneal dialysis catheters: A retrospective study.
AB - There is lack of adequate data on comparison of outcomes between percutaneously
placed peritoneal dialysis (PD) catheters inserted by nephrologists and PD
catheters placed by surgeons. The aim of this study is to retrospectively analyze
the outcomes of PD catheters inserted by surgeons (by open surgical or
laparoscopic technique) and compare them with those inserted by nephrologists
among ESRD patients who underwent elective PD catheter insertions between January
2009 and December 2012. The primary outcome measure was the proportion of
catheters removed because of primary nonfunction. The secondary outcome measures
were catheter survival, patient survival, and incidence of complications of
catheter insertion. A total of 143 PD catheter insertions (88 by surgeons and 55
by nephrologists) performed in 132 patients were considered for the analysis. The
primary nonfunction rate of PD catheter insertions in both groups was comparable
(18.2% and 7.3%, P = 0.08). Break-in period was shorter in Group N (p = <0.001).
No differences were noted in patient or catheter survival. Percutaneously placed
PD catheters performed by nephrologists have comparable outcomes with surgically
placed PD catheters among selected cases and have the advantage of lower costs,
avoidance of operation theater scheduling issues, smaller incision length, and
shorter break-in period. Therefore, more nephrologists should acquire the
expertise on percutaneous PD catheter placement as it leads to lesser waiting
times and better utilization of PD.
PMID- 27512300
TI - Association of chemokine receptor CX3CR1 V249I and T280M polymorphisms with
chronic kidney disease.
AB - The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 are involved in the
activation of leukocytes. Two common single-nucleotide polymorphisms of the
CX3CR1 gene, V249I and T280M, have been associated with reduced fractalkine
signaling, leading to decreased adhesive function and leukocyte chemotaxis. We
hypothesized that variation in the CX3CR1 gene could be associated with chronic
kidney disease (CKD), a disease of inflammatory activation. We studied the
association between CX3CR1 V249I and T280M polymorphisms, and fractalkine and
highly sensitive C-reactive protein (hs-CRP) levels in 123 patients with CKD and
100 healthy controls (HCs). Genotype analysis was done by polymerase chain
reaction-restriction fragment length polymorphism, and fractalkine and hs-CRP
levels were analyzed by enzyme-linked immunosorbent assay. MM genotype of T280M
was absent in CKD patients, while in controls it was seen in 1% of the
individuals. The allele frequencies in both the groups were similar (P = 0.059).
Compared to HC, M280M + T280M genotype was more frequent in CKD (P = 0.041). The
frequency of II genotype of V249I was 0.8% in CKD, whereas in HC, it was 2%.
I249I + V249I genotype was more frequent in CKD as compared to HC (P = 0.034). No
difference in allelic frequency of V249I was noted between the two groups (P =
0.061, odds ratios = 1.74, 95% confidence intervals = 0.96-3.12). Plasma
fractalkine and serum hs-CRP levels were higher in CKD subjects (P = 0.004 and P
< 0.0001). No association of either genotype was found with fractalkine and hs
CRP levels. Polymorphisms at I249 and M280 genotype in CX3CR1 gene are associated
with CKD; however, there was no association of fractalkine or inflammatory marker
with these genotypes.
PMID- 27512301
TI - Epstein-Barr virus-positive multiple myeloma following an ABO incompatible second
renal transplantation.
AB - ABO incompatible kidney transplant recipients receive higher dose of
immunosuppression. Previous data indicate that the incidence of malignancy is not
higher in these patients. Compared to the general population, renal transplant
recipients are at 4.4-fold higher risk of developing myeloma. We describe a case
of posttransplant multiple myeloma in an ABO incompatible renal transplant
recipient of a second graft.
PMID- 27512302
TI - Lupus podocytopathy: An important differential diagnosis of nephrotic syndrome in
systemic lupus erythematosus.
AB - Some patients with systemic lupus erythematosus (SLE) present with sudden onset
of nephrotic syndrome and biopsy findings may be of minimal change disease or
focal segmental glomerulosclerosis with diffuse foot process effacement on
electron microscopy but without significant immune deposits. This entity is
termed lupus podocytopathy. Clinicians and renal pathologists need to be aware of
this condition. Though steroid sensitive, it needs follow-up to recognize flare
and class change, thereby optimizing therapy.
PMID- 27512303
TI - Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two
South Indian families with primary hyperoxaluria type 1 causing later onset end
stage kidney disease.
AB - Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism
due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase
deficiency. Here, we describe two unrelated patients who were diagnosed to have
primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript
ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation
was detected in both the patients and the parents were found to be heterozygous
carriers. Our patients developed end-stage renal disease at 23 years and 35 years
of age. However, in the largest series published from OxalEurope cohort, the
median age of end-stage renal disease for null mutations carriers was 9.9 years,
which is much earlier than our cases. Our patients had slower progressions as
compared to three unrelated patients from North India and Pakistan, who had
homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further,
patients need to be studied to find out if c.445_452delGTGCTGCT mutation
represents a founder mutation in Southern India.
PMID- 27512304
TI - Collapsing glomerulopathy associated with hepatitis B infection: A case report.
AB - Collapsing glomerulopathy has been classified as a variant of focal segmental
glomerulosclerosis. It is associated with infections, inflammations, and certain
medications. While its association with human immunodeficiency virus has been
well established its occurrence with hepatitis B has not been reported. We
present here a case of collapsing glomerulopathy in a child with hepatitis B
infection.
PMID- 27512305
TI - Karyomegalic interstitial nephropathy following ifosfamide therapy.
AB - Ifosfamide (IFO), an alkylating agent used for the management of solid organ
tumors, can cause reversible Fanconi's syndrome and acute kidney injury.
Karyomegalic interstitial nephropathy (KIN) is a rare form of chronic
tubulointerstitial nephritis, initially described as a familial nephropathy in
adults. So far, four cases of KIN have been reported in pediatric and adolescent
population following treatment with IFO. We report a 22-year-old man who
developed renal dysfunction following IFO therapy for relapsed Hodgkin's
lymphoma. Renal biopsy revealed chronic tubulointerstitial nephritis with
atypical tubular epithelial cells showing nuclear enlargement and hyperchromasia,
consistent with a diagnosis of KIN. The renal function improved following a short
course of corticosteroids.
PMID- 27512306
TI - Lymphoblastic lymphoma presenting as bilateral renal enlargement diagnosed by
percutaneous kidney biopsy: Report of three cases.
AB - Renal involvement by lymphoma can be a diagnostic challenge. Acute kidney injury
(AKI) is an unusual manifestation of lymphomatous infiltration in the kidneys. We
report three cases of lymphoblastic lymphoma, a very rare form of lymphoma,
presenting with AKI and bilateral enlargement of kidneys, diagnosed by
percutaneous kidney biopsy. Lymphomatous infiltration should be suspected with
such clinical presentation. Kidney biopsy is a valuable diagnostic tool, to
establish the correct diagnosis and subtype of lymphoma for timely initiation of
therapy for these aggressive hematological malignancies.
PMID- 27512307
TI - Microfilaria associated macroscopic hematuria and nephrotic range proteinuria.
PMID- 27512308
TI - Acquired perforating dermatosis in a diabetic patient on hemodialysis.
PMID- 27512309
TI - Spontaneous reno-colic fistula in an elderly patient.
PMID- 27512310
TI - Collapsing focal segmental glomerulosclerosis in a patient with systemic lupus
erythematosus.
PMID- 27512311
TI - An unusual cause of lower limb ulcer in renal allograft recipient.
PMID- 27512312
TI - Bilateral renal cortical necrosis in a patient undergoing in vitro fertilization.
PMID- 27512313
TI - Membranous glomerulonephritis overlapping with scabies.
PMID- 27512314
TI - Secret in the eyes - fish eye disease.
PMID- 27512315
TI - piRNAs and Their Functions in the Brain.
AB - Piwi-interacting RNAs (piRNAs) are the non-coding RNAs with 24-32 nucleotides
(nt). They exhibit stark differences in length, expression pattern, abundance,
and genomic organization when compared to micro-RNAs (miRNAs). There are hundreds
of thousands unique piRNA sequences in each species. Numerous piRNAs have been
identified and deposited in public databases. Since the piRNAs were originally
discovered and well-studied in the germline, a few other studies have reported
the presence of piRNAs in somatic cells including neurons. This paper reviewed
the common features, biogenesis, functions, and distributions of piRNAs and
summarized their specific functions in the brain. This review may provide new
insights and research direction for brain disorders.
PMID- 27512316
TI - From Yama to Samyama.
PMID- 27512317
TI - Yoga and heart rate variability: A comprehensive review of the literature.
AB - Heart rate variability (HRV) has been used as a proxy for health and fitness and
indicator of autonomic regulation and therefore, appears well placed to assess
the changes occurring with mind.-body practices that facilitate autonomic
balance. While many studies suggest that yoga influences HRV, such studies have
not been systematically reviewed. We aimed to systematically review all published
papers that report on yoga practices and HRV. A comprehensive search of multiple
databases was conducted and all studies that reported a measure of HRV associated
with any yoga practice were included. Studies were categorized by the study
design and type of yoga practice. A total of 59 studies were reviewed involving a
total of 2358 participants. Most studies were performed in India on relatively
small numbers of healthy male yoga practitioners during a single laboratory
session. Of the reviewed studies, 15 were randomized controlled trials with 6
having a Jadad score of 3. The reviewed studies suggest that yoga can affect
cardiac autonomic regulation with increased HRV and vagal dominance during yoga
practices. Regular yoga practitioners were also found to have increased vagal
tone at rest compared to non-yoga practitioners. It is premature to draw any firm
conclusions about yoga and HRV as most studies were of poor quality, with small
sample sizes and insufficient reporting of study design and statistical methods.
Rigorous studies with detailed reporting of yoga practices and any corresponding
changes in respiration are required to determine the effect of yoga on HRV.
PMID- 27512318
TI - Yoga-teaching protocol adapted for children with visual impairment.
AB - CONTEXT: Childhood visual deficiency impairs children's neuro-psychomotor
development, considerably affecting physical, mental, social, and emotional
health. Yoga's multifaceted approach may help children with visual impairment
(VI) to cope with their challenges. AIM: This study aimed to develop a special
protocol for teaching yoga to children with VI, and to evaluate their preferred
method of learning. METHODS: The study was carried out at Ramana Maharishi
Academy for the Blind, Bengaluru, South India. Forty-one students volunteered to
learn yoga practices, and classes were held weekly 5 days, 1 hr per session for
16 weeks. The study introduced a new method using a sequence of five teaching
steps: verbal instructions, tactile modeling, step-by-step teaching, learning in
a group, and physical guidance. A questionnaire concerning the preferred steps of
learning was then given to each student, and verbal answers were obtained.
RESULTS: A total of 33 (out of 41), aged 11.97 +/- 1.94, 15 girls and 18 boys
responded. Twenty-six (78.79%) chose physical guidance as their most favored
learning mode. CONCLUSIONS: Specially designed protocol may pave the way to
impart yoga in an exciting and comfortable way to children with VI. More studies
are needed to further investigate the effectiveness of this new yoga protocol in
similar settings.
PMID- 27512319
TI - Elements of yogic practice: Perceptions of students in healthcare programs.
AB - BACKGROUND: The practice of yoga has a long history as an integrated lifestyle
science. Those who have practiced yoga in its full form (including all eight
traditional aspects) find that it touches almost every aspect of their inter- and
intra-personal lives. Despite this rich history, the West has adopted limited
aspects of yoga practice. When understood narrowly as a physical fitness
practice, healthful benefits of yoga may be lost, possibly promoting body
consciousness and injury instead. AIM: To understand whether students in
healthcare programs view yoga from a physical fitness versus holistic
perspective, we explored perceptions of what constitute yoga's essential
practices. METHODS: We assessed endorsement of the eight limbs of yoga via the
acceptability of yoga survey. The sample (n = 498) was recruited from programs in
10 healthcare professions at a Northwestern university. Participants were
categorized as nonyogis, contemplators, yogis, and superyogis. RESULTS: Across
all groups, findings confirmed a narrow definition of yoga as portrayed in
popular media and gym-based yoga classes. Breathing and posture practices were
the most commonly endorsed practices, even among the sample's most seasoned yoga
practitioners. Ethical practices and daily commitments of introspection,
disciplined practice, or living with purity were least commonly associated with
yoga despite their foundational nature in yoga philosophy. Concentration and
meditation practices were only moderately endorsed as essential practices. Super
yogis endorsed a wider variety of limbs than nonyogis, contemplators, and yogis.
CONCLUSIONS: We offer a rationale for these findings along with recommendations
that may help augment the definition of yoga and hence maximize its benefits.
PMID- 27512320
TI - Impact of individualized yoga therapy on perceived quality of life performance on
cognitive tasks and depression among Type II diabetic patients.
AB - CONTEXT: An individualized approach of providing yoga support can address many of
the disease-related concerns indicated in the management of diabetes,
specifically the impact on other life activities and long-term functional
wellbeing. AIM: To analyze the role of regular yoga practice as a self-management
approach to achieve glycemic control and psychological wellbeing in Type II
diabetic patients. METHODS: Ninety-one subjects of both sexes responded to the
announcement and consented to participate in the study. This was a single group,
before and after yoga evaluation without control comparison. The fasting and
postprandial blood sugar, glycosylated hemoglobin (HBA1c), cognitive tasks,
depression, cognitive failure, and diabetic-related quality of life (QOL) were
measured as pretest. The subjects underwent one-to-one individualized yoga
therapy sessions, which included 12 supervised sessions spread over a 3-month
period. The posttest data were analyzed using paired t-test and Wilcoxon paired
rank test. RESULTS: Showed significant reduction in fasting blood sugar. QOL of
the diabetic patients had improved significantly. There was a significant
reduction in the frequency (mean difference of 7.58, P > 0.01) of depressive
symptoms and intensity of depression (mean difference 1.66, P > 0.05).
Concentration and attention span improved significantly and mean discrepancy
score reduced (mean difference 3.42, P > 0.01). There were no marked changes in
the postprandial blood sugar and HBA1c. CONCLUSION: Yoga practice enhances the
subjective wellbeing, QOL, improves mood and concentration, and facilitates
achievement of adequate glycemic control among Type II diabetic patients.
PMID- 27512321
TI - A randomized controlled study on assessment of health status, depression, and
anxiety in coal miners with chronic obstructive pulmonary disease following yoga
training.
AB - CONTEXT: Psychological comorbidities are prevalent in coal miners with chronic
obstructive pulmonary disease (COPD) and contribute to the severity of the
disease reducing their health status. Yoga has been shown to alleviate depression
and anxiety associated with other chronic diseases but in COPD not been fully
investigated. AIM: This study aimed to evaluate the role of yoga on health
status, depression, and anxiety in coal miners with COPD. MATERIALS AND METHODS:
This was a randomized trial with two study arms (yoga and control), which
enrolled 81 coal miners, ranging from 36 to 60 years with stage II and III stable
COPD. Both groups were either on conventional treatment or combination of
conventional care with yoga program for 12 weeks. RESULTS: Data were collected
through standardized questionnaires; COPD Assessment Test, Beck Depression
Inventory and State and Trait Anxiety Inventory at the beginning and the end of
the intervention. The yoga group showed statistically significant (P < 0.001)
improvements on all scales within the group, all significantly different (P <
0.001) from changes observed in the controls. No significant prepost changes were
observed in the control group (P > 0.05). CONCLUSION: Yoga program led to greater
improvement in physical and mental health status than did conventional care. Yoga
seems to be a safe, feasible, and effective treatment for patients with COPD.
There is a need to conduct more comprehensive, high-quality, evidence-based
studies to shed light on the current understanding of the efficacy of yoga in
these chronic conditions and identify unanswered questions.
PMID- 27512322
TI - Yoga protocol for treatment of breast cancer-related lymphedema.
AB - INTRODUCTION: Vaqas and Ryan (2003) advocated yoga and breathing exercises for
lymphedema. Narahari et al. (2007) developed an integrative medicine protocol for
lower-limb lymphedema using yoga. Studies have hypothesized that yoga plays a
similar role as that of central manual lymph drainage of Foldi's technique. This
study explains how we have used yoga and breathing as a self-care intervention
for breast cancer-related lymphedema (BCRL). METHODS: The study outcome was to
create a yoga protocol for BCRL. Selection of yoga was based on the actions of
muscles on joints, anatomical areas associated with different groups of lymph
nodes, stretching of skin, and method of breathing in each yoga. The protocol was
piloted in eight BCRL patients, observed its difficulties by interacting with
patients. A literature search was conducted in PubMed and Cochrane library to
identify the yoga protocols for BCRL. RESULTS: Twenty yoga and 5 breathing
exercises were adopted. They have slow, methodical joint movements which helped
patients to tolerate pain. Breathing was long and diaphragmatic. Flexion of
joints was coordinated with exhalation and extension with inhalation. Alternate
yoga was introduced to facilitate patients to perform complex movements. Yoga's
joint movements, initial positions, and mode of breathing were compared to two
other protocols. The volume reduced from 2.4 to 1.2 L in eight patients after
continuous practice of yoga and compression at home for 3 months. There was
improvement in the range of movement and intensity of pain. DISCUSSION: Yoga
exercises were selected on the basis of their role in chest expansion, maximizing
range of movements: flexion of large muscles, maximum stretch of skin, and thus
part-by-part lymph drainage from center and periphery. This protocol addressed
functional, volume, and movement issues of BCRL and was found to be superior to
other BCRL yoga protocols. However, this protocol needs to be tested in centers
routinely managing BCRL.
PMID- 27512323
TI - The effects of yoga practice in school physical education on children's motor
abilities and social behavior.
AB - BACKGROUND: In recent years, yoga programs in childhood have been implemented in
schools, to promote the development for children. AIM: To investigate the effects
of yoga program in physical education classes on the motor abilities and social
behavior parameters of 6-8-year-old children. METHODS: The study included 16
children from the 1(st) grade of a public elementary school in the South of
Brazil. The children participated in a 12-week intervention, twice weekly, with
45 min each session. To assess children's performance, we used the Bruininks
Oseretsky Test of Motor Proficiency - Second Edition, the flexibility test (sit
and reach - Eurofit, 1988), the Pictorial Scale of Perceived Competence and
Social Acceptance for Young Children and semi-structured interviews with
children, parents, and classroom' teacher. Data were analyzed with Wilcoxon test
and level of significance was 5%. RESULTS: The yoga program was well accepted by
children, children also demonstrated significant and positive changes in overall
motor abilities scores (balance, strength, and flexibility). In addition, the
interviews reported changing in social behavior and the use of the knowledge
learned in the program in contexts outside of school. CONCLUSION: These findings
suggest that the implementation of yoga practice in physical education lessons
contributed to children's development.
PMID- 27512324
TI - Kapalabhati pranayama: An answer to modern day polycystic ovarian syndrome and
coexisting metabolic syndrome?
AB - Breath, the vital force of life, is controlled positively by pranayama to ensure
homeostasis and wellbeing in humans. Kapalabhati is the rapid breathing technique
of pranayama, which is considered as a cure for various ailments. The possible
use of this technique to combat metabolic syndrome (MS) and polycystic ovarian
syndrome (PCOS) has been discussed in this article. Various published literature
from PubMed, Scopus, and theses were reviewed to reinforce the hypothesis that
this technique is the answer to ailments due to modernization. It was worthwhile
to note that Kapalabhati does combat various features of MS, but its efficacy
against PCOS is yet to be proven. However, since both syndromes arise due to a
common factor hyperinsulinemia primarily induced by stress in this modern world,
it is hypothesized that Kapalabhati holds good against PCOS too. Hence, in
conclusion, it can be said that it would be beneficial to conduct a study on PCOS
women to ascertain the efficacy of Kapalabhati in their population.
PMID- 27512325
TI - Mindfulness-based cognitive therapy in patients with late-life depression: A case
series.
AB - Depression is the most common mental illness in the elderly, and cost-effective
treatments are required. Therefore, this study is aimed at evaluating the
effectiveness of a mindfulness-based cognitive therapy (MBCT) on depressive
symptoms, mindfulness skills, acceptance, and quality of life across four domains
in patients with late-onset depression. A single case design with pre- and post
assessment was adopted. Five patients meeting the specified inclusion and
exclusion criteria were recruited for the study and assessed on the behavioral
analysis pro forma, geriatric depression scale, Hamilton depression rating scale,
Kentucky inventory of mindfulness skills, Acceptance and Action Questionnaire II,
The World Health Organization quality of life Assessment Brief version (WHOQO-L
BREF). The therapeutic program consisted of education regarding the nature of
depression, training in formal and informal mindfulness meditation, and cognitive
restructuring. A total of 8 sessions over 8 weeks were conducted for each
patient. The results of this study indicate clinically significant improvement in
the severity of depression, mindfulness skills, acceptance, and overall quality
of life in all 5 patients. Eight-week MBCT program has led to reduction in
depression and increased mindfulness skills, acceptance, and overall quality of
life in patients with late-life depression.
PMID- 27512326
TI - A rare case of branch retinal vein occlusion following Sirsasana.
AB - Sirsasana is a type of headstand postural yoga in which the body is completely
inverted. It is performed with or without wall support. In this position, the
body is held upright supported by the forearms, while the crown of the head rests
lightly on the floor. This is an advanced pose and should be attempted under the
supervision of a qualified yoga instructor. The practice of Sirsasana is
postulated to increase blood flow to the brain, improving memory, and other
intellectual functions. It is also known to cause causes raised intraocular
pressure, decompression retinopathy, glaucomatous visual field defects, central
retinal vein occlusion, progression of glaucoma, optic neuropathy, and
conjunctival varix thrombosis. We report a case of branch retinal vein occlusion
following Sirsasana in a patient with systemic hypertension.
PMID- 27512327
TI - Yoga as an adjunct modality for promotion of healthy use of information
technology.
PMID- 27512328
TI - What's new in emergencies, trauma, and shock: Intentional or accidental
hypothermia in Intensive Care Unit patients: Time to strike the colors?
PMID- 27512329
TI - In the blink of an eye: Instant countertransference and its application in modern
healthcare.
PMID- 27512330
TI - Hypothermia as a predictor for mortality in trauma patients at admittance to the
Intensive Care Unit.
AB - AIMS: To study the impact of hypothermia upon admission to the Intensive Care
Unit (ICU) on early and late mortality and to develop a prediction model for late
mortality in severely injured trauma patients. MATERIALS AND METHODS: A
multicenter retrospective cohort study was performed in adult trauma patients
admitted to the ICU of two Level-1 trauma centers between 2007 and 2012.
Hypothermia was defined as a core body temperature of <=35 degrees Celsius.
Logistic regression analyses were performed to quantify the effect of hypothermia
on 24-hour and 28-day mortality and to develop a prediction model. RESULTS: A
total of 953 patients were included, of which 354 patients had hypothermia (37%)
upon ICU admission. Patients were divided into a normothermic or hypothermic
group. Hypothermia was associated with a significantly increased mortality at 24
hours and 28 days (OR 2.72 (1.18-6.29 and OR 2.82 (1.83-4.35) resp.). The
variables included in the final prediction model were hypothermia, age, APACHE II
score (corrected for temperature), INR, platelet count, traumatic brain injury
and Injury Severity Score. The final prediction model discriminated between
survivors and non-survivors with high accuracy (AUC = 0.871, 95% CI 0.844-0.898).
CONCLUSIONS: Hypothermia, defined as a temperature <=35 degrees Celsius, is
common in critically ill trauma patients and is one of the most important
physiological predictors for early and late mortality in trauma patients. Trauma
patients admitted to the ICU may be at high risk for late mortality if the
patient is hypothermic, coagulopathic, severely injured and has traumatic brain
injury or an advanced age.
PMID- 27512331
TI - Extremes of shock index predicts death in trauma patients.
AB - CONTEXT: We noted a bimodal relationship between mortality and shock index (SI),
the ratio of heart rate to systolic blood pressure. AIMS: To determine if
extremes of SI can predict mortality in trauma patients. SETTINGS AND DESIGNS:
Retrospective evaluation of adult trauma patients at a tertiary care center from
2000 to 2012 in the United States. MATERIALS AND METHODS: We examined the SI in
trauma patients and determined the adjusted mortality for patients with and
without head injuries. STATISTICAL ANALYSIS USED: Descriptive statistics and
multivariable logistic regression. RESULTS: SI values demonstrated a U-shaped
relationship with mortality. Compared with patients with a SI between 0.5 and
0.7, patients with a SI of <0.3 had an odds ratio for death of 2.2 (95%
confidence interval [CI] 21.2-4.1) after adjustment for age, Glasgow Coma score,
and injury severity score while patients with SI >1.3 had an odds ratio of death
of 3.1. (95% CI 1.6-5.9). Elevated SI is associated with increased mortality in
patients with isolated torso injuries, and is associated with death at both low
and high values in patients with head injury. CONCLUSION: Our data indicate a
bimodal relationship between SI and mortality in head injured patients that
persists after correction for various co-factors. The distribution of mortality
is different between head injured patients and patients without head injuries.
Elevated SI predicts death in all trauma patients, but low SI values only predict
death in head injured patients.
PMID- 27512332
TI - Mortality in trauma patients with active arterial bleeding managed by
embolization or surgical packing: An observational cohort study of 66 patients.
AB - OBJECTIVE: Exsanguination due to coagulopathy and vascular injury is a common
cause of death among trauma patients. Arterial injury can be treated either by
angiography and embolization or by explorative laparotomy and surgical packing.
The purpose of this study was to compare 30-day mortality and blood product
consumption in trauma patients with active arterial haemorrhage in the abdominal
and/or pelvic region treated with either angiography and embolization or
explorative laparotomy and surgical packing. MATERIAL AND METHODS: From January
1(st) 2006 to December 31(st) 2011 2,173 patients with an ISS of >9 were admitted
to the Trauma Centre of Copenhagen University Hospital, Rigshospitalet, Denmark.
Of these, 66 patients met the inclusion criteria: age above 15 years and active
arterial haemorrhage from the abdominal and/or pelvic region verified by a CT
scan at admission. Gender, age, initial oxygen saturation, pulse rate and
respiratory rate, mechanism of injury, ISS, Probability of Survival, treatment
modality, 30-day mortality and number and type of blood products applied were
retrieved from the TARN database, patient records and the Danish Civil
Registration System. RESULTS: Thirty-one patients received angiography and
embolization, and 35 patients underwent exploratory laparotomy and surgical
packing. Gender, age, initial oxygen saturation, pulse rate and respiratory rate,
ISS and Probability of Survival were comparable in the two groups. CONCLUSION: A
significant increased risk of 30-day mortality (P = 0.04) was found in patients
with active bleeding treated with explorative laparotomy and surgical packing
compared to angiography and embolization when data was adjusted for age and ISS.
No statistical significant difference (P > 0.05) was found in number of
transfused blood products applied in the two groups of patients.
PMID- 27512333
TI - Assessment of cardiopulmonary resuscitation practices in emergency departments
for out-of-hospital cardiac arrest victims in Lebanon.
AB - BACKGROUND: The survival rate of out-of-hospital cardiac arrest (OHCA) victims in
Lebanon is low. A national policy on resuscitation practice is lacking. This
survey explored the practices of emergency physicians related to the
resuscitation of OHCA victims in Lebanon. METHODS: A sample of 705 physicians
working in emergency departments (EDs) was recruited and surveyed using the
LimeSurvey software (Carsten Schmitz, Germany). Seventy-five participants
responded, yielding 10.64% response rate. RESULTS: The most important factors in
the participants' decision to initiate or continue resuscitation were presence of
pulse on arrival (93.2%), underlying cardiac rhythm (93.1%), the physician's
ethical duty to resuscitate (93.2%), transport time to the ED (89%), and down
time (84.9%). The participants were optimistic regarding the survival of OHCA
victims (58.1% reporting > 10% survival) and reported frequent resuscitation
attempts in medically futile situations. The most frequently reported challenges
during resuscitation decisions were related to pressure or presence of victim's
family (38.8%) and lack of policy (30%). CONCLUSION: In our setting, physicians
often rely on well-established criteria for initiating/continuing resuscitation;
however, their decisions are also influenced by cultural factors such as victim's
family wishes. The findings support the need for a national policy on
resuscitation of OHCA victims.
PMID- 27512334
TI - Medical demographics in sub-Saharan Africa: Does the proportion of elderly
patients in accident and emergency units mirror life expectancy trends?
PMID- 27512335
TI - Delayed diagnosis of a thoracolumbar flexion-distraction injury.
PMID- 27512336
TI - The Need for Psychosocial Interventions to Facilitate the Transition to Extended
Release Naltrexone (XR-NTX) Treatment for Opioid Dependence: A Concise Review of
the Literature.
AB - Given the increase of opioid dependence and opioid-related morbidity and
mortality, improving treatment options for individuals with opioid dependence
warrants increased attention. This article provides a concise review of work in
this area. Remission from opioid dependence can be very difficult to sustain,
particularly in the absence of opioid replacement or opioid antagonist therapy.
For those who wish to transition from opioid use or opioid replacement therapy to
opioid antagonist therapy, a significant challenge can be the period of
withdrawal symptoms that must be endured prior to the initiation of opioid
antagonist therapy. Studies that have incorporated psychosocial interventions
into detoxification protocols have found that they can result in improved
treatment outcomes. Interventions based on Acceptance and Commitment Therapy have
shown promise in the treatment of clinical disorders that present with symptoms
similar to those of opioid withdrawal and have been found to positively impact
outcomes among those tapering from methadone. However, the use of an Acceptance
and Commitment Therapy-based intervention has yet to be studied among opioid
dependent patients transitioning to XR-NTX, and its value to those transitioning
to XR-NTX is currently unknown.
PMID- 27512337
TI - Interactions Between Internalizing Symptoms and Urgency in the Prediction of
Alcohol Use and Expectancies Among Low-Income, Minority Early Adolescents.
AB - This study examined whether urgency, a disposition to rash action under
conditions of strong emotion, moderates associations between internalizing
symptoms and alcohol use and related expectancies. Data from the Camden Youth
Development Study, a longitudinal, community-based study of early adolescents (N
= 144, mean age at intake = 11.9 years; 65% Hispanic, 30% African-American; 50%
male), were used. Self-report questionnaire measures of depressive symptoms,
social and generalized anxiety symptoms, urgency, alcohol use, and alcohol
expectancies were used. Mixed models were used to examine the effects of
internalizing symptoms, urgency, and their interaction on alcohol use and
expectancy trajectories over time. Depressive symptoms interacted with urgency
such that youth with high levels of both tended to have elevated levels of global
positive alcohol expectancies. Social anxiety symptoms interacted with urgency to
be associated with increasing levels of social behavior alcohol expectancies such
that youth with high levels of both tended to experience particular increases in
these expectancies over time. Generalized anxiety was not found to be associated
with alcohol-related constructs. Therefore, high levels of urgency combine with
depressive and social anxiety symptoms to be associated with particularly
increased risk for alcohol expectancies that are associated with later alcohol
use and problems, indicating particular risk for youth with these combinations of
personality traits and psychopathology symptoms.
PMID- 27512338
TI - Molecular Properties of Red Wine Compounds and Cardiometabolic Benefits.
AB - Wine has been used since the dawn of human civilization. Despite many health
benefits, there is still a lot of discussion about the real properties of its
components and its actions on cells and molecular interactions. A large part of
these issues permeate the fine line between the amount of alcohol that causes
problems to organic systems and the amount that could be beneficial for the
health. However, even after the process of fermentation, wine conserves different
organic compounds from grapes, such as polysaccharides, acids, and phenolic
compounds, such as flavonoids and nonflavonoids. These substances have known anti
inflammatory and antioxidant capacities, and are considered as regulatory agents
in cardiometabolic process. In this study, the main chemical components present
in the wine, its interaction with molecules and biological mechanisms, and their
interference with intra- and extracellular signaling are reviewed. Finally, the
properties of wine that may benefit cardiovascular system are also revised.
PMID- 27512340
TI - Resetting Human Naive Pluripotency.
AB - The rodent naive pluripotent state is believed to represent the preimplantation
inner cell mass state of the developing blastocyst and can derive self-renewing
pluripotent embryonic stem cells (ESCs) in vitro. Nevertheless, human ESCs
exhibit epigenetic, metabolic, and transcriptomic characteristics more akin to
primed pluripotent stem cells (PSCs) derived from the postimplantation epiblast.
Understanding the genetic and epigenetic mechanisms that constrain human ESCs in
the primed state is crucial for the human naive pluripotent state resetting and
numerous applications in regenerative medicine. In this review, we begin by
defining the naive and primed states in the murine model and compare the
epigenetic characteristics of those states to the human PSCs. We also examine the
various reprogramming schemes to derive the human naive pluripotent state.
Finally, we discuss future perspectives of studying and deriving the human naive
PSCs in the context of cellular engineering and regenerative medicine.
PMID- 27512339
TI - The Evolution of Epigenetics: From Prokaryotes to Humans and Its Biological
Consequences.
AB - The evolution process includes genetic alterations that started with prokaryotes
and now continues in humans. A distinct difference between prokaryotic
chromosomes and eukaryotic chromosomes involves histones. As evolution
progressed, genetic alterations accumulated and a mechanism for gene selection
developed. It was as if nature was experimenting to optimally utilize the gene
pool without changing individual gene sequences. This mechanism is called
epigenetics, as it is above the genome. Curiously, the mechanism of epigenetic
regulation in prokaryotes is strikingly different from that in eukaryotes, mainly
higher eukaryotes, like mammals. In fact, epigenetics plays a significant role in
the conserved process of embryogenesis and human development. Malfunction of
epigenetic regulation results in many types of undesirable effects, including
cardiovascular disease, metabolic disorders, autoimmune diseases, and cancer.
This review provides a comparative analysis and new insights into these aspects.
PMID- 27512341
TI - Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt
Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of
Presentation: A Rare Combination of Discordant Lymphomas.
AB - Discordant lymphoma is rare condition in which different types of malignant
lymphomas occurring in different anatomic sites. The two diseases may present
clinically as concurrent or sequential disease (10). Herein we are reporting a
Pakistani female in her 60s, a carrier of hepatitis B virus with multiple
comorbidities presented with cervical lymphadenopathy, diagnosed as Hodgkin's
lymphoma, mixed cellularity. During the staging workup, the patient was
discovered to have extensive bone marrow (BM) involvement by Burkitt
leukaemia/lymphoma (BL). Cytogenetic analysis revealed positivity for
t(8;14)(q24;q32) confirmed by Fluorescence In Situ Hybridization (FISH) for
IGH/MYC. Epstein-Barr virus (EBV) was demonstrated heavily in our case, with
(EBV) DNA of 24,295,560 copies/ml by PCR at time of presentation, in addition,
the neoplastic cells in both diagnostic tissues (cervical lymph node and BM)
demonstrated positivity for EBV. A diagnosis of concomitant EBV related
discordant lymphoma (classical Hodgkin lymphoma (cHL) and Burkitt lymphoma (BL)
in leukemic phase was made. Among all reported cases, this case is highly
exceptional because it is the first case of discordant/composite lymphoma, with
this combination and concomitant presentation. Since we are dealing with a case
with an exceptionally rare combination, we found it significant to elaborate more
on its clinical features, contributing factors including EBV role, response to
treatment, complications, and prognosis.
PMID- 27512342
TI - Cytokines and Prognostic Factors in Epithelial Ovarian Cancer.
AB - INTRODUCTION: Ovarian cancer has a high mortality and delayed diagnosis.
Inflammation is a risk factor for ovarian cancer, and the inflammatory response
is involved in almost all stages of tumor development. Immunohistochemical
staining in stroma and epithelium of a panel of cytokines in benign and malignant
ovarian neoplasm was evaluated. In addition, immunostaining was related to
prognostic factors in malignant tumors. METHOD: The study group comprised 28
ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of
cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5,
IL-6, and IL-10; and TNFR1). Chi-square test with Yates' correction was used,
which was considered significant if less than 0.05. RESULTS: TNFR1, IL-5, and IL
10 had more frequent immunostaining 2/3 in benign neoplasms compared with
malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2
in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in
the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of
the ovarian cancer stroma showed that histological grade 3 was significantly
correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free
survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more
frequently. CONCLUSION: IL-2 and TNFR1 stromal immunostaining are related
prognostic factors in ovarian cancer and can be the target of new therapeutic
strategies.
PMID- 27512343
TI - An evidence-based laparoscopic simulation curriculum shortens the clinical
learning curve and reduces surgical adverse events.
AB - BACKGROUND: Surgical simulation is becoming increasingly important in surgical
education. However, the method of simulation to be incorporated into a surgical
curriculum is unclear. We compared the effectiveness of a proficiency-based
preclinical simulation training in laparoscopy with conventional surgical
training and conventional surgical training interspersed with standard simulation
sessions. MATERIALS AND METHODS: In this prospective single-blinded trial, 30
final-year medical students were randomized into three groups, which differed in
the way they were exposed to laparoscopic simulation training. The control group
received only clinical training during residency, whereas the interval group
received clinical training in combination with simulation training. The Center
for Surgical Technologies Preclinical Training Program (CST PTP) group received a
proficiency-based preclinical simulation course during the final year of medical
school but was not exposed to any extra simulation training during surgical
residency. After 6 months of surgical residency, the influence on the learning
curve while performing five consecutive human laparoscopic cholecystectomies was
evaluated with motion tracking, time, Global Operative Assessment of Laparoscopic
Skills, and number of adverse events (perforation of gall bladder, bleeding, and
damage to liver tissue). RESULTS: The odds of adverse events were 4.5 (95%
confidence interval 1.3-15.3) and 3.9 (95% confidence interval 1.5-9.7) times
lower for the CST PTP group compared with the control and interval groups. For
raw time, corrected time, movements, path length, and Global Operative Assessment
of Laparoscopic Skills, the CST PTP trainees nearly always started at a better
level and were never outperformed by the other trainees. CONCLUSION: Proficiency
based preclinical training has a positive impact on the learning curve of a
laparoscopic cholecystectomy and diminishes adverse events.
PMID- 27512344
TI - A non-autonomous optimal control model of renewable energy production under the
aspect of fluctuating supply and learning by doing.
AB - Given the constantly raising world-wide energy demand and the accompanying
increase in greenhouse gas emissions that pushes the progression of climate
change, the possibly most important task in future is to find a carbon-low energy
supply that finds the right balance between sustainability and energy security.
For renewable energy generation, however, especially the second aspect turns out
to be difficult as the supply of renewable sources underlies strong volatility.
Further on, investment costs for new technologies are so high that
competitiveness with conventional energy forms is hard to achieve. To address
this issue, we analyze in this paper a non-autonomous optimal control model
considering the optimal composition of a portfolio that consists of fossil and
renewable energy and which is used to cover the energy demand of a small country.
While fossil energy is assumed to be constantly available, the supply of the
renewable resource fluctuates seasonally. We further on include learning effects
for the renewable energy technology, which will underline the importance of
considering the whole life span of such a technology for long-term energy
planning decisions.
PMID- 27512345
TI - Role of CaCO3 degrees Neutral Pair in Calcium Carbonate Crystallization.
AB - The molecular structure of the units that get incorporated into the nuclei of the
crystalline phase and sustain their growth is a fundamental issue in the pathway
from a supersaturated solution to the formation of crystals. Using a fluorescent
dye we have recorded the variation of the pH value in time along a gel where
CaCl2 and NaHCO3 counter-diffuse to crystallize CaCO3. The same pH-space-time
distribution maps were also computationally obtained using a chemical speciation
code (phreeqc). Using data arising from this model we investigated the space-time
evolution of the activity of the single species (ions and ion pairs) involved in
the crystallization process. Our combined results suggest that, whatever the
pathway from solution to crystals, the neutral pair CaCO3 degrees is a key
species in the CaCO3 precipitation system.
PMID- 27512346
TI - Internet-Based Interventions for Women's Sexual Dysfunction.
AB - The present paper gives an overview of the methodology and results of the first
decade of research into Internet-based interventions for women's sexual
dysfunction. The interventions, retrieved in a literature search, were mostly
well grounded on common theoretical models of sexual dysfunction and
psychological disorders, and most ingredients of the interventions were theory
informed. Most interventions offered Web-based therapeutic content within a more
or less preprogrammed structure. Most of these also offered prescheduled and/or
participant-initiated contact with a sexual health care professional. Comparative
effect studies showed improvements in sexual functioning as well as relational
functioning at the point of termination of the intervention period. Improvements
at posttreatment were generally maintained for several months after termination
of the active intervention period. The results of this review seem to warrant
further development of Internet-based interventions for women's sexual
dysfunctions.
PMID- 27512347
TI - Fibrocytes in the Pathogenesis of Chronic Fibrotic Lung Disease.
AB - Fibrocytes were initially described in 1999 and since that time there has been a
growing body of literature to suggest their importance in a number of chronic
lung diseases. It is now well established that fibrocytes derive from the bone
marrow and circulate within the peripheral blood. However, when injury occurs,
fibrocytes can travel to the site of damage via chemokine-mediated recruitment.
Recent studies suggest that fibrocyte numbers increase within the lung or
circulation during numerous disease processes. Although fibrocytes readily
differentiate into fibroblasts in vitro, whether they do so in vivo is still
unknown. The variety of pro-fibrotic mediators that are secreted by fibrocytes
makes it likely that they act via paracrine functions to influence the behavior
of resident lung cells. This review summarizes recent insights regarding
fibrocytes in asthma, scleroderma and IPF.
PMID- 27512348
TI - MiRNA in atopic dermatitis.
AB - MicroRNAs are relatively new molecules that have been widely studied in recent
years as to determine their exact function in the human body. It is suggested
that microRNAs control approx. 30% of all genes, making them one of the largest
groups that control the expression of proteins. Various functions of miRNAs have
already been described. In skin diseases, there are more and more studies
describing an altered expression of microRNAs in the skin or serum. Relatively
little is known about the function of these molecules in atopic dermatitis, which
prompted us to gather current reports on this subject.
PMID- 27512349
TI - In vivo studies of substances used in the cosmetic industry.
AB - Cosmetic producers are obliged to guarantee the safety and stability of their
products. The current legal regulations are based on the European Union Directive
(1223/2009) of 30 November 2009. The main aim of the directive is to formulate
criteria of safety of a cosmetic product and requirements that it must meet to be
placed on the market. A new cosmetic product is subjected to thorough
investigation prior to its introduction on the market. It should be studied not
only with respect to its safety, but also with respect to its effectiveness
declared by the producer. The studies are performed in vivo, by the contact or
epidermal patch tests on the human skin.
PMID- 27512350
TI - Medium dose ultraviolet A1 phototherapy and mRNA expression of interleukin 8,
interferon gamma, and chemokine receptor 4 in acute skin lesions in atopic
dermatitis.
AB - INTRODUCTION: Mechanisms responsible for UVA1 efficacy in atopic dermatitis (AD)
are not fully elucidated. AIM: To investigate IL-8, CCR-4, and IFN-gamma mRNA
expression in AD before and after UVA1, to identify correlations among them, and
to determine whether and to what degree mRNA expression is influenced by UVA1.
MATERIAL AND METHODS: Twenty-five patients with AD underwent medium dose UVA1
phototherapy at daily dosages of 10, 20, 30, 45, and then continuing 45 J/cm(2)
up to 20 days, from Monday to Friday for 4 weeks. Before and after UVA1, biopsies
from acute skin lesions were studied using reverse-transcription and RT-PCR.
RESULTS: The levels of CCR-4 mRNA correlated with those of IFN-gamma, both before
and after UVA1 phototherapy (p < 0.05). A significant correlation was found after
UVA1 between mRNA levels of IL-8 and IFN-gamma (p < 0.05). After UVA1 an increase
in IL-8 mRNA expression in comparison to the baseline assessment (p = 0.02) was
found, while no significant difference was revealed in the expression of CCR-4
and IFN-gamma mRNA. UVA1 improved both SCORAD and severity of AD (p < 0.001).
SCORAD and the severity of AD did not correlate with the degree of expression of
measured cytokine mRNA, neither before nor after UVA1. CONCLUSIONS: CCR-4 is
expressed in parallel with IFN-gamma in acute skin lesions of patients with AD
both before and after UVA1 phototherapy. UVA1 significantly improves SCORAD
index, lessens the severity of AD and increases the expression of IL-8, with no
direct effects on other studied molecules.
PMID- 27512351
TI - Prevalence of skin disorders in primary and secondary school age children in
Canakkale, Turkey: a community-based survey.
AB - INTRODUCTION: Skin lesions may be of dermatological importance, affect
appearance, and cause problems communicating with peers and may be especially
more significant in childhood. AIM: Information on the prevalence of pediatric
dermatoses in Western Turkey. This study was aimed to define the existing data.
MATERIAL AND METHODS: A cross-sectional study was conducted in Canakkale, Turkey,
in September-December 2013. It involved 1,957 students from five randomly
selected primary and secondary schools. Each student was interviewed for age,
gender, and family history, and a dermatologic examination was performed by a
dermatologist. Data were coded and analyzed. RESULTS: Of the students, 79.9%
revealed at least one dermatosis. The most common disease was benign neoplasms
(76%), followed by pigmentary disorders (26.8%), and xerosis (5.8%). In primary
schools, the acquired melanocytic nevus, hypopigmented macule, and xerosis; in
secondary school the acne was statistically significantly more common. Acne and
xerosis was more common in girls, and pityriasis alba was statistically more
common in boys. Students who had at least one dermatosis were positively
correlated with monthly income. CONCLUSIONS: In Turkish school age children, the
prevalence of dermatosis is 79.9%. It may be due to not using preventive means
for adequate protection from the sun and other environmental factors. Infectious
dermatosis and atopic dermatitis are rare and it may depend on the adequacy of
public health work.
PMID- 27512352
TI - Can mean platelet volume be used as a biomarker for asthma?
AB - INTRODUCTION: Platelets play important roles in airway inflammation and are
activated in inflammatory lung diseases, including asthma. AIM: We evaluated the
mean platelet volume (MPV), used as a marker of platelet activation, in asthmatic
patients during asymptomatic periods and exacerbations compared to healthy
controls to determine whether MPV can be used as an indicator of inflammation.
MATERIAL AND METHODS: Our patient group consisted of 95 children with
exacerbation of asthma who were admitted to our allergy clinic. The control group
consisted of 100 healthy children matched for age, gender, and ethnicity. Mean
platelet volume values of the patient group obtained during exacerbation of
asthma were compared to those of the same group during the asymptomatic period
and with the control group. We investigated factors that can affect the MPV
values of asthma patients, including infection, atopy, immunotherapy treatment,
and severity of asthma exacerbation. RESULTS: The patient group consisted of 50
(52.6%) boys and 45 (47.4%) girls with a mean age of 125 +/-38 months old. Mean
MPV values in the exacerbation period, the healthy period, and in the control
group were 8.1 +/-0.8 fl, 8.1 +/-1.06 fl, and 8.2 +/-0.9 fl, respectively; there
were no significant differences between groups (p > 0.05). The severity of
asthma, severity of asthma exacerbation, immunotherapy, coinfection, eosinophil
count, and IgE level also had no effect on MPV (p > 0.05). CONCLUSIONS: Although
platelets play a role in the pathophysiology of asthma, MPV measurement is
insufficient to detect inflammation through platelets.
PMID- 27512353
TI - Assessment of systemic inflammation with neutrophil-lymphocyte ratio in lichen
planus.
AB - INTRODUCTION: Lichen planus (LP) is a papulosquamous eruption of the skin and
mucous membranes. Although the exact pathogenesis of the disease remains unclear,
it is believed that LP represents an inflammatory disorder. Neutrophil-lymphocyte
(N/L) ratio is considered a systemic inflammatory marker that correlated with
severity of the diseases. AIM: To investigate whether N/L ratio increases in LP
and may be an independent severity marker for LP lesions. MATERIAL AND METHODS:
White blood cell (WBC), neutrophil and lymphocyte counts, N/L ratio, erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) were statistically compared
between the patient (n = 55) and the control group (n = 48). The relationship of
N/L ratio and the body surface area (BSA) was assessed. RESULTS: Erythrocyte
sedimentation rate and CRP were statistically higher in patients with LP than in
controls (p < 0.0001). Our analysis revealed a significantly higher level of N/L
ratio in patients with LP compared with controls, respectively (2.5 +/-1.1 (1.2
7.3) vs. 1.4 +/-0.4 (0.8-2.7), p < 0.0001). Body surface area (p = 0.001), CRP (p
= 0.006), and ESR (p = 0.003) were identified as possible predictors of N/L
ratio, but only BSA (p = 0.002) and ESR (p = 0.003) were found as significant
independent predictors in a multiple linear regression model. CONCLUSIONS: The
inflammatory process in LP was supported by our results. N/L ratio may have an
impact to show the inflammatory status in patients with LP as an inexpensive,
simple and effective predictor. It may be used for the severity and treatment
option of LP. But, N/L ratio and LP relationship could be confirmed by other
large prospective studies.
PMID- 27512354
TI - Thermographic assessment of skin prick tests in comparison with the routine
evaluation methods.
AB - INTRODUCTION: The skin prick test is still the first and basic procedure in the
diagnosis of allergic diseases. The possibility of using a sensitive
thermographic method supported by the mathematical model for the assessment of
skin test results will be highlighted in the studies. AIM: To compare the
proposed approach with routine planimetric and thermographic methods. MATERIAL
AND METHODS: A mathematical model of allergic reaction was developed. Simplifying
assumptions of the IgE-mediated skin reaction is the essence of the model.
Investigations were performed in a group of 40 patients. RESULTS: Using the
spatio-temporal evolution of temperature distributions, the ratios of the
histamine released from mast cells to the control histamine were determined. The
obtained values very well correlate with the standard evaluation of skin prick
tests (correlation coefficient = 0.98). CONCLUSIONS: The proposed method of skin
test evaluation presents several advantages. The continuous acquisition of data
provides the monitoring of time course of the allergic response. The transport of
mediator and its concentration were distinctly discriminated, which may be
diagnostically useful, especially for abnormal cases. The high sensitivity of the
method enables studying patients regardless of age and skin sensitivity.
PMID- 27512355
TI - Comparison of efficacy of chemical peeling with 25% trichloroacetic acid and 0.1%
retinoic acid for facial rejuvenation.
AB - INTRODUCTION: Skin aging is a problem which negatively affects the psyche of the
person, social relations, as well as work life and health and which compels the
patients to find appropriate treatment methods. Numerous treatment methods have
been developed in order to delay aging and to reduce the aging effects in
addition to having a younger, healthier and more beautiful facial appearance.
AIM: To compare the efficiency, cosmetic results and possible adverse effects of
the peeling treatment with 25% trichloroacetic acid (TCA) and 0.1% retinoic acid
for facial rejuvenation in patients presenting with skin aging. MATERIAL AND
METHODS: Fifty female patients in total presenting with medium and advanced
degree skin aging were subject to this study. Two separate treatment groups were
formed; the first group underwent chemical skin treatment with 25% TCA while the
other group was applied with 0.1% retinoic acid treatment. Following the 4
months' treatment the patients were controlled three times in total for post
lesional hypopigmentation, hyperpigmentation, scars, skin irritation and other
possible changes per month. The pretreatment and first follow-up visit, and final
control images were comparatively evaluated by three observers via specific
software. RESULTS: The healing rates of the group subject to retinoic acid were
statistically higher (p < 0.05) compared to patients in the TCA group in the
final follow-up visit following the treatment according to the first and second
observers. On the other hand, according to the third observer, patients applied
with retinoic acid presented with higher healing rates compared to those treated
with TCA, however; this rate was not statistically significant (p > 0.05). The
frequency of TCA- and retinoic acid-associated adverse effects was similar in
both groups (p > 0.05). As a result of both treatments, a reduction in the
quality of life scores as well as a pronounced recovery (p = 0.001) in the
quality of life of those patients with skin aging was observed. CONCLUSIONS: The
photo aging treatment option with 0.1% retinoic acid is cheaper and more feasible
for patients compared to 25% TCA, and it is also as reliable and effective as
TCA.
PMID- 27512356
TI - The correlation between anti phospholipase A2 specific IgE and clinical symptoms
after a bee sting in beekeepers.
AB - INTRODUCTION: Beekeepers are a group of people with high exposure to honeybee
stings and with a very high risk of allergy to bee venom. Therefore, they are a
proper population to study the correlations between clinical symptoms and results
of diagnostic tests. AIM: The primary aim of our study was to assess the
correlations between total IgE, venom- and phospholipase A2-specific IgE and
clinical symptoms after a bee sting in beekeepers. The secondary aim was to
compare the results of diagnostic tests in beekeepers and in individuals with
standard exposure to bees. MATERIAL AND METHODS: Fifty-four individuals were
divided into two groups: beekeepers and control group. The levels of total IgE
(tIgE), venom-specific IgE (venom sIgE), and phospholipase A2-specific IgE
(phospholipase A2 sIgE) were analyzed. RESULTS: Our study showed no statistically
significant correlation between the clinical symptoms after a sting and tIgE in
the entire analyzed group. There was also no correlation between venom sIgE level
and clinical symptoms either in beekeepers or in the group with standard exposure
to bees. We observed a statistically significant correlation between
phospholipase A2 sIgE level and clinical signs after a sting in the group of
beekeepers, whereas no such correlation was detected in the control group.
Significantly higher venom-specific IgE levels in the beekeepers, as compared to
control individuals were shown. CONCLUSIONS: In beekeepers, the severity of
clinical symptoms after a bee sting correlated better with phospholipase A2 sIgE
than with venom sIgE levels.
PMID- 27512357
TI - Selected immunological parameters in clinical evaluation of patients with atopic
dermatitis.
AB - INTRODUCTION: It has been suggested that soluble immune receptors (SIRs) such as
sCD25 and sCD30 may serve as potential biomarkers in evaluation of atopic
dermatitis (AD). Previous studies clearly indicated that serum levels of
interleukin (IL)-13 and total IgE (tIgE) might be potentially useful in the
evaluation of patents with AD. AIM: To evaluate whether serum levels of sCD25 and
sCD30 are suitable biomarkers of AD. Moreover, we have decided to estimate the
usefulness of tIgE and IL-13 serum level determination in the evaluated
population. MATERIAL AND METHODS: A group of 102 AD patients was investigated.
Serum concentrations of sCD30, sCD25, IL-13 and tIgE were measured. The clinical
phenotype of AD was classified as extrinsic (ADe) or intrinsic (ADi) based on the
presence of IgE. Statistical analysis was performed to estimate correlations
between obtained results and clinical features of the population such as AD
phenotype, age, disease extent and severity. RESULTS: Extrinsic AD was diagnosed
in 71% of patients, while ADi phenotype was observed in 29% of the investigated
population. A negative correlation between serum levels of sCD25 and sCD30 and
disease severity as well patients' age was established. Serum levels of IL-13 did
not reach the cut-off point set by the manufacturer. A positive correlation
between serum levels of total IgE and disease severity and patients' age was
observed. CONCLUSIONS: This paper shows that serum levels of sCD25 and sCD30 as
well as tIgE are age dependent. Determination of serum levels of sCD25, sCD30 and
IL-13 is not useful in everyday practice.
PMID- 27512358
TI - The relationship between body mass index, waist circumference and psoriatic
arthritis in the Turkish population.
AB - INTRODUCTION: Psoriasis is a chronic, immune-mediated inflammatory disease
predominantly affecting the skin, with a complex aetiology. Recently it has been
suggested that the chronic inflammation of psoriasis may cause metabolic and
vascular disorders. The relationship between obesity and psoriatic arthritis
(PsA) is not clear, and there are insufficient prospective studies addressing
this subject. AIM: To investigate the relationship between psoriatic arthritis,
severity of psoriasis and obesity in the Turkish population. MATERIAL AND
METHODS: Patient data from psoriasis outpatient clinics from February 2007 to
July 2013 were reviewed retrospectively using the Psoriasis-Turkey (PSR-TR)
registration system. Patients' age, onset age, body mass index (BMI), waist
circumference, psoriasis area and severity index (PASI), and arthritis
information were reviewed. In the outpatient clinics, patients who had joint pain
consulted rheumatology clinics. The CASPAR criteria were used for the diagnosis
of arthritis. RESULTS: A total of 443 males and 495 females enrolled in this
study. The mean age of females was 43.9 years (18-93 years) and the mean age of
males was 44.6 years (18-89 years). A total of 231 (25%) patients had psoriatic
arthritis. Investigation of the relationship between PASI, BMI, waist
circumference (WC) and arthritis revealed a statistically significant
relationship between each variable. CONCLUSIONS: In this study we observed a
relationship between PsA and high BMI, high WC and high PASI. Psoriatic arthritis
is a chronic inflammatory disorder and a chronic inflammatory state induced by
adiposity may lead to PsA.
PMID- 27512359
TI - The effect of an emollient with benfothiamine and Biolin prebiotic on the
improvement of epidermal skin function.
AB - INTRODUCTION: Complications of diabetes can damage internal organs and the skin.
Diabetic skin, irritated and dry, is susceptible to skin infections. However
little is known about influence of emollients on biophysical changes in skin
during diabetes. AIM: To evaluate clinical skin changes after application of
emollients with benfothiamine and Biolin prebiotic and to assess changes in
biophysical parameters of the skin before and 4 weeks after daily application of
an emollient. MATERIAL AND METHODS: We recruited 50 patients with diabetes
mellitus type 1 (DM1) or type 2 (DM2). All participants applied emollients on
their left forearms and left shins for 4 weeks. The biophysical properties: pH,
transepidermal water loss (TEWL), hydration of the stratum corneum and sebum
content were measured and compared to those before enrollment to the study, after
1 h, 1 week and 4 weeks after application of an emollient. RESULTS: After 4 weeks
of treatment, there was an increase in skin hydration (40.61 +/-19.03 vs. 48.83
+/-15.51), pH (5.11 +/-0.56 to 5.27 +/-0.48) and sebum content (22.16 +/-8.67 to
63.99 +/-25.41) and a decrease in TEWL (12.54 +/-5.6 vs. 9.85 +/-5.69 g/m(2)/h)
on forearms (p < 0.05 for all comparisons). On lower legs, significant changes in
skin hydration (37.21 +/-14.01 vs. 43.95 +/-12.67), pH (5.04 +/-0.57 to 5.31 +/
0.49), sebum content (25.82 +/-10.46 to 72.63 +/-31.23) and TEWL (8.87 +/-4.05
vs. 7.39 +/-3.22 g/m(2)/h) were observed (p < 0.05 for all comparisons).
CONCLUSIONS: Our study provides an insight into changes in diabetic skin after
application of an emollient. To our knowledge, this is the first report on the
emollient containing benfothiamine and Biolin prebiotic and its influence on
biophysical parameters of epidermis.
PMID- 27512360
TI - Thyroid abnormalities in paediatric patients with vitiligo: retrospective study.
AB - INTRODUCTION: The association between vitiligo and thyroid disease is not fully
investigated especially in paediatric patients. AIM: To determine the incidence
of vitiligo and thyroid disorders in children. This is the first report from
middle Anatolia and the second report from Turkey. MATERIAL AND METHODS: A
retrospective chart review was performed to examine the presence of thyroid
abnormalities in paediatric patients who had been admitted to the dermatology
department with vitiligo. RESULTS: A total of 155 paediatric patients, including
80 (52%) male and 75 (48%) female patients were included. The mean age was 8.6
years. Non segmental vitiligo was the most common type of the disease in 140
(90%) reviewed patients, while segmental vitiligo appeared only in 15 (10%)
patients. The mean onset of vitiligo was 5.6 +/-0.9 years. A family history of
vitiligo was found in 14 (9%) children. Thirty-four (22%) patients had thyroid
function tests and/or thyroid autoantibody abnormality. All of these patients had
non segmental vitiligo. It was statistically significant (p < 0.05) in types of
vitiligo and thyroid disease parameters. CONCLUSIONS: Our results show that it
may be useful to screen thyroid in children with non segmental vitiligo.
PMID- 27512361
TI - Extensive, neglected basal cell carcinoma of the half of the face-surgical
treatment and reconstruction with an anterolateral microvascular thigh flap.
PMID- 27512362
TI - Photosensitive pityriasis rubra pilaris.
PMID- 27512363
TI - Could aluminum be a new hidden allergen in type 1 hypersensitivity reactions when
used as a drug additive?
PMID- 27512364
TI - Target Speaker Detection with Concealed EEG Around the Ear.
AB - Target speaker identification is essential for speech enhancement algorithms in
assistive devices aimed toward helping the hearing impaired. Several recent
studies have reported that target speaker identification is possible through
electroencephalography (EEG) recordings. If the EEG system could be reduced to
acceptable size while retaining the signal quality, hearing aids could benefit
from the integration with concealed EEG. To compare the performance of a
multichannel around-the-ear EEG system with high-density cap EEG recordings an
envelope tracking algorithm was applied in a competitive speaker paradigm. The
data from 20 normal hearing listeners were concurrently collected from the
traditional state-of-the-art laboratory wired EEG system and a wireless mobile
EEG system with two bilaterally-placed around-the-ear electrode arrays
(cEEGrids). The results show that the cEEGrid ear-EEG technology captured neural
signals that allowed the identification of the attended speaker above chance
level, with 69.3% accuracy, while cap-EEG signals resulted in the accuracy of
84.8%. Further analyses investigated the influence of ear-EEG signal quality and
revealed that the envelope tracking procedure was unaffected by variability in
channel impedances. We conclude that the quality of concealed ear-EEG recordings
as acquired with the cEEGrid array has potential to be used in the brain-computer
interface steering of hearing aids.
PMID- 27512365
TI - Synthesis and Biological Evaluation of Thiophene-Based Cannabinoid Receptor Type
2 Radiotracers for PET Imaging.
AB - Over the past two decades, our understanding of the endocannabinoid system has
greatly improved due to the wealth of results obtained from exploratory studies.
Currently, two cannabinoid receptor subtypes have been well-characterized. The
cannabinoid receptor type 1 (CB1) is widely expressed in the central nervous
system, while the levels of the cannabinoid receptor type 2 (CB2) in the brain
and spinal cord of healthy individuals are relatively low. However, recent
studies demonstrated a CB2 upregulation on activated microglia upon
neuroinflammation, an indicator of neurodegeneration. Our research group aims to
develop a suitable positron emission tomography (PET) tracer to visualize the CB2
receptor in patients suffering from neurodegenerative diseases. Herein we report
two novel thiophene-based (11)C-labeled PET ligands designated [(11)C]AAT-015 and
[(11)C]AAT-778. The reference compounds were synthesized using Gewald reaction
conditions to obtain the aminothiophene intermediates, followed by amide
formation. Saponification of the esters provided their corresponding precursors.
Binding affinity studies revealed Ki-values of 3.3 +/- 0.5 nM (CB2) and 1.0 +/-
0.2 MUM (CB1) for AAT-015. AAT-778 showed similar Ki-values of 4.3 +/- 0.7 nM
(CB2) and 1.1 +/- 0.1 MUM (CB1). Radiosynthesis was carried out under basic
conditions using [(11)C]iodomethane as methylating agent. After semi-preparative
HPLC purification both radiolabeled compounds were obtained in 99% radiochemical
purity and the radiochemical yields ranged from 12 to 37%. Specific activity was
between 96 and 449 GBq/MUmol for both tracers. In order to demonstrate CB2
specificity of [(11)C]AAT-015 and [(11)C]AAT-778, we carried out autoradiography
studies using CB2-positive mouse/rat spleen tissues. The obtained results
revealed unspecific binding in spleen tissue that was not blocked by an excess of
CB2-specific ligand GW402833. For in vivo analysis, [(11)C]AAT-015 was
administered to healthy rats via tail-vein injection. Evaluation of the CB2
positive spleen, however, showed no accumulation of the radiotracer. Despite the
promising in vitro binding affinities, specific binding of [(11)C]AAT-015, and
[(11)C]AAT-778 could not be demonstrated.
PMID- 27512366
TI - Corrigendum: Perceptual factors contribute more than acoustical factors to sound
localization abilities with virtual sources.
AB - [This corrects the article on p. 451 in vol. 8, PMID: 25688182.].
PMID- 27512367
TI - Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery.
AB - Brain plasticity after stroke remains poorly understood. Patients may improve
spontaneously within the first 3 months and then more slowly in the coming year.
The first day, decreased edema and reperfusion of the ischemic penumbra may
possibly account for these phenomena, but the improvement during the next weeks
suggests plasticity phenomena and cortical reorganization of the brain ischemic
areas and of more remote areas. Indeed, the injured ischemic motor cortex has a
reduced cortical excitability at the acute phase and a suspension of the
topographic representation of affected muscles, whereas the contralateral motor
cortex has an increased excitability and an enlarged somatomotor representation;
furthermore, contralateral cortex exerts a transcallosal interhemispheric
inhibition on the ischemic cortex. This results from the imbalance of the
physiological reciprocal interhemispheric inhibition of each hemisphere on the
other, contributing to worsening of neurological deficit. Cortical excitability
is measurable through transcranial magnetic stimulation (TMS) and prognosis has
been established according to the presence of motor evoked potentials (MEP) at
the acute phase of stroke, which is predictive of better recovery. Conversely,
the lack of response to early stimulation is associated with a poor functional
outcome. Non-invasive stimulation techniques such as repetitive TMS (rTMS) or
transcranial direct current stimulation (tDCS) have the potential to modulate
brain cortical excitability with long lasting effects. In the setting of
cerebrovascular disease, around 1000 stroke subjects have been included in
placebo-controlled trials so far, most often with an objective of promoting motor
recovery of the upper limb. High frequency repetitive stimulation (>3 Hz) rTMS,
aiming to increase excitability of the ischemic cortex, or low frequency
repetitive stimulation (<=1 Hz), aiming to reduce excitability of the
contralateral homonymous cortex, or combined therapies, have shown various
effects on the functional disability score and neurological scales of treated
patients and on the duration of the treatment. We review here the patients'
characteristics and parameters of stimulation that could predict a good response,
as well as safety issues. At last, we review what we have learnt from
experimental studies and discuss potential directions to conduct future studies.
PMID- 27512368
TI - Non-invasive Brain Stimulation, a Tool to Revert Maladaptive Plasticity in
Neuropathic Pain.
AB - Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been
extensively studied in chronic pain. A hypothetic mechanism of action would be to
prevent or revert the ongoing maladaptive plasticity within the pain matrix. In
this review, the authors discuss the mechanisms underlying the development of
maladaptive plasticity in patients with chronic pain and the putative mechanisms
of NIBS in modulating synaptic plasticity in neuropathic pain conditions.
PMID- 27512369
TI - Interoception and Positive Symptoms in Schizophrenia.
AB - The present study focuses on the multifaceted concept of self-disturbance in
schizophrenia, adding knowledge about a not yet investigated aspect, which is the
interoceptive accuracy. Starting from the assumption that interoceptive accuracy
requires an intact sense of self, which otherwise was proved to be altered in
schizophrenia, the aim of the present study was to explore interoceptive accuracy
in a group of schizophrenia patients, compared to healthy controls. Furthermore,
the possible association between interoceptive accuracy and patients' positive
and negative symptomatology was assessed. To pursue these goals, a group of 23
schizophrenia patients and a group of 23 healthy controls performed a heartbeat
perception task. Patients' symptomatology was assessed by means of the Positive
and Negative Syndrome Scale (PANSS). Results demonstrated significantly lower
interoceptive accuracy in schizophrenia patients compared to healthy controls.
This difference was not accounted for participants' age, BMI, anxiety levels, and
heart rate. Furthermore, patients' illness severity, attention and
pharmacological treatment did not influence their interoceptive accuracy levels.
Interestingly, a strong positive relation between interoceptive accuracy and
positive symptoms severity, especially Grandiosity, was found. The present
results demonstrate for the first time that interoceptive accuracy is altered in
schizophrenia. Furthermore, they prove a specific association between
interoceptive accuracy and positive symptomatology, suggesting that the symptom
Grandiosity might be protective against an altered basic sense of self in
patients characterized by higher sensibility to their inner bodily sensations.
PMID- 27512370
TI - Anterior Cingulate Cortico-Hippocampal Dysconnectivity in Unaffected Relatives of
Schizophrenia Patients: A Stochastic Dynamic Causal Modeling Study.
AB - Familial risk plays a significant role in the etiology of schizophrenia (SZ).
Many studies using neuroimaging have demonstrated structural and functional
alterations in relatives of SZ patients, with significant results found in
diverse brain regions involving the anterior cingulate cortex (ACC), caudate,
dorsolateral prefrontal cortex (DLPFC), and hippocampus. This study investigated
whether unaffected relatives of first episode SZ differ from healthy controls
(HCs) in effective connectivity measures among these regions. Forty-six
unaffected first-degree relatives of first episode SZ patients-according to the
DSM-IV-were studied. Fifty HCs were included for comparison. All subjects
underwent resting state functional magnetic resonance imaging (fMRI). We used
stochastic dynamic causal modeling (sDCM) to estimate the directed connections
between the left ACC, right ACC, left caudate, right caudate, left DLPFC, left
hippocampus, and right hippocampus. We used Bayesian parameter averaging (BPA) to
characterize the differences. The BPA results showed hyperconnectivity from the
left ACC to right hippocampus and hypoconnectivity from the right ACC to right
hippocampus in SZ relatives compared to HCs. The pattern of anterior cingulate
cortico-hippocampal connectivity in SZ relatives may be a familial feature of SZ
risk, appearing to reflect familial susceptibility for SZ.
PMID- 27512371
TI - Cortical Gamma Oscillations: Details of Their Genesis Preclude a Role in
Cognition.
PMID- 27512372
TI - volBrain: An Online MRI Brain Volumetry System.
AB - The amount of medical image data produced in clinical and research settings is
rapidly growing resulting in vast amount of data to analyze. Automatic and
reliable quantitative analysis tools, including segmentation, allow to analyze
brain development and to understand specific patterns of many neurological
diseases. This field has recently experienced many advances with successful
techniques based on non-linear warping and label fusion. In this work we present
a novel and fully automatic pipeline for volumetric brain analysis based on multi
atlas label fusion technology that is able to provide accurate volumetric
information at different levels of detail in a short time. This method is
available through the volBrain online web interface (http://volbrain.upv.es),
which is publically and freely accessible to the scientific community. Our new
framework has been compared with current state-of-the-art methods showing very
competitive results.
PMID- 27512373
TI - Gabor frame sets of invariance: a Hamiltonian approach to Gabor frame
deformations.
AB - In this work we study families of pairs of window functions and lattices which
lead to Gabor frames which all possess the same frame bounds. To be more precise,
for every generalized Gaussian g, we will construct an uncountable family of
lattices [Formula: see text] such that each pairing of g with some [Formula: see
text] yields a Gabor frame, and all pairings yield the same frame bounds. On the
other hand, for each lattice we will find a countable family of generalized
Gaussians [Formula: see text] such that each pairing leaves the frame bounds
invariant. Therefore, we are tempted to speak about Gabor Frame Sets of
Invariance.
PMID- 27512374
TI - Sub-toxic Ethanol Exposure Modulates Gene Expression and Enzyme Activity of
Antioxidant Systems to Provide Neuroprotection in Hippocampal HT22 Cells.
AB - Ethanol is known to cause severe systemic damage often explained as secondary to
oxidative stress. Brain is particularly vulnerable to ethanol-induced reactive
oxygen species (ROS) because the high amounts of lipids, and because nerve cell
membranes contain high amounts of peroxidable fatty acids. Usually these effects
of ethanol are associated to high and/or chronic exposure to ethanol. However, as
we show in this manuscript, a low and acute dose of ethanol trigger a completely
different response in hippocampal cells. Thus, we have observed that 0.1% ethanol
exposure to HT22 cells, a murine hippocampal-derived cell line, increases the
transcriptional expression of different genes belonging to the classical,
glutathione/glutaredoxin and thioredoxin/peroxiredoxin antioxidant systems, these
including Sod1, Sod2, Gpx1, Gclc, and Txnrd1. Paralleling these changes, enzyme
activities of total superoxide dismutase (tSOD), catalase, total glutathione
peroxidase (tGPx), glutathione-S-reductase (GSR), and total thioredoxin reductase
(tTXNRD), were all increased, while the generation of thiobarbituric acid
reactive substances (TBARS), as indicators of lipid peroxidation, and glutathione
levels remained unaltered. Ethanol exposure did not affect cell viability or cell
growing as assessed by real-time cell culture monitoring, indicating that low
ethanol doses are not deleterious for hippocampal cells, but rather prevented
glutamate-induced excitotoxicity. In summary, we conclude that sub-toxic exposure
to ethanol may well be neuroprotective against oxidative insults in hippocampal
cells.
PMID- 27512375
TI - Doxorubicin Induces Inflammatory Modulation and Metabolic Dysregulation in
Diabetic Skeletal Muscle.
AB - Anti-cancer agent doxorubicin (DOX) has been demonstrated to worsen insulin
signaling, engender muscle atrophy, trigger pro-inflammation, and induce a shift
to anaerobic glycolytic metabolism in skeletal muscle. The myotoxicity of DOX in
diabetic skeletal muscle remains largely unclear. This study examined the effects
of DOX on insulin signaling, muscle atrophy, pro-/anti-inflammatory
microenvironment, and glycolysis metabolic regulation in skeletal muscle of db/db
diabetic and db/+ non-diabetic mice. Non-diabetic db/+ mice and diabetic db/db
mice were randomly assigned to the following groups: db/+CON, db/+DOX, db/dbCON,
and db/dbDOX. Mice in db/+DOX and db/dbDOX groups were intraperitoneally injected
with DOX at a dose of 15 mg per kg body weight whereas mice in db/+CON and
db/dbCON groups were injected with the same volume of saline instead of DOX.
Gastrocnemius was immediately harvested, weighed, washed with cold phosphate
buffered saline, frozen in liquid nitrogen, and stored at -80 degrees C for later
analysis. The effects of DOX on diabetic muscle were neither seen in insulin
signaling markers (Glut4, pIRS1Ser(636/639), and pAktSer(473)) nor muscle atrophy
markers (muscle mass, MuRF1 and MAFbx). However, DOX exposure resulted in
enhancement of pro-inflammatory favoring microenvironment (as indicated by TNF
alpha, HIFalpha and pNFkappaBp65) accompanied by diminution of anti-inflammatory
favoring microenvironment (as indicated by IL15, PGC1alpha and pAMPKbeta1Ser108).
Metabolism of diabetic muscle was shifted to anaerobic glycolysis after DOX
exposure as demonstrated by our analyses of PDK4, LDH and pACCSer(79). Our
results demonstrated that there might be a link between inflammatory modulation
and the dysregulation of aerobic glycolytic metabolism in DOX-injured diabetic
skeletal muscle. These findings help to understand the pathogenesis of DOX
induced myotoxicity in diabetic muscle.
PMID- 27512376
TI - New Imaging Methods for Non-invasive Assessment of Mechanical, Structural, and
Biochemical Properties of Human Achilles Tendon: A Mini Review.
AB - The mechanical properties of tendon play a fundamental role to passively transmit
forces from muscle to bone, withstand sudden stretches, and act as a mechanical
buffer allowing the muscle to work more efficiently. The use of non-invasive
imaging methods for the assessment of human tendon's mechanical, structural, and
biochemical properties in vivo is relatively young in sports medicine, clinical
practice, and basic science. Non-invasive assessment of the tendon properties may
enhance the diagnosis of tendon injury and the characterization of recovery
treatments. While ultrasonographic imaging is the most popular tool to assess the
tendon's structural and indirectly, mechanical properties, ultrasonographic
elastography, and ultra-high field magnetic resonance imaging (UHF MRI) have
recently emerged as potentially powerful techniques to explore tendon tissues.
This paper highlights some methodological cautions associated with conventional
ultrasonography and perspectives for in vivo human Achilles tendon assessment
using ultrasonographic elastography and UHF MRI.
PMID- 27512377
TI - System, Subsystem, Hive: Boundary Problems in Computational Theories of
Consciousness.
AB - A computational theory of consciousness should include a quantitative measure of
consciousness, or MoC, that (i) would reveal to what extent a given system is
conscious, (ii) would make it possible to compare not only different systems, but
also the same system at different times, and (iii) would be graded, because so is
consciousness. However, unless its design is properly constrained, such an MoC
gives rise to what we call the boundary problem: an MoC that labels a system as
conscious will do so for some-perhaps most-of its subsystems, as well as for
irrelevantly extended systems (e.g., the original system augmented with physical
appendages that contribute nothing to the properties supposedly supporting
consciousness), and for aggregates of individually conscious systems (e.g.,
groups of people). This problem suggests that the properties that are being
measured are epiphenomenal to consciousness, or else it implies a bizarre
proliferation of minds. We propose that a solution to the boundary problem can be
found by identifying properties that are intrinsic or systemic: properties that
clearly differentiate between systems whose existence is a matter of fact, as
opposed to those whose existence is a matter of interpretation (in the eye of the
beholder). We argue that if a putative MoC can be shown to be systemic, this ipso
facto resolves any associated boundary issues. As test cases, we analyze two
recent theories of consciousness in light of our definitions: the Integrated
Information Theory and the Geometric Theory of consciousness.
PMID- 27512378
TI - Holistic Patterns as an Instrument for Predicting the Performance of Promising
Young Soccer Players - A 3-Years Longitudinal Study.
AB - Multidimensional and dynamic talent models represent the current state of the
art, but these demands have hardly ever been implemented so far. One reason for
this could be the methodological problems associated with these requirements.
This paper will present a proposal for dealing with this, namely for examining
the development of young soccer players holistically. The patterns formed by the
constructs net hope, motor abilities, technical skills and biological maturity
were examined, as well as the way in which these holistic patterns are related to
subsequent sporting success. 119 young elite soccer players were questioned and
tested three times at intervals of 1 year, beginning at the age of 12. At the age
of 15, the level of performance reached by the players was determined. At all
three measuring points, four patterns were identified, which displayed partial
structural and high individual stability. The highly skilled players, scoring
above average on all factors - but not necessarily those having the highest
overall scores - were significantly more likely to advance to the highest level
of performance. Failure-fearing fit players, i.e., physically strong, early
developed players but with some technical weaknesses, have good chances of
reaching the middle performance level. In contrast, none of the achievement
oriented, highly skilled, late-matured or late-matured, low skilled players
reached the highest performance level. The results indicate the importance of
holistic approaches for predicting performance among promising soccer talents in
the medium-term and thus provide valuable clues for their selection and
promotion.
PMID- 27512379
TI - The Role of Metarepresentation in the Production and Resolution of Referring
Expressions.
AB - In this paper we consider the potential role of metarepresentation-the
representation of another representation, or as commonly considered within
cognitive science, the mental representation of another individual's knowledge
and beliefs-in mediating definite reference and common ground in conversation.
Using dialogues from a referential communication study in which speakers
conversed in succession with two different addressees, we highlight ways in which
interlocutors work together to successfully refer to objects, and achieve shared
conceptualizations. We briefly review accounts of how such shared
conceptualizations could be represented in memory, from simple associations
between label and referent, to "triple co-presence" representations that track
interlocutors in an episode of referring, to more elaborate metarepresentations
that invoke theory of mind, mutual knowledge, or a model of a conversational
partner. We consider how some forms of metarepresentation, once created and
activated, could account for definite reference in conversation by appealing to
ordinary processes in memory. We conclude that any representations that capture
information about others' perspectives are likely to be relatively simple and
subject to the same kinds of constraints on attention and memory that influence
other kinds of cognitive representations.
PMID- 27512380
TI - Editorial: From Meaning of Working to Meaningful Lives: The Challenges of
Expanding Decent Work.
PMID- 27512381
TI - Orthographic Activation in L2 Spoken Word Recognition Depends on Proficiency:
Evidence from Eye-Tracking.
AB - The use of orthographic and phonological information in spoken word recognition
was studied in a visual world task where L1 Finnish learners of L2 French (n =
64) and L1 French native speakers (n = 24) were asked to match spoken word forms
with printed words while their eye movements were recorded. In Experiment 1,
French target words were contrasted with competitors having a longer ( vs.
) or a shorter word initial phonological overlap ( vs. ) and
an identical orthographic overlap. In Experiment 2, target words were contrasted
with competitors of either longer ( vs. ) or shorter word initial
orthographic overlap ( vs. ) and of an identical phonological
overlap. A general phonological effect was observed in the L2 listener group but
not in the L1 control group. No general orthographic effects were observed in the
L2 or L1 groups, but a significant effect of proficiency was observed for
orthographic overlap over time: higher proficiency L2 listeners used also
orthographic information in the matching task in a time-window from 400 to 700
ms, whereas no such effect was observed for lower proficiency listeners. These
results suggest that the activation of orthographic information in L2 spoken word
recognition depends on proficiency in L2.
PMID- 27512382
TI - Macrocognition through the Multiscale Enaction Model (MEM) Lens: Identification
of a Blind Spot of Macrocognition Research.
PMID- 27512383
TI - Obesity, Cardiovascular Fitness, and Inhibition Function: An Electrophysiological
Study.
AB - The purpose of the present study was to examine how obesity and cardiovascular
fitness are associated with the inhibition aspect of executive function from
behavioral and electrophysiological perspectives. One hundred college students,
aged 18-25 years, were categorized into four groups of equal size on the basis of
body mass index and cardiovascular fitness: a normal-weight and high-fitness (NH)
group, an obese-weight and high-fitness (OH) group, a normal-weight and low
fitness (NL) group, and an obese-weight and low-fitness (OL) group. Behavioral
measures of response time and number of errors, as well as event-related
potential measures of P3 and N1, were assessed during the Stroop Task. The
results revealed that, in general, the NH group exhibited shorter response times
and larger P3 amplitudes relative to the NL and OL groups, wherein the OL group
exhibited the longest response time in the incongruent condition. No group
differences in N1 indices were also revealed. These findings suggest that the
status of being both normal weight and having high cardiovascular fitness is
associated with better behavioral and later stages of electrophysiological
indices of cognitive function.
PMID- 27512384
TI - Links between the Brain and Retina: The Effects of Cigarette Smoking-Induced Age
Related Changes in Alzheimer's Disease and Macular Degeneration.
PMID- 27512385
TI - Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers.
AB - The growth factor progranulin has emerged in recent years as a critical regulator
of transformation in several cancer models, including breast cancer,
glioblastomas, leukemias, and hepatocellular carcinomas. Several laboratories,
including ours, have also demonstrated an important role of progranulin in
several genitourinary cancers, including ovarian, endometrial, cervical,
prostate, and bladder tumors, where progranulin acts as an autocrine growth
factor thereby modulating motility and invasion of transformed cells. In this
review, we will focus on the mechanisms of action and regulation of progranulin
signaling in genitourinary cancers with a special emphasis on prostate and
bladder tumors.
PMID- 27512386
TI - Changes in Skeletal Integrity and Marrow Adiposity during High-Fat Diet and after
Weight Loss.
AB - The prevalence of obesity has continued to rise over the past three decades
leading to significant increases in obesity-related medical care costs from
metabolic and non-metabolic sequelae. It is now clear that expansion of body fat
leads to an increase in inflammation with systemic effects on metabolism. In
mouse models of diet-induced obesity, there is also an expansion of bone marrow
adipocytes. However, the persistence of these changes after weight loss has not
been well described. The objective of this study was to investigate the impact of
high-fat diet (HFD) and subsequent weight loss on skeletal parameters in C57Bl6/J
mice. Male mice were given a normal chow diet (ND) or 60% HFD at 6 weeks of age
for 12, 16, or 20 weeks. A third group of mice was put on HFD for 12 weeks and
then on ND for 8 weeks to mimic weight loss. After these dietary challenges, the
tibia and femur were removed and analyzed by micro computed-tomography for bone
morphology. Decalcification followed by osmium staining was used to assess bone
marrow adiposity, and mechanical testing was performed to assess bone strength.
After 12, 16, or 20 weeks of HFD, mice had significant weight gain relative to
controls. Body mass returned to normal after weight loss. Marrow adipose tissue
(MAT) volume in the tibia increased after 16 weeks of HFD and persisted in the 20
week HFD group. Weight loss prevented HFD-induced MAT expansion. Trabecular bone
volume fraction, mineral content, and number were decreased after 12, 16, or 20
weeks of HFD, relative to ND controls, with only partial recovery after weight
loss. Mechanical testing demonstrated decreased fracture resistance after 20
weeks of HFD. Loss of mechanical integrity did not recover after weight loss. Our
study demonstrates that HFD causes long-term, persistent changes in bone quality,
despite prevention of marrow adipose tissue accumulation, as demonstrated through
changes in bone morphology and mechanical strength in a mouse model of diet
induced obesity and weight loss.
PMID- 27512387
TI - The Role of gsp Mutations on the Development of Adrenocortical Tumors and Adrenal
Hyperplasia.
AB - Somatic GNAS point mutations, commonly known as gsp mutations, are involved in
the pathogenesis of McCune-Albright syndrome (MAS) and have also been described
in autonomous hormone-producing tumors, such as somatotropinoma, corticotrophoma,
thyroid cancer, ovarian and testicular Leydig cell tumors, and primary
macronodular adrenocortical hyperplasia (PMAH) (1-3). The involvement of gsp
mutations in adrenal tumors was first described by Lyons et al. Since then,
several studies have detected the presence of gsp mutations in adrenal tumors,
but none of them could explain its presence along or the mechanism that leads to
tumor formation and hormone hypersecretion. As a result, the molecular
pathogenesis of the majority of sporadic adrenocortical tumors remains unclear
(3). PMAH has also been reported with gsp somatic mutations in a few cases.
Fragoso et al. identified two distinct gsp somatic mutations affecting arginine
residues on codon 201 of GNAS in a few patients with PMAH who lacked any features
or manifestations of MAS. Followed by this discovery, other studies have
continued looking for gsp mutations based on strong prior evidence demonstrating
that increased cAMP signaling is sufficient for cell proliferation and cortisol
production (2, 4). With consideration for the previously reported findings, we
conjecture that although somatic activating mutations in GNAS are a rare
molecular event, these mutations could probably be sufficient to induce the
development of macronodule hyperplasia and variable cortisol secretion. In this
manuscript, we revised the presence of gsp mutations associated with adrenal
cortical tumors and hyperplasia.
PMID- 27512388
TI - An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved
Pharmacologic Properties.
AB - We are developing an orally available small-molecule, allosteric TSH receptor
(TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The
agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture
containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many
drugs exhibit different pharmacologic properties, we assessed the properties of
E1 and E2. We separated the two enantiomers by chiral chromatography and
determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2
were shown to bind differently to a homology model of the transmembrane domain of
TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was,
therefore, predicted to be more potent than E1. In HEK293 cells expressing human
TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production,
but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2
(EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary
cultures of human thyrocytes, C2, E1, and E2 stimulated increases in
thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter
mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2
stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8
fold above basal level, whereas E1 did not have an effect. C2 stimulated an
increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal
levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels
comparable to recombinant human TSH (rhTSH, Thyrogen((r))). Thus, E2 is more
effective than either C2 or E1 in stimulating thyroid function and as efficacious
as rhTSH in vivo. E2 represents the next step toward developing an oral drug for
patients with thyroid cancer.
PMID- 27512389
TI - Genomic and Transcriptomic Resolution of Organic Matter Utilization Among Deep
Sea Bacteria in Guaymas Basin Hydrothermal Plumes.
AB - Microbial chemosynthesis within deep-sea hydrothermal vent plumes is a regionally
important source of organic carbon to the deep ocean. Although
chemolithoautotrophs within hydrothermal plumes have attracted much attention, a
gap remains in understanding the fate of organic carbon produced via
chemosynthesis. In the present study, we conducted shotgun metagenomic and
metatranscriptomic sequencing on samples from deep-sea hydrothermal vent plumes
and surrounding background seawaters at Guaymas Basin (GB) in the Gulf of
California. De novo assembly of metagenomic reads and binning by tetranucleotide
signatures using emergent self-organizing maps (ESOM) revealed 66 partial and
nearly complete bacterial genomes. These bacterial genomes belong to 10 different
phyla: Actinobacteria, Bacteroidetes, Chloroflexi, Deferribacteres, Firmicutes,
Gemmatimonadetes, Nitrospirae, Planctomycetes, Proteobacteria, Verrucomicrobia.
Although several major transcriptionally active bacterial groups
(Methylococcaceae, Methylomicrobium, SUP05, and SAR324) displayed methanotrophic
and chemolithoautotrophic metabolisms, most other bacterial groups contain genes
encoding extracellular peptidases and carbohydrate metabolizing enzymes with
significantly higher transcripts in the plume than in background, indicating they
are involved in degrading organic carbon derived from hydrothermal
chemosynthesis. Among the most abundant and active heterotrophic bacteria in deep
sea hydrothermal plumes are Planctomycetes, which accounted for seven genomes
with distinct functional and transcriptional activities. The Gemmatimonadetes and
Verrucomicrobia also had abundant transcripts involved in organic carbon
utilization. These results extend our knowledge of heterotrophic metabolism of
bacterial communities in deep-sea hydrothermal plumes.
PMID- 27512390
TI - Characterization of Chemosynthetic Microbial Mats Associated with Intertidal
Hydrothermal Sulfur Vents in White Point, San Pedro, CA, USA.
AB - The shallow-sea hydrothermal vents at White Point (WP) in Palos Verdes on the
southern California coast support microbial mats and provide easily accessed
settings in which to study chemolithoautotrophic sulfur cycling. Previous studies
have cultured sulfur-oxidizing bacteria from the WP mats; however, almost nothing
is known about the in situ diversity and activity of the microorganisms in these
habitats. We studied the diversity, micron-scale spatial associations and
metabolic activity of the mat community via sequence analysis of 16S rRNA and
aprA genes, fluorescence in situ hybridization (FISH) microscopy and sulfate
reduction rate (SRR) measurements. Sequence analysis revealed a diverse group of
bacteria, dominated by sulfur cycling gamma-, epsilon-, and deltaproteobacterial
lineages such as Marithrix, Sulfurovum, and Desulfuromusa. FISH microscopy
suggests a close physical association between sulfur-oxidizing and sulfur
reducing genotypes, while radiotracer studies showed low, but detectable, SRR.
Comparative 16S rRNA gene sequence analyses indicate the WP sulfur vent microbial
mat community is similar, but distinct from other hydrothermal vent communities
representing a range of biotopes and lithologic settings. These findings suggest
a complete biological sulfur cycle is operating in the WP mat ecosystem mediated
by diverse bacterial lineages, with some similarity with deep-sea hydrothermal
vent communities.
PMID- 27512391
TI - Diet Diversity Is Associated with Beta but not Alpha Diversity of Pika Gut
Microbiota.
AB - Wild mammals often consume different food sources as they become geographical
available. This change in diet composition is likely to influence the gut
microbial community, yet it remains unclear what the relationship looks like
particularly in small herbivores-under natural conditions. We used DNA sequencing
approaches to characterize the diet composition and gut microbial community of
wild plateau pikas (Ochotona curzoniae) collected from three altitudes. We tested
if diet and gut microbiota composition changes across altitudes, and the
relationship between diet diversity and gut microbiota diversity. Our results
showed that altitude significantly influences the composition of diet and gut
microbial communities. Notably, the alpha diversity (Shannon diversity and
observed OTUs) of individual diet was not significantly correlated with that of
gut microbiota, whereas the beta diversity (Jaccard and Bray-Curtis
dissimilarity) of diet was positively correlated with that of gut microbiota. Our
study is the first time to highlight the relationship between diet and gut
microbiota composition in wild pikas on the Qinghai-Tibet Plateau. It suggests
that the species richness within individual gut microbiota does not linearly
increase with diet diversity, whereas those individuals that are more similar in
diet composition harbor more similar gut microbiota.
PMID- 27512393
TI - Corrigendum: Food Allergy and Helicobacter pylori Infection: A Systematic Review.
AB - [This corrects the article on p. 368 in vol. 7, PMID: 27047479.].
PMID- 27512392
TI - Cystic Fibrosis Isolates of Pseudomonas aeruginosa Retain Iron-Regulated
Antimicrobial Activity against Staphylococcus aureus through the Action of
Multiple Alkylquinolones.
AB - Cystic fibrosis (CF) is a hereditary disease that predisposes individuals to
pulmonary dysfunction and chronic infections. Early infection of the CF lung with
Staphylococcus aureus is common, while Pseudomonas aeruginosa becomes dominant as
disease progresses. Emergence of P. aeruginosa likely depends on the action of
multiple 2-alkyl-4-(1H)-quinolones (AQ) secreted by this organism. We recently
showed that antimicrobial activity against S. aureus is enhanced by iron
depletion and is dependent upon multiple AQ metabolites. Two of these AQs, the
Pseudomonas quinolone signal [PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone] and 2
heptyl-4-hydroxyquinoline (HHQ), are quorum sensing molecules that activate the
expression of multiple microbicidal factors. Here we show for the first time that
HHQ also exhibits innate antimicrobial activity against S. aureus. We further
show that iron depletion potentiates the antistaphylococcal activity of HHQ, as
well as 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), another AQ that functions as
a cytochrome B inhibitor. Notably, we found that deletion of the genes for the
terminal biosynthetic steps for either PQS or HQNO results in overproduction of
the HHQ intermediate, likely maintaining the ability of these mutants to mediate
antimicrobial activity. Compensatory increases in HHQ were also observed in PQS
deficient CF isolates, which also retained the ability to mediate iron-regulated
antimicrobial activity against S. aureus. These studies demonstrate that iron
regulated antimicrobial activity of P. aeruginosa against S. aureus is due to the
cumulative effects of multiple AQ metabolites, both the production and activity
of which are modulated by environmental iron levels.
PMID- 27512394
TI - Editorial: Role of HLA and KIR in Viral Infections.
PMID- 27512395
TI - Genome-Wide Association Study Identifies Candidate Genes for Starch Content
Regulation in Maize Kernels.
AB - Kernel starch content is an important trait in maize (Zea mays L.) as it accounts
for 65-75% of the dry kernel weight and positively correlates with seed yield. A
number of starch synthesis-related genes have been identified in maize in recent
years. However, many loci underlying variation in starch content among maize
inbred lines still remain to be identified. The current study is a genome-wide
association study that used a set of 263 maize inbred lines. In this panel, the
average kernel starch content was 66.99%, ranging from 60.60 to 71.58% over the
three study years. These inbred lines were genotyped with the SNP50 BeadChip
maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population
structure was controlled by a mixed linear model (MLM) as implemented in the
software package TASSEL. After the statistical analyses, four SNPs were
identified as significantly associated with starch content (P <= 0.0001), among
which one each are located on chromosomes 1 and 5 and two are on chromosome 2.
Furthermore, 77 candidate genes associated with starch synthesis were found
within the 100-kb intervals containing these four QTLs, and four highly
associated genes were within 20-kb intervals of the associated SNPs. Among the
four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437)
is known as an important regulator of kernel starch content. The identified SNPs,
QTLs, and candidate genes may not only be readily used for germplasm improvement
by marker-assisted selection in breeding, but can also elucidate the genetic
basis of starch content. Further studies on these identified candidate genes may
help determine the molecular mechanisms regulating kernel starch content in maize
and other important cereal crops.
PMID- 27512396
TI - Genome-Wide Association Study Provides Insight into the Genetic Control of Plant
Height in Rapeseed (Brassica napus L.).
AB - Plant height is a key morphological trait of rapeseed. In this study, we measured
plant height of a rapeseed population across six environments. This population
contains 476 inbred lines representing the major Chinese rapeseed genepool and 44
lines from other countries. The 60K Brassica Infinium(r) SNP array was utilized
to genotype the association panel. A genome-wide association study (GWAS) was
performed via three methods, including a robust, novel, nonparametric Anderson
Darling (A-D) test. Consequently, 68 loci were identified as significantly
associated with plant height (P < 5.22 * 10(-5)), and more than 70% of the loci
(48) overlapped the confidence intervals of reported QTLs from nine mapping
populations. Moreover, 24 GWAS loci were detected with selective sweep signals,
which reflected the signatures of historical semi-dwarf breeding. In the linkage
disequilibrium (LD) decay range up-and downstream of 65 loci (r (2) > 0.1), we
found plausible candidates orthologous to the documented Arabidopsis genes
involved in height regulation. One significant association found by GWAS
colocalized with the established height locus BnRGA in rapeseed. Our results
provide insights into the genetic basis of plant height in rapeseed and may
facilitate marker-based breeding.
PMID- 27512397
TI - Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus
urticae Feeding on the Host Plant.
AB - The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is
one of the most polyphagous herbivores feeding on cell contents of over 1100
plant species including more than 150 crops. It is being established as a model
for chelicerate herbivores with tools that enable tracking of reciprocal
responses in plant-spider mite interactions. However, despite their important
pest status and a growing understanding of the molecular basis of interactions
with plant hosts, knowledge of the way mites interface with the plant while
feeding and the plant damage directly inflicted by mites is lacking. Here,
utilizing histology and microscopy methods, we uncovered several key features of
T. urticae feeding. By following the stylet path within the plant tissue, we
determined that the stylet penetrates the leaf either in between epidermal
pavement cells or through a stomatal opening, without damaging the epidermal
cellular layer. Our recordings of mite feeding established that duration of the
feeding event ranges from several minutes to more than half an hour, during which
time mites consume a single mesophyll cell in a pattern that is common to both
bean and Arabidopsis plant hosts. In addition, this study determined that leaf
chlorotic spots, a common symptom of mite herbivory, do not form as an immediate
consequence of mite feeding. Our results establish a cellular context for the
plant-spider mite interaction that will support our understanding of the
molecular mechanisms and cell signaling associated with spider mite feeding.
PMID- 27512398
TI - Shallow Whole Genome Sequencing for the Assembly of Complete Chloroplast Genome
Sequence of Arachis hypogaea L.
PMID- 27512399
TI - Analysis of Drought-Induced Proteomic and Metabolomic Changes in Barley (Hordeum
vulgare L.) Leaves and Roots Unravels Some Aspects of Biochemical Mechanisms
Involved in Drought Tolerance.
AB - In this study, proteomic and metabolomic changes in leaves and roots of two
barley (Hordeum vulgare L.) genotypes, with contrasting drought tolerance,
subjected to water deficit were investigated. Our two-dimensional electrophoresis
(2D-PAGE) combined with matrix-assisted laser desorption time of flight mass
spectrometry (MALDI-TOF and MALDI-TOF/TOF) analyses revealed 121 drought
responsive proteins in leaves and 182 in roots of both genotypes. Many of the
identified drought-responsive proteins were associated with processes that are
typically severely affected during water deficit, including photosynthesis and
carbon metabolism. However, the highest number of identified leaf and root
proteins represented general defense mechanisms. In addition, changes in the
accumulation of proteins that represent processes formerly unassociated with
drought response, e.g., phenylpropanoid metabolism, were also identified. Our
tandem gas chromatography - time of flight mass spectrometry (GC/MS TOF) analyses
revealed approximately 100 drought-affected low molecular weight compounds
representing various metabolite types with amino acids being the most affected
metabolite class. We compared the results from proteomic and metabolomic analyses
to search for existing relationship between these two levels of molecular
organization. We also uncovered organ specificity of the observed changes and
revealed differences in the response to water deficit of drought susceptible and
tolerant barley lines. Particularly, our results indicated that several of
identified proteins and metabolites whose accumulation levels were increased with
drought in the analyzed susceptible barley variety revealed elevated constitutive
accumulation levels in the drought-resistant line. This may suggest that
constitutive biochemical predisposition represents a better drought tolerance
mechanism than inducible responses.
PMID- 27512400
TI - Circadian Oscillation of the Lettuce Transcriptome under Constant Light and Light
Dark Conditions.
AB - Although, the circadian clock is a universal biological system in plants and it
orchestrates important role of plant production such as photosynthesis, floral
induction and growth, there are few such studies on cultivated species. Lettuce
is one major cultivated species for both open culture and plant factories and
there is little information concerning its circadian clock system. In addition,
most of the relevant genes have not been identified. In this study, we detected
circadian oscillation in the lettuce transcriptome using time-course RNA
sequencing (RNA-Seq) data. Constant light (LL) and light-dark (LD) conditions
were used to detect circadian oscillation because the circadian clock has some
basic properties: one is self-sustaining oscillation under constant light and
another is entrainment to environmental cycles such as light and temperature. In
the results, 215 contigs were detected as common oscillating contigs under both
LL and LD conditions. The 215 common oscillating contigs included clock gene-like
contigs CCA1 (CIRCADIAN CLOCK ASSOCIATED 1)-like, TOC1 (TIMING OF CAB EXPRESSION
1)-like and LHY (LATE ELONGATED HYPOCOTYL)-like, and their expression patterns
were similar to those of Arabidopsis. Functional enrichment analysis by GO (gene
ontology) Slim and GO Fat showed that the GO terms of response to light stimulus,
response to stress, photosynthesis and circadian rhythms were enriched in the 215
common oscillating contigs and these terms were actually regulated by circadian
clocks in plants. The 215 common oscillating contigs can be used to evaluate
whether the gene expression pattern related to photosynthesis and optical
response performs normally in lettuce.
PMID- 27512401
TI - Role of Silicon Counteracting Cadmium Toxicity in Alfalfa (Medicago sativa L.).
AB - Cadmium (Cd) is one of the most phytotoxic elements causing an agricultural
problem and human health hazards. This work investigates whether and how silicon
(Si) ameliorates Cd toxicity in Alfalfa. The addition of Si in Cd-stressed plants
caused significant improvement in morpho-physiological features as well as total
protein and membrane stability, indicating that Si does have critical roles in Cd
detoxification in Alfalfa. Furthermore, Si supplementation in Cd-stressed plants
showed a significant decrease in Cd and Fe concentrations in both roots and
shoots compared with Cd-stressed plants, revealing that Si-mediated tolerance to
Cd stress is associated with Cd inhibition in Alfalfa. Results also showed no
significant changes in the expression of two metal chelators [MsPCS1
(phytochelatin synthase) and MsMT2 (metallothionein)] and PC (phytochelatin)
accumulation, indicating that there may be no metal sequestration or change in
metal sequestration following Si application under Cd stress in Alfalfa. We
further performed a targeted study on the effect of Si on Fe uptake mechanisms.
We observed the consistent reduction in Fe reductase activity, expression of Fe
related genes [MsIRT1 (Fe transporter), MsNramp1 (metal transporter) and OsFRO1
(ferric chelate reductase] and Fe chelators (citrate and malate) by Si
application to Cd stress in roots of Alfalfa. These results support that limiting
Fe uptake through the down-regulation of Fe acquisition mechanisms confers Si
mediated alleviation of Cd toxicity in Alfalfa. Finally, an increase of catalase,
ascorbate peroxidase, and superoxide dismutase activities along with elevated
methionine and proline subjected to Si application might play roles, at least in
part, to reduce H2O2 and to provide antioxidant defense against Cd stress in
Alfalfa. The study shows evidence of the effect of Si on alleviating Cd toxicity
in Alfalfa and can be further extended for phytoremediation of Cd toxicity in
plants.
PMID- 27512402
TI - Physiological Degradation of Pectin in Papaya Cell Walls: Release of Long Chains
Galacturonans Derived from Insoluble Fractions during Postharvest Fruit Ripening.
AB - Papaya (Carica papaya L.) is a fleshy fruit that presents a rapid pulp softening
during ripening. However, the timeline on how papaya pectinases act in
polysaccharide solubilization and the consequent modification of the cell wall
fractions during ripening is still not clear. In this work, the gene expression
correlations between, on one hand, 16 enzymes potentially acting during papaya
cell wall disassembling and, on the other hand, the monosaccharide composition of
cell wall fractions during papaya ripening were evaluated. In order to explain
differences in the ripening of papaya samplings, the molecular mass distribution
of polysaccharides from water-soluble and oxalate-soluble fractions (WSF and OSF,
respectively), as well as the oligosaccharide profiling from the WSF fraction,
were evaluated by high performance size exclusion chromatography coupled to a
refractive index detector and high performance anion-exchange chromatography
coupled to pulse amperometric detection analyses, respectively. Results showed
that up-regulated polygalacturonase and beta-galactosidase genes were positively
correlated with some monosaccharide profiles. In addition, an overall increase in
the retention time of high molecular weight (HMW) and low molecular weight (LMW)
polysaccharides in WSF and OSF was shown. The apparent disappearance of one HMW
peak of the OSF may result from the conversion of pectin that were crosslinked
with calcium into more soluble forms through the action of PGs, which would
increase the solubilization of polysaccharides by lowering their molecular
weight. Thus, the results allowed us to propose a detailed process of papaya cell
wall disassembling that would affect sensorial properties and post-harvesting
losses of this commercially important fruit.
PMID- 27512403
TI - Plant Abiotic Stress Challenges from the Changing Environment.
PMID- 27512404
TI - Fundamental Issues of Melatonin-Mediated Stress Signaling in Plants.
AB - As a widely known hormone in animals, melatonin (N-acetyl-5-methoxytryptamine)
has been more and more popular research topic in various aspects of plants. To
summarize the these recent advances, this review focuses on the regulatory
effects of melatonin in plant response to multiple abiotic stresses including
salt, drought, cold, heat and oxidative stresses and biotic stress such as
pathogen infection. We highlight the changes of endogenous melatonin levels under
stress conditions, and the extensive metabolome, transcriptome, and proteome
reprogramming by exogenous melatonin application. Moreover, melatonin-mediated
stress signaling and underlying mechanism in plants are extensively discussed.
Much more is needed to further study in detail the mechanisms of melatonin
mediated stress signaling in plants.
PMID- 27512405
TI - Cellular Recycling of Proteins in Seed Dormancy Alleviation and Germination.
AB - Each step of the seed-to-seed cycle of plant development including seed
germination is characterized by a specific set of proteins. The continual renewal
and/or replacement of these biomolecules are crucial for optimal plant
adaptation. As proteins are the main effectors inside the cells, their levels
need to be tightly regulated. This is partially achieved by specific proteolytic
pathways via multicatalytic protease complexes defined as 20S and 26S
proteasomes. In plants, the 20S proteasome is responsible for degradation of
carbonylated proteins, while the 26S being a part of ubiquitin-proteasome pathway
is known to be involved in proteolysis of phytohormone signaling regulators. On
the other hand, the role of translational control of plant development is also
well-documented, especially in the context of pollen tube growth and light
signaling. Despite the current progress that has been made in seed biology, the
sequence of cellular events that determine if the seed can germinate or not are
still far from complete understanding. The role and mechanisms of regulation of
proteome composition during processes occurring in the plant's photosynthetic
tissues have been well-characterized since many years, but in non-photosynthetic
seeds it has emerged as a tempting research task only since the last decade. This
review discusses the recent discoveries providing insights into the role of
protein turnover in seed dormancy alleviation, and germination, with a focus on
the control of translation and proteasomal proteolysis. The presented novel data
of translatome profiling in seeds highlighted that post-transcriptional
regulation of germination results from a timely regulated initiation of
translation. In addition, the importance of 26S proteasome in the degradation of
regulatory elements of cellular signaling and that of the 20S complex in
proteolysis of specific carbonylated proteins in hormonal- and light-dependent
processes occurring in seeds is discussed. Based on the current knowledge the
model of cellular recycling of proteins in germinating seeds is also proposed.
PMID- 27512406
TI - Limitation of Grassland Productivity by Low Temperature and Seasonality of
Growth.
AB - The productivity of temperate grassland is limited by the response of plants to
low temperature, affecting winter persistence and seasonal growth rates. During
the winter, the growth of perennial grasses is restricted by a combination of low
temperature and the lack of available light, but during early spring low ground
temperature is the main limiting factor. Once temperature increases, growth is
stimulated, resulting in a peak in growth in spring before growth rates decline
later in the season. Growth is not primarily limited by the ability to
photosynthesize, but controlled by active regulatory processes that, e.g., enable
plants to restrict growth and conserve resources for cold acclimation and winter
survival. An insufficient ability to cold acclimate can affect winter
persistence, thereby also reducing grassland productivity. While some mechanistic
knowledge is available that explains how low temperature limits plant growth, the
seasonal mechanisms that promote growth in response to increasing spring
temperatures but restrict growth later in the season are only partially
understood. Here, we assess the available knowledge of the physiological and
signaling processes that determine growth, including hormonal effects, on
cellular growth and on carbohydrate metabolism. Using data for grass growth in
Ireland, we identify environmental factors that limit growth at different times
of the year. Ideas are proposed how developmental factors, e.g., epigenetic
changes, can lead to seasonality of the growth response to temperature. We also
discuss perspectives for modeling grass growth and breeding to improve grassland
productivity in a changing climate.
PMID- 27512407
TI - High-fat but not sucrose intake is essential for induction of dyslipidemia and
non-alcoholic steatohepatitis in guinea pigs.
AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are
closely related. Diet plays an important role in the progression of these
diseases, but the role of specific dietary components is not completely
understood. Therefore, we investigated the role of dietary sucrose and
fat/cholesterol on the development of dyslipidemia and NAFLD. METHODS: Seventy
female guinea pigs were block-randomized (based on weight) into five groups and
fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 %
fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high
fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a
high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 %
cholesterol) for 16 and 25 weeks. RESULTS: All three high-fat diets induced
dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001),
LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to
this, plasma triglycerides were increased in control and vHS compared to high-fat
fed animals (p < 0.01), while circulating levels of free fatty acids were even
between groups. Histological evaluation of liver sections revealed non-alcoholic
steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in
high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and
cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and
aspartate aminotransferase (p < 0.01) compared to control and vHS. CONCLUSION:
Collectively, our results suggest that intake of fat and cholesterol, but not
sucrose, are the main factors driving the development and progression of
dyslipidemia and NAFLD/NASH.
PMID- 27512408
TI - Understanding Counterfactuality: A Review of Experimental Evidence for the Dual
Meaning of Counterfactuals.
AB - Cognitive and linguistic theories of counterfactual language comprehension assume
that counterfactuals convey a dual meaning. Subjunctive-counterfactual
conditionals (e.g., 'If Tom had studied hard, he would have passed the test')
express a supposition while implying the factual state of affairs (Tom has not
studied hard and failed). The question of how counterfactual dual meaning plays
out during language processing is currently gaining interest in
psycholinguistics. Whereas numerous studies using offline measures of language
processing consistently support counterfactual dual meaning, evidence coming from
online studies is less conclusive. Here, we review the available studies that
examine online counterfactual language comprehension through behavioural
measurement (self-paced reading times, eye-tracking) and neuroimaging
(electroencephalography, functional magnetic resonance imaging). While we argue
that these studies do not offer direct evidence for the online computation of
counterfactual dual meaning, they provide valuable information about the way
counterfactual meaning unfolds in time and influences successive information
processing. Further advances in research on counterfactual comprehension require
more specific predictions about how counterfactual dual meaning impacts
incremental sentence processing.
PMID- 27512410
TI - Editorial resolutions.
PMID- 27512409
TI - A review of the infection-associated cancers in North African countries.
AB - Cancer is typically classified as a leading non-communicable disease; however,
infectious agents, such as Helicobacter pylori (H. pylori), hepatitis B virus
(HBV), hepatitis C virus (HCV) and human papilloma virus (HPV), contribute
significantly to the pathogenesis of various cancers. Less developed countries,
including countries of the North African (NA) region, endure the highest burden
of infection-related cancers. The five most common infection-associated cancers
in NA in order of incidence are bladder cancer, cervical cancer, liver cancer,
stomach cancer, and nasopharyngeal carcinoma. This review aims to outline the
epidemiologic pattern of infection-associated cancers in five NA countries
(namely: Morocco, Algeria, Tunisia, Libya and Egypt) highlighting the
similarities and differences across the region. The present study employed an
initial literature review of peer-reviewed articles selected from PubMed,
ScienceDirect and World Health Organization (WHO) databases based on key word
searches without restriction on publication dates. Original research articles and
reports written in French, as well as data from institutional reports and
regional meeting abstracts were also included in this extensive review. Egypt,
Libya, Tunisia, Algeria and Morocco were selected to be the focus of this review.
PMID- 27512411
TI - Update on vitamin D: More than just a nutrient.
AB - An increasing number of pregnancy complications have been ascribed or at least
associated with vitamin D deficiency. Vitamin D has undergone a metamorphosis
from nutrient to hormone and more recently has been recognised to have broader
biological relevance. This includes potential immunogenic, oncogenic and
metabolic actions. This review outlines the roles of vitamin D, the problems in
accurate measurement and determining normal ranges and how this is important in
an understanding of vitamin D in normal and abnormal pregnancy.
PMID- 27512413
TI - Amniotic fluid embolism: the known and not known.
AB - Amniotic fluid embolism was first recognized in 1926, in a Brazilian journal case
report, on the basis of large amounts of fetal material in the maternal pulmonary
vasculature at autopsy. The first English language description appeared in 1941
and consisted of eight parturients dying suddenly in which, once again, fetal
material was seen in the pulmonary vasculature. A control group of 34 pregnant
women dying of other recognized causes did not have fetal material in their
lungs. The incidence of recognized, serious illness is on the order of two to
eight per 100,000, with a mortality rate ranging from 13% to 35%. The diagnosis
rests largely on one or more of four clinical signs: circulatory collapse,
respiratory distress, coagulopathy, and seizures/ coma. The only confirmatory
laboratory test remains autopsy findings although serum tests for fetal antigen,
insulin-like growth factor binding protein-1, and complement are currently being
investigated. One of the paradoxes of diagnosis is that fetal material in the
pulmonary circulation at autopsy is specific for amniotic fluid embolism, while
the same finding in the living is not. The mechanism of disease remains uncertain
although the best available evidence suggests that complement activation might
have a role. In contrast, mast cell degranulation probably is not a mechanism, so
amniotic fluid embolism is not an anaphylaxis or anaphylactoid reaction as has
been occasionally suggested. Perhaps the greatest unknown is not why 1 in 50,000
pregnant women develop what appears to be an immune response to their fetus, but
rather why the other 49,999 do not?
PMID- 27512415
TI - Response to fifty grams oral glucose challenge test and pattern of preceding
fasting plasma glucose in normal pregnant Nigerians.
AB - BACKGROUND: Diabetes mellitus in pregnancy has profound implications for the baby
and mother and thus active screening for this is desirable. METHOD: Fifty grams
oral glucose challenge test was administered after obtaining consent to 222 women
in good health with singleton pregnancies without diabetes mellitus at 24 to 28
weeks gestation after an overnight fast. Venous blood sample was obtained before
and 1 hour after the glucose load. A diagnostic 3-hour 100 g oral glucose
tolerance test was subsequently performed in all. RESULTS: Two hundred and ten
women had a normal response to oral glucose tolerance test i.e. venous plasma
glucose below these cut-off levels: fasting 95 mg/dl (5.3 mmol/l), 1 hour 180
mg/dl (10.0 mmol/l), 2 hours 155 mg/dl (8.6 mmol/l) and 3 hours 140 mg/dl (7.8
mmol/l), while 12 were found to have gestational diabetes mellitus and were
subsequently excluded from the study. They were appropriately managed. The mean
maternal age was 30.9 +/- 4.1 years (range 19 to 45 years) and the mean parity
was 1.2 +/- 1.1 (range 0 to 5). The mean fasting plasma glucose was 74.5 +/- 11.5
mg/dl (range 42 to 117 mg/dl), while the mean plasma glucose 1 hour after 50 g
glucose challenge test was 115.3 +/- 19.1 mg/dl (range 56 to 180 mg/dl).
CONCLUSIONS: The mean fasting plasma glucose in normal pregnant Nigerians was
74.5 +/- 11.5 mg/dl (range 42 to 117 mg/dl). There is a need to re-appraise and
possibly review downwards the World Health Organization fasting plasma glucose
diagnostic criteria in pregnant Nigerians for better detection of gestational
diabetes mellitus. Pregnant women with venous plasma glucose greater than 153.5
mg/dl (8.5 mmol/l) 1 hour after 50 g glucose challenge test are strongly
recommended for diagnostic test of gestational diabetes mellitus.
PMID- 27512414
TI - The importance of visceral fat mass in obese pregnant women and relation with
pregnancy outcomes.
AB - BACKGROUND: Maternal obesity is a well established risk factor for gestational
diabetes but it is not known if the pattern of maternal fat distribution predicts
adverse pregnancy outcomes. METHODS: Body composition was assessed by
bioimpedance using Inbody 720(r) in 302 consecutive obese pregnant women
attending a weight management clinic. The relation of visceral fat mass and total
percentage body fat with the development of gestational diabetes and perinatal
outcomes was evaluated. RESULTS: Women developing gestational diabetes (Group 1;
n = 72) were older, had higher body mass indices and greater central obesity
(waist:hip ratio, visceral fat mass) compared with those remaining
normoglycaemic. Visceral fat mass, but not percentage body fat, correlated with
fasting glucose in all patients (r = 0.2, p < 0.001) and particularly those in
Group 1 (r = 0.35, p = 0.002). Visceral fat mass, but not percentage body fat,
also correlated strongly with glycaemia, particularly in Group 1 (r = 0.47, p <
0.0001). Visceral fat mass also showed a weak but significant correlation with
baby weight (r = 0.17, p = 0.01). DISCUSSION: Central obesity, as assessed by
early pregnancy waist:hip ratio and particularly by visceral fat mass, is a
predictor of gestational diabetes in addition to classical risk factors and may
help identify those obese patients at increased risk of complications.
PMID- 27512412
TI - Timing of delivery in women with diabetes in pregnancy.
AB - The incidence of both gestational and pre-gestational diabetes is increasing
worldwide. The main cause of this increase is likely the concomitant increase in
the incidence of global obesity, but in the case of gestational diabetes, changes
in the diagnostic criteria are also a contributing factor. The adverse outcomes
associated with pre-gestational diabetes are well known and have led clinicians
to implement various strategies that include increased fetal surveillance and
induction of labour at various gestational ages. In many cases these same
strategies have been applied in clinical practice also to women with gestational
diabetes despite there being differences in the type and magnitude of perinatal
complications associated with this diagnosis. Despite the widespread application
of these clinical practices, there is a paucity of quality data in the medical
literature to guide the clinician in choosing a strategy for fetal surveillance
and timing of delivery in both gestational diabetes and pre-gestational diabetes
pregnancies. In the following review, we will discuss the rationale and
consequences of planned delivery in gestational diabetes and pre-gestational
diabetes, the evidence supporting different strategies for delivery and finally
highlight future targets for research in this area.
PMID- 27512416
TI - Pregnancy outcome and follow-up cardiac outcome in women with aortic valve
replacement.
AB - OBJECTIVES: To compare the maternal, fetal and cardiac outcomes in women who have
undergone aortic valve replacement. METHOD: Retrospective observational study of
all women with aortic valve replacement, who underwent a pregnancy (1998-2012).
Maternal-, fetal- and valve-related cardiac outcomes were assessed. RESULTS:
Thirty-two pregnancies in 16 women with aortic valve replacement (nine
bioprosthetic, six Ross and 17 mechanical) were evaluated. There were no adverse
maternal events in the bioprosthetic and Ross groups but three in the mechanical
group. Fetal loss rate was highest in the mechanical valve pregnancies (53%). One
woman in the bioprosthetic group needed valve re-operation, and one woman in the
mechanical valve group died. There was no difference in the change of Vmax over
the follow-up between the valves (p = 0.25). CONCLUSIONS: There was no difference
in deterioration between aortic valve replacements during and after pregnancy.
The highest risk of maternal and fetal complications occurred in the mechanical
valve group.
PMID- 27512417
TI - Amniotic fluid embolism: Then and now.
AB - BACKGROUND: The first case report to describe amniotic fluid embolism that
appeared in 1926 in Basil-Medico is translated from Portuguese to English. CASE:
A patient with a dead fetus for several weeks, presented in labor and died
suddenly with fetal squames evident in the maternal pulmonary vasculature at
autopsy. CONCLUSION: As can be seen from the translation, this case report is
remarkably similar in many of its features to some of the eight patients
described 15 years later in the first English language discussion of the disease
by Steiner and Luschbaugh in JAMA. An enigma presented by this first case remains
today: fetal material in the maternal pulmonary vasculature appears specific for
amniotic fluid embolism at autopsy but not in living patients.
PMID- 27512418
TI - Idiopathic granulomatous mastitis with erythema nodosum simulating breast abscess
in pregnancy: A case report.
AB - Granulomatous mastitis is a rare benign inflammatory condition of the breast and
is known to be associated with pregnancy. A 25-year-old Hispanic G2P1 at 17 weeks
gestation presented to the emergency department with findings consistent of a
breast abscess. The abscess failed to resolve with incision and drainage followed
by multiple courses of antibiotic therapy. A biopsy was then obtained and yielded
a diagnosis of granulomatous lobulitis. The patient was treated with steroids and
her symptoms resolved. Granulomatous lobulitis may present with characteristics
of various clinical entities including neoplasm or, as in this case, abscess.
Clinicians should consider a diagnosis of granulomatous mastitis in cases of
recalcitrant breast abscess.
PMID- 27512419
TI - Pregnancy outcomes in patients with severe pulmonary hypertension and Eisenmenger
syndrome treated with sildenafil monotherapy.
AB - Pregnancy outcomes in patients with pulmonary arterial hypertension have not been
documented in our local setting. In our institution, access to therapies like
nitric oxide, inhaled prostacyclin and iloprost is limited. We describe two such
women given sildenafil monotherapy between April and May 2011. Both had an atrial
septal defect complicated by Eisenmenger syndrome. Both survived - one after
elective Caesarean section for malpresentation (breech) under general
anaesthesia, the other after an assisted vaginal delivery. In addition to oral
sildenafil, both received oxygen supplementation. To date, there have been three
reported cases of pulmonary arterial hypertension in pregnancy treated with
sildenafil in combination with another drug. Our two cases demonstrate that
treatment for pulmonary arterial hypertension using sildenafil as monotherapy may
allow stabilization of the maternal condition and improve clinical outcomes for
both mother and baby. However, pregnancy is still discouraged in women with
pulmonary arterial hypertension.
PMID- 27512420
TI - A stormy and rare presentation: Eclampsia at 18 weeks of gestation.
AB - Eclampsia is an Obstetric emergency. It is uncommon in early second trimester and
an early diagnosis will aid in preventing complications. We report an unusual
case of eclampsia at an 18 weeks gestation with a good maternal outcome.
PMID- 27512421
TI - Adrenal cortical carcinoma mimicking early severe preeclampsia.
AB - Preeclampsia is a common disorder in pregnancy and may affect multiple maternal
and foetal organ systems. Less common disorders with similar features may imitate
preeclampsia though require different management strategies and with different
prognostic implications for mother and baby. We present a case of a pregnant
woman who developed severe hypertension and proteinuria in pregnancy. The early
onset of these changes prompted investigation for causes other than preeclampsia,
leading to a diagnosis of Cushing's syndrome due to stage III adrenocortical
cancer. The changes in management strategy, the importance of a multidisciplinary
approach to care, and the prognostic implications for the mother are discussed.
PMID- 27512422
TI - Fluid management: Not just a problem in preeclampsia.
PMID- 27512423
TI - Multidisciplinary meeting of minds.
PMID- 27512425
TI - Techniques to measure free-living energy expenditure during pregnancy - A guide
for clinicians and researchers.
AB - As maternal overweight and obesity increase in prevalence, the need to optimise
gestational weight gain has entered the forefront due to the well-documented poor
fetal and maternal outcomes associated with excess adipose tissue. Measurements
of changes in energy expenditure form crucial components of effective weight
management programmes, and they are also important for clarifying the energy
requirements of pregnancy. This review evaluates the primary techniques for
measuring free-living energy expenditure for use in pregnancy, with special
consideration of the dynamic physiological changes that occur in this state. The
methods that will be discussed include the doubly labelled water method, activity
recall and activity logs, heart rate monitors and motion sensors. This article
may be useful for clinicians seeking to implement active gestational weight
management by enabling advice on increases in caloric intake linked to measured
changes in energy expenditure, and for researchers studying energy metabolism in
pregnancy.
PMID- 27512424
TI - Factors determining insulin requirements in women with type 1 diabetes mellitus
during pregnancy: a review.
AB - Most women with type 1 diabetes mellitus (T1DM) have increased insulin
requirements during pregnancy. However, a minority of women have a fall in
insulin requirements. When this occurs in late gestation, it often provokes
concern regarding possible compromise of the feto-placental unit. In some
centres, this is considered as an indication for delivery, including premature
delivery. There are, however, many other factors that affect insulin requirements
in pregnancy in women with type 1 diabetes mellitus and the decline in insulin
requirements may represent a variant of normal pregnancy. If there is no
underlying pathological process, expedited delivery in these women is not
warranted and confers increased risks to the newborn. We will explore the factors
affecting insulin requirements in gestation in this review. We will also discuss
some novel concepts regarding beta-cell function in pregnancy.
PMID- 27512426
TI - A mother-baby psychiatric day hospital: History, rationale, and why perinatal
mental health is important for obstetric medicine.
AB - BACKGROUND: Women frequently experience depression, anxiety, or other mental
health concerns during pregnancy and postpartum, impacting her and her infant's
health. Patients who require management of medical conditions during the
perinatal period are even more likely to experience depression and anxiety
compared to those without comorbid medical issues. Despite the availability of
effective treatments, perinatal mental health utilization rates are strikingly
low. METHODS: To address common treatment barriers, we developed a specialized
mother-baby day hospital for women with psychiatric distress during the
peripartum. In this report, we summarize findings from 800 patient satisfaction
surveys collected from women treated at the program between 2007 and 2012.
RESULTS: Findings suggest that women are highly satisfied with the treatment
received, often noting that the inclusion of the baby in their treatment is a
highly valued feature of care. CONCLUSION: The relevance of perinatal mental
health services for patients who are followed by obstetrical medicine specialists
is discussed.
PMID- 27512427
TI - Magnesium sulfate for eclampsia prevention: Quality of care evaluation in a
tertiary centre in Quebec, Canada.
AB - BACKGROUND: The current Canadian guidelines endorse the use of MgSO4 for
treatment of eclampsia and for prophylaxis in severe preeclampsia. Our study
aimed to audit our institution's compliance regarding these guidelines. METHODS:
We conducted a retrospective study to evaluate MgSO4 use in: all our cases of
eclampsia since 2002, 50 cases of severe preeclampsia, and 50 cases of non-severe
preeclampsia. RESULTS: Sixty-five cases of preeclampsia were analyzed after
initial chart review. A high rate of preeclampsia severity misdiagnosis was
observed (35%, 23/65). Only 69% (25/36) of the patients correctly diagnosed with
severe preeclampsia received MgSO4; after diagnosis correction, 42% (25/59) of
the patients with severe preeclampsia received the medication. Of our eight cases
of eclampsia, none of the patients received MgSO4 before the seizure (although
three had clear indications). CONCLUSION: Given the importance of prophylactic
MgSO4 use in preventing eclampsia, we have implemented informative measures aimed
at rapidly achieving complete compliance with the national guidelines.
PMID- 27512428
TI - Haemorrhagic complications of peripartum anticoagulation: A retrospective chart
review.
AB - BACKGROUND: Women with venous thromboembolism (VTE), thrombophilias or mechanical
heart valves may require anticoagulation during pregnancy and postpartum. The
incidence of postpartum hemorrhage (PPH) in the literature is 2.9-6%, but the
rate while on anticoagulation is not well documented. AIMS: To determine the
incidence of haemorrhagic complications associated with the use of peripartum
anticoagulation, and the types and risk factors for haemorrhagic complications.
METHODS: A retrospective chart review was conducted on women who delivered at an
academic teaching hospital and received peripartum anticoagulation between
January 2000 and August 2009. Women with known bleeding disorders were excluded.
RESULTS: In total, 195 cases were identified with mean age 31.3 years and
gestational age of 37.7 weeks. Of these, 49% had a history of VTE, 21% had active
VTE in the index pregnancy, and 63% had vaginal delivery. Types of
anticoagulation used antepartum were unfractionated heparin (UFH) (43%) and low
molecular weight heparin (LMWH) (36%), with 26% receiving therapeutic doses. The
rate of haemorrhagic complications was 12.8%, with majority being PPH (80%).
Sixty percent of the PPH occurred before reintroduction of anticoagulation
postpartum. Use of therapeutic UFH antepartum was associated with increased risk
of haemorrhagic complications compared to LMWH (OR 3.08, 95% CI 0.663 - 15.03, p
= 0.183). CONCLUSION: The rate of haemorrhagic complications is higher in women
on peripartum anticoagulation compared with published incidence in unselected
obstetric populations; however, this rate is similar to our institution's
reported rates. Our findings inform clinicians about competing risks of
thrombotic and haemorrhagic complications in this population.
PMID- 27512429
TI - The effect of pregnancy on venous valve repair to the sapheno-femoral junction
for varicose veins.
AB - OBJECTIVES: Pregnancy represents a special situation where both the mechanical
and hormonal instigating factors of varicose veins are reversible with the venous
valve cusps preserved. Exostent venous valve repairs are a physiological
alternative which minimises stimulus to collateral growth (recurrence). The study
purpose was to assess the effect of pregnancy on the durability of valve repairs.
METHODS: In a prospective study of 36 limbs, 20 young females (30 +/- 4.7 years)
had an exostent implanted to the terminal valve of the saphenofemoral junction
for varicose veins. At routine long-term follow up (9.7 +/- 3.8 years), 38
pregnancies were completed (mean: 1.8, range: 1-4). The controls were a non
pregnant group of limbs (n = 386). RESULTS: At 9.7 years, the internal diameter
of the greater saphenous vein (GSV) changed from 7.8 +/- 2.8 mm preoperatively to
4.5 +/- 1.4 mm post-operatively. Recurrence was associated with reflux,
preoperative deep system and ovarian vein involvement. Pregnancy induced 33.3%
recurrences compared with non-pregnant controls (4.7%) similarly treated or 22.8%
compared with non-pregnant ablative controls. At 9.7 years, symptomatic
improvement continued with significantly better CEAP status (described later)
(31CSEAP preoperative to 6CSEAP) with no further truncal ablation (strip, laser)
required. CONCLUSIONS: Venous valve repairs can withstand the special stresses of
pregnancy. There is no need to ablate the GSV. This approach is contrary to the
traditional dictum; the treatment of varicose veins should be delayed until the
family is completed.
PMID- 27512430
TI - Who develops carpal tunnel syndrome during pregnancy: An analysis of obesity,
gestational weight gain, and parity.
AB - PURPOSE: To examine the prevalence, onset, and risk factors of carpal tunnel
syndrome during pregnancy. METHODS: Maternal electronic medical records were
linked to birth certificate records using social security number. The outcome of
carpal tunnel syndrome during pregnancy was defined as ICD9 code 354.0 given at a
prenatal visit. Chi-square, t-test, and adjusted logistic regression were
performed. RESULTS: We analyzed 17,623 prenatal visits from the Hospital of the
University of Pennsylvania from 1/2003-12/2007. Mean maternal age was 26.4 (6.5)
years, with 21% white, 69% black, and 46% overweight or obese. Ninety-one (2.8%)
mothers participated in 765 prenatal visits given a carpal tunnel syndrome
diagnosis code. Compared to mothers without carpal tunnel syndrome, mothers with
carpal tunnel syndrome were older (29.72 (5.42) versus 26.04 (6.37) years, p =
0.005), gained more weight during pregnancy (40.65 (10.13) pounds versus 34.2
(9.41) pounds, p = 0.04), and more likely to have college education (69.9% versus
44.5%, p = 0.03). Average onset (SD) of carpal tunnel syndrome was 18.1 (8.4)
weeks' gestation. CONCLUSION: Mothers with carpal tunnel syndrome had high rates
of overweight, obesity, and excessive gestational weight gain. Diagnosis of
carpal tunnel syndrome was rare but often occurred in the first and second
trimesters, earlier than the frequently reported third trimester onset seen in
literature. When looking at predictors of carpal tunnel syndrome, obese
prepregnancy body mass index (BMI >= 30 kg/m(2)) and excessive gestational weight
gain, greater than two previous live births, higher level of maternal education
and more prenatal care (>10 visits) were associated with increased risk of carpal
tunnel syndrome. Higher maternal age was not associated with carpal tunnel
syndrome diagnosis after adjusting for weight and parity, suggesting mediation by
these covariates.
PMID- 27512431
TI - Editorial.
PMID- 27512432
TI - Post partum infections: A review for the non-OBGYN.
AB - The epidemiology of infections in the puerperium (post partum period) is not well
understood and remains underestimated because surveillance systems are often
limited to the acute care setting. The most common source of persistent fever
after delivery is genital tract infection for which diagnosis remains mostly
clinical and antibiotic treatment empiric. This review will emphasize surgical
site infections (SSIs) and endometritis. Septic thrombo-phlebitis, mastitis,
urinary tract infections and rare infections will be covered in less detail.
Puerperal sepsis will not be reviewed.
PMID- 27512433
TI - Renal stones in pregnancy.
AB - Diagnosis and treatment of renal stones during pregnancy is a complex problem.
Risks to the fetus from ionising radiation and interventional procedures need to
be balanced with optimising clinical care for the mother. Management of such
patients requires a clear understanding of available options, with a
multidisciplinary team approach. In this review, we discuss the role of different
diagnostic tests including ultrasound, magnetic resonance urography, and
computerized tomography. We also provide an update on recent developments in the
treatment of renal stones during pregnancy. Expectant management remains first
line treatment. Where definitive treatment of the stone is required, new evidence
suggests that ureteroscopic stone removal may be equally safe, and possibly
better than traditional temporising procedures.
PMID- 27512434
TI - Screening, diagnosis and management of gestational diabetes mellitus: A national
survey.
AB - BACKGROUND AND METHODS: We conducted a National survey between February and June
2012 to evaluate the practices concerning screening, diagnosis and management of
Gestational Diabetes (GDM) in England. RESULTS: A total of 102/126 (80%)
maternity units responded. The National Institute of Health and Clinical
Excellence (NICE) recommended screening criteria were used by 83% of units. All
the units performed 2 h 75 g oral glucose tolerance test (OGTT) between 24 and 28
weeks. There was a wide variation in the diagnostic blood glucose values used by
different units. About 86% of units used a 2 h blood glucose value of >=7.8
mmol/l and 45% of units used fasting value >=6.1 mmol/l to diagnose GDM. Only 26%
of units advised self-monitoring of blood glucose pre meal and 1 h post-meal,
whereas 64% of units advised monitoring 2 h after the meal. Metformin was started
when women did not respond to dietary measures in 101 units (99%). Regular growth
scans every four weeks from 28 weeks onwards were performed by 99 units (97%).
Women on metformin with no complications were offered induction of labour at 38
completed weeks in 97 units (95%). 84 maternity units (82.3%) offered OGTT six
weeks postnatally. CONCLUSION: Our survey has shown consistency in screening
using the NICE criteria, use of 2 h 75 g OGTT at 24-28 weeks, in providing
dietary support, use of metformin and ultrasound for fetal growth. But there is
wide variation in the criteria used to diagnose GDM, self-monitoring of blood
glucose, induction of labour and six weeks postnatal testing.
PMID- 27512435
TI - Clinical predictors for diabetes screening in the first year postpartum after
gestational diabetes.
AB - BACKGROUND: Postpartum screening for diabetes in women with gestational diabetes
(GDM) improves with use of reminder systems. Our primary objective was to
identify predictors of diabetes screening in the first year after delivery.
METHODS: A retrospective study was performed of 556 women with GDM who received
outpatient prenatal care between 2007 and 2009. A mailed reminder system was
utilized at two sites. Rates of postpartum glucose testing at 6 and 12 months
postpartum were measured. RESULTS: Site of care and non-smoking status were
identified as the only predictors of postpartum diabetes screening (p<0.001 and p
= 0.02, respectively). Rates of OGTT completion at one year (38% vs. 19% p<0.001)
were higher in women who attended clinics with postpartum reminders. CONCLUSIONS:
The site of diabetes care in pregnancy is a major predictor of adherence to
diabetes screening postpartum. Health care delivery should be considered in the
development of strategies to increase screening rates.
PMID- 27512436
TI - A woman with familial partial lipodystrophy and the complications of her four
pregnancies.
AB - We discuss a case of a woman ultimately diagnosed with familial partial
lipodystrophy following her fourth pregnancy. In her previous pregnancies she had
numerous complications thought to be related to diabetes including recurrent
macrosomia and polyhydramnios. In her second pregnancy she underwent emergency
caesarean section for fetal tachycardia at 34 weeks' gestation. Her baby was
diagnosed with unexplained cerebral ischaemic injury and limb ischaemia requiring
amputation. Postnatally she was diagnosed with type 2 diabetes mellitus with
subsequent poor control. Very high insulin demands in this fourth pregnancy and
an unusual phenotypic appearance in the patient and her mother raised suspicion
of an underlying condition. Genetic studies confirmed the clinical diagnosis of
familial partial lipodystrophy.
PMID- 27512437
TI - Pregnancy in multiple endocrine neoplasia type 1 equals multiple complications.
AB - Multiple endocrine neoplasia type 1 (MEN 1) is a rare inherited disorder caused
by mutations in the tumour suppressor gene MEN 1. It is characterised by a
predisposition towards the development of parathyroid, anterior pituitary and
entero-pancreatic tumours. Clinically, MEN 1 is defined following development of
two out of these three tumours. There have been no published cases of the
management of MEN 1 in pregnancy. We report the first case of a 31-year-old
primigravida with a confirmed diagnosis of MEN 1 prior to conception. Due to the
rare nature of MEN 1, there are no guidelines on how such women should be
managed. The main issues were to assess and manage potential complications, such
as hypercalcaemia, diabetes mellitus and the symptoms from a pituitary tumour as
well the issues around a gastrinoma and monitor fetal well-being. A Caesarean
section was performed at 35 weeks gestation for a growth-restricted fetus with
raised umbilical artery Dopplers. The neonate was treated with intravenous
calcium secondary to hypocalcaemia. The patient and neonate recovered well. We
have demonstrated successful management of a woman with MEN 1 who completed her
pregnancy with few complications and a healthy neonate. It is vital for such
women to be managed in the context of a multidisciplinary team setting to
optimise maternal and fetal outcomes.
PMID- 27512438
TI - Successful pregnancy outcome in a woman with Turner's syndrome.
AB - Women with Turner's syndrome have a high incidence of cardiovascular
complications, endocrine and hypertensive disorders. Those with the 45X
chromosome complement require oocyte donation and in vitro fertilisation to
conceive. Pregnancies in such women are challenging to manage due to the high
risk of pregnancy-related hypertensive disorders, impaired glucose tolerance,
fetal growth restriction and preterm birth. Women also need to be aware of the
significant risk of aortic dilatation, dissection or rupture in pregnancy, which
may be fatal. Despite these risks, favourable obstetric outcomes are achievable
with careful pre-pregnancy counselling and cardiovascular assessment, intensive
multidisciplinary antenatal monitoring and individualised delivery planning. We
report the case of a 33-year-old woman with Turner's syndrome, pre-existing
hypertension, insulin-dependent diabetes and primary hypoparathyroidism who had a
successful pregnancy with good maternal and fetal outcomes despite the complexity
of her medical conditions.
PMID- 27512439
TI - First reported case of ganglioneuroblastoma in pregnancy and a review of the
literature.
AB - Ganglioneuroblastoma is a variant of neuroblastoma tumours with mature ganglion
cell differentiation which occurs commonly in cervical, mediastinal and
retroperitoneal locations. Approximately 90% of ganglioneuroblastomas are seen in
children younger than five years old. There are 50 adult cases of
ganglioneuroblastomas reported to date. Our patient is the 51st case and she is
the first to be diagnosed in pregnancy. Our patient's tumour site was the thoraco
abdominal retroperitoneal space adjacent to her kidney. This tumour is generally
diagnosed incidentally or by compression presentations, i.e. pain or neurological
symptoms. Our patient's ultrasound scan appearances triggered suspicion of an
atypical mass after presenting with loin pain. Caesarean section with tumour
removal in the same session is preferred if tumour is small and localized.
However in this case, there was uncertainty regarding the extent of the tumour.
Therefore, the patient underwent thoracotomy after delivery to excise the thoraco
abdominal tumour, which extended from the level of the T9 to L2 vertebrae.
PMID- 27512440
TI - The investigation and management of broad complex tachycardia and ventricular
standstill presenting in pregnancy: A case report.
AB - A 23 year old pregnant lady at 35 weeks gestation presented to accident and
emergency with worsening dyspnoea, palpitations and dizziness. Twelve lead
electrocardiogram, routine bloods and echocardiography were normal. Ambulatory
monitoring previously had shown an episode of monomorphic broad complex
tachycardia (BCT) and a short episode of ventricular standstill. She was admitted
for cardiac monitoring until delivery. Several episodes of ventricular standstill
and self-terminating BCT were recorded, which were not associated with symptoms.
The patient's symptoms either corresponded with sinus rhythm or supraventricular
tachycardia. She underwent elective caesarean section at 37 weeks with no
complications. The patient's symptoms reduced considerably post delivery, and she
was discharged three days later. Unfortunately she then had a presyncopal episode
whilst holding her baby. Due to concern regarding the safety of her baby she had
a permanent pacemaker implanted to allow safe beta-blockade. She remains
asymptomatic six months later.
PMID- 27512441
TI - Defining competencies for training in obstetric medicine.
PMID- 27512442
TI - Congenital cytomegalovirus infection: Clinical presentation, epidemiology,
diagnosis and prevention.
AB - Cytomegalovirus is the most common congenital infection causing serious disease
in infants. It is the leading infectious cause of sensorineural hearing loss and
neurodevelopmental disability in developed countries. Despite the clinical
importance of congenital cytomegalovirus, surveys show there is limited awareness
and knowledge in the medical and general community about congenital
cytomegalovirus infection. This article reviews the clinical features, global
epidemiology, transmission and risk factors for cytomegalovirus infections. It
also highlights several major advances made in recent years in the diagnosis and
prevention of cytomegalovirus infection during pregnancy. Although research is
ongoing, no therapy is currently proven to prevent or treat maternal, fetal or
neonatal cytomegalovirus infection. Education of women regarding hygiene measures
can help prevent cytomegalovirus infection and are currently the best strategy to
prevent congenital cytomegalovirus disease.
PMID- 27512444
TI - A longitudinal study of skin barrier function in pregnancy and the postnatal
period.
AB - BACKGROUND: It is unknown whether skin's barrier function changes in pregnancy.
Trans Epidermal Water Loss (TEWL) refers to the total amount of water loss
through the skin and TEWL can be measured non-invasively as an index of skin
barrier function. We measured TEWL during and after pregnancy to evaluate
pregnancy-related skin barrier function. METHODS: This was a prospective,
longitudinal cohort study of 52 low-risk, first-time pregnant women nested within
the Screening for Pregnancy Endpoints (SCOPE) Ireland study. TEWL (gwater/m2/h)
was measured three times during pregnancy: 19-21 weeks, 27-32 weeks and 36 weeks;
and three times postnatally: 2-4 days, 2 months and 6 months post-delivery. Data
were analysed using SPSS 18.0 and P > 0.05 was considered statistically
significant. RESULTS: A rise in TEWL was seen between each visit with the highest
readings, exceeding the normal range of 0-20 gwater/m(2)/h, recorded at two
months post-delivery. Forty women attended at two months post-delivery of whom 22
women had an average reading between 0 and 20 gwater/m(2)/h; 10 women had an
average reading between 21 and 40 gwater/m(2)/h and 8 women had an average
reading between 41 and 75 gwater/m(2)/h. Readings had returned to an average of 0
20 gwater/m(2)/h at six months postnatally. CONCLUSION: TEWL increases slightly
in pregnancy and the postnatal period. The clinical significance of this is
unclear and requires further investigation.
PMID- 27512443
TI - Pregnancy and cystic fibrosis: Approach to contemporary management.
AB - Over the previous 50 years survival of patients with cystic fibrosis has
progressively increased. As a result of improvements in health care, increasing
numbers of patients with cystic fibrosis are now considering starting families of
their own. For the health care professionals who look after these patients, the
assessment of the potential risks, and the process of guiding prospective parents
through pregnancy and beyond can be both challenging and rewarding. To facilitate
appropriate discussions about pregnancy, health care workers must have a detailed
understanding of the various important issues that will ultimately need to be
considered for any patient with cystic fibrosis considering parenthood. This
review will address these issues. In particular, it will outline pregnancy
outcomes for mothers with cystic fibrosis, issues that need to be taken into
account when planning a pregnancy and the management of pregnancy for mothers
with cystic fibrosis or mothers who have undergone organ transplantation as a
result of cystic fibrosis.
PMID- 27512445
TI - Trends in maternal deaths from epilepsy in the United Kingdom: a 30-year
retrospective review.
AB - OBJECTIVE: Neurological diseases remain the second most common cause of maternal
mortality from indirect causes, according to the last United Kingdom confidential
enquiry into maternal death. The maternal mortality rate from epilepsy is
reported as 0.61 per 100,000 maternities. The aim of this study was to analyse
the trends and causes of maternal death from epilepsy in the UK over the last 30
years. Information on sub-standard care associated with fatalities was also
consolidated to inform guidance and clinical care by obstetricians and physicians
caring for pregnant women with epilepsy. STUDY DESIGN: A retrospective review of
10 triennial confidential enquiry into maternal death reports (1979-2008) was
performed, encompassing 21,514,457 maternities. Late and coincidental deaths were
not included in the analyses. RESULTS: Between 1979 and 2008, there were 92
maternal deaths from epilepsy. The proportion of total maternal deaths from
epilepsy over 30 years is 3.7% (95% CI 3.0-4.5), which showed an increasing
trend. Sudden unexpected death in epilepsy remains the single greatest cause of
maternal death from epilepsy followed by aspiration of gastric contents during
seizures and drowning during bathing. CONCLUSION: All women with epilepsy should
be looked after by specialist combined obstetric and medical or neurological
teams in pregnancy to improve maternal and fetal outcomes.
PMID- 27512446
TI - Missed opportunities: Peripartum hepatic failure in a Chinese immigrant.
AB - Hepatitis B surface antigen (HBsAg) positivity presents unique management
challenges in pregnancy. We present the case of a 26-year-old HBsAg-positive
woman who presented at 35 weeks gestational age with nausea, vomiting, and
abdominal pain with markedly elevated liver enzymes. An elevated alpha feto
protein on antenatal screening had been misconstrued as fetal in origin. Magnetic
resonance imaging and liver biopsy confirmed hepatocellular carcinoma. She died
of fulminant hepatic failure two weeks after emergent delivery. This case
highlights the importance of adequate evaluation and management of pregnant
patients testing positive for HBsAg on routine antenatal testing.
PMID- 27512447
TI - Pregnancy in women after coronary revascularization.
AB - Pregnancy after coronary revascularization presents unique challenges to the
management of antiplatelet therapy, anesthesia and mode of delivery. We present
two cases where women of reproductive age required coronary revascularization
with drug eluting stents after a myocardial infarction, and discuss key aspects
of pregnancy and labor management.
PMID- 27512448
TI - Managing severe peripartum hyponatraemia: A case report.
AB - We present a case of severe peripartum hyponatraemia that occurred following a
major obstetric haemorrhage causing both an ischaemic stroke and Sheehan's
syndrome and outline the investigations and management strategy required.
PMID- 27512449
TI - A case of euglyacemic diabetic ketoacidosis in a patient with gestational
diabetes mellitus.
AB - A 30-year old woman at 30 weeks gestation with insulin-controlled gestational
diabetes was admitted with nausea and vomiting. Plasma glucose was 3.3 mmol/l
with pH 7.23 and raised capillary ketones at 6.1 mmol/l. She was diagnosed with
euglycaemic diabetic ketoacidosis. Cardiotocography showed good fetal movement
and accelerations. She was given intramuscular betamethasone and started on
intravenous dextrose, insulin and 0.9% saline with potassium chloride with
resolution of ketosis. Euglycaemic diabetic ketoacidosis has been reported during
pregnancy in patients with type 1 and type 2 diabetes. We believe that this is a
report of such an occurrence in a patient with gestational diabetes.
PMID- 27512450
TI - Acidosis: A potential explanation for adverse fetal outcome in intrahepatic
cholestasis of pregnancy. A case report.
AB - BACKGROUND: Intrahepatic cholestasis of pregnancy is a cholestatic disorder with
an increased risk for adverse perinatal outcome. The mechanism underlying
intrauterine demise is poorly understood. CASE: A nulliparous woman with
gestational age of 36 plus 6 weeks presented with suspected intrahepatic
cholestasis. Continuous CTG monitoring evolved from a normal pattern towards a
non-reassuring pattern. A male neonate was delivered by caesarean section. Apgar
scores 0, 1 and 4 at 1, 5 and 10 min. Fetal cord gas analysis showed pH 6.98,
base deficit -15 mmol/L. Blood results showed maternal serum bile acid
concentration of 220 umol/L. CONCLUSION: Our case suggests gradual evolution
towards hypoxia and acidosis. It is unknown whether certain components in the
bile acid concentrations might contribute to a fetal metabolic component of the
acidosis.
PMID- 27512451
TI - The UK maternal death report.
PMID- 27512452
TI - Prevention of mother-to-child transmission in South Africa: an ever-changing
landscape.
AB - Almost 30% of pregnant women attending public health clinics in South Africa are
HIV positive; which represents approximately 280,000 women each year. South
Africa has the largest antiretroviral therapy programme in the world, with over
2.7 million people on treatment in 2013. Since its belated and controversial
beginning, the Prevention of Mother-to-Child Transmission programme has achieved
a substantial reduction in vertical transmission. South Africa is justifiably
proud of this success. However, the history of Prevention of Mother-to-Child
Transmission (PMTCT) and antiretroviral therapy programmes in South Africa has
been fraught with delays and political intervention. South Africa could have
started both PMTCT and antiretroviral therapy programmes in 2000. Instead, the
AIDS denialist views of the government allowed the HIV epidemic to spiral out of
control. Roll-out of a national PMTCT programme began in 2002, but only after the
government was forced to do so by a Constitutional Court ruling. Now, a decade
later, HIV treatment and prevention programmes have been completely transformed.
This article will discuss the evolution of the HIV epidemic in South Africa, and
give a historical overview of the struggle to establish a national PMTCT, and the
impact of delaying PMTCT and treatment programmes on infant and maternal health.
PMID- 27512453
TI - Care of the HIV-infected pregnant woman in the developed world.
AB - The reduction of human immunodeficiency virus (HIV) transmission from mother to
child is one of the success stories of modern medicine and public health. In the
developed world, with universal HIV counseling and testing, antiretroviral
prophylaxis, scheduled Caesarean delivery if indicated, and avoidance of
breastfeeding, HIV transmission from mother to infant can be <2%. Despite this,
transmissions continue to occur, often due to lack of knowledge of HIV status.
Missed opportunities for prevention and prevention challenges include late
prenatal care, lack of HIV testing in pregnancy, lack of preconception
counseling, unintended pregnancy, and substance abuse. We review preconception
counseling including options for serodiscordant couples, and antepartum,
peripartum and postpartum care of the HIV-infected woman in the developed world,
and advocate for a comprehensive, collaborative, multidisciplinary approach.
PMID- 27512454
TI - Pregnancy in women with congenital heart disease.
AB - Due to advances in paediatric congenital heart surgery, there are a growing
number of women with congenital heart disease (CHD) reaching childbearing age.
Pregnancy, however, is associated with haemodynamic stresses which can result in
cardiac decompensation in women with CHD. Many women with CHD are aware of their
cardiac condition prior to pregnancy, and preconception counselling is an
important aspect of their care. Preconception counselling allows women to make
informed pregnancy decisions, provides an opportunity for modifications of
teratogenic medications and, when necessary, repair of cardiac lesions prior to
pregnancy. Less commonly, the haemodynamic changes of pregnancy unmask a
previously unrecognised heart lesion. In general, pregnancy outcomes are
favourable for women with CHD, but there are some cardiac lesions that carry high
risk for both the mother and the baby, and this group of women require care by an
experienced multidisciplinary team. This review discusses preconception
counselling including contraception, an approach to risk stratification and
management recommendations in women with some common CHDs.
PMID- 27512455
TI - Letter regarding: Managing severe peripartum hyponatraemia: A case report,
Obstetric Medicine: The Medicine of Pregnancy.
PMID- 27512456
TI - Authors' response to letter by Adam Morton regarding: "Managing severe peripartum
hyponatraemia: A case report".
PMID- 27512457
TI - Clinical practice guidelines in obstetric medicine.
PMID- 27512458
TI - Pregnancy in women with inherited metabolic disease.
AB - An increasing number of women with rare inherited disorders of metabolism are
becoming pregnant. Whilst, in general, outcomes for women and their children are
good, there are issues that need to be considered. Due to the rarity of many
conditions, there is limited specific guidance available on best management.
Prepregnancy counselling with information on inheritance, options for
reproduction, teratogenicity risk, potential impact on maternal health and long
term health of children should be offered. With appropriate specialist
management, the teratogenic risk of conditions such as maternal phenylketonuria
(PKU) can be eliminated, and the risk of metabolic decompensation in other
disorders of intoxication or energy metabolism significantly reduced. Newer
therapies, such as enzyme replacement therapy, appear to be safe in pregnancy,
but specific advice should be sought. Multidisciplinary management, and close
liaison between obstetricians and other specialists is required for women in whom
there is cardiac, renal, respiratory, joint or other organ involvement.
PMID- 27512459
TI - Prevention of gestational diabetes in pregnant women with risk factors for
gestational diabetes: a systematic review and meta-analysis of randomised trials.
AB - BACKGROUND: Gestational diabetes mellitus can be defined as 'glucose intolerance
or hyperglycaemia with onset or first recognition during pregnancy.' OBJECTIVE:
The objective of our systematic review was to see if there was any intervention
that could be used for primary prevention of gestational diabetes mellitus in
women with risk factors for gestational diabetes mellitus. SEARCH STRATEGY: Major
databases were searched from 1966 to Aug 2012 without language restriction.
SELECTION CRITERIA: Randomised trials comparing intervention with standard care
in women with risk factors for gestational diabetes were included. Meta-analysis
was performed in accordance with Preferred Reporting Items for Systematic Reviews
and Meta-Analysis statement. The primary outcome assessed was the incidence of
gestational diabetes. DATA COLLECTION AND ANALYSIS: Data from included trials
were extracted independently by two authors and analysed using Rev-Man 5. MAIN
RESULTS: A total of 2422 women from 14 randomised trials were included; which
compared diet (four randomised trials), exercise (three randomised trials),
lifestyle changes (five randomised trials) and metformin (two randomised trials)
with standard care in women with risk factors for gestational diabetes mellitus.
Dietary intervention was associated with a statistically significantly lower
incidence of gestational diabetes (Odds ratio 0.33, 95% CI 0.14 to 0.76) and
gestational hypertension (Odds ratio 0.28, 95% CI 0.09, 0.86) compared to
standard care. There was no statistically significant difference in the incidence
of gestational diabetes mellitus or in the secondary outcomes with exercise,
lifestyle changes or metformin use compared to standard care. CONCLUSIONS: The
use of dietary intervention has shown a statistically significantly lower
incidence of gestational diabetes mellitus and gestational hypertension compared
to standard care in women with risk factors for gestational diabetes mellitus.
PMID- 27512460
TI - Maternal mortality and its relationship to emergency obstetric care (EmOC) in a
tertiary care hospital in South India.
AB - OBJECTIVE: To determine the trends in maternal mortality ratio over 5 years at
JIPMER Hospital and to find out the proportion of maternal deaths in relation to
emergency admissions. METHODS: A retrospective analysis of maternal deaths from
2008 to 2012 with respect to type of admission, referral and ICU care and cause
of death according to WHO classification of maternal deaths. RESULTS: Of the 104
maternal deaths 90% were emergency admissions and 59% of them were referrals.
Thirty two percent of them died within 24 hours of admission. Forty four percent
could be admitted to ICU and few patients could not get ICU bed. The trend in
cause of death was increasing proportion of indirect causes from 2008 to 2012.
CONCLUSION: The trend in MMR was increasing proportion of indirect deaths. Ninety
percent of maternal deaths were emergency admissions with complications requiring
ICU care. Hence comprehensive EmOC facilities should incorporate Obstetric ICU
care.
PMID- 27512461
TI - Chronic kidney disease in pregnancy: Maternal and fetal outcomes and progression
of kidney disease.
AB - BACKGROUND: There is a paucity of Australian data regarding renal disease in
pregnancy. We undertook a retrospective cohort study at a tertiary institution to
examine the impact of renal disease on pregnancy outcomes and the effect of
pregnancy on disease progression. METHODS: A total of 55 pregnancies of patients
with renal disease admitted from 2003 to 2010 to the Royal Brisbane and Women's
Hospital were analysed. Pre-conception variables, fetal/delivery and maternal
outcomes were analysed in this group and in a control group of women with normal
kidney function pre-pregnancy. RESULTS: Of the 55 pregnancies, 71% experienced
pre-term delivery, 38% had intra-uterine growth restriction and 62% required
caesarean section. Of all, 60% of neonates required neonatal intensive care unit
(NICU) admission and six perinatal deaths occurred. Of all, 67% of women suffered
preeclampsia, 47% anaemia and 3 patients required dialysis in pregnancy.
Postpartum deterioration of renal function occurred in patients with pre
conception chronic kidney disease stage 3-5. CONCLUSIONS: Chronic kidney disease
of all stages is a risk factor for adverse pregnancy outcomes. In a tertiary
institution however, there is a high rate of successful pregnancy (84%).
PMID- 27512462
TI - Pregnancy outcomes in cystic fibrosis: a 10-year experience from a UK centre.
AB - BACKGROUND: Cystic fibrosis manifests as a multisystem disease, despite this
female fertility is relatively preserved with levels approaching that of the non
cystic fibrosis population. We reviewed pregnancies in cystic fibrosis patients
over a 10-year period from a UK adult cystic fibrosis centre by considering
maternal and fetal outcomes. METHODS: We conducted a retrospective case-note
review of pregnancies during 2003-2013 using respiratory and obstetric records.
RESULTS: We observed moderate falls in lung function immediately after delivery,
which persisted at 12 months postpartum. We found that a decline in lung function
at delivery was a marker for further decline in function during the subsequent
postpartum period. We found baseline lung function was predictive of gestational
age at delivery. We observed a high incidence of haemoptysis. CONCLUSION:
Consistent with current guidance we found pregnancy is feasible and well
tolerated in the majority of patients with cystic fibrosis. There was a high
incidence of haemoptysis, which warrants further study.
PMID- 27512463
TI - Infective endocarditis in pregnancy: Case report and review of the literature.
AB - Infective endocarditis in pregnancy is associated with high maternal and fetal
morbidity and mortality and is estimated to complicate approximately 1 in 100,000
pregnancies. We report the case of a 33-year-old patient who presented at 30
weeks and 3 days gestation in her third pregnancy. The patient described a 3 week
history of feeling generally unwell, an episode of temporary speech disturbance,
right shoulder tip pain, left subscapular pain on inspiration and chest
discomfort. Investigations included an echocardiogram, which revealed a large
mobile mass on the aortic coronary cusp and a small mass on the non-coronary
cusp. There was significant aortic regurgitation. Blood cultures were positive
for staphylococcus lugdunensis. A diagnosis of infective endocarditis was made.
The patient deteriorated, with worsening cardiac function, and proceeded to have
a caesarean section on day 7 of admission. Her baby had multiple limb
abnormalities, subsequently diagnosed as arthrogryposis multiplex congenita.
Aortic valve replacement with a mechanical valve was then performed on day 3 post
partum. The patient recovered well post operatively and was discharged home with
her baby on day 45 post partum. The commonest complications of IE are congestive
cardiac failure, perivalvular extension and systemic embolization. The management
of infective endocarditis in pregnancy is similar to that of the non-pregnant
however there is high foetal mortality associated with cardiopulmonary by-pass
for cardiac surgery. The patient described here developed staphylococcus
lugdunensis infective endocarditis, which is a rare but aggressive causative
organism in infective endocarditis. Infective endocarditis in pregnancy is a rare
but serious condition with significant fetal and maternal morbidity and
mortality. Early diagnosis with a multidisciplinary team approach is essential to
improve outcomes.
PMID- 27512464
TI - Putting the world to rights.
PMID- 27512465
TI - Monogenic diabetes and pregnancy.
AB - Monogenic diabetes is frequently mistakenly diagnosed as either type 1 or type 2
diabetes, yet accounts for approximately 1-2% of diabetes. Identifying monogenic
forms of diabetes has practical implications for specific therapy, screening of
family members and genetic counselling. The most common forms of monogenic
diabetes are due to glucokinase (GCK), hepatocyte nuclear factor (HNF)-1A and HNF
4A, HNF-1B, m.3243A>G gene defects. Practical aspects of their recognition,
diagnosis and management are outlined, particularly as they relate to pregnancy.
This knowledge is important for all physicians managing diabetes in pregnancy,
given this is a time when previously unrecognised monogenic diabetes may be
uncovered with careful attention to atypical features of diabetes misclassified
as type 1, type 2, or gestational diabetes.
PMID- 27512466
TI - Restless leg syndrome in pregnancy.
AB - Restless leg syndrome, more recently renamed Willis-Ekbom disease, is a condition
that disrupts sleep and occurs more frequently in the pregnant population. We
present a 39-year-old woman with restless legs syndrome in the third trimester
and discuss the epidemiology, pathophysiology and therapeutic options in the
pregnant population while highlighting the challenges posed by the lack of safety
data of approved drugs.
PMID- 27512467
TI - Acute respiratory failure in pregnancy.
AB - Respiratory failure affects up to 0.2% of pregnancies, more commonly in the
postpartum period. Altered maternal respiratory physiology affects the assessment
and management of these patients. Respiratory failure may result from pregnancy
specific conditions such as preeclampsia, amniotic fluid embolism or peripartum
cardiomyopathy. Pregnancy may increase the risk or severity of other conditions,
including thromboembolism, asthma, viral pneumonitis, and gastric acid
aspiration. Management during pregnancy is similar to the nonpregnant patient.
Endotracheal intubation in pregnancy carries an increased risk, due to airway
edema and rapid oxygen desaturation following apnea. Few data are available to
direct prolonged mechanical ventilation in pregnancy. Chest wall compliance is
reduced, perhaps permitting slightly higher airway pressures. Optimizing
oxygenation is important, but data on the use of permissive hypercapnia are
limited. Delivery of the fetus does not always improve maternal respiratory
function, but should be considered if benefit to the fetus is anticipated.
PMID- 27512468
TI - Gestational weight gain and medical outcomes of pregnancy.
AB - This narrative review discusses gestational weight gain (GWG) and medical
outcomes of pregnancy, including metabolic, cardiovascular, respiratory,
musculoskeletal and psychiatric systems. Taken as a whole, the available evidence
shows that excessive GWG increases the risk of all medical complications of
pregnancy, and negatively impacts the long-term health and weight of both mothers
and their offspring. Briefly, interventions to encourage appropriate GWG are
discussed and readers are directed to resources to facilitate discussion of
pregnancy weight.
PMID- 27512469
TI - Global obstetric medicine: Collaborating towards global progress in maternal
health.
AB - Globally, the nature of maternal mortality and morbidity is shifting from direct
obstetric causes to an increasing proportion of indirect causes due to chronic
conditions and ageing of the maternal population. Obstetric medicine can address
an important gap in the care of women by broadening its scope to include
colleagues, communities and countries that do not yet have established obstetric
medicine training, education and resources. We present the concept of global
obstetric medicine by highlighting three low- and middle-income country
experiences as well as an example of successful collaboration. The article also
discusses ideas and initiatives to build future partnerships within the global
obstetric medicine community.
PMID- 27512470
TI - Acute pancreatitis with eclampsia-preeclampsia syndrome and poor maternal
outcome: two case reports and review of literature.
AB - Acute pancreatitis in pregnancy is a rare entity and has been reported to be
associated with preeclampsia in the literature. Fulminant pancreatitis may have a
guarded prognosis despite intensive multidisciplinary management. Two cases of
maternal mortality in women with acute pancreatitis noted in the setting of
preeclampsia-eclampsia syndrome are reported here.
PMID- 27512471
TI - All that wheezes is not asthma: A cautionary case study of shortness of breath in
pregnancy.
AB - BACKGROUND: Shortness of breath is a common physiological pregnancy presentation,
secondary to both hormonal and mechanical effects. Its pathological causes are
common (asthma exacerbation or infection); new-onset cardiac pathology is rarely
considered. CASE: JC, a 39-year old G4P2T1, presented at 34 weeks' gestation with
shortness of breath unrelieved by salbutamol. History included asthma, poly-drug
abuse and smoking. Initial presentation was consistent with asthma exacerbation
and she was treated as such. There was deterioration of symptoms and on re
examination raised jugular venous pressure was noted with bibasal lung
crepitations and cardiac systolic murmur. Echocardiogram showed severe
cardiomyopathy (left ventricular ejection fraction 20%). JC was commenced on
diuretics, digoxin and fluid restricted. Labour was induced at 35 weeks'
gestation, with birth of a healthy female infant (BW 2475 g) by elective assisted
vaginal delivery. Cardiac function improved in subsequent weeks, confirming
peripartum cardiomyopathy. CONCLUSION: Peripartum cardiomyopathy affects 1 in
2500-4000 live births. Over 90% of women regain normal cardiac function
postpartum with optimal medical management. Peripartum cardiomyopathy presents a
diagnostic conundrum as its primary symptoms mimic not only those of normal
pregnancy but also a number of other, more common conditions. It is important to
consider cardiac causes of shortness of breath initially, and vital to revisit an
initial non-cardiac shortness of breath diagnosis if there is no sustained
improvement with treatment. In this case, asthma history and initial wheeze on
examination impeded correct diagnosis; however, the situation was re-evaluated
and correct diagnosis made when the patient's shortness of breath deteriorated.
Subsequent multidisciplinary management and birth in an appropriate setting
facilitated the best outcome for both mother and baby.
PMID- 27512472
TI - Coronary artery disease secondary to familial hypercholesterolaemia: An
infrequent cause of increasingly common pregnancy co-morbidity.
AB - BACKGROUND: Cardiovascular disease affects 0.2-4% of pregnancies. Coupled with
the physiological stress of pregnancy, cardiovascular disease may present
significant management challenges including appropriate risk:benefit analysis of
medical and surgical management options. CASE: A 33-year-old gravida 4 para 1
miscarriage 2 presented at 18 weeks' gestation to the high-risk pregnancy service
with a history of coronary artery disease and homozygous familial
hypercholesterolaemia. Pre-pregnancy echocardiogram showed probable aortic
xanthoma and preserved cardiac function. Prior to planned interventional
cardiology assessment for her coronary artery disease she became pregnant, taking
aspirin and multivitamins only. She had exertional angina responsive to
metoprolol, agreed to recommencing statin therapy when serum cholesterol
worsened, but declined angiography during pregnancy. At 36 weeks' gestation, she
had further angina symptoms but no acute coronary syndrome. Induction in the High
Dependency Unit with elective assisted vaginal delivery of a healthy female
infant (birthweight 2460 g) occurred at 37 weeks. She underwent triple-vessel
coronary artery bypass postpartum, recovering well. CONCLUSION: Whilst this
specific condition is rare, the increase in cardiovascular disease and
cardiovascular risks in the obstetric population emphasises the need for clear,
multidisciplinary management from the outset of pregnancy for these women.
PMID- 27512473
TI - Editorial.
PMID- 27512474
TI - Severe gestational hypertriglyceridemia: A practical approach for clinicians.
AB - Severe gestational hypertriglyceridemia is a potentially life threatening and
complex condition to manage, requiring attention to a delicate balance between
maternal and fetal needs. During pregnancy, significant alterations to lipid
homeostasis occur to ensure transfer of nutrients to the fetus. In women with an
underlying genetic predisposition or a secondary exacerbating factor, severe
gestational hypertriglyceridemia can arise, leading to devastating complications,
including acute pancreatitis. Multidisciplinary care, implementation of a low-fat
diet with nutritional support, and institution of a hierarchical therapeutic
approach are all crucial to reduce maternal and fetal morbidity. To avoid
maternal pancreatitis, close surveillance of triglycerides throughout pregnancy
with elective hospitalization for refractory cases is recommended. Careful
dietary planning is required to prevent neural and retinal complications from
fetal essential fatty acid deficiency. Questions remain about the safety of
fibrates and plasmapheresis in pregnancy as well as the optimal timing for
induction and delivery of these women.
PMID- 27512475
TI - Insomnia and sleep deficiency in pregnancy.
AB - Insomnia and sleep deficiency in pregnancy are very common with most women
reporting sleep disturbances during pregnancy. Insomnia and sleep deficiency are
also more prevalent as pregnancy progresses, possibly related to pregnancy
related physical symptoms or discomfort. There is increasing evidence indicating
that these sleep problems may be associated with adverse maternal and fetal
outcomes such as depressive symptoms, increased pain during labor, more Caesarean
sections, preterm birth, and low birth weight. Treatment of insomnia remains
challenging as some of the more commonly used sleep inducing medications such as
benzodiazepines and hypnotic benzodiazepine receptor agonists may be associated
with adverse neonatal outcomes. Nonpharmacological treatments such as cognitive
behavioral therapy are available but the data in pregnancy is often lacking.
PMID- 27512476
TI - Antenatal steroids for fetal lung maturity: Time to target more frequent doses to
fewer women?
AB - Antenatal corticosteroids for fetal lung maturation have become mainstay
treatment in women thought to be at high-risk of premature birth. To ensure
treatment efficacy before delivery, the current practice is to administer
steroids early to a woman considered at risk; however, neonatal benefit is lost
after the seven-day treatment-to-delivery window. Over half of women who deliver
before 34 weeks' gestation do not receive antenatal corticosteroids within this
timeframe, but many still deliver prematurely; however, clinicians are reluctant
to administer repeated courses of steroids due to concerns, among others, of
impaired fetal growth. However, evidence is mounting regarding the optimal timing
for steroids, including substantive benefits close to delivery, and the benefits
of repeated courses if delivery has not occurred. Better targeted treatment is
required to allow for maximum benefit; reducing unnecessary treatment in low-risk
women, while targeting therapy in the high-risk cohort and offering repeat
courses if the seven-day window is exceeded. Novel tools to aid prediction may
help implement this strategy.
PMID- 27512477
TI - Pituitary apoplexy in pregnancy: A case series and literature review.
AB - BACKGROUND: Severe headache during pregnancy is a challenging condition that may
rarely imply endocrine disturbances. Rapid recognition of pituitary apoplexy is
needed to improve pregnancy outcome. OBJECTIVE: To review and compare maternal
and fetal outcomes after pituitary apoplexy. METHODS: Four cases of pituitary
apoplexy during pregnancy in our centre are reported and literature review
covering the past 54 years was performed. RESULTS: In the four cases presented
and the 33 reported in the literature, most women presented with severe headaches
and systemic symptoms. Overall, 42% were treated surgically, 31% received
bromocriptine or cabergoline and 61% were given hormone replacement. No major
obstetrical complication was reported and all babies were healthy. CONCLUSION:
Pituitary apoplexy is a rare cause of sudden and severe headache during
pregnancy. Rapid identification of this condition with potentially associated
endocrine disturbances is important to ensure maternal and fetal well-being. A
multidisciplinary team approach seems to reduce morbidity and mortality.
PMID- 27512479
TI - Drug-induced fulminant hepatic failure in pregnancy.
AB - Liver disease in pregnancy can be classified as predating, co-incidental or
unique to pregnancy. Medications are often overlooked as a significant cause of
liver disease. We present the case of a 39-year-old patient who presented at 20
weeks with jaundice, elevated liver enzymes, and abnormal liver function
progressing eventually to fulminant hepatic failure. The patient was on
methyldopa and labetalol from 12 weeks' gestational age. Liver biopsy was
consistent with drug-induced liver injury. Both methyldopa and labetalol have
been associated with hepatotoxicity including liver failure. This case highlights
the importance of including medications as a cause of liver failure in pregnant
patients.
PMID- 27512478
TI - Antenatal haemoglobinopathy screening: Patterns within a large obstetric service.
Working towards a standard of care.
AB - BACKGROUND: Antenatal screening can predict clinically significant
haemoglobinopathies, however in Australia, practices are not standardised and are
evolving as the population becomes more ethnically diverse. This study describes
antenatal screening practices in a large Australian laboratory/antenatal service.
METHODS: Data were collected retrospectively on consecutive antenatal haemoglobin
electrophoresis over 16 months and correlated with obstetric data, obtained from
the local obstetric database. RESULTS: 462 patients were included, with an
average gestation of 25.8 weeks. 'Pregnancy' was the most common stated
indication, with absent indication/clinical information in 8%. Gestational age
was documented in 54%. In 15%, no contact details of the referrer were documented
and partner screening was traceable in only 25 cases (5.4%). In 82% of cases, no
abnormalities were detected. Beta thalassemia trait was the most common positive
result. Only 52% of patients had recent iron studies. The mean haemoglobin was
111.6 g/L and mean cell volume was 80.5 fl at the time of testing. Ethnicity was
documented on the request form in 3%. After Australasia, the most common
ethnicity of patients was South East Asia and the Middle East. CONCLUSION:
Referral patterns in our health service are diverse and reflect our changing
population and care practices. Detailed guidelines are required and we propose a
comprehensive algorithm for general use where selective screening is practiced
within an Australasian population or one with similar demographics.
PMID- 27512480
TI - Rare problems with RhD immunoglobulin for postnatal prophylaxis after large
fetomaternal haemorrhage.
AB - We report a case of unusually large fetomaternal haemorrhage in a RhD- patient;
of symptomatic non-sustained haemolysis of fetal red cells in the maternal
circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a
failure to prevent RhD alloimmunisation. The haemolytic reaction is not
previously reported in this patient group and we suggest would be limited to
patients where the number of fetal red cells in the circulation is high. We
advocate caution in treatment and spaced dosing of RhD immunoglobulin where the
required dose is high, and refer readers to the WinRhoSDFTM RhD immunoglobulin
product information for their updated dosing recommendations. There is a need for
better understanding of pathophysiology and RhD immunoglobulin effects, to
further reduce alloimmunisation rates, and we support the reporting of
prophylaxis failures to haemovigilance programmes as is in place in the United
Kingdom.
PMID- 27512481
TI - Percutaneous mitral commisurotomy during pregnancy - A report of two cases
performed in a United Kingdom tertiary centre and a review of the literature.
AB - We report two cases of severe mitral stenosis where percutaneous mitral
commisurotomy was performed within pregnancy. The first case involves an
emergency procedure for a new diagnosis of severe mitral stenosis in a woman
presenting with pulmonary oedema at 27 weeks' gestation. The second case is of a
woman known to have mitral stenosis who underwent a semi-elective procedure for
deterioration in symptoms. This procedure is not commonly performed in the United
Kingdom because of low incidence of rheumatic heart disease. In addition,
percutaneous mitral commisurotomy during pregnancy is rarely performed in the
United Kingdom because of the improved healthcare system where majority of the
women with moderate to severe mitral stenosis (even asymptomatic) will undergo
planned interventions (percutaneous mitral commisurotomy or mitral valve surgery)
before contemplating pregnancy. These cases highlight both the acute and chronic
presentations of mitral stenosis and the impact pregnancy has on this condition.
In addition, these cases show the importance of retaining skills in performing
percutaneous mitral commisurotomy within our United Kingdom cardiologists.
PMID- 27512482
TI - Presentation and management of acute hypertriglyceridemic pancreatitis in
pregnancy: A case report.
AB - Pancreatitis related to hypertriglyceridemia can occasionally occur during
pregnancy, particularly if there are underlying genetic abnormalities in lipid
metabolism. We report the case of a 27-year-old female with hypertriglyceridemic
pancreatitis in pregnancy that was treated initially with lipid lowering
medications, followed by plasma exchange for persistently elevated triglyceride
levels. Despite multiple interventions, she developed recurrent pancreatitis and
simultaneously had a preterm birth. In this case report, we highlight the various
therapies and the use of plasmapharesis in secondary prevention of
hypertriglyceridemic pancreatitis in pregnancy.
PMID- 27512483
TI - Prescribing in pregnancy.
PMID- 27512484
TI - Preconception counselling for women with acromegaly: More questions than answers.
AB - BACKGROUND AND AIMS: Approximately 174 pregnancies in acromegaly have been
reported. Our objectives were to identify the key challenges of preconception
counselling in this population. METHODS: Case series of three acromegalic women
with desire for pregnancy. Issues were identified from chart review and
discussion with attending physicians. Literature review of acromegaly and
pregnancy was conducted. RESULTS: Important issues identified included: impact of
acromegaly on fertility, management of acromegaly in the peripartum period,
screening for associated conditions, risk of progression of acromegaly/tumour
growth during pregnancy, impact of acromegaly on pregnancy outcomes, surveillance
during pregnancy, method of delivery and impact on neonatal outcomes and
breastfeeding. CONCLUSIONS: Pregnancy can be safely achieved in patients with
acromegaly. There is little evidence to guide recommendations around conception
and pregnancy surveillance. Patients can be reassured that in most situations,
pregnancy proceeds without complication and that medical treatment can be used
during pregnancy if necessary.
PMID- 27512485
TI - Thrombocytopenic syndromes in pregnancy.
AB - The physiological changes in pregnancy result in platelet counts that are lower
than in nonpregnant women. Consequently, thrombocytopenia is a common finding
occurring in 7-12% of pregnant women. Gestational thrombocytopenia, the most
common cause of low platelet counts, tends to be mild in most women and does not
affect maternal, fetal or neonatal outcomes. Gestational thrombocytopenia needs
to be distinguished from other less common causes of isolated thrombocytopenia,
such as immune thrombocytopenia, which affects approximately 3% of
thrombocytopenic pregnant women and can lead to neonatal thrombocytopenia.
Hypertensive disorders of pregnancy and thrombotic microangiopathies are both
associated with thrombocytopenia. They share a considerable number of similar
characteristics and are associated with significant maternal and neonatal
morbidity and rarely mortality. Accurate identification of the aetiology of
thrombocytopenia and appropriate management are integral to optimizing the
pregnancy, delivery and neonatal outcomes of this population. Clinical cases are
described to illustrate the various aetiologies of thrombocytopenia in pregnancy
and their treatment.
PMID- 27512486
TI - Frequency and type of medications and vaccines used during pregnancy.
AB - Providing safe pharmacotherapy for pregnant women is challenging. Nearly all
pregnant women are prescribed or inadvertently receive medication during their
pregnancy. We reviewed the scientific literature to identify the specific
medications and vaccines that are most often used during pregnancy and described
them by category and indication. Our interest was to update the research before
the implementation of the recently released FDA labeling rule for pregnancy and
lactation that eliminates the use of pregnancy categories in product labels. Our
results confirm that most products taken during pregnancy are over-the-counter or
in the former FDA pregnancy categories A or B. However, medications taken prior
to pregnancy recognition (inadvertent exposures) and those prescribed for chronic
illness such as allergies, depression, and pain are of concern. A better
understanding of medication and vaccine utilization during pregnancy may help
clinicians reduce inadvertent first trimester exposures and improve the safe and
effective treatment of pregnant women.
PMID- 27512487
TI - Ondansetron and pregnancy: Understanding the data.
AB - Nausea and vomiting of pregnancy (NVP) is a common condition affecting 75% of
pregnant women. NVP generally commences early in the first trimester, peaking in
severity between 7 and 12 weeks and in over 90% symptoms will have abated by week
20. Thus, the time when women are most likely to have NVP and require treatment
coincides with the embryonic period when there is maximum susceptibility to any
teratogenic risk. Following the thalidomide tragedy of 55 years ago there is a
particular awareness and sensitivity about these potential risks, especially in
relation to any medication used to treat NVP. Despite several studies showing no
clear benefits of ondansetron over other NVP treatments such as doxylamine, and
the paucity of safety data, the off-label prescribing and use of ondansetron to
treat NVP has increased significantly worldwide. Albeit based on limited human
pregnancy data, ondansetron has not been associated with a significantly
increased risk of birth defects or other adverse pregnancy outcomes. This review
attempts to highlight some of the difficulties in interpreting the available data
and the need to follow practical guidelines regarding treatment of NVP.
PMID- 27512488
TI - The influence of obesity on perinatal outcomes in pregnancies achieved with
assisted reproductive technology: A population-based retrospective cohort study.
AB - OBJECTIVE: To determine the influence of obesity on neonatal outcomes of
pregnancies resulting from assisted reproductive technology. METHODS: Population
based retrospective cohort study of all non-anomalous, live births in Ohio from
2007 to 2011, comparing differences in the frequency of adverse neonatal outcomes
of women who conceived with assisted reproductive technology versus spontaneously
conceived pregnancies and stratified by obesity status. Primary outcome was a
composite of neonatal morbidities defined as >=1 of the following: neonatal
death, Apgar score of <7 at 5 min, assisted ventilation, neonatal intensive care
unit admission, or transport to a tertiary care facility. RESULTS: Rates of
adverse neonatal outcomes were significantly higher for assisted reproductive
technology pregnancies than spontaneously conceived neonates; non-obese 25%
versus 8% and obese 27% versus 10%, p < 0.001. Assisted reproductive technology
was associated with a similar increased risk for adverse outcomes in both obese
(adjusted odds ratio (aOR): 1.33, 95% confidence interval (CI): 1.11-1.59) and
non-obese women (aOR: 1.34, 95% CI: 1.18-1.51) even after adjustment for
coexisting risk factors. This increased risk was driven by higher preterm births
in assisted reproductive technology pregnancies; obese (aOR: 1.06, 95% CI: 0.86
1.31) and non-obese (aOR: 1.15, 95% CI: 1.00-1.32). DISCUSSION: Assisted
reproductive technology is associated with a higher risk of adverse neonatal
outcomes. Obesity does not appear to adversely modify perinatal risks associated
with assisted reproductive technology.
PMID- 27512489
TI - Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): A warning.
AB - Direct oral anticoagulants (DOACs or NOACs -non-vitamin K oral anticoagulants),
as the name suggests, are oral anticoagulants with a direct inhibitory action
either against factor X or factor II (thrombin). Pregnant women were excluded
from participating in all the large trials of the DOACs and they are considered
contra-indicated in pregnancy and breast feeding. We present a case of
inadvertent exposure to rivaroxaban in a woman who presented at 25 weeks'
gestation. The management of her pregnancy and delivery is described, and the
previous published case reports are reviewed with a discussion about the use of
DOACs in woman of childbearing age.
PMID- 27512490
TI - Adrenal Cushing's syndrome in pregnancy: Clinical and molecular characterisation
of a case.
AB - BACKGROUND: Cushing's syndrome is rare during pregnancy and more commonly due to
adrenal pathology, in contrast to the non-pregnant population. Increased levels
of cortisol-binding globulin and placental production of corticotropin-releasing
hormone and adrenocorticotropic hormone complicate the diagnostic strategies
usually employed. CASE: A 32-year-old G1P0 at 15/40 gestation presented with
severe peripheral oedema and excessive weight gain. Examination revealed pitting
oedema to the abdominal wall, wide violaceous striae, moon facies and acne.
Cortisol excess was confirmed with elevated 24 h urinary free cortisol, raised
midnight salivary cortisol and lack of diurnal variation. Adrenocorticotropic
hormone ranged between 22 and 36 pg/ml (5-8 pmol/L). Fetal ultrasound confirmed a
single live intrauterine gestation with an incidental finding of a maternal left
adrenal mass. Magnetic resonance imaging confirmed an adrenal mass measuring 3.0
* 4.4 * 4.1 cm. She underwent a laparoscopic left adrenalectomy at 18 weeks'
gestation without complication. Her postoperative cortisol level was
undetectable. Hydrocortisone replacement was commenced with slow weaning as an
outpatient. Histology was consistent with an adrenal adenoma.
Immunohistochemistry revealed strong staining for the luteinising
hormone/choriogonadotropin receptor, and expression of the luteinising
hormone/choriogonadotropin receptor gene was in the range seen in normal ovary.
DNA analysis revealed a mutation in GNAS encoding the Galpha subunit in the
cyclic adenosine monophosphate pathway. CONCLUSION: Cushing's syndrome may
present in pregnancy as a result of betahCG acting on the luteinising
hormone/choriogonadotropin receptor over-expression by the adenoma amplifying the
aberrant cyclic adenosine monophosphate signaling implicated in the development
of cortisol-secreting adenomas.
PMID- 27512491
TI - Life-threatening ketoacidosis in a pregnant woman with psychotic disorder.
AB - Pregnancy is an insulin resistant state. Hyperglycaemia and gestational diabetes
mellitus are well-recognised complications even in women without existing
metabolic syndrome or obesity. Pregnant women also appear to be more vulnerable
to ketoacidosis, particularly after short periods of reduced oral intake in the
third trimester, and may present with very severe starvation ketoacidosis,
prompting emergent delivery. We present a case of a woman with a background of
depression and psychotic episodes. Olanzapine had been commenced after a
psychotic episode at 20 weeks' gestation. Gestational diabetes mellitus was
diagnosed at 28 weeks, and she was then admitted at 31 weeks with severe
euglycaemic ketoacidosis following a short period of vomiting. She underwent
caesarean section when the metabolic disturbances did not resolve with medical
treatment. We believe atypical antipsychotic therapy contributed to the profound
insulin resistance seen here, and that obstetricians, physicians and
psychiatrists must be aware of the risks conferred by these agents in pregnancy.
PMID- 27512492
TI - Ebola and pregnancy.
PMID- 27512493
TI - Zika infection: From obscurity to public health emergency.
PMID- 27512494
TI - Two case reports of generalized pustular psoriasis of pregnancy: Different
outcomes.
AB - Generalized pustular psoriasis of pregnancy is a rare dermatosis with potential
serious consequences for both the mother and fetus. Treatment is difficult and
historically steroids were the mainstay of treatment. Cyclosporin has been used
for a few cases resistant to steroids. We report our own experience of two cases
of generalized pustular psoriasis of pregnancy. Cases of generalized pustular
psoriasis of pregnancy need review by a dermatologist with experience of skin
disorders in pregnancy. Both the fetus and mother need to be monitored closely
when systemic illness occurs, as there is a risk of stillbirth. Maternal sepsis
is a known complication of generalized pustular psoriasis of pregnancy.
Cyclosporin, when used appropriately is effective and relatively safe.
PMID- 27512495
TI - Pregnancy and ketoacidosis: Is pancreatitis a missing link?
AB - Non-diabetic ketoacidosis is increasingly recognised in pregnancy, particularly
during the third trimester, and is usually associated with vomiting. In many
cases, the cause of the vomiting is not identified and resolves rapidly,
alongside the metabolic abnormalities, following delivery. Here, we report three
cases in which pancreatitis was identified as an underlying cause of the
gastrointestinal symptoms. To our knowledge, these are the first reports of
pancreatitis precipitating non-diabetic ketoacidosis in pregnancy. This case
series highlights the importance of searching for a precipitant for non-diabetic
ketoacidosis in pregnancy, rather than focusing solely on management of the
resulting metabolic abnormalities.
PMID- 27512496
TI - Update on inherited disorders of haemostasis and pregnancy.
AB - Inherited bleeding disorders have the potential to cause bleeding complications
during pregnancy, childbirth and the postpartum period as well as effect fetal
outcomes. There is an evolving understanding of the need for specialised and
individualised care for affected women during these times. The aim for each
patient is to estimate the risk to mother, fetus and neonate; to implement
measures to minimise these risks; and to anticipate complications and develop
contingencies for these scenarios. This includes accurate diagnosis,
preconceptual care, prenatal diagnostic options, antenatal care, delivery and
postpartum care as well as care of an affected neonate. An understanding of the
physiologic haemostatic changes associated with pregnancy as well as the scope of
defects, inheritance and management of inherited bleeding disorders is paramount
when caring for these women. Collaborative and prospective management in
conjunction with haematology services underpins the approach advocated. This
review draws on the available literature, and outlines the principles of care for
women with inherited bleeding disorders before, during and after pregnancy, as
well as their babies, based on both available data and collective clinical
experience.
PMID- 27512497
TI - Momentary stress, cortisol, and gestational length among pregnant victims of
childhood maltreatment: a pilot study.
AB - BACKGROUND: Pregnant victims of childhood maltreatment are more likely to deliver
preterm. The mechanisms explaining this relationship are unclear. The goal of the
current pilot study was to investigate whether momentary stress and cortisol
serve as mechanisms linking maltreatment history to gestational length. METHODS:
Seventeen women enrolled in the study (35% maltreated). Women completed two study
sessions at 27 and 34 weeks gestation. Following each session, at four times/day
over two days, women reported their momentary stress levels by text message and
provided corresponding salivary cortisol samples. Gestational length was
determined by medical chart review. RESULTS: Higher reports of momentary stress
were associated with shortened gestational length. High stress predicted lower
cortisol concentrations for women with maltreatment histories but higher
concentrations among women without maltreatment. CONCLUSION: Results from this
pilot study provide preliminary evidence for understanding mechanisms explaining
increased risk for preterm birth among childhood maltreatment victims.
PMID- 27512498
TI - Perinatal determinants of D-dimer levels in a cross-sectional study of low risk
pregnant women.
AB - BACKGROUND: To examine perinatal determinants of the antenatal levels of D
dimers. METHODS: Cross-sectional study of 760 low risk pregnant women recruited
into five gestational groups. Variables examined in antenatal groups included
maternal age, body mass index, parity, smoking, family history venous
thromboembolism (VTE) and previous use of the oral contraceptive pill (OCP).
Onset of labour and mode of delivery were also examined in the post-natal group.
RESULTS: D-dimer levels in group 4 (38-40 + 6) were significantly lower in the
women with a history of taking the OCP when compared to those that had not taken
it in the past (P = 0.027). In the day 2 post-natal group, the median level of D
dimer was significantly higher in primparous when compared to multiparous women
(P = 0.015). The median D-dimer levels were significantly lower in the elective
Caesarean section group in comparison to spontaneous onset (P = 0.003) and
induction of labour (P = 0.016). When the mode of delivery was examined, the
median D-dimer levels were significantly lower in those that had an elective
Caesarean section when compared to normal vaginal delivery (P = 0.008) and
instrumental vaginal delivery (P = 0.007). Women post elective Caesarean section
had a significantly lower D-dimer than those after emergency Caesarean section (P
= 0.008). DISCUSSION: There are some significant differences in D-dimer levels
when certain perinatal determinants are examined. This work is potentially
beneficial to the future diagnosis of VTE in pregnancy as it supports previously
published recommended D-dimer levels for the diagnosis of VTE in pregnancy.
PMID- 27512499
TI - Pregnancy outcomes of antiphospholipid syndrome: In a low resource South Asian
setting.
AB - PROBLEM: Antiphospholipid syndrome is associated with recurrent pregnancy loss,
and specific treatment improves pregnancy outcome. Laboratory diagnosis is
limited in South Asia. We assessed management outcomes of definite/probable
antiphospholipid syndrome treated at a tertiary centre in Sri Lanka. METHOD:
Descriptive cross-sectional study of pregnancy outcomes with heparin and aspirin
therapy. OUTCOME MEASURES: miscarriage, intrauterine death and live birth when
compared to previous untreated pregnancies. RESULTS: Of 646 gestations in 145
women, 146 (22.6%) received specific treatment. In the preceding pregnancies
without specific treatment, the rates of miscarriage, late fetal loss, stillbirth
and live birth were 60%, 26%, 8% and 7%, respectively. Following specific
treatment with low-dose aspirin +/- low-molecular weight heparin in 146
pregnancies (145 women), the rates of miscarriage, late fetal loss, stillbirth
and live birth were 14%, 10%, 3% and 74%, respectively. Mean birth weight was
2.54 +/- 0.62 kg, preterm births complicated 32 (29.6%) with a mean gestational
age at delivery 33.7 +/- 2.6 weeks, with three neonatal deaths. Maternal
complications were: pre-eclampsia 16 (10.9%), gestational diabetes 28 (19.2%),
antepartum haemorrhage in 1 patient. Only 73/145 (50.3%) women had laboratory
confirmation of antiphospholipid syndrome, while others were treated empirically.
Live births in diagnosed vs. empiric treatment - 80.8% vs. 67.1%. CONCLUSION:
Pregnant women with clinical antiphospholipid syndrome when treated with low-dose
aspirin and heparin, the live birth rate of 7% in the previous pregnancy resulted
in live births of 74% in a resource limited South Asian setting.
PMID- 27512500
TI - Adrenal infarction in a healthy pregnant woman.
AB - Adrenal infarction is a very rare event but occasionally seen in hypercoagulable
states. We present a case of a 31-year-old woman at 38 weeks of gestation who
developed a severe upper abdominal pain and unilateral adrenal infarction due to
thrombosis of the adrenal vein. The only thrombogenic factor found was pregnancy.
The case highlights that adrenal infarction may complicate a normal pregnancy and
should be included in the differential diagnosis of the acute abdomen in
pregnancy.
PMID- 27512501
TI - Management of venous thromboembolism secondary to ovarian hyperstimulation
syndrome: A case report documenting the first use of a superior vena caval filter
for upper limb venous thromboembolism in pregnancy, and the difficulties and
complications relating to anticoagulation in antenatal and peri-partum periods.
AB - The management of venous thromboembolism and subsequent pulmonary embolism in
pregnancy remains hugely challenging. In this case, we report the first use of a
superior vena caval filter in pregnancy as an adjunct to pharmacological
anticoagulation. This is the first reported use of a superior vena caval filter
in pregnancy. We discuss the complexities of managing thromboembolism in
pregnancy and the peri-partum period.
PMID- 27512502
TI - Supraventricular tachycardia presenting in labour: A case report achieving
vaginal birth and review of the literature.
AB - Arrhythmias are one of the most common forms of cardiac disease presenting in
pregnancy. Women with underlying arrhythmias may only present to health care
professionals when they are pregnant. The most common type of sustained
arrhythmia presenting in pregnancy is a supraventricular tachycardia (SVT). This
can be difficult to diagnose, as symptoms such as palpitations, dizziness and
shortness of breath are also common symptoms of pregnancy. We present the
management of a woman who developed intrapartum SVT. Her case highlights the
importance of considering the diagnosis in the antenatal period, the use of
antiarrhythmic drugs, as well as the fact that achieving vaginal delivery is
possible in correctly selected cases while the mother and baby remain stable.
PMID- 27512503
TI - The micromorphology of Trichoderma reesei analyzed in cultivations on lactose and
solid lignocellulosic substrate, and its relationship with cellulase production.
AB - BACKGROUND: Trichoderma reesei is the principal producer of cellulolytic enzymes.
Because of the strong influence on the enzyme production, the morphology of the
filamentous fungi is a key parameter for process optimization. For cost-effective
production of cellulolytic enzymes, the cultivation of T. reesei is performed on
lignocellulosic waste streams. These insoluble substrates prevent the application
of the conventional light microscopy for the analysis of fungal morphology. Here,
we present a novel method for the micromorphological analysis based on confocal
laser-scanning microscopy (CLSM) and the computer-aided image analysis. This
method enabled the quantification of the dimensions of the single cell
(intercalary length and cell width) and the degree of branching in cultivations
on the industrially relevant substrates wheat straw and lactose. The
micromorphology of two T. reesei strains, QM9414 and a carbon catabolite
derepressed cre1 knockout mutant (Deltacre1), was analyzed in dependence of
substrate, inoculation method, and agitation velocity. RESULTS: Trichoderma
reesei strain Deltacre1 formed shorter cells (10.09 um) on average and developed
more ramified mycelia (0.36 branches/cell) than strain QM9414 (12.03 um, 0.22
branches/cell). Cultivated on wheat straw, the average cell length of QM9414
(10.87 um) and Deltacre1 (9.74 um) was 10 and 21 % shorter as compared to
reference cultivations on lactose. When inoculation was done with spores as
compared to hyphal biomass, cell lengths of QM9414 (10.97 um) and Deltacre1 (9.10
um) were on average about 20 % shorter. Strain performance was evaluated in
protein concentration and total cellulase activity, which varied between 0.69 and
2.31 FPU/mL for Deltacre1 and between 0.84 and 1.64 FPU/mL for QM9414. The cell
length exhibited slightly negative correlation with the protein (regression
coefficient -0.04 g/(L um), R (2) 0.33) and the cellulase (-0.30 FPU/(mL um), R
(2) 0.53) production. CONCLUSIONS: The dimensions of the single cell of T. reesei
were dependent on strain background, substrate used and process conditions
applied. Micromorphological changes were correlated semi-quantitatively with the
efficiency of enzyme production. In providing a process analytical tool for
enzyme production by T. reesei on lignocellulosic substrate, this study has
relevance for the characterization and optimization of a critical step in the
overall saccharification process.
PMID- 27512504
TI - High-flow nasal oxygen versus noninvasive ventilation for hypoxemic respiratory
failure: Do we know enough?
PMID- 27512505
TI - Rapid shallow breathing index.
AB - Predicting successful liberation of patients from mechanical ventilation has been
a focus of interest to clinicians practicing in intensive care. Various weaning
indices have been investigated to identify an optimal weaning window. Among them,
the rapid shallow breathing index (RSBI) has gained wide use due to its simple
technique and avoidance of calculation of complex pulmonary mechanics. Since its
first description, several modifications have been suggested, such as the serial
measurements and the rate of change of RSBI, to further improve its predictive
value. The objective of this paper is to review the utility of RSBI in predicting
weaning success. In addition, the use of RSBI in specific patient populations and
the reported modifications of RSBI technique that attempt to improve the utility
of RSBI are also reviewed.
PMID- 27512506
TI - Medical thoracoscopy: Analysis on diagnostic yield through 30 years of
experience.
AB - BACKGROUND: Medical thoracoscopy (MT) or pleuroscopy is a procedure performed to
diagnose and treat malignant and benign pleural diseases. Totally 2752
pleuroscopies executed in 1984-2013 in our center were considered in this study.
METHODS: A retrospective observational study was performed. Observational time
was divided into six series of 5 years. We calculated MT diagnostic yield and
analyzed trends of main diseases diagnosed along the time. RESULTS: Along the 30
years population became progressively older. Number of pleuroscopies firstly
increased, then stabilized and decreased in the last 5 years. The overall
diagnostic yield of MT was 71%, increasing from 57% to 79%. The diagnostic yield
was significantly higher in the presence of monolateral pleural effusion. Cancer
represented more than half of diagnosis; tuberculosis was the most common
nonneoplastic disease. The frequency of all cancers, mesothelioma, and lung
cancer increased through the time; tuberculosis first decreased and then
increased. All specimens resulted appropriate during the last 25 years.
CONCLUSION: MT has a great diagnostic yield that can be improved by practice,
permitting to achieve a specific histological diagnosis in about 80% of patients.
Our experience demonstrates that the accurate selection of the patients
undergoing to MT is very important to reach these results.
PMID- 27512507
TI - Smoking among Lebanese medical students: Prevalence and attitudes.
AB - INTRODUCTION: The tobacco epidemic is a major public health threat facing the
world. Tobacco dependence is recognized as the greatest preventable cause of
disease and death. Medical students are in key position influencing future
tobacco cessation programs. OBJECTIVES: The primary objective of this study is to
evaluate the prevalence of smoking among medical students across Lebanon and
their smoking attitudes. It also investigates their attitude toward smoking,
showing where they really stand on this major public health issue. This study
helps better tackle anti-smoking campaigns among both physicians and patients.
METHODS: This cross-sectional study was conducted by sending a questionnaire to
currently enrolled medical students at all seven medical schools in Lebanon. The
32-item questionnaire was used, comprised three sections assessing
sociodemographic characteristics, smoking habits, and attitudes toward smoking
among Lebanese medical students. The questionnaire was launched online on
Limesurvey to retain anonymity. The data were then transferred to Statistical
Package for Social Sciences for analysis. Data were expressed as percentages for
discrete variables and as mean +/- standard deviation for continuous variables.
RESULTS: One hundred sixty-three complete responses remained of the 182 obtained
responses. Forty-two of the total 163 students identified themselves as either
daily or occasional smokers yielding a prevalence of 25.8%. Smokers were less
likely to ask patients about their smoking habit and to counsel them about
smoking cessation. Almost one-third of smokers felt that they had no obligations
toward the society. CONCLUSION: Approximately 1 in 4 Lebanese medical students is
a smoker. Students who smoke are less likely to ask patients about their smoking
habits and to counsel them on smoking cessation. This is a major drawback in the
fight against tobacco. This calls for better education of our future doctors on
smoking cessation to decrease the smoking burden on our Lebanese society and
worldwide.
PMID- 27512508
TI - A 10-year retrospective review of pediatric lung abscesses from a single center.
AB - INTRODUCTION: Pediatric lung abscesses can be primary or secondary, and there is
limited data regarding response to treatments and patient outcomes. OBJECTIVES:
To assess the clinical and microbiologic profile of pediatric patients with lung
abscess and assess the differences in outcomes for patients treated with medical
therapy or medical plus surgical therapy. METHODS: A retrospective review of all
pediatric patients <= 18 years of age that were treated as an inpatient for lung
abscess between the dates of August 2004 and August 2014 was conducted. Patients
were divided into two subgroups based on the need for surgical intervention.
RESULTS: A total of 39 patients with lung abscess (30 treated with medical
therapy alone, 9 also required surgical interventions) were included. Fever,
cough, and emesis were the most common presenting symptoms, and most of the
patients had underlying respiratory (31%) or neurologic disorders (15%).
Staphylococcus aureus was the most common organism in those that had culture
results available, and ceftriaxone with clindamycin was the most common
combination of antibiotics used for treatment. Comparison of medical and surgical
subgroups identified the duration of fever and abscess size as risk factors for
surgical intervention. CONCLUSIONS: Pediatric lung abscesses can be managed with
medical therapy alone in most cases. Presence of prolonged duration of fever and
larger abscess size may be predictive of the need for surgical intervention. Good
clinical response to prolonged therapy with ceftriaxone and clindamycin was
noted.
PMID- 27512509
TI - Comparison of QuantiFERON-TB gold in tube test versus tuberculin skin test for
screening of latent tuberculosis infection in Saudi Arabia: A population-based
study.
AB - OBJECTIVES: To compare QuantiFERON-TB gold in tube (QFT-GIT) test with tuberculin
skin test (TST) in detecting latent tuberculosis infection (LTBI) among a general
population in Saudi Arabia. METHODS: A population-based cross-sectional study was
conducted between July 2010 and March 2013 among individuals randomly selected
from the list of those receiving care at primary healthcare centers in three
provinces of Saudi Arabia; Central, Western, and Eastern provinces. Those younger
than 5 years, immunocompromised, had a current or previous history of active TB,
LTBI, or who were receiving anti-TB medications were excluded. Informed consent
was obtained before the study questionnaire was completed. Participants were then
evaluated for LTBI using QFT-GIT test followed immediately by TST. RESULTS: Of
the 1369 subjects included in the final analysis, QFT-GIT was positive in 124
(9.1%) and TST was positive in 127 (9.3%). Positive concordance was observed in
49 (3.6%) subjects while negative concordance was observed in 1167 (85.2%)
subjects. The overall agreement between the two tests was 88.8% with a
significant kappa (kappa) test (kappa = 0.332, P < 0.001). Concordance was
significantly higher in younger age, female gender, single status, students,
primary education, living in middle-sized families, and never smoked.
CONCLUSIONS: The overall agreement of TST and QFT-GIT for the detection of LTBI
among a Saudi general population was 88.8%. QFT-GIT is probably comparable to TST
for detecting LTBI in an intermediate TB burden country with high at birth
bacille calmette guerin vaccination coverage. Further prospective studies are
needed to compare the ability of both tests to predict TB disease.
PMID- 27512510
TI - A systematic review on prevalence and risk factors associated with treatment-
emergent central sleep apnea.
AB - INTRODUCTION: Treatment-emergent central sleep apnea (TECSA) is the appearance of
central apneas and hypopneas after significant resolution of the obstructive
events has been attained using positive airway pressure (PAP) therapy. The aim of
the study was to determine the prevalence of TECSA and to understand what factors
are associated with its development. METHODS: PubMed, MEDLINE, Scopus, Web of
Science and Cochran Library databases were searched with Mesh headings to locate
studies linking TECSA and obstructive sleep apnea (OSA). RESULTS: Nine studies
were identified that reported the prevalence of TECSA ranging from 5.0% to 20.3%.
Prevalence of TECSA for studies using only full night titration was between 5.0%
and 12.1% where as it was between 6.5% and 20.3% for studies using split-night
polysomnogram. The mean effective continuous PAP (CPAP) setting varied between
7.5 cm and 15.2 cm of water for patients in TECSA group and between 7.4 cm and
13.6 cm of water for the group without TECSA. CONCLUSIONS: The aggregate point
prevalence of TECSA is about 8% with the estimated range varying from 5% to 20%
in patients with untreated OSA. The prevalence tends to be higher for split-night
studies compared to full night titration studies. TECSA can occur at any CPAP
setting although extremely high CPAP settings could increase the likelihood. Male
gender, higher baseline apnea-hypopnea index, and central apnea index at the time
of diagnostic study could be associated with the development of TECSA at a
subsequent titration study.
PMID- 27512511
TI - Association of human leukocyte antigen class II alleles with severe Middle East
respiratory syndrome-coronavirus infection.
AB - BACKGROUND: Middle East Respiratory Syndrome (MERS) is a disease of the lower
respiratory tract and is characterized by high mortality. It is caused by a beta
coronavirus (CoV) referred to as MERS-CoV. Majority of MERS-CoV cases have been
reported from Saudi Arabia. AIM: We investigated the human leukocyte antigen
(HLA) Class II alleles in patients with severe MERS who were admitted in our
Intensive Care Unit. METHODS: A total of 23 Saudi patients with severe MERS-CoV
infection were typed for HLA class II, results were compared with those of 161
healthy controls. RESULTS: Two HLA class II alleles were associated with the
disease; HLA-DRB1*11:01 and DQB1*02:02, but not with the disease outcome.
CONCLUSIONS: Our results suggest that the HLA-DRB1*11:01 and DQB1*02:02 may be
associated with susceptibility to MERS.
PMID- 27512512
TI - Nuss procedure: Technical modifications to ease bending of the support bar and
lateral stabilizer placement.
AB - BACKGROUND: Modifications defined to ease bending of the support bar and lateral
stabilizer placement during minimal invasive repair of pectus excavatum (MIRPE)
have not been reported. We herein report our experience with MIRPE including
several technical modifications. METHODS: A total of 87 patients who underwent
MIRPE were evaluated retrospectively. Technical modifications are (1) a template
drawn preoperatively according to the anthropometric measurements, (2) more
laterally placed thoracal incisions, (3) single existing incision for multiple
support bars, (4) to secure lateral stabilizers to support bar in inverted
position. RESULTS: The mean patient age was 11.2 +/- 3.8 years. The mean
operating time was 63.7 +/- 18.7 min. The mean Haller index was 5.4 +/- 2.1.
Eight patients necessitated two support bars. The support bars were removed in 69
patients after the completion of treatment. Support bars were left in place 26.8
+/- 4.3 months. Final chest contours of the 56 patients were evaluated as 12
months passed after support bar removal and excellent repair results were
determined in 84.2%. CONCLUSION: Preoperative bending of the support bar
according to anthropometric measurements and fixation of the lateral stabilizers
to the support bar in inverted position facilitates bar shaping and lateral
stabilizer placement.
PMID- 27512513
TI - Information technology to improve patient safety: A round table discussion from
the 5(th) International Patient Safety Forum, Riyadh, Saudi Arabia, April 14-16,
2015.
PMID- 27512514
TI - Pulmonary eosinophilia associated to treatment with natalizumab.
AB - Natalizumab (Tysabri((r))) is a leukocytes chemotaxis inhibitor that decreases
the leukocytes passage through the hematoencephalic barrier and it is currently
used in relapsing-remitting forms of multiple sclerosis (MS). We present a
patient with allergic rhinoconjunctivitis diagnosed with MS who started treatment
with natalizumab. She began to show mild asthmatic symptoms until she needed
admission to the hospital due to respiratory insufficiency. Blood tests showed
peripheral eosinophilia and the thoracic computed tomography scan demonstrated
pulmonary infiltrates. The bronchoscopy with the bronchoalveolar lavage resulted
in eosinophilic alveolitis. No evidence of bacterial, fungal and parasitic
infection, connective tissue disease, or vasculitis were observed. After
discontinuation of natalizumab, the patient improved without other treatments. As
MS is a prevalent disease and the use of natalizumab is increasing, we consider
important to point out that this drug can be associated with pulmonary
eosinophilia, especially in patients with allergic rhinoconjunctivitis or asthma.
PMID- 27512515
TI - Adenosine triphosphate-binding cassette member A3 gene mutation in children from
one family from Saudi Arabia.
AB - Mutation in ABCA3, which is adenosine triphosphate-binding cassette member A3, a
member of protein transporter family for phospholipids into the lamellar bodies
during synthesis of surfactant, can cause lung disease related to surfactant
dysfunction with autosomal recessive pattern. We reported three cases from same
family with ABCA3 mutation, their gene, clinical course, and outcomes mentioning
that one patient had successful lung transplantation, one started the process of
the lung transplantation while the third one died during infancy. We concluded
that the patients with ABCA3 gene mutations are increasing in numbers may be due
to the availability of the genetic testing and high index of suspicion among
physicians. Lung transplantation is the definitive treatment, but availability is
limited in our region.
PMID- 27512516
TI - Sarcoidosis presenting with acute respiratory distress syndrome.
PMID- 27512517
TI - Decortication of empyema.
PMID- 27512518
TI - External RNA Controls Consortium Beta Version Update.
AB - Spike-in RNAs are valuable controls for a variety of gene expression
measurements. The External RNA Controls Consortium developed test sets that were
used in a number of published reports. Here we provide an authoritative table
that summarizes, updates, and corrects errors in the test version that ultimately
resulted in the certified Standard Reference Material 2374. We have noted
existence of anti-sense RNA controls in the material, corrected sub-pool
memberships, and commented on control RNAs that displayed inconsistent behavior.
PMID- 27512519
TI - Draft Genome Sequence of Carotenoid Producing Yellow Pigmented Planococcus
maritimus MKU009.
AB - Planococcus maritimus MKU009 is a Gram positive cocci and a moderate halophilic
bacterium isolated from marine water of Pichavaram, South East Coast of India.
Here we report the draft genome of Planococcus maritimus MKU009 with a total size
of 3,251,644 bp with N50 value of 1681571 bp. The overall G+C content of the
genome was 47.27%. The carotenoid producing crtN, crtB, crtP and crtI genes were
located within the first contig of the genome assembly. This genome source will
provide insights into functional genomics of carotenoid production and metabolic
engineering.
PMID- 27512520
TI - Pseudomonas lini Strain ZBG1 Revealed Carboxylic Acid Utilization and Copper
Resistance Features Required for Adaptation to Vineyard Soil Environment: A Draft
Genome Analysis.
AB - Pseudomonas lini strain ZBG1 was isolated from the soil of vineyard in
Zellenberg, France and the draft genome was reported in this study.
Bioinformatics analyses of the genome revealed presence of genes encoding
tartaric and malic acid utilization as well as copper resistance that correspond
to the adaptation this strain in vineyard soil environment.
PMID- 27512521
TI - Gorman revisited: nonparametric conditions for exact linear aggregation.
AB - In the tradition of Afriat (Int Econ Rev 8:67-77, 1967), Diewert (Rev Econ Stud
40:419-425, 1973) and Varian (Econometrica 50:945-972, 1982), we provide a
revealed preference characterisation of exact linear aggregation. This guarantees
that aggregate demand can be written as a function of prices and aggregate income
alone, while abstracting from income-distributional aspects. We also establish
nonparametric conditions for individual consumption to be representable in terms
of Gorman Polar Form preferences. Our results are simple and complement those of
Gorman (1953, 1961). We illustrate the practical usefulness of our results by
means of an empirical application to a Spanish balanced microdata panel. We find
strong evidence against the existence of a limited set of representative agents,
which in turn seems to empirically support the need for (macroeconomic) models
using a continuum of heterogeneous agents.
PMID- 27512522
TI - Leading indicators of mosquito-borne disease elimination.
AB - Mosquito-borne diseases contribute significantly to the global disease burden.
High-profile elimination campaigns are currently underway for many parasites,
e.g., Plasmodium spp., the causal agent of malaria. Sustaining momentum near the
end of elimination programs is often difficult to achieve and consequently
quantitative tools that enable monitoring the effectiveness of elimination
activities after the initial reduction of cases has occurred are needed.
Documenting progress in vector-borne disease elimination is a potentially
important application for the theory of critical transitions. Non-parametric
approaches that are independent of model-fitting would advance infectious disease
forecasting significantly. In this paper, we consider compartmental Ross-McDonald
models that are slowly forced through a critical transition through gradually
deployed control measures. We derive expressions for the behavior of candidate
indicators, including the autocorrelation coefficient, variance, and coefficient
of variation in the number of human cases during the approach to elimination. We
conducted a simulation study to test the performance of each summary statistic as
an early warning system of mosquito-borne disease elimination. Variance and
coefficient of variation were highly predictive of elimination but
autocorrelation performed poorly as an indicator in some control contexts. Our
results suggest that tipping points (bifurcations) in mosquito-borne infectious
disease systems may be foreshadowed by characteristic temporal patterns of
disease prevalence.
PMID- 27512523
TI - The probabilistic no miracles argument.
AB - This paper develops a probabilistic reconstruction of the No Miracles Argument
(NMA) in the debate between scientific realists and anti-realists. The goal of
the paper is to clarify and to sharpen the NMA by means of a probabilistic
formalization. In particular, I demonstrate that the persuasive force of the NMA
depends on the particular disciplinary context where it is applied, and the
stability of theories in that discipline. Assessments and critiques of "the" NMA,
without reference to a particular context, are misleading and should be
relinquished. This result has repercussions for recent anti-realist arguments,
such as the claim that the NMA commits the base rate fallacy (Howson (2000),
Magnus and Callender (Philosophy of Science, 71:320-338, 2004)). It also helps to
explain the persistent disagreement between realists and anti-realists.
PMID- 27512525
TI - Developmental Changes in Mental Rotation: A Dissociation Between Object-Based and
Egocentric Transformations.
AB - The present study was conducted to investigate developmental changes of mental
rotation performance. We compared children, adults, and older adults regarding
their performance in object-based and egocentric transformations. Both children
and older adults showed higher overall reaction times compared to adults. Results
were interpreted against the background of impaired working memory capacity in
both children and older adults. Since mental changes in working memory are
mediated by age differences in cognitive processing speed, cognitive speed is
supposed to be the underlying factor. Regarding both types of transformations, an
advantage of egocentric over object-based human figures was only found in adults
which led us to tentatively propose that children and older adults show deficits
in perspective taking compared to adults.
PMID- 27512526
TI - The Effects of the Amount of Information on Episodic Memory Binding.
AB - The effects of increasing the number of items to be remembered on associative
recognition and cued recall were examined. Thirty participants were asked during
encoding to determine whether two- and three-item stimuli contained natural
objects, artificial objects, or both. In an associative recognition task, the
participants indicated whether the stimuli were identical to those presented
during encoding, were rearranged by exchanging one of the two-item stimuli for
one of the three-item stimuli, or represented a new stimulus. The correctly
identified rearranged item pairs and triads were included in a subsequent cued
recall task in which participants verbally reported the missing item. As the
number of items increased, the discrimination of rearranged stimuli diminished,
but that of identical trials remained the same. Furthermore, the ability to
retrieve the missing item was unaffected. It was concluded that the effect of the
amount of information on binding depends on how the information must be
retrieved.
PMID- 27512527
TI - Do Rare Stimuli Evoke Large P3s by Being Unexpected? A Comparison of Oddball
Effects Between Standard-Oddball and Prediction-Oddball Tasks.
AB - The P3 component of event-related potentials increases when stimuli are rarely
presented. It has been assumed that this oddball effect (rare-frequent
difference) reflects the unexpectedness of rare stimuli. The assumption of
unexpectedness and its link to P3 amplitude were tested here. A standard- oddball
task requiring alternative key-press responses to frequent and rare stimuli was
compared with an oddball-prediction task where stimuli had to be first predicted
and then confirmed by key-pressing. Oddball effects in the prediction task
depended on whether the frequent or the rare stimulus had been predicted. Oddball
effects on P3 amplitudes and error rates in the standard oddball task closely
resembled effects after frequent predictions. This corroborates the notion that
these effects occur because frequent stimuli are expected and rare stimuli are
unexpected. However, a closer look at the prediction task put this notion into
doubt because the modifications of oddball effects on P3 by expectancies were
entirely due to effects on frequent stimuli, whereas the large P3 amplitudes
evoked by rare stimuli were insensitive to predictions (unlike response times and
error rates). Therefore, rare stimuli cannot be said to evoke large P3 amplitudes
because they are unexpected. We discuss these diverging effects of frequency and
expectancy, as well as general differences between tasks, with respect to
concepts and hypotheses about P3b's function and conclude that each discussed
concept or hypothesis encounters some problems, with a conception in terms of
subjective relevance assigned to stimuli offering the most consistent account of
these basic effects.
PMID- 27512528
TI - Phenomenological Characteristics of Autobiographical Memories: Responsiveness to
an Induced Negative Mood State in Those With and Without a Previous History of
Depression.
AB - In this study we investigated the relative accessibility of phenomenological
characteristics in autobiographical memories of 104 students with and without a
previous history of a depression. Participants recalled personal events that were
elicited with cue words and then asked to rate these personal events for a number
of phenomenological characteristics. The characteristics were typicality,
rumination, valence, importance of others, expectancy, desirability, and personal
importance. The effects of previous history of depression (without history or
with previous history of depression) and self-reported mood (pre- and post
negative mood induction) on autobiographical recall was examined by employing a
mixed factor design. Self-reported mood was measured as a manipulation check,
before and after Mood Induction Procedure. Typicality, rumination and personal
importance showed significant interaction effects in those with a history of
depression. Ordinal regression supported the finding that those with a history of
depression had a higher chance of typicality and personal importance than those
without a history of depression. The results indicate that recall of
autobiographical characteristics is in part dependent on induced negative mood
state and on previous history of depression. The findings may prompt future
research into targeted interventions that reduce individual tendencies for
heightened cognitive reactivity in negative mood states for those with a history
of depression.
PMID- 27512529
TI - Interplay Between the Object and Its Symbol: The Size-Congruency Effect.
AB - Grounded cognition suggests that conceptual processing shares cognitive resources
with perceptual processing. Hence, conceptual processing should be affected by
perceptual processing, and vice versa. The current study explored the
relationship between conceptual and perceptual processing of size. Within a pair
of words, we manipulated the font size of each word, which was either congruent
or incongruent with the actual size of the referred object. In Experiment 1a,
participants compared object sizes that were referred to by word pairs. Higher
accuracy was observed in the congruent condition (e.g., word pairs referring to
larger objects in larger font sizes) than in the incongruent condition. This is
known as the size-congruency effect. In Experiments 1b and 2, participants
compared the font sizes of these word pairs. The size-congruency effect was not
observed. In Experiments 3a and 3b, participants compared object and font sizes
of word pairs depending on a task cue. Results showed that perceptual processing
affected conceptual processing, and vice versa. This suggested that the
association between conceptual and perceptual processes may be bidirectional but
further modulated by semantic processing. Specifically, conceptual processing
might only affect perceptual processing when semantic information is activated.
The current study.
PMID- 27512530
TI - Three-Dimensional Printing Based Hybrid Manufacturing of Microfluidic Devices.
AB - Microfluidic platforms offer revolutionary and practical solutions to challenging
problems in biology and medicine. Even though traditional micro/nanofabrication
technologies expedited the emergence of the microfluidics field, recent advances
in advanced additive manufacturing hold significant potential for single-step,
stand-alone microfluidic device fabrication. One such technology, which holds a
significant promise for next generation microsystem fabrication is three
dimensional (3D) printing. Presently, building 3D printed stand-alone
microfluidic devices with fully embedded microchannels for applications in
biology and medicine has the following challenges: (i) limitations in achievable
design complexity, (ii) need for a wider variety of transparent materials, (iii)
limited z-resolution, (iv) absence of extremely smooth surface finish, and (v)
limitations in precision fabrication of hollow and void sections with extremely
high surface area to volume ratio. We developed a new way to fabricate stand
alone microfluidic devices with integrated manifolds and embedded microchannels
by utilizing a 3D printing and laser micromachined lamination based hybrid
manufacturing approach. In this new fabrication method, we exploit the minimized
fabrication steps enabled by 3D printing, and reduced assembly complexities
facilitated by laser micromachined lamination method. The new hybrid fabrication
method enables key features for advanced microfluidic system architecture: (i)
increased design complexity in 3D, (ii) improved control over microflow behavior
in all three directions and in multiple layers, (iii) transverse multilayer flow
and precisely integrated flow distribution, and (iv) enhanced transparency for
high resolution imaging and analysis. Hybrid manufacturing approaches hold great
potential in advancing microfluidic device fabrication in terms of
standardization, fast production, and user-independent manufacturing.
PMID- 27512531
TI - Benchmarking matching color in composite restorations.
AB - The purpose of this study was to investigate the color samples (A2, A3 and B1) of
three different brands of resin composites using dentine masses. 135 discs were
prepared (5 plates for each thickness, color and brand of composite material). A
colorimetric evaluation, using white and black background, was performed just
after preparation. The color was measured corresponding to "Vita" scale and
DeltaL, Deltaa, Deltab and DeltaE values were calculated using a
spectrophotometer. The results showed that Value, Chroma and Hue often differ
even if the same commercial color and same thickness is used. In conclusion, this
study showed that the perfect aesthetics restoration is possible combining
individual abilities, experience and correct techniques.
PMID- 27512532
TI - Utilizations and Perceptions of Emergency Medical Services by Patients with ST
Segments Elevation Acute Myocardial Infarction in Abu Dhabi: A Multicenter Study.
AB - BACKGROUND: Data on the use of emergency medical services (EMS) by patients with
cardiac conditions in the Gulf region are scarce, and prior studies have
suggested underutilization. Patient perception and knowledge of EMS care is
critical to proper utilization of such services. OBJECTIVES: To estimate
utilization, knowledge, and perceptions of EMS among patients with ST-elevation
myocardial infarction (STEMI) in the Emirate of Abu Dhabi. METHODS: We conducted
a multicenter prospective study of consecutive patients admitted with STEMI in
four government-operated hospitals in Abu Dhabi. Semi-structured interviews were
conducted with patients to assess the rationale for choosing their prehospital
mode of transport and their knowledge of EMS services. RESULTS: Of 587 patients
with STEMI (age 51 +/- 11 years, male 95%), only 15% presented through EMS, and
the remainder came via private transport. Over half of the participants (55%)
stated that they did not know the telephone number for EMS. The most common
reasons stated for not using EMS were that private transport was quicker (40%) or
easier (11%). A small percentage of participants (7%) did not use EMS because
they did not think their symptoms were cardiac-related or warranted an EMS call.
Stated reasons for not using EMS did not significantly differ by age, gender, or
primary language of the patients. CONCLUSIONS: EMS care for STEMI is grossly
underutilized in Abu Dhabi. Patient knowledge and perceptions may contribute to
underutilization, and public education efforts are needed to raise their
perception and knowledge of EMS.
PMID- 27512533
TI - One Year Survival in Nigerians with Peripartum Cardiomyopathy.
AB - BACKGROUND: Peripartum cardiomyopathy (PPCM) is common in North-Western Nigeria.
This study aimed to describe the 1-year survival and left ventricular reverse
remodeling (LVRR) in a group of patients with PPCM from three referral hospitals
in Kano, Nigeria. METHODS: PPCM was defined according to recommendations of the
Heart Failure (HF) Association of the European Society of Cardiology Working
Group on PPCM. LVRR was defined as absolute increase in left ventricular ejection
fraction (LVEF) by >=10.0% and decrease in left ventricular (LV) end-diastolic
dimension indexed to body surface area <=33.0 mm/m(2), while recovered LV
systolic function as LVEF >=55%, at 12 months follow-up. RESULTS: A total of 54
newly diagnosed PPCM patients with mean age of 26.6 +/- 6.7 years, presented with
classical features of predominantly left-sided HF and 33 of them qualified for
follow-up. Of the 17 survivors at 12 months, 8 patients (47.1%) satisfied the
criteria for LVRR, of whom 5 (29.4%) had recovered LV systolic function (LVEF
>=55%), but LVRR was not predicted by any variable in the regression models. The
prevalence of normal LV diastolic function increased from 11.1% at baseline to
35.3% at 12 months (P = 0.02). At 1-year follow-up, 41.4% of patients had died
(two-thirds of them within the first 6 months), but mortality was not predicted
by any variable including LVRR. CONCLUSIONS: In Kano, PPCM patients had modest
LVRR but high mortality at 1-year. Further studies should be carried out to
identify reasons for the high mortality and how to curb it.
PMID- 27512534
TI - Pulmonary Embolism in Young Natives of High Altitude.
AB - Thrombotic events are relatively common in high altitude areas and known to occur
in young soldiers working at high altitude without usual risk factors associated
with thrombosis at sea-level. However, till now, cases with thrombotic events
were reported only in lowlanders staying at high altitude. These two cases of
pulmonary embolism demonstrate that thrombotic events can occur in highlanders
after a prolonged stay at the extreme altitude.
PMID- 27512535
TI - Large Saphenous Venous Graft Aneurysm with Right Atrial Fistulous Communication:
Case Report and Review of Literature.
AB - We report a case of a 56-year-old Caucasian man who presented with acute onset of
substernal chest pain at rest with electrocardiogram showing diffuse ST segment
depression. He had coronary artery bypass graft surgery 16 years ago with a left
internal mammary artery graft to the left anterior descending artery and
saphenous vein grafts to the right coronary artery (RCA) and left circumflex
artery. He underwent coronary angiography, which showed two large aneurysms in
the saphenous venous graft (SVG) to the RCA and a venous leak from the aneurysm.
The venous leak was later confirmed with computer tomographic scan to be a
fistulous communication between the SVG and the right atrium. We discuss in
detail about the treatment options of SVG aneurysm.
PMID- 27512536
TI - Endovascular Treatment of Renal Artery Stenosis due to Fibromuscular Dysplasia -
Is Stent Implantation Underused in this Circumstance?
AB - Fibromuscular dysplasia (FMD) is a nonatherosclerotic and noninflammatory
arterial disease that commonly affects the renal and carotid arteries. The
primary target in treating patients with renal artery FMD is the control of blood
pressure in order to prevent end-organ damage, which can be caused by poorly
controlled hypertension. Invasive endovascular treatment should be taken into
consideration both when hypertension cannot be controlled with medication.
According to current opinion, hypertension attributed to renal artery FMD is
often successfully treated solely with percutaneous renal balloon angioplasty
(PRBA), with no requirement for stent implantation under most circumstances.
However, an FMD recurrence after PRBA occurs frequently in these patients.
PMID- 27512537
TI - Takotsubo Cardiomyopathy Associated with Severe Hypothyroidism in an Elderly
Female.
AB - Takotsubo cardiomyopathy, also known as stress cardiomyopathy, is a syndrome that
affects predominantly postmenopausal women. Despite multiple described
mechanisms, intense, neuroadrenergic myocardial stimulation appears to be the
main trigger. Hyperthyroidism, but rarely hypothyroidism, has been described in
association with Takotsubo cardiomyopathy. Herein, we present a case of stress
cardiomyopathy in the setting of symptomatic hypothyroidism.
PMID- 27512538
TI - Transradial Percutaneous Closure of Coronary Artery-Pulmonary Artery Fistula.
PMID- 27512539
TI - Can incorporating art into medical education help medical students become better
doctors?
PMID- 27512540
TI - Framingham Contribution to Cardiovascular Disease.
PMID- 27512541
TI - Female Urethral Duplication: Rare Anomaly with Unusual Presentation.
AB - Urethral duplication (UD) in females is a rare congenital anomaly and requires a
high degree of clinical suspicion for diagnosis. The preoperative evaluation
requires thorough investigations to delineate anatomy which is imperative for
surgical reconstruction to provide excellent functional and cosmetic outcome. We
describe the successful management of a 6-year-old girl with UD (presented as
ambiguous genitalia and urinary incontinence) along with a review of pertinent
literature.
PMID- 27512542
TI - Persistent Mullerian Duct Syndrome with Transverse Testicular Ectopia.
AB - Persistent Mullerian duct syndrome (PMDS) is a rare form of male
pseudohermaphroditism characterized by the presence of Mullerian duct structures
in a normal male with 46, XY karyotype. Transverse testicular ectopia (TTE) is
rare form of testicular ectopia in which two testes are located on one inguinal
side. The opposite scrotum is empty. PMDS with TTE is rare. We report a case of
PMDS with TTE discovered during surgery for a right inguinal hernia in a 25-year
old male.
PMID- 27512543
TI - Single Visit Feeding Appliance for 1-day-old Neonate with Cleft Palate Using Safe
Dental Putty-Gauze Hybrid Impression Technique for Maxillary Impression.
AB - Cleft lip and palate is one of the most common craniofacial anomalies of humans.
Intraoral impression making is the first clinical step in the fabrication of
feeding appliance for infants with oro-nasal communication. It is difficult to
control the flow of the impression material in the cleft area and undercuts in a
child patient. This clinical report presents a simple and safe impression
technique for maxillary impression making in neonates and infants with cleft
palate. A gauze piece was used to confine the impression material during
functional movements of sucking while impression making in an awake child to
avoid the risk of aspiration or swallowing.
PMID- 27512545
TI - Female Urethral Anomalies in Pediatric Age Group: Uncovered.
AB - Female urethral anomalies such as epispadias and hypospadias have been rarely
reported in the literature. Clinical diagnosis of female urethral anomalies is
significant for management. Diagnosis may be missed leading to mismanagement of
the clinical condition. Herein, we report a case of female epispadias and
hypospadias managed by us at Tertiary Care Center.
PMID- 27512544
TI - A Rare Cause of Postprandial Abdominal Pain.
AB - A 49-year-old woman with medical history of polymyalgia rheumatica presented with
3 weeks history of epigastric pain worse after meal. Gallstones, peptic ulcer,
bowel ischemia, bowel obstruction, gastroesophageal reflux disease, chest
pathology, etc., were excluded from the study. Computerized tomography showed a
short stenotic segment at coeliac trunk with poststenotic dilatation of 8 mm.
Ultrasound scan showed peak velocity of 326 cm/s at the coeliac artery. Diagnosis
of median arcuate ligament syndrome was made.
PMID- 27512546
TI - Malignant Transformation of Vagal Nerve Schwannoma in to Angiosarcoma: A Rare
Event.
AB - Schwannomas are benign, rare peripheral nerve sheath tumors that occur in the
head and neck region. Some physicians opt to closely observe cases of schwannoma
of the neck on an outpatient basis rather than to perform radical surgery.
However, there is a possibility, albeit rare, of malignant transformation of a
benign schwannoma. Here, we are reporting the first case from the Indian
subcontinent which was transformed into the angiosarcoma from benign vagal
schwannoma over a long period. A 47-year-old male patient complaining of left
sided neck swelling since last 12 years, swelling was insidious in onset,
gradually progressive very slowly. In last 2 months, the size of the swelling was
suddenly increased. On examination, there was an approximately 6 cm * 6 cm of
size, firm, nodular, well-defined, nontender swelling in the left lateral part of
the neck. Fine-needle aspiration cytology (FNAC) revealed paraganglioma and
magnetic resonance imaging demonstrated very clearly a tumor, its morphology, and
its relation to the surrounding structures, the tumor was thought to be a vagal
schwannoma. Surgery was done, and the whole of the tumor was removed in toto. On
final histopathological diagnosis, the tumor was proved to be angiosarcoma
developed from vagal schwannoma. Postoperative chemotherapy was given but due to
distant metastasis, the patient died. Long standing neck masses can convert into
malignancy as in our case, therefore, work up of the patient should be done
properly. Multiple FNAC should be done because single FNAC can give the false
negative result as in our case. This was our diagnostic drawback not to do
multiple computed tomography guided FNAC.
PMID- 27512547
TI - Intraoperative Development of Tension Pneumocephalus in a Patient Undergoing
Repair of a Cranial-Dural Defect Under Nitrous Oxide Anesthesia.
AB - Rapid buildup of gas within the cranial vault can result in a life-threatening
condition known as "tension pneumocephalus," necessitating immediate surgical
intervention. Nitrous oxide (N2O), a commonly used inhaled anesthetic, is
associated with the development of tension pneumocephalus and its role in
neurosurgical procedures has been debated in the literature. We present a case of
tension pneumocephalus with preexisting pneumocephalus secondary to the usage of
N2O as an inhaled anesthetic. Included is a literature review of studies
discussing the role of N2O in the development of tension pneumocephalus. N2O is
associated with tension pneumocephalus especially in the setting of preexisting
pneumocephalus. Tension pneumocephalus can manifest as Cushing response and
immediate decompression is life-saving. Nitrous oxide should be used cautiously
in neurosurgical procedures, especially with preexisting pneumocephalus.
PMID- 27512548
TI - Propeller Flap for Complex Distal Leg Reconstruction: A Versatile Alternative
when Reverse Sural Artery Flap is Not Feasible.
AB - Reverse sural artery fasciocutaneous flap has become a workhorse for the
reconstruction of distal leg soft tissue defects. When its use is not feasible,
perforator-based propeller flap offers a better, easier, faster, and cheaper
alternative to free flap. We present our experience with two men both aged 34
years who sustained Gustilo 3B injuries from gunshot. The donor area for reversed
sural artery flap was involved in the injuries. They had early debridement,
external fixation, and wound coverage with perforator-based propeller flaps. The
donor sites were covered with skin graft. All flaps survived. There were minor
wound edge ulcers due to the pressure of positioning that did not affect flap
survival and the ulcers healed with conservative management. Perforator-based
propeller flap is a versatile armamentarium for reconstruction of soft tissue
defects of the distal leg in resource-constrained settings, especially when the
donor area for a reverse flow sural flap artery is involved in the injury.
PMID- 27512549
TI - Reduction and Fixation of Unstable Fractures of the Zygomatic Arch: Report of a
Series of Cases.
AB - BACKGROUND: This study evaluated a series of cases of fracture in the zygomatic
arch with displacement of the fractured segment. MATERIALS AND METHODS: This
prospective cohort study was conducted between May 2008 and February 2009. The
study sample which consist of 10 patients of both genders with fractures in the
zygomatic arch. The collection instrument included a specific sheet with data
concerning the patient's age, cause, side of the fracture, type of treatment
performed, recurrence and presence of lesions in the facial nerve. The
radiographic indices of Waters and Hirtz were used. The data were presented by
means of descriptive statistics (absolute and percentage distributions). RESULTS:
Most of the patients were male (90.0%), the most frequent etiology was a
motorcycle accident (70.0%) and the left side was more affected (60.0%). There
was no recurrence in any of the patients examined; however, 1 patient had a
lesion in the facial nerve. The treatment performed for all patients was
reduction and fixation with titanium miniplates. CONCLUSION: Fractures in the
zygomatic arch are more frequent in young male individuals and the most common
cause is a motorcycle accident, with the use of miniplates constituting an
effective treatment without recurrence.
PMID- 27512550
TI - Acute Physiological and Chronic Health Evaluation II Score and its Correlation
with Three Surgical Strategies for Management of Ileal Perforations.
AB - INTRODUCTION: Ileal perforation peritonitis is a common surgical emergency in the
Indian subcontinent and in tropical countries. It is reported to constitute the
fifth common cause of abdominal emergencies due to high incidence of enteric
fever and tuberculosis in these management based on Acute Physiological and
Chronic Health Evaluation II (APACHE II) score. METHODS: The following study was
conducted in the Department of General Surgery, Government Medical College,
Patiala. A total of 57 patients were studied and divided in to Group I, II, and
III. APACHE II score accessed and score between 10 and 19 were blindly randomized
into three procedures primary closure, resection-anastomosis, and ileostomy. The
outcome was compared. RESULTS: Ileal perforations were most commonly observed in
the third and fourth decade of life with male dominance. APACHE II score was
accessed and out of total 57 patients, 6 patients had APACHE II score of 0-9, 48
patients had APACHE II score of 10-19, and 3 patients had APACHE II score of
>=20. In APACHE II score 10-19, 15 patients underwent primary closure, 16
patients underwent resection-anastomosis, and 17 patients underwent ileostomy.
DISCUSSION AND CONCLUSION: Primary closure of perforation is advocated in
patients with single, small perforation (<1 cm) with APACHE II score 10-19
irrespective of duration of perforation. Ileostomy is advocated in APACHE II
score 10-19, where the terminal ileum is grossly inflamed with multiple
perforations, large perforations (>1 cm), fecal peritonitis, matted bowel loops,
intraoperative evidence of caseating lymph nodes, strictures, and an unhealthy
gut due to edema.
PMID- 27512551
TI - Elective Bowel Surgery with or without Prophylactic Nasogastric Decompression: A
Prospective, Randomized Trial.
AB - INTRODUCTION: Routinely postoperative nasogastric decompression was done until
the nasogastric drainage is minimal, reoccurrence of bowel sounds and passing
flatus. But prolonged nasogastric intubation is associated with complications
like basal atelectasis due to poor cough reflux, loss of electrolytes and
increased patient morbidity. AIMS AND OBJECTIVES: To study the need for routine
use of nasogastric tube post operatively in bowel surgeries with reference to (1)
Return of bowel movements (2) Compare the incidence of complications (3) Duration
of hospital stay. METHODOLOGY: 100 patients who underwent elective bowel surgery
were randomized into two groups: Study group (50): Nasogastric tube was removed
immediately after operation or in the recovery room. Control group (50):
Underwent nasogastric tube removal postoperatively after the patient passed
flatus and audible bowel sounds on auscultation. RESULTS: Incidence of
complications were less in the study group i.e., only three patients had
vomiting, and two patients had abdominal distension which lead to postponement of
oral feeds. Most of our control group patients complained of discomfort and
difficulty in coughing and in bringing out sputum, which was the probable cause
for high incidence of pulmonary complications. CONCLUSION: Routine use of the
nasogastric tube adjunct to patient care following bowel surgery may be safely
eliminated.
PMID- 27512552
TI - Anterior Palatal Island Advancement Flap for Bone Graft Coverage: Technical Note.
AB - BACKGROUND: The most important step in bone graft management is soft tissue
coverage. Dehiscence of the wound leads to graft exposure and subsequent
problems. PURPOSE: This study introduces an axial pattern flap for bone graft
coverage in anterior maxilla. PATIENTS AND METHODS: Use of Anterior Palatal
Island Advancement Flap is presented by the authors. It is a mucoperiosteal flap
with axial pattern blood supply, based on nasopalatine artery. It is easy to
raise and predictable. RESULTS: Anterior Palatal Island Advancement Flap was
effective in bone graft coverage in premaxillary edentulous area. CONCLUSION: It
can be used as an aid for bone graft coverage of premaxillary edentulous ridge,
where the need for mucosa is small in width but long in length.
PMID- 27512553
TI - Primary Squamous Cell Carcinoma of Stomach: A Rare Entity - Case Report and Brief
Review of Literature.
AB - Very few case reports of pure squamous cell carcinoma (SCC) of stomach are
available in the world literature. The exact pathology of this uncommon carcinoma
in stomach remains unknown. This is an additional case report of SCC in an
elderly female arising in the gastric antrum. She underwent distal gastrectomy,
gastrojejunostomy and jejunojejunostomy. The histopathology was reported as SCC
of stomach without any adenocarcinomatous component. She had no other source of
extra gastric primary SCC. After surgery, the patient was advised adjuvant
chemotherapy. This is an additional case of primary SCC of stomach.
PMID- 27512554
TI - Echinococcal Cyst of the Pancreas with Cystopancreatic Duct Fistula Successfully
Treated by Partial Cystectomy and Cystogastrostomy.
AB - The primary pancreatic hydatid (echinococcal) cyst is extremely rare with a
reported incidence of <1%. Owing to its rareness and a considerable overlap of
imaging features, a preoperative diagnosis is usually difficult. The dilemma in
confirming this benign diagnosis has often questioned the extent of radical
pancreatic resection. The involvement of pancreatic duct (cystopancreatic duct
fistula) further complicates the management of such cystic lesions. In this
report, we present a case of isolated hydatid cyst of the pancreatic body and
tail communicating with the pancreatic duct. Cystogastrostomy preceded by partial
cystectomy in the same setting has never been reported to date. The patient had
an uneventful postoperative course and follow-up showed no evidence of cyst
recurrence or dissemination. We consider this a safe surgical option in
longstanding large cysts, especially if a cystopancreatic fistula is detected
beforehand. The success of such a procedure however may rely on the size and
thickness of the cyst wall to support this anastomosis.
PMID- 27512555
TI - Negative Response of Phytoestrogens of Pomegranate Flower Extract against
Cisplatin-induced Nephrotoxicity in Female Rats.
PMID- 27512556
TI - Intake of Dietary Supplements and Malnutrition in Patients in Intensive Care
Unit.
AB - BACKGROUND: Malnutrition is prevalent among patients hospitalized in Intensive
Care Units (ICUs) and causes various complications. Dietary supplementation to
provide appropriate nutritional support may reduce the malnutrition and
complications through improvement in nutritional status. This study was carried
out to assess the association between dietary supplementation and malnutrition
among patients in ICUs. METHODS: A case-control study was conducted on 180 male
patients aged 20-60 years in the ICUs of the hospitals in Ahvaz, Iran in 2013.
Data of two groups including 83 patients (cases) who had consumed regular
hospital meals and dietary supplements and 97 patients (controls) who had
received regular hospital meals were compared. Anthropometric measurements,
laboratory values, and dietary intakes were extracted from medical records, and
Maastricht index (MI) was calculated. Data were analyzed using the IBM SPSS
Statistics 21. T-test and paired-sample t-test were used to determine the
difference between groups. RESULTS: Taking supplements increased daily energy
intake, carbohydrate, and protein in case group (n = 83) significantly (P <
0.05). MI changed to 3.1 +/- 3.8 and 4.3 +/- 4.2 in case (n = 83) and control (n
= 97) groups, respectively. Although the MI fell in both groups, it showed a
greater reduction in case group (from 6.3 +/- 5.3 to 3.1 +/- 3.8). CONCLUSIONS:
Since consuming dietary supplements besides the regular hospital meals increased
intake of energy and macronutrients and reduced the MI significantly, it was
concluded that it helped supply nutritional requirements more effectively and
improved the malnutrition in ICU.
PMID- 27512557
TI - Effect of a Trampoline Exercise on the Anthropometric Measures and Motor
Performance of Adolescent Students.
AB - BACKGROUND: Physical exercises can influence some anthropometric and fitness
components differently. The aim of present study was to evaluate how a relatively
long-term training program in 11-14-year-old male Iranian students affects their
anthropometric and motor performance measures. METHODS: Measurements were
conducted on the anthropometric and fitness components of participants (n = 28)
prior to and following the program. They trained 20 weeks, 1.5 h/session with 10
min rest, in 4 times trampoline training programs per week. Motor performance of
all participants was assessed using standing long jump and vertical jump based on
Eurofit Test Battery. RESULTS: The analysis of variance (ANOVA) repeated
measurement test showed a statistically significant main effect of time in calf
girth P = 0.001, fat% P = 0.01, vertical jump P = 0.001, and long jump P = 0.001.
The ANOVA repeated measurement test revealed a statistically significant main
effect of group in fat% P = 0.001. Post hoc paired t-tests indicated statistical
significant differences in trampoline group between the two measurements about
calf girth (t = -4.35, P = 0.001), fat% (t = 5.87, P = 0.001), vertical jump (t =
-5.53, P = 0.001), and long jump (t = -10.00, P = 0.001). CONCLUSIONS: We can
conclude that 20-week trampoline training with four physical activity
sessions/week in 11-14-year-old students seems to have a significant effect on
body fat% reduction and effective results in terms of anaerobic physical fitness.
Therefore, it is suggested that different training model approach such as
trampoline exercises can help students to promote the level of health and motor
performance.
PMID- 27512558
TI - A Proposed Strategy for Research Misconduct Policy: A Review on Misconduct
Management in Health Research System.
AB - BACKGROUND: Today, with the rapid growth of scientific production, research
misconduct has become a worldwide problem. This article is intended to introduce
the successful experience on the management of research paper misconducts in the
field of health research. METHODS: Our aim was to design and develop the strategy
for research misconduct policy. Focusing on the national regulatory system, we
developed a hierarchical model for paper misconduct policy in all the medical
sciences universities and their affiliated research units. RESULTS: Through our
regulatory policy for paper misconduct management, specific protocol was followed
in the field of health research publications through which the capabilities of
covering the four main elements of prevention, investigation, punishment, and
correction have come together. CONCLUSIONS: Considering the proposed strategy,
regarding the strengths and weaknesses, utilization of evaluation tool can be one
of the best strategies to achieving the prospective of health research papers by
2025.
PMID- 27512559
TI - Terminal investment induced by a bacteriophage in a rhizosphere bacterium.
AB - Despite knowledge about microbial responses to abiotic stress, few studies have
investigated stress responses to antagonistic species, such as competitors,
predators and pathogens. While it is often assumed that interacting populations
of bacteria and phage will coevolve resistance and exploitation strategies, an
alternative is that individual bacteria tolerate or evade phage predation through
inducible responses to phage presence. Using the microbial model Pseudomonas
fluorescens SBW25 and its lytic DNA phage SBW25Phi2, we demonstrate the existence
of an inducible response in the form of a transient increase in population growth
rate, and found that the response was induced by phage binding. This response was
accompanied by a decrease in bacterial cell size, which we propose to be an
associated cost. We discuss these results in the context of bacterial ecology and
phage-bacteria co-evolution.
PMID- 27512560
TI - Endoscopic bronchial occlusion with silicone spigots under virtual bronchoscopic
navigation.
AB - A 68-year-old woman with interstitial lung disease related to dermatomyositis and
systemic scleroderma was admitted to our hospital with fever and dyspnoea.
Although the fever was reduced after antibiotic therapy, a left pneumothorax
suddenly occurred on day 27 after admission. A continuous air leak persisted
despite chest drainage with three tubes and repeated pleurodesis. Chest computed
tomography (CT) images showed a cavitary lesion with a pinhole in the left upper
division, which was suspected to be the affected lesion with the air leak.
Virtual bronchoscopic navigation images were constructed from CT data. Bronchial
occlusion with Endobronchial Watanabe Spigots (EWSs) was performed on day 52. Two
medium-sized EWSs were inserted into the left B1 + 2a and B1 + 2b, and the air
leak stopped immediately. No procedure-related adverse events occurred. All three
chest tubes were successfully removed by day 60. This case demonstrates that
virtual bronchoscopic navigation can improve bronchial occlusion procedures using
EWSs.
PMID- 27512561
TI - Herpetic tracheitis in association with rituximab therapy.
AB - A 58-year old lady under active follow-up with the respiratory services at our
institution for bronchiectasis secondary to hypogammaglobulinaemia presented with
hoarseness and haemoptysis. She was also receiving rituximab maintenance therapy
for follicular lymphoma. Bronchoscopy demonstrated vesicular lesions on her vocal
cords and trachea, confirmed as herpes simplex virus (HSV) on cytological
analysis of brushings. She responded well to intravenous valacyclovir. Rituximab
is increasingly utilised in the treatment of haematological and auto-immune
disorders. This case highlights the potential of this drug to potentiate
susceptibility to infection in an already immunocompromised individual.
PMID- 27512562
TI - Role of granulocyte-macrophage colony-stimulating factor in pulmonary fibrosis
following pulmonary alveolar proteinosis.
AB - Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized
by accumulation of lipoproteinacious material in alveoli, with distinct features
on high resolution computed tomography and biopsy. Its association with pulmonary
fibrosis is infrequently encountered, and a clear understanding of the underlying
pathogenesis is yet to be established. We report the case of a 48-year-old woman
with known autoimmune PAP (aPAP) first diagnosed 20 years ago, who presented with
worsening hypoxemia and radiological features consistent with pulmonary fibrosis,
after many years of stable disease. We present a review of previously considered
mechanisms of causation behind such changes, and in particular, postulate the
role of granulocyte-macrophage colony-stimulating factor deficiency in pulmonary
fibrosis seen in aPAP.
PMID- 27512563
TI - Boerhaave's syndrome - tension hydropneumothorax and rapidly developing
hydropneumothorax: two radiographic clues in one case.
AB - Boerhaave's syndrome is a rare and severe condition with high mortality partly
because of its atypical presentation resulting in delayed diagnosis and
management. Diagnostic clues play an important role in the approach to this
syndrome. Here, we report a 48 year-old male patient hospitalized with fever and
left chest pain radiating into the interscapular area. Two chest radiographs
undertaken 22 h apart showed a rapidly developing tension hydropneumothorax. The
amylase level in the pleural fluid was high. The fluid in the chest tube turned
bluish after the patient drank methylene blue. The diagnosis of Boerhaave's
syndrome was suspected based on the aforementioned clinical clues and confirmed
at the operation. The patient recovered completely with the use of antibiotics
and surgical treatment. In this case, we describe key findings on chest
radiographs that are useful in diagnosing Boerhaave's syndrome.
PMID- 27512564
TI - Exercise-induced endobronchial hemorrhage: a rare clinical presentation.
AB - The phenomenon of exercise-induced hemoptysis is still relatively underrecognised
in humans. We report a case of recurrent hemoptysis brought on by vigorous
exercise. A 33-year-old male presented with several episodes of intermittent
fresh small-volume hemoptysis reproducible on vigorous exercise. There was no
other significant medical history other than a past history of testicular tumor,
treated with orchidectomy and adjuvant Bleomycin-based chemotherapy 1 year prior
to onset of symptoms. Computed tomography scan showed no major abnormalities
other than few small bilateral non-specific nodules. Computed tomography
aortogram and pulmonary angiogram, ventilation/perfusion scan, and
echocardiography yielded no significant abnormalities. Infectious, autoimmune
disease, coagulopathy, vasculitis, and malignant causes were excluded.
Bronchoscopy showed possible endobronchial bleeding. This phenomenon is thought
to be due to vulnerability of pulmonary capillaries to stress or mechanical
failure during strenuous exercise at high cardiorespiratory workload.
PMID- 27512565
TI - Appendicitis complicated by appendiceal metastasis via peritoneal dissemination
from lung cancer.
AB - Peritoneal disseminations from lung cancer are difficult to detect during the
patient's clinical course. Therefore, complications of this condition are
unclear. We report a case in which peritoneal dissemination from lung cancer
complicated appendicitis. A 74-year-old man with lung cancer who was receiving
maintenance therapy presented at our hospital because of abdominal pain. It was
the seventh day after the 14th cycle of maintenance therapy with bevacizumab. He
was diagnosed with acute appendicitis. The resected appendix showed acute
appendicitis complicated by appendiceal metastasis from lung cancer.
Adenocarcinoma was observed predominantly in the serous membrane from the neck to
the tail of the appendix. The distribution of the adenocarcinoma was diffuse.
Peritoneal dissemination was considered the route of metastasis. He was admitted
to the palliative care unit 10 months after appendectomy. Appendiceal metastasis
via peritoneal dissemination from lung cancer complicated appendicitis in our
patient who had been receiving bevacizumab.
PMID- 27512566
TI - Descending necrotizing mediastinitis complicating hyperimmunoglobulin E syndrome.
AB - Descending necrotizing mediastinitis (DNM) is a potentially lethal disease that
originates from a deep neck infection (DNI); it is often associated with an
immunocompromised state. Hyperimmunoglobulin E syndrome (HIES) is an extremely
rare complex immune deficiency characterized by recurrent abscesses of
staphylococcal etiology. A rare case of a 34-year-old woman wherein HIES
putatively promoted the development of DNI into DNM is described. She presented
with cervical purulent lymphadenitis and retropharyngeal abscess. Despite
immediate cervical drainage and use of broad-spectrum antibiotics, she developed
DNI and subsequently DNM. Mediastinal drainage with thoracotomy and subsequent
deep neck drainage were performed. Bacterial culture of the abscess isolated
methicillin-resistant Staphylococcus aureus (MRSA). Although a postoperative
recurrent deep neck abscess required a second surgery, we succeeded in
conservative remission of recurrent mediastinal abscess with long-term use of
anti-MRSA drugs. Sufficient drainage under thoracotomy and robust administration
of postoperative antibiotics resulted in successful management of HIES-associated
DNM.
PMID- 27512567
TI - Disseminated cryptococcosis presenting as mediastinal and hilar lymphadenopathy
in an immunocompetent patient.
AB - We herein report a rare case of disseminated cryptococcosis presenting as
mediastinal and hilar lymphadenopathy in a young immunocompetent man. A
previously healthy 26-year-old man presented with persistent headache and
nonproductive cough. Chest computed tomography indicated mediastinal and hilar
lymphadenopathy. Cryptococcal lymphadenitis and meningitis was confirmed by
endobronchial ultrasound-guided transbronchial needle aspiration and central
spinal fluid examination, respectively. He received liposomal amphotericin B and
flucytosine followed by fluconazole and finally improved.
PMID- 27512568
TI - Multicentric Castleman's disease developing during follow-up of sarcoidosis.
AB - Pulmonary sarcoidosis is reported to have complication of lymphoproliferative
disease such as malignant lymphoma, but the complication of multicentric
Castleman's disease (MCD) is rarely reported. In our case of a 60-year-old woman,
bilateral hilar lymphadenopathy was noted in her chest X-ray. We performed a
transbronchial lung biopsy. She was diagnosed as having pulmonary sarcoidosis
(Stage II). The shadow on chest X-ray disappeared without treatment. However,
after 8 years, swelling of the mediastinal and abdominal lymph node, thickened
bronchovascular bundle, and multiple nodular shadows were identified, and a
thoracoscopic lung biopsy was performed. Based on the histopathological findings
and elevated serum interleukin-6 level (75.7 pg/mL), she was diagnosed with
pulmonary sarcoidosis complicated by MCD. When a change in chest X-ray findings
are found during monitoring of pulmonary sarcoidosis, it is important to proceed
with a thoracoscopic lung biopsy, because of the possibility of the rare
complication of MCD.
PMID- 27512569
TI - The effect of X-ray beam distortion on the Edwards Sapien XT(TM) trans-catheter
aortic valve replacement prosthesis.
AB - INTRODUCTION: Profiling the Aortic root perpendicular to the fluoroscopic image
plane will achieve a more successful implant position for trans-catheter aortic
valve replacement (TAVR). This study aimed to investigate whether the divergent
nature of the X-ray beam from the C-arm altered the appearance of the TAVR
device. METHODS: Under bench-top testing, a 23, 26 and 29 mm Edwards Sapien XT
valve was positioned coaxially at the bottom of a fluoroscopic image utilising 22
and 32 cm fields of view (FOV). The table was then moved so that the valve was
positioned at the top of the image. The valve's appearance was scored using a
previously published three tier classification tool (excellent, satisfactory and
poor) and quantified with measurements. The number of degrees of C-arm rotation
that were required to bring the valve back to a coaxial appearance was recorded.
RESULTS: When using the 32 cm FOV, the valve's appearance changes from excellent
to satisfactory. When a 22 cm FOV was used, the change is less marked. More C-arm
rotation is required to bring the appearance back to coaxial with the 32 cm FOV.
CONCLUSION: Not maintaining the valve in the centre of the image can distort the
valves appearance. This has the potential to affect the final implantation depth.
PMID- 27512570
TI - A benchmarking and comparative analysis of emotional intelligence in student and
qualified radiographers: an international study.
AB - INTRODUCTION: Emotional intelligence (EI) has been identified as an important
trait for healthcare students and healthcare professionals alike and is a
predictor of improved work performance and patient satisfaction. In this paper,
we benchmark an international cohort of radiography students and compare their
scores to those of known qualified practitioner and normative data. METHODS: EI
scores were at commencement from radiography degree programmes at four
universities in Australia, Hong Kong, Republic of Ireland and the United Kingdom
using the short form of the trait EI questionnaire (TEIQue-SF), which yields a
Global score and four sub-factors. In total 293 students chose to participate.
RESULTS: For the Australian combined Irish and UK groups, there were significant
differences in Global EI and three of the four sub-factors between students and
qualified radiographers (Australia: students = 5.01, qualified = 5.27; P <= 0.01)
(Irish/UK students = 5.04, qualified = 5.28; P <= 0.01). When compared to the UK
normative data, there was a significant difference for Global EI between the UK
students and the UK norm data set (students = 4.71, normative = 4.99; P <= 0.01).
CONCLUSION: This study provides benchmarking data for an international
radiography student group. The clear differences of higher EI scores for
qualified practicing radiographers when compared to student score opens
discussion of the impact of academic and clinical practicum as a contributing
factor in EI skills development.
PMID- 27512571
TI - Practice patterns of radiation therapy technology in Australia: results of a
national audit.
AB - INTRODUCTION: This article presents the results of a single-day census of
radiation therapy (RT) treatment and technology use in Australia. The primary aim
of the study was to ascertain patterns of RT practice and technology in use
across Australia. These data were primarily collated to inform curriculum
development of academic programs, thereby ensuring that training is matched to
workforce patterns of practice. METHODS: The study design was a census method
with all 59 RT centres in Australia being invited to provide quantitative summary
data relating to patient case mix and technology use on a randomly selected but
common date. Anonymous and demographic-free data were analysed using descriptive
statistics. RESULTS: Overall data were provided across all six Australian States
by 29 centres of a possible 59, yielding a response rate of 49% and representing
a total of 2743 patients. Findings from this study indicate the increasing use of
emerging intensity-modulated radiotherapy (IMRT), image fusion and image-guided
radiation therapy (IGRT) technology in Australian RT planning and delivery
phases. IMRT in particular was used for 37% of patients, indicating a high uptake
of the technology in Australia when compared to other published data. The results
also highlight the resource-intensive nature of benign tumour radiotherapy.
CONCLUSIONS: In the absence of routine national data collection, the single-day
census method offers a relatively convenient means of measuring and tracking RT
resource utilisation. Wider use of this tool has the potential to not only track
trends in technology implementation but also inform evidence-based guidelines for
referral and resource planning.
PMID- 27512572
TI - Transperineal implantation of gold fiducial markers (gold seeds) for prostate
image-guided radiation therapy: a feasible technique associated with a low risk
of complications.
AB - INTRODUCTION: The purpose is to describe the method, safety and efficacy of
transperineal gold seed placement for image-guided radiation therapy. METHODS: An
ethics committee approved database was used to review records of consecutive
patients from October 2008 through December 2013, who underwent transperineal
implantation of three gold markers into the prostate using staged local
anaesthesia and transrectal ultrasound. Seeds were counted on radiographs from CT
simulation, first treatment and last treatment. Retention and use of at least
three markers for kV/kV matching was considered a successful implant. A visual
analogue scale (VAS) pain assessment was performed. SAS was used for data
analysis. RESULTS: Fiducial marker placement was successful for kV/kV matching in
556/581 patients (95.7%). The procedure was aborted due to pain in two patients.
Additional sedation during the procedure was required in two patients.
Complications include urinary infections (2 patients, <0.5%) and transient
haematuria (2 patients, <0.5%). There were no recorded calls requesting
additional pain medication or delays in radiation due to complications. The
number of seeds identified at simulation: 4 (2 patients), 3 (554 patients), 2 (21
patients), 1 (1 patient), 0 (1 patient). One patient with three seeds and two
patients with <2 seeds had cone beam CT instead of kV/kV imaging for image
guidance. No seeds were lost after simulation. The mean visual analogue pain
score associated with transperineal gold seed insertion met patients'
expectations (respectively 4.1 vs. 4.4 P = 0.19). CONCLUSION: Outpatient
transperineal insertion of fiducials avoids the rectum, is effective, convenient,
well tolerated and has few side effects.
PMID- 27512573
TI - The provision of enteral nutritional support during definitive chemoradiotherapy
in head and neck cancer patients.
AB - Combination chemoradiation is the gold standard of management for locally
advanced squamous cell carcinomas of the head and neck. One of the most
significant advantages of this approach to treatment is organ preservation which
may not be possible with radical surgery. Unfortunately, few treatments are
without side-effects and the toxicity associated with combined modality treatment
causes meaningful morbidity. Patients with head and neck cancer (HNC) may have
difficulties meeting their nutritional requirements as a consequence of tumour
location or size or because of the acute toxicity associated with treatment. In
particular, severe mucositis, xerostomia, dysgeusia and nausea and vomiting limit
intake. In addition to this, dysphagia is often present at diagnosis, with many
patients experiencing silent aspiration. As such, many patients will require
enteral nutrition in order to complete chemoradiotherapy (CRT). Feeding occurs
via catheters placed transnasally (nasogastric tubes) or directly into the
stomach through the anterior abdominal wall (percutaneous gastrostomy tubes). In
the absence of clear evidence concerning the superiority of one method over
another, the choice of feeding tube tends to be dependent on clinician and
patient preference. This review examines key issues associated with the provision
of enteral nutritional support during definitive CRT in HNC patients, including
feeding methods, patient outcomes and timing of tube insertion and use.
PMID- 27512574
TI - Adaptive radiation therapy for bladder cancer: a review of adaptive techniques
used in clinical practice.
AB - Significant changes in the shape, size and position of the bladder during
radiotherapy (RT) treatment for bladder cancer have been correlated with high
local failure rates; typically due to geographical misses. To account for this,
large margins are added around the target volumes in conventional RT; however,
this increases the volume of healthy tissue irradiation. The availability of cone
beam computed tomography (CBCT) has not only allowed in-room volumetric imaging
of the bladder, but also the development of adaptive radiotherapy (ART) for
modification of plans to patient-specific changes. The aim of this review is to:
(1) identify and explain the different ART techniques being used in clinical
practice and (2) compare and contrast these different ART techniques to
conventional RT in terms of target coverage and dose to healthy tissue: A
literature search was conducted using EMBASE, MEDLINE and Scopus with the key
words 'bladder, adaptive, radiotherapy/radiation therapy'. 11 studies were
obtained that compared different adaptive RT techniques to conventional RT in
terms of target volume coverage and healthy tissue sparing. All studies showed
superior target volume coverage and/or healthy tissue sparing in adaptive RT
compared to conventional RT. Cross-study comparison between different adaptive
techniques could not be made due to the difference in protocols used in different
studies. However, one study found daily re-optimisation of plans to be superior
to plan of the day technique. The use of adaptive RT for bladder cancer is
promising. Further study is required to assess adaptive RT versus conventional RT
in terms of local control and long-term toxicity.
PMID- 27512575
TI - Synchronous prostate and rectal adenocarcinomas irradiation utilising volumetric
modulated arc therapy.
AB - Cases of synchronous prostate and colorectal adenocarcinomas have been
sporadically reported. There are case reports on patients with synchronous
prostate and rectal cancers treated with external beam radiotherapy alone or
combined with high-dose rate brachytherapy boost to the prostate. Here, we
illustrate a patient with synchronous prostate and rectal cancers treated using
the volumetric arc therapy (VMAT) technique. The patient was treated with radical
radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved
internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was
delivered to the prostate only, using VMAT. Treatment-related toxicities and
follow-up prostate-specific antigen and carcinoembryonic antigen were collected
for data analysis. At 12 months, the patient achieved complete response for both
rectal and prostate cancers without significant treatment-related toxicities.
PMID- 27512576
TI - Letter in response to 'The role of research for advanced practitioners'.
AB - This letter to the Editor is in response to the paper 'Conceptualisation of the
characteristics advanced practitioners in the medical radiation professions' by
Smith et al. and the subsequent letter from Jenny Sim. The writers agree that
research should be explicitly listed in the conceptual model of advanced
practice, and provide some evidence and viewpoints from over a decade of advanced
practice work in Canada.
PMID- 27512577
TI - Letter in response to correspondence on 'Conceptualisation of the characteristics
of advanced practitioners in the medical radiation professions'.
AB - There is ongoing debate on the position of research as an attribute of advanced
practice. This letter highlights some issues to be considered in light of recent
correspondence published in the JMRS.
PMID- 27512579
TI - Acknowledging the peer reviewers of Journal of Medical Radiation Sciences October
2014-September 2015.
PMID- 27512578
TI - Letter in response to 'The conceptual model of advanced practice does include
research'.
AB - This letter refutes the suggestion made the authors of other letters to the
Editor that the proposed model of the characteristics of advanced practitioners
excludes research.
PMID- 27512581
TI - Patients or prisoners? Time to reconsider the voting rights of mentally
disordered offenders.
AB - Although the Representation of the People Act 2000 permits most psychiatric in
patients to register on the electoral register, transferred prisoners and those
admitted to hospital under hospital orders remain disenfranchised by law. This
article clarifies the voting rights of individuals receiving in-patient
psychiatric care and contends that the selective disenfranchisement of some
mentally disordered offenders is problematic, discriminatory and may breach
international human rights law. There are therefore strong arguments for the UK
government to address this long-standing inequality before the next general
election.
PMID- 27512580
TI - A pilot study about infertile men's awareness of their reprotoxic exposures and
the intervention of occupational medicine to assess them.
AB - BACKGROUND: Male infertility related to professional reprotoxic exposure has been
assessed in several studies. Collaboration between occupational physicians and
patients can yield information about the preventive measures that can be taken to
avoid such exposure. The use of preventive measures is determined by the
collaboration between reproductive medicine and occupational medicine and also by
the patient's awareness of reprotoxic occupational exposures. Our andrology
laboratory developed a systematic environmental interview that an occupational
physician administers before semen analysis to assess patients' occupational
reprotoxic chemical and physical exposures. This observational prospective study
evaluated patients' feelings regarding this interview. The main outcome measure
was the participants' score to determine their general reprotoxicant knowledge.
The study also evaluated the patients' satisfaction about the interview with
occupational physician and their attitude about reproductive toxicants. RESULTS:
The mean score for general knowledge of reprotoxicants was 9.6 +/- 2.7/16. The
most frequently underestimated reprotoxic factor was excessive heat (34.7 %
correct responses). In cases of semen parameter abnormalities AND recognized
occupational reprotoxic exposure, 63.2 % of the patients said they would use
individual protective devices, and 55.1 % said they would temporarily adapt their
workstation. Regarding the interview with the laboratory's occupational
physician, 80.7 % considered it moderately or very useful. Of the interviewed
patients, 46.2 % reported having changed their living habits 2 months after the
interview, and 88.5 % were satisfied or very satisfied with the care they
received. All of the respondents said it would be useful to extend the interview
to include their wives. CONCLUSIONS: The data suggest that patients' knowledge
about reprotoxic exposures can be improved, particularly knowledge related to
physical exposure. The vast majority of patients were satisfied with the
introduction of this new collaboration between reproductive and occupational
medicine.
PMID- 27512582
TI - Suicide under crisis resolution home treatment - a key setting for patient
safety.
AB - Recent years have seen a substantial increase in the use of crisis resolution
home treatment (CRHT) teams as an alternative to psychiatric in-patient
admission. We discuss the functions of these services and their effectiveness.
Our research suggests high rates of suicide in patients under CRHT. Specific
strategies need to be developed to improve patient safety in this setting.
PMID- 27512583
TI - Opening the 'black box': liaison psychiatry services and what they actually do.
AB - Aims and method To develop a simple, pragmatic typology to characterise the
nature of liaison interventions delivered by a liaison service in a National
Health Service setting. We carried out a retrospective electronic case-note
review of referrals to a ward-based liaison psychiatry service. Results Three
hundred and forty-four patients were referred to the service over a 12-month
period. Ten different types of liaison interventions were identified, with the
most common interventions being diagnosis (112 patients, 32.6%), medication
management (57 patients, 16.6%), risk assessment and treatment (56 patients,
16.3% each). Mental Health Act work accounted for the greatest number of contacts
per patient (median 7). Clinical implications There are inherent limitations in
any single-site observational study, as site-specific results cannot be
generalised to other liaison services. The intervention categories we developed,
however, are easy to use and will provide a way of comparing and benchmarking the
range of interventions delivered by different liaison psychiatry services.
PMID- 27512584
TI - Colleague and patient appraisal of consultant psychiatrists and the effects of
patient detention on appraisal scores.
AB - Aims and method This paper aims to review colleague and patient feedback from the
10-year period of the operation of the Royal College of Psychiatrists' 360-degree
appraisal system, specifically: (1) examine the overall distribution of ratings;
(2) examine the effect of working primarily with detained patients on patient
feedback, represented by forensic psychiatrists; and (3) look for a relationship
between colleague and patient ratings. Results Data were analysed for 977
participating psychiatrists. Both colleagues and patients rated psychiatrists
overall with high scores. Less than 1% were identified as low scorers, although
there was no relationship between those identified by colleagues or patients.
Colleague and patient feedback scores varied little between subspecialties
including forensic consultants. Clinical implications Psychiatrists in all
subspecialties obtained high scores from colleagues and staff. Working with
detained patients appeared to have little effect on patient ratings.
PMID- 27512585
TI - Service and treatment engagement of people with very late-onset schizophrenia
like psychosis.
AB - Aims and method Electronic patient records were used to investigate the level of
engagement and treatment that patients with very late-onset schizophrenia-like
psychosis (VLOSLP) had with mental health services. Results Of 131 patients
assessed and diagnosed, 63 (48%) were taking antipsychotic treatment at 3 months,
46 (35%) at 6 months and 36 (27%) at 12 months. At discharge from mental health
services, 54% of patients had failed to engage with services or became lost to
follow-up, 18% had engaged with services but were not taking antipsychotic
medication and only 28% were taking treatment. Clinical implications Results
showed that less than half of the patients with VLOSLP were commenced on
antipsychotic treatment and less than a third remained on treatment at 1 year or
at point of discharge. This highlights the need for services to consider being
more assertive in taking potentially effective treatment to this patient group.
PMID- 27512586
TI - Talking therapy groups on acute psychiatric wards: patients' experience of two
structured group formats.
AB - Aims and method We report the results of a clinical audit of patients' reactions
to two types of talking therapy groups facilitated by assistant psychologists and
psychology graduates on three acute wards. Patients' experiences of problem
solving and interpersonal group formats were explored via focus groups and
structured interviews with 29 group participants. Results Both group formats
generated high satisfaction ratings, with benefits related mostly to generic
factors. Clinical implications Adequately trained and supported assistant
psychologists and psychology graduates can provide supportive talking groups that
patients find helpful.
PMID- 27512587
TI - A multidimensional Framework for Routine Outcome Measurement in Liaison
Psychiatry (FROM-LP).
AB - In the field of liaison psychiatry, as in all areas of healthcare, there is an
essential need for well-organised and consistent collection of information on
outcomes, from a range of perspectives. This special article introduces, and
describes the development of, the multidimensional Framework for Routine Outcome
Measurement in Liaison Psychiatry (FROM-LP). This was challenging owing to the
variety of service settings and types of intervention which characterise liaison
psychiatry. Similar challenges may be faced by other specialties and this, along
with the direct relevance of much of the eventual content of the framework, will
broaden the interest of this article.
PMID- 27512588
TI - Intelligent outcome measures in liaison psychiatry: essential even if not
desirable: Commentary on ... a multidimensional Framework for Routine Outcome
Measurement in Liaison Psychiatry (FROM-LP).
AB - Service development is guided by outcome measures that inform service
commissioners and providers. Those in liaison psychiatry should be encouraged to
develop a positive approach that integrates the collection of outcome measures
into everyday clinical practice. The Framework for Routine Outcome Measurement in
Liaison Psychiatry (FROM-LP) is a very useful tool to measure service quality and
clinical effectiveness, using a combination of clinician-rated and patient-rated
outcome measures and patient-rated experience measures. However, it does not
include measures of cost-effectiveness or training activities. The FROM-LP is a
significant step towards developing nationally unified outcome measures.
PMID- 27512589
TI - A history of liaison psychiatry in the UK.
AB - Aims and method To record the development of liaison psychiatry in the UK and to
summarise the current levels of activity. We also highlight the challenges the
specialty may face if it is to develop further. History since the 1970s is
reviewed by early pioneers and those involved in the present day, with a focus on
the key role played by members of the Royal College of Psychiatrists. Results We
describe the development of training guidelines, the publication of joint
documents with other Royal Colleges, establishing international collaborations
and defining service specifications. We emphasise the importance of collaboration
with other medical organisations, and describe successes and pitfalls. Clinical
implications Much has been achieved but challenges remain. Liaison psychiatry has
a potentially important role in improving patient care. It needs to adapt to the
requirements of the current National Health Service, marshal evidence for cost
effectiveness and persuade healthcare commissioners to fund services that are
appropriate for the psychological needs of general hospital patients.
PMID- 27512590
TI - It is time to bring borderline intellectual functioning back into the main fold
of classification systems.
AB - Borderline intellectual functioning is an important and frequently unrecognised
comorbid condition relevant to the diagnosis and treatment of any and all
psychiatric disorders. In the DSM-IV-TR, it is defined by IQ in the 71-84 range.
In DSM-5, IQ boundaries are no longer part of the classification, leaving the
concept without a clear definition. This modification is one of the least
highlighted changes in DSM-5. In this article we describe the history of the
classification of borderline intellectual functioning. We provide information
about it and on the importance of placing it in the right context and in the
right place in future DSM editions and other classification systems such as the
International Classification of Diseases.
PMID- 27512591
TI - Lessons to be learned from the oldest community psychiatric service in the world:
Geel in Belgium.
AB - This article reviews the family foster care model practised in the small Belgian
town of Geel. A historical introduction is followed by a description of a family
foster care project in its current form. Issues are raised as to whether the
current culture of care pathways, managed care, payment by results and an
emphasis on 'cure' are conducive to recovery as promoted by the recovery model.
Finally, the lessons from Geel are summarised and it is argued that there is much
that can be learned from this way of working to support the recovery movement.
PMID- 27512592
TI - Psychiatrists' understanding and use of psychological formulation: a qualitative
exploration.
AB - Aims and method To establish an initial conceptualisation of how psychiatrists
understand and use formulation within adult psychiatry practice. Twelve
psychiatrists took part in semi-structured interviews. Transcripts were analysed
using a constructivist grounded theory methodology. Results Formulation was
conceptualised as an addition to diagnosis, triggered by risk, complexity and a
need for an enhanced understanding. Participants valued collaborative formulation
with psychologists. Multiple contextual factors were perceived to either
facilitate or inhibit the process. Barriers to formulation led to a disjointed
way of working. Clinical implications Findings contribute to an understanding of
formulation within psychiatry training and practice.
PMID- 27512593
TI - Psychiatrists' use of formulation: Commentary on ... Psychiatrists' understanding
and use of psychological formulation.
AB - Both psychologists and psychiatrists are trained to write formulations of their
patients' illnesses, with some differences in how they do this. Psychologists
focus on psychological understanding, while psychiatrists' formulation brings
together aetiology, functioning and a management plan. Mohtashemi et al's study
records how some psychiatrists understand formulation and its usefulness. Time
pressure was an important barrier to making a full formulation, and some believed
the medical role of the psychiatrist was a priority. The study illustrates some
of the challenges facing psychiatrists working in the NHS in terms of maintaining
high clinical standards and a holistic approach to patient care.
PMID- 27512594
TI - Vulnerable patients going to court: a psychiatrist's guide to special measures.
AB - There have been significant changes to how vulnerable people are treated in the
court system, including the introduction of special measures to support people
both as witness and as accused. This paper summarises the use of special measures
and their application to people with mental health diagnoses or cognitive
impairment.
PMID- 27512595
TI - The expansion of the Foundation Programme in psychiatry.
AB - The Broadening the Foundation Programme report has led to an expansion in the
number of psychiatry foundation placements. This change will have far-reaching
benefits for foundation doctors doing psychiatry, no matter what their future
career intentions. Doctors will develop a better understanding of mental illness,
they will improve their communication skills and they will gain experience of
working within multidisciplinary teams. Recruitment into psychiatry is also
likely to improve. The Royal College of Psychiatrists is putting in place a
number of measures to ensure that placements are of a high quality so that
foundation doctors have a good experience of psychiatry.
PMID- 27512597
TI - Julia Bland interviews a group of anonymous (and frank) core trainees in
psychiatry.
PMID- 27512596
TI - Profile: Professor Ian Jones.
PMID- 27512598
TI - Female genital mutilation and mental health: how can research help the victims?
PMID- 27512599
TI - Mental Health Officer status and recruitment in psychiatry.
PMID- 27512600
TI - Authors' reply: psychiatrists' use of formulation.
PMID- 27512602
TI - Preparation, loading, and cytotoxicity analysis of polymer nanotubes from an
ethylene glycol dimethacrylate homopolymer in comparison to multi-walled carbon
nanotubes.
AB - Despite concerns over toxicity, carbon nanotubes have been extensively
investigated for potential applications in nanomedicine because of their small
size, unique properties, and ability to carry cargo such as small molecules and
nucleic acids. Herein, we show that polymer nanotubes can be synthesized quickly
and easily from a homopolymer of ethylene glycol dimethacrylate (EGDMA). The
nanotubes formed via photo-initiated polymerization of the highly functional
prepolymer, inside an anodized aluminium oxide template, have a regular structure
and large internal pore and can be loaded with a fluorescent dye within minutes
representing a simple alternative to multi-walled carbon nanotubes for biomedical
applications.
PMID- 27512601
TI - Cognitive neuroepigenetics: the next evolution in our understanding of the
molecular mechanisms underlying learning and memory?
AB - A complete understanding of the fundamental mechanisms of learning and memory
continues to elude neuroscientists. Although many important discoveries have been
made, the question of how memories are encoded and maintained at the molecular
level remains. To date, this issue has been framed within the context of one of
the most dominant concepts in molecular biology, the central dogma, and the
result has been a protein-centric view of memory. Here we discuss the evidence
supporting a role for neuroepigenetic mechanisms, which constitute dynamic and
reversible, state-dependent modifications at all levels of control over cellular
function, and their role in learning and memory. This neuroepigenetic view
suggests that DNA, RNA and protein each influence one another to produce a
holistic cellular state that contributes to the formation and maintenance of
memory, and predicts a parallel and distributed system for the consolidation,
storage and retrieval of the engram.
PMID- 27512603
TI - Crystal structure of Clostridium difficile toxin A.
AB - Clostridium difficile infection is the leading cause of hospital-acquired
diarrhoea and pseudomembranous colitis. Disease is mediated by the actions of two
toxins, TcdA and TcdB, which cause the diarrhoea, as well as inflammation and
necrosis within the colon1,2. The toxins are large (308 and 270 kDa,
respectively), homologous (47% amino acid identity) glucosyltransferases that
target small GTPases within the host3,4. The multidomain toxins enter cells by
receptor-mediated endocytosis and, upon exposure to the low pH of the endosome,
insert into and deliver two enzymatic domains across the membrane. Eukaryotic
inositol-hexakisphosphate (InsP6) binds an autoprocessing domain to activate a
proteolysis event that releases the N-terminal glucosyltransferase domain into
the cytosol. Here, we report the crystal structure of a 1,832-amino-acid fragment
of TcdA (TcdA1832), which reveals a requirement for zinc in the mechanism of
toxin autoprocessing and an extended delivery domain that serves as a scaffold
for the hydrophobic alpha-helices involved in pH-dependent pore formation. A
surface loop of the delivery domain whose sequence is strictly conserved among
all large clostridial toxins is shown to be functionally important, and is
highlighted for future efforts in the development of vaccines and novel
therapeutics.
PMID- 27512604
TI - Activation of nuclear factor kappa B pathway and reduction of hypothalamic
oxytocin following hypothalamic lesions.
AB - BACKGROUND: Hypothalamic obesity (HO) occurs in patients with tumors and lesions
in the medial hypothalamic region. In this study, a hyperphagic rat model of
combined medial hypothalamic lesions (CMHL) was used to test which specific
inflammatory molecules are involved. METHODS: In order to target specific
homeostatic medial hypothalamic nuclei (arcuate, ventromedial, and dorsomedial
nuclei), male Sprague-Dawley rats (age of 8 weeks, ~250 g body weight) received
four electrolytic lesions or sham surgery. Post-surgery food intake and weight
changes were tracked and hypothalamic gene expression for inflammatory molecules
as well as anorexigenic peptide oxytocin 7 days and 7 months post-surgery were
tested. RESULTS: Seven days post-surgery, average food intake increased by 23%,
and body weight gain had increased by 68%. Toll-like 4 receptor/nuclear factor
kappaB (TLR4/NF-kappaB)-pathway was specifically activated in the mediobasal
hypothalamus (MBH), resulting in 3-fold higher tumor necrosis factor (TNF)-alpha,
10-fold higher interleukin (IL) 1-beta mRNA levels, and higher expression of
suppression of cytokine signaling (SOCS) 3, while oxytocin mRNA levels were
significantly reduced in CMHL rats versus sham surgery rats 7 days post-surgery.
At 7 months, inflammation was less stimulated in MBH of CMHL rats compared to 7
days post-surgery and SOCS 3 as well as oxytocin mRNA levels were comparable
between the two groups. CONCLUSION: Medial hypothalamic lesions are associated
with strong post-surgery hyperphagia and activation of TLR4/NF-kappaB-pathway as
well as reduced expression of oxytocin in the hypothalamus.
PMID- 27512605
TI - Sarcoid reaction: a rare occurrence associated to colon adenocarcinoma (case
report and literature review).
AB - Granulomatous reactions are related to infectious and non infectious diseases,
but more rarely, granulomas may occur in association to malignancies. The
presence of sarcoid-like granulomas in lymph nodes draining malignant tumors is
an uncommon but well known occurrence. However, their presence in the stroma of
malignant tumors is much rarer. We have only found two previous cases reported in
the Japanese and English literature. In this study we report a well
differentiated adenocarcinoma of the right colon associated to a stromal
granulomatous sarcoid-like reaction. Lymph nodes were not involved. The patient
had a clinical history of tuberculosis treated 15 years ago, but there was no
clinical, histomorphological, immunohistochemical or molecular evidence of
disease at the moment of these findings. We have reviewed the literature to find
the keys and the diagnostic challenges posed by granulomatous sarcoid-like
reaction occurring in lymph nodes draining malignant neoplasms, peritumoral
stroma and in other organs far from the primary tumor. The diagnosis of
granulomatous sarcoid-like reactions associated to malignancies can be
challenging and it can only be made after ruling out specific infectious and non
infectious causes of granulomatous inflammation. The mechanisms involved in
granuloma formation, their relationship with demographic and histopathological
features, their possible association with autoimmune disorders, their cytokine
profile and, more importantly, their prognostic significance in each type of
tumor are still unclear and require studies with larger number of patients.
PMID- 27512606
TI - Breast metastasis from recurrent gallbladder adenocarcinoma: a case report with
review of the literature.
AB - Gallbladder adenocarcinoma has a poor prognostic. The leading modes of
dissemination in gallbladder cancer (GBC) are lymphatic, vascular, neural,
intraperitoneal, and intraductal. The most common site of dissemination is liver.
Breast metastasis in GBC is an unusual site of dissemination. Only few cases have
been reported in the literature. We report a rare case of solitary breast
metastasis from recurrent gallbladder carcinoma in light of existing literature.
PMID- 27512607
TI - Aneurysmal subarachnoid hemorrhage prognostic decision-making algorithm using
classification and regression tree analysis.
AB - BACKGROUND: Classification and regression tree analysis involves the creation of
a decision tree by recursive partitioning of a dataset into more homogeneous
subgroups. Thus far, there is scarce literature on using this technique to create
clinical prediction tools for aneurysmal subarachnoid hemorrhage (SAH). METHODS:
The classification and regression tree analysis technique was applied to the
multicenter Tirilazad database (3551 patients) in order to create the decision
making algorithm. In order to elucidate prognostic subgroups in aneurysmal SAH,
neurologic, systemic, and demographic factors were taken into account. The
dependent variable used for analysis was the dichotomized Glasgow Outcome Score
at 3 months. RESULTS: Classification and regression tree analysis revealed seven
prognostic subgroups. Neurological grade, occurrence of post-admission stroke,
occurrence of post-admission fever, and age represented the explanatory nodes of
this decision tree. Split sample validation revealed classification accuracy of
79% for the training dataset and 77% for the testing dataset. In addition, the
occurrence of fever at 1-week post-aneurysmal SAH is associated with increased
odds of post-admission stroke (odds ratio: 1.83, 95% confidence interval: 1.56
2.45, P < 0.01). CONCLUSIONS: A clinically useful classification tree was
generated, which serves as a prediction tool to guide bedside prognostication and
clinical treatment decision making. This prognostic decision-making algorithm
also shed light on the complex interactions between a number of risk factors in
determining outcome after aneurysmal SAH.
PMID- 27512608
TI - Intramedullary cyst formation after removal of multiple intradural spinal
arachnoid cysts: A case report.
AB - BACKGROUND: A rare cause of spinal cord compression is spinal arachnoid cysts.
Symptoms are caused by spinal cord compression, however, asymptomatic patients
have been also reported. Treatment options depend upon symptom severity and
clinical course. CASE DESCRIPTION: We report the case of a 47-year-old patient
who developed an intramedullary arachnoid cyst after removal of an intradural
extramedullary cyst. CONCLUSION: Surgery should be considered early in a
symptomatic disease course. Longstanding medullary compression may reduce the
possibility of neurological recovery as well as secondary complications such as
intramedullary cyst formation.
PMID- 27512610
TI - Adult medulloblastoma: A rare case report and literature review.
AB - BACKGROUND: Medulloblastoma is a highly malignant embryonal tumor which commonly
arises in the cerebellum. It is relatively rare and accounts for less than 2% of
all primary brain tumors. The tumor primarily occurs in childhood; however,
rarely, it may be found in adult population. In addition, medulloblastoma in
adult population shows features which are quite distinct from the pediatric
group. CASE DESCRIPTION: We report the case of a 33-year-old man who presented to
our institution with a history of blurred vision of both eyes for 5 months
preceded by intermittent headache since the previous year. Preoperative
investigation suggested a posterior fossa mass and we suspected an ependymoma.
The patient underwent ventriculoperitoneal shunt and craniotomy tumor removal,
followed by radiotherapy. Histopathological and immunohistochemical examination
were performed, and the results showed a diagnosis of medulloblastoma.
CONCLUSION: This case is exceptional because adult medulloblastoma occurrence in
our center is extremely rare, and the diagnosis can only be established through
histopathological and immunohistochemical studies.
PMID- 27512609
TI - mTORC1 signaling in primary central nervous system lymphoma.
AB - BACKGROUND: Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) acts as a
downstream effector of phosphatidyl-inositol-3 kinase, which is frequently
hyperactivated in glioblastoma multiforme and links to cell signaling in cellular
proliferation, differentiation, metabolism, and survival. Although many studies
have suggested the importance of mTORC1 in tumorigenesis, its role remains
unclear in brain tumors other than glioblastoma. METHODS: In the present study,
we evaluated the activation of mTORC1 in 24 cases of primary central nervous
system lymphoma (PCNSL). RESULTS: Immunohistochemical analysis showed
overexpression of Rheb, which is immediately upstream of mTORC1, in 20 cases of
PCNSL. Immunohistochemical analysis also showed overexpression of phospho-4E-BP1
(Thr37/46) and phospho-S6 (Ser235/236), which are increased after mTORC1
activation as mTORC1 downstream effectors in 17 and 21 cases, respectively.
CONCLUSION: Our data suggest that abnormal activation of the mTORC1 signaling
pathway may cause tumor growth in patients with PCNSL.
PMID- 27512611
TI - Glioblastoma multiforme of the optic chiasm: A rare case of common pathology.
AB - BACKGROUND: Malignant optic and chiasmatic gliomas are extremely rare, and are
classified pathologically as anaplastic astrocytoma or glioblastoma multiforme
(GBM). Approximately 40 cases of optic GBM in adults have been reported in the
literature, and only five of them were described to originate from the optic
chiasm. CASE DESCRIPTION: An 82-year-old male patient with a past medical history
of diabetes mellitus type 2, melanoma, and bladder cancer presented with gradual
vision loss of the left eye in a period of 1 month. After neuro-ophthalmological
examination, the decision of thither magnetic resonance imaging (MRI) studies was
made. It showed a contrast enhancing mass in the region of the optic chiasm. In
this case, imaging study was not enough to establish an accurate diagnosis and a
left pterional craniotomy for biopsy and resection of the optic chiasmal mass was
performed. After histological evaluation of the mass tissue, the diagnosis of GBM
was made. Taking into account the patient's poor condition and unfavorable
prognosis he was moved to inpatient hospice. The patient deceased within 2 months
after surgery. CONCLUSION: Chiasmal GBM is an extremely rare condition where a
biopsy is necessary for accurate diagnosis and optimal treatment. Differential
diagnosis for such lesions can be very difficult and include demyelinating optic
neuritis and non-demyelinating inflammatory optic neuropathy (e.g., sarcoid),
vascular lesions (e.g., cavernoma), compressive lesions of the optic apparatus,
metastatic malignancy, and primary tumors of the anterior optic pathway. The role
of chemotherapy and radiotherapy including novel stereotaxic radiosurgery methods
is still unclear and will need to be evaluated.
PMID- 27512612
TI - Metastatic brain tumor from urothelial carcinoma of the prostatic urethra.
AB - BACKGROUND: Urothelial carcinoma occurs in the bladder, upper urinary tract, and
lower urinary tract, including prostatic urethra. A majority of the reported
cases of intracranial metastasis from urothelial carcinoma originates from the
bladder and upper urinary tract. Brain metastasis from urothelial carcinoma of
the prostatic urethra has not yet been reported in the literature. CASE
DESCRIPTION: A 72-year-old male presented with a metastatic brain tumor and a 3
year history of urothelial carcinoma of the prostatic urethra treated with
cystourethrectomy and chemotherapy with gemcitabine-cisplatin. Pathological
diagnosis for tumor removal was compatible with metastatic brain tumor from
urothelial carcinoma. CONCLUSION: Brain metastasis from urothelial carcinoma of
the prostatic urethra has not yet been reported in the literature. It is an
extremely rare case, however, we should be careful of brain metastasis during
follow-up for urothelial carcinoma in the lower urinary tract.
PMID- 27512613
TI - Multicentric spinal cord and brain glioblastoma without previous craniotomy.
AB - BACKGROUND: Glioblastoma multiforme (GBS) is a highly malignant glioma that
rarely presents as an infratentorial tumor. Multicentric gliomas lesions are
widely separated in site and/or time and its incidence has been reported between
0.15 and 10%. Multicentric gliomas involving supratentorial and infratentorial
region are even more rare. In most cases, infratentorial disease is seen after
surgical manipulation or radiation therapy and is usually located in the
cerebellum or cervical region. CASE REPORT: We present a rare case of symptomatic
multicentric glioma in the brain, fourth ventricle, cervical as well as lumbar
glioblastoma in an adult without previous therapeutic intervention. We also
review the literature of this rare presentation. CONCLUSIONS: This report
suggests that GBM is a diffuse disease; the more extended the disease, the worse
prognosis it has. The management still remains controversial and further studies
are required to understand the prognosis factors of dissemination.
PMID- 27512614
TI - Genomic and expression analysis of transition proteins in Drosophila.
AB - The current study was aimed at analyzing putative protein sequences of the
transition protein-like proteins in 12 Drosophila species based on the reference
sequences of transition protein-like protein (Tpl (94D) ) expressed in Drosophila
melanogaster sperm nuclei. Transition proteins aid in transforming chromatin from
a histone-based nucleosome structure to a protamine-based structure during
spermiogenesis - the post-meiotic stage of spermatogenesis. Sequences were
obtained from NCBI Ref-Seq database using NCBI ORF-Finder (PSI-BLAST). Sequence
alignments and analysis of the amino acid content indicate that orthologs for Tpl
(94D) are present in the melanogaster species subgroup (D. simulans, D.
sechellia, D. erecta, and D. yakuba), D. ananassae, and D. pseudoobscura, but
absent in D. persmilis, D. willistoni, D. mojavensis, D. virilis, and D.
grimshawi. Transcriptome next generation sequence (RNA-Seq) data for testes and
ovaries was used to conduct differential gene expression analysis for Tpl (94D)
in D. melanogaster, D. simulans, D. yakuba, D. ananassae, and D. pseudoobscura.
The identified Tpl (94D) orthologs show high expression in the testes as compared
to the ovaries. Additionally, 2 isoforms of Tpl (94D) were detected in D.
melanogaster with isoform A being much more highly expressed than isoform B.
Functional analyses of the conserved region revealed that the same high mobility
group (HMG) box/DNA binding region is conserved for both Drosophila Tpl (94D) and
Drosophila protamine-like proteins (MST35Ba and MST35Bb). Based on the rigorous
bioinformatic approach and the conservation of the HMG box reported in this work,
we suggest that the Drosophila Tpl (94D) orthologs should be classified as their
own transition protein group.
PMID- 27512615
TI - Principles and Clinical Application of Dual-energy Computed Tomography in the
Evaluation of Cerebrovascular Disease.
AB - Dual-energy computed tomography (DECT) simultaneously acquires images at two X
ray energy levels, at both high- and low-peak voltages (kVp). The material
attenuation difference obtained from the two X-ray energies can be processed by
software to analyze material decomposition and to create additional image
datasets, namely, virtual noncontrast, virtual contrast also known as iodine
overlay, and bone/calcium subtraction images. DECT has a vast array of clinical
applications in imaging cerebrovascular diseases, which includes: (1)
Identification of active extravasation of iodinated contrast in various types of
intracranial hemorrhage; (2) differentiation between hemorrhagic transformation
and iodine staining in acute ischemic stroke following diagnostic and/or
therapeutic catheter angiography; (3) identification of culprit lesions in intra
axial hemorrhage; (4) calcium subtraction from atheromatous plaque for the
assessment of plaque morphology and improved quantification of luminal stenosis;
(5) bone subtraction to improve the depiction of vascular anatomy with more
clarity, especially at the skull base; (6) metal artifact reduction utilizing
virtual monoenergetic reconstructions for improved luminal assessment
postaneurysm coiling or clipping. We discuss the physical principles of DECT and
review the clinical applications of DECT for the evaluation of cerebrovascular
diseases.
PMID- 27512616
TI - Erratum: Percutaneous CT Guided Ablation in the Hepatic Dome: Artificially
Induced Pneumothorax for Safe Transpleural Access.
AB - [This corrects the article on p. 63 in vol. 5, PMID: 26713179.].
PMID- 27512618
TI - The past and present Earth-Moon system: the speed of light stays steady as tides
evolve.
AB - Tides induce a semimajor axis rate of +38.08 +/- 0.19 mm/yr, corresponding to an
acceleration of the Moon's orbital mean longitude of -25.82 +/- 0.13 "/cent2, as
determined by the analysis of 43 yr of Lunar Laser Ranging (LLR) data. The LLR
result is consistent with analyses made with different data spans, different
analysis techniques, analysis of optical observations, and independent knowledge
of tides. Plate motions change ocean shapes, and geological evidence and model
calculations indicate lower rates of tidal evolution for extended past intervals.
Earth rotation has long-term slowing due to tidal dissipation, but it also
experiences variations for times up to about 105 yr due to changes in the moment
of inertia. An analysis of LLR data also tests for any rate of change in either
the speed of light c or apparent mean distance. The result is (-2.8 +/- 3.4)*10
12 /yr for either scale rate or -(dc/dt)/c, or equivalently -1.0 +/- 1.3 mm/yr
for apparent distance rate. The lunar range does not reveal any change in the
speed of light.
PMID- 27512617
TI - Constitutive IFNalpha/beta signaling maintains expression of signaling
intermediaries for efficient cytokine responses.
AB - Interferons (IFNs) are a family of immunoregulatory cytokines with important
roles in anti-viral and anti-tumor responses. Type I and II IFNs bind distinct
receptors and are associated with different stages of the immune response. There
is however, considerable crosstalk between these two cytokines with enhancement
of IFNgamma responses following IFNalpha/beta priming and loss of IFNalpha/beta
receptor (IFNAR) resulting in diminished IFNgamma responses. In this study, we
sought to define the mechanism of crosstalk between the type I and II IFNs. Our
previous reports demonstrated reduced expression of the canonically activated
transcription factor signal transducer and activator of transcription (STAT)1, in
cells lacking the IFNAR alpha chain (IFNAR1). Therefore, we used microarray
analysis to determine whether reconstitution of STAT1 in IFNAR1-deficient cells
was sufficient to restore IFNgamma responses. We identified several biological
pathways, including the MHC class I antigen presentation pathway, in which STAT1
reconstitution was able to significantly rescue IFNgamma-mediated gene regulation
in Ifnar1 (-/-) cells. Notably, we also found that in addition to low basal
expression of STAT1, cells lacking the IFNAR1 also had aberrant expression of
multiple other transcription factors and signaling intermediaries. The studies
described herein demonstrate that basal and regulated expression of signaling
intermediaries is a mechanism for crosstalk between cytokines including type I
and II IFNs.
PMID- 27512619
TI - Cassini/VIMS observes rough surfaces on Titan's Punga Mare in specular
reflection.
AB - Cassini/VIMS high-phase specular observations of Titan's north pole during the
T85 flyby show evidence for isolated patches of rough liquid surface within the
boundaries of the sea Punga Mare. The roughness shows typical slopes of 6 degrees
+/-1 degrees . These rough areas could be either wet mudflats or a wavy sea.
Because of their large areal extent, patchy geographic distribution, and uniform
appearance at low phase, we prefer a waves interpretation. Applying theoretical
wave calculations based on Titan conditions our slope determination allows us to
infer winds of 0.76+/-0.09 m/s and significant wave heights of [Formula: see
text] cm at the time and locations of the observation. If correct, these would
represent the first waves seen on Titan's seas, and also the first
extraterrestrial sea-surface waves in general.
PMID- 27512620
TI - Determination of plasma and leukocyte vitamin C concentrations in a randomized,
double-blind, placebo-controlled trial with Ester-C((r)).
AB - BACKGROUND: Rapid uptake of vitamin C into blood and retention in tissues are
important indicators of the efficacy of vitamin C supplementation and its immune
supporting role. The objective of this study was to evaluate the bioavailability
of vitamin C in plasma (reflective of recent intake) and leukocytes (reflective
of tissue stores and influences on immune function) from a novel vitamin C
formulation, Ester-C((r)). METHODS: The study was a double-blind, placebo
controlled, crossover trial. Thirty-six subjects, 18-60 years of age, were
randomized to receive placebo (PL, 0 mg vitamin C), ascorbic acid (AA, 1000 mg
vitamin C), and Ester-C((r)) (EC, 1000 mg vitamin C). Plasma and leukocyte
vitamin C were measured baseline and at 2, 4, 8 and 24 h postdose. RESULTS: The
concentration and percent change from baseline in plasma were significantly
higher with EC at all time points when compared to PL. No significant differences
between EC and AA were observed in plasma concentration. Maximum plasma
concentration was higher for EC compared to AA (P = 0.039) and PL (P < 0.001).
Plasma area under the curve (AUC0-24h) was higher for EC (P < 0.001) compared to
PL. The concentration change from baseline in leukocyte vitamin C was increased
with EC at 24 h post-dose (P = 0.036) while no significant within-group changes
were observed in AA or PL at any time point. The percent change in leukocyte
vitamin C concentration was higher for EC at 8 and 24 h compared to AA (P = 0.028
and P = 0.034, respectively) and PL (P = 0.042 and P = 0.036, respectively).
CONCLUSIONS: A single dose of EC resulted in favorable percent change in
leukocyte vitamin C concentration compared to AA and PL, indicating EC is
retained longer within leukocytes. Trial registration ClinicalTrials.gov
Identifier NCT01852903.
PMID- 27512621
TI - Weighted K-means support vector machine for cancer prediction.
AB - To date, the support vector machine (SVM) has been widely applied to diverse bio
medical fields to address disease subtype identification and pathogenicity of
genetic variants. In this paper, I propose the weighted K-means support vector
machine (wKM-SVM) and weighted support vector machine (wSVM), for which I allow
the SVM to impose weights to the loss term. Besides, I demonstrate the numerical
relations between the objective function of the SVM and weights. Motivated by
general ensemble techniques, which are known to improve accuracy, I directly
adopt the boosting algorithm to the newly proposed weighted KM-SVM (and wSVM).
For predictive performance, a range of simulation studies demonstrate that the
weighted KM-SVM (and wSVM) with boosting outperforms the standard KM-SVM (and
SVM) including but not limited to many popular classification rules. I applied
the proposed methods to simulated data and two large-scale real applications in
the TCGA pan-cancer methylation data of breast and kidney cancer. In conclusion,
the weighted KM-SVM (and wSVM) increases accuracy of the classification model,
and will facilitate disease diagnosis and clinical treatment decisions to benefit
patients. A software package (wSVM) is publicly available at the R-project
webpage (https://www.r-project.org).
PMID- 27512622
TI - Cardiovascular magnetic resonance evaluation of left ventricular peak filling
rate using steady-state free precession and phase contrast sequences.
AB - BACKGROUND: We investigated a practical method to measure peak filling rate (PFR)
as an indicator of diastolic function of the left ventricle. Ten adult volunteers
underwent cine MR imaging using steady-state free precession (SSFP) and phase
contrast (PC) sequences to measure PFR. Two PC image sets were acquired at the
mitral valve orifice, and PFR was determined from the set with high true temporal
resolution (temporal PC method) or with high spatial resolution (spatial PC
method). SSFP images covering the left ventricle were acquired, and a time-volume
curve was generated around the peak filling phase. PFR was determined using
parabolic curve fitting on the first-derivative curve of the LV time-volume
curve. FINDINGS: PFR values estimated by the PC methods correlated well with
those estimated by the SSFP method, despite apparent underestimation. The
underestimation was smaller for the temporal PC method (12 %) than for the
spatial PC method (28 %). Intra- and inter-observer repeatabilities were better
for the PC methods than for the SSFP method. CONCLUSIONS: PFR measurement by PC
imaging with high true temporal resolution is convenient and offers excellent
repeatability and acceptable accuracy, indicating suitability for clinical use.
PMID- 27512623
TI - A comparison of the clinical effect of two fixation methods on Hoffa fractures.
AB - INTRODUCTION: Hoffa fractures are rare and difficult to treat for orthopaedic
surgeons. The mechanism of injury of Hoffa fracture is still unknown and the
operation approch and fixation method are still controversial. The aim of this
study is to compare the clinical effect between two fixation methods on Hoffa
fractures. CASE DESCRIPTION: From April 2004 to July 2013, we treated eleven
patients (new method group) with Hoffa fracture using the new fixation method
(fixed with intercondylar screw and crossed screws) and sixteen patients
(traditional method group) using the traditional fixation method (fixed with
anteroposteriorly placed screws). All documents from their admission until the
last followup in December 2015 were reviewed, data regarding complications
collected and results were evaluated using the Knee Society Score. DISCUSSION AND
EVALUATION: After an average follow-up period of 27.1 months (range 24-32
months), all fractures had healed. The average healing time of the new method
group was 11.36 weeks (range 9-14 weeks) and the average healing time of the
traditional method group was 11.88 weeks (range 9-14 weeks). According to the
Knee Society Score, the average score of the new method group was 176.36 points
(range 125-199 points), and the average score of the traditional method group was
171.19 points (range 148-197 points). Statistical analysis (t test, t = 0.76, P >
0.05) showed that the difference of both the healing time (t test, t = 0.94, P >
0.05) and the score between these two groups was not significant. CONCLUSIONS:
These results indicate that the new fixation method for Hoffa fracture is as
effective as the traditional method and may provide a new way to treat Hoffa
fractures.
PMID- 27512624
TI - Clinicopathological and prognostic significance of heat shock protein 27 (HSP27)
expression in non-small cell lung cancer: a systematic review and meta-analysis.
AB - Numbers of clinical and experimental investigations have provided increasing
evidences to demonstrate that heat shock protein 27 (HSP27) is a qualified
predictor for many cancers. However, no consensus has been reached on its
clinicopathological and prognostic significance in patients with non-small cell
lung cancer (NSCLC). Therefore, we performed this systematic meta-analysis to
help addressing this issue. PubMed, EMBASE, the Web of Science and China National
Knowledge Infrastructure were searched for full-text literatures met out
eligibility criteria. We determined the odds ratio (OR) and hazard ratio (HR) as
the appropriate summarized statistics for assessments of clinicopathological and
prognostic roles of HSP27, respectively. Q-test and I(2)-statistic were used to
evaluate the level of heterogeneity. Sensitivity analysis was conducted to
examine the stability of overall estimates. Potential publication bias was
detected by Begg's test and Egger's test. Finally, ten articles were identified
to be included into our meta-analysis. The pooled analyses suggested that HSP27
expression was significantly associated with the unfavorable conditions for
differentiation degree, lymphatic metastasis, clinical stage, squamous cell
carcinoma and tumor size. However, HSP27 expression had no significant
relationship to gender, age and smoking status. Meanwhile, pooled HRs indicated
that HSP27 expression could be a predictor for a lower 5-year overall survival
(OS) rate (HR: 1.832; 95 % CI 1.322-2.538; P < 0.001) but not for 1-year OS of
NSCLC (HR: 0.885; 95 % CI 0.140-5.599; P = 0.896). In conclusion, our meta
analysis demonstrates that HSP27 expression may be a strong biomarker to predict
both the poor clinicopathological and prognostic characteristics in patients with
NSCLC.
PMID- 27512625
TI - Modelling and simulation of wood chip combustion in a hot air generator system.
AB - This study focuses on modelling and simulation of horizontal moving bed/grate
wood chip combustor. A standalone finite volume based 2-D steady state Euler
Euler Computational Fluid Dynamics (CFD) model was developed for packed bed
combustion. Packed bed combustion of a medium scale biomass combustor, which was
retrofitted from wood log to wood chip feeding for Tea drying in Sri Lanka, was
evaluated by a CFD simulation study. The model was validated by the experimental
results of an industrial biomass combustor for a hot air generation system in tea
industry. Open-source CFD tool; OpenFOAM was used to generate CFD model source
code for the packed bed combustion and simulated along with an available solver
for free board region modelling in the CFD tool. Height of the packed bed is
about 20 cm and biomass particles are assumed to be spherical shape with constant
surface area to volume ratio. Temperature measurements of the combustor are well
agreed with simulation results while gas phase compositions have discrepancies.
Combustion efficiency of the validated hot air generator is around 52.2 %.
PMID- 27512626
TI - A retrospective evaluation of preoperative anemia in patients undergoing radical
cystectomy for muscle-invasive urothelial urinary bladder cancer, with or without
neoadjuvant chemotherapy.
AB - BACKGROUND AND OBJECTIVE: Neoadjuvant chemotherapy (NAC) can be associated with
anemia, which can lead to more perioperative blood transfusions (PBT). Usage of
PBT is associated with worse oncological outcomes. We evaluated the prevalence of
preoperative anemia (PA) and the effect on hemoglobin levels depending on surgery
timing after NAC. METHODS: A retrospective single-center study with 240
consecutive patients undergoing radical cystectomy (RC) between 2001 and 2014 for
muscle-invasive urothelial carcinoma (MIBC). Anemia was defined according to the
WHO classification (male <= 130 g/L, female <= 120 g/L). Multivariable logistical
regression was used to identify factors associated with PA and Pearson
correlation for evaluating the change in hemoglobin levels depending on surgery
timing. RESULTS: Overall, 128 (53.3 %) patients were anemic pre-RC and 87 (36.3
%) patients received NAC. In a multivariable analysis, age, receipt of NAC,
female gender, and low BMI were independent predictors of PA. In patients
receiving NAC, the time to surgery from the last NAC cycle was correlated with
the change in hemoglobin levels between the initiation of NAC and surgery.
CONCLUSIONS: PA was common in patients undergoing RC for MIBC. Receipt of NAC was
found to be a strong predictor of PA. CLINICAL MESSAGE: The emerging treatment of
cisplatin based neoadjuvant chemotherapy for muscle-invasive bladder cancer,
confers an increased risk for preoperative anemia. In the management of this
malignancy, preoperative anemia renders further attention and focus.
PMID- 27512627
TI - Experimental study of thermal comfort on stab resistant body armor.
AB - PURPOSE: This research aims to investigate the impacts of exercise intensity and
sequence on human physiology parameters and subjective thermal sensation when
wearing stab resistant body armor under daily working conditions in China [26 and
31 degrees C, 45-50 % relative humidity (RH)], and to investigate on the
relationship between subjective judgments and objective parameters. METHODS:
Eight male volunteers were recruited to complete 3 terms of exercises with
different velocity set on treadmill for 90 min at 26 degrees C and 31 degrees
C, 45-50 % RH. In Exercise 1 volunteers were seated during the test. In Exercise
2, volunteers walked with the velocity of 3 km/h in the first 45 min and 6 km/h
in the left 45 min. In Exercise 3, volunteers walked with the velocity of 6 km/h
in the first 45 min and 3 km/h in the left 45 min. The body core temperature,
skin temperature and subjective judgments were recorded during the whole process.
Analysis of variance was performed among all the tests. RESULTS: Individual
discrepancy of Exercise 1 is larger than that of Exercise 2 and 3. On the premise
of the same walking distance and environmental conditions, core temperature in
Exercise 3 is about 0.2 degrees C lower than that in Exercise 2 in the end; and
with the velocity decrease from 6 km/h to 3 km/h in the end, thermal tolerance of
Exercise 3 is about 1 degree lower than that in Exercise 2. Skin temperatures of
human trunk were at least 1 degrees C higher than that of limbs. CONCLUSIONS:
Activity narrows the individual discrepancy on core temperature. Within
experimental conditions, decreasing of intensity at last stage makes the core
temperature lower and the whole process much tolerable. The core temperature is
more sensitive to the external disturbance on the balance of the whole body, and
it can reflect the subjective thermal sensation and physical exertion.
PMID- 27512628
TI - Spectrophotometric determination of Cu(II) in soil and vegetable samples
collected from Abraha Atsbeha, Tigray, Ethiopia using heterocyclic
thiosemicarbazone.
AB - Two selective and sensitive reagents, 2-acetylpyridine thiosemicarbazone (2-APT)
and 3-acetylpyridine thiosemicarbazone (3-APT) were used for the
spectrophotometric determination of Cu(II). Both reagents gave yellowish Cu(II)
complex at a pH range of 8.0-10.0. Beer's law was obeyed for Cu(II)-2-APT and
Cu(II)-3-APT in the concentration range of 0.16-1.3 and 0.44-1.05 ug/mL,
respectively. The molar absorptivity and of Cu(II)-2-APT and Cu(II)-3-APT were
2.14 * 10(4) at 370 nm, and 6.7 * 10(3) L/mol cm at 350 nm, respectively, while
the Sandell's sensitivity were 0.009 and 0.029 ug/cm(2) in that order. The
correlation coefficient of the standard curves of Cu(II)-2-APT and Cu(II)-3-APT
were 0.999 and 0.998, respectively. The detection limit of the Cu(II)-2-APT and
Cu(II)-3-APT methods were 0.053 and 0.147 ug/mL, respectively. The results
demonstrated that the procedure is precise (relative standard deviation <2 %, n =
10). The method was tested for Cu(II) determination in soil and vegetable
samples. Comparisons of the results with those obtained using a flame atomic
absorption spectrophotometer for Cu(II) determination also tested the validity of
the method using paired sample t test at the 0.05 level showing a good agreement
between them.
PMID- 27512629
TI - A new point of view for mosaicplasty in the treatment of focal cartilage defects
of knee joint: honeycomb pattern.
AB - BACKGROUND: A focal full thickness cartilage lesion of knee joint is one of the
commonly seen intraarticular pathologies among the joint cartilage problems.
Osteochondral autograft transfer mosaicplasty is a method which has satisfactory
outcomes among the treatment preferences of cartilage defects. In spite of the
favorable clinical results there are some pitfalls of mosaicplasty treatment
especially in cases of large defects. One of the major problems of the classical
OAT mosaicplasty is the gap spaces between the plugs. The objective of the
present study is to report the early clinical and radiological outcomes and to
evaluate the clinical application of a new hexagonal osteochondral graft system
(HOGS) with the hypothesis of improvement of the OAT mosaicplasty method with the
use of hexagonally shaped plugs. The study has intended to answer two questions.
(1) Does mosaicplasty with the new HOGS has favorable early clinical outcomes?
(2) Is it possible to arrange the osteochondral autografts without leaving gap
spaces by using hexagonal pattern in OAT mosaicplasty? PATIENTS AND METHODS: We
designed a retrospective study to report analysis of early outcomes of the
initial case series of OAT mosaicplasty by using a new HOGS. Six male individuals
with the diagnosis of osteochondral defect and treated with HOGS and reached
sixth month follow-up formed the basis of the study. The clinical status of the
patients were evaluated with IKDC score. The radiological evaluations were
carried out with direct X-rays and magnetic resonance imaging (MRI) studies. The
mosaicplasty procedures were carried out via standard surgical method of
classical OAT mosaicplasty by using the HOGS following a diagnostic arthroscopy
in the same session. The inclusion criteria was a full thickness osteochondral
lesion of femoral condyle between 1.5 and 6 cm(2) and completion of 6 month
follow-ups. The patients having deformities around the knee or major ligament
lesions were excluded. MOCART scoring system was used for the evaluation of
follow-up MRI findings. The clinical status of the patients were evaluated with
IKDC scores. RESULTS: The mean age of the patients was 40.8 (+/-5.2) years and
the mean duration of the symptoms on presentation was 16 (+/-4.3) months. On the
initial MRI studies mean defect area was measured 3.7 cm(2) (+/-0.9) which was
compatible with arthroscopic findings. During the surgical procedures it was
possible to fill the defect area completely. The mean number of plugs in this
series was 4.8 (+/-1.1). We did not faced with insufficient donor reserve problem
in any of the cases. On the sixth month follow-up physical examination there was
no limitation of the knee joint range of motion in the cases. All patients were
able to bear weight on to their operated extremities without pain. The mean
postoperative IKDC score improvement was 70.2 (+/-3.5) which shows significant
improvement compared to preoperative scores. On the control MRI studies the bone
integration of the hexagonal plugs were complete the cartilage continuity of the
articular surfaces were intact and the grafts were well incorporated in all
cases. The mean MOCART score on the 6th month MRI studies was 65.8 (+/-4.1).
CONCLUSION: The early outcomes of OAT mosaicplasty with HOGS are comparable to
studies on the classical mosaicplasty. According to our observations in this
study we can say that the gap space left between the cylindrical plugs can be
solved by using hexagonal prism shaped plugs.
PMID- 27512630
TI - Characterizing and explaining spatio-temporal variation of water quality in a
highly disturbed river by multi-statistical techniques.
AB - Assessing the spatio-temporal variations of surface water quality is important
for water environment management. In this study, surface water samples are
collected from 2008 to 2015 at 17 stations in the Ying River basin in China. The
two pollutants i.e. chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) are
analyzed to characterize the river water quality. Cluster analysis and the
seasonal Kendall test are used to detect the seasonal and inter-annual variations
in the dataset, while the Moran's index is utilized to understand the spatial
autocorrelation of the variables. The influence of natural factors such as
hydrological regime, water temperature and etc., and anthropogenic activities
with respect to land use and pollutant load are considered as driving factors to
understand the water quality evolution. The results of cluster analysis present
three groups according to the similarity in seasonal pattern of water quality.
The trend analysis indicates an improvement in water quality during the dry
seasons at most of the stations. Further, the spatial autocorrelation of water
quality shows great difference between the dry and wet seasons due to sluices and
dams regulation and local nonpoint source pollution. The seasonal variation in
water quality is found associated with the climatic factors (hydrological and
biochemical processes) and flow regulation. The analysis of land use indicates a
good explanation for spatial distribution and seasonality of COD at the sub
catchment scale. Our results suggest that an integrated water quality measures
including city sewage treatment, agricultural diffuse pollution control as well
as joint scientific operations of river projects is needed for an effective water
quality management in the Ying River basin.
PMID- 27512631
TI - KRAS, GNAS, and RNF43 mutations in intraductal papillary mucinous neoplasm of the
pancreas: a meta-analysis.
AB - BACKGROUND: The prevalence and clinical significances of KRAS, GNAS, and RNF43
mutations in patients with pancreatic intraductal papillary mucinous neoplasm
(IPMN) remain elusive. To evaluate the incidence of the gene mutations and
clinicopathologic differences between KRAS and GNAS mutations in pancreatic
cystic lesions, we performed a meta-analysis of published 33 KRAS, 11 GNAS, and 4
RNF43 studies including 1253, 835, and 143 cases, respectively. METHODS: We
pooled the results of relevant studies identified using the PubMed and EMBASE
databases. The effect sizes of outcome parameters were computed by the prevalence
rate, weighted mean difference, or odds ratio (OR) using a random-effects model.
RESULTS: The pooled prevalence of KRAS, GNAS, and RNF43 mutations in IPMN was 61,
56, and 23 %, respectively. The KRAS (OR 7.4 and 71.2) and GNAS (OR 30.2 and
15.3) mutations were more frequently found in IPMNs than in mucinous cystic
neoplasms and in serous cystadenomas, respectively. Of the microscopic subtypes
of IPMN, KRAS and GNAS were frequently mutated in gastric type (OR 2.7, P <
0.001) and intestinal type (OR 3.0, P < 0.001), respectively. KRAS mutation was
infrequently found in high-grade dysplasia lesions of IPMN (OR 0.6, P = 0.032).
GNAS mutation was associated with male (OR 1.9, P = 0.012). CONCLUSIONS: This
meta-analysis supports that KRAS and GNAS mutations could be diagnostic markers
for IPMN. In addition, the frequencies of KRAS and GNAS mutations in IPMNs are
highly variable according to the microscopic duct subtypes, reflecting their
independent roles in the IPMN-adenocarcinoma sequence.
PMID- 27512632
TI - Vegetation greenness modelling in response to interannual precipitation and
temperature changes between 2001 and 2012 in Liao River Basin in Jilin Province,
China.
AB - BACKGROUND: Liao River basin in Jilin Province is the place of origin of the
Dongliao River. This study gives a comprehensive analysis of the vegetation
coverage in the region and provides a potential theoretical basis for ecological
restoration. METHODS: The seasonal variation of vegetation greenness and dynamics
based on the Normalized Difference Vegetation Index (NDVI) in major land cover
types in the region was studied. Analyzing the relationship NDVI, temperature and
rainfall, we derived a set of predictor variables from 2001 to 2012 using the
MODIS Terra level 1 Product (MOD02QKM). RESULTS: The results showed a general
increasing trend in NDVI value in the region, while 34.63 % of the region showed
degradation. NDVI values begin to rise from April when plants are regreening and
they drop in September when temperature are decreasing and the leaves are falling
in the study area and temperature was found decreasing during the period of 2001
2012 while rainfall showed an increasing trend. This model could be used to
observe the change in vegetation greenness and the dynamic effects of temperature
and rainfall. CONCLUSION: This study provided important data for the
environmental protection of the basin area. And we hope to provide scientific
analysis for controlling water and soil erosion, maintaining the sustainable
productivity of land resources, enhancing the treatment of water pollution and
stimulating the virtuous cycle of the ecological system.
PMID- 27512633
TI - Viewing biodiversity through the lens of science...and art!
AB - With global environmental sustainability at the crossroads, approaches are needed
to build an ecologically literate culture for collective societal navigation
through the intricacies of swift environmental change. This paper demonstrates a
transdisciplinary approach, grounded at the intersection between the arts and
sciences, to increase awareness and understanding of the current biodiversity
crisis. It focuses on one aspect of biodiversity, beta diversity, which examines
how sets of animal and plant species differ between habitats. Theory and real
examples of beta diversity of aquatic animal and plant species from dried-out
ponds in Mediterranean Spain are presented in pixelized visuals. These visuals
are artistic expression of and build the prior knowledge about beta diversity,
which is scrutinized subsequently with statistical analyses to support the
artistic approach with an objectively identified and numerically underpinned
presentation of structure in the visuals. The choice to examine beta diversity in
theory and reality first through art and then through science is deliberate.
Combined, these aspects examine biodiversity through an eco-centric, rather than
a species- and habitat centric view, incorporate elements of surprise (how can
aquatic species in dry ecosystems survive), and reduce uncertainty (by providing
a common numerical yardstick for interpreting the visuals). Together they can
optimize a goal-directed learning process in the viewers necessary for making
judgments, inducing affective reactions, and facilitating memory and decision
making. The approach presented here provides an integral qualitative and
quantitative model useful for a broader inductive-deductive education process
towards finding sustainable solutions as our planet moves swiftly to a future
without historical analogue. Combined art-sciences approaches, as the one
presented here, are useful to facilitate citizens' comprehension of the
scientific and potential policy dimensions of environmental change, including
biodiversity problems, especially because it is the general public that bears the
costs of transformation and adaptation measures.
PMID- 27512634
TI - Intelligent decision support algorithm for distribution system restoration.
AB - Distribution system is the means of revenue for electric utility. It needs to be
restored at the earliest if any feeder or complete system is tripped out due to
fault or any other cause. Further, uncertainty of the loads, result in variations
in the distribution network's parameters. Thus, an intelligent algorithm
incorporating hybrid fuzzy-grey relation, which can take into account the
uncertainties and compare the sequences is discussed to analyse and restore the
distribution system. The simulation studies are carried out to show the utility
of the method by ranking the restoration plans for a typical distribution system.
This algorithm also meets the smart grid requirements in terms of an automated
restoration plan for the partial/full blackout of network.
PMID- 27512635
TI - Covariance and crossover matrix guided differential evolution for global
numerical optimization.
AB - Differential evolution (DE) is an efficient and robust evolutionary algorithm and
has wide application in various science and engineering fields. DE is sensitive
to the selection of mutation and crossover strategies and their associated
control parameters. However, the structure and implementation of DEs are becoming
more complex because of the diverse mutation and crossover strategies that use
distinct parameter settings during the different stages of the evolution. A novel
strategy is used in this study to improve the crossover and mutation operations.
The crossover matrix, instead of a crossover operator and its control parameter
CR, is proposed to implement the function of the crossover operation. Meanwhile,
Gaussian distribution centers the best individuals found in each generation based
on the proposed covariance matrix, which is generated between the best individual
and several better individuals. Improved mutation operator based on the crossover
matrix is randomly selected to generate the trial population. This operator is
used to generate high-quality solutions to improve the capability of exploitation
and enhance the preference of exploration. In addition, the memory population is
randomly chosen from previous generation and used to control the search direction
in the novel mutation strategy. Accordingly, the diversity of the population is
improved. Thus, CCDE, which is a novel efficient and simple DE variant, is
presented in this paper. CCDE has been tested on 30 benchmarks and 5 real-world
optimization problems from the IEEE Congress on Evolutionary Computation (CEC)
2014 and CEC 2011, respectively. Experimental and statistical results demonstrate
the effectiveness of CCDE for global numerical and engineering optimization. CCDE
can solve the test benchmark functions and engineering problems more successfully
than the other DE variants and algorithms from CEC 2014.
PMID- 27512636
TI - Non-stationary component extraction in noisy multicomponent signal using
polynomial chirping Fourier transform.
AB - Inspired by track-before-detection technology in radar, a novel time-frequency
transform, namely polynomial chirping Fourier transform (PCFT), is exploited to
extract components from noisy multicomponent signal. The PCFT combines advantages
of Fourier transform and polynomial chirplet transform to accumulate component
energy along a polynomial chirping curve in the time-frequency plane. The
particle swarm optimization algorithm is employed to search optimal polynomial
parameters with which the PCFT will achieve a most concentrated energy ridge in
the time-frequency plane for the target component. The component can be well
separated in the polynomial chirping Fourier domain with a narrow-band filter and
then reconstructed by inverse PCFT. Furthermore, an iterative procedure,
involving parameter estimation, PCFT, filtering and recovery, is introduced to
extract components from a noisy multicomponent signal successively. The
Simulations and experiments show that the proposed method has better performance
in component extraction from noisy multicomponent signal as well as provides more
time-frequency details about the analyzed signal than conventional methods.
PMID- 27512637
TI - Sufficient conditions for oscillation of a nonlinear fractional nabla difference
system.
AB - In this paper, we study the oscillation of nonlinear fractional nabla difference
equations of the form [Formula: see text]where c and alpha are constants,
[Formula: see text] is the Riemann-Liouville fractional nabla difference operator
of order [Formula: see text] is a real number, and [Formula: see text]. Some
sufficient conditions for oscillation are established.
PMID- 27512638
TI - Crowd behavior representation: an attribute-based approach.
AB - In crowd behavior studies, a model of crowd behavior needs to be trained using
the information extracted from video sequences. Most of the previous methods are
based on low-level visual features because there are only crowd behavior labels
available as ground-truth information in crowd datasets. However, there is a huge
semantic gap between low-level motion/appearance features and high-level concept
of crowd behaviors. In this paper, we tackle the problem by introducing an
attribute-based scheme. While similar strategies have been employed for action
and object recognition, to the best of our knowledge, for the first time it is
shown that the crowd emotions can be used as attributes for crowd behavior
understanding. We explore the idea of training a set of emotion-based
classifiers, which can subsequently be used to indicate the crowd motion. In this
scheme, we collect a large dataset of video clips and provide them with both
annotations of "crowd behaviors" and "crowd emotions". We test the proposed
emotion based crowd representation methods on our dataset. The obtained promising
results demonstrate that the crowd emotions enable the construction of more
descriptive models for crowd behaviors. We aim at publishing the dataset with the
article, to be used as a benchmark for the communities.
PMID- 27512639
TI - Effect of skin infiltration with ropivacaine on postoperative pain in patients
undergoing craniotomy.
AB - BACKGROUND: Local anesthetic infiltration has been used to manage postoperative
pain in various surgeries. The present study was aimed to investigate the effect
of skin infiltration with 0.5 % ropivacaine on postoperative pain in patients
undergoing craniotomy. METHODS: One hundred and six patients with ASA I/II
scheduled to undergo elective craniotomy were enrolled during March to November
in 2015 in this prospective, randomized, placebo-controlled, double-blind study.
After the anesthesia induction, skin along the incision was infiltrated with 0.5
% ropicavaine (group R, n = 53) or 0.9 % normal saline (group C, n = 53),
respectively. Morphine was used as rescue analgesic postoperatively. Morphine
consumption during the first 24 postoperative hours was recorded as the primary
outcome, and the time to first rescue requirement was also recorded. Pain was
assessed at 2, 4, 8, 24 h, 7 days, 3 months after surgery by visual analog scale
(VAS). Heart rate and mean arterial pressure were recorded before anesthesia
induction (T1), after anesthesia induction (T2), after scalp infiltration (T3),
during skull drilling (T4), mater cutting (T5) and skin closure (T6). RESULTS:
Morphine consumption during the first 24 postoperative hours was significantly
higher in group C than in group R (13.36 [6.5, 20] vs. 6.3 [0, 10] mg, P < 0.05).
The first time of patients needed rescue analgesic was prolonged in group R as
compared with group C (6.16 [3.4, 8.0] vs. 3.87 [2.3, 4] h, P < 0.05).
Postoperative VAS and hemodynamic signs during the first 24 h showed no
significant difference in two groups. The incidence of persistent pain on 7 days
and 3 months postoperatively had no significant differences between two groups.
Besides one patient (2 %) enduring moderate pain (VAS 4-7) in group C, the number
of patients suffering from mild pain (VAS 1-3) was 17 (33.3 %) in group R and 17
(34 %) in group C 3 months after surgery. CONCLUSION: The results suggest 0.5 %
ropivacaine scalp infiltration before skin incision has favorable analgesic
effect in reducing morphine consumption and prolong the time of first rescue
analgesic requirement after surgery. Trial registration Chinese Clinical Trial
Registry (http://www.chictr.org.cn/) registration number: ChiCTR-IPR-14005717.
PMID- 27512640
TI - A novel mutation in the CDH1 gene in a Spanish family with hereditary diffuse
gastric cancer.
AB - Hereditary diffuse gastric cancer (HDGC) is an inherited form of diffuse type
gastric cancer. Germline CDH1 mutations have been identified in approximately 15
50 % of affected kindred that meet the clinical criteria for HDGC. If any of the
criteria is met the individual is referred to genetic counseling and CDH1 testing
is offered. In this report we present the case of a Spanish family with HDGC
harboring a novel CDH1 mutation. A 47 year-old female with a diagnostic of
gastric adenocarcinoma and some of her relatives were tested. Study of the entire
CDH1 gene, including intron-exon boundaries, by PCR and sequencing and
immunohistochemical determination of the expression of E-cadherin were performed.
A novel heterozygous deletion in exon 9 of CDH1 gene (c.1220_1220delC,
p.P407Qfs10), was found in the proband, one sister and a nephew. It generates a
premature stop codon giving rise to a truncated protein that leads to a
pathogenic variant. Expression of E-cadherin was absent or frankly reduced in the
proband's tumor but normal in tumor cells of great-uncle. After these results,
the sister underwent prophylactic total gastrectomy, and the nephew is under
annual endoscopic surveillance. Personal or familial history of diffuse gastric
cancer, above all at young age, should encourage CDH1 genetic testing. In this
sense, the review of the criteria and the addition in the last guideline of the
recommendation: "other families in which genetic testing may also be considered"
broadens the number of individuals at risk detected. Since there are not reliable
methods for early detection, DGC is usually diagnosed at an advanced stage and
consequently associated with a poorer outcome. Thus, CDH1 mutations detection
contributes to an improvement in diagnosis and therapeutic intervention.
PMID- 27512641
TI - Remediation of copper contaminated soil by using different particle sizes of
apatite: a field experiment.
AB - The particle size of apatite is one of the critical factors that influence the
adsorption of heavy metals on apatite in the remediation of heavy metal
contaminated soils using apatite. However, little research has been done
evaluating the impact of different particle sizes of apatite on immobilization
remediation of heavy metal polluted soils in field. In this study, the adsorption
isothermal experiments of copper on three kinds of apatite was tested, and the
field experiment by using different particle sizes apatite [nano-hydroxyapatite
(NAP), micro-hydroxyapatite (MAP), ordinary particle apatite (OAP)] at a same
dosage of 25.8 t/ha (1.16 %, W/W) was also conducted. Ryegrass was chosen as the
test plant. The ryegrass biomass, the copper contents in ryegrass and the copper
fractionations in soil were determined after field experiments. Results of
adsorption experiments showed that the adsorption amounts of copper on OAP was
the lowest among different particles. The adsorption amounts of copper on MAP was
higher than NAP at high copper equilibrium concentration (>1 mmol L(-1)), an
opposite trend was obtained at low copper concentration (<1 mmol L(-1)). In the
field experiment, we found that the application of different apatites could
effectively increase the soil pH, decrease the available copper concentration in
soil, provide more nutrient phosphate and promote the growth of ryegrass. The
ryegrass biomass and the copper accumulation in ryegrass were the highest in MAP
among all treatments. The effective order of apatite in phytoremediation of
copper contaminated field soil was MAP > NAP > OAP, which was attributed to the
high adsorption capacity of copper and the strong releasing of phosphate by MAP.
PMID- 27512642
TI - Linguistic research in the empirical paradigm as outlined by Mario Bunge.
AB - In view of the critique of the methodology of the dominant interdisciplinary
research involving language studies as the main component, in particular clinical
linguistics, Cummings (Pragmatic disorders. Perspectives in pragmatics,
philosophy and psychology, vol 3. Springer, Dordrecht, 2014) proposes that "It is
perhaps appropriate at this point to move the debate onto non-empirical grounds."
In Cummings (2014: 113) she starts such a debate on the grounds of the philosophy
of language and pragmatics. In this article, I propose to expand that debate by
including the input of the philosophy of science. I start the discussion by
presenting the way one may carry out language research in the paradigm of
empirical sciences from the perspective outlined in Bunge (Scientific research.
Strategy and philosophy. Berlin, Springer, 1967; Method, model and matter
(synthese library). D. Reidel Publishing Company, Dordrecht, 1973; Emergence and
convergence: qualitative novelty and the unity of knowledge. University of
Toronto Press, Toronto, 2003) and constrained by Altmann's (Towards a theory of
language. Glottometrica 1:1-25, 1978) assumption about self-originating and self
regulatory nature of language.
PMID- 27512643
TI - Novel technique of vulvo-vaginal rejuvenation by lipofilling and injection of
combined platelet-rich-plasma and hyaluronic acid: a case-report.
AB - BACKGROUND: To describe a new surgical procedure and its results: the vulvo
vaginal rejuvenation by lipofilling and an injection of combined platelet-rich
plasma (PRP) and hyaluronic acid (HA). Sexual life for women is affected by the
effect of aging and by post partum traumatism. There are no standard non-invasive
treatments to offer to improve the trophic and dimensional alterations of the
vulvo-vaginal area. The surgical procedure consists in a vaginoplasty by
lipofilling of the posterior vaginal wall far from the vascular axes and with an
injection of an injection of combined PRP and HA subcutaneously in the perineum.
To illustrate the technique and evaluate its results, we present the case of a 39
year-old-female with history of episiotomy presented that vaginal laxity
resistant to physical therapy. To assess the results regarding the sexual quality
of life we used the modified Stabbatsberg self-rating scale. FINDINGS: There were
no intra-operative complications with this simple procedure. During follow-up we
observed an improvement in the modified Stabbatsberg scale and a vulvo-perineal
rejuvenation by improving the vaginal trophicity and restoring a normal vaginal
caliber. No post-operative complications occurred. CONCLUSIONS: Vulvo-vaginal
rejuvenation lipofilling and an injection of combined platelet-rich-plasma and
hyaluronic acid is a minimally invasive technique that is safe and easy to
perform. Further studies are necessary to assess more thoroughly the
effectiveness and safety of this procedure and assess medium and long term
results.
PMID- 27512644
TI - Vertebra segmentation based on two-step refinement.
AB - Knowledge of vertebra location, shape, and orientation is crucial in many medical
applications such as orthopedics or interventional procedures. Computed
tomography (CT) offers a high contrast between bone and soft tissues, but
automatic vertebra segmentation remains difficult. Hence, the wide range of
shapes, aging, and degenerative joint disease alterations as well as the variety
of pathological cases encountered in an aging population make automatic
segmentation sometimes challenging. Besides, daily practice implies a need for
affordable computation time. This paper aims to present a new automated vertebra
segmentation method (using a first bounding box for initialization) for CT 3D
data which tackles these problems. This method is based on two consecutive steps.
The first one is a new coarse-to-fine method efficiently reducing the data amount
to obtain a coarse shape of the vertebra. The second step consists in a hidden
Markov chain (HMC) segmentation using a specific volume transformation within a
Bayesian framework. Our method does not introduce any prior on the expected shape
of the vertebra within the bounding box and thus deals with the most frequent
pathological cases encountered in daily practice. We experiment this method on a
set of standard lumbar, thoracic, and cervical vertebrae and on a public dataset,
on pathological cases, and in a simple integration example. Quantitative and
qualitative results show that our method is robust to changes in shapes and
luminance and provides correct segmentation with respect to pathological cases.
PMID- 27512645
TI - AprilTag array-aided extrinsic calibration of camera-laser multi-sensor system.
AB - This paper presents a new algorithm for extrinsically calibrating a multi-sensor
system including multiple cameras and a 2D laser scanner. On the basis of the
camera pose estimation using AprilTag, we design an AprilTag array as the
calibration target and employ a nonlinear optimization to calculate the single
camera extrinsic parameters when multiple tags are in the field of view of the
camera. The extrinsic parameters of camera-camera and laser-camera are then
calibrated, respectively. A global optimization is finally used to refine all the
extrinsic parameters by minimizing a re-projection error. This algorithm is
adapted to the extrinsic calibration of multiple cameras even if there is non
overlapping field of view. For algorithm validation, we have built a micro-aerial
vehicle platform with multi-sensor system to collect real data, and the
experiment results confirmed that the proposed algorithm yields great
performance.
PMID- 27512646
TI - Viscoelasticity of periodontal ligament: an analytical model.
AB - BACKGROUND: Understanding of viscoelastic behaviour of a periodontal membrane
under physiological conditions is important for many orthodontic problems. A new
analytic model of a nearly incompressible viscoelastic periodontal ligament is
suggested, employing symmetrical paraboloids to describe its internal and
external surfaces. METHODS: In the model, a tooth root is assumed to be a rigid
body, with perfect bonding between its external surface and an internal surface
of the ligament. An assumption of almost incompressible material is used to
formulate kinematic relationships for a periodontal ligament; a viscoelastic
constitutive equation with a fractional exponential kernel is suggested for its
description. RESULTS: Translational and rotational equations of motion are
derived for ligament's points and special cases of translational displacements of
the tooth root are analysed. Material parameters of the fractional viscoelastic
function are assessed on the basis of experimental data for response of the
periodontal ligament to tooth translation. A character of distribution of
hydrostatic stresses in the ligament caused by vertical and horizontal
translations of the tooth root is defined. CONCLUSIONS: The proposed model allows
generalization of the known analytical models of the viscoelastic periodontal
ligament by introduction of instantaneous and relaxed elastic moduli, as well as
the fractional parameter. The latter makes it possible to take into account
different behaviours of the periodontal tissue under short- and long-term loads.
The obtained results can be used to determine loads required for orthodontic
tooth movements corresponding to optimal stresses, as well as to simulate bone
remodelling on the basis of changes in stresses and strains in the periodontal
ligament caused by such movements.
PMID- 27512647
TI - Medical Care for Swimmers.
AB - Swimming is one of the most popular sports worldwide. Competitive swimming is one
of the most watched sports during the Olympic Games. Swimming has unique medical
challenges as a result of a variety of environmental and chemical exposures.
Musculoskeletal overuse injuries, overtraining, respiratory problems, and
dermatologic conditions are among the most common problems swimmers encounter.
Although not unique to swimming, overtraining is a serious condition which can
have significant negative impact on swimmers' health and performance. This review
article is an attempt to discuss various issues that a medical team should
consider when caring for swimmers.
PMID- 27512648
TI - Dissecting asthma pathogenesis through study of patterns of cellular traffic
indicative of molecular switches operative in inflammation.
AB - BACKGROUND: Inflammation and degeneration are the two edged swords that impale a
pulmonary system with the maladies like asthma and idiopathic pulmonary fibrosis.
To explore critical role players that orchestrate the etiology and pathogenesis
of these diseases, we used various lung disease models in mice in specific
genetic knockout templates. MATERIALS AND METHODS: Acute and chronic allergic
asthma and idiopathic pulmonary fibrosis model in mouse was developed in various
genetic knockout templates namely alpha4Delta/ Delta(alpha41-/-), beta2-/-, and
alpha4-/- beta2 mice, and the following parameters were measured to assess
development of composite asthma phenotype- (i) airway hyperresponsiveness to
methacholine by measuring lung resistance and compliance by invasive and Penh by
non-invasive plethysmography as well as lung resistance and compliance using
invasive plethysmography, (ii) in situ inflammation status in lung parenchyma and
lung interstitium and also resultant airway remodelling measured by histochemical
staining namely Masson's Trichrome staining and Hematoxylin&Eosin staining, (iii)
formation of metaplastic goblet cells around lung airways by Alcian blue dye,
(iv) measurement of Th1 and Th2 cytokines in serum and bronchoalveolar lavage
fluid (BALf), (v) serum allergen-specific IgE. Specifically, ovalbumin-induced
acute allergic asthma model in mice was generated in WT (wildtype) and KO
(knockout) models and readouts of the composite asthma phenotype viz. airway
hypersensitivity, serum OVA-specific IgE and IgG, Th2 cytokine in bronchoalveolar
lavage fluid (BALf) and lymphocyte cell subsets viz. T, B cells, monocytes,
macrophages, basophils, mast cells and eosinophils (by FACS and morphometry in
H&E stained cell smears) were assessed in addition to lung and lymph node
histology. RESULTS: We noticed a pattern of cellular traffic between bone marrow
(BM)-> peripheral blood (PB) -> lung parenchyma (LP) -> (BALf) in terms of
cellular recruitment of key cell sub-types critical for onset and development of
the diseases which is different for maintenance and exacerbations in chronic
cyclically occurring asthma that leads to airway remodelling. While inflammation
is the central theme of this particular disease, degeneration and shift in
cellular profile, subtly modifying the clinical nature of the disease were also
noted. In addition we recorded the pattern of cell movement between the secondary
lymphoid organs namely, the cervical, axillary, ingunal, and mesenteric lymph
nodes vis-a-vis spleen and their sites of poiesis BM, PB and lung tissue. While
mechanistic role is the chief domain of the integrins (alpha4 i.e. VLA-4 or
alpha4beta1, VCAM-1; beta2 i.e. CD18 or ICAM-1). CONCLUDING REMARKS: The present
paper thoroughly compares and formulates the pattern of cellular traffic among
the three nodes of information throughput in allergic asthma immunobiology,
namely, primary lymphoid organs (PLO), secondary lymphoid organs (SLO), and
tissue spaces and cells where inflammation and degeneration is occurring within
the purview of the disease pathophysiological onset and ancillary signals in the
above models and reports some interesting findings with respect to adult lung
stem cell niches and its resident progenitors and their role in pathogenesis and
disease amelioration.
PMID- 27512649
TI - Partnerships between the faith-based and medical sectors: Implications for
preventive medicine and public health.
AB - Interconnections between the faith-based and medical sectors are multifaceted and
have existed for centuries, including partnerships that have evolved over the
past several decades in the U.S. This paper outlines ten points of intersection
that have engaged medical and healthcare professionals and institutions across
specialties, focusing especially on primary care, global health, and community
based outreach to underserved populations. In a time of healthcare resource
scarcity, such partnerships-involving religious congregations, denominations, and
communal and philanthropic agencies-are useful complements to the work of private
sector medical care providers and of federal, state, and local public health
institutions in their efforts to protect and maintain the health of the
population. At the same time, challenges and obstacles remain, mostly related to
negotiating the complex and contentious relations between these two sectors. This
paper identifies pressing legal/constitutional, political/policy,
professional/jurisdictional, ethical, and research and evaluation issues that
need to be better addressed before this work can realize its full potential.
PMID- 27512650
TI - A brief measure of Smokers' knowledge of lung cancer screening with low-dose
computed tomography.
AB - We describe the development and psychometric properties of a new, brief measure
of smokers' knowledge of lung cancer screening with low-dose computed tomography
(LDCT). Content experts identified key facts smokers should know in making an
informed decision about lung cancer screening. Sample questions were drafted and
iteratively refined based on feedback from content experts and cognitive testing
with ten smokers. The resulting 16-item knowledge measure was completed by 108
heavy smokers in Houston, Texas, recruited from 12/2014 to 09/2015. Item
difficulty, item discrimination, internal consistency and test-retest reliability
were assessed. Group differences based upon education levels and smoking history
were explored. Several items were dropped due to ceiling effects or overlapping
constructs, resulting in a 12-item knowledge measure. Additional items with high
item uncertainty were retained because of their importance in informed decision
making about lung cancer screening. Internal consistency reliability of the final
scale was acceptable (KR-20 = 0.66) and test-retest reliability of the overall
scale was 0.84 (intraclass correlation). Knowledge scores differed across
education levels (F = 3.36, p = 0.04), while no differences were observed between
current and former smokers (F = 1.43, p = 0.24) or among participants who met or
did not meet the 30-pack-year screening eligibility criterion (F = 0.57, p =
0.45). The new measure provides a brief, valid and reliable indicator of smokers'
knowledge of key concepts central to making an informed decision about lung
cancer screening with LDCT, and can be part of a broader assessment of the
quality of smokers' decision making about lung cancer screening.
PMID- 27512651
TI - The Office Guidelines Applied to Practice program improves secondary prevention
of heart disease in Federally Qualified Healthcare Centers.
AB - The burden of cardiovascular disease (CVD) among minority and low-income
populations is well documented. This study aimed to assess the impact of patient
activation and shared decision-making (SDM) on medication use through the Office
Guidelines Applied to Practice (Office-GAP) intervention in Federally Qualified
Healthcare Centers (FQHCs). Patients (243) with diabetes and CHD participated in
Office-GAP between October 2010 and March 2014. Two-site (FQHCs)
intervention/control design. Office-GAP integrates health literacy, communication
skills education for patients and physicians, decision support tools, and SDM
into routine care. MAIN MEASURES: 1) implementation rates, 2) medication use at
baseline, 3, 6, and 12 months, and 3) predictors of medication use. Logistic
regression with propensity scoring assessed impact on medication use.
Intervention arm had 120 and control arm had 123 patients. We found that program
elements were consistently used. Compared to control, the Office-GAP program
significantly improved medications use from baseline: ACEIs or ARBs at 3 months
(OR 1.88, 95% CI = 1.07; 3.30, p < 0.03), 6 months (OR 2.68, 95% CI = 1.58;4.54;
p < 0.01); statin at 3 months (OR 2.00, 95% CI = 0.1.22; 3.27; p < 0.05), 6
months (OR 3.05, 95% CI = 1.72; 5.43; p < 0.01), Aspirin and/or clopidogrel at 3
months OR 1.59, 95% CI = 1.02, 2.48; p < 0.05), 6 months (OR 3.67, 95% CI = 1.67;
8.08; p < 0.01). Global medication adherence was predicted only by Office-GAP
intervention presence and hypertension. Office-GAP resulted in increased use of
guideline-based medications for secondary CVD prevention in underserved
populations. The Office-GAP program could serve as a model for implementing
guideline-based care for other chronic diseases.
PMID- 27512652
TI - Unravelling the Glasgow effect: The relationship between accumulative bio-
psychosocial stress, stress reactivity and Scotland's health problems.
AB - To date, multiple hypotheses have been proposed for the Scottish effect and, more
specifically, Glasgow's high mortality rate and the associated Glasgow effect.
Previous authors have highlighted the improbability of a single factor as
responsible for this effect with seventeen possible hypotheses presented. These
have ranged from socio-economic factors, lifestyle and cultural factors such as
sectarianism, and political and economic factors. Although these may all be
contributory factors to this paradox, the underpinning reasons for the observed
effect remain relatively unexplained. In this paper, we suggest that the
compounding effect of a unique blend of accumulating life stressors may
predispose Scots, and particularly socially-disadvantaged Glaswegians, to a wide
range of health disorders. In short, a confluence of social, environmental,
attitudinal and cultural stressors perhaps combine to negatively influence
biological health. Future directions should consider the stress remediating role
of physical activity, and the problems presented by barriers to participation in
physical activity and exercise during key transitional stages of life.
PMID- 27512654
TI - The predictors to medication adherence among adults with diabetes in the United
Arab Emirates.
AB - BACKGROUND: Diabetes is a chronic medical condition and adherence to medication
in adults with diabetes is important. Identifying predictors to medication
adherence in adults with diabetes would help identify vulnerable patients who are
likely to benefit by improving their adherence levels. METHODS: We conducted a
cross-sectional study at the Dubai Police Health Centre between February 2015 and
November 2015. Questionnaires were used to collect socio-demographic, clinical
and disease related variables and the primary measure of outcome was adherence
levels as measured by the Morisky Medication Adherence Scale (MMAS-8(c)).
Multivariate logistic regression was carried out to identify predictors to
adherence. RESULTS: Four hundred and forty six patients were interviewed. Mean
age 61 year +/- 11. 48.4 % were male. The mean time since diagnosis of diabetes
was 3.2 years (Range 1-15 years). Two hundred and eighty eight (64.6 %) patients
were considered non-adherent (MMAS-8(c) adherence score < 6) while 118 (26.5 %)
had moderate adherence (MMAS-8(c) adherence score 6 = <8) and 40 (9.0 %) high
adherence (MMAS-8(c) adherence scores <8) to their medication respectively. The
strongest predictor for adherence as predicted by the multi-logistic regression
model was the patient's level of education. A technical diploma certificate as
compared to a primary school level of education was the strongest predictor of
adherence (OR = 66.1 CI: 6.93 to 630.43); p < 0.001). The patient's age was also
a predictor of adherence with older patients reporting higher levels of adherence
(OR = 1.113 (CI: 1.045 to 1.185; p = 0.001 for every year increase in age). The
duration of diabetes was also a predictor of adherence (OR = 1.830 (CI: 1.270 to
2.636; p = 0.001 for every year increase in the duration of diabetes). Other
predictors to medication adherence include Insulin use, ethnicity and certain
cultural behaviours. CONCLUSION: A number of important predictors to medication
adherence in diabetics were identified in this study. Such predictors could help
develop policies for improving adherence in diabetics.
PMID- 27512653
TI - Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its
Severity?
AB - OBJECTIVES: Traditionally, the urinary tract has been thought to be sterile in
the absence of a clinically identifiable infection. However, recent evidence
suggests that the urinary tract harbors a variety of bacterial species, known
collectively as the urinary microbiome, even when clinical cultures are negative.
Whether these bacteria promote urinary health or contribute to urinary tract
disease remains unknown. Emerging evidence indicates that a shift in the urinary
microbiome may play an important role in urgency urinary incontinence (UUI). The
goal of this prospective pilot study was to determine how the urinary microbiome
is different between women with and without UUI. We also sought to identify if
characteristics of the urinary microbiome are associated with UUI severity.
METHODS: We collected urine from clinically well-characterized women with UUI (n
= 10) and normal bladder function (n = 10) using a transurethral catheter to
avoid bacterial contamination from external tissue. To characterize the resident
microbial community, we amplified the bacterial 16S rRNA gene by PCR and
performed sequencing using Illumina MiSeq. Sequences were processed using the
workflow package QIIME. We identified bacteria that had differential relative
abundance between UUI and controls using DESeq2 to fit generalized linear models
based on the negative binomial distribution. We also identified relationships
between the diversity of the urinary microbiome and severity of UUI symptoms with
Pearson's correlation coefficient. RESULTS: We successfully extracted and
sequenced bacterial DNA from 95% of the urine samples and identified that there
is a polymicrobial community in the female bladder in both healthy controls and
women with UUI. We found the relative abundance of 14 bacteria significantly
differed between control and UUI samples. Furthermore, we established that an
increase in UUI symptom severity is associated with a decrease in microbial
diversity in women with UUI. CONCLUSIONS: Our study provides further
characterization of the urinary microbiome in both healthy controls and
extensively phenotyped women with UUI. Our results also suggest that the urinary
microbiome may play an important role in the pathophysiology of UUI and that the
loss of microbial diversity may be associated with clinical severity.
PMID- 27512655
TI - Oncolytic virotherapy: the questions and the promise.
AB - Oncolytic virotherapy is a new strategy to reduce tumor burden through selective
virus replication in rapidly proliferating cells. Oncolytic viruses are members
of at least ten virus families, each with its advantages and disadvantages. Here,
I briefly review the recent advances and key challenges, as exemplified by the
best-studied platforms. Recent advances include preclinical proof of feasibility,
clinical evidence of tolerability and effectiveness, and the development of new
strategies to improve efficacy. These include engineered tumor selectivity and
expression of antitumorigenic genes that could function independently of virus
replication, identification of combinatorial therapies that accelerate
intratumoral virus propagation, and modification of immune responses and vascular
delivery for treatment of metastatic disease. Key challenges are to select
"winners" from the distinct oncolytic platforms that can stimulate anti-cancer
immunity without affecting virus replication and can lyse cancer stem cells,
which are most likely responsible for tumor maintenance, aggressiveness, and
recurrence. Preventing the emergence of resistant tumor cells during virotherapy
through the activation of multiple death pathways, the development of a better
understanding of the mechanisms of cancer stem-cell lysis, and the development of
more meaningful preclinical animal models are additional challenges for the next
generation of engineered viruses.
PMID- 27512656
TI - Oncolytic virus therapy for cancer.
AB - The use of oncolytic viruses to treat cancer is based on the selection of tropic
tumor viruses or the generation of replication selective vectors that can either
directly kill infected tumor cells or increase their susceptibility to cell death
and apoptosis through additional exposure to radiation or chemotherapy. In
addition, viral vectors can be modified to promote more potent tumor cell death,
improve the toxicity profile, and/or generate host antitumor immunity. A variety
of viruses have been developed as oncolytic therapeutics, including adenovirus,
vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and
reovirus. The clinical development of oncolytic viral therapy has accelerated in
the last few years, with several vectors entering clinical trials for a variety
of cancers. In this review, current strategies to optimize the therapeutic
effectiveness and safety of the major oncolytic viruses are discussed, and a
summary of current clinical trials is provided. Further investigation is needed
to characterize better the clinical impact of oncolytic viruses, but there are
increasing data demonstrating the potential promise of this approach for the
treatment of human and animal cancers.
PMID- 27512657
TI - Cell carriers for oncolytic viruses: current challenges and future directions.
AB - The optimal route for clinical delivery of oncolytic viruses is thought to be
systemic intravenous injection; however, the immune system is armed with several
highly efficient mechanisms to remove pathogens from the circulatory system. To
overcome the challenges faced in trying to delivery oncolytic viruses
specifically to tumors via the bloodstream, carrier cells have been investigated
to determine their suitability as delivery vehicles for systemic administration
of oncolytic viruses. Cell carriers protect viruses from neutralization, one of
the most limiting aspects of oncolytic virus interaction with the immune system.
Cell carriers can also possess inherent tumor tropism, thus directing the
delivery of the virus more specifically to a tumor. With preclinical studies
already demonstrating the success and feasibility of this approach with multiple
oncolytic viruses, clinical evaluation of cell-mediated delivery of viruses is on
the horizon. Meanwhile, ongoing preclinical studies are aimed at identifying new
cellular vehicles for oncolytic viruses and improving current promising cell
carrier platforms.
PMID- 27512658
TI - Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs.
AB - Oncolytic viruses are emerging as a potential new way of treating cancers. They
are selectively replication-competent viruses that propagate only in actively
dividing tumor cells but not in normal cells and, as a result, destroy the tumor
cells by consequence of lytic infection. At least six different oncolytic herpes
simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and
they have demonstrated an excellent safety profile and intimations of efficacy.
The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec
[OncoVex(GM-CSF)]), is almost complete, with extremely positive early results
reported. Intuitively, therapeutically beneficial interactions between oHSV and
chemotherapeutic and targeted therapeutic drugs would be limited as the virus
requires actively dividing cells for maximum replication efficiency and most
anticancer agents are cytotoxic or cytostatic. However, combinations of such
agents display a range of responses, with antagonistic, additive, or, perhaps
most surprisingly, synergistic enhancement of antitumor activity. When
synergistic interactions in cancer cell killing are observed, chemotherapy dose
reductions that achieve the same overall efficacy may be possible, resulting in a
valuable reduction of adverse side effects. Therefore, the combination of an oHSV
with "standard-of-care" drugs makes a logical and reasonable approach to improved
therapy, and the addition of a targeted oncolytic therapy with "standard-of-care"
drugs merits further investigation, both preclinically and in the clinic.
Numerous publications report such studies of oncolytic HSV in combination with
other drugs, and we review their findings here. Viral interactions with cellular
hosts are complex and frequently involve intracellular signaling networks, thus
creating diverse opportunities for synergistic or additive combinations with many
anticancer drugs. We discuss potential mechanisms that may lead to synergistic
interactions.
PMID- 27512659
TI - Arming viruses in multi-mechanistic oncolytic viral therapy: current research and
future developments, with emphasis on poxviruses.
AB - The field of oncolytic virology has made great strides in recent years. However,
one key finding has been that the use of viral agents that replicate selectively
in tumors is usually insufficient to achieve anything beyond small and transient
responses. Instead, like most cancer therapies, oncolytic viruses are most
effective in combination with other therapies, which is where they have proven
therapeutic effects in clinical and preclinical studies. In cases of some of the
smaller RNA viruses, effects can only be achieved through combination regimens
with chemotherapy, radiotherapy, or targeted conventional therapies. However,
larger DNA viruses are able to express one or more transgenes; thus, therapeutic
mechanisms can be built into the viral vector itself. The incorporated approaches
into arming oncolytic viruses through transgene expression will be the main focus
of this review, including use of immune activators, prodrug converting enzymes,
anti-angiogenic factors, and targeting of the stroma. This will focus on
poxviruses as model systems with large cloning capacities, which have routinely
been used as transgene expression vectors in different settings, including
vaccine and oncolytic viral therapy.
PMID- 27512660
TI - Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage
colony stimulating factor for the treatment of malignant melanoma.
AB - Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal
cells are a new area of therapeutic development in oncology. An attenuated
herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM
CSF), known as talimogene laherparepvec (T-VEC), has been identified as an
attractive oncolytic virus for cancer therapy based on preclinical tumor studies
and results from early-phase clinical trials and a large randomized Phase III
study in melanoma. In this review, we discuss the basic biology of T-VEC,
describe the role of GM-CSF as an immune adjuvant, summarize the preclinical
data, and report the outcomes of published clinical trials using T-VEC. The
emerging data suggest that T-VEC is a safe and potentially effective antitumor
therapy in malignant melanoma and represents the first oncolytic virus to
demonstrate therapeutic activity against human cancer in a randomized, controlled
Phase III study.
PMID- 27512661
TI - Oncolytic viral therapy for pancreatic cancer: current research and future
directions.
AB - The development of targeted agents and chemotherapies for pancreatic cancer has
only modestly affected clinical outcome and not changed 5-year survival.
Fortunately the genetic and molecular mechanisms underlying pancreatic cancer are
being rapidly uncovered and are providing opportunities for novel targeted
therapies. Oncolytic viral therapy is one of the most promising targeted agents
for pancreatic cancer. This review will look at the current state of the
development of these self-replicating nanoparticles in the treatment of
pancreatic cancer.
PMID- 27512662
TI - Applications of coxsackievirus A21 in oncology.
AB - The clinical management of cancer continues to be dominated by macroscopic
surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing
oncology is to achieve more selective, less toxic and effective methods of
targeting disseminated tumors, a challenge oncolytic virotherapy may be well
placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based
mechanism of virus internalization and lysis in the last decade has suggested
promise for CVA21 as a virotherapy against malignancies which overexpress those
receptors. Preclinical studies have demonstrated proof of principle, and with the
results of early clinical trials awaited, CVA21 may be one of the few viruses to
demonstrate benefit for patients. This review outlines the potential of CVA21 as
an oncolytic agent, describing the therapeutic development of CVA21 in
preclinical studies and early stage clinical trials. Preclinical evidence
supports the potential use of CVA21 across a range of malignancies. Malignant
melanoma is the most intensively studied cancer, and may represent a "test case"
for future development of the virus. Although there are theoretical barriers to
the clinical utility of oncolytic viruses like CVA21, whether these will block
the efficacy of the virus in clinical practice remains to be established, and is
a question which can only be answered by appropriate trials. As these data become
available, the rapid journey of CVA21 from animal studies to clinical trials may
offer a model for the translation of other oncolytic virotherapies from
laboratory to clinic.
PMID- 27512663
TI - Live attenuated measles virus vaccine therapy for locally established malignant
glioblastoma tumor cells.
AB - Glioblastoma multiforme is the most aggressive malignant primary brain tumor in
humans, with poor prognosis. A new glioblastoma cell line (ANGM5) was established
from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent
surgery for an intracranial tumor. This study was carried out to evaluate the
antitumor effect of live attenuated measles virus (MV) Schwarz vaccine strain on
glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz
strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma
multiform (ANGM5) cell lines. The infected confluent monolayer appeared to be
covered with syncytia with granulation and vacuolation, as well as cell rounding,
shrinkage, and large empty space with cell debris as a result of cell lysis and
death. Cell lines infected with virus have the ability for hemadsorption to human
red blood cells after 72 hours of infection, whereas no hemadsorption of
uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal
antibodies in infected cells of all cell lines by immunocytochemistry assay gave
positive results (brown color) in the cytoplasm of infected cells. Cell viability
was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl)-2,5
diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect
for MV (P<=0.05) on growth of ANGM5 and rhabdomyosarcoma cell lines after 72
hours of infection. Induction of apoptosis by MV was assessed by measuring
mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of
infection. Apoptotic cells were counted, and the mean percentage of dead cells
was significantly higher after 48, 72, and 120 hours of infection compared with
control cells. This study concludes that live attenuated MV Schwarz vaccine
induces the oncolytic effect in Iraqi tumor cell line ANGM5 and in the
rhabdomyosarcoma cell line through syncytia in tumor cells, which is one of the
causes of cell death. The MV vaccine strain has the ability to insert its
hemagglutinin protein into the tumor cell surface, leading to modification of the
antigenic surface of tumor cells that may induce an antitumor immune response, MV
vaccine strain induced cell killing by direct cytolysis and apoptosis induction.
These antitumor features may indicate the use of MV in the treatment of
glioblastoma.
PMID- 27512664
TI - Reovirus in cancer therapy: an evidence-based review.
AB - Reovirus, a double-stranded ribonucleic acid virus and benign human pathogen,
preferentially infects and kills cancer cells in its unmodified form, and is one
of the leading oncolytic viruses currently undergoing clinical trials
internationally. With 32 clinical trials completed or ongoing thus far, reovirus
has demonstrated clinical therapeutic applicability against a multitude of
cancers, including but not limited to breast cancer, prostate cancer, pancreatic
cancer, malignant gliomas, advanced head and neck cancers, and metastatic ovarian
cancers. Phase I trials have demonstrated that reovirus is safe to use via both
intralesional/intratumoral and systemic routes of administration, with the most
common adverse reactions being grade I/II toxicities, such as flu-like illness
(fatigue, nausea, vomiting, headache, fever/chills, dizziness), diarrhea, and
lymphopenia. In subsequent Phase II trials, reovirus administration was
demonstrated to successfully decrease tumor size and promote tumor necrosis,
thereby complementing compelling preclinical evidence of tumor destruction by the
virus. Importantly, reovirus has been shown to be effective as a monotherapy, as
well as in combination with other anticancer options, including radiation and
chemotherapeutic agents, such as gemcitabine, docetaxel, paclitaxel, and
carboplatin. Of note, the first Phase III clinical trial using reovirus in
combination with paclitaxel and carboplatin for the treatment of head and neck
cancers is under way. Based on the evidence from clinical trials, we
comprehensively review the use of reovirus as an anticancer agent, acknowledge
key obstacles, and suggest future directions to ultimately potentiate the
efficacy of reovirus oncotherapy.
PMID- 27512665
TI - Myxoma virus attenuates expression of activating transcription factor 4 (ATF4)
which has implications for the treatment of proteasome inhibitor-resistant
multiple myeloma.
AB - The recent development of chemotherapeutic proteasome inhibitors, such as
bortezomib, has improved the outcomes of patients suffering from the plasma cell
malignancy multiple myeloma. Unfortunately, many patients treated with these
drugs still suffer relapsing disease due to treatment-induced upregulation of the
antiapoptotic protein Mcl1. We have recently demonstrated that an oncolytic
poxvirus, known as myxoma, can rapidly eliminate primary myeloma cells by
inducing cellular apoptosis. The efficacy of myxoma treatment on proteasome
inhibitor-relapsed or -refractory myeloma, however, remains unknown. We now
demonstrate that myxoma-based elimination of myeloma is not affected by cellular
resistance to proteasome inhibitors. Additionally, myxoma virus infection
specifically prevents expression of Mcl1 following induction of the unfolded
protein response, by blocking translation of the unfolded protein response
activating transcription factor (ATF)4. These results suggest that myxoma-based
oncolytic therapy represents an attractive option for myeloma patients whose
disease is refractory to chemotherapeutic proteasome inhibitors due to
upregulation of Mcl1.
PMID- 27512667
TI - The emerging therapeutic potential of the oncolytic immunotherapeutic Pexa-Vec
(JX-594).
AB - Oncolytic immunotherapeutics (OIs) are viruses designed to preferentially
replicate in and lyse cancer cells, thereby triggering antitumor immunity.
Numerous oncolytic platforms are currently in clinical development. Here we
review preclinical and clinical experience with Pexa-Vec (pexastimogene
devacirepvec, JX-594). Pexa-Vec is derived from a vaccinia vaccine strain that
has been engineered to target cancer cells and express the therapeutic transgene
granulocyte macrophage colony-stimulating factor (GM-CSF) in order to stimulate
antitumor immunity. Key to its ability to target metastatic disease is the
evolution of unique vaccinia virus characteristics that allow for effective
systemic dissemination. Multiple mechanisms of action (MOA) for Pexa-Vec have
been demonstrated in preclinical models and patients: 1) tumor cell infection and
lysis, 2) antitumor immune response induction, and 3) tumor vascular disruption.
This review will summarize data on the Pexa-Vec MOA as well as provide an
overview of the Pexa-Vec clinical development program from multiple Phase I
studies, Phase II studies in renal cell cancer and colorectal cancer, through
Phase IIb clinical testing in patients with advanced hepatocellular carcinoma
(primary liver cancer).
PMID- 27512666
TI - The ex vivo purge of cancer cells using oncolytic viruses: recent advances and
clinical implications.
AB - Hematological malignancies are treated with intensive high-dose chemotherapy,
with or without radiation. This is followed by hematopoietic stem cell (HSC)
transplantation (HSCT) to rescue or reconstitute hematopoiesis damaged by the
anticancer therapy. Autologous HSC grafts may contain cancer cells and purging
could further improve treatment outcomes. Similarly, allogeneic HSCT may be
improved by selectively purging alloreactive effector cells from the graft rather
than wholesale immune cell depletion. Viral agents that selectively replicate in
specific cell populations are being studied in experimental models of cancer and
immunological diseases and have potential applications in the context of HSC
graft engineering. This review describes preclinical studies involving oncolytic
virus strains of adenovirus, herpes simplex virus type 1, myxoma virus, and
reovirus as ex vivo purging agents for HSC grafts, as well as in vitro and in
vivo experimental studies using oncolytic coxsackievirus, measles virus,
parvovirus, vaccinia virus, and vesicular stomatitis virus to eradicate
hematopoietic malignancies. Alternative ex vivo oncolytic virus strategies are
also outlined that aim to reduce the risk of relapse following autologous HSCT
and mitigate morbidity and mortality due to graft-versus-host disease in
allogeneic HSCT.
PMID- 27512668
TI - Extended disease-free interval of 6 years in a recurrent glioblastoma multiforme
patient treated with G207 oncolytic viral therapy.
AB - BACKGROUND: Glioblastoma multiforme (GBM) is a relentless primary central nervous
system malignancy that remains resistant to conventional therapy despite major
advances in clinical neurooncology. This report details the case of a patient who
had failed conventional treatment for recurrent GBM and was ultimately treated
with a genetically engineered herpes simplex virus (HSV) type 1 vector, G207.
METHODS: Case report detailing the outcomes of one patient enrolled into the gene
therapy arm of the Neurovir G207 protocol whereby stereotactic injection of 120
uL G207 viral suspension containing 1*10(7) plaque-forming units (or active viral
particles) was made into the enhancing region of the tumor. RESULTS: In this
patient, despite aggressive surgical resection, adjuvant radiotherapy and
chemotherapy, tumor progression occurred. However, with G207 oncolytic therapy
and brief exposures to second and third treatments, this patient had an extended
survival time of 7.5 years and a 6-year apparent disease-free interval, an
extraordinarily unusual finding in the pretemozolomide era. CONCLUSION: With
minimal adjunctive chemotherapy, including one course of temozolomide, one course
of procarbazine, and four cycles of irinotecan, the patient survived over 7 years
before the next recurrence. Addition of G207 to this patient's traditional
therapy may have been the critical treatment producing her prolonged survival.
This report demonstrates the potential for long-term response to a one-time
treatment with oncolytic HSV and encourages continued research on oncolytic viral
therapy for GBM.
PMID- 27512669
TI - Chemovirotherapy: combining chemotherapeutic treatment with oncolytic
virotherapy.
AB - Oncolytic virotherapy has made significant progress in recent years, however,
widespread approval of virotherapeutics is still limited. Primarily, this is due
to the fact that currently available virotherapeutics are mostly tested in
monotherapeutic clinical trials exclusively (ie, not in combination with other
therapies) and so far have achieved only small and often clinically insignificant
responses. Given that the predominantly immunotherapeutic mechanism of
virotherapeutics is somewhat time-dependent and rapidly growing tumors therefore
exhibit only minor chances of being captured in time, scenarios with combination
partners are postulated to be more effective. Combinatory settings would help to
achieve a rapid stabilization or even reduction of onset tumor masses while
providing enough time (numerous months) for achieving immuno(viro)therapeutic
success. For this reason, combination strategies of virotherapy with highly
genotoxic regimens, such as chemotherapy, are of major interest. A number of
clinical trials bringing the concepts of chemotherapy and virotherapy together
have previously been undertaken, but optimal scheduling of chemovirotherapy
(maximizing the anti-tumor effect while minimizing the risk of overlapping
toxicity) still constitutes a major challenge. Therefore, an overview of
published as well as ongoing Phase I-III trials should improve our understanding
of current challenges and future developments in this field.
PMID- 27512670
TI - Therapeutic potential of oncolytic Newcastle disease virus: a critical review.
AB - Newcastle disease virus (NDV) features a natural preference for replication in
many tumor cells compared with normal cells. The observed antitumor effect of NDV
appears to be a result of both selective killing of tumor cells and induction of
immune responses. Genetic manipulations to change viral tropism and arming the
virus with genes encoding for cytokines improved the oncolytic capacity of NDV.
Several intracellular proteins in tumor cells, including antiapoptotic proteins
(Livin) and oncogenic proteins (H-Ras), are relevant for the oncolytic activity
of NDV. Defects in the interferon system, found in some tumor cells, also
contribute to the oncolytic selectivity of NDV. Notwithstanding, NDV displays
effective oncolytic activity in many tumor types, despite having intact
interferon signaling. Taken together, several cellular systems appear to dictate
the selective oncolytic activity of NDV. Some barriers, such as neutralizing
antibodies elicited during NDV treatment and the extracellular matrix in tumor
tissue appear to interfere with spread of NDV and reduce oncolysis. To further
understand the oncolytic activity of NDV, we compared two NDV strains, ie, an
attenuated virus (NDV-HUJ) and a pathogenic virus (NDV-MTH-68/H). Significant
differences in amino acid sequence were noted in several viral proteins,
including the fusion precursor (F0) glycoprotein, an important determinant of
replication and pathogenicity. However, no difference in the oncolytic activity
of the two strains was noted using human tumor tissues maintained as organ
cultures or in mouse tumor models. To optimize virotherapy in clinical trials, we
describe here a unique organ culture methodology, using a biopsy taken from a
patient's tumor before treatment for ex vivo infection with NDV to determine the
oncolytic potential on an individual basis. In conclusion, oncolytic NDV is an
excellent candidate for cancer therapy, but more knowledge is needed to ensure
success in clinical trials.
PMID- 27512671
TI - Promising oncolytic agents for metastatic breast cancer treatment.
AB - New therapies for metastatic breast cancer patients are urgently needed. The long
term survival rates remain unacceptably low for patients with recurrent disease
or disseminated metastases. In addition, existing therapies often cause a variety
of debilitating side effects that severely impact quality of life. Oncolytic
viruses constitute a developing therapeutic modality in which interest continues
to build due to their ability to spare normal tissue while selectively destroying
tumor cells. A number of different viruses have been used to develop oncolytic
agents for breast cancer, including herpes simplex virus, adenovirus, vaccinia
virus, measles virus, reovirus, and others. In general, clinical trials for
several cancers have demonstrated excellent safety records and evidence of
efficacy. However, the impressive tumor responses often observed in preclinical
studies have yet to be realized in the clinic. In order for the promise of
oncolytic virotherapy to be fully realized for breast cancer patients,
effectiveness must be demonstrated in metastatic disease. This review provides a
summary of oncolytic virotherapy strategies being developed to target metastatic
breast cancer.
PMID- 27512672
TI - Novel therapeutic strategies in human malignancy: combining immunotherapy and
oncolytic virotherapy.
AB - Results from randomized clinical trials over the last several years have finally
begun to demonstrate the potential of oncolytic viral therapies to treat a
variety of cancers. One reason for these successes has been the realization that
this platform is most effective when considered primarily as an immunotherapy.
Cancer immunotherapy has also made dramatic strides recently with antibodies
capable of blocking immune checkpoint inhibitors and adoptive T-cell therapies,
notably CAR T-cells, leading a panel of novel and highly clinically effective
therapies. It is clear therefore that an understanding of how and when these
complementary approaches can most effectively be combined offers the real hope of
moving beyond simply treating the disease and toward starting to talk about
curative therapies. In this review we discuss approaches to combining these
therapeutic platforms, both through engineering the viral vectors to more
beneficially interact with the host immune response during therapy, as well as
through the direct combinations of different therapeutics. This primarily, but
not exclusively focuses on strains of oncolytic vaccinia virus. Some of the
results reported to date, primarily in pre-clinical models but also in early
clinical trials, are dramatic and hold great promise for the future development
of similar therapies and their translation into cancer therapies.
PMID- 27512673
TI - Oncolytic virotherapy for head and neck cancer: current research and future
developments.
AB - Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Despite
recent advancements in surgical, chemotherapy, and radiation treatments, HNC
remains a highly morbid and fatal disease. Unlike many other cancers, local
control rather than systemic control is important for HNC survival. Therefore,
novel local therapy in addition to systemic therapy is urgently needed. Oncolytic
virotherapy holds promise in this regard as viruses can be injected
intratumorally as well as intravenously with excellent safety profiles. This
review will discuss the recent advancements in oncolytic virotherapy,
highlighting some of the most promising candidates and modifications to date.
PMID- 27512674
TI - On the potential of oncolytic virotherapy for the treatment of canine cancers.
AB - Over 6 million dogs are diagnosed with cancer in the USA each year. Treatment
options for many of these patients are limited. It is important that the
veterinary and scientific communities begin to explore novel treatment protocols
for dogs with cancer. Oncolytic viral therapy is a promising treatment option
that may prove to be relatively inexpensive and effective against several types
of cancer. The efficacy of oncolytic virus therapies has been clearly
demonstrated in murine cancer models, but the positive outcomes observed in mice
are not always seen in human cancer patients. These therapies should be
thoroughly evaluated in dogs with spontaneously arising cancers to provide needed
information about the potential effectiveness of virus treatment for human
cancers and to promote the health of our companion animals. This article provides
a review of the results of oncolytic virus treatment of canine cancers.
PMID- 27512675
TI - Advances in the design and development of oncolytic measles viruses.
AB - A successful oncolytic virus is one that selectively propagates and destroys
cancerous tissue without causing excessive damage to the normal surrounding
tissue. Oncolytic measles virus (MV) is one such virus that exhibits this
characteristic and thus has rapidly emerged as a potentially useful anticancer
modality. Derivatives of the Edmonston MV vaccine strain possess a remarkable
safety record in humans. Promising results in preclinical animal models and
evidence of biological activity in early phase trials contribute to the
enthusiasm. Genetic modifications have enabled MV to evolve from a vaccine agent
to a potential anticancer therapy. Specifically, alterations of the MV genome
have led to improved tumor selectivity and delivery, therapeutic potency, and
immune system modulation. In this article, we will review the advancements that
have been made in the design and development of MV that have led to its use as a
cancer therapy. In addition, we will discuss the evidence supporting its use, as
well as the challenges associated with MV as a potential cancer therapeutic.
PMID- 27512676
TI - Oncolytic virotherapy for human malignant mesothelioma: recent advances.
AB - Cancer virotherapy is an attractive alternative to conventional treatments
because it offers a wide range of antitumor effects due to 1) the diversity of
the oncolytic viruses that are now available and 2) their multifaceted activities
against both tumor cells and tumor vessels, in addition to their ability to
induce antitumor immune responses. In this review, we summarize preclinical and
clinical data regarding the targeting of malignant mesothelioma (MM) by oncolytic
viruses. We also discuss the potential of other oncolytic viruses that have
already shown antitumor effects against several malignancies in advanced clinical
trials but are yet to be tested against MM cells. Finally, we review how the
activation of the immune system and combinations with other types of anticancer
treatments could support the development of oncolytic virotherapy for the
treatment of MM.
PMID- 27512677
TI - Oncolytic Sendai virus-based virotherapy for cancer: recent advances.
AB - Many drugs have been developed and optimized for the treatment of cancer;
however, it is difficult to completely cure cancer with anticancer drugs alone.
Therefore, the development of new therapeutic technologies, in addition to new
anticancer drugs, is necessary for more effective oncotherapy. Oncolytic viruses
are one potential new anticancer strategy. Various oncolytic viruses have been
developed for safe and effective oncotherapy. Recently, Sendai virus-based
oncotherapy has been reported by several groups, and attention has been drawn to
its unique anticancer mechanisms, which are different from those of the
conventional oncolytic viruses that kill cancer cells by cancer cell-selective
replication. Here, we introduce Sendai virus-based virotherapy and its anticancer
mechanisms.
PMID- 27512678
TI - Patient-derived mesenchymal stem cells as delivery vehicles for oncolytic
virotherapy: novel state-of-the-art technology.
AB - Oncolytic virotherapy is gaining interest in the clinic as a new weapon against
cancer. In vivo administration of oncolytic viruses showed important limitations
that decrease their effectiveness very significantly: the antiviral immune
response causes the elimination of the therapeutic effect, and the poor natural
ability of oncolytic viruses to infect micrometastatic lesions significantly
minimizes the effective dose of virus. This review will focus on updating the
technical and scientific foundations of one of the strategies developed to
overcome these limitations, ie, using cells as vehicles for oncolytic viruses.
Among many candidates, a special type of adult stem cell, mesenchymal stem cells
(MSCs), have already been used in the clinic as cell vehicles for oncolytic
viruses, partly due to the fact that these cells are actively being evaluated for
other indications. MSC carrier cells are used as Trojan horses loaded with
oncoviruses, are administered systemically, and release their cargos at the right
places. MSCs are equipped with an array of molecules involved in cell arrest in
the capillaries (integrins and selectins), migration toward specific parenchymal
locations within tissues (chemokine receptors), and invasion and degradation of
the extracellular matrix (proteases). In addition to anatomical targeting
capacity, MSCs have a well-recognized role in modulating immune responses by
affecting cells of the innate (antigen-presenting cells, natural killer cells)
and adaptive immune system (effector and regulatory lymphocytes). Therefore,
carrier MSCs may also modulate the immune responses taking place after therapy,
ie, the antiviral and the antitumor immune responses.
PMID- 27512679
TI - Mechanistic insights into the oncolytic activity of vesicular stomatitis virus in
cancer immunotherapy.
AB - Immunotherapy and oncolytic virotherapy have both shown anticancer efficacy in
the clinic as monotherapies but the greatest promise lies in therapies that
combine these approaches. Vesicular stomatitis virus is a prominent oncolytic
virus with several features that promise synergy between oncolytic virotherapy
and immunotherapy. This review will address the cytotoxicity of vesicular
stomatitis virus in transformed cells and what this means for antitumor immunity
and the virus' immunogenicity, as well as how it facilitates the breaking of
tolerance within the tumor, and finally, we will outline how these features can
be incorporated into the rational design of new treatment strategies in
combination with immunotherapy.
PMID- 27512680
TI - Targeting tumor vasculature through oncolytic virotherapy: recent advances.
AB - The oncolytic virotherapy field has made significant advances in the last decade,
with a rapidly increasing number of early- and late-stage clinical trials, some
of them showing safety and promising therapeutic efficacy. Targeting tumor
vasculature by oncolytic viruses (OVs) is an attractive strategy that offers
several advantages over nontargeted viruses, including improved tumor viral
entry, direct antivascular effects, and enhanced antitumor efficacy. Current
understanding of the biological mechanisms of tumor neovascularization, novel
vascular targets, and mechanisms of resistance has allowed the development of
oncolytic viral vectors designed to target tumor neovessels. While some OVs (such
as vaccinia and vesicular stomatitis virus) can intrinsically target tumor
vasculature and induce vascular disruption, the majority of reported vascular
targeted viruses are the result of genetic manipulation of their viral genomes.
Such strategies include transcriptional or transductional endothelial targeting,
"armed" viruses able to downregulate angiogenic factors, or to express
antiangiogenic molecules. The above strategies have shown preclinical safety and
improved antitumor efficacy, either alone, or in combination with standard or
targeted agents. This review focuses on the recent efforts toward the development
of vascular-targeted OVs for cancer treatment and provides a
translational/clinical perspective into the future development of new generation
biological agents for human cancers.
PMID- 27512681
TI - Combining HDAC inhibitors with oncolytic virotherapy for cancer therapy.
AB - Histone deacetylase (HDAC) enzymes play a critical role in the epigenetic
regulation of cellular functions and signaling pathways in many cancers. HDAC
inhibitors (HDACi) have been validated for single use or in combination with
other drugs in oncologic therapeutics. An even more novel combination therapy
with HDACi is to use them with an oncolytic virus. HDACi may lead to an
amplification of tumor-specific lytic effects by facilitating increased cycles of
viral replication, but there may also be direct anticancer effects of the drug by
itself. Here, we review the molecular mechanisms of anti-cancer effects of the
combination of oncolytic viruses with HDACi.
PMID- 27512682
TI - Ultrasound-mediated oncolytic virus delivery and uptake for increased therapeutic
efficacy: state of art.
AB - The field of ultrasound (US) has changed significantly from medical imaging and
diagnosis to treatment strategies. US contrast agents or microbubbles (MB) are
currently being used as potential carriers for chemodrugs, small molecules,
nucleic acids, small interfering ribonucleic acid, proteins, adenoviruses, and
oncolytic viruses. Oncolytic viruses can selectively replicate within and destroy
a cancer cell, thus making them a powerful therapeutic in treating late-stage or
metastatic cancer. These viruses have been shown to have robust activity in
clinical trials when injected directly into tumor nodules. However limitations in
oncolytic virus' effectiveness and its delivery approach have warranted
exploration of ultrasound-mediated delivery. Gene therapy bearing adenoviruses or
oncolytic viruses can be coupled with MBs and injected intravenously. Following
application of US energy to the target region, the MBs cavitate, and the
resulting shock wave enhances drug, gene, or adenovirus uptake. Though the
underlying mechanism is yet to be fully understood, there is evidence to suggest
that mechanical pore formation of cellular membranes allows for the temporary
uptake of drugs. This delivery method circumvents the limitations due to
stimulation of the immune system that prevented intravenous administration of
viruses. This review provides insight into this intriguing new frontier on the
delivery of oncolytic viruses to tumor sites.
PMID- 27512684
TI - The effects of conjugated linoleic acids on breast cancer: A systematic review.
AB - Recently prevention strategies for breast cancer are focused on lifestyle
modification such as diet. Some dietary factors such as Conjugated linoleic acid
(CLA) can lower the risk of breast cancer, metastasis and some factors concerning
this malignancy. Many studies have been established in this field, but their
results are inconsistent. Therefore, we evaluated this association based on
systematic review among published scientific literature. We performed an
electronic search using PubMed, Cochrane, Scopus, Google Scholar and Persian
database (Iran Medex, magiran) to identify relevant studies. We summarized the
findings of 8 papers in this review. Although, three cohort studies were not
overall identified a protective effect of CLA dietary intake or CLA content in
breast tissue on breast cancer incidence, metastasis and death, one of them
showed an inverse association after adjusting for age. Also, among case-control
studies a weak inverse association between breast cancer risk and CLA dietary
intake and serum levels among post-menopausal women was reported. Besides, a
clinical trial showed that some indicator of breast tumor decreased after CLA
administration among women with breast adenocarcinoma. Lacking published evidence
suggested inconsistent results. So, further well-designed studies are required,
particularly in considering the main breast cancer risk factors.
PMID- 27512683
TI - Oncolytic virotherapy using herpes simplex virus: how far have we come?
AB - Oncolytic virotherapy exploits the properties of human viruses to naturally
cytolysis of cancer cells. The human pathogen herpes simplex virus (HSV) has
proven particularly amenable for use in oncolytic virotherapy. The relative
safety of HSV coupled with extensive knowledge on how HSV interacts with the host
has provided a platform for manipulating HSV to enhance the targeting and killing
of human cancer cells. This has culminated in the approval of talimogene
laherparepvec for the treatment of melanoma. This review focuses on the
development of HSV as an oncolytic virus and where the field is likely to head in
the future.
PMID- 27512685
TI - The effect of Prosopis farcta beans extract on blood biochemical parameters in
streptozotocin-induced diabetic male rats.
AB - BACKGROUND: The use of herbals in the treatment of diabetes mellitus is a well
established practice in traditional medicine. The medicinal plant Prosopis farcta
has some antioxidant activity, which may be useful in diabetic patients. Since,
there is no report on the antidiabetic effect of the P. farcta, this study
evaluated antidiabetic activity of P. farcta bean extract (PFE) in streptozotocin
(STZ)-induced diabetic rats. MATERIALS AND METHODS: Hyperglycemia was induced in
male albino Wistar rats by intraperitoneal injection of STZ (55 mg/kg body weight
[BW]), after which, the animals were randomly allocated into six experimental
groups as follows: Group 1: Normal rats (received normal saline), Groups 2 and 3:
Normal rats received PFE; (50 and 75 mg/kg BW), Group 4: Diabetic control rats,
Group 5: Diabetic rats received PFE (50 mg/kg BW), Group 6: Diabetic rats
received PFE (75 mg/kg BW). Three days after induction of diabetes, rats were
received an extract of PFE orally for 12 days. Blood samples were collected by
cardiac puncture to determine liver enzymes; aspartate aminotransferase and
alanine aminotransferase (AST and ALT), cholesterol, triglyceride (TG), high and
low density lipoproteins (HDL and LDL). RESULTS: The administration of PFE (50
and 75 mg/kg) in STZ-induced diabetic rats significantly reduced the blood
glucose levels when compared with the STZ-control group (227.2 +/- 12.00 and
259.6 +/- 7.03 vs. 454.6 +/- 12.66, P < 0.001). PFE in diabetic groups had no
significant effect on the levels of cholesterol, TG, HDL, LDL, AST, and ALT
compare to the STZ-control group. CONCLUSION: P. farcta could reduce blood
glucose in diabetic rats.
PMID- 27512686
TI - Development of new method and protocol for cryopreservation related to embryo and
oocytes freezing in terms of fertilization rate: A comparative study including
review of literature.
AB - BACKGROUND: Cryopreservation is basically related to meritorious thin samples or
small clumps of cells that are cooled quickly without loss. Our main objective is
to establish and formulate an innovative method and protocol development for
cryopreservation as a gold standard for clinical uses in laboratory practice and
treatment. The knowledge regarding usefulness of cryopreservation in clinical
practice is essential to carry forward the clinical practice and research.
MATERIALS AND METHODS: We are trying to compare different methods of
cryopreservation (in two dozen of cells) at the same time we compare the embryo
and oocyte freezing interms of fertilization rate according to the International
standard protocol. RESULTS: The combination of cryoprotectants and regimes of
rapid cooling and rinsing during warming often allows successful cryopreservation
of biological materials, particularly cell suspensions or thin tissue samples.
Examples include semen, blood, tissue samples like tumors, histological cross
sections, human eggs and human embryos. Although presently many studies have
reported that the children born from frozen embryos or "frosties," show
consistently positive results with no increase in birth defects or development
abnormalities is quite good enough and similar to our study (50-85%).
CONCLUSIONS: We ensure that cryopreservation technology provided useful cell
survivability, tissue and organ preservation in a proper way. Although it varies
according to different laboratory conditions, it is certainly beneficial for
patient's treatment and research. Further studies are needed for standardization
and development of new protocol.
PMID- 27512687
TI - Imaging bacteria with radiolabelled quinolones, cephalosporins and siderophores
for imaging infection: a systematic review.
AB - Bacterial infections are still one of the main causes of patient morbidity and
mortality worldwide. Nowadays, many imaging techniques, like computed tomography
or magnetic resonance imaging, are used to identify inflammatory processes, but,
although they recognize anatomical modifications, they cannot easily distinguish
bacterial infective foci from non bacterial infections. In nuclear medicine, many
efforts have been made to develop specific radiopharmaceuticals to discriminate
infection from sterile inflammation. Several compounds (antimicrobial peptides,
leukocytes, cytokines, antibiotics...) have been radiolabelled and tested in
vitro and in vivo, but none proved to be highly specific for bacteria. Indeed
factors, including the number and strain of bacteria, the infection site, and the
host condition may affect the specificity of tested radiopharmaceuticals.
Ciprofloxacin has been proposed and intensively studied because of its easy
radiolabelling method, broad spectrum, and low cost, but at the same time it
presents some problems such as low stability or the risk of antibiotic
resistance. Therefore, in the present review studies with ciprofloxacin and other
radiolabelled antibiotics as possible substitutes of ciprofloxacin are reported.
Among them we can distinguish different classes, such as cephalosporins,
fluoroquinolones, inhibitors of nucleic acid synthesis, inhibitors of bacterial
cell wall synthesis and inhibitors of protein synthesis; then also others, like
siderophores or maltodextrin-based probes, have been discussed as bacterial
infection imaging agents. A systematic analysis was performed to report the main
characteristics and differences of each antibiotic to provide an overview about
the state of the art of imaging infection with radiolabelled antibiotics.
PMID- 27512688
TI - Preclinical studies and prospective clinical applications for bacteria-targeted
imaging: the future is bright.
AB - Bacterial infections are a frequently occurring and major complication in human
healthcare, in particular due to the rapid increase of antimicrobial resistance
and the emergence of pan-drug-resistant microbes. Current anatomical and
functional imaging modalities are insufficiently capable of distinguishing sites
of bacterial infection from sterile inflammation. Therefore, definitive diagnosis
of an infection can often only be obtained by tissue biopsy and subsequent
culture and, occasionally, a definite diagnosis even appears to be impossible. To
accurately diagnose bacterial infections early, novel imaging modalities are
urgently needed. In this regard, bacteria-targeted imaging is an attractive
option due to its specificity. Here, different bacteria-targeted imaging
approaches are reviewed, and their promising future perspectives are discussed.
PMID- 27512690
TI - Posterior maxillary segmental osteotomy for management of insufficient
intermaxillary vertical space and intermolar width discrepancy: a case report.
AB - BACKGROUNDS: Insufficient intermaxillary space is caused by non-restoration
following tooth extraction in the past, and this involves eruption of the
opposing teeth and changes of the arch structure. Such cases are difficult just
by a simple prosthetic approach, and diversified treatment plans should be
established. Among these, posterior maxillary segmental osteotomy (PMSO) is an
efficient treatment option than extraction of opposing teeth as it surgically
repositions multiple erupted teeth and alveolar bone. PMSO can preserve the
natural teeth; therefore, it is being regarded as a treatment method which can
improve insufficient intermaxillary space significantly. CASE PRESENTATION: In
this case report, the first patient received PMSO in order to place an implant in
the mandibular edentulous space after decreased vertical dimension is restored,
and the second patient received PMSO along with orthodontic treatment to obtain
the intermaxillary space and balance the interarch molar width. CONCLUSION: PMSO
is the treatment of choice when occlusion is compromised in the presence of
decreased vertical dimension or arch length discrepancy.
PMID- 27512689
TI - The role of 90Y-radioembolization in downstaging primary and secondary hepatic
malignancies: a systematic review.
AB - Radioembolization (RE) is an emerging treatment strategy for patients with
primary hepatic malignancies and metastatic liver disease. Though RE is primarily
performed in the palliative setting, a shift toward the curative setting is seen.
Currently, hepatic resection and in selected cases liver transplantation are the
only curative options for patients with a hepatic malignancy. Unfortunately, at
diagnosis most patients are not eligible for liver surgery due to the imbalance
between the necessary liver resection and the remaining liver remnant. However,
in borderline resectable cases, tumor volume reduction and/or increasing the
future liver remnant can lead to a resectable situation. The combination of
selective tumor treatment, the induction of hypertrophy of untreated liver
segments, and its favourable toxicity profile make RE an appealing strategy for
downstaging. The present review discusses the possibilities for RE in the
preoperative setting as a downstaging tool or as a bridge to liver
transplantation.
PMID- 27512691
TI - Obesity in the Otsuka Long Evans Tokushima Fatty Rat: Mechanisms and Discoveries.
AB - Understanding the neural systems underlying the controls of energy balance has
been greatly advanced by identifying the deficits and underlying mechanisms in
rodent obesity models. The current review focuses on the Otsuka Long Evans
Tokushima Fatty (OLETF) rat obesity model. Since its recognition in the 1990s,
significant progress has been made in identifying the causes and consequences of
obesity in this model. Fundamental is a deficit in the cholecystokinin (CCK)-1
receptor gene resulting in the absence of CCK-1 receptors in both the
gastrointestinal track and the brain. OLETF rats have a deficit in their ability
to limit the size of meals and in contrast to CCK-1 receptor knockout mice, do
not compensate for this increase in the size of their spontaneous meals,
resulting in hyperphagia. Prior to becoming obese and in response to pair
feeding, OLETF rats have increased expression of neuropeptide Y (NPY) in the
compact region of the dorsomedial hypothalamus (DMH), and this overexpression
contributes to their overall hyperphagia. Study of the OLETF rats has revealed
important differences in the organization of the DMH in rats and mice and
elucidated previously unappreciated roles for DMH NPY in energy balance and
glucose homeostasis.
PMID- 27512693
TI - The effect of an instructional program based on health belief model in decreasing
cesarean rate among primiparous pregnant mothers.
AB - INTRODUCTION: Although cesarean section has saved many mothers' and infants'
lives, the problem is in its increasing prevalence. According to recent
statistics, the current rate of cesarean in Iran is in fact 3-4 times as more
than the standard rate defined by WHO. Therefore, the present study is aimed to
estimate the effect of an instructional program based on health belief model on
reducing cesarean rate among primiparous pregnant women. MATERIALS AND METHODS:
In this semi-experimental research, 60 primiparous women who had visited Bandar
Abbas Healthcare Centers were selected as the subjects. They were in their 26
30(th) week of pregnancy. They were selected in a multi-stage cluster sampling
method (a combination of clustering and simple randomization), and were divided
into two groups, subjects and control group. The data were gathered using a valid
and reliable questionnaire. The instructional intervention was done after the
completion of the pretest questionnaire based on the sub-constructs of the health
belief model in six instructional sessions. 1 month after the intervention,
posttest questionnaires were completed by the subjects in both groups. The data
were analyzed using descriptive statistics, standard deviation, independent t
test, and paired t-test. The significance level was set at <0.05. RESULTS: Two
groups had a significant difference between awareness score, perceived
sensitivity, intensity, benefits, barriers, self-efficacy, and the performance (P
< 0.001). In the experimental group, nine subjects (30%) had a natural delivery.
CONCLUSION: According to the findings of the current research, an instructional
program illuminated (designed) by the health belief model can significantly
influence pregnant women's awareness, intention, and choice of delivery type.
PMID- 27512692
TI - The Split Second Effect: The Mechanism of How Equinus Can Damage the Human Foot
and Ankle.
AB - We are currently in the process of discovering that many, if not the majority, of
the non-traumatic acquired adult foot and ankle problems are caused by a singular
etiology: non-neuromuscular equinus or the isolated gastrocnemius contracture.
There is no question that this biomechanical association exists and in time much
more will be uncovered. There are three basic questions that must be answered:
why would our calves tighten as we normally age, how does a tight calf, or
equinus, actually cause problems remotely in the foot and ankle, and how do the
forces produced by equinus cause so many seemingly unrelated pathologies in the
foot and ankle? The purpose of this paper is to address the second question: how
does a tight calf mechanically cause problems remotely in the foot and ankle?
There has been little evidence in the literature addressing the biomechanical
mechanisms by which equinus creates damaging forces upon the foot and ankle, and
as a result, a precise, convincing mechanism is still lacking. Thus, the mere
concept that equinus has anything to do with foot pathology is generally unknown
or disregarded. The split second effect, described here, defines exactly how the
silent equinus contracture creates incremental and significant damage and injury
to the human foot and ankle resulting in a wide variety of pathological
conditions. The split second effect is a dissenting theory based on 30 years of
clinical and academic orthopedic foot and ankle experience, keen clinical
observation along the way, and review of the developing literature, culminating
in examination of many hours of slow motion video of normal and abnormal human
gait. To my knowledge, no one has ever described the mechanism in detail this
precise.
PMID- 27512694
TI - Does Islamic spiritual program lead to successful aging? A randomized clinical
trial.
AB - CONTEXT: Successful aging is a pattern of aging that has gained much attention
during recent years. One factor that has a negative impact on successful aging
variables is hypertension. The phenomenon of aging when accompanied with
hypertension promotes spiritual needs. The aim of this study was to examine the
effect of the Islamic spiritual program on successful aging in elderly patients
with hypertension who were referred to health centers of Isfahan, Iran, in 2014.
SETTINGS AND DESIGN: This study was a randomized clinical trial. MATERIALS AND
METHODS: The participants (52 elderly patients with hypertension) were randomly
divided into experimental and control groups. While the control group received
training related to health promotion, the Islamic spiritual program was
implemented in the experimental group for eight sessions in two health centers of
Isfahan. The data collection tools consisted of the 12-item General Health
Questionnaire developed by Goldberg and the satisfaction with life scale
developed by Diener. The questionnaires were completed in three steps; pretest,
posttest, and follow-up (1-month). STATISTICAL ANALYSIS USED: Data were analyzed
using SPSS statistical software version 20 and Chi-square, independent t-test,
and repeated measures ANOVA. RESULTS: Statistical tests showed that the mean
score of general health and life satisfaction of the experiment group had a
meaningful difference from that of the control group in the posttest stage (P <
0.001). This difference was also meaningful in the follow-up stage (P < 0.001).
CONCLUSION: The results of the study indicated the effectiveness of an Islamic
spiritual program on successful aging variables.
PMID- 27512695
TI - Coverage of health-related articles in major local newspapers of Manipur.
AB - BACKGROUND: Newspapers have immense potential for generating health awareness on
diverse issues such as hygiene, immunization, environmental pollution, and
communicable disease. The present study was conducted to determine the frequency
of coverage and types of health-related articles published in local newspapers of
Manipur. MATERIALS AND METHODS: This was a cross-sectional study conducted among
the most regularly published 10 local newspapers (4 English and 6 Manipuri) of
Manipur from February 2011 to January 2012. Health-related articles published in
everyday local newspapers were collected after careful search and finally entered
into a design Proforma under different categories. Data were analyzed using SPSS
version 16. RESULTS: Total health-related articles published were 10,874 and
maximum articles were published during February (12.8%). Maximum health-related
articles were published on Wednesday (16.1%). Among all the health-related
articles, almost half were related with injury followed by public health
articles. Maximum public health and injury-related articles were published on
Monday, but medical topics were published more on Wednesday. Newspapers of both
the languages were publishing public health articles more compared to medical
topics. Public health (72.9%) and injury-related articles (95.9%) were published
maximum in the news items section, but medical topics (45.8%) were published
maximum in the health section of the newspaper. Newspapers of both the languages
published maximum small size articles. CONCLUSIONS: There is a room for
improvement for newspapers of both the languages regarding number of health
related articles' publication, section of publication, and size of the health
articles.
PMID- 27512696
TI - Effect of self-instructional module on knowledge about ebola virus disease among
Nigerian University students in Bengaluru, India.
AB - BACKGROUND: The knowledge about Ebola virus disease (EVD) is very crucial in the
response to the recent outbreak and in order to control its spread. This study
was conducted to assess the effectiveness of self-instructional module (SIM) in
enhancing knowledge of EVD among Nigerian students in Bengaluru, India. MATERIALS
AND METHODS: A pre-experimental study design was employed, and a simple random
sampling technique was used to select 60 participants. A pretest was conducted
with the tool to assess the baseline knowledge of participants after which SIM
was administered to all the participants in two episodes. The posttest was
conducted after 7 days using the same tool to assess any gain in knowledge among
the participants. Data were analyzed using SPSS at an alpha level of 0.001 and
Descriptive analysis (such as percentage, frequency, mean and standard deviation
[SD]) as well as independent t-test was conducted. RESULTS: Findings showed that
the majority of the participants (53%) were males, studying for the undergraduate
degree (85%), 36 participants (60%) were in arts/social courses. More than
average of the participants (67%) had spent only 1-year in India. Majority
(53.3%) had average knowledge but after the administration of the SIM, majority
had very good knowledge about EVD. The mean pretest knowledge score was 16.03
with an SD of 2.951 while the mean posttest knowledge score was 28.22 with SD of
3.273. The calculated t value was 21.432 (P < 0.001). CONCLUSION: SIM was
observed to be very effective in this study and therefore should be adopted by
health personnel in order to convey health-related information to the public.
PMID- 27512697
TI - Effect of anger management education on mental health and aggression of prisoner
women.
AB - BACKGROUND AND PURPOSE: "Uncontrolled anger" threats the compatible and health of
people as serious risk. The effects of weaknesses and shortcomings in the
management of anger, from personal distress and destruction interpersonal
relationships beyond and linked to the public health problems, lack of
compromises, and aggressive behavior adverse outcomes. This study investigates
the effects of anger management education on mental health and aggression of
prisoner women in Isfahan. MATERIALS AND METHODS: The single-group quasi
experimental (pretest, posttest) by prisoner women in the central prison of
Isfahan was done. Multi-stage random sampling method was used. Initially, 165
women were selected randomly and completed the Buss and Perry Aggression
Questionnaire and the General Health Questionnaire-28, and among these, those
with scores >78 (the cut point) in aggression scale was selected and among them
70 were randomly selected. In the next step, interventions in four 90 min
training sessions were conducted. Posttest was performed within 1-month after the
intervention. Data were analyzed using SPSS-20 software. RESULTS: Data analysis
showed that anger management training was effective in reducing aggression (P <
0.001) and also had a positive effect on mental health (P < 0.001). CONCLUSION:
According to the importance of aggression in consistency and individual and
collective health and according to findings, presented educational programs on
anger management is essential for female prisoners.
PMID- 27512698
TI - Effects of a family centered program on perceived social support in patients with
congestive heart failure: An interventional study.
AB - BACKGROUND AND OBJECTIVES: Congestive heart failure is one of the most common
cardiovascular diseases that have a progressive and chronic trend and influences
individuals' and their families' various dimensions. Social support is one of the
psychosocial factors that can have a positive effect on individuals' physical,
mental and social status. Despite the existence of evidences, revealing the
importance of family's support on patients' condition, family centered supportive
interventions with goal of clinical outcomes improvement have been less conducted
among these patients. Therefore, the present study aimed to investigate the
effect of family supportive intervention on the level of the support, received
among heart failure patients. MATERIALS AND METHODS: This is a two-group two
stage clinical trial, conducted on 64 patients with cardiac failure, referring to
selected educational centers and meeting the inclusion criteria, who were
selected through convenient sampling. They were assigned to study (n = 32) and
control (n = 32) groups through random allocation. Data were collected by
questioning through a two-section medical records questionnaire and were analyzed
by SPSS. RESULTS: Results of the study showed that mean scores of received
support score were 13.7 (3.8) in the study and 0.8 (2.4) in the control group.
Independent t-test showed a significant difference in mean changes of perceived
support scores after the intervention between study and control groups (P <
0.001). CONCLUSIONS: Based on familial dimension in social support have a
positive effect on patients' perceived support. Nurses, as professional members
of health care team, and with an important role in education and care of cardiac
failure patients, can support, educate and guide these patients through designing
appropriate care plans and educating their family members.
PMID- 27512699
TI - Experience of Behvarzes (Iranian primary healthcare providers) from giving
primary health services in health houses.
AB - BACKGROUND: Primary healthcare (PHC) providers play a major role in provision of
public health in rural areas in Iran. They are considered as the key elements of
health development in rural population. There is limited research on
clarification of their experiences from provision of health services in their
working conditions. This study aimed to clarify the experience of PHC providers
from working conditions in giving primary health services in health houses
(district branches of rural health care centers). MATERIALS AND METHODS: This is
a content analysis qualitative study, conducted through personal and group
interviews with 12 health workers working in health care centers in rural areas
in Isfahan province, 2010. Sampling continued until data saturation. Data were
analyzed through conventional content analysis and constant comparative method.
RESULTS: Data analysis led to extraction of 11 categories, and finally, four
themes of "ignoring the rights," "causing tension in working climate," "pressure
or overload of expectations beyond the power," and "occupational worn out" were
yielded from the categories. These themes reveal the concepts and nature of PHC
providers' experiences from giving health care at health houses as the first
level of PHC centers. CONCLUSION: The results of the present study showed that
the PHC providers work in a tense condition in health houses. Although they
devote themselves to the health of society members, their own health is
neglected. Policy makers and authorities should amend working conditions of PHC
providers through modification of resources and making supportive and
collaborative strategies to improve the quality of services and promote the
health level of the service receivers.
PMID- 27512700
TI - Effect of physical activity on musculoskeletal discomforts among handicraft
workers.
AB - INTRODUCTION: Handicrafts seems to be one of the high-risk jobs regarding work
related musculoskeletal disorders (WMSDs) which necessitate the implementation of
different corrective intervention like regular physical activities. This study
aimed to investigate the impact of physical activity on WMSDs among craftsmen.
METHODS: This cross-sectional study was an analytical - descriptive study carried
out on 100 craftsmen working in Isfahan, Iran, in 2013. The sampling method was
census, and all workshops involved with this job were included. Information on
demographic parameters and physical activity was collected by demographic forms.
The data related to worker's musculoskeletal discomforts were conducted using
Cornell Musculoskeletal Discomfort Questionnaire. The data were analyzed using
statistical tests including independent t-test, Chi-square, and ANOVA. The
statistical analysis was performed using SPSS 18. RESULTS: The highest
percentages of complaints related to severe musculoskeletal discomfort were
reported in right shoulder (%36), right wrist (%26), neck (%25), and upper right
arm (%24), respectively. A significant relationship was observed between physical
activity and musculoskeletal discomforts of left wrist (P = 0.012), lower back (P
= 0.016), and neck (P = 0.006). DISCUSSION AND CONCLUSION: Based on the study
results, it can be inferred that regular but not too heavy physical activity can
have a positive impact on decreasing the musculoskeletal discomforts.
PMID- 27512701
TI - The effect of assisted reproduction treatment on mental health in fertile women.
AB - INTRODUCTION: The process of assisted reproductive treatment is a stressful
situation in the treatment of infertile couples and it would harm the mental
health of women. Fertile women who started infertility treatment due to male
factor infertility have reported to experience less stress and depression than
other women before the assisted reproductive process but considering the cultural
and social factors and also the etiology of the assisted reproductive process, it
could affect the metal health of these women. Therefore, this study was conducted
to evaluate the mental health of fertile women who undergo assisted reproductive
treatment due to male factor infertility. MATERIALS AND METHODS: This study was a
prospective study on 70 fertile women who underwent assisted reproductive
treatment due to male factor infertility. The exclusion criterion was to stop
super ovulation induction. To assess mental health, anxiety and depression
dimensions of the general health questionnaire were used. Before starting
ovulation induction and after oocyte harvesting, the general health questionnaire
was filled by women who were under treatment. Data were analyzed using multi
variable linear regression, paired t-test, and Chi-square. RESULTS: The results
showed that the mean score of depression and anxiety before ovulation induction
and after oocyte harvesting were not significantly different; but the rate of
mental health disorder in the depression dimension was significantly decreased
after oocytes harvesting (31.7% vs. 39.7%). Also, there was a significant
relation between the level of anxiety and depression before ovulation induction
and after oocyte harvesting (P < 0.05). The anxiety level after oocyte harvesting
had a positive and significant correlation with the economic situation (P <
0.05). CONCLUSION: This study revealed that the process of assisted reproductive
treatment does not affect the mental health in fertile women independently, but
these women start assisted reproductive process with high levels of depression
and anxiety. Therefore, prior to the assisted reproductive treatment mental
health consultation is needed.
PMID- 27512702
TI - Validity, reliability and factor analysis of Persian version of schizophrenia
quality of life scale.
AB - CONTEXT: Exact measurement of quality of life (QOL) in schizophrenia patients for
evaluation of the patient's deterioration and also to assess the efficacy of
therapeutic Interventions has become a daily task, which requires accurate
assessment tools. AIMS: This study was aimed to assess the psychometric
properties of a Persian version of schizophrenia QOL scale (SQLS) as a common
transcultural instrument. SETTINGS AND DESIGN: One hundred and fifty
schizophrenia patients who referred to Psychiatric Clinic in Noor Hospital
(Isfahan, Iran) have been selected using simple sampling method. SUBJECTS AND
METHODS: Aside with SQLS, short form-36 general health (SF-36) and World Health
Organization QOL-brief-26 (WHOQOL-BREF-26). Questionnaires were completed by the
cases for determination of correlation coefficients. STATISTICAL ANALYSIS USED:
The data were analyzed using descriptive statistics, factor analysis, Cronbach's
coefficient alpha, Pearson correlation coefficient by Statistical Package for
Social Sciences software, version 18 (SPSS-18). RESULTS: Total reliability of the
questionnaire was reported by using Cronbach's coefficient alpha 0.84,
reliability of individual relationships subscales was 0.91, signs 0/87, symptoms
0/72 and motivation/energy 0/61. Correlation coefficients of SF-36 with a total
scale of SQLS and correlation coefficient of WHOQOL-BREF-26 with a total scale of
SQLS were acceptable. Exploratory factor analysis using varimax rotation
identified four principle components (interpersonal relationship, symptoms,
signs, motivation, and energy), which will determine QOL at 52.7% variance.
CONCLUSIONS: Persian version of the SQLS can be used as a simple, reliable and
valid tool in Iranian population.
PMID- 27512703
TI - Prescription to over-the-counter switches in the United States.
AB - As the role of the pharmacist becomes more patient and counseling-centered, the
healthcare market is changing to keep pace with more modern needs, such as self
treatment. Self-treatment provides patients the ability to diagnose their own
condition and pick an appropriate medication from the pharmacy to treat their
symptoms. This process allows a certain freedom for consumers to actively engage
in their own health. In order for patients to self-treat, access to over-the
counter (OTC) medication is of prime importance. Many medications that are
available as OTC today were previously labeled as prescription medications. As
more safety studies and trials are conducted for different drugs, they can be
deemed appropriate for use without a prescription. This review study discusses
the process of switching of prescription medications to OTC medications in the
United States and the implications of switching on patients, practitioners, drug
makers, and insurers.
PMID- 27512704
TI - Pharmaceutical laws and regulations in Iran: An overview.
AB - The pharmaceutical legal framework is a very important infrastructure in
achieving predefined goals in pharmaceutical sector: Accessibility, quality, and
rational use of medicine. This study aims to review the current pharmaceutical
sector-related legal provisions in Iran where the Food and Drug Organization
(FDO) is in charge of regulating all issues related to the pharmaceutical sector.
The main laws and regulations enacted by parliament and cabinet and even internal
regulations enacted by the Ministry of Health or Iran FDO are reviewed. Different
laws and regulations are categorized according to the main goals of Iran national
drug policy.
PMID- 27512705
TI - Critical review of drug promotional literature using the World Health
Organization guidelines.
AB - OBJECTIVE: Drug promotional literatures (DPLs) are used as a promotional tool to
advertise new drugs entering the market to doctors. The objective of the present
study is to evaluate the accuracy of DPLs by using the World Health Organization
(WHO) criteria. METHODS: An observational study was conducted from March to
August 2014. The DPLs were collected from various departments at R.L. Jalappa
Hospital and Research Centre attached to Sri Devaraj Urs Medical College, Kolar,
India. The literature was evaluated based on 11 criteria laid down by the WHO.
FINDINGS: Two-hundred DPLs were evaluated. Cardiovascular drugs (34 [17%]) were
promoted the most, followed by antidiabetic drugs (31 [15.5%]) and antimicrobial
agents (29 [14.5%]). Single drug was promoted in 134 (67%) and fixed drug
combination in 66 (33%) brochures. Manufacturer's name was mentioned in 194
(97%), but their address was mentioned in 109 (54.5%) claims only. Drug cost was
revealed only in 12 (6%) DPLs. Each ingredient's generic name, brand name, and
dosage form were mentioned in 197 (98%) brochures. Indication for use was stated
in 193 (96.5%) claims. Contraindications, adverse effects, precautions, and drug
interactions were listed in 68 (34.5%), 65 (32.5%), 65 (32.5%), and 58 (29%)
advertisements. References were cited in 133 (66.5%) brochures. Only 63 (31.5%)
literatures had relevant pictures of drugs being promoted and 59 (29.5%) had a
graphical representation of pharmacological properties. A total of 131 (69%) DPLs
followed 50% of the WHO criteria. CONCLUSION: Majority of DPLs satisfied only
half of the WHO criteria for rational drug promotion and none of them fulfilled
all the specified criteria. Incomplete or exaggerated information in DPLs may
mislead and result in irrational prescription. Therefore, physicians should
critically evaluate DPLs regarding updated scientific evidence required for
quality patient care.
PMID- 27512706
TI - Tenofovir in treatment of Iranian patients with chronic hepatitis B virus
infection: An open-label case series.
AB - OBJECTIVE: Tenofovir is among the first-line treatments for chronic hepatitis B
(CHB) virus infection. We evaluated the efficacy and safety of Tenofovir in
treatment of Iranian patients with CHB. METHODS: Forty treatment-native patients
with CHB but without concurrent hepatitis C or human immunodeficiency virus
infections were treated with Tenobiovir(TM) 300 mg/day. The hepatitis B virus
(HBV) DNA load, hepatitis B e antigen (HBe Ag), anti-hepatitis B e antibody (HBe
Ab), liver enzymes, and creatinine were measured before and at least 3 months
after the treatment. FINDINGS: The mean age of patients was 38.1 +/- 12.4 years
and 65% of them were male. Seventeen (42.5%) patients were HBe Ag-positive and 15
(37.5%) patients had alanine aminotransferase (ALT) of two times above the
normal. The HBV DNA load was significantly decreased after the treatment (P <
0.001). Twenty-seven (67.5%) patients had viral load of <=2000 IU/ml and 22 (55%)
patients had undetectable HBV DNA level after the treatment. Among positive HBe
Ag patients, the HBe Ag became negative in 15 (88.2%) patients after the
treatment and HBe Ab became positive in 3 (17.6%) patients. Liver enzymes' levels
were significantly decreased after the treatment (P <0.05) and ALT transaminase
level became normalized in 86.7% (13 out of 15) of cases with baseline levels
twice the normal. CONCLUSION: Treatment response rate to Tenofovir in Iranian
patients with CHB was high. The virological and serological response rate and
safety of Tenofovir in our population was comparable to other populations.
Considering availability and costs, Tenobiovir(TM) could be recommended as the
first-line therapy of chronic HBV infection in Iran.
PMID- 27512707
TI - Effect of antiepileptic drug therapy on thyroid hormones among adult epileptic
patients: An analytical cross-sectional study.
AB - OBJECTIVE: The objective of the study was to evaluate and compare the effect of
conventional and newer antiepileptic drugs (AEDs) on thyroid hormone levels in
adult epileptic patients. METHODS: A hospital-based, analytical cross-sectional
study was conducted among the adult epileptic patients receiving conventional
AEDs (Group 2) or newer AEDs (Group 3) for more than 6 months. Serum thyroid
hormone levels including free triiodothyronine (fT3), free thyroxine (fT4), and
thyroid stimulating hormone (TSH) were analyzed and the hormonal status was
compared with healthy control subjects (Group 1). FINDINGS: Sodium valproate and
phenytoin were commonly used conventional AEDs; levetiracetam and topiramate were
common among the newer drugs. There was a statistically significant decrease in
serum fT4 and increase in serum TSH levels (P < 0.0001) in patients on long-term
therapy with conventional antiepileptic agents than in the control group. No
significant change in thyroid hormone levels (fT3, fT4, and TSH; P = 0.68, 0.37,
and 0.90, respectively) was observed with newer antiepileptics-treated patients
when compared to control group. One-way analysis of variance followed by post hoc
Dunnett's test was performed using SPSS version 17.0 software package.
CONCLUSION: The present study showed that conventional AEDs have significant
alteration in the thyroid hormone levels than the newer antiepileptics in adult
epileptic patients.
PMID- 27512708
TI - Malaria rapid diagnostic test evaluation at private retail pharmacies in Kumasi,
Ghana.
AB - OBJECTIVE: Malaria rapid diagnostic test (MRDT) provides a good alternative to
malaria microscopy diagnosis, particularly in resource-constrained settings. This
study therefore evaluated MRDT in private retail pharmacies (PRPs) as a critical
step in community case malaria management. METHODS: In a prospective, cross-over,
validation survey at six PRPs in the Ashanti Region of Ghana, 1200 patients
presenting with fever in the preceding 48 h were sampled. Fingerstick blood
samples were collected for preparation of thick and thin blood films for malaria
microscopy. Categorized patients (600 each) went through the processes of MRDT or
presumptive diagnosis (PD) of malaria. The malaria disease prevalence of the
study area was established. Selectivity (Se), specificity (Sp), positive
predictive value (PPV) along with false discovery rate (FDR), and negative
predictive value (NPV) along with the false omission rate (FOR), and diagnostic
odds ratio (DOR) of MRDT were then calculated. FINDINGS: While 43.0% tested
positive using the MRDT, 57.0% tested negative. However, 62.0% MRDT-negative
patients in addition to all the MRDT positives were given artemether
lumefantrine. Of those diagnosed by PD, 98.2% were prescribed with an
antimalarial (microscopy however confirmed only 70.3% as positive). Se and Sp of
the MRDT were 90.68 +/- 11.18% and 98.68 +/- 1.19%, respectively. Malaria
prevalence was estimated to be 43.3%. PPV was 98.0%, FDR was 2.0%, NPV was 98.0%,
FOR was 2.0%, and DOR was 2366.43. CONCLUSION: Results highlighted good
performance of MRDTs at PRPs which could inform decision toward its
implementation.
PMID- 27512709
TI - Quality of life in relapsing-remitting multiple sclerosis patients receiving
CinnoVex compared with Avonex.
AB - OBJECTIVE: There is an increasing recognition among clinicians and researchers
that the impact of chronic illnesses and their treatments must be assessed in
terms of their quality of life (QoL) in addition to more traditional measures of
clinical outcomes. The aim of this study was to compare the QoL in patients with
relapsing-remitting multiple sclerosis (RRMS) using Avonex or CinnoVex. METHODS:
We conducted a cross-sectional study on one hundred patients with RRMS, fifty and
fifty patients were being treated with Avonex (Biogen Idec, USA) and CinnoVex
(CinnaGen, Iran), respectively. We used a disease-specific questionnaire for MS
(Multiple Sclerosis Quality of Life-54 [MSQoL-54]). Both groups were tested for
significant differences regarding sociodemographic. A multiple linear regression
model was constructed to find factors that affected the different aspect of QoL
of the whole sample of patients. FINDINGS: MS groups did not differ in physical
and mental health composite scores as well as relative scales. The results of
regression models for each subscale showed that age, marriage, and Expanded
Disability Status Scale were associated with several subscales of the MSQoL-54 (P
< 0.05). CONCLUSION: In this study, it was seen that there are no significant
differences between QoL of Avonex and CinnoVex, but a limitation in our study the
results may be different in other countries and even various areas in Iran.
PMID- 27512710
TI - Adherence to stress-related mucosal damage prophylaxis guideline in patients
admitted to the Intensive Care Unit.
AB - OBJECTIVE: Concern about adverse effects of the inconsistent use of stress
related mucosal damage prophylaxis in intensive care unit (ICU) is increasing.
Hence, this study was designed to prospectively evaluate the rate of
inappropriate stress ulcer prophylaxis (SUP) administration upon ICU admission,
at ICU discharge and determine the adherence to American Society of Health-System
Pharmacists (ASHP) guideline during ICU stay. METHODS: In this study, 200
patients were randomly selected from all ICU admissions during 9 months. Risk
factors of stress ulcer were recorded daily during ICU stay and appropriateness
of SUP administration was assessed according to the ASHP criteria. FINDINGS: Of
all 160 (80%) patients who received SUP, 44.4% did not have indication; and among
95 patients with an indication for SUP administration, 6.3% did not receive it
upon ICU admission. Consequently, 77 (38.5%) of 200 patients received
inappropriate prophylaxis on ICU admission. In addition, 53.5% of patients had
appropriate adherence to ASHP guideline during all days of ICU stay (44% and 2.5%
of patients received SUP more than 120% and <80% of appropriate SUP duration,
respectively). Moreover, 81.2% were continued on inappropriate prophylaxis upon
transfer from the ICU. CONCLUSION: We concluded that although SUP administration
included both overutilization and underutilization in this ICU, but high
prevalence of SUP overutilization caused unnecessary hospital costs, personal
monetary burden, and may increase adverse drug reactions. Therefore, educating
physicians and cooperation of clinical pharmacists regarding implementing
standard protocols could improve patterns of SUP administration.
PMID- 27512711
TI - The use of sunscreen products among final year medicine and pharmacy students: A
cross-sectional study of knowledge, attitude, practice, and perception.
AB - OBJECTIVE: To evaluate the knowledge, attitude, perception, and practice of
medical and pharmacy students toward the usage of sunscreen as protection for the
skin against ultraviolet (UV) radiation. METHODS: This cross-sectional study was
conducted among final year medical and pharmacy undergraduates at the
International Islamic University Malaysia. Validated questionnaires were
distributed to 134 medical students and 100 pharmacy students. Descriptive and
inferential statistics were used where appropriate. FINDINGS: One hundred and
sixty-one out of 234 participants completed the questionnaires. The participants
comprised 101 medical students (75.4%) and sixty pharmacy students (60.0%). The
majority of the respondents were females (102; 63.4%), and 59 (36.6%) were males.
The median of the knowledge scores of the final year medical students was
significantly lower than that of the final year pharmacy students (P < 0.001).
The female students showed significantly higher knowledge scores than the male
students (P = 0.027). This study reported that 24 (39.3%) pharmacy students were
influenced by the media to use sunscreen, whereas 35 (34.7%) medical students
were influenced the most by friends to use sunscreen. The final year pharmacy
students had a better perception compared to the medical students, with the total
perception score of the final year pharmacy students being significantly higher
than that of the final year medical students (P = 0.020). Most of the
participants were also aware of the harmful effects of UV radiation and had a
positive reaction toward the usage of sunscreen to prevent those harmful effects.
CONCLUSION: The knowledge and perception of final year pharmacy students were
significantly higher than the knowledge and perception of final year medical
students with regard to the usage of sunscreen.
PMID- 27512712
TI - Evaluation of knowledge, attitude, and practice of community pharmacists toward
administration of over-the-counter drugs for the treatment of diarrhea in
children: A pretest-posttest survey.
AB - OBJECTIVE: In this study, we aimed to assess knowledge, attitude, and practice of
community pharmacists toward administration of over-the-counter (OTC)
antidiarrheal drugs in our city pharmacies, Shiraz, Iran. METHODS: In this
descriptive cross-sectional study, 90 pharmacies among 128 pharmacies in our city
were randomly chosen. The study was designed into two phases: A standard
questionnaire to determine the level of knowledge and attitude of pharmacists and
a simulated client method to evaluate practice among them. An educational
pamphlet was then given to the pharmacists. One month later, knowledge, attitude,
and performance of studied pharmacists were evaluated again using the same
method. FINDINGS: Our results showed that an average consultation time by female
pharmacists was considerably more than male pharmacists (P < 0.001). Before
intervention, only 37.8% of pharmacists performed appropriately by prescribing
the proper medicine while this increased to 58.44% after intervention. The
average score of pharmacists' knowledge was statistically increased (P < 0.001)
and the pharmacists' performance was significantly improved (P < 0.001) after the
educational intervention. In related to the attitude, pharmacists' tendency
toward prescribing oral rehydration salt solutions (ORS) (P < 0.001) and their
belief about the great effect of ORS on the treatment of diarrhea increased
significantly after the intervention. CONCLUSION: It is concluded that training
programs such as educational pamphlets and continuing educational seminars may
play important roles in increasing pharmacists' knowledge and therefore improving
their performance in prescribing OTC medicines.
PMID- 27512713
TI - Clinical outcomes of a diabetes education program for patients with diabetes
mellitus in the Micronesian community in Hawaii.
AB - OBJECTIVE: Hawaii has diverse population made up of a cultural mix of different
races. Due to different cultural and social influences and language barrier, many
of the under-served population who migrated to Hawaii and having diabetes
mellitus may be susceptible to long-term complications due to uncontrolled
hyperglycemia and medication nonadherence. The purpose of this study was to
evaluate the impact of a diabetes education program on the clinical outcomes in
patients with diabetes mellitus in the Micronesian community of Hawaii. METHODS:
This study included patients over age 18 years, with a diagnosis of type 2
diabetes mellitus. The diabetes education program was customized for its weekly
classes to fit to the under-served population. Data were collected on
participants on the 1(st) day and then 6 months after attending the education
program. Data on primary and secondary endpoints were collected and analyzed.
FINDINGS: The mean glycosylated hemoglobin A1c, fasting blood glucose, and
triglyceride levels of participants fell significantly from baseline after
attending the diabetes education program for 6 months. No significant changes
were observed in other secondary outcomes during the study time period.
CONCLUSION: Based on our findings, the diabetes education program that was
tailored to the Micronesian population was successful in achieving glycemic
goals, enhancing medication adherence, improving clinical outcomes, and also
preventing long-term complications among its participants.
PMID- 27512714
TI - Ganciclovir use evaluation in kidney transplantation departments.
AB - OBJECTIVE: In this study, we evaluated certain aspects of the usage and
administration of one lifesaving, high-cost medication, i.e., Ganciclovir for the
prevention and treatment of cytomegalovirus (CMV) infection in transplant
patients. METHODS: This study was performed from 2013 to 2015 by conducting a
medication use evaluation (MUE) program in the kidney transplantation departments
of two tertiary care hospitals in Isfahan, Iran. The MUE criteria for the drug
were developed by applying drug information references. In every category of
data, the number (percent) of cases, in which drug therapy was in accordance with
the predetermined criteria, was calculated. FINDINGS: During the study period, 67
cases were observed. The only documented drug interaction was the minor
interaction of Ganciclovir with mycophenolate mofetil in 77% of the patients. In
all patients, intravenous (IV) infusion was the route of administration, mainly
in the peripheral veins. Four patients showed adverse drug reaction, which leads
to Ganciclovir discontinuation. Ganciclovir was administered despite
contraindication in 34.3% of the patients. CONCLUSION: In this study, we faced a
relatively unacceptable situation, in which Ganciclovir is handled somehow
inappropriately. It seems necessary to develop an updated local guideline to
approximate the administering pattern of such costly medications to standard
protocols.
PMID- 27512715
TI - Dapsone-induced pure red cell aplasia and cholestatic jaundice: A new experience
for diagnosis and management.
AB - Dapsone (4,4'- diaminodiphenylsulfone) is the parent compound of the sulfones,
and it has potent antiparasitic, anti-inflammatory, and immunomodulatory effects.
It is used in the treatment of leprosy, dermatitis herpetiformis, and
prophylactically to prevent Pneumocystis pneumonia and toxoplasmosis in patients
unable to tolerate trimethoprim with sulfamethoxazole. We hereby report a case of
dapsone toxicity who developed pure red cell aplasia and cholestatic jaundice in
a suspected case of dermatitis herpetiformis. Patient had an excellent response
to corticosteroids after withdrawal of dapsone.
PMID- 27512716
TI - Attitude of nurses and pharmacists on adverse drug reactions reporting in
selected hospitals in Sokoto, Northwest Nigeria.
AB - OBJECTIVE: Objective of this study was to assess the attitude of nurses and
pharmacists towards adverse drug reactions (ADRs) reporting. METHODS: The
questionnaire was designed based on extended "Inman seven deadly sins." Two
hundred and seventy-two respondents were selected by stratified sampling
technique. The questionnaires were delivered to the respondents at their places
of practice. The data generated were analyzed by Sigma XL Software Inc. FINDINGS:
There was no statistically significant relationship between demographic profiles
and reporting attitude except for qualification. On extended "Inman seven deadly
sins" awareness of reporting protocol and nearby center for ADRs reporting were
low 27.3 and 7.5%, respectively. However, respondents' score on components of
attitude of ADRs reporting is generally encouraging. On comparative basis, no
statistical significance exists between pharmacists and nurses. CONCLUSION: The
study showed that attitude of respondents towards ADRs reporting is good.
However, there is a need for targeted health education intervention among these
cadres of health-care professionals, especially on aspects of awareness of
reporting protocol and reporting center.
PMID- 27512717
TI - A study of medication-related problems in stroke patients: A need for
pharmaceutical care.
AB - OBJECTIVE: The study was aimed to assess the incidence and characteristics of
drug-related problems (DRPs). METHODS: A prospective, observational study was
conducted among 133 patients with stroke disease who were aged 18 years or older
and admitted to the general medicine ward. During the 6 months study period, the
incidence of DRPs was identified using the Pharmaceutical Care Network Europe
Foundation classification system, version 6.2. FINDINGS: A total of 133 patients
were screened for DRPs. Among them, 120 patients have at least one DRP. A total
of 254 DRPs were identified (on average, 2.015 DRPs per each patient case).
CONCLUSION: Increasing the evidence of the incidence of medication-related
problems in tertiary care hospitals indicates the need for the establishment of a
clinical pharmacist in hospital settings.
PMID- 27512718
TI - A High Concentration of Genistein Induces Cell Death in Human Uterine Leiomyoma
Cells by Autophagy.
AB - Genistein, an estrogenic, soy-derived isoflavone, may play a protective role
against hormone-related cancers. We have reported that a high concentration of
genistein inhibits cell proliferation and induces apoptosis in human uterine
smooth muscle cells, but not in leiomyoma (fibroid) cells. To better understand
the differential cell death responses of normal and tumor cells to a high
concentration of genistein, we treated uterine smooth muscle cells and uterine
leiomyoma cells with 50 MUg/ml of genistein for 72 h and 168 h, and assessed for
mediators of apoptosis, cytotoxicity and autophagy. We found that leiomyoma cells
had increased protection from apoptosis by expressing an increased ratio of Bcl
2: bak at 72 h and 168 h; however, in smooth muscle cells, the Bcl-2: bak ratio
was decreased at 72 h, but significantly rebounded by 168 h. The apoptosis
extrinsic factors, Fas ligand and Fas receptor, were highly expressed in uterine
smooth muscle cells following genistein treatment at both time points as
evidenced by confocal microscopy. This was not seen in the uterine leiomyoma
cells; however, cytotoxicity as indicated by elevated lactate dehydrogenase
levels was significantly enhanced at 168 h. Increased immunoexpression of an
autophagy/autophagosome marker was also observed in the leiomyoma cells, although
minimally present in smooth muscle cells at 72 h. Ultrastructurally, there was
evidence of autophagic vacuoles in the leiomyoma cells; whereas, the normal
smooth muscle cells showed nuclear fragmentation indicative of apoptosis. In
summary, our data show differential cell death pathways induced by genistein in
tumor and normal uterine smooth muscle cells, and suggest novel cell death
pathways that can be targeted for preventive and intervention strategies for
inhibiting fibroid tumor cell growth in vivo.
PMID- 27512719
TI - Ex vivo testing of intact eye globes under inflation conditions to determine
regional variation of mechanical stiffness.
AB - BACKGROUND: The eye globe exhibits significant regional variation of mechanical
behaviour. The aim of this present study is to develop a new experimental
technique for testing intact eye globes in a form that is representative of in
vivo conditions, and therefore suitable for determining the material properties
of the complete outer ocular tunic. METHODS: A test rig has been developed to
provide closed-loop control of either applied intra-ocular pressure or resulting
apical displacement; measurement of displacements across the external surface of
the eye globe using high-resolution digital cameras and digital image correlation
software; prevention of rigid-body motion and protection of the ocular surface
from environmental drying. The method has been demonstrated on one human and one
porcine eye globe, which were cyclically loaded. Finite element models based on
specimen specific tomography, free from rotational symmetry, were used along with
experimental pressure-displacement data in an inverse analysis process to derive
the mechanical properties of tissue in different regions of the eye's outer
tunic. RESULTS: The test method enabled monitoring of mechanical response to
intraocular pressure variation across the surface of the eye globe. For the two
eyes tested, the method showed a gradual change in the sclera's stiffness from a
maximum at the limbus to a minimum at the posterior pole, while in the cornea the
stiffness was highest at the centre and lowest in the peripheral zone. Further,
for both the sclera and cornea, the load-displacement behaviour did not vary
significantly between loading cycles. CONCLUSIONS: The first methodology capable
of mechanically testing intact eye globes, with applied loads and boundary
conditions that closely represent in vivo conditions is introduced. The method
enables determination of the regional variation in mechanical behaviour across
the ocular surface.
PMID- 27512720
TI - Can Genetic Testing Coupled with Enhanced Dopaminergic Activation Reduce
Recidivism Rates in the Workers Compensation Legacy Cases?
PMID- 27512721
TI - Factors Associated With Emergency Department Visits: A Multistate Analysis of
Adult Fee-for-Service Medicaid Beneficiaries.
AB - OBJECTIVE: The objective of this study was to examine the association of patient-
and county-level factors with the emergency department (ED) visits among adult
fee-for-service (FFS) Medicaid beneficiaries residing in Maryland, Ohio, and West
Virginia. METHODS: A cross-sectional design using retrospective observational
data was implemented. Patient-level data were obtained from 2010 Medicaid
Analytic eXtract files. Information on county-level health-care resources was
obtained from the Area Health Resource file and County Health Rankings file.
RESULTS: In adjusted analyses, the following patient-level factors were
associated with higher number of ED visits: African Americans (incidence rate
ratios [IRR] = 1.47), Hispanics (IRR = 1.63), polypharmacy (IRR = 1.89), and
tobacco use (IRR = 2.23). Patients with complex chronic illness had a higher
number of ED visits (IRR = 3.33). The county-level factors associated with ED
visits were unemployment rate (IRR = 0.94) and number of urgent care clinics (IRR
= 0.96). CONCLUSION: Patients with complex healthcare needs had a higher number
of ED visits as compared to those without complex healthcare needs. The study
results provide important baseline context for future policy analysis studies
around Medicaid expansion options.
PMID- 27512722
TI - Alopecia areata after denosumab treatment for osteoporosis.
PMID- 27512723
TI - Identification of Asthma Subtypes Using Clustering Methodologies.
AB - Asthma is a heterogeneous disease comprising a number of subtypes which may be
caused by different pathophysiologic mechanisms (sometimes referred to as
endotypes) but may share similar observed characteristics (phenotypes). The use
of unsupervised clustering in adult and paediatric populations has identified
subtypes of asthma based on observable characteristics such as symptoms, lung
function, atopy, eosinophilia, obesity, and age of onset. Here we describe
different clustering methods and demonstrate their contributions to our
understanding of the spectrum of asthma syndrome. Precise identification of
asthma subtypes and their pathophysiological mechanisms may lead to
stratification of patients, thus enabling more precise therapeutic and prevention
approaches.
PMID- 27512724
TI - Optimization of a Clinically Relevant Model of White Matter Stroke in Mice:
Histological and Functional Evidences.
AB - BACKGROUND AND PURPOSE: White matter (WM) injury during stroke increases the risk
of disability and gloomy prognosis of post-stroke rehabilitation. However,
modeling of WM loss in rodents has proven to be challenging. METHODS: We report
improved WM injury models in male C57BL/6 mice. Mice were given either endothelin
1 (ET-1) or L-N5-(1-iminoethyl)ornitine (L-NIO) into the periventricular white
matter (PVWM), in the corpus callosum (CC), or in the posterior limb of internal
capsule (PLIC). Anatomical and functional outcomes were quantified on day 7 post
injection. RESULTS: Injection of ET-1 or L-NIO caused a small focal lesion in the
injection site in the PVWM. No significant motor function deficits were observed
in the PVWM lesion model. We next targeted the PLIC by using single or double
injections of L-NIO and found that this strategy induced small focal infarction.
Interestingly, injection of L-NIO in the PLIC also resulted in gliosis, and
significant motor function deficits. CONCLUSIONS: By employing different agents,
doses, and locations, this study shows the feasibility of inducing brain WM
injury accompanied with functional deficits in mice. Selective targeting of the
injury location, behavioral testing, and the agents chosen to induce WM injury
are all keys to successfully develop a mouse model and subsequent testing of
therapeutic interventions against WM injury.
PMID- 27512725
TI - Large tumor suppressors 1 and 2 regulate Aurora-B through phosphorylation of
INCENP to ensure completion of cytokinesis.
AB - The tumor suppressor kinases LATS1 and LATS2 (LATS1/2) regulate not only organ
size through the Hippo signaling pathway, but also cell-cycle checkpoints and
apoptosis via other signaling cascades. We previously reported that LATS1/2
localize to the mitotic apparatus, where they are involved in the phosphorylation
and activation of the mitotic kinase Aurora-B; however, the detailed mechanism of
LATS1/2 action remains obscure. The activity of Aurora-B is stringently regulated
by formation of the chromosomal passenger complex containing the inner centromere
protein (INCENP), which leads to appropriate activation of Aurora-B during
mitosis and cytokinesis. In this study, we found that LATS1/2 phosphorylated
INCENP at S894 in the Thr-Ser-Ser motif. Moreover, the LATS-mediated
phosphorylation of S894 was necessary and sufficient for the activation of Aurora
B, which is required for completion of cytokinesis in cells engaged in multipolar
division. We propose a novel mechanism for regulation of Aurora-B via INCENP
phosphorylation by LATS1/2 during cytokinesis.
PMID- 27512728
TI - Preparation and characterization of lithium ion conducting polymer electrolytes
based on a blend of poly(vinylidene fluoride-co-hexafluoropropylene) and
poly(methyl methacrylate).
AB - Ion conducting polymer electrolytes composed of poly(vinylidene fluoride-co
hexafluoropropylene) (PVdF-HFP), poly(methyl methacrylate) (PMMA) and lithium
triflate (LiTf) were prepared using the solution casting method. Structural
change and complex formation in the blend electrolyte systems were confirmed from
the X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and
scanning electron microscopy (SEM) studies. Thermal properties of the samples
were investigated by the differential scanning calorimetry (DSC) technique. The
ionic conductivity of these polymer electrolytes was studied by impedance
spectroscopy at various temperatures ranging from 303-393 K. The results reveal
that the ionic conductivity of the polymer blend electrolytes depends on the PVdF
HFP:PMMA composition as well as the temperature. Maximum room temperature
conductivity of [Formula: see text] S cm(-1) was achieved with 22.5 wt.% PMMA.
The blending of PVdF-HFP with PMMA improved the thermal stability and ionic
conductivity of the polymer electrolyte. Estimated transference numbers suggest
the charge transport is predominantly ionic.
PMID- 27512727
TI - A small molecule-based strategy for endothelial differentiation and three
dimensional morphogenesis from human embryonic stem cells.
AB - The emerging models of human embryonic stem cell (hESC) self-organizing organoids
provide a valuable in vitro platform for studying self-organizing processes that
presumably mimic in vivo human developmental events. Here we report that through
a chemical screen, we identified two novel and structurally similar small
molecules BIR1 and BIR2 which robustly induced the self-organization of a balloon
shaped three-dimensional structure when applied to two-dimensional adherent hESC
cultures in the absence of growth factors. Gene expression analyses and
functional assays demonstrated an endothelial identity of this balloon-like
structure, while cell surface marker analyses revealed a VE
cadherin(+)CD31(+)CD34(+)KDR(+)CD43(-) putative endothelial progenitor
population. Furthermore, molecular marker labeling and morphological examinations
characterized several other distinct DiI-Ac-LDL(+) multi-cellular modules and a
VEGFR3(+) sprouting structure in the balloon cultures that likely represented
intermediate structures of balloon-formation.
PMID- 27512726
TI - 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone inhibits LPS-induced BV2
microglial activation through MAPK/NF-kB signaling pathways.
AB - AIMS: To verify the effects of several 5,8-dimethoxy-1,4-naphthoquinone (DMNQ)
derivatives on LPS-induced NO production, cellular ROS levels and cytokine
expression in BV-2 microglial cells. MAIN METHODS: An MTT assay and FACS flow
cytometry were performed to assess the cellular viability and apoptosis and
cellular ROS levels, respectively. To examine the expression of pro-inflammatory
cytokines and cellular signaling pathways, semi-quantitative RT-PCR and Western
blotting were also used in this study. KEY FINDINGS: Among the six newly
synthesized DMNQ derivatives, 2-cyclohexylamino-5,8-dimethoxy-1,4-naphthoquinone
(R6) significantly inhibited the NO production, cellular ROS levels and the
cytokines expression in BV-2 microglial cells, which stimulated by LPS. Signaling
study showed that compound R6 treatment also significantly down-regulated the LPS
induced phosphorylation of MAPKs (ERK, JNK and p38) and decreased the degradation
of IkappaB-alpha in BV2 microglial cells. SIGNIFICANCE: Our findings demonstrate
that our newly synthesized compound derived from DMNQ, 2-cyclohexylamino-5,8
dimethoxy-1,4-naphthoquinone (R6), might be a therapeutic agent for the treatment
of glia-mediated neuroinflammatory diseases.
PMID- 27512729
TI - Histomorphometric parameters of normal full term placenta of Sudanese women.
AB - The aim of the study was to provide values for morphometric parameters of
histological components of normally delivered full term placentas of Sudanese
women and compare them with reported parameters for other ethnic groups. A total
of 200 histological sections, stained with hematoxylin and eosin and trichrome
stains were used to give a final sample of 1000 fields saved as PowerPoint images
for histomorphometry. A systematic random sampling procedure was adopted to
ensure the optimum sample size that keeps the percentage error below 5% for the
volume estimates. Standard stereological methods of point-counting and
intersection-counting were applied to the microscopic fields to determine the
volumes of placental components and surface area of fetal-maternal interface. The
morphometric parameters showed no variations either between the placentas or
between central and peripheral regions. The placental villi and the intervillus
space occupied 65% and 35% of placental volume respectively with mean absolute
values of 318 cm(3) and 169 cm(3). The mean absolute volume of the intervillus
space was less than that of other ethnic groups by 8.67% but was significantly
larger than that of the fetal capillaries which measured 41.2 cm(3). The ratio of
the absolute volume of the intervillus space to the volume of the fetal blood
capillaries was 4:1 in both Sudanese and other ethnic groups. In the placental
villi the fetal connective tissue together with the contained blood vessels
larger than capillaries occupied 88% of the villus volume. The mean surface area
of the fetal-maternal interface of the placental villi (syncytiotrophoblast) was
12.59 M(2).
PMID- 27512730
TI - Genetic factors for alcohol dependence and schizophrenia: common and rare
variants.
PMID- 27512731
TI - Angiotensin Receptors: Structure, Function, Signaling and Clinical Applications.
AB - Angiotensinogen - a serpin family protein predominantly produced by the liver is
systematically processed by proteases of the Renin Angiotensin system (RAS)
generating hormone peptides. Specific cell surface receptors for at least three
distinct angiotensin peptides produce distinct cellular signals that regulate
system-wide physiological response to RAS. Two well characterized receptors are
angiotensin type 1 receptor (AT1 receptor) and type 2 receptor (AT2 receptor).
They respond to the octapeptide hormone angiotensin II. The oncogene product MAS
is a putative receptor for Ang (1-7). While these are G-protein coupled receptors
(GPCRs), the in vivo angiotensin IV binding sites may be type 2 transmembrane
proteins. These four receptors together regulate cardiovascular, hemodynamic,
neurological, renal, and endothelial functions; as well as cell proliferation,
survival, matrix-cell interactions and inflammation. Angiotensin receptors are
important therapeutic targets for several diseases. Thus, researchers and
pharmaceutical companies are focusing on drugs targeting AT1 receptor than AT2
receptor, MAS and AngIV binding sites. AT1 receptor blockers are the cornerstone
of current treatment for hypertension, heart failure, renal failure and many
types of vascular diseases including atherosclerosis, aortic aneurism and Marfan
syndrome.
PMID- 27512732
TI - Dynamic view of postoperative pain evolution after total knee arthroplasty: a
prospective observational study.
AB - BACKGROUND: Having a dynamic view of postoperative pain resolution allows a
better understanding of the transition towards chronic pain. Sleep and quality of
life are important determinants of satisfaction after total knee arthroplasty
(TKA), besides functional recovery and pain. METHODS: For 114 patients undergoing
TKA we recorded the presence of pain at rest, pain evoked at movement and pain
located at the incision site in the acute (postoperative day 1, 2, 3, 8),
subacute (30 days, 3 months) and chronic (6 months and 1 year) period. Analgesics
consumption and need of medical assistance for pain were questioned. Quality of
life measured by the impact on enjoyment of life, sleep and mood were monitored.
RESULTS: Average incidence for subacute pain was 54% at rest, 66% at
mobilization. For chronic pain, the incidence was 14% at rest, 22% during
mobilization. Pain at rest peaked at day 30 while pain during mobilization
displayed a plateau between day 8 and 3 months. Three per cent of the patients
complained at 1 year of pain at the incision site. 11% of patients still took
analgesics one year after the surgery. More than 40% of patients reported
moderate to severe alterations of sleep and quality of life in the acute period,
decreasing to less than a half at one year. CONCLUSIONS: The trajectories of the
different types of pain after TKA show their non-linear evolution, highlighting
the need of a better pain control at precise moments. Sleep disturbances and
alterations of quality of life are still present one year after the surgery.
PMID- 27512733
TI - Resolution of osteosclerosis after alloHCT in systemic mastocytosis.
PMID- 27512734
TI - CardioPulse: Regenerative medicine in the practice of cardiology.
PMID- 27512735
TI - CardioPulse: Translational research in cardiovascular disease.
PMID- 27512736
TI - CardioPulse: Progress in gene therapy for cardiovascular disease.
PMID- 27512737
TI - CardioPulse: Gene linked to heart disease in women.
PMID- 27512738
TI - [S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease].
PMID- 27512739
TI - Response.
PMID- 27512816
TI - The effects of passive stretching plus vibration on strength and activation of
the plantar flexors.
AB - This study examined the effects of passive stretching only (PS+CON) and passive
stretching with the addition of continuous vibration (VIB) during post-passive
stretching tests (PS+VIB) on peak torque (PT), percent voluntary inactivation
(%VI), single stimulus twitch torque (TTSINGLE), and doublet stimuli twitch
torque (TTDOUBLET) of the plantar flexors at a short (20 degrees plantar flexion
(PF)) and long muscle length (15 degrees dorsiflexion (DF)). Fourteen healthy
men (age = 22 +/- 3 years) performed isometric maximal voluntary contractions at
PF and DF, and passive range of motion (PROM) assessments before and after 8 * 30
s passive stretches without (PS+CON) or with VIB (PS+VIB) administered
continuously throughout post-passive stretching tests. The passive properties of
the muscle tendon unit were assessed pre- and post-passive stretching via PROM,
passive torque (PASSTQ), and musculotendinous stiffness (MTS) measurements. PT,
TTSINGLE, and TTDOUBLET decreased, whereas, %VI increased following passive
stretching at PF and DF (P < 0.05) with no significant differences between PS+CON
and PS+VIB. PASSTQ and MTS decreased while PROM increased post-passive stretching
during both trials (P < 0.05). The stretching-induced force/torque deficit and
increases in %VI were evident following passive stretching at short and long
muscle lengths. Although not statistically significant, effect size calculations
suggested large and moderate differences in the absolute changes in PT (Cohen's d
= 1.14) and %VI (Cohen's d = 0.54) from pre- to post-passive stretching between
treatments, with PS+VIB having greater decreases of PT and higher %VI than
PS+CON. The decrement in PT following passive stretching may be primarily neural
in origin.
PMID- 27512815
TI - "Weighing" the effects of exercise and intrinsic aerobic capacity: are there
beneficial effects independent of changes in weight?
AB - It has been known for centuries that regularly performed exercise has beneficial
effects on metabolic health. Owing to its central role in locomotion and the fact
that it accounts for a large majority of whole-body glucose disposal and fatty
acid oxidation, the effects of exercise on skeletal muscle has been a central
focus in exercise physiology research. With this being said it is becoming
increasingly well recognized that both adipose tissue and liver metabolism are
robustly modified by exercise, especially in conditions of obesity and insulin
resistance. One of the difficult questions to address is if the effects of
exercise are direct or occur secondary to exercise-induced weight loss. The
purpose of this review is to highlight recent work that has attempted to tease
out the protective effects of exercise, or intrinsic aerobic capacity, against
metabolic and inflammatory challenges as it relates to the treatment and
prevention of obesity and insulin resistance. Recent studies reporting
improvements in liver and adipose tissue insulin action following a single bout
of exercise will also be discussed. The research highlighted in this review sheds
new insight into protective, anti-inflammatory effects of exercise that occur
largely independent of changes in adiposity and body weight.
PMID- 27512817
TI - Hydride-Based Electride Material, LnH2 (Ln = La, Ce, or Y).
AB - In view of the strong electron-donating nature of H(-) and extensive vacancy
formation in metals by hydrogen insertion, a series of LnH2+x (Ln = La, Ce, or Y)
compounds with fluorite-type structures were verified to be the first hydride
based electride, where itinerant electrons populating the cage are surrounded by
H(-) anions. The electron transfer into the cage probably originates from Ln-cage
covalent interaction. To the best of our knowledge, anion-rich electrides are
extremely rare, and a key requirement for their formation is that the cage site
is not occupied by lone pair electrons of the adjacent ions. In the case of LnH2,
the cage site is surrounded by eight H(-) anions with isotopic electronic
character caused by the lack of mixing of H p-orbital character. Notably, Ru
loaded LnH2+x electride powders synthesized by hydrogen embrittlement (Ln = La or
Ce) were found to work as efficient catalysts for ammonia synthesis at ambient
pressure, without showing serious signs of hydrogen poisoning. There are several
possible origins of the observed high catalytic activity in the hydride
promotors: the small work function of LnH2+x derived from the covalent
interaction between Ln cation and the H(-) sigma donor, and the formation of Ln
nitride during catalytic reaction.
PMID- 27512820
TI - Hand preferences for unimanual and bimanual coordinated actions in olive baboons
(Papio anubis): Consistency over time and across populations.
AB - The reliability of handedness data in nonhuman primates and variations of sample
size across studies are critical issues for exploring their potential continuity
with humans concerning hemispheric specialization. In this study, we investigated
the consistency of handedness for unimanual and bimanual tasks in olive baboons
(Papio anubis). For both tasks, we found a consistency of hand preferences over
time among subjects retested 5 years later and a consistency of population-level
handedness between 2 independent populations. Altogether, when combining the 2
samples, bimanual (N = 260) but not unimanual task (N = 220) elicited right
handedness predominance. These findings demonstrate the reliability and
robustness of predominance of right-handedness in olive baboons for bimanual
coordinated behaviors. (PsycINFO Database Record
PMID- 27512818
TI - Molecular and Dynamic Mechanism Underlying Drug Resistance in Genotype 3
Hepatitis C NS3/4A Protease.
AB - Hepatitis C virus (HCV), affecting an estimated 150 million people worldwide, is
the leading cause of viral hepatitis, cirrhosis and hepatocellular carcinoma. HCV
is genetically diverse with six genotypes (GTs) and multiple subtypes of
different global distribution and prevalence. Recent development of direct-acting
antivirals against HCV including NS3/4A protease inhibitors (PIs) has greatly
improved treatment outcomes for GT-1. However, all current PIs exhibit
significantly lower potency against GT-3. Lack of structural data on GT-3
protease has limited our ability to understand PI failure in GT-3. In this study
the molecular basis for reduced potency of current inhibitors against GT-3 NS3/4A
protease is elucidated with structure determination, molecular dynamics
simulations and inhibition assays. A chimeric GT-1a3a NS3/4A protease amenable to
crystallization was engineered to recapitulate decreased sensitivity of GT-3
protease to PIs. High-resolution crystal structures of this GT-1a3a bound to 3
PIs, asunaprevir, danoprevir and vaniprevir, had only subtle differences relative
to GT-1 despite orders of magnitude loss in affinity. In contrast, hydrogen
bonding interactions within and with the protease active site and dynamic
fluctuations of the PIs were drastically altered. The correlation between loss of
intermolecular dynamics and inhibitor potency suggests a mechanism where
polymorphisms between genotypes (or selected mutations) in the drug target confer
resistance through altering the intermolecular dynamics of the protein-inhibitor
complex.
PMID- 27512821
TI - Differences in shoaling behavior in two species of freshwater fish (Danio rerio
and Hyphessobrycon herbertaxelrodi).
AB - Fish can gain significant adaptive advantages when living in a group and they
exhibit a wide variety of types of collective motion. The scientific literature
recognizes 2 main patterns: shoals (aggregations of individuals that remain close
to each other), and schools (aggregations of aligned, or polarized, individuals).
We analyzed the collective motion of 2 social fish species, zebrafish (Danio
rerio) and black neon tetra (Hyphessobrycon herbertaxelrodi), and compared their
patterns of movement and the effect of group size and environmental constraints
such as water column height and tank geometry on the collective motion of both
species. We recorded the movement of groups of fish (n = 10 and n = 20) using 2
tank geometries: a rectangular shape and a rectangular shape with rounded
corners; and we also manipulated the water column height (15 and 25 cm). We
extracted the individual fish trajectories and calculated indices of cohesion,
coordination, group density and group shape. The results showed that the 2
species had different types of collective motion: the zebrafish's global motion
matched that of a shoal, while the black neon tetra's motion matched that of a
school. Indirect evidence indicated that the 2 species tended to occupy the
vertical space differently while swimming in a group. Finally, we found that tank
geometry did not affect group polarization, whereas group size had an effect on
black neon tetra density, which was higher in small group sizes than in large
ones. (PsycINFO Database Record
PMID- 27512822
TI - Reasoning versus association in animal cognition: Current controversies and
possible ways forward.
AB - The study of animal cognition is rife with controversy, and among the most long
standing and most intensely debated controversies in the field is the question of
the extent to which the behavior of nonhuman animals can be fully understood on
the basis of purely associative principles, or whether some behaviors exhibited
by animals necessitate the assumption of inferential capacities in animals that
defy an associative explanation. Remarkably, the continuing debate on the topic
seems to be spawning little genuine progress in terms of substantial accumulation
of new, generally accepted insights. As an introduction to a special section of
the Journal of Comparative Psychology on the topic, the present article outlines
a number of reasons for the stalemate and suggests ways to refertilize the
debate. In particular, we claim that progress will not come from the adoption of
general principles like Morgan's canon or the primacy of prediction over
postdiction. Instead, emphasis should be placed on a careful analysis of what it
is that different sides in the debate do and do not agree on and an increased
willingness to engage in adversarial collaboration, in the spirit of a shared
interest in furthering our understanding of animal behavior.
PMID- 27512823
TI - Beyond the information (not) given: Representations of stimulus absence in rats
(Rattus norvegicus).
AB - Questions regarding the nature of nonhuman cognition continue to be of great
interest within cognitive science and biology. However, progress in
characterizing the relative contribution of "simple" associative and more
"complex" reasoning mechanisms has been painfully slow-something that the
tendency for researchers from different intellectual traditions to work
separately has only exacerbated. This article reexamines evidence that rats
respond differently to the nonpresentation of an event than they do if the
physical location of that event is covered. One class of explanation for the
sensitivity to different types of event absence is that rats' representations go
beyond their immediate sensory experience and that covering creates uncertainty
regarding the status of an event (thus impacting on the underlying causal model
of the relationship between events). A second class of explanation, which
includes associative mechanisms, assumes that rats represent only their direct
sensory experience and that particular features of the covering procedures
provide incidental cues that elicit the observed behaviors. We outline a set of
consensus predictions from these two classes of explanation focusing on the
potential importance of uncertainty about the presentation of an outcome. The
example of covering the food-magazine during the extinction of appetitive
conditioning is used as a test case for the derivation of diagnostic tests that
are not biased by preconceived assumptions about the nature of animal cognition.
(PsycINFO Database Record
PMID- 27512824
TI - Associative learning as higher order cognition: Learning in human and nonhuman
animals from the perspective of propositional theories and relational frame
theory.
AB - We aim to provide a new perspective on the old debate about whether evidence for
higher order cognition in nonhuman animals can be reinterpreted in terms of
associative learning. Our starting point is the idea that associative learning is
best thought of as an effect (i.e., the impact of paired events on behavior)
rather than a specific mental process (e.g., the formation of associations). This
idea allows us to consider (a) propositional theories according to which
associative learning is mediated by higher order mental processes akin to problem
solving and (b) relational frame theory that allows one to think of seemingly
simple associative learning effects as instances of a complex phenomenon known as
arbitrarily applicable relational responding. Based on these 2 theories, we argue
that (a) higher order cognition and associative learning are not necessarily
mutually exclusive and (b) a more sophisticated conceptualization of higher order
cognition is warranted. (PsycINFO Database Record
PMID- 27512825
TI - Causal reasoning versus associative learning: A useful dichotomy or a strawman
battle in comparative psychology?
AB - The debate about whether or not one could/should ascribe reasoning abilities to
animals has deep historical roots and seems very up-to-date in the light of the
immense body of new empirical data originating from various species and research
paradigms. Associative learning (AL) seems to be a ubiquitous low-level contender
for any cognitive interpretation of animal behavior, mostly because of the
assumed mechanistic simplicity and phylogenetic prevalence. However, the implicit
assumption that AL is simple and therefore the most parsimonious mechanism to
describe seemingly complex behavior can and must be questioned on various
grounds. Using recent empirical findings with chimpanzees as an example, I argue
that at times inferential reasoning might be the most likely candidate to account
for performance differences between experimental and control conditions. Finally,
a general conclusion drawn from the current debate(s) in the field of comparative
psychology could be that a dichotomist battle of 2 conceptual camps-each of which
is lacking a clear and homogeneous theoretical framework-is a scientific
deadlock. (PsycINFO Database Record
PMID- 27512826
TI - From Two to One Per Day Calibration of Dexcom G4 Platinum by a Time-Varying Day
Specific Bayesian Prior.
AB - BACKGROUND: In the DexCom G4 Platinum (DG4P) continuous glucose monitoring (CGM)
sensor, the raw current signal generated by glucose-oxidase is transformed to
glucose concentration by a calibration function whose parameters are periodically
updated by matching self-monitoring of blood glucose references, usually twice a
day, to compensate for sensor variability in time. The aim of this work is to
reduce DG4P calibration frequency to once a day by a recently proposed Bayesian
calibration algorithm, which employs a time-varying calibration function and
suitable day-specific priors. METHODS: The database consists of 57 CGM signals
that are collected by the DG4P for 7 days. The Bayesian calibration algorithm is
used to calibrate the raw current signal following two different schedules, that
is, two and one calibration per day. Calibrated glycemic profiles are compared
with those originally acquired by the manufacturer, on days 1, 4, and 7, where
frequent blood glucose references were available, by using standard metrics, that
is, mean absolute relative difference (MARD), percentage of accurate glucose
estimates, and percentage of data in the A-zone of Clarke Error Grid. RESULTS:
The one per day Bayesian calibration algorithm has accuracy similar to that of
two per day (11.8% vs. 11.7% MARD, respectively), and it is statistically better
(P-value of 0.0411) than the manufacturer calibration algorithm, which requires
two calibrations per day (13.1% MARD). CONCLUSIONS: A Bayesian calibration
algorithm employing a time-varying calibration function and suitable priors
enables a reduction of the calibrations of DG4P sensor from two to one per day.
PMID- 27512827
TI - A Phytosterol-Enriched Spread Improves Lipid Profile and Insulin Resistance of
Women with Gestational Diabetes Mellitus: A Randomized, Placebo-Controlled Double
Blind Clinical Trial.
AB - BACKGROUND: Gestational diabetes mellitus (GDM) has become a serious health risk
among pregnant women throughout the world. Phytosterol-enriched margarines are
capable of lowering total cholesterol (TC) and low-density lipoprotein (LDL), but
little is known about its effects on GDM. We aimed to examine the effects of
daily consumption of a phytosterol-enriched spread on insulin resistance and
lipid profile in pregnant GDM women. METHODS: Pregnant women suffering from GDM
in their second trimester were recruited and randomly assigned to consume a
margarine spread either with or without phytosterols daily for 16 weeks. Serum
lipid profile and glucose and insulin metabolisms were assessed at week 0
(baseline) and week 16 (end of trial). RESULTS: After 16 weeks, levels of
triacylglycerol, TC, and LDL were significantly decreased, while high-density
lipoprotein was significantly increased, compared with the baseline in the
phytosterol group. In addition, in the same treatment group, glucose metabolic
parameters, including fasting plasma glucose, serum insulin levels, the
quantitative insulin check index, homeostasis model of assessment of insulin
resistance, and beta-cell function, were also significantly improved. CONCLUSION:
Daily consumption of a phytosterol-enriched spread improved insulin resistance
and lipid profile in women with GDM.
PMID- 27512829
TI - In Ovo Sexing of Domestic Chicken Eggs by Raman Spectroscopy.
AB - Male birds of egg-laying hen strains have no commercial value and are culled
immediately after hatching, raising concerns for animal welfare. Existing
experimental methods for in ovo sexing require taking samples and are applicable
after embryos' sexual differentiation. We demonstrate that Raman spectroscopy
enables contactless in ovo sex determination of the domestic chicken (Gallus
gallus f. dom.) already at day 3.5 of egg incubation. A sexing accuracy of 90%
was obtained by analyzing the spectra of blood circulating in the extraembryonic
vessels. The measurement is damage-free and barely affects the hatching rate. Sex
recognition is achieved before the onset of sensitivity. Therefore, Raman
spectroscopy provides an alternative to the culling of 1-day-old male chicks in
laying hen production.
PMID- 27512828
TI - An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host
Microbiome Axis.
AB - Medical responders to radiological and nuclear disasters currently lack
sufficient high-throughput and minimally invasive biodosimetry tools to assess
exposure and injury in the affected populations. For this reason, we have focused
on developing robust radiation exposure biomarkers in easily accessible biofluids
such as urine, serum and feces. While we have previously reported on urine and
serum biomarkers, here we assessed perturbations in the fecal metabolome
resulting from exposure to external X radiation in vivo. The gastrointestinal
(GI) system is of particular importance in radiation biodosimetry due to its
constant cell renewal and sensitivity to radiation-induced injury. While the
clinical GI symptoms such as pain, bloating, nausea, vomiting and diarrhea are
manifested after radiation exposure, no reliable bioindicator has been identified
for radiation-induced gastrointestinal injuries. To this end, we focused on
determining a fecal metabolomic signature in X-ray irradiated mice. There is
overwhelming evidence that the gut microbiota play an essential role in gut
homeostasis and overall health. Because the fecal metabolome is tightly
correlated with the composition and diversity of the microorganism in the gut, we
also performed fecal 16S rRNA sequencing analysis to determine the changes in the
microbial composition postirradiation. We used in-house bioinformatics tools to
integrate the 16S rRNA sequencing and metabolomic data, and to elucidate the gut
integrated ecosystem and its deviations from a stable host-microbiome state that
result from irradiation. The 16S rRNA sequencing results indicated that radiation
caused remarkable alterations of the microbiome in feces at the family level.
Increased abundance of common members of Lactobacillaceae and Staphylococcaceae
families, and decreased abundances of Lachnospiraceae, Ruminococcaceae and
Clostridiaceae families were found after 5 and 12 Gy irradiation. The metabolomic
data revealed statistically significant changes in the microbial-derived products
such as pipecolic acid, glutaconic acid, urobilinogen and homogentisic acid. In
addition, significant changes were detected in bile acids such as taurocholic
acid and 12-ketodeoxycholic acid. These changes may be associated with the
observed shifts in the abundance of intestinal microbes, such as R. gnavus ,
which can transform bile acids.
PMID- 27512830
TI - Unsymmetric (MU-oxido)/(MU-pyrazolato) and Symmetric (MU-pyrazolato)2 Bridged
Diosmium Frameworks: Electronic Structure and Magnetic Properties.
AB - The present article deals with the structurally characterized unsymmetric
oxido/pyrazolato-bridged [(bpy)2Os(III)(MU-oxido)(MU-pz)Os(III)(bpy)2](ClO4)3
([1](ClO4)3) and symmetric dipyrazolato-bridged [(bpy)2Os(II)(MU
pz)2Os(II)(bpy)2](ClO4)2 ([2](ClO4)2) (pz = pyrazolato, bpy = 2,2'-bipyridine)
complexes with the Os...Os separations of 3.484 and 4.172 A, respectively. The
anti-ferromagnetically coupled Os(III) centers [E(S = 1)-E(BS(1,1) S = 0) =
322.504 cm(-1)] in 1(3+) and diamagnetic (S = 0) 2(2+) exhibit well-resolved (1)H
NMR resonances. [1](ClO4)3 shows temperature- and magnetic field-dependent
paramagnetism at low magnetic field and diamagnetism at high magnetic field.
1(3+) and 2(2+) display successive metal-based oxidation processes involving the
intermediate mixed-valent states and isovalent congeners: Os(IV)Os(IV) (1(5+))
>Os(III)Os(IV) (1(4+))?Os(III)Os(III) (1(3+))?Os(III)Os(II) (1(2+)) and
Os(III)Os(III) (2(4+))->Os(II)Os(III) (2(3+))?Os(II)Os(II) (2(2+)) as well as bpy
centered reductions. The effect of pi donor O(2-) and sigma/pi-donating pz(-) in
1(3+) and 2(2+), respectively, leads to varying oxidation state of the metal ions
in the isolated complexes: Os(III)Os(III) versus Os(II)Os(II). UV-visible-near-IR
electron paramagnetic resonance spectro-electrochemistry and density functional
theory (DFT)/time-dependent DFT calculations collectively reveal overlapping of
the metal- and ligand (pz, O, bpy)-based frontier orbitals in the delocalized
mixed-valent states in 1(4+) and 1(2+) with comproportionation constant (Kc)
value > 1 * 10(14) as well as in isovalent 1(3+), resulting in mixed metal/ligand
to metal/ligand near-IR transitions in all the three states. The mixed-valent
Os(II)Os(III) state in 2(3+) exhibits high Kc value of 1 * 10(22) corresponding
to a strong electrochemical coupling situation. However, closeness of the
bandwidth (Deltanu1/2, 4861 cm(-1)) of broad and weak intervalence charge
transfer transition of 2(3+) at 1360 nm (epsilon/M(-1) cm(-1): 490) with the
calculated Deltanu1/2 of 4121 cm(-1) based on the Hush formula as well as spin
density distributions of Os1: 0.811/0.799, Os2: 0.045/0042, and pz: 0.162/0.173
in meso and rac diastereomeric forms, respectively, attribute its localized class
II state.
PMID- 27512831
TI - Design and Synthesis of Pyridone-Containing 3,4-Dihydroisoquinoline-1(2H)-ones as
a Novel Class of Enhancer of Zeste Homolog 2 (EZH2) Inhibitors.
AB - A new enhancer of zeste homolog 2 (EZH2) inhibitor series comprising a
substituted phenyl ring joined to a dimethylpyridone moiety via an amide linkage
has been designed. A preferential amide torsion that improved the binding
properties of the compounds was identified for this series via computational
analysis. Cyclization of the amide linker resulted in a six-membered lactam
analogue, compound 18. This transformation significantly improved the ligand
efficiency/potency of the cyclized compound relative to its acyclic analogue.
Additional optimization of the lactam-containing EZH2 inhibitors focused on
lipophilic efficiency (LipE) improvement, which provided compound 31. Compound 31
displayed improved LipE and on-target potency in both biochemical and cellular
readouts relative to compound 18. Inhibitor 31 also displayed robust in vivo
antitumor growth activity and dose-dependent de-repression of EZH2 target genes.
PMID- 27512834
TI - Solvation of N,C-Protected Valine: Interactions with DMSO and a Chiral Solvating
Agent.
AB - Small protected amino acids find applications in many fields of chemistry. Their
solvation, however, is often only studied in aqueous solution. In this
contribution, the solvent-dependent conformational preferences of N,C-protected
Boc-Val-NH-C3H7 are investigated by a combined VCD spectroscopic and theoretical
approach. Replica exchange molecular dynamics simulations at the PM6 level and
DFT calculations are both found to predict the conformational preferences in
chloroform very well, which is confirmed by comparison of experimental and
calculated IR and VCD spectra. In the case of DMSO, we find that solute-solvent
interactions have to be taken into account explicitly in the simulation of the
spectra. Furthermore, we show that the experimental spectra are better resembled
by considering the conformational distribution obtained from the REMD simulations
than from DFT. Finally, we also show that the weak interaction of Boc-Val-NH-C3H7
with a chiral solvating agent also induces a small VCD spectral signature.
PMID- 27512836
TI - Clinical features of Hispanic thyroid cancer cases and the role of known genetic
variants on disease risk.
AB - Thyroid cancer (TC) is the second most common cancer among Hispanic women. Recent
genome-wide association (GWA) and candidate studies identified 6 single
nucleotide polymorphisms (SNPs; rs966423, rs2439302, rs965513, rs6983267,
rs944289, and rs116909374), associated with increased TC risk in Europeans but
their effects on disease risk have not been comprehensively tested in Hispanics.
In this study, we aimed to describe the main clinicopathological manifestations
and to evaluate the effects of known SNPs on TC risk and on clinicopathological
manifestations in a Hispanic population.We analyzed 281 nonmedullary TC cases and
1146 cancer-free controls recruited in a multicenter population-based study in
Colombia. SNPs were genotyped by Kompetitive allele specific polymerase chain
reaction (KASP) technique. Association between genetic variants and TC risk was
assessed by computing odds ratios (OR) and confidence intervals (CIs).Consistent
with published data in U.S. Hispanics, our cases had a high prevalence of large
tumors (>2 cm, 43%) and a high female/male ratio (5:1). We detected significant
associations between TC risk and rs965513A (OR = 1.41), rs944289T (OR = 1.26),
rs116909374A (OR = 1.96), rs2439302G (OR = 1.19), and rs6983267G (OR = 1.18).
Cases carried more risk alleles than controls (5.16 vs. 4.78, P = 4.8 * 10).
Individuals with >=6 risk alleles had >6-fold increased TC risk (OR = 6.33, P =
4.0 * 10) compared to individuals with <=2 risk alleles. rs944289T and
rs116909374A were strongly associated with follicular histology (ORs = 1.61 and
3.33, respectively); rs2439302G with large tumors (OR = 1.50); and rs965513A with
regional disease (OR = 1.92).To our knowledge, this is the first study of known
TC risk variants in South American Hispanics and suggests that they increase TC
susceptibility in this population and can identify patients at higher risk of
severe disease.
PMID- 27512837
TI - 23-Gauge vitrectomy with external drainage therapy as a novel procedure to
displace massive submacular hemorrhage secondary to polypoidal choroidal
vasculopathy.
AB - INTRODUCTION: Massive subretinal hemorrhage (SRH) due to polypoidal choroidal
vasculopathy (PCV) remains a challenging field and the best treatment is still
not certain. In the present study, we performed a novel surgical method which
combined 23-gauge vitrectomy with external drainage therapy for displace massive
SRH secondary to PCV. METHODS: From April 2015 to July 2015, 4 consecutive
patients with massive SRH secondary to PCV received 23-gauge transconjunctival
sutureless vitrectomy with external drainage therapy. Massive SRH was drained by
scleral tunnel which was created using 30-gauge ultrathin needles during
vitrectomy. We assessed the feasibility and safety of this procedure by analyzing
best-corrected vision acuity (BCVA), central foveal thickness (CFT), and
complication. RESULTS: Four patients had a mean age of 63.8 +/- 6.4 years (range:
59-73 years). The average interval between onset of symptoms of SRH and surgery
was 23.8 +/- 11.1 days (range: 10-35 days). Mean follow-up duration was 7.0 +/-
0.8 months. All patients completed 6 months follow-up. Mean BCVA gradually
improved during the follow-up period. At 6 months after treatment, mean BCVA was
significantly improved in comparison to preoperative findings (P = 0.043, paired
t test). One month after treatment, mean CFT was significantly thinner than
baseline (P = 0.002, paired t test). No serious ocular or systemic adverse events
were observed to be associated with combination of 23-gauge vitrectomy with
external drainage therapy during the 6 months follow-up period. CONCLUSIONS: Our
results show that a combination of 23-gauge vitrectomy with external drainage
therapy is a novel effective and safe procedure that may be a good alternative
for massive SRH due to PCV.
PMID- 27512838
TI - Trastuzumab improves locoregional control in HER2-positive breast cancer patients
following adjuvant radiotherapy.
AB - The benefit of adjuvant trastuzumab in disease-free and overall survival for
human epidermal receptor 2-positive (HER2+) breast cancer patients is well
established. However, the effect of trastuzumab on locoregional control remains
unclear, particularly in patients treated with adjuvant radiotherapy (RT). In
this study, we investigated the locoregional benefit of trastuzumab in patients
with HER2+ breast cancer after adjuvant RT.Using a single institutional database,
we identified 278 patients with stage II/III invasive HER2+ breast tumors
receiving adjuvant RT between January 2008 and July 2011. We compared the
locoregional outcomes of 134 patients who received trastuzumab to 144 patients
without trastuzumab within the same period. Clinical and biological factors that
might impact on the locoregional benefit of trastuzumab were also assessed.At the
median follow-up of 45 months, trastuzumab significantly lowered the risk of
locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the
cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with
a more significant locoregional benefit in the hormone receptor-positive
(HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and
without trastuzumab (P = 0.027). For HR-/HER2+ breast tumor patients, the 3-year
LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However,
statistical significance was not found (P = 0.179). Both univariate and
multivariate analyses confirmed that trastuzumab treatment was the only
significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence
interval, 1.07-15.35; P = 0.039).Adjuvant trastuzumab in addition to RT is
associated with significant reduced LRR risk in HER2+ breast cancer.
PMID- 27512839
TI - Analysis of 4000 kidney transplantations in a single center: Across immunological
barriers.
AB - Kidney transplant (KT) is the optimal renal replacement therapy for patients with
end-stage renal disease (ESRD). The demand for kidneys, however, continues to
exceed the supply. To overcome this problem, efforts to extend the donor pool by
including human leukocyte antigen (HLA)- and ABO-incompatible (ABOi) KTs are
increasing. The aim of this article was to retrospectively review data on
recipients, donor profiles, and clinical outcomes in 4000 cases of KT. In
addition, we analyzed clinical outcomes in ABOi and flow-cytometric crossmatch
(FCXM) positive KT in a subgroup analysis.This was a retrospective, observational
study using data extracted from medical records. A total of 4000 consecutive
patients who underwent KT at our institution from January 1990 to February 2015
were included in this study. KTs across immunological barriers such as ABO
incompatible (276 cases, 6.9%), FCXM positive (97 cases, 2.4%), and positive
complement-dependent cytotoxicity (CDC) XM KT (16 cases, 0.4%) were included.From
a Kaplan-Meier analysis, overall patient survival (PS) rates after KT at 1, 5,
10, and 20 years were 96.9%, 95.1%, 92.0%, and 88.9%, respectively. The overall
graft survival (GS) rates after KT at 1, 5, 10, and 20 years were 96.3%, 88.9%,
81.2%, and 67.4%, respectively. Our subgroup analysis suggested that overall PS,
GS, death-censored GS, and rejection-free GS in ABOi KT showed no significant
differences in comparison with ABO-compatible KT if adequate immunosuppressive
treatment was performed. The overall PS rate in patients who underwent FCXM
positive KT did not differ significantly from that of the control group during
the 3-year follow-up (P = 0.34). The overall GS, death-censored GS, and rejection
free GS also did not differ significantly between the FCXM KT and control groups
(P = 0.99, 0.42, and 88).The outcomes of KTs continually improved during the
study period, while the annual number of KTs increased. ABO or FCXM positive KTs
can be performed safely with successful graft outcomes.
PMID- 27512840
TI - Relation between primary tumor FDG avidity and site of first distant metastasis
in patients with breast cancer.
AB - Identification of tumor imaging features associated with metastatic pattern may
allow better understanding of cancer dissemination. Here, we investigated how
primary tumor F-fluorodeoxyglucose (FDG) avidity influences the first site of
breast cancer metastasis.Subjects were 264 patients with advanced breast cancer
who underwent positron emission tomography/computed tomography at diagnosis and
had metastasis at presentation (n = 193) or metastatic relapse after surgery (n =
71). Primary tumor FDG avidity (maximum SUV [SUVmax] >=10.1) was compared with
histology and first metastatic sites.The most common site of first metastasis was
the bone, occurring in 62.7% of patients with metastasis at presentation and
38.0% of those with metastatic relapse. First metastasis to lung occurred in
30.1% and 35.2%, and to liver in 25.4% and 15.2% of respective groups. In
patients with metastasis at presentation, primary tumors were FDG avid in 98/193
cases, and this was associated with more frequent first metastasis to lung (37.8%
vs 22.1%; P = 0.018). In patients with metastasis relapse, primary tumors were
FDG avid in 31/71 cases, and this was associated with more frequent first
metastasis to lung (48.4% vs 25.0%; P = 0.041) and liver (29.0% vs 5.0%; P =
0.008). In patients with metastasis relapse, primary tumors that were FDG avid
but hormone receptor negative had more first metastasis to lung (57.9% vs 26.9%;
P = 0.016).FDG-avid primary breast tumors have favored first spread to the lung
and liver, which suggests that tumor cells with heightened glycolytic activity
better colonize these organs.
PMID- 27512841
TI - The diagnostic value of 1.5-T diffusion-weighted MR imaging in detecting 5 to 10
mm metastatic cervical lymph nodes of nasopharyngeal carcinoma.
AB - The aim of the study was to prospectively assess the diagnostic accuracy of 1.5 T
diffusion-weighted imaging (DWI) for 5 to 10 mm metastatic cervical lymph nodes
of patients with nasopharyngeal carcinoma (NPC). All patients with
histopathologically confirmed NPC underwent DWI with 2 b values of 0 and 800 s/mm
were enrolled. The shortest axial diameter and mean apparent diffusion
coefficient (ADC) value were recorded when lymph nodes with a shortest axial
diameter from 5 to 10 mm were measured. The correlation between the pathological
diagnoses and mean ADC values in the benign and metastatic lymph nodes were
compared using the Z test. Receiver operating characteristic (ROC) curve analysis
was performed to evaluate the diagnostic performance of DWI. Three hundred
fourteen nodes of 52 patients with NPC consisted of 46.5% (146/314) metastatic
lymph nodes and 53.5% (168/314) benign lymph nodes. The mean ADC value (*10 mm/s)
of benign lymph nodes was (1.110 +/- 0.202), which was significantly higher than
that of metastatic nodes (0.878 +/- 0.159) (P < 0.05). The sensitivity,
specificity, positive predictive value, and negative predictive value, accuracy
for differentiating metastatic from benign lymph nodes using a cutoff ADC value
of 0.924 * 10 mm/s was 83.56%, 82.74%, 80.79%, 85.28%, and 82.80%, respectively.
The area under the ROC curve was 0.851 (95% confidence intervals: 0.807-0.889).
This study demonstrated that DWI is helpful in detecting 5 to 10 mm metastatic
lymph nodes of patients with NPC.
PMID- 27512842
TI - Association between peroxisome proliferator-activated receptor-alpha, delta, and
gamma polymorphisms and risk of coronary heart disease: A case-control study and
meta-analysis.
AB - OBJECTIVES: Risk of coronary heart disease (CHD) has been suggested to be
associated with polymorphisms of peroxisome proliferator-activated receptors
(PPARs), while the results were controversial. We aimed to systematically assess
the association between PPAR polymorphisms and CHD risk. METHODS: A case-control
study with 446 subjects was conducted to evaluate the association between CHD
risk and C161T polymorphism, which was of our special interest as this
polymorphism showed different effects on risks of CHD and acute coronary syndrome
(ACS). Meta-analyses were conducted to assess all PPAR polymorphisms. Either a
fixed- or a random-effects model was adopted to estimate overall odds ratios
(ORs). RESULTS: In the case-control study, T allele carriers of C161T
polymorphism were not significantly associated with CHD risk (Odds ratio (OR) =
0.74, 95% confidence interval (CI) 0.47-1.15, P = 0.19), while T allele carriers
showed higher risk of ACS (OR = 1.63, 95% CI 1.00-2.65, P = 0.048). The meta
analysis indicated that compared with CC homozygous, T allele carriers had lower
CHD risk (OR = 0.69, 95% CI 0.59-0.82, P < 0.001) but higher ACS risk (OR = 1.43,
95% CI 1.09-1.87, P = 0.010). Three other polymorphisms were also found to be
significantly associated with CHD risk under dominant model: PPAR-alpha intron
7G/C polymorphism (CC+GC vs GG, OR 1.42, 95% CI 1.13-1.78, P = 0.003), L162V
polymorphism (VV+LV vs LL, OR 0.74, 95% CI 0.56-0.97, P = 0.031), and PPAR-delta
+294T/C polymorphism (CC+TC vs TT, OR 1.51, 95% CI 1.12-2.05, P = 0.007).
CONCLUSIONS: The results suggested that PPAR-alpha intron 7G/C and L162V, PPAR
delta +294T/C and PPAR-gamma C161T polymorphisms could affect CHD susceptibility,
and C161T polymorphism might have different effects on CHD and ACS.
PMID- 27512843
TI - Change in refraction after lens-sparing vitrectomy for rhegmatogenous retinal
detachment and epiretinal membrane.
AB - The aim of this study was to compare changes in refraction following lens-sparing
vitrectomy between patients with rhegmatogenous retinal detachment (RRD) and
epiretinal membrane (ERM) and to investigate factors associated with the change
in refraction.We reviewed medical records of 49 eyes of 49 patients with RRD
(53.6 +/- 7.8 years, mean +/- standard deviation) and 24 eyes of 24 patients with
ERM (50.9 +/- 15.7 years) who underwent lens-sparing vitrectomy. Spherical
equivalent refractive power was evaluated before and up to 18 months after
surgery. The relationship between the change in refraction and several parameters
was evaluated.A significant progressive myopic shift in refractive power was
observed after vitrectomy in operated RRD and ERM eyes (P < 0.001, P = 0.016,
respectively), with no significant difference in fellow eyes. The refraction
values observed at >=3 and >=12 months following vitrectomy were significantly
different as compared with those observed at baseline in the RRD group (P <
0.001) and the ERM group (P < 0.05), respectively. The change in refraction
between the RRD and ERM groups was significant (P = 0.030). The multiple linear
regression analysis showed that only age was significantly correlated with the
change in refraction in RRD (P = 0.018) and ERM (P < 0.001) groups. The change in
refraction was significantly and positively correlated with age in RRD (r =
0.461, P = 0.001) and ERM (r = -0.687, P < 0.001) groups. Following lens-sparing
vitrectomy, cataract surgery was performed on 30 eyes after 0.89 +/- 0.26 years
in the RRD group and on 10 eyes after 1.11 +/- 0.14 years in the ERM group; there
was a significant difference in time to cataract surgery between the groups (P =
0.007). Kaplan-Meier survival analysis demonstrated that there was a significant
difference in the rate of cataract surgeries between the RRD and ERM groups (P =
0.022).Following lens-sparing vitrectomy for RRD and ERM, a progressive myopic
shift in refraction owing to nuclear sclerosis was observed. Core vitrectomy
itself would cause a myopic shift of refraction. The only risk factor associated
with cataract progression following lens-sparing vitrectomy is age for both types
of patients.
PMID- 27512844
TI - Association between body mass index and mortality in a prospective cohort of
Chinese adults.
AB - Obesity is associated with an increased risk of diabetes mellitus, hypertension,
and coronary artery disease; however, the relation between body mass index (BMI)
and the risk of all-cause mortality is controversial. We prospectively examined
the relationship between BMI and all-cause mortality in 123,384 Chinese men and
women who participated in the Kailuan health examination study from 2006 to 2007
and 2008 to 2009. Cases included 6218 deaths (5770 men and 448 women) that
occurred during a mean follow-up period of 7.39 years. Relative risk was adjusted
for factors such as age, serum lipid levels (ie, triglyceride, high-density
lipoprotein, and low-density lipoprotein cholesterol), history of smoking and
drinking, and physical activity, as well as a medical history of hypertension,
diabetes, myocardial infarction, and stroke. Within the cohort, the lowest risk
of all-cause mortality was seen among persons with a BMI of 24 to 28 kg/m in
male, and the risk was elevated among persons with BMI levels lower or higher
than that range. Moreover, all-cause mortality was greatest in the group with a
BMI of <18.5 kg/m. In contrast, in female, a high BMI was associated with
increased mortality, and a BMI of <18.5 kg/m was associated with the lowest risk.
Further, a U-shaped association was seen between BMI and the risk of death from
any cause among men and women, even after adjusting for confounding factors. In
conclusion, underweight was associated with a substantially increased risk of all
cause mortality in males. The excess risk of all-cause mortality with a high BMI,
however, was seen among females.
PMID- 27512845
TI - Significant contribution of subtype G to HIV-1 genetic complexity in Nigeria
identified by a newly developed subtyping assay specific for subtype G and
CRF02_AG.
AB - While abundant sequence information is available from human immunodeficiency
virus type 1 (HIV-1) subtypes A, B, C and CRF01_AE for HIV-1 vaccine design,
sequences from West Africa are less represented. We sought to augment our
understanding of HIV-1 variants circulating in 6 Nigerian cities as a step to
subsequent HIV-1 vaccine development.The G/CRF02_AG multi-region hybridization
assay (MHA) was developed to differentiate subtype G, CRF02_AG and their
recombinants from other subtypes based on 7 HIV-1 segments. Plasma from 224 HIV-1
infected volunteers enrolled in a cohort examining HIV-1 prevalence, risk factor,
and subtype from Makurdi (30), Abuja (18), Enugu (11), Kaduna (12), Tafa (95),
and Ojo/Lagos (58) was analyzed using MHA. HIV-1 genomes from 42 samples were
sequenced to validate the MHA and fully explore the recombinant structure of G
and CRF02_AG variants.The sensitivity and specificity of MHA varied between 73
100% and 90-100%, respectively. The subtype distribution as identified by MHA
among 224 samples revealed 38% CRF02_AG, 28% G, and 26% G/CRF02_AG recombinants
while 8% remained nontypeable strains. In envelope (env) gp120, 38.84% of the
samples reacted to a G probe while 31.25% reacted to a CRF02 (subtype A) probe.
Full genome characterization of 42 sequences revealed the complexity of Nigerian
HIV-1 variants.CRF02_AG, subtype G, and their recombinants were the major
circulating HIV-1 variants in 6 Nigerian cities. High proportions of samples
reacted to a G probe in env gp120 confirms that subtype G infections are abundant
and should be considered in strategies for global HIV-1 vaccine development.
PMID- 27512846
TI - CBCT-based 3D MRA and angiographic image fusion and MRA image navigation for
neuro interventions.
AB - Digital subtracted angiography (DSA) remains the gold standard for diagnosis of
cerebral vascular diseases and provides intraprocedural guidance. This practice
involves extensive usage of x-ray and iodinated contrast medium, which can induce
side effects. In this study, we examined the accuracy of 3-dimensional (3D)
registration of magnetic resonance angiography (MRA) and DSA imaging for cerebral
vessels, and tested the feasibility of using preprocedural MRA for real-time
guidance during endovascular procedures.Twenty-three patients with suspected
intracranial arterial lesions were enrolled. The contrast medium-enhanced 3D DSA
of target vessels were acquired in 19 patients during endovascular procedures,
and the images were registered with preprocedural MRA for fusion accuracy
evaluation. Low-dose noncontrasted 3D angiography of the skull was performed in
the other 4 patients, and registered with the MRA. The MRA was overlaid
afterwards with 2D live fluoroscopy to guide endovascular procedures.The 3D
registration of the MRA and angiography demonstrated a high accuracy for vessel
lesion visualization in all 19 patients examined. Moreover, MRA of the
intracranial vessels, registered to the noncontrasted 3D angiography in the 4
patients, provided real-time 3D roadmap to successfully guide the endovascular
procedures. Radiation dose to patients and contrast medium usage were shown to be
significantly reduced.Three-dimensional MRA and angiography fusion can accurately
generate cerebral vasculature images to guide endovascular procedures. The use of
the fusion technology could enhance clinical workflow while minimizing contrast
medium usage and radiation dose, and hence lowering procedure risks and
increasing treatment safety.
PMID- 27512847
TI - Microflow imaging of contrast-enhanced ultrasound for evaluation of
neovascularization in peripheral lung cancer.
AB - The aim of this study was to investigate the role of microflow imaging (MFI) of
contrast-enhanced ultrasound (CEUS) for evaluating microvascular architecture of
different types of peripheral lung cancer (PLC) and to explore the correlated
pathological basis.Ninety-five patients with PLC were enrolled in this study. Two
radiologists independently evaluated the microvascular architecture of PLC with
MFI. The interobserver agreement was measured with Kappa test. The diagnosis
value of MFI was calculated. With pathological analysis, the correlation between
MFI and microvascular density (MVD)/microvascular diameter (MD) was evaluated.Of
the 95 PLCs, MFI were mainly classified "dead wood" (27.4%, 25.3%), "vascular"
(47.4%, 49.5%), and "cotton" (20.0%, 20.0%) patterns by the 2 readers. Kappa test
showed a good agreement between the 2 readers (Kappa = 0.758). The "dead wood"
can be regarded as a specific diagnostic factor for squamous carcinoma; the
sensitivity, specificity, and accuracy was 62.9%, 93.3%, and 82.1%, respectively.
The "vascular" and "cotton" patterns correlated well with adenocarcinoma and SCLC
(small cell lung cancer); diagnostic sensitivity, specificity, and accuracy were
86.7%, 65.7%, and 78.9%, respectively. MVD of "dead wood" was lower than
"vascular" and "cotton," while MD was bigger than the other 2 patterns (P <
0.05). There was a good correlation between MFI and histopathological types of
PLC as well as between MFI and MVD/MD (P < 0.05).MFI has the advantage to display
the microvascular architecture of PLCs and might become a promising diagnostic
method of histopathological types of PLC. MFI features also correlated well with
its pathological basis, including MVD and MD.
PMID- 27512848
TI - Delayed traumatic diaphragmatic hernia: A case-series report and literature
review.
AB - BACKGROUND: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to
identify at an early stage and can consequently result in diagnostic delays with
life-threatening outcomes. It is the aim of this case study to highlight the
difficulties encountered with the earlier detection of traumatic diaphragmatic
hernias. METHODS: Clinical data of patients who received treatment for delayed
traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of
Xi'an Jiaotong University from 1998 to 2014 were analyzed retrospectively.
RESULTS: Six patients were included in this study. Left hemidiaphragm was
affected in all of them. Most of the patients had a history of traffic accident
and 1 a stab-penetrating injury. The interval from injury to developing symptoms
ranged from 2 to 11 years (median 5 years). The hernial contents included the
stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in
all of them during the initial managements. All patients received operations once
the diagnosis of delayed TDH was confirmed, and no postoperative mortality was
detected. CONCLUSIONS: Delayed TDHs are not common, but can lead to serious
consequences once occurred. Early detection of diaphragmatic injuries is crucial.
Surgeons should maintain a high suspicion for injuries of the diaphragm in cases
with abdominal or lower chest traumas, especially in the initial surgical
explorations. We emphasize the need for radiographical follow-up to detect
diaphragmatic injuries at an earlier stage.
PMID- 27512849
TI - Peripheral platelet/lymphocyte ratio predicts lymph node metastasis and acts as a
superior prognostic factor for cervical cancer when combined with neutrophil:
Lymphocyte.
AB - Inflammation-based indicators such as neutrophil/lymphocyte ratio (NLR), derived
NLR (dNLR), and platelet/lymphocyte ratio (PLR) have been reported to possess
significant predictive value for several types of cancer. We investigated the
predictive value of these 3 biomarkers on lymph node metastasis (LNM) and
clinical outcome in patients with stage Ib1-IIa cervical cancer undergoing
radical surgery.A total of 407 patients with FIGO stage Ib1-IIa cervical cancer,
who underwent radical surgery between January 2006 and December 2009 at the
Department of Gynecological and Oncology of Shandong Cancer Hospital Affiliated
to Shandong University were recruited. Binary logistic regression analysis was
performed to determine the relationship between PLR, NLR, dNLR, and LNM.
Multivariate Cox regression analysis was performed to determine the association
between the 3 indices and recurrence-free survival (RFS) and overall survival
(OS).Optimal cut-off values for the 3 indices were determined by applying
receiver operating curve (ROC) analysis. Univariate and binary logistic
regression analyses both indicate that PLR was significantly associated with
increased LNM (P < 0.05). In the multivariate survival analysis, increased
preoperative PLR and NLR were significantly associated with reduced RFS (P =
0.001 and P = 0.002, respectively), whereas a combination of both PLR and NLR
revealed a more significant association with reduced RFS (P < 0.001).
Furthermore, increased preoperative PLR and NLR were significantly associated
with reduced OS (P = 0.007 and P = 0.009, respectively), whereas the combined use
of PLR and NLR revealed a more significant association with reduced OS (P =
0.003).PLR is an independent risk factor for increased LNM and clinical outcome
in patients with stage Ib1-IIa cervical cancer. A combination of PLR and NLR may
enable better risk stratification for predicting survival.
PMID- 27512850
TI - Increased TRPV1 and PAR2 mRNA expression levels are associated only with the
esophageal reflux symptoms, but not with the extraesophageal reflux symptoms.
AB - Transient receptor potential vanilloid-1 (TRPV1) receptor and proteinase
activated receptor 2 (PAR2) have been implicated in the mechanism of acid-induced
inflammation in gastroesophageal reflux disease (GERD). We aimed to evaluate
TRPV1 and PAR2 mRNA expression levels in the GERD patients and their relationship
with endoscopic findings and reflux symptoms.Sixteen healthy controls, 45
patients with erosive reflux disease (ERD), and 14 nonerosive reflux disease
(NERD) patients received endoscopy and completed questionnaires. Quantitative
real-time polymerase chain reactions (qPCR) of TRPV1, glial cell line-derived
neurotrophic factor (GDNF), nerve growth factor (NGF), PAR2, and interleukin (IL)
8 were performed in the distal esophagus specimen.The levels of TRPV1, GDNF, NGF,
PAR2, and IL-8 mRNA expression were highest in the ERD group followed by NERD and
control groups and the differences between control and ERD groups were
statistically significant. Within the ERD group, patients with grade B in Los
Angeles (LA) classification showed significantly higher levels of TRPV1, GDNF,
and NGF mRNA expression than those with grade A. Presence of reflux symptoms was
associated with significant higher levels of TRPV1, PAR2, and IL-8. Notably not
extraesophageal but esophageal reflux symptoms were significantly associated with
them.Upregulation of TRPV1 and PAR2 pathways might play a role in the development
of distal esophageal inflammation and reflux symptoms. And extraesophageal reflux
symptoms might not be associated with these processes.
PMID- 27512851
TI - Body mass index and waist-to-height ratio among schoolchildren with visual
impairment: A cross-sectional study.
AB - Children and adolescents with visual impairments may be predisposed to excessive
body mass due to restrictions in everyday functioning and the ability to take
part in physical activity. This study aimed to estimate the prevalence of
obesity, overweight, and abdominal obesity (AO) among blind and partially sighted
schoolchildren and to determine whether sociodemographic factors and
participation in physical education classes (PEC) are associated with excessive
body weight or AO in this group.A cross-sectional sample of 141 partially sighted
or blind schoolchildren aged 7 to 18.9 years were included in this study.
Anthropometric measurements were performed, and sociodemographic variables and
ability to attend PEC were recorded. Overweight and obesity were noted among
21.3% and 14.9% of students, respectively. Although more males than females had
excessive body weight (39.2% vs 32.3%), the difference was not significant (chi
square test [ch] = 3.197; probability value [P] = 0.362). There was a significant
association between mean body mass index standard deviation score and age
(results of ANOVA analysis [F] = 5.620; P = 0.0045). A waist-to-height ratio
(WHtR) >=0.50 was observed among 27.7% of pupils. The prevalence of AO in boys
and girls was 32.9% and 21.0%, respectively; this difference was not significant
(ch = 2.48; P = 0.12). There was a significant relationship between mean WHtR and
age (7-9 years: 0.477 +/- 0.050; 10-13 years: 0.484 +/- 0.065; >=14 years: 0.454
+/- 0.061; results of Kruskal-Wallis test [H] = 8.729; P = 0.023,
respectively).Multivariate logistic regression analysis showed that none of the
sociodemographic variables examined (except "having siblings") were significantly
associated with the occurrence of overweight, obesity, and AO. Subjects with no
siblings were 4 times more likely to have WHtR >= 0.5 (odds ratio [OR] = 4.22;
95% confidence interval [CI] = 1.33-17.8; P = 0.01).Overweight and obesity were
almost 4 times more frequent (OR = 3.74; 95% CI 0.81-17.4) and AO 3 times more
frequent (OR = 3.18, 95% CI 0.71-14.2) among students not participating in PEC.
Excessive body mass and AO represent an urgent health problem among
schoolchildren with visual impairments. Health education concerning healthy
eating habits and physical activity should be provided to this group to reduce
potential future health costs.
PMID- 27512852
TI - Pemetrexed/cisplatin as first-line chemotherapy for advanced lung cancer with
brain metastases: A case report and literature review.
AB - BACKGROUND: Brain metastases (BMs) are a common and serious complication of non
small cell lung cancer (NSCLC). Whole-brain radiotherapy (WBRT), surgery, and
molecular targeted therapy are usually used to treat NSCLC with BM.
Chemotherapeutic options for BM are limited by tumor resistance, ineffective
agents, and the blood-brain barrier. Pemetrexed/cisplatin is the preferred
chemotherapy in nonsquamous NSCLC, but the efficacy of this treatment for
nonsquamous NSCLC with BM is uncertain. METHODS: We present a case of nonsquamous
NSCLC with asymptomatic BM presenting with irritating cough and right shoulder
back pain (unknown sensitizing epidermal growth factor receptor mutations or
anaplastic lymphoma kinase). RESULTS: He benefited from administration of first
line chemotherapy of pemetrexed/cisplatin. Partial remission was achieved in the
primary lesion of the lungs and BM lesion. He was further given 3 cycles of
pemetrexed monotherapy and WBRT. Complete remission was further achieved in BM
lesion. CONCLUSION: The findings of clinical trials and theoretical studies about
the current pemetrexed/cisplatin in the treatment of nonsquamous NSCLC with BM
are also summarized to provide a reference for the application of
pemetrexed/cisplatin in nonsquamous NSCLC with BM. Whether or not
pemetrexed/cisplatin is definitely effective in nonsquamous NSCLC with BM must be
proven by subsequent phase III clinical trials.
PMID- 27512853
TI - Physiotherapists working in clinics have increased risk for new-onset spine
disorders: a 12-year population-based study.
AB - Health care professionals are known to have a high risk for work-related
musculoskeletal disorders. However, the information on the risk of new-onset
spine-related musculoskeletal disorders (SRMDs) in health care professionals is
insufficient. This study aimed to investigate new-onset spine disorder
associations among physical, occupational, and pharmacy health care professionals
working in different workplaces.Taiwan's National Health Insurance Research
Database for registered medical personnel claims from 2000 to 2011 was analyzed.
An age- and sex-matched longitudinal cohort study of 7448 subjects (1682
physiotherapists, 1682 occupational therapists [OTs], and 3724 pharmacists) with
or without new-onset spine disorders was conducted. The hazard ratios for the
development of new-onset spine disorders were estimated among these 3 groups.The
overall percentage of new-onset SRMD for physiotherapists is 32.12. The median
time from obtaining a registered license to developing SRMD is 1.94 years. The
log-rank test showed that physiotherapists have the least possibility of having a
SRMD-free rate (P < 0.0001). The Cox model showed that physiotherapists have a
higher risk of new-onset SRMD (hazard ratio: 1.65, 95% confidence interval: 1.48
1.84, P < 0.0001) compared with OTs and pharmacists. Physiotherapists working in
clinics have a 2.40-fold increased risk of developing SRMD (95% confidence
interval: 1.97-2.92, P < 0.0001) relative to OTs and pharmacists.This may be the
first study regarding new-onset SRMD in physiotherapists based on a powerful
nationwide population-based database. We conclude that working in clinics is a
potential risk for new-onset SRMD in physiotherapists. Therefore, we suggest that
physiotherapists should pay more attention to this issue to prevent the
development of spine disorders.
PMID- 27512854
TI - Socioeconomic inequities and cardiovascular disease-related disability in China:
A population-based study.
AB - The prevalence of disability has changed along with aggressive economic
development in China. However, socioeconomic inequalities associated with
cardiovascular disease (CVD)-related disability have not been explored. This is
the first study to explore CVD-related disability among persons aged 45 years and
older in China.Data were taken from the 2006 Second China National Sample Survey
on Disability, which was a nationally representative, population-based survey. To
derive a nationally representative sample, the survey used multistage,
stratified, and cluster random sampling with probability proportional to size. We
used standard weighting procedures to construct sample weights that considered
the multistage, stratified, and cluster sampling survey scheme. Associations
between CVD-related disability risk and socioeconomic inequality were examined
using logistic regression.In this study, the weighted prevalence of CVD-related
disability was 1.84 per 100 persons (95% confidence interval [CI]: 1.80-1.89),
and 73% of CVD-related disability consisted of a single disability, including
speech, physical, and intellectual disabilities, whereas 23% of CVD-related
disability consisted of multiple disabilities, that is, any combination of
speech, physical, and intellectual disabilities. A higher risk of CVD-related
disability was observed among rural residents than urban residents as well as
among males than females. Age presented consistent increased associations with
CVD-related disability. Education inequality was strongly associated with the
risk of multiple disabilities.To address the challenge of CVD-related disability
in China, the government should adjust its strategies for health care systems to
prevent disability. The widening discrepancy between urban and rural areas
indicates that the most important priorities for disability prevention in China
are to reinforce health promotion in the working age population and to improve
health services in rural communities.
PMID- 27512855
TI - Surgical treatment of double primary liver cancer: An observational study for a
rare type of tumor.
AB - Double primary liver cancer (DPLC) is a special type of clinical situation. As
such, a detailed analysis of the surgical management and prognosis of patients
with DPLC is lacking. The objective of the current study was to define the
management and outcome of patients undergoing surgery for DPLC at a major
hepatobiliary center.A total of 87 patients treated by surgical resection at the
Eastern Hepatobiliary Surgery Hospital from January 1st, 2007 to October 31st,
2013 who had DPLC demonstrated by final pathological diagnosis were identified.
Among these, 50 patients had complete clinical and prognostic data. Demographic
and tumor characteristics as well as the prognosis were analyzed.The proportion
of hepatitis B surface antigen (HBsAg) (+) and hepatitis B virus e antigen
(HBeAg) (+), HBsAg (+), and HBeAg (-) hepatocirrhosis in all patients was 21.84%,
67.82%, and 63.22%, respectively. Incidental findings accounted for 58.62% of
patients; among those who had symptoms, the main symptom was abdominal pain
(31.03%). Nonanatomic wedge resection was the main operative approach (62.07%).
Postoperatively, the main complications included seroperitoneum (11.49%),
hypoproteinemia (10.34%), and pleural effusion (8.05%). Factors associated with
disease-free survival (DFS) included intrahepatic cholangiocarcinoma (ICC) tumor
size (P = 0.002) and use of postoperative prophylactic transcatheter arterial
chemoembolization (TACE) treatment (P = 0.015). Meanwhile, hepatocellular
carcinoma (HCC) size (P = 0.045), ICC size (P < 0.001), and liver function
(including aspartate aminotransferase [P = 0.001] and r-glutamyl transferase [P <
0.001]) were associated with overall survival (OS).Hepatitis B virus (HBV)
related hepatitis or cirrhosis is also an important factor in the pathogenesis of
DPLC and surgical treatment is safe for it with low complication rates. In
addition, it is effective to prolong DFS that DPLC patients undergo postoperative
prophylactic TACE treatment.
PMID- 27512856
TI - Physical activity to overcome the adversity of widowhood: Benefits beyond
physical health.
AB - Widowhood has been increasingly encountered because of increasing longevity of
women, often characterized by social stigmatization and poor physical and mental
health. However, applied research to overcome its adversity has been quite
limited. The goal of this study is to explore the role of physical activity in
improving the health of widows.A cohort of 446,582 adults in Taiwan who
successively participated in a comprehensive medical screening program starting
in 1994, including 232,788 women, was followed up for mortality until 2008. Each
individual provided detailed health history, and extensive lab tests results.The
number of widows increased with time trend. Every other woman above age 65 was a
widow (44%). Widows were less active, more obese, and smoked and drank more, had
sleep problems, were more depressed with taking sedatives or psychoactive drugs,
leading to more suicides. In the global development of health policies by World
Health Organization (WHO), physical activity is one of the main factors to
reverse poor health. The poor health of inactive widow was mitigated when
becoming fully active in this study. Exercise not only reduced the observed 18%
increase in all-cause mortality, but also gained 4 years and as much as 14%
mortality advantage over the married but inactive. More importantly, becoming
physically active energized their mental status, improved sleep quality and
quantity, reduced depressions and the need for psychoactive drugs, and increased
socialization circles.Widows, a rapidly growing and socially stigmatized group,
suffered from social and financial inequality and tended to develop poorer
health. Sustained physical activity could be one of the ways for them to overcome
and reverse some of the physical and mental adversities of widowhood, and improve
their quality and quantity of life.
PMID- 27512857
TI - Tissue expander placement and adjuvant radiotherapy after surgical resection of
retroperitoneal liposarcoma offers improved local control.
AB - Given that retroperitoneal liposarcoma (LPS) is extremely difficult to completely
resect, and has a relatively high rate of recurrence, radiotherapy (RT) is the
treatment of choice after surgical resection. However, it is difficult to obtain
a sufficient radiation field because of the close proximity of surrounding
organs. We introduce the use of tissue expanders (TEs) after LPS resection in an
attempt to secure a sufficient radiation field and to improve recurrence-free
survival.This study is a retrospective review of 53 patients who underwent
surgical resection of LPS at Samsung Medical Center between January 1, 2005, and
December 31, 2012, and had no residual tumor detected 2 months postoperatively.
The median follow-up period was 38.9 months.Patients were divided into 3 groups.
Those in group 1 (n = 17) had TE inserted and received postoperative RT. The
patients in group 2 (n = 9) did not have TE inserted and received postoperative
RT. Finally, those in group 3 (n = 27) did not receive postoperative RT.
Multivariate analysis was performed to identify the risk factors associated with
recurrence-free survival within 3 years. Younger age, history of LPS treatment,
and RT after TE insertion (group 1 vs group 2 or 3) were significantly favorable
factors influencing 3-year recurrence-free survival.TE insertion after LPS
resection is associated with increased 3-year recurrence-free survival, most
likely because it allows effective delivery of postoperative RT.
PMID- 27512858
TI - Awake nasotracheal fiberoptic intubation and self-positioning followed by
anesthesia induction in prone patients: A pilot observational study.
AB - Anesthesia followed by placement in the prone position takes time and may result
in complications. This study aimed to evaluate the feasibility of awake
nasotracheal fiberoptic intubation and self-positioning followed by anesthesia
induction in prone-positioned patients under general anesthesia.Sixty-two
patients (ASA physical status I-II) scheduled for awake nasotracheal fiberoptic
intubation and prone self-positioning before surgery under general anesthesia
were selected. Patient preparation began with detailed preoperative counseling
regarding the procedure. Premedication with sedative and antisialagogue was
followed by airway anesthesia with topical lidocaine; then, awake nasotracheal
fiberoptic intubation was carried out. The patients then positioned themselves
comfortably before induction of general anesthesia. The changes in systolic blood
pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), incidence of
coughing or gagging, and rate pressure product (RPP) were assessed. Statistical
analysis was performed with repeated-measures one-way analysis of variance.Fifty
eight of the 62 patients completed prone self-positioning smoothly. Compared with
values before intubation, SBP, DBP, HR, and RPP were slightly increased after
intubation, although the difference was not statistically significant (P > 0.05).
One patient had moderate coughing and 1 patient had gagging during prone self
positioning, which were tolerable.These findings indicated that awake
nasotracheal fiberoptic intubation and self-positioning followed by induction of
anesthesia is safe and feasible alternative to routine prone positioning after
induction of general anesthesia.
PMID- 27512859
TI - Laparoscopic duodenum-preserving pancreatic head resection: A case report.
AB - BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas are uncommon
neoplasms and are potentially malignant. Complete resection is advised due to
rare recurrence and metastasis. Duodenum-preserving pancreatic head resection
(DPPHR) is indicated for SPNs located in the pancreatic head and is only
performed using the open approach. To the best of our knowledge, there are no
reports describing laparoscopic DPPHR (LDPPHR) for SPNs. METHODS: Herein, we
report a case of 41-year-old female presented with a 1-week history of epigastric
abdominal discomfort, and founded an SPN of the pancreatic head by abdominal
computed tomography/magnetic resonance, who was treated by radical LDPPHR without
complications, such as pancreatic fistula and bile leakage. Histological
examination of the resected specimen confirmed the diagnosis of SPN. RESULTS: The
patient was discharged 1 week after surgery following an uneventful postoperative
period. She was followed up 3 months without readmission and local recurrence
according to abdominal ultrasound. CONCLUSION: LDPPHR is a safe, feasible, and
effective surgical procedure for SPNs.
PMID- 27512860
TI - Incidence and risk factors for the progression of proximal junctional kyphosis in
degenerative lumbar scoliosis following long instrumented posterior spinal
fusion.
AB - The aim of this study was to identify the prevalence of proximal junctional
kyphosis (PJK) in degenerative lumbar scoliosis (DLS) following long instrumented
posterior spinal fusion, and to search for predictable risk factors for the
progression of junctional kyphosis.In total 98 DLS patients with a minimum 2-year
follow-up were reviewed prospectively. According to the occurrence of PJK at the
last follow-up, patients were divided into 2 groups: PJK group and non-PJK group.
To investigate risk values for the progression of PJK, 3 categorized factors were
analyzed statistically: patient characteristics-preoperative data of age, sex,
body mass index (BMI), bone mineral density (BMD) were investigated; surgical
variables-the most proximal and distal levels of the instrumentation, the number
of instrumented levels; pre- and postoperative radiographic parameters include
the scoliotic angle, sagittal vertical axis, thoracic kyphosis, thoracolumbar
junctional angle, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral
slope.PJK was developed in 17 of 98 patients (17.3%) until to the final follow-up
and were enrolled as the PJK group, and 81 patients without PJK at final follow
up were enrolled as the non-PJK group. There was no statistically significant
difference between the 2 groups in age at operation (P = 0.900). The patient's
sex was excluded in statistical analysis because of the predominance of female
patients. There were statistically significant difference between the 2 groups in
BMI ([25.5 +/- 1.7] kg/m in the PJK group and [23.6 +/- 1.9] kg/m in the non-PJK
group, P < 0.001) and BMD ([-1.4 +/- 0.8] g/cm in the PJK group and [-0.7 +/-
0.3] g/cm in the non-PJK group, P < 0.001). No specific surgery-related variables
were found to be associated with an increased risk of developing PJK, except when
the most proximal instrumented vertebrae stopped at thoracolumbar junction (T11
L1). The upper instrumentation vertebrae (UIV) at thoracolumbar junction was more
common in the PJK group than that in the non-PJK group (P = 0.007). No
preoperative and early postoperative variable did reveal a statistically
significant difference between the 2 groups. When included in a multivariate
logistic regression model, BMI>25 kg/m, osteoporosis, and UIV at thoracolumbar
junction were independently associated with PJK.In conclusion, osteoporosis,
obesity, and UIV at thoracolumbar junction are risk factors for the development
and progression of PJK in DLS patients following long instrumented posterior
spinal fusion. Antiosteoporosis treatment extends the fusion level above the
thoracolumbar region and controlling body weight before and after surgery could
provide opportunities to reduce the rate of PJK and to improve therapeutic
outcomes.
PMID- 27512861
TI - Effectiveness of FDG-PET/CT for evaluating early response to induction
chemotherapy in head and neck squamous cell carcinoma: A systematic review.
AB - BACKGROUND: F-Fluoro-Deoxy-Glucose Positron Emission Tomography with Computed
Tomography (F-FDG PET/CT) may be a powerful tool to predict treatment outcome. We
aimed to review the effectiveness of F-FDG PET/CT in the assessment of early
response to induction chemotherapy (IC) in patients with advanced Head and Neck
Squamous Cell Cancer (HNSCC) without previous treatment. METHODS: PubMed,
Cochrane Library, Science Direct and Web of Science were searched to May 2016.
Reference lists of the included articles and additional studies identified by one
nuclear medicine expert were screened for potential relevant studies that
investigated the effectiveness of F-FDG PET/CT performed before and after IC.
Three authors independently screened all retrieved articles, selected studies
that met inclusion criteria and extracted data. The methodology of the selected
studies was evaluated by using the risk of bias checklist of the Agency for
Healthcare Research and Quality (AHRQ). RESULTS: Seven out of 170 eligible
studies met our inclusion criteria. A total of 207 advanced HNSCC patients were
evaluated with F-FDG PET/CT at baseline and after IC in the selected articles.
Six from seven studies concluded that F-FDG PET/CT allowed early evaluation
response to IC and predicted survival outcomes. CONCLUSION: The present
systematic review confirms the potential value of F-FDG PET/CT as a diagnostic
tool for early IV response assessment in HNSCC patients. However, the lack of
standard definitions for response criteria and heterogeneous IC protocols
indicate the need to further studies in order to better define the role of F-FDG
PET/CT in these patients.
PMID- 27512862
TI - Metabolic syndrome is a risk factor for adenoma occurrence at surveillance
colonoscopy: A single-center experience in Korea.
AB - We investigated the risk factors for adenoma occurrence at surveillance
colonoscopy, especially focusing on patient characteristics, including metabolic
factors.Surveillance colonoscopy intervals depend on baseline adenoma
characteristics. However, patients' characteristics may also influence the
occurrence of adenomas.Of 62,171 asymptomatic subjects who underwent colonoscopy
for a health check-up between 2010 and 2011, 4869 subjects who underwent follow
up colonoscopy between 2012 and 2013 were included in this longitudinal study.
The risk of adenoma occurrence was assessed using Cox proportional hazards
modeling.Of 4869 subjects, 2827 (58.1%), 1619 (33.3%), and 423 (8.7%) were
assigned to the normal, low-risk, and high-risk groups, respectively, according
to baseline adenoma characteristics. The mean interval between initial and follow
up colonoscopy was 2.2 +/- 0.6 years. Certain patient factors, including older
age (>=50 years; adjusted hazard ratio [aHR], 2.08; 95% CI, 1.73-2.49), male sex
(aHR, 1.69; 95% CI, 1.30-2.19), metabolic syndrome (MetS) (aHR, 1.28; 95% CI,
1.09-1.51), obesity (aHR, 1.17; 95% CI, 1.02-1.34), elevated fasting blood
glucose levels (aHR, 1.37; 95% CI, 1.19-1.58), and elevated triglyceride levels
(aHR, 1.19; 95% CI, 1.03-1.37), as well as baseline adenoma characteristics, were
associated with a higher risk of adenoma occurrence at follow-up colonoscopy. The
cumulative incidence of adenoma occurrence in the high-risk group was higher than
that in the low-risk group, whereas the incidence in the high-risk group without
MetS was comparable with that in the low-risk group with MetS.Patient
characteristics, such as MetS, obesity, older age, and male sex, in addition to
adenoma characteristics, were independent risk factors for adenoma occurrence at
surveillance colonoscopy. These patient characteristics may be considered in
surveillance colonoscopy intervals.
PMID- 27512863
TI - Perimenopausal syndrome and mood disorders in perimenopause: prevalence,
severity, relationships, and risk factors.
AB - Limited information was focused on perimenopausal syndrome and mood disorders
(depression and anxiety) in a specific population: perimenopausal women. We aimed
to investigate the prevalence and severity of perimenopausal syndrome and mood
disorders, and to analyze their relationships and risk factors in perimenopausal
women in Shanghai, China.A cross-sectional study was performed on 1062 women aged
40 to 60 years from 3 communities. The general conditions questionnaire,
Kupperman index, self-rating depression scale, and self-rating anxiety scale were
used. A multivariable logistic regression analysis was performed to identify risk
factors for perimenopausal syndrome and mood disorders.The prevalence of
perimenopausal syndrome, depression and anxiety, which were primarily associated
with mild symptoms, was 10.92%, 25.99%, and 12.62%, respectively. The differences
in the prevalence and severity of perimenopausal syndrome, in the prevalence of
depression, and in the severity of anxiety in different age groups were
statistically significant (P < 0.001, P = 0.028, P = 0.003, P = 0.002,
respectively). The relationships between perimenopausal syndrome and mood
disorders were strong and positive (P < 0.001). It was found that age, employment
status, personality characteristics, menstruation, and constipation were risk
factors for perimenopausal syndrome, but monthly household income was a
protective factor. Also, higher income and better medical insurance were
beneficial to depression. However, disharmonious family relationships, irregular
menstruation, constipation, and severity of perimenopausal syndrome were harmful
to depression. For anxiety, attitudes to children status, cesarean section times,
and constipation were risk factors.We concluded that perimenopausal syndrome and
mood disorders are common in perimenopausal women in Shanghai, whose associations
are strong and positive. Many risk factors are associated with and shared between
perimenopausal syndrome and mood disorders. Therefore, appropriate management of
perimenopause is needed to alleviate the conditions.
PMID- 27512864
TI - Zero-fluoroscopy catheter ablation of severe drug-resistant arrhythmia guided by
Ensite NavX system during pregnancy: Two case reports and literature review.
AB - BACKGROUND: Cardiac arrhythmias can occur during pregnancy. Owing to radiation
exposure and other uncertain risks for the mother and fetus, catheter ablation
has rarely been performed and is often delayed until the postpartum period. We
reported 2 pregnant women who were experiencing severe arrhythmias and were
successfully ablated without fluoroscopic guidance. We also carried out a
literature review of cases of pregnant women who underwent zero-fluoroscopy
ablation. METHODS AND RESULTS: One woman had drug-resistant and poorly tolerated
frequent premature ventricular contraction (PVC) and ventricular tachycardia
(VT). The other one had persistent and hardly terminated supraventricular
tachycardia (SVT) via a right accessory pathway. The 2 patients were successfully
underwent zero-fluoroscopy ablation guided by Ensite NavX system. The procedure
time was 42 and 71 minutes, respectively. CONCLUSION: Catheter ablation of SVT or
PVC/VT in pregnant patients can be safely and effectively performed with a
completely zero-fluoroscopy approach guided by the Ensite NavX system. In the
case of a drug refractory, life-threatening arrhythmia during pregnancy, catheter
ablation may be considered.
PMID- 27512865
TI - Plasma angiopoietin-2 is persistently elevated after non-small cell lung cancer
surgery and stimulates angiogenesis in vitro.
AB - Angiopoietin-2 (Ang2) is a key proangiogenic factor, but its role in surgery
induced angiogenesis, a possible cause of cancer recurrence, is still elusive.We
measured the plasma Ang2 levels in healthy controls (n = 42) and stage I-IV
perioperative nonsmall cell lung cancer (NSCLC) patients (n = 227) with enzyme
linked immunosorbent assay, and examined the impact of Ang2 in the plasmas on in
vitro angiogenesis and proliferation of human umbilical vein endothelial cells
and human microvascular endothelial cells.Ang2 plasma levels are significantly
increased in untreated NSCLC patients (2697 +/- 1354 pg/mL) compared to control
(1473 +/- 560.6 pg/mL) and positively associated with disease stage but not with
histology. Ang2 plasma levels in stage I-IIIA NSCLC patients (n = 154) are
elevated after the standard open thoracic surgery, following an approximate
pattern to increase quickly in the 1st postoperative days (PODs, from
preoperative 2342 +/- 1084 to POD1: 4485 +/- 1617 and POD3: 5370 +/- 1879 pg/mL),
reach the peak about 2 weeks later (POD14: 6099 +/- 2280 pg/mL), drop slowly
thereafter (POD28: 3877 +/- 1388 and POD42: 3365 +/- 1189 pg/mL), and remain
significantly higher than preoperative 8 weeks after the procedure (POD56: 2937
+/- 943.3 pg/mL). The postoperative plasmas enhance in vitro angiogenesis and
Ang2 removal from the plasmas can counteract the effect. The postoperative
plasmas stimulate endothelial proliferation independently of Ang2.These results
suggest that plasma Ang2 increases after NSCLC surgery and contributes to the
proangiogenic property of the postoperative plasmas, thus supporting the possible
administration of anti-Ang2 therapy for NSCLC in postoperative adjuvant setting.
PMID- 27512867
TI - Decreased retinal nerve fiber layer thickness in patients with obstructive sleep
apnea syndrome: A meta-analysis.
AB - OBJECTIVE: To investigate the changes of retinal nerve fiber layer (RNFL)
thickness in obstructive sleep apnea syndrome (OSAS) patients. METHODS: Relevant
studies were selected from 3 major literature databases (PubMed, Cochrane
Library, and EMBASE) without language restriction. Main inclusion criteria is
that a case-control study in which RNFL thickness was measured by a commercial
available optical coherence tomography (OCT) in OSAS patients. Meta-analysis was
performed using STATA 12.0 software. Efficacy estimates were evaluated by
weighted mean difference with corresponding 95% confidence intervals (CIs).
Primary outcome evaluations were: the average changes of RNFL thickness in total
OSAS patients, subgroup analysis of RNFL thickness changes in patients of
different OSAS stages, and subgroup analysis of 4-quadrant RNFL thickness changes
in total OSAS patients. RESULTS: Of the initial 327 literatures, 8 case-control
studies with 763 eyes of OSA patients and 474 eyes of healthy controls were
included (NOS scores >=6). For the people of total OSAS, there had an average
2.92 MUm decreased RNFL thickness compared with controls (95% CI: -4.61 to -1.24,
P = 0.001). For subgroup analysis of OSAS in different stages, the average
changes of RNFL thickness in mild, moderate, severe, and moderate to severe OSAS
were 2.05 (95% CI: -4.40 to 0.30, P = 0.088), 2.32 (95% CI: -5.04 to 0.40, P =
0.094), 4.21 (95% CI: -8.36 to -0.06, P = 0.047), and 4.02 (95% CI: -7.65 to
0.40, P = 0.03), respectively. For subgroup analysis of 4-quadrant, the average
changes of RNFL thickness in Superior, Nasal, Inferior, and Temporal quadrant
were 2.43 (95% CI: -4.28 to -0.57, P = 0.01), 1.41 (95% CI: -3.33 to 0.51, P =
0.151), 3.75 (95% CI: -6.92 to -0.59, P = 0.02), and 0.98 (95% CI: -2.49 to 0.53,
P = 0.203), respectively. CONCLUSION: Our study suggests that RNFL thickness in
OSAS patients is much thinner than healthy population, especially in superior and
inferior quadrant. The impact of OSAS disease on RNFL and visual function should
be taken seriously in the further study.
PMID- 27512866
TI - Venous thromboembolism has the same risk factors as atherosclerosis: A PRISMA
compliant systemic review and meta-analysis.
AB - BACKGROUND: Previous studies have shown that idiopathic pulmonary embolism is
positively associated with other cardiovascular events, such as myocardial
infarction and stroke, suggesting a potentially important association between
atherosclerosis risk factors and venous thromboembolism (VTE). We performed a
meta-analysis to evaluate the correlation between risk factors for
atherosclerosis and VTE. METHODS: In December 2014, we searched MEDLINE and
EMBASE for studies evaluating the associations between VTE and risk factors for
atherosclerosis and pooled outcome data using random-effects meta-analysis. In
addition, we analyzed publication bias. RESULTS: Thirty-three case-control and
cohort studies with a total of 185,124 patients met the inclusion criteria. We
found that participants with body mass index (BMI) >=30 kg/m had a significantly
higher prevalence of VTE than those with BMI <30 kg/m in both case-control
studies (odds ratio [OR] = 2.45, 95% confidence interval [CI]: 1.78-3.35) and
cohort studies (relative risk [RR] = 2.39, 95% CI: 1.79-3.17). VTE was more
prevalent in patients with hypertension than without hypertension (OR = 1.40, 95%
CI: 1.06-1.84; RR = 1.36, 95% CI: 1.11-1.67). The findings were similar for VTE
prevalence between patients with and without diabetes (OR = 1.78, 95% CI: 1.17
2.69; RR = 1.41, 95% CI: 1.20-1.66). Current smoking was significantly associated
with VTE prevalence in case-control studies (OR = 1.34, 95% CI: 1.01-1.77), but
not in cohort studies (RR = 1.29, 95% CI: 0.96-1.72). In addition, we found that
total cholesterol and triglyceride concentrations were significantly higher in
patients with VTE than without VTE (weighted mean differences [WMD] = 8.94 mg/dL,
95% CI: 3.52-14.35 mg/dL, and WMD = 14.00 mg/dL, 95% CI: 8.85-19.16 mg/dL,
respectively). High-density lipoprotein cholesterol concentrations were
significantly lower in patients with VTE than without VTE (WMD = -2.03 mg/dL, 95%
CI: -3.42 to -0.63 mg/dL). Higher quality studies were more homogeneous, but
confirmed the same significant associations. CONCLUSIONS: Based on our systematic
review and meta-analysis, we observed a significant association between VTE and
the risk factors for atherosclerosis. These results may make an important
contribution to clinical practice regarding VTE treatment.
PMID- 27512868
TI - Impact of protease inhibitors on the evolution of urinary markers: Subanalyses
from an observational cross-sectional study.
AB - Kidney injury (defined as the presence of albuminuria, proteinuria, glycosuria
[without hyperglycemia], hematuria, and/or renal hypophosphatemia) is an emerging
problem in human immunodeficiency virus (HIV)-infected patients, although few
data are available on the role of protease inhibitors (PIs) in this condition.To
determine the time to kidney injury in a cohort of HIV-infected patients
receiving a PI-containing regimen.We report the results of a subanalysis of a
published cross-sectional study. The subanalysis included only patients receiving
PI-containing regimens for more than 6 months (377 of the overall 970 patients).
We determined associated factors and constructed receiver operating
characteristic curves to estimate time to kidney injury depending on the PI
used.The percentage of patients with kidney injury was 27.7% for darunavir, 27.9%
for lopinavir, and 30% for atazanavir. Time to kidney injury was as follows: 229
days for atazanavir/ritonavir (area under the curve [AUC], 0.639; sensitivity,
0.89; specificity, 0.41); 332 days for atazanavir/ritonavir plus tenofovir (AUC,
0.603; sensitivity, 0.75; and specificity, 0.29); 318 days for nonboosted
atazanavir (AUC, 0.581; sensitivity, 0.89; and specificity, 0.29); 478 days for
lopinavir/ritonavir (AUC, 0.566; sensitivity, 0.864; and specificity, 0.44); 1339
days for lopinavir/ritonavir plus tenofovir (AUC, 0.667; sensitivity, 0.86; and
specificity, 0.77); 283 days for darunavir/ritonavir (AUC, 0.523; sensitivity,
0.80; and specificity, 0.261); and 286 days for darunavir/ritonavir plus
tenofovir (AUC, 0.446; sensitivity, 0.789; and specificity, 0.245). The use of
lopinavir/ritonavir without tenofovir was a protective factor (odds ratio =
1.772; 95%CI, 1.070-2.93; P = 0.026).For all PIs, the percentage of patients with
kidney injury exceeded 27%, irrespective of tenofovir use. The longest time to
kidney injury was recorded with lopinavir/ritonavir. These results demonstrate
the need for renal monitoring, including urine samples, in patients receiving a
PI-based regimen, even when tenofovir is not used concomitantly.
PMID- 27512869
TI - Knowledge, attitudes, and beliefs about HIV pre-exposure prophylaxis among US Air
Force Health Care Providers.
AB - Providers are central to effective implementation of HIV pre-exposure prophylaxis
(PrEP). Primary care providers (PCP) and infectious disease physicians (ID) in
the US Air Force (USAF) participated in a cross-sectional survey regarding
knowledge, attitudes, and beliefs toward HIV PrEP. Characteristics associated
with PrEP knowledge were assessed in univariate and multivariate analyses.Among
403 (40% of 1015 providers) participants, 9% (PCP 383, ID 20) ever prescribed
PrEP. In univariate analysis, years in practice, number of HIV-infected patients
treated in the past 12 months, past prescription of antiretrovirals for HIV
prevention, frequency of prescribing PrEP in the past 12 months, and ever being
questioned by a patient about PrEP were associated with PrEP knowledge (P <
0.05). In multivariate analysis, providers who had ever prescribed
antiretrovirals to prevent HIV (AOR: 2.37, 95% CI: 1.27-4.42) had greater odds of
high PrEP knowledge. Despite concerns about medication side effects (overall 67%:
PCP 68%, ID 85%) and prescribing PrEP without clear evidence (overall 60%: PCP
65%, ID 62%), 64% (PCP 65%, ID 85%) of participants indicated PrEP should be
offered in the Military Health System and 68% (PCP 70%, ID 100%) disagreed with
the statement that their patient population was not at risk for HIV
infection.Successful PrEP implementation in the USAF will require continued
education and training of primary care providers to improve knowledge and
mitigate concerns about PrEP.
PMID- 27512870
TI - Risk assessment model for invasive breast cancer in Hong Kong women.
AB - No risk assessment tool is available for identifying high risk population of
breast cancer (BCa) in Hong Kong. A case-control study including 918 BCa cases
and 923 controls was used to develop the risk assessment model among Hong Kong
Chinese women.Each participant received an in-depth interview to obtain their
lifestyle and environmental risk factors. Least absolute shrinkage and selection
operator (LASSO) selection model was used to select the optimal risk factors
(LASSO-model). A risk score system was constructed to evaluate the cumulative
effects of selected factors. Bootstrap simulation was used to test the internal
validation of the model. Model performance was evaluated by receiver-operator
characteristic curves and the area under the curve (AUC).Age, number of parity,
number of BCa cases in 1st-degree relatives, exposure to light at night, and
sleep quality were the common risk factors for all women. Alcohol drinking was
included for premenopausal women; body mass index, age at menarche, age at 1st
give birth, breast feeding, using of oral contraceptive, hormone replacement
treatment, and history of benign breast diseases were included for postmenopausal
women. The AUCs were 0.640 (95% CI, 0.598-0.681) and 0.655 (95% CI, 0.621-0.653)
for pre- and postmenopausal women, respectively. Further subgroup evaluation
revealed that the model performance was better for women aged 50 to 70 years or
ER-positive.This BCa risk assessment tool in Hong Kong Chinese women based on
LASSO selection is promising, which shows a slightly higher discriminative
accuracy than those developed in other populations.
PMID- 27512871
TI - Prevalence of cardiac sarcoidosis in white population: a case-control study:
Proposal for a novel risk index based on commonly available tests.
AB - Cardiac sarcoidosis (CS) is a life-threatening and underdiagnosed manifestation
of the disease, which requires a complicated and expensive diagnostic pathway.
There is a need for simple tool for practitioners to determine the risk of CS
without access to specialized equipment.The aim of study was to determine the
prevalence of CS in a group of patients diagnosed with or followed up because of
sarcoidosis. A secondary objective was the search for factors associated with
heart involvement.We performed a prospective case-control study (screening
analysis) in consecutive sarcoidosis patients collected from October 2012 to
September 2015. Cardiac magnetic resonance (CMR) imaging was performed to confirm
or exclude cardiac involvement in all patients. The study was conducted in a
hospital-based referral center for patients with sarcoidosis and other
interstitial lung diseases.Analysis was performed in a group of 201 patients (all
white) with biopsy-proven sarcoidosis, mean age 41.4 +/- 10.2, 121 of them
(60.2%) males. Four patients with previously recognized cardiac diseases, which
make CMR imaging for CS inconclusive, were not included.Cardiac involvement was
detected by CMR in 49 patients (24.4%). Factors associated with an increased risk
of CS (univariate analyses) included male sex (odds ratio [OR]: 2.5; 1.21-5.16, P
= 0.01), cardiac-related symptoms (OR: 3.53; 1.81-6.89, P = 0.0002),
extrathoracic sarcoidosis (OR: 3.48; 1.77-6.84, P = 0.0003), elevated serum NT
proBNP (OR: 3.82; 1.55-9.42, P = 0.004), any electrocardiography abnormality (OR:
5.38; 2.48-11.67, P = 0.0001), and contemporary radiological progression
sarcoidosis in the lungs (OR: 2.98; 1.52-5.84, P = 0.001). Abnormalities in
echocardiography and Holter ECG were also risk factors, but not significant in
multivariate analyses. A CS Risk Index was developed using a multivariate model
to predict CS, achieving an accuracy of 82%, sensitivity of 50%, specificity of
94%, and likelihood ratio 8.1.CS was detected in one fourth of patients. A CS
Risk Index based on the results of easily accessible tests is cost-effective and
may help to identify patients who should be urgently referred for further
diagnostic procedures.
PMID- 27512872
TI - Successful kidney transplantation after desensitization in a patient with
positive flow crossmatching and donor-specific anti-HLA-DP antibody: A Case
report.
AB - BACKGROUND: Traditionally, the presence of antibodies against human leukocyte
antigen (HLA)-C and DP was considered to be associated with only a low risk of
antibody-mediated rejection (ABMR) in kidney transplantation (KT), because the
antigenicities of these proteins are weak. However, the clinical effects of HLA-C
and -DP donor-specific HLA antibodies (DSHAs) have recently been reevaluated.
METHODS: Here, we report the case of a retransplant patient with positive flow
cytometry crossmatch (FCXM) and high level of HLA-DP DSHA who was desensitized
using rituximab, plasmapheresis, and intravenous immunoglobulin. RESULTS: The
epitope-based antibody reactivity was identified that the positive B-cell FCXM in
our patient was attributable to the specific epitope. The patient underwent a
successful retransplantation and has continued to do well for 10 month after KT.
CONCLUSION: If an HLA-DP DSHA is present, it is important to detect any
mismatched HLA-DP epitope pretransplantation and to monitor HLA-DP levels
carefully. According to previous reports, anti-HLA-DP DSHA can induce ABMR soon
after transplantation, but such ABMR can be prevented by pretransplantation
desensitization and careful monitoring of DSHA levels.
PMID- 27512873
TI - Prediction of motor outcome by shoulder subluxation at early stage of stroke.
AB - We attempted to determine whether shoulder subluxation at the early stage of
stroke can predict motor outcome in relation to the corticospinal tract (CST)
state on diffusion tensor tractography.Fifty-nine stroke patients with severe
hemiparesis were recruited. The patients were classified according to the
distance of shoulder subluxation (group A: >=2 cm, group B: <2 cm) and the
affected CST on diffusion tensor tractography at the first evaluation (CST type A
the CST was discontinued at the stroke lesion; CST type B-the integrity of the
CST was preserved). Motor function of the patients was evaluated twice (first:
beginning of rehabilitation-24.1 +/- 16.6 days; second: discharge after first
rehabilitation-58.5 +/- 24.1 days) using the Medical Research Council score,
Motricity Index, and Modified Brunnstrom Classification.Regarding the improvement
of the Medical Research Council for the finger extensor and upper Motricity
Index, the order in terms of better recovery was as follows: group B-type B,
group A-type B, group B-type A, and group A-type A (P < 0.05). The distance of
shoulder subluxation showed significant correlation with improvement of the
finger extensor (moderate negative correlation, r = -0.37) and improvement of the
Modified Brunnstrom Classification (weak negative correlation, r = -0.29) (P <
0.05).The presence of shoulder subluxation at the early stage of stroke can be a
predictor of motor outcome of the affected upper extremity and the degree of
shoulder subluxation can be a predictor of the motor function of the affected
hand. Therefore, our results suggest that shoulder subluxation in relation to the
affected CST state at the early stage of stroke can be a prognostic factor for
motor outcome.
PMID- 27512875
TI - Effects of postimplantation systemic inflammatory response on long-term clinical
outcomes after endovascular aneurysm repair of an abdominal aortic aneurysm.
AB - The aim of this study was to determine the association between postimplantation
syndrome (PIS) and long-term clinical outcomes after elective endovascular
aneurysm repair (EVAR) of an abdominal aortic aneurysm.In this single-center,
observational cohort study, a total of 204 consecutive patients undergoing EVAR
were included. Primary outcome was long-term mortality from any cause; secondary
outcomes included long-term mortality, systemic or implant-related complications,
and secondary therapeutic procedures.The diagnosis of PIS was established in 64
patients (31.4%). PIS patients were more likely to receive woven polyester
endografts and have a longer postoperative hospital stay and lower incidence of
type II endoleaks. In multivariate analysis, PIS was significantly associated
with a decreased risk of developing type II endoleaks (P = 0.044). During follow
up period of 44 months, clinical outcomes showed no significant differences in
mortality (P = 0.876), systemic (P = 0.668), or implant-related complications (P
= 0.847), although rates of secondary therapeutic procedure were significantly
higher in non-PIS patients (P = 0.037). The groups had similar rates of overall
survival (P = 0.761) and other clinical outcomes (P = 0.562).Patients with and
without PIS had similar long-term overall survival rates and other clinical
outcomes. PIS was beneficial in preventing type II endoleaks during postoperative
period.
PMID- 27512874
TI - Comparative efficacy of interventions on nonalcoholic fatty liver disease
(NAFLD): A PRISMA-compliant systematic review and network meta-analysis.
AB - BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has
significantly increased over the last decades. Despite existence of several
interventions, there remains unclear which interventions work the best. METHODS:
A systematic review and network meta-analysis of randomized trials comparing
efficacy of all treatment options in NAFLD were performed to determine
comparative efficacy and safety of interventions in the management of NAFLD.
Several electronic databases were searched up to Nov 15, 2015. Outcomes include
liver histological outcomes (i.e., fibrosis), all-cause mortality, cirrhosis, and
safety. A network meta-analysis was applied to estimate pooled risk ratios (RR).
Quality of evidence was assessed using GRADE criteria. RESULTS: A total of 44
studies (n = 3802) were eligible. When compared with placebo, obeticholic acid
(OCA) was the only intervention that significantly improved fibrosis with RR (95%
CI) of 1.91 (1.15, 3.16), while pentoxyfylline (PTX) demonstrated improved
fibrosis without statistical significance with RR (95% CI) of 2.27 (0.81, 6.36).
Only thiazolidinedione (TZD) and vitamin E use resulted in significant increase
in resolution of NASH, while OCA, TZD, and vitamin E significantly improved other
outcomes including NAS, steatosis, ballooning, and inflammation outcomes. Quality
of evidence varied from very low (i.e., metformin, PTX on mean change of
ballooning grade) to high (OCA, TZD, vitamin E on improving histological
outcomes). Limitations of this study were lack of relevant long-term outcomes
(e.g., cirrhosis, death, safety), possible small study effect, and few head-to
head studies. CONCLUSIONS: Our study suggests potential efficacy of OCA, TZD, and
vitamin E in improving histologic endpoints in NAFLD. These findings are however
based on a small number of studies. Additional studies are awaited to strengthen
this network meta-analysis.
PMID- 27512876
TI - A new automatic blood pressure kit auscultates for accurate reading with a
smartphone: A diagnostic accuracy study.
AB - The widely used oscillometric automated blood pressure (BP) monitor was
continuously questioned on its accuracy. A novel BP kit named Accutension which
adopted Korotkoff auscultation method was then devised. Accutension worked with a
miniature microphone, a pressure sensor, and a smartphone. The BP values were
automatically displayed on the smartphone screen through the installed App. Data
recorded in the phone could be played back and reconfirmed after measurement.
They could also be uploaded and saved to the iCloud. The accuracy and consistency
of this novel electronic auscultatory sphygmomanometer was preliminarily verified
here. Thirty-two subjects were included and 82 qualified readings were obtained.
The mean differences +/- SD for systolic and diastolic BP readings between
Accutension and mercury sphygmomanometer were 0.87 +/- 2.86 and -0.94 +/- 2.93 mm
Hg. Agreements between Accutension and mercury sphygmomanometer were highly
significant for systolic (ICC = 0.993, 95% confidence interval (CI): 0.989-0.995)
and diastolic (ICC = 0.987, 95% CI: 0.979-0.991). In conclusion, Accutension
worked accurately based on our pilot study data. The difference was acceptable.
ICC and Bland-Altman plot charts showed good agreements with manual measurements.
Systolic readings of Accutension were slightly higher than those of manual
measurement, while diastolic readings were slightly lower. One possible reason
was that Accutension captured the first and the last korotkoff sound more
sensitively than human ear during manual measurement and avoided sound missing,
so that it might be more accurate than traditional mercury sphygmomanometer. By
documenting and analyzing of variant tendency of BP values, Accutension helps
management of hypertension and therefore contributes to the mobile heath service.
PMID- 27512877
TI - Efficacy of different dipeptidyl peptidase-4 (DPP-4) inhibitors on metabolic
parameters in patients with type 2 diabetes undergoing dialysis.
AB - Hyperglycemia is associated with increased mortality and morbidity in patients
with type 2 diabetes mellitus (T2DM) who are undergoing dialysis. Although
dipeptidyl peptidase-4 (DPP-4) inhibitors have been widely used in end-stage
renal disease (ESRD) patients with T2DM, there are few studies on their efficacy
in this population. We studied the effect of 3 different DPP-4 inhibitors on
metabolic parameters in ESRD patients with T2DM.Two hundred ESRD patients with
T2DM who were treated with DPP-4 inhibitors (sitagliptin, vildagliptin, or
linagliptin) were enrolled and analyzed retrospectively. The changes in glycated
hemoglobin (HbA1c), fasting plasma glucose, and lipid profiles were assessed
before and after 3 months of treatment with DPP-4 inhibitors. Subgroup analysis
was done for each hemodialysis (HD) and peritoneal dialysis (PD) group.There was
no significant difference in the decrease in the HbA1c level among sitagliptin,
vildagliptin, and linagliptin treatment groups (-0.74 +/- 1.57, -0.39 +/- 1.45,
and -0.08 +/- 1.40, respectively, P = 0.076). The changes in fasting blood
glucose and lipid profiles were also not significantly different. In HD patients
(n = 115), there was no difference in the HbA1c level among the 3 groups. In
contrast, in PD patients (n = 85), HbA1c was reduced more after 3 months of
treatment with sitagliptin compared with vildagliptin and linagliptin (-1.58 +/-
0.95, -0.46 +/- 0.98, -0.04 +/- 1.22, respectively, P = 0.001).There was no
significant difference in the glucose-lowering effect between the different DPP-4
inhibitors tested in ESRD patients. In PD patients, sitagliptin tends to lower
the HbA1c level more than the other inhibitors. The glucose-lowering efficacy of
the 3 DPP-4 inhibitors was comparable.
PMID- 27512878
TI - Clinical characteristics and genetic profiles of 174 patients with X-linked
agammaglobulinemia: Report from Shanghai, China (2000-2015).
AB - X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency. XLA
patients typically present with very low numbers of peripheral B cells and a
profound deficiency of all immunoglobulin isotypes. Most XLA patients carry
mutations in Bruton tyrosine kinase (BTK) gene.The genetic background and
clinical features of 174 Chinese patients with XLA were investigated. The
relationship between specific BTK gene mutations and severity of clinical
manifestations was also examined. Mutations were graded from mild to severe based
on structural and functional prediction through bioinformatics analysis.One
hundred twenty-seven mutations were identified in 142 patients from 124 families,
including 45 novel mutations and 82 recurrent mutations that were distributed
over the entire BTK gene sequence. Variation in phenotypes was observed, and
there was a tendency of association between genotype and age of disease
onset.This report constitutes the largest group of patients with BTK mutations in
China. A genotype-phenotype correlation was observed in this study. Early
diagnosis of congenital agammaglobulinemia should be based on clinical symptoms,
family history, and molecular analysis of the BTK gene.
PMID- 27512879
TI - Layer-specific analysis of dobutamine stress echocardiography for the evaluation
of coronary artery disease.
AB - Although dobutamine stress echocardiography (DSE) is a well-defined tool for the
diagnosis of coronary artery disease (CAD), false-negative and false-positive
results still occur. This study investigated the diagnostic role of layer
specific analysis using 2-dimensional speckle-tracking echocardiography (STE)
during DSE.A total of 121 patients who underwent DSE and showed normal wall
motion and ejection fraction during baseline echocardiography were enrolled. All
patients underwent coronary angiography after DSE within 2 weeks. The patients
were divided into the following 4 groups according to DSE results and CAD status:
negative DSE with no significant CAD (n = 73), positive DSE with significant CAD
(n = 16), negative DSE with significant CAD (n = 17), and positive DSE with no
significant CAD (n = 15). Layer-specific global longitudinal strain (GLS) was
assessed in the endocardium, mid-myocardium, and epicardium by STE
techniques.Patients with significant CAD were older, more male and showed higher
glucose level compared to patients without CAD. But coronary risk factors and
previous medications were not different between patients with and without CAD.
There were no significant differences in whole myocardium or layer-specific GLS
found in the baseline echocardiography. During recovery echocardiography,
endocardial GLS was significantly different between patients with and without
CAD, regardless of the DSE results. A receiver-operating characteristic curve
analysis showed that endocardial GLS (>-16%) was superior for identifying
significant CAD during the DSE recovery stage. Diagnostic accuracy was improved
by applying the results of endocardial GLS compared with visual estimation of
DSE.The assessment of layer-specific strain by STE during DSE was feasible, and
the evaluation of poststress endocardial function is a more sensitive tool for
the detection of CAD.
PMID- 27512880
TI - Modeling the effectiveness of nebulized terbutaline for decompensated chronic
obstructive pulmonary disease patients in the emergency department.
AB - Short-acting beta2-agonists (SABA) are widely used in the emergency department
(ED) to treat patients with decompensated chronic obstructive pulmonary disease
(COPD). We sought to model the effectiveness of nebulized SABA (terbutaline) on
clinically relevant parameters associated with a reduction in work of breathing
or respiratory muscle fatigue in decompensated COPD patients admitted to the
ED.Forty consecutive decompensated COPD patients (having received at least one
dose of nebulized terbutaline during their stay in the ED) were included in an
observational cohort study. The terbutaline dose received at time t was expressed
as cumulative dose and as a rate (mg/day). The associations between the
terbutaline dose and time-dependent outcome parameters (respiratory rate, heart
rate, arterial blood gases, and, as a marker of terbutaline's systemic effect,
serum potassium) were analyzed using a nonlinear, mixed-effects model. The effect
of various covariates influencing terbutaline's effectiveness (baseline
characteristics and concomitant treatments) was assessed on the model.Among the
investigated patients, a total of 377 time-dependent observations were available
for analysis. Neither the cumulative dose nor the dose rate at time t
significantly influenced the arterial blood gas parameters or heart rate. The
cumulative dose of terbutaline was associated with a lower serum potassium level
(P < 0.001) and, less significantly, a lower respiratory frequency (P = 0.036).
In a tertile analysis, the need for post-ED hospitalization was not associated
with the cumulative dose or dose rate of terbutaline.Overall, the results of our
modeling study strongly suggest that terbutaline dose did not influence time
dependent outcomes other than serum potassium, and thus call into question the
systematic administration of inhaled SABA to patients admitted to the ED for
decompensated COPD.
PMID- 27512881
TI - Defining and validating comorbidities and procedures in ICD-10 health data in ST
elevation myocardial infarction patients.
AB - Administrative health databases are used in research to define comorbid
conditions, diagnosis, and procedures. Our objectives were to validate a
diagnosis of ST-elevation myocardial infarction (STEMI) and invasive cardiac
procedure coding against a comprehensive registry of STEMI patients and determine
an optimal algorithm for defining comorbidities using administrative
hospitalization and ambulatory databases, but without using a physician claims
database, which is unavailable for use in many jurisdictions.A registry of
consecutive STEMI patients was used to define a reference cohort and linked to
the hospitalization and ambulatory databases. Four administrative case
definitions for defining comorbidities, as well as STEMI diagnosis and in
hospital procedures using the International Classification of Diseases, 10th
Revision (ICD-10) and the Canadian Classification of Health Interventions (CCI)
were evaluated. Metrics were used to evaluate algorithm performance and compare
discriminative ability using the C statistic.The 3236 patients had median age of
60 years (interquartile range 52-71) and 75.7% were male. A diagnosis of STEMI
was correctly identified in the administrative records for 3043 (94.0%) patients.
In-hospital procedures (coronary artery bypass grafting, percutaneous coronary
intervention, and angiogram) were well identified using administrative
definitions (Kappa statistic 0.83-1.00). Validation of comorbidities varied by
condition but an algorithm using 2 inpatient/ambulatory visits in the previous 2
years maximized PPV, ranging from 28.6% for previous heart failure to 95.7% for
previous MI. The c statistic was similar for each of the methods, ranging from
0.76 to 0.80.ICD-10 and CCI codes can identify hospitalized STEMI patients with
high sensitivity and accurately define in-hospital cardiac procedures.
Comorbidities can be defined with high PPV using a definition of 2
inpatient/ambulatory visits in the previous 2 years.
PMID- 27512882
TI - The constellation of skeletal deformities in a family with mixed types of
mucopolysaccharidoses: Case report.
AB - INTRODUCTION: A 13-year-old child was clinically diagnosed with
mucopolysaccharidosis type VI-Maroteaux-Lamy syndrome (MPS VI) at the age of 5
years, and the diagnosis was confirmed biochemically and genetically (homozygous
mutation in ARSB gene). At that time, his older brother manifested with
increasing severe mental retardation. His urinary glycosaminoglycan excretion in
urine was elevated, but there was only 1 mutation in the ARSB gene defining him
as a healthy carrier of MPS VI. The 15-year-old boy was born with dysmorphic
facial features, cleft lip and palate, and multiple contractures associated with
profound skeletal deformities manifested, severe mental retardation, and
seizures, leading to the diagnosis of cerebral palsy from birth on.Clinical and
radiographic phenotypic characterization was the baseline tool to document the
older sibling, parents, and relatives, all of them examined at the Orthopaedic
Hospital of Speising, Vienna, Austria. The family history (from maternal and
paternal sides) showed >10 subjects with variable clinical histories of
hyperactivity and attention deficit disorder, depression, and a diversity of
skeletal abnormalities, such as dysplastic spondylolisthesis, discovertebral
degeneration, osteopenia, osteophytosis, and progressive degeneration of the
weight bearing zones (mostly developed at middle age). METHODS: Eleven patients
in a family with interrelated marriages (two male siblings of 15 and 13-year
old), parents and relatives over three generations were enrolled. One of the
siblings was diagnosed with Maroteaux-Lamy syndrome at the age of five-years and
mutation of the ARBS gene has been encountered. The older sibling manifested at
birth craniofacial abnormalities associated with multiple contracture and
seizures. Cerebral palsy was the suggested diagnosis. Clinical and radiographic
phenotypes were the baseline tool to document the older sibling, parents and
relatives at the orthopaedic Hospital of Speising, Vienna, Austria. These were
followed by whole Exome sequencing in three family subjects. RESULTS: A series of
genetic studies in the older sibling showed homozygous mutation in GNS gene
compatible with MPS IIID. Both parents are first related and were found to be
heterozygous for N-acetylglucosamine-6-sulfatase GNS gene. Family history showed
more than 10 subjects with variable clinical presentations such as dysplastic
spondylolisthesis, disco-vertebral degeneration, osteopenia, osteophytosis, and
progressive degeneration of the weight bearing zones (mostly developed at middle
age). CONCLUSION: Owing to the multiple systemic involvements, a genetic cause
was suspected and a molecular genetic investigation by using whole-exome
sequencing method in 3 family subjects (trios) was performed: the 15-year-old boy
and his parents. A homozygous splice-site-mutation in the GNS gene could be
found, compatible with mucopolysaccharidosis-Sanfillipo syndrome (type IIID).
Both parents are first related and were now found also to be heterozygous for the
GNS gene mutation found in their older son. Therefore, both parents are
heterozygous carriers for the ARSB gene mutation but also the GNS gene mutation.
In the son with MPS VI, no mutation in the GNS gene was found, but the brother
with MPS IIID was heterozygous for the ARSB gene mutation.We presume that the
intrafamilial variability of clinical signs in different family members could be
the result of various mutations in the ARSB/GNS genes in the carriers or
potential modulating effects of other genes or differences in genetic
backgrounds.
PMID- 27512883
TI - Smoking habits and benign prostatic hyperplasia: A systematic review and meta
analysis of observational studies.
AB - Previous studies have warned against the promoting effects of cigarette smoking
on benign prostatic hyperplasia (BPH). In contrast, some have argued that smoking
confers a protective effect regarding BPH, while others have observed an
aggravated effect. Thus, we performed this meta-analysis to determine whether
cigarette use is associated with BPH risk.To identify articles from observational
studies of relevance, a search was performed concurrent to March 21, 2016, on
PubMed, Web of Science, Cochrane, EBSCO, and EMBASE databases. Random-effect
model, according to the heterogeneity, was calculated to reveal the relative
risks (RRs) and corresponding 95% confidence intervals (CIs).Eight articles were
included in this meta-analysis, representing data for 44,100 subjects, of which
5221 (11.8%) had BPH as defined according to the criteria. Seven reports are
concerned with analysis between nonsmokers and ex-smokers, in which no
significant difference was observed (RR = 0.99, 95% CI 0.94-1.05). Another meta
analysis of 7 studies indicated an observable trend, but without significant
difference between groups of nonsmokers and current smokers (RR = 1.17, 95% CI
0.98-1.41). Between groups of heavy (6 articles; RR = 1.02, 95% CI 0.84-1.24) and
light smokers (5 articles; RR = 0.90, 95% CI 0.71-1.15), again no significant
difference appears. Finally, we combined individuals as never-smokers and ever
smokers and still found no significant difference between the 2 groups of
patients (RR = 1.03, 95% CI 0.92-1.15). Sensitivity analysis was displayed and
confirmed the stability of the present results.Combined evidence from
observational studies shows no significant association between cigarette smoking
and BPH risk, either for ex-smokers or for current smokers. The trend of elevated
BPH risk from smoking was observed only in current smokers compared with
nonsmokers, while marginal significance was observed in comparing ever-smokers
with never-smokers in operative patients with BPH.
PMID- 27512884
TI - Risk factors for pulmonary complications following laparoscopic gastrectomy: A
single-center study.
AB - The risk factors associated with postoperative pulmonary complications (PPCs)
following laparoscopic gastrectomy have not been well studied. We sought to
identify the risk factors for PPCs following gastric cancer surgery.A
retrospective analysis was performed on all gastric cancer patients in a
prospective database who underwent a laparoscopic gastrectomy from 2004 to 2014.
The potential risk factors for PPCs were evaluated.PPCs occurred in 6.8%
(83/1205) of patients and included pneumonia in 56 (67.5%) patients, pleural
effusion in 26 (31.3%) patients, and pulmonary embolism in 1 (1.2%) patient. The
multivariate analysis identified the following significant risk factors for PPCs:
advanced age (odds ratio [OR] = 1.043, 95% confidence interval [CI] = 1.021%,
1.066%), chronic obstructive pulmonary disease (COPD) (OR = 17.788, 95% CI =
2.618%, 120.838%), total gastrectomy (OR = 2.781, 95% CI = 1.726%, 4.480%), time
to first diet (OR = 1.175, 95% CI = 1.060%, 1.302%), and postoperative hospital
stay (OR = 1.015, 95% CI = 1.002%, 1.028%). The risk factors for pneumonia
included advanced age (OR = 1.036, 95% CI = 1.010%, 1.063%), total gastrectomy
(OR = 3.420, 95% CI = 1.960%, 5.969%), and time to first diet (OR = 1.207, 95% CI
= 1.703%, 1.358%). Only pancreatectomy was a risk factor for pleural effusion (OR
= 9.082, 95% CI = 2.412%, 34.206%).The frequency of PPCs in patients with gastric
cancer who underwent laparoscopic surgery was relatively high. Patients with
cardiac and pulmonary comorbidities and those who undergo total gastrectomy and
combined resection should be considered at high risk.
PMID- 27512885
TI - Elevated CD8 T-cell counts and virological failure in HIV-infected patients after
combination antiretroviral therapy.
AB - Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may
be an early warning indicator for future treatment failure. Thus, we investigated
whether elevated CD8 counts were associated with virological failure (VF) in the
first 4 years of cART in Asian HIV-infected patients in a multicenter regional
cohort.We included patients from the TREAT Asia HIV Observational Database
(TAHOD). Patients were included in the analysis if they started cART between 1996
and 2013 with at least one CD8 measurement within 6 months prior to cART
initiation and at least one CD8 and viral load (VL) measurement beyond 6 months
after starting cART. We defined VF as VL >=400 copies/mL after 6 months on cART.
Elevated CD8 was defined as CD8 >=1200 cells/MUL. Time to VF was modeled using
Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites
were included in this analysis, of whom 665 (27%) experienced VF in the first 4
years of cART. The overall rate of VF was 12.95 per 100 person-years. In the
multivariate model, the most recent elevated CD8 was significantly associated
with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However,
the sensitivity analysis showed that time-lagged CD8 measured at least 6 months
prior to our virological endpoint was not statistically significant (P =
0.420).This study indicates that the relationship between the most recent CD8
count and VF was possibly due to the CD8 cells reacting to the increase in VL
rather than causing the VL increase itself. However, CD8 levels may be a useful
indicator for VF in HIV-infected patients after starting cART.
PMID- 27512886
TI - Effect of extracorporeal shock wave therapy on scar pain in burn patients: A
prospective, randomized, single-blind, placebo-controlled study.
AB - BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been used to reduce pain
in patients with various musculoskeletal diseases and wounds. We investigated the
effect of ESWT on scar pain after complete wound epithelialization in burn
patients. METHODS: A prospective, single-blind, placebo-controlled study was
conducted from February 2014 to 2015. Forty patients with burn scar pain despite
standard therapy (medication, physical therapy, and burn rehabilitation massage
therapy) were randomized into ESWT or control (sham ESWT) groups. ESWT was
administered at 100 impulses/cm (0.05-0.15 mJ/mm) once per week for 3 weeks. The
treatment effects were assessed using the numerical rating scale (NRS), pain
threshold, Nirschl pain phase system, and Roles and Maudsley scores. RESULTS: The
characteristics of patients between the 2 study groups were balanced (P >0.05)
for age, sex, and total burn surface area (%). In both groups, the NRS, pain
threshold (Ib/cm), and Nirschl pain phase system values significantly improved (P
<0.05) after 3 sessions of ESWT or sham therapy, and there were significant
differences between the 2 groups in terms of these 3 variables (P <0.001, P
<0.001, P = 0.013, respectively). The Roles and Maudsley scores significantly
improved; among 20 patients, 17 reported a score of poor (85%) and 3 reported
fair (15%) before ESWT, whereas 3 reported poor (15%), 8 reported fair (40%), 5
reported good (25%), and 4 reported excellent (20%) after ESWT (P = 0.004). The
scores did not improve in the control group (P = 0.128). CONCLUSION: ESWT
significantly reduced scar pain in burn patients after wound recovery.
PMID- 27512887
TI - Efficacy of continuous epidural block in acute herpes zoster: Incidence and
predictive factors of postherpetic neuralgia, a retrospective single-center
study.
AB - The aim of the present study was to investigate efficacy of continuous epidural
block for prevent postherpetic neuralgia (PHN) progression in cases of acute
herpes zoster with severe pain and also to identify predictive factors for PHN in
such conditions.We retrospectively analyzed the clinical data of patients with
herpes zoster who underwent continuous epidural block between March 2013 and
October 2015. Time points were set as 1 month, 3 months, and 6 months after
zoster onset. PHN was defined as the presence of pain with NRS >=3 at certain
time points.The incidence of developing PHN was 38.1%, 27.0%, and 19.0% 1 month,
3 months, and 6 months after zoster onset, respectively. Age and duration of
catheterization were predictive factors for PHN at 1 month. Age, duration of
catheterization, and NRS at first visit were identified as predictive factors for
PHN at 3 months. Presence of diabetes, duration of catheterization, and NRS
during catheterization were significant predictive factors for PHN at 6
months.The incidence of PHN is higher in zoster patients with severe pain that
requires continuous epidural block compared to incidence in the general
population. Advanced age and severe initial pain intensity were predictive
factors of PHN development. Prolonged catheterization resulting from weak
response to treatment strongly suggested progression to PHN.
PMID- 27512888
TI - Clinical significance of No. 10 and 11 lymph nodes posterior to the splenic
vessel in D2 radical total gastrectomy: An observational study.
AB - D2 lymphadenectomy is widely performed for advanced proximal gastric cancer, but
complete dissection of No. 10 and 11 lymph nodes (LNs) is technically
challenging, especially for those posterior to the splenic vessel. This study
aimed to investigate the clinical significance of removing No. 10 and 11 LNs
posterior to the splenic vessel in radical total gastrectomy. Between January
2013 and February 2015, 53 patients who underwent spleen-preserving D2 radical
total gastrectomy were enrolled. While dissecting No. 10 and 11 LNs, we divided
them into 2 parts, namely LNs anterosuperior and posterior to the splenic vessel,
and the pathological data were reviewed. Sixteen patients underwent laparoscopy
and 37 underwent laparotomy. No mortality was recorded. According to the
pathological results, the TNM stages of the tumor were IIA in 11 patients
(20.8%), IIB in 5 (9.4%), IIIA in 7 (13.2%), IIIB in 10 (18.9%), and IIIC in 20
(18.9%). The mean number of LNs retrieved was 30.3 +/- 12.3. The sum of No. 10
and 11 LNs posterior to the splenic vessel was 59 and the mean number was 1.11 +/
1.47. One LN with metastasis was found in the special 59 regional LNs, and the
metastasis rate was 1.9% (1/53). Concerning the low metastasis rate (1.9%) and
difficult complete dissection of No. 10 and 11 LNs posterior to the splenic
vessel, our initial analysis suggests that the rate of No. 10 and 11 LNs
posterior to the splenic vessel metastasis was 1.9%, but further studies are
needed to reveal its clinical significance in D2 radical total gastrectomy for
advanced proximal gastric cancer.
PMID- 27512889
TI - Cancer in first-degree relatives of people with celiac disease.
AB - BACKGROUND: Celiac disease (CD) has been linked to cancer, especially
lymphoproliferative malignancy (LPM). Earlier research has shown that first
degree relatives (FDRs) to individuals with CD are at increased risk of
autoimmunity including CD, but data on their risk of cancer are scarce and
contradictory. We aimed to assess whether Swedish FDRs to individuals with CD are
at increased risk of cancer. METHODS: Individuals with CD (identified through
biopsy reports equal to Marsh grade III) were matched on sex, age, county, and
calendar year with up to 5 control individuals. All FDRs (father, mother,
sibling, offspring) of CD individuals ("celiac FDRs": n = 109,391) and controls
(n = 548,465) were identified through Swedish healthcare registries. Through Cox
regression, we calculated hazard ratios (HRs) for cancer incidence (all cancer,
breast cancer, gastrointestinal cancer, and LPM). RESULTS: During follow-up,
celiac FDRs experienced 10,750 unique cancers as opposed to 54,686 in-control
FDRs. Celiac FDRs were at a slightly lower risk of any cancer (HR 0.97, 95%
confidence interval [CI] 0.95-0.99), partially due to the lower risk of breast
cancer (HR 0.92, 95% CI 0.87-0.98). The relative risks of LPM (HR 0.99, 95% CI
0.91-1.08) and gastrointestinal cancer (HR 0.98, 95%CI 0.93-1.03) were both close
to 1. As opposed to earlier research, we found no excess risk of LPM in siblings
to individuals with CD (HR 0.98, 95% CI 0.81-1.19). CONCLUSION: Celiac FDRs are
not at increased risk of cancer, including LPM, arguing that shared genetics is
unlikely to explain previous reports of an excess risk of LPM in patients with
CD.
PMID- 27512890
TI - A 10-year follow-up study of the association between calcium channel blocker use
and the risk of dementia in elderly hypertensive patients.
AB - Calcium channel blockers (CCBs) are widely used for reducing blood pressure of
hypertensive patients. Recent reports document the beneficial effects of CCB for
preventing dementia; however, the results are controversial. We aim to evaluate
the risk of developing dementia among elderly hypertensive patients treated with
CCB.We designed a retrospective population-based cohort study using the records
of the National Health Insurance Research Database of Taiwan dated from 2000 to
2010. The study cohort comprised 82,107 hypertensive patients of more than 60
years of age, and 4004 propensity score (PS)-matched pairs were selected
according to age, sex, year of hypertension diagnosis, and baseline
comorbidities. We employed a robust Cox proportional hazard model to estimate the
hazard ratio (HR) of developing dementia in the PS-matched cohort.The annual
incidence of dementia in the CCB-exposure group was significantly lower than that
in the comparator group (3.9 vs 6.9 per 1000 person-years, P < 0.01) during the
follow-up period (4.4 +/- 2.5 years). Based on the PS-matched cohort, the
adjusted HR of dementia in the CCB-exposure group was significantly lower than
that in comparator group (HR = 0.53, 95% confidence interval: 0.39-0.72, P <
0.01). Sensitivity and subgroup analyses also confirmed similar findings.Our
results provided evidence for an association between CCB use and a lower risk of
developing dementia among the elderly hypertensive patients. Further studies are
required to explore the causal relationship between CCB use and dementia.
PMID- 27512891
TI - Topical Antimicrobials and the Open Surgical Wound.
AB - BACKGROUND: Topical antiseptic and antibiotic agents have been used for the
prevention of surgical site infections since Joseph Lister's original research on
this subject. Although these agents are used extensively in clinical practice,
evidence to support the use of topical antimicrobial agents remains limited.
PATIENTS AND METHODS: The world literature on the use of antiseptic and
antibiotic agents was evaluated to determine the current status of evidence to
support the use of topical antimicrobial agents in the prevention of surgical
site infections. RESULTS: Although several techniques of using topical antibiotic
solutions, powders, antibiotic gauzes, and beads have some evidence for
validation, there are equal numbers of reports that have failed to show benefit.
There is little evidence to support the use of antiseptic solutions in the
prevention of infections at the surgical site. CONCLUSIONS: Additional clinical
trials are necessary to provide evidence to support any of the methods for using
topical antimicrobial agents to present surgical site infections. Dilute
antiseptic agents should be considered in future trials when antimicrobial
activity can be identified without local toxicity.
PMID- 27512893
TI - Widespread copper and lead contamination of household drinking water, New South
Wales, Australia.
AB - This study examines arsenic, copper, lead and manganese drinking water
contamination at the domestic consumer's kitchen tap in homes of New South Wales,
Australia. Analysis of 212 first draw drinking water samples shows that almost
100% and 56% of samples contain detectable concentrations of copper and lead,
respectively. Of these detectable concentrations, copper exceeds Australian
Drinking Water Guidelines (ADWG) in 5% of samples and lead in 8%. By contrast, no
samples contained arsenic and manganese water concentrations in excess of the
ADWG. Analysis of household plumbing fittings (taps and connecting pipework) show
that these are a significant source of drinking water lead contamination. Water
lead concentrations derived for plumbing components range from 108ug/L to
1440ug/L (n=28, mean - 328ug/L, median - 225ug/L). Analysis of kitchen tap
fittings demonstrates these are a primary source of drinking water lead
contamination (n=9, mean - 63.4ug/L, median - 59.0ug/L). The results of this
study demonstrate that along with other potential sources of contamination in
households, plumbing products that contain detectable lead up to 2.84% are
contributing to contamination of household drinking water. Given that both copper
and lead are known to cause significant health detriments, products for use in
contact with drinking water should be manufactured free from copper and lead.
PMID- 27512894
TI - A Virus-Mimicking, Endosomolytic Liposomal System for Efficient, pH-Triggered
Intracellular Drug Delivery.
AB - A novel multifunctional liposomal delivery platform has been developed to
resemble the structural and functional traits of an influenza virus. Novel
pseudopeptides were prepared to mimic the pH-responsive endosomolytic behavior of
influenza viral peptides through grafting a hydrophobic amino acid, l
phenylalanine, onto the backbone of a polyamide, poly(l-lysine isophthalamide),
at various degrees of substitution. These pseudopeptidic polymers were employed
to functionalize the surface of cholesterol-containing liposomes that mimic the
viral envelope. By controlling the cholesterol proportion as well as the
concentration and amphiphilicity of the pseudopeptides, the entire payload was
rapidly released at endosomal pHs, while there was no release at pH 7.4. A pH
triggered, reversible change in liposomal size was observed, and the release
mechanism was elucidated. In addition, the virus-mimicking nanostructures
efficiently disrupted the erythrocyte membrane at pH 6.5 characteristic of early
endosomes, while they showed negligible cytotoxic effects at physiological pH.
The efficient intracellular delivery of the widely used anticancer drug
doxorubicin (DOX) by the multifunctional liposomes was demonstrated, leading to
significantly increased potency against HeLa cancer cells over the DOX-loaded
bare liposomes. This novel virus-mimicking liposomal system, with the
incorporated synergy of efficient liposomal drug release and efficient endosomal
escape, is favorable for efficient intracellular drug delivery.
PMID- 27512895
TI - Pore Size Effect on Methane Adsorption in Mesoporous Silica Materials Studied by
Small-Angle Neutron Scattering.
AB - Methane adsorption in model mesoporous silica materials with the size range
characteristic of shale is studied by small-angle neutron scattering (SANS). Size
effect on the temperature-dependent gas adsorption at methane pressure about 100
kPa is investigated by SANS using MCM-41 and SBA-15 as adsorbents. Above the gas
liquid condensation temperature, the thickness of the adsorption layer is found
to be roughly constant as a function of the temperature. Moreover, the gas
adsorption properties, such as the adsorbed layer thickness and the specific
amount of adsorbed gas, have little dependence on the pore size being studied,
i.e., pore radius of 16.5 and 34.1 A, but are mainly affected by the roughness of
the pore surfaces. Hence, the surface properties of the pore wall are more
dominant than the pore size in determining the methane gas adsorption of pores at
the nanometer size range. Not surprisingly, the gas-liquid condensation
temperature is observed to be sensitive to pore size and shifts to higher
temperature when the pore size is smaller. Below the gas-liquid condensation
temperature, even though the majority of gas adsorption experiments/simulations
have assumed the density of confined liquid to be the same as the bulk density,
the measured methane mass density in our samples is found to be appreciably
smaller than the bulk methane density regardless of the pore sizes studied here.
The mass density of liquid/solid methane in pores with different sizes shows
different temperature dependence below the condensation temperature. With
decreasing temperature, the methane density in larger pores (SBA-15) abruptly
increases at approximately 65 K and then plateaus. In contrast, the density in
smaller pores (MCM-41) monotonically increases with decreasing temperature before
reaching a plateau at approximately 30 K.
PMID- 27512896
TI - Polyamines: Small Molecules with a Big Role in Promoting Virus Infection.
AB - Polyamines play important roles in a range of cellular processes. In this issue
of Cell Host & Microbe, Mounce et al. (2016) link polyamine metabolism to the
interferon response and demonstrate proviral effects for polyamines. The study
points to the pathway as a potential novel pan-viral therapeutic target.
PMID- 27512897
TI - When Mr. Fap Meets the Gals.
AB - Fusobacteria are found to be overrepresented in the colorectal tumor
microenvironment. In this issue of Cell Host & Microbe, Abed et al. (2016)
describe a novel homing mechanism by which fusobacteria localize to tumors by
recognizing a host polysaccharide (Gal-GalNAc) on cancer cells using a
fusobacterial lectin, Fap2.
PMID- 27512898
TI - Unhealthy Sugars in Bacterial Cytotoxicity.
AB - Bacterial type three secretion systems (T3SSs) are central to virulence, but the
processes stimulating their activation are unclear. In this issue of Cell Host &
Microbe, Blondel et al. (2016) perform a genome-wide screen using CRISPR/Cas
technology to identify a role for cell surface sulfation and fucosylation in
cytotoxicity mediated by Vibrio parahaemolyticus T3SSs.
PMID- 27512899
TI - Gut Check: IFNgamma Delays Mucosal Recovery during Antibiotic Therapy.
AB - Antibiotic therapy has been largely ineffective in improving clinical outcomes
following Salmonellosis, yet the reasons why remain obscure. In this issue of
Cell Host & Microbe, Dolowschiak et al. (2016) report that IFNgamma produced by
NK and T cells following antibiotic treatment of acute Salmonella infection
limits mucosal remission.
PMID- 27512900
TI - NAGging Hexokinase PEPs up NLRP3.
AB - Recognition of peptidoglycan is integral to detection of gram-positive bacterial
pathogens. In a recent issue of Cell, Wolf et al. (2016) report that detection of
the N-acetylglucosamine component of peptidoglycan by the glycolytic enzyme
hexokinase activates the NLRP3 inflammasome, revealing an intriguing interplay
between pathogen detection and metabolism.
PMID- 27512901
TI - Bacterial Stress Responses during Host Infection.
AB - Pathogenic bacteria must withstand diverse host environments during infection.
Environmental signals, such as pH, temperature, nutrient limitation, etc., not
only trigger adaptive responses within bacteria to these specific stress
conditions but also direct the expression of virulence genes at an appropriate
time and place. An appreciation of stress responses and their regulation is
therefore essential for an understanding of bacterial pathogenesis. This review
considers specific stresses in the host environment and their relevance to
pathogenesis, with a particular focus on the enteric pathogen Salmonella.
PMID- 27512902
TI - Discrimination and Integration of Stress Signals by Pathogenic Bacteria.
AB - For pathogenic bacteria, the ability to sense and respond to environmental
stresses encountered within the host is critically important, allowing them to
adapt to changing conditions and express virulence genes appropriately. This
review considers the diverse molecular mechanisms by which stress conditions are
sensed by bacteria, how related signals are discriminated, and how stress
responses are integrated, highlighting recent studies in selected bacterial
pathogens of clinical relevance.
PMID- 27512903
TI - An Intrinsically Disordered Region of the DNA Repair Protein Nbs1 Is a Species
Specific Barrier to Herpes Simplex Virus 1 in Primates.
AB - Humans occasionally transmit herpes simplex virus 1 (HSV-1) to captive primates,
who reciprocally harbor alphaherpesviruses poised for zoonotic transmission to
humans. To understand the basis for the species-specific restriction of HSV-1 in
primates, we simulated what might happen during the cross-species transmission of
HSV-1 and found that the DNA repair protein Nbs1 from only some primate species
is able to promote HSV-1 infection. The Nbs1 homologs that promote HSV-1
infection also interact with the HSV-1 ICP0 protein. ICP0 interaction mapped to a
region of structural disorder in the Nbs1 protein. Chimeras reversing patterns of
disorder in Nbs1 reversed titers of HSV-1 produced in the cell. By extending this
analysis to 1,237 virus-interacting mammalian proteins, we show that proteins
that interact with viruses are highly enriched in disorder, suggesting that
viruses commonly interact with host proteins through intrinsically disordered
domains.
PMID- 27512906
TI - Plant TRAF Proteins Regulate NLR Immune Receptor Turnover.
PMID- 27512904
TI - Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by
Binding to Tumor-Expressed Gal-GalNAc.
AB - Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic
tumor formation in preclinical models. However, fusobacteria are core members of
the human oral microbiome and less prevalent in the healthy gut, raising
questions about how fusobacteria localize to CRC. We identify a host
polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in
CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial
Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical
adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O
glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or
inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells
and established CRCs in mice. Additionally, intravenously injected F. nucleatum
localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that
fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus,
targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria
potentiation of CRC.
PMID- 27512907
TI - Magnetic properties of transition metal Mn, Fe and Co dimers on monolayer
phosphorene.
AB - We studied the geometries, electronic structure and magnetic properties of
substitutional doping and adsorption of transition metal (Mn, Fe and Co) dimers
on phosphorene monolayer in the framework of the generalized gradient
approximation (GGA) and GGA + U. Electronic band structures and magnetic
properties were dependent on the doping type and dopant materials. For Mn and Fe
substitutional and adsorption dimers, we obtained semiconducting band structures
with spin polarization. However, we found a half-metallic feature in Co
substitutional dimer while the Co adsorption dimer showed a semiconducting
behavior without any spin polarization. With GGA + U, all the systems showed spin
polarized semiconducting band structures except Co adsorption dimer which
remained unaffected. The hybridization between transition metal (TM) and
phosphorene sheet contributed to suppressing the magnetic moment of TM dimers.
For instance, the total magnetic moments of -2.0, 4.24 and 1.28 MU B/cell for Mn,
Fe and Co substitutional dimers were obtained while the Mn and Fe adsorption
dimers showed magnetic moments of -1.69 and 0.46 MU B/cell. These magnetic
moments were enhanced with GGA + U. The same magnetic ground states were obtained
both from GGA and GGA + U approaches except for the Mn dimers. We observed that
the Mn and Fe substitutional dimers showed an out-of-plane magnetization while an
in-plane magnetization was observed in Co substitutional dimer. The Mn adsorption
dimer still displayed a perpendicular magnetization whereas the Fe adsorption
dimer had an in-plane magnetization. We found that the both GGA and GGA + U
showed the same magnetization direction in all the systems.
PMID- 27512905
TI - Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of
Tuberculous Infection In Vivo.
AB - The blockade of phagolysosomal fusion is considered a critical mycobacterial
strategy to survive in macrophages. However, viable mycobacteria have been
observed in phagolysosomes during infection of cultured macrophages, and
mycobacteria have the virulence determinant MarP, which confers acid resistance
in vitro. Here we show in mice and zebrafish that innate macrophages overcome
mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial
proportion of infecting bacteria to phagolysosomes. Exploiting the optical
transparency of the zebrafish, we tracked the fates of individual mycobacteria
delivered to phagosomes versus phagolysosomes and discovered that bacteria
survive and grow in phagolysosomes, though growth is slower. MarP is required
specifically for phagolysosomal survival, making it an important determinant for
the establishment of mycobacterial infection in their hosts. Our work suggests
that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they
tolerate the resulting acidic environment of the phagolysosome to establish
infection.
PMID- 27512909
TI - Iatrogenic common bile duct injuries: Increasing complexity in the laparoscopic
era: A prospective cohort study.
AB - PURPOSE: Iatrogenic bile duct injury (BDI) is the most significant associated
complication to laparoscopic cholecystectomy (LC). Little is known about the
evolution of the pattern of BDI in the era of laparoscopy. The aim of the study
is to assess the pattern of post-LC BDIs managed in a tertiary referral centre.
METHODS: Post-LC BDI referred over two decades were studied. Demographic data,
type of BDI (classified using the Strasberg System), clinical symptoms,
diagnostic investigations, timing of referral, post-referral management and
morbidity were analysed. The pattern of injury, associated vascular injuries rate
and their management were compared over two time periods (1992-2004,2005-2014).
RESULTS: 78 BDIs were referred. During the second time period Strasberg A
injuries decreased from 14% to 0 and Strasberg E1increased from 4% to 23%, the
rate of associated vascular injury was six time higher (3.6% versus 22.7%), more
patients had an attempted repair at the index hospital (16% versus 35%) sand
fewer patients could be managed without surgical intervention at the referral
hospital (28% versus 4%). CONCLUSION: Complexity of referred BDIs and rate of
associated vascular injuries have increased over time. These findings led to more
patients managed requiring surgical intervention at the referral hospital.
PMID- 27512910
TI - Viewers prefer predictive cues.
AB - Devaluation-by-inhibition hypothesis demonstrated that previously ignored items
are judged more negatively than previously attended and novel items. Based on
this view, the present study investigated the evaluation of preceding stimuli
that presumably elicit attentional processes to task-relevant stimuli.
Accordingly, we employed a Posner-type cueing task followed by evaluation of the
preceding cues indicating left and right directions. The important manipulation
is predictability of two different preceding cues which predict the target
location with high or with low probability. In Experiment 1 with two different
arrows, a low predictive arrow was judged more negatively than a high predictive
cue. Experiment 2 using gaze cues of two persons instead of two different arrows
supported the findings of Experiment 1. These findings are consistent with
devaluation-by-inhibition, suggesting that cue items triggering attention to the
target are devaluated when they have less predictability.
PMID- 27512911
TI - RE16AuxAl13-x with RE = La-Nd, Sm (x<= 3.37): synthesis, crystal structure and
physical properties of an intermetallic solid solution with barrelane analogue
units.
AB - During phase analytical investigations in the rare-earth element rich side of the
ternary system cerium-gold-aluminum, the new ternary rare-earth (RE) gold
aluminides with a composition of RE16AuxAl13-x (RE = La-Nd, Sm, x<= 3.37) have
been synthesized first by reactive eutectics of RE/Au with Al. Single crystals of
high quality can be obtained by this method. The title compounds can be
selectively prepared by annealing arc-melted beads of appropriate composition
below the peritectic point of the respective system. Like prototypic La16Al13,
the representatives of the solid solution RE16AuxAl13-x (RE = La-Nd, Sm; x<=
3.37) crystallize in the hexagonal crystal system (space group P6[combining
macron]2m, a = 916.6-890.4 pm, c = 1122.4-1090.1 pm) with one formula unit per
unit cell. Single crystal investigations revealed Au/Al mixing on three of the
four crystallographic aluminum sites. These sites form an empty (Au/Al)11
barrelane analogous unit, coordinated solely by the respective rare-earth atoms.
In addition one independent Al site with a fivefold capped trigonal prismatic
arrangement, a so called Edshammar polyhedron, exists. Magnetic measurements of
Ce16Au3Al10 revealed two antiferromagnetic transitions with Neel-temperatures of
7.7(1) and 2.7(1) K and a magnetic moment of MUeff = 2.48(1) MUB, Pr16Au3Al10
shows ferromagentic ordering with a Curie-temperature of 19.8(1) K and a magnetic
moment of MUeff = 3.58(1) MUB.
PMID- 27512913
TI - Effect of antidepressants on spatial memory deficit induced by dizocilpine.
AB - Cognitive deficits are a core symptom of schizophrenia. It is controversial
whether antidepressants could improve cognitive symptoms in schizophrenia
patients. The present study was designed to identify the therapeutic effect of
antidepressants on cognitive deficits in schizophrenia. In the present study,
adolescent rats were repeatedly exposed to dizocilpine, which can induce
cognitive deficits associated with schizophrenia. Then these rats were treated by
six antidepressants (fluvoxamine, sertraline, paroxetine, escitalopram,
venlafaxine, mirtazapine) or vehicle. The rats in the control group were exposed
to vehicle during the study. Lastly, all rats' spatial memory (a major part of
cognition) was assessed using the Morris water maze (MWM) test, and the density
of hippocampal parvalbumin (PV) interneurons was evaluated to explore possible
mechanisms underlying spatial memory change in schizophrenia. The results of the
present study supported the hypothesis of a therapeutic effect of fluvoxamine and
escitalopram on spatial memory deficit induced by dizocilpine. Additionally, the
data of the present study suggested that fluvoxamine and escitalopram remitted
hippocampal PV interneuron reduction induced by dizocilpine. The neuroprotective
effect of fluvoxamine and escitalopram may partly explain the therapeutic effect
of antidepressants on spatial memory deficit in schizophrenia patients.
PMID- 27512914
TI - Palate size and shape in schizophrenia.
AB - The palate is considered typical of the structures in which schizophrenia-related
minor physical anomalies may occur. In this study, we aimed to compare the
dimensions and form of palate in patients with schizophrenia with nonpsychiatric
controls in a blinded manner. Dental stone casts of 127 patients with
schizophrenia and 127 controls were prepared from impressions of the maxillary
dental arch. Palate dimensions were measured on the stone casts using a digital
caliper and palatometer. Palate length did not differ significantly between the
groups, but there was a significant difference in palate width and depth, which
were significantly higher in the schizophrenia group. As a result of using
multivariate analysis for assessing independent risk factors affecting patients
with schizophrenia, furrowed palate shape, palate width, and ellipsoid maxillary
dental arch shape were found to be significant. This study also revealed that
patients with schizophrenia demonstrate certain gender-related predilections in
the differences of palate parameters compared to same-sex controls. As the palate
develops in conjunction with both the face and brain, our study findings can
significantly contribute to the assumption that there might be structural
abnormalities of the palate that could represent specific markers of
embryological dysmorphogenesis underlying schizophrenia.
PMID- 27512915
TI - Effects of state and trait anxiety on sleep structure: A polysomnographic study
in 1083 subjects.
AB - Anxiety affects millions of people and has been shown to co-occur in combination
with sleep disturbances, generating heavy medical costs and a huge socio-medico
economic burden. Sleep-studies in anxiety disorders are inconsistent and the
effects of state and trait anxiety are unexplored. We selected 1083 patients from
the database of a hospital sleep laboratory. The patients had polysomnography for
different sleep disorders; their sleep initiation (sleep onset latency), sleep
maintenance (total sleep time), non-rapid eye movement sleep-, and rapid eye
movement sleep parameters; as well as their State-Trait Anxiety Inventory and
Beck depression scale were measured. In order to be included in our study,
individuals needed to score in the low or high range on the State and/or Trait
Subscales of the State-Trait Anxiety Inventory. We found that both state and
trait anxiety affected non-rapid eye movement sleep parameters. Sleep onset
latency changes predominantly associated to state anxiety while rapid eye
movement parameters related to trait anxiety.
PMID- 27512916
TI - Evaluating the association between the SHANK3 gene and bipolar disorder.
AB - BACKGROUND: Previous studies have shown that the genes involved in synaptic
density and plasticity were downregulated in bipolar disorder (BD) postmortem
brains. The SHANK3 (SH3 and multiple ankyrin repeat domain 3) protein is a
scaffold protein enriched in the postsynaptic density of excitatory synapses, and
recent findings were suggestive of a possible role of SHANK3 in the development
of BD. In this study, we aimed to evaluate the genetic association between the
gene encoding SHANK3 (SHANK3) and BD in Han Chinese. METHODS: Ten variants in
SHANK3 were genotyped among 1482 individuals with or without BD. We measured the
mRNA expression level of SHANK3 in patients with BD and controls. We then
performed an eQTL analysis. RESULTS: In our sample set, there were no significant
differences in allele, genotype and haplotype frequencies between the BD and
control groups. Our results showed no significant difference in the level of
peripheral SHANK3 expression between the BD patients and healthy controls.
Further eQTL analysis showed that rs9616915 has functional effect on SHANK3
expression in the hippocampus. CONCLUSION: This study does not provide evidence
for a major role of SHANK3 in the pathogenesis of BD.
PMID- 27512917
TI - The optimisation of experience sampling protocols in people with schizophrenia.
AB - Experience sampling methodology (ESM) involves completing questionnaires during
daily life and has been used extensively in people with schizophrenia to assess
symptoms and behaviours. Despite considerable advantages over interview measures,
there is limited information about its external validity. Our aim is to
investigate whether ESM protocol implementation is affected differentially in
people with schizophrenia and healthy individuals by factors such as mood,
medication and symptoms which would have implications for validity. Fifty-three
people with schizophrenia and fifty-eight controls from the general population
completed seven ESM questionnaires per day for six consecutive days. Compliance
and acceptability, including overall experience, training and disruption of
normal routines, were recorded. Overall questionnaire completion rate in people
with schizophrenia was comparable to controls (i.e. over 70%). People with
schizophrenia completed significantly fewer questionnaires in the morning but did
not show fatigue effects over the experience sampling period. Excluding
questionnaires in the morning did not significantly alter the findings. In the
schizophrenia group medication level and symptoms did not influence adherence.
However, higher disruption was associated with reduced questionnaire completion
in this group. These findings suggest that minimising disruption may enhance
validity and completion rates. ESM is a valid methodology to use with people with
schizophrenia.
PMID- 27512918
TI - Examining the role of self-discrepancy and self-directed style in bulimia
nervosa.
AB - Two of the primary components within Integrative Cognitive Affective Therapy
(ICAT) are self-discrepancy and self-directed style. Self-discrepancy includes
both actual:ideal (discrepancy between oneself and who one wishes they were) and
actual:ought (discrepancy between oneself and who one believes they ought to be).
Self-directed style in ICAT refers to a variety of behaviors emitted by a person
toward the self including self-blaming and self-affirming. This study explored
main effects and interactions between self-discrepancy and self-directed style in
relation to global eating disorder (ED) psychopathology, depressive symptoms, and
anxiety. Eighty treatment-seeking adults from the Midwest with BN or subthreshold
BN completed interviews and self-report measures. Self-affirm and self-blame were
associated with ED psychopathology, depressive symptoms, and anxiety.
Actual:ideal discrepancy was related to anxiety and actual:ought discrepancy was
related to anxiety and depressive symptoms. Interactions were found between self
affirm and actual:ought discrepancy as well as self-blame and actual:ought
discrepancy for depressive symptoms. High actual:ought was related to increased
depressive symptoms regardless of levels of self-affirm or self-blame. Effect
sizes for models were medium-to-large with anxiety models demonstrating the
largest effects. This study provides further evidence supporting the ICAT model
and treatment, which targets self-discrepancies, self-directed styles, and
related emotional states.
PMID- 27512919
TI - Altered plasma levels of chemokines in autism and their association with social
behaviors.
AB - Autism Spectrum Disorder (ASD) is a group of neurodevelopment disorders with an
unclear etiology. Chemokines have been implicated in the etiology and
pathogenesis of ASD. The current study investigated the plasma levels of seven
chemokines (RANTES, Eotaxin, MIP-1 alpha, MIP-1 beta, MCP-1, IP-10, and MIG) in
42 young autistic patients and 35 age-matched typically developing (TD) children.
The study also tested the association between these chemokine levels and social
behaviors, as measured by the Social Responsiveness Scale (SRS). Compared to the
TD children, RANTES, MIP-1alpha, and MIP-1beta were higher, while IP-10 and MIG
were lower in the autistic patients, after correcting for multiple comparisons.
Among these seven chemokines, MIP-1alpha, MIP-1beta and IP-10 levels were found
to be associated with social behaviors in all the participants. Moreover, MIP
1alpha and IP-10 were found to be independent predictors of social behaviors. The
results of our study support the hypothesis that altered chemokine levels are
involved in the pathophysiology of ASD and they indicate that chemokines plasma
levels could be potential biomarkers for ASD.
PMID- 27512920
TI - Apathy, alexithymia, and depressive symptoms: Points of convergence and
divergence.
AB - This study determined convergence and divergence in the constructs of
alexithymia, apathy, and depressive symptoms. Understanding of similarities and
differences between these constructs will improve diagnostic accuracy for
clinical and research purposes. Community-dwelling participants (N=622, M
age=35.6 years, SD=13.1) completed online measures of alexithymia, depression,
and apathy; 12.2% were alexithymic, 37.8% reported significant depressive
symptoms, and 24.9% reported significant apathy. Exploratory Factor Analyses
(EFAs) determined the best factor structure for the apathy, alexithymia, and
depressive symptoms was comprised of three factors and accounted for 45.1% of
item variance. The Depression, Apathy, and Alexithymia factors were defined most
strongly by item content that is at the core of each construct. Depression was
defined most highly by items assessing sadness, low self-esteem, and loneliness.
The strongest item loadings for Alexithymia were difficulty identifying and
describing feelings. Apathy was characterized by poor motivation, low interest,
and lack of initiative. However, each of these core and defining features had
significant cross-loadings on one of the other two factors. Negative affect
shared variance with Apathy, low motivation shared variance with Depression, and
difficulty describing and identify feelings shared variance with Depression and
Apathy. Clinical and research implications are discussed.
PMID- 27512921
TI - Serum levels of G protein-coupled estrogen receptor 1 (GPER1) in drug-naive
patients with generalized anxiety disorder.
AB - Sex hormones, particularly estrogen, are suggested to play a role in the
physiopathology of generalized anxiety disorder (GAD). Estrogen functions through
the estrogen receptors alpha and beta and the recently discovered G protein
coupled estrogen receptor 1 (GPER1). This study aimed, for the first time, to
evaluate serum GPER1 levels in drug-naive patients with GAD. This study included
40 newly diagnosed drug-naive patients with GAD aged between 18 and 50 years and
40 age- and gender-matched healthy controls. Medical histories were obtained, and
physical examinations and laboratory tests were conducted; the Hamilton Anxiety
Rating Scale (HAM-A) was also used for all participants. Serum GPER1 levels were
measured. The serum GPER1 level was significantly higher in the patients with GAD
than in the controls. A positive significant correlation was observed between the
GPER1 level and the HAM-A score. The receiver operating characteristic analysis
revealed a sensitivity, specificity, positive predictive value, and negative
predictive value of 85.0%, 82.5%, 82.9%, and 84.6%, respectively, for the
presence of anxiety when the serum GPER1 value was >=0.14 (the area under the
curve was 0.904.). In conclusion, this study demonstrated that GPER1 levels were
associated with the anxiety levels of patients, and that the serum GPER1 level
was a valuable predictor of the presence of anxiety independent of gender.
PMID- 27512922
TI - A preliminary analysis of microRNA-21 expression alteration after antipsychotic
treatment in patients with schizophrenia.
AB - Schizophrenia is a severe and debilitating psychiatric disorder of unknown
etiology, and its diagnosis is essentially based on clinical symptoms. Despite
growing evidence on the relation of altered expression of miRNAs and
schizophrenia, most patients with schizophrenia usually had an extensive
antipsychotic treatment history before miRNA expression profile analysis, and the
pharmacological effects on miRNA expression are largely unknown. To overcome
these impediments, miRNA microarray analysis was performed in peripheral blood
mononuclear cells (PBMCs) obtained from patients with schizophrenia who were not
on antipsychotic medication and healthy controls. Then, using quantitative real
time reverse transcription polymerase chain reaction (qRT-PCR), we verified the
top 10 miRNAs with the highest fold-change values from microarray analysis in 82
patients with schizophrenia and 43 healthy controls, and nine miRNAs demonstrated
significant differences in expression levels. Finally, we compared these nine
miRNA profiles before and after antipsychotic treatment. Our results revealed
that serum miR-21 expression decreased strikingly in patients after antipsychotic
treatment. The change of miR-21 expression was negatively correlated with
improvement of positive, general psychopathology, and aggressiveness symptoms.
This study preliminarily analyzed the possible changes in circulating miRNAs
expression in response to antipsychotic medication for schizophrenia, and the
molecular mechanisms of this needs to be further explored.
PMID- 27512923
TI - Three peanut-allergic/sensitized phenotypes with gender difference.
AB - BACKGROUND: Peanut-allergic reactions are heterogeneous ranging from mild
symptoms to anaphylaxis. OBJECTIVE: Identify peanut-allergic/sensitized
phenotypes to personalize patient management. METHODS: A combined factor and
cluster analysis was used to study the phenotypes of 696 patients diagnosed with
peanut sensitization and enrolled in the MIRABEL survey. The method was first
applied to the 247 patients with an oral food challenge (OFC). It was then
applied to the 449 patients without OFC to confirm the findings in an independent
population. RESULTS: Three independent clusters emerged from the OFC subgroup.
Cluster 1, 'Severe peanut allergy with little allergic multi-morbidity' (123
subjects), had the highest proportion of patients with positive OFC (92%), a
medium level of peanut protein inducing a positive OFC (235 mg), lower percentage
of allergic multi-morbidity (2% asthma plus atopic dermatitis (A + AD), no cases
of A + AD + multiple food allergies (MFA)). Cluster 2, 'Severe peanut allergy
with frequent allergic multi-morbidity' (62 subjects), had a high proportion of
patients with positive OFC (85%) with the lowest level of peanut protein inducing
a positive OFC (112 mg), 89% allergic subjects, 100% with allergic multi
morbidity (A + AD) and 84% with A + AD + MFA. Cluster 3, 'Mild peanut
allergic/sensitized phenotype' (62 subjects), had the lowest mean age, the lowest
proportion of patients with positive OFC (53%) with a high level of peanut
protein inducing a positive OFC (770 mg), a low percentage of allergic multi
morbidity (48% A + AD + MFA). The two severe peanut-allergic phenotypes were more
frequent in girls. The same clusters were found in the subgroup of patients
without OFC. CONCLUSION & CLINICAL RELEVANCE: Besides the classic markers
associated with lower threshold doses of OFC (such as SPT and rAra h 2), allergic
multi-morbidity and female gender should also be taken into account to better
adapt the progressive dosage of provocation tests.
PMID- 27512925
TI - Gamma-glutamyltransferase-friend or foe within?
AB - Gamma-glutamyltransferase (GGT) is a liver enzyme, which is located on the plasma
membranes of most cells and organ tissues, but more commonly in hepatocytes, and
is routinely used in clinical practice to help indicate liver injury and as a
marker of excessive alcohol consumption. Among the liver enzymes, important
advances have especially been made in understanding the physiological functions
of GGT. The primary role of GGT is the extracellular catabolism of glutathione,
the major thiol antioxidant in mammalian cells, which plays a relevant role in
protecting cells against oxidants produced during normal metabolism; GGT,
therefore, plays an important role in cellular defence. Beyond its physiological
functions, circulating serum GGT has been linked to a remarkable array of chronic
conditions and diseases, which include nonalcoholic fatty liver disease, vascular
and nonvascular diseases and mortality outcomes. This review summarizes the
available epidemiological and genetic evidence for the associations between GGT
and these adverse outcomes, the postulated biologic mechanisms underlying these
associations, outlines areas of outstanding uncertainty and the implications for
clinical practice.
PMID- 27512924
TI - Hemostasis biomarkers and risk of sepsis: the REGARDS cohort.
AB - : Essentials Few studies have investigated the risk of sepsis by baseline
hemostasis biomarkers measures. Baseline hemostasis biomarkers and risk of sepsis
was examined using case-control study design. Increased fibrinogen, factor IX,
and factor XI levels may be associated with risk of sepsis. Hemostasis biomarkers
may provide a target for sepsis mitigation or prevention. SUMMARY: Background
Sepsis is a major public health concern, responsible for more than 750 000
hospitalizations and 200 000 annual deaths in the USA. Few studies have
investigated the association between baseline measurements of hemostasis
biomarkers and the future risk of sepsis. Objective To determine whether
hemostasis biomarkers levels measured at baseline in a cohort of community
dwelling participants are associated with the risk of future sepsis events.
Methods We performed a nested case-control study within the Reasons for
Geographic and Racial Differences in Stroke (REGARDS) cohort. We identified
sepsis hospitalizations occurring over a 10-year period. There were 50 incident
sepsis cases with baseline measurements of hemostasis (fibrinogen, factor VIII,
FIX, FXI, protein C, and D-dimer). Using incidence density sampling, we matched
the 50 sepsis cases with 200 controls by age, sex, and race. We used conditional
logistic regression to evaluate the association between baseline hemostasis
biomarkers and future sepsis events. Results Comparison of 50 sepsis cases with
200 non-sepsis controls showed that sepsis cases had lower education and income,
were more likely to live in the stroke belt, had chronic lung disease, and had
higher albumin level/creatinine level ratios (ACRs). Individuals with higher
baseline fibrinogen levels (adjusted odds ratio [OR] per standard deviation:
1.40, 95% confidence interval [CI] 1.01-1.94), FIX levels ([OR] 1.46, 95% [CI]
1.03-2.07) and FXI levels ([OR]1.52, 95% [CI] 1.04-2.23) were more likely to
experience a sepsis event. Conclusion Baseline fibrinogen, FIX and FXI levels are
associated with future episodes of sepsis. Hemostasis biomarkers may provide
targets for sepsis mitigation or prevention.
PMID- 27512926
TI - Clinical risk factors for delayed bleeding after endoscopic submucosal dissection
for colorectal tumors in Japanese patients.
AB - BACKGROUND: Endoscopic submucosal dissection (ESD) is a curative, standard
therapy for colorectal neoplasms. Some studies have investigated the risk factors
for perforation during colorectal ESD. However, few studies have assessed the
risk factors for delayed bleeding after colorectal ESD. We studied patients
undergoing ESD for colorectal epithelial neoplasms to identify the risk factors
for post-ESD bleeding. PATIENTS AND METHODS: We studied 124 consecutive patients
undergoing ESD for colorectal epithelial neoplasms. To identify risk factors for
delayed bleeding post-ESD, recurrent bleeding post-ESD was compared with patient
related and tumor-related factors. RESULTS: Delayed bleeding after ESD occurred
in 10 (8.1%) lesions of 124 colorectal tumors, and the median time from the end
of ESD to the onset of bleeding was 18.5 h. Delayed bleeding was significantly
higher in tumors located in rectums than in colons (P=0.021), and the number of
occurrences of arterial bleeding during ESD was significantly higher in the
delayed bleeding group than in the nondelayed bleeding group (P=0.002). The
procedure time was significantly longer in the delayed bleeding group than in the
nondelayed bleeding group (P=0.012). On multivariate logistic regression
analysis, tumor location (odds ratio, 10.13; 95% confidence interval, 1.18-87.03;
P=0.035) and three or more occurrences of arterial bleeding during ESD (odds
ratio, 6.86; 95% confidence interval, 1.13-41.5; P=0.036) were significant
independent risk factors for delayed bleeding. CONCLUSION: The presence of
lesions in the rectum and three or more arterial bleeding occurrences during ESD
were risk factors for post-ESD bleeding. Patients with these risk factors should
be followed up carefully after ESD for colorectal epithelial neoplasms.
PMID- 27512927
TI - Randomized-controlled trial of rifaximin versus norfloxacin for secondary
prophylaxis of spontaneous bacterial peritonitis.
AB - BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) is a serious
complication of liver cirrhosis with a high recurrence rate and a marked increase
in mortality. Norfloxacin is used widely for the secondary prophylaxis of SBP;
however, its extensive long-term use has led to an increase in the incidence of
quinolone-resistant and Gram-positive SBP. Rifaximin is a nonabsorbable broad
spectrum antibiotic and does not appear to promote emergence of resistance. The
aim of this study was to compare the safety and efficacy of rifaximin versus
norfloxacin for the secondary prevention of SBP in patients with liver cirrhosis
and ascites. MATERIALS AND METHODS: Two hundred and sixty two cirrhotic patients
with ascites and a previous episode of SBP were assigned randomly to receive
either 1200 mg rifaximin or 400 mg of norfloxacin daily for 6 months. All
patients were monitored clinically each month and with ascitic fluid examination
at the end of 2 and 6 months if not clinically suspected of recurrence earlier.
RESULTS: Recurrence of SBP was significantly lower in the rifaximin group (3.88
vs. 14.13%) compared with the norfloxacin group (P=0.04). The mortality rate was
significantly decreased in the rifaximin group (13.74 vs. 24.43%) compared with
the norfloxacin group (P=0.044). The causes of death between the two groups did
not show a significant difference (P=0.377), but encephalopathy-related deaths
were three folds higher in the norfloxacin group. There was a significant
decrease in the side effects in the rifaximin group versus the norfloxacin group
(P=0.033). CONCLUSION: Rifaximin was more effective than norfloxacin in the
secondary prevention of SBP. Encephalopathy-related mortality and side effects
were fewer in the rifaximin group.
PMID- 27512928
TI - Cascade Biocatalysis for Sustainable Asymmetric Synthesis: From Biobased l
Phenylalanine to High-Value Chiral Chemicals.
AB - Sustainable synthesis of useful and valuable chiral fine chemicals from renewable
feedstocks is highly desirable but remains challenging. Reported herein is a
designed and engineered set of unique non-natural biocatalytic cascades to
achieve the asymmetric synthesis of chiral epoxide, diols, hydroxy acid, and
amino acid in high yield and with excellent ee values from the easily available
biobased l-phenylalanine. Each of the cascades was efficiently performed in one
pot by using the cells of a single recombinant strain over-expressing 4-10
different enzymes. The cascade biocatalysis approach is promising for upgrading
biobased bulk chemicals to high-value chiral chemicals. In addition, combining
the non-natural enzyme cascades with the natural metabolic pathway of the host
strain enabled the fermentative production of the chiral fine chemicals from
glucose.
PMID- 27512929
TI - [Endobronchial Ultrasound Guided Needle Aspiration of a Lung Cyst and
Eosinophilic Pneumonia].
AB - We report the case of a young male patient with a solitary pulmonary echinococcus
cyst. The diagnosis of Cystic Echinococcosis is based on clinical findings,
imaging and serology. In the setting of lung cysts the diagnosis can be
difficult, particularly as the sensitivity of the serologic tests is lower
compared to liver cysts. Bronchoscopic ultrasound of the cystic lesion and
respectively the analysis of the cyst aspirate can lead to the diagnosis. In the
present case an eosinophilic pneumonia as the result of the puncture has to be
discussed.
PMID- 27512930
TI - [Lung Cancer as an Occupational Disease].
AB - Lung cancer is one of the most frequently encountered cancer types. According to
the latest WHO data, about 10 % of this disease are due to occupational exposure
to cancerogens. Asbestos is still the number one carcinogen. Further frequent
causes include quarz and ionizing radiation (uranium mining). Probable causes of
the disease can be identified only with the help of detailed occupational history
taken by a medical specialist and qualified exposure assessment. Without
clarifying the cause of the disease, there is neither a correct insurance
procedure nor compensation for the victim, and furthermore, required preventive
measures cannot be initiated.
PMID- 27512932
TI - [The Swedish Mozart].
PMID- 27512931
TI - [Exon-dependent Subgroup-analysis of the Non-interventional REASON-Study: PFS and
OS in EGFR-mutated NSCLC Patients Treated with Gefitinib or Chemotherapy].
AB - PURPOSE: To analyze the influence of the localization of mutations in the
epidermal growth factor receptor (EGFR) gene on progression-free (PFS) and
overall survival (OS) in patients (pts) with locally advanced or metastatic non
small cell lung cancer (NSCLC) treated with gefitinib (gef) or chemotherapy (CT)
under real world conditions within the REASON study. METHODS: Subgroups of pts
with mutations in exon 19 (n = 141), 18/20 (n = 43), and 21 (n = 104) were
analyzed for PFS and OS according to gef or CT treatment and compared using the
log-rank test. RESULTS: Pts with mutations in exon 19 and 18/20 treated with gef
as first line therapy showed increased PFS and OS compared to CT. This increase
was statistically significant in pts with exon 19 mutation (11.3 vs. 6.5 months),
but was not found in pts with exon 21 mutation (9.1 vs. 9.3 months). Also, OS was
significantly increased in patients with mutation in exon 19 treated with gef
ever over all treatment lines compared to CT (21.8 vs. 10.6 months), whereas this
was not found in pts with mutation in exon 21 (14.1 vs. 13.9 months). CONCLUSION:
Localization and nature of EGFR mutations influences gefitinib treatment outcomes
under routine conditions and should therefore be analyzed in detail.
PMID- 27512933
TI - [Chronic Obstructive Pulmonary Disease (COPD) - Rational Diagnostics and
Therapy].
AB - In general chronic obstructive pulmonary disease (COPD) can be diagnosed in
family practice from history and spirometry. Inconclusive spirometry findings
have to be assessed further by techniques available in a pulmonologist's office.
Further testing is done for differential diagnostic reasons and for prognostic
appraisal. Successful smoking cessation importantly alters the natural downhill
course of the disease. Patient education and rehabilitative interventions (e. g.
participation in lung sport groups) help to improve life quality. Medical
therapies with bronchospasmolytics applied by inhalation as monotherapies, free
and fixed combinations have symptomatic benefit. Considering the increase of
pneumonia risk from inhaled corticosteroids their use should be restricted to
patients with a straightforward indication, e. g. coexisting asthma.
PMID- 27512934
TI - Chemoprevention of basal cell carcinoma: reply from authors.
AB - The review started from the question whether early detection of BCC in the
general (asymptomatic) population could lead to any benefit in terms of outcome
and cost. In other words, should early detection efforts for skin cancer
(secondary prevention) also include BCC? Review of available literature suggests
that early detection and adequate treatment of BCC of the face could increase
cost-effectiveness. Although these results could also pertain to patients who
have had already a history of BCC, their setting is different since they may
already be in a follow-up programme (tertiary prevention). This article is
protected by copyright. All rights reserved.
PMID- 27512935
TI - Spinal Cord Stimulation Modulates Gene Expression in the Spinal Cord of an Animal
Model of Peripheral Nerve Injury.
AB - BACKGROUND AND OBJECTIVES: Previously, we found that application of pulsed
radiofrequency to a peripheral nerve injury induces changes in key genes
regulating nociception concurrent with alleviation of paw sensitivity in an
animal model. In the current study, we evaluated such genes after applying spinal
cord stimulation (SCS) therapy. METHODS: Male Sprague-Dawley rats (n = 6 per
group) were randomized into test and control groups. The spared nerve injury
model was used to simulate a neuropathic pain state. A 4-contact microelectrode
was implanted at the L1 vertebral level and SCS was applied continuously for 72
hours. Mechanical hyperalgesia was tested. Spinal cord tissues were collected and
analyzed using real-time polymerase chain reaction to quantify levels of IL1beta,
GABAbr1, subP, Na/K ATPase, cFos, 5HT3ra, TNFalpha, Gal, VIP, NpY, IL6, GFAP,
ITGAM, and BDNF. RESULTS: Paw withdrawal thresholds significantly decreased in
spared nerve injury animals and stimulation attenuated sensitivity within 24
hours (P = 0.049), remaining significant through 72 hours (P = 0.003). Nerve
injury caused up-regulation of TNFalpha, GFAP, ITGAM, and cFOS as well as down
regulation of Na/K ATPase. Spinal cord stimulation therapy modulated the
expression of 5HT3ra, cFOS, and GABAbr1. Strong inverse relationships in gene
expression relative to the amount of applied current were observed for GABAbr1 (R
= -0.65) and Na/K ATPase (R = -0.58), and a positive linear correlations between
5HT3r (R = 0.80) and VIP (R = 0.50) were observed. CONCLUSIONS: Continuously
applied SCS modulates expression of key genes involved in the regulation of
neuronal membrane potential.
PMID- 27512936
TI - Spinal Cord Stimulation for Treatment of Neuropathic Pain Associated With
Erythromelalgia.
AB - OBJECTIVE: Erythromelalgia is a rare disorder associated with neuropathic pain
that commonly affects the lower extremities. This pain is often refractory to
multimodal treatment. Both pharmacologic management and interventional anesthetic
blocks have been used with varying and often limited success. To date, little
experience has been gained with the use of spinal cord stimulation in treating
pain associated with erythromelalgia. CASE REPORT: We present a case of
successful treatment of pain secondary to erythromelalgia with a spinal cord
stimulator in an 80-year-old woman. This patient had severe pain and debility
secondary to erythromelalgia, having undergone trials of multiple medical
therapies before presenting to our clinic. Dual-lead percutaneous spinal cord
stimulation was successfully implanted without complication, leading to excellent
pain control, now 18 months postimplant. CONCLUSIONS: Spinal cord stimulation may
be a promising treatment of neuropathic pain associated with erythromelalgia.
PMID- 27512938
TI - Editorial.
PMID- 27512937
TI - Subdural Hematoma Associated With Labor Epidural Analgesia: A Case Series.
AB - OBJECTIVE: This report aimed to describe the characteristics and impact of
subdural hematoma (SDH) after labor epidural analgesia. CASE REPORTS: Eleven
obstetric patients had SDHs associated with the use of labor epidural analgesia
over 7 years at a tertiary care hospital. Ten of 11 patients had signs consistent
with postdural puncture headache before the diagnosis of SDH. Five patients (45%)
had a recognized unintentional dural puncture, 1 (9%) had a combined spinal
epidural with a 24-gauge needle, and 5 (45%) had no recognized dural puncture.
For 10 of the 11 cases, SDH was diagnosed at a mean of 4.1 days (range, 1-7 days)
after performance of labor epidural analgesia; one case was diagnosed at 25 days.
Ten (91%) of 11 cases had a second hospital stay for a mean of 2.8 days (range, 2
4 days) for observation, without further requirement for neurosurgical
intervention. One case (9%) had decompressive hemicraniectomy after becoming
unresponsive. The observed rate of labor epidural analgesia-associated SDH was
0.026% (11 in 42,969, approximately 1:3900), and the rate of SDH was 1.1% (5 in
437, approximately 1:87) if a recognized dural puncture occurred during epidural
catheter placement. CONCLUSIONS: Subdural hematoma after labor epidural
anesthesia is rare but potentially more common than historically estimated. Cases
of postdural puncture headache after labor epidural anesthesia should be
monitored closely for severe neurologic signs and symptoms that could herald SDH.
PMID- 27512939
TI - A Wandering Pulmonary Nodule.
PMID- 27512940
TI - Method for Direct Synthesis of alpha-Cyanomethyl-beta-dicarbonyl Compounds with
Acetonitrile and 1,3-Dicarbonyls.
AB - A novel and efficient method for the synthesis of alpha-cyanomethyl-beta
dicarbonyls in moderate to excellent yields is developed by using inactive CH3CN
and simple 1,3-dicarbonyls. A radical mechanism is proposed under the ESI-MS
(electrospray ionization mass spectrometry) analysis results of control
experiments.
PMID- 27512941
TI - Total Synthesis of 11-Saxitoxinethanoic Acid and Evaluation of its Inhibitory
Activity on Voltage-Gated Sodium Channels.
AB - 11-Saxitoxinethanoic acid (SEA) is a member of the saxitoxin (STX) family of
paralytic shellfish poisons, and contains an unusual C-C bond at the C11
position. Reported herein is a total synthesis of SEA. The key to our synthesis
lies in a Mukaiyama aldol condensation reaction of silyl enol ether with
glyoxylate in the presence of an anhydrous fluoride reagent, [Bu4 N][Ph3 SnF2 ],
which directly constructs the crucial C-C bond at the C11 position in SEA. The
NaV Ch-inhibitory activities of SEA and its derivatives were evaluated by means
of cell-based assay. SEA showed an IC50 value of (47+/-12) nm, which is
approximately twice as potent as decarbamoyl-STX (dcSTX).
PMID- 27512942
TI - Enhanced up/down-conversion luminescence and heat: Simultaneously achieving in
one single core-shell structure for multimodal imaging guided therapy.
AB - Upon near-infrared (NIR) light irradiation, the Nd(3+) doping derived down
conversion luminescence (DCL) in NIR region and thermal effect are extremely
fascinating in bio-imaging and photothermal therapy (PTT) fields. However, the
concentration quenching induced opposite changing trend of the two properties
makes it difficult to get desired DCL and thermal effect together in one single
particle. In this study, we firstly designed a unique
NaGdF4:0.3%Nd@NaGdF4@NaGdF4:10%Yb/1%Er@NaGdF4:10%Yb @NaNdF4:10%Yb multiple core
shell structure. Here the inert two layers (NaGdF4 and NaGdF4:10%Yb) can
substantially eliminate the quenching effects, thus achieving markedly enhanced
NIR-to-NIR DCL, NIR-to-Vis up-conversion luminescence (UCL), and thermal effect
under a single 808 nm light excitation simultaneously. The UCL excites the
attached photosensitive drug (Au25 nanoclusters) to generate singlet oxygen
((1)O2) for photodynamic therapy (PDT), while DCL with strong NIR emission serves
as probe for sensitive deep-tissue imaging. The in vitro and in vivo experimental
results demonstrate the excellent cancer inhibition efficacy of this platform due
to a synergistic effect arising from the combined PTT and PDT. Furthermore,
multimodal imaging including fluorescence imaging (FI), photothermal imaging
(PTI), and photoacoustic imaging (PAI) has been obtained, which is used to
monitor the drug delivery process, internal structure of tumor and photo
therapeutic process, thus achieving the target of imaging-guided cancer therapy.
PMID- 27512943
TI - Isoproterenol regulates CD44 expression in gastric cancer cells through
STAT3/MicroRNA373 cascade.
AB - Gastric cancer is a heterogeneous disease, and stem cells are thought to be the
cell of origin contributed to this malignancy. However, studies with breast and
intestinal cancer models show non-stem cancer cells can change their surface
phenotype and convert into tumor-initiating cells induced by the signals
emanating from surrounding tumor microenvironment. Here, we show that CD44 was
expressed at different levels in gastric metastases compared with primary tumors,
and also negatively correlated with the expression of miR-373. By using a panel
of human gastric cancer cell lines and analysis of archived data from The Cancer
Genomics Altas (TCGA) database, we verified the inverse correlation between CD44
and miR-373. Furthermore, the stress-associated hormone, isoproterenol, could
increase the expression levels of "stem"-related proteins, such as CD44, Nanog,
and Rex-1, and induce chemoresistance in gastric cancer cells. Transfection with
miR-373, however, reversed not only the effect of isoproterenol on phenotypic
conversion but also its effect on drug sensitivity. Isoproterenol triggered
downstream target STAT3 mainly through beta2-adrenergic receptors (beta2-ARs).
Activated STAT3 functioned as a miR-373 suppressor by binding to its promoter,
which forms a positive feedback circuit to maintain CD44 activity and direct the
phenotypic conversion from CD44(low) to CD44(hi) expression. Our data suggest an
important role of beta2-AR/STAT3/miR-373 signaling on the transformation of
gastric cancer cells. This study also suggests a potential therapeutic or
preventive treatment for gastric cancer patients who are especially prone to
psychosocial stress.
PMID- 27512944
TI - Precise control of surface electrostatic forces on polymer brush layers with
opposite charges for resistance to protein adsorption.
AB - Various molecular interaction forces are generated during protein adsorption
process on material surfaces. Thus, it is necessary to control them to suppress
protein adsorption and the subsequent cell and tissue responses. A series of
binary copolymer brush layers were prepared via surface-initiated atom transfer
radical polymerization, by mixing the cationic monomer unit and anionic monomer
unit randomly in various ratios. Surface characterization revealed that the
constructed copolymer brush layers exhibited an uniform super-hydrophilic nature
and different surface potentials. The strength of the electrostatic interaction
forces operating on these mixed-charge copolymer brush surfaces was evaluated
quantitatively using force-versus-distance (f-d) curve measurements by atomic
force microscopy (AFM) and probes modified by negatively charged carboxyl groups
or positively charged amino groups. The electrostatic interaction forces were
determined based on the charge ratios of the copolymer brush layers. Notably, the
surface containing equivalent cationic/anionic monomer units hardly interacted
with both the charged groups. Furthermore, the protein adsorption force and the
protein adsorption mass on these surfaces were examined by AFM f-d curve
measurement and surface plasmon resonance measurement, respectively. To clarify
the influence of the electrostatic interaction on the protein adsorption behavior
on the surface, three kinds of proteins having negative, positive, and relatively
neutral net charges under physiological conditions were used in this study. We
quantitatively demonstrated that the amount of adsorbed proteins on the surfaces
would have a strong correlation with the strength of surface-protein interaction
forces, and that the strength of surface-protein interaction forces would be
determined from the combination between the properties of the electrostatic
interaction forces on the surfaces and the charge properties of the proteins.
Especially, the copolymer brush surface composed of equivalent cationic/anionic
monomer units exhibited no significant interaction forces, and dramatically
suppressed the adsorption of proteins regardless of their charge properties. We
conclude that the established methodology could elucidate relationship between
the protein adsorption behavior and molecular interaction, especially the
electrostatic interaction forces, and demonstrated that the suppression of the
electrostatic interactions with the ionic functional groups would be important
for the development of new polymeric biomaterials with a high repellency of
protein adsorption.
PMID- 27512945
TI - Parental infant jaundice colour card design successfully validated by comparing
it with total serum bilirubin.
AB - AIM: We designed a jaundice colour card that could be used by the parents of
neonates and validated it by comparing it with total serum bilirubin levels.
METHODS: There were 106 term Chinese neonates in the study. The majority weighed
between 2500 g and 3499 g (63%) and had a gestational age of 37-40 weeks (77%).
The jaundice colour card and photometric determination were used to screen for
neonatal jaundice and compared with serum bilirubin. RESULTS: The bilirubin
levels were measured by mothers using the jaundice colour card, and 67% of the
measurements were taken at 11-20 days (range 3-30). The measurements at the
infant's forehead, cheek and sternum showed strong correlations with total serum
bilirubin. The mean differences between the total serum bilirubin and the
jaundice colour card measurements from the forehead, cheek and sternum were 1.9
mg/dL, 0.3 mg/dL and 1.5 mg/dL, respectively. When total serum bilirubin >13
mg/dL was used as the cut-off point, the areas under the receiver operating
characteristics curves were 0.934 for the forehead, 0.985 for the cheek and 0.966
for the sternum. CONCLUSION: We established the validity of the jaundice colour
card as a parental measurement tool for jaundice in Chinese neonates, and the
cheek was the best measurement site.
PMID- 27512946
TI - In vivo enzymatic modulation of IgG antibodies prevents immune complex-dependent
skin injury.
AB - IgG antibodies are potent inducers of proinflammatory responses by cross-linking
Fc receptors on innate immune effector cells resulting in tissue injury. The
recently discovered enzymes endoglycosidase S (EndoS) and IgG-degrading enzyme
(IdeS) of Streptococcus pyogenes are able to modulate the interaction between IgG
antibodies and the Fc receptors, by hydrolysis of the glycan associated with the
heavy chain of the IgG molecule (EndoS), or cleavage in the hinge region of the
heavy IgG chain (IdeS). In this work, we investigated their ability to inhibit
damage mediated by skin-bound antibodies in vivo in two different experimental
models, the Arthus reaction, and epidermolysis bullosa acquisita, an autoimmune
blistering skin disease associated with autoantibodies against type VII collagen.
We demonstrate that both enzymes efficiently interfere with IgG-mediated
proinflammatory processes, offering a great asset to specifically target
pathological IgG antibodies in the skin and holding great promise for future
applications in human therapy.
PMID- 27512947
TI - Patient-oncologist alliance and psychosocial well-being in Chinese society
strongly affect cancer management adherence with cancer of unknown primary.
AB - BACKGROUND: Patient-oncologist alliance and psychosocial well-being have strong
associations with adherence to cancer management. For patients with cancer of
unknown primary (CUP), adherence is crucial to treatment or occult primary
screening plans. There has been no study investigating the relationship between
alliance, psychosocial factors, and adherence in such patients or in Chinese
sociocultural settings. METHODS: The measures of alliance, psychosocial well
being, and adherence willingness were administered to patients with CUP, with a
mean age of 58.33 +/- 11.24 years. Multiple linear regression models were applied
to investigate the independent relationship between alliance and adherence by
controlling for socioeconomic and psychosocial confounders. RESULTS: Alliance was
found to be independently and positively associated with greater adherence
willingness and adherence to treatment and follow-up screening after controlling
for significant confounders, including medical conditions, psychosocial well
being variables, and socioeconomic factors. CONCLUSION: Stronger patient
oncologist alliance may foster enhanced adherence to treatment and follow-up
screening in patients with CUP. Patient-oncologist alliance seems affected by
socioeconomic factors and psychosocial well-being in the Chinese sociocultural
settings.
PMID- 27512948
TI - Three-dimensional modelling identifies novel genetic dependencies associated with
breast cancer progression in the isogenic MCF10 model.
AB - The initiation and progression of breast cancer from the transformation of the
normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a
complex process involving the acquisition of genetic alterations and changes in
gene expression, alongside microenvironmental and recognized histological
alterations. Here, we sought to comprehensively characterise the genomic and
transcriptomic features of the MCF10 isogenic model of breast cancer progression,
and to functionally validate potential driver alterations in three-dimensional
(3D) spheroids that may provide insights into breast cancer progression, and
identify targetable alterations in conditions more similar to those encountered
in vivo. We performed whole genome, exome and RNA sequencing of the MCF10
progression series to catalogue the copy number and mutational and transcriptomic
landscapes associated with progression. We identified a number of predicted
driver mutations (including PIK3CA and TP53) that were acquired during
transformation of non-malignant MCF10A cells to their malignant counterparts that
are also present in analysed primary breast cancers from The Cancer Genome Atlas
(TCGA). Acquisition of genomic alterations identified MYC amplification and
previously undescribed RAB3GAP1-HRAS and UBA2-PDCD2L expressed in-frame fusion
genes in malignant cells. Comparison of pathway aberrations associated with
progression showed that, when cells are grown as 3D spheroids, they show
perturbations of cancer-relevant pathways. Functional interrogation of the
dependency on predicted driver events identified alterations in HRAS, PIK3CA and
TP53 that selectively decreased cell growth and were associated with progression
from preinvasive to invasive disease only when cells were grown as spheroids. Our
results have identified changes in the genomic repertoire in cell lines
representative of the stages of breast cancer progression, and demonstrate that
genetic dependencies can be uncovered when cells are grown in conditions more
like those in vivo. The MCF10 progression series therefore represents a good
model with which to dissect potential biomarkers and to evaluate therapeutic
targets involved in the progression of breast cancer. (c) 2016 The Authors. The
Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological
Society of Great Britain and Ireland.
PMID- 27512949
TI - Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate
osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis
patients.
AB - Periodontitis impairs the osteogenic differentiation of human periodontal
mesenchymal stem cells (hPDLSCs), but the underlying molecular mechanisms are
still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to
have significant roles under both physiologic and pathological conditions. In
this study, we performed comprehensive lncRNA profiling by lncRNA microarray
analysis and identified a novel lncRNA, osteogenesis impairment-related lncRNA of
PDLSCs from periodontitis patients (lncRNA-POIR), the expression of which was
significantly decreased in PDLSCs from periodontitis patients (pPDLSCs) and was
upregulated by osteogenic induction. To study the functions of lncRNA-POIR, we
prepared cells with overexpression and knockdown of lncRNA-POIR and found that
lncRNA-POIR positively regulated osteogenic differentiation of hPDLSCs and
pPDLSCs both in vitro and in vivo. Using quantitative real-time PCRs (qPCRs) and
luciferase reporter assays, we demonstrated that lncRNA-POIR may act as a
competing endogenous RNA (ceRNA) for miR-182, leading to derepression of its
target gene, FoxO1. In this process, lncRNA-POIR and miR-182 suppress each other
and form a network to regulate FoxO1. FoxO1 increased bone formation of pPDLSCs
by competing with TCF-4 for beta-catenin and inhibiting the canonical Wnt
pathway. Finally, inflammation increases miR-182 expression through the nuclear
factor-kappaB pathway, and the miR-182 overexpression in the inflammatory
microenvironment resulted in an imbalance in the lncRNA-POIR-miR-182 regulatory
network. In conclusion, our results provide novel evidence that this lncRNA-miRNA
(microRNA) regulatory network has a significant role in osteogenic
differentiation of pPDLSCs and that it has potential as a therapeutic target in
mesenchymal stem cells during inflammation.
PMID- 27512950
TI - Glucolipotoxicity initiates pancreatic beta-cell death through TNFR5/CD40
mediated STAT1 and NF-kappaB activation.
AB - Type 2 diabetes is a chronic metabolic disorder, where failure to maintain normal
glucose homoeostasis is associated with, and exacerbated by, obesity and the
concomitant-elevated free fatty acid concentrations typically found in these
patients. Hyperglycaemia and hyperlipidaemia together contribute to a decline in
insulin-producing beta-cell mass through activation of the transcription factors
nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and
signal transducer and activator of transcription (STAT)-1. There are however a
large number of molecules potentially able to modulate NF-kappaB and STAT1
activity, and the mechanism(s) by which glucolipotoxicity initially induces NF
kappaB and STAT1 activation is currently poorly defined. Using high-density
microarray analysis of the beta-cell transcritptome, we have identified those
genes and proteins most sensitive to glucose and fatty acid environment. Our data
show that of those potentially able to activate STAT1 or NF-kappaB pathways,
tumour necrosis factor receptor (TNFR)-5 is the most highly upregulated by
glucolipotoxicity. Importantly, our data also show that the physiological ligand
for TNFR5, CD40L, elicits NF-kappaB activity in beta-cells, whereas selective
knockdown of TNFR5 ameliorates glucolipotoxic induction of STAT1 expression and
NF-kappaB activity. This data indicate for the first time that TNFR5 signalling
has a major role in triggering glucolipotoxic islet cell death.
PMID- 27512951
TI - Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy.
AB - Autophagy is an evolutionarily conserved catabolic process by which cells degrade
intracellular proteins and organelles in the lysosomes. Canonical autophagy
requires all autophagy proteins (ATGs), whereas noncanonical autophagy is
activated by diverse agents in which some of the essential autophagy proteins are
dispensable. How noncanonical autophagy is induced and/or inhibited is still
largely unclear. In this study, we demonstrated that AMDE-1, a recently
identified chemical that can induce canonical autophagy, was able to elicit
noncanonical autophagy that is independent of the ULK1 (unc-51-like kinase 1)
complex and the Beclin1 complex. AMDE-1-induced noncanonical autophagy could be
specifically suppressed by various V-ATPase (vacuolar-type H(+)-ATPase)
inhibitors, but not by disturbance of the lysosome function or the intracellular
ion redistribution. Similar findings were applicable to a diverse group of
stimuli that can induce noncanonical autophagy in a FIP200-independent manner.
AMDE-1-induced LC3 lipidation was colocalized with the Golgi complex, and was
inhibited by the disturbance of Golgi complex. The integrity of the Golgi complex
was also required for multiple other agents to stimulate noncanonical LC3
lipidation. These results suggest that the Golgi complex may serve as a membrane
platform for noncanonical autophagy where V-ATPase is a key player. V-ATPase
inhibitors could be useful tools for studying noncanonical autophagy.
PMID- 27512952
TI - Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.
AB - Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the
deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive
neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko
mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko
NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal
degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are
selectively able to drive neuronal degeneration when cocultured with healthy
neurons. This phenotype suggests concurrent oxidative damage with metabolic
dysfunction. Similar patterns were observed in murine IDS-ko animals and in human
MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was
reversed by low oxygen conditions and treatment with vitamin E, which also
reversed the toxic effect on cocultured neurons. Moreover, at very early stages
of disease we detected in vivo the development of a neuroinflammatory background
that precedes astroglial degeneration, thus suggesting a novel model of MPSII
pathogenesis, with neuroinflammation preceding glial degeneration, which is
finally followed by neuronal death. This hypothesis is also consistent with the
progression of white matter abnormalities in MPSII patients. Our study represents
a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests
the antioxidant molecules as potential therapeutic tools to delay MPSII onset and
progression.
PMID- 27512953
TI - Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes
neutrophil extracellular traps.
AB - Neutrophil extracellular trap (NET) ejected from activated dying neutrophils is a
highly ordered structure of DNA and selected proteins capable to eliminate
pathogenic microorganisms. Biochemical determinants of the non-randomly formed
stable NETs have not been revealed so far. Studying the formation of human NETs
we have observed that polyamines were incorporated into the NET. Inhibition of
myeloperoxidase, which is essential for NET formation and can generate reactive
chlorinated polyamines through hypochlorous acid, decreased polyamine
incorporation. Addition of exogenous primary amines that similarly to polyamines
inhibit reactions catalyzed by the protein cross-linker transglutaminases
(TGases) has similar effect. Proteomic analysis of the highly reproducible
pattern of NET components revealed cross-linking of NET proteins through
chlorinated polyamines and E(gamma-glutamyl)lysine as well as bis-gamma-glutamyl
polyamine bonds catalyzed by the TGases detected in neutrophils. Competitive
inhibition of protein cross-linking by monoamines disturbed the cross-linking
pattern of NET proteins, which resulted in the loss of the ordered structure of
the NET and significantly reduced capacity to trap bacteria. Our findings provide
explanation of how NETs are formed in a reproducible and ordered manner to
efficiently neutralize microorganisms at the first defense line of the innate
immune system.
PMID- 27512955
TI - Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced
apoptosis via autophagy-dependent and -independent DR5 upregulation.
AB - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potent
cancer cell-specific apoptosis-inducing cytokine with little toxicity to most
normal cells. However, acquired resistance of cancer cells to TRAIL is a
roadblock. Agents that can either potentiate the effect of TRAIL or overcome
resistance to TRAIL are urgently needed. This article reports that ginsenoside
compound K (CK) potentiates TRAIL-induced apoptosis in HCT116 colon cancer cells
and sensitizes TRAIL-resistant colon cancer HT-29 cells to TRAIL. On a cellular
mechanistic level, CK downregulated cell survival proteins including Mcl-1, Bcl
2, surviving, X-linked inhibitor of apoptosis protein and Fas-associated death
domain-like IL-1-converting enzyme-inhibitory protein, upregulated cell pro
apoptotic proteins including Bax, tBid and cytochrome c, and induced the cell
surface expression of TRAIL death receptor DR5. Reduction of DR5 levels by siRNAs
significantly decreases CK- and TRAIL-mediated apoptosis. Importantly, our
results indicate, for the first time, that DR5 upregulation is mediated by
autophagy, as blockade of CK-induced autophagy by 3-MA, LY294002 or Atg7 siRNAs
substantially decreases DR5 upregulation and reduces the synergistic effect.
Furthermore, CK-stimulated autophagy is mediated by the reactive oxygen species-c
Jun NH2-terminal kinase pathway. Moreover, we found that p53 and the C/EBP
homologous (CHOP) protein is also required for DR5 upregulation but not related
with autophagy. Our findings contribute significantly to the understanding of the
mechanism accounted for the synergistic anticancer activity of CK and TRAIL, and
showed a novel mechanism related with DR5 upregulation.
PMID- 27512956
TI - KDM5A controls bone morphogenic protein 2-induced osteogenic differentiation of
bone mesenchymal stem cells during osteoporosis.
AB - Bone morphogenetic protein 2 (BMP2) has been used to induce bone regeneration by
promoting osteogenic differentiation of bone marrow-derived mesenchymal stem
cells (MSCs). However, its effect is attenuated in osteoporotic conditions by
unknown mechanisms. In this study, we investigated the molecular mechanisms of
reduced osteogenic effect of BMP2 in osteoporotic conditions. By interrogating
the microarray data from osteoporosis patients, we revealed an upregulation of
the epigenetic modifying protein lysine (K)-specific demethylase 5A (KDM5A) and
decreased Runt-related transcription factor 2 (RUNX2) expression. Further studies
were focused on the role of KDM5A in osteoporosis. We first established
ovariectomized (OVX) mouse model and found that the BMP2-induced osteogenic
differentiation of osteoporotic MSCs was impaired. The elevated level of KDM5A
was confirmed in osteoporotic MSCs. Overexpression of KDM5A in normal MSCs
inhibited BMP2-induced osteogenesis. Moreover, osteogenic differentiation of
osteoporotic MSCs was restored by specific KDM5A short hairpin RNA or inhibitor.
Furthermore, by chromatin immunoprecipitation assay we demonstrated that KDM5A
functions as endogenous modulator of osteogenic differentiation by decreasing
H3K4me3 levels on promoters of Runx2, depend on its histone methylation activity.
More importantly, we found an inhibitory role of KDM5A in regulating bone
formation in osteoporotic mice, and pretreatment with KDM5A inhibitor partly
rescued the bone loss during osteoporosis. Our results show, for the first time,
that KDM5A-mediated H3K4me3 modification participated in the etiology of
osteoporosis and may provide new strategies to improve the clinical efficacy of
BMP2 in osteoporotic conditions.
PMID- 27512954
TI - Regulatory non-coding RNA: new instruments in the orchestration of cell death.
AB - Non-coding RNA (ncRNA) comprises a substantial portion of primary transcripts
that are generated by genomic transcription, but are not translated into protein.
The possible functions of these once considered 'junk' molecules have incited
considerable interest and new insights have emerged. The two major members of
ncRNAs, namely micro RNA (miRNA) and long non-coding RNA (lncRNA), have important
regulatory roles in gene expression and many important physiological processes,
which has recently been extended to programmed cell death. The previous paradigm
of programmed cell death only by apoptosis has recently expanded to include
modalities of regulated necrosis (RN), and particularly necroptosis. However,
most research efforts in this field have been on protein regulators, leaving the
role of ncRNAs largely unexplored. In this review, we discuss important findings
concerning miRNAs and lncRNAs that modulate apoptosis and RN pathways, as well as
the miRNA-lncRNA interactions that affect cell death regulation.
PMID- 27512957
TI - Oncogenic microtubule hyperacetylation through BEX4-mediated sirtuin 2
inhibition.
AB - Five brain-expressed X-linked (BEX) gene members (BEX1-5) are arranged in tandem
on chromosome X, and are highly conserved across diverse species. However, little
is known about the function and role of BEX. This study represents a first
attempt to demonstrate the molecular details of a novel oncogene BEX4. Among BEX
proteins, BEX4 localizes to microtubules and spindle poles, and interacts with
alpha-tubulin (alpha-TUB) and sirtuin 2 (SIRT2). The overexpression of BEX4 leads
to the hyperacetylation of alpha-TUB by inhibiting SIRT2-mediated deacetylation.
Furthermore, we found BEX4 expression conferred resistance to apoptotic cell
death but led to acquisition of aneuploidy, and also increased the proliferating
potential and growth of tumors. These results suggest that BEX4 overexpression
causes an imbalance between TUB acetylation and deacetylation by SIRT2 inhibition
and induces oncogenic aneuploidy transformation.
PMID- 27512958
TI - Cell surface galectin-3 defines a subset of chemoresistant gastrointestinal tumor
initiating cancer cells with heightened stem cell characteristics.
AB - Recurrence of gastrointestinal adenocarcinomas after surgery and chemotherapy may
be attributed, in part, to the presence of a small population of tumor-initiating
cancer stem cells (CSC). The expression of galectin-3 (Gal3), a multifunctional
oncolectin, has been associated with biological behaviors associated with CSC. We
examined the ability of Gal3 to characterize the CSC phenotype, and to identify a
clinically important gastrointestinal cancer CSC population. Human colorectal and
pancreatic cancer cell lines were sorted to identify subpopulations expressing
commonly used CSC markers, and Gal3-positive CSC subpopulations. The association
of Gal3 with the stem cell properties and alterations of these phenotypes by
manipulation of Gal3 expression was examined. Gastrointestinal cancer cell lines
contain both Gal3-positive and Gal3-negative subpopulations. Gal3-positive CSCs
are characterized by high ALDH activity, enhanced self-renewal ability in vitro
(sphere formation) and tumor forming ability in vivo, and resistance to
chemotherapeutic agents and death-receptor-mediated apoptosis compared to Gal3
negative CSCs. Silencing Gal3 modifies this behavior. Cell surface Gal3
expression identifies a subset of CSCs in gastrointestinal cancers with high
levels of stem cell characteristics, including chemoresistance. This may provide
a platform for developing treatment strategies that target CSC.
PMID- 27512960
TI - Landscape spatial configuration is a key driver of wild bee demographics.
AB - The majority of studies investigating the effects of landscape composition and
configuration on bee populations have been conducted in regions of intensive
agricultural production, ignoring regions which are dominated by seminatural
habitats, such as the islands of the Aegean Archipelago. In addition, research so
far has focused on the landscape impacts on bees sampled in cropped fields while
the landscape effects on bees inhabiting seminatural habitats are understudied.
Here, we investigate the impact of the landscape on wild bee assemblages in 66
phryganic (low scrubland) communities on 8 Aegean islands. We computed landscape
metrics (total area and total perimeter-area ratio) in 4 concentric circles (250,
500, 750, and 1000 m) around the center of each bee sampling site including 3
habitat groups (namely phrygana, cultivated land, and natural forests). We
further measured the local flower cover in 25 quadrats distributed randomly at
the center of each sampling site. We found that the landscape scale is more
important than the local scale in shaping abundance and species richness of bees.
Furthermore, habitat configuration was more important than the total area of
habitats, probably because it affects bees' movement across the landscape.
Phrygana and natural forests had a positive effect on bee demographics, while
cultivated land had a negative effect. This demonstrates that phryganic
specialists drive bee assemblages in these seminatural landscapes. This finding,
together with the shown importance of landscape scale, should be considered for
the management of wild bees with special emphasis placed on the spatial
configuration of seminatural habitats.
PMID- 27512959
TI - Antitherapeutic antibody-mediated hepatotoxicity of recombinant human Apo2L/TRAIL
in the cynomolgus monkey.
AB - Apo2L/TRAIL is a member of the tumor necrosis factor superfamily and an important
inducer of apoptosis. Recombinant human (rhu) Apo2L/TRAIL has been attractive as
a potential cancer therapeutic because many types of tumor cells are sensitive to
its apoptosis-inducing effects. Nonclinical toxicology studies were conducted to
evaluate the safety of rhuApo2L/TRAIL for possible use in humans. The cynomolgus
monkey was chosen for this safety assessment based on high protein sequence
homology between human and cynomolgus Apo2L/TRAIL and comparable expression of
their receptors. Although hepatotoxicity was observed in repeat-dose monkey
studies with rhuApo2L/TRAIL, all animals that displayed hepatotoxicity had
developed antitherapeutic antibodies (ATAs). The cynomolgus ATAs augmented the
cytotoxicity of rhuApo2L/TRAIL but not of its cynomolgus counterpart. Of note,
human and cynomolgus Apo2L/TRAIL differ by four amino acids, three of which are
surface-exposed. In vivo studies comparing human and cynomolgus Apo2L/TRAIL
supported the conclusion that these distinct amino acids served as epitopes for
cross-species ATAs, capable of crosslinking rhuApo2L/TRAIL and thus triggering
hepatocyte apoptosis. We describe a hapten-independent mechanism of immune
mediated, drug-related hepatotoxicity - in this case - associated with the
administration of a human recombinant protein in monkeys. The elucidation of this
mechanism enabled successful transition of rhuApo2L/TRAIL into human clinical
trials.
PMID- 27512961
TI - Gap junction proteins and the wiring (Rewiring) of neuronal circuits.
AB - The unique morphology and pattern of synaptic connections made by a neuron during
development arise in part by an extended period of growth in which cell-cell
interactions help to sculpt the arbor into its final shape, size, and
participation in different synaptic networks. Recent experiments highlight a
guiding role played by gap junction proteins in controlling this process. Ectopic
and overexpression studies in invertebrates have revealed that the selective
expression of distinct gap junction genes in neurons and glial cells is
sufficient to establish selective new connections in the central nervous systems
of the leech (Firme et al. [2012]: J Neurosci 32:14265-14270), the nematode
(Rabinowitch et al. [2014]: Nat Commun 5:4442), and the fruit fly (Pezier et al.,
2016: PLoS One 11:e0152211). We present here an overview of this work and suggest
that gap junction proteins, in addition to their synaptic/communicative
functions, have an instructive role as recognition and adhesion factors. (c) 2016
Wiley Periodicals, Inc. Develop Neurobiol 77: 575-586, 2017.
PMID- 27512963
TI - Lifetime risk of stroke in young-aged and middle-aged Chinese population: the
Chinese Multi-Provincial Cohort Study.
AB - OBJECTIVE: Stroke is a major cause of premature death in China. Early prevention
of stroke requires a more effective method to differentiate the stroke risk among
young-aged and middle-aged individuals than the 10-year risk of cardiovascular
disease. This study aimed to establish a lifetime stroke risk model and risk
charts for the young-aged and middle-aged population in China. METHODS: The
Chinese Multi-Provincial Cohort Study participants (n = 21 953) aged 35-84 years
without cardiovascular disease at baseline were followed for 18 years (263 016
person-years). Modified Kaplan-Meier method was used to estimate the mean
lifetime stroke risk up to age of 80 years and the lifetime stroke risk according
to major stroke risk factors for the population aged 35-60 years. RESULTS: A
total of 917 participants developed first-ever strokes. For the participants aged
35-40 years (98 stroke cases), the lifetime stroke risk was 18.0 and 14.7% in men
and women, respectively. Blood pressure most effectively discriminated the
lifetime stroke risk. The lifetime risk of stroke for the individuals with all
risk factors optimal was 8-10 times lower compared with those with two or more
high risk factors at age 35-60 years at baseline. CONCLUSION: In young-aged and
middle-aged population, the lifetime stroke risk will keep very low if major risk
factors especially blood pressure level is at optimal levels, but the risk
substantially increases even with a slight elevation of major risk factors, which
could not be identified using 10-year risk estimation.
PMID- 27512964
TI - Hypertension types defined by clinic and ambulatory blood pressure in 14 143
patients referred to hypertension clinics worldwide. Data from the ARTEMIS study.
AB - OBJECTIVE: The Ambulatory blood pressure Registry TEleMonitoring of hypertension
and cardiovascular rISk project was designed to set up an international registry
including clinic blood pressure (CBP) and ambulatory blood pressure (ABP)
measurements in patients attending hypertension clinics in all five continents,
aiming to assess different daily life hypertension types. METHODS: Cross
sectional ABP, CBP and demographic data, medical history and cardiovascular risk
profile were provided from existing databases by hypertension clinics.
Hypertension types were evaluated considering CBP (>=140/90 mmHg) and 24-h ABP
(>=130/80 mmHg). RESULTS: Overall, 14 143 patients from 27 countries across all
five continents were analyzed (Europe 73%, Africa 3%, America 9%, Asia 14% and
Australia 2%). Mean age was 57 +/- 14 years, men 51%, treated for hypertension
46%, cardiovascular disease 14%, people with diabetes 14%, dyslipidemia 33% and
smokers 19%. The prevalence of hypertension was higher by CBP than by ABP
monitoring (72 vs. 60%, P < 0.0001). Sustained hypertension (elevated CBP and
ABP) was detected in 49% of patients. White-coat hypertension (WCH, elevated CBP
with normal ABP) was more common than masked hypertension (elevated ABP with
normal CBP) (23 vs. 10%; P < 0.0001). Sustained hypertension was more common in
Europe and America and in elderly, men, obese patients with cardiovascular
comorbidities. WCH was less common in Australia, America and Africa, and more
common in elderly, obese women. Masked hypertension was more common in Asia and
in men with diabetes. Smoking was a determinant for sustained hypertension and
masked hypertension. CONCLUSION: Our analysis showed an unbalanced distribution
of WCH and masked hypertension patterns among different continents, suggesting an
interplay of genetic and environmental factors, and likely also different
healthcare administrative and practice patterns.
PMID- 27512965
TI - Vegetarian diet reduces the risk of hypertension independent of abdominal obesity
and inflammation: a prospective study.
AB - OBJECTIVES: A vegetarian diet may prevent elevation of blood pressures and lower
the risk for hypertension through lower degrees of obesity, inflammation, and
insulin resistance. This study investigated the association between a vegetarian
diet and hypertension incidence in a cohort of Taiwanese adult nonsmokers and
examined whether this association was mediated through inflammation, abdominal
obesity, or insulin resistance (using fasting glucose as a proxy). METHODS: This
matched cohort study was from the 1994-2008 MJ Health Screening Database. Each
vegetarian was matched with five nonvegetarians by age, sex, and study site. The
analysis included 4109 nonsmokers (3423 nonvegetarians and 686 vegetarians),
followed for a median of 1.61 years. The outcome includes hypertension incidence,
as well as SBP and DBP levels. Regression analysis was performed to assess the
association between vegetarian diet and hypertension incidence or future blood
pressure levels in the presence/absence of potential mediators. RESULTS:
Vegetarians had a 34% lower risk for hypertension, adjusting for age and sex
(odds ratio: 0.66, 95% confidence interval: 0.50-0.87; SBP: -3.3 mmHg, P < 0.001;
DBP: -1.5 mmHg, P < 0.001). The results stay statistically significant after
further adjustment for C-reactive protein, waist circumference, and fasting
glucose (odds ratio: 0.72, 95% confidence interval: 0.55-0.86; SBP: -2.4 mmHg, P
< 0.05; DBP: -1.1 mmHg, P < 0.05). The protective association between vegetarian
diet and hypertension appeared to be consistent across age groups. CONCLUSION:
Taiwanese vegetarians had lower incidence of hypertension than nonvegetarians.
Vegetarian diets may protect against hypertension beyond lower abdominal obesity,
inflammation, and insulin resistance.
PMID- 27512966
TI - Preconception blood pressure and risk of preterm birth: a large cohort study in
China.
AB - BACKGROUND: To examine whether blood pressure (BP) in the preconceptional period
was associated with preterm birth in Chinese women. METHODS: The data are from a
large population-based cohort study established to evaluate the effectiveness of
the campaign to prevent neural tube defects in 21 Chinese counties. We included
44 494 singleton live births delivered at gestational ages of 20-42 weeks to
women who were registered before pregnancy in seven counties in southern China.
Blood pressure was measured during registration by trained healthcare workers. We
used logistic regression to evaluate the associations between prepregnancy blood
pressure and increased risk of preterm birth, adjusting for potential
confounders. RESULTS: The study size had 93% power (alpha=0.05) to detect an
increase of 38% over the unexposed rate of 5.32% for preterm birth. The
prevalence of hypertension of study population in prepregnancy was 4.55% (2023/44
494). The incidence of preterm birth was 5.73% for hypertension group and 5.32%
for nonhypertension group. Compared with nonhypertension group, hypertension
group did not show significant increased risk for preterm birth overall [adjusted
risk ratio (RR)=1.10, 95% confidence interval (CI) 0.91-1.34], iatrogenic subtype
[adjusted RR=1.21, 95% CI 0.78-1.88], or noniatrogenic subtype [adjusted RR=1.08,
95% CI 0.88-1.34]. When the participants with normal blood pressure were used as
the reference, the adjusted RRs of noniatrogenic preterm birth were 0.79 (0.70
0.89) for prehypertensive women. CONCLUSION: Our results do not support the
association between hypertension or higher blood pressure prior to pregnancy and
the increased risk of preterm birth.
PMID- 27512962
TI - Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis.
AB - Neurotransmitters, including catecholamines and serotonin, play a crucial role in
maintaining homeostasis in the human body. Studies on these neurotransmitters
mainly revolved around their role in the "fight or flight" response, transmitting
signals across a chemical synapse and modulating blood flow throughout the body.
However, recent research has demonstrated that neurotransmitters can play a
significant role in the gastrointestinal (GI) physiology. Norepinephrine (NE),
epinephrine (E), dopamine (DA), and serotonin have recently been a topic of
interest because of their roles in the gut physiology and their potential roles
in GI and central nervous system pathophysiology. These neurotransmitters are
able to regulate and control not only blood flow, but also affect gut motility,
nutrient absorption, GI innate immune system, and the microbiome. Furthermore, in
pathological states, such as inflammatory bowel disease (IBD) and Parkinson's
disease, the levels of these neurotransmitters are dysregulated, therefore
causing a variety of GI symptoms. Research in this field has shown that exogenous
manipulation of catecholamine serum concentrations can help in decreasing
symptomology and/or disease progression. In this review article, we discuss the
current state-of-the-art research and literature regarding the role of
neurotransmitters in regulation of normal GI physiology, their impact on several
disease processes, and novel work focused on the use of exogenous hormones and/or
psychotropic medications to improve disease symptomology. J. Cell. Physiol. 232:
2359-2372, 2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27512967
TI - Effect of renal sympathetic denervation on hepatic glucose metabolism and blood
pressure in a rat model of insulin resistance.
AB - OBJECTIVE: Hypertension and diabetes are associated with impaired glucose
metabolism and insulin resistance. Chronic activation of the sympathetic nervous
system may contribute to either condition. The purpose of this study was to
investigate the effect of renal denervation on glucose kinetics and insulin
signal pathways in high-fat diet (HFD)-fed rats. METHODS: We examined the effects
of renal denervation on glucose kinetics and insulin sensitivity in HFD-fed rats
with a hyperinsulinemic-euglycemic clamp technique combined with [3-H] glucose
and [U-C]-lactate as a tracer. We also analyzed in vivo the flux through glucose
6-phosphatase and the relative contribution of gluconeogenesis and glycogenolysis
in renal denervation rats. In addition, western blotting was used to identify the
activities of insulin signaling proteins. RESULTS: Renal denervation in HFD-fed
rats markedly decreased blood pressure and hepatic glucose production. Hepatic
glucose production reduction in renal-denervation-treated rats includes decrease
in glycogenolysis by 18.2% for left renal denervation or 31.9% for bilateral
renal denervation and decrease in gluconeogenesis by 16.3% for left renal
denervation or 42.8% for bilateral renal denervation. These changes were
accompanied by decreased hepatic expression of glucose-6-phosphatase and
phosphoenolpyruvate carboxykinase. Importantly, renal denervation increased
phosphorylation of insulin receptors, insulin receptor substrate-1 and Akt kinase
in HFD-fed rats. CONCLUSION: These data corroborate the notion that renal
denervation potentiates hepatic insulin sensitivity.
PMID- 27512968
TI - Threshold for diagnosing hypertension by automated office blood pressure using
random sample population data.
AB - OBJECTIVE: Manual office blood pressure (BP) is still recommended for diagnosing
hypertension. However, its predictive value is decreased by errors in measurement
technique and the white-coat effect. The errors can be eliminated by automated
office BP (AOBP) measurement taking multiple readings with the participant
resting quietly alone. Therefore, use of AOBP in clinical practice requires a
threshold value for hypertension diagnosis. The aim of the present study was to
determine an AOBP threshold corresponding to the 140/90 mmHg manual office BP
using data from a large random population sample. METHODS: In 2145 participants
(mean age 47.3 +/- 11.3 years) randomly selected from a Brno population aged 25
64 years, BP was measured using manual mercury and automated office
sphygmomanometers. RESULTS: Manual SBP (mean difference 6.39 +/- 9.76 mmHg) and
DBP (mean difference 2.50 +/- 6.54 mmHg) were higher than the automated BP.
According to polynomial regression, automated systole of 131.06 (95% confidence
interval 130.43-131.70) and diastole of 85.43 (95% confidence interval 85.03
85.82) corresponded to the manual BP of 140/90 mmHg. Using this cut-off, the
white-coat hypertension was present in 24% of participants with elevated manual
BP, whereas 10% had masked hypertension and 11% masked uncontrolled hypertension.
In individuals with masked uncontrolled hypertension, only AOBP was associated
with the urinary albumin-creatinine ratio, whereas there was no association with
manual BP. CONCLUSION: AOBP of 131/85 mmHg corresponds to the manual BP of 140/90
mmHg. This value may be used as a threshold for diagnosing hypertension using
AOBP. However, outcome-driven studies are required to confirm this threshold.
PMID- 27512969
TI - Histone deacetylase and GATA-binding factor 6 regulate arterial remodeling in
angiotensin II-induced hypertension.
AB - OBJECTIVE: Histone deacetylase (HDAC) inhibitors have been reported to improve
essential and secondary hypertension. However, the specific HDAC that might serve
as a therapeutic target and the associated upstream and downstream molecules
involved in regulating hypertension remain unknown. Our study was aimed at
investigating whether a selective inhibitor of class II HDAC (MC1568) modulates
hypertension, elucidating the underlying mechanism. METHODS: Hypertension was
established by administering angiotensin II (Ang II) to mice before treatment
with MC1568. SBP was measured. RESULTS: Treatment with MC1568 reduced elevated
SBP; attenuated arterial remodeling in the kidney's small arteries and thoracic
aorta; and inhibited cell cycle regulatory gene expression, vascular smooth
muscle cell (VSMC) proliferation, DNA synthesis, and VSMC hypertrophy in vivo and
in vitro. Ang II enhanced the expression of phosphorylated HDAC4 and GATA-binding
factor 6 (GATA6) proteins, which were specifically localized in the cytoplasm of
cells in the arteries of kidneys and in aortas. Forced expression and knockdown
of HDAC4 increased and decreased, respectively, the proliferation and expression
of cell cycle genes in VSMCs. GATA6, a newly described binding partner of HDAC4,
markedly enhanced the size and number of VSMCs. Calcium/calmodulin-dependent
kinase IIalpha (CaMKIIalpha), but not HDAC4, translocated from the nucleus to the
cytoplasm in response to Ang II. CaMKIIalpha and protein kinase D1 were
associated with VSMC hypertrophy and hyperplasia via direct interaction with
HDAC4. MC1568 treatment weakened the association between HDAC4 and CaMKIIalpha.
CONCLUSION: These results suggest that class II HDAC inhibition attenuates
hypertension by negatively regulating VSMC hypertrophy and hyperplasia via the
CaMKIIalpha/protein kinase D1/HDAC4/GATA6 pathway.
PMID- 27512970
TI - The association between blood pressure and lipid levels in Europe: European Study
on Cardiovascular Risk Prevention and Management in Usual Daily Practice.
AB - OBJECTIVES: Several studies have suggested a positive association between serum
lipid levels and blood pressure (BP). This study investigated this association in
a large population from 12 European countries. METHODS: Data were taken from the
European Study on Cardiovascular Risk Prevention and Management in Usual Daily
Practice (ClinicalTrials.gov identifier: NCT00882336). Associations between BP
and lipid levels in patients free from cardiovascular disease and with at least
one major cardiovascular disease risk factor (N = 7641) were assessed using
linear regression analyses. RESULTS: Overall, 72.8 and 64.8% of patients had
hypertension and dyslipidaemia, respectively; 47.0% had both conditions.
Regression coefficients (95% confidence interval) for the associations of LDL
cholesterol, non-HDL cholesterol, total cholesterol and apolipoprotein B levels
with SBP, adjusted for age, sex and BMI, were 0.93 mmHg/mmol per l (0.54-1.31),
1.07 mmHg/mmol per l (0.73-1.40), 1.02 mmHg/mmol per l (0.69-1.35) and 4.94
mmHg/g per l (3.43-6.46), respectively. The corresponding values (95% confidence
interval) for the associations with DBP were 0.96 mmHg/mmol per l (0.73-1.19),
0.95 mmHg/mmol per l (0.75-1.15), 0.87 mmHg/mmol per l (0.67-1.07) and 4.33
mmHg/g per l (3.42-5.23), respectively. Most of these associations remained
significant whether patients were treated with statins or not. CONCLUSION: Small
but statistically significant associations between lipid levels and BP were
observed in a large, multinational European population. Further research is
warranted to assess the causality of this association and its implications on the
management of patients with both hypertension and dyslipidaemia.
PMID- 27512971
TI - A systematic review and meta-analysis of randomized controlled trials
investigating the effects of supplementation with Nigella sativa (black seed) on
blood pressure.
AB - Several reports suggest a beneficial effect of Nigella sativa on cardiometabolic
risk factors, including blood pressure (BP). However, the magnitude of the BP
lowering effect of N. sativa remains controversial. We aimed to calculate this
effect size of N. sativa through a systematic review and meta-analysis of
randomized controlled trials (RCTs). PubMed, Cochrane Collaboration Library, and
SCOPUS were used as data sources of RCTs published before 30 August 2015 (in
English only) comparing N. sativa treatment with placebo or standard treatment.
We used random effect models to estimate the difference in BP reductions, I index
and chi statistics to measure and test the interstudy heterogeneity. Random
effect metaregression models were applied to explore the associations between BP
reduction and duration of treatment, dosage of N. sativa, and type of black seed
as potential confounders. Publication bias was evaluated using funnel plot and
Egger's regression asymmetry test. Total 11 RCTs, including 860 hypertensive or
normotensive individuals were eligible, of which 10 compared N. sativa versus
placebo and one versus standard treatment. SBP and DBP means decreased from
132.85 to 125.19 mmHg and from 82.63 to 77.74 mmHg after mean treatment duration
of 8.3 weeks in N. sativa groups, respectively. The difference in reductions as
compared with control/standard groups were -3.26 (-5.10, -1.42; I = 59%) mmHg in
SBP and -2.80 (-4.28, -1.32; I = 60%) mmHg in DBP. Pharmaceutical preparations of
N. sativa in powder and oil demonstrated a different lowering effect (in favour
of the former) on both SBP and DBP. No association was observed between SBP
lowering and time on treatment, N. sativa dosage or type of N. sativa. The
results of Egger's test did not indicate any publication bias. Our meta-analysis
suggests that short-term treatment with N. sativa powder can significantly reduce
SBP and DBP levels. More evidence is needed, however, to strengthen the available
evidence and to further explore the long-term BP-lowering effect of N. sativa.
PMID- 27512972
TI - Effects of pentoxifylline on inflammatory markers and blood pressure: a
systematic review and meta-analysis of randomized controlled trials.
AB - INTRODUCTION: Pentoxifylline is a xanthine derivative with potential
cardiovascular benefits. AIM: To evaluate the impact of pentoxifylline on blood
pressure (BP) and plasma TNF-alpha, C-reactive protein (CRP) and IL-6 through a
systematic review and meta-analysis of randomized controlled trials. METHODS: The
protocol was registered (PROSPERO: CRD42016035988). The search included PUBMED,
ProQuest, Scopus and EMBASE until 1 September 2015 to identify trials reporting
BP or inflammatory markers during pentoxifylline therapy. Quantitative data
synthesis was performed using a random-effects model, with weighted mean
difference (WDF) and 95% confidence intervals (CIs) as summary statistics.
RESULTS: Fifteen studies (16 treatment arms) were found to be eligible for
inclusion. Meta-analysis did not suggest any effect of pentoxifylline on either
SBP or DBP. Pentoxifylline treatment was associated with a significant reduction
in plasma concentrations of TNF-alpha (WDF: -1.03 pg/ml, 95% CI: -1.54, -0.51; P
< 0.001, 11 treatment arms) and CRP (WDF: -1.39 mg/l, 95% CI: -2.68, -0.10; P =
0.034, five treatment arms). No alteration in plasma IL-6 concentration was
observed. The impact of pentoxifylline on plasma TNF-alpha levels was found to be
positively associated with treatment duration (slope: 0.031; 95% CI: 0.004,
0.057; P = 0.023) but independent of pentoxifylline dose (slope: -0.0003; 95% CI:
-0.002, 0.001; P = 0.687). CONCLUSION: Pentoxifylline did not alter BP or plasma
IL-6 concentration, but significantly reduced circulating TNF-alpha and CRP
concentrations.
PMID- 27512973
TI - Accelerated progression of coronary artery calcification in hypertension but also
prehypertension.
AB - OBJECTIVE: To determine the role of hypertension for coronary artery
calcification (CAC) progression. METHODS: The population-based Heinz Nixdorf
Recall study recruited 4814 participants from a German urban population in 2000
2003. CAC was measured using electron-beam computed tomography at baseline and
after 5 years. The present analyses refer to 3481 participants with repeat scan
(coronary heart disease until 5 years excluded, age at baseline 45-74 years, and
53.1% women). Blood pressure (BP), Framingham risk factors, and antihypertensive
medication were recorded at baseline. BP was staged according to Joint National
Committee 7 guidelines. Participants under antihypertensive medication were
classified as stage 2. CAC at 5 years was predicted from baseline using our
dedicated, publicly available algorithm. CAC progression was accordingly
classified as slow, expected, or rapid. RESULTS: Normotension was found in 20.5%,
prehypertension in 27.2%, stage 1 hypertension in 15.8%, and stage 2 (ST2) in
36.5%. The frequency of rapid progression increases with BP stage (normotension:
16.7% to ST2: 21.1%, P = 0.004). Risk factor adjusted relative risk [RR (95%
confidence interval), reference: normotension] of rapid progression was for
prehypertension: 1.22 (0.98;1.51), stage 1: 1.29 (1.01;1.65), and ST2: 1.45
(1.17;1.79). Risk factor adjusted measures of CAC progression per 10 mmHg SBP
were already elevated in women with BP below 140/90 mmHg: CAC onset, RR = 1.22
(1.07;1.40), rapid progression, RR = 1.17 (1.05;1.31), 5-year CAC progression,
6.7% (0.5;13.4). In men below 140/90 mmHg, only RR of rapid progression was
considerably increased [RR = 1.11 (0.96;1.29)]. CONCLUSION: CAC progression, a
sign of ongoing target organ damage, is already accelerated in prehypertensive
patients, a substantial proportion of our urban population.
PMID- 27512974
TI - Elevated estimated arterial age is associated with metabolic syndrome and low
grade inflammation.
AB - BACKGROUND: Arterial age can be estimated from equations relating arterial
stiffness to age and blood pressure in large cohorts. We investigated whether
estimated arterial age (eAA) was elevated in patients with the metabolic syndrome
and/or known cardiovascular disease (CVD), which factors were associated with eAA
and whether eAA added prognostic information. METHODS: In 1993, 2366 study
participants, 41, 51, 61, and 71 years old, had traditional cardiovascular risk
factors and carotid-femoral pulse wave velocity (cfPWV) measured. Risk groups
were identified based on known CVD and components of metabolic syndrome,
Systematic COronary Risk Evaluation, or Framingham risk score. From age, mean
blood pressure, and cfPWV, eAA and estimated cfPWV (ePWV) were calculated. In
2006, the combined cardiovascular endpoint (CEP) of cardiovascular death,
nonfatal myocardial infarction, nonfatal stroke, and hospitalization for ischemic
heart disease was registered. RESULTS: cfPWV and ePWV increased with ageing and
cardiovascular risk (all P < 0.001), but ePWV increased more with ageing than
cfPWV. The difference between eAA and chronological age was associated with male
sex (beta = 0.14), higher heart rate (beta = 0.16 both P < 0.001), fasting
glucose (beta = 0.08) soluble urokinase plasminogen activator receptor (beta =
0.06, both P < 0.01), and known CVD (beta = 0.06, P < 0.05) independently of age,
SBP, and heart rate. Independently of Systematic COronary Risk Evaluation, eAA
(hazard ratio = 1.20, P < 0.01) predicted CEP, but not as accurately as ePWV
(hazard ratio = 1.58, P < 0.001) and cfPWV (hazard ratio = 1.32, P < 0.001) among
apparently healthy study participants. CONCLUSION: Elevated eAA was associated
with male sex, higher plasma glucose, and soluble urokinase plasminogen activator
receptor and known CVD independently of age, SBP, and heart rate.
PMID- 27512975
TI - Interrupting prolonged sitting with brief bouts of light walking or simple
resistance activities reduces resting blood pressure and plasma noradrenaline in
type 2 diabetes.
AB - OBJECTIVE: Prolonged sitting is increasingly recognized as a ubiquitous
cardiometabolic risk factor, possibly distinct from lack of physical exercise. We
examined whether interrupting prolonged sitting with brief bouts of light
intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2
diabetes (T2D). METHODS: In a randomized crossover trial, 24 inactive
overweight/obese adults with T2D (14 men; mean +/- SD; 62 +/- 6 years) consumed
standardized meals during 3 * 8 h conditions: uninterrupted sitting (SIT);
sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity
walking); and sitting + half-hourly bouts of simple resistance activities for 3
min (SRAs), each separated by 6-14 days washout. Resting seated BP was measured
hourly (mean of three recordings, >=20-min postactivity). Plasma noradrenaline
was measured at 30-min intervals for the first hour after meals and hourly
thereafter. RESULTS: Compared with SIT, mean resting SBP and DBP were
significantly reduced (P < 0.001) for both light-intensity walking (mean +/- SEM;
-14 +/- 1/-8 +/- 1 mmHg) and SRA (-16 +/- 1/-10 +/- 1 mmHg), with a more
pronounced effect for SRA (P < 0.05 versus light-intensity walking). Similarly,
mean plasma noradrenaline was significantly reduced for both light-intensity
walking (-0.3 +/- 0.1 nmol/l) and SRA (-0.6 +/- 0.1 nmol/l) versus SIT, with SRA
lower than light-intensity walking (P < 0.05). Mean resting heart rate was
lowered by light-intensity walking (-3 +/- 1 bpm; P < 0.05), but not SRA (-1 +/-
1 bpm). CONCLUSION: Interrupting prolonged sitting with brief bouts of light
intensity walking or SRA reduces resting BP and plasma noradrenaline in adults
with T2D, with SRA being more effective. Given the ubiquity of sedentary
behaviors and poor adherence to structured exercise, this approach may have
important implications for BP management in patients with T2D.
PMID- 27512976
TI - Metoclopramide unmasks potentially misleading contralateral suppression in
patients undergoing adrenal vein sampling for primary aldosteronism.
AB - OBJECTIVE: As metoclopramide stimulates aldosterone secretion, we tested its
usefulness in the assessment of lateralization of primary aldosteronism by
adrenal vein sampling (AVS). DESIGN: Prospective within-patient study in
consecutive patients undergoing AVS for primary aldosteronism subtyping. METHODS:
We compared the diagnostic accuracy of baseline and postmetoclopramide
lateralization index and relative (to cortisol) aldosterone secretion indices
(RASI) for each adrenal gland with aldosterone-producing adenoma (APA) determined
by the four corners criteria as the reference diagnosis. RESULTS: We recruited 93
consecutive patients (mean age: 52 years; women 31%). Metoclopramide increased
plasma aldosterone in the inferior vena cava and in both adrenal veins. The
postmetoclopramide lateralization index was accurate in identifying APA, but did
not increase diagnostic accuracy over baseline lateralization index, because the
RASI increased similarly in both sides. Conversely, metoclopramide raised RASI to
values more than 0.90 bilaterally in non-APA patients allowing accurate
identification of factitious aldosterone suppression. In contrast, RASI was 0.90
or less in 48% contralateral to the tumor in APA patients. Regression analysis
showed the APA patients with persistent suppression of RASI contralaterally
showed a more florid primary aldosteronism phenotype. CONCLUSION: Metoclopramide
does not enhance lateralization of aldosterone excess in APA, but consistently
increased the value of RASI in non-APA cases, thus unmasking potentially
misleading suppression of aldosterone. Postmetoclopramide RASI may therefore
allow a more precise diagnosis when AVS can be achieved only unilaterally.
PMID- 27512977
TI - Creatine kinase inhibition lowers systemic arterial blood pressure in
spontaneously hypertensive rats: a randomized controlled trial.
AB - OBJECTIVE: Creatine kinase is reported to be a main predictor of blood pressure
(BP) in the general population, with a strong correlation between resistance
artery creatine kinase expression and clinical BP in humans. The enzyme rapidly
regenerates ATP near cytoplasmic ATPases involved in pressor responses, including
resistance artery contractility and renal sodium retention. Therefore, we
assessed whether creatine kinase inhibition reduces BP. METHODS: We implemented
the 'Animal Research: Reporting of In Vivo Experiments' guideline. In a 4-week
randomized controlled trial, male 16-week-old spontaneously hypertensive rats (N
= 16) were randomly assigned to the specific competitive creatine kinase
inhibitor beta-guanidinopropionic acid (3%)-supplemented chow vs. standard chow.
BP measured by the tail-cuff method was the main outcome. Other outcomes included
vasodilation in isolated arteries and renal renin expression. RESULTS: Creatine
kinase inhibition reduced BP safely and reversibly. Mean baseline BP of,
respectively, 191.5 (standard error 4.3) mmHg SBP and 143.1 (4.1) mmHg DBP was
reduced by, respectively, 42.7 (5.5) mmHg SBP and 35.6 (5.0) mmHg DBP (P < 0.001)
compared with controls, with evidence of enhanced vasodilation and a diuretic
effect. CONCLUSION: To our knowledge, this is the first report on the BP-lowering
effect of creatine kinase inhibition. Our data indicate that modulation of the
creatine kinase system is a potential novel treatment target for hypertension.
PMID- 27512978
TI - C-reactive protein/oxidized low density lipoprotein/beta2-glycoprotein i
complexes induce lipid accumulation and inflammatory reaction in macrophages via
p38/mitogen-activated protein kinase and nuclear factor-kappaB signaling
pathways.
AB - Oxidized low-density lipoprotein (oxLDL) can bind to beta2-glycoprotein I
(beta2GPI) and C-reactive protein (CRP) to form stable complexes, which exert
certain effects in diabetic cardiovascular disease. A previous study by our group
has confirmed that the resulting complexes promote atherosclerosis in diabetic
BALB/c mice. The present study was designed to investigate the effects and
potential mechanisms of oxLDL complexes on lipid accumulation and inflammatory
reactions in RAW264.7 macrophages cultured in a hyperglycemic environment.
Cultured cells were divided into seven groups, which were treated with phosphate
buffered saline (control), CRP, beta2GPI, oxLDL, CRP/oxLDL, oxLDL/beta2GPI or
CRP/oxLDL/beta2GPI. The results revealed the formation of foam cells in the
oxLDL, CRP/oxLDL, oxLDL/beta2GPI as well as CRP/oxLDL/beta2GPI groups. Compared
with oxLDL, the three complexes induced less lipid accumulation (P<0.05) through
inhibiting the expression of CD36 mRNA and promoting the expression of and ABCG1
mRNA (P<0.05 vs. oxLDL). Furthermore, the levels of inflammatory factors
interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha were elevated in the
CRP/oxLDL and CRP/oxLDL/beta2GPI groups (P>0.05 vs. oxLDL), and obvious effects
on p38/mitogen-activated protein kinase and nuclear factor (NF)-kappaB
phosphorylation were also observed in these groups (P<0.05 vs. oxLDL). These
results suggested that CRP/oxLDL/betaG2P1 complexes may induce lipid accumulation
and inflammation in macrophages via the p38/MAPK and NF-kappaB signaling
pathways. However, some differences were observed between the complexes, which
may be attributed to the property of each constituent; therefore, further studies
are required.
PMID- 27512979
TI - Human Urinary Epithelial Cells as a Source of Engraftable Hepatocyte-Like Cells
Using Stem Cell Technology.
AB - Although several types of somatic cells have been reprogrammed into induced
pluripotent stem cells (iPSCs) and then differentiated to hepatocyte-like cells
(iHeps), the method for generating such cells from renal tubular epithelial cells
shed in human urine and transplanting them into animal livers has not been
described systematically. We report reprogramming of human urinary epithelial
cells into iPSCs and subsequent hepatic differentiation, followed by a detailed
characterization of the newly generated iHeps. The epithelial cells were
reprogrammed into iPSCs by delivering the pluripotency factors OCT3/4, SOX2,
KLF4, and MYC using methods that do not involve transgene integration, such as
nucleofection of episomal (oriP/EBNA-1) plasmids or infection with recombinant
Sendai viruses. After characterization of stable iPSC lines, a three-step
differentiation toward hepatocytes was performed. The iHeps expressed a large
number of hepatocyte-preferred genes, including nuclear receptors that regulate
genes involved in cholesterol homeostasis, bile acid transport, and
detoxification. MicroRNA profile of the iHeps largely paralleled that of primary
human hepatocytes. The iHeps engrafted into the livers of Scid mice transgenic
for mutant human SERPINA1 after intrasplenic injection. Thus, urine is a readily
available source for generating human iHeps that could be potentially useful for
disease modeling, pharmacological development, and regenerative medicine.
PMID- 27512980
TI - Fusion of foreign T-cell epitopes and addition of TLR agonists enhance immunity
against Neospora caninum profilin in cattle.
AB - We demonstrated recently that immunization with recombinant Neospora caninum
profilin (rNcPRO) induces limited protection and a regulatory T-cell response in
mice. The aim of this study was to evaluate the immune response elicited by
rNcPRO in cattle and assess a strategy to enhance its immunogenicity, combining
the addition of T-cell epitopes and immune modulators. We developed a chimeric
recombinant profilin fused to functional T-cell epitopes present in the N
terminal sequence of vesicular stomatitis virus (VSV) glycoprotein G (rNcPRO/G).
Groups of three cattle were immunized with two doses (2 weeks apart) of rNcPRO or
rNcPRO/G formulated with alum hydroxide or a nanoparticulated soya-based adjuvant
enriched with Toll-like receptor (TLR) 2 and TLR9 agonists, aimed to tackle the
MyD88 pathway (AVECplus). rNcPRO induced only a primary immune response (IgM
mediated), while antibodies in rNcPRO/G-vaccinated animals switched to IgG1 after
the booster. The vaccine formulated with rNcPRO/G and AVECplus improved the
production of systemic IFN-gamma and induced long-term recall B-cell responses.
Overall, our study provides data supporting the use of T-cell epitopes from VSV
glycoprotein G and TLR agonists to enhance and modulate immunity to peptide
antigens in bovines, particularly when using small proteins from parasites for
which immune responses are usually feeble.
PMID- 27512982
TI - Incidentally Diagnosed Intracranial Sewing Needle in an Adult Patient: A Failed
Infanticide Attempt?
PMID- 27512981
TI - Acid Sphingomyelinase (ASM) is a Negative Regulator of Regulatory T Cell (Treg)
Development.
AB - BACKGROUND/AIMS: Regulatory T cell (Treg) is required for the maintenance of
tolerance to various tissue antigens and to protect the host from autoimmune
disorders. However, Treg may, indirectly, support cancer progression and
bacterial infections. Therefore, a balance of Treg function is pivotal for
adequate immune responses. Acid sphingomyelinase (ASM) is a rate limiting enzyme
involved in the production of ceramide by breaking down sphingomyelin. Previous
studies in T-cells have suggested that ASM is involved in CD28 signalling, T
lymphocyte granule secretion, degranulation, and vesicle shedding similar to the
formation of phosphatidylserine-exposing microparticles from glial cells.
However, whether ASM affects the development of Treg has not yet been described.
METHODS: Splenocytes, isolated Naive T lymphocytes and cultured T cells were
characterized for various immune T cell markers by flow cytometery. Cell
proliferation was measured by Carboxyfluorescein succinimidyl ester (CFSE) dye,
cell cycle analysis by Propidium Iodide (PI), mRNA transcripts by q-RT PCR and
protein expression by Western Blotting respectively. RESULTS: ASM deficient mice
have higher number of Treg compared with littermate control mice. In vitro
induction of ASM deficient T cells in the presence of TGF-beta and IL-2 lead to a
significantly higher number of Foxp3+ induced Treg (iTreg) compared with control
T-cells. Further, ASM deficient iTreg has less AKT (serine 473) phosphorylation
and Rictor levels compared with control iTreg. Ceramide C6 led to significant
reduction of iTreg in both ASM deficient and WT mice. The reduction in iTreg
leads to induction of IL-1beta, IL-6 and IL-17 but not IFN-gamma mRNA levels.
CONCLUSION: ASM is a negative regulator of natural and iTreg.
PMID- 27512983
TI - Are new antibiotics better than beta-lactams for non-critical inpatients with
community-acquired pneumonia?
AB - Treatment for community-acquired pneumonia in immunocompetent adults is mainly
empirical. Beta-lactam antibiotics have been traditionally considered first-line
therapy. New antibiotics could be more effective but the evidence is not clear
until now, and its use could entail greater costs, an increase in bacterial
resistance and other adverse effects. Searching in Epistemonikos database, which
is maintained by screening 30 databases, we identified six systematic reviews
including 36 randomized trials addressing this question. We combined the evidence
using meta-analysis and generated a summary of findings table following the GRADE
approach. We concluded new antibiotics are not better than beta-lactam
antibiotics for the treatment of non-critical inpatients with community-acquired
pneumonia in relation to clinical failure or adverse effects.
PMID- 27512985
TI - 10-Methyldodecanal, a Novel Attractant Pheromone Produced by Males of the South
American Cerambycid Beetle Eburodacrys vittata.
AB - We report the identification, synthesis, and field bioassay of a novel attractant
pheromone produced by males of Eburodacrys vittata (Blanchard), a South American
cerambycid beetle in the subfamily Cerambycinae. Headspace volatiles from males
contained a sex-specific compound, identified as 10-methyldodecanal. In a field
bioassay conducted in Brazil, significant numbers of males and females were
caught in traps baited with synthesized racemic 10-methyldodecanal, consistent
with the aggregation-sex pheromones produced by males of many cerambycine
species. This compound represents a new structural class of cerambycid
pheromones, and it is the first pheromone identified for a species in the tribe
Eburiini.
PMID- 27512984
TI - Combating a Global Threat to a Clonal Crop: Banana Black Sigatoka Pathogen
Pseudocercospora fijiensis (Synonym Mycosphaerella fijiensis) Genomes Reveal
Clues for Disease Control.
AB - Black Sigatoka or black leaf streak disease, caused by the Dothideomycete fungus
Pseudocercospora fijiensis (previously: Mycosphaerella fijiensis), is the most
significant foliar disease of banana worldwide. Due to the lack of effective host
resistance, management of this disease requires frequent fungicide applications,
which greatly increase the economic and environmental costs to produce banana.
Weekly applications in most banana plantations lead to rapid evolution of
fungicide-resistant strains within populations causing disease-control failures
throughout the world. Given its extremely high economic importance, two strains
of P. fijiensis were sequenced and assembled with the aid of a new genetic
linkage map. The 74-Mb genome of P. fijiensis is massively expanded by LTR
retrotransposons, making it the largest genome within the Dothideomycetes.
Melting-curve assays suggest that the genomes of two closely related members of
the Sigatoka disease complex, P. eumusae and P. musae, also are expanded.
Electrophoretic karyotyping and analyses of molecular markers in P. fijiensis
field populations showed chromosome-length polymorphisms and high genetic
diversity. Genetic differentiation was also detected using neutral markers,
suggesting strong selection with limited gene flow at the studied geographic
scale. Frequencies of fungicide resistance in fungicide-treated plantations were
much higher than those in untreated wild-type P. fijiensis populations. A
homologue of the Cladosporium fulvum Avr4 effector, PfAvr4, was identified in the
P. fijiensis genome. Infiltration of the purified PfAVR4 protein into leaves of
the resistant banana variety Calcutta 4 resulted in a hypersensitive-like
response. This result suggests that Calcutta 4 could carry an unknown resistance
gene recognizing PfAVR4. Besides adding to our understanding of the overall
Dothideomycete genome structures, the P. fijiensis genome will aid in developing
fungicide treatment schedules to combat this pathogen and in improving the
efficiency of banana breeding programs.
PMID- 27512986
TI - Ingenol Mebutate 150 mg as Physician-Directed Treatment of Bowen's Disease Under
Occlusion.
AB - Ingenol mebutate (IM) is a topical pharmacotherapy approved in Switzerland since
2012 for treating non-hypertrophic, non-hyperkeratotic actinic keratosis. We
report a case with off-label use of IM where Bowen's disease has been
successfully treated with physician-directed IM 0.015% gel under occlusion over
the chest area.
PMID- 27512987
TI - Correction: Associations of C-Reactive Protein, Granulocytes and Granulocyte-to
Lymphocyte Ratio with Mortality from Breast Cancer in Non-Institutionalized
American Women.
AB - [This corrects the article DOI: 10.1371/journal.pone.0157482.].
PMID- 27512989
TI - HBV-Associated Postinfectious Acute Glomerulonephritis: A Report of 10 Cases.
AB - Postinfectious acute glomerulonephritis (PIGN) may occur after various bacterial
and viral infections. Hepatitis B virus (HBV) infection is a cause of chronic
glomerulonephritis. We report here 10 cases (ages 7-20 years-old) of chronic HBV
carriers with acute glomerulonephritis, with positive glomerular staining of
hepatitis B surface antigen, and detectable presence of HBV DNA in the glomeruli.
This form of PIGN, HBV-PIGN, has not been previously identified. To further
characterize clinical and pathological features of HBV- PIGN, we selected 10
cases of age-matched non-HBV PIGN for comparison. While both HBV associated PIGN
and non-HBV PIGN similarly presented as proteinuria, hematuria, and hypertension,
there was a trend of higher acute kidney injury and worsened prognosis in HBV
PIGN. 6 months after the onset, 4 patients with HBV associated PIGN did not show
improvement from the disease, whereas all patients with non-HBV PIGN had complete
or partial recovery. Pathologically, both HBV associated PIGN and non-HBV PIGN
showed typical diffuse glomerular endocapillary proliferation, but HBV associated
PIGN differed from classical PIGN with much fewer sub-epithelial glomerular "hump
shape" immune complex depositions. In conclusion, we have identified a novel
association of HBV infection with acute glomerulonephritis.
PMID- 27512988
TI - The Invalidation of HspB1 Gene in Mouse Alters the Ultrastructural Phenotype of
Muscles.
AB - Even though abundance of Hsp27 is the highest in skeletal muscle, the
relationships between the expression of HspB1 (encoding Hsp27) and muscle
characteristics are not fully understood. In this study, we have analysed the
effect of Hsp27 inactivation on mouse development and phenotype. We generated a
mouse strain devoid of Hsp27 protein by homologous recombination of the HspB1
gene. The HspB1-/- mouse was viable and fertile, showing neither apparent
morphological nor anatomical alterations. We detected a gender dimorphism with
marked effects in males, a lower body weight (P < 0.05) with no obvious changes
in the growth rate, and a lower plasma lipids profile (cholesterol, HDL and
triglycerides, 0.001 < P< 0.05). The muscle structure of the animals was examined
by optical microscopy and transmission electron microscopy. Not any differences
in the characteristics of muscle fibres (contractile and metabolic type, shape,
perimeter, cross-sectional area) were detected except a trend for a higher
proportion of small fibres. Different myosin heavy chains electrophoretic
profiles were observed in the HspB1-/- mouse especially the presence of an
additional isoform. Electron microscopy revealed ultrastructural abnormalities in
the myofibrillar structure of the HspB1-/- mouse mutant mice (e.g. destructured
myofibrils and higher gaps between myofibrils) especially in the m. Soleus.
Combined with our previous data, these findings suggest that Hsp27 could directly
impact the organization of muscle cytoskeleton at the molecular and
ultrastructural levels.
PMID- 27512990
TI - Altered Vision-Related Resting-State Activity in Pituitary Adenoma Patients with
Visual Damage.
AB - OBJECTIVE: To investigate changes of vision-related resting-state activity in
pituitary adenoma (PA) patients with visual damage through comparison to healthy
controls (HCs). METHODS: 25 PA patients with visual damage and 25 age- and sex
matched corrected-to-normal-vision HCs underwent a complete neuro-ophthalmologic
evaluation, including automated perimetry, fundus examinations, and a magnetic
resonance imaging (MRI) protocol, including structural and resting-state fMRI (RS
fMRI) sequences. The regional homogeneity (ReHo) of the vision-related cortex and
the functional connectivity (FC) of 6 seeds within the visual cortex (the primary
visual cortex (V1), the secondary visual cortex (V2), and the middle temporal
visual cortex (MT+)) were evaluated. Two-sample t-tests were conducted to
identify the differences between the two groups. RESULTS: Compared with the HCs,
the PA group exhibited reduced ReHo in the bilateral V1, V2, V3, fusiform, MT+,
BA37, thalamus, postcentral gyrus and left precentral gyrus and increased ReHo in
the precuneus, prefrontal cortex, posterior cingulate cortex (PCC), anterior
cingulate cortex (ACC), insula, supramarginal gyrus (SMG), and putamen. Compared
with the HCs, V1, V2, and MT+ in the PAs exhibited decreased FC with the V1, V2,
MT+, fusiform, BA37, and increased FC primarily in the bilateral temporal lobe
(especially BA20,21,22), prefrontal cortex, PCC, insular, angular gyrus, ACC, pre
SMA, SMG, hippocampal formation, caudate and putamen. It is worth mentioning that
compared with HCs, V1 in PAs exhibited decreased or similar FC with the thalamus,
whereas V2 and MT+ exhibited increased FCs with the thalamus, especially
pulvinar. CONCLUSIONS: In our study, we identified significant neural
reorganization in the vision-related cortex of PA patients with visual damage
compared with HCs. Most subareas within the visual cortex exhibited remarkable
neural dysfunction. Some subareas, including the MT+ and V2, exhibited enhanced
FC with the thalamic pulvinar, which indicates an important role in the
compensatory mechanism following visual impairment. In addition, neural
dysfunction within the visual cortex was associated with neural activity
alternation in the higher-order cognitive cortex, especially subareas in default
mode network (DMN) and salience network (SN).
PMID- 27512991
TI - Role of SpdA in Cell Spreading and Phagocytosis in Dictyostelium.
AB - Dictyostelium discoideum is a widely used model to study molecular mechanisms
controlling cell adhesion, cell spreading on a surface, and phagocytosis. In this
study we isolated and characterize a new mutant created by insertion of a
mutagenic vector in the heretofore uncharacterized spdA gene. SpdA-ins mutant
cells produce an altered, slightly shortened version of the SpdA protein. They
spread more efficiently than WT cells when allowed to adhere to a glass
substrate, and phagocytose particles more efficiently. On the contrary, a
functional spdA knockout mutant where a large segment of the gene was deleted
phagocytosed less efficiently and spread less efficiently on a substrate. These
phenotypes were highly dependent on the cellular density, and were most visible
at high cell densities, where secreted quorum-sensing factors inhibiting cell
motility, spreading and phagocytosis are most active. These results identify the
involvement of SpdA in the control of cell spreading and phagocytosis. The
underlying molecular mechanisms, as well as the exact link between SpdA and cell
spreading, remain to be established.
PMID- 27512992
TI - Higher Ammonium Transamination Capacity Can Alleviate Glutamate Inhibition on
Winter Wheat (Triticum aestivum L.) Root Growth under High Ammonium Stress.
AB - Most of the studies about NH4+ stress mechanism simply address the effects of
free NH4+, failing to recognize the changed nitrogen assimilation products. The
objective of this study was to elucidate the effects of glutamate on root growth
under high ammonium (NH4+) conditions in winter wheat (Triticum aestivum L.).
Hydroponic experiments were conducted using two wheat cultivars, AK58 (NH4+
sensitive) and Xumai25 (NH4+-tolerant) with either 5 mM NH4+ nitrogen (AN) as
stress treatment or 5 mM nitrate (NO3-) nitrogen as control. To evaluate the
effects of NH4+-assimilation products on plant growth, 1 MUM L-methionine
sulfoximine (MSO) (an inhibitor of glutamine synthetase (GS)) and 1 mM glutamates
(a primary N assimilation product) were added to the solutions, respectively. The
AN significantly reduced plant biomass, total root length, surface area and root
volume in both cultivars, but less effect was observed in Xumai25. The inhibition
effects were alleviated by the application of MSO but strengthened by the
application of glutamate. The AN increased the activities of GS, glutamate
dehydrogenase (GDH) in both cultivars, resulting in higher glutamate contents.
However, its contents were decreased by the application of MSO. Compared to AK58,
Xumai25 showed lower glutamate contents due to its higher activities of glutamic
oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT). With the
indole-3-acetic acid (IAA) contents decreasing in roots, the ratio of shoot to
root in IAA was increased, and further increased by the application of glutamate,
and reduced by the application of MSO, but the ratio was lower in Xumai25.
Meanwhile, the total soluble sugar contents and its root to shoot ratio also
showed similar trends. These results indicate that the NH4+-tolerant cultivar has
a greater transamination ability to prevent glutamate over-accumulation to
maintain higher IAA transport ability, and consequently promoted soluble sugar
transport to roots, further maintaining root growth.
PMID- 27512993
TI - Keratin 17 Is Induced in Oral Cancer and Facilitates Tumor Growth.
AB - Keratin subtypes are selectively expressed depending on the cell type. They not
only provide structural support, but regulate the metabolic processes and
signaling pathways that control the growth of the epithelium. KRT17 (keratin 17)
is induced in the regenerative epithelium and acts on diverse signaling pathways.
Here, we demonstrate that KRT17 is invariably and permanently induced in oral
squamous cell carcinoma (OSCC), as revealed by immunohistochemistry and cDNA
microarray analysis. Two representative OSCC cell lines; KRT17-weakly expressing
Ca9-22 and KRT17-highly expressing HSC3 were used to establish KRT17
overexpressing Ca9-22 and KRT17-knockdown HSC3 cells. Analysis of these cells
revealed that KRT17 promoted cell proliferation and migration by stimulating the
Akt/mTOR pathway. KRT17 also upregulated the expression of SLC2A1 (solute carrier
family 2 member 1/Glut1) and glucose uptake. To further investigate the effect of
KRT17 on tumorigenesis, KRT17-knockout HSC3 cells were established and were
transplanted to the cephalic skin of nude mice. The tumors that developed from
KRT17-knockout HSC3 cells had a lower Ki-67 labeling index and were significantly
smaller compared to the controls. These results indicate that KRT17 stimulates
the Akt/mTOR pathway and glucose uptake, thereby facilitating tumor growth. We
could not confirm the relationship between KRT17 and SFN (stratifin) in the cells
examined in this study. However, our study reinforces the concept that the
cellular properties of cancer are regulated by a series of molecules similar to
those found in wound healing. In OSCC, KRT17 acts as a pathogenic keratin that
facilitates tumor growth through the stimulation of multiple signaling pathways,
highlighting the importance of KRT17 as a multifunctional promoter of
tumorigenesis.
PMID- 27512994
TI - A Cost-Effectiveness Tool to Guide the Prioritization of Interventions for
Rheumatic Fever and Rheumatic Heart Disease Control in African Nations.
AB - BACKGROUND: Rheumatic heart disease (RHD) prevalence and mortality rates remain
especially high in many parts of Africa. While effective prevention and treatment
exist, coverage rates of the various interventions are low. Little is known about
the comparative cost-effectiveness of different RHD interventions in limited
resource settings. We developed an economic evaluation tool to assist ministries
of health in allocating resources and planning RHD control programs.
METHODOLOGY/PRINCIPAL FINDINGS: We constructed a Markov model of the natural
history of acute rheumatic fever (ARF) and RHD, taking transition probabilities
and intervention effectiveness data from previously published studies and expert
opinion. Our model estimates the incremental cost-effectiveness of scaling up
coverage of primary prevention (PP), secondary prevention (SP) and heart valve
surgery (VS) interventions for RHD. We take a healthcare system perspective on
costs and measure outcomes as disability-adjusted life-years (DALYs), discounting
both at 3%. Univariate and probabilistic sensitivity analyses are also built into
the modeling tool. We illustrate the use of this model in a hypothetical low
income African country, drawing on available disease burden and cost data. We
found that, in our hypothetical country, PP would be cost saving and SP would be
very cost-effective. International referral for VS (e.g., to a country like India
that has existing surgical capacity) would be cost-effective, but building in
country VS services would not be cost-effective at typical low-income country
thresholds. CONCLUSIONS/SIGNIFICANCE: Our cost-effectiveness analysis tool is
designed to inform priorities for ARF/RHD control programs in Africa at the
national or subnational level. In contrast to previous literature, our
preliminary findings suggest PP could be the most efficient and cheapest approach
in poor countries. We provide our model for public use in the form of a
Supplementary File. Our research has immediate policy relevance and calls for
renewed efforts to scale up RHD prevention.
PMID- 27512995
TI - Thrombomodulin Influences the Survival of Patients with Non-Metastatic Colorectal
Cancer through Epithelial-To-Mesenchymal Transition (EMT).
AB - BACKGROUND: Treatment resistance and metastasis are the major causes of death
among patients with colorectal cancer (CRC). Approximately 20% of surgically
treated patients ultimately develop metastases during the follow-up period.
Currently, the TNM system is the only available prognostic test. Therefore, the
identification of new markers for CRC remains important. Thrombomodulin (TM), a
glycoprotein, is involved in angiogenesis and has been linked to many malignant
diseases. However, the function of TM in CRC remains unclear. METHODS: A total of
170 patients with CRC participated in this study. TM expression was analyzed via
immunohistochemistry. Univariate (Kaplan-Meier) analysis was used to analyze
patient outcomes, including overall survival (OS) and disease-free survival
(DFS). TM expression was manipulated using shRNA or an overexpression system.
Transwell migration assays, wound healing migration assays, and the xCELLigence
biosensor system were used to detect cell proliferative and migratory capacities.
RESULTS: TM expression in the tumor tissues significantly and positively
correlated with the DFS and OS of non-metastatic patients with CRC (ps = 0.036
and 0.0218, respectively). Suppression of TM expression increased the
proliferation and migration of DLD-1 cells. TM overexpression reduced the cells'
proliferative and migratory capacities. Cyclooxygenase (COX)-2 expression was up
regulated following TM silencing. Furthermore, the association between the
migration of colon cancer cells and the levels of TM and epithelial-to
mesenchymal transition (EMT) markers (fibronectin, vimentin and ezrin) was
confirmed in HT29 and DLD-1 cells. CONCLUSIONS: Our study demonstrates that
patients with non-metastatic CRC display low TM expression in their tumors and
exhibit reduced DFS and OS. The enhanced expression of mesenchymal markers and
COX-2 may be involved in the mechanisms that underlie recurrence in patients with
cancer displaying low TM expression.
PMID- 27512996
TI - Incidence of X and Y Chromosomal Aneuploidy in a Large Child Bearing Population.
AB - BACKGROUND: X&Y chromosomal aneuploidies are among the most common human whole
chromosomal copy number changes, but the population-based incidence and
prevalence in the child-bearing population is unclear. METHODS: This
retrospective analysis of prospectively collected data leveraged a routine non
invasive prenatal test (NIPT) using parental genotyping to estimate the
population-based incidence of X&Y chromosome variations in this population
referred for NIPT (generally due to advanced maternal age). RESULTS: From 141,916
women and 29,336 men, 119 X&Y chromosomal abnormalities (prevalence: 1 in 1,439)
were identified. Maternal findings include: 43 cases of 45,X (40 mosaic); 30
cases of 47,XXX (12 mosaic); 3 cases of 46,XX uniparental disomy; 2 cases of
46,XY/46,XX; 23 cases of mosaicism of unknown type; 2 cases of 47,XX,i(X)(q10).
Paternal findings include: 2 cases of 47,XXY (1 mosaic); 10 cases of 47,XYY (1
mosaic); 4 partial Y deletions. CONCLUSIONS: Single chromosome aneuploidy was
present in one of every 1,439 individuals considered in this study, showing
47,XXX; 47,XX,i(X)(q10); 47,XYY; 47,XXY, partial Y deletions, and a high level of
mosaicism for 45,X. This expands significantly our understanding of X&Y
chromosomal variations and fertility issues, and is critical for families and
adults affected by these disorders. This current and extensive information on
fertility will be beneficial for genetic counseling on prenatal diagnoses as well
as for newly diagnosed postnatal cases.
PMID- 27512997
TI - Understanding the Pathogenicity of Burkholderia contaminans, an Emerging Pathogen
in Cystic Fibrosis.
AB - Several bacterial species from the Burkholderia cepacia complex (Bcc) are feared
opportunistic pathogens that lead to debilitating lung infections with a high
risk of developing fatal septicemia in cystic fibrosis (CF) patients. However,
the pathogenic potential of other Bcc species is yet unknown. To elucidate
clinical relevance of Burkholderia contaminans, a species frequently isolated
from CF respiratory samples in Ibero-American countries, we aimed to identify its
key virulence factors possibly linked with an unfavorable clinical outcome. We
performed a genome-wide comparative analysis of two isolates of B. contaminans
ST872 from sputum and blood culture of a female CF patient in Argentina. RNA-seq
data showed significant changes in expression for quorum sensing-regulated
virulence factors and motility and chemotaxis. Furthermore, we detected
expression changes in a recently described low-oxygen-activated (lxa) locus which
encodes stress-related proteins, and for two clusters responsible for the
biosynthesis of antifungal and hemolytic compounds pyrrolnitrin and
occidiofungin. Based on phenotypic assays that confirmed changes in motility and
in proteolytic, hemolytic and antifungal activities, we were able to distinguish
two phenotypes of B. contaminans that coexisted in the host and entered her
bloodstream. Whole genome sequencing revealed that the sputum and bloodstream
isolates (each representing a distinct phenotype) differed by over 1,400
mutations as a result of a mismatch repair-deficient hypermutable state of the
sputum isolate. The inferred lack of purifying selection against nonsynonymous
mutations and the high rate of pseudogenization in the derived isolate indicated
limited evolutionary pressure during evolution in the nutrient-rich, stable CF
sputum environment. The present study is the first to examine the genomic and
transcriptomic differences between longitudinal isolates of B. contaminans.
Detected activity of a number of putative virulence factors implies a genuine
pathogenic nature of this novel Bcc species.
PMID- 27512998
TI - Re-Cloning the N27 Dopamine Cell Line to Improve a Cell Culture Model of
Parkinson's Disease.
AB - Parkinson's disease is characterized by the death of dopaminergic neurons in the
substantia nigra. To understand the molecular mechanisms of the disease, an in
vitro model is important. In the 1990s, we used the SV40 large T antigen to
immortalize dopaminergic neurons derived from Embryonic Day 14 rat mesencephalon.
We selected a clone for its high expression of dopaminergic neuron markers such
as tyrosine hydroxylase (TH), and we named it 1RB3AN27 (N27). Because the
original N27 cell line has been passaged many times, the line has become a
mixture of cell types with highly variable expression of TH. In the current
study, we have performed multiple rounds of clonal cultures and have identified a
dopaminergic cell clone expressing high levels of TH and the dopamine transporter
(DAT). We have named this new clone N27-A. Nearly 100% of N27-A cells express TH,
DAT and Tuj1. Western blots have confirmed that N27-A cells have three to four
times the levels of TH and DAT compared to the previous mixed population in N27.
Further analysis has shown that the new clone expresses the dopamine neuron
transcription factors Nurr1, En1, FoxA2 and Pitx3. The N27-A cells express the
vesicular monoamine transporter (VMAT2), but do not express dopamine-beta
hydroxylase (DbetaH), the enzyme responsible for converting dopamine to
norepinephrine. Functional analysis has shown that N27-A cells are more sensitive
than N27 cells to neurotoxins taken up by the dopamine transporter such as 6
hydroxydopamine and 1-methyl-4-phenylpyridine (MPP+). The DAT inhibitor
nomifensine can block MPP+ induced toxicity. The non-selective toxic effects of
hydrogen peroxide were similar in both cell lines. The N27-A cells show dopamine
release under basal and depolarization conditions. We conclude that the new N27-A
clone of the immortalized rat dopaminergic cell line N27 should provide an
improved in vitro model for Parkinson's disease research.
PMID- 27512999
TI - The Mass Loss and Humification of Stumps and Roots in Masson Pine Plantations
Based on Log File Records.
AB - Stumps account for a large proportion of coarse woody debris in managed forests,
but their decay dynamics are poorly understood. The loss of mass and the degree
of humification of the above-ground woody debris, below-ground woody debris, bark
and root system (R1, 10 mm >= diameter > 0 mm; R2, 25 mm >= diameter >10 mm; 100
mm >= R3 > 25 mm; R4 > 100 mm) of Masson pine (Pinus massoniana) stump systems
were evaluated in southwestern China in a chronosequence of plantations cut 1-15
years prior to the study. The results indicated that above-ground woody debris
decomposed more quickly than below-ground woody debris and bark, whereas the
degree of humification followed the opposite trend. Compared with one-year
stumps, the mass losses of 15-year stump systems were 60.4% for above-ground
woody debris, 42.1% for below-ground woody debris, 47.3% for bark, 69.9% for R1,
47.3% for R2, 51.0% for R3, and 83.2% for R4. In contrast, below-ground woody
debris showed a greater degree of humification compared with other components in
the stump system. Among the root system, fine roots (R1, diameter <= 10 mm) had
the largest k value (0.09), whereas the decay rate of coarser roots (R2, R3, R4;
diameter > 10 mm) increased with increasing root diameter. However, coarse roots
showed a larger degree of humification (0.2-0.6) than fine roots (0.3-0.4). These
results suggest that below-ground woody debris and coarse roots may display a
higher degree of humification, showing greater short-term contributions to
overall humification when compared with the other components in the stump system.
PMID- 27513000
TI - PSO-Based Smart Grid Application for Sizing and Optimization of Hybrid Renewable
Energy Systems.
AB - This paper introduces an optimal sizing algorithm for a hybrid renewable energy
system using smart grid load management application based on the available
generation. This algorithm aims to maximize the system energy production and meet
the load demand with minimum cost and highest reliability. This system is formed
by photovoltaic array, wind turbines, storage batteries, and diesel generator as
a backup source of energy. Demand profile shaping as one of the smart grid
applications is introduced in this paper using load shifting-based load priority.
Particle swarm optimization is used in this algorithm to determine the optimum
size of the system components. The results obtained from this algorithm are
compared with those from the iterative optimization technique to assess the
adequacy of the proposed algorithm. The study in this paper is performed in some
of the remote areas in Saudi Arabia and can be expanded to any similar regions
around the world. Numerous valuable results are extracted from this study that
could help researchers and decision makers.
PMID- 27513001
TI - The Effect of Afforestation on Soil Moisture Content in Northeastern China.
AB - Widespread afforestation programs sequester carbon from the atmosphere and
mitigate the rising of atmospheric carbon dioxide (CO2). Meanwhile, afforestation
carbon sequestration may cost soil water. However, changes in soil moisture
content (SMC) after large-scale afforestation or reforestation have rarely been
quantified. In this study, we measured changes in SMC following afforestation
using a paired plots method with data from 757 plots in Northeastern China. We
found a marginally significant decline in soil moisture content of the top 1-m
soil (SMC0-1m) after afforestation (P = 0.08) at the regional scale. The SMC
responses to afforestation also vary across species. For example, significant SMC
decrease are found for Populus spp. plantations (P < 0.05) and plantations of
Pinus sylvestris var. mongolica (P < 0.05). Splitting the first meter of the soil
profile into different depth intervals revealed that SMC declined significantly
in shallow layers (0-30 cm) for Populus spp. and Pinus sylvestris var. mongolica.
We also found that when SMC in the control exceeded a specific threshold, SMC for
all five tree species considered tended to decrease, suggesting that the effects
of afforestation on soil hydrology vary across different regions.
PMID- 27513002
TI - Association of grade configuration with school climate for 7th and 8th grade
students.
AB - Educational authorities have questioned whether middle schools provide the best
school climate for 7th and 8th grade students, and proposed that other grade
configurations such as K-8th grade schools may provide a better learning
environment. The purpose of this study was to compare 7th and 8th grade students'
perceptions of 4 key features of school climate (disciplinary structure, student
support, student engagement, and prevalence of teasing and bullying) in middle
schools versus elementary or high schools. Multilevel multivariate modeling in a
statewide sample of 39,036 7th and 8th grade students attending 418 schools
revealed that students attending middle schools had a more negative perception of
school climate than students in schools with other grade configurations. Seventh
grade students placed in middle schools reported lower disciplinary structure and
a higher prevalence of teasing and bullying in comparison to those in elementary
schools. Eighth grade students in middle schools reported poorer disciplinary
structure, lower student engagement, and a higher prevalence of teasing and
bullying compared to those in high schools. These findings can guide school
psychologists in identifying aspects of school climate that may be troublesome
for 7th and 8th grade students in schools with different grade configurations.
(PsycINFO Database Record
PMID- 27513004
TI - Synthesis of 3-Cyano-1H-indoles and Their 2'-Deoxyribonucleoside Derivatives
through One-Pot Cascade Reactions.
AB - An efficient and economical synthetic approach toward 3-cyano-1H-indoles through
the reactions of 2-(2-bromophenyl)acetonitriles with aldehydes and aqueous
ammonia is presented. Mechanically, this novel protocol involves a one-pot
cascade procedure consisting of an aldol-type condensation, a copper-catalyzed
amination by using aqueous ammonia as a cheap and safe nitrogen source, and an
intramolecular Michael addition followed by a dehydrogenative aromatization.
Interestingly, the indole products thus obtained were found to be ready
substrates for the preparation of indole 2'-deoxyribonucleosides through an
unprecedented and highly practical glycosylation procedure in which the required
C-N bond formation and toluoyl protecting group removal were accomplished
efficiently in one pot.
PMID- 27513005
TI - Origin and Luminescence of Anomalous Red-Emitting Center in Rhombohedral
Ba9Lu2Si6O24:Eu(2+) Blue Phosphor.
AB - We obtain a blue phosphor, Ba9Lu2Si6O24:Eu(2+) (BLS:Eu(2+)), which shows a strong
emission peak at 460 nm and a weak tail from 460 to 750 nm. A 610 nm red emission
is observed for the first time in this kind of rhombohedral structure material,
which is much different from the same crystal structure of Ba9Sc2Si6O24:Eu(2+)
and Ba9Y2Si6O24:Eu(2+). The luminescence properties and decays from 10 to 550 K
are discussed. The new red emission arises from a trapped exciton state of Eu(2+)
at the Ba site with a larger coordination number (12-fold). It exhibits abnormal
luminescence properties with a broad bandwidth and a large Stokes shift. Under
the 400 nm excitation, the external quantum efficiency of BLS:Eu(2+) is 45.4%,
which is higher than the 35.7% for the commercial blue phosphor BAM:Eu(2+). If
the thermal stability of BLS:Eu(2+) can be improved, it will show promising
applications in efficient near-UV-based white LEDs.
PMID- 27513007
TI - The Silicon Version of Phosphine Chalcogenides: Synthesis and Bonding Analysis of
Stabilized Heavy Silaaldehydes.
AB - The synthesis of chalcogena-silaaldehydes (Ch = S, Se, Te), 15, stabilized by
interaction with N-heterocylic carbenes (NHCs) is reported. Compounds 15 are
formed by reaction of the NHC-stabilized hydridosilylene 13a with elemental
chalcogens in moderate yields. X-ray diffraction analysis of all three variants
of the chalcogena-silaaldehydes, 15, revealed short Si/Ch distances which are
close to expected values for Si?Ch double bonds. The results of natural bond
orbital and natural resonance theory analyses indicate strongly polarized Si-Ch
bonds and suggest the occurrence of negative hyperconjugation, which is
responsible for the short Si/Ch distances. These results indicate the isolobal
relation between NHC-stabilized heavy silaaldehydes 15 and the well-known
phosphine chalcogenides, R3PCh.
PMID- 27513006
TI - Identification of a Cyanine-Dye Labeled Peptidic Ligand for Y1R and Y4R, Based
upon the Neuropeptide Y C-Terminal Analogue, BVD-15.
AB - Traceable truncated Neuropeptide Y (NPY) analogues with Y1 receptor (Y1R)
affinity and selectivity are highly desirable tools in studying receptor
location, regulation, and biological functions. A range of fluorescently labeled
analogues of a reported Y1R/Y4R preferring ligand BVD-15 have been prepared and
evaluated using high content imaging techniques. One peptide, [Lys(2)(sCy5),
Arg(4)]BVD-15, was characterized as an Y1R antagonist with a pKD of 7.2 measured
by saturation analysis using fluorescent imaging. The peptide showed 8-fold lower
affinity for Y4R (pKD = 6.2) and was a partial agonist at this receptor. The
suitability of [Lys(2)(sCy5), Arg(4)]BVD-15 for Y1R and Y4R competition binding
experiments was also demonstrated in intact cells. The nature of the label was
shown to be critical with replacement of sCy5 by the more hydrophobic Cy5.5
resulting in a switch from Y1R antagonist to Y1R partial agonist.
PMID- 27513008
TI - Human Toll-like Receptor (TLR) 8-Specific Agonistic Activity in Substituted
Pyrimidine-2,4-diamines.
AB - Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine
profile favoring the generation of Type 1 helper T cells. A multiplexed high
throughput screen had led to the identification of N(4)-butyl-5-iodo-6
methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure
activity relationship study of this chemotype was undertaken. A butyl substituent
at N(4) was optimal, and replacement of the 5-iodo group with chloro, bromo, or
fluoro groups led to losses in potency, as did the introduction of aromatic bulk.
Drawing from our previous structure-based design, several 5-alkylamino
derivatives were evaluated. Significant enhancement of potency was achieved in 5
(4-aminobutyl)-N(4)-butyl-6-methylpyrimidine-2,4-diamine. This compound potently
induced Th1-biasing IFN-gamma and IL-12 in human blood, but lower levels of the
proinflammatory cytokines IL-1beta, IL-6, and IL-8. These results suggest that
the inflammatory and reactogenic propensities of this compound could be
considerably more favorable than other TLR8 agonists under evaluation.
PMID- 27513011
TI - Interactions of Nucleic Acid Bases with Temozolomide. Stacked, Perpendicular, and
Coplanar Heterodimers.
AB - Temozolomide (TMZ) was paired with each of the five nucleic acid bases, and the
potential energy surface searched for all minima, in the context of dispersion
corrected density functional theory and MP2 methods. Three types of arrangements
were observed, with competitive stabilities. Coplanar H-bonding structures,
reminiscent of Watson-Crick base pairs were typically the lowest in energy,
albeit by a small amount. Also very stable were perpendicular arrangements that
included one or more H-bonds. The two monomers were stacked approximately
parallel to one another in the third category, some of which contained weak and
distorted H-bonds. Dispersion was found to be a dominating attractive force,
largest for the stacked structures, and smallest for the coplanar dimers.
PMID- 27513013
TI - Efficient Pathway for Preparing Hollow Particles: Site-Specific Crosslinking of
Spherical Polymer Particles with Photoresponsive Groups That Play a Dual Role in
Shell Crosslinking and Core Shielding.
AB - Site-specific a posteriori photocrosslinking of homogeneous spherical polymer
particles and subsequent removal of the particle core-the self-templating
strategy-has been developed as an efficient pathway for hollow particle
formation. In this approach, homogeneous polymer particles containing linear
polymers bearing post-crosslinkable side-chain groups are first synthesized, and
the photoinduced crosslinking occurred only at the shell region in the
homogeneous polymer particles. Our fundamental studies clarified that the
remaining non-crosslinked photoresponsive groups in the shell region played a
crucial role in shielding the core region from photoirradiation. The shell
selective crosslinking was successfully applied to hollow polymer particle
formation by core removal. This facile route to polymeric hollow particle
formation via a self-templating strategy has great potential to be used as an
alternative because the route has high mass productivity and high simplicity as a
result of the non-use of additional sacrificial template particles and highly
toxic solvents.
PMID- 27513014
TI - Submillisecond Dynamics of Mastoparan X Insertion into Lipid Membranes.
AB - The mechanism of protein insertion into a lipid bilayer is poorly understood
because the kinetics of this process is difficult to measure. We developed a new
approach to study insertion of the antimicrobial peptide Mastoparan X into
zwitterionic lipid vesicles, using a laser-induced temperature-jump to initiate
insertion on the microsecond time scale and infrared and fluorescence
spectroscopies to follow the kinetics. Infrared probes the desolvation of the
peptide backbone and yields biphasic kinetics with relaxation lifetimes of 12 and
117 MUs, whereas fluorescence probes the intrinsic tryptophan residue located
near the N-terminus and yields a single exponential phase with a lifetime of 440
MUs. Arrhenius analysis of the temperature-dependent rates yields an activation
energy for insertion of 96 kJ/mol. These results demonstrate the complexity of
the insertion process and provide mechanistic insight into the interplay between
peptides and the lipid bilayer required for peptide transport across cellular
membranes.
PMID- 27513017
TI - Significant Improvement in Thermal and UV Resistances of UHMWPE Fabric through in
Situ Formation of Polysiloxane-TiO2 Hybrid Layers.
AB - Anatase nanocrystalline titanium dioxide coatings were produced on ultrahigh
molecular weight polyethylene (UHMWPE) fabric by radiation-induced graft
polymerization of gamma-methacryloxypropyl trimethoxysilane (MAPS) and subsequent
cohydrolysis of the graft chains (PMAPS) with tetrabutyl titanate, followed by
boiling water treatment for 180 min. The resulting material was coded as UHMWPE-g
PMAPS/TiO2 and characterized by attenuated total reflection infrared
spectrometry, differential scanning calorimetry, X-ray diffraction, thermal
gravimetry, and ultraviolet absorption spectroscopy, among others. The
predominant form of TiO2 in the thin film was anatase. The coating layer was
composed of two sublayers: an inner part consisting of an organic-inorganic
hybrid layer to prevent photocatalytic degradation of the matrix by TiO2 film,
and an outer part consisting of anatase nanocrystalline TiO2 capable of UV
absorption. This UHMWPE-g-PMAPS/TiO2 composite exhibited much better thermal
resistance than conventional UHMWPE fabric, as reflected by the higher melting
point, decreased maximum degradation rate, and higher char yield at 700 degrees
C. Compared with UHMWPE fabric, UHMWPE-g-PMAPS/TiO2 exhibited significantly
enhanced UV absorption and excellent duration of UV illumination. Specifically,
the UV absorption intensity was 2.4-fold higher than that of UHMWPE fabric; the
retention of the break strength of UHMWPE-g-PMAPS/TiO2 reached 92.3% after UV
irradiation. This work provides an approach for addressing the issue of self
degradation of TiO2-coated polymeric materials due to the inherent photoactivity
of TiO2.
PMID- 27513018
TI - Lessons from Genome Wide Association Studies.
PMID- 27513019
TI - Lessons from Genome-Wide Association Studies in Reproductive Medicine.
PMID- 27513020
TI - An Introduction to Genome-Wide Association Studies: GWAS for Dummies.
AB - Although the genetic origin of many human diseases and phenotypes has been long
and widely recognized, identification of the causative gene alleles has been
limited, slow, and cumbersome. This has changed substantially with the
introduction of genome-wide association studies (GWASs) a decade ago, fueled by
studies and reference projects of human genetic diversity and the development of
novel DNA analysis technology applicable to high-throughput and large-scale data
generation. Although GWASs essentially combine epidemiological study designs with
molecular genetic analysis techniques, it has also fundamentally changed the way
in which research was done in human genetics by the introduction of large
consortia of collaborating investigators. GWASs have over flooded many clinical
and basic research areas with gene discoveries, including those in reproductive
medicine. This review describes aspects of GWAS methodology and how this field of
human genetics is developing.
PMID- 27513021
TI - Genetics, Genome-Wide Association Studies, and Menarche.
AB - Puberty is characterized by maturation of the hypothalamic-pituitary-gonadal
axis, development of secondary sexual features, increased linear growth velocity,
maturation of the epiphyses limiting additional growth, and achievement of
menarche. The age at menarche appears to have a significant genetic component.
With the advent of genome-wide association studies (GWASs), the genome has been
interrogated to find associations between specific loci and age at menarche. It
is apparent that multiple genetic loci, epigenetic mechanisms, and environmental
factors modulate this biological event crucial for reproductive competence.
PMID- 27513022
TI - Lessons from Genome-Wide Association Studies in Reproductive Medicine: Menopause.
AB - In recent years, common genetic variants have been identified by genome-wide
association studies (GWASs) that have led to the detection of 44 genetic loci
associated with approximately 6% of common variation in age at natural menopause.
In the latest GWAS, doubling the sample size to approximately 70,000 women more
than doubled the number of signals identified, from 17 to 56. In addition, low
frequency coding variants (< 5% minor allele frequency), with relatively large
effect sizes, have been identified in two genes, by analyzing genome-wide exome
data. GWAS has been very successful in identifying novel biological pathways
involved in reproductive aging. Approximately two-thirds of the loci reported so
far include genes involved in DNA damage response (DDR), highlighting the
importance of this pathway in determining oocyte reserve. In addition, GWAS
demonstrates that the hypothalamic-pituitary axis is involved in menopause timing
as well as puberty timing, showing the first genetic link between timing of the
start and end of reproductive life. Genetic variants have been used to explore
the causal relationships between menopause timing and breast cancer. These
studies demonstrate that for a 1 year increase in menopause age, there is a 6%
increase in breast cancer risk, a value approximately double the estimate from
epidemiological studies. Prolonged exposure to estrogen during reproductive life
is the likely mechanism, rather than a direct effect of DDR variants on cancer
risk. Further work is needed to determine the mechanism for the effect of each
variant identified by GWAS and more variants will undoubtedly be discovered as
sample sizes increase, denser single nucleotide polymorphism arrays and reference
genomes are used, and populations from diverse ethnic groups are studied.
PMID- 27513023
TI - Genome-Wide Association Studies for Polycystic Ovary Syndrome.
AB - Over the past several years, the field of reproductive medicine has witnessed
great advances in genome-wide association studies (GWASs) of polycystic ovary
syndrome (PCOS), leading to identification of several promising genes involved in
hormone action, type 2 diabetes, and cell proliferation. This review summarizes
the key findings and discusses their potential implications with regard to
genetic mechanisms of PCOS. Limitations of GWAS are evaluated, emphasizing the
understanding of the reasons for variability in results between individual
studies. Root causes of misinterpretations of GWASs are also addressed. Finally,
the impact of GWAS on future directions of multi- and interdisciplinary studies
is discussed.
PMID- 27513024
TI - Primary Ovarian Insufficiency.
AB - Primary ovarian insufficiency (POI), also known as premature ovarian failure or
premature menopause, is defined as cessation of menstruation before the expected
age of menopause. Potential etiologies for POI can be divided into genetic,
autoimmune, and iatrogenic categories. This review will try to summarize the
genetic basis of POI focusing on recent data that are available using newer
genetic techniques such as genome-wide association studies, whole-exome
sequencing (WES), or next-generation sequencing techniques. By using these
techniques, many genes have arisen that play some role in the pathophysiology of
POI. Some of them have been replicated in other studies; however, the majority
has not been proven yet to be unequivocally causative through functional
validation studies. Elucidating the genetic and molecular basis of POI is of
paramount importance not only in understanding ovarian physiology but also in
providing genetic counseling and fertility guidance. Once additional variants are
detected, it might become possible to predict the age of (premature) menopause in
women at risk for POI. Women having certain perturbations of POI can be offered
the option of oocyte cryopreservation, with later thawing and use in assisted
reproductive technology at an appropriate age.
PMID- 27513025
TI - Genetic Association Studies in Uterine Fibroids: Risk Alleles Presage the Path to
Personalized Therapies.
AB - Uterine leiomyoma (UL) is the most common tumor of the female reproductive
system. Epidemiological analyses, including familial aggregation, twin studies,
and racial discrepancies in disease prevalence and morbidity, indicated genetic
factors influence risk for developing UL. Genome-wide association studies (GWASs)
are a powerful method for identifying genetic variants that are associated with
elevated risk for a common, complex disease. To date, three genome-wide scans for
UL have been performed: a GWAS in Japanese women, a genome-wide linkage and
association study in women of European decent, and an admixture-based analysis in
African American women. Results from each of the three genome-wide scans
performed have had varying success in identifying unique loci associated with
predisposition to developing UL. Here, we address the evidence for a genetic
basis for UL risk, discuss genetic association studies and their results, and
identify challenges and future directions for UL GWAS analyses.
PMID- 27513027
TI - Benefit of TeamSTEPPS Rounding Improvement Project on Infection-Related
Monitoring.
AB - BACKGROUND: Team Strategies and Tools to Enhance Performance and Patient Safety
(TeamSTEPPS) was developed to improve teamwork and patient safety. It was shown
to benefit patient care in complex clinical settings including intensive care
units (ICUs). Our two trauma/surgical ICUs received TeamSTEPPS training, but only
Unit 1 participated in a TeamSTEPPS Rounding Improvement Project (TRIP). Our goal
was to assess any unintended benefit to infection-related monitoring and
prevention from TRIP. We hypothesized that TRIP implementation in ICUs would be
associated with increased monitoring, resulting in improved antibiotic and
invasive catheter/tube stewardship. METHODS: From September through November
2014, observers prospectively collected data on rounds in both units. Unit
personnel were blinded to the data collection process. Monitoring parameters
obtained for each patient encounter included review of invasive catheter/tube
presence and review of antibiotic indication and course. For patients who
received antibiotic and had invasive catheter/tube, we conducted a retrospective
review for treatment parameters such as antibiotic duration and adherence to
treatment plan, inappropriate antibiotics duration, and invasive catheter/tube
duration. RESULTS: A total of 416 patient encounters were observed. The use of
invasive catheter/tube was reviewed on rounds substantially more in Unit 1 than
Unit 2 (83% vs. 51%, p < 0.005). In the 135 encounters with patients on
antibiotic, review of antibiotic indication, stop date, day into course, and all
three components occurred substantially more in Unit 1. On the basis of the 65
different antibiotic courses encompassed by the 135 encounters, antibiotic
duration, adherence to antibiotic treatment plan, and inappropriate antibiotic
days were not substantially different between the units. From the same 135
encounters, 125 encounters also had invasive catheter/tube placement.
Substantially more discussion of catheter/tube presence occurred in Unit 1, but
the duration of its presence was not substantially different. CONCLUSION: The
TeamSTEPPS Rounding Improvement Project was associated with an unintended,
increased discussion and monitoring of antibiotic and invasive catheter/tube
usage. However, this did not translate into substantial immediate treatment
differences.
PMID- 27513028
TI - Synthesis and Properties of Sila[n]helicenes via Dehydrogenative Silylation of C
H Bonds under Rhodium Catalysis.
AB - Use of a rhodium catalyst with (R)-(S)-BPPFA ligand allows efficient synthesis of
sila[n]helicenes via dehydrogenative silylation of C-H bonds. By selecting the
proper ligands, the current method provides the ability to prepare unsymmetrical
sila[n]helicene derivatives without any oxidants. The resulting sila[6]helicene
is a rare example of a five-membered ring-fused [6]helicene, which was isolated
as a single pure enantiomer without substituents on the terminal benzene rings.
PMID- 27513026
TI - Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to
the Patient.
AB - Endometriosis is a heritable, complex chronic inflammatory disease, for which
much of the causal pathogenic mechanism remains unknown. Genome-wide association
studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10
independent genetic loci associated with endometriosis. Most of these were more
strongly associated with revised American Fertility Society stage III/IV, rather
than stage I/II. The loci are almost all located in intergenic regions that are
known to play a role in the regulation of expression of target genes yet to be
identified. To identify the target genes and pathways perturbed by the implicated
variants, studies are required involving functional genomic annotation of the
surrounding chromosomal regions, in terms of transcription factor binding,
epigenetic modification (e.g., DNA methylation and histone modification) sites,
as well as their correlation with RNA transcription. These studies need to be
conducted in tissue types relevant to endometriosis-in particular, endometrium.
In addition, to allow biologically and clinically relevant interpretation of
molecular profiling data, they need to be combined and correlated with detailed,
systematically collected phenotypic information (surgical and clinical). The WERF
Endometriosis Phenome and Biobanking Harmonisation Project is a global
standardization initiative that has produced consensus data and sample collection
protocols for endometriosis research. These now pave the way for collaborative
studies integrating phenomic with genomic data, to identify informative subtypes
of endometriosis that will enhance understanding of the pathogenic mechanisms of
the disease and discovery of novel, targeted treatments.
PMID- 27513029
TI - Influence of skeletal class in the morphology of cervical vertebrae: A study
using cone beam computed tomography.
AB - OBJECTIVES: To quantify the prevalence of cervical vertebrae anomalies and to
analyze any association between them and skeletal malocclusions or head posture
positions in the same study. MATERIALS AND METHODS: Two hundred forty patients
who were attending the Department of Orthodontics of the University of Valencia
for orthodontic treatment were selected and divided into three groups: skeletal
Class I (control group, 0 degrees = 4 degrees
), and Class III (ANB <= 0 degrees ) according to ANB Steiner angle. The
morphology of the first five cervical vertebrae was analyzed with cone beam
computed tomography to identify any anomalies. Intra- and interobserver error
methods were calculated. RESULTS: Dehiscence and fusion of one unit (both 23.3%)
and partial cleft (11.7%) were the most frequent anomalies, while
occipitalization was the least common (3.3%). Dehiscence anomaly was observed
when the control group was compared with Classes II and III and partial cleft
anomaly when Class I was compared with Class III. Furthermore, NSBa and ss-N
sm/ANB angles were associated with partial cleft anomaly, while NSL/NL angle and
extended head posture were associated with fusion anomaly. CONCLUSIONS: Fusion,
dehiscence, and partial cleft were the most frequent cervical vertebrae
anomalies. Dehiscence and partial cleft were found to present statistically
significant differences between Class I and Classes II and III. Cervical
vertebrae anomalies and head posture were associated with fusion.
PMID- 27513030
TI - Modern trends in Class III orthognathic treatment: A time series analysis.
AB - OBJECTIVE: To examine the current trends in surgical-orthodontic treatment for
patients with Class III malocclusion using time-series analysis. MATERIALS AND
METHODS: The records of 2994 consecutive patients who underwent orthognathic
surgery from January 1, 2004, through December 31, 2015, at Seoul National
University Dental Hospital, Seoul, Korea, were reviewed. Clinical data from each
surgical and orthodontic treatment record included patient's sex, age at the time
of surgery, malocclusion classification, type of orthognathic surgical procedure,
place where the orthodontic treatment was performed, orthodontic treatment
modality, and time elapsed for pre- and postoperative orthodontic treatment.
RESULTS: Out of the orthognathic surgery patients, 86% had Class III
malocclusion. Among them, two-jaw surgeries have become by far the most common
orthognathic surgical treatment these days. The age at the time of surgery and
the number of new patients had seasonal variations, which demonstrated opposing
patterns. There was neither positive nor negative correlation between pre- and
postoperative orthodontic treatment time. Elapsed orthodontic treatment time for
both before and after Class III orthognathic surgeries has been decreasing over
the years. CONCLUSION: Results of the time series analysis might provide
clinicians with some insights into current surgical and orthodontic management.
PMID- 27513031
TI - Eyes on New Product Development.
PMID- 27513068
TI - High dielectric permittivity and improved mechanical and thermal properties of
poly(vinylidene fluoride) composites with low carbon nanotube content: effect of
composite processing on phase behavior and dielectric properties.
AB - The composite processing technique and nanofiller concentration and its
functionalization significantly alter the properties of polymer nanocomposites.
To realize this, multi-walled carbon nanotubes (CNT) were dispersed in a
poly(vinylidene fluoride) (PVDF) matrix at carefully selected CNT concentrations
by two illustrious methods, such as solution-cast and melt-mixing.
Notwithstanding the processing method, CNTs induced predominantly the gamma-phase
in PVDF, instead of the commonly obtained beta-phase upon nanofiller
incorporation, and imparted significant improvements in dielectric properties.
Acid-treatment of CNT improved its dispersion and interfacial adhesion
significantly with PVDF, and induced a higher gamma-phase content and better
dielectric properties in PVDF as compared to pristine CNT. Further, the gamma
phase content was found to be higher in solution-cast composites than that in
melt-mixed counterparts, most likely due to solvent-induced crystallization in a
controlled environment and slow solvent evaporation in the former case. However,
interestingly, the melt-mixed composites showed a significantly higher dielectric
constant at the onset of the CNT networked-structure as compared to the solution
cast composites. This suggests the possible role of CNT breakage during melt
mixing, which might lead to higher space-charge polarization at the polymer-CNT
interface, and in turn an increased number of pseudo-microcapacitors in these
composites than the solution-cast counterparts. Notably, PVDF with 0.13 vol%
(volume fraction, f c = 0.0013) of acid-treated CNTs, prepared by melt-mixing,
displayed the relative permittivity of ~217 and capacitance of ~5430 pF, loss
tangent of ~0.4 at 1 kHz and an unprecedented figure of merit of ~10(5). We
suggest a simple hypothesis for the gamma-phase formation and evolution of the
high dielectric constant in these composites. Further, the high-dielectric
composite film showed marked improvements in mechanical and thermal properties
over the neat PVDF film. These composites with exceptional dielectric properties
and concomitant improvement in mechanical and thermal properties offer a great
promise for use in flexible and mechanically robust charge storage devices.
PMID- 27513069
TI - Fucoidan reduces oxidative stress by regulating the gene expression of HO-1 and
SOD-1 through the Nrf2/ERK signaling pathway in HaCaT cells.
AB - Fucoidan, a sulfated polysaccharide, is found in edible brown algae. In the
present study, the molecular mechanisms of fucoidan against mild oxidative stress
in human keratinocytes were investigated. The current study indicated that
fucoidan significantly augmented the antioxidants heme oxygenase-1 (HO-1) and
superoxide dismutase-1 (SOD-1) via the upregulation of nuclear factor erythroid 2
related factor 2 (Nrf2) and markedly reduced the cytoplasmic stability of kelch
like ECH-associated protein 1. The upregulation of HO-1 and SOD-1 detected in the
fucoidan-treated cells may be responsible for the increased resistance to mild
oxidative stress, indicating that fucoidan may augment the activities of
antioxidant enzymes via stimulating Nrf2. This is the first report, to the best
of our knowledge, to demonstrate that fucoidan attenuates oxidative stress by
regulating the gene expression of SOD-1 and HO-1 via the Nrf2/extracellular
signal-regulated kinase signaling pathway.
PMID- 27513070
TI - Cardiovascular Health Status by Occupational Group - 21 States, 2013.
AB - Cardiovascular disease (CVD) accounts for one of every three deaths in the United
States, making it the leading cause of mortality in the country (1). The American
Heart Association established seven ideal cardiovascular health behaviors or
modifiable factors to improve CVD outcomes in the United States. These
cardiovascular health metrics (CHMs) are 1) not smoking, 2) being physically
active, 3) having normal blood pressure, 4) having normal blood glucose, 5) being
of normal weight, 6) having normal cholesterol levels, and 7) eating a healthy
diet (2). Meeting six or all seven CHMs is associated with a lower risk for all
cause, CVD, and ischemic heart disease mortalities compared with the risk to
persons who meet none or only one CHM (3). Fewer than 2% of U.S. adults meet all
seven of the American Heart Association's CHMs (4). Cardiovascular morbidity and
mortality account for an estimated annual $120 billion in lost productivity in
the workplace; thus, workplaces are viable settings for effective health
promotion programs (5). With over 130 million employed persons in the United
States, accounting for about 55% of all U.S. adults, the working population is an
important demographic group to evaluate with regard to cardiovascular health
status. To determine if an association between occupation and CHM score exists,
CDC analyzed data from the 2013 Behavioral Risk Factor Surveillance System
(BRFSS) industry and occupation module, which was implemented in 21 states. Among
all occupational groups, community and social services employees (14.6%),
transportation and material moving employees (14.3%), and architecture and
engineering employees (11.6%) had the highest adjusted prevalence of meeting two
or fewer CHMs. Transportation and material moving employees also had the highest
prevalence of "not ideal" ("0" [i.e., no CHMs met]) scores for three of the seven
CHMs: physical activity (54.1%), blood pressure (31.9%), and weight (body mass
index [BMI]; 75.5%). Disparities in cardiovascular health status exist among U.S.
occupational groups, making occupation an important consideration in employer
sponsored health promotion activities and allocation of prevention resources.
PMID- 27513071
TI - Isolated (hypoxic) hepatic perfusion with high-dose chemotherapy in patients with
unresectable liver metastases of uveal melanoma: results from two experienced
centres.
AB - Uveal melanoma patients have a poor survival after the diagnosis of metastatic
disease. Isolated hepatic perfusion (IHP) was developed to treat patients with
unresectable metastases confined to the liver. This retrospective analysis
focuses on treatment characteristics, complications, toxicity and survival after
IHP. Patients with uveal melanoma metastases confined to the liver treated with
IHP in two experienced hepato-pancreatic-biliary surgery centres (Erasmus MC
Cancer Institute and Leiden University Medical Center) were included. Between
March 1999 and April 2009, 30 patients were treated with IHP. The duration of
surgery was 3.7 h (Erasmus MC Cancer Institute) versus 8.7 h (Leiden University
Medical Center) and also the dosage of melphalan differed: 1 mg/kg body weight
(n=12) versus a dose of 170-200 mg (n=18) or melphalan (100 mg) combined with
oxaliplatin (50 or 100 mg) (n=3). The length of hospital stay was 10 days. Two
patients developed occlusion of the hepatic artery and died, respectively, 3 days
and 1.5 months after surgery. Progression-free survival was 6 (1-16) months and
recurrences occurred mainly in the liver. The median overall survival was 10 (3
50) months. IHP is a potentially beneficial treatment modality resulting in a
reasonable overall survival for uveal melanoma patients. Because of considerable
morbidity related to the open procedure, a percutaneous system has been developed
and is currently being investigated.
PMID- 27513072
TI - CE: Original Research: Predicting Injurious Falls in the Hospital Setting:
Implications for Practice.
AB - : BACKGROUND: Despite years of research and increasingly evidence-based practice,
falls continue to be the most commonly reported adverse events experienced by
hospitalized adults. Yet a majority of the relevant research has focused on
predicting and preventing falls in general; there has been little focus on
injurious falls. PURPOSE: The purpose of this retrospective study was to
determine which patient factors are associated with injurious falls in
hospitalized adults. METHODS: The study site's adverse event reporting database
was used to identify 1,369 patients who fell between January 1, 2006, and October
31, 2013. Of these, 381 (27.8%) subjects suffered injurious falls. Variables of
interest included age, sex, fall history, use of diuretics, use of central
nervous system medications, cognitive impairment, primary discharge diagnoses,
abnormal laboratory values, impaired mobility, and body mass index. FINDINGS:
Bivariate analysis revealed a statistically significant association between
injurious falls and having a primary discharge diagnosis of "symptoms, signs, and
ill-defined conditions." Having this discharge diagnosis was a significant
predictor of injurious falls. CONCLUSIONS: Findings from this study may help
hospital clinicians to better identify which patients are most at risk for
injurious falls and to create better fall-related injury prevention
interventions.
PMID- 27513073
TI - CE: Military Sexual Trauma in Male Service Members.
AB - : The experience of military sexual trauma (MST), which can result from assault,
battery, or harassment of a sexual nature, may jeopardize the mental health of
service members as well as that of their family members, colleagues, and
community members. Although a greater proportion of female than male service
members are subjected to MST, the Department of Defense estimates that the
absolute numbers of affected men and women, across all ranks and branches of
military service, are nearly equal because roughly 85% of military members are
men. Little research has explored the effects of MST on men. This article
discusses the unique ways in which men may experience MST, and examines how
social stereotypes of masculinity, myths surrounding sexual assault, and military
culture and structure often influence a man's interpretation of an attack and his
likelihood of reporting the incident or seeking treatment. It describes current
treatments for MST-related mental health conditions and addresses implications
for nurses and other health care professionals.
PMID- 27513074
TI - Assessment of CK17 as a Marker for the Diagnosis of Differentiated Vulvar
Intraepithelial Neoplasia.
AB - Differentiated vulvar intraepithelial neoplasia (dVIN), precursor of vulvar
squamous cell carcinoma, is human papilloma virus independent and often found in
a background of lichen sclerosus (LS) and lichen simplex chronicus (LSC). Subtle
histologic findings make the diagnosis of dVIN difficult, and, although the use
of p53 and Ki-67 has been of some value, there is a need for a better
immunohistochemical marker. Cytokeratin 17 (CK17), a cytoskeletal intermediate
filament protein, has previously been used in the diagnosis of anogenital
lesions. Here we evaluated CK17 in dVIN in comparison with LS, LSC, and usual VIN
(uVIN/HSIL). Twenty-nine cases of dVIN, 9 cases of uVIN, 8 cases of LS, and 7 of
LSC were evaluated using CK17, Ki-67, and p53. All 29 dVIN cases displayed
immunoreactivity for CK17, with 27 (93%) showing intermediate to strong and
diffuse reactivity. No cases of uVIN displayed diffuse CK17 expression, whereas
63% of LS and 29% of LSC displayed intermediate to strong diffuse
immunoreactivity, confined to the upper half of the epithelium. P53 and Ki-67
expression was present in varying degrees in all types of lesions, displaying
limited discriminatory power for dVIN. Our findings suggest that CK17, although
not specific for dVIN, when combined with histologic findings, Ki-67, and p53
immunohistochemistry, can be a marker of vulvar dysplasia and serve as an adjunct
in the diagnosis of dVIN. Specifically, in small biopsies, the presence of
diffuse suprabasal or full thickness expression strongly favors a diagnosis of
dVIN over LSC, whereas focal and/or superficial expression supports a diagnosis
of LSC.
PMID- 27513075
TI - Collision Signet-Ring Stromal Tumor and Steroid Cell Tumor of the Ovary: Report
of the First Case.
AB - To date, the vast majority of collision tumors in the ovary include either a
teratoma, sex cord-stromal tumor, or both. Here we report the first case of a
collision tumor consisting of a steroid cell tumor and a signet-ring stromal
tumor.
PMID- 27513076
TI - Metastatic Ovarian Tumors Originating From a Small Bowel Adenocarcinoma - A Case
Report and Brief Literature Review.
AB - Approximately 1.6% of tumors metastatic to the ovary of nongynecologic origin are
from a small bowel adenocarcinoma (SBA). However, the incidence of SBA is
extremely rare (0.23 cases/100,000 people), which suggests a high frequency of
ovarian metastasis, although the reason is unknown. To identify the
characteristics of ovarian tumor metastasis from SBA, we reviewed 72 cases
reported in the English literature, including the case presented in this report.
The mean age of the patients was 46.7 yr. Solitary ovarian metastasis was
observed in 67% of the cases, and ovarian metastasis was accompanied by
peritoneal dissemination in 33% of the cases. Although duodenal adenocarcinoma
has the highest incidence among the SBAs, jejunal adenocarcinoma, particularly
that at the proximal end, is the type of SBA that most frequently metastasizes to
the ovary. Among the cases of ovarian metastasis from SBA, 51% were bilateral,
33% were unilateral to the right ovary, and 16% were unilateral to the left
ovary.
PMID- 27513077
TI - Mucinous Differentiation With Tumor Infiltrating Lymphocytes Is a Feature of
Sporadically Methylated Endometrial Carcinomas.
AB - Defects in the DNA mismatch-repair system are identified in ~25%-30% of
endometrial carcinomas (ECs). Whereas some ECs are due to germline Lynch syndrome
(LS)-associated mutations, the majority demonstrate sporadic MLH1 promoter
hypermethylation (MLH1hm). MLH1hm characterizes a unique subset of colorectal
cancers with a relatively poor prognosis; however, the morphology and behavior of
sporadically methylated ECs (SMECs) are less well understood. We herein review
the clinicopathologic features of 34 SMECs diagnosed at The University of
Virginia and compare them with LS-associated and Lynch-like endometrial cancers.
Most SMECs were centered in the uterine fundus (74%) and displayed Grade 1 (35%)
or Grade 2 (41%) endometrioid morphology. Mucinous differentiation was present in
50%, and 65% showed tumor-infiltrating lymphocytes. Cases with undifferentiated
components or sarcomatous differentiation were relatively rare (9%). Most SMECs
presented at stage 1 or 2 (91%). When compared with LS and Lynch-like endometrial
cancers, SMECs occurred ~8 yr later and were significantly more likely to show
conventional endometrioid morphology (P=0.04), mucinous differentiation
(P=0.002), and tumor-infiltrating lymphocytes (P=0.002). These findings suggest
that SMECs constitute a clinicopathologically distinct subset of mismatch-repair
deficient/high-level microsatellite instability tumors. Future studies are needed
to further understand the implications of MLH1hm on the prognosis and treatment
of endometrial cancer.
PMID- 27513078
TI - Extrauterine Placental Site Trophoblastic Tumor Involving the Vagina.
AB - Very few cases of placental site trophoblastic tumor (PSTT) primarily involving
extrauterine sites have been reported to date. We report a case of a 29-year-old
female who presented with a vaginal nodule 9 months after delivery at an outside
hospital which was initially diagnosed as a poorly differentiated squamous cell
carcinoma. Subsequently she was referred to our institute, and on the basis of
histology, mildly elevated serum beta-HCG level, and immunohistochemistry, PSTT
was diagnosed. After the completion of chemotherapy, the vaginal nodule
completely regressed and serum beta-hCG returned to baseline. Her follow-up has
been unremarkable. This case highlights the importance of the fact that PSTT can
be easily misdiagnosed at extrauterine sites in the absence of proper clinical,
histologic, and immunohistochemical correlation.
PMID- 27513079
TI - Thin HSIL of the Cervix: Detecting a Variant of High-grade Squamous
Intraepithelial Lesions With a p16INK4a Antibody.
AB - The WHO defines thin high-grade squamous intraepithelial lesions (HSIL) as a high
grade intraepithelial lesion of the cervix that is usually <=9 cells thick. These
lesions usually develop in early metaplastic squamous epithelium without
anteceding low-grade squamous intraepithelial lesions (LSIL). The prevalence of
thin HSIL is not well documented. We evaluated different characteristics of thin
HSIL at time of treatment. We studied 25 formalin-fixed and paraffin-embedded
conization specimens processed as step-serial sections. HSIL<=9 cells thick were
classified as thin HSIL. HSIL>=10 cells thick were classified as classic HSIL.
Immunohistochemical p16 staining was used to confirm lesions of thin HSIL.
Overall, 19 (76%) specimens contained both thin HSIL and classic HSIL, 4 (16%)
contained thin HSIL only, 1 (4%) contained classic-type HSIL only, and 1 (4%)
contained thin HSIL and LSIL. Thin HSILs developed in both the columnar surface
epithelium and deep cervical glandular epithelium. Most thin HSILs were 5 cells
thick. All HSILs (thin and classic) were located inside the transformation zone
and had a median horizontal extension of 8 mm (range, 0.3 to 21 mm). Our findings
suggest that thin HSILs are frequent findings, that they coexist with classic
HSIL, and preferably arise in the exposed parts of the transformation zone
including the glandular crypts.
PMID- 27513080
TI - The Added Value of Pathology Review in Vulvar Cancer: Results From a Population
based Cohort Study.
AB - We conducted a population-based patterns of care study of vulvar carcinoma. This
paper describes the changes in reporting based on pathology review. This is a
retrospective population-based cohort study. We obtained all pathology records
available from the provincial cancer registry for primary invasive squamous cell
carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were
conducted centrally by a group of gynecologic pathologists and were identified
during abstraction. Corresponding original reports were matched to pathology
review reports based on accession numbers. We compared the reported value for
presence/absence of invasion, grade, depth, thickness, size, lymphovascular space
invasion, peripheral margin status, and deep margin status in the original and
review report. A total of 1011 vulvar resection reports were identified. From
these, we identified 316 pairs of original/review reports. Missing data were
common but improved in the reviews. In total, 55 (17%) reports had at least 1
change from the original to the review based on presence of invasion, depth,
lymphovascular space invasion, or margin. When we included reports where a
variable was missing in the original but then completed in the review, there were
clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare
diagnosis and pathology reviews resulted in potentially important clinical
changes in a significant proportion of cases. Referral pathologists play an
important role in contributing to high-quality clinical decisions.
PMID- 27513081
TI - Lipomatous Angiomyofibroblastoma of the Vulva: Report of a Rare Variant.
AB - Angiomyofibroblastoma is a rare and benign tumor that usually involves
vulvovaginal area in women of reproductive age and early menopause. We report a
lipomatous angiomyofibroblastoma in a 55-year-old multigravid woman. This tumor
measured 9 cm in size and contained prominent mature adipose tissue that
comprised approximately 50% of the tumor.
PMID- 27513082
TI - The AMPK Activator Aicar Ameliorates Age-Dependent Myocardial Injury in Murine
Hemorrhagic Shock.
AB - The development of myocardial dysfunction in patients with hemorrhagic shock is
significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is
a pivotal orchestrator of energy homeostasis, which coordinates metabolic
recovery after cellular stress. We investigated whether AMPK-regulated pathways
are age-dependent in hemorrhage-induced myocardial injury and whether AMPK
activation by 5-amino-4-imidazolecarboxamide riboside (AICAR) affords
cardioprotective effects. Anesthetized C57/BL6 young (3-5 months old) and mature
(9-12 months old) male mice were subjected to hemorrhagic shock by blood
withdrawing followed by resuscitation with shed blood and Lactated Ringer's
solution. Mice were sacrificed at 3 h after resuscitation, and plasma and hearts
were harvested for biochemical assays. Vehicle-treated mature mice exhibited
higher myocardial injury and higher levels of plasma biomarkers of cardiovascular
injury (endocan and follistatin) when compared with young mice. Cardiac cell
mitochondrial structure was also markedly impaired in vehicle-treated mature mice
when compared with young mice. At molecular analysis, an increase of the
phosphorylated catalytic subunit pAMPKalpha was associated with nuclear
translocation of the peroxisome proliferator-activated receptor gamma coactivator
alpha in young, but not mature mice. No changes in autophagy were observed as
evaluated by the conversion of the light-chain (LC)3B-I protein to LC3B-II form.
Treatment with AICAR ameliorated myocardial damage in both age groups. However,
AICAR therapeutic effects were less effective in mature mice than young mice and
involved distinct mechanisms of action. Thus, our data demonstrate that during
hemorrhagic shock AMPK-dependent metabolic mechanisms are important for
mitigating myocardial injury. However, these mechanisms are less competent with
age.
PMID- 27513083
TI - Circulatory Failure During Noninhaled Forms of Cyanide Intoxication.
AB - Our objective was to determine how circulatory failure develops following
systemic administration of potassium cyanide (KCN). We used a noninhaled modality
of intoxication, wherein the change in breathing pattern would not influence the
diffusion of CN into the blood, akin to the effects of ingesting toxic levels of
CN. In a group of 300 to 400 g rats, CN-induced coma (CN i.p., 7 mg/kg) produced
a central apnea within 2 to 3 min along with a potent and prolonged gasping
pattern leading to autoresuscitation in 38% of the animals. Motor deficits and
neuronal necrosis were nevertheless observed in the surviving animals. To clarify
the mechanisms leading to potential autoresuscitation versus asystole, 12
urethane-anesthetized rats were then exposed to the lowest possible levels of CN
exposure that would lead to breathing depression within 7 to 8 min; this dose
averaged 0.375 mg/kg/min i.v. At this level of intoxication, a cardiac depression
developed several minutes only after the onset of the apnea, leading to cardiac
asystole as PaO2 reached value approximately 15 Torr, unless breathing was
maintained by mechanical ventilation or through spontaneous gasping. Higher
levels of KCN exposure in 10 animals provoked a primary cardiac depression, which
led to a rapid cardiac arrest by pulseless electrical activity (PEA) despite the
maintenance of PaO2 by mechanical ventilation. These effects were totally
unrelated to the potassium contained in KCN. It is concluded that circulatory
failure can develop as a direct consequence of CN-induced apnea but in a narrow
range of exposure. In this "low" range, maintaining pulmonary gas exchange after
exposure, through mechanical ventilation (or spontaneous gasping), can reverse
cardiac depression and restore spontaneous breathing. At higher level of
intoxication, cardiac depression is to be treated as a specific and spontaneously
irreversible consequence of CN exposure, leading to a PEA.
PMID- 27513084
TI - Simvastatin Attenuates Acute Lung Injury via Regulating CDC42-PAK4 and
Endothelial Microparticles.
AB - BACKGROUND: Simvastatin has lung vascular-protective effects via augmentation of
endothelial barrier function. Accordingly, on the basis of our previous study, we
hypothesized that endothelial cell (EC) protection by simvastatin is dependent on
the stabilization on cytoskeletons. METHODS: Sixty C57BL/6 mice were divided into
two experimental groups: lipopolysaccharide (LPS) group (L group) and
LPS+simvastatin treated group (L+S group). All mice in these two groups received
an intraperitoneal injection of LPS (10 mg/kg/d). Simvastatin was administered
intraperitoneally immediately after the LPS injection in animals of the L+S group
at a dose of 20 mg/kg/day. Lung injury degree and the protective effects of
simvastatin against LPS-induced lung injury were assessed at the time-points of
24, 48, and 72 h postinjection. Serum alanine transaminase (ALT), serum
creatinine (Scr) were identified to assess the hepatic and renal side-effects of
simvastatin. RESULTS: LPS inhibited the cytoskeletal regulating proteins of Cdc42
and PAK4, and was accompanied by an increased circulating endothelial
microparticles (EMPs) level. The adherent junction (AJ) protein of VE-cadherin
was also decreased by LPS, and was accompanied by a thickening alveolar wall,
increased lung W/D values, and high albumin concentration in bronchoalveolar
lavage. Protective effects of simvastatin against LPS-induced lung injury were
illustrated by regulating and stabilizing cytoskeletons, as well as intercellular
AJs. The values of ALT and Scr were all lower than the common upper limits
according to assay kits. CONCLUSION: An increased serous EMP level associated
with Cdc42-PAK4 can be deemed as a useful pulmonary injury marker in LPS-treated
mice, and our results might be more relevant in guiding the clinical treatment of
ALI by intervening Cdc42-PAK4 or EMPs.
PMID- 27513085
TI - Novel Approach in Monocyte Intracellular TNF Measurement: Application to Sepsis
Induced Immune Alterations.
AB - OBJECTIVE: The monitoring of septic shock induced immunosuppression has been
proposed to identify patients who could benefit from specific immunoadjuvant
therapies. Among potential biomarkers to monitor immunological status, functional
testing remains the gold standard because it directly measures the capacity of a
cell population to respond to an immune challenge. We investigated a new approach
in intracellular staining for flow cytometry to measure tumor necrosis factor
(iTNF) produced in vitro by monocytes in response to lipopolysaccharide. DESIGN,
SETTING, SUBJECTS, AND INTERVENTIONS: Observational study in intensive care unit
and immunology laboratory of a university medical center. Sixteen septic shock
patients and eight control subjects were included. MAIN RESULTS: Monocyte iTNF
was determined by flow cytometry in whole blood and completed in 2.5 h according
to a no-wash, no centrifuge procedure. Lipopolysaccharide challenge induced a
tremendous expression of iTNF that was statistically more pronounced in controls
than in patients. This was observed when results were expressed as medians of
fluorescence intensity (median: 16.1 [IQR: 14.5-19.1] vs. 5 [4.0-8.0], P =
0.0001) or as percentages of positive cells (99.7 [99.6-99.8] vs. 85 [74-97], P =
0.0001). iTNF expression was correlated to monocyte HLA-DR expression in patients
and controls. CONCLUSIONS: These preliminary results illustrate the feasibility
of immune functional testing on a routine manner in septic shock patients. They
now deserve to be widely assessed and validated in various intensive care unit
conditions. This could be a major step to characterize the rapidly changing
immune response overtime and thus permit personalized medicine.
PMID- 27513087
TI - Selective Unidirectional Horizontal Saccadic Paralysis From Acute Ipsilateral
Pontine Stroke.
AB - BACKGROUND: Impairment of unidirectional horizontal saccades with sparing of
smooth pursuit has been described in human lesions in the dorsomedial pons. They
have been too large to allow localization to the pontine paramedian reticular
formation (PPRF). METHODS: Single case report. RESULTS: A patient with impaired
rightward saccades but spared rightward pursuit eye movements had a brain MRI
showing a discrete area of restricted diffusion in the region corresponding to
the PPRF. CONCLUSIONS: This case provides support for the concept that PPRF
lesions in humans may selectively impair unidirectional horizontal saccades.
PMID- 27513088
TI - A dismantling study of the Partners for Change Outcome Management System.
AB - The current study used a dismantling design to investigate the relative efficacy
of components of the Partners for Change Outcome Management System (PCOMS;
Duncan, 2012). Clients (n = 94) from a university counseling center were randomly
assigned to 1 of 3 conditions: PCOMS Full, Outcome Rating Scale (ORS)-only, or
Session Rating Scale (SRS)-only and nested within therapists (n = 12). Results
from hierarchical linear modeling and a 2-way analysis of variance indicated no
statistically significant differences in outcome or rate of change on the
Behavior Symptom Checklist-18 (BSI-18; Derogatis, 2001) across all 3 conditions.
These findings suggest that using either the ORS or SRS component of the PCOMS
may yield equivalent outcomes to that of the full PCOMS. Additional dismantling
studies with various populations and settings are needed to further clarify the
relative influence of the ORS, SRS, and full PCOMS on client outcomes. (PsycINFO
Database Record
PMID- 27513089
TI - Scope and Limitations of Typical Copper-Free Bioorthogonal Reactions with DNA:
Reactive 2'-Deoxyuridine Triphosphates for Postsynthetic Labeling.
AB - Four triphosphates of 2'-deoxyuridine that carried the following bioorthogonally
reactive groups were synthesized by organic-chemical methods. Two triphosphates
with tetrazines and one with a cyclopropene moiety were designed for Diels-Alder
reactions with inverse electron demand, and one triphosphate with a tetrazole
core was designed for the "photoclick" cycloaddition. These triphosphates were
not only successfully applied for oligonucleotide preparation by standard DNA
polymerases, including Hemo KlenTaq, Vent, and Deep Vent, but also bypassed for
full length primer extension products. Fluorescent labeling of the primer
extension products was achieved by fluorophores with reactive counterparts and
analyzed by polyacrylamide gel electrophoresis mobility shifts. The tetrazine
oligonucleotide conjugates were reacted with carboxymethylmonobenzocyclooctyne-
and bicyclononyne-modified fluorophores. The yield of these postsynthetic
reactions could significantly be improved by a more stable but still reactive
nicotinic acid-derived tetrazine and by changing the key experimental conditions,
mainly the pH of 7.2 and the temperature of 45-55 degrees C. The cyclopropene
oligonucleotide conjugate could be successfully labeled with a tetrazine-modified
rhodamine in very good yields. The "photoclick" cycloaddition between tetrazole
oligonucleotide conjugates and a maleimide-modified dye worked quantitatively.
The combination of primer extension, bypass, and bioorthogonal modification works
also for double and triple labeling using the cyclopropene-modified 2'
deoxyuridine triphosphate.
PMID- 27513091
TI - Sulfonyl-Substituted Heteroleptic Cyclometalated Iridium(III) Complexes as Blue
Emitters for Solution-Processable Phosphorescent Organic Light-Emitting Diodes.
PMID- 27513092
TI - Structural Diversity of Cadmium(II) Coordination Polymers Induced by Tuning the
Coordination Sites of Isomeric Ligands.
AB - When the coordination sites of ligands were shifted, the solvothermal reactions
of four positional isomeric asymmetrical pyridyldicarboxylatic acids with
Cd(NO3)2 generated four new coordination polymers, [Cd(L1)(DMF)3].DMF.H2O (1),
[H2N(CH3)2]2[Cd(L2)2].3DMF.H2O (2), [Cd(L3)(H2O)2] (3), and [Cd(L4)].1.5DMF (4),
where DMF = N,N-dimethylformamide, H2L1 = 2-(3'-carboxylphenyl)isonicotinic acid,
H2L2 = 2-(4'-carboxylphenyl)isonicotinic acid, H2L3 = 5-(3'
carboxylphenyl)nicotic acid, and H2L4 = 2-(3'-pyridyl)terephthalic acid. 1 shows
a rare 2D fabric structure. 2 discloses a grid-layer structure with heterochiral
helical chains and in which three sets of layers stack in different directions,
affording an unprecedented 2D + 2D + 2D -> 3D polycatenating framework with 3D
intersecting porous systems. 3 also displays a 2D layer possessing strong
intralayer pi...pi interactions and interlayer hydrogen bonds. 4 contains a rare
Cd2(COO)4 paddle-wheel unit and forms a 3D framework with 1D open channels. The
carboxyl and pyridyl groups of the positional isomeric H2L1-H2L4 ligands show
distinct bridging fashions, which leads to the production of versatile
architectures of 1-4, and their effects on the crystal structures are discussed.
1-4 reveal solid-state photoluminescence stemming from intraligand charge
transfer. 2 and 4 show high selectivity for CO2 over CH4 but with different CO2
adsorption enthalpies. Grand canonical Monte Carlo simulations identified the
multiple adsorption sites in 2 for CO2.
PMID- 27513096
TI - Formation of a Three-Electron Sulfur-Sulfur Bond as a Probe for Interaction
between Side Chains of Methionine Residues.
AB - The mechanism of oxidation processes of l-Met-(Pro)n-l-Met peptides that contain
two Met residues located on the N- and C-terminal and separated by a defined
number (n = 0-4) of proline residues was investigated in aqueous solutions using
pulse radiolysis. The use of such peptides allowed for distance control between
the sulfur atoms located in the side chains of the Met residues. The formation of
a contact between the side chains of the Met residues was probed by the
observation of transients with sigma*-type 2c-3e S?S and S?O bonds as well as of
alpha-(alkylthio)alkyl radicals (alphaS). This approach enabled the monitoring,
in real time, of the efficiency and kinetics of interactions between methionine
side chains. Such knowledge is important, inter alia, for long-distance electron
transfer processes because methionine side chains can serve as relay stations and
also for many aspects of protein folding when the formation of a contact between
two amino acid residues in an unfolded polypeptide chain plays a central role in
protein-folding mechanisms. The yields of these transients (measured as G-values)
were found to be dependent on the number of Pro residues; however, they were not
dependent in a simple way on the average distance ?rS-S? between the sulfur atoms
in Met residues. A decrease in the yield of the (S?S)(+) species with an increase
in the number of Pro residues in the bridge occurred at the expense of an
increase in the yields of the intramolecular three-electron-bonded (S?O)(+)
radical cations and alphaS radicals. A detailed understanding of these trends in
the chemical yields was developed by modeling the underlying chemical kinetics
with Langevin dynamical simulations of the various oligoproline peptide chains
and combining them with a simple statistical mechanical theory on the end-to-end
contact rates for polymer chains. This analysis showed that the formation of a
contact between terminal Met residues in the peptides with 0-2 Pro residues was
controlled by the activated formation of (S?S)(+) whereas in the peptides with 3
and 4 Pro residues, by the relative diffusion of the sulfur radical cation and
unoxidized sulfur atom. In this picture, the dynamics of the other radical
products can be seen to be only indirectly dependent on the length of the proline
bridges because their formation is in competition with (S?S)(+) formation.
PMID- 27513093
TI - Novel Pyrimidine Toll-like Receptor 7 and 8 Dual Agonists to Treat Hepatitis B
Virus.
AB - Toll-like receptor (TLR) 7 and 8 agonists can potentially be used in the
treatment of viral infections and are particularly promising for chronic
hepatitis B virus (HBV) infection. An internal screening effort identified a
pyrimidine Toll-like receptor 7 and 8 dual agonist. This provided a novel
alternative over the previously reported adenine and pteridone type of agonists.
Structure-activity relationship, lead optimization, in silico docking,
pharmacokinetics, and demonstration of ex vivo and in vivo cytokine production of
the lead compound are presented.
PMID- 27513098
TI - Microfluidics-Produced Collagen Fibers Show Extraordinary Mechanical Properties.
AB - Collagens are widely used as biomaterials in drug-delivery and tissue engineering
applications due to their biodegradability, biocompatibility and
hypoallergenicity. Besides gelatin-based materials, collagen microfibers are in
the focus of biomedical research. Commonly, man-made fibers are produced by wet
spinning yielding fiber diameters higher than 8 MUm. Here, assembly and
continuous production of single collagen type I microfibers were established
using a microfluidic chip. Microfluidics-produced microfibers exhibited tensile
strength and Young's modulus exceeding that of fibers produced in classical wet
spinning devices and even that of natural tendon and they showed lower diameters.
Their structural orientation was examined by polarized Fourier transform infrared
spectroscopy (FTIR) showing fibril alignment within the microfiber. Cell culture
tests using the neuronal cell line NG108-15 showed cell alignment and axon growth
along the microfiber axes inaugurating potential applications in, for example,
peripheral nerve repair.
PMID- 27513100
TI - Shrinking the Synchrotron: Tabletop Extreme Ultraviolet Absorption of Transition
Metal Complexes.
AB - We show that the electronic structure of molecular first-row transition-metal
complexes can be reliably measured using tabletop high-harmonic XANES at the
metal M2,3 edge. Extreme ultraviolet photons in the 50-70 eV energy range probe
3p -> 3d transitions, with the same selection rules as soft X-ray L2,3-edge
absorption (2p -> 3d excitation). Absorption spectra of model complexes are
sensitive to the electronic structure of the metal center, and ligand field
multiplet simulations match the shapes and peak-to-peak spacings of the
experimental spectra. This work establishes high-harmonic spectroscopy as a
powerful tool for studying the electronic structure of molecular inorganic,
bioinorganic, and organometallic compounds.
PMID- 27513102
TI - Tissue-engineered human psoriatic skin supplemented with cytokines as an in vitro
model to study plaque psoriasis.
AB - AIM: Psoriasis is a chronic inflammatory skin disease. To study its complex
etiology, a psoriatic skin substitute model supplemented with a cytokine cocktail
has been used. MATERIALS & METHODS: Reconstructed psoriatic skin substitutes were
supplemented with a cocktail of four cytokines: TNF-alpha, IL-1alpha, IL-6 and IL
17A, to monitor their impact on gene expression by DNA microarray. RESULTS: Gene
profiling analyses identified several deregulated genes reported as being also
deregulated in psoriasis skin in vivo (S100A12, IL-8, DEFB4A and KYNU). The
expression of those genes was dramatically increased compared with basal levels
of controls (p < 0.005 to < 0.05). CONCLUSION: Psoriatic substitutes supplemented
with a cocktail of TNF-alpha, IL-1alpha, IL-6 and IL-17A showed similar
transcriptome alterations to those found in psoriasis.
PMID- 27513103
TI - Use of Low-Dose Recombinant Activated Factor VII in the Off-Label Setting: A
Comment to "The Judicious Use of Recombinant Factor VIIa".
PMID- 27513104
TI - Can we improve referrals for fertility preservation? Evolution of practices after
the creation of a fertility network.
PMID- 27513105
TI - KIF21A mutation in two Chinese families with congenital fibrosis of the
extraocular muscles type 1 and 3.
AB - Congenital fibrosis of the extraocular muscles (CFEOM) is a hereditary ocular
disease and can be classified into three subtypes. The aim of the present study
was to determine the genetic basis and describe the clinical phenotype of CFEOM
type 1 and 3. Two Chinese families with CFEOM type 1 and 3 were identified. The
patients and their family members were subjected to comprehensive ophthalmic
examinations, including best-corrected visual acuity, slit-lamp examination,
fundus examination, assessment of palpebral fissure size, levator function,
ocular motility, and cover and forced duction tests. Genomic DNA was extracted
from the leukocytes of venous blood samples collected from the two families and
from 200 unrelated control subjects from the same population. Coding exons of the
KIF21A gene were amplified using polymerase chain reaction analysis and sequenced
directly in the two probands. The detected mutations were further analyzed in all
available family members and the unrelated control subjects. A heterozygous
mutation, c.2860C>T (p.R954W), in KIF21A was identified in the two families, and
this was cosegregated with the presence of the diseases in the two families,
however, it was absent in the 200 normal control subjects. Among the three
affected family members with CFEOM1, differences were observed with regard to the
presence of aberrant eye movement. The results indicated that, in the patients
with CFEOM1 and CFEOM3, the disease was caused by the same KIF21A gene mutation.
The KIF21A gene may be a major disease-causing gene for Chinese patients with
CFEOM3. Phenotypic heterogeneity was observed in the patients with CFEOM1.
PMID- 27513154
TI - Incidence of Neonatal Abstinence Syndrome - 28 States, 1999-2013.
AB - Neonatal abstinence syndrome (NAS) is a postnatal drug withdrawal syndrome that
occurs primarily among opioid-exposed infants shortly after birth, often
manifested by central nervous system irritability, autonomic overreactivity, and
gastrointestinal tract dysfunction (1). During 2000-2012, the incidence of NAS in
the United States significantly increased (2,3). Several recent publications have
provided national estimates of NAS (2,3); however, data describing incidence at
the state level are limited. CDC examined state trends in NAS incidence using all
payer, hospital inpatient delivery discharges compiled in the State Inpatient
Databases of the Healthcare Cost and Utilization Project (HCUP) during 1999-2013.
Among 28 states with publicly available data in HCUP during 1999-2013, the
overall NAS incidence increased 300%, from 1.5 per 1,000 hospital births in 1999,
to 6.0 per 1,000 hospital births in 2013. During the study period, significant
increases in NAS incidence occurred in 25 of 27 states with at least 3 years of
data, with annual incidence rate changes ranging from 0.05 (Hawaii) to 3.6
(Vermont) per 1,000 births. In 2013, NAS incidence ranged from 0.7 cases per
1,000 hospital births (Hawaii) to 33.4 cases per 1,000 hospital births (West
Virginia). The findings underscore the importance of state-based public health
programs to prevent unnecessary opioid use and to treat substance use disorders
during pregnancy, as well as decrease the incidence of NAS.
PMID- 27513155
TI - Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without
Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term
Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG
Z0011 Randomized Trial.
AB - BACKGROUND AND OBJECTIVE: The early results of the American College of Surgeons
Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in locoregional
recurrence for patients with positive sentinel lymph nodes (SLNs) randomized
either to axillary lymph node dissection (ALND) or sentinel lymph node dissection
(SLND) alone. We now report long-term locoregional recurrence results. METHODS:
ACOSOG Z0011 prospectively examined overall survival of patients with SLN
metastases undergoing breast-conserving therapy randomized to undergo ALND after
SLND or no further axillary specific treatment. Locoregional recurrence was
prospectively evaluated and compared between the groups. RESULTS: Four hundred
forty-six patients were randomized to SLND alone and 445 to SLND and ALND. Both
groups were similar with respect to age, Bloom-Richardson score, Estrogen
Receptor status, adjuvant systemic therapy, histology, and tumor size. Patients
randomized to ALND had a median of 17 axillary nodes removed compared with a
median of only 2 SLNs removed with SLND alone (P < 0.001). ALND, as expected,
also removed more positive lymph nodes (P < 0.001). At a median follow-up of 9.25
years, there was no statistically significant difference in local recurrence-free
survival (P = 0.13). The cumulative incidence of nodal recurrences at 10 years
was 0.5% in the ALND arm and 1.5% in the SLND alone arm (P = 0.28). Ten-year
cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P
= 0.36). CONCLUSION: Despite the potential for residual axillary disease after
SLND, SLND without ALND offers excellent regional control for selected patients
with early metastatic breast cancer treated with breast-conserving therapy and
adjuvant systemic therapy.
PMID- 27513156
TI - Per-oral Endoscopic Myotomy (POEM) After the Learning Curve: Durable Long-term
Results With a Low Complication Rate.
AB - OBJECTIVE: We aimed to report long-term outcomes for patients undergoing per-oral
endoscopic myotomy (POEM) after our initial 15-case learning curve. BACKGROUND:
POEM has become an established, natural-orifice surgical approach for treating
esophageal motility disorders. To date, published outcomes and comparative
effectiveness studies have included patients from the early POEM experience.
METHODS: Consecutive patients undergoing POEM after our initial 15 cases, with a
minimum of 1-year postoperative follow-up, were included. Treatment success was
defined as an Eckardt score <=3 without reintervention. Gastroesophageal reflux
was defined by abnormal pH-testing or reflux esophagitis >Los Angeles grade A.
RESULTS: Between January 2012 and March 2015, 115 patients underwent POEM at a
single, high-volume center. Operative time was 101 +/- 29 minutes, with 95%
(109/115) of patients discharged on postoperative day 1. Clavien-Dindo grade III
complications occurred in 2.7%, one of which required diagnostic laparoscopy to
rule out Veress needle injury to the gall bladder. The rate of grade I
complications was 15.2%. At an average of 2.4 years post-POEM (range 12-52
months), the overall success rate was 92%. Objective evidence of reflux was
present in 40% for all patients and 33% for patients with a body mass index <35
kg/m and no hiatal hernia. CONCLUSIONS: POEM performed by experienced surgeons
provided durable symptomatic relief in 94% of patients with nonspastic achalasia
and 90% of patients with type 3 achalasia/spastic esophageal motility disorders,
with a low rate of complications. The rate of gastroesophageal reflux was
comparable with prior studies of both POEM and laparoscopic Heller myotomy.
PMID- 27513157
TI - No Need for Routine Drainage After Pancreatic Head Resection: The Dual-Center,
Randomized, Controlled PANDRA Trial (ISRCTN04937707).
AB - OBJECTIVE: This dual-center, randomized, controlled, noninferiority trial aimed
to prove that omission of drains does not increase reintervention rates after
pancreatic surgery. BACKGROUND: There is considerable uncertainty regarding intra
abdominal drainage after pancreatoduodenectomy. METHODS: Patients undergoing
pancreatic head resection with pancreaticojejunal anastomosis were randomized to
intra-abdominal drainage versus no drainage. Primary endpoint was overall
reintervention rate (relaparotomy or radiologic intervention). Secondary
endpoints were clinically relevant pancreatic fistula (grade B/C), mortality,
morbidity, and hospital stay. The planned sample size was 188 patients per group.
RESULTS: A total of 438 patients were randomized. Forty-three patients (9.8%)
were excluded because no pancreatic anastomosis was performed, and 395 patients
(202 drain, 193 no-drain) were analyzed. Reintervention rates were not inferior
in the no-drain group (drain 21.3%, no-drain 16.6%; P = 0.0004). Overall in
hospital mortality (3.0%) was the same in both groups (drain 3.0%, no-drain 3.1%;
P = 0.936). Overall surgical morbidity (41.8%) was comparable (P = 0.741).
Clinically relevant pancreatic fistula (grade B/C: drain 11.9%, no-drain 5.7%; P
= 0.030) and fistula-associated complications (drain 26.4%; no drain 13.0%; P =
0.0008) were significantly reduced in the no-drain group. Operation time (P =
0.093), postoperative hemorrhage (P = 0.174), intra-abdominal abscess formation
(P = 0.199), biliary leakage (P = 0.382), delayed gastric emptying (P = 0.062),
burst abdomen (P = 0.480), wound infection (P = 0.758), and hospital stay (P =
0.487) did not show significant differences. CONCLUSIONS: Omission of drains was
not inferior to intra-abdominal drainage in terms of postoperative reintervention
and superior in terms of clinically relevant pancreatic fistula rate and fistula
associated complications. There is no need for routine prophylactic drainage
after pancreatic resection with pancreaticojejunal anastomosis.
PMID- 27513159
TI - Photolysis Kinetics of Toluene, Ethylbenzene, and Xylenes at Ice Surfaces.
AB - Benzene, toluene, ethylbenzene, and xylenes (BTEX) are important organic
pollutants. These compounds do not undergo direct photolysis in natural waters
because their absorbance spectra do not overlap with solar radiation at the
Earth's surface. Recent research has suggested that benzene is able to undergo
direct photolysis when present at ice surfaces. However, the photolysis of
toluene, ethylbenzene, and xylenes (TEX) at ice surfaces has not been
investigated. Using fluorescence spectroscopy, photolysis rate constants were
measured for TEX in water, in ice cubes, and in ice granules which reflect
reactivity at ice surfaces. No photolysis was observed in water or ice cubes.
Photolysis was observed in ice granules; rate constants were (4.5 +/- 0.5) * 10(
4) s(-1) (toluene), (5.4 +/- 0.3) * 10(-4) s(-1) (ethylbenzene), and (3.8 +/-
1.2) * 10(-4) s(-1) (xylenes). Photolysis of TEX molecules appears to be enabled
by a red shift in the absorbance spectra at ice surfaces, although
photosensitization may also occur. The results suggest that direct photolysis
could be an important removal pathway for TEX in snow-covered environments.
PMID- 27513160
TI - A structurally flexible triazolate-based metal-organic framework featuring
coordinatively unsaturated copper(i) sites.
AB - The novel metal-organic framework CFA-8 (Coordination Framework Augsburg
University-8), [Cu2(tqpt)], containing the organic linker H2-tqpt {H2-tqpt =
6,6,14,14-tetramethyl-6,14-dihydroquinoxalino[2,3-b]phenazinebis-triazole}, has
been synthesized. Reaction of H2-tqpt and anhydrous CuCl2 in N,N
dimethylacetamide (DMA) yields CFA-8 as orange crystals with lenticular shape.
This framework shows a reversible breathing effect and is robust upon solvent
removal. It has been characterized by single-crystal and powder X-ray
diffraction, TGA, IR spectroscopy and gas sorption measurements. CO adsorption
isotherms show that Cu(i) sites in this framework are able to bind carbon
monoxide forming a weak complex which has been additionally characterized by IR
spectroscopy and synchrotron powder X-ray diffraction measurements.
PMID- 27513161
TI - Effect of UV Photofunctionalization on Osseointegration in Aged Rats.
AB - OBJECTIVES: This study evaluated the effect of photofunctionalization on
osseointegration under the biologically adverse conditions of aging. MATERIALS:
First of all, bone marrow-derived osteoblastic cells from young (8 weeks old) and
aged (15 months old) rats were biologically characterized. Then, the osteoblasts
from aged rats were seeded on titanium discs with and without
photofunctionalization, and assessed for initial cell attachment and osteoblastic
functions. Titanium mini-implants, with and without photofunctionalization, were
placed in the femur of aged rats, and the strength of osseointegration was
measured at week 2 of healing. Periimplant tissue was examined morphologically
and chemically using scanning electron microscopy and energy dispersive x-ray
spectroscopy, respectively. RESULTS: Cells from the aged rats showed
substantially reduced biological capabilities compared with those derived from
young rats. The cells from aged rats showed significantly increased cell
attachment and the expression of osteoblastic function on photofunctionalized
titanium than on untreated titanium. In addition, the strength of
osseointegration was increased by 40% in aged rats carrying the
photofunctionalized implants. Robust bone formation was observed around the
photofunctionalized implants with strong elemental peaks of calcium and
phosphorus, whereas the tissue around untreated implants showed weaker calcium
and phosphate signals than titanium ones. CONCLUSION: These in vivo and in vitro
results corroboratively demonstrate that photofunctionalization is effective for
enhancing osseointegration in aged rats.
PMID- 27513162
TI - Maxillary Sinus Grafting With Biphasic Bone Ceramic or Autogenous Bone: Clinical,
Histologic, and Histomorphometric Results From a Randomized Controlled Clinical
Trial.
AB - PURPOSE: The present, randomized, controlled clinical trial compared the
histologic and histomorphometric results from maxillary sinus augmentation with
either biphasic calcium phosphate (BCP) (60% hydroxyapatite and 40% beta
tricalcium phosphate) or autogenous bone (AB) as bone-grafting materials.
MATERIAL AND METHODS: Ten patients received bilateral sinus elevation surgery
with intraoral AB chips (control group) on one side and BCP (test group) on the
contralateral side. After a healing period of 6 to 8 months, implant sites were
created and trephine cores were harvested for histological and histomorphometric
analysis of the grafted areas. RESULTS: The histological examination of biopsies
showed BCP particles interconnected by bridges of a vital newly formed bone.
Histomorphometry demonstrated that the amount of newly formed bone in the control
group (36.8%) was significantly greater than that in the BCP (28.2%) group (P =
0.0032). BCP and AB cores revealed an average of residual graft particles of
32.9% and 4.8%, respectively. The average percentage of soft tissue components
was 38.9% in the BCP cores and 58.4% in the AB cores. CONCLUSIONS: Based on our
findings, the amount of vital bone formation was significantly higher for AB than
that for BCP. However, BCP seemed to be a biocompatible and osteoconductive
material that can be used with success as a bone substitute in maxillary sinus
procedures.
PMID- 27513163
TI - The Effect of Osteotomy Dimension on Implant Insertion Torque, Healing Mode, and
Osseointegration Indicators: A Study in Dogs.
AB - PURPOSE: This study investigated the effect of the osteotomy diameter for implant
placement torque and its effect on the osseointegration. MATERIALS AND METHODS:
Eight male beagle dogs received 48 implants (3.75 mm * 10 mm) in their right and
left radius, 3 implants per side and allowed to heal for 3 weeks. Three
experimental groups were evaluated. Group 1: implant with an undersized osteotomy
of 3.0 mm; group 2: osteotomy of 3.25 mm, and group 3: osteotomy of 3.5 mm. The
insertion torque was recorded for all implants. Histological sectioning and
histometric analysis were performed evaluating bone-to-implant contact (BIC) and
bone area fraction occupancy (BAFO). RESULTS: Implants of group 1 presented
statistically higher insertion torque than those of groups 2 and 3 (P < 0.01). No
differences in BIC or BAFO were observed between the groups. From a morphologic
standpoint, substantial deviations in healing mode were observed between groups.
CONCLUSION: Based on the present methodology, the experimental alterations of
surgical technic can be clinically used with no detrimental effect over the
osseointegration process.
PMID- 27513164
TI - Direct Construction of 4-Hydroxybenzils via Para-Selective C-C Bond Coupling of
Phenols and Aryl Methyl Ketones.
AB - A highly para-selective C-C bond coupling is presented between phenols C(sp(2))
and aryl methyl ketones C(sp(3)), which enables the direct construction of 4
hydroxybenzil derivatives. This practical method exhibits a broad substrate scope
and large-scale applicability and represents a general gateway to the
hydroxybenzil natural product family. Mechanistic investigations indicated that
the combination of HI with DMSO realized the oxidative carbonylation of aryl
methyl ketones, while boric acid acted as a dual-functional relay reagent to
promote this transformation.
PMID- 27513165
TI - Tubing-Electrospinning: A One-Step Process for Fabricating Fibrous Matrices with
Spatial, Chemical, and Mechanical Gradients.
AB - Guiding newly generated tissues in a gradient pattern, thereby precisely
mimicking inherent tissue morphology and subsequently arranging the intimate
networks between adjacent tissues, is essential to raise the technical levels of
tissue engineering and facilitate its transition into the clinic. In this study,
a straightforward electrospinning method (the tubing-electrospinning technique)
was developed to create fibrous matrices readily with diverse gradient patterns
and to induce patterned cellular responses. Gradient fibrous matrices can be
produced simply by installing a series of polymer-containing lengths of tubing
into an electrospinning circuit and sequentially processing polymers without a
time lag. The loading of polymer samples with different characteristics,
including concentration, wettability, and mechanical properties, into the tubing
system enabled unique features in fibrous matrices, such as longitudinal
gradients in fiber density, surface properties, and mechanical stiffness. The
resulting fibrous gradients were shown to arrange cellular migration and
residence in a gradient manner, thereby offering efficient cues to mediate
patterned tissue formation. The one-step process using tubing-electrospinning
apparatus can be used without significant modifications regardless of the type of
fibrous gradient. Hence, the tubing-electrospinning system can serve as a
platform that can be readily used by a wide-range of users to induce patterned
tissue formation in a gradient manner, which will ultimately improve the
functionality of tissue engineering scaffolds.
PMID- 27513166
TI - Surgical Navigation Technology Based on Augmented Reality and Integrated 3D
Intraoperative Imaging: A Spine Cadaveric Feasibility and Accuracy Study.
AB - STUDY DESIGN: A cadaveric laboratory study. OBJECTIVE: The aim of this study was
to assess the feasibility and accuracy of thoracic pedicle screw placement using
augmented reality surgical navigation (ARSN). SUMMARY OF BACKGROUND DATA: Recent
advances in spinal navigation have shown improved accuracy in lumbosacral pedicle
screw placement but limited benefits in the thoracic spine. 3D intraoperative
imaging and instrument navigation may allow improved accuracy in pedicle screw
placement, without the use of x-ray fluoroscopy, and thus opens the route to
image-guided minimally invasive therapy in the thoracic spine. METHODS: ARSN
encompasses a surgical table, a motorized flat detector C-arm with intraoperative
2D/3D capabilities, integrated optical cameras for augmented reality navigation,
and noninvasive patient motion tracking. Two neurosurgeons placed 94 pedicle
screws in the thoracic spine of four cadavers using ARSN on one side of the spine
(47 screws) and free-hand technique on the contralateral side. X-ray fluoroscopy
was not used for either technique. Four independent reviewers assessed the
postoperative scans, using the Gertzbein grading. Morphometric measurements of
the pedicles axial and sagittal widths and angles, as well as the vertebrae axial
and sagittal rotations were performed to identify risk factors for breaches.
RESULTS: ARSN was feasible and superior to free-hand technique with respect to
overall accuracy (85% vs. 64%, P < 0.05), specifically significant increases of
perfectly placed screws (51% vs. 30%, P < 0.05) and reductions in breaches beyond
4 mm (2% vs. 25%, P < 0.05). All morphometric dimensions, except for vertebral
body axial rotation, were risk factors for larger breaches when performed with
the free-hand method. CONCLUSION: ARSN without fluoroscopy was feasible and
demonstrated higher accuracy than free-hand technique for thoracic pedicle screw
placement. LEVEL OF EVIDENCE: N/A.
PMID- 27513167
TI - The Significance of TRPV4 Channels and Hemichannels in the Lens and Ciliary
Epithelium.
AB - To function normally, all cells must maintain ion homeostasis, establish a
membrane potential, and regulate water content. These actions require active Na-K
transport provided by Na,K-ATPase. The lens, however, is made up almost entirely
of fiber cells that have little or no Na,K-ATPase activity. Lens ion and water
homeostasis rely on Na,K-ATPase activity in a small number of cells at the
periphery of epithelium monolayer. Therefore, the function of the epithelium must
be integrated with the needs of the fiber mass. This suggests that a remote
control mechanism may adjust Na,K-ATPase activity to match increases or decreases
of ion leakage, which may occur a considerable distance away. Here, we review
evidence that TRPV4 channels in the epithelium become activated when the lens is
subjected to osmotic- or damage-induced swelling. This triggers a chain of events
in the lens epithelium that opens connexin hemichannels, allowing ATP release
that stimulates purinergic receptors, activates Src family tyrosine kinases, and
increases Na,K-ATPase activity. Recent studies also revealed functional connexin
hemichannels along with TRPV4 channels in nonpigmented ciliary epithelial (NPE)
cells that secrete aqueous humor into the eye. Because TRPV4 channels are
mechanosensitive, we speculate they might enable the NPE to respond to stimuli
such as mechanical distortion associated with volume homeostasis during fluid
transfer across the ciliary epithelium or changes in intraocular pressure.
PMID- 27513168
TI - Macrolide-Resistant Mycobacterium avium Complex Lung Disease: Analysis of 102
Consecutive Cases.
AB - RATIONALE: The management of macrolide-resistant Mycobacterium avium complex (MR
MAC) pulmonary disease is difficult and is thought to be analogous to that of
multidrug-resistant tuberculosis (MDR-TB). OBJECTIVES: This study aimed to
clarify the cause of MR-MAC, to see how its management affected outcome, and to
compare its prognosis with that of MDR-TB. METHODS: The medical records of 102
consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for
mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to
2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted
from the medical data at Fukujuji Hospital. MEASUREMENTS AND MAIN RESULTS: Of the
90 patients who met the criteria, 53 (58.9%) received inappropriate first-line
treatment, and 28 (31.1%) deviated from the standard treatment because of the
adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB
were not significantly different (P = 0.6). Multivariate analysis showed that the
combination of aminoglycoside and surgery resulted in the best treatment outcome
(P = 0.02), although neither of the two factors reached significance by
themselves. The continuation of clarithromycin and the addition of
fluoroquinolones did not improve the outcome for the treatment of disease caused
by MR-MAC. CONCLUSIONS: Inappropriate prescription patterns and deviations from
the standard treatment because of adverse drug reactions appeared to be the main
causes of macrolide resistance in this patient series. Drug sensitivity testing
should be performed at diagnosis to identify macrolide resistance and patients
who may benefit from other therapy.
PMID- 27513169
TI - Hip-Extensor Strength, Trunk Posture, and Use of the Knee-Extensor Muscles During
Running.
AB - CONTEXT: Diminished hip-muscle performance has been proposed to contribute to
various knee injuries. OBJECTIVE: To determine the association between hip
extensor muscle strength and sagittal-plane trunk posture and the relationships
among hip-extensor muscle strength and hip- and knee-extensor work during
running. DESIGN: Descriptive laboratory study. SETTING: Musculoskeletal
biomechanical laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 40
asymptomatic recreational runners, 20 men (age = 27.1 +/- 7.0 years, height =
1.74 +/- 0.69 m, mass = 71.1 +/- 8.2 kg) and 20 women (age = 26.2 +/- 5.8 years,
height = 1.65 +/- 0.74 m, mass = 60.6 +/- 6.6 kg), participated. MAIN OUTCOME
MEASURE(S): Maximum isometric strength of the hip extensors was assessed using a
dynamometer. Sagittal-plane trunk posture (calculated relative to the global
vertical axis) and hip- and knee-extensor work (sum of energy absorption and
generation) during the stance phase of running were quantified while participants
ran over ground at a controlled speed of 3.4 m/s. We used Pearson product moment
correlations to examine the relationships among hip-extensor strength, mean
sagittal-plane trunk-flexion angle, hip-extensor work, and knee-extensor work.
RESULTS: Hip-extensor strength was correlated positively with trunk-flexion angle
(r = 0.55, P < .001) and hip-extensor work (r = 0.46, P = .003). It was
correlated inversely with knee-extensor work (r = -0.39, P = .01). All the
correlations remained after adjusting for sex. CONCLUSIONS: Our findings suggest
that runners with hip-extensor weakness used a more upright trunk posture. This
strategy led to an overreliance on the knee extensors and may contribute to
overuse running injuries at the knee.
PMID- 27513171
TI - Is More Always Better in Designing Workplace Wellness Programs?: A Comparison of
Wellness Program Components Versus Outcomes.
AB - OBJECTIVE: Assess whether adding more components to a workplace wellness program
is associated with better outcomes by measuring the relationship of program
components to one another and to employee participation and perceptions of
program effectiveness. METHODS: Data came from a 2014 survey of 24,393 employees
of 81 employers about services offered, leadership, incentives, and promotion.
Logistic regressions were used to model the relationship between program
characteristics and outcomes. RESULTS: Components individually are related to
better outcomes, but this relationship is weaker in the presence of other
components and non-significant for incentives. Within components, a moderate
level of services and work time participation opportunities are associated with
higher participation and effectiveness. CONCLUSIONS: The "more of everything"
approach does not appear to be advisable for all programs. Programs should focus
on providing ample opportunities for employees to participate and initiatives
like results-based incentives.
PMID- 27513170
TI - Employee Health Behaviors, Self-Reported Health Status, and Association With
Absenteeism: Comparison With the General Population.
AB - OBJECTIVES: To perform a comparison between health behaviors and health status of
employees with those of the general population, to evaluate the association
between employee health behaviors, health status, and absenteeism. METHODS: Cross
sectional study enrolled 2433 employees from 16 Korean companies in 2014, and
recruited 1000 general population randomly in 2012. The distribution of employee
health behaviors, health status, and association with absenteeism were assessed.
RESULTS: Employees had significantly worse health status and low rates of health
behaviors maintenance compared with the general population. Multiple logistic
regression model revealed that regular exercise, smoking cessation, work life
balance, proactive living, religious practice, and good physical health status
were associated with lower absenteeism. CONCLUSIONS: Maintaining health behaviors
and having good health status were associated with less absenteeism. This study
suggests investment of multidimensional health approach in workplace health and
wellness (WHW) programs.
PMID- 27513172
TI - Associations Between the Self-Reported Frequency of Hearing Chemical Alarms in
Theater and Visuospatial Function in Gulf War Veterans.
AB - OBJECTIVE: The aim of this study was to examine the relationship between the self
reported frequencies of hearing chemical alarms during deployment and
visuospatial function in Gulf War (GW) veterans. METHODS: The relationship
between the self-reported frequency of hearing chemical alarms, neurobehavioral,
and volumetric brain imaging data was examined with correlational, regression,
and mediation analyses. RESULTS: The self-reported frequency of hearing chemical
alarms was inversely associated with and significantly predicted performance on a
visuospatial task (ie, Block Design) over and above potentially confounding
variables, including concurrent, correlated GW-related exposures. This effect was
partially mediated by the relationship between hearing chemical alarms and
lateral occipital cortex volume. CONCLUSIONS: Exposure to substances that
triggered chemical alarms during GW deployment likely had adverse effects on
veterans' brain structure and function, warranting further investigation of
whether these GW veterans are at an increased risk for dementia.
PMID- 27513173
TI - No Association Between Unintentional Head Injuries and Early-Life Exposure to
Tetrachloroethylene (PCE)-Contaminated Drinking Water.
AB - OBJECTIVE: Because of emerging evidence that early-life exposure to the solvent
tetrachloroethylene (PCE) has long-lasting neurological consequences, we examined
the risk of unintentional head injuries following prenatal and childhood exposure
to PCE-contaminated drinking water. METHODS: Participants provided information on
head injuries and other relevant characteristics in a self-administered
questionnaire. Exposure to PCE was modeled using a leaching and transport
algorithm set in water system modeling software. RESULTS: We did not observe any
evidence of an increased risk of any type of head injury among exposed
participants. CONCLUSIONS: PCE is a widespread water pollutant. Thus, documenting
possible health effects of early-life exposure is vital for ensuring that
drinking water regulations adequately protect vulnerable populations.
PMID- 27513174
TI - Numerical cognition explains age-related changes in third-party fairness.
AB - Young children share fairly and expect others to do the same. Yet little is known
about the underlying cognitive mechanisms that support fairness. We investigated
whether children's numerical competencies are linked with their sharing behavior.
Preschoolers (aged 2.5-5.5) participated in third-party resource allocation tasks
in which they split a set of resources between 2 puppets. Children's numerical
competence was assessed using the Give-N task (Sarnecka & Carey, 2008; Wynn,
1990). Numerical competence-specifically knowledge of the cardinal principle
explained age-related changes in fair sharing. Although many subset-knowers
(those without knowledge of the cardinal principle) were still able to share
fairly, they invoked turn-taking strategies and did not remember the number of
resources they shared. These results suggest that numerical cognition serves as
an important mechanism for fair sharing behavior, and that children employ
different sharing strategies (division or turn-taking) depending on their
numerical competence. (PsycINFO Database Record
PMID- 27513175
TI - Highly Sensitive Formation of Stable Surface Relief Structures in Bisanthracene
Films with Spatially Patterned Photopolymerization.
AB - A facile method for the fabrication of a highly sensitive surface relief is
demonstrated, which operates on the principle of spatially patterned
photopolymerization-induced mass transport in the amorphous films of a series of
bisanthracene compounds. The stability of the resultant colorless transparent
relief structure is dramatically improved owing to the polymerization of the
bisanthracene.
PMID- 27513176
TI - Synthesis of the Reported Pyranonaphthoquinone Structure of the Indoleamine-2,3
dioxygenase Inhibitor Annulin B by Regioselective Diels-Alder Reaction.
AB - Annulin B, isolated from the marine hydroid isolated from Garveia annulata, is a
potent inhibitor of the tryptophan catabolizing enzyme indoleamine-2,3
dioxygenase (IDO). A synthesis of the reported pyranonaphthoquinone structure is
described, in which the key step is a regioselective Diels-Alder reaction between
a pyranobenzoquinone dienophile and a silyl ketene acetal diene.
PMID- 27513177
TI - Synthesis, Structure, and Tandem Mass Spectrometric Characterization of the
Diastereomers of Quinic Acid.
AB - (-)-Quinic acid possess eight possible stereoisomers, which occur both naturally
and as products of thermal food processing. In this contribution, we have
selectively synthesized four isomers, namely, epi-quinic acid, muco-quinic acid,
cis-quinic acid, and scyllo-quinic acid, to develop a tandem LC-MS method
identifying all stereoisomeric quinic acids. Four derivatives have been
unambiguously characterized by single-crystal X-ray crystallography. The missing
diastereomers of quinic acid were obtained by nonselective isomerization of (-)
quinic acid using acetic acid/concentrated H2SO4 allowing chromatographic
separation and assignment of all diastereomers of quinic acid. We report for the
first time that a full set of stereoisomers are reliably distinguishable on the
basis of their tandem mass spectrometric fragment spectra as well as their
elution order. A rationale for characteristic fragmentation mechanisms is
proposed. In this study, we also observed that muco-quinic acid, scyllo-quinic
acid, and epi-quinic acid are present in hydrolyzed Guatemalan roasted coffee
sample as possible products of roasting.
PMID- 27513178
TI - Solid-State Synthesis and Structure of the Enigmatic Ammonium Octaborate:
(NH4)2[B7O9(OH)5].3/4B(OH)3.5/4H2O.
AB - The compound known since the 19th century as ammonium octaborate was structurally
characterized revealing the ammonium salt of the ribbon isomer of the heptaborate
anion, [B7O9(OH)5](2-), with boric acid and water molecules. Of composition
(NH4)2B7.75O12.63.4.88H2O, it approximates the classical ammonium octaborate
composition (NH4)2B8O13.6H2O and has the structural formula
{(NH4)2[B7O9(OH)5]}4.3B(OH)3.5H2O. It spontaneously forms at room temperature in
solid-state mixtures of ammonium tetraborate and ammonium pentaborate. It
crystallizes in the monoclinic space group P21/c with a = 11.4137(2) A, b =
11.8877(2) A, c = 23.4459(3) A, beta = 90.092(1) degrees , V = 3181.19(8) A(3),
and Z = 2 and contains well-ordered ammonium cations and [B7O9(OH)5](2-) anions
and disordered B(OH)3 and H2O molecules linked by extensive H bonding.
Expeditious solid-state formation of the heptaborate anion under ambient
conditions has important implications for development of practical syntheses of
industrially useful borates.
PMID- 27513181
TI - Nanoscrews: Asymmetrical Etching of Silver Nanowires.
AB - World's smallest screws with helical threads are synthesized via mild etching of
Ag nanowires. With detailed characterization, we show that this nanostructure
arises not from the transformation of the initial lattice, but the result of a
unique etching mode. Three-dimensional printed models are used to illustrate the
evolution of etch pits, from which a possible mechanism is postulated.
PMID- 27513183
TI - Drug-Specific Design of Telodendrimer Architecture for Effective Doxorubicin
Encapsulation.
AB - Designing a versatile nanocarrier platform that can be tailored to deliver
specific drug payloads is challenging. In general, effective drug encapsulation,
high drug-loading capacity, uniform shape and size distribution, and enhanced
stability are among the fundamental attributes of a successful nanocarrier
design. These physiochemical features of the nanocarriers are intimately tied to
the specific drug payload that they are tasked to deliver. The molecular
architecture of the nanocarrier's scaffold often needs to be tuned for each drug,
especially if the target drugs are structurally and chemically distinct as in the
case of doxorubicin (DOX) and paclitaxel (PTX). Starting from our previously
reported telodendrimeric block copolymer platform optimized for PTX, we analyze
three generations of telodendrimer architectures to arrive at the design that is
capable of encapsulating another important chemotherapeutic drug, DOX. Multiple
long-time-scale self-assembly simulations were performed both in atomistic and
coarse-grained resolutions to generate equilibrated DOX-encapsulated
nanocarriers. The results show how subtle changes in the molecular architecture
of the telodendrimer head groups have profound effects on the nanocarrier size,
morphology, and asphericity. The simulation results are in agreement with the
experimental data for DOX-encapsulated nanocarriers. This work emphasizes the
increasing role of molecular simulations in the rational design of nanocarriers,
thereby eliminating the trial and error method that has been prevalent in
experimental synthesis. The molecular-level insights gained from the simulations
will be used to design the next generation of drug-specific nanocarriers.
PMID- 27513184
TI - Preferential Cancer Cell Self-Recognition and Tumor Self-Targeting by Coating
Nanoparticles with Homotypic Cancer Cell Membranes.
AB - The ultimate goal in cancer therapy and diagnosis is to achieve highly specific
targeting to cancer cells. Coated with the source cancer cell membrane
specifically derived from the homologous tumors, the nanoparticles are identified
with the self-recognition internalization by the source cancer cell lines in
vitro and the highly tumor-selective targeting "homing" to the homologous tumor
in vivo even in the competition of another heterologous tumor. As the result,
MNP@DOX@CCCM nanovehicle showed strong potency for tumor treatment in vivo and
the MR imaging. This bioinspired strategy shows great potential for precise
therapy/diagnosis of various tumors merely by adjusting the cell membrane source
accordingly on the nanoparticle surface.
PMID- 27513186
TI - Two Pathways for Dissociation of Highly Energized syn-CH3CHOO to OH Plus Vinoxy.
AB - Ozonolysis of alkenes is an important nonphotolytic source of hydroxl radicals in
the troposphere. The reaction proceeds through cycloaddition and subsequent
decomposition to a carbonyl oxide, known as Criegee intermediates. Ozonolysis of
alkene releases about 50 kcal/mol excess energy to form highly energized Criegee
molecules, which can be stabilized and undergo further reaction or dissociate to
OH+vinoxy products. The dissociation dynamics of partially stabilized Criegee
(syn-CH3CHOO) has been thoroughly studied recently, in which the molecules
dissociate by first isomerizing to vinyl hydroperoxide (VHP). Here we examine the
dissociation dynamics of highly energized syn-CH3CHOO (42 kcal/mol), and a
second, prompt dissociation path is discovered. The dissociation dynamics of
these two paths are carefully examined through the animation of trajectories and
the energy distributions of products. The new prompt path reveals a distinctly
different translational energy and internal energy distributions of products
compared to the known path through VHP.
PMID- 27513187
TI - Exosomes derived from human mesenchymal stem cells promote gastric cancer cell
growth and migration via the activation of the Akt pathway.
AB - Mesenchymal stem cells (MSCs) are a component of the tumor microenvironment and
can promote the development of gastric cancer through paracrine mechanism.
However, the effects of MSC-exosomes (MSC-ex) on gastric cancer are less clear.
The present study reported that MSC-ex promoted the proliferative and metastatic
potential of gastric cancer cells ex vivo. It was found that MSC-ex enhanced the
migration and invasion of HGC-27 cells via the induction of the epithelial
mesenchymal transition. MSC-ex increased the expression of mesenchymal markers
and reduced the expression of epithelial markers in gastric cancer cells. MSC-ex
also enhanced the tumorigenicity of gastric cancer cells ex vivo. MSC-ex induced
the stemness of gastric cancer cells. The expression of octamer-binding
transcription factor 4, ex determining region Y-box 2 and Lin28B significantly
increased in gastric cancer cells treated with MSC-ex. The present study further
demonstrated that MSC-ex elicited these biological effects predominantly via the
activation of the protein kinase B signaling pathway. Taken together, the present
findings provided novel evidence for the role of MSC-ex in gastric cancer and a
new opportunity for improving the efficiency of gastric cancer treatment by
targeting MSC-ex.
PMID- 27513189
TI - Human-derived feeder fibroblasts for the culture of epithelial cells for clinical
use.
AB - AIM: To investigate human oral mucosal fibroblasts (HOMF) and human limbal
fibroblasts (HLF) as alternatives to murine 3T3 feeder fibroblasts currently used
to support epithelial cell expansion for the treatment of limbal epithelial stem
cell deficiency. METHODS: HLF and HOMF were compared with 3T3s for their ability
to support the culture of human limbal epithelial cells and human oral mucosal
epithelial cells. RESULTS: HOMF, but not HLF, were equivalent to 3T3s in terms of
the number of epithelial population doublings achieved. Human limbal epithelial
cells co-cultured with HOMF or 3T3s had similar expression of corneal and
putative stem cell markers. CONCLUSION: HOMF are a suitable and safer feeder
fibroblast alternative to 3T3s for the production of epithelial cells for
clinical use.
PMID- 27513190
TI - miRNA-24-3p promotes cell proliferation and regulates chemosensitivity in head
and neck squamous cell carcinoma by targeting CHD5.
AB - AIM: To investigate the role of miR-24-3p in tumorigenesis and chemosensitivity
in head and neck squamous cell carcinoma (HNSCC). METHODS: Growth rate and colony
formation assays were performed after transfection with miR-24-3p mimic and
inhibitor in cultured SCC-15 cells, followed by a CellTiter-Glo(r) assay. Western
blot and luciferase assays were performed to investigate the direct target of miR
24-3p. Xenograft mouse model was used to evaluate combinatorial effects of miR-24
3p inhibitor and 5-fluorouracil. RESULTS & CONCLUSION: Inhibition of miR-24-3p
reduced cell proliferation, colony formation efficiency and reversed
chemoresistance in HNSCC cells. CHD5 is the direct target of miR-24-3p which is
required for the regulatory role of miR-24-3p in chemoresistance. miR-24-3p may
represent a new therapeutic target for the improvement of clinical outcome in
HNSCC.
PMID- 27513192
TI - Development of carrier testing for common inborn errors of metabolism in the
Wisconsin Plain population.
AB - PURPOSE: This community project is an initiative through the University of
Wisconsin Biochemical Genetics Clinic and the Wisconsin Newborn Screening Program
to identify members of the Plain population who are at risk for having children
with maple syrup urine disease (MSUD) or propionic acidemia (PA) or who have PA.
METHODS: Because of the high prevalence of metabolic conditions in the Plain
population and the importance of early intervention, a statewide outreach project
was developed to provide targeted variant analysis of the common MSUD and PA
pathogenic variants in this population through health-care provider distribution
of blood spot testing kits. Awareness was achieved through outreach efforts with
the state midwives guild and Plain population meetings. RESULTS: Eighty
individuals were tested; diagnosis was confirmed for three adults with PA and one
couple was identified as being at risk for having a child with PA. Genetic
counseling was provided to those identified. Follow-up diagnostic testing was
completed for the at-risk couple's children; none were found to be affected.
CONCLUSION: This initiative successfully provided accessible clinical testing for
MSUD and PA for a high-risk population. Early identification of at-risk couples
sets the foundation for early care of at-risk neonates, thereby improving future
clinical outcomes.Genet Med 19 3, 352-356.
PMID- 27513191
TI - A placebo-controlled trial of simvastatin therapy in Smith-Lemli-Opitz syndrome.
AB - BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple
malformation/cognitive impairment syndrome characterized by the accumulation of 7
dehydrocholesterol, a precursor sterol of cholesterol. Simvastatin, a 3-hydroxy-3
methylglutaryl-coenzyme A reductase inhibitor that crosses the blood-brain
barrier, has been proposed for the treatment of SLOS based on in vitro and in
vivo studies suggesting that simvastatin increases the expression of hypomorphic
DHCR7 alleles. METHODS: Safety and efficacy of simvastatin therapy in 23 patients
with mild to typical SLOS were evaluated in a randomized, double-blind, placebo
controlled trial. The crossover trial consisted of two 12-month treatment phases
separated by a 2-month washout period. RESULTS: No safety issues were identified
in this study. Plasma dehydrocholesterol concentrations decreased significantly:
8.9 +/- 8.4% on placebo to 6.1 +/- 5.5% on simvastatin (P < 0.005); we observed a
trend toward decreased cerebrospinal fluid dehydrocholesterol concentrations. A
significant improvement (P = 0.017, paired t-test) was observed on the
irritability subscale of the Aberrant Behavior Checklist-C when subjects were
taking simvastatin. CONCLUSION: This article reports what is, to our knowledge,
the first randomized, placebo-controlled trial designed to test the safety and
efficacy of simvastatin therapy in SLOS. Simvastatin seems to be relatively safe
in patients with SLOS, improves the serum dehydrocholesterol-to-total sterol
ratio, and significantly improves irritability symptoms in patients with mild to
classic SLOS.Genet Med 19 3, 297-305.
PMID- 27513193
TI - Candidate-gene criteria for clinical reporting: diagnostic exome sequencing
identifies altered candidate genes among 8% of patients with undiagnosed
diseases.
AB - PURPOSE: Diagnostic exome sequencing (DES) is now a commonly ordered test for
individuals with undiagnosed genetic disorders. In addition to providing a
diagnosis for characterized diseases, exome sequencing has the capacity to
uncover novel candidate genes for disease. METHODS: Family-based DES included
analysis of both characterized and novel genetic etiologies. To evaluate
candidate genes for disease in the clinical setting, we developed a systematic,
rule-based classification schema. RESULTS: Testing identified a candidate gene
among 7.7% (72/934) of patients referred for DES; 37 (4.0%) and 35 (3.7%) of the
genes received evidence scores of "candidate" and "suspected candidate,"
respectively. A total of 71 independent candidate genes were reported among the
72 patients, and 38% (27/71) were subsequently corroborated in the peer-reviewed
literature. This rate of corroboration increased to 51.9% (27/52) among patients
whose gene was reported at least 12 months previously. CONCLUSIONS: Herein, we
provide transparent, comprehensive, and standardized scoring criteria for the
clinical reporting of candidate genes. These results demonstrate that DES is an
integral tool for genetic diagnosis, especially for elucidating the molecular
basis for both characterized and novel candidate genetic etiologies. Gene
discoveries also advance the understanding of normal human biology and more
common diseases.Genet Med 19 2, 224-235.
PMID- 27513194
TI - Personalized risk prediction for type 2 diabetes: the potential of genetic risk
scores.
AB - PURPOSE: Using effect estimates from genome-wide association studies (GWAS), we
identified a genetic risk score (GRS) that has the strongest association with
type 2 diabetes (T2D) status in a population-based cohort and investigated its
potential for prospective T2D risk assessment. METHODS: By varying the number of
single-nucleotide polymorphisms (SNPs) and their respective weights, alternative
versions of GRS can be computed. They were tested in 1,181 T2D cases and 9,092
controls of the Estonian Biobank cohort. The best-fitting GRS was chosen for the
subsequent analysis of incident T2D (386 cases). RESULTS: The best fit was
provided by a novel doubly weighted GRS that captures the effect of 1,000 SNPs.
The hazard for incident T2D was 3.45 times (95% CI: 2.31-5.17) higher in the
highest GRS quintile compared with the lowest quintile, after adjusting for body
mass index and other known predictors. Adding GRS to the prediction model for 5
year T2D risk resulted in continuous net reclassification improvement of 0.324
(95% CI: 0.211-0.444). In addition, a significant effect of the GRS on all-cause
and cardiovascular mortality was observed. CONCLUSION: The proposed GRS would
improve the accuracy of T2D risk prediction when added to the currently used set
of predictors.Genet Med 19 3, 322-329.
PMID- 27513195
TI - Medical applications of Cu, Zn, and S isotope effects.
AB - This review examines recent applications of stable copper, zinc and sulfur
isotopes to medical cases and notably cancer. The distribution of the natural
stable isotopes of a particular element among coexisting molecular species varies
as a function of the bond strength, the ionic charge, and the coordination, and
it also changes with kinetics. Ab initio calculations show that compounds in
which a metal binds to oxygen- (sulfate, phosphate, lactate) and nitrogen-bearing
moieties (histidine) favor heavy isotopes, whereas bonds with sulfur (cysteine,
methionine) favor light isotopes. Oxidized cations (e.g., Cu(ii)) and low
coordination numbers are expected to favor heavy isotopes relative to their
reduced counterparts (Cu(i)) and high coordination numbers. Here we discuss the
first observations of Cu, Zn, and S isotopic variations, three elements closely
related along multiple biological pathways, with emphasis on serum samples of
healthy volunteers and of cancer patients. It was found that heavy isotopes of Zn
and to an even greater extent Cu are enriched in erythrocytes relative to serum,
while the difference is small for sulfur. Isotopic variations related to age and
sex are relatively small. The 65Cu/63Cu ratio in the serum of patients with
colon, breast, and liver cancer is conspicuously low relative to healthy
subjects. The characteristic time over which Cu isotopes may change with disease
progression (a few weeks) is consistent with both the turnover time of the
element and albumin half-life. A parallel effect on sulfur isotopes is detected
in a few un-medicated patients. Copper in liver tumor tissue is isotopically
heavy. In contrast, Zn in breast cancer tumors is isotopically lighter than in
healthy breast tissue. 66Zn/64Zn is very similar in the serum of cancer patients
and in controls. Possible reasons for Cu isotope variations may be related to the
cytosolic storage of Cu lactate (Warburg effect), release of intracellular copper
from cysteine clusters (metallothionein), or the hepatocellular and biosynthetic
dysfunction of the liver. We suggest that Cu isotope metallomics will help
evaluate the homeostasis of this element during patient treatment, notably by
chelates and blockers of Cu trafficking, and understand the many biochemical
pathways in which this element is essential.
PMID- 27513196
TI - The Time-Dependent Transfer Factor of Radiocesium from Soil to Game Animals in
Japan after the Fukushima Dai-ichi Nuclear Accident.
AB - Since the Fukushima Dai-ichi accident, monitoring of tissues from hunted game
animals ensures compliance with the standard food limits for radionuclides in
Japan. We quantified the transfer of (137)Cs from contaminated land to game
animals using the Aggregated transfer factor (Tag = activity concentration in
meat [Bq kg(-1) fw]/amount in soil [Bq m(-2)]) of (137)Cs for Asian black bear,
wild boar, sika deer, green pheasant, copper pheasant and wild duck, collected
between 2011 and 2015. Open data sources were used from Fukushima, Miyagi,
Ibaraki, Tochigi, and Gunma prefectures. Our initially compiled data showed that
the maximum reported (137)Cs activity concentration in wild boar after the
Fukushima Dai-ichi accident were lower than those reported after the Chernobyl
accident. The geometric mean Tag values (m(2)kg(-1) fw) of (137)Cs in 2015 for
Asian black bear, wild boar, sika deer and copper pheasant were similar (1.9-5.1)
* 10(-3) while those for green pheasant and wild duck were about 1 order of
magnitude lower at (1.0-2.2) * 10(-4). Effective half-lives were 1.2-6.9 y except
for sika deer and copper pheasant where no decreases were found. In contrast to
the Chernobyl accident, no seasonal change occurred in the meat (137)Cs activity
concentrations of the wild animals during the study period.
PMID- 27513197
TI - Auditory capture of visual motion: effects on perception and discrimination.
AB - We asked whether the perceived direction of visual motion and contrast thresholds
for motion discrimination are influenced by the concurrent motion of an auditory
sound source. Visual motion stimuli were counterphasing Gabor patches, whose net
motion energy was manipulated by adjusting the contrast of the leftward-moving
and rightward-moving components. The presentation of these visual stimuli was
paired with the simultaneous presentation of auditory stimuli, whose apparent
motion in 3D auditory space (rightward, leftward, static, no sound) was
manipulated using interaural time and intensity differences, and Doppler cues. In
experiment 1, observers judged whether the Gabor visual stimulus appeared to move
rightward or leftward. In experiment 2, contrast discrimination thresholds for
detecting the interval containing unequal (rightward or leftward) visual motion
energy were obtained under the same auditory conditions. Experiment 1 showed that
the perceived direction of ambiguous visual motion is powerfully influenced by
concurrent auditory motion, such that auditory motion 'captured' ambiguous visual
motion. Experiment 2 showed that this interaction occurs at a sensory stage of
processing as visual contrast discrimination thresholds (a criterion-free measure
of sensitivity) were significantly elevated when paired with congruent auditory
motion. These results suggest that auditory and visual motion signals are
integrated and combined into a supramodal (audiovisual) representation of motion.
PMID- 27513198
TI - Is the Wnt/beta-catenin pathway involved in the anti-inflammatory activity of
glucocorticoids in spinal cord injury?
AB - The Wnt canonical or the Wnt/beta-catenin pathway has been implicated in the
regulation of several physiopathological pathways such as inflammation.
Glucocorticoids (GCs) are administered widely to treat inflammation in several
diseases, including spinal cord injury (SCI). The aim of this study was to
evaluate whether the Wnt canonical pathway is involved in experimental SCI and
whether it is implicated in the anti-inflammatory activity of two different GCs:
the methylprednisolone sodium succinate (MPSS), considered the standard treatment
for acute SCI, and mometasone furoate (MF), mainly administered for the treatment
of airway and skin diseases. Experimental SCI was induced in mice by surgical
spinal cord compression at the T6-T7 level. Then, mice were treated with MPSS (6
mg/kg) or MF (0.1 mg/kg) for 7 days until they were killed. Both GCs were found
to modulate the Wnt canonical pathway, but in particular, the MF treatment was
shown to restore completely the downregulated pathway in SCI. The MF treatment
also significantly increased peroxisome proliferator-activated receptor-gamma, a
Wnt target gene with anti-inflammatory properties, compared with MPSS, and it
also inhibited the levels of the proinflammatory cytokines interleukin 1beta and
tumor necrosis factor-alpha. Here, we suggest that MF has more efficacy than MPSS
in inhibiting inflammation in an SCI experimental model and we propose the beta
catenin/peroxisome proliferator-activated receptor-gamma axis as the mechanism by
which MF exerts these beneficial effects.
PMID- 27513199
TI - Isoflurane attenuates mouse microglial engulfment induced by lipopolysaccharide
and interferon-gamma possibly by inhibition of p38 mitogen-activated protein
kinase.
AB - Microglial engulfment is a basic function to clean up dead and injured cells and
invaders, such as bacteria. This study was designed to assess the effects of
isoflurane on the microglial engulfment induced by lipopolysaccharide (LPS) plus
interferon-gamma (IFN-gamma) and the involvement of p38 mitogen-activated protein
kinase (MAPK) in these effects. C8-B4 microglial cells were exposed to 1, 2, and
3% isoflurane at 2 h after the initiation of LPS (100 ng/ml) and IFN-gamma (1
ng/ml) stimulation. Fluorescent immunostaining was performed to assess the
percentage of cells with engulfment of fluorescent microspheres after stimulation
for 24 h. P38 and phosphorylated p38 were determined by Western blotting.
Isoflurane concentration dependently decreased microglial engulfment stimulated
by LPS and IFN-gamma. LPS and IFN-gamma increased the phosphorylated p38 in
microglial cells. This upregulation was decreased by isoflurane. SB203580, a p38
MAPK inhibitor, abolished the LPS-induced and IFN-gamma-induced increase of
engulfment activity, whereas anisomycin, a p38 MAPK activator, partly reversed
the isoflurane-decreased microglial engulfment activity. These results suggest
that isoflurane reduces LPS-induced and IFN-gamma-induced microglial engulfment
and that these effects may be mediated by inhibiting p38 MAPK.
PMID- 27513200
TI - Temporal prediction restores the evaluative processing of delayed action
feedback: an electrophysiological study.
AB - The evaluative processing of the valence of action feedback is reflected by an
event-related brain potential component called feedback-related negativity (FRN)
or reward positivity (RewP). Recent studies have shown that FRN/RewP is markedly
reduced when the action-feedback interval is long (e.g. 6000 ms), indicating that
an increase in the action-feedback interval can undermine the evaluative
processing of the valence of action feedback. The aim of the present study was to
investigate whether or not such undermined evaluative processing of delayed
action feedback could be restored by improving the accuracy of the prediction in
terms of the timing of action feedback. With a typical gambling task in which the
participant chose one of two cards and received an action feedback indicating
monetary gain or loss, the present study showed that FRN/RewP was significantly
elicited even when the action-feedback interval was 6000 ms, when an auditory
stimulus sequence was additionally presented during the action-feedback interval
as a temporal cue. This result suggests that the undermined evaluative processing
of delayed action feedback can be restored by increasing the accuracy of the
prediction on the timing of the action feedback.
PMID- 27513201
TI - Protective effects of quercetin on dieldrin-induced endoplasmic reticulum stress
and apoptosis in dopaminergic neuronal cells.
AB - Dieldrin, an organochlorine pesticide still used in several developing countries,
has been proposed as a risk factor for Parkinson's disease. Quercetin is one of
the potent bioactive flavonoids present in numerous plants. In this study, we
investigated the protective effects of quercetin on neurotoxicity induced by
dieldrin in cultured dopaminergic SN4741 cells. Our initial experiments showed
that quercetin (10-40 MUM) dose dependently prevented dieldrin (20 MUM)-induced
cytotoxicity in SN4741 cells. Pretreatment for 1 h with quercetin before dieldrin
application could significantly suppress dieldrin-induced apoptotic
characteristics, including nuclear condensation, DNA fragmentation, and caspase
3/7 activation. Results showed that dieldrin-induced markers of endoplasmic
reticulum (ER) stress response such as chaperone GRP78, heme oxygenase-1, and
phosphorylation of the alpha subunit of eukaryotic initiation factor 2. In
addition, dieldrin reduced antiapoptotic Bcl-2 expression, but significantly
elevated a proapoptotic transcription factor CHOP. Furthermore, RNA interference
to CHOP almost completely repressed dieldrin-induced apoptotic cell death.
Interestingly, quercetin prevented the changes in dieldrin-induced ER stress
markers. These results suggest that quercetin may suppress the ER stress-CHOP
pathway and dieldrin-induced apoptosis in dopaminergic neurons.
PMID- 27513202
TI - Differentiated adipose-derived stem cells promote the recovery of nociceptor
function in rats.
AB - The loss of nociceptive function in the skin because of trauma or surgery can
impair the quality of life. The recovery of nociceptor function is mediated by
two different axonal responses: nerve growth factor (NGF)-dependent collateral
sprouting of undamaged nerves and NGF-independent regeneration of damaged nerves.
We reported previously that adipose-derived stem cells (ASCs) can
transdifferentiate into Schwann cell (SC)-like cells (dASCs) and that
transplantation of dASCs increases axonal density in skin flaps. In the present
study, we used an animal model that allowed for the individual assessment of
collateral sprouting and regeneration. In-vitro differentiation of ASCs to dASCs
significantly increased the production of NGF and brain-derived neurotrophic
factor (BDNF) to levels comparable with SCs. In-vivo experiments showed that dASC
and SC transplantation significantly increased the area of the mechano
nociceptive field in both collateral sprouting and regeneration models, whereas
ASC transplantation exerted no significant effect. Antibody blocking experiment
showed that these effects of dASC transplantation in the regeneration model were
partly mediated by BDNF. Interestingly, the final areas of nociceptive fields
between the two experimental models did not differ significantly for any
treatment condition. These results indicate that dASC transplantation
differentially facilitates collateral sprouting and axonal regeneration by
delivering NGF and other neurotrophic factors (e.g. BDNF), respectively. Although
there is a limit to nociceptive field enlargement irrespective of axonal
response, dASC transplantation could present a new approach for improving
nociceptive function in denervated skin.
PMID- 27513203
TI - Molecular cloning, expression analysis and miRNA prediction of vascular
endothelial growth factor A (VEGFAa and VEGFAb) in pond loach Misgurnus
anguillicaudatus, an air-breathing fish.
AB - Vascular endothelial growth factor A (VEGFA) is the most studied and the best
characterized member of the VEGF family and is a key regulator of angiogenesis
via its ability to affect the proliferation, migration, and differentiation of
endothelial cells. In this study, the full-length cDNAs encoding VEGFAa and
VEGFAb from pond loach, Misgurnus anguillicaudatus, were isolated. The VEGFAa is
constituted by an open reading frame (ORF) of 570bp encoding for a peptide of 189
amino acid residues, a 639bp 5'-untranslated region (UTR) and a 2383bp 3' UTR.
The VEGFAb is constituted by an ORF of 687bp encoding for a peptide of 228 amino
acid residues, a 560bp 5' UTR and a 1268bp 3' UTR. Phylogenetic analysis
indicated that the VEGFAa and VEGFAb of pond loach were conserved in vertebrates.
Expression levels of VEGFAa and VEGFAb were detected by RT-qPCR at different
development stages of pond loach and in different tissues of 6-month-old, 12
month-old and 24-month-old pond loach. Moreover, eight predicted miRNAs (miR-200,
miR-29, miR-218, miR-338, miR-103, miR-15, miR-17 and miR-223) targeting VEGFAa
and VEGFAb were validated by an intestinal air-breathing inhibition experiment.
This study will be of value for further studies into the function of VEGFA and
its corresponding miRNAs, which will shed a light on the vascularization and
accessory air-breathing process in pond loach.
PMID- 27513204
TI - The use of brincidofovir for the treatment of mixed dsDNA viral infection.
AB - Double-stranded DNA (dsDNA) viral infections constitute a major complication
following solid organ and stem cell transplantation. Few therapeutic options are
currently available for the treatment of such infections in highly
immunocompromised hosts. Brincidofovir is an oral investigational drug with broad
antiviral activity against dsDNA viruses in vitro, but clinical experience is
limited. Here we report a young female who developed a mixed infection with
adenovirus, cytomegalovirus, Epstein-Barr virus and BK polyomavirus after an
allogeneic stem cell transplant, and was successfully treated with brincidofovir.
PMID- 27513205
TI - Toxoplasma gondii Infection Potentiates Cognitive Impairments of Alzheimer's
Disease in the BALB/c Mice.
AB - This study tests the hypothesis that in chronic Toxoplasma gondii infection
communication among immune cells promotes neuroinflammation through cytokine
networks and potentiate cognitive impairments in BALB/c mice with Alzheimer's
disease (AD). The animal model of Toxoplasma infection was established by the
intraperitoneal inoculation of 20-25 tissue cysts from the Tehran strain of T.
gondii . We injected amyloid-beta 1-42 peptide (Abeta1-42, 1 and 2 MUl) into the
hippocampus of BALB/c mice to establish an animal model of AD. The behavioral
experiments such as spatial learning and memory were performed using the Morris
water maze test. The mRNA levels of TNF-alpha, IL-1beta, IFN-gamma, and inducible
nitric oxide synthase (iNOS) were examined by real-time PCR. We found that T.
gondii infection caused AD-like symptoms and impaired learning and memory
functions of the infected BALB/c mice. We also found that in Toxoplasma infection
+ Abeta1-42 (1 MUl) group, T. gondii infection could potentiate AD in infected
mice receiving subdoses of Abeta1-42 (1 MUl) and caused considerable impairment
in learning and memory functions similar to AD group. Comparison of the results
demonstrated that mRNA levels of IL-1beta, TNF-alpha, IFN-gamma, and iNOS
significantly (P < 0.001) increased in T. gondii + Abeta1-42 (1 MUl) in
comparison with the other tested groups. The obtained results showed that chronic
T. gondii infection communication among immune cells promotes neuroinflammation
through cytokine networks and induces pathological progression of AD in the mice
brain, whereas the presence of neuroanatomical Toxoplasma tissue cysts in the
brain could also affect the behavioral functions in T. gondii -infected mice.
PMID- 27513206
TI - Evaluating the Impact of National Public Health Department Accreditation - United
States, 2016.
AB - In 2011, the nonprofit Public Health Accreditation Board (PHAB) launched the
national, voluntary public health accreditation program for state, tribal, local,
and territorial public health departments. As of May 2016, 134 health departments
have achieved 5-year accreditation through PHAB and 176 more have begun the
formal process of pursuing accreditation. In addition, Florida, a centralized
state in which the employees of all 67 local health departments are employees of
the state, achieved accreditation for the entire integrated local public health
department system in the state. PHAB-accredited health departments range in size
from a small Indiana health department that serves approximately 17,000 persons
to the much larger California Department of Public Health, which serves
approximately 38 million persons. Collectively, approximately half the U.S.
population, or nearly 167 million persons, is covered by an accredited health
department. Forty-two states and the District of Columbia now have at least one
nationally accredited health department. In a survey conducted through a contract
with a social science research organization during 2013-2016, >90% of health
departments that had been accredited for 1 year reported that accreditation has
stimulated quality improvement and performance improvement opportunities,
increased accountability and transparency, and improved management processes.
PMID- 27513207
TI - Ultrasound harmonic enhanced imaging using eigenspace-based coherence factor.
AB - Tissue harmonic imaging (THI) utilizes harmonic signals generating within the
tissue as the result of nonlinear acoustic wave propagation. With inadequate
transmitting acoustic energy, THI is incapable to detect the small objects since
poor harmonic signals have been generated. In most cases, high transmission
energy cannot be guaranteed because of the imaging safety issue or specific
imaging modality such as the plane wave imaging (PWI). Discrimination of small
point targets such as calcification, however, is particularly important in the
ultrasound diagnosis. Few efforts have been made to pursue the THI with high
resolution and good small target visibility at the same time. In this paper, we
proposed a new eigenspace-based coherence factor (ESBCF) beamformer to solve this
problem. A new kind of coherence factor (CF), named as ESBCF, is firstly proposed
to detect the point targets. The detected region-of-interest (ROI) is then
enhanced adaptively by using a newly developed beamforming method. The ESBCF
combines the information from signal eigenspace and coherence factor by expanding
the CF to the covariance matrix of signal. Analogous to the image processing but
in the radio frequency (RF) data domain, the proposed method fully utilizes the
information from the fundamental and harmonic components. The performance of the
proposed method is demonstrated by simulation and phantom experiments. The
improvement of the point contrast ratio (PCR) is 7.6dB in the simulated data, and
6.0dB in the phantom experiment. Thanks to the improved small point detection
ability of the ESBCF, the proposed beamforming algorithm can enhance the PCR
considerably and maintain the high resolution of the THI at the same time.
PMID- 27513208
TI - NMR Spectra Transformed by Electron-Nuclear Coupling as Indicator of Structural
Peculiarities of Magnetically Active Molecular Systems.
AB - The peculiarities of nuclear spin relaxation in the paramagnetic systems have
been analyzed taking into account the exchange processes. The analysis is based
on the modified Solomon-Bloembergen equations. In this line, the conditions of
detecting of the NMR signals of samples are discussed depending on resonance
frequency of the NMR spectrometer and characteristic relaxation time. On this
basis, (1)H NMR spectra of cobalt semiquinolate complex have been analyzed. It
has been shown that the satellite signals observed in the spectrum are caused by
hyperfine coupling of the tert-butyl group protons with alpha and beta states
(localized on pz orbital of the aromatic carbon) of unpaired electron spin. The
relaxation process of the resonance protons is controlled by paramagnetic dipole
dipole coupling. The contact hyperfine coupling does not contribute to the
paramagnetic broadening. A mechanism involving paramagnetic molecular structures,
which are responsible for intramolecular exchange processes in the cobalt
semiquinolate complex, is given.
PMID- 27513209
TI - Inhibition of coagulation proteases Xa and IIa decreases ischemia-reperfusion
injuries in a preclinical renal transplantation model.
AB - Coagulation is an important pathway in the pathophysiology of ischemia
reperfusion injuries. In particular, deceased after circulatory death (DCD)
donors undergo a no-flow period, a strong activator of coagulation. Hence,
therapies influencing the coagulation cascade must be developed. We evaluated the
effect of a new highly specific and effective anti-Xa/IIa molecule, with an
integrated innovative antidote site (EP217609), in a porcine preclinical model
mimicking injuries observed in DCD donor kidney transplantation. Kidneys were
clamped for 60 minutes (warm ischemia), then flushed and preserved for 24 hours
at 4 degrees C in University of Wisconsin (UW) solution (supplemented or not).
EP217609-supplemented UW solution (UW-EP), compared with unfractionated heparin
supplemented UW solution (UW-UFH) or UW alone (UW). A mechanistic investigation
was conducted in vitro: addition of EP217609 to endothelial cells during hypoxia
at 4 degrees C in the UW solution inhibited thrombin generation during
reoxygenation at 37 degrees C in human plasma and reduced tumor necrosis factor
alpha, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1
messenger RNA cell expressions. In vivo, function recovery was markedly improved
in the UW-EP group. Interestingly, levels of thrombin-antithrombin complexes
(reflecting thrombin generation) were reduced 60 minutes after reperfusion in the
UW-EP group. In addition, 3 months after transplantation, lower fibrosis,
epithelial-mesenchymal transition, inflammation, and leukocyte infiltration were
observed. Using this new dual anticoagulant, anti-Xa/IIa activity during kidney
flush and preservation is protected by reducing thrombin generation at
revascularization, improving early function recovery, and decreasing chronic
lesions. Such an easy-to-deploy clinical strategy could improve marginal graft
outcome.
PMID- 27513212
TI - Therapeutic potential of Taraxacum officinale against HCV NS5B polymerase: In
vitro and In silico study.
AB - Discovery of alternative and complementary regimens for HCV infection treatment
is a need of time from clinical as well as economical point of views. Low cost of
bioactive natural compounds production, high biochemical diversity and
inexistent/milder side effects contribute to new therapies. Aim of this study is
to clarify anti-HCV role of Taraxacum officinale, a natural habitat plant rich of
flavonoids. In this study, methanol extract of T. officinale leaves was initially
analyzed for its cytotoxic activity in human hepatoma (Huh-7) and CHO cell lines.
Hepatoma cells were transfected with pCR3.1/Flagtag/HCV NS5B gene cloned vector
(genotype 1a) along with T. officinale extract. Considering NS5B polymerase as
potential therapeutic drug target, twelve phytochemicals of T. officinale were
selected as ligands for molecular interaction with NS5B protein using Molecular
Operating Environment (MOE) software. Sofosbuvir (Sovaldi: brand name) currently
approved as new anti-HCV drug, was used as standard in current study for
comparative analysis in computational docking screening. HCV NS5B polymerase as
name indicates plays key role in viral genome replication. On the basis of which
NS5B gene is targeted for determining antiviral role of T. officinale extract and
65% inhibition of NS5B expression was documented at nontoxic dose concentration
(200MUg/ml) using Real-time PCR. In addition, 57% inhibition of HCV replication
was recorded when incubating Huh-7 cells with high titer serum of HCV infected
patients along with leaves extract. Phytochemicals for instance d-glucopyranoside
(-31.212 Kcal/mol), Quercetin (-29.222 Kcal/mol), Luteolin (-26.941 Kcal/mol) and
some others displayed least binding energies as compared to standard drug
Sofosbuvir (-21.0746 Kcal/mol). Results of our study strongly revealed that T.
officinale leaves extract potentially blocked the viral replication and NS5B gene
expression without posing any toxic effect on normal fibroblast cells of body.
PMID- 27513211
TI - Toward revision of antimicrobial therapies in hematopoietic stem cell
transplantation: target the pathogens, but protect the indigenous microbiota.
AB - Host microbiota plays important roles in providing colonization resistance to
pathogens and instructing development and function of the immune system.
Antibiotic treatments intended to target pathogens further weaken the host
defenses and may paradoxically increase the risk of systemic infections. This
consequence is especially problematic in patients undergoing hematopoietic stem
cell transplantation, where the mucosal defenses are already weakened by the
conditioning regimens. This review discusses the roles that indigenous microbiota
plays in protecting the host and maintaining immune homeostasis. In addition, we
highlight possible strategies that are being developed to allow targeted
antimicrobial therapy against pathogens, while minimizing the harm to indigenous
microbiota.
PMID- 27513213
TI - Synergistic production of TNFalpha and IFNalpha by human pDCs incubated with
IFNlambda3 and IL-3.
AB - In this study, we investigated whether IFNlambda3 and IL-3 reciprocally influence
their capacity to activate various functions of human plasmacytoid dendritic
cells (pDCs). In fact, we preliminarily observed that IFNlambda3 upregulates the
expression of the IL-3Ralpha (CD123), while IL-3 augments the expression of
IFNlambdaR1 in pDCs. As a result, we found that combination of IFNlambda3 and IL
3 induces a strong potentiation in the production of TNFalpha, IFNalpha, as well
as in the expression of Interferon-Stimulated Gene (ISG) mRNAs by pDCs, as
compared to either IFNlambda3 or IL-3 alone. In such regard, we found that
endogenous IFNalpha autocrinally promotes the expression of ISG mRNAs in IL-3-,
but not in IFNlambda3 plus IL-3-, treated pDCs. Moreover, we uncovered that the
production of IFNalpha by IFNlambda3 plus IL-3-treated pDCs is mostly dependent
on endogenously produced TNFalpha. Altogether, our data demonstrate that
IFNlambda3 and IL-3 collaborate to promote, at maximal levels, discrete
functional responses of human pDCs.
PMID- 27513214
TI - Assembly and Folding of Twisted Baskets in Organic Solvents.
AB - A synthetic method for obtaining enantiopure and twisted baskets of type (P)-3 is
described. These chiral cavitands were found to fold quinoline gates, at the rim
of their twisted platform, in acetonitrile and give molecular capsules that
assemble into large unilamellar vesicles. In a less polar dichloromethane,
however, cup-shaped (P)-3 packed into vesicles but with the quinoline gates in an
unfolded orientation. The ability of twisted baskets to form functional
nanostructured materials could be of interest for building stereoselective
sensors and catalysts.
PMID- 27513210
TI - High-resolution characterization of the human microbiome.
AB - The human microbiome plays an important and increasingly recognized role in human
health. Studies of the microbiome typically use targeted sequencing of the 16S
rRNA gene, whole metagenome shotgun sequencing, or other meta-omic technologies
to characterize the microbiome's composition, activity, and dynamics. Processing,
analyzing, and interpreting these data involve numerous computational tools that
aim to filter, cluster, annotate, and quantify the obtained data and ultimately
provide an accurate and interpretable profile of the microbiome's taxonomy,
functional capacity, and behavior. These tools, however, are often limited in
resolution and accuracy and may fail to capture many biologically and clinically
relevant microbiome features, such as strain-level variation or nuanced
functional response to perturbation. Over the past few years, extensive efforts
have been invested toward addressing these challenges and developing novel
computational methods for accurate and high-resolution characterization of
microbiome data. These methods aim to quantify strain-level composition and
variation, detect and characterize rare microbiome species, link specific genes
to individual taxa, and more accurately characterize the functional capacity and
dynamics of the microbiome. These methods and the ability to produce detailed and
precise microbiome information are clearly essential for informing microbiome
based personalized therapies. In this review, we survey these methods,
highlighting the challenges each method sets out to address and briefly
describing methodological approaches.
PMID- 27513215
TI - Protective effects of miR-25 against hypoxia/reoxygenation-induced fibrosis and
apoptosis of H9c2 cells.
AB - It has been previously demonstrated that microRNA (miR)-25 plays critical roles
in collagen deposition. Ischemia/reperfusion injury to the myocardium results in
fibrosis and collagen deposition. However, whether miR-25 is involved in the
development of hypoxia/reoxygenation (H/R)-induced fibrosis in cardiomyocytes or
not remains largely unknown. For this purpose, in the present study,
cardiomyocyte H9c2 cells were subjected to H/R. The techniques of flow cytometry,
western blot analysis and RT-qPCR were used and we observed increases in the cell
apoptosis rate and fibrosis as well as blocking of the cell cycle in the G1
phase. Moreover, the expression of miR-25 was downregulated after H/R and high
mobility group box 1 (HMGB1) expression was increased. We also found that the
overexpression of miR-25 under conditions of H/R inhibited fibrosis and cell
apoptosis as well as reversing the cell cycle blocking. Additionally, the
targeting of HMGB1 by miR-25 was confirmed by a dual-luciferase reporter gene
assay. Moreover, the effects of miR-25 were further enhanced by a transforming
growth factor-beta1 (TGF-beta1)/Smad3 inhibitor, SB431542, as fibrosis was
reduced and apoptosis was suppressed. In conclusion, the protective effects of
miR-25 against H/R-induced fibrosis and apoptosis H9c2 cells were due to direct
targeting of HMGB1 through the downregulation of the TGF-beta1/Smad3 signaling
pathway.
PMID- 27513216
TI - Iron complexes of a bidentate picolyl-NHC ligand: synthesis, structure and
reactivity.
AB - The synthesis, structure and reactivity of bidentate picolyl N-heterocyclic
carbene (NHC) iron compounds were studied. Compounds [FeBr(HL)2]Br (1),
[FeBr(HL)(HMDS)] (2) and [FeBr2(HL)] (3) (HL = 1-mesityl-3-(pyridin-2
ylmethyl)imidazol-1-ylidene, HMDS = hexamethyldisilazide) were prepared from
H2LBr with suitable amounts of Fe(HMDS)2 or in situ prepared [Fe(HMDS)Br]. The
deprotonation of 1 with 2 eq. of LiHMDS gave [FeL2] (4), featuring dearomatized
pyridine moieties with exocyclic C-C double bonds. The protonation of 4 with 2
eq. of PPh3.HBr results in the formation of 1. Attempted deprotonation of 3 using
benzyl Grignard as the base resulted in transmetalation products [FeBnBr(HL)] (5)
and [FeBn2(HL)] (6). Exposure of 6 to CO resulted in the formation of diamagnetic
compound [Fe(CO)3(HL)] (7) and dibenzyl ketone. Prolonged exposure of 7 to CO
with heating induces pyridine dissociation, affording [Fe(CO)4(HL-kappaC)] (8).
Treatment of compound 6 with an equimolar amount of p-methoxybenzyl bromide
yielded homo- and cross-coupling products.
PMID- 27513217
TI - The Dilemma of Blood Transfusion: Strict or Liberal?
PMID- 27513218
TI - Porous Materials with Tunable Structure and Mechanical Properties via Templated
Layer-by-Layer Assembly.
AB - The deposition of stiff and strong coatings onto porous templates offers a novel
strategy for fabricating macroscale materials with controlled architectures at
the micro- and nanoscale. Here, layer-by-layer assembly is utilized to fabricate
nanocomposite-coated foams with highly customizable properties by depositing
polymer-nanoclay coatings onto open-cell foam templates. The compressive
mechanical behavior of these materials evolves in a predictable manner that is
qualitatively captured by scaling laws for the mechanical properties of cellular
materials. The observed and predicted properties span a remarkable range of
density-stiffness space, extending from regions of very soft elastomer foams to
very stiff, lightweight honeycomb and lattice materials.
PMID- 27513219
TI - MRI reconstruction with joint global regularization and transform learning.
AB - Sparsity based regularization has been a popular approach to remedy the
measurement scarcity in image reconstruction. Recently, sparsifying transforms
learned from image patches have been utilized as an effective regularizer for the
Magnetic Resonance Imaging (MRI) reconstruction. Here, we infuse additional
global regularization terms to the patch-based transform learning. We develop an
algorithm to solve the resulting novel cost function, which includes both
patchwise and global regularization terms. Extensive simulation results indicate
that the introduced mixed approach has improved MRI reconstruction performance,
when compared to the algorithms which use either of the patchwise transform
learning or global regularization terms alone.
PMID- 27513220
TI - Behavioral patterns of environmental performance evaluation programs.
AB - During the past decades numerous environmental performance evaluation programs
have been developed and implemented on different geographic scales. This paper
develops a taxonomy of environmental management behavioral patterns in order to
provide a practical comparison tool for environmental performance evaluation
programs. Ten such programs purposively selected are mapped against the
identified four behavioral patterns in the form of diagnosis, negotiation,
learning, and socialization and learning. Overall, we found that schemes which
serve to diagnose environmental abnormalities are mainly externally imposed and
have been developed as a result of technical debates concerning data sources,
methodology and ranking criteria. Learning oriented scheme is featured by
processes through which free exchange of ideas, mutual and adaptive learning can
occur. Scheme developed by higher authority for influencing behaviors of lower
levels of government has been adopted by the evaluated to signal their excellent
environmental performance. The socializing and learning classified evaluation
schemes have incorporated dialogue, participation, and capacity building in
program design. In conclusion we consider the 'fitness for purpose' of the
various schemes, the merits of our analytical model and the future possibilities
of fostering capacity building in the realm of wicked environmental challenges.
PMID- 27513221
TI - Effects of diazinon on adaptation to sea-water by the endangered Persian
sturgeon, Acipenser persicus, fingerlings.
AB - To replenish the depleting populations of sturgeon fishes especially Persian
sturgeon, Acipenser persicus in the Caspian Sea, millions of Persian sturgeon
fingerlings are farmed through artificial propagation and released into the
Iranian river estuaries annually. Fish osmoregulation is a vital physiological
process that can be affected during the release. Many Iranian river estuaries are
under the influence of pesticides originating from farming activities that may
affect osmoregulation. In this study, Persian sturgeon fingerlings were exposed
to sublethal concentrations (0, 0.18, 0.54, 0.9mgL(-)(1)) of diazinon for 96h
(short-term trial) and 12 days (long-term trial) in fresh water (FW) and then
fish were exposed in brackish water (BW) for 24h. After 96h and 12 days of
exposure in FW, the lower levels of plasma triidothyronine (T3), thyroxine (T4),
Na(+), Cl(-), K(+), gill Na(+)/K(+)- ATPase activity and number of chloride cells
were observed in exposed fish (0.54 and 0.9mgL(-)(1) diazinon) compared to
control group and 0.18mgL(-)(1) diazinon treatment. Also, higher levels of plasma
cortisol (except 0.18mgL(-)(1) diazinon treatment in long-term trial) were
observed in diazinon exposed fish compared to control group. However, gill
Na(+)/K(+)-ATPase activity and the number of chloride cells were higher in
fingerlings exposed to diazinon compared than control. When fish were exposed in
BW for 24h, the following changes occurred: (a) in short-term trial: increases in
cortisol and Cl(-) levels (0.54mgL(-)(1) diazinon ), Na(+) (0.9mgL(-)(1) diazinon
) and gill Na(+)/K(+)-ATPase activity (0.18mgL(-)(1) diazinon ). In control
group, cortisol, T4, Na(+), gill Na(+)/K(+)-ATPase activity and the number of
chloride cells increased significantly. (b) In long-term trial: increases in K(+)
levels in fish exposed to 0.9mgL(-)(1) diazinon, Na+ in all diazinon
concentrations and decreases in chloride cells number in fish exposed to 0.18mgL(
)(1) diazinon. In control group, significant increases were observed in cortisol,
T3, Na(+) and chloride cells number. Finally, gill showed many histopathological
damages during exposure in FW and BW. Our results suggest that the contamination
of river estuaries with diazinon may alter the osmoregulation ability of released
Persian sturgeon fingerlings, which could lead to a failure in their restocking
program in the Caspian Sea.
PMID- 27513222
TI - Development, validation, and application of a method for selected avermectin
determination in rural waters using high performance liquid chromatography and
fluorescence detection.
AB - Avermectins (AVM) are macrocyclic lactones used in livestock and agriculture. A
quantitative method of high performance liquid chromatography with fluorescence
detection for the determination of eprinomectin, abamectin, doramectin and
ivermectin in rural water samples was developed and validated. The method was
employed to study samples collected in the Pito Aceso River microbasin, located
in the Bom Jardim municipality, Rio de Janeiro State, Brazil. Samples were
extracted by solid phase extraction using a polymeric stationary phase, the
eluted fraction was re-concentrated under a gentle N2 flow and derivatized to
allow AVM determination using liquid chromatography with fluorescence detection.
The excitation and emission wavelengths of the derivatives were 365 and 470nm,
respectively, and a total chromatographic run of 12min was achieved. Very low
limits of quantification (22-58ngL(-1)) were found after re-concentration using
N2. Recovery values varied from 85.7% to 119.2% with standard deviations between
1.2% and 10.2%. The validated method was applied in the determination of AVM in
15 water samples collected in the Pito Aceso River microbasin, but most of them
were free of AVM or showed only trace levels of these compounds, except for a
sample that contained doramectin (9.11ugL(-1)). The method is suitable for
routine analysis with satisfactory recovery, sensitivity, and selectivity.
PMID- 27513223
TI - Comparison of the Tolerability of Diclofenac and Nepafenac.
AB - PURPOSE: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used
for the prevention and treatment of inflammation and pain following cataract
surgery. Preservative-free diclofenac and nepafenac drops are commonly used
ophthalmic NSAIDs. The purpose of this study was to compare the tolerability of
diclofenac to that of nepafenac. METHODS: In this prospective patient-blinded
study, consecutive patients undergoing cataract surgery were included. One drop
of nepafenac 0.1% and diclofenac sodium 0.1% were instilled in the right and left
eyes, respectively, one immediately after the other, 1 day before surgery. Visual
analog scale (scale 0-10) was used to measure patient discomfort, itching,
burning, and pain at 1 second (s), 15 s, 1 minute (min), and 5 min
postadministration. RESULTS: Overall, 44 eyes of 22 patients were included in
this study. Diclofenac and nepafenac had high and similar tolerability at all
time points with no significant difference regarding all aspects of tolerability.
A vast majority of patients (72%) did not prefer 1 drop over the other in terms
of overall comfort. CONCLUSIONS: Both diclofenac and nepafenac seem to have
similar high tolerability. Diclofenac may be an affordable alternative to
nepafenac and therefore should be considered by prescribing physicians,
specifically in preoperative cataract patients.
PMID- 27513224
TI - CT Radiation Dose Reduction in Robot-assisted Pediatric Spinal Surgery.
AB - STUDY DESIGN: Retrospective consecutive cohort series. OBJECTIVE: The aim of this
study was to develop a low-dose computed tomography (CT) protocol for use in
robot-assisted pediatric spinal surgery. SUMMARY OF BACKGROUND DATA: CT scans are
utilized preoperatively for preoperative planning, by navigation software during
robot-assisted surgery, and postoperatively to assess surgical implant placement.
Traditionally high radiation doses produced by CT scanning are a concern in the
highly radiosensitive pediatric population. METHODS: We developed a low-dose
protocol using phantom scans. A cohort of patients undergoing CT scanning using
the low-dose protocol was collected. Further, a matching cohort of patients who
underwent standard scanning was collected. Image quality was assessed by observer
ratings. Radiation doses and image quality metrics were compared for the standard
and low-dose protocol patients. RESULTS: Effective dose significantly decreased
84% to 91% depending on patient size and whether the scan was preoperative or
postoperative. All scans were compatible with the navigation software. No
clinically significant differences in image quality were observed between low
dose and standard patient cohorts. CONCLUSIONS: Task-based CT protocol
optimization can produce acceptable image quality with dose comparable to
standard two-view radiography. LEVEL OF EVIDENCE: 2.
PMID- 27513225
TI - Prospective Comparison of Age- and Sex-related Differences in Quantifiable 10-S
Grip and Release and 10-S Step Test Results for Diagnosis of Cervical Spondylotic
Myelopathy in 454 Patients With Cervical Spondylotic Myelopathy and 818
Asymptomatic Subjects.
AB - STUDY DESIGN: A prospective comparison. OBJECTIVE: The purpose of this
prospective study was to verify the clinical effectiveness of the 10-s grip and
release (G&R) and 10-s step quantitative tests for assessing the severity of
cervical spondylotic myelopathy (CSM) and to compare age- and sex-related
differences in the results between large cohorts of CSM patients and asymptomatic
subjects. SUMMARY OF BACKGROUND DATA: To determine the severity of CSM, objective
and reproducible means of measuring patient disability are essential. No studies
have evaluated differences in quantitative test results between a large series of
CSM patients and healthy subjects. METHODS: Four hundred fifty-four CSM patients
and 818 asymptomatic subjects were included. The Japanese subjects were in their
40s to 70s and were divided according to their age by decade. The 10-s G&R and 10
s step tests were used to quantitatively assess performance. The severity of
myelopathy before surgery was evaluated according to a scoring system proposed by
the Japanese Orthopaedic Association for cervical myelopathy (JOA score) in the
CSM patients. RESULTS: In the CSM patients, the 10-s G&R and step test results
significantly correlated with the JOA score (P < 0.0001). The number of the 10-s
G&R and step tests significantly decreased with age in both groups. There was a
difference in the 10-s G&R and step test results between males and females. In
the asymptomatic subjects, the number of the 10-s G&R and step tests in the
females was less than that in the males. The numbers in the 10-s G&R and step
tests were significantly lower in CSM patients than those in asymptomatic
subjects in each decade (P < 0.01). CONCLUSION: The 10-s G&R and 10-s step tests
were useful for quantitatively assessing CSM severity, and age and sex
differences in results should be considered in screening. LEVEL OF EVIDENCE: 2.
PMID- 27513226
TI - How Reliable Are the Reported Genetic Associations in Disc Degeneration?: The
Influence of Phenotypes, Age, Population Size, and Inclusion Sequence in 809
Patients.
AB - STUDY DESIGN: Prospective genetic association study. OBJECTIVE: The aim of this
study was to document the variations in the genetic associations, when different
magnetic resonance imaging (MRI) phenotypes, age stratification, cohort size, and
sequence of cohort inclusion are varied in the same study population. SUMMARY OF
BACKGROUND DATA: Genetic associations with disc degeneration have shown high
inconsistency, generally attributed to hereditary factors and ethnic variations.
However, the effect of different phenotypes, size of the study population, age of
the cohort, etc have not been documented clearly. METHODS: Seventy-one single
nucleotide polymorphisms (SNPs) of 41 candidate genes were correlated to six MRI
markers of disc degeneration (annular tears, Pfirmann grading, Schmorl nodes,
Modic changes, Total Endplate Damage score, and disc bulge) in 809 patients with
back pain and/or sciatica. In the same study group, the correlations were then
retested for different age groups, different sample, size and sequence of subject
inclusion (first 404 and the second 405) and the differences documented. RESULTS:
The mean age of population (M: 455, F: 354) was 36.7 +/- 10.8 years. Different
genetic associations were found with different phenotypes: disc bulge with three
SNPs of CILP; annular tears with rs2249350 of ADAMTS5 and rs11247361 IGF1R; modic
changes with VDR and MMP20; Pfirmann grading with three SNPs of MMP20 and Schmorl
node with SNPs of CALM1 and FN1 and none with Total End Plate Score.Subgroup
analysis based on three age groups and dividing the total population into two
groups also completely changed the associations for all the six radiographic
parameters. CONCLUSION: In the same study population, SNP associations completely
change with different phenotypes. Variations in age, inclusion sequence, and
sample size resulted in change of genetic associations. Our study questions the
validity of previous studies and necessitates the need for standardizing the
description of disc degeneration, phenotype selection, study sample size, age,
and other variables in future studies. LEVEL OF EVIDENCE: 4.
PMID- 27513227
TI - Comparing National Inpatient Sample and National Surgical Quality Improvement
Program: An Independent Risk Factor Analysis for Risk Stratification in Anterior
Cervical Discectomy and Fusion.
AB - STUDY DESIGN: Retrospective study of prospectively collected data. OBJECTIVE: To
explore interdatabase reliability between National Inpatient Sample (NIS) and
National Surgical Quality Improvement Program (NSQIP) for anterior cervical
discectomy and fusion (ACDF) in data collection and its impact on subsequent
statistical analyses. SUMMARY OF BACKGROUND DATA: Clinical studies in orthopedics
using national databases are ubiquitous, but analytical differences across
databases are largely unexplored. METHODS: A retrospective cohort study of
patients undergoing ACDF surgery was performed in NIS and NSQIP. Key demographic
variables, comorbidities, intraoperative characteristics, and postoperative
complications were analyzed via bivariate and multivariate analyses. RESULTS: A
total of 112,162 patients were identified from NIS and 10,617 from NSQIP.
Bivariate analysis revealed small, but significant, differences between patient
demographics, whereas patient comorbidities and ACDF intraoperative variables
were largely much more distinct across the two databases. Multivariate analysis
identified independent risk factors between NIS and NSQIP for mortality, cardiac
complications, and postoperative sepsis, some of which were identified in both
but most of which were unique to one database. Identification of independent risk
factors from both databases specifically highlights their greater validity and
importance in stratifying patient risks. In addition, NSQIP was found to be a
more accurate predictor for complications based on the average areas under the
receiver-operating curve (CNSQIP = 0.83 vs. CNIS = 0.81) across the multivariate
models. Complication rate analysis between inpatient and outpatient settings in
NSQIP showed the importance of at least 30-day patient follow up, which was
devoid in NIS data tabulation and further marked its weakness compared with
NSQIP. CONCLUSION: Despite having largely similar patient demographics, this
study highlights critical risk factors for ACDF and demonstrates how different
patient profiles can be across NIS and NSQIP, the impact of such differences on
identification of independent risk factors, and how NSQIP is ultimately better
suited for adverse-event studies. LEVEL OF EVIDENCE: 3.
PMID- 27513228
TI - Seroprevalence of measles, mumps, rubella, and varicella amongphysicians and
nurses in Jordan.
AB - BACKGROUND/AIM: Measles, mumps, rubella, and varicella can affect susceptible
healthcare workers who might subsequently spread the infection to susceptible
patients and workers. Here, we aim to determine the seroprevalence of these
infections among physicians and nurses and to compare the history of varicella
with the results of varicella antibodies among study participants. MATERIALS AND
METHODS: Two randomly selected groups, one group of physicians and one of nurses,
from a university hospital in Jordan were interviewed and their serum IgG
antibodies were measured. RESULTS: The physicians and nurses group had 252 and
241 participants, respectively. The physicians group had significantly more males
and younger participants. The percentage of individuals in the physician and
nurse groups with positive antibodies to measles was 75.4% and 75.1%,
respectively; mumps, 88.5% and 94.2%; rubella, 89.3% and 87.1%; and varicella,
92.1% and 92.5%. Immunity was similar between the 2 groups except for mumps,
where significantly more nurses were immune. The positive and negative predictive
values for the history of varicella to predict immunity in all participants were
95% and 13.5%, respectively. CONCLUSION: A small but important proportion of our
healthcare workers are still susceptible to measles, mumps, rubella, and
varicella. In addition, the recall history to varicella showed suboptimal ability
to predict immunity.
PMID- 27513229
TI - Evaluation of tetanus antibody levels in adults in Yozgat, Turkey.
AB - BACKGROUND/AIM: To assess the immune status against tetanus in relation to self
declared vaccination status among an adult population in Yozgat, Turkey. METHODS:
Questionnaires and blood specimens were collected from 267 individuals over 18
years of age in Yozgat, Turkey. Antitetanus antibodies were determined
quantitatively by enzyme-linked immunosorbent assay. RESULTS: Among the 267
subjects (mean age 43.4 +/- 15.6; male:female, 133:134) 168 (62.9%) had
protective level of tetanus antibody titers. There was a characteristic
distribution of the tetanus antibody titers in different age groups as it dropped
with increasing age. Protective immunity was obtained in 74.1% of urban and 47.9%
of rural participants. The lowest immunity was observed among farmers (53.3%) and
housewives (55.6%) when compared to other occupations. Protective antibody titers
were detected in 25% of the individuals who had not finished any school, while
the rate was 83.7% in those who had graduated from university. While the
protection rate in women who had been vaccinated during pregnancy was 78.3%, this
rate was 39.2% in nonvaccinated women. CONCLUSION: Our findings confirm that only
62.9% of the population is immunized against tetanus, with a lack of coverage in
particular for the elderly and in rural areas. It is necessary to follow the
recommendations for 10-year boosters for tetanus.
PMID- 27513230
TI - Oxidative stress-induced DNA damage and homocysteine accumulation may beinvolved
in ovarian cancer progression in both young and old patients.
AB - BACKGROUND/AIM: Biochemical, environmental, and genetic factors such as oxidative
stress-induced DNA damage and homocysteine (Hcy) accumulation in the blood are
involved in the development and progression of ovarian cancer. This study
measured some biomarkers closely linked to the progression of ovarian cancer and
also found their correlates. MATERIALS AND METHODS: Thirty patients were
diagnosed with ovarian cancer using pelvic examination, transvaginal ultrasound,
and cancer antibody (CA-125) measurement. Total oxidative stress (TOS), DNA
damage, Hcy, malondialdehyde (MDA), total antioxidant status (TAS), and other
biochemical parameters were determined. RESULTS: TOS and DNA damage were
positively and significantly correlated between themselves and were involved in
causation of tumors as reflected by significantly (P < 0.001) higher CA-125,
erythrocyte sedimentation rate (ESR), creatinine, and C-reactive protein (CRP) in
both young and old patients. Both were significantly correlated with Hcy, LDL
cholesterol, alanine aminotransferase, aspartate aminotransferase, CRP, MDA, and
CA-125. However, they were negatively correlated with TAS. Thus, excessive
inflammation and oxidative stress caused an increase in DNA damage and enhanced
Hcy content, leading to development of ovarian cancer. CONCLUSION: This study
suggests the use of antioxidants as drugs to reduce oxidative stress, DNA damage,
and other causes of cancer development.
PMID- 27513231
TI - Correlation between HFE gene polymorphisms and increased risk of coronary artery
disease among patients with type 2 diabetes in Iran.
AB - BACKGROUND/AIM: Diabetes mellitus is a risk factor for cardiovascular diseases
(CVDs), which are among the major causes of deaths in type 2 diabetes (T2D). The
purpose of the present study was to determine the association of C282Y and H63D
mutations in the HFE gene with increased risk of coronary artery disease (CAD) in
T2D patients. MATERIALS AND METHODS: Two hundred and ninety individuals were
divided into two groups: a case group and a control group. Genomic DNA of
peripheral venous blood cells was extracted and the HFE gene mutations were
analyzed using the PCR-RFLP technique. RESULTS: Data analysis revealed a
significant difference between the allele frequencies of H63D and C282Y mutations
between the case group and the controls (P < 0.05). The relationships between the
GA and GG genotypes in C282Y and H63D mutations in terms of fasting blood sugar
(FBS), lipid profile (total cholesterol, triglycerides, high-density lipoproteins
(HDL), low-density lipoproteins), body mass index (BMI), HbA1c, micro
albuminuria, and creatine levels did not show a significant differences between
the two groups (P > 0.05). Using a logistic regression model, BMI, FBS, HDL, and
total cholesterol levels were significantly different with independent predictors
of CVD (P < 0.05). CONCLUSION: Our results revealed a significant correlation
between C282Y and H63D mutations and the development of CAD in T2D patients.
PMID- 27513232
TI - Clinical outcomes and optical performance of four differentmultifocal intraocular
lenses.
AB - BACKGROUND/AIM: The purpose of the present study was to evaluate clinical
outcomes and optical performance of 4 different multifocal intraocular lenses
(IOLs). MATERIALS AND METHODS: Ninety eyes of 51 patients who received Reviol MFM
611, Reviol MFM 625, Acri.LISA, and ReSTOR SN6AD3 multifocal IOLs after cataract
surgery were retrospectively evaluated. The patients were similar in terms of
age, sex, cataract hardness and axial length. The mean outcome measures were
uncorrected and corrected distance visual acuity (UDVA, CDVA), distance-corrected
intermediate and near visual acuity (DCIVA, DCNVA), intra or postoperative
complications, and contrast sensitivity (CS) results under mesopic conditions.
The mean follow up period was 10.5 months (range: 6-12 months). RESULTS: All
cases were within +/- 0.75 D of emmetropia. Postoperative increase in UDVA and
DCNVA was statistically significant in all groups. The Acri.LISA group showed
slightly lower DCIVA compared with the other IOLs. CS was clinically similar
between the groups. None of the patients developed any early or late
postoperative complication or neuroadaptation problem, which necessitated
explantation of the lens. CONCLUSION: All four multifocal lens designs provided
satisfactory visual functions and CS results in patients who fulfilled the
criteria for multifocal lens implantation.
PMID- 27513233
TI - The utility of the TIMI risk index on admission for predicting angiographic no
reflow after primary percutaneous coronary intervention in patients with STEMI.
AB - BACKGROUND/AIM: The thrombolysis in myocardial infarction (TIMI) risk score
(TRS), and the TIMI risk index (TRI) have been reported in coronary artery
disease patients. We investigated whether admission TRI is associated with no
reflow (NRF) in patients undergoing primary percutaneous coronary intervention (p
PCI). MATERIALS AND METHODS: ST-segment elevation myocardial infarction (STEMI)
patients treated with p-PCI were included in the study. TRI was calculated on
admission using specified variables. We defined the angiographic NRF phenomenon
as a coronary TIMI flow grade of <=2 after the vessel was recanalized or a TIMI
flow grade of 3 together with a final myocardial blush grade (MBG) of <2 in a
manner as described in previous studies. RESULTS: A total of 371 patients (aged
62 +/- 14 years; 73/27 men to women ratio) who underwent p-PCI were enrolled in
the study. In terms of age, NRF patients were older than reflow patients (P <
0.017 for MBG). Killip class III-IV designations were more common in NRF patients
(P = 0.029 for MBG). TRI (P = 0.014 for MBG) values were significantly greater in
the NRF group. TRI was an independent predictor of NRF according to MBG flow (P =
0.003, B = -0.035, Exp B = 0966, 95% CI, 0.944-0.988). CONCLUSION: Admission TRI
may predict the development of NRF phenomenon after p-PCI in patients with acute
STEMI.
PMID- 27513234
TI - Effectiveness of P6 acupoint electrical stimulation in preventing
postoperativenausea and vomiting following laparoscopic surgery.
AB - BACKGROUND/AIM: The effects of pericardium 6 (P6) electrical stimulation in
patients at risk of postoperative nausea and vomiting (PONV) following
laparoscopic surgery were evaluated. MATERIALS AND METHODS: Eighty patients for
laparoscopic surgery with at least one of the determined risks (nonsmoker,
female, previous PONV/motion sickness, or postoperative opioid use) were
randomized into either an active or sham group. At the end of surgery, Reletex
electrical acustimulation was placed at the P6 acupoint. The active group had
grade 3 strength and the sham group had inactivated electrodes covered by
silicone. It was worn for 24 h following surgery. PONV scores were recorded.
RESULTS: The active group had significantly shorter durations of surgery and
lower PONV incidence over 24 h (35.1% versus 64.9%, P = 0.024) and this was
attributed to the lower incidence of nausea (31.4% versus 68.6%, P = 0.006). The
overall incidence of vomiting was not significantly different between the groups,
but it was higher in the sham group of patients with PONV risk score 3 (23.9%, P
= 0.049). CONCLUSION: In patients at high risk for PONV, P6 acupoint electrical
stimulation lowers the PONV incidence by reducing the nausea component. However,
this reduction in nausea is not related to increasing PONV risk scores.
PMID- 27513235
TI - Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and
prostate cancer risk and aggressiveness in Bulgarian patients.
AB - BACKGROUND/AIM: The aim of our study was to elucidate the role of polymorphisms
in AR, CYP1B1, CYP19, and SRD5A2 genes for prostate cancer (PC) development in
Bulgarian patients. MATERIALS AND METHODS: We genotyped 246 PC patients and 261
controls (155 with benign prostate hyperplasia and 107 healthy population
controls) using direct sequencing, PCR-RFLP, SSCP, and fragment analysis.
RESULTS: The allele and genotype frequencies of most of the studied variants did
not differ significantly between cases and controls. Increased frequencies of the
C/C genotype and C allele of rs1056837 in CYP1B1, and genotype 7/8 of the (TTTA)n
repeat polymorphism in CYP19, were observed in patients in comparison with
controls.The 8/9 and the 7/12 genotypes of (TTTA)n in CYP19 showed suggestive
evidence for association with decreased prostate cancer risk and the risk for
aggressive disease, respectively. The haplotype analysis revealed 2 CYP1B1
haplotypes associated with PC risk reduction. CONCLUSION: Some CYP1B1 haplotypes
and genotypes of the CYP19 (TTTA)n repeat appeared to be associated with disease
risk or aggressiveness in Bulgarian PC patients. In contrast, the SRD5A2
polymorphisms (V89L and (TA)n repeat), the CAG repeat in AR, and the Arg264Cys
variant in CYP19A1 are most likely not implicated in prostate carcinogenesis.
PMID- 27513236
TI - The relationship of breast arterial calcification detected in mammographic
examinations with cardiovascular diseases, cardiovascular risk factors, parity,
and breastfeeding.
AB - BACKGROUND/AIM: We aimed to detect the incidence of breast arterial calcification
(BAC) in patients that underwent mammography and to reveal the relationship of
BAC with cardiovascular diseases, cardiovascular risk factors, parity, and
breastfeeding. MATERIALS AND METHODS: A total of 1195 female patients were
included in this study. Cases that were positive for BAC during mammography were
recorded. The relationship of BAC with age, body mass index, parity,
breastfeeding, menopause, smoking, alcohol consumption, oral contraceptive use,
hormone replacement therapy, and histories of hypertension (HT), diabetes
mellitus (DM), coronary artery disease (CAD), and cerebral vascular diseases were
investigated. RESULTS: Overall, 97 of 1195 cases were positive for BAC. In
univariate analysis, age, educational status, parity, breastfeeding, menopause,
hyperlipidemia, and DM, HT, and CAD histories were found to be separate risk
factors that had an effect on the development of BAC. The effects of age, parity,
and breastfeeding history were maintained in the logistic regression analysis (P
= 0.001, P = 0.001, P = 0.024, respectively; P < 0.05 was significant), while the
significance of the other analyzed variables was lost (P > 0.05). CONCLUSION: We
found that BAC is associated with age, parity, and breastfeeding but not with
cardiovascular diseases and cardiovascular risk factors.
PMID- 27513237
TI - Celiac disease in children with chronic constipation.
AB - BACKGROUND/AIM: Chronic constipation (CC) and celiac disease (CD) are the most
common conditions encountered in pediatric gastroenterology. The association of
these two disorders has not been evaluated properly. We analyzed the prevalence
and outcome of CD in children with CC. MATERIALS AND METHODS: The study included
children with CC (n = 313) and healthy children (n = 990). Serum IgA and IgA
antitissue transglutaminase antibodies (IgA-tTG) were studied in all subjects.
Intestinal biopsy and HLA-DQ2/DQ8 typing was performed in subjects with elevated
IgA-tTG. RESULTS: Serology was positive in 8 children (2.5%) with CC and 6
children (0.6%) from the control group (P < 0.05). Histopathological examination
revealed total villous atrophy in two subjects in the control group. Other
subjects had Marsh 0-1 lesions. All patients with CC and 4 children from the
control group were classified as having potential CD. Two children in the control
group had silent CD. Spontaneous loss of serum tTG-IgA occured in 75% of the
subjects with potential CD at the end of the 1st year. CONCLUSION: Our study
revealed that serological evaluation CD may be omitted in children with CC at
initial examination. It may be perform in selected patients such as those
associated with prolonged symptoms or malnutrition.
PMID- 27513238
TI - The antioxidant and antimutagenic activities of Ankaferd blood stopper,a natural
hemostatic agent used in dentistry.
AB - BACKGROUND/AIM: This study investigated the antioxidant and antimutagenic
properties of Ankaferd blood stopper (ABS), a plant-based topical hemostatic
agent used in Turkey to treat external hemorrhages and bleeding during dental
surgery. While previous studies have examined the antimicrobial,
antiinflammatory, and anticarcinogenic properties of ABS, to our knowledge, this
is the first study to report on the antioxidant and antimutagenic activities of
this drug. MATERIALS AND METHODS: Antioxidant activity was evaluated using DPPH
radical-scavenging and beta-carotene-linoleic acid tests. Antimutagenic activity
was assessed using the Ames Salmonella/microsome mutagenicity test with the
bacterial mutant strains Salmonella typhimurium TA98 and TA100. RESULTS: Although
ABS demonstrated no free-radical-scavenging activity in DPPH assays at the tested
concentrations, beta-carotene-linoleic acid testing found ABS to have a total
antioxidant activity rate of 47.06 +/- 4.41%. Antimutagenic effects were observed
on TA100 at plate concentrations of 5%, 0.5%, and 0.05%, and on TA98 only at a
plate concentration of 5%. CONCLUSION: ABS was shown to possess antioxidant and
antimutagenic properties that could be of potential value in the fields of
medicine and dentistry.
PMID- 27513239
TI - Treatment of mixed astigmatism: early clinical outcomes withWaveLight and
Technolas excimer lasers.
AB - BACKGROUND/AIM: We aimed to compare the results of WaveLight Allegretto Wave Eye
Q 400 Hz and Technolas 217z100 excimer lasers in the treatment of mixed
astigmatism. MATERIALS AND METHODS: Forty-nine patients who underwent laser in
situ keratomileusis for mixed astigmatism were included in this retrospective
study. Twenty-eight eyes of 21 patients were treated with WaveLight and 46 eyes
of 28 patients were treated with the Technolas excimer laser. The patients'
visual acuities and refractive values were evaluated on postoperative day 1 and
at 1 and 3 months. RESULTS: In the WaveLight and Technolas groups, cylindrical
refractive errors at month 3 were -0.92 +/- 0.28 D and -0.88 +/- 0.46 D,
respectively. Spherical equivalent values for the groups at month 3 were -0.38 +/
0.73 D and -0.33 +/- 0.20 D, respectively. There was no significant difference
in postoperative uncorrected distance visual acuity at month 3 between the two
groups (P = 0.671). At postoperative month 3, 70% of patients treated with
WaveLight and 100% of patients treated with Technolas had an uncorrected distance
visual acuity of 20/25 or better (P = 0.211). CONCLUSION: There were no
significant differences in refraction and visual acuity between the WaveLight and
Technolas groups during a 3-month follow-up period after laser in situ
keratomileusis for mixed astigmatism.
PMID- 27513240
TI - eNOS gene polymorphisms in paraffin-embedded tissues of prostate cancer patients.
AB - BACKGROUND/AIM: The purpose of the present study was to investigate whether
endothelial nitric oxide synthase (eNOS) gene polymorphisms play a role in
prostate cancer (PCa). MATERIALS AND METHODS: We examined three eNOS gene
polymorphisms (T-786C promoter region, G894T, and Intron 4 VNTR 4a/b) at
extracted DNAs from 50 formalin-fixed paraffin-embedded tissues of PCa patients.
For the controls, blood samples obtained from 50 healthy men were studied.
Genotyping of molecular variants was performed by PCR-RFLP technique. RESULTS: We
found that the TC genotype of the T-786C polymorphism was associated with PCa
risk (OR: 3.325, CI: 1.350-8.188, P = 0.008). The eNOS G894T polymorphism was
also associated with PCa. The frequency of the 894T allele was significantly
higher in PCa patients. No association was identified between intron 4 VNTR
polymorphism and PCa. CONCLUSION: We found significant differences in genotypic
and allelic frequencies between PCa patients and controls for eNOS T-786C and
G894T polymorphisms. The presence of the T-786C genotype and 894T allele in
carriers increased the risk of PCa. No association was found between intron 4
VNTR polymorphism and PCa patients.
PMID- 27513241
TI - Effects of blood pressure and sex on heart-vessel coupling in essential
hypertension.
AB - BACKGROUND/AIM: This study aimed to investigate the impact of blood pressure and
sex on heart-vessel coupling in patients with essential hypertension via
ultrasound. MATERIALS AND METHODS: We studied 76 patients with essential
hypertension (48 males and 28 females) and 65 healthy controls (33 males and 32
females). Coupling parameters were obtained using ultrasound technology combined
with brachial artery blood pressure measurement. RESULTS: The Ea and Ees were
higher in the hypertension group than in the control group (P < 0.01), with no
statistically significant difference in Ea/Ees between the two groups (P >0.05).
After subjects were classified by sex, the Ea and Ees of males and females in the
hypertension group were higher than those in the control group (P < 0.05 or P <
0.01), while the Ea/Ees was lower in hypertensive females than in control females
(P < 0.05). CONCLUSION: In female patients with essential hypertension, heart
vessel coupling was easily damaged, and systolic blood pressure was associated
with heart-vessel coupling damage to some extent.
PMID- 27513242
TI - Categorization of ureteroscopy complications and investigation of associated
factors by using the modified Clavien classification system.
AB - BACKGROUND/AIM: The purpose of the present study was to review the complications
of ureteroscopy (URS) by using the modified Clavien classification system (MCCS)
and to investigate the factors associated with complications. MATERIALS AND
METHODS: Data regarding 811 patients who underwent URS for ureteral calculus were
analyzed. Peroperative and postoperative complications were recorded. The
patients were divided into seven groups depending on the severity of the
complications. The association of sex, stone size, number, and localization with
each MCCS grade was also evaluated. RESULTS: The average age was 45 years. The
success of the procedure after one session was 93.5%. Complications were recorded
in 57.9% of the patients. According to the MCCS, grade I, II, IIIa, IIIb, IVa,
IVb, and V complications were documented in 29.8%, 7.1%, 8.6%, 11%, 0%, 1.2%, and
0% of the patients, respectively. The factors associated with the complications
graded by MCCS were sex, stone size, number of stones, and localization. In
addition, in multivariate analysis, history of previous surgeries for
urolithiasis, orifice dilatation, and instrument size were associated with
complications. CONCLUSION: According to MCCS, sex, history of previous surgeries
for urolithiasis, orifice dilatation, size of the instrument, stone size, number
of stones, and localization are associated with different grades of complications
in URS.
PMID- 27513243
TI - Premenstrual syndrome and life quality in Turkish health science students.
AB - BACKGROUND/AIM: The purpose of the present study was to investigate the incidence
of PMS, risk factors affecting PMS symptoms, and life quality in health science
students. MATERIALS AND METHODS: A total of 608 volunteer female students
studying at the health campus of a state university in Turkey were included in
the study. The participants were asked to fill out questionnaires on
sociodemographic data, PMS symptoms, and SF-36 life quality tests. RESULTS: The
overall frequency of PMS among participants was 84.5%. The average PMS and
general health SF scores were 118.34 +/- 37.3 and 20.03 +/- 3.72, respectively.
Students who had irregular breakfast, drank >=2 cups of coffee/day, and consumed
alcohol or fast food had higher PMS scores. Irregular menstruation and family
history increased PMS scores and decreased life quality (P < 0.05). The life
quality of the students significantly decreased as the severity of PMS increased
(P < 0.001). CONCLUSION: Low body mass index, family history, irregular
menstruation, bad eating habits such as fast food consumption and irregular
breakfasts, and coffee and alcohol consumption increased PMS risk significantly.
In order to improve their life quality, students should be informed about the
symptoms, risk factors, and management options of PMS.
PMID- 27513244
TI - Brachiobasilic arteriovenous fistula with transpositionof the basilic vein: a
multicenter study.
AB - BACKGROUND/AIM: The aim of this paper was to present our 3-year multicenter
experience in creating a vascular access using the basilic vein. The third choice
in creating vascular access is the brachiobasilic arteriovenous fistula (AVFs)
with transposition of the basilic vein. MATERIALS AND METHODS: During 2010-2012,
out of a total of 874 AVFs that were performed in our two centers, 54 were
brachiobasilic fistulas (6.71%), performed on 54 patients. All surgical
procedures were performed by two surgical teams, one for each center. There were
no significant differences regarding the patients' age, sex, and comorbidities
between the two centers. RESULTS: We reported a total of six postoperative
complications (11.10%): two wound infections, two arm edemas, one hematoma, and
one bleeding (due to a collateral ligature slippage), which required surgical
intervention the same day. None of the other complications required another
surgery. The first year patency rate was 89.79% (four fistulas failed due to
thrombosis and one due to perforation) and the second year patency rate was
62.12%. CONCLUSION: The brachiobasilic AVF with transposition of the basilic
vein, according to the latest guidelines, remains a well-documented and feasible
third option in creating vascular access with better results than graft fistulas.
PMID- 27513245
TI - Childhood acute lymphoblastic leukemia: refusal and abandonmentof treatment in
the southeast of Iran.
AB - BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) accounts for 25% of all
malignancies in children. ALL treatment has standard protocols, and treatment
abandonment is a main cause of treatment failure. Therefore, this study aimed to
assess the relationship between socioeconomic status and rate as well as cause of
abandoned treatment in children with ALL in the southeast of Iran. MATERIALS AND
METHODS: This retrospective, descriptive cohort study was conducted with ALL
patients at the Ali Asghar Hospital in the city of Zahedan. The study population
included 22 children with different subtypes of ALL who had abandoned their
treatment. A structural questionnaire was filled out by patients or their
parents. Results were assessed using descriptive and analytical tests. RESULTS:
The rate of treatment abandonment was 24.4% (22 patients).We had 18 ALL-L1
(78.3%) and four ALL-L2 (17.4%) patients. Reasons for treatment abandonment were
low family income, transportation difficulties, the father's education status,
conviction about ALL's incurability, and reference to spiritual means,
respectively. CONCLUSION: Low family income, transportation difficulties, the
father's education status, belief about ALL's incurability, and reference to
spiritual means were the most common associations with ALL treatment abandonment
in that order. Financial problems in this part of the country can impose high
costs to the healthcare system.
PMID- 27513246
TI - Evaluation of the relationship between migraine disorder andoral comorbidities:
multicenter randomized clinical trial.
AB - BACKGROUND/AIM: Although migraine is a common disorder, there is a lack of
research investigating the possible relationship between migraine and oral
health. The aim of the present study was to explore the relationship between
temporomandibular disorders, bruxism, dental caries, periodontal status, and
migraine disorder in a multicenter, parallel, case-controlled clinical study.
MATERIALS AND METHODS: A total of 2001 participants were divided into two groups:
migraineurs (nm = 998) and nonmigraineurs (nh = 1003). International Headache
Society's Second Edition of International Classification of Headache Disorders
and modified Migraine Disability Assessment surveys were administered to evaluate
the level of migraine; a pretreatment questionnaire and the World Health
Organization oral health assessment form were used to determine the oral
comorbidities and their possible effects on DMFT index, gingival plaque index,
existence of temporomandibular disorders, bruxism, and consistency of daily oral
hygiene habits. RESULTS: The mean age was 39.6 +/- 10.5 years. Female patients
seemed to experience migraine attacks more than male patients (64%). The
frequency of gastroesophageal reflux was higher in migraineurs in comparison with
nonmigraineurs (47%) and tooth wear and abrasion also seemed more frequent (76%).
DMFT and plaque index scores showed significant differences for both groups.
CONCLUSION: There is a strong relationship between migraine and oral health
status. The existence of reflux in addition to migraine leads to higher dental
problems.
PMID- 27513247
TI - Effects of a self-management educational program on metabolic control in type 2
diabetes.
AB - BACKGROUND/AIM: India has 63 million diabetic people and the overall prevalence
of diabetes in this country is 8.37%. Lifestyle modification by education is the
most cost-effective strategy to have better metabolic control. The aim of this
study was to investigate the effects of a self-management educational program on
control of type 2 diabetes. MATERIALS AND METHODS: It was a randomized controlled
interventional study conducted among 306 patients with type 2 diabetes mellitus
attending the Diabetic Clinic at G.T.B. Hospital, Delhi, from March 2010 to May
2013. The intervention was in the form of group education based on a self
management program, which was earlier developed in the pilot study. RESULTS: The
baseline characteristics were comparable in the two groups. After 6 months, there
was a significant improvement in the HbA1c levels (P = 0.0001), physical activity
level (P = 0.001), and BMI (P = 0.001) in the study group as compared to the
control group and this difference persisted even when analysis was done using
generalized estimation equations. CONCLUSION: The findings of this study proved
that a self-management educational program is an essential component in the
management of diabetes and provided concrete evidence that this is an effective
instrument in the control of body weight, blood pressure, and glycated Hb levels
in type 2 diabetes.
PMID- 27513248
TI - Evaluation of Borrelia burgdorferi sensu lato seroprevalencein the province of
Bolu, Turkey.
AB - BACKGROUND/AIM: The aim of the present study was to determine the seroprevalence
of Borrelia burgdorferi sensu lato in the city center and the province of Bolu,
Turkey. MATERIALS AND METHODS: A stratified sampling method was used to determine
the study population. A total of 196 blood samples were collected. A
questionnaire was completed by each participant in the study. ELISA was performed
and positive serologic results were confirmed using western blotting. Data were
analyzed statistically using the chi-square test. RESULTS: Seropositivity rates
of B. burgdorferi IgM and IgG were determined as 14.8% (29/196) and 13.7%
(27/196) respectively by ELISA. A total of nine serum samples (4.6%) were found
positive for IgG, and seven samples (3.8%) were positive for IgM according to
western blotting. Seropositivity rates were found to be higher in people living
in rural areas (11.1%), in women (8.3%), in people who were illiterate (10.0%),
in people engaged in agriculture (10.8%), and in the age group of 40-60 years
(10.0%). No statistically significant difference was found between seropositivity
rates and survey data. CONCLUSION: The seroprevalence of Lyme disease was
determined in our region. Detection of endemic regions of Lyme disease with
determination of seropositivity rates will increase the awareness among
clinicians about this disease.
PMID- 27513249
TI - Investigation of enteropathogenic Escherichia coli and Shiga toxin
producingEscherichia coli associated with hemolytic uremic syndrome in Izmir
Province, Turkey.
AB - BACKGROUND/AIM: The purpose of this study was to investigate Shiga toxin
producing Escherichia coli (STEC) and enteropathogenic Escherichia coli (EPEC)
strains originating from diarrheagenic patients. MATERIALS AND METHODS: A total
of 102 patients with diarrhea between October 2012 and January 2013 were enrolled
in this study. Multiplex and standard polymerase chain reactions were performed
to detect and distinguish STEC and EPEC strains. O serotyping of EPEC was carried
out by monovalent antisera. The O and H serotyping of STEC strains was performed
at the Refik Saydam Institute, Ankara. RESULTS: A total of 5 (3.42%) strains were
identified as STEC, and 3 strains (2.05%) were atypical EPEC. One of the STEC
serotypes was O157:H7 carrying VT1, Stx1A, and escv genes. The other STEC strain
was identified as O174:H21, which is associated with hemolytic uremic syndrome
and consists of VT2 and Stx2A genes. One of the EPEC and three of the STEC
serotypes were nontypeable. The serotypes of the atypical EPEC strains were
identified as O114 and O26. CONCLUSION: To the best of our knowledge, this is the
first report of O174:H21 from the Izmir region that was shown to be a Shiga toxin
producing non-O157 serotype of STEC.
PMID- 27513250
TI - Impact of different anesthetic managements in outcomes of transcatheteraortic
valve implantation: the first Turkish experience.
AB - BACKGROUND/AIM: Transcatheter aortic valve implantation (TAVI) has emerged as a
new therapy in aortic stenosis patients with high operative risk. Advances in
experiences have shifted the choice of anesthesia from general to local
anesthesia and sedation for these patients. We compared our anesthetic
experiences in our institute in a period of 2.5 years. MATERIALS AND METHODS: A
total of 151 (86 females, 65 males, mean age 76 years) symptomatic aortic
stenosis patients undergoing transfemoral TAVI under general anesthesia (GA) (n =
79) and local anesthesia and sedation (LAS) (n = 72) were evaluated
retrospectively in regards to anesthetic issues. RESULTS: The mean European
System for Cardiac Operative Risk Evaluation (EuroSCORE) values of patients in
the GA and LAS groups were 17 and 12, respectively. The anesthesia duration was
significantly shorter in the LAS group (P < 0.001) and 16.7% of the patients in
the LAS group were switched to general anesthesia. Length of stay in the
intensive care unit was similar in the two groups. CONCLUSION: TAVI, applied in
high-risk populations, has many challenges for anesthesiologists. With
technological advances, it is possible to perform these procedures under sedation
with variable advantages. Thus, future studies in regard to anesthesia are
required for the success of the procedure and patient safety.
PMID- 27513251
TI - Increased IL-17 and TGF-beta serum levels in peripheral blood of patients with
beta-thalassemia major: implication for continual transfusions role in T helper17
mediated proinflammatory responses.
AB - BACKGROUND/AIM: Recent studies have shown that IL-17-producing CD4+ T helper
(Th17) cells play an important role in proinflammatory processes. In this report
we analyzed IL-17, IL-21, and TGF-beta serum levels in the peripheral blood of
Iranian beta-thalassemia major patients that clinically exhibited splenectomy and
iron overload. MATERIALS AND METHODS: Blood samples were collected from 43 beta
thalassemia patients and 43 healthy individuals with no history of malignancies
or autoimmune disorders. Then serum levels of IL-17, IL-21, and TGF-beta were
measured by enzyme linked immunosorbent assay (ELISA). RESULTS: The levels of IL
17 (P = 0.005) and TGF-beta (P < 0.001) were significantly higher in the
thalassemia patients compared to the healthy control. No significant differences
in the level of serum IL-21 was observed between the patients and controls. There
were no significant differences in serum levels of IL-17, IL-21, and TGF-beta
between patients with high or low serum levels of ferritin. CONCLUSION: Multiple
blood transfusions cause constant immune stimulation, as a result of repeated
exposure to new alloantigens. This might have significant effects on the
stimulation of cytokine producing cells in those patients and cytokine profile
can be used as a related marker for assessing disease severity and consequently
therapeutic intervention.
PMID- 27513252
TI - Sevoflurane versus propofol for electroconvulsive therapy: effects on seizure
parameters, anesthesia recovery, and the bispectral index.
AB - BACKGROUND/AIM: In this prospective randomized cross-over study we compare the
effects of sevoflurane versus propofol for electroconvulsive therapy (ECT)
anesthesia. MATERIALS AND METHODS: Twenty four patients (ASA I-III, 18-65 years
old) receiving ECT three times per week were included. Anesthesia was induced
with either propofol (0.75 mg/kg iv) or 5% sevoflurane in 100% oxygen.
Consecutive ECT sessions followed a 2 * 2 crossover design and a 2-day washout
period until the 10th ECT. Intravenous succinylcholine (1 mg/kg) was administered
while bispectral index (BIS) values were <=60%. RESULTS: Electromyogram and
electroencephalogram seizure duration, postictal suppression index, BIS values,
mean arterial blood pressure (MAP), heart rate, times to start of spontaneous
respiration, eye opening, understanding verbal commands, and side effects were
compared. No differences were found between the regimens for seizure activity and
recovery. At the end of ECT, MAP was higher with sevoflurane. Although BIS values
were higher after sevoflurane, no differences between the regimens were found in
terms of the need of muscle relaxants and in hypnosis levels. CONCLUSION:
Sevoflurane (5%) may be an effective alternative to propofol for induction of
anesthesia for ECT.
PMID- 27513253
TI - Intravitreal bevacizumab for retinopathy of prematurity in infants ineligible for
laser therapy.
AB - BACKGROUND/AIM: To evaluate refractive and strabismic results and the efficacy of
intravitreal bevacizumab in retinopathy of prematurity (ROP) ineligible for laser
therapy. MATERIALS AND METHODS: Thirty-nine eyes of 20 consecutive infants with
high-risk prethreshold ROP (11 infants with Zone I and 9 infants with Zone II
disease) who were ineligible for laser therapy due to systemic and/or ocular
conditions were treated with intravitreal bevacizumab. Recurrent retinopathy was
treated with laser ablation. The final follow-up examination was performed at
29.8 +/- 6.0 months of corrected age. RESULTS: All eyes responded to the initial
treatment with intravitreal bevacizumab. ROP recurred in 8 eyes (36%) with
initial Zone I disease and in only 2 eyes (11%) with initial Zone II disease,
which were successfully treated with laser ablation. No eye developed myopia
higher than 5.0 diopters. At 2.5 years, the Zone I eyes that had received laser
treatment appeared to be more myopic than the Zone I eyes treated only with
intravitreal bevacizumab (P = 0.038). A tendency for a higher incidence of
strabismus after additional laser therapy was also noted, but was not significant
(P = 0.22). CONCLUSION: Avoidance or even deferral of laser ablation with
intravitreal bevacizumab may lead to less myopization in ROP compared with
conventional laser treatment.
PMID- 27513254
TI - Epidemiology and cost of drug treatment of cancer in Northern Cyprus.
AB - BACKGROUND/AIM: To determine the epidemiology, the sociodemographic features, the
incidence and prevalence rate of cancer, and the cost of drug treatment in
Northern Cyprus. MATERIALS AND METHODS: All of the oncology prescriptions, cancer
pathology reports, and cancer referrals to overseas for 2011 were collected from
the state hospitals, the only private university hospital that provides oncology
services, and the Ministry of Health to prepare an epidemiological database. The
total cost of drug treatment at the state hospitals and cost of the most frequent
five cancer types were also calculated using the therapy protocols and the
expense of the drugs. RESULTS: The total incidence rate for all cancer cases in
2011 was 201 per 100,000 and the prevalence rate was 460 per 100,000. The five
most common cancer types were breast (19.8%), prostate (12.6%), colorectal
(9.7%), thyroid (6.4%), and lung (5.6%). The cost of drug treatment for cancer at
the state hospitals comprises 25% of the total medical budget of the Directorate
of Pharmaceuticals. Almost 1/3 of this amount was spent on drug treatment of
breast cancer. CONCLUSION: Breast cancer is the most frequent and the most costly
cancer type in Northern Cyprus. Of all the districts, the Guzelyurt-Lefke
District has the highest cancer rate.
PMID- 27513255
TI - Levels of nitric oxide, asymmetric dimethyl arginine, symmetric dimethyl
arginine,and L-arginine in patients with obsessive-compulsive disorder.
AB - BACKGROUND/AIM: We aimed to investigate and compare to healthy controls the
variations in the levels of nitric oxide (NO), asymmetric dimethyl arginine
(ADMA), symmetric dimethyl arginine (SDMA), and L-arginine levels in patients
with obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: We enrolled 30
patients with OCD and 30 healthy controls in the study consecutively. Diagnostic
interviews of all participants were conducted with the Structured Clinical
Interview for Axis I Disorders (SCID-I), and sociodemographic data of the
participants were recorded. Patients scoring 10 points or more on the Yale-Brown
Obsessive-Compulsive Scale were enrolled in the study. RESULTS: The NO levels of
patients with OCD were increased compared to the control group, but the increase
was not statistically significant (P > 0.05). However, patients with OCD had
significantly lower levels of ADMA, SDMA, and L-arginine compared with the
controls (P < 0.001). CONCLUSION: We found a significant decrease in ADMA, SDMA,
and L-arginine as NO inhibitors between the groups, possibly because of an
increase in NO. However, the insignificant increase in NO suggests that ADMA,
SDMA, and L-arginine play direct and potentially important roles in OCD biology.
PMID- 27513256
TI - NF-kappaBeta and SOD expression in preeclamptic placentas.
AB - BACKGROUND/AIM: Preeclampsia is a leading cause of maternal death in the
developing world. Our aim was to quantify and compare messenger (mRNA) expression
of nuclear factor-kappa beta (NF-kappaBeta) and superoxide dismutase (SOD) in
control patients with preeclampsia and without preeclampsia with or without
familial hereditary background. MATERIALS AND METHODS: Four groups of patients
were formed depending on the presence or absence of preeclampsia and presence or
absence of familial history for preeclampsia. NF-kappaBeta and SOD were measured
in human placentas by real-time quantitative polymerase chain reaction. The 2
DeltaDeltact analysis method was used to measure the difference in the relative
expression of the target genes in each group of patients. RESULTS: In NF
kappaBeta expression, there was an increase of 23.35% in the group of women with
preeclampsia versus women with preeclampsia without familial history. Regarding
SOD, there was a reduction of about 33.33% in the expression in women with
preeclampsia with familial history versus women with preeclampsia without
familial history. CONCLUSION: Familial presence of preeclampsia could predispose
to altered expression in SOD and NF-kappaBeta.
PMID- 27513257
TI - The effect of addition of ketamine to lidocaine on postoperative pain in
rhinoplasties.
AB - BACKGROUND/AIM: The objective of this study was to examine the effect of addition
of subanesthetic doses of ketamine to an epinephrine-lidocaine solution on
postoperative pain, analgesic use, and patient comfort during rhinoplasties.
MATERIALS AND METHODS: Ninety patients were randomly divided into three groups:
Group L, lidocaine with epinephrine; Group K, lidocaine with epinephrine plus
ketamine; and Group S (control group), physiological saline solution with
epinephrine. The local anesthetic solution was injected as preincisionally with
intranasal submucosal infiltration following induction of general anesthesia. We
evaluated visual pain score, analgesic demand, Wilson sedation score, and
antiemetic demand at 5, 15, and 30 min and 1, 2, 4, 6, 8, 16, and 24 h after the
operation. The patient satisfaction score was checked 24 h after the operation.
RESULTS: Visual pain score was significantly reduced in Group K in comparison
with the other groups and this group did not need any rescue analgesics (P <
0.05). The postoperative patient satisfaction scores were highest in Group K
compared with the other groups (P < 0.05). CONCLUSION: Addition of ketamine
solution to lidocaine for infiltration block during rhinoplasty was successful in
decreasing pain during postoperative periods and reducing analgesic consumption
during the first 24 h after the operation.
PMID- 27513258
TI - Complications of tracheobronchial foreign bodies.
AB - BACKGROUND/AIM: Tracheobronchial foreign bodies may cause several complications
in the respiratory system. We aimed to present the complications of
tracheobronchial foreign bodies. MATERIALS AND METHODS: Between January 1990 and
March 2015, 813 patients with suspected tracheobronchial foreign body aspiration
were hospitalized in our department. Patients with complications related to
foreign bodies in airways were included in this study. We retrospectively
evaluated the records of patients according to symptoms, foreign body type,
localizations, and complications. RESULTS: A foreign body was found in 701 of 813
patients (86.2%). Complications related to foreign bodies settled in airways were
seen in 96 patients (13.7%). The most common complications were atelectasis and
pneumonia in 36 (5.1%) and 26 (3.7%) patients, respectively. Other complications
were bronchiectasis (n = 12, 1.7%), cardiopulmonary arrest (n = 11, 1.6%),
bronchostenosis (n = 3, 0.4%), death (n = 2, 0.3%), migration of foreign body (n
= 2, 0.3%), pneumomediastinum (n = 2, 0.3%), tracheal perforation (n = 1, 0.15%),
pneumothorax (n = 1, 0.15%), and hemoptysis (n = 1, 0.15%). Coughing (n = 74,
77.1%) and diminished respiratory sounds (59.3%, n = 57) were the most common
findings. CONCLUSION: Careful evaluation and rapid intervention are life-saving
methods in tracheobronchial foreign body aspirations.
PMID- 27513259
TI - Long-term assessment of coronary care unit patient profile and outcomes: analyses
of the 12-years patient records.
AB - BACKGROUND/AIM: The aim of this study was to determine the patient profile,
treatment, and outcomes of a coronary care unit (CCU) by retrospective screening
of 12-year patient records. MATERIALS AND METHODS: The data of 13,463 patients
admitted to the CCU of a tertiary referral hospital between 1 January 1997 and 30
June 2008 were collected. The patients were assessed with respect to
demographics, admission diagnosis, treatment, and outcomes. RESULTS: The mean age
of patients was 61 +/- 13 years (66.7%, male). While the diagnosis of acute
coronary syndrome (ACS) accounted for 65%, the rate of ST elevation myocardial
infarction (STEMI) was 43.4%. Thrombolytic therapy was administered to 48.7% of
the patients with STEMI. Systolic heart failure was the most frequent disease
(11.9%) among the non-ACS diagnoses. The mortality rate of the CCU was 12.7% on
average; it increased gradually after 2005 when the CCU became a general
intensive care unit. CONCLUSION: This study is one of the largest comprehensive
analyses of patient profile and outcomes of a CCU. Despite advances in the
diagnosis and treatment of cardiac emergencies, the mortality rate of the CCU was
high. Serving as a general intensive care unit, the absence of a coronary
angiography laboratory and lower use of thrombolytic therapy for STEMI might be
responsible factors.
PMID- 27513260
TI - Evaluation of behavioral problems in patients with monosymptomaticnocturnal
enuresis: a prospective controlled trial.
AB - BACKGROUND/AIM: The aim of the present study was to evaluate the behavioral and
emotional patterns of patients with nocturnal enuresis (NE) and compare them with
those of healthy subjects. MATERIALS AND METHODS: Thirty-eight children and
adolescents with monosymptomatic NE who were admitted to our hospital's pediatric
and urologic outpatient clinics and 46 age-matched, healthy subjects were
enrolled in this study. To compare behavioral patterns in these patients, the
Child Behavior Checklist (CBCL) was used. Patients' ages, occupations,
educational, and socioeconomic status, and mothers' age at delivery were compared
in the two groups. One-way ANOVA was used for statistical analysis. RESULTS:
Enuretic children were found to have more behavioral problems than nonenuretic
children with regard to social (P = 0.008) and attention (P = 0.018) problems.
There were no significant differences in anxiety or attractiveness problems
between the groups (P > 0.05); however, patients with enuresis were more likely
to exhibit these behavioral problems than healthy subjects. The demographics of
the patients were significantly different in the two groups in favor of the
control group. CONCLUSION: It was shown that patients with enuresis have more
social and attention problems than the control group. Treating these patients
effectively will increase the likelihood that they will not develop behavioral
problems.
PMID- 27513261
TI - Potential drug-drug interactions in a medical intensive care unit of a university
hospital.
AB - BACKGROUND/AIM: Drug-drug interactions (DDIs) can impact patient safety.
Occurrence of clinically important DDIs is higher for intensive care unit (ICU)
patients. This observational study aimed to evaluate the potential DDIs in
medical ICU patients of a university hospital. MATERIALS AND METHODS: The Medical
Pharmacology Department organized consultation reports for ICU patients in order
to detect the DDIs. To focus on clinically important DDIs, interactions in the C,
D, or X risk rating categories of the Lexi-Interact online database were
analyzed. Frequency and clinical risk rating categories of DDIs were detected.
Relationship between number of prescriptions and DDIs were assessed. The most
frequent drug/drug groups were identified. RESULTS: Of 101 ICU patients, 45.5%
were found to have DDIs. We detected 125 C (72.2%), 37 D (21.4%), and 11 X (6.4%)
risk category interactions. A statistically significant increase in the number of
DDIs was shown with the number of prescriptions (P = 0.002). The most frequent
DDIs were between agents acting on the cardiovascular system and corticosteroids
(12.8%). CONCLUSION: Results of this study show that pharmacological consultation
plays a critical role in the recognition of DDIs for improvement of medication
management and effective therapeutic endpoints without any adverse or toxic
reactions.
PMID- 27513262
TI - Evaluation of the gastrointestinal findings of nodulocystic acnepatients during
systemic isotretinoin therapy.
AB - BACKGROUND/AIM: Systemic isotretinoin treatment is an effective treatment
modality for nodulocystic acne, the clinical use of which has been associated
with reports of adverse events. We conducted a prospective study with the aim of
determining the possible gastrointestinal and laboratory findings of nodulocystic
acne patients during systemic isotretinoin treatment. MATERIALS AND METHODS:
Seventy patients with nodulocystic acne completed the study. During the monthly
follow-up visits, liver function tests and lipid profiles of the patients were
evaluated and gastrointestinal system complaints were examined. RESULTS: We
recorded a significant elevation in liver function tests and lipid profiles of
the patients, the most prominent elevation being in plasma triglyceride
concentrations. We observed that nausea, dyspepsia, abdominal pain, and diarrhea
were the rare gastrointestinal symptoms encountered during systemic isotretinoin
therapy. Constipation and anorectal bleeding were relatively more common symptoms
and there seemed to be a relation between these two symptoms. CONCLUSION: Our
study is the first to analyze the gastrointestinal findings of patients during
systemic isotretinoin treatment. Dermatologists and gastroenterologists must keep
in mind that, as well as known laboratory findings like hypertriglyceridemia and
elevated liver function tests, systemic isotretinoin therapy may also cause
significant clinical gastrointestinal findings.
PMID- 27513263
TI - Prospects of curcumin as an additive in storage solutions: a study on
erythrocytes.
AB - BACKGROUND/AIM: Curcumin, a naturally occurring antioxidant, shows a wide variety
of medicinal properties. The possibility of utilizing curcumin as an additive in
storage solutions of blood has not been explored. The purpose of this study was
to analyze the effect of curcumin on erythrocytes during storage. MATERIALS AND
METHODS: Blood obtained from rats was stored (4 degrees C) for 20 days in
citrate-phosphate-dextrose-adenine-1 solution. Samples were divided into four
groups: 1) Controls; 2) Curcumin 10 mM; 3) Curcumin 30 mM; and 4) Curcumin 60 mM.
Every fifth day, hemoglobin, superoxide, antioxidant enzymes (superoxide
dismutase, catalase, and glutathione peroxidase (GSH-Px)), lipid peroxidation
(conjugate dienes and malondialdehyde (MDA)), protein oxidation (advanced
oxidation protein products (AOPP) and sulfhydryls (P-SH)), and hemolysis were
analyzed. RESULTS: Hemoglobin was successfully maintained, while superoxide
dismutase increased initially and decreased towards the end of storage.
Superoxide, catalase, GSH-Px, conjugate dienes, and AOPP were lower in the
curcumin groups than they were in the controls. MDA was higher in the curcumin
groups than in the controls. P-SH increased in the curcumin groups, while
hemolysis increased in all groups. CONCLUSION: Curcumin maintained hemoglobin and
modulated antioxidant enzymes throughout storage. However, curcumin could not
protect all proteins and lipids from oxidative damage completely. This study
opens up new avenues for using curcumin, in combination with other antioxidants,
as a component in storage solutions.
PMID- 27513264
TI - Evaluation of brain perfusion in Alzheimer disease with perfusion computed
tomography and comparison to elderly patient without dementia.
AB - BACKGROUND/AIM: The aim of this study was to evaluate perfusion computed
tomography (PCT) findings in patients with Alzheimer disease and to compare them
with those of patients without dementia. MATERIALS AND METHODS: PCT was performed
in 35 patients: 20 with Alzheimer disease (mean age, 69.7 +/- 5.5 years) and 15
control subjects (mean age, 67.5 +/- 3.5 years). Control subjects were elderly
individuals with no cognitive problems who were admitted with headaches. All PCT
examinations were performed on a 4-slice CT unit. The PCT analysis software
program was used to calculate regional cerebral blood flow (rCBF), regional
cerebral blood volume (rCBV), regional time-to-peak (rTTP) values in the
bilateral frontal, temporal, and occipital cortices, and bilateral lentiform
nucleus. RESULTS: rCBF values in the bilateral frontal and temporal cortices and
bilateral lentiform nucleus were significantly lower in the patients with
Alzheimer disease than in the control subjects. There were no significant
differences in rCBV values between Alzheimer disease and the control group. rTTP
values in all cortical areas and bilateral lentiform nucleus were significantly
higher in the patients with Alzheimer disease than in the control subjects.
CONCLUSION: PCT is a rapid and reliable imaging modality for evaluating brain
perfusion in Alzheimer disease.
PMID- 27513265
TI - The incidence of 18F-FDG PET/CT thyroid incidentalomas andthe prevalence of
malignancy: a prospective study.
AB - BACKGROUND/AIM: To determine the prevalence of malignancy in thyroid
incidentalomas (TIs) detected by fluorine-18 fluorodeoxyglucose (18F-FDG)
positron emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS:
18F-FDG PET/CT images were evaluated prospectively for the presence of thyroid
uptake. The patients with a TI were evaluated by an endocrinologist according to
the predefined diagnostic algorithm. The final diagnosis was obtained clinically
and/or by pathology. RESULTS: TI was detected in 4.2% of 4204 patients. A
malignant thyroid nodule was diagnosed in 29% and 33% of the focal and diffuse
focal uptake groups, respectively. However, no malignancy was detected in the
diffuse uptake group. The standardized maximum uptake values (SUVmax) of the
nodules were significantly higher in patients with thyroid malignancy than in
patients with benign nodules (P = 0.006). The calculated cut-off value of SUVmax
for malignancy was 3.5. In 2 patients in whom the cytopathological diagnosis was
benign, malignancy was diagnosed after total thyroidectomy. CONCLUSION: A
malignant nodule was present in one-third of the patients with focal or diffuse
focal uptake. A SUVmax value of 3.5 was considered as a cut-off value for the
differentiation of a malignant lesion. Benign cytology in fine-needle aspiration
biopsy for 2 patients underestimated a thyroid malignancy.
PMID- 27513266
TI - Three-dimensional cephalometric norms of Turkish Cypriots using CBCTimages
reconstructed from a volumetric rendering program in vivo.
AB - BACKGROUND/AIM: The aim of this study was to create a database of 3D
cephalometric measurements of Turkish Cypriot patients using a 3D rendering
software program. MATERIALS AND METHODS: The study population comprised 121
subjects who had undergone cone beam CT imaging (CBCT). Invivo 5.1 software was
used to generate cephalograms from the CBCT dataset that were then linked to the
3D hard-tissue surface representations. In total, 38 angular and 28 linear widely
used measurements were recorded. RESULTS: The results demonstrated that males had
significantly larger mean values than females for all linear measurements, except
for dentoalveolar parameters (P < 0.05). Additionally, significant differences
were found in most of the mandibular anteroposterior and vertical measurements,
especially SNB, GoGn/SN, FMA, and MP/SN, between the sexes (P < 0.05).
CONCLUSION: This is the first population-based study to focus solely on Turkish
Cypriots' craniofacial anatomy and orthodontic characteristics. The present
findings will produce 3D cephalometric normative data for the Cypriot population
and will be valuable for oral and maxillofacial surgeons and orthodontists in
Cyprus, the UK, Australia, Turkey, and other European countries who treat a large
number of Turkish Cypriot patients.
PMID- 27513267
TI - 1H-magnetic resonance spectroscopy in first episode and chronic schizophrenia
patients.
AB - BACKGROUND/AIM: The aim of this study was to compare metabolite levels of the
dorsolateral prefrontal cortex (DLPFC), anterior cingulate gyrus (ACG), thalamus,
and hippocampus in patients with chronic schizophrenia (CSPs) and first psychotic
episode patients (FEPs) by the use of magnetic resonance spectroscopy (MRS).
MATERIALS AND METHODS: Thirty CSPs, 20 FEPs, and 30 healthy subjects participated
in this study. N-Acetylaspartate (NAA), creatine, choline (Cho), and myoinositol
levels of the DLPFC, ACG, thalamus, and hippocampus were measured by 1H-MRS.
RESULTS: It was determined that the NAA/Cho ratio was lower in both the FEPs and
CSPs than the healthy controls in the DLPFC. DLPFC Cho levels were also higher in
CSPs than healthy controls. NAA levels in CSPs were significantly lower than in
the control group in the hippocampus. There was no significant difference in
neurometabolite levels and ratios in the ACG and thalamus between the groups.
CONCLUSION: This study supports neuronal dysfunction or loss of neuronal
integrity in the DLPFC and hippocampus in CSPs. FEPs showed less neuronal
dysfunction in the DLPFC, but not in the hippocampus. Our results suggest that
schizophrenic patients show brain metabolic changes with the onset of the
disorder in the DLPFC; these changes could be more apparent in the hippocampus as
the disease progresses to chronic stages.
PMID- 27513268
TI - PaCaHa inhibits proliferation of human cancer cells in vitro.
AB - BACKGROUND/AIM: The aim of this study was to investigate the antiproliferative
and cytotoxic effects of a newly synthesized molecule named paracetamol
acetohydroxamic acid (PaCaHa) on human neoplastic cell lines. MATERIALS AND
METHODS: A549, CRL 2923, HeLa, and ARPE were treated with various concentrations
of PaCaHa and DMSO (vehicle control). The cytotoxic/cytostatic effects of PaCaHa
were determined after a 24-h incubation period and compared to the DMSO control.
The cytotoxic and antiproliferative effects were determined by the trypan blue
dye exclusion and MTT methods. RESULTS: A higher susceptibility to PaCaHA was
found in CRL 2923 and HeLa cells, while A549 and ARPE cells were less responsive
to PaCaHa. The percent of cytotoxicity resulting from 400 ug/mL of PaCaHa were
>90 for CRL-2923 and HeLa, 68 for A549, and 64 for ARPE cells. The cytotoxic
difference between CRL-2923/HeLa and ARPE/A549 cells was significant (P < 0.05).
CONCLUSION: PaCaHa showed dose dependent cytotoxic and antiproliferative effects
on three distinct human cancer cell lines. The differential effect of PaCaHa on
different cancer cell lines suggests that PaCaHa could have a potential antitumor
effect on specific cancer types. These results support further comprehensive
studies on PaCaHa and its derivatives.
PMID- 27513269
TI - Determination of virulence and multidrug resistance genes with polymerase chain
reaction method in vancomycin-sensitive and -resistant enterococci isolated from
clinical samples.
AB - BACKGROUND/AIM: Enterococci play an important role in nosocomial infections.
Therefore, this study investigates multidrug resistance (MDR)1 gene areas in the
pathogenicity of enterococci and virulence genes in both vancomycin-sensitive
enterococci (VSE) and vancomycin-resistant enterococci (VRE) strains. MATERIALS
AND METHODS: Virulence genes and MDR genes of enterococci were investigated by
polymerase chain reaction (PCR). RESULTS: We evaluated a total of 116 isolates,
93 being VRE and 23 being VSE. In this study, 95.6% of VRE (n = 93) were
Enterococcus faecium (n = 89) and 4.3% were E. faecalis (n = 4), while 17.4% of
VSE (n = 23) were E. faecium (n = 4) and 82.6% were E. faecalis (n = 19). The
vanA MDR1 gene was detected in all VRE isolates. Among virulence genes, esp and
hyl were detected in E. faecium, an enterococcus with the highest resistance to
vancomycin, and gelE was detected in E. faecalis, an enterococcus with the
highest sensitivity to vancomycin. Three or more virulence genes were identified
only in VSE strains. We consider that it is a significant result that VSE had
more virulence genes than VRE. Only esp was seen in VRE E. faecium strains.
CONCLUSION: This study includes experimental results on the association of
virulence characteristics in VRE and VSE strains.
PMID- 27513270
TI - Investigating the in vitro synergistic activities of several antibiotic
combinationsagainst carbapenem-resistant Acinetobacter baumannii isolates.
AB - BACKGROUND/AIM: Acinetobacter baumannii (A. baumannii) is one of the most common
healthcare-associated infectious agents worldwide. The aim of this study was to
investigate the in vitro synergistic activities of several antibiotic
combinations against carbapenem-resistant (CR) A. baumannii isolates. MATERIALS
AND METHODS: Eighteen CR A. baumannii strains were isolated from the patients who
were hospitalized in the intensive care unit between June 2012 and August 2012.
The in vitro effects of single and binary combinations of meropenem (MEM),
colistin (CST), tigecycline (TGC), and sulbactam (SUL) on these isolates were
determined using the Epsilometer test (E-test) method. RESULTS: All 18 isolates
were resistant to MEM and SUL and susceptible to CST. TGC was detected as
susceptible in two of the isolates and intermediate susceptibility results were
observed in the remaining isolates. With MEM-CST and MEM-TGC combinations,
synergism was determined against all isolates. The synergistic and/or additive
effect ratios were detected in MEM-SUL, CST-SUL, TGC-SUL, and CST-TGC
combinations as 16.7%, 38.9%, 16.7%, and 5.6%, respectively. CONCLUSION: Among
the tested antimicrobial combinations, the in vitro combination of MEM with TGC
or CST was most effective against the CR A. baumannii strains.
PMID- 27513271
TI - Molecular prevalence and antibiotics resistance pattern of class A bla CTX-M-1
and bla TEM-1 beta lactamases in uropathogenic Escherichia coli isolates from
Pakistan.
AB - BACKGROUND/AIM: Extended spectrum beta lactamase (ESBL) production among E. coli
is one of the principal mechanisms that augment resistance to antibiotics. In the
current study the molecular detection of class A beta lactamases among
uropathogenic Escherichia coli was evaluated. MATERIALS AND METHODS: A total of
355 urine samples were collected from a tertiary care hospital in Peshawar. The
ESBL production among E. coli isolates was detected by using the disc synergy
diffusion method. Moreover, the molecular detection of bla TEM-1 and bla CTX-M-1
ESBLs, the antibiotic resistance pattern, and the minimum inhibitory
concentrations (MICs) were also documented. RESULTS: Among the 355 urine samples,
157 isolates were E. coli, and 23.56% of the isolates were ESBL E. coli. Among
phenotypic ESBL producers, bla CTX-M-1 and bla TEM-1 were found in 59.45% and
40.54% of the isolates, respectively. A high resistance rate was observed against
aztreonam (97.29%), while the lowest resistance was observed against imipenem
(2.7%). The MICs of ESBLs E. coli for ceftriaxone, ciprofloxacin, and gentamicin
was >512 ug/mL, 4 ug/mL to 128 ug/mL, and 1 ug/mL to 14 ug/mL respectively.
CONCLUSION: The present study showed that bla CTX-M-1 ESBL production is more
prevalent in our clinical E. coli isolates. More often the ESBLs were resistant
to commonly used antibiotics.
PMID- 27513272
TI - An investigation of the bactericidal activity of chlorhexidine digluconateagainst
multidrug-resistant hospital isolates.
AB - BACKGROUND/AIM: Hospital infections are among the most prominent medical problems
around the world. Using proper biocides in an appropriate way is critically
important in overcoming this problem. Several reports have suggested that
microorganisms may develop resistance or reduce their susceptibility to biocides,
similar to the case with antibiotics. In this study we aimed to determine the
antimicrobial activity of chlorhexidine digluconate against clinical isolates.
MATERIALS AND METHODS: The susceptibility of 120 hospital isolated strains of 7
bacterial genera against chlorhexidine digluconate was determined by agar
dilution test, using minimum inhibitory concentration (MIC) values and the EN
1040 Basic Bactericidal Activity Test to determine the bactericidal activity.
According to MIC values, Pseudomonas aeruginosa and Stenotrophomonas maltophilia
were found to be less susceptible to chlorhexidine digluconate. RESULTS:
Quantitative suspension test results showed that 4% chlorhexidine digluconate was
effective against antibiotic resistant and susceptible bacteria after 5 min of
contact time and can be safely used in our hospital. However, concentrations
below 4% chlorhexidine digluconate caused a decrease in bactericidal activity,
especially for Staphylococcus aureus and P. aeruginosa. CONCLUSION: It is crucial
to use biocides at appropriate concentrations and to perform surveillance studies
to trace resistance or low susceptibility patterns of S. aureus, P. aeruginosa,
and other hospital isolates.
PMID- 27513273
TI - Hepatoprotective and antidiabetic activities of Fraxinus angustifolia Vahl
extracts in animal models: characterization by high performance liquid
chromatography analysis.
AB - BACKGROUND/AIM: The present study was designed to explore antidiabetic and
hepatoprotective potentials of Fraxinus angustifolia leaf (FAL) and bark (FAB)
extracts in vivo. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic
rats, pretreated with the extracts (25 and 50 mg/kg), were monitored for fasting
blood glucose (FBG) levels. Hepatoprotective potential was examined after
injection of an excessive dose of paracetamol (10 g/60 kg) by analysis of
biochemical parameters (transaminases, bilirubin), malondialdehyde (MDA) levels,
and histological sections. high performance liquid chromatography analysis was
also performed for partial characterization. RESULTS: A considerable hypoglycemic
effect was noticed 2 h after the STZ-induction, with a higher efficiency (P <
0.05) for FAL (68%) as compared with FAB (57%). A significant (P < 0.05)
reduction in MDA was observed for paracetamol-fed mice pretreated with FAL (50
mg/kg), FAB (50 mg/kg), or both (25 mg/kg each) extracts, and the MDA levels for
the three conditions were 0.290 +/- 0.034, 0.340 +/- 0.038, and 0.25 +/- 0.058
nmoles/mg of liver tissue, respectively). Hence, simultaneous treatment provided
a better protection. Histological observations confirmed the higher
hepatoprotective potential of FAL over FAB extracts. CONCLUSION: The obtained
results indicate the possibility of pharmacological exploitation of F.
angustifolia extracts in the treatment of diabetes and associated liver diseases.
PMID- 27513274
TI - Intestinal trefoil factor increased the Bcl-2 level in a necrotizingenterocolitis
neonate rat model.
AB - BACKGROUND/AIM: The aim of this study was to investigate the therapeutic effect
of intestinal trefoil factor (ITF) on necrotizing enterocolitis (NEC) by
observing the pathological changes and detecting the protein level differences in
Caspase-3, Bax, and Bcl-2 in an NEC neonate rat model. MATERIALS AND METHODS: A
Wistar rat model of NEC was established and 30 one-day-old neonate Wistar rats
were randomly divided into three groups including a normal control (group A), NEC
rats treated with 0.2 ml physiological saline through intraperitoneal (i.p.)
injection (group B), and NEC rats treated with 0.2 mg ITF by i.p injection (group
C). RESULTS: Compared with group B, there were statistically significant
differences in Caspase-3, Bax, and Bcl-2 levels in groups A and C(P < 0.05).
Moreover, there was a significant difference in the Bcl-2 level between groups A
and B (P < 0.05). CONCLUSION: ITF alleviated injury of the intestinal tract in
neonate rats with NEC and this mechanism was possibly related to a reduction in
the expression of Caspase-3 and Bax and the increase in Bcl-2 expression.
PMID- 27513275
TI - The effects of bupivacaine combined with different adjuvants on block onset and
duration and on ion channel expressions (SCN9A, TRPM) in sciatic nerve block in
rats.
AB - BACKGROUND/AIM: The objective of this experimental study was to examine the
effects of epinephrine, dexmedetomidine, and clonidine added as adjuvants to
bupivacaine on block onset and effect times, as well as the effects on the Na+
and Ca+2 channel gene expressions, which may indicate cell damage in the sciatic
nerve cell membrane. MATERIALS AND METHODS: Rats were divided into five groups:
Group S (sham), saline solution; Group B, bupivacaine; Group BD, bupivacaine +
dexmedetomidine; Group BC, bupivacaine + clonidine; and Group BE, bupivacaine +
epinephrine. For each group, 0.2 mL of local anesthetic was injected into the
sciatic nerve bifurcation point of the right leg. Sensory (proprioceptive and
nociceptive block) and motor block onset and ending times were recorded. RESULTS:
The shortest onset time for the examined sciatic block was observed in the BC
group, whereas the longest sensory and motor block times were observed in the BD
group. The present data suggest suppressed TRPM7 and increased TRPM2 in the
groups other than the BE group. CONCLUSION: Clonidine is more suitable for fast
onset of peripheral nerve blocks, whereas the addition of dexmedetomidine is
better in terms of duration. Because the SCN9A and TRPM2,4,7 expression ratios of
the BE group showed the least amount of change, this group had the best cellular
integrity.
PMID- 27513276
TI - Paternal exposure to low-dose lead acetate: effect on implantation rate,pregnancy
outcome, and sex ratio in mice.
AB - BACKGROUND/AIM: It has been reported from in vivo exposed experimental animals
that paternal lead exposure reduces birth rate; however, there is limited
evidence to suggest a decrease in the proportion of male births. This study
investigated the role of paternal exposure to lower lead acetate doses on early
embryonic development (implantation) and the sex ratio of their offspring.
MATERIALS AND METHODS: In total 180 Swiss Webster mice were used (60 male and 120
female). The males were divided into 3 groups: G1 (untreated group), G2 (treated
daily with 50 ug/kg BW lead acetate), and G3 (treated daily with 100 ug/kg BW
lead acetate). The implantation success rate, pregnancy outcome, and sex ratio
were measured. RESULTS: The results showed a highly significant reduction in both
the percentage of implantation rate and the number of offspring in the G3 mice,
but there was no signification difference for the G2 mice. There was a slight
insignificant reduction in the number of newborn males compared with females for
both G2 and G3 mice. CONCLUSION: The findings of this study suggest lead exposure
in experimental animals reduces implantation rate with paternal BLL of 28 ug/dL
and the sex ratio for offspring showed a slight insignificant reduction with both
paternal BLLs of 23.5 ug/dL and 28 ug/dL.
PMID- 27513277
TI - First report on the distribution of 3435C>T ABCB1/MDR1polymorphism in healthy
Bosniak population.
PMID- 27513279
TI - Why Your ZIP Code Matters More Than Your Genetic Code: Promoting Healthy Outcomes
from Mother to Child.
AB - Health equity has long been the dominant theme in the work of the Aetna
Foundation. Recent data have focused on disparities through another lens,
particularly the correlation between where people live (i.e., ZIP code) and their
quality-and length-of life. In various cities across America, average life
expectancies in certain communities are 20-30 years shorter than those mere miles
away. In general, health disparities are founded on a complex interplay of
racial, economic, educational, and other social factors. For example,
breastfeeding rates in the United States differ significantly depending upon the
race and income of the mother. Government policy makers are acutely aware of
these disparities, but recent health system reforms have focused predominately on
the processes used to administer, finance, and deliver care. What is needed is an
approach that considers the health and wellness of all people in a geographic
area, beyond established patients, and that measures more than clinical factors
such as genetics, environmental health, social circumstances, and individual
behaviors. Solutions also must extend beyond the traditional healthcare arena. In
particular, novel technological innovations show promise to bridge gaps between
our healthcare capabilities and the needs of underserved populations. Digital
tools are poised to revolutionize measurement, diagnostics, treatment, and global
aspect of our healthcare system. The Aetna Foundation views technology as a core
strategy in reducing health inequities through an approach that addresses both
clinical and social factors in populations to dismantle the persistent paradigm
of ZIP code as personal health destiny.
PMID- 27513278
TI - Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with
Lymphangioleiomyomatosis.
AB - RATIONALE: Sirolimus has been shown in a randomized, controlled clinical trial to
stabilize lung function in patients with lymphangioleiomyomatosis (LAM) treated
for a 12-month time period; however the pretreatment decline in lung function
after the drug was discontinued indicated that continued exposure is required to
suppress disease progression. OBJECTIVES: To elucidate the durability and
tolerability of long-term sirolimus treatment in Asian patients with LAM.
METHODS: We conducted a single-arm, open-label, investigator-initiated safety and
efficacy study of sirolimus in 63 women with LAM at 9 sites in Japan. Subjects
received sirolimus for 2 years at doses adjusted to maintain a trough blood level
of 5-15 ng/ml. MEASUREMENTS AND MAIN RESULTS: Fifty-two subjects (82.5%)
completed the trial with mean drug compliance of more than 80% overall during the
study. The number of adverse events was greatest during the initial 6 months of
therapy, but they continued to occur with declining frequency throughout the 2
year study period. Of the 1,549 adverse events, 27 were classified as serious,
including reversible sirolimus pneumonitis in 3 patients. New
hypercholesterolemia occurred in 30 patients (48%); microcytosis in 10 patients;
loss of body weight in 33 patients; and increase in blood pressure that required
treatment in 5 patients. FEV1, FVC, and quality-of-life parameters were stable in
the overall study cohort during the study period, but baseline to 2-year
improvements in lung function occurred in the subset of patients with a prior
history of chylothorax. CONCLUSIONS: Although long-term sirolimus treatment of
Asian patients with LAM was associated with a large number of adverse events,
including three episodes of pneumonitis, most patients completed the 2-year
course of medication with good drug compliance and stable quality of life and
lung function.
PMID- 27513281
TI - Synergetic Solvent Engineering of Film Nanomorphology to Enhance Planar Perylene
Diimide-Based Organic Photovoltaics.
AB - Solvent additive has proven as a useful protocol for improving the film
nanomorphology of polymer donor (D): fullerene acceptor (A) blends in bulk
heterojunction (BHJ) photovoltaic cells. By contrast, the effect of such solvent
additive on nonfullerene BHJ cells based on perylene diimide acceptor, for
instance, is less effective because of their highly planar structure and strong
pi-aggregation in solid state. Here we choose N,N'-bis(1-ethylpropyl)-perylene
3,4,9,10-tetracarboxylic diimide (PDI) and thieno[3,4-b]thiophene-alt
benzodithiophene (PTB7) as a model D:A blend system to investigate how solvent
engineering strategy synergistically impacts the blend film nanomorphology. Based
on the differences of solvent volatility and solubility, various host solvents
chloroform (CF) and chlorobenzene (CB) and solvent additives-chloronaphthalene
(CN) and 1,8-diiodooctane (DIO) are selected for comparative studies. It is found
that the pi-aggregation of PDIs can be largely suppressed by using low-boiling
point (Tb) CF solvent, yet enlarged by using high-Tb CB. Moreover, CN additive
provides good solubility of PDI molecules and hence reduces large PDI aggregates
in CB system, while DIO exhibiting poor solubility works oppositely. By contrast,
DIO that presents larger Tb difference with CF prolongs the film-forming, which
assists in optimizing the PDI aggregation and increases the intermixed PTB7:PDI
phases more significantly than CN in CF system, yielding the finest phase
separation morphology and balanced charge mobility. Consequently, the inverted
BHJ cells based on CF-processed PTB7:PDI blend film with 0.4 vol % DIO exhibit
the highest PCE of 3.55% with a fill factor of 56%, both of which are among the
best performance for such a paradigm PTB7:PDI blend-based BHJ cells.
PMID- 27513280
TI - Simultaneously elevated exhaled nitric oxide and serum-eosinophil cationic
protein relate to recent asthma events in asthmatics in a cross-sectional
population-based study.
AB - BACKGROUND: We have reported that increased fraction of exhaled nitric oxide
(FeNO), a measure of TH2 -driven airway inflammation, and blood eosinophil count,
a marker of systemic eosinophil inflammation, correlated with asthma attacks in a
population-based study. OBJECTIVE: To investigate the relation between
simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels
and asthma events among asthmatics. METHODS: Measurements of FeNO (elevated >= 25
ppb) and S-ECP (elevated >= 20 ng/mL) were performed in 339 adult asthmatics.
Asthma events (attacks and symptoms) were self-reported. RESULTS: Simultaneously
normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with
simultaneously elevated S-ECP and FeNO (13% of the population) had a higher
prevalence of asthma attacks in the preceding 3 months than subjects with normal
S-ECP and FeNO (51% vs. 25%, P = 0.001). This was not found for subjects with
singly elevated S-ECP (P = 0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and
FeNO levels were independently associated with asthma attacks in the preceding 3
months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8).
CONCLUSIONS: Simultaneously elevated FeNO and S-ECP levels were related to a
higher likelihood of asthma attacks in the preceding 3 months. This indicates
that there is a value in measuring both FeNO and systemic eosinophilic
inflammation in patients with asthma to identify individuals at high risk of
exacerbations. CLINICAL RELEVANCE: FeNO and S-ECP are markers for inflammation in
asthma, but are dependent on different inflammatory pathways and weakly
correlated. Simultaneous measurements of both offer better risk characterization
of adult asthmatics.
PMID- 27513282
TI - Novel porous poly(propylene fumarate-co-caprolactone) scaffolds fabricated by
thermally induced phase separation.
AB - Scaffolds with porous structures are highly applicable for tissue engineering and
regenerative medicine. In the present study, 3-dimensional poly(propylene
fumarate-co-caprolactone) [P(PF-co-CL)] scaffolds were fabricated from a P(PF-co
CL)-dioxane-water ternary system through thermally induced phase separation
(TIPS). Cloud points of P(PF-co-CL) in dioxane-water solutions increased with
increased solute concentration, but increased dioxane composition decreased cloud
point. Among 3 polymer concentrations (4, 8, and 12 wt%), 8 wt% P(PF-co-CL)
scaffolds exhibited the best pore interconnectivity, with large, regular sized
pores. Scaffolds were formed in 3 solutions with different dioxane-water ratios
(74/26, 78/22, and 82/18 wt/wt); the 78/22 wt/wt scaffold had finger-shaped
patterns with better interconnectivity than scaffolds from the other two ratios.
Higher dioxane-water ratios resulted in a larger contact angle and thus less
wettability for the fabricated scaffold, while scaffolds fabricated from higher
concentrations of P(PF-co-CL) or high dioxane-water ratios had better
biomineralization after soaking in simulated body fluid. In vitro cell viability
testing showed the scaffolds had good biocompatibility with both bone and nerve
cells. The results indicate that the polymer concentration and solvents ratio
significantly affect the formation of porous structures, and optimum processing
parameters were found to be 8% polymer concentration and 22% to 24% water
content. These porous P(PF-co-CL) scaffolds fabricated via TIPS may be useful in
various tissue engineering applications (c) 2016 Wiley Periodicals, Inc. J Biomed
Mater Res Part A: 105A: 226-235, 2017.
PMID- 27513283
TI - Maternal anxiety and physiological reactivity as mechanisms to explain
overprotective primiparous parenting behaviors.
AB - In this study, we sought to determine whether the affective and physiological
experience of primiparous, or first-time, motherhood is distinct from multiparous
motherhood, how the child's level of inhibited temperament impacts it, and if
such a temperament results in overprotective parenting behaviors. A total of 117
mothers and their 24-month-old toddlers participated in novelty tasks designed to
elicit parenting behaviors and toddler's typical fear reactions. Mothers also
completed a battery of questionnaires. Results suggest that primiparous mothers
experienced more worry, which was associated with increased overprotective
parenting behaviors. Primiparous mothers also demonstrated greater physiological
(i.e., cortisol) reactivity while watching their first-born children interact
with novel stimuli, but how this related to overprotective parenting was
dependent on the child's level of inhibition. Specifically, primiparous mothers
displayed more cortisol reactivity with their uninhibited toddlers, which
indirectly linked parity to less overprotective parenting behaviors. Primiparous
mothers of highly inhibited toddlers displayed greater overprotective parenting
behaviors, independent of maternal cortisol reactivity. The results indicate that
the transition to motherhood is a unique experience associated with greater worry
and physiological reactivity and is meaningfully influenced by the toddler's
temperament. Distinctions in both observed and self-reported overprotective
parenting are evident through considering the dynamic interaction of these
various aspects. (PsycINFO Database Record
PMID- 27513284
TI - Happy Family Kitchen: A community-based research for enhancing family
communication and well-being in Hong Kong.
AB - Urban families worldwide are often characterized by busy working lives which
leave little time for family gatherings and communication. The Happy Family
Kitchen project, which emphasized cooking and dining with family members, was
conducted in a deprived district in Hong Kong. We hypothesized that the community
based family intervention, derived from a positive psychology framework, can
improve family communication, family well-being, and subjective happiness. Twenty
three social service units organized and delivered the intervention programs for
1,419 individuals from 612 families. The core intervention was developed with
emphasis on 1 of 5 positive psychology themes: gratitude, flow, happiness,
health, and savoring. Intervention outcomes were assessed at preintervention,
immediate postintervention, and 6 weeks and 12 weeks postintervention. Results
showed that family communication, family well-being, and subjective happiness
improved with small effect sizes which were sustained up to 12 weeks. The
gratitude intervention improved all of the outcome measures. Qualitative data
provided additional evidence for effectiveness with in-depth insights into family
dynamics. We concluded that this brief intervention was a low-cost and simple
approach to improve family communication and well-being. (PsycINFO Database
Record
PMID- 27513285
TI - Low-income, nonresident fathers' coparenting with multiple mothers and relatives:
Effects on fathering.
AB - Low-income, nonresident fathers are often involved in complex coparenting
networks that may involve multiple mothers, relatives, and other adults. However,
the coparenting literature has often obscured this complexity through limiting
attention to father-mother relationships. The current study used family systems
theory to examine the effects of fathers' coparenting with mothers and relatives
on fathers' parenting self-efficacy, father-child closeness, and father-child
conflict. Predictors included the number of fathers' coparenting mothers and
relatives, the quality of those coparenting relationships, and coparenting
alliances specifically between fathers and the biological mother of a target
child. Approximately 19% of a community sample of fathers (N = 401) reported more
than 1 mother in their coparenting network, and 63% reported at least 1 relative.
Overall, fathers who reported having more-cooperative coparenting relatives in
their networks reported higher parenting self-efficacy and father-child
closeness. We further noted a race or ethnicity interaction effect for closeness
and conflict, such that having more-cooperative coparenting relatives was
associated with increased closeness for non-Hispanic Black fathers but not for
non-Hispanic White fathers. Amount of cooperation with coparenting relatives was
associated with increased conflict for non-Hispanic Black fathers but not for
Hispanic fathers. Implications for future research and practice are discussed.
(PsycINFO Database Record
PMID- 27513286
TI - Adolescent functioning in housing and family contexts: A mixed methods study.
AB - Although adolescents begin to seek autonomy and strive to be out of the home on
their own, the housing context remains the primary setting of their daily lives.
Using survey and ethnographic data from Welfare, Children, and Families: A Three
City Study (e.g., Winston et al., 1999), this study explored quantitatively and
qualitatively how two salient aspects of the housing context, physical housing
problems and household size, were associated with low-income adolescents'
emotional and academic functioning, and how these associations were modified by
mother-adolescent relationships (specifically, trust and communication) and
gender. Results of cross-lagged hierarchical linear models suggest that
adolescents living in homes with more housing problems had more mental health
symptoms, whereas living in larger households was associated with higher
achievement, but only in the context of lower quality mother-adolescent
relationships. Qualitative analyses helped to interpret these results by
illuminating potential pathways underlying associations observed in quantitative
results.
PMID- 27513287
TI - "It takes two to take": Caregiving style, relational entitlement, and medication
adherence.
AB - Partners' support has been associated with both patients' increased and decreased
inclination toward health-promoting behaviors. Our hypothesis for understanding
this enigma is that it is the interplay between partners' manner of care
provision and patients' ability to accept these care efforts that may best
predict patients' adherence. Thus, the current study's main goal was to examine
the contribution of the interaction between caregivers' support style (sensitive
and compulsive) and cardiac patients' sense of relational entitlement
(restricted, excessive, assertive, entitlement expectations) to patients'
medication adherence. The Adult Caregiving Questionnaire, the Sense of Relational
Entitlement Scale, and the Medication Adherence Report Scale were administered to
114 cardiac patients and their partners, during patients' hospitalizations and 6
months later. The lowest levels of medication adherence were detected among
patients high on restricted entitlement who were married to partners high on
compulsive caregiving style. These findings strengthen our claim that it is the
interaction between recipients' personality and providers' support style which
explain self-regulatory processes that arise during times of family medical
crises. (PsycINFO Database Record
PMID- 27513288
TI - Elucidating the pH-Dependent Structural Transition of T7 Bacteriophage Endolysin.
AB - Bacteriophages are the most abundant and diverse biological entities on earth.
Bacteriophage endolysins are unique peptidoglycan hydrolases and have huge
potential as effective enzybiotics in various infectious models. T7 bacteriophage
endolysin (T7L), also known as N-acetylmuramoyl-l-alanine amidase or T7 lysozyme,
is a 17 kDa protein that lyses a range of Gram-negative bacteria by hydrolyzing
the amide bond between N-acetylmuramoyl residues and the l-alanine of the
peptidoglycan layer. Although the activity profiles of several of the T7 family
members have been known for many years, the molecular basis for their pH
dependent differential activity is not clear. In this study, we explored the pH
induced structural, stability, and activity characteristics of T7L by applying a
variety of biophysical techniques and protein nuclear magnetic resonance (NMR)
spectroscopy. Our studies established a reversible structural transition of T7L
below pH 6 and the formation of a partially denatured conformation at pH 3. This
low-pH conformation is thermally stable and exposed its hydrophobic pockets.
Further, NMR relaxation measurements and structural analysis unraveled that T7L
is highly dynamic in its native state and a network of His residues are
responsible for the observed pH-dependent conformational dynamics and
transitions. As bacteriophage chimeric and engineered endolysins are being
developed as novel therapeutics against multiple drug resistance pathogens, we
believe that our results are of great help in designing these entities as
broadband antimicrobial and/or antibacterial agents.
PMID- 27513289
TI - The Effect of Delivery System and Light Activation on Tooth Whitening Efficacy
and Hydrogen Peroxide Penetration.
AB - PURPOSE: To evaluate the whitening efficacy of a new two-layer technology in
office system compared to a conventional gel-type system and determine hydrogen
peroxide penetration (HPP) into the pulp cavity. MATERIALS AND METHODS: Extracted
molars (n = 60) were assigned to group NC: glycerol gel; group QPRO: 20% HP
varnish (Zoom Quick Pro, Philips Oral Healthcare); group ZOOM_NL: 25% HP gel
(Zoom Chairside Whitening); and group ZOOM_WL: 25% HP gel (Zoom Chairside
Whitening) with light-activation. HPP levels were estimated with leucocrystal
violet and horseradish-peroxidase. Instrumental color measurements were performed
at baseline (T0 ), 1-day post first whitening (T1 ), 1-day post second whitening
(T2 ), 1-day post third whitening (T3 ), and 1-month post whitening (T4 ). One
way analysis of variance followed by post hoc Tukey's HSD test was performed to
detect difference in DeltaE* and HP penetration levels (alpha = 0.05). RESULTS:
DeltaE* of NC was lower than other groups, whereas DeltaE* of ZOOM_WL was greater
than the other three groups, at T3 and T4 . Mean HPP level obtained from ZOOM_WL
(1.568 +/- 0.753 MUg/mL) was significantly greater than those obtained from the
other groups, whereas the mean HPP level observed in NC group (-0.131 +/- 0.003
MUg/mL) was significantly lower than the other groups. CONCLUSIONS: Tooth
whitening efficacy and HPP levels vary based on whitening systems used. CLINICAL
SIGNIFICANCE: The two-layer technology in-office varnish system may be an
alternative whitening option to reduce chair time in the office. (J Esthet Restor
Dent 28:313-320, 2016).
PMID- 27513290
TI - A Study of Boratriazaroles: An Underdeveloped Class of Heterocycles.
AB - Boratriazaroles were discovered in the late 1960s, and since then, a variety of
substituted boratriazarole derivatives have been prepared. However, no study has
compared the properties of these BN heterocycles with their carbon-based
analogues. In this work, we have prepared a series of boratriazarole derivatives
and have investigated how structural variations in the five-member heterocycle
affect photophysical and electronic properties. Boratriazaroles exhibit
absorption and emission spectra comparable to those of their azacycle analogues
but have a markedly lower quantum yield. The quantum yield can be increased with
the incorporation of a 2-pyridyl substitution on the boratriazaroles, and the
structural and optoelectronic properties are further influenced by the nature of
the B-aryl substituent. Introducing an electron-deficient p-cyano group on the B
phenyl substituent creates a twisted intramolecular charge transfer state that
causes a large Stokes shift and positive solvatochromism. Our work should serve
to guide future synthetic efforts toward the application of boratriazaroles in
materials science.
PMID- 27513293
TI - MicroRNA Let-7b inhibits keratinocyte migration in cutaneous wound healing by
targeting IGF2BP2.
AB - Wound healing is a complex process which involves proliferation and migration of
keratinocyte for closure of epidermal injuries. A member of microRNA family, let
7b, has been expressed in mammalian skin, but its exact role in keratinocyte
migration is still not in knowledge. Here, we showed that let-7b regulates
keratinocyte migration by targeting the insulin-like growth factor IGF2BP2.
Overexpression of let-7b led to reduced HaCaT cell migration, while knockdown of
let-7b resulted in enhanced migration. Furthermore, let-7b was decreased during
wound healing in wild-type mice, which led us to construct the transgenic mice
with overexpression of let-7b in skin. The re-epithelialization of epidermis of
let-7b transgenic mice was reduced during wound healing. Using bioinformatics
prediction software and a reporter gene assay, we found that IGF2BP2 was a target
of let-7b, which contributes to keratinocyte migration. Introduction of an
expression vector of IGF2BP2 also rescued let-7b-induced migration deficiency,
which confirms that IGF2BP2 is an important target for let-7b regulation. Our
findings suggest that let-7b significantly delayed the re-epithelialization
possibly due to reduction of keratinocyte migration and restraints IGF2BP2 during
skin wound healing.
PMID- 27513294
TI - Descending projections from the inferior colliculus to the dorsal cochlear
nucleus are excitatory.
AB - Ascending projections of the dorsal cochlear nucleus (DCN) target primarily the
contralateral inferior colliculus (IC). In turn, the IC sends bilateral
descending projections back to the DCN. We sought to determine the nature of
these descending axons in order to infer circuit mechanisms of signal processing
at one of the earliest stages of the central auditory pathway. An anterograde
tracer was injected in the IC of CBA/Ca mice to reveal terminal characteristics
of the descending axons. Retrograde tracer deposits were made in the DCN of
CBA/Ca and transgenic GAD67-EGFP mice to investigate the cells giving rise to
these projections. A multiunit best frequency was determined for each injection
site. Brains were processed by using standard histologic methods for
visualization and examined by fluorescent, brightfield, and electron microscopy.
Descending projections from the IC were inferred to be excitatory because the
cell bodies of retrogradely labeled neurons did not colabel with EGFP expression
in neurons of GAD67-EGFP mice. Furthermore, additional experiments yielded no
glycinergic or cholinergic positive cells in the IC, and descending projections
to the DCN were colabeled with antibodies against VGluT2, a glutamate
transporter. Anterogradely labeled endings in the DCN formed asymmetric
postsynaptic densities, a feature of excitatory neurotransmission. These
descending projections to the DCN from the IC were topographic and suggest a
feedback pathway that could underlie a frequency-specific enhancement of some
acoustic signals and suppression of others. The involvement of this IC-DCN
circuit is especially noteworthy when considering the gating of ascending signal
streams for auditory processing. J. Comp. Neurol. 525:773-793, 2017. (c) 2016
Wiley Periodicals, Inc.
PMID- 27513295
TI - A Catalyst-Controlled Aerobic Coupling of ortho-Quinones and Phenols Applied to
the Synthesis of Aryl Ethers.
AB - ortho-Quinones are underutilized six-carbon-atom building blocks. We herein
describe an approach for controlling their reactivity with copper that gives rise
to a catalytic aerobic cross-coupling with phenols. The resulting aryl ethers are
generated in high yield across a broad substrate scope under mild conditions.
This method represents a unique example where the covalent modification of an
ortho-quinone is catalyzed by a transition metal, creating new opportunities for
their utilization in synthesis.
PMID- 27513296
TI - Cost-effectiveness of supervised exercise therapy compared with endovascular
revascularization for intermittent claudication.
AB - BACKGROUND: Current guidelines recommend supervised exercise therapy (SET) as the
preferred initial treatment for patients with intermittent claudication. The
availability of SET programmes is, however, limited and such programmes are often
not reimbursed. Evidence for the long-term cost-effectiveness of SET compared
with endovascular revascularization (ER) as primary treatment for intermittent
claudication might aid widespread adoption in clinical practice. METHODS: A
Markov model was constructed to determine the incremental costs, incremental
quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio of
SET versus ER for a hypothetical cohort of patients with newly diagnosed
intermittent claudication, from the Dutch healthcare payer's perspective. In the
event of primary treatment failure, possible secondary interventions were repeat
ER, open revascularization or major amputation. Data sources for model parameters
included original data from two RCTs, as well as evidence from the medical
literature. The robustness of the results was tested with probabilistic and one
way sensitivity analysis. RESULTS: Considering a 5-year time horizon,
probabilistic sensitivity analysis revealed that SET was associated with cost
savings compared with ER (-?6412, 95 per cent credibility interval (CrI) -?11 874
to -?1939). The mean difference in effectiveness was -0.07 (95 per cent CrI -0.27
to 0.16) QALYs. ER was associated with an additional ?91 600 per QALY gained
compared with SET. One-way sensitivity analysis indicated more favourable cost
effectiveness for ER in subsets of patients with low quality-of-life scores at
baseline. CONCLUSION: SET is a more cost-effective primary treatment for
intermittent claudication than ER. These results support implementation of
supervised exercise programmes in clinical practice.
PMID- 27513298
TI - Consuming energy drinks at the age of 14 predicted legal and illegal substance
use at 16.
AB - AIM: This study examined whether consuming energy drinks at the age of 14
predicted substance use at 16. METHODS: We followed 621 youths from an area of
Switzerland who completed a longitudinal online survey in both 2012 and 2014 when
they were 14 and 16 years of age. At 14, participants, who were divided into
nonenergy drink users (n = 262), occasional users (n = 183) and regular users (n
= 176), reported demographic, health-related and substance use data. Substance
use at 16 was assessed through logistic regression using nonusers as the
reference group and controlling for significant variables at 14. RESULTS: At the
bivariate level, energy drink consumption was associated with substance use at
both 14 and 16. Energy drink consumers were also more likely to be male, older,
less academic, sleep less on schooldays and live in an urban area. In the
multivariate analysis, smokers, alcohol misusers and cannabis users at the age of
16 were significantly more likely to have been regular energy drink users at the
age of 14. CONCLUSION: Consuming energy drinks at 14 years of age predicted using
legal and illegal substances at 16. Health providers should screen young
adolescents for energy drink use and closely monitor weekly users.
PMID- 27513299
TI - Photoswitchable NIR-Emitting Gold Nanoparticles.
AB - Photo-switching of the NIR emission of gold nanoparticles (GNP) upon photo
isomerization of azobenzene ligands, bound to the surface, is demonstrated.
Photophysical results confirm the occurrence of an excitation energy transfer
process from the ligands to the GNP that produces sensitized NIR emission.
Because of this process, the excitation efficiency of the gold core, upon
excitation of the ligands, is much higher for the trans form than for the cis
one, and t->c photo-isomerization causes a relevant decrease of the GNP NIR
emission. As a consequence, photo-isomerization can be monitored by ratiometric
detection of the NIR emission upon dual excitation. The photo-isomerization
process was followed in real-time through the simultaneous detection of
absorbance and luminescence changes using a dedicated setup. Surprisingly, the
photo-isomerization rate of the ligands, bound to the GNP surface, was the same
as measured for the chromophores in solution. This outcome demonstrated that
excitation energy transfer to gold assists photo-isomerization, rather than
competing with it. These results pave the road to the development of new, NIR
emitting, stimuli-responsive nanomaterials for theranostics.
PMID- 27513300
TI - The Rho-ROCK pathway as a new pathological mechanism of innate immune subversion
in chronic myeloid leukaemia.
AB - CD1d-restricted invariant natural killer T (iNKT) cells are believed to play a
key role in cancer immune surveillance, and are functionally deficient in
patients with chronic myeloid leukaemia (CML). Herein, we have hypothesized that
this defect might originate from BCR-ABL-dependent dysfunctions in myeloid
dendritic cells (mDCs). Indeed, flow cytometry and confocal microscopy revealed
that cell surface expression of CD1d was downregulated in CML mDCs, relative to
healthy donor (HD) controls. The decreased cell surface display of CD1d could not
be ascribed to defective mDC differentiation, as attested by normal expression of
HLA-DR and the CD86 maturation marker. On the other hand, reduced membrane
expression was not associated with decreased intracytoplasmic levels of CD1d or
its mRNA transcripts, consistent with intracellular retention. In vitro treatment
of CML mDCs with the Rho-associated protein kinase (ROCK) inhibitor Y-27632
partially restored both cell surface CD1d expression and CD1d-mediated antigen
presentation, whereas it had no effect on HD mDCs. An inhibitor of BCR-ABL
tyrosine kinase (TK), imatinib mesylate (IM), had no such activity. Similar
recovery of CD1d expression occurred with fasudil, another ROCK inhibitor that is
commonly used in clinical trials. Our data support the conclusion that BCR-ABL
dependent ROCK, but not TK, is involved in CD1d downregulation. We propose that
ROCK, which is most likely activated by the DH/PH domain of BCR-ABL, mediates
iNKT-cell immune subversion in CML patients by downregulating CD1d expression on
CML mDCs. Our study reveals the ROCK-mDC axis as a new potential target to
restore immune surveillance in patients with CML, offering new therapeutic
perspectives for CML treatment. Copyright (c) 2016 Pathological Society of Great
Britain and Ireland. Published by John Wiley & Sons, Ltd.
PMID- 27513301
TI - DNA-PK activity is associated with caspase-dependent myogenic differentiation.
AB - Differentiation of myoblasts into myotubes is essential for skeletal muscle
development and regeneration. Caspase-3 and caspase-9 are required for efficient
myoblast differentiation. The caspase-activated endonuclease activity, CAD, and
the DNA-damage repair protein XRCC1 have also been shown to be required to
complete differentiation. DNA-damage associated with differentiation is
accompanied by phosphorylation of Histone 2AX, an event normally catalysed by
kinases ATR, ATM or DNA-PK. However, the kinase responsible for phosphorylation
during differentiation is not known. Here we show that inhibition of DNA-PK, but
not of ATR or ATM, blocked histone phosphorylation during differentiation. We
also show that DNA-PK inhibition and siRNA-mediated DNA-PK knockdown blocked cell
fusion. These data implicate a new role for DNA-PK in myogenic differentiation.
PMID- 27513303
TI - A subjective utilitarian theory of moral judgment.
AB - Current theories hypothesize that moral judgments are difficult because rational
and emotional decision processes compete. We present a fundamentally different
theory of moral judgment: the Subjective Utilitarian Theory of moral judgment.
The Subjective Utilitarian Theory posits that people try to identify and save the
competing item with the greatest "personal value." Moral judgments become
difficult only when the competing items have similar personal values. In
Experiment 1, we estimate the personal values of 104 items. In Experiments 2-5,
we show that the distributional overlaps of the estimated personal values account
for over 90% of the variance in reaction times (RTs) and response choices in a
moral judgment task. Our model fundamentally restructures our understanding of
moral judgments from a competition between decision processes to a competition
between similarly valued items. (PsycINFO Database Record
PMID- 27513302
TI - A general benevolence dimension that links neural, psychological, economic, and
life-span data on altruistic tendencies.
AB - [Correction Notice: An Erratum for this article was reported in Vol 145(10) of
Journal of Experimental Psychology: General (see record 2016-46925-004). In the
article, there was an error in the Task, Stimuli, and Procedures section. In the
1st sentence in the 6th paragraph, "Following the scanning phase, participants
completed self-report questionnaires meant to reflected the Prosocial Disposition
construct: the agreeableness scale from the Big F, which includes empathic
concern and perspective-taking, and a scale of personality descriptive adjectives
related to altruistic behavior (Wood, Nye, & Saucier, 2010)." should have read:
"Following the scanning phase, participants completed self-report questionnaires
that contained scales to reflect the Prosocial Disposition construct: the Big
Five Inventory (BFI; John et al., 1991), from which we used the agreeableness
scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI;
Davis, 1980), from which we used the empathic concern and perspective-taking
scales; and a scale of personality descriptive adjectives related to altruistic
behavior (Wood, Nye, & Saucier, 2010)."] Individual and life span differences in
charitable giving are an important economic force, yet the underlying motives are
not well understood. In an adult, life span sample, we assessed manifestations of
prosocial tendencies across 3 different measurement domains: (a) psychological
self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural
indicators of "pure altruism." The latter expressed individuals' activity in
neural valuation areas when charities received money compared to when oneself
received money and thus reflected an altruistic concern for others. Results based
both on structural equation modeling and unit-weighted aggregate scores revealed
a strong higher-order General Benevolence dimension that accounted for
variability across all measurement domains. The fact that the neural measures
likely reflect pure altruistic tendencies indicates that General Benevolence is
based on a genuine concern for others. Furthermore, General Benevolence exhibited
a robust increase across the adult life span, potentially providing an
explanation for why older adults typically contribute more to the public good
than young adults.
PMID- 27513304
TI - Bootstrapping agency: How control-relevant information affects motivation.
AB - How does information about one's control over the environment (e.g., having an
own-action effect) influence motivation? The control-based response selection
framework was proposed to predict and explain such findings. Its key tenant is
that control relevant information modulates both the frequency and speed of
responses by determining whether a perceptual event is an outcome of one's
actions or not. To test this framework empirically, the current study examines
whether and how temporal and spatial contiguity/predictability-previously
established as being important for one's sense of agency-modulate motivation from
control. In 5 experiments, participants responded to a cue, potentially
triggering a perceptual effect. Temporal (Experiments 1a-c) and spatial
(Experiments 2a and b) contiguity/predictability between actions and their
potential effects were experimentally manipulated. The influence of these control
relevant factors was measured, both indirectly (through their effect on explicit
judgments of agency) and directly on response time and response frequency. The
pattern of results was highly consistent with the control-based response
selection framework in suggesting that control relevant information reliably
modulates the impact of "having an effect" on different levels of action
selection. We discuss the implications of this study for the notion of motivation
from control and for the empirical work on the sense of agency. (PsycINFO
Database Record
PMID- 27513305
TI - Overcoming approach and withdrawal habits: Approaching former enemies is easier
than withdrawing from former friends.
AB - Both everyday intuition and experimental evidence suggest that habits are
difficult to change. However, despite the abundance of research, it is unknown
whether the ease of habit breaking differs with respect to the most elementary
forms of behavior, approach versus withdrawal. In the present study, we addressed
this question by monitoring the formation and overriding of approach and
withdrawal habits. In an initial habit-formation phase, participants intensely
practiced approach or withdrawal behavior to neutral everyday objects
(Experiments 1) and emotionally laden persons (Experiment 2) until strong
behavioral habits were formed. In a subsequent habit-breaking phase, they were
asked to change their behavior for half of the approach stimuli to withdrawal,
and for half of the withdrawal stimuli to approach. Two intriguing results were
observed. First, the results in the habit-formation phase showed that the
typically observed speed advantage of approach over withdrawal cannot be
diminished by practice. Second, the results in the habit-breaking phase showed
that overriding a withdrawal habit by approach is easier than overriding an
approach habit by withdrawal. In the latter case, participants were more often
caught by their older habit, even when responses were bolstered by appropriate
emotions. Thus, other than reflected in everyday thinking, approaching former
enemies seems to be easier than withdrawing from former friends. (PsycINFO
Database Record
PMID- 27513306
TI - Doing is for feeling.
AB - In 2 experiments we show that preferences can be formed by transfer of valence
from an unconditioned stimulus (US) to an action and then from this valence-laden
action to a novel conditioned stimulus (CS) even though the US and CS were never
presented together. This result expands the approach of intersecting regularities
(Hughes, De Houwer, & Perugini, 2016) to yet another realm of evaluative
learning. In addition, our approach to evaluative learning suggests theoretical
links between the formation of preferences due to actions and general research on
action control. In summary, we discovered an additional route via which humans
may acquire novel preferences and we propose a mental mechanism that may play an
important role in the perceptuomotor system that controls many daily life
behaviors. (PsycINFO Database Record
PMID- 27513307
TI - Mistaking minds and machines: How speech affects dehumanization and
anthropomorphism.
AB - Treating a human mind like a machine is an essential component of dehumanization,
whereas attributing a humanlike mind to a machine is an essential component of
anthropomorphism. Here we tested how a cue closely connected to a person's actual
mental experience-a humanlike voice-affects the likelihood of mistaking a person
for a machine, or a machine for a person. We predicted that paralinguistic cues
in speech are particularly likely to convey the presence of a humanlike mind,
such that removing voice from communication (leaving only text) would increase
the likelihood of mistaking the text's creator for a machine. Conversely, adding
voice to a computer-generated script (resulting in speech) would increase the
likelihood of mistaking the text's creator for a human. Four experiments
confirmed these hypotheses, demonstrating that people are more likely to infer a
human (vs. computer) creator when they hear a voice expressing thoughts than when
they read the same thoughts in text. Adding human visual cues to text (i.e.,
seeing a person perform a script in a subtitled video clip), did not increase the
likelihood of inferring a human creator compared with only reading text,
suggesting that defining features of personhood may be conveyed more clearly in
speech (Experiments 1 and 2). Removing the naturalistic paralinguistic cues that
convey humanlike capacity for thinking and feeling, such as varied pace and
intonation, eliminates the humanizing effect of speech (Experiment 4). We discuss
implications for dehumanizing others through text-based media, and for
anthropomorphizing machines through speech-based media. (PsycINFO Database Record
PMID- 27513308
TI - Discovery of Novel Inhibitors Targeting the Menin-Mixed Lineage Leukemia
Interface Using Pharmacophore- and Docking-Based Virtual Screening.
AB - Disrupting the interaction between mixed lineage leukemia (MLL) fusion protein
and menin provides a therapeutic approach for MLL-mediated leukemia. Here, we aim
to discover novel inhibitors targeting the menin-MLL interface with virtual
screening. Both structure-based molecular docking and ligand-based pharmacophore
models were established, and the models used for compound screening show a
remarkable ability to retrieve known active ligands from decoy molecules.
Verified by a fluorescence polarization assay, five hits with novel scaffolds
were identified. Among them, DCZ_M123 exhibited potent inhibitory activity with
an IC50 of 4.71 +/- 0.12 MUM and a KD of 14.70 +/- 2.13 MUM, and it can
effectively inhibit the human MLL-rearranged leukemia cells MV4;11 and KOPN8 with
GI50 values of 0.84 MUM and 0.54 MUM, respectively.
PMID- 27513309
TI - Static magnetic field induced epigenetic changes in wheat callus.
AB - Deoxyribonucleic acid (DNA) is always damaged by endogenous and exogenous
factors. Magnetic field (MF) is one of these exogenous factors. When repair
mechanisms are not sufficient, mainly because of imbalance in damage or mistakes
in repair mechanisms, methylation of DNA results in polymorphism-related
abnormalities. In this study, low intensity static magnetic field-induced DNA
damage and methylation in wheat calli were investigated by using Random Amplified
Polymorphic DNA and Coupled Restriction Enzyme Digestion-Random Amplification
techniques. Calli were derived from mature embryos of wheat. Both 7- and 14-day
old wheat calli were exposed to 7 mT (millitesla) static MF for 24, 48, 72, 96,
or 120 h of incubation period. The highest change in polymorphism rate was
obtained in calli exposed to 7 mT MF for 120 h in both 7- and 14-day-old calli.
Increase in MF duration caused DNA hypermethylation in both 7- and 14-day-old
calli. Polymorphism and DNA methylation ratio were higher in 7-day-old calli. The
highest methylation level with a value of 25.1% was found in 7-day-old calli
exposed to MF for 120 h. Results suggested that low intensity static magnetic
field may trigger genomic instability and DNA methylation. Bioelectromagnetics.
37:504-511, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27513310
TI - Modulation of growth cone filopodial length by carbon monoxide.
AB - Carbon monoxide (CO) is physiologically produced via heme degradation by heme
oxygenase enzymes. Whereas CO has been identified as an important physiological
signaling molecule, the roles it plays in neuronal development and regeneration
are poorly understood. During these events, growth cones guide axons through a
rich cellular environment to locate target cells and establish synaptic
connections. Previously, we have shown that another gaseous signaling molecule,
nitric oxide (NO), has potent effects on growth cone motility. With NO and CO
sharing similar cellular targets, we wanted to determine whether CO affected
growth cone motility as well. We assessed how CO affected growth cone filopodial
length and determined the signaling pathway by which this effect was mediated.
Using two well-characterized neurons from the freshwater snail, Helisoma
trivolvis, it was found that the CO donor, carbon monoxide releasing molecule-2
(CORM-2), increased filopodial length. CO utilized a signaling pathway that
involved the activation of soluble guanylyl cyclase, protein kinase G, and
ryanodine receptors. While increases in filopodial length often occur from robust
increases in intracellular calcium levels, the timing in which CO increased
filopodial length corresponded with low basal calcium levels in growth cones.
Taken together with findings of a heme oxygenase-like protein in the Helisoma
nervous system, these results provide evidence for CO as a modulator of growth
cone motility and implicate CO as a neuromodulatory signal during neuronal
development and/or regeneration. (c) 2016 Wiley Periodicals, Inc. Develop
Neurobiol 77: 677-690, 2017.
PMID- 27513311
TI - Nimesulide Silver Metallodrugs, Containing the Mitochondriotropic, Triaryl
Derivatives of Pnictogen; Anticancer Activity against Human Breast Cancer Cells.
AB - Novel silver(I) metallo-drugs of the nonsteroidal anti-inflammatory drug
nimesulide (nim) and the mitochondriotropic triaryl derivatives of pnictogen
ligands (tpE, E = P (tpp, tptp, or totp), As (tpAs), Sb (tpSb)) with the formulas
{[Ag(nim) (tpp)2]DMF} (1), [Ag(nim) (tptp)2] (2), [Ag(nim) (totp)] (3), [Ag(nim)
(tpAs)2] (4), and [Ag(nim) (tpSb)3] (5) ((tpp = triphenyphosphine, tptp = tri(p
tolyl)phosphine, totp = tri(o-tolyl)phosphine, tpAs = triphenylarsine, tpSb =
triphenylantimony, and DMF = dimethylformamide) were synthesized and
characterized by melting point, vibrational spectroscopy (mid-Fourier transform
IR), (1)H NMR, UV-visible spectroscopic techniques, and X-ray crystallography.
The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer
cell lines: MCF-7 (estrogen receptor (ER) positive) and MDA-MB-231 (ER negative)
was determined. The genotoxicity on normal human fetal lung fibroblast cells (MRC
5) caused by 1-5 was evaluated by fluorescence microscopy. The absence of
micronucleus in MRC-5 cells confirms the in vitro non toxicity behavior of the
compounds. Because of the morphology of the cells, an apoptotic pathway was
concluded for the cell death. The apoptotic pathway, especially though the
mitochondrion damage, was confirmed by DNA fragmentation, cell cycle arrest, and
permeabilization of the mitochondrial membrane tests. The molecular mechanism of
action of 1-5 was further studied by (i) the binding affinity of 1-5 toward the
calf thymus (CT) DNA, (ii) the inhibitory activity of 1-5 against lipoxygenase
(an enzyme that oxidizes polyunsaturated fatty acids to leukotrienes or
prostaglandins), and (iii) the catalytic activity of 1-5 on the oxidation of
linoleic acid (an acid that partakes in membrane fluidity, membrane enzyme
activities, etc.) to hyperoxolinoleic acid by oxygen.
PMID- 27513314
TI - Pnictogen-Silicon Analogues of Benzene.
AB - Since the discovery of the first "inorganic benzene" (borazine, B3N3H6), the
synthesis of other noncarbon derivatives is an ongoing challenge in Inorganic
Chemistry. Here we report on the synthesis of the first pnictogen-silicon
congeners of benzene, the triarsa- and the triphospha-trisilabenzene
[(PhC(NtBu)2)3Si3E3] (E = P (1a), As (1b)) by a simple metathesis reaction. These
compounds are formed by the reaction of [Cp"2Zr(eta(1:1)-E4)] (E = P, As; Cp" =
C5H3tBu2) with [PhC(NtBu)2SiCl] in toluene at room temperature along with the
silicon pnictogen congeners of the cyclobutadiene, [(PhC(NtBu)2)2Si2E2] (E = P
(2a), As (2b)), which is unprecedented for the arsenic system 2b. All compounds
were comprehensively characterized, and density functional theory calculations
were performed to verify the stability and the aromatic character of the triarsa-
and the triphospha-trisilabenzene.
PMID- 27513312
TI - Chronic Kidney Disease Classification in Systolic Blood Pressure Intervention
Trial: Comparison Using Modification of Diet in Renal Disease and CKD
Epidemiology Collaboration Definitions.
AB - BACKGROUND: Interventional trials have used either the Modification of Diet in
Renal Disease (MDRD) or chronic kidney disease (CKD)-Epidemiology Collaboration
(CKD-EPI) equation for determination of estimated glomerular filtration rate
(eGFR) to define whether participants have stages 3-5 CKD. The equation used to
calculate eGFR may influence the number and characteristics of participants
designated as having CKD. METHODS: We examined the classification of CKD at
baseline using both equations in the Systolic Blood Pressure Intervention Trial
(SPRINT). eGFR was calculated at baseline using fasting serum creatinine values
from a central laboratory. RESULTS: Among 9,308 participants with baseline CKD
classification using the 4-variable MDRD equation specified in the SPRINT
protocol, 681 (7.3%) participants were reclassified to a less advanced CKD stage
(higher eGFR) and 346 (3.7%) were reclassified to a more advanced CKD stage
(lower eGFR) when the CKD-EPI equation was used to calculate eGFR. For eGFRs <90
ml/min/1.73 m2, participants <75 years were more likely to be reclassified to a
less advanced CKD stage; this reclassification was more likely to occur in non
blacks rather than blacks. Participants aged >=75 years were more likely to be
reclassified to a more advanced than a less advanced CKD stage, regardless of
baseline CKD stage. Reclassification of baseline CKD status (eGFR <60 ml/min/1.73
m2) occurred in 3% of participants. CONCLUSIONS: Use of the MDRD equation led to
a higher percentage of participants being classified as having CKD stages 3-4.
Younger and non-black participants were more likely to be reclassified as not
having CKD using the CKD-EPI equation.
PMID- 27513316
TI - Advanced Potential Energy Surfaces for Molecular Simulation.
AB - Advanced potential energy surfaces are defined as theoretical models that
explicitly include many-body effects that transcend the standard fixed-charge,
pairwise-additive paradigm typically used in molecular simulation. However,
several factors relating to their software implementation have precluded their
widespread use in condensed-phase simulations: the computational cost of the
theoretical models, a paucity of approximate models and algorithmic improvements
that can ameliorate their cost, underdeveloped interfaces and limited
dissemination in computational code bases that are widely used in the
computational chemistry community, and software implementations that have not
kept pace with modern high-performance computing (HPC) architectures, such as
multicore CPUs and modern graphics processing units (GPUs). In this Feature
Article we review recent progress made in these areas, including well-defined
polarization approximations and new multipole electrostatic formulations, novel
methods for solving the mutual polarization equations and increasing the MD time
step, combining linear-scaling electronic structure methods with new QM/MM
methods that account for mutual polarization between the two regions, and the
greatly improved software deployment of these models and methods onto GPU and CPU
hardware platforms. We have now approached an era where multipole-based
polarizable force fields can be routinely used to obtain computational results
comparable to state-of-the-art density functional theory while reaching sampling
statistics that are acceptable when compared to that obtained from simpler fixed
partial charge force fields.
PMID- 27513317
TI - Graphene-Based Fluorescence-Quenching-Related Fermi Level Elevation and Electron
Concentration Surge.
AB - Intermolecular p-orbital overlaps in unsaturated pi-conjugated systems, such as
graphene and fluorescent molecules with aromatic structure, serve as the electron
exchanged path. Using Raman-mapping measurements, we observe that the
fluorescence intensity of fluorescein isothiocyanate (FITC) is quenched by
graphene, whereas it persists in graphene-absent substrates (SiO2). After
identifying a mechanism related to photon-induced electron transfer (PET) that
contributes to this fluorescence quenching phenomenon, we validate this mechanism
by conducting analyses on Dirac point shifts of FITC-coated graphene. From these
shifts, Fermi level elevation and the electron-concentration surge in graphene
upon visible-light impingements are acquired. Finally, according to this
mechanism, graphene-based biosensors are fabricated to show the sensing
capability of measuring fluorescently labeled-biomolecule concentrations.
PMID- 27513319
TI - Overexpression of microRNA-497 suppresses cell proliferation and induces
apoptosis through targeting paired box 2 in human ovarian cancer.
AB - MicroRNAs are a class of endogenous, small non-coding RNAs which are tightly
involved in evolution and progression of human cancers. MicroRNA-497 has been
reported as tumor-suppressor in various human cancer. However, the role of miR
497 in ovarian cancer is still poorly known. We investigated the expression level
and cellular function of miR-497 in human ovarian cancer. In this study, the
expression of miR-497 in ovarian cancer tissues and SKOV3 cells was detected by
quantitative reverse-transcription polymerase chain reaction (qRT-PCR). CCK-8
assay was used to analysis the cell proliferation. Transwell assay was performed
to analysis cell migration and invasion. Cell apoptosis was evaluated by flow
cytometry. Luciferase assay was performed to verify a putative target site of miR
497 in the 3'UTR of PAX2 mRNA. The results showed that miR-497 was markedly
decreased in ovarian cancer tissues and SKOV3 cells. Moreover, overexpression of
miR-497 in SKOV3 cells induced PAX2 protein expression and resulted in inhibition
of cell proliferation, migration and invasion, and induction of cell apoptosis.
In addition, we confirmed that PAX2 is a direct target gene of miR-497.
Furthermore, Silencing of PAX2 by RNA interference suppressed cell proliferation
and promoted cell apoptosis in vitro. Taken together, our study rationally
present that miR-497 has a potential role as a useful diagnostic and therapeutic
biomarker for human ovarian cancer.
PMID- 27513321
TI - Qualification of computerized monitoring systems in a cell therapy facility
compliant with the good manufacturing practices.
AB - AIM: Computerized systems (CS) are essential in the development and manufacture
of cell-based medicines and must comply with good manufacturing practice, thus
pushing academic developers to implement methods that are typically found within
pharmaceutical industry environments. MATERIALS & METHODS: Qualitative and
quantitative risk analyses were performed by Ishikawa and Failure Mode and
Effects Analysis, respectively. RESULTS: A process for qualification of a CS that
keeps track of environmental conditions was designed and executed. The simplicity
of the Ishikawa analysis permitted to identify critical parameters that were
subsequently quantified by Failure Mode Effects Analysis, resulting in a list of
test included in the qualification protocols. CONCLUSION: The approach presented
here contributes to simplify and streamline the qualification of CS in compliance
with pharmaceutical quality standards.
PMID- 27513322
TI - Comparative Genomics of the Sigatoka Disease Complex on Banana Suggests a Link
between Parallel Evolutionary Changes in Pseudocercospora fijiensis and
Pseudocercospora eumusae and Increased Virulence on the Banana Host.
AB - The Sigatoka disease complex, caused by the closely-related Dothideomycete fungi
Pseudocercospora musae (yellow sigatoka), Pseudocercospora eumusae (eumusae leaf
spot), and Pseudocercospora fijiensis (black sigatoka), is currently the most
devastating disease on banana worldwide. The three species emerged on bananas
from a recent common ancestor and show clear differences in virulence, with P.
eumusae and P. fijiensis considered the most aggressive. In order to understand
the genomic modifications associated with shifts in the species virulence spectra
after speciation, and to identify their pathogenic core that can be exploited in
disease management programs, we have sequenced and analyzed the genomes of P.
eumusae and P. musae and compared them with the available genome sequence of P.
fijiensis. Comparative analysis of genome architectures revealed significant
differences in genome size, mainly due to different rates of LTR retrotransposon
proliferation. Still, gene counts remained relatively equal and in the range of
other Dothideomycetes. Phylogenetic reconstruction based on a set of 46 conserved
single-copy genes strongly supported an earlier evolutionary radiation of P.
fijiensis from P. musae and P. eumusae. However, pairwise analyses of gene
content indicated that the more virulent P. eumusae and P. fijiensis share
complementary patterns of expansions and contractions in core gene families
related to metabolism and enzymatic degradation of plant cell walls, suggesting
that the evolution of virulence in these two pathogens has, to some extent, been
facilitated by convergent changes in metabolic pathways associated with nutrient
acquisition and assimilation. In spite of their common ancestry and shared host
specificity, the three species retain fairly dissimilar repertoires of effector
proteins, suggesting that they likely evolved different strategies for
manipulating the host immune system. Finally, 234 gene families, including seven
putative effectors, were exclusively present in the three Sigatoka species, and
could thus be related to adaptation to the banana host.
PMID- 27513323
TI - Early Sexual Intercourse: Prospective Associations with Adolescents Physical
Activity and Screen Time.
AB - OBJECTIVES: To assess the prospective associations of physical activity behaviors
and screen time with early sexual intercourse initiation (i.e., before 15 years)
in a large sample of adolescents. METHODS: We used two waves of data from the
Rotterdam Youth Monitor, a longitudinal study conducted in the Netherlands. The
analysis sample consisted of 2,141 adolescents aged 12 to 14 years (mean age at
baseline = 12.2 years, SD = 0.43). Physical activity (e.g., sports outside
school), screen time (e.g., computer use), and early sexual intercourse
initiation were assessed by means of self-report questionnaires. Logistic
regression models were tested to assess the associations of physical activity
behaviors and screen time (separately and simultaneously) with early sexual
intercourse initiation, controlling for confounders (i.e., socio-demographics and
substance use). Interaction effects with gender were tested to assess whether
these associations differed significantly between boys and girls. RESULTS: The
only physical activity behavior that was a significant predictor of early sexual
intercourse initiation was sports club membership. Adolescent boys and girls who
were members of a sports club) were more likely to have had early sex (OR = 2.17;
95% CI = 1.33, 3.56. Significant gender interaction effects indicated that boys
who watched TV >=2 hours/day (OR = 2.00; 95% CI = 1.08, 3.68) and girls who used
the computer >=2 hours/day (OR = 3.92; 95% CI = 1.76, 8.69) were also
significantly more likely to have engaged in early sex. CONCLUSION: These
findings have implications for professionals in general pediatric healthcare,
sexual health educators, policy makers, and parents, who should be aware of these
possible prospective links between sports club membership, TV watching (for
boys), and computer use (for girls), and early sexual intercourse initiation.
However, continued research on determinants of adolescents' early sexual
initiation is needed to further contribute to the strategies for improving
adolescents' healthy sexual development and behaviors.
PMID- 27513324
TI - Life with Bacterial Secretion Systems.
PMID- 27513325
TI - Health-care provider communication with expectant parents during a prenatal
diagnosis: an integrative review.
AB - The pregnancy and health-care experience of expectant parents who receive a
prenatal diagnosis of their unborn infant is distinctively fraught with
uncertainty. Health-care providers (HCPs) that care for parents during this
uncertain time have an exceptional opportunity to positively impact parental
outcomes. An integrative literature review was conducted to explore HCPs' impact
on parents' experiences of receiving a prenatal diagnosis. Thirty-three articles
met study inclusion criteria (n=18 qualitative; 6 quantitative; 9 mixed methods).
HCP communication was the major theme identified, because of its overarching
impact on parents' experiences of receiving a prenatal diagnosis of their unborn
infant. Parents' perception of the information communicated to them about their
unborn infant's diagnosis by their HCP, and the manner in which that information
is communicated to them, affects parents' ability to cope with the diagnosis.
Recommendations for health-care delivery models, and for future research are
discussed.
PMID- 27513326
TI - Electronic communication preferences among mothers in the neonatal intensive care
unit.
AB - OBJECTIVE: Mobile communication with the medical-care team has the potential to
decrease stress among parents of infants admitted to the neonatal intensive care
unit (NICU). We assessed mobile use and communication preferences in a population
of urban minority NICU mothers. STUDY DESIGN: A 30-question English language
survey was administered to mothers of NICU patients. RESULTS: The survey was
completed by 217 mothers, 75% were Black, and 75% reported annual household
income below $20 000. Only 56% had a computer with Internet access at home, but
79% used smartphones. Most (79%) have searched the Internet for health
information in the past year. Receiving electronic messages about their babies
was viewed favorably, and text messaging was the preferred platform. The majority
of mothers felt electronic messaging would improve communication but should not
replace verbal communication. CONCLUSION: Mobile communication is used widely in
this population of NICU mothers and could potentially improve provider-parent
communication and reduce parental stress.
PMID- 27513327
TI - The state of point-of-care ultrasonography use and training in neonatal-perinatal
medicine and pediatric critical care medicine fellowship programs.
AB - OBJECTIVE: The current state of point-of-care ultrasonography (POCUS) use and
education in neonatal-perinatal medicine (NPM) and pediatric critical care
medicine (PCCM) is unknown. Our aim was to quantify POCUS use, training and
perceptions regarding education and barriers among the United States NPM and PCCM
fellowship programs. STUDY DESIGN: A 14-question survey was emailed to the
fellowship directors of all the United States NPM and PCCM fellowship programs.
RESULTS: The response rate was 55% (52/95) and 59% (39/66) for NPM and PCCM
programs, respectively. Over 90% of respondents in both groups believe that
fellows and attendings should receive POCUS training. PCCM programs, compared
with NPM, had greater access to POCUS machines (97% vs 63%, P<0.001), and more
often used POCUS for diagnoses and management (76% vs 29%, P<0.001) and
procedural guidance (95% vs 37%, P<0.001). The most common indications were
cardiac/hemodynamics, pulmonary pathology and vascular access in both
specialties. PCCM reported more training to fellows (90% vs 29%, P<0.001). Both
group perceived lack of time to learn, lack of equipment/funds, liability
concerns, lack of personnel to train physicians and cardiology/radiology
resistance as significant barriers to POCUS implementation. CONCLUSIONS: Both NPM
and PCCM fellowship programs believe in the benefits of POCUS and that their
physicians should receive the necessary training. Compared with PCCM, NPM
fellowships programs have less access to POCUS machines and less frequently use
POCUS and train their fellows and attendings. There remain significant barriers
to utilization of POCUS, especially in NPM.
PMID- 27513328
TI - Disparities in Depressive Symptoms and Antidepressant Treatment by Gender and
Race/Ethnicity among People Living with HIV in the United States.
AB - OBJECTIVE: To describe disparities along the depression treatment cascade, from
indication for antidepressant treatment to effective treatment, in HIV-infected
individuals by gender and race/ethnicity. METHODS: The Center for AIDS Research
(CFAR) Network of Integrated Clinical Systems (CNICS) cohort includes 31,000 HIV
infected adults in routine clinical care at 8 sites. Individuals were included in
the analysis if they had a depressive symptoms measure within one month of
establishing HIV care at a CNICS site. Depressive symptoms were measured using
the validated Patient Health Questionnaire-9 (PHQ-9). Indication for
antidepressant treatment was defined as PHQ-9 >= 10 or a current antidepressant
prescription. Antidepressant treatment was defined as a current antidepressant
prescription. Evidence-based antidepressant treatment was considered treatment
changes based on a person's most recent PHQ-9, in accordance with clinical
guidelines. We calculated the cumulative probability of moving through the
depression treatment cascade within 24 months of entering CNICS HIV care. We used
multivariable Cox proportional hazards models to estimate associations between
gender, race/ethnicity, and a range of depression outcomes. RESULTS: In our
cohort of HIV-infected adults in routine care, 47% had an indication for
antidepressant treatment. Significant drop-offs along the depression treatment
cascade were seen for the entire study sample. However, important disparities
existed. Women were more likely to have an indication for antidepressant
treatment (HR 1.54; 95% CI 1.34, 1.78), receive antidepressant treatment (HR
2.03; 95% CI 1.53, 2.69) and receive evidence-based antidepressant treatment (HR
1.67; 95% CI 1.03, 2.74), even after accounting for race/ethnicity. Black non
Hispanics (HR 0.47, 95% CI 0.35, 0.65), Hispanics (HR 0.63, 95% CI 0.44, 0.89)
and other race/ethnicities (HR 0.35, 95% CI 0.17, 0.73) were less likely to
initiate antidepressant treatment, compared to white non-Hispanics. CONCLUSIONS:
In our cohort of HIV-infected adults depressive symptoms were common. Important
disparities in the prevalence of depressive symptoms and receipt of
antidepressant treatment existed by gender and race/ethnicity.
PMID- 27513330
TI - Are Price Limits Effective? An Examination of an Artificial Stock Market.
AB - We investigated the inter-day effects of price limits policies that are employed
in agent-based simulations. To isolate the impact of price limits from the impact
of other factors, we built an artificial stock market with higher frequency price
limits hitting. The trading mechanisms in this market are the same as the trading
mechanisms in China's stock market. Then, we designed a series of simulations
with and without price limits policy. The results of these simulations
demonstrate that both upper and lower price limits can cause a volatility
spillover effect and a trading interference effect. The process of price
discovery will be delayed if upper price limits are imposed on a stock market;
however, this phenomenon does not occur when lower price limits are imposed.
PMID- 27513329
TI - Differential Expression Pattern of THBS1 and THBS2 in Lung Cancer: Clinical
Outcome and a Systematic-Analysis of Microarray Databases.
AB - Thrombospondin 1 and thrombospondin 2 (THBS1 and THBS2) share similar
multifunctional domains, and are known to be antiangiogenic. However, the
expression pattern of THBS1 and THBS2 is different, and the specific role of
THBS2 in different subtypes of lung cancer remains largely unclear. To evaluate
the significance of THBS1 and THBS2 in the development of lung cancer, the
present study performed a microarray-based systematic-analysis to determine the
transcript levels of thrombospondins and their relation to the prognosis in lung
cancer. THBS1 was in general underexpressed in lung cancer; in contrast, mRNA
levels of THBS2 were markedly overexpressed in a number of datasets of non-small
cell lung carcinoma (NSCLC), including lung adenocarcinoma (AC) and squamous cell
carcinoma. Similar expression pattern of THBS1 and THBS2 was verified in
pulmonary AC cell lines with real-time PCR analysis. The survival of lung AC
patients with high THBS2 mRNA expression levels was poorer than patients with low
levels of expression of THBS2. In a microarray-based analysis, genes coexpressed
with THBS1 or THBS2 were determined. Pulmonary AC patients with a high expression
level of sevenTSHB1-coexpressed genes (CCL5, CDH11, FYB, GZMK, LA-DQA1, PDE4DIP,
and SELL) had better survival rates than those with a low expression level.
Patients with a high expression of seven TSHB2-coexpressed genes (CHI3L1, COL5A2,
COL11A1, FAP, MXRA5, THY1, and VCAN) had poor survival rates. Downregulation of
VCAN and THBS2 with shRNA inhibited the cell proliferation in the A549 cell line.
In summary, THBS1 functions as a tumor suppressor in lung adenocarcinoma.
However, THBS2 may play a double-edged role in the progression of lung AC, i.e.
anti-angiogenic and oncogenic function. Further study on the mechanism underlying
the activity of THBS2 is warranted to have further implications for cancer
diagnosis and treatment of pulmonary AC.
PMID- 27513331
TI - Home-Based and Facility-Based Directly Observed Therapy of Tuberculosis Treatment
under Programmatic Conditions in Urban Tanzania.
AB - INTRODUCTION: Decentralization of Directly Observed Treatment (DOT) for
tuberculosis (TB) to the community (home-based DOT) has improved the coverage of
TB treatment and reduced the burden to the health care facilities (facility-based
DOT). We aimed to compare TB treatment outcomes in home-based and facility-based
DOT under programmatic conditions in an urban setting with a high TB burden.
METHODOLOGY: A retrospective analysis of a cohort of adult TB patients (>=15
years) routinely notified between 2010 and 2013 in two representative TB sub
districts in the Temeke district, Dar es Salaam, Tanzania. We assessed
differences in treatment outcomes by calculating Risk Ratios (RRs). We used
logistic regression to assess the association between DOT and treatment outcomes.
RESULTS: Data of 4,835 adult TB patients were analyzed, with a median age of 35
years, 2,943 (60.9%) were men and TB/HIV co-infection prevalence of 39.9%. A
total of 3,593 (74.3%) patients were treated under home-based DOT. Patients on
home-based DOT were more likely to die compared to patients on facility-based DOT
(RR 2.04, 95% Confidence Interval [95% CI]: 1.52-2.73), and more likely to
complete TB treatment (RR 1.14, 95% CI: 1.06-1.23), but less likely to have a
successful treatment outcome (RR 0.94, 95% CI: 0.92-0.97). Home-based DOT was
preferred by women (adjusted Odds Ratio [aOR] 1.55, 95% CI: 1.34-1.80, p<0.001),
older people (aOR 1.01 for each year increase, 95% CI: 1.00-1.02, p = 0.001) and
patients with extra-pulmonary TB (aOR 1.45, 95% CI: 1.16-1.81, p = 0.001), but
less frequently by patients on a retreatment regimen (aOR 0.12, 95% CI: 0.08
0.19, p<0.001). CONCLUSIONS/SIGNIFICANCE: TB patients under home-based DOT had
more frequently risk factors of death such as older age, HIV infection and sputum
smear-negative TB, and had higher mortality compared to patients under facility
based DOT. Further operational research is needed to monitor the implementation
of DOT under programmatic conditions.
PMID- 27513332
TI - Anti-Vascular Endothelial Growth Factor Antibody Suppresses ERK and NF-kappaB
Activation in Ischemia-Reperfusion Lung Injury.
AB - Ischemia-reperfusion (IR)-induced acute lung injury (ALI) is implicated in
several clinical conditions like lung transplantation, acute pulmonary embolism
after thrombolytic therapy, re-expansion of collapsed lung from pneumothorax or
pleural effusion, cardiopulmonary bypass and etc. Because mortality remains high
despite advanced medical care, prevention and treatment are important clinical
issues for IR-induced ALI. Vascular endothelial growth factor (VEGF) has a
controversial role in ALI. We therefore conducted this study to determine the
effects of anti-VEGF antibody in IR-induced ALI. In the current study, the IR
induced ALI was conducted in a rat model of isolated-perfused lung in situ in the
chest. The animals were divided into the control, control + preconditioning anti
VEGF antibody (bevacizumab, 5mg/kg), IR, IR + preconditioning anti-VEGF antibody
(1mg/kg), IR+ preconditioning anti-VEGF antibody (5mg/kg) and IR+ post-IR anti
VEGF antibody (5mg/kg) group. There were eight adult male Sprague-Dawley rats in
each group. The IR caused significant pulmonary micro-vascular hyper
permeability, pulmonary edema, neutrophilic infiltration in lung tissues,
increased tumor necrosis factor-alpha, and total protein concentrations in
bronchoalveolar lavage fluid. VEGF and extracellular signal-regulated kinase
(ERK) were increased in IR-induced ALI. Administration of preconditioning anti
VEGF antibody significantly suppressed the VEGF and ERK expressions and
attenuated the IR-induced lung injury. This study demonstrates the important role
of VEGF in early IR-induced ALI. The beneficial effects of preconditioning anti
VEGF antibody in IR-induced ALI include the attenuation of lung injury, pro
inflammatory cytokines, and neutrophilic infiltration into the lung tissues.
PMID- 27513333
TI - An Activity Index for Raw Accelerometry Data and Its Comparison with Other
Activity Metrics.
AB - Accelerometers have been widely deployed in public health studies in recent
years. While they collect high-resolution acceleration signals (e.g., 10-100 Hz),
research has mainly focused on summarized metrics provided by accelerometers
manufactures, such as the activity count (AC) by ActiGraph or Actical. Such
measures do not have a publicly available formula, lack a straightforward
interpretation, and can vary by software implementation or hardware type. To
address these problems, we propose the physical activity index (AI), a new metric
for summarizing raw tri-axial accelerometry data. We compared this metric with
the AC and another recently proposed metric for raw data, Euclidean Norm Minus
One (ENMO), against energy expenditure. The comparison was conducted using data
from the Objective Physical Activity and Cardiovascular Health Study, in which
194 women 60-91 years performed 9 lifestyle activities in the laboratory, wearing
a tri-axial accelerometer (ActiGraph GT3X+) on the hip set to 30 Hz and an Oxycon
portable calorimeter, to record both tri-axial acceleration time series
(converted into AI, AC, and ENMO) and oxygen uptake during each activity
(converted into metabolic equivalents (METs)) at the same time. Receiver
operating characteristic analyses indicated that both AI and ENMO were more
sensitive to moderate and vigorous physical activities than AC, while AI was more
sensitive to sedentary and light activities than ENMO. AI had the highest
coefficients of determination for METs (0.72) and was a better classifier of
physical activity intensity than both AC (for all intensity levels) and ENMO (for
sedentary and light intensity). The proposed AI provides a novel and transparent
way to summarize densely sampled raw accelerometry data, and may serve as an
alternative to AC. The AI's largely improved sensitivity on sedentary and light
activities over AC and ENMO further demonstrate its advantage in studies with
older adults.
PMID- 27513334
TI - Are virus-induced cancers more sensitive to checkpoint inhibitors?
PMID- 27513335
TI - Collective Behavior of Market Participants during Abrupt Stock Price Changes.
AB - Under uncertainty, human and animal collectives often respond stochastically to
events they encounter. Human or animal individuals behave depending on others'
actions, and sometimes follow choices that are sub-optimal for individuals. Such
mimetic behaviors are enhanced during emergencies, creating collective behavior
of a group. A stock market that is about to crash, as markets did immediately
after the Lehman Brothers bankruptcy, provides illustrative examples of such
behaviors. We provide empirical evidence proving the existence of collective
behavior among stock market participants in emergent situations. We investigated
the resolution of extreme supply-and-demand order imbalances by increased
balancing counter orders: buy and sell orders for excess supply and demand
respectively, during times of price adjustment, so-called special quotes on the
Tokyo Stock Exchange. Counter orders increase positively depending on the
quantity of revealed counter orders: the accumulated orders in the book until
then. Statistics of the coming counter order are well described using a logistic
regression model with the ratio of revealed orders until then to the finally
revealed orders as the explanatory variable. Results given here show that the
market participants make Bayesian estimations of optimal choices to ascertain
whether to order using information about orders of other participants.
PMID- 27513336
TI - Assessing and Managing the Current and Future Pest Risk from Water Hyacinth,
(Eichhornia crassipes), an Invasive Aquatic Plant Threatening the Environment and
Water Security.
AB - Understanding and managing the biological invasion threats posed by aquatic
plants under current and future climates is a growing challenge for biosecurity
and land management agencies worldwide. Eichhornia crassipes is one of the
world's worst aquatic weeds. Presently, it threatens aquatic ecosystems, and
hinders the management and delivery of freshwater services in both developed and
developing parts of the world. A niche model was fitted using CLIMEX, to estimate
the potential distribution of E. crassipes under historical and future climate
scenarios. Under two future greenhouse gas emission scenarios for 2080 simulated
with three Global Climate Models, the area with a favourable temperature regime
appears set to shift polewards. The greatest potential for future range expansion
lies in Europe. Elsewhere in the northern hemisphere temperature gradients are
too steep for significant geographical range expansion under the climate
scenarios explored here. In the Southern Hemisphere, the southern range boundary
for E. crassipes is set to expand southwards in Argentina, Australia and New
Zealand; under current climate conditions it is already able to invade the
southern limits of Africa. The opportunity exists to prevent its spread into the
islands of Tasmania in Australia and the South Island of New Zealand, both of
which depend upon hydroelectric facilities that would be threatened by the
presence of E. crassipes. In Europe, efforts to slow or stop the spread of E.
crassipes will face the challenge of limited internal biosecurity capacity. The
modelling technique demonstrated here is the first application of niche modelling
for an aquatic weed under historical and projected future climates. It provides
biosecurity agencies with a spatial tool to foresee and manage the emerging
invasion threats in a manner that can be included in the international standard
for pest risk assessments. It should also support more detailed local and
regional management.
PMID- 27513337
TI - The Dual NOD1/NOD2 Agonism of Muropeptides Containing a Meso-Diaminopimelic Acid
Residue.
AB - Muropeptides are fragments of peptidoglycan that trigger innate immune responses
by activating nucleotide-binding oligomerization domain (NOD) 1 and NOD2.
Muropeptides from Gram-negative bacteria contain a meso-diaminopimelic acid (meso
DAP) residue in either a terminal or a non-terminal position. While the former
ones are known to be recognized by NOD1, much less is known about recognition of
muropeptides with non-terminal meso-DAP, which are most abundant moieties of Gram
negative peptidoglycans. Here, we developed a novel system to assess biological
activity of muropeptides, based on CRISPR/Cas9-mediated knockout (KO) of NOD1 and
NOD2 genes in modified HEK293T cells. Using NOD1/NOD2 knockout and overexpression
systems, as well as human monocytes and macrophages, we refine the current view
of muropeptide recognition. We show that NOD2 can recognize different natural
muropeptides containing a meso-DAP residue (preferably in a non-terminal
position), provided they are present at micromolar concentrations. NOD2 accepts
muropeptides with long and branched peptide chains and requires an intact N
acetylmuramyl residue. Muropeptides with non-terminal meso-DAP can activate NOD1
as well, but, in this case, probably require peptidase pre-processing to expose
the meso-DAP residue. Depending on NOD1/NOD2 ratio in specific cell types, meso
DAP-containing muropeptides can be recognized either primarily via NOD2 (in
monocytes) or via NOD1 (in monocyte-derived macrophages and HEK293T-derived
cells). The dual NOD1/NOD2 agonism of meso-DAP-containing muropeptides should be
taken into account when assessing cellular responses to muropeptides and
designing muropeptide immunostimulants and vaccine adjuvants.
PMID- 27513340
TI - Silver nanoparticle functionalized glass fibers for combined surface-enhanced
Raman scattering spectroscopy (SERS)/surface-assisted laser desorption/ionization
(SALDI) mass spectrometry via plasmonic/thermal hot spots.
AB - We presented the fabrication of a silver nanoparticle (Ag NP) functionalized
glass fiber (Ag-GF) substrate for combined surface-enhanced Raman scattering
spectroscopy (SERS)/surface-assisted laser desorption/ionization (SALDI) mass
spectrometry. Ag NPs were immobilized onto the surface of glass fibers through a
simple sputter deposition process. The SERS and SALDI activities strongly
depended on the nanostructures of the deposited Ag NPs on the GFs. The closely
packed Ag NPs with a size of 20-50 nm and an inter-particle nanoscale gap of less
than 10 nm were effective for the simultaneously enhanced SERS/SALDI substrate
via plasmonic/thermal "hot spots", while the interconnected continuous Ag film
reduced both the SERS/SALDI activities. The SERS enhanced factor (EFSERS) and
SALDI enhanced factor (EFSALDI) were newly proposed. Finally, the concentration
dependent signal intensities of SERS and SALD-MS of sulfur compounds using an
identical Ag NP-GF substrate were examined, and the linear dependence
relationship in the log-log plot was demonstrated for the combined quantitative
SERS/SALDI-MS analysis.
PMID- 27513339
TI - The Effect of Protandim(r) Supplementation on Athletic Performance and Oxidative
Blood Markers in Runners.
AB - The purpose of this study determined if oral supplementation of Protandim(r) (a
nutraceutical) for 90 days improved 5-km running performance and reduced serum
thiobarbituric acid-reacting substances (TBARS) at rest, an indicator of
oxidative stress. Secondary objectives were to measure whole blood superoxide
dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPX), at rest and
10 minutes after completion of the race before and after supplementation as well
as quality of life. In a double-blind, randomized, placebo controlled trial, 38
runners [mean (SD) = 34 (7) yrs; BMI = 22 (2) kg/m2] received either 90 days of
Protandim(r) [1 pill a day, n = 19)] or placebo (n = 19). Randomization was done
in blocks of two controlling for sex and 5-km baseline performance. A 5-km race
was performed at baseline and after 90 days of supplementation, with blood
samples taken before and 10-min after each race. Fasting blood samples were
acquired at baseline, after 30, 60, and 90 days of supplementation. TBARS, SOD,
GPX, and GSH were assayed in an out-of-state accredited lab. Running performance
was not altered by Protandim(r) or placebo [20.3 (2.1) minutes, with an -8 (33)
seconds change in 5-km time regardless of group]. There was no change in TBARS,
SOD, or GPX (at rest) after three months of Protandim(r) supplementation compared
to placebo. However, in a subgroup >= 35 years of age, there was a 2-fold higher
increase in SOD in those taking Protandim(r) for three months compared to those
on placebo (p = 0.038). The mean post-race change in TBARS (compared to pre-race)
increased by about 20% in half of the subjects, but was not altered between
groups, even after three months of supplementation. Quality of life was also not
different between the two conditions. In conclusion, Protandim(r) did not (1)
alter 5-km running time, (2) lower TBARS at rest (3) raise antioxidant enzyme
concentrations compared to placebo (with exception of SOD in those >= 35 years
old) or, (4) affect quality of life compared to placebo. TRIAL REGISTRATION:
ClinicalTrials.gov NCT02172625.
PMID- 27513338
TI - A Public Database of Memory and Naive B-Cell Receptor Sequences.
AB - The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the
recognition of, and response to, a wide range of epitopes, but this diversity has
also limited our understanding of humoral immunity. We present a public database
of more than 37 million unique BCR sequences from three healthy adult donors that
is many fold deeper than any existing resource, together with a set of online
tools designed to facilitate the visualization and analysis of the annotated
data. We estimate the clonal diversity of the naive and memory B-cell repertoires
of healthy individuals, and provide a set of examples that illustrate the utility
of the database, including several views of the basic properties of
immunoglobulin heavy chain sequences, such as rearrangement length, subunit
usage, and somatic hypermutation positions and dynamics.
PMID- 27513342
TI - Allopolyploid Origin of Chenopodium album s. str. (Chenopodiaceae): A Molecular
and Cytogenetic Insight.
AB - Reticulate evolution is characterized by occasional hybridization between two
species, creating a network of closely related taxa below and at the species
level. In the present research, we aimed to verify the hypothesis of the
allopolyploid origin of hexaploid C. album s. str., identify its putative parents
and estimate the frequency of allopolyploidization events. We sampled 122
individuals of the C. album aggregate, covering most of its distribution range in
Eurasia. Our samples included putative progenitors of C. album s. str. of both
ploidy levels, i.e. diploids (C. ficifolium, C. suecicum) and tetraploids (C.
striatiforme, C. strictum). To fulfil these objectives, we analysed sequence
variation in the nrDNA ITS region and the rpl32-trnL intergenic spacer of cpDNA
and performed genomic in-situ hybridization (GISH). Our study confirms the
allohexaploid origin of C. album s. str. Analysis of cpDNA revealed tetraploids
as the maternal species. In most accessions of hexaploid C. album s. str., ITS
sequences were completely or nearly completely homogenized towards the tetraploid
maternal ribotype; a tetraploid species therefore served as one genome donor.
GISH revealed a strong hybridization signal on the same eighteen chromosomes of
C. album s. str. with both diploid species C. ficifolium and C. suecicum. The
second genome donor was therefore a diploid species. Moreover, some individuals
with completely unhomogenized ITS sequences were found. Thus, hexaploid
individuals of C. album s. str. with ITS sequences homogenized to different
degrees may represent hybrids of different ages. This proves the existence of at
least two different allopolyploid lineages, indicating a polyphyletic origin of
C. album s. str.
PMID- 27513341
TI - FmvB: A Francisella tularensis Magnesium-Responsive Outer Membrane Protein that
Plays a Role in Virulence.
AB - Francisella tularensis is the causative agent of the lethal disease tularemia.
Despite decades of research, little is understood about why F. tularensis is so
virulent. Bacterial outer membrane proteins (OMPs) are involved in various
virulence processes, including protein secretion, host cell attachment, and
intracellular survival. Many pathogenic bacteria require metals for intracellular
survival and OMPs often play important roles in metal uptake. Previous studies
identified three F. tularensis OMPs that play roles in iron acquisition. In this
study, we examined two previously uncharacterized proteins, FTT0267 (named fmvA,
for Francisella metal and virulence) and FTT0602c (fmvB), which are homologs of
the previously studied F. tularensis iron acquisition genes and are predicted
OMPs. To study the potential roles of FmvA and FmvB in metal acquisition and
virulence, we first examined fmvA and fmvB expression following pulmonary
infection of mice, finding that fmvB was upregulated up to 5-fold during F.
tularensis infection of mice. Despite sequence homology to previously
characterized iron-acquisition genes, FmvA and FmvB do not appear to be involved
iron uptake, as neither fmvA nor fmvB were upregulated in iron-limiting media and
neither DeltafmvA nor DeltafmvB exhibited growth defects in iron limitation.
However, when other metals were examined in this study, magnesium-limitation
significantly induced fmvB expression, DeltafmvB was found to express
significantly higher levels of lipopolysaccharide (LPS) in magnesium-limiting
medium, and increased numbers of surface protrusions were observed on DeltafmvB
in magnesium-limiting medium, compared to wild-type F. tularensis grown in
magnesium-limiting medium. RNA sequencing analysis of DeltafmvB revealed the
potential mechanism for increased LPS expression, as LPS synthesis genes kdtA and
wbtA were significantly upregulated in DeltafmvB, compared with wild-type F.
tularensis. To provide further evidence for the potential role of FmvB in
magnesium uptake, we demonstrated that FmvB was outer membrane-localized.
Finally, DeltafmvB was found to be attenuated in mice and cytokine analyses
revealed that DeltafmvB-infected mice produced lower levels of pro-inflammatory
cytokines, including GM-CSF, IL-3, and IL-10, compared with mice infected with
wild-type F. tularensis. Taken together, although the function of FmvA remains
unknown, FmvB appears to play a role in magnesium uptake and F. tularensis
virulence. These results may provide new insights into the importance of
magnesium for intracellular pathogens.
PMID- 27513343
TI - Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated
Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart.
AB - Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells
in vertebrate development. To what extent PDGFs also exert beneficial homeostatic
or reparative roles in adult organs, as opposed to adverse fibrogenic responses
in pathology, are unclear. PDGF signaling plays critical roles during heart
development, during which forced overexpression of PDGFs induces detrimental
cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct
myocardial repair. Different PDGFs may exert different effects mediated through
the two PDGF receptors (PDGFRalpha and PDGFRbeta) in different cell types. Here,
we assessed responses induced by five known PDGF isoforms in the adult mouse
heart in the context of adenovirus vector-mediated inflammation. Our results show
that different PDGFs have different, in some cases even opposing, effects.
Strikingly, whereas the major PDGFRalpha agonists (PDGF-A and -C) decreased the
amount of scar tissue and increased the numbers of PDGFRalpha-positive
fibroblasts, PDGFRbeta agonists either induced large scars with extensive
inflammation (PDGF-B) or dampened the adenovirus-induced inflammation and
produced a small and dense scar (PDGF-D). These results provide evidence for PDGF
isoform-specific inflammation-modulating functions that may have therapeutic
implications. They also illustrate a surprising complexity in the PDGF-mediated
pathophysiological responses.
PMID- 27513344
TI - Efficacy and Safety of Topical Pidobenzone 4% as Adjuvant Treatment for Solar
Lentigines: Result of a Randomized, Controlled, Clinical Trial.
AB - BACKGROUND/OBJECTIVE: This study aims at the evaluation of the efficacy and
safety of a combination therapy based on pidobenzone 4% and fractional CO2 laser
or cryotherapy in the treatment of solar lentigines and the prevention of
eventual posttreatment hyperchromia. METHODS: Efficacy was clinically evaluated
by grading the pigmentation level with the Skin Tone Color Scale (STCS), and by
grading patients' impression through a Visual Analog Scale (VAS). RESULTS: Our
study shows that the associated treatment was safe and that it improves the
therapeutic results on solar lentigines and prevents postiatrogenic
hyperpigmentation compared with physical therapy alone. CONCLUSION: The
combination of cryotherapy and pidobenzone 4% has been found to be the most
useful treatment.
PMID- 27513345
TI - Ingenol Mebutate vs. Daylight Photodynamic Therapy in a Kidney Transplant
Recipient.
AB - We present the case of a 73-year-old male patient who had received a first renal
transplant at 36 years and a second one at the age of 55 years. He is currently
under immunosuppression with everolimus 2.5 mg/day and prednisone 5 mg/day. The
patient presented with multiple actinic keratoses on both cheeks and the forehead
and received treatment by ingenol mebutate 150 ug/g gel daily on 3 consecutive
days on his right cheek and methyl aminolevulinate (MAL) photodynamic therapy
activated by daylight (MAL-dPDT) on the forehead and the left cheek. MAL-dPDT
treatment proved a feasible, repeatable, physician-directed method of treating
field cancerization with limited morbidity for a period of 6 days. Treatment with
ingenol mebutate gel was a feasible, possibly self-directed method of treating
field cancerization with limited morbidity for 10 days in this immunosuppressed
patient. Both treatments showed similar efficacy. At the time of treatment, the
MAL daylight PDT ran at 3 times the cost of ingenol mebutate gel.
PMID- 27513346
TI - Therapists' Inadequate Feelings and Long-Term Effect of Transference Work.
PMID- 27513347
TI - Cervical cancer: Screening, management, and prevention.
AB - Cervical cancer incidence in the United States is estimated to affect 12,900
women in 2016, with 4,100 deaths. Screening for this cancer with Pap test and
adjunct human papillomavirus testing has made cervical cancer a treatable
disease. This article reviews screening, treatment recommendations, and
prevention for cervical cancer.
PMID- 27513348
TI - Mitochondrial genome association study with peripheral arterial disease and
venous thromboembolism.
AB - BACKGROUND AND AIMS: Peripheral arterial disease (PAD) and venous thromboembolism
(VTE) are vascular traits sharing common modifiable and non-modifiable risk
factors. These vascular pathologies have known nuclear-encoded genetic risk
factors and the mitochondrial DNA may account for part of the missing
heritability. To determine if PAD and VTE have a dual genetic control
(mitochondrial and nuclear), we hereby investigated the association of
mitochondrial DNA polymorphisms and haplogroups with these vascular traits.
METHODS: The association of mitochondrial single nucleotide polymorphisms
(mtSNPs) and haplogroups was tested in 1652 PAD cases and 1629 controls from the
eMERGE PAD genome-wide association study (GWAS), and 1241 VTE cases and 1278
controls from the GENEVA GWAS of venous thrombosis (dbGaP accession numbers
phs000203.v1.p1 and phs000289.v2.p1, respectively). RESULTS: 66 and 72 mtSNPs
passed quality control filters and were tested for association with PAD and VTE,
respectively. Significant evidence of population stratification could not be
detected in both datasets. Three mtSNPs (m.477T > C, m.9667A > G, and m.10915T >
C) were nominally associated (3.01 * 10(-3) <= pa <= 3.96 * 10(-2)) with PAD in
the logistic regression adjusted for confounding factors, and m.11914G > A was
nominally associated (pa = 4.14 * 10(-2)) with VTE. None of the nine major
mitochondrial haplogroups were associated with either PAD or VTE. CONCLUSION:
Unlike other vascular diseases such as stroke and diabetes, these results suggest
that common mitochondrial variants individually or in combination do not play a
major role in PAD and VTE susceptibility.
PMID- 27513349
TI - Bisphosphonates for cardiovascular risk reduction: A systematic review and meta
analysis.
AB - BACKGROUND AND AIMS: Bisphosphonates might be effective in reducing
cardiovascular events due to their ability to reduce calcification in arterial
walls. We aimed to investigate the effects of treatment with bisphosphonates on
the prevention of atherosclerotic processes and cardiovascular disease. METHODS:
Pubmed, Embase and the Cochrane Library were systematically reviewed by two
independent investigators for randomized controlled studies published up to
January 2016, in which the effect of bisphosphonates on arterial wall disease,
cardiovascular events, cardiovascular mortality or all-cause mortality were
reported. There was no restriction for the type of population used in the trials.
Random-effects models were used to calculate the pooled estimates. RESULTS: 61
trials reporting the effects of bisphosphonates on the outcomes of interest were
included. Bisphosphonates had beneficial effects on arterial wall disease
regarding arterial calcification (pooled mean percentage difference of 2 trials
11.52 (95% CI -16.51 to -6.52, p < 0.01, I(2) 13%), but not on arterial stiffness
(pooled mean percentage difference of 2 trials -2.82; 95% CI -10.71-5.07; p =
0.48, I(2) 59%). No effect of bisphosphonate treatment on cardiovascular events
was found (pooled RR of 20 trials 1.03; 95% CI 0.91-1.17, I(2) 16%), while a
lower risk for cardiovascular mortality was observed in patients treated with
bisphosphonates (pooled RR of 10 trials 0.81; 95% CI 0.64-1.02; I(2) 0%) although
not statistically significant. Patients treated with bisphosphonates had a
reduced risk of all-cause mortality (pooled RR of 48 trials 0.90; 95% CI 0.84
0.98; I(2) 53%). CONCLUSIONS: In this systematic review and meta-analysis it is
shown that bisphosphonates reduce arterial wall calcification but have no effect
on arterial stiffness or on cardiovascular events. Bisphosphonates tend to reduce
the risk of cardiovascular mortality and reduce all-cause mortality in various
patient groups, including osteoporosis and cancer patients.
PMID- 27513350
TI - Outbreak of Plague in a High Malaria Endemic Region - Nyimba District, Zambia,
March-May 2015.
AB - Outbreaks of plague have been recognized in Zambia since 1917 (1). On April 10,
2015, Zambia's Ministry of Health was notified by the Eastern Provincial Medical
Office of possible bubonic plague cases in Nyimba District. Eleven patients with
acute fever and cervical lymphadenopathy had been evaluated at two rural health
centers during March 28-April 9, 2015; three patients died. To confirm the
outbreak and develop control measures, the Zambia Ministry of Health's Field
Epidemiology Training Program (ZFETP) conducted epidemiologic and laboratory
investigations in partnership with the University of Zambia's schools of Medicine
and Veterinary Medicine and the provincial and district medical offices. Twenty
one patients with clinically compatible plague were identified, with symptom
onset during March 26-May 5, 2015. The median age was 8 years, and all patients
were from the same village. Blood specimens or lymph node aspirates from six
(29%) patients tested positive for Yersinia pestis by polymerase chain reaction
(PCR). There is an urgent need to improve early identification and treatment of
plague cases. PCR is a potential complementary tool for identifying plague,
especially in areas with limited microbiologic capacity. Twelve (57%) patients,
including all six with PCR-positive plague and all three who died, also tested
positive for malaria by rapid diagnostic test (RDT). Plague patients coinfected
with malaria might be misdiagnosed as solely having malaria, and appropriate
antibacterial treatment to combat plague might not be given, increasing risk for
mortality. Because patients with malaria might be coinfected with other
pathogens, broad spectrum antibiotic treatment to cover other pathogens is
recommended for all children with severe malaria, until a bacterial infection is
excluded.
PMID- 27513351
TI - First Introduction of Two Australian Temnocephalan Species into Africa with an
Alien Host: Double Trouble.
AB - The redclaw crayfish, Cherax quadricarinatus (Decapoda: Parastacidae), is native
to Australia but has been introduced to South Africa as a warm-water aquaculture
species. In a South African natural waterbody, examined crayfish had high
intensity infections of 3 temnocephalan species on their body surfaces and within
the branchial chambers. Temnocephalans were characterized using light and
scanning electron microscopy and identified as Craspedella pedum, Diceratocephala
boschmai, and Didymorchis sp. This is the first report of the introduction of
Australian temnocephalans, C. pedum and Didymorchis sp., to Africa and expands
the known distribution of these species beyond their presumptive native range.
The present study also documents a naturalized population of C. quadricarinatus
from a natural water body in South Africa, comprising a new geographical locality
record.
PMID- 27513352
TI - Life satisfaction in women with epilepsy during and after pregnancy.
AB - OBJECTIVE: The aim of this study was to investigate life satisfaction in women
with epilepsy during and after pregnancy. METHODS: The study was based on the
Norwegian Mother and Child Cohort Study, including 102,265 women with and without
epilepsy from the general population. Investigation took place at pregnancy weeks
15-19 and 6 and 18months postpartum. Women with epilepsy were compared with a
reference group without epilepsy. RESULTS: The proportion of women with epilepsy
was 0.6-0.7% at all three time points. Women with epilepsy reported lower life
satisfaction and self-esteem both during and after pregnancy compared with the
references. Single parenting correlated negatively with life satisfaction in
epilepsy during the whole study period. Epilepsy was associated with lower levels
of relationship satisfaction and higher levels of work strain during pregnancy
and lower levels of self-efficacy and satisfactory somatic health 18months
postpartum. Adverse life events, such as divorce, were more common in women with
epilepsy compared with the references, and fewer women with epilepsy had a paid
job 18months postpartum. SIGNIFICANCE: Reduced life satisfaction associated with
epilepsy during and after pregnancy showed that, even in a highly developed
welfare society, women with epilepsy struggle. Mothers with epilepsy and their
partners should be examined for emotional complaints and partnership satisfaction
during and after pregnancy. Validated screening tools are available for such
measures.
PMID- 27513353
TI - Japanese nursing students' sense of belonging: A story of Uchi (insider) and Soto
(outsider).
AB - Clinical placement experiences are the cornerstone of nursing education and a
body of literature indicates that belongingness is fundamental to students'
learning when undertaking placements. However, little is known about Japanese
nursing students' sense of belonging and how it is influenced by their cultural
values. The aim of this paper is to profile a study that: measured the extent to
which Japanese nursing students' experience a sense of belonging in clinical
placements, and explored the factors that impact on and are consequences of that
experience. A mixed methods design was used with quantitative data collected
using the Belongingness Scale-Clinical Placement Experience and qualitative data
collected using semi-structured interviews. Ninety-two third and fourth year
students from a large regional university in Japan completed the questionnaire;
of these six also participated in interviews. The results identified similarities
and differences between this and other studies of belongingness. Supportive and
welcoming clinical environments facilitated participants' belongingness and
motivation to learn. However, the belongingness scores of this sample were lower
than those in all other studies. This may be explained, in part, by the Japanese
cultural values of "Uchi (insider) and Soto" (outsider), which pervaded the
participants' placement experiences and led to feelings of exclusion and
alienation.
PMID- 27513354
TI - Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for
Death and New Disability.
AB - OBJECTIVES: The prevalence of septic acute kidney injury and impact on functional
status of PICU survivors are unknown. We used data from an international
prospective severe sepsis study to elucidate functional outcomes of children
suffering septic acute kidney injury. DESIGN: Secondary analysis of patients in
the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute
kidney injury was defined on the study day using Kidney Disease Improving Global
Outcomes definitions. Patients with no acute kidney injury or stage 1 acute
kidney injury ("no/mild acute kidney injury") were compared with those with stage
2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome
was a composite of death or new moderate disability at discharge defined as a
Pediatric Overall Performance Category score of 3 or higher and increased by 1
from baseline. SETTING: One hundred twenty-eight PICUs in 26 countries. PATIENTS:
Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies
study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two (21%)
of 493 patients had severe acute kidney injury. More than twice as many patients
with severe acute kidney injury died or developed new moderate disability
compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001).
Severe acute kidney injury was independently associated with death or new
moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after
adjustment for age, region, baseline disability, malignancy, invasive mechanical
ventilation, albumin administration, and the pediatric logistic organ dysfunction
score. CONCLUSIONS: In a multinational cohort of critically ill children with
severe sepsis and high mortality rates, septic acute kidney injury is
independently associated with further increased death or new disability.
PMID- 27513355
TI - Neuromuscular Recovery Is Prolonged After Immobilization or Superimposition of
Inflammation With Immobilization Compared to Inflammation Alone: Data From a
Preclinical Model.
AB - OBJECTIVES: Recovery from ICU-acquired muscle weakness extends beyond hospital
stay. We hypothesized that immobilization, more than inflammation, plays a
prominent role in the delayed recovery from critical illness. DESIGN:
Prospective, randomized, controlled, experimental study. SETTING: Animal
laboratory, university hospital. SUBJECTS: Male Sprague-Dawley rats.
INTERVENTIONS: Animals were divided to have one hind limb immobilized (n = 129)
or sham-immobilized (n = 129) on day -12. After surgery, rats were further
assigned to two subgroups. To induce inflammation, rats received three IV
injections of Corynebacterium parvum on days -12, -8, and -4. Controls received
saline at the respective time-points. At day 0, the limbs were remobilized and
recovery from inflammation and/or immobilization was followed for 36 days.
MEASUREMENTS AND MAIN RESULTS: At day 0 and after 4, 12, or 36 days of recovery,
maximum tetanic tension and tetanic fade (functional parameters = primary outcome
variables) as well as nicotinic acetylcholine receptor expression, muscle mass,
and histologic changes (structural parameters = secondary outcome variables) were
measured. Impaired maximum tetanic tension, decreased tibialis muscle mass, and
fiber diameter due to inflammation alone recovered by day 4. Tetanic fade was not
affected by inflammation. Immobilization-induced loss of tibialis muscle mass,
decreased fiber diameter, and tetanic fade did not return to normal until day 36,
while maximum tetanic tension had recovered at that time. In the presence of
inflammation and immobilization, the decrease in tibialis muscle mass, fiber
diameter, and maximum tetanic tension, as well as decreased tetanic fade
persisted until day 36. Up-regulation of nicotinic acetylcholine receptors
normalized before day 4 following inflammation, but persisted until day 4
following immobilization. CONCLUSIONS: In our model, muscle function and
structure recovered from inflammation within 4-12 days. Immobilization-induced
neuromuscular changes, however, persisted even at day 36, especially if
inflammation was concomitant.
PMID- 27513356
TI - Incidence and Characteristics of Ventilator-Associated Events Reported to the
National Healthcare Safety Network in 2014.
AB - OBJECTIVE: Ventilator-associated event surveillance was introduced in the
National Healthcare Safety Network in 2013, replacing surveillance for ventilator
associated pneumonia in adult inpatient locations. We determined incidence rates
and characteristics of ventilator-associated events reported to the National
Healthcare Safety Network. DESIGN, SETTING, AND PATIENTS: We analyzed data
reported from U.S. healthcare facilities for ventilator-associated events that
occurred in 2014, the first year during which ventilator-associated event
surveillance definitions were stable. We used negative binomial regression
modeling to identify healthcare facility and inpatient location characteristics
associated with ventilator-associated events. We calculated ventilator-associated
event incidence rates, rate distributions, and ventilator utilization ratios in
critical care and noncritical care locations and described event characteristics.
MEASUREMENTS AND MAIN RESULTS: A total of 1,824 healthcare facilities reported
32,772 location months of ventilator-associated event surveillance data to the
National Healthcare Safety Network in 2014. Critical care unit pooled mean
ventilator-associated event incidence rates ranged from 2.00 to 11.79 per 1,000
ventilator days, whereas noncritical care unit rates ranged from 0 to 14.86 per
1,000 ventilator days. The pooled mean proportion of ventilator-associated events
defined as infection-related varied from 15.38% to 47.62% in critical care units.
Pooled mean ventilator utilization ratios in critical care units ranged from 0.24
to 0.47. CONCLUSIONS: We found substantial variability in ventilator-associated
event incidence, proportions of ventilator-associated events characterized as
infection-related, and ventilator utilization within and among location types.
More work is needed to understand the preventable fraction of ventilator
associated events and identify patient care strategies that reduce ventilator
associated events.
PMID- 27513357
TI - Carbon Monoxide Improves Efficacy of Mesenchymal Stromal Cells During Sepsis by
Production of Specialized Proresolving Lipid Mediators.
AB - OBJECTIVES: Mesenchymal stromal cells are being investigated as a cell-based
therapy for a number of disease processes, with promising results in animal
models of systemic inflammation and sepsis. Studies are ongoing to determine ways
to further improve the therapeutic potential of mesenchymal stromal cells. A gas
molecule that improves outcome in experimental sepsis is carbon monoxide. We
hypothesized that preconditioning of mesenchymal stromal cells with carbon
monoxide ex vivo would promote further therapeutic benefit when cells are
administered in vivo after the onset of polymicrobial sepsis in mice. DESIGN:
Animal study and primary cell culture. SETTING: Laboratory investigation.
SUBJECTS: BALB/c mice. INTERVENTIONS: Polymicrobial sepsis was induced by cecal
ligation and puncture. Mesenchymal stromal cells, mesenchymal stromal cells
conditioned with carbon monoxide, fibroblasts, or fibroblasts-conditioned with
carbon monoxide were delivered by tail vein injections to septic mice. The mice
were assessed for survival, bacterial clearance, and the inflammatory response
during sepsis in each of the groups. Mesenchymal stromal cells were also assessed
for their ability to promote bacterial phagocytosis by neutrophils, the
production of specialized proresolving lipid mediators, and their importance for
mesenchymal stromal cells function using gene silencing. MEASUREMENTS AND MAIN
RESULTS: Ex vivo preconditioning with carbon monoxide allowed mesenchymal stromal
cells to be administered later after the onset of sepsis (6 hr), and yet maintain
their therapeutic effect with increased survival. Carbon monoxide preconditioned
mesenchymal stromal cells were also able to alleviate organ injury, improve
bacterial clearance, and promote the resolution of inflammation. Mesenchymal
stromal cells exposed to carbon monoxide, with docosahexaenoic acid substrate,
produced specialized proresolving lipid mediators, particularly D-series
resolvins, which promoted survival. Silencing of lipoxygenase pathways (5
lipoxygenase and 12/15-lipoxygenase), which are important enzymes for specialized
proresolving lipid mediator biosynthesis, resulted in a loss of therapeutic
benefit bestowed on mesenchymal stromal cells by carbon monoxide. CONCLUSIONS:
Taken together, these data suggest that production of specialized proresolving
lipid mediators contribute to improved mesenchymal stromal cell efficacy when
exposed to carbon monoxide, resulting in an improved therapeutic response during
sepsis.
PMID- 27513358
TI - Lung Injury Prediction Score in Hospitalized Patients at Risk of Acute
Respiratory Distress Syndrome.
AB - OBJECTIVE: The Lung Injury Prediction Score identifies patients at risk for acute
respiratory distress syndrome in the emergency department, but it has not been
validated in non-emergency department hospitalized patients. We aimed to evaluate
whether Lung Injury Prediction Score identifies non-emergency department
hospitalized patients at risk of developing acute respiratory distress syndrome
at the time of critical care contact. DESIGN: Retrospective study. SETTING: Five
academic medical centers. PATIENTS: Nine hundred consecutive patients (>= 18 yr
old) with at least one acute respiratory distress syndrome risk factor at the
time of critical care contact. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: Lung Injury Prediction Score was calculated using the worst values
within the 12 hours before initial critical care contact. Patients with acute
respiratory distress syndrome at the time of initial contact were excluded. Acute
respiratory distress syndrome developed in 124 patients (13.7%) a median of 2
days (interquartile range, 2-3) after critical care contact. Hospital mortality
was 22% and was significantly higher in acute respiratory distress syndrome than
non-acute respiratory distress syndrome patients (48% vs 18%; p < 0.001).
Increasing Lung Injury Prediction Score was significantly associated with
development of acute respiratory distress syndrome (odds ratio, 1.31; 95% CI,
1.21-1.42) and the composite outcome of acute respiratory distress syndrome or
death (odds ratio, 1.26; 95% CI, 1.18-1.34). A Lung Injury Prediction Score
greater than or equal to 4 was associated with the development of acute
respiratory distress syndrome (odds ratio, 4.17; 95% CI, 2.26-7.72), composite
outcome of acute respiratory distress syndrome or death (odds ratio, 2.43; 95%
CI, 1.68-3.49), and acute respiratory distress syndrome after accounting for the
competing risk of death (hazard ratio, 3.71; 95% CI, 2.05-6.72). For acute
respiratory distress syndrome development, the Lung Injury Prediction Score has
an area under the receiver operating characteristic curve of 0.70 and a Lung
Injury Prediction Score greater than or equal to 4 has 90% sensitivity (misses
only 10% of acute respiratory distress syndrome cases), 31% specificity, 17%
positive predictive value, and 95% negative predictive value. CONCLUSIONS: In a
cohort of non-emergency department hospitalized patients, the Lung Injury
Prediction Score and Lung Injury Prediction Score greater than or equal to 4 can
identify patients at increased risk of acute respiratory distress syndrome and/or
death at the time of critical care contact but it does not perform as well as in
the original emergency department cohort.
PMID- 27513359
TI - Age-Dependent Changes in the Pulmonary Renin-Angiotensin System Are Associated
With Severity of Lung Injury in a Model of Acute Lung Injury in Rats.
AB - OBJECTIVES: A growing body of evidence suggests that age affects the main
pathophysiologic mechanisms of the acute respiratory distress syndrome. This may
imply the need for developing age-tailored therapies for acute respiratory
distress syndrome. However, underlying molecular mechanisms governing age-related
susceptibility first need to be unraveled. In a rat model of acute lung injury,
we investigated whether age affects the balance between the two key enzymes of
the pulmonary renin-angiotensin system, angiotensin-converting enzyme, and
angiotensin-converting enzyme 2. We hypothesized that aging shifts the balance
toward the lung injury-promoting angiotensin-converting enzyme, which may form an
explanation for the differences in severity of lung injury between different age
groups. DESIGN: Prospective, randomized controlled animal study. SETTING:
University medical research laboratory. SUBJECTS: Infant (15 +/- 2 d), juvenile
(37 +/- 2 d), adult (4 +/- 0.2 mo), and elderly (19.5 +/- 0.5 mo) male RCCHan
Wistar rats. INTERVENTIONS: Lung injury was induced by intratracheal
administration of lipopolysaccharide (5 mg/kg) and 4 hours of mechanical
ventilation (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: In lipopolysaccharide
exposed and mechanical ventilated rats, angiotensin-converting enzyme activity in
bronchoalveolar lavage fluid increased 3.2-fold in elderly when compared with
infants. No changes in bronchoalveolar lavage fluid angiotensin-converting enzyme
2 activity were found. In addition, membrane-bound angiotensin-converting enzyme
activity decreased. Together with the presence of angiotensin-converting enzyme
sheddase ADAM9 (a disintegrin and metalloproteinase domain-containing protein 9)
and an age-dependent increase in tumor necrosis factor-alpha, an activator of
ADAM9, these results indicate increased shedding of angiotensin-converting enzyme
in the alveolar compartment, thereby shifting the balance toward the injurious
pathway. This imbalance was associated with an increased inflammatory mediator
response and more lung injury (wet-to-dry ratio and histology) in elderly rats.
CONCLUSIONS: Increasing age is associated with an imbalance of the pulmonary
renin-angiotensin system, which correlates with aggravated inflammation and more
lung injury. These changes might form the ground for new therapeutic strategies
in terms of dosing and effectiveness of renin-angiotensin system-modulating
agents for treatment of acute respiratory distress syndrome.
PMID- 27513360
TI - Dimensions and Role-Specific Mediators of Surrogate Trust in the ICU.
AB - OBJECTIVE: In the ICU, discussions between clinicians and surrogate decision
makers are often accompanied by conflict about a patient's prognosis or care
plan. Trust plays a role in limiting conflict, but little is known about the
determinants of trust in the ICU. We sought to identify the dimensions of trust
and clinician behaviors conducive to trust formation in the ICU. DESIGN:
Prospective qualitative study. SETTING: Medical ICU of a major urban university
hospital. SUBJECTS: Surrogate decision makers of intubated, mechanically
ventilated patients in the medical ICU. MEASUREMENTS AND MAIN RESULTS:
Semistructured interviews focused on surrogates' general experiences in the ICU
and on their trust in the clinicians caring for the patient. Interviews were
audio-recorded, transcribed verbatim, and coded by two reviewers. Constant
comparison was used to identify themes pertaining to trust. Thirty surrogate
interviews revealed five dimensions of trust in ICU clinicians: technical
competence, communication, honesty, benevolence, and interpersonal skills. Most
surrogates emphasized the role of nurses in trust formation, frequently citing
their technical competence. Trust in physicians was most commonly related to
honesty and the quality of their communication with surrogates. CONCLUSIONS:
Interventions to improve trust in the ICU should be role-specific, since
surrogate expectations are different for physicians and nurses with regard to
behaviors relevant to trust. Further research is needed to confirm our findings
and explore the impact of trust modification on clinician-family conflict.
PMID- 27513361
TI - Bone Marrow-Derived Endothelial Progenitor Cells Reduce Recurrent Miscarriage in
Gestation.
AB - Bone marrow-derived endothelial progenitor cells (EPCs) have been shown to
contribute to not only angiogenesis in ischemic tissue but also
neovascularization in uterine endometrium formation. Reduced neovascularization
and elevation of serum soluble Flt1, a functional blockage of VEGF, in the
development of placenta is thought to be one of the major causes of repeated
miscarriages in gestation. We then examined whether transfusion of VEGF
expressing extrinsic EPCs prevented frequent miscarriage via its promotional
effect on neovascularization with a VEGFeNOS signaling pathway in a mouse
miscarriage model. The results showed that systemic EPC transfusion significantly
reduced the rate of miscarriage, and EPCs were frequently observed in the
miscarriage placenta. In contrast, only a few EPCs were detected in the placenta
of normal gestation. The vascular pattern was irregular, and vessel size was
small in the miscarriage placenta compared with that of normal gestation. The
placental vascular pattern in miscarriage tended to be normalized with increased
vessel size up to a similar level as normal gestation by EPC recruitment. For the
mechanistic insight, since soluble Flt1 inhibits EPC functions, it was suggested
that the increased soluble Flt1 could suppress the recruited EPC functional
activity in the miscarriage placenta. In vitro experiments by soluble Flt1
treatment in cultured EPCs suggested that the vascular abnormality could be
partly due to the inhibition of eNOS expression by the increased amounts of
soluble Flt1. These findings from animal experiments indicated that autologous
EPC therapy may be a novel therapy to prevent miscarriage in high-risk
pregnancies, such as preeclampsia.
PMID- 27513362
TI - The retrieval and selection of arithmetic facts in oral arithmetic.
AB - We examined the co-activation and the selection of arithmetic facts in oral
arithmetic. In two experiments, participants had to verify whether simple
additions were correct or not. In Experiment 1, additions were presented in the
auditory-verbal format; in Experiment 2, additions were presented in the digit
format but simulating the temporal sequence of auditory problems of Experiment 1.
Results were similar in both experiments. Firstly, participants took the same
time to respond when an addition was incorrect but the result was that of
multiplying the operands (e.g., 2+4=8) relative to a control addition with
unrelated result. Secondly, participants took more time to respond when the
result of multiplying the operands of the first trial was presented again in a
correct addition problem (e.g., 2+6=8) relative to a control addition. This
pattern of results is discussed in terms of the temporal resolution to which
auditory problems are resolved and the role of an inhibitory mechanism involved
in the selection of arithmetic facts.
PMID- 27513364
TI - Total Synthesis of Nuclear Factor of Activated T-Cells-68 (NFAT-68): Sequential
Use of Chiral Allenylsilane and Titanium Alkoxide-Mediated Reductive Coupling
Bond Construction.
AB - Highly enantioenriched chiral allenylsilanes 4 were prepared in high yield
through a scalable synthetic sequence, employing a modified copper-catalyzed SN2'
reaction. These reagents were used for the production of enantioenriched
homoproparglylic ethers 5, which were subjected to titanium alkoxide-mediated
reductive coupling with acetylenic esters to produce (E,E)-dienes 6 bearing
alpha,beta,gamma,delta-unsaturated esters. Both enantiomers of nuclear factor of
activated T-cells-68 (NFAT-68) were synthesized in five steps with the sequential
use of the two methods.
PMID- 27513363
TI - The From Survivor to Thriver program: RCT of an online therapist-facilitated
program for rape-related PTSD.
AB - This study evaluated the efficacy of the From Survivor to Thriver program, an
interactive, online therapist-facilitated cognitive-behavioral program for rape
related PTSD. Eighty-seven college women with rape-related PTSD were randomized
to complete the interactive program (n=46) or a psycho-educational self-help
website (n=41). Both programs led to large reductions in interview-assessed PTSD
at post-treatment (interactive d=2.22, psycho-educational d=1.10), which were
maintained at three month follow-up. Both also led to medium- to large-sized
reductions in self-reported depressive and general anxiety symptoms. Follow-up
analyses supported that the therapist-facilitated interactive program led to
superior outcomes among those with higher pre-treatment PTSD whereas the psycho
educational self-help website led to superior outcomes for individuals with lower
pre-treatment PTSD. Future research should examine the efficacy and effectiveness
of online interventions for rape-related PTSD including whether treatment
intensity matching could be utilized to maximize outcomes and therapist resource
efficiency.
PMID- 27513365
TI - Identification of five novel arginine vasopressin gene mutations in patients with
familial neurohypophyseal diabetes insipidus.
AB - Familial neurohypophyseal diabetes insipidus (FNDI) is a genetic disorder
presenting with polyuria and polydipsia and is caused by mutations in the
arginine vasopressin-neurophysin II (AVP-NPII) gene. The clinical manifestations
of this disorder vary greatly depending on different mutations. The present study
reports the genetic, clinical and biochemical characteristics of patients with
FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and
four individual cases diagnosed with FNDI were included. Biochemical markers and
magnetic resonance imaging (MRI) were evaluated and genomic DNA was sequenced.
The results revealed that age at onset ranged from 1.0 to 11.0 years. Daily urine
volumes ranged from 2.0 to 12.0 liters. One patient had mental retardation and
three patients had puberty retardation; one patient had nausea, vomiting and
mental retardation; and two patients had fever. Treatments, if given, included
desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high
intensity signals were absent in two cases and present in four cases. Sequencing
revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of
the present study indicate that FNDI exhibits different clinical manifestations
and a diverse age at onset. Posterior pituitary MRI does not provide a definite
diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an
enhanced understanding of FNDI pathogenesis may provide a basis for the
development of presymptomatic FNDI diagnotic tools.
PMID- 27513366
TI - Monomeric and dimeric Al(iii) complexes for the production of polylactide.
AB - A series of monometallic and bimetallic Al(iii) complexes with substituted
naphthyl based Schiff base ligands have been prepared and characterised. When 1
aminonaphthalene based ligands were reacted with AlMe3 monometallic complexes
were isolated, however, with 1,5 and 1,8-diaminonaphthalene based ligands
bimetallic complexes were formed. In all cases 4-coordinate tetrahedral Al(iii)
centres were observed in the solid state and in solution. There was little
difference in rate of polymerisation of rac-lactide between the monometallic and
bimetallic complexes based on 1,5-diaminonaphthalene. However, for the 1,8
diaminonaphthalene the complex was an order of magnitude faster than the
monometallic and the analogous 1,5-system. Moreover, this complex was active at
room temperature, which is rare for aluminium initiators, and PLA with a high
degree (Pm = 0.82) of isotacticity was observed.
PMID- 27513367
TI - Dynamic Contrast-Enhanced Computed Tomography-Derived Blood Volume and Blood Flow
Correlate With Patient Outcome in Metastatic Renal Cell Carcinoma.
AB - OBJECTIVES: The aim was to explore the potential for using dynamic contrast
enhanced computed tomography as a noninvasive functional imaging biomarker before
and during the early treatment of metastatic renal cell carcinoma (mRCC).
MATERIALS AND METHODS: Dynamic contrast-enhanced computed tomography scans were
performed at baseline and after 5 and 10 weeks' treatment in 69 prospectively
included mRCC patients receiving treatment with interferon alpha and interleukin
2 (n = 26); interferon alpha, interleukin 2, and bevacizumab (n = 24); sunitinib
(n = 7); pazopanib (n = 5); or temsirolimus (n = 7). Using a prototype software
program (Advanced Perfusion and Permeability Application, Philips Healthcare,
Best, the Netherlands), blood volume (BV), blood flow (BF), and permeability
surface area product (PS) were calculated for each tumor at baseline, week 5, and
week 10. These parameters as well as relative changes between baseline and weeks
5 and 10 were tested for associations with progression-free survival (PFS) and
overall survival (OS) using Kaplan-Meier curves and log-rank tests. RESULTS:
Using the 25th percentile as the cutoff, baseline BV for all patients independent
of subsequent treatment was statistically significantly associated with PFS (10.8
vs 5.3 months, P = 0.007) and OS (35.2 vs 13.3 months, P = 0.001), and baseline
BF was significantly associated with OS (31.7 vs 14.6 months, P = 0.024) with
high values for both parameters being associated with significantly longer PFS
and OS. Baseline PS was not associated with PFS or OS.In patients treated with
angiogenesis inhibitors (bevacizumab, sunitinib, pazopanib, or temsirolimus), the
relative change in BV from baseline to week 5 using 25th percentile as the cutoff
was associated with PFS (5.6 vs 24.8 months, P = 0.001) and OS (19.1 months vs
not reached, P = 0.008) and from baseline to week 10 with PFS (8.1 vs 16.4
months, P = 0.014) and OS (15.5 months vs not reached, P = 0.002). The relative
change in BF from baseline to week 5 using medians as the cutoff was associated
with PFS (5.5 vs 14.3 months, P = 0.018) and OS (14.6 vs 31.7 months, P = 0.027).
The relative change in BF from baseline to week 10 using 25th percentile as the
cutoff was associated with PFS (8.3 vs 46.9 months, P = 0.011) and OS (19.1 vs
53.0 months, P = 0.006). For both parameters, the largest reductions during early
treatment were associated with increased PFS and OS.In patients receiving
immunotherapy only (interferon alpha and interleukin 2), relative changes in PS
between baseline and weeks 5 and 10 were significantly associated with PFS with
larger increases associated with longer PFS. In patients receiving angiogenesis
inhibitors, the relative changes in PS between baseline and week 10 were
significantly associated with PFS and OS with larger reductions associated with
favorable outcomes. CONCLUSIONS: In patients with mRCC treated with angiogenesis
inhibitors, the largest reductions in BV and BF between baseline and weeks 5 and
10 were associated with favorable outcomes. At baseline, the lowest BV and BF
were associated with the poorest outcomes regardless of the subsequent treatment.
Early reductions in PS were associated with favorable outcomes for those treated
with angiogenesis inhibitors and with poor outcomes for those treated with
immunotherapies.
PMID- 27513369
TI - Alteration of sex hormone levels and steroidogenic pathway by several low
molecular weight phthalates and their metabolites in male zebrafish (Danio rerio)
and/or human adrenal cell (H295R) line.
AB - Low molecular weight phthalates, such as diethyl phthalate (DEP), benzyl butyl
phthalate (BBzP), or diisobutyl phthalate (DiBP), are suspected to disrupt
endocrine system. However, their adverse effects on sex steroid hormones and
underlying mechanisms are not well-documented. The aim of this study is to
investigate the effects of major low molecular weight phthalates (LMWPs), i.e.,
DEP, BBzP, and DiBP, and their hydrolytic metabolites, on sex steroid hormone
system, employing male zebrafish and/or a human adrenocortical carcinoma (H295R)
cell. In male zebrafish, 14-day exposure to DEP, BBzP, or DiBP significantly
decreased testosterone (T) concentrations. All test compounds significantly up
regulated cyp19a gene expression, and down-regulated star and 3beta hsd genes in
the male fish. In H295R cell, all test compounds except monoisobutyl phthalate
(MiBP) reduced T concentrations and increased E2/T ratio. Gene expression changes
in H295R cell, e.g., significant down-regulation of StAR gene and up-regulation
of CYP19A gene, supported depressed synthesis of sex hormones in the adrenal
cell. Our results show that not only DEP, BBzP, and DiBP, but also their
hydrolytic metabolites disrupt sex hormone balances through modulating key
steroidogenic genes in the human adrenal cells and in zebrafish.
PMID- 27513370
TI - Kinetic study of time-dependent fixation of UVI on biochar.
AB - Biochar, a by-product from the production of biofuel and syngas by gasification,
was tested as a material for adsorption and fixation of UVI from aqueous
solutions. A batch experiment was conducted to study the factors that influence
the adsorption and time-dependent fixation on biochar at 20 degrees C, including
pH, initial concentration of UVI and contact time. Uranium (UVI) adsorption was
highly dependent on pH but adsorption on biochar was high over a wide range of pH
values, from 4.5 to 9.0, and adsorption strength was time-dependent over several
days. The experimental data for pH>7 were most effectively modelled using a
Freundlich adsorption isotherm coupled to a reversible first order kinetic
equation to describe the time-dependent fixation of UVI within the biochar
structure. Desorption experiments showed that UVI was only sparingly desorbable
from the biochar with time and isotopic dilution with 233UVI confirmed the low,
or time-dependent, lability of adsorbed 238UVI. Below pH 7 the adsorption
isotherm trend suggested precipitation, rather than true adsorption, may occur.
However, across all pH values (4.5-9) measured saturation indices suggested
precipitation was possible: autunite below pH 6.5 and either swartzite, liebigite
or bayleyite above pH 6.5.
PMID- 27513368
TI - Lung Function Trajectory in Bronchiolitis Obliterans Syndrome after Allogeneic
Hematopoietic Cell Transplant.
AB - RATIONALE: The natural history of lung function in patients with bronchiolitis
obliterans syndrome (BOS) after allogeneic hematopoietic cell transplant is
poorly characterized. Understanding the trajectory of lung function is necessary
for prompt clinical recognition and treatment and also for the rational design of
prospective studies. OBJECTIVES: To describe the longitudinal trajectory of lung
function parameters, including FEV1, in patients with BOS after hematopoietic
cell transplant. METHODS: Subjects with BOS defined by National Institutes of
Health consensus guidelines criteria from a recent multicenter prospective trial
of combination treatment with fluticasone, azithromycin and montelukast and a
retrospective cohort from Fred Hutchinson Cancer Research Center were included.
Longitudinal change in FEV1 for each patient was calculated on the basis of
available pulmonary function tests in three periods: pre-BOS, from BOS diagnosis
to 6 months, and 6-18 months after diagnosis. The effect of treatment on FEV1
trajectory was analyzed by univariate and multivariate linear regression. The
Kaplan-Meier method was used to estimate survival. MEASUREMENTS AND MAIN RESULTS:
The FEV1 percent predicted value at diagnosis was 46% (interquartile range, 35
57%) for trial participants and 53% (interquartile range, 41-64%) for the
retrospective cohort. There was a concomitant mild reduction in FVC, as well as a
marked reduction in forced expiratory flow, midexpiratory phase, at diagnosis.
While there was individual heterogeneity, the overall FEV1 trajectory was
characterized by a marked decline within 6 months prior to BOS diagnosis,
followed by stability of FEV1 early after diagnosis and a slow rate of decline
beyond 6 months. The effect of the trial medications on FEV1 trajectory after BOS
diagnosis was a mean rate of change of 0.92% predicted per month (95% confidence
interval, -0.53 to 2.37) compared with the retrospective cohort, but this was not
statistically significant. Two-year overall survival rates were 76% and 72% for
the study participants and the retrospective cohort patients, respectively.
Earlier time to diagnosis after hematopoietic cell transplant and severity of FVC
at diagnosis were significantly associated with reduced survival. CONCLUSIONS:
The FEV1 trajectory in patients with BOS after hematopoietic cell transplant in a
contemporary era of management follows a predominant pattern of rapid FEV1
decline in the 6 months prior to diagnosis, followed by FEV1 stabilization after
diagnosis.
PMID- 27513371
TI - Nanometer-sized emissions from municipal waste incinerators: A qualitative risk
assessment.
AB - Municipal waste incinerators (MWI) are beneficial alternatives to landfills for
waste management. A recent constituent of concern in emissions from these
facilities is incidental nanometer-sized particles (INPMWI), i.e., particles
smaller than 1 micrometer in size that may deposit in the deepest parts of the
lungs, cross into the bloodstream, and affect different regions of the body. With
limited data, the public may fear INPMWI due to uncertainty, which may affect
public acceptance, regulatory permitting, and the increased lowering of air
quality standards. Despite limited data, a qualitative risk assessment paradigm
can be applied to determine the relative risk due to INPMWI emissions. This
review compiles existing data on nanometer-sized particle generation by MWIs,
emissions control technologies used at MWIs, emission releases into the
atmosphere, human population exposure, and adverse health effects of nanometer
sized particles to generate a qualitative risk assessment and identify data gaps.
The qualitative risk assessment conservatively concludes that INPMWI pose a low
to moderate risk to individuals, primarily due to the lack of relevant
toxicological data on INPMWI mixtures in ambient particulate matter.
PMID- 27513372
TI - Understanding the sorption mechanisms of aflatoxin B1 to kaolinite, illite, and
smectite clays via a comparative computational study.
AB - In current adsorption studies of biotoxins to phyllosilicate clays, multiply weak
bonding types regarding these adsorptions are not well known; the major
attractive forces, especially for kaolinite and illite, are difficult to be
identified as compared to smectite with exchangeable cations. Here, we
discriminated the bonding types of aflatoxin B1 (AFB1) contaminant to these clays
by combined batch experiment with model computation, expounded their bonding
mechanisms which have been not quantitatively described by researchers. The
observed adsorbent-to-solution distribution coefficients (Kd) of AFB1 presented
in increasing order of 18.5-37.1, 141.6-158.3, and 354.6-484.7L/kg for kaolinite,
illite, and smectite, respectively. Normalization of adsorbent-specific surface
areas showed that adsorption affinity of AFB1 is mainly dependent on the outside
surfaces of clay aggregates. The model computation and test of ionic effect
further suggested that weakly electrostatic attractions ((Si/Al-OH)2?(OC)2) are
responsible for AFB1-kaolinite adsorption (Kd, 18.5-37.1L/kg); a moderate
electron-donor-acceptor attraction ((CO)2?K+?(O-Al)3) is related to AFB1-illite
adsorption (Kd, 141.6-158.3L/kg); a strong calcium-bridging linkage
((CO)2?Ca2+?(O-Si)4) is involved in AFB1-smectite adsorption (Kd, 354.6
484.7L/kg). Changes in Gibbs free energy (DeltaG degrees ) suggested that the
computed result is reliable, providing a good reproduction of AFB1-clay
interaction.
PMID- 27513373
TI - Chlortetracycline removal by using hydrogen based membrane biofilm reactor.
AB - In the last years, increasing attention has been paid on the presence of
antibiotics in aqueous environments due to their ecological damage and potential
adverse effects on organisms. Membrane biofilm reactors (MBfR) have been gained a
significant popularity as an advanced wastewater treatment technology in removing
of organic micro-pollutants. In this study, the performance of H2-MBfR for
simultaneous removal of nitrate and chlortetracycline, formation of
transformation products and community analysis of the biofilm grown on the gas
permeable hollow fiber membranes was evaluated by considering effect of the
hydraulic retention time, surface loadings of target pollutants and H2 pressure.
The results showed that the simultaneous chlortetracycline (96%) and nitrate
removal (99%) took placed successfully under the conditions of 5h HRT and 2psi H2
pressure. It has been determined that the main elimination process was
biodegradation and Betaproteobacteria species was responsible for
chlortetracycline degradation.
PMID- 27513375
TI - Low dose verapamil as an adjunct therapy for medically refractory epilepsy - An
open label pilot study.
AB - Previous studies using verapamil as an adjunct therapy to anti-seizure
medications have used doses ranging from 120 to 240mg per day. However, despite
showing promising results, there was an increased incidence of side effects. The
aim of this study is to assess the efficacy and tolerability of low dose
verapamil (20mg p.o. tid) as adjunct therapy to patient's anti-seizure
medications irrespective of the type or etiology of the epilepsy. In an open
label pilot study we enrolled 20 adult patients with history of epilepsy who
continued to have a minimum of 2 seizures a month despite being on or having
tried maximum tolerated doses of 3 or more standard antiepileptic drugs under the
supervision of an epileptologist. 10 of the 19 patients (53%) who continued in
the study had >50% reduction in seizure frequency. 2 of the patients (10%) had
<50% seizure reduction. The remaining 7 patients (37%) had no reduction in their
seizures. There was no discontinuation due to adverse events. P-Glycoprotein is a
prototypical drug transporter that has been strongly implicated in drug
resistance in epilepsy. Verapamil at a relatively low dose was well tolerated
compared to previous studies which used up to 240mg per day and seems to have
contributed to a statistically significant improvement in seizure control in
patients with medically refractory epilepsy, especially in patients with Lennox
Gastaut syndrome. A randomized double blind controlled study at this low dose
with larger sample size may be more informative.
PMID- 27513374
TI - Compromised GABAergic inhibition contributes to tumor-associated epilepsy.
AB - Glioblastoma Multiforme (GBM) is the most common form of primary brain tumor with
30-50% of patients presenting with epilepsy. These tumor-associated seizures are
often resistant to traditional antiepileptic drug treatment and persist after
tumor resection. This suggests that changes in the peritumoral tissue underpin
epileptogenesis. It is known that glioma cells extrude pathological
concentrations of glutamate which is thought to play a role in tumor progression
and the development of epilepsy. Given that pathological concentrations of
glutamate have been shown to dephosphorylate and downregulate the potassium
chloride cotransporter KCC2, we hypothesized that glioma-induced alterations in
KCC2 in the peritumoral region may play a role in tumor-associated epilepsy.
Consistent with this hypothesis, we observe a decrease in total KCC2 expression
and a dephosphorylation of KCC2 at residue Ser940 in a glioma model which
exhibits hyperexcitability and the development of spontaneous seizures. To
determine whether the reduction of KCC2 could potentially contribute to tumor
associated epilepsy, we generated mice with a focal knockdown of KCC2 by
injecting AAV2-Cre-GFP into the cortex of floxed KCC2 mice. The AAV2-Cre-mediated
knockdown of KCC2 was sufficient to induce the development of spontaneous
seizures. Further, blocking NKCC1 with bumetanide to offset the loss of KCC2
reduced the seizure susceptibility in glioma-implanted mice. These findings
support a mechanism of tumor-associated epilepsy involving downregulation of KCC2
in the peritumoral region leading to compromised GABAergic inhibition and suggest
that modulating chloride homeostasis may be useful for seizure control.
PMID- 27513376
TI - An Improved Surgical Technique for Pure Laparoscopic Left Hemihepatectomy: Ten
Years Experience in a Tertiary Center.
AB - BACKGROUND: This study details our experience with an improved surgical technique
involving the hepatic pedicle during laparoscopic left hemihepatectomy (LLH).
METHODS: We describe an improved laparoscopic technique to extraparenchymally
divide the left hepatic pedicle. A retrospective analysis of all of the patients
who underwent laparoscopic liver procedures between 2002 and 2012 was conducted.
The patients were divided into two groups, an early LLH group (ELLH group) and a
recent LLH group (RLLH group), based on the surgical approach used for the left
hepatic pedicle. RESULTS: A total of 72 cases of LLH (26 ELLH and 46 RLLH) were
identified. The RLLH group exhibited a shorter median operative time, median
length of hospital stay, and lower median blood loss compared to the ELLH group
(182, 162.5-223.7 versus 232.5, 200-357.5 minutes, P < .01; 5, 4.2-7 versus 7, 6
8.7 days, P < .05; 150, 100-257.5 versus 300, 200-337.5 mL, P < .05,
respectively). No perioperative mortality was observed. CONCLUSIONS: This study
confirms that our improved surgical technique for LLH is practical, safe, and
effective. The main advantage of this method compared to other techniques is the
possibility of attaining rapid and precise control of vascular inflow, thus
facilitating LLH.
PMID- 27513377
TI - A Daily Diary Analysis of Condom Breakage and Slippage During Vaginal Sex or Anal
Sex Among Adolescent Women.
AB - BACKGROUND: Adolescent women are disproportionately impacted by the adverse
outcomes associated with sexual activity, including sexually transmitted
infections (STI). Condoms as a means of prevention relies on use that is free of
usage failure, including breakage and/or slippage. This study examined the daily
prevalence of and predictors of condom breakage and/or slippage during vaginal
sex and during anal sex among adolescent women. METHODS: Adolescent women (N =
387; 14 to 17 years) were recruited from primary care clinics for a longitudinal
cohort study of STIs and sexual behavior. Data were daily partner-specific sexual
diaries. Random intercept mixed-effects logistic regression was used to estimate
the fixed effect of each predictor on condom breakage/slippage during vaginal or
during anal sex (Stata, 13.0), adjusting model coefficients for the correlation
between repeated within-participant diary entries. RESULTS: Condom slippage
and/or breakage varied across sexual behaviors and was associated with individual
specific (eg, age and sexual interest) and partner-specific factors (eg,
negativity). Recent behavioral factors (eg, experiencing slippage and/or breakage
in the past week) were the strongest predictors of current condom slippage and/or
breakage during vaginal or anal sex. CONCLUSIONS: Factors associated with young
women's condom breakage/slippage during vaginal or during anal sex should be
integrated as part of STI prevention efforts and should be assessed as part of
ongoing routine clinical care.
PMID- 27513378
TI - Increased Partner Risk Characteristic Among Adolescents Using Alcohol In the
Moment.
AB - BACKGROUND: Alcohol is a recognized risk factor for sexually transmitted diseases
acquisition, but the mechanism is unclear. Potentially, adolescents using alcohol
in the 2 hours before sex (in-the-moment use) have riskier sexual partners.
METHODS: We used multivariable logistic regression to examine the association
between in-the-moment alcohol use and partner risk characteristics reported for
the most recent sex among primarily 17- to 18-year-old adolescents originally
recruited from a representative sample of Chicago public elementary schools. We
created 3 composite partner risk profiles: partner familiarity risk (casual and
unexpected), partner context risk (age discordance and met in public), and
overall risk using all measures except partner alcohol use. RESULTS: Teens who
reported any in-the-moment alcohol use were more likely than nondrinking teens to
report casual (adjusted odds ratio [AOR], 3.2; 95% confidence interval [95% CI],
2.1-4.9), unexpected (AOR, 1.6; 95% CI, 1.0-2.5), age discordant (AOR, 3.0; 95%
CI, 2.0-4.6), or met in public partners (AOR, 1.4; 95% CI, 1.0 to 2.1). For each
composite measure, the number of partner risk characteristics reported increased
linearly with the percent of teens drinking in the moment (Cochran-Armitage
trend, P < 0.0001). Compared with zero characteristics, in-the-moment alcohol use
was associated with increased odds of reporting 1 (AOR, 2.8; 95% CI, 1.7-4.5), 2
(AOR, 4.6; 95% CI, 2.7, 7.6), or 3 to 4 characteristics (AOR, 7.1; 95% CI, 3.3
15.3). CONCLUSIONS: Our findings expand the link between in-the-moment alcohol
use and partner risk reported in prior studies to encompass adolescents' general
sexual experiences and additional partner characteristics including the highly
associated composite characteristics.
PMID- 27513379
TI - Cost-Effectiveness of Dual Antimicrobial Therapy for Gonococcal Infections Among
Men Who Have Sex With Men in the Netherlands.
AB - BACKGROUND: In response to the rising threat of resistance to first-line
antibiotics for gonorrhea, international guidelines recommend dual antimicrobial
therapy. However, some countries continue to recommend monotherapy. We assess the
cost-effectiveness of dual therapy with ceftriaxone and azithromycin compared
with monotherapy with ceftriaxone, for control of gonorrhea among men who have
sex with men in the Netherlands. METHODS: We developed a transmission model and
calculated the numbers of new gonorrhea infections, consultations at health care
specialists, tests, and antibiotic doses. With these numbers, we calculated costs
and quality-adjusted life-years (QALY) with each treatment; and the incremental
cost-effectiveness ratio (ICER) of dual therapy compared to monotherapy. The
impact of gonorrhea on human immunodeficiency virus transmission was not included
in the model. RESULTS: In the absence of initial resistance, dual therapy can
delay the spread of ceftriaxone resistance by at least 15 years, compared to
monotherapy. In the beginning, when there is no resistance, dual therapy results
in high additional costs, without any QALY gains. When resistance spreads over
time, the additional costs of dual therapy decline, the gained QALYs increase,
the ICER drops off and, after 50 years, falls below &OV0556;20,000 per QALY
gained. If azithromycin resistance is initially prevalent, resistance to the
first-line treatment rises almost equally fast with both treatment strategies and
the ICER remains extremely high. CONCLUSIONS: Compared with ceftriaxone
monotherapy, dual therapy with ceftriaxone and azithromycin can considerably
delay the spread of ceftriaxone resistance, but may only be cost-effective in the
long run and in the absence of initial resistance.
PMID- 27513380
TI - Deja vu? A Comparison of Syphilis Outbreaks in Houston, Texas.
AB - BACKGROUND: After reaching an all-time low in 2000, syphilis incidence in the
United States has increased as the burden shifted from heterosexuals to men who
have sex with men (MSM). Houston, Texas, experienced 2 outbreaks of syphilis
during this transformation in trends. Further evaluation is necessary to
determine if these outbreaks occurred among the same subpopulations. METHODS:
Surveillance data collected on all reported infectious syphilis cases in Houston
from 1971 to 2013 were analyzed. Trends in incidence among MSM and human
immunodeficiency virus-positive Houston residents were examined. Peak syphilis
years subsequent to 1999, years 2007 and 2012, were compared to determine if
outbreaks arose in distinctive subpopulations. Categorical variables between
these years were compared using chi-square and Fisher's exact tests, whereas
further associations between the years were evaluated using multivariable
logistic regression. RESULTS: Incidence among MSM was 20.9 to 32.1 times higher
than other men from 2005 to 2013. After adjusting for covariates, cases in 2012
were significantly more likely to be Hispanic (adjusted odds ratio [AOR] = 1.61;
95% confidence interval [95% CI], 1.03-2.53), reported meeting partners via the
Internet (AOR, 1.74; 95% CI, 1.18-2.58), and engaged in anonymous sex (AOR, 1.92;
95% CI, 1.40-2.63) in comparison to cases in 2007. CONCLUSIONS: We found marked
disparities of syphilis by subpopulation in Houston. Herein, we present evidence
that outbreaks have been distinct in a major southern city with a high burden of
syphilis.
PMID- 27513381
TI - Full House: A Retrospective Analysis of High Sexually Transmitted Infection
Prevalence among Adult Film Actors at a Singular Residence.
AB - BACKGROUND: During a routine human immunodeficiency virus (HIV) investigation,
Florida Department of Health staff identified a house (house A) in which over 150
individuals had resided at least briefly. Further investigation revealed that
house A is used by the producer of a small adult film production company to board
his actors. This report describes sexually transmitted infection (STI) prevalence
among male actors in gay adult films residing in a common Florida residence.
METHODS: LexisNexis Accurint was used to identify house A residents since October
2002 when the producer arrived. Information on STIs and interview data were
obtained from Florida's STI surveillance system. An infection was considered to
be associated with residence in house A if the date of diagnosis occurred 6
months before an individual's residence start date through 6 months after his
residence end date. RESULTS: Excluding the producer, 150 men resided in house A
starting from September 2003 to July 2015. Forty-six individuals had a reported
case of HIV, syphilis, gonorrhea, and/or chlamydia with 92 infections total.
Forty-two (46%) infections among 24 men were considered associated with residence
in house A. CONCLUSIONS: LexisNexis Accurint was a useful tool for identifying
house A residents, a highly mobile and highly sexually active population. There
is a high prevalence of STIs among residents, but it is unclear where
transmission is occurring. Settings like house A are good candidates for HIV pre
exposure prophylaxis and active STI screenings and may be an opportunity for
public health officials to intervene in high-risk groups to reduce STI rates in
the community.
PMID- 27513382
TI - Earlier Detection of Hepatitis C Virus Infection Through Routine Hepatitis C
Virus Antibody Screening of Human Immunodeficiency Virus-Positive Men Who Have
Sex With Men Attending A Sexually Transmitted Infection Outpatient Clinic: A
Longitudinal Study.
AB - BACKGROUND: In 2007, routine hepatitis C virus (HCV) antibody testing was
introduced for men who have sex with men (MSM) with a human immunodeficiency
virus (HIV)-positive or unknown status attending a Dutch sexually transmitted
infection (STI) outpatient clinic. We evaluated whether this screening resulted
in additional and earlier HCV diagnoses among MSM who also attend HIV clinics.
METHODS: At first STI consultation, HIV-positive MSM and MSM opting-out of HIV
testing (HIV-status-unknown) were tested for HCV antibodies (anti-HCV). During
follow-up consultations, only previously HCV-negative men were tested.
Retrospectively, STI clinic and HIV clinic HCV diagnosis dates were compared.
RESULTS: One hundred twelve (6.4%) of 1742 (95% confidence interval [CI], 5.3
7.6%) HIV-positive and 3 (0.7%) of 446 (95% CI, 0.2-2.0%) HIV-status-unknown MSM
tested anti-HCV-positive at first consultation. During follow-up consultations,
32 HIV-positive (incidence HCV-positive: 2.35/100 person years (PY) (95% CI, 1.66
3.33)) and 0 (1-sided, 97.5% CI, 0.0-3.76) HIV-status-unknown MSM became anti-HCV
positive. Four (11.8%) of 34 HIV-positive MSM notified by their sexual partner of
HCV tested anti-HCV-positive.Of 163 HIV-positive MSM with HCV antibodies, 78
reported a history of HCV. HCV diagnosis data at the HIV clinic was requested for
the remaining 85 MSM and available for 54 MSM. Of these 54 MSM, 28 (51.9%) had
their first HCV diagnosis at the STI clinic, of whom 7 concurrently with HIV. At
their next scheduled HIV clinic consultation, 3 HCV cases probably would have
been missed. CONCLUSIONS: The introduction of routine anti-HCV testing at the STI
outpatient clinic resulted in additional and earlier HCV detection among HIV
positive MSM. Testing should be continued among HIV-positive MSM, at least for
those not (yet) under the care of an HIV clinic and those notified of HCV by
their sexual partner.
PMID- 27513383
TI - Attitudes and Willingness to Assume Risk of Experimental Therapy to Eradicate
Genital Herpes Simplex Virus Infection.
AB - BACKGROUND: Current treatment of genital herpes is focused on ameliorating signs
and symptoms but is not curative. However, as potential herpes simplex virus
(HSV) cure approaches are tested in the laboratory, we aimed to assess the
interest in such studies by persons with genital herpes and the willingness to
assume risks associated with experimental therapy. METHODS: We constructed an
anonymous online questionnaire that was posted on websites that provide
information regarding genital herpes. The questions collected demographic and
clinical information on adults who self-reported as having genital herpes, and
assessed attitudes toward and willingness to participate in HSV cure clinical
research. RESULTS: Seven hundred eleven participants provided sufficient
responses to be included in the analysis. Sixty-six percent were women; the
median age was 37 years, and the median time since genital HSV diagnosis was 4.7
years. The willingness to participate in trials increased from 59.0% in phase 1
to 68.5% in phase 2, and 81.2% in phase 3 trials, and 40% reported willingness to
participate even in the absence of immediate, personal benefits. The most
desirable outcome was the elimination of risk for transmission to sex partner or
neonate. The mean perceived severity of receiving a diagnosis of genital HSV-2
was 4.2 on a scale of 1 to 5. CONCLUSIONS: Despite suppressive therapy available,
persons with genital herpes are interested in participating in clinical research
aimed at curing HSV, especially in more advanced stages of development.
PMID- 27513384
TI - Higher HPV16 and HPV18 Penile Viral Loads Are Associated With Decreased Human
Papillomavirus Clearance in Uncircumcised Kenyan Men.
AB - BACKGROUND: Whether higher penile human papillomavirus (HPV) viral load is
associated with a lower rate of HPV clearance remains unknown. OBJECTIVES: We
examined the association between penile HPV16 and HPV18 viral load and subsequent
HPV clearance in uncircumcised Kenyan men. STUDY DESIGN: Participants were human
immunodeficiency virus (HIV)-seronegative, sexually active, 18- to 24-year-old
men randomized to the control arm of a male circumcision trial in Kisumu, Kenya.
Men provided exfoliated penile cells from two anatomical sites (glans/coronal
sulcus and shaft) every 6 months for 2 years. GP5+/6+ polymerase chain reaction
was used to identify 44 HPV-DNA types. Human papillomavirus viral load testing
was conducted using a LightCyler real-time polymerase chain reaction assay; viral
load was classified as high (>250 copies/scrape) or low (<=250 copies/scrape),
for nonquantifiable values. The Kaplan-Meier method and Cox regression modeling
were used to examine the association between HPV viral load and HPV clearance.
RESULTS: A total of 1097 men, with 291 HPV16 and 131 HPV18 cumulative infections
over 24 months were analyzed. Human papillomavirus clearance at 6 months after
first HPV detection was lower for high versus low viral load HPV16 infections in
the glans (adjusted hazard ratio [aHR], 0.65; 95% confidence interval [CI], 0.46
0.92)] and shaft (aHR, 0.44; 95% CI, 0.16-0.90), and HPV18 infections in the
glans (aHR, 0.05; 95% CI, 0.01-0.17). DISCUSSION: High versus low HPV viral load
was associated with a reduced HPV clearance for HPV16 infections in the glans and
shaft, and for HPV18 infections in the glans, among young uncircumcised men.
Reduced clearance of high viral load HPV16 and HPV18 infections in men may
increase HPV transmission to their female partners as well as enhance the
development of penile lesions in comparison to men with low viral load HPV
infections.
PMID- 27513386
TI - A Case of Reactive Arthritis Associated With Lymphogranuloma Venereum Infection
in a Woman.
AB - We report the first case of reactive arthritis associated with lymphogranuloma
venereum (LGV) in an Italian human immunodeficiency virus-negative woman with
urogenital and rectal Chlamydia trachomatis L2 serovar infection. The LGV
associated arthritis has to be considered even when classic symptoms of arthritis
are missing and in case of asymptomatic or cryptic LGV localizations.
PMID- 27513385
TI - Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in
Recently Isolated Clinical Strains.
AB - BACKGROUND: High rates of 23S rDNA mutations implicated in macrolide resistance
have been identified in Treponema pallidum samples from syphilis patients in many
countries. Nonetheless, some clinicians have been reluctant to abandon
azithromycin as a treatment for syphilis, citing the lack of a causal association
between these mutations and clinical evidence of drug resistance. Although
azithromycin resistance has been demonstrated in vivo for the historical Street
14 strain, no recent T. pallidum isolates have been tested. We used the well
established rabbit model of syphilis to determine the in vivo efficacy of
azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from
patients with syphilis in Seattle, Wash. METHODS: Groups of 9 rabbits were each
infected with a strain containing 23S rDNA mutation A2058G (strains UW074B,
UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild
type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3
animals per strain were treated with azithromycin, 3 were treated with benzathine
penicillin G, and 3 served as untreated control groups. Treatment efficacy was
documented by darkfield microscopic evidence of T. pallidum, serological
response, and rabbit infectivity test. RESULTS: Azithromycin uniformly failed to
cure rabbits infected with strains harboring either 23S rDNA mutation, although
benzathine penicillin G was effective. Infections caused by wild type strains
were successfully treated by either azithromycin or benzathine penicillin G.
CONCLUSIONS: A macrolide resistant phenotype was demonstrated for all strains
harboring a 23S rDNA mutation, demonstrating that either A2058G or A2059G
mutation confers in vivo drug resistance.
PMID- 27513387
TI - Human Immunodeficiency Virus Testing Practices and Interest in Self-Testing
Options Among Young, Black Men Who Have Sex With Men in North Carolina.
AB - BACKGROUND: Young, black men who have sex with men (YBMSM) experience
disproportionately high human immunodeficiency virus (HIV) incidence in the
United States. Relative to other at-risk populations, less is known about their
HIV testing behaviors and preferences regarding self-testing. METHODS: We used an
online survey to investigate testing practices and interest in self-testing among
HIV-uninfected, 18- to 30-year-old YBMSM in North Carolina. RESULTS: From July
2014 to March 2015, 212 completed the survey; median age was 24 years. Among 175
(83%) who had ever been tested, 160 (91%) reported testing in the prior year, 124
(71%) tested at least every 6 months, and 71 (40%) tested at least quarterly.
About three quarters (77%; n = 164) were aware of HIV self-testing; 35 (17%) had
ever purchased rapid (n = 27) or dried blood spot-based (n = 14) kits.
Participants aware of kits had greater intention to test in the next 6 months,
were more likely to have income for basic necessities and to ask sex partners
about HIV status, and were less likely to have a main sex partner or to have had
transactional sex. Among 142 participants at least somewhat likely to self-test
in the future, convenience (35%), privacy (23%), and rapid result delivery (18%)
were the principal motivators. CONCLUSIONS: Eight of every 10 YBMSM have ever
been tested for HIV, but intertest intervals remain unacceptably long for many.
Awareness of and interest in self-testing is substantial, but few have used this
method. Expanded use of self-tests could help increase the frequency of HIV
testing in this epidemiologically important population.
PMID- 27513388
TI - Emergency department visits caused by adverse drug reactions: results of aTurkish
university hospital.
AB - BACKGROUND/AIM: We aimed to evaluate adverse drug reaction (ADR)-related
emergency department (ED) visits in the ED of the Dokuz Eylul University Hospital
prospectively. MATERIALS AND METHODS: Patients who were admitted to the ED during
1-week periods of four different seasons between July 2010 and April 2011 were
enrolled. Demographics of patients, previous ADR history, clinical progress, and
outcomes were recorded. Causality assessment was done according to World Health
Organization Uppsala Monitoring Centre categories. ADRs were categorized as
certain, probable, or possible. RESULTS: Patients who were on medications (26.5%,
n = 1838) were evaluated for ADR-related ED admissions. ADRs accounted for 5.9%
of cases (n = 108). The most frequently affected systems were the
gastrointestinal (35.2%, n = 38), dermatological (23.1%, n = 25), and
hematological (10.2%, n = 11) systems (7.4%, n = 8). The most common causes of
ADRs were antiinfectives (31.6%, n = 33). Amoxicillin, Coumadin, and paracetamol
were the most common medications that caused ADRs. CONCLUSION: Nearly 6% of the
admissions were ADR-related. ADRs should always be considered when patients who
are on medication are admitted to the ED. Multicenter epidemiologic studies are
required to know the real rates of ADR cases in EDs in Turkey.
PMID- 27513389
TI - Evaluation of brainstem auditory evoked potentials and their relationshipwith
levels of thyroid autoantibodies in patients with vitiligo.
AB - BACKGROUND/AIM: Vitiligo is a common depigmenting disorder. The damage can also
occur in similar ways to melanocytes within other organs. We evaluated the
brainstem and auditory pathway functions by evaluating brainstem auditory evoked
potentials (BAEPs) and whether there is any relationship between auditory
functions and autoimmunity. MATERIALS AND METHODS: Forty patients with vitiligo
and 20 healthy volunteers were enrolled. Thyroid functions and autoantibodies
were examined and BAEP tests were assessed by a neurologist. RESULTS: Antithyroid
peroxidase (anti-TPO) and antithyroglobulin (anti-TGA) antibody positivity was
higher in the patient group (P < 0.05). A negative correlation was detected
between anti-TPO and lead III, IV, and V latency and I-III interpeak latency
(IPL) of the right ear together with lead IV latency and I-V IPL of the left ear
in the patient group. When each BAEP parameter was compared between the two
groups, more abnormalities were detected in the V latency and III-V IPL of the
left ear together with IV and V latency of the right ear. CONCLUSION: In this
study the presence of a correlation between increased anti-TGA and anti-TPO
levels and BAEP parameters may be related to an autoimmune-mediated mechanism.
However, further studies are needed to be performed in a large patient series.
PMID- 27513390
TI - Health-related behaviors and nutritional status of adolescents who study
asboarders and day-students.
AB - BACKGROUND/AIM: Boarders and day-students study together in regional boarding
schools. This study was carried out to compare the health and nutritional status
of boarders and day-students who study at regional boarding schools in Turkey.
MATERIALS AND METHODS: A total 634 boarders and 492 day-students in the 4th-8th
years of nine boarding schools in Giresun Province of Turkey were included. A
questionnaire including 49 questions about sociodemographic characteristics and
health and nutritional status was completed by the students. Height and weight
measurements of the students were also taken. The chi-square test was used for
statistical analyses. RESULTS: The boarders evaluated their health status as
worse than the day-students. The proportion of the students having three meals a
day was higher among the boarders than the day-students. According to BMI values,
11% of the boarders were evaluated as underweight, 77% as normal, 9.5% as
overweight, and 2.5% as obese. These proportions were respectively 15.5%, 67.3%,
12.8%. and 4.5% for the day-students. CONCLUSION: The boarders have more regular
diets and the proportion of normal-weighed boarders was higher than that of the
day-students. However, they perceived their health as worse than the day-tudents.
PMID- 27513391
TI - MEFV mutations in Iranian Azari Turkish patients with Henoch-Schonlein purpura.
AB - BACKGROUND/AIM: The aim of the current study was to screen the rate of MEFV
mutations in Henoch-Schonlein purpura (HSP) and to investigate the association of
these mutations plus clinical symptoms with HSP disease in the Iranian Azari
Turkish ethnic group. MATERIALS AND METHODS: The study groups included 40
unrelated HSP patients and 200 apparently healthy people without any kind of
inflammatory diseases as a control group. Molecular screening was performed for
eight main mutations, namely M694V, M694I, M680I, V726A, E148Q, R761H, P396S, and
R408Q, using polymerase chain reaction (PCR), restriction fragment length
polymorphism (RFLP), and sequencing. RESULTS: Out of the 40 studied patients, 27
subjects (67.5%) did not show any mutation, whereas 10 patients (25%) were
heterozygotes for one of the following mutations: M694V, M680I, V726A, E148Q.
Moreover, three patients (7.5%) were compound heterozygotes for P369S and R408Q.
The significant differences between the patient and control groups for M680I,
V726A, E148Q, P396S, and R408Q were P = 0.0043, P = 0.0324, P = 0.0145, P =
0.0043, and P = 0.0043, respectively. Furthermore, no significant difference in
clinical manifestations was observed between the two groups of patients with and
without mutations. CONCLUSION: Based on the results, MEFV mutations could be
considered effective genetic factors for development of HSP in the Iranian Azari
Turkish ethnic group.
PMID- 27513392
TI - Causes of open fractures: orthopaedic injuries related to home-made agricultural
vehicles in the eastern Black Sea region of Turkey.
AB - BACKGROUND/AIM: Small vehicles known locally as pat-pats, which are used in
agricultural work, are forbidden in traffic. The inherent instability of the
vehicle may result in accidents, both on farmland and in traffic. The aim of this
study was to evaluate orthopaedic injuries related to pat-pats. MATERIALS AND
METHODS: Patients hospitalised for pat-pat accidents in two central hospitals in
Samsun between December 2006 and October 2013 were scanned using ICD codes. A
total of 46 patients with orthopaedic injuries (43 male, 3 female) with a mean
age of 36 +/- 13.3 years were evaluated. RESULTS: The most injured age group was
between 10 and 49 years (n = 40, 87%), and accidents occurred most in summer (n =
30, 65%). Open fractures were determined in 42 (91%) patients. Amputation was
necessary in 4 (8%) patients. The hospitalisation period was a mean of 17.1 +/-
14 days. A statistically significant relationship was determined between open
fracture type and the hospitalisation period (P < 0.001). CONCLUSION: As most of
the orthopaedic injuries related to home-made agricultural machines are open
fractures, it is important to guard against these types of injuries. The
regulations that these machines are not used in traffic should be enforced and
safer practices should be applied for use in agriculture.
PMID- 27513393
TI - Fluctuations of state anxiety, spinal structure, and postural stabilityacross the
menstrual cycle in active women.
AB - BACKGROUND/AIM: To investigate differences in state anxiety, spinal posture and
mobility, postural competency, and stability across the menstrual cycle in active
women. MATERIALS AND METHODS: Thirteen physically active women (18-25 years) with
a regular menstrual cycle were recruited. Anxiety with the Spielberger State
Trait Anxiety Inventory; spinal posture, mobility, and competency with a Spinal
Mouse device (Idiag, Fehraltorf, Switzerland); and postural stability with a
Biodex Balance System SD (Biodex Medical Systems, Inc., Shirley, NY, USA) were
evaluated across phases of the menstrual cycle. RESULTS: No significant
differences were observed between phases of the menstrual cycle for state
anxiety, spinal posture, mobility, or competency (P > 0.05). No differences were
found for static postural stability (P > 0.05); however, a significant difference
was detected in dynamic postural stability within three phases of the menstrual
cycle (P < 0.05). The highest values of overall stability, anterior-posterior and
mediolateral indexes were at menses; the lowest values were at the midluteal
phase. CONCLUSION: State anxiety, spinal posture, mobility, and postural
competence did not change across the menstrual cycle. However, dynamic stability
declined in menses. Improving awareness of dynamic stability impairment during
menses may be important toward injury prevention in active women.
PMID- 27513394
TI - The relationship between blood urea nitrogen levels and metabolic, biochemical,
and histopathologic findings of nondiabetic, nonhypertensive patients with
nonalcoholic fatty liver disease.
AB - BACKGROUND/AIM: Nonalcoholic fatty liver disease (NAFLD) is known as the most
common cause of chronic liver disease. It is accepted that the leading cause of
death in patients with NAFLD is from coronary events. Blood urea nitrogen (BUN)
was used as a prognostic indicator for cardiovascular disease. We aimed to
investigate the relationship between BUN levels and metabolic, biochemical, and
histopathologic findings of nondiabetic patients with NAFLD. MATERIALS AND
METHODS: A total of 195 male patients with biopsy proven NAFLD and 82 healthy
controls with normal liver and renal function tests and normal abdominal
ultrasonography were enrolled in the study. BUN levels were reviewed
retrospectively. RESULTS: The mean BUN levels of patients and controls were 13.07
(11.3-15.41) and 13.31 (10.97-15.87) mg/dL respectively. Patients were grouped as
simple steatosis (n = 33, 16.9%), borderline nonalcoholic steatohepatitis (n =
64, 32.8%), and nonalcoholic steatohepatitis (n = 98, 50.3%), and the BUN levels
of the histologic subgroups were 13.14 +/- 2.89, 14.34 +/- 3.04, and 13.71 +/-
3.21 mg/dL, respectively. We could not find any differences between the patient
group and control group with respect to BUN levels. CONCLUSION: Our findings
showed that there was no relationship between BUN levels and metabolic,
biochemical, and histopathologic findings of patients with NAFLD. Further
investigations, including in patients with late stages of NAFLD, are required.
PMID- 27513395
TI - An unusual pathology with an undefined etiology:solitary fibrous tumors of the
pleura.
AB - BACKGROUND/AIM: The aim of the present study was to evaluate the etiology and
clinical and pathological behavior of solitary fibrous tumors of the pleura
(SFTPs), as well as the most appropriate surgical approach and the results of
long-term follow-up of this condition. MATERIALS AND METHODS: Clinical and long
term follow-up records of 14 patients who had surgery for SFTP between 2001 and
2014 were reviewed retrospectively. Etiological factors, diagnostic procedures,
and clinical courses and outcomes for these patients were studied. RESULTS: Of
the 14 patients, 8 were male (57%) and 6 were female (43%) patients. The mean age
was 54.14 +/- 10.35 (41-75) years. There was no remarkable common etiological
factor. Preoperative diagnosis was achieved only in 2 patients. Predominant
symptoms were cough and chest pain. Complete resection was achieved in all
patients. Video-assisted thoracic surgery (VATS) was performed in 8 patients. All
but one patient were classified as having benign SFTP. The mean follow-up was
58.5 +/- 41.4 (10-132) months and no recurrence was noted in the follow-up.
CONCLUSION: These rarely seen tumors of the pleura are usually benign and
asymptomatic and their preoperative diagnosis is difficult. Clinical and
pathological behavior is still unpredictable and the treatment consists of
complete resection. Minimally invasive techniques such as VATS are recommended
for surgery if the tumor size is appropriate.
PMID- 27513396
TI - The effects of conscious sedation with nitrous oxide/oxygen on cognitive
functions.
AB - BACKGROUND/AIM: The aim of this study was to investigate the effects of conscious
sedation with 40% nitrous oxide/oxygen (N2O/O2) on cognitive functions. MATERIALS
AND METHODS: Forty dental patients referred to the sedation unit at Gazi
University Faculty of Dentistry Department of Oral and Maxillofacial Surgery
received a combination of 40% N2O/O2 inhalation for conscious sedation.
Psychometric tests were applied three times: before sedation, during sedation,
and at the end of the recovery, for assessing cognitive functions. RESULTS: The
results of this study showed that the 40% N2O/O2 combination impaired cognitive
functions during the conscious sedation. Recovery of most of the cognitive
functions occurred 15 min after sedation. However, in addition to the persistence
of 'hypnotic effects' and 'sensations of isolation' during the recovery period,
'motor loss value' showed more cognitive impairment 15 min after sedation than
before the sedation period, and, thus, the ability to execute fine motor skills
was not totally recovered by then. CONCLUSION: The results of this study could be
crucial for informing patients about avoiding attentive activities soon after
conscious sedation via 40% N2O/O2.
PMID- 27513397
TI - Comparison between the use of saline and seawater for nasal obstruction in
children under 2 years of age with acute upper respiratory infection.
AB - BACKGROUND/AIM: The effectiveness of isotonic and hypertonic saline solutions
used to open the nasal passage and improve clinical symptoms was compared in
children under 2 years of age admitted with the common cold. MATERIALS AND
METHODS: The study was performed as a randomized, prospective, and double-blind
study. The study included 109 children. The children using saline (0.9%) and
seawater (2.3%) as nasal drops (the patient group) and the control group (in
which nasal drops were not administered) were compared. Seventy-four patients
received nasal drops from package A (seawater) in single days and from package B
(physiological saline) in double days. RESULTS: The mean age of the patients was
9.0 +/- 3.9 months and the numbers of boys and girls were 65 (59.6%) and 44
(40.4%), respectively. There was no significant difference between Groups A and B
in terms of nasal congestion (P > 0.05). However, a significant difference was
found between the control group and Groups A and B (P < 0.05). CONCLUSION: Relief
was seen in nasal congestion, weakness, sleep quality, and nutrition with the use
of both saline and seawater in children with the common cold. Seawater or saline
drops may be added to standard treatment protocols.
PMID- 27513398
TI - Varicocele: tissue stress in the etiology.
AB - BACKGROUND/AIM: It is accepted that red blood cell distribution width (RDW) is a
novel prognostic marker that reflects oxidative stress and chronic inflammation.
In this study, we aimed to investigate the correlation between RDW and
varicocele, the etiology of which has not fully elucidated yet. This study also
aimed to study the mean platelet volume (MPV) values of the patient and control
group. MATERIALS AND METHODS: RDW and MPV levels were measured in 50 varicocele
subjects (group 1) and 48 healthy controls (group 2) from January 2012 to January
2014, retrospectively. RESULTS: MPV levels were significantly higher in group 1
than in group 2 (P < 0.001). Although the relationship was weak, the patients
with varicocele had significantly lower RDW values than did the controls (r: 0.24
P = 0.026). Positive correlations were not found between varicocele grade and MPV
and RDW values (P < 0.05). CONCLUSION: Higher MPV values are associated with
increased odds of developing varicocele.
PMID- 27513399
TI - Health promotion lifestyle profile scores are not associatedwith obesity in high
school students.
AB - BACKGROUND/AIM: Obesity is a cause of preventable morbidity and mortality with an
increasing prevalence. Health promoting lifestyle activities maintain or improve
an individual's health and in adolescence many habits are configured. The aim of
this study was to determine the prevalence of overweight and obesity among
adolescents and the relation between obesity and health promoting behaviors.
MATERIALS AND METHODS: This is a cross-sectional study including 848 high school
students aged 15-17. All students were administered a questionnaire including the
Health Promotion Life-Style Profile Scale. Weight and height were measured and
body mass index was calculated. Descriptive analysis, Pearson's chi-square test,
Kruskal-Wallis and Mann-Whitney U tests, and multivariate logistic regression
analysis were used. P < 0.05 was considered statistically significant. RESULTS:
Of the included students, 80.8% (n = 685) had normal ranges of body mass index,
10.1% (n = 86) were overweight, and 9.1% (n = 77) were obese. The Health
Promotion Life-Style Profile Scale average score was found to be 126.7 +/- 20.4.
There was no significant difference between Health Promotion Life-Style Profile
Scale and obesity (P = 0.921). CONCLUSION: Adolescence is an era of development
when individuals start to implement their own features to life. According to this
study adolescents do not perform health promoting lifestyles whether they are
obese or not.
PMID- 27513400
TI - Comparison of glomerular filtration rate measurements with the two-plasma sample
technique using Tc-99m DTPA and other methods in donor candidates for renal
transplantation.
AB - BACKGROUND/AIM: Accurate measurement of glomerular filtration rate (GFR) in the
evaluation of renal functions in potential kidney donors is associated with
important outcomes for both the donor and recipient. We intended to determine the
efficacy of various methods while estimating GFR in potential living kidney
donors. MATERIALS AND METHODS: Fifty-three potential kidney donors (31 females,
22 males; mean age: 50.1 years) were included in this study. GFR was estimated
simultaneously using the following methods: Gates' method, Cockcroft-Gault (CG)
and modification of diet in renal disease (MDRD) prediction equations, and the
two-plasma sample (TPS) technique. Using TPS as the reference method, the
estimations of GFR with the other methods were compared with that of TPS.
RESULTS: The mean +/- SD GFR was 86.43 +/- 11.37 mL min-1 1.73 m-2 with TPS. GFR
values calculated using Gates' method and MDRD 1, MDRD 2, reexpressed MDRD, and
CG prediction equations were 105.25 +/- 16.12 mL min-1 1.73 m-2, 114.63 +/- 32.51
mL min-1 1.73 m-2, 113.2 +/- 35.23 mL min-1 1.73 m-2, 104.23 +/- 23.12 mL min-1
1.73 m-2, and 99.35 +/- 20.01 mL min-1 1.73 m-2, respectively. While there was a
strong statistically significant correlation between the TPS and Gates' methods,
moderate correlation was found between TPS and the MDRD 1, MDRD 2, and
reexpressed MDRD prediction equations. CONCLUSION: Our results indicated that the
performance of Gates' method in total GFR estimation was better than the
prediction equations in potential kidney donors.
PMID- 27513401
TI - Plasma lipoprotein(a) levels are associated with the severity of coronaryheart
disease in Han Chinese people.
AB - BACKGROUND/AIM: The aim of this study was to investigate the association of
lipoprotein(a) [Lp(a)] with the severity of coronary heart disease (CHD) in Han
Chinese people. MATERIALS AND METHODS: Six hundred and seventy-nine patients with
angiographically defined CHD were enrolled in this cross-sectional study. Fasting
lipids were measured, and the severity of CHD was quantitatively assessed for
each patient according to the number of stenotic coronary branches and the
Gensini scoring system. RESULTS: The levels of Lp(a), total cholesterol (TC), low
density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol
(VLDL-C), and apolipoprotein (apo) B100 increased, while high-density lipoprotein
cholesterol (HDL-C) and apoAI decreased significantly with the number of stenotic
vessels. The levels of Lp(a) increased and HDL-C and apoAI decreased
significantly with the Gensini scores. The logistic regression analyses showed
that Lp(a) and HDL-C were independently associated with the number of stenotic
coronary vessels after adjusting for age, weight, body mass index, sex, smoking,
alcohol consumption, hypertension, diabetes, triglycerides, TC, LDL-C, VLDL-C,
apoAI, and apoB100. However, only Lp(a) was independently associated with the
Gensini scores after adjustment. CONCLUSION: Our data indicate that Lp(a) might
be a useful marker in predicting the severity of coronary heart disease.
PMID- 27513402
TI - Kinesiotaping as an alternative treatment method for carpal tunnel syndrome.
AB - BACKGROUND/AIM: Carpal tunnel syndrome (CTS) is the most common entrapment
neuropathy. Conservative treatment choices are not always satisfactory. The aim
of this study was to investigate the effect of kinesiotaping (KT) on pain level,
grip strength, and functional status compared with that of placebo KT and
orthotic device (OD) in patients with CTS. MATERIALS AND METHODS: In this
randomized, placebo-controlled study, participants were allocated into one of
three groups: an experimental KT group (Group 1), a placebo KT group (Group 2),
and an OD group (Group 3). Visual analogue scale (VAS) and Douleur Neuropathique
4 (DN4) scores, dynamometric grip strength measures, and the Boston CTS
questionnaire (BQ) were the outcome measures. RESULTS: All groups significantly
improved in terms of VAS scores (P < 0.05), DN4 scores (P < 0.05), and BQ scores
(P < 0.05). Grip strength improved in Group 3 (P = 0.001). There was a
significant difference among the groups with respect to BQ scores (P < 0.05).
CONCLUSION: KT application for the treatment of CTS should be an alternative
treatment choice.
PMID- 27513403
TI - The high prevalence of Encephalitozoon intestinalis in patients receiving
chemotherapy and children with growth retardation and the validity of real-time
PCR in its diagnosis.
AB - BACKGROUND/AIM: The aim of this study was to investigate the presence of
Encephalitozoon intestinalis in different patient groups consisting of
immunocompromised and immunocompetent individuals. MATERIALS AND METHODS: The
stool samples of 100 patients consisting of 25 patients receiving chemotherapy
and with acute gastrointestinal complaints, 25 with bone marrow transplant and
acute gastrointestinal complaints, 25 with urticaria, and 25 with growth
retardation were included in the study. As control groups, 25 subjects without
any chronic disease but with acute gastrointestinal complaints and 25 healthy
volunteers, making a total of 50 subjects, were included in the study. E.
intestinalis was investigated by IFA-MAbs and molecular methods. RESULTS: Forty
percent of patients receiving chemotherapy and with acute gastrointestinal
complaints, 24% of patients with bone marrow transplant and acute
gastrointestinal complaints, 20% of patients with urticaria, 40% of children with
growth retardation, and 28% of patients without any chronic disease but with
acute gastrointestinal complaints were determined as positive. CONCLUSION: To the
best of our knowledge, this is the first report to assess the relationship
between E. intestinalis and growth retardation. We think that the reliability of
the use of molecular methods, especially real-time PCR, should be improved for
the diagnosis of E. intestinalis.
PMID- 27513404
TI - Rectal or intramuscular diclofenac reduces the incidence of pancreatitis
afterendoscopic retrograde cholangiopancreatography.
AB - BACKGROUND/AIM: Acute pancreatitis is the most common adverse event of endoscopic
retrograde cholangiopancreatography (ERCP). We aimed to evaluate the efficacy of
intramuscular diclofenac sodium for prophylaxis of post-ERCP pancreatitis (PEP)
in comparison to the rectal form. MATERIALS AND METHODS: One hundred and fifty
consecutive patients who underwent ERCP were enrolled in this single-center,
prospective, randomized controlled study. Patients were randomized into three
groups. The first group received 75 mg of diclofenac sodium via intramuscular
route and the second group received 100 mg of diclofenac sodium rectally 30-90
min before the procedure. The third group served as the control group. Patients
were evaluated for post-ERCP pancreatitis with serum amylase levels and abdominal
pain 24 h after the procedure. RESULTS: The overall incidence of PEP was 6% (n =
9) and 2% (n = 1) in the intramuscular (IM) and rectal groups, respectively, and
14% in the control group (P = 0.014). Nineteen (12.7%) patients developed post
ERCP abdominal pain (8% in IM, 10% in rectal, and 20% in control group; P =
0.154). Twenty-five (16.6%) patients developed post-ERCP hyperamylasemia (10% in
IM, 12% in rectal, and 24% in control group; P = 0.03). CONCLUSION: Prophylaxis
with diclofenac given rectally or intramuscularly is an effective option for the
management of post-ERCP pancreatitis.
PMID- 27513405
TI - Macrolide and lincosamide resistance in staphylococcal clinical isolates in
Nablus, Palestine.
AB - BACKGROUND/AIM: Macrolide and lincosamide antibiotics are used for the treatment
of staphylococcal infections, especially for penicillin-allergic patients. In the
present study, we evaluate the prevalence of resistance to macrolide and
lincosamide antibiotics among staphylococci isolates. MATERIALS AND METHODS: A
total of 200 staphylococcal clinical isolates were collected from January 2012 to
April 2013. Minimal inhibitory concentrations of erythromycin and clindamycin
were determined by agar dilution method. An erythromycin-clindamycin induction
test was performed for isolates that were only resistant to erythromycin.
Representative erythromycin-resistant isolates were examined for erythromycin
resistance genes using PCR. RESULTS: Among staphylococci isolates, resistance
frequencies of erythromycin and clindamycin were 65.5% and 20.5%, respectively.
Erythromycin resistance was found to be mediated by putative efflux (50.4%) and
target site modification (49.6%). Inducible target site modification resistance
was detected in 19.1% of erythromycin-resistant isolates. Among the examined 36
staphylococci isolates, msr(A), erm(C), erm(A), and mef(A/E) genes were detected
in 55.6%, 30.6%, 25%, and 0%, respectively. CONCLUSION: Results of the current
study indicate the presence of high rates of macrolide resistance and inducible
phenotypes among staphylococcal isolates. It is also essential to keep in mind
variations of resistance rates among various age groups and specimen types.
PMID- 27513406
TI - Comparison of the effects of PEEP levels on respiratory mechanics and elimination
of volatile anesthetic agents in patients undergoing laparoscopic
cholecystectomy; a prospective, randomized, clinical trial.
AB - BACKGROUND/AIM: In laparoscopic procedures, intraabdominal carbon dioxide (CO2)
insufflation can cause decreased compliance, increased airway resistance, and
impaired ventilation-perfusion ratios. We aimed to investigate the effects of
intraoperative positive end-expiratory pressure (PEEP) treatment on respiratory
dynamics and elimination time of volatile anesthetic agents. MATERIALS AND
METHODS: In the present study, 75 ASA I-II patients were randomized into 3 groups
to receive 0 cmH2O PEEP (group I), 5 cmH2O PEEP (group II), or 8 cmH2O PEEP
(group III). Hemodynamic parameters, peak and plateau inspiratory airway
pressures (Ppeak, Pplateau), compliance values, the ratio of the fractions of
inspired and expired concentration of sevoflurane (Fi/Fexp sevoflurane) at 1 MAC,
times from 1 to 0.3 and 0.1 MAC and values for pulmonary function tests (PFT)
were recorded. RESULTS: Ppeak and Pplateau in group III were higher; compliance
values in group I and the extent of reduction in postoperative forced vital
capacity (FVC) in group III were lower than those in the other groups (P < 0.05).
No significant difference was observed between the groups regarding times from 1
to 0.3 MAC and times from 0.3 to 0.1 MAC. CONCLUSION: It was found that 8 cmH2O
PEEP increased compliance without clinically significant pulmonary deterioration
and that 8 cmH2O PEEP led to less impairment in postoperative PFTs compared to 0
and 5 cmH2O PEEP but had no effect on sevoflurane elimination time.
PMID- 27513407
TI - Effect of the application of prophylactic central compartment lymph node
dissectionon radioiodine ablation doses in patients with papillary thyroid
carcinoma.
AB - BACKGROUND/AIM: The aim of this study was to document the effect of the
application of prophylactic central compartment dissection on radioiodine
ablation activities for papillary thyroid carcinoma. MATERIALS AND METHODS: This
retrospective study included 452 (383 females, 69 males; mean age = 46.69 years,
min-max: 13-71) patients who received ablative radioiodine activity between April
2010 and December 2014. The histopathological reports of thyroidectomy and the
administered radioiodine activity were evaluated. Frequencies of prophylactic
central compartment dissection according to T stage of the primary tumor,
detection rate of lymph node metastases, and its effect on radioiodine ablation
activities were calculated. RESULTS: Prophylactic central compartment dissection
was applied for a total of 252 (56%) patients. The T stages of these patients
were T1a, T1b, T2, and T3 in 85 (34%), 106 (42%), 41 (16%), and 20 (8%) cases,
respectively. The administered radioiodine ablation activity was affected by
central compartment lymph node metastases in 112 (44%) patients. While 32 (29%)
of these patients had papillary microcarcinoma (T1a), 48 (43%), 20 (18%), and 12
(11%) of them had T1b, T2, and T3 tumors, respectively. CONCLUSION: The
application of prophylactic central compartment dissection affects the
radioiodine ablation activity in approximately half of patients. This effect is
more prominent in T1 stage tumors.
PMID- 27513408
TI - Effects of resveratrol on the alterations of cavernosal eNOS and LOX-1 expression
in the hypercholesterolemic condition: a preliminary study.
AB - BACKGROUND/AIM: The aim of this study was to determine the effects of resveratrol
on the alterations of cavernosal eNOS and LOX-1 mRNA expression in the
hypercholesterolemic condition. MATERIALS AND METHODS: Twenty-one New Zealand
white male rabbits were separated into three groups. Rabbits were fed with a
normal dietary intake for the control group and a 2% cholesterol diet for the
hypercholesterolemia and resveratrol groups for 6 weeks. Resveratrol 4 mg/kg
daily was administered for the resveratrol group. Cavernosal LOX-1 and eNOS mRNA
expressions were determined with real-time RT-PCR in all groups. The statistical
analysis was performed with the Kruskal-Wallis and Mann-Whitney U tests. RESULTS:
We found no difference between mean LOX-1 mRNA expression levels in the three
groups. Lower mean eNOS mRNA expression level was determined in the
hypercholesterolemia group when compared with the control group (P = 0.011). Mean
eNOS mRNA expression level in the resveratrol group was similar to that in the
control group but significantly higher than that in the hypercholesterolemia
group (P < 0.001). CONCLUSION: This preliminary study demonstrates the beneficial
effects of resveratrol on cavernosal eNOS expression. The presence of cavernosal
LOX-1 expression was also shown for the first time. Resveratrol may be an
alternative option in hypercholesterolemic erectile dysfunction with further
studies supporting its beneficial effects on the corpus cavernosum.
PMID- 27513409
TI - The efficacy of a through-the-scope sodium phosphate solution with completion
colonoscopy on the same day as a salvage option for inadequate bowel cleansing.
AB - BACKGROUND/AIM: The aim of this study was to investigate the efficacy of a
through- the-scope sodium phosphate solution with completion colonoscopy on the
same day as a salvage option for inadequate bowel preparation. MATERIALS AND
METHODS: All participants were instructed to eat a low residual diet for 3 days
before the scheduled colonoscopy and a clear liquid diet 18 h before the
colonoscopy. The patients were asked to take split doses of an oral sennoside
solution at 1800 and 2200 in the evening before the colonoscopy. In cases of
inadequate bowel preparation detected during routine colonoscopy, a sodium
phosphate solution was administered through the scope on the day of the
colonoscopy procedure. The degree of bowel cleansing was assessed by the Boston
Bowel Preparation Scale (BPS: 0-9). RESULTS: Almost excellent bowel cleansing was
obtained with a statistically significant difference between the degree of bowel
cleansing before and after the application of the sodium phosphate (Boston BPS:
5.48 +/- 1.01 vs. 8.88 +/- 0.33 respectively, P < 0.001). CONCLUSION: Through-the
scope sodium phosphate with completion colonoscopy on the same day was shown to
be an efficacious and acceptable method for inadequate bowel preparation.
PMID- 27513410
TI - Coexistence of preeclampsia and inherited thrombophilia in Turkish pregnant
women.
AB - BACKGROUND/AIM: To examine the relationship of inherited thrombophilia and other
thrombotic risk factors with preeclampsia (PE) in a population of pregnant
Turkish women. MATERIALS AND METHODS: This was a case cross-sectional study in
which 70 women with PE and 60 normal pregnant women were studied to find out the
frequency of women with risk factors including inherited thrombophilia among
preeclamptic cases. RESULTS: Hemoglobin, platelet count, uric acid, vitamin B12,
folic acid, copper, homocysteine, plasminogen activator inhibitor-1, fibrinogen,
protein S, protein C, activated protein C resistance values show significant
differences in women with PE in comparison to women with normal pregnancy.
CONCLUSION: There may be a link between inherited thrombophilia and PE, at least
in a sample of Turkish pregnant women. We also propose that the association
between thrombophilia and PE is stronger than suggested previously. Furthermore,
copper is selectively elevated in women with PE as an independent marker.
PMID- 27513411
TI - An analysis of the incidence of measles in Turkey since 1960.
AB - BACKGROUND/AIM: The aims of this study were to evaluate measles incidence and the
effect of elimination strategy interventions on the disease from 1960 to 2014 in
Turkey. The administration of measles vaccine started in the rural regions in
1970; it was carried out as a campaign along with the National Vaccine Campaign
in 1985, and it has been employed as combined measles, mumps, and rubella under
the scope of the Measles Elimination Program (MEP) since 2006 in Turkey. While a
dramatic decrease in the reporting of measles was observed between 2000 and 2010,
the number of the cases has increased since 2011. MATERIALS AND METHODS: The time
series of measles incidence was evaluated for possible structural changes with
regression models using dummy variables, autocorrelated with error terms.
RESULTS: The incidence of measles showed a statistically significant decline
between 1985 and 1988 (P = 0.0072) and between 2005 and 2011 (P < 0.0001).
However, a statistically significant increase in incidence was noted after 2013
(P = 0.0008). CONCLUSION: Over the last 54 years, the pattern of measles cases
demonstrated a significant decline in incidence. However, the increase in
incidence in 2013 should be carefully analyzed and interpreted in terms of the
MEP.
PMID- 27513412
TI - Reliability and validity of the Turkish version of myastheniagravis-quality of
life questionnaire-15 item.
AB - BACKGROUND/AIM: The myasthenia gravis-quality of life questionnaire 15 item (MG
QOL15) is a validated, short, and easy to use disease-specific quality of life
(QOL) tool in myasthenia gravis. Other than Turkish, a lot of versions of the MG
QOL15 have been used in different languages in different cultures. Therefore, the
aim of this study was to translate and construct a validated and adapted Turkish
version of the MG-QOL15 [MG-QOL15(T)]. MATERIALS AND METHODS: After translation,
back-translation, and comparison of the 2 English versions of the MG-QOL15, it
was tested by 22 monolingual healthy individuals and then 23 patients with
clinically stable MG. Afterwards, 11 voluntary patients out of these 23 patients
were interviewed for a second time. During the second interview, the MG-QOL15(T)
and the 36-item short-form health survey (Turkish version) were administered
simultaneously. RESULTS: The MG-QOL15(T) was found to have high internal
consistency (1st and 2nd evaluation Cronbach's alphas were 0.958 and 0.928,
respectively), test-retest reliability, and concurrent validity. The MG-QOL15(T)
was negatively correlated with physical functioning, general health, vitality,
and social functioning domains and with the physical and mental composite scores
of the SF-36. CONCLUSION: The MG-QOL15(T) is accepted to be a valid, reliable,
valuable tool for measuring disease-specific QOL in Turkish patients with MG.
PMID- 27513413
TI - Sleep quality and factors affecting sleep in elderly patientswith rheumatoid
arthritis in Turkey.
AB - BACKGROUND/AIM: Sleep disorders are more common in people with rheumatoid
arthritis (RA). We aimed to determine the sleep quality in adult and elderly
people with RA and the factors associated with sleep disorders in each group.
MATERIALS AND METHODS: The study was conducted with 182 patients (83 elderly and
99 adult patients) diagnosed with RA. Data were collected through a patient
identification form including sociodemographic and disease characteristics. The
Health Assessment Questionnaire (HAQ) and Pittsburg Sleep Quality Index (PSQI)
were used to assess quality of life and sleep. RESULTS: The mean PSQI scores of
the elderly group were lower than those of adult subjects (P = 0.055). Patients
in remission and those with knee involvement had significantly lower PSQI scores
(P < 0.05). Mean PSQI scores of elderly single patients and subjects with sleep
disorders and restless leg syndrome were significantly higher (P < 0.05). In
elderly subjects, the pain and HAQ scores were positively correlated with the
PSQI. CONCLUSION: Sleep quality of elderly rheumatoid arthritis patients was
determined to be worse than that of adults; however, the difference was not
statistically different. Factors negatively affecting sleep included pain, joints
involved, high disease activity, and restless leg syndrome.
PMID- 27513414
TI - The effectiveness of a back school program in lowerlimb amputees: a randomized
controlled study.
AB - BACKGROUND/AIM: A few studies have been carried out in lower limb amputees (LLAs)
and they examined the incidence of and reasons for low back pain. The aim of this
study was to assess the effectiveness of a back school program in LLAs with
mechanical low back pain (MLBP). MATERIALS AND METHODS: Forty male unilateral
transfemoral amputees with MLBP were randomly allocated into two groups. A back
school program was applied to Group 1 over 2 weeks. A booklet for home use was
given to each participant in Group 2. Pain was assessed using a visual analogue
scale. Spinal flexibility measurements were obtained. For the assessment of back
pain-related disability, the Oswestry Disability Index was used. Patients were
assessed at baseline, at month 1, and at month 3. RESULTS: At the month 1
assessment, a reduction in pain intensity and disability, and increase in spinal
flexibility measurements were detected in Group 1 only (P < 0.05). At the month 3
assessment, there were improvements in all measured parameters in both groups(P <
0.05). Group 1 had better results in all parameters compared with Group 2.
CONCLUSION: The back school program, combined with an exercise program, decreased
pain and disability and improved the spinal flexibility significantly in LLAs
with MLBP.
PMID- 27513415
TI - N-terminal-pro brain natriuretic peptide levels in children with allergic
rhinitis.
AB - BACKGROUND/AIM: Persistent upper airway obstruction may lead to increased
pulmonary arterial pressure (PAP). The aim of this study was to evaluate N
terminal pro brain natriuretic peptide (NT-proBNP) concentrations and PAP values
in children with allergic rhinitis. MATERIALS AND METHODS: Sixty-six patients
with allergic rhinitis and 22 healthy children were prospectively enrolled in
this study. Plasma NT-proBNP levels were measured at first admission and after
treatment. Simultaneously, echocardiography was done to assess pulmonary arterial
hypertension, and rhinitis symptom scores were recorded. RESULTS: The median age
of the study group was 9.0 (5.0-17.0) years; 26 were female. PAP was found to be
normal in all the patients. There was a negative correlation between age and NT
proBNP levels (r = -0.452, P < 0.01). Nasal blockage levels affected NT-proBNP
levels mildly (P = 0.067). No significant difference between before and after
nasal steroid treatment was observed in NT-proBNP levels. CONCLUSION: These
results suggest that NT-proBNP level and PAP may not be affected in children with
allergic rhinitis, and primarily this influence may be associated with the
severity of nasal obstruction.
PMID- 27513416
TI - ILP-2 modeling and virtual screening of an FDA-approved library:a possible
anticancer therapy.
AB - BACKGROUND/AIM: The members of the inhibitors of apoptosis protein (IAP) family
inhibit diverse components of the caspase signaling pathway, notably caspase 3,
7, and 9. ILP-2 (BIRC-8) is the most recently identified member of the IAPs,
mainly interacting with caspase 9. This interaction would eventually lead to
death resistance in the case of cancerous cells. Therefore, structural modeling
of ILP-2 and finding applicable inhibitors of its interaction with caspase 9 are
a compelling challenge. MATERIALS AND METHODS: Three main protein modeling
approaches along with various model refinement measures were harnessed to achieve
a reliable 3D model, using state-of-the-art software. Thereafter, the selected
model was employed to perform virtual screening of an FDA approved library.
RESULTS: A model built by a combinatorial approach (homology and ab initio
approaches) was chosen as the best model. Model refinement processes successfully
bolstered the model quality. Virtual screening of the compound library introduced
several high affinity inhibitor candidates that interact with functional residues
of ILP2. CONCLUSION: Given the 3D structure of the ILP2 molecule, we found
promising inhibitory molecules. In addition to high affinity towards the ILP2
molecule, these molecules interact with residues that play pivotal rules in ILP2
caspase interaction. These molecules would inhibit ILP2-caspase interaction and
consequently would lead to reactivated cell apoptosis through the caspases
pathway.
PMID- 27513417
TI - Higher neutrophil to lymphocyte ratio is related to a lower ejectionfraction in
bicuspid aortic valve patients.
AB - BACKGROUND/AIM: Inflammation plays an important role in the pathophysiology of
vascular disease. In this study, we aimed to evaluate the associations of
neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) with left
ventricular ejection fraction and ascending aorta diameter in patients with a
bicuspid aortic valve (BAV). MATERIALS AND METHODS: One hundred and thirty-nine
consecutive patients with the diagnosis of BAV were enrolled in the study.
Complete blood counts were analyzed for neutrophil and lymphocyte levels and NLR.
The subjects were separated into two groups based on their ascending aorta
diameter. The patients with ascending aorta diameter equal to or above 3.9 cm
were included in group 1 whereas those with ascending aorta diameter below 3.9 cm
were included in group 2. RESULTS: When the results were compared, it was
demonstrated that there was a positive correlation between NLR and ascending
aorta diameter (r: 0.485, P = 0.026), whereas there was a negative correlation
between NLR and left ventricular end-diastolic diameter (r: 0.475, P = 0.030),
left ventricular end-systolic diameter (r: 0.482, P = 0.027), and left
ventricular ejection fraction (r: -0.467, P = 0.033) in BAV patients with
ascending aorta dilatation (group 1). CONCLUSION: NLR is associated with
ascending aorta diameter and left ventricular ejection fraction in BAV patients
with ascending aorta dilatation.
PMID- 27513418
TI - Do patients with neurogenic bladder treated with clean
intermittentcatheterization need antibacterial prophylaxis?
AB - BACKGROUND/AIM: In this study, we investigated the effectiveness of antibiotic
prophylaxis (ABP) with respect to the incidence of symptomatic urinary tract
infections (UTIs) and evaluated the development of renal scarring in patients
treated with clean intermittent catheterization (CIC). MATERIALS AND METHODS: A
total of 22 patients were included in the study. The patients were administered
ABP in the first year (the ABP-received period) but not in the second year (the
ABP-discontinued period). RESULTS: Twenty-eight of all cultures taken in the ABP
received period (18.2%) and 25 (16.2%) of the ABP-discontinued cultures were
considered to be indicative of symptomatic UTIs (P = 0.65). The multiple
antibiotic resistance rate of microorganisms in cultures taken during the ABP
discontinued period (47; 30.5%) was lower than that in those taken in the ABP
received period (62; 40.3%), (P = 0.07). There was no difference between the ABP
received and ABP-discontinued periods with respect to the development of new
lesions according to dimercaptosuccinic acid results (P = 0.14). CONCLUSION:
Routine ABP usage is not protective against the development of symptomatic UTIs
and new lesions in neurogenic bladder patients receiving CIC. Furthermore, the
growth of resistant microorganisms increased in the ABP-received period.
PMID- 27513419
TI - Transesophageal echocardiography experience in thepediatric age group in a
tertiary cardiac center.
AB - BACKGROUND/AIM: The aim of this study was to evaluate the transesophageal
echocardiography (TEE) findings of pediatric patients in a tertiary center where
complex congenital heart surgery and interventional procedures have been
performed. MATERIALS AND METHODS: All TEE studies performed between December 2009
and December 2014 were reviewed retrospectively. Patients were divided into 3
groups: perioperative, during interventional procedures, and due to other
reasons. Demographic features, transthoracic echocardiography (TTE) reports, TEE
reports, change in decision after TEE evaluation, and related complications were
recorded. RESULTS: A total of 703 patients who had TEE evaluation were included
in the study; 51% were female and 49% were male. The median age was 90 months (2
months to 18 years). TEE was performed perioperatively in 430 patients (61%),
during cardiac catheterization-angiography and electrophysiology studies in 181
patients (26%), and due to other reasons in 92 patients (13%). Mismatches between
TTE and TEE or changes in decision after TEE evaluation were present in 45
patients (10.4%) who had perioperative TEE, in 10 patients (5.5%) who had TEE
during interventional procedures, and 22 patients (24%) who had TEE evaluation
due to other reasons. No major complications were detected. CONCLUSION:
Information acquired by TEE increases the clarity of future plans for the patient
and helps to decrease the mortality and morbidity caused by unnecessary
procedures.
PMID- 27513420
TI - The effects of pulmonary hypertension on early outcomes inpatients undergoing
coronary artery bypass surgery.
AB - BACKGROUND/AIM: To investigate the effects of pulmonary hypertension on early
clinical variables in patients undergoing coronary artery bypass grafting
surgery. MATERIALS AND METHODS: The preoperative echocardiographic data of
patients who underwent isolated coronary artery bypass surgery were evaluated
retrospectively. A total of 1244 patients were included in the study. The
patients were divided into two groups: one group consisted of patients with
systolic pulmonary artery pressure (SPAP) values equal to or greater than 30 mmHg
(Group 1, n = 184), while the other group consisted of patients with SPAP values
below 30 mmHg (Group 2, n = 1060). RESULTS: Early mortality was similar in both
groups (0% in Group 1 and 1.2% in Group 2; P > 0.05). Comparison of postoperative
data indicated that Group 1 had a higher need for inotropic agent treatment, a
longer average duration of ventilation, and a longer average duration of stay in
the intensive care unit (P < 0.05). For the other variables, no significant
differences were identified between patients with and without pulmonary
hypertension (P > 0.05). CONCLUSION: Mild pulmonary hypertension (mean SPAP =
37.7 +/- 8.4 mmHg) was not associated with a significant difference in the
mortality of patients undergoing coronary artery bypass grafting. For patients
undergoing this type of coronary bypass surgery, lower morbidity and mortality
rates can be achieved through comprehensive preoperative examinations and
effective perioperative medical procedures.
PMID- 27513421
TI - Proliferation and differentiation markers of colorectal adenocarcinomaand their
correlation with clinicopathological factors.
AB - BACKGROUND/AIM: The purpose of this study was to investigate proliferation and
differentiation markers in colorectal adenocarcinoma and their correlation with
clinicopathological factors. MATERIALS AND METHODS: Samples were collected from
38 patients with colorectal adenocarcinoma and 10 healthy controls. E-cadherin,
carcinoembryonic antigen (mCEA), cyclin B1, vascular endothelial growth factor
(VEGF), and erythropoietin (EPO) receptor (EPOR) were examined by
immunohistochemistry; VEGF and EPO were examined by real-time PCR. RESULTS: The
tumor samples were mostly characterized by large dimension (pT3), moderate level
of differentiation (G2), negative lymph node status (N0), and no metastasis.
Cyclin B1 and VEGF gene and protein expressions were significantly higher in
tumor tissues than in control tissues; E-cadherin expression was significantly
decreased in tumor samples and in positive correlation with mCEA. EPO was almost
undetectable in tumor tissues of colorectal adenocarcinoma. Significant positive
correlation was detected between tumor size and cyclin B1, tumor grade, and lymph
node status. CONCLUSION: Decreased expression of EPO, high levels of VEGF and
cyclin B1 expression, predominant moderate tumor differentiation, absence of
metastasis, and negative lymph node status may suggest low level of
aggressiveness, better prognosis, and longer patient survival.
PMID- 27513422
TI - RETRACTED ARTICLE: DNA profiling in blood, buccal swabs, and hair follicles of
transplantation patients.
PMID- 27513423
TI - Correlation of Ki-67 proliferation index and 18-fluorodeoxyglucose uptake in
colorectal incidental lesions detected by positron emission tomography-computed
tomography.
AB - BACKGROUND/AIM: To investigate whether focal high maximum standardized uptake
value (SUVmax) determined by 18-fluorodeoxyglucose (FDG) positron emission
tomography (PET)-computed tomography (CT) imaging is correlated with
proliferation index in the colorectal region. MATERIALS AND METHODS: SUVmax
values of 31 colorectal neoplasms that were incidentally detected during PET-CT
examination were compared to dysplasia degree, histopathologic diagnosis, and
immunohistochemical expression of the Ki-67 proliferation marker. RESULTS:
Statistically significant correlations were found between SUVmax and Ki-67
proliferation index, dysplasia degree, and histopathologic diagnosis. Median
SUVmax value was found to be significantly higher in high-risk lesions than low
risk lesions. CONCLUSION: The Ki-67 proliferation index is an indicator of SUVmax
in colorectal tract. SUVmax values can predict malignancy and prognosis in this
region. Colonoscopy and biopsy should always be performed whenever a focal high
FDG uptake is determined incidentally in a patient.
PMID- 27513424
TI - The inhibitory effect of bacteriocin produced by Lactobacillus acidophilusATCC
4356 and Lactobacillus plantarum ATCC 8014 on planktonic cells and biofilms of
Serratia marcescens.
AB - BACKGROUND/AIM: The spread of antibiotic-resistant pathogens has resulted in the
need for new treatments. The aim of the present study is to investigate the
effect of bacteriocin from Lactobacillus acidophilus ATCC 4356 and Lactobacillus
plantarum ATCC 8014 on planktonic and biofilm forms of Serratia marcescens
strains. MATERIALS AND METHODS: The direct antagonism of the L. plantarum and L.
acidophilus cell-free supernatant on S. marcescens cultures was determined using
an optical density assay. The bacteriocin was partial purified by ammonium
sulfate precipitation. Its molecular weight was analyzed with sodium dodecyl
sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The effect of bacteriocins
on the biofilm of S. marcescens strains was then determined with 2,3,5-triphenyl
tetrazolium chloride. RESULTS: The purified bacteriocin from L. plantarum ATCC
8014 and partially purified bacteriocin from L. acidophilus ATCC 4356 displayed
noticeable inhibitory activity against planktonic and biofilm forms of S.
marcescens strains. SDS-PAGE analysis revealed that the apparent molecular weight
of bacteriocin from L. planetarium was 63 kDa, and that of bacteriocin from L.
acidophilus was 68 or 48 kDa. CONCLUSION: The bacteriocins could be effective
compounds to control surface-attached pathogenic bacteria and can be used as
therapeutic agents after acceptable in vivo experimentation.
PMID- 27513425
TI - Expression of maspin in testis tumors with germ cells andits relation with
angiogenesis factors.
AB - BACKGROUND/AIM: We aimed to evaluate the importance of maspin expression in
testicular tumors with germ cells, its effect on prognosis, and the relation with
angiogenesis factors. MATERIALS AND METHODS: The paraffin blocks of the
orchiectomy materials of 32 patients who had undergone orchiectomy due to
testicular tumors were taken within the scope of the study. The specimens of the
cases included in the study group were reexamined under light microscope.
RESULTS: While just one maspin-positive sample was found in the seminoma cases,
maspin stained positively in 6 of the nonseminoma germ cell tumors (NSGCTs). No
statistical difference was found between maspin and tumor stage, size, alpha
fetoprotein values, vascular endothelial growth factor, Ki-67, and CD31. A
statistically positive correlation was only determined between maspin and p53 (P
< 0.001). CONCLUSION: Maspin protein, whose expression in some tumors is accepted
as a poor prognostic factor, is also expressed in testicular tumors with germ
cells. However, according to our study, it is difficult to say whether this
protein is a favorable or poor prognostic factor in testicular tumors and to
understand how the effect mechanism works. The positive correlation between
maspin and p53 in the NSGCTs makes us think that maspin might have displayed an
effect on the p53 pathway.
PMID- 27513426
TI - Effects of resveratrol and cigarette smoking onbone healing: histomorphometric
evaluation.
AB - BACKGROUND/AIM: The aim of the present study is to investigate the effects of
cigarette smoke (CS) and simultaneous application of resveratrol on bone healing
histomorphometrically and to evaluate the effects of resveratrol on negative
effects of CS. MATERIALS AND METHODS: For 4 weeks, Sprague Dawley rats were
exposed to cigarette smoke at the equivalent of 6 cigarettes per day. After this
period, monocortical defects were created in femurs by a trephine bur on day 28.
Starting from the day of defect creation to the 28th postoperative day, rats were
given 20 mg/kg body weight resveratrol. Histomorphometric examination of the
number of osteoblasts and osteoclasts, as well as new bone area, was conducted.
RESULTS: Investigations were carried out on 33 rats. Differences between
osteoblast numbers in the control and CS groups were significant, and CS caused a
reduction in the number of osteoblasts. Areas of new bone formation in the
resveratrol and control groups were higher than in the smoking and
smoking+resveratrol groups. CONCLUSION: Smoking appeared to have adverse effects
upon bone healing and resveratrol administration helped to reduce these effects.
PMID- 27513427
TI - Effects of 1-(2-trifluoromethylphenyl)-imidazole (TRIM) on receptor-independent
and -dependent contractile responses in rat aorta.
AB - BACKGROUND/AIM: This study investigates whether 1-(2-trifluoromethylphenyl)
imidazole (TRIM), originally proposed as a nitric oxide synthase inhibitor and
also suggested to be an inhibitor of store-operated calcium entry in mouse
anococcygeal muscle, inhibits receptor-independent and -dependent responses in
rat thoracic aorta. MATERIALS AND METHODS: Cyclopiazonic acid- and serotonin
induced vascular responses were investigated in aortic segments isolated from
male Sprague Dawley rats using isolated tissue experiments. Changes in
intracellular calcium levels were also monitored via front surface fluorescence
measurements in fura-2-loaded embryonic rat vascular smooth muscle cell line
A7r5. RESULTS: TRIM inhibited serotonin-mediated vascular contractions without
affecting cyclopiazonic acid-induced responses. In addition, TRIM caused a
nonlinear rightward shift in the serotonin concentration-response curve, possibly
via serotonin receptor modulation. CONCLUSION: TRIM may have an impact on
investigation of tissue-specific receptor-independent and -dependent vascular
responses. It may also be used as a lead compound in the development of selective
serotonin receptor modulators.
PMID- 27513428
TI - The effect of low-dose methotrexate on autologous fat graft survival.
AB - BACKGROUND/AIM: The survival of autologous fat graft tissue is dependent on
various factors such as vascularization and inflammation. The aim of the present
study was to evaluate the possible beneficial effects of low-dose methotrexate
(LD-MTX) on fat graft volume and survival. MATERIALS AND METHODS: A total of 13
male Wistar albino rats were divided into two groups, a control group and an LD
MTX group. An autologous fat graft obtained from the inguinal region of each rat
was transferred to its back. LD-MTX was administered intraperitoneally in the LD
MTX group once a week for 4 weeks after the surgical procedure. The control group
underwent surgery but was not administered MTX. Fat grafts were harvested for
analyses. RESULTS: The results showed that 2 months postoperatively the fat graft
weights of the control and LD-MTX groups were not significantly different. In
addition, the vascularity of the grafts was higher in the LD-MTX group than it
was in the control group. The mean lipid peroxidation levels were essentially the
same in the two groups, but myeloperoxidation was significantly lower in the LD
MTX group than it was in the other group. CONCLUSION: The results showed that LD
MTX administration may not preserve the quality and volume of transplanted fat
tissue in rats.
PMID- 27513429
TI - The beneficial effects of almond (Prunus amygdalus Batsch) hull on serum lipid
profile and antioxidant capacity in male rats.
AB - BACKGROUND/AIM: Almond hull is produced in high amounts and mostly used as
livestock feed. This study was designed to examine the impact of almond hull
powder (AHP) administration on lipid profile and antioxidant activities in plasma
and liver in hyperlipidemic rats. MATERIALS AND METHODS: As the first step, the
antioxidant capacity and radical scavenging activity of AHP were determined using
calorimetric methods. Then 36 adult male Wistar rats were randomly divided into 6
groups: group 1 with oral administration of 10% AHP, group 2 with oral
administration of 20% AHP, group 3 with oral administration of 30% AHP, group 4
as a positive control with a high cholesterol diet, group 5 as a negative control
with a normal diet, and group 6 as a sham group with a normal diet and 20% AHP.
The rats were fed a hypercholesterolemic diet to create a hyperlipidemia rat
model and then they received AHP for 30 days. RESULTS: Antioxidant and radical
scavenging activity of the AHP extract showed a high content of antioxidants that
exert potent radical scavenging activity. According to the results obtained, upon
the administration of AHP the levels of cholesterol and triglycerides
significantly decreased, while the antioxidant capacity of plasma increased.
CONCLUSION: AHP with bioactive compounds and fiber can reduce total cholesterol
and triglycerides and improve serum antioxidant capacity.
PMID- 27513430
TI - Effects of cepae extract, allantoin, and heparin mixture on developing andalready
formed epidural fibrosis in a rat laminectomy model.
AB - BACKGROUND/AIM: The study was designed to investigate whether local
administration of a mixture composed of cepae extract, allantoin, and heparin
(CAH) decreased already formed epidural fibrosis (EF) at the laminectomy site.
MATERIALS AND METHODS: Twenty-four adult male Sprague Dawley rats were equally
divided into four groups. Laminectomy was performed at the L5 level in all rats.
The group 2 and group 4 rats were treated with local drug administration. While
the group 1 and 2 rats were sacrificed after 6 weeks, the remaining rats were
reoperated and CAH mixture was applied in group 4. The vertebral columns of all
rats were removed en bloc. Fibroblast numbers, EF, and arachnoidal involvement
(AI) were evaluated. RESULTS: The results of the treatment groups were separately
compared with the control groups. The numbers of fibroblasts in the treatment
groups were significantly lower than those in the control groups (P < 0.001). The
grade of EF in group 2 was significantly less than that in group 1 (P < 0.05).
There was no statistically significant difference regarding EF and AI grade
between group 3 and group 4, and local application of the drug on EF and AI
yielded better results than in the control groups. CONCLUSION: The mixture
composed of CAH might be a successful candidate for preventing EF in clinical
practice.
PMID- 27513431
TI - The consequences of aluminium intake on reproductive function in male rats:a
three-generation study.
AB - BACKGROUND/AIM: The effects of aluminium exposure on reproductive biomarkers in
male rats were followed in a three-generation study. MATERIALS AND METHODS: Forty
Wistar male rats (F0) were divided into the following groups: control (C),
receiving only tap water, and three experimental (E) groups, receiving aluminium
sulphate (AS) (E1: 200 ppb, E2: 400 ppb, and E3: 1000 ppb) in drinking water for
a 6-month exposure period. To obtain F1, three males from each group were mated
with previously unexposed females (1:2 sex ratios) that during gestation and
lactation were exposed to the same AS levels as males. The F1 generation male
offspring were divided as described and exposed to the same AS levels. The
protocol to obtain F2 was similar to that described for F1. RESULTS:
Significantly lower testosterone levels in rats exposed to AS and in generations
F1 and F2 compared to the parental one, luteinising hormone (LH) fluctuations in
F0 and a significant LH decrease in F2 and F3 generations, testis weight
decrease, increased immobile and abnormal sperm, and histoarchitecture
alterations in the testes were observed. Moreover, interval between deliveries
increased. CONCLUSION: Chronic exposure to AS was significantly deleterious,
producing a pronounced decrease in the sperm count and testosterone levels in all
experimental groups.
PMID- 27513432
TI - The effects of novokinin, an AT2 agonist, on blood pressure, vascular responses,
and levels of ADMA, NADPH oxidase, and Rho kinase in hypertension induced by NOS
inhibition and salt.
AB - BACKGROUND/AIM: The effects of AT2 receptor agonist novokinin on blood pressure,
eNOS, NADPH oxidase, protein arginine methyltransferases (PRMTs), and Rho kinase
in hypertension were investigated. Furthermore, in isolated thoracic aorta rings,
contractile and dilator responses were studied. MATERIALS AND METHODS: To develop
hypertension, L-NAME was administered intraperitoneally and salt was given with
tap water (1%) for 4 weeks. Novokinin was administered intraperitoneally for the
last 2 weeks. Blood pressures were measured using the tail-cuff method and enzyme
levels by real-time polymerase chain reaction in aortic tissues. RESULTS: Blood
pressure increased significantly in hypertensive rats. Novokinin reduced the
blood pressure in the hypertensive group. While the contractile responses to
increasing doses of angiotensin II were increased, vascular reactivity (Emax) and
sensitivity (EC50) to acetylcholine were decreased in hypertensive rats. In
novokinin-treated hypertensive groups, the EC50 value decreased and the Emax
value for acetylcholine significantly increased. The levels of Rho kinase and
PRMT expression increased and the level of eNOS expression decreased in the
hypertensive group. In novokinin-treated rats, ADMA, NADPH oxidase, and Rho
kinase tended to decreased, but these changes did not reach statistical
significance. CONCLUSION: Although further studies are needed to determine its
effectiveness, the AT2 agonist novokinin may be a novel agent that is promising
in terms of protective effects for the treatment of hypertension.
PMID- 27513433
TI - Effectiveness of a single versus repeated administration of trimetazidine in the
protection against warm ischemia/reperfusion injury of rat liver.
AB - BACKGROUND/AIM: The aim of this study was to compare the effects of single and
repeated trimetazidine (TMZ) administration against warm hepatic
ischemia/reperfusion (I/R) injury and to explore the possible mechanisms affected
by TMZ. MATERIALS AND METHODS: Wistar rats were divided into 4 groups (n = 6).
Sham: rats were subjected to dissection. I/R: rats were subjected to 60 min of
partial hepatic ischemia followed by 24 h of reperfusion. TMZ1: Same as I/R group
but rats were pretreated with a single dose of TMZ (10 mg/kg, intraperitoneal
injection) 30 min before warm ischemia. TMZ3: Same as I/R but rats were treated
with 10 mg/kg TMZ for 3 successive days. RESULTS: TMZ treatment decreased liver
injury, lipid peroxidation, and apoptosis. The repeated administration of TMZ
conferred more protection than the single dose treatment concerning all studied
parameters. In parallel, we noted a significant increase in phosphorylated
adenosine monophosphate activated protein kinase (p-AMPK) and endothelial nitric
oxide synthase (eNOS) levels in TMZ3 as compared to TMZ1. CONCLUSION: Repeated
administration of TMZ for 3 days was more efficient than a single dose of TMZ in
protecting the liver against I/R induced apoptosis and lipid peroxidation. These
effects implicate AMPK and eNOS activation.
PMID- 27513434
TI - Effects of naloxone and yohimbine in polycystic ovary syndrome: a rabbit model
study.
AB - BACKGROUND/AIM: To assess the therapeutic effects of naloxone and yohimbine on
polycystic ovary syndrome (PCOS) in a rabbit model in terms of body weight and
endocrinological parameters (luteinizing hormone, insulin, and estradiol).
MATERIALS AND METHODS: A total of 50 adult, reproductively mature female rabbits
(Oryctolagus cuniculus) were divided into five groups (n = 10/group). In the
control group PCOS was not induced (negative control group), whereas in the
remaining four groups (n = 40) PCOS was induced with a single i.m. injection of
testosterone daily and were designated as follows: positive control, naloxone
treated (NalT), yohimbine-treated (YohT), and naloxone+yohimbine-treated (NalYT)
groups. RESULTS: A steadily ascending trend was noted in all of the studied
parameters in the PCOS-induced group as compared to the negative control group.
All the parameters showed a descending trend in the NalT group as compared to the
positive control. Regarding the YohT and NalYT groups, all parameters showed a
descending trend as compared to the positive control group except for estradiol.
CONCLUSION: Naloxone therapy either alone or combined with yohimbine improves a
wide range of the clinical manifestations of PCOS. Furthermore, we suggest this
therapy as an alternative to the conventional therapy with insulin-lowering
agents in vogue.
PMID- 27513435
TI - Serum lithium levels are associated with white blood cell counts in bipolar
disorder.
PMID- 27513436
TI - The importance of coronary angiography for ischemic sign confirmationdetected by
myocardial perfusion scintigraphy.
PMID- 27513437
TI - Herbal self-medication use in Type 2 diabetes mellitus.
PMID- 27513439
TI - Synthesis of Photo- and pH Dual-Sensitive Amphiphilic Copolymer PEG43-b-P(AA76-co
NBA35-co-tBA9) and Its Micellization as Leakage-Free Drug Delivery System for UV
Triggered Intracellular Delivery of Doxorubicin.
AB - Novel photo- and pH dual-sensitive amphiphilic copolymers containing photolabile
o-nitrobenzyl (NB) groups were designed via combination of ATRP, hydrolyzation,
and simple esterification reaction and self-assembled into stimuli-regulated
amphiphilic micelles in aqueous solution. On the basis of the optimization of the
morphology and particle size of the micelles via modulating the number of the
photocleavable o-nitrobenzyl acrylate (NBA) units, the unique ones assembled from
PEG43-b-P(AA76-co-NBA35-co-tBA9) with an average hydrodynamic diameter (Dh) of
163 nm was selected as a potential drug delivery system (DDS) for UV-triggered
delivery of doxorubicin (DOX). The micelles possessed a favorable drug-loading
capacity (DLC) of 27.5%, with the hydrodynamic diameter of 213 nm after DOX
loading. Most importantly, the DOX-loaded PEG43-b-P(AA76-co-NBA35-co-tBA9)
micelles exhibited a cumulative DOX release ratio of only 3.69% in the simulated
physiological medium within 6 days without UV-irradiation, indicating their
potential as leakage-free DDS. As in the acidic media mimicking the tumor
microenvironment, a high cumulative DOX release ratio of 74.70% was achieved
within 6 days after UV-irradiation for 20 min, showing a sustained release
behavior. Under UV-irradiation, the photolabile o-nitrobenzyl moieties were
cleaved off, the amphiphilic copolymer transformed into a water-soluble polymer,
favoring the metabolism of drug carriers, and the micelles were demicellized to
accelerate the drug release in a triggered or on-demand manner.
PMID- 27513438
TI - Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus
infection.
AB - BACKGROUND: Rhinovirus (RV) infection in asthma induces varying degrees of airway
inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear.
OBJECTIVE: The major goal was to determine the role of genetic variation [e.g.
single nucleotide polymorphisms (SNPs)] of Toll-interacting protein (Tollip) in
airway epithelial responses to RV in a type 2 cytokine milieu. METHODS: DNA from
blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA,
AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors
without lung disease were cultured to determine pro-inflammatory and antiviral
responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged
with house dust mite (HDM) and infected with RV1B to determine lung inflammation
and antiviral response. RESULTS: Asthmatic subjects carrying the AG or GG
genotype (AG/GG) compared with the AA genotype demonstrated greater airflow
limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16
treatment, cells with AG/GG (vs. AA) produced more IL-8 and expressed less
antiviral genes, which was coupled with increased NF-kappaB activity and
decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co
localized and interacted with LC3. Inhibition of autophagy decreased antiviral
genes in IL-13- and RV16-treated cells. Upon HDM and RV1B, Tollip knockout (vs.
wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and
viral load, but lower levels of antiviral gene expression. CONCLUSIONS AND
CLINICAL RELEVANCE: Our data suggest that Tollip SNP rs5743899 may predict
varying airway response to RV infection in asthma.
PMID- 27513440
TI - Tissue fibrosis: a pathomechanistically unresolved challenge and scary clinical
problem.
PMID- 27513442
TI - Oxytocin and behavior: Lessons from knockout mice.
AB - It is well established that the nonapeptide oxytocin (Oxt) is important for the
neural modulation of behaviors in many mammalian species. Since its discovery in
1906 and synthesis in the early 1950s, elegant pharmacological work has helped
identify specific neural substrates on which Oxt exerts its effects. More
recently, mice with targeted genetic disruptions of the Oxt system-i.e., both the
peptide and its receptor (the Oxtr)-have further defined Oxt's actions and laid
some important scientific groundwork for studies in other species. In this
article, we highlight the scientific contributions that various mouse knockouts
of the Oxt system have made to our understanding of Oxt's modulation of behavior.
We specifically focus on how the use of these mice has shed light on our
understanding of social recognition memory, maternal behavior, aggression, and
several nonsocial behaviors. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol
77: 190-201, 2017.
PMID- 27513443
TI - Competitive colonization of prosthetic surfaces by staphylococcus aureus and
human cells.
AB - Implantation of a biomaterial provides an adhesion substratum both to host cell
integration and to contaminating bacteria. We studied simultaneous competitive
adhesion of Staphylococcus aureus in serial 1:10 dilutions of 108 colony forming
units (CFU)/mL and human osteogenic sarcoma (SaOS-2) or primary osteoblast (hOB)
cells, both 1x105 cells/mL, to the surfaces of titanium, polydimethylsiloxane and
polystyrene. The bacterial adherence and human cell proliferation, cytotoxicity
and production of reactive oxygen species (ROS) were studied using fluorometric
(fluorescent microscopy and flow cytometry) and colorimetric methods (MTT, LDH
and crystal violet). The bacterial cell viability was also evaluated using the
drop plate method. The presence of bacteria resulted in reduced adherence of
human cells to the surface of the biomaterials, increased production of ROS, and
into increased apoptosis. On the other hand, the presence of either type of human
cells was associated with a reduction of bacterial colonization of the
biomaterial with Staphylococcus aureus. These results suggest that increasing
colonization of the biomaterial surface in vitro by one negatively affects
colonization by the other. Host cell integration to an implant surface reduces
bacterial contamination, which opens novel opportunities for the design of
infection-resistant biomaterials in current implantology and future regenerative
medicine. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 62
72, 2017.
PMID- 27513444
TI - Rethinking the Pregnancy Planning Paradigm: Unintended Conceptions or
Unrepresentative Concepts?
PMID- 27513446
TI - What Happens after Activation of Ascaridole? Reactive Compounds and Their
Implications for Skin Sensitization.
AB - To replace animal testing and improve the prediction of skin sensitization,
significant attention has been directed to the use of alternative methods. The
direct peptide reactivity assay (DPRA), the regulatory agencies' approved
alternative in chemico method, has been applied for understanding the
sensitization capacity of activated ascaridole. Ascaridole, the oxidative
metabolite of alpha-terpinene, is considered to be one of the components
responsible for the contact allergy associated with essential oils derived from
Chenopodium and Melaleuca species. The recently developed high-throughput
screening based on the dansyl cysteamine (HTS-DCYA) method was applied to
understand the reported enhanced reactivity of activated ascaridole and possibly
to identify the resulting elusive radical or other reactive species. For the
first time, a substituted cyclohexenone was identified as a potential
electrophilic intermediate resulting in higher depletion of nucleophilic DCYA,
along with several nonreactive byproducts of ascaridole via a radical degradation
mechanism. Formation of electrophilic species via radical degradation is one of
the possible pathways should be considered for the peptide reactivity of in aged
tea tree oil or oils rich in terpinenes along with commonly believed reactants,
allylic-epoxides and allylic-peroxides.
PMID- 27513447
TI - Three-dimensional imaging of shear bands in bulk metallic glass composites.
AB - The mechanism of the increase in ductility in bulk metallic glass matrix
composites over monolithic bulk metallic glasses is to date little understood,
primarily because the interplay between dislocations in the crystalline phase and
shear bands in the glass could neither be imaged nor modelled in a validated way.
To overcome this roadblock, we show that shear bands can be imaged in three
dimensions by atom probe tomography from density variations in the reconstructed
atomic density, which density-functional theory suggests being a local-work
function effect. Imaging of near-interface shear bands in Ti48 Zr20 V12 Cu5 Be15
bulk metallic glass matrix composite permits measurement of their composition,
thickness, branching and interactions with the dendrite interface. These results
confirm that shear bands here nucleate from stress concentrations in the glass
due to intense, localized plastic deformation in the dendrites rather than
intrinsic structural inhomogeneities.
PMID- 27513445
TI - The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype.
AB - The RAD51 protein plays a key role in the homology-directed repair of DNA double
strand breaks and is important for maintaining genome stability. Here we report
on a novel human RAD51 variant found in an aggressive and therapy-refractive
breast carcinoma. Expression of the RAD51 G151D variant in human breast
epithelial cells increases the levels of homology-directed repair. Expression of
RAD51 G151D in cells also promotes high levels of chromosomal aberrations and
sister chromatid exchanges. In vitro, the purified RAD51 G151D protein directly
and significantly enhances DNA strand exchange activity in the presence of RPA.
In concordance with this result, co-incubation of G151D with BRCA2 resulted in a
much higher level of strand-exchange activity compared to WT RAD51. Strikingly,
the RAD51 G151D variant confers resistance to multiple DNA damaging agents,
including ionizing radiation, mitomycin C, and doxorubicin. Our findings
demonstrate that the RAD51 G151D somatic variant has a novel hyper-recombination
phenotype and suggest that this property of the protein is important for the
repair of DNA damage, leading to drug resistance.
PMID- 27513448
TI - The impact of obesity on outcomes and complications after top-down retropubic
midurethral sling.
AB - AIMS: Obese women (BMI >= 30 kg/m2 ) have been considered at higher risk for
postoperative complications and failure in efficacy after SUI surgery. We compare
the outcomes in this population with non-obese women (BMI < 30 kg/m2 ) undergoing
top-down retropubic polypropylene midurethral sling (RPM). METHODS: We
retrospectively identified 328 non-obese women and 294 obese women who underwent
RPM. Evaluation included SEAPI (stress incontinence, emptying, anatomy,
protection, inhibition) assessment and validated QoL questionnaires. Cure was
defined as absence of subjective and objective SUI and no additional procedures
to correct SUI. Perioperative details were abstracted from the hospital and
clinic charts. Groups and outcomes were statistically compared. RESULTS: All
women had a minimum follow up of 12 months. Preoperative demographic variables,
SEAPI scores, and QoL indices were similar between BMI groups. SUI cure rates
were significantly higher for non-obese women (82.9% vs. 74.5%; P < 0.01). When
controlling for concomitant pelvic surgery, cure rates were not statistically
different (76.9% vs. 73.7%; P = 0.65). Statistically significant improvement in
SEAPI scores and QoL indices was achieved in both groups. Overall, obese women
had no increase in complications compared with the non-obese. The chance of
passing an initial postoperative voiding trial was statistically higher in the
obese group. CONCLUSIONS: Obese women have similar success rates and significant
improvement in QoL as non-obese women after RPM. Obesity alone does not appear to
be a risk factor for additional complications during sling surgery and obese
women may have earlier return to normal voiding after surgery.
PMID- 27513450
TI - Rapid Identification of the Receptor-Binding Specificity of Influenza A Viruses
by Fluorogenic Glycofoldamers.
AB - The re-emergence of influenza raises a global concern that viral pandemics can
unpredictably occur. However, effective approaches that can probe the infection
risk of influenza viruses for humans are rare. In this work, we develop a
glycofoldamer that can rapidly identify the glycan-receptor specificity of
influenza viruses in a high-throughput manner. The coupling of glycan receptors
that can be recognized by hemagglutinin (a surface protein on the virion capsid
of influenza) to a fluorogenic-dye foldamer produces the glycofoldamers with
minimal fluorescence in aqueous solution. After interaction with human-infecting
virus strains for only five minutes, the fluorescence intensity of the
glycofoldamer is remarkably enhanced with a blue-shifted emission peak. The
probes have also proven effective for the rapid identification of 1) the human-
or bird-infecting properties of influenza viruses in a high-throughput manner and
2) the receptor-specificity switch of a virus strain by mutations.
PMID- 27513449
TI - The RNA-Binding Protein, Polypyrimidine Tract-Binding Protein 1 (PTBP1) Is a Key
Regulator of CD4 T Cell Activation.
AB - We have previously shown that the RNA binding protein, polypyrimidine tract
binding protein (PTBP1) plays a critical role in regulating the expression of
CD40L in activated CD4 T cells. This is achieved mechanistically through message
stabilization at late times of activation as well as by altered distribution of
CD40L mRNA within distinct cellular compartments. PTBP1 has been implicated in
many different processes, however whether PTBP1 plays a broader role in CD4 T
cell activation is not known. To examine this question, experiments were designed
to introduce shRNA into primary human CD4 T cells to achieve decreased, but not
complete ablation of PTBP1 expression. Analyses of shPTB-expressing CD4 T cells
revealed multiple processes including cell proliferation, activation-induced cell
death and expression of activation markers and cytokines that were regulated in
part by PTBP1 expression. Although there was an overall decrease in the steady
state level of several activation genes, only IL-2 and CD40L appeared to be
regulated by PTBP1 at the level of RNA decay suggesting that PTBP1 is critical at
different regulatory steps of expression that is gene-specific. Importantly, even
though the IL-2 protein levels were reduced in cells with lowered PTBP1, the
steady-state level of IL-2 mRNA was significantly higher in these cells
suggesting a block at the translational level. Evaluation of T cell activation in
shPTB-expressing T cells revealed that PTBP1 was linked primarily to the
activation of the PLCgamma1/ERK1/2 and the NF-kappaB pathways. Overall, our
results reveal the importance of this critical RNA binding protein in multiple
steps of T cell activation.
PMID- 27513452
TI - The effect of pain on task switching: pain reduces accuracy and increases
reaction times across multiple switching paradigms.
AB - Pain disrupts attention, which may have negative consequences for daily life for
people with acute or chronic pain. It has been suggested that switching between
tasks may leave us particularly susceptible to pain-related attentional
disruption, because we need to disengage our attention from one task before
shifting it onto another. Switching tasks typically elicit lower accuracies
and/or longer reaction times when participants switch to a new task compared with
repeating the same task, and pain may exacerbate this effect. We present 3
studies to test this hypothesis. In study 1, participants completed 2 versions of
an alternating runs switching task under pain-free and thermal pain-induction
conditions. Pain did not affect performance on either task. In studies 2 and 3,
we examined 7 versions of the switching task using large general population
samples, experiencing a variety of naturally occurring pain conditions, recruited
and tested on the internet. On all tasks, participants with pain had longer
reaction times on both switch and repeat trials compared with participants
without pain, but pain did not increase switch costs. In studies 2 and 3, we also
investigated the effects of type of pain, duration of pain, and analgesics on
task performance. We conclude that pain has a small dampening effect on
performance overall on switching tasks. This suggests that pain interrupts
attention even when participants are engaged in a trial, not only when attention
has been disengaged for shifting to a new task set.
PMID- 27513453
TI - Nudix Effectors: A Common Weapon in the Arsenal of Plant Pathogens.
PMID- 27513454
TI - Gait in children and adolescents with Charcot-Marie-Tooth disease: a systematic
review.
AB - Symptoms of Charcot-Marie-Tooth (CMT) disease typically arise in childhood or
adolescence with gait difficulty most common. A systematic review was conducted
to synthesise, review, and characterise gait in paediatric CMT. Health-related
electronic databases were reviewed with search terms related to CMT and gait. Of
454 articles, 10 articles describing seven studies met eligibility criteria;
samples ranged from 1 to 81, included mixed CMT sub-types and had a participant
mean age of 13 years. Assessments included a variety of methods to examine only
barefoot gait. Heterogeneity of gait patterns was noted. Children and adolescents
with CMT walked slower, most likely due to shorter stride length. Common
kinematic and kinetic abnormalities included significant foot drop during swing,
reduced calf muscle power, and proximal compensatory mechanisms in the lower
limb. Little data were found to inform typical functional gait characteristics or
change over time. Of note, barefoot assessment does not reflect function in
everyday life where footwear is commonly worn. With limited existing literature,
future studies of gait in paediatric CMT need to evaluate the influence of
diagnostic sub-types and disease progression; the effect of factors such as
footwear and the environment; and to explore changes in gait and function
throughout childhood and adolescence.
PMID- 27513455
TI - RAMP1 suppresses mucosal injury from dextran sodium sulfate-induced colitis in
mice.
AB - BACKGROUND AND AIMS: Calcitonin gene-related peptide (CGRP) is thought to be
involved in the modulation of intestinal motility. CGRP receptor is composed of
receptor activity-modifying protein (RAMP) 1 combined with calcitonin receptor
like receptor (CRLR) for CGRP. The study investigated the role of CGRP in mice
with experimentally induced colitis. METHODS: The study used dextran sodium
sulfate (DSS) to induce colitis in mice. The study compared the severity of
colitis in wild-type (WT) mice, mice treated with a CGRP receptor antagonist
(CGRP8-37 ), and RAMP1 knockout (-/- ) mice. Pathological changes in the mucosa
were assessed, and inflammatory cells and cytokine levels were measured. RESULTS:
The severity of inflammation in DSS-induced colitis increased markedly in CGRP8
37 -treated mice and RAMP1-/- mice compared with WT mice. RAMP1-/- mice showed
more severe damage compared with CGRP8-37 -treated mice. The number of periodic
acid-Schiff-positive cells decreased in CGRP8-37 -treated mice compared with WT
mice and was even further decreased in RAMP1-/- mice. RAMP1 was expressed by
macrophages, mast cells, and T-cells. RAMP1-/- mice exhibited excessive
accumulation of macrophages and mast cells into the colonic tissue with increased
levels of tumor necrosis factor-alpha and interleukin-1beta as compared with WT
mice. Infiltration of T-cells into the colonic mucosa, which was associated with
the expression of T helper (Th) cytokines including Th1 (interferon gamma) and
Th17 (IL-17), was augmented in RAMP1-/- mice. CONCLUSIONS: The findings of this
study suggest that RAMP1 exerted mucosal protection in DSS-induced colitis via
attenuation of recruitment of inflammatory cells and of pro-inflammatory
cytokines.
PMID- 27513456
TI - The next generation of novel therapies for the management of relapsed multiple
myeloma.
AB - The advent of various novel therapies such as immunomodulators and proteasome
inhibitors has transformed the treatment paradigm for patients with multiple
myeloma (MM). As a result, the overall survival has improved dramatically over
the last decade. Despite these advances, MM remains mostly incurable and most
patients experience disease relapse after enjoying a period of disease control or
remission. Fortunately, the scientific community continues to make strides in
developing 'next-generation' therapies for the management of patients with
relapsed MM. This review will summarize the efficacy of some of the newest
therapeutic agents available for the treatment of patients with relapsed MM after
their upfront treatment with the original novel agents such as thalidomide,
lenalidomide and bortezomib.
PMID- 27513458
TI - Concerted Rattling in CsAg5 Te3 Leading to Ultralow Thermal Conductivity and High
Thermoelectric Performance.
AB - Thermoelectric (TE) materials convert heat energy directly into electricity, and
introducing new materials with high conversion efficiency is a great challenge
because of the rare combination of interdependent electrical and thermal
transport properties required to be present in a single material. The TE
efficiency is defined by the figure of merit ZT=(S(2) sigma) T/kappa, where S is
the Seebeck coefficient, sigma is the electrical conductivity, kappa is the total
thermal conductivity, and T is the absolute temperature. A new p-type
thermoelectric material, CsAg5 Te3 , is presented that exhibits ultralow lattice
thermal conductivity (ca. 0.18 Wm(-1) K(-1) ) and a high figure of merit of
about 1.5 at 727 K. The lattice thermal conductivity is the lowest among state-of
the-art thermoelectrics; it is attributed to a previously unrecognized phonon
scattering mechanism that involves the concerted rattling of a group of Ag ions
that strongly raises the Gruneisen parameters of the material.
PMID- 27513459
TI - Geography of Genetic Structure in Barley Wild Relative Hordeum vulgare subsp.
spontaneum in Jordan.
AB - Informed collecting, conservation, monitoring and utilization of genetic
diversity requires knowledge of the distribution and structure of the variation
occurring in a species. Hordeum vulgare subsp. spontaneum (K. Koch) Thell., a
primary wild relative of barley, is an important source of genetic diversity for
barley improvement and co-occurs with the domesticate within the center of
origin. We studied the current distribution of genetic diversity and population
structure in H. vulgare subsp. spontaneum in Jordan and investigated whether it
is correlated with either spatial or climatic variation inferred from publically
available climate layers commonly used in conservation and ecogeographical
studies. The genetic structure of 32 populations collected in 2012 was analyzed
with 37 SSRs. Three distinct genetic clusters were identified. Populations were
characterized by admixture and high allelic richness, and genetic diversity was
concentrated in the northern part of the study area. Genetic structure, spatial
location and climate were not correlated. This may point out a limitation in
using large scale climatic data layers to predict genetic diversity, especially
as it is applied to regional genetic resources collections in H. vulgare subsp.
spontaneum.
PMID- 27513460
TI - Alkali Metal Hydridotriphenylborates [(L)M][HBPh3] (M = Li, Na, K):
Chemoselective Catalysts for Carbonyl and CO2 Hydroboration.
AB - Light alkali metal hydridotriphenylborates M[HBPh3] (M = Li, Na, K),
characterized as tris{2-(dimethylamino)ethyl}amine (L) complexes [(L)M][HBPh3],
act as efficient catalysts for the chemoselective hydroboration of a wide range
of aldehydes and ketones using pinacolborane HBpin. The lithium derivative showed
a remarkably high TOF of >=17 s(-1). These compounds also catalyze the
hydroborative reduction of CO2 to give formoxyborane HCO2Bpin without any over
reduction.
PMID- 27513457
TI - Role of Proteome Physical Chemistry in Cell Behavior.
AB - We review how major cell behaviors, such as bacterial growth laws, are derived
from the physical chemistry of the cell's proteins. On one hand, cell actions
depend on the individual biological functionalities of their many genes and
proteins. On the other hand, the common physics among proteins can be as
important as the unique biology that distinguishes them. For example, bacterial
growth rates depend strongly on temperature. This dependence can be explained by
the folding stabilities across a cell's proteome. Such modeling explains how
thermophilic and mesophilic organisms differ, and how oxidative damage of highly
charged proteins can lead to unfolding and aggregation in aging cells. Cells have
characteristic time scales. For example, E. coli can duplicate as fast as 2-3
times per hour. These time scales can be explained by protein dynamics (the rates
of synthesis and degradation, folding, and diffusional transport). It
rationalizes how bacterial growth is slowed down by added salt. In the same way
that the behaviors of inanimate materials can be expressed in terms of the
statistical distributions of atoms and molecules, some cell behaviors can be
expressed in terms of distributions of protein properties, giving insights into
the microscopic basis of growth laws in simple cells.
PMID- 27513463
TI - Total Synthesis of Anticancer Agent EBC-23.
AB - Total synthesis of spiroketal EBC-23 has been described by two divergent
approaches from three simple building blocks. Gold-catalyzed cycloisomerization
of alkynol and acid-mediated spirocyclization of diketalketone were successfully
utilized to effect spiroketal formation. A Cu(I)-P(Cy)3-catalyzed protocol for
the highly regio- and stereocontrolled hydroboration of internal propargylic
alcohol was effectively applied toward the beta-hydroxy ketone via
vinylboronates.
PMID- 27513462
TI - MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma
Derived Cells.
AB - Osteosarcoma is the most common primary bone tumor and poor prognosis for
osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are
important to maintain pathophysiological mechanisms of cancer and influence cell
sensitivity to chemotherapy. In this study, we tested the functions of microRNA
21 for malignant features as well as for drug resistance of osteosarcoma. We used
Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines.
MicroRNA-21 activity was modulated by either expressing a sponge to decrease its
activity in an osteosarcoma-derived cell line expressing high levels of microRNA
21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels.
Cell migration was determined in a scratch assay and cell proliferation was
measured by performing growth curve analysis. Sensitivity of the cells towards
chemotherapeutics was investigated by performing cell viability assays and
calculating the IC50 values. While cell migration was unaffected by modulated
microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously
expressed microRNA-21 promoted this process. Modulated microRNA-21 activity
failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or
methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced
resistance towards cisplatin while ectopic expression of microRNA-21 showed the
opposite effect. Increased microRNA-21 levels repressed the expression of
Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the
observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate
that in osteosarcoma microRNA-21 expression is an important component for
regulation of cell proliferation and for determining sensitivity to cisplatin.
PMID- 27513464
TI - Developmental Origins of Disease - Crisis Precipitates Change.
AB - The concept of developmental origins of diseases has gained a huge interest in
recent years and is a constantly emerging scientific field. First observations
hereof originated from epidemiological studies, linking impaired birth outcomes
to adult chronic, noncommunicable disease. By now there is a considerable amount
of both epidemiological and experimental evidence highlighting the impact of
early life events on later life disease susceptibility. Albeit far from being
completely understood, more recent studies managed to elucidate underlying
mechanisms, with epigenetics having become almost synonymous with developmental
programming. The aim of this review was to give a comprehensive overview of
various aspects and mechanisms of developmental origins of diseases. Starting
from initial research foci mainly centered on a nutritionally impaired
intrauterine environment, more recent findings such as postnatal nutrition,
preterm birth, paternal programming and putative interventional approaches are
summarized. The review outlines general underlying mechanisms and particularly
discusses mechanistic explanations for sexual dimorphism in developmental
programming. Furthermore, novel hypotheses are presented emphasizing a non
mendelian impact of parental genes on the offspring's phenotype.
PMID- 27513465
TI - WNT2 Promotes Cervical Carcinoma Metastasis and Induction of Epithelial
Mesenchymal Transition.
AB - BACKGROUND: Previously, we found an 11-gene signature could predict pelvic lymph
node metastasis (PLNM), and WNT2 is one of the key genes in the signature. This
study explored the expression and underlying mechanism of WNT2 in PLNM of
cervical cancer. METHODS: WNT2 expression level in cervical cancer was detected
using western blotting, quantitative PCR, and immunohistochemistry. Two WNT2
specific small interfering RNAs (siRNAs) were used to explore the effects of WNT2
on invasive and metastatic ability of cancer cells, and to reveal the possible
mechanism of WNT2 affecting epithelial-mesenchymal transition (EMT). The
correlation between WNT2 expression and PLNM was further investigated in clinical
cervical specimens. RESULTS: Both WNT2 mRNA and protein expression was
upregulated in cervical cancer. High WNT2 expression was significantly associated
with tumor size, lymphovascular space involvement, positive parametrium, and most
importantly, PLNM. PLNM and WNT2 expression were independent prognostic factors
for overall survival and disease-free survival. WNT2 knockdown inhibited SiHa
cell motility and invasion and reversed EMT by inhibiting the WNT2/beta-catenin
pathway. WNT2 overexpression in cervical cancer was associated with beta-catenin
activation and induction of EMT, which further contributed to metastasis in
cervical cancer. CONCLUSION: WNT2 might be a novel predictor of PLNM and a
promising prognostic indicator in cervical cancer.
PMID- 27513466
TI - Longitudinal Evaluation of Segmental Arterial Mediolysis in Splanchnic Arteries:
Case Series and Systematic Review.
AB - BACKGROUND: Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic,
non-inflammatory vascular disorder varying widely in clinical course. The purpose
of this study is to analyze detailing clinical and imaging manifestations over
time in patients with SAM through a literature review and to suggest an optimal
management strategy. METHODS: A retrospective review of eight consecutive
patients diagnosed with SAM between January, 2000 and January, 2012 was
conducted. All presented with acute-onset abdominal or flank pain. Clinical
features, imaging studies, and laboratory findings served as grounds for
diagnosis, having excluded more common conditions (ie, fibromuscular dysplasia,
collagen vascular disorders, or arteritis). CT angiography was done initially and
repeated periodically (Week 1, Month 3, then yearly). Treatment was conservative,
utilizing endovascular intervention as warranted by CT diagnostics. In a related
systematic review, all English literature from 1976 to 2015 was screened via the
PubMed database, assessing patient demographics, affected arteries, clinical
presentations, and treatment methods. FINDINGS: Ultimately, 25 arterial lesions
identified in eight patients (median age, 62.8 years; range, 40-84 years) were
monitored for a median period of 26 months (range, 15-57 months). At baseline,
celiac axis (3/8, 37.5%), superior mesenteric (4/8, 50%), and common hepatic
(2/8, 25%) arteries were involved, in addition to isolated lesions of right
renal, splenic, right colic, middle colic, gastroduodenal, left gastric, right
gastroepiploic, proper hepatic, right hepatic, and left hepatic arteries.
Compared with prior publications, celiac axis and superior mesenteric artery were
more commonly affected in cohort. Arterial dissections (n = 8), aneurysms (n =
5), stenoses or occlusions (n = 4), and a single pseudoaneurysm were documented.
Despite careful conservative management, new splanchnic arterial lesions (n = 4)
arose during follow-up. Considering the few available reports of new arterial
lesions in the literature, newly developing pathology is a distinctive feature of
our patients, four of whom eventually required endovascular interventions.
CONCLUSIONS: Careful clinical observation via periodic CT angiography is required
in patients with SAM, checking for newly developing lesions. The natural history
of SAM should be clarified in a larger patient population.
PMID- 27513469
TI - Botulinum toxin therapy in Frey's syndrome: a retrospective study of 440
treatments in 100 patients.
AB - OBJECTIVE: Frey's syndrome is characterised as sweating, redness and warmth of
the parotideal area and is often treated with botulinum toxin A. The objective of
this retrospective study was to prove whether the toxin dosage and time-to
treatment intervals change after repeated botulinum toxin injections. STUDY
DESIGN/METHODS: The charts of patients, who were treated for Frey's syndrome
during the last 16 years, were assessed. Three brands of botulinum toxin A were
available for therapy. The Minor test was used to confirm the sweating before
each treatment and to determine the toxin dosage. Constant amount of botulinum
toxin was injected per cm2 of the affected area. Patients consulted our
department for the next treatment as soon as they felt disturbed by recurring
sweating and when the sweating was objectively evident in the Minor test. Time
intervals between treatments and injected toxin dosages were assessed. RESULTS:
In total, 100 patients received 440 treatments in 16 years. Repeated injections,
median 4.0, were carried out in 70.5% of patients. Median time interval to the
first injection was 2.8 years. Median time interval between treatments was 12.0
months and showed to be steady (anova, P = .49, F = 1.01). CONCLUSION: Duration
of effect of botulinum toxin on Frey's syndrome was long-lasting and stable with
no significantly different time intervals between treatments. The extent of the
sweating area did not vary significantly after repeated treatments and required a
constant dose of botulinum toxin A.
PMID- 27513467
TI - Brains of Native and Alien Mesocarnivores in Biomonitoring of Toxic Metals in
Europe.
AB - Mercury (Hg), lead (Pb) and cadmium (Cd) are involved in mammalian brain damage.
However, little is known about Pb and Cd brain levels in wildlife that reflect
the geochemical background. The aims of the study include the estimation of Hg,
Pb and Cd concentrations, and the determination of relationships between these
elements in the brains of 94 mesocarnivores. Road-killed or hunted animals were
obtained from north-western Poland near the Polish-German border. The
investigation covered the native Eurasian otter Lutra lutra, badger Meles meles,
pine marten Martes martes, beech marten M. foina, European polecat Mustela
putorius, red fox Vulpes vulpes, and alien species: feral and ranch American mink
Neovison vison, raccoon Procyon lotor and raccoon dog Nyctereutes procyonoides.
Depending on the diet and environmental pollution, the carnivore brains
accumulated toxic metals in varying amounts. The highest median Hg levels (in
mg/kg dry weight, dw) were found in the piscivorous Eurasian otter and feral mink
(2.44 and 3.96), Pb in the omnivorous raccoon (0.47), while Cd in minks (~0.06).
We indicated that Pb-based ammunition is a significant source of the element in
scavengers from hunting area, and we also found a significant correlation between
Pb and Cd levels in the fox brain. Finally, this study is the first to suggest
background levels for brain Pb and Cd in mesocarnivores (<0.50 and <0.04 mg/kg
dw, respectively).
PMID- 27513470
TI - Overexpression of long non-coding RNA MFI2 promotes cell proliferation and
suppresses apoptosis in human osteosarcoma.
AB - The long non-coding RNA MFI2 antisense RNA is overexpressed in human cancer
tissues and its increased expression is associated with occurrence and metastasis
of cancer. However, the underlying mechanism in evolution and progression of
human osteosarcoma is not well known. In the present study, we aimed to evaluate
the molecular mechanism of lncRNA MFI2 in promoting osteosarcoma cell
proliferation and suppressing apoptosis. We found that the lncRNA MFI2 was
significantly overexpressed in human osteosarcoma tissues. Knockdown of lncRNA
MFI2 expression suppressed MG63 and SAOS-2 cell proliferation, migration and
invasion, and induced cell apoptosis. Furthermore, the expression of forkhead box
P4 (FOXP4) was significantly increased and it was positively associated with
lncRNA MFI2 expression in tumor tissues. In addition, knockdown of FOXP4
expression by RNA interference strategy inhibited osteosarcoma cell
proliferation, migration and invasion, and promoted cell apoptosis. All the
results indicated lncRNA MFI2 could promote proliferation and migration of
osteosarcoma cells by regulating FOXP4 expression, which suggested critical roles
of lncRNA MFI2 and FOXP4 in occurrence and development of human osteosarcoma.
PMID- 27513471
TI - Population-Based Incidence Rates of First-Ever Stroke in Central Vietnam.
AB - INTRODUCTION: Stroke incidence data with methodologically acceptable design in
Southeast Asia countries is limited. This study aimed to determine incidence of
age-, sex- and subtype-specific first-ever stroke (FES) in Vietnam. METHODS: We
conducted a hospital-based retrospective study, targeting all stroke cases
hospitalized at a solo-provider hospital in our study site of Nha Trang from
January 2009 to December 2011 with International Classification of Diseases, 10th
revision (ICD-10) codes I60-69. We calculated positive predictive values (PPVs)
of each ICD-10-coded stroke by conducting a detailed case review of 190 randomly
selected admissions with ICD-10 codes of I60-I69. These PPVs were then used to
estimate annual incident stroke cases from the computerized database. National
census data in 2009 was used as a denominator. RESULTS: 2,693 eligible admissions
were recorded during the study period. The crude annual incidence rate of total
FES was 90.2 per 100,000 population (95% CI 81.1-100.2). The age-adjusted
incidence of FES was 115.7 (95% CI 95.9-139.1) when adjusted to the WHO world
populations. Importantly, age-adjusted intracerebral hemorrhage was as much as
one third of total FES: 36.9 (95% CI 26.1-51.0). CONCLUSIONS: We found a
considerable proportion of FES in Vietnam to be attributable to intracerebral
hemorrhage, which is as high or exceeding levels seen in high-income countries. A
high prevalence of improperly treated hypertension in Vietnam may underlie the
high prevalence of intracerebral hemorrhagic stroke in this population.
PMID- 27513472
TI - MixMC: A Multivariate Statistical Framework to Gain Insight into Microbial
Communities.
AB - Culture independent techniques, such as shotgun metagenomics and 16S rRNA
amplicon sequencing have dramatically changed the way we can examine microbial
communities. Recently, changes in microbial community structure and dynamics have
been associated with a growing list of human diseases. The identification and
comparison of bacteria driving those changes requires the development of sound
statistical tools, especially if microbial biomarkers are to be used in a
clinical setting. We present mixMC, a novel multivariate data analysis framework
for metagenomic biomarker discovery. mixMC accounts for the compositional nature
of 16S data and enables detection of subtle differences when high inter-subject
variability is present due to microbial sampling performed repeatedly on the same
subjects, but in multiple habitats. Through data dimension reduction the
multivariate methods provide insightful graphical visualisations to characterise
each type of environment in a detailed manner. We applied mixMC to 16S microbiome
studies focusing on multiple body sites in healthy individuals, compared our
results with existing statistical tools and illustrated added value of using
multivariate methodologies to fully characterise and compare microbial
communities.
PMID- 27513473
TI - SRCIN1 Suppressed Osteosarcoma Cell Proliferation and Invasion.
AB - SRCIN1 (SRC kinase signalling inhibitor 1) is a new tumor suppressor gene.
Previous studies showed that SRCIN1 played a tumor suppressor role in the
development of lung cancer and breast cancer. However, the role of SRCIN1 in
osteosarcoma is still unknown. In this study, we demonstrated that SRCIN1 was
downregulated in osteosarcoma cell lines compared with osteoblastic cell line.
Moreover, SRCIN1 was downregulated in osteosarcoma tissues compared with the
adjacent tissues. Further investigation revealed that overexpression of SRCIN1
inhibited the osteosarcoma cell line MG-63 proliferation. This effect was
confirmed by measuring the ki-67 and PCNA expression. SRCIN1 overexpression
promoted E-cadherin expression and suppressed N-cadherin, Vimentin and Snail
expression, suggesting that SRCIN1 overexpression inhibited EMT of the
osteosarcoma cell. In addition, ectopic expression of SRCIN1 inhibited the MG-63
cell colony formation and invasion. These data suggested that SRCIN1 acted as a
tumor suppressor gene in the development of osteosarcoma.
PMID- 27513474
TI - Is One Trial Sufficient to Obtain Excellent Pressure Pain Threshold Reliability
in the Low Back of Asymptomatic Individuals? A Test-Retest Study.
AB - The assessment of pressure pain threshold (PPT) provides a quantitative value
related to the mechanical sensitivity to pain of deep structures. Although
excellent reliability of PPT has been reported in numerous anatomical locations,
its absolute and relative reliability in the lower back region remains to be
determined. Because of the high prevalence of low back pain in the general
population and because low back pain is one of the leading causes of disability
in industrialized countries, assessing pressure pain thresholds over the low back
is particularly of interest. The purpose of this study study was (1) to evaluate
the intra- and inter- absolute and relative reliability of PPT within 14
locations covering the low back region of asymptomatic individuals and (2) to
determine the number of trial required to ensure reliable PPT measurements.
Fifteen asymptomatic subjects were included in this study. PPTs were assessed
among 14 anatomical locations in the low back region over two sessions separated
by one hour interval. For the two sessions, three PPT assessments were performed
on each location. Reliability was assessed computing intraclass correlation
coefficients (ICC), standard error of measurement (SEM) and minimum detectable
change (MDC) for all possible combinations between trials and sessions. Bland
Altman plots were also generated to assess potential bias in the dataset.
Relative reliability for both intra- and inter- session was almost perfect with
ICC ranged from 0.85 to 0.99. With respect to the intra-session, no statistical
difference was reported for ICCs and SEM regardless of the conducted comparisons
between trials. Conversely, for inter-session, ICCs and SEM values were
significantly larger when two consecutive PPT measurements were used for data
analysis. No significant difference was observed for the comparison between two
consecutive measurements and three measurements. Excellent relative and absolute
reliabilities were reported for both intra- and inter-session. Reliable
measurements can be equally achieved when using the mean of two or three
consecutive PPT measurements, as usually proposed in the literature, or with only
the first one. Although reliability was almost perfect regardless of the
conducted comparison between PPT assessments, our results suggest using two
consecutive measurements to obtain higher short term absolute reliability.
PMID- 27513475
TI - Effects of a randomized gratitude intervention on death-related fear of
recurrence in breast cancer survivors.
AB - OBJECTIVE: Among the most prevalent and distressing concerns endorsed by breast
cancer survivors is fear of cancer recurrence (FOR), and one of the most salient
facets is the worry that a recurrence of cancer could cause one's death. The
primary goal of the present study was to test the effects of a brief, low-cost
gratitude intervention on overall FOR and death-related FOR, positing pursuit of
meaningful goals as a theoretically driven putative mediator. To replicate
published tests of similar gratitude-eliciting interventions, positive affect
(PA) was also considered as an outcome. METHOD: Sixty-seven women with early
stage breast cancer were randomly assigned to either a 6-week online gratitude
intervention or a 6-week online control condition. Outcomes were assessed at pre-
and posttreatment, as well as 1 month and 3 months after the end of treatment.
The mediator, meaningful goal pursuit, was measured via assessments over the 6
week intervention period. RESULTS: Results revealed that patients in the
gratitude intervention experienced a significant decrease in death-related FOR
compared to the control condition. Moreover, this effect was significantly
mediated by meaningful goal pursuit (and not by PA). The gratitude intervention
was also found to prevent declines in PA observed in the control condition.
CONCLUSIONS: Overall, findings support the notion that a brief gratitude
intervention can promote well-being and psychological adaptation to cancer by
stimulating the pursuit of meaningful goals and subsequently reducing death
related FOR. (PsycINFO Database Record
PMID- 27513476
TI - A model of parental distress and factors that mediate its link with parental
monitoring of youth diabetes care, adherence, and glycemic control.
AB - OBJECTIVE: Parental monitoring of adolescents' diabetes self-care is associated
with better adherence and glycemic control (A1c). A number of parent-level
factors are associated with higher levels of parental monitoring, including lower
levels of parental distress (depressive symptoms, stress, anxiety), as well as
higher levels of parental self-efficacy for diabetes management and authoritative
parenting. Often studied in isolation, these factors may be best considered
simultaneously as they are interrelated and are associated with parental
monitoring and youth adherence. METHOD: Structural equation modeling with a cross
sectional sample of 257 parent/youth (aged 11-14) dyads: (a) examined a broad
model of parental factors (i.e., parental distress, parental diabetes self
efficacy, authoritative parenting), and (b) assessed their relation to parental
monitoring, youth adherence, and A1c. Post hoc analyses of variance (ANOVAs)
evaluated clinical implications of daily parental monitoring. RESULTS: Parental
distress was not related directly to parental monitoring. Instead less distress
related indirectly to more monitoring via higher parental self-efficacy and more
authoritative parenting which, in turn, related to better adherence and A1c.
Higher parental self-efficacy also related directly to better youth adherence and
then to better A1c. Clinically, more parental monitoring related to more daily
blood glucose checks and to better A1c (8.48% vs. 9.17%). CONCLUSIONS: A broad
model of parent-level factors revealed more parental distress was linked only
indirectly to less monitoring via lower parental self-efficacy and less
authoritative parenting. Behaviorally, more parental monitoring related to better
adherence and to clinically better A1c in adolescents. Further study of parent
level factors that relate to parental distress and monitoring of adherence
appears warranted. (PsycINFO Database Record
PMID- 27513477
TI - Brief psychological intervention in patients with cervical cancer: A randomized
controlled trial.
AB - OBJECTIVES: The diagnosis and treatment of cancer is considered a major life
stress that has potential effects on one's psychological well-being. This study
investigated the possible benefits of a brief psychological intervention based on
gratitude and mindfulness for positive and negative affect in patients with
cervical cancer and explored the potentially mediating role of rumination and
reappraisal. METHODS: A randomized controlled trial was conducted in 3 public
hospitals in China between April 2014 and December 2014. One-hundred twenty
postoperative cervical cancer patients were randomly assigned into an
intervention group or a wait-list control group. Participants completed self
report measures of positive and negative affect, rumination, and reappraisal
before and after the 4-week intervention or waiting period. The outcome effects
of the intervention were analyzed by generalized estimating equations (GEE).
Mediation analyses were performed using a nonparametric bootstrapping procedure.
RESULTS: GEE results indicated significant Time * Group interaction effects on
positive affect (B = 1.60, chi2 = 25.90, p < .001), negative affect (B = -2.13,
chi2 = 28.02, p < .001), rumination (B = -2.48, chi2 = 6.48, p = .011), and
reappraisal (B = 3.28, chi2 = 41.17, p < .001) for the intervention. The effect
of the intervention on positive and negative affect was mediated by changes in
rumination and reappraisal respectively. CONCLUSIONS: The brief psychological
intervention improved positive affect and reappraisal and reduced negative affect
and rumination in women with cervical cancer. Findings support the beneficial
effects for implementing this brief psychological intervention in oncology.
(PsycINFO Database Record
PMID- 27513478
TI - Longitudinal associations between self-regulation and health across childhood and
adolescence.
AB - OBJECTIVE: There is some evidence to suggest that one's ability to delay
gratification is associated with a lower body mass index (BMI) and slower overall
weight gain. Less is known about the role that a broader set of self-regulatory
skills, including attention focusing, inhibitory control, and impulsivity, might
play in fostering not only a healthy weight but also better overall health and
health-related behaviors such as sleep. METHOD: Participants in the National
Institute of Child Health and Human Development Study of Early Child Care and
Youth Development were followed from birth through age 15 beginning in 1991. Self
regulation was assessed when children were 4.5 years old, whereas health-related
outcomes were assessed regularly between toddlerhood and adolescence. Structural
equation modeling was used to test direct associations between self-regulation
and either physical health or sleep in childhood and adolescence. RESULTS:
Findings suggest that there are long-term benefits of self-regulation, indexed by
multiple dimensions, for children's health-related outcomes. Children with better
self-regulatory skills demonstrated smaller increases in standardized BMI scores
and maintained greater mother-reported health across childhood and adolescence.
Furthermore, better self-regulation predicted fewer sleep problems and longer
sleep duration when children were 8 and 11 but not when they were 15.
CONCLUSIONS: Early self-regulation, marked by numerous skills, appears to have
long-term benefits for children's health-related outcomes. These findings provide
some evidence that targeting childhood self-regulatory skills for improvement may
help reduce poor health-related outcomes later in life and offer important
insight into potential avenues for intervention. (PsycINFO Database Record
PMID- 27513479
TI - The Spatio-Temporal Distribution of Particulate Matter during Natural Dust
Episodes at an Urban Scale.
AB - Dust storms are a common phenomenon in arid and semi-arid areas, and their
impacts on both physical and human environments are of great interest. Number of
studies have associated atmospheric PM pollution in urban environments with
origin in natural soil/dust, but less evaluated the dust spatial patterns over a
city. We aimed to analyze the spatial-temporal behavior of PM concentrations over
the city of Beer Sheva, in southern Israel, where dust storms are quite frequent.
PM data were recorded during the peak of each dust episode simultaneously in 23
predetermined fixed points around the city. Data were analyzed for both dust days
and non-dust days (background). The database was constructed using Geographic
Information System and includes distributions of PM that were derived using
inverse distance weighted (IDW) interpolation. The results show that the daily
averages of atmospheric PM10 concentrations during the background period are
within a narrow range of 31 to 48 MUg m-3 with low variations. During dust days
however, the temporal variations are significant and can range from an hourly
PM10 concentration of 100 MUg m-3 to more than 1280 MUg m-3 during strong storms.
IDW analysis demonstrates that during the peak time of the storm the spatial
variations in PM between locations in the city can reach 400 MUg m-3. An analysis
of site and storm contribution to total PM concentration revealed that higher
concentrations are found in parts of the city that are proximal to dust sources.
The results improve the understanding of the dynamics of natural PM and the
dependence on wind direction. This may have implications for environmental and
health outcomes.
PMID- 27513480
TI - [Not Available].
AB - La deteccion de la desnutricion hospitalaria continua de plena actualidad en la
literatura medica y, a pesar de que desde hace dos decadas dejo de ser un tema
novedoso, constituye un elemento recurrente en la bibliografia y motivo de
abordajes monograficos en congresos y reuniones cientificas.
PMID- 27513481
TI - [Not Available].
AB - Introduccion: la composicion lipidica de las formulas de nutricion parenteral
(NP) se postula como posible factor de evolucion clinica.Objetivo: evaluar las
diferencias en eficacia y seguridad de dos emulsiones lipidicas en NP.Material y
metodos: estudio clinico prospectivo de pacientes posquirurgicos sometidos a NP
durante mas de 7 dias en un periodo de 2 anos. Se administraron de forma
indistinta 2 tipos de emulsiones lipidicas: enriquecida con acidos grasos omega 3
(SMOFlipid Fresenius Kabi(r)) o con acido oleico omega 9 (Clinoleic Baxter(r)).
Se analizaron variables epidemiologicas, analiticas, complicaciones infecciosas y
mortalidad.Resultados: se estudio un total de 154 pacientes con edad media de
64,36 +/- 13,73 anos, de los que 95 eran hombres (61%), 78 (51%) recibieron
SMOFlipid(r) y 76 (49%) Clinoleic(r). La estancia media fue de 16,91 +/- 4,23
dias, la duracion de la NP 9,68 +/- 3,25 dias y la mortalidad del 11%. Se
diagnosticaron 58 (37%) infecciones. No existieron diferencias significativas en
cuanto a los parametros analiticos lipidicos, hepaticos o nutricionales (medidos
al inicio y al 7.o dia) ni en su evolucion (estancia media, complicaciones
infecciosas ni mortalidad) entre los dos grupos de pacientes.Conclusion: los
pacientes sometidos a NP presentan similares caracteristicas evolutivas con
independencia de la emulsion lipidica utilizada. La bibliografia actual apunta a
un beneficio de la disminucion del aporte de acidos grasos omega 9, pero no se
han encontrado diferencias significativas entre las formulas comparadas.
PMID- 27513482
TI - [Not Available].
AB - OBJECTIVE: We investigate the influence of caloric and protein deficit on
mortality and length of hospital stay of critically ill patients. METHODS: A
cohort prospective study including 100 consecutive patients in a tertiary
intensive care unit (ICU) receiving enteral or parenteral nutrition. The daily
caloric and protein deficit were collected each day for a maximum of 30 days.
Energy deficits were divided into critical caloric deficit (>= 480 kcal/day) and
non-critical caloric deficit (<= 480 kcal/day); and in critical protein deficit
(>= 20 g/day) and non-critical protein deficit (<= 20 g/day). The findings were
correlated with hospital stay and mortality. RESULTS: The mortality rate was 33%.
Overall, the patients received 65.4% and 67.7% of the caloric and protein needs.
Critical caloric deficit was found in 72% of cases and critical protein deficit
in 70% of them. There was a significant correlation between length of stay and
accumulated caloric deficit (R = 0.37; p < 0.001) and protein deficit (R = 0.28;
p < 0.001). The survival analysis showed that mortality was greater in patients
with both critical caloric (p < 0.001) and critical protein deficits (p < 0.01).
The Cox regression analysis showed that critical protein deficit was associated
with higher mortality (HR 0.25, 95% CI 0.07-0.93, p = 0.03). CONCLUSIONS: The
incidence of caloric and protein deficit in the ICU is high. Both caloric and
protein deficits increase the length of hospital stay, and protein deficit
greater than 20 g/day is an independent factor for mortality in critical care
unit.
PMID- 27513483
TI - [Not Available].
AB - INTRODUCTION: Enteral nutrition is an important therapy for severely critically
ill patients. The timing and amount of energy have been highly debated.
OBJECTIVE: The aim of the present study was to directly compare the timing and
the caloric targets in critically ill patients. METHODS: Retrospective cohort
study conducted at a single center, comparing timing and caloric goal for
critically ill patients. Patients were stratified according to the start of
nutritional therapy (24, 48, or more than 48 h) and the amount of energy
delivered (target adequacy of previously calculated percentage in the first
week). Statistical analysis was performed using parametric and non-parametric
tests for independent samples and logistic regression. The results were expressed
as mean +/- standard deviation or incidence and percentage. RESULTS AND
DISCUSSION: There were no differences in major clinical outcomes in relation to
the achievement of percentage of caloric goal at the end of the first week of the
study. The beginning of caloric intake on the first day of hospitalization was
associated with reduced mortality in the intensive care unit, but not with
hospital mortality. The strategy of an early and limited amount of calories seems
to be associated with a better outcome. Prospective studies evaluating and
comparing these strategies are recommended.
PMID- 27513484
TI - [Not Available].
AB - BACKGROUND: The different body components may contribute to the development of
insulin resistance and type 2 diabetes mellitus. The aim of the present study was
to examine the association of fat mass and fat free mass indices with markers of
insulin resistance, independently of each other and giving, at the same time,
gender-specific information in a wide cohort of European adolescents. METHODS: A
cross-sectional study in a school setting was conducted in 925 (430 males)
adolescents (14.9 +/- 1.2 years). Weight, height, anthropometric, bioimpedance
and blood parameters were measured. Indices for fat mass and fat free mass, and
homeostatic model assessment (HOMA) were calculated. Multiple regression analyses
were performed adjusting for several confounders including fat free mass and fat
mass when possible. RESULTS: Indices of fat mass were positively associated with
HOMA (all p < 0.01) after adjusting for all the confounders including fat free
mass indices, in both sexes. Fat free mass indices were associated with HOMA, in
both males and females, after adjusting for center, pubertal status,
socioeconomic status and cardiorespiratory fitness, but the associations
disappear when including fat mass indices in the adjustment's model. CONCLUSION:
Fat mass indices derived from different methods are positively associated with
insulin resistance independently of several confounders including fat free mass
indices. In addition, the relationship of fat free mass with insulin resistance
is influenced by the amount of fat mass in European adolescents. Nevertheless,
future studies should focus not only on the role of fat mass, but also on other
body components such as fat free mass because its role could vary depending of
the level and distribution of fat mass.
PMID- 27513485
TI - [Not Available].
AB - Anorexia nervosa (AN) is the most prevalent of eating disorders in children and
adolescents, and its treatment is long and complex, involving a multidisciplinary
team. Nutritional rehabilitation and restoration of a healthy body weight is one
of the central goals in the initial stages of inpatient treatment. However,
current recommendations on initial energy requirements for these patients are
inconsistent, with a clear lack of controlled studies, available scientific
evidence and global consensus on the most effective and safe refeeding practices
in hospitalized adolescents with anorexia nervosa (AN). Conservative refeeding
recommendations have been classically established in order to prevent the
refeeding syndrome. Nevertheless, various works have recently appeared advocating
a higher initial caloric intake, without observing more complications or
refeeding syndrome, and allowing a shorter average stay. We present our
experience in the treatment of restricting AN with a conservative progressive
treatment. We have obtained good results with this approach, which was well
tolerated by patients, with no observing complications. As a consequence, the
medical team could establish a pact about the therapeutic goals with the patients
in an easier way.
PMID- 27513486
TI - [Not Available].
AB - Introduccion: el bajo peso al nacer (BPN) es un factor de riesgo para desarrollar
obesidad en la vida adulta.Objetivo: evaluar diferencias en la composicion
corporal de ninos de entre 8 y 10 anos de edad con y sin antecedente de
BPN.Metodos: fue un estudio observacional, transversal comparativo. Participaron
112 ninos (95 con adecuado peso al nacer [APN] y 17 con BPN). Se realizo
antropometria (peso, talla, circunferencias de cintura y cadera, pliegue cutaneo
de triceps [PCT] y subescapular [PCSE]).Resultados: se encontro una prevalencia
combinada del 41% para sobrepeso y obesidad en ambos grupos de estudio. El
porcentaje de grasa corporal total fue menor en las ninas con BPN (no
significativo); sin embargo, el indicador PCT-PCSE fue significativamente mas
alto (p = 0,04) que el de las ninas con APN. En contra de lo esperado, al
estratificar segun porcentaje de grasa y peso al nacer, se encontro que el grupo
con BPN presento un porcentaje de grasa bajo (p < 0,05) en comparacion con el
grupo de APN, siendo 6 veces mayor la posibilidad de que un nino con BPN presente
porcentaje de grasa total bajo a esta edad.Conclusiones: a estas edades no se
encontro mayor porcentaje de grasa en el grupo con BPN en comparacion con el de
APN; sin embargo, las ninas con BPN presentaron mayor deposicion de grasa troncal
que las de APN. La deposicion de grasa es un indicador que hay que considerar, y
no unicamente el indice de masa corporal, en la evaluacion nutricia infantil.
PMID- 27513487
TI - [Not Available].
AB - Introduccion: los supervivientes de leucemia aguda (LA) infantil presentan un
riesgo incrementado de alteraciones metabolicas y cardiovasculares que aumentan
su morbimortalidad a largo plazo.Objetivo: estimar la prevalencia de obesidad,
resistencia a la insulina, dislipemia e hipertension arterial como factores de
riesgo cardiometabolico (FRCM) en un grupo de supervivientes de LA infantil, y
analizar las posibles causas asociadas a su desarrollo.Material y metodos:
estudio observacional retrospectivo en 47 supervivientes de LA tratados en un
periodo de 4 anos, que recibieron seguimiento durante 10 anos.Resultados: el 40%
de los participantes presentaron al menos un FRCM durante el seguimiento, siendo
la dislipemia (aumento LDL) el mas frecuente (38,3%), seguido de
obesidad/sobrepeso (31,9%) y HTA sistolica (23,4%). El sexo femenino se
establecio como factor de riesgo parael desarrollo de todos ellos (RR 1,6; RR
3,16; RR 1,69; p < 0,05). Ningun superviviente desarrollo diabetes mellitus, pero
si resistencia a la insulina el 19,4%. Los pacientes con leucemias de peor
pronostico presentaron mayor riesgo de desarrollar obesidad, resistencia a la
insulina y aumento de LDL (RR 3,56; RR 4,08; RR 2,53; p < 0,05). Los pacientes
tratados con trasplante de progenitores hematopoyeticos presentaron mayor riesgo
de obesidad, aumento de LDL e HTA sistolica (RR 2,86; RR 2,39; RR 3,12; p<0,05).
La radioterapia se asocio de igual modo con un incremento de resistencia a la
insulina e hipertension arterial sistolica (RR 2,47; RR 2,53; p <
0,05).Conclusiones: existe un aumento en la prevalencia de obesidad/sobrepeso,
dislipemia, resistencia a la insulina y alteracion de la tension arterial
sistolica en supervivientes de leucemia aguda infantil a lo largo del tiempo,
especialmente en aquellos con enfermedades y tratamientos mas agresivos.
PMID- 27513488
TI - [Not Available].
AB - Objetivo: el presente estudio tuvo por objetivos: a) determinar los valores de
referencia de la condicion muscular mediante el indice general de fuerza (IGF); y
b) estudiar si el IGF esta asociado con indicadores de adiposidad en ninos y
adolescentes escolares de Bogota, Colombia.Metodos: del total de 7.268 ninos y
adolescentes (9-17,9 anos) evaluados en el estudio FUPRECOL, 4.139 (57%) fueron
mujeres. Se evaluo el IGF como marcador del desempeno muscular a partir de la
tipificacion de las pruebas de fuerza prensil (FP) y salto de longitud (SL). El
IGF se recodifico en cuartiles (Q), siendo el Q4 la posicion con mejor valor del
IGF. El indice de masa corporal (IMC), la circunferencia de cintura (CC), el
indice cintura/talla (ICT) y el porcentaje de grasa corporal (% GC) por
bioimpedancia electrica se midieron como marcadores de adiposidad.Resultados: la
edad media de los evaluados fue 12,8 +/- 2,3 anos. Se aprecia una tendencia hacia
un incremento del nivel de condicion fisica muscular en los varones conforme
aumenta la edad, y hacia la estabilidad o un ligero aumento en el caso de las
mujeres. El IGF se relacionoinversamente con el ICT y % GC en los varones (r =
0,280, r = -0,327, p < 0,01), respectivamente. Los escolares ubicados en el Q4
del IGF presentaron menores valores en marcadores de adiposidad IMC, CC, ICT y %
GC, p < 0,01, que su contraparte del Q1.Conclusion: se presentan valores de
referencia del IGF a partir de la estandarizacion de los resultados obtenidos en
la FP y SL. La evaluacion de la fuerza muscular en edades tempranas permitira
implementar programas de prevencion de riesgo cardiovascular y metabolico futuro.
PMID- 27513489
TI - [Not Available].
AB - Introduccion: la malnutricion en el anciano que ingresa en el hospital es
bastante frecuente y condiciona no solo la extension de la estancia hospitalaria,
sino el pronostico o la aparicion de otras patologias. Su valoracion puede
basarse en medidas antropometricas, parametros bioquimicosy test
nutricionales.Objetivos: valorar si la circunferencia de pantorrilla es un
indicador valido de desnutricion en el paciente anciano recien hospitalizado,
analizando la posible influencia del sexo y la edad.Material y metodos: estudio
descriptivo en 907 pacientes ancianos pluripatologicos a su ingreso en el
hospital, con una edad media de 82,13 +/- 7,08 anos. Se han realizado
determinaciones bioquimicas incluyendo recuento de linfocitos, colesterol total,
transferrina y albumina.Se aplicaron en cada paciente las escalas de cribado
nutricional MNA, NRS y VGS. Finalmente se determino la circunferencia de la
pantorrilla.Resultados: los test nutricionales muestran un porcentaje de
desnutricion medio del 75%. Los parametros bioquimicos muestran un porcentaje de
desnutricion que oscila del 63,4% al 76,7%, y la circunferencia de la pantorrilla
un 74,2%. La prevalencia de desnutricion es mayor en mujeres, independientemente
del parametro utilizado en su determinacion. El aumento en la edad,
particularmente a partir de los 85 anos, y con todos los parametros analizados,
tambien condiciona un mayor grado de desnutricion. Todos los parametros
estudiados se correlacionan con la circunferencia de la pantorrilla,
estableciendose el concepto "estar desnutrido" en el punto de corte de 29 cm,
para ambos sexos y en todos los grupos de edad (sensibilidad
99,31%).Conclusiones: un 75% de la poblacion anciana presenta desnutricion a su
ingreso en el hospital. La circunferencia de la pantorrilla es un marcador de
desnutricion en el anciano de facil determinacion y alta sensibilidad,
independiente del sexo y la edad.
PMID- 27513490
TI - [Not Available].
AB - INTRODUCTION: There are few studies assessing overall diet and food patterns of
the oldest population. OBJECTIVES: To examine food groups consumption (grams and
servings) and their compliance with the dietary guidelines in community-dwelling
very old Spanish adults. The relationship with the risk of malnutrition was also
studied. METHODS: Within the cross-sectional health study of elderly people of
Villanueva de la Canada (Madrid, Spain), in 98 non-institutionalized elders aged
>= 80 years (66% women) food consumption was calculated from a 24-hour dietary
recall and nutritional risk was assessed by Mini Nutritional Assessment (MNA).
Statistical significance was evaluated at 95% confidence level (p < 0.05).
RESULTS: Men consumed significantly higher amounts of snacks/pickles and
alcoholic beverages. The consumption of cereals/grain products (2 servings/day),
vegetables (1.5 servings/day) and meat, fish, eggs (1.4 servings/day), was below
desirable levels. As nutritional status got worse, fruit consumption was
significantly smaller (p = 0.039). Relatively weak but highly significant
correlations were found between MNA and oils/fats, fruits and alcoholic
beverages. After adjustment for energy intake, oils and fats and fruits
associations disappeared whereas a negative association between milk/dairy
products and MNA was found. CONCLUSIONS: Dietary patterns of the elderly
population of Villanueva are departing from the traditional Mediterranean diet
and though adequate consumption of fruits, milk/dairy products, oils/fats and
sugar/confectionery has been achieved, cereals/grain products, vegetables and the
meat, fish, eggs group consumption was below the desirable levels. Deterioration
of the nutritional status coincided with a reduction in the consumption of all
food groups except for ready meals and milk/dairy products whose consumption
increased. Further research on the influence of fruit, milk/dairy products, wine
and olive oil consumption on nutritional status is required.
PMID- 27513491
TI - [Not Available].
AB - INTRODUCTION: Adiponectin, an adipocyte derived peptide, has anti-inflammatory
and antiatherogenic effects, and improves insulin sensitivity. However, little is
known about dietary predictors and their interactions with lifestyle on
adiponectin concentrations, in apparently healthy young adults. OBJECTIVE: To
evaluate the associations between plasma concentrations of adiponectin with
dietary components and lifestyle in apparently healthy young adults. METHODS:
Anthropometric and body composition, systolic and diastolic blood pressure, diet
and lifestyle data of 157 healthy young adults, aged 18 and 35, were collected
and analyzed. Blood samples were collected after fasting for 12 hours to
determine adiponectin concentrations. Dietary and anthropometric indexes were
calculated and analyzed. RESULTS: Adiponectin concentrations were significantly
higher for women compared to men; and there was an indirect and significant
correlation between adiponectin concentrations with BMI. There was a significant
association between adiponectin concentrations with the healthy eating index,
calories, lipids, proteins, fibers, riboflavin, and phosphorus, among others; and
a tendency with carbohydrates and niacin. In multiple linear regression analysis,
fiber and riboflavin (r2 = 0.0928; p = 0.0013) and carbohydrates and phosphorus
were associated with the concentrations of adiponectin. The association with
carbohydrates and phosphorus suffered interaction with gender (r2 = 0.2400; p <
0.0001), as well as the association with phosphorus also suffered interaction
with physical activity (r2 = 0.1275; p = 0.0003). CONCLUSION: Plasma
concentrations of adiponectin, in healthy young adults, seem to be modulated by
components of diet depending on gender and physical activity.
PMID- 27513492
TI - [Not Available].
AB - BACKGROUND: Vaspin is a newly-identifi ed adipocytokine associated with insulin
resistance (IR). OBJECTIVE: The aim of this study was to investigate the
correlation between plasma vaspin concentrations and IR and determine whether
this association is affected by body composition, physical activity and pubertal
stage in adolescents. METHODS: Were studied 484 Brazilian adolescents aged 10-14
years whose anthropometric, clinical, biochemical, and lifestyle measurements
were analized. We evaluated the correlation between vaspin and risk factors for
IR in adolescents with normal and high body fat percentage (%BF) and did a
logistic regression to calculate the odds ratio for IR according to vaspin
quartiles sex specifi c for the sample. RESULTS: Vaspin was positively correlated
with IR in adolescents with high %BF (r = 0.23, p = 0.003). The logistic
regression analysis adjusted for sex, age, BMI, and pubertal stage showed that
adolescents in the 2nd (OR = 0.43, 95% CI = 0.23-0.80, p = 0.008) and 3rd (OR =
0.46, 95% CI = 0.25-0.85, p = 0.014) quartile of vaspin concentration had a lower
risk for IR. When the model was adjusted for %BF and physical activity, the
association remained statically signifi cant only for adolescents in the 2nd
quartile. CONCLUSION: Vaspin was correlated positively with risk factors
associated with insulin metabolism in adolescents with high %BF. Vaspin was
associated with a reduced risk of IR independently of BMI and pubertal stage and
the association was infl uenced by body fat and physical activity in these
adolescents.
PMID- 27513493
TI - [Not Available].
AB - Objetivo: el objetivo de este estudio es evaluar las propiedades psicometricas
del cuestionario de disfrute por el ejercicio fisico (PACES) en adolescentes con
sobrepeso y obesidad.Metodos: participaron 139 adolescentes con sobrepeso y
obesidad: 91 ninas (edad = 13,85 +/- 1,92 anos; indice de masa corporal [IMC] =
26,83 +/- 3,16 kg/m2) y 48 ninos (edad = 14,29 +/- 1,62 anos; IMC = 28,31 +/-
3,74 kg/m2). Para analizar el disfrute por la actividad fisica se empleo el
cuestionario Physical Activity Enjoyment Scale (PACES).Resultados: los resultados
del analisis factorial exploratorio y confirmatorio han mostrado una estructura
de dos factores; a su vez el PACES presenta una consistencia interna muy alta
(alfa de Cronbach = 0,908). La fiabilidad test-retest indica una buena
concordancia temporal (Spearman rho = 0,815, p < 0,001). Por ultimo, el PACES en
adolescentes con sobrepeso y obesidad manifiesta una validez convergente adecuada
con la intencionalidad de ser activo (MIFA), la atraccion por la actividad fisica
(CAPA), la resistencia cardiorrespiratoria y los pliegues suprailiacoy
subescapular.Conclusion: los resultados confirman que el PACES es una medida
valida y fiable del disfrute por la actividad fisica en adolescentes con
sobrepeso y obesidad. El disfrute por la actividad fisica puede ser relevante en
la participacion de los adolescentes con sobrepeso y obesidad en estas
actividades.
PMID- 27513494
TI - [Not Available].
AB - BACKGROUND: Mutation analysis has identified a G-> A transition in the promoter
region of TNF-alpha gene at position -308 (rs1800629). OBJECTIVE: The aim of our
study was to investigate the influence of polymorphism in -308 GA promoter
variant of the TNF alpha gene on metabolic response and weight loss secondary to
two hypocaloric diets. METHOD: A sample of 283 obese subjects was enrolled in a
consecutive prospective way. In the basal visit, patients were randomly allocated
during 9 months to diet HP (high protein/low carbohydrate hypocaloric diet) and
diet S (standard hypocaloric diet). RESULTS: There were no significant
differences between the positive effects on weight loss in either genotype group
with both diets. With both diets and only in wild genotype (diet HP vs. diet S),
total cholesterol (-9.1 +/- 3.4 mg/dL vs. -6.9 +/- 2.0 mg/dL; p > 0.05), LDL
cholesterol (-9.0 +/- 2.9 mg/dL vs. -6.5 +/- 2.1 mg/dL; p > 0.05) and
triglycerides (-23.1 +/- 5.1 mg/dL vs. -12.3 +/- 4.8 mg/dL; p < 0.05) decreased.
The improvement in triglycerides was higher in subjects without A allele. With
diet HP and only in wild genotype, insulin levels (-3.1 +/- 1.8 UI/L; p < 0.05)
and HOMA-R (-0.8 +/- 0.1 units; p < 0.05) decreased. CONCLUSION: Carriers of -308
GG promoter variant of TNF-alpha gene have a better metabolic response than -308
GA obese with a high protein hypocaloric diet.
PMID- 27513495
TI - [Not Available].
AB - BACKGROUND: The use of sagittal abdominal diameter (SAD) has been proposed for
screening cardio-metabolic risk factors; however, its accuracy can be influenced
by the choice of thresholds values. AIM: To determine the SAD threshold values
for cardio-metabolic risk factors in Mexican adults; to assess whether parallel
and serial SAD testing can improve waist circumference (WC) sensitivity and
specificity; and to analyze the effect of considering SAD along with WC and body
mass index (BMI) in detecting cardio-metabolic risk. METHODS: This cross
sectional study was conducted during 2012-2014 in Northeast Mexico (n = 269).
Data on anthropometric, clinical, and biochemical measurements were collected.
Sex-adjusted receiver-operating characteristic curves (ROC) were obtained using
hypertension, dysglycemia, dyslipidemia and insulin resistance as individual
outcomes and metabolic syndrome as a composite outcome. Age-adjusted odds ratios
and 95% confidence intervals (CI) were estimated using logistic regression.
RESULTS: The threshold value for SAD with acceptable combination of sensitivity
and specificity was 24.6 cm in men and 22.5 cm in women. Parallel SAD testing
improved WC sensitivity and serial testing improved WC specificity. The co
occurrence of high WC/high SAD increased the risk for insulin resistance by 2.4
fold (95% CI: 1.1-5.3), high BMI/high SAD by 4.3-fold (95% CI: 1.7-11.9) and SAD
alone by 2.2-fold (95% CI: 1.2.-4.2). CONCLUSIONS: The use of SAD together with
traditional obesity indices such as WC and BMI has advantages over using either
of these indices alone. SAD may be a powerful screening tool for interventions
for high-risk individuals.
PMID- 27513496
TI - [Not Available].
AB - Introduccion: la categorizacion del estado nutricional a traves del indice de
masa corporal (IMC) es uno de los recursos de valoracion clinica mas utilizados
en el sindrome metabolico (SM). Sin embargo, es desconocida su capacidad para
identificar las diferencias en la composicion corporal.Objetivo: determinar si
las variaciones en el estado nutricional se reflejan en la composicion corporal
en mujeres con SM e identificar la concordancia de clasificacion del riesgo
cardiometabolico entre el estado nutricional e indices antropometricos.Material y
metodos: la muestra incluyo 136 mujeres (edad 42 +/- 3,5 anos) con SM. Se evaluo
el estado nutricional, masa muscular, masa adiposa, perimetro de cintura (PC),
indice cintura-cadera (ICC) e indice cintura-estatura (ICE). Se compararon los
valores de composicion corporale indices antropometricos; adicionalmente se
determino la concordancia clasificatoria del riesgo cardiometabolico entre los
indices y el IMC.Resultados: solo la edad (p = 0,358), estatura (p = 0,209) y
porcentaje de adiposidad (p = 0,234) no mostraron diferencias significativas
entre los grupos. La mejor concordancia clasificatoria del riesgo
cardiometabolico se observo en el PC > 88 cm (94,9%) e ICE >= 0,5 (94,1%) al
categorizar el IMC en normopeso vs. exceso de peso; mientras que el PC > 88 cm
obtuvo mejor concordancia separando al grupo en normopeso-sobrepesovs. obesidad
(85,3%), aunque la sensibilidad y especificidad fueron mas homogeneas con el ICC
>= 0,85.Conclusion: el IMC no logra identificar las variaciones de la adiposidad
corporal en mujeres con SM agrupadas segun su estado nutricional. El IMC presenta
mejor sensibilidad que especificidad respecto a los indices considerados para
determinar riesgo cardiometabolico en mujeres con SM.
PMID- 27513497
TI - [Not Available].
AB - BACKGROUND: Heart failure (HF) patients develop important changes in body
composition, but only a small number of studies have evaluated the associations
between these changes and functional class deterioration in a prospective manner.
OBJECTIVE: The aim of this study was to evaluate whether changes in bioimpedance
parameters were associated with NYHA functional class deterioration over six
months. METHODS: A total of 275 chronic stable HF patients confirmed by
echocardiography were recruited. Body composition measurements were obtained by
whole body bioelectrical impedance with multiple frequency equipment (BodyStat
QuadScan 4000). We evaluated functional class using the New York Heart
Association (NYHA) classification at baseline and after six months. RESULTS:
According to our results, 66 (24%) subjects exhibited functional class
deterioration, while 209 improved or exhibited no change. A greater proportion of
patients exhibited higher extracellular water (> 5%), and these patients
developed hypervolemia, according to location on the resistance/reactance graph.
A 5% decrease in resistance/height was associated with functional class
deterioration with an OR of 1.42 (95% CI 1.01-2.0, p = 0.04). CONCLUSIONS: Body
composition assessment through bioelectrical impedance exhibited a valuable
performance as a marker of functional class deterioration in stable HF patients.
PMID- 27513498
TI - [Not Available].
AB - Introduccion: a pesar de que las caracteristicas antropometricas es uno de los
metodos utilizados dentro de la seleccion de talentos deportivos, son pocos los
estudios que han analizado el perfil morfologico del jugador de beisbol de
elite.Objetivo: analizar el perfil antropometrico de los jugadores de beisbol de
elite nacional de forma global y segun el puesto ocupado.Material y metodos:
Doscientos diecisiete jugadores de beisbol masculino (edad: 23,87 +/- 5,32 anos)
de la Division de Honor espanola participaron en el presente estudio. A todos
ellos se les clasifico segun su posicion de juego y se les realizo una valoracion
antropometrica. Posteriormente se calculo su somatotipo, composicion corporal,
indice de masa corporal (IMC) y sumatorio de seis pliegues.Resultados: los
jugadores no mostraron diferencias significativas en funcion de su posicion en el
campo en la talla, el peso, los pliegues triceps, subescapular, biceps,
supraespinal, abdominal y pierna, ni en el sumatorio de seis pliegues o el
diametro biestiloideo. Si que se encontrarondiferencias significativas en el
pliegue del muslo, perimetros del brazo contraido y pierna y diametros
biepicondileo del humero y femur. Tampoco se hallaron diferencias significativas
en el IMC, la composicion corporal o el somatotipo. Los valores de endomorfia
fueron altos, los de mesomorfia altos o medio-altos y los de ectomorfia bajos,
siendo la clasificacion del somatotipo mesoendomorfo o endomorfo-mesomorfo segun
la posicion de juego.Conclusion: existe una gran homogeneidad en el perfil
antropometrico de los jugadores de beisbol segun su posicion de juego,
diferenciandose unicamente en algunas variables antropometricas como perimetros y
diametros.
PMID- 27513499
TI - [Not Available].
AB - Introduccion: actualmente los programas de entrenamiento intervalicos de alta
intensidad parecen ser una forma de optimizar el tiempo, provocando cambios en la
composicion corporal debido a la activacion de diferentes mecanismos hormonales y
metabolicos.Objetivo: observar el efecto de cuatro semanas de entrenamiento de
esprints repetidos basados en la prueba de Wingate sobre la potencia y la
composicion corporal en adultos jovenes.Metodos: los participantes (22,4 +/- 1,8
anos) fueron asignados aleatoriamente a un grupo experimental o a un grupo
control. Antes de comenzar y al acabar el periodo experimental, a los sujetos se
les realizo una densitometria de cuerpo completo y una prueba de Wingate. El
grupo experimental realizo 12 sesiones de esprints repetidos, realizando de 3 a 6
esprints de 30 segundos con un tiempo de recuperacion de 4 minutos. El grupo
control continuo con su rutina diaria y no se le aplico ningun tipo de
intervencion.Resultados: en el grupo experimental, la potencia media y maxima
incremento un 9,4-16,5% (p < 0,001). Ademas, disminuyo la masa grasa total un
8,1% (p < 0,028) y la grasa abdominal un 10,0% (p < 0,038). El grupo control no
sufrio cambios en ninguna de las variables estudiadas.Conclusiones: cuatro
semanas de entrenamiento de esprints repetidos basados en la prueba de Wingate
con un volumen especifico de ~3 minutos por sesion y una frecuencia de 3 sesiones
por semana, muestra mejoras estadisticamente significativas en la potencia maxima
y media. Ademas, provoca cambios en la composicion corporal, principalmente en la
masa grasa total y de la zona abdominal.
PMID- 27513500
TI - [Not Available].
AB - Introduccion y objetivos: las enfermedades cardiovasculares (ECV) son la
principal causa de muerte mundial, por ello el objetivo de este estudio es
analizar los factores de riesgo de ECV en los trabajadores de la Universidad de
Alicante.Material y metodos: estudio transversal descriptivo. Muestra aleatoria
(n = 124), 46,6% mujeres y 53,4% hombres, de edades entre 25-68 anos. Recogida de
datos mediante cuestionario online autocumplimentado. VARIABLES:
sociodemograficas, peso y talla autorreferidos, consumo de tabaco, actividad
fisica, consumo diario de aceite de oliva, hortalizas-verduras, mantequilla
margarina-nata y consumo semanal de reposteria comercial y frutos secos. Se
realizo un analisis descriptivo con el paquete estadistico SPSS 19.0.Resultados:
el 12% de mujeres y el 10,5% de los hombres mayores de 44 anos presentan
obesidad; ademas, el 32% de mujeres y el 23,7% de los hombres no realizan
actividad fisica. Consume aceite de oliva a diario el total de la muestra a
estudio.Conclusion: los habitos alimentarios de los estudiados se asemejan a los
patrones dieteticos mediterraneos considerados saludables. Destacar el
cumplimiento de las recomendaciones de consumo de aceite de oliva y la
realizacion de actividad fisica habitual como protectores de las ECV. El entorno
laboral de la poblacion estudiada favorece unos habitos saludables.
PMID- 27513501
TI - [Not Available].
AB - Objetivo: asociar patrones alimentarios con la autopercepcion del estado
nutricional en estudiantes universitarios chilenos de Nutricion y
Dietetica.Material y metodos: estudio transversal en el que se evaluo a 634
estudiantes de Nutricion y Dietetica, de los cuales un 86,4% eran mujeres. A cada
alumno se le mostraron siete modelos anatomicos correspondientes a valores de
indice de masa corporal (IMC) de 18, 22, 25, 27, 30, 35 y 40 kg/m2. Cada
estudiante debia elegir el modelo con el que mejor se identificaba.
Posteriormente, se realizo la evaluacion antropometrica, se calculo el IMC real
comparandolo posteriormente con el IMC percibido, y finalmente se le aplico una
encuesta alimentaria.Resultados: se observa que los sujetos que sobreestiman su
peso presentan un menor porcentaje de cumplimiento en el consumo de frutas y
verduras al dia; en cambio, el mayor porcentaje de sujetos que sigue las
recomendaciones se encuentra en el grupo que se ve igual. Hay unaasociacion entre
una buena percepcion de la imagen corporal y el consumo de 3 o mas porciones de
frutas al dia OR = 0,554 (IC 95%; 0,360-0,852), 2 o mas porciones de verduras al
dia OR = 0,438 (IC 95%; 0,283-0,678) y un consumo de alcohol menor de una vez a
la semanaOR = 0,451 (IC 95%; 0,270-0,752).Conclusion: los estudiantes que
registran una ingesta adecuada de verduras y frutas autodefinen su alimentacion
como saludable e ideal y tienden a autopercibirse coherentemente en relacion con
su estado nutricional; ademas, estos sujetos son los que presentan una ingesta
menor de alimentos poco saludables.
PMID- 27513502
TI - [Not Available].
AB - BACKGROUND AND AIM: The prevalence of hospital malnutrition (HM) is variable,
explained by the variability of patients, the nutritional evaluation method used
among others. The aim is to determine the frequency of malnutrition in hospitals
in Latin America, and estimate its association with mortality and length of
hospital stay. METHODS: This is an analytical, observational cohort study that
included 7,973 patients of both genders, 18 and older, who provided their
consent. The survey was administered during the first three days of admission.
The nutritional status was estimated using Subjective Global Assessment (SGA) and
the Nutrition Risk Screening (NRS), body mass index (BMI), percentage of change
of weight (PCW) and co-morbidities. Serum albumin was obtained from the clinical
chart. Length of stay (LOS) and the survival status at discharge (dead or alive)
were also recorded. RESULTS: By SGA: 10.9% had severe malnutrition and 34%
moderate malnutrition. By NRS: 36.9% had nutritional risk. Univariate analysis
showed that NRS score and serum albumin were prognostic factors for mortality:
NRS 3-4 (OR: 2.3, 95% CI: 1.9-2.8), NRS 5-7 (OR: 5.8, 95% CI: 4.9-6.9), serum
albumin < 2.5 g/dl, (OR: 2.9, 95% CI: 2.2-3.8). These results were consistent and
similar to a multivariate analysis. Both NRS and serum albumin were also
independently and clinically associated to LOS. CONCLUSIONS: The prevalence of
hospital malnutrition in Latin America is high. Our results show that screening
with NRS and serum albumin can identify hospital malnutrition as well as
providing clinically relevant prognostic value.
PMID- 27513503
TI - [Not Available].
AB - INTRODUCTION: Nutrition research has traditionally promoted a nutrient-based
approach; however, to evaluate population compliance with dietary
recommendations, researchers have increasingly used dietary pattern analysis.
OBJECTIVE: To assess the relationship between dietary patterns and vitamin D and
calcium intake in an adult Mexican population. METHODS: We characterized the
dietary patterns of 8,456 men and women aged 20-80 years who were participating
in the Health Workers Cohort Study. Information on participants' sociodemographic
conditions and physical activity was collected via self-administered
questionnaires. A food frequency questionnaire was used to assess diet. In a
cross-sectional analysis, we examined dietary patterns in relation to vitamin D
and calcium consumption. RESULTS: Factor analysis revealed 3 major dietary
patterns. Pattern 1, labeled as "prudent pattern", was characterized by high
positive loads for the consumption of fresh vegetables, fresh fruits, whole
grains, oils, and legumes. The second dietary pattern, named as "dairy and fish
pattern", was positively correlated with intake of dairy foods, fish and other
seafood, milk and whole grains. Finally, dietary pattern 3 was associated with
higher intake of red meat, soft drinks, fats, eggs, white meat and alcoholic
beverages. Of these, the "dairy and fish pattern" was positively and
significantly associated with vitamin D and calcium consumption (r = 0.42, p <
0.001; and r = 0.20, p < 0.001 respectively). Conversely, the third dietary
pattern was negatively associated with vitamin D and calcium intake (r = -0.28, p
< 0.001; and r = -0.41, p < 0.001, respectively). CONCLUSIONS: In summary, our
findings show that dietary patterns represented by high consumption of milk,
dairy products, whole grains, fish are associated with higher consumption of
vitamin D and calcium in Mexican adult population. Additionally, our results
highlight the importance of following an appropriate dietary pattern to achieve
adequate consumption of nutrients.
PMID- 27513504
TI - [Not Available].
AB - Introduccion: en la actualidad existe un deficit en la evaluacion de comedores
dirigidos a ninos menores de 3 anos, a pesar de que se han realizado numerosas
intervenciones en los comedores escolares con el fin de conseguir una
alimentacion segura y adecuada.Objetivo: realizar una evaluacion nutricional de
los menus ofertados en los centros de educacion infantil de Sevilla.Material y
metodos: se evaluo la frecuencia, variedad, rotacion de alimentos, metodos
culinarios e informacion de los menus de seis centros infantiles de Sevilla. Se
valoro el aporte energetico y nutricional mediante el programa Dietowin(r) y el
metodo de pesada.Resultados: las frutas y verduras fueron deficitarias en la
mayoria de los menus, y excesivas la carne, patatas, pasta y arroz. Se observo
una escasa variedad de recetas por grupo de alimentos y no se daba una
informacion completa del menu. Sin embargo, la variedad de procesos culinarios y
la rotacion de alimentos fueron adecuadas. Aunque la energia y el aporte de
carbohidratos (~55%) se ajustaban a las necesidades, se observo un aporte
excesivo de proteinas (~19%) y deficiente de lipidos (< 30%), sobre todo de
grasas insaturadas. Respecto a los micronutrientes,solo vitamina C, E y calcio
estaban por debajo de lo recomendado.Conclusiones: los centros de educacion
infantil estan haciendo un gran esfuerzo por cumplir las recomendaciones
nutricionales, pero todavia deben disminuir el aporte proteico y aumentar las
grasas insaturadas de la dieta. Ademas, deben fomentar la oferta de frutas y
verduras, ampliar la variedad de recetas, dar mayor informacion y disminuir el
aporte de alimentos carnicos.
PMID- 27513505
TI - [Not Available].
AB - BACKGROUND: Many factors can influence an athlete to consume dietary supplements,
such as age, sex and sports, among others. Few studies regarding the prevalence
and associated factors are available for athletes, especially in developing
countries. OBJECTIVE: The aim of the study was to determine the factors
associated with the consumption of dietary supplements among Brazilian athletes.
MATERIAL AND METHODS: This is a cross-sectional study involving 182 athletes of
both sexes. The athletes answered a questionnaire containing sociodemographic and
sports information, current consumption of supplements, consumption of
pharmacological substances and information on body image disorder (Body Shape
Questionnaire) and muscle dysmorphia (Muscle Appearance Satisfaction Scale).
Analyses were performed using Pearson's Chi-squared test, the crude prevalence
ratio (PR) and Poisson regression with robust variance. RESULTS: In the bivariate
analysis, the male gender, age between 25-29 years, engaging in a remunerated
activity, consumption of pharmacological substances, body image disorder, risk of
muscle dysmorphia, power modality athletes and lack of medical care were factors
associated with supplement intake. After the regression analysis, the consumption
of supplements was associated with the male gender (PR: 1.68; 95% CI: 1.01; 2.78;
p = 0.044), use of pharmacological substances (PR: 1.77; 95 %: 1.37; 2.27; p <
0.001) and the risk of muscle dysmorphia (PR: 1.75; 95% CI: 1.37; 2.23; p <
0.001). CONCLUSIONS: The results of this research clearly demonstrate the
importance of professionals working closely with athletes to continuously monitor
their use of supplements, since it was an alimentary behavior associated with
other risk behavior (pharmacological use) as well as image disorders (muscle
dysmorphia).
PMID- 27513506
TI - [Not Available].
AB - Introduccion: la hipercolesterolemia es uno de los principales factores de riesgo
en la enfermedad cardiovascular. Los esteroles vegetales se han postulado como
agentes reguladores y beneficiosos para el control de esta.Objetivo: analizar el
efecto de los esteroles vegetales anadidos en una leche en la reduccion del
colesterol plasmatico en adultos jovenes.Metodos: ensayo clinico, controlado,
aleatorizado, doble ciego y cruzado. Los esteroles (2,24 g diarios) fueron
administrados en dos tomas de 350 ml de una leche comercial desnatada, durante
dos periodos de 3 semanas, separados por una "fase de lavado" de 2 semanas, en el
grupo experimental. Al grupo control se le administro la misma cantidad de leche
desnatada, sin esteroles. Tanto al inicio como al final de cadaperiodo de
intervencion se extrajeron muestras sanguineas. Se analizaron la composicion
corporal, habitos de salud y los siguientes marcadores sanguineos: perfil
lipidico, hematologico, inflamacion, etc.Resultados: se incluyeron 54 personas en
el estudio con una edad media de 38,8 +/- 7,3 anos. La diferencia porcentual
entre los marcadores basales y finales para el colesterol total, colesterol-LDL,
colesterol-HDL, trigliceridos y colesterol no-HDL fueron del 9,73%, 12,5%, 1,9%,
3,15% y 13,2%, respectivamente. Se obtuvieron diferencias estadisticamente
significativas entre el grupo experimental y el grupo control, para todos los
marcadores analizados excepto para los trigliceridos.Conclusion: los esteroles
vegetales suministrados en un alimento de consumo habitual, como la leche, pueden
ser una estrategia terapeutica no farmacologica para el control de la
hipercolesterolemia de alto interes sanitario.
PMID- 27513507
TI - [Not Available].
AB - OBJECTIVE: The present study aims to compare the vertical counts registered by
GT1M, GT3X and ActiTrainer. METHODS: Treadmill activities, repeated sit-stands
and rest were completed by 31 young, 31 adults and 35 older adults while wearing
the accelerometers (GT1M, GT3X and ActiTrainer) on their right hips. Independent
sample t-test analyses were performed to determine differences between counts in
each age group and activities along with the Bland & Altman analysis to determine
the degree of agreement. In order to determine the correction factor for the
ActiTrainer counts, the linear regression forward analysis was used to minimize
differences with the GT3X and the GT1M counts. RESULTS: Differences among
ActiTrainer, GT1M, and GT3X were revealed in all activities except in rest. The
counts for ActiTrainer were significantly lower than those of GT3X and GT1M. The
correction factor for ActiTrainer with GT1M (GT1M counts = 3185.564 + 649.647;
*ActiTrainer counts - 36.163; *weight [kg] - 7.545 *age [years] r = 0.864; r2 =
0.746; r2 corrected = 0.745; SEE = 1451) and GT3X (GT3X counts = 3501.977 +
705.662 *ActiTrainer counts - 40.523 *weight [kg] - 11.864 *age [years] r =
0.901; r2 = 0.812; r2 corrected = 0.811; SEE = 310.160) reduced these
differences. CONCLUSION: The GT1M and GT3X vertical counts may be compared.
However, a correction factor to decrease differences to compare ActiTrainer
counts with those of GT1M or GT3X counts must be applied.
PMID- 27513508
TI - [Not Available].
AB - The endangered causes of Taxus chinensis var. maireiin the Taihang Mountains are
analyzed in three sides in connection with the situation that is resources
increasing attenuation.The first is biological factors such as pollination
barriers, deeply dormancy seed, cannot vegetative propagation under natural
conditions, poor adaptability of seedling to environment and slow growth. The
second is environmental factors such as very limited distribution environment and
position in community. The third is interference of persons and other
animals.According to these factors, we provide three measures to protect Taxus
chinensis var. maireiin three sides that protect existing resources, breed
subsequent resources and find new pathway of producing taxol.
PMID- 27513509
TI - [Not Available].
AB - OBJECTIVES: The association between fish consumption and the risk of breast
cancer has not been established yet. Results from epidemiological studies are
inconsistent. We conducted a meta-analysis to examine the association between
fish consumption and the risk of breast cancer. METHODS: We identified eligible
studies in Medline and EMBASE up to February 2015 and the reference lists of
original studies and review articles on this topic. Summary relative risks with
their 95% confidence intervals were calculated with a random-effects model.
RESULTS: We identified 27 studies eligible for analysis. The summary relative
risk of breast cancer for the highest consumption of fish compared with the
lowest was 0.96 (95% CI = 0.87-1.07), with evidence of heterogeneity (Q = 69.09,
p < 0.001, I2 = 68.0%). Four studies investigated lean fish consumption and
revealed that there was a small increase in the risk of breast cancer (summary RR
= 1.09, 95% CI = 1.00-1.19). As only four studies were included in the subgroup
analysis, results must be interpreted with caution. CONCLUSIONS: The overall
current literature on fish consumption and the risk of breast cancer suggested no
association. Further well-designed prospective studies are needed to explore fish
consumption in relation to breast cancer risk.
PMID- 27513510
TI - [Not Available].
AB - Objetivo: analizar la concordancia de dos metodos de medicion (Google MapsTM vs.
Sistema de Informacion Geografica) para la determinacion de la distancia desde el
domicilio familiar hasta el colegio.Metodos: un total de 542 escolares de entre 8
11 anos de edad (media = 9,36 +/- 0,6) del sur de Espana participaron en el
estudio, facilitando la direccion de su domicilio familiar. La distancia desde el
domicilio familiar al colegio se calculo mediante la utilizacion de dos programas
diferentes:Google MapsTM y Sistema de Informacion Geografica (GIS) en ruta y en
linea recta. La asociacion entre ambos metodos fue analizada utilizando la
correlacion de Spearman y el grado de acuerdo a traves del coeficiente de
correlacion intraclase (ICC), asi como el metodo Bland Altman.Resultados: la
correlacion entre ambos metodos de medicion propuestos fue muy significativa (r =
0,966, p < 0,001; r = 0,984, p < 0,001; y r = 0,954, p < 0,001, respectivamente),
y la concordancia fue excelente (ICC = 0,96, p < 0,001; ICC = 0,92, p < 0,001;
ICC = 0,97, p < 0,001).Conclusiones: los metodos de medicion estudiados podrian
ser utilizados en funcion de las necesidades de la investigacion, al presentar
ambos una alta concordancia. Sin embargo, se recomienda la utilizacion del
Sistema de Informacion Geografica en ruta si se cuenta con medios yfinanciacion,
por tratarse de un metodo constatado en fiabilidad y validez.
PMID- 27513511
TI - [Not Available].
AB - La fuerza influye directamente en el estado de salud y en la capacidad de
fitness, motivo por el que el entrenamiento contra resistencias o resistance
training (RT) se incluye dentro de aquellos programas de ejercicio encaminados a
mejorar la salud y calidad de vida. Debido a que muchasenfermedades cursan con
alteracion de la masa y funcionalidad muscular y a que el RT es la principal
modalidad de ejercicio encaminada a mejorar la funcion muscular, el objetivo de
la presente revision bibliografica ha sido exponer las evidencias actuales sobre
las adaptaciones delRT, asi como su posible aplicacion en patologias como la
obesidad, diabetes, dislipemia, hipertension, cancer, Parkinson, esclerosis
multiple o fibromialgia. El RT en estas enfermedades puede aumentar los niveles
de masa muscular, disminuyendo los niveles de masa grasa, los nivelesde acidos
grasos en sangre y la glucemia, incrementando la sensibilidad a la insulina, y
disminuyendo los niveles de citokinas inflamatorias. El RT, ademas, mejora el
gasto cardiaco y la funcionalidad endotelial, regulando la tension arterial e
incrementando el consumo de oxigeno. Las ganancias de fuerza muscular mejoran la
funcionalidad y la calidad de vida, especialmente en poblacion con una afectacion
neuromuscular grave, como pudieran ser los enfermos de esclerosis multiple,
fibromialgia o Parkinson. Por ello, el RT debe ser incorporado como parte del
tratamiento en las personas que presentan determinado tipo de patologias.
PMID- 27513512
TI - [Not Available].
AB - El indice de masa corporal (IMC) otorga uno de los indices mas usados para
determinar el estado nutricional de la poblacion a nivel mundial, donde a pesar
de existir recomendaciones claras y definidas para su interpretacion como el
sexo, edad, raza, entre otros, normalmente se estandariza su clasificacion,
independiente de las variables, aumentando el error en el resultado y en la
clasificacion del estado nutricional.El uso de la composicion corporal a traves
de la antropometria entrega mayor informacion que el IMC, siendo la masa grasa y
la masa muscular los principales resultados utiles.Este articulo presenta una
revision de las ecuaciones existentes y propone aquellas mas simples y con menor
error de estimacion para ser usadas como una herramienta que reemplace o
complemente al IMC, favoreciendo una mejor comprension e interpretacion del
estado nutricional y nivelde actividad fisica en ninos y adolescentes.
PMID- 27513513
TI - [Not Available].
AB - Introduccion: la disfagia es un sintoma que se refiere a la dificultad para mover
el bolo alimentario desde la boca al estomago. A pesar de su relevancia y de la
gravedad de sus posibles complicaciones, es poco conocida y estudiada. La
prevalencia de la disfagia orofaringea en enfermosde alzheimer es de un 84% y
puede originar complicaciones de gran trascendencia clinica como consecuencia de
las alteraciones en la eficacia de la deglucion, y en la seguridad de la
misma.Objetivo: conocer el estado actual del conocimiento en relacion al abordaje
de la disfagia en enfermos de alzheimer, localizando aquellos factores que
permitan un diagnostico precoz que facilite la prevencion de complicaciones y la
eleccion de la pauta de actuacion mas adecuada.Metodologia: revision sistematica.
Estudios publicados entre 2005 y 2014 en ingles y castellano. Bases de datos:
PubMed, Cochrane, Scopus, Elsevier, Scielo y Dialnet. Terminos MeSH empleados:
disfagia, dysphagia, alzheimer, modified y texture food.Resultados: el
diagnostico en los pacientes de alzheimer se realiza mediante metodos clinicos y
exploraciones complementarias como la videofluoroscopia, considerada como el
estandar para el estudio de la disfagia orofaringea, ya que permite identificar
entre 1/3 y 1/4 de los pacientes que presentan aspiraciones silentes no
diagnosticables clinicamente. Existen estrategias terapeuticas que incluyen
cambios en el volumen y viscosidad del bolo, cambios posturales, maniobras
deglutorias, procedimientos de rehabilitacion y tecnicas de incremento sensorial
que han demostrado su eficacia, pero se trata de una labor compleja que exige un
abordaje multidisciplinar para un correctodiagnostico y tratamiento.Conclusiones:
existe una escasa evidencia cientifica en el abordaje de la disfagia y un gran
desconocimiento en cuanto a la alimentacion de los enfermos de alzheimer. Esta
patologia necesita una intervencion multidisciplinar en la cual las medidas
dieteticas desempenan un papel primordial.
PMID- 27513514
TI - [Not Available].
AB - Objetivos: dar a conocer las recomendaciones relacionadas con la Nutricion Humana
y Dietetica (NHyD) de la Guia de Practica Clinica para el manejo de la enfermedad
de Parkinson del Sistema Nacional de Salud (GPC-EP/SNS) y favorecer su difusion e
implementacion en la practica. El objetivo secundario es presentar la implicacion
de los profesionales de la NHyD en la elaboracion de la guia.Material y metodos:
siguiendo el Manual Metodologico de Elaboracion de Guias de Practica Clinica en
el Sistema Nacional de Salud, se formularon las preguntas clinicas, se realizo
una busqueda sistematica para cada pregunta en bases de datos (PubMed/Medline,
Embase, Cochrane Library, CRD, LILACS, IBECS y ClinicalTrials), se definieron los
criterios de elegibilidad, al menos dos investigadores seleccionaron los
estudios, se realizo lectura critica de la literatura se resumio en tablas de
sintesis de evidencia y se establecieron las recomendaciones.Resultados: se
propusieron 14 preguntas relacionadas directamente con NHyD-Parkinson, de las
cuales solamente 3 pudieron incluirse. Se formulo una pregunta relacionada con la
terapia de logopedia aplicada en personas con EP que presentan problemas de
deglucion, tratamiento donde se imbrican los profesionales de la NHyD. De 642
articulos localizados, unicamente 2 pudieron ser incluidos para contestar las
correspondientes preguntas. De las evidencias halladas, se derivaron 11
recomendaciones directa o indirectamente relacionados con la NHyD.Conclusiones:
la implicacion de profesionales sanitarios en equipos multidisciplinares mejora
el resultado final de las guias y la atencion sanitaria de los pacientes. Es
necesario que los profesionales sanitarios de la NHyD (los/las dietistas
nutricionistas) se impliquen en iniciativas basadas en la mejor evidencia
cientifica disponible y que formen parte de los equipos de trabajo
multidisciplinares.
PMID- 27513515
TI - Dance participation and academic performance in youth girls
AB - Dance is a predominant type of physical activity among girls. Dance
characteristics imply skills associated to health-related physical fitness, as
well as others such as learning and memory, mental representation, imagination
and creativity, which are related to cognitive development. Although dance has
been shown to influence physical health among youth girls, whether dance may
influence academic performance and cognition in youth remains to be elucidated.
The objective of this work was to examine the association between participation
in dance and academic performance in youth girls.
PMID- 27513516
TI - Antibody to CMRF35-Like Molecule 2, CD300e A Novel Biomarker Detected in Patients
with Fulminant Type 1 Diabetes.
AB - AIMS/HYPOTHESIS: Fulminant type 1 diabetes (FT1D) is a distinct subtype of type 1
diabetes and is fatal without immediate diagnosis and treatment. At present,
there are no biomarkers for early and predictive detection of FT1D. METHODS:
First, we analyzed a total of 6 serum samples from 3 patients with FT1D (1 sample
in the acute and 1 in the sub-acute phases from each patient) by seromic
analysis. Second, titres of the antibody were measured by ELISA in sera from 30
patients with FT1D (both in the acute and sub-acute phases), 13 patients with
FT1D in the chronic phase, 32 patients with autoimmune type 1 (type 1A) diabetes
(T1AD), 30 patients with type 2 diabetes (T2D), 23 patients with autoimmune
thyroid disease (AITD) and 31 healthy control subjects (HC). RESULTS: Seromic
analysis revealed 9 antibodies which showed high signals from all 3 patients with
FT1D in the acute phase. Among them, the titre of anti-CD300e antibody was
significantly higher in FT1D patients in the acute phase than that in T1AD, T2D,
AITD patients and HC, as determined by ELISA (P<0.01, respectively). The titre of
anti-CD300e antibody was also higher in FT1D in the acute phase than that in the
sub-acute phase (P = 0.0018, Wilcoxon signed-rank test). The titre of anti-LGALS3
antibody in FT1D patients in the acute phase did not differ from that in patients
with FT1D in the sub-acute phase, T1AD, T2D, AITD and HC.
CONCLUSION/INTERPRETATION: The titre of a novel antibody, anti-CD300e, was high
in sera from patients with FT1D. This antibody might be a diagnostic marker and
provide new insight into the pathogenesis of FT1D.
PMID- 27513517
TI - Association of FMO3 Variants and Trimethylamine N-Oxide Concentration, Disease
Progression, and Mortality in CKD Patients.
AB - Elevated levels of circulating pro-atherogenic uremic solutes, particularly
trimethylamine N-oxide (TMAO), have been implicated in cardiovascular disease
development in patients with chronic kidney disease (CKD). TMAO is generated from
trimethylamine (TMA) via metabolism by hepatic flavin-containing monooxygenase
isoform 3 (FMO3). We determined the functional effects of three common FMO3
variants at amino acids 158, 308, and 257 on TMAO concentrations in a prospective
cohort study and evaluated associations of polymorphisms with CKD progression and
mortality. Each additional minor allele at amino acid 158 was associated with a
0.38 MUg/mL higher circulating TMAO (p = 0.01) and with faster rates of
annualized relative eGFR decline. Participants with 0, 1 and 2 variant alleles
averaged an eGFR loss of 8%, 12%, and 14% per year, respectively (p-for trend =
0.05). Compared to participants with the homozygous reference allele,
heterozygous and homozygous variant participants had a 2.0-fold (95% CI: 0.85,
4.6) and 2.2-fold (95% CI: 0.89, 5.48) higher risk of mortality, respectively (p
for-trend = 0.04). No associations with clinical outcomes were observed for
allelic variants at amino acids 257 or 308. Understanding the contribution of
genetic variation of FMO3 to disease progression and all-cause mortality can
guide recommendations for diet modification or pharmacotherapy in CKD patients at
increased risk of adverse outcomes.
PMID- 27513518
TI - Tumor-Specific Peptide, Selected from a Phage Peptide Library, Enhances Antitumor
Activity of Lactaptin.
AB - A recombinant analogue of lactaptin (RL2), a new potential anticancer molecule,
induces apoptosis in cultured tumor cells. The tumor suppression efficacy of RL2
was shown against mouse hepatoma-1 cells and MDA-MB-231 human breast
adenocarcinoma cells. The RL2-based therapeutic drug lactaptin is distributed
evenly throughout the organism, which reduces its antitumor efficacy. In the
current study, we obtained a genetic construct that allows production of the
recombinant fusion protein T3-RL2, consisting of RL2 and T3 peptide
(YTYDPWLIFPAN), in E. coli cells. T3 peptide was selected from a phage peptide
library as a result of two screenings: in vitro using MDA-MB-231 cell culture and
in vivo using a mouse xenograft model of breast cancer MDA-MB-231. It was shown
that the displayed peptide T3 provides binding and internalization of phage
particles by MDA-MB-231 cells and their specific accumulation in MDA-MB-231 tumor
tissue. In addition, based on the nucleotide sequences coding RL2 and the known
tumor-targeting peptide iRGD, we obtained genetic constructs that provide
synthesis of fusion proteins RL2-iRGD and RL-iRGD-His. We studied the cytotoxic
activity of fusion proteins T3-RL2, RL2-iRGD and RL-iRGD-His in vitro using MDA
MB-231 and MCF-7 human adenocarcinoma cells. The in vitro results showed that the
fusion proteins inhibit proliferation of both cell cultures, and their cytotoxic
activity is higher than that of RL2. In vivo experiments on the study of the
antitumor efficacy of the obtained fusion proteins demonstrated that T3-RL2
protein significantly inhibits MDA-MB-231 tumor growth in a xenograft model
compared with RL2, while the antitumor effect of RL2-iRGD and RL-iRGD-His
proteins is comparable to the effect of RL2.
PMID- 27513519
TI - Correlating optic nerve sheath diameter with opening intracranial pressure in
pediatric traumatic brain injury.
AB - INTRODUCTION: The use of clinical markers to predict intracranial pressure (ICP)
is desirable as a first-line measure to assist in decision making as to whether
invasive monitoring is required. Correlations between ICP and optic nerve sheath
diameter (ONSD) using CT and MRI have been observed in adult populations.
However, data on this modality in children is less well documented. METHODS: ONSD
was measured by independent observers and correlated with opening ICP at
insertion of invasive monitoring probes in pediatric traumatic brain injury
patients admitted to Addenbrookes Hospital between January 2009 and December
2013. RESULTS: Thirty-six patients with a mean age of 8.2 y were admitted to the
Pediatric Intensive Care Unit (PICU) with a traumatic head injury and required
invasive neurosurgical monitoring. The median ICP was 18 +/- 10 mmHg (median +/-
IQR), the median right ONSD was 5.6 +/- 2.5 mm and the left was 5.9 +/- 3.2 mm.
The Intraclass correlation between observers was 0.91 (P < 0.0001). The
correlation of mean ONSD and max ONSD with ICP was 0.712 (P < 0.0001) and 0.713
(P < 0.0001), respectively. Area under ROC curve for both mean and max ONSD is
0.85 (95% CI: 0.73-0.98). CONCLUSION: Where pediatric patients present with an
ONSD of over 6.1 mm following a traumatic brain injury (TBI), ICP monitoring
should be implemented.
PMID- 27513520
TI - Effects of Venous Superdrainage and Arterial Supercharging on Dorsal Perforator
Flap in a Rat Model.
AB - OBJECTIVE: To comparatively assess the effects of venous superdrainage and
arterial supercharging on dorsal perforator flap survival. MATERIALS AND METHODS:
Sixty male Sprague-Dawley rats (450-550g) were randomly divided into three groups
(n = 20), including control group (Control) and experimental groups A (venous
superdrainage, Exp. A) and B (arterial supercharging, Exp. B). At postoperative
day 7, survival areas of the flaps were evaluated and all animals underwent
angiography. Laser Doppler was used to evaluate flap perfusion from 0h to 7days
after surgery. Histology with hematoxylin and eosin staining was used to count
microvessels. Tissue of "Choke vessels"was excised for quantification of hypoxia
inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor
(VEGF) by western blot assay at 6h and 7days after surgery. RESULTS: In the Exp.
A group, almost all flaps survived (98.2+/-1.6%); in the Exp. B and control
group, survival areas accounted for 78.8+/-8.5% and 60.3+/-7.8%, respectively (P
<0.001). In addition, Exp. A animals showed improved anastomosis of choke vessels
2 compared with the Exp. B and Control groups. Furthermore, flap blood flow and
partial pressure of oxygen in the Exp. A group were significantly higher compared
with values obtained for the Exp. B and Control groups, from 6 hours to 7 days
after surgery. More microvessels were found in the Exp. A group (11.65+/-1.33)
than in Exp. B (9.25+/-0.34) and control (7.25+/-0.91) animals on POD 7. The
relative expression level of HIF-1alpha and VEGF were significant at 6h and 7days
after surgery. CONCLUSIONS: Venous superdrainage in rat dorsal perforator flap is
more effective than arterial supercharging in promoting flap survival, and could
effectively alter hemodynamics in the microcirculation and stimulate blood vessel
formation.
PMID- 27513521
TI - Impact of enumeration method on diversity of Escherichia coli genotypes isolated
from surface water.
AB - : There are numerous regulatory-approved Escherichia coli enumeration methods,
but it is not known whether differences in media composition and incubation
conditions impact the diversity of E. coli populations detected by these methods.
A study was conducted to determine if three standard water quality assessments,
Colilert(r) , USEPA Method 1603, (modified mTEC) and USEPA Method 1604 (MI),
detect different populations of E. coli. Samples were collected from six
watersheds and analysed using the three enumeration approaches followed by E.
coli isolation and genotyping. Results indicated that the three methods generally
produced similar enumeration data across the sites, although there were some
differences on a site-by-site basis. The Colilert(r) method consistently
generated the least diverse collection of E. coli genotypes as compared to
modified mTEC and MI, with those two methods being roughly equal to each other.
Although the three media assessed in this study were designed to enumerate E.
coli, the differences in the media composition, incubation temperature, and
growth platform appear to have a strong selective influence on the populations of
E. coli isolated. This study suggests that standardized methods of enumeration
and isolation may be warranted if researchers intend to obtain individual E. coli
isolates for further characterization. SIGNIFICANCE AND IMPACT OF THE STUDY: This
study characterized the impact of three USEPA-approved Escherichia coli
enumeration methods on observed E. coli population diversity in surface water
samples. Results indicated that these methods produced similar E. coli
enumeration data but were more variable in the diversity of E. coli genotypes
observed. Although the three methods enumerate the same species, differences in
media composition, growth platform, and incubation temperature likely contribute
to the selection of different cultivable populations of E. coli, and thus caution
should be used when implementing these methods interchangeably for downstream
applications which require cultivated isolates.
PMID- 27513523
TI - Notes from the Field: Shigellosis Outbreak Among Men Who Have Sex with Men and
Homeless Persons - Oregon, 2015-2016.
AB - In July 2015, Shigella sonnei infections with a specific pulsed-field gel
electrophoresis (PFGE) pattern linked to a multistate outbreak were recognized
among men who have sex with men (MSM) in the Portland metropolitan area, and an
outbreak investigation was initiated. During November 2015, isolates with PFGE
patterns indistinguishable from the outbreak strain were identified in cases
reported in four women, none of whom had epidemiologic links to other affected
persons; however, three reported homelessness. In the ensuing months, additional
S. sonnei infections were reported among homeless persons in the Portland area.
PMID- 27513522
TI - West Nile virus-infected human dendritic cells fail to fully activate invariant
natural killer T cells.
AB - West Nile virus (WNV) infection is a mosquito-borne zoonosis with increasing
prevalence in the United States. WNV infection begins in the skin, and the virus
replicates initially in keratinocytes and dendritic cells (DCs). In the skin and
cutaneous lymph nodes, infected DCs are likely to interact with invariant natural
killer T cells (iNKTs). Bidirectional interactions between DCs and iNKTs amplify
the innate immune response to viral infections, thus controlling viral load and
regulating adaptive immunity. iNKTs are stimulated by CD1d-bound lipid antigens
or activated indirectly by inflammatory cytokines. We exposed human monocyte
derived DCs to WNV Kunjin and determined their ability to activate isolated blood
iNKTs. DCs became infected as judged by synthesis of viral mRNA and Envelope and
NS-1 proteins, but did not undergo significant apoptosis. Infected DCs up
regulated the co-stimulatory molecules CD86 and CD40, but showed decreased
expression of CD1d. WNV infection induced DC secretion of type I interferon
(IFN), but no or minimal interleukin (IL)-12, IL-23, IL-18 or IL-10.
Unexpectedly, we found that the WNV-infected DCs stimulated human iNKTs to up
regulate CD69 and produce low amounts of IL-10, but not proinflammatory cytokines
such as IFN-gamma or tumour necrosis factor (TNF)-alpha. Both CD1d and IFNAR
blockade partially abrogated this iNKT response, suggesting involvement of a T
cell receptor (TCR)-CD1d interaction and type I interferon receptor (IFNAR)
signalling. Thus, WNV infection interferes with DC-iNKT interactions by
preventing the production of proinflammatory cytokines. iNKTs may be a source of
IL-10 observed in human flavivirus infections and initiate an anti-inflammatory
innate response that limits adaptive immunity and immune pathology upon WNV
infection.
PMID- 27513524
TI - P2-Type Na0.67Ni0.23Mg0.1Mn0.67O2 as a High-Performance Cathode for a Sodium-Ion
Battery.
AB - There is intense interest in sodium-ion batteries as an alternative to lithium
ion batteries for electric storage applications because of the low-cost and
abundant sodium resources. Na0.67Ni0.33-xMgxMn0.67O2 compounds (x = 0, 0.02,
0.05, 0.1, or 0.15) were prepared by a sol-gel method and used as a cathode for
sodium-ion batteries. The X-ray powder diffraction measurements demonstrated that
the obtained samples have a pure P2 phase. Na0.67Ni0.23Mg0.1Mn0.67O2 delivers an
initial reversible capacity of 105 mAh g(-1) in the potential region from 2.0 to
4.5 V at a charge/discharge current density of 48 mA g(-1). Moreover, the
cyclability is improved by doping Mg. The capacity of Na0.67Ni0.23Mg0.1Mn0.67O2
can remain at approximately 84.9 mAh g(-1) at a current density of 48 mA g(-1)
after 100 cycles. The improved high rate performance of Na0.67Ni0.23Mg0.1Mn0.67O2
was attributed to the increased lattice parameters and d spacing of the Na(+)
layer. Therefore, Mg-doped Na0.67Ni0.23Mg0.1Mn0.67O2 is a promising cathode for
sodium-ion batteries with excellent rate and cyclic performance.
PMID- 27513526
TI - Decidual Vasculopathy: Placental Location and Association with Ischemic Lesions.
AB - Decidual vasculopathy (DV) is a general term for a number of lesions involving
uteroplacental vessels. It is often seen in preeclamptic placentas and indicates
a disorder of uteroplacental malperfusion and is associated with placental
ischemia and infarction. Although some have advocated submitting special sections
in order to better document DV, it is unclear which placental sections have the
highest yield in demonstrating these abnormal vessels. 76 consecutive cases of
decidual vasculopathy were identified and evaluated for location of DV, as well
as presence of other lesions of ischemic change, infarcts and retroplacental
hematomas. Sections reviewed were the membrane roll, full thickness sections of
the placental disc, and sections specifically of the basal plate. DV was found in
the membrane roll (MR) in 67.1% of cases, in full thickness sections (FT) in
32.9% and in the basal plate (BP) in 25.0% of cases (p value = 0.004). DV was
exclusive to the MR in 53.9%, the FT in 14.5% and the BP in 9.2%. DV was present
in 2 locations in 19.7% and in all 3 locations in 2.6%. The presence of DV in any
location (MR, FT, BP) was associated with placental ischemic change but not
specifically with infarcts or retroplacental hematomas. The specific location of
DV showed no difference in the presence of placental lesions. Our findings
indicate DV is often present in one location, and is associated with lesions of
malperfusion. It is recommended that when clinically indicated, additional
sections are submitted to demonstrate decidual vasculopathy.
PMID- 27513527
TI - Ingenol Mebutate for Lentigo Maligna: A Case Report.
AB - BACKGROUND: Lentigo maligna (LM) is a melanoma in situ on sun-damaged skin, with
a strong predilection to the head and neck area of the elderly. Many therapeutic
modalities have been proposed in the treatment of this pathology, including
surgery, cryotherapy, radiotherapy and topical imiquimod. Up to date surgical
excision remains the treatment of choice with the lowest recurrence rate.
Recently, a new topical treatment with ingenol mebutate has been described to be
efficacious and well tolerated in the treatment of melanoma in situ. OBJECTIVE:
We sought to demonstrate that ingenol mebutate might be an efficacious and well
tolerated treatment in a patient suffering from LM on an aesthetically
challenging location. METHODS: Case report. RESULTS: After therapeutic failure
with imiquimod 5% cream, a new topical treatment with ingenol mebutate gel 0.015%
once daily on 3 consecutive days was initiated. Despite visible inflammation, no
macroscopic lesion clearance was observed. While the first follow-up using
reflectance confocal microscopy (RCM) performed at 6 weeks after the completion
of the therapy showed no signs of LM, the second follow-up examination at 12
weeks using RCM and biopsy confirmed recurrence of the lesion. CONCLUSION:
Ingenol mebutate cannot be considered a standard treatment modality for all types
of LM. Further studies are needed to evaluate the prerequisites that can ensure
therapeutic success.
PMID- 27513528
TI - Group Cognitive Behaviour Therapy for Chronic Fatigue Syndrome.
PMID- 27513529
TI - MCPIP-1, Alias Regnase-1, Controls Epithelial Inflammation by Posttranscriptional
Regulation of IL-8 Production.
AB - Pattern recognition receptors are critical for the detection of invading
microorganisms. They activate multiple pathways that lead to the induction of
proinflammatory responses and pathogen clearance. The intensity and duration of
this immune reaction must be tightly controlled spatially and temporally in every
tissue by different negative regulators. We hypothesized that monocyte
chemoattractant protein-1-induced protein-1 (MCPIP-1) might play a role in
maintaining immune homeostasis in the epithelium both under physiological
conditions and upon bacterial infection. To this end, we examined the
distribution of the MCPIP-1 transcript and protein in various tissues. The MCPIP
1 protein level was higher in epithelial cells than in myeloid cells. MCPIP-1
exerted RNase activity towards the interleukin (IL)-8 transcript and the lifespan
of IL-8 was determined by the presence of the stem-loops/hairpin structures at
the 3'UTR region of IL-8 mRNA. Moreover, using fully active, purified recombinant
MCPIP-1 protein, we elucidated the mechanism by which MCPIP-1 controls the IL-8
mRNA level. In conclusion, we uncovered a novel IL-8-dependent mechanism via
which MCPIP-1 maintains epithelial homeostasis. This study reveals for the first
time that MCPIP-1 plays a crucial anti-inflammatory role not only in myeloid
cells but also in epithelial cells.
PMID- 27513530
TI - Microbial investigation of biofilms recovered from endotracheal tubes using
sonication in intensive care unit pediatric patients.
AB - OBJECTIVES: To compare cultured microorganisms identified on endotracheal tubes
biofilms through sonication technique with traditional tracheal aspirate
collected at extubation of pediatric intensive care unit patients. METHODS:
Demographic and epidemiological data were analyzed to identify factors possibly
related with the microbiological profile of the two collection methods.
Associations between categorical and continuous variables were analyzed using the
chi-square or Fisher's exact test, or Student's t test. p-Value <0.05 were
considered significant. RESULTS: Thirty endotracheal tubes and tracheal aspirates
samples from 27 subjects were analyzed. Only one patient presented the clinical
diagnosis of ventilator-associated pneumonia. Overall, 50% of bacteria were Gram
negative bacilli, followed by Gram-positive bacteria in 37%, and fungi in 10%. No
statistically significant difference on the distribution of Gram-positive or Gram
negative bacteria (p=0.996), and fungi (p=0.985) were observed between the
collection methods. Pseudomonas spp. was the most frequent microorganism
identified (23.8%), followed by Streptococcus spp. (18.5%), Acinetobacter spp.
(15.9%), coagulase-negative staphylococci (11.2%), and Klebsiella spp. (8.6%).
Concordant results between methods amounted to 83.3%. Pseudomonas aeruginosa and
Acinetobacter baumannii showed carbapenem resistance in 50% and 43.7% of the
isolates, respectively. In general, cultures after endotracheal tubes sonication
(non-centrifuged sonication fluid and centrifuged sonication fluid) yielded
bacteria with higher rates of antimicrobial resistance compared to tracheal
aspirates cultures. Additionally, in 12 subjects (40%), we observed discrepancies
regarding microbiologic profiles of cultures performed using the collection
methods. CONCLUSIONS: Our study demonstrated that sonication technique can be
applied to ET biofilms to identify microorganisms attached to their surface with
a great variety of species identified. However, we did not find significant
differences in comparison with the traditional tracheal aspirate culture
approach.
PMID- 27513531
TI - Assessment of an intervention aimed at early discontinuation of intravenous
antimicrobial therapy in a Brazilian University hospital.
AB - Many interventions demonstrate success in adapting the duration of intravenous
antibiotic therapy, but few studies have been conducted in developing countries.
The aim of this study was to evaluate the effectiveness of an intervention in the
induction of early discontinuation of intravenous antimicrobial therapy and/or
its switch to oral therapy. The study employed a before-after intervention design
that consisted of displaying a message in the computerized prescription on the
third day and suspension of the prescription on the fifth day of intravenous
antimicrobial therapy. A total of 465 patients were followed during the control
period (CP) and 440 in the intervention period (IP). The intravenous therapy was
switched to oral therapy for 11 (2.4%) patients during the CP and 25 (5.7%) in
the IP (p=0.011), and was discontinued for 82 (17.6%) patients during the CP and
106 (24.1%) in the IP (p=0.017). During the IP there was a significant increase
of patients who had their antimicrobial treatment discontinued before the seventh
day of intravenous treatment, 37.40% (49/131) in the IP and 16.13% (15/93) in the
CP (p=0.0005). The duration of intravenous antimicrobial therapy decreased by one
day, but it was not significant (p=0.136). It is concluded that the proposed
intervention is effective in promoting the early discontinuation of antimicrobial
treatment and/or switch to oral therapy. As long as a computerized system for
prescription already exists, it is easy and inexpensive to be implemented,
especially in hospitals in developing countries.
PMID- 27513532
TI - Patient, Process, and System Predictors of Iatrogenic Withdrawal Syndrome in
Critically Ill Children.
AB - OBJECTIVE: To generate a multidimensional predictive model of risk factors for
iatrogenic withdrawal syndrome in critically ill children. DESIGN: Secondary
analysis of prospective data from the Randomized Evaluation of Sedation Titration
for Respiratory Failure clinical trial. SETTING: PICU. PATIENTS: Children who
received greater than or equal to 5 days of sedation during mechanical
ventilation for acute respiratory failure. INTERVENTIONS: The Randomized
Evaluation of Sedation Titration for Respiratory Failure study tested the effect
of a nurse-led, goal-directed sedation protocol on clinical outcomes. There was
no additional intervention in this secondary analysis. MEASUREMENTS AND MAIN
RESULTS: Data included 1,157 children from 31 PICUs. Iatrogenic withdrawal
syndrome was defined as having at least two Withdrawal Assessment Tool-Version 1
scores greater than or equal to 3 after the start of opioid weaning. Logistic
regression with generalized estimating equations to account for clustering by
site was used to evaluate patient, process, and healthcare system risk factors
for iatrogenic withdrawal syndrome. Subjects with iatrogenic withdrawal syndrome
(544/1,157; 47%) were younger and more likely to have preexisting cognitive or
functional impairment. They also received higher sedative doses and longer
exposure periods. In multivariable analyses, significant predictors of iatrogenic
withdrawal syndrome included younger age, preexisting cognitive impairment,
higher preweaning mean daily opioid dose, longer duration of sedation, receipt of
three or more preweaning sedative classes, higher nursing workload, and more one
to-one nurse staffing. CONCLUSIONS: Iatrogenic withdrawal syndrome is common in
children recovering from critical illness, and several risk factors are
predictive, including patient characteristics, sedative exposure, additional
sedative agents, and system-level factors. High-risk patients could be identified
before weaning to better prevent iatrogenic withdrawal syndrome among at-risk
patients.
PMID- 27513533
TI - Overtreatment of Heparin-Induced Thrombocytopenia in the Surgical ICU.
AB - OBJECTIVE: Recent studies reveal a high occurrence of overdiagnosis of heparin
induced thrombocytopenia in surgical patients with critical illness. The optimal
criteria for diagnosis of heparin-induced thrombocytopenia remain unclear,
contributing to unnecessary treatment. We reviewed patients who were admitted to
surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify
how often patients were correctly treated. DESIGN: In this clinical prospective
study, data were collected including age, sex, antiplatelet factor 4/heparin
enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts
scores. Heparin-induced thrombocytopenia-positive patients were defined as those
with both positive antiplatelet factor 4/heparin enzyme-linked immunosorbent
assay (optical density, >= 0.40) and positive serotonin release assay results.
SETTING: Urban tertiary medical center. PATIENTS: Patients admitted to the
surgical and cardiac ICU who were presumed to have heparin-induced
thrombocytopenia and underwent antiplatelet factor 4/heparin enzyme-linked
immunosorbent assay and serotonin release assay testing between January 1, 2011,
and August 1, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total
of 135 patients had 4Ts, antiplatelet factor 4/heparin enzyme-linked
immunosorbent assay, and serotonin release assay scores. A total of 11 patients
(8.1%) had positive serotonin release assay and 80 patients had positive
antiplatelet factor 4/heparin enzyme-linked immunosorbent assay; 10 patients were
identified as heparin-induced thrombocytopenia positive. Positive serotonin
release assay was noted in nine of 11 patients (81.8%) with antiplatelet factor
4/heparin enzyme-linked immunosorbent assay optical density greater than or equal
to 2.0, compared with one of 22 patients (4.5%) with optical density values of
0.85-1.99, and one of 102 patients (1.0%) with optical density values of 0-0.84.
Out of 135 patients, 29 patients (21.5%) received treatment with argatroban,
lepirudin, or fondaparinux: 10 of 10 heparin-induced thrombocytopenia-positive
patients (100%) compared with 19 of 125 heparin-induced thrombocytopenia-negative
patients (15%). CONCLUSIONS: Overtreatment of heparin-induced thrombocytopenia in
the surgical ICU continues even with recent increased caution encouraging a
higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical
density threshold before initiating treatment. More stringent criteria should be
used to determine when to order serologic testing and when the results of such
testing should prompt a change in anticoagulant treatment. If antiplatelet factor
4/heparin enzyme-linked immunosorbent assay is used to consider immediate
treatment, an optical density greater than or equal to 2.0 may be a more
appropriate threshold.
PMID- 27513534
TI - Atrial Fibrillation Following Out-of-Hospital Cardiac Arrest and Targeted
Temperature Management-Are We Giving It the Attention it Deserves?
AB - OBJECTIVES: Atrial fibrillation has been associated with increased mortality in
the general population and mixed populations of critical ill. Atrial fibrillation
can also affect patients during post-cardiac arrest care. We sought to assess the
prognostic implications of atrial fibrillation following out-of-hospital cardiac
arrest, including relation to the level of targeted temperature management.
DESIGN: A post hoc analysis of a prospective randomized trial. SETTING: Thirty
six ICUs. PATIENTS: We included 897 (96%) of the 939 comatose out-of-hospital
cardiac arrest survivors from the targeted temperature management trial (year,
2010-2013) with data on heart rhythm on day 2. INTERVENTIONS: Targeted
temperature management at 33 degrees C or 36 degrees C. MEASUREMENTS AND MAIN
RESULTS: Endpoints included cumulative proportion of atrial fibrillation
following out-of-hospital cardiac arrest and 180-day all-cause mortality and
specific death causes stratified by atrial fibrillation. Atrial fibrillation on
day 2 was used as primary endpoint analyses to exclude effects of short-term
atrial fibrillation related to resuscitation and initial management. The
cumulative proportions of atrial fibrillation were 15% and 11% on days 1 and 2,
respectively. Forty-three percent of patients with initial atrial fibrillation
the first day were reported with sinus rhythm on day 2. No difference was found
between the groups treated with targeted temperature management at 33 degrees C
and 36 degrees C. Patients affected by atrial fibrillation had significantly
higher 180-day mortality (atrial fibrillation: 66% vs no-atrial fibrillation:
43%; plogrank < 0.0001 and unadjusted hazard ratio, 1.75 [1.35-2.30]; p <
0.0001). The association between atrial fibrillation and higher mortality
remained significant (adjusted hazard ratio, 1.34 [1.01-1.79]; p < 0.05) adjusted
for potential confounders. Atrial fibrillation was independently associated with
increased risk of cardiovascular death and multiple-organ failure (adjusted
hazard ratio, 2.07 [1.39-3.09]; p < 0.001), whereas no association with higher
risk of death from cerebral causes was found. CONCLUSIONS: Atrial fibrillation
was independently associated with higher mortality, primarily driven by
cardiovascular causes and multiple-organ failure, and may thus identify a
vulnerable subpopulation. Whether treatment to prevent atrial fibrillation is
associated with an improved prognosis remains to be established.
PMID- 27513535
TI - Association of Freestanding Children's Hospitals With Outcomes in Children With
Critical Illness.
AB - OBJECTIVES: Little is known about the relationship between freestanding
children's hospitals and outcomes in children with critical illness. The purpose
of this study was to evaluate the association of freestanding children's
hospitals with outcomes in children with critical illness. DESIGN: Propensity
score matching was performed to adjust for potential confounding variables
between patients cared for in freestanding or nonfreestanding children's
hospitals. We tested the sensitivity of our findings by repeating the primary
analyses using inverse probability of treatment weighting method and regression
adjustment using the propensity score. SETTING: Retrospective study from an
existing national database, Virtual PICU Systems (LLC) database. PATIENTS:
Patients less than 18 years old admitted to one of the participating PICUs in the
Virtual PICU Systems, LLC database were included (2009-2014). INTERVENTIONS:
None. MEASUREMENTS AND MAIN RESULTS: A total of 538,967 patients from 140 centers
were included. Of these, 323,319 patients were treated in 60 freestanding
hospitals. In contrast, 215,648 patients were cared for in 80 nonfreestanding
hospitals. By propensity matching, 134,656 patients were matched 1:1 in the two
groups (67,328 in each group). Prior to matching, patients in the freestanding
hospitals were younger, had greater comorbidities, had higher severity of illness
scores, had higher incidence of cardiac arrest, had higher resource utilization,
and had higher proportion of patients undergoing complex procedures such as
cardiac surgery. Before matching, the outcomes including mortality were worse
among the patients cared for in the freestanding hospitals (freestanding vs
nonfreestanding, 2.5% vs 2.3%; p < 0.001). After matching, the majority of the
study outcomes were better in freestanding hospitals (freestanding vs
nonfreestanding, mortality: 2.1% vs 2.8%, p < 0.001; standardized mortality
ratio: 0.77 [0.73-0.82] vs 0.99 [0.87-0.96], p < 0.001; reintubation: 3.4% vs
3.8%, p < 0.001; good neurologic outcome: 97.7% vs 97.1%, p = 0.001).
CONCLUSIONS: In this large observational study, we demonstrated that ICU care
provided in freestanding children's hospitals is associated with improved risk
adjusted survival chances compared to nonfreestanding children's hospitals.
However, the clinical significance of this change in mortality should be
interpreted with caution. It is also possible that the hospital structure may be
a surrogate of other factors that may bias the results.
PMID- 27513536
TI - Mindfulness and Coping Are Inversely Related to Psychiatric Symptoms in Patients
and Informal Caregivers in the Neuroscience ICU: Implications for Clinical Care.
AB - OBJECTIVE: To assess the correlation of psychosocial resiliency factors
(mindfulness and coping) with symptoms of posttraumatic stress, anxiety, and
depression in patients recently admitted to the neuroscience ICU and their
primary informal caregivers. DESIGN: A descriptive, cross-sectional correlational
study. SETTING: Neuroscience ICU in a major medical center. PARTICIPANTS: A total
of 78 dyads of patients (total n = 81) and their primary caregivers (total n =
92) from June to December 2015. Study enrollment occurred within the first 2
weeks of patient admission to the neuroscience ICU. INTERVENTION: None.
MEASUREMENTS AND MAIN RESULTS: Dyads completed self-report measures of
mindfulness (Cognitive and Affective Mindfulness Scale-Revised), coping (Measure
of Coping Status-A), posttraumatic stress (Posttraumatic Checklist-Specific
Stressor), anxiety (Hospital Anxiety and Depression Scale-A), and depression
(Hospital Anxiety and Depression Scale-D). Rates of clinically significant
posttraumatic stress, anxiety, and depressive symptoms were high and comparable
between patient and caregiver samples. Own psychological resilience factors and
psychiatric symptoms were strongly correlated for both patients and caregivers.
Depressive symptoms were interdependent between patients and their caregivers,
and one's own mindfulness was independently related to one's partner's depressive
symptoms. CONCLUSIONS: Rates of clinically significant psychiatric symptoms were
high, equally prevalent in patients and caregivers, and interdependent between
patients and their caregivers. For both patients and caregivers, psychological
resiliency factors were associated with both self and partner psychiatric
symptoms. Findings suggest that attending to the psychiatric health of both
patients and caregivers in the neuroscience ICU is a priority and that patients
and their caregivers must be considered together in a system to fully address
either individual's psychiatric symptoms.
PMID- 27513537
TI - Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis
Biomarker Risk Model With Septic Shock Phenotype.
AB - OBJECTIVE: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric
sepsis risk model, uses biomarkers to estimate baseline mortality risk for
pediatric septic shock. It is unknown how PERSEVERE performs within distinct
septic shock phenotypes. We tested PERSEVERE in children with septic shock and
thrombocytopenia-associated multiple organ failure (TAMOF), and in those without
new onset thrombocytopenia but with multiple organ failure (MOF). DESIGN:
PERSEVERE-based mortality risk was generated for each study subject (n = 660). A
priori, we determined that if PERSEVERE did not perform well in both the TAMOF
and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet
counts. SETTING: Multiple PICUs in the United States. INTERVENTIONS: Standard
care. MEASUREMENTS AND MAIN RESULTS: PERSEVERE performed well in the TAMOF cohort
(areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI,
0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE
was revised using 424 subjects previously reported in the derivation phase.
PERSEVERE-II had an AUC of 0.89 (0.85-0.93) and performed equally well across
TAMOF and MOF cohorts. PERSEVERE-II performed well when tested in 236 newly
enrolled subjects. Sample size calculations for a clinical trial testing the
efficacy of plasma exchange for children with septic shock and TAMOF indicated
PERSEVERE-II-based stratification could substantially reduce the number of
patients necessary, when compared with no stratification. CONCLUSIONS: Testing
PERSEVERE in the context of septic shock phenotypes prompted a revision
incorporating platelet count. PERSEVERE-II performs well upon testing,
independent of TAMOF or MOF status. PERSEVERE-II could potentially serve as a
prognostic enrichment tool.
PMID- 27513538
TI - Computational Analysis Supports an Early, Type 17 Cell-Associated Divergence of
Blunt Trauma Survival and Mortality.
AB - OBJECTIVE: Blunt trauma patients may present with similar demographics and injury
severity yet differ with regard to survival. We hypothesized that this divergence
was due to different trajectories of systemic inflammation and utilized
computational analyses to define these differences. DESIGN: Retrospective
clinical study and experimental study in mice. SETTING: Level 1 trauma center and
experimental laboratory. PATIENTS: From a cohort of 493 victims of blunt trauma,
we conducted a pairwise, retrospective, case-control study of patients who
survived over 24 hours but ultimately died (nonsurvivors; n = 19) and patients
who, after ICU admission, went on to be discharged(survivors; n = 19).
INTERVENTIONS: None in patients. Neutralizing anti-interleukin-17A antibody in
mice. MEASUREMENTS AND MAIN RESULTS: Data on systemic inflammatory mediators
assessed within the first 24 hours and over 7 days were analyzed with
computational modeling to infer dynamic networks of inflammation. Network density
among inflammatory mediators in nonsurvivors increased in parallel with organ
dysfunction scores over 7 days, suggesting the presence of early, self
sustaining, pathologic inflammation involving high-mobility group protein B1,
interleukin-23, and the Th17 pathway. Survivors demonstrated a pattern
commensurate with a self-resolving, predominantly lymphoid response, including
higher levels of the reparative cytokine interleukin-22. Mice subjected to
trauma/hemorrhage exhibited reduced organ damage when treated with anti
interleukin-17A. CONCLUSIONS: Variable type 17 immune responses are hallmarks of
organ damage, survival, and mortality after blunt trauma and suggest a lymphoid
cell-based switch from self-resolving to self-sustaining inflammation.
PMID- 27513539
TI - Long-Term Survival Rate in Patients With Acute Respiratory Failure Treated With
Noninvasive Ventilation in Ordinary Wards.
AB - OBJECTIVE: Noninvasive ventilation is a life-saving technique increasingly used
to treat acute respiratory failure. Noninvasive ventilation has been applied
mostly in ICUs, but several reasons brought to an increasing application of
noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of
patients receiving noninvasive ventilation including long-term follow-up. The aim
of the present study was to assess 1-year survival rate of patients treated with
noninvasive ventilation outside the ICU for acute respiratory failure of
heterogeneous causes and to identify the predictors of long-term mortality.
DESIGN: Prospective, observational, pragmatic study. SETTING: Ordinary wards of a
teaching hospital. PATIENTS: Consecutive patients treated with noninvasive
ventilation for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND
MAIN RESULTS: Two-hundred and twenty-patients were enrolled. Mortality rates at
30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding
patients with "do-not-resuscitate" status, mortality rates were 13%, 19%, and
28%. The multivariate analyses identified solid cancer, pneumonia in hematologic
patients, and do-not-resuscitate status as independent predictors of mortality
with postoperative acute respiratory failure associated with improved survival.
The same predictors were confirmed when excluding do-not-resuscitate patients
from the analyses. CONCLUSIONS: Noninvasive ventilation applied in ordinary wards
was effective, with long-term outcomes not different from those reported for ICU
settings. Solid cancer, pneumonia in hematologic malignancies, and do-not
resuscitate status predicted mortality, whereas patients with postoperative acute
respiratory failure had the best survival rate. Additional studies are required
to evaluate noninvasive ventilation efficacy in the wards compared with ICU.
PMID- 27513540
TI - Long-Term Mental Health Problems After Delirium in the ICU.
AB - OBJECTIVES: To determine whether delirium during ICU stay is associated with long
term mental health problems defined as symptoms of anxiety, depression, and
posttraumatic stress disorder. DESIGN: Prospective cohort study. SETTING: Survey
study, 1 year after discharge from a medical-surgical ICU in the Netherlands.
PATIENTS: One-year ICU survivors of an ICU admission lasting more than 48 hours,
without a neurologic disorder or other condition that would impede delirium
assessment during ICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
One year after discharge, ICU survivors received a survey containing the Hospital
Anxiety and Depression Scale with a subscale for symptoms of depression and a
subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring
symptoms of posttraumatic stress disorder. Participants were classified as having
experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%),
or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial
regression was used to assess the association between delirium and symptoms of
anxiety, depression, and posttraumatic stress disorder. The study population
consisted of 567 subjects; of whom 246 subjects (43%) reported symptoms of
anxiety (Hospital Anxiety and Depression Scale with a subscale for anxiety, >=
8), and 254 (45%) symptoms of depression (Hospital Anxiety and Depression Scale
with a subscale for depression, >= 8). In 220 patients (39%), the Impact of Event
Scale 15 item was greater than or equal to 35, indicating a high probability of
posttraumatic stress disorder. There was substantial overlap between these mental
health problems-63% of the subjects who scored positive for the presence of any
three of the mental health problems, scored positive for all three. No
association was observed between either a single day or multiple days of delirium
and symptoms of anxiety, depression, or posttraumatic stress disorder.
CONCLUSIONS: Although symptoms of anxiety, depression, and posttraumatic stress
disorder were found to be common 1 year after critical illness, the occurrence of
delirium during ICU stay did not increase the risk of these long-term mental
health problems.
PMID- 27513541
TI - Increased Ratio of Visceral to Subcutaneous Adipose Tissue in Septic Patients Is
Associated With Adverse Outcome.
AB - OBJECTIVES: Visceral and subcutaneous adipose tissue may contribute
differentially to the septic inflammatory response. Accordingly, we tested the
hypothesis that the ratio of visceral to subcutaneous adipose tissue is
associated with altered sepsis outcome. DESIGN: A retrospective analysis from a
cohort of sepsis patients admitted between 2004 and 2009. SETTING: A mixed
medical-surgical ICU at St. Paul's Hospital in Vancouver, Canada. PATIENTS:
Patients older than 16 years old who had sepsis and underwent abdominal CT scan
(n = 257) for clinical reasons. INTERVENTIONS: None. MEASUREMENTS AND MAIN
RESULTS: We measured the visceral adipose tissue and subcutaneous adipose tissue
areas and calculated the visceral adipose tissue-to-subcutaneous adipose tissue
ratio. Visceral adipose tissue/subcutaneous adipose tissue was not correlated
with body mass index (r = -0.015, p = NS) and therefore provides additional
unique information independent of body mass index. Sepsis patients with higher
visceral adipose tissue/subcutaneous adipose tissue had greater 90-day mortality
than patients with lower visceral adipose tissue/subcutaneous adipose tissue (log
rank test, linear-by linear association p < 0.005). After adjustment for
significant covariates using Cox regression, increased visceral adipose
tissue/subcutaneous adipose tissue quartile was significantly associated with
increased 90-day mortality with hazard ratios of 2.01 (95% CI, 1.01-3.99) for the
third visceral adipose tissue/subcutaneous adipose tissue quartile compared with
the first quartile and 2.32 (95% CI, 1.15-4.69) for the highest visceral adipose
tissue/subcutaneous adipose tissue quartile when compared with the first
quartile. Increased mortality for patients with higher visceral adipose
tissue/subcutaneous adipose tissue was found for both patients with body mass
index less than 25 kg/m (p = 0.004) and for body mass index greater than or equal
to 25 kg/m (p = 0.023). Furthermore, we found significantly greater need for
mechanical ventilation, renal replacement therapy, and ICU stay in patients in
the highest visceral adipose tissue/subcutaneous adipose tissue quartile. The
ratio of proinflammatory (interleukin-8) to anti-inflammatory (interleukin-10)
plasma cytokine levels was greater in patients with higher visceral adipose
tissue/subcutaneous adipose tissue than in those with lower visceral adipose
tissue/subcutaneous adipose tissue (p = 0.043). CONCLUSIONS: Visceral obesity,
defined by a high visceral adipose tissue-to-subcutaneous adipose tissue ratio,
contributes to adverse outcome in sepsis patients perhaps because of a greater
pro- versus anti-inflammatory response.
PMID- 27513542
TI - Peripheral IV Insulin Infusion Infiltration Presenting as "Insulin Resistance".
AB - OBJECTIVES: We present the case of a 66-year-old woman who developed hypoglycemia
following the prolonged infiltration of a high dose continuous peripheral IV
insulin infusion. STUDY SELECTION: Case report. DATA SOURCES AND EXTRACTION:
PubMed was searched for relevant literature on exogenous hyperinsulinemic
hypoglycemia. DATA SYNTHESIS: The patient was postlung transplantation and was
receiving high doses of glucocorticoids. Despite increasing the peripheral IV
insulin rate, hyperglycemia persisted. We discovered that the IV insulin infusion
line infiltrated, resulting in a large subcutaneous insulin depot, estimated to
be 450 units of regular insulin. She subsequently experienced prolonged
hypoglycemia that was managed with concentrated dextrose containing fluids. In
our literature search, there were no similar case reports. The literature on
insulin overdose, usually from suicide attempts, can help guide the management of
iatrogenic hyperinsulinemic hypoglycemia. Important management considerations
include anticipated duration of hypoglycemia, supplemental glucose, fluid
management, and electrolyte monitoring. CONCLUSION: Peripheral IV insulin
infusion infiltration should be considered when patients do not respond to
increasing rates of insulin infusion.
PMID- 27513543
TI - Protocolized Sepsis Care Is Not Helpful for Patients.
PMID- 27513544
TI - The Target Temperature for Post Cardiac Arrest Patients Should Be 36 degrees C.
PMID- 27513545
TI - Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical
Illness: A Systematic Review and Meta-Analysis.
AB - OBJECTIVE: The relationship between neuromuscular blocking agents and
neuromuscular dysfunction acquired in critical illness remains unclear. We
examined the association between neuromuscular blocking agents and ICU-acquired
weakness, critical illness polyneuropathy, and critical illness myopathy. DATA
SOURCES: PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled
Trials, Cumulative Index of Nursing and Allied Health Literature, and
bibliographies of included studies were searched from database inception until
September 24, 2015. STUDY SELECTION: Randomized controlled trials and prospective
observational studies examining the association between neuromuscular blocking
agents and ICU-acquired weakness, critical illness polyneuropathy, or critical
illness myopathy. DATA EXTRACTION: One author screened titles/abstracts. Two
authors independently reviewed full text and extracted data from included
studies. Meta-analysis was performed using the DerSimonian-Laird random effects
model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel
plots and heterogeneity with the I statistic. DATA SYNTHESIS: Of 2,170
titles/abstracts screened, 99 full texts were selected for review, yielding one
randomized controlled trial and 18 prospective observational studies, for a total
of 2,254 patients. The randomized controlled trial did not show an association
between neuromuscular blocking agents and neuromuscular dysfunction acquired in
critical illness (odds ratio, 1.21; 95% CI, 0.67-2.19), but pooled data from all
included studies suggested a modest association (odds ratio, 1.25; 95% CI, 1.06
1.48; I = 16%). Funnel plots suggested reporting bias, and sensitivity analyses
showed a disproportionate contribution from critical illness
polyneuropathy/critical illness myopathy and severe sepsis/septic shock studies.
CONCLUSIONS: This meta-analysis suggests a modest association between
neuromuscular blocking agents and neuromuscular dysfunction acquired in critical
illness; limitations include studies with a high risk of bias and a
disproportionate contribution from studies examining patients for critical
illness polyneuropathy/critical illness myopathy and those with severe
sepsis/septic shock.
PMID- 27513546
TI - Comparing Time-Fixed Mortality Prediction Models and Their Effect on ICU
Performance Metrics Using the Simplified Acute Physiology Score 3.
AB - OBJECTIVES: To examine ICU performance based on the Simplified Acute Physiology
Score 3 using 30-day, 90-day, or 180-day mortality as outcome measures and
compare results with 30-day mortality as reference. DESIGN: Retrospective cohort
study of ICU admissions from 2010 to 2014. SETTING: Sixty-three Swedish ICUs that
submitted data to the Swedish Intensive Care Registry. PATIENTS: The development
cohort was first admissions to ICU during 2011-2012 (n = 53,546), and the
validation cohort was first admissions to ICU during 2013-2014 (n = 57,729).
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Logistic regression was used
to develop predictive models based on a first level recalibration of the original
Simplified Acute Physiology Score 3 model but with 30-day, 90-day, or 180-day
mortality as measures of outcome. Discrimination and calibration were excellent
for the development dataset. Validation in the more recent 2013-2014 database
showed good discrimination (C-statistic: 0.85, 0.84, and 0.83 for the 30-, 90-,
and 180-d models, respectively), and good calibration (standardized mortality
ratio: 0.99, 0.99, and 1.00; Hosmer-Lemeshow goodness of fit H-statistic: 66.4,
63.7, and 81.4 for the 30-, 90-, and 180-d models, respectively). There were
modest changes in an ICU's standardized mortality ratio grouping (< 1.00, not
significant, > 1.00) when follow-up was extended from 30 to 90 days and 180 days,
respectively; about 11-13% of all ICUs. CONCLUSIONS: The recalibrated Simplified
Acute Physiology Score 3 hospital outcome prediction model performed well on long
term outcomes. Evaluation of ICU performance using standardized mortality ratio
was only modestly sensitive to the follow-up time. Our results suggest that 30
day mortality may be a good benchmark of ICU performance. However, the duration
of follow-up must balance between what is most relevant for patients, most
affected by ICU care, least affected by administrative policies and practically
feasible for caregivers.
PMID- 27513547
TI - A Comparison of the Ability of the Physiologic Components of Medical Emergency
Team Criteria and the U.K. National Early Warning Score to Discriminate Patients
at Risk of a Range of Adverse Clinical Outcomes.
AB - OBJECTIVE: To compare the ability of medical emergency team criteria and the
National Early Warning Score to discriminate cardiac arrest, unanticipated ICU
admission and death within 24 hours of a vital signs measurement, and to quantify
the associated workload. DESIGN: Retrospective cohort study. SETTING: A large
U.K. National Health Service District General Hospital. PATIENTS: Adults
hospitalized from May 25, 2011, to December 31, 2013. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: We applied the National Early Warning Score and 44
sets of medical emergency team criteria to a database of 2,245,778 vital signs
sets (103,998 admissions). The National Early Warning Score's performance was
assessed using the area under the receiver-operating characteristic curve and
compared with sensitivity/specificity for different medical emergency team
criteria. Area under the receiver-operating characteristic curve (95% CI) for the
National Early Warning Score for the combined outcome (i.e., death, cardiac
arrest, or unanticipated ICU admission) was 0.88 (0.88-0.88). A National Early
Warning Score value of 7 had sensitivity/specificity values of 44.5% and 97.4%,
respectively. For the 44 sets of medical emergency team criteria studied,
sensitivity ranged from 19.6% to 71.2% and specificity from 71.5% to 98.5%. For
all outcomes, the position of the National Early Warning Score receiver-operating
characteristic curve was above and to the left of all medical emergency team
criteria points, indicating better discrimination. Similarly, the positions of
all medical emergency team criteria points were above and to the left of the
National Early Warning Score efficiency curve, indicating higher workloads
(trigger rates). CONCLUSIONS: When medical emergency team systems are compared to
a National Early Warning Score value of greater than or equal to 7, some medical
emergency team systems have a higher sensitivity than National Early Warning
Score values of greater than or equal to 7. However, all of these medical
emergency team systems have a lower specificity and would generate greater
workloads.
PMID- 27513548
TI - Cardiac Ultrasound Is a Competency of Critical Care Medicine.
PMID- 27513549
TI - Fate of the drug chlorpromazine in river water according to laboratory assays.
Identification and evolution over time of degradation products. Sorption to
sediment.
AB - Toxic effects of the non-biodegradable drug chlorpromazine and its degradation
products have been reported on microorganisms in aqueous media. Here,
chlorpromazine degradation assays in forced and non-forced conditions have been
done to know its persistence and degradation products in river water. Sunlight
irradiation promotes the complete degradation of chlorpromazine (2 MUg L(-1)) in
less than 4 h, but if the exposure to sunlight is limited chlorpromazine is
detected during 4 weeks in river water. Sixteen degradation products in surface
water are described for first time after solid-phase extraction and analysis by
ultra-pressure liquid chromatography/quadrupole time-of-flight/mass spectrometry;
their structures are proposed from the molecular formulae of the fragment-ions
observed in high-resolution tandem mass spectra. Hydroxylation and oxidation
products such as chlorpromazine sulfoxide, 2-hydroxypromazine and 2
hydroxypromazine sulfoxide were predominant degradation products in the early
stages; some benzo[1,4]thiazin-6-ol derivatives resulting from the breakdown of
the phenothiazine core were the major and relatively stable products after 20
weeks under non-forced conditions. A degradation pathway of chlorpromazine in
water is outlined. Moreover, it is shown that chlorpromazine is very strongly
adsorbed on sediment while the degradation products that kept the promazine core
have a notable capacity of sorption, too; sorption coefficients are calculated.
Finally, a prediction about the toxicity of the degradation products in aquatic
ecosystems suggests that some of them have toxicities similar, or even higher,
than chlorpromazine.
PMID- 27513550
TI - Copper accumulation in vineyard soils: Rhizosphere processes and agronomic
practices to limit its toxicity.
AB - Viticulture represents an important agricultural practice in many countries
worldwide. Yet, the continuous use of fungicides has caused copper (Cu)
accumulation in soils, which represent a major environmental and toxicological
concern. Despite being an important micronutrient, Cu can be a potential toxicant
at high concentrations since it may cause morphological, anatomical and
physiological changes in plants, decreasing both food productivity and quality.
Rhizosphere processes can, however, actively control the uptake and translocation
of Cu in plants. In particular, root exudates affecting the chemical, physical
and biological characteristics of the rhizosphere, might reduce the availability
of Cu in the soil and hence its absorption. In addition, this review will aim at
discussing the advantages and disadvantages of agronomic practices, such as
liming, the use of pesticides, the application of organic matter, biochar and
coal fly ashes, the inoculation with bacteria and/or mycorrhizal fungi and the
intercropping, in alleviating Cu toxicity symptoms.
PMID- 27513551
TI - Dermal uptake and percutaneous penetration of ten flame retardants in a human
skin ex vivo model.
AB - The dermal uptake and percutaneous penetration of ten organic flame retardants
was measured using an ex vivo human skin model. The studied compounds were DBDPE,
BTBPE, TBP-DBPE, EH-TBB, BEH-TEBP, alpha, beta and gamma-HBCDD as well as syn-
and anti-DDC-CO. Little or none of the applied flame retardants was recovered in
either type of the receptor fluids used (physiological and worst-case). However,
significant fractions were recovered in the skin depot, particularly in the upper
skin layers. The primary effect of the worst-case receptor fluid was deeper
penetration into the skin. The recovered mass was used to calculate lower- and
upper-bound permeability coefficients kp. Despite large structural variation
between the studied compounds, a clear, significant decreasing trend of kp was
observed with increasing log Kow. The results indicate that the dermis may
provide a significant barrier for these highly lipophilic compounds. However,
based on our results, dermal uptake should be considered in exposure assessments,
though it may proceed in a time-lagged manner compared to less hydrophobic
compounds.
PMID- 27513552
TI - Utilization of phosphorus loaded alkaline residue to immobilize lead in a
shooting range soil.
AB - The alkaline residue generated from the production of soda ash using the ammonia
soda method has been successfully used in removing phosphorus (P) from aqueous
solution. But the accumulation of P-containing solid after P removal is an
undesirable menace to the environment. To achieve the goal of recycling, this
study explored the feasibility of reusing the P loaded alkaline residue as an
amendment for immobilization of lead (Pb) in a shooting range soil. The main
crystalline phase and micromorphology of amendments were determined using X-ray
diffraction (XRD) and scanning electron microscopy-electron dispersion
spectroscopy (SEM-EDS) methods. The toxicity characteristic leaching procedure
(TCLP), sequential extraction procedure, and physiologically based extraction
test (PBET) were employed to evaluate the effectiveness of Pb immobilization in
soil after 45 d incubation. Treatment with P loaded alkaline residue was
significantly effective in reducing the TCLP and PBET extractable Pb
concentrations in contrast to the untreated soil. Moreover, a positive change in
the distribution of Pb fractions was observed in the treated soil, i.e., more
than 60% of soil-Pb was transformed to the residual fraction compared to the
original soil. On the other hand, P loaded amendments also resulted in a drastic
reduction in phytoavailable Pb to the winter wheat and a mild release of P as a
nutrient in treated soil, which also confirmed the improvement of soil quality.
PMID- 27513553
TI - Outdoor air pollution and human infertility: a systematic review.
AB - Air pollution is a current research priority because of its adverse effects on
human health, including on fertility. However, the mechanisms through which air
pollution impairs fertility remain unclear. In this article, we perform a
systematic review to evaluate currently available evidence on the impact of air
pollution on fertility in humans. Several studies have assessed the impact of air
pollutants on the general population, and have found reduced fertility rates and
increased risk of miscarriage. In subfertile patients, women exposed to higher
concentrations of air pollutants while undergoing IVF showed lower live birth
rates and higher rates of miscarriage. After exposure to similar levels of air
pollutants, comparable results have been found regardless of the mode of
conception (IVF versus spontaneous conception), suggesting that infertile women
are not more susceptible to the effects of pollutants than the general
population. In addition, previous studies have not observed impaired embryo
quality after exposure to air pollution, although evidence for this question is
sparse.
PMID- 27513555
TI - Systems metabolic engineering of Escherichia coli for the heterologous production
of high value molecules-a veteran at new shores.
AB - For more than fifty years, Escherichia coli has represented a remarkable success
story in industrial biotechnology. Traditionally known as a producer of l-amino
acids, E. coli has also entered the precious market of high-value molecules and
is becoming a flexible, efficient production platform for various therapeutics,
pre-biotics, nutraceuticals and pigments. This tremendous progress is enabled by
systems metabolic engineering concepts that integrate systems biology and
synthetic biology into the design and engineering of powerful E. coli cell
factories.
PMID- 27513556
TI - Transplantation of Pro-Oligodendroblasts, Preconditioned by LPS-Stimulated
Microglia, Promotes Recovery After Acute Contusive Spinal Cord Injury.
AB - Spinal cord injury (SCI) is a significant clinical challenge, and to date no
effective treatment is available. Oligodendrocyte progenitor cell (OPC)
transplantation has been a promising strategy for SCI repair. However, the poor
posttransplantation survival and deficiency in differentiation into myelinating
oligodendrocytes (OLs) are two major challenges that limit the use of OPCs as
donor cells. Here we report the generation of an OL lineage population [i.e., pro
oligodendroblasts (proOLs)] that is relatively more mature than OPCs for
transplantation after SCI. We found that proOLs responded to lipopolysaccharide
(LPS)-stimulated microglia conditioned medium (L+M) by preserving toll-like
receptor 4 (TLR4) expression, improving cell viability, and enhancing the
expression of a myelinating OL marker myelin basic protein (MBP), compared to
other OL lineage cells exposed to either LPS-stimulated (L+M) or nonstimulated
microglia conditioned medium (LM). When L+M-stimulated proOLs were intrathecally
delivered through a lumbar puncture after a T10 thoracic contusive SCI, they
promoted behavioral recovery, as assessed by the BassoBeattieBresnahan (BBB)
locomotor rating scale, stride length, and slips on the grid tests.
Histologically, transplantation of L+M proOLs caused a considerable increase in
intralesional axon numbers and myelination, and less accumulation of invading
macrophages when compared with the vehicle control or OPC transplantation. Thus,
transplantation of proOLs, preconditioned by L+M, may offer a better therapeutic
potential for SCI than OPCs since the former may have initiated the
differentiation process toward OLs prior to transplantation.
PMID- 27513554
TI - Environmental influences on reproductive health: the importance of chemical
exposures.
AB - Chemical exposures during pregnancy can have a profound and life-long impact on
human health. Because of the omnipresence of chemicals in our daily life, there
is continuous contact with chemicals in food, water, air, and consumer products.
Consequently, human biomonitoring studies show that pregnant women around the
globe are exposed to a variety of chemicals. In this review we provide a summary
of current data on maternal and fetal exposure, as well as health consequences
from these exposures. We review several chemical classes, including
polychlorinated biphenyls, perfluoroalkyl substances, polybrominated diphenyl
ethers, phenols, phthalates, pesticides, and metals. Additionally, we discuss
environmental disparities and vulnerable populations, and future research
directions. We conclude by providing some recommendations for prevention of
chemical exposure and its adverse reproductive health consequences.
PMID- 27513557
TI - 5-Azacytidine suppresses EC9706 cell proliferation and metastasis by upregulating
the expression of SOX17 and CDH1.
AB - 5-Azacytidine is a well-known anticancer drug that is clinically used in the
treatment of breast cancer, melanoma and colon cancer. It has been reported that
5-azacytidine suppresses the biological behavior of esophageal cancer cells.
However, corresponding mechanisms remain unclear. In this study, using Transwell
invasion and cell proliferation assays, we demonstrated that 5-azacytidine
significantly inhibited the metastasis and proliferation of EC9706 cells, and
upregulated the expression of cadherin 1 (CDH1) and SRY-box containing gene 17
(SOX17). Moreover, the inhibition of the metastasis of the 5-azacytidine-treated
EC9706 cells was impaired following transfection with siRNA targeting CDH1 (CDH1
siRNA), and the inhibition of cell proliferation was attenuated following the
downregulation of SOX17 by siRNA targeting SOX17 (SOX17 siRNA). Furthermore, 5
azacytidine remarkably reduced the CDH1 and SOX17 promoter methylation levels,
suggesting that 5-azacytidine upregulates the expression of SOX17 and CDH1 by
inhibiting the methylation of the SOX17 and CDH1 promoter. The findings of our
study confirm that 5-azacytidine suppresses the proliferation and metastasis of
EC9706 esophageal cancer cells by upregulating the expression of CDH1 and SOX17.
The expression levels of CDH1 and SOX17 negatively correlate with the promoter
methylation levels. CDH1 and SOX17 are potential indicators of the clinical
application of 5-azacytidine.
PMID- 27513558
TI - The Economic Value of the Greater Montreal Blue Network (Quebec, Canada): A
Contingent Choice Study Using Real Projects to Estimate Non-Market Aquatic
Ecosystem Services Benefits.
AB - This study used a contingent choice method to determine the economic value of
improving various ecosystem services (ESs) of the Blue Network of Greater
Montreal (Quebec, Canada). Three real projects were used and the evaluation
focused on six ESs that are related to freshwater aquatic ecosystems:
biodiversity, water quality, carbon sequestration, recreational activities,
landscape aesthetics and education services. We also estimated the value
associated with the superficies of restored sites. We calculated the monetary
value that a household would be willing to pay for each additional qualitative or
quantitative unit of different ESs, and these marginal values range from $0.11 to
$15.39 per household per unit. Thus, under certain assumptions, we determined the
monetary values that all Quebec households would allocate to improve each ES in
Greater Montreal by one unit. The most valued ES was water quality ($13.5
million), followed by education services ($10.7 million), recreational activities
($8.9 million), landscape aesthetics ($4.1 million), biodiversity ($1.2 million),
and carbon sequestration ($0.1 million). Our results ascribe monetary values to
improved (or degraded) aquatic ecosystems in the Blue Network of Greater
Montreal, but can also enhance economic analyses of various aquatic ecosystem
restoration and management projects.
PMID- 27513559
TI - Comparative Genomic Analyses Provide New Insights into the Evolutionary Dynamics
of Heterochromatin in Drosophila.
AB - The term heterochromatin has been long considered synonymous with gene silencing,
but it is now clear that the presence of transcribed genes embedded in
pericentromeric heterochromatin is a conserved feature in the evolution of
eukaryotic genomes. Several studies have addressed the epigenetic changes that
enable the expression of genes in pericentric heterochromatin, yet little is
known about the evolutionary processes through which this has occurred. By
combining genome annotation analysis and high-resolution cytology, we have
identified and mapped 53 orthologs of D. melanogaster heterochromatic genes in
the genomes of two evolutionarily distant species, D. pseudoobscura and D.
virilis. Our results show that the orthologs of the D. melanogaster
heterochromatic genes are clustered at three main genomic regions in D. virilis
and D. pseudoobscura. In D. virilis, the clusters lie in the middle of
euchromatin, while those in D. pseudoobscura are located in the proximal portion
of the chromosome arms. Some orthologs map to the corresponding Muller C element
in D. pseudoobscura and D. virilis, while others localize on the Muller B
element, suggesting that chromosomal rearrangements that have been instrumental
in the fusion of two separate elements involved the progenitors of genes
currently located in D. melanogaster heterochromatin. These results demonstrate
an evolutionary repositioning of gene clusters from ancestral locations in
euchromatin to the pericentromeric heterochromatin of descendent D. melanogaster
chromosomes. Remarkably, in both D. virilis and D. pseudoobscura the gene
clusters show a conserved association with the HP1a protein, one of the most
highly evolutionarily conserved epigenetic marks. In light of these results, we
suggest a new scenario whereby ancestral HP1-like proteins (and possibly other
epigenetic marks) may have contributed to the evolutionary repositioning of gene
clusters into heterochromatin.
PMID- 27513560
TI - Posttranslational Modifications of NPR1: A Single Protein Playing Multiple Roles
in Plant Immunity and Physiology.
PMID- 27513561
TI - Hydrodynamic trapping for rapid assembly and in situ electrical characterization
of droplet interface bilayer arrays.
AB - The droplet interface bilayer (DIB) is a modular technique for assembling planar
lipid membranes between water droplets in oil. The DIB method thus provides a
unique capability for developing digital, droplet-based membrane platforms for
rapid membrane characterization, drug screening and ion channel recordings. This
paper demonstrates a new, low-volume microfluidic system that automates droplet
generation, sorting, and sequential trapping in designated locations to enable
the rapid assembly of arrays of DIBs. The channel layout of the device is guided
by an equivalent circuit model, which predicts that a serial arrangement of
hydrodynamic DIB traps enables sequential droplet placement and minimizes the
hydrodynamic pressure developed across filled traps to prevent squeeze-through of
trapped droplets. Furthermore, the incorporation of thin-film electrodes
fabricated via evaporation metal deposition onto the glass substrate beneath the
channels allows for the first time in situ, simultaneous electrical interrogation
of multiple DIBs within a sealed device. Combining electrical measurements with
imaging enables measurements of membrane capacitance and resistance and bilayer
area, and our data show that DIBs formed in different trap locations within the
device exhibit similar sizes and transport properties. Simultaneous, single
channel recordings of ion channel gating in multiple membranes are obtained when
alamethicin peptides are incorporated into the captured droplets, qualifying the
thin-film electrodes as a means for measuring stimuli-responsive functions of
membrane-bound biomolecules. This novel microfluidic-electrophysiology platform
provides a reproducible, high throughput method for performing electrical
measurements to study transmembrane proteins and biomembranes in low-volume,
droplet-based membranes.
PMID- 27513562
TI - Anti-Hyperglycemic Agents and New-Onset Acute Myocardial Infarction in Diabetic
Patients with End-Stage Renal Disease Undergoing Dialysis.
AB - BACKGROUND: Diabetes and chronic kidney disease (CKD) are a high-stakes
combination for cardiovascular disease. Patients with decreased kidney function
and end-stage renal disease (ESRD) have increased risk of hypoglycemia when
attaining better glycemic control, leading to higher risk of myocardial
infarction (MI). For these patients, which kinds of anti-hyperglycemic agents
would be associated with higher risk of MI is not clear. METHODS: We identified
patients from a nation-wide database called Registry for Catastrophic Illness,
which encompassed almost 100% of the patients receiving dialysis therapy in
Taiwan from 1995 to 2008. Patients with diabetes and ESRD were selected as the
study cohort. Propensity score adjustment and Cox's proportional hazards
regression model were used to estimate the hazard ratios (HRs) for new-onset MI.
RESULTS: Among 15,161 patients, 39% received insulin, 40% received sulfonylureas,
18% received meglitinides and 3% received thiazolidinedione (TZD). After a median
follow-up of 1,357 days, the incidence of MI was significant increase in patients
taking sulfonylureas (HR = 1.523, 95% confidence interval [CI] = 1.331-1.744),
meglitinides (HR = 1.251, 95% CI = 1.048-1.494) and TZD (HR = 1.515, 95% CI =
1.071-2.145) by using patients receiving insulin therapy as the reference group.
The risk of MI remains higher in other three groups in subgroup analyses.
CONCLUSIONS: In conclusion, among diabetic patients with ESRD undergoing
dialysis, the use of sulfonylureas, meglitinides and TZD are associated with
higher risk of new-onset MI as compared with insulin.
PMID- 27513563
TI - Development of a New Limiting-Antigen Avidity Dot Immuno-Gold Filtration Assay
for HIV-1 Incidence.
AB - Several laboratory assays on cross-sectional specimens for detecting recent HIV
infections were developed, but these assays could not be applied in resource
limited and high HIV-incidence areas. This study describes the development of a
rapid assay that can simultaneously detect the presence of HIV-1 antibodies of
current and/or recent infection. The dot immuno-gold filtration assay (DIGFA) was
used to detect recent infection on the principle of antibody avidity changes
between recent and long-term infections. The dot immuno-gold silver staining
filtration assay (DIGSSA) increases the sensitivity and accuracy of antibody
detection by adding a silver staining step to the DIGFA. In the meantime the
digital results were produced by the scanner for ambiguous specimens. Further,
HIV-1 routine diagnostic antibody was detected simultaneously for improving
practicability. The performance of the assays was then assessed through five
serum panels with known serological statuses and seroconversion dates. The
proportion of false recent infection (PFR) of the DIGSSA was obtained. Through
the optimization of basic parameters for DIGSSA, six specimens were all
classified correctly. DIGSSA demonstrated good repeatability and high
sensitivity. The agreement of DIGSSA with the BED assay was 92.10% (kappa = 0.65)
and 95.36% with the LAg-Avidity assay (kappa = 0.75). Moreover, the gray values
of DIGSSA correlated well with BED ODn (R2 = 0.9397) and LAg-Avidity ODn (R2 =
0.9549). The PFR of DIGSSA was 2.73%, which was lower than that of the BED assay
but higher than that of the LAg-Avidity assay. The DIGSSA can feasibly be applied
to detect HIV infection and estimate HIV incidence.
PMID- 27513564
TI - Altered Immune Profiles of Natural Killer Cells in Chronic Hepatitis B Patients:
A Systematic Review and Meta-Analysis.
AB - BACKGROUND: Natural killer (NK) cells are the main effective component of the
innate immune system that responds to chronic hepatitis B (CHB) infection.
Although numerous studies have reported the immune profiles of NK cells in CHB
patients, they are limited by inconsistent results. Thus, we performed a meta
analysis to characterize reliably the immune profiles of NK cells after CHB
infection, specifically frequency, phenotype, and function. METHODS: A literature
search of the computer databases MEDLINE, PUBMED, EMBASE, and Cochrane Center
Register of Controlled Trails was performed and 19 studies were selected. The
standard mean difference (SMD) and 95% confidence interval (CI) of each
continuous variable was estimated with a fixed effects model when I2 < 50% for
the test for heterogeneity, or the random effects model otherwise. Publication
bias was evaluated using Begg's and Egger's tests. RESULTS: The meta-analysis of
publications that reported frequency of peripheral NK cells showed that NK cell
levels in CHB patients were significantly lower compared with that of healthy
controls. A higher frequency of CD56bright NK subsets was found in CHB patients,
but the CD56dim NK subsets of CHB patients and healthy controls were similar. CHB
patients before and after antiviral therapy with nucleotide analogues (NUCs)
showed no statistical difference in NK frequency. The activating receptors were
upregulated, whereas inhibitory receptors were comparable in the peripheral NK
cells of CHB individuals and healthy controls. NK cells of CHB patients displayed
higher cytotoxic potency as evidenced by CD107a protein levels and conserved
potency to produce interferon-gamma (IFNgamma), compared with their healthy
counterparts. CONCLUSION: Our results revealed that CHB patients had a lower
frequency of NK cells compared with healthy individuals not treatable with
antiviral NUC therapy. With an activating phenotype, NK cells in CHB patients
showed better cytotoxic potency and conserved IFNgamma production.
PMID- 27513565
TI - Projecting the Global Distribution of the Emerging Amphibian Fungal Pathogen,
Batrachochytrium dendrobatidis, Based on IPCC Climate Futures.
AB - Projected changes in climate conditions are emerging as significant risk factors
to numerous species, affecting habitat conditions and community interactions.
Projections suggest species range shifts in response to climate change modifying
environmental suitability and is supported by observational evidence. Both
pathogens and their hosts can shift ranges with climate change. We consider how
climate change may influence the distribution of the emerging infectious
amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), a pathogen
associated with worldwide amphibian population losses. Using an expanded global
Bd database and a novel modeling approach, we examined a broad set of climate
metrics to model the Bd-climate niche globally and regionally, then project how
climate change may influence Bd distributions. Previous research showed that Bd
distribution is dependent on climatic variables, in particular temperature. We
trained a machine-learning model (random forest) with the most comprehensive
global compilation of Bd sampling records (~5,000 site-level records, mid-2014
summary), including 13 climatic variables. We projected future Bd environmental
suitability under IPCC scenarios. The learning model was trained with combined
worldwide data (non-region specific) and also separately per region (region
specific). One goal of our study was to estimate of how Bd spatial risks may
change under climate change based on the best available data. Our models
supported differences in Bd-climate relationships among geographic regions. We
projected that Bd ranges will shift into higher latitudes and altitudes due to
increased environmental suitability in those regions under predicted climate
change. Specifically, our model showed a broad expansion of areas environmentally
suitable for establishment of Bd on amphibian hosts in the temperate zones of the
Northern Hemisphere. Our projections are useful for the development of monitoring
designs in these areas, especially for sensitive species and those vulnerable to
multiple threats.
PMID- 27513566
TI - sIgE Ana o 1, 2 and 3 accurately distinguish tolerant from allergic children
sensitized to cashew nuts.
AB - BACKGROUND: The double-blind, placebo-controlled food challenge test (DBPCFC) is
the gold standard in cashew nut allergy. This test is costly, time consuming and
not without side effects. Analysis of IgE reactivity to cashew nut components may
reduce the need for food challenge tests. METHODS: In a prospective and
multicentre study, children with suspected cashew nut allergy underwent a DBPCFC
with cashew nut. Specific IgE to cashew nut and to the components Ana o 1, 2 and
3 were determined. A skin prick test (SPT) with cashew nut extract was performed.
The association between the outcome of the food challenge test and specific IgE
to Ana o 1, 2 and 3 was assessed with logistic regression analyses, unadjusted
and adjusted for other diagnostic variables. Discriminative ability was
quantified with a concordance index (c). RESULTS: A total of 173 children (103
boys, 60%) with a median age of 9 years were included. About 79% had a positive
challenge test outcome. A steep rise in the risk of a positive challenge was
observed for specific IgE to each individual component Ana o 1, 2 and 3 with
estimated risks up to approximately 100%. Median values of Ana o 1, 2, 3 were
1.29 kU/l (range 0-100 kU/l), 4.77 kU/l (range 0-100 kU/l) and 8.33 kU/l (range 0
100 kU/l) respectively and varied significantly (p < 0.001). Specific IgE to Ana
o 1, 2 and 3 was better distinguished between cashew-allergic and tolerant
children (c = 0.87, 0.85 and 0.89, respectively) than specific IgE to cashew nut
or SPT (c = 0.76 and 0.83, respectively). CONCLUSION: The major cashew nut
allergens Ana o 1, 2 and 3 are each individually predictive for the outcome of
food challenge tests in cashew-allergic children.
PMID- 27513567
TI - Reproducible Construction of Surface Tension-Mediated Honeycomb Concave Microwell
Arrays for Engineering of 3D Microtissues with Minimal Cell Loss.
AB - The creation of engineered 3D microtissues has attracted prodigious interest
because of the fact that this microtissue structure is able to mimic in vivo
environments. Such microtissues can be applied extensively in the fields of
regenerative medicine and tissue engineering, as well as in drug and toxicity
screening. Here, we develop a novel method of fabricating a large number of dense
honeycomb concave microwells via surface tension-mediated self-construction. More
specifically, in order to control the curvature and shape of the concavity in a
precise and reproducible manner, a custom-made jig system was designed and
fabricated. By applying a pre-set force using the jig system, the shape of the
honeycomb concave well was precisely and uniformly controlled, despite the fact
that wells were densely packed. The thin wall between the honeycomb wells enables
the minimization of cell loss during the cell-seeding process. To evaluate the
performance of the honeycomb microwell array, rat hepatocytes were seeded, and
spheroids were successfully formed with uniform shape and size. Liver-specific
functions such as albumin secretion and cytochrome P450 were subsequently
analyzed. The proposed method of fabricating honeycomb concave wells is cost
effective, simple, and reproducible. The honeycomb well array can produce
multiple spheroids with minimal cell loss, and can lead to significant
contributions in tissue engineering and organ regeneration.
PMID- 27513568
TI - Stimulation of Eryptosis by Caspofungin.
AB - BACKGROUND/AIMS: The echinocandin antifungal agent caspofungin has been shown to
trigger apoptosis of fungal cells. Beyond that, caspofungin is toxic for host
mitochondria. Even though lacking mitochondria, erythrocytes may enter apoptosis
like suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and
cell membrane scrambling with phosphatidylserine translocation to the erythrocyte
surface. Signaling involved in triggering of eryptosis include increase of
cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, caspase activation
and/or activation of p38 kinase, protein kinase C, and casein kinase. The present
study explored, whether caspofungin induces eryptosis and, if so, to shed some
light on the cellular mechanisms involved. METHODS: Flow cytometry was employed
to determine phosphatidylserine exposure at the cell surface from annexin-V
binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ROS
formation from DCFDA dependent fluorescence, and ceramide abundance utilizing
specific antibodies. Hemolysis was quantified from hemoglobin concentration in
the supernatant. RESULTS: A 48 hours exposure of human erythrocytes to
caspofungin (>= 30 ug/ml) significantly increased the percentage of annexin-V
binding cells, significantly decreased forward scatter, significantly enhanced
hemolysis, but did not significantly increase Fluo3-fluorescence, DCFDA
fluorescence or ceramide abundance. The effect of caspofungin on annexin-V
binding was not significantly blunted by removal of extracellular Ca2+, by
inhibition of caspases with pancaspase inhibitor zVAD (10 uM), or by addition of
the antioxidant N-acetyl-cysteine (1 mM), p38 kinase inhibitor SB203580 (2 uM) or
protein kinase C inhibitor staurosporine (1 uM). The effect of caspofungin on
annexin-V-binding was, however, significantly blunted in the presence of casein
kinase inhibitor D4476 (10 uM). CONCLUSIONS: Caspofungin triggers cell shrinkage
and phospholipid scrambling of the erythrocyte cell membrane, an effect possibly
involving activation of casein kinase.
PMID- 27513569
TI - Combination of chlorogenic acid and salvianolic acid B protects against
polychlorinated biphenyls-induced oxidative stress through Nrf2.
AB - Caffeic acid derivatives (CADs) are well-known phytochemicals with multiple
physiological and pharmacological activities. This study aimed to investigate the
combined protective effects of CADs on PCB126-induced liver damages and oxidative
stress in mice. Here, we used chemiluminescence and chose chlorogenic acid (CGA),
salvianolic acid B (Sal B) as the best antioxidants. Then, mice were
intragastrically administered with 60mg/kg/d CGA, Sal B, and CGA plus Sal B (1:1)
for 3 weeks before exposing to 0.05mg/kg/d PCB126 for 2 weeks. We found that
pretreatment with CGA, Sal B, and CGA plus Sal B effectively attenuated liver
injury and cytotoxicity caused by PCB126, but improved the expressions of
superoxide dismutase (SOD), glutathione reduced (GSH), heme oxygenase-1 (HO-1)
and nuclear factor E2-related factor 2 (Nrf2), CGA plus Sal B especially, was
found to have the best effects that indicated a synergetic protective effect.
Taken together, as the Nrf2 regulates the cyto-protective response by up
regulating the expression of antioxidant genes, we suggested that CGA plus Sal B
had a combined protection on PCB126-induced tissue damages and that the Nrf2
signaling might be involved.
PMID- 27513570
TI - Synthesis of High-Molecular-Weight Polyhydroxyalkanoates by Marine Photosynthetic
Purple Bacteria.
AB - Polyhydroxyalkanoate (PHA) is a biopolyester/bioplastic that is produced by a
variety of microorganisms to store carbon and increase reducing redox potential.
Photosynthetic bacteria convert carbon dioxide into organic compounds using light
energy and are known to accumulate PHA. We analyzed PHAs synthesized by 3 purple
sulfur bacteria and 9 purple non-sulfur bacteria strains. These 12 purple
bacteria were cultured in nitrogen-limited medium containing acetate and/or
sodium bicarbonate as carbon sources. PHA production in the purple sulfur
bacteria was induced by nitrogen-limited conditions. Purple non-sulfur bacteria
accumulated PHA even under normal growth conditions, and PHA production in 3
strains was enhanced by nitrogen-limited conditions. Gel permeation
chromatography analysis revealed that 5 photosynthetic purple bacteria
synthesized high-molecular-weight PHAs, which are useful for industrial
applications. Quantitative reverse transcription polymerase chain reaction
analysis revealed that mRNA levels of phaC and PhaZ genes were low under nitrogen
limited conditions, resulting in production of high-molecular-weight PHAs. We
conclude that all 12 tested strains are able to synthesize PHA to some degree,
and we identify 5 photosynthetic purple bacteria that accumulate high-molecular
weight PHA molecules. Furthermore, the photosynthetic purple bacteria synthesized
PHA when they were cultured in seawater supplemented with acetate. The
photosynthetic purple bacteria strains characterized in this study should be
useful as host microorganisms for large-scale PHA production utilizing abundant
marine resources and carbon dioxide.
PMID- 27513571
TI - Mortality in the First 3 Months on Antiretroviral Therapy Among HIV-Positive
Adults in Low- and Middle-income Countries: A Meta-analysis.
AB - Previous meta-analyses reported mortality estimates of 12-month post
antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the
first 3 months on ART, a more sensitive measure of averted deaths through early
ART initiation. To determine whether early mortality is dropping as treatment
thresholds have increased, we reviewed studies of 3 months on ART initiation in
low- to middle-income countries. Studies of 3-month mortality from January 2003
to April 2016 were searched in 5 databases. Articles were included that reported
3-month mortality from a low- to middle-income country; nontrial setting and
participants were >=15. We assessed overall mortality and stratified by year
using random effects models. Among 58 included studies, although not significant,
pooled estimates show a decline in mortality when comparing studies whose
enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the
studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce
early HIV-related mortality at the population level, intensified efforts to
increase demand for ART through active testing and facilitated referral should be
a priority. Continued financial investments by multinational partners and the
implementation of creative interventions to mitigate multidimensional complex
barriers of accessing care and treatment for HIV are needed.
PMID- 27513572
TI - Difference in Aortic Stiffness Between Treated Middle-Aged HIV Type 1-Infected
and Uninfected Individuals Largely Explained by Traditional Cardiovascular Risk
Factors, With an Additional Contribution of Prior Advanced Immunodeficiency.
AB - BACKGROUND: Patients with HIV, even with suppressed viremia on combination
antiretroviral therapy, are at increased risk for cardiovascular disease. The
underlying pathophysiology remains to be clarified. Aortic stiffness, known to be
associated with cardiovascular disease in the general population, was
investigated in a cohort of HIV type 1 (HIV 1)-infected and similar but
uninfected individuals. METHODS: Aortic stiffness was assessed by measuring pulse
wave velocity (PWV) with an Arteriograph. Five hundred seven HIV-uninfected and
566 HIV 1-infected individuals, predominantly with suppressed viremia on
combination antiretroviral therapy, aged >=45 years, participating in the ongoing
AGEhIV Cohort Study were included in the analysis. Multivariable linear
regression was used to investigate whether HIV was independently associated with
aortic stiffness, adjusting for traditional cardiovascular risk factors. RESULTS:
Study groups were comparable in demographics; smoking and hypertension were more
prevalent in HIV-infected participants. PWV was higher in the HIV-infected group
(7.9 vs. 7.7 m/s, P = 0.004). After adjustment for mean arterial pressure, age,
gender, and smoking, HIV status was not significantly associated with aortic
stiffness. In HIV-infected participants, having a nadir CD4 T-cell count <=100
cells per cubic millimeter was independently associated with a higher PWV.
CONCLUSIONS: The increased aortic stiffness in HIV-infected participants was
largely explained by a higher prevalence of traditional cardiovascular risk
factors, particularly smoking. Although HIV itself was not independently
associated with higher aortic stiffness, a prior greater degree of
immunodeficiency was. This suggests a detrimental effect of immunodeficiency on
the aortic wall, possibly mediated by inflammation.
PMID- 27513573
TI - Barriers to Viral Suppression Among Female Sex Workers: Role of Structural and
Intimate Partner Dynamics.
AB - OBJECTIVE: Despite global evidence that sex workers (SWs) are disproportionately
impacted by HIV, data on HIV treatment outcomes among SWs living with HIV remains
sparse. This study examined the correlates of undetectable plasma viral load
(pVL) among street- and off-street SWs living with HIV and on antiretroviral
therapy (ART) in Metro Vancouver, Canada. METHODS: Analyses drew on data (2010
2014) from a longitudinal cohort of SWs (An Evaluation of Sex Workers Health
Access) and confidential linkages with the Drug Treatment Program (DTP) data on
ART dispensation and outcomes. Bivariate and multivariable generalized linear
mixed-effects models were used to identify longitudinal correlates of
undetectable pVL (<50 copies/mL). RESULTS: Of the 72 SWs living with HIV who had
ever used ART, 38.9% had an undetectable pVL at baseline. Although 84.7% had
undetectable pVL at least once over the study period, 18.1% exhibited sustained
undetectable pVL. In multivariable generalized linear mixed-effects model
analyses, >=95% pharmacy refill adherence (adjusted odds ratio (AOR) = 4.21; 95%
confidence interval (CI) 2.16 to 8.19) and length of time since diagnosis (AOR =
1.06; 95% CI: 1.00 to 1.13) were positively correlated with undetectable pVL.
Having an intimate male partner (AOR = 0.35; 95% CI: 0.16 to 0.78) and being
homelessness were negatively correlated with undetectable pVL (AOR = 0.22; 95%
CI: 0.10 to 0.47). DISCUSSION/CONCLUSIONS: There is a need to more closely
consider the social and structural contexts that shape SWs' experiences on ART
and impact treatment outcomes, including the gendered power dynamics within
intimate partnerships. Future research on HIV care among SWs is urgently needed,
alongside structural and community-led interventions to support SWs' access to
and retention in care.
PMID- 27513574
TI - Association between Work-Related Stress and Risk for Type 2 Diabetes: A
Systematic Review and Meta-Analysis of Prospective Cohort Studies.
AB - BACKGROUND/OBJECTIVE: The prevalence of type 2 diabetes is increasing rapidly
around the world. Work-related stress is thought to be a major risk factor for
type 2 diabetes; however, this association has not been widely studied, and the
findings that have been reported are inconsistent. Therefore, we conducted a meta
analysis of prospective cohort studies to explore the association between work
related stress and risk for type 2 diabetes. METHODS: A systematic literature
search and manual search limited to articles published in English were performed
to select the prospective cohort studies evaluated the association between work
related stress and risk for type 2 diabetes up to September 2014 from four
electronic databases including PubMed, EMBASE, the Cochrane Library and Web of
Science. A random-effects model was used to estimate the overall risk. RESULTS:
No significant association was found between work-related stress and risk for
type 2 diabetes based on meta-analysis of seven prospective cohort studies
involving 214,086 participants and 5,511 cases (job demands: relative risk 0.94
[95% confidence interval 0.72-1.23]; decision latitude: relative risk 1.16 [0.85
1.58]; job strain: relative risk 1.12 [.0.95-1.32]). However, an association
between work-related stress and risk for type 2 diabetes was observed in women
(job strain: relative risk 1.22 [1.01-1.46]) (P = 0.04). A sensitivity analysis
conducted by excluding one study in each turn yielded similar results. No
publication bias was detected with a funnel plot despite the limited number of
studies included in the analysis. CONCLUSIONS: The results of this meta-analysis
did not confirm a direct association between work-related stress and risk for
type 2 diabetes. In subgroup analyses we found job strain was a risk factor for
type 2 diabetes in women.
PMID- 27513575
TI - Inactivation of SmeSyRy Two-Component Regulatory System Inversely Regulates the
Expression of SmeYZ and SmeDEF Efflux Pumps in Stenotrophomonas maltophilia.
AB - SmeYZ efflux pump is a critical pump responsible for aminoglycosides resistance,
virulence-related characteristics (oxidative stress susceptibility, motility, and
secreted protease activity), and virulence in Stenotrophomonas maltophilia.
However, the regulatory circuit involved in SmeYZ expression is little known. A
two-component regulatory system (TCS), smeRySy, transcribed divergently from the
smeYZ operon is the first candidate to be considered. To assess the role of
SmeRySy in smeYZ expression, the smeRySy isogenic deletion mutant, KJDeltaRSy,
was constructed by gene replacement strategy. Inactivation of smeSyRy correlated
with a higher susceptibility to aminoglycosides concomitant with an increased
resistance to chloramphenicol, ciprofloxacin, tetracycline, and macrolides. To
elucidate the underlying mechanism responsible for the antimicrobials
susceptibility profiles, the SmeRySy regulon was firstly revealed by
transcriptome analysis and further confirmed by quantitative real-time polymerase
chain reaction (qRT-PCR) and promoter transcription fusion constructs assay. The
results demonstrate that inactivation of smeRySy decreased the expression of
SmeYZ pump and increased the expression of SmeDEF pump, which underlies the
DeltasmeSyRy-mediated antimicrobials susceptibility profile. To elucidate the
cognate relationship between SmeSy and SmeRy, a single mutant, KJDeltaRy, was
constructed and the complementation assay of KJDeltaRSy with smeRy were
performed. The results support that SmeSy-SmeRy TCS is responsible for the
regulation of smeYZ operon; whereas SmeSy may be cognate with another
unidentified response regulator for the regulation of smeDEF operon. The impact
of inverse expression of SmeYZ and SmeDEF pumps on physiological functions was
evaluated by mutants construction, H2O2 susceptibility test, swimming, and
secreted protease activity assay. The increased expression of SmeDEF pump in
KJDeltaRSy may compensate, to some extents, the SmeYZ downexpression-mediated
compromise with respect to its role in secreted protease activity.
PMID- 27513576
TI - Estimates of the Direct Effect of Seawater pH on the Survival Rate of Species
Groups in the California Current Ecosystem.
AB - Ocean acidification (OA) has the potential to restructure ecosystems due to
variation in species sensitivity to the projected changes in ocean carbon
chemistry. Ecological models can be forced with scenarios of OA to help
scientists, managers, and other stakeholders understand how ecosystems might
change. We present a novel methodology for developing estimates of species
sensitivity to OA that are regionally specific, and applied the method to the
California Current ecosystem. To do so, we built a database of all published
literature on the sensitivity of temperate species to decreased pH. This database
contains 393 papers on 285 species and 89 multi-species groups from temperate
waters around the world. Research on urchins and oysters and on adult life stages
dominates the literature. Almost a third of the temperate species studied to date
occur in the California Current. However, most laboratory experiments use control
pH conditions that are too high to represent average current chemistry conditions
in the portion of the California Current water column where the majority of the
species live. We developed estimates of sensitivity to OA for functional groups
in the ecosystem, which can represent single species or taxonomically diverse
groups of hundreds of species. We based these estimates on the amount of
available evidence derived from published studies on species sensitivity, how
well this evidence could inform species sensitivity in the California Current
ecosystem, and the agreement of the available evidence for a species/species
group. This approach is similar to that taken by the Intergovernmental Panel on
Climate Change to characterize certainty when summarizing scientific findings.
Most functional groups (26 of 34) responded negatively to OA conditions, but when
uncertainty in sensitivity was considered, only 11 groups had relationships that
were consistently negative. Thus, incorporating certainty about the sensitivity
of species and functional groups to OA is an important part of developing robust
scenarios for ecosystem projections.
PMID- 27513577
TI - Workplace Health Promotion and Mental Health: Three-Year Findings from Partnering
Healthy@Work.
AB - This study aimed to investigate the association between mental health and
comprehensive workplace health promotion (WHP) delivered to an entire state
public service workforce (~28,000 employees) over a three-year period. Government
departments in a state public service were supported to design and deliver a
comprehensive, multi-component health promotion program, Healthy@Work, which
targeted modifiable health risks including unhealthy lifestyles and stress.
Repeated cross-sectional surveys compared self-reported psychological distress
(Kessler-10; K10) at commencement (N = 3406) and after 3 years (N = 3228). WHP
availability and participation over time was assessed, and associations between
the K10 and exposure to programs estimated. Analyses were repeated for a cohort
subgroup (N = 580). Data were weighted for non-response. Participation in any
mental health and lifestyle programs approximately doubled after 3 years. Both
male and female employees with poorer mental health participated more often over
time. Women's psychological distress decreased over time but this change was only
partially attributable to participation in WHP, and only to lifestyle
interventions. Average psychological distress did not change over time for men.
Unexpectedly, program components directly targeting mental health were not
associated with distress for either men or women. Cohort results corroborated
findings. Healthy@Work was successful in increasing participation across a range
of program types, including for men and women with poorer mental health. A small
positive association of participation in lifestyle programs with mental health
was observed for women but not men. The lack of association of mental health
programs may have reflected program quality, its universality of application or
other contextual factors.
PMID- 27513578
TI - Clinicians and clients disagree: Five implications for clinical science.
AB - Recent findings highlight the limited agreement between diagnostic ratings
provided by practicing clinicians and the self-report and interview methods
typically employed in research settings. Such discrepancies between the diagnoses
assigned in research and applied settings greatly complicate the translation of
empirical findings into practice. This review highlights these disagreements,
offers explanations for these observed differences, and provides 5 implications
for research. Specifically, we provide evidence that, despite criticisms, self
reported psychopathology may be at least as valid as clinicians' unstructured
diagnoses. Further, we highlight the need for research that provides clinicians
with the most valid tools, including those that focus on dimensional constructs,
rather than diagnostic categories. In addition, we recommend that adult
psychopathology research incorporate methodologies from general personality for
unraveling informant discrepancies. We highlight recent work that has provided
valuable tools for incorporating metaperception-the extent to which one is aware
of how they are perceived by others-for contextualizing these differences. We
also underscore the utility of emerging technologies that provide rich data, such
as ambulatory assessment, for overcoming the criterion problem. Finally, we
recommend that advances in combining data from multiple sources from the
childhood psychopathology literature, such as examining the extent to which
discrepancies themselves might aid in diagnosis, be incorporated into adult
psychopathology research. In sum, we hope that these implications inspire
research that improves the science of diagnostic assessment in a way that might
ultimately improve practice. (PsycINFO Database Record
PMID- 27513579
TI - DHA but Not EPA Emulsions Preserve Neurological and Mitochondrial Function after
Brain Hypoxia-Ischemia in Neonatal Mice.
AB - BACKGROUND AND PURPOSE: Treatment with triglyceride emulsions of docosahexaenoic
acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain
injury. The mechanism of this neuroprotection remains unclear. We hypothesized
that administration of tri-DHA enriches HI-brains with DHA/DHA metabolites. This
reduces Ca2+-induced mitochondrial membrane permeabilization and attenuates brain
injury. METHODS: 10-day-old C57BL/6J mice following HI-brain injury received tri
DHA, tri-EPA or vehicle. At 4-5 hours of reperfusion, mitochondrial fatty acid
composition and Ca2+ buffering capacity were analyzed. At 24 hours and at 8-9
weeks of recovery, oxidative injury, neurofunctional and neuropathological
outcomes were evaluated. In vitro, hyperoxia-induced mitochondrial generation of
reactive oxygen species (ROS) and Ca2+ buffering capacity were measured in the
presence or absence of DHA or EPA. RESULTS: Only post-treatment with tri-DHA
reduced oxidative damage and improved short- and long-term neurological outcomes.
This was associated with increased content of DHA in brain mitochondria and DHA
derived bioactive metabolites in cerebral tissue. After tri-DHA administration HI
mitochondria were resistant to Ca2+-induced membrane permeabilization. In vitro,
hyperoxia increased mitochondrial ROS production and reduced Ca2+ buffering
capacity; DHA, but not EPA, significantly attenuated these effects of hyperoxia.
CONCLUSIONS: Post-treatment with tri-DHA resulted in significant accumulation of
DHA and DHA derived bioactive metabolites in the HI-brain. This was associated
with improved mitochondrial tolerance to Ca2+-induced permeabilization, reduced
oxidative brain injury and permanent neuroprotection. Interaction of DHA with
mitochondria alters ROS release and improves Ca2+ buffering capacity. This may
account for neuroprotective action of post-HI administration of tri-DHA.
PMID- 27513580
TI - Multivitamin Use and Serum Vitamin B12 Concentrations in Older-Adult Metformin
Users in REGARDS, 2003-2007.
AB - Metformin, an insulin-sensitizing drug, is a first line treatment for type 2
diabetes. Long-term use of metformin has been associated with subsequent
reductions in vitamin B12 concentrations. The objective of our study was to
determine whether metformin use is associated with lower serum vitamin B12
concentrations in older adults, and whether concurrent use of multivitamins
modifies this association. We examined 2,510 participants aged 50 years and over,
participating in the national population-based Reasons for Geographic And Racial
Differences in Stroke (REGARDS) Study. Multivariable linear and logistic
regression models were used to assess associations between multivitamin use and
serum vitamin B12 concentrations. We estimated adjusted odds ratios (aOR)s and
confidence intervals (CI)s. Results were stratified by three metformin/diabetes
sub-groups: 1) participants with diabetes who were metformin users; 2)
participants with diabetes who were not metformin users; and 3) participants
without diabetes. We found that diabetic metformin users had significantly lower
geometric mean serum B12 concentrations (409 pmol/L) than the group with diabetes
not taking metformin (485 pmol/L; P<0.01), and the group without diabetes (445
pmol/L; P = 0.02). The geometric mean serum B12 concentrations were greater for
multivitamin users (509 pmol/L) compared to those who did not use multivitamins
(376 pmol/L; p<0.01). Among the participants with diabetes who were on metformin
therapy, multivitamin use was associated with geometric mean serum vitamin B12
concentrations that were 50% (or 161 pmol/L) higher, compared to those not using
multivitamins. Among metformin users, multivitamin use was associated with lower
prevalence of combined low and borderline vitamin B12 concentrations (aOR = 0.14;
95% CI = 0.04, 0.54) compared to those not using multivitamins. In conclusion,
metformin use was associated with lower geometric mean serum vitamin B12
concentrations among diabetic older adults compared to their counterparts.
Concurrent multivitamin use may potentially protect against low or borderline
vitamin B12 concentrations in long-term metformin users. Additional research is
needed to further examine this association as low or borderline vitamin B12
concentrations can be preventable, or treatable if detected at an early stage, in
long-term metformin users.
PMID- 27513581
TI - The Profile and Bioaccessibility of Phenolic Compounds in Cereals Influenced by
Improved Extrusion Cooking Treatment.
AB - The aim of this study was to investigate the effect of Improved Extrusion Cooking
Treatment (IECT) on the phenolics and its bioaccessibility in cereals,
represented by brown rice, wheat, and oat. Data showed that total phenolic
content and total antioxidant activity in free form were significantly decreased,
while the bound form was increased after IECT. After IECT, the total free
phenolic acids of brown rice and wheat were significantly decreased by 5.88% and
45.66%, respectively, while the total bound phenolic acids of brown rice, wheat,
and oat were significantly increased by 6.45%, 8.78%, and 9.10%, respectively.
Brown rice provided the most bioaccessible phenolics and antioxidant compounds,
followed by oat and wheat. IECT significantly decreased the bioaccessible
phenolics of brown rice and oat by 31.09% and 30.95%, while it had minimal effect
on the bioaccessible phenolics of wheat. These results showed that IECT greatly
affected the phenolics and its bioaccessibiltiy of cereals, with the effect
depending on cereal matrix and the sensitivity of free and bound phenolics.
Furthermore, bioaccessible phenolic acids of raw and processed cereals were
considerably low, and it slightly contributed to the bioaccessible phenolics.
PMID- 27513583
TI - Preface.
PMID- 27513582
TI - Insights into the Conformation of the Membrane Proximal Regions Critical to the
Trimerization of the HIV-1 gp41 Ectodomain Bound to Dodecyl Phosphocholine
Micelles.
AB - The transitioning of the ectodomain of gp41 from a pre-hairpin to a six-helix
bundle conformation is a crucial aspect of virus-cell fusion. To gain insight
into the intermediary steps of the fusion process we have studied the pH and
dodecyl phosphocholine (DPC) micelle dependent trimer association of gp41 by
systematic deletion analysis of an optimized construct termed 17-172 (residues
528 to 683 of Env) that spans the fusion peptide proximal region (FPPR) to the
membrane proximal external region (MPER) of gp41, by sedimentation velocity and
double electron-electron resonance (DEER) EPR spectroscopy. Trimerization at pH 7
requires the presence of both the FPPR and MPER regions. However, at pH 4, the
protein completely dissociates to monomers. DEER measurements reveal a partial
fraying of the C-terminal MPER residues in the 17-172 trimer while the other
regions, including the FPPR, remain compact. In accordance, truncating nine C
terminal MPER residues (675-683) in the 17-172 construct does not shift the
trimer-monomer equilibrium significantly. Thus, in the context of the gp41
ectodomain spanning residues 17-172, trimerization is clearly dependent on FPPR
and MPER regions even when the terminal residues of MPER unravel. The antibody
Z13e1, which spans both the 2F5 and 4E10 epitopes in MPER, binds to 17-172 with a
Kd of 1 +/- 0.12 MUM. Accordingly, individual antibodies 2F5 and 4E10 also
recognize the 17-172 trimer/DPC complex. We propose that binding of the C
terminal residues of MPER to the surface of the DPC micelles models a correct
positioning of the trimeric transmembrane domain anchored in the viral membrane.
PMID- 27513584
TI - Augmenting SRIs for Obsessive-Compulsive Disorder: Patient Preference for
Risperidone Does Not Limit Effectiveness of Exposure and Ritual Prevention.
PMID- 27513585
TI - Ingenol Mebutate Treatment in a Patient with Gorlin Syndrome.
AB - BACKGROUND: Gorlin syndrome, also known as the basal cell nevus syndrome (OMIM
#109400), is a rare autosomal-dominant genetic disease. The disease, which shows
mutation of the patched receptor gene (PTCH1) of the sonic hedgehog pathway, is
characterized by developing multiple basal cell carcinomas (BCCs) in adolescent
patients. Other clinical features include mandibular keratocysts, palmar and
plantar pits, skeletal abnormalities and malformations central nervous system and
genital tract. Gorlin-Goltz patients need multidisciplinary medical care and
follow-up as well as genetic counseling if the patients want to have children.
The treatment of multiple BCCs includes conventional surgery, micrographic Mohs
surgery, cryotherapy, laser ablation, photodynamic therapy, imiquimod 5% cream, 5
fluorouracil cream as well as the sonic hedgehog pathway inhibitor vismodegib.
CASE REPORT: We report the case of a 30-year-old woman seen in our dermatological
department since 2003. All the above-mentioned modalities had been employed for
her numerous BCCs. The patient grew wary of the surgical procedures because of
the countless scars. We successfully treated multiple BCCs with ingenol mebutate
without post-inflammatory scarring. At 8-month follow-up, the patient shows no
recurrence of the treated lesions. CONCLUSION: Ingenol mebutate can be used to
treat (superficial) BCCs in patients with Gorlin-Goltz syndrome as an additional
modality. Close clinical follow-up is recommended.
PMID- 27513586
TI - The Effect of Problem-Based Learning on Improvement of the Medical Educational
Environment: A Systematic Review and Meta-Analysis.
AB - OBJECTIVES: The aim of this study was to evaluate the effect of problem-based
learning on improving the medical educational environment. MATERIALS AND METHODS:
All relevant studies on problem-based learning and the medical educational
environment were searched for in PubMed, the Education Resources Information
Center (ERIC) catalogue, Google Scholar, China National Knowledge Infrastructure
(CNKI) and WanFang Data (WF) databases for material dating from 1969 to May 2015
without any language limitation. Six randomized controlled trials of problem
based learning compared to traditional lecture-based learning were included. The
Cochrane risk of bias tool was used to assess the quality of the included
studies. Review Manager (Revman) version 5.3 software was used for data analysis.
The effect size of the improvement on the medical educational environment was
calculated as the mean difference and 95% confidence interval. Heterogeneity was
evaluated with Cochrane's chi2 test and I2. Publication bias was assessed by
funnel plot, Begg's rank correlation test, and Egg's linear regression test.
RESULTS: The six included studies were at low risk of bias in all domains except
for three that were at high risk of bias in the domain of allocation concealment.
The pooled effect size showed that problem-based learning was better than lecture
based learning in improving the medical educational environment, as measured by
the Dundee Ready Education Environment Measure (DREEM), with statistically
significant differences. No significant publication bias was observed. The
sensitivity analysis showed that the result was reliable. CONCLUSIONS: This study
showed that problem-based learning was able to improve the medical educational
environment as measured by DREEM. However, further studies with larger sample
sizes and high-quality data are needed.
PMID- 27513587
TI - Targeting cancer cells via tumor-homing peptide CREKA functional PEG
nanoparticles.
AB - Targeting cell microenvironment via nano-particle based therapies holds great
promise for the treatment of various diseases. One of the main challenges in
targeted delivery of nanoparticles for cancer therapy is the reduced localization
of delivery vehicles to the tumor site. The therapeutic efficacy of drugs can be
improved by recruiting delivery vehicles towards specific region of tumorigenesis
in the body. Here, we demonstrate an effective approach in creating PEG particles
via water-in-water emulsion technique with a tumor-homing peptide CREKA
functionalization. The CREKA conjugated hydrogel nanoparticles were found to be
more effective at inducing Doxorubicin (DOX)-mediated apoptosis compared to that
of particles conjugated with laminin peptide IKVAV. Fluorescence intensity
analysis on confocal micrographs suggested significantly higher cellular uptake
of CREKA conjugated PEG particles than internalization of nanoparticles in other
groups. We observed that fibrin binding ability of PEG particles could be
increased up to 94% through CREKA conjugation. Our results suggest the
possibility of cancer cell targeting via CREKA-functional PEG nanoparticles.
PMID- 27513588
TI - PLGA nanoparticles from nano-emulsion templating as imaging agents: Versatile
technology to obtain nanoparticles loaded with fluorescent dyes.
AB - The interest in polymeric nanoparticles as imaging systems for biomedical
applications has increased notably in the last decades. In this work, PLGA
nanoparticles, prepared from nano-emulsion templating, have been used to prepare
novel fluorescent imaging agents. Two model fluorescent dyes were chosen and
dissolved in the oil phase of the nano-emulsions together with PLGA. Nano
emulsions were prepared by the phase inversion composition (PIC) low-energy
method. Fluorescent dye-loaded nanoparticles were obtained by solvent evaporation
of nano-emulsion templates. PLGA nanoparticles loaded with the fluorescent dyes
showed hydrodynamic radii lower than 40nm; markedly lower than those reported in
previous studies. The small nanoparticle size was attributed to the nano
emulsification strategy used. PLGA nanoparticles showed negative surface charge
and enough stability to be used for biomedical imaging purposes. Encapsulation
efficiencies were higher than 99%, which was also attributed to the nano
emulsification approach as well as to the low solubility of the dyes in the
aqueous component. Release kinetics of both fluorescent dyes from the
nanoparticle dispersions was pH-independent and sustained. These results indicate
that the dyes could remain encapsulated enough time to reach any organ and that
the decrease of the pH produced during cell internalization by the endocytic
route would not affect their release. Therefore, it can be assumed that these
nanoparticles are appropriate as systemic imaging agents. In addition, in vitro
toxicity tests showed that nanoparticles are non-cytotoxic. Consequently, it can
be concluded that the preparation of PLGA nanoparticles from nano-emulsion
templating represents a very versatile technology that enables obtaining
biocompatible, biodegradable and safe imaging agents suitable for biomedical
purposes.
PMID- 27513589
TI - Laparoscopic Treatment of a Retroduodenopancreatic Endometriotic Cyst Observed
Postpartum.
AB - Endometriosis occurs in 5%-10% of fertile women, usually in the pelvic region,
such as the ovaries, uterine ligaments, pelvic peritoneum, and rectovaginal
septum. A mesenteric endometriotic cyst is an exceptional observation and
difficult to diagnose preoperatively. We report a case of a large mesenteric
endometriotic cyst treated by laparoscopy. A 21-year-old Caucasian woman was
admitted as an emergency to our Academic Hospital on the 30th day postpartum for
abdominal pain and a palpable epigastric mass. A CT scan revealed a mass
measuring 7.5 * 5.5 cm showing a fluid content, located below the pancreas. A
preoperative diagnosis of mesenteric cyst was made and confirmed by MRI. A
dissection of the mass from the inferior vena cava, pancreas, and duodenum was
achieved by a laparoscopic approach. During the blunt dissection, avoiding any
spillage, the cyst was aspirated to preserve a safe cleavage plane with the lower
third of the duodenum showing tenacious adhesions to the mass. Histology revealed
an endometriotic cyst of the mesenterium. To our knowledge, this is the first
case reported in the literature of laparoscopic treatment of a
retroduodenopancreatic endometriotic cyst observed postpartum. In dedicated
centers, laparoscopic management could be the gold standard.
PMID- 27513590
TI - Alternative Estimates of Lifetime Prevalence Of Abortion from Indirect Survey
Questioning Methods.
PMID- 27513591
TI - Isolation as a strategy for controlling the transmission of hepatitis C virus
(HCV) infection in haemodialysis units.
AB - BACKGROUND: The hepatitis C virus (HCV) infection affects about 2% of the world's
population and can cause chronic liver infection and persistent long-term
sequelae such as cirrhosis and liver cancer.The prevalence of HCV infection among
people on haemodialysis is often higher than the general population. The virus is
easily transmitted parenterally, and blood transfusions have previously played a
significant role in transmission; however, erythropoietin therapy has reduced the
need for transfusions, and coupled with improved screening of donated blood, has
significantly decreased transmission by transfusion. Although control of hospital
acquired infection has improved with the advent of biosafety measures, stopping
HCV transmission in haemodialysis units remains challenging.Isolating people
infected with HCV involves physical separation from others to limit direct or
indirect transmission and includes a number of strategies during dialysis. The
evidence for isolating people infected with HCV during haemodialysis is sparse
with some inconsistencies. OBJECTIVES: To evaluate the benefits and harms of
isolation of HCV-infected patients during haemodialysis on the transmission of
HCV to other patients. SEARCH METHODS: We searched the Cochrane Kidney and
Transplant Specialised Register to 26 November 2015 through contact with the
Information Specialist using search terms relevant to this review. We also
searched the Latin American and Caribbean Health Sciences Literature Database
(LILACS) (1982 to 2015), Web of Science Conference Proceedings Citation Index
Science (CPCI-S, 1990 to 2015), ProQuest Dissertations & Theses Database (1990 to
2015), and Open Grey (1990 to 2015). SELECTION CRITERIA: We included randomised
controlled trials (RCTs), quasi-RCTs and cluster RCTs evaluating the clinical
benefits and harms of isolating HCV-infected patients during haemodialysis on the
transmission of HCV to other patients. We considered incidence of dialysis
acquired HCV infection, all-cause mortality, and adverse effects associated with
isolation as the primary outcomes. DATA COLLECTION AND ANALYSIS: Summary
estimates of effect were obtained using a random-effects model, and results were
expressed as risk ratios (RR) and their 95% confidence intervals (CI) for
dichotomous outcomes, and mean difference (MD) or standardised mean difference
(SMD) and 95% CI for continuous outcomes. MAIN RESULTS: Only one study, which
included 12 centres was identified: four centres used dedicated haemodialysis
machines for HCV-infected patients and eight centres used non-dedicated machines.
The total number of patients enrolled was 593. One centre was excluded after
randomisation. Random sequence generation was not described and allocation
concealment was not performed. Participants and personnel were not blinded and
blinding of outcome assessors was not reported. Only 74.5% of the patients were
followed for 9 months; and 47.3% were followed for an additional 9 months. The
authors only reported one outcome, measuring the difference in the incidence of
HCV in both groups. The authors did not consider the exposure time, to determine
the adjusted rate of seroconversion risk/patient-year. The study reported that
the incidence of HCV infection during the first follow-up period (9 months) was
1.6% in the dedicated group, and 4.7% in the non-dedicated one (446 patients
analysed out of 593 randomised; RR 0.34, 95% CI 0.11 to 1.07). During the second
follow-up period (18 months) the incidence was 1.3% in the dedicated group and
5.8% in the control (281 patients analysed out of 593 randomised; RR 0.22, 95% CI
0.05 to 1.02). Therefore, we found no differences in terms of the number of
participants developing HCV infection when comparing the dedicated group with the
usual care. Moreover, the evidence was of very low quality, which means that we
have very little confidence in the effect estimate. AUTHORS' CONCLUSIONS: The
benefits and harms of isolation of HCV-infected patients during haemodialysis on
the transmission of HCV to other patients are uncertain. Evidence from one short
duration cluster-randomised study with a high risk of bias did not find
differences in terms of the number of participants developing HCV infection when
comparing the use of dedicated haemodialysis machines for HCV infected patients
with the use of non-dedicated machines.
PMID- 27513592
TI - DNA Translocation through Nanopores at Physiological Ionic Strengths Requires
Precise Nanoscale Engineering.
AB - Many important processes in biology involve the translocation of a biopolymer
through a nanometer-scale pore. Moreover, the electrophoretic transport of DNA
across nanopores is under intense investigation for single-molecule DNA
sequencing and analysis. Here, we show that the precise patterning of the ClyA
biological nanopore with positive charges is crucial to observe the
electrophoretic translocation of DNA at physiological ionic strength.
Surprisingly, the strongly electronegative 3.3 nm internal constriction of the
nanopore did not require modifications. Further, DNA translocation could only be
observed from the wide entry of the nanopore. Our results suggest that the
engineered positive charges are important to align the DNA in order to overcome
the entropic and electrostatic barriers for DNA translocation through the narrow
constriction. Finally, the dependencies of nucleic acid translocations on the
Debye length of the solution are consistent with a physical model where the
capture of double-stranded DNA is diffusion-limited while the capture of single
stranded DNA is reaction-limited.
PMID- 27513593
TI - Cultural buffering as a protective factor against electronic cigarette use among
Hispanic emergency department patients.
AB - INTRODUCTION: Hispanics in the U.S. historically use tobacco at lower rates than
other racial and ethnic groups. Cultural buffering, the process by which aspects
of traditional Hispanic culture delay the adoption of unhealthy behaviors, is
believed to be a protective factor against tobacco use. Electronic cigarettes (e
cigarettes) are a new tobacco product that have not been extensively studied, and
it is unknown if cultural factors that protect against tobacco use will buffer
against e-cigarette use among the Hispanic population. METHODS: This cross
sectional study was conducted at the emergency department (ED) in a safety-net
hospital in 2014. Patients visiting the ED participated in a survey assessing
demographics and substance use. Cultural buffering was operationalized as
participants' primary language spoken at home. Multivariate logistic regression
and generalized estimating equations examined the association between Hispanic
cultural buffering and e-cigarette ever-use. RESULTS: Of the 1476 Hispanic ED
patients (age: 46.6M+/-14.5SD, 49.3% male), 7.6% reported e-cigarette ever-use
and 11.1% reported current combustible cigarette use. In adjusted models, Spanish
speakers were half as likely to report e-cigarette ever-use (O.R.: 0.54, 95%
C.I.: 0.34-0.84, p=0.007), compared with English speakers. Combustible cigarette
use remained the most significant factor associated with e-cigarette ever-use
(O.R.: 9.28, 95% C.I.:7.44-11.56, p<0.001). In higher-income neighborhoods,
English speakers reported e-cigarette ever-use at higher rates than Spanish
speakers (28.2% vs. 5.9%, p<0.001). CONCLUSIONS: Cultural buffering was
protective against e-cigarette ever-use, especially in higher-income
neighborhoods. These results support research on culturally-sensitive prevention
programs for new and emerging tobacco products in Hispanic communities.
PMID- 27513594
TI - Stages of physical dependence in New Zealand smokers: Prevalence and correlates.
AB - BACKGROUND: Physically dependent smokers experience symptoms of wanting, craving
or needing to smoke when too much time has passed since the last cigarette. There
is interest in whether wanting, craving and needing represent variations in the
intensity of a single physiological parameter or whether multiple physiological
processes may be involved in the developmental progression of physical
dependence. AIM: Our aim was to determine how a population of cigarette smokers
is distributed across the wanting, craving and needing stages of physical
dependence. METHODS: A nationwide survey of 2594 New Zealanders aged 15years and
over was conducted in 2014. The stage of physical dependence was assessed using
the Levels of Physical Dependence measure. Ordinal logistic regression analysis
was used to assess relations between physical dependence and other variables.
RESULTS: Among 590 current smokers (weighted 16.2% of the sample), 22.3% had no
physical dependence, 23.5% were in the Wanting stage, 14.4% in the Craving stage,
and 39.8% in the Needing stage. The stage of physical dependence was predicted by
daily cigarette consumption, and the time to first cigarette, but not by age,
gender, ethnicity or socioeconomic status. CONCLUSION: Fewer individuals were in
the craving stage than either the wanting or needing stages. The resulting
inverted U-shaped curve with concentrations at either extreme is difficult to
explain as a variation of a single biological parameter. The data support an
interpretation that progression through the stages of wanting, craving and
needing may involve more than one physiological process. WHAT THIS RESEARCH ADDS:
Physical dependence to tobacco develops through a characteristic sequence of
wanting, craving and needing which correspond to changes in addiction pathways in
the brain. It is important to neuroscience research to determine if the
development of physical dependence involves changes in a single brain process, or
multiple processes. Our data suggests that more than one physiologic process is
involved in the progression of physical dependence.
PMID- 27513596
TI - Gene Drives: Biological Shield or Ecological Menace?
PMID- 27513597
TI - Antioxidative Theranostic Iron Oxide Nanoparticles toward Brain Tumors Imaging
and ROS Production.
AB - Gliomas are the most common primary brain tumor in humans. To date, the only
treatment of care consists of surgical removal of the tumor bulk, irradiation,
and chemotherapy, finally resulting in a very poor prognosis due to the lack of
efficiency in diagnostics. In this context, nanomedicine combining both
diagnostic and magnetic resonance imaging (MRI) and therapeutic applications is a
relevant strategy referred to theranostic. Magnetic nanoparticles (NP) are
excellent MRI contrast agents because of their large magnetic moment, which
induces high transverse relaxivity (r2) characteristic and increased
susceptibility effect (T2*). NP can be also used for drug delivery by coating
their surface with therapeutic molecules. Preliminary in vitro studies show the
high potential of caffeic acid (CA), a natural polyphenol, as a promising
anticancer drug due to its antioxidant, anti-inflammatory, and antimetastatic
properties. In this study, the antioxidative properties of iron oxide NP
functionalized with caffeic acid (gammaFe2O3@CA NP) are investigated in vitro on
U87-MG brain cancer cell lines. After intravenous injection of these NP in mice
bearing a U87 glioblastoma, a negative contrast enhancement was specifically
observed on 11.7 T MRI images in cancerous tissue, demonstrating a passive
targeting of the tumor with these nanoplatforms.
PMID- 27513598
TI - Adherence to insulin therapeutic regimens in patients with type 1 diabetes. A
nationwide survey in Brazil.
AB - AIMS: Determine the relationship between self-reported adherence to insulin
therapeutic regimens in Brazilian patients with type 1 diabetes and demographic,
clinical data, glycemic control and cardiovascular risk factors. METHODS: This
was a cross-sectional, multicenter study conducted between August 2011 and August
2014 in 10 Brazilian cities. Data were obtained from 1698 patients, aged 30.0+/
11.90years (55.5% females, 53.6% Caucasians) with a diabetes duration of 15.4+/
1.9years. Adherence was evaluated using an adapted 4-item Morisky Medication
Scale (MMAS) questionnaire. RESULTS: A total of 166 (9.8%), 717 (42.2%) and 815
(48.0%) of the patients reported maximal (group 0), moderate (group 1) and
minimal (group 2) adherence to their insulin therapeutic regimen, respectively. A
significant difference in HbA1c was observed in patients from group 2, 9.2+/-2.2%
(77+/-25mmol/mol) compared to group 1, 8.9+/-2.0% (74+/-22mmol/mol) and group 0,
8.6+/-1.9% (71+/-21mmol/mol) (p=0.003). A multivariate logistic analysis revealed
that the significant independent variables related to higher insulin therapeutic
regimen adherence were older age, higher adherence to diet, lower rate of self
reported hypoglycemia in the last month, low economic status and living in the
Southeast region. Insulin therapeutic regimens, number of daily insulin
injections, self-monitoring of blood glucose, gender, ethnicity and
cardiovascular risk factors were not related to adherence. CONCLUSIONS: Most
Brazilian T1D patients did not adhere to their prescribed insulin therapeutic
regimen, according to the MMAS 4-item scale. This tool should be initially used
to identify non-adherent patients and help them overcome the barriers to
adherence to their prescriptions.
PMID- 27513599
TI - Survey of U.S. Organ Procurement Organizations Regarding Pediatric Organ Donor
Management.
AB - OBJECTIVE: To describe the current practice of pediatric organ donor management
in the United States for donors declared dead based upon neurologic criteria. The
study directs particular attention to how pediatric donors are defined, the use
of donor management guidelines, the use of donor management goals, and the
involvement of pediatric critical care or transplantation expertise. DESIGN:
Cross-sectional observational study using a web-based survey and follow-up
telephone interview with respondents from U.S. organ procurement organizations.
The study also incorporated organ procurement organization-specific data on organ
yield for the 4-year period (2010-2013) preceding the study. SETTING: The 58 U.S.
organ procurement organizations. SUBJECTS: Respondents chosen by each organ
procurement organization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All
58 U.S. organ procurement organizations participated in the study. Fifty-two
respondents (90%) indicated that their organ procurement organization
distinguished pediatric from adult donors resulting in 28 unique pediatric
definitions. Thirty-nine organ procurement organizations utilized some form of
written pediatric management guidelines, and 27 (47%) maintained pediatric donor
management goals; compliance was infrequently monitored for both guidelines (28%)
and goals (33%). A pediatric intensivist was always or usually involved in
pediatric donor management at 47 organ procurement organizations (81%);
transplant/organ recovery surgeons were always or usually involved at 12 organ
procurement organizations (21%). There was an increase in the number of organs
transplanted per donor among donors 11-17 years old for organ procurement
organizations that used donor management goals for the duration of the period
studied (p < 0.01). There was also an increase in the ratio of observed/expected
organs transplanted among donors of 0-10 years old for organ procurement
organizations that always or usually consulted a transplant/organ recovery
surgeon (p = 0.02) although this did not reach our threshold for statistical
significance.. CONCLUSIONS: There is little consensus among organ procurement
organizations regarding the definition of "pediatric" during organ donor
management. Most organ procurement organizations employ written pediatric
guidelines and use pediatric intensive care physicians for assistance in managing
these donors. There is a positive association between the use of donor management
goals and organ yield among pediatric donors in the 11- to 17-year age group.
PMID- 27513600
TI - Utilizing a Collaborative Learning Model to Promote Early Extubation Following
Infant Heart Surgery.
AB - OBJECTIVE: To determine whether a collaborative learning strategy-derived
clinical practice guideline can reduce the duration of endotracheal intubation
following infant heart surgery. DESIGN: Prospective and retrospective data
collected from the Pediatric Heart Network in the 12 months pre- and post
clinical practice guideline implementation at the four sites participating in the
collaborative (active sites) compared with data from five Pediatric Heart Network
centers not participating in collaborative learning (control sites). SETTING: Ten
children's hospitals. PATIENTS: Data were collected for infants following two
index operations: 1) repair of isolated coarctation of the aorta (birth to 365 d)
and 2) repair of tetralogy of Fallot (29-365 d). There were 240 subjects eligible
for the clinical practice guideline at active sites and 259 subjects at control
sites. INTERVENTIONS: Development and application of early extubation clinical
practice guideline. MEASUREMENTS AND MAIN RESULTS: After clinical practice
guideline implementation, the rate of early extubation at active sites increased
significantly from 11.7% to 66.9% (p < 0.001) with no increase in reintubation
rate. The median duration of postoperative intubation among active sites
decreased from 21.2 to 4.5 hours (p < 0.001). No statistically significant change
in early extubation rates was found in the control sites 11.7% to 13.7% (p =
0.63). At active sites, clinical practice guideline implementation had no
statistically significant impact on median ICU length of stay (71.9 hr pre- vs
69.2 hr postimplementation; p = 0.29) for the entire cohort. There was a trend
toward shorter ICU length of stay in the tetralogy of Fallot subgroup (71.6 hr
pre- vs 54.2 hr postimplementation, p = 0.068). CONCLUSIONS: A collaborative
learning strategy designed clinical practice guideline significantly increased
the rate of early extubation with no change in the rate of reintubation. The
early extubation clinical practice guideline did not significantly change
postoperative ICU length of stay.
PMID- 27513601
TI - Resection of the ethmoidal crest in sphenopalatine artery surgery.
AB - BACKGROUND: In severe cases of epistaxis, in spite of several procedures
described in the literature for its management, surgical treatment has been
recognized by most authors as 1 of the most effective, especially when it
includes ligation and/or electrocoagulation of the nasal branches of the
sphenopalatine artery. The objective of this study is to determine the importance
of ethmoid crest resection during sphenopalatine artery surgery, in the
management of severe epistaxis. METHODS: We report a double-blinded randomized
clinical trial, in which intervention was the ethmoid crest resection during
electrocoagulation of the sphenopalatine artery. The study participants consisted
of 42 patients with severe epistaxis and indication for surgical treatment,
treated at the Otorhinolaryngology Emergency Room (ORL ER) of Hospital Sao Paulo,
the teaching hospital of the Federal University of Sao Paulo. RESULTS: There was
significant greater exposure of the arterial branch after removal of the
ethmoidal crest (p = 0.009). The rate of bleeding within 48 hours of the
procedure was significantly lower in the crest removal group. CONCLUSION:
Resection of the ethmoid crest during sphenopalatine surgery proved to be
feasible without additional risks, including promoting decrease in the overall
surgical time. It provided better exposure of arterial branches of the
sphenopalatine foramen, leading to a lower rebleeding rate within 48 hours.
PMID- 27513602
TI - Variations in attack behaviours between Glossina palpalis gambiensis and G.
tachinoides in a gallery forest suggest host specificity.
AB - Tsetse flies Glossina palpalis gambiensis and G. tachinoides are among the major
vectors of sleeping sickness (Human African Trypanosomiasis-HAT) and nagana
(African Animal Trypanosomiasis - AAT) in West Africa. Both riparian species
occur sympatrically in gallery forests of south west Burkina Faso, but little is
known of their interspecies relationships although different authors think there
may be some competition between them. The aim of this study was to check if
sympatric species have different strategies when approaching a host. A man placed
in a sticky cube (1 m * 1 m * 1 m) and a sticky black-blue-black target (1 m * 1
m) were used to capture tsetse along the Comoe river banks in a Latin Square
design. The number and the height at which tsetse were caught by each capture
method were recorded according to species and sex. Glossina p. gambiensis was
more attracted to human bait than to the target, but both species were captured
at a significantly higher height on the target compared with the human bait (P <
0.05). No significant difference in heights was found between G. tachinoides and
G. p. gambiensis captured on targets (33 and 35 cm, respectively, P > 0.05).
However, catches on human bait showed a significant difference in height between
G. tachinoides and G. p. gambiensis (22.5 and 30.6 cm, respectively, P < 0.001).
This study showed that these sympatric species had different attack behaviours to
humans, which is not the case with the target. The implications of these findings
are discussed.
PMID- 27513603
TI - Stakeholders' views of recurrent sore throat, tonsillitis and their management: a
qualitative interview study for the NAtional Trial of Tonsillectomy IN Adults
(NATTINA Part 1).
AB - OBJECTIVES: To determine the impact of recurrent sore throats and tonsillitis in
adults and stakeholder views of treatment pathways. DESIGN: Qualitative
semistructured interview design reporting novel data from a feasibility study for
a UK national trial of tonsillectomy in adults. SETTING: Nine study sites linked
to ear, nose and throat departments in National Health Service hospitals located
across the United Kingdom. PARTICIPANTS: Fifteen patients, 11 general
practitioners and 22 ear, nose and throat staff consented to in-depth interviews,
which were analysed using a framework analysis approach. MAIN OUTCOME MEASURES:
Views of stakeholder groups. RESULTS: Recurrent sore throats were reported to
severely impact patients' family, work and social life. Ear, nose and throat
staff stated that patients faced increasing barriers to secondary care service
access. General practitioners were under pressure to reduce 'limited clinical
value' surgical procedures. CONCLUSIONS: The findings from this study suggest
that there is a disconnect between the attitudes of the stakeholders and the
reality of recurrent sore throat, tonsillectomy procedures and service provision.
More evidence for the role of tonsillectomy is needed from randomised controlled
trials to determine whether it should continue to be ranked as a procedure of
limited clinical effectiveness.
PMID- 27513605
TI - Gold-Induced Fibril Growth: The Mechanism of Surface-Facilitated Amyloid
Aggregation.
AB - The question of how amyloid fibril formation is influenced by surfaces is crucial
for a detailed understanding of the process in vivo. We applied a combination of
kinetic experiments and molecular dynamics simulations to elucidate how (model)
surfaces influence fibril formation of the amyloid-forming sequences of prion
protein SUP35 and human islet amyloid polypeptide. The kinetic data suggest that
structural reorganization of the initial peptide corona around colloidal gold
nanoparticles is the rate-limiting step. The molecular dynamics simulations
reveal that partial physisorption to the surface results in the formation of
aligned monolayers, which stimulate the formation of parallel, critical
oligomers. The general mechanism implies that the competition between the
underlying peptide-peptide and peptide-surface interactions must strike a balance
to accelerate fibril formation.
PMID- 27513606
TI - Ultrathin Polymer Membranes with Patterned, Micrometric Pores for Organs-on
Chips.
AB - The basal lamina or basement membrane (BM) is a key physiological system that
participates in physicochemical signaling between tissue types. Its formation and
function are essential in tissue maintenance, growth, angiogenesis, disease
progression, and immunology. In vitro models of the BM (e.g., Boyden and
transwell chambers) are common in cell biology and lab-on-a-chip devices where
cells require apical and basolateral polarization. Extravasation, intravasation,
membrane transport of chemokines, cytokines, chemotaxis of cells, and other key
functions are routinely studied in these models. The goal of the present study
was to integrate a semipermeable ultrathin polymer membrane with precisely
positioned pores of 2 MUm diameter in a microfluidic device with apical and
basolateral chambers. We selected poly(l-lactic acid) (PLLA), a transparent
biocompatible polymer, to prepare the semipermeable ultrathin membranes. The
pores were generated by pattern transfer using a three-step method coupling
femtosecond laser machining, polymer replication, and spin coating. Each step of
the fabrication process was characterized by scanning electron microscopy to
investigate reliability of the process and fidelity of pattern transfer. In order
to evaluate the compatibility of the fabrication method with organs-on-a-chip
technology, porous PLLA membranes were embedded in polydimethylsiloxane (PDMS)
microfluidic devices and used to grow human umbilical vein endothelial cells
(HUVECS) on top of the membrane with perfusion through the basolateral chamber.
Viability of cells, optical transparency of membranes and strong adhesion of PLLA
to PDMS were observed, thus confirming the suitability of the prepared membranes
for use in organs-on-a-chip devices.
PMID- 27513607
TI - 3D correlative morphological and elemental characterization of materials at the
deep submicrometre scale.
AB - This paper shows how X-ray computed nanotomography (CNT) can be correlated with
focused ion beam time-of-flight secondary ion mass spectrometry (FIB-TOF-SIMS)
tomography on the same sample to investigate both the morphological and elemental
structure. This methodology is applicable to relatively large specimens with
dimensions of several tens of microns whilst maintaining a high spatial
resolution of the order of 100 nm. However, combining X-ray CNT and FIB-TOF-SIMS
tomography requires innovative sample preparation protocols to allow both
experiments to be conducted on exactly the same sample without chemically or
structurally modifying the sample between measurements. Moreover, dedicated
algorithms have been developed for effective data fusion that is biased with nine
degrees of freedom. This methodology has been tested using a porous and
heterogeneous solid oxide fuel cell (SOFC) that has features varying in size by
three orders of magnitude - from hundreds of nanometre large pores and grains to
tens of micron wide functional layers.
PMID- 27513608
TI - The role of RNase 7 in innate cutaneous defense against Pseudomonas aeruginosa.
AB - The ribonuclease RNase 7 is a major skin-derived human antimicrobial protein
expressed in keratinocytes. Here we show that the gram-negative pathogen
Pseudomonas aeruginosa secretes factor(s) that induced RNase 7 gene and protein
expression in human primary keratinocytes. The metalloprotease inhibitor
marimastat, the epidermal growth factor receptor (EGFR) inhibitor AG1478 and the
EGFR blocking antibody cetuximab significantly attenuated this induction,
indicating an important role of the EGFR for the P. aeruginosa-mediated RNase 7
induction. In line with this, siRNA-mediated downregulation of ADAM17, a
metalloprotease known to proteolytically mediate the release of soluble EGFR
ligands, decreased the P. aeruginosa-mediated RNase 7 induction in keratinocytes.
The impact of the EGFR was also demonstrated in a human 3D skin equivalent where
blockade of the EGFR diminished induction of RNase 7 by P. aeruginosa. Blockade
of Toll-like receptor 5 (TLR5), a pattern recognition receptor (PRR) known to be
activated by P. aeruginosa, only moderately reduced the P. aeruginosa-mediated
RNase 7 induction in keratinocytes. The functional relevance of RNase 7 to
participate in cutaneous defense against P. aeruginosa was demonstrated by
antibodies that neutralized the antimicrobial activity of RNase 7. These
antibodies significantly inhibited the capacity of human stratum corneum skin
extracts to control growth of P. aeruginosa. Taken together, our results indicate
that P. aeruginosa induces the expression of RNase 7 in keratinocytes in an EGFR
dependent manner. Enhanced release of RNase 7 contributes to control cutaneous
growth of P. aeruginosa.
PMID- 27513609
TI - The Impact of Standardized Acuity Assessment and a Fast-Track on Length of Stay
in Obstetric Triage: A Quality Improvement Study.
AB - To prospectively assess the impact of a standardized 5-category Obstetrical
Triage Acuity Scale (OTAS) and a fast-track for lower-acuity patients on patient
flow. Length of stay (LOS) data of women presenting to obstetric triage were
abstracted from the electronic medical record prior to (July 1, 2011, to March
30, 2012) and following OTAS implementation (April 1 to December 31, 2012).
Following computerized simulation modeling, a fast-track for lower acuity women
was implemented (January 1, 2013, to February 28, 2014). Prior to OTAS
implementation (8085 visits), the median LOS was 105 (interquartile range [IQR] =
52-178) minutes. Following OTAS implementation (8131 visits), the median LOS
decreased to 101 (IQR = 49-175) minutes (P = .04). The LOS did not correlate well
with acuity. Simulation modeling predicted that a fast-track for OTAS 4 and 5
patients would reduce the LOS. The LOS for lower-acuity patients in the fast
track decreased to 73 (IQR = 40-140) minutes (P = .005). In addition, the overall
LOS (12 576 visits) decreased to 98 (IQR = 47-172) minutes (6.9% reduction; P <
.001). Standardized assessment of acuity and a fast-track for lower acuity
pregnant women decreased the overall LOS and the LOS of lower-acuity patients.
PMID- 27513610
TI - Hapmnioides A-C, Rearranged Labdane-Type Diterpenoids from the Chinese Liverwort
Haplomitrium mnioides.
AB - Many exceptional labdane-type diterpenoids have been exclusively found in
liverworts, which serve as taxonomic molecules or play important ecological roles
in interactions among organisms. Three unprecedented labdane-type diterpenoids
hapmnioides A (1), B (2), and C (3) formed through cascade rearrangement from the
Chinese liverwort Haplomitrium mnioides are reported. Their structures were
established by comprehensive spectroscopic analysis coupled with single-crystal X
ray diffraction, and their anti-inflammatory activities were also preliminarily
tested.
PMID- 27513611
TI - Unpacking the public stigma of problem gambling: The process of stigma creation
and predictors of social distancing.
AB - Background and aims Public stigma diminishes the health of stigmatized
populations, so it is critical to understand how and why stigma occurs to inform
stigma reduction measures. This study aimed to examine stigmatizing attitudes
held toward people experiencing problem gambling, to examine whether specific
elements co-occur to create this public stigma, and to model explanatory
variables of this public stigma. Methods An online panel of adults from Victoria,
Australia (N = 2,000) was surveyed. Measures were based on a vignette for problem
gambling and included demographics, gambling behavior, perceived dimensions of
problem gambling, stereotyping, social distancing, emotional reactions, and
perceived devaluation and discrimination. A hierarchical linear regression was
conducted. Results People with gambling problems attracted substantial negative
stereotypes, social distancing, emotional reactions, and status
loss/discrimination. These elements were associated with desired social distance,
as was perceived that problem gambling is caused by bad character, and is
perilous, non-recoverable, and disruptive. Level of contact with problem
gambling, gambling involvement, and some demographic variables was significantly
associated with social distance, but they explained little additional variance.
Discussion and conclusions This study contributes to the understanding of how and
why people experiencing gambling problems are stigmatized. Results suggest the
need to increase public contact with such people, avoid perpetuation of
stereotypes in media and public health communications, and reduce devaluing and
discriminating attitudes and behaviors.
PMID- 27513612
TI - Isolated effect of material stiffness on valvular interstitial cell
differentiation.
AB - Previous methods for investigating material stiffness on cell behavior have
focused on the use of substrates with limited ranges of stiffness and/or
fluctuating surface chemistries. Using the co-polymer system of n-octyl
methacrylate crosslinked with diethylene glycol dimethacrylate (DEGDMA/nOM), we
developed a new cell culture platform to analyze the isolated effects of
stiffness independent from changes in surface chemistry. Materials ranging from
25 kPa to 4,700 kPa were fabricated. Surface analysis including goiniometry and X
ray photoelectron spectroscopy (XPS) confirmed consistent surface chemistry
across all formulations examined. The mechanosensitive cell type valvular
interstitial cell (VIC) was cultured DEGDMA/nOM substrates of differing
stiffness. Results indicate that order of magnitude changes in stiffness do not
increase gene expression of VIC alpha-smooth muscle actin (alphaSMA). However,
structural organization of alphaSMA is altered on stiffer substrates,
corresponding with the appearance of the osteoblastic marker osteocalcin and
nodule formation. This research presents the co-polymer DEGDMA/nOM as ideal
substrate to investigate the influence of stiffness on VIC differentiation
without the confounding effects of changing material surface chemistry. (c) 2016
Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 51-61, 2017.
PMID- 27513613
TI - NHC-Stabilized Silicon-Carbon Mixed Cumulene.
AB - The NHC-stabilized silicon-carbon mixed cumulene
(Me3Si)2C?Si(IPr)?Si(IPr)?C(SiMe3)2 (3, IPr = 1,3-diisopropyl-4,5-dimethyl
imidazol-2-ylidene) has been prepared by reaction of Ar(SiMe3)NK with the NHC
stabilized silene (Me3Si)2C?Si(SiMe3)Cl(IPr) (2) in toluene at low temperature
via the elimination of trimethylsilyl and chloride groups from 2. X-ray crystal
analysis of 3 indicated the formal C?Si?Si?C cumulene skeleton with the short Si
Si double bond distance of 2.1896(10) A. DFT calculations disclosed its
zwitterionic character. Reaction of 3 with diphenylacetylene resulted in the
formation of a silatriafulvene with an exocyclic NHC-stabilized silene moiety.
PMID- 27513614
TI - Real-world efficacy and safety of daclatasvir and asunaprevir therapy for
hepatitis C virus-infected cirrhosis patients.
AB - BACKGROUND AND AIMS: Daclatasvir and asunaprevir combination therapy has shown a
high virological response for chronic genotype 1 hepatitis C virus (HCV) infected
patients. However, the real-world efficacy and safety of the therapy for patients
with cirrhosis are unknown. METHODS: A total of 252 patients with genotype 1 HCV
infection (158 with chronic hepatitis and 94 with compensated liver cirrhosis)
were treated with 24 weeks of daclatasvir and asunaprevir combination therapy.
Plasma concentrations of daclatasvir and asunaprevir at day 5 of treatment, end
of-treatment response, sustained virological response (SVR), and the frequencies
of adverse events were analyzed. RESULT: Plasma asunaprevir concentration was
significantly higher, and daclatasvir concentration tended to be higher, in
cirrhosis patients compared with chronic hepatitis patients. End-of-treatment
response was achieved in 95.6% and 94.7% of chronic hepatitis and cirrhosis
patients, respectively, and SVR was achieved in 94.3% and 92.6%. Although pre
treatment NS5A drug resistant-associated variants were detected, a high SVR rate
was achieved when the population frequency of the variant was low. The
frequencies of treatment-related adverse events in cirrhosis patients were
similar to those in chronic hepatitis patients. Treatment discontinuation due to
adverse events occurred in three and two patients in chronic hepatitis and
cirrhosis groups, respectively; however, four out of five patients with treatment
discontinuation nonetheless achieved SVR. CONCLUSION: Patients with compensated
liver cirrhosis have similar virological response and tolerance for daclatasvir
plus asunaprevir therapy to patients with chronic hepatitis. This combination
therapy might offer a safe and effective treatment for chronic HCV infected
patients with compensated cirrhosis.
PMID- 27513615
TI - Direct Observation of Aggregation-Induced Backbone Conformational Changes in Tau
Peptides.
AB - In tau proteins, the hexapeptides in the R2 and R3 repeats are known to initiate
tau fibril formation, which causes a class of neurodegenerative diseases called
the taupathies. We show that in R3, in addition to the presence of the
hexapeptides, the correct turn conformation upstream to it is also essential for
producing prion-like fibrils that are capable of propagation. A time-dependent
NMR aggregation assay of a slow fibril forming R3-S316P peptide revealed a trans
to cis equilibrium shift in the peptide-bond conformation preceding P316 during
the growth phase of the aggregation process. S316 was identified as the key
residue in the turn that confers templating capacity on R3 fibrils to accelerate
the aggregation of the R3-S316P peptide. These results on the specific
interactions and conformational changes responsible for tau aggregation could
prove useful for developing an efficient therapeutic intervention in Alzheimer's
disease.
PMID- 27513619
TI - Immunotherapy to Treat Cancer.
AB - This issue of Clinical Pharmacology & Therapeutics focuses on immunotherapy as an
approach to treat cancer by generating or augmenting an immune response against
it. The enthusiasm for immunotherapy has waxed and waned over the past century.
Enthusiasm for immunotherapy has risen over the past decade due, in part, to data
showing that cancer immunotherapy consistently improves overall survival in
select patients with advanced-stage cancer. Antitumor immunotherapy has broad
potential and could be used to treat many different types of advanced-stage
cancer due to the durable and robust response that it elicits across a diverse
spectrum of cancers. This issue covers various aspects of relevant therapeutic
topics ranging from discovery of chimeric antigen receptor (CAR) T cells,
development of novel immunotherapies using novel pharmacokinetic/dynamic modeling
tools, to the utilization of immune checkpoint therapy. Regarding utilization,
this issue addresses biomarker selection strategies for personalized treatment of
non-small cell lung cancer (NSCLC) with immune checkpoint therapy and also the
management of the unique immune response adverse events (irAEs).
PMID- 27513622
TI - Theoretical and Experimental Insight on Ag2CrO4 Microcrystals: Synthesis,
Characterization, and Photoluminescence Properties.
AB - Ag2CrO4 microcrystals were synthesized by means of the coprecipitation method
without the use of a surfactant under three different conditions. On the basis of
the theoretical and experimental results, we describe the relationship among the
structural order/disorder effects, morphology, and photoluminescence of the
Ag2CrO4 microcrystals. The experimental results were correlated with the
theoretical findings for a deeper understanding of the relationship between the
electronic structure, morphology, and photoluminescence properties. First
principles computational studies were used to calculate the geometries of bulk
Ag2CrO4 and its low-index (001), (011), (110), (010), (111), and (100) facets
based on a slab model. A good agreement between the experimental and the
theoretical morphologies was found by varying the ratio of the superficial energy
values.
PMID- 27513623
TI - Sampling Enhancement and Free Energy Prediction by the Flying Gaussian Method.
AB - We present a novel sampling enhancement and free energy prediction technique
based on parallel simulation of the studied system with a shared bias potential.
This history-independent bias potential is defined using selected degrees of
freedom (collective variables). Each parallel walker of the system bears a single
Gaussian shaped bias potential centered in current values of collective
variables. Sampling enhancement is achieved by concentration of multiple walkers
in certain free energy minimum. The method was successfully demonstrated on
selected molecular systems, and presumed advantages over methods based on a
history-dependent bias potential are discussed.
PMID- 27513624
TI - Electrolyzed Saline Irrigation for Elimination of Bacterial Colonization in the
Empyema Space.
AB - BACKGROUND: The empyema space is refractory to elimination of bacterial
colonization. Electrolyzed saline (ES) was used as intra-pleural irrigation for
rapid disinfection of the empyema space. PATIENTS AND METHODS: Twenty consecutive
patients with para-pneumonic empyema were reviewed in this study from 2007 to
2015. The empyema space was irrigated by miniaturized thoracoscopic surgery (mini
VATS), and the efficacy and safety of the use of ES were evaluated. RESULTS:
Sixteen patients were male and four were female, with a mean age of 66.5 +/- 9.5
y (27-90 y). Bacterial cultures of the purulent effusions from all 20 patients
had positive results. Seventeen patients subsequently underwent continuous
catheter irrigation and drainage. No patient had chest pain during ES irrigation.
Fever duration after mini VATS was 2.8 +/- 1.8 d (0-5 d). Catheter indwelling
time was 10.3 +/- 7.2 d (3-33 d). Inflammatory markers significantly improved (p
< 0.05) within a week after mini VATS. Eighteen patients achieved pleural
disinfection, and two patients had residual pathogens, one of whom later died of
lung abscess. Space closure was successful in 14 patients. No patient underwent
subsequent open drainage. Nineteen (95%) patients were discharged from the
hospital. This treatment was successful in 18 (90%) patients, and one (5.6%)
patient experienced recurrence. CONCLUSIONS: The ES irrigation facilitates the
rapid disinfection and closure of the empyema space.
PMID- 27513625
TI - Errata: Vol. 65, No. 28.
AB - In the MMWR report, "Projected Zika Virus Importation and Subsequent Ongoing
Transmission after Travel to the 2016 Olympic and Paralympic Games - Country
Specific Assessment, July 2016," an error occurred throughout in reporting the
number of countries participating in the 2016 Olympic and Paralympic Games
without evidence of past Zika transmission: 18 countries (not 19 as stated) met
this criterion. Thus, the fourth sentence of the fourth paragraph should have
read, "For 14 of these countries, estimated aviation travel from Rio de Janeiro
in August 2016 compared with total aviation travel from all countries with local
Zika virus transmission in 2015 was 0.01%-3.04% (Table 2)." In addition, in Table
2, Angola should not have been listed, and the title should have read,
"Participating countries currently not reporting Zika outbreaks (n = 18) that met
risk criteria for Zika virus importation and subsequent ongoing transmission
attributed to travel to the Olympic and Paralympic Games, ranked by aviation
travel volume* from Rio de Janeiro, Brazil - August 2016."
PMID- 27513627
TI - Psychometric equivalence of electronic and telephone completion of the ICIQ
modules.
AB - AIMS: To assess the equivalence of touch-screen (hand-held iPad) and telephone
completion of patient-completed International Consultation on Incontinence
Questionnaire (ICIQ) modules by comparison with corresponding data collected
using conventional paper-and-pencil methods. METHODS: Men and women, attending
urology outpatients complaining of LUTS, were randomised to one of three groups
which determined the order in which they completed three administrations of the
same questionnaire: paper, iPad and telephone. Four ICIQ questionnaires were
evaluated: ICIQ-MLUTS, ICIQ-LUTSqol, ICIQ-OABqol and ICIQ-UI SF. RESULTS: From
August 2012 to October 2014 a total of 448 out of 491 (91%) recruits completed
the first two administrations and were included in the analysis. Three hundred
forty-eight out of 491 (71%) completed the phone administration. The intra-class
correlation coefficient (ICC) and Kappa statistic were calculated where
appropriate between completed pairs of administrations. Mean ICC correlations
were high (>0.8) between paper and iPad administrations. Paired paper and phone
administrations were less well correlated, although still high (mean ICC>0.75).
This may be partly due to the practical limitation that the phone interview was
completed up to a week later than the initial two administrations. There was no
evidence that potential moderator effects (gender, age and experience with
computers or touch screen devices) significantly affected overall reliability of
scores between administrations. CONCLUSIONS: We can recommend the interchangeable
use of ICIQ electronic or paper based questionnaires in a clinical or research
setting. Self-report is preferable to telephone delivery where possible.
Neurourol. Urodynam. 9999:XX-XX, 2016. (c) 2016 Wiley Periodicals, Inc.
PMID- 27513630
TI - Exogenous hydrogen sulfide exerts proliferation, anti-apoptosis, migration
effects and accelerates cell cycle progression in multiple myeloma cells via
activating the Akt pathway.
AB - Hydrogen sulfide (H2S), regarded as the third gaseous transmitter, mediates and
induces various biological effects. The present study investigated the effects of
H2S on multiple myeloma cell progression via amplifying the activation of Akt
pathway in multiple myeloma cells. The level of H2S produced in multiple myeloma
(MM) patients and healthy subjects was measured using enzyme-linked immunosorbent
assay (ELISA). MM cells were treated with 500 umol/l NaHS (a donor of H2S) for 24
h. The expression levels of phosphorylated-Akt (p-Akt), Bcl-2 and caspase-3 were
measured by western blot assay. Cell viability was detected by Cell Counting Kit
8 (CCK-8). The cell cycle was analyzed by flow cytometry. Our results show that
the concentration of H2S was higher in MM patients and that it increased in
parallel with disease progression. Treating MM cells with 500 umol/l NaHS for 24
h markedly increased the expression level of Bcl-2 and the activation of p-Akt,
however, the expression level of caspase-3 was decreased, cell viability was
increased, and cell cycle progression was accelerated in MM cells. NaHS also
induced migration in MM cells in transwell migration assay. Furthermore, co
treatment of MM cells with 500 umol/l NaHS and 50 umol/l LY294002 for 24 h
significantly overset these effects. In conclusion, our findings demonstrate that
the Akt pathway contributes to NaHS-induced cell proliferation, migration and
acceleration of cell cycle progression in MM cells.
PMID- 27513629
TI - Long-Term Training with a Brain-Machine Interface-Based Gait Protocol Induces
Partial Neurological Recovery in Paraplegic Patients.
AB - Brain-machine interfaces (BMIs) provide a new assistive strategy aimed at
restoring mobility in severely paralyzed patients. Yet, no study in animals or in
human subjects has indicated that long-term BMI training could induce any type of
clinical recovery. Eight chronic (3-13 years) spinal cord injury (SCI)
paraplegics were subjected to long-term training (12 months) with a multi-stage
BMI-based gait neurorehabilitation paradigm aimed at restoring locomotion. This
paradigm combined intense immersive virtual reality training, enriched visual
tactile feedback, and walking with two EEG-controlled robotic actuators,
including a custom-designed lower limb exoskeleton capable of delivering tactile
feedback to subjects. Following 12 months of training with this paradigm, all
eight patients experienced neurological improvements in somatic sensation (pain
localization, fine/crude touch, and proprioceptive sensing) in multiple
dermatomes. Patients also regained voluntary motor control in key muscles below
the SCI level, as measured by EMGs, resulting in marked improvement in their
walking index. As a result, 50% of these patients were upgraded to an incomplete
paraplegia classification. Neurological recovery was paralleled by the
reemergence of lower limb motor imagery at cortical level. We hypothesize that
this unprecedented neurological recovery results from both cortical and spinal
cord plasticity triggered by long-term BMI usage.
PMID- 27513631
TI - The influence of early depressive symptoms, social support and decreasing self
efficacy on depression 6 months post-stroke.
AB - BACKGROUND: Post-stroke depression (PSD) is the most frequent mental disorder
after stroke, affecting about 30% of stroke survivors. Despite extensive
research, little is known about the influence of general self-efficacy (GSE) on
PSD. We investigated the effect of GSE on depression six months post-stroke while
controlling for established risk factors. METHODS: Eighty-eight patients from two
rehabilitation centers with first-ever ischemic stroke were assessed around 8
weeks and 6 months after stroke. Baseline assessment included demographic
variables, GSE scale, physical disability (Barthel-Index), stroke severity
(modified NIH Scale), pre-stroke mental illness, cognitive status (Mini-Mental
State-Test), social support (F-SozU Questionnaire) and depressiveness (Geriatric
Depression Scale, GDS). Follow-up assessment included DSM-IV depression, GDS and
GSE. The influence of each risk factor on PSD was analyzed by binary hierarchical
regression. RESULTS: Baseline depressiveness (OR=1.41, p<.01) and social support
(OR=.95, p=.03) predicted PSD. Decreasing GSE was associated with high baseline
GSE (r=.51, p<.01) and influenced later PSD (OR=1.39, p<.01). LIMITATIONS:
Patients' range of impairment may have been limited as sufficient speech
comprehension and capacity for interview participation were required. Causal
relationship between decreasing GSE and increasing GDS cannot be assumed based on
correlations. DISCUSSION: Decreasing GSE was linked to PSD, especially in
patients with high baseline GSE. This effect may be due to dissatisfaction with
recovery following high expectations. Early depressive symptoms and low social
support predicted PSD. Early screening for depressive symptoms and focusing on
self-efficacy might help to prevent later depression.
PMID- 27513632
TI - miR-221 targets HMGA2 to inhibit bleomycin-induced pulmonary fibrosis by
regulating TGF-beta1/Smad3-induced EMT.
AB - MicroRNA (miR)-221 plays an essential role in the epithelial-mesenchymal
transition (EMT). High mobility group AT-hook 2 (HMGA2), is a key regulator of
EMT. However, the role of miR-221 in pulmonary fibrosis, and the association
between miR-221 and HMGA2 remain largely unknown. For this purpose, we examined
the expression of miR-221 and HMGA2 in human idiopathic pulmonary fibrosis (IPF)
tissues and pulmonary cells, namely the adenocarcinoma A549 and human bronchial
epithelium (HBE) cell lines, and found that the expression of miR-221 was
inhibited in both tissues and cells whereas high mRNA and protein expression of
HMGA2 was observed. Additionally, transforming growth factor-beta1 (TGF-beta1)
induced the EMT, characterized by the upregulated expression of the mesenchymal
markers, namely N-cadherin, vimentin, alpha-smooth muscle actin, collagen I and
collagen III, and the downregulated expression of the epithelial marker E
cadherin in A549 and HBE cells. We then performed transfection with miR-221
mimics, and found that the expression of phosphorylated-Smad3 in miR-221
overexpressing cells was significantly downregulated, compared with that in the
TGF-beta1-treated cells without transfection. Furthermore, the overexpression of
miR-221 decreased the expression of HMGA2, suppressed the EMT, and inhibited the
proliferation of A549 and HBE cells. HMGA2 was directly targeted by miR-221 which
was confirmed by the dual-luciferase reporter gene assay. Finally, a mouse model
of bleomycin (BLM)-induced pulmonary fibrosis was used to confirm the effect of
miR-221 on EMT. Hematoxylin and eosin staining showed that BLM induced thicker
alveolar walls and more collagen deposition, whereas miR-221 treatment reduced
lung fibrosis and the tissues exhibited thinner alveolar walls and normal lung
alveoli. Furthermore, the EMT process was suppressed following miR-221 injection.
Taken together, these findings sugest that miR-221 targets HMGA2 to inhibit BLM
induced pulmonary fibrosis through the TGF-beta1/Smad3 signaling pathway.
PMID- 27513633
TI - Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of
Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.
AB - OBJECTIVES: Electrical neuromodulation by spinal cord stimulation (SCS) is a well
established method for treatment of neuropathic pain. However, the mechanism
behind the pain relieving effect in patients remains largely unknown. In this
study, we target the human cerebrospinal fluid (CSF) proteome, a little
investigated aspect of SCS mechanism of action. METHODS: Two different proteomic
mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive
neuropathic pain patients. Each patient acted as his or her own control and
protein content was compared when the stimulator was turned off for 48 hours, and
after the stimulator had been used as normal for three weeks. RESULTS: Eighty-six
proteins were statistically significantly altered in the CSF of neuropathic pain
patients using SCS, when comparing the stimulator off condition to the stimulator
on condition. The top 12 of the altered proteins are involved in neuroprotection
(clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4
protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1,
apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein),
nociceptive signaling (neurosecretory protein VGF), and immune regulation
(dickkopf-related protein 3). CONCLUSION: Previously unknown effects of SCS on
levels of proteins involved in neuroprotection, nociceptive signaling, immune
regulation, and synaptic plasticity are demonstrated. These findings, in the CSF
of neuropathic pain patients, expand the picture of SCS effects on the
neurochemical environment of the human spinal cord. An improved understanding of
SCS mechanism may lead to new tracks of investigation and improved treatment
strategies for neuropathic pain.
PMID- 27513635
TI - Occurrence and Potential Biological Effects of Amphetamine on Stream Communities.
AB - The presence of pharmaceuticals, including illicit drugs in aquatic systems, is a
topic of environmental significance because of their global occurrence and
potential effects on aquatic ecosystems and human health, but few studies have
examined the ecological effects of illicit drugs. We conducted a survey of
several drug residues, including the potentially illicit drug amphetamine, at 6
stream sites along an urban to rural gradient in Baltimore, Maryland, U.S.A. We
detected numerous drugs, including amphetamine (3 to 630 ng L(-1)), in all stream
sites. We examined the fate and ecological effects of amphetamine on biofilm,
seston, and aquatic insect communities in artificial streams exposed to an
environmentally relevant concentration (1 MUg L(-1)) of amphetamine. The
amphetamine parent compound decreased in the artificial streams from less than 1
MUg L(-1) on day 1 to 0.11 MUg L(-1) on day 22. In artificial streams treated
with amphetamine, there was up to 45% lower biofilm chlorophyll a per ash-free
dry mass, 85% lower biofilm gross primary production, 24% greater seston ash-free
dry mass, and 30% lower seston community respiration compared to control streams.
Exposing streams to amphetamine also changed the composition of bacterial and
diatom communities in biofilms at day 21 and increased cumulative dipteran
emergence by 65% and 89% during the first and third weeks of the experiment,
respectively. This study demonstrates that amphetamine and other biologically
active drugs are present in urban streams and have the potential to affect both
structure and function of stream communities.
PMID- 27513636
TI - Affective Pictures and the Open Library of Affective Foods (OLAF): Tools to
Investigate Emotions toward Food in Adults.
AB - Recently, several sets of standardized food pictures have been created, supplying
both food images and their subjective evaluations. However, to date only the OLAF
(Open Library of Affective Foods), a set of food images and ratings we developed
in adolescents, has the specific purpose of studying emotions toward food.
Moreover, some researchers have argued that food evaluations are not valid across
individuals and groups, unless feelings toward food cues are compared with
feelings toward intense experiences unrelated to food, that serve as benchmarks.
Therefore the OLAF presented here, comprising a set of original food images and a
group of standardized highly emotional pictures, is intended to provide valid
between-group judgments in adults. Emotional images (erotica, mutilations, and
neutrals from the International Affective Picture System/IAPS) additionally
ensure that the affective ratings are consistent with emotion research. The OLAF
depicts high-calorie sweet and savory foods and low-calorie fruits and
vegetables, portraying foods within natural scenes matching the IAPS features. An
adult sample evaluated both food and affective pictures in terms of pleasure,
arousal, dominance, and food craving, following standardized affective rating
procedures. The affective ratings for the emotional pictures corroborated
previous findings, thus confirming the reliability of evaluations for the food
images. Among the OLAF images, high-calorie sweet and savory foods elicited the
greatest pleasure, although they elicited, as expected, less arousal than
erotica. The observed patterns were consistent with research on emotions and
confirmed the reliability of OLAF evaluations. The OLAF and affective pictures
constitute a sound methodology to investigate emotions toward food within a wider
motivational framework. The OLAF is freely accessible at digibug.ugr.es.
PMID- 27513637
TI - Metabolic Network for the Biosynthesis of Intra- and Extracellular alpha-Glucans
Required for Virulence of Mycobacterium tuberculosis.
AB - Mycobacterium tuberculosis synthesizes intra- and extracellular alpha-glucans
that were believed to originate from separate pathways. The extracellular glucose
polymer is the main constituent of the mycobacterial capsule that is thought to
be involved in immune evasion and virulence. However, the role of the alpha
glucan capsule in pathogenesis has remained enigmatic due to an incomplete
understanding of alpha-glucan biosynthetic pathways preventing the generation of
capsule-deficient mutants. Three separate and potentially redundant pathways had
been implicated in alpha-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the
Rv3032 and the TreS-Pep2-GlgE pathways. We now show that alpha-glucan in
mycobacteria is exclusively assembled intracellularly utilizing the building
block alpha-maltose-1-phosphate as the substrate for the maltosyltransferase
GlgE, with subsequent branching of the polymer by the branching enzyme GlgB. Some
alpha-glucan is exported to form the alpha-glucan capsule. There is an unexpected
convergence of the TreS-Pep2 and GlgC-GlgA pathways that both generate alpha
maltose-1-phosphate. While the TreS-Pep2 route from trehalose was already known,
we have now established that GlgA forms this phosphosugar from ADP-glucose and
glucose 1-phosphate 1000-fold more efficiently than its hitherto described
glycogen synthase activity. The two routes are connected by the common precursor
ADP-glucose, allowing compensatory flux from one route to the other. Having
elucidated this unexpected configuration of the metabolic pathways underlying
alpha-glucan biosynthesis in mycobacteria, an M. tuberculosis double mutant
devoid of alpha-glucan could be constructed, showing a direct link between the
GlgE pathway, alpha-glucan biosynthesis and virulence in a mouse infection model.
PMID- 27513638
TI - Prevalent Accumulation of Non-Optimal Codons through Somatic Mutations in Human
Cancers.
AB - Cancer is characterized by uncontrolled cell growth, and the cause of different
cancers is generally attributed to checkpoint dysregulation of cell proliferation
and apoptosis. Recent studies have shown that non-optimal codons were
preferentially adopted by genes to generate cell cycle-dependent oscillations in
protein levels. This raises the intriguing question of how dynamic changes of
codon usage modulate the cancer genome to cope with a non-controlled
proliferative cell cycle. In this study, we comprehensively analyzed the somatic
mutations of codons in human cancers, and found that non-optimal codons tended to
be accumulated through both synonymous and non-synonymous mutations compared with
other types of genomic substitution. We further demonstrated that non-optimal
codons were prevalently accumulated across different types of cancers, amino
acids, and chromosomes, and genes with accumulation of non-optimal codons tended
to be involved in protein interaction/signaling networks and encoded important
enzymes in metabolic networks that played roles in cancer-related pathways. This
study provides insights into the dynamics of codons in the cancer genome and
demonstrates that accumulation of non-optimal codons may be an adaptive strategy
for cancerous cells to win the competition with normal cells. This deeper
interpretation of the patterns and the functional characterization of somatic
mutations of codons will help to broaden the current understanding of the
molecular basis of cancers.
PMID- 27513639
TI - Effectiveness of Periosteal Stimulation Therapy and Home Exercise Program in the
Rehabilitation of Patients With Advanced Knee Osteoarthritis.
AB - BACKGROUND: Osteoarthritis (OA) of the knee is the most common form of joint
disease. It is one of the major causes of impaired function that reduces quality
of life in older people worldwide. Periosteal Stimulation Therapy (PST) with
boosters in combination with home exercises may be a suitable treatment option
for such patients. OBJECTIVES: To examine the effectiveness of PST with boosters
in addition to a home-based exercise program as compared with Transcutaneous
Electrical Nerve Stimulation (TENS) combined with the same home-based exercise
program in the management of chronic pain and functional impairments associated
with advanced knee OA. DESIGN: The study was a randomized controlled trial.
MATERIALS AND METHODS: Sixty patients with Kellgren-Lawrence grade 3 or 4 knee OA
were randomized to receive PST or TENS once a week for 10 weeks, followed by
boosters for 6 months in addition to a home exercise program. Visual Analogue
Scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales
were assessed at baseline, after the last PST session, and 6 months later.
RESULTS: Pain VAS and KOOS subscales were improved in both PST and TENS groups at
10 weeks and 6 months after intervention, with a statistically significant
difference between the groups at both follow-up periods. Reduced pain VAS and
increased KOOS subscales in the PST group were statistically significantly
different from the TENS group during both follow-up periods. CONCLUSION: PST with
boosters combined with a home exercise program was shown to be beneficial for
improving subjective knee pain and functional performance of older patients with
advanced knee OA.
PMID- 27513640
TI - Effect of Epidural Dexmedetomidine Combined With Ropivacaine in Labor Analgesia:
A Randomized Double-Blinded Controlled Study.
AB - BACKGROUND: The purpose of our study is to evaluate the effect of adding
dexmedetomidine to epidural ropivacaine in patients undergoing labor epidural
analgesia. METHODS: Eighty healthy women were randomly assigned to 2 groups:
control group (R; n=40) received epidural 0.125% ropivacaine for labor analgesia,
whereas the study group (D; n=40) received epidural 0.125% ropivacaine with
dexmedetomidine in addition. The blood pressure, heart rate, and the severity of
pain of the parturient was assessed, the duration of the first stage and the
second stage of labor time, the rate of instrumental delivery and the rate of
cesarean section were recorded. The side effects (nausea and vomiting), intensity
of maternal sedation, and neonatal Apgar scores were also recorded. RESULTS: The
visual analog scales, systolic blood pressure, diastolic blood pressure, and
heart rates of D group were significant lower than that of R group at most time
intervals after epidural analgesia. The duration of the first and second stage of
labor, the rate of instrumental delivery and cesarean section, neonatal 1- and 5
minute Apgar scores, umbilical artery pH, maternal motor blockade scores,
intensity of maternal sedation, and the incidence of maternal complications did
not show significant difference between 2 groups. CONCLUSIONS: Low concentration
of epidural ropivacaine (0.125%) combined with dexmedetomidine (0.5 MUg/kg)
reduces the feeling of pain, and does not show the problems of motor blockage,
hemodynamic instability, extension of production process, and complications such
as nausea and vomiting. Our study was registered with Chinese Clinical Trial
Registry (ChiCTR-IOR-15007263).
PMID- 27513641
TI - Trends in the Nonmedical Use of OxyContin, United States, 2006 to 2013.
AB - OBJECTIVES: The role of the opioid OxyContin in the opioid abuse epidemic has
been well documented. In 2010, OxyContin was reformulated to make it more
difficult to abuse. We assessed past-year OxyContin nonmedical use among a
nationally representative population and among nonmedical users of opioid pain
relievers in the United States between 2006 and 2013. MATERIALS AND METHODS: Data
are from the National Survey on Drug Use and Health. Prevalence estimates of past
year OxyContin nonmedical use overall and by sociodemographic, geographic, and
substance use characteristics were calculated for each year, 2006 through 2013.
Multivariable logistic regression was used to identify individual characteristics
associated with past-year OxyContin nonmedical use before and after
reformulation. RESULTS: In 2013, the of past-year nonmedical use of OxyContin
among people 12 years and older in the United States was 0.5%. This was
significantly lower than the prevalence in 2010 (0.7%; P<0.05), but was similar
to that in 2006 to 2009 and 2011 to 2012. Among past-year nonmedical users of
pain relievers in 2013, the prevalence of OxyContin nonmedical use was 13.0%.
This was significantly higher than the prevalence in 2006 (10.5%; P<0.05), and
was similar to that in 2007 through 2012. Groups with increased odds of using
OxyContin nonmedically in the past-year were similar before and after
reformulation (2009-2010 and 2012-2013, respectively). For 2012-2013, odds for
past-year OxyContin nonmedical use after reformulation were greatest for: people
reporting >=200 days of pain reliever nonmedical use, adjusted odds ratio
(aOR)=3.61 (95% confidence interval [CI], 2.47-5.28); past-year heroin users,
aOR=3.45 (95% CI, 2.22-5.37); and people with past-year pain reliever abuse or
dependence, aOR=2.57 (95% CI, 1.88-3.51). DISCUSSION: The prevalence of past-year
OxyContin nonmedical use in 2013, 3 years after reformulation, was significantly
lower than the prevalence in the reformulation year, but similar to other years
before and after reformulation. The prevalence of OxyContin nonmedical use among
nonmedical users of pain relievers was higher than or similar to historical
prevalence rates before reformulation. Groups with increased odds of OxyContin
nonmedical use were similar before and after reformulation.
PMID- 27513642
TI - The Influence of Seasonality and Community-Based Health Worker Provided
Counselling on Exclusive Breastfeeding - Findings from a Cross-Sectional Survey
in India.
AB - BACKGROUND: Exclusive breastfeeding (EBF) during the first six months of life is
considered a high impact but low-cost measure for reducing the morbidity and
mortality among children. The current study investigated the association of
seasonality and frontline worker(FLW) provided counselling with practice of EBF
in Bihar, India. METHODS: We used the 'Lot Quality Assurance Sampling' technique
to conduct a multi-stage sampling survey in 8 districts of Bihar. Regarding EBF,
mothers of 0-5 (completed) months old children were asked if they had given only
breastmilk to their children during the previous day, while mothers of 6-8
(completed) months old children were inquired about the total duration of EBF. We
tested for association between EBF during the previous day with season of
interview and EBF for full 6 months with nursing season. We also assessed if
receiving counselling on EBF and complementary feeding had any association with
relevant EBF indicators. RESULTS: Among the under-6 month old children, 76%
received EBF during the previous day, whereas 92% of 6-8 (completed) months old
children reportedly received EBF for the recommended duration. Proportion of 0-5
(completed) month old children receiving only breastmilk (during last 24 hours)
decreased significantly with increasing age and with change of season from colder
to warmer months. Odds of receiving only breastmilk during the previous day was
significantly higher during the winter months (Adjusted odds ratio(AOR) = 1.50;
95% CI = 1.37, 1.63) compared to summer. Also, the children nursed primarily
during the winter season had higher odds of receiving EBF for 6 months (AOR =
1.90, 95% CI = 1.43, 2.52) than those with non-winter nursing. Receiving FLW
counselling was positively associated with breastfeeding exclusively, even after
adjusting for seasonality and other covariates (AOR = 1.82; 95% CI = 1.67, 1.98).
CONCLUSIONS: Seasonality is a significant but non-modifiable risk factor for EBF.
However, FLW-counselling was found to increase practice of EBF irrespective of
season. Scale-up of FLW-counselling services, with emphasis on summer months and
mothers of older infants, can potentially reduce the impact of seasonality on
EBF.
PMID- 27513643
TI - Posterior Decompression and Fusion: Whole-Spine Functional and Clinical Outcomes.
AB - The mobility of the spine and the change in the angle of the curvatures are
directly related to spinal pain and spinal stenosis. The aim of the study was the
evaluation of morphology and mobility of the spine in patients who were subjected
to decompression and posterior fusion with pedicle screws. The treatment group
consisted of 20 patients who underwent posterior fixation of lumbar spine (one
and two level fusion). The control group consisted of 39 healthy subjects.
Mobility and curvatures of the spine were measured with a non-invasive device,
the Spinal Mouse. Pain was evaluated with the Visual Analogue Scale (VAS). The
Oswestry Disability Index (ODI) and the SF-36 were used to evaluate the degree of
the functional disability and the quality of life, respectively. The measurements
were recorded preoperatively and at 3, 6 and 12 months postoperatively. The
mobility of the lumbar spine in the sagittal plane increased (p = 0.009) at 12
months compared to the measurements at 3 months. The mobility of the thoracic
spine in the frontal plane increased (p = 0.009) at 12 months compared to the
preoperative evaluation. The results of VAS, ODI and SF-36 PCS improved
significantly (p<0.001). The levels of fusion exhibited a strong linear
correlation (r = 0.651, p = 0.002) with the total trunk inclination in the
upright position. Although pain, quality of life and spinal mobility in the
sagittal and frontal planes significantly improved in the treatment group, these
patients still had limited mobility and decreased curves/angles values compared
to control group.
PMID- 27513644
TI - Combating the Sigatoka Disease Complex on Banana.
PMID- 27513645
TI - Combustion reaction kinetics of guarana seed residue applying isoconversional
methods and consecutive reaction scheme.
AB - This work aims the study of decomposition kinetics of guarana seed residue using
thermogravimetric analyzer under synthetic air atmosphere applying heating rates
of 5, 10, and 15 degrees C/min, from room temperature to 900 degrees C. Three
thermal decomposition stages were identified: dehydration (25.1-160 degrees C),
oxidative pyrolysis (240-370 degrees C), and combustion (350-650 degrees C). The
activation energies, reaction model, and pre-exponential factor were determined
through four isoconversional methods, master plots, and linearization of the
conversion rate equation, respectively. A scheme of two-consecutive reactions was
applied validating the kinetic parameters of first-order reaction and two
dimensional diffusion models for the oxidative pyrolysis stage (149.57kJ/mol,
6.97*10(10)1/s) and for combustion stage (77.98kJ/mol, 98.611/s), respectively.
The comparison between theoretical and experimental conversion and conversion
rate showed good agreement with average deviation lower than 2%, indicating that
these results could be used for modeling of guarana seed residue.
PMID- 27513646
TI - In situ activity recovery of aging biofilm in biological aerated filter:
Surfactants treatment and mechanisms study.
AB - In situ activity recovery of aging biofilm in the biological aerated filter (BAF)
is an important but underappreciated problem. Lab-scaled BAFs were established in
this study and three kinds of surfactants containing sodium dodecyl sulfate
(SDS), sodium dodecyl benzene sulfonate (SDBS) and rhamnolipid were employed.
Multiple indicators including effluent qualities, dissolved organic matters,
biofilm physiology and morphology characteristics were investigated to explore
the mechanisms. Results showed that removal rates of effluent COD in test groups
significantly recovered to the level before aging. Compared with the control,
effluent in SDBS and rhamnolipid-treated groups obtained more protein-like and
humic-like substances, respectively. Furthermore, great live cell ratio, smooth
surface and low adhesion force of biofilm were observed after rhamnolipid
treatment, which was in consistent with good effluent qualities in the same
group. This is the first report of applying rhamnolipid for in situ activity
recovery of aging biofilm in bioreactors.
PMID- 27513647
TI - Impact of partial nitritation degree and C/N ratio on simultaneous Sludge
Fermentation, Denitrification and Anammox process.
AB - This study presents a novel process (i.e. PN/SFDA) to remove nitrogen from low
C/N domestic wastewater. The process mainly involves two reactors, a pre
Sequencing Batch Reactor for partial nitritation (termed as PN-SBR) and an anoxic
reactor for integrated Denitrification and Anammox with carbon sources produced
from Sludge Fermentation (termed as SFDA). During long-term Runs, NO2(-)/NH4(+)
ratio (i.e. NO2(-)-N/NH4(+)-N calculated by mole) in the PN-SBR effluent was
gradually increased from 0.2 to 37 by extending aerobic duration, meaning that
partial nitritation turning to full nitritation could be achieved. Impact of
partial nitritation degree on SFDA process was investigated and the result showed
that, NO2(-)/NH4(+) ratios between 2 and 10 were appropriate for the co-existence
of denitrification and anammox together in the SFDA reactor, and denitrification
instead of anammox contributed greater for nitrogen removal. Further batch tests
indicated that anammox collaborated well with denitrification at low C/N (1.0 in
this study).
PMID- 27513648
TI - Simultaneous saccharification and fermentation of hemicellulose to butanol by a
non-sporulating Clostridium species.
AB - Production of lignocellulosic butanol has drawn increasing attention. However,
currently few microorganisms can produce biofuels, particularly butanol, from
lignocellulosic biomass via simultaneous saccharification and fermentation. Here
we report discovery of a wild-type, mesophilic Clostridium sp. strain MF28 that
ferments xylan to produce butanol (up to 3.2g/L) without the addition of
saccharolytic enzymes and without any chemical pretreatments. Application of
selective pressure from 2-deoxy-d-glucose facilitated isolation of strain MF28,
which exhibits inactivation of genes (gid and ccp genes) responsible for carbon
catabolite repression, thus allowing strain MF28 to simultaneously ferment a
combination of glucose (30g/L), xylose (15g/L), and arabinose (15g/L) to produce
11.9g/L of butanol. Strain MF28 possesses several unique features: (i) non
sporulating, (ii) no acetone/ethanol, (iii) complete hemicellulose-binding
enzymatic domain, and (iv) absence of carbon catabolite repression. These unique
characteristics demonstrate the industrial potential of strain MF28 for cost
effective biofuel generation from lignocellulosic biomass.
PMID- 27513649
TI - Hidden Genetic Diversity in an Asexually Reproducing Lichen Forming Fungal Group.
AB - Asexual species with vegetative propagation of both symbiont partners (soredia)
in lichens may harbor lower species diversity because they may indeed represent
evolutionary dead ends or clones. In this study we aim to critically examine
species boundaries in the sorediate lichen forming fungi Parmotrema reticulatum
Parmotrema pseudoreticulatum complex applying coalescent-based approaches and
other recently developed DNA-based methods. To this end, we gathered 180 samples
from Africa, Asia, Australasia, Europe, North and South America and generated
sequences of internal transcribed spacer of nuclear ribosomal DNA (ITS) and DNA
replication licensing factor MCM7 (MCM7). The dataset was analysed using
different approaches such as traditional phylogeny-maximum likelihood and
Bayesian-genetic distances, automatic barcode gap discovery and coalescent-based
methods-PTP, GMYC, spedeSTEM and *Beast-in order to test congruence among
results. Additionally, the divergence times were also estimated to elucidate
diversification events. Delimitations inferred from the different analyses are
comparable with only minor differences, and following a conservative approach we
propose that the sampled specimens of the P. reticulatum-P. pseudoreticulatum
complex belong to at least eight distinct species-level lineages. Seven are
currently classified under P. reticulatum and one as P. pseudoreticulatum. In
this work we discuss one of only few examples of cryptic species that have so far
been found in sorediate reproducing lichen forming fungi. Additionally our
estimates suggest a recent origin of the species complex-during the Miocene.
Consequently, the wide distribution of several of the cryptic species has to be
explained by intercontinental long-distance dispersal events.
PMID- 27513650
TI - The effects of exercise modality on maximal and submaximal exercise parameters
obtained by graded maximal exercise testing.
AB - BACKGROUND: Cardiopulmonary exercise testing (CPET) has become part of screening
and evaluation in cardiology. The exercise modalities most often used in CPET are
the treadmill (TM) and upright bicycle (UB). Nowadays, also the supine bicycle
(SB) is becoming more often used, especially when combined with cardiac imaging.
OBJECTIVES: Our aim was to examine whether a maximal CPET on a SB leads to
similar results as TM and UB in terms of different CPET measures. Secondly, we
explored whether peak VO2 relates to the person's preference and experience with
the different exercise modalities. METHODS: Twelve healthy individuals (8 male;
mean age 21.6, range 21-24) participated in a randomized controlled cross-over
trial and performed 3 maximal CPETs on a TM, UB and SB. Repeated measures ANOVA
was performed to evaluate differences between tests. Further, Intraclass
correlation coefficients (ICC) and Bland-Altman plots were obtained. RESULTS: The
SB CPET resulted in lower peak VO2 (2806+/-652ml.min(-1) (SB) vs 3329+/
798ml.min(-1) (UB) and 3550+/-799ml.min(-1) (TM); p<0.001) and peak heart rate
(179+/-8 beats.min(-1) (SB) vs 192+/-7 beats.min(-1) (UB) and 193+/-11 beats.min(
1) (TM); p<0.001). VE/VCO2-slope did not differ between the 3 modalities.
Overall, ICC and Bland-Altman plots showed low agreement for SB measures. No
influence of preference and experience on peak VO2 could be found. CONCLUSION:
Upcoming maximal SB exercise tests, for evaluations in clinical settings, can't
be considered as an evaluation of the maximal exercise capacity when compared to
golden standard TM and UB.
PMID- 27513651
TI - Differing predictive relationships between baseline LDL-C, systolic blood
pressure, and cardiovascular outcomes.
AB - BACKGROUND: Traditional cardiovascular risk factors, such as hypertension and
dyslipidemia, predispose individuals to cardiovascular disease, particularly
patients with diabetes. We investigated the predictive value of baseline systolic
blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) on the risk
of vascular outcomes in a large population of patients at high risk of future
cardiovascular events. METHODS: Data were pooled from the TNT (Treating to New
Targets), CARDS (Collaborative Atorvastatin Diabetes Study), and IDEAL
(Incremental Decrease in End-Points Through Aggressive Lipid Lowering) trials and
included a total of 21,727 patients (TNT: 10,001; CARDS: 2838; IDEAL: 8888). The
effect of baseline SBP and LDL-C on cardiovascular events, coronary events, and
stroke was evaluated using a multivariate Cox proportional-hazards model.
RESULTS: Overall, risk of cardiovascular events was significantly higher for
patients with higher baseline SBP or LDL-C. Higher baseline SBP was significantly
predictive of stroke but not coronary events. Conversely, higher baseline LDL-C
was significantly predictive of coronary events but not stroke. Results from the
subgroup with diabetes (5408 patients; TNT: 1501; CARDS: 2838; IDEAL: 1069) were
broadly consistent with those of the total cohort: baseline SBP and LDL-C were
significantly predictive of cardiovascular events overall, with the association
to LDL-C predominantly related to an effect on coronary events. However, baseline
SBP was not predictive of either coronary or stroke events in the pooled diabetic
population. CONCLUSIONS: In this cohort of high-risk patients, baseline SBP and
LDL-C were significantly predictive of cardiovascular outcomes, but this effect
may differ between the cerebrovascular and coronary systems. TRIAL REGISTRATION
NUMBER: NCT00327691 (TNT); NCT00327418 (CARDS); NCT00159835 (IDEAL).
PMID- 27513652
TI - Outcome and incidence of appropriate implantable cardioverter-defibrillator
therapy in patients with cardiac amyloidosis.
AB - BACKGROUND: Cardiac amyloidosis (CA) is associated with a poor prognosis with the
proposed mechanism of sudden cardiac death in the majority of patients being
pulseless electrical activity. However, the incidence of ventricular arrhythmias
(VA) and implantable cardioverter-defibrillator (ICD) indications in CA patients
are unclear. We performed a detailed evaluation of our CA population undergoing
ICD implantation and assessed appropriate ICD therapy and survival predictors.
METHODS: We included consecutive patients from June 2008 to November 2014 in five
centers. ICDs were systematically interrogated and clinical data recorded during
follow-up. RESULTS: Forty-five patients (35 males, mean age 66+/-12years) with CA
who underwent ICD implantation (84.4% primary prevention) were included. CA types
were hereditary transthyretin in 27 patients (60%), light chain (AL) in 12 (27%)
and senile in 6 (13%). After a mean follow-up of 17+/-14months, 12 patients (27%)
had at least 1 appropriate ICD therapy occurring after 4.7+/-6.6months. Patients
with or without ICD therapy had no significant differences in baseline
characteristics, amyloidosis type, LVEF, and type of prevention although there
was a trend towards a better 2D global longitudinal strain in patients with ICD
therapy (P=0.08). Over the follow-up, 12 patients died (27%) and 6 underwent
cardiac transplantation (13%). From multivariate analysis a worse prognosis was
associated with higher NT-proBNP level (>6800pg/mL, HR=5.5[1.7-17.8]) and AL type
(HR=4.9[1.5-16.3]). CONCLUSIONS: Appropriate ICD therapies are common (27%) in CA
patients. No specific strong VA predictor could be identified. However, patients
with advanced heart disease, especially with AL-CA, display a poorer outcome.
PMID- 27513653
TI - Effects of early aldosterone antagonism on cardiac remodeling in rats with aortic
stenosis-induced pressure overload.
AB - Aldosterone plays a pivotal role in the pathophysiology of systolic heart
failure. However, whether early aldosterone antagonism improves cardiac
remodeling during persistent pressure overload is unsettled. We evaluated the
effects of aldosterone antagonist spironolactone on cardiac remodeling in rats
with ascending aortic stenosis (AS). METHODS: Three days after inducing AS,
weaning rats were randomized to receive spironolactone (AS-SPR, 20mg/kg/day) or
no drug (AS) for 18weeks, and compared with sham-operated rats. Myocardial
function was studied in isolated left ventricular (LV) papillary muscles.
STATISTICAL ANALYSES: ANOVA or Kruskal-Wallis tests. RESULTS: Echocardiogram
showed that LV diastolic (Sham 8.73+/-0.57; AS 8.30+/-1.10; AS-SPR 9.19+/-1.15mm)
and systolic (Sham 4.57+/-0.67; AS 3.61+/-1.49; AS-SPR 4.62+/-1.48mm) diameters,
left atrial diameter (Sham 5.80+/-0.44; AS 7.15+/-1.22; AS-SPR 8.02+/-1.17mm),
and LV mass were higher in AS-SPR than AS. Posterior wall shortening velocity
(Sham 38.5+/-3.8; AS 35.6+/-5.6; AS-SPR 31.1+/-3.8mm/s) was lower in AS-SPR than
Sham and AS; E/A ratio was higher in AS-SPR than Sham. Developed tension was
lower in AS and AS-SPR than Sham. Time to peak tension was higher in AS-SPR than
Sham and AS after post-rest contraction. Right ventricle weight was higher in AS
SPR than AS, suggesting more severe heart failure in AS-SPR than AS. Interstitial
collagen fractional area and myocardial hydroxyproline concentration were higher
in AS than Sham. Metalloproteinase-2 and -9 activity, evaluated by zymography,
did not differ between groups. CONCLUSION: Early spironolactone administration
causes further hypertrophy in cardiac chambers, and left ventricular dilation and
dysfunction in rats with AS-induced chronic pressure overload.
PMID- 27513654
TI - Embolic stroke and after-admission atrial fibrillation.
AB - BACKGROUND: Although atrial fibrillation (AF) is a leading cause of recurrent
embolic stroke, secondary AF after stroke has been reported frequently. Because
of the different treatment each uses, it is important to detect the exact stroke
etiology. OBJECTIVES: The aim of this study was to compare the embolic stroke in
patients with known AF and after-admission AF (AAAF). METHODS: Between October
2002 and July 2009, those who were diagnosed with AF (n=354) were enrolled in our
study out of a total of 2026 acute ischemic stroke (IS) patients. The embolic
lesion patterns were assessed by two stroke specialists who were blinded to the
clinical information. RESULTS: Among 354 IS patients with AF, the number of
patients with embolic stroke was 314. Patients with embolic stroke were younger
and more likely to have larger left atrial (LA)/Aortic diameter ratio.
Approximately 90.4% of those with known AF had embolic stroke, while <60% of
patients with AAAF had embolic stroke. Nevertheless, anticoagulants were
prescribed similarly in both groups at discharge. The LA/Aortic diameter
ratio<1.5 was significantly related to AAAF. After adjusting for multiple co
variables, compared to the patients with known AF, patients with AAAF had reduced
risk of embolic stroke (Odds ratio 0.11, 95% Confidence interval 0.03-0.36, p
value<0.001). CONCLUSIONS: Compared to AAAF after stroke, known AF was associated
with embolic stroke. Therefore, we suggest that stroke etiology and some novel
echocardiographic indicators such as LA enlargement might be contemplated before
routine using of anticoagulants in IS patients with AF.
PMID- 27513655
TI - Potential beneficial effect of some adipokines positively correlated with the
adipose tissue content on the cardiovascular system.
AB - Obesity is a risk factor of cardiovascular diseases. However, in the case of
heart failure, obese and overweight patients have a more favourable prognosis
compared to patients who have a normal body weight. This phenomenon is referred
to as the "obesity paradox," and it is explained by, among others, a positive
effect of adipokines produced by adipose tissue, particularly by the tissue
located in the direct vicinity of the heart and blood vessels. The favourable
effect on the cardiovascular system is mostly associated with adiponectin and
omentin, but the levels of these substances are reduced in obese patients. Among
the adipokines which levels are positively correlated with the adipose tissue
content, favourable activity is demonstrated by apelin, progranulin, chemerin,
TNF-alpha (tumour necrosis factor-)alpha, CTRP-3 (C1q/tumour necrosis factor
(TNF) related protein), leptin, visfatin and vaspin. This activity is associated
with the promotion of regeneration processes in the damaged myocardium, formation
of new blood vessels, reduction of the afterload, improvement of metabolic
processes in cardiomyocytes and myocardial contractile function, inhibition of
apoptosis and fibrosis of the myocardium, as well as anti-inflammatory and anti
atheromatous effects. The potential use of these properties in the treatment of
heart failure and ischaemic heart disease, as well as in pulmonary hypertension,
arterial hypertension and the limitation of the loss of cardiomyocytes during
cardioplegia-requiring cardiosurgical procedures, is studied. The most advanced
studies focus on analogues of apelin and progranulin.
PMID- 27513656
TI - Frailty predicts major bleeding within 30days in elderly patients with Acute
Coronary Syndrome.
AB - OBJECTIVE: Bleeding in ACS patients is an independent marker of adverse outcomes.
Its prognostic impact is even worse in elderly population. Current bleeding risk
scores include chronological age but do not consider biologic vulnerability. No
studies have assessed the effect of frailty on major bleeding. The aim of this
study is to determine whether frailty status increases bleeding risk in patients
with ACS. METHODS: This prospective and observational study included patients
aged >=75years admitted due to type 1 myocardial infarction. Exclusion criteria
were severe cognitive impairment, impossibility to measure handgrip strength,
cardiogenic shock and limited life expectancy due to oncologic diseases. The
primary endpoint was 30-day major bleeding defined as a decrease of >=3g/dl of
haemoglobin or need of transfusion. RESULTS: A total of 190 patients were
included. Frail patients (72, 37.9%) were older, with higher comorbidity features
and with a higher CRUSADE score at admission. On univariate analysis, frailty
predicted major bleeding during 30-day follow-up despite less frequent use of a
P2Y12 inhibitor (66.2% vs 83.6%, p=0.007) and decreased catheterisation rate
(69.4% vs 94.1%, p<0.001). Major bleeding was associated with increased all-cause
mortality at day 30 (18.2% vs 2.5%, p<0.001). On multivariate analysis, frailty
was an independent predictor for major bleeding. CONCLUSION: Frailty phenotype,
as a marker of biological vulnerability, is an independent predictor of major
bleeding in elderly patients with ACS. Frailty can play an important role in
bleeding risk stratification and objective indices should be integrated into
routine initial evaluation of these patients.
PMID- 27513657
TI - Prognosis of heart failure with preserved ejection fraction treated with beta
blockers: A propensity matched study in the community.
AB - BACKGROUND: The effect of treatment with beta-blockers on the prognosis of
patients newly diagnosed with heart failure with preserved ejection fraction
(HFpEF) is unknown. OBJECTIVE: To analyze the relationship of commencing
treatment with the beta-blockers bisoprolol or carvedilol (CT-betaB) with the
prognosis of newly diagnosed HFpEF. METHODS: Prospective study over 10years on
2704 patients with HFpEF. Main outcomes were mortality (all-cause and
cardiovascular), hospitalizations for HF worsening, and visits. The independent
relationship between CT-betaB and the prognosis, stratifying patients for
cardiovascular co-morbidity after propensity score-matching (985 patients CT
betaB vs. another 985 patients non-CT-betaB), was analyzed. RESULTS: During a
median follow-up of 1877.4days (interquartile range, 1-3651.2) 1600 died (81.2%),
and 1702 were hospitalized (86.4%). CT-betaB was associated with a lower risk of
mortality (all-cause: HR [CI 95%] 0.78 [0.71 to 0.85], and cardiovascular: 0.75
[0.69 to 0.82]), a lower hospitalization rate (per 100 persons-year), 15.8 vs.
19.2, and a lower 30-day readmission rate (per 100 persons-year), 4.0 vs. 5.8,
(P<0.001 in all cases), even after adjustment for the propensity to take beta
blockers or other medications, comorbidities, and other potential confounders.
These effects of CT-betaB were independent of gender, and were observed in both
patients taking high dose betaB (over the median dose) and lower dose betaB
(under or equal to the median dose). CONCLUSIONS: In this propensity matched
study, commencing treatment with bisoprolol or carvedilol, both at high and at
lower doses, is associated with an improved prognosis of patients newly diagnosed
with HFpEF.
PMID- 27513658
TI - Effects of mitral valve repair on ventricular arrhythmia in patients with mitral
valve prolapse syndrome: A report of two cases.
PMID- 27513659
TI - Analysis of the Prevalence of and Factors Associated with Hearing Loss in Korean
Adolescents.
AB - BACKGROUND: Hearing loss can lead to a number of disabilities, subsequently
reducing the quality of life. In general, hearing thresholds of adolescents are
better than adults and the elderly. However, occasionally, adolescents acquire
hearing loss for a number of reasons. In this study, our goal was to estimate the
prevalence of hearing loss in the Korean population and to investigate the
factors related to hearing thresholds in adolescents. METHODS: A cross-sectional
study was conducted using data from the Korean National Health and Nutrition
Examination Survey (KNHANES) between 2010 and 2012. We enrolled a total of 1,658
participants, ages 13 to 18 years. We investigated the prevalence of hearing loss
and the factors associated with hearing thresholds at various frequencies (0.5,
1, 2, 3, 4, and 6 KHz). RESULTS: Weighted prevalence of unilateral and bilateral
hearing loss in Korean adolescents was 2.2% and 0.4%, respectively. Weighted
prevalence of hearing thresholds >= 20 dB at speech and high frequencies were
3.1% and 5.0%, respectively, for unilateral hearing loss and 0.7% and 1.9%,
respectively, for bilateral. Age group, tympanometric data, and household income
were significantly related to unilateral or bilateral hearing thresholds >= 20 dB
at speech frequencies. Earphone use in noisy places was associated with bilateral
hearing thresholds >= 20 dB at high frequencies. CONCLUSIONS: The prevalence of
hearing loss in Korean adolescents was 2.6% using the general standard threshold
associated with hearing loss. However, the prevalence of hearing thresholds >= 20
dB for speech and high frequencies was much higher. The results from this study
provide an estimate of hearing loss in adolescents and suggest the need for early
detection and hearing preservation programs among adolescents.
PMID- 27513660
TI - Wildfire Suppression Costs for Canada under a Changing Climate.
AB - Climate-influenced changes in fire regimes in northern temperate and boreal
regions will have both ecological and economic ramifications. We examine possible
future wildfire area burned and suppression costs using a recently compiled
historical (i.e., 1980-2009) fire management cost database for Canada and several
Intergovernmental Panel on Climate Change (IPCC) climate projections. Area burned
was modelled as a function of a climate moisture index (CMI), and fire
suppression costs then estimated as a function of area burned. Future estimates
of area burned were generated from projections of the CMI under two emissions
pathways for four General Circulation Models (GCMs); these estimates were
constrained to ecologically reasonable values by incorporating a minimum fire
return interval of 20 years. Total average annual national fire management costs
are projected to increase to just under $1 billion (a 60% real increase from the
1980-2009 period) under the low greenhouse gas emissions pathway and $1.4 billion
(119% real increase from the base period) under the high emissions pathway by the
end of the century. For many provinces, annual costs that are currently
considered extreme (i.e., occur once every ten years) are projected to become
commonplace (i.e., occur once every two years or more often) as the century
progresses. It is highly likely that evaluations of current wildland fire
management paradigms will be necessary to avoid drastic and untenable cost
increases as the century progresses.
PMID- 27513661
TI - Numerical Simulation of Dry Granular Flow Impacting a Rigid Wall Using the
Discrete Element Method.
AB - This paper presents a clump model based on Discrete Element Method. The clump
model was more close to the real particle than a spherical particle. Numerical
simulations of several tests of dry granular flow impacting a rigid wall flowing
in an inclined chute have been achieved. Five clump models with different
sphericity have been used in the simulations. By comparing the simulation results
with the experimental results of normal force on the rigid wall, a clump model
with better sphericity was selected to complete the following numerical
simulation analysis and discussion. The calculation results of normal force
showed good agreement with the experimental results, which verify the
effectiveness of the clump model. Then, total normal force and bending moment of
the rigid wall and motion process of the granular flow were further analyzed.
Finally, comparison analysis of the numerical simulations using the clump model
with different grain composition was obtained. By observing normal force on the
rigid wall and distribution of particle size at the front of the rigid wall at
the final state, the effect of grain composition on the force of the rigid wall
has been revealed. It mainly showed that, with the increase of the particle size,
the peak force at the retaining wall also increase. The result can provide a
basis for the research of relevant disaster and the design of protective
structures.
PMID- 27513662
TI - Prognostic and Diagnostic Significance of SDPR-Cavin-2 in Hepatocellular
Carcinoma.
AB - BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor worldwide. Due to
the lack of early prediction marker, numerous patients were diagnosed in their
late stage. The family of cavins plays important roles in caveolae formation and
cellular processes. Cavin-2, one of the members of cavins, has been reported as a
suppresser in cancers. In this study, we have investigated its expression pattern
and clinical significance in HCC. METHODS: RT-qPCR was performed to detect the
expression of cavin-2. RESULTS: Cavin-2 was down-regulated in HCC and associated
with tumor differentiation (r=-0.275, P=0.013) and tumor-node-metastasis (TNM)
stage (r=-0.216, P=0.035). The Overall survival analysis showed that patients
with lower cavin-2 expression had a relatively poor prognosis. Meanwhile, the
multivariate analysis revealed that cavin-2 was an independent prognostic factor.
The receiver operating characteristic curve analyses indicated that plasma cavin
2 presented a high accuracy (AUC=0.727, 0.865, 0.901) for diagnosing HCC cases
from controls, hepatitis B and cirrhosis patients, respectively. Meanwhile,
plasma cavin-2 showed a high sensitivity (88.4%, 89.9%) for detecting HCC with
the serum alpha-fetoprotein (AFP) levels below 200 ng/ml from those hepatitis B
and cirrhosis cases. CONCLUSION: Our data suggested that cavin-2 might be
considered as a potential prognostic and diagnostic indicator in HCC.
PMID- 27513663
TI - Ethanol and Acetaminophen Synergistically Induce Hepatic Aggregation and TCH346
Insensitive Nuclear Translocation of GAPDH.
AB - The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signals
during cellular stress via several post-translational modifications that change
its folding properties, protein-protein interactions and sub-cellular
localization. We examined GAPDH properties in acute mouse liver injury due to
ethanol and/or acetaminophen (APAP) treatment. Synergistic robust and time
dependent nuclear accumulation and aggregation of GAPDH were observed only in
combined, but not individual, ethanol/APAP treatments. The small molecule GAPDH
targeting compound TCH346 partially attenuated liver damage possibly via
mitochondrial mechanisms, and independent of nuclear accumulation and aggregation
of GAPDH. These findings provide a novel potential mechanism for hepatotoxicity
caused by combined alcohol and acetaminophen exposure.
PMID- 27513664
TI - Predicting Trabecular Bone Stiffness from Clinical Cone-Beam CT and HR-pQCT Data;
an In Vitro Study Using Finite Element Analysis.
AB - Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by
finite element (FE) analysis from image data obtained by clinical imaging
equipment such as high resolution peripheral quantitative computed tomography (HR
pQCT). In clinical practice today, this is done in the peripheral skeleton like
the wrist and heel. In this cadaveric bone study, fourteen bone specimens from
the wrist were imaged by two dental cone beam computed tomography (CBCT) devices
and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA).
Histomorphometric measurements from micro-CT data were used as gold standard. The
image processing was done with an in-house developed code based on the automated
region growing (ARG) algorithm. Evaluation of how well stiffness (Young's modulus
E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the
CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the
micro-CT imaging data. Strong correlations were found between the clinical
machines and micro-CT regarding trabecular bone structure parameters, such as
bone volume over total volume, trabecular thickness, trabecular number and
trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the
HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2
values between 0.78 and 0.92, based on data derived through our in-house
developed code based on the ARG algorithm. These findings indicate that
clinically used CBCT may be a feasible method for clinical studies of bone
structure and mechanical properties in future osteoporosis research.
PMID- 27513665
TI - Structure of Benthic Communities along the Taiwan Latitudinal Gradient.
AB - The distribution and the structure of benthic assemblages vary with latitude.
However, few studies have described benthic communities along large latitudinal
gradients, and patterns of variation are not fully understood. Taiwan, lying
between 21.90 degrees N and 25.30 degrees N, is located at the center of the
Philippine-Japan arc and lies at the northern margin of coral reef development. A
wide range of habitats is distributed along this latitudinal gradient, from
extensive fringing coral reefs at the southern coast to non-reefal communities at
the north. In this study, we examined the structure of benthic communities around
Taiwan, by comparing its assemblages in four regions, analyzing the effects of
the latitudinal gradient, and highlighting regional characteristics. A total of
25 sites, 125 transects, and 2,625 photographs were used to analyze the benthic
communities. Scleractinian corals present an obvious gradient of increasing
diversity from north to south, whereas macro-algae diversity is higher on the
north-eastern coast. At the country scale, Taiwanese coral communities were
dominated by turf algae (49%). At the regional scale, we observed an important
heterogeneity that may be caused by local disturbances and habitat degradation
that smooths out regional differences. In this context, our observations
highlight the importance of managing local stressors responsible for reef
degradation. Overall, this study provides an important baseline upon which future
changes in benthic assemblages around Taiwan can be assessed.
PMID- 27513666
TI - Cyclic Fatigue Resistance and Force Generated by OneShape Instruments during
Curved Canal Preparation.
AB - OBJECTIVES: To evaluate the cyclic fatigue resistance and the force generated by
OneShape files during preparation of simulated curved canals. METHODS: Six
OneShape files (the test) and six ProTaper F2 files (the control) were subject to
the bending ability test. Another thirty files of each type were used to prepare
artificial canals (n = 60), which were divided into 3 groups according to
respective curvatures of the canals (30 degrees , 60 degrees , and 90 degrees ).
The numbers of cycles to fatigue (NCF) as well as the positive and negative
forces that were generated by files during canal preparation were recorded. The
scanning electron microscopy was applied to detect the fracture surfaces.
RESULTS: Compared with ProTaper F2 files, the bending loads of OneShape files
were significantly lower at deflections of 45 degrees (P < .05), 60 degrees (P <
.05) and 75 degrees (P < .01). No significant difference was found at 30 degrees
. OneShape files presented a higher NCF in both 60 degrees and 90 degrees
canals than the control (P < .01). No significant difference of NCF was found
between OneShape and ProTaper files in 30 degrees canals. During the preparation
of 30 degrees canals by both files, the negative forces were dominant. With the
increase of the curvature, more positive forces were observed. When the OneShape
Files were compared with the control, significant different forces were found at
D3 and D2 (P < .05) in 30 degrees canals, at D2 (P < .05), D1 (P < .01) and D0
(P < .01) in 60 degrees canals, and at D4 and D3 (P < .01) in 90 degrees
canals. CONCLUSIONS: OneShape files possessed a reliable flexibility and cyclic
fatigue resistance. According to the assessments of the forces generated by
files, OneShape instruments performed in a more fatigue-resistant way during
curved canal preparation, compared with the ProTaper F2 files.
PMID- 27513667
TI - A Multi-Species TaqMan PCR Assay for the Identification of Asian Gypsy Moths
(Lymantria spp.) and Other Invasive Lymantriines of Biosecurity Concern to North
America.
AB - Preventing the introduction and establishment of forest invasive alien species
(FIAS) such as the Asian gypsy moth (AGM) is a high-priority goal for countries
with extensive forest resources such as Canada. The name AGM designates a group
of closely related Lymantria species (Lepidoptera: Erebidae: Lymantriinae)
comprising two L. dispar subspecies (L. dispar asiatica, L. dispar japonica) and
three closely related Lymantria species (L. umbrosa, L. albescens, L. postalba),
all considered potential FIAS in North America. Ships entering Canadian ports are
inspected for the presence of suspicious gypsy moth eggs, but those of AGM are
impossible to distinguish from eggs of innocuous Lymantria species. To assist
regulatory agencies in their identification of these insects, we designed a suite
of TaqMan(r) assays that provide significant improvements over existing molecular
assays targeting AGM. The assays presented here can identify all three L. dispar
subspecies (including the European gypsy moth, L. dispar dispar), the three other
Lymantria species comprising the AGM complex, plus five additional Lymantria
species that pose a threat to forests in North America. The suite of assays is
built as a "molecular key" (analogous to a taxonomic key) and involves several
parallel singleplex and multiplex qPCR reactions. Each reaction uses a
combination of primers and probes designed to separate taxa through
discriminatory annealing. The success of these assays is based on the presence of
single nucleotide polymorphisms (SNPs) in the 5' region of mitochondrial
cytochrome c oxidase I (COI) or in its longer, 3' region, as well as on the
presence of an indel in the "FS1" nuclear marker, generating North American and
Asian alleles, used here to assess Asian introgression into L. dispar dispar.
These assays have the advantage of providing rapid and accurate identification of
ten Lymantria species and subspecies considered potential FIAS.
PMID- 27513668
TI - Ingenol Mebutate for Recalcitrant Chronic Actinic Cheilitis.
AB - We present the case of a healthy 76-year-old man with a whitish, hyperkeratotic
lesion of the lower lip diagnosed as actinic cheilitis (AC) previously treated
with classic red light photodynamic therapy 5 years ago. Initial treatment with
5% imiquimod cream - also with intensified application - failed. After 2 cycles
thrice daily, consecutive applications of 150 MUg/g ingenol mebutate gel at 3
weeks' interval, the lesions cleared completely. Surprisingly, no pustular or
crusting reaction or other side effect occurred contrary to expectation.
Remission was stable for 10 months, when recurrence occurred. Ingenol mebutate
proved to be a feasible and safe treatment in this otherwise refractory case of
AC.
PMID- 27513669
TI - GaAs nanowires with oxidation-proof arsenic capping for the growth of an
epitaxial shell.
AB - We propose an arsenic-capping/decapping method, allowing the growth of an
epitaxial shell around the GaAs nanowire (NW) core which is exposed to an ambient
atmosphere, and without the introduction of impurities. Self-catalyzed GaAs NW
arrays were firstly grown on Si(111) substrates by solid-source molecular beam
epitaxy. Aiming for protecting the active surface of the GaAs NW core, the
arsenic-capping/decapping method has been applied. To validate the effect of this
method, different core/shell NWs have been fabricated. Analyses highlight the
benefit of the As capping-decapping method for further epitaxial shell growth: an
epitaxial shell with a smooth surface is achieved in the case of As-capped
decapped GaAs NWs, comparable to the in situ grown GaAs/AlGaAs NWs. This As
capping method opens a way for the epitaxial growth of heterogeneous material
shells such as functional oxides using different reactors.
PMID- 27513670
TI - Opposite Cannabis-Cognition Associations in Psychotic Patients Depending on
Family History.
AB - The objective of this study is to investigate cognitive performance in a first
episode psychosis sample, when stratifying the interaction by cannabis use and
familial or non-familial psychosis. Hierarchical-regression models were used to
analyse this association in a sample of 268 first-episode psychosis patients and
237 controls. We found that cannabis use was associated with worse working
memory, regardless of family history. However, cannabis use was clearly
associated with worse cognitive performance in patients with no family history of
psychosis, in cognitive domains including verbal memory, executive function and
global cognitive index, whereas cannabis users with a family history of psychosis
performed better in these domains. The main finding of the study is that there is
an interaction between cannabis use and a family history of psychosis in the
areas of verbal memory, executive function and global cognition: that is,
cannabis use is associated with a better performance in patients with a family
history of psychosis and a worse performance in those with no family history of
psychosis. In order to confirm this hypothesis, future research should explore
the actual expression of the endocannabinoid system in patients with and without
a family history of psychosis.
PMID- 27513671
TI - Feasibility and Outcome of a Short-Term Group Therapy for Inpatients with
Comorbid Substance Use Disorders and Depression: The InterPersonal Kiesler-Circle
Training (IPKCT).
PMID- 27513673
TI - Maximum Urine Flow Rate of Less than 15ml/Sec Increasing Risk of Urine Retention
and Prostate Surgery among Patients with Alpha-1 Blockers: A 10-Year Follow Up
Study.
AB - BACKGROUND: The aim of this study was to determine the subsequent risk of acute
urine retention and prostate surgery in patients receiving alpha-1 blockers
treatment and having a maximum urinary flow rate of less than 15ml/sec. METHODS:
We identified patients who were diagnosed with benign prostate hyperplasia (BPH)
and had a maximum uroflow rate of less than 15ml/sec between 1 January, 2002 to
31 December, 2011 from Taiwan's National Health Insurance Research Database into
study group (n = 303). The control cohort included four BPH/LUTS patients without
5ARI used for each study group, randomly selected from the same dataset (n =
1,212). Each patient was monitored to identify those who subsequently developed
prostate surgery and acute urine retention. RESULTS: Prostate surgery and acute
urine retention are detected in 5.9% of control group and 8.3% of study group
during 10-year follow up. Compared with the control group, there was increase in
the risk of prostate surgery and acute urine retention in the study group (HR =
1.83, 95% CI: 1.16 to 2.91) after adjusting for age, comorbidities, geographic
region and socioeconomic status. CONCLUSIONS: Maximum urine flow rate of less
than 15ml/sec is a risk factor of urinary retention and subsequent prostate
surgery in BPH patients receiving alpha-1 blocker therapy. This result can
provide a reference for clinicians.
PMID- 27513675
TI - Preventive Cardiovascular Nurses Association News.
PMID- 27513674
TI - Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option
for Gastroenteropancreatic Neuroendocrine Tumor Disease.
AB - BACKGROUND: The characteristic clinical heterogeneity and mostly slow-growing
behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause
problems in finding appropriate treatments. Thus, the current therapy options are
not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and
mTORC1/C2. AIM: We assessed the effects of PKI-587 in different GEP-NEN tumor
models, including the poorly differentiated cell line LCC-18, and compared them
with those of the established mTORC1 inhibitor everolimus. METHODS: We treated
BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the
inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We
assessed the impact of the treatments on viability (WST-1 assay), on apoptotic
processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow
cytometry). We determined alterations in signaling mediators by phosphor-specific
Western blot analysis and conducted multiplexed gene expression analysis
(nCounter(r) technology). RESULTS: In all cell lines, PKI-587 dose-dependently
inhibited proliferation, whereas everolimus was less effective. Treatment with
PKI-587 led to cell cycle arrest and induction of apoptosis and successfully
suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for
tumor genesis only partially inhibited by everolimus. Gene expression analyses
revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after
treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F
signaling regarding cell cycle control and apoptosis are extensively discussed in
this paper. CONCLUSION: PI3K/mTOR dual targeting is a promising new therapeutic
approach in neuroendocrine tumor disease that should be evaluated in further
clinical trials.
PMID- 27513676
TI - Reducing Disparities in Heart Disease Treatment and Outcomes Among Women: A Call
to Action.
PMID- 27513677
TI - 20 Things You Didn't Know About Exercise.
PMID- 27513678
TI - The Impact of Breakthrough Therapy Designation on Development Strategies and
Timelines for Nononcology Drugs and Vaccines.
AB - The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA,
2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to
expedite development of medicines to treat serious or life-threatening diseases.
The majority of BTDs have gone to oncology drugs, and a recent publication by
Shea et al.1 reviewed the impact of BTD on oncology drug development. This
article reviews the impact of BTD on development strategies and timelines for
nononcology drugs.
PMID- 27513679
TI - Associations of Circulating PYY3-36 Concentrations with Metabolic Syndrome in
Extremely Obese Subjects.
AB - BACKGROUND: The gut hormone peptide YY3-36 (PYY3-36) plays major roles in
regulation of appetite and energy metabolism, mediates beneficial effects of
bariatric surgery, and may be a potential weight-reducing and glucose-modulating
therapy. Obesity may influence the metabolic expression of circulating PYY3-36
and metabolic markers. We studied the relationship of PYY3-36 concentrations with
metabolic syndrome (MetSyn) components, lipids, insulin resistance, and
inflammatory biomarkers in subjects with extreme obesity. METHODS: We measured
MetSyn components and PYY3-36, lipids, hormones, homeostasis model assessment
(HOMA) index, and inflammatory biomarkers in consecutively referred patients (180
women and 111 men) aged 18-78 years with body mass index (BMI) >=40 kg/m2.
Associations of PYY3-36 to components, insulin resistance, and biomarkers were
examined with partial correlations and linear regression. RESULTS: PYY3-36
concentrations were not related to MetSyn components, HOMA index, or to
inflammatory biomarker or leptin concentrations. PYY3-36 concentrations
correlated with systolic blood pressure (r = 0.21; P < 0.0001) after adjustment
for age and gender. In linear regression analysis, PYY3-36 concentrations were
associated with systolic blood pressure after adjustment for age, gender, and
central obesity in the entire sample (Beta 0.21; 95% CI 0.09-0.34) as well as in
subjects not taking blood pressure-lowering medication (Beta 0.19; 95% CI 0.04
0.36). These associations were not statistically significant in the small subset
of participants (22%) with type 2 diabetes. CONCLUSIONS: In extremely obese
patients, fasting PYY3-36 concentrations were linked to systolic blood pressure,
but not to other components of MetSyn, suggesting divergence between pathways of
blood pressure and glucose/body weight regulation. However, this finding will
need to be further investigated.
PMID- 27513681
TI - Individual deals within teams: Investigating the role of relative i-deals for
employee performance.
AB - The authors extend i-deals theory to an individual-within-a-team context. Drawing
upon social comparison theory, they contend that individuals will react to their
own i-deals within the context of group members' i-deals. Therefore, they examine
the role of relative i-deals (an individual's i-deals relative to the team's
average) in relation to employee performance. Furthermore, integrating social
comparison theory with social identity theory the authors assert that the
behavioral outcomes of relative i-deals are influenced by the team's social and
structural attributes of team orientation and task interdependence. Finally, they
contend that the perceptions of one's relative standing with the leader, or
leader-member exchange social comparison (LMXSC), mediate the i-deals-outcome
relationship in groups with low team orientation and task interdependence.
Results of multilevel modeling using time-lagged data from 321 employees nested
in 46 teams demonstrated that the positive relationship between relative i-deals
and employee performance was stronger in groups with low team orientation and
task interdependence, and the mediation effect of LMXSC was stronger in teams
with low rather than high team orientation. (PsycINFO Database Record
PMID- 27513680
TI - Effects of Simazine Exposure on Neuronal Development-Related Factors in MN9D
Cells.
AB - BACKGROUND Simazine is a triazine herbicide used worldwide in both agricultural
and non-agricultural fields that is frequently detected in surface water and
groundwater. Due to its widespread use, an increasing amount of research has
focused on the potentially serious environmental and health risks. MATERIAL AND
METHODS We used Western blotting and real-time quantitative PCR to analyze the
effects of simazine on dopamine neuronal development-related factors in MN9D
dopaminergic cells. RESULTS The expression of tyrosine hydroxylase (TH) mRNA was
significantly increased after treatment with 300 and 600 MUmol L-1 simazine after
24 and 48 h. Levels of nuclear-related receptor 1 (Nurr1) mRNA after 24- and 48-h
exposure were decreased with 50 MUmol L-1 simazine, but increased with 600 MUmol
L-1 simazine. Significant increases in TH and Nurr1 protein were observed in all
simazine-treated groups at 24 and 48 h. The expression of neurogenin 2 and LIM
homeobox transcription factor 1 beta (Lmx1b) mRNA were significantly increased
after exposure to 600 MUmol L-1 simazine for 48 h, while the expression of
wingless-type MMTV integration site family member 1 (Wnt1) mRNA was increased by
all doses of simazine. CONCLUSIONS Simazine may have an impact on TH in MN9D
cells through 2 mechanisms; one mechanism is through the Lmx1a/Ngn2 pathway, and
the other mechanism is through the Lmx1b-pitx3/Wnt1-Nurr1 pathway. These 2
pathways likely do not operate in isolation, but rather together, during the
cellular response to simazine exposure.
PMID- 27513682
TI - Gingival crevicular fluid and saliva stress hormone levels in patients with
chronic and aggressive periodontitis.
AB - AIM: This cross-sectional study aims to analyse cortisol and
dehydroepiandrosterone (DHEA) levels in gingival crevicular fluid (GCF) and
saliva in generalized aggressive periodontitis (GAP) and generalized chronic
periodontitis (GCP) patients, as well as in periodontally healthy individuals
(C). MATERIAL AND METHODS: A total of 92 patients (31 C, 34 GCP and 27 GAP) were
included in the study. Clinical parameters including plaque index, gingival
index, bleeding on probing, probing depth and clinical attachment level;
psychosocial measurements including Beck depression inventory and state-trait
anxiety inventory; and hormone levels in GCF and saliva including cortisol and
DHEA were evaluated. RESULTS: Gingival crevicular fluid cortisol and GCF/saliva
DHEA values were significantly higher in the GAP group when compared to the other
two groups (p < 0.05). The lowest values were in the C group and the difference
between the GCP and GAP groups was statistically significant (p < 0.05). Salivary
cortisol levels were comparable for the GAP and GCP groups (p > 0.05), and the C
group had the lowest values in comparison with the other two groups (p < 0.05).
CONCLUSIONS: Within the limits of this study, salivary/GCF cortisol and DHEA
levels were suggested to be related with more severe and aggressive forms of
periodontal disease.
PMID- 27513683
TI - Structural transformation of synthetic hydroxyapatite under simulated in vivo
conditions studied with ATR-FTIR spectroscopic imaging.
AB - Hydroxyapatite and carbonate-substituted hydroxyapatite are widely used in bone
tissue engineering and regenerative medicine. Both apatite materials were
embedded into recently developed ceramic/polymer composites, subjected to
Simulated Body Fluid (SBF) for 30days and characterized using ATR-FTIR
spectroscopic imaging to assess their behaviour and structures. The specific aim
was to detect the transition phases between both types of hydroxyapatite during
the test and to analyze the surface modification caused by SBF. ATR-FTIR
spectroscopic imaging was successfully applied to characterise changes in the
hydroxyapatite lattice due to the elastic properties of the scaffolds. It was
observed that SBF treatment caused a replacement of phosphates in the lattice of
non-substituted hydroxyapatite by carbonate ions. A detailed study excluded the
formation of pure A type carbonate apatite. In turn, CO32- content in synthetic
carbonate-substituted hydroxyapatite decreased. The usefulness of ATR-FTIR
spectroscopic imaging studies in the evaluation of elastic and porous beta-glucan
hydroxyapatite composites has been demonstrated.
PMID- 27513684
TI - Sensitive detection of maltose and glucose based on dual enzyme-displayed
bacteria electrochemical biosensor.
AB - Glucoamylase-displayed bacteria (GA-bacteria) and glucose dehydrogenase-displayed
bacteria (GDH-bacteria) were co-immobilized on multi-walled carbon nanotubes
(MWNTs) modified glassy carbon electrode (GCE) to construct GA-bacteria/GDH
bacteria/MWNTs/GCE biosensor. The biosensor was developed by optimizing the
loading amount and the ratio of GA-bacteria to GDH-bacteria. The as-prepared
biosensor exhibited a wide dynamic range of 0.2-10mM and a low detection limit of
0.1mM maltose (S/N=3). The biosensor also had a linear response to glucose in the
range of 0.1-2.0mM and a low detection limit of 0.04mM glucose (S/N=3).
Interestingly, at the same concentration, glucose was 3.75-fold sensitive than
that of maltose at the proposed biosensor. No interferences were observed for
other possible mono- and disaccharides. The biosensor also demonstrated good long
term storage stability and repeatability. Further, using both GDH
bacteria/MWNTs/GCE biosensor and GA-bacteria/GDH-bacteria/MWNTs/GCE biosensor,
glucose and maltose in real samples can be detected. Therefore, the proposed
biosensor is capable of monitoring the food manufacturing and fermentation
process.
PMID- 27513685
TI - Heterogeneous Nucleation and Growth of Nanoparticles at Environmental Interfaces.
AB - Mineral nucleation is a phase transformation of aqueous components to solids with
an accompanying creation of new surfaces. In this evolutional, yet elusive,
process, nuclei often form at environmental interfaces, which provide remarkably
reactive sites for heterogeneous nucleation and growth. Naturally occurring
nucleation processes significantly contribute to the biogeochemical cycles of
important components in the Earth's crust, such as iron and manganese oxide
minerals and calcium carbonate. However, in recent decades, these cycles have
been significantly altered by anthropogenic activities, which affect the aqueous
chemistry and equilibrium of both surface and subsurface systems. These
alterations can trigger the dissolution of existing minerals and formation of new
nanoparticles (i.e., nucleation and growth) and consequently change the porosity
and permeability of geomedia in subsurface environments. Newly formed
nanoparticles can also actively interact with components in natural and
engineered aquatic systems, including those posing a significant hazard such as
arsenic. These interactions can bilaterally influence the fate and transport of
both newly formed nanoparticles and aqueous components. Due to their importance
in natural and engineered processes, heterogeneous nucleation at environmental
interfaces has started to receive more attention. However, a lack of time
resolved in situ analyses makes the evaluation of heterogeneous nucleation
challenging because the physicochemical properties of both the nuclei and
surfaces significantly and dynamically change with time and aqueous chemistry.
This Account reviews our in situ kinetic studies of the heterogeneous nucleation
and growth behaviors of iron(III) (hydr)oxide, calcium carbonate, and manganese
(hydr)oxide minerals in aqueous systems. In particular, we utilized simultaneous
small-angle and grazing incidence small-angle X-ray scattering (SAXS/GISAXS) to
investigate in situ and in real-time the effects of water chemistry and substrate
identity on heterogeneously and homogeneously formed nanoscale precipitate size
dimensions and total particle volume. Using this technique, we also provided a
new platform for quantitatively comparing between heterogeneous and homogeneous
nucleation and growth of nanoparticles and obtaining undiscovered interfacial
energies between nuclei and surfaces. In addition, nanoscale surface
characterization tools, such as in situ atomic force microscopy (AFM), were
utilized to support and complement our findings. With these powerful nanoscale
tools, we systematically evaluated the influences of environmentally abundant
(oxy)anions and cations and the properties of environmental surfaces, such as
surface charge and hydrophobicity. The findings, significantly enhanced by in
situ observations, can lead to a more accurate prediction of the behaviors of
nanoparticles in the environment and enable better control of the physicochemical
properties of nanoparticles in engineered systems, such as catalytic reactions
and energy storage.
PMID- 27513687
TI - Poor Adherence to Lung-Protective Mechanical Ventilation in Pediatric Acute
Respiratory Distress Syndrome.
AB - OBJECTIVES: To determine the frequency of low-tidal volume ventilation in
pediatric acute respiratory distress syndrome and assess if any demographic or
clinical factors improve low-tidal volume ventilation adherence. DESIGN:
Descriptive post hoc analysis of four multicenter pediatric acute respiratory
distress syndrome studies. SETTING: Twenty-six academic PICU. PATIENTS: Three
hundred fifteen pediatric acute respiratory distress syndrome patients.
MEASUREMENTS AND MAIN RESULTS: All patients who received conventional mechanical
ventilation at hours 0 and 24 of pediatric acute respiratory distress syndrome
who had data to calculate ideal body weight were included. Two cutoff points for
low-tidal volume ventilation were assessed: less than or equal to 6.5 mL/kg of
ideal body weight and less than or equal to 8 mL/kg of ideal body weight. Of 555
patients, we excluded 240 for other respiratory support modes or missing data.
The remaining 315 patients had a median PaO2-to-FIO2 ratio of 140 (interquartile
range, 90-201), and there were no differences in demographics between those who
did and did not receive low-tidal volume ventilation. With tidal volume cutoff of
less than or equal to 6.5 mL/kg of ideal body weight, the adherence rate was 32%
at hour 0 and 33% at hour 24. A low-tidal volume ventilation cutoff of tidal
volume less than or equal to 8 mL/kg of ideal body weight resulted in an
adherence rate of 58% at hour 0 and 60% at hour 24. Low-tidal volume ventilation
use was no different by severity of pediatric acute respiratory distress syndrome
nor did adherence improve over time. At hour 0, overweight children were less
likely to receive low-tidal volume ventilation less than or equal to 6.5 mL/kg
ideal body weight (11% overweight vs 38% nonoverweight; p = 0.02); no difference
was noted by hour 24. Furthermore, in the overweight group, using admission
weight instead of ideal body weight resulted in misclassification of up to 14% of
patients as receiving low-tidal volume ventilation when they actually were not.
CONCLUSIONS: Low-tidal volume ventilation is underused in the first 24 hours of
pediatric acute respiratory distress syndrome. Age, Pediatric Risk of Mortality
III, and pediatric acute respiratory distress syndrome severity were not
associated with improved low-tidal volume ventilation adherence nor did adherence
improve over time. Overweight children were less likely to receive low-tidal
volume ventilation strategies in the first day of illness.
PMID- 27513688
TI - Pharmacodynamics and Pharmacokinetics of Morphine After Cardiac Surgery in
Children With and Without Down Syndrome.
AB - OBJECTIVE: To compare the pharmacodynamics and pharmacokinetics of IV morphine
after cardiac surgery in two groups of children-those with and without Down
syndrome. DESIGN: Prospective, single-center observational trial. SETTING: PICU
in a university-affiliated pediatric teaching hospital. PATIENTS: Twenty-one
children with Down syndrome and 17 without, 3-36 months old, scheduled for
cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: A loading dose of
morphine (100 MUg/kg) was administered after coming off bypass; thereafter,
morphine infusion was commenced at 40 MUg/kg/hr. During intensive care, nurses
regularly assessed pain and discomfort with validated observational instruments
(COMFORT-Behavior scale and Numeric Rating Scale-for pain). These scores guided
analgesic and sedative treatment. Plasma samples were obtained for
pharmacokinetic analysis. MEASUREMENTS AND MAIN RESULTS: Median COMFORT-Behavior
and Numeric Rating Scale scores were not statistically significantly different
between the two groups. The median morphine infusion rate during the first 24
hours after surgery was 31.3 MUg/kg/hr (interquartile range, 23.4-36.4) in the
Down syndrome group versus 31.7 MUg/kg/hr (interquartile range, 25.1-36.1) in the
control group (p = 1.00). Population pharmacokinetic analysis revealed no
statistically significant differences in any of the pharmacokinetic variables of
morphine between the children with and without Down syndrome. CONCLUSIONS: This
prospective trial showed that there are no differences in pharmacokinetics or
pharmacodynamics between children with and without Down syndrome if pain and
distress management is titrated to effect based on outcomes of validated
assessment instruments. We have no evidence to adjust morphine dosing after
cardiac surgery in children with Down syndrome.
PMID- 27513689
TI - Is early inflammation good or bad? Linking early immune changes to hypertrophic
scarring.
PMID- 27513690
TI - Cucurbit[8]uril Regulated Activatable Supramolecular Photosensitizer for Targeted
Cancer Imaging and Photodynamic Therapy.
AB - Activatable photosensitizers (aPSs) have emerged as promising photodynamic
therapy (PDT) agents for simultaneous imaging and selective ablation of cancer.
However, traditional synthetic aPSs are limited by complex design and tedious
synthesis. Here, aPS regulated by cucurbit[8]uril (CB[8]) for targeted cancer
imaging and PDT is reported. This system is based on the host-guest interaction
between biotinylated toluidine blue (TB-B) and CB[8] to form 2TB-B@CB[8].
Moreover, a facile strategy to turn off/on the fluorescence and photodynamic
activity of TB-B is developed through the reversible assembly/disassembly of 2TB
B@CB[8]. This established system can achieve selective accumulation in tumor,
light-up cancer imaging, and enhanced anticancer behavior. Therefore, this work
provides a novel and promising strategy for the aPS build via simple and facile
regulation of supramolecular chemistry.
PMID- 27513691
TI - Association of BRCA1 Mutations with Impaired Ovarian Reserve: Connection Between
Infertility and Breast/Ovarian Cancer Risk.
AB - PURPOSE: Mutations in the BRCA1/2 genes are associated with breast and ovarian
cancer susceptibility. Recent studies have suggested that the BRCA mutation might
be associated with occult primary ovarian insufficiency. To evaluate fertility,
several studies have validated anti-Mullerian hormone (AMH) as a direct biomarker
for ovarian aging and it is considered a quantitative marker of ovarian reserve.
We hypothesize that BRCA1 gene mutations will be negatively associated with AMH
levels. METHODS: We evaluated 124 women aged 18-45 years participating in the
Northwestern Ovarian Cancer Early Detection and Prevention Program. Patients with
a history of cancer, ovarian surgery, or exposure to chemotherapy were excluded.
Linear and logistic regression modeling were performed to evaluate the
association between AMH levels, age, and BRCA1 mutation. In logistic models, the
outcome 'low AMH' was defined as AMH <0.05 ng/mL. Logistic regression models were
used to adjust for other factors, including body mass index (BMI), duration of
birth control (BC), smoking, gravidity, and parity. RESULTS: Women with the BRCA1
mutation had a significant decline in AMH with age (p = 0.0011). BRCA1-positive
women >35 years had 10 times the odds of a low AMH (<0.5 ng/mL) compared with
women <=35 years. With adjustment for BMI, duration of BC, smoking, gravidity,
parity, and age >35, BRCA1 was still strongly associated with a low AMH (p =
0.037). CONCLUSION: Women >35 with the BRCA1 mutation have a lower AMH, and hence
ovarian reserve, than women without a BRCA mutation. Therefore, young adults with
the BRCA1 mutation should be counseled regarding this potential decrease in
ovarian reserve.
PMID- 27513692
TI - Coagulation and non-coagulation effects of thrombin.
AB - Thrombin is a multifunctional serine protease produced from prothrombin, and is a
key regulator in hemostatic and non-hemostatic processes. It is the main effector
protease in primary hemostasis by activating platelets, and plays a key role in
secondary hemostasis. Besides its well-known functions in hemostasis, thrombin
also plays a role in various non-hemostatic biological and pathophysiologic
processes, predominantly mediated through activation of protease-activated
receptors (PARs). Depending on several factors, such as the concentration of
thrombin, the duration of activation, the location of PARs, the presence of
coreceptors, and the formation of PAR heterodimers, activation of the receptor by
thrombin can induce different cellular responses. Moreover, thrombin can have
opposing effects in the same cell; it can induce both inflammatory and anti
inflammatory signals. Owing to the complexity of thrombin's signal transduction
pathways, the exact mechanism behind the dichotomy of thrombin is yet still
unknown. In this review, we highlight the hemostatic and non-hemostatic functions
of thrombin, and specifically focus on the non-hemostatic dual role of thrombin
under various conditions and in relation to cardiovascular disease.
PMID- 27513694
TI - Coinage Metal Pyrazolates [(3,5-(CF3)2Pz)M]3 (M = Au, Ag, Cu) as Buckycatchers.
AB - The synthesis and characterization of supramolecular assemblies
{C60[M3]4}infinity consisting of C60 and coinage metal pyrazolates [M3] (i.e.,
[(3,5-(CF3)2Pz)M]3, where Pz = pyrazolate and M = Au, Ag, and Cu) are reported.
{C60[Cu3]4}infinity, {C60[Ag3]4}infinity and {C60[Au3]4}infinity form isomorphous
crystals. The [M3] moieties adopt a concave conformation to complement the convex
C60 surface. They exist as dimers of trimers (i.e., hexanuclear [M3]2 units) that
are held together by three close M...M metallophilic interactions at 3.1580(17),
3.2046(7), and 3.2631(7) A for copper, silver, and gold systems, respectively.
The [M3]2 moieties surround each C60 in a tetrahedral fashion, while each [M3]2
is sandwiched by two C60 molecules to form a supramolecular 3D assembly.
PMID- 27513693
TI - Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor
internalization and regulates receptor replenishment in an agonist-biased manner.
AB - Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1 R)
distal C-terminus-associated protein that modulates CB1 R signaling via G
proteins, and CB1 R down-regulation but not desensitization (Blume et al. [2015]
Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In
this study, we determined the involvement of CRIP1a in CB1 R plasma membrane
trafficking. To follow the effects of agonists and antagonists on cell surface
CB1 Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2,
which endogenously expresses both CB1 R and CRIP1a, and exhibits a well
characterized endocannabinoid signaling system. We developed stable CRIP1a-over
expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose
effects of CRIP1a on CB1 R plasma membrane expression. Results indicate that
CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1 R by a dynamin- and
clathrin-dependent process, and this was attenuated by CRIP1a over-expression.
CP55940-mediated cell surface CB1 R loss was followed by a cycloheximide
sensitive recovery of surface receptors (30-120 min), suggesting the requirement
for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB1 Rs
recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did
not affect a transient rimonabant (10 nM)-mediated increase in cell surface CB1
Rs, which is postulated to be as a result of rimonabant effects on 'non-agonist
driven' internalization. These studies demonstrate a novel role for CRIP1a in
agonist-driven CB1 R cell surface regulation postulated to occur by two
mechanisms: 1) attenuating internalization that is agonist-mediated, but not that
in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking
of de novo synthesized receptor to the cell surface.
PMID- 27513695
TI - Age, Sex, Health Insurance, and Race Associated With Increased Rate of Emergent
Pediatric Gastrointestinal Procedures.
AB - OBJECTIVES: Few studies have examined the role health disparities play in
pediatric gastrointestinal (GI) procedures. We hypothesized that health disparity
factors affect whether patients undergo an emergent versus nonemergent GI
procedure. The aims were to characterize the existing pediatric population
undergoing GI procedures at our institution and assess specific risk factors
associated with emergent versus nonemergent care. METHODS: We retrospectively
reviewed the medical records of 2110 patients undergoing GI procedures from
January 2012 to December 2014. Emergent procedures were performed on an urgent
inpatient basis. All other procedures were considered nonemergent. Health
disparity factors analyzed included age, sex, insurance type, race, and language.
Logistic regression analysis identified the odds of undergoing emergent
procedures for each factor. RESULTS: Most study patients were boys (58.2%),
primarily insured by Medicaid (63.8%), white (44.0%), and spoke English (91.7%).
Ten percent of all patients had an emergent procedure. Logistic regression
analysis showed significant odds ratios (P value) for ages 18 years older (2.16,
0.003), females (0.62, 0.001), commercial insurance users (0.49, <0.0001),
African Americans (1.94, <0.0001), and other race (1.72, 0.039). CONCLUSIONS:
Health disparities in age, sex, insurance, and race appear to exist in this
pediatric population undergoing GI procedures. Patients older than 18 years,
African Americans, and other races were significantly more likely to have an
emergent procedure. Girls and commercial insurance users were significantly less
likely to have an emergent procedure. More research is necessary to understand
why these relations exist and how to establish appropriate interventions.
PMID- 27513696
TI - Normograms for the Extrahepatic Bile Duct Diameter in Children.
AB - OBJECTIVE: The normal diameter of the extrahepatic bile duct (EHD) in children
has been poorly studied. Prior studies have enrolled small subject numbers, have
studied only specific pediatric age groups, or have potential bias due to loosely
defined exclusion criteria. We sought to establish parameters for the normal
diameter of the EHD in children from birth to late adolescence, including
premature infants. METHODS: A 121/2-month institutional review board-approved,
Health Insurance Portability and Accountability Act-compliant, retrospective
chart review of all transabdominal ultrasounds performed on children (younger
than 18 years) was conducted at a single pediatric tertiary referral center.
Exclusion criteria included a past medical history of any pancreaticobiliary or
hepatology disorder. New abnormal findings related to the liver, biliary system,
or pancreas were also excluded. Recorded EHD measurements from review of the
radiology reports were compiled. Estimated mean and 95% prediction intervals of
EHD were calculated and reported for 6 nonoverlapping pediatric age groups.
RESULTS: A total of 1016 ultrasounds on unique patients were included within the
study. Estimated mean values and calculated 95% prediction intervals (in
parentheses) for the diameter of the EHD were prematurity, 0.7 (0.3-1.7) mm; 0 to
2 months, 1.0 (0.4-2.3) mm; 3 to 11 months, 1.2 (0.5-2.9) mm; 1 to 4 years, 1.4
(0.6-3.3) mm; 5 to 12 years, 1.9 (0.8-4.3) mm; 13 to 17 years, 2.3 (1.0-5.2) mm.
CONCLUSIONS: Our derived data of normal predicted parameters of the EHD diameter
in children of all age groups will help guide clinicians in identifying those
patients outside the norm that may benefit from additional testing.
PMID- 27513697
TI - Insurance Among Young Adults With Inflammatory Bowel Disease: Changes Under the
Affordable Care Act Dependent Provision.
AB - BACKGROUND: A total of 20% to 30% of patients with inflammatory bowel disease
(IBD) present before age 18 years, eventually requiring transfer to adult care.
Vulnerability during transfer may be exacerbated by loss of insurance. A
provision of the Affordable Care Act (ACA) allows young adults (YAs) to remain on
parental private insurance through age 25 years. There has been a decrease in
uninsured YAs since its implementation in 2010. Little is known about whether
insurance coverage of YAs with IBD has been affected. OBJECTIVE: The aim of the
present study was to determine whether the proportion of uninsured YAs with IBD
has changed following the implementation of extended dependent eligibility under
the ACA. METHODS: We conducted a cross-sectional analysis of hospitalized
patients with IBD, identified in the Nationwide Inpatient Sample (NIS) using
diagnostic codes, to estimate proportions of insurance coverage during the years
2006-2013. We compared 19 to 25 year olds to 2 to 18 and 26 to 35 year olds,
unaffected by the provision, to account for underlying trends. RESULTS: From 2006
to 2010, 19 to 25 year olds had the highest proportion of uninsured, peaking at
14.1% in 2010. In 2011, the proportion decreased to 10.1%, below the proportion
of uninsured 26 to 35 year olds (13.1%), remaining in this range through 2013.
Private coverage increased in 2011 for 19 to 25 year olds, remaining stable for
26 to 35 year olds. DISCUSSION: Previous research cited 5% uninsured among all
hospitalized patients with IBD. Our study indicates a higher proportion for YAs,
decreasing after the ACA. Lack of insurance increases vulnerability during
transfer but may be modifiable through policy change. Furthermore, research
should analyze the effects of Medicaid expansion and health care exchanges.
PMID- 27513698
TI - Into the Light: Reflections on Whole-Systems Research After a Case Series Finds
Reversal of Alzheimer's.
PMID- 27513699
TI - Evidence That Dry Needling Is the Intent to Bypass Regulation to Practice
Acupuncture in the United States.
PMID- 27513700
TI - Use of the Nosyl Group as a Functional Protecting Group in Applications of a
Michael/Smiles Tandem Process.
AB - Concise preparations of elaborated polycyclic and heterocyclic systems present in
natural products were obtained using the nosyl group as a functional protecting
group not only to mask the reactivity of a sensitive moiety but also to provide a
structure desired in the final target. The group is transferred to the substrate
during deprotection through a novel extension of the Truce-Smiles rearrangement
in tandem with a 1,4-addition. This strategy provides access to a ring system
laden with valuable functionalities for subsequent manipulations and can serve as
a versatile building block for the construction of more complex molecular
architectures such as indoles in a manner compatible with the concepts of green
chemistry and atom economy.
PMID- 27513701
TI - High occurrence of rhinitis symptoms in hairdressing apprentices.
AB - BACKGROUND: Little is known about the occurrence of respiratory symptoms among
hairdressing apprentices during their training. Therefore, in this study, we
examined whether hairdressing apprentices are at increased risk of rhinitis and
asthma symptoms when compared with other young adults from the general
population. METHODS: A questionnaire was completed by 504 hairdressing
apprentices and 1400 control participants from the general population with a
similar age, gender, and geographic distribution. RESULTS: The 1-year prevalence
of rhinitis symptoms was higher in hairdressing apprentices than in controls
(58.1% vs 46.6%; odds ratio, 1.59; 95% confidence interval, 1.30-1.98), and the
prevalence was higher among hairdressing apprentices in the last years of
training compared with apprentices in the first year of training (62.4% vs 41.8%,
p = 0.003). Current smoking was more common in hairdressing apprentices (28.4% vs
17.2%, p < 0.001). Asthma symptoms were equally common in the 2 groups; however,
hairdressing apprentices had a later age of onset of wheezing than did the
controls (18 years vs 14 years, p < 0.00001) and a decreased risk of wheezing
(odds ratio, 0.72; 95% confidence interval, 0.54 to 0.95) after adjusting for
smoking, education level, and degree of rurality. Bleaching products were the
most frequently reported cause of rhinitis and asthma symptoms in hairdressing
apprentices. CONCLUSIONS: Hairdressing apprentices seem to have an increased risk
of occupational rhinitis, and bleaching products are the main cause of
respiratory symptoms. In addition, our findings suggest that a healthy worker
effect exists in relation to asthma among hairdressing apprentices.
PMID- 27513702
TI - Melatonin as add-on treatment for epilepsy.
AB - BACKGROUND: This is an updated version of the original Cochrane review published
in Issue 6, 2012.Epilepsy is one of the most common chronic neurological
disorders. Despite the plethora of antiepileptic drugs (AEDs) currently
available, 30% of people continue having seizures. This group of people requires
a more aggressive treatment, since monotherapy, the first choice scheme, fails to
control seizures. Nevertheless, polytherapy often results in a number of unwanted
effects, including neurological disturbances (somnolence, ataxia, dizziness),
psychiatric and behavioural symptoms, and metabolic alteration (osteoporosis,
inducement or inhibition of hepatic enzymes, etc.). The need for better tolerated
AEDs is even more urgent in this group of people. Reports have suggested an
antiepileptic role of melatonin with a good safety profile. OBJECTIVES: To assess
the efficacy and tolerability of melatonin as add-on treatment for epilepsy.
SEARCH METHODS: For the latest update, we searched the Cochrane Epilepsy Group's
Specialized Register (12 January 2016), the Cochrane Central Register of
Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 12
January 2016), and MEDLINE (Ovid, 11 January 2016). We searched the
bibliographies of any identified study for further references. We handsearched
selected journals and conference proceedings. We applied no language
restrictions. In addition, we contacted melatonin manufacturers (i.e. Nathura)
and original investigators to identify any unpublished studies. SELECTION
CRITERIA: Randomized controlled trials; double, single, or unblinded trials;
parallel group or cross-over studies. People with epilepsy regardless of age and
gender, including children and adults with disabilities. Administration of
melatonin as add-on treatment to any AED(s) compared to add-on placebo or no add
on treatment. DATA COLLECTION AND ANALYSIS: Review authors independently selected
trials for inclusion according to pre-defined criteria, extracted relevant data,
and evaluated the methodological quality of trials. We assessed the following
outcomes: at least 50% seizure reduction, seizure freedom, adverse events, and
quality of life. MAIN RESULTS: We included six publications, with 125
participants (106 aged under 18 years). Two different comparisons were available:
melatonin versus placebo and melatonin 5 mg versus melatonin 10 mg. Despite our
primary intention, due to insufficient information on outcomes, we were unable to
perform any meta-analyses, but summarized data narratively. Four studies were
randomized, double-blind, cross-over, placebo-controlled trials and two were
randomized, double-blind, parallel, placebo-controlled trials. Only two studies
provided the exact number of seizures during the trial compared to the baseline:
none of the participants with seizures during the trial had a change in seizure
frequency compared with the baseline. Two studies systematically evaluated
adverse effects (worsening of headache was reported in a child with migraine
under melatonin treatment). Only one study systematically evaluated quality of
life, showing no statistically significant improvement in quality of life in the
add-on melatonin group. AUTHORS' CONCLUSIONS: Included studies were of poor
methodological quality, and did not systematically evaluate seizure frequency and
adverse events, so that it was impossible to summarize data in a meta-analysis.
It is not possible to draw any conclusion about the role of melatonin in reducing
seizure frequency or improving quality of life in people with epilepsy.
PMID- 27513703
TI - Surgical management of petrous apex cholesterol granulomas by an
infralabyrinthine approach: our experience with fourteen cases.
PMID- 27513705
TI - Cold Sintering: A Paradigm Shift for Processing and Integration of Ceramics.
AB - This paper describes a sintering technique for ceramics and ceramic-based
composites, using water as a transient solvent to effect densification (i.e.
sintering) at temperatures between room temperature and 200 degrees C. To
emphasize the incredible reduction in sintering temperature relative to
conventional thermal sintering this new approach is named the "Cold Sintering
Process" (CSP). Basically CSP uses a transient aqueous environment to effect
densification by a mediated dissolution-precipitation process. CSP of NaCl,
alkali molybdates and V2 O5 with small concentrations of water are described in
detail, but the process is extended and demonstrated for a diverse range of
chemistries (oxides, carbonates, bromides, fluorides, chlorides and phosphates),
multiple crystal structures, and multimaterial applications. Furthermore, the
properties of selected CSP samples are demonstrated to be essentially equivalent
as samples made by conventional thermal sintering.
PMID- 27513706
TI - The effects of air pollution on asthma hospital admissions in Adelaide, South
Australia, 2003-2013: time-series and case-crossover analyses.
AB - BACKGROUND: Air pollution can have adverse health effects on asthma sufferers,
but the effects vary with geographic, environmental and population
characteristics. There has been no long time-series study in Australia to
quantify the effects of environmental factors including pollen on asthma
hospitalizations. OBJECTIVES: This study aimed to assess the seasonal impact of
air pollutants and aeroallergens on the risk of asthma hospital admissions for
adults and children in Adelaide, South Australia. METHODS: Data on hospital
admissions, meteorological conditions, air quality and pollen counts for the
period 2003-2013 were sourced. Time-series analysis and case-crossover analysis
were used to assess the short-term effects of air pollution on asthma
hospitalizations. For the time-series analysis, generalized log-linear quasi
Poisson and negative binomial regressions were used to assess the relationships,
controlling for seasonality and long-term trends using flexible spline functions.
For the case-crossover analysis, conditional logistic regression was used to
compute the effect estimates with time-stratified referent selection strategies.
RESULTS: A total of 36,024 asthma admissions were considered. Findings indicated
that the largest effects on asthma admissions related to PM2.5 , NO2 , PM10 and
pollen were found in the cool season for children (0-17 years), with the 5-day
cumulative effects of 30.2% (95% CI: 13.4-49.6%), 12.5% (95% CI: 6.6-18.7%), 8.3%
(95% CI: 2.5-14.4%) and 4.2% (95% CI: 2.2-6.1%) increases in risk of asthma
hospital admissions per 10 unit increments, respectively. The largest effect for
ozone was found in the warm season for children with the 5-day cumulative effect
of an 11.7% (95% CI: 5.8-17.9%) increase in risk of asthma hospital admissions
per 10 ppb increment in ozone level. CONCLUSION: Findings suggest that children
are more vulnerable and the associations between exposure to air pollutants and
asthma hospitalizations tended to be stronger in the cool season compared to the
warm season, with the exception of ozone. This study has important public health
implications and provides valuable evidence for the development of policies for
asthma management.
PMID- 27513707
TI - (eta(4)-Butadiene)Sn(0) Complexes: A New Approach for Zero-Valent p-Block
Elements Utilizing a Butadiene as a 4pi-Electron Donor.
AB - Research on zero-valent p-block elements is a recent hot topic in synthetic and
theoretical chemistry because of their novel electronic states having two lone
pairs in both the s- and p-orbitals. It is considered that sigma-donating ligands
bearing large substituents are essential to stabilize these species. Herein, we
propose a new approach using butadiene as a 4pi-electron donor to stabilize zero
valent group 14 elements. During our study to explore the coordination chemistry
of stannacyclopentadienyl ligands, unexpected products, in which the tin atom is
coordinated by a butadiene in a eta(4)-fashion, were obtained. Because butadiene
is a neutral 4pi-electron donating ligand, the formal oxidation number of the tin
atoms of the products should be zero, which is supported by X-ray diffraction
analysis and theoretical calculations. A mechanism for the formation of the
products is also described.
PMID- 27513708
TI - Understanding the Early Regime of Drop Spreading.
AB - We present experimental data to characterize the spreading of a liquid drop on a
substrate kept submerged in another liquid medium. They reveal that drop
spreading always begins in a regime dominated by drop viscosity where the
spreading radius scales as r ~ t with a nonuniversal prefactor. This initial
viscous regime either lasts in its entirety or switches to an intermediate
inertial regime where the spreading radius grows with time following the well
established inertial scaling of r ~ t(1/2). This latter case depends on the
characteristic viscous length scale of the problem. In either case, the final
stage of spreading, close to equilibrium, follows Tanner's law. Further
experiments performed on the same substrate kept in ambient air reveal a similar
trend, albeit with limited spatiotemporal resolution, showing the universal
nature of the spreading behavior. It is also found that, for early times of
spreading, the process is similar to coalescence of two freely suspended liquid
drops, making the presence of the substrate and consequently the three-phase
contact line insignificant.
PMID- 27513709
TI - Spectrum of epilepsy and electroencephalogram patterns in idic (15) syndrome.
AB - Previous reports summarized the seizure types occurring in patients with idic(15)
syndrome. To better define this issue, we retrospectively analyzed the evolution
of electroencephalogram findings and seizures in 35 patients with confirmed
idic(15). Epilepsy occurred in 28 patients (80%), with a median age of onset of 3
years 3 months. The initial seizures were infantile spasms associated with a
hypsarrhythmic electroencephalogram (nine patients), focal/generalized tonic
(seven patients), or atypical absences (eight patients). High doses of oral
steroids were given in all nine children with infantile spasms, with remission of
seizures and resolution of electroencephalogram abnormalities. Among them, three
were seizure free at the time of evaluation, but six later developed Lennox
Gastaut syndrome or Lennox-Gastaut-like syndrome. The eight patients with
atypical absences developed Lennox-Gastaut syndrome or Lennox-Gastaut-like
syndrome. Epilepsy was well controlled in 32% of the patients; satisfactorily
controlled (seizures reduced >75%) in 21.4%; partially controlled (seizures
reduced <50%) in 10.7%; and uncontrolled in 32%. One patient was not taking any
anti-epileptic drugs by his parents' choice. Fourteen percent were on
monotherapy; whereas the other 82% were on polytherapy. Seizures stopped at a
median age of 5 years 5 months. The interictal electroencephalogram showed
slow/sharp waves, and/or biphasic spikes-polyspikes, spike/wave complexes, and an
excess of fast activity mainly over the fronto-temporal areas. Epilepsy is a
major clinical challenge in patients with idic(15), associated with a poor
prognosis in 55%. Frontal lobe seizures are a novel finding. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27513710
TI - Estimating healthcare costs of acute gastroenteritis and human campylobacteriosis
in Switzerland.
AB - Rising numbers of campylobacteriosis case notifications in Switzerland resulted
in an increased attention to acute gastroenteritis (AG) in general. Patients with
a laboratory-confirmed Campylobacter infection perceive their disease as severe
and around 15% of these patients are hospitalized. This study aimed at estimating
healthcare costs due to AG and campylobacteriosis in Switzerland. We used
official health statistics, data from different studies and expert opinion for
estimating individual treatment costs for patients with different illness
severity and for extrapolating overall costs due to AG and campylobacteriosis. We
estimated that total Swiss healthcare costs resulting from these diseases amount
to ?29-45 million annually. Data suggest that patients with AG consulting a
physician without a stool diagnostic test account for ?9.0-24.2 million, patients
with a negative stool test result for Campylobacter spp. for ?12.3 million,
patients testing positive for Campylobacter spp. for ?1.8 million and
hospitalized campylobacteriosis patients for ?6.5 million/year. Healthcare costs
of campylobacteriosis are high and most likely increasing in Switzerland
considering that campylobacteriosis case notifications steadily increased in the
past decade. Costs and potential cost savings for the healthcare system should be
considered when designing sectorial and cross-sectorial interventions to reduce
the burden of human campylobacteriosis in Switzerland.
PMID- 27513712
TI - Spin state switching of metal complexes by visible light or hard X-rays.
AB - Electromagnetic stimuli of spin crossover compounds restricted to UV-vis light
irradiation for many years could be recently extended to X-ray excitation. This
review covers a large variety of light-induced effects, as well as recent
analogues stimulated by X-ray irradiation which have not yet been reviewed. The
focus is also on multistable multinuclear spin crossover compounds which are the
subject of lively discussions within the spin crossover community. Their spin
transition often occurs incompletely and with different switching mechanisms. In
this review, we recall a predicted sequential switching induced thermally as well
as a concerted stimulation mechanism by light irradiation for these interesting
multifunctional materials.
PMID- 27513713
TI - Minor neurological dysfunction in five year old very preterm children is
associated with lower processing speed.
AB - BACKGROUND: Minor neurological dysfunction (MND) is present in one quarter to one
third of children born very preterm (VP). The more severe form, complex (c)-MND
has been associated with learning disabilities, behavioural and motor problems.
OBJECTIVE: To study the association between c-MND and neurocognitive and motor
disabilities at age five in VP children without CP. METHODS: Ninety-four children
born with gestational age<30weeks and/or a birth weight<1000g were assessed at
five years corrected age. MND was classified according to Touwen. The Wechsler
Preschool and Primary School Scale of Intelligence (WPPSI-III-NL) was used to
measure intelligence. Simple reaction time, focused attention and visuomotor
coordination were measured using the Amsterdam Neuropsychological Tasks, and
working memory using a Digit Span Task. For motor skills the Movement Assessment
Battery for children (M-ABC2) was used. RESULTS: Eighty-one percent was
classified as 'normal' (no or simple (s-)-MND) and 19% as 'abnormal'(c-MND or
mild CP). The abnormal group had a significantly lower processing speed quotient
(PSQ), M-ABC percentile score and slower simple Reaction Time than the normal
group. Verbal IQ, Performance IQ, working memory, focused attention and
visuomotor coordination did not differ between groups. Exclusion of the mild CP
cases (n=4) led to similar results. CONCLUSIONS: Five year old VP children with c
MND have lower PSQ, slower reaction time, and poorer motor skills, than those
without c-MND. Neurological examination should include identification of MND to
help identify children at risk for neurocognitive disabilities.
PMID- 27513714
TI - Vitamin D supplementation during pregnancy on infant anthropometric measurements
and bone mass of mother-infant pairs: A randomized placebo clinical trial.
AB - INTRODUCTION: Based on the essential role of vitamin D in the regulation of
calcium metabolism, we evaluated the effects of 2000IUvitamin D/day in late
pregnancy on infant's anthropometric measurements and bone mass parameters of
mother-infant pairs. MATERIAL AND METHODS: In this randomized clinical trial, the
main inclusion criteria were: aged 18 or older, no history of internal diseases
and pregnancy complications, and a singleton live fetus. The intervention group
received two 1000IU vitamin D3 pills (2000IU) daily from weeks 26-28 until
childbirth. Maternal serum 25-hydroxyvitamin D, infants' anthropometric
measurements (at birth, 4th and 8th weeks postnatal), and maternal and infant
bone mass parameters were examined. RESULTS: The two groups were not
statistically different in relation to baseline 25-hydroxyvitamin D
concentrations. However, there was a significant difference between the study
groups with regard to change in vitamin D status over time (p<0.001). In cross
sectional analysis, the two groups were not different with respect to
anthropometric measurements in three time points. Also, in repeated measure
analysis, the two groups did not show any statistical differences concerning the
infants' anthropometric measurements. The bone mass measurements of all the 28
mothers who belonged to the two study groups were not different. Finally, the
bones mass measurements of the infants in the two study groups were not
different. CONCLUSION: Ingestion of 2000IUvitamin D3/day during late pregnancy
did not improve anthropometric measurements of infants from birth until the 8th
week postnatal, nor improve the maternal and infant bone mass measurements.
PMID- 27513716
TI - Review of Prosthetic Joint Infection from Listeria monocytogenes.
AB - BACKGROUND: Prosthetic joint infection from Listeria monocytogenes is rare. We
decided to shed light on this illness and review the reported cases to better
understand its characteristics. PATIENTS AND METHODS: We conducted a
comprehensive review of the English literature using PubMed. We also included one
case that we had managed. RESULTS: We found 25 cases of prosthetic joint
infection from L. monocytogenes reported individually and a retrospective study
of 43 cases of joint and bone listerial infection, including 34 with prosthetic
joint infection, conducted in France. We have described their clinical and para
clinical features and tried to elaborate on the pathophysiology, treatment, and
prevention. CONCLUSION: Prosthetic joint infection from L. monocytogenes is
mainly late. Systemic inflammation may be absent. Although rare, it must be
suspected in patients at high risk for both prosthetic joint and listerial
infections. In addition, those patients must be instructed on appropriate
preventive measures.
PMID- 27513717
TI - Nuclear Magnetic Resonance Measurements and Electronic Structure of Pu(IV) in
[(Me)4N]2PuCl6.
AB - The synthesis, electronic structure, and characterization via single-crystal X
ray diffraction, nuclear magnetic resonance (NMR) spectroscopy, and magnetic
susceptibility of (Me4N)2PuCl6 are reported. NMR measurements were performed to
both search for the direct (239)Pu resonance and to obtain local magnetic and
electronic information at the Cl site through (35)Cl and (37)Cl spectra. No
signature of (239)Pu NMR was observed. The temperature dependence of the Cl
spectra was simulated by diagonalizing the Zeeman and quadrupolar Hamiltonians
for (35)Cl, (37)Cl, and (14)N isotopes. Electronic structure calculations predict
a magnetic Gamma5 triplet ground state of Pu(IV) in the crystalline electric
field of the undistorted PuCl6 octahedron. A tetragonal distortion would result
in a very small splitting (~20 cm(-1)) of the triplet ground state into a
nonmagnetic singlet and a doublet state. The Cl shifts have an inflection point
at T ~ 15 K, differing from the bulk susceptibility, indicating a nonmagnetic
crystal field ground state. The Cl spin-lattice relaxation time is constant to T
= 15 K, below which it rapidly increases, also supporting the nonmagnetic crystal
field ground state.
PMID- 27513718
TI - QuickStats: Age-Adjusted Death Rates* for Males Aged 15-44 Years, by the Five
Leading Causes of Death(?) - United States, 1999 and 2014.
AB - The age-adjusted death rate for males aged 15-44 years was 10% lower in 2014
(156.6 per 100,000 population) than in 1999 (174.1). Among the five leading
causes of death, the age-adjusted rates for three were lower in 2014 than in
1999: cancer (from 17.1 to 12.8; 25% decline), heart disease (20.1 to 17.0; 15%
decline), and homicide (15.7 to 13.8; 12% decline). The age-adjusted death rates
for two of the five causes were higher in 2014 than in 1999: suicide (20.1 to
22.5; 12% increase), and unintentional injuries (from 48.7 to 51.0; 5% increase).
PMID- 27513720
TI - Determination and correlation of lower limb anatomical parameters and bone age
during skeletal growth (based on 1005 cases).
AB - The aim of this study was to evaluate bone age and its correlation with the lower
limbs' developing skeletal anatomy during growth. 1005 children and young adults
were evaluated for bone age and 14 different parameters measured on lower-limb
reconstructions from radiological examinations carried out with an EOS 2D/3D
system in the course of routine orthopedic indicated diagnostic practice.
Cervical vertebral morphology evaluation for bone age using the Hassel-Farman
method, which describes six stages of maturity, was selected. Intra- and inter
observer reliability tests for this method, and for the EOS 3D reconstructions
were performed. Statistical analysis were performed using Spearman correlation,
multiple linear regression, and t-test. The intra- and inter-observer reliability
of the Hassel-Farman method and the EOS 3D lower-limb reconstruction were found
to be excellent. Interestingly one bone age stage could include individuals
across a 12.1 year range, and conversely individuals of the same calendar age
could be of one of 3.2 different bone age stages. In the prepubertal age groups
all six bone stages could be observed. Bone age revealed a stronger relationship,
lower standard deviations with groups and proved to be a better discriminating
variable than the calendar age by collodiaphyseal angle, femoral, and tibial
torsion, femorotibial rotation, and mechanical tibiofemoral angle. Bone age is an
indicator of skeletal maturity and may more accurately describe the growth of
some lower limb parameters. As a result we suggest the consideration of bone age
when evaluating lower-limb biomechanic-anatomical parameters. (c) 2016
Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
35:1431-1441, 2017.
PMID- 27513721
TI - Prevalence and survival benefit of adjuvant chemotherapy in stage III colon
cancer patients: Comparison of overall and age-stratified results by
multivariable modeling and propensity score methodology in a population-based
cohort.
AB - BACKGROUND: Few population-based studies have assessed the effectiveness of
adjuvant chemotherapy (ACT) in stage III colon cancer patients according to age.
We sought to quantify the prevalence of ACT use and the absolute and relative
survival benefit of ACT overall and by age in a population-based cohort. METHODS:
Stage III patients with adenocarcinoma of the colon identified by the Georgia
Comprehensive Cancer Registry for the years 2000-07 were eligible (final N=3057).
We utilized Poisson regression to obtain adjusted mortality rates (MR) and Cox
proportional hazards models to obtain adjusted hazard ratios (HRs) for 5-year
overall survival. We evaluated control of confounding by comparing HRs obtained
via multivariable modeling (MM), propensity score weighting (PSW), and propensity
score matching (PSM). RESULTS: Just over one-third of colon cancer patients did
not receive ACT, and the proportion increased with age. Overall, receipt of ACT
conferred an absolute (MR difference [No ACT rate-ACT rate] 25.4 deaths/1000
person-years [py], 95% confidence interval [CI]: 19.1-32.7 deaths/1000 py) and
relative (MM HR=0.67, 95% CI: 0.59-0.76) survival benefit. The survival benefit
was demonstrated across age groups. MM and propensity score methods yielded
highly similar HRs. CONCLUSION: Unless contraindicated, efforts to ensure receipt
of ACT for stage III colon cancer patients up to 84 years of age are needed to
improve the prognosis of patients with node-positive disease.
PMID- 27513722
TI - Burden of cancer attributable to tobacco smoking in member countries of the
Association of Southeast Asian Nations (ASEAN), 2012.
AB - BACKGROUND: Cancer is an increasing problem in ASEAN (Association of Southeast
Asian Nations). Tobacco use is a well-established risk factor for many types of
cancers. Evidence on burden of cancer attributable to tobacco is essential to
raise public and political awareness of the negative effects of tobacco on cancer
and to be used to stimulate political action aims at reducing smoking prevalence
in ASEAN member countries. The objective of this study was to estimate burden of
cancer attributable to tobacco smoking in ASEAN, 2012. METHODS: In this study,
smoking prevalence was combined with Relative Risks (RRs) of cancer to obtain
Smoking Attributable Fractions (SAFs). Cancer incidence and mortality data among
individuals aged 15 years and older were derived from GLOBOCAN 2012. Fourteen
types of cancer were included in the analysis. Sensitivity analyses were
conducted to examine the impact of the use of alternative RRs and the use of
alternative prevalence of smoking in some countries. RESULTS: The findings showed
that tobacco smoking was responsible for 131,502 cancer incidence and 105,830
cancer mortality in ASEAN countries in 2012. In other words, tobacco smoking was
accounted for 28.4% (43.3% in male and 8.5% in female) of cancer incidence and
30.5% (44.2% in male and 9.4% in female) of cancer mortality in ASEAN. When
looking at the types of cancer, lung cancer showed the strongest association with
tobacco smoking. Incidence of cancer and cancer mortality attributable to tobacco
smoking varied by countries due to the differences in size of population,
background risk of cancer, and prevalence of smoking in each country. According
to the sensitivity analyses, RRs of lung cancer, pharynx cancer, and larynx
cancer used in the estimates have significant impact on the estimates.
CONCLUSIONS: As about one-third of cancer incidence and mortality in ASEAN are
attributable to tobacco smoking ASEAN member countries are strongly encouraged to
put in place stronger tobacco control policies and to strengthen the existing
tobacco control measure in order to effectively control cancer.
PMID- 27513723
TI - Energy Gap Tuning and Carrier Dynamics in Colloidal Ge1-xSnx Quantum Dots.
AB - Optical transition energies and carrier dynamics in colloidally synthesized 2.0
+/- 0.8 nm Ge1-xSnx quantum dots (x = 0.055-0.236) having visible luminescence
were investigated using steady-state and time-resolved photoluminescence (PL)
spectroscopy supported by first-principles calculations. By changing Sn content
from x = 0.055 to 0.236, experimentally determined HOMO-LUMO gap at 15 K was
tuned from 1.88 to 1.61 eV. Considering the size and compositional variations,
these values were consistent with theoretically calculated ones. At 15 K, time
resolved PL revealed slow decay of luminescence (3-27 MUs), likely due to the
recombination of spin-forbidden dark excitons and recombination of carriers
trapped at surface states. Increasing Sn concentration to 23.6% led to 1 order of
magnitude faster recombination. At 295 K, PL decays were 3 orders of magnitude
faster (9-28 ns) owing to the thermal activation of bright excitons and carrier
detrapping from surface states.
PMID- 27513724
TI - Increasing flash droughts over China during the recent global warming hiatus.
AB - The recent global warming slowdown or hiatus after the big El Nino event in
1997/98 raises the questions of whether terrestrial hydrological cycle is being
decelerated and how do the hydrological extremes respond to the hiatus. However,
the rapidly developing drought events that are termed as "flash droughts"
accompanied by extreme heat, low soil moisture and high evapotranspiration (ET),
occurred frequently around the world, and caused devastating impacts on crop
yields and water supply. Here, we investigate the long-term trend and variability
of flash droughts over China. Flash droughts are most likely to occur over humid
and semi-humid regions, such as southern and northeastern China. Flash drought
averaged over China increased by 109% from 1979 to 2010, and the increase was
mainly due to a long term warming of temperature (50%), followed by the
contributions from decreasing soil moisture and increasing ET. There was a slight
drop in temperature after 1997, but the increasing trend of flash droughts was
tripled. Further results indicate that the decreasing temperature was compensated
by the accelerated drying trends of soil moisture and enhanced ET, leading to an
acceleration of flash droughts during the warming hiatus. The anthropogenic
warming in the next few decades may exacerbate future flash drought conditions in
China.
PMID- 27513725
TI - MicroRNA-106a suppresses proliferation, migration, and invasion of bladder cancer
cells by modulating MAPK signaling, cell cycle regulators, and Ets-1-mediated MMP
2 expression.
AB - Despite the clinical significance of tumorigenesis, little is known about the
cellular signaling networks of microRNAs (miRs). Here we report a new finding
that mir-106a regulates the proliferation, migration, and invasion of bladder
cancer cells. Basal expression levels of mir-106a were significantly lower in
bladder cancer cells than in normal urothelial cells. Overexpression of mir-106a
suppressed the proliferation of bladder cancer cell line EJ. Transient
transfection of mir-106a into EJ cells led to downregulation of ERK
phosphorylation and upregulation of p38 and JNK phosphorylation over their levels
in the control. Flow cytometry analysis revealed that mir-106a-transfected cells
accumulated in the G1-phase of the cell cycle, and cyclin D1 and CDK6 were
significantly downregulated. This G1-phase cell cycle arrest was due in part to
the upregulation of p21CIP1/WAF1. In addition, mir-106a overexpression blocked
the wound-healing migration and invasion of EJ cells. Furthermore, mir-106a
transfection resulted in decreased expression of MMP-2 and diminished binding
activity of transcription factor Ets-1 in EJ cells. Collectively, we report the
novel mir-106a-mediated molecular signaling networks that regulate the
proliferation, migration, and invasion of bladder cancer cells, suggesting that
mir-106a may be a therapeutic target for treating advanced bladder tumors.
PMID- 27513726
TI - Oil palm EgCBF3 conferred stress tolerance in transgenic tomato plants through
modulation of the ethylene signaling pathway.
AB - CBF/DREB1 is a group of transcription factors that are mainly involved in abiotic
stress tolerance in plants. They belong to the AP2/ERF superfamily of plant
specific transcription factors. A gene encoding a new member of this group was
isolated from ripening oil palm fruit and designated as EgCBF3. The oil palm
fruit demonstrates the characteristics of a climacteric fruit like tomato, in
which ethylene has a major impact on the ripening process. A transgenic approach
was used for functional characterization of the EgCBF3, using tomato as the model
plant. The effects of ectopic expression of EgCBF3 were analyzed based on
expression profiling of the ethylene biosynthesis-related genes, anti-freeze
proteins (AFPs), abiotic stress tolerance and plant growth and development. The
EgCBF3 tomatoes demonstrated altered phenotypes compared to the wild type
tomatoes. Delayed leaf senescence and flowering, increased chlorophyll content
and abnormal flowering were the consequences of overexpression of EgCBF3 in the
transgenic tomatoes. The EgCBF3 tomatoes demonstrated enhanced abiotic stress
tolerance under in vitro conditions. Further, transcript levels of ethylene
biosynthesis-related genes, including three SlACSs and two SlACOs, were altered
in the transgenic plants' leaves and roots compared to that in the wild type
tomato plant. Among the eight AFPs studied in the wounded leaves of the EgCBF3
tomato plants, transcript levels of SlOSM-L, SlNP24, SlPR5L and SlTSRF1
decreased, while expression of the other four, SlCHI3, SlPR1, SlPR-P2 and SlLAP2,
were up-regulated. These findings indicate the possible functions of EgCBF3 in
plant growth and development as a regulator of ethylene biosynthesis-related and
AFP genes, and as a stimulator of abiotic stress tolerance.
PMID- 27513727
TI - Virus Infection of Plants Alters Pollinator Preference: A Payback for Susceptible
Hosts?
AB - Plant volatiles play important roles in attraction of certain pollinators and in
host location by herbivorous insects. Virus infection induces changes in plant
volatile emission profiles, and this can make plants more attractive to insect
herbivores, such as aphids, that act as viral vectors. However, it is unknown if
virus-induced alterations in volatile production affect plant-pollinator
interactions. We found that volatiles emitted by cucumber mosaic virus (CMV)
infected tomato (Solanum lycopersicum) and Arabidopsis thaliana plants altered
the foraging behaviour of bumblebees (Bombus terrestris). Virus-induced
quantitative and qualitative changes in blends of volatile organic compounds
emitted by tomato plants were identified by gas chromatography-coupled mass
spectrometry. Experiments with a CMV mutant unable to express the 2b RNA
silencing suppressor protein and with Arabidopsis silencing mutants implicate
microRNAs in regulating emission of pollinator-perceivable volatiles. In tomato,
CMV infection made plants emit volatiles attractive to bumblebees. Bumblebees
pollinate tomato by 'buzzing' (sonicating) the flowers, which releases pollen and
enhances self-fertilization and seed production as well as pollen export. Without
buzz-pollination, CMV infection decreased seed yield, but when flowers of mock
inoculated and CMV-infected plants were buzz-pollinated, the increased seed yield
for CMV-infected plants was similar to that for mock-inoculated plants. Increased
pollinator preference can potentially increase plant reproductive success in two
ways: i) as female parents, by increasing the probability that ovules are
fertilized; ii) as male parents, by increasing pollen export. Mathematical
modeling suggested that over a wide range of conditions in the wild, these
increases to the number of offspring of infected susceptible plants resulting
from increased pollinator preference could outweigh underlying strong selection
pressures favoring pathogen resistance, allowing genes for disease susceptibility
to persist in plant populations. We speculate that enhanced pollinator service
for infected individuals in wild plant populations might provide mutual benefits
to the virus and its susceptible hosts.
PMID- 27513728
TI - Extrapolation of a non-linear autoregressive model of pulmonary mechanics.
AB - For patients with acute respiratory distress syndrome (ARDS), mechanical
ventilation (MV) is an essential therapy in the intensive care unit (ICU).
Suboptimal PEEP levels in MV can cause ventilator induced lung injury, which is
associated with increased mortality, extended ICU stay, and high cost. The
ability to predict the outcome of respiratory mechanics in response to changes in
PEEP would thus provide a critical advantage in personalising and improving care.
Testing the potentially dangerous high pressures would not be required to assess
their impact. A nonlinear autoregressive (NARX) model was used to predict airway
pressure in 19 data sets from 10 mechanically ventilated ARDS patients. Patient
specific NARX models were identified from pressure and flow data over one, two,
three, or four adjacent PEEP levels in a recruitment manoeuvre. Extrapolation of
NARX model elastance functions allowed prediction of patient responses to PEEP
changes to higher or lower pressures. NARX model predictions were more successful
than those using a well validated first order model (FOM). The most clinically
important results were for extrapolation up one PEEP step of 2cmH2O from the
highest PEEP in the training data. When the NARX model was trained on one PEEP
level, the mean RMS residual for the extrapolation PEEP level was 0.52 (90% CI:
0.47-0.57) cmH2O, compared to 1.50 (90% CI: 1.38-1.62) cmH2O for the FOM. When
trained on four PEEP levels, the NARX result was 0.50 (90% CI: 0.42-0.58) cmH2O,
and was 1.95 (90% CI: 1.71-2.19) cmH2O for the FOM. The results suggest that a
full recruitment manoeuvre may not be required for the NARX model to obtain a
useful estimate of the pressure waveform at higher PEEP levels. The methodology
could thus allow clinicians to make informed decisions about ventilator PEEP
settings while reducing the risk associated with high PEEP, and subsequent high
peak airway pressures.
PMID- 27513730
TI - Functional differences between neonatal and adult fibroblasts and keratinocytes:
Donor age affects epithelial-mesenchymal crosstalk in vitro.
AB - Clinical evidence suggests that healing is faster and almost scarless at an early
neonatal age in comparison with that in adults. In this study, the phenotypes of
neonatal and adult dermal fibroblasts and keratinocytes (nestin, smooth muscle
actin, keratin types 8, 14 and 19, and fibronectin) were compared. Furthermore,
functional assays (proliferation, migration, scratch wound closure) including
mutual epithelial-mesenchymal interactions were also performed to complete the
series of experiments. Positivity for nestin and alpha smooth muscle actin was
higher in neonatal fibroblasts (NFs) when compared with their adult counterparts
(adult fibroblasts; AFs). Although the proliferation of NFs and AFs was similar,
they significantly differed in their migration potential. The keratinocyte
experiments revealed small, poorly differentiated cells (positive for keratins 8,
14 and 19) in primary cultures isolated from neonatal tissues. Moreover, the
neonatal keratinocytes exhibited significantly faster rates of healing the
experimentally induced in vitro defects in comparison with adult cells. Notably,
the epithelial/mesenchymal interaction studies showed that NFs in co-culture with
adult keratinocytes significantly stimulated the adult epithelial cells to
acquire the phenotype of small, non-confluent cells expressing markers of poor
differentiation. These results indicate the important differences between
neonatal and adult cells that may be associated with improved wound healing
during the early neonatal period.
PMID- 27513731
TI - Hemophagocytic Lymphohistocytosis in the Chinese Han Population May Be Associated
with an STXBP2 Gene Polymorphism.
AB - STUDY PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening
disease of severe hyperinflammation caused by uncontrolled proliferation of
activated lymphocytes and macrophages. In this study, we aimed to explore the
genetic factors involved in the pathogenesis of both acquired and familial type
HLH. METHOD: The ION TORRENT semi-conductor sequencing method was used to
sequence samples from 10 patients who were diagnosed or highly suspected of HLH.
Then SNP rs2303116 of STXBP2 genotyping was performed by Sanger sequencing method
on samples from 24 patients with HLH and 182 normal controls. Genotype
frequencies were then compared and tested by multivariate logistic regression.
Finally, the potential impact of rs2303116 on splicing factor binding ability was
evaluated using the ESEfinder 3.0 online tool. RESULTS: A total of 92 variants
were identified in 10 HLH patients, of which 24 variants were rare variants
(MAF<0.01), while the remaining 68 variants were common variants (MAF>0.01).
Among them, 8 different genetic variations in the STXBP2 sequence were
identified. We focused on the synonymous SNP rs2303116, as 30% of patients had
CT/TT genotype. SNP genotyping was further performed on 24 HLH patients and 182
healthy control cohorts, and the results indicated a significantly elevated CT/TT
genotype frequency of rs2303116 in HLH patients compared with healthy controls
(patients 37.5% VS. controls 13.2%, P = 0.009, OR = 3.900, 95% CI 1.537-9.899).
Multivariate logistic regression analysis indicated that being female (OR 0.350,
95% CI 0.143-0.861, P = 0.018) and of an older age (>43y, OR 0.312, 95% CI 0.118
0.822, P = 0.014) were independent protective factors, and the rs2303116
CT/TTgenotype (OR 3.900, 95% CI 1.537-9.899, P = 0.009) was an independent risk
factor for HLH pathogenesis. By comparing the clinical parameters between HLH
patients with CT/TT and CCgenotypes, we found that the patients with CT/TT
genotype had significantly lower levels of fibrinogen, indicating more aggravated
macrophage activation. In silico analysis of splice factor binding to rs2303116
CT/TT genotypes showed significant decrease for SRSF1 but increase for SRSF6,
which suggested abnormal splicing machinery was associated with HLH pathogenesis.
CONCLUSION: Our study demonstrated for the first time that HLH patients had
significantly higher frequencies of the STXBP2 gene polymorphism rs2303116
variant compared with a healthy Chinese Han population, through clinical
comparisons and further predictions we suggested regulation of alternative
splicing by alleles of SNP rs2303116 could be involved in HLH pathogenesis.
PMID- 27513732
TI - Seasonal variations drive short-term dynamics and partitioning of recently
assimilated carbon in the foliage of adult beech and pine.
AB - 13 CO2 pulse-labelling experiments were performed in situ on adult beeches (Fagus
sylvatica) and pines (Pinus pinaster) at different phenological stages to study
seasonal and interspecific short-term dynamics and partitioning of recently
assimilated carbon (C) in leaves. Polar fraction (PF, including soluble sugars,
amino acids and organic acids) and starch were purified from foliage sampled
during a 10-d chase period. C contents, isotopic compositions and 13 C dynamics
parameters were determined in bulk foliage, PF and starch. Decrease in 13 C
amount in bulk foliage followed a two-pool exponential model highlighting 13 C
partitioning between 'mobile' and 'stable' pools, the relative proportion of the
latter being maximal in beech leaves in May. Early in the growing season, new
foliage acted as a strong C sink in both species, but although young leaves and
needles were already photosynthesizing, the latter were still supplied with
previous-year needle photosynthates 2 months after budburst. Mean 13 C residence
times (MRT) were minimal in summer, indicating fast photosynthate export to
supply perennial organ growth in both species. In late summer, MRT differed
between senescing beech leaves and overwintering pine needles. Seasonal
variations of 13 C partitioning and dynamics in field-grown tree foliage are
closely linked to phenological differences between deciduous and evergreen trees.
PMID- 27513733
TI - Isometric Contractions Are More Analgesic Than Isotonic Contractions for Patellar
Tendon Pain: An In-Season Randomized Clinical Trial.
AB - OBJECTIVE: This study aimed to compare the immediate analgesic effects of 2
resistance programs in in-season athletes with patellar tendinopathy (PT).
Resistance training is noninvasive, a principle stimulus for corticospinal and
neuromuscular adaptation, and may be analgesic. DESIGN: Within-season randomized
clinical trial. Data analysis was conducted blinded to group. SETTING: Subelite
volleyball and basketball competitions. PARTICIPANTS: Twenty jumping athletes
aged more than 16 years, participating in games/trainings 3 times per week with
clinically diagnosed PT. INTERVENTIONS: Two quadriceps resistance protocols were
compared; (1) isometric leg extension holds at 60 degrees knee flexion (80% of
their maximal voluntary isometric contraction) or (2) isotonic leg extension (at
80% of their 8 repetition maximum) 4 times per week for 4 weeks. Time under load
and rest between sets was matched between groups. MAIN OUTCOME MEASURES: (1) Pain
(0-10 numerical rating score) during single leg decline squat (SLDS), measured
preintervention and postintervention sessions. (2) VISA-P, a questionnaire about
tendon pain and function, completed at baseline and after 4 weeks. RESULTS:
Twenty athletes with PT (18 men, mean 22.5 +/- 4.7 years) participated (isotonic
n = 10, isometric n = 10). Baseline median SLDS pain was 5/10 for both groups
(isotonic range 1-8, isometric range 2-8). Isometric contractions produced
significantly greater immediate analgesia (P < 0.002). Week one analgesic
response positively correlated with improvements in VISA-P at 4 weeks (r = 0.64).
CONCLUSIONS: Both protocols appear efficacious for in-season athletes to reduce
pain, however, isometric contractions demonstrated significantly greater
immediate analgesia throughout the 4-week trial. Greater analgesia may increase
the ability to load or perform.
PMID- 27513734
TI - 1,25-Dihydroxyvitamin D Modulates Antibacterial and Inflammatory Response in
Human Cigarette Smoke-Exposed Macrophages.
AB - Cigarette smoking is associated with increased inflammation and defective
antibacterial responses in the airways. Interestingly, vitamin D has been shown
to suppress inflammation and to improve antibacterial defense. However, it is
currently unknown whether vitamin D may modulate inflammation and antibacterial
defects in human cigarette smoke (CS)-exposed airways. To explore these
unresolved issues, alveolar macrophages obtained from non-smoking and smoking
subjects as well as human cigarette smoke extract (CSE)-treated THP-1 macrophages
were stimulated with 1,25-dihydroxyvitamin D (1,25(OH)2D) to address inflammatory
and antibacterial responses. Although basal levels of inflammatory cytokines and
chemokines did not differ between non-smoking and smoking subjects, 1,25(OH)2D
did reduce levels of IL-6, TNF-alpha and MCP-1 in alveolar macrophages in
response to LPS/IFN-gamma, although not statistically significant for TNF-alpha
and IL-6 in smokers. CSE did not significantly alter vitamin D metabolism
(expression levels of CYP24A1 or CYP27B1) in THP-1 macrophages. Furthermore,
stimulation with 1,25(OH)2D reduced mRNA expression levels and/or protein levels
of IL-8, TNF-alpha and MCP-1 in CSE-treated THP-1 macrophages. 1,25(OH)2D did not
improve defects in phagocytosis of E. coli bacteria or the oxidative burst
response in CSE-treated THP-1 macrophages or alveolar macrophages from smokers.
However, 1,25(OH)2D significantly enhanced mRNA expression and/or protein levels
of the antimicrobial peptide cathelicidin in alveolar macrophages and THP-1
macrophages, independently of CS exposure. In conclusion, our results provide the
first evidence that vitamin D could be a new strategy for attenuating airway
inflammation and improving antibacterial defense in CS-exposed airways.
PMID- 27513735
TI - Effects of water scarcity and chemical pollution in aquatic ecosystems: State of
the art.
AB - Water scarcity is an expanding climate and human related condition, which drives
and interacts with other stressors in freshwater ecosystems such as chemical
pollution. In this study we provide an overview of the existing knowledge
regarding the chemical fate, biological dynamics and the ecological risks of
chemicals under water scarcity conditions. We evaluated a total of 15 studies
dealing with the combined effects of chemicals and water scarcity under
laboratory conditions and in the field. The results of these studies have been
elaborated in order to evaluate additive, synergistic or antagonistic responses
of the studied endpoints. As a general rule, it can be concluded that, in
situations of water scarcity, the impacts of extreme water fluctuations are much
more relevant than those of an additional chemical stressor. Nevertheless, the
presence of chemical pollution may result in exacerbated ecological risks in some
particular cases. We conclude that further investigations on this topic would
take advantage on the focus on some specific issues. Experimental (laboratory and
model ecosystem) studies should be performed on different biota groups and life
stages (diapausing eggs, immature stages), with particular attention to those
including traits relevant for the adaptation to water scarcity. More knowledge on
species adaptations and recovery capacity is essential to predict community
responses to multiple stressors and to assess the community vulnerability. Field
studies should be performed at different scales, particularly in lotic systems,
in order to integrate different functional dynamics of the river ecosystem.
Combining field monitoring and experimental studies would be the best option to
reach more conclusive, causal relationships on the effects of co-occurring
stressors. Contribution of these studies to develop ecological models and
scenarios is also suggested as an improvement for the prospective aquatic risk
assessment of chemicals in (semi-)arid areas.
PMID- 27513736
TI - Self-Enhanced Ultrasensitive Photoelectrochemical Biosensor Based on Nanocapsule
Packaging Both Donor-Acceptor-Type Photoactive Material and Its Sensitizer.
AB - In this work, a self-enhanced ultrasensitive photoelectrochemical (PEC) biosensor
was established based on a functionalized nanocapsule packaging both donor
acceptor-type photoactive material and its sensitizer. The functionalized
nanocapsule with self-enhanced PEC responses was achieved first by packaging both
the donor-acceptor-type photoactive material (poly{4,8-bis[5-(2
ethylhexyl)thiophen-2-yl]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl-alt-3-fluoro-2
[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophene-4,6-diyl}, PTB7-Th) and its
sensitizer (nano-C60, fullerene) in poly(ethylene glycol) (PEG) to form a
nanocapsule, which significantly enhanced PEC signal and stability of the PEC
biosensor. Moreover, a quadratic enzymes-assisted target recycling amplification
strategy was introduced to the system for ultrasensitive determination. Compared
with other established PEC biosensors, our proposed self-enhanced approach showed
higher effectivity, accuracy, sensitivity, and convenience without any addition
of coreactant or sensitizers into the testing electrolyte for photocurrent
amplification and performed excellent analytical properties for microRNA
estimation down to femtomole level with microRNA-141 as a model. Additionally,
the proposed PEC biosensor was employed for estimation of microRNA in different
cancer cells and pharmacodynamic evaluation in cancer cells. This self-enhanced
PEC strategy has laid the foundation for fabrication of simple, effective, and
ultrasensitive PEC diagnostic devices, leading to the possibility for early
diagnosis, timely stage estimation, and accurate prognosis judgment of disease.
PMID- 27513737
TI - Simulation of a Real-Time Brain Computer Interface for Detecting a Self-Paced
Hitting Task.
AB - OBJECTIVES: An invasive brain-computer interface (BCI) is a promising
neurorehabilitation device for severely disabled patients. Although some systems
have been shown to work well in restricted laboratory settings, their utility
must be tested in less controlled, real-time environments. Our objective was to
investigate whether a specific motor task could be reliably detected from
multiunit intracortical signals from freely moving animals in a simulated, real
time setting. MATERIALS AND METHODS: Intracortical signals were first obtained
from electrodes placed in the primary motor cortex of four rats that were trained
to hit a retractable paddle (defined as a "Hit"). In the simulated real-time
setting, the signal-to-noise-ratio was first increased by wavelet denoising.
Action potentials were detected, and features were extracted (spike count, mean
absolute values, entropy, and combination of these features) within pre-defined
time windows (200 ms, 300 ms, and 400 ms) to classify the occurrence of a "Hit."
RESULTS: We found higher detection accuracy of a "Hit" (73.1%, 73.4%, and 67.9%
for the three window sizes, respectively) when the decision was made based on a
combination of features rather than on a single feature. However, the duration of
the window length was not statistically significant (p = 0.5). CONCLUSION: Our
results showed the feasibility of detecting a motor task in real time in a less
restricted environment compared to environments commonly applied within invasive
BCI research, and they showed the feasibility of using information extracted from
multiunit recordings, thereby avoiding the time-consuming and complex task of
extracting and sorting single units.
PMID- 27513738
TI - A multi-resolution investigation for postural transition detection and
quantification using a single wearable.
AB - BACKGROUND: Multi-resolution analyses involving wavelets are commonly applied to
data derived from accelerometer-based wearable technologies (wearables) to
identify and quantify postural transitions (PTs). Previous studies fail to
provide rationale to inform their choice of wavelet and scale approximation when
utilising discrete wavelet transforms. This study examines varying combinations
of those parameters to identify best practice recommendations for detecting and
quantifying sit-to-stand (SiSt) and stand-to-sit (StSi) PTs. METHODS: 39 young
and 37 older participants completed three SiSt and StSi PTs on supported and
unsupported chair types while wearing a single tri-axial accelerometer-based
wearable on the lower back. Transition detection and duration were calculated
through peak detection within the signal vector magnitude for a range of wavelets
and scale approximations. A laboratory reference measure (2D video) was used for
comparative analysis. RESULTS: Detection accuracy of wavelet and scale
combinations for the transitions was excellent for both SiSt (87-97%) and StSi
(82-86%) PT-types. The duration of PTs derived from the wearable showed
considerable bias and poor agreement compared with the reference videos. No
differences were observed between chair types and age groups respectively.
CONCLUSIONS: Improved detection of PTs could be achieved through the
incorporation of different wavelet and scale combinations for the assessment of
specific PT types in clinical and free-living settings. An upper threshold of 5th
scale approximations is advocated for improved detection of multiple PT-types.
However, care should be taken estimating the duration of PTs using wearables.
PMID- 27513739
TI - Gait six month and one-year after computer assisted Femur First THR vs.
conventional THR. Results of a patient- and observer- blinded randomized
controlled trial.
AB - A prospective randomized controlled trial is presented that is used to compare
gait performance between the computer assisted Femur First (CAS FF) operation
method and conventional THR (CON). 60 patients underwent a 3D gait analysis of
the lower extremity at pre-operative, 6 months post-operative and twelve months
post-operative. Detailed verification experiments were facilitated to ensure the
quality of data as well as to avoid over-interpreting of the data. The results
confirm a similar data-quality as reported in the literature. Walking speed,
range of motion and symmetry thereof improved over the follow-up period, without
significant differences between the groups. While all parameters do significantly
increase over the follow-up period for both groups, there were no significant
differences between them at any given time-point. Patients undergoing CAS FF
showed a trend to improved hip flexion angle indicating a possible long-term
benefit.
PMID- 27513740
TI - The rotational profile: A study of lower limb axial torsion, hip rotation, and
the foot progression angle in healthy adults.
AB - The purpose of this study was to compare the rotational profile of adults with
higher versus lower foot progression angles (FPA). Tibial torsion, femoral
torsion, hip internal and external rotation and FPA data were collected on one
hundred two healthy volunteers. Data were stratified into Low, Mid, and High FPA
groups to study relationships among the components of the rotational profile and
if there were group differences in the magnitude of torsion angles. Direction of
torsion was also studied as an attempt to look at the incidence of offsetting
between the tibia and femur. Tibial torsion was significantly higher in the High
FPA group (p<0.001) and was significantly related to the FPA (p<=0.01). Femoral
torsion was related to hip internal rotation (p<0.05). Offsetting tibial and
femoral torsions occurred in 59% of subjects with low FPA and 56% of subjects
with high FPA. All subjects in the low FPA group with offsetting had tibial
torsion that followed the FPA and the femurs that were directed opposite. In the
High FPA group, 68% of subjects with offsetting had tibias that followed the FPA.
Stratifying the data by FPA revealed there were significant differences in tibial
torsion among the groups and provided evidence that tibial torsion influences the
direction and magnitude of the FPA. Offsetting torsions between the tibia and
femur were more common in people with higher and lower FPA and had clearer
patterns where the tibia tended to follow the direction of the FPA.
PMID- 27513741
TI - Anxiety is associated with freezing of gait and attentional set-shifting in
Parkinson's disease: A new perspective for early intervention.
AB - Previous research has shown that anxiety in Parkinson's disease (PD) is
associated with freezing of gait (FOG), and may even contribute to the underlying
mechanism. However, limited research has investigated whether PD patients with
FOG (PD+FOG) have higher anxiety levels when compared directly to non-freezing PD
patients (PD-NF) and moreover, how anxiety might contribute to FOG. The current
study evaluated whether: (i) PD+FOG have greater anxiety compared to PD-NF, and
(ii) anxiety in PD is related to attentional set-shifting, in order to better
understand how anxiety might be contributing to FOG. In addition, we explored
whether anxiety levels differed between those PD patients with mild FOG
(PD+MildFOG) compared to PD-NF. Four hundred and sixty-one patients with PD (231
PD-NF, 180 PD+FOG, 50 PD+MildFOG) were assessed using the Freezing of Gait
Questionnaire item 3 (FOG-Q3), Hospital Anxiety and Depression Scale (HADS),
Digit Span Test, Logical Memory Retention Test and Trail Making Tests. Compared
to PD-NF, PD+FOG had significantly greater anxiety (p<0.001). PD+MildFOG,
however, demonstrated similar levels of anxiety as the PD+FOG. In all patients,
the severity of anxiety symptoms was significantly correlated to their degree of
self-reported FOG on FOG-Q3 (p<0.001) and TMT B-A (p=0.039). Similar results were
found for depression. In conclusion, these results confirm the key role played by
anxiety in FOG and also suggest that anxiety might be a promising biomarker for
FOG. Future research should consider whether treating anxiety with
pharmacological and/or cognitive behavioural therapies at early stages of gait
impairment in PD may alleviate troublesome FOG.
PMID- 27513742
TI - Xenopsylla brasiliensis Fleas in Plague Focus Areas, Madagascar.
PMID- 27513743
TI - Chronic Inhibition of STAT3/STAT5 in Treatment-Resistant Human Breast Cancer Cell
Subtypes: Convergence on the ROS/SUMO Pathway and Its Effects on xCT Expression
and System xc- Activity.
AB - Pharmacologically targeting activated STAT3 and/or STAT5 has been an active area
of cancer research. The cystine/glutamate antiporter, system xc-, contributes to
redox balance and export of intracellularly produced glutamate in response to up
regulated glutaminolysis in cancer cells. We have previously shown that blocking
STAT3/5 using the small molecule inhibitor, SH-4-54, which targets the SH2
domains of both proteins, increases xCT expression, thereby increasing system xc-
activity in human breast cancer cells. The current investigation demonstrates
that chronic SH-4-54 administration, followed by clonal selection of treatment
resistant MDA-MB-231 and T47D breast cancer cells, elicits distinct subtype
dependent effects. xCT mRNA and protein levels, glutamate release, and cystine
uptake are decreased relative to untreated passage-matched controls in triple
negative MDA-MB-231 cells, with the inverse occurring in estrogen-responsive T47D
cells. This "ying-yang" effect is linked with a shifted balance between the
phosphorylation status of STAT3 and STAT5, intracellular ROS levels, and STAT5
SUMOylation/de-SUMOylation. STAT5 emerged as a definitive negative regulator of
xCT at the transcriptional level, while STAT3 activation is coupled with
increased system xc- activity. We propose that careful classification of a
patient's breast cancer subtype is central to effectively targeting STAT3/5 as a
therapeutic means of treating breast cancer, particularly given that xCT is
emerging as an important biomarker of aggressive cancers.
PMID- 27513744
TI - Assessing Finger Joint Biomechanics by Applying Equal Force to Flexor Tendons In
Vitro Using a Novel Simultaneous Approach.
AB - BACKGROUND: The flexor digitorum superficialis (FDS) and flexor digitorum
profundus (FDP) are critical for finger flexion. Although research has recently
focused on these tendons' coactivity, their contributions in different tasks
remain unclear. This study created a novel simultaneous approach to investigate
the coactivity between the tendons and to clarify their contributions in
different tasks. METHODS: Ten human cadaveric hands were mounted on our custom
frame with the FDS and FDP of the third finger looped through a mechanical pulley
connected to a force transducer. Joint range of motion, tendon excursion and
loading force were recorded during individual joint motion and free joint
movement from rest to maximal flexion. Each flexor tendon's moment arm was then
calculated. RESULTS: In individual motions, we found that the FDP contributed
more than the FDS in proximal interphalangeal (PIP) joint motion, with an overall
slope of 1.34 and all FDP-to-FDS excursion (P/S) ratios greater than 1.0 with
force increase. However, the FDP contributed less than the FDS in
metacarpophalangeal (MCP) joint motion, with an overall slope of 0.95 and P/S
ratios smaller than 1.0 throughout the whole motion except between 1.9% and 13.1%
force. In free joint movement, the FDP played a greater role than the FDS, with
an overall ratio of 1.37 and all P/S ratios greater than 1.0. CONCLUSIONS: The
new findings include differences in finger performance and excursion amounts
between the FDS and FDP throughout flexion. Such findings may provide the basis
for new hand models and treatments.
PMID- 27513745
TI - Correction: Hydrophobic Core Variations Provide a Structural Framework for
Tyrosine Kinase Evolution and Functional Specialization.
AB - [This corrects the article DOI: 10.1371/journal.pgen.1005885.].
PMID- 27513746
TI - Microstructural Correlates of Emotional Attribution Impairment in Non-Demented
Patients with Amyotrophic Lateral Sclerosis.
AB - Impairments in the ability to recognize and attribute emotional states to others
have been described in amyotrophic lateral sclerosis patients and linked to the
dysfunction of key nodes of the emotional empathy network. Microstructural
correlates of such disorders are still unexplored. We investigated the white
matter substrates of emotional attribution deficits in a sample of amyotrophic
lateral sclerosis patients without cognitive decline. Thirteen individuals with
either probable or definite amyotrophic lateral sclerosis and 14 healthy controls
were enrolled in a Diffusion Tensor Imaging study and administered the Story
based Empathy Task, assessing the ability to attribute mental states to others
(i.e., Intention and Emotion attribution conditions). As already reported, a
significant global reduction of empathic skills, mainly driven by a failure in
Emotion Attribution condition, was found in amyotrophic lateral sclerosis
patients compared to healthy subjects. The severity of this deficit was
significantly correlated with fractional anisotropy along the forceps minor, genu
of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The
involvement of frontal commissural fiber tracts and right ventral associative
fronto-limbic pathways is the microstructural hallmark of the impairment of high
order processing of socio-emotional stimuli in amyotrophic lateral sclerosis.
These results support the notion of the neurofunctional and neuroanatomical
continuum between amyotrophic lateral sclerosis and frontotemporal dementia.
PMID- 27513747
TI - Antiglycation and Antioxidant Properties of Momordica charantia.
AB - The accumulation of advanced glycation endproducts (AGEs) and oxidative stress
underlie the pathogenesis of diabetic complications. In many developing
countries, diabetes treatment is unaffordable, and plants such as bitter gourd
(or bitter melon; Momordica charantia) are used as traditional remedies because
they exhibit hypoglycaemic properties. This study compared the antiglycation and
antioxidant properties of aqueous extracts of M. charantia pulp (MCP), flesh
(MCF) and charantin in vitro. Lysozyme was mixed with methylglyoxal and 0-15
mg/ml of M. charantia extracts in a pH 7.4 buffer and incubated at 37 degrees C
for 3 days. Crosslinked AGEs were assessed using gel electrophoresis, and the
carboxymethyllysine (CML) content was analyzed by enzyme-linked immunosorbent
assays. The antioxidant activities of the extracts were evaluated using assays to
assess DPPH (1,1-diphenyl-2-picryl-hydrazyl) and hydroxyl radical scavenging
activities, metal-chelating activity and reducing power of the extracts. The
phenolic, flavonol and flavonoid content of the extracts were also determined.
All extracts inhibited the formation of crosslinked AGEs and CML in a dose
dependent manner, with MCF being the most potent. The antioxidant activity of MCF
was higher than that of MCP, but MCP showed the highest metal-chelating activity.
MCF had the highest phenolic and flavonoid contents, whereas MCP had the highest
flavonol content. M. charantia has hypoglycaemic effects, but this study shows
that M. charantia extracts are also capable of preventing AGE formation in vitro.
This activity may be due to the antioxidant properties, particularly the total
phenolic content of the extracts. Thus, the use of M. charantia deserves more
attention, as it may not only reduce hyperglycaemia but also protect against the
build-up of tissue AGEs and reduce oxidative stress in patients with diabetes.
PMID- 27513748
TI - The Integration of Epistasis Network and Functional Interactions in a GWAS
Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.
AB - Although many diseases and traits show large heritability, few genetic variants
have been found to strongly separate phenotype groups by genotype. Complex
regulatory networks of variants and expression of multiple genes lead to small
individual-variant effects and difficulty replicating the effect of any single
variant in an affected pathway. Interaction network modeling of GWAS identifies
effects ignored by univariate models, but population differences may still cause
specific genes to not replicate. Integrative network models may help detect
indirect effects of variants in the underlying biological pathway. In this study,
we used gene-level functional interaction information from the Integrative Multi
species Prediction (IMP) tool to reveal important genes associated with a complex
phenotype through evidence from epistasis networks and pathway enrichment. We
test this method for augmenting variant-based network analyses with functional
interactions by applying it to a smallpox vaccine immune response GWAS. The
integrative analysis spotlights the role of genes related to retinoid X receptor
alpha (RXRA), which has been implicated in a previous epistasis network analysis
of smallpox vaccine.
PMID- 27513749
TI - Comparison of Statistical Algorithms for the Detection of Infectious Disease
Outbreaks in Large Multiple Surveillance Systems.
AB - A large-scale multiple surveillance system for infectious disease outbreaks has
been in operation in England and Wales since the early 1990s. Changes to the
statistical algorithm at the heart of the system were proposed and the purpose of
this paper is to compare two new algorithms with the original algorithm. Test
data to evaluate performance are created from weekly counts of the number of
cases of each of more than 2000 diseases over a twenty-year period. The time
series of each disease is separated into one series giving the baseline
(background) disease incidence and a second series giving disease outbreaks. One
series is shifted forward by twelve months and the two are then recombined,
giving a realistic series in which it is known where outbreaks have been added.
The metrics used to evaluate performance include a scoring rule that
appropriately balances sensitivity against specificity and is sensitive to
variation in probabilities near 1. In the context of disease surveillance, a
scoring rule can be adapted to reflect the size of outbreaks and this was done.
Results indicate that the two new algorithms are comparable to each other and
better than the algorithm they were designed to replace.
PMID- 27513750
TI - Cadmium Exposure Enhances Bisphenol A-Induced Genotoxicity through 8-Oxoguanine
DNA Glycosylase-1 OGG1 Inhibition in NIH3T3 Fibroblast Cells.
AB - BACKGROUND: Both cadmium (Cd) and bisphenol A (BPA) are commonly encountered in
humans' daily activities, but their combined genotoxic effects remain unclear.
METHODS: In the present study, we exposed a mouse embryonic fibroblast cell line
(NIH3T3) to Cd for 24 h, followed by a 24 h BPA exposure to evaluate toxicity.
The cytotoxicity was evaluated by viability with CCK-8 assay and lactate
dehydrogenase (LDH) release. Reactive oxygen species (ROS) production was
measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA). And DNA damage was
measured by 8-hydroxydeoxyguanosine (8-OHdG), phosphorylated H2AX (gammaH2AX) and
the comet assay. The flow cytometry was used to detect cell cycle distribution,
and apoptosis was determined by TUNEL assay and western blot against poly-ADP
ribose polymerase (PARP). RESULTS: The results showed that Cd or BPA treatments
alone (with the exception of BPA exposure at 50 MUM) did not alter cell
viability. However, pre-treatment with Cd aggravated the BPA-induced reduction in
cell viability; increased BPA-induced LDH release, ROS production, DNA damage and
G2 phase arrest; and elevated BPA-induced TUNEL-positive cells and the expression
levels of cleaved PARP. Cd exposure concurrently decreased the expression of 8
oxoguanine-DNA glycosylase-1 (OGG1), whereas OGG1 over-expression abolished the
enhancement of Cd on BPA-induced genotoxicity and cytotoxicity. CONCLUSION: These
findings indicate that Cd exposure aggravates BPA-induced genotoxicity and
cytotoxicity through OGG1 inhibition.
PMID- 27513751
TI - Genetic Structure of Modern Durum Wheat Cultivars and Mediterranean Landraces
Matches with Their Agronomic Performance.
AB - A collection of 172 durum wheat landraces from 21 Mediterranean countries and 20
modern cultivars were phenotyped in 6 environments for 14 traits including
phenology, biomass, yield and yield components. The genetic structure of the
collection was ascertained with 44 simple sequence repeat markers that identified
448 alleles, 226 of them with a frequency lower than 5%, and 10 alleles per locus
on average. In the modern cultivars all the alleles were fixed in 59% of the
markers. Total genetic diversity was HT = 0.7080 and the genetic differentiation
value was GST = 0.1730. STRUCTURE software allocated 90.1% of the accessions in
five subpopulations, one including all modern cultivars, and the four containing
landrace related to their geographic origin: eastern Mediterranean, eastern
Balkans and Turkey, western Balkans and Egypt, and western Mediterranean. Mean
yield of subpopulations ranged from 2.6 t ha-1 for the western Balkan and
Egyptian landraces to 4.0 t ha-1 for modern cultivars, with the remaining three
subpopulations showing similar values of 3.1 t ha-1. Modern cultivars had the
highest number of grains m-2 and harvest index, and the shortest cycle length.
The diversity was lowest in modern cultivars (HT = 0.4835) and highest in
landraces from the western Balkans and Egypt (HT = 0.6979). Genetic diversity and
AMOVA indicated that variability between subpopulations was much lower (17%) than
variability within them (83%), though all subpopulations had similar biomass
values in all growth stages. A dendrogram based on simple sequence repeat data
matched with the clusters obtained by STRUCTURE, improving this classification
for some accessions that have a large admixture. landraces included in the
subpopulation from the eastern Balkans and Turkey were separated into two
branches in the dendrogram drawn with phenotypic data, suggesting a different
origin for the landraces collected in Serbia and Macedonia. The current study
shows a reliable relationship between genetic and phenotypic population
structures, and the connection of both with the geographic origin of the
landraces.
PMID- 27513752
TI - Spheno-Occipital Synchondrosis Fusion Correlates with Cervical Vertebrae
Maturation.
AB - The aim of this study was to determine the relationship between the closure stage
of the spheno-occipital synchondrosis and the maturational stage of the cervical
vertebrae (CVM) in growing and young adult subjects using cone beam computed
tomography (CBCT). CBCT images with an extended field of view obtained from 315
participants (148 females and 167 males; mean age 15.6 +/-7.3 years; range 6 to
23 years) were analyzed. The fusion status of the synchondrosis was determined
using a five-stage scoring system; the vertebral maturational status was
evaluated using a six-stage stratification (CVM method). Ordinal regression was
used to study the ability of the synchondrosis stage to predict the vertebral
maturation stage. Vertebrae and synchondrosis had a strong significant
correlation (r = 0.89) that essential was similar for females (r = 0.88) and
males (r = 0.89). CVM stage could be accurately predicted from synchondrosis
stage by ordinal regression models. Prediction equations of the vertebral stage
using synchondrosis stage, sex and biological age as predictors were developed.
Thus this investigation demonstrated that the stage of spheno-occipital
synchondrosis, as determined in CBCT images, is a reasonable indicator of growth
maturation.
PMID- 27513753
TI - Basal Complex and Basal Venation of Odonata Wings: Structural Diversity and
Potential Role in the Wing Deformation.
AB - Dragonflies and damselflies, belonging to the order Odonata, are known to be
excellent fliers with versatile flight capabilities. The ability to fly over a
wide range of speeds, high manoeuvrability and great agility are a few
characteristics of their flight. The architecture of the wings and their
structural elements have been found to play a major role in this regard. However,
the precise influence of individual wing components on the flight performance of
these insects remains unknown. The design of the wing basis (so called basal
complex) and the venation of this part are responsible for particular
deformability and specific shape of the wing blade. However, the wing bases are
rather different in representatives of different odonate groups. This presumably
reflects the dimensions of the wings on one hand, and different flight
characteristics on the other hand. In this article, we develop the first three
dimensional (3D) finite element (FE) models of the proximal part of the wings of
typical representatives of five dragonflies and damselflies families. Using a
combination of the basic material properties of insect cuticle, a linear elastic
material model and a nonlinear geometric analysis, we simulate the mechanical
behaviour of the wing bases. The results reveal that although both the basal
venation and the basal complex influence the structural stiffness of the wings,
it is only the latter which significantly affects their deformation patterns. The
use of numerical simulations enabled us to address the role of various wing
components such as the arculus, discoidal cell and triangle on the camber
formation in flight. Our study further provides a detailed representation of the
stress concentration in the models. The numerical analysis presented in this
study is not only of importance for understanding structure-function relationship
of insect wings, but also might help to improve the design of the wings for
biomimetic micro-air vehicles (MAVs).
PMID- 27513754
TI - Potential Impacts of Offshore Wind Farms on North Sea Stratification.
AB - Advances in offshore wind farm (OWF) technology have recently led to their
construction in coastal waters that are deep enough to be seasonally stratified.
As tidal currents move past the OWF foundation structures they generate a
turbulent wake that will contribute to a mixing of the stratified water column.
In this study we show that the mixing generated in this way may have a
significant impact on the large-scale stratification of the German Bight region
of the North Sea. This region is chosen as the focus of this study since the
planning of OWFs is particularly widespread. Using a combination of idealised
modelling and in situ measurements, we provide order-of-magnitude estimates of
two important time scales that are key to understanding the impacts of OWFs: (i)
a mixing time scale, describing how long a complete mixing of the stratification
takes, and (ii) an advective time scale, quantifying for how long a water parcel
is expected to undergo enhanced wind farm mixing. The results are especially
sensitive to both the drag coefficient and type of foundation structure, as well
as the evolution of the pycnocline under enhanced mixing conditions-both of which
are not well known. With these limitations in mind, the results show that OWFs
could impact the large-scale stratification, but only when they occupy extensive
shelf regions. They are expected to have very little impact on large-scale
stratification at the current capacity in the North Sea, but the impact could be
significant in future large-scale development scenarios.
PMID- 27513755
TI - Selection of Suitable Reference Genes for RT-qPCR Normalization under Abiotic
Stresses and Hormone Stimulation in Persimmon (Diospyros kaki Thunb).
AB - The success of quantitative real-time reverse transcription polymerase chain
reaction (RT-qPCR) to quantify gene expression depends on the stability of the
reference genes used for data normalization. To date, systematic screening for
reference genes in persimmon (Diospyros kaki Thunb) has never been reported. In
this study, 13 candidate reference genes were cloned from 'Nantongxiaofangshi'
using information available in the transcriptome database. Their expression
stability was assessed by geNorm and NormFinder algorithms under abiotic stress
and hormone stimulation. Our results showed that the most suitable reference
genes across all samples were UBC and GAPDH, and not the commonly used persimmon
reference gene ACT. In addition, UBC combined with RPII or TUA were found to be
appropriate for the "abiotic stress" group and alpha-TUB combined with PP2A were
found to be appropriate for the "hormone stimuli" group. For further validation,
the transcript level of the DkDREB2C homologue under heat stress was studied with
the selected genes (CYP, GAPDH, TUA, UBC, alpha-TUB, and EF1-alpha). The results
suggested that it is necessary to choose appropriate reference genes according to
the test materials or experimental conditions. Our study will be useful for
future studies on gene expression in persimmon.
PMID- 27513756
TI - Ingenol Mebutate 500 ug on the Cheekbones with Concomitant Conjunctivitis.
AB - Ingenol mebutate induces strong inflammation after a single application already.
This must be taken into account when prescribing the drug, as mistakes in the
application may results in severe side effects. Here, we report the case of a 72
year-old woman who applied ingenol mebutate on the cheekbones and developed a
pronounced conjunctivitis, needing topical corticosteroids. The treatment was
intended for the actinic keratosis she had on the chest, and the regimen of 2
consecutive once daily applications of ingenol mebutate at 500 ug/g had been
prescribed as registered. The inadvertent application on the thin skin of the
cheekbones led to a pronounced inflammation. With topical steroids followed by
fusidic acid, both conjunctivitis and skin inflammation resolved within a few
days. The skin showed erythema for a few weeks, but after 3 months, the patient
presented a perfectly smooth skin and was very happy with the cosmetic outcome.
This suggests that the cheekbones are a sensitive site for ingenol mebutate, but
that intense inflammation should not scare physician or patient, as clinical
remission with excellent healing can still be expected.
PMID- 27513757
TI - Internet-Based Cognitive Behavioral Therapy for Social Anxiety with and without
Guidance Compared to a Wait List in China: A Propensity Score Study.
PMID- 27513759
TI - Erratum.
PMID- 27513758
TI - D-Dimer Levels Predict Myocardial Injury in ST-Segment Elevation Myocardial
Infarction: A Cardiac Magnetic Resonance Imaging Study.
AB - OBJECTIVES: Elevated D-dimer levels on admission predict prognosis in patients
undergoing primary percutaneous coronary intervention (PCI) for ST-segment
elevation myocardial infarction (STEMI), but the association of D-dimer levels
with structural markers of myocardial injury in these patients is unknown.
METHODS: We performed cardiac magnetic resonance (CMR) imaging in 208 patients
treated with primary PCI for STEMI. CMR was performed a median of 3 days after
the index procedure. Of the 208 patients studied, 75 patients had D-dimer levels
above the normal range on admission (>0.5 MUg/mL; high D-dimer group) while 133
had normal levels (<=0.5 MUg/mL; low D-dimer group). The primary outcome was
myocardial infarct size assessed by CMR. Secondary outcomes included area at risk
(AAR), microvascular obstruction (MVO) area, and myocardial salvage index (MSI).
RESULTS: In CMR analysis, myocardial infarct size was larger in the high D-dimer
group than in the low D-dimer group (22.3% [16.2-30.5] versus 18.8% [10.7-26.7];
p = 0.02). Compared to the low D-dimer group, the high D-dimer group also had a
larger AAR (38.1% [31.7-46.9] versus 35.8% [24.2-45.3]; p = 0.04) and a smaller
MSI (37.7 [28.2-46.9] versus 47.1 [33.2-57.0]; p = 0.01). In multivariate
analysis, high D-dimer levels were significantly associated with larger
myocardial infarct (OR 2.59; 95% CI 1.37-4.87; p<0.01) and lower MSI (OR 2.62;
95% CI 1.44-4.78; p<0.01). CONCLUSIONS: In STEMI patients undergoing primary PCI,
high D-dimer levels on admission were associated with a larger myocardial infarct
size, a greater extent of AAR, and lower MSI, as assessed by CMR data. Elevated
initial D-dimer level may be a marker of advanced myocardial injury in patients
treated with primary PCI for STEMI.
PMID- 27513760
TI - A gammaA-Crystallin Mouse Mutant Secc with Small Eye, Cataract and Closed Eyelid.
AB - Cataract is the most common cause of visual loss in humans. A spontaneously
occurred, autosomal dominant mouse mutant Secc, which displayed combined features
of small eye, cataract and closed eyelid was discovered in our laboratory. In
this study, we identified the mutation and characterized the cataract phenotype
of this novel Secc mutant. The Secc mutant mice have eyelids that remain half
closed throughout their life. The mutant lens has a significant reduction in size
and with opaque spots clustered in the centre. Histological analysis showed that
in the core region of the mutant lens, the fiber cells were disorganized and
clefts and vacuoles were observed. The cataract phenotype was evident from new
born stage. We identified the Secc mutation by linkage analysis using whole
genome microsatellite markers and SNP markers. The Secc locus was mapped at
chromosome 1 flanked by SNPs rs3158129 and rs13475900. Based on the chromosomal
position, the candidate cataract locus gamma-crystallin gene cluster (Cryg) was
investigated by sequencing. A single base deletion (299delG) in exon 3 of Cryga
which led to a frame-shift of amino acid sequence from position 91 was
identified. As a result of this mutation, the sequences of the 3rd and 4th Greek
key motifs of the gammaA-crystallin are replaced with an unrelated C-terminal
peptide of 75 residues long. Coincidentally, the point mutation generated a
HindIII restriction site, allowing the identification of the CrygaSecc mutant
allele by RFLP. Western blot analysis of 3-week old lenses showed that the
expression of gamma-crystallins was reduced in the CrygaSecc mutant. Furthermore,
in cell transfection assays using CrygaSecc mutant cDNA expression constructs in
293T, COS-7 and human lens epithelial B3 cell lines, the mutant gammaA
crystallins were enriched in the insoluble fractions and appeared as insoluble
aggregates in the transfected cells. In conclusion, we have demonstrated that the
Secc mutation leads to the generation of CrygaSecc proteins with reduced
solubility and prone to form aggregates within lens cells. Accumulation of mutant
proteins in the lens fibers would lead to cataract formation in the Secc mutant.
PMID- 27513761
TI - The Effect of the Exon-3-Deleted Growth Hormone Receptor on Pegvisomant-Treated
Acromegaly: A Systematic Review and Meta-Analysis.
AB - BACKGROUND: The common exon 3 deletion polymorphism of the growth hormone
receptor (d3-GHR) is associated with disease severity in acromegaly patients. The
GHR antagonist pegvisomant (PEGV) is highly effective in treating severe
acromegaly. Response to PEGV treatment seems to be influenced by d3-GHR and
appears to be more responsive to PEGV, although available results remain
conflicting. OBJECTIVE: To assess the influence of d3-GHR on the responsiveness
of acromegaly patients to PEGV by compiling the evidence derived from the largest
available studies. DESIGN: A systematic review of the literature identified three
published studies and one conference abstract. Acromegaly patients (n = 324,
49.7% d3-GHR carriers) were treated with either PEGV monotherapy or PEGV combined
with long-acting somatostatin analogues and/or cabergoline. A meta-analysis of
raw data from these studies was performed. RESULTS: No significant effect of the
d3-GHR was observed while bringing insulin-like growth factor I (IGF-I) levels
below the upper limit of normal with PEGV, which was defined as the lowest IGF-I
level during PEGV treatment (mean difference: -2.3%; 95% CI: -6.5 to 1.8, p =
0.270). The PEGV dose required to achieve the lowest IGF-I levels was also not
significantly influenced by individuals carrying d3-GHR (mean difference: 4.1 mg
weekly; 95% CI: -5.1 to 13.2, p = 0.385). For both outcomes, separate analysis of
PEGV monotherapy and combination treatment gave similar results. CONCLUSION: Our
findings suggest that the d3-GHR polymorphism has no effect on biochemical
disease control in acromegaly, as it is not of added value for either the
prediction of PEGV responsiveness or the determination of the required PEGV dose.
PMID- 27513762
TI - Spanish version of the Kidney Disease Knowledge Survey (KiKS) in Peru: cross
cultural adaptation and validation.
AB - INTRODUCTION: Chronic kidney disease (CKD) affects 50 million people globally.
Several studies show the importance of implementing interventions that enhance
patients? knowledge about their disease. In 2011 the Kidney Disease Knowledge
Survey (KiKS) was developed: a questionnaire that assesses the specific knowledge
about chronic kidney disease in pre-dialysis patients. OBJECTIVE: To translate to
Spanish, culturally adapt and validate the Kidney Disease Knowledge Survey
questionnaire in a population of patients with pre-dialysis chronic kidney
disease. METHODS: We carried out a Spanish translation and cross-cultural
adaptation of the Kidney Disease Knowledge Survey questionnaire. Subsequently, we
determined its validity and reliability. We determined the validity through
construct validity; and reliability by evaluating its internal consistency and
its intra-observer reliability (test-retest). RESULTS: We found a good internal
consistency (Kuder-Richardson = 0.85). The intra-observer reliability was
measured by the intra-class correlation coefficient that yielded a value of 0.78
(95% CI: 0.5-1.0). This value indicated a good reproducibility; also, the mean
difference of -1.1 test-retest SD 6.0 (p = 0.369) confirms this finding.
CONCLUSION: The translated Spanish version of the Kidney Disease Knowledge Survey
is acceptable and equivalent to the original version; it also has a good
reliability, validity and reproducibility. Therefore, it can be used in a
population of patients with pre-dialysis chronic kidney disease.
PMID- 27513764
TI - Emerging Roles of in Situ Generated Quinone Methides in Metal-Free Catalysis.
AB - ortho-Quinone methides have emerged recently as useful electrophiles in metal
free catalysis. New strategies to access these species in situ that are
compatible with simultaneous nucleophile generation have provided a suite of
innovative and selective transformations accessing heterocycles for use in
organic synthesis.
PMID- 27513763
TI - Dying blood mononuclear cell secretome exerts antimicrobial activity.
AB - BACKGROUND: Several activities are attributed to antimicrobial peptides (AMPs),
including bacterial killing, leucocyte recruitment and angiogenesis. Despite
promises of advanced cellular therapies for treatment of diabetic foot ulcer, it
is currently accepted that paracrine factors rather than cellular components are
causative for the observed effects. Whether AMPs are present in the mononuclear
cell (MNC) secretome (MNC-sec) of white blood cells that are beneficial in
experimental wound healing is not known. MATERIALS AND METHODS: Antimicrobial
activity of the secretomes of nonirradiated (MNC-sec) and gamma-irradiated MNCs
(MNC-sec rad) was analysed by microdilution assay. AMPs were determined by
quantitative real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay
(ELISA). Whether human MNC-sec rad causes AMP secretion in vivo was examined in
an experimental rat model. Image flow cytometry was used to determine the type of
cell death induced in MNCs after exposure to gamma-radiation. RESULTS: The
antimicrobial activity assay revealed a bactericidal activity of MNC-sec rad and
to a lesser degree also of MNC-sec. Image flow cytometry showed that gamma
irradiation of MNCs induced early apoptosis followed mainly by necroptosis. RT
PCR and ELISA revealed a high abundance of different AMPs in the secretome of
MNCs. In addition, human MNC-sec elicited an increase in de novo endogenous AMP
production in rats in vivo. CONCLUSION: We provide evidence that the secretome of
MNCs has direct and indirect positive effects on the immune defence system,
including augmentation of antibacterial properties. Our data further suggest that
necroptosis could play a key role for the release of paracrine factors and the
therapeutic action of MNC-sec rad.
PMID- 27513765
TI - Clinical Considerations for Vascularized Composite Allotransplantation of the
Eye.
AB - Vascularized composite allotransplantation represents a potential shift in
approaches to reconstruction of complex defects resulting from congenital
differences as well as trauma and other acquired pathology. Given the highly
specialized function of the eye and its unique anatomical components,
vascularized composite allotransplantation of the eye is an appealing method for
restoration, replacement, and reconstruction of the nonfunctioning eye. Herein,
we describe conventional treatments for eye restoration and their shortcomings as
well as recent research and events that have brought eye transplantation closer
to a potential clinical reality. In this article, we outline some potential
considerations in patient selection, donor facial tissue procurement, eye tissue
implantation, surgical procedure, and potential for functional outcomes.
PMID- 27513766
TI - Facing The World in Vietnam: Feedback From Trainees on the Educational Value of
Surgical Missions to Help Patients With Craniofacial Deformities.
AB - BACKGROUND: Education and training of local healthcare staff is a crucial
component of a surgical mission. Facing The World (FTW) is a UK-based
craniofacial charity that provides facial reconstructive surgery to children with
complex, craniofacial anomalies. As part of its global initiative, FTW has
developed a training outreach program in Vietnam. The aim of this study was to
analyze feedback data to evaluate the educational value of the training program
and identify areas for improvement. METHODS: Feedback was obtained through both 5
point Likert scale and open-ended response questions on written questionnaires.
Six postmission reports were reviewed, and used as a base for the content of the
questionnaires. Selective sampling was used, with questionnaires distributed to
all Vietnamese and UK trainees who have been part of the FTW training program.
RESULTS: Seven Vietnamese trainee questionnaires were completed, a response rate
of 87.5%. Twelve UK trainees completed the feedback questionnaire, giving a
response rate of 85.7%. One hundred percent of local trainees and 83.3% of UK
trainees found the training program to be useful or very useful, with no trainees
deeming the training program not useful or of no use at all. CONCLUSION: The
training missions offered by FTW have successfully provided education to both UK
and Vietnamese surgeons in Craniofacial surgical techniques and patient care. No
negative responses were identified in both questionnaires. The feedback provides
evidence of FTW's effective training program, while allowing insight into where
further improvements can be made.
PMID- 27513767
TI - Anterior Fontanelle Wormian Bone With Exomphalos Major and Dysmorphic Facial
Features: A Previously Unseen Association?
AB - Wormian bones are independent ossification centers found within cranial sutures
or fontanelles. Though common in adult populations, their presence in children
can be associated with several conditions such as osteogenesis imperfecta,
hypothyroidism, pyknodysostosis, cleidocranial dysostosis, rickets, and
acrocallosal syndrome. These conditions encompass a large range of clinical
features but there has only been 1 other reported patient of exomphalos occurring
concurrently with these ossicles. The authors present the case of a child with an
anterior fontanellar Wormian bone, dysmorphic facial features, and exomphalos
major born to unaffected parents. The pattern of features seen in this child did
not closely match any condition commonly associated with Wormian bones. The only
other reported case of both Wormian bone and exomphalos was in a child with
acrocallosal syndrome who presented with more severe dysmorphic features than
seen here. It is possible that this patient represents a previously unknown
association between acrocallosal syndrome and exomphalos or a less severe variant
of the condition. Conversely, this patient may possibly illustrate a newly
discovered association between Wormian bones, facial dysmorphism, and midline
abdominal defects.
PMID- 27513768
TI - A Cheap Hand-Made Mandibular External Fixator?
AB - The external mandibular fixator is one of the tools that maxillofacial have to
contain complex fractures, in particular in the context of ballistic traumas or
comminuted fractures.The authors present a craft external fixator inspired from
Joe Hall Morris fixation. This technique, particularly cheap, can be an
alternative to a conventional external fixator. The authors report their advices
and tricks to guide the implementation of that external fixator and avoid
pitfalls. Indications of this surgical device are discussed.
PMID- 27513769
TI - Three-Dimensional Printing of Reduction Template in the Contouring of
Craniofacial Fibrous Dysplasia.
AB - BACKGROUND: Contouring is a minimal invasive procedure to remove excess lesions
and restore facial appearance of patients with craniofacial fibrous dysplasia;
however, it is difficult to measure the amount of excess lesions. This study is
to demonstrate the use of reduction template produced by three-dimensional
printer in contouring procedure. METHODS: Computed tomography data were
reconstructed into a three-dimensional model by Mimics software. The unaffected
side was mirrored and superimposed on the affected side. Excess fibrous dysplasia
lesions were calculated by Boolean operations. Lesions to be removed were
separated and saved as stereolithography file. This model was further constructed
in 3-matic package of Mimics software, and several holes were designed to
indicate the variation in depth. Finally, the virtual model was exported into
three-dimensional printer to produce physical template. RESULTS: With the direct
guidance of three-dimensional reduction template, contouring procedure was
performed easily and accurately. Good facial symmetry was achieved with reduced
operative time and loss of bleeding. CONCLUSIONS: The application of reduction
template produced by three-dimensional printer in contouring procedure improves
the efficient and safety of surgery. Good outcomes are obtained without extra
requirement in craniofacial surgery.
PMID- 27513770
TI - Quantifying Craniometric Change Early After Fronto-Orbital Advancement in Metopic
Synostosis.
AB - Frontal orbital advancement (FOA) for metopic synostosis results in cranial vault
expansion, supporting underlying growth of the developing brain and improving
head shape. Previous studies have shown that FOA in younger infants leads to a
greater incidence of long-term growth restriction of intracranial volume;
however, it is still unknown as to whether this is due to undercorrection at the
time of surgery versus primary suture pathology. The purpose of our study is to
provide a method for objective analyses of intracranial volumes in the early post
FOA period. A retrospective chart review was conducted on patients who underwent
FOA over a 10-year period by a single surgeon. Data collected included patient
characteristics and clinical outcomes. Radiological analysis of intracranial
volumes pre- and post-FOA was determined using Amira volume-rendering software.
Average increase in intracranial volume at 6 weeks post-FOA was 139.27 mL (80.01
225.25 mL) with average relative cranial vault expansion of 18.1% (3.3-48%).
Patients who underwent FOA older than 12 months of age had an average increase in
intracranial volume of 8.5% (3.3-13.1%). Patients younger than 12 months had a
statistically higher average increase of 25% (12.8-48%). Frontal orbital
advancement effectively increases intracranial volume in patients with metopic
synostosis. When compared with older patients, patients younger than 1 year of
age have a greater relative increase in intracranial volume in the immediate
postoperative period. Quantifying cranial vault expansion after FOA can assist
surgeons in surgical planning as well as in measuring and monitoring clinical
outcomes within and across craniofacial centers regardless of technique.
PMID- 27513771
TI - Surgical Template to Minimize the Damage of Tooth Buds in Young Children With
Mandibular Distraction Osteogenesis.
AB - BACKGROUND: Mandibular distraction osteogenesis has become one of the most
powerful reconstructive techniques for the treatment of mandibular deformities in
young children. Damage to the tooth buds is often cited as a complication of it.
The purpose of this study was to precisely design the osteotomy line and avoid
the damage of tooth buds at the mandibular angle area with the help of surgical
template. METHODS: Six patients aged from 6 to 10 years were selected in this
study. Three-dimensional computed tomography data was put into Mimics software
for preoperative planning the osteotomy line and the accurate placement of the
distractor based on the exact position of tooth follicle. And then the surgical
template was manufactured by a three-dimensional printer with rapid prototyping
technique. The surgeons were guided to perform the osteotomy aided with the
prefabricated template through an intraoral approach. Distraction began 7 days
postoperation with a rate of 1 mm/d and the distractor was removed after a 6 to 8
months consolidation period. The tooth buds were observed through radiographs
that were performed at 5 time intervals: before distraction, at the end of
latency, at the end of distraction, at the end of consolidation and 2 years of
the postoperation to remove the distractor. RESULTS: The average follow-up time
is 24 months. Facial appearance and occlusal plane of all the young patients were
greatly improved without complications. From the radiological observation, the
tooth buds was intact after the surgery and the second molar normally erupted
after removing the distractor. CONCLUSIONS: The surgical template was considered
to be helpful in improving the surgical accuracy and avoiding the tooth buds
damage during mandibular distraction osteogenesis.
PMID- 27513772
TI - Virtual Assessment of Sex: Linear and Angular Traits of the Mandibular Ramus
Using Three-Dimensional Computed Tomography.
AB - Morphometric analysis of the mandibular ramus (MR) provides highly accurate data
to discriminate sex. The objective of this study was to demonstrate the utility
and accuracy of MR morphometric analysis for sex identification in a Turkish
population.Four hundred fifteen Turkish patients (18-60 y; 201 male and 214
female) who had previously had multidetector computed tomography scans of the
cranium were included in the study. Multidetector computed tomography images were
obtained using three-dimensional reconstructions and a volume-rendering
technique, and 8 linear and 3 angular values were measured. Univariate,
bivariate, and multivariate discriminant analyses were performed, and the
accuracy rates for determining sex were calculated.Mandibular ramus values
produced high accuracy rates of 51% to 95.6%. Upper ramus vertical height had the
highest rate at 95.6%, and bivariate analysis showed 89.7% to 98.6% accuracy
rates with the highest ratios of mandibular flexure upper border and maximum
ramus breadth. Stepwise discrimination analysis gave a 99% accuracy rate for all
MR variables.Our study showed that the MR, in particular morphometric measures of
the upper part of the ramus, can provide valuable data to determine sex in a
Turkish population. The method combines both anthropological and radiologic
studies.
PMID- 27513773
TI - Clinical, Morphological, and Molecular Evaluations of Bone Regeneration With an
Additive Manufactured Osteosynthesis Plate.
AB - There is limited information on the biological status of bone regenerated with
microvascular fibula flap combined with biomaterials. This paper describes the
clinical, histological, ultrastructural, and molecular picture of bone
regenerated with patient-customized plate, used for mandibular reconstruction in
combination with microvascular osteomyocutaneous fibula flap. The plate was
virtually planned and additively manufactured using electron beam melting. This
plate was retrieved from the patient after 33 months. Microcomputed tomography,
backscattered-scanning electron microscopy, histology, and quantitative
polymerase chain reaction were employed to evaluate the regenerated bone and the
flap bone associated with the retrieved plate. At retrieval, the posterior two
thirds of the plate were in close adaptation with the underlying flap, whereas
soft tissue was observed between the native mandible and the anterior one-third.
The histological and structural analyses showed new bone regeneration, ingrowth,
and osseointegration of the posterior two-thirds. The histological observations
were supported by the gene expression analysis showing higher expression of bone
formation and remodeling genes under the posterior two-thirds compared with the
anterior one-third of the plate. The observation of osteocytes in the flap
indicated its viability. The present data endorse the suitability of the
customized, additively manufactured plate for the vascularized fibula mandibular
reconstruction. Furthermore, the combination of the analytical techniques
provides possibilities to deduce the structural and molecular characteristics of
bone regenerated using this procedure.
PMID- 27513775
TI - Le Fort I Disassembly for the Management of Juvenile Ossifying Fibroma Extending
To the Skull Base.
AB - Ossifying fibroma is a rare benign osteogenic neoplasm arising from
undifferentiated cells of the periodontal ligament. Ossifying fibroma have a well
defined border that differentiates it from fibrous dysplasia clinically; these
tumors manifest as a round or ovoid, expansile, painless, slow-growing mass may
displace the roots of adjacent teeth and also cause root resorption. A variety of
approaches for resection of the maxilla have been described. Most involve the use
of facial and lip-splitting incisions to gain wide access. Surgical approach
specifically to the ossifying fibroma located in the midface includes the Le Fort
I approach, Caldwell-Luc access, lateral rhinotomy with medial or total
maxillectomy, external ethmoidectomy, and endoscopic surgery. The access through
Le Fort I disassembly is a versatile approach not only because of the aesthetic
potential in using intraoral incision but also due to its minimal invasiveness,
lesser complications and gives the possibility of reconstruction in a single
operation. Le Fort I disassembly followed by an excision appears to be a
versatile, secure, and satisfactory option.
PMID- 27513777
TI - A New Method of Directing Endoscope Pathway in Single-Nostril Transpheoidal
Approach for Safety by Using Volume Rendering With Thin-Section Computed
Tomographic Image.
AB - OBJECTIVE: This study aims to locate important structures surrounding the sella
node and measure the distances and angles between signalized points by using both
three-dimensional reconstruction technique and volume-rendering. These distances
and angles can provide more accurate reference for surgeries in pituitary
adenomas. METHODS: Ninty volunteers' skulls were scanned and thin-section
computed tomographic images were displayed. The highest point of saddle node on
double sides were marked as point A (right) and A1 (left), the highest point of
posterior Clinton process on double side as B (right) and B1 (left). And the
point of alas minor ossis sphenoridalis with sohenoidal creast was marked as
point O. For the latter can not been distinguished in images, point O was used to
replace the anterior nasal spine, which can accurately locate the median sagittal
plane. The result of three-dimensional reconstruction is used to measure the
distance between O and A, A1, B, B1 and angles between OA, OA1, OB, OB1 and their
projection line on the standard horizontal plane (alpha, alpha1, beta, beta1).
Analyzing the difference by examining the significance difference between both
sides can also help the authors to determine whether there is a symmetric
difference. RESULTS: The distance of OA was measured as 23.2 (6.5) mm [range,
11.2-45.2 mm; 95% confidence interval (CI), 21.9-24.4 mm]. The distance of OA1
was measured as 23.4 (5.7) mm (range, 9.9-47.2 mm; 95% CI, 22.2-24.6 mm). The
distance of OB was measured as 31.1 (5.5) mm (range, 17.8-45.2 mm; 95% CI, 30.0
32.2 mm). The distance of OB1 was measured as 31.2 (6.0) mm (range, 10.1-47.8 mm;
95% CI, 30.0-32.5 mm). The angle of alpha was measured as 81.1 (10.0) degrees
(range, 60-137.5 degrees , 95% CI, 79.0-83.2 degrees ). The angle of alpha1 was
measured as 81.3 (8.5) degrees (range, 60-97.4 degrees , 95% CI, 79.5-83.1
degrees ). The angle of beta was measured as 91.5 (5.2) degrees (range, 74.9
102.2 degrees , 95% CI, 90.5-92.6 degrees ). The angle of beta1 was measured as
91.0 (6.6) degrees (range, 74.7-104.7 degrees , 95% CI, 89.2-92.0 degrees ).
CONCLUSIONS: The above results can facilitate the location of these structures
and minimize surgical trauma to optic chiasm and carotid artery surrounding. The
method is especially effective in promising more secure and accurate direction to
guide surgeons during surgeries in pituitary adenomas.
PMID- 27513779
TI - Possibility of Using Standard Plates for Orbital Fracture.
AB - OBJECTIVES: Absorbable plates are sometimes grafted for treating orbital
fractures. These plates cannot be readily processed to fit the shape of the
fracture site, particularly when the fracture encompasses a broad area from the
medial toward the inferior wall. Preparing the plates in a standard shape
beforehand will be useful. Thus, in this study, the authors measured the orbital
wall distance in healthy orbits to determine the mean orbital size with the
ultimate goal of developing and clinically applying a standard plate for orbital
fracture. METHODS: Measurements were performed for the left eye orbit on computed
tomography images using a three-dimensional medical image processing workstation.
The authors measured the orbital wall distances and angle of healthy orbits in 40
males and 40 females to determine the mean size of the orbit. RESULTS: In healthy
orbits, no significant difference was noticeable in the angle between medial wall
and inferior wall between males and females. The medial, inferior, and medial +
inferior wall distances were markedly longer in males than in females (P < 0.05).
DISCUSSIONS: The orbital shapes had the same pattern in males and females. The
standard plate would be adaptable to all cases if it were produced with the
medial wall + inferior wall distance greater than the maximum value in males and
trimmed to fit the orbit form of the patient. CONCLUSIONS: The results would be
the basis of creating a standard plate and using it after appropriate
adjustments.
PMID- 27513780
TI - Temporal High-Resolution Computed Tomography and Magnetic Resonance Imaging of
Congenital Inner Ear Anomalies in Children.
AB - Imaging plays an important role in determining indications of cochlear
implantation and choosing candidates for the procedure in children. Temporal high
resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) can
display precisely the complex anatomic structure of inner ear. Although HRCT
permits detailed imaging of bony structures, MRI gives valuable information about
membranous labyrinth, internal acoustic canal, and vestibulocochlear nerve.
Magnetic resonance imaging examination of the brain should be performed at the
same time to evaluate any coexistent brain parenchymal abnormality. These imaging
modalities are complementary methods in evaluating congenital inner ear
anomalies. The aim of this pictorial essay is to reviewing temporal HRCT and MRI
findings of congenital inner ear anomalies.
PMID- 27513781
TI - Chondromatosis of the Temporomandibular Joint as a Consequence of Persistent Long
Lasting Joint Dysfunction: Late Diagnosis of a Rare Occurrence.
AB - The authors present a rare patient of right synovial chondromatosis (SC) of the
temporomandibular joint in which diagnosis was late and delay led to SC extension
to the cranial base. Synovial chondromatosis is a rare benign disorder
characterized by multiple cartilaginous free-floating nodules originated from the
synovial membrane of large articular joints of the body. Differential diagnosis
is with neoplasm and radical surgical removal is essential. The patient came to
the authors' observation complaining about long-lasting temporomandibular joint
dysfunction. The patient already underwent either functional or medical therapy
in times without any improvement. Clinical examination showed limited mouth
opening and swelling of the right preauricolar region with no signs of facial
nerve palsy and without paresthesia or hearing loss. No history of recent trauma
was recorded. Magnetic resonance imaging showed a mucous-like hyperintense mass
with small hypointense spots inside. A preoperative computed tomography scan was
performed and showed a mass extending from the superior aspect of the
temporomandibular joint to the glenoid fossa, which was partially eroded. The
patient underwent either open joint surgery or arthroscopy of the superior joint
space and a large number of chondrocytes were removed. No complications were
recorded postoperatively and the patient completely recovered after 6 months.
Histology confirmed the diagnosis of synovial condromatosys of the right
temporomandibular joint.
PMID- 27513782
TI - Positional Relationship of Ethmoidal Foramens With Reference to the Nasion and
Its Significance in Orbital Surgery.
AB - PURPOSE: The aim of the study was to elucidate the positional relationship of the
ethmoidal foramens (EFs) with reference to the nasion to facilitate prediction of
the exact location of EFs, the optic canal (OC), and the frontoethmoidal suture
(FS), and thereby avoid complications during complex surgery involving the medial
wall of the orbit. MATERIALS AND METHODS: One hundred two intact orbits of 57
embalmed cadavers were dissected in this observational anatomic study. Nasion'
(N') was defined as the intersection point of the medial orbit margin with the
horizontal line through the nasion, and this was used as a reference point. N'-OC
was defined as the straight line joining N' and OC. The locations of the anterior
ethmoidal foramen (AEF), posterior ethmoidal foramen (PEF), and OC were
determined with reference to N'. The vertical distances from N'-OC to EFs and to
FS were also determined. RESULTS: The N'-AEF, AEF-PEF, and PEF-OC distances were
18.4, 15.3, and 8.3 mm, respectively. Vertically, AEF and PEF were situated at
0.2 mm below and 0.4 mm above N'-OC, respectively. At the same reference points,
N'-OC was situated at 0.4 and 0.6 mm above FS, respectively. CONCLUSIONS: N',
AEF, PEF, and OC were considered to be situated on the same straight line, and N'
OC could be regarded as coinciding with FS. This means that N' is an easily
identifiable and reliable landmark for identifying EFs, OC, and FS. Our
navigational parameters with reference to N' will help surgeons to enhance the
safety of orbital surgery.
PMID- 27513783
TI - Excellent Result With the Use of Single-Dose OK-432 in Cervical Macrocystic
Lymphangioma.
AB - Though the lymphangioma is a benign neoplasm, it may make an invasion to vital
structures by progressively growing. For lymphangioma, which progressed in such a
way, surgical treatment has high morbidity and recurrence risk. On these cases,
OK-432 is a frequently used sclerotherapy agent. The authors report the result
they obtained by the use of single-dose OK-432 on an inoperable pediatric
cervical macrocystic lymphangioma case and also their experiences.
PMID- 27513784
TI - The Effects of Nigella Sativa Seed Extract on Bone Healing in an Experimental
Model.
AB - The purpose of this study was to histologically evaluate the effects on bone
healing of nigella sativa seed extract applied on calvarial defects in an
ovariectomized rat model. The study included 32 female rats weighing 280 to 310 g
with an average age of 3 months. A defect was created with a trephine burr on
each rat calvarium. The rats were divided into 2 groups (control and study) of 8
animals each. All the defects were grafted with a gelatin sponge mixed with
normal saline. In the study group, nigella sativa seed extract was applied
systemically using an oro-gastric tube. Half of the animals in each group were
sacrificed after 2 weeks, and the others after 4 weeks. In the control groups,
the defects were not completely filled with regenerated bone. Osteoblast cells
were observed more in the study groups. A higher rate of osteoclasts was
determined in the control groups. In addition, the nigella sativa group had a
statistically greater amount of bone formation than the others group at both 2
weeks and 4 weeks (P <0.05). The systemic application of nigella sativa seed
extract demonstrated incredibly positive effects on enhanced bone healing in this
experimental osteoporotic model.
PMID- 27513785
TI - Rehabilitation With Mandibular Implant-Retained Complete Overdenture Using the
Association of Two Retention Systems.
AB - This article reports a case of oral rehabilitation with two-implant-retained
mandibular overdenture using bar/clip and ball attachment bilaterally on the
distal side. A patient aged 69 years, fully edentulous, presented herself to
private practice complaining about the instability of mandibular denture. Several
possibilities of rehabilitation with advantages and disadvantages were explained
to the patient, based in the clinical and radiograph examinations, and patient
desire, in which she opted by conventional maxillary complete denture and two
implant-retained mandibular overdenture. Two external hexagon implants of 3.75 *
10 mm were placed in anterior area of mandible. The fabrication of the metal
framework with bar/clip and ball attachment bilaterally on the distal side was
planned based on prior arrangement of the artificial teeth. Internal adaptation
and occlusal adjustments were performed in the day of insertion of finalized
denture and instructions about maintenance and sanitation. The patient showed
satisfaction with the final result of her treatment, and no complications were
observed during this period. The association of bar/clip with ball system may be
viable as option of retention for mandibular implant-retained complete
overdenture; however, further randomized controlled trials are necessary to
obtain detailed knowledge about the topic.
PMID- 27513786
TI - Foreign Body in the Nasal Septum: Lyodura Extrusion.
AB - In otorhinolaryngologic fields, Lyodura had been used mainly in otological
procedures, such as tympanoplasty, myringoplasty, and mastoidectomy. However, so
far in rhinologic area, there is only 1 report that Lyodura was used for closure
of cerebrospinal fluid leaks. This report describes a 54-year-old woman presented
with recurrent purulent discharge for 4-month duration because of Lyodura
extrusion from the septum. On the basis of authors' experience, the authors
highlight that the complete removal of exposed Lyodura from the nasal septum may
be difficult because of adhesion to the surrounding septal mucosal flap. So, the
authors suggest unilaterally wide mucosal incision using mucosal defect site may
be necessary for completely removing Lyodura.
PMID- 27513787
TI - A Primary Cerebellar Glioblastoma Multiforme Mimicking Vestibular Schwannoma.
AB - Cerebellar glioblastoma multiforme (cGBM) is rare in adults, accounting for <1%
of all patients with glioblastoma multiforme (GBM). The accurate diagnosis of
cGBM is important for establishing a suitable therapeutic schedule. However, the
diagnosis of cerebellar GBM is not usually suspected preoperatively because of
its rarity. Generally, patients with cGBMs typically presented with symptoms of
raised intracranial pressure, and infrequently cerebellar symptoms such as gait
ataxia and disequilibrium. Nevertheless, the authors reported a cGMB patient,
with his clinical presentations and imaging characteristics mimicking a
vestibular schwannoma. To the best of our knowledge, this is the first reported
patient with cGBM mimicking a vestibular schwannoma. Furthermore, the diagnosis,
treatment, and prognosis for cGBM were broadly investigated.
PMID- 27513788
TI - Finger rolls: an improvised applicator for atraumatic, sterile application of
finger tourniquets.
PMID- 27513789
TI - Adult distal radius fractures classification systems: essential clinical
knowledge or abstract memory testing?
AB - Classification systems should be tools for concise communication, which ideally
can predict prognosis and guide treatment. They should be relevant, reproducible,
reliable, properly validated and most importantly simple to use and understand.
There are 15 described distal radius classification systems present in the
literature in the past 70 years, of which 8 are discussed in this paper. For each
classification, we give an insight into its history, strengths and weaknesses,
and provide evidence from the literature on reliability and reproducibility.
Sadly, on completion of this paper we have not found a distal radius fracture
classification that proved to be useful. Failings range from poor reproducibility
and reliability, and over-complexity mainly emanating from the inability to
classify this spectrum of injury in all of its manifestations. Consequently, we
would suggest that classification systems for acute adult distal radius fractures
are not useful clinical knowledge but mainly historical and/or research tools.
Moreover, we would discourage trainees from spending time learning these
classifications, as they serve not as essential clinical knowledge but more as
forms of abstract memory testing.
PMID- 27513790
TI - Operative treatment of calcaneal fractures: improved outcomes and low
complications rates with a strict management protocol.
AB - This is a retrospective review of 80 intra-articular calcaneal fractures treated
with open reduction and internal fixation by a specialist team under supervision
of a single surgeon in a tertiary centre between 2005 and 2014. The fractures
were evaluated with plain radiography and computed tomography, and graded using
the Eastwood-Atkins classification. A lateral approach was used and all fractures
were fixed with calcaneal plates. All patients had clinical and radiological
follow-up. Clinical assessment included foot and ankle disability index, SF-36(r)
and Kerr-Atkins scores. The mean follow-up duration was 72 months (range: 12-130
months). The mean age of patients was 49 years (range: 17-73 years). There were
three open fractures and eight patients had other injuries. The mean Bohler's
angle improved from 6 degrees preoperatively to 26 degrees postoperatively. The
mean foot and ankle disability index score was 78.62, the mean SF-36(r) scores
were 45.5 (physical component) and 52.6 (mental component), and the mean Kerr
Atkins score was 72 (range: 36-100). Early complications included one case of
screw protrusion in the subtalar joint (which warranted a repeat procedure), one
sural nerve injury and one wound breakdown, which healed with non-operative
measures. Twelve patients had symptomatic subtalar joint osteoarthritis. Four of
these had subtalar fusion. We believe that our strict protocols of patient
selection, intraoperative and postoperative management produced long-term results
comparable with those in the peer reviewed literature.
PMID- 27513791
TI - Adult respiratory distress syndrome.
AB - Adult respiratory distress syndrome (ARDS) has now been described as a sequela to
such diverse conditions as burns, amniotic fluid embolism, acute pancreatitis,
trauma, sepsis and damage as a result of elective surgery in general. Patients
with ARDS require immediate intubation, with the average patient now being
ventilated for between 8 and 11 days. While the acute management of ARDS is
conducted by the critical care team, almost any surgical patient can be affected
by the condition and we believe that it is important that a broader spectrum of
hospital doctors gain an understanding of the nature of the pathology and its
current treatment.
PMID- 27513792
TI - Venous thromboembolism after total knee replacement or total hip replacement:
what can be learnt from root-cause analysis?
AB - INTRODUCTION Because of the high risk of venous thromboembolism (VTE) in total
hip replacement (THR) and total knee replacement (TKR), guidelines are used
widely to enhance effective (yet safe) prophylaxis. If patients develop VTEs
despite use of such guidelines, then the reasons are that the guidelines were:
(i) followed but the VTE occurred anyway; (ii) not implemented appropriately. All
VTEs are assessed routinely by root-cause analysis (RCA). METHODS The records and
subsequent RCA reports for each patient who experienced clinically significant
VTE after THR or TKR were reviewed. We established adherence to the guidelines
(deemed to be 'unavoidable' with scope to improve the guidelines) and non
adherence (deemed to be 'avoidable' with scope to improve implementation).
RESULTS Of 2,214 patients undergoing THR (n=1,330) or TKR (n=884), 25 (1.13%)
experienced VTE. Four THR patients experienced VTE (2 of which were avoidable)
and 21 TKR patients experienced VTE (5 of which were avoidable). There were
significantly more VTEs in TKR patients than THR patients (p<0.0001). CONCLUSIONS
A proportion of patients will experience VTE even if guidelines are followed (a
baseline effect). Administration of chemical prophylaxis earlier might reduce
this baseline effect further. This approach should be taken cautiously with due
respect for the alternative risk of bleeding. Improvement in hospital routine may
reduce the risk of VTE yet further.
PMID- 27513793
TI - A method for performing intraoperative enteroscopy.
PMID- 27513794
TI - Difficult urethral catheterisation made safer: visualising the 'blind'
hydrophilic wire.
PMID- 27513795
TI - Laparoscopic use of a 90-degree cross-stapling device for low rectal division.
PMID- 27513796
TI - Subchondral bone purchase can aid femoral head extraction.
PMID- 27513797
TI - Characteristics and computed tomography evaluation of primary retroperitoneal
tumours: report of 113 cases.
AB - INTRODUCTION Benign and malignant primary retroperitoneal tumours (PRT) have
different clinical manifestations and pathological characteristics. We explore
the characteristics and evaluate the value of computed tomography (CT) for PRT.
METHODS Fifty-six benign and fifty-seven malignant PRT with clinical,
radiographic and surgical data were retrospectively investigated. Statistical
analysis was carried out using SPSS software. RESULTS We found that mean size of
benign tumours was 12.4 +/- 7.7cm but 20.7 +/- 11.6cm in malignant cases (P <
0.05). The accuracy of CT localisation was approximately 70%. The sensitivity and
specificity of CT diagnosis for benign tumours were 96% and 85%, respectively; 51
(91%) underwent complete resection among benign cases but 42 (74%) in malignant
cases (P < 0.05). Sensitivity of CT evaluation for invaded organs and vessels was
50% and 65%, respectively, and specificity was 88% and 81%, respectively.
CONCLUSIONS Large size, no capsule, irregular margin, heterogeneous density and
specific enhancement pattern on CT are highly suggestive of malignancy. CT is the
most useful tool in assessing the size and characteristics of PRT but it does not
have the sensitivity to assess the involvement of organs and vessels.
PMID- 27513798
TI - Outcomes of regional transfers of ruptured abdominal aortic aneurysm in a UK
vascular network.
AB - INTRODUCTION Rupture of abdominal aortic aneurysm is a surgical emergency. In
order to improve operative outcomes, vascular services have been centralised in
the United Kingdom. This means that a patient may present to a hospital with a
ruptured aneurysm, but require transfer to a vascular centre for definitive
treatment. METHODS This retrospective cohort study identified patients who
underwent surgery for ruptured abdominal aortic aneurysm in a tertiary vascular
centre over a 2-year period. Data on demographics and originating unit were
recorded. Outcomes assessed included 30-day mortality, operative mortality and
postoperative morbidity. RESULTS We identified 70 patients who underwent surgery
for ruptured abdominal aortic aneurysm in the 2-year period; 36 presented
directly to the vascular unit (VU), 14 to referral unit 1 (RU1) and 20 to
referral unit 2 (RU2); 30-day mortality rates were 27.7% (VU), 35.5% (RU1) and
30.0% (RU2), respectively. There was no statistical difference in mortality
between units. Postoperative complications were seen in 35.9% of VU patients,
78.6% of RU1 patients and 70% of RU2 patients. This was statistically significant
between VU and RU1 (P = 0.006) and VU and RU2 (P = 0.02). Direct operative
complications were seen in 9 patients, gastrointestinal complications in 9, limb
complications in 6 and systemic complications in 40. CONCLUSION This study found
that site of presentation does not affect mortality but is associated with
increased morbidity. This is a complex issue, which will require a prospective
multicentre study to investigate further.
PMID- 27513799
TI - Cellacast(r) Splint as an adjunct to postoperative neck dressings for burns
patients.
PMID- 27513801
TI - Tensioned fine wire for proximal femur traction table reduction in amputees.
PMID- 27513800
TI - Initial UK experience with transversus abdominis muscle release for posterior
components separation in abdominal wall reconstruction of large or complex
ventral hernias: a combined approach by general and plastic surgeons.
AB - Introduction Large, complicated ventral hernias are an increasingly common
problem. The transversus abdominis muscle release (TAMR) is a recently described
modification of posterior components separation for repair of such hernias. We
describe our initial experience with TAMR and sublay mesh to facilitate abdominal
wall reconstruction. Methods The study is a retrospective review of patients
undergoing TAMR performed synchronously by gastrointestinal and plastic surgeons.
Results Twelve consecutive patients had their ventral hernias repaired using the
TAMR technique from June 2013 to June 2014. Median body mass index was 30.8kg/m2
(range 19.0-34.4kg/m2). Four had a previous ventral hernia repair. Three had
previous laparostomies. Four had previous stomas and three had stomas created at
the time of the abdominal wall reconstruction. Average transverse distance
between the recti was 13cm (3-20cm). Median operative time was 383 minutes (150
550 minutes) and mesh size was 950cm2 (532-2400cm2). Primary midline fascial
closure was possible in all cases, with no bridging. Median length of hospital
stay was 7.5 days (4-17 days). Three developed minor abdominal wall wound
complications. At median review of 24 months (18-37 months), there have been no
significant wound problems, mesh infections or explants, and none has developed
recurrence of their midline ventral hernia. Visual analogue scales revealed high
patient satisfaction levels overall and with their final aesthetic appearance.
Conclusions We believe that TAMR offers significant advantages over other forms
of components separation in this patient group. The technique can be adopted
successfully in UK practice and combined gastrointestinal and plastic surgeon
operating yields good results.
PMID- 27513802
TI - A novel method for practising local skin flaps.
PMID- 27513803
TI - Serious tonsil infections versus tonsillectomy rates in Wales: A 15-year
analysis.
AB - INTRODUCTION Sore throat and tonsillitis place a significant burden on the
National Health Service. National guideline criteria for gauging the severity of
sore throat and tonsillitis have reduced the number of tonsillectomies performed,
which is thought to have increased the rate of tonsil-related infections. METHODS
Data was extracted from the prospective Patient Episode Database of Wales and
analysed to determine the annual number of tonsillectomies for recurrent
tonsillitis, adjusted for population changes. Admissions to acute hospitals for
tonsillitis, peritonsillar abscess and deep neck space abscesses were also
examined. RESULTS Between 1999 and 2014, hospital admissions for tonsillitis rose
three-fold (r=0.968), while admissions for peritonsillar abscess rose by 48%
(r=0.857) and retro or parapharyngeal abscess admissions also increased
(r=0.709). In contrast, the number of tonsillectomies per 100,000 population
gradually decreased (r=-0.16). There was a positive correlation between the
incidence of tonsillitis and admissions for peritonsillar abscess (adjusted r2
0.631; p=0.015) and retropharyngeal abscess (adjusted r2 0.442; p=0.00254). There
was a statistically significant negative correlation between the incidence of
tonsillitis and the number of tonsillectomies performed (adjusted r2=-0.07;
p=0.0235). CONCLUSIONS The significant rise in tonsillitis in Wales raises the
question as to whether we should revisit the criteria for tonsillectomy. The
perceived cost saving from limiting certain procedures should not prevent
healthcare policymakers from considering all other evidence. The rise in
peritonsillar, retropharyngeal and parapharyngeal abscess is alarming, as they
are associated with significant morbidity and mortality.
PMID- 27513804
TI - A novel technique for the explantation of a cemented femoral hip prosthesis.
PMID- 27513805
TI - Aorto-oesophageal fistula after oesophageal stent placement in a patient with a
Roux-en-Y gastric bypass.
AB - A 43-year-old female patient suffered from persistent anastomotic leakage after
Roux-en-Y gastric bypass for morbid obesity. Endoscopic stenting of the
anastomotic leakage was performed. The patient presented with haematemesis 3
weeks later. An aorto-oesophageal fistula was diagnosed, most likely due to
ulceration of the oesophageal stent. The fistula was closed with an endovascular
covered aortic stent and a new gastrojejunostomy was created. One year after
surgery, the patient is in good condition. Endoscopic stents are increasingly
being used to treat anastomotic leakage in bariatric patients. An aorto
oesophageal fistula is a life-threatening complication of stent placement, early
clinical recognition is essential. More data are needed on the complications of
anastomotic stenting in bariatric patients.
PMID- 27513806
TI - Natural variation in maternal sensitivity is reflected in maternal brain
responses to infant stimuli.
AB - Increasing evidence suggests that discrete neural networks that mediate emotion
processing are activated when mothers respond to infant's images or cries.
Accumulating data also indicate that natural variation in maternal caregiving
behavior is related to maternal oxytocin (OT) levels. However, brain activation
to infant cues has not been studied comparing mothers at disparate ends of the
"maternal sensitivity" spectrum. Based on observed mother-infant play interaction
at 4-6 months postpartum in 80 antenatally recruited mothers, 15 mothers with the
highest sensitivity (HSMs) and 15 mothers with the lowest sensitivity (LSMs) were
followed at 7-9 months using functional magnetic resonance imaging (fMRI) to
examine brain responses to viewing videos of their "own" versus an "unknown"
infant in 3 affect states (neutral, happy, and sad). Plasma OT measurements were
taken from mothers following play interactions with their infant. Compared with
LSMs, HSMs showed significantly greater brain activation in right superior
temporal gyrus (STG) in response to own versus unknown neutral infant and to own
happy versus neutral control. Changes in brain activation were significantly
negatively correlated with plasma OT responses in HSMs mothers. Conversely,
compared with HSMs, LSMs showed no significant activation difference in response
to own infant separately or in contrast to unknown infant. Activation of STG may
index sensitive maternal response to own infant stimuli. Sensitive parenting may
have its unique profile in relation to brain responses which can act as
biomarkers for future intervention studies that enhance sensitivity of maternal
care. (PsycINFO Database Record
PMID- 27513807
TI - Blocking serotonin but not dopamine reuptake alters neural processing during
perceptual decision making.
AB - Dopamine and serotonin have opponent interactions on aspects of impulsivity.
Therefore we wanted to test the hypothesis that dopamine and serotonin would have
opposing effects on speed-accuracy trade offs in a perceptual decision making
task. Unlike other behavioral measures of impulsivity, perceptual decision making
allows us to determine whether decreasing premature responses, often interpreted
as decreased impulsivity, corresponds to increased behavioral performance. We
administered GBR-12909 (a dopamine transporter blocker), escitalopram (a
serotonin transporter blocker), or saline in separate sessions to 3 rhesus
macaques. We found that animals had slower reaction times (RTs) on escitalopram
than on GBR-12909 or saline. However, they were also least accurate on
escitalopram. Animals were faster, although nonsignificantly, on GBR than saline
and had equivalent accuracy. Administration of GBR-12909 did cause animals to be
faster in error trials than correct trials. Therefore, from the point of view of
RTs the animals were less impulsive on escitalopram. However, the decreased
accuracy of the monkeys shows that they were not able to make use of their slower
response times to make more accurate decisions. Therefore, impulsivity was
reduced on escitalopram, but at the expense of a slower information-processing
rate in the perceptual inference task. (PsycINFO Database Record
PMID- 27513808
TI - Amine-Appended Hierarchical Ca-A Zeolite for Enhancing CO2 /CH4 Selectivity of
Mixed-Matrix Membranes.
AB - An amine-appended hierarchical Ca-A zeolite that can selectively capture CO2 was
synthesized and incorporated into inexpensive membrane polymers, in particular
polyethylene oxide and Matrimid, to design mixed-matrix membranes with high CO2
/CH4 selectivities. Binary mixture permeation testing reveals that amine-appended
mesoporous Ca-A is highly effective in improving CO2 /CH4 selectivity of
polymeric membranes. In particular, the CO2 /CH4 selectivity of the polyethylene
oxide membrane increases from 15 to 23 by incorporating 20 wt % amine-appended Ca
A zeolite. Furthermore, the formation of filler/polymer interfacial defects,
which is typically found in glassy polymer-zeolite pairs, is inhibited owing to
the interaction between the amine groups on the external surface of zeolites and
polymer chains. Our results suggest that the amine-appended hierarchial Ca-A,
which was utilized in membrane fabrication for the first time, is a good filler
material for fabricating a CO2 -selective mixed-matrix membrane with defect-free
morphology.
PMID- 27513809
TI - Does dentifrice use help to remove plaque? A systematic review.
AB - AIMS: The aim of this systematic review was to establish the efficacy of brushing
with and without a dentifrice for dental plaque removal. MATERIALS AND METHODS:
MEDLINE-PubMed, Cochrane-CENTRAL, EMBASE and other electronic databases were
searched. The inclusion criteria were randomized controlled trials and controlled
clinical trials and subjects >=18 years of age with good general health. Studies
that evaluated the effect of toothbrushing with a dentifrice compared to brushing
without a dentifrice were included. Data were extracted from the eligible
studies, and a meta-analysis was performed where feasible. RESULT: The search was
conducted until June 2016 and retrieved 10 eligible publications that included 20
comparisons. On average, 49.2% of plaque was removed when brushing was performed
with a dentifrice, and 50.3% of plaque was removed when toothbrushing was
performed without a dentifrice. The descriptive analysis indicated that the
majority of the comparisons did not show an additional effect of dentifrice use.
Regarding the meta-analysis of post-brushing scores, no significant difference
was observed between toothbrushing with and without a dentifrice (DiffM 0.00,
95%CI [-0.05: 0.05], p = 0.91). The meta-analysis of incremental data (as means
or percentages) supported and strengthened these findings. CONCLUSION: The
cumulative evidence for this systematic review demonstrates that there is
moderate certainty that toothbrushing with a dentifrice does not provide an added
effect for the mechanical removal of dental plaque.
PMID- 27513810
TI - Characteristics of Metabolic Syndrome in Morbidly Obese Subjects.
AB - BACKGROUND: Metabolic syndrome (MetSyn) magnifies risks of cardiovascular disease
(CVD) and type 2 diabetes, but its expression varies within the obese population.
We examined body mass index (BMI), metabolic traits, and fat distribution in
morbidly obese individuals. METHODS: Lipids and inflammatory, oxidative stress
and hepatic biomarkers in 346 women and 203 men (BMI >=35 kg/m2 and co-morbidity
or >=40 kg/m2) were stratified by MetSyn components (1-5, excluding diabetes).
Age- and smoking-adjusted partial correlations were calculated. Dual-energy X-ray
absorptiometry was measured in 206 participants. RESULTS: Apolipoprotein B,
ferritin, uric acid, and alanine aminotransferase (ALT) concentrations worsened
with increasing MetSyn components (P <= 0.0001), while BMI and LDL-cholesterol
showed no association. BMI correlated inversely with triglycerides (r = -0.16, P
= 0.03) and positively with HDL-cholesterol in men (r = 0.16, P = 0.02), but not
in women. BMI correlated with C-reactive protein (CRP) (r = 0.32, P < 0.0001; r =
0.24, P < 0.0001 in men and women, respectively) and white blood cell count (r =
0.24, P = 0.001 in men; r = 0.15, P = 0.008 in women). Truncal fat percentage
correlated to CRP (r = 0.31, P = 0.03; r = 0.20, P = 0.02 in men and women,
respectively). In women, number of MetSyn components was inversely related to
truncal and peripheral fat (r = -0.20, P = 0.02; r = -0.42, P < 0.0001,
respectively) as was ALT (r = -0.21, P = 0.009; r = -0.38, P < 0.0001,
respectively) and triglycerides with peripheral fat (r = -0.38, P < 0.0001),
while HDL cholesterol was positively associated with truncal and peripheral fat
(r = 0.26; P = 0.001). CONCLUSIONS: BMI and fat distribution showed expected
associations to inflammation biomarkers, but paradoxical relations between fat
indices, and MetSyn components and biomarkers were seen. This suggests a need for
better markers of CVD risk in morbid obesity.
PMID- 27513811
TI - Green fluorescent protein chromophore derivative suppresses ultraviolet A-induced
JNK-signalling and apoptosis in keratinocytes and adverse effects in zebrafish
embryos.
AB - Solar ultraviolet (UV) light has been recognized as the important environmental
hazard and contributes to diverse skin damage such as cell death, photoageing and
even carcinogenesis. Revelation of harmful responses attributed to UVA radiation
has promoted the development of photoprotective agents against UVA-induced skin
damage. In the present study, we tried to evaluate the potential protective
effects of a synthetic green fluorescent protein (GFP) chromophore derivative, 4
chlorobenzyldene-1, 2-dimethylimidazolinone (Cl-BDI, called TC-22) on UVA- and
UVB- induced stress responses in skin. The HaCaT keratinocytes were used to
evaluate the cellular effects. Zebrafish (Danio rerio), which is regarded as a
useful and cost-effective alternative to some mammalian models, was applied as
the in vivo animal model. In HaCaT keratinocytes, TC-22 was able to obviously
decrease UVA-induced cell death. Dissection of the UVA-induced signalling
pathways revealed that TC-22 could suppress the activation of JNK and caspase 3,
but not of ERK and p38. Reduction of UVA-induced cleavage of caspase 3 and sub-G1
phase accumulation by pretreatment of TC-22 was also observed. In zebrafish, we
showed that UVA irradiation could decrease the survival and hatching rate,
suppress heart beats of embryos and enhance the pigmentation of larvae.
Pretreatment of TC-22 could significantly reverse UVA-induced the suppression in
hatching of eggs and heart beating of embryos and also lowered the UVA-induced
pigmentation in zebrafish. Collectively, we demonstrate that TC-22, a GFP
chromophore derivative, can ameliorate the UVA-induced stress responses in both
epidermal keratinocytes and zebrafish, suggesting the potential use of TC-22 in
photoprotection in the future.
PMID- 27513812
TI - Second Generation of Aldol Reaction.
AB - Since the discovery of the Mukaiyama aldol reaction more than 40 years ago,
several landmark publications have inspired researchers in the field. The
Mukaiyama AR is one of the most significant named reactions in organic synthesis.
In the past few decades, development of the modern AR has been at the forefront
in addressing the challenges of regio-, chemo-, diastereo-, and
enantioselectivity in organic synthesis. All of these selectivity challenges
maybe present in a single pair of reactants, thus controlling the outcome of such
a process has great practical value. More than 10 years ago, our group became
involved in this iconic carbon-carbon bond-forming process and attempted to very
closely investigate all possible features of the AR to solve several issues still
encountered by chemists, most notably the selectivity challenges mentioned above.
In this context, our group initiated the second generation of the AR based on a
Lewis or Bronsted acid-catalyzed process in conjunction with the use of a "super
silyl" (tris(trimethylsilyl)silyl) directing group, which has demonstrated
unrivalled properties in controlling the outcome of the AR. Using the
extraordinary power of the super silyl group, we were able to develop new methods
and concepts that broadly impacted the ability to control the selectivity
attributes and thus allowed for a highly stereoselective construction of
polyketide, halogenated polyketide, polypropionate, and polyol scaffolds through
inter- and/or intramolecular aldolization protocols. Our diastereoselective ARs
of super silyl enol ethers and aldehydes have shown great efficiency and
modularity in producing exclusively and preferentially syn- or anti-adducts,
creating up to four new adjacent stereocenters in a one-pot sequential manner and
under mild reaction conditions. The super silyl-directed AR does not only provide
a solution to stereochemistry control challenges, but also offers an efficient,
modular and high yielding technique toward nontrivial construction of complex
architectures with unprecedented ease. We believe that the new Lewis- or Bronsted
acid-catalyzed super-silyl-directed AR processes chronicled in our laboratories
have come to maturity and now offer a "road map" for strategic stereoselective
synthesis of polyketide-like units. Herein we report our recent achievements in
the diastereoselective C-C bond formation, through the super-silyl-directed AR,
toward the synthesis of complex and sophisticated hydroxy aldehydes. We would
like to note that due to the extremely broad range of work reported in this
field, only stereoselective AR involving aldehyde-derived super SEEs will be
discussed in this Account.
PMID- 27513813
TI - Synthesis, in vitro and in vivo small-animal SPECT evaluation of novel technetium
labeled bile acid analogues to study (altered) hepatic transporter function.
AB - INTRODUCTION: Hepatobiliary transport mechanisms are crucial for the excretion of
substrate toxic compounds. Drugs can inhibit these transporters, which can lead
to drug-drug interactions causing toxicity. Therefore, it is important to assess
this early during the development of new drug candidates. The aim of the current
study is the (radio)synthesis, in vitro and in vivo evaluation of a technetium
labeled chenodeoxycholic and cholic acid analogue: [(99m)Tc]-DTPA-CDCA and
[(99m)]Tc-DTPA-CA, respectively, as biomarker for disturbed transporter
functionality. METHODS: [99mTc]-DTPA-CDCA([(99m)Tc]-3a) and [99mTc]-DTPA-CA
([(99m)Tc]-3b) were synthesized and evaluated in vitro and in vivo. Uptake of
both tracers was investigated in NTCP, OCT1, OATP1B1, OATP1B3 transfected cell
lines. Km and Vmax values were determined and compared to [(99m)Tc]-mebrofenin
([(99m)Tc]-MEB). Efflux was investigated by means of CTRL, MRP2 and BSEP
transfected inside-out vesicles. Metabolite analysis was performed using pooled
human liver S9. Wild type (n=3) and rifampicin treated (n=3) mice were
intravenously injected with 37MBq of tracer. After dynamic small-animal SPECT and
short CT acquisitions, time-activity curves of heart, liver, gallbladder and
intestines were obtained. RESULTS: We demonstrated that OATP1B1 and OATP1B3 are
the involved uptake transporters of both compounds. Both tracers show a higher
affinity compared to [(99m)Tc]-MEB, but are in a similar range as endogenous bile
acids for OATP1B1 and OATP1B3. [(99m)Tc]-3a shows higher affinities compared to
[(99m)Tc]-3b. Vmax values were lower compared to [(99m)Tc]-MEB, but in the same
range as endogenous bile acids. MRP2 was identified as efflux transporter. Less
than 7% of both radiotracers was metabolized in the liver. In vitro results were
confirmed by in vivo results. Uptake in the liver and efflux to gallbladder +
intestines and urinary bladder of both tracers was observed. Transport was
inhibited by rifampicin. CONCLUSION: The involved transporters were identified;
both tracers are taken up in the hepatocytes by OATP1B1 andOATP1B3 with Km and
Vmax values in the same range as endogenous bile acids and are secreted into bile
canaliculi via MRP2. Dynamic small-animal SPECT imaging can be a useful
noninvasive method of visualizing and quantifying hepatobiliary transporter
functionality and disturbances thereof in vivo, which could predict drug
pharmacokinetics.
PMID- 27513814
TI - Evaluation of the Antihyperglycemic Effect of Minor Steviol Glycosides in
Normoglycemic and Induced-Diabetic Wistar Rats.
AB - Steviol glycosides are a family of compounds found in Stevia rebaudiana Bertoni
that are responsible for sweetness capacity. The antihyperglycemic effect of the
two major steviol glycosides, Rebaudioside A and Stevioside, has been studied and
it has been found that despite having the same common structure, only Stevioside
exerts an antihyperglycemic effect. Although other steviol derivatives are found
in smaller amounts (minor steviol glycosides) in S. rebaudiana, whether or not
they possess antihyperglycemic activity has not been evaluated. The aim of this
study was to evaluate the antihyperglycemic effect of minor steviol glycosides in
normoglycemic and diabetic (streptozotocin/nicotinamide) Wistar rats. Rats were
subjected to an intraperitoneal glucose tolerance test (IPGTT) both before and
after chronic treatment (28 days). After 6 h of fasting, IPGTT was conducted in
pentobarbital-anesthetized rats using 1 g/kg of glucose plus 20 mg/kg of the
minor glycoside (Dulcoside A, Rebaudioside B, C, D, or Steviolbioside) or control
treatment (distilled water, glibenclamide, or metformin); the blood of the tip of
the tail was collected at time 0, 15, 30, 60, and 120 min.; and blood glucose was
measured, and its net area under the curve (AUCnet) was calculated. After 28-day
chronic oral administration, IPGTT was again performed. Differences were
considered significant at P < .05 by one-way ANOVA. Acute intraperitoneal or
chronic oral administration of 20 mg/kg of minor steviol glycosides had no
antihyperglycemic effect in normoglycemic or induced-diabetic Wistar rats.
Considering the dose tested, it is unlikely that these glycosides have an effect
on glucose in diabetic or normoglycemic humans.
PMID- 27513815
TI - Very High Plasma Concentrations of a Monoclonal Antibody against the Human
Insulin Receptor Are Produced by Subcutaneous Injection in the Rhesus Monkey.
AB - Brain penetration of recombinant protein drugs is possible following the re
engineering of the drug as an IgG fusion protein. The IgG domain is a monoclonal
antibody (mAb) against an endogenous blood-brain barrier (BBB) receptor
transporter, such as the insulin receptor. One such mAb targets the human insulin
receptor (HIR) and is active in Rhesus monkeys. Prior work has measured the
plasma pharmacokinetics of HIRMAb-derived fusion proteins following intravenous
(IV) infusion. However, an alternative method of administration for chronic
treatment of brain disease is the subcutaneous (SQ) route. The extent to which an
antibody against the insulin receptor undergoes systemic distribution and
clearance is unknown. Therefore, in the present study, the rate of plasma
clearance of the HIRMAb is measured in Rhesus monkeys following IV or SQ
administration of 3, 10, and 30 mg/kg doses of the antibody. The HIRMAb is
readily absorbed into the systemic circulation following SQ injection with a 42%
plasma bioavailability. The rate of plasma clearance of the antibody, 0.04-0.06
mL/min/kg, is the same following either IV or SQ administration. Owing to the
slow rate of plasma clearance of the antibody, high concentrations of the HIRMAb
are sustained in plasma for days after the SQ injection. The plasma concentration
of the HIRMAb exceeds 0.8 mg/mL, which is 9% of the entire plasma IgG pool in the
primate, after the SQ injection of the high dose, 30 mg/kg, of the antibody. In
summary, the pharmacokinetics of plasma clearance of the HIRMAb are such that
HIRMAb-derived fusion proteins can be developed as protein therapeutics for the
brain with chronic SQ administration on a weekly or twice-weekly regimen.
PMID- 27513816
TI - In Situ Strategy to Encapsulate Antibiotics in a Bioinspired CaCO3 Structure
Enabling pH-Sensitive Drug Release Apt for Therapeutic and Imaging Applications.
AB - Herein we demonstrate a bioinspired method involving macromolecular assembly of
anionic polypeptide with cationic peptide-oligomer that allows for in situ
encapsulation of antibiotics like tetracycline in CaCO3 microstructure. In a
single step one-pot process, the encapsulation of the drug occurs under desirable
environmentally benign conditions resulting in drug loaded CaCO3 microspheres.
While this tetracycline-loaded sample exhibits pH dependent in vitro drug-release
profile and excellent antibacterial activity, the encapsulated drug or the dye
conjugated peptide emits fluorescence suitable for optical imaging and detection,
thereby making it a multitasking material. The efficacy of tetracycline loaded
calcium carbonate microspheres as pH dependent drug delivery vehicles is further
substantiated by performing cell viability experiments using normal and cancer
cell lines (in vitro). Interestingly, the pH-dependent drug release enables
selective cytotoxicity toward cancer cell lines as compared to the normal cells,
thus having the potential for further development of therapeutic applications.
PMID- 27513817
TI - Systems biology insights into the meaning of the platelet's dual-receptor
thrombin signaling.
AB - : Essentials Roles of the two thrombin receptors in platelet signaling are poorly
understood. Computational systems biology modeling was used together with
continuous flow cytometry. Dual-receptor system has wide-range sensitivity to
thrombin and optimal response dynamics. Procoagulant platelet formation is
determined by donor-specific activities of the two receptors. SUMMARY: Background
Activation of human platelets with thrombin proceeds via two protease-activated
receptors (PARs), PAR1 and PAR4, that have identical main intracellular signaling
responses. Although there is evidence that they have different
cleavage/inactivation kinetics (and some secondary variations in signaling), the
reason for such redundancy is not clear. Methods We developed a
multicompartmental stochastic computational systems biology model of dual
receptor thrombin signaling in platelets to gain insight into the mechanisms and
roles of PAR1 and PAR4 functioning. Experiments employing continuous flow
cytometry of washed human platelets were used to validate the model and test its
predictions. Activity of PAR receptors in donors was evaluated by mRNA
measurement and by polymorphism sequencing. Results Although PAR1 activation
produced rapid and short-lived response, signaling via PAR4 developed slowly and
propagated in time. Response of the dual-receptor system was both rapid and
prolonged in time. Inclusion of PAR1/PAR4 heterodimer formation promoted PAR4
signaling in the medium range of thrombin concentration (about 10 nm), with
little contribution at high and low thrombin. Different dynamics and dose
dependence of procoagulant platelet formation in healthy donors was associated
with individual variations in PAR1 and PAR4 activities and particularly by the
Ala120Thr polymorphism in the F2RL3 gene encoding PAR4. Conclusions The dual
receptor combination is critical to produce a response combining three critical
advantages: sensitivity to thrombin concentration, rapid onset and steady
propagation; specific features of the protease-activated receptors do not allow
combination of all three in a single receptor.
PMID- 27513819
TI - Preferential binding of a stable G3BP ribonucleoprotein complex to intron
retaining transcripts in mouse brain and modulation of their expression in the
cerebellum.
AB - Neuronal granules play an important role in the localization and transport of
translationally silenced messenger ribonucleoproteins in neurons. Among the
factors associated with these granules, the RNA-binding protein G3BP1 (stress
granules assembly factor) is involved in neuronal plasticity and is induced in
Alzheimer's disease. We immunopurified a stable complex containing G3BP1 from
mouse brain and performed high-throughput sequencing and cross-linking
immunoprecipitation to identify the associated RNAs. The G3BP-complex contained
the deubiquitinating protease USP10, CtBP1 and the RNA-binding proteins Caprin-1,
G3BP2a and splicing factor proline and glutamine rich, or PSF. The G3BP-complex
binds preferentially to transcripts that retain introns, and to non-coding
sequences like 3'-untranslated region and long non-coding RNAs. Specific
transcripts with retained introns appear to be enriched in the cerebellum
compared to the rest of the brain and G3BP1 depletion decreased this intron
retention in the cerebellum of G3BP1 knockout mice. Among the enriched
transcripts, we found an overrepresentation of genes involved in synaptic
transmission, especially glutamate-related neuronal transmission. Notably, G3BP1
seems to repress the expression of the mature Grm5 (metabotropic glutamate
receptor 5) transcript, by promoting the retention of an intron in the immature
transcript in the cerebellum. Our results suggest that G3BP is involved in a new
functional mechanism to regulate non-coding RNAs including intron-retaining
transcripts, and thus have broad implications for neuronal gene regulation, where
intron retention is widespread.
PMID- 27513820
TI - Formation of Higher Silanes in Low-Temperature Silane (SiH4) Ices.
AB - A novel approach for the synthesis and identification of higher silanes
(SinH2n+2, where n <= 19) is presented. Thin films of (d4-)silane deposited onto
a cold surface were exposed under ultra-high-vacuum conditions to energetic
electrons and sampled on line and in situ via infrared and ultraviolet-visible
spectroscopy. Gas phase products released by fractional sublimation in the warm
up phase after the irradiation were probed via a reflectron time-of-flight mass
spectrometer coupled with a tunable vacuum ultraviolet photon ionization source.
The formation mechanisms of (higher) silanes were investigated by irradiating
codeposited 1:1 silane (SiH4)/d4-silane (SiD4) ices, suggesting that both radical
radical recombination and radical insertion pathways contribute to the formation
of disilane along with higher silanes up to nonadecasilane (Si19H40).
PMID- 27513821
TI - N-Acylsaccharins: Stable Electrophilic Amide-Based Acyl Transfer Reagents in Pd
Catalyzed Suzuki-Miyaura Coupling via N-C Cleavage.
AB - The development of efficient catalytic methods for N-C bond cleavage in amides
remains an important synthetic challenge. The first Pd-catalyzed Suzuki-Miyaura
cross-coupling of N-acylsaccharins with boronic acids by selective N-C bond
activation is reported. The reaction enables preparation of a variety of
functionalized diaryl and alkyl-aryl ketones with broad functional group
tolerance and in good to excellent yields. Of general interest, N-acylsaccharins
serve as new, highly reactive, bench-stable, economical, amide-based,
electrophilic acyl transfer reagents via acyl-metal intermediates. Mechanistic
studies strongly support the amide N-C(O) bond twist as the enabling feature of N
acylsaccharins in the N-C bond cleavage.
PMID- 27513822
TI - Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to
Randomized Fluid Management Strategy.
AB - RATIONALE: We previously identified two acute respiratory distress syndrome
(ARDS) subphenotypes in two separate randomized controlled trials with
differential response to positive end-expiratory pressure. OBJECTIVES: To
identify these subphenotypes in a third ARDS cohort, to test whether
subphenotypes respond differently to fluid management strategy, and to develop a
practical model for subphenotype identification. METHODS: We used latent class
analysis of baseline clinical and plasma biomarker data to identify subphenotypes
in FACTT (Fluid and Catheter Treatment Trial; n = 1,000). Logistic regression was
used to test for an interaction between subphenotype and treatment for mortality.
We used stepwise modeling to generate a model for subphenotype identification in
FACTT and validated its accuracy in the two cohorts in which we previously
identified ARDS subphenotypes. MEASUREMENTS AND MAIN RESULTS: We confirmed that a
two-class (two-subphenotype) model best described the study population.
Subphenotype 2 was again characterized by higher inflammatory biomarkers and
hypotension. Fluid management strategy had significantly different effects on 90
day mortality in the two subphenotypes (P = 0.0039 for interaction); mortality in
subphenotype 1 was 26% with fluid-conservative strategy versus 18% with fluid
liberal, whereas mortality in subphenotype 2 was 40% with fluid-conservative
strategy versus 50% in fluid-liberal. A three-variable model of IL-8,
bicarbonate, and tumor necrosis factor receptor-1 accurately classified the
subphenotypes. CONCLUSIONS: This analysis confirms the presence of two ARDS
subphenotypes that can be accurately identified with a limited number of
variables and that responded differently to randomly assigned fluid management.
These findings support the presence of ARDS subtypes that may require different
treatment approaches.
PMID- 27513823
TI - Stability-based assessment of Monteggia-type injuries predicts failure of
treatment.
AB - Paediatric Monteggia-type injuries are complicated by treatment failure and
posterior interosseous nerve palsy, without reliable predictive indicators.
Outcome is considered to be good, with little patient-reported evidence. We
propose novel radiographic parameters. A total of 33 Monteggia-type injuries were
analysed. Posterior interosseous nerve palsy was strongly predicted by the Radial
Head Displacement Index. The presence of two or more of three novel instability
markers was associated strongly with treatment failure. Patient-reported outcome
measures were almost uniformly excellent. We advocate the use of a new,
inclusive, stability-based classification of Monteggia-type injuries to predict
patients who require accurate internal fixation.
PMID- 27513824
TI - Mobile clinics for women's and children's health.
AB - BACKGROUND: The accessibility of health services is an important factor that
affects the health outcomes of populations. A mobile clinic provides a wide range
of services but in most countries the main focus is on health services for women
and children. It is anticipated that improvement of the accessibility of health
services via mobile clinics will improve women's and children's health.
OBJECTIVES: To evaluate the impact of mobile clinic services on women's and
children's health. SEARCH METHODS: For related systematic reviews, we searched
the Database of Abstracts of Reviews of Effectiveness (DARE), CRD; Health
Technology Assessment Database (HTA), CRD; NHS Economic Evaluation Database (NHS
EED), CRD (searched 20 February 2014).For primary studies, we searched ISI Web of
Science, for studies that have cited the included studies in this review
(searched 18 January 2016); WHO ICTRP, and ClinicalTrials.gov (searched 23 May
2016); Cochrane Central Register of Controlled Trials (CENTRAL), part of The
Cochrane Library. www.cochranelibrary.com (including the Cochrane Effective
Practice and Organisation of Care (EPOC) Group Specialised Register) (searched 7
April 2015); MEDLINE, OvidSP (searched 7 April 2015); Embase, OvidSP (searched 7
April 2015); CINAHL, EbscoHost (searched 7 April 2015); Global Health, OvidSP
(searched 8 April 2015); POPLINE, K4Health (searched 8 April 2015); Science
Citation Index and Social Sciences Citation Index, ISI Web of Science (searched 8
April 2015); Global Health Library, WHO (searched 8 April 2015); PAHO, VHL
(searched 8 April 2015); WHOLIS, WHO (searched 8 April 2015); LILACS, VHL
(searched 9 April 2015). SELECTION CRITERIA: We included individual- and cluster
randomised controlled trials (RCTs) and non-RCTs. We included controlled before
and-after (CBA) studies provided they had at least two intervention sites and two
control sites. Also, we included interrupted time series (ITS) studies if there
was a clearly defined point in time when the intervention occurred and at least
three data points before and three after the intervention. We defined the
intervention of a mobile clinic as a clinic vehicle with a healthcare provider
(with or without a nurse) and a driver that visited areas on a regular basis. The
participants were women (18 years or older) and children (under the age of 18
years) in low-, middle-, and high-income countries. DATA COLLECTION AND ANALYSIS:
Two review authors independently screened the titles and abstracts of studies
identified by the search strategy, extracted data from the included studies using
a specially-designed data extraction form based on the Cochrane EPOC Group data
collection checklist, and assessed full-text articles for eligibility. All
authors performed analyses, 'Risk of bias' assessments, and assessed the quality
of the evidence using the Grading of Recommendations Assessment, Development and
Evaluation (GRADE) approach. MAIN RESULTS: Two cluster-RCTs met the inclusion
criteria of this review. Both studies were conducted in the USA.One study tested
whether offering onsite mobile mammography combined with health education was
more effective at increasing breast cancer screening rates than offering health
education only, including reminders to attend a static clinic for mammography.
Women in the group offered mobile mammography and health education may be more
likely to undergo mammography within three months of the intervention than those
in the comparison group (55% versus 40%; odds ratio (OR) 1.83, 95% CI 1.22 to
2.74; low certainty evidence).A cost-effectiveness analysis of mammography at
mobile versus static units found that the total cost per patient screened may be
higher for mobile units than for static units. The incremental costs per patient
screened for a mobile over a stationary unit were USD 61 and USD 45 for a mobile
full digital unit and a mobile film unit respectively.The second study compared
asthma outcomes for children aged two to six years who received asthma care from
a mobile asthma clinic and children who received standard asthma care from the
usual (static) primary provider. Children who receive asthma care from a mobile
asthma clinic may experience little or no difference in symptom-free days, urgent
care use and caregiver-reported medication use compared to children who receive
care from their usual primary care provider. All of the evidence was of low
certainty. AUTHORS' CONCLUSIONS: The paucity of evidence and the restricted range
of contexts from which evidence is available make it difficult to draw
conclusions on the impacts of mobile clinics on women's and children's health
compared to static clinics. Further rigorous studies are needed in low-, middle-,
and high-income countries to evaluate the impacts of mobile clinics on women's
and children's health.
PMID- 27513825
TI - Transcranial magnetic stimulation for the treatment of epilepsy.
AB - BACKGROUND: Epilepsy is a highly prevalent neurological condition characterized
by repeated unprovoked seizures with various etiologies. Although antiepileptic
medications produce clinical improvement in most individuals, nearly a third of
individuals have drug-resistant epilepsy that carries significant morbidity and
mortality. There remains a need for non-invasive and more effective therapies for
this population. Transcranial magnetic stimulation (TMS) uses electromagnetic
coils to excite or inhibit neurons, with repetitive pulses at low-frequency
producing an inhibitory effect that could conceivably reduce cortical
excitability associated with epilepsy. OBJECTIVES: To assess the evidence for the
use of TMS in individuals with drug-resistant epilepsy compared with other
available treatments in reducing seizure frequency, improving quality of life,
reducing epileptiform discharges, antiepileptic medication use, and side-effects.
SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register, the
Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane
Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016),
ClinicalTrials.gov and the World Health Organization International Clinical
Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823
to June 2014) as a substitute for Embase (but it is no longer necessary to search
SCOPUS, because randomized controlled trials (RCTs) and quasi-RCTs in EMBASE are
now included in CENTRAL). SELECTION CRITERIA: Eligible studies were RCTs that
were double-blinded, single-blinded or unblinded, and placebo, no treatment, or
active controlled, which used repetitive transcranial magnetic stimulation (rTMS)
without restriction of frequency, duration, intensity, or setup (focal or vertex
treatment) on patients with drug-resistant epilepsy. The search revealed 274
records from the databases, that after selection provided seven full-text
relevant studies for inclusion. Of the seven studies included, five were
completed studies with published data and included randomized, blinded trials.
The total number of participants in the seven trials was 230. DATA COLLECTION AND
ANALYSIS: We extracted information from each trial including methodological data;
participant demographics including baseline seizure frequency, type of epileptic
drugs taken; intervention details and intervention groups for comparison;
potential biases; and outcomes and time points, primarily change in seizure
frequency or responder rates, as well as quality of life and epileptiform
discharges, adverse effects, and changes in medication use. MAIN RESULTS: Two of
the seven studies analyzed showed a statistically significant reduction in
seizure rate from baseline (72% and 78.9% reduction of seizures per week from the
baseline rate, respectively). The other five studies showed no statistically
significant difference in seizure frequency following rTMS treatment compared
with controls. We were not able to combine the results of the trials in analysis
due to differences in the designs of the studies. Four studies evaluated our
secondary endpoint of mean number of epileptic discharges, and three of the four
showed a statistically significant reduction in discharges. Quality of life was
not assessed in any of the studies. Adverse effects were uncommon among the
studies and typically involved headache, dizziness, and tinnitus. No significant
changes in medication use were found in the trials. AUTHORS' CONCLUSIONS:
Overall, we judged the quality of evidence for the primary outcomes of this
review to be low. There is evidence that rTMS is safe and not associated with any
adverse events, but given the variability in technique and outcome reporting that
prevented meta-analysis, the evidence for efficacy of rTMS for seizure reduction
is still lacking despite reasonable evidence that it is effective at reducing
epileptiform discharges.
PMID- 27513827
TI - Bicontinuous Nanoporous Frameworks: Caged Longevity for Enzymes.
AB - The preparation of bicontinuous nanoporous covalent frameworks, which are
promising for caging active enzymes, is demonstrated. The frameworks have three-
dimensionally continuous, hydrophilic pores with widths varying between 5 and 30
nm. Enzymes were infiltrated into the bicontinuous pore by applying a pressured
enzyme solution. The new materials and methods allowed the amount of caged
proteins to be controlled precisely. The resulting enzyme-loaded framework films
could be recycled many times with nearly no loss of catalytic activity. Entropic
trapping of proteins by a bicontinuous pore with the right size distribution is
an unprecedented strategy toward facile in vitro utilization of biocatalysts.
PMID- 27513828
TI - DNA Clutch Probes for Circulating Tumor DNA Analysis.
AB - Progress toward the development of minimally invasive liquid biopsies of disease
is being bolstered by breakthroughs in the analysis of circulating tumor DNA
(ctDNA): DNA released from cancer cells into the bloodstream. However, robust,
sensitive, and specific methods of detecting this emerging analyte are lacking.
ctDNA analysis has unique challenges, since it is imperative to distinguish
circulating DNA from normal cells vs mutation-bearing sequences originating from
tumors. Here we report the electrochemical detection of mutated ctDNA in samples
collected from cancer patients. By developing a strategy relying on the use of
DNA clutch probes (DCPs) that render specific sequences of ctDNA accessible, we
were able to readout the presence of mutated ctDNA. DCPs prevent reassociation of
denatured DNA strands: they make one of the two strands of a dsDNA accessible for
hybridization to a probe, and they also deactivate other closely related
sequences in solution. DCPs ensure thereby that only mutated sequences associate
with chip-based sensors detecting hybridization events. The assay exhibits
excellent sensitivity and specificity in the detection of mutated ctDNA: it
detects 1 fg/MUL of a target mutation in the presence of 100 pg/MUL of wild-type
DNA, corresponding to detecting mutations at a level of 0.01% relative to wild
type. This approach allows accurate analysis of samples collected from lung
cancer and melanoma patients. This work represents the first detection of ctDNA
without enzymatic amplification.
PMID- 27513829
TI - 8-Anilino-1-naphthalenesulfonate/Layered Double Hydroxide Ultrathin Films: Small
Anion Assembly and Its Potential Application as a Fluorescent Biosensor.
AB - The fluorescent dye 8-anilino-1-naphthalenesulfonate (ANS) is a widely used
fluorescent probe molecule for biochemistry analysis. This paper reported the
fabrication of ANS/layered double hydroxide nanosheets (ANS/LDH)n ultrathin films
(UTFs) via the layer-by-layer small anion assembly technique based on
electrostatic interaction and two possible weak interactions: hydrogen-bond and
induced electrostatic interactions between ANS and positive-charged LDH
nanosheets. The obtained UTFs show a long-range-ordered periodic layered stacking
structure and weak fluorescence in dry air or water, but it split into three
narrow strong peaks in a weak polarity environment induced by the two-dimensional
(2D) confinement effect of the LDH laminate; the fluorescence intensity increases
with decreasing the solvent polarity, concomitant with the blue shift of the
emission peaks, which show good sensoring reversibility. Meanwhile, the UTFs
exhibit selective fluorescence enhancement to the bovine serum albumin (BSA)-like
protein biomolecules, and the rate of fluorescence enhancement with the protein
concentration is significantly different with the different protein aggregate
states. The (ANS/LDH)n UTF has the potential to be a novel type of biological
flourescence sensor material.
PMID- 27513832
TI - Structural diversity of halocarbonyl molybdenum and tungsten PNP pincer complexes
through ligand modifications.
AB - This work presents a comparative study of a series of halocarbonyl Mo(ii) and
W(ii) complexes of the types [M(PNP)(CO)3X]X and [M(PNP)(CO)2X2] (M = Mo, W; X =
I, Br), featuring PNP pincer ligands based on a 2,6-diaminopyridine scaffold. The
complexes were prepared and fully characterized. The syntheses of these complexes
were accomplished by treatment of [M(PNP)(CO)3] with stoichiometric amounts of I2
and Br2, respectively. The modification of the 2,6-diaminopyridine scaffold by
introducing NMe and NPh instead of NH spacers with concomitant modification of
the phosphine moieties changed the steric and electronic properties of the PNP
ligand significantly. While in the case of NH linkers exclusively cationic seven
coordinate complexes of the type [M(PNP)(CO)3X](+) were obtained with NMe and NPh
spacers neutral seven-coordinate complexes of the type [M(PNP)(CO)2X2] were
afforded. In the case of the latter, when the reaction is performed in the
presence of CO also [M(PNP)(CO)3X](+) complexes are formed which slowly lose CO
to give [M(PNP)(CO)2X2]. The halocarbonyl tungsten chemistry parallels that of
molybdenum. The only exception is molybdenum in conjunction with the PNP(Me)-iPr
ligand, where the coordinatively unsaturated complex [Mo(PNP(Me)-iPr)(CO)X2] is
formed. DFT mechanistic studies reveal that the seven-coordinate complexes should
be the thermodynamic as well as the kinetic products. Since [Mo(PNP(Me)
iPr)(CO)X2] is the observed product it suggests that the reaction follows an
alternative path. Structures of representative complexes were determined by X-ray
single crystal analyses.
PMID- 27513830
TI - Phenotypic evolution of UNC80 loss of function.
AB - Failure to thrive arises as a complication of a heterogeneous group of disorders.
We describe two female siblings with spastic paraplegia and global developmental
delay but also, atypically for the HSPs, poor weight gain classified as failure
to thrive. After extensive clinical and biochemical investigations failed to
identify the etiology, we used exome sequencing to identify biallelic UNC80
mutations (NM_032504.1:c.[3983-3_3994delinsA];[2431C>T]. The paternally inherited
NM_032504.1:c.3983-3_3994delinsA is predicted to encode p.Ser1328Argfs*19 and the
maternally inherited NM_032504.1:c.2431C>T is predicted to encode p.Arg811*. No
UNC80 mRNA was detectable in patient cultured skin fibroblasts, suggesting UNC80
loss of function by nonsense mediated mRNA decay. Further supporting the UNC80
mutations as causative of these siblings' disorder, biallelic mutations in UNC80
have recently been described among individuals with an overlapping phenotype.
This report expands the disease spectrum associated with UNC80 mutations. (c)
2016 Wiley Periodicals, Inc.
PMID- 27513834
TI - Alopecia areata in patients with inflammatory bowel disease: an overview.
AB - Alopecia areata (AA) is one of the most common causes of non-scarring hair loss,
which is associated with the premature induction of hair follicle regression. The
pathogenesis of AA is unknown, although it is believed that a complicated
autoimmune mechanism with Th1 lymphocytes and proinfammatory cytokines, such as
IFN-gamma, TNF-alpha, IL-1 and IL-2, may be involved. AA may occur as a single
disease entity or coexist with other autoimmunological disorders. In some cases
the relationship with infammatory bowel disease (IBD) was observed and the link
between molecular pathways and main proinfammatory cytokines in IBD and AA has
been suggested. AA is also described in literature as a side efect of biological
therapy with the anti-TNF-alpha agents. To address the association between AA and
IBD, in this review we discuss the most relevant clinical studies and case
reports found in MEDLINE, Pubmed and EMBASE.
PMID- 27513835
TI - Urine NGAL is useful in the clinical evaluation of renal function in the early
course of acute pancreatitis.
AB - INTRODUCTION: Acute Kidney Injury (AKI) is a serious early complications in
patients with acute pancreatitis (AP) that signifcantly increases mortality rates
compared to patients without AKI. The early diagnosis of AKI during its treatable
phases and implementation of appropriate treatment protocols can improve outcomes
for this group of patients. A promising biomarker for AKI is neutrophil
gelatinase-associated lipocalin (NGAL). AIM: This study evaluated the diagnostic
value of NGAL concentrations in serum and in urine for patients developing AKI as
an early complication of AP compared to AP patients without AKI. MATERIAL AND
METHODS: The study group composed of 65 patients (34 men and 31 women) with a
mean age of 62.2 +/- 16 years with AP and hospitalized in the Surgery Department
of the Direct Hospital in Sucha Beskidzka, Poland between January and December
2014. Serum NGAL (sNGAL) levels were measured with the BioVendor ELISA kit, and
urine NGAL (uNGAL) with the Abbott ARCHITECT Analyzer. RESULTS: In the early
phase of AP, 11 patients (17%) developed AKI, including 10 patients with stage 1
and one with stage 2. AKI was associated with more severe AP, higher BISAP
scores, the need for more intensive treatment, longer hospital stays and higher
mortality. Both serum and urine NGAL concentrations were signifcantly higher in
patients with AKI throughout the study and signifcantly predicted AKI in simple
and multiple logistic regression adjusted for age, sex and comorbidities. Serum
and urine NGAL concentrations were signifcantly correlated with levels of serum
urea, creatinine, urine albumin, and the maximum change in serum creatinine.
Serum and urine NGAL levels also correlated positively with direct neutrophil
counts and CRP concentrations throughout the study. CONCLUSIONS: The measurement
of NGAL levels, particularly in urine, is simple, easy to interpret, routinely
available, and clinically useful in the assessment of dynamic changes in kidney
function for patients with AP.
PMID- 27513836
TI - Vascular density, angiogenesis and pro-angiogenic factors in uterine fibroids.
AB - Angiogenesis is a process of development of new vessels from the preexisting
vascular network of a host. This is process which is seen in many physiological
situations but it accompanies also a development of different lesions, i.e.
neoplasms. Uterine fibroids are one of the most frequent lesions which affect
human internal female genital tracts. Authors briefly review most important pro
angiogenic factors, based on their own observation as well as reviewing current
literature. They pay much attention to vascular density which is significantly
changed in the uterine tumors.
PMID- 27513837
TI - Blood vessels of the shin - anterior tibial artery - anatomy and embryology - own
studies and review of the literature.
AB - Injuries of the lower leg are rather frequent in every day orthopedic routine.
Process of healing takes quite a long time and is commonly dependent on the
proper vasculature. e study was carried out on 50 human lower legs obtained
during autopsies. The anatomy of the vascular system of the leg was studied using
classical anatomical dissection methods. Based also on literature we have
reviewed the current knowledge on the vascularization of the lower leg and its
embryological background.
PMID- 27513838
TI - Experimental gender related obesity effect of diet.
AB - INTRODUCTION: High-calorie diet is responsible for excessive weight gain. Obesity
has recently become world epidemics, affecting not only adults but also children,
which makes it the biggest health problem in the world. Yet the underlying
mechanism remains a matter of debate. OBJECTIVES: The aim of this study is to
clarify the role of gender in high fat diet induced obesity in pups and adult
animals. MATERIALS AND METHODS: Female rats were fed low/ high fat diet during
mating, pregnancy and lactation. The offspring and adult rats fed different diet
had their body weight and temperature measurements taken twice a week. On the
21st day of the experiment the animals underwent anesthesia in order to have
their blood samples collected for lipid profile. RESULTS: After 3 weeks on HF
diet female pups body weight was higher than in control group (p <0.05). Contrary
to the female pups, the increase in body weight was higher (p <0.05) in male pups
and occurred after 2 and 3 weeks. In adult female rats body weight increased
after 2 weeks on HF, while in adult male group such weight gain was observed no
sooner than after 3 weeks. A er three weeks of the experiment body weight was
correlated positively (r = 0.941) with lipid profile of adult both gender groups
on HF diet. CONCLUSIONS: In male pups group body weight increased faster and
achieved higher values then in female pups. On the contrary, in adult group of
females body weight increased faster than in male rats and achieved similar
values.
PMID- 27513839
TI - Terapeutic importance of apoptosis pathways in pancreatic cancer.
AB - Recent studies indicate the significant role of apoptosis and the genes that
control it in the process of carcinogenesis. Apoptosis or programmed cell death
is a complex process that controls cell proliferation and maintenance of
accounting for the necessary balance in the body. Disturbances of apoptotic
signalling pathways directly lead to the development and progression of cancer.
This also applies to pancreatic cancer, which is characterized by poor prognosis
and resistance to treatment. In recent years progress has been made concerning
the complex pathways of apoptosis, which allowed the development of new
therapeutic strategies. This article reviews current knowledge on apoptosis
pathways and their role in treatment of pancreatic cancer.
PMID- 27513840
TI - Morphology, topography and clinical signi cance of the jugular foramen.
AB - The paper describes morphological variants of the jugular foramen of the human
skull and discusses the reasons for its frequent asymmetry. Bilateral
disproportions between the anteroposterior and mediolateral diameters of the
jugular foramina were analyzed. We established that the jugular foramen is
extremely narrow when its anteroposterior diameter is less than 5.0 mm. When the
mediolateral diameter exceeds 20.0 mm, then the foramen exhibits extreme
widening.
PMID- 27513841
TI - The effect of peripheral chronic salsolinol administration on fat pad adipocytes
morphological parameters.
AB - Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to
regulate dopaminergic neurons and to act as a mediator in the neuroendocrine
system. We have previously reported that exogenous salsolinol evokes enteric
neuronal cell death, leading to the impairment of myenteric neurons density and
abnormal intestinal transit in rats. We also observed significant reduction of
body weight, related to the disrupted gastrointestinal homeostasis. e aim of
current study was to evaluate the influence of prolonged salsolinol
administration body weight, food intake, adipose tissue accumulation and fad pad
adipocyte morphological parameters assessed by image analysis. Male Wistar rats
were subjected to continuous intraperitoneal low dosing of salsolinol - 200 mg/kg
in total with ALZET osmotic mini-pumps (Durtec, USA) for 2 or 4 weeks with either
normal or high-fat diet. Appropriate groups served as the controls. Food intake,
body weight were measured each morning. Both epididymal fat pads were dissected,
weighted and processed for routine hematoxylin and eosin staining. e following
parameters: cell area, perimeter, long and short axis, aspect ratio and
circularity factor were assessed in stained specimens with the image analysis
system (Multiscan, Poland). Salsolinol administration significantly reduced total
body mass with no differences in total food intake between the groups. The
epididymal fat pad weight over final body mass ratio was lower in salsolinol
treated rats on high fat diet in comparison with the control groups. e area,
perimeter, short and long axis of the fad pad adipocytes were significantly
decreased in salsolinol treated animals in comparison with relevant controls.
Salsolinol targets some regulatory mechanisms concerned with the basic rat
metabolism. Prolonged peripheral salsolinol administration in rats significantly
decreases the adipocyte size, and such effect is related to the weight loss and
reduced adipose tissue accumulation.
PMID- 27513842
TI - Is It Necessary To Place Prophylactically an Abdominal Drain To Prevent Surgical
Site Infection in Abdominal Operations? A Systematic Meta-Review.
AB - BACKGROUND: There is still uncertainty regarding the use of prophylactic drainage
in abdominal surgical procedures. This meta-review aimed to summarize systematic
reviews and meta-analyses evaluating abdominal drain placement in patients
undergoing abdominal procedures, with a focus on surgical site infection and
death from infections. METHODS: Systematic reviews and meta-analyses identified
in MEDLINE, EMBASE, CINHAL, Cochrane Central Register of Controlled Trials, World
Health Organization Regional Medical Databases, and African Index Medicus were
reviewed. RESULTS: Fifteen systematic reviews and meta-analyses concerning
prophylactic abdominal drainage in abdominal operations were included in this
analysis. The median score of methodologic quality was eight (6-10). The majority
of meta-analyses found no benefits of prophylactic drainage in reducing surgical
site infection, but no significant differences were identified. Three studies
demonstrated a significant difference in favor of no drainage, with two regarding
cholecystectomy and one on appendectomy (p < 0.05). The quality of evidence
provided by each review was mainly low and very low. CONCLUSIONS: Most reviews
fail to detect an increased incidence of surgical site infection in the setting
of drainage placement but also fail to attribute any specific benefits to the
presence of a drain in abdominal procedures.
PMID- 27513843
TI - Sexual Identity, Sex of Sexual Contacts, and Health-Related Behaviors Among
Students in Grades 9-12 - United States and Selected Sites, 2015.
AB - PROBLEM: Sexual identity and sex of sexual contacts can both be used to identify
sexual minority youth. Significant health disparities exist between sexual
minority and nonsexual minority youth. However, not enough is known about health
related behaviors that contribute to negative health outcomes among sexual
minority youth and how the prevalence of these health-related behaviors compare
with the prevalence of health-related behaviors among nonsexual minorities.
REPORTING PERIOD: September 2014-December 2015. DESCRIPTION OF THE SYSTEM: The
Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of
priority health-related behaviors among youth and young adults: 1) behaviors that
contribute to unintentional injuries and violence; 2) tobacco use; 3) alcohol and
other drug use; 4) sexual behaviors related to unintended pregnancy and sexually
transmitted infections, including human immunodeficiency virus infection; 5)
unhealthy dietary behaviors; and 6) physical inactivity. In addition, YRBSS
monitors the prevalence of obesity and asthma and other priority health-related
behaviors. YRBSS includes a national school-based Youth Risk Behavior Survey
(YRBS) conducted by CDC and state and large urban school district school-based
YRBSs conducted by state and local education and health agencies. For the 2015
YRBSS cycle, a question to ascertain sexual identity and a question to ascertain
sex of sexual contacts was added for the first time to the national YRBS
questionnaire and to the standard YRBS questionnaire used by the states and large
urban school districts as a starting point for their YRBS questionnaires. This
report summarizes results for 118 health-related behaviors plus obesity,
overweight, and asthma by sexual identity and sex of sexual contacts from the
2015 national survey, 25 state surveys, and 19 large urban school district
surveys conducted among students in grades 9-12. RESULTS: Across the 18 violence
related risk behaviors nationwide, the prevalence of 16 was higher among gay,
lesbian, and bisexual students than heterosexual students and the prevalence of
15 was higher among students who had sexual contact with only the same sex or
with both sexes than students who had sexual contact with only the opposite sex.
Across the 13 tobacco use-related risk behaviors, the prevalence of 11 was higher
among gay, lesbian, and bisexual students than heterosexual students and the
prevalence of 10 was higher among students who had sexual contact with only the
same sex or with both sexes than students who had sexual contact with only the
opposite sex. Similarly, across the 19 alcohol or other drug use-related risk
behaviors, the prevalence of 18 was higher among gay, lesbian, and bisexual
students than heterosexual students and the prevalence of 17 was higher among
students who had sexual contact with only the same sex or with both sexes than
students who had sexual contact with only the opposite sex. This pattern also was
evident across the six sexual risk behaviors. The prevalence of five of these
behaviors was higher among gay, lesbian, and bisexual students than heterosexual
students and the prevalence of four was higher among students who had sexual
contact with only the same sex or with both sexes than students who had sexual
contact with only the opposite sex. No clear pattern of differences emerged for
birth control use, dietary behaviors, and physical activity. INTERPRETATION: The
majority of sexual minority students cope with the transition from childhood
through adolescence to adulthood successfully and become healthy and productive
adults. However, this report documents that sexual minority students have a
higher prevalence of many health-risk behaviors compared with nonsexual minority
students. PUBLIC HEALTH ACTION: To reduce the disparities in health-risk
behaviors among sexual minority students, it is important to raise awareness of
the problem; facilitate access to education, health care, and evidence-based
interventions designed to address priority health-risk behaviors among sexual
minority youth; and continue to implement YRBSS at the national, state, and large
urban school district levels to document and monitor the effect of broad policy
and programmatic interventions on the health-related behaviors of sexual minority
youth.
PMID- 27513844
TI - AMPK Mediates Glucocorticoids Stress-Induced Downregulation of the Glucocorticoid
Receptor in Cultured Rat Prefrontal Cortical Astrocytes.
AB - Chronic stress induces altered energy metabolism and plays important roles in the
etiology of depression, in which the glucocorticoid negative feedback is
disrupted due to imbalanced glucocorticoid receptor (GR) functions. The mechanism
underlying the dysregulation of GR by chronic stress remains elusive. In this
study, we investigated the role of AMP-activated protein kinase (AMPK), the key
enzyme regulating cellular energy metabolism, and related signaling pathways in
chronic stress-induced GR dysregulation. In cultured rat cortical astrocytes,
glucocorticoid treatment decreased the level, which was accompanied by the
decreased expression of liver kinase B1 (LKB1) and reduced phosphorylation of
AMPK. Glucocorticoid-induced effects were attenuated by glucocorticoid-inducible
kinase 1 (SGK1) inhibitor GSK650394, which also inhibited glucocorticoid induced
phosphorylation of Forkhead box O3a (FOXO3a). Furthermore, glucocorticoid-induced
down-regulation of GR was mimicked by the inhibition of AMPK and abolished by the
AMPK activators or the histone deacetylase 5 (HDAC5) inhibitors. In line with the
role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid
induced reduction of AMPK phosphorylation and GR expression as well as behavioral
alteration of rats. Taken together, these results suggest that chronic stress
activates SGK1 and suppresses the expression of LKB1 via inhibitory
phosphorylation of FOXO3a. Downregulated LKB1 contributes to reduced activation
of AMPK, leading to the dephosphorylation of HDAC5 and the suppression of
transcription of GR.
PMID- 27513846
TI - Action Sport Cameras as an Instrument to Perform a 3D Underwater Motion Analysis.
AB - Action sport cameras (ASC) are currently adopted mainly for entertainment
purposes but their uninterrupted technical improvements, in correspondence of
cost decreases, are going to disclose them for three-dimensional (3D) motion
analysis in sport gesture study and athletic performance evaluation
quantitatively. Extending this technology to sport analysis however still
requires a methodologic step-forward to making ASC a metric system, encompassing
ad-hoc camera setup, image processing, feature tracking, calibration and 3D
reconstruction. Despite traditional laboratory analysis, such requirements become
an issue when coping with both indoor and outdoor motion acquisitions of
athletes. In swimming analysis for example, the camera setup and the calibration
protocol are particularly demanding since land and underwater cameras are
mandatory. In particular, the underwater camera calibration can be an issue
affecting the reconstruction accuracy. In this paper, the aim is to evaluate the
feasibility of ASC for 3D underwater analysis by focusing on camera setup and
data acquisition protocols. Two GoPro Hero3+ Black (frequency: 60Hz; image
resolutions: 1280*720/1920*1080 pixels) were located underwater into a swimming
pool, surveying a working volume of about 6m3. A two-step custom calibration
procedure, consisting in the acquisition of one static triad and one moving wand,
carrying nine and one spherical passive markers, respectively, was implemented.
After assessing camera parameters, a rigid bar, carrying two markers at known
distance, was acquired in several positions within the working volume. The
average error upon the reconstructed inter-marker distances was less than 2.5mm
(1280*720) and 1.5mm (1920*1080). The results of this study demonstrate that the
calibration of underwater ASC is feasible enabling quantitative kinematic
measurements with accuracy comparable to traditional motion capture systems.
PMID- 27513847
TI - Coordination of deep hip muscle activity is altered in symptomatic
femoroacetabular impingement.
AB - Diagnosis of femoroacetabular impingement (FAI) is increasing, yet the associated
physical impairments remain poorly defined. This morphological hip condition can
cause joint pain, stiffness, impaired function, and eventually hip
osteoarthritis. This exploratory study compared coordination of deep hip muscles
between people with and without symptomatic FAI using analysis of muscle
synergies (i.e., patterns of activity of groups of muscles activated in
synchrony) during gait. Fifteen individuals (11 males) with symptomatic FAI
(clinical examination and imaging) and 14 age- and sex-comparable controls
without morphological FAI underwent testing. Intramuscular fine-wire and surface
electrodes recorded electromyographic activity of selected deep and superficial
hip muscles. A non-negative matrix factorization algorithm extracted three
synergies which were compared between groups. Information regarding which muscles
were activated together in the FAI group (FAI group synergy vector) was used to
reconstruct individual electromyography patterns and compare groups. Variance
accounted for (VAF) by three synergies was less for the control (94.8 [1.4]%)
than FAI (96.0 [1.0]%) group (p = 0.03). VAF of obturator internus was
significantly higher in the FAI group (p = 0.02). VAF of the reconstructed
individual electromyography patterns with the FAI or control group vector were
significantly higher for the FAI group (p < 0.01). Following reconstruction, VAF
of quadratus femoris was significantly more reduced in controls (p = 0.04),
indicating greater between-subject variability. Coordination of deep hip muscles
in the synergy related to hip joint control during early swing differed between
groups. This phase involves movement towards the impingement position, which has
relevance for the interpretation of synergy differences and potential clinical
importance. (c) 2016 Orthopaedic Research Society. Published by Wiley
Periodicals, Inc. J Orthop Res 35:1494-1504, 2017.
PMID- 27513848
TI - Extent of Signal Hyperintensity on Unenhanced T1-weighted Brain MR Images after
More than 35 Administrations of Linear Gadolinium-based Contrast Agents.
AB - Purpose To explore the extent of signal hyperintensity in the brain on unenhanced
T1-weighted magnetic resonance (MR) images with increasing gadolinium-based
contrast agent (GBCA) doses in patients who received 35 or more linear GBCA
administrations. Materials and Methods In this institutional review board
approved HIPAA-compliant retrospective study, picture archiving and communication
systems of two tertiary referral hospitals were searched to identify patients who
received 35 or more linear GBCA administrations. Unenhanced T1-weighted images of
the brain in patients after six, 12, and 24 GBCA administrations and after the
final GBCA administration were independently reviewed by three radiologists to
identify sites where T1 signal intensity was increasing. Areas identified by all
three observers as increasing in T1 signal intensity when compared with baseline
images were further analyzed with a quantitative region of interest analysis
measuring the rate of signal increase per injection and the total change after 24
linear GBCA administrations relative to reference tissues that did not show T1
shortening. Results Qualitative analysis of 13 patients with 39-59 linear GBCA
administrations showed visually detectable T1 shortening in the dentate nucleus
(n = 13), globus pallidus (n = 13), substantia nigra (n = 13), posterior thalamus
(n = 12), red nucleus (n = 10), colliculi (n = 10), superior cerebellar peduncle
(n = 7), caudate nucleus (n = 4), whole thalamus (n = 3), and putamen (n = 2).
Quantitative analysis enable confirmation of signal intensity increases on
unenhanced T1-weighted images relative to reference tissues in the dentate
nucleus (0.53% signal intensity increase per injection, P < .001), globus
pallidus (0.23% increase, P = .009), posterior thalamus (0.26% increase, P <
.001), substantia nigra (0.25% increase, P = .01), red nucleus (0.25% increase, P
= .01), cerebellar peduncle (0.19% increase, P = .001), and colliculi (0.21%
increase, P = .02). Conclusion Increased signal intensity on unenhanced T1
weighted images was seen in the posterior thalamus, substantia nigra, red
nucleus, cerebellar peduncle, colliculi, dentate nucleus, and globus pallidus.
(c) RSNA, 2016.
PMID- 27513849
TI - 18F Fluorocholine Dynamic Time-of-Flight PET/MR Imaging in Patients with Newly
Diagnosed Intermediate- to High-Risk Prostate Cancer: Initial Clinical-Pathologic
Comparisons.
AB - Purpose To investigate the initial clinical value of fluorine 18 (18F)
fluorocholine (FCH) dynamic positron emission tomography (PET)/magnetic resonance
(MR) imaging by comparing its parameters with clinical-pathologic findings in
patients with newly diagnosed intermediate- to high-risk prostate cancer (PCa)
who plan to undergo radical prostatectomy. Materials and Methods The
institutional review board approved the study protocol, and informed written
consent was obtained from all subjects for this HIPAA-compliant study. Twelve men
(mean age +/- standard deviation, 61.7 years +/- 8.4; range, 46-74 years) with
untreated intermediate- to high-risk PCa characterized according to Cancer of the
Prostate Risk Assessment (CAPRA) underwent preoperative FCH dynamic PET/MR
imaging followed by radical prostatectomy between April and November 2015. PET/MR
imaging parameters including average and maximum K1 (delivery rate constant) and
standardized uptake values (SUVs) and Prostate Imaging Reporting and Data System
(PI-RADS) version 2 scores were measured and compared with clinical-pathologic
characteristics. For statistical analysis, the Spearman rank correlation and Mann
Whitney U tests were performed. Results Of the PET parameters, maximum SUV of
primary tumors showed significant correlations with several clinical-pathologic
parameters including serum prostate-specific antigen level (rho = 0.71, P = .01),
pathologic stage (rho = 0.59, P = .043), and postsurgical CAPRA score (rho =
0.72, P = .008). The overall PI-RADS score showed significant correlations with
pathologic tumor volume (rho = 0.81, P < .001), percentage of tumor cells with
Gleason scores greater than 3 (rho = 0.59, P = .02), and postsurgical CAPRA score
(rho = 0.58, P = .046). The high-risk postsurgical CAPRA score patient group had
a significantly higher maximum SUV than did the intermediate-risk group. Combined
PET and MR imaging showed improved sensitivity (88%) for prediction of pathologic
extraprostatic extension compared with that with MR imaging (50%) and PET (75%)
performed separately. Conclusion Maximum SUVs and PI-RADS scores from FCH PET/MR
imaging show good correlation with clinical-pathologic characteristics, such as
postsurgical CAPRA score, which are related to prognosis in patients with newly
diagnosed intermediate- to high-risk PCa. (c) RSNA, 2016 Online supplemental
material is available for this article.
PMID- 27513850
TI - Detection of Steatohepatitis in a Rat Model by Using Spectroscopic Shear-Wave US
Elastography.
AB - Purpose To compare low- versus high-frequency ultrasonographic (US) elastography
for detection of steatohepatitis in rats by using histopathologic findings as the
reference standard. Materials and Methods Between March and September 2014, after
receiving approval from the institutional animal care committee, 60 male Sprague
Dawley rats were fed either a standard chow for 4 weeks or a methionine- and
choline-deficient diet for 1, 4, 8, or 12 weeks to induce a continuum of
steatohepatitis severity. Liver shear stiffness was assessed in vivo by using US
elastography at low (40-130-Hz) and high (130-220-Hz) frequencies. Histologic
features (steatosis, inflammation, and fibrosis) and modified nonalcoholic
steatohepatitis categories were used as reference standards. Definite
steatohepatitis was divided into steatohepatitis with fibrosis stage 1 or lower
and stage 2 and higher. Analyses included the Kendall tau correlation,
multivariable linear regression analyses, Kruskal-Wallis rank sum test, and post
hoc Dunn test with Holm correction. Results Correlations between liver shear
stiffness and histologic features were higher at high frequencies than at low
frequencies (low frequency: 0.08, 0.24, and 0.20 for steatosis, inflammation, and
fibrosis, respectively; high frequency: 0.11, 0.35, and 0.50, respectively). The
absolute value of multivariable regression coefficients was higher at high
frequencies for the presence of steatosis, inflammation grade, and fibrosis stage
(low frequency: -0.475, 0.157, and 0.209, respectively; high frequency: -0.893,
0.357, and 0.447, respectively). The model fit was better at high frequencies
(adjusted R2 = 0.57) than at low frequencies (adjusted R2 = 0.21). There was a
significant difference between steatohepatitis categories at both low and high
frequencies (P = .022 and P < .001, respectively). Conclusion Liver shear
stiffness measured with US elastography provided better distinction of
steatohepatitis categories at high frequencies than at low frequencies. Further,
liver shear stiffness decreased with steatosis and increased with inflammation
and fibrosis at both low and high frequencies. (c) RSNA, 2016 Online supplemental
material is available for this article.
PMID- 27513851
TI - Predicting Ligand Binding Sites on Protein Surfaces by 3-Dimensional Probability
Density Distributions of Interacting Atoms.
AB - Predicting ligand binding sites (LBSs) on protein structures, which are obtained
either from experimental or computational methods, is a useful first step in
functional annotation or structure-based drug design for the protein structures.
In this work, the structure-based machine learning algorithm ISMBLab-LIG was
developed to predict LBSs on protein surfaces with input attributes derived from
the three-dimensional probability density maps of interacting atoms, which were
reconstructed on the query protein surfaces and were relatively insensitive to
local conformational variations of the tentative ligand binding sites. The
prediction accuracy of the ISMBLab-LIG predictors is comparable to that of the
best LBS predictors benchmarked on several well-established testing datasets.
More importantly, the ISMBLab-LIG algorithm has substantial tolerance to the
prediction uncertainties of computationally derived protein structure models. As
such, the method is particularly useful for predicting LBSs not only on
experimental protein structures without known LBS templates in the database but
also on computationally predicted model protein structures with structural
uncertainties in the tentative ligand binding sites.
PMID- 27513852
TI - Meeting Report: Translational Considerations of Novel Vector Management
Approaches.
PMID- 27513853
TI - The Relationship between Gray Matter Quantitative MRI and Disability in Secondary
Progressive Multiple Sclerosis.
AB - PURPOSE: In secondary progressive Multiple Sclerosis (SPMS), global
neurodegeneration as a driver of disability gains importance in comparison to
focal inflammatory processes. However, clinical MRI does not visualize changes of
tissue composition outside MS lesions. This quantitative MRI (qMRI) study
investigated cortical and deep gray matter (GM) proton density (PD) values and T1
relaxation times to explore their potential to assess neuronal damage and its
relationship to clinical disability in SPMS. MATERIALS AND METHODS: 11 SPMS
patients underwent quantitative T1 and PD mapping. Parameter values across the
cerebral cortex and deep GM structures were compared with 11 healthy controls,
and correlation with disability was investigated for regions exhibiting
significant group differences. RESULTS: PD was increased in the whole GM,
cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in
the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was
prolonged and correlated with disability in the whole GM and cerebral cortex.
CONCLUSION: Our study suggests that the qMRI parameters GM PD (which likely
indicates replacement of neural tissue with water) and cortical T1 (which
reflects cortical damage including and beyond increased water content) are
promising qMRI candidates for the assessment of disease status, and are related
to disability in SPMS.
PMID- 27513854
TI - Effect of Obesity on Acute Ozone-Induced Changes in Airway Function, Reactivity,
and Inflammation in Adult Females.
AB - We previously observed greater ozone-induced lung function decrements in obese
than non-obese women. Animal models suggest that obesity enhances ozone-induced
airway reactivity and inflammation. In a controlled exposure study, we compared
the acute effect of randomized 0.4ppm ozone and air exposures (2 h with
intermittent light exercise) in obese (N = 20) (300.05). In addition, after induced differentiation,
the lipid droplet production significantly decreased, and the percentages of
methylation in the promoter regions of C/EBPalpha, PPARgamma, and aP2 genes were
0.9%, 80%, and 76%, respectively. In contrast, the percentages of methylation in
the negative control groups were 0.5%, 67.5%, and 58%, respectively. CONCLUSION:
TDG gene knockdown could inhibit the differentiation of pig preadipocytes and
affect the DNA methylation levels of some transcription factors.
PMID- 27513858
TI - Changes in Knee Laxity and Relaxin Receptor Isoforms Expression (RXFP1/RXFP2) in
the Knee throughout Estrous Cycle Phases in Rodents.
AB - The changes in knee laxity and relaxin receptor expression at different phases of
rodent estrous cycle are not known. Here, changes in the parameter were
investigated in rats at different phases of the estrous cycle. Estrous cycle
phases of intact female rats were determined by cytological examination of the
vaginal smear. Following phase identification, blood was collected for serum
hormone analyses. Knee passive range of motion (ROM) was determined by using a
digital miniature goniometer. The animals were then sacrificed and patellar
tendon, collateral ligaments and hamstring muscles were harvested for
relaxin/insulin-like family peptide receptor 1 and 2 (RXFP1/RXFP2) analyses. Knee
passive ROM was the highest at proestrus followed by diestrus and the lowest at
estrus. Estrogen level was the highest at proestrus while progesterone and
relaxin levels were the highest at diestrus. A strong correlation was observed
between relaxin and progesterone levels. At proestrus, expression of RXFP1 and
RXFP2 proteins and mRNAs were the highest at proestrus followed by diestrus and
estrus. The finding shows that higher level of progesterone and relaxin in
diestrus might be responsible for higher laxity of knee joint in rats.
PMID- 27513859
TI - The Motivational Salience of Faces Is Related to Both Their Valence and
Dominance.
AB - Both behavioral and neural measures of the motivational salience of faces are
positively correlated with their physical attractiveness. Whether physical
characteristics other than attractiveness contribute to the motivational salience
of faces is not known, however. Research with male macaques recently showed that
more dominant macaques' faces hold greater motivational salience. Here we
investigated whether dominance also contributes to the motivational salience of
faces in human participants. Principal component analysis of third-party ratings
of faces for multiple traits revealed two orthogonal components. The first
component ("valence") was highly correlated with rated trustworthiness and
attractiveness. The second component ("dominance") was highly correlated with
rated dominance and aggressiveness. Importantly, both components were positively
and independently related to the motivational salience of faces, as assessed from
responses on a standard key-press task. These results show that at least two
dissociable components underpin the motivational salience of faces in humans and
present new evidence for similarities in how humans and non-human primates
respond to facial cues of dominance.
PMID- 27513860
TI - Quality of Care Is Improved by Rapid Short Incubation MALDI-ToF Identification
from Blood Cultures as Measured by Reduced Length of Stay and Patient Outcomes as
Part of a Multi-Disciplinary Approach to Bacteremia in Pediatric Patients.
AB - Sepsis has seen an incremental increase in cases of about 13% annually in the USA
and accounts for approximately 4400 deaths among pediatric patients. Early
identification of the specific pathogen allows the clinician to ensure that the
antibiotic coverage is optimal, an intervention that has been shown to improve
patient outcomes in sepsis. Our study's objective was to assess the impact of a
rapid Bruker MALDI-Tof identification protocol on pediatric sepsis cases by
assessing various indicators. We assessed the quality of care by measuring the
following indicators; time to identification of the pathogen, initiation of the
most appropriate antibiotic, length of stay (LOS) in hospital and patient
outcomes, using a retrospective review over three consecutive years. In total 92
pediatric patients, similar in age and gender distributions were assessed; 37 in
2012, 33 in 2013 and 22 in 2014. The introduction of MALDI-TOF identification in
2013 led to a significant decrease in time to identify a pathogen by 21.03 hours
(p = 1.95E-05). A short incubation MALDI-TOF identification protocol in 2014
further reduced time to identification by 17.75 hours (p = 2.48E-3). Overall in
2014 this led to a trend to earlier optimization of antibiotics by 20.2 hours (p
= 0.14) and a reduction in length of stay after the implementation of MALDI-ToF
identification in 2013 of 3.07 days and a further reduction of 8.92 days after
the introduction of the rapid short incubation identification protocol using
MALDI-Tof in 2014 (P = 0.12). By evaluating the subgroup of patients where
antibiotics were changed, our study confirmed that patients received appropriate
therapy 48.8% (20.2 hours) earlier compared to conventional methods leading to a
decrease in length of stay of 23.65 days after the implementation of MALDI-ToF
identification and a further reduction of 9.82 days in 2014 compared to 2012 (p =
0.02). In 2014 outcomes between the patients needing a change in their antibiotic
compared to the patients where the empirical therapy was considered to be optimal
were similar with respect to length of stay; 13.04 and 10.93 days (p = 0.34). In
the 2012 group there was a significant increase in the length of stay in the
group needing change in excess of 30 days (p = 0.02) compared to the group where
empirical therapy was considered to be optimal, this clearly showed an
improvement in the quality of care received after the rapid identification was
instituted in 2014. The 2012 group had a four times overall increased sepsis
associated mortality risk compared to the 2014 group and when empirical
antibiotics needed to be optimized this risk was 7 times compared to the 2014
group. We conclude that rapid identification of bacterial pathogens in pediatric
blood cultures with a rapid incubation MALDI-TOF identification protocol plays an
important role in improving quality of care as part of a multidisciplinary
approach to pediatric bacteremia and sepsis.
PMID- 27513862
TI - Ingenol Mebutate 500 MUg for Treatment of the Scalp in Refractory Field
Cancerization.
AB - Patients suffering from chronic lymphocytic leukemia often develop actinic
keratosis (AK) and squamous cell carcinoma in sun-exposed areas. In these
particular patients, who have a suboptimal immune function, AK treatment can be
particularly challenging. We report the case of a patient who failed to respond
to most AK treatments, including 5-FU, imiquimod and photodynamic therapy, but
responded to ingenol mebutate. We started with 3 applications of 150 MUg/g
(registered treatment of the scalp) and also 2 applications of 500 MUg/g
(registered in for trunk and extremities). Both treatments were well tolerated,
but only the latter led to significant clinical success. This suggests that 500
MUg/g of ingenol mebutate may represent an interesting therapeutic option in
patients with mild immunosuppression.
PMID- 27513861
TI - HDACi Valproic Acid (VPA) and Suberoylanilide Hydroxamic Acid (SAHA) Delay but
Fail to Protect against Warm Hepatic Ischemia-Reperfusion Injury.
AB - BACKGROUND: Histone deacetylases (HDAC) catalyze N-terminal deacetylation of
lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In
various animal models, such as trauma/hemorrhagic shock, ischemic stroke or
myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and
organoprotective and promotes survival. HDACi reduce stress signaling, cell death
and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver
resection or transplantation increases morbidity and mortality. Assuming
protective properties, the aim of this study was to investigate the effect of the
HDACi VPA and SAHA on warm hepatic I/R. MATERIAL AND METHODS: Male Wistar-Kyoto
rats (age: 6-8 weeks) were randomized to VPA, SAHA, vehicle control (pre-)
treatment or sham-groups and underwent partial no-flow liver ischemia for 90
minutes with subsequent reperfusion for 6, 12, 24 and 60 hours. Injury and
regeneration was quantified by serum AST and ALT levels, by macroscopic aspect
and (immuno-) histology. HDACi treatment efficiency, impact on MAPK/SAPK
activation and Hippo-YAP signaling was determined by Western blot. RESULTS:
Treatment with HDACi significantly enhanced hyperacetylation of Histone H3-K9
during I/R, indicative of adequate treatment efficiency. Liver injury, as
measured by macroscopic aspect, serum transaminases and histology, was delayed,
but not alleviated in VPA and SAHA treated animals. Importantly, tissue
destruction was significantly more pronounced with VPA. SAPK-activation (p38 and
JNK) was reduced by VPA and SAHA in the early (6h) reperfusion phase, but
augmented later on (JNK, 24h). Regeneration appeared enhanced in SAHA and VPA
treated animals and was dependent on Hippo-YAP signaling. CONCLUSIONS: VPA and
SAHA delay warm hepatic I/R injury at least in part through modulation of SAPK
activation. However, these HDACi fail to exert organoprotective effects, in this
setting. For VPA, belated damage is even aggravated.
PMID- 27513863
TI - The Harm of Contact and Non-Contact Sexual Abuse: Health-Related Quality of Life
and Mental Health in a Population Sample of Swiss Adolescents.
PMID- 27513864
TI - Intricate Macrophage-Colorectal Cancer Cell Communication in Response to
Radiation.
AB - Both cancer and tumour-associated host cells are exposed to ionizing radiation
when a tumour is subjected to radiotherapy. Macrophages frequently constitute the
most abundant tumour-associated immune population, playing a role in tumour
progression and response to therapy. The present work aimed to evaluate the
importance of macrophage-cancer cell communication in the cellular response to
radiation. To address this question, we established monocultures and indirect co
cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal
cancer cells, which exhibit higher and lower radiation sensitivity, respectively.
Mono- and co-cultures were then irradiated with 5 cumulative doses, in a similar
fractionated scheme to that used during cancer patients' treatment (2
Gy/fraction/day). Our results demonstrated that macrophages sensitize RKO to
radiation-induced apoptosis, while protecting SW1463 cells. Additionally, the co
culture with macrophages increased the mRNA expression of metabolism- and
survival-related genes more in SW1463 than in RKO. The presence of macrophages
also upregulated glucose transporter 1 expression in irradiated SW1463, but not
in RKO cells. In addition, the influence of cancer cells on the expression of pro
and anti-inflammatory macrophage markers, upon radiation exposure, was also
evaluated. In the presence of RKO or SW1463, irradiated macrophages exhibit
higher levels of pro-inflammatory TNF, IL6, CCL2 and CCR7, and of anti
inflammatory CCL18. However, RKO cells induce an increase of macrophage pro
inflammatory IL1B, while SW1463 cells promote higher pro-inflammatory CXCL8 and
CD80, and also anti-inflammatory VCAN and IL10 levels. Thus, our data
demonstrated that macrophages and cancer cells mutually influence their response
to radiation. Notably, conditioned medium from irradiated co-cultures increased
non-irradiated RKO cell migration and invasion and did not impact on angiogenesis
in a chicken embryo chorioallantoic membrane assay. Overall, the establishment of
primary human macrophage-cancer cell co-cultures revealed an intricate cell
communication in response to ionizing radiation, which should be considered when
developing therapies adjuvant to radiotherapy.
PMID- 27513865
TI - The Relationship between T1 Sagittal Angle and Sagittal Balance: A Retrospective
Study of 119 Healthy Volunteers.
AB - T1 sagittal angle has been reported to be used as a parameter for assessing
sagittal balance and cervical lordosis. However, no study has been performed to
explore the relationship between T1 sagittal angle and sagittal balance, and
whether T1 sagittal angle could be used for osteotomy guidelines remains unknown.
The aim of our study is to explore the relationship between T1 sagittal angle and
sagittal balance, determine the predictors for T1 sagittal angle, and determine
whether T1 sagittal angle could be used for osteotomy guidelines to restore
sagittal balance. Medical records of healthy volunteers in our outpatient clinic
from January 2014 to August 2015 were reviewed, and their standing full-spine
lateral radiographs were evaluated. Demographic and radiological parameters were
collected and analyzed, including age, gender, T1 sagittal angle, maxTK, maxLL,
SS, PT, and PI. Correlation coefficients between T1 sagittal angle and other
spinopelvic parameters were determined. In addition, multiple regression analysis
was performed to establish predictive radiographic parameters for T1 sagittal
angle as the primary contributors. A total of 119 healthy volunteers were
recruited in our study with a mean age of 34.7 years. It was found that T1
sagittal angle was correlated with maxTK with very good significance (r = 0.697,
P<0.001), maxLL with weak significance (r = 0.206, P = 0.024), SS with weak
significance (r = 0.237, P = 0.009), PI with very weak significance (r = 0.189, P
= 0.039), SVA with moderate significance (r = 0.445, P<0.001), TPA with weak
significance (r = 0.207, P = 0.023), and T1SPI with weak significance (r = 0.309,
P = 0.001). The result of multiple regression analysis showed that T1 sagittal
angle could be predicted by using the following regression equation: T1 sagittal
angle = 0.6 * maxTK-0.2 * maxLL + 8. In the healthy population, T1 sagittal angle
could be considered as a useful parameter for sagittal balance; however, it could
not be thoroughly replaced for SVA. maxTK was the primary contributor to T1
sagittal angle. According to this equation, we could restore sagittal balance by
surgically changing thoracic kyphosis and lumbar lordosis, which could serve as a
guideline for osteotomy.
PMID- 27513866
TI - Sexual Health and Quality of Life Assessment among Ovarian Cancer Patients during
Chemotherapy.
AB - BACKGROUND: During the last decades many successful efforts have been made in
order to increase life expectancy in ovarian cancer (OC) patients. However, just
a few studies have investigated the impact of OC on quality of life (QoL) and
sexual function in OC cases during treatment. OBJECTIVE: The aim of this study
was to evaluate the QoL and sexual function of OC patients during chemotherapy
(CT). PATIENTS AND METHODS: Forty-nine subjects were enrolled and filled in the
European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28,
Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS)
questionnaires. The results were evaluated globally and consequently stratified
into several groups: single surgery versus multiple surgeries, age <=48 years
versus >48 years, and first-line CT versus multiple lines of CT. RESULTS:
Menopause-related symptoms, body image and attitude toward the disease were
significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006,
respectively). Sexual outcomes resulted in better scores in younger patients in
all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28
items: p = 0.022). Scores concerning body image, attitude toward the disease and
CT-associated symptoms resulted worse in patients after the first surgery (p =
0.017, p = 0.002 and p = 0.012, respectively). CONCLUSION: Our study confirms
that OC has a detrimental impact on QoL and intimacy, particularly in younger
patients, during the first course of CT and after the first cytoreductive
surgery.
PMID- 27513868
TI - Composite Hybrid Cluster Built from the Integration of Polyoxometalate and a
Metal Halide Cluster: Synthetic Strategy, Structure, and Properties.
AB - A step-by-step synthetic strategy, setting up a bridge between the
polyoxometalate (POM) and metal halide cluster (MHC) systems, is demonstrated to
construct an unprecedented composite hybrid cluster built up from one high
nuclearity cationic MHC [Cu8I6](2+) and eight Anderson-type anionic POMs
[HCrMo6O18(OH)6](2-) cross-linked by a tripodal alcohol derivative.
PMID- 27513867
TI - Crystal Structure of the SPOC Domain of the Arabidopsis Flowering Regulator FPA.
AB - The Arabidopsis protein FPA controls flowering time by regulating the alternative
3'-end processing of the FLOWERING LOCUS (FLC) antisense RNA. FPA belongs to the
split ends (SPEN) family of proteins, which contain N-terminal RNA recognition
motifs (RRMs) and a SPEN paralog and ortholog C-terminal (SPOC) domain. The SPOC
domain is highly conserved among FPA homologs in plants, but the conservation
with the domain in other SPEN proteins is much lower. We have determined the
crystal structure of Arabidopsis thaliana FPA SPOC domain at 2.7 A resolution.
The overall structure is similar to that of the SPOC domain in human SMRT/HDAC1
Associated Repressor Protein (SHARP), although there are also substantial
conformational differences between them. Structural and sequence analyses
identify a surface patch that is conserved among plant FPA homologs. Mutations of
two residues in this surface patch did not disrupt FPA functions, suggesting that
either the SPOC domain is not required for the role of FPA in regulating RNA 3'
end formation or the functions of the FPA SPOC domain cannot be disrupted by the
combination of mutations, in contrast to observations with the SHARP SPOC domain.
PMID- 27513869
TI - Utterances in infant-directed speech are shorter, not slower.
AB - It has become a truism in the literature on infant-directed speech (IDS) that IDS
is pronounced more slowly than adult-directed speech (ADS). Using recordings of
22 Japanese mothers speaking to their infant and to an adult, we show that
although IDS has an overall lower mean speech rate than ADS, this is not the
result of an across-the-board slowing in which every vowel is expanded equally.
Instead, the speech rate difference is entirely due to the effects of phrase
final lengthening, which disproportionally affects IDS because of its shorter
utterances. These results demonstrate that taking utterance-internal prosodic
characteristics into account is crucial to studies of speech rate.
PMID- 27513870
TI - When pumpkin is closer to onion than to squash: The structure of the second
language lexicon.
AB - The current research investigated the organization of the second language mental
lexicon. Twenty-seven English-Hebrew bilingual speakers (who spoke Hebrew as
their second language) completed a semantic fluency task in each of their
languages, and 24 native Hebrew speakers completed the task in Hebrew. Responses
were compared within and across groups, using computational tools. The analyses
indicated that the lexical network of the second language displayed greater local
connectivity and less modular community structure than the network in the native
language, both in the entire sample and in a sub-sample of bilinguals whose
Hebrew vocabulary was matched to that of the native Hebrew speakers. These
findings suggest that the lexical network of the second language is not as well
organized as is the network of the first language, even in highly proficient
bilinguals. The structural characteristics of the second language lexicon might
be affected by factors related to language learning history, including age of
acquisition and language use.
PMID- 27513871
TI - Word learning in linguistic context: Processing and memory effects.
AB - During language acquisition, children exploit syntactic cues within sentences to
learn the meanings of words. Yet, it remains unknown how this strategy develops
alongside an ability to access cues during real-time language comprehension. This
study investigates how on-line sensitivity to syntactic cues impacts off-line
interpretation and recall of word meanings. Adults and 5-year-olds heard novel
words embedded in sentences that were (1) consistent with an agent-first bias
(e.g., "The blicket will be eating the seal"->"the blicket" is an agent), (2)
required revision of this bias (e.g., "The blicket will be eaten by the seal"
>"the blicket" is a theme), or (3) weakened this bias through a familiar NP1
(e.g., "The seal will be eating/eaten by the blicket"->"the seal" is an agent or
theme). Across both ages, eye-movements during sentences revealed decreased
sensitivity to syntactic cues in contexts that required syntactic revision. In
children, the magnitude of on-line sensitivity was positively associated with the
accuracy of learning after the sentence. Parsing challenges during the word
learning task also negatively impacted children's later memory for word meanings
during a recall task. Altogether, these results suggest that real-time demands
impact word learning, through interpretive failures and memory interference.
PMID- 27513872
TI - Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous
Malformations in Ccm2-Deficient Mice.
AB - Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral
cavernous malformation in humans. Mouse models of CCM disease have been
established by deleting Ccm genes in postnatal animals. These mouse models
provide invaluable tools to investigate molecular mechanism and therapeutic
approaches for CCM disease. However, the full value of these animal models is
limited by the lack of an accurate and quantitative method to assess lesion
burden and progression. In the present study we have established a refined and
detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in
mouse brains. As this study utilized a voxel dimension of 9.5MUm (leading to a
minimum feature size of approximately 25MUm), it is therefore sufficient to
measure CCM lesion volume and number globally and accurately, and provide high
resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we
found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the
mouse hindbrain with similar total volume and number. This quantitative approach
also demonstrated a rescue of CCM lesions with simultaneous deletion of one
allele of Mekk3. This method would enhance the value of the established mouse
models to study the molecular basis and potential therapies for CCM and other
cerebrovascular diseases.
PMID- 27513873
TI - Requesting workplace accommodations: Impact of self-efficacy, outcome expectancy,
and positive affect.
AB - OBJECTIVE: The purpose of this study was to examine the impacts of self-efficacy,
outcome expectancy, and positive affect on intentions to request workplace
accommodations among people with disabilities (PWDs). METHOD: Seven-hundred and
fourteen adults with disabilities participated in an online survey study. This
study used structural equation modeling to examine the impact of self-efficacy,
outcome expectancy, and positive affect on intentions to request workplace
accommodations. RESULTS: The results showed that self-efficacy, outcome
expectancy, and positive affect accounted for 55.1% of the variance in
accommodation request intentions. CONCLUSIONS: Accommodation request is a complex
process that involves cognitive and affective factors for individuals with
disabilities. Rehabilitation professionals need to help PWDs boost their level of
self-efficacy and outcome expectancy by engaging in accommodation request and
goal-setting skills training. In addition, rehabilitation professionals should
assist PWDs to recognize the significance of positive affect in the process of
accommodation request. (PsycINFO Database Record
PMID- 27513874
TI - Mental health and professional help-seeking among college students with
disabilities.
AB - OBJECTIVE: Research has demonstrated that providing appropriate supports and
services on campus can improve both mental health and academic outcomes for
students with disabilities (Emerson, Honey, Madden, & Llewellyn, 2009; Stumbo,
Martin, & Hedrick, 2009), but little is known about the specific mental health
needs of this population. The purpose of this exploratory study, therefore, was
to identify the mental health needs of college students with various types of
disabilities. METHOD: Researchers analyzed data, collected by the Center for
Collegiate Mental Health, of 5,696 students with, and without, disabilities who
utilized counseling services on campuses in the 2013-14 academic year. A
nonclinical (students not in counseling) sample of 1,620 students with, and
without, disabilities was also explored. RESULTS: Compared to students without
disabilities, students with disabilities report more anxiety and academic-related
distress, as well as higher rates of suicide ideation, suicide attempts, and
nonsuicidal self-injury among both students in counseling and not in counseling.
CONCLUSIONS: Although in certain areas students with disabilities show similar
levels of distress as students without disabilities, students with disabilities
have higher levels of distress in areas which could impact their academic
success. Self-harming tendencies are higher for students with disabilities
overall, but more so for specific disability types. (PsycINFO Database Record
PMID- 27513875
TI - Clinical utility and characteristics of the brown location test for individuals
with right temporal lobe epilepsy.
AB - This Rehabilitation Measures Database summary provides a review of the
characteristics of the BLT for individuals with right temporal lobe epilepsy. A
full review of the BLT as well as reviews of over 300 other instruments can be
found at www.rehabmeasures.org. (PsycINFO Database Record
PMID- 27513876
TI - Second-Trimester Anterior Cervical Angle in a Low-Risk Population as a Marker for
Spontaneous Preterm Delivery.
AB - OBJECTIVE: The aim of this article is to assess the use of the anterior cervical
angle (ACA) as a predictor of spontaneous preterm delivery (sPTD) at 20+0-24+6
weeks of gestation in an unselected population. METHODS: We conducted a nested
case-control study that included 93 women who later delivered spontaneously <34
weeks of gestation and 225 controls. The ACA was assessed retrospectively on all
selected images using ImageJ(r) software. The concordance correlation coefficient
was determined for the assessment of interobserver variability. Continuous
variables were adjusted by maternal characteristics and expressed as the z-score
or multiples of the expected normal median (MoM) of the unaffected group.
Logistic regression analysis was used to evaluate whether any maternal
characteristics and ultrasound variables were significantly associated with sPTD
<34 weeks. RESULTS: ACA z-score values were significantly greater in women who
later delivered <34 weeks compared to controls (ACA z-score = 1.32 +/- 0.57 vs.
0.09 +/- 0.35; p = 0.035). The best prediction of sPTD <34 weeks was provided by
a model that combined cervical length (CL) MoM, ACA z-score and maternal
characteristics. For a fixed false-positive rate of 10%, the detection rate for
this model was 37.6%. CONCLUSION: A model combining maternal history, CL and ACA
at 20+0-24+6 weeks of gestation can predict approximately 40% of the severe
preterm births.
PMID- 27513877
TI - Should prophylactic measures to prevent postpolypectomy bleeding after resection
of large colorectal polyps be used?
AB - Post-polypectomy bleeding after colonoscopy with resection of large colorectal
polyps can cause significant morbidity (readmission for monitoring, transfusion,
repeat endoscopy and therapy) and a significant cost to hospitals and insurers.
Nevertheless prophylactic endoscopic measures could reduce risk of post
polypectomy bleeding. Searching in Epistemonikos database, which is maintained by
screening 30 databases, we identified two systematic reviews including 10
randomized trials. We combined the evidence using meta-analysis and generated a
summary of findings table following the GRADE approach. We concluded prophylactic
endoscopic measures could be effective in reducing post-polypectomy bleeding
after resection of large colorectal polyps.
PMID- 27513878
TI - Semantic parafoveal-on-foveal effects and preview benefits in reading: Evidence
from Fixation Related Potentials.
AB - During reading parafoveal information can affect the processing of the word
currently fixated (parafovea-on-fovea effect) and words perceived parafoveally
can facilitate their subsequent processing when they are fixated on (preview
effect). We investigated parafoveal processing by simultaneously recording eye
movements and EEG measures. Participants read word pairs that could be
semantically associated or not. Additionally, the boundary paradigm allowed us to
carry out the same manipulation on parafoveal previews that were displayed until
reader's gaze moved to the target words. Event Related Potentials time-locked to
the prime-preview presentation showed a parafoveal-on-foveal N400 effect.
Fixation Related Potentials time locked to the saccade offset showed an N400
effect related to the prime-target relationship. Furthermore, this later effect
interacted with the semantic manipulation of the previews, supporting a semantic
preview benefit. These results demonstrate that at least under optimal conditions
foveal and parafoveal information can be simultaneously processed and integrated.
PMID- 27513879
TI - To move or not to move? Exploring the relationship between residential mobility,
risk of cardiovascular disease and ethnicity in New Zealand.
AB - Residential mobility can have negative impacts on health, with some studies
finding that residential mobility can contribute to widening health gradients in
the population. However, ethnically differentiated experiences of residential
mobility and the relationship with health are neglected in the literature. To
examine the relationship between residential mobility, risk of cardiovascular
disease (CVD) and ethnicity, we constructed a cohort of 2,077,470 participants
aged 30 + resident in New Zealand using encrypted National Health Index (eNHI)
numbers linked to individual level routinely recorded data. Using binary logistic
regression, we model the risk of CVD for the population stratified by ethnic
group according to mover status, baseline deprivation and transitions between
deprivation statuses. We show that the relationship between residential mobility
and CVD varies between ethnic groups and is strongly influenced by the inter
relationship between residential mobility and deprivation mobility. Whilst
residential mobility is an important determinant of CVD, much of the variation
between ethnic groups is explained by contrasting deprivation experiences. To
reduce inequalities in CVD within New Zealand, policies must focus on
residentially mobile Maori, Pacific and South Asian populations who already have
a heightened risk of CVD living in more deprived areas.
PMID- 27513880
TI - Evaluation of Long-Term Cochlear Implant Use in Subjects With Acquired Unilateral
Profound Hearing Loss: Focus on Binaural Auditory Outcomes.
AB - INTRODUCTION: Cochlear implantation (CI) in subjects with unilateral profound
sensorineural hearing loss was investigated. The authors of the present study
demonstrated the binaural auditory outcomes in a 12- and 36-month prospective
cohort outcome study. The present study aimed to do a long-term (LT) evaluation
of the auditory outcomes in an analogous study group. DESIGN: LT evaluation was
derived from 12 single-sided deaf (SSD) CI recipients and from 11 CI recipients
with asymmetric hearing loss (AHL). A structured interview was conducted with
each subjects. Speech perception in noise and sound localization were assessed in
a CIOFF and in a CION condition. Four binaural effects were calculated: summation
effect (S0N0), squelch effect (S0NCI), combined head shadow effect (SCIN0), and
spatial release from masking (SRM). At the LT evaluation, the contribution of a
CI or a bone conduction device on speech perception in noise was investigated in
two challenging spatial configurations in the SSD group. RESULTS: All (23/23)
subjects wore their CI 7 days a week at LT follow-up evaluation, which ranged
from 3 to 10 years after implantation. In the SSD group, a significant combined
head shadow effect of 3.17 dB and an SRM benefit of 4.33 dB were found. In the
AHL group, on the other hand, the summation effect (2.00 dB), the squelch effect
(2.67 dB), the combined head shadow effect (3.67 dB), and SRM benefit (2.00 dB)
were significant at LT testing. In both the spatial challenging configurations,
the speech in noise results was significantly worse in the condition with the
bone conduction device compared with the unaided condition. No negative effect
was found for the CION condition. A significant benefit in the CION condition was
found for sound localization compared with the CIOFF condition in the SSD group
and in the AHL group. CONCLUSION: All subjects wore their CI 7 days a week at LT
follow-up evaluation. The presence of binaural effects has been demonstrated with
speech in noise testing, sound localization, and subjective evaluation. In the
AHL group, all investigated binaural effects were found to be significant. In the
SSD group on the other hand, only SRM and the head shadow, the two most robust
binaural effects, were significantly present. However, it took 12M before the SSD
and the AHL subjects significantly benefit from the head shadow effect. These
reported results could guide counseling of future CI candidates with SSD and AHL
in general.
PMID- 27513881
TI - Eye Movements in Strategic Choice.
AB - In risky and other multiattribute choices, the process of choosing is well
described by random walk or drift diffusion models in which evidence is
accumulated over time to threshold. In strategic choices, level-k and cognitive
hierarchy models have been offered as accounts of the choice process, in which
people simulate the choice processes of their opponents or partners. We recorded
the eye movements in 2 * 2 symmetric games including dominance-solvable games
like prisoner's dilemma and asymmetric coordination games like stag hunt and hawk
dove. The evidence was most consistent with the accumulation of payoff
differences over time: we found longer duration choices with more fixations when
payoffs differences were more finely balanced, an emerging bias to gaze more at
the payoffs for the action ultimately chosen, and that a simple count of
transitions between payoffs-whether or not the comparison is strategically
informative-was strongly associated with the final choice. The accumulator models
do account for these strategic choice process measures, but the level-k and
cognitive hierarchy models do not. (c) 2015 The Authors. Journal of Behavioral
Decision Making published by John Wiley & Sons Ltd.
PMID- 27513882
TI - Thrombomodulin enhances complement regulation through strong affinity
interactions with factor H and C3b-Factor H complex.
AB - INTRODUCTION: Coagulation and complement systems are simultaneously activated at
sites of tissue injury, leading to thrombin generation and opsonisation with C3b.
Thrombomodulin (TM) is a cell-bound regulator of thrombin activation, but can
also enhance the regulatory activity of complement factor H (FH), thus
accelerating the degradation of C3b into inactive iC3b. OBJECTIVES: This study
sought to determine the biophysical interaction affinities of two recombinant TM
analogs with thrombin, FH and C3b in order to analyze their ability to regulate
serum complement activity. METHODS: Surface plasmon resonance (SPR) analysis was
used to determine binding affinities of TM analogs with FH and C3b, and compared
to thrombin as positive control. The capacity of the two recombinant TM analogs
to regulate complement in serum was tested in standard complement hemolytic
activity assays. RESULTS: SPR analysis showed that both TM analogs bind FH and
C3b-Factor H with nanomolar and C3b with micromolar affinity; binding affinity
for its natural ligand thrombin was several fold higher than for FH. At a
physiological relevant concentration, TM inhibits complement hemolytic activity
in serum via FH dependent and independent mechanisms. CONCLUSIONS: TM exhibits
significant binding affinity for complement protein FH and C3b-FH complex and its
soluble form is capable at physiologically relevant concentrations of inhibiting
complement activation in serum.
PMID- 27513883
TI - Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and
heritability in a nationwide Swedish cohort.
AB - Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of
reproductive-aged women and characterized by high levels of circulating
androgens. Given that androgens have been implicated in the aetiology of several
psychiatric disorders, it was hypothesized that women with PCOS have high risk
for psychiatric comorbidity. We aimed to investigate this risk amongst women with
PCOS, as well as in their siblings, to elucidate if familial factors underlie any
potential associations. Using the Swedish national registers, we identified all
women diagnosed with PCOS between 1990 and 2013 (n=24,385), their full-siblings
(n=25,921), plus matched individuals (1:10/100) from the general population and
their full-siblings. Psychiatric disorder diagnoses were identified including
schizophrenia, bipolar disorder, depressive and anxiety disorders, eating
disorders, personality and gender identity disorder, autism spectrum disorder
(ASD), attention-deficit hyperactivity disorder (ADHD), tics, attempted and
completed suicide. Odds ratios (OR) and 95% confidence intervals (CI) were
estimated using conditional logistic regression and adjusted ORs (AOR) were
determined by adjustment for comorbid psychiatric disorders. Overall, women with
PCOS had an increased odds of having at least one psychiatric disorder (OR=1.56
[95CI%, 1.51-1.61]). Crude ORs showed associations with nearly all psychiatric
disorders included in this study. Following adjustment for comorbid psychiatric
disorders, women with PCOS were still at a significantly increased risk for
bulimia, schizophrenia, bipolar disorder, depressive and anxiety disorders,
personality disorders, with the highest AORs for ASD (AOR=1.55 [95%CI, 1.32
1.81]) and tics (AOR=1.65 [95%CI, 1.10-2.47]). Significantly higher AORs were
found for ASD in both brothers and sisters of women with PCOS, and for
depressive, anxiety, and schizophrenia spectrum disorders in the sisters only.
Notably, the crude ORs for attempted suicide were 40% higher in women with PCOS
and 16% higher in their unaffected sisters. However, the AORs were greatly
attenuated indicating that underlying psychiatric comorbidity is important for
this association. Women with PCOS had higher risks for a range of psychiatric
disorders not shown before. Elevated risk in their siblings suggests shared
familial factors between PCOS and psychiatric disorders. This study is an
important first step towards identifying the underlying mechanisms for risk of
psychiatric disorders in women with PCOS. Health professionals treating women
with PCOS should be aware that these patients - as well as their family members -
are important targets for mental health care.
PMID- 27513884
TI - Coarse-Grained Simulations of Polymer-Grafted Nanoparticles: Structural Stability
and Interfacial Behavior.
AB - In the tertiary oil recovery method known as "polymer flooding", the viscosity of
the injected water is increased by dissolving partially hydrolyzed polyacrylamide
so as to lower the mobility ratio and raise the vertical and areal sweep
efficiencies. However, its drawbacks include the degradation of the polymer in
the reservoir due to (1) shear while passing through chokes, perforations, and
pore throats, (2) morphological changes induced by divalent ions, and (3)
complete hydrolysis of the polymer at high temperatures. These factors adversely
affect the viscosity of the polymer flood. Past experimental research showed that
polymer-grafted nanoparticles (PNPs) could achieve the same viscosity enhancement
at lower quantities than traditional linear polymers. The PNPs have the putative
advantage of greater stability when confronted with the aforementioned reservoir
conditions. In this work, we use dissipative particle dynamics (DPD) to simulate
the oil-PNP-water system at the mesoscale and estimate its sensitivity to brine
in ways that could serve as guidelines to experiments. We study the effect of
salinity on the structure of linear and branched polyelectrolytes before
extending the DPD model to PNPs at the oil-water interface. To this end, we
parameterize the interactions of the polymer with the oil and water phases, and
broadly map out solvent conditions that change the graft's morphology and affect
the interfacial behavior of the grafted particle. We find that the equilibrium
location of the grafted nanoparticle in an oil-brine system depends on its
grafting density and the salinity.
PMID- 27513885
TI - Defining and Detecting Complex Peak Relationships in Mass Spectral Data: The
Mz.unity Algorithm.
AB - Analysis of a single analyte by mass spectrometry can result in the detection of
more than 100 degenerate peaks. These degenerate peaks complicate spectral
interpretation and are challenging to annotate. In mass spectrometry-based
metabolomics, this degeneracy leads to inflated false discovery rates, data sets
containing an order of magnitude more features than analytes, and an inefficient
use of resources during data analysis. Although software has been introduced to
annotate spectral degeneracy, current approaches are unable to represent several
important classes of peak relationships. These include heterodimers and higher
complex adducts, distal fragments, relationships between peaks in different
polarities, and complex adducts between features and background peaks. Here we
outline sources of peak degeneracy in mass spectra that are not annotated by
current approaches and introduce a software package called mz.unity to detect
these relationships in accurate mass data. Using mz.unity, we find that data sets
contain many more complex relationships than we anticipated. Examples include the
adduct of glutamate and nicotinamide adenine dinucleotide (NAD), fragments of NAD
detected in the same or opposite polarities, and the adduct of glutamate and a
background peak. Further, the complex relationships we identify show that several
assumptions commonly made when interpreting mass spectral degeneracy do not hold
in general. These contributions provide new tools and insight to aid in the
annotation of complex spectral relationships and provide a foundation for
improved data set identification. Mz.unity is an R package and is freely
available at https://github.com/nathaniel-mahieu/mz.unity as well as our
laboratory Web site http://pattilab.wustl.edu/software/ .
PMID- 27513886
TI - Association between serum vitamin D, retinol and zinc status, and acute
respiratory infections in underweight and normal-weight children aged 6-24 months
living in an urban slum in Bangladesh.
AB - We conducted a longitudinal assessment in 466 underweight and 446 normal-weight
children aged 6-24 months living in the urban slum of Dhaka, Bangladesh to
determine the association between vitamin D and other micronutrient status with
upper respiratory tract infection (URI) and acute lower respiratory infection
(ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable
generalized estimating equations. Our results indicate that underweight children
with insufficient and deficient vitamin D status were associated with 20% and 23
25% reduced risk of URI, respectively, compared to children with sufficient
status. Underweight children, those with serum retinol deficiency were at 1.8
[95% confidence interval (CI) 1.4-2.4] times higher risk of ALRI than those with
retinol sufficiency. In normal-weight children there were no significant
differences between different vitamin D status and the incidence of URI and ALRI.
However, normal-weight children with zinc insufficiency and those that were serum
retinol deficient had 1.2 (95% CI 1.0-1.5) times higher risk of URI and 1.9 (95%
CI 1.4-2.6) times higher risk of ALRI, respectively. Thus, our results should
encourage efforts to increase the intake of retinol-enriched food or
supplementation in this population. However, the mechanisms through which vitamin
D exerts beneficial effects on the incidence of childhood respiratory tract
infection still needs further research.
PMID- 27513887
TI - The class III peroxidase PRX17 is a direct target of the MADS-box transcription
factor AGAMOUS-LIKE15 (AGL15) and participates in lignified tissue formation.
AB - Several physiological functions have been attributed to class III peroxidases
(PRXs) in plants, but the in planta role of most members of this family still
remains undetermined. Here, we report the first functional characterization of
PRX17 (At2g22420), one of the 73 members of this family in Arabidopsis thaliana.
Localization of PRX17 was examined by transient expression in Nicotiana
benthamiana. Loss- and gain-of-function mutants in A. thaliana were studied.
Regulation at the gene and protein levels was analyzed using beta-glucuronidase
(GUS) activity, quantitative reverse transcriptase (qRT)-PCR, zymography, and
chromatin immunoprecipitation. Phenotypes were characterized including lignin and
xylan contents. PRX17 was expressed in various tissues, including vascular
tissues, and PRX17 was localized to the cell wall. In prx17, the lignin content
was reduced in the stem and siliques and bolting was delayed, while the opposite
phenotype was observed in 35S:PRX17 plants, together with a significant increase
of lignin and xylan immunofluorescence signal. Finally, we demonstrated that the
transcription factor AGAMOUS-LIKE15 (AGL15) binds to the PRX17 promoter and
regulates PRX17 expression level. This converging set of structural,
transcriptomic and physiological data suggests that PRX17, under the control of
AGL15, contributes to developmental programs by playing an essential role in
regulating age-dependent lignified tissue formation, including changes in cell
wall properties.
PMID- 27513888
TI - Follow up with HPV test and cytology as test of cure, 6 months after conization,
is reliable.
AB - INTRODUCTION: Human papillomavirus (HPV) infection is an objective marker with a
high sensitivity for finding cervical dysplasia. The objective of the current
study is to investigate whether HPV testing, combined with liquid-based cytology,
is reliable as a test of cure after the loop electrical excision procedure
(LEEP). MATERIAL AND METHODS: The LEEP was performed in 330 women for excision of
cervical dysplasia. Follow up consisted of HPV testing and liquid-based cytology
at six, 12, and 36 months after treatment. Patients with negative co-testing
after 6 months were re-examined after 3 years. Patients who tested positive for
high-risk HPV and/or dysplasia were followed up 12 months postoperatively.
RESULTS: At 6 months, the co-testing was double negative in 169 of 260 tested
cases (65%). A positive high-risk HPV test (n = 40) was associated with
cytological abnormalities (p < 0.001). After 3 years, 227 of 275 examined cases
(83%) co-tested negative, including 154 patients who had already tested negative
at 6 months and 37 cases with viral clearance at 12 months. Of 26 patients with
high-risk HPV at the 3-year follow up, six had LSIL findings on liquid-based
cytology, but neither HSIL lesions nor glandular atypia or cervical cancer was
found. A negative high-risk HPV test showed a negative predictive value for HSIL
of 100% (95% CI 99.8-100%). CONCLUSIONS: Negative co-testing 6 months after LEEP
can be considered a reliable test of cure as 3-year follow-up results are
consistent with neither HSIL or cancer.
PMID- 27513889
TI - The Planar Blatter Radical: Structural Chemistry of 1,4
Dihydrobenzo[e][1,2,4]triazin-4-yls.
AB - Two planarized analogues of the prototypical Blatter radical (1), peri-annulated
1S and 1O , are demonstrated and provide a new platform for molecular and
supramolecular engineering, and for tuning electronic and magnetic properties of
the radical. Planarization of 1 results in bathochromic shift to the near-IR
region, greater spin delocalization, and anodic shift of the reduction potential
only for 1S . Magnetization studies revealed nearly ideal paramagnetic behavior
at high temperatures for both radicals 1S and 1O with one-dimensional
ferromagnetic interaction in the former (2J=14.4 cm(-1) ) and antiferromagnetic
interactions in 1O at low temperatures.
PMID- 27513890
TI - Systematic Review and Meta-Analysis of Doxycycline Efficacy for Rectal
Lymphogranuloma Venereum in Men Who Have Sex with Men.
AB - Rectal lymphogranuloma venereum (LGV) has reemerged as a sexually transmitted
infection among men who have sex with men (MSM), particularly those who are HIV
positive. We undertook a systematic review and meta-analysis to determine the
efficacy of doxycycline (100 mg 2*/d for 21 days) for rectal LGV in MSM. Nine
studies were included: 4 prospective, 4 retrospective, and 1 combined
retrospective and prospective. In total, 282 MSM with rectal LGV were included in
the studies. All studies reported using nucleic acid amplification tests to
assess microbial cure. Most patients (>80%) had symptomatic rectal infection. The
fixed-effects pooled efficacy for doxycycline was 98.5% (95% CI 96.3%-100%, I (2)
= 0%; p = 0.993). Doxycycline at 100 mg twice daily for 21 days demonstrated a
high microbial cure rate. These data support doxycycline at this dosage and
duration as first-line therapy for rectal LGV in MSM.
PMID- 27513891
TI - CD10 down expression in follicular lymphoma correlates with gastrointestinal
lesion involving the stomach and large intestine.
AB - Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and
CD10, whereas downexpression of CD10 is occasionally experienced in
gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare
variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma
was reported. We investigated the clinicopathological and genetic features of
CD10 downexpressed (CD10down ) GI-FL. The diagnosis of CD10down FL was carried
out with a combination of pathological and molecular analyses. The incidence of
CD10down GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than
nodal FL (3.5%, P < 0.001). The difference was additionally significant between
GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs
3.5%, P < 0.001). Compared to CD10+ GI-FL, CD10down GI-FL significantly involved
the stomach or large intestine (P = 0.015), and additionally showed the
downexpression of BCL6 (P < 0.001). The follicular dendritic cell meshwork often
showed a duodenal pattern in the CD10down group (P = 0.12). Furthermore, a
lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which
indicated caution in the differentiation of mucosa-associated lymphoid tissue
lymphoma. Molecular analyses were undertaken in seven cases of CD10down GI-FL,
and an identical clone was found between CD10down follicles and CD10+ BCL2+
neoplastic follicles. In the diagnosis of cases with CD10down BCL2+ follicles,
careful examination with molecular studies should be carried out.
PMID- 27513894
TI - The Structure and Torsional Dynamics of Two Methyl Groups in 2-Acetyl-5
methylfuran as Observed by Microwave Spectroscopy.
AB - The molecular-beam Fourier transform microwave spectrum of 2-acetyl-5-methylfuran
is recorded in the frequency range 2-26.5 GHz. Quantum chemical calculations
calculate two conformers with trans or cis configuration of the acetyl group,
both of which are assigned in the experimental spectrum. All rotational
transitions split into quintets due to the internal rotations of two
nonequivalent methyl groups. By using the program XIAM, the experimental spectra
can be simulated with standard deviations within the measurement accuracy, and
yield well-determined rotational and internal rotation parameters, inter alia the
V3 potentials. Whereas the V3 barrier height of the ring-methyl rotor does not
change for the two conformers, that of the acetyl-methyl rotor differs by about
100 cm-1 . The predicted values from quantum chemistry are only on the correct
order of magnitude.
PMID- 27513892
TI - Targeting of the P2X7 receptor in pancreatic cancer and stellate cells.
AB - The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival
and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC)
is a deadly cancer and new markers and therapeutic targets are needed. PDAC is
characterized by a complex tumour microenvironment, which includes cancer and
pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover.
Our aim was to determine P2X7R expression and function in human pancreatic cancer
cells in vitro as well as to perform in vivo efficacy study applying P2X7R
inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies
we show that human PDAC cells with luciferase gene (PancTu-1 Luc cells) express
high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited
cell proliferation in basal conditions, indicating that P2X7R was tonically
active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive,
further affected cell survival and confirmed complex functionality of P2X7R.
PancTu-1 Luc migration and invasion was reduced by AZ10606120, and it was
stimulated by PSCs, but not by PSCs from P2X7(-/-) animals. PancTu-1 Luc cells
were orthotopically transplanted into nude mice and tumour growth was followed
noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced
bioluminescence compared to saline-treated mice. Immunohistochemical analysis
confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic
acinar and duct structures. PSCs number/activity and collagen deposition was
reduced in AZ10606120-treated tumours.
PMID- 27513895
TI - Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells
by modulating proliferation and apoptosis via targeting MET.
AB - Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric
cancer (GC) treatment. However, drug resistance is a major obstacle for DDP
chemotherapy. Recent studies indicated that the resistance could be modulated by
the regulation of dysregulated microRNAs (miRs). Previous study also found miR
34a was associated with cell proliferation and apoptosis in human GC; however,
the relationship between miR-34a and DDP resistance still remains unexplored. The
purpose of this study was to investigate whether miR-34a is associated with DDP
resistance in human GC cells. Our study found that the expression of miR-34a was
significantly decreased in DDP resistance human GC tissues and DDP resistance
human GC SGC7901/DDP cells compared with normal GC tissues and cells.
Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP
through the inhibition of cell proliferation and induction of cell apoptosis; on
the other hand downregulation of miR-34a could weaken the DDP sensitivity of
SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a
and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells.
Moreover, our study also indicated that up-regulation of miR-34a could decrease
the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR
34a could modulate human gastric cancer cell DDP sensitivity by regulation of
cell proliferation and apoptosis via targeting MET, potentially benefiting human
GC treatment in the future.
PMID- 27513896
TI - Anisotropic thermal motion in transition-metal carbonyls from experiments and ab
initio theory.
AB - The thermal motion of atoms in crystals is quantified by anisotropic displacement
parameters (ADPs). Here we show that dispersion-corrected periodic density
functional theory can be used to compute accurate ADPs for transition metal
carbonyls, which serve as model systems for crystalline organometallic and
coordination compounds.
PMID- 27513897
TI - Outpatient induction of labour in the UK: a survey of practice.
AB - OBJECTIVE: To identify the current UK use of outpatient procedures for cervical
ripening prior to induction of labour. STUDY DESIGN: Postal survey of consultant
led obstetric units within the United Kingdom. A questionnaire was sent by post
to 210 NHS consultant led obstetric units within the UK. Units that provided
outpatient induction of labour (OP IOL) were asked complete a series of questions
defining their protocol for risk stratification and management. RESULTS: The
survey had a 78% response rate. 17.6% of units stated that they currently or soon
will provide OP IOL. All units were willing to provide OP IOL for post-dates
singleton pregnancies and none provided this service for women with a previous
caesarean or multiple pregnancy. 96% of inductions were initiated in a hospital
setting prior to discharge home. 84% of units used Propess((r)) to initiate OP
IOL and 96% had a fetal assessment with CTG. Only 40% of units had a clear
mechanism for assessment once the woman had gone home. 72% of units performed
regular audit of their practice. CONCLUSIONS: We suggest that robust comparative
research within a UK context is urgently required to establish the safety and
cost effectiveness of outpatient induction of labour before this technique
becomes fully embedded in clinical care without an adequate evidence base.
PMID- 27513898
TI - Self-Monitoring of Intraocular Pressure Outside of Normal Office Hours Using
Rebound Tonometry: Initial Clinical Experience in Patients With Normal Tension
Glaucoma.
AB - PURPOSE: To determine the value and accuracy of 24-hour intraocular pressure
(IOP) phasing using Icare ONE rebound tonometry (RTONE), in subjects with normal
tension glaucoma (NTG). METHODS: Eighteen consecutive patients with treated NTG
were studied, all subjects had undergone 24-hour IOP phasing during a 1-year
period. Each patient had daytime (08:00 to 16:00) IOP phasing with Goldmann
applanation tonometer at 2-hourly intervals; at these same time points an IOP
reading was also obtained by the patient using RTONE. Self-measured IOPs were
then recorded at home using RTONE between 18:00 and 06:00 (at 2-hourly
intervals). The frequency with which the phasing results altered clinical
management was evaluated. RESULTS: The mean peak IOP was significantly higher
during nighttime phasing (15.78+/-4.8 mm Hg) compared with daytime phasing
(12.83+/-2.7 mm Hg, P=0.0018) and clinic IOP measurements (11.8+/-1.6 mm Hg,
P<0.0001). Following IOP phasing a change in management occurred in 10 of 18
patients (56%). In the majority of these patients, a peak IOP was identified
during nighttime phasing compared with daytime phasing, this difference was
significant (P=0.0090). There were strong correlations between the IOP
measurements obtained with Goldmann applanation tonometer and RTONE (Spearman r
values >0.60, P<0.001). CONCLUSIONS: This study suggests that in patients with
NTG with progression that is disproportionate to their clinic IOP measurements,
24-hour phasing can reveal higher IOP spikes than those identified during typical
office hours. RTONE is a safe, easy to use, and accurate device for self
monitoring of IOP.
PMID- 27513899
TI - Ab Interno Trabeculectomy With the Trabectome as a Valuable Therapeutic Option
for Failed Filtering Blebs.
AB - PURPOSE: Uncontrolled intraocular pressure (IOP) after glaucoma filtration
surgery is a challenging problem in the management of glaucoma patients. The
Trabectome is a device for selective electroablation of the trabecular meshwork
through a clear cornea incision without affecting the conjunctiva. Minimally
invasive glaucoma surgery using the Trabectome is safe and effective as primary
glaucoma surgery. Here we investigate the results of ab interno trabeculectomy
with the Trabectome for IOP control in patients with a failed filtering bleb.
METHODS: A total of 60 eyes of 60 consecutive patients with primary open-angle
glaucoma (POAG) or pseudoexfoliative glaucoma (PXG) were enrolled in this single
center observational study. Trabectome surgery was performed alone or in
combination with phacoemulsification by 2 experienced surgeons. IOP readings and
number of IOP lowering medication as primary outcome parameters were taken by an
independent examiner. Intraoperative and postoperative medication were recorded
systematically. RESULTS: Mean IOP before surgery was 24.5+/-3.5 mm Hg and
decreased to 15.7+/-3.4 (-36%) after mean follow-up of 415 days. The number of
necessary IOP lowering medication dropped from 2.1+/-1.3 to 1.8+/-1.2 (14%
reduction from baseline). A total of 25% (n=15) of cases reported here needed
additional surgery after 517 days (range: 6 to 1563 d). No major complications
were observed. After mean follow-up, we found a qualified success rate for PXG of
87% and 50% for POAG as revealed by the Kaplan-Meier analysis according to the
definitions for success in advanced glaucoma cases according to the World
Glaucoma Association (40% reduction from baseline IOP and maximum IOP of 15 mm
Hg). DISCUSSION: Trabectome surgery for uncontrolled IOP after trabeculectomy is
safe and effective especially in PXG patients. Given the demanding subgroup of
patients studied here, it is not surprising that success rates are lower compared
with previous studies investigating the Trabectome for primary glaucoma surgery.
The number of necessary IOP lowering medication drops at first, but seems to
reach preoperative values after 20 months of follow-up. Trabectome surgery should
be considered as a valuable escape procedure for patients with failed filtering
blebs and uncontrolled IOP.
PMID- 27513900
TI - Trabeculectomy and Combined Phacoemulsification-Trabeculectomy: Outcomes and Risk
Factors for Failure in Primary Angle Closure Glaucoma.
AB - PURPOSE: To evaluate tonometric outcomes of patients with primary angle closure
glaucoma (PACG) who have undergone trabeculectomy with mitomycin C (MMC) with and
without concurrent phacoemulsification and to identify risk factors for
postoperative failure. PATIENTS AND METHODS: Retrospective cohort study of 44
eyes of 33 phakic patients who underwent trabeculectomy with MMC with or without
combined phacoemulsification for PACG. The primary endpoint was qualified
tonometric success at 12 months according to predefined criteria. LogMAR visual
acuity, number of glaucoma medications, and postoperative complications were also
evaluated. Cox proportional hazard regression analysis was performed to identify
potential risk factors for trabeculectomy failure. RESULTS: Mean intraocular
pressure (IOP) decreased from 21.3+/-7.9 to 12.2+/-3.9 mm Hg at 12 months
(P<0.001) in all patients. A significant reduction in mean number of glaucoma
medications (P<0.001) was also seen. There was no change in logMAR visual acuity
(P=0.39) after 12 months. There were no significant intergroup differences in
mean IOP (P=0.42), number of glaucoma medications (P=0.85), or logMAR visual
acuity (P=0.42) between the trabeculectomy versus combined surgery groups after
12 months. Increased age, greater baseline IOP, limbus-based conjunctival flaps,
and MMC duration >1 minute were associated with decreased risk of surgical
failure. Concurrent phacoemulsification at the time of trabeculectomy did not
alter tonometric success or rate of complications. CONCLUSIONS: In phakic
patients with PACG, trabeculectomy with MMC significantly reduces IOP and number
of glaucoma medications at 12 months without change in visual acuity. However,
success rates are modest when based on more demanding tonometric criteria.
PMID- 27513901
TI - The Association of Chronic Topical Prostaglandin Analog Use With Meibomian Gland
Dysfunction.
AB - PURPOSE: To evaluate the association of long-term prostaglandin analog (PGA) use
with meibomian gland dysfunction (MGD) in medically treated glaucoma patients.
MATERIALS AND METHODS: This was a prospective cross-sectional study conducted at
a single academic setting. In total, 70 eyes of 70 patients with a medical
diagnosis of glaucoma who were on long-term (>12 mo) topical hypotensive
medication(s) were included. Patients were classified based on whether they were
on PGA or non-PGA class of medication(s). MGD was defined based on meibomian
gland terminal duct obstruction and graded between 1 and 5 based on severity. For
all subjects, ocular surface disease index questionnaire, break-up time,
lissamine green staining, and Schirmer test (under topical anesthesia) was
administered. Student t test, Mann-Whitney U test, and chi test was used in
statistical evaluations. Forty-five age-matched healthy control subjects who were
not on any topical medications were also included. RESULTS: In total, 25 patients
(35.7%) were on PGA monotherapy, 21 (30.0%) were treated with fixed or unfixed
PGA combination regimens, and 24 (34.3%) were on non-PGA medications. MGD
prevalence was higher in patients treated with PGA monotherapy (92.0%) compared
with those receiving non-PGA therapy (58.3%) (P=0.02). Obstructive type of MGD
was detected in the majority of patients treated with PGAs (95.7%). Grade 2 and 3
MGD was noted in 80.5% of patients on PGA. Patients on PGA had worse ocular
surface disease index and ocular surface test results (P<0.001) compared with
those of control subjects. CONCLUSIONS: Long-term administration of PGA is
associated with obstructive type of MGD.
PMID- 27513902
TI - Evaluation of Interocular Retinal Nerve Fiber Layer Thickness Symmetry as a
Diagnostic Modality for Glaucoma.
AB - PURPOSE OF THE STUDY: The purpose of study was to measure the diagnostic utility
of interocular retinal nerve fiber layer (RNFL) symmetry and interocular RNFL
thickness comparison. METHODS: Both eyes of 103 normal subjects and 106 glaucoma
patients (31 patients with early glaucoma and 75 patients with moderate to severe
glaucoma) received comprehensive ophthalmologic evaluation including visual field
testing and optic disc scanning using optical coherence tomography. RNFL
thickness values for 256 measurement points were rearranged according to a new
reference line connecting the optic disc center and the foveola. The interocular
RNFL thickness symmetry value and absolute and fractional interocular difference
in RNFL thickness were calculated and compared between groups. Area under the
receiver operating characteristic curves (AUROCs) were calculated and compared.
RESULT: Among the parameters reflecting whole RNFL status, the corrected
interocular RNFL thickness symmetry exhibited the largest AUROCs at all glaucoma
stages. RNFL thickness and absolute and fractional interocular difference in RNFL
thickness exhibited largest AUROC in the inferotemporal area, regardless of
glaucoma stage. In the early glaucoma group, absolute and fractional interocular
RNFL thickness differences in the temporal and superotemporal areas exhibited
equal to or larger AUROCs than RNFL thickness. The AUROCs for RNFL thickness were
greater than those for absolute and fractional interocular RNFL thickness
differences in the moderate to severe glaucoma group except in the nasal and
temporal area. CONCLUSIONS: The corrected interocular RNFL thickness symmetry
value is an effective diagnostic tool for glaucoma. Interocular comparison of
RNFL thickness has good diagnostic performance and gives information about the
RNFL beyond just the RNFL thickness itself.
PMID- 27513903
TI - Comparison of Smartphone Ophthalmoscopy With Slit-Lamp Biomicroscopy for Grading
Vertical Cup-to-Disc Ratio.
AB - PURPOSE OF THE STUDY: The purpose of the study was to determine the agreement
between smartphone ophthalmoscopy and slit-lamp indirect biomicroscopy when
assessing vertical cup-to-disc ratios (VCDRs). MATERIALS AND METHODS: This was a
clinical-based, prospective, comparative instrument study performed in 110
patients with ocular hypertension (OH) or primary open angle glaucoma (POAG).
Patients underwent estimation of VCDR by undilated smartphone ophthalmoscopy and
slit-lamp biomicroscopy by 2 masked glaucoma specialists. RESULTS: The
differences between the mean VCDR estimations obtained by each techniques were
not statistically significant. Overall exact agreement between the 2 modalities
was found in 21 of 29 eyes (72.4%; simple kappa=0.63, confidence interval, 0.52
0.73, P<0.001) in POAG patients and in 52 of 78 eyes (66.7%) in OH patients. The
optic nerve head was not gradable with smartphone ophthalmoscopy in 1 eye with
POAG and in 2 eyes with OH because of media opacities and/or small pupil
diameter. CONCLUSIONS: Smartphone ophthalmoscopy showed substantial agreement
with slit-lamp examination for the estimation of the VCDR. The ubiquitous
diffusion of the smartphones, together with their connectivity and portability
features, enables an extensive benefit for this technology to be used in glaucoma
screening, especially in low-resource settings.
PMID- 27513904
TI - Acquired Corneal Neuropathy and Photoallodynia Associated With Malposition of an
Ex-PRESS Shunt.
AB - PURPOSE: Corneal neuropathy is a recently described disease process that is not
well understood and is likely underdiagnosed as a result. This is the first
reported case of an acquired corneal neuropathy associated with malposition of an
Ex-PRESS shunt. METHODS: A single case report. RESULTS: We report the case of a
50-year-old man with a history of multiple procedures for glaucoma who
subsequently developed photoallodynia and corneal neuropathy in association with
malposition of an Ex-PRESS shunt in the peripheral cornea. Laser confocal
microscopy (HRT3/RCM) of the cornea showed the presence of neuromas, decreased
nerve density, and a significant increase of dendritiform immune cells consistent
with our diagnosis. Initial treatment with steroid pulse therapy did not result
in decreased inflammation or symptomatic improvement leading to surgical
explantation of the shunt. One month after surgery, there was noticeable
improvement in the patient's pain and photoallodynia (approximately 40%) as well
as the abnormalities seen on confocal microscopy. CONCLUSIONS: We hypothesize
that poor Ex-PRESS shunt positioning can act as a nidus for corneal inflammation,
resulting in corneal neuropathy and lowering of the nociception threshold.
PMID- 27513905
TI - Intraocular Pressure Outcomes Following Transscleral Diode Cyclophotocoagulation
Using Long and Short Duration Burns.
AB - PURPOSE: The purpose of this study was to compare outcomes of transscleral diode
cyclophotocoagulation using short duration (SD) versus longer duration (LD)
treatment. PATIENTS AND METHODS: Data were collected retrospectively on patients
with glaucoma who underwent cyclophotocoagulation with LD (4000 ms) treatment
with variable power <=1000 mW versus SD using 1500 ms with variable power <=2000
mW. The outcome measures included: intraocular pressure (IOP) at 12 months,
decrease in number of antiglaucoma medications, complications and visual acuity
(VA) at the final follow-up visit. RESULTS: There were 71 patients and 70
patients in the SD and LD groups, respectively. The mean IOP+/-SD pretreatment
baseline was 33+/-10 versus 36+/-10 mm Hg for SD and LD groups, respectively
(P>0.05). At 1 year postoperatively, the IOP decreased significantly in both
groups (16.7 vs. 17.4 mm Hg for SD and LD, respectively; P<0.0001). This decrease
in IOP was comparable between groups (P=0.5). The average number of IOP lowering
medications were 2.5 and 2.9 at baseline in the SD and LD groups, respectively,
and decreased to 1.3 in both groups (P=0.83). The mean LogMAR VA decreased
significantly from 1.87 at baseline to 1.96 at 1 year in the SD group (P=0.276),
and 2.03 to 2.3 (P<=0.001) in the LD group, this change was comparable (0.19;
P=0.075) between the 2 groups. Complications were also comparable. CONCLUSIONS:
Both LD and SD burns during cyclophotocoagulation effectively lowered IOP at 1
year. Neither treatment resulted in a greater reduction of IOP. LD treatment
appeared to result in a decrease in VA and greater postoperative inflammation.
PMID- 27513906
TI - Progressive Retinal Nerve Fiber Layer Atrophy Associated With Enlarging
Peripapillary Pit.
AB - PURPOSE: To report a case in which progressive retinal nerve fiber layer (RNFL)
atrophy was observed along with enlargement of the peripapillary pit. PATIENTS
AND METHODS: A 34-year-old male was diagnosed with primary open-angle glaucoma
and followed up for 4 years with regular ophthalmic examinations. Both eyes were
myopic (-10 D, OD and -10.5 D, OS), and untreated intraocular pressures were 18
mm Hg (OD) and 16 mm Hg (OS). RESULTS: A subtle depression of the superotemporal
peripapillary area was deepened and emerged as a peripapillary pit during the
follow-up period. With the enlargement of the peripapillary pit, a RNFL defect at
the location of pit widened and thinned continuously. The enlargement of the pit
was documented by the spectral-domain optical coherence tomography posterior pole
scanning. CONCLUSIONS: Progressive RNFL atrophy was observed with enlargement of
the peripapillary pit. The finding suggests that tensile stress derived from the
scleral stretching may have significant influence on the integrity of the RNFL.
PMID- 27513907
TI - Corneal Densitometry: A New Technique for Objective Assessment of Corneal Clarity
in Pseudoexfoliation Syndrome.
AB - PURPOSE: To evaluate the corneal clarity quantitatively by using corneal
densitometry in patients with pseudoexfoliation syndrome (PES) and to compare the
results with those of healthy control subjects. MATERIALS AND METHODS: Corneal
densitometry measurement of patients with bilateral PES and healthy control
subjects was carried out by Scheimpflug corneal topography (PentacamHR). For
densitometry analysis, the 12-mm diameter area of the cornea was subdivided into
4 concentric radial zones (0 to 2, 2 to 6, 6 to 10, 10 to 12 mm) and also into
anterior, central, and posterior layers based on corneal depth. Corneal
densitometry measurements were expressed in gray scale unit and only the data
from the right eyes of subjects were used for statistical analysis. RESULTS: A
total of 176 patients [89 with PES (52 male, 37 female) and 87 healthy control
subjects (52 male, 35 female)] were enrolled in the study. There was no
significant difference between the mean corneal densitometry values at anterior
120 MUm, central, and posterior 60 MUm of the cornea in all concentric radial
zones (P>0.05 for all). Corneal densitometry was positively correlated with age
in both groups (r=0.558, P<0.001 in PES; r=0.584, P<0.001 in control group).
CONCLUSIONS: Corneal densitometry that enables the objective assessment of
corneal clarity was found to be similar in patients with bilateral PES and
healthy control subjects. It is positively correlated with increasing age in both
groups. However, microstructural changes that contribute to the corneal
densitometry and the clinical relevance of these findings should be further
highlighted in future studies.
PMID- 27513908
TI - Temperate Assumptions: How Where We Work Influences How We Think.
AB - Scientists have been observing the natural world for centuries and have long been
intrigued by the high biodiversity and complexity of the tropics. They also
usually had North American or European-in other words, outsider-perspectives and
frequently concluded that the tropics were qualitatively different from the
temperate regions in their ecology, evolution, and behavior. In particular, the
tropics were seen as having a more benign abiotic environment, which in turn
fostered more complex biotic relationships, with increased competition and other
interactions. This may or may not be the case. Regardless, these ideas establish
the temperate regions of the world as a kind of model system, a norm to which the
tropics are compared and seen as different or unusual. The tropics are warmer or
more diverse, rather than the temperate zone being cooler or less diverse. Such
an attitude makes it difficult both to appreciate the scope of variation in
nature and to develop accurate and general models for ecological and evolutionary
processes.
PMID- 27513909
TI - Ecological Causes and Consequences of Intratropical Migration in Temperate
Breeding Migratory Birds.
AB - New discoveries from direct tracking of temperate-breeding passerines show that
intratropical migration (ITM) occurs in a growing number of species, which has
important implications for understanding their evolution of migration, population
dynamics, and conservation needs. Our large sample size ([Formula: see text]) for
purple martins (Progne subis subis) tracked with geolocators to winter sites in
Brazil, combined with geolocator deployments at breeding colonies across North
America, allowed us to test hypotheses for ITM, something which has not yet been
possible to do for other species. ITM in purple martins was not obligate; only
44% of individuals exhibited ITM, and movements were not coordinated in time or
space. We found no evidence to support the resource hypothesis; rainfall and
temperature experienced by individual birds during their last 2 weeks at their
first roost site were similar to conditions at their second roost site after ITM.
Birds generally migrated away from the heavily forested northwestern Amazon to
less forested regions to the south and east. ITM in this aerial insectivore
appears to support the competition-avoidance hypothesis and may be triggered by
increasing local density in the core wintering region. Full life cycle models and
migratory networks will need to incorporate ITM to properly address seasonal
carryover effects and identify which wintering regions are most important for
conservation.
PMID- 27513910
TI - Polyandry, Predation, and the Evolution of Frog Reproductive Modes.
AB - Frog reproductive modes are complex phenotypes that include egg/clutch
characteristics, oviposition site, larval development, and sometimes, parental
care. Two evident patterns in the evolution of these traits are the higher
diversity of reproductive modes in the tropics and the apparent progression from
aquatic to terrestrial reproduction, often attributed to higher fitness resulting
from decreased predation on terrestrial eggs and tadpoles. Here, we propose that
sexual selection-and not only natural selection due to predation-favors
terrestrial breeding by reducing the loss of fitness due to polyandry. To examine
this novel selective mechanism, we reconstructed the evolution of reproductive
diversity in two frog families (Hylidae and Leptodactylidae) and tested for
concerted evolution of egg and tadpole development sites with specific mating
behaviors. We found that oviposition and tadpole development sites are evolving
independently, do not show the same diversity and/or directionality in terms of
terrestriality, and thus may be diversifying due to different selective
mechanisms. In both families, terrestrial egg deposition is correlated with
amplexus that is hidden from competing males, and in hylids, testes mass was
significantly larger and more variable in males with exposed amplexus that are
vulnerable to polyandry. Our results indicate that intrasexual selection has been
an underappreciated mechanism promoting diversification of frog reproductive
modes.
PMID- 27513911
TI - Biogeochemistry and Geographical Ecology: Embracing All Twenty-Five Elements
Required to Build Organisms.
AB - Biogeochemistry is a key but relatively neglected part of the abiotic template
that underlies ecology. The template has a geography, one that is increasingly
being rearranged in this era of global change. Justus von Liebig's law of the
minimum has played a useful role in focusing attention on biogeochemical
regulation of populations, but given that ~25+ elements are required to build
organisms and that these organisms use and deplete nutrients in aggregates of
communities and ecosystems, we make the case that it is time to move on. We
review available models that suggest the many different mechanisms that give rise
to multiple elements, or colimitation. We then review recent empirical data that
show that rates of decomposition and primary productivity may be limited by
multiple elements. In that light, given the tropics' high species diversity and
generally more weathered soils, we predict that colimitation at community and
ecosystem scales is more prevalent closer to the equator. We conclude with
suggestions for how to move forward with experimental studies of colimitation.
PMID- 27513912
TI - Is There a Temperate Bias in Our Understanding of How Climate Change Will Alter
Plant-Herbivore Interactions? A Meta-analysis of Experimental Studies.
AB - Climate change can drive major shifts in community composition and interactions
between resident species. However, the magnitude of these changes depends on the
type of interactions and the biome in which they take place. We review the
existing conceptual framework for how climate change will influence tropical
plant-herbivore interactions and formalize a similar framework for the temperate
zone. We then conduct the first biome-specific tests of how plant-herbivore
interactions change in response to climate-driven changes in temperature,
precipitation, ambient CO2, and ozone. We used quantitative meta-analysis to
compare predicted and observed changes in experimental studies. Empirical studies
were heavily biased toward temperate systems, so testing predicted changes in
tropical plant-herbivore interactions was virtually impossible. Furthermore, most
studies investigated the effects of CO2 with limited plant and herbivore species.
Irrespective of location, most studies manipulated only one climate change factor
despite the fact that different factors can act in synergy to alter responses of
plants and herbivores. Finally, studies of belowground plant-herbivore
interactions were also rare; those conducted suggest that climate change could
have major effects on belowground subsystems. Our results suggest that there is a
disconnection between the growing literature proposing how climate change will
influence plant-herbivore interactions and the studies testing these predictions.
General conclusions will also be hampered without better integration of above-
and belowground systems, assessing the effects of multiple climate change factors
simultaneously, and using greater diversity of species in experiments.
PMID- 27513913
TI - Macroecology of Sexual Selection: A Predictive Conceptual Framework for Large
Scale Variation in Reproductive Traits.
AB - Abiotic factors exert direct and indirect influences on behavioral,
morphological, and life-history traits. Because some of these traits are related
to reproduction, there is a causal link between climatic conditions and the
expression of reproductive traits. This link allows us to generate predictions on
how reproductive traits vary in large geographic scales. Here we formalize this
macroecological framework, present some general predictions, and explore
empirical examples using harvestmen as study organisms. Our results show that the
length of breeding season in harvestmen is primarily influenced by the number of
warm months and that precipitation plays a secondary role in modulating the
period devoted to reproduction. Moreover, we show that the probability of
resource defense polygyny increases with longer breeding seasons and that the
presence of this type of mating system positively affects the magnitude of sexual
dimorphism in harvestmen. Finally, the presence of postovipositional parental
care is also influenced by the length of breeding season but not by actual
evapotranspiration, which is our proxy for the intensity of biotic interactions.
We argue that the macroecological framework proposed here may be a fruitful field
of investigation, with important implications for our understanding of sexual
selection and the evolution of reproductive traits in both animals and plants.
PMID- 27513914
TI - Geographical Variation in the Availability of Natural History Field Guides?
Personal Reflections, Causes, and Consequences.
PMID- 27513915
TI - Differential functional readthrough over homozygous nonsense mutations
contributes to the bleeding phenotype in coagulation factor VII deficiency.
AB - : Essentials Potentially null homozygous Factor(F)7 nonsense mutations are
associated to variable bleeding symptoms. Readthrough of p.Ser112X (life
threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough
mediated insertion of wild-type or tolerated residues produce functional
proteins. Functional readthrough over homozygous F7 nonsense mutations
contributes to the bleeding phenotype. SUMMARY: Background Whereas the rare
homozygous nonsense mutations causing factor (F)VII deficiency may predict null
conditions that are almost completely incompatible with life, they are associated
with appreciable differences in hemorrhagic symptoms. The misrecognition of
premature stop codons (readthrough) may account for variable levels of functional
full-length proteins. Objectives To experimentally evaluate the basal and drug
induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X
nonsense mutations that are associated with moderate (132X) or life-threatening
(112X) symptoms, and that are predicted to undergo readthrough with (132X) or
without (112X) production of wild-type FVII. Methods We transiently expressed
recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney
293 cells, and evaluated secreted FVII protein and functional levels by ELISA,
activated FX generation, and coagulation assays. Results The levels of functional
FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% +/- 0.2% of
wild-type rFVII; rFVII-112X, 0.5% +/- 0.1% of wild-type rFVII) were compatible
with the occurrence of spontaneous readthrough, which was magnified by the
addition of G418 - up to 12% of the wild-type value for the rFVII-132X nonsense
variant. The predicted missense variants arising from readthrough abolished
(rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22-45% of wild-type levels)
secretion and function. These data suggest that the appreciable rescue of
p.Cys132X function was driven by reinsertion of the wild-type residue, whereas
the minimal p.Ser112X function was explained by missense changes permitting FVII
secretion and function. Conclusions The extent of functional readthrough might
explain differences in the bleeding phenotype of patients homozygous for F7
nonsense mutations, and prevent null conditions even for the most readthrough
unfavorable mutations.
PMID- 27513916
TI - Chronic lithium treatment rectifies maladaptive dopamine release in the nucleus
accumbens.
AB - Chronic lithium treatment effectively reduces behavioral phenotypes of mania in
humans and rodents. The mechanisms by which lithium exerts these actions are
poorly understood. Pre-clinical and clinical evidence have implicated increased
mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic
voltammetry to characterize changes in extracellular DA concentrations in the
nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the
ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or
chronically with lithium. The effects of chronic lithium treatment on the
availability of DA for release were assessed by depleting readily releasable DA
using short inter-train intervals, or administering d-amphetamine acutely to
mobilize readily releasable DA. Chronic, but not acute, lithium treatment
decreased the amplitude of DA responses in the NAc following 60 Hz pulse train
stimulation. Neither lithium treatment altered the kinetics of DA release or
reuptake. Chronic treatment did not impact the progressive reduction in the
amplitude of DA responses when, using 20 or 60 Hz pulse trains, the VTA was
stimulated every 6 s to deplete DA. Specifically, the amplitude of DA responses
to 60 Hz pulse trains was initially reduced compared to control mice, but by the
fifth pulse train, there was no longer a treatment effect. However, chronic
lithium treatment attenuated d-amphetamine-induced increases in DA responses to
20 Hz pulse trains stimulation. Our data suggest that long-term administration of
lithium may ameliorate mania phenotypes by normalizing the readily releasable DA
pool in VTA axon terminals in the NAc. Read the Editorial Highlight for this
article on Page 520.
PMID- 27513917
TI - OMPcontact: An Outer Membrane Protein Inter-Barrel Residue Contact Prediction
Method.
AB - In the two transmembrane protein types, outer membrane proteins (OMPs) perform
diverse important biochemical functions, including substrate transport and
passive nutrient uptake and intake. Hence their 3D structures are expected to
reveal these functions. Because experimental structures are scarce, predicted 3D
structures are more adapted to OMP research instead, and the inter-barrel residue
contact is becoming one of the most remarkable features, improving prediction
accuracy by describing the structural information of OMPs. To predict OMP
structures accurately, we explored an OMP inter-barrel residue contact prediction
method: OMPcontact. Multiple OMP-specific features were integrated in the method,
including residue evolutionary covariation, topology-based transmembrane segment
relative residue position, OMP lipid layer accessibility, and residue evolution
conservation. These features describe the properties of a residue pair in
different respects: sequential, structural, evolutionary, and biochemical. Within
a 3-residues slide window, a Support Vector Machine (SVM) could accurately
determinate the inter-barrel contact residue pair using above features. A 5-fold
cross-valuation process was applied in testing the OMPcontact performance against
a non-redundant OMP set with 75 samples inside. The tests compared four
evolutionary covariation methods and screen analyzed the adaptive ones for inter
barrel contact prediction. The results showed our method not only efficiently
realized the prediction, but also scored the possibility for residue pairs
reliably. This is expected to improve OMP tertiary structure prediction.
Therefore, OMPcontact will be helpful in compiling a structural census of outer
membrane protein.
PMID- 27513919
TI - Differences in sensitivity to parenting depending on child temperament: A meta
analysis.
AB - Several models of individual differences in environmental sensitivity postulate
increased sensitivity of some individuals to either stressful (diathesis-stress),
supportive (vantage sensitivity), or both environments (differential
susceptibility). In this meta-analysis we examine whether children vary in
sensitivity to parenting depending on their temperament, and if so, which model
can best be used to describe this sensitivity pattern. We tested whether
associations between negative parenting and negative or positive child adjustment
as well as between positive parenting and positive or negative child adjustment
would be stronger among children higher on putative sensitivity markers
(difficult temperament, negative emotionality, surgency, and effortful control).
Longitudinal studies with children up to 18 years (k = 105 samples from 84
studies, Nmean = 6,153) that reported on a parenting-by-temperament interaction
predicting child adjustment were included. We found 235 independent effect sizes
for associations between parenting and child adjustment. Results showed that
children with a more difficult temperament (compared with those with a more easy
temperament) were more vulnerable to negative parenting, but also profited more
from positive parenting, supporting the differential susceptibility model.
Differences in susceptibility were expressed in externalizing and internalizing
problems and in social and cognitive competence. Support for differential
susceptibility for negative emotionality was, however, only present when this
trait was assessed during infancy. Surgency and effortful control did not
consistently moderate associations between parenting and child adjustment,
providing little support for differential susceptibility, diathesis-stress, or
vantage sensitivity models. Finally, parenting-by-temperament interactions were
more pronounced when parenting was assessed using observations compared to
questionnaires. (PsycINFO Database Record
PMID- 27513920
TI - Bone regeneration in mandibular fractures after the application of autologous
mesenchymal stem cells, a randomized clinical trial.
AB - BACKGROUND/AIM: Facial injury in adults can commonly result in fractures of the
mandible. Autologous mesenchymal stem cells (AMSCs) transplantation is proposed
as an alternative to conventional graft treatment to improve bone regeneration.
The aim was to evaluate the effectiveness of AMSCs application in mandibular
fractures to reduce regeneration time and increase bone quality. MATERIALS AND
METHODS: This study was a single-blind controlled clinical trial conducted in
patients with mandibular angle fractures. Patients were divided into two groups:
study group fracture reduction plus application of AMSCs and control group only
fracture reduction. AMSCs were obtained from adipose tissue 24 h before the
procedure. Intensity and density were evaluated in normal bone and fractured bone
at 4 and 12 weeks after surgery using panoramic radiography and computed
tomography. RESULTS: A total of 20 patients, 10 in each group, were included. The
study group had a mean age of 31.2 +/- 6.3 years, and the control group mean age
was 29.7 +/- 7.2 years. All patients were male. Bone quality measured in grey
levels at week 4 was 108.82 +/- 3.4 vs 93.92 +/- 2.6 (P = 0.000) using panoramic
radiography and 123 +/- 4.53 vs 99.72 +/- 5.72 (P = 0.000) using computed
tomography. At week 12, the measurements were 153.53 +/- 1.83 vs 101.81 +/- 4.83
(P = 0.000) using panoramic radiography and 165.4 +/- 4.2 vs 112.9 +/- 2.0 (P =
0.000) using tomography in the study and control groups, respectively.
CONCLUSION: Similar ossification values were obtained after 4 weeks when the use
of AMSCs was compared to simple fracture reduction. However, after 12 weeks, the
AMSCs group had a 36.48% higher ossification rate.
PMID- 27513921
TI - Cobalt Carbonate Hydroxide Nanowire Array on Ti Mesh: An Efficient and Robust 3D
Catalyst for On-Demand Hydrogen Generation from Alkaline NaBH4 Solution.
AB - In this work, for the first time, a cobalt carbonate hydroxide (Co(CO3 )0.5
(OH)?0.11 H2 O) nanowire array on Ti mesh (CHNA/Ti) was applied to drive the
dehydrogenation of alkaline NaBH4 solution for on-demand hydrogen production.
Compared with other nanostructured Co-based catalyst systems, CHNA/Ti can be
activated more quickly and separated easily from fuel solutions. This self
supported cobalt salt nanowire array catalyst works as an efficient and robust 3D
catalyst for the hydrolysis reaction of NaBH4 with a hydrogen generation rate of
4000 mL min-1 gCo-1 and a low apparent activation energy of 39.78 kJ mol-1 and
offers an attractive system for on-demand hydrogen generation.
PMID- 27513922
TI - Differences in sensitivity to microstructure between cyclic- and impact-based
microindentation of human cortical bone.
AB - Unlike the known relationships between traditional mechanical properties and
microstructural features of bone, the factors that influence the mechanical
resistance of bone to cyclic reference point microindention (cRPI) and impact
microindention (IMI) have yet to be identified. To determine whether cRPI and IMI
properties depend on microstructure, we indented the tibia mid-shaft, the distal
radius, and the proximal humerus from 10 elderly donors using the BioDent and
OsteoProbe (neighboring sites). As the only output measure of IMI, bone material
strength index (BMSi) was significantly different across all three anatomical
sites being highest for the tibia mid-shaft and lowest for the proximal humerus.
Total indentation distance (inverse of BMSi) was higher for the proximal humerus
than for the tibia mid-shaft but was not different between other anatomical
comparisons. As a possible explanation for the differences in BMSi, pore water,
as determined by 1 H nuclear magnetic resonance, was lowest for the tibia and
highest for the humerus. Moreover, the local intra-cortical porosity, as
determined by micro-computed tomography, was negatively correlated with BMSi for
both arm bones. BMSi was also positively correlated with peak bending stress of
cortical bone extracted from the tibia mid-shaft. Microstructural correlations
with cRPI properties were not significant for any of the bones. The one exception
was that average energy dissipated during cRPI was negatively correlated with
local tissue mineral density in the tibia mid-shaft. With higher indentation
force and larger tip diameter than cRPI, only IMI appears to be sensitive to the
underlying porosity of cortical bone. (c) 2016 Orthopaedic Research Society.
Published by Wiley Periodicals, Inc. J Orthop Res 35:1442-1452, 2017.
PMID- 27513923
TI - Angiogenic Factor AGGF1 Activates Autophagy with an Essential Role in Therapeutic
Angiogenesis for Heart Disease.
AB - AGGF1 is an angiogenic factor with therapeutic potential to treat coronary artery
disease (CAD) and myocardial infarction (MI). However, the underlying mechanism
for AGGF1-mediated therapeutic angiogenesis is unknown. Here, we show for the
first time that AGGF1 activates autophagy, a housekeeping catabolic cellular
process, in endothelial cells (ECs), HL1, H9C2, and vascular smooth muscle cells.
Studies with Atg5 small interfering RNA (siRNA) and the autophagy inhibitors
bafilomycin A1 (Baf) and chloroquine demonstrate that autophagy is required for
AGGF1-mediated EC proliferation, migration, capillary tube formation, and aortic
ring-based angiogenesis. Aggf1+/- knockout (KO) mice show reduced autophagy,
which was associated with inhibition of angiogenesis, larger infarct areas, and
contractile dysfunction after MI. Protein therapy with AGGF1 leads to robust
recovery of myocardial function and contraction with increased survival,
increased ejection fraction, reduction of infarct areas, and inhibition of
cardiac apoptosis and fibrosis by promoting therapeutic angiogenesis in mice with
MI. Inhibition of autophagy in mice by bafilomycin A1 or in Becn1+/- and Atg5 KO
mice eliminates AGGF1-mediated angiogenesis and therapeutic actions, indicating
that autophagy acts upstream of and is essential for angiogenesis.
Mechanistically, AGGF1 initiates autophagy by activating JNK, which leads to
activation of Vps34 lipid kinase and the assembly of Becn1-Vps34-Atg14 complex
involved in the initiation of autophagy. Our data demonstrate that (1) autophagy
is essential for effective therapeutic angiogenesis to treat CAD and MI; (2)
AGGF1 is critical to induction of autophagy; and (3) AGGF1 is a novel agent for
treatment of CAD and MI. Our data suggest that maintaining or increasing
autophagy is a highly innovative strategy to robustly boost the efficacy of
therapeutic angiogenesis.
PMID- 27513924
TI - Efficient Gene Tree Correction Guided by Genome Evolution.
AB - MOTIVATIONS: Gene trees inferred solely from multiple alignments of homologous
sequences often contain weakly supported and uncertain branches. Information for
their full resolution may lie in the dependency between gene families and their
genomic context. Integrative methods, using species tree information in addition
to sequence information, often rely on a computationally intensive tree space
search which forecloses an application to large genomic databases. RESULTS: We
propose a new method, called ProfileNJ, that takes a gene tree with statistical
supports on its branches, and corrects its weakly supported parts by using a
combination of information from a species tree and a distance matrix. Its low
running time enabled us to use it on the whole Ensembl Compara database, for
which we propose an alternative, arguably more plausible set of gene trees. This
allowed us to perform a genome-wide analysis of duplication and loss patterns on
the history of 63 eukaryote species, and predict ancestral gene content and order
for all ancestors along the phylogeny. AVAILABILITY: A web interface called
RefineTree, including ProfileNJ as well as a other gene tree correction methods,
which we also test on the Ensembl gene families, is available at: http://www
ens.iro.umontreal.ca/~adbit/polytomysolver.html. The code of ProfileNJ as well as
the set of gene trees corrected by ProfileNJ from Ensembl Compara version 73
families are also made available.
PMID- 27513925
TI - Equilibrium Dynamics of beta-N-Methylamino-L-Alanine (BMAA) and Its Carbamate
Adducts at Physiological Conditions.
AB - Elevated incidences of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia
complex (ALS/PDC) is associated with beta-methylamino-L-alanine (BMAA), a non
protein amino acid. In particular, the native Chamorro people living in the
island of Guam were exposed to BMAA by consuming a diet based on the cycad seeds.
Carbamylated forms of BMAA are glutamate analogues. The mechanism of
neurotoxicity of the BMAA is not completely understood, and BMAA acting as a
glutamate receptor agonist may lead to excitotoxicity that interferes with
glutamate transport systems. Though the interaction of BMAA with bicarbonate is
known to produce carbamate adducts, here we demonstrate that BMAA and its primary
and secondary adducts coexist in solution and undergoes a chemical exchange among
them. Furthermore, we determined the rates of formation/cleavage of the carbamate
adducts under equilibrium conditions using two-dimensional proton exchange NMR
spectroscopy (EXSY). The coexistence of the multiple forms of BMAA at
physiological conditions adds to the complexity of the mechanisms by which BMAA
functions as a neurotoxin.
PMID- 27513926
TI - Testing and Treating Women after Unsuccessful Conservative Treatments for
Overactive Bladder or Mixed Urinary Incontinence: A Model-Based Economic
Evaluation Based on the BUS Study.
AB - OBJECTIVE: To compare the cost-effectiveness of bladder ultrasonography, clinical
history, and urodynamic testing in guiding treatment decisions in a secondary
care setting for women failing first line conservative treatment for overactive
bladder or urgency-predominant mixed urinary incontinence. DESIGN: Model-based
economic evaluation from a UK National Health Service (NHS) perspective using
data from the Bladder Ultrasound Study (BUS) and secondary sources. METHODS: Cost
effectiveness analysis using a decision tree and a 5-year time horizon based on
the outcomes of cost per woman successfully treated and cost per Quality-Adjusted
Life-Year (QALY). Deterministic and probabilistic sensitivity analyses, and a
value of information analysis are also undertaken. RESULTS: Bladder
ultrasonography is more costly and less effective test-treat strategy than
clinical history and urodynamics. Treatment on the basis of clinical history
alone has an incremental cost-effectiveness ratio (ICER) of L491,100 per woman
successfully treated and an ICER of L60,200 per QALY compared with the treatment
of all women on the basis of urodynamics. Restricting the use of urodynamics to
women with a clinical history of mixed urinary incontinence only is the optimal
test-treat strategy on cost-effectiveness grounds with ICERs of L19,500 per woman
successfully treated and L12,700 per QALY compared with the treatment of all
women based upon urodynamics. Conclusions remained robust to sensitivity
analyses, but subject to large uncertainties. CONCLUSIONS: Treatment based upon
urodynamics can be seen as a cost-effective strategy, and particularly when
targeted at women with clinical history of mixed urinary incontinence only.
Further research is needed to resolve current decision uncertainty.
PMID- 27513927
TI - Measure, Then Show: Grasping Human Evolution Through an Inquiry-Based, Data
driven Hominin Skulls Lab.
AB - Incomprehension and denial of the theory of evolution among high school students
has been observed to also occur when teachers are not equipped to deliver a
compelling case also for human evolution based on fossil evidence. This paper
assesses the outcomes of a novel inquiry-based paleoanthropology lab teaching
human evolution to high-school students. The inquiry-based Be a
Paleoanthropologist for a Day lab placed a dozen hominin skulls into the hands of
high-school students. Upon measuring three variables of human evolution, students
explain what they have observed and discuss findings. In the 2013/14 school year,
11 biology classes in 7 schools in the Greater New Orleans area participated in
this lab. The interviewed teacher cohort unanimously agreed that the lab
featuring hominin skull replicas and stimulating student inquiry was a
pedagogically excellent method of delivering the subject of human evolution.
First, the lab's learning path of transforming facts to data, information to
knowledge, and knowledge to acceptance empowered students to themselves execute
part of the science that underpins our understanding of deep time hominin
evolution. Second, although challenging, the hands-on format of the lab was
accessible to high-school students, most of whom were readily able to engage the
lab's scientific process. Third, the lab's exciting and compelling pedagogy
unlocked higher order thinking skills, effectively activating the cognitive,
psychomotor and affected learning domains as defined in Bloom's taxonomy. Lastly,
the lab afforded students a formative experience with a high degree of retention
and epistemic depth. Further study is warranted to gauge the degree of these
effects.
PMID- 27513928
TI - Challenges to the Design of Clinical Trials for Live-Attenuated Tetravalent
Dengue Vaccines.
PMID- 27513929
TI - Serum-Based Quantification of MYCN Gene Amplification in Young Patients with
Neuroblastoma: Potential Utility as a Surrogate Biomarker for Neuroblastoma.
AB - We previously developed a method for determining MYCN gene amplification status
using cell-free DNA fragments released from cancer cells into the blood of
patients with neuroblastoma (NB). Here, we analyzed the relationship between MYCN
amplification (MNA) status and neuroblastoma prognosis. We screened serum samples
from 151 patients with NB for MNA, using real-time quantitative PCR, and compared
the results with MYCN status determined using paired tumor samples. We
additionally investigated whether MNA status correlates with patient survival.
When a cut-off value of 5 was used, serum-based MNA analysis was found to show
good sensitivity (86%) and very high specificity (95%). The sensitivities for
stage 1 and 2 might be acceptable, even though it is not as good as for stage 3
and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4). MNA status
correlated with overall survival in our cohort of 82 patients, with survival data
available (p < 0.01). The hazard ratio of MNA status was 4.98 in patients
diagnosed at less than 18 months of age (95% confidence interval, 1.00-24.78),
and 1.41 (95% confidence interval, 0.63-3.14) for those diagnosed at 18 months of
age or older. Serum-based MNA analysis is rapid and non-invasive compared with
tumor-based MNA analysis, and has potential to predict tumor MNA status. There is
still a room to improve the sensitivity of the test for tumors of stages 1 and 2,
nonetheless this assay might help to determine therapeutic strategies prior to
tumor biopsy, especially for patients with a life-threatening condition, as well
as for patients of less than 18 months of age whose risk-grouping and treatment
allocation depends on their MNA status.
PMID- 27513930
TI - Angiostrongylus cantonensis and A. malaysiensis Broadly Overlap in Thailand, Lao
PDR, Cambodia and Myanmar: A Molecular Survey of Larvae in Land Snails.
AB - Angiostrongylus cantonensis is a zoonotic nematode parasite causing human
eosinophilic meningitis (or meningoencephalitis) worldwide. A closely related
species, Angiostrongylus malaysiensis, might also be a human pathogen. Larvae
were obtained from land snails in Lao PDR, Cambodia, Myanmar and Thailand. We
sequenced two nuclear gene regions (nuclear ribosomal ITS2 and SSU rRNA) and a
portion of one mitochondrial gene (COI) from these larvae. Angiostrongylus
cantonensis and A. malaysiensis were identified. This is the first report of the
molecular identification of the two Angiostrongylus species in Lao PDR, Cambodia
and Myanmar. The regional distributions of the two species broadly overlap.
Phylogenetic relationships were inferred including data from Angiostrongylus
species deposited in public databases. All the gene regions we sequenced have
potential value in distinguishing between species of Angiostrongylus. The COI
gene exhibited the greatest intraspecific variation in the study region (five
haplotypes in A. cantonensis and four in A. malaysiensis) and might be suitable
for more detailed phylogeographic studies.
PMID- 27513931
TI - Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in
Patients with Rheumatoid Arthritis.
AB - BACKGROUND: Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases,
with genetic and environmental predisposition, and synovial angiogenesis is
considered to be a notable stage in its pathogenesis. Angiogenesis or vascular
proliferation has been suggested to be a pivotal mechanism involved in both
inflammation/immune activation and joint invasion and destruction. RA may be
considered an "angiogenic disease" because it is associated with active tissue
neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular
permeability, regulates angiogenesis, endothelial cell proliferation and
migration, chemotaxis, and capillary hyper permeability and therefore is involved
in the development of inflammation. VEGF is the most potent proangiogenic
molecule promoting the angiogenic phenotype of RA and is upregulated in RA.
OBJECTIVES: The aim of the study was to identify functional VEGF variants and
their possible association with VEGF expression, susceptibility to and severity
of RA. METHODS: 581 RA patients and of 341 healthy individuals were examined for
1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C
VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA
patients and controls were measured by ELISA. RESULTS: The -1154 A/G VEGF gene
polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs.
AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017,
respectively). VEGF -2578 A/C revealed differences in the case-control
distribution in codominant, recessive, dominant and overdominant models (all
p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with
susceptibility to RA in Polish population. The genotype-phenotype analysis showed
significant association between the VEGF -1154 A/G and -634 G/C and mean value of
the hemoglobin (all p = 0.05), additionally they relevated that the number of
women with the polymorphic allele -2578 C was lower than the number of women with
wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher
in RA patients than in control groups (both p = 0,0001). CONCLUSION: Present
findings indicated that VEGF genetic polymorphism as well as VEGF protein levels
may be associated with the susceptibility to RA in the Polish population.
PMID- 27513932
TI - Long Term Effects on Risk Factors for Cardiovascular Disease after 12-Months of
Aerobic Exercise Intervention - A Worksite RCT among Cleaners.
AB - OBJECTIVES: Occupational groups exposed to high occupational physical activity
have an increased risk for cardiovascular disease (CVD). This may be explained by
the high relative aerobic workload. Enhanced cardiorespiratory fitness reduces
the relative aerobic workload. Thus, the aim was to evaluate the 12-months
effects of worksite aerobic exercise on risk factors for CVD among cleaners.
METHODS: One hundred and sixteen cleaners aged 18-65 years were randomized to a
group performing aerobic exercise and a reference group receiving lectures.
Outcomes were collected at baseline and after 12-months. A repeated measures 2*2
multi-adjusted mixed-model design was applied to compare the between-group
differences using intention-to-treat analysis. RESULTS: Between-group differences
(p<0.05) were found favouring the aerobic exercise group: cardiorespiratory
fitness 2.15 (SE 1.03) mlO2/min/kg, aerobic workload -2.15 (SE 1.06) %HRR,
resting HR -5.31 (SE 1.61) beats/min, high sensitive C-reactive protein -0.65 (SE
0.24) MUg/ml. The blood pressure was unaltered. Stratified analyses on relative
aerobic workload at baseline revealed that those with relative aerobic workloads
>=30% of HRR seems to impose a notable adverse effect on resting and ambulatory
blood pressure. CONCLUSION: This long-term worksite aerobic exercise intervention
among cleaners led to several beneficial effects, but also potential adverse
effects among those with high relative aerobic workloads. TRIAL REGISTRATION:
Controlled-Trials.com ISRCTN86682076.
PMID- 27513933
TI - Live-Cell, Label-Free Identification of GABAergic and Non-GABAergic Neurons in
Primary Cortical Cultures Using Micropatterned Surface.
AB - Excitatory and inhibitory neurons have distinct roles in cortical dynamics. Here
we present a novel method for identifying inhibitory GABAergic neurons from non
GABAergic neurons, which are mostly excitatory glutamatergic neurons, in primary
cortical cultures. This was achieved using an asymmetrically designed
micropattern that directs an axonal process to the longest pathway. In the
current work, we first modified the micropattern geometry to improve cell
viability and then studied the axon length from 2 to 7 days in vitro (DIV). The
cell types of neurons were evaluated retrospectively based on immunoreactivity
against GAD67, a marker for inhibitory GABAergic neurons. We found that axons of
non-GABAergic neurons grow significantly longer than those of GABAergic neurons
in the early stages of development. The optimal threshold for identifying
GABAergic and non-GABAergic neurons was evaluated to be 110 MUm at 6 DIV. The
method does not require any fluorescence labelling and can be carried out on live
cells. The accuracy of identification was 98.2%. We confirmed that the high
accuracy was due to the use of a micropattern, which standardized the development
of cultured neurons. The method promises to be beneficial both for engineering
neuronal networks in vitro and for basic cellular neuroscience research.
PMID- 27513934
TI - Historical Biogeography of the Marine Snail Littorina saxatilis Inferred from
Haplotype and Shell Morphology Evolution in NW Spain.
AB - The marine snail Littorina saxatilis exhibits extreme morphological variation
between and within geographical regions and represents an excellent model for
assessing local adaptation. Previous studies support the hypothesis of parallel
evolution in sympatry of two morphologically different ecotypes (named as RB and
SU) that co-inhabit different habitats from Galician rocky shores (NW Spain), and
which are interrupted by sheltered areas inhabited by a different morph never
studied before (named as SRB). Here, we use morphological and mitochondrial DNA
(mtDNA) sequence data to test hypotheses on the origin and diversification of SRB
snails and to assess their evolutionary relationships with RB and SU ecotypes.
Our results show that the SRB morph displays the largest size and shell
elongation and the smallest relative shell aperture, representing an extreme type
of the RB vs. SU polymorphism, which has been linked to adaptation to sheltered
ecological factors. Phylogenetic analysis shows that the SRB morph shares
ancestry with RB and SU ecotypes, rejecting the hypothesis that the SRB morph
marks relict populations from which these ecotypes evolved in Galician coasts.
Our data support that genetic differentiation among SRB, RB and SU morphs results
from a general pattern of restricted gene flow and isolation by distance linked
to the colonization of Galician coasts by two independent mtDNA lineages, rather
than from a random fragmentation of the initial distributional range. Therefore,
the confinement of distinct lineages to specific geographical areas denote
evident limits to the distances these snails can disperse. Morphological analysis
indicates no association between mtDNA lineage and a specific morphotype, and
suggests the independent gain of convergent morphological patterns within each
mtDNA lineage in populations occupying contrasting habitats following the
colonization of Galician coasts.
PMID- 27513935
TI - Silica-Triggered Autoimmunity in Lupus-Prone Mice Blocked by Docosahexaenoic Acid
Consumption.
AB - Occupational exposure to respirable crystalline silica (cSiO2, quartz) is
etiologically linked to systemic lupus erythematosus (lupus) and other human
autoimmune diseases (ADs). In the female NZBWF1 mouse, a widely used animal model
that is genetically prone to lupus, short-term repeated intranasal exposure to
cSiO2 triggers premature initiation of autoimmune responses in the lungs and
kidneys. In contrast to cSiO2's triggering action, consumption of the omega-3
polyunsaturated fatty acid docosahexaenoic acid (DHA) prevents spontaneous onset
of autoimmunity in this mouse strain. The aim of this study was to test the
hypothesis that consumption of DHA will prevent cSiO2-triggered autoimmunity in
the female NZBWF1 mouse. Mice (6 wk old) were fed isocaloric AIN-93G diets
containing 0.0, 0.4, 1.2 or 2.4% DHA. Two wk after initiating feeding, mice were
intranasally instilled with 1 mg cSiO2 once per wk for 4 wk and maintained on
experimental diets for an additional 12 wk. Mice were then sacrificed and the
lung, blood and kidney assessed for markers of inflammation and autoimmunity. DHA
was incorporated into lung, red blood cells and kidney from diet in a
concentration-dependent fashion. Dietary DHA dose-dependently suppressed cSiO2
triggered perivascular leukocyte infiltration and ectopic lymphoid tissue
neogenesis in the lung. DHA consumption concurrently inhibited cSiO2-driven
elevation of proinflammatory cytokines, B-cell proliferation factors, IgG and
anti-dsDNA Ig in both bronchoalveolar lavage fluid and plasma. DHA's prophylactic
effects were further mirrored in reduced proteinuria and glomerulonephritis in
cSiO2-treated mice. Taken together, these results reveal that DHA consumption
suppresses cSiO2 triggering of autoimmunity in female NZBWF1 mice as manifested
in the lung, blood and kidney. Our findings provide novel insight into how
dietary modulation of the lipidome might be used to prevent or delay triggering
of AD by cSiO2. Such knowledge opens the possibility of developing practical, low
cost preventative strategies to reduce the risk of initiating AD and subsequent
flaring in cSiO2-exposed individuals. Additional research in this model is
required to establish the mechanisms by which DHA suppresses cSiO2-induced
autoimmunity and to ascertain unique lipidome signatures predictive of
susceptibility to cSiO2-triggered AD.
PMID- 27513936
TI - Successful Treatment of Relapsing Bowen's Disease with Ingenol Mebutate: The Use
of Dermoscopy to Monitor the Therapeutic Response.
AB - Ingenol mebutate (IM) has recently been approved for the topical treatment of
actinic keratoses. It appears to have a dual mechanism of action: rapid necrosis
after gel application and a subsequent immune-mediated response, which targets
any residual dysplastic epidermal cells. We report the successful treatment of a
woman, who had been relapsing into Bowen's disease (BD) on her right forefinger
for 8 years. During her clinical history, she had received an allogeneic, HLA
identical stem cell transplant for myeloproliferative syndrome with a JAK2V617F
mutation and lobectomy of the pulmonary right lower lobe for adenocarcinoma. We
used dermoscopy to monitor the therapeutic response of BD. We discuss IM gel as a
possible therapeutic option for BD.
PMID- 27513937
TI - Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid
Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers,
Melatonin and Dopamine, for Brain Monoamine Neurotransmitters.
AB - BACKGROUND: Phenylketonuria (PKU) is due to a defective hepatic enzyme,
phenylalanine (Phe) hydroxylase. Transport of the precursor amino acids from
blood into the brain for serotonin and dopamine synthesis is reported to be
inhibited by high blood Phe concentrations. Deficiencies of serotonin and
dopamine are involved in neurocognitive dysfunction in PKU. OBJECTIVE: (1) To
evaluate the effects of sapropterin (BH4) and concurrent use of large neutral
amino acids (LNAA) on the peripheral biomarkers, melatonin and dopamine with the
hypothesis they reflect brain serotonin and dopamine metabolism. (2) To evaluate
synergistic effects with BH4 and LNAA. (3) To determine the effects of blood Phe
concentrations on the peripheral biomarkers concentrations. METHODS: Nine adults
with PKU completed our study consisting of four 4-week phases: (1) LNAA
supplementation, (2) Washout, (3) BH4 therapy, and (4) LNAA with BH4 therapy. An
overnight protocol measured plasma amino acids, serum melatonin, and 6
sulfatoxymelatonin and dopamine in first void urine after each phase. RESULTS:
(1) Three out of nine subjects responded to BH4. A significant increase of serum
melatonin levels was observed in BH4 responders with decreased blood Phe
concentration. No significant change in melatonin, dopamine or Phe levels was
observed with BH4 in the subjects as a whole. (2) Synergistic effects with BH4
and LNAA were observed in serum melatonin in BH4 responders. (3) The relationship
between serum melatonin and Phe showed a significant negative slope (p = 0.0005)
with a trend toward differing slopes among individual subjects (p = 0.066). There
was also a negative association overall between blood Phe and urine 6
sulfatoxymelatonin and dopamine (P = 0.040 and 0.047). CONCLUSION: Blood Phe
concentrations affected peripheral monoamine neurotransmitter biomarker
concentrations differently in each individual with PKU. Melatonin levels
increased with BH4 therapy only when blood Phe decreased. Monitoring peripheral
neurotransmitter metabolites may assist in optimizing individualized treatment in
PKU.
PMID- 27513938
TI - Outcomes in Patients with Vestibular Schwannoma after Subtotal Resection and
Adjuvant Radiosurgery.
AB - BACKGROUND: The debate continues with a limited number of publications describing
outcomes in patients with vestibular schwannoma (VS) treated with planned
subtotal resection (STR) plus stereotactic radiosurgery (SRS). Here we present
our experience. METHODS: This is a retrospective review of 22 patients with VS
Koos grade III and IV who were treated with STR followed by SRS. Tumor volumes,
facial nerve function, hearing preservation, and the presence of trigeminal
neuropathy were noted. Spearman's rank test was used to correlate facial nerve
grade with postoperative tumor residual tumor volume. RESULTS: Tumor control was
achieved in all patients with a mean follow-up of 28 months. No patient required
other treatment beyond the original surgery and adjuvant SRS during this period.
After a mean postoperative period of 28 months, 19/22 patients had excellent
(House-Brackmann I or II) facial nerve function grading. Improved facial nerve
function was positively correlated with larger residual tumor volume (rs = 0.63).
Kaplan-Meier curve showed around 80% probability for regaining facial nerve
function after initial deterioration. Four patients reported postoperative facial
numbness at the side of surgery, with 3 cases showing improvement within a month.
Temporary postoperative caudal cranial nerve dysfunction was observed in 2
patients. CONCLUSION: Hybrid strategy of STR and adjuvant SRS provides patients
with large VS excellent tumor control and a good clinical outcome.
PMID- 27513939
TI - Sources and Dynamics of Inorganic Carbon within the Upper Reaches of the Xi River
Basin, Southwest China.
AB - The carbon isotopic composition (delta13C) of dissolved and particulate inorganic
carbon (DIC; PIC) was used to compare and analyze the origin, dynamics and
evolution of inorganic carbon in two headwater tributaries of the Xi River,
Southwest China. Carbonate dissolution and soil CO2 were regarded as the primary
sources of DIC on the basis of delta13CDIC values which varied along the Nanpan
and Beipan Rivers, from -13.90/00 to 8.10/00. Spatial trends in DIC differed
between the two rivers (i.e., the tributaries), in part because factors
controlling pCO2, which strongly affected carbonate dissolution, differed between
the two river basins. Transport of soil CO2 and organic carbon through hydrologic
conduits predominately controlled the levels of pCO2 in the Nanpan River.
However, pCO2 along the upper reaches of the Nanpan River also was controlled by
the extent of urbanization and industrialization relative to agriculture. DIC
concentrations in the highly urbanized upper reaches of the Nanpan River were
typical higher than in other carbonate-dominated areas of the upper Xi River.
Within the Beipan River, the oxidation of organic carbon is the primary process
that maintains pCO2 levels. The pCO2 within the Beipan River was more affected by
sulfuric acid from coal industries, inputs from a scenic spot, and groundwater
than along the Nanpan River. With regards to PIC, the contents and delta13C
values in the Nanpan River were generally lower than those in the Beipan River,
indicating that chemical and physical weathering contributes more marine
carbonate detritus to the PIC along the Beipan River. The CO2 evasion flux from
the Nanpan River was higher than that in the Beipan River, and generally higher
than along the middle and lower reaches of the Xi River, demonstrating that the
Nanpan River is an important net source of atmospheric CO2 in Southwest China.
PMID- 27513940
TI - Self-Reported Adherence to Trifluridine and Tipiracil Hydrochloride for
Metastatic Colorectal Cancer: A Retrospective Cohort Study.
AB - BACKGROUND: A novel oral agent that consists of trifluridine and tipiracil
hydrochloride (TFTD) has been established as salvage-line treatment for
metastatic colorectal cancer (mCRC). Adherence to TFTD is crucial to maintaining
appropriate curative effects. This study sought to clarify adherence to TFTD and
identify candidate factors deteriorating adherence at our institution. METHODS: A
total of 50 consecutive mCRC patients who received TFTD monotherapy between June
1, 2014 and July 31, 2015 were analyzed in this study. Adherence to TFTD was
checked by pharmacists using a self-reported treatment diary and interviewing
nonadherents at a pharmaceutical outpatient clinic. The adherence rate was
defined as the number of patient intakes per 20 scheduled intakes in one cycle.
We retrospectively surveyed the factors from the electronic patient record
associated with reduced adherence. We measured relative dose intensity, defined
as the dose intensity divided by the initial dose (each in milligrams per square
meter per week). RESULTS: Patient characteristics were as follows: males/females,
20/30; median age, 61 years (range, 34-83 years); performance status 0/1, 37/13.
Median relative dose intensity of TFTD was 91.0%. Adherence rates were 95.0% for
the first cycle of TFTD, 97.3% for the second cycle, 98.0% for the third cycle,
and 98.2% for the fourth cycle. Factors associated with deteriorated adherence to
TFTD were nausea/vomiting/decreased appetite (27.1%, 23 instances), pain (25.9%,
22 instances), neutropenia (11.8%, 10 instances), and missed dose (4.7%, 4
instances). Increased nonadherence to TFTD was associated with Eastern
Cooperative Oncology Group performance status 1, while increased TFTD adherence
in the first cycle was associated with prior regimens >=4. CONCLUSIONS: The high
frequency of treatment-related gastrointestinal disorder is the main factor
affecting adherence to TFTD. Intensive supportive care in the management of these
symptoms could assist adequate adherence to TFTD in mCRC patients.
PMID- 27513941
TI - The Etiology, Incidence, and Impact of Preservation Fluid Contamination during
Liver Transplantation.
AB - The role of contaminated preservation fluid in the development of infection after
liver transplantation has not been fully elucidated. To assess the incidence and
etiology of contaminated preservation fluid and determine its impact on the
subsequent development of infection after liver transplantation, we prospectively
studied 50 consecutive liver transplants, and cultured the following samples in
each instance: preservation fluid (immediately before and at the end of the back
table procedure, and just before implantation), blood, and bile from the donor,
and ascitic fluid from the recipient. When any culture was positive, blood
cultures were obtained and targeted antimicrobial therapy was started. We found
that the incidence of contaminated preservation fluid was 92% (46 of 50 cases of
liver transplantation per year), but only 28% (14/50) were contaminated by
recognized pathogens. Blood and bile cultures from the donor were positive in 28%
and 6% respectively, whereas ascitic fluid was positive in 22%. The most
frequently isolated microorganisms were coagulase-negative staphylococci. In nine
cases, the microorganisms isolated from the preservation fluid concurred with
those grown from the donor blood cultures, and in one case, the isolate matched
with the one obtained from bile culture. No liver transplant recipient developed
an infection due to the transmission of an organism isolated from the
preservation fluid. Our findings indicate that contamination of the preservation
fluid is frequent in liver transplantation, and it is mainly caused by
saprophytic skin flora. Transmission of infection is low, particularly among
those recipients given targeted antimicrobial treatment for organisms isolated in
the preservation fluid.
PMID- 27513942
TI - Denervation-Induced Activation of the Ubiquitin-Proteasome System Reduces
Skeletal Muscle Quantity Not Quality.
AB - It is well known that the ubiquitin-proteasome system is activated in response to
skeletal muscle wasting and functions to degrade contractile proteins. The loss
of these proteins inevitably reduces skeletal muscle size (i.e., quantity).
However, it is currently unknown whether activation of this pathway also affects
function by impairing the muscle's intrinsic ability to produce force (i.e.,
quality). Therefore, the purpose of this study was twofold, (1) document how the
ubiquitin-proteasome system responds to denervation and (2) identify the
physiological consequences of these changes. To induce soleus muscle atrophy,
C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14
days (n = 6-8 per group). At these time points, content of several proteins
within the ubiquitin-proteasome system were determined via Western blot, while ex
vivo whole muscle contractility was specifically analyzed at day 14. Denervation
temporarily increased several key proteins within the ubiquitin-proteasome
system, including the E3 ligase MuRF1 and the proteasome subunits 19S, alpha7 and
beta5. These changes were accompanied by reductions in absolute peak force and
power, which were offset when expressed relative to physiological cross-sectional
area. Contrary to peak force, absolute and relative forces at submaximal
stimulation frequencies were significantly greater following 14 days of
denervation. Taken together, these data represent two keys findings. First,
activation of the ubiquitin-proteasome system is associated with reductions in
skeletal muscle quantity rather than quality. Second, shortly after denervation,
it appears the muscle remodels to compensate for the loss of neural activity via
changes in Ca2+ handling.
PMID- 27513943
TI - Maternal Plasma Nerve Growth Factor at the 11+0-13+6 Weeks' Scan as a Potential
Angiogenic Marker of Preeclampsia: A Pilot Study.
AB - OBJECTIVE: The aim of this study was to determine the role of nerve growth factor
(NGF) in the first-trimester screening for preeclampsia (PE). METHODS: Uterine
artery Doppler (UtAD) was determined transvaginally. Maternal concentrations of
NGF were assessed in 42 patients who subsequently developed PE and in 95
controls. Quantile and multivariate regression analyses were performed for the
NGF and UtAD adjustment and expressed as the multiple of the median (MoM) of the
unaffected group. Logistic regression analysis was conducted to identify the best
model for the prediction of PE. RESULTS: The maternal plasma concentration of NGF
exhibited a trend towards lower values in patients who subsequently developed
early-onset PE (e-PE) compared to controls (10.7 vs. 38.2 pg/ml, respectively; p
= not significant). The median MoM NGF in the all-PE, e-PE and control groups was
0.97 (95% CI 0.13-3.36), 0.62 (95% CI 0.16-2.19) and 1.00 (95% CI 0.20-2.94),
respectively (p = not significant). The best predictors of PE were previous PE,
chronic hypertension and UtAD. With a false-positive rate of 10%, the detection
rates (DRs) of all-PE and e-PE were 38 and 50%, respectively. The addition of MoM
NGF did not improve the DR of PE. CONCLUSION: First-trimester NGF tends to be
lower in patients who subsequently develop e-PE.
PMID- 27513944
TI - Influence of physicochemical parameters and high pressure processing on the
volatile compounds of Serrano dry-cured ham after prolonged refrigerated storage.
AB - One hundred and three volatile compounds were detected by solid-phase
microextraction followed by gas chromatography-mass spectrometry in 30 ripened
Serrano dry-cured hams, submitted or not to high pressure processing (HPP) and
afterwards held for 5months at 4 degrees C. The effect of ham physicochemical
parameters and HPP (600MPa for 6min) on volatile compounds was assessed.
Physicochemical parameters primarily affected the levels of acids, alcohols,
alkanes, esters, benzene compounds, sulfur compounds and some miscellaneous
compounds. Intramuscular fat content was the physicochemical parameter with the
most pronounced effect on the volatile fraction of untreated Serrano ham after
refrigerated storage, influencing the levels of 38 volatile compounds while aw,
salt content and salt-in-lean ratio respectively influenced the levels of 4, 4
and 5 volatile compounds. HPP treatment affected 21 volatile compounds, resulting
in higher levels of alkanes and ketones and lower levels of esters and secondary
alcohols, what might affect Serrano ham odor and aroma after 5months of
refrigerated storage.
PMID- 27513945
TI - Application of quantitative magnetization transfer magnetic resonance imaging for
characterization of dry-cured hams.
AB - Quantitative magnetization transfer magnetic resonance imaging (qMT-MRI) was
employed to characterize dry-cured ham tissues differing in anatomical positions
and processing protocols. Experimentally obtained MR images of dry-cured ham
sections were analyzed by the well-established binary-spin-bath (BSB) model. The
model enabled an efficient discrimination between a free-water proton pool and a
restricted-macromolecular proton pool. Significant differences in restricted pool
sizes were found among different ham sections. Values of the restricted pool size
obtained by the model were in a good agreement with chemically determined protein
content. The study confirmed the feasibility of the applied qMT-MRI as a
nondestructive tool for characterization of dry-cured ham tissues.
PMID- 27513946
TI - Evolutionary Games of Multiplayer Cooperation on Graphs.
AB - There has been much interest in studying evolutionary games in structured
populations, often modeled as graphs. However, most analytical results so far
have only been obtained for two-player or linear games, while the study of more
complex multiplayer games has been usually tackled by computer simulations. Here
we investigate evolutionary multiplayer games on graphs updated with a Moran
death-Birth process. For cycles, we obtain an exact analytical condition for
cooperation to be favored by natural selection, given in terms of the payoffs of
the game and a set of structure coefficients. For regular graphs of degree three
and larger, we estimate this condition using a combination of pair approximation
and diffusion approximation. For a large class of cooperation games, our
approximations suggest that graph-structured populations are stronger promoters
of cooperation than populations lacking spatial structure. Computer simulations
validate our analytical approximations for random regular graphs and cycles, but
show systematic differences for graphs with many loops such as lattices. In
particular, our simulation results show that these kinds of graphs can even lead
to more stringent conditions for the evolution of cooperation than well-mixed
populations. Overall, we provide evidence suggesting that the complexity arising
from many-player interactions and spatial structure can be captured by pair
approximation in the case of random graphs, but that it need to be handled with
care for graphs with high clustering.
PMID- 27513947
TI - The Sulfamate Small Molecule CAIX Inhibitor S4 Modulates Doxorubicin Efficacy.
AB - Carbonic anhydrase IX (CAIX) is a tumor-specific protein that is upregulated
during hypoxic conditions where it is involved in maintaining the pH balance.
CAIX causes extracellular acidification, thereby limiting the uptake of weak
basic chemotherapeutic agents, such as doxorubicin, and decreasing its efficacy.
The aim of this study was to determine if doxorubicin efficacy can be increased
when combined with the selective sulfamate CAIX inhibitor S4. The effect of S4 on
doxorubicin efficacy was tested in vitro using cell viability assays with MDA-MB
231, FaDu, HT29 -CAIX high and HT29 -CAIX low cell lines. In addition, the
efficacy of this combination therapy was investigated in tumor xenografts of the
same cell lines. The addition of S4 in vitro increased the efficacy of
doxorubicin in the MDA-MB-231 during hypoxic exposure (IC50 is 0.25 versus 0.14
uM, p = 0.0003). Similar results were observed for HT29-CAIX high with S4 during
normoxia (IC50 is 0.20 versus 0.08 uM, p<0.0001) and in the HT29 -CAIX low cells
(IC50 is 0.09 uM, p<0.0001). In vivo doxorubicin treatment was only effective in
the MDA-MB-231 xenografts, but the efficacy of doxorubicin was decreased when
combined with S4. In conclusion, the efficacy of doxorubicin treatment can be
increased when combined with the selective sulfamate CAIX inhibitor S4 in vitro
in certain cell lines. Nevertheless, in xenografts S4 did not enhance doxorubicin
efficacy in the FaDu and HT29 tumor models and decreased doxorubicin efficacy in
the MDA-MB-231 tumor model. These results stress the importance of better
understanding the role of CAIX inhibitors in intratumoral pH regulation before
combining them with standard treatment modalities, such as doxorubicin.
PMID- 27513948
TI - Impact of cyclometalated ruthenium(II) complexes on lactate dehydrogenase
activity and cytotoxicity in gastric and colon cancer cells.
AB - Lactate dehydrogenase (LDH) is a redox enzyme often overexpressed in cancer cells
allowing their survival in stressful metabolic tumor environment. Ruthenium(II)
complexes have been shown to impact on the activity of purified horseradish
peroxidase and glucose oxidase but the physiological relevance remains unclear.
In this study we investigated how ruthenium complexes impact on the activity of
LDH in vitro and in cancer cells and performed a comparative study using
polypyridine ruthenium(II) complex [Ru(bpy)3]2+ (1) and its structurally related
cyclometalated 2-phenylpyridinato counterpart [Ru(phpy)(bpy)2]+ (2) (bpy=2,2'
bipyridine, phpyH=2-phenylpyridine). We show that the cytotoxicity in gastric and
colon cancer cells induced by 2 is significantly higher compared to 1. The
kinetic inhibition mechanisms on purified LDH and the corresponding inhibition
constants Ki or i0.5 values were calculated. Though complexes 1 and 2 are
structurally very similar (one Ru-C bond in 2 replaces one Ru-N bond in 1), their
inhibition modes are different. Cyclometalated complex 2 behaves exclusively as a
non-competitive inhibitor of LDH from rabbit muscle (LDHrm), strongly suggesting
that 2 does not interact with LDH in the vicinities of either lactate/pyruvate or
NAD+/NADH binding sites. Sites of interaction of 1 and 2 with LDHrm were revealed
theoretically through computational molecular docking. Inhibition of LDH activity
by 2 was confirmed in cancer cells. Altogether, these results revealed an
inhibition of LDH activity by ruthenium complex through a direct interaction
structurally tuned by a Ru-C bond.
PMID- 27513949
TI - Visible light-induced formation of corrole-manganese(V)-oxo complexes:
Observation of multiple oxidation pathways.
AB - Two manganese(V)-oxo corroles [MnV(Cor)O] that differ in their electronic
environments were produced by visible light irradiation of highly photo-labile
corrole-manganese(IV) bromates. The corrole ligands under study include 5,10,15
tris(pentafluorophenyl)corrole (TPFC), and 5,10,15-triphenylcorrole (TPC). The
kinetics of oxygen transfer atom (OAT) reactions with various organic reductants
by these photo-generated MnV(Cor)O were also studied in CH3CN and CH2Cl2
solutions. MnV(Cor)O exhibits remarkable solvent and ligand effect on its
reactivity and spectral behavior. In the more electron-deficient TPFC system and
in the polar solvent CH3CN, MnV(Cor)O returned MnIII corrole in the end of
oxidation reactions. However, in the less polar solvent CH2Cl2 or in the less
electron-deficient TPC system, MnIV product was formed instead of MnIII.
Furthermore, with the same substrates and in the same solvent, the order of
reactivity of MnV(Cor)O was TPC>TPFC, which is inverted from that expected based
on the electron-demand of corrole ligands. Our spectral and kinetic results in
this study provide compelling evidence in favor of multiple oxidation pathways,
where MnV(Cor)O may serve as direct two-electron oxidant or undergo a
disproportionation reaction to form a manganese(VI)-oxo corrole as the true
oxidant. The choice of pathways is strongly dependent on the nature of the
solvent and the corrole ligand.
PMID- 27513950
TI - Auditory Stimuli Coding by Postsynaptic Potential and Local Field Potential
Features.
AB - The relation between physical stimuli and neurophysiological responses, such as
action potentials (spikes) and Local Field Potentials (LFP), has recently been
experimented in order to explain how neurons encode auditory information.
However, none of these experiments presented analyses with postsynaptic
potentials (PSPs). In the present study, we have estimated information values
between auditory stimuli and amplitudes/latencies of PSPs and LFPs in
anesthetized rats in vivo. To obtain these values, a new method of information
estimation was used. This method produced more accurate estimates than those
obtained by using the traditional binning method; a fact that was corroborated by
simulated data. The traditional binning method could not certainly impart such
accuracy even when adjusted by quadratic extrapolation. We found that the
information obtained from LFP amplitude variation was significantly greater than
the information obtained from PSP amplitude variation. This confirms the fact
that LFP reflects the action of many PSPs. Results have shown that the auditory
cortex codes more information of stimuli frequency with slow oscillations in
groups of neurons than it does with slow oscillations in neurons separately.
PMID- 27513951
TI - Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations,
Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in
Vietnam.
AB - Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described
cause of morbidity and mortality in children and HIV-infected adults in sub
Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS
disease in Asia are not well documented. We retrospectively identified >100 cases
of iNTS infections in an infectious disease hospital in Southern Vietnam between
2008 and 2013. Clinical records were accessed to evaluate demographic and
clinical factors associated with iNTS infection and to identify risk factors
associated with death. Multi-locus sequence typing and antimicrobial
susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71%
were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous
drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection
was significantly associated with death (p = 0.039). S. Enteritidis (Sequence
Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89)
were the most commonly identified serovars; S. Typhimurium was significantly more
common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected
patients were more likely to exhibit reduced susceptibility against trimethoprim
sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS
disease is a severe infection in Vietnam with a high mortality rate. As in sub
Saharan Africa, HIV infection was a risk factor for death, with the majority of
the burden in this population found in HIV-infected adult men.
PMID- 27513952
TI - Comparative Digital Gene Expression Analysis of the Arabidopsis Response to
Volatiles Emitted by Bacillus amyloliquefaciens.
AB - Some plant growth-promoting rhizobacteria (PGPR) regulated plant growth and
elicited plant basal immunity by volatiles. The response mechanism to the
Bacillus amyloliquefaciens volatiles in plant has not been well studied. We
conducted global gene expression profiling in Arabidopsis after treatment with
Bacillus amyloliquefaciens FZB42 volatiles by Illumina Digital Gene Expression
(DGE) profiling of different growth stages (seedling and mature) and tissues
(leaves and roots). Compared with the control, 1,507 and 820 differentially
expressed genes (DEGs) were identified in leaves and roots at the seedling stage,
respectively, while 1,512 and 367 DEGs were identified in leaves and roots at the
mature stage. Seventeen genes with different regulatory patterns were validated
using quantitative RT-PCR. Numerous DEGs were enriched for plant hormones, cell
wall modifications, and protection against stress situations, which suggests that
volatiles have effects on plant growth and immunity. Moreover, analyzes of
transcriptome difference in tissues and growth stage using DGE profiling showed
that the plant response might be tissue-specific and/or growth stage-specific.
Thus, genes encoding flavonoid biosynthesis were downregulated in leaves and
upregulated in roots, thereby indicating tissue-specific responses to volatiles.
Genes related to photosynthesis were downregulated at the seedling stage and
upregulated at the mature stage, respectively, thereby suggesting growth period
specific responses. In addition, the emission of bacterial volatiles
significantly induced killing of cells of other organism pathway with up
regulated genes in leaves and the other three pathways (defense response to
nematode, cell morphogenesis involved in differentiation and trichoblast
differentiation) with up-regulated genes were significantly enriched in roots.
Interestingly, some important alterations in the expression of growth-related
genes, metabolic pathways, defense response to biotic stress and hormone-related
genes were firstly founded response to FZB42 volatiles.
PMID- 27513953
TI - Postpartum Loss to HIV Care and HIV Viral Suppression among Previously Diagnosed
HIV-Infected Women with a Live Birth in New York State.
AB - Mother-to-child-transmission of HIV in the United States has been greatly
reduced, with clear benefits for the child. However, little is known about
factors that predict maternal loss to HIV care in the postpartum year. This
retrospective cohort study included 980 HIV-positive women, diagnosed with HIV at
least one year before pregnancy, who had a live birth during 2008-2010 in New
York State. Women who did not meet the following criterion in the 12 months after
the delivery-related hospital discharge were considered to be lost to HIV care:
two or more laboratory tests (CD4 or HIV viral load), separated by at least 90
days. Adjusted relative risks (aRR) and 95% confidence intervals (CI) for
predictors of postpartum loss to HIV care were identified with Poisson
regression, solved using generalized estimating equations. Having an unsuppressed
(>200 copies/mL) HIV viral load in the postpartum year was also evaluated.
Overall, 24% of women were loss to HIV care during the postpartum year. Women
with low participation in HIV care during preconception were more likely to be
lost to HIV care during the postpartum year (aRR: 2.70; 95% CI: 2.09-3.49). In
contrast, having a low birth weight infant was significantly associated with a
decreased likelihood of loss to HIV care (aRR: 0.72; 95% CI: 0.53-0.98). While
75% of women were virally suppressed at the last viral load before delivery only
44% were continuously suppressed in the postpartum year; 12% had no viral load
test reported in the postpartum year and 44% had at least one unsuppressed viral
load test. Lack of engagement in preconception HIV-related health care predicts
postpartum loss to HIV care for HIV-positive parturient women. Many women had
poor viral control during the postpartum period, increasing the risk of disease
progression and infectivity.
PMID- 27513954
TI - Laguerre Filter Analysis with Partial Least Square Regression Reveals a Priming
Effect of ERK and CREB on c-FOS Induction.
AB - Signaling networks are made up of limited numbers of molecules and yet can code
information that controls different cellular states through temporal patterns and
a combination of signaling molecules. In this study, we used a data-driven
modeling approach, the Laguerre filter with partial least square regression, to
describe how temporal and combinatorial patterns of signaling molecules are
decoded by their downstream targets. The Laguerre filter is a time series model
used to represent a nonlinear system based on Volterra series expansion.
Furthermore, with this approach, each component of the Volterra series expansion
is expanded by Laguerre basis functions. We combined two approaches, application
of a Laguerre filter and partial least squares (PLS) regression, and applied the
combined approach to analysis of a signal transduction network. We applied the
Laguerre filter with PLS regression to identify input and output (IO)
relationships between MAP kinases and the products of immediate early genes
(IEGs). We found that Laguerre filter with PLS regression performs better than
Laguerre filter with ordinary regression for the reproduction of a time series of
IEGs. Analysis of the nonlinear characteristics extracted using the Laguerre
filter revealed a priming effect of ERK and CREB on c-FOS induction.
Specifically, we found that the effects of a first pulse of ERK enhance the
subsequent effects on c-FOS induction of treatment with a second pulse of ERK, a
finding consistent with prior molecular biological knowledge. The variable
importance of projections and output loadings in PLS regression predicted the
upstream dependency of each IEG. Thus, a Laguerre filter with partial least
square regression approach appears to be a powerful method to find the processing
mechanism of temporal patterns and combination of signaling molecules by their
downstream gene expression.
PMID- 27513955
TI - Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A
Role for B Cell-Activating Factor.
AB - BACKGROUND: B cells, key cells in allergic inflammation, differentiate in the
bone marrow and their precursors include pro-B, pre-B and immature B cells.
Eosinophil progenitor cells increase in the lung after allergen exposure.
However, the existence and possible role of B cell precursors in the lung during
allergic inflammation remains elusive. METHODS: A BALB/c mouse model of allergic
airway inflammation was utilized to perform phenotypic and quantification
analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell
maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors
(CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and
serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p.
administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell
assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of
asthmatic patients and healthy controls. RESULTS: Precursor pro and pre-B cells
increase in the lung after allergen exposure, proliferate in the lung tissue in
vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40,
CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors
for BAFF at baseline, while after allergen challenge both their ligand BAFF and
the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in
the lung in vivo decreases eosinophils and proliferating precursor B cells.
Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation
units. BAFF is increased in the BAL of severe asthmatics. CONCLUSION: Our data
support the concept of a BAFF-mediated role for B cell precursors in allergic
airway inflammation.
PMID- 27513956
TI - RNase activity of sialic acid-binding lectin from bullfrog eggs drives antitumor
effect via the activation of p38 MAPK to caspase-3/7 signaling pathway in human
breast cancer cells.
AB - Sialic acid-binding lectin obtained from bullfrog eggs (SBL) induces cell death
in cancer cells but not in normal cells. This antitumor effect is mediated
through its ribonuclease (RNase) activity. However, the underlying molecular
mechanisms remain unclear. We found that the p38 mitogen-activated protein kinase
(MAPK) signaling pathway was activated when SBL induced cell death in three human
breast cancer cell lines: SK-BR-3, MCF-7, and MDA-MB231. The suppression of p38
MAPK phosphorylation by a p38 MAPK inhibitor as well as short interference RNA
knockdown of p38 MAPK expression significantly decreased cell death and increased
the cell viability of SBL-treated MDA-MB231 cells. H103A, an SBL mutant lacking
in RNase activity, showed decreased SBL-induced cell death compared with native
SBL. However, the loss of RNase activity of SBL had no effect on its
internalization into cells. The H103A mutant also displayed decreased
phosphorylation of p38 MAPK. Moreover, SBL promoted caspase-3/7 activation
followed by a cleavage of poly (ADP-ribose)-polymerase, whereas the SBL mutant,
H103A, lost this ability. The SBL-induced caspase-3/7 activation was suppressed
by the p38 MAPK inhibitor, SB203580, as well as pan-caspase inhibitor, zVAD-fmk.
In the presence of zVAD-fmk, the SBL-induced cell death was decreased. In
addition, the cell viability of SBL-treated MDA-MB231 cells recovered by zVAD-fmk
treatment. Taken together, our results suggest that the RNase activity of SBL
leads to breast cancer cell death through the activation of p38 MAPK followed by
the activation of caspase-3/7.
PMID- 27513957
TI - Bowenoid Actinic Keratosis and Bowen's Disease Treated Successfully with Ingenol
Mebutate.
AB - Ingenol mebutate (IM) is a topical pharmacotherapy approved in Switzerland since
2012 for treating non-hypertrophic, non-hyperkeratotic actinic keratosis (AK). We
report 2 cases with off-label use of IM. The first case of bowenoid AK was
treated with 150 MUg IM for 3 consecutive days with an almost complete clinical
remission of the lesion. The second case of Bowen's disease was treated with 500
MUg IM for 2 consecutive days leading to complete clinical remission.
PMID- 27513958
TI - Flow Scales of Influence on the Settling Velocities of Particles with Varying
Characteristics.
AB - The settling velocities of natural, synthetic, and industrial particles were
measured in a grid turbulence facility using optical measurement techniques.
Particle image velocimetry and 2D particle tracking were used to measure the
instantaneous velocities of the flow and the particles' trajectories
simultaneously. We find that for particles examined in this study (Rep = 0.4
123), settling velocity is either enhanced or unchanged relative to stagnant flow
for the range of investigated turbulence conditions. The smallest particles'
normalized settling velocities exhibited the most consistent trends when plotted
versus the Kolmogorov-based Stokes numbers suggesting that the dissipative scales
influence their dynamics. In contrast, the mid-sized particles were better
characterized with a Stokes number based on the integral time scale. The largest
particles were largely unaffected by the flow conditions. Using proper orthogonal
decomposition (POD), the flow pattern scales are compared to particle trajectory
curvature to complement results obtained through dimensional analysis using
Stokes numbers. The smallest particles are found to have trajectories with
curvatures of similar scale as the small flow scales (higher POD modes) whilst
mid-sized particle trajectories had curvatures that were similar to the larger
flow patterns (lower POD modes). The curvature trajectories of the largest
particles did not correspond to any particular flow pattern scale suggesting that
their trajectories were more random. These results provide experimental evidence
of the "fast tracking" theory of settling velocity enhancement in turbulence and
demonstrate that particles align themselves with flow scales in proportion to
their size.
PMID- 27513959
TI - Carbonic Anhydrases in Cnidarians: Novel Perspectives from the Octocorallian
Corallium rubrum.
AB - Although the ability to elaborate calcium carbonate biominerals was apparently
gained independently during animal evolution, members of the alpha carbonic
anhydrases (alpha-CAs) family, which catalyze the interconversion of CO2 into
HCO3-, are involved in the biomineralization process across metazoans. In the
Mediterranean red coral Corallium rubrum, inhibition studies suggest an essential
role of CAs in the synthesis of two biominerals produced in this octocoral, the
axial skeleton and the sclerites. Hitherto no molecular characterization of these
enzymes was available. In the present study we determined the complete set of
alpha-CAs in C. rubrum by data mining the genome and transcriptome, and measured
their differential gene expression between calcifying and non-calcifying tissues.
We identified six isozymes (CruCA1-6), one cytosolic and five secreted/membrane
bound among which one lacked two of the three zinc-binding histidines and was so
referred to as a carbonic anhydrase related protein (CARP). One secreted isozyme
(CruCA4) showed specific expression both by qPCR and western-blot in the
calcifying tissues, suggesting its involvement in biomineralization. Moreover,
phylogenetic analyses of alpha-CAs, identified in six representative cnidarians
with complete genome, support an independent recruitment of alpha-CAs for
biomineralization within anthozoans. Finally, characterization of cnidarian CARPs
highlighted two families: the monophyletic cytosolic CARPs, and the polyphyletic
secreted CARPs harboring a cnidarian specific cysteine disulfide bridge.
Alignment of the cytosolic CARPs revealed an evolutionary conserved R-H-Q motif
in place of the characteristic zinc-binding H-H-H necessary for the catalytic
function of alpha-CAs.
PMID- 27513960
TI - Linagliptin Ameliorates Methylglyoxal-Induced Peritoneal Fibrosis in Mice.
AB - Recent studies have reported increases of methylglyoxal (MGO) in peritoneal
dialysis patients, and that MGO-mediated inflammation plays an important role in
the development of peritoneal fibrosis through production of transforming growth
factor-beta1 (TGF-beta1). Linagliptin, a dipeptidyl peptidase-4 inhibitor, exerts
anti-inflammatory effects independent of blood glucose levels. In this study, we
examined whether linagliptin suppresses MGO-induced peritoneal fibrosis in mice.
Male C57/BL6 mice were divided into three groups: control, MGO injection plus
saline, and MGO injection plus linagliptin (n = 6 per group). Peritoneal fibrosis
was induced by daily intraperitoneal injection of saline containing 40 mmol/L MGO
for 21 days. Saline was administered intraperitoneally to the control group.
Linagliptin (10 mg/kg) or saline were administrated by once-daily oral gavage
from 3 weeks before starting MGO injections. Immunohistochemical staining
revealed that linagliptin suppressed expression of alpha-smooth muscle actin and
fibroblast-specific protein-1, deposition of type I and III collagen, and
macrophage (F4/80) infiltration. Peritoneal equilibration testing showed improved
peritoneal functions in mice treated with linagliptin. Peritoneal injection of
MGO increased plasma levels of glucagon-like peptide-1 (GLP-1) in mice, and a
further increase was observed in linagliptin-treated mice. Although MGO increased
plasma glucose levels, linagliptin did not decrease plasma glucose levels.
Moreover, linagliptin reduced the TGF-beta1 concentration in the peritoneal fluid
of MGO-treated mice. GLP-1 receptor (GLP-1R) was expressed in
monocytes/macrophages and linagliptin suppressed GLP-1R expression in MGO
injected mice. These results suggest that oral administration of linagliptin
ameliorates MGO-induced peritoneal fibrosis.
PMID- 27513961
TI - Metabolic Response to Heat Stress in Late-Pregnant and Early Lactation Dairy
Cows: Implications to Liver-Muscle Crosstalk.
AB - Climate changes lead to rising temperatures during summer periods and dramatic
economic losses in dairy production. Modern high-yielding dairy cows experience
severe metabolic stress during the transition period between late gestation and
early lactation to meet the high energy and nutrient requirements of the fetus or
the mammary gland, and additional thermal stress during this time has adverse
implications on metabolism and welfare. The mechanisms enabling metabolic
adaptation to heat apart from the decline in feed intake and milk yield are not
fully elucidated yet. To distinguish between feed intake and heat stress related
effects, German Holstein dairy cows were first kept at thermoneutral conditions
at 15 degrees C followed by exposure to heat-stressed (HS) at 28 degrees C or
pair-feeding (PF) at 15 degrees C for 6 days; in late-pregnancy and again in
early lactation. Liver and muscle biopsies and plasma samples were taken to
assess major metabolic pathway regulation using real-time PCR and Western Blot.
The results indicate that during heat stress, late pregnant cows activate Cahill
but reduce Cori cycling, prevent increase in skeletal muscle fatty acid
oxidation, and utilize increased amounts of pyruvate for gluconeogenesis, without
altering ureagenesis despite reduced plane of nutrition. These homeorhetic
adaptations are employed to reduce endogenous heat production while diverting
amino acids to the growing fetus. Metabolic adaptation to heat stress in early
lactation involves increased long-chain fatty acid degradation in muscle
peroxisomes, allowance for muscle glucose utilization but diminished hepatic use
of amino acid-derived pyruvate for gluconeogenesis and reduced peroxisomal fatty
acid oxidation and ATP production in liver of HS compared to PF cows in early
lactation. Consequently, metabolic adaptation to heat stress and reduced feed
intake differ between late pregnancy and early lactation of dairy cows to
maintain energy supply for fetus development or milk production simultaneously
reducing endogenous heat production.
PMID- 27513962
TI - Acid-sensing ion channels and transient-receptor potential ion channels in
zebrafish taste buds.
AB - Sensory information from the environment is required for life and survival, and
it is detected by specialized cells which together make up the sensory system.
The fish sensory system includes specialized organs that are able to detect
mechanical and chemical stimuli. In particular, taste buds are small organs
located on the tongue in terrestrial vertebrates that function in the perception
of taste. In fish, taste buds occur on the lips, the flanks, and the caudal
(tail) fins of some species and on the barbels of others. In fish taste receptor
cells, different classes of ion channels have been detected which, like in
mammals, presumably participate in the detection and/or transduction of chemical
gustatory signals. However, since some of these ion channels are involved in the
detection of additional sensory modalities, it can be hypothesized that taste
cells sense stimuli other than those specific for taste. This mini-review
summarizes current knowledge on the presence of transient-receptor potential
(TRP) and acid-sensing (ASIC) ion channels in the taste buds of teleosts,
especially adult zebrafish. Up to now ASIC4, TRPC2, TRPA1, TRPV1 and TRPV4 ion
channels have been found in the sensory cells, while ASIC2 was detected in the
nerves supplying the taste buds.
PMID- 27513963
TI - Progressive Decline in Height Standard Deviation Scores in the First 5 Years of
Life Distinguished Idiopathic Growth Hormone Deficiency from Familial Short
Stature and Constitutional Delay of Growth.
AB - BACKGROUND: Familial short stature (FSS) and constitutional delay of growth (CDG)
are the most frequent norm variants in children presenting with short stature.
Knowing the growth patterns of these entities in the first years of life might be
helpful to distinguish them from growth hormone deficiency (GHD) or other chronic
diseases. METHODS: We studied the height in the first 5 years of life in 26
children with FSS, in 38 children with CDG and in 14 children with idiopathic
GHD. RESULTS: Height standard deviation scores (SDS) did not change between birth
and 6 months of life, while height SDS decreased significantly afterwards in GHD,
FSS, and CDG. The loss of height SDS was higher in the first 2 years of life than
between 2 and 5 years of life in children with CDG (-0.92 vs. -0.11; p = 0.003)
or FSS (-0.79 vs. -0.01; p = 0.002). In idiopathic GHD, the loss of height SDS
did not differ between the first 2 years of life and the next 3 years (-0.78 vs.
0.77; p = 0.821). CONCLUSION: Children with FSS and CDG showed a decline in
height SDS mainly in the first 2 years of life, whereas the height SDS of
children with idiopathic GHD decreased almost continuously over the first 5 years
of life.
PMID- 27513964
TI - Farm-scale evaluation of the impact of Cry1Ab Bt maize on canopy nontarget
arthropods: a 3-year study.
AB - The cultivation of Cry1Ab-expressing genetically modified MON810 (Bt maize) has
led to public concern in Europe, regarding its impact on nontarget arthropods
(NTAs). We have assessed the potential effects of DKC 6451 YG (MON810) maize on
canopy NTAs in a farm-scale study performed in Central Spain during 3 years. The
study focused on hemipteran herbivores (leafhoppers and planthoppers) and
hymenopteran parasitic wasps (mymarids) collected by yellow sticky traps, which
accounted for 72% of the total number of insects studied. The dynamics and
abundance of these groups varied among years, but no significant differences were
found between Bt and non-Bt maize, indicating that Bt maize had no negative
effect on these taxa. Nonetheless, the Cry1Ab toxin was detected in 2 different
arthropods collected from Bt maize foliage, the cicadellids Zyginidia scutellaris
and Empoasca spp. A retrospective power analysis on the arthropod abundance data
for our field trials has determined that Z. scutellaris and the family Mymaridae
have high capacity to detect differences between the Bt maize and its isogenic
counterpart. The use of these canopy NTAs as surrogates for assessing
environmental impacts of Bt maize is discussed.
PMID- 27513965
TI - Difficult 32-Fr Double-Lumen Tube Intubation in a Small Japanese Woman With
Narrow Transverse Width of the Cricoid Cartilage.
AB - We encountered difficulty in inserting a 32-Fr left double-lumen tube (DLT) in a
small 75-year-old Japanese woman (height, 144 cm). The 32-Fr DLT with 10.1 * 11.2
mm tracheal diameter could not pass through the cricoid cartilage with a 9.2-mm
transverse inner width. The transverse inner width of the cricoid cartilage, in
addition to the tracheal and bronchial diameter, can be measured using computed
tomography or ultrasonography in small women. Thus, a 28-Fr DLT or single-lumen
tube and a blocker can be selected instead of a 32-Fr DLT when the width of the
cricoid cartilage is <10 mm.
PMID- 27513966
TI - Anesthetic Considerations for Neuraxial Anesthesia in Pregnant Patients With
Pityriasis Rosea With Skin Lesions Covering the Lumbar Spine.
AB - Pityriasis rosea (PR) is an acute exanthematous skin disease that is likely due
to reactivation of human herpesviruses (HHVs) 6b and 7. In contrast to herpes
simplex and zoster (alphaherpesviruses), HHV-6b and -7 (betaherpesviruses) are
not found predominantly in skin lesions. This difference in virion location may
decrease the possibility of causing central nervous system infection through skin
contamination, but the risk for hematogenous spread likely remains the same. This
article uses the first-known epidural placement through active PR to illustrate
risk-benefit considerations when deciding between neuraxial and general
anesthesia for obstetric patients with PR.
PMID- 27513967
TI - Periarticular Morphine-Induced Sphincter of Oddi Spasm Causing Severe Pain and
Bradycardia in an Awake Patient Under Spinal Anesthesia: An Important Diagnostic
Consideration.
AB - Sphincter of Oddi spasm from opioids has been documented, presenting as severe
epigastric pain and potentially overlooked in a differential diagnosis. We
present a case of sphincter of Oddi spasm from periarticular morphine in a
patient under spinal anesthesia, causing severe distress and treated effectively
with glucagon. It is important for anesthesiologists using opioids to consider it
as a cause of perioperative pain and be familiar with treatment as it may be
refractory by conventional use of opioids for pain relief. It is also important
to consider the systemic effects of periarticular absorption, as evident by our
case.
PMID- 27513968
TI - Anesthetic Management for Cesarean Delivery in a Patient With Pulmonary Emboli,
Pulmonary Hypertension, and Right Ventricular Failure.
AB - The maternal mortality rate for parturients with severe pulmonary hypertension is
30% to 50%. General, epidural, and combined low-dose spinal-epidural anesthesia
have been used successfully for cesarean deliveries in patients with pulmonary
hypertension. We describe a cesarean delivery performed using an intrathecal
catheter in a 25-year-old morbidly obese (body mass index, 82 kg/m) woman
(gravida 3, para 2 at 32 weeks of gestation) who had severe pulmonary
hypertension, right ventricular failure, pulmonary emboli, and obstructive sleep
apnea. We discuss the anesthetic considerations for parturients with severe
pulmonary hypertension undergoing cesarean delivery including the selection of
anesthetic technique, vasopressors, and uterotonic agents.
PMID- 27513969
TI - Bilateral Continuous Suprascapular Nerve Blocks for Bilateral Shoulder
Hemiarthroplasty.
AB - We report a novel case of a patient undergoing a bilateral shoulder
hemiarthroplasty for chronic bilateral shoulder dislocations with proximal
humeral fractures. Bilateral selective suprascapular nerve catheters were placed
preoperatively with the intent to provide continuous local anesthetic-based
analgesia while sparing diaphragmatic function. Postoperative respiratory
mechanics were relatively spared while numerical rating scale pain scores were
suggestive of analgesic benefit.
PMID- 27513970
TI - Successful Anticoagulation Using Argatroban During Transcatheter Aortic Valve
Implantation in a Patient With Heparin-Induced Thrombocytopenia.
AB - We report the first case of transfemoral transcatheter aortic valve implantation
with a history of heparin-induced thrombocytopenia that was successfully managed
with perioperative argatroban.
PMID- 27513971
TI - Continuous Noninvasive Hemodynamic Monitoring in an Infant With Tetra-Amelia.
AB - Tetra-amelia syndrome is a congenital disorder associated with near or complete
absence of all 4 limbs. Noninvasive hemodynamic monitoring may be difficult or
impossible in such patients. We describe the use of a finger cuff blood pressure
system for continuous noninvasive blood pressure monitoring in an infant with
near-complete tetra-amelia undergoing laparoscopic gastrostomy tube placement.
This case suggests the potential use of such a blood pressure monitoring system
for other patients with comparable deformities.
PMID- 27513972
TI - Continuous Quadratus Lumborum Block for Postoperative Pain in Total Hip
Arthroplasty: A Case Report.
AB - A 69-year-old man with a history of chronic pain and opioid use presented for
total hip arthroplasty. In the interests of ensuring early mobilization and pain
control, we chose a continuous quadratus lumborum block technique, a novel
ultrasound-guided block that has not yet been described for total hip
arthroplasty, hypothesizing that it would be motor-sparing. While the perineural
catheter was infused, the patient required no IV opioids. He was able to ambulate
on the first postoperative day, reporting pain scores between 0 and 3/10. The
quadratus lumborum block is a promising technique that, in our patient, was motor
sparing and provided excellent pain control.
PMID- 27513973
TI - Fhit loss-associated initiation and progression of neoplasia in vitro.
AB - The FHIT gene, encompassing an active common fragile site, FRA3B, is frequently
silenced in preneoplasia and cancer, through gene rearrangement or methylation of
regulatory sequences. Silencing of Fhit protein expression causes thymidine
kinase 1 downregulation, resulting in dNTP imbalance, and spontaneous replication
stress that leads to chromosomal aberrations, allele copy number variations,
insertions/deletions, and single-base substitutions. Thus, Fhit, which is reduced
in expression in the majority of human cancers, is a genome "caretaker" whose
loss initiates genome instability in preneoplastic lesions. To follow the early
genetic alterations and functional changes induced by Fhit loss that may
recapitulate the neoplastic process in vitro, we established epithelial cell
lines from kidney tissues of Fhit-/- and +/+ mouse pups early after weaning, and
subjected cell cultures to nutritional and carcinogen stress, which +/+ cells did
not survive. Through transcriptome profiling and protein expression analysis, we
observed changes in the Trp53/p21 and survivin apoptotic pathways in -/- cells,
and in expression of proteins involved in epithelial-mesenchymal transition. Some
Fhit-deficient cell lines showed anchorage-independent colony formation and
increased invasive capacity in vitro. Furthermore, cells of stressed Fhit-/- cell
lines formed s.c. and metastatic tumors in nude mice. Collectively, we show that
Fhit loss and subsequent thymidine kinase 1 inactivation, combined with selective
pressures, leads to neoplasia-associated alterations in genes and gene expression
patterns in vitro and in vivo.
PMID- 27513974
TI - MAB_3551c encodes the primary triacylglycerol synthase involved in lipid
accumulation in Mycobacterium abscessus.
AB - Slow growing pathogenic mycobacteria utilize host-derived lipids and accumulate
large amounts of triacylglycerol (TAG) in the form of intracytoplasmic lipid
inclusions (ILI), serving as a source of carbon and energy during prolonged
infection. Mycobacterium abscessus is an emerging and rapidly growing species
capable to induce severe and chronic pulmonary infections. However, whether M.
abscessus, like Mycobacterium tuberculosis, possesses the machinery to acquire
and store host lipids, remains unaddressed. Herein, we aimed at deciphering the
contribution of the seven putative M. abscessus TAG synthases (Tgs) in TAG
synthesis/accumulation thanks to a combination of genetic and biochemical
techniques and a well-defined foamy macrophage (FM) model along with electron
microscopy. Targeted gene deletion and functional complementation studies
identified the MAB_3551c product, Tgs1, as the major Tgs involved in TAG
production. Tgs1 exhibits a preference for long acyl-CoA substrates and site
directed mutagenesis demonstrated that His144 and Gln145 are essential for
enzymatic activity. Importantly, in the lipid-rich intracellular context of FM,
M. abscessus formed large ILI in a Tgs1-dependent manner. This supports the
ability of M. abscessus to assimilate host lipids and the crucial role of Tgs1 in
intramycobacterial TAG production, which may represent important mechanisms for
long-term storage of a rich energy supply.
PMID- 27513975
TI - Correction: Recalculating the Net Use Gap: A Multi-Country Comparison of ITN Use
versus ITN Access.
AB - [This corrects the article DOI: 10.1371/journal.pone.0097496.].
PMID- 27513976
TI - QTLs Associated with Agronomic Traits in the Cutler * AC Barrie Spring Wheat
Mapping Population Using Single Nucleotide Polymorphic Markers.
AB - We recently reported three earliness per se quantitative trait loci (QTL)
associated with flowering and maturity in a recombinant inbred lines (RILs)
population derived from a cross between the spring wheat (Triticum aestivum L.)
cultivars 'Cutler' and 'AC Barrie' using 488 microsatellite and diversity arrays
technology (DArT) markers. Here, we present QTLs associated with flowering time,
maturity, plant height, and grain yield using high density single nucleotide
polymorphic (SNP) markers in the same population. A mapping population of 158
RILs and the two parents were evaluated at five environments for flowering,
maturity, plant height and grain yield under field conditions, at two greenhouse
environments for flowering, and genotyped with a subset of 1809 SNPs out of the
90K SNP array and 2 functional markers (Ppd-D1 and Rht-D1). Using composite
interval mapping on the combined phenotype data across all environments, we
identified a total of 19 QTLs associated with flowering time in greenhouse (5),
and field (6) conditions, maturity (5), grain yield (2) and plant height (1). We
mapped these QTLs on 8 chromosomes and they individually explained between 6.3
and 37.8% of the phenotypic variation. Four of the 19 QTLs were associated with
multiple traits, including a QTL on 2D associated with flowering, maturity and
grain yield; two QTLs on 4A and 7A associated with flowering and maturity, and
another QTL on 4D associated with maturity and plant height. However, only the
QTLs on both 2D and 4D had major effects, and they mapped adjacent to well-known
photoperiod response Ppd-D1 and height reducing Rht-D1 genes, respectively. The
QTL on 2D reduced flowering and maturity time up to 5 days with a yield penalty
of 436 kg ha-1, while the QTL on 4D reduced plant height by 13 cm, but increased
maturity by 2 days. The high density SNPs allowed us to map eight moderate
effect, two major effect, and nine minor effect QTLs that were not identified in
our previous study using microsatellite and DArT markers. Results from this study
provide additional information to wheat researchers developing early maturing and
short stature spring wheat cultivars.
PMID- 27513977
TI - Danio rerio embryos on Prozac - Effects on the detoxification mechanism and
embryo development.
AB - In the past decade the presence of psychopharmaceuticals, including fluoxetine
(FLU), in the aquatic environment has been associated with the increasing trend
in human consumption of these substances. Aquatic organisms are usually exposed
to chronic low doses and, therefore, risk assessments should evaluate the effects
of these compounds in non-target organisms. Teleost fish possess an array of
active defence mechanisms to cope with the deleterious effects of xenobiotics.
These include ABC transporters, phase I and II of cellular detoxification and
oxidative stress enzymes. Hence, the present study aimed at characterising the
effect of FLU on embryo development of the model teleost zebrafish (Danio rerio)
concomitantly with changes in the detoxification mechanisms during early
developmental phases. Embryos were exposed to different concentrations of FLU
(0.0015, 0.05, 0.1, 0.5 and 0.8MUM) for 80hours post fertilization. Development
was screened and the impact in the transcription of key genes, i.e., abcb4,
abcc1, abcc2, abcg2, cyp1a, cyp3a65, gst, sod, cat, ahr, pxr, pparalpha,
pparbeta, ppargamma, rxraa, rxrab, rxrbb, rxrga, rxrgb, raraa, rarab, rarga
evaluated. In addition, accumulation assays were performed to measure the
activity of ABC proteins and antioxidant enzymes (CAT and Cu/ZnSOD) after
exposure to FLU. Embryo development was disrupted at the lowest FLU concentration
tested (0.0015MUM), which is in the range of concentrations found in WWTP
effluents. Embryos exposed to higher concentrations of FLU decreased Cu/Zn SOD,
and increased CAT (0.0015 and 0.5MUM) enzymatic activity. Exposure to higher
concentrations of FLU decreased the expression of most genes belonging to the
detoxification system and upregulated cat at 0.0015MUM of FLU. Most of the tested
concentrations downregulated pparalpha, pparbeta, ppargamma, and raraa, rxraa,
rxrab, rxrbb rxrgb and ahr gene expression while pxr was significantly up
regulated at all tested concentrations. In conclusion, this study shows that FLU
can impact zebrafish embryo development, at concentrations found in effluents of
WWTPs, concomitantly with changes in antioxidant enzymes, and the transcription
of key genes involved in detoxification and development. These finding raises
additional concerns supporting the need to monitor the presence of this compound
in aquatic reservoirs.
PMID- 27513979
TI - Intracranial angiomatous meningiomas: A 15-year, multicenter study.
AB - BACKGROUND: Angiomatous meningiomas (AMs) represent a rare subtype of meningiomas
in which the vascular component prevail. They represent less than 1% of all
intracranial tumors and approximately 2.1% of all meningeal tumors (Hasselblatt
et al., 2004). The purpose of this study was to determine the clinical
characteristics, radiological features and prognosis of AMs based on a Tunisian
multicenter experience in the management of 58 successive cases of intracranial
AMs. To the best of our knowledge, this is the largest series reported to date.
METHODS: We retrospectively reviewed 58 patients of AM treated in the departments
of Neurosurgery of The Tunisian National Institute of Neurology, Sahloul
University Hospital and Fattouma Bourguiba University Hospital from January 2001
to December 2015. Clinical characteristics, radiographic features and treatment
modality, in the form of radical surgery, were noted. Statistical analysis was
done with regards to recurrence free survival (RFS) and overall survival (OS)
using Kaplan-Meier survival analysis. RESULTS: The median age of the patients on
admission was 53.0 years (8-78). Twenty-two patients were males and thirty-six
were females. The median duration of symptoms prior to presentation was six
months. Signs of increased intracranial pressure were the most common presenting
symptom followed by seizures, motor weakness and cranial nerves paresis. Cystic
changes were observed in 50% of cases, moderate to severe peritumoral edema in
81% of cases and multiple signal voids suggestive of blood vessels in 86.2% of
cases. Forty-two patients underwent Simpson I excision (72.4%) while fourteen had
Simpson II excision (24.1%). A Simpson III resection was realized in two patients
(3.5%). The surgical resection was hemorrhagic in 63.8% of cases and in 13.8% of
cases, several blood transfusions were necessary to maintain hemodynamic
stability. No adjunctive treatment was administered. Six out of the fifty-six
patients of the Simpson I/II groups recurred while one of the two patients with
Simpson III resection had tumor regrowth. Median duration of RFS was 103 months.
Second surgery was realized in all cases with no subsequent recurrence. The
extent of tumor resection and the location were found to correlate with the risk
of developing recurrences (P=0.001). CONCLUSIONS: AMs represent a rare subtype of
meningioma characterized by variable cystic components, large peritumoral edema
and multiple areas of vascular signal voids. The mainstay of the treatment is
gross total resection, ideally following a preoperative embolization. The fate of
the tumor remnant after incomplete tumor resection still needs to be evaluated
and we do not recommend the systematic use of post-operative adjuvant RT in all
cases. As local recurrence can develop many years after initial treatment, Long
term follow-up is mandatory.
PMID- 27513978
TI - Locus coeruleus volume and cell population changes during Alzheimer's disease
progression: A stereological study in human postmortem brains with potential
implication for early-stage biomarker discovery.
AB - INTRODUCTION: Alzheimer's disease (AD) progression follows a specific spreading
pattern, emphasizing the need to characterize those brain areas that degenerate
first. The brainstem's locus coeruleus (LC) is the first area to develop
neurofibrillary changes (neurofibrillary tangles [NFTs]). METHODS: The methods
include unbiased stereological analyses in human brainstems to estimate LC volume
and neuronal population in controls and individuals across all AD stages.
RESULTS: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%.
Neuronal loss started only midway through AD progression. Age-related changes
spare the LC. DISCUSSION: The long gap between NFT accumulation and neuronal loss
suggests that a second trigger may be necessary to induce neuronal death in AD.
Imaging studies should determine whether LC volumetry can replicate the stage
wise atrophy observed here and how these changes are specific to AD. LC volumetry
may develop into a screening biomarker for selecting high-yield candidates to
undergo expensive and less accessible positron emission tomography scans and to
monitor AD progression from presymptomatic stages.
PMID- 27513980
TI - Lower cervical levels: Increased risk of early dysphonia following anterior
cervical spine surgery.
AB - OBJECTIVES: The present study aimed to re-evaluate the incidence of early
dysphonia after anterior cervical spine surgery (ACSS) and to determine the
related risk factors. CLINICAL MATERIALS AND METHODS: Patients underwent ACSS
between January 2011 and December 2013 at two sites were identified
retrospectively from hospital's patient databases. A total of 233 cases were
included in this study. Dysphonia developed 1 month postoperatively was recorded.
Follow-up was conducted in all positive-response patients. Those reporting severe
or persistent voice symptoms were referred to otolaryngologists for further
assessments and (or) treatments. Pre and intraoperative factors were collected to
determine their relationships with dysphonia one month postoperatively. RESULTS:
45 patients developed dysphonia at one month, including 23 males and 22 females,
yielding to an incidence of 19.3%. 34 cases resolved themselves in 3 months,
leaving the remaining 11 patients considered to be severe or persistent cases.
However, 10 of them recovered spontaneously in the next 9 months, while the last
case received vocal cord medialization and returned to almost normal speech
function at 18 months. In univariate analysis, only approaching level involving
C6-C7 or (and) C7-T1 was significantly associated with postoperative dysphonia
(P<0.001). This association was not weakened in multiple logistic regression
analysis (OR 2.348, 95% CI 1.467-3.659, P<0.001). CONCLUSION: The incidence of
early dysphonia following ACSS was relatively high and approaching at lower
cervical levels was an independent predictive factor.
PMID- 27513981
TI - The developmental transcriptome atlas of the biofuel crop Camelina sativa.
AB - Camelina sativa is currently being embraced as a viable industrial bio-platform
crop due to a number of desirable agronomic attributes and the unique fatty acid
profile of the seed oil that has applications for food, feed and biofuel. The
recent completion of the reference genome sequence of C. sativa identified a
young hexaploid genome. To complement this work, we have generated a genome-wide
developmental transcriptome map by RNA sequencing of 12 different tissues
covering major developmental stages during the life cycle of C. sativa. We have
generated a digital atlas of this comprehensive transcriptome resource that
enables interactive visualization of expression data through a searchable
database of electronic fluorescent pictographs (eFP browser). An analysis of this
dataset supported expression of 88% of the annotated genes in C. sativa and
provided a global overview of the complex architecture of temporal and spatial
gene expression patterns active during development. Conventional differential
gene expression analysis combined with weighted gene expression network analysis
uncovered similarities as well as differences in gene expression patterns between
different tissues and identified tissue-specific genes and network modules. A
high-quality census of transcription factors, analysis of alternative splicing
and tissue-specific genome dominance provided insight into the transcriptional
dynamics and sub-genome interplay among the well-preserved triplicated repertoire
of homeologous loci. The comprehensive transcriptome atlas in combination with
the reference genome sequence provides a powerful resource for genomics research
which can be leveraged to identify functional associations between genes and
understand the regulatory networks underlying developmental processes.
PMID- 27513982
TI - Skin punch biopsy sectioning: before or after tissue processing?
AB - BACKGROUND: We intended to study whether there is a meaningful difference in
microscopic examination between dividing a biopsy section into two equal parts
before tissue processing (first method) or after (second method). METHODS: A
total of 400 cases were included in the study. Punch biopsies (PB) were cut into
two pieces using the first method in 200 cases and just before paraffin embedding
in another 200 cases using the second method. We microscopically evaluated the
epidermal mesh view, the presence of a cross-cut hair follicle and bow shape
because of epidermal angling, the presence of two pieces on the slide and if
there was a difference of >2 mm between the parts, and the number of new sections
and new slides. RESULTS: Cross-cut hair follicle (p = 0.018), epidermal mesh view
(p = 0.036), difference of >2 mm between the parts (p = 0.008), the number of new
sections (p < 0.001) and new slides (p < 0.001) were considerably higher when the
first method was used compared with the second method. The presence of two pieces
was less (p < 0.001) when using the first method. CONCLUSIONS: We noted a
meaningful difference in the quality of microscopic evaluation between the first
and second methods. Better sections were obtained with the second method. In
addition, the decrease in the number of new slides will reduce workload, archival
work and cost.
PMID- 27513983
TI - Peak Systolic Velocity Measurements with Transcranial Doppler Ultrasound Is a
Predictor of Incident Stroke among the General Population in China.
AB - BACKGROUND AND OBJECTIVE: It is necessary to develop an effective and low-cost
screening tool for identifying Chinese people at high risk of stroke.
Transcranial Doppler ultrasound (TCD) is a powerful predictor of stroke in the
pediatric sickle cell disease population, as demonstrated in the STOP trial. Our
study was conducted to determine the prediction value of peak systolic velocities
as measured by TCD on subsequent stroke risk in a prospective cohort of the
general population from Beijing, China. METHODS: In 2002, a prospective cohort
study was conducted among 1392 residents from 11 villages of the Shijingshan
district of Beijing, China. The cohort was scheduled for follow up with regard to
incident stroke in 2005, 2007, and 2012 by a study team comprised of
epidemiologists, nurses, and physicians. Univariate and multivariate Cox
proportional hazard regression models were used to determine the factors
associated with incident stroke. RESULTS: Participants identified by TCD criteria
as having intracranial stenosis had a 3.6-fold greater risk of incident stroke
(hazard ratio (HR) 3.57, 95% confidence interval (CI) 1.86-6.83, P<0.01) than
those without TCD evidence of intracranial stenosis. The association remained
significant in multivariate analysis (HR 2.53, 95% CI 1.31-4.87) after adjusting
for other risk factors or confounders. Older age, cigarette smoking,
hypertension, and diabetes mellitus remained statistically significant as risk
factors after controlling for other factors. CONCLUSIONS: The study confirmed the
screening value of TCD among the general population in urban China. Increasing
the availability of TCD screening may help identify subjects as higher risk for
stroke.
PMID- 27513984
TI - What can psychoanalysis contribute to the current refugee crisis?: Preliminary
reports from STEP-BY-STEP: A psychoanalytic pilot project for supporting refugees
in a "first reception camp" and crisis interventions with traumatized refugees.
PMID- 27513985
TI - Recent Chikungunya Virus Infection in 2 Travelers Returning from Mogadishu,
Somalia, to Italy, 2016.
PMID- 27513986
TI - Can We Predict Individual Combined Benefit and Harm of Therapy? Warfarin Therapy
for Atrial Fibrillation as a Test Case.
AB - OBJECTIVES: To construct and validate a prediction model for individual combined
benefit and harm outcomes (stroke with no major bleeding, major bleeding with no
stroke, neither event, or both) in patients with atrial fibrillation (AF) with
and without warfarin therapy. METHODS: Using the Kaiser Permanente Colorado
databases, we included patients newly diagnosed with AF between January 1, 2005
and December 31, 2012 for model construction and validation. The primary outcome
was a prediction model of composite of stroke or major bleeding using polytomous
logistic regression (PLR) modelling. The secondary outcome was a prediction model
of all-cause mortality using the Cox regression modelling. RESULTS: We included
9074 patients with 4537 and 4537 warfarin users and non-users, respectively. In
the derivation cohort (n = 4632), there were 136 strokes (2.94%), 280 major
bleedings (6.04%) and 1194 deaths (25.78%) occurred. In the prediction models,
warfarin use was not significantly associated with risk of stroke, but increased
the risk of major bleeding and decreased the risk of death. Both the PLR and Cox
models were robust, internally and externally validated, and with acceptable
model performances. CONCLUSIONS: In this study, we introduce a new methodology
for predicting individual combined benefit and harm outcomes associated with
warfarin therapy for patients with AF. Should this approach be validated in other
patient populations, it has potential advantages over existing risk
stratification approaches as a patient-physician aid for shared decision-making.
PMID- 27513987
TI - Giant Interfrontal Encephalocele in an Infant: A Rare Entity.
AB - Interfrontal encephalocele is one of the rare varieties of anterior
encephalocele, and a giant interfrontal encephalocele is extremely rare. The
authors could find only one case report of giant interfrontal encephalocele in
the literature. Anterior encephaloceles are more prevalent in South-East Asia and
some northern parts of India. Giant encephalocele poses a great challenge to
neurosurgeons and neuroanesthetists during surgery, as these infants usually have
a low birth weight and a large sac, thus making the infant prone to hypothermia
and blood loss among other risks. We encountered a patient with a giant
interfrontal encephalocele aged 1 month. The rarity of this case prompted us to
this report.
PMID- 27513988
TI - Enhanced Electrochemical Kinetics on Conductive Polar Mediators for Lithium
Sulfur Batteries.
AB - Lithium-sulfur (Li-S) batteries have been recognized as promising substitutes for
current energy-storage technologies owing to their exceptional advantage in
energy density. The main challenge in developing highly efficient and long-life
Li-S batteries is simultaneously suppressing the shuttle effect and improving the
redox kinetics. Polar host materials have desirable chemisorptive properties to
localize the mobile polysulfide intermediates; however, the role of their
electrical conductivity in the redox kinetics of subsequent electrochemical
reactions is not fully understood. Conductive polar titanium carbides (TiC) are
shown to increase the intrinsic activity towards liquid-liquid polysulfide
interconversion and liquid-solid precipitation of lithium sulfides more than non
polar carbon and semiconducting titanium dioxides. The enhanced electrochemical
kinetics on a polar conductor guided the design of novel hybrid host materials of
TiC nanoparticles grown within a porous graphene framework (TiC@G). With a high
sulfur loading of 3.5 mg cm-2 , the TiC@G/sulfur composite cathode exhibited a
substantially enhanced electrochemical performance.
PMID- 27513989
TI - Population pharmacokinetics of a new long-acting recombinant coagulation factor
IX albumin fusion protein for patients with severe hemophilia B.
AB - Essentials The new recombinant factor IX (FIX) albumin fusion protein (rIX-FP)
has a prolonged half-life. A population pharmacokinetic (PK) model was based on
FIX activity levels of hemophilia B patients. The model was used to simulate
different dosing scenarios of rIX-FP to help guide dosing. The population PK
model supported prolonged dosing of rIX-FP with intervals of up to 2 weeks. Click
to hear Prof.Makris's presentation on new treatments in hemophilia SUMMARY:
Background The recombinant fusion protein linking recombinant coagulation factor
IX with recombinant albumin (rIX-FP; Idelvion(r) ) exhibits a longer half-life
than plasma-derived factor IX (FIX) and the commercially available recombinant
FIX products. Objectives (i) Characterize the population pharmacokinetics (PK) of
rIX-FP in hemophilia B patients, (ii) identify covariates that are potential
determinants of rIX-FP PK variability and (iii) simulate different dosing
scenarios of rIX-FP following single and steady-state dosing. Patients/Methods A
population PK model was developed based on FIX activity levels of 104 patients
who had received treatment with rIX-FP. Patients were aged 1-65 years with FIX
activity <= 2 IU dL-1 . PK sampling was performed for up to 14 days (336 h).
Results Simulation of a single intravenous infusion of rIX-FP (25-75 IU kg-1 )
predicted that the median trough exogenous FIX activity levels would remain > 5
IU dL-1 for up to 16 days in adolescents/adults aged >= 12 years, up to 12 days
in children aged 6 to < 12 years, and up to 9.5 days in children aged < 6 years.
For steady-state dosing, the median trough exogenous FIX activity levels were
maintained at > 5 IU dL-1 for the duration of the dosing interval for the 25, 35
and 40 IU kg-1 weekly regimens and for 75 IU kg-1 every 14 days in
adolescents/adults, and for the 35 and 40 IU kg-1 weekly regimens in children.
Conclusion The population PK model developed here correlates well with observed
clinical data and supports prolonged dosing of rIX-FP with intervals of up to 2
weeks.
PMID- 27513990
TI - Genetic Determinants for Pyomelanin Production and Its Protective Effect against
Oxidative Stress in Ralstonia solanacearum.
AB - Ralstonia solanacearum is a soil-borne plant pathogen that infects more than 200
plant species. Its broad host range and long-term survival under different
environmental stress conditions suggest that it uses a variety of mechanisms to
protect itself against various types of biotic and abiotic stress. R.
solanacearum produces a melanin-like brown pigment in the stationary phase when
grown in minimal medium containing tyrosine. To gain deeper insight into the
genetic determinants involved in melanin production, transposon-inserted mutants
of R. solanacearum strain SL341 were screened for strains with defective melanin
producing capability. In addition to one mutant already known to be involved in
pyomelanin production (viz., strain SL341D, with disruption of the
hydroxphenylpyruvate dioxygenase gene), we identified three other mutants with
disruption in the regulatory genes rpoS, hrpG, and oxyR, respectively. Wild-type
SL341 produced pyomelanin in minimal medium containing tyrosine whereas the
mutant strains did not. Likewise, homogentisate, a major precursor of pyomelanin,
was detected in the culture filtrate of the wild-type strain but not in those of
the mutant strains. A gene encoding hydroxyphenylpyruvate dioxygenase exhibited a
significant high expression in wild type SL341 compared to other mutant strains,
suggesting that pyomelanin production is regulated by three different regulatory
proteins. However, analysis of the gene encoding homogentisate dioxygenase
revealed no significant difference in its relative expression over time in the
wild-type SL341 and mutant strains, except for SL341D, at 72 h incubation. The
pigmented SL341 strain also exhibited a high tolerance to hydrogen peroxide
stress compared with the non-pigmented SL341D strain. Our study suggests that
pyomelanin production is controlled by several regulatory factors in R.
solanacearum to confer protection under oxidative stress.
PMID- 27513992
TI - Post-flowering night respiration and altered sink activity account for high night
temperature-induced grain yield and quality loss in rice (Oryza sativa L.).
AB - High night temperature (HNT) is a major constraint to sustaining global rice
production under future climate. Physiological and biochemical mechanisms were
elucidated for HNT-induced grain yield and quality loss in rice. Contrasting rice
cultivars (N22, tolerant; Gharib, susceptible; IR64, high yielding with superior
grain quality) were tested under control (23 degrees C) and HNT (29 degrees C)
using unique field-based tents from panicle initiation till physiological
maturity. HNT affected 1000 grain weight, grain yield, grain chalk and amylose
content in Gharib and IR64. HNT increased night respiration (Rn) accounted for
higher carbon losses during post-flowering phase. Gharib and IR64 recorded 16 and
9% yield reduction with a 63 and 35% increase in average post-flowering Rn under
HNT, respectively. HNT altered sugar accumulation in the rachis and spikelets
across the cultivars with Gharib and IR64 recording higher sugar accumulation in
the rachis. HNT reduced panicle starch content in Gharib (22%) and IR64 (11%) at
physiological maturity, but not in the tolerant N22. At the enzymatic level, HNT
reduced sink strength with lower cell wall invertase and sucrose synthase
activity in Gharib and IR64, which affected starch accumulation in the developing
grain, thereby reducing grain weight and quality. Interestingly, N22 recorded
lower Rn-mediated carbon losses and minimum impact on sink strength under HNT.
Mechanistic responses identified will facilitate crop models to precisely
estimate HNT-induced damage under future warming scenarios.
PMID- 27513991
TI - Calpain inhibition reduces structural and functional impairment of retinal
ganglion cells in experimental optic neuritis.
AB - Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with
multiple sclerosis. ON pathology is characterized by attack of autoreactive T
cells against optic nerve antigens, resulting in demyelination, death of retinal
ganglion cells, and cumulative visual impairment. A model of experimental
autoimmune encephalomyelitis (EAE) was utilized to study the onset and
progression of ON and the neuroprotective efficacy of oral treatment with the
calpain inhibitor SNJ 1945. EAE was actively induced in B10.PL mice with myelin
basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ
1945 from Day 9 until sacrificing (Day 26). Visual function was determined by
electroretinogram recordings and daily measurement of optokinetic responses (OKR)
to a changing pattern stimulus. Optic nerve and retinal histopathology was
investigated by immunohistochemical and luxol fast blue staining. EAE mice
manifested losses in OKR thresholds, a measurement of visual acuity, which began
early in the disease course. There was a significant bias toward unilateral OKR
impairment among EAE-ON eyes. Treatment with SNJ 1945, initiated after the onset
of OKR threshold decline, improved visual acuity, pattern electroretinogram
amplitudes, and paralysis, with attenuation of retinal ganglion cell death.
Furthermore, calpain inhibition spared oligodendrocytes, prevented degradation of
axonal neurofilament protein, and attenuated reactive astrocytosis. The trend of
early, unilateral visual impairment in EAE-ON parallels the clinical presentation
of ON exacerbations associated with multiple sclerosis. Calpain inhibition may
represent an ideal candidate therapy for the preservation of vision in clinical
ON. As in multiple sclerosis (MS) patients, optic neuritis (ON) and early,
primarily monocular loss in spatial acuity is observed in a rodent model (EAE,
experimental autoimmune encephalomyelitis). Daily oral treatment with the calpain
inhibitor SNJ 1945 preserves visual acuity and preserves retinal ganglion cells
(Brn3a, brain-specific homeobox/POU domain protein 3A) and their axons (MOSP,
myelin oligodendrocyte-specific protein). Calpain inhibition may represent a
candidate therapy for the preservation of vision in ON.
PMID- 27513993
TI - 1 H and 13 C NMR spectral assignments of a new cyclic peptide from Glycosmis
lucida Wall. Ex Huang.
PMID- 27513994
TI - Identification of a novel mutation in PLA2G6 gene in a Chinese pedigree with
familial cortical myoclonic tremor with epilepsy.
AB - PURPOSE: Familial cortical myoclonic tremor with epilepsy (FCMTE) is an epileptic
syndrome with autosomal dominant inheritance, of which four genetic subtypes
(FCMTE1-4) have been reported. In the present study, we described the clinical
and neurophysiologic features of a newly diagnosed Chinese FCMTE family, and
investigated the genetic cause for this disease. METHODS: Clinical information
was obtained from affected and normal individuals of an FCMTE family comprising
41 members. Electroencephalographies were analyzed in five of six affected
members (including the proband). Brain magnetic resonance imaging, somatosensory
evoked potential with C-reflex analysis and magnetoencephalography was performed
in the proband. Genomic DNA of three affected and two unaffected individuals was
analyzed to detect the genetic mutations by using whole-exome sequencing.
RESULTS: The inheritance pattern of the pedigree was autosomal dominant. A novel
missense mutation c.475C>T (p.Ala159Thr) of PLA2G6 were identified in this
family. The mutated locus is highly conserved among other species. The mutation
is predicted to have a functional impact, and completely co-segregated with the
phenotype. CONCLUSION: This study identifies a novel PLA2G6 mutation that is the
possible genetic cause of FCMTE in this family. This mutation and associated
clinical features expand the spectrum and phenotypes of PLA2G6-related disorders
including neurodegenerative diseases.
PMID- 27513995
TI - Cervical and Breast Cancer Screening Among Mexican Migrant Women, 2013.
AB - INTRODUCTION: Information on cervical and breast cancer screening among Latinas
in the United States is limited. Even less information is available on screening
practices of migrant women who engage in circular migration. We examined rates of
cervical and breast cancer screening and the extent to which sociodemographics
and other characteristics explain screening practices of Mexican migrant women
who return to Mexico from the United States. METHODS: We used data from a cross
sectional probability survey of Mexico-born migrant women who returned, through
Tijuana, to Mexico from the United States in 2013. The sample consisted of women
who returned involuntarily (via deportation) or voluntarily; 177 reported
authorized documentation status, and 36 reported unauthorized documentation
status in the previous 12 months. Descriptive statistics were calculated and
logistic regressions were estimated. RESULTS: Of 36 undocumented migrant women, 8
(22.2%) had a Papanicolaou test and 11 (30.6%) had a mammogram in the previous
year; of 177 documented migrants, 83 (46.9%) had a Papanicolaou test and 68
(38.4%) had a mammogram. Undocumented migrants were less likely than documented
migrants to receive a Papanicolaou test (odds ratio [OR] = 0.29; 95% confidence
interval [CI], 0.12-0.67); the likelihood was similar after adjustment for
sociodemographic, migration, and acculturation factors (adjusted OR = 0.33; 95%
CI, 0.12-0.90). Having health insurance (adjusted OR = 4.17; 95% CI, 1.80-9.65)
and a regular source of health care (adjusted OR = 2.83; 95% CI, 1.05-7.65) were
significant predictors of receiving a mammogram but not a Papanicolaou test.
CONCLUSION: Public health programs are needed to improve access to cervical and
breast cancer screenings for Latina migrant women in general and undocumented
circular migrants in particular.
PMID- 27513996
TI - Developing a Tool to Assess the Capacity of Out-of-School Time Program Providers
to Implement Policy, Systems, and Environmental Change.
AB - BACKGROUND: Little is known about public health practitioners' capacity to change
policies, systems, or environments (PSEs), in part due to the absence of
measures. To address this need, we partnered with the Alliance for a Healthier
Generation (Alliance) to develop and test a theory-derived measure of the
capacity of out-of-school time program providers to improve students' level of
nutrition and physical activity through changes in PSEs. COMMUNITY CONTEXT: The
measure was developed and tested through an engaged partnership with staff
working on the Alliance's Healthy Out-of-School Time (HOST) Initiative. In total,
approximately 2,000 sites nationwide are engaged in the HOST Initiative, which
serves predominantly high-need children and youths. METHODS: We partnered with
the Alliance to conduct formative work that would help develop a survey that
assessed attitudes/beliefs, social norms, external resources/supports, and self
efficacy. The survey was administered to providers of out-of-school time programs
who were implementing the Alliance's HOST Initiative. OUTCOME: Survey respondents
were 185 out-of-school time program providers (53% response rate). Exploratory
factor analysis yielded a 4-factor model that explained 44.7% of the variance.
Factors pertained to perceptions of social norms (6 items) and self-efficacy to
build support and engage a team (4 items) and create (5 items) and implement (3
items) an action plan. INTERPRETATION: We report initial development and factor
analysis of a tool that the Alliance can use to assess the capacity of after
school time program providers, which is critical to targeting capacity-building
interventions and assessing their effectiveness. Study findings also will inform
the development of measures to assess individual capacity to plan and implement
other PSE interventions.
PMID- 27513997
TI - Comparison of 2 Disability Measures, Behavioral Risk Factor Surveillance System,
2013.
AB - INTRODUCTION: Beginning in 2013, in addition to the 2-item disability question
set asked since 2001, Behavioral Risk Factor Surveillance System (BRFSS) began
using 5 of the 6 items from the US Department of Health and Human Services
recommended disability question set. We assess and compare disability prevalence
using the 2-question and 5-question sets and describe characteristics of
respondents who identified as having a disability using each question set.
METHODS: We used data from the 2013 BRFSS to estimate the prevalence of
disability for each question set and the 5 specific types of disability. Among
respondents identified by each disability question set, we calculated the
prevalence of selected demographic characteristics, health conditions, health
behaviors, and health status. RESULTS: With the 2-question set, 21.6% of adults
had a disability and with the 5-question set, 22.7% of adults had disability. A
total of 51.2% of adults who identified as having a disability with either the 2
question or 5-question set reported having disabilities with both sets. Adults
with different disability types differed by demographic and health
characteristics. CONCLUSION: The inclusion of the 5 new disability questions in
BRFSS provides a level of detail that can help develop targeted interventions and
programs and can guide the adaptation of existing health promotion programs to be
more inclusive of adults who experience specific types of disabilities.
PMID- 27513998
TI - Using Photovoice and Asset Mapping to Inform a Community-Based Diabetes
Intervention, Boston, Massachusetts, 2015.
AB - INTRODUCTION: Diabetes self-management takes place within a complex social and
environmental context. This study's objective was to examine the perceived and
actual presence of community assets that may aid in diabetes control. METHODS: We
conducted one 6-hour photovoice session with 11 adults with poorly controlled
diabetes in Boston, Massachusetts. Participants were recruited from census
tracts with high numbers of people with poorly controlled diabetes (diabetes "hot
spots"). We coded the discussions and identified relevant themes. We further
explored themes related to the built environment through community asset mapping.
Through walking surveys, we evaluated 5 diabetes hot spots related to physical
activity resources, walking environment, and availability of food choices in
restaurants and food stores. RESULTS: Community themes from the photovoice
session were access to healthy food, restaurants, and prepared foods; food
assistance programs; exercise facilities; and church. Asset mapping identified
114 community assets including 22 food stores, 22 restaurants, and 5 exercise
facilities. Each diabetes hot spot contained at least 1 food store with 5 to 9
varieties of fruits and vegetables. Only 1 of the exercise facilities had
signage regarding hours or services. Memberships ranged from free to $9.95 per
month. Overall, these findings were inconsistent with participants' reports in
the photovoice group. CONCLUSION: We identified a mismatch between perceptions of
community assets and built environment and the objective reality of that
environment. Incorporating photovoice and community asset mapping into a
community-based diabetes intervention may bring awareness to underused
neighborhood resources that can help people control their diabetes.
PMID- 27514000
TI - Supporting fathers is essential in the child health field.
PMID- 27514001
TI - Medical champions can make a difference in initiating culture change.
PMID- 27514002
TI - Cooled infants with encephalopathy: are heavier infants with weaker heart at a
cutaneous disadvantage?
PMID- 27514003
TI - Sleep problems in children with dyslexia: understanding the role of sleep in
neurocognitive development through the lens of developmental disorders.
PMID- 27514004
TI - Role of connectome-based analysis techniques in functional neuroimaging
investigations of neurodevelopmental disorders.
PMID- 27514005
TI - What else are you hoping for? Fostering hope in paediatric serious illness.
PMID- 27514006
TI - Nebulised hypertonic saline for acute bronchiolitis or 'there and back again' to
use Tolkien's subtitle for The Hobbit.
PMID- 27514007
TI - Validating a robust double-quantum-filtered (1) H MRS lactate measurement method
in high-grade brain tumours.
AB - (1) H MRS measurements of lactate are often confounded by overlapping lipid
signals. Double-quantum (DQ) filtering eliminates lipid signals and permits
single-shot measurements, which avoid subtraction artefacts in moving tissues.
This study evaluated a single-voxel-localized DQ filtering method qualitatively
and quantitatively for measuring lactate concentrations in the presence of lipid,
using high-grade brain tumours in which the results could be compared with
standard acquisition as a reference. Paired standard acquisition and DQ-filtered
(1) H MR spectra were acquired at 3T from patients receiving treatment for
glioblastoma, using fLASER (localization by adiabatic selective refocusing using
frequency offset corrected inversion pulses) single-voxel localization. Data were
acquired from 2 * 2 * 2 cm(3) voxels, with a repetition time of 1 s and 128
averages (standard acquisition) or 256 averages (DQ-filtered acquisition),
requiring 2.15 and 4.3 min respectively. Of 37 evaluated data pairs, 20 cases
(54%) had measureable lactate (fitted Cramer-Rao lower bounds <= 20%) in either
the DQ-filtered or the standard acquisition spectra. The measured DQ-filtered
lactate signal was consistently downfield of lipid (1.33 +/- 0.03 ppm vs 1.22 +/-
0.08 ppm; p = 0.002), showing that it was not caused by lipid breakthrough, and
that it matched the lactate signal seen in standard measurements (1.36 +/- 0.02
ppm). In the absence of lipid, similar lactate concentrations were measured by
the two methods (mean ratio DQ filtered/standard acquisition = 1.10 +/- 0.21). In
7/20 cases with measurable lactate, signal was not measureable in the standard
acquisition owing to lipid overlap but was quantified in the DQ-filtered
acquisition. Conversely, lactate was undetected in seven DQ-filtered acquisitions
but visible using the standard acquisition. In conclusion, the DQ filtering
method has proven robust in eliminating lipid and permits uncontaminated
measurement of lactate. This is important validation prior to use in tissues
outside the brain, which contain large amounts of lipid and which are often
susceptible to motion.
PMID- 27514008
TI - Trends in the characteristics, dose-limiting toxicities and efficacy of phase I
oncology trials: The Cancer Research UK experience.
AB - INTRODUCTION: Phase I oncology trials have evolved over the years, and these
changes could have implications for future studies and patients. METHODS: Adult
trials sponsored by Cancer Research UK Centre for Drug Development between 1995
and 2013 were analysed. Forty-nine trials were divided into two groups based on
the starting date for recruitment: 1995-2003 (24 trials, n = 603) and 2004-2013
(25 trials, n = 750) for comparative purposes. RESULTS: From 1995-2003 to 2004
2013, there was a shift towards studying non-cytotoxic agents that are
administered orally. In later trials, patients tended to have better performance
status, were older, had greater disease burden, and were more likely to have
received prior treatment. In 2004-2013, wider variety of dose escalation designs
were used, and studies were more likely to be multicentre, target/disease
specific, conducted in first-/any-line setting and to require tumour biopsy. The
overall incidence of dose-limiting toxicities (DLTs) was unchanged (10.9%; risk
of death 0.4%), but DLTs such as neuropathy, stomatitis and thrombocytopaenia
were less frequent in the more recent trials, while elevated liver enzymes were
more frequent. Non-classical DLTs emerged in the later trials, including
hypertension, hypophosphataemia, cardiac and ophthalmic toxicities. Disease
control rate (DCR) increased from 27.9% (1995-2003) to 36.0% (2004-2013; P =
0.0033) due to higher rates of disease stabilisation. CONCLUSION: Changes in
trial designs, therapeutic agents, patient characteristics and DLTs were
observed. Although the nature of DLTs changed, the incidence was similar in the
two time periods and DCR improved, suggesting that the benefit-risk balance for
patients participating in early-phase trials remains acceptable.
PMID- 27514009
TI - LPS injection reprograms the expression and the 3' UTR of a CAP gene by
alternative polyadenylation and the formation of a GAIT element in Ciona
intestinalis.
AB - The diversification of cellular functions is one of the major characteristics of
multicellular organisms which allow cells to modulate their gene expression,
leading to the formation of transcripts and proteins with different functions and
concentrations in response to different stimuli. CAP genes represent a widespread
family of proteins belonging to the cysteine-rich secretory protein, antigen 5
and pathogenesis-related 1 superfamily which, it has been proposed, play key
roles in the infection process and the modulation of immune responses in host
animals. The ascidian Ciona intestinalis represents a group of proto-chordates
with an exclusively innate immune system that has been widely studied in the
field of comparative and developmental immunology. Using this biological system,
we describe the identification of a novel APA mechanism by which an intronic
polyadenylation signal is activated by LPS injection, leading to the formation of
a shorter CAP mRNA capable of expressing the first CAP exon plus 19 amino acid
residues whose sequence is contained within the first intron of the annotated
gene. Furthermore, such an APA event causes the expression of a translational
controlling cis-acting GAIT element which is not present in the previously
isolated CAP isoform and identified in the 3'-UTR of other immune-related genes,
suggesting an intriguing scenario in which both transcriptional and post
transcriptional control mechanisms are involved in the activation of the CAP gene
during inflammatory response in C. intestinalis.
PMID- 27514010
TI - Severe Plasmodium vivax cerebral malaria complicated by hemophagocytic
lymphohistiocytosis treated with artesunate and doxycycline.
AB - Malaria-related hemophagocytic lymphohistiocytosis is a rare, potentially fatal,
hyperinflammatory disease entity which can be challenging to diagnose and treat.
It is usually associated with Plasmodium falciparum infection. It is less
frequently associated with Plasmodium vivax. Here we report an unusual case of a
23-year-old healthy Nigerian man who presented with fever, microangiopathic
hemolytic anemia, acute renal failure, and confusion, and was diagnosed as having
cerebral malaria-related hemophagocytic lymphohistiocytosis caused by P. vivax
infection. He was successfully treated with intravenous artesunate and
doxycycline with dramatic clinical improvement.
PMID- 27514011
TI - Mesenchymal stem cells in corneal neovascularization: Comparison of different
application routes.
AB - The purpose of the present study is to investigate the effect of mesenchymal stem
cells in corneal neovascularization and wound healing, and to compare the
effectiveness of two possible application routes, subconjunctival injection and
amniotic membrane transplantation. Chemical injury was induced by application of
sodium hydroxide to the rats' corneas. After 7 days, the animals were divided
into three groups. Different treatment methods were used for each group as
follows: i) Group 1, injection of bone marrow-derived mesenchymal stem cells
(BMSCs) under the conjunctiva; ii) group 2, transplantation of amniotic
membranes, previously seeded with BMSCs; and iii) group 3, the untreated control
group. The eyes were examined using a slit lamp on a weekly basis. After 4 weeks,
the animals were sacrificed and corneas were removed for further examination.
Corneal flat mounts were made following ink perfusion for improved vessel
visualization, image capturing and quantitative evaluation. enzyme-linked
immunosorbent assay was performed to detect the levels of vascular endothelial
growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9). Reverse
transcription-quantitative polymerase chain reaction was used for detection of
VEGF-A, MMP-9, Toll-like receptor (TLR)2 and TLR4 gene expression levels.
Cryosections were used for histological examination and immunostaining.
Statistical analysis (Welch's one-way analysis of variance) demonstrated a
significant difference between the groups [P<=0.05, confidence interval (CI)
95%]. The level of injury in group 1 was significantly different from groups 2
and 3. Measurement of the vessel area and VEGF gene expression levels had a
similar difference among the groups (P<=0.05, CI 95%), however the differences
for TLR2 and TLR4 were not statistically significant. BMSCs were previously
transduced with the green fluorescent protein gene by lentivirus to track the
movement of the cells following transplantation. The transplanted cells enhanced
corneal wound healing by trophic factor production and immune-regulatory effect,
rather than by direct transdifferentiation into corneal cells. The results of the
current study demonstrated that BMSCs enhance corneal wound healing and decrease
the area of neovascularization. Furthermore, the comparison of two application
routes indicated that single subconjunctival injection appeared more effective
than transplantation with amniotic membrane.
PMID- 27514012
TI - High impact of macroaggregated albumin-based tumour dose on response and overall
survival in hepatocellular carcinoma patients treated with 90 Y-loaded glass
microsphere radioembolization.
AB - BACKGROUND & AIMS: Efficacy of radioembolization is derived from radioinduced
damage, whereas tumour dosimetry is not considered as yet in prospective clinical
trials. OBJECTIVES: This study evaluates the impact of tumour dose (TD), based on
99m Tc macroaggregated albumin (MAA) quantification, on response and overall
survival (OS). MATERIALS AND METHODS: We consecutively included 85 patients with
hepatocellular carcinoma treated with 90 Y-loaded glass microspheres. TD was
calculated using a quantitative analysis of the MAA SPECT/CT. Responses were
assessed after 3 months using the European Association for the Study of the Liver
criteria. OS was assessed using Kaplan-Meier tests. RESULTS: Response rate was
80.3% on lesion-based analysis (n=132), and 77.5% on patient-based analysis. The
response rate was only 9.1% for patients with TD <205 Gy against 89.7% for those
with TD >=205 Gy (P<10-7 ). Non-portal vein thrombosis (PVT) patients exhibited a
median OS of 11.75 m (95% CI: 3-30.7 m) for TD <205 Gy, and 25 m (95% CI: 15-34.7
m) for TD >=205 Gy (P=.0391). PVT patients exhibited a 4.35 m median OS (95% CI:
2-8 m) for TD<205 Gy, and 15.7 m (95% CI: 9.5-25.5 m) for TD >=205 Gy, (P=.0004),
with HR of 6.99. PVT patients exhibited a median OS of 3.6 m (95% CI: 2-8 m) when
PVT MAA targeting was poor or with TD <205 Gy (poor candidate), vs 17.5 m (95%
CI: 11-26.5 m) for the others identified as good candidates (P<.0001), with HR of
12.85. CONCLUSION: This study confirms the highly predictive value of MAA-based
TD evaluation for response and OS. TD evaluation and PVT MAA targeting should be
further evaluated in ongoing trials, whereas personalized dosimetry should be
implemented in new trial designs.
PMID- 27514014
TI - Analysis of residual content of used syringes collected from low threshold
facilities in Lausanne, Switzerland.
AB - BACKGROUND: For the first time in Switzerland, an analysis of residual contents
from used syringes collected from low threshold facilities was performed. This
preliminary study is part of a wider project aiming to understand patterns of
injecting drug use over time. METHODS: Among the 100,000 syringes exchanged
annually by the ABS foundation (Accueil Bas Seuil), 113 were collected following
a purposive sampling method and analysed by gas chromatography coupled with mass
spectrometry (GC-MS). RESULTS: Four syringes (4% of the sample population)
contained no substances take into consideration the limit of the method. Cocaine
was the most commonly observed compound and was detected in 77 syringes (68%),
whilst users reported syringes with cocaine among those analysed in this study.
Heroin was detected in 49 syringes (43%) and reported by 53 users returning
syringes; midazolam was detected in 31 syringes (27%) and reported as the
medicine Dormicum((r)) in 22 occurrences. No new or unusual illicit drug was
detected in the sample. CONCLUSION: The results show the presence of cocaine in
more than half of the sample, an absence of new or unusual illicit drugs, as well
as very few traces of methadone, which suggests that this substitution drug is
rarely injected. This preliminary study also demonstrates the potential of this
developed methodology for monitoring purposes. An ongoing and more systematic
approach could allow to detect modifications in drug use patterns among the
target population as well as the appearance of new and hazardous substances. Such
systematic and timely results could allow an adaptation of harm reduction
interventions.
PMID- 27514013
TI - Long-term survival and regeneration of neuronal and vasculature cells inside the
core region after ischemic stroke in adult mice.
AB - Focal cerebral ischemia results in an ischemic core surrounded by the peri
infarct region (penumbra). Most research attention has been focused on penumbra
while the pattern of cell fates inside the ischemic core is poorly defined. In
the present investigation, we tested the hypothesis that, inside the ischemic
core, some neuronal and vascular cells could survive the initial ischemic insult
while regenerative niches might exist many days after stroke in the adult brain.
Adult mice were subjected to focal cerebral ischemia induced by permanent
occlusion of distal branches of the middle cerebral artery (MCA) plus transient
ligations of bilateral common carotid artery (CCA). The ischemic insult uniformly
reduced the local cerebral blood flow (LCBF) by 90%. Massive cell death occurred
due to multiple mechanisms and a significant infarction was cultivated in the
ischemic cortex 24 h later. Nevertheless, normal or even higher levels of brain
derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF)
persistently remained in the core tissue, some NeuN-positive and Glut-1/College
IV-positive cells with intact ultrastructural features resided in the core 7-14
days post stroke. BrdU-positive but TUNEL-negative neuronal and endothelial cells
were detected in the core where extensive extracellular matrix infrastructure
developed. Meanwhile, GFAP-positive astrocytes accumulated in the penumbra and
Iba-1-positive microglial/macrophages invaded the core several days after stroke.
The long term survival of neuronal and vascular cells inside the ischemic core
was also seen after a severe ischemic stroke induced by permanent embolic
occlusion of the MCA. We demonstrate that a therapeutic intervention of
pharmacological hypothermia could save neurons/endothelial cells inside the core.
These data suggest that the ischemic core is an actively regulated brain region
with residual and newly formed viable neuronal and vascular cells acutely and
chronically after at least some types of ischemic strokes.
PMID- 27514015
TI - Development of a novel immunoassay for herbal cannabis using a new fluorescent
antibody probe, "Ultra Quenchbody".
AB - We developed a novel immunoassay for herbal cannabis based on a new immunoassay
principle that uses Ultra Quenchbody ("UQ-body"), a recombinant antibody Fab
fragment fluorolabeled at the N-terminal regions. When the antigen binds to anti
Delta(9)-tetrahydrocannabinol (THC) UQ-body, the fluorescence intensity (FI)
decreases. The analytical conditions of the immunoassay were optimized based on
the FI reduction rate (FIRR). Following are the steps in the final analytical
procedure: (1) 10mg of samples were extracted with 1ml of a 60:40 mixture of
methanol and phosphate-buffered saline (PBS); (2) the extract was filtered
through a centrifugal 0.2-MUm polytetrafluoroethylene membrane filter; (3) the
filtrate was diluted 100 times with extraction solvent; (4) 6-MUl diluted
solution was mixed with 19-MUl PBS and 75-MUl UQ-body solution; and (5) FIRR was
measured under 275-mV excitation light. Herbal cannabis samples containing >=4.0
mg/g THC gave FIRRs of >=5.2%. FIRRs of negative samples (cigarette, tea, spice,
and so-called "synthetic marijuana") were <=3.1%. When setting the FIRR threshold
to 5.0%, cannabis samples containing >=4.0-mg/g THC were correctly judged as
positive without being affected by false positives caused by the negative
samples. This detection limit was lower than total THC level (10-200mg/g) in most
herbal cannabis samples seized in Japan. In seven of the 10 cannabis samples, the
results of the UQ-body test were comparable with those of the Duquenois-Levine
test. Thus, the UQ-body-based immunoassay is presumed to be an effective and
objective drug screening method for herbal cannabis; however, to show the true
usefulness, it is necessary to test a number of real case samples in the field
situation.
PMID- 27514016
TI - Elemental and molecular profiling of licit, illicit, and niche tobacco.
AB - The recognition of differences between regulated large-scale mass manufactured
products and the uncontrolled cultivation of tobaccos for illicit purposes plays
a significant role within identification of provenance. This research highlights
X-ray fluorescence and Fourier transform infrared spectroscopy as useful
analytical techniques for the rapid identification of tobacco samples of unknown
provenance. Identification of key discriminative features within each technique
allowed for the development of typical characteristic profiles for each type of
tobacco. Analysis using X-ray fluorescence highlights chlorine, potassium,
calcium and iron as key elemental indicators of tobacco provenance. Significant
levels of chlorine seen within Snus samples prompted attempts to visualise
chlorine containing regions and structures within the sample. Scanning electron
microscopy images showed crystalline structures visible within the Snus tobacco,
structures which Energy dispersive X-ray spectroscopy qualitatively confirmed to
contain chlorine. Chloride levels within Snus samples were quantified using ion
chromatography with levels found to range between 0.87mgmL(-1) and 1.28mg.
Additionally, FTIR indicated that absorbances attributed to carbonyl stretching
at 1050-1150cm(-1), alkane bending at 1350-1480cm(-1) and amide I stretching at
1600-1700cm(-1) highlighting a spectral fingerprint region that allowed for the
clear differentiation between different types of tobaccos using PCA analysis, but
was limited by differentiation between provenance of cigarettes and hand rolled
tobacco. X-ray fluorescence and Fourier transform infrared spectroscopy yielded
different information with regards tobacco discrimination and provenance, however
both methods overall analysis time and cost reduced indicating usefulness as
potential handheld analytical techniques in the field.
PMID- 27514017
TI - Effects of elevated carbon dioxide on stomatal characteristics and carbon isotope
ratio of Arabidopsis thaliana ecotypes originating from an altitudinal gradient.
AB - Stomatal functioning regulates the fluxes of CO2 and water vapor between
vegetation and atmosphere and thereby influences plant adaptation to their
habitats. Stomatal traits are controlled by external environmental and internal
cellular signaling. The objective of this study was to quantify the effects of
CO2 enrichment (CE) on stomatal density (SD)-related properties, guard cell
length (GCL) and carbon isotope ratio (delta13 C) of a range of Arabidopsis
thaliana ecotypes originating from a wide altitudinal range [50-1260 m above sea
level (asl)], and grown at 400 and 800 ppm [CO2 ], and thereby elucidate the
possible adaptation and acclimation responses controlling stomatal traits and
water use efficiency (WUE). There was a highly significant variation among
ecotypes in the magnitude and direction of response of stomatal traits namely, SD
and stomatal index (SI) and GCL, and delta13 C to CE, which represented a short
term acclimation response. A majority of ecotypes showed increased SD and SI with
CE with the response not depending on the altitude of origin. Significant
ecotypic variation was shown in all stomatal traits and delta13 C at each [CO2 ].
At 400 ppm, means of SD, SI and GCL for broad altitudinal ranges, i.e. low (<100
m), mid (100-400 m) and high (>400 m), increased with increasing altitude, which
represented an adaptation response to decreased availability of CO2 with
altitude. delta13 C was negatively correlated to SD and SI at 800 ppm but not at
400 ppm. Our results highlight the diversity in the response of key stomatal
characters to CE and altitude within the germplasm of A. thaliana and the need to
consider this diversity when using A. thaliana as a model plant.
PMID- 27514018
TI - Spatial and temporal dimensions of fire activity in the fire-prone eastern
Canadian taiga.
AB - The forest age mosaic is a fundamental attribute of the North American boreal
forest. Given that fires are generally lethal to trees, the time since last fire
largely determines the composition and structure of forest stands and landscapes.
Although the spatiotemporal dynamics of such mosaics has long been assumed to be
random under the overwhelming influence of severe fire weather, no long-term
reconstruction of mosaic dynamics has been performed from direct field evidence.
In this study, we use fire length as a proxy for fire extent across the fire
prone eastern Canadian taiga and systematically reconstruct the spatiotemporal
variability of fire extent and fire intervals, as well as the resulting forest
age along a 340-km transect for the 1840-2013 time period. Our results indicate
an extremely active fire regime over the last two centuries, with an overall burn
rate of 2.1% of the land area yr-1 , mainly triggered by seasonal anomalies of
high temperature and severe drought. However, the rejuvenation of the age mosaic
was strongly patterned in space and time due to the intrinsically lower burn
rates in wetland-dominated areas and, more importantly, to the much-reduced
likelihood of burning of stands up to 50 years postfire. An extremely high burn
rate of ~5% yr-1 would have characterized our study region during the last
century in the absence of such fuel age effect. Although recent burn rates and
fire sizes are within their range of variability of the last 175 years, a
particularly severe weather event allowed a 2013 fire to spread across a large
fire refuge, thus shifting the abundance of mature and old forest to a historic
low. These results provide reference conditions to evaluate the significance and
predict the spatiotemporal dynamics and impacts of the currently strengthening
fire activity in the North American boreal forest.
PMID- 27514019
TI - Consequences of coinfection with protective symbionts on the host phenotype and
symbiont titres in the pea aphid system.
AB - Symbiotic associations between microbes and insects are widespread, and it is
frequent that several symbionts share the same host individual. Hence,
interactions can occur between these symbionts, influencing their respective
abundance within the host with consequences on its phenotype. Here, we
investigate the effects of multiple infections in the pea aphid, Acyrthosiphon
pisum, which is the host of an obligatory and several facultative symbionts. In
particular, we study the influence of a coinfection with 2 protective symbionts:
Hamiltonella defensa, which confers protection against parasitoids, and
Rickettsiella viridis, which provides protection against fungal pathogens and
predators. The effects of Hamiltonella-Rickettsiella coinfection on the
respective abundance of the symbionts, host fitness and efficacy of enemy
protection were studied. Asymmetrical interactions between the 2 protective
symbionts have been found: when they coinfect the same aphid individuals, the
Rickettsiella infection affected Hamiltonella abundance within hosts but not the
Hamiltonella-mediated protective phenotype while the Hamiltonella infection
negatively influences the Rickettsiella-mediated protective phenotype but not its
abundance. Harboring the 2 protective symbionts also reduced the survival and
fecundity of host individuals. Overall, this work highlights the effects of
multiple infections on symbiont abundances and host traits that are likely to
impact the maintenance of the symbiotic associations in natural habitats.
PMID- 27514020
TI - Microbial elements as the initial triggers in the pathogenesis of polymorphic
light eruption?
AB - The primary trigger of polymorphic light eruption (PLE) remains to be uncovered.
We hypothesize that PLE may be initiated by elements resulting from UV-induced
damage to microbial communities of the skin, leading to a cascade of events
eventually resulting in the skin rash of the disease. One mechanism by which
epidermal injury by UV radiation could trigger PLE are danger signals such as
damage or pathogen associated molecular patterns DAMP/PAMPs or commensal
associated molecular patterns (CAMPs). Such triggers could be produced due to UV
induced stress on microbial communities of the skin and exacerbate inflammatory
responses by inducing the innate immune system through antimicrobial peptides
(AMPs) such as psoriasin, RNase7, HBD-2 and LL-37. These AMPs also actively take
part in initiating adaptive immunity. That signals derived from microbial rather
than human elements may initiate PLE is supported by series of observations,
including the PLE-protective effect of topically applied microbial-derived DNA
repair enzymes.
PMID- 27514021
TI - Dependence of thoracic fluid content with anthropometric-geometric factors in
impedance cardiography.
PMID- 27514022
TI - Tungsten(VI) Carbyne/Bis(carbene) Tautomerization Enabled by N-Donor SBA15
Surface Ligands: A Solid-State NMR and DFT Study.
AB - Designing supported well-defined bis(carbene) complexes remains a key challenge
in heterogeneous catalysis. The reaction of W(=CtBu)(CH2 tBu)3 with amine
modified mesoporous SBA15 silica, which has vicinal silanol/silylamine pairs
[(=SiOH)(=SiNH2 )], leads to [(=SiNH2 -)(=SiO-)W(=CHtBu)(CH2 tBu)2 ] and [(=SiNH2
-)(=SiO-)W(=CHtBu)2 (CH2 tBu). Variable temperature, (1) H-(1) H 2D double
quantum, (1) H-(13) C HETCOR, and HETCOR with spin diffusion solid-state NMR
spectroscopy demonstrate tautomerization between the alkyl alkylidyne and the
bis(alkylidene) on the SBA15 surface. Such equilibrium is possible through the
coordination of W to the surface [(=Si-OH)(=Si-NH2 )] groups, which act as a
[N,O] pincer ligand. DFT calculations provide a rationalization for the surface
complex tautomerization and support the experimental results. This direct
observation of such a process shows the strong similarity between molecular
mechanisms in homogeneous and heterogeneous catalysis. In propane metathesis (at
150 degrees C), the tungsten bis(carbene) tautomer is favorable, with a turnover
number (TON) of 262. It is the highest TON among all the tungsten alkyl-supported
catalysts.
PMID- 27514023
TI - MAP Kinase-Dependent RUNX2 Phosphorylation Is Necessary for Epigenetic
Modification of Chromatin During Osteoblast Differentiation.
AB - RUNX2, an essential transcription factor for osteoblast differentiation and bone
formation is activated by ERK/MAP kinase-dependent phosphorylation. However,
relationship between these early events and specific epigenetic modifications of
chromatin during osteoblast differentiation have not been previously examined.
Here, we explore these relationships using chromatin immunoprecipitation (ChIP)
to detect chromatin modifications in RUNX2-binding regions of Bglap2 and Ibsp.
Growth of MC3T3-E1c4 preosteoblast cells in differentiation conditions rapidly
induced Bglap2 and lbsp mRNAs. For both genes, osteogenic stimulation increased
chromatin-bound P-ERK, P-RUNX2, p300, and RNA polymerase II as well as histone
H3K9 and H4K5 acetylation. The level of H3K4 di-methylation, another gene
activation-associated histone mark, also increased. In contrast, levels of the
gene repressive marks, H3K9 mono-, di-, and tri-methylation in the same regions
were reduced. Inhibition of MAP kinase signaling blocked differentiation
dependent chromatin modifications and Bglap2 and Ibsp expression. To evaluate the
role of RUNX2 phosphorylation in these responses, RUNX2-deficient C3H10T1/2 cells
were transduced with adenovirus encoding wild type or phosphorylation site mutant
RUNX2 (RUNX2 S301A/S319A). Wild type RUNX2, but not the non-phosphorylated
mutant, increased H3K9 and H4K5 acetylation as well as chromatin-associated P
ERK, p300, and polymerase II. Thus, RUNX2 phosphorylation is necessary for
subsequent epigenetic changes required for osteoblast gene expression. Taken
together, this study reveals a molecular mechanism through which osteogenic genes
are controlled by a MAPK and P-RUNX2-dependent process involving epigenetic
modifications of specific promoter regions. J. Cell. Physiol. 232: 2427-2435,
2017. (c) 2016 Wiley Periodicals, Inc.
PMID- 27514024
TI - Dysregulated Wnt signalling and recurrent mutations of the tumour suppressor
RNF43 in early gastric carcinogenesis.
AB - Several recurrent mutations and epigenetic changes have been identified in
advanced gastric cancer, but the genetic alterations associated with early
gastric carcinogenesis and malignant transformation remain unclear. We
investigated the genomic and transcriptomic landscape of adenomas with low-grade
dysplasia (LGD) and high-grade dysplasia (HGD), and intestinal-type early gastric
cancer (EGC). The results were validated in an independent cohort that included
EGCs directly adjacent to adenoma (EGC-adenomas) that were in the process of
malignant transformation, and de novo EGCs that do not seem to have been derived
from adenoma. The expression patterns clearly divided into normal, LGD, and EGC,
whereas those of HGD overlapped with LGD or EGC. These results suggest that HGD
is the critical stage determining malignant transformation. We found that genes
related to focal adhesion and extracellular matrix receptor interaction pathways
were upregulated as LGD progressed to EGC, whereas canonical Wnt signalling and
peroxisome proliferator-activated receptor (PPAR) signalling pathway genes were
downregulated in EGC. Genomic alterations such as somatic mutation, gene fusion
and copy number variation increased gradually from LGD to EGC. APC mutations were
present in 67% of LGDs, 58% of HGDs, and 18% of EGCs. RNF43 mutations were
present only in HGD and EGC, and TP53 mutations were present only in EGC. In a
validation cohort, RNF43 mutations were present in 35.2% of EGC-adenomas, but in
only 8.6% of de novo EGCs. This is the first study to investigate the genomic and
transcriptomic landscape of multistep gastric carcinogenesis. We investigated
important alterations and their related pathways in each step as tumours
progressed from LGD to HGD and eventually to EGC. We suggest that mutations and
downregulation of RNF43 may play a critical role in the transition from adenoma
to carcinoma. Given these findings and Wnt dependency in tumours with RNF43
mutation, intestinal-type gastric cancer or adenoma with RNF43 mutation might
represent a promising indication for Wnt-targeted agents. Copyright (c) 2016
Pathological Society of Great Britain and Ireland. Published by John Wiley &
Sons, Ltd.
PMID- 27514025
TI - Conformational quiescence of ADAMTS-13 prevents proteolytic promiscuity.
AB - Essentials Recently, ADAMTS-13 has been shown to undergo substrate induced
conformation activation. Conformational quiescence of ADAMTS-13 may serve to
prevent off-target proteolysis in plasma. Conformationally active ADAMTS-13
variants are capable of proteolysing the Aalpha chain of fibrinogen. This should
be considered as ADAMTS-13 variants are developed as potential therapeutic
agents. Click to hear Dr Zheng's presentation on structure function and cofactor
dependent regulation of ADAMTS-13 SUMMARY: Background Recent work has revealed
that ADAMTS-13 circulates in a 'closed' conformation, only fully interacting with
von Willebrand factor (VWF) following a conformational change. We hypothesized
that this conformational quiescence also maintains the substrate specificity of
ADAMTS-13 and that the 'open' conformation of the protease might facilitate
proteolytic promiscuity. Objectives To identify a novel substrate for a
constitutively active gain of function (GoF) ADAMTS-13 variant
(R568K/F592Y/R660K/Y661F/Y665F). Methods Fibrinogen proteolysis was characterized
using SDS PAGE and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Fibrin formation was monitored by turbidity measurements and fibrin structure
visualized by confocal microscopy. Results ADAMTS-13 exhibits proteolytic
activity against the Aalpha chain of human fibrinogen, but this is only manifest
on its conformational activation. Accordingly, the GoF ADAMTS-13 variant and
truncated variants such as MDTCS exhibit this activity. The cleavage site has
been determined by LC-MS/MS to be Aalpha chain Lys225-Met226. Proteolysis of
fibrinogen by GoF ADAMTS-13 impairs fibrin formation in plasma-based assays,
alters clot structure and increases clot permeability. Although GoF ADAMTS-13
does not appear to proteolyse preformed cross-linked fibrin, its proteolytic
activity against fibrinogen increases the susceptibility of fibrin to tissue-type
plasminogen activator (t-PA)-induced lysis by plasmin and increases the fibrin
clearance rate more than 8-fold compared with wild-type (WT) ADAMTS-13 (EC50
values of 3.0 +/- 1.7 nm and 25.2 +/- 9.7 nm, respectively) in in vitro
thrombosis models. Conclusion The 'closed' conformation of ADAMTS-13 restricts
its specificity and protects against fibrinogenolysis. Induced substrate
promiscuity will be important as ADAMTS-13 variants are developed as potential
therapeutic agents against thrombotic thrombocytopenic purpura (TTP) and other
cardiovascular diseases.
PMID- 27514028
TI - Improvising in Three Dimensions.
AB - Lyle Hatch navigates 3D worlds and sometimes arrives at the surreal, regularly
producing an immense catalog of imagery. With Mandelbulb 3D as his creative
environment of choice, Hatch generates seemingly endless amounts of evocative and
colorful imagery.
PMID- 27514029
TI - Topic- and Time-Oriented Visual Text Analysis.
AB - To facilitate the process of converting textual data into actionable knowledge,
visual text analysis has become a popular topic with active research efforts
contributed by researchers worldwide. Here the authors present the benefits of
combing text analysis (topic models in particular) with interactive
visualization. They then highlight examples from prior work on topic- and time
oriented visual text analysis and discuss challenges that warrant additional
future research.
PMID- 27514026
TI - The composition and organization of Drosophila heterochromatin are heterogeneous
and dynamic.
AB - Heterochromatin is enriched for specific epigenetic factors including
Heterochromatin Protein 1a (HP1a), and is essential for many organismal
functions. To elucidate heterochromatin organization and regulation, we purified
Drosophila melanogaster HP1a interactors, and performed a genome-wide RNAi screen
to identify genes that impact HP1a levels or localization. The majority of the
over four hundred putative HP1a interactors and regulators identified were
previously unknown. We found that 13 of 16 tested candidates (83%) are required
for gene silencing, providing a substantial increase in the number of identified
components that impact heterochromatin properties. Surprisingly, image analysis
revealed that although some HP1a interactors and regulators are broadly
distributed within the heterochromatin domain, most localize to discrete
subdomains that display dynamic localization patterns during the cell cycle. We
conclude that heterochromatin composition and architecture is more spatially
complex and dynamic than previously suggested, and propose that a network of
subdomains regulates diverse heterochromatin functions.
PMID- 27514027
TI - Epigenetic gene regulation by histone demethylases: emerging role in oncogenesis
and inflammation.
AB - Histone N-terminal tails of nucleosomes are the sites of complex regulation of
gene expression through post-translational modifications. Among these
modifications, histone methylation had long been associated with permanent gene
inactivation until the discovery of Lys-specific demethylase (LSD1), which is
responsible for dynamic gene regulation. There are more than 30 members of the
Lys demethylase (KDM) family, and with exception of LSD1 and LSD2, all other KDMs
possess the Jumonji C (JmjC) domain exhibiting demethylase activity and require
unique cofactors, for example, Fe(II) and alpha-ketoglutarate. These cofactors
have been targeted when devising KDM inhibitors, which may yield therapeutic
benefit. KDMs and their counterpart Lys methyltransferases (KMTs) regulate
multiple biological processes, including oncogenesis and inflammation. KDMs'
functional interactions with retinoblastoma (Rb) and E2 factor (E2F) target
promoters illustrate their regulatory role in cell cycle progression and
oncogenesis. Recent findings also demonstrate the control of inflammation and
immune functions by KDMs, such as KDM6B that regulates the pro-inflammatory gene
expression and CD4+ T helper (Th) cell lineage determination. This review will
highlight the mechanisms by which KDMs and KMTs regulate the target gene
expression and how epigenetic mechanisms may be applied to our understanding of
oral inflammation.
PMID- 27514030
TI - Precision Agriculture: Using Low-Cost Systems to Acquire Low-Altitude Images.
AB - Low cost remote sensing imagery has the potential to make precision farming
feasible in developing countries. In this article, the authors describe image
acquisition from eucalyptus, bean, and sugarcane crops acquired by low-cost and
low-altitude systems. They use different approaches to handle low-altitude images
in both the RGB and NIR (near-infrared) bands to estimate and quantify plantation
areas.
PMID- 27514031
TI - Predicting Moves-on-Stills for Comic Art Using Viewer Gaze Data.
AB - Comic art consists of a sequence of panels of different shapes and sizes that
visually communicate the narrative to the reader. The move-on-stills technique
allows such still images to be retargeted for digital displays via camera moves.
Today, moves-on-stills can be created by software applications given user
provided parameters for each desired camera move. The proposed algorithm uses
viewer gaze as input to computationally predict camera move parameters. The
authors demonstrate their algorithm on various comic book panels and evaluate its
performance by comparing their results with a professional DVD.
PMID- 27514032
TI - Designing for Insight: A Case Study from Tennis Player Analysis.
AB - Visualization is an important tool, necessary for making sense of vast amounts of
data. Many data science projects make use of visualization techniques to
illustrate and explain their results. But complex interactive visualizations can
also be excellent exploration tools to help guide the analysis, detect early
signs of problems and irregularities, suggest new discoveries, and test the
effectiveness and efficiency of scientific models. This article describes a
combinatory design process that uses a method of incremental addition to create
increasingly complex arrangements and thus create new ways to see data and
discover new insights.
PMID- 27514034
TI - City-Scale Localization for Cameras with Known Vertical Direction.
AB - We consider the problem of localizing a novel image in a large 3D model, given
that the gravitational vector is known. In principle, this is just an instance of
camera pose estimation, but the scale of the problem introduces some interesting
challenges. Most importantly, it makes the correspondence problem very difficult
so there will often be a significant number of outliers to handle. To tackle this
problem, we use recent theoretical as well as technical advances. Many modern
cameras and phones have gravitational sensors that allow us to reduce the search
space. Further, there are new techniques to efficiently and reliably deal with
extreme rates of outliers. We extend these methods to camera pose estimation by
using accurate approximations and fast polynomial solvers. Experimental results
are given demonstrating that it is possible to reliably estimate the camera pose
despite cases with more than 99 percent outlier correspondences in city-scale
models with several millions of 3D points.
PMID- 27514035
TI - A Novel Nonparametric Maximum Likelihood Estimator for Probability Density
Functions.
AB - Parametric maximum likelihood (ML) estimators of probability density functions
(pdfs) are widely used today because they are efficient to compute and have
several nice properties such as consistency, fast convergence rates, and
asymptotic normality. However, data is often complex making parametrization of
the pdf difficult, and nonparametric estimation is required. Popular
nonparametric methods, such as kernel density estimation (KDE), produce
consistent estimators but are not ML and have slower convergence rates than
parametric ML estimators. Further, these nonparametric methods do not share the
other desirable properties of parametric ML estimators. This paper introduces a
nonparametric ML estimator that assumes that the square-root of the underlying
pdf is band-limited (BL) and hence "smooth". The BLML estimator is computed and
shown to be consistent. Although convergence rates are not theoretically derived,
the BLML estimator exhibits faster convergence rates than state-of-the-art
nonparametric methods in simulations. Further, algorithms to compute the BLML
estimator with lesser computational complexity than that of KDE methods are
presented. The efficacy of the BLML estimator is shown by applying it to (i)
density tail estimation and (ii) density estimation of complex neuronal receptive
fields where it outperforms state-of-the-art methods used in neuroscience.
PMID- 27514036
TI - Deep Visual-Semantic Alignments for Generating Image Descriptions.
AB - We present a model that generates natural language descriptions of images and
their regions. Our approach leverages datasets of images and their sentence
descriptions to learn about the inter-modal correspondences between language and
visual data. Our alignment model is based on a novel combination of Convolutional
Neural Networks over image regions, bidirectional Recurrent Neural Networks (RNN)
over sentences, and a structured objective that aligns the two modalities through
a multimodal embedding. We then describe a Multimodal Recurrent Neural Network
architecture that uses the inferred alignments to learn to generate novel
descriptions of image regions. We demonstrate that our alignment model produces
state of the art results in retrieval experiments on Flickr8K, Flickr30K and
MSCOCO datasets. We then show that the generated descriptions outperform
retrieval baselines on both full images and on a new dataset of region-level
annotations. Finally, we conduct large-scale analysis of our RNN language model
on the Visual Genome dataset of 4.1 million captions and highlight the
differences between image and region-level caption statistics.
PMID- 27514037
TI - Learning to Segment Human by Watching YouTube.
AB - An intuition on human segmentation is that when a human is moving in a video, the
video-context (e.g., appearance and motion clues) may potentially infer
reasonable mask information for the whole human body. Inspired by this, based on
popular deep convolutional neural networks (CNN), we explore a very-weakly
supervised learning framework for human segmentation task, where only an
imperfect human detector is available along with massive weakly-labeled YouTube
videos. In our solution, the video-context guided human mask inference and CNN
based segmentation network learning iterate to mutually enhance each other until
no further improvement gains. In the first step, each video is decomposed into
supervoxels by the unsupervised video segmentation. The superpixels within the
supervoxels are then classified as human or non-human by graph optimization with
unary energies from the imperfect human detection results and the predicted
confidence maps by the CNN trained in the previous iteration. In the second step,
the video-context derived human masks are used as direct labels to train CNN.
Extensive experiments on the challenging PASCAL VOC 2012 semantic segmentation
benchmark demonstrate that the proposed framework has already achieved superior
results than all previous weakly-supervised methods with object class or bounding
box annotations. In addition, by augmenting with the annotated masks from PASCAL
VOC 2012, our method reaches a new state-of-the-art performance on the human
segmentation task.
PMID- 27514038
TI - Randomly Perturbed B-Splines for Nonrigid Image Registration.
AB - B-splines are commonly utilized to construct the transformation model in free
form deformation (FFD) based registration. B-splines become smoother with
increasing spline order. However, a higher-order B-spline requires a larger
support region involving more control points, which means higher computational
cost. In general, the third-order B-spline is considered as a good compromise
between spline smoothness and computational cost. A lower-order function is
seldom used to construct the transformation model for registration since it is
less smooth. In this research, we investigated whether lower-order B-spline
functions can be utilized for more efficient registration, while preserving
smoothness of the deformation by using a novel random perturbation technique.
With the proposed perturbation technique, the expected value of the cost function
given probability density function (PDF) of the perturbation is minimized by a
stochastic gradient descent optimization. Extensive experiments on 2D
synthetically deformed brain images, and real 3D lung and brain scans
demonstrated that the novel randomly perturbed free-form deformation (RPFFD)
approach improves the registration accuracy and transformation smoothness.
Meanwhile, lower-order RPFFD methods reduce the computational cost substantially.
PMID- 27514039
TI - Robust Retinal Vessel Segmentation via Locally Adaptive Derivative Frames in
Orientation Scores.
AB - This paper presents a robust and fully automatic filter-based approach for
retinal vessel segmentation. We propose new filters based on 3D rotating frames
in so-called orientation scores, which are functions on the Lie-group domain of
positions and orientations [Formula: see text]. By means of a wavelet-type
transform, a 2D image is lifted to a 3D orientation score, where elongated
structures are disentangled into their corresponding orientation planes. In the
lifted domain [Formula: see text], vessels are enhanced by means of multi-scale
second-order Gaussian derivatives perpendicular to the line structures. More
precisely, we use a left-invariant rotating derivative (LID) frame, and a locally
adaptive derivative (LAD) frame. The LAD is adaptive to the local line structures
and is found by eigensystem analysis of the left-invariant Hessian matrix
(computed with the LID). After multi-scale filtering via the LID or LAD in the
orientation score domain, the results are projected back to the 2D image plane
giving us the enhanced vessels. Then a binary segmentation is obtained through
thresholding. The proposed methods are validated on six retinal image datasets
with different image types, on which competitive segmentation performances are
achieved. In particular, the proposed algorithm of applying the LAD filter on
orientation scores (LAD-OS) outperforms most of the state-of-the-art methods. The
LAD-OS is capable of dealing with typically difficult cases like crossings,
central arterial reflex, closely parallel and tiny vessels. The high
computational speed of the proposed methods allows processing of large datasets
in a screening setting.
PMID- 27514041
TI - Generating Multi-Destination Maps.
AB - Multi-destination maps are a kind of navigation maps aimed to guide visitors to
multiple destinations within a region, which can be of great help to urban
visitors. However, they have not been developed in the current online map
service. To address this issue, we introduce a novel layout model designed
especially for generating multi-destination maps, which considers the global and
local layout of a multi-destination map. We model the layout problem as a graph
drawing that satisfies a set of hard and soft constraints. In the global layout
phase, we balance the scale factor between ROIs. In the local layout phase, we
make all edges have good visibility and optimize the map layout to preserve the
relative length and angle of roads. We also propose a perturbation-based
optimization method to find an optimal layout in the complex solution space. The
multi-destination maps generated by our system are potential feasible on the
modern mobile devices and our result can show an overview and a detail view of
the whole map at the same time. In addition, we perform a user study to evaluate
the effectiveness of our method, and the results prove that the multi-destination
maps achieve our goals well.
PMID- 27514042
TI - Shape Synthesis from Sketches via Procedural Models and Convolutional Networks.
AB - Procedural modeling techniques can produce high quality visual content through
complex rule sets. However, controlling the outputs of these techniques for
design purposes is often notoriously difficult for users due to the large number
of parameters involved in these rule sets and also their non-linear relationship
to the resulting content. To circumvent this problem, we present a sketch-based
approach to procedural modeling. Given an approximate and abstract hand-drawn 2D
sketch provided by a user, our algorithm automatically computes a set of
procedural model parameters, which in turn yield multiple, detailed output shapes
that resemble the user's input sketch. The user can then select an output shape,
or further modify the sketch to explore alternative ones. At the heart of our
approach is a deep Convolutional Neural Network (CNN) that is trained to map
sketches to procedural model parameters. The network is trained by large amounts
of automatically generated synthetic line drawings. By using an intuitive medium,
i.e., freehand sketching as input, users are set free from manually adjusting
procedural model parameters, yet they are still able to create high quality
content. We demonstrate the accuracy and efficacy of our method in a variety of
procedural modeling scenarios including design of man-made and organic shapes.
PMID- 27514043
TI - A Visual Analytics Approach for Understanding Reasons behind Snowballing and
Comeback in MOBA Games.
AB - To design a successful Multiplayer Online Battle Arena (MOBA) game, the ratio of
snowballing and comeback occurrences to all matches played must be maintained at
a certain level to ensure its fairness and engagement. Although it is easy to
identify these two types of occurrences, game developers often find it difficult
to determine their causes and triggers with so many game design choices and game
parameters involved. In addition, the huge amounts of MOBA game data are often
heterogeneous, multi-dimensional and highly dynamic in terms of space and time,
which poses special challenges for analysts. In this paper, we present a visual
analytics system to help game designers find key events and game parameters
resulting in snowballing or comeback occurrences in MOBA game data. We follow a
user-centered design process developing the system with game analysts and testing
with real data of a trial version MOBA game from NetEase Inc. We apply novel
visualization techniques in conjunction with well-established ones to depict the
evolution of players' positions, status and the occurrences of events. Our system
can reveal players' strategies and performance throughout a single match and
suggest patterns, e.g., specific player' actions and game events, that have led
to the final occurrences. We further demonstrate a workflow of leveraging human
analyzed patterns to improve the scalability and generality of match data
analysis. Finally, we validate the usability of our system by proving the
identified patterns are representative in snowballing or comeback matches in a
one-month-long MOBA tournament dataset.
PMID- 27514044
TI - SemanticTraj: A New Approach to Interacting with Massive Taxi Trajectories.
AB - Massive taxi trajectory data is exploited for knowledge discovery in
transportation and urban planning. Existing tools typically require users to
select and brush geospatial regions on a map when retrieving and exploring taxi
trajectories and passenger trips. To answer seemingly simple questions such as
"What were the taxi trips starting from Main Street and ending at Wall Street in
the morning?" or "Where are the taxis arriving at the Art Museum at noon
typically coming from?", tedious and time consuming interactions are usually
needed since the numeric GPS points of trajectories are not directly linked to
the keywords such as "Main Street", "Wall Street", and "Art Museum". In this
paper, we present SemanticTraj, a new method for managing and visualizing taxi
trajectory data in an intuitive, semantic rich, and efficient means. With
SemanticTraj, domain and public users can find answers to the aforementioned
questions easily through direct queries based on the terms. They can also
interactively explore the retrieved data in visualizations enhanced by semantic
information of the trajectories and trips. In particular, taxi trajectories are
converted into taxi documents through a textualization transformation process.
This process maps GPS points into a series of street/POI names and pick-up/drop
off locations. It also converts vehicle speeds into user-defined descriptive
terms. Then, a corpus of taxi documents is formed and indexed to enable flexible
semantic queries over a text search engine. Semantic labels and meta-summaries of
the results are integrated with a set of visualizations in a SemanticTraj
prototype, which helps users study taxi trajectories quickly and easily. A set of
usage scenarios are presented to show the usability of the system. We also
collected feedback from domain experts and conducted a preliminary user study to
evaluate the visual system.
PMID- 27514045
TI - Correlated Photon Mapping for Interactive Global Illumination of Time-Varying
Volumetric Data.
AB - We present a method for interactive global illumination of both static and time
varying volumetric data based on reduction of the overhead associated with re
computation of photon maps. Our method uses the identification of photon traces
invariant to changes of visual parameters such as the transfer function (TF), or
data changes between time-steps in a 4D volume. This lets us operate on a variant
subset of the entire photon distribution. The amount of computation required in
the two stages of the photon mapping process, namely tracing and gathering, can
thus be reduced to the subset that are affected by a data or visual parameter
change. We rely on two different types of information from the original data to
identify the regions that have changed. A low resolution uniform grid containing
the minimum and maximum data values of the original data is derived for each time
step. Similarly, for two consecutive time-steps, a low resolution grid containing
the difference between the overlapping data is used. We show that this compact
metadata can be combined with the transfer function to identify the regions that
have changed. Each photon traverses the low-resolution grid to identify if it can
be directly transferred to the next photon distribution state or if it needs to
be recomputed. An efficient representation of the photon distribution is
presented leading to an order of magnitude improved performance of the raycasting
step. The utility of the method is demonstrated in several examples that show
visual fidelity, as well as performance. The examples show that visual quality
can be retained when the fraction of retraced photons is as low as 40%-50%.
PMID- 27514046
TI - SmartAdP: Visual Analytics of Large-scale Taxi Trajectories for Selecting
Billboard Locations.
AB - The problem of formulating solutions immediately and comparing them rapidly for
billboard placements has plagued advertising planners for a long time, owing to
the lack of efficient tools for in-depth analyses to make informed decisions. In
this study, we attempt to employ visual analytics that combines the state-of-the
art mining and visualization techniques to tackle this problem using large-scale
GPS trajectory data. In particular, we present SmartAdP, an interactive visual
analytics system that deals with the two major challenges including finding good
solutions in a huge solution space and comparing the solutions in a visual and
intuitive manner. An interactive framework that integrates a novel visualization
driven data mining model enables advertising planners to effectively and
efficiently formulate good candidate solutions. In addition, we propose a set of
coupled visualizations: a solution view with metaphor-based glyphs to visualize
the correlation between different solutions; a location view to display billboard
locations in a compact manner; and a ranking view to present multi-typed rankings
of the solutions. This system has been demonstrated using case studies with a
real-world dataset and domain-expert interviews. Our approach can be adapted for
other location selection problems such as selecting locations of retail stores or
restaurants using trajectory data.
PMID- 27514047
TI - Visual Analysis of MOOC Forums with iForum.
AB - Discussion forums of Massive Open Online Courses (MOOC) provide great
opportunities for students to interact with instructional staff as well as other
students. Exploration of MOOC forum data can offer valuable insights for these
staff to enhance the course and prepare the next release. However, it is
challenging due to the large, complicated, and heterogeneous nature of relevant
datasets, which contain multiple dynamically interacting objects such as users,
posts, and threads, each one including multiple attributes. In this paper, we
present a design study for developing an interactive visual analytics system,
called iForum, that allows for effectively discovering and understanding temporal
patterns in MOOC forums. The design study was conducted with three domain experts
in an iterative manner over one year, including a MOOC instructor and two
official teaching assistants. iForum offers a set of novel visualization designs
for presenting the three interleaving aspects of MOOC forums (i.e., posts, users,
and threads) at three different scales. To demonstrate the effectiveness and
usefulness of iForum, we describe a case study involving field experts, in which
they use iForum to investigate real MOOC forum data for a course on JAVA
programming.
PMID- 27514048
TI - AxiSketcher: Interactive Nonlinear Axis Mapping of Visualizations through User
Drawings.
AB - Visual analytics techniques help users explore high-dimensional data. However, it
is often challenging for users to express their domain knowledge in order to
steer the underlying data model, especially when they have little attribute-level
knowledge. Furthermore, users' complex, high-level domain knowledge, compared to
low-level attributes, posits even greater challenges. To overcome these
challenges, we introduce a technique to interpret a user's drawings with an
interactive, nonlinear axis mapping approach called AxiSketcher. This technique
enables users to impose their domain knowledge on a visualization by allowing
interaction with data entries rather than with data attributes. The proposed
interaction is performed through directly sketching lines over the visualization.
Using this technique, users can draw lines over selected data points, and the
system forms the axes that represent a nonlinear, weighted combination of
multidimensional attributes. In this paper, we describe our techniques in three
areas: 1) the design space of sketching methods for eliciting users' nonlinear
domain knowledge; 2) the underlying model that translates users' input, extracts
patterns behind the selected data points, and results in nonlinear axes
reflecting users' complex intent; and 3) the interactive visualization for
viewing, assessing, and reconstructing the newly formed, nonlinear axes.
PMID- 27514049
TI - Toward Theoretical Techniques for Measuring the Use of Human Effort in Visual
Analytic Systems.
AB - Visual analytic systems have long relied on user studies and standard datasets to
demonstrate advances to the state of the art, as well as to illustrate the
efficiency of solutions to domain-specific challenges. This approach has enabled
some important comparisons between systems, but unfortunately the narrow scope
required to facilitate these comparisons has prevented many of these lessons from
being generalized to new areas. At the same time, advanced visual analytic
systems have made increasing use of human-machine collaboration to solve problems
not tractable by machine computation alone. To continue to make progress in
modeling user tasks in these hybrid visual analytic systems, we must strive to
gain insight into what makes certain tasks more complex than others. This will
require the development of mechanisms for describing the balance to be struck
between machine and human strengths with respect to analytical tasks and
workload. In this paper, we argue for the necessity of theoretical tools for
reasoning about such balance in visual analytic systems and demonstrate the
utility of the Human Oracle Model for this purpose in the context of sensemaking
in visual analytics. Additionally, we make use of the Human Oracle Model to guide
the development of a new system through a case study in the domain of
cybersecurity.
PMID- 27514050
TI - AnaFe: Visual Analytics of Image-derived Temporal Features-Focusing on the
Spleen.
AB - We present a novel visualization framework, AnaFe, targeted at observing changes
in the spleen over time through multiple image-derived features. Accurate
monitoring of progressive changes is crucial for diseases that result in
enlargement of the organ. Our system is comprised of multiple linked views
combining visualization of temporal 3D organ data, related measurements, and
features. Thus it enables the observation of progression and allows for
simultaneous comparison within and between the subjects. AnaFe offers insights
into the overall distribution of robustly extracted and reproducible quantitative
imaging features and their changes within the population, and also enables
detailed analysis of individual cases. It performs similarity comparison of
temporal series of one subject to all other series in both sick and healthy
groups. We demonstrate our system through two use case scenarios on a population
of 189 spleen datasets from 68 subjects with various conditions observed over
time.
PMID- 27514051
TI - NameClarifier: A Visual Analytics System for Author Name Disambiguation.
AB - In this paper, we present a novel visual analytics system called NameClarifier to
interactively disambiguate author names in publications by keeping humans in the
loop. Specifically, NameClarifier quantifies and visualizes the similarities
between ambiguous names and those that have been confirmed in digital libraries.
The similarities are calculated using three key factors, namely, co-authorships,
publication venues, and temporal information. Our system estimates all possible
allocations, and then provides visual cues to users to help them validate every
ambiguous case. By looping users in the disambiguation process, our system can
achieve more reliable results than general data mining models for highly
ambiguous cases. In addition, once an ambiguous case is resolved, the result is
instantly added back to our system and serves as additional cues for all the
remaining unidentified names. In this way, we open up the black box in
traditional disambiguation processes, and help intuitively and comprehensively
explain why the corresponding classifications should hold. We conducted two use
cases and an expert review to demonstrate the effectiveness of NameClarifier.
PMID- 27514052
TI - Visualizing Dimension Coverage to Support Exploratory Analysis.
AB - Data analysis involves constantly formulating and testing new hypotheses and
questions about data. When dealing with a new dataset, especially one with many
dimensions, it can be cumbersome for the analyst to clearly remember which
aspects of the data have been investigated (i.e., visually examined for patterns,
trends, outliers etc.) and which combinations have not. Yet this information is
critical to help the analyst formulate new questions that they have not already
answered. We observe that for tabular data, questions are typically comprised of
varying combinations of data dimensions (e.g., what are the trends of Sales and
Profit for different Regions?). We propose representing analysis history from the
angle of dimension coverage (i.e., which data dimensions have been investigated
and in which combinations). We use scented widgets [30] to incorporate dimension
coverage of the analysts' past work into interaction widgets of a visualization
tool. We demonstrate how this approach can assist analysts with the question
formation process. Our approach extends the concept of scented widgets to reveal
aspects of one's own analysis history, and offers a different perspective on
one's past work than typical visualization history tools. Results of our
empirical study showed that participants with access to embedded dimension
coverage information relied on this information when formulating questions, asked
more questions about the data, generated more top-level findings, and showed
greater breadth of their analysis without sacrificing depth.
PMID- 27514053
TI - Magnostics: Image-Based Search of Interesting Matrix Views for Guided Network
Exploration.
AB - In this work we address the problem of retrieving potentially interesting matrix
views to support the exploration of networks. We introduce Matrix Diagnostics (or
Magnostics), following in spirit related approaches for rating and ranking other
visualization techniques, such as Scagnostics for scatter plots. Our approach
ranks matrix views according to the appearance of specific visual patterns, such
as blocks and lines, indicating the existence of topological motifs in the data,
such as clusters, bi-graphs, or central nodes. Magnostics can be used to analyze,
query, or search for visually similar matrices in large collections, or to assess
the quality of matrix reordering algorithms. While many feature descriptors for
image analyzes exist, there is no evidence how they perform for detecting
patterns in matrices. In order to make an informed choice of feature descriptors
for matrix diagnostics, we evaluate 30 feature descriptors-27 existing ones and
three new descriptors that we designed specifically for MAGNOSTICS-with respect
to four criteria: pattern response, pattern variability, pattern sensibility, and
pattern discrimination. We conclude with an informed set of six descriptors as
most appropriate for Magnostics and demonstrate their application in two
scenarios; exploring a large collection of matrices and analyzing temporal
networks.
PMID- 27514054
TI - Characterizing Guidance in Visual Analytics.
AB - Visual analytics (VA) is typically applied in scenarios where complex data has to
be analyzed. Unfortunately, there is a natural correlation between the complexity
of the data and the complexity of the tools to study them. An adverse effect of
complicated tools is that analytical goals are more difficult to reach.
Therefore, it makes sense to consider methods that guide or assist users in the
visual analysis process. Several such methods already exist in the literature,
yet we are lacking a general model that facilitates in-depth reasoning about
guidance. We establish such a model by extending van Wijk's model of
visualization with the fundamental components of guidance. Guidance is defined as
a process that gradually narrows the gap that hinders effective continuation of
the data analysis. We describe diverse inputs based on which guidance can be
generated and discuss different degrees of guidance and means to incorporate
guidance into VA tools. We use existing guidance approaches from the literature
to illustrate the various aspects of our model. As a conclusion, we identify
research challenges and suggest directions for future studies. With our work we
take a necessary step to pave the way to a systematic development of guidance
techniques that effectively support users in the context of VA.
PMID- 27514055
TI - PhenoStacks: Cross-Sectional Cohort Phenotype Comparison Visualizations.
AB - Cross-sectional phenotype studies are used by genetics researchers to better
understand how phenotypes vary across patients with genetic diseases, both within
and between cohorts. Analyses within cohorts identify patterns between phenotypes
and patients (e.g., co-occurrence) and isolate special cases (e.g., potential
outliers). Comparing the variation of phenotypes between two cohorts can help
distinguish how different factors affect disease manifestation (e.g., causal
genes, age of onset, etc.). PhenoStacks is a novel visual analytics tool that
supports the exploration of phenotype variation within and between cross
sectional patient cohorts. By leveraging the semantic hierarchy of the Human
Phenotype Ontology, phenotypes are presented in context, can be grouped and
clustered, and are summarized via overviews to support the exploration of
phenotype distributions. The design of PhenoStacks was motivated by formative
interviews with genetics researchers: we distil high-level tasks, present an
algorithm for simplifying ontology topologies for visualization, and report the
results of a deployment evaluation with four expert genetics researchers. The
results suggest that PhenoStacks can help identify phenotype patterns,
investigate data quality issues, and inform data collection design.
PMID- 27514056
TI - Designing Progressive and Interactive Analytics Processes for High-Dimensional
Data Analysis.
AB - In interactive data analysis processes, the dialogue between the human and the
computer is the enabling mechanism that can lead to actionable observations about
the phenomena being investigated. It is of paramount importance that this
dialogue is not interrupted by slow computational mechanisms that do not consider
any known temporal human-computer interaction characteristics that prioritize the
perceptual and cognitive capabilities of the users. In cases where the analysis
involves an integrated computational method, for instance to reduce the
dimensionality of the data or to perform clustering, such non-optimal processes
are often likely. To remedy this, progressive computations, where results are
iteratively improved, are getting increasing interest in visual analytics. In
this paper, we present techniques and design considerations to incorporate
progressive methods within interactive analysis processes that involve high
dimensional data. We define methodologies to facilitate processes that adhere to
the perceptual characteristics of users and describe how online algorithms can be
incorporated within these. A set of design recommendations and according methods
to support analysts in accomplishing high-dimensional data analysis tasks are
then presented. Our arguments and decisions here are informed by observations
gathered over a series of analysis sessions with analysts from finance. We
document observations and recommendations from this study and present evidence on
how our approach contribute to the efficiency and productivity of interactive
visual analysis sessions involving high-dimensional data.
PMID- 27514057
TI - A Grammar-based Approach for Modeling User Interactions and Generating
Suggestions During the Data Exploration Process.
AB - Despite the recent popularity of visual analytics focusing on big data, little is
known about how to support users that use visualization techniques to explore
multi-dimensional datasets and accomplish specific tasks. Our lack of models that
can assist end-users during the data exploration process has made it challenging
to learn from the user's interactive and analytical process. The ability to model
how a user interacts with a specific visualization technique and what
difficulties they face are paramount in supporting individuals with discovering
new patterns within their complex datasets. This paper introduces the notion of
visualization systems understanding and modeling user interactions with the
intent of guiding a user through a task thereby enhancing visual data
exploration. The challenges faced and the necessary future steps to take are
discussed; and to provide a working example, a grammar-based model is presented
that can learn from user interactions, determine the common patterns among a
number of subjects using a K-Reversible algorithm, build a set of rules, and
apply those rules in the form of suggestions to new users with the goal of
guiding them along their visual analytic process. A formal evaluation study with
300 subjects was performed showing that our grammar-based model is effective at
capturing the interactive process followed by users and that further research in
this area has the potential to positively impact how users interact with a
visualization system.
PMID- 27514059
TI - A Visual Analytics Approach for Categorical Joint Distribution Reconstruction
from Marginal Projections.
AB - Oftentimes multivariate data are not available as sets of equally multivariate
tuples, but only as sets of projections into subspaces spanned by subsets of
these attributes. For example, one may find data with five attributes stored in
six tables of two attributes each, instead of a single table of five attributes.
This prohibits the visualization of these data with standard high-dimensional
methods, such as parallel coordinates or MDS, and there is hence the need to
reconstruct the full multivariate (joint) distribution from these marginal ones.
Most of the existing methods designed for this purpose use an iterative procedure
to estimate the joint distribution. With insufficient marginal distributions and
domain knowledge, they lead to results whose joint errors can be large. Moreover,
enforcing smoothness for regularizations in the joint space is not applicable if
the attributes are not numerical but categorical. We propose a visual analytics
approach that integrates both anecdotal data and human experts to iteratively
narrow down a large set of plausible solutions. The solution space is populated
using a Monte Carlo procedure which uniformly samples the solution space. A level
of-detail high dimensional visualization system helps the user understand the
patterns and the uncertainties. Constraints that narrow the solution space can
then be added by the user interactively during the iterative exploration, and
eventually a subset of solutions with narrow uncertainty intervals emerges.
PMID- 27514058
TI - Blockwise Human Brain Network Visual Comparison Using NodeTrix Representation.
AB - Visually comparing human brain networks from multiple population groups serves as
an important task in the field of brain connectomics. The commonly used brain
network representation, consisting of nodes and edges, may not be able to reveal
the most compelling network differences when the reconstructed networks are dense
and homogeneous. In this paper, we leveraged the block information on the Region
Of Interest (ROI) based brain networks and studied the problem of blockwise brain
network visual comparison. An integrated visual analytics framework was proposed.
In the first stage, a two-level ROI block hierarchy was detected by optimizing
the anatomical structure and the predictive comparison performance
simultaneously. In the second stage, the NodeTrix representation was adopted and
customized to visualize the brain network with block information. We conducted
controlled user experiments and case studies to evaluate our proposed solution.
Results indicated that our visual analytics method outperformed the commonly used
node-link graph and adjacency matrix design in the blockwise network comparison
tasks. We have shown compelling findings from two real-world brain network data
sets, which are consistent with the prior connectomics studies.
PMID- 27514060
TI - Commanding a Brain-Controlled Wheelchair Using Steady-State Somatosensory Evoked
Potentials.
AB - In this work, we propose a novel brain-controlled wheelchair, one of the major
applications of brain-machine interfaces (BMIs), that allows an individual with
mobility impairments to perform daily living activities independently.
Specifically, we propose to use a steady-state somatosensory evoked potential
(SSSEP) paradigm, which elicits brain responses to tactile stimulation of
specific frequencies, for a user's intention to control a wheelchair. In our
system, a user had three possible commands by concentrating on one of three
vibration stimuli, which were attached to the left-hand, right-hand, and right
foot, to selectively control the wheelchair. The three stimuli were associated
with three wheelchair commands: turn-left, turn-right, and move-forward. From a
machine learning perspective, we also devise a novel feature representation by
combining spatial and spectral characteristics of brain signals. In order to
validate the effectiveness of the proposed SSSEP-based system, we considered two
different tasks: 1) a simple obstacle-avoidance task within a limited time and;
2) a driving task along the predefined trajectory of about 40 m length, where
there were a narrow pathway, a door, and obstacles. In both experiments, we
recruited 12 subjects and compared the average time of motor imagery (MI) and
SSSEP-based controls to complete the task. With the SSSEP-based control, all
subjects successfully completed the task without making any collision while four
subjects failed it with MI-based control. It is also noteworthy that in terms of
the average time to complete the task, the SSSEP-based control outperformed the
MI-based control. In the other more challenging task, all subjects successfully
reached the target location.
PMID- 27514062
TI - Linear Channel Modeling and Error Analysis for Intra/Inter-Cellular Ca2+
Molecular Communication.
AB - The use of intra/inter-cellular calcium ion (Ca2+) signaling for molecular
communication (MC) is investigated in this paper. In particular, the elevation of
the intracellular Ca2+ concentration upon the external excitation, i.e., Ca2+
wave generation, and the intercellular propagation of Ca2+ wave over consecutive
cells are studied for information transmission. The main objective of this paper
is to develop a linear channel model for intra/inter-cellular Ca2+ MC. In this
context, the end-to-end Ca2+ MC system is studied under three blocks: the wave
generation, the gap junctional (intercellular) propagation, and the intracellular
propagation. The wave generation block captures the intracellular Ca2+ signaling
pathway including the release of Ca2+ from the organelles and the buffers inside
a cell, and the intake from the extracellular space. The gap junctional
(intercellular) propagation block captures the Ca2+ transition through the gap
junctions between the touching cells. The intracellular propagation block defines
the effect of the cytoplasmic diffusion. Using the developed blocks for the
different biophysical phenomena, the end-to-end channel gain and delay formulas
are derived. Furthermore, the bit error probability is studied to reveal the
impact of the detection threshold. This work provides the basis for the modeling,
analysis and the design of Ca2+ MC systems.
PMID- 27514063
TI - ML-Space: Hybrid Spatial Gillespie and Particle Simulation of Multi-Level Rule
Based Models in Cell Biology.
AB - Spatio-temporal dynamics of cellular processes can be simulated at different
levels of detail, from (deterministic) partial differential equations via the
spatial Stochastic Simulation algorithm to tracking Brownian trajectories of
individual particles. We present a spatial simulation approach for multi-level
rule-based models, which includes dynamically hierarchically nested cellular
compartments and entities. Our approach ML-Space combines discrete compartmental
dynamics, stochastic spatial approaches in discrete space, and particles moving
in continuous space. The rule-based specification language of ML-Space supports
concise and compact descriptions of models and to adapt the spatial resolution of
models easily.
PMID- 27514065
TI - A 30 $?mu?text{W}$ Remotely Powered Local Temperature Monitoring Implantable
System.
AB - An implantable local temperature monitoring system for a laboratory mouse is
presented. Magnetic coupling is used to remotely power the passive implant. The
temperatures of two local points are monitored by thermistors. A low-power
readout circuit is implemented by directly amplifying and resolving the sensor
response in the time domain. A free-running oscillator operating at 868 MHz
transmits the sensor data to the base station. The average power dissipation of
the implant is decreased by time interleaving between the sensor readout and the
data communication. The power transfer to the implant is also time interleaved
with other operations to avoid interference with data communication. A voltage
regulation loop for the implant based on controlling the duration of powering the
base station power amplifier is also described. A prototype chip is implemented
in 0.18 [Formula: see text] CMOS. The implant requires average RF power of 29.5
[Formula: see text] for operation and is capable of measuring two thermistors
with accuracy of +/-0.05 degrees C.
PMID- 27514066
TI - Tactile Apparent Motion on the Torso Modulates Perceived Forward Self-Motion
Velocity.
AB - The present study investigated whether a tactile flow created by a matrix of
vibrators in a seat pan simultaneously presented with an optical flow in
peripheral vision enhances the perceived forward velocity of self-motion. A brief
tactile motion stimulus consisted of four successive rows of vibration, and the
interstimulus onset between the tactile rows was varied to change the velocity of
the tactile motion. The results show that the forward velocity of self-motion is
significantly overestimated for rapid tactile flows and underestimated for slow
ones, compared with optical flow alone or non-motion vibrotactile stimulation
conditions. In addition, the effect with a temporal tactile rhythm without
changing the stimulus location was smaller than that with spatiotemporal tactile
motion, with the interstimulus onset interval to elicit a clear sensation of
tactile apparent motion. These findings suggest that spatiotemporal tactile
motion is effective in inducing a change in the perceived forward velocity of
self-motion.
PMID- 27514067
TI - Randomized Prediction Games for Adversarial Machine Learning.
AB - In spam and malware detection, attackers exploit randomization to obfuscate
malicious data and increase their chances of evading detection at test time,
e.g., malware code is typically obfuscated using random strings or byte sequences
to hide known exploits. Interestingly, randomization has also been proposed to
improve security of learning algorithms against evasion attacks, as it results in
hiding information about the classifier to the attacker. Recent work has proposed
game-theoretical formulations to learn secure classifiers, by simulating
different evasion attacks and modifying the classification function accordingly.
However, both the classification function and the simulated data manipulations
have been modeled in a deterministic manner, without accounting for any form of
randomization. In this paper, we overcome this limitation by proposing a
randomized prediction game, namely, a noncooperative game-theoretic formulation
in which the classifier and the attacker make randomized strategy selections
according to some probability distribution defined over the respective strategy
set. We show that our approach allows one to improve the tradeoff between attack
detection and false alarms with respect to the state-of-the-art secure
classifiers, even against attacks that are different from those hypothesized
during design, on application examples including handwritten digit recognition,
spam, and malware detection.In spam and malware detection, attackers exploit
randomization to obfuscate malicious data and increase their chances of evading
detection at test time, e.g., malware code is typically obfuscated using random
strings or byte sequences to hide known exploits. Interestingly, randomization
has also been proposed to improve security of learning algorithms against evasion
attacks, as it results in hiding information about the classifier to the
attacker. Recent work has proposed game-theoretical formulations to learn secure
classifiers, by simulating different evasion attacks and modifying the
classification function accordingly. However, both the classification function
and the simulated data manipulations have been modeled in a deterministic manner,
without accounting for any form of randomization. In this paper, we overcome this
limitation by proposing a randomized prediction game, namely, a noncooperative
game-theoretic formulation in which the classifier and the attacker make
randomized strategy selections according to some probability distribution defined
over the respective strategy set. We show that our approach allows one to improve
the tradeoff between attack detection and false alarms with respect to the state
of-the-art secure classifiers, even against attacks that are different from those
hypothesized during design, on application examples including handwritten digit
recognition, spam, and malware detection.
PMID- 27514068
TI - Multiparametric Non-Negative Matrix Factorization for Longitudinal Variations
Detection in White-Matter Fiber Bundles.
AB - Processing of longitudinal diffusion tensor imaging (DTI) data is a crucial
challenge to better understand pathological mechanisms of complex brain diseases
such as multiple sclerosis (MS) where white-matter (WM) fiber bundles are
variably altered by inflammatory events. In this study, we propose a new fully
automated method to detect longitudinal changes in diffusivity metrics along WM
fiber bundles. The proposed method is divided in three main parts: 1)
preprocessing of longitudinal diffusion acquisitions, 2) WM fiber-bundle
extraction, and 3) application of nonnegative matrix factorization and density
based local outliers algorithms to detect and delineate longitudinal variations
appearing in the cross section of the WM fiber bundle. In order to validate our
method, we introduce a new model to simulate real longitudinal changes based on a
generalized Gaussian probability density function. Moreover, we applied our
method on longitudinal data. High level of performances were obtained for the
detection of small longitudinal changes along the WM fiber bundles in MS
patients.
PMID- 27514069
TI - A Scalable Approach to Capacitated Arc Routing Problems Based on Hierarchical
Decomposition.
AB - The capacitated arc routing problem (CARP) is a challenging optimization problem
with lots of applications in the real world. Numerous approaches have been
proposed to tackle this problem. Most of these methods, albeit showing good
performance on CARP instances of small and median sizes, do not scale well to
large-scale CARPs, e.g., taking at least a few hours to achieve a satisfactory
solution on a CARP instance with thousands of tasks. In this paper, an efficient
and scalable approach is proposed for CARPs. The key idea of the proposed
approach is to hierarchically decompose the tasks involved in a CARP instance
into subgroups and solve the induced subproblems recursively. The output of the
subproblems at the lower layer in the hierarchy is treated as virtual tasks and
new subproblems are formulated based on these virtual tasks using clustering
techniques. By this means, the number of tasks (or virtual tasks) decreases
rapidly from the bottom to the top layers of the hierarchy, and the sizes of all
subproblems at each layer can be kept tractable even for very large-scale CARPs.
Empirical studies are conducted on CARP instances with up to 3584 tasks, which
are an order of magnitude larger than the number of tasks involved in all CARP
instances investigated in the literature. The results show that the proposed
approach significantly outperforms existing methods in terms of scalability.
Since the proposed hierarchical decomposition scheme is designed to obtain a good
permutation of tasks in a CARP instance, it may also be generalized to other hard
optimization problems that can be formulated as permutation-based optimization
problems.
PMID- 27514071
TI - Cooperative Exploration and Networking While Preserving Collision Avoidance.
AB - Monitoring of large complex environments, such as underwater environments, is an
important task in surveillance. An information (sensor) network can be built to
achieve the task. To build an information network in an unknown workspace, we use
multiple robots deploying information nodes. While robots build the network, they
localize themselves as well as deployed nodes in the global coordinate system.
Our multirobot networking strategy is as follows: each robot iteratively visits a
frontier, which borders an unsensed area, until all areas are explored. As
multiple robots explore the workspace, a robot must avoid colliding with another
robot as well as with an obstacle. Hence, we introduce collision avoidance
control laws and integrate the control laws with our cooperative networking
strategy. Using MATLAB simulations, we verify the scalability and effectiveness
of both our networking strategy and the collision avoidance control laws.
PMID- 27514072
TI - Influence of sizes of abutments and fixation screws on dental implant system: a
non-linear finite element analysis.
AB - The purpose of this study is to discuss the influence of sizes of abutments and
fixation screws on immediately loaded dental implants in mandibular bones using
nonlinear finite element methods. Abutments with three unilateral wall
thicknesses and fixation screws with three diameters are analyzed to compare the
stresses and deformations under a vertical or oblique force of 130 N. The
nonlinearity due to friction contacts between the fixation screw, the abutment,
the implant, and the bone is taken into account. The results showed that improper
sizes of abutments and fixation screws would increase the stress and deformation
of the dental implant system. If possible, the diameter of fixation screw should
not be smaller than Phi1.0 mm, the diameter between Phi1.0 mm and Phi1.2 mm is
acceptable. The fixation screw diameter preferably exceeds Phi1.4 mm. The
unilateral wall thickness >0.5 mm is optimal selection for abutments.
PMID- 27514073
TI - Holoentropy enabled-decision tree for automatic classification of diabetic
retinopathy using retinal fundus images.
AB - Diabetic retinopathy (DR) is the most common diabetic eye disease. Doctors are
using various test methods to detect DR. But, the availability of test methods
and requirements of domain experts pose a new challenge in the automatic
detection of DR. In order to fulfill this objective, a variety of algorithms has
been developed in the literature. In this paper, we propose a system consisting
of a novel sparking process and a holoentropy-based decision tree for automatic
classification of DR images to further improve the effectiveness. The sparking
process algorithm is developed for automatic segmentation of blood vessels
through the estimation of optimal threshold. The holoentropy enabled decision
tree is newly developed for automatic classification of retinal images into
normal or abnormal using hybrid features which preserve the disease-level
patterns even more than the signal level of the feature. The effectiveness of the
proposed system is analyzed using standard fundus image databases DIARETDB0 and
DIARETDB1 for sensitivity, specificity and accuracy. The proposed system yields
sensitivity, specificity and accuracy values of 96.72%, 97.01% and 96.45%,
respectively. The experimental result reveals that the proposed technique
outperforms the existing algorithms.
PMID- 27514074
TI - Congenital diaphragmatic hernia: endotracheal fluid phospholipidic profile
following tracheal occlusion in an experimental model.
AB - OBJECTIVE: To compare endotracheal fluid (EF) and amniotic fluid (AF)
phospholipidic profile changes following tracheal occlusion (TO) in the
congenital diaphragmatic hernia (CDH) fetal lamb model, in order to support the
efficacy of TO on lung maturity. METHODS: A diaphragmatic defect was induced at
70 days' gestation, TO was carried out at day 102 and cesarean section at 136
days' gestation. EF and AF samples, collected at delivery, were evaluated using
mass spectrometry (the analysis focused on palmitoyloleoyl-phosphatidylcholine
[POPC, PC(18:1/16:0)], dipalmitoyl-phosphatidylcholine [DPPC, PC(16:0/16:0)] and
sphingomyelins [SMs]). RESULTS: The effects of CDH and TO were different on AF
and EF. POPC levels were higher than DPPC levels in AF of healthy lambs.
Following induction of the diaphragmatic malformation, an evident decrease in
POPC was noted, while a substantial return to normal POPC levels and an increased
DPPC peak were prompted by the TO. After CDH induction, a decrease in N-palmitoyl
D-sphingomyelin [SM(d18:1/16:0)] was revealed (P<0.01) and an increased peak in
SMs in AF was prompted by the TO (P=0.05). While the most represented
phosphatidylcholine (PC) species in EF of healthy lambs was DPPC, CDH induced a
decrease in the DPPC peak and treatment with TO induced its partial recovery. SMs
were detectable only in healthy EF samples. CONCLUSION: The phospholipid recovery
profile following TO suggests the potential role of this therapy in restoring
processes involved in surfactant-mediated lung maturation, even though other
interactions involved in AF turnover should be considered. Moreover, these
metabolites could be used as biomarkers of fetal pulmonary development.
PMID- 27514075
TI - Biomarkers of spontaneous preterm birth: a systematic review of studies using
multiplex analysis.
AB - OBJECTIVE: Despite decades of research on risk indicators of spontaneous preterm
birth (PTB), reliable biomarkers are still not available to screen or diagnose
high-risk pregnancies. Several biomarkers in maternal and fetal compartments have
been mechanistically linked to PTB, but none of them are reliable predictors of
pregnancy outcome. This systematic review was conducted to synthesize the
knowledge on PTB biomarkers identified using multiplex analysis. MATERIALS AND
METHODS: Three electronic databases (PubMed, EMBASE and Web of Science) were
searched for studies in any language reporting the use of multiplex assays for
maternal biomarkers associated with PTB published from January 2005 to March
2014. RESULTS: Retrieved citations (3631) were screened, and relevant studies
(33) were selected for full-text reading. Ten studies were included in the
review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three
studies) followed by MIP-1beta, GM-CSF, Eotaxin, and TNF-RI (two studies) were
reported more than once in maternal serum. However, results could not be combined
due to heterogeneity in type of sample, study population, assay, and analysis
methods. CONCLUSION: By this systematic review, we conclude that multiplex assays
are a potential technological advancement for identifying biomarkers of PTB,
although no single or combination of biomarkers could be identified to predict
PTB risk.
PMID- 27514076
TI - Glutathione and glutathione derivatives in immunotherapy.
AB - Reduced glutathione (GSH) is the most prevalent non-protein thiol in animal
cells. Its de novo and salvage synthesis serves to maintain a reduced cellular
environment, which is important for several cellular functions. Altered
intracellular GSH levels are observed in a wide range of pathologies, including
several viral infections, as well as in aging, all of which are also
characterized by an unbalanced Th1/Th2 immune response. A central role in
influencing the immune response has been ascribed to GSH. Specifically, GSH
depletion in antigen-presenting cells (APCs) correlates with altered antigen
processing and reduced secretion of Th1 cytokines. Conversely, an increase in
intracellular GSH content stimulates IL-12 and/or IL-27, which in turn induces
differentiation of naive CD4+ T cells to Th1 cells. In addition, GSH has been
shown to inhibit the replication/survival of several pathogens, i.e. viruses and
bacteria. Hence, molecules able to increase GSH levels have been proposed as new
tools to more effectively hinder different pathogens by acting as both
immunomodulators and antimicrobials. Herein, the new role of GSH and its
derivatives as immunotherapeutics will be discussed.
PMID- 27514078
TI - Phenylboronic acid-decorated gelatin nanoparticles for enhanced tumor targeting
and penetration.
AB - Phenylboronic acid-decorated nanoparticles (NPs) were prepared for tumor-targeted
drug delivery. 3-carboxyphenylboronic acid (3-CPBA) was modified on the surface
of conventional gelatin NPs (designated as NP1) to give tumor-targeting NPs
(designated as NP2). The morphology and stability of NP1 and NP2 were then
investigated using transmission electron microscopy, scanning electron
microscopy, and dynamic light scattering. The results show that both NP1 and NP2
are spherical-like and kinetically stable under various conditions. Doxorubicin
hydrochloride (DOX) was used as a model anticancer drug and was loaded into NP1
(NP1-DOX) and NP2 (NP2-DOX). The i n vitro cellular uptake and cytotoxicity of
NP1-DOX and NP2-DOX were measured using SH-SY5Y cells, H22 cells, and HepG2
cells. Tumor penetration, accumulation, and antitumor activity were investigated
using SH-SY5Y tumor-like spheroids and H22 tumor-bearing mice. All results
demonstrated that the conjugation of 3-CPBA can efficiently enhance non-targeted
NPs' tumor-homing activity, thus improving their tumor accumulation and antitumor
effect.
PMID- 27514079
TI - Rapid laser sintering of metal nano-particles inks.
AB - Fast sintering is of importance in additive metallization processes and
especially on sensitive substrates. This work explores the mechanisms which set
limits to the laser sintering rate of metal nano-particle inks. A comparison of
sintering behavior of three different ink compositions with laser exposure times
from micro-seconds to seconds reveals the dominant factor to be the organic
content (OC) in the ink. With a low OC silver ink, of 2% only, sintering time
falls below 100 MUs with resistivity <*4 bulk silver. Still shorter exposure
times result in line delamination and deformation with a similar outcome when the
OC is increased.
PMID- 27514080
TI - Mesoporous InN/In2O3 heterojunction with improved sensitivity and selectivity for
room temperature NO2 gas sensing.
AB - Establishing heterostructures is a good strategy to improve gas sensing
performance, and has been studied extensively. In this work, mesoporous InN/In2O3
composite (InNOCs) heterostructures were prepared through a simple two-step
strategy involving hydrothermal synthesis of In2O3 and subsequent nitriding into
InN-composite In2O3 heterostructures. We found that the InN content has great
influence on the resistance of InNOCs, and thus, the gas sensing performance. In
particular, InNOC-36.9 (with InN content of 36.9% in the composites) shows an
excellent sensing response towards different concentrations of NO2, as well as
good stability after one week of exposure to 200 ppb NO2 at room temperature. The
highest sensing response (DeltaR/R0 ) is up to 1.8 for the low NO2 concentration
of 5 ppb. Even more significantly, the theoretical limit of detection (LOD) of
the InNOC-36.9 sensor is 31.7 ppt based on a signal-to-noise ratio of 3 (the
measured LOD is 5 ppb), which is far below the US NAAQS value (NO2: 53 ppb). In
addition, a rational band structure model combined with a surface reaction model
is proposed to explain the sensing mechanism.
PMID- 27514077
TI - Scavengers of reactive gamma-ketoaldehydes extend Caenorhabditis elegans lifespan
and healthspan through protein-level interactions with SIR-2.1 and ETS-7.
AB - Isoketals (IsoKs) are highly reactive gamma-ketoaldehyde products of lipid
peroxidation that covalently adduct lysine side chains in proteins, impairing
their function. Using C. elegans as a model organism, we sought to test the
hypothesis that IsoKs contribute to molecular aging through adduction and
inactivation of specific protein targets, and that this process can be abrogated
using salicylamine (SA), a selective IsoK scavenger. Treatment with SA extends
adult nematode longevity by nearly 56% and prevents multiple deleterious age
related biochemical and functional changes. Testing of a variety of molecular
targets for SA's action revealed the sirtuin SIR-2.1 as the leading candidate.
When SA was administered to a SIR-2.1 knockout strain, the effects on lifespan
and healthspan extension were abolished. The SIR-2.1-dependent effects of SA were
not mediated by large changes in gene expression programs or by significant
changes in mitochondrial function. However, expression array analysis did show SA
dependent regulation of the transcription factor ets-7 and associated genes. In
ets-7 knockout worms, SA's longevity effects were abolished, similar to sir-2.1
knockouts. However, SA dose-dependently increases ets-7 mRNA levels in non
functional SIR-2.1 mutant, suggesting that both are necessary for SA's complete
lifespan and healthspan extension.
PMID- 27514081
TI - [PECULIARITIES OF COURSE OF TRAUMATIC DISEASE IN THE INJURED PERSONS IN COMBINED
CRANIOABDOMINAL TRAUMA].
AB - Prospective investigation of the traumatic disease course was conducted in 71
injured persons, suffering a combined cranioabdominal trauma with the objective
to determine the main functional systems and dynamics of their state severity.
The occurrence rate and the severity degree of cardiovascular insufficiency were
determined--in accordance to indices of the integrative body rheography and
integrative dual frequency impedansometry, respiratory insufficiency (PaO2/FiO2
ratio), the organ insufficiency severity (in accordance to SOFA scale). There was
established, that changes in respiratory and cardiovascular systems are
corresponding to the staged pathogenetic characteristics of the traumatic disease
periods. So on, it is expedient to perform the urgent and postponed operative
interventions in a period of their relative stabilization. The presence of severe
craniocerebral trauma, as a part of a combined cranioabdominal trauma causes
significant and durable impairment of the functional systems activity.
PMID- 27514082
TI - [BACTERIOLOGICAL ASPECTS OF AN ACUTE APPENDICITIS].
AB - Peculiarities of microflora in the appendix mucosa and abdominal exudate in
different morphological forms of an acute appendicitis (AA) were studied up. In
accordance to the bacteriological investigations data, anaerobic, and aerobic
microorganisms in AA were revealed in a monoculture and in association, more
frequently--obligate anaer- obes (bacteroids) with E. coli--in 82 (80.39%)
observations, staphylococcus--in 52 (50.98%), fecal streptococcus--in 19
(18.63%). With progression of inflammatory process and destructive changes in the
appendix wall the quantity of bacteroids and enterobacteria have had enhanced,
while the quantity of lacto- and bifidumflora-- reduced.
PMID- 27514083
TI - [SUBTOTAL COLECTOMY WITH MESORECTUMECTOMY IN SURGICAL TREATMENT OF A
HIRSCHSPRUNG'S DISEASE IN ADULTS].
AB - Hirschsprung's disease (HD) in adults constitutes a rare cause of chronic
constipation. Surgical intervention constitutes the only one radical method of
treatment of HD. The investigation objective was to improve the functional
results of treatment of HD in adults, using a new surgical approach elaboration.
The method of surgical treatment of a HD in adults was proposed, which envisages
a conduction of distal subtotal colecto- my and total mesorectumectomy with
formation of a coecoreservoiroanal anastomosis. Application of the method
proposed have had promoted an essential reduction of unfair functional results in
a remote postoperative period.
PMID- 27514084
TI - [SURGICAL TREATMENT OF COMPLICATED GASTRODUODENAL ULCER].
AB - Results of operative treatment of 437 patients with complicated gastroduodenal
ulcer were summarized. The modern views on the problem of conservative therapy
for gas- troduodenal ulcer were presented. A rational individual approach with a
certain terms is necessary for conservative treatment of gastroduodenal ulcer. A
real way for improve- ment of the patients treatment results--it is a combination
of effective conservative treatment with a timely established indications for a
planned operative treatment before dangerous complications occur.
PMID- 27514085
TI - [SYSTEMIC CYTOKINOTHERAPY, USING BETALEUKIN IN A COMPLEX TREATMENT OF AN ACUTE
GASTRODUODENAL ULCER BLEEDING].
AB - Results of surgical treatment for an acute ulcer gastroduodenal bleeding in 120
patients, ageing 16-75 yrs old, were analyzed. In 20 of them a gastric ulcer was
a cause of bleeding, while in 84--a duodenal ulcer, and in 16--a coexistent
gastroduodenal ulcer. The bleeding activity was estimated in accordance to J.
Forrest classification. In 57 patients (a comparison group) preoperatively and
postoperatively a complex of a standard basal conservative therapy without
immunocorrection was conducted, and in 63 (the main group)--a systemic
cytokinotherapy (SCKTH), using betaleukin, was applied postoperatively
additionally in a complex of therapy. A content of CD3+, CD4+, CD8+, CD19+, IgA,
IgM, IgG was estimated in dynamics, as well as circulating immune complexes,
phagocytic index, phagocytic number. There was established, that a dysbalance
depth in the immune status have had depended upon the blood loss severity. The
SCKTH application is pathogenetically substantiated, it promotes the immune
status normalization, as well as a more favorable course of postoperative period
and the results of treatment improvement.
PMID- 27514086
TI - [PROPHYLAXIS OF COMPLICATIONS OF LAPAROSCOPIC CHOLECYSTECTOMY IN PATIENTS WITH
THE ISCHEMIC HEART DISEASE].
AB - Results of examination and surgical tratment of 56 patients, suffering chronic
calculous cholecystitis with concomitant schemic heart disease, were analyzed. In
all the patients a laparoscopic cholecystectomy was performed. Monitoring of
cardiovascular compli- cations was estimated with the help of a Helter recording
of EGG intraoperatively and in the early postoperative period. Depending on a
kind of preoperative preparation done, the patients were divided on two groups:
those, to whom cardioprotection using a Vasopro preparation was conducted, and
those without cardioprotection. Depending on the intraoperative pneumoperitoneum
regime used in every group two subgroups were delineated: in intraabdominal
pressure 5-7.9 mm Hg and 8-10 mm Hg. In the patients, to whom cardioprotection
was conducted and operative intervention in a carboxyperitoneum regime performed
while intraabdominal pressure 5-7.9 mm Hg, a frequency of cardiovascular
complications was lesser than in a control group.
PMID- 27514087
TI - [FACTORIAL ANALYSIS IN PROGNOSTICATION OF INFECTIOUS COMPLICATIONS AFTER
SIMULTANT OPERATIVE INTERVENTIONS FOR BILIARY CALCULOUS DISEASE].
AB - Prognostication of postoperative complications, having a certain high risk of
occurrence in surgical treatment of biliary calculous disease, using laparoscopic
and open access, peculiarly while performing simultant operative interventions,
may promote the treatment efficacy rising in such patients. A multifactorial
disperse analysis, using Statistica 6 for Windows (StatSoft), was applied for
prognostication of risk for the infectious complications occurrence while a
simultant operative interventions conduction for biliary calculous disease. The
indices, which, in accordance to the pathophysiological processes character, may
influence the postoperative complications occurrence rate, were analyzed. During
conduction of this procedure, a great quantity of the parameters, which were
determined in the patients, were transformed to a lesser quantity of independent
causes. In the one cause a several variables were cojoined, which, as a rule,
correlate with each other closely. On a subsequent stage a sum of the points of
the prognosis causes for the risk of the postoperative purulent complications
occurrence, as the points sum for the status severity and the operative
intervention severity, were calculated. A prognostical validity of the algorithm
proposed was tested in clinical conditions, its significance was estimated.
PMID- 27514088
TI - [A FITZ-HUGH-CURTIS SYNDROME AS A PREMISE OF THE INFLAMMATORY DISEASES OF A
HEPATOPANCREATOBILIARY ZONE ORGANS].
AB - A content of a biliary ways microflora and its correlation with clinical form and
severity of inflammatory-destructive processes in hepatopancreatobiliary zone
were studied up. The investigation objective was the optimization of a treatment-
diagnostic tactics for the complications and remote recurrences rate reduction in
a complicated biliary calculous disease. There was established, that a standard
bacteriological investigation do not give a possibility to estimate some causes
of a biliary ducts affection, a chlamidial infection in particular. So on, for
the individual antibacterial therapy choosing a more detailed and modern
examination of patients is needed.
PMID- 27514089
TI - [MORPHOLOGICAL CRITERIA OF THE ENTERAL INSUFFICIENCE SEVERITY IN A DIFFUSE
PERITONITIS FOR DETERMINATION OF A SUBSEQUENT TACTICS OF THE PATIENTS TREATMENT].
AB - The results of treatment of 87 patients for diffuse peritonitis (DP) were
analyzed, in whom the enteral insufficiency (El) was estimated. The small
intestine biopsies for morphological investigations were taken during its
resection performance on the border between the pathologically changed and intact
wall. Comparative morphometric analysis of destructive and inflammatory processes
in a small intestine was conducted for establishment of morphological criteria
for the EI prognosis in a DP. Morphological criteria of the EI severity were
established for determination of a subsequent tactics for the patients' treatment
and prognosis.
PMID- 27514090
TI - [THE ROLE OF COMPUTER TOMOGRAPHY WHILE CHOOSING THE ABDOMINOPLASTY METHOD].
AB - The role of computer tomography (CT), while choosing the abdominoplasty method in
the patients with different types of the anterior abdominal wall deformity
present. For CT date the anterior abdominal wall deformity type was determined in
the accordance to it--the operation volume needed. Depending on the changes
degree the patients were divided on 5 groups, and in accordance to the deformity
type present a necessary correction was made. The CT application have had
permitted to determine the changes degree in the anterior abdominal wall, and to
choose a necessary volume of abdominoplasty precisely.
PMID- 27514091
TI - [PROPHYLAXIS OF POSTOPERATIVE HYPERALGESIA, BASED ON MORPHOLOGICAL SUBSTANTIATION
OF THE ANALGESIA METHOD].
AB - The investigation was conducted in 20 children, operated on for abdominal
oncological diseases in a 2010-2015 yrs period, using various methods of
analgesia. While application of a constant infusion of high doses of phentanyl--1
4 MKr/(kg x h) in perioperative period the occurrence of the opiate-induced
hyperalgesia is possible with the accompanied morphological changes in intestinal
wall; in anesthesia of a transverse abdominal muscle (a TAP-blockade) and
combined spinal epidural analgesia such changes were not observed.
PMID- 27514092
TI - [EFFICACY OF RADIOFREQUENCY ABLATION OF AORTORENAL SYMPATHETIC NODES IN PATIENTS
IN ARTERIAL HYPERTENSION].
AB - Efficacy of radiofrequency ablation (RFA) of prevertebral sympathetic nodes,
concern- ing the arterial pressure lowering in 36 patients, suffering hypertonic
disease and coex- istent heart diseases, was analyzed. In 12 mo after RFA a
systolic arterial pressure lowering at average throughout the group by (3.24 +/-
1.15) kPa, or (24.3 +/- 8.6) mm Hg, diastolic arterial pressure--by (1.51 +/-
0.45) kPa, or (11.3 +/- 3.4) mm Hg was noted. RFA of prevertebral sympathetic
nodes have had promoted a stable lowering of arterial pressure in patients,
suffering chronic hypersympathicotony.
PMID- 27514093
TI - [THE COMPARATIVE ANALYSIS RESULTS OF ENDOVASCULAR LASER COAGULATION AND A
STANDARD PHLEBECTOMY IN THE TREATMENT OF CHRONIC DISEASES OF THE LOWER
EXTREMITIES VEINS].
AB - The results of treatment of 58 patients, suffering chronic diseases of the lower
extremities veins, were analyzed. In 28 patients a vertical reflux was eliminated
using endovascular laser coagulation, in 32 patients--a standard phlebectomy in
accordance to Babcock method was performed. The complications rate was compared
as well as the term of the patients' stationary treatment. After elimination of
endovascular laser coag- ulation the complications rate and severity is
significantly lesser, than after a standard phiebectomy. In accordance to the
ultrasonographic duplex scanning data in 12 mo in one patient a partial
recanalization of large subcutaneous vein was noted. A total fibrous
transformation of the coagulated venous trunks was achieved in 95.24% of the
patients. Duration of postoperative stationary treatment have had reduced from
(4.8 +/- 0.8) to (1.2 +/- 0.1) days (p < 0.001).
PMID- 27514094
TI - [POSSIBILITIES OF MODERN TECHNOLOGIES IN THE TREATMENT OF PLEURAL EMPYEMA].
AB - The data, concerning videothoracoscopic operations application in the acute
pleural empyema treatment in 462 patients, were adduced. Efficacy of
videothoracoscopic operations, using electrowelding and radiofrequency surgical
complexes with possibility to eliminate pulmonary-pleural fistulas, was shown.
Positive clinical effect was noted in 443 (95.9%) patients, duration of
stationary treatment have constituted 11.1 days at average. The complications
have had occurred in 19 (4.1%) patients. All the patients are alive.
PMID- 27514095
TI - [MODERN APPROACHES TO TREATMENT OF A DONOR'S WOUNDS IN THE INJURED PERSONS WITH
THE BURNS].
AB - The impact of the treatment method proposed, using antioxidant therapy in
patients, suffering the burns, on the speed and efficacy of the donor's wounds
healing in their extremities was studied. In a control group of patients a
standard treatment of the donor's wounds in extremities was conducted, while in
the main group of patients the treatment was added with lymphotropic injection of
antioxidant preparation Mexidol. Due to application of the method proposed, the
wounds healing in the main group of the injured persons have had occurred
significantly faster, than in the patients of a control group, and the
complications of the wounds healing were absent.
PMID- 27514096
TI - [STUDYING OF MORPHOLOGICAL PECULIARITIES OF SUBMANDIBULAR SALIVARY GLANDS AFTER
GASTRIC RESECTION IN EXPERIMENT].
AB - The impact of gastric resection on the submandibular salivary gland (SSG) state,
using histological and histochemical methods of investigation in experiment, was
studied up. A relative mass of a SSG after gastric resection conduction have had
reduced, and the accompanying changes in stroma were revealed with the gland's
secretion enhancement. Essential dystrophic changes in the SSG parenchyma and
stroma after gastric resection conduction may cause a pronounced disorders of
their function.
PMID- 27514097
TI - [THE BONE DEFECT HEALING UNDER THE INFLUENCE OF RADIAL EXTRACORPOREAL SHOCK-WAVE
THERAPY IN EXPERIMENT].
AB - In experiment on 24 rabbits the processes of reparative osteogenesis in
perforated defect of proximal tibial metaphysis under the influence of
extracorporeal shock-wave therapy were studied. In accordance to data of
clinical, roentgenological and morphological investiagations, conducted in terms
5, 15, 30 and 45 days of observation, there was established, that under the
influence of extracorporeal shock-wave therapy in the bone marrow in the
traumatic region a vasodilatation, as well as the blood cells exit from
capillaries and sinusoid vessels with creation of massive regions of osseous
endostal regenerate, guaranteeing the tibial integrity restoration, occurs.
PMID- 27514098
TI - [METABOLIC CHANGES OF SKELETAL MUSCLES IN TRAUMATIC INJURY OF PERIPHERAL NERVE
AND AUTOPLASTY IN EXPERIMENT].
AB - The changes in metabolism of the amine acids, enzymes, electrolytes, fat acids
(FA) in skeletal muscles of anterior and posterior extremities of rats in
significant defects of peripheral nerve and its autoplasty were studied in
experimental investigation. Metabolic changes in skeletal muscles are accompanied
by significant intensity of proteolysis, lowering of the enzymes activity,
energetic metabolism and in a less extent of the electrolytes balance and the FA
metabolism. After autoplasty of big defects in the traumatized nerve the
proteins' synthesis and restoration of activity of lactate dehydrogenase and
creatine phosphokinase constitute the markers of muscular tissue restoration.
Surgical restoration of the nerve is accompanied by a protein synthesis
activation in muscles, but normalization of the enzyme systems indices, the
lipids metabolism and the electrolytes balance was not observed. Metabolic
dysbalance needs a certain pharmacological correction and prevention of a
progress of pathological process in skeletal muscles.
PMID- 27514099
TI - [THE WAYS OF IMPROVEMENT OF A GASTRIC CANCER SURGICAL TREATMENT].
PMID- 27514100
TI - [PERFORATION OF PEPTIC ULCER: NONSTANDARD SITUATIONS AND NONSTANDARD DECISIONS].
PMID- 27514101
TI - [MALROTATION BOWEL PATIENT IF STRANGULATED INGUINAL HERNIA].
PMID- 27514102
TI - [ENDOVASCULAR ARREST OF EROSIVE BLEEDING FROM THE TONGUE ARTERY].
PMID- 27514103
TI - [OBSERVATION OF A FEMORAL ARTERY EMBOLISM, CAUSED BY A BULLET].
PMID- 27514104
TI - Washington Brings Renewed Focus to Payment Models of the Future.
PMID- 27514105
TI - New Directions in CMS Bundling: 2016 Update.
PMID- 27514106
TI - Improving Patient Flow Utilizing a Collaborative Learning Model.
AB - This initiative utilized a collaborative learning approach to increase knowledge
and experience in process improvement and systems thinking while targeting
improved patient flow in seven radiology modalities. Teams showed improvements in
their project metrics and collectively streamlined the flow for 530 patients per
day by improving patient lead time, wait time, and first case on-time start
rates. In a post-project survey of 50 project team members, 82% stated they had
more effective solutions as a result of the process improvement methodology, 84%
stated they will be able to utilize the process improvement tools again in the
future, and 98% would recommend participating in another project to a colleague.
PMID- 27514107
TI - Lean Six Sigma and Employee Development.
PMID- 27514108
TI - Enhancing the Imaging Experience for Pediatric Patients.
AB - The University of Maryland Medical Center's goal was to improve the safety and
comfort of pediatric imaging by enhancing the experience for children. Two
pediatric radiologists and two child life specialists worked together to create a
training program to help guide radiology technologists on how to approach and
interact with children undergoing medical imaging. The results of surveys
administered to technologists and parents or caregivers helped refine the
strategy for both creating training sessions for technologists and reading
materials for children and their parents to optimally prepare for the procedures.
Training sessions included information on language choices, developmental
considerations, comfort techniques, patient- and family-centered care practices,
procedural support techniques, and coping styles. Through the implementation of
learning sessions and distraction resources for technologists, and the
development of preparation books, the imaging experience for pediatric patients
at UMMC has improved.
PMID- 27514109
TI - De-nied!
AB - It is important to remain current on the latest edit and modifier guidelines from
the AMA, CMS, and your contracted payors. Failure to use modifiers correctly can
result in under- or overpayments and can put a provider at risk of penalties.
Also, since payors vary in how they adjudicate claims with modifiers, it is
important to monitor payments for claims with modifiers to make certain you are
being paid correctly.
PMID- 27514110
TI - ICD-10: Intervertebral Disc Disease.
PMID- 27514111
TI - Business Intelligence in Hospital Management.
AB - Business intelligence (BI) is a worthwhile investment, and will play a
significant role in hospital management in the near future. Implementation of BI
is challenging and requires resources, skills, and a strategy, but enables
management to have easy access to relevant analysis of data and visualization of
important key performance indicators (KPI). Modern BI applications will help to
overcome shortages of common "hand-made" analysis, save time and money, and will
enable even managers to do "self-service" analysis and reporting.
PMID- 27514112
TI - Observations from a Healthcare User.
PMID- 27514113
TI - Responsibility Training.
PMID- 27514114
TI - [Metamorphosis of psychology between 1860 and 1989 and their reflections in the
Leipzig, Berlin and Halle academies].
AB - The study discusses the approach to psychology and psychological topics in three
scientific academies, the Saxon Society of Sciences, the Prussian Academy of
Sciences and the Leopoldina Academy of Sciences. Four different uses of the
academies emerge: academies as a scene of transdisciplinary exchange and
emergence of new ideas, as a location for the presentation of normal scientific
research, as an arena of proclamations in science policy, and as a reputation
generating scene for a new, arising science-based profession and its associated
scientific discipline.
PMID- 27514115
TI - [Medical anthropology in academies: on the criticism of natural science medicine
exemplified by Viktor von Weizsacker].
AB - Viktor von Weizsacker (1886-1957) founded his concept of medical anthropology as
a clinician educated in internal medicine and neurology. He tried to broaden
natural scientific medicine psychosomatically focussing on the "sick human". The
natural scientific approach would exclude subjectivity, and therefore he
propagated the "introduction of the subject' (Einfuhrung des Subjekts) into the
life sciences. His own sensory physiological experiments and Sigmund Freud's
psychoanalysis inspired him essentially since the 1920s. In his main work Der
Gestaltkreis (gestalt circle) published in 1940 he stressed the "entity of
perceiving and moving" (Einheit von Wahrnehmen und Bewegen) in regard to relevant
aspects of medicine. In 1932, Weizsacker became a member of the Heidelberg
Academy of Sciences, whose president he was from 1947 till 1949; 1942 he became a
member of the Leopoldina. Primarily his merits as a neurologist were highly
appreciated. His medical anthropology was not relevant for his election by the
two academies. Nevertheless, there was a certain repudiation against the
objectivistic and materialistic Weltanschauung within the scientific community.
So, Paracelsus and Goethe were highly estimated as natural philosophical guides
for own conceptions. This was especially evident for the circle around Wilhelm
Troll and Karl Lothar Wolf in Halle, both members of the Leopoldina, who were
fascinated by Goethe's concept of "Gestalt". Weizsacker's lecture on "Gestalt und
Zeit" in Halle in 1942 fitted in the concept of those natural scientists.
PMID- 27514116
TI - [History of anatomy - academy history. On the development of scientific academies
in the Third Reich exemplified by anatomy].
AB - Research on the history of National Socialism has for decades ignored the German
academies of sciences as well as the subject of anatomy. This was due to the
rather minor roles the societies played in the scientific policy of the Third
Reich and role anatomy played in medicine during this period of time. Recent
investigations in both subjects were able to show how worthwhile the dealing with
seemingly minor aspects of National Socialist policies is: Those aspects can
especially help to sharpen the historical judgment of scientific and political
actions. On the basis of recent archival research this article tries to present
and analyze the subject of anatomy and the academies of sciences regarding their
reciprocal relationship between 1933 and 1945. Besides the Leopoldina, the
Prussian and the Bavarian Academies of Sciences will be focused on: By the
examples of the anatomists represented in these societies it can be shown how
anatomy as well as the societies developed under National Socialism and which
general tendencies, entanglements and differences are relevant for the matter.
The insight in this relationship focuses on the one hand on the anatomists
represented in the societies. On the other hand it deals with the presence of
anatomical research in the society, their meetings and publications, and
especially with ideology and crimes reflected in this research.
PMID- 27514117
TI - [Association of the Berlin German Academy of Science and the German Leopoldina
Academy of Natural Scientists with the Nazi medical crimes of its members after
1945].
AB - The paper examines how two renowned academies based in East Germany handled the
Nazi medical crimes of its members after 1945. It should be noted that both
institutions were differently affected by these crimes. This applies both in
terms of number of incriminated members, which is a consequence of the different
membership structure of the two academies, as well as the extent of their
involvement. Despite being apparently the less affected of the two, the former
Prussian Academy of Sciences responded more radically to the Nazi past of its
members and removed those accounted guilty from the academy before it was
reopened by the Soviet military administration on 1 July 1946. The reasons for
this are to be found mainly in the exposed situation of the academy, which was in
the center of the Soviet occupying power. The Leopoldina did not make such
adjustments of the membership lists. The reasons for the moderate dealing with
the Nazi crimes of its members are primarily in the attitude of the leading
representatives of the Leopoldina in Halle after 1945, in the continuity of the
members, and thus the thought structures--regardless of the ruling political
systems--and in the particular status of the Leopoldina as an all-German academy
tolerated by the SED.
PMID- 27514118
TI - Floor Plans.
AB - More and more hospitals, design firms and others are recognizing the value that
nurses can bring to facility design.
PMID- 27514119
TI - DOING THEIR HOMEWORK.
AB - One health care network is proving the value of community health workers to reach
patients at home. The effort improves population health, identifies patients who
are at risk of illness and averts preventable hospitalizations.
PMID- 27514120
TI - The Most Vexing Problem in IT.
AB - The inability to share patient records from one physician to the next and one
hospital to the next is a huge roadblock in efforts to improve health care
delivery. Some hospitals are fed up, and they're taking the bull by the horns.
PMID- 27514121
TI - PAY CHECKS.
AB - Hospital boards are well-versed in overseeing executive compensation Now they're
being encouraged to take a greater role in physician compensation, too, to
improve strategic alignment and reduce risk.
PMID- 27514122
TI - When Words Matter.
AB - Too often, terminology used in a hospital is inconsistent and can hurt planning,
operations, communication and credibility. Hhere's how boards can encourage a
consistent lexicon.
PMID- 27514123
TI - Preserving a Legacy.
AB - When a nonprofit hospital is bought by a for-profit health care system, a central
concern for boards is preserving the charitable mission, values and legacy of
their organization.
PMID- 27514124
TI - Exploring Community Health Needs.
AB - The Health Research & Educational Trust has five recommendations to maximize the
effectiveness of a hospital's community health assessment.
PMID- 27514125
TI - [CHARACTERISTICS OF VAGINAL ECOSYSTEM IN ENDOCERVICITIS CHLAMYDIALIS].
AB - The study aims: 1. To analyze and study the specifics of microbiocenoses of
exocervix at endocervicitis chlamydialis, to differentiate the spectrum of
stimuli, and establish the leading role of Chl. trachomatis in the genesis of
this process. 2. To determine the leading role of the method of direct (bed-side)
microscopy for early and rapid diagnosis of cervicitis and conducting etiotropic
therapy. We determined the incidence of endocervicitis chlamydialis, with cause
Chl. trachomatis-45.1%, (319 DIF (+) patients out of 708 surveyed), p <0.05, in
the Rousse region. Studies indicator presence or absence of vaginal infection,
Trichomonas vaginalis, Gardnerella, Candida, Staphiloocus aureus, E. coli,
Proteus, Streptoccocus agalactae, the differences between the two samples in
terms of the variable was not statistically significant. In our study, in
patients with endocervicitis, the incidence of Trichom. vaginalis is 7.0%,
Gardnerella-24.4%, Candida-21.4%, Streptococcus agalactae-7.1%, Staphylococcus
aureus-6.3%, E. coli-0.4%, Proteus-0.2%. The frequency of Trichomonas vaginalis,
npu nauueHmku c endocervicitis chlamydialis e 3.2%, Gardnerella-10.8%, Candida
alb. -9.2%, Candida tropicans-0.2% Streptoccocus agalactae-3.3%, Staphyllococus
aureus-2.4%, E.coli-0.0%, Proteus-0.0%.The majority of patients with
endocervicitis chlamydialis, no other co-infection unless Chl. trachomatis.
PMID- 27514126
TI - [EARLY DETECTION OF PREECLAMPSIA].
AB - The preeclampsia is one of the most serious complications in the second half of
the pregnancy with a high risk of perinatal maternal and neonatal mortality. The
study is aiming to determine which pregnant women have a higher risk of
developing preeclampsia with a view to the subsequent antenatal care, on the base
of the individual factors. MATERIAL AND METODS: From prospectively followed
pacients is collected information by a questionnaire and sonographic examination
at 11-13 weeks of gestation/w.g./ + 6 days, at the point of biochemical screening
implementation. Selected is a group of women with one fetus pregnancy, non
smokers, without chromosomal and structural anomalies of the fetus, excluding
those taking prophylactic low-dose of aspirin. The Doppler examination was
transabdominaly performed on the ascending branch of the A. Uterina at the level
of OICC.Pusatility and resistance index /Pi and Ri/ are bilaterally evaluated and
converted to MoM for the relevant age of gestation. RESULTS: The information
about the taken values of Pi, Ri, the presence of diastolic incisures and the
development of preeclampsia /PE/ or pregnancy indused hypertension /PIH/ is
analyzed at 205 pregnant women. Out of them high values of Pi have 9 pregnant
women, who subsequently developed PE or PlH. CONCLUSIONS: The measurement of Pi
at 12-13 weeks of gestation and presence of diastolic incisures have prognostic
importance for the development of PE in the later period of pregnancy. The values
of Ri, taken at 12-13 weeks of gestation have not essential importance in the
forecast of preeclamsia development.
PMID- 27514127
TI - [PROGNOSTIC MODELS IN MODERN MANAGEMENT OF VULVAR CANCER].
AB - AIM: The aim of the research was to evaluate and analyse prognosis and prognostic
factors in patients with squamous cell vulvar carcinoma after primary surgery
with individual approach applied during the course of treatment. MATERIALS AND
METHODS: In the period between January 2000 and July 2010, 113 patients with
squamous cell carcinoma of the vulva were diagnosed and operated on at
Gynecologic Oncology Clinic of Medical University, Pleven. All the patients were
monitored at the same clinic. Individual approach was applied to each patient and
whenever it was possible, more conservative operative techniques were applied.
The probable clinicopathological characteristics influencing the overall survival
and recurrence free survival were analyzed. Univariate statistical analysis and
Cox regression analysis were made in order to evaluate the characteristics, which
were statistically significant for overall survival and survival without
recurrence. A multivariate logistic regression analysis (Forward Wald procedure)
was applied to evaluate the combined influence of the significant factors. While
performing the multivariate analysis, the synergic effect of the independent
prognostic factors of both kinds of survivals was also evaluated. RESULTS:
Approaching individually each patient, we applied the following operative
techniques: 1. Deep total radical vulvectomy with separate incisions for lymph
dissection (LD) or without dissection--68 (60.18 %) patients. 2. En-bloc
vulvectomy with bilateral LD without vulva reconstruction--10 (8.85%) 3. Modified
radical vulvactomy (hemivulvectomy, patial vulvactomy)--25 (22.02%). 4. wide
local excision--3 (2.65%). 5. Simple (total /partial) vulvectomy--5 (4.43%)
patients. 6. En-bloc resection with reconstruction--2 (1.77%) After a thorough
analysis of the overall survival and recurrence free survival, we made the
conclusion that the relapse occurrence and clinical stage of FIGO were
independent prognostic factors for overall survival and the independent
prognostic factors for recurrence free survival were: metastatic inguinal nodes
(unilateral or bilateral), tumor size (above or below 3 cm) and lymphovascular
space invasion. On the basis of these results we created two prognostic models:
1. A prognostic model of overall survival 2. A prognostic model for survival
without recurrence. CONCLUSIONS: Following the surgical staging of the disease,
were able to gather and analyse important clinicopathological indexes, which gave
us the opportunity to form prognostic groups for overall survival and recurrence
free survival.
PMID- 27514128
TI - [LASER CONISATION VS. COLD KNIFE CONISATION FOR CIN].
AB - For the period of 5 years (2008-2012) at the outpatient department and the
operation theater of Tokuda hospital 280 conisations were done--135 lasers and
145 cold knifes. Indications for the operation were common, with no specific
choice for the aim of comparison. All patients had proven colposcopic or
histologic dysplasia of the cervix. The operations were performed 2 or 3 days
after menstruation. Laser conisations received local anesthesia and were not
hospitalized. Cold knife conisations were done at the operation theater under
regional anesthesia, they attended the hospital for 24 hours, had vaginal
tapenade and urethral catheter. Indications for the operation were as follows:
CIN I-14 laser and 38 cold knife conisations; CIN II-30 laser and 28 cold knife
conisations; CIN III--CIS-73 laser and 74 cold knife conisations. The follow up
is: 2 months after the operation-colposcopy and every 3 months afterwards--PAP
smear and colposcopy for 1 year.
PMID- 27514129
TI - [CLINICO-MORPHOLOGICAL STUDY OF 68 CASES OF INVASIVE ENDOCERVICAL
ADENOCARCINOMA].
AB - Recent studies have demonstrate an increase in both relative and absolute
frequency of the cervical adenocarcinoma (ECA) with incidence about 10-25% of all
cervical malignancy. THE AIM: clinicopathological study of invasive ECA.
MATERIALS AND METHOD: From 2007 to end of 2011, 68 cases of invasive ECA were
collected. The tumors were classified according the WHO classification of tumors
of Tumors of the Female Reproductive Organs 2014. RESULTS: The distribution of
different histological types of ECA was as follow: Usual type-29 (42.65%);
Endometroid type-15 (22.06%); Adenosquamous type-15 (22.06%); Villoglandular type
6 (8.82%); Signet-ring type-2 (2.94%); and Intestinal type-1(1.47%). The middle
age of patients was 45 years and varied in large diapason 27-73 years. A
synchrony presence of CIN and glandular dysplasia even to AIS in some cases with
usual and adenosquamous type were detected. The clinical and morphological data
of every type ECA was analised.
PMID- 27514130
TI - [CONSERVATIVE MANAGEMENT OF PLACENTA ACCRETE DURING VAGINAL DELIVERY].
AB - Conservative management of placenta accrete consists in leaving the entire
placenta accreta in situ after vaginal delivery of the fetus. This behavior
requires active monitoring the vital signs of mother, genital status and
paraclinical indicators for an extended period after birth. Monitoring is
suspended after full absorption of the placenta. The success of the conservative
approach depends on: the adopted protocol formanagement of placenta accreta,
whether the diagnosis is known before birth, the possible of application
techniques, reducing blood flow to the uterus, keeping the placental period and
others. The smallest success with vaginal birth, is when the diagnosis of
placenta accreta is not know in advance and proceed with aggressive attempts to
extract the placenta, followed by profuse bleeding from the uterus. As additional
methods of securing conservative management is reported use of Methotrexate, with
unproven effectiveness and embolization of a. Iliaca interna and a. uterine,
which require a qualified team and have a lot of complications. Complications of
conservative management of placenta accreta are: febrility and genital bleeding,
which are the cause of late hysterectomy in about 35% of cases. lnfestion may be
not always prevent by application of broad spectrum antibiotics. Late bleeding is
usually associated with an active inflammatory process. Low-grade and low grade
temperature increase of leukocytes and CRP may be due to necrotic changes in the
placenta without the infection process. Tracking involution of the placenta is
through abdominal and transvaginal ultrasound, magnetic resonance, using
hysteroscopy through serial monitoring the level of hCG. From literature data the
time for resorption of the placenta varies from 4 months to 1 year. It is
essential to determine the time when it is safely to extract the placenta move in
order to prevent late complications of conservative management. Our experience
and some authors suggest that there may be instrumental extraction under
ultrasound control at 8-10 days after birth.
PMID- 27514131
TI - [Medical and social aspects of interruption of the pregnancy].
PMID- 27514132
TI - [CONSERVATIVE TREATMENT OF MAYER-ROKITANSKY-KUSTER-HAUSER SYNDROME. REVIEW OF
LITERATURE AND OUR EXPERIENCE].
AB - Mayer-Rokitansky-Kuster-Hauser syndrome is a part of the group of abnormalities
known as "Anomalies of the fusion of the Mullerian ducts". It is characterized by
normal development of breasts and hairs, normal appearance of external genitalia,
normal feminine genotype (46XX), normal FSH, LH, E2 and Test. levels, normal
ovaries and congenital absence of uterus and the whole or the upper two thirds of
the vagina. It is observed in about 15% of the cases with primary amenorrhea and
the incidence is about 1:4500-6000. Etiologycal factors such as lack of
estrogen/gestagen receptors, deletions or mutations of genes that stop the
fusion, as well as the activation of anti-Mullerian hormone (AMH), are
considered. The etiology is being explored but there is no consensus yet. The
diagnosis is confirmed during a clinical examination, which takes place because
of a primary amenorrhea (often happening at the age of 16), and the absence of a
uterus and vagina is proved. The therapy should be handled by a multidisciplinary
team including obstetrician, trained midwife, psychologist, specialist in imaging
and psycho-sexual counseling. The idea for surgical creation of vagina
(neovagina) dates many years ago. The first known documents date back to 1817 and
over the years a variety of methods are offered usage of amnion, dura mater,
peritoneum, skin grafts, different parts of the intestine, cellulose, etc. The
first method of non-surgical treatment is offered by the Czech gynecologist
Frank. His ambition was to build a vagina by gradual dilatation of the tissue
while applying dilatators with successively increasing length and thickness. The
method was further developed by Ingram (1981) and nowadays by Edmonds (2012). He
reported about 245 patients treated during the last 12 years by his team. 232 of
them had a success in anatomic aspect (95%), 13 did not complete the treatment
due to psychological or cultural problems. The experts from American College of
Obstetricians and Gynecologists include in their "Committee Opinion" from May
2013 the following lines: "Non-surgical creation of the vagina is the appropriate
first line approach in most patients". Briefly is presented our experience in
this field--14 girls at the age of 16-18, successfully treated with dilatation in
the III Gynecology Clinic in University hospital "Maichin dom", Sofia, Bulgaria.
PMID- 27514133
TI - [ENDOMETRIAL POLYPS--CLINICOPATHOLOGICAL FEATURES OF MALIGNANCY AND THERAPEUTIC
ATTITUDE].
AB - Endometrial polyps represent a localized overgrowth of the endometrium,
projecting above the epithelium. Endometrialpolyps maybe single or multiple, may
measure from a few millimeters to centimeters, and maybe sessile or pedunculated.
The use of transvaginal ultrasound is inevitably entailing a significant increase
in the number of women diagnosed with endometrial polyps. Endometrial polyps are
usually benign although some may be precancerous or cancerous. The prevalence of
malignant change in EMPs varies from 0.8 to 8%. Hysteroscopic polypectomy is
effective and safe as both a diagnostic and therapeutic intervention. It remains
the gold standard for treatment. Given that most polyps are not malignant, there
is an option for expectant management with no intervention. It is impotant to
evaluate the prevalence of endometrial premalignant and malignant polyps in
premenopausal and postmenopausal women, as well as the clinical, ultrasound, and
hysteroscopic factors associated with malignancy. Asymptomatic postmenopausal
polyps are unlikely to be malignant and observation is an option after discussion
with the patient.
PMID- 27514134
TI - [CO2 LASER SURGERY IN GYNECOLOGY--NEW HORIZONS].
AB - AIM: Short history of laser procedures in gynecology, benefits and new horizons.
PMID- 27514135
TI - [LAPAROSCOPIC TREATMENT OF INTRALIGAMENTAL LEIOMYOMA PER MAGNA].
AB - Uterine myoma is the most frequent benign tumor of female organs.
Intraligamentary myomas in the broad ligament are rare. We present a case of 50
years old patient with 22 cm intraligamentary myoma with cystic degeneration, who
is referred to the Gynecological Department of Ob/Gyn Hospital "Dr. Shterev" with
complains of severe pain. This case is interesting for its rareness and
diagnostic dilemma, because degenerative myomas can imitate malignant mass. Total
laparoscopic hysterectomy with ablastic vaginal morcellation of the specimen in
endobag was performed. The patient was discharged from the clinic next day.
PMID- 27514136
TI - [NEW APPROACH IN DIAGNOSTIC ALGORITHM OF AN INFECTIOUS AGENTS (PARVOVIRUS B19 AND
CHLAMYDIA TRACHOMATIS) INVOLVED IN THE DEVELOPMENT OF PATHOLOGICAL PREGNANCY].
AB - Viral infections during pregnancy, along with some form of accompanying pregnancy
diseases such as diabetes, cardiovascular, gastrointestinal, kidney and others,
are a major cause of arising complications and mortality of mother and fetus.
AIM: To improved the laboratory diagnostic approach in the study of women with
pathological pregnancy, including improve treatment and prognostic character of
the outcome of pregnancy, with the inclusion of two infectious agent parvovirus
B19 and Chlamydia trachomatis. To determine types of anemia in pregnant women
with parvovirus B19 and Chlamydia trachomatis infection and to select the correct
therapeutic approach. MATERIALS AND METHODS: A total 36 serum samples from
pregnant women with anemia (n = 22), nonimmune hydrops fetalis (n = 8) and fetal
ascites (n = 6) were tested. The study included three newborns (n = 3), tested on
the occasion of a possible maternal-fetal infections. The serological (indirect
ELISA tests) and molecular (B19V-PCR test) methods were used. In anemic pregnant
women were evaluated iron homeostasis parameters with CLIA, AAS and NEPH methods.
RESULTS: In 6/36 (16.66%) patients B19V-IgM positive result was detected. Among
the study patients with anemia, non-immune hydrops fetalis and fetal ascites
incidence of proven B19V-IgM antibodies was 18.18% (4/22), 12.5% (1/8) and 16.66%
(1/6), respectively. Protective B19-IgG antibodies in 25/39 (64.10%) samples were
found. A positive PCR signal was showed in all patients with positive B19V-IgM,
and 1 patient with anemia and positive B19V-IgG result. The three newborns were
positive for B19V-IgG antibodies (maternal) and negative for acute viral
infection. Present Chlamydia trachomatis infection in 6/36 (16.66%) and past
infection in 5/36 (13.89%) patients was demonstrated. The anemia was evaluated as
iron-deficiency according to low hepcidin levels 2.54 +/- 0.4 MUg/I compared to
pregnant control group which included women without anemia 25.9 +/- 2.8 MUg/I.
CONCLUSION: In view of the varied transmission B19V and the wide range of
complications arising as a result of chlamydia, screening for these viral agents
of pregnant women and women of childbearing age is an important approach for
monitoring of pregnancy.
PMID- 27514137
TI - [INFLUENCE OF STIMULATION PROTOCOL ON MATURITY AND MORPHOLOGICAL FEATURES OF
OOCYTES IN PATIENTS WITH LOW OVARIAN RESERVE: STUDY OF 72 IVF/ICSI TREATMENT
CYCLES].
AB - The current study presents the results of a retrospective and prospective
observation of the maturity and morphological features of the oocytes and the way
they are influenced by the therapeutic approaches and the protocol for controlled
ovarian hypersimulation (COH) in patients with low ovarian reserve. MATERIALS AND
METHODS: The study includes 184 oocytes, derived from 72 patients with low
ovarian reserve involved in an infertility treatment program through in vitro
fertilization from February 2011 to February 2014. The applied therapeutic
approaches and COH protocols are microdose agonist short protocol, antagonist
short protocol, mild stimulation protocol and natural cycle in vitro
fertilization. RESULTS: Our study hasn't found a statistically significant
dependence between the applied ovarian stimulation protocol and the maturity and
morphology.
PMID- 27514138
TI - [POSSIBILITIES AND LIMITATIONS ANALYSIS OF SCREENING IN PREGNANT WOMEN FOR DOWN
SYNDROME AND OTHER COMMON CHROMOSOMAL DISORDERS OVER A PERIOD OF TWO YEARS].
AB - Maternal biochemical screening and the new non-invasive prenatal screening tests
as well as prenatal diagnostic tests as tools to fight serious chromosomal
diseases have their possibilities and limitations. The article presents analysis
of the results in 7 201 pregnant women: 4426 first trimester and 2775 second
trimester biochemical screening, together with 994 calculated integrated risks
performed in the Laboratory of medical genetics in 2013 and 2014 year. A matter
of mass screening in both periods is the criterion of efficiency--financially
justified reasons on the basis of comparison "sensitivity" of different
approaches. First trimester screening revealed 5 (71.42%) cases of chromosomal
disease and 1 (14.28%) case with large congenital anomaly. From second trimester
biochemical screening 3 (60%) cases were revealed. Chromosomal pathology in
pregnant women with calculated integrated risk was found in 7 (70%) cases. From a
total of 22 screened pregnant women with prenatal or postnatal verified diagnosis
of Down syndrome, Edvards, Patau or Turner, highest detection rate is found in
first trimester screening--6 of 7 (85.7%). Contingent approach is most widely
used in Europe and we confidently recommend it.
PMID- 27514139
TI - [LAPAROSCOPIC BURCH COLPOSUSPENSION WITH PARAVAGINAL REPAIR].
AB - Genuine urinary stress incontinence (GUSI) is defined by the International
Continence Society (ICS) as involuntary loss of urine coincident with increased
intra-abdominal pressure in the absence of a detrusor contraction or an over
distended bladder. If the patient demonstrates a cystocele secondary to a
paravaginal defect, a paravaginal defect repair should be performed before the
colposuspension. The laparoscopic retropubic colposuspension gained popularity
because of its reported advantages of improved visualization, shorter hospital
stay, faster recovery and decreased blood loss. A review of our experience
revealed 11 of 24 patients had a Burch urethropexy and paravaginal repair and 13
of 24 a Burch urethropexy alone. Average operative time was 80 min, estimated
blood loss of less than 50 ml and hospital stays less than 48 h.
PMID- 27514140
TI - [ANTENATAL APPLICATION OF CORTICOSTEROIDS IN LATE PRETERM BIRTHS].
AB - The aim of the following study is to present the current evidence of antenatal
use of corticoids in premature birth. The benefits of antenatal use of
corticosteroids after 34 week of gestation is still a process of discussion.
PMID- 27514141
TI - [CALCIUM LEVELS IN URINE SAMPLE IN PREGNANT WOMEN WITH PREECLAPMSIA].
AB - Hypertensive disorders during pregnancy are still leading cause for maternal and
perinatal death. Calcium metabolism is impaired significantly in women with
preeclampsia. Measurement of calcium levels in 24 hours urine sample is easy,
modern, fast and not expensive predictive test to reveal women in high risk of
developing preeclampsia in late pregnancy. The severity of condition strongly
correlates with decrease level of calcium excretion in urine.
PMID- 27514142
TI - [BENEFITS AND RISKS AT IMPLEMENTATION OF PROPHILACTIC VACCINES FOR CERVICAL
CANCER].
AB - The aim of this review is to present the benefits and risks of the implementation
of prophylactic vaccines for cervical cancer. The classical understanding of
human papilloma virus (HPV) infection and its role for the cervical oncogenesis,
as well as, the place of prophylactic HPV vaccines are discussed. Results
concerning the effectiveness of vaccines 10 years after their introduction and
data about their safety are presented. Reports of the use in practice of the new
9-valent HPV vaccine and the first results of its implementation are studied.
PMID- 27514143
TI - [PREGNANCY AND DELIVERY IN A PATIENT WITH CHARCOT-MARIE-TOOTH DISEASE].
AB - We report a case of a 34 years old primigravida with Charcot-Marie-Tooth disease
(CMTD). The course of pregnancy was uneventful with no deterioration of symptoms
due to the disease. Performed amniocentesis showed healthy fetus. Planned
cesarean section with spinal anesthesia was performed because of the restricted
pelvis. The possible issues of combination pregnancy and CMTD are discussed.
PMID- 27514144
TI - [DISSEMINATED PERITONEAL LEYOMYOMATOSIS AFTER LAPAROSCOPIC MORCELLATION--A CASE
REPORT].
AB - We presented a case of 41-year-old patient underwent two laparoscopic
Myomectomies and current laparotomy regarding suspection of necrotic leiomyoma.
Intraoperative finding was suggestive of disseminated malignancy, but gefrir
study showed benign smooth muscle tumors. The patient underwent total
hysterectomy with right adnesectomy and total omentectomy. After histological and
immunohistochemical study of the entire macroscopic material the final diagnosis
was disseminated peritoneal leiomyomatosis. This disease is rare, but in recent
years, in connection with the widespread introduction of laparoscopic surgery the
reports of disseminated peritoneal leiomyomatosis occurring after laparoscopic
morcellation, were frequent.
PMID- 27514145
TI - [LOCALLY ADVANCED CERVICAL CANCER IN THE PUERPERIUM--CASE REPORT].
AB - The cervical cancer is the most common gynaecological neoplasma during pregnancy.
The average frequency during pregnancy and 1 year post partum is around 1 case
per 2 200 pregnancies. The authors present a case of locally advanced cervical
cancer (IV stage), diagnosed 30 days after Cesarean section. 5-years survival of
this stage is 15%.
PMID- 27514146
TI - [LAPAROSCOPIC TREATMENT OF PRIMARY ABDOMINAL PREGNANCY: A CASE REPORT AND REVIEW
OF THE LITERATURE].
AB - Abdominal pregnancies are 1.4% of all ectopic pregnancies. They are mostly
complicated and usually managed by laparotomy, but laparoscopy is an alternative
method which some surgeons perform instead of laparotomy, especially in early
pregnancy. We reported a 29 year old woman with supra pubic pain and vaginal
bleeding. After sonographic evaluations, ectopic pregnancy was diagnosed and the
patient underwent laparoscopic surgery for termination of pregnancy. Laparoscopy
is a successful alternative method of surgery for abdominal pregnancies in first
trimester.
PMID- 27514147
TI - [THE ROLE OF MOTHER'S MILK AND BREAST FEEDING. MEDICAL PROBLEMS DURING THE
LACTATION PERIOD LACTOBACILUS FERMENTUM--A NEW APPROACH TOWARDS THE PREVENTION
AND THE TREATMENT OF ACUTE AND SUBACUTE MASTITIS].
AB - Breast feeding provides a lot of short and long-term benefits for the mother and
the baby. It prevents the baby of gastrointestinal, urinary and respiratory
infections, atopical conditions and assures long-term protection of
cardiovascular and metabolic diseases. The breast feeding decreases the risk for
the mother of ovary and breast carcinoma and creates a positive emotional bond
between the mother and the baby Mother's milk is a species specific; its content
is relatively stable regardless of mother's age race, way and place of living.
Mother's milk is not sterile. There is a 10 year international trial held in
Spanish and Finnish universities. It has identified and count all microorganisms
in mother's milk (more than 700) and proved that their content and quantity
varies according the age of the baby. Mother's milk is a source of lactobacillus
for baby's intestines and most of them have probiotic potential. Lactobacillus
fermentum Lc40 (hereditum) is isolated from mother's milk. It has a good
viability in gastrointestinal system, high level of adhesion to intestinal
epithelium cells, produces glutation--strong antioxidant, good antibacterial
activity to entero-pathogens and potential of increasing the immunologic
response. Clinical trials reveal that Lactobacillus fermentum plays important
role to microflora balance of mother's milk in mastitis during lactation. Many
trials estimating the efficiency of lactobacillus fermentum in prevention and
treatment of acute and subacute mastitis have been carried out. The results of
them open a new door in front of us in the treatment of these conditions-
treatment with probiotics instead of antibiotics.
PMID- 27514148
TI - Dentistry as an Endurance Sport.
PMID- 27514149
TI - CDA Well-Being.
PMID- 27514150
TI - Dental Problems.
PMID- 27514151
TI - Mrs. Jellyby and the Hot Rock.
PMID- 27514152
TI - The Oral Microbiome: Critical for Understanding Oral Health and Disease.
PMID- 27514153
TI - Dental Calculus and the Evolution of the Human Oral Microbiome.
AB - Characterizing the evolution of the oral microbiome is a challenging, but
increasingly feasible, task. Recently, dental calculus has been shown to preserve
ancient biomolecules from the oral microbiota, host tissues and diet for tens of
thousands of years. As such, it provides a unique window into the ancestral oral
microbiome. This article reviews recent advancements in ancient dental calculus
research and emerging insights into the evolution and ecology of the human oral
microbiome.
PMID- 27514154
TI - Subgingival Microbiome Shifts and Community Dynamics in Periodontal Diseases.
AB - High-throughput 16S rRNA gene sequencing has allowed the characterization of
subgingival microbiome shifts from health to periodontitis identifying health
associated, periodontitis-associated and core species, which preserve their
proportions from health to disease. The development of gingivitis is also
characterized by distinct shifts. Microbiome shifts resemble microbial
successions and result from interspecies interactions and community adaptation to
the changing environment as inflammation ensues. Gingivitis-associated and core
species are proposed as likely mediators of microbiome transitions.
PMID- 27514155
TI - Understanding Caries From the Oral Microbiome Perspective.
AB - Dental caries is a major disease of the oral cavity with profound clinical
significance. Caries results from a transition of a healthy oral microbiome into
an acidogenic community of decreased microbial diversity in response to excessive
dietary sugar intake. Microbiological cultivation, molecular identification, gene
expression and metabolomic analyses show the importance of the entire microbial
community in understanding the role of the microbiome in the pathology of caries.
PMID- 27514156
TI - Uncultured Members of the Oral Microbiome.
AB - Around one-third of oral bacteria cannot be cultured using conventional methods.
Some bacteria have specific requirements for nutrients while others may be
inhibited by substances in the culture media or produced by other bacteria. Oral
bacteria have evolved as part of multispecies biofilms, and many thus require
interaction with other bacterial species to grow. In vitro models have been
developed that mimic these interactions and have been used to grow previously
uncultivated organisms.
PMID- 27514157
TI - Preservation of Property: A Critical Obligation.
PMID- 27514158
TI - A Patient's Right to Access Records Q-and-A.
PMID- 27514159
TI - Undertreatment, an Ethical Issue.
PMID- 27514160
TI - A Dentist's Guide to Fitness.
PMID- 27514161
TI - [COMPARISON OF LAPAROSCOPIC ASSISTED VAGINAL HYSTERECTOMY AND VAGINAL
HYSTERECTOMY FOR BENIGN DISEASES AND LESIONS OF THE FEMALE GENITAL SYSTEM].
AB - OBJECTIVE: To compare the efficacy of laparoscopic assisted vaginal hysterectomy
(LAVH) and vaginal hysterectomy (VH) carried out on the occasion of non-malignant
diseases and lesions of the female genital system, by assessing the: operative
time, price, blood loss, hospital stay, intra and postoperative complications,
satisfaction of the patient. MATERIALS AND METHODS: The study included 187 women
aged 38-71 years, with hysterectomy with or without salpingo-oophorectomy by LAVH
58 (31%) women or VH-129 (69%) women, on the occasion of non-malignant diseases
and lesions of the female genital system. The patients are including in the study
groups according to including and excluding criteria. Operation preparation,
research and intra and postoperative follow-up of patients in both groups were
the same. Standard, as performance is the surgical technique in both groups. The
indicators are analyzed with the statistical program SPSS 10.1 for windows. Shi
square test, Fisher exact test were used in appropriate cases. RESULTS: No
significant difference between groups in terms of age (LAVH 48.7 +/- 3.2 years;
VH 52.7 +/- 4.8 yrs), live births (1-3)/2 (1-2), total weight (62.6 kg/59 +/- 7.2
kg) weight of the uterus (227 +/-116.5/234 +/-: 68.3). Most often Indications for
LAVH are: CIN/CA in situ coli uteri--16.1%; myoma uteri--22.5%; ovarian tumor-
15.5%, etc. Indications for VH: genital prolapse--53.5%; CIN/CA in situ--14.7%;
recurrent endometrial polyp--14%, etc. Operative time: LAVH (126 +/- 18.2), VH
(68 +/- 11.1), (p <= 0.05). Intraoperative blood loss: LAVH (16 +/- 7 average
drop in hemoglobin Hb), VH (10 +/- 5 decline in Hb array) (p <= 0.05). We didn't
find out significant differences between the patients of both groups in terms of
hospital stay and satisfaction with the carried out operation. Intraoperative
complications are more in the LAVH group and almos absence in VH group. Post
operative complications occur without statistical differences (we exclude urinary
infections) in both groups studied. CONCLUSIONS: In our study the VH showed
better or equal results in the studied indicators in comparison with LAVH,
therefore it is surgical intervention of choice compared to LAVH for removal of
the uterus with or without the adnexa in non-malignant diseases and lesions of
the female genital system. LAVH is the right choice in comparison with VH only in
ovarian tumors and when we expected problems in women small pelvis.
PMID- 27514162
TI - [LAPAROSCOPIC PELVIC LYMPNADENECTOMY OF EARLY ENDOMETRIAL CANCER].
AB - Lymphadenectomy has traditionally been performed using large incisions during
laparotomy. Since the initial report by Dargent and colleagues in the late 1980s,
laparoscopic lymphadenectomy has been utilized in the management of gynecologic
malignancies. After Dargent's description of the first pelvic lymphadenectomy
performed laparoscopically, Nezhat et al. described the first para-aortic
lymphadenectomy performed laparoscopically forcancer of the uterine cervix. Many
raports since have described the safety and effectiveness of laparoscopic
lymphadenectomy for gynecologic malignancies.
PMID- 27514163
TI - [OBESITY AND GYNECOLOGICAL CANCER].
AB - An analysis of 329 patients with gynecological cancer, 120 of them were without
obesity and 209 of them were with obesity. Only 36.47% of the cases were with
normal weight. There is a trend of increasing obesity with age, with a peak in
the age group 60-69 years. The distribution of patients according to BMI and
stage of the disease there is a downward trend in the obesity with increasing
stage. In both groups of patients (with and without obesity), the volume and type
of surgery were carried out depending on the type of tumor process (localization)
and stage of the disease. Radical histerectomy with pelvic lymph node dissection
(with or without omentectomy) is carried out in 141 patients, of which only 6
were of normal weight, and 135 patients (95.7%) were of different stage of
obesity. Total hysterectomy with pelvic lymph node dissection (with or without
omentectomy) is carried out in 123 patients, of which only 2 were of normal
weight, and 121 patients (98.4%) were of different stage of obesity. Our results
show that the volume of surgery in patients with gynecological cancer does not
depend the obesity and depend the stage of disease.
PMID- 27514164
TI - [PRIMARY CYTOREDUCTIVE SURGERY VERSUS NEOADJUVANT CHEMOTHERARY IN TREATMENT OF
ADVANCED OVARIAN CANCER (STAGE III C-IV). OUR AND FOREIGN EXPERIENCE].
AB - INTRODUCTION: The advanced ovarian cancer usually have bad prognosis. The main
methods for treatment of these types of tumors are: primary cytoreductive surgery
and platin-based chemotherapy. AIM: Our aim was to evaluate our and foreign
experience in treatment of advanced ovarian cancer stage III C--IV treated by
neodjuvant chemotherapy followed by cytoreductive surgery and patients treated by
primary cytoreductive surgery followed by adjuvant chemotherapy. We wanted to
research the survival rate, postoperative adverse effects, mortality rate, the
size of residual tumor and the metastases in these patients. MATERIAL AND
METHODS: We researched for 10 years period--50 patients treated by primary
cytoreductive surgery and 50 patients treated by neoadjuvant chemotherapy.
RESULTS: The postoperative adverse effects and mortality rate are lower by
neoadjuvant chemotherapy followed by cytoreductive surgery. The most important
independent prognostic factor for overall survival rate was the lack of residual
tumor in both types of treatment. CONCLUSION: The neoadjuvant chemotherapy
followed by cytoreductive surgery in ovarian cancer stage III C--IV is considered
as a standard treatment.
PMID- 27514165
TI - [ADHERING TO MEDICAL STANDARTS, EVIDENCE-BASED STAGING IN GYNECOLOGICAL CANCER].
AB - Among the key factors that influence the survival of patients is adherence to
medical treatment standards. Indicators are assessing the degree of adherence to
medical standards and represent the relative shares (%) of patients who fulfilled
the relevant aspect of any subject. Data from the BNCR of 9842 cases of patients
with malignant diseases of the female reproductive diagnosed in 2011-2013 in
Bulgaria has been analyzed. Patients with tumors of the vulva were incorrectly
staged in 15% to 30% of the cases, and those with vaginal tumors were incorrectly
staged in 20% to 23% of cases. In patients with malignant tumors of the cervix
incorrect staging was established in 19% to 47% of the cases. Patients with
tumors of the uterus were incorrectly staged in 6% to 26% of the cases. Among the
patients with ovarian tumors were incorrectly staged in 18% to 43%. Our results
show that one in three patients with gynecological cancer in Bulgaria was
incorrectly staged. We recommend using the current TNM and FIGO systems.
PMID- 27514166
TI - [RECONSTRUCTIVE AND COSMETIC SURGERY IN TREATMENT OF VULVAR CANCER].
AB - The aim of our research work was to show our results in the field of
reconstructive and cosmetic surgery for vulvar cancer. MATERIAL AND METHODS: We
evaluated 18 patients for 10 years period. RESULTS: We applied all surgical
techniques that are possible at the moment in the world: laps from mons pubis,
rhomboid flaps, myocutaneous flaps from gluteal region. We used surgical
techniques with the following muscle groups: musculus gracilis, musculus gluteus
maximus, musculus tensor fasciae latae, musculus rectus abdominis. CONCLUSIONS:
With our research work we tried to better the quality of life of our patients, to
achieve better esthetic and cosmetic effect after very radical surgical
interventions connected with vulvar cancer.
PMID- 27514167
TI - [COMORBIDITIES IN PATIENTS WITH ONCOGYNECOLOGICAL CANCER].
AB - Comorbidities may directly affect the prognosis of the disease of interest or may
indirectly affect the prognosis by affecting the choice of treatment. The aim of
this study is to determine comorbidities in pacients with gynecological cancer.
The study included 100 consecutive pacients for the period 01.01.2014-08.-5.2014
in Gynecological department of Specialized Hospital for ActivTratament in
Oncology. The most common disease are arterial hipertony diabetes and obesity. In
most patients, establish one or more accompanying illnesses that increase with
age.
PMID- 27514168
TI - The role of laparoscopy in the case of suspected advanced ovarian cancer
(ascites, CA-125)].
PMID- 27514169
TI - [A case of isolated massive presacral lymphatic metastasis in stage I uterine
cervical cancer].
PMID- 27514170
TI - [Labial fusion in postmenopausal women--a clinical case].
AB - Labial fusion is benign genital disorder, which more frequent in children at 6
years old and less in women in reproductive and postmenopausal age. It can be
congenital or acquired condition. Its etiology is unclear. The low serum estrogen
concentration is the basic cause of labial fusion. As a result of physiological
hypoestrogenism in the vulvar skin and mucosa come on atrophic changes, which
together with the chronic inflammatory changes lead to labial adhesia with
subsequent partial or total obstruction of the vagina and/or the urethra. The
treatment can be conservative or surgical depending on the degree of labial
fusion. We perform two clinical cases respectively of total and partial
vulvarsynechiae in postmenopausal women. The clinical picture of the patient with
total synechiae is represented by a difficult and prolonged micturition and
urinary incontinence, while in patients with partial synechiae is represented by
an inability to carry out sexual intercourse.
PMID- 27514171
TI - Promises, promises.
PMID- 27514172
TI - The future is bright.
PMID- 27514173
TI - [Not Available].
PMID- 27514174
TI - REPLY FROM FINTAN HOURIHAN.
PMID- 27514176
TI - Agenda setter.
PMID- 27514175
TI - [Not Available].
PMID- 27514177
TI - Understanding your practice's costs.
PMID- 27514178
TI - Establishing expectations.
PMID- 27514179
TI - Baby steps: a systematic approach to the infant oral health visit.
PMID- 27514180
TI - Clinical and radiographic assessment of maxillary canine eruption status in a
group of 11- to 14-year-old Irish children.
AB - OBJECTIVE: The aim of this study was to investigate the prevalence of potentially
ectopic maxillary canines and associated dental features in a group of 11- to 14
year-old children. PARTICIPANTS: Examination took place of a normal dlistribution
of Irish schoolchildren age between I11 and 14 years in order to record the
number of subjects with indications for radiographic investigation of .
potentially ectopic maxillary canines. METHODS: Those subjects identified
subsequently underwent radiographic examination and the number of subjects with
potentially ectopic maxillary canines was established. Correlations within the
latter sub-sample with anomalous or missing laterals, type of occlusion and
female:male ratio were investigated. RESULTS: A total of 480 children were
screened. Of the children aged 11 to 14 years, 32 (6.6%) had clinical indications
for radiographic examination of potentially ectopic maxillary canines according
to the criteria that had been set out. There were 11 maxillary canines, in 10
subjects, that had an unfavourable position for eruption and were considered to
be potentially ectopic, and so 1.1% of the maxillary canines reviewed in this
study showed a potential ectopic eruption position. CONCLUSIONS: The prevalence
of potentially ectopic maxillary canines and associated dental features in an
Irish population was found to be similar to those in other countries, and the
practice of careful supervision and early diagnosis of any eruption disturbances
of the permanent maxillary canines continues to be considered important due to
the risks associated with their eruption.
PMID- 27514181
TI - Primary Ewing sarcoma of the coronoid process of mandible.
AB - Ewing sarcoma (ES) is a rare, primary malignancy of the bone that occurs mainly
in childhood and early adolescence. ES usually occurs in long bones of the axial
skeleton. Although uncommon in the jaws, ES at this site is most likely to occur
in the posterior mandible. The outcome for patients with localised disease has
improved over the decades, due to better combination chemotherapies and better
methods of local control. We present the clinicopathologic features and
management of a case of ES that developed in the left coronoid process of the
mandible of a 31-year-old male. Chemotherapy and, later, a segmental
mandibulectomy were used to achieve local control. A fibula-free flap repair was
performed with good aesthetic results. This case elucidates the importance of the
interdisciplinary approach required for the evaluation and treatment of this
aggressive neoplasm.
PMID- 27514182
TI - More than a professional body.
PMID- 27514183
TI - Evaluation of certain food additives and contaminants. Eightieth report of the
Joint FAO/WHO Expert Committee on Food Additives.
AB - This report represents the conclusions of a Joint FAO/WHO Expert Committee
convened to evaluate the safety of various food additives and contaminants and to
prepare specifications for identity and purity. The first part of the report
contains a brief description of general considerations addressed at the meeting,
including updates on matters of interest to the work of the Committee. A summary
follows of the Committee's evaluations of technical, toxicological and/or dietary
exposure data for seven food additives (benzoates; lipase from Fusarium
heterosporum expressed in Ogataea polymorpha; magnesium stearate;
maltotetraohydrolase from Pseudomonas stutzeri expressed in Bacillus
licheniformis; mixed beta-glucanase, cellulase and xylanase from Rasamsonia
emersonii; mixed beta-glucanase and xylanase from Disporotrichum dimorphosporum;
polyvinyl alcohol (PVA)- polyethylene glycol (PEG) graft copolymer) and two
groups of contaminants (non-dioxin-like polychlorinated biphenyls and
pyrrolizidine alkaloids). Specifications for the following food additives were
revised or withdrawn: advantame; annatto extracts (solavnt extracted bixin, ad
solvent-extracted norbixin); food additives containing aluminium and/or silicon
(aluminium silicate; calcium aluminium silicate; calcium silicate; silicon
dioxide, amorphous; sodium aluminium silicate); and glycerol ester of gum rosin.
Annexed to the report are tables or text summarizing the toxicological and
dietary exposure information and information on specifications as well as the
Committees recommendations on the food additives and contaminants considered at
this meeting.
PMID- 27514184
TI - WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fiftieth
report.
AB - The Expert Committee on Specifications for Pharmaceutical Preparations works
towards clear, independent and practical standards and guidelines for the quality
assurance of medicines. Standards are developed by the Committee through
worldwide consultation and an international consensus-building process. The
following new guidelines were adopted and recommended for use. Good
pharmacopoeial practices; FIP-WHO technical guidelines: points to consider in the
provision by health-care professionals of children-specific preparations that are
not available as authorized products; Guidance on good manufacturing practices
for biological products; Guidance on good manufacturing practices: inspection
report, including Appendix 1: Model inspection report; Guidance on good data and
record management practices; Good trade and distribution practices for starting
materials; Guidelines on the conduct of surveys of the quality of medicines;
Collaborative procedure between the World Health Organization (WHO)
prequalification team and national regulatory authorities in the assessment and
accelerated national registration of WHO-prequalified pharmaceutical products and
vaccines; Guidance for organizations performing in vivo bioequivalence studies;
and World Health Organization (WHO) general guidance on variations to multisource
pharmaceutical products.
PMID- 27514185
TI - [Rheumatology: Progress in Diagnosis and Treatments. Editorial: Treatnnt for
rheumatic diseases-present and future].
PMID- 27514186
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: I. Progress in
Diagnostic Method; 1. Autoantibodies in systemic rheumatic diseases].
PMID- 27514187
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: I. Progress in
Diagnostic Method; 2. Imaging in rheumatoid arthritis].
PMID- 27514188
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: II. Differential
Diagnosis; 1. Clinical symptoms and physical findings which differentiate between
rheumatoid arthritis and other diseases].
PMID- 27514189
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: II. Differential
Diagnosis; 2. Differential diagnosis in rheumatic diseases based on laboratory
and radiological findings].
PMID- 27514190
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: III. Rheumatiod
Arthritis and Allied Conditions; 1. Rheumatoid arthritis].
PMID- 27514191
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: III. Rheumatoid
Arthritis and Allied Conditions; 2. Allied Conditions, 1) Spondyloarthritis].
PMID- 27514192
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: III. Rheumatoid
Arthritis and Allied Conditions; 2. Allied Conditions. 2) Polymyalgia
rheumatica].
PMID- 27514193
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: III. Rheumatoid
Arthritis and Allied Conditions; 2. Allied Conditions, 3) Adult Still disease].
PMID- 27514194
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: III. Rheumatoid
Arthritis and Allied Conditions; 2. Allied Conditions, 4) RS3PE syndrome].
PMID- 27514195
TI - [Rheumatology: Progress in Diagnosis and Treatments Topics: IV. Collagen Diseases
Except for Rheumatoid Arthritis and Hot Topics; 1. Systemic lupus erythematosus].
PMID- 27514196
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics; 2. Antiphospholipid
syndrome].
PMID- 27514197
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics: 3. Systemic sclerosis
(Scleroderma)].
PMID- 27514198
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics; 4. Polymyositis and
dermatomyositis].
PMID- 27514199
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics; 5. Vasculitic syndrome].
PMID- 27514200
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics; 6. Mixed connective
tissue disease].
PMID- 27514201
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics; 7. Sjogren's syndrome].
PMID- 27514202
TI - [Rheumatology: Progress in Diagnosis and Treatments. Topics: IV. Collagen
Diseases Except for Rheumatoid Arthritis and Hot Topics; 8. IgG4-related
disease].
PMID- 27514203
TI - [Discussion Meeting on Clinical update in rheumatic diseases].
PMID- 27514204
TI - [Discussion Meeting on "The Journal of the Japanese Society of Internal Medicine"
by looking back on the past].
PMID- 27514205
TI - [Case Report; A case of nephrotic syndrome with Wilson's disease].
PMID- 27514206
TI - [Case Report; A case of adult human herpes virus-6 associated hemophagocytic
syndrome with mixed connective tissue disease].
PMID- 27514207
TI - [Case Report; A case of rhabdomyolysis following water intoxication derived from
both psychogenic polydipsia and syndrome of inappropriate secretion of
antidiuretic hormone (SIADH)].
PMID- 27514208
TI - [Case Report; Primary central nervous system lymphoma mimicking progressive
multifocal leukoencephalopathy in a patient with acquired immune deficiency
syndrome].
PMID- 27514209
TI - [The Cutting-edge of Medicine; Severe fever with thrombocytopenia syndrome in
Japan: challenges for the future].
PMID- 27514210
TI - [The Cutting-edge of Medicine; Rapidly progressive glomerulonephritis].
PMID- 27514211
TI - [The Cutting-edge of Medicine: Hereditary autoinflammatory diseases: diagnosis
and management].
PMID- 27514212
TI - [Series: For Attending Physicians; Seeking to Understand the Diversity of
Medicine; Complex health problems in primary care].
PMID- 27514213
TI - [How Does the Physician Interpret the Patient's Narrative as It Relates to the
Physical Exam?; A case with obesity treated by low carbohydrate diet (LCD)].
PMID- 27514214
TI - [How Does the Physician Interpret the Patient's Narrative as It Relates to the
Physical Exam?; A case of chronic constipation with abdominal pain].
PMID- 27514215
TI - Migrant nurses need more support.
PMID- 27514216
TI - Emulating Emily Rushton's 'climate change journey'.
PMID- 27514217
TI - Negotiating court systems.
PMID- 27514218
TI - Correcting assertions.
PMID- 27514219
TI - MSF seeks expect nurses.
PMID- 27514220
TI - The president comments.
PMID- 27514221
TI - Support for assisted dying.
PMID- 27514222
TI - Equal pay settlement on the horizon?
PMID- 27514223
TI - Vaccinate-or-mask policy 'coercive'.
PMID- 27514224
TI - Nursing loses two of its pioneering spirits.
PMID- 27514225
TI - A nursing journey from Keralas to Christchurch.
PMID- 27514226
TI - Telling the truth about health underfunding.
PMID- 27514227
TI - Nurse migration raises complex issues.
PMID- 27514228
TI - COPD: obstructed lungs.
AB - CHRONIC OBSTRUCTIVE pulmonary diseases (COPD) affect 14 per cent of the
population over 40 years of age. With an ageing population, the number of those
requiring care for COPD is expected to increase, having a significant effect on
health-care resources. COPD is projected to become the third leading cause of
death globally by 2020. This disease has a major impact on economic and social
well-being, and on quality of life. It is regarded as largely preventable but,
once developed, is a progressive and complex condition characterised by frequent
exacerbations and co-morbidities. Smoking is the primary cause of COPD but up to
30 per cent of those with COPD have never smoked. It is increasingly recognised
COPD may have its origins prenatally and in early childhood. Treating
exacerbations, improving exercise capacity, and delaying progression of disease
are key management strategies. No curative or disease modifying therapies are
available. Nurses are essential in providing comprehensive care to patients in
both acute care and for long-term management. They also have a vital role to play
in preserving healthy lung function in the early years of life to reduce the risk
of COPD in older age.
PMID- 27514229
TI - Introducing ePortfolios into nursing schools.
PMID- 27514230
TI - Developing a strategy to make nursing visible.
PMID- 27514231
TI - NZNO pursues payroll problems.
PMID- 27514232
TI - Regional conventions: Influencing health.
PMID- 27514233
TI - Removing barriers to EN employment.
PMID- 27514234
TI - Red Blood Cell Transfusion and Clinical Outcomes in Extremely Low Birth Weight
Preterm Infants.
AB - BACKGROUND: Red blood cell (RBC) transfusion is often considered a life-saving
measure in critically ill neonates. The smallest and least mature infants tend to
receive the largest amount of transfusions. RBC transfusion itself has also been
suggested as an independent risk factor of poor clinical outcome in critical
patients. Our aim is to study if there are associations between RBC transfusion
and in-hospital mortality, short-term morbidities, and late neurodevelopmental
outcome in extremely low birth weight (ELBW) preterm infants. METHODS: A cohort
of ELBW preterm infants admitted to our neonatal intensive care unit from January
2009 to December 2010 were recruited. The number of RBC transfusions within 7
days, 30 days, and 60 days of life were recorded. Clinical outcomes including in
hospital mortality, development of retinopathy of prematurity (ROP), necrotizing
enterocolitis, chronic lung disease, and later neurodevelopmental outcome were
assessed with follow-up of up to 2 years of age. Multivariable logistic
regression was used to estimate the associations between RBC transfusion and
clinical outcomes. RESULTS: A total of 98 ELBW preterm infants survived at the
time of discharge. Of these survivors, the mean numbers of RBC transfusions were
2.5 +/- 1.7, 7.4 +/- 3.1, and 11.3 +/- 4.5 times within 7 days, 30 days, and 60
days after birth, respectively. The number of transfusions within 7 days of life
was correlated with risk of death before 1 month of age (odds ratio: 1.54, 95%
confidence interval: 1.04-2.27, p = 0.03) and the number of transfusions within
30 days was correlated with risk of developing threshold ROP (odds ratio: 1.27,
95% confidence interval: 1.04-1.55, p = 0.02). The number of transfusions within
7 days of life was positively correlated with cognitive performance (Mental
Developmental Index score) at 18-24 months of corrected age. CONCLUSION: RBC
transfusion has a negative impact on survival in ELBW infants. It increases the
risk of developing ROP and affects late neurodevelopment. Decisions of blood
transfusion in these very immature infants should be made cautiously taking these
deleterious results into consideration.
PMID- 27514235
TI - Piezoelectric and Dielectric Properties of Multilayered BaTiO3/(Ba,Ca)TiO3/CaTiO3
Thin Films.
AB - Highly oriented multilayered BaTiO3-(Ba,Ca)TiO3-CaTiO3 thin films were fabricated
on Nb-doped (001) SrTiO3 (Nb:STO) substrates by pulsed laser deposition. The
configurations of multilayered BaTiO3-(Ba,Ca)TiO3-CaTiO3 thin films are designed
with the thickness ratio of 1:1:1 and 2:1:1 and total thickness ~300 nm.
Microstructural characterization by X-ray diffraction indicates that the as
deposited thin films are highly c-axis oriented and large in-plane strain is
determined in BaTiO3 and CaTiO3 layers. Piezoresponse force microscopy (PFM)
studies reveal an intense in-plane polarization component, whereas the out-of
plane shows inferior phase contrast. The optimized combination is found to be the
BaTiO3-(Ba0.85Ca0.15)TiO3-CaTiO3 structure with combination ratio 2:1:1, which
displays the largest domain switching amplitude under DC electric field, the
largest room-temperature dielectric constant ~646, a small dielectric loss of
0.03, and the largest dielectric tunability of ~50% at 400 kV/cm. These results
suggest that the enhanced dielectric and tunability performance are greatly
associated with the large in-plane polarization component and domain switching.
PMID- 27514236
TI - Depression screening for prescribed medications with mental health risk:
Considerations for clinical decision support, workflow redesign, and health
information exchange arrangements.
AB - OBJECTIVE: Depression screening should be increased when prevailing knowledge
underscoring medication-associated mental health risk is highest. Depression
screening in primary care practices when medications with mental health risk were
prescribed was estimated while considering the absence and presence of clinical
decision support systems. MATERIALS AND METHODS: A cross-sectional, descriptive
study using the National Ambulatory Medical Care Survey (NAMCS) data from 2008 to
2010 was conducted. Primary care physician visits were classified based on
whether a medication prescribed had a contraindication, severe warning, moderate
warning, adverse event only, or no documented mental health risk. Adjusted odds
of depression screening for each risk warning level were estimated while
controlling for important sociodemographic factors and presence of computerized
systems for medication warnings and guideline recommendations. RESULTS:
Depression screening at primary care practice visits when medications were
prescribed was 2.1% and increased to 2.8% or higher when medications had a
moderate or severe mental health risk warning or medication-disease
contraindication. Depression screening was increased at visits when at least one
medication was prescribed that had a contraindication (AOR = 6.31, P < 0.001),
severe warning (AOR = 2.04, P = 0.003), or moderate warning (AOR = 2.50, P =
0.012) for mental health risk, but not for mental health adverse event only
warnings alone (AOR = 1.54, P = 0.074). DISCUSSION: Depression screening is
increased when medications were prescribed with a documented mental health risk.
Presence of clinical decision support systems may help discern between minor and
major medication-associated mental health risks. CONCLUSIONS: Appropriately,
positioned warning systems with targeted content, workflow redesign, and health
information exchange may improve depression screening in at-risk patients.
PMID- 27514237
TI - Diagnostic immunohistochemistry through Rosai-coloured glasses.
AB - Over the past three decades, Immunohistochemistry has materially changed the
practice of diagnostic surgical pathology. Foundational observations in this
field were critical to a reasoned assessment of both the risks and opportunities
that immunohistochemistry afforded the surgical pathologist, and our current
practice draws heavily on those early assessments. As we collectively look to and
acknowledge those who recognized the value of this technique and who helped guide
its development as a companion to (not a replacement for) histomorphologic
evaluation, we are drawn to those whose mastery of detail and ability to draw
common patterns from seemingly unrelated phenomena helped define the diagnostic
power of immunohistochemistry. The focus of this review is on one individual, Dr.
Juan Rosai, whose contributions transcend the simple linkage of molecular
observations to morphology, recognizing novel patterns in both form and color
(the latter often the lovely shades of diaminobenzidine), seemingly viewing our
diagnostic world at times through an entirely different lens. By looking at Dr.
Rosai's early work in this field, reviewing a selection of his seminal
observations, particularly in the Immunohistochemistry of thyroid and thymic
neoplasia, revisiting how his special insight is often guided by the work of the
early masters of morphology, and how his mentorship of others has helped shaped
academic surgical pathology practice, perhaps we can get a glimpse through that
lens.
PMID- 27514238
TI - Extending the Clinical Phenotype of Adenosine Deaminase 2 Deficiency.
AB - Adenosine deaminase 2 deficiency is an autoinflammatory disease, characterized by
various forms of vasculitis. We describe 5 patients with adenosine deaminase 2
deficiency with various hematologic manifestations, including pure red cell
aplasia, with no evidence for vasculitis.
PMID- 27514240
TI - Neonatal-Onset Urticaria and Fever.
PMID- 27514239
TI - Antenatal Betamethasone: A Prolonged Time Interval from Administration to
Delivery Is Associated with an Increased Incidence of Severe Intraventricular
Hemorrhage in Infants Born before 28 Weeks Gestation.
AB - OBJECTIVE: To examine the effects of antenatal steroids on severe
intraventricular hemorrhage (IVH) in infants born during the IVH vulnerable
period (<28 weeks gestational age) and to evaluate rates of IVH correlated with
the time interval between treatment or retreatment and birth. STUDY DESIGN: A
total of 429 infants (<28 weeks gestation), who delivered >=24 hours after the
first betamethasone (BMZ) course (2 doses), were divided into groups based on the
interval between the first course of BMZ and delivery: <10 days or >=10 days. The
primary outcome was severe IVH. Multiple regression analyses were performed to
adjust for potential confounders. RESULTS: Three hundred ninety-two infants
delivered after a single BMZ course (312 delivered <10 days; 80 >=10 days). The
incidence of severe IVH was 17% for infants delivered >=10 days and 7% for those
delivered <10 days after a single BMZ course (aOR 4.16; 95% CI 1.59-10.87, P =
.004); 37 infants (born >=10 days from the first BMZ course) received a
second/rescue BMZ course. The incidence of severe IVH among infants receiving a
second/rescue course was 8%, which was similar to the incidence among infants
born <10 days (aOR 1.7; 95% CI 0.41-6.6, P = .48). CONCLUSIONS: In infants born
before 28 weeks gestation, delivery >=10 days from the first BMZ course is
associated with a higher incidence of severe IVH; a second/rescue course may
reverse this effect.
PMID- 27514241
TI - Molluscum Mimicker: Juvenile Xanthogranulomas with Associated Juvenile
Myelomonocytic Leukemia.
PMID- 27514242
TI - Botulinum Toxin Use in Refractory Pain and Other Symptoms in Parkinsonism.
AB - BACKGROUND: Parkinson's disease (PD) and other parkinsonian syndromes are
chronic, progressive neurodegenerative diseases. With advancing disease, both
motor and non-motor symptoms represent a considerable burden and symptom relief
and quality of life improvement become the main goal of treatment. Botulinum
toxins (BTX) are an effective treatment modality for many neurological
conditions. METHODS: To understand the potential usefulness of BTX in this
population, we performed a retrospective chart review of all patients with a
clinical diagnosis of idiopathic PD and atypical parkinsonism who received
treatment with BTX injections in our center from 1995 to 2014 for a variety of
symptoms. Response to BTX was assessed using a subjective Clinical Global
Impression. RESULTS: Records of 160 patients were reviewed. Probable idiopathic
PD was the diagnosis in 117 patients (73.1%). The main indication for BTX
treatment was pain (50.6% of cases). Other indications were the treatment of
functional impairment resulting from dystonia (26.25%), sialorrhea (18.75%),
freezing of gait, and camptocormia. Considering pain as indication, 81% of all
patients with PD reported benefits after the first BTX injections. This benefit
was maintained after the last recorded visit without significant difference in
outcome compared with the first injection (p=0.067). Similar results were
observed in patients with atypical parkinsonism. CONCLUSIONS: Our results confirm
the safety and efficacy of different uses of BTX in the symptomatic treatment of
patients with parkinsonism even in advanced stages of the disease, and suggest
BTX treatment could have a safe and useful role in the treatment of pain in this
population.
PMID- 27514243
TI - Effect of general health screening and lifestyle counselling on incidence of
diabetes in general population: Inter99 randomised trial.
AB - : We aimed to examine the effect of a large population-based multifactorial
screening and lifestyle intervention programme on 10-year incidence of diabetes.
In a randomised trial of the general Danish population initiated in 1999-2001
59,616 men and women aged 30-60years were assigned to a five year screening and
lifestyle counselling programme (n=11,629) or control group (n=47,987) and
followed for ten years in nationwide registers. Intention to treat was applied
and risk of diabetes was modeled by Cox regression and expressed as hazard ratios
(HRs). We found that 1692 individuals had diabetes at baseline. Among 57,924
individuals without diabetes at baseline, 1267 emigrated, 2593 died and 3369
(Intervention group=684, Control group=2685) developed diabetes. We saw no
significant difference in diabetes incidence between the groups after 10-year
follow-up (Grey's test: p=0.22). In the first year of follow-up, incidence of
diabetes was significantly higher in the intervention group than the control
group (HR=1.68, 95%CI 1.29 to 2.29). We observed no difference in incidence of
diabetes between the groups in the follow-up intervals from 1 to 6years or after
6-10years (HR=0.94, 0.83 to 1.06; HR=1.03, 0.91 to 1.17). Inviting the general
population to participate in a repeated screening and lifestyle counselling
programme over five years did not result in lower incidence of diabetes after
10years of follow-up. As expected, significantly more individuals were diagnosed
with diabetes in the intervention group during the first year, but this was not
followed by a decrease in the following years. TRIALS REGISTRATION: Clinical
trials NCT00289237.
PMID- 27514244
TI - The role of food insecurity in developmental psychopathology.
AB - Food security is a condition achieved when all members of a household have access
to adequate food at all times for a healthy, active lifestyle. As of 2014, 14% of
households in the United States were food insecure. Previous research has
suggested that household food insecurity is associated with numerous adverse
medical and psychosocial outcomes across the lifespan. In this narrative review,
we examine current research on food insecurity, specifically as it relates to
child psychopathology and risk factors thereof: namely, parental mental illness
and poor diet and metabolic health. Moreover, we begin to speculate about
behavioral and physiological mechanisms by which these conditions may influence
one another, and discuss possible interventions through enhanced screening and
treatment, parent training, and provision of high quality foods to vulnerable
households. Further research is needed to the effects of child and parental
mental health on metabolic outcomes in families with food insecurity.
PMID- 27514245
TI - Diet quality, risk factors and access to care among low-income uninsured American
adults in states expanding Medicaid vs. states not expanding under the affordable
care act.
AB - BACKGROUND: The Affordable Care Act (ACA) Medicaid expansion varies in
availability across states. PURPOSE: We compared characteristics of low-income
uninsured residents in both Medicaid nonexpanding and expanding states with
respect to their dietary quality, health risk factors, and access to care.
METHODS: Data from the 2007-2012 National Health and Nutrition Examination Survey
was matched with the Kaiser Family Foundation Medicaid expansion data. Bivariate
and multivariate regressions were estimated to assess differences across
expanding and non-expanding states. RESULT: The non-expansion group had a lower
Healthy Eating Index score (41.8 vs. 44.1, p-value=0.006), a higher Body Mass
Index (29.9 vs. 28.9, p-value=0.032), higher obesity prevalence (41% vs. 33%, p
value=0.007), and lower asthma prevalence (14.8% vs. 19.7%, p-value=0.037)
compared with the expansion group. CONCLUSIONS: Differences across states in
Medicaid coverage under the ACA may lead to widening disparities in health
outcomes between expanding and non-expanding states.
PMID- 27514246
TI - Training fast or slow? Exercise for depression: A randomized controlled trial.
AB - Exercise can be used to treat depression but there is a lack of evidence
regarding the optimal intensity and mode. Our aim was to compare the effects of
different exercise intensities on post-treatment depression severity. People aged
18-67years with mild to moderate depression (Patient Health Questionnaire-9 score
of >=10) participated in a single-blind, parallel randomized control trial
lasting 12-weeks (Sweden 2011-2013). Four treatment arms were included: treatment
as usual (TAU) (n=310), light exercise (yoga or similar n=106), moderate exercise
(aerobic conditioning, n=105) and vigorous exercise (aerobic conditioning, n=99).
Depression severity was measured at baseline and post-treatment using the
Montgomery-Asberg Depression Rating Scale (MADRS). Differences between the groups
in depression severity at post-treatment were analysed using linear regression.
Differences in exercise intensity were confirmed by heart rate monitoring. At
post-treatment, the light (-4.05 Confidence Interval (CI)=-5.94, -2.17), moderate
(-2.08 CI=-3.98, -0.18) and vigorous exercise groups (-3.13 CI=-5.07, -1.19) had
reduced their MADRS scores significantly more than TAU. No significant
differences were found between the exercise groups, and no significant
interaction effect was observed between group and gender. In conclusion,
exercise, whether performed at a low (yoga or similar), moderate or vigorous
intensity (aerobic training) is effective in treating mild to moderate depression
and is at least as effective as treatment as usual by a physician.
PMID- 27514247
TI - Regular family breakfast was associated with children's overweight and parental
education: Results from the ENERGY cross-sectional study.
AB - INTRODUCTION: This study aims to assess (i) the prevalence of having regular
family breakfast, lunch, dinner (i.e. 5-7days/week together with their family)
among 10-12year olds in Europe, (ii) the association between family meals and
child weight status, and (iii) potential differences in having family meals
according to country of residence, gender, ethnicity and parental levels of
education. METHODS: 7716 children (mean age: 11.5+/-0.7years, 52% girls) in eight
European countries (Belgium, Greece, Hungary, The Netherlands, Norway, Slovenia,
Spain, Switzerland) participated in a cross-sectional school-based survey in
2010. Data on family meals were self-reported by the parents and children's
height and weight were objectively measured to determine overweight status.
Binary regression analyses assessed the associations of having regular family
meals (adjusted for potential confounders) with children's overweight/obesity and
to assess potential differences in having family meals according to gender,
ethnicity and parental education, in the total sample and for each country
respectively. RESULTS: The prevalence of regular family meals was 35%, 37% and
76% for breakfast, lunch and dinner respectively. Having regular family
breakfast, but not lunch or dinner, was inversely associated with overweight
(OR=0.78 (95% CI 0.67-0.91)). Children of higher educated parents were more
likely to have regular family breakfast (1.63 (95% CI 1.42-1.86)) and less likely
to have regular family lunch (0.72 (95% CI 0.63-0.82)) compared to children of
lower educated parents. CONCLUSION: This study showed that having regular family
breakfast - but not other family meals- was inversely associated with children's
weight status.
PMID- 27514248
TI - Increasing reach by offering choices: Results from an innovative model for
statewide services for smoking cessation.
AB - Although state quitlines provide free telephone counseling and often include
nicotine replacement therapy (NRT), reach remains limited (1-2% in most states).
More needs to be done to engage all smokers in the quitting process. A possible
strategy is to offer choices of cessation services through quitlines and to
reduce registration barriers. In March 2014, ClearWay MinnesotaSM implemented a
new model for QUITPLAN(r) Services, the state's population-wide cessation
services. Tobacco users could choose the QUITPLAN(r) Helpline or one or more
Individual QUITPLAN(r) Services (NRT starter kit, text messaging, email program,
or quit guide). The program website was redesigned, online enrollment was added,
and a new advertising campaign was created and launched. In 2014-2015, we
evaluated whether these changes increased reach. We also assessed quit attempts,
quit outcomes, predictors of 30-day abstinence, and average cost per quit via a
seven-month follow-up survey. Between March 2014-February 2015, 15,861 unique
tobacco users registered, which was a 169% increase over calendar year 2013. The
majority of participants made a quit attempt (83.7%). Thirty-day point prevalence
abstinence rates (responder rates) were 26.1% for QUITPLAN Services overall,
29.6% for the QUITPLAN Helpline, and 25.5% for Individual QUITPLAN Services.
Several variables predicted quit outcomes, including receiving only one call from
the Helpline and using both the Helpline and the NRT starter kit. Providing
greater choice of cessation services and reducing registration barriers have the
potential to engage more tobacco users, foster more quit attempts, and ultimately
lead to long-term cessation and reductions in prevalence.
PMID- 27514249
TI - Risk factors for late-life depression: A prospective cohort study among older
women.
AB - Depression prevention requires identifying key risk contributors. Prior studies
have identified several factors related to late-life depression but have seldom
addressed factors jointly or in dose-response fashion. This study aimed to
examine a wide range of potential predisposing factors and to estimate individual
and joint contributions to risk of late-life depression in women. A total of
21,728 women aged >=65years, without prior depression, in the Nurses' Health
Study conducted in the United States were followed from 2000 to 2010.
Demographic, social, lifestyle/behavioral and health variables were selected a
priori from the literature or previous findings in this cohort. Depression was
defined as physician/clinician-diagnosed depression, regular antidepressant use,
or the presence of severe depressive symptoms. During 10-year follow-up, 3945
incident cases were identified. After simultaneous multivariable-adjustment,
multiple factors in the domains of social stress (lower self-rated societal
position and high volume of caregiving to disabled/ill relatives), unfavorable
lifestyle (smoking, physical inactivity, heavy or binge drinking), and poor
physical health (multiple comorbidity burden, excessive sleep, difficulty
falling/staying asleep, bodily pain, and physical/functional limitation or
disability) were significantly associated with higher depression risk; many
featured dose-response relationships. Sensitivity analyses that excluded outcomes
within 2years yielded similar estimates. The total population attributable
fraction for all factors was 55.5%. Physical/functional limitation accounted for
one-quarter of population attributable fraction, followed by problematic sleep,
inadequate exercise, and pain (combining for one-third of population attributable
fraction). Efforts to remediate or prevent these factors may contribute to an
efficient strategy for late-life depression prevention in women.
PMID- 27514251
TI - Health-related quality of life of patients on antiretroviral treatment in
Botswana: A cross-sectional study.
AB - OBJECTIVE: Antiretroviral therapy (ART) affords longevity to patients infected
with the human immune deficiency virus (HIV). Since little is known about the
health-related quality of life (HRQoL) of persons who have been on ART for at
least five years, the present study investigated the HRQoL of these patients in
Botswana. METHOD: Medical records, structured interviews, and the World Health
Organization Quality of Life-BREF (WHOQoL-HIV-BREF) instrument were employed to
obtain information from 456 respondents. RESULTS: Univariate and multivariate
regression analyses showed that respondents' highest scores were in the
"physical" domain (mean = 15.8, SD = 3.5), while the lowest scores were in the
"environment" domain (mean = 12.9, SD = 2.5). Thus, the physical domain had the
greatest impact on patients' overall HRQoL. Self-education about HIV-related
issues was significantly correlated with all domains of HRQoL scores: physical
(rho = -2.32, CI 95% = -3.02, -1.61); psychological (rho = -2.26, CI 95% = -2.87,
-1.65); independence (rho = -1.81, CI 95% = -2.54, -1.06); social relationships
(rho = -1.40, CI 95% = -2.13, -0.67); environment (rho = -1.58, CI 95% = -2.13,
1.04); and spirituality (rho = -1.70, CI 95% = -82.27, -1.13). SIGNIFICANCE OF
RESULTS: HRQoL assessments can identify and address patients' needs, and it is
important that guidelines be developed that will yield improved care to ART
patients in Botswana.
PMID- 27514252
TI - Immunotherapeutic strategies for sexually transmitted viral infections: HIV, HSV
and HPV.
AB - More than 1 million sexually transmitted infections (STIs) are acquired each day
globally. Etiotropic drugs cannot effectively control infectious diseases
therefore, there is a dire need to explore alternative strategies especially
those based on the regulation of immune system. The review discusses all rational
approaches to develop better understanding towards immunotherapeutic strategies
based on modulation of immune system in an attempt to curb the elevating risk of
infectious diseases such as HIV, HPV and HSV because of their high prevalence.
Development of monoclonal antibodies, vaccines and several other immune based
treatments are promising alternative strategies that are offering new
opportunities to eradicate pathogens.
PMID- 27514250
TI - A review of the literature on contingency management in the treatment of
substance use disorders, 2009-2014.
AB - This report describes a systematic literature review of voucher and related
monetary-based contingency management (CM) interventions for substance use
disorders (SUDs) over 5.2years (November 2009 through December 2014). Reports
were identified using the search engine PubMed, expert consultations, and
published bibliographies. For inclusion, reports had to (a) involve monetary
based CM; (b) appear in a peer-reviewed journal; (c) include an experimental
comparison condition; (d) describe an original study; (e) assess efficacy using
inferential statistics; (f) use a research design allowing treatment effects to
be attributed to CM. Sixty-nine reports met inclusion criteria and were
categorized into 7 research trends: (1) extending CM to special populations, (2)
parametric studies, (3) extending CM to community clinics, (4) combining CM with
pharmacotherapies, (5) incorporating technology into CM, (6) investigating longer
term outcomes, (7) using CM as a research tool. The vast majority (59/69, 86%) of
studies reported significant (p<0.05) during-treatment effects. Twenty-eight
(28/59, 47%) of those studies included at least one follow-up visit after CM was
discontinued, with eight (8/28, 29%) reporting significant (p<0.05) effects.
Average effect size (Cohen's d) during treatment was 0.62 (95% CI: 0.54, 0.70)
and post-treatment it was 0.26 (95% CI: 0.11, 0.41). Overall, the literature on
voucher-based CM over the past 5years documents sustained growth, high treatment
efficacy, moderate to large effect sizes during treatment that weaken but remain
evident following treatment termination, and breadth across a diverse set of
SUDs, populations, and settings consistent with and extending results from prior
reviews.
PMID- 27514253
TI - [Investigation of indium exposure in workers in indium smelting plant].
AB - OBJECTIVE: To investigate the internal and external exposure levels of indium
(In)in workers in an In smelting plant, and to analyze its distribution
characteristics. METHODS: A survey was performed in 63 employed workers with more
than one year of experience working in an In smelting plant in 2014. The personal
air samples for 31 workers were collected, and the whole blood, serum, and urine
samples of all the 63 workers were collected to do the occupational health
examination at the same time. In levels in all samples were determined by
inductively coupled plasma mass spectrometry. RESULTS: The smelter workers had a
higher In exposure level in the air than the office workers (2.26 MUg/m(3) vs
0.82 MUg/m(3), P>0.05). There was a significant difference in In exposure level
in the air between the workers doing different types of jobs (P<0.05). The In
exposure levels in the air in the metathesis workers and electrolysis workers
were 26.10 MUg/m(3) and 20.99 MUg/m(3), respectively, which were significantly
higher than those in other workers (P<0.05). The smelter workers had
significantly higher geometric means of In levels in the whole blood, serum, and
urine than the office workers (0.44 MUg/L vs 0.09 MUg/L, P<0.05; 0.35 MUg/L vs
0.09 MUg/L, P<0.05; 0.26 MUg/L vs 0.12 MUg/L, P<0.05). There were significant
differences in In levels in the whole blood, serum, and urine between the workers
doing different types of jobs (P<0.05). The metathesis workers (13.0 MUg/L, 4.02
MUg/L, and 2.93 MUg/L)and electrolysis workers (5.71 MUg/L, 5.14 MUg/L, and 4.26
MUg/L)had higher In levels in the whole blood, serum, and urine than other
workers. The In level in the whole blood was positively correlated with the In
levels in the urine and serum (rs=0.601, P<0.05; rs=0.823, P<0.05). The In levels
in the whole blood and urine were positively correlated with the In level in the
air(rs=0.483, P<0.05; rs=0.428, P<0.05). CONCLUSION: In the In smelting plant,
the In concentrations in the air are lower than the standard value, but the
workers have higher In levels in body. The In level in the whole blood is
positively correlated with the In levels in the serum and urine. The In levels in
the whole blood and urine are positively correlated with the In level in the air.
PMID- 27514254
TI - [Effects of job content on psychological stress in young recruits].
AB - OBJECTIVE: To explore the effects of job content on psychological stress in young
recruits. METHODS: In October 2014, 625 young recruits enrolled in one troop of
Xinjiang Military Command in 2014 were chosen as subjects by multi-stage
stratified random sampling. The Chinese version of the job content questionnaire
(JCQ)and the psychological stress self evaluation test (PEST)were used to
investigate the subjects. The subjects were divided into two groups with scores
higher and lower than the mean score of three subscales (job requirement, degree
of autonomy, and social support)of JCQ to explore the effects of job content on
psychological stress in young recruits. The correlation of psychological stress
with three subscales of job content was evaluated using the Pearson' s
correlation analysis. Binary logistic regression analysis was used to analyze the
influencing factors for psychological stress. RESULTS: The PEST score of young
recruits was 49.98+/-9.98. Forty-five (7.68%)out of them had scores of >=70
points and were diagnosed with high levels of psychological stress. When the
subjects were grouped based on socio-demographic characteristics, a high level of
psychological stress was significantly more frequent in subjects less than 20
years of age than in those not less than 20 years of age, in smoking subjects
than in non-smoking subjects, and in urban residents than in rural residents
(10.42% vs 5.03%, P<0.05; 10.14% vs 5.33%, P<0.05; 10.85% vs 5.88% , P <0.05).
There were no significant differences in educational level or identity before
recruitment between subjects with different levels of psychological stress
(P>0.05). In various job content domains that had impacts on psychological
stress, subjects with a low score of social support had significantly higher PEST
scores than those with a high score of social support (50.96+/-10.35 vs 48.49+/
9.22, P<0.01). The PEST score was negatively correlated with the degree of
autonomy and social support (r=-0.103, P<0.05; r=-0.239, P<0.05). The results of
logistic regression analysis showed that job requirement and social support were
influencing factors for psychological stress (OR=0.718, 95% CI= 0.718
(0.607~0.851), P<0.05; OR=1.185, 95% CI=1.185 (1.087~1.292), P<0.05). CONCLUSION:
Psychological stress of young recruits in army is not optimistic. Psychological
stress is weakly negatively correlated with social support. The low scores on job
requirement subscale and social support subscale may be potential protective
factor and risk factor for psychological stress, respectively.
PMID- 27514255
TI - [Changes in levels of human nutritious metabolites after exposure to abnormal
acceleration of sea state].
AB - OBJECTIVE: To investigate the changes in the levels of human blood nutritious
metabolites and its major regulating factors after exposure to abnormal
acceleration of sea state, and to provide clues for further investigating the
mechanism of fatigue due to maritime operations. METHODS: Using randomly sampling
method, 60 healthy male adults from one troop were selected as the subjects on
April 20, 2010. All subjects were exposed to six degrees of freedom motion
simulator ship for 15 min. Their blood samples were collected before and after
exposure to abnormal acceleration immediately. The metabolomic technology was
used to measure the levels of nutritious metabolites in the serum. Enzyme -
linked immunosorbent assay or radioimmunoassay was used to measure the levels of
glucocorticoids, adrenaline, insulin, glucagon, ghrelin, resistin, leptin, and
gastric inhibitory peptide. RESULTS: After exposure to abnormal acceleration, the
subjects showed significant decreases in the levels of serum essential amino
acids, such as L-lysine[(23.63+/-8.24)*10(6) vs(32.83+/-13.58)*10(6), P<0.05], L
methionine[(4.16+/-1.12)*10(6) vs(5.80+/-1.69)*10(6), P<0.05], and L
tryptophan[(29.38+/-8.56)*10(6) vs (35.93+/-11.82)*10(6), P<0.05], and the levels
of some non-essential amino acids, such as L-histidine[(1.69+/-0.55)*10(6)
vs(2.16+/-0.92)*10(6), P<0.05] and 4-hydroxy- L-proline[(3.21+/-1.50)* 10(6) vs
(7.92+/-4.79)*10(6), P<0.05]. After exposure to abnormal acceleration, the
subjects had significant increases in the levels of serum carbohydrate
metabolites, such as glucose[(2412.40+/-700.36)*10(6) vs(1939.30+/-554.33)*10(6),
P< 0.05] and pyruvic acid[(9.97+/-5.96)*10(6) vs(2.43+/-1.34)*10(6), P<0.05], and
the levels of fat metabolites, such as beta-hydroxybutyric acid[(37.47+/
60.21)*10(6) vs(10.29+/-20.64)*10(6), P<0.05], oleic acid[(31.94+/-30.39)*10(6)
vs (15.94+/-10.37)*10(6), P<0.05], and linoleic acid[(26.19+/-19.16)* 10(6) vs
(13.58+/-6.29)* 10(6), P<0.05]. After exposure to abnormal acceleration, the
subjects had significant increases in the levels of serum glucocorticoids
[(743.63+/-129.06)nmol/L vs (539.66+/-155.58)nmol/L, P<0.05],
adrenaline[(725.04+/-367.08)pmol/L vs (482.58+/-194.97)pmol/L, P<0.05],
glucagon[(5.85+/-1.57)pmol/L vs(5.18+/-1.64)pmol/L, P<0.05], and ghrelin[(62.55+/
32.34)pmol/L vs (40.47+/-22.18)pmol/L, P<0.05], and decreases in the levels of
serum insulin[(107.41+/-21.09)pmol/L vs(150.89+/-48.65)pmol/L, P<0.05], gastric
inhibitory peptide[(41.05+/-17.91)pmol/L vs(170.34+/-82.64) pmol/L, P<0.05],
leptin[(25.62+/-21.75)nmol/L vs (46.50+/-27.40)nmol/L, P<0.05], and
resistin[(209.24+/-107.65)nmol/L vs (535.04+/-263.13)nmol/L, P<0.05]. CONCLUSION:
After exposure to abnormal acceleration of sea state, the levels of serum
nutritious metabolites show significant changes and the levels of fatigue
associated products, such as serum pyruvic acid, increase significantly, which
may be related to induced stress response and changes in the levels of metabolic
regulators.
PMID- 27514256
TI - [Association between serum aluminium level and methylation of amyloid precursor
protein gene in workers engaged in aluminium electrolysis].
AB - OBJECTIVE: To investigate the association between serum aluminium level and
methylation of the promoter region of amyloid precursor protein (APP)gene in
workers engaged in aluminium electrolysis. METHODS: In 2012, 366 electrolysis
workers in an aluminium factory were enrolled as exposure group (working years
>10 and age >40 years)and divided into low-exposure group and high-exposure group
based on the median serum aluminium level. Meanwhile, 102 workers in a cement
plant not exposed to aluminium were enrolled as control group. Graphite furnace
atomic absorption spectrometry was used to measure serum aluminium level,
methylation specific PCR was used to measure the methylation rate of the promoter
region of APP gene, and ELI-SA was used to measure the protein expression of APP
in lymphocytes in peripheral blood. RESULTS: The exposure group had a
significantly higher serum aluminium level than the control group (45.07 MUg/L vs
30.51 MUg/L, P< 0.01). The exposure group had a significantly lower methylation
rate of the promoter region of APP gene than the control group (18.85% vs 25.49%,
P=0.025), and the high-exposure group had a significantly lower methylation rate
of the promoter region of APP gene than the low-exposure group (15.84% vs 21.85%,
P<0.05). The exposure group had a significantly higher protein expression of APP
in lymphocytes in peripheral blood than the control group (66.73 ng/ml vs 54.17
ng/ml, P<0.05); compared with the low-exposure group (65.39 ng/ml), the high
exposure group showed an increase in the protein expression of APP in lymphocytes
in peripheral blood (67.22 ng/ml), but there was no significant difference
between these two groups (P>0.05). The multivariate logistic regression analysis
showed that with reference to the control group, low aluminium exposure (OR=1.86,
95% CI 1.67~3.52)and high aluminium exposure (OR=2.98, 95% CI 1.97~4.15)were risk
factors for a reduced methylation rate of the promoter region of APP gene.
CONCLUSION: Reduced methylation of the promoter region of APP gene may be
associated with increased serum aluminium level, and downregulated methylation of
the promoter region of APP gene may accelerate APP gene transcription.
PMID- 27514257
TI - [Metabolic syndrome and its influencing factors in professional automobile
drivers in a company].
AB - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS)in 259
professional automobile drivers, and to put forward targeted suggestions on
protection. METHODS: In October 2014, 114 male bus drivers and 145 male taxi
drivers in a transportation service company were enrolled as investigation group,
and 121 non-operating male staff were enrolled as control group. Physical
examination and a questionnaire survey were conducted for both groups, and the
results were analyzed. RESULTS: The bus drivers and taxi drivers had
significantly higher prevalence rates of MS than the nonoperating
staff(17.5%/13.1% vs 3.3%, P<0.05). The results of univariate logistic analysis
showed that smoking(OR=2.58, 95%CI 1.14~5.88), exercise (OR=0.21, 95% CI
0.10~0.43), meal time (OR=0.27, 95% CI 0.13~0.59), and a family history of
chronic diseases (OR=2.26, 95% CI 1.13~4.50)were associated with MS, and each
independent variable showed significant differences between groups (P<0.05).
Multivariate logistic regression analysis showed that with age remaining the
same, smoking was the risk factor for MS in professional automobile drivers
(OR=5.25, 95%CI 2.00~13.80), and meal time (20~40 min)(OR= 0.20, 95%CI
0.09~0.44)and exercise (OR=0.13, 95% CI 0.06~0.30)were protective factors against
MS. CONCLUSION: Professional automobile drivers have a higher prevalence rate of
MS than non-operating staff, which should be taken seriously by working
personnel.
PMID- 27514258
TI - [Association between psychosocial work environment and workplace bullying among
office workers].
AB - OBJECTIVE: To assess the prevalence of bullying in companies and health care
center and identify the association between psychosocial environment and
workplace bullying. METHODS: A total of 847 employees at in business building
companies and 146 employees at one community health service center were invited
to this survey by cluster sampling during October to December 2014, using
anonymous questionnaires including the general demographic information, job
characteristics, job stress core scale, the social capital scale, and NAQ-R.
RESULTS: The rate of targets of bullying in the two kinds of workplaces were
13.1% and 5.6% respectively. Workplace bullying was associated with employee's
education level(chi(2)=11.17, P=0.019)and the area his or her families live
in(chi(2)=5.66, P=0.017). In addition, workplace bullying was significantly
associated with psychosocial work environment. Job demand was positively
correlated with workplace bullying (OR=2.24, 95% CI=1.34~3.74), and workplace
social support was negatively associated with workplace bullying (OR= 0.33, 95%
CI=0.18~0.60). CONCLUSION: Workplace bullying can be reduced by adjusting certain
working conditions that negatively affect employees who are susceptible to being
bullied, giving their individual and job characteristic. Moreover, workplace
bullying could also be reduced if job demands are limited and job control and
social capital are increased.
PMID- 27514259
TI - [KAP research and intervention effects of health education on prevention and
control of occupational diseases in occupational groups in Jinzhou, China].
AB - OBJECTIVE: To investigate the current status of knowledge, attitude, and practice
(KAP)on the prevention and control of occupational diseases in occupational
groups in Jinzhou, China, and to evaluate the intervention effects of health
education. METHODS: Using the cluster random sampling method, 1000 workers who
underwent occupational health examination in Jinzhou Center for Disease Control
and Prevention from September 2014 to April 2015 were enrolled in this study.
They were equally and randomly divided into intervention group and control group.
The intervention group received health education for 6 months through bulletin
board, promotion materials, expert lecture, Q&A session, and other relevant
educational events. The questionnaire survey was performed before and after
intervention. The control group received the questionnaire survey but not the
health education. RESULTS: The overall awareness rate of prevention and control
knowledge was 75.34% in 990 workers in Jinzhou, China. After the intervention,
the intervention group had a significantly higher awareness rate of prevention
and control knowledge than the control group (89.87%~98.86% vs 71.25%~80.82%,
P<0.05); the intervention group had a significantly higher attitude accuracy for"
whether occupational health examination is necessary or not" and " is willing to
received the training on occupational health knowledge" than the control
group(chi(2)=57.857, P<0.05; chi(2)=70.683, P<0.05); and the intervention group
had a significantly higher rate of correct behavior for" whether help the
business management personnel to carry out the prevention and control of
occupational diseases or not" and"whether actively understand the occupational
hazards of job" (chi(2)=102.186, P<0.05; chi(2)=91.159, P<0.05). CONCLUSION:
Health education can significantly increase the awareness rate of prevention and
control knowledge on occupational diseases in occupational groups in Jinzhou,
China. However, the more structured and longterm comprehensive intervention is
necessary for improving their attitude and behavior.
PMID- 27514260
TI - [Influencing factors for the use of earplugs in workers exposed to noise in a
city].
AB - OBJECTIVE: To investigate the current status of hearing loss and the use of
earplugs in workers exposed to noise who have been provided earplugs in a city,
as well as major influencing factors for the use of earplugs. METHODS: Cluster
random sampling was used to conduct a questionnaire survey in workers exposed to
noise who had been provided earplugs in 15 enterprises with noise exposure in a
city from June to December, 2014. RESULTS: In the workers exposed to noise who
had been provided earplugs, the rate of high-frequency anomaly in both ears was
57.8%, and the workers who kept wearing earplugs only accounted for 55.4%. The
results of binary logistic regression analysis showed that the protective factors
for the use of earplugs included workers' own feeling of hearing condition
(OR=1.704), comfort of earplugs (OR= 1.892), enterprise's inspection of the use
of earplugs (OR=1.461), workers' knowledge of the function and usage of earplugs
(OR=1.581), workers' understanding of the necessity of earplugs (OR=4.482),
workers' initiative to search for related data (OR=4.029), the use of earplugs by
colleagues (OR=5.071), and reminders from family members or friends (OR=2.678)
(all P<0.05). CONCLUSION: The workers exposed to noise in this city have a high
rate of abnormal hearing, and only half of the workers keep wearing earplugs
during work. The use of earplugs is related to the factors including workers' own
feeling of hearing condition, comfort of earplugs, workers' knowledge of
protection, the enterprise' s management of hearing protection, and environmental
support.
PMID- 27514261
TI - [Chromosome aberration and micronucleus frequency in peripheral blood lymphocytes
in radiation workers].
AB - OBJECTIVE: To investigate chromosome aberration and micronucleus frequency in
peripheral blood lymphocytes in workers engaged in radiation for a long time, to
reduce occupational hazard caused by ionizing radiation, and to further
strengthen health surveillance. METHODS: A total of 366 members of medical staff
engaged in radiation work who underwent physical examinations in Hangzhou
Hospital of Prevention and Treatment of Occupation Diseases from 2014 to 2015
were enrolled as radiation group, consisting of staff engaged in X-ray diagnosis,
diagnostic radiology, radiotherapy, and interventional radiology. Another 100
members of medical staff without exposure to radiation were enrolled as control
group. Whole blood culture was used to measure chromosome aberration and
micronucleus frequency in peripheral blood lymphocytes. RESULTS: The radiation
group had a significantly higher rate of chromosome aberration than the control
group (0.30% vs 0.09% , chi(2)= 13.43, P<0.01), as well as a significantly higher
micronucleus frequency than the control group (2.090/00 vs 0.080/00, chi(2)=74.4,
P<0.01). The abnormal rates of chromosome aberration and micronucleus showed no
significant differences across radiation workers with different working years
(P>0.05). The staff engaged in X-ray diagnosis, diagnostic radiology,
radiotherapy, and interventional radiology had rates of chromosome aberration of
0.25%, 0.25%, 0.23%, and 0.41%, respectively, which showed a significant
difference between the staff at these four posts (chi(2)=8.22, P<0.05); the
micronucleus frequencies in the staff at these four posts were 1.360/00,
1.280/00, 1.140/00, and 3.790/00, respectively, and showed a significant
difference between the staff at these four posts (chi(2)=251.09, P<0.01).
CONCLUSION: Radiation workers are exposed to lowdose ionizing radiation for a
long time, which may cause significant increases in the rate of chromosome
aberration and micronucleus frequency in peripheral blood lymphocytes.
PMID- 27514262
TI - [Field investigation of occupational disease diagnosis in Guangdong Provincial
Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014: an
analysis of 136 cases].
AB - OBJECTIVE: To investigate the characteristics of 136 patients with occupational
diseases, to summarize key techniques used in field investigation, and to provide
a scientific basis for the development of standard operating procedures for field
investigation of occupational disease diagnosis. METHODS: Field investigation and
routine data analysis were performed to analyze the cases diagnosed by Guangdong
Provincial Hospital for Occupational Disease Prevention and Treatment from
January 2009 to December 2014. RESULTS: A total of 136 cases of occupational
diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease
Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia,
18 cases of suspected occupational benzene poisoning, 12 cases of suspected
occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis.
Of all these patients, 41.91% were engaged in at least three types of work,
70.59% were exposed to at least three types of chemicals, 25.74% experienced
changes in technical processes and chemicals, and 47.06% had disputes on the
chemicals they were exposed to during verification by both parties. Occupational
hazard factors were detected. Most samples (358)were used to measure benzene
concentration in workplace air, among which 11.7% had a benzene concentration of
>6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of
3.26~6.00 mg/m(3), 75.42% had a benzene concentration of<0.03 to <3.25 mg/m(3).
The samples of suspected occupational hand-arm vibration disease, suspected
pneumoconiosis, and suspected occupational noiseinduced hearing loss had high
overstandard rates (100%, 93.8%, and 83.3%, respectively). CONCLUSION: Field
investigation of occupational disease diagnosis reveals large numbers of cases of
leukemia, suspected occupational benzene poisoning, suspected occupational hand
arm vibration disease, and suspected pneumoconiosis. The key aspects of field
investigation include confirmation of the history of occupational exposure,
identification of occupational hazard factors, confirmation of the changes in
technical processes and chemicals, detection of occupational hazard factors,
sampling and analysis of raw materials, and epidemiological investigation of
workers with the same type of work.
PMID- 27514263
TI - [The current situation of physical activity of basic level civil servants in
Anhui province].
PMID- 27514264
TI - [Aluminuminduced impairment in primary cultured rat choroid plexus epithelial
cells].
AB - OBJECTIVE: To investigate the impairment in primary cultured rat choroid plexus
epithelial cells (CPECs)induced by aluminum. METHODS: The choroid plexus isolated
from Sprague-Dawley rats 14 days old was cut into pieces and digested by trypsin
in the sterile area. The obtained single cells were cultured in DMEM with 1%
epidermal growth factor and 20% fetal calf serum. Five days later,
immunohistochemistry with anti-transthyretin antibody was used to identify the
purity of cultured cells. The well-grown cells were treated with aluminum lactate
at different concentrations (0, 100, 400, and 1 600 MUmol/L for control, lowdose,
mediumdose, and highdose groups). Fortyeight hours later, the cell viability,
apoptotic rate, level of reactive oxygen species (ROS), and activity of
superoxide dismutase (SOD)were measured in each group to evaluate the impairment
in primary cultured rat CPECs by aluminum. RESULTS: More than 95% of the cultured
cells were identified as CPECs. The medium-and high-dose groups had significantly
lower cell viability than the control group(86.74%+/-4.03% vs 100%, P<0.01;
81.90%+/-9.17% vs 100%, P<0.01). The high-dose group had significantly lower cell
viability than the lowdose group (81.90%+/-9.17% vs 92.92%+/-8.81%, P<0.01). The
medium-and high-dose groups had significantly higher apoptotic rates than the
control group (7.26%+/-0.99% vs 1.29%+/-0.03%, P<0.01; 22.25%+/-1.55% vs 1.29%+/
0.03%, P<0.01)and the low-dose group (7.26%+/-0.99% vs 1.68%+/-0.27%, P<0.01;
22.25%+/-1.55% vs 1.68%+/-0.27%, P<0.01). The high-dose group had a significantly
higher apoptotic rate than the medium-dose group (22.25%+/-1.55% vs 7.26%+/
0.99%, P<0.01). The mediumand high-dose groups had significantly higher
fluorescence intensity of ROS than the control group (22.23%+/-0.41% vs 17.24%+/
0.09%, P<0.05; 25.10%+/-1.13% vs 17.24%+/-0.09%, P<0.05)and the lowdose group
(22.23%+/-0.41% vs 18.31%+/-0.21%, P<0.05; 25.10%+/-1.13% vs 18.31%+/-0.21%,
P<0.05). The highdose group had significantly higher fluorescence intensity of
ROS than the mediumdose group (25.10%+/-1.13% vs 22.23%+/-0.41%, P< 0.05). The
low-, medium-and high-dose groups had significantly lower SOD activity than the
control group[(28.65+/-0.74)U/g Hb vs (37.35+/-1.05)U/g Hb, P<0.05; (22.75+/
1.94)U/g Hb vs (37.35+/-1.05)U/g Hb, P<0.05; (13.29+/-0.64)U/g Hb vs(37.35+/
1.05)U/g Hb, P<0.05]. The medium-and high-dose groups had significantly lower SOD
activity than the low-dose group[(22.75+/-1.94)U/g Hb vs(28.65+/-0.74)U/g Hb,
P<0.05; (13.29+/-0.64)U/g Hb vs (28.65+/-0.74)U/g Hb, P<0.05], while the high
dose group had had significantly lower SOD activity than the medium-dose
group[(13.29+/-0.64)U/g Hb vs (22.75+/-1.94)U/g Hb, P<0.05]. There were no
significant differences in cell viability, apoptotic rate, level of ROS, or
activity of SOD between any other two groups (P>0.05). CONCLUSION: Aluminum
lactate may induce impairment in primary cultured rat CPECs. It reduces the cell
viability, elevates the apoptotic rate, and causes oxidative stress.
PMID- 27514265
TI - [Occupational asthma: an analysis of two cases].
AB - OBJECTIVE: To investigate the incidence of occupational asthma induced by
occupational exposure to detergents and spices. METHODS: The occupational
history, case data, and results of auxiliary examinations were collected from
patients with asthma induced by occupational exposure to detergents and spices
and submitted to the expert group for diagnosis of occupational diseases to
obtain the diagnostic results. RESULTS: Both patients with asthma were exposed to
asthmogenic substances in the working environment and developed the symptoms of
asthma after a certain latency period. In case 1, the patient had positive
results from bronchial dilation test and peak expiratory flow test; in case 2,
the patient had positive results from allergen skin prick test for spices and
essence and allergen bronchial provocation test. Therefore, the possibility of
asthma induced by occupational factors could not be excluded. CONCLUSION:
Occupational exposure to detergents and spices can induce occupational asthma.
PMID- 27514266
TI - [Pulmonary siderosis: a case report and thought for the diagnosis].
PMID- 27514267
TI - [Peripheral nerve injury induced by occupational expsure to 1bromopropane in 4
cases].
PMID- 27514268
TI - [Treatment of a case of ataxia and pyramidal tract sign positive contact with the
organic solvent].
PMID- 27514269
TI - [Determination of thiodiglycolic acid in urine by ion chromatography with
solidphase extraction].
AB - OBJECTIVE: To establish a SPE-IC method to determine the thiodiglycolic acid in
the urine of workers who were exposed to vinyl chloride monomer. METHODS: The
samples were prepared by the process of being centrifuged and purified by C18 SPE
column before separated by AS19 anion exchange column and detected by
conductivity detector. The thiodiglycolic acid were characterized by the
retention time and quantified by peak area and external standard method. RESULTS:
The range of linearity was 0.05~50.00 MUg/ml, and the correlation coefficient was
0.999 9. The method detection limit was 0.1 MUg/ml and the method quantitative
limit was 0.3 MUg/ml. The within-run precision was 1.26%~5.03% and the betweenrun
precision was 0.50%~8.78%. The spiked recoveries were 80.10%~104.20%. Samples
could bestored at-20 C for at least 2 weeks. The determination of thiodiglycolic
acid could not be interfered by chloroacetic acid, dichloroacetic acid,
trichloroacetic acid and other endogenous ionic compounds. CONCLUSION: This
method is feasible for determination of thiodiglycolic acid in the urine of
workers who were exposed to vinyl chloride monomer.
PMID- 27514270
TI - [Determination of bromoform in the air of workplace by solvent desorption gas
chromatography].
AB - OBJECTIVE: To establish the method of solvent desorption gas chromatography for
determination of bromoform in workplace air. METHODS: Bromoform in the air was
adsorbed by activated carbon tube sampling and solvent desorption using carbon
disulfide, then analyed by GC with DB-FFAP capillary column. RESULTS: The linear
regression equation is y=1.22x-0.81 (r=0.999 9)between 0.57~300.00 MUg/ml of
target concentration in the air. The detection limit was 0.17 MUg /ml. The
relative standard deviations of the batch and inter batch were 1.7%~3.6%,
2.8%~6.3%, respectively. The sampling efficiency was 100%. The overall desorption
efficiency was 95.0%. The breakthrough capacity was more than 0.61 mg(100 mg
activated carbon). CONCLUSION: The method is suitable to determine bromoform in
the air of workplace.
PMID- 27514271
TI - [Graphite furnace atomic absorption spectrometry for determination of thallium in
blood].
AB - OBJECTIVE: Colloidal palladium was used as chemical modifier in the determination
of blood thallium by graphite furnace atomic absorption spectrometry. METHODS:
Blood samples were precipitated with 5% (V/V)nitric acid, and then determined by
GFAAS with colloidal palladium used as a chemical modifier. 0.2% (W/V)sodium
chloride was added in the standard series to improve the matrix matching between
standard solution and sample. RESULTS: The detection limit was 0.2 MUg/L. The
correlation coefficient was 0.9991. The recoveries were between 93.9% to
101.5%.The relative standard deviations were between 1.8% to 2.7%.The certified
reference material of whole blood thallium was determined and the result was
within the reference range Conclusion: The method is accurate, simple and
sensitive, and it can meet the needs of detection thallium in blood entirely.
PMID- 27514272
TI - [Determination of hippuric acid and methylhippuric acid in urine by high
performance liquid chromatography after extracted with acetonitrile].
AB - OBJECTIVE: To establish pretreatment conditions of hippuric acid (HA)and methyl
hippuric acid (MHA)in urine and HPLC conditions. METHODS: HA and MHA in urine
were extracted with acetonitrile under acid condition and determinated by HPLC
DAD. The operating conditions by HPLC were C18 column (150 mm* 4.6 mm, 5 MUm),
methanol-0.2% acetic acid (contained 6.5 mmol/L potassium dihydrogen
phosphate)(25?75, V/V) as mobile phase,1 ml/min as flow rate and wavelength was
at 254 nm. RESULTS: The standard curves for HA, 2-MHA and 3-MHA(4-MHA)showed good
linearity between 9.91~2 974.20 MUg/ml(r=0.999 98), 1.91~573.60 MUg/ml (r=0.999
84)and 2.00~598.65 MUg/ml (r=0.999 85), respectively. The mean recoveries were
96.38%~98.01%, 83.17%~94.05 %, 103.22%~104.45%, respectively. The within-run
precision were 0.50%~1.20%, 0.51%~1.59%, 0.49%~0.95%, respectively, and the
between-run precision were 1.70%~3.20%, 1.30%~2.67%, 0.86%~2.74%, respectively.
The detection limit of HA, 2-MHA and 3-MHA(4-MHA)were 0.18 MUg/ml, 0.46 MUg/ml
and 0.12 MUg/ml, and the low determination concentrations of the method were 0.36
MUg/ml, 0.92 MUg/ml and 0.24 MUg/ml(1 ml urine). The urine can be kept 15 days at
4 C refrigerator without significantly loss. CONCLUSION: This method with simply
pretreatment conforms to the relevant requirements of guide for establishing
occupational health standards-part 5: determination methods of chemicals in
biological materials. It can be used to detect HA and MHA in urine for
occupational population exposure to toluene and xylene.
PMID- 27514273
TI - [Exploration on the problems in the process of the development of occupatieral
disease prevention and control planning].
PMID- 27514274
TI - [Analysis for the systemof regulations and standards of occupational safety and
health in British].
PMID- 27514275
TI - [The evolution of physical agents standards based on hygienic standards for the
design of industrial enterprises].
PMID- 27514276
TI - [Research progress on the influence of occupational stress on industrial injury
accident].
PMID- 27514277
TI - Co-immobilization of Palm and DNase I for the development of an effective anti
infective coating for catheter surfaces.
AB - Biomaterial-associated infections, in particular, catheter-associated infections
(CAI) are a major problem in clinical practice due to their ability to resist
antimicrobial treatment and the host immune system. This study aimed to co
immobilize the antimicrobial lipopeptide Palm and the enzyme DNase I to introduce
both antimicrobial and anti-adhesive functionalities to polydimethylsiloxane
(PDMS) material, using dopamine chemistry. Surface characterization confirmed the
immobilization of both compounds and no leaching of Palm from the surfaces for up
to 5days. Co-immobilization of both agents resulted in a bifunctional coating
with excellent surface antimicrobial and anti-biofilm properties against both
Staphylococcus aureus and Pseudomonas aeruginosa. The modified surfaces
demonstrated superior biocompatibility. To better discriminate co-adhesion of
both species on modified surfaces, PNA FISH (Fluorescence in situ hybridization
using peptide nucleic acid probes) was employed, and results showed that P.
aeruginosa was the dominant organism, with S. aureus adhering afterwards on P.
aeruginosa agglomerates. Furthermore, Palm immobilization exhibited no propensity
to develop bacterial resistance, as opposite to the immobilization of an
antibiotic. The overall results highlighted that co-immobilization of Palm and
DNase I holds great potential to be applied in the development of catheters.
STATEMENT OF SIGNIFICANCE: Catheter-associated infections (CAI) are the most
common hospital-acquired infections worldwide. Several coating strategies have
been proposed to fight these infections but most of them present some important
limitations, including the emergence of resistant bacteria and toxicity concerns.
The present work describes a two-step polydopamine-based surface modification
strategy to successfully co-immobilize an antimicrobial peptide (Palm) and an
enzyme targeting an important component of biofilm matrix (DNase I). This
immobilization approach imparted polydimethylsiloxane surfaces with both anti
adhesive and antimicrobial properties against the adhesion of relevant bacteria
as single and dual-species, with excellent stability and biocompatible and anti
biofilm properties, holding, therefore, great potential in the development of
catheters able to prevent CAI.
PMID- 27514278
TI - FES-induced co-activation of antagonist muscles for upper limb control and
disturbance rejection.
AB - Control systems for human movement based on Functional Electrical Stimulation
(FES) have shown to provide excellent performance in different experimental
setups. Nevertheless, there is still a limited number of such applications
available today on worldwide markets, indicating poor performance in real
settings, particularly for upper limb rehabilitation and assistance. Based on
these premises, in this paper we explore the use of an alternative control
strategy based on co-activation of antagonist muscles using FES. Although co
contraction may accelerate fatigue when compared to single-muscle activation,
knowledge from motor control indicate it may be useful for some applications. We
have performed a simulation and experimental study designed to evaluate whether
controllers that integrate such features can modulate joint impedance and, by
doing so, improving performance with respect to disturbance rejection. The
simulation results, obtained using a novel model including proprioceptive
feedback and anatomical data, indicate that both stiffness and damping components
of joint impedance may be modulated by using FES-induced co-activation of
antagonist muscles. Preliminary experimental trials were conducted on four
healthy subjects using surface electrodes. While the simulation investigation
predicted a maximum 494% increase in joint stiffness for wrist flexion/extension,
experiments provided an average elbow stiffness increase of 138% using lower
stimulation intensity. Closed-loop experiments in which disturbances were applied
have demonstrated that improved behavior may be obtained, but increased joint
stiffness and other issues related to simultaneous stimulation of antagonist
muscles may indeed produce greater errors.
PMID- 27514279
TI - Hydrodynamic dispensing and electrical manipulation of attolitre droplets.
AB - Dispensing and manipulation of small droplets is important in bioassays, chemical
analysis and patterning of functional inks. So far, dispensing of small droplets
has been achieved by squeezing the liquid out of a small orifice similar in size
to the droplets. Here we report that instead of squeezing the liquid out, small
droplets can also be dispensed advantageously from large orifices by draining the
liquid out of a drop suspended from a nozzle. The droplet volume is adjustable
from attolitre to microlitre. More importantly, the method can handle suspensions
and liquids with viscosities as high as thousands mPa s markedly increasing the
range of applicable liquids for controlled dispensing. Furthermore, the movement
of the dispensed droplets is controllable by the direction and the strength of an
electric field potentially allowing the use of the droplet for extracting
analytes from small sample volume or placing a droplet onto a pre-patterned
surface.
PMID- 27514280
TI - Stereoselective synthesis of vinylsilanes via copper-catalyzed silylation of
alkenes with silanes.
AB - An efficient and stereoselective synthesis of vinylsilanes via copper-catalyzed
direct silylation of alkenes with silanes was developed. This study offers a new
and expedient strategy for the synthesis of synthetically useful alkenyl
organosilicon compounds in satisfactory yields and may provide a low-cost and
environmentally benign alternative to currently employed precious metal systems
for alkene silylation. Moreover, the transformation is proposed to proceed via a
radical process and exhibits a broad substrate scope and good functional group
tolerance.
PMID- 27514281
TI - Dissociable effects of the prodrug phendimetrazine and its metabolite
phenmetrazine at dopamine transporters.
AB - Phendimetrazine (PDM) is a clinically available anorectic and a candidate
pharmacotherapy for cocaine addiction. PDM has been hypothesized to function as a
prodrug that requires metabolism to the amphetamine-like monoamine transporter
substrate phenmetrazine (PM) to produce its pharmacological effects; however,
whether PDM functions as an inactive prodrug or has pharmacological activity on
its own remains unclear. The study aim was to determine PDM pharmacological
mechanisms using electrophysiological, neurochemical, and behavioral procedures.
PDM blocked the endogenous basal hDAT (human dopamine transporter) current in
voltage-clamped (-60 mV) oocytes consistent with a DAT inhibitor profile, whereas
its metabolite PM induced an inward hDAT current consistent with a DAT substrate
profile. PDM also attenuated the PM-induced inward current during co-application,
providing further evidence that PDM functions as a DAT inhibitor. PDM increased
nucleus accumbens dopamine levels and facilitated electrical brain stimulation
reinforcement within 10 min in rats, providing in vivo evidence supporting PDM
pharmacological activity. These results demonstrate that PDM functions as a DAT
inhibitor that may also interact with the pharmacological effects of its
metabolite PM. Overall, these results suggest a novel mechanism for PDM
therapeutic effects via initial PDM DAT inhibition followed by PM DAT substrate
induced dopamine release.
PMID- 27514283
TI - Sample Dimensionality Effects on d' and Proportion of Correct Responses in
Discrimination Testing.
AB - Products in the food and beverage industry have varying levels of dimensionality
ranging from pure water to multicomponent food products, which can modify sensory
perception and possibly influence discrimination testing results. The objectives
of the study were to determine the impact of (1) sample dimensionality and (2)
complex formulation changes on the d' and proportion of correct response of the 3
AFC and triangle methods. Two experiments were conducted using 47 prescreened
subjects who performed either triangle or 3-AFC test procedures. In Experiment I,
subjects performed 3-AFC and triangle tests using model solutions with different
levels of dimensionality. Samples increased in dimensionality from 1-dimensional
sucrose in water solution to 3-dimensional sucrose, citric acid, and flavor in
water solution. In Experiment II, subjects performed 3-AFC and triangle tests
using 3-dimensional solutions. Sample pairs differed in all 3 dimensions
simultaneously to represent complex formulation changes. Two forms of complexity
were compared: dilution, where all dimensions decreased in the same ratio, and
compensation, where a dimension was increased to compensate for a reduction in
another. The proportion of correct responses decreased for both methods when the
dimensionality was increased from 1- to 2-dimensional samples. No reduction in
correct responses was observed from 2- to 3-dimensional samples. No significant
differences in d' were demonstrated between the 2 methods when samples with
complex formulation changes were tested. Results reveal an impact on proportion
of correct responses due to sample dimensionality and should be explored further
using a wide range of sample formulations.
PMID- 27514282
TI - Somatic KCNJ5 mutation occurring early in adrenal development may cause a novel
form of juvenile primary aldosteronism.
AB - We report a case of non-familial juvenile primary aldosteronism (PA). Super
selective adrenal venous sampling identified less aldosterone production in the
right inferior adrenal segment than others. Bilateral adrenalectomy sparing the
segment normalized blood pressure and improved PA. Both adrenals had similar
histologies, consisting of a normal adrenal cortex and aldosterone synthase
positive hyperplasia/adenoma. An aldosterone-driving KCNJ5 mutation was detected
in the lesions, but not in the histologically normal cortex. After taking into
account that the two adrenal glands displayed a similar histological profile, as
well as the fact that hyperplastic lesions in both glands exhibited a common
KCNJ5 mutation, we conclude that the specific mutation may have occurred at an
adrenal precursor mesodermal cell, at an early stage of development; its daughter
cells were mixed with non-mutant cells and dispersed into both adrenal glands,
resulting into a form of the condition known as genetic mosaicism.
PMID- 27514284
TI - 19 F NMR transverse and longitudinal relaxation filter experiments for screening:
a theoretical and experimental analysis.
AB - Ligand-based 19 F NMR screening represents an efficient approach for performing
binding assays. The high sensitivity of the methodology to receptor binding
allows the detection of weak affinity ligands. The observable NMR parameters that
are typically used are the 19 F transverse relaxation rate and isotropic chemical
shift. However, there are few cases where the 19 F longitudinal relaxation rate
should also be used. A theoretical and experimental analysis of the 19 F NMR
transverse and longitudinal relaxation rates at different magnetic fields is
presented along with proposed methods for improving the sensitivity and dynamic
range of these experiments applied to fragment-based screening. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27514285
TI - Spectral and kinetic effects accompanying the assembly of core complexes of
Rhodobacter sphaeroides.
AB - In the present work, spectral and kinetic changes accompanying the assembly of
the light-harvesting 1 (LH1) complex with the reaction center (RC) complex into
monomeric RC-LH1 and dimeric RC-LH1-PufX core complexes of the photosynthetic
purple bacterium Rhodobacter sphaeroides are systematically studied over the
temperature range of 4.5-300K. The samples were interrogated with a combination
of optical absorption, hole burning, fluorescence excitation, steady state and
picosecond time resolved fluorescence spectroscopy. Fair additivity of the LH1
and RC absorption spectra suggests rather weak electronic coupling between them.
A low-energy tail revealed at cryogenic temperatures in the absorption spectra of
both monomeric and dimeric core complexes is proved to be due to the special pair
of the RC. At selected excitation intensity and temperature, the fluorescence
decay time of core complexes is shown to be a function of multiple factors, most
importantly of the presence/absence of RCs, the supramolecular architecture
(monomeric or dimeric) of the complexes, and whether the complexes were studied
in a native membrane environment or in a detergent - purified state.
PMID- 27514286
TI - Epilepsy: Noninvasive detection of deep brain seizures.
PMID- 27514289
TI - Trial watch: Phase III trial of anti-tau drug generates mixed messages.
PMID- 27514288
TI - Epilepsy: A dietary supplement for SUDEP prevention?
PMID- 27514290
TI - In the news: AAIC 2016 lights up Toronto.
PMID- 27514287
TI - Myeloid cells - targets of medication in multiple sclerosis.
AB - Discussions of multiple sclerosis (MS) pathophysiology tend to focus on T cells
and B cells of the adaptive immune response. The innate immune system is less
commonly considered in this context, although dendritic cells, monocytes,
macrophages and microglia - collectively referred to as myeloid cells - have
prominent roles in MS pathogenesis. These populations of myeloid cells function
as antigen-presenting cells and effector cells in neuroinflammation. Furthermore,
a vicious cycle of interactions between T cells and myeloid cells exacerbates
pathology. Several disease-modifying therapies are now available to treat MS, and
insights into their mechanisms of action have largely focused on the adaptive
immune system, but these therapies also have important effects on myeloid cells.
In this Review, we discuss the evidence for the roles of myeloid cells in MS and
the experimental autoimmune encephalomyelitis model of MS, and consider how
interactions between myeloid cells and T cells and/or B cells promote MS
pathology. Finally, we discuss the direct and indirect effects of existing MS
medications on myeloid cells.
PMID- 27514291
TI - Supportive and symptomatic management of amyotrophic lateral sclerosis.
AB - The main aims in the care of individuals with amyotrophic lateral sclerosis (ALS)
are to minimize morbidity and maximize quality of life. Although no cure exists
for ALS, supportive and symptomatic care provided by a specialist
multidisciplinary team can improve survival. The basis for supportive management
is shifting from expert consensus guidelines towards an evidence-based approach,
which encourages the use of effective treatments and could reduce the risk of
harm caused by ineffective or unsafe interventions. For example, respiratory
support using noninvasive ventilation has been demonstrated to improve survival
and quality of life, whereas evidence supporting other respiratory interventions
is insufficient. Increasing evidence implicates a causal role for metabolic
dysfunction in ALS, suggesting that optimizing nutrition could improve quality of
life and survival. The high incidence of cognitive dysfunction and its impact on
prognosis is increasingly recognized, although evidence for effective treatments
is lacking. A variety of strategies are used to manage the other physical and
psychological symptoms, the majority of which have yet to be thoroughly
evaluated. The need for specialist palliative care throughout the disease is
increasingly recognized. This Review describes the current approaches to
symptomatic and supportive care in ALS and outlines the current guidance and
evidence for these strategies.
PMID- 27514292
TI - Pre-eclampsia and risk of infantile haemangioma.
AB - BACKGROUND: Infantile haemangioma is the most common tumour of infancy, but the
association with pre-eclampsia is poorly understood. OBJECTIVES: We determined
the relationship between variants of pre-eclampsia and risk of infantile
haemangioma. METHODS: We carried out a retrospective cohort study of hospital
data for all live births between 1989 and 2013 in Quebec, Canada. We identified
14 240 neonates with, and 1 930 564 without haemangioma before discharge, and
determined whether early- or late-onset pre-eclampsia was documented on the
maternal chart. We used log-binomial regression to compute prevalence ratios
(PRs) and 95% confidence intervals (CIs) for the association between pre
eclampsia and infantile haemangioma, adjusted for maternal characteristics.
RESULTS: The prevalence of any haemangioma was higher for pre-eclampsia than for
no pre-eclampsia (81.3 vs. 72.9 per 10 000), with a PR of 1.15 (95% CI 1.06-1.25)
after adjustment for maternal characteristics. Pre-eclampsia with onset before 34
weeks' gestation was associated with cutaneous (PR 2.32, 95% CI 1.68-3.21),
noncutaneous (PR 3.66, 95% CI 2.49-5.37) and unspecified haemangioma (PR 2.49,
95% CI 1.77-3.49). However, the association between early-onset pre-eclampsia and
haemangioma was attenuated once long neonatal length of hospital stays was
accounted for. There was no association with late-onset pre-eclampsia after 34
weeks, and associations were weaker for other variants including severe pre
eclampsia and pre-eclampsia with low birthweight. CONCLUSIONS: Early-onset pre
eclampsia is associated with increased risk of haemangioma at birth, but
detection bias due to longer hospital stays and closer follow-up may be part of
the reason.
PMID- 27514294
TI - Adverse Effects of Psychotropic Medications: A Call to Action.
AB - Adverse effects are common, bothersome, and a leading cause of discontinuation of
treatment. The methodology for evaluating adverse effects of medications has been
greatly neglected, however, especially in comparison to the methodology for
assessment of efficacy of medications. Existing methods for assessment and
reporting of adverse effects have important limitations leading to lack of much
needed data related to adverse effects. Lastly, there is little systematic
research into management of most adverse effects. A series of recommendations are
made in this article about how to improve identification, assessment, reporting,
and management of adverse effects.
PMID- 27514293
TI - Degree connectivity in body dysmorphic disorder and relationships with obsessive
and compulsive symptoms.
AB - Individuals with body dysmorphic disorder (BDD) and obsessive-compulsive disorder
(OCD) are categorized within the same major diagnostic group and both show
regional brain hyperactivity in the orbitofrontal cortex (OFC) and the basal
ganglia during symptom provocation. While recent studies revealed that degree
connectivity of these areas is abnormally high in OCD and positively correlates
with symptom severity, no study has investigated degree connectivity in BDD. We
used functional magnetic resonance imaging (fMRI) to compare the local and
distant degree of functional connectivity in all brain areas between 28
unmedicated BDD participants and 28 demographically matched healthy controls
during a face-processing task. Correlational analyses tested for associations
between degree connectivity and symptom severity assessed by the BDD version of
the Yale-Brown obsessive-compulsive scale (BDD-Y-BOCS). Reduced local amygdalar
connectivity was found in participants with BDD. No differences in distant
connectivity were found. BDD-Y-BOCS scores significantly correlated with the
local connectivity of the posterior-lateral OFC, and distant connectivity of the
posterior-lateral and post-central OFC, respectively. These findings represent
preliminary evidence that individuals with BDD exhibit brain-behavioral
associations related to obsessive thoughts and compulsive behaviors that are
highly similar to correlations previously found in OCD, further underscoring
their related pathophysiology. This relationship could be further elucidated
through investigation of resting-state functional connectivity in BDD, ideally in
direct comparison with OCD and other obsessive-compulsive and related disorders.
PMID- 27514295
TI - Core Concepts Involving Adverse Psychotropic Drug Effects: Assessment,
Implications, and Management.
AB - Adverse effects from psychiatric drugs can profoundly influence treatment
adherence and outcomes. Good care involves addressing adverse effects no
differently than any other component of treatment. Knowledge about adverse effect
assessment and management fosters a proper context that helps clinicians not
sacrifice a drug's potential therapeutic benefits because of greater concerns
about its tolerability. This article provides an overview of basic concepts
related to the assessment and management of suspected adverse effects from
psychotropic drugs. Key points are discussed regarding clinical, pharmacogenetic,
pharmacokinetic, and pharmacodynamic risk factors for treatment-emergent adverse
effects, alongside recommendations for their systematic assessment.
PMID- 27514296
TI - Drug-Induced Extrapyramidal Syndromes: Implications for Contemporary Practice.
AB - The development of drugs to treat psychosis is a fascinating nexus for
understanding mechanisms underlying disorders of mind and movement. Although the
risk of drug-induced extrapyramidal syndromes has been mitigated by the
acceptance of less potent dopamine antagonists, expansive marketing and off-label
use has increased the number of susceptible people who may be at risk for these
neurologic effects. Clinicians need to be familiar with advances in diagnosis and
management, which are reviewed herein. A better understanding of drug-induced
effects on the motor circuit may improve patient safety, enhance antipsychotic
effectiveness, and provide insights into mechanisms underlying antipsychotic
activity in parallel brain circuits.
PMID- 27514297
TI - Serotonin Reuptake Inhibitors and Risk of Abnormal Bleeding.
AB - Serotonin reuptake inhibitors (SRIs) increase the risk of abnormal bleeding by
lowering platelet serotonin and hence the efficiency of platelet-driven
hemostasis; by increasing gastric acidity and possibly gastric ulceration; and by
other mechanisms. The upper gastrointestinal tract is the commonest site of SRI
related abnormal bleeding; bleeding at this location may be increased by
concurrent nonsteroidal anti-inflammatory drug therapy and by treatment with
antiplatelet or anticoagulant drugs. Bleeding at this location may be reduced by
concurrent administration of acid-suppressing drugs.
PMID- 27514298
TI - Sexual Dysfunction Due to Psychotropic Medications.
AB - Sexual functioning is important to assess in patients with psychiatric illness as
both the condition and associated treatment may contribute to sexual dysfunction
(SD). Antidepressant medications, mood stabilizers, antipsychotics, and
antianxiety agents may be associated with SD related to drug mechanism of action.
Sexual adverse effects may be related to genetic risk factors, impact on
neurotransmitters and hormones, and psychological elements. Effective strategies
to manage medication-induced sexual dysfunction are initial choice of a drug
unlikely to cause SD, switching to a different medication, and adding an antidote
to reverse SD. Appropriate interventions should be determined on a clinical case
by-case basis.
PMID- 27514299
TI - Adverse Effects in the Pharmacologic Management of Bipolar Disorder During
Pregnancy.
AB - Management of bipolar disorder during pregnancy often involves medications with
potential adverse effects, including risks to the mother and fetus. Although some
specifics are known, many medications continue to have incompletely characterized
reproductive safety profiles. Women with bipolar disorder who are planning
pregnancy face challenging decisions about their treatment; careful risk-benefit
discussions are necessary. With the goal of further informing these discussions,
this article reviews the data currently available regarding medication safety in
the management of bipolar disorder during pregnancy, with specific attention to
lithium, valproic acid, lamotrigine, carbamazepine, and antipsychotic
medications.
PMID- 27514300
TI - Adverse Effects of Second-Generation Antipsychotics as Adjuncts to
Antidepressants: Are the Risks Worth the Benefits?
AB - Over the past decades, several adjunctive therapies have been introduced for
treatment-resistant depression (TRD), and these strategies have ebbed and flowed
in popularity. Currently, adjunctive therapy with the second-generation
antipsychotics (SGAs) is most commonly used by psychiatrists. Four SGAs are FDA
approved for indications related to TRD (aripiprazole, brexpiprazole, olanzapine,
and quetiapine extended release); some evidence also supports use of risperidone
and ziprasidone as adjunctive therapies. This article briefly reviews the role of
adjunctive therapy with SGAs in contemporary algorithms for TRD, considering both
the evidence of benefit and the adverse effects.
PMID- 27514301
TI - Adverse Effects of Psychotropic Medications on Sleep.
AB - Psychotropic medications such as antidepressants, antipsychotics, stimulants, and
benzodiazepines are widely prescribed. Most of these medications are thought to
exert their effects through modulation of various monoamines as well as
interactions with receptors such as histamine and muscarinic cholinergic
receptors. Through these interactions, psychotropics can also have a significant
impact on sleep physiology, resulting in both beneficial and adverse effects on
sleep.
PMID- 27514302
TI - Antidepressants and Suicidality.
AB - We review the evidence that antidepressants either increase or decrease the risk
for suicidal ideation and behavior in adolescents. Meta-analyses of randomized
clinical trials (RCTs) indicate a small increased risk for suicidal events in
adolescents and young adults, but a protective effect in older adults. In
contrast, pharmacoepidemiologic studies show a protective effect across the life
span. Explanations for occurrence of suicidal events in younger patients and for
the apparent contradiction between RCT and pharmacoepidemiologic studies are
offered. Guidance for clinicians is provided on explaining the risk-benefit ratio
of antidepressants and how to monitor and attenuate for suicidal risk.
PMID- 27514303
TI - Adverse Effects of Electroconvulsive Therapy.
AB - Electroconvulsive therapy (ECT) is an effective treatment commonly used for
depression and other major psychiatric disorders. We discuss potential adverse
effects (AEs) associated with ECT and strategies for their prevention and
management. Common acute AEs include headache, nausea, myalgia, and confusion;
these are self-limiting and are managed symptomatically. Serious but uncommon AEs
include cardiovascular, pulmonary, and cerebrovascular events; these may be
minimized with screening for risk factors and by physiologic monitoring. Although
most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may
rarely persist. Modifications of and improvements in treatment techniques
minimize cognitive and other AEs.
PMID- 27514304
TI - The Neglected Side of Suffering.
PMID- 27514305
TI - Vein of Galen aneurysmal malformation (VGAM) in the fetus: retrospective analysis
of perinatal prognostic indicators in a two-center series of 49 cases.
AB - OBJECTIVE: Vein of Galen aneurysmal malformation (VGAM) is a rare fetal anomaly,
the neurological outcome of which can be good with appropriate perinatal
management. However, most fetal series are too small to allow reliable
statistical assessment of potential prognostic indicators. Our aim was to assess,
in a two-center series of 49 cases, the prognostic value of several prenatal
variables, in order to identify possible prenatal indicators of poor outcome, in
terms of mortality and cerebral disability. METHODS: This was a retrospective
study involving 49 cases of VGAM diagnosed prenatally and managed at two centers
over a 17-year period (1999-2015). All cases had undergone detailed prenatal
cerebral and cardiac assessment by grayscale ultrasound, color and pulsed-wave
Doppler and magnetic resonance imaging (MRI). Ultrasound and MRI examination
reports and images were reviewed and outcome information was obtained from
medical reports. Volume of the VGAM (on ultrasound and MRI) was calculated and
development of straight-sinus dilatation, ventriculomegaly and other major brain
abnormalities was noted. Cardiothoracic ratio, tricuspid regurgitation and
reversed blood flow across the aortic isthmus were evaluated on fetal
echocardiography. Major brain lesions were considered by definition to be
associated with poor outcome in all cases. Pregnancy and fetoneonatal outcome
were known in all cases. Fetoneonatal outcome and brain damage were considered as
dependent variables in the statistical evaluation. Poor outcome was defined as
death, late termination of pregnancy due to association with related severe brain
anomalies or severe neurological impairment. RESULTS: At a mean follow-up time of
20 (range, 0-72) months, 36.7% of the whole series and 52.9% of the cases which
did not undergo late termination were alive and free of adverse sequelae. Five
(10.2%) cases showed progression of the lesion between diagnosis and delivery. On
univariate analysis, dilatation of the straight sinus, VGAM volume >= 20 000 mm3
and tricuspid regurgitation were all significantly related to poor outcome.
However, on logistic regression analysis, the only variables associated
significantly with poor outcome were tricuspid regurgitation and, to a lesser
extent, VGAM volume >= 20 000 mm3 . The former was also the only variable
associated with brain damage. CONCLUSIONS: Major brain lesions, tricuspid
regurgitation and, to a lesser extent, VGAM volume >= 20 000 mm3 are the only
prenatal variables associated with poor outcome in fetal VGAM. Prenatal
multidisciplinary counseling should be based on these variables. Copyright (c)
2016 ISUOG. Published by John Wiley & Sons Ltd.
PMID- 27514306
TI - Transformation of atenolol, metoprolol, and carbamazepine in soils: The
identification, quantification, and stability of the transformation products and
further implications for the environment.
AB - Pharmaceuticals are a large group of substances that have been recognized as
environmental contaminants in recent years. Research on the pharmaceutical fate
in soils is currently limited or missing. In this study, three pharmaceuticals
(atenolol (ATE), carbamazepine (CAR), and metoprolol (MET)) were introduced to
soils and exposed for 61 day under aerobic conditions. Thirteen different soils
were used in the study to increase the understanding of pharmaceutical behaviour
in the soil matrix. Ten metabolites were detected and tentatively identified.
Some of them, such as atenolol acid (AAC), carbamazepine 10,11-epoxide (EPC),
10,11-dihydrocarbamazepine (DHC), trans-10,11-Dihydro-10,11-dihydroxy
carbamazepine (RTC), and metoprolol acid (MAC), were consequently confirmed using
commercial reference standards. It was concluded that the aerobic conditions of
the experiment determined the pharmaceutical degradation pathway of studied
compounds in the soils. The different amounts/rates and degradation of the
transformation products can be attributed to differences in the soil properties.
ATE degraded relatively quickly compared with CAR, whereas MET degradation in the
soils was unclear. The persistence of CAR and its metabolites, in combination
with low CAR sorption, enable the transportation of CAR and its metabolites
within soils and into the ground water. Thus, CAR may cause adverse effects on
the environment and humans.
PMID- 27514307
TI - Coherent control of light-matter interactions in polarization standing waves.
AB - We experimentally demonstrate that standing waves formed by two coherent counter
propagating light waves can take a variety of forms, offering new approaches to
the interrogation and control of polarization-sensitive light-matter interactions
in ultrathin (subwavelength thickness) media. In contrast to familiar energy
standing waves, polarization standing waves have constant electric and magnetic
energy densities and a periodically varying polarization state along the wave
axis. counterintuitively, anisotropic ultrathin (meta)materials can be made
sensitive or insensitive to such polarization variations by adjusting their
azimuthal angle.
PMID- 27514309
TI - The efficacy of video monitoring-supported student self-evaluation of dental
explorer skills in dental hygiene education.
AB - OBJECTIVE: The objective of this study was to investigate whether having dental
hygiene students monitor video recordings of their dental explorer skills is an
effective means of proper self-evaluation in dental hygiene education. METHODS:
The study participants comprised students of a dental hygiene training school who
had completed a module on explorer skills using models, and a dental hygiene
instructor who was in charge of lessons. Questions regarding 'posture', 'grip',
'finger rest' and 'operation' were set to evaluate explorer skills. Participants
rated each item on a two-point scale: 'competent (1)' or 'not competent (0)'. The
total score was calculated for each evaluation item in evaluations by students
with and without video monitoring, and in evaluations by the instructor with
video monitoring. Mean scores for students with and without video monitoring were
compared using a t-test, while intraclass correlation coefficients were found by
reliability analysis of student and instructor evaluations. RESULTS: A total of
37 students and one instructor were subject to analysis. The mean score for
evaluations with and without video monitoring differed significantly for posture
(P < 0.0001), finger rest (P = 0.0006) and operation (P < 0.0001). The intraclass
correlation coefficient between students and instructors for evaluations with
video monitoring ranged from 0.90 to 0.97 for the four evaluation items.
CONCLUSION: The results of this study suggested that having students monitor
video recordings of their own explorer skills may be an effective means of proper
self-evaluation in specialized basic education using models.
PMID- 27514310
TI - Clinical assessment of rosacea severity: oriental score vs. quantitative
assessment method with imaging and biomedical tools.
AB - BACKGROUND: Rosacea is a common chronic inflammatory disorder affecting facial
skin. Currently, no accurate and objective method is available for assessing the
severity of rosacea. Most studies use the National Rosacea Society Standard
(NRSS) grading method, which lacks objectivity and yields varying results.
METHODS: Eighteen patients with rosacea were included. Clinical severity was
assessed on the basis of the NRSS grade, Investigators' Global Assessment,
Patients' Global Assessment, and Dermatology Quality of Life Index. A skin color
analysis system was used to measure the facial area showing erythema, and
biophysical parameters of facial skin (transepidermal water loss and skin surface
hydration) were examined. To find statistical significant in classification
severity of the rosacea, statistical analysis was performed with all parameters.
RESULTS: A significant correlation (P < 0.05) was found between the NRSS grade,
facial area showing erythema, and biophysical parameters. The latter two factors
differed significantly among patients with rosacea of different levels of
severity (mild, moderate, severe; P < 0.05). CONCLUSION: Color imaging systems
can be useful and reliable for evaluating the severity of rosacea, in addition to
biophysical parameter assessment. The combination of these two analytical methods
enabled objective and quantitative evaluation of the severity of rosacea.
PMID- 27514308
TI - Morphine decreases the pro-angiogenic interaction between breast cancer cells and
macrophages in vitro.
AB - Interactions between the various cell types that constitute a solid tumour are
essential to the biology of the tumour. We evaluated the effect of morphine on
the proangiogenic interaction taking place between macrophages and breast cancer
cells in vitro. The conditioned medium (CM) from breast cancer cells co-cultured
with macrophages elicited endothelial cell proliferation and tube formation. This
effect was inhibited if the co-culture occurred in the presence of morphine. The
CM from breast cancer cells or macrophages grown individually, whether or not
prepared in the presence of morphine, was ineffective in stimulating EC
proliferation or tube formation. Using a mouse antibody array, we identified
several angiogenesis-regulating factors differentially expressed in the CM of co
cultured cells prepared in the presence or absence of morphine, amongst which
interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and vascular endothelial
growth factor (VEGF)-A. VEGF was induced in both cell types by the co-culture and
this was prevented by morphine in a non-naloxone reversible fashion. The effect
of CM from co-cultured cells on endothelial tube formation, but not
proliferation, was prevented by anti-VEGF neutralizing antibody. Our results
indicate that morphine prevents, in part via modulating VEGF-A expression, the
pro-angiogenic interaction between macrophages and breast cancer cells.
PMID- 27514311
TI - Comparative study of different histologic classifications in the degree of
differentiation in endometrial adenocarcinoma.
AB - PURPOSE: To evaluate the concordance among the available histologic
classifications for endometrial adenocarcinoma using interobserver and
intraobserver agreement as well as the association of tumor histologic degree in
the above mentioned classifications with cellular proliferation measured by Ki
67. METHODS: Seventy women who underwent surgical treatment of endometrial
adenocarcinoma with histologic confirmation of endometrioid type were included in
the study. Two experienced pathologists randomly analyzed the slides in 3
distinct timeframes with a maximum of 25 slides/timeframe. Tumor slides were
classified according to the degree of differentiation using 4 different
classifications: International Federation of Gynecology and Obstetrics (FIGO),
modified FIGO, Lax, and Alkushi. RESULTS: Intraobserver agreement was reasonable
for classification of FIGO (k 0.469 and 0.538), very good for modified FIGO (k
0.661 and 0.768), moderate for Lax classification (k 0.496 and 0.466), and
moderate/good for Alkushi classification (k 0.528 and 0.736). Interobserver
concordance was regular for FIGO classification (k = 0.271 and 0.343),
good/moderate for modified FIGO classification (k = 0.661 and 0.522,
respectively), regular/moderate for Lax classification (k = 0.258 and 0.465,
respectively), and regular for Alkushi classification (k = 0.283 and 0.402).
CONCLUSIONS: The prognostic value of histologic grading in endometrial carcinoma
and its importance for a successful therapeutic plan have been documented
repeatedly, but the best grading system, in terms of prognostication,
reproducibility, ease of use, and universality (e.g., applicability to all tumor
cell types), has not been unequivocally defined.
PMID- 27514312
TI - Variation in hospital utilization at the end of life for patients with cancer in
the Emilia-Romagna region of Italy.
AB - INTRODUCTION: Despite the preference of many patients to die at home, high
proportions of patients with advanced cancer undergo major procedures, receive
intensive care, and die in the hospital. The goal of this study is to examine
variation in hospital utilization and site of death for patients dying with poor
prognosis cancer in the Regione Emilia-Romagna (RER), Italy. METHODS: We
conducted a retrospective, population-level study using administrative data.
Patients were included if they died in 2012 and had at least one hospital
admission for metastatic or poor-prognosis cancer within 180 days of death.
Variations in the use of the hospital, intensive care, and procedures performed
were evaluated. RESULTS: 11,470 patients died with metastatic or poor-prognosis
cancer in 2012. Seventy-eight percent of patients were hospitalized in the last
month of life while 50.7% of patients died in the hospital. Results varied by
local health authority from 38.3% to 69.3%. Of patients who had an ICU stay,
55.1% in the community hospitals and 59.8% in the teaching hospitals were
admitted to the ICU on the day of death or the day before death. 7.5% of patients
underwent a major procedure in the last 30 days of life. CONCLUSIONS: The overall
high rate, and substantial variation, in hospital care at the end of life offers
the RER the opportunity to evaluate if increasing availability of palliative
care, along with provider and patient education, could reduce utilization of high
cost hospital care and increase patient and family satisfaction.
PMID- 27514313
TI - Analysis of clinical and pathological characteristics, treatment methods,
survival, and prognosis of uterine papillary serous carcinoma.
AB - PURPOSE: Uterine papillary serous carcinoma (UPSC) is an atypical variant of
endometrial carcinoma with a poor prognosis. It is commonly associated with an
increased risk of extrauterine disease. The aim of this study was to investigate
clinical and pathological characteristics, therapeutic methods, and prognostic
factors in women with UPSC. METHODS: All patients who underwent surgery for UPSC
at a single high-volume cancer center between January 1995 and December 2010 were
retrospectively reviewed. Patients who did not undergo surgical staging and those
with mixed tumor histology were excluded. Univariate and multivariate regression
models were used to identify the risk factors for overall survival (OS) and
progression-free survival (PFS). RESULTS: A total of 46 patients were included,
the majority of whom having stage I disease (IA, 13 [28.2%] and IB, 12 [26.7%]).
Stages II, III, and IV were identified in 5 (10.9%), 8 (17.4%), and 8 (17.4%)
women, respectively. Optimal cytoreduction was obtained in 67.3% of patients.
Recurrences developed in 8 (17.4%) patients. Multivariate analysis confirmed that
lymphovascular space invasion (LVSI) (odds ratio [OR] 26.83, p = 0.003) was the
only independent prognostic factor for OS, whereas LVSI and optimal cytoreduction
were found to be independent prognostic factors for PFS (OR 6.91, p = 0.013 and
OR 2.69, p = 0.037, respectively). The 5-year overall survival rate was 63%.
CONCLUSIONS: Our study demonstrated that LVSI is the only independent prognostic
factor for OS, whereas LVSI and optimal cytoreduction are independent prognostic
factors for PFS in patients with UPSC.
PMID- 27514314
TI - Rationale and protocol of AIRC IG-13218, short-term radiotherapy for early
prostate cancer with concomitant boost to the dominant lesion.
AB - INTRODUCTION: Of the different treatments for early prostate cancer,
hypofractionated external-beam radiotherapy is one of the most interesting and
studied options. METHODS: The main objective of this phase II clinical study is
to evaluate the feasibility, in terms of the incidence of acute side effects, of
a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer
patients treated with the latest imaging and radiotherapy technology, allowing
dose escalation to the dominant intraprostatic lesion identified by
multiparametric magnetic resonance imaging. Secondary endpoints of the study are
the evaluation of the long-term tolerability of the treatment in terms of late
side effects, quality of life, and efficacy (oncological outcome). RESULTS: The
study is ongoing, and we expect to complete recruitment by the end of 2016.
CONCLUSIONS: Like in previous studies, we expect ultra-hypofractionated radiation
treatment for prostate cancer to be well tolerated and effective. TRIAL
REGISTRATION: ClinicalTrials.gov identifier: NCT01913717.
PMID- 27514315
TI - Factors related to treatment outcomes in low-risk gestational neoplasia.
AB - OBJECTIVE: To define the factors associated with methotrexate (MTX) resistance in
patients with low-risk gestational trophoblastic neoplasia (GTN). METHODS: A
total of 63 patients with low-risk GTN according to International Federation of
Gynecology and Obstetrics (FIGO) criteria were included. A total of 37 (58.7%)
patients were treated with successive doses of 1 mg/kg intramuscular (IM) MTX on
days 1, 3, 5, and 7, and 0.1 mg/kg IM folinic acid (FA) on days 2, 4, 6, and 8,
until beta-human chorionic gonadotropin (hCG) levels were normalized. After the
beta-hCG value dropped to the normal level, an additional cycle of MTX/FA was
administered. This protocol is defined as the standard protocol. In a watchful
waiting protocol, the same 8-day IM MTX/FA regimen was given only once (n = 8) or
twice (n = 18) to 26 (41.3%) patients and patients in whom beta-hCG values
declined were subjected to follow-up and no additional cycles were administered
as long as there was a decrease in beta-hCG value. Clinical response and factors
affecting therapeutic outcomes were analyzed retrospectively. RESULTS: Of 63
patients, 47 (74.3%) were cured with primary MTX/FA treatment irrespective of any
protocol. Of the 16 patients who were not able to be treated with primary MTX/FA,
3 were treated with single-agent actinomycin-D and 11 were treated with multi
agent chemotherapy. Univariate analysis showed that a pretreatment beta-hCG level
of >=5000 IU/L was related to reduced therapeutic response (p = 0.001). The FIGO
score, antecedent gestational pathology, and treatment with standard or watchful
waiting protocol were not related to treatment response. CONCLUSIONS: The level
of beta-hCG prior to therapy is an important factor for predicting therapeutic
outcomes. It should be noted that the success of the therapy decreases notably in
case of high beta-hCG level.
PMID- 27514316
TI - Combined modality therapy for thoracic and head and neck cancers: a review of
updated literature based on a consensus meeting.
AB - PURPOSE: Combined modality therapy is a mainstay option for thoracic malignancies
and head and neck cancers. The integration of different strategies is based on
the multidisciplinary approach of modern clinical oncology. Radiation oncologists
have to be educated, trained, and updated to provide state-of-the-art care to
cancer patients and thus educational meetings are crucial. METHODS: The Italian
Association of Radiation Oncology Young Members Working Group (AIRO Giovani)
organized its 8th national meeting, focused on combination therapy in lung,
esophageal, and head and neck cancer (with a specific focus on larynx
preservation strategies for larynx/hypopharynx tumors), involving young
professionals working in Italy. The meeting was addressed to young radiation
oncologists, presenting state-of-the-art knowledge, based on the latest evidence
in this field. We performed a review of the current literature based on the
highlights of the Congress. RESULTS: The multimodality approach of head and neck
and thoracic malignancies includes surgery, chemotherapy, and radiotherapy, but
also has to take into account new information and data coming from basic and
translational research and including molecular biology, genetics, and immunology.
All these aspects are crucial for the treatment of non-small-cell lung cancer and
esophageal, esophagogastric junction, and larynx/hypopharynx malignancies. The
integration of different treatments in the clinical decision-making process to
combine therapies is crucial. CONCLUSIONS: Combination therapy has proved to be a
consolidated approach in these specific oncologic settings, highlighting the
importance of multimodality management in modern clinical oncology. Dedicated
meetings on specific topics are helpful to improve knowledge and skills of young
professionals in radiation oncology.
PMID- 27514317
TI - Experience with belatacept rescue therapy in kidney transplant recipients.
AB - In kidney transplant recipients with chronic graft dysfunction, long-term
immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi)
can be challenging due to adverse effects, such as nephrotoxicity and
proteinuria. Seventy-nine kidney transplant recipients treated with CNI-based or
mTORi-based maintenance immunosuppression who had CNI-induced nephrotoxicity or
severe adverse events were switched to belatacept. Mean time from transplantation
to belatacept conversion was 69.0 months. Mean estimated glomerular filtration
rate (eGFR) +/- standard deviation at baseline was 26.1 +/- 15.0 ml/min/1.73 m2 ,
increasing to 34.0 +/- 15.2 ml/min/1.73 m2 at 12 months postconversion (P <
0.0005). Renal function improvements were also seen in patients with low eGFR
(<25 ml/min/1.73 m2 ) or high proteinuria (>500 mg/l) at conversion. The Kaplan
Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%,
respectively. The discontinuation rate due to adverse events was 7.9%. One case
of post-transplant lymphoproliferative disorder occurred at 17 months
postconversion. For comparison, a historical control group of 41 patients
converted to mTORi-based immunosuppression because of biopsy-confirmed CNI
induced toxicity was examined; eGFR increased from 27.6 +/- 7.2 ml/min/1.73 m2 at
baseline to 31.1 +/- 11.9 ml/min/1.73 m2 at 12 months (P = 0.018). Belatacept
based immunosuppression may be an alternative regimen for kidney transplant
recipients with CNI- or mTORi-induced toxicity.
PMID- 27514318
TI - Tip in-light on: Advantages, challenges, and applications of combining AFM and
Raman microscopy on biological samples.
AB - Scanning probe microscopies and spectroscopies, especially AFM and Confocal Raman
microscopy are powerful tools to characterize biological materials. They are both
non-destructive methods and reveal mechanical and chemical properties on the
micro and nano-scale. In the last years the interest for increasing the lateral
resolution of optical and spectral images has driven the development of new
technologies that overcome the diffraction limit of light. The combination of AFM
and Raman reaches resolutions of about 50-150 nm in near-field Raman and 1.7-50
nm in tip enhanced Raman spectroscopy (TERS) and both give a molecular
information of the sample and the topography of the scanned surface. In this
review, the mentioned approaches are introduced, the main advantages and problems
for application on biological samples discussed and some examples for successful
experiments given. Finally the potential of colocated AFM and Raman measurements
is shown on a case study of cellulose-lignin films: the topography structures
revealed by AFM can be related to a certain chemistry by the colocated Raman scan
and additionally the mechanical properties be revealed by using the digital
pulsed force mode. Microsc. Res. Tech. 80:30-40, 2017. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27514320
TI - Influence of Polymer Electronics on Selective Dispersion of Single-Walled Carbon
Nanotubes.
AB - The separation and isolation of semiconducting and metallic single-walled carbon
nanotubes (SWNTs) on a large scale remains a barrier to many commercial
applications. Selective extraction of semiconducting SWNTs by wrapping and
dispersion with conjugated polymers has been demonstrated to be effective, but
the structural parameters of conjugated polymers that dictate selectivity are
poorly understood. Here, we report nanotube dispersions with a poly(fluorene-co
pyridine) copolymer and its cationic methylated derivative, and show that
electron-deficient conjugated pi-systems bias the dispersion selectivity toward
metallic SWNTs. Differentiation of semiconducting and metallic SWNT populations
was carried out by a combination of UV/Vis-NIR absorption spectroscopy, Raman
spectroscopy, fluorescence spectroscopy, and electrical conductivity
measurements. These results provide new insight into the rational design of
conjugated polymers for the selective dispersion of metallic SWNTs.
PMID- 27514319
TI - Comparison of a vascular closure device versus the radial approach to reduce
access site complications in non-ST-segment elevation acute coronary syndrome
patients: The angio-seal versus the radial approach in acute coronary syndrome
trial.
AB - OBJECTIVES: To compare the radial versus femoral approach using Angio-Seal for
the incidence of access site complications among non-ST-segment elevation acute
coronary syndrome patients undergoing invasive strategy. BACKGROUND: Arterial
access is a major site of complications after invasive coronary procedures.
Vascular closure devices provide more comfort to patients decreasing time to
hemostasis and need for bed rest. However, the inconsistency of data proving
their safety limits their routine adoption as a strategy to prevent vascular
complications. METHODS: Single-center non-inferiority trial where 240 patients
were randomized to radial or femoral access using Angio-Seal. The primary
objective was the occurrence of complications at the arterial puncture site until
30 days after the procedure. RESULTS: There were no baseline clinical differences
between groups, except for a greater prevalence of female patients in the radial
group (33.3 vs. 20.0%, P = 0.020). Hemostasis was achieved in the entire radial
group with the use of TR Band and in 95% of the procedures in the femoral group
with Angio-Seal (P = 0.029). Except for a higher incidence of asymptomatic
arterial occlusion in the radial group, there were no differences among the other
analyzed outcomes. According to the noninferiority test, the use of Angio-Seal
was noninferior to the radial approach, considering the margin of 15% (12.5 vs.
13.3%, difference -0.83%, 95% CI -9.31 - 7.65, P for noninferiority <0.001).
CONCLUSIONS: Angio-Seal seems noninferior in the incidence of access site
complications at 30 days when compared with the radial approach. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27514321
TI - Supramolecular Interactions Direct the Formation of Two Structural Polymorphs
from One Building Unit in a One-Pot Synthesis.
AB - Two polymorphs of supramolecular isomers, a discrete dimer and a zig-zag chain,
having the same chemical composition, [Mn(Hbit)Cl2 ] (Hbit=1-methyl-2-(1H-1,2,3
triazol-4-yl)-1H-benzo[d]imidazole), were obtained solvothermally in a one-pot
synthesis. The isomers differ in a number of ways: orange blocks versus pale
yellow needles, triclinic P1? versus orthorhombic Pbcn, double MU2 -Cl versus
alternate single and triple MU2 -Cl, coordination number 5 versus 6, and
antiparallel versus parallel near-neighbor orientation of Hbit. The packing in
each case is driven by the supramolecular interactions, H-bonds (N-H???Cl, C
H???Cl) and pi???pi overlaps, calculated to be in the range 20-36 kcal mol-1 .
Calculations gave a difference of only 2 kcal mol-1 in favor of the dimer, which
confirms with the observation of principally the dimer at short reaction time.
ESI-MS spectra of the dissolved crystals reveal the same fragments with similar
distributions. The presence of two fragments at m/z 286.96 [MnIV (Hbit)Cl-2H]+
and 323.94 [MnIII (Hbit)Cl2 ]+ indicates that [Mn(Hbit)Cl2 ] is the building unit
in both cases; thus, the different orientations of the ligands lead to the two
polymorphs stabilized by the respective supramolecular interactions. Importantly,
the chain form represents the first example with alternate single and triple MU2
Cl bridges. The magnetic interactions are weakly antiferromagnetic in both cases,
with J in the range 0.07-0.34 cm-1 ; however, high-field EPR analysis reveals
moderate magneto-anisotropy with D=0.26(1) cm-1 , E=0.06(1) cm-1 and D=0.17(1) cm
1 , E=0.03(1) cm-1 , respectively.
PMID- 27514322
TI - Outcome of living donor liver transplantation using right liver allografts with
multiple arterial supply.
AB - A right liver graft with multiple hepatic artery (HA) stumps can be found in
approximately 5% of living donor liver transplantation (LDLT) using a right lobe
graft. From January 2000 to June 2014, 1149 patients underwent LDLT procedures.
Thirty patients with LDLT using a right lobe graft with multiple HA stumps and
149 patients with LDLT using a right lobe graft with a single HA stump were
enrolled. These patients were divided into 3 groups: single HA (group 1, n =
149), multiple HAs with total reconstruction (group 2, n = 19), and multiple HAs
with selective partial reconstruction (group 3, n = 11). Selective partial
reconstruction was performed only when pulsatile back-bleeding was confirmed
after larger HA reconstruction and sufficient intrahepatic arterial flow was
confirmed by Doppler ultrasound (DUS). In group 2, the donor HAs were smaller (P
< .001), and HA reconstruction took longer (P < .001). However, there was no
significant difference among the groups regarding the arterial complication rate,
biliary complication rate, and patient and graft survival. In conclusion,
selective partial reconstruction of HA stumps for LDLT using a right lobe graft
was feasible when intrahepatic arterial communication was confirmed by pulsatile
back-bleeding from the smaller artery and DUS. Liver Transplantation 22 1649-1655
2016 AASLD.
PMID- 27514324
TI - Read all about it.
PMID- 27514323
TI - Magnetic molecularly imprinted polymers for the determination of beta-agonist
residues in milk by ultra high performance liquid chromatography with tandem mass
spectrometry.
AB - A simple, accurate, and highly sensitive analytical method was developed in this
study for the determination of nine beta-agonists in milk. In this method, a new
magnetic adsorbent of molecularly imprinted polymers/magnetic nanoparticles
prepared by simple physical blending was adopted, which enabled magnetic solid
phase extraction. Thus, the resultant material can be separated from the solvent
rapidly and conveniently by a magnet. Two kinds of molecularly imprinted
polymer/magnetic nanoparticles materials were fabricated, and the characteristics
of materials such as the ratio, pH, amount, desorption, and regeneration were
investigated. The analytes were quantified by ultra high performance liquid
chromatography coupled to an electrospray ionization tandem mass spectrometer
operating in multiple reaction monitoring modes. The detection limit of the
method was 0.003-0.3 MUg/L, and the detection capability was 0.01-0.3 MUg/L. The
recoveries of these compounds were 65.7-114% at three spiked levels.
Reproducibility represented by relative standard deviation was 11.2% or less. The
method was successfully applied to the screening of real samples obtained from
local markets and confirmation of the suspected target analytes.
PMID- 27514325
TI - Oral health: An evidence-based approach.
PMID- 27514326
TI - Managing drug addicts.
PMID- 27514327
TI - Depression and dental outcomes.
PMID- 27514328
TI - Antimicrobial resistance: COMs and OMFSs.
PMID- 27514334
TI - What does the future hold for orthodontics?
PMID- 27514331
TI - Course report: Intravenous conscious sedation training for the whole team.
PMID- 27514336
TI - Edwin Russell Bishop.
PMID- 27514337
TI - Rosalind (Ros) C. Randall.
PMID- 27514338
TI - Making time for what's important: what elements should we value when planning
practice-based professional training?
AB - Newly qualified professional healthcare graduates, whether training to become
doctors, dentists, veterinary surgeons or nurses, tend to need some support as
they take their first steps along that bumpy road from university to confident,
competent practice. We identify some key features of the UK programme of dental
practice-based training to acknowledge its strengths - 12 months of clinical
practice within a well-established dental team, one-to-one weekly meetings with
the same dedicated mentor, regular peer learning with the same group of peers
over 12 months and the opportunity to observe role models from the profession
including training programme directors and other general dental practitioners
(GDPs). This educational programme is unique to dentistry and this article
outlines why we believe it is important to value these features when designing
postgraduate professional training in healthcare sciences.
PMID- 27514339
TI - A change in the NICE guidelines on antibiotic prophylaxis.
AB - Since 2008, NICE clinical guidelines have stated: 'Antibiotic prophylaxis against
infective endocarditis is not recommended for people undergoing dental
procedures'. This put UK guidance at odds with guidance in the rest of the world,
where antibiotic prophylaxis is recommended for patients at high-risk of
infective endocarditis undergoing invasive dental procedures. Many dentists also
felt this wording prohibited the use of antibiotic prophylaxis, regardless of the
wishes of the patient or their personal risk of infective endocarditis and made
it difficult for them to use their clinical judgment to deliver individualised
care in the best interests of their patients. NICE have now changed this guidance
to 'Antibiotic prophylaxis against infective endocarditis is not recommended
routinely for people undergoing dental procedures.' This article examines the
implications of this small but important change.
PMID- 27514340
TI - A personal perspective and update on erosive tooth wear - 10 years on: Part 1 -
Diagnosis and prevention.
AB - Tooth wear has been recognised as an increasing problem over the past 10 years.
Recent data from epidemiological studies indicate that the condition is common
with prevalence of dentine exposure in adults ranging between 2% and 10% and
visible surface changes on teeth observed up to 30% of European adults. The Basic
Erosive Wear Examination (BEWE) was designed for general practitioners to score
the severity using similar protocols as the Basic Periodontal Examination (BPE).
The role of the BEWE is partly to increase awareness, but also a means to record
the severity in the clinical notes. Over the past 10 years toothpaste
manufacturers have launched products to prevent progression of erosive tooth wear
using specially formulated fluorides or calcium based products. Probably the most
important preventive advice is to reduce the frequency of acidic foods and
drinks, particularly outside meal times.
PMID- 27514341
TI - Reconnecting the mouth to the body.
AB - The relationship between patient-reported general health and lifestyle factors
and oral health outcomes.
PMID- 27514342
TI - Is the provision of sedation fair?
AB - Conscious sedation: is this provision equitable? Analysis of sedation services
provided within primary dental care in England, 2012-2014.
PMID- 27514343
TI - Energy or taste: why are teenagers drinking sports drinks?
AB - A survey of sports drinks consumption among adolescents.
PMID- 27514344
TI - 'Social anonymity': The ethics of facial transplantation.
AB - '...unlikely to make people 'beautiful'; rather '[i]t will make them look normal
and forgettable - that is its virtue'.
PMID- 27514345
TI - Botulinum toxin - neuropathic pain: Safety and efficacy of repeated injections of
botulinum toxin A in peripheral neuropathic pain (BOTNEP): a randomised, double
blind, placebo-controlled trial.
AB - When treated with botulinum toxin A, those patients with peripheral neuropathic
pain and allodynia (triggering of pain from stimuli which do not normally provoke
pain) at baseline, would appear to have a better outcome.
PMID- 27514346
TI - Botulinum toxin - intraorally: Intraoral administration of botulinum toxin for
trigeminal neuropathic pain.
AB - Intraoral administration was used in addition to the conventional extraoral
administration of botulinum toxin.
PMID- 27514350
TI - Corrigendum.
PMID- 27514360
TI - Erratum.
PMID- 27514349
TI - Orthodontics in antiquity: myth or reality.
AB - Malocclusion, although a common finding in today's world, appears to have been
less frequent in antiquity. There are references to overcrowding, delayed
exfoliation of deciduous teeth and basic orthodontic treatment in the writings of
classical authors such as Hippocrates, Celsus and Galen. However, early authentic
archaeological finds of dental appliances are extremely rare. Considerable
attention has focussed on gold banded devices excavated from ancient Etruscan
sites in central Italy which have been dated to around the seventh to the fourth
centuries BC, with a number of authors suggesting an orthodontic function for
these appliances. This paper reviews the evidence for the possible treatment of
malocclusions in antiquity and concludes that the use of orthodontic appliances
to facilitate tooth movement is not supported by the available evidence.
PMID- 27514348
TI - An assessment of student experiences and learning based on a novel undergraduate
e-learning resource.
AB - Purpose/objectives The aims of this study were to describe the development of a
novel e-learning resource and to assess its impact on student learning
experiences and orthodontic knowledge.Methods Thirty-two 4th year dental
undergraduate students at Queen Mary University of London were randomly allocated
to receive electronic access to e-learning material covering various
undergraduate orthodontic topics over a 6-week period. Thirty-one control
students were not given access during the study period. All students were asked
to complete electronic quizzes both before (T0) and after (T1) the study period
and a general questionnaire concerning familiarity with e-learning. The test
group also completed a user satisfaction questionnaire at T1. Two focus groups
were also undertaken to explore learners' experiences and suggestions in relation
to the resource.Results The mean quiz result improved by 3.9% and 4.5% in the
control and test groups, respectively. An independent t-test, however,
demonstrated a lack of statistical significance in knowledge gain between control
and test groups (P = 0.941). The qualitative feedback indicated that students
believed that use of the resource enhanced knowledge and basic understanding with
students expressing a wish to ingrain similar resources in other areas of
undergraduate teaching.Conclusions Use of the novel orthodontic e-resource by 4th
year undergraduate students over a 6-week period did not result in a significant
improvement in subject knowledge. However, the e-learning has proven popular
among undergraduates and the resources will continue to be refined.
PMID- 27514364
TI - The unbearable lightness of simplicity.
PMID- 27514362
TI - Discovery of HLA-B*58:80, a novel HLA-B*58 variant, in a Taiwanese bone marrow
donor.
AB - One nucleotide substitution at residue 133 of HLA-B*58:01:01:01 results in a
novel allele, HLA-B*58:80.
PMID- 27514363
TI - Pemphigus foliaceus with circinated plaques and neutrophil pustules.
AB - Pemphigus is a group of autoimmune intraepidermal bullous diseases; being
pemphigus foliaceus (PF) and pemphigus vulgaris (PV) the most common subtypes.
Pustular variants are scarcely reported for both PV and PF. The purpose of this
manuscript was to describe the clinical, microscopic and immunologic findings of
an atypical case of PF presenting with pustules, including a review of the
literature. PF is described as blisters and because this entity is rare, it is
not known for the general medical community that they are other clinical features
that can be seen as this one we present here with pustules.
PMID- 27514365
TI - Characterization of loxoprofen transport in Caco-2 cells: the involvement of a
proton-dependent transport system in the intestinal transport of loxoprofen.
AB - Loxoprofen, a propionate non-steroidal anti-inflammatory drug (NSAID), is used
widely in East Asian countries. However, little is known about the transport
mechanisms contributing to its intestinal absorption. The objectives of this
study were to characterize the intestinal transport of loxoprofen using the human
intestinal Caco-2 cell model. The transport of loxoprofen was investigated in
cellular uptake studies. The uptake of loxoprofen into Caco-2 cells was pH- and
concentration-dependent, and was described by a Michaelis-Menten equation with
passive diffusion (Km : 4.8 mm, Vmax : 142 nmol/mg protein/30 s, and Kd : 2.2
MUl/mg protein/30 s). Moreover, the uptake of loxoprofen was inhibited by a
typical monocarboxylate transporter (MCT) inhibitor as well as by various
monocarboxylates. The uptake of [14 C] l-lactic acid, a typical MCT substrate, in
Caco-2 cells was saturable with relatively high affinity for MCT. Because
loxoprofen inhibited the uptake of [14 C] l-lactic acid in a noncompetitive
manner, it was unlikely that loxoprofen uptake was mediated by high-affinity
MCT(s). Our results suggest that transport of loxoprofen in Caco-2 cells is, at
least in part, mediated by a proton-dependent transport system. Copyright (c)
2016 John Wiley & Sons, Ltd.
PMID- 27514347
TI - Evaluating denture cleanliness of patients in a regional dental hospital.
AB - Aims To evaluate the quality of clinical record keeping and determine quality of
denture cleanliness; record baseline denture cleanliness for 60 patients;
introduce denture hygiene instruction (DHI); and then re-assess the patients for
improvement and enhanced record keeping.Methods Analysis of patients' denture
hygiene instruction record keeping (n = 60) was undertaken retrospectively. The
Denture Cleanliness Index (DCI) was utilised to assess denture cleanliness (best
score 0, worst score 4). Baseline DCI scores were taken and individual DHI was
delivered. After one month, patients were reviewed and scored, with record
keeping quality analysed.Results At baseline, 11.7% (n = 7) of patients had DCI
scores of <=2, improving to 93.8% (n = 45) after one month, demonstrating short
term improvement in denture cleanliness. Only 63% (n = 38) of patients had
evidence of a record of DHI within their notes at baseline, improving to 100% at
recall.Conclusions New patient information leaflet and clinical guidelines on
denture hygiene have been written and implemented. The results of this study
suggest that this may be a relatively straightforward method to achieve a short
term improvement in denture cleanliness. The implementation of a DCI score is
helpful in allowing patients to improve denture hygiene and its wider use is
supported.
PMID- 27514366
TI - Systematic review of interventions for depression and anxiety in persons with
inflammatory bowel disease.
AB - BACKGROUND: Depression and anxiety are common in inflammatory bowel disease (IBD)
and can affect disease outcomes, including quality of life and success of disease
treatment. Successful management of psychiatric comorbidities may improve
outcomes, though the effectiveness of existing treatments in IBD is unknown.
METHODS: We searched multiple online databases from inception until March 25,
2015, without restrictions on language, date, or location of publication. We
included controlled clinical trials conducted in persons with IBD and depression
or anxiety. Two independent reviewers reviewed all abstracts and full-text
articles and extracted information including trial and participant
characteristics. We also assessed the risk of bias. RESULTS: Of 768 unique
abstracts, we included one trial of pharmacological anxiety treatment in IBD (48
participants), which found an improvement in anxiety symptoms (p < 0.001). There
was a high risk of bias in this trial. We found no controlled clinical trials on
the treatment of depression in persons with IBD and depression and no controlled
clinical trials reporting on psychological interventions for anxiety or
depression in IBD. CONCLUSIONS: Only one trial examined an intervention for
anxiety in adults with IBD and no trials studied depression in adults with IBD.
The level of evidence is low because of the risk of bias and limited evidence.
PMID- 27514367
TI - PCR detection of Burkholderia multivorans in water and soil samples.
AB - BACKGROUND: Although semi-selective growth media have been developed for the
isolation of Burkholderia cepacia complex bacteria from the environment, thus far
Burkholderia multivorans has rarely been isolated from such samples. Because
environmental B. multivorans isolates mainly originate from water samples, we
hypothesized that water rather than soil is its most likely environmental niche.
The aim of the present study was to assess the occurrence of B. multivorans in
water samples from Flanders (Belgium) using a fast, culture-independent PCR
assay. RESULTS: A nested PCR approach was used to achieve high sensitivity, and
specificity was confirmed by sequencing the resulting amplicons. B. multivorans
was detected in 11 % of the water samples (n = 112) and 92 % of the soil samples
(n = 25) tested. The percentage of false positives was higher for water samples
compared to soil samples, showing that the presently available B. multivorans
recA primers lack specificity when applied to the analysis of water samples.
CONCLUSIONS: The results of the present study demonstrate that B. multivorans DNA
is commonly present in soil samples and to a lesser extent in water samples in
Flanders (Belgium).
PMID- 27514368
TI - New insights into discrepancies between self-reported and accelerometer-measured
moderate to vigorous physical activity among women - the mPED trial.
AB - BACKGROUND: The aims of this report were 1) to describe the duration of moderate
to vigorous physical activity (MVPA) and the proportion of participants meeting
the recommended criterion of at least 150 min of MVPA per week as measured by the
7 Day Physical Activity Recall Questionnaire (7D-PAR) and accelerometer among
women who were enrolled in the mPED trial; 2) to assess the level of agreement of
the two measures using a Bland-Altman plot; and 3) to describe the positive and
negative predictive values (PPV and NPV, respectively) of meeting the guidelines
by calculating the percentage of women meeting the physical activity
recommendation by the 7D-PAR who also met this recommendation based on data from
the accelerometer. METHODS: Baseline data on duration of MVPA from the mPED trial
were analyzed for 215 women. Among the women who met the recommended criterion by
the 7D-PAR (self-report), we calculated the proportion of individuals who also
met it by the accelerometer (objective measure). A Bland Altman Plot was used to
assess concordance between the two measures. RESULTS: The mean age was 52.4 (+/
11.2) years; 54.4 % were white; and 48.8 % were single or divorced. While median
MVPA was 160 min/week by the 7D-PAR, it was only 24 min/week in the
accelerometer. A total of 117 women met the 150-min criterion by the 7D-PAR. Of
these, only 18 also met the criterion by the objective measure (PPV 15.4 %, 95 %
CI 9.4-23.2 %). Among the 98 women who did not meet the criterion by the 7D-PAR,
none met it by the accelerometer (NPV 100 %). A Bland Altman plot showed the mean
difference of +145 min between the two measures with a 95 % limit of agreement at
+ 471 to -181 min. CONCLUSIONS: The large discrepancy between the self-reported
and objective measures of MVPA meeting the 150-min criterion suggests that self
reported physical activity measures should be used with caution in intervention
studies. While our data suggest that self-report could be used to identify a
physically inactive sample, it would be likely to over-estimate the proportions
of women who become active in one or both arms of trials of interventions
promoting MVPA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280812.
PMID- 27514369
TI - Multiple systemic embolism in infective endocarditis underlying in Barlow's
disease.
AB - BACKGROUND: Systemic embolism, especially septic embolism, is a severe
complication of infective endocarditis (IE). However, concurrent embolism to the
brain, coronary arteries, and spleen is very rare. Because of the risk of
hemorrhage or visceral rupture, anticoagulants are recommended only if an
indication is present, e.g. prosthetic valve. Antiplatelet therapy in IE is
controversial, but theoretically, this therapy has the potential to prevent and
treat thrombosis and embolism in IE. Unfortunately, clinical trial results have
been inconclusive. CASE PRESENTATION: We describe a previously healthy 50-year
old man who presented with dysarthria secondary to bacterial endocarditis with
multiple cerebral, coronary, splenic, and peripheral emboli; antibiotic therapy
contributed to the multiple emboli. Emergency splenectomy was performed, with
subsequent mitral valve repair. Pathological examination confirmed mucoid
degeneration and mitral valve prolapse (Barlow's disease) as the underlying
etiology of the endocardial lesion. Continuous antibiotics were prescribed,
postoperatively. Transthoracic echocardiography at 1.5, 3, and 6 months after the
onset of his illness showed no severe regurgitation, and there was no respiratory
distress, fever, or lethargy during follow-up. CONCLUSIONS: Although antibiotic
use in IE carries a risk of septic embolism, these drugs have bactericidal and
antithrombotic benefits. It is important to consider that negative blood culture
and symptom resolution do not confirm complete elimination of bacteria. However,
vegetation size and Staphylococcus aureus infection accurately predict
embolization. It is also important to consider that bacteria can be segregated
from the microbicide when embedded in platelets and fibrin. Therefore,
antimicrobial therapy with concurrent antiplatelet therapy should be considered
carefully.
PMID- 27514370
TI - Biomimetic coatings enhance tribocorrosion behavior and cell responses of
commercially pure titanium surfaces.
AB - Biofunctionalized surfaces for implants are currently receiving much attention in
the health care sector. Our aims were (1) to create bioactive Ti-coatings doped
with Ca, P, Si, and Ag produced by microarc oxidation (MAO) to improve the
surface properties of biomedical implants, (2) to investigate the TiO2 layer
stability under wear and corrosion, and (3) to evaluate human mesenchymal stem
cells (hMSCs) responses cultured on the modified surfaces. Tribocorrosion and
cell experiments were performed following the MAO treatment. Samples were divided
as a function of different Ca/P concentrations and treatment duration. Higher Ca
concentration produced larger porous and harder coatings compared to the
untreated group (p < 0.001), due to the presence of rutile structure. Free
potentials experiments showed lower drops (-0.6 V) and higher coating lifetime
during sliding for higher Ca concentration, whereas lower concentrations
presented similar drops (-0.8 V) compared to an untreated group wherein the drop
occurred immediately after the sliding started. MAO-treated surfaces improved the
matrix formation and osteogenic gene expression levels of hMSCs. Higher Ca/P
ratios and the addition of Ag nanoparticles into the oxide layer presented better
surface properties, tribocorrosive behavior, and cell responses. MAO is a
promising technique to enhance the biological, chemical, and mechanical
properties of dental implant surfaces.
PMID- 27514371
TI - Combination treatment with mirabegron and solifenacin in patients with overactive
bladder: exploratory responder analyses of efficacy and evaluation of patient
reported outcomes from a randomized, double-blind, factorial, dose-ranging, Phase
II study (SYMPHONY).
AB - PURPOSE: This large dose-ranging study explored the benefits of different
combinations of mirabegron and solifenacin on health-related quality of life
(HRQoL), based on patient-reported outcomes (PROs), and patients ('responders')
achieving clinically meaningful improvements in efficacy and HRQoL. METHODS:
SYMPHONY (NCT01340027) was a Phase II, placebo- and monotherapy-controlled, dose
ranging, 12-week trial. Adult patients with overactive bladder (OAB) for >=3
months were randomized to 1 of 12 groups: 6 combination (solifenacin 2.5/5/10 mg
+ mirabegron 25/50 mg), 5 monotherapy (solifenacin 2.5/5/10 mg, or mirabegron
25/50 mg), or placebo. Change from baseline to end of treatment was assessed,
versus placebo and solifenacin 5 mg in: PROs (OAB-q [Symptom Bother/total HRQoL]
and Patient Perception of Bladder Condition score), and responders achieving
minimally important differences (MIDs) in PROs and predetermined clinically
meaningful improvements in efficacy (e.g. <8 micturitions/24 h). Changes in PROs
and responders were analysed using an ANCOVA model and logistic regression,
respectively. RESULTS: The Full Analysis Set included 1278 patients. Combination
therapy of solifenacin 5/10 mg + mirabegron 25/50 mg significantly improved PROs
versus solifenacin 5 mg and placebo, and significantly more responders achieved
MIDs in PROs and efficacy. Micturition frequency normalization was approximately
twofold greater with 10 + 25 mg (OR 2.06 [95 % CI 1.11, 3.84; p = 0.023]) and 5 +
50 mg (OR 1.91 [95 % CI 1.14, 3.21; p = 0.015]) versus solifenacin 5 mg.
CONCLUSION: Combining mirabegron 25/50 mg and solifenacin 5/10 mg improves
objective and subjective efficacy outcomes compared with placebo or solifenacin 5
mg.
PMID- 27514372
TI - Unsolved challenges of clinical whole-exome sequencing: a systematic literature
review of end-users' views.
AB - BACKGROUND: Whole-exome sequencing (WES) consists in the capture, sequencing and
analysis of all exons in the human genome. Originally developed in the research
context, this technology is now increasingly used clinically to inform patient
care. The implementation of WES into healthcare poses significant organizational,
regulatory, and ethical hurdles, which are widely discussed in the literature.
METHODS: In order to inform future policy decisions on the integration of WES
into standard clinical practice, we performed a systematic literature review to
identify the most important challenges directly reported by technology users.
RESULTS: Out of 2094 articles, we selected and analyzed 147 which reported a
total of 23 different challenges linked to the production, analysis, reporting
and sharing of patients' WES data. Interpretation of variants of unknown
significance, incidental findings, and the cost and reimbursement of WES-based
tests were the most reported challenges across all articles. CONCLUSIONS: WES is
already used in the clinical setting, and may soon be considered the standard of
care for specific medical conditions. Yet, technology users are calling for
certain standards and guidelines to be published before this technology replaces
more focused approaches such as gene panels sequencing. In addition, a number of
infrastructural adjustments will have to be made for clinics to store, process
and analyze the amounts of data produced by WES.
PMID- 27514373
TI - Cost of rotavirus diarrhea for programmatic evaluation of vaccination in Vietnam.
AB - BACKGROUND: Rotavirus is the most common etiology of diarrhea-associated
hospitalizations and clinic visits in Vietnamese children < 5 years old. To
estimate the economic burden of rotavirus-associated formal healthcare
encounters, an economic study was conducted. METHODS: A cost-of-illness study was
performed from a societal perspective. Data were collected from children below
the age of five years who presented to a clinic or hospital with symptoms of
acute gastroenteritis (AGE). Patient-specific information on resource use and
cost was obtained through caregiver interviews and medical chart review. Costs
are presented in 2014 US dollar ($). RESULTS: A total of 557 children with
symptoms of AGE were enrolled from March through June 2009, with mean age of 16.5
months. Of the 340 outpatients and 217 admitted patients enrolled, 41 % tested
rotavirus positive. It was found that, from a societal perspective, the mean
total cost of AGE was $175. Costs of patients with and without rotavirus were
$217 and $158, respectively. From multiple regression analysis, it was found that
rotavirus infection, patient age and receiving oral rehydration solution before
visiting health facility had significant effect on the costs. CONCLUSIONS: This
study clearly demonstrated substantial economic burden of AGE including rotavirus
disease. They were significantly greater than the previously reported cost
estimates in Vietnam. These updated costs of illness result in more favorable
vaccine cost-effectiveness than in previous economic evaluations.
PMID- 27514374
TI - Association between mesothelin expression and survival outcomes in patients with
triple-negative breast cancer: a protocol for a systematic review.
AB - BACKGROUND: Mesothelin is a membrane-bound glycoprotein. Although the biologic
function of mesothelin is not very clear, researchers have found that it plays a
role in the survival, proliferation, and migration of tumor cells. Identified as
a tumor-associated biomarker, mesothelin is more often overexpressed in triple
negative breast cancer (TNBC) than in common luminal breast tumor subtype or
normal tissues. The objective of this review is to determine the association
between the expression of mesothelin and overall survival in patients with TNBC.
METHODS/DESIGN: We will search the following electronic databases: MEDLINE,
EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and
Web of Science with no time or language restriction. Prospective or retrospective
longitudinal studies that investigate mesothelin expression in TNBC or the
prognosis of TNBC with mesothelin baseline measurement will be selected. Two
reviewers will independently assess every abstract or full text for inclusion.
Data on clinical outcomes, as well as on study design, research setting, study
population, demographic characteristics of the participants, and methodological
quality, will be extracted using a structured codebook developed by the authors.
A pooled measure of associations will be assessed through meta-analyses if
appropriate. Heterogeneity across the included studies will be evaluated using
the I (2) statistics. Findings will be reported according to the Meta-Analysis of
Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The
quality of evidence and risk of bias of the studies will be evaluated.
DISCUSSION: The aim of this systematic review is to synthesize the evidence
regarding the association between the expression of mesothelin and the survival
outcomes of patients with TNBC. A better understanding of the expression
frequency and prognostic value of mesothelin in TNBC will be essential to
identifying a novel therapeutic target. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
CRD42016036212.
PMID- 27514375
TI - Transcriptomics of liver and muscle in Holstein cows genetically divergent for
fertility highlight differences in nutrient partitioning and inflammation
processes.
AB - BACKGROUND: The transition between pregnancy and lactation is a major
physiological change for dairy cows. Complex systemic and local processes
involving regulation of energy balance, galactopoiesis, utilisation of body
reserves, insulin resistance, resumption of oestrous cyclicity and involution of
the uterus can affect animal productivity and hence farm profitability. Here we
used an established Holstein dairy cow model of fertility that displayed genetic
and phenotypic divergence in calving interval. Cows had similar genetic merit for
milk production traits, but either very good genetic merit for fertility traits
('Fert+'; n = 8) or very poor genetic merit for fertility traits ('Fert-'; n =
8). We used RNA sequencing to investigate gene expression profiles in both liver
and muscle tissue biopsies at three distinct time-points: late pregnancy, early
lactation and mid lactation (-18, 1 and 147 days relative to parturition,
respectively). RESULTS: We found 807 and 815 unique genes to be differentially
expressed in at least one time-point in liver and muscle respectively, of which
79 % and 83 % were only found in a single time-point; 40 and 41 genes were found
differentially expressed at every time-point indicating possible systemic or
chronic dysregulation. Functional annotation of all differentially expressed
genes highlighted two physiological processes that were impacted at every time
point in the study, These were immune and inflammation, and metabolic, lipid and
carbohydrate-binding. CONCLUSION: These pathways have previously been identified
by other researchers. We show that several specific genes which are
differentially regulated, including IGF-1, might impact dairy fertility. We
postulate that an increased burden of reactive oxidation species, coupled with a
chronic inflammatory state, might reduce dairy cow fertility in our model.
PMID- 27514376
TI - The estrogen-related receptors (ERRs): potential targets against bone loss.
AB - Bone loss and the resulting skeletal fragility is induced by several pathological
or natural conditions, the most prominent of which being aging as well as the
decreased levels of circulating estrogens in post-menopause females. To date,
most treatments against bone loss aim at preventing excess bone resorption. We
here summarize data indicating that the estrogen-related receptors (ERRs) alpha
and gamma prevent bone formation. Inhibiting these receptors may thus constitute
an anabolic approach by increasing bone formation.
PMID- 27514377
TI - Female cats, but not males, adjust responsiveness to arousal in the voice of
kittens.
AB - BACKGROUND: The infant cry is the most important communicative tool to elicit
adaptive parental behaviour. Sex-specific adaptation, linked to parental
investment, may have evolutionary shaped the responsiveness to changes in the
voice of the infant cries. The emotional content of infant cries may trigger
distinctive responsiveness either based on their general arousing properties,
being part of a general affect encoding rule, or based on affective perception,
linked to parental investment, differing between species. To address this
question, we performed playback experiments using infant isolation calls in a
species without paternal care, the domestic cat. We used kitten calls recorded in
isolation contexts inducing either Low arousal (i.e., isolation only) or High
arousal (i.e., additional handling), leading to respective differences in escape
response of the kittens. We predicted that only females respond differently to
playbacks of Low versus High arousal kitten isolation calls, based on sex
differences in parental investment. RESULTS: Findings showed sex-specific
responsiveness of adult cats listening to kitten isolation calls of different
arousal conditions, with only females responding faster towards calls of the High
versus the Low arousal condition. Breeding experience of females did not affect
the result. Furthermore, female responsiveness correlated with acoustic
parameters related to spectral characteristics of the fundamental frequency (F0):
Females responded faster to kitten calls with lower F0 at call onset, lower
minimum F0 and a steeper slope of the F0. CONCLUSIONS: Our study revealed sex
specific differences in the responsiveness to kitten isolation calls of different
arousal conditions independent of female breeding experience. The findings
indicated that features of F0 are important to convey the arousal state of an
infant. Taken together, the results suggest that differences in parental
investment evolutionary shaped responsiveness (auditory sensitivity/ motivation)
to infant calls in a sex-specific manner in the domestic cat.
PMID- 27514378
TI - Lipopolysaccharide induces SBD-1 expression via the P38 MAPK signaling pathway in
ovine oviduct epithelial cells.
AB - BACKGROUND: Beta defensins are secreted from ovine oviduct epithelial cells
(OOECs) in response to microbial infection, and are potential alternatives to
antibiotic agents in the treatment of microorganism infection, particularly given
the abuse of antibiotic agents and the increasing number of drug-resistant
bacteria. The aberrant expression of defensins may result in disorders involving
organ and oviduct inflammation, such as salpingitis. METHODS: In the present
study, we investigated the effects of LPS on the mRNA expression levels of sheep
beta-defensin-1 (SBD-1) in ovine oviduct epithelial cells. The OOECs in vitro
culturing system were established and treated with different concentrations of
LPS for indicated time. In addition, MAPK inhibitors and TLR4 antibodies were
pretreated to investigate the potential mechanism which involves in LPS
regulating SBD-1 expression. RESULTS: LPS markedly upregulated SBD-1 expression
in a concentration- and time-dependent manner. Treatment with 100 ng/mL LPS
resulted in the phosphorylation of JNK, ERK and P38 MAPK. Interestingly, the LPS
stimulated SBD-1 expression was attenuated by pretreatment with the P38 MAPK
inhibitors SB203580 and SB202190 but not the JNK inhibitor SP600125, while the
ERK inhibitor PD98059 had a minor effect. Furthermore, treatment with a Toll-like
receptor 4 (TLR4) neutralizing antibody significantly decreased P38 MAPK
phosphorylation and LPS induced SBD-1 expression. CONCLUSIONS: Together, these
findings suggest that SBD-1 is upregulated by LPS via the TLR4 receptor, mainly
through the P38 MAPK signaling pathway in ovine oviduct epithelial cells to
protect the ovine oviduct epithelium from pathogen invasion.
PMID- 27514379
TI - Self-reported practices among traditional birth attendants surveyed in western
Kenya: a descriptive study.
AB - BACKGROUND: The high rate of home deliveries conducted by unskilled birth
attendants in resource-limited settings is an important global health issue
because it is believed to be a significant contributing factor to maternal and
newborn mortality. Given the large number of deliveries that are managed by
unskilled or traditional birth attendants outside of health facilities, and the
fact that there is on-going discussion regarding the role of traditional birth
attendants in the maternal newborn health (MNH) service continuum, we sought to
ascertain the practices of traditional birth attendants in our catchment area.
The findings of this descriptive study might help inform conversations regarding
the roles that traditional birth attendants can play in maternal-newborn health
care. METHODS: A structured questionnaire was used in a survey that included one
hundred unskilled birth attendants in western Kenya. Descriptive statistics were
employed. RESULTS: Inappropriate or outdated practices were reported in relation
to some obstetric complications and newborn care. Encouraging results were
reported with regard to positive relationships that traditional birth attendants
have with their local health facilities. Furthermore, high rates of referral to
health facilities was reported for many common obstetric emergencies and similar
rates for reporting of pregnancy outcomes to village elders and chiefs.
CONCLUSIONS: Potentially harmful or outdated practices with regard to maternal
and newborn care among traditional birth attendants in western Kenya were
revealed by this study. There were high rates of traditional birth attendant
referrals of pregnant mothers with obstetric complications to health facilities.
Policy makers may consider re-educating and re-defining the roles and
responsibilities of traditional birth attendants in maternal and neonatal health
care based on the findings of this survey.
PMID- 27514382
TI - Rapid Development of Omentum Metastasis Following Stereotactic Body Radiotherapy
(Sbrt) to Para-Aortic Lymph Nodes from Colon Cancer.
PMID- 27514380
TI - Traditional medicine practices among community members with diabetes mellitus in
Northern Tanzania: an ethnomedical survey.
AB - BACKGROUND: Diabetes is a growing burden in sub-Saharan Africa where traditional
medicines (TMs) remain a primary form of healthcare in many settings. In
Tanzania, TMs are frequently used to treat non-communicable diseases, yet little
is known about TM practices for non-communicable diseases like diabetes. METHODS:
Between December 2013 and June 2014, we assessed TM practices, including types,
frequencies, reasons, and modes, among randomly selected community members. To
further characterize TMs relevant for the local treatment of diabetes, we also
conducted focus groups and semi-structured interviews with key informants.
RESULTS: We enrolled 481 adults of whom 45 (9.4 %) had diabetes. The prevalence
of TM use among individuals with diabetes was 77.1 % (95 % CI 58.5-89.0 %), and
the prevalence of using TMs and biomedicines concurrently was 37.6 % (95 % CI
20.5-58.4 %). Many were using TMs specifically to treat diabetes (40.3 %; 95 % CI
20.5-63.9), and individuals with diabetes reported seeking healthcare from
traditional healers, elders, family, friends, and herbal vendors. We identified
several plant-based TMs used toward diabetes care: Moringa oleifera, Cymbopogon
citrullus, Hagenia abyssinica, Aloe vera, Clausena anisata, Cajanus cajan,
Artimisia afra, and Persea americana. CONCLUSIONS: TMs were commonly used for
diabetes care in northern Tanzania. Individuals with diabetes sought healthcare
advice from many sources, and several individuals used TMs and biomedicines
together. The TMs commonly used by individuals with diabetes in northern Tanzania
have a wide range of effects, and understanding them will more effectively shape
biomedical practitices and public health policies that are patient-centered and
sensitive to TM preferences.
PMID- 27514381
TI - Relationship between TMEM16A/anoctamin 1 and LRRC8A.
AB - TMEM16A/anoctamin 1/ANO1 and VRAC/LRRC8 are independent chloride channels
activated either by increase in intracellular Ca(2+) or cell swelling,
respectively. In previous studies, we observed overlapping properties for both
types of channels. (i) TMEM16A/ANO1 and LRRC8 are inhibited by identical
compounds, (ii) the volume-regulated anion channel VRAC requires
compartmentalized Ca(2+) increase to be fully activated, (iii) anoctamins are
activated by cell swelling, (iv) both channels have a role for apoptotic cell
death, (v) both channels are possibly located in lipid rafts/caveolae like
structures, and (vi) VRAC and anoctamin 1 currents are not additive when each are
fully activated. In the present study, we demonstrate in different cell types
that loss of LRRC8A expression not only inhibited VRAC, but also attenuated
Ca(2+) activated Cl(-) currents. Moreover, expression of LRRC8A enhanced Ca(2+)
activated Cl(-) currents, and both LRRC8A and ANO1 could be coimmunoprecipitated.
We found that LRRC8A becomes accessible to biotinylation upon exposure to
hypotonic bath solution, while membrane capacitance was not enhanced. When
intracellular Ca(2+) was increased in ANO1-expressing cells, the membrane
capacitance was enhanced and increased binding of FM4-64 to the membrane was
observed. As this was not seen in cells lacking ANO1 expression, a role of ANO1
for exocytosis was suggested. We propose that ANO1 and LRRC8A are activated in
parallel. Thus, ionomycin or purinergic stimulation will not only activate ANO1
but also LRRC8 currents. Cell swelling will not only activate LRRC8/VRAC, but
also stimulate ANO1 currents by enhancing compartmentalized Ca(2+) increase
and/or through swelling induced autocrine release of ATP.
PMID- 27514384
TI - Retraction Note to: Assessment of neuromuscular block at the orbicularis oris,
corrugator supercilii, and adductor pollicis muscles.
PMID- 27514383
TI - Effect of transcatheter aortic valve implantation on intraoperative left
ventricular end-diastolic pressure.
AB - Transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis
is a less invasive alternative to surgical aortic valve replacement. Despite
this, careful anesthetic management, especially strict control of blood pressure
and fluid management, is necessary. During TAVI, normalization of left
ventricular afterload due to aortic balloon valvuloplasty and prosthetic valve
deployment is expected to result in rapid improvement of systolic function and
consequent improvement in diastolic function. However, the early effect of TAVI
on left ventricular diastolic function is less clear. We hypothesized that TAVI
induces a rapid decrease in left ventricular end-diastolic pressure (LVEDP) after
valve deployment. This retrospective observational study included 71 patients who
had undergone TAVI using the transfemoral approach with a balloon-expandable
valve under general anesthesia. Intraoperative LVEDP was measured using an
intracardiac catheter. The severity of residual aortic regurgitation (AR) was
assessed using the Sellers criteria. The mean (SD) LVEDP was 17.8 (5.3) mmHg just
before TAVI and increased significantly to 27.3 (8.2) mmHg immediately after
prosthetic valve deployment (p < 0.0001). The change in LVEDP was 8.7 (8.6) mmHg
in patients with low residual AR (Sellers <=1) and 11.0 (7.1) mmHg in those with
high residual AR (Sellers >=2); however, this difference was not significant. No
correlation was found between the LVEDP change and intraoperative fluid balance.
In conclusion, LVEDP increased significantly in the early period after valve
deployment during TAVI, regardless of residual AR severity. It was suggested that
the tolerability of fluid load could be reduced at that time.
PMID- 27514385
TI - Vital role for the J-domain protein Mdj1 in asexual development, multiple stress
tolerance, and virulence of Beauveria bassiana.
AB - Mdj1 is a member of the Hsp40 family containing a DnaJ or J domain. Here, we have
examined the functions of an Mdj1 orthologue (56.68 kDa) in Beauveria bassiana, a
filamentous fungal insect pathogen widely applied in biological control of insect
pests. Deletion of mdj1 in B. bassiana resulted in significant growth defects on
a variety of complex and minimal media. The Deltamdj1 mutant exhibited not only a
drastic reduction (92 %) in aerial conidiation during optimal cultivation but
also a remarkable decrease (77 %) in submerged blastospore production. Compared
to wild-type, the deletion mutant was significantly more sensitive to the
stresses of cell wall perturbation, high osmolarity, oxidation, carbendazim
fungicide, several metal ions, and acidic/alkaline pH during conidial germination
and/or colony growth. In the mutant, conidial thermotolerance and UV-B resistance
decreased by 61 and 25 %, respectively, and virulence to Galleria mellonella
larvae was largely attenuated. Transcript levels of many phenotype-related genes
were drastically suppressed in the absence of mdj1, accompanied with impaired
cell walls and reduced intracellular anti-stress molecules, including superoxide
dismutases, catalases, glycerol, trehalose, and mannitol. These data indicate
that Mdj1 plays a vital role in normal fungal development and contributes
significantly to the biological control potential of B. bassiana against insect
pests.
PMID- 27514387
TI - Correction.
PMID- 27514386
TI - Sugiyamaella mastotermitis sp. nov. and Papiliotrema odontotermitis f.a., sp.
nov. from the gut of the termites Mastotermes darwiniensis and Odontotermes
obesus.
AB - Two novel yeast species were isolated from the guts of two different termite
species. A new member of the genus Sugiyamaella was isolated from the hindgut and
nest material of the lower Australian termite Mastotermes darwiniensis. The
second novel yeast species, isolated from the higher termite Odontotermes obesus,
was identified as a member of the genus Papiliotrema. Both yeast species were
able to hydrolyse xylan, methylumbelliferyl beta-xylobiose and methylumbelliferyl
beta-xylotriose. The ability to debranch different hemicellulose side chains and
growth without the addition of external vitamins was observed. A symbiotic role
of the novel yeast species is indicated, especially in respect to xylan
degradation and the production of vitamins. Here, we describe these species as
Sugiyamaella mastotermitis sp. nov., MycoBank 816574 (type strain MD39VT=DSM
100793T=CBS 14182T), and Papiliotrema odontotermitis f.a., sp. nov., MycoBank
816575 (type strain OO5T=DSM 100791T=CBS 14181T). Additionally, we transfer
Candida qingdaonensis to the genus Sugiyamaella and propose the following
combination: Sugiyamaella qingdaonensis f.a., comb. nov., MycoBank 816576.
PMID- 27514388
TI - [Quality in urology].
PMID- 27514390
TI - The Iodine Status of Queensland Preschool Children After the Introduction of
Mandatory Iodine Fortification in Bread: An Exploratory Study Using a Convenience
Sample.
AB - Introduction Appropriate dietary iodine is essential for thyroid hormone
synthesis, especially in young children. Following an iodine fortification in
bread initiative, approximately 6 % of Australian preschool children were
expected to have an excessive iodine status. The aim of this study was to
document the current iodine status of preschool children using urinary iodine
concentration (UIC) as a biomarker of iodine intake. Methods A convenience sample
of fifty-one preschool children, aged 2-3 years, were recruited from south east
Queensland. UIC was ascertained from spot morning and afternoon urine samples
collected on two consecutive days and food frequency questionnaires were
completed for each participant. Dietary iodine intake was extrapolated from UIC
assuming 90 % of dietary iodine is excreted in urine and a urine volume of 0.5
L/day. Results A median UIC of 223.3 MUg/L was found. The calculated median
dietary iodine intake was 124.8 MUg/day (SD 47.0) with 9.8 % of samples above the
upper level of 200 MUg for dietary iodine for children within this age group. No
foods were associated with UIC. Discussion Limited by sample size and recruitment
strategies, no association was found between usual food intake and UIC.
Extrapolated dietary iodine intake indicated that children within this cohort
consumed adequate amounts of dietary iodine, although the number of children
consuming above the upper limit of 300 MUg/day was almost double of expected. The
development of a UIC criteria to assess appropriate parameters for varying
degrees of iodine status is required for the monitoring of iodine nutrition in
this vulnerable age group.
PMID- 27514389
TI - The Impact of Race and Neighborhood Racial Composition on Preventable
Readmissions for Diabetic Medicare Home Health Beneficiaries.
AB - BACKGROUND: The recommended home health financial penalty program for preventable
readmission does not factor race/ethnicity and neighborhood racial compositions
into the determination of preventable readmission rates. Home health agencies may
avoid beneficiaries from certain racial/ethnic groups and neighborhoods if these
two factors have an effect on preventable readmissions. We examined the
association between preventable readmissions with race/ethnicity and neighborhood
racial composition. METHODS: Several 2009 national data were used, such as the
Master Beneficiary Summary File, Medicare Provider Analysis and Review File, and
Outcome Assessment Information Set. Our sample consisted of diabetic Medicare
home health beneficiaries (African-Americans and Whites only). We analyzed
predictors of time-to-first 30-day preventable readmission, including short/long
term diabetic complications, chronic obstructive pulmonary disease/asthma,
bacterial pneumonia, dehydration, urinary tract infection, hypertension, heart
failure, angina without procedure, uncontrolled diabetes, and lower-extremity
amputation. RESULTS: There were 86,567, 17,262, and 11,392 observations in
neighborhoods with low (6 % African-Americans), moderate (35 % African
Americans), and high (76 % African-Americans) density of African-Americans,
respectively. Using Cox regression models, we found that in neighborhoods with
moderate and high density of African-Americans, African-Americans had 21 %
(hazard ratio (HR) 1.21; 95 % confidence interval (CI) 1.04-1.39) and 24 % (HR
1.24; 95 % CI 1.01-1.52) significantly higher hazards of 30-day preventable
readmissions than Whites, respectively. CONCLUSION: Race and neighborhood racial
compositions are beyond home health providers' control. These two factors should
be considered as covariates for the preventable readmissions in the recommended
home health financial penalty program.
PMID- 27514391
TI - Enhancing HIV Treatment Access and Outcomes Amongst HIV Infected Children and
Adolescents in Resource Limited Settings.
AB - Introduction Increasing access to HIV-related care and treatment for children
aged 0-18 years in resource-limited settings is an urgent global priority. In
2011-2012 the percentage increase in children accessing antiretroviral therapy
was approximately half that of adults (11 vs. 21 %). We propose a model for
increasing access to, and retention in, paediatric HIV care and treatment in
resource-limited settings. Methods Following a rapid appraisal of recent
literature seven main challenges in paediatric HIV-related care and treatment
were identified: (1) lack of regular, integrated, ongoing HIV-related diagnosis;
(2) weak facility-based systems for tracking and retention in care; (3)
interrupted availability of dried blood spot cards (expiration/stock outs); (4)
poor quality control of rapid HIV testing; (5) supply-related gaps at health
facility-laboratory interface; (6) poor uptake of HIV testing, possibly relating
to a fatalistic belief about HIV infection; (7) community-associated reasons e.g.
non-disclosure and weak systems for social support, resulting in poor retention
in care. Results To increase sustained access to paediatric HIV-related care and
treatment, regular updating of Policies, review of inter-sectoral Plans (at
facility and community levels) and evaluation of Programme implementation and
impact (at national, subnational, facility and community levels) are non
negotiable critical elements. Additionally we recommend the intensified
implementation of seven main interventions: (1) update or refresher messaging for
health care staff and simple messaging for key staff at early childhood
development centres and schools; (2) contact tracing, disclosure and retention
monitoring; (3) paying particular attention to infant dried blood spot (DBS)
stock control; (4) regular quality assurance of rapid HIV testing procedures; (5)
workshops/meetings/dialogues between health facilities and laboratories to
resolve transport-related gaps and to facilitate return of results to facilities;
(6) community leader and health worker advocacy at creches, schools, religious
centres to increase uptake of HIV testing and dispel fatalistic beliefs about
HIV; (7) use of mobile communication technology (m-health) and peer/community
supporters to maintain contact with patients. Discussion and Conclusion We
propose that this package of facility, community and family-orientated
interventions are needed to change the trajectory of the paediatric HIV epidemic
and its associated patterns of morbidity and mortality, thus achieving the double
dividend of improving HIV-free survival.
PMID- 27514392
TI - A Matched Comparison of Per Oral Endoscopic Myotomy to Laparoscopic Heller
Myotomy in the Treatment of Achalasia.
AB - BACKGROUND: Per oral endoscopic myotomy (POEM) is increasingly utilized to treat
patients with achalasia. Early results have demonstrated significant improvement
of symptoms, but there are concerns about postoperative reflux. With only limited
comparative data available, we sought to compare POEM to laparoscopic Heller
myotomy (LHM) with partial fundoplication. METHODS: This is a retrospective
review of 42 POEM and 84 LHM patients undergoing primary myotomy for achalasia.
Patients were matched by achalasia type, by Eckardt and dysphagia scores, and by
quality of life (QOL) metrics. Analysis at 6-12-month follow-up evaluated these
metrics, PPI use, pH, manometric, and endoscopic data. RESULTS: We matched 25
patients with achalasia types I (6), II (13), and III (6). Follow-up was longer
for LHM at 158.1 (36.5-272.9) weeks versus 36.2 (22.2-41.2) weeks (p = 0.001).
Eckardt scores, QOL metrics, and dysphagia significantly improved in both groups.
DeMeester scores and total percent time less than 4 were abnormal in both groups
and comparable (p = 0.925 and p = 0.838). Esophagitis was seen in 53.4 % (POEM)
and 31.6 % (LHM) (Yates' p = 0.91), and PPI use was equivalent at 36 %.
CONCLUSION: Early clinical outcomes are excellent with POEM and comparable to the
standard of care LHM. Long-term follow-up is required as concerns for reflux
persist.
PMID- 27514394
TI - The evolution of big ideas: Molecular biology has seen many grand visions come
and go and some others come back.
PMID- 27514393
TI - Association of serum adiponectin concentration with aortic arterial stiffness in
chronic kidney disease: from the KNOW-CKD study.
AB - BACKGROUND: High serum adiponectin levels predict all-cause and cardiovascular
mortality in chronic kidney disease (CKD). However, the relationship between
serum adiponectin concentration and arterial stiffness in CKD is not well
established. The aim of this study was to assess this relationship by measuring
pulse wave velocity (PWV) in CKD patients. METHODS: Serum adiponectin
concentration was measured in 716 CKD patients in the prospective KoreaN cohort
study for Outcome in patients With Chronic Kidney Disease. The study group
consisted of 415 men and 301 women; mean age was 53.1 years, and baseline
estimated glomerular filtration rate (eGFR) was 51 +/- 29 ml/min per 1.73 m2.
Heart to femoral PWV (hfPWV) and mean brachial to ankle PWV (baPWV) served as
indicators of aortic artery stiffness and arterial stiffness, respectively.
RESULTS: Increasing quartiles of serum adiponectin levels were associated with
women, lower eGFRs and body mass indices, and higher urinary albumin-creatinine
ratios. Serum adiponectin concentration also correlated with hfPWV and mean
baPWV, even after adjusting for age and sex. It independently associated with
hfPWV (B 0.028; 95 % confidence interval, 0.004-0.051; P = 0.020) but not mean
baPWV in a multivariable linear regression analysis. In a multivariable logistic
regression analysis, it correlated significantly with the highest quartile of
hfPWVs but not mean baPWVs. CONCLUSION: The independent and significant
correlation of serum adiponectin concentration with hfPWV in CKD patients
implicates adiponectin in CKD-associated aortic stiffness.
PMID- 27514395
TI - Prognostic significance of androgen receptor expression in invasive breast
cancer: transcriptomic and protein expression analysis.
AB - Differential prognostic roles of Androgen Receptor (AR) have been proposed in
breast cancer (BC) depending on tumour oestrogen receptor (ER) status. This study
aimed to evaluate the prognostic and/or predictive significance of AR expression
in invasive BC. In this study AR expression was studied on a large (n = 1141)
consecutive series of early-stage (I-III) BC using tissue microarray and
immunohistochemistry (IHC). AR mRNA expression was assessed in a subset of cases.
The prognostic impact of AR mRNA expression was externally validated using the
online BC gene expression data sets (n = 25 data sets, 4078 patients). Nuclear AR
IHC expression was significantly associated with features of good prognosis
including older age, smaller tumour size, lower grade and lobular histology
particularly in the ER-positive tumours. AR was associated with ER-related
markers GATA3, FOXa1, RERG and BEX1. Negative association was observed with HER2,
p53, Ki67, TK1, CD71 and AGTR1. AR Overexpression was associated with longer
survival (p < 0.001), independent of tumour size, grade, stage [p = 0.033, hazard
ratio (HR) = 0.80 95 % CI = 0.64-0.98]. Similar associations were maintained in
ER+ tumours in univariate and multivariate analysis (p < 0.01) both in patients
with and without adjuvant endocrine or chemotherapy. AR mRNA expression showed
significant association with tumour grade, molecular subtypes, and longer 10 and
15 years survival in luminal BC. In the external validation cohorts, AR gene
expression data were associated with improved patients' outcome (p < 0.001, HR =
0.84, 95 % CI 0.79-0.90). AR is not only an independent prognostic factor in ER
positive luminal BC but is also expressed in ER-negative tumours. AR could act as
a molecular target in patients with ER-positive disease predicting response to
adjuvant therapy.
PMID- 27514396
TI - Vigorous physical activity and risk of breast cancer in the African American
breast cancer epidemiology and risk consortium.
AB - The relationship between physical activity and breast cancer risk has been
extensively studied among women of European descent, with most studies reporting
inverse associations. However, data on American women of African ancestry (AA)
and by tumor subtypes are sparse. Thus, we examined associations of vigorous
exercise and breast cancer risk overall, and by estrogen receptor (ER) status, in
the African American Breast Cancer Epidemiology and Risk Consortium. We pooled
data from four large studies on 2482 ER+ cases, 1374 ER- cases, and 16,959
controls. Multivariable logistic regression was used to compute odds ratios (OR)
and 95 % confidence intervals (CI) for the risk of breast cancer overall, and
polytomous logistic regression was used to model the risk of ER+ and ER- cancer.
Recent vigorous exercise was associated with a statistically significant,
modestly decreased risk for breast cancer overall (OR 0.88, 95 % CI 0.81-0.96)
and for ER+ cancer (OR 0.88, 95 % CI 0.80-0.98), but not for ER- cancer (OR 0.93,
95 % CI 0.82-1.06). Overall, there was no strong evidence of effect modification
by age, menopausal status, body mass index, and parity. However, our data were
suggestive of modification by family history, such that an inverse association
was present among women without a family history but not among those with a
relative affected by breast cancer. Results from this large pooled analysis
provide evidence that vigorous physical activity is associated with a modestly
reduced risk of breast cancer in AA women, specifically ER+ cancer.
PMID- 27514398
TI - Corrigendum.
PMID- 27514397
TI - Adjuvant systemic therapy in early breast cancer: impact of guideline changes and
clinicopathological factors associated with nonadherence at a nation-wide level.
AB - Over recent years, adjuvant systemic treatment guidelines (AST) for early-stage
breast cancer have changed considerably. We aimed to assess the impact of these
guideline changes on the administration of AST in early-stage breast cancer
patients and to what extent these guidelines are adhered to at a nation-wide
level. We used Netherlands Cancer Registry data to describe trends in AST
prescription, adherence to AST guidelines, and to identify clinicopathological
determinants of nonadherence. Between 1990 and 2012, 231,648 Dutch patients were
diagnosed with early breast cancer, of whom 124,472 received AST. Adjuvant
endocrine treatment (ET) use increased from 23 % of patients (1990) to 56 %
(2012), and chemotherapy from 11 to 44 %. In 2009-2012, 8 % of patients received
ET and 3 % received chemotherapy without guideline indication. Conversely, 10-29
% of patients did not receive ET and chemotherapy, respectively, despite a
guideline indication. Unfavorable clinicopathological characteristics generally
decreased the chance of undertreatment and increased the chance for
overtreatment. Remarkable was the increased chance of ET undertreatment in
younger women (RR < 35 vs 60-69 years 1.79; 95 % CI 1.30-2.47) and in women with
HER2+ disease (RR 1.64; 95 % CI 1.46-1.85). Over the years, AST guidelines
expanded resulting in much more Dutch early breast cancer patients receiving AST.
In the majority of cases, AST administration was guideline concordant, but the
high frequency of chemotherapy undertreatment in some subgroups suggests limited
AST guideline support in these patients.
PMID- 27514399
TI - Landscape of Research on Older Adults' Health in the Arab Region: Is It
Demography-Driven or Development-Dependent?
AB - Objectives: To describe the quantity, methods, themes, and collaboration profiles
of research on older adults' health in the Arab world, and map research
productivity against demographic, economic, and development indicators. Methods:
A scoping review of research on older adults' health drawing from 7 databases and
covering the period 1994-2013. Results: Aging research output has increased 6
fold over the study period, with middle-income countries showing the sharpest
rise. The majority of the reviewed publications are descriptive in nature,
oriented toward examining the extent of disease or factors associated with
various morbidity and mortality outcomes (88.5%). Despite the increasing regional
instability, there is a dearth of studies on "seniors in emergencies."
Collaboration with international coauthors (16.0%) has been more frequent than
with regional coauthors (4.2%). Correlation analysis suggests that research
production has been more strongly influenced by literacy rates than by population
aging indicators, Gross Domestic Product, or government investment in research
and development. Discussion: This study lays the basis for a "roadmap" for
research on older adults' health in the Arab region. It calls for cooperation
among various stakeholders to produce a targeted and well-informed research
agenda that is more responsive to emerging and context-specific needs of older
adults in the region.
PMID- 27514400
TI - The state of ethical-legal oaths in UK medical practice today: Is it time to look
at standardising?
AB - The taking of an ethical-legal oath is a "rite of passage" for many medical
practitioners. A 1997 paper noted that half of medical schools in the UK
administer an oath. I performed a survey of UK medical schools to see whether
these are still used today. An electronic survey was sent to 31 UK medical
schools, asking them whether the Hippocratic Oath (in any version) was taken by
their medical students; non-respondents were followed up by telephone.
Information was obtained from 21 UK medical schools, giving a response rate of
68% (21/31). A total of 18 (86%) institutions use an oath. Ethical-legal oaths
are therefore taken in the vast majority of UK medical schools today. However, a
great variety are used, and there are advantages in standardisation. My
recommendation is that the Standard Medical Oath of the UK (SMOUK) is adopted by
all medical schools, and that this is also taken regularly by doctors as part of
revalidation.
PMID- 27514401
TI - Benign male genital dermatoses.
PMID- 27514402
TI - Ageless beauty.
PMID- 27514403
TI - Improving value-add work and satisfaction in medical residents training: a
resident-led quality improvement project employing the lean method to improve
hospital supply usage.
AB - PURPOSE: Our hospital has a Housestaff Quality Council that fosters education and
mentorship of medical residents for quality improvement methodologies. Medical
residents on our council identified non-standardised storage rooms as a source of
medical resident inefficiency and dissatisfaction. To improve value-add work,
medical residents implemented and evaluated a quality improvement project of
storage room supplies using the lean method. METHODS: Using 5S principle and lean
methodology, we designed and implemented a standardised supply cart with
physician specific supplies. Between April 2014 and April 2015, 40 random
observations (20 residents and 20 nurses) both before and after the standardised
supply cart implementation were made. The duration time to locate an item was
measured in seconds. The paths taken to locate items were drawn as spaghetti
diagrams. Nurses served as our control group given that their supplies were not
moved in the implementation. Fifty residents were surveyed to assess their
satisfaction. RESULTS: Implementation of the standardised supply cart reduced the
time for residents to locate an item per visit from 50.8 to 30.2 s in one unit
(p<0.05) and 127 to 28.3 s in the second unit (p<0.05). Mean time savings per day
per resident were 5 min. The spaghetti diagrams indicated that finding supplies
became more efficient after the intervention for residents. After the
intervention, 92% of residents reported finding supplies more rapidly and 86%
reported less frustration with finding supplies. CONCLUSIONS: Residents applied
the 5S principles and lean methodology to identify and solve a problem that
created inefficiency and dissatisfaction.
PMID- 27514404
TI - Do early internalizing and externalizing problems predict later irritability in
adolescents with attention-deficit/hyperactivity disorder?
AB - OBJECTIVE: Irritable mood is common in children with attention
deficit/hyperactivity disorder. Research to date has primarily comprised cross
sectional studies; thus, little is known about the antecedents of irritability.
Furthermore, existing cross-sectional studies generally focus on the association
between irritability and comorbidities and do not examine broader aspects of
functioning. Finally, previous research has neglected to include child-report of
irritability. This study aimed to address these gaps using data from a
longitudinal study of children with attention-deficit/hyperactivity disorder.
METHOD: Children aged 5-13 years (mean = 10.2; standard deviation = 1.9) with
attention-deficit/hyperactivity disorder were recruited from pediatric practices
across Victoria, Australia. This study reports on those who had reached
adolescence (12 years or older, mean = 13.8; standard deviation = 1.2) at the 3
year follow-up ( n = 140). Internalizing and externalizing problems were measured
using the Strengths and Difficulties Questionnaire. At follow-up, parent-reported
and adolescent self-reported irritability was assessed using the Affective
Reactivity Index. Parent and adolescent outcomes measured at follow-up included
attention-deficit/hyperactivity disorder symptom severity, sleep, behavior and
parent mental health. RESULTS: Children with externalizing problems at age 10 had
higher parent-reported irritability (beta = 0.31, 95% confidence interval =
[0.17,-0.45], p = 0.001) in adolescence. Cross-sectional analyses found that
irritability was associated with increased attention-deficit/hyperactivity
disorder symptom severity and sleep problems; poorer emotional, behavioral and
social functioning; and poorer parent mental health. CONCLUSION: Our findings
highlight the importance of assessing for and managing early conduct problems in
children with attention-deficit/hyperactivity disorder, as these predict ongoing
irritability which, in turn, is associated with poorer functioning across a
number of domains.
PMID- 27514405
TI - Systematic review of interventions for Indigenous adults with mental and
substance use disorders in Australia, Canada, New Zealand and the United States.
AB - OBJECTIVE: The aim of this study was to systematically review the evidence-base
for the effectiveness of culturally unadapted, culturally adapted and culture
based interventions for Indigenous adults with mental or substance use disorders.
METHODS: We conducted a systematic search of scientific databases, government
websites and web-based Indigenous research repositories. We sought studies using
designs comparing an intervention group to a control/comparator group or pre- and
post-test designs, published between 2000 and 2015 examining interventions to
improve individual-level outcomes (e.g. remission, symptoms, quality of life,
functioning) or service-level outcomes (e.g. number of interventions delivered)
for Indigenous adults with mental or substance use disorders in Australia,
Canada, New Zealand or the United States. RESULTS: A total of 16 studies met
inclusion criteria. Virtually all North American studies (6 US and 1 Canadian)
evaluated culturally unadapted interventions, all of which were interventions for
substance use. Two-thirds of Australian and New Zealand studies evaluated
culturally adapted interventions and included samples with mental disorders. Of
eight culturally unadapted psychological/psychosocial, pharmacological and
educational intervention studies, seven reported significant improvements on at
least one measure of psychological well-being, mental health problem severity, or
significantly reduced alcohol or illicit drug use. Of seven culturally adapted
psychological/psychosocial intervention studies, all reported significant
improvement on at least one measure of symptoms of mental illness, functioning,
and alcohol use. One culture-based psychological/psychosocial intervention study
significantly reduced problem severity in medical and psychiatric domains.
CONCLUSION: There remains inconclusive evidence regarding interventions due to a
small and methodologically weak evidence-base. The literature would be enhanced
by intervention replication and outcome standardisation, validating the outcome
instruments used in Indigenous populations, including sample size calculations
and using stronger research designs (e.g. interrupted time-series designs).
Robust implementation and outcomes research is needed to further progress
evidence-based practice in Indigenous mental health.
PMID- 27514408
TI - [Performance evaluation of two N95 filtering-facepiece respirators on
decomposition products of sulfur hexafluoride].
AB - OBJECTIVE: To assess the filtration efficiency of two N95 filtering-facepiece
respirators (FFRs) for the decomposition products of sulfur hexafluoride (SF6).
METHODS: Two types of N95 FFRs (the particulate and the acid-proof respirators)
were selected in this study. The decomposition products of SF6, including
particles, hydrogen fluoride (HF) and sulfur dioxide (SO2) , were measured under
experimental condition by using TSI PortaCount Plus, fluorine ion-selective
electrodes and spectrophotometer separately. The filtration efficiency was then
calculated and compared. RESULTS: Both two models of N95 respirators had lowest
filtration efficiency larger than 95% for particles under airflow ranged from 10
to 95 L/min. When exposed to different concentrations of HF (low: 0.00~1.99
mg/m(3), middle: 2.00~3.99 mg/m(3), high: >4 mg/m(3)) , the acid-proof N95
respirator was more effective than the particulate respirator (P<0.05) with a
filtration efficiency of 98.83%, 99.08%, and 99.03% versus 48.44%, 45.71%, and
47.31%. For four SO2 concentration ranges (0.00~2.49 mg/m(3), 2.50~4.99 mg/m(3),
5.00~9.99 mg/m(3), and >10.00 mg/m(3)) , the acid-proof respirator showed a high
filtration efficiency within exposure to 1.5 hours: 95.73%, 98.67%, 98.14%, and
97.78%, respectively, when exposure duration extended to 4 hours, the filtration
efficiency of the acid-proof respirator decreased to 91.97%, 82.28%, 70.12%, and
58.56%, respectively. CONCLUSION: Both the particulate and the acid-proof N95
FFRs met national standards on the particulate filtration efficiency. The acid
proof N95 respirator demonstrates to be more effective in filtering HF and SO2
than the particulate respirator. The filtration efficiency could decrease to an
unsafe condition under longer exposure duration, timely replacement of respirator
is recommended at the workplace.
PMID- 27514407
TI - Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to
Confer Increased Bladder Cancer Risk.
AB - : It is well established that environmental toxins, such as exposure to arsenic,
are risk factors in the development of urinary bladder cancer, yet recent genome
wide association studies (GWAS) provide compelling evidence that there is a
strong genetic component associated with disease predisposition. A single
nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12,
residing 6 kb upstream of the important cell-cycle regulator and proto-oncogene,
Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer
predisposition has been unclear because it lies within a non-coding region of the
genome. Here, it is demonstrated that bladder cancer cells heterozygous for this
SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription
occurring from the risk allele. Furthermore, using chromatin immunoprecipitation
assays, a novel enhancer element was identified within the first intron of CCNE1
that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in
bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP
in high-linkage disequilibrium with rs8102137 residing in the center of a KLF5
motif, alters KLF5 binding to this genomic region. Through luciferase assays and
CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element
controlling CCNE1 transcription is characterized. These studies uncover how a
cancer-associated polymorphism mechanistically contributes to an increased
predisposition for bladder cancer development. IMPLICATIONS: A polymorphic KLF5
binding site near the CCNE1 gene explains genetic risk identified through GWAS.
Mol Cancer Res; 14(11); 1078-86. (c)2016 AACR.
PMID- 27514409
TI - [Benzoquinone induce autophagy in HL60 cells and the role of reactive oxygen
species in induced autophagy].
AB - OBJECTIVE: To investigate whether autophagy can be induced by 1, 4-benzoquinone
(1, 4-BQ) in HL60 cells, as well as the role of reactive oxygen species (ROS) in
induced autophagy. METHODS: In order to determine a suitable 1, 4-BQ treatment
concentration for autophagy detection in HL60 cells, the cell vitality were
examined by CCK8 assay. Logarithmic-growth-phased cells were divided into control
group, 1, 4-BQ group (10MUmol/L 1, 4-BQ, 24 h) , NAC group (antioxidant n-acetyl
cysteine, 5mmol/L, 24 h) and the 1, 4-BQ+NAC group (5 mmol/L NAC were
preincubated for 1h prior to the treatment with 10 MUmol/L 1, 4-BQ for 24 h). The
autophagic acidic vesicle were inspected by acridine orange staining, LC3 were
detected by immunofluorescence staining, and expressions of LC3 and Beclin1 were
quantitatively detected by Western blot. RESULTS: The results from cell viability
test indicated that 1, 4-BQ exhibited a dose-dependent toxicity to HL60 cells.
Compared with control group.the cell viability in 20.0,40.0MUmol/L concentration
were decreased obviously, and the differences had statistical significance
(P<0.05). Compare with contrd group acidic vesicle, LC3II, LC3II/LC3I and Beclin1
protein expressions were increased in 1, 4-BQ group, after both respectively
12.4% and 27%, the differences had statistital significance. While 1, 4-BQ+NAC
group was observed that acidic vesicle, LC3 and Beclin1 protein level were
markedly lower than 1, 4-BQ group, after both decreased 12.6% and 22.6%
respectively, both the difference were statistically significant (P<0.05).
CONCLUSION: 1, 4-BQ can induce autophagy in HL60 cells, the induction of
autophagy is at least partly resulted from ROS. Antioxidant can effectively
suppress the occurrence of induced autophagy.
PMID- 27514406
TI - Ercc1 Deficiency Promotes Tumorigenesis and Increases Cisplatin Sensitivity in a
Tp53 Context-Specific Manner.
AB - : KRAS-mutant lung adenocarcinoma is among the most common cancer entities and,
in advanced stages, typically displays poor prognosis due to acquired resistance
against chemotherapy, which is still largely based on cisplatin-containing
combination regimens. Mechanisms of cisplatin resistance have been extensively
investigated, and ERCC1 has emerged as a key player due to its central role in
the repair of cisplatin-induced DNA lesions. However, clinical data have not
unequivocally confirmed ERCC1 status as a predictor of the response to cisplatin
treatment. Therefore, we employed an autochthonous mouse model of Kras-driven
lung adenocarcinoma resembling human lung adenocarcinoma to investigate the role
of Ercc1 in the response to cisplatin treatment. Our data show that Ercc1
deficiency in Tp53-deficient murine lung adenocarcinoma induces a more aggressive
tumor phenotype that displays enhanced sensitivity to cisplatin treatment.
Furthermore, tumors that relapsed after cisplatin treatment in our model develop
a robust etoposide sensitivity that is independent of the Ercc1 status and
depends solely on previous cisplatin exposure. Our results provide a solid
rationale for further investigation of the possibility of preselection of lung
adenocarcinoma patients according to the functional ERCC1- and mutational TP53
status, where functionally ERCC1-incompetent patients might benefit from
sequential cisplatin and etoposide chemotherapy. IMPLICATIONS: This study
provides a solid rationale for the stratification of lung adenocarcinoma patients
according to the functional ERCC1- and mutational TP53 status, where functionally
ERCC1-incompetent patients could benefit from sequential cisplatin and etoposide
chemotherapy. Mol Cancer Res; 14(11); 1110-23. (c)2016 AACR.
PMID- 27514410
TI - [Effects of malathion on testicular enzyme activities and sperm quality of male
rats].
AB - OBJECTIVE: The aim of this study is to investigate the effects of sub chronic
exposure to malathion on testicular enzyme activities and sperm quality of male
rats. METHODS: Forty male rats were divided into four groups: three exposure
groups and a control group. Malathion was administered orally to male rats at 0,
33.75, 54.00, and 108.00 mg/kg for 60 days to evaluate the toxic alterations in
sperm dynamics and testicular enzyme activities including ACP,LDH,SDH and gamma
GT. The control rats were administered with an equivalent volume of distilled
water in the same manner.After sacrificed, the testes were collected and weighed.
RESULTS: The body weight and the testis weight of animals showed a decreasing
tendency, and there was a statistical difference between the 54.00, 108.00 mg/kg
groups, and the control group (P<0.05). Malathion brought about marked reduction
in testicular sperm counts, sperm motility, and significant growth of sperm
malformation rate in 108.00 mg/kg group. A significant decrease in the activities
of testicular enzyme ACP and gamma-GT was observed in malathion exposed rats,
while the activities of LDH was significant increased and there were no obvious
effects on the activities of SDH. The activities of ACP, gamma-GT and LDH showed
a statistical difference between the 108.00 mg/kg groups, and the control group.
CONCLUSION: Malathion reduced the sperm counts and sperm motility, increased the
malformation rate and reduced the activities of testicular enzymies of male rats.
PMID- 27514411
TI - [Clinical value of serum presepsin (SCD14-ST) concentration measurement in
patients with pesticide poisoning].
AB - OBJECTIVE: To investigate the value of serum presepsin concentration measurement
in the clinical diagnosis and treatment of patients with pesticide poisoning
patients. METHODS: A total of 160 patients with pesticide poisoning were enrolled
as study subjects and divided into moderate organophosphate pesticide poisoning
group (40 patients) , severe organophosphate pesticide poisoning group (40
patients) , abamectin pesticide poisoning group (40 patients) , and paraquat
poisoning group (40 patients). A total of 20 healthy volunteers were enrolled as
the control group. All the patients with poisoning received conventional
treatment of pesticide poisoning immediately after admission, and serum presepsin
concentration was measured on days 1 (within 24 hours after poisoning) , 3, and 7
of admission, and biochemical and radiological parameters related to the
patient's condition were also examined. The patients with a Presepsin
concentration of >800 pg/ml on day 1 of admission were randomly divided into
conventional treatment group and ulinastatin treatment group, and the treatment
outcome was compared between the two groups. RESULTS: Compared with the healthy
control group, the groups with pesticide poisoning showed significant increases
in serum Presepsin concentrations, with the highest degree of increase on day 1
(P <0.05). The serum Presepsin concentration was positively correlated with
alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine
kinase MB, lactate dehydrogenase, serum creatinine, blood urea nitrogen,
interleukin-18, and white blood cell count, but negatively correlated with
cholinesterase. In the conventional treatment group and ulinastatin treatment
group, the overall response rate was 68% and 78.8%, respectively, with a
significant difference between the two groups (P<0.05). In 40 patients with
paraquat poisoning, 32 experienced an increase in serum presepsin concentration,
and among these 32 patients, 27 (83%) experienced exudation on lung CT.
CONCLUSION: Serum Presepsin concentration measurement can assist early diagnosis,
evaluation of disease severity, and guidance for clinical medication in patients
with pesticide poisoning, especially in those with severe pesticide poisoning and
a tendency to multiple organ failure.
PMID- 27514412
TI - [Effect and mechanism of interleukin-8 expression induced by wood smoke particles
in primary human airway epithelial cells].
AB - OBJECTIVE: To investigate the effect and mechanism of interleukin-8 expression
induced by wood smoke particles (WSP) in primary human airway epithelial cells.
METHODS: Primary human bronchial epithelial cells (HBEC) were collected through
fiberbronchoscopic brushing and incubated with different concentration of WSP (0,
12.5, 25.0, 50.0, 100.0 MUg/ml). Levels of IL-8 protein in cell culture
supernatant were measured using enzyme-linked immune sorbent assay. The specific
inhibitors for epidermal growth factor receptor (EGFR) and p38 kinase signaling
pathways were employed to pretreat HBEC, respectively, prior to incubation with
100 MUg/ml WSP to investigate the mechanism of IL-8 expression induced by WSP.
RESULTS: The expression of IL-8 was significant increased in a dose-dependent
manner after exposure HBEC to different concentration of WSP for 24h. The levels
of IL-8 expression were (4546.67+/-1421.42) rhog/ml in (PD153035+WSP) group and
(2803.33+/-865.00) rhog/ml in (SB203580+WSP) group respectively, which were
significant decreased compared with the level of (12896.67+/-1373.11) rhog/ml in
WSP group (P<0.05). CONCLUSION: WSP could induce IL-8 expression by means of EGFR
and p38 signaling pathways.
PMID- 27514413
TI - [Blood cerebrospinal fluid barrier damage of rats induced by lead acetate or nano
lead exposure].
AB - OBJECTIVE: To investigate the damage of blood-cerebrospinal fluid barrier (BCB)
of rats induced by lead and nano-lead exposure in order to provide the basis for
mechanism study of lead neurotoxicity. METHODS: 39 male rats were randomly
divided into control group, lead acetate exposed group and nano-lead exposed
group. Rats in lead acetate exposed group and nano-lead exposed group were given
20 mg/kg lead acetate or nano-lead by oral gavage and rats in control groups were
given the same amount saline for 9 weeks.Morris maze was used to test the
learning function, serum albumin and CSF albumin were determined by ELISA.
Confocal laser scanning microscope was applied to detect ZO-1 and Occludin
protein expression in choroid plexus, real time-PCR was used to test the
expression of ZO-1 and Occludin mRNA expression. Pathological changes of choroid
plexus cells were observed by the electron microscopy. RESULTS: Compared with the
control group, the escape latency of rats in lead acetate or nano-lead exposure
group were longer and times of across platform were less. The levels of CSF
albumin and the CSF albumin index in lead acetate or nano-lead exposed rats were
obviously higher, and the fluorescence intensity of ZO-1, Occludin as well as
mRNA expressions were lower than those in control group(P<0.05). Compared with
lead acetate exposed group, the levels of CSF albumin and the CSF albumin index
in nano-lead exposure group were higher. The fluorescence intensity and mRNA
expressions of ZO-1, Occludin in nano-lead exposure group were than those in lead
acetate group(P<0.05). Electron microscopy revealed that lead acetate or nano
lead exposure could induce shorter microvillus of choroid plexus epithelial
cells, mitochondrion destruction and partial disconnection in intracellular
junctions between two adjacent epithelial cells. CONCLUSION: Lead acetate and
nano-lead exposed can result in the blood-cerebrospinal fluid barrier damage,
which may involve in the process of lead induced neurotoxicity. Meanwhile, nano
lead exposure can induced in more worse damage in terms of blood-results in blood
cerebrospinal fluid barrier function.
PMID- 27514414
TI - [Report on 11 cases occupational acute arsine poisoning].
PMID- 27514415
TI - [Effects of long term and low dose Di- (2-ethylhexyl) phthalate exposure on
global genome DNA methylation in HePG2 cells].
AB - OBJECTIVE: To explore the potential effects of long-term and low-dose Di- (2
ethylhexyl) phthalate (DEHP) exposure on whole genome DNA methylation status and
cytotoxicity of HePG2 cells. METHODS: HePG2 cells were exposed to 1.5,15.0 and
150.0 MUmol/L DEHP for 24 hours, after continuous exposure for 20 generations,
mRNA and protein expression level of DNA (cytosine-5) -methyltransferase 1 (DNMT
1) , whole genome DNA methylation, cell apoptosis levels and cell cycle were
determined in both DEHP exposed cells and control cells. RESULTS: After DEHP
exposure, the mRNA and protein expression levels of DNMT 1 were decreased
significantly (P<0.05 or P<0.01). The genome DNA methylation levels of HePG2
cells were down-regulated along with the increasing of DEHP exposure level (15.0,
150.0 MUmol/L, P<0.05 and P<0.01). In term of cell apoptosis rates, only the late
stage cell apoptosis rates of the highest DEHP dosage group (150.0 MUmol/L DEHP)
were observed to have a significant increase (P<0.05). There were no significant
alterations in term of cell cycle. CONCLUSION: After long term and low dose DEHP
exposure, the whole genome DNA methylation levels of HePG2 cells were down
regulated obviously, which might be one of the most important toxic mechanism of
DEHP to induce pathophysiologic changes. Meanwhile, a certain content of cell
apoptosis were observed in highest dosage group of DEHP exposure, which showed
cytotoxicty of DEHP. However, there are no significant effects of DEHP exposure
on cell cycles.
PMID- 27514416
TI - [Effects of forsythia suspense on the liver gene expression levels of rats with
sepsis model].
AB - OBJECTIVE: To study the effects of forsythia extract on the liver gene expression
levels of rats with sepsis model. METHODS: The 90 Wistar rats were randomly
divided into three groups: sham operation group (n=30) , sepsis model group
(n=30) and forsythia group (n=30). The survival rates at 48 h and 72 h were
observed for all groups. The sepsis model and forsythia group rats were prepared
by "CLP" method. 72 h later the rats were sacrificed by removed the vertebra.
Under sterile conditions,cut the size of about 10 mm*10 mm*3 mm rat liver tissue
and placed in liquid nitrogen for use. The same with the sham operation group.
The gene expression levels of livers in all groups were detected by the
Applications Rat Genome 230 2.0 microarray,and the relative strength of both the
fluorescence signal ratio>2 or <-2 screening significantly different genes, by
the US National Center for Biotechnology Information (NCBI) database query gene
function and classify. RESULTS: Forsythia group 48 h, 72 h rat mortality rates
were 30% and 50%, the sepsis model group 48 h, 72 h rat mortality rates were
46.7% and 70%, two groups 48 h, 72 h mortality rates were compared, the
differences were statistically significant (P<0.05). 72 hours after CLP, the
genes with up-regulation in sepsis model group/sham operation group and with down
regulation in Forsythia group/sepsis model group were 14. The genes with down
regulation in sepsis model group/sham operation group and with up-regulation in
Forsythia group/sepsis model group were 11. The genes involves immune-related
genes 8, metabolism genes 5, material transport two related genes, cell adhesion
two related genes, cell proliferation, differentiation and apoptosis related
genes 4, transcriptional regulation genes 2and other related gene. CONCLUSION:
Forsythia can reduce the 48, 72 h mortality of rats with sepsis and can regulate
abnormal sepsis liver genes which associated with tissue immunity, inflammation,
metabolism occur regression expression.
PMID- 27514417
TI - [An investigation on job burnout of medical personnel in a top three hospital].
AB - OBJECTIVE: To investigate job burnout status of medical Personnel in a top three
hospitals, in order to provide basic data for intervention of the hospital
management. METHODS: A total of 549 doctors and nurses were assessed by Maslach
Burnout Inventory-Human Service Survey (MBI-HSS). SPSS 19.0 software package was
applied to data description and analysis, including univariate analysis and
orderly classification Logistic regression analysis. RESULTS: The rate of high
job burnout of doctors and nurses are 36.3% and 42.8% respectively. Female
subjects got higher scores (29.4+/-13.5) on emotional exhaustion than male
subjects (26.2+/-12.8) compared with.Doctors got lower scores (28.2+/-15.9) on
emotional exhaustion and higher scores (31.4+/-9.3) on personal accomplishment
than nurses.Compared with subjects with higher professional title, young subjects
with primary professional title got lower scores on personal
accomplishment.Subjects with 11-20 years working age got the highest scores on
depersonalization.Among all the test departments, medical personnel of emergency
department got the highest scores (31.9+/-12.6) on emotional exhaustion,while the
lowest scores (28.1+/-8.0) on personal accomplishment. According to the results
of orderly classification Logistic regression analysis, age, job
type,professional qualifications and clinical departments type entered the
regression model. CONCLUSION: Physical resources and emotional resources of
medical personnel are overdraft so that they got some high degree of job
burnout.Much more attention should be paid to professional mental health of
nurses,and personnel who at low age,got low professional titles.Positive measures
should be provided, including management mechanism,organizational culture,
occupational protection and psychological intervention.
PMID- 27514418
TI - [Survival analysis of patients with pneumoconiosis from 1963 to 2014 in Yueyang].
AB - OBJECTIVE: To know the incidence and survival rate of patients with
pneumoconiosis in Yueyang and investigate the related factors of death hazard
ratio. METHODS: A total; of 1404 patients with pneumoconiosis were diagnosed and
reported from 1963.1-2014.12. Log Rank method and Cox regression model were used
to make the survival analysis. RESULTS: The case fatality rate of pneumoconiosis
was 24.57%,and rose with the increase of pneumoconiosis stage, the average course
of disease was (14.7+/-8.7) years, the average age of death was (60.6+/-11.3)
years, tuberculosis,Chronic cardiopulmonary disease and pneumonia were the top
three cause of death for patients. The survival rates which included three stages
of pneumoconiosis patients and the patients whether or not complicated with
tuberculosis were significant statistical differences. Cox regression analysis
revealed that the main impact. factors for the survival of patients with
pneumoconiosis and the value of. the death hazard ratios (RR) of above seven
factors were silicosis (2.28) ,the increase of pneumoconiosis stage (1.77)
,pneumoconiosis complicated with tuberculosis (1.29) ,the increase of stage
promotion (1.20) ,the increase of age of the first contacting dust (1.08) ,the
expansion of the scale of enterprise (0.55) and the later period of contacting
dust (0.37). CONCLUSION: Prevention of pneumoconiosis should focus on silicosis
in Yueyang, the prevention and treatment of pneumoconiosis complicated with
tuberculosis is an important means for improving the survival of patients.
PMID- 27514419
TI - [The immunological effects of phthalanilic acid on mice].
AB - OBJECTIVE: To explore the effects of phthalanilic acid on immune system in mice
from the respects of blood, tissues, cell and cytokines. And to find sensitive
index of immunological effects and offer experimental data for toxicological
safety evaluation. METHODS: 60 balb/c mice were randomly divided into 4 groups.
The mice in control group were given soybean oil. The mice in group 2 to 4 were
given phthalanilic acid at dose 30 mg/kg, 100 mg/kg and 300 mg/kg by gavage
respectively for 28 days. After 24 hours of the last contamination, the
histopathology of spleen and thymus, immunologic factors and cell multiplication
of lymphocyte were analysed. The data were analysed by SPSS. RESULTS: After
contamination for 28 days, 300 mg/kg phthalanilic acid could cause that the cell
multiplication of lymphocyte were inhibited. Spleens were damaged at the dose of
100 mg/kg. The concentration of IFN-gamma and IL-4[ (843.31+/-14.81) pg/ml and
(1174.44+/-7.32) pg/ml] in thymus were increased significantly (P<0.05) at the
dose of 30 mg/kg. CONCLUSION: Different doses of phthalanilic acid may damnify
the immune system of mice at different degrees for 28 days continuous
contamination. Phthalanilic acid might have immunotoxicity.
PMID- 27514420
TI - [Clinical analysis on 473 cases of occupational acute acrylonitrile poisoning].
PMID- 27514421
TI - [Emergency management of 9 patients with acute aconite poisoning].
PMID- 27514422
TI - [A case report of hands tremor caused by organophosphorus and cypermethrin mixed
pesticide poisoning].
PMID- 27514423
TI - [Analysis on influencing factors of prognosis of patients with acute
organophosphorus pesticide poisoning].
AB - OBJECTIVE: To analyze the relationship between risk factors and prognosis of
acute organophosphorus pesticide poisoning (AOPP). METHODS: The clinical data
including APACHEII, D-dimer, C-reactive protein, procalcitonin, lactic acid of
the 67 cases of acute organophosphorus pesticide poisoning which respectively
divided into survival group and death group by the outcome were collected. The
independent influcing factors were got by logistic regression analysis. RESULTS:
The analysis showed that APACHEII, D-dimer,C-reactive protein and Procalcitonin
were influencing factors to evaluate prognosis of AOPP (P<0.05) .Meanwhile,
APACHEII and CRP were the independent influencing factors to evaluate prognosis
of AOPP (P<0.05). APACHEII26was the optimum thresholds to acess the prognosis of
AOPP and its Youden index was largest. CONCLUSION: APACHEII and CRP played an
important role in the assessment of prognosis on AOPP. When APACHEIIwas more than
26, it suggested the patient of AOPP will have a bad prognosis.
PMID- 27514424
TI - [Impact of coal workers' pneumoconiosis complicated by lymph node fibrosis in
lung cancer on surgical treatment].
AB - OBJECTIVE: To investigate the impact of coal workers' pneumoconiosis complicated
by the pathological changes in lymph nodes in lung cancer on surgical treatment.
METHODS: A total of 63 patients with non-small cell lung cancer who received
pulmonary lobectomy and systemic mediastinal lymph node dissection were enrolled
and divided into the group with coal workers' pneumoconiosis complicated by lung
cancer (30 patients) and the non-pneumoconiosis liver cancer group (33 patients).
The short-term outcome was compared between the two groups and confirmed by lymph
node fibrosis shown by postoperative pathological examination. The predictive
value of lymphadenectasis on chest CT was analyzed. RESULTS: Compared with the
non-pneumoconiosis liver cancer group, the group with coal workers'
pneumoconiosis complicated by lung cancer had significant increases in time of
operation, intraoperative blood loss, postoperative extubation time, and length
of hospital stay (P<0.05). The patients were divided into groups according to the
presence or absence of lymph node fibrosis, and the group with lymph node
fibrosis had a significantly longer time of operation and greater intraoperative
blood loss than the group without lymph node fibrosis (P<0.05). CONCLUSION: When
coal workers' pneumoconiosis is complicated by lung cancer, severe lymph node
fibrosis often causes difficulties in surgery, and thoracotomy may be a safe and
effective therapeutic method.
PMID- 27514425
TI - [An inhalation poison caused by thermal degradation products of fluorine
polymer].
PMID- 27514426
TI - [A case of mis-intravenous injection of thinner poisning].
PMID- 27514427
TI - [A case of acute carbon monoxide poisoning with pancreatitis as the prominent
dinical manifestation].
PMID- 27514429
TI - [A case report of hemoperfusion treat kidney damage caused eating fish gall
bladder poisoning].
PMID- 27514428
TI - [Analysis of hemoperfusion in the treatment of thinner poisoning effect].
AB - OBJECTIVE: To investigate the combination of drugs in blood perfusion-based
rescue therapy of acute poisoning thinners. METHODS: Our department were
retrospectively analyzed in May 2011 to October 2014, 54 cases thinners poisoning
patients choose the thinner should be 44 cases of acute poisoning patients were
divided into two groups. Toluene, xylene group 8 cases; Halogenated hydrocarbon
group 34cases; Give blood perfusion 3 to 7 times, compared before and after the
blood perfusion of toxicant concentration, results and biochemical indicators.
RESULTS: By selection of 44 patients with acute thinners poisoning in 42 patients
were successfully treated, the cure rate was 96%. And treatment in patients with
successful both in toluene, xylene, or halogenated hydrocarbon group after blood
perfusion its toxicant concentration significantly decreased; 42 patients blood
perfusion treatment of the indexes of liver function after than before treatment
significantly improved. CONCLUSION: The early hemoperfusion is a very effective
way of acute poisoning thinners currently rescue.
PMID- 27514430
TI - [Determination of trace cobalt in human urine by graphite furnace atomic
absorption spectrometr].
AB - OBJECTIVE: To establish a method to determine cobalt in human urine by graphite
furnace atomic absorption spectrometry. METHODS: Urine with 2% nitric acid
diluted two-fold, to quantify the curve, graphite furnace atomic absorption
spectrometric detection. RESULTS: Co was linear within 2.5~40.0 ng/ml with
r>0.999. Spike experiment showed that Co received good recovery rate, which was
90.8%~94.8%. Intra-assay precisions were 3.2%~5.1% for Co, inter-assay precisions
were 4.4%~5.2% for Co. CONCLUSION: The method by using graphite furnace atomic
absorption spectrometr to determine urine Co was fast, accurate and with low
matrix effect. It could meet the requirement in GBZ/T 210.5-2008.
PMID- 27514431
TI - [Determination of trace cobalt and tungsten in human urine by inductively coupled
plasma mass spectrometry].
AB - OBJECTIVE: To establish a method to determine cobalt and tungsten in human urine
by ICP-MS. METHODS: Both Co and W were linear within 0.05~10.00 ng/ml with
r>0.999. Spike experiment showed that both Co and W received good recovery rate,
which were 90%~97%. Intra-assay precisions were 3.2%~5.1% for Co and 2.2%~4.1%
for W, inter-assay precisions were 4.4%~5.2% for Co and 3.7%~4.5% for W. RESULTS:
CONCLUSION: The method by using ICP-MS to determine urine Co and W was fast,
accurate and with low matrix effect. It could meet the requirement in GBZ/T 210.5
2008.
PMID- 27514432
TI - [Monitoring and clinical treatment of naphthalene poisoning].
PMID- 27514433
TI - [Progress on predictors of patients with acute paraquat poisoning].
PMID- 27514434
TI - [Diagnosis and research progress of occupational asthma].
PMID- 27514435
TI - A Molecular Tetrapod for Organic Photovoltaics.
AB - The synthesis and characterization of a molecular tetrapod, SFBTD, featuring a
tetraphenylsilane center and four identical conjugated arms, which structurally
resembles breakwaters in common wave-reducing shore constructions, are reported.
Cyclic voltammetry reveals that SFBTD has a medium band gap of ca. 2.0 eV and a
low-lying HOMO energy level at ca. -5.2 eV. Absorption spectroscopy, X-ray
diffraction, and differential scanning calorimetry experiments reveal a low
degree of crystallinity in this compound and slow crystallization kinetics. Bulk
heterojunction organic photovoltaics (OPVs) employing SFBTD and fullerene
derivatives exhibit power conversion efficiencies (PCEs) up to 1.05% and open
circuit voltage (VOC) values as high as 1.02 V. To the best of our knowledge,
this is the highest PCE obtained for OPVs employing molecular tetrapods as donor
materials. These devices are relatively thermally stable due to the known ability
of breakwater tetrapods to interlock, preventing dislodging and sliding. The lack
of favorable phase separations and low hole mobilities of the blend films are the
major factors limiting the device performance. Ternary blend devices by the
addition of three low band gap poly(thienylene vinylene) (PTV) derivatives were
fabricated and tested. We found that the added PTVs acted to be either the major
hole conductor or a competing hole conduction channel depending on the HOMO level
positions relative to that of SFBTD. Some of the ternary OPV devices out
performed the corresponding binary counterparts employing SFBTD or PTVs alone,
suggesting cooperative effects in the ternary systems.
PMID- 27514436
TI - Development of a simultaneous optical/PET imaging system for awake mice.
AB - Simultaneous measurements of multiple physiological parameters are essential for
the study of brain disease mechanisms and the development of suitable therapies
to treat them. In this study, we developed a measurement system for simultaneous
optical imaging and PET for awake mice. The key elements of this system are the
OpenPET, optical imaging and fixation apparatus for an awake mouse. The OpenPET
is our original open-type PET geometry, which can be used in combination with
another device because of the easily accessible open space of the former. A small
prototype of the axial shift single-ring OpenPET was used. The objective lens for
optical imaging with a mounted charge-coupled device camera was placed inside the
open space of the AS-SROP. Our original fixation apparatus to hold an awake mouse
was also applied. As a first application of this system, simultaneous
measurements of cerebral blood flow (CBF) by laser speckle imaging (LSI) and
[(11)C]raclopride-PET were performed under control and 5% CO2 inhalation
(hypercapnia) conditions. Our system successfully obtained the CBF and
[(11)C]raclopride radioactivity concentration simultaneously. Accumulation of
[(11)C]raclopride was observed in the striatum where the density of dopamine D2
receptors is high. LSI measurements could be stably performed for more than 60
minutes. Increased CBF induced by hypercapnia was observed while CBF under the
control condition was stable. We concluded that our imaging system should be
useful for investigating the mechanisms of brain diseases in awake animal models.
PMID- 27514437
TI - Methodological reporting quality of randomized controlled trials: A survey of
seven core journals of orthopaedics from Mainland China over 5 years following
the CONSORT statement.
AB - BACKGROUND: In recent years, the number of randomized controlled trials (RCTs) in
the field of orthopaedics is increasing in Mainland China. However, randomized
controlled trials (RCTs) are inclined to bias if they lack methodological
quality. Therefore, we performed a survey of RCT to assess: (1) What about the
quality of RCTs in the field of orthopedics in Mainland China? (2) Whether there
is difference between the core journals of the Chinese department of orthopedics
and Orthopaedics Traumatology Surgery & Research (OTSR). MATERIAL AND METHODS:
This research aimed to evaluate the methodological reporting quality according to
the CONSORT statement of randomized controlled trials (RCTs) in seven key
orthopaedic journals published in Mainland China over 5 years from 2010 to 2014.
All of the articles were hand researched on Chongqing VIP database between 2010
and 2014. Studies were considered eligible if the words "random", "randomly",
"randomization", "randomized" were employed to describe the allocation way.
Trials including animals, cadavers, trials published as abstracts and case
report, trials dealing with subgroups analysis, or trials without the outcomes
were excluded. In addition, eight articles selected from Orthopaedics
Traumatology Surgery & Research (OTSR) between 2010 and 2014 were included in
this study for comparison. The identified RCTs are analyzed using a modified
version of the Consolidated Standards of Reporting Trials (CONSORT), including
the sample size calculation, allocation sequence generation, allocation
concealment, blinding and handling of dropouts. RESULTS: A total of 222 RCTs were
identified in seven core orthopaedic journals. No trials reported adequate sample
size calculation, 74 (33.4%) reported adequate allocation generation, 8 (3.7%)
trials reported adequate allocation concealment, 18 (8.1%) trials reported
adequate blinding and 16 (7.2%) trials reported handling of dropouts. In OTSR, 1
(12.5%) trial reported adequate sample size calculation, 4 (50.0%) reported
adequate allocation generation, 1 (12.5%) trials reported adequate allocation
concealment, 2 (25.0%) trials reported adequate blinding and 5 (62.5%) trials
reported handling of dropouts. There were statistical differences as for sample
size calculation and handling of dropouts between papers from Mainland China and
OTSR (P<0.05). CONCLUSION: The findings of this study show that the
methodological reporting quality of RCTs in seven core orthopaedic journals from
the Mainland China is far from satisfaction and it needs to further improve to
keep up with the standards of the CONSORT statement. LEVEL OF EVIDENCE: Level III
case control.
PMID- 27514438
TI - Fibroblast growth factor and vascular endothelial growth factor play a critical
role in endotheliogenesis from human adipose-derived stem cells.
AB - OBJECTIVE: Adipose-derived stem cells (ASCs) are a potential adult mesenchymal
stem cell source for restoring endothelial function in patients with critical
limb ischemia. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth
factor (VEGF) play a major role in angiogenesis and wound healing. This study
evaluated the effects of FGF and VEGF on the proliferation, migration, and
potential endothelial differentiation of human ASCs with regards to their use as
endothelial cell substitutes. METHODS: ASCs were isolated from clinical
lipoaspirates and cultured in M199 medium with fetal bovine serum (10%), FGF2 (10
ng/mL), VEGF (50 ng/mL), or combinations of FGF2 and VEGF. Cell proliferation
rates, viability, and migration were measured by growth curves, MTT (3-(4,5
dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and scratch assays. For
cell attachment determinations, ASCs were seeded onto a scaffold of small
intestinal submucosa for 5 days. Endothelial differentiation capabilities of ASCs
were confirmed by expression of endothelial cell-specific markers using
quantitative polymerase chain reaction, immunofluorescence staining, and cord
formation on Matrigel (BD Biosciences, San Jose, Calif). PD173074, a selective
inhibitor of FGF receptor, was used to confirm the importance of FGF signaling.
RESULTS: ASCs treated with FGF or combinations of FGF and VEGF showed increased
proliferation rates and consistent differentiation toward an endothelial cell
lineage increase in platelet endothelial cell adhesion molecule (CD31), von
Willebrand factor, endothelial nitric oxide synthase, and vascular endothelial
cadherin message, and in protein and cord formation on Matrigel. FGF and VEGF
stimulated ASC migration and increased the attachment and retention after seeding
onto a matrix graft of small intestinal submucosa. Blockade of FGF signaling with
PD173074 abrogated ASC endothelial cell differentiation potential. CONCLUSIONS:
These results indicate that FGF and VEGF are ASC promoters for proliferation,
migration, attachment, and endothelial differentiation. FGF and VEGF have a
costimulatory effect on ASC endotheliogenesis. These results further suggest that
ASCs with enhanced FGF signaling may potentially be used for tissue engineering
and cell-based therapies in patients with critical limb ischemia.
PMID- 27514439
TI - The role of passive sampling in monitoring the environmental impacts of produced
water discharges from the Norwegian oil and gas industry.
AB - Stringent and periodic iteration of regulations related to the monitoring of
chemical releases from the offshore oil and gas industry requires the use of ever
changing, rapidly developing and technologically advancing techniques. Passive
samplers play an important role in water column monitoring of produced water (PW)
discharge to seawater under Norwegian regulation, where they are used to; i)
measure aqueous concentrations of pollutants, ii) quantify the exposure of caged
organisms and investigate PW dispersal, and iii) validate dispersal models. This
article summarises current Norwegian water column monitoring practice and
identifies research and methodological gaps for the use of passive samplers in
monitoring. The main gaps are; i) the range of passive samplers used should be
extended, ii) differences observed in absolute concentrations accumulated by
passive samplers and organisms should be understood, and iii) the link between PW
discharge concentrations and observed acute and sub-lethal ecotoxicological end
points in organisms should be investigated.
PMID- 27514440
TI - Isolation and characterization of lignocellulose nanofibers from different wheat
straw pulps.
AB - Wheat straw was cooked under different pulping processes: Soda (100 degrees C, 7%
NaOH, 150min), Kraft (170 degrees C, 16% alkalinity, 25% sulfidity, 40min) and
Organosolv (210 degrees C, 60% ethanol, 60min). Once the pulps were obtained,
lignocellulose nanofibers (LCNF) were isolated by mechanical process and TEMPO
mediated oxidation followed by a high pressure homogenization. After pulping
process, the different pulps were characterized and its chemical composition was
determined. The pulps characterization indicates that the Soda process is the
process that, despite producing less delignification, retains much of the
hemicelluloses in the pulp, being this content a key factor in the
nanofibrillation process. Regarding the LCNF obtained by mechanical process,
those nanofibers isolated from Organosolv wheat pulp (OWP) and Kraft wheat pulp
(KWP) show low values for nanofibrillation yield, specific surface area and
greater diameter. However, those nanofibers isolated from Soda wheat pulp (SWP)
reach much higher values for these parameters and presents a diameter of 14nm,
smaller than those obtained by TEMPO-mediated oxidation from OWP. Smaller
diameters are generally obtained in TEMPO-oxidized LCNF. This work concludes that
the lignin content does not affect greatly to obtain LCNF as does the
hemicellulose content, so it is accurate to use a soft pulping process.
PMID- 27514441
TI - Interpenetrating hydrogels of O-carboxymethyl Tamarind gum and alginate for
monitoring delivery of acyclovir.
AB - In this work, an interpenetrating hydrogel network was constructed using varying
combination of O-carboxymethyl Tamarind gum (CTG) and alginate by Ca+2 ion
induced gelation method. The hydrogels were characterized by FTIR spectroscopy,
Field emission scanning electron microscopy (FESEM), energy dispersive X-ray
(EDX) and differential scanning calorimetry (DSC) analyses. The hydrogels were
spherical in shape with rough surface textures. Depending on the alginate: CTG
mass ratio, the hydrogel particles entrapped a maximum of ~70% acyclovir. The
drug release from interpenetrating hydrogels was 18-23% in HCl solution (pH1.2)
in 2h. The drug release became faster in phosphate buffer solution (pH6.8) as the
proportion of CTG was increased from 25% to 50%. However, the drug release was
still slower than that observed for hydrogel particles of sodium alginate alone.
Overall, the drug release tendency of the particles was higher in phosphate
buffer solution than that in HCl solution. The non-Fickian drug release behavior
was assumed after fitting the drug release data into Korsmeyer-Peppas model. The
drug release was found to control by diffusion and swelling kinetics of the
hydrogels. Thus, CTG gum could effectively retard drug release when used in
combination with sodium alginate at an optimized mass ratio.
PMID- 27514442
TI - Modified pectin from Theobroma cacao induces potent pro-inflammatory activity in
murine peritoneal macrophage.
AB - In vitro effects of acetylated pectin (OP) isolated from cacao pod husks
(Theobroma cacao L.), its partially deacetylated and de-esterified form (MOP),
and a commercial homogalacturonan (PG) were investigated on murine peritoneal
macrophages. MOP stood out among the studied pectins. After 48h of incubation,
compared with the control group, it was able to promote significant macrophage
morphological differentiation from resident to activated stage and also
stimulated nitric oxide production, which reached a level of 85% of that of LPS
stimulus. In the presence of the highest tested concentration of MOP (200MUg.mL
1), the levels of the cytokines TNF-alpha (6h) and IL-12 and IL-10 (48h)
increased substantially in relation to untreated cells. Our results show that the
partial deacetylation and de-esterification of pectin extracted from cacao pod
husks (T. cacao L.) produced a polymer with greater ability than its native form
to activate macrophages to a cytotoxic phenotype. Like this, they provide the
possibility of a therapeutic application to MOP, which could lead to a decreased
susceptibility to microbial infection besides antitumor activity. Additionally,
the present results also corroborate with the proposition of that the chemical
modifications of the biopolymers can result in an improved molecule with new
possibilities of application.
PMID- 27514443
TI - Dietary litchi pulp polysaccharides could enhance immunomodulatory and
antioxidant effects in mice.
AB - The purpose of this study was to investigate the immunomodulatory and antioxidant
activities of litchi pulp polysaccharides (LP) in cyclophosphamide (Cy)-induced
mice. The administration of LP (50, 100 and 200mg/kg/d) remarkably enhanced
mesenteric lymph node cells proliferation and serum IgA. Moreover, IL-6, TNF
alpha, IgG and IgM levels in serum were significantly improved in a dose
dependent manner with LP treatment. Dietary LP induced systemic immune responses
including stimulating the proliferation of splenocytes, balancing the ratio of
spleen lymphocyte subsets, up-regulating the thymus and spleen indices. Thus, we
speculate litchi polysaccharides would express their systemic immunomodulatory
effects by triggering the intestinal mucosal immunity. Likewise, LP also
significantly increased total antioxidant capacity, as well as superoxidase
dismutase and glutathione peroxidase activity, while decreasing malondialdehyde
levels in the serum and liver. The immunomodulatory activity of LP was
accompanied with its antioxidant activity, which might be related with its
structure and prebiotic effect. This is a novel study on the relationship between
the immunomodulatory and antioxidant activities of litchi polysaccharides.
PMID- 27514444
TI - Structural and thermodynamic studies of the tobacco calmodulin-like rgs-CaM
protein.
AB - The tobacco calmodulin-like protein rgs-CaM is involved in host defense against
virus and is reported to possess an associated RNA silencing suppressor activity.
Rgs-CaM is also believed to act as an antiviral factor by interacting and
targeting viral silencing suppressors for autophagic degradation. Despite these
functional data, calcium interplay in the modulation of rgs-CaM is still poorly
understood. Here we show that rgs-CaM displays a prevalent alpha-helical
conformation and possesses three functional Ca2+-binding sites. Using
computational modeling and molecular dynamics simulation, we demonstrate that
Ca2+ binding to rgs-CaM triggers expansion of its tertiary structure with
reorientation of alpha-helices within the EF-hands. This conformational change
leads to the exposure of a large negatively charged region that may be implicated
in the electrostatic interactions between rgs-CaM and viral suppressors.
Moreover, the kd values obtained for Ca2+ binding to the three functional sites
are not within the affinity range of a typical Ca2+ sensor.
PMID- 27514445
TI - A Prospective, Randomized Study of an Expanded Polytetrafluoroethylene Stent
Graft versus Balloon Angioplasty for In-Stent Restenosis in Arteriovenous Grafts
and Fistulae: Two-Year Results of the RESCUE Study.
AB - PURPOSE: To assess the safety and efficacy of an expanded polytetrafluoroethylene
stent graft versus balloon angioplasty for the treatment of in-stent restenosis
in the venous outflow of hemodialysis access grafts and fistulae. MATERIALS AND
METHODS: Two hundred seventy-five patients were randomized at 23 US sites to
stent-graft placement or percutaneous transluminal angioplasty (PTA). Primary
study endpoints were access circuit primary patency (ACPP) at 6 months and safety
through 30 days; secondary endpoints were evaluated through 24 months. RESULTS:
ACPP at 6 months was significantly higher in the stent-graft group (18.6%) versus
the PTA group (4.5%; P < .001), and freedom from safety events (30 days) was
comparable (stent graft, 96.9%; PTA, 96.4%; P = .003 for noninferiority). The
separation in ACPP survival curves remained through 12 months (stent graft, 6.2%;
PTA, 1.5%). Treatment area primary patency (TAPP) was superior for the stent
graft group (66.4%) versus the PTA group (12.3%) at 6 months (P < .001), with a
survivorship difference in favor of stent-graft placement maintained through 24
months (stent graft, 15.6%; PTA, 2.2%). ACPP and TAPP for the stent-graft group
were better than those for the PTA group when compared within central and
peripheral vein subgroups (P < .001). In central veins, TAPP was 13.6% in the
stent-graft group versus 4.3% in the PTA group at 24 months (P < .001).
CONCLUSIONS: Stent-graft use provided better ACPP and TAPP than PTA when treating
in-stent restenosis in patients receiving dialysis with arteriovenous grafts and
fistulae.
PMID- 27514446
TI - Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of
HD striatal susceptibility.
AB - Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative
disorder that primarily affects medium spiny neurons within the striatum. HD is
caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a
mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the
advances in understanding the molecular mechanisms involved in HD the
preferential vulnerability of the striatum remains an intriguing question. This
review discusses current knowledge that links altered mitochondrial dynamics with
striatal susceptibility in HD. We also highlight how the modulation of
mitochondrial function may constitute an attractive therapeutic approach to
reduce mHtt-induced toxicity and therefore prevent the selective striatal
neurodegeneration.
PMID- 27514447
TI - Secretory expression of a heterologous protein, Aiio-AIO6BS, in Bacillus subtilis
via a non-classical secretion pathway.
AB - The quenching enzyme AIO6 (AiiO-AIO6) has been reported as a feed additive
preparation for application in aquaculture and biological control of pathogenic
Aeromonas hydrophila. We developed an economical strategy to express AIO6BS (AiiO
AIO6BS, codon optimized AIO6 in Bacillus subtilis) in Bacillus subtilis for
facilitating its widespread application. Promoter p43 without the signal peptide
was used for secretory expression of AIO6BS in B. subtilis. Western blotting
analysis demonstrated that AIO6BS was successfully expressed and secreted into
the cell culture. Expression analysis of AIO6BS in the single or double mutant of
the lytC and lytD genes for cell autolysis in B. subtilis 1A751 and cell
autolysis-resistant engineered strain LM2531 derived from the wild type 168
indicated that the release of the heterologous protein AIO6BS was not simply
mediated by cell lysis. Expression level of AIO6BS did not change in the mutants
of B. subtilis that harbored mutations in the secA, tatAC, or ecsA genes compared
with that in the parent wild type strain. These results suggested the AIO6BS
protein was likely secreted via a non-classical secretion pathway. The expression
analysis of the various N- or C-terminal truncated gene products indicated that
AIO6BS probably acts as an export signal to direct its self-secretion across the
cell membrane.
PMID- 27514448
TI - SIRT1 controls cell proliferation by regulating contact inhibition.
AB - Contact inhibition keeps cell proliferation in check and serves as a built-in
protection against cancer development by arresting cell division upon cell-cell
contact. Yet the complete mechanism behind this anti-cancer process remains
largely unclear. Here we present SIRT1 as a novel regulator of contact
inhibition. SIRT1 performs a wide variety of functions in biological processes,
but its involvement in contact inhibition has not been explored to date. We used
NIH3T3 cells, which are sensitive to contact inhibition, and H460 and DU145
cancer cells, which lack contact inhibition, to investigate the relationship
between SIRT1 and contact inhibition. We show that SIRT1 overexpression in NIH3T3
cells overcomes contact inhibition while SIRT1 knockdown in cancer cells restores
their lost contact inhibition. Moreover, we demonstrate that p27 protein
expression is controlled by SIRT1 in contact inhibition. Overall, our findings
underline the critical role of SIRT1 in contact inhibition and suggest SIRT1
inhibition as a potential strategy to suppress cancer cell growth by restoring
contact inhibition.
PMID- 27514449
TI - Diethylnitrosamine-induced expression of germline-specific genes and pluripotency
factors, including vasa and oct4, in medaka somatic cells.
AB - Various methods have been developed to reprogram mammalian somatic cells into
pluripotent cells as well as to directly reprogram somatic cells into other cell
lineages. We are interested in applying these methods to fish, and here, we
examined whether mRNA expression of germline-specific genes (vasa, nanos2, -3)
and pluripotency factors (oct4, sox2, c-myc, nanog) is inducible in somatic cells
of Japanese medaka (Oryzias latipes). We found that the expression of vasa is
induced in the gut and regenerating fin by exposure to a carcinogen,
diethylnitrosamine (DEN). Induction of vasa in the gut started on the 5th day of
treatment with >50 ppm DEN. In addition, nanos2, -3, oct4, sox2, klf4, c-myc, and
nanog were also expressed simultaneously in some vasa-positive gut and
regenerating fin samples. Vasa-positive cells were detected by
immunohistochemistry (IHC) in the muscle surrounding the gut and in the wound
epidermis, blastema, and fibroblast-like cells in regenerating fin. In vasa:GFP
transgenic medaka, green fluorescent protein (GFP) fluorescence appeared in the
wound epidermis and fibroblast-like cells in the regenerating fin following DEN
exposure, in agreement with the IHC data. Our data show that mRNA expression of
genes relevant to germ cell specification and pluripotency can be induced in fish
somatic cells by exposure to DEN, suggesting the possibility of efficient and
rapid cell reprogramming of fish somatic cells.
PMID- 27514450
TI - MicroRNA-2400 promotes bovine preadipocyte proliferation.
AB - MicroRNAs (miRNAs) play critical roles in the proliferation of bovine
preadipocytes. miR-2400 is a novel and unique miRNA from bovines. In the present
study, we separated and identified preadipocytes from bovine samples. miR-2400
overexpression increased the rate of preadipocyte proliferation, which was
analyzed with a combination of EdU and flow cytometry. Simultaneously, functional
genes related to proliferation (PCNA, CCND2, CCNB1) were also increased, which
was detected by real-time PCR. Furthermore, luciferase reporter assays showed
that miR-2400 bound directly to the 3'untranslated regions (3'UTRs) of PRDM11
mRNA. These data suggested that miR-2400 could promote preadipocyte proliferation
by targeting PRDM11.
PMID- 27514451
TI - Analysis and quality control of carbohydrates in therapeutic proteins with
fluorescence HPLC.
AB - Conbercept is an Fc fusion protein with very complicated carbohydrate profiles
which must be carefully monitored through manufacturing process. Here, we
introduce an optimized fluorescence derivatization high-performance liquid
chromatographic method for glycan mapping in conbercept. Compared with
conventional glycan analysis method, this method has much better resolution and
higher reproducibility making it excellent for product quality control.
PMID- 27514452
TI - Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in
neurodegenerative disorders.
AB - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and
they serve to be a promising therapeutic target for several neurodegenerative
disorders, which includes Parkinson disease, Alzheimer's disease, Huntington
disease and Amyotrophic Lateral Sclerosis. PPARs play an important role in the
downregulation of mitochondrial dysfunction, proteasomal dysfunction, oxidative
stress, and neuroinflammation, which are the major causes of the pathogenesis of
neurodegenerative disorders. In this review, we discuss about the role of PPARs
as therapeutic targets in neurodegenerative disorders. Several experimental
approaches suggest potential application of PPAR agonist as well as antagonist in
the treatment of neurodegenerative disorders. Several epidemiological studies
found that the regular usage of PPAR activating non-steroidal anti-inflammatory
drugs is effective in decreasing the progression of neurodegenerative diseases
including PD and AD. We also reviewed the neuroprotective effects of PPAR
agonists and associated mechanism of action in several neurodegenerative
disorders both in vitro as well as in vivo animal models.
PMID- 27514453
TI - SMARTER De-Stressed Cereal Breeding.
AB - In cereal breeding programs, improved yield potential and stability are ultimate
goals when developing new varieties. To facilitate achieving these goals,
reproductive success under stressful growing conditions is of the highest
priority. In recent times, small RNA (sRNA)-mediated pathways have been
associated with the regulation of genes involved in stress adaptation and
reproduction in both model plants and several cereals. Reproductive and
physiological traits such as flowering time, reproductive branching, and root
architecture can be manipulated by sRNA regulatory modules. We review sRNA
mediated pathways that could be exploited to expand crop diversity with adaptive
traits and, in particular, the development of high-yielding stress-tolerant
cereals: SMARTER cereal breeding through 'Small RNA-Mediated Adaptation of
Reproductive Targets in Epigenetic Regulation'.
PMID- 27514454
TI - Take a Trip Through the Plant and Fungal Transportome of Mycorrhiza.
AB - Soil nutrient acquisition and exchanges through symbiotic plant-fungus
interactions in the rhizosphere are key features for the current agricultural and
environmental challenges. Improved crop yield and plant mineral nutrition through
a fungal symbiont has been widely described. In return, the host plant supplies
carbon substrates to its fungal partner. We review here recent progress on
molecular players of membrane transport involved in nutritional exchanges between
mycorrhizal plants and fungi. We cover the transportome, from the transport
proteins involved in sugar fluxes from plants towards fungi, to the uptake from
the soil and exchange of nitrogen, phosphate, potassium, sulfate, and water.
Together, these advances in the comprehension of the mycorrhizal transportome
will help in developing the future engineering of new agro-ecological systems.
PMID- 27514455
TI - Macrophages induce resistance to 5-fluorouracil chemotherapy in colorectal cancer
through the release of putrescine.
AB - The development of chemoresistance to 5-fluorouracil (5-FU) is a major obstacle
for sustained effective treatment of colorectal cancer (CRC), with the mechanisms
being not fully understood. Here we demonstrated that tumor associated
macrophages (TAMs) became activated during treatment with 5-FU and secreted
factors that protected the CRC cells against chemotherapy with 5-FU. By
performing metabolomics analysis, we identified putrescine, a member of
polyamines, inducing resistance to 5-FU-triggered CRC apoptosis and tumor
suppression via JNK-caspase-3 pathway. Noteworthily, either pharmacological or
genetic blockage of ornithine decarboxylase (ODC) prevented TAMs-induced
chemoresistance to 5-FU in vitro and in vivo. Our findings show that TAMs are
potent mediators of resistance to 5-FU chemotherapy and uncover potential targets
to enhance chemotherapy sensitivity in patients with CRC.
PMID- 27514456
TI - A new and simple suturing technique applied after surgery to correct ingrown
toenails may improve clinical outcomes: A randomized controlled trial.
AB - INTRODUCTION: In the present study, we investigated the efficacy of a new
suturing technique applied after the Winograd procedure has been completed.
METHODS: This study was prospective, randomized, and controlled. In total, 128
patients were recruited and divided into two groups. The outcomes of those
treated with the new suturing technique (group I) were compared with those of
patients treated with the traditional suturing technique (group II), both of
which were applied after the Winograd procedure had been completed. The clinical
outcomes and recurrence rates of the two groups were compared. RESULTS: Patients
in group I required significantly more time to return to work or school than did
those in group II (p = 0.015). We found no significant difference between youths
(age < 18 years, n = 55) and adults (age >= 19 years, n = 69) in this context (p
= 0.161). The recurrence rate was significantly higher in group II than in group
I (p = 0.011). The extent of satisfaction was significantly higher in group I (p
= 0.042). CONCLUSIONS: Our new suturing technique is associated with lower
recurrence and higher satisfaction rates. However, the times elapsing before
shoes could be worn were similar in the two groups.
PMID- 27514457
TI - Cerebral Air Embolism During Air Flight-Neuroimaging and Management.
PMID- 27514458
TI - Leg Lift Valsalva Maneuver for Treatment of Supraventricular Tachycardias.
AB - Clinical question Can conversion to sinus rhythm for a supraventricular
tachycardia be enhanced by a postural modification to the Valsalva maneuver?
Article chosen Appelboam A, Reuben A, Mann C, et al. Postural modification of the
standard Valsalva manoeuvre for emergency treatment of supraventricular
tachycardias (REVERT): a randomised controlled trial. Lancet 2015;386(10005):1747
53. 1 OBJECTIVE: To determine effectiveness of a postural modification of the
Valsalva involving leg elevation and supine positioning.
PMID- 27514459
TI - Synthesis of cyclic carbonates from diols and CO2 catalyzed by carbenes.
AB - The synthesis of cyclic carbonates from epoxides and CO2 is a well-established
reaction, whereas the synthesis of cyclic carbonates from diols and CO2 is
considerably more challenging, and few efficient catalysts are available. Here,
we describe heterocyclic carbene catalysts, including one derived from a cheap
and efficient thiazolium salt, for this latter reaction. The reaction proceeds at
atmospheric pressure in the presence of an alkyl halide and Cs2CO3. Reaction
mechanisms for the transformations involved are also proposed.
PMID- 27514460
TI - Elevated cardiac 3-deoxyglucosone, a highly reactive intermediate in glycation
reaction, in doxorubicin-induced cardiotoxicity in rats.
AB - 3-Deoxyglucosone (3-DG) is a highly reactive carbonyl intermediate in glycation
reaction (also known as Maillard reaction) and plays an important role in
diabetic complications. We investigated the potential involvement of 3-DG in
doxorubicin (DXR)-induced cardiotoxicity. Male Crl:CD(SD) rats received
intravenous injections of DXR at 2mg/kg, once weekly, for 6 weeks, with/without
daily intraperitoneal treatment with 3-DG scavenging agents, i.e., aminoguanidine
(AG, 25mg/kg/day) and pyridoxamine (PM, 60mg/kg/day). Cardiac levels of 3-DG,
thiobarbituric acid reactive substances (TBARS), fructosamine, and pentosidine,
plasma glucose levels and cardiac troponin I (cTnI), echocardiography, and
histopathology were assessed at 4 and 6 weeks after treatment. Cardiac 3-DG
levels were significantly increased by DXR treatment at 4 and 6 weeks. Cardiac
fructosamine levels and plasma glucose were not altered by DXR; however, TBARS
levels in the heart were significantly increased at 4 and 6 weeks, suggesting
that the enhanced generation of 3-DG is not attributed to any abnormal glycemic
status, but may be related to oxidative stress by DXR. An advanced glycation end
product, pentosidine, was significantly increased by DXR treatment at 6 weeks.
Intervention by AG and PM ameliorated the DXR-induced echocardiographic
abnormalities, increased cTnI in plasma, and histopathological lesion as well as
normalizing the elevation of 3-DG and pentosidine levels. These results suggest
that 3-DG is generated by DXR and involved, at least in part, in the pathogenesis
of DXR-cardiotoxicity through glycation reaction.
PMID- 27514461
TI - Fundamentals of Pharmacogenetics in Personalized, Precision Medicine.
AB - This article introduces fundamental principles of pharmacogenetics as applied to
personalized and precision medicine. Pharmacogenetics establishes relationships
between pharmacology and genetics by connecting phenotypes and genotypes in
predicting the response of therapeutics in individual patients. We describe
differences between precision and personalized medicine and relate principles of
pharmacokinetics and pharmacodynamics to applications in laboratory medicine. We
also review basic principles of pharmacogenetics, including its evolution, how it
enables the practice of personalized therapeutics, and the role of the clinical
laboratory. These fundamentals are a segue for understanding specific clinical
applications of pharmacogenetics described in subsequent articles in this issue.
PMID- 27514462
TI - Pharmacogenetics in Oral Antithrombotic Therapy.
AB - Certain antithrombotic drugs exhibit high patient-to-patient variability that
significantly impacts the safety and efficacy of therapy. Pharmacogenetics offers
the possibility of tailoring drug treatment to patients based on individual
genotypes, and this type of testing has been recommended for 2 oral
antithrombotic agents, warfarin and clopidogrel, to influence use and guide
dosing. Limited studies have identified polymorphisms that affect the metabolism
and activity of newer oral antithrombotic drugs, without clear evidence of the
clinical relevance of such polymorphisms. This article provides an overview of
the current status of pharmacogenetics in oral antithrombotic therapy.
PMID- 27514464
TI - Pharmacogenetics and Personalized Medicine in Pain Management.
AB - Genetic research heralds a new therapeutic approach to pain management.
Increasing literature demonstrates individual genetic vulnerabilities to specific
pain types and mechanisms, partially explaining differing responses to similar
pain stimuli. Furthermore, analgesics demonstrate great variability among
carriers of different genotypes. Family history and genotyping promise to play an
important role in the future approach to pain therapies. As advances continue in
the genetics of pain and analgesia, pharmacotherapy will depend more on an
individualized, targeted approach and less on empiricism.
PMID- 27514463
TI - Laboratory Medicine in the Clinical Decision Support for Treatment of
Hypercholesterolemia: Pharmacogenetics of Statins.
AB - Statin responsiveness is an area of great research interest given the success of
the drug class in the treatment of hypercholesterolemia and in primary and
secondary prevention of cardiovascular disease. Interrogation of the patient's
genome for gene variants will eventually guide anti-hyperlipidemic intervention.
In this review, we discuss methodological approaches to discover genetic markers
predictive of class-wide and drug-specific statin efficacy and safety. Notable
pharmacogenetic findings are summarized from hypothesis-free genome wide and
hypothesis-led candidate gene association studies. Physiogenomic models and
clinical decision support systems will be required for DNA-guided statin therapy
to reach practical use in medicine.
PMID- 27514465
TI - Pharmacogenomics in Psychiatric Practice.
AB - Pharmacogenomic testing in psychiatry is becoming an established clinical
procedure. Several vendors provide clinical interpretation of combinatorial
pharmacogenomic testing of gene variants that have documented predictive
implications regarding either pharmacologic response or adverse effects in
depression and other psychiatric conditions. Such gene profiles have demonstrated
improvements in outcome in depression, and reduction of cost of care of patients
with inadequate clinical response. Additionally, several new gene variants are
being studied to predict specific response in individuals. Many of these genes
have demonstrated a role in the pathophysiology of depression or specific
depressive symptoms. This article reviews the current state-of-the-art
application of psychiatric pharmacogenomics.
PMID- 27514466
TI - Clinical Utility and Economic Impact of CYP2D6 Genotyping.
AB - Pharmacogenetics examines an individual's genetic makeup to help predict the
safety and efficacy of medications. Practical application optimizes treatment
selection to decrease the failure rate of medications and improve clinical
outcomes. Lack of efficacy is costly due to adverse drug reactions and increased
hospital stays. Cytochrome P450 2D6 (CYP2D6) metabolizes roughly 25% of all
drugs. Detecting variants that cause altered CYP2D6 enzymatic activity identifies
patients at risk of adverse drug reactions or therapeutic failure with standard
dosages of medications metabolized by CYP2D6. This article discusses the clinical
application of pharmacogenetics to improve care and decrease costs.
PMID- 27514467
TI - The Pharmacist's Perspective on Pharmacogenetics Implementation.
AB - The future for pharmacogenetics will continue to expand. Pharmacists can apply
and incorporate drug knowledge in collaboration with other health providers using
pharmacogenetics. Patients benefit with enhanced therapeutic outcomes that could
lead to more streamlined drug approaches, fewer follow-up visits, cost savings,
and shorter times to achieve therapeutic outcomes. As more drug-gene pathways are
discovered and use of this knowledge increases, the potential for algorithm
development for medication use will occur, resulting in better patient outcomes,
higher standard of care, and reflect evidence-based medicine.
PMID- 27514468
TI - The Future of Precision Medicine in Oncology.
AB - Precision medicine in oncology focuses on identifying which therapies are most
effective for each patient based on genetic characterization of the cancer.
Traditional chemotherapy is cytotoxic and destroys all cells that are rapidly
dividing. The foundation of precision medicine is targeted therapies and
selecting patients who will benefit most from these therapies. One of the newest
aspects of precision medicine is liquid biopsy. A liquid biopsy includes analysis
of circulating tumor cells, cell-free nucleic acid, or exosomes obtained from a
peripheral blood draw. These can be studied individually or in combination and
collected serially, providing real-time information as a patient's cancer
changes.
PMID- 27514469
TI - Understanding the Food and Drug Administration's Jurisdiction Over Laboratory
Developed Tests and Divisions Between Food, Drug, and Cosmetic Act-Regulated and
Clinical Laboratory Improvement Amendments of 1988-Regulated Activities.
AB - The scope of FDA's jurisdiction over laboratory-developed tests (LDTs), and
whether FDA has such jurisdiction at all, has been a heavily debated issue over
the past several years. If FDA moves forward with its guidance, or Congress takes
action to reform LDT and IVD regulation, a fundamental question that needs to be
answered is how to divide activities regulated by FDCA from those regulated by
CLIA. In this article, we consider FDA's authority to regulate LDTs and the
policy implications of regulation, and discuss an idea for a fact-driven
framework to distinguish FDCA- and CLIA- activities.
PMID- 27514470
TI - Extracellular Vesicles Move Toward Use in Clinical Laboratories.
AB - Extracellular vesicles (EVs) are membranous particles found in a variety of
biofluids that encapsulate molecular information from the cell, which they
originate from. This rich source of information that is easily obtained can then
be mined to find diagnostic biomarkers. This article explores the current
biological understanding of EVs and specific methods to isolate and analyze them.
A case study of a company leading the charge in using EVs in diagnostic assays is
provided.
PMID- 27514471
TI - Preface.
PMID- 27514472
TI - DELLA proteins are common components of symbiotic rhizobial and mycorrhizal
signalling pathways.
AB - Legumes form symbiotic associations with either nitrogen-fixing bacteria or
arbuscular mycorrhizal fungi. Formation of these two symbioses is regulated by a
common set of signalling components that act downstream of recognition of
rhizobia or mycorrhizae by host plants. Central to these pathways is the calcium
and calmodulin-dependent protein kinase (CCaMK)-IPD3 complex which initiates
nodule organogenesis following calcium oscillations in the host nucleus. However,
downstream signalling events are not fully understood. Here we show that Medicago
truncatula DELLA proteins, which are the central regulators of gibberellic acid
signalling, positively regulate rhizobial symbiosis. Rhizobia colonization is
impaired in della mutants and we provide evidence that DELLAs can promote CCaMK
IPD3 complex formation and increase the phosphorylation state of IPD3. DELLAs can
also interact with NSP2-NSP1 and enhance the expression of Nod-factor-inducible
genes in protoplasts. We show that DELLA is able to bridge a protein complex
containing IPD3 and NSP2. Our results suggest a transcriptional framework for
regulation of root nodule symbiosis.
PMID- 27514473
TI - ERAP1-ERAP2 dimers trim MHC I-bound precursor peptides; implications for
understanding peptide editing.
AB - The processing of MHC class I antigenic precursor peptides by the endoplasmic
reticulum aminopeptidase 1 (ERAP1) and ERAP2 is an important event in the cell
biology of antigen presentation. To date, the molecular context by which the ERAP
enzymes trim precursor peptides, and how ERAPs shape peptide repertoires, remain
open questions. Using ERAP1 and ERAP2 heterodimers (ERAP1/2), and N-terminally
extended model and natural peptides in their free and HLA-B*0801-bound forms, we
characterized the mode of action of ERAPs. We provide evidence that ERAP1/2 can
trim MHC I-bound precursor peptides to their correct and final lengths, albeit
more slowly than the corresponding free precursors. Trimming of MHC I-bound
precursors by ERAP1/2 increases the conformational stability of MHC I/peptide
complexes. From the data, we propose a molecular mechanistic model of ERAP1/2 as
peptide editors. Overall, our study provides new findings on a significant issue
of the ERAP-mediated processing pathway of MHC class I antigens.
PMID- 27514474
TI - Influence of grain boundary characteristics on thermal stability in nanotwinned
copper.
AB - High density grain boundaries provide high strength, but may introduce
undesirable features, such as high Fermi levels and instability. We investigated
the kinetics of recovery and recrystallization of Cu that was manufactured to
include both nanotwins (NT) and high-angle columnar boundaries. We used the
isothermal Johnson-Mehl-Avrami-Kolmogorov (JMAK) model to estimate activation
energy values for recovery and recrystallization and compared those to values
derived using the non-isothermal Kissinger equation. The JMAK model hinges on an
exponent that expresses the growth mechanism of a material. The exponent for this
Cu was close to 0.5, indicating low-dimensional microstructure evolution, which
is associated with anisotropic twin coarsening, heterogeneous recrystallization,
and high stability. Since this Cu was of high purity, there was a negligible
impurity-drag-effect on boundaries. The twin coarsening and heterogeneous
recrystallization resulted from migration of high-angle columnar boundaries with
their triple junctions in one direction, assisted by the presence of high
concentration vacancies at boundaries. Analyses performed by electron energy loss
spectroscopy of atomic columns at twin boundaries (TBs) and in the interior
showed similar plasma peak shapes and L3 edge positions. This implies that values
for conductivity and Fermi level are equal for atoms at TBs and in the interior.
PMID- 27514475
TI - Legumain is activated in macrophages during pancreatitis.
AB - Pancreatitis is an inflammatory disease of the pancreas characterized by
dysregulated activity of digestive enzymes, necrosis, immune infiltration, and
pain. Repeated incidence of pancreatitis is an important risk factor for
pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to
inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now,
legumain activation has not been studied during pancreatitis. We used a
fluorescently quenched activity-based probe to assess legumain activation during
caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo
imaging, confocal microscopy, and gel electrophoresis. Compared with healthy
controls, legumain activity in the pancreas of caerulein-treated mice was
increased in a time-dependent manner. Legumain was localized to CD68(+)
macrophages and was not active in pancreatic acinar cells. Using a small-molecule
inhibitor of legumain, we found that this protease is not essential for the
initiation of pancreatitis. However, it may serve as a biomarker of disease,
since patients with chronic pancreatitis show strongly increased legumain
expression in macrophages. Moreover, the occurrence of legumain-expressing
macrophages in regions of acinar-to-ductal metaplasia suggests that this protease
may influence reprogramming events that lead to inflammation-induced pancreatic
cancer.
PMID- 27514477
TI - Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide
expression and microbial diversity.
AB - The cholinergic anti-inflammatory pathway reduces systemic tumor necrosis factor
(TNF) via acetylcholine-producing memory T cells in the spleen. These choline
acetyltransferase (ChAT)-expressing T cells are also found in the intestine,
where their function is unclear. We aimed to characterize these cells in mouse
and human intestine and delineate their function. We made use of the ChAT
enhanced green fluorescent protein (eGFP) reporter mice. CD4Cre mice were crossed
to ChATfl/fl mice to achieve specific deletion of ChAT in CD4+ T cells. We
observed that the majority of ChAT-expressing T cells in the human and mouse
intestine have characteristics of Th17 cells and coexpress IL17A, IL22, and RORC
The generation of ChAT-expressing T cells was skewed by dendritic cells after
activation of their adrenergic receptor beta2 To evaluate ChAT T cell function,
we generated CD4-specific ChAT-deficient mice. CD4ChAT-/- mice showed a reduced
level of epithelial antimicrobial peptides lysozyme, defensin A, and ang4, which
was associated with an enhanced bacterial diversity and richness in the small
intestinal lumen in CD4ChAT-/- mice. We conclude that ChAT-expressing T cells in
the gut are stimulated by adrenergic receptor activation on dendritic cells. ChAT
expressing T cells may function to mediate the host AMP secretion, microbial
growth and expansion.
PMID- 27514476
TI - Soluble bioactive microbial mediators regulate proteasomal degradation and
autophagy to protect against inflammation-induced stress.
AB - Bifidobacterium breve and other Gram-positive gut commensal microbes protect the
gastrointestinal epithelium against inflammation-induced stress. However, the
mechanisms whereby these bacteria accomplish this protection are poorly
understood. In this study, we examined soluble factors derived from
Bifidobacterium breve and their impact on the two major protein degradation
systems within intestinal epithelial cells, proteasomes and autophagy.
Conditioned media from gastrointestinal Gram-positive, but not Gram-negative,
bacteria activated autophagy and increased expression of the autophagy proteins
Atg5 and Atg7 along with the stress response protein heat shock protein 27.
Specific examination of media conditioned by the Gram-positive bacterium
Bifidobacterium breve (Bb-CM) showed that this microbe produces small molecules
(<3 kDa) that increase expression of the autophagy proteins Atg5 and Atg7,
activate autophagy, and inhibit proteasomal enzyme activity. Upregulation of
autophagy by Bb-CM was mediated through MAP kinase signaling. In vitro studies
using C2BBe1 cells silenced for Atg7 and in vivo studies using mice conditionally
deficient in intestinal epithelial cell Atg7 showed that Bb-CM-induced
cytoprotection is dependent on autophagy. Therefore, this work demonstrates that
Gram-positive bacteria modify protein degradation programs within intestinal
epithelial cells to promote their survival during stress. It also reveals the
therapeutic potential of soluble molecules produced by these microbes for
prevention and treatment of gastrointestinal disease.
PMID- 27514478
TI - Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated
Clostridium difficile-associated cecal inflammation in hamsters.
AB - C. difficile infection (CDI) is a common debilitating nosocomial infection
associated with high mortality. Several CDI outbreaks have been attributed to
ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that
the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for
the prevention of CDI. However, there is no current evidence suggesting this
probiotic can protect from CDI caused by outbreak-associated strains. We used
established hamster models infected with outbreak-associated C. difficile strains
to determine whether oral administration of live or heat-inactivated S.b can
prevent cecal tissue damage and inflammation. Hamsters infected with C. difficile
strain VPI10463 (ribotype 087) and outbreak-associated strains ribotype 017, 027,
and 078 developed severe cecal inflammation with mucosal damage, neutrophil
infiltration, edema, increased NF-kappaB phosphorylation, and increased
proinflammatory cytokine TNFalpha protein expression. Oral gavage of live, but
not heated, S.b starting 5 days before C. difficile infection significantly
reduced cecal tissue damage, NF-kappaB phosphorylation, and TNFalpha protein
expression caused by infection with all strains. Moreover, S.b-conditioned medium
reduced cell rounding caused by filtered supernatants from all C. difficile
strains. S.b-conditioned medium also inhibited toxin A- and B-mediated actin
cytoskeleton disruption. S.b is effective in preventing C. difficile infection by
outbreak-associated via inhibition of the cytotoxic effects of C. difficile
toxins.
PMID- 27514479
TI - The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease
in mice.
AB - Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver
disease and is increasing with the rising rate of obesity in the developed world.
Signaling pathways known to influence the rate of lipid deposition in liver,
known as hepatic steatosis, include the transforming growth factor (TGF)
superfamily, which function through the SMAD second messengers. The
kielin/chordin-like protein (KCP) is a large secreted protein that can enhance
bone morphogenetic protein signaling while suppressing TGF-beta signaling in
cells and in genetically modified mice. In this report, we show that aging KCP
mutant (Kcp-/-) mice are increasingly susceptible to developing hepatic steatosis
and liver fibrosis. When young mice are put on a high-fat diet, Kcp-/- mice are
also more susceptible to developing liver pathology, compared with their wild
type littermates. Furthermore, mice that express a Pepck-KCP transgene (KcpTg) in
the liver are resistant to developing liver pathology even when fed a high-fat
diet. Analyses of liver tissues reveal a significant reduction of P-Smad3,
consistent with a role for KCP in suppressing TGF-beta signaling. Transcriptome
analyses show that livers from Kcp-/- mice fed a normal diet are more like wild
type livers from mice fed a high-fat diet. However, the KCP transgene can
suppress many of the changes in liver gene expression that are due to a high-fat
diet. These data demonstrate that shifting the TGF-beta signaling paradigm with
the secreted regulatory protein KCP can significantly alter the liver pathology
in aging mice and in diet-induced NAFLD.
PMID- 27514480
TI - Ion channelopathies in functional GI disorders.
AB - In the gastrointestinal (GI) tract, abnormalities in secretion, absorption,
motility, and sensation have been implicated in functional gastrointestinal
disorders (FGIDs). Ion channels play important roles in all these GI functions.
Disruptions of ion channels' ability to conduct ions can lead to diseases called
ion channelopathies. Channelopathies can result from changes in ion channel
biophysical function or expression due to mutations, posttranslational
modification, and accessory protein malfunction. Channelopathies are strongly
established in the fields of cardiology and neurology, but ion channelopathies
are only beginning to be recognized in gastroenterology. In this review, we
describe the state of the emerging field of GI ion channelopathies. Several
recent discoveries show that channelopathies result in alterations in GI
motility, secretion, and sensation. In the epithelium, mutations in the cystic
fibrosis transmembrane conductance regulator (CFTR) or CFTR-associating proteins
result in channelopathies with constipation or diarrhea as phenotypes. In the
muscle, mutations in the SCN5A-encoded voltage-gated sodium channel NaV1.5 are
associated with irritable bowel syndrome. In the sensory nerves, channelopathies
of voltage-gated sodium channels NaV1.7 and NaV1.9 (encoded by SCN9A, SCN11A,
respectively) manifest by either GI hyper- or hyposensation. Recent advances in
structural biology and ion channel biophysics, coupled with personalized
medicine, have fueled rapid discoveries of novel channelopathies and direct drug
targeting of specific channelopathies. In summary, the emerging field of GI ion
channelopathies has significant implications for functional GI disease
stratification, diagnosis, and treatment.
PMID- 27514481
TI - Monosodium glutamate inhibits the lymphatic transport of lipids in the rat.
AB - It is not well understood how monosodium glutamate (MSG) affects gastrointestinal
physiology, especially regarding the absorption and the subsequent transport of
dietary lipids into lymph. Thus far, there is little information about how the
ingestion of MSG affects the lipid lipolysis, uptake, intracellular
esterification, and formation and secretion of chylomicrons. Using lymph fistula
rats treated with the infusion of a 2% MSG solution before a continuous infusion
of triglyceride, we show that MSG causes a significant decrease in both
triglyceride and cholesterol secretion into lymph. Intriguingly, the diminished
lymphatic transport of triglyceride and cholesterol was not caused by an
accumulation of these labeled lipids in the intestinal lumen or in the intestinal
mucosa. Rather, it is a result of increased portal transport in the animals fed
acutely the lipid plus 2% MSG in the lipid emulsion. This is a first
demonstration of MSG on intestinal lymphatic transport of lipids.
PMID- 27514482
TI - Measurement of strains experienced by viscerofugal nerve cell bodies during
mechanosensitive firing using digital image correlation.
AB - Mechanosensory neurons detect physical events in the local environments of the
tissues that they innervate. Studies of mechanosensitivity of neurons or nerve
endings in the gut have related their firing to strain, wall tension, or
pressure. Digital image correlation (DIC) is a technique from materials
engineering that can be adapted to measure the local physical environments of
afferent neurons at high resolution. Flat-sheet preparations of guinea pig distal
colon were set up with arrays of tissue markers in vitro. Firing of single
viscerofugal neurons was identified in extracellular colonic nerve recordings.
The locations of viscerofugal nerve cell bodies were inferred by mapping firing
responses to focal application of the nicotinic receptor agonist 1,1-dimethyl-4
phenylpiperazinium iodide. Mechanosensory firing was recorded during load-evoked
uniaxial or biaxial distensions. Distension caused movement of surface markers
which was captured by video imaging. DIC tracked the markers, interpolating the
mechanical state of the gut at the location of the viscerofugal nerve cell body.
This technique revealed heterogeneous load-evoked strain within preparations.
Local strains at viscerofugal nerve cell bodies were usually smaller than global
strain measurements and correlated more closely with mechanosensitive firing.
Both circumferential and longitudinal strain activated viscerofugal neurons.
Simultaneous loading in circumferential and longitudinal axes caused the highest
levels of viscerofugal neuron firing. Multiaxial strains, reflecting tissue
shearing and changing area, linearly correlated with mechanosensory firing of
viscerofugal neurons. Viscerofugal neurons were mechanically sensitive to both
local circumferential and local longitudinal gut strain, and appear to lack
directionality in their stretch sensitivity.
PMID- 27514484
TI - Lysyl oxidase activity in human skin is increased by chronic ultraviolet
radiation exposure and smoking.
PMID- 27514483
TI - Hepatocellular autophagy modulates the unfolded protein response and fasting
induced steatosis in mice.
AB - Autophagy and the unfolded protein response (UPR) are key cellular homeostatic
mechanisms and are both involved in liver diseases, including nonalcoholic fatty
liver disease (NAFLD). Although increasing but conflicting results link these
mechanisms to lipid metabolism, their role and potential cross talk herein have
been poorly investigated. Therefore, we assessed the effects of hepatocyte
specific autophagy deficiency on liver parenchyma, the UPR, and lipid metabolism.
Adult hepatocellular-specific autophagy-deficient mice (Atg7F/FAlb-Cre+) were
compared with their autophagy-competent littermates (Atg7+/+Alb-Cre+). Livers
were analyzed by electron microscopy, histology, real-time qPCR, and Western
blotting. Atg7F/FAlb-Cre+ mice developed hepatomegaly with significant
parenchymal injury, as shown by inflammatory infiltrates, hepatocellular
apoptosis, pericellular fibrosis, and a pronounced ductular reaction.
Surprisingly, the UPR exhibited a pathway-selective pattern upon autophagy
deficiency. The activity of the adaptive activating transcription factor 6 (ATF6)
pathway was abolished, whereas the proapoptotic protein kinase RNA-like ER kinase
pathway was increased compared with Atg7+/+Alb-Cre+ mice. The inositol-requiring
enzyme-1alpha signal was unaltered. Fasting-induced steatosis was absent in
Atg7F/FAlb-Cre+ mice. Remarkably, some isolated islands of fat-containing and
autophagy-competent cells were observed in these livers. Hepatocellular autophagy
is essential for parenchymal integrity in mice. Moreover, in the case of
autophagy deficiency, the three different UPR branches are pathway selectively
modulated. Attenuation of the ATF6 pathway might explain the observed impairment
of fasting-induced steatosis. Finally, autophagy and lipid droplets are directly
linked to each other.
PMID- 27514485
TI - Microwave-Assisted Extraction, Chemical Structures, and Chain Conformation of
Polysaccharides from a Novel Cordyceps Sinensis Fungus UM01.
AB - Cordyceps sinensis is a well-known tonic food with broad medicinal properties.
The aim of the present study was to investigate the optimization of microwave
assisted extraction (MAE) and characterize chemical structures and chain
conformation of polysaccharides from a novel C. sinensis fungus UM01. Ion
exchange and gel filtration chromatography were used to purify the
polysaccharides. The chemical structure of purified polysaccharide was determined
through gas chromatography-mass spectrometry. Moreover, high performance size
exclusion chromatography combined with refractive index detector and multiangle
laser light scattering were conducted to analyze the molecular weight (Mw ) and
chain conformation of purified polysaccharide. Based on the orthogonal design L9
, optimal MAE conditions could be obtained through 1300 W of microwave power,
with a 5-min irradiation time at a solid to water ratio of 1:60, generating the
highest extraction yield of 6.20%. Subsequently, the polysaccharide UM01-S1 was
purified. The UM01-S1 is a glucan-type polysaccharide with a (1->4)-beta-d
glucosyl backbone and branching points located at O-3 of Glcp with a terminal-d
Glcp. The Mw , radius of gyration (Rg ) and hydrodynamic radius (Rh ) of UM01-S1
were determined as 5.442 * 10(6) Da, 21.8 and 20.2 nm, respectively. Using the
polymer solution theory, the exponent (nu) value of the power law function was
calculated as 0.38, and the shape factor (rho = Rg /Rh ) was 1.079, indicating
that UM01-S1 has a sphere-like conformation with a branched structure in an
aqueous solution. These results provide fundamental information for the future
application of polysaccharides from cultured C. sinensis in health and functional
food area.
PMID- 27514486
TI - Estimating risk of malignancy in adnexal masses: external validation of the ADNEX
model and comparison with other frequently used ultrasound methods.
AB - OBJECTIVES: To validate externally the performance of the Assessment of Different
NEoplasias in the adneXa (ADNEX) model and compare this model with other
frequently used models in the differentiation between benign and malignant
adnexal masses. METHODS: In this retrospective diagnostic accuracy study, we
assessed data collected prospectively from patients with adnexal pathology who
underwent real-time transvaginal or transrectal ultrasound by a single expert
ultrasonographer in a tertiary care hospital between July 2011 and July 2015. The
presence of a malignancy was determined by subjective assessment and use of four
prediction models: the ADNEX model, simple ultrasound-based rules (simple rules),
Logistic Regression model 2 (LR2) and the Risk of Malignancy Index (RMI), of
which three different variants were assessed. Pathology was the clinical
reference standard. RESULTS: In total, 851 consecutive patients underwent
ultrasound examination for an adnexal mass. For 326 patients (128 premenopausal
and 198 postmenopausal), pathology results were available (211 (64.7%) benign;
115 (35.3%) malignant) and these were included in the analysis. The area under
the receiver-operating characteristics curve (AUC) of the ADNEX model for the
discrimination between benign and malignant tumors was 0.93 (95% CI, 0.89-0.95).
AUCs for the subtypes of malignancy (i.e. borderline, Stage I-IV and metastatic
adnexal tumors) ranged between 0.60 and 0.90. Only subjective assessment (AUC,
0.96 (95% CI, 0.93-0.98)) was superior to the ADNEX model (P = 0.01) in
differentiating malignant from benign tumors. AUCs for the other models were 0.92
(95% CI, 0.89-0.95) for LR2, 0.85 (95% CI, 0.81-0.89) for RMI-I, 0.82 (95% CI,
0.77-0.86) for RMI-II and 0.84 (95% CI, 0.80-0.88) for RMI-III. At the proposed
cut-off of >= 10%, the ADNEX model had the highest sensitivity (0.98 (95% CI,
0.93-1.00)) but the lowest specificity (0.62 (95% CI, 0.55-0.68)) compared with
the other models. Both subjective assessment (sensitivity, 0.90 (95% CI, 0.83
0.95); specificity 0.91 (95% CI, 0.86-0.94)) and the simple rules model with
inconclusive cases classified by subjective assessment (sensitivity, 0.89 (95%
CI, 0.81-0.94); specificity, 0.90 (95% CI, 0.85-0.94)) had lower sensitivity, but
their sensitivity and specificity were better balanced. CONCLUSIONS: Although the
test performance of subjective assessment by an expert remains superior, the
ADNEX model can help in the differentiation between benign and malignant ovarian
tumors. The advantage of the ADNEX model as a polytomous model remains to be
shown. (c) 2016 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- 27514487
TI - Protective Effect of Curcumin Against Acute Ultraviolet B Irradiation-induced
Photo-damage.
AB - Ultraviolet B (UVB) irradiation is one of the most dangerous insults for skin and
causes sunburn, erythema, photoaging and photocarcinogenesis. Curcumin
(diferuloylmethane), a yellow spice derived from dried rhizomes of Curcuma longa,
has been shown to possess significant anti-inflammatory, antioxidant,
anticarcinogenic, antimutagenic, anticoagulant and anti-infective effects.
However, the protective effects of curcumin against acute photo-damage are poorly
understood. In this study, we investigated the photoprotective effects of
curcumin against UVB-induced acute photo-damage in hairless mice and immortalized
human keratinocytes (HaCaT). Topical application of curcumin significantly
inhibited acute UVB (540 mJ cm-2 , for 3 successive days)-induced inflammatory
cells, collagen accrementition derangement and lipid peroxidation, and
effectively induced NF-E2-related factor 2 (Nrf2) nuclear accumulation in
uncovered (Uncv) hairless mice skin. Treatment of HaCaT cells with curcumin
significantly attenuated acute UVB (300 mJ cm-2 )-induced lactate dehydrogenase
release, intracellular reactive oxygen species production and DNA damage,
activated the expression of the phase II detoxifying enzymes and promoted DNA
repair activity. The photoprotective effect provided by curcumin was potential
associated with modulation of Nrf2-dependent antioxidant response. Our study
suggested that curcumin is a potential agent for preventing and/or treating UV
radiation-induced acute inflammation and photoaging.
PMID- 27514488
TI - Classic Spotlight: Hfq, from a Specific Host Factor for Phage Replication to a
Global Player in Riboregulation.
PMID- 27514489
TI - Classic Spotlight: Look, Max-No Math Required!
PMID- 27514492
TI - Abeta Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be
Prevented by Glutaminase Inhibition Promoting Neuronal Survival.
AB - The E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated
by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic
neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved
in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid
beta (Abeta), a peptide related to Alzheimer's disease, cause proteasome
dependent degradation of cdh1. This leads to a subsequent increase in glutaminase
(a degradation target of APC/C-Cdh1), which causes an elevation of glutamate
levels and further intraneuronal Ca(2+) dysregulation, resulting in neuronal
apoptosis. Glutaminase inhibition prevents glutamate excitotoxicity and apoptosis
in Abeta treated neurons. Furthermore, glutamate also decreases cdh1 and leads to
accumulation of glutaminase, suggesting that there may be a positive feedback
loop of cdh1 inactivation. We confirmed the main findings in vivo using
microinjection of either Abeta or glutamate in the CA1 region of the rat
hippocampus. We show here for the first time in vivo that both Abeta and
glutamate cause nuclear exclusion of cdh1 and an increase in glutaminase. These
results show that maintaining normal APC/C-Cdh1 activity may be a useful target
in Alzheimer's disease treatment.
PMID- 27514493
TI - Biosorption of Pb (II) from aqueous solution by extracellular polymeric
substances extracted from Klebsiella sp. J1: Adsorption behavior and mechanism
assessment.
AB - The adsorption performance and mechanism of extracellular polymeric substances
(EPS) extracted from Klebsiella sp. J1 for soluble Pb (II) were investigated. The
maximum biosorption capacity of EPS for Pb (II) was found to be 99.5 mg g(-1) at
pH 6.0 and EPS concentration of 0.2 g/L. The data for adsorption process
satisfactorily fitted to both Langmuir isotherm and pseudo-second order kinetic
model. The mean free energy E and activation energy Ea were determined at 8.22-
8.98 kJ mol(-1) and 42.46 kJ mol(-1), respectively. The liquid-film diffusion
step might be the rate-limiting step. The thermodynamic parameters (DeltaG(o),
DeltaH(o) and DeltaS(o)) revealed that the adsorption process was spontaneous and
exothermic under natural conditions. The interactions between EPS system and Pb
(II) ions were investigated by qualitative analysis methods (i.e Zeta potential,
FT-IR and EDAX). Based on the strong experimental evidence from the mass balance
of the related elements participating in the sorption process, an ion exchange
process was identified quantitatively as the major mechanism responsible for Pb
(II) adsorption by EPS. Molar equivalents of both K(+) and Mg(2+) could be
exchanged with Pb(2+) molar equivalents in the process and the contribution rate
of ion exchange to adsorption accounted for 85.72% (Deltamequiv = -0.000541).
PMID- 27514494
TI - Enhanced proliferation and differentiation effects of a CGRP- and Sr-enriched
calcium phosphate cement on bone mesenchymal stem cells.
AB - INTRODUCTION: Because of its good osteoconductivity, strontium (Sr) ranelate has
been extensively used as a bone substitute for the treatment of bone disorders.
To facilitate treatment, Sr is also incorporated into calcium phosphate cement
(Sr-CPC); however, the Sr from Sr-CPC is not sufficient to induce a significant
increase of bone mass in an ovariectomized rat model. To improve the efficiency
of Sr-CPC, we developed a calcitonin gene-related peptide (CGRP)- and Sr-enriched
CPC (CGRP-Sr-CPC). METHODS: We used X-ray diffraction and Fourier transform
infrared spectroscopy to measure properties of CGRP-Sr-CPC. We also employed a
cell proliferation assay, alkaline phosphatase (ALP) assay and real-time PCR to
assess the effects of CPC implants on proliferation and differentiation of bone
mesenchymal stem cells (BMSCs) from an ovariectomized rat model. RESULTS: CGRP
did not change the composition, pore sizes and compressive strength of the cement
body as compared with Sr-CPC. Meanwhile, CGRP-Sr-CPC did not show cell
cytotoxicity to BMSCs. Further, CGRP and Sr released from CGRP-Sr-CPC
significantly enhanced the cell proliferation of BMSCs and increased the activity
of ALP during differentiation of BMSCs, compared with CGRP- or Sr-CPC. Moreover,
CGRP-Sr-CPC significantly up-regulated the expression levels of osteogenic
differentiation-related genes including Alp, Bmp2, Osteonectin and Runx2 during
differentiation. CONCLUSIONS: These findings demonstrate the optimized effects of
CGRP- and Sr-enriched CPC in promoting proliferation and osteogenic
differentiation of BMSCs, suggesting the potential ability of this novel cement
to assist the formation of new bone during osteoporosis-induced bone disorders.
PMID- 27514496
TI - Elucidating the anti-Staphylococcus aureus antibody response by immunoproteomics.
AB - Staphylococcus aureus is a notorious pathogen both in- and outside hospitals as
well as a frequent colonizer in healthy individuals. Immunoproteomics techniques
have been employed to shed light on the human adaptive immune response to S.
aureus in health and disease. Since priming of immune memory, a key property of
the adaptive immune system, is the basis of successful vaccination,
immunoproteomics holds promise for paving the way to an effective S. aureus
vaccine.
PMID- 27514495
TI - Use of autologous epithelium transplantation on various scaffolds to cover tissue
loss in oral cavity: long-term observation.
AB - BACKGROUND: The aim of this study was to investigate the application of mucous
membrane keratinocyte cultures on amniotic membrane and on poly(L-lactic acid)
(PLLA) Purasorb PL38 to cover tissue loss in the oral cavity. Developments in
molecular biology techniques and tissue engineering allow the culturing and
identification of cells that can be anchored in the wound to achieve integrity of
the tissue. Transplantation of tissues obtained from the patient's own cells is
superior to allogenous transplantation where there is a possibility of
transfection, rejection and the need for long-term immunosuppression. METHODS: In
9 patients (15 procedures) keratinocytes cultured on amniotic membrane and PLLA
were transplanted to cover antro-oral fistulas and bone loss after
osteoradionecrosis. RESULTS: In all 6 patients with outlasting antro-oral
fistulas, the defects were healed. In 3 patients with 5 cases of tissue loss
after osteoradionecrosis, we obtained healing of the wound in only 1 case.
Histological examination of the cultures indicated that cultured cells formed
well-differentiated layers, very similar to the keratinocytes of mucous
membranes, although those seeded on amniotic membrane formed a single layer of
cells, while those seeded on the PLLA scaffold were arranged on 2 or more layers:
these differences were shown to be statistically significant with a morphometric
analysis. CONCLUSIONS: Autologous transplants of epithelium cultured on amniotic
membrane and PLLA constitute a new and effective way of covering nonhealing
tissue loss in the oral cavity in chosen cases, using modern methods of tissue
engineering.
PMID- 27514497
TI - An integrated approach to infer dynamic protein-gene interactions - A case study
of the human P53 protein.
AB - Investigating the dynamics of genetic regulatory networks through high throughput
experimental data, such as microarray gene expression profiles, is a very
important but challenging task. One of the major hindrances in building detailed
mathematical models for genetic regulation is the large number of unknown model
parameters. To tackle this challenge, a new integrated method is proposed by
combining a top-down approach and a bottom-up approach. First, the top-down
approach uses probabilistic graphical models to predict the network structure of
DNA repair pathway that is regulated by the p53 protein. Two networks are
predicted, namely a network of eight genes with eight inferred interactions and
an extended network of 21 genes with 17 interactions. Then, the bottom-up
approach using differential equation models is developed to study the detailed
genetic regulations based on either a fully connected regulatory network or a
gene network obtained by the top-down approach. Model simulation error, parameter
identifiability and robustness property are used as criteria to select the
optimal network. Simulation results together with permutation tests of input gene
network structures indicate that the prediction accuracy and robustness property
of the two predicted networks using the top-down approach are better than those
of the corresponding fully connected networks. In particular, the proposed
approach reduces computational cost significantly for inferring model parameters.
Overall, the new integrated method is a promising approach for investigating the
dynamics of genetic regulation.
PMID- 27514498
TI - Steroids can reduce warm ischemic reperfusion injury in a porcine donation after
circulatory death model with ex vivo lung perfusion evaluation.
AB - Donation after circulatory death (DCD) is being used to increase the number of
transplantable organs. The role and timing of steroids in DCD donation and ex
vivo lung perfusion (EVLP) has not been thoroughly investigated. In this study,
we investigated the effect of steroids on warm ischemic injury in a porcine model
(n = 6/group). Following cardiac arrest, grafts were left untouched in the donor
(90-min warm ischemia). Graft function was assessed after 6 h of EVLP. In the MP
group, 500 mg methylprednisolone was given prior to cardiac arrest and during
EVLP. In the CONTR group, no steroids were added. Median lung compliance (13
ml/cmH2 0) was significantly better preserved in the CONTR group than in the MP
group (30.5 ml/cmH2 0). Also, median wet-to-dry weight (6.11 vs. 6.94) and CT
density (182.5 vs. 352.9 g/l) were significantly better in the MP group than in
the CONTR group, respectively. There was no difference in oxygenation and
pulmonary vascular resistance. Perfusate cytokine analysis showed a significant
reduction in IL-1beta, IL-8, IFN-alpha, IL-10, TNF-alpha, and IFN-gamma in MP.
Cytokines in bronchoalveolar lavage were not decreased except for IFN-gamma. We
demonstrated that warm ischemic injury in DCD donation can be attenuated by
steroids when given prior to warm ischemia and during EVLP. Ethical context of
donor preconditioning should be discussed further.
PMID- 27514500
TI - Desymmetrizing Electron-Deficient Diboranes(4): Diverse Products and Their
Reactivity.
AB - A comprehensive study of the reactivity of Lewis bases with dihalodiboranes(4) is
presented. Diaryldihalodiboranes provide rearranged monoadducts when treated with
cyclic (alkyl)(amino)carbenes, but halide-bridged adducts when treated with a
range of pyridyl bases. Alternatively, the combination of diaminodihalodiboranes
with strong carbene donors leads to boraborenium salts. The reduction and halide
abstraction reactivity of these adducts was also explored, leading to
intramolecular C-H activation and the first 1,2-bis(borenium) dication.
PMID- 27514499
TI - Prognostic value of renal function in patients with aortic stenosis treated with
transcatheter aortic valve replacement.
AB - OBJECTIVES: The objectives of the present study were to analyze the variation of
renal function after transcatheter aortic valve replacement (TAVR) focused on
acute kidney injury (AKI) and its impact on short- and mid-term mortality.
BACKGROUND: Changes on renal function after TAVR and their impact on clinical
outcomes are incompletely understood until now. METHODS: At two tertiary centers
221 consecutive patients were submitted to TAVR. Kidney injury was defined
according to VARC-2 criteria. Patients were classified according to the presence
(group 1) or absence (group 2) of AKI. Creatinine values were collected daily
until seventh day after procedure, 1 month, 6 months, and then 1 year after TAVR.
RESULTS: At baseline, groups were similar, except for EuroSCORE II (8.66% vs.
7.34%, P = 0.02) and glomerular filtration rate (GFR) (39.59 vs. 48.49
mL/min.1.73 m2 , P = 0.002). Overall 30 day-mortality and 1-year mortality were
6.3% and 14.0%, respectively. Both 30-day mortality (23.1% vs. 1.2%, P < 0.001)
and 1-year mortality (44.2% vs. 4.7%, P < 0.001) were higher in group 1. After
multivariable-adjusted models, the only independent predictor for AKI after TAVR
was baseline GFR (HR: 1.37, 95% CI: 1.08-1.77, P = 0.01). The independent risk
factors for 1-year mortality were AKI (HR: 15.66, 95% CI: 6.07-44.63, P < 0.001),
COPD (HR: 3.14, 95% CI: 1.05-9.40, P = 0.04) and aortic regurgitation grade
postprocedure >= 2 (P = 0.05) also after multivariate analysis. CONCLUSIONS: In
this TAVR cohort, baseline GFR was the only independent predictor of AKI, which
negatively impacted on 30-day and 1-year mortality. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27514501
TI - Ion-Pair Complexation with Dibenzo[21]Crown-7 and Dibenzo[24]Crown-8 bis-Urea
Receptors.
AB - Synthesis and ion-pair complexation properties of novel ditopic bis-urea
receptors based on dibenzo[21]crown-7 (R(1) ) and dibenzo[24]crown-8 (R(2) )
scaffolds have been studied in the solid state, solution, and gas phase. In a 4:1
CDCl3 /[D6 ]DMSO solution, both receptors clearly show positive heterotropic
cooperativity toward halide anions when complexed with Rb(+) or Cs(+) , with the
halide affinity increasing in order I(-)
= 3 months was 19.6 % (95 % CI 14.6 % to 24.6 %) with a mean +/- SD
duration of pain of 6 . 5 +/- 5 . 7 years and a higher prevalence for women. The
prevalence of neuropathic pain in the respondents reporting chronic pain was 19 .
7 % (95 % CI 14 . 6-24 . 7), equivalent to 3 . 9 % (95 % CI 2 . 8 to 5 . 0 %) of
the general adult population. Only, 71 (29 . 8 %) of respondents reported that
their pain was being adequately controlled. CONCLUSIONS: The prevalence of
chronic pain in the general adult population of Libya was approximately 20 % and
comparable with Europe and North America. This suggests that chronic pain is a
public health problem in Libya. Risk factors are being a woman, advanced age and
unemployment. There is a need for improved health policies in Libya to ensure
that patients with chronic pain receive effective management.
PMID- 27514514
TI - Continued efforts to translate diabetes cardiovascular outcome trials into
clinical practice.
AB - Diabetic patients suffer from a high rate of cardiovascular events and such risk
increases with HbA1c. However, lowering HbA1c does not appear to yield the same
benefit on macrovascular endpoints, as observed for microvascular endpoints. As
the number of glucose-lowering medications increases, clinicians have to consider
several open questions in the management of type 2 diabetes, one of which is the
cardiovascular risk profile of each regimen. Recent placebo-controlled
cardiovascular outcome trials (CVOTs) have responded to some of these questions,
but careful interpretation is needed. After general disappointment around CVOTs
assessing safety of DPP-4 inhibitors (SAVOR, TECOS, EXAMINE) and the GLP-1
receptor agonist lixisenatide (ELIXA), the EMPA-REG Outcome trial and the LEADER
trial have shown superiority of the SGLT2-I empagliflozin and the GLP-1RA
liraglutide, respectively, on the 3-point MACE outcome (cardiovascular death, non
fatal myocardial infarction or stroke) and cardiovascular, as well as all-cause
mortality. While available mechanistic studies largely support a cardioprotective
effect of GLP-1, the ability of SGLT2 inhibitor(s) to prevent cardiovascular
death was unexpected and deserves future investigation. We herein review the
results of completed CVOTs of glucose-lowering medications and suggest a possible
treatment algorithm based on cardiac and renal co-morbidities to translate CVOT
findings into clinical practice.
PMID- 27514515
TI - Chronic viral hepatitis: policy, regulation, and strategies for its control and
elimination in Ethiopia.
AB - BACKGROUND: Hepatitis B and C are silent killers not yet recognized as major
public health challenges in many developing countries with huge disease burden.
In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the
prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is
likely to be underreported due to the lack of diagnostic facilities and
appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara
African countries lacking a coordinated and systematic national response to
chronic viral hepatitis. The objective of this study is to examine the current
level of response to viral Hepatitis B & C in Ethiopia with the aim to bring
identified gaps to the attention of relevant stakeholders and policy makers.
METHODS: This cross-sectional qualitative study was based on semi-structured in
depth interviews with 21 key informants from health facilities, health offices,
pharmaceutical companies, regulatory bodies, professional association and blood
bank units. Participants were selected purposively based on their role in the
national hepatitis response. The investigators also reviewed available policy and
strategy documents, standards of practice and surveys, and paid visits to
pharmaceutical premises to check the availability of antiviral drugs. Thematic
analysis was employed to make sense of the data. During the data analysis
process, all the authors critically read the materials, and data was triangulated
by source, interpreter view and thematic perspective to ensure accurate
representation and comprehensiveness, and validation of the interviewees'
responses. Once each investigator reviewed the data independently, the team
reached a common understanding of the scope and contexts of the information
attained. Data were subsequently reduced to key concepts, and case stories were
taken with successive revisions. The key concepts were later coded into most
basic meaningful categories. The World Health Organization (WHO) global hepatitis
response framework was used to organize the analysis. RESULTS: Ethiopia is in the
process of preparing strategic plan and guidelines for viral hepatitis. However,
the country still lacks the required partnerships, and resource mobilization as a
national health response is limited. Community awareness on the disease
transmission and its sequel is poor. Viral hepatitis screening services are not
widely available except for the occasional mandatory medical checkups for work or
travel purposes. Healthcare providers often take no further action after
diagnosing patients with viral hepatitis due to lack of treatment guidelines and
strategic frameworks for screening, diagnosis, and treatment. Besides, drugs that
are effective in the treatment of viral hepatitis are not available, mainly due
to regulatory challenges. CONCLUSIONS: Viral hepatitis and its disease burden are
getting little attention in Ethiopia and many low-income countries. The levels of
technical guidance and financial support from the international community are
low. To date, the response to the infections in Ethiopia is patchy. Thus, the
country needs to formulate policy and strategies in the areas of disease
surveillance, risk group identification and screening, use of the birth dose of
hepatitis B vaccine, and care and treatment. Improving availability of data on
viral hepatitis, access to low-cost generic drugs and developing and
dissemination of treatment guidelines are also critical. Leveraging the
successful Health Extension Program for a hepatitis response, and exploring ways
to learn from and integrate into the HIV/AIDS program should also be considered.
PMID- 27514516
TI - Transcriptional profiling analysis of Penicillium digitatum, the causal agent of
citrus green mold, unravels an inhibited ergosterol biosynthesis pathway in
response to citral.
AB - BACKGROUND: Green mold caused by Penicillium digitatum is the most damaging
postharvest diseases of citrus fruit. Previously, we have observed that citral
dose-dependently inhibited the mycelial growth of P. digitatum, with the minimum
inhibitory concentration (MIC) of 1.78 mg/mL, but the underlying molecular
mechanism is barely understood. RESULTS: In this study, the transcriptional
profiling of the control and 1/2MIC-citral treated P. digitatum mycelia after 30
min of exposure were analyzed by RNA-Seq. A total of 6355 genes, including 2322
up-regulated and 4033 down-regulated genes, were found to be responsive to
citral. These genes were mapped to 155 KEGG pathways, mainly concerning mRNA
surveillance, RNA polymerase, RNA transport, aminoacyl-tRNA biosynthesis, ABC
transporter, glycolysis/gluconeogenesis, citrate cycle, oxidative
phosphorylation, sulfur metabolism, nitrogen metabolism, inositol phosphate
metabolism, fatty acid biosynthesis, unsaturated fatty acids biosynthesis, fatty
acid metabolism, and steroid biosynthesis. Particularly, citral exposure affected
the expression levels of five ergosterol biosynthetic genes (e.g. ERG7, ERG11,
ERG6, ERG3 and ERG5), which corresponds well with the GC-MS results, the
reduction in ergosterol content, and accumulation of massive lanosterol. In
addition, ERG11, the gene responsible for lanosterol 14alpha-demethylase, was
observed to be the key down-regulated gene in response to citral. CONCLUSION: Our
present finding suggests that citral could exhibit its antifungal activity
against P. digitatum by the down-regulation of ergosterol biosynthesis.
PMID- 27514517
TI - Evolution of the locomotory system in eels (Teleostei: Elopomorpha).
AB - BACKGROUND: Living anguilliform eels represent a distinct clade of elongated
teleostean fishes inhabiting a wide range of habitats. Locomotion of these fishes
is highly influenced by the elongated body shape, the anatomy of the vertebral
column, and the corresponding soft tissues represented by the musculotendinous
system. Up to now, the evolution of axial elongation in eels has been inferred
from living taxa only, whereas the reconstruction of evolutionary patterns and
functional ecology in extinct eels still is scarce. Rare but excellently
preserved fossil eels from the Late Cretaceous and Cenozoic were investigated
here to gain a better understanding of locomotory system evolution in
anguilliforms and, consequently, their habitat occupations in deep time. RESULTS:
The number of vertebrae in correlation with the body length separates extinct and
extant anguilliforms. Even if the phylogenetic signal cannot entirely be
excluded, the analyses performed here reveal a continuous shortening of the
vertebral column with a simultaneous increase in vertebral numbers in conjunction
with short lateral tendons throughout the order. These anatomical changes
contradict previous hypotheses based on extant eels solely. CONCLUSIONS: The body
curvatures of extant anguilliforms are highly flexible and can be clearly
distinguished from extinct species. Anatomical changes of the vertebral column
and musculotendinous system through time and between extinct and extant
anguilliforms correlate with changes of the body plan and swimming performance
and reveal significant shifts in habitat adaptation and thus behaviour.
Evolutionary changes in the skeletal system of eels established here also imply
that environmental shifts were triggered by abiotic rather than biotic factors
(e.g., K/P boundary mass extinction event).
PMID- 27514519
TI - [Epidemiology of common diseases in ophthalmology].
PMID- 27514518
TI - Minimally invasive surgery using intraoperative electron-beam radiotherapy for
the treatment of soft tissue sarcoma of the extremities with tendon involvement.
AB - BACKGROUND: When a soft tissue sarcoma (STS) is located at the distal part of an
extremity and involves the tendon, a wide excision usually causes severe
functional disability. We therefore developed a minimally invasive surgical
technique using intraoperative electron-beam radiotherapy (IOERT) to reduce the
incidence of post-operative functional disability in patients with peri-/intra
tendinous STS. We assessed the clinical outcomes of the novel minimally invasive
surgery. METHODS: The study population included five patients who received
treatment for distal extremity STSs. After elevating the tumor mass, including
the tendon and nerve from the tumor bed with a wide margin, a lead board was
inserted beneath the tumor mass to shield the normal tissue. IOERT (25-50 Gy) was
then applied, and the tumor excised with care taken to maintain the continuity of
the tendon. RESULTS: In a desmoid patient, local recurrence was observed outside
the irradiated field. No cases of neuropathy or bone necrosis were observed. The
mean limb function score was excellent in all patients. None of the high-grade
sarcoma patients had local recurrence or distant metastasis. CONCLUSIONS:
Although the current study is only a pilot study with a small number of patients,
it shows that this minimally invasive procedure has the potential to become a
standard treatment option for selected patients. TRIAL REGISTRATION: H17-250
(registered 2 November 2005) and H25-250 (modified from H17-250, registered 5
December 2013).
PMID- 27514520
TI - [Cherry-red spot in a 13-month-old child].
PMID- 27514521
TI - [Atypical wet AMD].
PMID- 27514522
TI - [Optic disc pit-associated maculopathy and iris-retinochoroidal-coloboma - a rare
combination].
AB - Kranenburg's syndrome is defined as central serous detachment associated with an
optic disc pit. We report the interesting and very seldom combination of
Kranenburg's syndrome and iris-retinochoroidal-coloboma. Reattachment was
achieved after vitrectomy, peeling of epiretinal membranes, laser coagulation
adjacent and temporal to the optic disc and gas endotamponade. Coincidence of
this syndrome with an iris-retinochoroidal-coloboma is extremely rare. Both
coloboma and optic disc pit are based on closure defects during week 6 of
embryogenesis.
PMID- 27514523
TI - Kikiskawawasow - prenatal healthcare provider perceptions of effective care for
First Nations women: an ethnographic community-based participatory research
study.
AB - BACKGROUND: Pregnant Indigenous women suffer a disproportionate burden of risk
and adverse outcomes relative to non-Indigenous women. Although there has been a
call for improved prenatal care, examples are scarce. Therefore, we explored the
characteristics of effective care with First Nations women from the perspective
of prenatal healthcare providers (HCPs). METHODS: We conducted an ethnographic
community-based participatory research study in collaboration with a large Cree
First Nations community in Alberta, Canada. We carried out semi-structured
interviews with 12 prenatal healthcare providers (HCPs) that were recorded,
transcribed, and subjected to qualitative content analysis. RESULTS: According to
the participants, relationships and trust, cultural understanding, and context
specific care were key features of effective prenatal care and challenge the
typical healthcare model. HCPs that are able to foster sincere, non-judgmental,
and enjoyable interactions with patients may be more effective in treating
pregnant First Nations women, and better able to express empathy and
understanding. Ongoing HCP cultural understanding specific to the community
served is crucial to trusting relationships, and arises from real experiences and
learning from patients over and above relying only on formal cultural sensitivity
training. Consequently, HCPs report being better able to adapt a more flexible,
all-inclusive, and accessible approach that meets specific needs of patients.
CONCLUSIONS: Aligned with the recommendations of the Truth and Reconciliation
Commission of Canada, improving prenatal care for First Nations women needs to
allow for genuine relationship building with patients, with enhanced and
authentic cultural understanding by HCPs, and care approaches tailored to women's
needs, culture, and context.
PMID- 27514524
TI - Quercetin and Cisplatin combined treatment altered cell cycle and mitogen
activated protein kinase expressions in malignant mesotelioma cells.
AB - BACKGROUND: Malignant mesothelioma is a locally aggressive and highly lethal
neoplasm of pleural, peritoneal and pericardial mesothelial cells without
successful therapy. Previously, we reported that Quercetin in combination with
Cisplatin inhibits cell proliferation and activates caspase-9 and -3 enzymes in
different malignant mesothelioma cell lines. Moreover, Quercetin + Cisplatin lead
to accumulation of both SPC111 and SPC212 cell lines in S phase. METHODS: In
present work, 84 genes involved in cell growth and proliferation have analysed by
using RT(2)-PCR array system and protein profile of mitogen activated protein
kinase (MAPK) family proteins investigated by western blots. RESULTS: Our results
showed that Quercetin and Quercetin + Cisplatin modulated gene expression of
cyclins, cyclin dependent kinases and cyclin dependent kinases inhibitors. In
addition genes involved in JNK, p38 and MAPK/ERK pathways were up regulated.
Moreover, while p38 and JNK phosphorylations were increased, ERK phosphorylations
were decreased after using Quercetin + Cisplatin. CONCLUSION: This research has
clarified our previous results and detailed mechanism of anti-carcinogenic
potential of Quercetin alone and incombination with Cisplatin on malignant
mesothelioma cells.
PMID- 27514525
TI - Downregulation of KDM4A Suppresses the Survival of Glioma Cells by Promoting
Autophagy.
AB - Glioma is the most common type of primary intracranial tumor and has a poor
prognosis. It has been reported that lysine-specific demethylase 4A (KDM4A) can
promote tumor progression; however, its role in human glioma remains unclear.
Western blot and qRT-PCR analyses showed that KDM4A was highly expressed in U87MG
and T98G cells. 48 h after transfection with siKDM4A, the protein level of KDM4A
was significantly downregulated. The silenced expression of KDM4A in T98G or
U87MG cells inhibited cell viability and invasion, and aggravated cell apoptosis.
We found that the siKDM4A led to a significant increase in acidic vesicular
organelles (AVOs) and upregulated the expression of autophagy-related proteins,
including LC3B-phosphatidylethanolamine conjugate, a cytosolic form of LC3B (LC3B
II/LC3B-I) and Beclin 1 in T98G and U87MG cells. Further studies demonstrated
that after pretreatment with 3-MA (3 mmol/L) for 48 h, siKDM4A-transfected cells
showed a prominent decrease in LC3B-II/LC3B-I and Beclin 1, accompanied by
increased viability and invasion and decreased apoptosis. Our results suggest
that the inhibition of KDM4A expression might efficiently suppress glioma cell
survival by promoting autophagy, providing a promising agent for treating
malignant gliomas.
PMID- 27514527
TI - Strategy based on kinetics of O-(2-[18F] fluoroethyl)-L-tyrosine ([18F] FET).
PMID- 27514526
TI - A Conceptualization of the Utility of Subjective Cognitive Decline in Clinical
Trials of Preclinical Alzheimer's Disease.
AB - This commentary outlines a conceptual model for subjective cognitive decline
(SCD) in relation to Alzheimer's disease (AD) biomarkers in the preclinical
stages of disease and a framework for effectively utilizing SCD in secondary
prevention clinical trials. Mounting evidence supports the notion that SCD is
sensitive to encroaching Abeta-amyloid and neurodegeneration. SCD has also been
shown to provide additive information of AD-dementia risk beyond what is known
about the biomarker status of the individual. Thus, we provide recommendations
for the implementing SCD measurement in clinical trials. We argue that SCD can be
measured at three catch points within the course of the clinical trial: firstly,
at the initial recruitment and screening phase; secondly, to create more robust
estimates of rates of AD-dementia progression; and finally, to measure subjective
experiences of cognitive change and quality of life over the course of the trial
as a proxy of clinically meaningful functional improvement. We provide
recommendations of how SCD can be approached at each of these points. SCD is an
important component of the preclinical AD-dementia trajectory. Future studies
need to elucidate the interactive influence of Abeta-amyloid and tau on SCD from
a spatiotemporal perspective. Even as this evidence accrues, it is clear that SCD
can provide unique and additive information about rates of progression and
subjectively experienced cognitive change within clinical trials.
PMID- 27514529
TI - Saccharibacillus qingshengii sp. nov., isolated from a lead-cadmium tailing.
AB - A Gram-stain-positive, strictly aerobic strain, H6T, was isolated from a soil
sample of lead-cadmium tailing in Qixia district, Nanjing (China). Cells of the
strain are rod-shaped and colonies on LB agar are red. Strain H6T has subpolar
and polar flagella and the optimal condition for growth is 30 degrees C, with 1
% (w/v) NaCl and at pH 7.0. Based on the 16S rRNA gene sequences, phylogenetic
analysis showed that strain H6T was closely related to the genus
Saccharibacillus, and the closest relatives were Saccharibacillus deserti WLJ055T
(99.0 % 16S rRNA gene sequence similarity), Saccharibacillus kuerlensis HR1T
(97.0 %) and Saccharibacillus sacchari GR21T (96.4 %). The DNA-DNA relatedness
value between strain H6T and S. deserti WLJ055T was 55.0 %. The major polar
lipids of strain H6T were diphosphatidylglycerol, phosphatidylglycerol,
phosphoglycolipid and three unknown glycolipids. The DNA G+C content was 58.4
mol% and MK-7 was the major isoprenoid quinone. The major fatty acids were
anteiso-C15 : 0 and C16 : 0. meso-Diaminopimelic acid was detected in the
peptidoglycan. Based on the phylogenetic, biochemical and chemotaxonomic data,
strain H6T represents a novel species of the genus Saccharibacillus, for which
the name Saccharibacillus qingshengii sp. nov., is proposed. The type strain is
H6T (=CCTCC AB 2016001T=JCM 31172T).
PMID- 27514528
TI - Guidelines to PET measurements of the target occupancy in the brain for drug
development.
AB - This guideline summarizes the current view of the European Association of Nuclear
Medicine Drug Development Committee. The purpose of this guideline is to
guarantee a high standard of PET studies that are aimed at measuring target
occupancy in the brain within the framework of development programs of drugs that
act within the central nervous system (CNS drugs). This guideline is intended to
present information specifically adapted to European practice. The information
provided should be applied within the context of local conditions and
regulations.
PMID- 27514530
TI - Over-expression of long noncoding RNA BANCR inhibits malignant phenotypes of
human bladder cancer.
AB - BACKGROUND: Accumulating evidences indicated that lncRNAs play crucial regulatory
roles in oncogenesis and progression of cancers. BRAF activated non-coding RNA
(BANCR) has been identified to contribute to the progression of some human
cancers. However, the relationship between BANCR and bladder cancer (BC) is
largely unclear. METHODS: BANCR expression levels in BC, paired non-cancer
tissues and BC cell lines were detected by real-time quantitative RT-PCR (qRT
PCR). The relationships between BANCR expression levels and the clinical
characteristics were evaluated. BANCR expression was enhanced by transfecting a
pcDNA-BANCR vector. We used both CCK-8 assay and Edu assay to detect cell
proliferation. We also detect cell apoptosis and migration by using ELISA assay,
Flow cytometry and transwell assay, respectively. All statistical analyses were
executed by using the SPSS 20.0 software. RESULTS: BANCR expression levels were
remarkably decreased in BC tissues compared with adjacent noncancerous tissues.
BANCR expression levels in two BC cell lines were also significantly down
regulated. Clinicopathologic analysis revealed that low BANCR expression was
positively correlated with TNM stage, but not associated with other
clinicopathological characteristics. BANCR has been successfully overexpressed in
BC cell lines (T24 and SW780) by transfecting a pcDNA-BANCR vector. Cell
proliferation inhibition, apoptosis induction and migration suppression were also
observed in pCDNA-BANCR-transfected T24 and SW780 cells. CONCLUSIONS: These data
suggested that BANCR represents a tumor suppressor player in bladder cancer,
contributes to tumor proliferation, apoptosis and migration, and may serve as a
new candidate biomarker and a potential therapeutic target for patients with BC.
PMID- 27514531
TI - Metabolic signatures and risk of type 2 diabetes in a Chinese population: an
untargeted metabolomics study using both LC-MS and GC-MS.
AB - AIMS/HYPOTHESIS: Metabolomics has provided new insight into diabetes risk
assessment. In this study we characterised the human serum metabolic profiles of
participants in the Singapore Chinese Health Study cohort to identify metabolic
signatures associated with an increased risk of type 2 diabetes. METHODS: In this
nested case-control study, baseline serum metabolite profiles were measured using
LC-MS and GC-MS during a 6-year follow-up of 197 individuals with type 2 diabetes
but without a history of cardiovascular disease or cancer before diabetes
diagnosis, and 197 healthy controls matched by age, sex and date of blood
collection. RESULTS: A total of 51 differential metabolites were identified
between cases and controls. Of these, 35 were significantly associated with
diabetes risk in the multivariate analysis after false discovery rate adjustment,
such as increased branched-chain amino acids (leucine, isoleucine and valine),
non-esterified fatty acids (palmitic acid, stearic acid, oleic acid and linoleic
acid) and lysophosphatidylinositol (LPI) species (16:1, 18:1, 18:2, 20:3, 20:4
and 22:6). A combination of six metabolites including proline, glycerol,
aminomalonic acid, LPI (16:1), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid
and urea showed the potential to predict type 2 diabetes in at-risk individuals
with high baseline HbA1c levels (>=6.5% [47.5 mmol/mol]) with an AUC of 0.935.
Combined lysophosphatidylglycerol (LPG) (12:0) and LPI (16:1) also showed the
potential to predict type 2 diabetes in individuals with normal baseline HbA1c
levels (<6.5% [47.5 mmol/mol]; AUC = 0.781). CONCLUSIONS/INTERPRETATION: Our
findings show that branched-chain amino acids and NEFA are potent predictors of
diabetes development in Chinese adults. Our results also indicate the potential
of lysophospholipids for predicting diabetes.
PMID- 27514533
TI - Src is required for migration, phagocytosis, and interferon beta production in
Toll-like receptor-engaged macrophages.
AB - As an evolutionarily conserved mechanism, innate immunity controls self-nonself
discrimination to protect a host from invasive pathogens. Macrophages are major
participants of the innate immune system. Through the activation of diverse Toll
like receptors (TLRs), macrophages are triggered to initiate a variety of
functions including locomotion, phagocytosis, and secretion of cytokines that
requires the participation of tyrosine kinases. Fgr, Hck, and Lyn are myeloid
specific Src family kinases. Despite their constitutively high expression in
macrophages, their absence does not impair LPS responsiveness. In contrast, Src,
a barely detectable tyrosine kinase in resting macrophages, becomes greatly
inducible in response to TLR engagement, implicating its role in macrophage
activation. Indeed, silencing Src suppresses the activated TLR-mediated
migration, phagocytosis, and interferon-beta (IFN-beta) secretion in macrophages.
And these physiological defects can be restored by the introduction of siRNA
resistant Src. Notably, the elevated expression and activity of Src is inducible
nitric oxide synthase (iNOS)-dependent. Due to (1) iNOS being a NF-kappaB target,
which can be induced by various TLR ligands, (2) Src can mediate NF-kappaB
activation, therefore, there ought to exist a loop of signal amplification that
regulates macrophage physiology in response to the engagement of TLRs.
PMID- 27514532
TI - IRS proteins and diabetic complications.
AB - IRS proteins are cellular adaptor molecules that mediate many of the key
metabolic actions of insulin. When tyrosine is phosphorylated by the activated
insulin receptor, IRS proteins recruit downstream effectors, such as
phosphoinositide 3-kinase and mitogen-activated protein kinase, in order to
elicit cellular responses such as glucose uptake, lipid metabolism and cell
proliferation. There are two main IRS proteins in humans (IRS1 and IRS2), both of
which are widely expressed. Given their central role in the insulin signalling
pathway, it is not surprising that male mice lacking Irs1 or Irs2 present with
elevated blood glucose or type 2 diabetes, respectively. For reasons yet to be
identified, female Irs2 (-/-) mice do not develop type 2 diabetes. A number of
organs are affected by complications of diabetes; macrovascular complications
include stroke and coronary artery disease, while nephropathy, neuropathy and
retinopathy fall into the category of microvascular complications. Given the
serious consequences of these complications on patient morbidity and mortality,
it is essential to identify the molecular pathogenesis underlying diabetic
complications, with a view to improving therapeutic intervention and patient
outcomes. A number of recently published papers have converged on the hypothesis
that the loss of insulin signalling and IRS proteins is instrumental to the
development and/or progression of diabetic complications. This review will
summarise some highlights from the published work in which this hypothesis is
discussed.
PMID- 27514534
TI - EPA or DHA enhanced oxidative stress and aging protein expression in brain of d
galactose treated mice.
AB - BACKGROUND: Effects of eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid
(DHA, 22:6) upon fatty acid composition, oxidative and inflammatory factors and
aging proteins in brain of d-galactose (DG) treated aging mice were examined.
METHODS: Each fatty acid at 7 mg/kg BW/week was supplied for 8 weeks. Brain aging
was induced by DG treatment (100 mg/kg body weight) via daily subcutaneous
injection for 8 weeks. RESULTS: DG, EPA and DHA treatments changed brain fatty
acid composition. DG down-regulated brain Bcl-2 expression and up-regulated Bax
expression. Compared with DG groups, EPA and DHA further enhanced Bax expression.
DG decreased glutathione content, increased reactive oxygen species (ROS) and
oxidized glutathione (GSSG) production, the intake of EPA or DHA caused greater
ROS and GSSG formation. DG treatments up-regulated the protein expression of
p47(phox) and gp91(phox), and the intake of EPA or DHA led to greater p47(phox)
and gp91(phox) expression. DG increased brain prostaglandin E2 (PGE2) levels, and
cyclooxygenase (COX)-2 expression and activity, the intake of EPA or DHA reduced
brain COX-2 activity and PGE2 formation. DG enhanced brain p53, p16 and p21
expression. EPA and DHA intake led to greater p21 expression, and EPA only caused
greater p53 and p16 expression. CONCLUSION: These findings suggest that these two
PUFAs have toxic effects toward aging brain.
PMID- 27514535
TI - Left subclavian artery-esophageal fistula induced by a paper star: a case report.
AB - A subclavian artery-esophageal fistula usually occurs on the right side of an
aberrant subclavian artery. It also rarely appears in the site between a non
aberrant subclavian artery and the esophagus due to the ingestion of a foreign
body. Upper gastrointestinal bleeding in the case of a subclavian artery
esophageal fistula is rare but often fatal. Here, we report on a 62-year-old male
patient with a left subclavian arteryesophageal fistula complicated by
hemorrhagic shock. He swallowed a foreign body at a birthday party. An upper
gastrointestinal endoscopy indicated a paper star lodged at 20 cm from the
incisors, inducing a kissing esophageal ulcer around the esophageal sphincter.
One month later, he suffered an unusually strong episode of hematemesis.
Subsequently, a computed tomography angiography was performed and demonstrated a
left subclavian artery-esophageal fistula. Finally, the fistula induced by the
ingestion of a paper star was successfully treated by endovascular stent
grafting.
PMID- 27514536
TI - SIRT1/Atg5/autophagy are involved in the antiatherosclerosis effects of ursolic
acid.
AB - The purpose of this study was to investigate the antiatherosclerosis effects of
ursolic acid (UA) in high-fat diet-fed quails (Coturnix coturnix) and potential
mechanism. Quails were treated with high-fat diet (14 % pork oil, 1 % cholesterol
w/w) with or without UA (50, 150, or 300 mg/kg/day) for 10 weeks. Serum lipid
profile was assessed at 0, 4.5, and 10 weeks. After 10 weeks, serum antioxidant
status and morphology of aorta were assessed. Additionally, human umbilical vein
endothelial cells (HUVECs) were exposed to 100 MUg/ml oxidized low-density
lipoprotein (ox-LDL) for 24 h, with or without pretreatment with UA (5, 10 or 20
MUM) for 16 h, autophagy inhibitor 3-MA 5 mM for 2 h, or SIRT1 inhibitor EX-527
10 MUM for 2 h. Cell viability and oxidative stress status were assessed and
autophagy status was determined. Acetylation of lysine residue on Atg5 was
assessed with immunoprecipitation. In results, high-fat diet negatively affected
serum lipid profile and antioxidant status in quails and induced significant
histological changes. Cotreatment with UA remarkably alleviated such changes. In
HUVECs, ox-LDL treatment induced significant cytotoxicity along with oxidative
stress, while UA cotreatment alleviated such changes significantly. UA treatment
induced autophagy, enhanced SIRT1 expression, and decreased acetylation of lysine
residue on Atg5. Cotreatment with 3-MA or EX-527 effectively abolished UA's
protective effects. In summary, UA exerted antiatherosclerosis effects in quails
and protected HUVECs from ox-LDL induced cytotoxicity, and the mechanism is
associated with increased SIRT1 expression, decreased Atg5 acetylation on lysine
residue, and increased autophagy.
PMID- 27514537
TI - CNTF-ACM promotes mitochondrial respiration and oxidative stress in cortical
neurons through upregulating L-type calcium channel activity.
AB - A specialized culture medium termed ciliary neurotrophic factor-treated astrocyte
conditioned medium (CNTF-ACM) allows investigators to assess the peripheral
effects of CNTF-induced activated astrocytes upon cultured neurons. CNTF-ACM has
been shown to upregulate neuronal L-type calcium channel current activity, which
has been previously linked to changes in mitochondrial respiration and oxidative
stress. Therefore, the aim of this study was to evaluate CNTF-ACM's effects upon
mitochondrial respiration and oxidative stress in rat cortical neurons. Cortical
neurons, CNTF-ACM, and untreated control astrocyte-conditioned medium (UC-ACM)
were prepared from neonatal Sprague-Dawley rat cortical tissue. Neurons were
cultured in either CNTF-ACM or UC-ACM for a 48-h period. Changes in the following
parameters before and after treatment with the L-type calcium channel blocker
isradipine were assessed: (i) intracellular calcium levels, (ii) mitochondrial
membrane potential (DeltaPsim), (iii) oxygen consumption rate (OCR) and adenosine
triphosphate (ATP) formation, (iv) intracellular nitric oxide (NO) levels, (v)
mitochondrial reactive oxygen species (ROS) production, and (vi) susceptibility
to the mitochondrial complex I toxin rotenone. CNTF-ACM neurons displayed the
following significant changes relative to UC-ACM neurons: (i) increased
intracellular calcium levels (p < 0.05), (ii) elevation in DeltaPsim (p < 0.05),
(iii) increased OCR and ATP formation (p < 0.05), (iv) increased intracellular NO
levels (p < 0.05), (v) increased mitochondrial ROS production (p < 0.05), and
(vi) increased susceptibility to rotenone (p < 0.05). Treatment with isradipine
was able to partially rescue these negative effects of CNTF-ACM (p < 0.05). CNTF
ACM promotes mitochondrial respiration and oxidative stress in cortical neurons
through elevating L-type calcium channel activity.
PMID- 27514538
TI - Mitoprotective antioxidant EUK-134 stimulates fatty acid oxidation and prevents
hypertrophy in H9C2 cells.
AB - Oxidative stress is an important contributory factor for the development of
cardiovascular diseases like hypertension-induced hypertrophy. Mitochondrion is
the major source of reactive oxygen species. Hence, protecting mitochondria from
oxidative damage can be an effective therapeutic strategy for the prevention of
hypertensive heart disease. Conventional antioxidants are not likely to be
cardioprotective, as they cannot protect mitochondria from oxidative damage. EUK
134 is a salen-manganese complex with superoxide dismutase and catalase activity.
The possible role of EUK-134, a mitoprotective antioxidant, in the prevention of
hypertrophy of H9C2 cells was examined. The cells were stimulated with
phenylephrine (50 MUM), and hypertrophy was assessed based on cell volume and
expression of brain natriuretic peptide and calcineurin. Enhanced myocardial
lipid peroxidation and protein carbonyl content, accompanied by nuclear factor
kappa B gene expression, confirmed the presence of oxidative stress in
hypertrophic cells. Metabolic shift was evident from reduction in the expression
of medium-chain acyl-CoA dehydrogenase. Mitochondrial oxidative stress was
confirmed by the reduced expression of mitochondria-specific antioxidant
peroxiredoxin-3 and enhanced mitochondrial superoxide production. Compromised
mitochondrial function was apparent from reduced mitochondrial membrane
potential. Pretreatment with EUK-134 (10 MUM) was effective in the prevention of
hypertrophic changes in H9C2 cells, reduction of oxidative stress, and prevention
of metabolic shift. EUK-134 treatment improved the oxidative status of
mitochondria and reversed hypertrophy-induced reduction of mitochondrial membrane
potential. Supplementation with EUK-134 is therefore identified as a novel
approach to attenuate cardiac hypertrophy and lends scope for the development of
EUK-134 as a therapeutic agent in the management of human cardiovascular disease.
PMID- 27514540
TI - Creep and stress relaxation of human red cell membrane.
AB - In contrast to most mechanical properties of the red cell, experimental
information on stress relaxation (SR) of the membrane skeleton is scarce. On the
other hand, many postulates or assumptions as to the value of the characteristic
time of SR [Formula: see text] can be found in the literature. Here, an
experiment is presented that allows measurement of [Formula: see text] up to
values of about 10 h. The membrane skeleton was deformed passively by changing
the spontaneous curvature of the bilayer thus transforming the natively biconcave
red cells into echinocytes. This shape and the concomitant deformation of the
skeleton were kept up to 4 h by incubation at 37 C. During this period, no
plastic deformation (creep) was observed. After the incubation, the spontaneous
curvature was returned to normal. The resulting shape was smooth showing no
remnants of the echinocytic shape. Both observations indicate [Formula: see text]
10 h. This result is in gross disagreement to postulates or assumptions existing
in the literature.
PMID- 27514539
TI - Implementation of 2011 Duty Hours Regulations through a Workload Reduction
Strategy and Impact on Residency Training.
AB - BACKGROUND: Training programs have implemented the 2011 ACGME duty hour
regulations (DHR) using "workload compression" (WLC) strategies, attempting to
fit similar clinical responsibilities into fewer working hours, or workload
reduction (WLR) approaches, reducing the number of patient encounters per
trainee. Many have expressed concern that these strategies could negatively
impact patient care and learner outcomes. OBJECTIVE: This study evaluates the
medical knowledge and clinical impact of a WLR intervention in a single
institution. DESIGN & PARTICIPANTS: Nonrandomized intervention study with
comparison to a historical control study among 58 PGY-1 internal medicine
trainees in the 2 years after duty hour implementation [exposure cohort (EC),
7/1/2011-6/30/2013], compared to 2 years before implementation [comparison cohort
(CC), 7/1/2009-6/30/2011]. MAIN MEASURES: Process outcomes were average inpatient
encounters, average new inpatient admissions, and average scheduled outpatient
encounters per PGY-1 year. Performance outcomes included trainee inpatient and
outpatient days on service, In-Training Examination (ITE) scores as an objective
surrogate of medical knowledge, Case-Mix Index (CMI), and quality of care
measures (30-day readmission rate, 30-day mortality rate, and average length of
stay). KEY RESULTS: Baseline characteristics and average numbers of inpatient
encounters per PGY-1 class were similar between the EC and CC. However, the EC
experienced fewer new inpatient admissions (157.47 +/- 40.47 vs. 181.72 +/-
25.45; p < 0.01), more outpatient encounters (64.80 +/- 10.85 vs. 56.98 +/- 6.59;
p < 0.01), and had similar ITE percentiles (p = 0.58). Patients of similar
complexity cared for by the EC also had a greater reduction in readmissions
(21.21 % to 19.08 %; p < 0.01) than the hospital baseline (12.07 to 11.14 %; p <
0.01). CONCLUSIONS: Our WLR resulted in a small decrease in the average number of
new inpatient admissions and an increase in outpatient encounters. ITE and care
quality outcomes were maintained or improved. While there is theoretical concern
that reducing PGY-1 inpatient admissions volumes may negatively impact education
and clinical care measures, this study found no evidence of such a trade-off.
PMID- 27514541
TI - The effect of loading rate on the development of early damage in articular
cartilage.
AB - Experimental reports suggest that cartilage damage depends on strain magnitude.
Additionally, because of its poro-viscoelastic nature, strain magnitude in
cartilage can depend on strain rate. The present study explores whether cartilage
damage may develop dependent on strain rate, even when the presented damage
numerical model is strain-dependent but not strain-rate-dependent. So far no
experiments have been distinguished whether rate-dependent cartilage damage
occurs in the collagen or in the non-fibrillar network. Thus, this research
presents a finite element analysis model where, among others, collagen and non
fibrillar matrix are incorporated as well as a strain-dependent damage mechanism
for these components. Collagen and non-fibrillar matrix stiffness decrease when a
given strain is reached until complete failure upon reaching a maximum strain.
With such model, indentation experiments at increasing strain rates were
simulated on cartilage plugs and damage development was monitored over time.
Collagen damage increased with increasing strain rate from 21 to 42 %. In
contrast, damage in the non-fibrillar matrix decreased with increasing strain
rates from 72 to 34 %. Damage started to develop at a depth of approximately 20 %
of the sample height, and this was more pronounced for the slow and modest
loading rates. However, the most severe damage at the end of the compression step
occurred at the surface for the plugs subjected to 120 mm/min strain rate. In
conclusion, the present study confirms that the location and magnitude of damage
in cartilage may be strongly dependent on strain rate, even when damage occurs
solely through a strain-dependent damage mechanism.
PMID- 27514542
TI - How Valid is Placebo in the Indian Setting?
AB - BACKGROUND: The Placebo is defined as an inert substance with a potent
therapeutic effect. Its effect is attributed to its psychological and
neurobiological effect. Its use in Psychiatric drug practice, drug trials and
clinical practice is common, especially in India. Currently there is a debate
whether to use it or not as there are ethical, moral and legal issues. Also, its
mechanism of action is not known. DISCUSSION: The Indian Psychiatry scenario is
muddled in relation to use of placebo in Randomized Controlled Trials or
Psychiatric clinical practice. Despite the scepticism associated with this
phenomenon physicians get influenced by it. The present article focuses on the
reviews done so far on the efficacy and use of placebo and also the points in
favour and against the same in drug trials and psychiatric clinical practice.
SUMMARY: A number of controversies are associated with this biologically inert
substance which has no pharmacological role. Currently in medical sciences many
scientific studies have been done solely on placebo. The development in this area
may have future implications for further research.
PMID- 27514543
TI - The interaction of Wnt-11 and signalling cascades in prostate cancer.
AB - Prostate cancer (PCa) is the second most common cancer among the male population.
Conventional therapies target androgen signalling, which drives tumour growth;
however, they provide limited survival benefits for patients. It is essential,
therefore, to develop a more specific biomarker than the current gold standard,
PSA testing. The Wnt signalling pathway induces expression of target genes
through cell surface receptors. A non-canonical member of this family, Wnt-11, is
evolutionarily highly conserved and is normally expressed by various cells in the
developing embryo, as well as in the heart, liver and skeletal muscle of adult
humans. We comprehensively review several cell signalling pathways to explain how
they interact with Wnt-11, demonstrating its use as a potential biomarker for
PCa. Several studies have shown that the expression of Wnt-11 is associated with
gastric, renal and colorectal adenocarcinomas and PCa. Moreover, Wnt-11 affects
extracellular matrix composition and cytoskeletal rearrangement, and it is
required for proliferation and/or survival during cell differentiation. It was
found that PCa cell lines express high levels of Wnt-11, which allows
differentiation of the epithelial prostate tumour cells to neuron-like (NE)
cells. The NE cells produce additional factors that can cause regression after
treatment. Accumulating evidence shows that Wnt-11 could be a potential biomarker
in diagnosing PCa. Many studies have shown both non-canonical and canonical Wnts
interact with several signalling cascades such as PKC, JNK, NF-kappaB, Rho, PKA
and PI3K. In particular, evidence demonstrates Wnt-11 is involved in the
progression of PCa, thus it could have the potential to become both a specific
disease marker and an important therapeutic target.
PMID- 27514544
TI - Calcium role in human carcinogenesis: a comprehensive analysis and critical
review of literature.
AB - The central role played by calcium ion in biological systems has generated an
interest for its potential implication in human malignancies. Thus, lines of
research, on possible association of calcium metabolism regulation with
tumorigenesis, implying disruptions and/or alterations of known molecular
pathways, have been extensively researched in the recent decades. This paper is a
critical synthesis of these findings, based on a functional approach of the
calcium signaling toolkit. It provides strong support that this ubiquitous
divalent cation is involved in cancer initiation, promotion, and progression.
Different pathways have been outlined, involving equally different molecular and
cellular structures. However, if the association between calcium and cancer can
be described as constant, it is not always linear. We have identified several
influencing factors among which the most relevant are (i) the changes in local or
tissular concentrations of free calcium and (ii) the histological and
physiological types of tissue involved. Such versatility at the molecular level
may probably account for the conflicting findings reported by the epidemiological
literature on calcium dietary intake and the risk to develop certain cancers such
as the prostatic or mammary neoplasms. However, it also fuels the hypothesis that
behind each cancer, a specific calcium pathway can be evidenced. Identifying such
molecular interactions is probably a promising approach for further understanding
and treatment options for the disease.
PMID- 27514545
TI - [Protective effect of Nrf2 activation by curcumin against lead-induced toxicity
and apoptosis in SH-SY5Y cells].
AB - OBJECTIVE: To study the protective effect of nuclear factor erythroid 2-related
factor 2 (Nrf2) activation by curcumin against lead-induced toxicity and
apoptosis in SH-SY5Y human neuroblastoma cells and its impact on expression of
apoptosis-related proteins. METHODS: After the cells were treated with 0, 0.5, 1,
5, or 10 MUmol/L curcumin for 24 hours, nucleoprotein was extracted and
electrophoretic mobility shift assay was used to measure Nrf2-antioxidant
responsive element (ARE) binding capacity. The optimal concentration of curcumin
was figured out for treating cells. After pretreatment with 5 MUmol/L curcumin
for 24 hours, cells were exposed to lead acetate at different concentrations (0,
5, 25, and 125 MUmol/L for control, low-dose, medium-dose, and high-dose groups).
The 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay,
flow cytometry, and Western blot were used to evaluate cell viability, apoptosis,
and expression of apoptosis-related proteins, respectively. RESULTS: Curcumin of
5 MUmol/L caused significantly increased cell viability in low-, medium-, and
high-dose groups exposed to lead acetate for 12 hours (98.42%+/-1.12% vs 92.92%+/
0.14%, P<0.05; 95.30%+/-1.17% vs 91.15%+/-0.67%, P<0.05; 94.50%+/-1.45% vs
85.98%+/-0.45%, P<0.05). Curcumin of 5 MUmol/L also caused significantly
increased cell viability in medium-and high-dose groups exposed to lead acetate
for 24 hours (93.10%+/-1.63% vs 88.40%+/-4.13%, P<0.05; 90.13%+/-2.03% vs
83.63%+/-3.42%, P<0.05). The high-dose group had a significantly higher apoptotic
rate than the control group 6.17%+/-1.31% vs 3.30%+/-0.53%, P<0.05). Curcumin of
5.0 MUmol/L significantly reduced the apoptotic rate in the high-dose group
(2.97%+/-0.15% vs 6.17%+/-1.31%, P<0.05). Exposure to lead acetate elevated the
expression of Bax, cytochrome C, and caspase-3 and reduced Bcl-2 expression.
Curcumin of 5.0 MUmol/L significantly reduced the expression of Bax, cytochrome
C, and caspase-3 in the high-dose group (P<0.05). CONCLUSION: Nrf2 activation by
curcumin has a protective effect against lead-induced toxicity and apoptosis in
SH-SY5Y cells. The protective effect of Nrf2 against apoptosis may be associated
with the regulation of apoptosis-related proteins.
PMID- 27514546
TI - [Influence of manganese exposure via intracerebral injection on behavioristics
and substantia nigra dopaminergic neurons in rats].
AB - OBJECTIVE: To investigate the changes in behavioristics, substantia nigra
tyrosine hydroxylase (TH) immunoreactive cells, and ultrastructure of substantia
nigra neurons in rats after manganese exposure via intracerebral injection.
METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided
into exposure group and control group, with 36 rats in each group. The
stereotactic technique was used for injection of 1 MUl MnCl2.4H2O (1 mol/L) into
the corpus striatum in the exposure group, and the control group was injected
with the same volume of normal saline. The changes in rotational behavior, number
of TH immunoreactive cells in the substantia nigra, and ultrastructure of the
substantia nigra induced by apomorphine were observed at 8 hours and 1, 3, 7, 15,
and 30 days after injection, and this measure was compared with manganese
exposure via intraperitoneal injection. RESULTS: After apomorphine induction for
30 minutes, the exposure group showed a gradual increase in the number of
rotations over the time of manganese exposure (F= 176.921, P<0.01) and a
significantly higher number of rotations than the control group (F=482.654,
P<0.01). The exposure group showed a gradual reduction in the mean A value of TH
immunoreactive cells in the injured substantia nigra over the time of exposure
(F=12.009, P<0.01) , and this value differed significantly between the injured
substantia nigra in the exposure group and the contralateral substantia nigra in
the exposure group and the injured side in the control group (F=36.131, P<0.01).
At 3, 7, 15, and 30 days after exposure, the injured substantia nigra showed a
significantly lower mean A value of TH immunoreactive cells than the
contralateral side in the exposure group (all P<0.01). At 7, 15, and 30 days, the
injured substantia nigra in the exposure group showed a significantly lower mean
A value than the injured side in the control group (all P<0.01). After manganese
exposure, substantia nigra neurons showed the changes including mitochondrial
swelling, dilatation of the endoplasmic reticulum, and demyelination of nerve
fibers in different stages, which suggested the dynamic process of dopaminergic
neuron injuries. Compared with manganese exposure via intraperitoneal injection,
manganese exposure via intracerebral injection can induce behavioral changes and
injuries of the substantia nigra-striatum system more quickly. CONCLUSION:
Manganese exposure via intracerebral injection induces behavioral changes and
injuries of substantia nigra dopaminergic neurons in rats within a short time.
PMID- 27514548
TI - [Association between XRCC1 polymorphisms and chromosome damage in workers exposed
to benzene in jewelcrafting industry].
AB - OBJECTIVE: To investigate the association between the gene polymorphisms of the
DNA damage repair gene X-ray repair cross-complementing gene 1 (XRCC1) and
susceptibility to chromosome damage in workers exposed to low-concentration
benzene in the jewelcrafting industry. METHODS: A total of 286 workers exposed to
benzene in jewelcrafting enterprises were enrolled as study subjects from January
2013 to December 2014. Gas chromatography was used to measure benzene
concentration in workplace, cytokinesis-block micronucleus test was used to
analyze the level of chromosome damage in peripheral blood, and the Sequenom
technique was used to determine the single nucleotide polymorphisms of XRCC1.
RESULTS: The time-weighted average concentration of benzene in workplace was
<0.6~1.8 mg/m(3), lower than the national occupational exposure limit (6
mg/m(3)). The distribution of allele frequencies met the Hardy-Weinberg
equilibrium in genetics (P>0.05). Increase in age (RR=1.38, 95%CI 1.06~3.75) and
increase in working years (RR=1.45, 95%CI 1.18~2.58) were risk factors for the
increase in micronucleus frequency. Compared with those with the wild-type
homozygous genotype, the individuals with XRCC1 rs25487 CT genotype showed a
significantly higher risk of increase in micronucleus frequency (RR=1.51, 95% CI
1.28~3.87, P<0.05) , and the individuals with XRCC1 rs1799782 AA genotype also
showed a significantly higher risk of increase in micronucleus frequency
(RR=1.65, 95% CI 1.30~3.12, P<0.05). There was no clear association between XRCC1
rs25489 polymorphisms and micronucleus frequency (P>0.05). CONCLUSION: Exposure
to low-concentration benzene may cause chromosome damage in workers exposed to
benzene, and the XRCC1 polymorphisms rs 25487 and rs1799782 may be associated
with chromosome damage induced by benzene.
PMID- 27514547
TI - [Association between hypertension and serum microRNA21 and microRNA133a in ocean
seamen].
AB - OBJECTIVE: To investigate the prevalence of hypertension in ocean seamen and
major influencing factors, as well as the association between hypertension and
serum microRNA21 and microRNA133a. METHODS: Health examination and a
questionnaire survey were performed for 780 ocean seamen who underwent physical
examination in an international travel healthcare center in Fujian, China from
January to June, 2014. TaqMan RT-qPCR was used to measure the serum levels of
microRNA21 and microRNA133a in seamen with hypertension. RESULTS: The prevalence
of hypertension differed significantly between the ocean seamen with different
ages, education levels, marital status, body mass index (BMI) values, drinking
frequencies, and numbers of sailing years (P<0.05). The prevalence rate of
hypertension in the ocean seamen increased with the increasing drinking frequency
(chi(2)=9.02, P<0.05) , decreased with the increase in degree of education
(chi(2)=11.578, P<0.05) , and increased with the increase in the number of
sailing years (chi(2)=28.06, P<0.05). The hypertensive ocean seamen had
significantly higher expression levels of microRNA21 and MicroRNA133a than the
healthy ocean seamen (microRNA21: 7.87+/-5.46 vs 1.03+/-0.80, P<0.05;
MicroRNA133a: 7.45+/-1.94 vs 4.52+/-1.15, P<0.05). The multivariate analysis
showed that a high level of microRNA21 (OR=1.61, 95% CI: 1.22~2.11) , a high
level of microRNA133a (OR=1.52, 95% CI: 1.24~1.87) , drinking (OR=1.64, 95% CI:
1.08~2.50) , overweight based on BMI (OR=1.18, 95%CI: 1.07~1.30) , and many
sailing years (OR=2.89, 95% CI: 1.14~7.30) were risk factors for hypertension.
CONCLUSION: The prevention and treatment of hypertension in ocean seamen should
be enhanced. Excessive drinking should be controlled, and sailing time should be
arranged reasonably. The microRNA21 and microRNA133a may be associated with the
development and progression of hypertension in ocean seamen.
PMID- 27514549
TI - [Toxic effect of trichloroethylene on liver cells with CYP3A4 gene defect].
AB - OBJECTIVE: To investigate the toxic effect of trichloroethylene on liver cells
with CYP3A4 gene defect. METHODS: The normal human liver cells (L02 cells) and
liver cells with CYP3A4 gene defect were exposed to trichloroethylene at
different doses (0.0, 0.4, 0.8, 1.6, 3.2, and 6.4 mmol/L). CCK8 assay and RT-qPCR
were used to measure cell viability and changes in the expression of apoptosis
genes and oncogenes. RESULTS: After being exposed to trichloroethylene at doses
of 1.6, 3.2, and 6.4 mmol/L, the liver cells with CYP3A4 gene defect showed
significantly higher cell viability than L02 cells (0.91+/-0.06/0.89+/
0.05/0.85+/-0.07 vs 0.80+/-0.04/0.73+/-0.06/0.67+/-0.07, P<0.05). The L02 cells
in the 0.8~3.2 mmol/L trichloroethylene groups showed significant increases in
the expression of the apoptosis genes caspase-3, caspase-8, and caspase-9
(P<0.05) , as well as the oncogenes c-myc, c-fos, and k-ras (P<0.05). Compared
with the L02 cells, the cells with CYP3A4 gene defect showed significant
reductions in the expression of the apoptosis genes caspase-3, caspase-8, and
caspase-9 and the oncogenes c-myc, c-fos, and k-ras (P<0.05). CONCLUSION:
Trichloroethylene exposure has a less effect on the expression of apoptosis genes
and oncogenes in liver cells with CYP3A4 gene defect than in normal human liver
cells, suggesting that CYP3A4 gene defect reduces the inductive effect of
trichloroethylene on apoptosis genes and oncogenes.
PMID- 27514550
TI - [Influence of two positions for measuring instrument adapter on measurement of
hand-transmitted vibration in grinding machine].
AB - OBJECTIVE: To investigate the influence of two positions for measuring instrument
adapter on the measurement of hand-transmitted vibration in grinding machine
using the intraclass correlation coefficient (ICC) of reliability assessment
index, and to provide a basis for studies on the measurement standard for hand
transmitted vibration. METHODS: With reference to the measurement standard for
hand-transmitted vibration ISO 5349 Mechanical vibration-Measurement and
evaluation of human exposure to hand-transmitted vibration-Part 1: General
requirements and Mechanical vibration-Measurement and evaluation of human
exposure to hand-transmitted vibration-Part 2: Practical guidance for measurement
at the workplace, the domestic AWA5936 hand-transmitted vibration measuring
instrument and SVAN-106 hand-transmitted vibration measuring instrument from
Poland were used to measure hand-transmitted vibration in 3 workers for grinding
machine in a foundry for 5 days continuously from September to October, 2014, and
Y-axis data were recorded and compared. RESULTS: In worker A, the "T" -shaped
adapter had a significantly higher mean Y-axis accelerated speed effective value
than the "O" -shaped adapter [4.34 m/s(2) (95%CI 4.05(-)4.63) vs 2.32 m/s(2)
(95%CI 2.27~2.38) , t=13.781, P<0.01]. In workers B and C, AWA5936 "U" -shaped
adapter (placed at the position of the handle of grinding machine) had lower
degrees of data variation of 12.55% and 15.77%, respectively, suggesting good
data stability. The measurement results showed significant differences across
different positions of adapter (P<0.01) and between all adapters except "O"
shaped and line-shaped adapters (all P<0.01) , while the measurement results
showed no significant differences between the "O" -shaped and line-shaped
adapters (P>0.01). The comparison of the measurement results of AWA5936 vibration
measuring instrument with an "U" -shaped adapter and SVAN-106 vibration measuring
instrument with an "S" -shaped adapter showed an ICC of >0.80 (ICC=0.82) , while
the comparison of the measurement results of AWA5936 vibration measuring
instrument with an "O" -shaped adapter and SVAN-106 vibration measuring
instrument showed an ICC of <0.40. CONCLUSION: SVAN-106 vibration measuring
instrument with an "S" -shaped adapter placed at the palm and AWA5936 vibration
measuring instrument with an "U" -shaped adapter placed at the handle of grinding
machine can give comparable measurement results with good reliability.
PMID- 27514551
TI - [A survey of mental health status in armored vehicle crew].
AB - OBJECTIVE: To investigate the mental health status in armored vehicle crew
(commanders, gunners, and drivers) , to know the level of mental health in them,
and to provide educational intervention. METHODS: In April 2009, 120 male armored
vehicle crew with >2 driving years were enrolled as battle group, and 70 male
persons within the same age group who were not engaged in armored vehicle
operation were enrolled as control group. The Symptom Checklist-90 (SCL-90) was
used to evaluate the mental status of the 180 subjects. RESULTS: Compared with
the control group, the battle group showed significantly higher scores on the
subscales of obsessive-compulsive symptom, interpersonal sensitivity, depression,
anxiety, phobic anxiety, and paranoid ideation (t=2.323, 3.250, 3.158, 2.712,
2.391, and 2.137, all P<0.05) , as well as significantly higher total score,
number of positive items, and average score of positive symptoms (t=4.128, 4.357,
and 4.632, all P<0.05). In the battle group, the scores on the subscales of
somatization, obsessive-compulsive symptom, interpersonal sensitivity,
depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism,
and additional items, total score, number of positive items, and average score of
positive symptoms were significantly lower than the military reference values
(t=4.364, 5.127, 5.280, 3.783, 7.012, 5.361, 4.369, 6.167, 6.476, 3.558, 6.357,
4.379, and 6.763, all P<0.05). CONCLUSION: A survey should be performed on the
mental health status of armored vehicle crew, including obsessive-compulsive
symptom, interpersonal sensitivity, depression, and anxiety. Mental health
service for the crew should be enhanced to improve their psychological quality.
PMID- 27514552
TI - [Research on the work-related disease and its influencing factors of midwives in
Fujian Province].
PMID- 27514553
TI - [Investigation on occupational health status of workers in Xinjiang coal-fired
power plant].
PMID- 27514554
TI - [Intervention of systolic pressure and left ventricular hypertrophy in rats under
cold stress].
AB - OBJECTIVE: To investigate the effects of different drugs on systolic blood
pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously
hypertensive rats under cold stress. METHODS: A total of 40 male spontaneously
hypertensive rats aged 10 weeks (160~200 g) were given adaptive feeding for 7
days at a temperature of 20+/-1 degrees C and then randomly divided into control
group, cold stress group, metoprolol group, amlodipine group, and benazepril
group, with 8 rats in each group. SBP, body weight, and heart rate were measured
once a week. After the rats were sacrificed by exsanguination, left ventricular
weight (LVW) was measured, and left ventricular weight index (LVWI; mg/g) was
calculated. Radioimmunoassay was used to measure the concentrations of endothelin
1 (ET-1) and angiotensin-II (Ang-II) in plasma and myocardium, and the chemical
method was used to measure the concentrations of nitric oxide (NO) in plasma and
myocardium. RT-PCR was used to measure the mRNA expression of endothelin-A
receptor. RESULTS: Compared with the cold stress group, all medication groups
showed significant reductions in SBP since week 5 (P<0.05). The cold stress group
showed a significant increase in LVWI compared with the control group (3.38+/
0.27 mg/g vs 2.89+/-0.19 mg/g, P<0.05). The amlodipine group showed a significant
reduction in LVWI compared with the cold stress group (2.98+/-0.28 mg/g vs 3.38+/
0.27 mg/g, P<0.05). The cold stress group showed a significant reduction in
plasma NO concentration compared with the control group (104.9+/-19.5 MUmol/L vs
129.3+/-17.8 MUmol/L, P<0.05) ; compared with the cold stress group, all the
medication groups showed significant increases in blood NO concentration
(P<0.05). The cold stress group showed a significant increase in myocardial ET-1
concentration compared with the control group (6.3+/-1.5 pg/100 mg vs 4.5+/-1.9
pg/100 mg, P<0.05) ; compared with the cold stress group, the amlodipine group
showed a significant reduction in myocardial ET-1 concentration (4.4+/-1.0 pg/100
mg vs 6.3+/-1.5 pg/100 mg, P<0.05). The cold stress group had significantly
higher mRNA expression of endothelin-A receptor than the control group (0.86+/
0.23 vs 0.45+/-0.16, P<0.01) ; compared with the cold stress group, the
amlodipine group showed a significant reduction in the mRNA expression of
endothelin-A receptor (0.41+/-0.14 vs 0.86+/-0.23, P<0.01). CONCLUSION:
Amlodipine can reduce the increase in SBP and inhibit LVH in spontaneously
hypertensive rats under cold stress.
PMID- 27514555
TI - [Effects of expression of calpain mRNA in rabbits exposed to vibration by hind
legs].
AB - OBJECTIVE: To study the effects of expression of calpain mRNA in rabbits exposed
to vibration by hind legs. METHODS: 32 New Zealand rabbits were randomly divided
into a control group and 3 experimental groups according to 4-hour energy
equivalent frequency-weighted acceleration[ahw (4)]: low (4.33 m/s(2)) , moderate
(8.67 m/s(2)) and high (17.34 m/s(2)) intensity group to accepted the vibration
by hind legs. 45 ds later, brain and skeletal muscle tissue of rabbits were taken
to detect the expression of calpain-1 and calpain-2 mRNA by RT-qPCR technique.
RESULTS: The relative content of calpain-1 mRNA in the brain tissues in rabbits
of low, medium and high intensity group were 8.35+/-3.75,9.64+/-4.54,5.10+/-5.26.
While the relative content of calpain-2 mRNA in the brain tissues in rabbits of
low, medium and high intensity group were 7.34+/-4.97,8.50+/-5.66, 8.16+/-5.59.
Compared with the control group (1.10+/-0.29, 0.56+/-0.43) , the expression of
calpain-1 and calpain-2 mRNA of the intensity groups showed an significantly
increasing trend (P<0.01). In skeletal muscle tissue, the relative content of
calpain-1 mRNA were 4.36+/-2.05, 7.37+/-4.06, 12.46+/-6.21.Compared with the
control group (0.98+/-0.59) , the expression of calpain-1 mRNA of experiment
groups were significantly higher (P<0.05) .The expression of calpain-2 mRNA of
the intensity groups had no significantly difference with the control group
(P>0.05). CONCLUSION: The expression of calpain-1 and calpain-2 mRNA can be
promoted by the vibration by the hind legs.
PMID- 27514556
TI - [Influence of puerarin on proliferative activity of human fetal scleral
fibroblasts and expression of collagen type I and matrix metalloproteinase-2 in
power frequency electromagnetic field].
AB - OBJECTIVE: To investigate the influence of puerarin on the proliferative activity
of human fetal scleral fibroblasts (HFSFs) and the expression of collagen type I
and matrix metalloproteinase-2 (MMP-2) in HFSFs in the power frequency
electromagnetic field. METHODS: HFSFs were cultured and divided into four
radiation groups (0.2 mT, 50 Hz) and control group. Puerarin at concentrations of
0.0, 1.0, 5.0, and 10.0 MUmol/L was added to the four radiation groups,
respectively. The methyl thiazolyl tetrazolium colorimetry was used to measure
the influence on the proliferative activity of HFSFs, Western blot and RT-qPCR
were used to measure the protein and mRNA expression of collagen type I and MMP-2
induced by puerarin in the power frequency electromagnetic field. RESULTS: The
radiation groups and control group showed significant increases in the
proliferative activity of HFSFs over the culture time (F= 959.472 and 279.468,
both P<0.01). At 24 and 48 hours, the radiation groups showed significantly lower
proliferative activity than the control group (0.432+/-0.038/0.591+/-0.017 vs
0.536+/-0.034/0.801+/-0.020, both P<0.01). With the increasing concentration of
puerarin (0.0, 1.0, 5.0, and 10.0 MUmol/L) , the proliferative activity of HFSFs
significantly increased, with A values of 0.598+/-0.031, 0.809+/-0.041, 0.910+/
0.037, and 0.983+/-0.054, respectively (P<0.05). After exposure for 24 hours, the
radiation groups showed significantly lower protein expression of collagen type I
and significantly higher protein expression of MMP-2 (t=7.917 and 7.831, both
P<0.01) ; compared with the 0.0 MUmol/L puerarin group, the 1.0, 5.0, and 10.0
MUmol/L puerarin groups showed significant increases in the protein expression of
collagen type I and significant reductions in the protein expression of MMP-2
(all P<0.01). Compared with the control group, the radiation groups showed
significant reductions in the mRNA expression of collagen type I and MMP-2
(t=17.293 and 16.378, both P<0.01) ; compared with the 0.0 MUmol/L puerarin
group, the 1.0, 5.0, and 10.0 MUmol/L puerarin groups showed significant
increases in the mRNA expression of collagen type I and significant reductions in
the mRNA expression of MMP-2 (P<0.01). CONCLUSION: Puerarin can inhibit the
reduction in the proliferative activity of HFSFs in the power frequency
electromagnetic field, upregulate the expression of collagen type I, downregulate
the expression of MMP-2, and thus exert its protective effect.
PMID- 27514557
TI - [Application of standardization of medical care model for chronic mild lead
poisoning].
AB - OBJECTIVE: To standardize the treatment and evaluate the clinical application
effectiveness of clinical pathway (CP) in chronic mild lead poisoning. METHODS:
60 patients with chronic mild lead poisoning hospitalized from Jan. 2014 to
Dec.2014 were enrolled for the study group, 60 patients with chronic mild lead
poisoning hospitalized from Jan.2013 to Dec.2013 were enrolled for the control
group. The study group were cared according to clinical pathway, the control
group received routine therapy; the clinical application effectiveness were
compared between the two groups. RESULTS: No adverse drug reactions occurred in
both groups. The curative ratio was significantly higher in the study group than
in the control group (96.7% vs 86.0%, P<0.05) , the rate of patients'
satisfaction to medical care significantly higher in the study group (98.3% vs
88.3%, P<0.05) , the rate of health education awareness higher in the study group
(95.0% vs 81.7%, P<0.05) , the course of treatment shorter in the study group
(3.2+/-0.6 vs 3.4+/-0.7, P<0.05) , the medical cost less in the study group
(5773.5 yuan+/-1242.1 yuan vs 6354.7 yuan+/-1177.0 yuan, P<0.05) , the length of
hospitalization was shorter in the study group (21.9 d+/-6.7 d vs 24.6 d+/-7.9 d,
P<0.05). The variation rate of clinical pathway was 13.3% in clinical pathway
group. CONCLUSION: The implementation of clinical pathway could improve the
curative ratio, satisfaction, and health education awareness. The course of
treatment, length of hospital stay and costs of hospitalization in the study
group could be obviously shorter and less, and there is a little variation rate
in the clinical pathway.
PMID- 27514558
TI - [Clinical analysis of chronic lead poisoning and liver function damage].
PMID- 27514559
TI - [Early reduction of frostbite for depth of management of occupational acute
finger].
PMID- 27514560
TI - [A case of chronic myeloid leukemia caused by benzene].
PMID- 27514563
TI - [Evaluation of uncertainty for determination of manganese dioxide in air of
workplace by flame atomic absorption spectrometry].
PMID- 27514561
TI - [Determination of HVA and VMA in urine using high performance liquid
chromatography-tandem mass spectrometry].
AB - OBJECTIVE: To establish a method for the determination of homovanillic acid (HVA)
and vanil mandelic acid (VMA) in urine, using high performance liquid
chromatography-tandem mass spectrometry (HPLC/MS/MS) detection. METHODS: A 200
MUl volume of urine sample added with 20 MUl chlorzoxazone internal standard was
mixed in a centrifuge tube, then added 100MUL methanol (containing 1% acetic
acid) , vortex mixed and centrifuged at 13 000 rpm for 1 min. A 10 MUl volume of
the above supernatant solution was injected into HPLC/MS/MS system for
quantitative analysis. RESULTS: With internal standard method, the calibration
curves of HVA and VMA were linear in the range of 20~10 000 ng/ml and 20~7 500
ng/ml, with correlation coefficient of 0.995 6 and 0.997 0, respectively. The LOQ
of HVA and VMA was 4.69 ng/ml and 2.33 ng/ml, respectively. The method recoveries
were in the range of 85.72%~117.95% for HVA, and 95.82%~113.78% for VMA.
CONCLUSION: This method is simple, rapid and characterized with acceptable
sensitivity and accuracy to meet the requirements for the analysis of
homovanillic acid and vanilla mandelic acid.
PMID- 27514562
TI - [Determination of trace gallium by graphite furnace atomic absorption
spectrometry in urine].
AB - OBJECTIVE: To establish a method for determination trace gallium in urine by
graphite furnace atomic absorption spectrometry (GFAAS). METHODS: The ammonium
dihydrogen phosphate was matrix modifier. The temperature effect about pyrolysis
(Tpyr) and atomization temperature were optimized for determination of trace
gallium. The method of technical standard about within-run, between-run and
recoveries of standard were optimized. RESULTS: The method showed a linear
relationship within the range of 0.20~80.00 MUg/L (r=0.998). The within-run and
between-run relative standard deviations (RSD) of repetitive measurement at 5.0,
10.0, 20.0 MUg/L concentration levels were 2.1%~5.5% and 2.3%~3.0%. The detection
limit was 0.06 MUg/L. The recoveries of gallium were 98.2%~101.1%. CONCLUSION:
This method is simple, low detection limit, accurate, reliable and reproducible.
It has been applied for determination of trace gallium in urine samples those who
need occupation health examination or poisoning diagnosis.
PMID- 27514564
TI - [Risk assessment on occupational exposure to sulfuric acid and sodiumhydroxide in
workplace].
PMID- 27514565
TI - [Standardization of medical report for occupational physical examination in Gansu
Province].
PMID- 27514566
TI - [Problems and countermeasures in the implementation of Technical Specifications
for Occupational Health Surveillance on noise-exposed workers].
PMID- 27514567
TI - [The principle and application of TCR gene mutation test].
PMID- 27514569
TI - Hybrid Copper-Silver Conductive Tracks for Enhanced Oxidation Resistance under
Flash Light Sintering.
AB - We developed a simple method to prepare hybrid copper-silver conductive tracks
under flash light sintering. The developed metal nanoparticle-based ink is
convenient because its preparation process is free of any tedious washing steps.
The inks were composed of commercially available copper nanoparticles which were
mixed with formic acid, silver nitrate, and diethylene glycol. The role of formic
acid is to remove the native copper oxide layer on the surface of the copper
nanoparticles. In this way, it facilitates the formation of a silver outer shell
on the surface of the copper nanoparticles through a galvanic replacement. In the
presence of formic acid, the copper nanoparticles formed copper formate, which
was present in the unsintered tracks. However, under illumination by a xenon
flash light, the copper formate was then converted to copper. Moreover, the
resistance of the copper-only films increased by 6 orders of magnitude when
oxidized at high temperatures (~220 degrees C). However, addition of silver
nitrate to the inks suppressed the oxidation of the hybrid copper-silver films,
and the resistance changes in these inks at high temperatures were greatly
reduced. In addition, the hybrid inks proved to be advantageous for use in
electrical circuits as they demonstrated a stable electrical conductivity after
exposure to ambient air at 180 degrees C.
PMID- 27514568
TI - Reliability and validity of the patient disability-oriented diagnostic
nomenclature system for prosthetic dentistry.
AB - PURPOSE: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic
nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and
improve prosthodontic treatment. This system specifies patient disability and the
causative factor (i.e. "B (disability) caused by A (causative factor)"). The
purpose of this study was to examine the reliability and validity of this DNS.
STUDY SELECTION: The JPS Clinical Guideline Committee assessed mock patient
charts and formulated disease names using the new DNS. Fifty validators,
comprising prosthodontic specialists and dental residents, made diagnoses using
the same patient charts. Reliability was evaluated as the consistency of the
disease names among the validators, and validity was evaluated using the
concordance rate of the disease names with the reference disease names. RESULTS:
Krippendorff's alpha was 0.378 among all validators, 0.370 among prosthodontic
specialists, and 0.401 among dental hospital residents. Krippendorff's alpha for
10 validators (3 specialists and 7 residents) with higher concordance rates was
0.524. Two validators (1 specialist and 1 resident) with the highest concordance
rates had a Krippendorff's alpha of 0.648. Common disease names had higher
concordance rates, while uncommon disease names showed lower concordance rates.
These rates did not show correlation with clinical experience of the validator or
time taken to devise the disease name. CONCLUSIONS: High reliability was not
found among all validators; however, validators with higher concordance rates
showed better reliability. Furthermore, common disease names had higher
concordance rates. These findings indicate that the new DNS for prosthodontic
dentistry exhibits clinically acceptable reliability and validity.
PMID- 27514570
TI - Diffusion kurtosis imaging study on temporal lobe after nasopharyngeal carcinoma
radiotherapy.
AB - PURPOSE: Diffusion kurtosis imaging (DKI) is a MRI technique which can measure
alterations in the diffusion of water molecules to reflect tissue changes in both
white and grey matter. This study evaluated the potential of DKI for the early
diagnosis of radiation-induced temporal lobe changes in the grey and white matter
of the temporal lobe in patients with nasopharyngeal carcinoma (NPC). MATERIALS
AND METHODS: Sixty patients with NPC who had normal MRI brain scans were enrolled
and underwent DKI at 1 week (n=20), 6 months (n=20) or 1 year (n=20) after
radiotherapy; 20 normal control individuals were also evaluated. Nonlinear
fitting routines and equations were used to calculate mean diffusion (MD) and
mean kurtosis (MK) and fractional anisotropy (FA). Analysis of variance was used
to compare the MK/MD/FA values of white and grey matter between groups. RESULTS:
Compared to the normal control group, grey and white matter MK values were
significantly higher at 1 week after radiotherapy and significantly lower at 6
months and 1 year after radiotherapy in patients with NPC, whereas the grey and
white matter MD values were significantly lower at 1 week after radiotherapy and
returned to normal by 6 months and 1 year after radiotherapy. CONCLUSION: DKI can
be used to detect radiotherapy-induced changes in both the white and grey matter
of temporal lobe in patients with NPC. MK and MD values may represent reliable
indicators for the early diagnosis of radiation-induced temporal lobe changes in
NPC.
PMID- 27514571
TI - Eppur Si Muove: The dynamic nature of physiological control of renal blood flow
by the renal sympathetic nerves.
AB - Tubuloglomerular feedback and the myogenic response are widely appreciated as
important regulators of renal blood flow, but the role of the sympathetic nervous
system in physiological renal blood flow control remains controversial. Where
classic studies using static measures of renal blood flow failed, dynamic
approaches have succeeded in demonstrating sympathetic control of renal blood
flow under normal physiological conditions. This review focuses on transfer
function analysis of renal pressure-flow, which leverages the physical
relationship between blood pressure and flow to assess the underlying vascular
control mechanisms. Studies using this approach indicate that the renal nerves
are important in the rapid regulation of the renal vasculature. Animals with
intact renal innervation show a sympathetic signature in the frequency range
associated with sympathetic vasomotion that is eliminated by renal denervation.
In conscious rabbits, this sympathetic signature exerts vasoconstrictive,
baroreflex control of renal vascular conductance, matching well with the
rhythmic, baroreflex-influenced control of renal sympathetic nerve activity and
complementing findings from other studies employing dynamic approaches to study
renal sympathetic vascular control. In this light, classic studies reporting that
nerve stimulation and renal denervation do not affect static measures of renal
blood flow provide evidence for the strength of renal autoregulation rather than
evidence against physiological renal sympathetic control of renal blood flow.
Thus, alongside tubuloglomerular feedback and the myogenic response, renal
sympathetic outflow should be considered an important physiological regulator of
renal blood flow. Clinically, renal sympathetic vasomotion may be important for
solving the problems facing the field of therapeutic renal denervation.
PMID- 27514572
TI - Association of testosterone and BDNF serum levels with craving during alcohol
withdrawal.
AB - Preclinical and clinical studies show associations between testosterone and brain
derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone
have been independently reported to influence alcohol consumption. Therefore, we
aimed to investigate a possible interplay of testosterone and BDNF contributing
to alcohol dependence. Regarding possible interplay of testosterone and BDNF and
the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum
levels in our research. We investigated testosterone and BDNF serum levels in a
sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7,
and 14) and compared them to a healthy male control group (n = 17). The
testosterone serum levels were significantly (p < 0.001) higher in the patients'
group than in the control group and decreased significantly during alcohol
withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol
withdrawal (days 1-7) was significantly associated with the BDNF serum levels
(day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels
(putatively mirroring high HPA activity), we found a significant association of
BDNF and testosterone as well as with alcohol craving measured by the Obsessive
and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of
BDNF and testosterone serum levels, which may be relevant for the symptomatology
of alcohol dependence. Further studies are needed to clarify our results.
PMID- 27514573
TI - Effect of electrolytic lesions of the dorsal diencephalic conduction system on
the distribution of Fos-like immunoreactivity induced by rewarding electrical
stimulation.
AB - The dorsal diencephalic conduction system (DDC) is an important pathway of the
brain reward circuitry, linking together forebrain and midbrain structures. The
present work was aimed at describing the effect of a DDC lesion on the
distribution of Fos-like immunoreactivity (FLIR) following intracranial self
stimulation (ICSS) of the lateral hypothalamus (LH). Rats were implanted with
monopolar electrodes and divided into three groups; the first two groups were
trained to self-stimulate at the LH, whereas the third group received no
stimulation and served as a control. Among the two groups that were trained for
ICSS, one of them received a lesion at the DDC and was tested for ICSS on the
subsequent 5days. On the last day of testing, control rats were placed in operant
chambers without receiving any stimulation, and the remaining rats were allowed
to receive the stimulation for 1h. All rats were then processed for FLIR. As
previously shown, a lesion at the DDC resulted in significant attenuations of the
rewarding effectiveness of LH stimulation. Results also show a higher FLIR in
several reward-related areas following LH stimulation, especially in the
hemisphere ipsilateral to the stimulation electrode. Compared to non-lesioned
rats, lesioned animals had lower FLIR in certain brain regions, suggesting that
those regions that were activated by the rewarding stimulation may be
functionally interconnected with the DDC.
PMID- 27514574
TI - Mitochondrial changes and oxidative stress in a mouse model of Zellweger syndrome
neuropathogenesis.
AB - Zellweger syndrome (ZS) is a peroxisome biogenesis disorder that involves
significant neuropathology, the molecular basis of which is still poorly
understood. Using a mouse model of ZS with brain-restricted deficiency of the
peroxisome biogenesis protein PEX13, we demonstrated an expanded and
morphologically modified brain mitochondrial population. Cultured fibroblasts
from PEX13-deficient mouse embryo displayed similar changes, as well as increased
levels of mitochondrial superoxide and membrane depolarization; this phenotype
was rescued by antioxidant treatment. Significant oxidative damage to neurons in
brain was indicated by products of lipid and DNA oxidation. Similar overall
changes were observed for glial cells. In toto, these findings suggest that
mitochondrial oxidative stress and aberrant mitochondrial dynamics are associated
with the neuropathology arising from PEX13 deficiency.
PMID- 27514575
TI - Subthalamic deep brain stimulation and dopaminergic medication in Parkinson's
disease: Impact on inter-limb coupling.
AB - Patients with Parkinson's disease (PD) often present with bimanual coordination
deficits whose exact origins remain unclear. One aspect of bimanual coordination
is inter-limb coupling. This is characterized by the harmonization of movement
parameters between limbs. We assessed different aspects of bimanual coordination
in patients with PD, including inter-limb coupling, and determined whether they
are altered by subthalamic (STN) deep brain stimulation (DBS) or dopaminergic
medication. Twenty PD patients were tested before STN DBS surgery; with and
without medication. Post- surgery, patients were tested with their stimulators on
and off as well as with and without medication. Patients were asked to perform a
unimanual and bimanual rapid repetitive diadochokinesis task. The difference in
mean amplitude and mean duration of cycles between hands was computed in order to
assess inter-limb coupling. Also, mean angular velocity of both hands and
structural coupling were computed for the bimanual task. There was a positive
effect of medication and stimulation on mean angular velocity, which relates to
clinical improvement. PD patients exhibited temporal inter-limb coupling that was
not altered by either medication or STN stimulation. However, PD patients did not
exhibit spatial inter-limb coupling. Again, this was not altered by medication or
stimulation. Collectively, the results suggest that structures independent of the
dopaminergic system and basal ganglia may mediate temporal and spatial inter-limb
coupling.
PMID- 27514576
TI - Optimisation of image reconstruction for phase-contrast x-ray Talbot-Lau imaging
with regard to mechanical robustness.
AB - X-ray grating-based phase-contrast imaging opens new opportunities, inter alia,
in medical imaging and non-destructive testing. Because, information about the
attenuation properties and about the refractive properties of an object are
gained simultaneously. Talbot-Lau imaging requires the knowledge of a reference
or free-field image. The long-term stability of a Talbot-Lau interferometer is
related to the time span of the validity of a measured reference image. It would
be desirable to keep the validity of the reference image for a day or longer to
improve feasibility of Talbot-Lau imaging. However, for example thermal and other
long-term external influences result in drifting effects of the phase images.
Therefore, phases are shifting over time and the reference image is not valid for
long-term measurements. Thus, artifacts occur in differential phase-contrast
images. We developed an algorithm to determine the differential phase-contrast
image with the help of just one calibration image, which is valid for a long time
period. With the help of this algorithm, called phase-plane-fit method, it is
possible to save measurement-time, as it is not necessary to take a reference
image for each measurement. Additionally, transferring the interferometer
technique from laboratory setups to conventional imaging systems the necessary
rigidity of the system is difficult to achieve. Therefore, short-term effects
like vibrations or distortions of the system lead to imperfections within the
phase-stepping procedure. Consequently, artifacts occur in all three image
modalities (differential phase-contrast image, attenuation image and dark-field
image) of Talbot-Lau imaging. This is a problem with regard to the intended use
of phase-contrast imaging for example in clinical routine or non-destructive
testing. In this publication an algorithm of Vargas et al is applied and
complemented to correct inaccurate phase-step positions with the help of a
principal component analysis (PCA). Thus, it is possible to calculate the
artifact free images. Subsequently, the whole algorithm is called PCA
minimization algorithm.
PMID- 27514577
TI - Sequences and expression of pathway-specific complement components in developing
red-tailed phascogale (Phascogale calura).
AB - Marsupials are born immunologically premature, relying on cells and molecules in
maternal milk for immune protection. Both immunoglobulin and complement proteins
have been identified in marsupial milk, but the expression of specific complement
proteins remains largely unexplored. We report partial cDNA sequences for two
complement-activating proteins, C3, C1r, CFP and MASP2, in liver tissues from red
tailed phascogale (Phascogale calura). Conservation of functionally relevant
motifs were identified in the translated cDNA sequences from phascogale C3, CFP
and MASP2 and their eutherian homologues. Gene expression of representative
molecules from each of the major complement pathways was also investigated in
whole body tissues from 1 to 18 day old animals and liver tissues from 31-day to
14-month old animals. Average complement expression in whole bodies and liver
tissues of C1r, CFP, MASP2 and C3 increased significantly in juveniles compared
to pouch young, presumably due to the maturation of the young's own complement
system. Comparing expression in liver tissues only, we found that the average CFP
expression were higher in pouch young compared to juveniles, while results were
still statistically similar to the average expression of all tissues for C1r,
MASP2 and C3. The average complement expression then significantly decreased as
the animals aged into adulthood.
PMID- 27514578
TI - Dementia after Three Months and One Year from Stroke: New Onset or Previous
Cognitive Impairment?
AB - OBJECTIVE: Stroke is an important risk factor for dementia, but the exact
mechanism involved in cognitive decline remains unclear. METHODS: Patients were
divided into 2 groups: poststroke dementia group (PSD) and poststroke nondementia
group (PSND). Variables and neuroradiological hallmarks were compared between 2
groups at 3 months (114 subjects) and 1 year (105 subjects) after stroke.
RESULTS: Older age (OR 1.11, 95% CI 1.0-1.2; P < .05), education (OR .6, 95% CI
.4-.8; P < .05), prestroke IQCODE (Informant Questionnaire on Cognitive Decline
in the Elderly; OR .78, 95% CI .1-5.9; P < .05), premorbid apathy (OR 2.03, 95%
CI 1.1-3.7; P < .05), and medial temporal lobe atrophy (MTLA) (OR 6.14, 95% CI
1.4-26.2; P < .05) were independently associated with PSD at 3 months after a
cerebrovascular event, whereas at 1-year follow-up older age (OR 1.1, 95% CI 1.0
1.2; P < .05), prestroke IQCODE (OR .05, 95% CI .0-.9; P < .05), MTLA (OR 1.3,
95% CI 1.0-1.6; P < .05), and APACHE II (Acute Physiology and Chronic Health
Evaluation; OR .6, 95% CI .4-.9; P < .05) were independently associated with PSD.
CONCLUSIONS: Acute cerebrovascular disease could not be the only one mechanism
explaining PSD. Neurodegenerative pathology must be taken into account.
PMID- 27514579
TI - Comparison of Baseline Heart Rate Variability in Stable Ischemic Heart Disease
Patients with and without Stroke in Long-Term Observation.
AB - GOAL: Decreased heart rate variability (HRV) has predictive value in
postinfarction as well as in ischemic stroke patients. However, it is unknown if
ischemic heart disease (IHD) patients who are at high risk of stroke have
different HRV profile. The goal of this study was to compare baseline HRV
(traditional and novel indices) in stable IHD patients with and without stroke in
long-term observation. METHODS: A total of 139 consecutive patients with stable
IHD scheduled for coronary angiography were enrolled. Five-minute
electrocardiogram readings were taken. Traditional and novel HRV measures were
calculated. After 70.06 +/- 4.297 months of follow-up, baseline HRV indices in
patients who had had a stroke were compared with indices in patients without the
aforementioned cerebrovascular event. RESULTS: During follow-up, 6 patients
developed stroke. Compared to patients without such a cerebrovascular event,
these patients with stroke had lower values for the following HRV indices: de
Hann long-term irregularity (30,521 +/- 32,767 versus 46,678 +/- 25,328; P <
.05), Yeh interval index (.0207 +/- .0208 versus .0326 +/- .0157; P < .05), Organ
BAND (3.0563 +/- 3.328 versus 4.515 +/- 2.276; P < .05), Dalton standard
deviation (SD) (17,887 +/- 17,636 versus 29,859 +/- 16,478; P < .05), Zugaib
short-term variability (.004 +/- .00416 versus .00622 +/- .00418; P < .05),
Zugaib long-term variability (.0161 +/- .0151 versus .0247 +/- .0115; P < .05),
standard deviation of all NN intervals (8,954 +/- 8,812 versus 16,724 +/- 11,594;
P < .05), total power (2,616 +/- 4,855 versus 4,678 +/- 4,653; P < .05), w2 (.71
+/- .338 versus 1.719 +/- 1.08; P < .05), w3 (1.399 +/- .924 versus 2.552 +/-
1.609; P < .05), and w4 (1.367 +/- 1.705 versus 2.824 +/- 2.027; P < .05). No
significant differences in other analyzed indices were observed. CONCLUSIONS:
Patients with IHD and stroke in long-term observation have different baseline
profiles of HRV indices. Further investigations are needed to assess the
usefulness of HRV analysis in stroke risk assessment.
PMID- 27514580
TI - Stroke Laterality Bias in the Management of Acute Ischemic Stroke.
AB - BACKGROUND: Little is known of the impact of stroke laterality on the management
process and outcome of patients with acute ischemic stroke (AIS). METHODS:
Consecutive patients admitted to a general hospital over 1 year with
supratentorial AIS were eligible for inclusion in the study. Baseline
characteristics and risk factors, delays in hospital admission, imaging,
intrahospital transfer to an acute stoke unit, stroke severity and
classification, length of hospital admission, as well as 10-year mortality were
measured and compared among right and left hemisphere AIS patients. RESULTS:
There were 141 patients (77 men, 64 women; median age 73 [interquartile range 63
79] years), There were 71 patients with left hemisphere AIS and 70 with right
hemisphere AIS. Delays to hospital admission from stroke onset to neuroimaging
were similar among right and left hemisphere AIS patients. Delay in transfer to
an acute stroke unit (ASU) following hospital admission was on average 14 hours
more for right hemisphere compared to left hemisphere AIS patients (P = .01).
Laterality was not associated with any difference in 10-year survival.
CONCLUSIONS: Patients with mild and nondominant AIS merit particular attention to
minimize their intrahospital transfer time to an ASU.
PMID- 27514581
TI - Cerebral Air Embolism with Pneumomediastinum Resulting from Emesis: A Case
Report.
AB - Cerebral air embolism (CAE) is a rare cause of stroke. Most cerebral air emboli
are caused by iatrogenic factors, such as invasive cardiac and pulmonary
procedures. Here, we report an unusual case of CAE not related to any medical
intervention. An 87-year-old woman became unresponsive after vomiting. A computed
tomography (CT) scan of the head 6 hours after the onset of the vomiting revealed
multiple air emboli, mainly in the watershed area between the right anterior and
middle cerebral arteries. Magnetic resonance imaging with T2* gradient echo
showed the air emboli as granular hypointensities. Diffusion-weighted imaging
revealed an area of hyperintensity along the cortical region of the right frontal
lobe. Head CT scans showed that the size and number of the air emboli rapidly
decreased on day 2 and disappeared on day 9. We also performed a chest CT and
found pneumomediastinum, which gradually improved over the clinical course. We
also found pulmonary fibrosis and bronchiectasis, suggesting an underlying
pulmonary vulnerability. In this case, the emesis may have been a trigger for the
CAE, which was followed by pneumomediastinum. This case suggests that CAE can
occur in a noniatrogenic situation, especially in a patient with pulmonary
vulnerability.
PMID- 27514582
TI - Computational neuroanatomy using brain deformations: From brain parcellation to
multivariate pattern analysis and machine learning.
AB - The past 20 years have seen a mushrooming growth of the field of computational
neuroanatomy. Much of this work has been enabled by the development and
refinement of powerful, high-dimensional image warping methods, which have
enabled detailed brain parcellation, voxel-based morphometric analyses, and
multivariate pattern analyses using machine learning approaches. The evolution of
these 3 types of analyses over the years has overcome many challenges. We present
the evolution of our work in these 3 directions, which largely follows the
evolution of this field. We discuss the progression from single-atlas, single
registration brain parcellation work to current ensemble-based parcellation; from
relatively basic mass-univariate t-tests to optimized regional pattern analyses
combining deformations and residuals; and from basic application of support
vector machines to generative-discriminative formulations of multivariate pattern
analyses, and to methods dealing with heterogeneity of neuroanatomical patterns.
We conclude with discussion of some of the future directions and challenges.
PMID- 27514583
TI - Research Methods in Healthcare Epidemiology: Survey and Qualitative Research.
AB - Surveys are one of the most frequently employed study designs in healthcare
epidemiology research. Generally easier to undertake and less costly than many
other study designs, surveys can be invaluable to gain insights into opinions and
practices in large samples and may be descriptive and/or be used to test
associations. In this context, qualitative research methods may complement this
study design either at the survey development phase and/or at the
interpretation/extension of results stage. This methods article focuses on key
considerations for designing and deploying surveys in healthcare epidemiology and
antibiotic stewardship, including identification of whether or not de novo survey
development is necessary, ways to optimally lay out and display a survey,
denominator measurement, discussion of biases to keep in mind particularly in
research using surveys, and the role of qualitative research methods to
complement surveys. We review examples of surveys in healthcare epidemiology and
antimicrobial stewardship and review the pros and cons of methods used. A
checklist is provided to help aid design and deployment of surveys in healthcare
epidemiology and antimicrobial stewardship. Infect Control Hosp Epidemiol 2016;1
6.
PMID- 27514585
TI - Optic nerve sheath diameter on computed tomography not predictive of neurological
status post-cardiac arrest.
AB - OBJECTIVE: Optic nerve sheath diameter (ONSD) measured on a head computed
tomography (CT) has been suggested as a potential prognostic factor for poor
neurological outcome after cardiac arrest. We performed a single centre
retrospective cohort analysis to further investigate this relationship. METHODS:
All patients >18 years of age admitted to St. Paul's Hospital in Vancouver,
Canada who survived a cardiac arrest and had a CT scan of the head within 48
hours were included in the analysis. RESULTS: A total of 72 patients met
inclusion criteria for the study; 54 (75.0%) of the patients had a poor
neurological outcome, whereas 18 (25.0%) patients were discharged from the
hospital with a good outcome. A CT head was obtained for patients in the good
outcome group in a mean time of 9.3 hours (SD 10.0) compared to 10.2 hours (SD
11.2) for the poor outcome group (p=0.75). There was no difference in average
ONSD observed between the two outcome groups (6.66 mm SD 0.78 v. 6.60 mm SD 0.82,
p=0.77). Multiple logistic regression failed to show any association between ONSD
and neurological outcome when adjusted for all other covariates (OR 1.32 95% CI
0.40-4.34, p=0.65). Setting an ONSD threshold of >8 mm (OR 2.32, 95% CI 0.14
39.40, p=0.55) or >7 mm (OR 0.28, 95% CI 0.03-2.77, p=0.28) also failed to show
any association on neurological outcome. CONCLUSION: There was no observed
difference in ONSD between those with a good neurological outcome and those with
a poor outcome. ONSD was not an independent predictor of poor neurological
outcome.
PMID- 27514584
TI - RUNX1 contributes to higher-order chromatin organization and gene regulation in
breast cancer cells.
AB - RUNX1 is a transcription factor functioning both as an oncogene and a tumor
suppressor in breast cancer. RUNX1 alters chromatin structure in cooperation with
chromatin modifier and remodeling enzymes. In this study, we examined the
relationship between RUNX1-mediated transcription and genome organization. We
characterized genome-wide RUNX1 localization and performed RNA-seq and Hi-C in
RUNX1-depleted and control MCF-7 breast cancer cells. RNA-seq analysis showed
that RUNX1 depletion led to up-regulation of genes associated with chromatin
structure and down-regulation of genes related to extracellular matrix biology,
as well as NEAT1 and MALAT1 lncRNAs. Our ChIP-Seq analysis supports a prominent
role for RUNX1 in transcriptional activation. About 30% of all RUNX1 binding
sites were intergenic, indicating diverse roles in promoter and enhancer
regulation and suggesting additional functions for RUNX1. Hi-C analysis of RUNX1
depleted cells demonstrated that overall three-dimensional genome organization is
largely intact, but indicated enhanced association of RUNX1 near Topologically
Associating Domain (TAD) boundaries and alterations in long-range interactions.
These results suggest an architectural role for RUNX1 in fine-tuning local
interactions rather than in global organization. Our results provide novel
insight into RUNX1-mediated perturbations of higher-order genome organization
that are functionally linked with RUNX1-dependent compromised gene expression in
breast cancer cells.
PMID- 27514586
TI - Lymphangioleiomyomatosis.
AB - Lymphangioleiomyomatosis is a rare multisystem disease predominantly affecting
women that can occur sporadically or in association with tuberous sclerosis. Lung
cysts progressively replace the lung parenchyma, which leads to dyspnea,
recurrent pneumothorax, and in some cases respiratory failure. Patients may also
have lymphatic disease in the thorax, abdomen, and pelvis, and renal
angiomyolipomas. Treatment includes supportive care, bronchodilators, and for
those with progressive disease, mammalian target of rapamycin (mTOR) inhibitors.
PMID- 27514587
TI - Plastic Bronchitis.
AB - Plastic bronchitis is an uncommon and probably underrecognized disorder,
diagnosed by the expectoration or bronchoscopic removal of firm, cohesive,
branching casts. It should not be confused with purulent mucous plugging of the
airway as seen in patients with cystic fibrosis or bronchiectasis. Few
medications have been shown to be effective and some are now recognized as
potentially harmful. Current research directions in plastic bronchitis research
include understanding the genetics of lymphatic development and maldevelopment,
determining how abnormal lymphatic malformations contribute to cast formation,
and developing new treatments.
PMID- 27514588
TI - Nonmalignant Adult Thoracic Lymphatic Disorders.
AB - The thoracic lymphatic disorders are a heterogeneous group of uncommon conditions
that are associated with thoracic masses, interstitial pulmonary infiltrates, and
chylous complications. Accurate diagnosis of the thoracic lymphatic disorders has
important implications for the newest approaches to management, including
embolization and treatment with antilymphangiogenic drugs. New imaging techniques
to characterize lymphatic flow, such as dynamic contrast-enhanced magnetic
resonance lymphangiogram, are redefining approaches to disease classification and
therapy.
PMID- 27514589
TI - Langerhans Cell Histiocytosis and Other Histiocytic Diseases of the Lung.
AB - Several histiocytic disorders may affect the thoracic cavity. Pulmonary
Langerhans cell histiocytosis (LCH) is the histiocytic disorder that most
frequently manifests with thoracic involvement in adults and is associated with
cigarette smoking. The histiocytic disorders follow variable clinical courses
ranging from benign disease to life-threatening aggressive disorders. Although
the pathogenesis is not fully understood, it is now apparent that some of these
disorders are associated with activating mutations in cell
proliferative/regulatory pathways. Management of these rare disorders must be
individualized. Pharmacologic treatment may include the use of chemotherapeutic
agents. Smoking cessation is imperative in the management of pulmonary LCH.
PMID- 27514590
TI - Pulmonary Alveolar Proteinosis Syndrome.
AB - Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by the
accumulation of surfactant in alveoli and terminal airways resulting in
respiratory failure. PAP comprises part of a spectrum of disorders of surfactant
homeostasis (clearance and production). The surfactant production disorders are
caused by mutations in genes required for normal surfactant production. The PAP
syndrome is identified based on history, radiologic, and bronchoalveolar lavage
and/or histopathologic findings. The diagnosis of PAP-causing diseases in
secondary PAP requires further studies. Whole-lung lavage is the current standard
therapy and promising new pharmacologic therapies are in development.
PMID- 27514591
TI - Pulmonary Alveolar Microlithiasis.
AB - Pulmonary alveolar microlithiasis (PAM) is a genetic lung disorder that is
characterized by the accumulation of calcium phosphate deposits in the alveolar
spaces of the lung. Mutations in the type II sodium phosphate cotransporter,
NPT2b, have been reported in patients with PAM. PAM progresses gradually, often
producing incremental dyspnea on exertion, desaturation in young adulthood, and
respiratory insufficiency by late middle age. Treatment remains supportive,
including supplemental oxygen therapy. For patients with end-stage disease, lung
transplantation is available as a last resort. The recent development of a
laboratory animal model has revealed several promising treatment approaches for
future trials.
PMID- 27514593
TI - Lymphocytic Interstitial Pneumonia.
AB - Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum
of benign pulmonary lymphoproliferative disorders. LIP is frequently associated
with connective tissue diseases or infections. Idiopathic LIP is rare; every
attempt must be made to diagnose underlying conditions when LIP is diagnosed.
Computed tomography of the chest in patients with LIP may reveal ground-glass
opacities, centrilobular and subpleural nodules, and randomly distributed thin
walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to
differentiating LIP from lymphoma. The 5-year mortality remains between 33% and
50% and is likely to vary based on the underlying disease process.
PMID- 27514594
TI - Birt-Hogg-Dube Syndrome.
AB - Birt-Hogg-Dube syndrome (BHD) is a rare autosomal dominant disorder caused by
mutations in the Folliculin gene and is characterized by the formation of
fibrofolliculomas, early onset renal cancers, pulmonary cysts, and spontaneous
pneumothoraces. The exact pathogenesis of tumor and lung cyst formation in BHD
remains unclear. There is great phenotypic variability in the clinical features
of BHD, and patients can present with any combination of skin, pulmonary, or
renal findings. More than 80% of adult patients with BHD have pulmonary cysts on
high-resolution computed tomography scan of the chest.
PMID- 27514592
TI - Primary Ciliary Dyskinesia.
AB - Primary ciliary dyskinesia (PCD) is a recessive genetically heterogeneous
disorder of motile cilia with chronic otosinopulmonary disease and organ
laterality defects in ~50% of cases. The prevalence of PCD is difficult to
determine. Recent diagnostic advances through measurement of nasal nitric oxide
and genetic testing has allowed rigorous diagnoses and determination of a robust
clinical phenotype, which includes neonatal respiratory distress, daily nasal
congestion, and wet cough starting early in life, along with organ laterality
defects. There is early onset of lung disease in PCD with abnormal airflow
mechanics and radiographic abnormalities detected in infancy and early childhood.
PMID- 27514595
TI - alpha1-Antitrypsin Deficiency.
AB - alpha1-Antitrypsin deficiency is an autosomal codominant condition that
predisposes to emphysema and cirrhosis. The condition is common but grossly under
recognized. Identifying patients' alpha1-antitrypsin deficiency has important
management implications (ie, smoking cessation, genetic and occupational
counseling, and specific treatment with the infusion of pooled human plasma
alpha1-antitrypsin). The weight of evidence suggests that augmentation therapy
slows the progression of emphysema in individuals with severe alpha1-antitrypsin
deficiency.
PMID- 27514597
TI - Hereditary Hemorrhagic Telangiectasia.
AB - Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized and
underdiagnosed autosomal-dominant angiodysplasia that has an estimated prevalence
of 1 in 5000 individuals, with variable clinical presentations even within family
members with identical mutations. The most common manifestations are
telangiectasias of the skin and nasal mucosa. However, HHT can often be
complicated by the presence of arteriovenous malformations and telangiectasias in
the lungs, brain, gastrointestinal tract, and liver that are often silent and can
lead to life-threatening complications of stroke and hemorrhage. This article
reviews HHT for the pulmonologist, who is not uncommonly the first practitioner
to encounter these patients.
PMID- 27514596
TI - Hermansky-Pudlak Syndrome.
AB - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is
associated with oculocutaneous albinism, bleeding diatheses, granulomatous
colitis, and highly penetrant pulmonary fibrosis in some subtypes, including HPS
1, HPS-2, and HPS-4. HPS pulmonary fibrosis shows many of the clinical,
radiologic, and histologic features found in idiopathic pulmonary fibrosis, but
occurs at a younger age. Despite knowledge of the underlying genetic defects,
there are currently no definitive therapeutic or preventive approaches for HPS
pulmonary fibrosis other than lung transplant.
PMID- 27514598
TI - Pulmonary Capillary Hemangiomatosis and Pulmonary Veno-occlusive Disease.
AB - This article provides an overview of pulmonary veno-occlusive disease (PVOD) and
pulmonary capillary hemangiomatosis (PCH), two disorders that challenge
clinicians, radiologists, and pathologists because they often mimic pulmonary
arterial hypertension (PAH). The article reviews the features that differentiate
PVOD and PCH from PAH. The article also describes the overlap of PVOD and PCH,
highlighted by recent reports of families diagnosed with PVOD or PCH caused by
EIF2AK4 mutations. In addition, the article outlines current approaches to the
diagnosis and treatment of PVOD and PCH.
PMID- 27514599
TI - Eosinophilic Lung Diseases.
AB - Eosinophilic lung diseases especially comprise eosinophilic pneumonia or as the
more transient Loffler syndrome, which is most often due to parasitic infections.
The diagnosis of eosinophilic pneumonia is based on characteristic clinical
imaging features and the demonstration of alveolar eosinophilia, defined as at
least 25% eosinophils at BAL. Peripheral blood eosinophilia is common but may be
absent at presentation in idiopathic acute eosinophilic pneumonia, which may be
misdiagnosed as severe infectious pneumonia. All possible causes of eosinophilia,
including drug, toxin, fungus related etiologies, must be thoroughly
investigated. Extrathoracic manifestations should raise the suspicion of
eosinophilic granulomatosis with polyangiitis.
PMID- 27514601
TI - Immunoglobulin G4-Related Disease and the Lung.
AB - Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory
disease with protean manifestations involving virtually any organ in the body. At
initial clinical presentation, 1 or multiple organs may be involved. Initial
descriptions focused on pancreatic disease. It has, however, become clear that
IgG4-RD can cause an immune-mediated fibroinflammatory process, commonly
manifesting as mass-like lesions, in various regions of the body including the
thorax where any compartment can be involved. This pathologic process is
characterized by infiltration of IgG4+ plasma cells and a propensity to fibrosis
leading to organ dysfunction which can be prevented by early diagnosis and
corticosteroid therapy.
PMID- 27514600
TI - Hyper-IgE Syndromes and the Lung.
AB - Elevated serum IgE has many etiologies including parasitic infection, allergy and
asthma, malignancy, and immune dysregulation. The hyper-IgE syndromes caused by
mutations in STAT3, DOCK8, and PGM3 are monogenic primary immunodeficiencies
associated with high IgE, eczema, and recurrent infections. These primary
immunodeficiencies are associated with recurrent pneumonias leading to
bronchiectasis; however, each has unique features and genetic diagnosis is
essential in guiding therapy, discussing family planning, and defining prognosis.
This article discusses the clinical features of these primary immunodeficiencies
with a particular focus on the pulmonary manifestations and discussion of the
genetics, pathogenesis, and approaches to therapy.
PMID- 27514602
TI - Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Neuroendocrine
Hyperplasia of Infancy.
AB - Although incidental reactive pulmonary neuroendocrine cell hyperplasia (PNECH) is
seen on biopsy specimens in adults with chronic lung disease, disorders
characterized by marked PNECH are rare. Primary hyperplasia of neuroendocrine
cells in the lung and obstructive lung disease related to remodeling or
physiologic constriction of small airways define diffuse idiopathic
neuroendocrine cell hyperplasia (DIPNECH) in the adult and neuroendocrine cell
hyperplasia of infancy (NEHI) in children. DIPENCH and NEHI share a similar
physiology, typical imaging appearance, and increased neuroendocrine cells on
biopsy. However, there are important differences related to the underlying
disease mechanisms leading to disparate outcomes.
PMID- 27514603
TI - Benign Metastasizing Leiomyoma.
AB - Benign metastasizing leiomyoma (BML) is a rare and poorly characterized disease
affecting primarily premenopausal women. Asymptomatic patients are often
diagnosed incidentally by radiographs or other lung-imaging procedures performed
for other indications, and the diagnosis is eventually confirmed by biopsy.
Patients with BML are usually treated pharmacologically with antiestrogen
therapies or surgically with oophorectomy or hysterectomy. Antiestrogen therapy
is typically efficacious and, in general, most patients have a favorable
prognosis. Asymptomatic patients with a confirmed diagnosis of BML, may be
followed conservatively without treatment.
PMID- 27514604
TI - Rare Lung Diseases: Occasionally the "Horse" Has Stripes.
PMID- 27514605
TI - Genitourinary infections in diabetic patients in the new era of diabetes therapy
with sodium-glucose cotransporter-2 inhibitors.
AB - AIMS: To review prevalence and significance of urinary tract (UTI) and genital
infections (GI) in diabetes and the effects of sodium glucose cotransporter 2
(SGLT-2) inhibitors on these complications. DATA SYNTHESIS: The prevalence of
asymptomatic bacteriuria (ASB) is 2-3 times higher in diabetic than in non
diabetic women. The treatment of ASB has no impact on the development of UTIs
and/or a decline in renal function. Therefore, there is no indication for
screening for and/or treatment of ASB. The incidence of UTI is higher and
frequently complicated in diabetic patients, particularly in those with longer
duration of disease and of older age. There is no consistent evidence of an
association between A1c levels, glycosuria and the risk of ASB and/or UTIs.
Diabetes is a known risk factor for Candida colonization and GI, and a poor
glycemic control is associated with a higher risk. While patients treated with
SGLT-2 inhibitors may have a non-significant increased risk of UTI, they have a
clearly increased risk of GI; most of these infections are mild, easy to treat,
and the rate of recurrence is low. CONCLUSION: Diabetic patients are at high risk
of UTIs and of GI. Only GI are associated with poor glycemic control. Although
patients treated with SGLT-2 inhibitors have an increased 3-5 fold risk of GI,
proper medical education can reduce this risk.
PMID- 27514607
TI - Dietary fat intake modifies the influence of the FTO rs9939609 polymorphism on
adiposity in adolescents: The HELENA cross-sectional study.
AB - BACKGROUND AND AIMS: The fat mass and obesity associated gene (FTO) has been
associated with obesity and dietary intake. The aims were: (i) To assess whether
energy and macronutrient intakes were different across the FTOrs9939609 genotypes
in adolescents, and (ii) to explore whether dietary fat intake modified the
association of the rs9939609 polymorphism with adiposity. METHODS AND RESULTS:
The FTOrs9939609 polymorphism was genotyped in 652 adolescents (53% females, 14.8
+/- 1.2 years, TT = 246, TA = 296, AA = 110). Energy and macronutrient intake
were assessed by two non-consecutive 24 h-recalls. Weight, height, waist
circumference and skinfold thicknesses were measured and body fat percent was
calculated. Energy and macronutrient intake were similar across the FTOrs9939609
genotypes (P > 0.2). There were significant interactions between the FTO
polymorphism and fat intake on adiposity estimates (P < 0.05). In adolescents
whose fat intake was below 30% (N = 203), the A allele of rs9939609 was not
associated with adiposity indices. In contrast, in adolescents whose fat intake
was between 30% and 35% of energy (N = 190), the rs9939609 polymorphism was
associated with a 1.9% higher body fat per risk allele (95%CI: 0.39, 3.33; P <
0.05), and in those whose fat intake was higher than 35% (N = 259), it was
associated with a 2.8% higher body fat per risk allele (95%CI: 1.27, 4.43; P <
0.001). CONCLUSIONS: These findings support the concept that the deleterious
effect of the FTOrs9939609 polymorphism on adiposity is exacerbated in
adolescents consuming high fat diets. In contrast, the consumption of low fat
diets (<30% of energy) may attenuate the genetic predisposition to obesity in
risk allele carriers.
PMID- 27514606
TI - The association of calcium supplementation and incident cardiovascular events in
the Multi-ethnic Study of Atherosclerosis (MESA).
AB - BACKGROUND AND AIMS: Many US adults use calcium supplements to address inadequate
dietary intake and improve bone health. However, recent reports have suggested
that use of calcium supplements may elevate cardiovascular disease (CVD) risk. In
this study, we examined associations between baseline calcium supplement use and
incident myocardial infarction (MI) (n = 208 events) and CVD events (n = 641
events) over 10.3 years in men and women from the Multi-Ethnic Study of
Atherosclerosis (MESA) cohort (n = 6236), with dietary calcium intake at baseline
also examined as a supplementary objective. METHODS AND RESULTS: Using Cox
proportional hazards models, no compelling associations between calcium intake
from supplements or diet and incident CVD events were observed upon multivariate
adjustment for potential confounders. An association with lower MI risk was
observed comparing those with low levels of calcium supplement use (1-499 mg) to
those using no calcium supplements (hazard ratio 0.69, 95% CI 0.48, 0.98, p =
0.039). Relationships were homogeneous by gender, race/ethnicity, or chronic
kidney disease. Results were also similar when the analysis was limited to
postmenopausal women only. CONCLUSION: Analysis of incident MI and CVD events in
the MESA cohort does not support a substantial association of calcium supplement
use with negative cardiovascular outcomes.
PMID- 27514608
TI - Lp(a) and cardiovascular risk: Investigating the hidden side of the moon.
AB - AIMS: This article reports current evidence on the association between Lp(a) and
cardiovascular (CV) disease and on pathophysiological mechanisms. The available
information on therapy for reduction of lipoprotein(a) is also discussed. DATA
SYNTHESIS: Although some evidence is conflicting, Lp(a) seems to increase CV risk
through stimulation of platelet aggregation, inhibition of tissue factor pathway
inhibitor, alteration of fibrin clot structure and promotion of endothelial
dysfunction and phospholipid oxidation. Lp(a) 3.5-fold higher than normal
increases the risk of coronary heart disease and general CV events, particularly
in those with LDL cholesterol >= 130 mg/dl. High Lp(a) values represent also an
independent risk factor for ischemic stroke (more relevant in young stroke
patients), peripheral artery disease (PAD) and aortic and mitral stenosis.
Furthermore, high Lp(a) levels seem to be associated with increased risk of
cardiovascular events in patients with chronic kidney disease, particularly in
those undergoing percutaneous coronary intervention. CONCLUSIONS: Lipoprotein (a)
(Lp[a]) seems to significantly influence the risk of cardiovascular events. The
effects of statins and fibrates on Lp(a) are limited and extremely variable.
Nicotinic acid was shown effective in reducing Lp(a) but, due to its side effects
and serious adverse events during clinical trials, it is no longer considered a
possible option for treatment. To date, the treatment of choice for high levels
of Lp(a) in high CV risk patients is represented by LDL-Apheresis. Thanks to
innovative technologies, new selectively inhibiting LPA drugs are being developed
and tested.
PMID- 27514609
TI - Erratum to: Autonomic nervous system involvement in the giant axonal neuropathy
(GAN) KO mouse: implications for human disease.
PMID- 27514610
TI - Heterologous expression of antigenic peptides in Bacillus subtilis biofilms.
AB - BACKGROUND: Numerous strategies have been developed for the display of
heterologous proteins in the surface of live bacterial carriers, which can be
used as vaccines, immune-modulators, cancer therapy or bioremediation. Bacterial
biofilms have emerged as an interesting approach for the expression of proteins
of interest. Bacillus subtilis is a well-described, endospore-forming organism
that is able to form biofilms and also used as a probiotic, thus making it a
suitable candidate for the display of heterologous proteins within the biofilm.
Here, we describe the use of TasA, an important structural component of the
biofilms formed by B. subtilis, as a genetic tool for the display of heterologous
proteins. RESULTS: We first engineered the fusion protein TasA-mCherry and showed
that was widely deployed within the B. subtilis biofilms. A significant
enhancement of the expression of TasA-mCherry within the biofilm was obtained
when depleting both tasA and sinR genes. We subsequently engineered fusion
proteins of TasA to antigenic peptides of the E. granulosus parasite, paramyosin
and tropomyosin. Our results show that the antigens were well expressed within
the biofilm as denoted by macrostructure complementation and by the detection of
the fusion protein in both immunoblot and immunohistochemistry. In addition, we
show that the recombinant endospores of B. subtilis preserve their biophysical
and morphological properties. CONCLUSIONS: In this work we provide strong
evidence pointing that TasA is a suitable candidate for the display of
heterologous peptides, such as antigens, cytokines, enzymes or antibodies, in the
B. subtilis biofilms. Finally, our data portray that the recombinant endospores
preserve their morphological and biophysical properties and could be an excellent
tool to facilitate the transport and the administration.
PMID- 27514611
TI - Heart rate variability in chronic low back pain patients randomized to yoga or
standard care.
AB - BACKGROUND: Chronic pain can alter the autonomic balance with increased
sympathetic activity reflected in altered heart rate variability (HRV). It has
been proposed that yoga can be useful to correct the autonomic imbalance in
patients with chronic pain who have reduced HRV. METHODS AND DESIGNS: In the
present randomized controlled trial 62 patients with chronic low back pain
associated with altered alignment of intervertebral discs (aged between 20 and 45
years, 32 males) were randomized to 2 groups. One group received yoga for 3
months while the other group carried out standard medical care based on the
physician's advice. The duration was the same, i.e., 3 months. The heart rate
variability and rate of respiration were assessed at baseline and at the end of 3
months. RESULTS: There was a significant difference in the baseline (pre) values
between groups (p = 0.008) for respiration rate which was higher in the yoga
group. The changes reported below are pre-post comparisons within each group. The
yoga group showed a significant (p < 0.05; repeated measures ANOVA, post-hoc
analyses) decrease in the LF power of HRV, rate of respiration and a significant
increase in the HF power of HRV and in the pNN50. CONCLUSION: The results suggest
that yoga practice can shift the autonomic balance towards vagal dominance in
patients with chronic low back pain associated with altered alignment of
intervertebral discs. TRIAL REGISTRATION: The study is registered with the
Clinical Trials Registry of India ( CTRI/2012/11/003094 ) and can be accessed at.
PMID- 27514612
TI - Basin entropy: a new tool to analyze uncertainty in dynamical systems.
AB - In nonlinear dynamics, basins of attraction link a given set of initial
conditions to its corresponding final states. This notion appears in a broad
range of applications where several outcomes are possible, which is a common
situation in neuroscience, economy, astronomy, ecology and many other
disciplines. Depending on the nature of the basins, prediction can be difficult
even in systems that evolve under deterministic rules. From this respect, a
proper classification of this unpredictability is clearly required. To address
this issue, we introduce the basin entropy, a measure to quantify this
uncertainty. Its application is illustrated with several paradigmatic examples
that allow us to identify the ingredients that hinder the prediction of the final
state. The basin entropy provides an efficient method to probe the behavior of a
system when different parameters are varied. Additionally, we provide a
sufficient condition for the existence of fractal basin boundaries: when the
basin entropy of the boundaries is larger than log2, the basin is fractal.
PMID- 27514616
TI - Blister fluid and serum cytokine levels in severe sepsis in humans reflect skin
dysfunction.
AB - BACKGROUND: Knowledge of sepsis-related end-organ inflammation in vivo is
limited. We investigated the cytokine response in skin and in serum in sepsis and
its relation to multiorgan failure (MOF) and survival. METHODS: Cytokines were
analysed in serum and in suction blister fluid of intact skin of 44 patients with
severe sepsis and 15 healthy controls. Blister fluid and serum samples were
collected within 48 h of the first sepsis-induced organ failure. This is a
substudy of a larger follow-up study on wound healing in sepsis. RESULTS:
Cytokine levels were higher in patients with sepsis vs. controls (interleukin
[IL]-10, blisters: 65.9 vs. 4.3 pg/ml, P < 0.001, serum: 25.7 vs. 4.5 pg/ml, P =
0.004; IL-6, blisters: 41.9 vs. 0.03 pg/ml, P < 0.001, serum: 45.5 vs. 2.1 pg/ml,
P < 0.001). Patients with MOF had higher levels of IL-10 (116.4 vs. 21.3 pg/ml, P
= 0.015), IL-4 (0.7 vs. 0.07 pg/ml, P = 0.013) and basic fibroblast growth factor
(bFGF) (25.9 vs. 9.5 pg/ml, P = 0.027) in blister fluid than patients without
MOF. In blister fluid, survivors had lower levels of IL-10 (43.3 vs. 181.9 pg/ml,
P = 0.024) and bFGF (15.8 vs. 31.9 pg/ml, P = 0.006) than non-survivors. In
serum, survivors had higher levels of vascular endothelial growth factor (VEGF)
(152.2 vs. 14.7 pg/ml, P = 0.012) and lower levels of IL-6 (38.5 vs. 91.1 pg/ml,
P = 0.011) than non-survivors. The blister fluid levels of bFGF, TNF and VEGF did
not correlate with the serum levels. CONCLUSIONS: Cytokine responses in skin
blister fluid in patients with sepsis differed from those in healthy controls.
PMID- 27514617
TI - The Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel in Healthy
Japanese Volunteers.
AB - The dosing regimen of prasugrel adjusted for Japanese patients was compared with
that of clopidogrel by analyzing the pharmacokinetics and pharmacodynamics in 40
healthy Japanese subjects in a randomized, single-blind crossover study. In
period 1, the subjects received either 300 mg clopidogrel or 20 mg prasugrel;
after a >2-week interval (period 2), the drug was switched. Blood samples of 36
of the 40 subjects were collected for analysis of pharmacokinetics,
pharmacodynamics, and CYP2C19 genotypes. The plasma concentration of the active
metabolite of prasugrel increased rapidly and reached its peak 30 minutes
postadministration, whereas that of the active metabolite of clopidogrel reached
its peak 1 hour postadministration. The mean AUC and Cmax of the active
metabolite of clopidogrel, but not those of prasugrel, were CYP2C19 genotype
dependent. Prasugrel rapidly inhibited platelet aggregation, reaching its maximum
effect 1 hour postadministration. Clopidogrel, on the other hand, showed maximum
inhibition 2 hours postadministration. Platelet aggregation inhibition by
clopidogrel was significantly lower in the poor-metabolizer subjects than in the
extensive-metabolizer subjects. Overall, prasugrel inhibited platelet aggregation
more rapidly and more effectively in healthy Japanese subjects than was observed
for clopidogrel.
PMID- 27514619
TI - Reflectance confocal microscopy as a noninvasive complementary tool in the
diagnosis of psoriatic balanitis.
PMID- 27514618
TI - Vaccinating with conserved Escherichia coli antigens does not alter the mouse
intestinal microbiome.
AB - BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrheal disease.
Antigenic and structural heterogeneity among ETEC colonization factors has
complicated vaccine development efforts. Identifying and characterizing conserved
ETEC antigens that induce protective immunity is therefore of interest. We
previously characterized three proteins (MipA, Skp, and ETEC_2479) that protected
mice in an intranasal ETEC challenge model after vaccination. However, these
proteins are conserved not only in multiple ETEC isolates, but also in commensal
bacteria. While the impact of inactivated viral vaccines and live-attenuated
bacterial vaccines on the host microbiota have been examined, the potential
impact of using subunit vaccines consisting of antigens that are also encoded by
commensal organisms has not been investigated. FINDINGS: We addressed this issue
by characterizing changes to mouse intestinal microbiomes as a function of
vaccination. We failed to observe significant changes to mouse health, to mouse
weight gain as a function of time, or to the diversity or richness of mouse
intestinal microbiomes, as measured by analyzing alpha- and beta-diversity, as
well as overall community structure, before and after vaccination. CONCLUSIONS:
We conclude that despite the conservation of MipA, Skp, and ETEC_2479 among Gram
negative bacteria, vaccination with these antigens fails to alter significantly
the host intestinal microbiome.
PMID- 27514620
TI - Parental attitudes towards measles vaccination in the canton of Aargau,
Switzerland: a latent class analysis.
AB - BACKGROUND: Despite the successes of routine national childhood vaccination
programmes, measles remains a public health concern. The purpose of this paper is
to investigate how patterns of parental attitudes are linked to the decision
making process for or against MMR vaccination. This exploratory study was
designed to identify distinct patterns of attitudes towards or against measles
vaccination through Latent Class Analysis (LCA) in a sub-sample of mothers living
in the canton of Aargau in Switzerland. METHODS: Parents of young children below
36 months of age were randomly selected through parents' counsellors' registries.
Among other questions, respondents were asked to state their agreement in
response to 14 belief statements regarding measles vaccination on a 5-point
Likert scale. To identify groups of parents showing distinct patterns of
attitudes and beliefs regarding measles vaccination, we used Latent Class
Analysis (LCA). RESULTS: The LCA showed three classes of parents with different
attitudes and believes towards measles vaccination: The biggest group (class 1)
are those having positive attitudes towards immunisation, followed by the second
biggest group (class 2) which is characterised by having fearful attitudes and by
showing uncertainty about immunisation. The third group (class 3) shows distinct
patterns of critical attitudes against immunisation. Within this group over 90 %
agree or totally agree that immunisation is an artificial intrusion into the
natural immune system and therefore want to vaccinate their children only if
necessary. CONCLUSION: We find that parents in the Canton Aargau who hesitate to
vaccinate their children against measles, mumps and rubella show distinct
opinions and attitudes. Health professionals should be aware of these perceptions
to tailor their messages accordingly and positively influence these parents to
vaccinate their children. Special attention needs to be given to those parents
who are planning to vaccinate their children but are not following the national
guidelines.
PMID- 27514622
TI - Transthyretin Cardiac Amyloidosis: From Rare Monogenic Disease to Common Pathway
in Heart Failure?
PMID- 27514621
TI - Household air pollution and the lung microbiome of healthy adults in Malawi: a
cross-sectional study.
AB - BACKGROUND: Domestic combustion of biomass fuels, such as wood, charcoal, crop
residue and dung causes Household Air Pollution (HAP). These inhaled particulates
affect more than half of the world's population, causing respiratory problems
such as infection and inflammatory lung disease. We examined whether the presence
of black carbon in alveolar macrophages was associated with alterations in the
lung microbiome in a Malawi population. METHODS: Bronchoalveolar lavage samples
from 44 healthy adults were sequenced using 16S rDNA amplification to assess
microbial diversity, richness and relative taxa abundance. Individuals were
classified as high or low particulate exposure as determined by questionnaire and
the percentage of black carbon within their alveolar macrophages. RESULTS:
Subjects in the low and high particulate groups did not differ in terms of source
of fuels used for cooking or lighting. There was no difference in alpha or beta
diversity by particulate group. Neisseria and Streptococcus were significantly
more abundant in samples from high particulate exposed individuals, and
Tropheryma was found less abundant. Petrobacter abundance was higher in people
using biomass fuel for household cooking and lighting, compared with exclusive
use of electricity. CONCLUSIONS: Healthy adults in Malawi exposed to higher
levels of particulates have higher abundances of potentially pathogenic bacteria
(Streptococcus, Neisseria) within their lung microbiome. Domestic biomass fuel
use was associated with an uncommon environmental bacterium (Petrobacter)
associated with oil-rich niches.
PMID- 27514623
TI - Immunosuppressive Therapy and Interferon-1beta in Acute Myocarditis.
PMID- 27514624
TI - Atrioventricular Conduction Disorder as a First Manifestation of Arrhythmogenic
Right Ventricular Dysplasia.
PMID- 27514625
TI - Complex Coarctation and Anomalous Right Subclavian Artery.
PMID- 27514626
TI - Introduction.
PMID- 27514627
TI - Non-vitamin K oral anticoagulant treatment in elderly patients with atrial
fibrillation and coronary heart disease.
AB - Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Overall
prevalence is estimated to 5.5% and the incidence increases with age. As the
population ages, the prevalence and costs of AF are expected to increase. AF is
the most important cause of stroke in patients >75years. Until recently, Vitamin
K antagonists (VKAs) were the only available oral anticoagulants (OACs) evaluated
for long-term treatment of patients with AF with or without coronary heart
disease (CHD). This situation was challenged by introduction of non-VKA oral
anticoagulants (NOACs). In AF, use of NOACs seems to be as effective and safe as
VKAs, especially in elderly patients. AF and CHD are frequently associated and
the question of antithrombotic management in aging patients is delicate. In
elderly patients experiencing a new AF episode after an acute coronary syndrome,
triple antithrombotic therapy should be as short as possible in order to decrease
the risk of major bleedings. To date, there is no specific study or available
guidelines regarding the NOACs use specifically in elderly patients experiencing
both AF and CHD. In this review, we try to provide a perspective on NOACs future
incorporation into clinical practice in elderly patients with both AF and CHD.
PMID- 27514628
TI - Invasive versus conservative strategy in acute coronary syndromes: The paradox in
women's outcomes.
AB - BACKGROUND: We explored benefits and risks of an early invasive compared with a
conservative strategy in women versus men after non-ST elevation acute coronary
syndromes (NSTE-ACS) using the ISACS-TC database. METHODS: From October 2010 to
May 2014, 4145 patients were diagnosed as having a NSTE-ACS. We excluded 258
patients managed with coronary bypass surgery. Of the remaining 3887 patients,
1737 underwent PCI (26% women). The primary endpoint was the composite of 30-day
mortality and severe left ventricular dysfunction defined as an ejection fraction
<40% at discharge. RESULTS: Women were older and more likely to exhibit more risk
factors and Killip Class >=2 at admission as compared with men. In patients who
underwent PCI, peri-procedural myocardial injury was not different among sexes
(3.1% vs. 3.2%). Women undergoing PCI experienced higher rates of the composite
endpoint (8.9% vs. 4.9%, p=0.002) and 30-day mortality (4.4% vs. 2.0%, p=0.008)
compared with men, whereas those who managed with only routine medical therapy
(RMT) did not show any sex difference in outcomes. In multivariable analysis,
female sex was associated with favorable outcomes (adjusted HR for the composite
endpoint: 0.72, 95% CI: 0.58-0.91) in patients managed with RMT, but not in those
undergoing PCI (adjusted HR: 0.96, 95% CI: 0.61-1.52). CONCLUSIONS: We observed a
more favorable outcome in women than men when patients were managed with RMT.
Women and men undergoing PCI have similar outcomes. These data suggest caution in
extrapolating the results from men to women in an overall population of patients
in the context of different therapeutic strategies.
PMID- 27514630
TI - The effects of caregiver and household HIV on child development: a community
based longitudinal study of young children.
AB - OBJECTIVE: Many studies that document child outcomes in the context of parental
HIV - which has been established as a risk factor for child development - focus
on older children/adolescents. Studies also concentrate on the status of the
primary caregiver, not other household members who might be infected. DESIGN:
This study examined the effects of caregiver and household HIV on child
development (4-13 years) in South Africa and Malawi (2011-2014). METHODS: Data
were gathered from 989 children and their primary caregivers at baseline and
repeated at 12-15 months follow-up (86.5% follow-up rate). Only caregivers of a
single child and caregiver/child dyads without missing data were included,
providing a sample of 808 dyads for analysis. Children were divided into three
groups according to caregiver-reported HIV burden: having an HIV-positive primary
caregiver (19.8%), having HIV in the household (14.2%) or no HIV (66%). RESULTS:
The HIV burden was positively associated with an array of negative child
outcomes, often mediated by caregiver depression levels. Family HIV burden at
baseline affected child behavioural problems at follow-up indirectly through
carer depression (B = 0.02; CI = 0.003, 0.06). Internalizing (B = 0.02; CI =
0.002, 0.05) and externalizing problems at follow-up (B = 0.01; CI = 0.0002,
0.03) were also indirectly affected by family HIV burden through caregiver
depression. CONCLUSIONS: The data suggest that family HIV can affect child
development, emphasizing the important role of depression in the pathway to such
an effect. Community-based interventions directed at alleviating parental
depression in the presence of HIV may help to interrupt the cycle of family HIV
and adverse child outcomes.
PMID- 27514631
TI - A public health perspective to environmental barriers and accessibility problems
for senior citizens living in ordinary housing.
AB - BACKGROUND: Housing environments that hinder performance of daily activities and
impede participation in social life have negative health consequences
particularly for the older segment of the population. From a public health
perspective accessible housing that supports active and healthy ageing is
therefore crucial. The objective of the present study was to make an inventory of
environmental barriers and investigate accessibility problems in the ordinary
housing stock in Sweden as related to the functional capacity of senior citizens.
Particular attention was paid to differences between housing types and building
periods and to identify environmental barriers generating the most accessibility
problems for sub-groups of senior citizens. METHODS: Data on environmental
barriers in dwellings from three databases on housing and health in old age was
analysed (N = 1021). Four functional profiles representing large groups of senior
citizens were used in analyses of the magnitude and severity of potential
accessibility problems. Differences in terms of type of housing and building
period were examined. RESULTS: High proportions of one-family houses as well as
multi-dwellings had substantial numbers of environmental barriers, with
significantly lower numbers in later building periods. Accessibility problems
occurred already for senior citizens with few functional limitations, but more
profound for those dependent on mobility devices. The most problematic housing
sections were entrances in one-family houses and kitchens of multi-dwellings.
CONCLUSIONS: Despite a high housing standard in the Swedish ordinary housing
stock the results show substantial accessibility problems for senior citizens
with functional limitations. To make housing accessible large-scale and
systematic efforts are required.
PMID- 27514632
TI - Immediate and early complications of the open Latarjet procedure: a retrospective
review of a large consecutive case series.
AB - BACKGROUND: Immediate and early postoperative complications of the Latarjet
procedure are not well documented in the literature. The purpose of this study
was to report the procedure-related complications of our large consecutive case
series of 3 surgeons at a single high-volume center. METHODS: We conducted a
retrospective chart review of 416 Latarjet procedures performed on 400 patients
(16 patients had bilateral procedures) who underwent surgery by the 3 senior
authors from October 2002 to July 2015. Immediate and early complications
included hardware problems, infection, and neurologic injury. In addition, the
patient's age and history of prior instability surgery were noted and evaluated
as risk factors for complication. RESULTS: The overall complication rate was 5.0%
(21 complications in 19 procedures). Thirteen neurologic injuries (3.1%) occurred
to the axillary (7), musculocutaneous (4), and suprascapular (2) nerves,
including 2 patients with multiple nerves affected. All but 2 patients had
complete resolution of symptoms at time of last follow-up. Six infections (1.4%)
developed, including 3 superficial infections treated with oral antibiotics and 3
deep infections requiring irrigation and debridement with intravenous
antibiotics. Two early hardware-related complications (0.05%) were also noted.
Increased age was associated with a higher complication rate. History of prior
surgery was not associated with increased complications in our series.
CONCLUSIONS: This study highlights the procedural complications of the Latarjet
procedure. Neurologic injury was the most common complication in our series, with
complete or near-complete recovery in 11 of 13 patients.
PMID- 27514629
TI - A randomised controlled trial of adjunctive yoga and adjunctive physical exercise
training for cognitive dysfunction in schizophrenia.
AB - BACKGROUND: Yoga and physical exercise have been used as adjunctive intervention
for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are
lacking. Aims A single-blind randomised controlled trial was designed to evaluate
whether yoga training or physical exercise training enhance cognitive functions
in SZ, based on a prior pilot study. METHODS: Consenting, clinically stable,
adult outpatients with SZ (n=286) completed baseline assessments and were
randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or
supervised physical exercise training with TAU (PE). Based on the pilot study,
the primary outcome measure was speed index for the cognitive domain of
'attention' in the Penn computerised neurocognitive battery. Using mixed models
and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and
6 months post-training were evaluated with intention-to-treat paradigm. RESULTS:
Speed index of attention domain in the YT group showed greater improvement than
PE at 6 months follow-up (p<0.036, effect size 0.51). In the PE group, 'accuracy
index of attention domain showed greater improvement than TAU alone at 6-month
follow-up (p<0.025, effect size 0.61). For several other cognitive domains,
significant improvements were observed with YT or PE compared with TAU alone
(p<0.05, effect sizes 0.30-1.97). CONCLUSIONS: Both YT and PE improved attention
and additional cognitive domains well past the training period, supporting our
prior reported beneficial effect of YT on speed index of attention domain. As
adjuncts, YT or PE can benefit individuals with SZ.
PMID- 27514633
TI - Introducing the Surgical Therapeutic Index in trauma surgery: an assessment tool
for the benefits and risks of operative fracture treatment strategies.
AB - BACKGROUND: The Surgical Therapeutic Index (STI) has been described as an
indicator of the benefits and risks of surgical treatment. The index is
calculated by dividing the cure rate of an operative treatment by the
complication rate. This study introduces the STI in trauma surgery by comparing
the indices for surgical plate fixation (PF) and intramedullary fixation (IMF) of
displaced midshaft clavicular fractures. METHODS: In a previously reported,
randomized controlled fashion, 120 patients were assigned to PF or IMF. Cure was
defined by a Disabilities of the Arm, Shoulder and Hand score of 8 or less.
Complications were noted as present or not present for each follow-up assessment,
and a panel of experts provided weights to the severity of complications. STIs
were reported along with their 95% confidence intervals. The higher a procedure's
STI, the higher the benefit/risk balance of that procedure. RESULTS: The
nonweighted STI after 6 weeks was significantly higher in the PF group. During
further follow- up, the differences leveled out and became nonsignificant. When
weighting the STI for severity, the indices decrease but are significantly in
favor of the PF group at 6 weeks and 6 months after surgery. At 1 year
postoperatively, differences are not significant. CONCLUSION: The STI may be a
reliable tool to assess the benefits and risks of operative fracture treatment.
Further studies with consistent results of this new scoring system are needed
before conclusions can be generalized. When determining the indices of PF and
IMF, a significant difference in favor of PF was observed during the early phase
of recovery.
PMID- 27514634
TI - Safety and efficacy of shoulder arthroplasty following lower extremity
periprosthetic joint infection.
AB - BACKGROUND: The safety of arthroplasty in patients with a previous periprosthetic
joint infection (PJI) remains unclear. The objective of this study was to
determine whether patients with a history of a properly treated PJI complicating
lower extremity arthroplasty can safely undergo shoulder arthroplasty without an
increased risk of shoulder infection or compromise in their clinical outcomes.
METHODS: Between 2002 and 2013, 36 patients with successful treatment of an
infected lower extremity arthroplasty underwent a subsequent primary shoulder
arthroplasty. Three were lost to follow-up. The remaining 33 shoulders were
analyzed at a mean follow-up of 3.5 years for radiographic, clinical, and
functional outcomes. Nine patients were receiving chronic antibiotic suppression
at the time of their index shoulder arthroplasty. The mean time between PJI
treatment and shoulder arthroplasty was 4.7 years (range, 0.7-13.1 years).
RESULTS: Shoulder arthroplasty led to improved pain scores and range of motion.
Excellent or satisfactory modified Neer ratings were achieved in 78.8% of
patients. There was no difference in American Shoulder and Elbow Surgeons scores
between the groups with and without chronic antibiotic suppression. There were 2
reoperations, both in patients not receiving chronic suppression. The indications
were aseptic glenoid loosening and infection after a periprosthetic fracture. The
final estimated survival free of infection was 93.3%. DISCUSSION/CONCLUSION:
Shoulder arthroplasty in patients with a history of PJI complicating hip or knee
arthroplasty seems to be safe, with a low rate of infection. Thus, previous lower
extremity PJI should not be considered a relative contraindication to shoulder
arthroplasty.
PMID- 27514635
TI - Regarding "Metal-backed glenoid implant with polyethylene insert is not a viable
long-term therapeutic option".
PMID- 27514636
TI - Management of acute or late hematogenous infection after shoulder arthroplasty
with irrigation, debridement, and component retention.
AB - BACKGROUND: Irrigation and debridement (I&D) with component retention is an
appealing alternative to both patients and surgeons for the management of acute
or late hematogenous deep periprosthetic shoulder infection (PSI). However, the
success rate and results of I&D are poorly documented. This study reports the
outcomes and complications of this treatment strategy for acute and delayed-onset
acute hematogenous PSI. METHODS: Between 1980 and 2010, 10 shoulders (9 patients)
underwent I&D with component retention for the management on an acute or delayed
onset acute hematogenous PSI at a single institution. Outcome data, including
pain, range of motion, need for chronic oral antibiotic suppression therapy,
eradication of infection, and need for further surgery were retrospectively
collected. RESULTS: Deep infection recurred in 3 shoulders, which were eventually
treated with resection arthroplasty. Of the remaining 6 patients (7 shoulders), 5
were prescribed chronic antibiotic suppression. At the most recent follow-up,
pain was graded as none in 3 shoulders, mild in 1, moderate with activity in 3,
moderate in 2, and severe in 1. Among shoulders with retained components, forward
elevation was greater than 110 degrees in 6 (median, 140 degrees ; range, 30
degrees -160 degrees ), and external rotation was greater than 40 degrees in all
shoulders (median, 50 degrees ; range, 40 degrees -90 degrees ). CONCLUSION: I&D
allowed component retention in 70% of shoulders presenting with an acute or
delayed-onset acute hematogenous infection. Most patients were prescribed chronic
antibiotic suppression, and reasonable motion was maintained.
PMID- 27514637
TI - Mixed neuropathy presenting clinically as an anterior interosseous nerve palsy
following shoulder arthroscopy: a report of four cases.
AB - BACKGROUND: Anterior interosseous nerve (AIN) palsies can arise spontaneously or
be attributed to one of many causes. We present 4 cases, the largest series to
date, in which a mixed peripheral neuropathy presented primarily as an AIN palsy
following ipsilateral shoulder arthroscopy. In this report, we detail the
patient's presenting symptoms, describe our management of the complication, and
provide hypotheses for the mechanism behind the complication. METHODS: Four
different surgeons performed the initial arthroscopic surgeries, but the senior
author in all cases managed follow-up and treatment of the neuropathy. All
patients were informed and agreed to have their cases published. RESULTS: All
four patients experienced significant recovery, although 2 of 4 required AIN
decompression and exploration because of failure to improve with conservative
management. CONCLUSION: Whereas variables such as position, index surgical
procedure, and use of regional anesthesia varied among our patients, the one
constant was the fluid extravasation from the arthroscopy itself, and for this
reason we believe that if there is one singular cause to explain all of these
neuropathies, it would be increased pressure in the upper arm and forearm from
fluid extravasation in patients with at-risk anatomy. Outside of prevention,
recognizing this complication and providing appropriate intervention or referral
to a surgeon capable of appropriate intervention are important for any surgeon
performing shoulder arthroscopies.
PMID- 27514638
TI - Structural and morphological peculiarities of hybrid Au/nanodiamond engineered
nanostructures.
AB - Nanostructured Au nano-platelets have been synthesized from an Au(III) complex by
growth process triggered by nanodiamond (ND). An electroless synthetic route has
been used to obtain 2D Au/ND architectures, where individual nanodiamond
particles are intimately embedded into face-centered cubic Au platelets. The
combined use of high resolution transmission electron microscopy (HR-TEM) and
selected area electron diffraction (SAED), was able to reveal the unusual
organization of these hybrid nanoparticles, ascertaining the existence of
preferential crystallographic orientations for both nanocrystalline species and
highlighting their mutual locations. Detailed information on the sample
microstructure have been gathered by fast Fourier transform (FFT) and inverse
fast Fourier transform (IFFT) of HR-TEM images, allowing us to figure out the
role of Au defects, able to anchor ND crystallites and to provide specific sites
for heteroepitaxial Au growth. Aggregates constituted by coupled ND and Au,
represent interesting systems conjugating the best optoelectronics and plasmonics
properties of the two different materials. In order to promote realistically the
applications of such outstanding Au/ND materials, the cooperative mechanisms at
the basis of material synthesis and their influence on the details of the hybrid
nanostructures have to be deeply understood.
PMID- 27514639
TI - Robotic splenectomy with ex vivo bench surgery and hemi-spleen autotransplant:
the first report.
AB - BACKGROUND: We describe our experience with what is, to our knowledge, the first
case of robotic assisted ex vivo partial splenectomy with auto-transplantation
for a benign non parasitic cyst. MATERIALS AND METHODS: The patient is a 32 year
old female with a giant, benign splenic cyst causing persistent abdominal pain.
Preoperative imaging showed a cystic lesion measuring 8.3 * 7.6 cm, in the middle
portion of the spleen. Due to the central location of the bulky lesion a partial
splenectomy was not feasible. As an alternative to a total splenectomy, a
possible reimplantation of hemi-spleen after bench surgery was offered. We
proceeded with a robotic total splenectomy and bench hemisplenectomy, preserving
the lower pole and a portion of the middle segment of the organ. A robotic
reconstruction of the splenic vessels was then performed intra-abdominally. The
reperfusion was optimal. RESULTS: The total operative time was 305 min, with 78
min of robotic time. Postoperative ultrasound confirmed a patent arterial and
venous flow. The postoperative course was uneventful and the patient was
discharged on postoperative day 4. The pathology report was consistent with
epithelial cyst of the spleen. The patient is doing well at 6-month follow-up.
CONCLUSIONS: The optimized vision and dexterity provided by the robotic system
allowed a safe and precise reconstruction of the splenic vessels, even in a deep
and narrow operative field. Partial splenectomy with autotransplantation of the
organ was thus achieved, avoiding a total splenectomy in a young patient.
PMID- 27514640
TI - Factors Influencing ACT After Intravenous Bolus Administration of 100 IU/kg of
Unfractionated Heparin During Cardiac Catheterization in Children.
AB - Anticoagulation using intravenous bolus administration of unfractionated heparin
(UFH) aims to prevent thromboembolic complications in children undergoing cardiac
catheterization (CC). Optimal UFH dosage is needed to reduce bleeding
complications. We analyzed the effect of bolus UFH on activated clotting time
(ACT) in children undergoing CC focusing on age-dependent, anesthesia-related, or
disease-related influencing factors. This retrospective single-center study of
183 pediatric patients receiving UFH during CC analyzed ACT measured at the end
of CC. After bolus administration of 100 IU UFH/kg body weight, ACT values
between 105 and 488 seconds were reached. Seventy-two percent were within target
level of 160 to 240 seconds. Age-dependent differences were not obtained ( P =
.407). The ACT values were lower due to hemodilution (total fluid and crystalloid
administration during CC, both P < .001), with premedication of acetylsalicylic
acid ( P = .014) and low-molecular-weight heparin ( P = .049). Arterial
thrombosis (3.85%), venous thrombosis (0.55%), and bleeding (1.65%) following CC
did not correlate with ACT values but occurred more frequently in children
between 1 month and 1 year of age (91%). In conclusion, with a bolus of 100 IU
UFH/kg, an ACT target level of 160 to 240 seconds can be achieved during CC in
children in 72%, which is influenced by hemodilution and anticoagulant and
antiplatelet premedication but not by age.
PMID- 27514641
TI - GP recruits offered L20 000 to train in Scotland.
PMID- 27514642
TI - The Impact of Primary Aggressor Laws on Single Versus Dual Arrest in Incidents of
Intimate Partner Violence.
AB - To combat the concern that mandatory arrest laws have resulted in officers
unjustly arresting victims, states have enacted primary aggressor laws. Examining
3,078 incidents of intimate partner violence reported to the police in 25
jurisdictions in four states, the authors assess the impact of primary aggressor
laws on the likelihood of both single and dual arrest. While dual arrests were
more than twice as likely in a state without a primary arrest statute, an arrest
was nearly a third less likely in a state with such a statute. The policy
implications are discussed.
PMID- 27514643
TI - Mechanisms Associated with Activation of Intracellular Metabotropic Glutamate
Receptor, mGluR5.
AB - The group 1 metabotropic glutamate receptor, mGluR5, is found on the cell surface
as well as on intracellular membranes where it can mediate both overlapping and
unique signaling effects. Previously we have shown that glutamate activates
intracellular mGluR5 by entry through sodium-dependent transporters and/or
cystine glutamate exchangers. Calibrated antibody labelling suggests that the
glutamate concentration within neurons is quite high (~10 mM) raising the
question as to whether intracellular mGluR5 is maximally activated at all times
or whether a different ligand might be responsible for receptor activation. To
address this issue, we used cellular, optical and molecular techniques to show
that intracellular glutamate is largely sequestered in mitochondria; that the
glutamate concentration necessary to activate intracellular mGluR5 is about ten
fold higher than what is necessary to activate cell surface mGluR5; and uncaging
caged glutamate within neurons can directly activate the receptor. Thus these
studies further the concept that glutamate itself serves as the ligand for
intracellular mGluR5.
PMID- 27514644
TI - Upregulation of PSMB4 is Associated with the Necroptosis after Spinal Cord
Injury.
AB - Spinal cord injury (SCI) is one of the most common and severe complications in
spine injury. It is difficult to prevent cell necroptosis and promote the
survival of residual neurons after SCI. Proteasome beta-4 subunit (PSMB4) is the
first proteasomal subunit with oncogenic properties promoting cancer cell
survival and tumor growth in vivo, and our previous study showed that PSMB4 is
significantly associated with neuronal apoptosis in neuroinflammation. However,
PSMB4 function in the necroptosis after SCI is unkown. RIP3, a key regulatory
factor of necroptosis, correlates with the induction of necroptosis in various
types of cells and signaling pathway. Upregulation of the RIP3 expression may
play a role as a novel molecular mechanism in secondary neural tissue damage
following SCI. In this study, we established an acute spinal cord contusion
injury model in adult rats to investigate the potential role of PSMB4 during the
pathological process of SCI. We found PSMB4 expression was significantly up
regulated 3 days after injury by western blot and immunohistochemical staining.
Double immunofluorescent staining indicated obvious changes of PSMB4 expression
occurred in neurons. Significant up-regulation of PSMB4 expression was observed
in Rip3 positive neurons at 3 days after SCI, which indicated that PSMB4 might
play a vital role in the regulation of Rip3. Overexpress and knockdown PSMB4
could intervene the RIP3 and Mixed lineage kinase domain-like protein (MLKL)
pathway in Tumor necrosis factor-alpha (TNF-alpha) induced necroptosis cell
model. Based on our experimental data, we boldly conclude that PSMB4 is
associated with RIP3 involved necroptosis after SCI.
PMID- 27514645
TI - Waiting time for radiation therapy after breast-conserving surgery in early
breast cancer: a retrospective analysis of local relapse and distant metastases
in 615 patients.
AB - BACKGROUND: Postoperative radiotherapy after breast-conserving surgery (BCS) is
the standard in the management of breast cancer. The optimal timing for starting
postoperative radiation therapy has not yet been well defined. In this study, we
aimed to evaluate if the time interval between BCS and postoperative radiotherapy
is related to the incidence of local and distant relapse in women with early node
negative breast cancer not receiving chemotherapy. METHODS: We retrospectively
analyzed clinical data concerning 615 women treated from 1984 to 2010, divided
into three groups according to the timing of radiotherapy: <=60, 61-120, and >120
days. To estimate the presence of imbalanced distribution of prognostic and
treatment factors among the three groups, the chi2 test or the Fisher exact test
were performed. Local relapse-free survival, distant metastasis-free survival
(DMFS), and disease-free survival (DFS) were estimated with the Kaplan-Meier
method, and multivariate Cox regression was used to test for the independent
effect of timing of RT after adjusting for known confounding factors. The median
follow-up time was 65.8 months. RESULTS: Differences in distribution of age, type
of hormone therapy, and year of diagnosis were statistically significant. At 15
year follow-up, we failed to detect a significant correlation between time
interval and the risk of local relapse (p = 0.09) both at the univariate and the
multivariate analysis. The DMFS and the DFS univariate analysis showed a
decreased outcome when radiotherapy was started early (p = 0.041 and p = 0.046),
but this was not confirmed at the multivariate analysis (p = 0.406 and p = 0.102,
respectively). CONCLUSIONS: Our results show that no correlation exists between
the timing of postoperative radiotherapy and the risk of local relapse or distant
metastasis development in a particular subgroup of women with node-negative early
breast cancer.
PMID- 27514647
TI - Hepatitis C virus prevention and treatment prioritization-ethical, economic and
evidential dimensions of early rather than delayed treatment for people who
inject drugs.
PMID- 27514646
TI - MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent
seizures.
AB - BACKGROUND: Recurrent convulsions can cause irreversible astrocyte death, impede
neuron regeneration, and further aggravate brain damage. MicroRNAs have been
revealed as players in the progression of numerous diseases including cancer and
Alzheimer's disease. Particularly, microRNA has been found linked to seizure
induced neuronal death. In this study, a rat model of recurrent convulsions
induced by flurothyl treatments was utilised to assess the alterations of
microRNA expressions in hippocampus tissues. We also applied an in vitro model in
which primary astrocytes were exposed to kainic acid to verify the targets of miR
34b-5p identified in the animal model. RESULTS: We discovered that miR-34b-5p, a
member of the miR-34 family, increased significantly in flurothyl-treated rat
hippocampus tissue. More surprisingly, this upregulation occurred concurrently
with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p
in seizures caused astrocyte apoptosis. Results from the in vitro experiments
further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA,
translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by
influencing Bcl-2, Bax, and Caspase-3. CONCLUSION: Our findings prove microRNAs
play a role in mediating recurrent convulsions-induced astrocyte death and
further indicate that miR-34b-5p could acts as a regulator for astrocyte
apoptosis induced by recurrent seizures.
PMID- 27514648
TI - BCL2 and MYC are expressed at high levels in canine diffuse large B-cell lymphoma
but are not predictive for outcome in dogs treated with CHOP chemotherapy.
AB - Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic
malignancy in dogs. Recently, MYC and BCL2 expression levels determined with
immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We
hypothesized that canine DLBCL can be similarly subdivided into prognostic
subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with
CHOP chemotherapy were retrospectively collected and 43 dogs had available
histologic tissue and complete clinical follow-up. Median values of percent
immunoreactive versus immunonegative cells were used to determine positive or
negative expression status. Completion of CHOP was significantly associated with
a positive outcome. Compared with human patients, our canine DLBCL patients had
high IHC expression of both MYC and BCL2, and relative expression levels of one
or both markers were not associated with clinical outcome.
PMID- 27514649
TI - Triple-Quadrupole Inductively Coupled Plasma-Mass Spectrometry with a High
Efficiency Sample Introduction System for Ultratrace Determination of (135)Cs and
(137)Cs in Environmental Samples at Femtogram Levels.
AB - High yield fission products, (135)Cs and (137)Cs, have entered the environment as
a result of anthropogenic nuclear activities. Analytical methods for ultratrace
measurement of (135)Cs and (137)Cs are required for environmental geochemical and
nuclear forensics studies. Here we report a highly sensitive method combining a
desolvation sample introduction system (APEX-Q) with triple-quadrupole
inductively coupled plasma mass spectrometry (AEPX-ICPMS/MS) for the
determination of (135)Cs and (135)Cs/(137)Cs isotope ratio at femtogram levels.
Using this system, we introduced only selected ions into the collision/reaction
cell to react with N2O, significantly reducing the isobaric interferences
((135)Ba(+) and (137)Ba(+)) and polyatomic interferences ((95,97)Mo(40)Ar(+),
(119)Sn(16)O(+), and (121)Sb(16)O(+)). Compared to the instrument setup of
ICPMS/MS, the APEX-ICPMS/MS enables a 10-fold sensitivity increase. In addition,
an effective chemical separation scheme consisting of ammonium molybdophosphate
(AMP) Cs-selective adsorption and two-stage ion-exchange chromatographic
separation was developed to remove major matrix and interfering elements from
environmental samples (10-40 g). This separation method showed high
decontamination factors (10(4)-10(7)) for major matrix elements (Al, Ca, K, Mg,
Na, and Si) and interfering elements (Ba, Mo, Sb, and Sn). The high sensitivity
of APEX-ICPMS/MS and the effective removal sample matrix allowed reliable
analysis of (135)Cs and (137)Cs with extremely low detection limits (0.002 pg mL(
1), corresponding to 0.006 Bq mL(-1) (137)Cs). The accuracy and applicability of
the APEX-ICPMS/MS method was validated by analysis of seven standard reference
materials (soils, sediment, and plants). For the first time, ultratrace
determination of (135)Cs and (135)Cs/(137)Cs isotope ratio at global fallout
source environmental samples was achieved with the ICPMS technique.
PMID- 27514650
TI - Laser Refrigeration of Ytterbium-Doped Sodium-Yttrium-Fluoride Nanowires.
AB - Sodium yttrium fluoride (beta-NaYF4 ) nanowires (NWs) with a hexagonal crystal
structure are synthesized using a low-cost hydrothermal process and are shown to
undergo laser refrigeration based on an upconversion process leading to anti
Stokes (blueshifted) photoluminescence. Single-beam laser trapping combined with
forward light scattering is used to investigate cryophotonic laser refrigeration
of individual NWs through analysis of their local Brownian dynamics.
PMID- 27514651
TI - From the Editor.
PMID- 27514652
TI - Target blood pressure for patients with hypertension: lower blood pressure is not
better.
PMID- 27514653
TI - Type 1 and 3 inositol trisphosphate receptors are required for extra-embryonic
vascular development.
AB - The embryonic-maternal interface of the placental labyrinth, allantois, and yolk
sac are vital during embryogenesis; however, the precise mechanism underlying the
vascularization of these structures remains unknown. Herein we focus on the role
of inositol 1,4,5-trisphosphate (IP3) receptors (IP3R), which are intracellular
Ca(2+) release channels, in placentation. Double knockout (DKO) of type 1 and 3
IP3Rs (IP3R1 and IP3R3, respectively) in mice resulted in embryonic lethality
around embryonic day (E) 11.5. Because IP3R1 and IP3R3 were co-expressed in
endothelial cells in the labyrinth, allantois, and yolk sac, we investigated
extra-embryonic vascular development in IP3R1- and IP3R3-DKO mice. The formation
of chorionic plates and yolk sac vessels seemed dysregulated around the timing of
the chorio-allantoic attachment, immediately followed by the disorganization of
allantoic vessels, the decreased expression of the spongiotrophoblast cell marker
Tpbpa and the growth retardation of the embryos in DKO mice. Fluorescent
immunohistochemistry demonstrated downregulation of a vascular endothelial
marker, CD31, in labyrinth embryonic vessels and poor elongation of extra
embryonic mesoderm into the labyrinth layer in DKO placenta, whereas the
branching of the DKO chorionic trophoblast was initiated. In addition, allantoic
and yolk sac vessels in extra-embryonic tissues were less remodeled in DKO mice.
In vitro endothelial cord formation and migration activities of cultured vascular
endothelial cells derived from human umbilical vein were downregulated under the
inhibition of IP3R. Our results suggest that IP3R1 and IP3R3 are required for
extra-embryonic vascularization in the placenta, allantois, and yolk sac. This is
the first demonstration of the essential role of IP3/IP3Rs signaling in the
development of the vasculature at the embryonic-maternal interface.
PMID- 27514654
TI - Automating quality assurance of digital linear accelerators using a
radioluminescent phosphor coated phantom and optical imaging.
AB - Performing mechanical and geometric quality assurance (QA) tests for medical
linear accelerators (LINAC) is a predominantly manual process that consumes
significant time and resources. In order to alleviate this burden this study
proposes a novel strategy to automate the process of performing these tests. The
autonomous QA system consists of three parts: (1) a customized phantom coated
with radioluminescent material; (2) an optical imaging system capable of
visualizing the incidence of the radiation beam, light field or lasers on the
phantom; and (3) software to process the captured signals. The radioluminescent
phantom, which enables visualization of the radiation beam on the same surface as
the light field and lasers, is placed on the couch and imaged while a predefined
treatment plan is delivered from the LINAC. The captured images are then
processed to self-calibrate the system and perform measurements for evaluating
light field/radiation coincidence, jaw position indicators, cross-hair centering,
treatment couch position indicators and localizing laser alignment. System
accuracy is probed by intentionally introducing errors and by comparing with
current clinical methods. The accuracy of self-calibration is evaluated by
examining measurement repeatability under fixed and variable phantom setups. The
integrated system was able to automatically collect, analyze and report the
results for the mechanical alignment tests specified by TG-142. The average
difference between introduced and measured errors was 0.13 mm. The system was
shown to be consistent with current techniques. Measurement variability increased
slightly from 0.1 mm to 0.2 mm when the phantom setup was varied, but no
significant difference in the mean measurement value was detected. Total
measurement time was less than 10 minutes for all tests as a result of
automation. The system's unique features of a phosphor-coated phantom and fully
automated, operator independent self-calibration offer the potential to
streamline the QA process for modern LINACs.
PMID- 27514655
TI - Bioactive gentixanthone and gentichromone from the whole plants of Gentianella
acuta (Michx.) Hulten.
AB - Five new compounds, gentixanthones A1 (1), A2 (2), and gentichromones A1-A3 (3
5), together with thirteen known xanthones (6-18) were obtained from the whole
plants of Gentianella acuta (Michx.) Hulten. Their structures were elucidated by
chemical and spectroscopic methods. Among them, compounds 6, 8, 13, 14, and 17
were obtained from Gentianella genus firstly, and 7, 12, 15, 16, and 18 were
isolated from this plant for the first time. Meanwhile, inhibitory effects of 1
18 on motility of mouse isolated intestine tissue were determined. As results,
xanthones 1, 2, 6, 7, 9, 10 and 14 were found to have significant reduce effect
on intestine contraction tension, and structure-activity relationship was
discussed.
PMID- 27514656
TI - Quality profile determination of Chios mastic gum essential oil and detection of
adulteration in mastic oil products with the application of chiral and non-chiral
GC-MS analysis.
AB - The determination of mastic oil profile, with emphasis on its chiral
characteristics, could serve as a method for detecting adulteration in products
found in the market with a claim of mastic oil content aiming towards protecting
it from counterfeiting. Furthermore the evaluation of the raw material is
crucial, as the profile is potentially affected by factors as mastic origin and
storage time. Thus 45 authentic mastic oil samples were analyzed by GC-MS
employing a chiral column and content limits for all major constituents were
determined. The chiral GC-MS analysis proved that selected concentration ratios
between these constituents, namely those of (-)/(+)-alpha-pinene (<=1:100) and (
)-alpha-pinene/myrcene (1.9:100-11:100) could serve as markers for the
determination of mastic oil authenticity. Employing this methodology, the
analysis of 25 mastic oils contained in cosmetic and dietary products, as well as
an artificial mastic oil sample, exhibited several differentiations that could
indicate adulteration either with artificial essential oils or volatile
compounds, or the use of aged mastic oil.
PMID- 27514657
TI - Extended Culture of Encapsulated Human Blastocysts in Alginate Hydrogel
Containing Decidualized Endometrial Stromal Cells in the Presence of Melatonin.
AB - Extended in vitro culture of human embryos beyond blastocyst stage could serve as
a tool to explore the molecular and physiological mechanisms underlying embryo
development and to identify factors regulating pregnancy outcomes. This study
presents the first report on the maintenance of human embryo in vitro by alginate
co-encapsulation of human blastocyst and decidualized endometrial stromal cells
(EnSCs) under melatonin-fortified culture conditions. The effectiveness of the 3D
culture system was studied through monitoring of embryo development in terms of
survival time, viability, morphological changes, and production of the two
hormones of 17b-oestradiol and human chorionic gonadotropin. The embryo
structural integrity was preserved during alginate encapsulation; however, only
23 % of the encapsulated embryos could retain in the hydrogels over time and
survived until day 4 post-encapsulation. The culture medium fortification with
melatonin significantly elevated the maintenance rate of expanded embryos in
alginate beads by 65 % and prolonged survival time of human embryos to day 5.
Furthermore, embryo co-culture with EnSCs using melatonin-fortified medium
increased the survival time of encapsulated embryos to 44 %. The levels of two
measured hormones significantly rose at day 4 in comparison with day 2 post
encapsulation especially in the group co-encapsulated with EnSCs and cultivated
in melatonin-fortified culture medium. These data are the first evidence
representing in vitro development of human embryos until day 10 post
fertilization. This achievement can facilitate the investigation of the
mechanisms regulating human embryo development.
PMID- 27514658
TI - ESR1, ERBB2, and Ki67 mRNA expression predicts stage and grade of non-muscle
invasive bladder carcinoma (NMIBC).
AB - Pathological staging and grading are crucial for risk assessment in non-muscle
invasive bladder cancer (NMIBC). Molecular grading might support pathological
evaluation and minimize interobserver variability. In this study, the well
established breast cancer markers ESR1, PGR, ERBB2, and MKI67 were evaluated as
potential molecular markers to support grading and staging in NMIBC. We
retrospectively analyzed clinical data and formalin-fixed paraffin-embedded
tissues (FFPE) of patients with NMIBC. Messenger RNA (mRNA) expression of the
aforementioned markers was measured by single-step reverse transcription
quantitative real-time polymerase chain reaction (RT-qPCR) using RNA-specific
TaqMan assays. Relative gene expression was determined by normalization to two
reference genes (CALM2 and B2M) using the 40-DeltaDeltaCT method and correlated
to histopathological stage and grade. Pathological assessment was performed by an
experienced uropathologist. Statistical analysis was performed using the SAS
software JMP 9.0.0 version and GraphPad Prism 5.04. Of 381 cases of NMIBC,
samples of 100 pTa and 255 pT1 cases were included in the final study. Spearman
rank correlation revealed significant correlations between grade and expression
of MKI67 (r = 0.52, p < 0.0001), ESR1 (r = 0.25, p < 0.0001), and ERBB2 (r =
0.18, p = 0.0008). In Mann-Whitney tests, MKI67 was significantly different
between all grades (p < 0.0001), while ESR1 (p = 0.0006) and ERBB2 (p = 0.027)
were significantly different between G2 and G3. Higher expression of MKI67 (r =
0.49; p < 0.0001), ERBB2 (r = 0.22; p < 0.0001), and ESR1 (r = 0.18; p = 0.0009)
mRNA was positively correlated with higher stage. MKI67 (p < 0.0001), ERBB2 (p =
0.0058), and PGR (p = 0.0007) were significantly different between pTa and pT1.
In NMIBC expression of ESR1, ERBB2 and MKI67 are significantly different between
stage and grade. This potentially provides objective parameters for pathological
evaluation.
PMID- 27514660
TI - Models of reablement evaluation (MoRE): a study protocol of a quasi-experimental
mixed methods evaluation of reablement services in England.
AB - BACKGROUND: Reablement is a time-limited intervention that aims to support people
to regain independence and enable them to resume their daily activities after
they return home from an in-patient care setting, or to maintain independence to
enable them to remain at home. There is some evidence that reablement can enhance
independence and has the potential to contain costs. However, reablement services
are funded and provided in different ways and by different organisations, and
there is limited research evidence about the effectiveness of different
reablement service models. This study will evaluate the effectiveness and cost
effectiveness of different reablement service models and service users' and
carers' experiences of reablement in England, UK. METHODS/DESIGN: The study will
use a quasi-experimental mixed methods design that comprises three work packages
(WP) extending over a period of 34 months. WP1 will conduct cluster analysis on
survey data to develop a typology of current models of reablement services in
order to describe the current reablement service landscape. WP2 will comprise a
quantitative outcomes evaluation of the effectiveness of the different service
models; a process evaluation and an economic evaluation. WP2 will be set within
generic reablement services, where providers are using the most commonly employed
generic reablement service types identified in WP1; the primary outcome measure
is health-related quality of life measured by the EQ-5D-5L. WP3 will provide
evidence about specialist reablement services and how specialist approaches and
practices are organised and delivered. DISCUSSION: Managing demands on care
services is, and will remain, a crucial factor for the UK National Health Service
as the number of people with long-term conditions rise. There has been, and will
continue to be, significant investment in reablement services. The proposed study
will address several key areas where there is limited evidence regarding the
organisation and delivery of reablement services in England, UK. Specifically, it
will provide new evidence on different models of reablement services that will be
of direct benefit to health and social care managers, commissioners and their
partner organisations.
PMID- 27514659
TI - Determining the mode of action of anti-mycobacterial C17 diyne natural products
using expression profiling: evidence for fatty acid biosynthesis inhibition.
AB - BACKGROUND: The treatment of microbial infections is becoming increasingly
challenging because of limited therapeutic options and the growing number of
pathogenic strains that are resistant to current antibiotics. There is an urgent
need to identify molecules with novel modes of action to facilitate the
development of new and more effective therapeutic agents. The anti-mycobacterial
activity of the C17 diyne natural products falcarinol and panaxydol has been
described previously; however, their mode of action remains largely undetermined
in microbes. Gene expression profiling was therefore used to determine the
transcriptomic response of Mycobacterium smegmatis upon treatment with falcarinol
and panaxydol to better characterize the mode of action of these C17 diynes.
RESULTS: Our analyses identified 704 and 907 transcripts that were differentially
expressed in M. smegmatis after treatment with falcarinol and panaxydol
respectively. Principal component analysis suggested that the C17 diynes exhibit
a mode of action that is distinct to commonly used antimycobacterial drugs.
Functional enrichment analysis and pathway enrichment analysis revealed that cell
processes such as ectoine biosynthesis and cyclopropane-fatty-acyl-phospholipid
synthesis were responsive to falcarinol and panaxydol treatment at the
transcriptome level in M. smegmatis. The modes of action of the two C17 diynes
were also predicted through Prediction of Activity Spectra of Substances (PASS).
Based upon convergence of these three independent analyses, we hypothesize that
the C17 diynes inhibit fatty acid biosynthesis, specifically phospholipid
synthesis, in mycobacteria. CONCLUSION: Based on transcriptomic responses, it is
suggested that the C17 diynes act differently than other anti-mycobacterial
compounds in M. smegmatis, and do so by inhibiting phospholipid biosynthesis.
PMID- 27514662
TI - Antagonist pharmacology of desensitizing and non-desensitizing nicotinic
acetylcholine receptors in cockroach neurons.
AB - Two alpha-bungarotoxin-sensitive nicotinic acetylcholine (ACh) receptor subtypes
in neurons of the American cockroach have been identified as desensitizing
(nAChD) and selectively inhibitable with 100nM imidacloprid, and non
desensitizing (nAChN) and selectively inhibitable with 100pM methyllycaconitine.
In this paper, the single-electrode voltage-clamp technique was used to measure
concentration-response relations for the action of ACh and five antagonists on
pharmacologically separated nAChD and nAChN receptors of acutely dissociated
neurons from thoracic ganglia of the American cockroach. A dual bath and U-tube
perfusion system was used to achieve rapid application of ACh in the continued
presence of antagonists, which was essential to accurately measure inhibition by
rapidly-reversible antagonists. ACh activated both receptors with an EC50 of 7MUM
and the antagonist potencies were (nAChD/nAChN in nM): dihydro-beta-erythroidine:
1.0/5.6, d-tubocurarine: 1000/34, condelphine: 0.39/0.65, phencyclidine: 74/980
and mecamylamine 47/1150. While each of these antagonists displayed some subtype
selectivity, none are selective enough to be used as subtype-selective tools.
These results bring to a total of 16 the number of nicotinic compounds that have
been measured on nAChD and nAChN currents. Characterization of these receptors is
important for understanding the role of nAChRs in the insect nervous system and
the mechanism of action of insecticides.
PMID- 27514663
TI - Significance of oxygen carriers and role of liquid paraffin in improving
validamycin A production.
AB - Validamycin A (Val-A) synthesized by Streptomyces hygroscopicus 5008 is widely
used as a high-efficient antibiotic to protect plants from sheath blight disease.
A novel fermentation strategy was introduced to stimulate Val-A production by
adding oxygen carriers. About 58 % increase in Val-A production was achieved
using liquid paraffin. Further, biomass, carbon source, metabolic genes, and
metabolic enzymes were studied. It was also found that the supplementation of
liquid paraffin increased the medium dissolved oxygen and intracellular oxidative
stress level. The expression of the global regulators afsR and soxR sensitive to
ROS, ugp catalyzing synthesis of Val-A precursor, and Val-A structural genes was
enhanced. The change of the activities of glucose-6-phosphate dehydrogenase and
glyceraldehyde 3-phosphate dehydrogenase was observed, which reflected the
redirection of carbon metabolic flux. Based on these results, liquid paraffin
addition as an oxygen carrier could be a useful technique in industrial
production of Val-A and our study revealed a redox-based secondary metabolic
regulation in S. hygroscopicus 5008, which provided a new insight into the
regulation of the biosynthesis of secondary metabolites.
PMID- 27514664
TI - Correlated positions in protein evolution and engineering.
AB - Statistical analysis of a protein multiple sequence alignment can reveal groups
of positions that undergo interdependent mutations throughout evolution. At these
so-called correlated positions, only certain combinations of amino acids appear
to be viable for maintaining proper folding, stability, catalytic activity or
specificity. Therefore, it is often speculated that they could be interesting
guides for semi-rational protein engineering purposes. Because they are a
fingerprint from protein evolution, their analysis may provide valuable insight
into a protein's structure or function and furthermore, they may also be suitable
target positions for mutagenesis. Unfortunately, little is currently known about
the properties of these correlation networks and how they should be used in
practice. This review summarises the recent findings, opportunities and pitfalls
of the concept.
PMID- 27514665
TI - Potential application of glycerol in the production of plant beneficial
microorganisms.
AB - This review highlights the importance of research for development of
biofertilizer and biocontrol products based on the use of glycerol for further
process scale-up to industrial microbiology. Glycerol can be used successfully in
all stages of production of plant beneficial microorganisms. It serves as an
excellent substrate in both submerged and solid-state fermentation processes with
free and immobilized microbial cells. Glycerol is also one of the most attractive
formulation agents that ensures high cell density and viability including in
harsh environmental conditions. Future research is discussed to make this
inexpensive material a base for industrial production of plant beneficial
microorganisms.
PMID- 27514666
TI - Bioprocess development for extracellular production of recombinant human
interleukin-3 (hIL-3) in Pichia pastoris.
AB - Human interleukin-3 (hIL-3) is a therapeutically important cytokine involved in
the maturation and differentiation of various cells of the immune system. The
codon-optimized hIL-3 gene was cloned in fusion with the N-terminus alpha-mating
factor signal peptide of Saccharomyces cerevisiae under an inducible alcohol
oxidase 1 (AOX1) and constitutive glyceraldehyde-3-phosphate dehydrogenase (GAP)
promoter. A Zeocin concentration up to 2000 mg/L was used to select hyper
producers. The shake flask cultivation studies in the Pichia pastoris GS115 host
resulted a maximum recombinant hIL-3 expression level of 145 mg/L in the
extracellular medium under the control of AOX1 promoter. The batch fermentation
strategy allowed us to attain a fairly pure glycosylated hIL-3 protein in the
culture supernatant at a final concentration of 475 mg/L with a high volumetric
productivity of 4.39 mg/L/h. The volumetric product concentration achieved at
bioreactor level was 3.28 folds greater than the shake flask results. The 6x His
tagged protein was purified using Ni-NTA affinity chromatography and confirmed
further by western blot analysis using anti-6x His tag antibody. The
glycosylation of recombinant hIL-3 protein was confirmed in a PNGase F
deglycosylation reaction where it showed a molecular weight band pattern similar
to E. coli produced non-glycosylated hIL-3 protein. The structural properties of
recombinant hIL-3 protein were confirmed by CD and fluorescence spectroscopy
where protein showed 40 % alpha-helix, 12 % beta-sheets with an emission maxima
at 343 nm. MALDI-TOF-TOF analysis was used to establish the protein identity. The
biological activity of purified protein was confirmed by the human
erythroleukemia TF-1 cell proliferation assay.
PMID- 27514668
TI - Structural manipulation and tailoring of dielectric properties in SrTi1-xFexTaxO3
perovskites: Design of new lead free relaxors.
AB - We report composition dependent structure evolution from SrTiO3 to SrFe0.5Ta0.5O3
by powder X-ray and neutron diffraction studies of SrTi1-2xFexTaxO3 (0.00 <= * <=
0.50) compositions. Structural studies reveal cubic (Pm3m) perovskite-type
structure of the parent SrTiO3 for x up to 0.075 and cation disordered
orthorhombic (Pbnm) perovskite-type structure for x >= 0.33. A biphasic region
consisting of a mixture of cubic and orthorhombic structures is found in the
range for 0.10 <= * <= 0.25. Dielectric studies reveal transformation from a
normal dielectric to relaxor like properties with increasing Fe(3+) and Ta(5+)
concentration. Dielectric response is maximum at x = 0.33 in the series. The
results establish a protocol for designing new lead-free relaxor materials based
on the co-substitution of Fe(3+) and Ta(5+) for Ti(4+) in SrTiO3. A complex
interplay of strain effects arising from distribution of cations at the
octahedral sites of the perovskite structure controls the dielectric properties.
PMID- 27514667
TI - Gastric biomarkers: a global review.
AB - BACKGROUND: Gastric cancer is an aggressive disease with a poor 5-year survival
and large global burden of disease. The disease is biologically and genetically
heterogeneous with a poorly understood carcinogenesis at the molecular level.
Despite the many prognostic, predictive, and therapeutic biomarkers investigated
to date, gastric cancer continues to be detected at an advanced stage with
resultant poor clinical outcomes. MAIN BODY: This is a global review of gastric
biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor
receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as
well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD
L1, TP53, and microsatellite instability. CONCLUSION: A deeper understanding of
the pathogenesis and biological features of gastric cancer, including the
identification and characterization of diagnostic, prognostic, predictive, and
therapeutic biomarkers, hopefully will provide improved clinical outcomes.
PMID- 27514670
TI - Halomonas lutescens sp. nov., a halophilic bacterium isolated from a lake
sediment.
AB - A novel, Gram-stain-negative, facultatively anaerobic, halophilic bacterium,
designated strain Q1UT, was isolated from a sediment sample collected from
Qinghai Lake, PR China. The cells of the strain were short rod-shaped (0.2
0.3*0.6-2.5 um) and non-motile. Strain Q1UT formed yellowish colonies and grew at
temperatures of 2-37 degrees C (optimum 30-33 degrees C), at pH 6.0-9.0
(optimum pH 7.0) and in the presence of 0-20 % (w/v) NaCl (optimum 7.5 %). The
major cellular fatty acids were C18 : 1omega7c (58.6 %), C16 : 1omega7c and/or
C16 : 1omega6c (14.8 %) and C16 : 0 (10.1 %). The polar lipids were identified as
diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unknown
phospholipid and unknown lipids. The genomic DNA G+C content was 61.5 mol%, and
the predominant respiratory ubiquinone Q-9. Based on phylogenetic analysis of the
16S rRNA gene sequences and concatenated 16S rRNA, gyrB and rpoD gene sequences,
the isolate was found to belong to the genus Halomonas in the class
Gammaproteobacteria. The most closely related species were Halomonas venusta DSM
4743T (98.3 % 16S rRNA sequence similarity), Halomonas songnenensis DSM 25870T
(98.2 %) and Halomonas hydrothermalis DSM 15725T (98.2 %). DNA-DNA relatedness
values between strain Q1UT and the type strains of eight other species of the
genus Halomonas ranged from 21.3 % to 10.1 %. On the basis of phenotypic,
phylogenetic and chemotaxonomic analyses, and DNA-DNA hybridization relatedness
values, strain Q1UT is considered to represent a novel species of the genus
Halomonas; the name Halomonas lutescens sp. nov. is proposed. The type strain is
Q1UT (=CGMCC 1.15122T=KCTC 42517T).
PMID- 27514669
TI - Mycobacterium tuberculosis H37Ra: a surrogate for the expression of conserved,
multimeric proteins of M.tb H37Rv.
AB - BACKGROUND: Obtaining sufficient quantities of recombinant M.tb proteins using
traditional approaches is often unsuccessful. Several enzymes of the glycolytic
cycle are known to be multifunctional, however relatively few enzymes from M.tb
H37Rv have been characterized in the context of their enzymatic and pleiotropic
roles. One of the primary reasons is the difficulty in obtaining sufficient
amounts of functionally active protein. RESULTS: In the current study, using M.tb
glyceraldehyde-3-phosphate dehydrogenase (GAPDH) we demonstrate that expression
in E. coli or M. smegmatis results in insolubility and improper subcellular
localization. In addition, expression of such conserved multisubunit proteins
poses the problem of heteromerization with host homologues. Importantly the
expression host dramatically affected the yield and functionality of GAPDH in
terms of both enzymatic activity and moonlighting function (transferrin binding).
The applicability of this system was further confirmed using two additional
enzymes i.e. M.tb Pyruvate kinase and Enolase. CONCLUSIONS: Our studies establish
that the attenuated strain M.tb H37Ra is a suitable host for the expression of
highly hydrophobic, conserved, multimeric proteins of M.tb H37Rv. Significantly,
this expression host overcomes the limitations of E. coli and M. smegmatis
expression and yields recombinant protein that is qualitatively superior to that
obtained by traditional methods. The current study highlights the fact that
protein functionality (which is an an essential requirement for all in vitro
assays and drug development) may be altered by the choice of expression host.
PMID- 27514671
TI - Imaging biomarkers for steatohepatitis and fibrosis detection in non-alcoholic
fatty liver disease.
AB - There is a need, in NAFLD management, to develop non-invasive methods to detect
steatohepatitis (NASH) and to predict advanced fibrosis stages. We evaluated a
tool based on optical analysis of liver magnetic resonance images (MRI) as
biomarkers for NASH and fibrosis detection by investigating patients with biopsy
proven NAFLD who underwent magnetic resonance (MR) protocols using 1.5T General
Electric (GE) or Philips devices. Two imaging biomarkers (NASHMRI and FibroMRI)
were developed, standardised and validated using area under the receiver
operating characteristic curve (AUROC) analysis. The results indicated NASHMRI
diagnostic accuracy for steatohepatitis detection was 0.83 (95% CI: 0.73-0.93)
and FibroMRI diagnostic accuracy for significant fibrosis determination was 0.85
(95% CI: 0.77-0.94). These findings were independent of the MR system used. We
conclude that optical analysis of MRI has high potential to define non-invasive
imaging biomarkers for the detection of steatohepatitis (NASHMRI) and the
prediction of significant fibrosis (FibroMRI) in NAFLD patients.
PMID- 27514672
TI - Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from
the human tumor-associated antigen Nectin-4.
AB - Nectin-4 is a tumor antigen present on the surface of breast, ovarian and lung
carcinoma cells. It is rarely present in normal adult tissues and is therefore a
candidate target for cancer immunotherapy. Here, we identified a Nectin-4
antigenic peptide that is naturally presented to T cells by HLA-A2 molecules. We
first screened the 502 nonamer peptides of Nectin-4 (510 amino acids) for binding
to and off-rate from eight different HLA class I molecules. We then combined
biochemical, cellular and algorithmic assays to select 5 Nectin-4 peptides that
bound to HLA-A*02:01 molecules. Cytolytic T lymphocytes were obtained from
healthy donors, that specifically lyzed HLA-A2(+) cells pulsed with 2 out of the
5 peptides, indicating the presence of anti-Nectin-4 CD8(+) T lymphocytes in the
human T cell repertoire. Finally, an HLA-A2-restricted cytolytic T cell clone
derived from a breast cancer patient recognized peptide Nectin-4145-153
(VLVPPLPSL) and lyzed HLA-A2(+) Nectin-4(+) breast carcinoma cells. These results
indicate that peptide Nectin-4145-153 is naturally processed for recognition by T
cells on HLA-A2 molecules. It could be used to monitor antitumor T cell responses
or to immunize breast cancer patients.
PMID- 27514675
TI - Analysis of relative kinematic index with normalized standing time between
subjects with and without recurrent low back pain.
AB - PURPOSE: Although subjects with recurrent low back pain (LBP) demonstrate altered
postural control, their postural steadiness during one leg standing is unknown.
The purpose of this study was to investigate postural steadiness based on
relative kinematic index of the lower limbs and trunk with normalized standing
time in subjects with recurrent LBP during dominant and non-dominant leg
standing. METHODS: Sixty individuals participated in the study, including 29
subjects in the control group (18 male, 11 female) and 31 subjects with recurrent
LBP (21 male, 10 female). The outcome measures included relative kinematic index
of the body regions and normalized standing time during the one leg standing
test. The relative kinematic index was the ratio between standstill time and
successful standing time. The normalized standing time was defined as a ratio
between the successful standing time and the requested standing time. RESULTS:
The control group demonstrated significantly longer normalized standing time on
the dominant (t = -2.57, p = 0.013) and non-dominant (t = -2.78, p = 0.007) legs
than the LBP group. The relative kinematic index of the core spine model
significantly decreased for the dominant (t = -3.01, p = 0.004) and non-dominant
(t = -3.06, p = 0.003) legs in the LBP group. In addition, the kinematic index
indicated pelvis and non-dominant shank during dominant leg standing (R 2 = 0.97)
in the LBP group. In the control group, the pelvis was significantly correlated
with the core spine model during standing on the dominant (R 2 = 0.95) and non
dominant (R 2 = 0.97) legs. CONCLUSIONS: The relative kinematic index of the
pelvis was found to be most significant for longer standing durations in both
groups. In the LBP group, the shank and foot were significantly higher in
addition to the pelvis due to possible compensatory motion. The control group
took advantage of pelvic control with the core spine to minimize lower limb
movements. Clinicians need to consider the core spine for pelvic control to
refine postural adaptations in subjects with recurrent LBP.
PMID- 27514677
TI - Quick Fire Presentations EUROSPINE 2016 Berlin, Germany, 5-7 October.
PMID- 27514674
TI - Who is distressed? A comparison of psychosocial stress in pregnancy across seven
ethnicities.
AB - BACKGROUND: Calgary, Alberta has the fourth highest immigrant population in
Canada and ethnic minorities comprise 28 % of its total population. Previous
studies have found correlations between minority status and poor pregnancy
outcomes. One explanation for this phenomenon is that minority status increases
the levels of stress experienced during pregnancy. The aim of the present study
was to identify specific types of maternal psychosocial stress experienced by
women of an ethnic minority (Asian, Arab, Other Asian, African, First Nations and
Latin American). METHODS: A secondary analysis of variables that may contribute
to maternal psychosocial stress was conducted using data from the All Our Babies
prospective pregnancy cohort (N = 3,552) where questionnaires were completed at <
24 weeks of gestation and between 34 and 36 weeks of gestation. Questionnaires
included standardized measures of perceived stress, anxiety, depression, physical
and emotional health, and social support. Socio-demographic data included
immigration status, language proficiency in English, ethnicity, age, and socio
economic status. RESULTS: Findings from this study indicate that women who
identify with an ethnic minority were more likely to report symptoms of
depression, anxiety, inadequate social support, and problems with emotional and
physical health during pregnancy than women who identified with the White
reference group. CONCLUSIONS: This study has identified that women of an ethic
minority experience greater psychosocial stress in pregnancy compared to the
White reference group.
PMID- 27514673
TI - Antigen Presentation After Stroke.
AB - Stroke induces a local inflammatory reaction and a plethora of innate immune
responses in the brain where antigen-presenting cells become prominent. However,
to date, it is still unclear whether antigen presentation is relevant to the
neuropathological and functional outcome of stroke. Stroke does not trigger overt
autoimmune reactions, but neural antigens have been found in lymphoid tissues of
patient with stroke and it is unknown whether they promote tolerance or immune
reactions that under certain conditions might contribute to the functional
worsening observed in some patients. Autoantibodies to neural molecules have also
been reported in patients with stroke, but the subclass of antibodies is
important for their function, and the contribution of such findings to stroke
outcome is not yet clear. Notably, stroke induces immunodepression highlighted by
a transient lymphopenia, lymphoid organ atrophy, and monocyte deactivation. While
these effects might reduce the chances of autoreactivity, they increase the risk
of infection in patients with stroke and most frequently in those with severe
stroke. Therefore any potential brain protective effect of stroke-induced
immunodepression by attenuating or preventing lymphocyte-mediated brain damage is
confounded by stroke severity and an increased incidence of infections. Systemic
inflammation due to a number of comorbidities that are frequent in patients with
stroke is also associated to a poor outcome. Herein, we review some relevant
findings regarding the identification of neural antigens in stroke and discuss
their potential contribution to the functional outcome of stroke.
PMID- 27514678
TI - Oral Presentations EUROSPINE 2016 Berlin, Germany, 5-7 October.
PMID- 27514676
TI - The effects of the three-dimensional deformity of adolescent idiopathic scoliosis
on pulmonary function.
AB - PURPOSE: Utilizing 2D measurements, previous studies have found that in AIS,
increased thoracic Cobb and decreased thoracic kyphosis contribute to pulmonary
dysfunction. Recent technology has improved our ability to measure and understand
the true 3D deformity in AIS. The purpose of this study was to evaluate which 3D
radiographic measures predict pulmonary dysfunction. METHODS: One hundred and
sixty-three surgically treated AIS patients with preoperative PFTs (FEV, FVC,
TLC) and EOS(r) imaging were identified at a single center. Each spine was
reconstructed in 3D to obtain the true coronal, sagittal, and apical rotational
deformities. These were then correlated with the patient's preoperative PFT
measurements. Regression analysis was performed to determine the relative effect
of each radiographic measure. RESULTS: There were 124 thoracic and 39 lumbar
major curves. The range of preoperative thoracic and lumbar 3D coronal angle was
11-115 degrees and 11-98 degrees , respectively. The range of preoperative
thoracic 3D kyphosis (T5-T12) and thoracic apical vertebral rotation was -56 to
44 degrees and 0-29 degrees , respectively. Increasing thoracic 3D Cobb and
thoracic vertebral rotation and decreasing thoracic 3D kyphosis most
significantly correlated with decreasing pulmonary function, especially FEV. In
patients with the largest degree of thoracic deformity (3D Coronal Cobb > 80
degrees , 3D thoracic lordosis >20 degrees , and absolute apical rotation >25
degrees ), the majority of patients had moderate to severe pulmonary impairment
(<=65 % predicted). 3D thoracic kyphosis was the most consistent predictor of FEV
(r 2 = 0.087), FVC (r 2 = 0.069), and TLC (r 2 = 0.098) impairment. CONCLUSIONS:
Larger thoracic coronal, sagittal, and axial deformities increase the risk of
pulmonary impairment in patients with AIS. Of these, decreasing 3D thoracic
kyphosis is the most consistent predictor. This information can guide surgeons in
the decision making process for determining which surgical techniques to utilize
and which component of the deformity to focus on.
PMID- 27514679
TI - Posters Presentations EUROSPINE 2016 Berlin, Germany, 5-7 October.
PMID- 27514681
TI - Oral Presentations EUROSPINE Spring Speciality Meeting, 12-13 May 2016 Krakow,
Poland.
PMID- 27514680
TI - Index: Abstracts EUROSPINE 2016 Berlin, Germany, 5-7 October.
PMID- 27514682
TI - Quick Fire Presentations EUROSPINE Spring Speciality Meeting, 12-13 May 2016,
Krakow, Poland.
PMID- 27514683
TI - Announcements for issue 9, 2016.
PMID- 27514684
TI - Index for EUROSPINE Spring Speciality Meeting, 12-13 May, Krakow, Poland.
PMID- 27514685
TI - Adaptation and acclimation of traits associated with swimming capacity in Lake
Whitefish (coregonus clupeaformis) ecotypes.
AB - BACKGROUND: Improved performance in a given ecological niche can occur through
local adaptation, phenotypic plasticity, or a combination of these mechanisms.
Evaluating the relative importance of these two mechanisms is needed to better
understand the cause of intra specific polymorphism. In this study, we reared
populations of Lake Whitefish (Coregonus clupeaformis) representing the'normal'
(benthic form) and the 'dwarf' (derived limnetic form) ecotypes in two different
conditions (control and swim-training) to test the relative importance of
adaptation and acclimation in the differentiation of traits related to swimming
capacity. The dwarf whitefish is a more active swimmer than the normal ecotype,
and also has a higher capacity for aerobic energy production in the swimming
musculature. We hypothesized that dwarf fish would show changes in morphological
and physiological traits consistent with reductions in the energetic costs of
swimming and maintenance metabolism. RESULTS: We found differences in traits
predicted to decrease the costs of prolonged swimming and standard metabolic rate
and allow for a more active lifestyle in dwarf whitefish. Dwarf whitefish evolved
a more streamlined body shape, predicted to lead to a decreased drag, and a
smaller brain, which may decrease their standard metabolic rate. Contrary to
predictions, we also found evidence of acclimation in liver size and metabolic
enzyme activities. CONCLUSION: Results support the view that local adaptation has
contributed to the genetically-based divergence of traits associated with
swimming activity. Presence of post-zygotic barriers limiting gene flow between
these ecotype pairs may have favoured repeated local adaptation to the limnetic
niches.
PMID- 27514686
TI - Elemental Composition of Plant Species from an Abandoned Tungsten Mining Area:
Are They Useful for Biogeochemical Exploration and/or Phytoremediation Purposes?
AB - We aimed to evaluate the elemental (W, Mo, Zn, Fe, Cu, Co, Bi, Mn, Cd, Cr, As)
composition of some plant species spread around the abandoned tungsten mining
area of Uludag Mountain. The plant species tested were Anthemis cretica and
Trisetum flavescens which are grown in this area and they are pioneer species on
these contaminated sites. W levels in soils were found up to 1378.6 +/- 672.3
mg/kg dry weight in contaminated areas. The leaf W contents of the selected plant
species were found 41.1 +/- 24.4 and 31.1 +/- 15.5 mg/kg dry weight for A.
cretica and T. flavescens, respectively. Our results indicate that the elemental
composition of species changed by the increased tungsten and some element
concentrations in soil without detrimental effect. So, these species can be
useful tungsten removal and some elements from contaminated sites.
PMID- 27514689
TI - Misdiagnosis of cerebral malaria initially as acute psychotic disorder and later
as human rabies: a case report.
AB - BACKGROUND: Cerebral malaria is arguably one of the most common non-traumatic
encephalopathies in the developing world. Unless the diagnosis of cerebral
malaria is made promptly, the consequence could be disastrous. Even though the
diagnosis of cerebral malaria can be made relatively easily in majority of cases
atypical presentation can often lead to misdiagnosis or delayed diagnosis. We
report a case of an uncommon presentation of Plasmodium falciparum infection in a
17-year-old school girl with altered sensorium, seizures and phobic spasms. CASE
PRESENTATION: A previously healthy 17-year-old school girl was admitted to our
hospital with acute condition characterised by comatose state, recurrent seizures
and phobic spasms. She initially presented to a local hospital with agitation and
over talkativeness and was diagnosed as having an acute psychotic state. Few days
later she became drowsy and developed recurrent seizures and marked phobic spasms
which prompted the treating physician to diagnose human rabies. However, further
investigations carried out in our unit (including rapid antigenic test for P.
falciparum and peripheral blood smear) were positive for P. falciparum. She was
treated as for cerebral malaria with intravenous quinine and discharge from
hospital with no residual neurological deficit. CONCLUSION: Atypical presentation
of cerebral malaria can often lead to misdiagnosis. This patient presented with
encephalopathic illness with phobic spasms was initially misdiagnosed as human
rabies. Therefore, the physicians in malarial endemic areas should be vigilant of
similar presentations and should consider cerebral malaria as a possibility.
PMID- 27514688
TI - Treatment-seeking behaviour for childhood fever among caretakers of Chivuna and
Magoye rural communities of Mazabuka District, Zambia: a longitudinal study.
AB - BACKGROUND: Treatment-seeking for childhood fever among caretakers in most rural
parts of African region is still a major challenge. The aim of this study was to
determine the treatment seeking behaviour for fever in under-5 children of Magoye
and Chivuna rural areas of Mazabuka district in Zambia. METHODS: Treatment
seeking behaviour was explored longitudinally among caretakers of 362 children
aged 12-59 months with fever. The data was collected from caretakers using a
structured interviewer-administered questionnaire at their homes. Chi-square
test, one-sample test of proportions and logistic regression were the statistical
methods used for data analysis. RESULTS: Of the 362 children with fever, 77 % of
them had their treatment sought externally. In which 64 % had their treatment at
health facility (HF), 18 % from community health workers (CHW), and 18 % from
other sources. Early treatment (<= 24 h) was sought for 42 % of the fever
episodes. In dry season, a child had 1.53 times more likely to have early
treatment compared to rainy season [OR 1.53; 95 % CI 1.30, 1.80; p < 0.001]. A
child in Chivuna was less likely to have early treatment compared to one in
Magoye [OR 0.62; 95 % CI 0.50, 0.76; p < 0.001]. Caretakers had a reduced chance
of 27 % [OR 0.73; 95 % CI 0.56, 0.95; p = 0.022] of seeking early treatment if
they took a child to other sources compared to a HF. CONCLUSION: This study has
revealed that seeking early and appropriate treatment was suboptimal in the study
areas. Source of treatment, season and location were predictors of early
treatment of fever among caretakers. Policies aimed at combating poor care
seeking behaviour should not omit to address these factors.
PMID- 27514687
TI - Heregulin-1beta and HER3 in hepatocellular carcinoma: status and regulation by
insulin.
AB - BACKGROUND: The heregulin-1beta/HER3-driven pathway is implicated in several
epithelial malignancies and its blockade is currently undergoing clinical
investigation. Paradoxically, the status and the regulation of this pathway is
poorly known in hepatocellular carcinoma (HCC). METHODS: Using 85 HCC obtained
after tumour resection, heregulin-1beta and HER3 expression was evaluated by real
time RT-PCR, ELISA and/or immunohistochemistry. Statistics were performed to
analyze associations between gene expression and clinicopathological parameters.
The effects of insulin on the heregulin-1beta/HER3 pathway was investigated in
four HCC cell lines. RESULTS: HER3 mRNA was upregulated in 52 % of tumours, while
heregulin-1beta mRNA was downregulated in 82 %. Hepatitis B and C viral
infections were respectively associated with high and low HER3 mRNA expression.
No association was seen between neither HER3 or heregulin-1beta mRNA and
prognostic factors, survival or recurrence. Immunohistochemistry showed
predominant cytoplasmic staining of HER3 in tumours but the staining was
nonreproducible. HER3 mRNA and protein levels were not correlated in liver
tissues. In HCC cells, insulin promoted HER3 proteasomal degradation and
inhibited heregulin-1beta stimulation of cell migration. HER3 and insulin
receptor co-immunoprecipitated in these cells. The loss of insulin receptor
expression by RNA interference sensitized cells to heregulin-1beta-induced AKT
phosphorylation. CONCLUSIONS: Autocrine heregulin-1beta loop is uncommon in HCC
and HER3 mRNA expression is differentially influenced by hepatitis viruses.
Insulin is a negative regulator of HER3 protein expression and function in HCC
cells. Altogether these data may explain why HER3 and heregulin-1beta expression
have no prognostic value and suggest that HCC patients are unlikely to derive
benefit from HER3-targeted monotherapies.
PMID- 27514690
TI - Use of laboratory and administrative data to understand the potential impact of
human parainfluenza virus 4 on cases of bronchiolitis, croup, and pneumonia in
Alberta, Canada.
AB - BACKGROUND: Human Parainfluenza Virus (hPIV) causes severe respiratory illness in
infants and adults. Our study describes the association of hPIV1-4 with
bronchiolitis, croup, and pneumonia using retrospective laboratory,
administrative and public health data. Due to issues including the historic lack
of hPIV4 in some commercial respiratory virus panels, the description of the
impact of hPIV4 on croup, bronchiolitis, and pneumonia at population levels has
often been limited. This study will use routine clinical laboratory data, and
administrative data to provide a preliminary description of the impact of hPIV4
on these diseases in our population. METHODS: A three year cohort of patients
positive for hPIV was linked with data from physician visits and hospital
admissions to define cases and hospitalization status. International
Classification of Disease (ICD-9) codes were used to determine if cases had
croup, bronchiolitis, and pneumonia. We also looked at differences in
hospitalization status, age and gender among hPIV1-4. All statistical analysis
was done using SPSS (Version 19.0.0, IBM Corp(c) 2010) and Graphpad Prism V6
(GraphPad Software, Inc., 2012). RESULTS: Only hPIV1 and hPIV4 specimens had
positivity rates greater than 5 % of all specimens sent for respiratory virus
panel testing. hPIV1 exhibited a biennial pattern while the pattern for hPIV3 was
less interpretable due to lower positivity rates. Circulation patterns for hPIV2
and hPIV4 were not assessed due to the low positivity rates of theses specimens.
From 2010 to 2013, there were 2300 hPIV cases with hPIV3 (46 %) being the most
common, followed by hPIV1 (27 %), hPIV4 (16 %) and hPIV2 (11 %). The median age
was 2 years for all hPIV types. Males were slightly greater than females for
hPIV1 and hPIV2, with an equal distribution for hPIV3 and slightly more females
than males for hPIV4. hPIV1 and hPIV2 had the highest or proportion of croup
while hPIV3 and hPIV4 had the highest proportion of pneumonia. Within hPIV4
cases, distributions of diseases were; pneumonia (21 %, 95 % CI 17.1-25.7),
bronchiolitis (18 %, 95 % CI 14.3-22.5), croup (2 %, 95 % CI 0.8-3.9), mixed
illness of any of pneumonia, bronchiolitis or croup (4 %, 95 % CI 2.5-7.0) or
other respiratory diseases (54 %, 95 % CI 49.1-59.6). CONCLUSIONS: We used
laboratory and administrative data to undertake a descriptive analysis of the
association of hPIV1-4 with croup, bronchiolitis and pneumonia. hPIV4 appears to
be more associated more with bronchiolitis and pneumonia and less with croup in
our population.
PMID- 27514691
TI - Examination of the Phenomenology and Clinical Correlates of Emetophobia in a
Sample of Salvadorian Youths.
AB - Emetophobia is an under-researched disorder characterized by a specific fear of
vomiting. There is a paucity of research on this impairing condition, with extant
examinations being largely limited to adult samples and online communities. The
present study examined the incidence, phenomenology, and correlates of
emetophobia in 305 Salvadorian youths. Caregivers completed a battery of
questionnaires regarding the youth's symptoms of emetophobia,
internalizing/externalizing symptoms, health anxiety, and obsessive-compulsive
symptoms. Approximately 7.5 % of the sample was elevated on emetophobia symptoms,
and higher levels of emetophobia symptoms were correlated with higher levels of
internalizing, externalizing, health anxiety, and obsessive-compulsive symptoms,
and lower levels of adaptive functioning. Youths meeting the cutoff for elevated
emetophobia symptoms versus those who did not demonstrated significantly higher
levels of externalizing behaviors, as well as general obsessive-compulsive
symptoms, especially doubting/checking and neutralizing behaviors. These findings
are hoped to help improve the conceptualization and treatment of this poorly
understood disorder.
PMID- 27514692
TI - Separation behavior of basic compounds on unbonded silicon oxynitride and silica
high-performance liquid chromatography stationary phases with reversed-phase
eluents.
AB - Unbonded silicon oxynitride and silica high-performance liquid chromatography
stationary phases have been evaluated and compared for the separation of basic
compounds of differing molecular weight, pKa , and log D using aqueous/organic
mobile phases. The influences of percentage of organic modifier, buffer pH, and
concentration in the mobile phase on base retention were investigated on unbonded
silicon oxynitride and silica phases. The results confirmed that unbonded silicon
oxynitride and silica phases demonstrated excellent separation performance for
model basic compounds and both the unbonded phases examined possessed a
hydrophobic/adsorption and ion-exchange character. The silicon oxynitride
stationary phase exhibited high hydrophilicity compared with silica with a
reversed-phase mobile phase. An ion-exclusion-type mechanism becomes predominant
for the separation of three aimed bases on the silicon oxynitride column at pH
2.8. Different from silicon oxynitride stationary phase, no obvious change for
the retention time of three model bases on silica stationary phase at pH 2.8 can
be observed.
PMID- 27514693
TI - Factors associated with choosing the emergency department as the primary access
point to health care: a Canadian population cross-sectional study.
AB - OBJECTIVE: Approximately 4.3 million Canadians are without a primary care
physician, of which 13% choose the emergency department (ED) as their regular
access point to health care. We sought to identify factors associated with
preferential ED use over other health services. We hypothesized that
socioeconomic barriers (i.e., employment, health status, education) to primary
care would also prevent access to ED alternatives. METHODS: Data from the
Canadian Community Health Survey, 2007 to 2008, were analysed (N=134,073;
response rate 93.5%). Our study population comprised 14,091 individuals
identified without a primary care physician. Socioeconomic variables included
employment, health, and education. Covariates included chronic health conditions,
immigrant status, gender, age, and mental health. Prevalence estimates and 95%
confidence intervals (CIs) for each variable were calculated. Weighted logistic
regression models were constructed to evaluate the importance of individual risk
factors and their interactions after adjustment for relevant covariates. RESULTS:
The sample comprised 57.2% males from across Canada. Employment (OR 0.73 [95% CI:
0.59-0.90]), good health (OR 0.73 [95% CI 0.57-0.88]), and post-secondary
education (OR 0.68 [95% CI 0.53-0.88]) reduced respondents use of the ED. The
reduced odds of ED use were independent of chronic conditions, mental health,
gender, poor mobility, province, and age. CONCLUSIONS: Low socioeconomic status
dictates preferential ED use in those without a primary care physician. Specific
policy and system development targeting this at-risk population are indicated to
alter ED use patterns in this population.
PMID- 27514694
TI - Effects of Organogel Hardness and Formulation on Acceptance of Frankfurters.
AB - Different organogel formulations used as beef fat (BF) replacement (0%, 20%, 40%,
60%, and 80%) were utilized to optimize the mechanical properties of
frankfurters. Organogels, made of canola oil (CO), included different
concentrations of ethyl cellulose (EC) and sorbitan monostearate (SMS). They
consisted of: 8% EC + 1.5% SMS referred to as organogel-I (OG-I), 8% EC + 3.0%
SMS (OG-II), and 10% EC + 1.5% SMS (OG-III), which were found promising in a
previous study when used at 100% replacement. Replacement of BF with organogels
at all levels could bring down the very high hardness values (texture profile
analysis and sensory) of frankfurters prepared using CO by itself, relative to
the BF control. OG-I and OG-II quantity had no significant effect on hardness and
springiness, being similar in many cases to the BF and lower than the CO control.
Shear force values of all organogel treatments were not significantly different
from one another, and were between the BF and CO controls. Smokehouse yield
showed a pattern of decreasing losses with increasing organogel replacement
level. Sensory analysis revealed that using CO by itself significantly increased
hardness, but structuring the oil (via organogelation), brought it down to the BF
control value in all OG-I and OG-II formulations. Juiciness was significantly
reduced by using liquid oil but increased with raising the amount of organogels.
Oiliness sensation increased with higher organogel substitution and was actually
higher than the beef control. The study demonstrates the potential use of
vegetable oil structuring in replacing the more saturated BF in emulsion-type
meat products.
PMID- 27514695
TI - Intermediate stages of electrochemical oxidation of single-crystalline platinum
revealed by in situ Raman spectroscopy.
AB - Understanding the atomistic details of how platinum surfaces are oxidized under
electrochemical conditions is of importance for many electrochemical devices such
as fuel cells and electrolysers. Here we use in situ shell-isolated nanoparticle
enhanced Raman spectroscopy to identify the intermediate stages of the
electrochemical oxidation of Pt(111) and Pt(100) single crystals in perchloric
acid. Density functional theory calculations were carried out to assist in
assigning the experimental Raman bands by simulating the vibrational frequencies
of possible intermediates and products. The perchlorate anion is suggested to
interact with hydroxyl phase formed on the surface. Peroxo-like and superoxo-like
two-dimensional (2D) surface oxides and amorphous 3D alpha-PtO2 are sequentially
formed during the anodic polarization. Our measurements elucidate the process of
the electrochemical oxidation of platinum single crystals by providing evidence
for the structure-sensitive formation of a 2D platinum-(su)peroxide phase. These
results may contribute towards a fundamental understanding of the mechanism of
degradation of platinum electrocatalysts.
PMID- 27514696
TI - Evaluation of Interspinous Spacer Outcomes in Degenerative Lumbar Canal Stenosis:
Clinical Study.
AB - BACKGROUND: Lumbar spinal stenosis is a common diagnosis in elderly individuals,
and the rates of surgery have risen all over the world. The optimal approach to
provide satisfactory decompression and minimize complications for lumbar spinal
stenosis remains controversial. OBJECTIVE: The purpose of this study was to
evaluate the surgical outcome of interspinous spacers versus decompressive
laminectomy in the management of degenerative lumbar canal stenosis. PATIENTS AND
METHODS: Our prospective, comparative study included 2 groups of patients who
were operated on in Ain Shams University Hospitals between January 2010 and
December 2014. In the first group, 28 patients underwent decompression and
additional implantation of an interspinous spacer (ISP). In the second group, 25
patients underwent decompressive laminectomy (DL). RESULTS: Our statistical
results revealed no significant difference in outcome between the 2 groups
regarding visual analog scale score for leg pain and Oswestry Low Back Pain
Disability Index. However, the improvement (visual analog scale score) for back
pain was better in the DL group. Complication and reoperation rates were higher
in the ISP group. CONCLUSION: Although decompression and additional implantation
of an ISP are safe procedures, they do not show better improvement in clinical
outcome as compared with decompressive laminectomy.
PMID- 27514697
TI - Redefining Congenital Atlantoaxial Dislocation: Objective Assessment in Each
Plane Before and After Operation.
AB - BACKGROUND: The C1-C2 joint has multiple degrees of freedom of movement and C1-C2
dislocation (AAD) is often multiplanar. The existing methodology to assess the
dislocation is limited to few planes. The object of this study is to redefine and
objectively assess congenital AAD in each possible plane, before and after the
operation. METHODS: This study consisted of 95 patients of irreducible congenital
AAD operated on with the posterior approach alone. Preoperative and postoperative
computed tomography imaging was studied in the axial, coronal, and sagittal
planes. The relationship of C1-C2 along with the C1-C2 joint inclination was
studied in each plane. The extent and type of dislocation was objectively
assessed in each plane (newer indices) and compared with follow-up imaging for
correction. The preoperative and postoperative Japenese orthopaedics association
scores were compared. RESULTS: The commonest variety (61 patients) was a
combination of anteroposterior (AP) and vertical C1-C2 dislocation. Five patients
had predominant APnteroposterior, 6 vertical, 4 axial rotational, 9 lateral
angular tilt, and 3 had lateral transalational. Seven patients had a combination
of dislocation in AP, vertical, and rotational planes. AP dislocation was seen
with sagittal inclination of C1-C2 joints and vertical dislocation with coronal
inclination. Asymmetry in the joint's sagittal inclination added to a rotational
component, whereas asymmetry in the coronal angulation caused lateral angular
tilt. Pure rotational or lateral translation dislocation had near-normal C1-C2
orientation. Preoperative Japenese orthopaedics association score was worst in
the lateral tilt and the lateral translation. Correction in all planes was
achieved in all patients. CONCLUSIONS: The objective assessment of C1-C2
dislocation and joints in each plane was to determine its management and help in
achieving multiplanar correction.
PMID- 27514698
TI - The DERIVO Embolization Device in the Treatment of Intracranial Aneurysms: Short-
and Midterm Results.
AB - OBJECTIVE: The DERIVO embolization device (DED) is a new nitinol flow diverter
stent manufactured for the treatment of intracranial aneurysms. In this study, we
evaluated the safety and efficacy of the DED in the treatment of intracranial
aneurysms and present the short- and midterm results. METHODS: We treated 34
aneurysms using 26 devices in 24 patients with wide-necked, mostly medium-sized,
and fusiform aneurysms. Fourteen of the patients included in the study were women
and the other 10 were men. Headache was the most frequent symptom. Although 31
(91.2%) aneurysms were in the anterior circulation, 3 (8.8%) were in the
posterior. Intracranial stent medication was accomplished in all patients. All
patients were evaluated 1 day later for any ischemic lesion with diffusion
weighted imaging. The first and second follow-up angiograms were planned to be
performed after 3 and 9 months. RESULTS: In all patients, the treatment was
successful. No hemorrhagic complication was seen on computed tomography scan
performed immediately after the procedure. All patients were discharged without
any neurologic deficit. Although 20 (71.4%) of 28 aneurysms in 20 patients were
totally closed on the 3-month follow-up angiogram, 14 (77.8%) of 18 aneurysms in
9 patients were totally closed on the 9-month follow-up. General morbidity was
8.4%, and mortality was 4.3%. CONCLUSIONS: The DED seems effective and safe in
the treatment of different kinds of intracranial aneurysms.
PMID- 27514699
TI - En Route to Stimuli-Responsive Boron-, Nitrogen-, and Sulfur-Doped Polycyclic
Aromatic Hydrocarbons.
AB - Replacing both meso carbon atoms of the polycyclic aromatic hydrocarbon (PAH)
bisanthene by boron atoms creates an efficient blue fluorophore with a strong
electron-accepting character. The corresponding meso-B,S-doped bisanthene
exhibits a solvent-dependent green-to-orange photoluminescence and undergoes a
reversible reduction at E1/2 =-2.06 V (vs. FcH/FcH(+) ). After oxidation of the
sulfur atom, the resulting sulfoxide emits in the blue range of the spectrum,
shows only negligible solvatochromism, and a reversible redox transition at E1/2
=-1.74 V. Several related B, N- and B, S-containing PAHs have been prepared
following the same modular synthetic procedure and are also described herein. In
order to systematically compare their optoelectronic properties, all products
have been investigated by cyclic voltammetry as well as UV/Vis
absorption/emission spectroscopy.
PMID- 27514701
TI - Closing the gap: astrocytes and brain metastasis.
AB - Astrocytes are emerging as essential regulators of brain metastasis progression.
In a current issue of Nature, Chen et al. identify a novel mechanism of astrocyte
carcinoma interaction and exploit vulnerabilities therein to slow brain
metastatic growth in pre-clinical models.
PMID- 27514700
TI - Ferroptosis is an autophagic cell death process.
AB - Ferroptosis is an iron-dependent form of regulated necrosis. It is implicated in
various human diseases, including ischemic organ damage and cancer. Here, we
report the crucial role of autophagy, particularly autophagic degradation of
cellular iron storage proteins (a process known as ferritinophagy), in
ferroptosis. Using RNAi screening coupled with subsequent genetic analysis, we
identified multiple autophagy-related genes as positive regulators of
ferroptosis. Ferroptosis induction led to autophagy activation and consequent
degradation of ferritin and ferritinophagy cargo receptor NCOA4. Consistently,
inhibition of ferritinophagy by blockage of autophagy or knockdown of NCOA4
abrogated the accumulation of ferroptosis-associated cellular labile iron and
reactive oxygen species, as well as eventual ferroptotic cell death. Therefore,
ferroptosis is an autophagic cell death process, and NCOA4-mediated
ferritinophagy supports ferroptosis by controlling cellular iron homeostasis.
PMID- 27514702
TI - Mitochondrial fusion fuels T cell memory.
AB - Differences in mitochondrial structures determine the metabolic landscape of
effector and memory T cell populations in vivo.
PMID- 27514703
TI - Endoscopic biodegradable biliary stents in the treatment of benign biliary
strictures: First report of clinical use in patients.
AB - The first clinical experience of endoscopically inserted polydioxanone
biodegradable biliary stents (BDBS) in the treatment of benign biliary strictures
is reported. Two patients with a benign common bile duct stricture were
endoscopically treated with 8-mm-bore BDBS during endoscopic retrograde
cholangiography. Both BDBS insertions were technically successful and without
adverse events. At 6 months, the stricture resolution was excellent and BDBS
degradation was predicted in repeated magnetic resonance imaging. The first
experience with endoscopic BDBS seems promising in the treatment of benign
biliary strictures. During 6 months of follow up, BDBS seemed sufficient for
remodeling and resolution of strictures. Further studies are needed to confirm
the effectiveness of biodegradable biliary stents in endoscopic management of
benign biliary strictures.
PMID- 27514704
TI - Bioactive lipids accumulate in stored red blood cells despite leukoreduction: a
targeted metabolomics study.
AB - BACKGROUND: Accumulation of bioactive lipids during red blood cell (RBC) storage
has been identified as a potential source of posttransfusion sequelae in
vulnerable populations. Typically, white blood cells (WBCs) have been implicated
in the generation of bioactive lipids, and leukoreduction has been seen as a
solution to this issue. STUDY DESIGN AND METHODS: We developed a targeted
metabolomics approach with isotope dilution to quantify a panel of bioactive
lipids in both leukoreduced (LR) and nonleukoreduced (NLR) RBC units over the
course of storage. RESULTS: Leukoreduction greatly attenuated the production of
12-hydroxyeicosatetraenoic acid (HETE), 12-hydroxyeicosapentaenoic acid, and 14
hydroxydocosahexaenoic acid (HDoHE), all three of which are mediated by 12
lipoxygenase present in WBCs and platelets. However, despite leukoreduction,
micromolar levels of linoleic acid (LA), arachidonic acid (AA), and
docosahexaenoic acid (DHA) were observed in the RBC units stored for 42 days.
These major polyunsaturated fatty acids (PUFAs) and their oxidation products
(oxylipins) also significantly increased with storage time, including 5-, 8-, 9-,
11-, 12-, and 15- HETEs from AA; 9- and 13-hydroxyoctadecadienoic acid (HODE); 9
, 10-, and 12,13-dihydroxyoctadecenoic acids from LA; and 14-, 16-, and 17-HDoHEs
from DHA. The majority of PUFAs and oxylipins accumulated in the supernatant
fraction. Large donor-to-donor variations were observed in both LR-RBC and NLR
RBC units. CONCLUSION: While the exact role the accumulation of PUFAs and
oxylipins plays in RBC unit quality and transfusion medical outcomes remains
undetermined, the analytes of interest in this study may serve as biomarkers for
lipid degradation and oxidation during storage and may induce changes in human
physiology upon transfusion.
PMID- 27514705
TI - Roadmap for improving patient and graft survival in the next 10 years.
PMID- 27514706
TI - Adnexal tumor of probable Wolffian origin arising from retroperitoneal space.
PMID- 27514707
TI - ABC Transporters and Drug Resistance in Patients with Epilepsy.
AB - Resistance to antiepileptic drugs (AED) remains a major problem in clinical
epileptology. This pharmacoresistance is independent of the choice of AEDs.
Different hypotheses have been proposed to explain the neurobiological basis for
pharmacoresistance in epilepsy. The transporter hypothesis is the mostly
investigated theory. Hereby, overexpression of multidrug efflux transporters,
such as P-glycoprotein (Pgp), at the blood-brain-barrier (BBB) is thought to be
involved in pharmacoresistance in epilepsy by extruding AEDs from their target
site. Accumulating evidence supports an overexpression of Pgp in
pharmacoresistant epilepsy. Molecular Imaging studies provide unique
opportunities for the in-vivo study of the transporter hypothesis in the central
nervous system (CNS). Several studies demonstrated that positron emission
tomography (PET) with [11C]-radiolabled Pgp substrates is a promising tool for in
vivo investigation of Pgp function at the rat, monkey and human BBB.
Quantification of Pgp over activity in epilepsy patients by in vivo imaging could
be highly useful because altered treatment strategies or novel AED could then be
applied.
PMID- 27514708
TI - In Vitro and Ex Vivo Model Systems to Measure ABC Transporter Activity at the
Blood-Brain Barrier.
AB - With the aging population the occurrence of central nervous system diseases such
as cancer, mental disorders and neurodegenerative diseases, is expected to
increase and hence, the demand for effective drugs. However, the passage of drugs
across the blood-brain barrier represents a major challenge in accomplishing
efficient brain delivery of therapeutic agents. This highly efficient barrier is
composed of a monolayer of capillary endothelial cells supported by pericytes and
astrocytic end-feet, that together effectively shield the brain from the blood.
The brain microvascular endothelial cells form a physical and metabolic barrier
where paracellular and transcellular transport of molecules in and out of the
brain is closely regulated, allowing nutrients to pass but preventing the entry
of harmful neurotoxic substances, including drugs. For this purpose brain
endothelial cells express efficient efflux pumps, such as ATP binding cassette
(ABC) transporters, which limit the delivery of drugs into the brain. To treat
the above-mentioned chronic central nervous system disorders, it is crucial to
design compounds that can pass the blood-brain barrier and thus the ABC
transporters. In order to achieve this, representative models of the blood-brain
barrier with predictive validity are necessary. This review discusses the current
in vitro and ex vivo model systems that are used to measure ABC transporter
activity in order to study potential in vivo efficacy of blood-brain barrier-drug
passage.
PMID- 27514709
TI - Adolescent Cannabis Use: What is the Evidence for Functional Brain Alteration?
AB - BACKGROUND: Cannabis use typically commences during adolescence, a period during
which the brain undergoes profound remodeling in areas that are high in
cannabinoid receptors and that mediate cognitive control and emotion regulation.
It is therefore important to determine the impact of adolescent cannabis use on
brain function. OBJECTIVE: We investigate the impact of adolescent cannabis use
on brain function by reviewing the functional magnetic resonance imaging studies
in adolescent samples. METHOD: We systematically reviewed the literature and
identified 13 functional neuroimaging studies in adolescent cannabis users (aged
13 to 18 years) performing working memory, inhibition and reward processing
tasks. RESULTS: The majority of the studies found altered brain function, but
intact behavioural task performance in adolescent cannabis users versus controls.
The most consistently reported differences were in the frontal-parietal network,
which mediates cognitive control. Heavier use was associated with abnormal brain
function in most samples. A minority of studies controlled for the influence of
confounders that can also undermine brain function, such as tobacco and alcohol
use, psychopathology symptoms, family history of psychiatric disorders and
substance use. CONCLUSION: Emerging evidence shows abnormal frontal-parietal
network activity in adolescent cannabis users, particularly in heavier users.
Brain functional alterations may reflect a compensatory neural mechanism that
enables normal behavioural performance. It remains unclear if cannabis exposure
drives these alterations, as substance use and mental health confounders have not
been systematically examined.
PMID- 27514710
TI - Importance of ABC Transporters in Drug Development.
AB - ATP-binding cassette (ABC) transporters are a huge family of ATP-dependent
transmembrane proteins whose main function is exporting or importing substances
or molecules through the cell membranes, plasma cell membrane, or inner membranes
in organelles. They fulfill these functions by maintaining cell integrity,
metabolism, and homeostasis. They are expressed in a variety of tissues as they
transport numerous essential compounds including lipids and other signaling
molecules. ABC transporters became widely studied since the discovery of their
ability to carry a multitude of xenobiotics, including therapeutic drugs, and in
light of the fact that they represent a hurdle for the treatment of resistant
cancers. In contrast, the role of ABC transporters in neurological diseases like
Alzheimer's and Parkinson's, depression, schizophrenia, and epilepsy remains
controversial and their mechanism of action in these pathologies remains elusive,
thus hindering the implementation of therapies aimed at modulating the functions
of these transporters. To date, a number of natural and synthetic compounds are
known to act as inhibitors, substrates, and even inducers of these transporters,
being able to modulate their expression and/or function; however, their
implication as therapeutic agents is far from reaching wide clinical utilization.
This review highlights the importance of overcoming the challenges posed by ABC
transporters in drug development.
PMID- 27514711
TI - Design and Synthesis of New Selective P-gp Substrates and Inhibitors.
AB - P-glycoprotein is an ATP-binding cassette transporter involved in drug
absorption, distribution and excretion. It pumps a wide range of xenobiotic
compounds out of the cells and plays a crucial role in Multi Drug Resistance.
Moreover, recent studies have demonstrated that changes in P-gp function and/or
expression at the blood brain barrier are implicated in the pathogenesis of
neurological disorders such as therapy-refractory epilepsy, Alzheimer's and
Parkinson's disease. In the last decades the studies have been addressed to the
discovery of potent P-gp inhibitors able to revert pharmacoresistance and to the
development of PET tracers to detect P-gp activity and expression for an early
diagnosis and therapy monitoring of neurodegenerative disease. However, clinical
trials have reported only limited success in reversing MDR and radiolabeled
ligands were not actually useful to study differences of transporter function in
different brain regions due to their low brain uptake. The difficulties into the
discovery of new ligands is due to the use of different experimental assays, to
the fact that P-gp is highly flexible protein with different binging sites and
available crystallographic structures for the protein have inadequate resolution.
To overcome these limitations research groups prefer computational approaches
such as homology models in their structure-based design or ligand-based
methodologies. A recent approach aimed to identify ligands which can interrupt
ATP-binding and hydrolysis by P-gp, by interacting at the NBDs of the protein. In
this review results from radiolabeled, substrates and inhibitors, for monitoring
the activity and expression of P-gp, respectively, are presented.
PMID- 27514712
TI - Altered Steroid Metabolism and Insulin Signaling in PCOS Endometria: Impact in
Tissue Function.
AB - BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine/ metabolic
disorder characterized by hyperandrogenemia and in most cases, by
hyperinsulinemia in addition to obesity. Besides ovarian dysfunction, endometrial
physiology is also disrupted since this tissue is highly dependent on the action
of steroids; in case of conception cycles, high percentage of abortion is
observed. Because of the endocrine/metabolic alterations, PCOS-women present high
probability to develop hyperplasia and endometrial cancer, where an imbalance of
cell proliferation/apoptosis processes is detected. Additionally, insulin pathway
and the endometrial energetic homeostasis are also compromised. METHODS: The aim
of this review was to report molecular alterations related to insulinresistance
and/or obesity in PCOS-women endometria that could drive to infertility. For
this, several methods were employed: immunohistocytochemistry, qPCR, western
blot, glucoseuptake, cell cultures, among others. RESULTS: Diminished levels and
activity of several insulin signaling pathway molecules, like IRS
1/AS160/PKCzeta, were detected. Concomitantly, a defect in the synthesis and
GLUT4 translocation to cell surface is induced. Oral administration of metformin
(insulin sensitizer) to PCOS-patients increases GLUT4 endometrial levels,
improving fertility of those patients. Another relevant feature is the high
percentage of obesity in PCOS-women; adiponectin is an obesity marker and elicits
an insulin-sensitizer action, being diminished in plasma of obese PCOSwomen
similar to its endometrial level, adiponectin-receptors and APPL1, an adapter
molecule of adiponectin pathway. Moreover, obesity and PCOS can induce a pro
inflammatory environment, exaggerating the alterations in insulin pathway.
CONCLUSION: The evidences obtained in PCOS-endometria clearly indicate that these
molecular defects could partially explain the reproductive failures of these
patients.
PMID- 27514713
TI - Chronic recurrent osteomyelitis: A diagnostic and therapeutic challenge.
AB - INTRODUCTION: Chronic recurrent osteomyelitis (CRO) is a rare disease
characterised by unifocal or multifocal aseptic inflammatory bony lesions.
OBJECTIVE: To evaluate clinical features and response to treatment with non
steroidal anti-inflammatory drugs in patients with CRO. MATERIALS AND METHODS: A
retrospective assessment was conducted on 5 children with OCR over a period of 8
years. They had been diagnosed based on clinical, laboratory findings,
histological study of injuries, and imaging test. RESULTS: Multifocal disease was
observed in 40% of cases, and unifocal in 60%. The large majority (80%) were
male, with a mean age at diagnosis of 13 years (range: 11-15 years). The bones
most frequently affected were the clavicle and tibia, representing 18.2%. The
most common presenting symptom was pain in all patients, with fever being present
in 20% of cases. Imaging studies such as CT and MRI were effective in 100%, and
in all cases the biopsy reported a lymphoplasmacytic infiltrate. After a mean
follow-up of 5.9 years, there was a good treatment response in 100%, with a mean
recurrence at 5.25 months being observed. CONCLUSIONS: The anodyne results of
most clinical studies to assess CRO, and the similarity in clinical presentation
of this with many infectious or tumour diseases makes its diagnosis a real
challenge. On the other hand treatment with NSAIDs can be considered a good
initial therapeutic option.
PMID- 27514715
TI - Prevention of post-disaster sequelae through efficient communication planning:
analysis of information-seeking behaviours in Montana and Alabama.
PMID- 27514716
TI - Dementia-related Bri2 BRICHOS is a versatile molecular chaperone that efficiently
inhibits Abeta42 toxicity in Drosophila.
AB - Formation of fibrils of the amyloid-beta peptide (Abeta) is suggested to play a
central role in neurodegeneration in Alzheimer's disease (AD), for which no
effective treatment exists. The BRICHOS domain is a part of several disease
related proproteins, the most studied ones being Bri2 associated with familial
dementia and prosurfactant protein C (proSP-C) associated with lung amyloid.
BRICHOS from proSP-C has been found to be an efficient inhibitor of Abeta
aggregation and toxicity, but its lung-specific expression makes it unsuited to
target in AD. Bri2 is expressed in the brain, affects processing of Abeta
precursor protein, and increased levels of Bri2 are found in AD brain, but the
specific role of its BRICHOS domain has not been studied in vivo Here, we find
that transgenic expression of the Bri2 BRICHOS domain in the Drosophila central
nervous system (CNS) or eyes efficiently inhibits Abeta42 toxicity. In the
presence of Bri2 BRICHOS, Abeta42 is diffusely distributed throughout the
mushroom bodies, a brain region involved in learning and memory, whereas Abeta42
expressed alone or together with proSP-C BRICHOS forms punctuate deposits outside
the mushroom bodies. Recombinant Bri2 BRICHOS domain efficiently prevents Abeta42
induced reduction in gamma-oscillations in hippocampal slices. Finally, Bri2
BRICHOS inhibits several steps in the Abeta42 fibrillation pathway and prevents
aggregation of heat-denatured proteins, indicating that it is a more versatile
chaperone than proSP-C BRICHOS. These findings suggest that Bri2 BRICHOS can be a
physiologically relevant chaperone for Abeta in the CNS and needs to be further
investigated for its potential in AD treatment.
PMID- 27514714
TI - Three-year follow-up of a randomised controlled trial to reduce excessive weight
gain in the first two years of life: protocol for the POI follow-up study.
AB - BACKGROUND: The Prevention of Overweight in Infancy (POI) study was a four-arm
randomised controlled trial (RCT) in 802 families which assessed whether
additional education and support on sleep (Sleep group); food, physical activity
and breastfeeding (FAB group); or both (Combination group), reduced excessive
weight gain from birth to 2 years of age, compared to usual care (Control group).
The study had high uptake at recruitment (58 %) and retention at 2 years (86 %).
Although the FAB intervention produced no significant effect on BMI or weight
status at 2 years, the odds of obesity were halved in those who received the
sleep intervention, despite no apparent effect on sleep duration. We speculate
that enhanced self-regulatory behaviours may exist in the Sleep group. Self
regulation was not measured in our initial intervention, but extensive measures
have been included in this follow-up study. Thus, the overall aim of the POI
follow-up is to determine the extent to which augmented parental support and
education on infant sleep, feeding, diet, and physical activity in the first 2
years of life reduces BMI at 3.5 and 5 years of age, and to determine the role of
self-regulation in any such relationship. METHODS/DESIGN: We will contact all 802
families and seek renewed consent to participate in the follow-up study. The
families have received no POI intervention since the RCT finished at 2 years of
age. Follow-up data collection will occur when the children are aged 3.5 and 5
years (i.e. up to 3 years post-intervention). Outcomes of interest include child
anthropometry, body composition (DXA scan), diet (validated food frequency
questionnaire), physical activity (accelerometry), sleep (questionnaire and
accelerometry), and self-regulation (questionnaires and neuropsychological
assessment). DISCUSSION: Our follow-up study has been designed primarily to
enable us to determine whether the intriguing benefit of the sleep intervention
suggested at 2 years of age remains as children approach school age. However,
cohort analyses will also investigate how BMI, self-regulation, and sleep
consolidation develop during the early years. This information will be valuable
to researchers and policy makers progressing the field of early childhood obesity
prevention. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00892983 .
PMID- 27514717
TI - Functional and mechanistic roles of the human proton-coupled folate transporter
transmembrane domain 6-7 linker.
AB - The proton-coupled folate transporter (PCFT; SLC46A1) is a folate-proton
symporter expressed in solid tumors and is used for tumor-targeted delivery of
cytotoxic antifolates. Topology modeling suggests that the PCFT secondary
structure includes 12 transmembrane domains (TMDs) with TMDs 6 and 7 linked by an
intracellular loop (positions 236-265) including His247, implicated as
functionally important. Single-cysteine (Cys) mutants were inserted from
positions 241 to 251 in Cys-less PCFT and mutant proteins were expressed in PCFT
null (R1-11) HeLa cells; none were reactive with 2-aminoethyl
methanethiosulfonate biotin, suggesting that the TMD6-7 loop is intracellular.
Twenty-nine single alanine mutants spanning the entire TMD6-7 loop were expressed
in R1-11 cells; activity was generally preserved, with the exception of the 247,
250, and 251 mutants, partly due to decreased surface expression. Coexpression of
PCFT TMD1-6 and TMD7-12 half-molecules in R1-11 cells partially restored
transport activity, although removal of residues 252-265 from TMD7-12 abolished
transport. Chimeric proteins, including a nonhomologous sequence from a thiamine
transporter (ThTr1) inserted into the PCFT TMD6-7 loop (positions 236-250 or 251
265), were active, although replacement of the entire loop with the ThTr1
sequence resulted in substantial loss of activity. Amino acid replacements (Ala,
Arg, His, Gln, and Glu) or deletions at position 247 in wild-type and PCFT-ThTr1
chimeras resulted in differential effects on transport. Collectively, our
findings suggest that the PCFT TMD6-7 connecting loop confers protein stability
and may serve a unique functional role that depends on secondary structure rather
than particular sequence elements.
PMID- 27514719
TI - Who may benefit from robotic gastrectomy?: A subgroup analysis of multicenter
prospective comparative study data on robotic versus laparoscopic gastrectomy.
AB - AIMS: Robotic gastrectomy for gastric cancer has been proven to be a feasible and
safe minimally invasive procedure. However, our previous multicenter prospective
study indicated that robotic gastrectomy is not superior to laparoscopic
gastrectomy. This study aimed to identify which subgroups of patients would
benefit from robotic gastrectomy rather than from conventional laparoscopic
gastrectomy. METHODS: A prospective multicenter comparative study comparing
laparoscopic and robotic gastrectomy was previously conducted. We divided the
patients into subgroups according to obesity, type of gastrectomy performed, and
extent of lymph node dissection. Surgical outcomes were compared between the
robotic and laparoscopic groups in each subgroup. RESULTS: A total of 434
patients were enrolled into the robotic (n = 223) and laparoscopic (n = 211)
surgery groups. According to obesity and gastrectomy type, there was no
difference in the estimated blood loss (EBL), number of retrieved lymph nodes,
complication rate, open conversion rate, and the length of hospital stay between
the robotic and laparoscopic groups. According to the extent of lymph node
dissection, the robotic group showed a significantly lower EBL than did the
laparoscopic group after D2 dissection (P = 0.021), while there was no difference
in EBL in patients that did not undergo D2 dissection (P = 0.365). CONCLUSION:
Patients with gastric cancer undergoing D2 lymph node dissection can benefit from
less blood loss when a robotic surgery system is used.
PMID- 27514720
TI - Prospective assessment of the quality of life in patients treated surgically for
rectal cancer with lower anterior resection and abdominoperineal resection.
AB - INTRODUCTION: Rectal cancer is the most common malignant neoplasm of the
gastrointestinal tract. The aim of the study was to assess the quality of life in
patients undergoing surgical treatment for the rectal cancer, either lower
anterior or abdominoperineal resection. MATERIALS AND METHODS: 100 patients
suffering from rectal cancer were selected for a prospective study (50-APR, 50
LAR). The quality of life was assessed two times: at the admission to the
Department and 6 months following surgery. For assessment of the quality of life,
two standard questionnaires were used, EORT QLQ-C30 and EORTC QLQ-C29. RESULTS:
The studied groups were not different with respect to demographic factors. The
patients who underwent LAR spent less time in hospital (p = 0.00001). The
patients undergoing APR scored less with respect to physical ability (p =
0.0434), cognitive (p = 0.0363) and emotional state (p = 0.0463) and on symptom
scale (nausea and vomiting - p: 0.0199, diarrhea - p: 0.0000, constipation (p =
0.0018)); however, the patients who were treated with LAR scored less on pain
scale (p = 0.0189). The QLQ-C29 questionnaire revealed impaired functioning of
patients 6 months following APR in terms of life chances (p = 0.0000) and
problems with body weight (p = 0.0212). In both groups, the quality of life
improved 6 months after surgery. CONCLUSIONS: LAR is a chance for better quality
of life for many patients. Six months after surgery, the quality of life of
patients improves regardless of the operating method (APR, LAR).
PMID- 27514718
TI - Oral anticoagulation in patients with atrial fibrillation and medical non
neoplastic disease in a terminal stage.
AB - Many patients with non-neoplastic disease develop atrial fibrillation in advanced
stages of their disease. The aim of this study is to determine the factors
associated with the use of oral anticoagulants in patients with atrial
fibrillation and non-neoplastic medical disease in a terminal stage, and whether
their use is associated with a longer survival. Design is prospective,
observational, multicentre study. Patients with atrial fibrillation and non
neoplastic disease (severe not reversible organ insufficiency) in a terminal
stage were included between February 2009 and September 2010. A 6-month follow-up
was carried out. We included 314 patients with a mean (SD) age of 82.6 (7.0)
years. Their mean (SD) scores in CHADS2 and ATRIA scales were 3.4 (1.2) and 4.7
(2.0), respectively. Anticoagulants were prescribed to 112 (37.5 %) patients. The
use of anticoagulants was associated with age (OR 0.96 95 % CI 0.93-0.99, p =
0.046) and to the Barthel index (OR 1.01 95 % CI 1.00-1.02; p = 0.034). After
performing a propensity score matching analysis, 262 patients were included in
the survival analysis. After 6 months, 133 (50.8 %) patients were dead. The
mortality is higher among patients who are not treated with oral anticoagulants
(57.1 vs. 39.4 %; p = 0.006), but it is independently associated only with the
Barthel index score (HR 0.99 95 % CI 0.98-1.00; p = 0.039), delirium (HR 1.60, 95
% CI 1.08-2.36; p = 0.018), anorexia (HR 1.58 95 % CI 1.05-2.38; p = 0.027), and
with the use of calcium channel blockers (HR 0.50 95 % CI 0.30-0.84; p = 0.009).
In patients with atrial fibrillation and non-neoplastic disease in a terminal
stage, the use of oral anticoagulants is not independently associated with a
higher probability of survival.
PMID- 27514721
TI - Immunotherapy of melanoma.
AB - Immunotherapy for advanced melanoma has progressed dramatically in the last five
years with the approval of immune checkpoint inhibitors targeting cytotoxic T
lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD
1). Inhibition of these targets can break cancer-immune tolerance and result in
durable objective responses with significantly improved tolerability over
cytokine-based immunotherapy. Ipilimumab is an inhibitor of CTLA-4 and the first
in-class immune checkpoint inhibitor to demonstrate an improvement in overall
survival in melanoma. Pembrolizumab and nivolumab target PD-1 and have improved
single agent activity and tolerability in comparison to ipilimumab. The
combination of nivolumab and ipilimumab results in even better response rates,
reductions in tumor volume and progression free survival but at the expense of
considerable autoimmune effects. Autoimmune side-effects and non-standard
response kinetics represent a new challenge associated with cancer therapies that
practitioners will have to become more familiar with as checkpoint inhibitors
increasingly become part of mainstream oncological practice. Ongoing areas of
investigation include drug development against novel immune targets; alternative
treatment modalities, such as genetically modified oncolytic viruses;
optimization of immunotherapy combination strategies; and the identification of
reliable biomarkers to better guide treatment selection.
PMID- 27514722
TI - Phenobarbital reduces EEG amplitude and propagation of neonatal seizures but does
not alter performance of automated seizure detection.
AB - OBJECTIVE: Phenobarbital increases electroclinical uncoupling and our preliminary
observations suggest it may also affect electrographic seizure morphology. This
may alter the performance of a novel seizure detection algorithm (SDA) developed
by our group. The objectives of this study were to compare the morphology of
seizures before and after phenobarbital administration in neonates and to
determine the effect of any changes on automated seizure detection rates.
METHODS: The EEGs of 18 term neonates with seizures both pre- and post
phenobarbital (524 seizures) administration were studied. Ten features of
seizures were manually quantified and summary measures for each neonate were
statistically compared between pre- and post-phenobarbital seizures. SDA seizure
detection rates were also compared. RESULTS: Post-phenobarbital seizures showed
significantly lower amplitude (p<0.001) and involved fewer EEG channels at the
peak of seizure (p<0.05). No other features or SDA detection rates showed a
statistical difference. CONCLUSION: These findings show that phenobarbital
reduces both the amplitude and propagation of seizures which may help to explain
electroclinical uncoupling of seizures. The seizure detection rate of the
algorithm was unaffected by these changes. SIGNIFICANCE: The results suggest that
users should not need to adjust the SDA sensitivity threshold after phenobarbital
administration.
PMID- 27514723
TI - School meal provision, health, and cognitive function in a Nordic setting - the
ProMeal-study: description of methodology and the Nordic context.
AB - BACKGROUND: School meals, if both nutritious and attractive, provide a unique
opportunity to improve health equality and public health. OBJECTIVE: To describe
the study rationale, data collection, and background of participants in the study
'Prospects for promoting health and performance by school meals in Nordic
countries' (ProMeal). The general aim was to determine whether overall
healthiness of the diet and learning conditions in children can be improved by
school lunches, and to capture the main concerns regarding school lunches among
children in a Nordic context. DESIGN: A cross-sectional, multidisciplinary study
was performed in Finland, Iceland, Norway, and Sweden on pupils (n=837) born in
2003. RESULTS: In total 3,928 pictures of school lunches were taken to capture
pupils' school lunch intake. A mean of 85% of all parents responded to a
questionnaire about socioeconomic background, dietary intake, and habitual
physical activity at home. Cognitive function was measured on one occasion on 93%
of the pupils during optimal conditions with a Stroop and a Child Operation Span
test. A mean of 169 pupils also did an Integrated Visual and Auditory Continuous
Performance Test after lunch over 3 days. In total, 37,413 10-sec observations of
classroom learning behavior were performed. In addition, 753 empathy-based
stories were written and 78 focus groups were conducted. The pupils had high
socioeconomic status. CONCLUSIONS: This study will give new insights into which
future interventions are needed to improve pupils' school lunch intake and
learning. The study will provide valuable information for policy making, not
least in countries where the history of school meals is shorter than in some of
the Nordic countries.
PMID- 27514724
TI - In vitro and in vivo bimodal effects of docosahexaenoic acid supplements on redox
status and platelet function.
AB - Docosahexaenoic acid (DHA) is a prominent nutrient of marine lipids. Together
with eicosapentaenoic acid, it is recognized as a protective molecule against
atherosclerosis and thrombosis through the regulation of blood cell functions,
especially platelets. Its high unsaturation index may however make it prone to
peroxidation, which is usually considered as deleterious. This short review takes
into consideration this possibility related to DHA concentrations both in vitro
and in vivo. It is suggested that protective effects of DHA on platelet
activation depend on the reduction of oxidative stress, and appear bimodal with
the abolishment of such a protection when DHA is used at relatively high
concentrations.
PMID- 27514725
TI - The mediating role of metacognition in the relationship between executive
function and self-regulated learning.
AB - BACKGROUND: Researchers have demonstrated significant relations among executive
function, metacognition, and self-regulated learning. However, prior research
emphasized the use of indirect measures of executive function and did not
evaluate how specific executive functions are related to participants' self
regulated learning. AIMS: The primary goals of the current study were to examine
and test the relations among executive function, metacognition, and self
regulated learning as well as to examine how self-regulated learning is informed
by executive function. SAMPLE: The sample comprised 117 undergraduate students
attending a large, Mid-Atlantic research university in the United States.
METHODS: Participants were individually administered direct and indirect measures
of executive function, metacognition, and self-regulated learning. A mediation
model specifying the relations among the regulatory constructs was proposed.
RESULTS: In multiple linear regression analyses, executive function predicted
metacognition and self-regulated learning. Direct measures of inhibition and
shifting accounted for a significant amount of the variance in metacognition and
self-regulated learning beyond an indirect measure of executive functioning.
Separate mediation analyses indicated that metacognition mediated the
relationship between executive functioning and self-regulated learning as well as
between specific executive functions and self-regulated learning. CONCLUSIONS:
The findings of this study are supported by previous research documenting the
relations between executive function and self-regulated learning, and extend
prior research by examining the manner in which executive function and self
regulated learning are linked. The findings provide initial support for executive
functions as key processes, mediated by metacognition, that predict self
regulated learning. Implications for the contribution of executive functions to
self-regulated learning are discussed.
PMID- 27514726
TI - Association between obesity and asthma - epidemiology, pathophysiology and
clinical profile.
AB - Obesity is a risk factor for asthma, and obese asthmatics have lower disease
control and increased symptom severity. Several putative links have been
proposed, including genetics, mechanical restriction of the chest and the intake
of corticosteroids. The most consistent evidence, however, comes from studies of
cytokines produced by the adipose tissue called adipokines. Adipokine imbalance
is associated with both proinflammatory status and asthma. Although reverse
causation has been proposed, it is now acknowledged that obesity precedes asthma
symptoms. Nevertheless, prenatal origins of both conditions complicate the search
for causality. There is a confirmed role of neuro-immune cross-talk mediating
obesity-induced asthma, with leptin playing a key role in these processes.
Obesity-induced asthma is now considered a distinct asthma phenotype. In fact, it
is one of the most important determinants of asthma phenotypes. Two main
subphenotypes have been distinguished. The first phenotype, which affects adult
women, is characterised by later onset and is more likely to be non-atopic. The
childhood obesity-induced asthma phenotype is characterised by primary and
predominantly atopic asthma. In obesity-induced asthma, the immune responses are
shifted towards T helper (Th) 1 polarisation rather than the typical atopic Th2
immunological profile. Moreover, obese asthmatics might respond differently to
environmental triggers. The high cost of treatment of obesity-related asthma, and
the burden it causes for the patients and their families call for urgent
intervention. Phenotype-specific approaches seem to be crucial for the success of
prevention and treatment.
PMID- 27514727
TI - Geographic variation in cost of care for pituitary tumor surgery.
AB - PURPOSE: Geography is known to affect cost of care in surgical procedures.
Understanding the relationship between geography and hospital costs is pertinent
in the effort to reduce healthcare costs. We studied the geographic variation in
cost for transsphenoidal pituitary surgery in hospitals across New York State.
METHODS: Using the Healthcare Cost and Utilization Project State Inpatient
Database for New York from 2008 to 2011, we analyzed records of patients who
underwent elective transsphenoidal pituitary tumor surgery and were discharged to
home or self-care. N.Y. State was divided into five geographic regions: Buffalo,
Rochester, Syracuse, Albany, and Downstate. These five regions were compared
according to median charge and cost per day. RESULTS: From 2008 to 2011, 1803
transsphenoidal pituitary tumor surgeries were performed in New York State. Mean
patient age was 50.7 years (54 % were female). Adjusting prices for length of
stay, there was substantial variation in prices. Median charges per day ranged
from $8485 to $13,321 and median costs per day ranged from $2962 to $6837 between
the highest and lowest regions from 2008 to 2011. CONCLUSION: Within New York
State, significant geographic variation exists in the cost for transsphenoidal
pituitary surgery. The significance of and contributors to such variation is an
important question for patients, providers, and policy makers. Transparency of
hospital charges, costs, and average length of stay for procedures to the public
provides useful information for informed decision-making, especially for a highly
portable disease entity like pituitary tumors.
PMID- 27514728
TI - A new survivin tracer tracks, delocalizes and captures endogenous survivin at
different subcellular locations and in distinct organelles.
AB - Survivin, the smallest member of the inhibitor of apoptosis protein family, plays
a central role during mitosis and exerts a cytoprotective function. Survivin is
highly expressed in most cancer types and contributes to multiple facets of
carcinogenesis. The molecular mechanisms underlying its highly diverse functions
need to be extensively explored, which is crucial for rational design of future
personalized therapeutics. In this study, we have generated an alpaca survivin
nanobody (SVVNb8) that binds with low nanomolar affinity to its target. When
expressed as an intrabody in HeLa cells, SVVNb8 faithfully tracks survivin during
different phases of mitosis without interfering with survivin function.
Furthermore, coupling SVVNb8 with a subcellular delocalization tag efficiently
redirects endogenous survivin towards the nucleus, the cytoplasm, peroxisomes and
even to the intermembrane space of mitochondria where it presumably interacts
with resident mitochondrial survivin. Based on our findings, we believe that
SVVNb8 is an excellent instrument to further elucidate survivin biology and
topography, and can serve as a model system to investigate mitochondrial and
peroxisomal (survivin) protein import.
PMID- 27514730
TI - Scotland prioritises action on child poverty.
PMID- 27514729
TI - Environment shapes the fecal microbiome of invasive carp species.
AB - BACKGROUND: Although the common, silver, and bighead carps are native and
sparsely distributed in Eurasia, these fish have become abundant and invasive in
North America. An understanding of the biology of these species may provide
insights into sustainable control methods. The animal-associated microbiome plays
an important role in host health. Characterization of the carp microbiome and the
factors that affect its composition is an important step toward understanding the
biology and interrelationships between these species and their environments.
RESULTS: We compared the fecal microbiomes of common, silver, and bighead carps
from wild and laboratory environments using Illumina sequencing of bacterial 16S
ribosomal RNA (rRNA). The fecal bacterial communities of fish were diverse, with
Shannon indices ranging from 2.3 to 4.5. The phyla Proteobacteria, Firmicutes,
and Fusobacteria dominated carp guts, comprising 76.7 % of total reads.
Environment played a large role in shaping fecal microbial community composition,
and microbiomes among captive fishes were more similar than among wild fishes.
Although differences among wild fishes could be attributed to feeding
preferences, diet did not strongly affect microbial community structure in
laboratory-housed fishes. Comparison of wild- and lab-invasive carps revealed
five shared OTUs that comprised approximately 40 % of the core fecal microbiome.
CONCLUSIONS: The environment is a dominant factor shaping the fecal bacterial
communities of invasive carps. Captivity alters the microbiome community
structure relative to wild fish, while species differences are pronounced within
habitats. Despite the absence of a true stomach, invasive carp species exhibited
a core microbiota that warrants future study.
PMID- 27514731
TI - Percutaneous right ventricular assist device in sepsis due to right ventricular
failure and pulmonary hypertension.
PMID- 27514732
TI - The Validity and Reliability of Turkish Version of the Chemotherapy-induced Taste
Alteration Scale (CiTAS).
AB - The study was aimed to assess the validity and reliability of the Turkish version
of the Chemotherapy-induced Taste Alteration Scale (CiTAS), and was conducted on
adult patients receiving chemotherapy ( N = 184) in the Chemotherapy Unit and
Hematology Clinic (Outpatient) of a university hospital between December 2013 and
May 2014. The results showed that the Cronbach's alpha coefficient (.869) was
satisfactory. The alpha value was .89 for the Decline in Basic Taste subscale,
.70 for Discomfort subscale, .82 for Phantogeusia and Parageusia subscale, and
.72 for General Taste Alterations subscale. The coefficients of the relationship
between test-retest reliability results were significantly high ( r = .939, n =
28). The Turkish version of the CiTAS was a sufficient and suitable tool in
evaluating the taste alterations associated with chemotherapy.
PMID- 27514733
TI - In vitro differentiation potential of human haematopoietic CD34(+) cells towards
pancreatic beta-cells.
AB - Haematopoietic stem cells (HSCs) possess multipotent ability to differentiate
into various types of cells on providing appropriate niche. In the present study,
the differentiating potential of human HSCs into beta-cells of islets of
langerhans was explored. Human HSCs were apheretically isolated from a donor and
cultured. Phenotypic characterization of CD34 glycoprotein in the growing
monolayer HSCs was confirmed by immunocytochemistry and flow cytometry
techniques. HSCs were induced by selection with beta cell differentiating medium
(BDM), which consists of epidermal growth factor (EGF), fibroblast growth factor
(FGF), transferrin, Triiodo-l-Tyronine, nicotinamide and activin A. Distinct
morphological changes of differentiated cells were observed on staining with
dithizone (DTZ) and expression of PDX1, insulin and synaptophysin was confirmed
by immunocytochemistry. Quantitative real-time polymerase chain reaction (qRT
PCR) analysis revealed distinct expression of specific beta-cell markers,
pancreatic and duodenal homeobox-1 (PDX1), glucose transporter-2 (GLUT-2),
synaptophysin (SYP) and insulin (INS) in these differentiated cells compared to
HSCs. Further, these cells exhibited elevated expression of INS gene at 10 mM
glucose upon inducing with different glucose concentrations. The prominent
feature of the obtained beta-cells was the presence of glucose sensors, which was
determined by glucokinase activity and high glucokinase activity compared with
CD34(+) stem cells. These findings illustrate the differentiation of CD34(+) HSCs
into beta-cells of islets of langerhans.
PMID- 27514734
TI - I Remember Better When I Paint.
PMID- 27514736
TI - Outcomes After Revision Hip Arthroscopic Surgery in Adolescent Patients Compared
With a Matched Cohort Undergoing Primary Arthroscopic Surgery.
AB - BACKGROUND: The incidence of hip arthroscopic surgery is increasing in the young
athlete. This has also led to increased numbers of revision hip arthroscopic
surgery. HYPOTHESIS/PURPOSE: The purpose of this study was to describe the
outcomes after revision hip arthroscopic surgery in patients <=18 years of age in
comparison to a matched cohort of patients undergoing primary hip arthroscopic
surgery. Our hypothesis was that patients undergoing revision hip arthroscopic
surgery would demonstrate similar outcomes to those patients undergoing primary
hip arthroscopic surgery. STUDY DESIGN: Cohort study; Level of evidence, 3.
METHODS: Patients were included in the study if they underwent revision hip
arthroscopic surgery by a single surgeon and did not undergo prior open hip
surgery. Each patient in the revision hip arthroscopic surgery cohort was matched
with 2 patients undergoing primary hip arthroscopic surgery from the same
institution. Cohorts were matched by age, sex, and year of surgery.
Preoperatively and at a minimum follow-up of 2 years, outcome scores were
collected. The primary outcome measure was the Hip Outcome Score for activities
of daily living scale (HOS-ADL), a self-reported validated outcome instrument, in
addition to the HOS for sports scale (HOS-Sport), modified Harris Hip Score
(mHHS), and 12-Item Short Form Health Survey Physical Component Summary (SF-12
PCS). RESULTS: Forty-two patients were included in the revision group and were
matched with 84 patients in the primary group. The mean age in both groups was 16
years (range, 14-18 years). All female patients in the study were >=14 years of
age, and all male patients were >=16 years of age. In patients undergoing
revision, 13 underwent 1 prior surgical procedure, 22 underwent 2 prior surgical
procedures, and 7 underwent >=3 prior surgical procedures. The mean time from
last surgery to revision was 18.7 months (range, 4.7-74 months). Eleven patients
(26%) had prior femoroacetabular impingement treated, which required osteoplasty
or rim trimming at revision. Subsequent hip arthroscopic surgery was reported in
3 of 84 (4%) patients in the primary group and 6 of 42 (14%) patients in the
revision group (P = .162). The mean follow-up in the revision group was 43 +/- 17
months, and scores significantly improved (HOS-ADL: 59.6 to 77.6; HOS-Sport: 37.6
to 64.8; mHHS: 55.3 to 74.3; SF-12 PCS: 41.0 to 50.4; P < .05). The mean follow
up in the primary group was 45 +/- 18 months, and all scores significantly
improved (HOS-ADL: 65.8 to 87.4; HOS-Sport: 46.3 to 79.9; mHHS: 57.5 to 84.2; SF
12 PCS: 39.0 to 51.8; P < .05). At follow-up, there were no significant
differences between the primary and revision groups for the HOS-ADL values (P =
.051) and SF-12 PCS values (P = .846). Patients in the primary group had
significantly higher HOS-Sport values (P = .008), mHHS values (P = .008), and
patient satisfaction (P = .008). Patients who underwent 1 prior hip arthroscopic
procedure had a higher mean postoperative mHHS value (79.5 vs 72, respectively),
HOS-ADL value (91.2 vs 73.4, respectively), and HOS-Sport value (76 vs 60,
respectively) (P < .05) compared with those who underwent more than 1 prior
procedure. Median patient satisfaction was 9.0 (range, 2-10) in the primary group
and 8.0 (range, 2-10) in the revision group. CONCLUSION: In conclusion, young
patients who required revision hip arthroscopic surgery showed significant
improvement in patient-reported outcome scores; however, final outcome scores in
the revision group for sport activity, general health, and satisfaction were
lower than those in the primary group. Patients who underwent 1 revision surgical
procedure had higher outcome scores than patients who underwent more than 1
revision surgical procedure.
PMID- 27514737
TI - Results of Bone Peg Grafting for Capitellar Osteochondritis Dissecans in
Adolescent Baseball Players.
AB - BACKGROUND: Bone peg grafting (BPG) has been advocated for early-stage humeral
capitellar osteochondritis dissecans (COCD). However, the clinical and
radiological results of BPG, along with its indications, have not been described
in detail. HYPOTHESIS: COCD classified as International Cartilage Repair Society
(ICRS) osteochondritis dissecans (OCD) I or II in adolescent baseball players can
be treated successfully by BPG. STUDY DESIGN: Case series; Level of evidence, 4
METHODS: Eleven male baseball players (age range at surgery, 13-16 years) who
underwent BPG for COCD were enrolled in this study. No improvement had been seen
in any patient after 6 months of preoperative nonthrowing observation. During
surgery, 2 to 5 bone pegs were inserted into the COCD lesion after confirmation
of lesion stability to the bony floor. All patients were directly evaluated at 12
and 24 months after surgery by physical findings, radiological prognosis, and
magnetic resonance imaging (MRI). RESULTS: Of the 11 patients, 10 could return to
comparable baseball ability levels within 12 months. The Timmerman-Andrews score
improved significantly from a mean +/- SD of 171.8 +/- 12.1 preoperatively to
192.3 +/- 6.5 at the final observation. Radiological healing of the lesions was
determined as complete in 8 patients and partial in 3. Patients possessing a
centrally positioned lesion or a lesion <75% of the size of the capitellum tended
most strongly to achieve complete radiological healing, while growth plate status
appeared unrelated to outcome. The mean Henderson MRI score improved from 6.3 +/-
1.5 to 4.8 +/- 1.6 at 12 and 24 months after BPG, respectively. MRI findings also
suggested that remodeling of COCD lesions had continued to up to 24 months
postoperatively. CONCLUSION: BPG enabled 91% of COCD patients with ICRS OCD I or
II to return to preoperative baseball abilities within 12 months. Integration of
the grafted site may continue until at least 24 months postoperatively. An ICRS
OCD I or II lesion with central positioning and/or occupying <75% of the size of
the capitellum in the coronal plane is a good indication for BPG.
PMID- 27514738
TI - Geometric Risk Factors Associated With Noncontact Anterior Cruciate Ligament
Graft Rupture.
AB - BACKGROUND: Anterior cruciate ligament (ACL) graft rupture occurs at a high rate,
especially in young athletes. The geometries of the tibial plateau and femoral
intercondylar notch are risk factors for first-time ACL injury; however, little
is known about the relationship between these geometries and risk of ACL graft
rupture. HYPOTHESIS: The geometric risk factors for noncontact graft rupture are
similar to those previously identified for first-time noncontact ACL injury, and
sex-specific differences exist. STUDY DESIGN: Case-control study; Level of
evidence, 3. METHODS: Eleven subjects who suffered a noncontact ACL graft rupture
and 44 subjects who underwent ACL reconstruction but did not experience graft
rupture were included in the study. Using magnetic resonance imaging, the
geometries of the tibial plateau subchondral bone, articular cartilage, meniscus,
tibial spines, and femoral notch were measured. Risk factors associated with ACL
graft rupture were identified using Cox regression. RESULTS: The following were
associated with increased risk of ACL graft injury in males: increased posterior
inferior-directed slope of the articular cartilage in the lateral tibial plateau
measured at 2 locations (hazard ratio [HR] = 1.50, P = .029; HR = 1.39, P =
.006), increased volume (HR = 1.45, P = .01) and anteroposterior length (HR =
1.34, P = .0023) of the medial tibial spine, and increased length (HR = 1.18, P =
.0005) and mediolateral width (HR = 2.19, P = .0004) of the lateral tibial spine.
In females, the following were associated with increased risk of injury:
decreased volume (HR = 0.45, P = .02) and height (HR = 0.46, P = .02) of the
medial tibial spine, decreased slope of the lateral tibial subchondral bone (HR =
0.72, P = .01), decreased height of the posterior horn of the medial meniscus (HR
= 0.09, P = .001), and decreased intercondylar notch width at the anterior
attachment of the ACL (HR = 0.72, P = .02). CONCLUSION: The geometric risk
factors for ACL graft rupture are different for males and females. For females, a
decreased femoral intercondylar notch width and a decreased height of the
posterior medial meniscus were risk factors for ACL graft rupture that have also
been found to be risk factors for first-time injury. There were no risk factors
in common between ACL graft injury and first-time ACL injury for males.
PMID- 27514739
TI - Adolescents' health choices related rights, duties and responsibilities: An
integrative review.
AB - BACKGROUND: Although the link between adolescents' health choices in relation to
rights, duties and responsibilities is acknowledged, little is studied in this
subject. AIM: To identify, describe and synthesize previous studies on
adolescents' health choices in relation to rights, duties and responsibilities.
Ethical considerations: Ethical approval is not needed as it is an integrative
review of published literature. METHOD: The integrative review was used to review
and synthesize current knowledge. Electronic and manual searches from 2009 to
March 2014 were used to systematically identify earlier studies. RESULTS: The
review identified 13 studies. Adolescents' health choices were linked to
unsuccessfully exercised rights, arising from questioned autonomy and freedom,
and their duties were hardly mentioned. CONCLUSION: Research into adolescents'
health choices in relation to their rights, duties and responsibilities is still
methodologically fragmented. In future, more research is needed to support
adolescents' health promotion initiatives and increase their involvement
opportunities.
PMID- 27514740
TI - Lessons learned from nurses' requests for ethics consultation: Why did they call
and what did they value?
AB - BACKGROUND: An ongoing challenge for clinical ethics consultation is learning how
colleagues in other healthcare professions understand, make use of, and evaluate
clinical ethics consultation services. AIM: In pursuing such knowledge as part of
clinical ethics consultation service quality assessment, clinical ethics
consultation services can learn important information about the issues and
concerns that prompt colleagues to request ethics consultation. Such knowledge
allows for greater outreach, education, and responsiveness by clinical ethics
consultation services to the concerns of clinician colleagues. DESIGN: This
quality assessment project explores consultation requests and follow-up
questionnaire responses voluntarily submitted from nurses who requested clinical
ethics consultation. We present qualitative data analyzed using content analysis
and constant comparison methods to identify key concerns that prompted requests
as well as common themes among nurse requestors' evaluations of what was most
important in clinical ethics consultations. Participants and context: A total of
41 nurses requesting clinical ethics consultation and 15 who returned the follow
up questionnaire. Ethical considerations: Our Office of Research Compliance and
Quality Improvement determined that our project was not considered human subjects
research and so did not require institutional review board approval or exemption.
However, efforts were made to avoid any sense of coercion and all data were de
identified prior to analysis. FINDINGS: Our analysis revealed six main categories
of issues that prompted nurses' requests for ethics consultation, as well as
unifying themes around nurses' experiences, advocacy, and family support while
caring for patients in the intersections of patients, families, and physicians.
DISCUSSION: The insights gained from analyzing nurses' requests for and responses
to clinical ethics consultation may serve as a resource for clinical ethics
consultation services seeking to identify, respond to, and educate regarding
issues of importance to nurse colleagues and may be a resource for nursing
administrators and leadership seeking to identify and address common ethical
issues nurses face. CONCLUSION: Ongoing work on clinical ethics consultation
service quality improvement and engagement with our nursing colleagues about
their concerns prompting-and their evaluations of-clinical ethics consultation
are necessary.
PMID- 27514741
TI - Nurse's perceptions of organisational barriers to delivering compassionate care:
A qualitative study.
AB - BACKGROUND: Compassionate care is an international priority of healthcare
professionals. There is little understanding about how workplace issues impact
provision of compassionate care in nursing practice. Therefore, it is important
to address the workplace issues and organizational factors which may hinder
compassionate care delivery within nursing practice. OBJECTIVE: The aim of this
study was to explore workplace and organizational barriers to compassionate care
from the nurses' perspective. RESEARCH DESIGN: The study used a qualitative
exploratory design, and data were analyzed by conventional content analysis.
Participants and research context: A total of 15 nurses working in different
fields of nursing were recruited from four hospitals at northwest of Iran.
Participants were selected by purposive sampling. Semistructured interviews were
conducted for data collection. Ethical consideration: Ethical approval of this
study was gained from the Ethical Review Board of Tabriz University of Medical
Sciences. FINDINGS: The main theme which emerged from data analysis was
"unsupportive organizational culture." This theme had two main categories
including "excessive workload alongside inadequate staffing" and "the lack of
value on compassionate care." DISCUSSION: Organizational barriers to development
of compassionate in clinical practice were identified in this study. A closer
examination of these barriers is required to move compassionate practice from an
individual responsibility to a collective responsibility that is owned and shared
by organizations. CONCLUSION: For compassionate care to flourish, policy makers,
managers, and healthcare providers must foster an organizational atmosphere
conducive to compassionate care.
PMID- 27514742
TI - Formation energies and electronic structure of intrinsic vacancy defects and
oxygen vacancy clustering in BaZrO3.
AB - Ab initio density functional theory calculations are employed for exploring the
thermodynamic stability, vacancy defect formation energy and electronic structure
of pristine and non-stoichiometric BaZrO3. The electronic properties of BaZrO3
show the hole-doped and insulating nature of cation and oxygen vacancies,
respectively. The changes in the electronic properties of intrinsic vacancy
containing BaZrO3 are analyzed in terms of electronic band structure, charge
density and effective Bader charges. The relative stability of the formation of
charge neutral and fully charged intrinsic vacancy defects in BaZrO3 is
investigated in different chemical growth environments and the full and partial
Schottky reactions are computed. Calculations are also performed to study the
effects of oxygen vacancy clustering in different crystallographic planes. These
calculations enable us to predict n-type conductivity in non-stoichiometric
BaZrO3, which is useful for tailoring the electrical conduction of this material.
Our results suggest that the semiconducting, p- and n-type character of BaZrO3
can be realized to enhance its device application by means of intentional
incorporation of vacancy defects.
PMID- 27514743
TI - TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.
AB - Mammalian chromosome ends are protected by a specialized nucleoprotein complex
called telomeres. Both shelterin, a telomere-specific multi-protein complex, and
higher order telomeric chromatin structures combine to stabilize the chromosome
ends. Here, we showed that TRF2, a component of shelterin, binds to core histones
to protect chromosome ends from inappropriate DNA damage response and loss of
telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly
binds to the globular domain of core histones. The conserved arginine residues in
the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with
these arginine residues substituted by alanine lost the ability to protect
telomeres and induced rapid telomere shortening caused by the cleavage of a loop
structure of the telomeric chromatin. These findings showed a previously
unnoticed interaction between the shelterin complex and nucleosomal histones to
stabilize the chromosome ends.
PMID- 27514744
TI - Functional and Structural Characterization of Novel Type of Linker Connecting
Capsid and Nucleocapsid Protein Domains in Murine Leukemia Virus.
AB - The assembly of immature retroviral particles is initiated in the cytoplasm by
the binding of the structural polyprotein precursor Gag with viral genomic RNA.
The protein interactions necessary for assembly are mediated predominantly by the
capsid (CA) and nucleocapsid (NC) domains, which have conserved structures. In
contrast, the structural arrangement of the CA-NC connecting region differs
between retroviral species. In HIV-1 and Rous sarcoma virus, this region forms a
rod-like structure that separates the CA and NC domains, whereas in Mason-Pfizer
monkey virus, this region is densely packed, thus holding the CA and NC domains
in close proximity. Interestingly, the sequence connecting the CA and NC domains
in gammaretroviruses, such as murine leukemia virus (MLV), is unique. The
sequence is called a charged assembly helix (CAH) due to a high number of
positively and negatively charged residues. Although both computational and
deletion analyses suggested that the MLV CAH forms a helical conformation, no
structural or biochemical data supporting this hypothesis have been published.
Using an in vitro assembly assay, alanine scanning mutagenesis, and biophysical
techniques (circular dichroism, NMR, microcalorimetry, and electrophoretic
mobility shift assay), we have characterized the structure and function of the
MLV CAH. We provide experimental evidence that the MLV CAH belongs to a group of
charged, E(R/K)-rich, single alpha-helices. This is the first single alpha-helix
motif identified in viral proteins.
PMID- 27514745
TI - Structural Insight into the 14-3-3 Protein-dependent Inhibition of Protein Kinase
ASK1 (Apoptosis Signal-regulating kinase 1).
AB - Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of
the mitogen-activated protein kinase kinase kinase (MAP3K) family, regulates
diverse physiological processes. The activity of ASK1 is triggered by various
stress stimuli and is involved in the pathogenesis of cancer, neurodegeneration,
inflammation, and diabetes. ASK1 forms a high molecular mass complex whose
activity is, under non-stress conditions, suppressed through interaction with
thioredoxin and the scaffolding protein 14-3-3. The 14-3-3 protein binds to the
phosphorylated Ser-966 motif downstream of the ASK1 kinase domain. The role of 14
3-3 in the inhibition of ASK1 has yet to be elucidated. In this study we
performed structural analysis of the complex between the ASK1 kinase domain
phosphorylated at Ser-966 (pASK1-CD) and the 14-3-3zeta protein. Small angle x
ray scattering (SAXS) measurements and chemical cross-linking revealed that the
pASK1-CD.14-3-3zeta complex is dynamic and conformationally heterogeneous. In
addition, structural analysis coupled with the results of phosphorus NMR and time
resolved tryptophan fluorescence measurements suggest that 14-3-3zeta interacts
with the kinase domain of ASK1 in close proximity to its active site, thus
indicating this interaction might block its accessibility and/or affect its
conformation.
PMID- 27514746
TI - Plasticity of Myeloid Cells during Oral Barrier Wound Healing and the Development
of Bisphosphonate-related Osteonecrosis of the Jaw.
AB - Injury to the barrier tissue initiates a rapid distribution of myeloid immune
cells from bone marrow, which guide sound wound healing. Bisphosphonates, a
widely used anti-bone resorptive drug with minimal systemic side effects, have
been linked to an abnormal wound healing in the oral barrier tissue leading to,
in some cases, osteonecrosis of the jaw (ONJ). Here we report that the
development of ONJ may involve abnormal phenotypic plasticity of Ly6G+/Gr1+
myeloid cells in the oral barrier tissue undergoing tooth extraction wound
healing. A bolus intravenous zoledronate (ZOL) injection to female C57Bl/6 mice
followed by maxillary first molar extraction resulted in the development of ONJ
like lesion during the second week of wound healing. The multiplex assay of
dissociated oral barrier cells exhibited the secretion of cytokines and
chemokines, which was significantly modulated in ZOL mice. Tooth extraction
induced distribution of Ly6G+/Gr1+ cells in the oral barrier tissue increased in
ZOL mice at week 2. ONJ-like lesion in ZOL mice contained Ly6G+/Gr1+ cells with
abnormal size and morphology as well as different flow cytometric staining
intensity. When anti-Ly6G (Gr1) antibody was intraperitoneally injected for 5
days during the second week of tooth extraction, CD11b+GR1(hi) cells in bone
marrow and Ly6G+ cells in the oral barrier tissue were depleted, and the
development of ONJ-like lesion was significantly attenuated. This study suggests
that local modulation of myeloid cell plasticity in the oral barrier tissue may
provide the basis for pathogenesis and thus therapeutic as well as preventive
strategy of ONJ.
PMID- 27514747
TI - Retinal Hypercholesterolemia Triggers Cholesterol Accumulation and Esterification
in Photoreceptor Cells.
AB - The process of vision is impossible without the photoreceptor cells, which have a
unique structure and specific maintenance of cholesterol. Herein we report on the
previously unrecognized cholesterol-related pathway in the retina discovered
during follow-up characterizations of Cyp27a1(-/-)Cyp46a1(-/-) mice. These
animals have retinal hypercholesterolemia and convert excess retinal cholesterol
into cholesterol esters, normally present in the retina in very small amounts. We
established that in the Cyp27a1(-/-)Cyp46a1(-/-) retina, cholesterol esters are
generated by and accumulate in the photoreceptor outer segments (OS), which is
the retinal layer with the lowest cholesterol content. Mouse OS were also found
to express the cholesterol-esterifying enzyme acyl-coenzyme A:cholesterol
acyltransferase (ACAT1), but not lecithin-cholesterol acyltransferase (LCAT), and
to differ from humans in retinal expression of ACAT1. Nevertheless, cholesterol
esters were discovered to be abundant in human OS. We suggest a mechanism for
cholesterol ester accumulation in the OS and that activity impairment of ACAT1 in
humans may underlie the development of subretinal drusenoid deposits, a hallmark
of age-related macular degeneration, which is a common blinding disease. We
generated Cyp27a1(-/-)Cyp46a1(-/-)Acat1(-/-) mice, characterized their retina by
different imaging modalities, and confirmed that unesterified cholesterol does
accumulate in their OS and that there is photoreceptor apoptosis and OS
degeneration in this line. Our results provide insights into the retinal response
to local hypercholesterolemia and the retinal significance of cholesterol
esterification, which could be cell-specific and both beneficial and detrimental
for retinal structure and function.
PMID- 27514748
TI - BnPME is progressively induced after microspore reprogramming to embryogenesis,
correlating with pectin de-esterification and cell differentiation in Brassica
napus.
AB - BACKGROUND: Pectins are one of the main components of plant cell walls. They are
secreted to the wall as highly methylesterified forms that can be de-esterified
by pectin methylesterases (PMEs). The degree of methylesterification of pectins
changes during development, PMEs are involved in the cell wall remodeling that
occurs during diverse plant developmental processes. Nevertheless, the functional
meaning of pectin-related wall remodeling in different cell types and processes
remains unclear. In vivo, the microspore follows the gametophytic pathway and
differentiates to form the pollen grain. In vitro, the microspore can be
reprogrammed by stress treatments becoming a totipotent cell that starts to
proliferate and follows the embryogenic pathway, a process known as microspore
embryogenesis. RESULTS: To investigate if the change of developmental programme
of the microspore towards embryogenesis involves changes in pectin esterification
levels, which would cause the cell wall remodeling during the process, in the
present study, dynamics of PME expression and degrees of pectin esterification
have been analysed during microspore embryogenesis and compared with the
gametophytic development, in Brassica napus. A multidisciplinary approach has
been adopted including BnPME gene expression analysis by quantitative RT-PCR,
fluorescence in situ hybridization, immuno-dot-blot and immunofluorescence with
JIM5 and JIM7 antibodies to reveal low and highly-methylesterified pectins. The
results showed that cell differentiation at advanced developmental stages
involved induction of BnPME expression and pectin de-esterification, processes
that were also detected in zygotic embryos, providing additional evidence that
microspore embryogenesis mimics zygotic embryogenesis. By contrast, early
microspore embryogenesis, totipotency and proliferation were associated with low
expression of BnPME and high levels of esterified pectins. CONCLUSIONS: The
results show that the change of developmental programme of the microspore
involves changes in pectin esterification associated with proliferation and
differentiation events, which may cause the cell wall remodeling during the
process. The findings indicate pectin-related modifications in the cell wall
during microspore embryogenesis, providing new insights into the role of pectin
esterification and cell wall configuration in microspore totipotency,
embryogenesis induction and progression.
PMID- 27514749
TI - Validation and Comparison of Seven Mortality Prediction Models for Hospitalized
Patients With Acute Decompensated Heart Failure.
AB - BACKGROUND: Heart failure (HF) inpatient mortality prediction models can help
clinicians make treatment decisions and researchers conduct observational
studies; however, published models have not been validated in external
populations. METHODS AND RESULTS: We compared the performance of 7 models that
predict inpatient mortality in patients hospitalized with acute decompensated
heart failure: 4 HF-specific mortality prediction models developed from 3
clinical databases (ADHERE [Acute Decompensated Heart Failure National Registry],
EFFECT study [Enhanced Feedback for Effective Cardiac Treatment], and GWTG-HF
registry [Get With the Guidelines-Heart Failure]); 2 administrative HF mortality
prediction models (Premier, Premier+); and a model that uses clinical data but is
not specific for HF (Laboratory-Based Acute Physiology Score [LAPS2]). Using a
multihospital, electronic health record-derived data set (HealthFacts [Cerner
Corp], 2010-2012), we identified patients >=18 years admitted with HF. Of 13 163
eligible patients, median age was 74 years; half were women; and 27% were black.
In-hospital mortality was 4.3%. Model-predicted mortality ranges varied: Premier+
(0.8%-23.1%), LAPS2 (0.7%-19.0%), ADHERE (1.2%-17.4%), EFFECT (1.0%-12.8%), GWTG
Eapen (1.2%-13.8%), and GWTG-Peterson (1.1%-12.8%). The LAPS2 and Premier models
outperformed the clinical models (C statistics: LAPS2 0.80 [95% confidence
interval 0.78-0.82], Premier models 0.81 [95% confidence interval 0.79-0.83] and
0.76 [95% confidence interval 0.74-0.78], and clinical models 0.68 to 0.70).
CONCLUSIONS: Four clinically derived, inpatient, HF mortality models exhibited
similar performance, with C statistics near 0.70. Three other models, 1 developed
in electronic health record data and 2 developed in administrative data, also
were predictive, with C statistics from 0.76 to 0.80. Because every model
performed acceptably, the decision to use a given model should depend on
practical concerns and intended use.
PMID- 27514750
TI - Implications of Using Different Definitions on Outcomes in Worsening Heart
Failure.
AB - BACKGROUND: In-hospital worsening heart failure (WHF) is an important event that
has inconsistent definitions used across trials. We used data from 2 acute heart
failure (HF) trials from the National Institutes of Health HF Network, DOSE
(Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization
Strategies), to understand event rates associated with different WHF definitions.
METHODS AND RESULTS: We pooled data from 668 patients in DOSE and ROSE and
assessed the relationship between WHF and the composite end point of
rehospitalization, emergency room visits for HF, and mortality through 60 days.
We also assessed for a differential relationship between the timing of WHF
development and outcomes. The overall incidence of WHF was 14.6% (24.1% in DOSE,
6.3% in ROSE, and 5.0% in DOSE using the ROSE definition). WHF was associated
with an increase in the composite end point (hazard ratio [HR], 1.64; 95%
confidence interval [CI], 1.11-2.42; P=0.01). However, the association between
WHF and outcomes was significantly stronger in ROSE than in DOSE (HR, 2.67; 95%
CI, 1.45-4.91; P<0.01 and HR, 1.28; 95% CI, 0.79-2.08; P=0.31, respectively).
Development of WHF between baseline to 24 hours compared with 24 to 48 hours or
48 to 72 hours demonstrated a trend toward improved outcomes (HR, 0.49; 95% CI,
0.21-1.17; P=0.11 and HR, 0.45; 95% CI, 0.20-1.04; P=0.06, respectively).
CONCLUSIONS: A WHF definition that excluded the intensification of diuretics
resulted in a lower event rate but a stronger association with outcomes. These
data support the need for continued efforts to standardize WHF definitions in
clinical trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
Unique identifiers: NCT00577135 (DOSE) and NCT01132846 (ROSE).
PMID- 27514752
TI - Model Building as an Educational Hobby.
PMID- 27514751
TI - Multistate Model to Predict Heart Failure Hospitalizations and All-Cause
Mortality in Outpatients With Heart Failure With Reduced Ejection Fraction: Model
Derivation and External Validation.
AB - BACKGROUND: Outpatients with heart failure (HF) who are at high risk for HF
hospitalization and death may benefit from early identification. We sought to
develop and externally validate a model to predict both HF hospitalization and
mortality that accounts for the semicompeting nature of the 2 outcomes and
captures the risk associated with the transition from the stable outpatient state
to the post-HF hospitalization state. METHODS AND RESULTS: A multistate model to
predict HF hospitalization and all-cause mortality was derived using data
(n=3834) from the HEAAL study (Heart Failure Endpoint evaluation of Angiotensin
II Antagonist Losartan), a multinational randomized trial in symptomatic patients
with reduced left ventricular ejection fraction. Twelve easily and reliably
obtainable demographic and clinical predictors were prespecified for model
inclusion. Model performance was assessed in the SCD-HeFT cohort (Sudden Cardiac
Death in Heart Failure Trial; n=2521). At 1 year, the probability of being alive
without HF hospitalization was 94% for a typical patient in the lowest risk
quintile and 77% for a typical patient in the highest risk quintile and this
variability in risk continued through 7 years of follow-up. The model c-index was
0.72 in the derivation cohort, 0.66 in the validation cohort, and 0.69 in the
implantable cardiac defibrillator arm of the validation cohort. There was
excellent calibration across quintiles of predicted risk. CONCLUSIONS: Our
findings illustrate the advantages of a multistate modeling approach, providing
estimates of HF hospitalization and death in the same model, comparison of
predictors for the different outcomes and demonstrating the different
trajectories of patients based on baseline characteristics and intermediary
events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
identifiers: NCT00000609 and NCT00090259.
PMID- 27514753
TI - Tetramethylpyrazine Ameliorates Rotenone-Induced Parkinson's Disease in Rats:
Involvement of Its Anti-Inflammatory and Anti-Apoptotic Actions.
AB - Parkinson's disease (PD) is a slowly progressive neurodegenerative movement
disorder. Apoptosis, neuroinflammation, and oxidative stress are the current
hypothesized mechanisms for PD pathogenesis. Tetramethylpyrazine (TMP), the major
bioactive component of Ligusticum wallichii Franchat (ChuanXiong), Family
Apiaceae, reportedly has anti-apoptotic, anti-inflammatory and antioxidant
effects. This study investigated the role of 'TMP' in preventing rotenone-induced
neurobiological and behavioral sequelae. A preliminary dose-response study was
conducted where rats received TMP (10, 20, and 40 mg/kg, i.p.) concomitantly with
rotenone (2 mg/kg, s.c.) for 4 weeks. Catalepsy, locomotor activity, striatal
dopamine content, and tyrosine hydroxylase "TH" and alpha-synuclein
immunoreactivity were evaluated. The selected TMP dose (20 mg/kg) was used for
western blot analysis of Bax, Bcl2, and DJ-1, immunohistochemical detection of
nuclear factor kappa B (NF-kB), inducible nitric oxide synthase (iNOS),
cyclooxygenase-2 (COX2), and glial fibrillary acidic protein (GFAP) expression,
in addition to biochemical analysis of caspase-3 activity, nuclear factor
erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) levels. Results
showed that TMP (20 mg/kg) significantly improved midbrain and striatal TH
expression and striatal dopamine content as well as the motor deficits, compared
to rotenone-treated group. These results were correlated with reduction in
caspase-3 activity and alpha-synuclein expression, along with improvement of
midbrain and striatal Bax/Bcl2 ratio compared to rotenone-treated group. TMP also
attenuated rotenone-induced upregulation of Nrf2/HO-1 pathway. Furthermore, TMP
downregulated rotenone-induced neuroinflammation markers: NF-kB, iNOS, COX2, and
GFAP expression in both the midbrain and striatum. Taken together, the current
study suggests that TMP is entitled to, at least partially, preventing PD
neurobiological and behavioral deficits by virtue of its anti-apoptotic, anti
inflammatory, and antioxidant actions.
PMID- 27514754
TI - Phenotypical and Pharmacological Characterization of Stem-Like Cells in Human
Pituitary Adenomas.
AB - The presence and functional role of tumor stem cells in benign tumors, and in
human pituitary adenomas in particular, is a debated issue that still lacks a
definitive formal demonstration. Fifty-six surgical specimens of human pituitary
adenomas were processed to establish tumor stem-like cultures by selection and
expansion in stem cell-permissive medium or isolating CD133-expressing cells.
Phenotypic and functional characterization of these cells was performed (1) ex
vivo, by immunohistochemistry analysis on paraffin-embedded tissues; (2) in
vitro, attesting marker expression, proliferation, self-renewal, differentiation,
and drug sensitivity; and (3) in vivo, using a zebrafish model. Within pituitary
adenomas, we identified rare cell populations expressing stem cell markers but
not pituitary hormones; we isolated and expanded in vitro these cells, obtaining
fibroblast-free, stem-like cultures from 38 pituitary adenoma samples. These
cells grow as spheroids, express stem cell markers (Oct4, Sox2, CD133, and
nestin), show sustained in vitro proliferation as compared to primary cultures of
differentiated pituitary adenoma cells, and are able to differentiate in hormone
expressing pituitary cells. Besides, pituisphere cells, apparently not
tumorigenic in mice, engrafted in zebrafish embryos, inducing pro-angiogenic and
invasive responses. Finally, pituitary adenoma stem-like cells express regulatory
pituitary receptors (D2R, SSTR2, and SSTR5), whose activation by a
dopamine/somatostatin chimeric agonist exerts antiproliferative effects. In
conclusion, we provide evidence that human pituitary adenomas contain a
subpopulation fulfilling biological and phenotypical signatures of tumor stem
cells that may represent novel therapeutic targets for therapy-resistant tumors.
PMID- 27514755
TI - Autophagy Inhibition Favors Survival of Rubrospinal Neurons After Spinal Cord
Hemisection.
AB - Spinal cord injuries (SCIs) are devastating conditions of the central nervous
system (CNS) for which there are no restorative therapies. Neuronal death at the
primary lesion site and in remote regions that are functionally connected to it
is one of the major contributors to neurological deficits following
SCI.Disruption of autophagic flux induces neuronal death in many CNS injuries,
but its mechanism and relationship with remote cell death after SCI are unknown.
We examined the function and effects of the modulation of autophagy on the fate
of axotomized rubrospinal neurons in a rat model of spinal cord dorsal
hemisection (SCH) at the cervical level. Following SCH, we observed an
accumulation of LC3-positive autophagosomes (APs) in the axotomized neurons 1 and
5 days after injury. Furthermore, this accumulation was not attributed to greater
initiation of autophagy but was caused by a decrease in AP clearance, as
demonstrated by the build-up of p62, a widely used marker of the induction of
autophagy. In axotomized rubrospinal neurons, the disruption of autophagic flux
correlated strongly with remote neuronal death and worse functional recovery.
Inhibition of AP biogenesis by 3-methyladenine (3-MA) significantly attenuated
remote degeneration and improved spontaneous functional recovery, consistent with
the detrimental effects of autophagy in remote damage after SCH. Collectively,
our results demonstrate that autophagic flux is blocked in axotomized neurons on
SCI and that the inhibition of AP formation improves their survival. Thus,
autophagy is a promising target for the development of therapeutic interventions
in the treatment of SCIs.
PMID- 27514756
TI - Adiponectin Suppresses T Helper 17 Cell Differentiation and Limits Autoimmune CNS
Inflammation via the SIRT1/PPARgamma/RORgammat Pathway.
AB - T helper 17 (Th17) cells are vital components of the adaptive immune system
involved in the pathogenesis of most autoimmune and inflammatory syndromes, and
adiponectin(ADN) is correlated with inflammatory diseases such as multiple
sclerosis (MS) and type II diabetes. However, the regulatory effects of
adiponectin on pathogenic Th17 cell and Th17-mediated autoimmune central nervous
system (CNS) inflammation are not fully understood. In this study, we
demonstrated that ADN could inhibit Th1 and Th17 but not Th2 cells
differentiation in vitro. In the in vivo study, we demonstrated that ADN
deficiency promoted CNS inflammation and demyelination and exacerbated
experimental autoimmune encephalomyelitis (EAE), an animal model of human MS.
Furthermore, ADN deficiency increased the Th1 and Th17 cell cytokines of both the
peripheral immune system and CNS in mice suffering from EAE. It is worth
mentioning that ADN deficiency predominantly promoted the antigen-specific Th17
cells response in autoimmune encephalomyelitis. In addition, in vitro and in
vivo, ADN upregulated sirtuin 1 (SIRT1) and peroxisome proliferator-activated
receptor gamma (PPARgamma) and inhibited retinoid-related orphan receptor-gammat
(RORgammat); the key transcription factor during Th17 cell differentiation. These
results systematically uncovered the role and mechanism of adiponectin on
pathogenic Th17 cells and suggested that adiponectin could inhibit Th17 cell
mediated autoimmune CNS inflammation.
PMID- 27514758
TI - Childhood cognitive ability and smoking initiation, relapse and cessation
throughout adulthood: evidence from two British cohort studies.
AB - AIMS: To test the relationship between early cognitive ability and major changes
in smoking habits across adulthood, and test whether educational attainment
mediates these associations. DESIGN: Prospective observational study to examine
the link between cognitive ability and smoking initiation, relapse and cessation
at multiple time-points throughout adulthood in a pooled analysis of two cohorts.
SETTING: Great Britain 1981-2013. PARTICIPANTS: A total of 16 653 participants
from two British cohorts; 7191 from the 1970 British Cohort Study (BCS) and 9462
from the 1958 National Child Development Study (NCDS). Participants were 52.9%
female and 27.3% were smokers, 24.8% were ex-smokers and 47.9% reported never
smoking. MEASUREMENTS: Cognitive ability was assessed at age 10 years in the BCS
and 11 years in the NCDS. Outcomes were smoking initiation, relapse and cessation
derived from changes in smoking status observed across five time-points between
ages 26-42 in the BCS and six time-points between ages 23-55 in the NCDS.
Educational attainment was examined as a mediating variable. Controls were age,
gender, social class, self-control, psychological distress, parental smoking and
a study indicator (BCS/NCDS). FINDINGS: In adjusted regression models, a 1
standard deviation increase in cognitive ability predicted a 0.5 percentage point
(95% CI = -0.9 to -0.1) reduced probability of smoking and a 2.9 percentage point
(95% CI = 2.1-3.7) higher probability of smoking cessation throughout adulthood,
but did not change the likelihood of smoking relapse significantly. Differences
in educational attainment explained approximately half the association between
childhood cognitive ability and smoking initiation/cessation. CONCLUSIONS: Lower
cognitive ability, measured in childhood before smoking is initiated, appears to
predict a higher likelihood of taking up smoking and a lower likelihood of
quitting in adulthood. Educational attainment appears to mediate this effect:
children with higher cognitive ability tend to become more highly educated adults
which, in turn, predicts lower rates of smoking initiation and increased rates of
smoking cessation.
PMID- 27514757
TI - Specificity of Pitx3-Dependent Gene Regulatory Networks in Subsets of Midbrain
Dopamine Neurons.
AB - Dysfunction of midbrain dopaminergic (mDA) neurons is involved in Parkinson's
disease (PD) and neuropsychiatric disorders. Pitx3 is expressed in mDA neuron
subsets of the substantia nigra compacta (SNc) and of the ventral tegmental area
(VTA) that are degeneration-sensitive in PD. The genetic network(s) and mode(s)
of action of Pitx3 in these mDA neurons remain poorly characterized. We
hypothesized that, given their distinct neuronal identities, Pitx3-expressing
neurons of SNc and VTA should differ in their Pitx3-controlled gene expression
networks and this may involve subset-specific co-regulators. Expression profiling
of purified mDA neuronal subsets indicates that Pitx3 regulates different sets of
genes in SNc and VTA, such as activating the expression of primary cilium gene
products specifically in VTA neurons. Interaction network analysis pointed to the
participation of differentially expressed Lhx/Lmo family members in the
modulation of Pitx3 action in SNc and VTA mDA neurons. Conversely, global binding
patterns of Pitx3 on genomic DNA of human dopaminergic cells revealed that Pitx3
is often co-recruited to regions that foster the formation of GATA-bHLH-BRN
complexes, which usually involve Lmo co-regulatory proteins. We focused on Lmo3
for its preferential expression in SNc neurons and demonstrated that it functions
as a transcriptional co-activator of Pitx3 by enhancing its activity on genomic
regulatory elements. In summary, we defined the SN and VTA-specific programs of
Pitx3-dependent gene expression and identified Lmo3 as a SN-specific co-regulator
of Pitx3-dependent transcription.
PMID- 27514759
TI - Weight loss induced by bariatric surgery restores adipose tissue PNPLA3
expression.
AB - BACKGROUND & AIMS: Obesity and its related co-morbidities such as non-alcoholic
fatty liver disease (NAFLD) are increasing dramatically worldwide. The genetic
variation in Patatin-like phospholipase domain-containing protein 3 (PNPLA3),
which is also called adiponutrin (ADPN), in residue 148 (I148M, rs738409) has
been associated with NAFLD. However, the regulation and function of PNPLA3 in
metabolic diseases remains unclear. Laparoscopic gastric banding (LAGB) of
severely obese patients reduces body weight, liver and adipose tissue
inflammation. In this study, we investigated whether weight loss induced by LAGB
affected PNPLA3 expression in hepatic and adipose tissue. METHODS: Liver and
subcutaneous adipose tissue samples were collected from 28 severely obese
patients before and 6 months after LAGB. PNPLA3 expression was assessed by
quantitative real-time PCR. To understand whether inflammatory stimuli regulated
PNPLA3 expression, we studied the effect of tumour necrosis factor alpha
(TNFalpha) and lipopolysaccharide (LPS) on PNPLA3 expression in human adipocytes
and hepatocytes. RESULTS: PNPLA3 was strongly expressed in the liver and clearly
detectable in subcutaneous adipose tissue of obese patients. Weight loss induced
by LAGB of severely obese patients led to significantly increased adipose, but
not hepatic, tissue expression of PNPLA3. Subcutaneous PNPLA3 expression
negatively correlated with body-mass-index, fasting glucose and fasting insulin.
TNFalpha potently suppressed PNPLA3 expression in adipocytes but not hepatocytes.
CONCLUSIONS: Weight loss induced by LAGB restored adipose tissue PNPLA3
expression which is suppressed by TNFalpha. Further studies will be required to
determine the functional impact of PNPLA3 and its related genetic variation on
adipose tissue inflammation and NAFLD.
PMID- 27514760
TI - Enhanced Structural Stability and Photo Responsiveness of CH3 NH3 SnI3 Perovskite
via Pressure-Induced Amorphization and Recrystallization.
AB - An organic-inorganic halide CH3 NH3 SnI3 perovskite with significantly improved
structural stability is obtained via pressure-induced amorphization and
recrystallization. In situ high-pressure resistance measurements reveal an
increased electrical conductivity by 300% in the pressure-treated perovskite.
Photocurrent measurements also reveal a substantial enhancement in visible-light
responsiveness. The mechanism underlying the enhanced properties is shown to be
associated with the pressure-induced structural modification.
PMID- 27514761
TI - Onconephrology: What Should the Internist Know About Targeted Therapy in Solid
Tumors?
AB - Advances in medical oncology has led cancer patients to live longer. Moreover,
the field of molecular oncology is rapidly evolving, new therapies emerge, and
drugs are approved quickly. This has led nephrologists to encounter new and
partially unrecognized treatments of the targeted therapy agents with kidney
adverse effects. These agents fall mainly into 2 categories affecting the
vascular endothelial growth factor and endothelial growth factor pathways. This
review covers the incidence of kidney disease induced by these agents,
pathophysiologic mechanisms, and clinical presentation, and is the first to
recommend an adequate management for each pathophysiology.
PMID- 27514762
TI - Spontaneous Hemorrhage in a Renal Abscess Mimicking Renal Neoplasm.
PMID- 27514763
TI - Influence of Fluid Balance on Morbidity and Mortality in Critically Ill Patients
With Acute Kidney Injury.
AB - INTRODUCTION: Fluid management in critically ill patients with acute kidney
injury (AKI) is controversial. Our study is aimed to evaluate the association
between fluid balance and patient outcome in AKI patients admitted to intensive
care unit (ICU). MATERIALS AND METHODS: This prospective study was carried out at
Lilavati Hospital and Research Centre on 130 critically ill patients with AKI
admitted to ICU. Mean daily fluid balance (MDFB) was measured and its correlation
with clinical characteristics and outcomes was assessed. RESULTS: During ICU
stay, 48.2% patients had a positive and 52.8% had a negative MDFB. In the
patients with positive MDFB, mean ICU stay was longer and ventilation
requirement, duration of ventilation, inotrope requirement, and duration of
inotrope were greater as compared to the group with negative MDFB. A
significantly higher mortality rate were observed in the patients with positive
MDFB as compared to negative MDFB (43.5% versus 7.4%). CONCLUSIONS: Negative
fluid balance was independently associated with a significant reduction in
mortality, ICU stay, ventilator requirement, and the need for renal replacement
among critically ill patients with AKI.
PMID- 27514764
TI - Renoprotective Effect of Plantago Major Against Nephrotoxicity and Oxidative
Stress Induced by Cisplatin.
AB - INTRODUCTION: The aim of this study was to investigate the possible
renoprotective effect of Plantago major extract against cisplatin-induced
nephrotoxicity in rats. MATERIALS AND METHODS: Rats were divided into 6 groups.
The first group was the control, group 2 was treated with cisplatin (7 mg/kg,
single dose), and groups 3 to 6 received cisplatin with vitamin E (100 mg/kg) and
Plantago major extract at doses of 300 mg/kg, 600 mg/kg, and 1200 mg/kg, for 20
days. RESULTS: On day12, serum concentration of urea, creatinine, and potassium
significantly increased and sodium concentration significantly decreased in the
cisplatin group compared with the control rats. However, serum creatinine, urea,
and potassium concentrations were significantly lower in all of the Plantago
major groups compared to the cisplatin group. Also, there was a significant
elevation in serum sodium concentration in the Plantago major 600 mg/kg group
compared to the cisplatin group on day12. Injection of cisplatin caused a
significant elevation in malondialdehyde concentration but a significant decrease
in catalase activity and total thiol content compared to the control group.
Plantago major extract at 1200 mg/kg significantly improved malondialdehyde
concentration and total thiol content compared to the cisplatin group. Catalase
activity with Plantago major significantly increased at all doses compared to the
cisplatin group. CONCLUSIONS: The current study suggests that Plantago major
extract and vitamin E are able to improve kidney function as well as oxidative
stress in cisplatin-induced renal toxicity in the rat.
PMID- 27514765
TI - Protective Effects of Hydroalcoholic Extract of Ferulago Angulata Against
Gentamicin-induced Nephrotoxicity in Rats.
AB - INTRODUCTION: Gentamicin can lead to acute tubular injury and kidney dysfunction.
This study aimed to evaluate the effect of Ferulago angulata on kidney function
and other markers in rats with gentamicin-induced nephrotoxicity. MATERIALS AND
METHODS: Forty-eight male Wistar rats were divided into the following groups:
group 1, the controls; group 2, rats receiving gentamicin (120 mg/kg body weight
per day, intraperitoneal) for 7 days without treatment; groups 3, 4 and 5, rats
receiving gentamicin for 7 days and oral treatment with 200 mg/kg, 400 mg/kg, and
800 mg/kg body weight per day of Ferulago angulate extract, respectively.
Measurements included serum levels of creatinine, urea, uric acid, lipids, ferric
reducing antioxidant power, and protein carbonyl; kidney and serum levels of
malondialdehyde; and serum and renal levels of tumor necrosis factor-alpha.
Histopathology of kidney tissue was examined as well as renal catalase,
superoxide dismutase, and vitamin C. RESULTS: Compared to treatment with
gentamicin only, treatment with Ferulago angulata resulted in a significantly
higher high-density lipoprotein cholesterol, ferric-reducing antioxidant plasma,
renal catalase, superoxide dismutase, and vitamin C levels. It was also
associated with significantly lower serum levels of creatinine, urea, uric acid,
malondialdehyde, protein carbonyl, tumor necrosis factor-alpha, total
cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low
density lipoprotein cholesterol. Ferulago angulate was linked with a lower renal
gene expression of tumor necrosis factor-alpha. CONCLUSIONS: The present study
suggests that Ferulago angulate extract has protective effects against
nephrotoxicity due to gentamicin.
PMID- 27514766
TI - Effects of Omega-3 Fatty Acid Supplementation on Inflammatory Cytokines and
Advanced Glycation End Products in Patients With Diabetic Nephropathy: a
Randomized Controlled Trial.
AB - INTRODUCTION: This study was performed to evaluate the effects of omega-3 fatty
acid supplementation on inflammatory cytokines and advanced glycation end
products (AGEs) in patients with diabetic nephropathy (DN). MATERIALS AND
METHODS: This randomized double-blind placebo-controlled trial was done on 60
patients with DN who were randomly divided into 2 groups to receive either 1000
mg/d of omega-3 fatty acid from flaxseed oil (n = 30) or placebo (n = 30) for 12
weeks. The primary outcome variables were tumor necrosis factor-alpha, receptor
tumor necrosis factor-alpha and growth differentiation factor 15. Fasting blood
samples were taken at the onset and the end of the study to quantify the related
markers. RESULTS: Compared with the placebo, omega-3 fatty acid supplementation
resulted in a significant decrease in serum AGEs (-2.3 +/- 2.8 AU versus 0.2 +/-
2.5 AU, P = .001). Despite a significant reduction in serum level of receptor for
AGEs (-0.1 +/- 0.3 AU, P = .02) in the omega-3 fatty acid group, no significant
difference was found between the two groups in terms of their effects on the
receptor for AGEs. Supplementation with omega-3 fatty acid had no significant
effect on the inflammatory cytokines as compared with the placebo. CONCLUSIONS:
Our study demonstrated that omega-3 fatty acid supplementation among DN patients
had favorable effects on AGEs and the receptor for AGEs.
PMID- 27514767
TI - Association Between 25-Hydroxyvitamin D Level and Inflammatory and Nutritional
Factors in Hemodialysis and Peritoneal dialysis Patients in Qom, Iran.
AB - INTRODUCTION: This study aimed to evaluate the prevalence of vitamin D inadequacy
in patients receiving maintenance hemodialysis and peritoneal dialysis (PD) and
its association with inflammatory and nutritional factors. MATERIALS AND METHODS:
A total of 176 hemodialysis and 32 PD patients participated in the study. Serum
levels of 25-hydroxyvitamin D, albumin, parathyroid hormone, calcium, phosphorus,
high-sensitivity C-reactive protein (HSCRP), and neutrophil-lymphocyte ratio
(NLR) were measured. Data on body mass index were also collected. Stepwise
multiple logistic regression analysis was used to identify predictors for 25
hydroxyvitamin D deficiency and its relationship with the nutritional and
inflammatory factors. RESULTS: No significant association was found between 25
hydroxyvitamin D and age, body mass index, serum calcium, serum phosphorus,
parathyroid hormone, serum albumin, dialysis quality, and duration of dialysis;
while NLR and HSCRP were significantly associated with 25-hydroxyvitamin D in the
hemodialysis patients only (P < .001 and P = .001, respectively). A positive
correlation was found between NLR and HSCRP in both hemodialysis and PD patients.
(r = 0.817; P < .001). This association was confirmed between an NLR greater than
3 and an HSCRP level greater than 3. CONCLUSIONS: Vitamin D deficiency was highly
prevalent in our dialysis patients, and inadequate level of vitamin D was
associated with inflammatory factors such as HSCRP and NLR in both hemodialysis
and PD patients. An easy and inexpensive test of an NLR greater than 3 could be
used as a measure of inflammation instead of HSCRP in both PD and hemodialysis
patients.
PMID- 27514768
TI - Zinc Supplementation in Treatment of Children With Urinary Tract Infection.
AB - INTRODUCTION: Urinary tract infection (UTI) is very common in children.
Precocious diagnosis and appropriate treatment are important because of the
permanent disease complications. Zinc increases the response to treatment in many
infections. In this study, we explored the effect of zinc in treating UTI.
MATERIALS AND METHODS: Two hundred children with UTI were divided into 2 groups
of 100 who were comparable in terms of age, sex, urine laboratory profiles, and
clinical signs and symptoms. The control group received a standard treatment
protocol for UTI and the intervention group received oral zinc sulfate syrup plus
routine treatment of UTI. RESULTS: A faster recovery was observed in the patients
receiving zinc, but abdominal pain was exacerbated by zinc and lasted longer.
Three months after the treatment, there was no significant difference between the
two groups in the time of fever stop and negative urine culture. CONCLUSIONS: In
children with UTI, zinc supplementation has a positive effect in ameliorating
severe dysuria and urinary frequency while the use of this medication is not
recommended in the presence of abdominal pain.
PMID- 27514769
TI - Inflammation, Left Ventricular Hypertrophy, and Mortality in End-stage Renal
Disease.
AB - INTRODUCTION: The aim of this study was to evaluate ventricular geometry, its
relationship with the inflammatory markers, and mortality of patients with end
stage renal disease on peritoneal and hemodialysis treatment. MATERIALS AND
METHODS: We enrolled adult patients on long-term dialysis (hemodialysis and
peritoneal dialysis) for more than 3 months. Two-dimensional echocardiography was
performed by an experienced cardiologist who was blinded to all clinical details
of patients. Cardiovascular mortality was assessed during a 2-year follow-up
period. RESULTS: There were 129 participants, of whom 86 (66%) were on
hemodialysis. Left ventricular hypertrophy was present in 86.7%; concentric
hypertrophy was found in 64 (49.1%) and eccentric hypertrophy in 48 patients
(37.2%). Patients with left ventricular hypertrophy were further divided into
tertiles according to their left ventricular mass index. Logistic regression
found pulse pressure as an independent risk factor associated with left
ventricular mass index (odds ratio [OR], 1.04; 95% confidence interval (CI), 1.01
to 1.19; P = .047). Cardiovascular mortality rate was 15.5%. Multivariable
analysis showed that C-reactive protein (OR, 1.06; 95% CI, 1.01 to 1.10; P =
.01), pulse pressure (OR, 1.01; 95% CI, 1.0 to 1.26; P = .046), and left
ventricular mass index (OR, 1.03; 95% CI, 1.01 to 1.21; P = .03) were independent
risk factors for cardiovascular mortality. CONCLUSIONS: Concentric hypertrophy is
the most frequent left ventricular geometry model in patients with chronic kidney
disease. Inflammation, pulse pressure, and left ventricular hypertrophy are
interrelated and all contribute to mortality and cardiovascular death risk among
dialysis patients.
PMID- 27514770
TI - Assessment of Circannual Rhythm in Plasma Level of Vitamin D Among Kidney
Transplant Recipients in Mashhad.
AB - We studied plasma vitamin D level in 96 kidney transplant recipients and its
circannual rhythm. Blood samples were tested for 25-hydroxy vitamin D,
parathyroid hormone, creatinine, phosphate, and calcium levels in winter and
summer 2014. The mean age was 41 years, and the mean transplant age was 6.1
years. Plasma levels of 25-hydroxy vitamin D were 18.0 +/- 15.0 ng/mL in winter
and 18.3 +/- 14.7 ng/mL in summer (P = .64). Parathyroid hormone was inversely
correlated with vitamin D level in both seasons (r = -0.044, P < .001). There was
no relationship between vitamin D and other variables. Our study showed vitamin D
deficiency is prevalent among kidney transplant recipients both in winter and
summer. Also, vitamin D level did not rise from winter to summer. It is
recommended to routinely check on kidney transplant recipients' vitamin D status.
PMID- 27514771
TI - Amyloidosis as a Renal Complication of Chronic Granulomatous Disease.
AB - Chronic granulomatous disease is a rare primary immunodeficiency disorder, which
leads to increased susceptibility to recurrent infections and severe inflammatory
manifestations. There have been reports regarding different aspects of
genitourinary involvement in chronic granulomatous disease, some of which are
hydronephrosis, granulomatous cystitis, and glomerulonephritis, but among these
complications, amyloidosis is rather rare. We report a patient with chronic
granulomatous disease that developed amyloidosis later in the course of the
disease.
PMID- 27514772
TI - Esophageal Perforation in a Patient With Kidney Transplantation.
AB - Esophageal perforation is a rupture of the esophageal wall, caused by
iatrogenesis in 56% of cases. Perforation of the esophagus remains a challenge,
and its incidence has increased as the use of endoscopic procedures has become
more frequent. We report a 54-year-old woman with esophageal perforation 8 days
after kidney transplantation. She had received a gastrointestinal consultation
prior to her transplantation. This report highlights the fact that perforation
may occur after any organ transplantation, especially during the initial 2 weeks
after transplantation, when mycophenolate mofetil and cyclosporine as well as and
high doses of corticosteroid are administered. If there is a delay in passage and
a swallowing difficulty, high doses of immunosuppressive drugs are likely to
cause ulceration and perforation. Preventive strategies including intravenous
steroids for the first 2 to 3 weeks and divided doses of pills should be
considered for such patients.
PMID- 27514773
TI - Anti-cancer synergy of dichloroacetate and EGFR tyrosine kinase inhibitors in
NSCLC cell lines.
AB - Glycolysis has been observed as a predominant process for most cancer cells to
utilize glucose, which was referred to as "Warburg Effect". Targeting critical
enzymes, such as pyruvate dehydrogenase kinase (PDK) that inversely regulating
the process of glycolysis could be a promising approach to work alone or in
combination with other treatments for cancer therapy. EGFR inhibitors for Non
Small-Cell Lung Cancer (NSCLC) treatment have been applied for decades in
clinical practices with great success, but also their clinical benefits were
somewhat hampered by the rising acquired-resistance. Combination drug therapy is
an effective strategy to cope with the challenge. In this study, we utilized
Dichloroacetate (DCA), a widely regarded PDK inhibitor, together with Erlotinib
and Gefitinib, two well-known EGFR inhibitors, and demonstrated that the
applications of DCA in combination with either Erlotinib or Gefitinib
significantly attenuated the viability of EGFR mutant NSCLC cells (NCI-H1975 and
NCI-H1650) in a synergistic manner. This synergistic outcome appears to be a
combination effect in promoting apoptosis, rather than co-suppression of either
EGFR or PDK signaling pathways. Moreover, we have shown that the combination
treatment did not exhibit synergistic effect in other NSCLC cell lines without
EGFR mutations (A549 or NCI-H460). Together, these observations suggested that
combined targeting of EGFR and PDK in NSCLC cells exerted synergistic effects in
an EGFR mutation-dependent fashion.
PMID- 27514774
TI - Individual personality differences in goats predict their performance in visual
learning and non-associative cognitive tasks.
AB - Variation in common personality traits, such as boldness or exploration, is often
associated with risk-reward trade-offs and behavioural flexibility. To date, only
a few studies have examined the effects of consistent behavioural traits on both
learning and cognition. We investigated whether certain personality traits
('exploration' and 'sociability') of individuals were related to cognitive
performance, learning flexibility and learning style in a social ungulate
species, the goat (Capra hircus). We also investigated whether a preference for
feature cues rather than impaired learning abilities can explain performance
variation in a visual discrimination task. We found that personality scores were
consistent across time and context. Less explorative goats performed better in a
non-associative cognitive task, in which subjects had to follow the trajectory of
a hidden object (i.e. testing their ability for object permanence). We also found
that less sociable subjects performed better compared to more sociable goats in a
visual discrimination task. Good visual learning performance was associated with
a preference for feature cues, indicating personality-dependent learning
strategies in goats. Our results suggest that personality traits predict the
outcome in visual discrimination and non-associative cognitive tasks in goats and
that impaired performance in a visual discrimination tasks does not necessarily
imply impaired learning capacities, but rather can be explained by a varying
preference for feature cues.
PMID- 27514775
TI - Quantification of Cancer Biomarkers in Serum Using Scattering-Based Quantitative
Single Particle Intensity Measurement with a Dark-Field Microscope.
AB - In this work, we developed a simple yet robust single particle scattering
intensity measurement method for the quantification of cancer-related biomarkers.
The design is based on the plasmonic coupling effect between noble metal
nanoparticles. First, the primary and secondary antibodies were conjugated onto
the surface of 60 nm gold nanoparticles (AuNPs, act as capture probes) and 50 nm
silver nanoparticles (AgNPs, act as signal amplification probes) respectively. In
the presence of corresponding antigen, a sandwiched immunocomplex was formed,
resulting a significantly enhanced scattering intensity in contrast to that of
individual probes. By measuring the intensity change of the particles with a dark
field microscope (DFM), the amount of target protein could be accurately
quantified. As a proof of concept experiment, quantification of three types of
antigens, including carcinoembryonic antigen (CEA), prostate-specific antigen
(PSA) and alpha fetoprotein (AFP) by this platform was demonstrated with limit of
detection (LOD) of 1.7, 3.3, and 5.9 pM, respectively, with a linear dynamic
range of 0 to 300 pM. Furthermore, to elucidate the potential in clinical
application, the content of antigens in a serum sample was also quantified
directly without additional sample pretreatment. In order to validate the
reliability of this method, the measured result was also compared with that
obtained by regular enzyme-linked immunosorbent assay (ELISA) kit, showing good
consistency between these two data sets. Therefore, owing to the simplicity and
accuracy of this method, it could be potentially applied for massive disease
screening in clinical assay in the future.
PMID- 27514776
TI - Potassium-competitive acid blockers: Advanced therapeutic option for acid-related
diseases.
AB - Acid-related diseases (ARDs), such as peptic ulcers and gastroesophageal reflux
disease, represent a major health-care concern. Some major milestones in our
understanding of gastric acid secretion and ARD treatment reached during the last
50years include 1) discovery of histamine H2-receptors and development of H2
receptor antagonists, 2) identification of H+,K+-ATPase as the parietal cell
proton pump and development of proton pump inhibitors (PPIs), and 3)
identification of Helicobacter pylori (H. pylori) as the major cause of peptic
ulcers and development of effective eradication regimens. Although PPI treatments
have been effective and successful, there are limitations to their efficacy and
usage, i.e. short half-life, insufficient acid suppression, slow onset of action,
and large variation in efficacy among patients due to CYP2C19 metabolism.
Potassium-competitive acid blockers (P-CABs) inhibit H+,K+-ATPase in a reversible
and K+-competitive manner, and exhibit almost complete inhibition of gastric acid
secretion from the first dose. Many pharmaceutical companies have tried to
develop P-CABs, but most of their clinical development has been discontinued due
to safety concerns or a similar efficacy to PPIs. Revaprazan was developed in
Korea and was the first P-CAB approved for sale. Vonoprazan, approved in 2014 in
Japan, has a completely different chemical structure and higher pKa value
compared to other P-CABs, and exhibits rapid onset of action and prolonged
control of intragastric acidity. Vonoprazan is an effective treatment for ARDs
that is especially effective in healing reflux esophagitis and for H. pylori
eradication. P-CABs, such as vonoprazan, promise to further improve the
management of ARDs.
PMID- 27514777
TI - The influence of trematode parasite burden on gene expression in a mammalian
host.
AB - BACKGROUND: Parasites can profoundly impact their hosts and are responsible for a
plethora of debilitating diseases. To identify global changes in host gene
expression related to parasite infection, we sequenced, assembled, and annotated
the liver transcriptomes of Balb/cj mice infected with the trematode parasite
Schistosoma mansoni and compared the results to uninfected mice. We used two
different methodologies (i.e. de novo and reference guided) to evaluate the
influence of parasite sequences on host transcriptome assembly. RESULTS: Our
results demonstrate that the choice of assembly methodology significantly
impacted the proportion of parasitic reads detected from the host library, yet
the presence of non-target (xenobiotic) sequences did not create significant
structural errors in the assembly. After removing parasite sequences from the
mouse transcriptomes, we analyzed host gene expression under different parasite
infection levels and observed significant differences in the associated
immunologic and metabolic responses based on infection level. In particular,
genes associated with T-helper type 1 (Th-1) and T-helper type 2 (Th-2) were up
regulated in infected mice whereas genes related to amino acid and carbohydrate
metabolism were down-regulated in infected mice. These changes in gene expression
scale with infection status and likely impact the evolutionary fitness of hosts.
CONCLUSIONS: Overall, our data indicate that a) infected mice reduce the
expression of key metabolic genes in direct proportion to their infection level;
b) infected mice similarly increase the expression of key immune genes in
response to infection; c) patterns of gene expression correspond to the
pathological symptoms of schistosomiasis; and d) identifying and filtering out
non-target sequences (xenobiotics) improves differential expression prediction.
Our findings identify parasite targets for RNAi or other therapies and provide a
better understanding of the pathology and host immune repertoire involved in
response to S. mansoni infections.
PMID- 27514778
TI - Implementation of a clinical practice guideline for schizophrenia in a specialist
mental health center: an observational study.
AB - BACKGROUND: In mental health settings, implementation of and adherence to
clinical practice guidelines (CPGs) is low. Strategies are needed to overcome
barriers and facilitate successful implementation of CPGs into standard care. The
goals of this study were to develop a framework for the implementation of a CPG
for schizophrenia for hospitalized service users in a mental health care
facility, and to monitor adherence to the guideline. METHODS: An eight-step
framework was developed based on project management principles: 1) the Appraisal
Guideline for Research and Evaluation (AGREE) tool was used to rate and select a
CPG; 2) an algorithm was created from the guideline; 3) a gap analysis identified
clinical services and processes not conforming with the CPG recommendations; 4) a
governance structure was created; 5) a modified Delphi process determined key
outcome and process adherence metrics; 6) a project charter was developed; 7)
clinical informatics ensured that systems and tools were in place to support the
CPG; and 8) therapeutic services were realigned to match the requirements of the
CPG within specified fiscal constraints. Percent adherence to the identified
process adherence metrics was calculated before (March 2014) and for 12 months
after implementation (April 2014-March 2015). RESULTS: The National Institute of
Health and Care Excellence guideline scored highest on AGREE and was used to
develop the algorithm. Cognitive behavior therapy for psychosis (CBT-P), art
therapy and carer assessments were identified as gaps in care. Clinical global
impression - Schizophrenia score was identified as the primary service user
outcome variable and antipsychotic polypharmacy, metabolic monitoring, CBT-P
referral and supported employment/vocational services referral as the primary
process adherence measures. Adherence to guidance for metabolic monitoring (March
2014, 76.7 %; March 2015, 81.6 %), CBT-P referral (March 2014, 6.5 %; March 2015,
11.4 %) and vocational rehabilitation referral (March 2014, 36.6 %; March 2015,
49.1 %) were increased after CPG implementation. There was an initial increase in
adherence to antipsychotic monotherapy (March 2014, 53.4 %; November 2014, 62.7
%), which decreased back toward baseline (March 2015, 55.1 %). CONCLUSIONS: The
eight-step framework was used to implement a CPG process, though further quality
improvements initiatives may be needed to improve adherence.
PMID- 27514779
TI - Evaluation of hypercoagulability state in perinatal arterial ischemic stroke with
rotation thromboelastometry.
AB - BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is an important cause of
pediatric morbidity and mortality. The etiology of PAIS remains unknown. Several
maternal-neonatal disorders, and especially prothrombotic risk factors, have been
reported in infants with perinatal stroke (PS). Rotation thromboelastometry
(ROTEM) can analyze the coagulation system, from the beginning of coagulation,
through clot formation, and ending with fibrinolysis. The aim of this study was
to evaluate the hypercoagulability state in PAIS patients using ROTEM. METHODS:
Patients were obtained by evaluating hospital files retrospectively. Twenty
patients with PAIS and 19 healthy controls were included in the study.
Prothrombotic risk factors and standard coagulation parameters were collected for
all patients. Thromboelastometry (TEM) analysis was performed with the ROTEM(r)
Coagulation Analyzer model Gamma 2500 (Tem International, Munich, Germany).
Patients were separated into two groups; Group 1 included PAIS patients with
prothrombotic risk factors and Group 2 included patients with no prothrombotic
risk factors. RESULTS: Group 1 includes six patients and Group 2 includes
fourteen. Maternal risk factors were reported in 55 % and prothrombotic risk
factors were detected in 30 % of the patients. ROTEM analyses were done mean age
of 11.2 +/- 9.4 months. ROTEM analysis showed that maximum clot firmness (MCF)
value on both groups was significantly higher than in the control group, which is
consistent with a hypercoagulable state. There was no statistical difference
between the MCF values of Group 1 and Group 2. No significant correlations were
found between the ROTEM parameters and the hematological parameters. CONCLUSION:
The etiology of PAIS is still unclear. Prothrombotic risk factors may be an
important etiology for PAIS. However, standard hematological tests for evaluating
prothrombotic risk factors are limited. In our study, ROTEM analyses showed
higher maximum clot firmness in PAIS patients compared to controls. ROTEM
analyses may suggest a hypercoagulable state due to abnormal fibrinolysis in PAIS
patients. Normative data and further research is needed to validate our findings.
PMID- 27514780
TI - Cloning and characterization of tyrosine hydroxylase (TH) from the pacific white
leg shrimp Litopenaeus vannamei, and its expression following pathogen challenge
and hypothermal stress.
AB - Tyrosine hydroxylase (TH) belongs to the biopterin-dependent aromatic amino acid
hydroxylase enzyme family, and it represents the first and rate-limiting step in
the synthesis of catecholamines that are required for physiological and immune
process in invertebrates and vertebrates. Cloned Litopenaeus vannamei TH (LvTH),
containing a short alpha helix domain, a catalytic core, a regulatory domain, a
phosphorylation site and two potential N-linked glycosylation sites as presented
in vertebrate and insect THs without acidic region and signal peptide cleavage
sites at the amino-terminal, exhibited a similarity of 60.0-61.2% and 45.0-47.0%
to that of invertebrate and vertebrate THs, respectively. Further, LvTH
expression was abundant in gill and haemocytes determined by quantitative real
time PCR. L. vannamei challenged with Vibrio alginolyticus at 10(5) cfu shrimp(
1) revealed significant increase of LvTH mRNA expression in haemocytes within 30
120 min and in brain within 15-30 min followed with recuperation. In addition,
shrimps exposed to hypothermal stress at 18 degrees C significantly increased
LvTH expression in haemocytes and brain within 30-60 and 15-60 min, respectively.
The TH activity and haemolymph glucose level (haemocytes-free) significantly
increased in pathogen challenged shrimp at 120 min and 60 min, and in hypothermal
stressed shrimp at 30-60 and 30 min, respectively. These results affirm that
stress response initiates in the brain while haemocytes display later response.
Further, the significant elevation of TH activity in haemolymph is likely to
confer by TH that released from haemocytes. In conclusion, the cloned LvTH in our
current study is a neural TH enzyme appears to be involved in the physiological
and immune responses of whiteleg shrimp, L. vannamei suffering stressful
stimulation.
PMID- 27514781
TI - Identification and characterization of a novel Toll-like receptor 4 homologue in
blunt snout bream, Megalobrama amblycephala.
AB - Toll-like receptors (TLRs) are central players in the innate immune system in
response to a wide range of pathogen infection. Among various TLRs, TLR4 plays a
key role in recognition of bacterial lipopolysaccharides (LPS). In the present
study, we identified and characterized a novel TLR4 homologue (maTLR4b) in blunt
snout bream (Megalobrama amblycephala) which was significantly distinct from
previously reported M. amblycephala TLR4 (tentatively named maTLR4a). The results
showed that the complete cDNA sequence of maTLR4b was 3261 bp with an open
reading frame encoding a polypeptide of 820 amino acids, and that its genomic
sequence was 3793 bp, which had 3 exons. Structurally, the deduced maTLR4b
protein showed a typical TLR domain architecture, including a signal peptide,
eight leucine-rich repeats (LRRs) in the extracellular region, a transmembrane
domain, and a Toll-Interleukin 1 receptor (TIR) domain in the cytoplasmic region.
Phylogenetic analysis revealed that all TLR4s from teleost fish formed a
monophyletic clade. Both maTLR4a and maTLR4b were divided into two distinct
branches, and showed the highest level of similarity with the grass carp TLR4.2
and TLR4.4 homologue, respectively. MaTLR4b was constitutively expressed in all
healthy tissues tested although at different levels. After LPS stimulation, the
expression levels were significantly up-regulated in spleen, and peaked at 4 h
between maTLR4a and maTLR4b, but with a distinct and complementary expression
patterns. Taken together, these results suggested that maTLR4b is indeed a
functional homologue of TLR4 in other species, which may play vital role in
innate immune.
PMID- 27514782
TI - Evolutionary analysis of the jacalin-related lectin family genes in 11 fishes.
AB - Jacalin-related lectins are a type of carbohydrate-binding proteins, which are
distributed across a wide variety of organisms and involved in some important
biological processes. The evolution of this gene family in fishes is unknown.
Here, 47 putative jacalin genes in 11 fish species were identified and divided
into 4 groups through phylogenetic analysis. Conserved gene organization and
motif distribution existed in each group, suggesting their functional
conservation. Some fishes have eleven jacalin genes, while others have only one
or zero gene in their genomes, suggesting dynamic changes in the number of
jacalin genes during the evolution of fishes. Intragenic recombination played a
key role in the evolution of jacalin genes. Synteny analyses of jacalin genes in
some fishes implied conserved and dynamic evolution characteristics of this gene
family and related genome segments. Moreover, a few functional divergence sites
were identified within each group pairs. Divergent expression profiles of the
zebra fish jacalin genes were further investigated in different stresses. The
results provided a foundation for exploring the characterization of the jacalin
genes in fishes and will offer insights for additional functional studies.
PMID- 27514783
TI - Functional characterizations and expression profiles of ADAR2 gene, responsible
for RNA editing, in response to GCRV challenge in grass carp (Ctenopharyngodon
idella).
AB - ADAR (adenosine deaminases acting on RNA)-mediated adenosine-to-inosine (A-to-I)
editing to double-stranded RNA (dsRNA) is a critical arm of the antiviral
response. The present study focused on the structural and functional
characterizations of grass carp (Ctenopharyngodon idella) ADAR2 (CiADAR2) gene.
The complete genomic sequence of CiADAR2 is 150,458 bp in length, containing 12
exons and 11 introns. The open reading frame (ORF) of 2100 bp encodes a
polypeptide of 699 amino acids (aa) which contains three highly conservative
domains - two N-terminal dsRNA binding domains (dsRBDs) and one C-terminal
deaminase domain. The predicted crystal structure of CiADAR2 deaminase domain
suggested a catalytic center form in the enzyme active site. CiADAR2 mRNA was
ubiquitously expressed in the fifteen tested tissues, and was induced post GCRV
challenge in spleen and head kidney and C. idella kidney (CIK) cells. The ex vivo
expression of CiADAR2 protein was verified by the Flag (tag)-based western blot
assay. Antiviral activity assay of CiADAR2 was manifested by the delayed
appearance of cytopathic effect (CPE) and inhibition of GCRV yield at 48 h post
infection. Furthermore, in CiADAR2 overexpression cells, mRNA expression levels
of CiIFN1, CiTLR7 and CiTLR8 were facilitated at different time points after GCRV
infection, comparing to those in control group. Taken together, it was indicated
that ADAR2 was an antiviral cytokine against GCRV and anti-GCRV function
mechanism might involve in the TLR7/8-regulated IFN-signaling. These findings
suggested that CiADAR2 was a novel member engaging in antiviral innate immune
defense in C. idella, which laid a foundation for the further mechanism research
of ADAR2 in fishes.
PMID- 27514784
TI - Molecular structure and immune-stimulated transcriptional modulation of the first
teleostean IFP35 counterpart from rockfish (Sebastes schlegelii).
AB - Interferons (IFNs) and IFN-inducible proteins play numerous physiological roles,
particularly in antiviral defense mechanisms of the innate immune response with
the presence of pathogens. IFN-induced protein-35 kDa (IFP35) is induced by Type
II IFN (IFN-gamma); it is a cytoplasmic protein that can be translocated to the
nucleus via the stimulation of IFN. In this study, we report the complete
molecular characterization of the IFP35 cDNA sequence from the black rockfish in
an effort to understand its role in the immune response. The coding sequence of
RfIFP35 encoded a putative peptide of 371 amino acids containing two
characteristic Nmi/IFP 35 domains (NIDs), which are highly conserved among its
counterparts. The protein showed a molecular mass of 42.2 kDa with a theoretical
pI of 5.05 and was predicted to be unstable because of its high instability index
(49.37). Therefore, the protein-protein interaction is essential for its
stability, which may be facilitated by the intrinsically disordered regions in
this protein. According to cellular location prediction, the RfIFP35 protein is
cytosolic. Phylogenetic analysis showed that RfIFP35 was cladded within the fish
counterparts. Tissue distribution profiling revealed a ubiquitous presence of the
protein in all examined tissues, with highest expression in the blood followed by
the spleen tissues. The expression of RfIFP35 during immune challenge with poly
I:C and lipopolysaccharide treatments affirms its putative importance in the
first-line host defense system. RfIFN-gamma mRNA was significantly expressed at 6
h p.i. in blood and 3 h p.i. in the spleen following treatment with different
immune stimulants, and its expression was higher compared to that of RfIFP35
mRNA. Therefore, the modulation patterns of both RfIFP35 and RfIFN-gamma suggest
that RfIFP35 may be induced by RfIFN-gamma.
PMID- 27514785
TI - The protective effects of taurine on acute ammonia toxicity in grass carp
Ctenopharynodon idellus.
AB - The four experimental groups were carried out to test the response of grass carp
Ctenopharyngodon idella to ammonia toxicity and taurine: group 1 was injected
with NaCl, group 2 was injected with ammonium acetate, group 3 was injected with
ammonium acetate and taurine, and group 4 was injected taurine. Fish in group 2
had the highest ammonia content in the liver and brain, and alanine, arginine,
glutamine, glutamate and glycine contents in liver. Brain alanine and glutamate
of fish in group 2 were significantly higher than those of fish in group 1.
Malondialdehyde content of fish in group 2 was the highest, but superoxide
dismutase and glutathione activities were the lowest. Although fish in group 2
had the lowest red cell count and hemoglobin, the highest alkaline phosphatase,
complement C3, C4 and total immunoglobulin contents appeared in this group. In
addition, superoxide dismutase and glutathione activities, red cell count and
hemoglobin of fish in group 3 were significantly higher than those of fish in
group 2, but malondialdehyde content is the opposite. This study indicates that
ammonia exerts its toxic effects by interfering with amino acid transport,
inducing reactive oxygen species generation and malondialdehyde accumulation,
leading to blood deterioration and over-activation of immune response. The
exogenous taurine could mitigate the adverse effect of high ammonia level on fish
physiological disorder.
PMID- 27514786
TI - Dietary effects of adenosine monophosphate to enhance growth, digestibility,
innate immune responses and stress resistance of juvenile red sea bream, Pagrus
major.
AB - Our study explored the dietary effects of adenosine monophosphate (AMP) to
enhance growth, digestibility, innate immune responses and stress resistance of
juvenile red sea bream. A semi-purified basal diet supplemented with 0%
(Control), 0.1% (AMP-0.1), 0.2% (AMP-0.2), 0.4% (AMP-0.4) and 0.8% (AMP-0.8)
purified AMP to formulate five experimental diets. Each diet was randomly
allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days.
The results indicated that dietary AMP supplements tended to improve growth
performances. One of the best ones was found in diet group AMP-0.2, followed by
diet groups AMP-0.1, AMP-0.4 and AMP-0.8. The Apparent digestibility coefficients
(dry matter, protein and lipid) also improved by AMP supplementation and the
significantly highest dry matter digestibility was observed in diet group AMP
0.2. Fish fed diet groups AMP-0.2 and AMP-0.4 had significantly higher peroxidase
and bactericidal activities than fish fed the control diet. Nitro-blue
tetrazolium (NBT) activity was found to be significantly (P < 0.05) greater in
fish fed diet groups AMP-0.4 and AMP-0.8. Total serum protein, lysozyme activity
and agglutination antibody titer were also increased (P > 0.05) by dietary
supplementation. In contrast, catalase activity decreased with AMP
supplementation. Moreover, the fish fed AMP supplemented diets had better
improvement (P < 0.05) in body lipid contents, condition factor, hematocrit
content and glutamyl oxaloacetic transaminase (GOT) level than the control group.
Supplementation also improved both freshwater and oxidative stress resistances.
Interestingly, the fish fed diet groups AMP-0.2 and AMP-0.4 showed the least
oxidative stress condition. Finally it is concluded that, dietary AMP
supplementation enhanced the growth, digestibility, immune response and stress
resistance of red sea bream. The regression analysis revealed that a dietary AMP
supplementation between 0.2 and 0.4% supported weight gain and lysozyme activity
as a marker of immune functions for red sea bream, which is also inline with the
most of the growth and health performance parameters of fish under present
experimental conditions.
PMID- 27514787
TI - Cloning, characterization, and expression of the macrophage migration inhibitory
factor gene from the black tiger shrimp (Penaeus monodon).
AB - Macrophage migration inhibitory factor (MIF) is an ancient cytokine that engages
in innate immune system of vertebrates and invertebrates. In this study, the MIF
gene homologue (PmMIF) was cloned from the black tiger shrimp, Penaeus monodon.
The full-length cDNA sequence of PmMIF was 838 bp and contained 78 bp 5'
untranslated region (UTR) and 397 bp 3' UTR, and an open reading frame (ORF) of
363 bp which coded 120 amino acids (aa). Multiple alignment analysis showed that
the deduced amino acid sequence shared 98% identities with MIF from closely
related species of Litopenaeus vannamei. Quantitative real-time PCR (qRT-PCR)
analysis indicated that PmMIF was highly expression observed in hepatotpancreas
and gills. After Vibrio harveyi challenge, PmMIF mRNA level in hepatopancreas and
gills were sharply up-regulated at 6 h post-injection, and reached the maximum at
12 h. PmMIF expression level in the hepatopancreas and gills were up-regulated
markedly under low (2.3%) and high (4.3%) salinity exposure, respectively. PmMIF
expression level in gills increased significantly at 12 h and reached peak values
(2.5- fold, 6.4-fold and 1.8-fold compared with the control) at 12 h, 48 h and 12
h after zinc, cadmium and copper exposure, respectively. In the hepatopancreas,
the expression of PmMIF reached maximum levels (8.5- fold, 6.2-fold and 2.1-fold
compared with the control) at 24 h, 6 h and 48 h after zinc, cadmium and copper
exposure, respectively. All the results indicate that PmMIF plays an important
role in responding in the innate immune system of shrimps.
PMID- 27514788
TI - Grouper (Epinephelus coioides) BCR signaling pathway was involved in response
against Cryptocaryon irritans infection.
AB - B cell antigen receptor (BCR) plays a crucial role in B cell development and
antibody production. It comprises membrane immunoglobulin non-covalently
associated with CD79a/CD79b heterodimer. After B cell activation, initial
extracellular signals are transduced by BCR complex and amplified by two protein
tyrosine kinases, LYN and SYK, which then trigger various pathways. In the
present study, we cloned grouper genes for BCR accessory molecules, EcCD79a (669
bp) and EcCD79b (639 bp), as well as two protein tyrosine kinases, EcLYN (1482
bp) and EcSYK (1854 bp). Homology analysis showed that all four molecules had a
relatively high amino acid identity compared with those in other animals. Among
them, they all shared the highest identity with Takifugu rubripes (EcCD79a 49%,
EcCD79b 52%, EcLYN 82% and EcSYK 77%). The conserved features and important
functional residues were analyzed. Together with IgM and IgT, tissue distribution
analysis showed that all six molecules were mainly expressed in immune organs,
particularly systematic immune organs. In groupers infected with Cryptocaryon
irritans, up-regulation of EcCD79a and b, EcIgM and EcIgT were not seen in the
early stage skin and gill until 14-21 days. Up-regulation of EcCD79a was seen in
head kidney at most time points, while EcCD79a and b were only significantly up
regulated in day 14 spleen. Significant up-regulation of EcIgT were seen in day
21 head kidney and day 1, day14 spleen. Significant up-regulation of EcIgM were
seen in day 1 head kidney and 12 h spleen. In addition, two protein kinase genes,
EcLYN and EcSYK, were up-regulated in the skin at most time points, which
suggested that B cells may be activated at the skin local infection site.
PMID- 27514789
TI - Transapical tricuspid valve-in-ring implantation: An alternative approach to a
challenging clinical scenario.
AB - We report on a transapical tricuspid valve-in-ring implantation performed via
right ventricular apex using the Sapien-XT-prosthesis. A 57-year-old woman with
recurrent episodes of right heart failure and three previous sternotomies,
including tricuspid valve repair with a 32 mm Carpentier-Edwards-Classic
annuloplasty ring was admitted due to recurrent severe tricuspid regurgitation.
Given the excessive surgical risk, a 29 mm Sapien-XT-prosthesis was selected for
valve-in-ring implantation. Transapical valve-in-ring implantation procedure was
uneventful. Predischarge echocardiography showed only trace paravalvular
tricuspid regurgitation in the septal region. Transapical approach via right
ventricular apex is a viable alternative for tricuspid valve-in-ring implantation
in selected high-risk patients. (c) 2016 Wiley Periodicals, Inc.
PMID- 27514790
TI - Is Ammonium Peroxydisulate Indispensable for Preparation of Aniline-Derived Iron
Nitrogen-Carbon Electrocatalysts?
AB - Iron and nitrogen co-doped carbon (Fe-N-C) materials are among the most active
non-precious metal catalysts that could replace Pt-based electrocatalysts for the
oxygen reduction reaction (ORR) in fuel cells and metal-air batteries. The
synthesis of the Fe-N-C catalysts often involves the use of aniline as the
precursor for both N and C and ammonium peroxydisulfate (APS) as an indispensable
oxidative initiator for aniline polymerization. Herein, a detailed structure and
catalytic ORR performance comparison of aniline-derived Fe-N-C catalysts
synthesized with and without the use of APS is reported. The APS-free
preparation, which uses Fe(III) ions as the Fe source as well as the aniline
polymerization initiator, results in a simple Fe-N-C catalyst with a high
activity for the ORR. We show that APS is not necessary for the preparation and
even detrimental to the performance of the catalyst.
PMID- 27514791
TI - Initial Molecular Recognition Steps of McjA Precursor during Microcin J25 Lasso
Peptide Maturation.
AB - Microcin J25 (MccJ25) has emerged as an excellent model to understand the
maturation of ribosomal precursor peptides into the entangled lasso fold. MccJ25
biosynthesis relies on the post-translational modification of the precursor McjA
by the ATP-dependent protease McjB and the lactam synthetase McjC. Here, using
NMR spectroscopy, we showed that McjA is an intrinsically disordered protein
without detectable conformational preference, which emphasizes the active role of
the maturation machinery on the three-dimensional folding of MccJ25. We further
showed that the N-terminal region of the leader peptide is involved in
interaction with both maturation enzymes and identified a predominant interaction
of V43-S55 in the core McjA sequence with McjC. Moreover, we demonstrated that
residues K23-Q34 in the N-terminal McjA leader peptide tend to adopt a helical
conformation in the presence of membrane mimics, implying a role in directing
McjA to the membrane in the vicinity of the lasso synthetase/export machinery.
These data provide valuable insights into the initial molecular recognition steps
in the MccJ25 maturation process.
PMID- 27514792
TI - Hypoparathyroidism: A rare mimic of amyotrophic lateral sclerosis.
AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) carries a grim prognosis.
Various ALS mimics have been reported and should be excluded before confirming
this diagnosis. METHODS: We report the case of a 61-year-old man who presented
with progressively worsening limb weakness and dysphagia. His examination showed
mixed upper and lower motor neuron signs without sensory impairment. ALS was
suspected, however, atypical diffuse pain prompted diagnostic work-up to exclude
other causes. RESULTS: Electrodiagnostic testing was suggestive of a sensorimotor
polyneuropathy with superimposed diffuse active denervation suspicious for
anterior horn cell degeneration. Brain MRI showed bilateral basal ganglia and
thalamic calcifications. Laboratory studies confirmed the diagnosis of
hypoparathyroidism. Treatment with calcium and vitamin D resulted in significant
improvement at 6 months follow-up. CONCLUSIONS: Hypoparathyroidism, a treatable
endocrinopathy, can rarely present clinically as ALS. In atypical cases, this
should be ruled out before making a final diagnosis. Muscle Nerve, 2016 Muscle
Nerve 55: 437-439, 2017.
PMID- 27514793
TI - Preparation of Magnesium, Cobalt and Nickel Ferrite Nanoparticles from Metal
Oxides using Deep Eutectic Solvents.
AB - Natural deep eutectic solvents (DESs) dissolve simple metal oxides and are used
as a reaction medium to synthesize spinel-type ferrite nanoparticles MFe2 O4
(M=Mg, Zn, Co, Ni). The best results for phase-pure spinel ferrites are obtained
with the DES consisting of choline chloride (ChCl) and maleic acid. By employing
DESs, the reactions proceed at much lower temperatures than usual for the
respective solid-phase reactions of the metal oxides and at the same temperatures
as synthesis with comparable calcination processes using metal salts. The method
therefore reduces the overall required energy for the nanoparticle synthesis.
Thermogravimetric analysis shows that the thermolysis process of the eutectic
melts in air occurs in one major step. The phase-pure spinel-type ferrite
particles are thoroughly characterized by X-ray diffraction, diffuse-reflectance
UV/Vis spectroscopy, and scanning electron microscopy. The properties of the
obtained nanoparticles are shown to be comparable to those obtained by other
methods, illustrating the potential of natural DESs for processing metal oxides.
PMID- 27514796
TI - The anterolateral thigh flap for soft tissue reconstruction in patients with
tongue squamous cell carcinoma.
AB - BACKGROUND: Surgery remains the first choice of treatment for tongue cancer.
Immediate reconstruction should be performed after wide resection of tumour. The
aim of this study was to evaluate the anterolateral thigh flap for reconstruction
of lingual defects. METHODS: We report 39 consecutive oral tongue squamous cell
carcinoma patients who underwent lingual reconstruction with the anterolateral
thigh flap between 2009 and 2010. RESULTS: The width of the skin island was 4 to
5 cm and the length of the skin island was 6 to 8 cm in 31 patients with T2
tumour, while the width of the skin island was 5.5 to 6 cm and the length of the
skin island was 9 to 12 cm in 8 patients with T3/4 tumours. The all flap survival
rate was 97.5 % in our series. CONCLUSIONS: We could obtain sufficient flap
volume using the anterolateral thigh flap for tongue reconstruction. The single
perforator-based anterolateral thigh flap is a good option for soft tissue
reconstruction in patients with oral tongue squamous cell carcinoma.
PMID- 27514798
TI - Global RT-PCR and RT-qPCR Analysis of the mRNA Expression of the Human PTPome.
AB - Comprehensive comparative gene expression analysis of the tyrosine phosphatase
superfamily members (PTPome) under cell- or tissue-specific growth conditions may
help to define their individual and specific role in physiology and disease. Semi
quantitative and quantitative PCR are commonly used methods to analyze and
measure gene expression. Here, we describe technical aspects of PTPome mRNA
expression analysis by semi-quantitative RT-PCR and quantitative RT-PCR (RT
qPCR). We provide a protocol for each method consisting in reverse transcription
followed by PCR using a global platform of specific PTP primers. The chapter
includes aspects from primer validation to the setup of the PTPome RT-qPCR
platform. Examples are given of PTP-profiling gene expression analysis using a
human breast cancer cell line upon long-term or short-term treatment with cell
signaling-activation agents.
PMID- 27514797
TI - The Extended Family of Protein Tyrosine Phosphatases.
AB - In higher eukaryotes, the Tyr phosphorylation status of cellular proteins results
from the coordinated action of Protein Tyrosine Kinases (PTKs) and Protein
Tyrosine Phosphatases (PTPs). PTPs have emerged as highly regulated enzymes with
diverse substrate specificity, and proteins with Tyr-dephosphorylation or Tyr
dephosphorylation-like properties can be clustered as the PTPome. This includes
proteins from the PTP superfamily, which display a Cys-based catalytic mechanism,
as well as enzymes from other gene families (Asp-based phosphatases, His-based
phosphatases) that have converged in protein Tyr-dephosphorylation-related
functions by using non-Cys-based catalytic mechanisms. Within the Cys-based
members of the PTPome, classical PTPs dephosphorylate specific phosphoTyr (pTyr)
residues from protein substrates, whereas VH1-like dual-specificity PTPs
dephosphorylate pTyr, pSer, and pThr residues, as well as nonproteinaceous
substrates, including phosphoinositides and phosphorylated carbohydrates. In
addition, several PTPs have impaired catalytic activity as a result of amino acid
substitutions at their active sites, but retain regulatory functions related with
pTyr signaling. As a result of their relevant biological activity, many PTPs are
linked to human disease, including cancer, neurodevelopmental, and metabolic
diseases, making these proteins important drug targets and molecular markers in
the clinic. Here, a brief overview on the biochemistry and physiology of the
different groups of proteins that belong to the mammalian PTPome is presented.
PMID- 27514799
TI - Expression, Purification, and Kinetic Analysis of PTP Domains.
AB - Protein tyrosine phosphatases (PTP) are a large group of enzymes which work
together with protein tyrosine kinases to control the tyrosine phosphorylation of
proteins, thus playing a major role in cellular signaling. Here, we provide
detailed protocols for expression and purification of the catalytic domain of
RPTPMU and full length Eya3 as well as the extracellular region of PTPBR7.
Methods are described for evaluation of the purity of the recombinant proteins
thus obtained. For the purified Eya3 phosphatase we provide protocols for enzyme
activity assay using either chromogenic, fluorescent, or peptide substrates.
Determination of kinetic parameters by different graphical and computer-based
procedures is also described.
PMID- 27514800
TI - Peptide Microarrays for Real-Time Kinetic Profiling of Tyrosine Phosphatase
Activity of Recombinant Phosphatases and Phosphatases in Lysates of Cells or
Tissue Samples.
AB - A high-throughput method for the determination of the kinetics of protein
tyrosine phosphatase (PTP) activity in a microarray format is presented, allowing
real-time monitoring of the dephosphorylation of a 3-nitro-phosphotyrosine
residue. The 3-nitro-phosphotyrosine residue is incorporated in potential PTP
substrates. The peptide substrates are immobilized onto a porous surface in
discrete spots. After dephosphorylation by a PTP, a 3-nitrotyrosine residue is
formed that can be detected by a specific, sequence-independent antibody. The
rate of dephosphorylation can be measured simultaneously on 12 microarrays, each
comprising three concentrations of 48 clinically relevant peptides, using 1.0-5.0
MUg of protein from a cell or tissue lysate or 0.1-2.0 MUg of purified
phosphatase. The data obtained compare well with solution phase assays involving
the corresponding unmodified phosphotyrosine substrates. This technology,
characterized by high-throughput (12 assays in less than 2 h), multiplexing and
low sample requirements, facilitates convenient and unbiased investigation of the
enzymatic activity of the PTP enzyme family, for instance by profiling of PTP
substrate specificities, evaluation of PTP inhibitors and pinpointing changes in
PTP activity in biological samples related to diseases.
PMID- 27514801
TI - Tailor-Made Protein Tyrosine Phosphatases: In Vitro Site-Directed Mutagenesis of
PTEN and PTPRZ-B.
AB - In vitro site-directed mutagenesis (SDM) of protein tyrosine phosphatases (PTPs)
is a commonly used approach to experimentally analyze PTP functions at the
molecular and cellular level and to establish functional correlations with PTP
alterations found in human disease. Here, using the tumor-suppressor PTEN and the
receptor-type PTPRZ-B (short isoform from PTPRZ1 gene) phosphatases as examples,
we provide a brief insight into the utility of specific mutations in the
experimental analysis of PTP functions. We describe a standardized, rapid, and
simple method of mutagenesis to perform single and multiple amino acid
substitutions, as well as deletions of short nucleotide sequences, based on one
step inverse PCR and DpnI restriction enzyme treatment. This method of SDM is
generally applicable to any other protein of interest.
PMID- 27514802
TI - Assays to Measure PTEN Lipid Phosphatase Activity In Vitro from Purified Enzyme
or Immunoprecipitates.
AB - PTEN is a one of the most frequently mutated tumor suppressors in human cancers.
It is essential for regulating diverse biological processes and through its lipid
phosphatase activity regulates the PI 3-Kinase signaling pathway. Sensitive
phosphatase assays are employed to study the catalytic activity of PTEN against
phospholipid substrates. Here we describe protocols to assay PTEN lipid
phosphatase activity using either purified enzyme (purified PTEN lipid
phosphatase assay) or PTEN immunopurified from tissues or cultured cells
(cellular IP PTEN lipid phosphatase assay) against vesicles containing
radiolabeled PIP3 substrate.
PMID- 27514803
TI - Assessing the Biological Activity of the Glucan Phosphatase Laforin.
AB - Glucan phosphatases are a recently discovered family of enzymes that
dephosphorylate either starch or glycogen and are essential for proper starch
metabolism in plants and glycogen metabolism in humans. Mutations in the gene
encoding the only human glucan phosphatase, laforin, result in the fatal,
neurodegenerative, epilepsy known as Lafora disease. Here, we describe
phosphatase assays to assess both generic laforin phosphatase activity and
laforin's unique glycogen phosphatase activity.
PMID- 27514804
TI - Discovery and Evaluation of PRL Trimer Disruptors for Novel Anticancer Agents.
AB - Overexpression of PRL phosphatases (PRL1, PRL2, and PRL3) has been found in a
variety of late-stage tumors and their distant metastatic sites. Therefore, the
oncogenic PRL phosphatases represent intriguing targets for cancer therapy. There
is considerable interest in identifying small molecule inhibitors targeting PRLs
as novel anticancer agents. However, it has been difficult to acquire phosphatase
activity-based PRL inhibitors due to the unusual wide and shallow catalytic
pockets of PRLs revealed by crystal structure studies. Here, we present a novel
method to identify PRL1 inhibitors by targeting the PRL1 trimer interface and the
procedure to characterize their biochemical and cellular activity.
PMID- 27514805
TI - Analyzing Pseudophosphatase Function.
AB - Pseudophosphatases regulate signal transduction cascades, but their mechanisms of
action remain enigmatic. Reflecting this mystery, the prototypical
pseudophosphatase STYX (phospho-serine-threonine/tyrosine-binding protein) was
named with allusion to the river of the dead in Greek mythology to emphasize that
these molecules are "dead" phosphatases. Although proteins with STYX domains do
not catalyze dephosphorylation, this in no way precludes their having other
functions as integral elements of signaling networks. Thus, understanding their
roles in signaling pathways may mark them as potential novel drug targets. This
chapter outlines common strategies used to characterize the functions of
pseudophosphatases, using as an example MK-STYX [mitogen-activated protein kinase
(MAPK) phospho-serine-threonine/tyrosine binding], which has been linked to
tumorigenesis, apoptosis, and neuronal differentiation. We start with the
importance of "restoring" (when possible) phosphatase activity in a
pseudophosphatase so that the active mutant may be used as a comparison control
throughout immunoprecipitation and mass spectrometry analyses. To this end, we
provide protocols for site-directed mutagenesis, mammalian cell transfection, co
immunoprecipitation, phosphatase activity assays, and immunoblotting that we have
used to investigate MK-STYX and the active mutant MK-STYXactive. We also
highlight the importance of utilizing RNA interference (RNAi) "knockdown"
technology to determine a cellular phenotype in various cell lines. Therefore, we
outline our protocols for introducing short hairpin RNA (shRNA) expression
plasmids into mammalians cells and quantifying knockdown of gene expression with
real-time quantitative PCR (qPCR). A combination of cellular, molecular,
biochemical, and proteomic techniques has served as powerful tools in identifying
novel functions of the pseudophosphatase MK-STYX. Likewise, the information
provided here should be a helpful guide to elucidating the function of other
pseudophosphatases.
PMID- 27514806
TI - Crystallization of PTP Domains.
AB - Protein crystallography is the most powerful method to obtain atomic resolution
information on the three-dimensional structure of proteins. An essential step
towards determining the crystallographic structure of a protein is to produce
good quality crystals from a concentrated sample of purified protein. These
crystals are then used to obtain X-ray diffraction data necessary to determine
the 3D structure by direct phasing or molecular replacement if the model of a
homologous protein is available. Here, we describe the main approaches and
techniques to obtain suitable crystals for X-ray diffraction. We include tools
and guidance on how to evaluate and design the protein construct, how to prepare
Se-methionine derivatized protein, how to assess the stability and quality of the
sample, and how to crystallize and prepare crystals for diffraction experiments.
While general strategies for protein crystallization are summarized, specific
examples of the application of these strategies to the crystallization of PTP
domains are discussed.
PMID- 27514807
TI - NMR Spectroscopy to Study MAP Kinase Binding to MAP Kinase Phosphatases.
AB - NMR spectroscopy and other solution methods are increasingly being used to obtain
novel insights into the mechanisms by which MAPK regulatory proteins bind and
direct the activity of MAPKs. Here, we describe how interactions between the MAPK
p38alpha and its regulatory proteins are studied using NMR spectroscopy,
isothermal titration calorimetry, and small angle X-ray scattering (SAXS).
PMID- 27514808
TI - Visualizing and Quantitating the Spatiotemporal Regulation of Ras/ERK Signaling
by Dual-Specificity Mitogen-Activated Protein Phosphatases (MKPs).
AB - The spatiotemporal regulation of the Ras/ERK pathway is critical in determining
the physiological and pathophysiological outcome of signaling. Dual-specificity
mitogen-activated protein kinase (MAPK) phosphatases (DUSPs or MKPs) are key
regulators of pathway activity and may also localize ERK to distinct subcellular
locations. Here we present methods largely based on the use of high content
microscopy to both visualize and quantitate the subcellular distribution of
activated (p-ERK) and total ERK in populations of mouse embryonic fibroblasts
derived from mice lacking DUSP5, a nuclear ERK-specific MKP. Such methods in
combination with rescue experiments using adenoviral vectors encoding wild-type
and mutant forms of DUSP5 have allowed us to visualize specific defects in ERK
regulation in these cells thus confirming the role of this phosphatase as both a
nuclear regulator of ERK activity and localization.
PMID- 27514809
TI - In Situ Proximity Ligation Assay (In Situ PLA) to Assess PTP-Protein
Interactions.
AB - Spatiotemporal aspects of protein-tyrosine phosphatase (PTP) activity and
interaction partners for many PTPs are elusive. We describe here an elegant and
relatively simple method, in situ proximity ligation assay (in situ PLA), which
can be used to address these issues. The possibility to detect endogenous
unmodified proteins in situ and to visualize individual interactions with spatial
resolution is the major advantage of this technique. We provide protocols
suitable to monitor association of the transmembrane PTPs PTPRJ/DEP-1/CD148 and
PTPRB/VE-PTP with their substrates, the receptor tyrosine kinases FMS-like
tyrosine kinase 3 (FLT3/CD135), and Tie2 and vascular endothelial growth factor
receptor 2 (VEGFR2), respectively. Detailed description of method development and
reagents as well as highlighting of critical factors will enable the reader to
apply the method successfully to other PTP-protein interactions.
PMID- 27514810
TI - Use of Dominant-Negative/Substrate Trapping PTP Mutations to Search for PTP
Interactors/Substrates.
AB - Phosphorylation of proteins on tyrosine residues is the consequence of
coordinated action of tyrosine kinases (TKs), and protein tyrosine phosphatases
(PTPs). Together, they regulate intermolecular interactions, subcellular
localization, and activity of a variety of proteins. The level of total protein
associated tyrosine phosphorylation in eukaryotic cells is only a small fraction
of the total phosphorylation. PTPs, which have high specific activity compared to
tyrosine kinases, play an important role in maintaining the tyrosine
phosphorylation state of proteins and regulate signal transduction pathways and
cellular responses. PTPs depend on specific invariant residues that enable
binding to substrates phosphorylated at tyrosine and aid catalytic activity.
Identification of PTP substrates has helped understand their role in distinct
intracellular signaling pathways. Because of their high specific activity, the
interaction between tyrosine phosphatases and their substrates is often very
transient in the cellular context, and therefore identification of physiological
substrates has been difficult. Single-site mutations in the enzymes stabilize
interaction between the enzyme and its targets and have been used extensively to
identify substrates. The mutations are either of the catalytic cysteine (Cys)
residue or other invariant residues and have been classified as substrate
trapping mutants (STMs). These mutants often serve as dominant negatives that can
inactivate effector functions of a specific PTP within cells. Considering their
association with human disorders, inhibiting specific PTPs is important
therapeutically. Since the catalytic domains are largely conserved, developing
small-molecule inhibitors to a particular enzyme has proven difficult and
therefore alternate strategies to block functions of individual enzymes are
seriously being investigated. We provide a description of methods that will be
useful to design strategies of using dominant-negative and substrate-trapping
mutants for identifying novel interacting partners and substrates of PTPs.
PMID- 27514811
TI - Detection and Identification of Ligands for Mammalian RPTP Extracellular Domains.
AB - Receptor protein tyrosine phosphatases (RPTPs) form a group of over 20 enzymes in
vertebrates, each with unique ectodomains subject to potential extracellular
interactions with ligands. It has recently become clear that a remarkably diverse
range of ligands exist, including homophilic binders, adhesion molecules,
neurotrophin receptors, and proteoglycans. Individual RPTPs can bind several
ligands, and vice versa, suggesting that complex cell signaling networks exist.
The identification of RPTP ligands and where they are located in tissues remains
a challenge for a large number of these enzymes. Here we describe some powerful
methods that have proved successful for several research groups, leading to our
improved understanding of RPTP-ligand interactions and functional regulation.
PMID- 27514812
TI - Production of Osteoclasts for Studying Protein Tyrosine Phosphatase Signaling.
AB - Osteoclasts, specialized cells that degrade bone, are key components of the
cellular system that regulates and maintains bone homeostasis. Aberrant function
of osteoclasts can lead to pathological loss or gain of bone mass, such as in
osteopetrosis, osteoporosis, and several types of cancer that metastasize to
bone. Phosphorylation of osteoclast proteins on tyrosine residues is critical for
formation of osteoclasts and for their proper function and responses to
physiological signals. Here we describe preparation and growth of osteoclasts
from bone marrow of mice, use of viral vectors to downregulate expression of
endogenous proteins and to express exogenous proteins in osteoclasts, and
analysis of signaling processes triggered by M-CSF, estrogen, and physical
contact with matrix in these cells.
PMID- 27514813
TI - Functional Analysis of Protein Tyrosine Phosphatases in Thrombosis and
Hemostasis.
AB - Platelets are small blood cells derived from cytoplasmic fragments of
megakaryocytes and play an essential role in thrombosis and hemostasis. Platelet
activation depends on the rapid phosphorylation and dephosphorylation of key
signaling molecules, and a number of kinases and phosphatases have been
identified as major regulators of platelet function. However, the investigation
of novel signaling proteins has suffered from technical limitations due to the
anucleate nature of platelets and their very limited levels of mRNA and de novo
protein synthesis. In the past, experimental methods were restricted to the
generation of genetically modified mice and the development of specific
antibodies. More recently, novel (phospho)proteomic technologies and
pharmacological approaches using specific small-molecule inhibitors have added
additional capabilities to investigate specific platelet proteins.In this
chapter, we report methods for using genetic and pharmacological approaches to
investigate the function of platelet signaling proteins. While the described
experiments focus on the role of the dual-specificity phosphatase 3 (DUSP3) in
platelet signaling, the presented methods are applicable to any signaling enzyme.
Specifically, we describe a testing strategy that includes (1) aggregation and
secretion experiments with mouse and human platelets, (2) immunoprecipitation and
immunoblot assays to study platelet signaling events, (3) detailed protocols to
use selected animal models in order to investigate thrombosis and hemostasis in
vivo, and (4) strategies for utilizing pharmacological inhibitors on human
platelets.
PMID- 27514814
TI - Functional Analysis of Dual-Specificity Protein Phosphatases in Angiogenesis.
AB - Therapeutic perspectives targeting angiogenesis in cancer stimulated an intense
investigation of the mechanisms triggering and governing angiogenic processes.
Several publications have highlighted the importance of typical dual-specificity
phosphatases (DSPs) or MKPs in endothelial cells and their role in controlling
different biological functions implicated in angiogenesis such as migration,
proliferation, apoptosis, tubulogenesis, and cell adhesion. However, among
atypical DSPs, the only one investigated in angiogenesis was DUSP3. We recently
identified this DSP as a new key player in endothelial cells and angiogenesis. In
this chapter we provide with detailed protocols and models used to investigate
the role of DUSP3 in endothelial cells and angiogenesis. We start the chapter
with an overview of the role of several DSPs in angiogenesis. We continue with
providing a full description of a highly efficient transfection protocol to
deplete DUSP3 using small interfering RNA (siRNA) in the primary human umbilical
vein endothelial cells (HUVEC). We next describe the major assays used to
investigate different processes involved in angiogenesis such as tube formation
assay, proliferation assay and spheroids sprouting assay. We finish the chapter
by validating our results in DUSP3-knockout mice using in vivo angiogenesis
assays such as Matrigel plug and Lewis lung carcinoma cell subcutaneous xenograft
model followed by anti-CD31 immunofluorescence and ex vivo aortic ring assay. All
methods described can be adapted to other phosphatases and signaling molecules.
PMID- 27514815
TI - Studying Protein-Tyrosine Phosphatases in Zebrafish.
AB - Protein-tyrosine phosphatases (PTPs) are a large family of signal transduction
regulators that have an essential role in normal development and physiology.
Aberrant activation or inactivation of PTPs is at the basis of many human
diseases. The zebrafish, Danio rerio, is being used extensively to model major
aspects of development and disease as well as the mechanism of regeneration of
limbs and vital organs, and most classical PTPs have been identified in
zebrafish. Zebrafish is an excellent model system for biomedical research because
the genome is sequenced, zebrafish produce a large number of offspring, the eggs
develop outside the mother and are transparent, facilitating intravital imaging,
and transgenesis and (site-directed) mutagenesis are feasible. Together, these
traits make zebrafish amenable for the analysis of gene and protein function. In
this chapter we cover three manipulations of zebrafish embryos that we have used
to study the effects of PTPs in development, regeneration, and biochemistry.
Microinjection at the one-cell stage is at the basis of many zebrafish
experiments and is described first. This is followed by a description for
measuring regeneration of the embryonic caudal fin, a powerful and robust
physiological assay. Finally, the considerable but manageable troubleshooting of
several complications associated with preparing zebrafish embryos for
immunoblotting is explained. Overall, this chapter provides detailed protocols
for manipulating zebrafish embryo samples with a compilation of tips collected
through extensive experience from the zebrafish research community.
PMID- 27514816
TI - Live Staining of Drosophila Embryos with RPTP Fusion Proteins to Detect and
Characterize Expression of Cell-Surface RPTP Ligands.
AB - The activity and/or localization of receptor tyrosine kinases and phosphatases
are controlled by binding to cell-surface or secreted ligands. Identification of
ligands for receptor tyrosine phosphatases (RPTPs) is essential for understanding
their in vivo functions during development and disease. Here we describe a novel
in vivo method to identify ligands and binding partners for RPTPs by staining
live-dissected Drosophila embryos. Live dissected embryos are incubated with RPTP
fusion proteins to detect ligand binding in embryos. This method can be
streamlined to perform large-scale screens for ligands as well as to search for
embryonic phenotypes.
PMID- 27514817
TI - Methods to Study Protein Tyrosine Phosphatases Acting on Yeast MAPKs.
AB - Mitogen activated protein kinases (MAPK) pathways play a key role in
orchestrating the eukaryotic cellular response to different stimuli. In this
process, phosphorylation of both conserved threonine and tyrosine residues of
MAPKs is essential for their activation. Identification of tyrosine and dual
specificity protein phosphatases capable of dephosphorylating these phosphosites
is thus critical to gain insight into their regulation. Due to the conservation
of pivotal elements in eukaryotic signaling, yeast has turned into a valuable
tool to increase the knowledge of MAPK signaling in other cell types. Here we
describe an in vivo method to evaluate the capacity of a protein, from yeast or
other origin, to act as a MAPK phosphatase. It relies on the ability of the
phosphatase to reduce, when overexpressed, both the amount of activated MAPK and
the transcription from a specific promoter regulated by the corresponding
pathway. To this end, the pathway has to be previously activated, preferentially
through overexpression of a hyperactive allele of an upstream component within
the MAPK module. Additionally, the ability of an overexpressed "trapping"
inactive phosphatase version to modify these readouts is also analyzed. Western
blotting analysis with specific anti-phospho MAPK antibodies and flow cytometry
based determination of fluorescence produced by GFP whose expression is driven by
MAPK-regulated promoters are the selected techniques for monitoring these
readouts.
PMID- 27514818
TI - Transmission of biology and culture among post-contact Native Americans on the
western Great Plains.
AB - The transmission of genes and culture between human populations has major
implications for understanding potential correlations between history,
biological, and cultural variation. Understanding such dynamics in 19th century,
post-contact Native Americans on the western Great Plains is especially
challenging given passage of time, complexity of known dynamics, and difficulties
of determining genetic patterns in historical populations for whom, even today,
genetic data for their descendants are rare. Here, biometric data collected under
the direction of Franz Boas from communities penecontemporaneous with the classic
bison-hunting societies, were used as a proxy for genetic variation and analyzed
together with cultural data. We show that both gene flow and "culture flow" among
populations on the High Plains were mediated by geography, fitting a model of
isolation-by-distance. Moreover, demographic and cultural exchange among these
communities largely overrode the visible signal of the prior millennia of
cultural and genetic histories of these populations.
PMID- 27514819
TI - Mitochondria-Mediated Protein Regulation Mechanism of Polymorphs-Dependent
Inhibition of Nanoselenium on Cancer Cells.
AB - The present study was (i) to prepare two types of selenium nanoparticles, namely
an amorphous form of selenium quantum dots (A-SeQDs) and a crystalline form of
selenium quantum dots (C-SeQDs); and (ii) to investigate the nano-bio
interactions of A-SeQDs and C-SeQDs in MCF-7, HepG2, HeLa, NIH/3T3, L929 cells
and BRL-3A cells. It was found that A-SeQDs could induce the mitochondria
mediated apoptosis, necrosis and death of cells, while C-SeQDs had much weaker
effects. This polymorphs-dependent anti-proliferative activity of nano-selenium
was scarcely reported. Further investigation demonstrated that A-SeQDs could
differentially regulate 61 proteins and several pathways related to stress
response, protein synthesis, cell migration and cell cycle, including "p38 MAPK
Signaling", "p53 Signaling", "14-3-3-mediated Signaling", "p70S6K Signaling" and
"Protein Ubiquitination Pathway". This was the first report to demonstrate the
involvement of protein synthesis and post-translational modification pathways in
the anti-proliferative activity associated with NMs. Compared with previously
fragmentary studies, this study use a nanomics approach combining bioinformatics
and proteomics to systematically investigate the nano-bio interactions of
selenium nanoparticles in cancer cells.
PMID- 27514820
TI - Production of human blood group B antigen epitope conjugated protein in
Escherichia coli and utilization of the adsorption blood group B antibody.
AB - BACKGROUND: In the process of ABO-incompatible (ABOi) organ transplantation,
removal of anti-A and/or B antibodies from blood plasma is a promising method to
overcome hyperacute rejection and allograft loss caused by the immune response
between anti-A and/or B antibodies and the A and/or B antigens in the recipient.
Although there are commercial columns to do this work, the application is still
limited because of the high production cost. RESULTS: In this study, the PglB
glycosylation pathway from Campylobacter jejuni was exploited to produce
glycoprotein conjugated with Escherichia coli O86:B7 O-antigen, which bears the
blood group B antigen epitope to absorb blood group B antibody in blood. The
titers of blood group B antibody were reduced to a safe level without changing
the clotting function of plasma after glycoprotein absorption of B antibodies in
the plasma. CONCLUSIONS: We developed a feasible strategy for the specific
adsorption/removal of blood group antibodies. This method will be useful in ABOi
organ transplantation and universal blood transfusion.
PMID- 27514821
TI - Brachybacterium aquaticum sp. nov., a novel actinobacterium isolated from
seawater.
AB - A pale-yellowish bacterium, strain KWS-1T, was isolated from seawater during a
study of the bacterial diversity of the marine environment of the Kanyakumari
coastal region of the Bay of Bengal, India, and was studied by using a polyphasic
taxonomic approach. Strain KWS-1T had morphological and chemotaxonomic properties
(cell-wall diamino acid, menaquinone and fatty acid profile) consistent with its
classification in the genus Brachybacterium. Phylogenetic analysis of the 16S
rRNA gene sequence showed that strain KWS-1T was related most closely to
Brachybacterium paraconglomeratum JCM 17781T, followed by Brachybacterium
saurashtrense DSM 23186T, Brachybacterium gingengisoli JCM 19356T,
Brachybacterium faecium JCM 11609T and Brachybacterium conglomeratum JCM 11608T
(98.45, 98.24, 98.12, 98.10 and 98.10 % similarity, respectively), whereas the
sequence similarity values with respect to the other Brachybacterium species with
validly published names were between 97.4 and 94.2 %. However, the DNA-DNA
hybridization values between strain KWS-1T and the five most closely related
species were less than the threshold value for species discrimination. The major
lipids were diphosphatidylglycerol, phosphatidylethanolamine,
phosphatidylglycerol and phosphatidylserine and the major quinone was menaquinone
MK-7. The DNA G+C content of strain KWS-1T was 71.8 mol%. The above data in
combination with the phenotypic distinctiveness of strain KWS-1T from other
reference strains clearly indicate that the strain represents a novel species,
for which the name Brachybacterium aquaticum sp. nov. is proposed. The type
strain is KWS-1T (=MTCC 11836T=DSM 28796T=JCM 30059T).
PMID- 27514822
TI - Analysis of 109 Consecutive Explanted Breast Implants: Correlation Between
Suspected Implant Rupture and Surgical Findings.
AB - INTRODUCTION: The use of breast implants is on the rise due to increases in
breast reconstructive and aesthetic surgery. Implant rupture is a possible
complication. Among assessment modalities for implant rupture detection, MRI is
considered the gold standard. METHODS: We conducted a prospective analysis of 57
women after breast augmentation or postmastectomy reconstruction (109 implants),
admitted to our department between 2010 and 2015 due to suspected implant
rupture. We correlated surgical findings with symptoms, physical examination,
imaging, and device specifications. RESULTS: Seventy-four explanted implants were
preoperatively suspected as ruptured. Over a third were intact and unjustifiably
explanted. MRI evaluation was the most accurate modality. Interestingly, 61 % of
ruptured implants were left-sided. Patient's age, comorbidities, smoking,
medications, presenting symptoms, implant duration, and volume did not correlate
with implant rupture. CONCLUSIONS: Our study confirmed preexisting data regarding
the importance of imaging diagnosis, with MRI being the most accurate modality in
both diagnosing and ruling out implant rupture. Interestingly, our study showed
that MRI was accurate in detecting all intact implants, unlike lower detection
rates reported in previous studies, thus preventing unnecessary explantation.
Another unique finding was that the left-sided implants were significantly prone
for rupture. As iatrogenic damage is the most common cause of implant rupture,
with most surgeons being right-handed, awareness during surgery must be
augmented, with further investigation required for potential causes of this
unexpected difference. Our study emphasizes the importance of understanding the
causes of rupture and the need for evidence-based indications regarding imaging
and replacement of implants. LEVEL OF EVIDENCE III: 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- 27514823
TI - Pharmacokinetic Effects of Cinnamic Acid, Amygdalin, Glycyrrhizic Acid and
Liquiritin on Ephedra Alkaloids in Rats.
AB - BACKGROUND AND OBJECTIVES: Ephedra alkaloids, including ephedrine (EP),
pseudoephedrine (PEP) and methylephedrine (MEP), are sympathomimetic compounds
with known toxicities but many Ephedra (Ephedrae herba) preparations, such as
Ephedra decoction, have been clinically applied for centuries. In order to
explore the possible detoxification mechanism of Ephedra alkaloids, four
representative compounds in Ephedra decoction (cinnamic acid, amygdalin,
glycyrrhizic acid and liquiritin) were studied for their pharmacokinetic effects
on Ephedra alkaloids in Sprague-Dawley rats. METHODS: Animals were randomly
divided into six groups, with six rats in each. Rats were treated orally with EP
PEP-MEP (20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP) and different combinations of
cinnamic acid (3.03 mg/kg), amygdalin (56.97 mg/kg), glycyrrhizic acid (12.42
mg/kg), liquiritin (3.79 mg/kg) with EP-PEP-MEP, and 20 mg/kg EP + 20 mg/kg PEP +
20 mg/kg MEP + 3.03 mg/kg cinnamic acid + 56.97 mg/kg amygdalin + 12.42 mg/kg
glycyrrhizic acid + 3.79 mg/kg liquiritin. Blood samples (0.5 mL) were taken from
the orbital sinus venous plexus into heparinized tubes at 5, 10, 20, 30, 45, 60,
90, 120, 180, 240, 300 and 360 min (6 rats per time point in each group)
following single administration. The concentrations of Ephedra alkaloids in rat
plasma were determined using a validated high performance liquid chromatography
method. RESULTS: Area under the concentration-time curve from 0 to 360 min (AUC0
t ) of EP, PEP and MEP were 666.99, 650.76 and 632.37 ug.min/mL, respectively.
Maximum plasma concentration (C max) of EP, PEP and MEP were 4.15, 4.08 and 3.59
MUg/mL, respectively. Mean residence time (MRT) of EP, PEP and MEP were 197.00,
173.97 and 183.87 min, respectively, when the rats were treated with EP-PEP-MEP.
Cinnamic acid increased the AUC0-t of EP while decreased C max of EP, amygdalin
and glycyrrhizic acid increased C max and AUC0-t of EP and PEP, while liquiritin
decreased AUC0-t of EP and PEP. The four representative compounds reduced MRT of
EP, PEP and MEP, four compounds decreased AUC0-t of MEP. The EP-PEP-MEP +
cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group increased AUC0-t
of EP while decreased MRT of EP, increased MRT of PEP while decreased AUC0-t of
PEP. The EP-PEP-MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin
group decreased MRT, AUC0-t and C max of MEP. CONCLUSIONS: Significant changes in
pharmacokinetic parameters of EP, PEP and MEP were observed after oral
administration with different combinations. The pharmacokinetic results reported
here might provide reference for clinical usage of Ephedra alkaloids.
PMID- 27514824
TI - Reasons for current pregnancy amongst grand multiparous Gambian women - a cross
sectional survey.
AB - BACKGROUND: While grand multiparity is now relatively rare in the developed world
it is still common in Sub Saharan Africa. Although significant resources have
been committed to providing modern contraceptive methods in the Gambia, the total
fertility rate is still high at 5.6. Determining the reasons grand multiparous
women proffer for the current pregnancy may help in understanding this trend and
tailoring appropriate messages to address any specific concerns. METHOD: A cross
sectional survey of grand multiparous women was carried out at the Royal Victoria
Teaching Hospital (now Edward Francis Small Teaching Hospital) to determine the
reasons for the current pregnancy. RESULTS: The prevalence of grand multiparity
was 26.5 % while the average parity among the study population was 7.2 (sd 1.8).
The most common reasons given for the current pregnancy were: the desire for
another child (22.8 %), the pregnancy was unplanned - a "mistake" (18.4 %) and
the need to replace a dead child (15.4 %). CONCLUSION: Grand multiparity is still
very common in The Gambia. Additional efforts are required to target those with
unplanned pregnancies. Improving child survival may also decrease the prevalence
of grand multiparity.
PMID- 27514825
TI - [Surgical treatment of de-novo scoliosis].
AB - BACKGROUND: De-novo scoliosis is most commonly associated with chronic back pain
and in 70 % of cases with neurological symptoms of the lower extremities. In
recent literature, the occurrence and severity of segmental lateral listhesis has
been discussed as being an important prognostic factor of sagittal and frontal
deformity progression. In general, operative interventions in patients with de
novo scoliosis are associated with a high rate of complications. Therefore,
conservative treatment modalities are recommended at early stages of the disease.
If conservative management fails and a sufficient reduction of the patient's
symptoms cannot be achieved, depending on the symptoms, a selective
decompression, short-segment fusion or long-instrumented reduction and fusion are
indicated. Additionally to the patient's symptoms, specific imaging diagnostics
are necessary to develop an adequate surgical treatment strategy. TREATMENT:
Selective decompression without fusion is indicated in patients with a fixed
deformity and primarily neurologic pain or deficits. In conditions of a focal
pathology as cause of significant low back pain and/or neurologic symptoms at
early stages of deformity, a short segment fusion is the treatment of choice.
However, short-segment fusion as a less-invasive procedure must not be performed
in biplanar unbalanced patients and/or advanced de-novo scoliosis. In advanced
degenerative de-novo scoliosis a long-segment reposition and fusion following an
alignment correction are needed. Standardized pre-operative planning and
perioperative management are highly critical to the post-operative success.
CONCLUSION: All operative treatment strategies in patients with de-novo scoliosis
can be successful but they require sophisticated and individual surgical
indication.
PMID- 27514826
TI - [Management of postoperative wound infections following spine surgery : First
results of a multicenter study].
AB - INTRODUCTION: The number of spinal surgeries has increased significantly in the
last decade, which has led to a correlating increase in the number of problems
related to wound healing infection. Current literature has reported a spinal
wound infection rate of 0.4 to 20 %. The gold standard for surgical restoration
of the infection is to use supportive antibiotics, but this concept of wound
management in infections is often not sufficiently standardized and shows a large
variance between individual clinics. The present study is to first collect data
on the number of wound infections, the clinic's internal standards, the use of
methods and tools and the management of revisions in Germany. MATERIAL AND
METHODS: A questionnaire has been designed for detecting the number of
postoperative wound infections, which need to be treated surgically, and the
various treatment regimens used. The questionnaire was sent to all members of the
DWG (n = 1275). An example of the questionnaire was to determine clinical
internal standards and the procedure for the initial treatment of wound
infection, the procedure for second look surgery and the number of revisions
requested to infection healing. RESULTS: The study has accepted 67 answer sheets
covering a period from June 2013-November 2013. On average, the participating
hospitals perform 582 spinal operations and an average of 8 revision surgeries
due to infection annually. The average rate of infection was 1.7 %. 55 % reported
having no fixed standard of care. 97 % reported wound irrigation and debridement
during the first revision. Indication for second look revisions was based on the
local examination of the wound conditions. On average 2.2 revisions had been
performed to reach effective wound healing. 81 % of the colleagues showed
readiness to participate in a multicenter trial. CONCLUSION: The results show
that there is a need for uniform standards in the treatment of postoperative
infections. Surgical debridement and lavage have a major role in the treatment of
infection. The overall rate of postoperative infections, of the clinics surveyed,
was approximately 1.7 % per year. The infections were healed with approximately 2
revisions utilizing variety of different treatment strategies.
PMID- 27514827
TI - [Cement augmentation of pedicle screws : Pros and cons].
AB - Cement augmentation of pedicle screws biomechanically increases screw purchase in
the bone. However, clinical complications may occur. The pros and cons of the
technique are discussed from different clinical perspectives.
PMID- 27514828
TI - [Multimodal therapy concepts for failed back surgery syndrome].
AB - Failed back surgery syndrome (FBSS) is a frequent complication (15-40 %) of
lumbar disc surgery and is rarely successfully treated by surgery with the
exception of a re-prolapse associated with radicular pain. Multimodal pain
treatment, however, is indicated by a lack of pathoanatomical correlates, unclear
cause and psychosocial risk factors.This review describes a standardized non
operative treatment starting with broad interdisciplinary clarification by
medical, psychological and physiotherapeutic means (assessment).If the conditions
for multimodal pain therapy are met, the OPS 8-918-procedure can be applied to
avoid chronic developing pain. In doing so, the already issued quality standards
and guidelines for documentation should be respected.
PMID- 27514829
TI - Combined suture and clipping for the reconstruction of a ruptured blister-like
aneurysm.
AB - Blister-like aneurysms of the internal carotid artery (ICA) present a severe
therapeutical challenge. While several reconstructive techniques are in use in
case of acute rupture sacrifice of the parent vessel may be required. We present
a combined technique of micro-sutures and clip application to repair the parent
vessel in an intraoperatively ruptured blister-like aneurysm. Following temporary
trapping of an intraoperatively ruptured 7-mm blister-like aneurysm four 8-0
nylon sutures were applied to adapt the vessel walls and support the branches of
subsequently applied mini-clips. The combination of micro-sutures and mini-clips
might be a valuable alternative to direct clipping or suturing in some cases with
intraoperative rupture of blister-like aneurysms.
PMID- 27514830
TI - Reply to: "Residency program trainee-satisfaction correlate with results of the
European board examination in neurosurgery".
PMID- 27514832
TI - Associations of acute stress and overnight heart rate with feed efficiency in
beef heifers.
AB - Proxies have the potential to accelerate feed efficiency (residual feed intake
(RFI); kg dry matter/day) improvement, assisting with the reduction of beef
cattle feed costs and environmental impact. Heart rate (HR) (beats per minute
(BPM)) is associated with feed efficiency and influenced by autonomic activity
and peripheral metabolism, suggesting HR could be used as a proxy for feed
efficiency. Objectives were to assess associations between overnight HR, lying
patterns and RFI, and between acute stress HR and RFI. Heifer calves (n=107;
408+/-28 days of age, 341+/-42.2 kg) and yearling heifers (n=36; 604+/-92 days of
age, 539+/-52.2 kg) were exposed to a performance test to determine productive
performance. Overnight HR (electrode based) and lying patterns (accelerometer
based) were monitored on a subgroup of heifer calves (n=40; 20 lowest RFI; 20
highest RFI). In the 10-min acute stress assessment, all heifers were
individually exposed to the opening and closing of an umbrella and HR before
(HRBEF), in response to (HRMAX), after (HRAFT) and change (HRCHG; HRAFT-HRBEF) as
a result of exposure were determined. Using polynomial regression, rate of HR
decrease pre-exposure (beta 1) and rates of HR increase (beta 2) and decrease
(beta 3, beta 4) post-exposure were determined. Heifer calves in the overnight
assessment were classified into equal RFI groups (low RFI; high RFI) and HR means
were treated as repeated measures and compared using multiple regression. In the
acute stress assessment, heifers were classified within cattle category into
equal RFI groups (low RFI; high RFI) and means and polynomial regression
parameters were compared using multiple regression. Low-RFI heifer calves had a
lower overnight HR (69.2 v. 72.6 BPM), similar HR change from lying to standing
intervals (8.9 v. 9.2 BPM) and similar time lying (61.1% v. 64.5%) compared with
high-RFI heifer calves. Low-RFI heifer calves had a higher absolute HRMAX (162.9
v. 145.7 BPM) and beta 2 (-0.34 v. -0.20) than high-RFI heifer calves. Low-RFI
yearling heifers had similar acute stress HR means and a lower beta 1 (0.003 v.
0.006) than high-RFI yearling heifers. Overnight HR and acute stress HR are
potential indicators of RFI in heifer calves. However, acute stress HR results
varied in yearling heifers, suggesting previous handling experience and/or age
influence stress response. Pending further development (predictive ability,
repeatability), the acute stress assessment could have potential for on-farm
application as a feed efficiency proxy in young heifers with minimal handling
experience.
PMID- 27514831
TI - Genome-wide association study of copy number variation with lung function
identifies a novel signal of association near BANP for forced vital capacity.
AB - BACKGROUND: Genome-wide association studies of Single Nucleotide Polymorphisms
(SNPs) have identified 55 SNPs associated with lung function. However, little is
known about the effect of copy number variants (CNVs) on lung function, although
CNVs represent a significant proportion of human genetic polymorphism. To assess
the effect of CNVs on lung function quantitative traits, we measured copy number
at 2788 previously characterised, common copy number variable regions in 6
independent cohorts (n = 24,237) using intensity data from SNP genotyping
experiments. We developed a pipeline for genome-wide association analysis and
meta-analysis of CNV genotypes measured across multiple studies using SNP
genotype array intensity data from different platform technologies. We then
undertook cohort-level genome-wide association studies of CNV with lung function
in a subset of 4 cohorts (n < =12,403) with lung function measurements and meta
analysed the results. Follow-up was undertaken for CNVs which were well tagged by
SNPs, in up to 146,871 individuals. RESULTS: We generated robust copy number
calls for 1962 out of 2788 (70 %) known CNV regions genome-wide, with 1103
measured with compatible class frequencies in at least 2 cohorts. We report a
novel CNV association (discovery P = 0.0007) with Forced Vital Capacity (FVC)
downstream of BANP on chromosome 16 that shows evidence of replication by a tag
SNP in two independent studies (replication P = 0.004). In addition, we provide
suggestive evidence (discovery P = 0.0002) for a role of complex copy number
variation at a previously reported lung function locus, containing the rootletin
gene CROCC, that is not tagged by SNPs. CONCLUSIONS: We demonstrate how common
CNV regions can be reliably and consistently called across cohorts, using an
existing calling algorithm and rigorous quality control steps, using SNP
genotyping array intensity data. Although many common biallelic CNV regions were
well-tagged by common SNPs, we also identified associations with untagged
mulitallelic CNV regions thereby illustrating the potential of our approach to
identify some of the missing heritability of complex traits.
PMID- 27514833
TI - Subcompartmentalization by cross-membranes during early growth of Streptomyces
hyphae.
AB - Bacteria of the genus Streptomyces are a model system for bacterial
multicellularity. Their mycelial life style involves the formation of long
multinucleated hyphae during vegetative growth, with occasional cross-walls
separating long compartments. Reproduction occurs by specialized aerial hyphae,
which differentiate into chains of uninucleoid spores. While the tubulin-like
FtsZ protein is required for the formation of all peptidoglycan-based septa in
Streptomyces, canonical divisome-dependent cell division only occurs during
sporulation. Here we report extensive subcompartmentalization in young vegetative
hyphae of Streptomyces coelicolor, whereby 1 MUm compartments are formed by
nucleic acid stain-impermeable barriers. These barriers possess the permeability
properties of membranes and at least some of them are cross-membranes without
detectable peptidoglycan. Z-ladders form during the early growth, but cross
membrane formation does not depend on FtsZ. Thus, a new level of hyphal
organization is presented involving unprecedented high-frequency
compartmentalization, which changes the old dogma that Streptomyces vegetative
hyphae have scarce compartmentalization.
PMID- 27514834
TI - Presentation of Coping Strategies Associated with Physical and Mental Health
During Health Check-ups.
AB - We identified coping behaviors during regular health check-ups and examined
whether they were related to physical and mental health. We assessed coping
strategies with the Brief COPE scale in 201 people who underwent a regular health
check-up in a clinic. We found several significant relationships between coping
and physical/psychological conditions presented in health check-up: Humor and
systolic blood pressure, Substance use and high-density lipoprotein cholesterol,
Venting and low-density lipoprotein cholesterol, Self-blame and depression, and
Behavioral disengagement and sleep disorder. By evaluating coping strategies and
screening depression as part of a regular health check-up, General practitioner
can provide psychological intervention such as cognitive behavioral therapy which
may improve both mental and physical health of the people.
PMID- 27514835
TI - Regulatory roles of interferon-inducible protein 204 on differentiation and
vasculogenic activity of endothelial progenitor cells.
AB - BACKGROUND: Endothelial progenitor cells (EPCs) have shown great potential in
angiogenesis either by their differentiation into endothelial cells or by
secretion of angiogenic factors. Interferon-inducible protein 204 (Ifi204) has
been reported to participate in the regulation of cell growth and
differentiation. However, its role in differentiation of EPCs remains unknown. We
proposed that Ifi204 could modulate the differentiation and regenerative
abilities of EPCs. METHODS: Ifi204-expressing lentivirus and Ifi204 siRNA were
introduced into EPCs to overexpress and suppress the expression of Ifi204. Using
fluorescence-activated cell sorting, immunocytochemistry, and quantitative PCR,
endothelial markers including CD31, VE-cadherin, and vWF were detected in the
modified EPCs. An in-vitro incorporation assay and a colony-forming assay were
also performed. RESULTS: Evidence showed that Ifi204 inhibition decreased the
endothelial differentiation and vasculogenic activities of EPCs in vitro. In mice
with hindlimb ischemia, downregulation of Ifi204 in EPCs, which was tracked by
our newly synthesized nanofluorogen, impaired neovascularization, with a
corresponding reduction in hindlimb blood reperfusion by postoperative day 14.
CONCLUSIONS: Ifi204 is required for EPC differentiation and neovascularization in
vitro and in vivo. The regulatory roles of Ifi204 in EPC differentiation may
benefit the clinical therapy of ischemic vascular diseases.
PMID- 27514837
TI - Retrospective Analysis of Hanging Deaths in Ontario.
AB - Hanging deaths from investigation standpoint are rarely problematic. Unusual
circumstances can on occasion raise suspicion of foul play. Associated neck
injuries are reported in the literature with variable frequency (from 0% to
76.8%). This study retrospectively analyzed 755 hanging deaths in Ontario
(Canada) to evaluate the demographic features and circumstances of hanging
fatalities, and the frequency of hanging-related neck injuries. A number of cases
showed unusual/special circumstances (e.g., complex, double suicides,
restraints). Among 632 cases with complete autopsies, hyoid and larynx fractures
were present in 46 cases (7.3%) with the most common being isolated hyoid
fractures. The incidence of cricoid fractures was 0.5% and cervical spine
injuries, 1.1%. A higher incidence of neck injuries occurred among males, long
drop hangings, and in cases with complete suspension. There was a tendency for
the number of fractures to increase with increasing age and weight of the
deceased.
PMID- 27514836
TI - Home visiting and perinatal smoking: a mixed-methods exploration of cessation and
harm reduction strategies.
AB - BACKGROUND: Home visiting programs represent an important primary prevention
strategy for adverse prenatal health behaviors; the various ways in which home
visiting programs impact prenatal smoking cessation and reduction behaviors
remain understudied. METHODS: Mixed methods approach using a retrospective cohort
of propensity score matched home visiting clients and local-area comparison women
with first births between 2008-2014 in a large Northeast state. Multivariable
logistic and linear regression estimated third trimester prenatal tobacco smoking
cessation and reduction. Additionally, qualitative interviews were conducted with
76 home visiting clients. RESULTS: A program effect was seen for smoking
cessation such that clients who smoked less than ten cigarettes per day and those
who smoked 20 or more cigarettes per day during the first trimester were more
likely to achieve third trimester cessation than comparison women (p <0.01 and p
= 0.01, respectively). Only for heavy smokers (20 or more cigarettes during the
first trimester) was there a significant reduction in number of cigarettes smoked
by the third trimester versus comparison women (p = 0.01). Clients expressed the
difficulty of cessation, but addressed several harm-reduction strategies
including reducing smoking in the house and wearing a smoking jacket. Clients
also described smoking education that empowered them to ask others to not smoke
or adopt other harm reducing behaviors when around their children. CONCLUSIONS:
While a significant impact on smoking cessation was seen, this study finds a less
clear impact on smoking reduction among women in home visiting programs. As home
visiting programs continue to expand, it will be important to best identify
effective ways to support tobacco-related harm reduction within vulnerable
families.
PMID- 27514838
TI - BRCA to the future: towards best testing practice in the era of personalised
healthcare.
PMID- 27514839
TI - New challenges for BRCA testing: a view from the diagnostic laboratory.
AB - Increased demand for BRCA testing is placing pressures on diagnostic laboratories
to raise their mutation screening capacity and handle the challenges associated
with classifying BRCA sequence variants for clinical significance, for example
interpretation of pathogenic mutations or variants of unknown significance,
accurate determination of large genomic rearrangements and detection of somatic
mutations in DNA extracted from formalin-fixed, paraffin-embedded tumour samples.
Many diagnostic laboratories are adopting next-generation sequencing (NGS)
technology to increase their screening capacity and reduce processing time and
unit costs. However, migration to NGS introduces complexities arising from choice
of components of the BRCA testing workflow, such as NGS platform, enrichment
method and bioinformatics analysis process. An efficient, cost-effective accurate
mutation detection strategy and a standardised, systematic approach to the
reporting of BRCA test results is imperative for diagnostic laboratories. This
review covers the challenges of BRCA testing from the perspective of a
diagnostics laboratory.
PMID- 27514840
TI - Finding all BRCA pathogenic mutation carriers: best practice models.
AB - Identifying germline BRCA pathogenic mutations in patients with ovarian or breast
cancer is a crucial component in the medical management of affected patients.
Furthermore, the relatives of affected patients can be offered genetic testing.
Relatives who test positive for a germline BRCA pathogenic mutation can take
appropriate action to prevent cancer or have cancer diagnosed as early as
possible for better treatment options. The recent discovery that BRCA pathogenic
mutation status can inform treatment decisions in patients with ovarian cancer
has led to an increased demand for BRCA testing, with testing taking place
earlier in the patient care pathway. New approaches to genetic counselling may be
required to meet this greater demand for BRCA testing. This review discusses the
need for best practices for genetic counselling and BRCA testing; it examines the
challenges facing current practice and looks at adapted models of genetic
counselling.
PMID- 27514841
TI - The biological effects and clinical implications of BRCA mutations: where do we
go from here?
AB - BRCA1 and BRCA2 are tumour-suppressor genes encoding proteins that are essential
for the repair of DNA double-strand breaks by homologous recombination (HR).
Cells that lack either BRCA1 or BRCA2 repair these lesions by alternative, more
error-prone mechanisms. Individuals carrying germline pathogenic mutations in
BRCA1 or BRCA2 are at highly elevated risk of developing breast and/or ovarian
cancer. Genetic testing for germline pathogenic mutations in BRCA1 and BRCA2 has
proved to be a valuable tool for determining eligibility for cancer screening and
prevention programmes. In view of increasing evidence that the HR DNA repair
pathway can also be disrupted by sequence variants in other genes, screening for
other BRCA-like defects has potential implications for patient care.
Additionally, there is a growing argument for directly testing tumours for
pathogenic mutations in BRCA1, BRCA2 and other genes involved in HR-DNA repair as
inactivation of these genes may be strictly somatic. Tumours in which HR-DNA
repair is altered are most likely to respond to emerging targeted therapies, such
as inhibitors of poly-ADP ribose polymerase. This review highlights the
biological role of pathogenic BRCA mutations and other associated defects in DNA
damage repair mechanisms in breast and ovarian cancer, with particular focus on
implications for patient management strategies.
PMID- 27514842
TI - A case of ovarian adenosquamous carcinoma arising from endometrioid
adenocarcinoma: a case report and systematic review.
AB - BACKGROUND: The aims of this report were to describe a case of ovarian
adenosquamous carcinoma and to systematically review the pertinent literature.
METHODS: We describe a case in which a 57-year-old woman had stage IC ovarian
cancer histologically diagnosed as adenosquamous carcinoma. We also
systematically reviewed the literature using the PubMed database. CASE
PRESENTATION: Preoperative computed tomography and magnetic resonance imaging
showed a tumor measuring 14 cm in diameter and containing solid areas. Tumor
marker levels were as follows: CA125, 42.6 U/mL; CA 19-9, 134.1 U/mL; CEA, 0.9
ng/mL; and SCC, 1.6 ng/mL. The patient underwent multiple surgeries including
total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lymph node
dissection, para-aortic lymph node biopsy, and total omentectomy. Based on the
cytological features of the ascitic fluid, the tumor was diagnosed as a squamous
cell carcinoma. Histological examination of an excised specimen showed the
transition of an endometrioid adenocarcinoma to a squamous cell carcinoma. There
was no evidence of any teratomas or endometriosis-related features. We considered
the tumor to be an adenosquamous carcinoma, with the squamous cell carcinoma
component arising from the endometrioid adenocarcinoma component. After surgery,
the patient underwent 6 cycles of paclitaxel and carboplatin chemotherapy. There
has been no recurrence to date, 66 months after the initial treatment. RESULTS:
Histologically, the 8 adenosquamous carcinomas reported in the literature either
arose from the mature cystic teratoma (4 cases) or endometriosis (3 cases) or
were pure adenosquamous carcinomas (1 case). Our literature search uncovered no
cases of ovarian adenosquamous carcinomas originating from endometrioid
adenocarcinomas. CONCLUSIONS: This is the first reported case of an adenosquamous
carcinoma arising from an endometrioid adenocarcinoma. Because such tumors are
rare, their standard management is unclear.
PMID- 27514844
TI - alpha-Diamine Nickel Catalysts with Nonplanar Chelate Rings for Ethylene
Polymerization.
AB - A series of novel alpha-diamine nickel complexes, (ArNH-C(Me)-(Me)C-NHAr)NiBr2 ,
1: Ar=2,6-diisopropylphenyl, 2: Ar=2,6-dimethylphenyl, 3: Ar=phenyl), have been
synthesized and characterized. X-ray crystallographic analysis showed that the
coordination geometry of the alpha-diamine nickel complexes is markedly different
from conventional alpha-diimine nickel complexes, and that the chelate ring (N-C
C-N-Ni) of the alpha-diamine nickel complex is significantly distorted. The alpha
diamine nickel catalysts also display different steric effects on ethylene
polymerization in comparison to the alpha-diimine nickel catalyst. Increasing the
steric hindrance of the alpha-diamine ligand by substitution of the o-methyl
groups with o-isopropyl groups leads to decreased polymerization activity and
molecular weight; however, catalyst thermal stability is significantly enhanced.
Living polymerizations of ethylene can be successfully achieved using 1/Et2 AlCl
at 35 degrees C or 2/Et2 AlCl at 0 degrees C. The bulky alpha-diamine nickel
catalyst 1 with isopropyl substituents can additionally be used to control the
branching topology of the obtained polyethylene at the same level of branching
density by tuning the reaction temperature and ethylene pressure.
PMID- 27514843
TI - Reduction of Streptococcus pneumoniae in upper respiratory tract cultures and a
decreased incidence of related acute otitis media following introduction of
childhood pneumococcal conjugate vaccines in a Swedish county.
AB - BACKGROUND: The effect of pneumococcal conjugate vaccines (PCV) on invasive
pneumococcal disease is frequently reported, but the impact on upper respiratory
tract infections in a clinical setting is less documented. Our aim in this 5-year
observational study was to investigate serotype changes in a large number of
Streptococcus pneumoniae upper respiratory tract isolates following sequential
introduction of PCV7 and pneumococcal Haemophilus influenza protein D conjugate
vaccine (PHiD-CV10) in a Swedish county. METHODS: All bacterial isolates from the
upper respiratory tract (nasopharynx, sinus or middle ear fluid) from patients
with respiratory tract infections referred to a clinical microbiology laboratory
prior to (2 years 2007-2008; n = 1566) and after introduction of PCV (3 years
2011-2013; n = 1707) were prospectively collected. Microbiological findings were
compared between the two periods, and information from clinical referrals was
recorded in order to explore changes in incidence of pneumococcal acute otitis
media (AOM). RESULTS: Pneumococcal serotypes covered by PHiD-CV10 decreased from
45 to 12 % prior to and after immunization (p < 0.001), respectively. Despite non
PHiD-CV10 serotypes increased from 49 to 80 %, a significant decline of 35 % in
the absolute incidence of pneumocococal isolates (p < 0.001) was observed.
Finally, the frequency of complicated AOM caused by S. pneumoniae decreased by 32
% (p < 0.001). CONCLUSIONS: After introduction of PCV in 2009, we have observed a
significantly decreased number of pneumococcal isolates in the upper respiratory
tract, a shift to non-PHiD-CV10 serotypes, and a reduction of complicated AOM.
Our findings may have implications for future vaccine design.
PMID- 27514845
TI - Value of adding GNAS testing to pancreatic cyst fluid KRAS and carcinoembryonic
antigen analysis for the diagnosis of intraductal papillary mucinous neoplasms.
AB - BACKGROUND AND AIM: Molecular analysis of pancreatic cyst fluid (PCF) has been
proposed as a novel method for differentiating pancreatic cystic lesions (PCL).
The present study aimed to investigate the value of GNAS testing when added to
KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of
intraductal papillary mucinous neoplasms (IPMN). METHODS: Prospectively collected
endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed
retrospectively for GNAS and KRAS mutations and CEA results. IPMN were
histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA,
cytology). Performance characteristics of GNAS added to KRAS and CEA for the
diagnosis of IPMN were calculated. RESULTS: The study population consisted of 197
patients with cyst fluid test results. Cysts were histologically classified in 33
patients and by clinical criteria in 164 patients. The IPMN group included 108
patients and the non-IPMN group included 89 patients. GNAS was positive in 51
patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS
mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to
79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4%
to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS
testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple
combination was significantly better than all single tests (P < 0.05).
CONCLUSION: GNAS mutation is a highly specific test for IPMN. When GNAS testing
is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is
achieved.
PMID- 27514846
TI - Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression
in Chronic Lymphocytic Leukemia.
AB - Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
characterized by the accumulation/expansion of a clonal population of neoplastic
cells with the morphological appearance of small mature B lymphocytes in blood,
bone marrow, and lymphoid organs. CD49d, the alpha chain of the alpha4beta1
integrin heterodimer, is one of the main interactors between CLL cells and
accessory cells in the microenvironmental sites and one of the main predictors of
overall survival. In particular, CD49d is known to play a pivotal role in
mediating both cell-cell and cell-matrix interactions in CLL-involved tissues
eventually delivering prosurvival signals and protecting CLL cells from drug
induced damages. Treatment strategies targeting the alpha4beta1 integrin could
represent an interesting option in CLL. In this context, the recombinant anti
CD49d antibody natalizumab demonstrated the potential to overcome stromal cell
induced resistance of B cell lymphoma cells against cytotoxic drugs and rituximab
in vitro. Moreover, a specific interest for the CD49d molecule raises from the
clinical activity of the recently proposed inhibitors of kinases downstream the
BCR that has been recently related with the inside-out activation of the
alpha4beta1 integrin. In the review, we addressed in detail the role of CD49d in
CLL cells, including clinical impact, relationship with specific cytogenetic
features, and CD49d-dependent interactions in lymph node and bone marrow
microenvironment responsible for growth- and survival- supporting signals,
eventually influencing CLL prognosis and therapeutic options.
PMID- 27514847
TI - Fast and improved separation of major coumarins in Ammi visnaga (L.) Lam. by
supercritical fluid chromatography.
AB - The first supercritical fluid chromatography method for the determination of five
major coumarins (dihydrosamidin, visnadin, samidin, khellin, and visnagin) in
Ammi visnaga fruits is described. Their baseline separation was possible in less
than 5 min by using a UPC2 HSS C18 SB column with 1.8 MUm particle size and a
mobile phase comprising CO2 , methanol, acetonitrile, and diethylamine. The type
of stationary phase used was of particular relevance because, except for the
selected one, the others did not resolve the two structural isomers
dihydrosamidin and visnadin. Method validation confirmed that the procedure is
linear (R2 >= 0.9996) in a concentration range from 6 to 480 MUg/mL, it is
accurate (recovery rates: 97.2-103.6%) and precise (intraday deviation <= 6.6%,
intraday deviation <= 1.7%); injecting 1 MUL of standard solution, the determined
limit of detection was below 1.9 MUg/mL for all compounds. The analysis of
different A. visnaga samples revealed their similar compositions, and khellin
(0.75-1.01%) and visnagin (0.18-0.46%) were the dominant coumarins. Visnadin and
dihydrosamidin, the individual quantification of which is described for the first
time, were present at concentrations below 0.14%.
PMID- 27514848
TI - Age-associated and tissue-specific expression of osteopontin in male Hu sheep
reproductive tract.
AB - Osteopontin (OPN) is indispensable in mammalian reproduction, but the role of OPN
in male reproductive tract and fertility remains unclear. The objective of this
study is to elucidate the function of OPN by unveiling the localization and
expression of OPN in the reproductive tract (testis, epididymis, and ductus
deferens) of male Hu sheep in different ages (10-days, 4-months, and 8-months).
To accomplish this, the localization, mRNA and protein expression patterns of OPN
in all samples were investigated. Immune staining showed that OPN was present in
the testicular interstitium of prepubertal Hu sheep testis (10-days and 4-months
group), while it was immunostained in acrosomes of spermatids nearby adluminal
compartment of seminiferous tubules in sexual maturity Hu sheep testis (8-months
group). The localization of OPN in epididymis gradually changed from the loose
connective tissue to the apical region of principal cells (pseudostratified
columnar epithelium) with growing (10-days to 8-months). In addition, increase
trend was observed in the mRNA expression levels of OPN with growing in the same
reproductive tissues (P<0.05). Furthermore, two different OPN isoforms of 30kDa
and 34kDa were detected in the reproductive tract of male Hu sheep by western
blot. Immunofluorescence detection showed that OPN was localized in the cauda
epididymal spermatozoa. These results suggested that the expression of OPN might
be closely related to spermatogenesis and spermatozoa function in Hu sheep. This
will be helpful for us to understand how OPN regulate the high reproductive
capacity in Hu sheep.
PMID- 27514849
TI - Construction and characterization of osteogenic and vascular endothelial cell
sheets from rat adipose-derived mesenchymal stem cells.
AB - In this study, adipose-derived mesenchymal stem cells (ADSCs) were isolated from
adipose tissues of rats. Flow cytometry identification showed that ADSCs of
passage 3 highly expressed CD29 and CD44, but hardly expressed CD31 and CD45.
Adipogenic, osteogenic, and chondrogenic differentiation were confirmed by the
results of oil red O staining, alkaline phosphatase (ALP), and alcian blue
staining, respectively. ADSCs at a density of 1*10(6)/cm(2) were cultured in the
osteogenic medium and the osteogenic cell sheets could be obtained after 14 d.
The cell sheets were positive with von kossa staining. The transmission electron
microscopy (TEM) result showed that needle-like calcium salt crystals were
deposited on the ECM. These results suggested that the osteogenic cell sheets may
have potential osteogenesis ability. ADSCs at a density of 1*10(6)/cm(2) were
cultured in the endothelial cell growth medium-2 and the endothelial cell sheets
can be formed after 16 d of culture. The TEM image confirmed that the Weibel
Palade corpuscle was seen in the cells. The expression of CD31 was positive,
suggesting that the endothelial cell sheets may have a strong ability to form
blood vessels. In this study, two types of cell sheets with the potential
abilities of osteogenesis and blood vessels formation were obtained by induced
culture of ADSCs in vitro, which lays a foundation to build vascularized tissue
engineered bone for the therapy of bone defects.
PMID- 27514850
TI - Engineering cell fate: Spotlight on cell-activation and signaling-directed
lineage conversion.
AB - Direct reprogramming of specialized cells into other cell types has
revolutionized the fields of stem cell, differentiation, and regenerative
medicine. Direct reprogramming technology can convert various differentiated cell
types to other fates by the forced expression of lineage-specific transcription
factors. In addition to this approach, transdifferentiation can be induced in
somatic cells by a method named cell-activation and signaling-directed (CASD)
lineage conversion, which uses pluripotency reprogramming factors in combination
with specific differentiation signals. This approach is capable of generating
tissue-specific progenitors in addition to functional mature cells through a
challenging transitory (pluripotent or non-pluripotent) state. Interestingly, the
CASD lineage conversion has been accomplished by using small molecules and growth
factors in a chemical-only paradigm. This approach will have a substantial
positive impact on the field and bring reprogramming technology into the
translational pipeline. From the regenerative medicine perspective, in future,
new therapies might be designed based on the patient's own cells that are
directly reprogrammed into the desired cell types in vitro and in situ. This
review provides an overview of direct reprogramming to different lineages and
describes what is known about the cell-activation and signaling-directed
transdifferentiation.
PMID- 27514851
TI - A systematic review of randomised control trials of sexual health interventions
delivered by mobile technologies.
AB - BACKGROUND: Sexually transmitted infections (STIs) pose a serious public health
problem globally. The rapid spread of mobile technology creates an opportunity to
use innovative methods to reduce the burden of STIs. This systematic review
identified recent randomised controlled trials that employed mobile technology to
improve sexual health outcomes. METHODS: The following databases were searched
for randomised controlled trials of mobile technology based sexual health
interventions with any outcome measures and all patient populations: MEDLINE,
EMBASE, PsycINFO, Global Health, The Cochrane Library (Cochrane Database of
Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane
Methodology Register, NHS Health Technology Assessment Database, and Web of
Science (science and social science citation index) (Jan 1999-July 2014).
Interventions designed to increase adherence to HIV medication were not included.
Two authors independently extracted data on the following elements:
interventions, allocation concealment, allocation sequence, blinding,
completeness of follow-up, and measures of effect. Trials were assessed for
methodological quality using the Cochrane risk of bias tool. We calculated effect
estimates using intention to treat analysis. RESULTS: A total of ten randomised
trials were identified with nine separate study groups. No trials had a low risk
of bias. The trials targeted: 1) promotion of uptake of sexual health services,
2) reduction of risky sexual behaviours and 3) reduction of recall bias in
reporting sexual activity. Interventions employed up to five behaviour change
techniques. Meta-analysis was not possible due to heterogeneity in trial
assessment and reporting. Two trials reported statistically significant
improvements in the uptake of sexual health services using SMS reminders compared
to controls. One trial increased knowledge. One trial reported promising results
in increasing condom use but no trial reported statistically significant
increases in condom use. Finally, one trial showed that collection of sexual
health information using mobile technology was acceptable. CONCLUSIONS: The
findings suggest interventions delivered by SMS interventions can increase uptake
of sexual health services and STI testing. High quality trials of interventions
using standardised objective measures and employing a wider range of behavioural
change techniques are needed to assess if interventions delivered by mobile phone
can alter safer sex behaviours carried out between couples and reduce STIs.
PMID- 27514853
TI - Contribution of Aspartic Proteases in Candida Virulence. Protease Inhibitors
against Candida Infections.
AB - Candida species are the major opportunistic human pathogens accounting for 70-90%
of all invasive fungal infections. Candida spp, especially C. albicans, are able
to produce and secrete hydrolytic enzymes, particularly aspartic proteases
(Saps). These enzymes production is an evolutionary adaptation of pathogens to
utilize nutrients and survive in host. Sap1-10 are believed to contribute to the
adhesion and invasion of host tissues through the degradation of cell surface
structures. Aspartic proteases control several steps in innate immune evasion and
they degrade proteins related to immunological defense (antibodies, complement
and cytokines), allowing the fungus to escape from the first line of host
defense. The existing ways to identify potential drug targets rely on specific
subset like virulence genes, transcriptional and stress response factors. Candida
virulence factors like Sap isoenzymes can be pivotal targets for drug
development. The identification of mechanism of a non-canonical inflammasome
exerted by Saps could open novel therapeutic strategies to dampen
hyperinflammatory response in candidiasis.
PMID- 27514852
TI - The catalytic subunit of magnesium-protoporphyrin IX monomethyl ester cyclase
forms a chloroplast complex to regulate chlorophyll biosynthesis in rice.
AB - KEY MESSAGE: YGL8 has the dual functions in Chl biosynthesis: one as a catalytic
subunit of MgPME cyclase, the other as a core component of FLU-YGL8-LCAA-POR
complex in Chl biosynthesis. Magnesium-protoporphyrin IX monomethyl ester (MgPME)
cyclase is an essential enzyme involved in chlorophyll (Chl) biosynthesis.
However, its roles in regulating Chl biosynthesis are not fully explored. In this
study, we isolated a rice mutant yellow-green leaf 8 (ygl8) that exhibited
chlorosis phenotype with abnormal chloroplast development in young leaves. As the
development of leaves, the chlorotic plants turned green accompanied by
restorations in Chl content and chloroplast ultrastructure. Map-based cloning
revealed that the ygl8 gene encodes a catalytic subunit of MgPME cyclase. The
ygl8 mutation caused a conserved amino acid substitution (Asn182Ser), which was
related to the alterations of Chl precursor content. YGL8 was constitutively
expressed in various tissues, with more abundance in young leaves and panicles.
Furthermore, we showed that expression levels of some nuclear genes associated
with Chl biosynthesis were affected in both the ygl8 mutant and YGL8 RNA
interference lines. By transient expression in rice protoplasts, we found that N
terminal 40 amino acid residues were enough to localize the YGL8 protein to
chloroplast. In vivo experiments demonstrated a physical interaction between YGL8
and a rice chloroplast protein, low chlorophyll accumulation A (OsLCAA).
Moreover, bimolecular fluorescence complementation assays revealed that YGL8 also
interacted with the other two rice chloroplast proteins, viz. fluorescent
(OsFLU1) and NADPH:protochlorophyllide oxidoreductase (OsPORB). These results
provide new insights into the roles of YGL8, not only as a subunit with catalytic
activity, but as a core component of FLU-YGL8-LCAA-POR complex required for Chl
biosynthesis.
PMID- 27514854
TI - General Aspects of Two-Component Regulatory Circuits in Bacteria: Domains,
Signals and Roles.
AB - All living organisms are subject to changing environments, which must be sensed
in order to respond swiftly and efficiently. Two-component systems (TCS) are
signal transduction regulatory circuits based typically on a membrane bound
sensor kinase and a cytoplasmic response regulator, that is activated through a
histidine to aspartate phosphorelay reactions. Activated response regulator acts
usually as a transcription factor. The best known examples were identified in
bacteria, but they are also found in fungi, algae and plants. Thus far, they are
not found in mammals. Regulatory circuits coupled to two-component systems
exhibit a myriad of responses to environmental stimuli such as: redox potential,
pH, specific metabolites, pressure, light and more recently to specific
antimicrobial peptides that activate a sensor kinase responsible for expressing
virulence factors through the active response regulator. In this review we
explore general aspects on two-component systems that ultimately can play a role
on virulence regulation, also the intriguing domain properties of the sensor
kinases that can be a potential target for antimicrobial compounds. Only a
handful of sensor kinases are extensively characterized, the vast majority belong
to what we call 'the dark matter of bacterial signal transduction' since no known
signal, structure and biochemical properties are available. Regulatory circuits
from vertebrate pathogenic organisms can explain virulence in terms of either
response to environmental factors or specific niche occupancy. Hopefully,
knowledge on these signal transduction systems can lead to identify novel
molecules that target two-component systems, since the increase of drug resistant
microorganisms is worrisome.
PMID- 27514856
TI - Ecosystem fluxes of hydrogen in a mid-latitude forest driven by soil
microorganisms and plants.
AB - Molecular hydrogen (H2 ) is an atmospheric trace gas with a large microbe
mediated soil sink, yet cycling of this compound throughout ecosystems is poorly
understood. Measurements of the sources and sinks of H2 in various ecosystems are
sparse, resulting in large uncertainties in the global H2 budget. Constraining
the H2 cycle is critical to understanding its role in atmospheric chemistry and
climate. We measured H2 fluxes at high frequency in a temperate mixed deciduous
forest for 15 months using a tower-based flux-gradient approach to determine both
the soil-atmosphere and the net ecosystem flux of H2 . We found that Harvard
Forest is a net H2 sink (-1.4 +/- 1.1 kg H2 ha-1 ) with soils as the dominant H2
sink (-2.0 +/- 1.0 kg H2 ha-1 ) and aboveground canopy emissions as the dominant
H2 source (+0.6 +/- 0.8 kg H2 ha-1 ). Aboveground emissions of H2 were an
unexpected and substantial component of the ecosystem H2 flux, reducing net
ecosystem uptake by 30% of that calculated from soil uptake alone. Soil uptake
was highly seasonal (July maximum, February minimum), positively correlated with
soil temperature and negatively correlated with environmental variables relevant
to diffusion into soils (i.e., soil moisture, snow depth, snow density). Soil
microbial H2 uptake was correlated with rhizosphere respiration rates (r = 0.8, P
< 0.001), and H2 metabolism yielded up to 2% of the energy gleaned by microbes
from carbon substrate respiration. Here, we elucidate key processes controlling
the biosphere-atmosphere exchange of H2 and raise new questions regarding the
role of aboveground biomass as a source of atmospheric H2 and mechanisms linking
soil H2 and carbon cycling. Results from this study should be incorporated into
modeling efforts to predict the response of the H2 soil sink to changes in
anthropogenic H2 emissions and shifting soil conditions with climate and land-use
change.
PMID- 27514855
TI - Effectiveness of rotavirus vaccines against rotavirus infection and
hospitalization in Latin America: systematic review and meta-analysis.
AB - BACKGROUND: Rotavirus was the leading cause of childhood diarrhoea-related
hospitalisations and death before the introduction of rotavirus vaccines.
METHODS: We describe the effectiveness of rotavirus vaccines to prevent rotavirus
infections and hospitalizations and the main rotavirus strains circulating before
and after vaccine introduction through a systematic review and meta-analysis of
studies published between 1990 and 2014. 203 studies were included to estimate
the proportion of infections due to rotavirus and 10 to assess the impact of the
vaccines. 41 of 46 studies in the post-vaccination period were used for meta
analysis of genotypes, 20 to calculate VE against infection, eight for VE against
hospitalisation and seven for VE against severe rotavirus-diarrhoea. RESULTS:
24.3 % (95 % CI 22.1-26.5) and 16.1 % (95 % CI 13.2-19.3) of cases of diarrhoea
were due to rotavirus before and after vaccine introduction, respectively. The
most prevalent G types after vaccine introduction were G2 (51.6 %, 95 % CI 38
65), G9 (14.5 %, 95 % CI 7-23) and G1 (14.2 %, 95 % CI 7-23); while the most
prevalent P types were P[4] (54.1 %, 95 % CI 41-67) and P[8] (33 %, 95 % CI 22
46). G2P[4] was the most frequent genotype combination after vaccine
introduction. Effectiveness was 53 % (95 % CI 46-60) against infection, 73 % (95
% CI, 66-78) against hospitalisation and 74 % (95 % CI, 68.0-78.0) against severe
diarrhoea. Reductions in hospitalisations and mortality due to diarrhoea were
observed in countries that adopted universal rotavirus vaccination. CONCLUSIONS:
Rotavirus vaccines are effective in preventing rotavirus-diarrhoea in children in
Latin America. The vaccines were associated with changes in genotype
distribution.
PMID- 27514857
TI - Danshensu Promotes Cholesterol Efflux in RAW264.7 Macrophages.
AB - Contemporary research suggests that macrophage foam cell and cholesterol efflux
defect play pivotal role in atherogenesis. We reported on the heretofore unknown
therapeutic effect of Danshensu (DSS) in reducing intracellular cholesterol level
and unraveled the mechanism of DSS promotes cholesterol efflux. Oxidized low
density lipoprotein stimulation of Raw264.7 cells into foam cells, which were
treated with DSS and co-treated with Simvastatin and Rosiglitazone. PPARgamma,
ABCA1, ABCG1, SR-BI, CD36, and LXR-alpha mRNA were quantified by Real-Time PCR.
Western blotting was used to determine protein expression of PPARgamma, ABCA1 and
CD36. Cellular cholesterol handling was studied by measurement of intracellular
lipid droplets concentration and cholesterol efflux. DSS significantly reduced
scavenger receptor CD36 and its orthologue SR-BI. In addition, DSS stimulated the
upregulation of cellular cholesterol exporters ABCA1 and ABCG1 to reduce
intracellular lipid accumulation. DSS can reduce lipid deposition in Raw264.7
foam cells by balancing CD36 and ABCA1 protein expression.
PMID- 27514858
TI - Genomic Analysis of Genes Involved in the Biosynthesis of Very Long Chain
Polyunsaturated Fatty Acids in Thraustochytrium sp. 26185.
AB - Thraustochytrium sp. 26185 is a marine protist that can produce a large amount of
docosahexaenoic acid (DHA, 22:6n-3), an omega3 very long chain polyunsaturated
fatty acid (VLCPUFA) of nutritional importance. However, the mechanism of how
this fatty acid is synthesized and assembled into the storage lipid
triacylglycerol is unclear. Here we report sequencing of the whole genome and
genomic analysis of genes involved in the biosynthesis and assembly of the fatty
acids in this species. Genome sequencing produced a total of 2,418,734,139 bp
clean sequences with about 62 fold genome coverage. Annotation of the genome
sequences revealed 10,797 coding genes. Among them, 10,216 genes could be
assigned into 25 KOG classes where 451 genes were specifically assigned to the
group of lipid transport and metabolism. Detailed analysis of these genes
revealed co-existence of both aerobic pathway and anaerobic pathways for the
biosynthesis of DHA in this species. However, in the aerobic pathway, a key gene
encoding stearate Delta9 desaturase introducing the first double bond to long
chain saturated fatty acid 18:0 was missing from the genome. Genomic survey of
genes involved in the acyl trafficking among glycerolipids showed that, unlike
plants, this protist did not possess phosphatidylcholine:diacylglycerol
cholinephosphotransferase, an important enzyme in bridging two types of
glycerolipids, diacylglycerols (DAG) and phosphatidylcholines (PtdCho). These
results shed new insight on the biosynthesis and assembly of VLCPUFA in the
Thraustochytrium.
PMID- 27514859
TI - The Effect of Tailored Web-Based Feedback and Optional Telephone Coaching on
Health Improvements: A Randomized Intervention Among Employees in the Transport
Service Industry.
AB - BACKGROUND: Lifestyle-related health problems are an important health concern in
the transport service industry. Web- and telephone-based interventions could be
suitable for this target group requiring tailored approaches. OBJECTIVE: To
evaluate the effect of tailored Web-based health feedback and optional telephone
coaching to improve lifestyle factors (body mass index-BMI, dietary intake,
physical activity, stress, sleep, tobacco and alcohol consumption, disease
history, self-perceived health, and motivation to change health habits), in
comparison to no health feedback or telephone coaching. METHODS: Overall, 3,876
employees in the Swedish transport services were emailed a Web-based
questionnaire. They were randomized into: control group (group A, 498 of 1238
answered, 40.23%), or intervention Web (group B, 482 of 1305 answered, 36.93%),
or intervention Web + telephone (group C, 493 of 1333 answered, 36.98%). All
groups received an identical questionnaire, only the interventions differed.
Group B received tailored Web-based health feedback, and group C received
tailored Web-based health feedback + optional telephone coaching if the
participants' reported health habits did not meet the national guidelines, or if
they expressed motivation to change health habits. The Web-based feedback was
fully automated. Telephone coaching was performed by trained health counselors.
Nine months later, all participants received a follow-up questionnaire and
intervention Web + telephone. Descriptive statistics, the chi-square test,
analysis of variance, and generalized estimating equation (GEE) models were used.
RESULTS: Overall, 981 of 1473 (66.60%) employees participated at baseline (men:
66.7%, mean age: 44 years, mean BMI: 26.4 kg/m(2)) and follow-up. No significant
differences were found in reported health habits between the 3 groups over time.
However, significant changes were found in motivation to change. The intervention
groups reported higher motivation to improve dietary habits (144 of 301
participants, 47.8%, and 165 of 324 participants, 50.9%, for groups B and C,
respectively) and physical activity habits (181 of 301 participants, 60.1%, and
207 of 324 participants, 63.9%, for B and C, respectively) compared with the
control group A (122 of 356 participants, 34.3%, for diet and 177 of 356
participants, 49.7%, for physical activity). At follow-up, the intervention
groups had significantly decreased motivation (group B: P<.001 for change in
diet; P<.001 for change in physical activity; group C: P=.007 for change in diet;
P<.001 for change in physical activity), whereas the control group reported
significantly increased motivation to change diet and physical activity (P<.001
for change in diet; P<.001 for change in physical activity). CONCLUSION: Tailored
Web-based health feedback and the offering of optional telephone coaching did not
have a positive health effect on employees in the transport services. However,
our findings suggest an increased short-term motivation to change health
behaviors related to diet and physical activity among those receiving tailored
Web-based health feedback.
PMID- 27514860
TI - shRNA mediated knockdown of Nav1.7 in rat dorsal root ganglion attenuates pain
following burn injury.
AB - BACKGROUND: Abnormal acute pain after burn injury still torments patients
severely. In this study, we investigated that one voltage gated sodium channel
Nav1.7 plays a vital role in lowering heat pain threshold after burn injury, and
the hypothesis that knockdown of Nav1.7 attenuates pain following burn injury.
METHODS: Sixty eight adult male Sprague-Dawley rats were divided into 4 treatment
groups: (1) sham, which hind paw was put on the room temperature metal plate for
15 s (2) burn model, which hind paw was put on the 85 degrees C metal plate for
15 s. (3) Burn injury + lentiviral vector -SCN9AsiRNA-GFP (LV- SCN9AsiRNA-GFP
group, n = 18), which receive the DRG microinjection of LV- SCN9AsiRNA-GFP on the
zero day. (4) Burn injury + lentiviral vector negative control (LV-NC-GFP group,
n = 18), which receive the DRG microinjection of empty lentiviral vector on the
zero day. RESULTS: Both mechanical and heat threshold were measured from day 1 to
21. Meanwhile, expression of sodium channels Nav1.7 in injured dorsal root
ganglia were measured on post-operative days 7(POD 7). Rats exhibited decreased
thresholds on both mechanical allodynia and thermal withdrawl latency,
accompanied by increased Nav1.7 and c-fos expression in dorsal root ganglion
(DRG). And knockdown of Nav1.7 in L5DRG led to the attenuation of burn injury
induced mechanical allodynia and thermal hyperalgesia in the rats. CONCLUSION: We
provide evidence that shRNA mediated knockdown of Nav1.7 attenuates burn induced
pain in rats as well as decreased the activiation of c-fos protein.
PMID- 27514861
TI - Preoperative simulation regarding the appropriate port location for laparoscopic
hepaticojejunostomy: a randomized study using a disease-specific training
simulator.
AB - PURPOSE: We verified the appropriate port location for laparoscopic
hepaticojejunostomy using a comprehensive laparoscopic training simulator.
METHODS: We developed a hepaticojejunostomy model, consist of common hepatic duct
and intestine and participants required to place two sutures precisely using two
different port locations (A: standard port location, B: modified port location).
The order of tasks was randomly determined using the permuted block method (Group
I: Task A -> Task B, Group II: Task B -> Task A). The time for task completion
and total number of errors were recorded. In addition, we evaluated the spatial
paths and velocity of both forceps. Statistical analyses were performed using a
statistical software program. RESULTS: The time for the task, the total error
score, and the spatial paths and velocity of both forceps were not significantly
different between groups I and II. Furthermore, the port location and order of
tasks (group I or group II) did not significantly affect the results. In
contrast, there were significant differences in the performance between experts
and novices, who were classified as such based on the total number of experienced
endoscopic surgeries. CONCLUSION: Preoperative port simulation in advanced
surgery using our artificial simulator is feasible and may facilitate minimally
invasive surgery for children.
PMID- 27514862
TI - Workshop Report: Crystal City VI-Bioanalytical Method Validation for Biomarkers.
AB - With the growing focus on translational research and the use of biomarkers to
drive drug development and approvals, biomarkers have become a significant area
of research within the pharmaceutical industry. However, until the US Food and
Drug Administration's (FDA) 2013 draft guidance on bioanalytical method
validation included consideration of biomarker assays using LC-MS and LBA, those
assays were created, validated, and used without standards of performance. This
lack of expectations resulted in the FDA receiving data from assays of varying
quality in support of efficacy and safety claims. The AAPS Crystal City VI (CC
VI) Workshop in 2015 was held as the first forum for industry-FDA discussion
around the general issues of biomarker measurements (e.g., endogenous levels) and
specific technology strengths and weaknesses. The 2-day workshop served to
develop a common understanding among the industrial scientific community of the
issues around biomarkers, informed the FDA of the current state of the science,
and will serve as a basis for further dialogue as experience with biomarkers
expands with both groups.
PMID- 27514863
TI - Assessment of fetal optic chiasm: an echoanatomic and reproducibility study.
AB - OBJECTIVES: Our aims were: (1) to perform an echoanatomic correlation study, in
order to confirm that the structure identified as the optic chiasm (OC) on
ultrasound (US) is indeed this anatomical structure; (2) to assess and compare
the reproducibility of two- (2D) and three-(3D) dimensional US in measurement of
the OC in normal fetuses; and (3) to assess whether the spatial orientation of
the OC changes with increasing gestational age. METHODS: For the echoanatomic
study, the OC was studied in a neonatal specimen, deceased at 29 + 4 weeks, by
passing a suture around the OC and visualizing the supposed OC structure on US
while pulling gently on the suture. The reproducibility study included 39 women
with normal pregnancy at 20-33 weeks undergoing routine obstetric US examination.
After the routine exam, the OC was visualized on 2D-US, and a 2D image and 3D
volume dataset were stored for offline measurement. On the 2D images, the
diameters of the OC decussation and the optic tract proximal to the transducer
were measured. For the 3D volume dataset, multiplanar image correlation with
volume contrast imaging (VCI) was used to measure both these diameters and the
chiasmocallosal angle (CCA). Two operators each took two sets of measurements of
the diameters on 2D- and 3D-US, and intra- and interoperator variability were
analyzed using Cronbach's alpha intraclass correlation coefficient (ICC), while a
single operator took two sets of CCA measurements for assessment of intraoperator
variability. Differences in CCA with increasing gestational age were also
analyzed by regression, and CCA measurements were divided into three groups
according to gestational age and their means compared by one-way ANOVA. RESULTS:
During the echoanatomic experiment, when the sling suture was pulled, the
hyperechoic X-shaped structure just below the circle of Willis identified on 2D
US as the OC was displaced slightly and was eventually cut by the sling,
confirming its identity as the OC. Intraoperator variability was low and almost
identical for the two operators and the two imaging modalities for measurement of
the decussation (ICC for 2D-US: 0.96 vs 0.95; 3D-US: 0.95 vs 0.96), but less so
for the optic tract (ICC for 2D-US: 0.95 vs 0.91; 3D-US: 0.94 vs 0.83).
Interoperator variability was low for the decussation (2D-US: 0.92; 3D-US: 0.92),
but higher for the optic tracts (ICC for 2D-US: 0.80; 3D-US: 0.78). The
difference between the mean measurement of the two operators was not
statistically significantly different for the decussation, but it was for the
optic tracts (P = 0.04). The CCA increased steadily between 20 and 30 gestational
weeks and plateaued thereafter, at least until 33 weeks. CONCLUSIONS: The
hyperechoic structure evident on 2D- and 3D-US, just below the circle of Willis,
is indeed the OC. 2D-US is apparently as good as 3D-US for visualization of the
OC. However, only measurement of the decussation showed low intra- and
interoperator variability, whereas measurement of the optic tract is of
questionable variability. As gestation advances between 20 and 30 weeks, the OC
becomes more oblique in orientation. Copyright (c) 2016 ISUOG. Published by John
Wiley & Sons Ltd.
PMID- 27514864
TI - High-intensity drinking by underage young adults in the United States.
AB - AIMS: To estimate (1) the prevalence of underage binge drinking, high-intensity
drinking and intoxication among young adults aged 19/20 years; (2) change in
these behaviors across the transition out of high school and across historical
time; and (3) associations between these behaviors and key covariates, including
college status. DESIGN, SETTING, PARTICIPANTS: Longitudinal data from the US
nationally representative Monitoring the Future study included 1657 respondents
first surveyed as 12th graders (modal age 18 years) in 2005-13 and again at modal
age 19/20 years in 2006-14. MEASUREMENTS: Self-reported measures of alcohol use,
demographics, college attendance and living situation. FINDINGS: Binge drinking
(5+ drinks on one occasion) was reported by 24.2% [95% confidence interval (CI) =
22.0, 26.5] of young adults aged 19/20; 10.3% (CI = 8.7, 11.9) reported high
intensity drinking of 10+ drinks; 4.2% (CI = 3.1, 5.2) reported 15+ drinks. Usual
moderate/high intoxication when drinking was reported by 33.1% (CI = 30.6, 35.6);
29.6% (CI = 27.2, 32.0) reported usual sustained intoxication of 3+ hours.
Significant variability (P < 0.001) in these behaviors from ages 18 to 19/20 was
observed. Significant decreases (P < 0.05) across historical time in 5+ and 10+
drinking were found. Four-year college students not residing with parents had
significantly higher odds of moderate/high intoxication, binge drinking and high
intensity drinking compared with other groups (P < 0.001). CONCLUSIONS: Young
adult underage binge drinking (5+ drinks on one occasion), high-intensity
drinking (10+ and 15+ drinks) and intoxication are relatively common in the
United States, and show meaningful variability across the transition out of high
school. Four-year college students and those who do not live with their parents
are more likely to engage in high-intensity drinking than their peers.
PMID- 27514865
TI - Electrical Impedance Tomography in A Patient with Non-Specific Interstitial
Pneumonia.
PMID- 27514866
TI - Adult-born dentate granule cells show a critical period of dendritic
reorganization and are distinct from developmentally born cells.
AB - Adult-born dentate granule cells (abGCs) exhibit a critical developmental phase
during function integration. The time window of this phase is debated and whether
abGCs become indistinguishable from developmentally born mature granule cells
(mGCs) is uncertain. We analyzed complete dendritic reconstructions from abGCs
and mGCs using viral labeling. AbGCs from 21-77 days post intrahippocampal
injection (dpi) exhibited comparable dendritic arbors, suggesting that structural
maturation precedes functional integration. In contrast, significant structural
differences were found compared to mGCs: AbGCs had more curved dendrites, more
short terminal segments, a different branching pattern, and more proximal
terminal branches. Morphological modeling attributed these differences to
developmental dendritic pruning and postnatal growth of the dentate gyrus. We
further correlated GC morphologies with the responsiveness to unilateral medial
perforant path stimulation using the immediate-early gene Arc as a marker of
synaptic activation. Only abGCs at 28 and 35 dpi but neither old abGCs nor mGCs
responded to stimulation with a remodeling of their dendritic arbor. Summarized,
abGCs stay distinct from mGCs and their dendritic arbor can be shaped by afferent
activity during a narrow critical time window.
PMID- 27514867
TI - Suspected sepsis: summary of NICE guidance.
PMID- 27514868
TI - Intraprofessional collaboration and learning between specialists and general
practitioners during postgraduate training: a qualitative study.
AB - BACKGROUND: During postgraduate training, general practitioners and other
specialists must learn how to deliver shared care to patients; however, the
development of formal intraprofessional education is often hampered by curricular
constraints. Delivering shared care in everyday work provides trainees with
opportunities for informal learning from, about and with one another. METHODS:
Twelve semi-structured interviews were undertaken with trainee general
practitioners and specialists (internal medicine or surgery). A thematic analysis
of the input was undertaken and a qualitative description developed. RESULTS:
Trainees from different disciplines frequently interact, often by telephone, but
generally they learn in a reactive manner. All trainees are highly motivated by
the desire to provide good patient care. Specialist trainees learn about the
importance of understanding the background of the patient from GPs, while GP
trainees gain medical knowledge from the interaction. Trainees from different
disciplines are not very motivated to build relationships with each other and
have fewer opportunities to do so. Supervisors can play an important role in
providing intraprofessional learning opportunities for trainees. CONCLUSIONS:
During postgraduate training, opportunities for intraprofessional learning occur,
but there is much room for improvement. For example, supervisors could increase
the involvement of trainees in collaborative tasks and create more awareness of
informal learning opportunities. This could assist trainees to learn
collaborative skills that will enhance patient care.
PMID- 27514869
TI - Idiopathic thrombotic thrombocytopenic purpura: strongest risk factor for relapse
from remission is having had a relapse.
AB - BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, episodic
clinical syndrome involving the production of thrombi in the microvasculature
accompanied by thrombocytopenia and symptoms of organ ischemia. Idiopathic TTP
develops when a patient produces antibodies that react with the protease
ADAMTS13. The course after an episode is unpredictable; patients may relapse
frequently or never. There is no laboratory value that can reliably predict
potential relapse. STUDY DESIGN AND METHODS: To assess diagnostic and predictive
values for risk of relapse, plasma samples from 27 patients with idiopathic TTP
in remission were analyzed for anti-ADAMTS13 immunoglobulin (Ig)G, ADAMTS13
activity, and ADAMTS13 inhibitor titer. Patients were recruited at the Department
of Hematology at the University Medical Center, Johannes Gutenberg University
Mainz, Mainz, Germany. RESULTS: Anti-ADAMTS13 IgG was detected in 12 patients
(44%); their median level of ADAMTS13 activity was nondetectable. Patients with
anti-ADAMTS13 IgG had a median number of three previous relapses, whereas the 15
patients without presence of IgG (56%) had a median number of one previous
relapse (p < 0.001; Mann-Whitney U test). The concentration of free anti-ADAMTS13
IgG and the levels measuring inhibitory activity (Bethesda unit) were positively
correlated. CONCLUSION: A subgroup of TTP patients in remission with anti
ADAMTS13 IgG and nondetectable ADAMTS13 activity showed an increased risk for
relapsing disease as demonstrated by their number of past relapses. The positive
correlation we observed between anti-ADAMTS13 IgG and inhibitor levels supports
the theory of ADAMTS13 inhibition as the crucial mechanism causing severe
deficiency in ADAMTS13 activity in TTP.
PMID- 27514870
TI - Renal transplant among type 1 and type 2 diabetes patients in Spain: A population
based study from 2002 to 2013.
AB - BACKGROUND: To describe trends in the rates and short-term outcomes of renal
transplants (RTx) among patients with or without diabetes in Spain (2002-2013).
METHODS: We used national hospital discharge data to select all hospital
admissions for RTx. We divided the study period into four three-year periods.
Rates were calculated stratified by diabetes status: type 1 diabetes (T1DM), type
2 diabetes (T2DM) and no-diabetes. We analyzed Charlson comorbidity index (CCI),
post-transplant infections, in-hospital complications of RTx, rejection, in
hospital mortality and length of hospital stay. FINDINGS: We identified 25,542
RTx. Rates of RTx increased significantly in T2DM patients over time (from 9.3
cases/100,000 in 2002/2004 to 13.3 cases/100,000 in 2011/2013), with higher rates
among people with T2DM for all time periods. T2DM patients were older and had
higher CCI values than T1DM and non-diabetic patients (CCI>=1, 31.4%, 20.4% and
21.5%, respectively; P<0.05). Time trend analyses showed significant increases in
infections, RTx-associated complications and rejection for all groups (all P
values<0.05). Infection rates were greater in people with T2DM (20.8%) and T1DM
(23.5%) than in non-diabetic people (18.7%; P<0.05). Time trend analyses (2002
2013) showed significant decreases in mortality during admission for RTx (OR
0.75, 95% CI 0.68-0.83). Diabetes was not associated with a higher in-hospital
mortality (OR: 1.20, 95% CI 0.92-1.55). INTERPRETATION: RTx rates were higher and
increased over time at a higher rate among T2DM patients. Mortality decreased
over time in all groups. Diabetes does not predict mortality during admission for
RTx. FUNDING: Instituto Salud Carlos III and URJC-Banco Santander.
PMID- 27514871
TI - Dehydration of lactic acid to acrylic acid over lanthanum phosphate catalysts:
the role of Lewis acid sites.
AB - Lanthanum phosphate (LaP) nano-rods were synthesized using n-butylamine as a
shape-directing agent (SDA). The resulting catalysts were applied in the
dehydration of lactic acid to acrylic acid. Aiming to understand the nature of
the active sites, the chemical and physical properties of LaP materials were
studied using a variety of characterization techniques. This study showed that
the SDA not only affected the porosity of the LaP materials but also modified the
acid-base properties. Clearly, the modification of the acid-base properties
played a more critical role in determining the catalytic performance than
porosity. An optimized catalytic performance was obtained on the LaP catalyst
with a higher concentration of Lewis acid sites. Basic sites showed negative
effects on the stability of the catalysts. Good stability was achieved when the
catalyst was prepared using the appropriate SDA/La ratio.
PMID- 27514872
TI - Communication channels to promote evidence-based practice: a survey of primary
care clinicians to determine perceived effects.
AB - BACKGROUND: Research suggests that the channels through which evidence-based
practices are communicated to healthcare professionals can shape the ways they
engage with, and use, this information. For instance, there is evidence to
suggest that information should be communicated via sources that are deemed to be
credible, like government departments, professional bodies and peers. This
article examines the contention that information should be communicated via
credible sources. More specifically, the article examines the different
communication channels through which primary care clinicians learnt of resources
on evidence-based sexual healthcare - namely, clinical aides and online training
programs. Furthermore, the article determines whether these communication
channels influenced the perceived impact of the resources. METHODS: Primary care
clinicians in Australia (n = 413), notably General Practitioners (n = 214) and
Practice Nurses (n = 217), were surveyed on the GP Project - a suite of resources
to promote evidence-based sexual healthcare within primary care. Survey items
pertained to the source of information about the resources (or communication
channel), perceived usefulness of the resources, frequency of use, subsequent
contact with the Sexual Health Infoline and a sexual health clinic, as well as
the perceived impact of the resources. To determine the relationships between the
different communication channels and the perceived impact of the resources, a one
way ANOVA using Tukey's post-hoc test, an independent sample t-test, a chi(2)
test, and a Kruskal-Wallis H test were performed where appropriate. RESULTS: Of
the respondents who were aware of the clinical aides (49.9%), the largest
proportion became aware of these through an educational event or a colleague. Of
those who were aware of the online training programs (36.9%), the largest
proportion became aware of these through a professional body or government
organisation, either directly or via their website. Although both resource types
were reported to improve clinical practice, the reported use and the perceived
impact of the resources were not influenced by the way the clinicians learnt of
the resources. CONCLUSIONS: These findings cast doubt on the suggestion that the
channels through which evidence-based practices are communicated to healthcare
professionals shape the ways they engage with, and use, this information, as well
as the perceived impact of this information. Given the importance of evidence
based practices, these curious findings suggest that the source of this
information might be of little consequence.
PMID- 27514873
TI - Ivermectin exhibits potent anti-mitotic activity.
AB - Ivermectin (IVM) is a pharmaceutical used as an anti-parasitic drug in livestock,
companion animals and humans. The primary site of action of IVM is believed to be
glutamate-gated chloride channels (GluCls). However we have recently reported a
direct interaction between IVM and nematode tubulin with micromolar affinity.
Here we report that IVM also interacts with mammalian tubulin. To test this
possibility, we used the tubulin polymerization assay and found that IVM
increased the degree of polymerization of mammalian tubulin. Furthermore when
HeLa cells were exposed to IVM it stabilized the mammalian tubulin against the
depolymerizing effects of cold temperatures, and prevented the replication of the
HeLa cells in vitro. However, the IVM-induced inhibition of HeLa cell division
was reversible. The data suggests that mammalian microtubules bound IVM and were
stabilized by IVM at micromolar concentrations. IVM may thus affect the dynamics
of tubulin polymerization and depolymerization, which in turn can result in cell
death. Given that IVM is already approved for use in humans, its development as
an anti-mitotic is a potentially appealing option.
PMID- 27514874
TI - Variations in seroprevalences of canine leishmaniasis: Could it be a consequence
of the population structure?
AB - Canine leishmaniasis is a parasitic disease caused by Leishmania infantum and is
transmitted by Phlebotominae vectors. Despite numerous publications on the
subject, some essential aspects of the epidemiology are not yet sufficiently
clear. We proposed a stochastic model with the aim of identifying some important
gaps in the current knowledge of leishmaniasis, such as the frequency of vector
infection or a dog's life expectancy depending on their purpose and their health
status. We only found that the purpose was a significant factor. Furthermore, we
detected relationships among age, gender and habitat with the dogs' purposes that
can affect the calculation of the overall seroprevalence of the analysed sample.
The development of this model will allow us to discard potential confounding
factors as gender, age, purpose or habitat.
PMID- 27514875
TI - In vitro anthelmintic activity of the Zizyphus joazeiro bark against
gastrointestinal nematodes of goats and its cytotoxicity on Vero cells.
AB - This study examined the in vitro effect of the Zizyphus joazeiro bark against
gastrointestinal nematodes of goats and its cytotoxicity on Vero cells. The
ovicidal activity of the crude hydroethanolic extract (CE), its partitioned
hexane (HE) and aqueous extract (AE) and saponins fraction (SF), including
betulinic acid (BA), a biogenetic compound from this plant found in HE, were
investigated using the inhibition of egg hatch assay (EHA). Thereafter, the
extracts and the SF were evaluated through the larval motility assay (LMA) and
larval migration inhibition assay (LMIA). The AE and SF promoted a complete
inhibition of the egg hatch, and the effective concentration to inhibit 50%
(EC50) values was 1.9 and 1.3mg/mL, respectively. The highest percentages of
inhibition in EHA observed after treatments with CE, HE and BA corresponded to
79, 48 and 17%, respectively. The extracts and SF did not show larvicidal
activity in LMA and LMIA. The AE and SF demonstrated cytotoxic effects in 3-4,5
dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide (MTT) and trypan blue tests;
however, SF was more toxic (50% inhibitory concentration, IC50=0.20mg/mL). The
chemical characterization of the SF was made through Proton Nuclear Magnetic
Resonance ((1)H NMR) and Electrospray Ionization Mass Spectrometry (ESI-MS)
analyses, which led to the identification of two saponins known as Joazeiroside B
and Lotoside A. The results obtained from the research of this saponin content
provide important information about the biological activity, especially the
anthelmintic effect present in the plant investigated. That also suggests the
types of bioactive compounds that may be responsible for this antiparasitic
activity exhibited by the plant extracts.
PMID- 27514876
TI - Chilling requirements for hatching of a New Zealand isolate of Nematodirus
filicollis.
AB - The eggs of some species of the parasitic nematode Nematodirus require a period
of chilling before they can hatch; N. filicollis is one such species. This study
investigated this requirement for chilling in a New Zealand strain of this
species. Eggs of N. filicollis were extracted from lamb's faeces and incubated at
20 degrees C to allow development to the third stage larvae within the egg. These
eggs were then placed into tissue culture plates and incubated at: 2.7 degrees C
(+/-0.99), 3.6 degrees C (+/-0.90), 4.7 degrees C (+/-0.35), 6.4 degrees C (+/
0.37), 8.0 degrees C (+/-1.54) or 9.9 degrees C (+/-0.14) for up to 224 days. At
14day intervals until day 84, then every 28 days, one plate was removed from each
temperature and placed at 13.1 degrees C (+/-0.44) for 14 days. Eggs were then
assessed for hatching. From this data, chill units were calculated by subtracting
the culture temperature from a constant threshold of 11 degrees C and multiplying
by the number of days for which the sample was cultured; then the Gompertz model
fitted. Even though hatching overall was low, a greater proportion of eggs
hatched with chill accumulation. Maximum hatching of eggs required 800-1000 chill
units. Consequently in the field, more than one season of chilling would be
required before hatching. As such a generation time could take more than one year
to complete. This is different to the hatching dynamics of N. spathiger, the
other main species found in New Zealand sheep, which does not display this
requirement for chilling and hatches immediately once the third stage larvae are
developed.
PMID- 27514877
TI - Chemical composition and in vitro activity of Calotropis procera (Ait.) latex on
Haemonchus contortus.
AB - Calotropis procera is among the species of medicinal plants that have
traditionally been used for the treatment of parasites in small ruminants,
stimulating the scientific validation of anthelmintic effects. This study aimed
to investigate the chemical composition of ethyl acetate extract of Calotropis
procera latex (EAECPL), assess the in vitro effect against Haemonchus contortus
and the structural changes caused in the adult worm. The latex was collected,
lyophilized and subjected to washing with the ethyl acetate solvent to obtain
EAECPL. The constituents of the extract were isolated by column chromatography
and identified by (13)C and (1)H nuclear magnetic resonance spectroscopy. The egg
hatching test (EHT), larval development test (LDT) and adult worms motility test
(WMT) were conducted to evaluate the effectiveness of EAECPL on eggs, larvae and
adult of H. contortus, respectively. The worms obtained from the WMT, after 24h
exposure to EAECPL or controls were observed on a scanning electron microscope
(SEM). The results were analysed by variance analysis and compared with Tukey's
test (P<0.05). Three compounds were isolated from EAECPL and identified as urs
19(29)-en-3-yl acetate, (3beta)-Urs-19(29)-en-3-ol, and 1-(2',5'-dimethoxyphenyl)
glycerol. In the EHT, EAECPL inhibited larval hatching by 91.8% at dose of
4mg/ml. In the LDT 1mg/ml inhibited 99.8% larval development. In the WMT, EAECPL
in the concentration of 100MUg/ml inhibited 100% motility of worms, 12h post
exposition. In the SEM, obvious differences were not detected between the
negative control worms and the worms treated with EAECPL. In this study, EAECPL
showed an effect on inhibition egg hatching, larval development and motility of
the adult worms of H. contortus. This should be related both to the identified
compounds, as well as the other compounds present in the EAECPL, acting alone or
synergistically.
PMID- 27514878
TI - Filarioids infecting dogs in northeastern Brazil.
AB - Species of filarial nematodes belonging to the genera Dirofilaria and
Acanthocheilonema are recognised as common parasites of dogs throughout the
world. Recently, other filarioids featured by the presence of dermal
microfilariae (e.g., Onchocerca lupi and Cercopithifilaria spp.) have been
recognised in Europe. In Brazil, reports of filarioids in dogs are limited to
Dirofilaria immitis, Acanthocheilonema reconditum and Cercopithifilaria bainae.
To investigate the distribution of filarial infections in dogs living in an
endemic region from northeastern Brazil, blood and skin samples (n=104) were
microscopically (modified Knott's test and skin snip sediment examination) and
molecularly evaluated. Twenty-two dogs (21.15%) were positive at microscopic
and/or molecular examination for at least one filarioid species, with 21 (20.19%)
animals positive for blood microfilariae at molecular and/or at microscopic
examination. Microfilariae of D. immitis were detected in 12 (11.54%) animals,
with co-infection of D. immitis and A. reconditum observed in four (3.85%)
individuals. One animal was positive for C. bainae at both microscopic and
molecular examination. Analysis of sequence obtained in the present study showed
significant alignment identity with that of C. bainae from Europe. Considering
that in the area of study arthropod vectors (mosquitoes, fleas and ticks) are
prevalent throughout the year, preventive measures should be disposed in order to
avoid the animal infestation and pathogen infection.
PMID- 27514879
TI - Microfilaricidal efficacy of a single administration of Advocate((r)) (Bayer
Animal Health) in dogs naturally infected with Dirofilaria immitis or Dirofilaria
repens.
AB - The present study evaluated the microfilaricidal efficacy of a single application
of the spot-on containing imidacloprid 10%/moxidectin 2.5% (Advocate((r)), Bayer
Animal Health) in dogs naturally infected either by Dirofilaria immitis or
Dirofilaria repens. Dogs living in north-eastern and central-southern Italy,
endemic for D. immitis and D. repens respectively, were randomly screened.
Sixteen animals, eight infected with D. immitis and eight with D. repens, and
fulfilling inclusion criteria were enrolled. Dogs infected with D. immitis
received an adulticide treatment prior to the study and Advocate((r)) 3 weeks
after. The animals were divided in blocks of two (1:1, T1:T2) animals each, where
Day 0 (D0) had an interval of 15days to compare T2 vs. T1 dogs during the first
fortnight of examination (i.e. T2 dogs acted as control animals at each
examination). At baseline (Days -15 and 0 for T2 and T1 dogs, respectively) the
animals had a range of microfilaraemia of 180-99.700mff/ml (D. immitis) and 60
750 mff/ml (D. repens). All animals received a topical administration of
Advocate((r)) at D0 and were examined for microfilariae with microscopic and
molecular tests at D15, D30, D60 and D90. All animals scored negative for mff at
the first control post-treatment and throughout the study, with the exception of
two D. immitis- infected animals that had a 2 mff/ml count at D15, and then
become negative from Day 30 onwards. No adverse events were observed. The present
study demonstrates the safety and the high microfilaricidal efficacy (99.97% and
100% for D. immitis and D. repens, respectively) of a single dose of moxidectin
contained in Advocate((r)) in naturally infected dogs.
PMID- 27514880
TI - Seroprevalence of Neospora caninum in feral swine (Sus scrofa) in the United
States.
AB - The protozoon Neospora caninum is a major cause of abortion in cattle worldwide.
Canids (Canis familiaris, Canis latrans, Canis lupus) are definitive hosts
whereas many other animal species, including pigs, are intermediate hosts for the
parasite. Between 2012 and 2014, serum samples from 1059 feral swine (Sus scrofa)
from 29 states of the USA were tested for N. caninum antibodies, using the N.
caninum agglutination test (NAT). Of these, 159 (15.0%) feral pigs from 21 states
tested positive, with a range of titers of 1:25 (cut-off) (n=153), 1:200 (1),
1:400 (1), 1:800 (3) and 1:3200 (1). Results indicate widespread exposure of
feral swine to N. caninum infection across the USA.
PMID- 27514881
TI - Efficacy of osthole for Echinococcus granulosus in vitro and Echinococcus
multilocularis in vivo.
AB - Echinococcosis is a zoonotic infection caused by cestode species of the genus
Echinococcus; in addition, this zoonosis has long been neglected as a parasitic
disease and has limited treatment options. Clinical drugs such as benzimidazole
derivatives have limited treatment efficacy. The current study evaluated a novel
drug, osthole, with low toxicity and high activity against Echinococcus in vitro
and in vivo. The results in vitro indicated that the viability of Echinococcus
granulosus protoscoleces in the group treated with osthole (120MUM) decreased by
100% within 3days. In vivo experiments were conducted using parasite-infected
mice. For this purpose, three groups of infected mice were treated daily for 6
weeks with albendazole (ABZ, 100mg/kg, positive control group), osthole
(100mg/kg, experimental group), or honey/PBS (100mg/kg, negative control group),
respectively. The osthole- and ABZ-treated groups presented a significant
reduction in wet weight of metacestodes, increase in the level of interleukin
(IL)-4 and the percentage of eosinophils compared with the control group. Osthole
exhibited a high activity against echinococcosis in vivo. In addition, the
toxicity of osthole was evaluated via an in vitro 3-(4,5)-dimethylthiahiazo(-z
y1)-3,5-di-phenytetrazoliumromide (MTT) assay, as well as via morphological
observation and calculation of liver and kidney function indexes in vivo. No
obvious toxic effects of osthole were observed in our study. Therefore, this
novel drug may be a promising alternative to benzimidazole in anti-echinococcosis
chemotherapy.
PMID- 27514882
TI - Comparison of different light sources for trapping Culicoides biting midges,
mosquitoes and other dipterans.
AB - The response of Culicoides biting midges, mosquitoes and other dipterans to
different wavelengths was evaluated in a farm meadow in northern Spain. A total
of 9449 specimens of 23 species of Culicoides, 5495 other ceratopogonids (non
biting midges), 602 culicids and 12428 other mixed dipterans were captured.
Centers for Disease Control and Prevention (CDC) suction light traps fitted with
five light emitting diodes (LEDs) (white, green, red, blue, ultraviolet) were run
for 15 consecutive nights. Significantly more Culicoides were collected in those
traps fitted with green, blue or ultraviolet (UV) lights than in red and white
baited LED traps for the most abundant species captured: C. punctatus (37.5%), C.
cataneii (26.5%) and C. obsoletus/C. scoticus (20.4%). Similar results were
obtained for non-Culicoides ceratopogonids, mosquitoes and other mixed dipterans.
Wavelengths in green (570nm) resulted effective for targeting some Culicoides
species, culicids and other midges. In a second trial, the effectiveness of 4-W
white and UV tubes was compared to traps fitted with UV LED and a standard
incandescent light bulb. More specimens of all taxa were collected with
fluorescent black light (UV) traps than with the other light sources, except
culicids, which were recovered in high numbers from fluorescent white light
traps.
PMID- 27514883
TI - Seroprevalence of Toxoplasma gondii in seabirds from Abrolhos Archipelago,
Brazil.
AB - Toxoplasma gondii is a coccidian parasite that infects almost all warm-blooded
animals, including birds. Abrolhos is an archipelago of five islands, located in
the Atlantic Ocean, 56 nautical kilometers from the south coast of the state of
Bahia, northeastern Brazil. Part of this archipelago is a National Marine Park,
which is a conservation area protected by the Brazilian government. The objective
of this study was to determine the occurrence of T. gondii antibodies in sera of
seabird's species Sula spp. and Phaeton spp. from breeding colonies located in
the Islands of Santa Barbara and Redonda, Abrolhos's archipelago. Sera were
tested by modified agglutination test, first screened at 1:5 dilution (cut-off
point) and the positive samples were titrated at a two-fold serial dilution.
Serum samples were obtained from 69 birds of four species: Sula dactylatra (23
birds), Sula leucogaster (19 birds), Phaeton aethereus (25 birds) and Phaeton
lepturus (2 birds). Antibodies to T. gondii were found in 24 (34.8%) of 69
seabirds with titers that ranged from 5 to 640. Occurrence value in S. dactylatra
was 34.8% (8/23), in S. leucogaster was 47.4% (9/19), in P. aethereus was 28%
(7/25) and the 2 P. lepturus were negative. This is the first description of T.
gondii antibodies in free ranging seabirds of the orders Suliformes and
Phaethontiformes.
PMID- 27514884
TI - Molecular characterisation of a disseminated Cryptosporidium infection in a Koi
carp (Cyprinus carpio).
AB - Cryptosporidium is a protozoan parasite that infects a wide range of hosts, yet
relatively little is known about the epidemiology of cryptosporidiosis in fish.
Here we report a disseminated Cryptosporidium infection in a male Koi carp
(Cyprinus carpio), with parasite stages identified deep within the epithelium of
the intestine, kidneys, spleen, liver and gills causing severe granulomatous
inflammatory lesions. Molecular characterization at two loci; 18S ribosomal RNA
(rRNA) and actin, revealed this to be a novel Cryptosporidium genotype, most
closely related to Cryptosporidium molnari.
PMID- 27514885
TI - Detection and quantification of Leishmania infantum in naturally and
experimentally infected animal samples.
AB - Leishmania infantum is one of the causative agents of visceral leishmaniasis
(VL). VL is the most severe form of leishmaniasis and can be fatal if it is not
properly treated. Although several PCR works are intended to detect L. infantum,
in silico analysis of available primers and/or primer-probes reveals potential
cross species amplification. Here, a TaqMan-based quantitative real time PCR
(qPCR) assay was developed for specific detection and quantitation of L. infantum
in tissue samples from experimentally or naturally infected animals, mice or
dogs, respectively. For this assay, primers and probes were designed for the
kinetoplast minicircle DNA of L. infantum. The qPCR assay achieved a detection
limit of 0.01pg of parasite DNA, and allowed specific amplification of L.
infantum in both asymptomatic and symptomatic naturally infected dogs with inter
assay variation coefficients between 0.05-0.11. There was no cross amplification
with dog DNA or with L. braziliensis, L. donovani, L. major, L. tropica or
Trypanosoma cruzi. In addition, our assay detected a significantly higher
parasite load in symptomatic than in the asymptomatic animals (p<0.0001). We
believe this approach will be a valuable tool for the specific detection of L.
infantum in regions of sympatric transmission of VL-causing parasites.
PMID- 27514886
TI - Ovicidal and larvicidal activity of extracts of Opuntia ficus-indica against
gastrointestinal nematodes of naturally infected sheep.
AB - This study describes the in vitro anthelmintic activity of extracts from Opuntia
ficus indica against gastrointestinal nematodes of sheep. The anthelmintic
activity was evaluated by inhibition of egg hatching, larval development and
larval migration assays. The residual aqueous fractions from cladodes and fruits
showed higher ovicidal activity with EC50 values of 7.2mg/mL and 1.5mg/mL,
respectively. The aqueous, hexane, and ethyl acetate fractions from fruits and
the aqueous fraction from cladodes inhibited 100% of larval development at the
lowest concentration tested (1.56mg/mL). The crude cladode and fruit ethanolic
extracts inhibited larval migration and showed EC50 values of 0.74mg/mL and
0.27mg/mL, respectively. Phytochemical screening detected high concentrations of
alkaloids, tannins, flavonoids, and saponins in the fruits and cladodes. The
results demonstrated that O. ficus exhibits anthelmintic activity in vitro,
suggesting that, beyond its nutritional potential, this plant can also be an ally
for parasite control in sheep.
PMID- 27514887
TI - Polarized M2 macrophages in dogs with visceral leishmaniasis.
AB - The objective of the present study was to analyze the skin (nasal surface and ear
regions), lymph nodes (popliteal and pre-scapular), spleen and liver of dogs with
visceral leishmaniasis (VL), in order to investigate the relationship between the
parasite load measured as DNA copy number of Alpha gene of DNA polymerase of
Leishmania infantum by quantitative PCR and the number of M2 macrophages by
immunohistochemistry. A set of 29 naturally infected dogs from an endemic area
for VL were sampled and another set of six dogs negative for VL and from a non
endemic area were analyzed as the control group (C). The spleen presented the
highest number of Leishmania DNA copies, with significant differences between the
groups G1 and G2 (with and without skin lesions, respectively). The M2 phenotype
immunostaining predominated among the macrophages in granulomas and inflammatory
infiltrates of samples from the skin, lymph nodes and spleens examined. The
presence of M2 macrophages in dogs from infected group differed significantly
from the control group, in all organs analyzed, excepted liver. The highest
proportion of M2 macrophages coincided with the highest parasitism loads found in
more susceptible organs of VL dogs, even in the skin, considered a more resistant
organ, while the liver showed low parasitism load and low immunostaining for M2
macrophages with no significant differences between infected and negative groups.
It was concluded that the predominance of M2 phenotype in VL dogs favored the
multiplication of Leishmania infantum in organs of dogs that are more susceptible
to Leishmania infection, as skin, lymph nodes and spleen.
PMID- 27514888
TI - Ascarid infestation in captive Siberian tigers in China.
AB - The Siberian tiger is endangered and is listed by the International Union for the
Conservation of Nature; the captive environment is utilized to maintain Siberian
tiger numbers. Little information regarding the prevalence of parasites in
Siberian tigers is available. A total of 277 fecal samples of Siberian tigers
were analyzed in this study. The microscopic analysis indicated the presence of
ascarid eggs of Toxascaris leonina and Toxocara cati. The ascarid infection rate
was 67.5% in Siberian tigers. The internal transcribed spacer-1 (ITS-1)
phylogenetic analysis indicated that T. leonina belonged to Toxascaris and that
Toxo. cati belonged to Toxocara. The infestation rate and intensity of T. leonina
were higher than those of Toxo. cati. One-way analysis of variance showed that
the presence of T. leonina was significantly associated with age (P<0.05).
Temperature changes also influenced T. leonina and Toxo. cati infestation, and a
rise in temperature caused an increase in the number of T. leonina and Toxo. cati
eggs. This study provides a better understanding of ascarid infestation among the
captive Siberian tigers and is helpful for the prevention of the spread of
infectious parasitic diseases among other tigers in the zoo.
PMID- 27514889
TI - Dominant fitness costs of resistance to fipronil in Musca domestica Linnaeus
(Diptera: Muscidae).
AB - House fly, Musca domestica L., (Diptera: Muscidae) a common pest of poultry, has
developed resistance to the commonly used insecticide fipronil. The life history
traits were examined in the fipronil-selected (Fipro-SEL), susceptible
counterpart (UNSEL), and their hybrid progeny strains in order to design an
effective resistant management strategy. Compared to the UNSEL strain, the Fipro
SEL was 181.94-fold resistant to fipronil. This resistance was unstable after
five generations without selection. The Fipro-SEL had a significantly longer
larval duration, lower pupal weight, lower fecundity, lower hatchability, lower
number of next generation larvae, lower intrinsic rate of population increase and
lower biotic potential than the UNSEL strain. Most fitness parameters of the
hybrid progeny were similar and significantly lower than that in the UNSEL
strain, suggesting autosomal and dominant fitness costs. Compared to the UNSEL
strain, relative the fitness of the Fipro-SEL, Hybrid1 and Hybrid2 was 0.13, 0.33
and 0.30, respectively. Fipronil resistance resulted in high fitness costs and
these fitness costs were dominant and autosomal in the Fipro-SEL strain of M.
domestica. Rotation of fipronil with other insecticides having no cross
resistance should be useful for delaying the development of resistance in M.
domestica.
PMID- 27514890
TI - Equine antibody response to larval Parascaris equorum excretory-secretory
products.
AB - Parascaris equorum is an intestinal nematode of foals and young horses that can
produce mild to severe pathology. Current diagnosis is limited to detection of
patent infections, when parasite eggs are identified during fecal examinations.
This study examined the use of larval P. equorum excretory-secretory (ES)
products in a western blot test for diagnosis of prepatent equine P. equorum
infection. Sera from adult mares negative for patent P. equorum infections, foals
prior to consuming colostrum, and P. equorum infected foals were used as controls
in this study. Study samples included sera from 18 broodmares prior to
parturition and sera from their foals throughout the process of natural
infection. Sera from study horses were examined for IgG(T) antibody recognition
of ES products. Foals naturally infected with P. equorum possessed IgG(T)
antibodies against 19kDa, 22kDa, 26kDa, and 34kDa ES products. However, passive
transfer of colostral antibodies from mares was shown to preclude the use of the
crude larval ES product-based western blot test for diagnosis of prepatent P.
equorum infections in foals.
PMID- 27514891
TI - Cross-resistance to moxidectin and ivermectin on a meat sheep farm in France.
AB - Resistance to ivermectin and moxidectin was explored by a faecal egg count
reduction test in two sheep flocks with suspected anthelmintic resistance. The
FECRT confirmed one suspicion, with a mean percentage of reduction in egg
excretion within the treated groups of 0% for ivermectin (CI 95%: -228 to 58) and
13% for moxidectin (CI 95%: -152 to 70). This was further explored by a
controlled efficacy test. An experimental infection of 18 naive lambs was set up
using infective larvae isolated from this flock (5000 L3/lamb). Compared to the
control group, abomasal worm burdens (Teladorsagia circumcincta) were reduced by
90% [CI 95%: 81.5-94.8] and 85% [CI 95%: 72.4-92.2] after ivermectin (p<0.05) and
moxidectin (p<0.05) treatment respectively. Again, compared to the control group,
there was a reduction for intestinal strongyles (Trichostrongylus colubriformis)
of 100% and 99% [CI 95%: 97.5-99.7] for ivermectin and moxidectin respectively.
No difference was found between the efficacy of moxidectin and ivermectin.
Pharmacokinetic values indicated that the strongyles were submitted to
anthelmintic concentrations usually lethal to them. This trial demonstrated the
first multiple resistance of ovine strongyles in France.
PMID- 27514892
TI - Acaricidal activity of oregano oil and its major component, carvacrol, thymol and
p-cymene against Psoroptes cuniculi in vitro and in vivo.
AB - Oregano oil possesses marked antioxidant and antimicrobial activity and is widely
applied in animal husbandry. In the present study, we aimed to investigate the
acaricidal activities of oregano oil and its major component, carvacrol, thymol
and p-cymene against Psoroptes cuniculi in vitro and in vivo. The results
revealed that oregano oil exhibited significant acaricidal effects against P.
cuniculi that were dose- and time-dependent response. In in vitro test,
concentrations of 0.05% and 0.02% (v/v) killed all of the mites within 1h and 6h,
respectively. Moreover, 0.1mg/ml (w/v) carvacrol, 0.2mg/ml (w/v) thymol and 1% p
cymene (v/v) also possessed marked acaricidal activities, and compared with the
control group, elicited mean mortalities of 84.00%, 96.00% and 66% at 24h,
respectively. The median lethal times (LT50) against P. cuniculi of the
concentrations of 0.02%, 0.01% and 0.005% (v/v) of oregano oil, thymol, carvacrol
and p-cymene were 2.171h, 11.396h, 26.102h, and 4.424h, 8.957h and 15.201h,
respectively. Meanwhile, twenty naturaly infested rabbits were used to four
homogeneity groups: negative control (without treatment), positive control
(treated with ivermectin), group treated with 1% of oregano oil and other group
with 5% of oregano oil. All the treatments were topically. After the treatment of
1% and 5% oregano oil, the P. cuniculi were completely eliminated in the rabbits,
and at the end of the test (day 20), the rabbits of all treatment groups
exhibited favorable mental and physical statuses. These results indicated that
oregano oil could be widely applied as a potential acaricidal agent in the
treatment of animal acariasis in the future.
PMID- 27514893
TI - A systematic review on the global occurrence of Taenia hydatigena in pigs and
cattle.
AB - Taenia hydatigena, a non-zoonotic tapeworm species shares the same intermediate
hosts with other Taenia zoonotic species, such as Taenia solium in pigs and
Taenia saginata in cattle. The occurrence of T. hydatigena in pigs and cattle may
cause cross-reactions in immunodiagnostic tests and therefore, complicate the
diagnosis of the zoonotic species. This study was conducted to systematically
review the data on the prevalence of T. hydatigena in pigs and cattle, with the
aim to assess the potential interference in serological diagnosis of zoonotic
Taenia spp. due to T. hydatigena infection. We searched PubMed, Web of Science,
Africa Journal Online, website http://www.google.com and article reference lists
in English, French and Vietnamese with no restriction on research time and
publication status. Eligible studies included observational studies that showed
the occurrence of T. hydatigena. Twenty-six studies, divided into two animal
groups, i.e. pigs and cattle, met the eligibility criteria for qualitative
synthesis and 17 studies were included for the meta-analysis in three continents.
T. hydatigena was found by necropsy in all included studies, which mostly were
abattoir surveys. Overall, results showed the worldwide occurrence of T.
hydatigena cysticercosis in pigs and cattle. In pigs, there was a marked higher
prevalence in Asia and South America that was 17.2% (95% CI: 10.6-26.8%) and
27.5% (CI: 20.8-35.3%), respectively, compared to a low prevalence of 3.9% (95%
CI: 1.9-7.9%) in Africa. Overall, the prevalence of T. hydatigena in cattle was
low with a mean of 1.1% (95% CI: 0.2-5.2%). These results show that
interpretation of results of sero-diagnostic tests for zoonotic Taenia species in
pigs and cattle has to take into account the prevalence of T. hydatigena
infections in different settings.
PMID- 27514894
TI - F200Y polymorphism of the beta-tubulin isotype 1 gene in Haemonchus contortus and
sheep flock management practices related to anthelmintic resistance in eastern
Amazon.
AB - The objective of the present study was to determine the frequency of the F200Y
polymorphism in the beta-tubulin isotype 1 gene of Haemonchus contortus from
various sheep flocks in eastern Amazon, and to identify management practices that
may favor the emergence of resistance to anthelmintic drugs in the same area. In
total, 305 specimens of H. contortus were collected from sheep at 12 farms
located in the state of Para. An allele-specific PCR was performed to detect the
F200Y polymorphism, and questionnaires were used to obtain information about the
farms and flocks. All genotypes were detected as follows: 31% of the parasites
were RR, 37% of the parasites were SR, and 32% were SS. The completed
questionnaires revealed that all farms employed semi-intensive farming systems,
performed suppressive anthelmintic treatment, and based their choice of drug on
cost and availability rather than on any knowledge regarding drugs that remained
effective on their property. It can thus be concluded that the SNP in codon 200
of the beta-tubulin isotype 1 gene is present in the H. contortus populations
from eastern Amazon, and that a series of management practices that favor the
emergence of anthelmintic resistance are employed on these farms.
PMID- 27514895
TI - Comparison between anthelmintic treatment strategies against Ascaridia galli in
commercial laying hens.
AB - The efficacy of a sustainable deworming strategy based on targeted treatments
(TT) against Ascaridia galli was investigated for the first time in laying hen
flocks on a Swedish commercial farm. Three experimental protocols with different
levels of treatment, e.g. targeted treatment (TT), conventional treatment (CT)
and untreated (UT), were tested in randomly allocated flocks of two different
bird hybrids. Every second week faecal egg counts (FECs) were determined from
pooled faecal materials collected on trays (20*27cm) placed for a maximum of 12h
on the litter belts. In the TT, anthelmintic administration (fenbendazole, 1mg/kg
body weight for 5days) started at 22 weeks post placement (wpp) and was repeated
twice when the pooled FECs surpassed the assigned threshold of 200 egg per gram
faeces (EPG). The CT flocks were treated once at 27wpp using the same
anthelmintic. Hens in the UT were not dewormed and served as controls.
Additionally, FECs on cloacal contents, worm fecundity and worm burdens were
determined at 19, 35 and 45wpp. None of the flocks became infected until after
16wpp. The cumulative pooled FECs at the end of the study were significantly
(p<0.01) lower in the TT compared to both CT and UT. Although repeated treatment
in the TT protocol did not affect the fecundity, a worm density-dependent
increase in fecundity was observed. Cloacal FECs and the number of adult A. galli
in TT at 35 and 45wpp were significantly lower compared to other flocks. This
study provides evidence that the TT strategy is better in terms of lower worm
burden and decreased cumulative environmental parasite egg numbers compared to CT
strategy. The TT strategy should be considered as an alternative to the CT
strategy with regard to A. galli control in commercial laying hens.
PMID- 27514896
TI - Three-year evaluation of best practice guidelines for nematode control on
commercial sheep farms in the UK.
AB - Anthelmintics are commonly used on the majority of UK commercial sheep farms to
reduce major economic losses associated with parasitic diseases. With increasing
anthelmintic resistance worldwide, several countries have produced evidence
based, best practice guidelines with an example being the UK's Sustainable
Control of Parasites in Sheep (SCOPS) initiative. In 2012, a pilot study
demonstrated that SCOPS-managed farms used fewer anthelmintic treatments than
traditionally managed farms, with no impact on lamb productivity and worm burden.
Building on these results, we collected data for three consecutive years (2012
2014) with the following aims: (1) To compare the effects of traditional and
SCOPS-based parasite management on lamb productivity and worm burden; (2) To
evaluate the effect of region and farm type on lamb productivity and worm burden;
(3) To compare the frequency and patterns of use of anthelmintic treatment on
traditional and SCOPS-managed farms. The study was carried out on 16 farms
located in the North east and the South west of England and Wales. Lamb
productivity was assessed by quantifying birth, mid-season and finish weights and
calculating daily live-weight gains and time to finish in a cohort of 40-50 lambs
on each farm. Five annual faecal egg counts were carried out on each farm to
assess worm burden. No differences in lamb productivity and worm burdens were
found between farms that adopted SCOPS guidelines and traditional farms across
the three years. However, mean infection levels increased for both the SCOPS and
the traditional groups. Lamb production was not significantly different for farm
type and region but the effect of region on infection was significant. For both
ewes and lambs, SCOPS farms carried out significantly fewer anthelmintic
treatments per year, and used fewer anthelmintic doses/animal than traditional
farms. The data suggest a trend to increasing use of anthelmintics in ewes on
traditional but not on the SCOPS farms and a decreasing use of anthelmintics in
lambs on both SCOPS and traditional farms. Across time, an increasing number of
SCOPS farmers left their ewes and lambs untreated and the reverse was true for
traditional farmers. Overall, farms implementing SCOPS guidelines used less
anthelmintic treatments and less frequently than traditionally managed farms,
without loss of animal performance or increased worm burden. Implementing SCOPS
guidelines might have economic benefits for farmers, help reduce development of
anthelmintic resistance on farms and decrease any environmental impact of
anthelmintics. Furthermore, these data suggest some important epidemiological
trends that should be investigated in long-term studies.
PMID- 27514897
TI - Vaccine potential of recombinant cathepsinL1G against Fasciola gigantica in mice.
AB - In this study, we characterized and investigated the vaccine potential of
FgCatL1G against Fasciola gigantica infection in mice. Recombinant mature
FgCatL1G (rmFgCatL1G) was expressed in Escherichia coli BL21. The vaccination was
performed in Imprinting Control Region (ICR) mice (n=10) by subcutaneous
injection with 50MUg of rmFgCatL1G combined with Freund's adjuvant. Two weeks
after the second boost, mice were infected with 15 metacercariae by the oral
route. The percents of protection of rmFgCatL1G vaccine were estimated to be
56.5% and 58.3% when compared with non vaccinated-infected and adjuvant-infected
controls, respectively. Antibodies in the immune sera of vaccinated mice were
shown by immunoblot to react with the native FgCatL1s in the extract of all
stages of parasites and rmFgCatL1H, recombinant pro - FgCatL1 (rpFgCatL1). By
immunohistochemistry, the immune sera also reacted with FgCatL1s in the caecal
epithelial cells of the parasites. The levels of IgG1 and IgG2a in the immune
sera, which are indicative of Th2 and Th1 immune responses, were also increased
with IgG1 predominating. The levels of serum glutamic oxaloacetic transaminase
(SGOT) and serum glutamic pyruvic transaminase (SGPT) in rmFgCatL1G-immunized
group showed no significant difference from the control groups, but pathological
lesions of livers in rmFgCatL1G-immunized group showed significant decrease when
compared to the control groups. This study indicates that rmFgCatL1G has a
vaccine potential against F. gigantica in mice, and this potential will be tested
in larger livestock animals.
PMID- 27514898
TI - Prospective study investigating transplacental transmission of equine
piroplasmosis in thoroughbred foals in Trinidad.
AB - Equine piroplasmosis caused by Theileria equi and Babesia caballi is endemic in
Trinidad and Tobago. Transmission occurs by ticks of the family Ixodidae. T. equi
can also be transmitted transplacentally; however transplacental transmission of
B. caballi is unknown. This study aims to investigate transplacental transmission
of equine piroplasmosis from thoroughbred mares naturally infected via the tick
vector. Whole blood and serum samples were collected from 117 mares in the fifth
month of pregnancy. Blood samples were also collected from each of their foals
(89 in total) within the first 36h of birth. Additionally, all foals were
observed for clinical signs within 30days post - partum. All samples were
examined microscopically for intra-erythrocytic piroplasms. Serum ELISA tests and
PCR analysis on whole blood were performed to determine the presence of T. equi
and B. caballi. Thirty-four (30.6%) mares and 14 (15.7%) of their foals were
seropositive for T. equi. Twenty-seven (24.3%) mares were positive for T. equi by
conventional (c) PCR. Real time (q) PCR analysis based on the ema - 1 gene
revealed that seven (8%) foals were positive for T. equi. Eighty-nine (76.1%)
mares and 38 (42.7%) foals were seropositive for B. caballi. Four (3.4%) mares
were positive for B. caballi by cPCR. Three out of the four cPCR positive mares
either had resorptions, or stillbirths for that pregnancy. From this study, there
is strong evidence that transplacental transmission of B. caballi can occur
leading to foetal losses. Six foals (7%) were positive for B. caballi by qPCR. Of
these six, four were born to B. caballi seropositive mares. In this study a foal
born of a T. equi seropositive mare was 55.7 times more likely to be
serologically positive for T. equi than a foal born to a T. equi seronegative
mare. Similarly a foal born of a B. caballi seropositive mare was 39.4 times more
likely to be serologically positive for B. caballi than a foal born to a mare
that was serologically negative for B. caballi at the fifth month of pregnancy.
This is as a result of the ingestion of colostrum containing antibodies to these
pathogens. Mares should be screened during pregnancy and their foals closely
monitored at parturition for evidence of equine piroplasmosis so that treatment
can be implemented earlier for a better prognosis.
PMID- 27514899
TI - Molecular identification of Echinococcus granulosus isolates from ruminants in
Greece.
AB - Cystic echinococcosis is a parasitic disease caused by Echinococcus granulosus, a
cestode with worldwide distribution. Data on the circulating Echinococcus
granulosus genotypes in Greek livestock is scant. The aim of the present study
was to conduct a genetic analysis of 82 Echinococcus granulosus isolates from
ruminants in Greece, including areas which until today have not been the subject
of studies. The analysis relied on a PCR assay targeting cytochrome c oxidase,
subunit 1 gene (CO1), followed by bidirectional sequence analysis of the
amplification product. Eighty (n=80) of the 82 (97.6%) isolates were allocated to
Echinococcus granulosus sensu stricto (G1-G3) and were classified in 13 distinct
haplotypes (9 common and 4 novel) with 12 polymorphic sites. The presence of the
dominant haplotype EG1 as was documented in the European populations, was
indicated in the country. Almost all regions shared the same common haplotype. In
comparison to this predominant haplotype, the number of the nucleotide changes in
all the other haplotypes ranged from 1 to 5. All nucleotide changes proved to be
transitions (A<->G or C<->T). Two fertile hydatid cysts of sheep origin in
different areas (Arkadia, Ilia) of the Peloponnese were identified as
Echinococcus canadensis (G7 genotype).
PMID- 27514900
TI - Spatial distribution and risk factors for Toxoplasma gondii seropositivity in
cattle slaughtered for human consumption in Rondonia, North region, Brazil.
AB - The present study aimed to evaluate Toxoplasma gondii seroprevalence in cattle
slaughtered for human consumption from rural properties in the state of Rondonia,
North region, Brazil; the seroprevalence was determined using indirect
immunofluorescence assays (IFATs). Additionally, spatial distribution and risk
factors associated with toxoplasmosis were also analyzed. Of the 1000 cattle
serum samples examined, 53 (5.3%) were determined to be seropositive for T.
gondii with antibody titers (IgG) >=64. In regard to results of the studied risk
factors (presence of cats, cats with free access to cattle, breeding system,
animal's gender, consumption of raw milk by humans on the property and cattle
abortion in the last 12 months) and the odds ratio (OR) of each of these factors
influencing cattle to acquire toxoplasmosis, only animals raised on a
feeder/stocker/backgrounder system presented a higher probability of being
seropositive for T. gondii (OR>=1, P=0.04) than cattle raised only in a
feeder/stocker system. There was no association between the occurrence of
reproductive problems and T. gondii seropositivity. Based on results obtained in
the Brazilian state of Rondonia, it could be concluded that the presence of cats
and their contact with cattle on each property, cattle breeding purpose and
cattle abortion in the last 12 months were not considered risk factors for T.
gondii infection in cattle. Considering that the presence of T. gondii was
detected in animals slaughtered in the state of Rondonia, consuming raw or
undercooked meat from seropositive cattle should be considered a route of
transmission of T. gondii to humans. However, the prevalence of toxoplasmosis
diagnosed in cattle from this state (5.30%) is lower than the prevalence of
toxoplasmosis observed in South, Southeast and Center-West regions of Brazil,
which may vary between 48.5% and 71.0%. The low prevalence of toxoplasmosis in
cattle is highlighted in Rondonia, which is the sixth largest state for cattle
slaughtering in Brazil and is responsible for producing 20% of all cattle meat
exported by Brazil.
PMID- 27514901
TI - Evaluation of the efficacy of monthly oral administration of afoxolaner plus
milbemycin oxime (NexGard Spectra((r)), Merial) in the prevention of adult
Spirocerca lupi establishment in experimentally infected dogs.
AB - The nematode Spirocerca lupi (Rudolphi, 1809) is widely distributed but mostly
occurs sporadically with stable populations only in certain geographic areas.
This helminth mainly infects dogs and wild canids. Primary pathology relates to
migration of third stage larvae (L3) damaging the thoracic aorta and
establishment of adults in nodules in the oesophagus. The objective of the
present study was to evaluate the efficacy of milbemycin oxime in combination
with afoxolaner (NexGard Spectra((r)), Merial), administered monthly, in
preventing establishment of adult worms after experimental infection. Two groups
consisting of eight animals each were experimentally infected with 15 L3 on Days
28, -14 and -2, respectively (45 L3 per animal in total). Group 1 dogs served as
untreated (negative) control, whereas animals in group 2 were treated with
NexGard Spectra((r)) at a minimum dose of 0.5mg/kg milbemycin oxime on Day 0 and
from then onwards every 28 days up to Day 140 (six treatment occasions).
Endoscopy was performed on Day 112 and for some animals also Day 140. Necropsy
for worm recovery and nodule/lesion scoring was performed on Day 168. All eight
animals in the control group (group 1) presented with 1-3 nodules and worm counts
ranging from 9 to 41. Six animals in the NexGard Spectra((r)) group presented
with 1-4 nodules and worm counts ranging from 1 to 5. Significantly (p<0.05)
fewer worms were collected from treated animals in the treated group (geometric
mean 1.7) versus the negative control group (geometric mean 22.0) with 92.3%
efficacy calculated. There was no significant (p>0.05) difference between groups
with reference to number of nodules in the oesophagus. However, nodules in the
control group were significantly (p<0.05) larger than those in the treated group.
Number and size of lesions in the dorsal aorta did not differ statistically
between groups 1 and 2. Because NexGard Spectra((r)) was administered 28 days
after onset of inoculation, migrating and developing L3 caused damage to the
aorta wall of animals in the treated group. Milbemycin oxime (administered as
NexGard Spectra((r))) demonstrated effectiveness in reducing infection with adult
Spirocerca lupi worms in the oesophagus.
PMID- 27514902
TI - The use of epifluorescence microscopy and fluorescent dyes for visualization of
Oxyuris equi eggs.
AB - This study presents a new method for visualization of Oxyuris equi eggs collected
by means of a clear adhesive tape applied to the perianal region of horses. The
obtained results indicate that this protocol permits a quick, easy, clear and
selective visualization of Oxyuris equi eggs even in the presence of feces and
other material. Another advantage of this method is that it can be used with
fluorescent dyes solubilized in water, which will stain biologic material without
dissolving or altering the adhesive tape and is also environmentally safe. Other
dyes currently used for staining biologic materials use organic solvents, which
may be combined with acids or bases in their formulation, preventing their use
with the tape method.
PMID- 27514903
TI - Limited sharing of tick-borne hemoparasites between sympatric wild and domestic
ungulates.
AB - Tick-borne hemoparasites (TBHs) are a group of pathogens of concern in animal
management because they are associated with a diversity of hosts, including both
wild and domestic species. However, little is known about how frequently TBHs are
shared across the wildlife-livestock interface in natural settings. Here, we
compared the TBHs of wild Grant's gazelle (Nanger granti) and domestic sheep
(Ovis aries) in a region of Kenya where these species extensively overlap. Blood
samples collected from each species were screened for piroplasm and rickettsial
TBHs by PCR-based amplification of 18S/16S ribosomal DNA, respectively. Overall,
99% of gazelle and 66% of sheep were positive for Babesia/Theileria, and 32% of
gazelle and 47% sheep were positive for Anaplasma/Ehrlichia. Sequencing a subset
of positive samples revealed infections of Theileria and Anaplasma. Sequences
sorted into seven phylogenetically distinct genotypes-two Theileria, and five
Anaplasma. With the exception of a putatively novel Anaplasma lineage from
Grant's gazelle, these genotypes appeared to be divergent forms of previously
described species, including T. ovis, A. ovis, A. bovis, and A. platys. Only one
genotype, which clustered within the A. platys clade, contained sequences from
both gazelle and sheep. This suggests that despite niche, habitat, and
phylogenetic overlap, the majority of circulating tick-borne diseases may not be
shared between these two focal species.
PMID- 27514904
TI - Which is the best phenotypic trait for use in a targeted selective treatment
strategy for growing lambs in temperate climates?
AB - Targeted selective treatment (TST) requires the ability to identify the animals
for which anthelmintic treatment will result in the greatest benefit to the
entire flock. Various phenotypic traits have previously been suggested as
determinant criteria for TST; however, the weight gain benefit and impact on
anthelmintic efficacy for each determinant criterion is expected to be dependent
upon the level of nematode challenge and the timing of anthelmintic treatment. A
mathematical model was used to simulate a population of 10,000 parasitologically
naive Scottish Blackface lambs (with heritable variation in host-parasite
interactions) grazing on medium-quality pasture (grazing density=30 lambs/ha,
crude protein=140g/kg DM, metabolisable energy=10MJ/kg DM) with an initial larval
contamination of 1000, 3000 or 5000 Teladorsagia circumcincta L3/kg DM.
Anthelmintic drenches were administered to 0, 50 or 100% of the population on a
single occasion. The day of anthelmintic treatment was independently modelled for
every day within the 121day simulation. Where TST scenarios were simulated (50%
treated), lambs were either chosen by random selection or according to highest
faecal egg count (FEC, eggs/g DM faeces), lowest live weight (LW, kg) or lowest
growth rate (kg/day). Average lamb empty body weight (kg) and the resistance (R)
allele frequency amongst the parasite population on pasture were recorded at
slaughter (day 121) for each scenario. Average weight gain benefit and increase
in R allele frequency for each determinant criterion, level of initial larval
contamination and day of anthelmintic treatment were calculated by comparison to
a non-treated population. Determinant criteria were evaluated according to
average weight gain benefit divided by increase in R allele frequency to
determine the benefit per R. Whilst positive phenotypic correlations were
predicted between worm burden and FEC; using LW as the determinant criterion
provided the greatest benefit per R for all levels of initial larval
contamination and day of anthelmintic treatment. Hence, LW was identified as the
best determinant criterion for use in a TST regime. This study supports the use
of TST strategies as benefit per R predictions for all determinant criteria were
greater than those predicted for the 100% treatment group, representing an
increased long-term productive benefit resulting from the maintenance of
anthelmintic efficacy. Whilst not included in this study, the model could be
extended to consider other parasite species and host breed parameters, variation
in climatic influences on larval availability and grass growth, repeated
anthelmintic treatments and variable proportional flock treatments.
PMID- 27514905
TI - Interaction of Trypanosoma evansi with the plasminogen-plasmin system.
AB - Trypanosoma evansi is a widely-distributed haemoflagellated parasite of
veterinary importance that infects a variety of mammals including horses, mules,
camels, buffalos, cattle and deer. It is the causal agent of a trypanosomiasis
known as Surra which produces epidemics of great economic importance in Africa,
Asia and South America. The main pathology includes an enlarged spleen with
hypertrophy of lymphoid follicles, congested lungs, neuronal degeneration and
meningoencephalitis, where migration of the parasites from the blood to the
tissues is essential. Most cells, including pathogenic cells, use diverse
strategies for tissue invasion, such as the expression of surface receptors to
bind plasminogen or plasmin. In this work, we show that T. evansi is able to bind
plasminogen and plasmin on its surface. The analysis of this binding revealed a
high affinity dissociation constant (Kd of 0.080+/-0.009MUM) and 1*10(5)
plasminogen binding sites per cell. Also a second population of receptors with a
Kd of 0.255+/-0.070MUM and 3.2*10(4) plasminogen binding sites per cell was
determined. Several proteins with molecular masses between ~18 and ~70kDa are
responsible for this binding. This parasite-plasminogen interaction may be
important in the establishment of the infection in the vertebrate host, where the
physiological concentration of available plasminogen is around 2MUM.
PMID- 27514906
TI - A simulation model to investigate interactions between first season grazing
calves and Ostertagia ostertagi.
AB - A dynamic, deterministic model was developed to investigate the consequences of
parasitism with Ostertagia ostertagi, the most prevalent and economically
important gastrointestinal parasite of cattle in temperate regions. Interactions
between host and parasite were considered to predict the level of parasitism and
performance of an infected calf. Key model inputs included calf intrinsic growth
rate, feed quality and mode and level of infection. The effects of these varied
inputs were simulated on a daily basis for key parasitological (worm burden,
total egg output and faecal egg count) and performance outputs (feed intake and
bodyweight) over a 6 month grazing period. Data from published literature were
used to parameterise the model and its sensitivity was tested for uncertain
parameters by a Latin hypercube sensitivity design. For the latter each parameter
tested was subject to a 20% coefficient of variation. The model parasitological
outputs were most sensitive to the immune rate parameters that affected overall
worm burdens. The model predicted the expected larger worm burdens along with
disproportionately greater body weight losses with increasing daily infection
levels. The model was validated against published literature using graphical and
statistical comparisons. Its predictions were quantitatively consistent with the
parasitological outputs of published experiments in which calves were subjected
to different infection levels. The consequences of model weaknesses are discussed
and point towards model improvements. Future work should focus on developing a
stochastic model to account for calf variation in performance and immune
response; this will ultimately be used to test the effectiveness of different
parasite control strategies in naturally infected calf populations.
PMID- 27514908
TI - Anode macrostructures influence electricity generation in microbial fuel cells
for wastewater treatment.
AB - Microbial fuel cells (MFCs) are devices that exploit microbes for generating
electricity from organic substrates, including waste biomass and wastewater
pollutants. MFCs have the potential to treat wastewater and simultaneously
generate electricity. The present study examined how anode macrostructure
influences wastewater treatment, electricity generation and microbial communities
in MFCs. Cassette-electrode MFCs were equipped with graphite-felt anodes with
three different macrostructures, flat-plate (FP), vertical-fin (VF), and
horizontal-fin (HF) structures (these were composed of a same amount of graphite
felt), and were continuously supplied with artificial wastewater containing
starch as the major organic constituent. Polarization analyses revealed that MFCs
equipped with VF and HF anodes generated 33% and 21% higher volumetric power
densities, respectively, than that of MFCs equipped with FP anodes. Organics were
also more efficiently removed from wastewater in MFCs with VF and HF anodes
compared to reactors containing FP anodes. In addition, pyrosequencing of PCR
amplified 16S rRNA gene fragments from microbial samples collected from the
anodes showed that the presence of fins also affected the bacterial compositions
in anode biofilms. Taken together, the findings presented here suggest that the
modification of anodes with fins improves organics removal and electricity
generation in MFCs. The optimization of anode macrostructure therefore appears to
be a promising strategy for improving MFC performance without additional material
costs.
PMID- 27514907
TI - New alkalophilic beta-galactosidase with high activity in alkaline pH region from
Teratosphaeria acidotherma AIU BGA-1.
AB - A beta-d-galactosidase exhibiting high activity in the alkaline pH region was
purified from Teratosphaeria acidotherma AIU BGA-1, which we previously isolated
as a unique fungal producer of three acidophilic and one alkalophilic beta-d
galactosidases (Isobe et al., J. Biosci. Bioeng., 116, 171-174, 2013). The enzyme
was stable in the pH range 7.5-10.0 and exhibited optimal activity at pH 8.0 and
60 degrees C. The enzyme hydrolyzed 2-nitrophenyl beta-d-galactopyranoside, 4
nitrophenyl beta-d-galactopyranoside, and lactose, and the Km values were
estimated to be 0.349 mM, 0.488 mM, and 701 mM, respectively. Chelating reagents
(EDTA and o-phenanthroline) and metals (Cu2+and Ni2+) inhibited the enzyme
activity, and Mn2+ was a good activator. The enzyme also exhibited
transgalactosylation activity for lactose. The enzyme's molecular mass was
estimated to be 180 kDa, and its structure was monomeric. Thus, the enzymatic and
physicochemical characteristics of the alkalophilic beta-galactosidase in this
study clearly differed from those of the previously known alkalophilic beta-d
galactosidases.
PMID- 27514909
TI - Paper-based colorimetric biosensor for antibiotics inhibiting bacterial protein
synthesis.
AB - Due to the presence of antibiotics in environmental water and their potential
influence on the occurrence of antibiotic-resistant bacteria, development of a
detection method suitable for the screening of environmental water for
antibiotics is required. In this study, we developed a simple colorimetric paper
based biosensor based on a novel principle for the detection of antibiotics
inhibiting bacterial protein synthesis, including aminoglycosides, tetracycline,
chloramphenicol, and macrolides. This biosensor is based on the detection of a
color change induced by beta-galactosidase, which is synthesized on freeze-dried
paper discs containing an in vitro transcription/translation system. When a water
sample without antibiotics is applied to the paper discs, beta-galactosidase can
be synthesized, and it hydrolyzes a colorimetric substrate, resulting in a color
change from yellow to purple. By contrast, in the presence of antibiotics, the
color change can be hampered due to an inhibition of beta-galactosidase
synthesis. We investigated the effect of the incubation temperature and pH of
water samples and confirmed that the paper discs showed the color change to
purple in the ranges of 15-37 degrees C and pH 6-10. We observed concentration
dependent color variations of the paper discs by the naked eye and further
estimated detection limits to be 0.5, 2.1, 0.8, and 6.1 MUg/mL for paromomycin,
tetracycline, chloramphenicol, and erythromycin, respectively, using digitized
pictures. The paper-based biosensor proved to detect 0.5 MUg/mL paromomycin,
spiked in real environmental water samples, by the naked eye.
PMID- 27514910
TI - Undernutrition among adults in India: the significance of individual-level and
contextual factors impacting on the likelihood of underweight across sub
populations.
AB - OBJECTIVE: To investigate the extent to which individual-level as well as macro
level contextual factors influence the likelihood of underweight across adult sub
populations in India. DESIGN: Population-based cross-sectional survey included in
India's National Health Family Survey conducted in 2005-06. We disaggregated into
eight sub-populations. SETTING: Multistage nationally representative household
survey covering 99 % of India's population. SUBJECTS: The survey covered 124 385
females aged 15-49 years and 74 369 males aged 15-54 years. RESULTS: A social
gradient in underweight exists in India. Even after allowing for wealth status,
differences in the predicted probability of underweight persisted based upon
rurality, age/maturity and gender. We found individual-level education lowered
the likelihood of underweight for males, but no statistical association for
females. Paradoxically, rural young (15-24 years) females from more educated
villages had a higher likelihood of underweight relative to those in less
educated villages; but for rural mature (>24 years) females the opposite was the
case. Christians had a significantly lower likelihood of underweight relative to
other socio-religious groups (OR=0.53-0.80). Higher state-level inequality
increased the likelihood of underweight across most population groups, while
neighbourhood inequality exhibited a similar relationship for the rural young
population subgroups only. Individual states/neighbourhoods accounted for 5-9 %
of the variation in the prediction of underweight. We found that rural young
females represent a particularly highly vulnerable sub-population. CONCLUSIONS:
Economic growth alone is unlikely to reduce the burden of malnutrition in India;
accordingly, policy makers need to address the broader social determinants that
contribute to higher underweight prevalence in specific demographic subgroups.
PMID- 27514911
TI - Implementation of the cross-border healthcare directive in Poland: How not to
encourage patients to seek care abroad?
AB - In October 2014, after over 12 months of delay, Poland finally implemented
directive 2011/24/EU on the application of patients' rights in cross-border
healthcare. The implementing legislation in the area of cost reimbursement and
prior authorization is very restrictive. The goal is to either defer the public
payer's expenses into the future or to discourage patients from seeking care
abroad or from seeking care altogether. The Polish government and the Ministry of
Health, the key stakeholders in the implementation process, seemed to overlook
the potential monetary benefits that the implementation of the directive could
bring, for example, by promoting Poland as a destination for health tourism.
Other stakeholders, such as patients and healthcare providers, had no real
influence on the policy process. So far, the number of applications for planned
treatment abroad has been very low and the majority of them were actually turned
down as they did not meet the formal requirements. This number is likely to
remain low in the future as accessing such care is cumbersome and not affordable
for many patients. Overall, while the directive does not aim to encourage
patients to seek cross-border healthcare, the current national regulations in
Poland do not seem to facilitate access to cross-border healthcare, which is the
main goal of the directive.
PMID- 27514912
TI - Methods for Studying Ciliary Import Mechanisms.
AB - Cilia and flagella are microtubule-based organelles that play important roles in
human health by contributing to cellular motility as well as sensing and
responding to environmental cues. Defects in cilia formation and function cause a
broad class of human genetic diseases called ciliopathies. To carry out their
specialized functions, cilia contain a unique complement of proteins that must be
imported into the ciliary compartment. In this chapter, we describe methods to
measure the permeability barrier of the ciliary gate by microinjection of
fluorescent proteins and dextrans of different sizes into ciliated cells. We also
describe a fluorescence recovery after photobleaching (FRAP) assay to measure the
entry of ciliary proteins into the ciliary compartment. These assays can be used
to determine the molecular mechanisms that regulate the formation and function of
cilia in mammalian cells.
PMID- 27514913
TI - Targeting of ASH Domain-Containing Proteins to the Centrosome.
AB - A growing number of studies have used new generation technologies to characterize
the protein constituents of cilia and centrosomes. This has led to the
identification of a vast number of candidate ciliary or centrosomal proteins,
whose subcellular localization needs to be investigated and validated. Here, we
describe a simple and inexpensive method for analyzing the subcellular
localization of candidate cilium- or centrosome-associated proteins, and we
illustrate the utility as well as the pitfalls of this method by applying it to a
group of ASH (ASPM, SPD-2, Hydin) domain-containing proteins, previously
predicted to be cilia- or centrosome-associated proteins based on bioinformatic
analyses. By generating plasmids coding for epitope-tagged full-length (FL) or
truncated versions of the ASH domain-containing proteins TRAPPC8, TRAPPC13,
NPHP4, and DLEC1, followed by expression and quantitative immunofluorescence
microscopy (IFM) analysis in cultured human telomerase-immortalized retinal
pigmented epithelial (hTERT-RPE1) cells, we could confirm that TRAPPC13 and NPHP4
are highly enriched at the base of primary cilia, whereas DLEC1 seems to
associate specifically with motile cilia. Results for TRAPPC8 were inconclusive
since epitope-tagged TRAPPC8 fusion proteins were unstable/degraded in cells,
emphasizing the need for combining IFM analysis with western blotting in such
studies. The method described should be applicable to other candidate ciliary or
centrosomal proteins as well.
PMID- 27514914
TI - Morphological and Functional Characterization of the Ciliary Pocket by Electron
and Fluorescence Microscopy.
AB - In many vertebrate cell types, the proximal part of the primary cilium is
positioned within an invagination of the plasma membrane known as the ciliary
pocket. Recent evidence points to the conclusion that the ciliary pocket
comprises a unique site for exocytosis and endocytosis of ciliary proteins, which
regulates the spatiotemporal trafficking of receptors into and out of the cilium
to control its sensory function. In this chapter, we provide methods based on
electron microscopy, 3D reconstruction of fluorescence images as well as live
cell imaging suitable for investigating processes associated with endocytosis at
the ciliary pocket.
PMID- 27514915
TI - Methods to Study Interactions Between Ciliogenesis and Autophagy.
AB - Autophagy is a catabolic pathway for the degradation and recycling of
intracellular components, contributing to maintain cell homeostasis. Changes in
autophagy activity can be monitored by a variety of biochemical and functional
assays that should be used in combination. Recently, it has been described that
signaling from the primary cilium modulates autophagy. This novel and reciprocal
interaction will impact diverse aspects of the cell biology in healthy and
pathophysiological conditions. Here, we describe methods to monitor autophagy
activity in cilia mutants, as well as the use of autophagy mutants to monitor
ciliogenesis.
PMID- 27514916
TI - Recombinant Reconstitution and Purification of the IFT-B Core Complex from
Chlamydomonas reinhardtii.
AB - Eukaryotic cilia and flagella are assembled and maintained by intraflagellar
transport (IFT), the bidirectional transport of proteins between the ciliary base
and tip. IFT is mediated by the multi-subunit IFT complex, which simultaneously
binds cargo proteins and the ciliary motors. So far 22 subunits of the IFT
complex have been identified, but insights into the biochemical architecture and
especially the three-dimensional structure of this machinery are only starting to
emerge because of difficulties in obtaining homogeneous material suitable for
structural analysis. Here, we describe a protocol for the purification and
reconstitution of a complex containing nine Chlamydomonas reinhardtii IFT
proteins, commonly known as the IFT-B core complex. In our hands, this protocol
routinely yields several milligrams of pure complex suitable for structural
analysis by X-ray crystallography and single-particle cryo-electron microscopy.
PMID- 27514918
TI - A FRAP-Based Method for Monitoring Molecular Transport in Ciliary Photoreceptor
Cells In Vivo.
AB - The outer segment of rod and cone photoreceptor cells represents a highly
modified primary sensory cilium. It renews on a daily basis throughout lifetime
and effective vectorial transport to the cilium is essential for the maintenance
of the photoreceptor cell function. Defects in molecules of transport modules
lead to severe retinal ciliopathies. We have recently established a fluorescence
recovery after photobleaching (FRAP)-based method to monitor molecular
trafficking in living rodent photoreceptor cells. We irreversibly bleach the
fluorescence of tagged molecules (e.g. eGFP-Rhodopsin) in photoreceptor cells of
native vibratome sections through the retina by high laser intensity. In the
laser scanning microscope, the recovery of the fluorescent signal is monitored
over time and the kinetics of movements of molecules can be quantitatively
ascertained.
PMID- 27514917
TI - Methods for Studying Movement of Molecules Within Cilia.
AB - The assembly of cilia and eukaryotic flagella (interchangeable terms) requires
the import of numerous proteins from the cell body into the growing organelle.
Proteins move into and inside cilia by diffusion and by motor-based
intraflagellar transport (IFT). Many aspects of ciliary protein transport such as
the distribution of unloading sites and the frequency of transport can be
analyzed using direct in vivo imaging of fluorescently tagged proteins. Here, we
will describe how to use total internal reflection fluorescence microcopy (TIRFM)
to analyze protein transport in the flagella of the unicellular alga
Chlamydomonas reinhardtii, a widely used model for cilia and cilia-related
disease.
PMID- 27514919
TI - Kymographic Analysis of Transport in an Individual Neuronal Sensory Cilium in
Caenorhabditis elegans.
AB - Intraflagellar Transport (IFT) is driven by molecular motors that travel upon
microtubule-based ciliary axonemes. In the single-celled alga Chlamydomonas
reinhardtii, movement of a single anterograde IFT motor, heterotrimeric kinesin
II, is required to generate two identical motile flagella. The function of this
canonical anterograde IFT motor is conserved among all eukaryotes, yet
multicellular organisms can generate cilia of diverse structures and functions,
ranging from simple threadlike non-motile primary cilia to the elaborate cilia
that make up rod and cone photoreceptors in the retina. An emerging theme is that
additional molecular motors modulate the canonical IFT machinery to give rise to
differing ciliary morphologies. Therefore, a complete understanding of the
trafficking of ciliary receptors, as well as the biogenesis, maintenance,
specialization, and function of cilia, requires the characterization of motor
molecules.Here, we describe in detail our method for measuring the motility of
proteins in cilia or dendrites of C. elegans male-specific CEM ciliated sensory
neurons using time-lapse microscopy and kymography of green fluorescent protein
(GFP)-tagged motors, receptors, and cargos. We describe, as a specific example,
OSM-3::GFP puncta moving in cilia, but also include (Fig. 1) with settings that
have worked well for us measuring movement of heterotrimeric kinesin-II, IFT
particles, and the polycystin TRP channel PKD-2.
PMID- 27514920
TI - Visualization and Manipulation of Cilia and Intraciliary Calcium in the Zebrafish
Left-Right Organizer.
AB - Cilia play a key role in the determination of the left-right axis in vertebrates
by generating and sensing flow of extraembryonic fluid at the left-right
organizer (LRO). Perception of cilia-directed flow triggers a calcium signaling
cascade which originates within the cilium itself and then is relayed into the
surrounding mesendodermal tissue, thereby directing organ situs via the nodal
pathway. Two types of cilia, motile and immotile, function simultaneously to
coordinate and direct asymmetric intraciliary calcium signaling cues in the LRO.
Here, we describe tools, reagents, and methodologies for the visualization and
manipulation of both cilia types as well as intraciliary calcium signaling in the
LRO of zebrafish.
PMID- 27514921
TI - Methods for Studying Ciliary-Mediated Chemoresponse in Paramecium.
AB - Paramecium is a useful model organism for the study of ciliary-mediated chemical
sensing and response. Here we describe ways to take advantage of Paramecium to
study chemoresponse.Unicellular organisms like the ciliated protozoan Paramecium
sense and respond to chemicals in their environment (Van Houten, Ann Rev Physiol
54:639-663, 1992; Van Houten, Trends Neurosci 17:62-71, 1994). A thousand or more
cilia that cover Paramecium cells serve as antennae for chemical signals, similar
to ciliary function in a large variety of metazoan cell types that have primary
or motile cilia (Berbari et al., Curr Biol 19(13):R526-R535, 2009; Singla V,
Reiter J, Science 313:629-633, 2006). The Paramecium cilia also produce the motor
output of the detection of chemical cues by controlling swimming behavior.
Therefore, in Paramecium the cilia serve multiple roles of detection and
response.We present this chapter in three sections to describe the methods for
(1) assaying populations of cells for their behavioral responses to chemicals
(attraction and repulsion), (2) characterization of the chemoreceptors and
associated channels of the cilia using proteomics and binding assays, and (3)
electrophysiological analysis of individual cells' responses to chemicals. These
methods are applied to wild type cells, mutants, transformed cells that express
tagged proteins, and cells depleted of gene products by RNA Interference (RNAi).
PMID- 27514922
TI - STED and STORM Superresolution Imaging of Primary Cilia.
AB - The characteristic lengths of molecular arrangement in primary cilia are below
the diffraction limit of light, challenging structural and functional studies of
ciliary proteins. Superresolution microscopy can reach up to a 20 nm resolution,
significantly improving the ability to map molecules in primary cilia. Here we
describe detailed experimental procedure of STED microscopy imaging and dSTORM
imaging, two of the most powerful superresolution imaging techniques.
Specifically, we emphasize the use of these two methods on imaging proteins in
primary cilia.
PMID- 27514923
TI - CLEM Methods for Studying Primary Cilia.
AB - CLEM (correlated light and electron microscope) imaging is a highly useful
technique for examining primary cilia. With CLEM, it is possible to determine the
distribution of tagged proteins along the ciliary membrane and axoneme with high
precision. Scanning electron microscopy (SEM) permits measurement of ciliary
length and orientation in relation to nearby cellular structures in a 3D image;
in optimal cases, this can be combined with superresolution microscopy of
selected ciliary components as they enter or leave the cilium. This chapter
discusses CLEM methods. In the method described in detail, samples are completely
processed for sequential fluorescence and SEM observation. This method is ideal
for robust antibody localization and minimizes image manipulation in correlating
the fluorescent and SEM images. Alternative methods prepare samples for
fluorescence imaging followed by processing for SEM then observation in the SEM.
This method is ideal for optimal fluorescence imaging, particularly live cell
imaging.
PMID- 27514924
TI - Methods for Visualization of Neuronal Cilia.
AB - Neuroscientists have been captivated by cilia ever since these slender,
microtubule-based projections on the cell body were found to play critical roles
in neuronal specification, maintenance, and function. In mammals, the most common
cilia marker, acetylated alpha-tubulin, is extremely difficult to detect in
neuronal cilia. Here, we describe methods to detect neuronal cilia in culture, in
fixed sections, and in vivo, taking advantage of transgenic mice carrying
fluorescently tagged cilia proteins.
PMID- 27514925
TI - Methods to Study Centrosomes and Cilia in Drosophila.
AB - Centrioles and cilia are highly conserved eukaryotic organelles. Drosophila
melanogaster is a powerful genetic and cell biology model organism, extensively
used to discover underlying mechanisms of centrosome and cilia biogenesis and
function. Defects in centrosomes and cilia reduce fertility and affect different
sensory functions, such as proprioception, olfaction, and hearing. The fly
possesses a large diversity of ciliary structures and assembly modes, such as
motile, immotile, and intraflagellar transport (IFT)-independent or IFT-dependent
assembly. Moreover, all the diverse ciliated cells harbor centrioles at the base
of the cilia, called basal bodies, making the fly an attractive model to better
understand the biology of this organelle. This chapter describes protocols to
visualize centrosomes and cilia by fluorescence and electron microscopy.
PMID- 27514926
TI - Analysis of Axonemal Assembly During Ciliary Regeneration in Chlamydomonas.
AB - Chlamydomonas reinhardtii is an outstanding model genetic organism for study of
assembly of cilia. Here, methods are described for synchronization of ciliary
regeneration in Chlamydomonas to analyze the sequence in which ciliary proteins
assemble. In addition, the methods described allow analysis of the mechanisms
involved in regulation of ciliary length, the proteins required for ciliary
assembly, and the temporal expression of genes encoding ciliary proteins.
Ultimately, these methods can contribute to discovery of conserved genes that
when defective lead to abnormal ciliary assembly and human disease.
PMID- 27514927
TI - Planaria as a Model System for the Analysis of Ciliary Assembly and Motility.
AB - Planarian flatworms are carnivorous invertebrates with astounding regenerative
properties. They have a ventral surface on which thousands of motile cilia are
exposed to the extracellular environment. These beat in a synchronized manner
against secreted mucus thereby propelling the animal forward. Similar to the
nematode Caenorhabditis elegans, the planarian Schmidtea mediterranea is easy to
maintain in the laboratory and is highly amenable to simple RNAi approaches
through feeding with dsRNA. The methods are simple and robust, and the level of
gene expression reduction that can be obtained is, in many cases, almost total.
Moreover, cilia assembly and function is not essential for viability in this
organism, as animals readily survive for weeks even with the apparent total
absence of this organelle. Both genome and expressed sequence tag databases are
available and allow design of vectors to target any desired gene of choice.
Combined, these feature make planaria a useful model system in which to examine
ciliary assembly and motility, especially in the context of a ciliated epithelium
where many organelles beat in a hydrodynamically coupled synchronized manner. In
addition, as planaria secrete mucus against which the cilia beat to generate
propulsive force, this system may also prove useful for analysis of mucociliary
interactions. In this chapter, we provide simple methods to maintain a planarian
colony, knockdown gene expression by RNAi, and analyze the resulting animals for
whole organism motility as well as ciliary architecture and function.
PMID- 27514928
TI - Spontaneous myonecrosis in chronic myeloid leukaemia.
PMID- 27514929
TI - Reclassification of Amycolicicoccus subflavus as Hoyosella subflava comb. nov.
and emended descriptions of the genus Hoyosella and Hoyosella altamirensis.
AB - 16S rRNA gene sequences of two type strains belonging to different genera within
the suborder Corynebacterineae, namely Hoyosella altamirensis and Amycolicicoccus
subflavus, show a similarity of 99.8 %. Therefore, in order to clarify their
taxonomic relationship, a polyphasic recharacterization under the same conditions
was carried out. The peptidoglycan of H. altamirensis NBRC 109631T and A.
subflavus NBRC 109087T was of A1gamma type with meso-diaminopimelic acid as their
diagnostic diamino acid. Both strains contained MK-8 as the only detected
menaquinone, C16 : 0 and C18 : 1omega9c as the major fatty acids, and
diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol as the
principal polar lipids. The coincidences of these chemotaxonomic features
suggested that H. altamirensis and A. subflavus should be assigned to the same
genus. Meanwhile, the average nucleotide identity value between both strains and
the results of physiological and biochemical tests indicated that H. altamirensis
and A. subflavus should be affiliated to different species. Therefore, according
to Rules 38 and 41a of the Bacteriological Code, it is proposed that
Amycolicicoccus subflavus Wang et al. 2010 be reclassified as Hoyosella subflava
comb. nov. (type strain DQS3-9A1T=CGMCC 4.3532T=DSM 45089T=JCM 17490T=NBRC
109087T) and the descriptions of the genus HoyosellaJurado et al. 2009 and
Hoyosella altamirensisJurado et al. 2009 are emended accordingly.
PMID- 27514930
TI - Reduced Graphene Oxide Membranes for Ultrafast Organic Solvent Nanofiltration.
AB - Solvated reduced graphene oxide (S-rGO) membranes are stable in organic solvents,
and strong acidic, alkaline, or oxidative media. They show high rejections to
small molecules with charges the same as that of S-rGO coatings or neutral
molecules larger than 3.4 nm, while retaining their high permeances to organic
solvents.
PMID- 27514931
TI - Acute and long-term outcomes of percutaneous balloon aortic valvuloplasty for the
treatment of severe aortic stenosis.
AB - OBJECTIVES: This study aimed to evaluate the indications, short- and long-term
outcomes of balloon aortic valvuloplasty (BAV) in patients with severe aortic
stenosis (AS). METHODS: A cohort of 112 patients with AS underwent 114 BAV
procedures between October 2012 and July 2015 in two Polish interventional
cardiology centers. Clinical and echocardiographic data were prospectively
collected within 1, 6, and 12 months follow-up. RESULTS: BAV was performed as a
bridge to TAVI (51.8%), surgical aortic valve replacement (AVR, 5.4%), before
urgent noncardiac surgery (8.0%), for symptom relief (33.0%) and cardiogenic
shock (1.8%). Periprocedural, in-hospital, 1-, 6-, 12-month mortality were 2.7%;
8.9%; 8.9%; 16.9%; 22.3%, respectively. Serious periprocedural adverse events
occurred in 18.8% of patients. After the procedure, mean aortic valve area (AVA)
increased from 0.59 +/- 0.18 to 0.82 +/- 0.24 cm2 , mean peak aortic valve
gradient (pAVG) decreased from 94.0 +/- 27.6 to 65.4 +/- 20.0 mm Hg, mean aortic
gradient decreased from 58.0 +/- 17.8 to 40.5 +/- 14.6 mm Hg, P < 0.05 for all.
Left ventricular ejection fraction (LVEF) increased from median (interquartile
range) of 53.5 (30 - 64) to 60 (45 - 65)% after 1 month (P < 0.05). In patients
with impaired left ventricle function (LVEF <40%), LVEF significantly improved
(median increase of 16%) after 1 and 6 months (P < 0.05). At 12 months patients
had higher AVA, pAVG, and LVEF as compared to baseline (P < 0.05). CONCLUSIONS:
BAV is a useful procedure in high-risk AS patients, where achieved effects can be
sufficient in bridging patients for TAVI/AVR. (c) 2016 Wiley Periodicals, Inc.
PMID- 27514932
TI - European evidence-based (S3) guideline for the treatment of acne - update 2016 -
short version.
PMID- 27514933
TI - Methods report on the development of the European evidence-based (S3) guideline
for the treatment of acne - update 2016.
PMID- 27514934
TI - Comparative transcriptome analysis of basal and zygote-located tip regions of
peanut ovaries provides insight into the mechanism of light regulation in peanut
embryo and pod development.
AB - BACKGROUND: Peanut zygotes typically divide a few times to form a pre-embryo
before further embryonic development halts under normal day/night photoperiods.
Ovary elongation, however, continuesforming a downward growing peg-like
structure. When the peg is buried in the soil, embryo development resumes in the
darkness. The embryo-located region (ER) of the peg begins to enlarge and form a
pod, while the basal region (BR) of the peg has a distinct fate. The molecular
mechanisms governing these unique embryo development processes are unknown.
RESULTS: In this study, histological analysis demonstrated that from 4 days after
pollination to 3 days after soil penetration, the peanut pre-embryo remained
morphologically similar. By 9 days after soil penetration, the embryo had changed
to a globular embryo. Transcriptome analysis revealed differentially expressed
genes in the ER and BR before and after peg soil penetration. In addition to
light signaling and plant hormone metabolism genes, we identified differentially
expressed genes in the ER that contribute to embryo development and pod formation
processes, including MADS-box transcription factors, xyloglucan
endotransglucosylase/hydrolase protein, cellulose synthase, homeobox-leucine
zipper (HD-Zip) protein family genes, amino acid permease, and seed growth and
embryo morphogenesis regulators (DA1, TCP3, and YABBY). CONCLUSIONS: A large
number of genes were found to be differentially expressed in the ER and BR across
three developmental peg stages. Exact changes in gene expression were also
identified in the ER during early embryo and pod development. This information
provides an expanded knowledgebase for understanding the mechanisms of early
peanut pod formation.
PMID- 27514935
TI - PI(4,5)P2 Is Translocated by ABCA1 to the Cell Surface Where It Mediates
Apolipoprotein A1 Binding and Nascent HDL Assembly.
AB - RATIONALE: The molecular mechanism by which ATP-binding cassette transporter A1
(ABCA1) mediates cellular binding of apolipoprotein A-I (apoA1) and nascent high
density lipoprotein (HDL) assembly is not well understood. OBJECTIVE: To
determine the cell surface lipid that mediates apoA1 binding to ABCA1-expressing
cells and the role it plays in nascent HDL assembly. METHODS AND RESULTS: Using
multiple biochemical and biophysical methods, we found that apoA1 binds
specifically to phosphatidylinositol (4,5) bis-phosphate (PIP2). Flow cytometry
and PIP2 reporter-binding assays demonstrated that ABCA1 led to PIP2
redistribution from the inner to the outer leaflet of the plasma membrane.
Enzymatic cleavage of cell surface PIP2 or decreased cellular PIP2 by knockdown
of phosphatidylinositol-5-phosphate 4-kinase impaired apoA1 binding and
cholesterol efflux to apoA1. PIP2 also increased the spontaneous solubilization
of phospholipid liposomes by apoA1. Using site-directed mutagenesis, we found
that ABCA1's PIP2 and phosphatidylserine translocase activities are independent
from each other. Furthermore, we discovered that PIP2 is effluxed from cells to
apoA1, where it is associated with HDL in plasma, and that PIP2 on HDL is taken
up by target cells in a scavenger receptor-BI-dependent manner. Mouse plasma PIP2
levels are apoA1 gene dosage-dependent and are >1 MUM in apoA1 transgenic mice.
CONCLUSIONS: ABCA1 has PIP2 floppase activity, which increases cell surface PIP2
levels that mediate apoA1 binding and lipid efflux during nascent HDL assembly.
We found that PIP2 itself is effluxed to apoA1 and it circulates on plasma HDL,
where it can be taken up via the HDL receptor scavenger receptor-BI.
PMID- 27514936
TI - Testing the impact of local alcohol licencing policies on reported crime rates in
England.
AB - BACKGROUND: Excessive alcohol use contributes to public nuisance, antisocial
behaviour, and domestic, interpersonal and sexual violence. We test whether
licencing policies aimed at restricting its spatial and/or temporal availability,
including cumulative impact zones, are associated with reductions in alcohol
related crime. METHODS: Reported crimes at English lower tier local authority
(LTLA) level were used to calculate the rates of reported crimes including
alcohol-attributable rates of sexual offences and violence against a person, and
public order offences. Financial fraud was included as a control crime not
directly associated with alcohol abuse. Each area was classified as to its
cumulative licensing policy intensity for 2009-2015 and categorised as 'passive',
low, medium or high. Crime rates adjusted for area deprivation, outlet density,
alcohol-related hospital admissions and population size at baseline were analysed
using hierarchical (log-rate) growth modelling. RESULTS: 284 of 326 LTLAs could
be linked and had complete data. From 2009 to 2013 alcohol-related violent and
sexual crimes and public order offences rates declined faster in areas with more
'intense' policies (about 1.2, 0.10 and 1.7 per 1000 people compared with 0.6,
0.01 and 1.0 per 1000 people in 'passive' areas, respectively). Post-2013, the
recorded rates increased again. No trends were observed for financial fraud.
CONCLUSIONS: Local areas in England with more intense alcohol licensing policies
had a stronger decline in rates of violent crimes, sexual crimes and public order
offences in the period up to 2013 of the order of 4-6% greater compared with
areas where these policies were not in place, but not thereafter.
PMID- 27514937
TI - Levodopa/carbidopa intestinal gel therapy for advanced Parkinson Disease: AN
early toxic effect for small nerve fibers?
AB - INTRODUCTION: Peripheral neuropathy related to levodopa/carbidopa intestinal gel
(LCIG) therapy for advanced Parkinson disease (PD) is under investigation and is
debated in the literature. The purpose of the study was to detect whether small
nerve fibers are damaged during LCIG infusion. METHODS: Five advanced PD patients
were enrolled prior to starting LCIG infusion. Six PD patients on oral levodopa
(LD) treatment and 6 PD patients naive to LD were also enrolled. Clinical
examination, the Quantitative Sensory Testing battery testing, nerve conduction
studies, and intraepidermal nerve fiber density examinations were collected at
baseline and at 3, 6, and 12 months after LCIG infusion was started in the study
cohort. RESULTS: After 3, 6, and 12 months, severe skin denervation and increased
thermal thresholds were observed in the LCIG group. CONCLUSIONS: Significant
damage to small nerve fibers was detected in PD patients soon after LCIG infusion
had started, suggesting careful monitoring of small fiber impairment during LCIG
is needed. Muscle Nerve, 2016 Muscle Nerve 54: 970-972, 2016.
PMID- 27514938
TI - Usefulness of plain radiography for assessing hypouricemic treatment response in
patients with tophaceous gout.
AB - AIM: To investigate whether plain radiography is useful for assessing the changes
in gouty tophi size following hypouricemic therapy. METHODS: Gout was diagnosed
according to the American College of Rheumatology criteria. Before and after
hypouricemic treatment, serum uric acid level was measured, and plain radiography
was performed to measure gouty tophi size. The tophi were graded by measuring the
maximum vertical and horizontal diameters, and they were scored by adding up the
scores of the grades. The vertical diameter was measured on both sides of the
proximal phalanges (PPs). The horizontal diameter was measured on the lateral
side of the PPs. The maximum vertical diameter measurement was graded 0-4. The
maximum horizontal diameter measurement was graded 0-3. RESULTS: Seven hundred
first metatarsal phalangeal joints (MTPJ) of 350 patients with gout were assessed
for gouty tophi. Tophi were observed using plain radiography in 174 MTPJs (24.9%)
of 109 patients (31.1%). Follow-up plain radiography was performed in 60 of these
patients. Before the treatment, the average serum uric acid level of these
patients was 8.3 +/- 1.9 mg/dL, and the average tophi score was 3.7 +/- 2.5.
After hypouricemic treatment, the uric acid level decreased to 5.9 +/- 1.6 mg/dL
(P < 0.05), and the average tophi score decreased to 1.5 +/- 1.8 (P < 0.05).
CONCLUSIONS: This new method for measuring gouty tophi using plain radiography
may be useful for evaluating changes in gouty tophi size following hypouricemic
treatment.
PMID- 27514939
TI - 3D implementation of the symbol nomenclature for graphical representation of
glycans.
PMID- 27514940
TI - Feasibility of Intraoperative Extubation in Pediatric Heart Transplantation.
AB - Based on described benefits of fast-tracking and early extubation in children
undergoing congenital heart surgery, we applied this concept to selected children
following uncomplicated orthotopic heart transplantation (OHT). In this case
series, we report four patients who were extubated immediately after surgery in
the operating room. A mild respiratory acidosis and hypercapnia were noted on the
initial arterial blood gases, were well tolerated, and were normalized within 6
to 12 hours. There was no mortality among patients who were extubated in the
operating room, and no patients required reintubation. We conclude that operating
room extubation is feasible in selected patients undergoing OHT.
PMID- 27514941
TI - Adolescent Femoroacetabular Impingement: Gender Differences in Hip Morphology.
AB - PURPOSE: To compare the hip morphology of adolescent male patients and female
patients who underwent hip arthroscopy for femoroacetabular impingement (FAI) and
determine if gender differences exist. METHODS: We retrospectively reviewed the
records of 177 adolescents, aged 13 to 18 years, who were treated for FAI with
hip arthroscopy. We examined and analyzed preoperative magnetic resonance imaging
(MRI) scans and plain radiographs, measuring the lateral center-edge angle,
Tonnis angle, and alpha angle. The intraclass correlation coefficient between
readers was calculated. We created multiple linear regression models
incorporating age, gender, and body mass index (BMI) with the radiographic
measurements. Intraoperative findings using the Outerbridge grading system, as
well as procedure performed, were documented. We compared these findings with our
preoperative imaging measurements using the chi2 test and the Wilcoxon rank sum
test. RESULTS: The intraclass correlation coefficient showed moderate to strong
agreement between the 3 image readers. The BMI- and age-adjusted mean alpha angle
was higher in male patients than female patients on both plain radiographs (55.9
degrees vs 45.2 degrees , P < .0001) and axial oblique MRI scans (54.1 degrees
vs 42.5 degrees , P < .0001). An alpha angle greater than 55 degrees was found
in 38.9% of male patients compared with only 1% of female patients (P < .0001).
The lateral center-edge angle and Tonnis angle on MRI scans and plain radiographs
displayed no statistically significant differences between genders after we
controlled for BMI and age. Male patients were more likely to have chondral
damage intraoperatively than female patients (56.3% vs 32.5%, P = .0041).
CONCLUSIONS: Distinct differences between genders were seen both on preoperative
imaging and at the time of hip arthroscopy. We found that male patients with FAI
displayed a larger mean alpha angle, and therefore a more severe cam-type
deformity, than female patients. Our study also found that male patients were
more likely to show evidence of chondral damage than female patients at the time
of surgery. LEVEL OF EVIDENCE: Level IV.
PMID- 27514942
TI - Return to Play of Rugby Players After Anterior Cruciate Ligament Reconstruction
Using Hamstring Autograft: Return to Sports and Graft Failure According to Age.
AB - PURPOSE: To assess return to play and the frequencies of graft failure in rugby
players after anterior cruciate ligament (ACL) reconstruction using a hamstring
autograft augmented with an artificial ligament and to compare outcomes between
rugby players aged <20 and >=20 years over the long term. METHODS: A consecutive
series of 146 rugby players who underwent ACL reconstruction with a hamstring
autograft augmented with an artificial ligament were retrospectively reviewed.
The study population was further divided into 2 groups aged <20 years and >20
years and compared. RESULTS: Twenty-five patients could not be followed up, and
121 (83%) were evaluated. Most patients (90%, <20 years; 92%, >=20 years)
returned to play after ACL reconstruction. At an average follow-up period of 56.5
months, 16% of the patients sustained an ACL graft rupture. Regarding age, <20
years (n = 58, 48%) and >=20 years (n = 63, 52%), younger players had a
significantly higher failure rate (23% vs 5%, respectively; P = .006) and a
shorter time to failure (22.8 +/- 13.2 vs 35.4 +/- 15.4 months, respectively; P =
.006) than older players. CONCLUSIONS: Rugby players were likely to return to
play after ACL reconstruction with a hamstring autograft. However, there was a
higher risk of graft failure in younger players than in older players. On the
basis of this study, we conclude that the hamstring autograft may not be an
appropriate graft source to use in a younger active population, including rugby
players. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
PMID- 27514943
TI - Knotless Suture Anchor With Suture Tape Quadriceps Tendon Repair Is
Biomechanically Superior to Transosseous and Traditional Suture Anchor-Based
Repairs in a Cadaveric Model.
AB - PURPOSE: To compare the biomechanical properties of a knotless suture anchor with
suture tape quadriceps tendon repair technique with transosseous and suture
anchor repair techniques. METHODS: Twenty matched pairs of cadaveric knees
underwent a quadriceps tendon avulsion followed by repair via the use of
transosseous tunnels with #2 high-strength sutures, 5.5-mm biocomposite fully
threaded suture anchors with #2 high-strength sutures, or 4.75-mm biocomposite
knotless suture anchors with suture tape. Ten knees were repaired via
transosseous repair and 10 via fully threaded suture anchor repair, and their
matched specimens were repaired with suture tape and knotless anchors.
Biomechanical analysis included displacement during cyclic loading over 250
cycles, construct stiffness, ultimate load to failure, and failure mode analysis.
RESULTS: Compared with transosseous repairs, quadriceps tendons repaired with
knotless suture tape demonstrated significantly less displacement during cyclic
loading (cycles 1-20 3.6 +/- 1.3 vs 6.3 +/- 1.9 mm, P = .003; cycles 20-250 2.0
+/- 0.4 vs 3.1 +/- 0.9 mm, P = .011), improved construct stiffness (67 +/- 25 vs
26 +/- 12 N/mm, P = .001), and greater ultimate load to failure (616 +/- 149 vs
413 +/- 107 N, P = .004). Our repair technique also demonstrated improved
biomechanical parameters compared with fully threaded suture anchor repair in
initial displacement during cyclic loading (cycles 1-20 3.0 +/- 0.8 vs 5.1 +/-
0.9 mm, P < .001), construct stiffness (62 +/- 20 vs 28 +/- 10 N/mm, P = .001)
and ultimate load to failure (579 +/- 129 vs 399 +/- 87 N, P = .006).
CONCLUSIONS: Repair of quadriceps tendon ruptures with this knotless suture
anchor with suture tape repair technique is biomechanically superior in cyclic
displacement, construct stiffness, and ultimate load to failure compared with
transosseous and fully threaded suture anchor techniques in cadaveric specimens.
CLINICAL RELEVANCE: The demonstration that our repair technique is
biomechanically superior to previously described techniques in a cadaveric
setting suggests that consideration should be given to this technique.
PMID- 27514944
TI - Behavioural biomarkers of typical Rett syndrome: moving towards early
identification.
AB - The dynamic course of Rett syndrome (RTT) is still said to begin with a period of
apparently normal development although there is mounting evidence that
individuals with RTT show behavioural peculiarities and abnormalities during
their infancy. Their spontaneous general movements are abnormal from birth
onwards. Normal cooing vocalisation and canonical babbling (if at all required)
are interspersed with abnormalities such as proto-vowel and proto-consonant
alternations produced on ingressive airstream, breathy voice characteristics, and
pressed or high-pitched vocalisations. The gestural repertoire is limited.
Certain developmental motor and speech-language milestones are not at all
acquired or show a significant delay. Besides abnormal blinking, repetitive
and/or long lasting tongue protrusion, and bizarre smiling, there are already the
first body and/or hand stereotypies during the first year of life. We are
currently on a promising way to define a specific set of behavioural biomarkers
pinpointing RTT.
PMID- 27514945
TI - Metabolomics in cardiovascular medicine: Not personalised, not diagnostic.
PMID- 27514946
TI - Treatment for hepatitis C virus infection in India: Promising times.
PMID- 27514947
TI - The changing face of community-acquired methicillin-resistant Staphylococcus
aureus.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of
infection, both in hospitalised patients with significant healthcare exposure and
in patients without healthcare risk factors. Community-acquired methicillin
resistant S. aureus (CA-MRSA) are known for their rapid community transmission
and propensity to cause aggressive skin and soft tissue infections and community
acquired pneumonia. The distinction between the healthcare-associated (HA)-MRSA
and CA-MRSA is gradually fading owing to the acquisition of multiple virulence
factors and genetic elements. The movement of CA-MRSA strains into the nosocomial
setting limits the utility of using clinical risk factors alone to designate
community or HA status. Identification of unique genetic characteristics and
genotyping are valuable tools for MRSA epidemiological studies. Although the
optimum pharmacotherapy for CA-MRSA infections has not been determined, many CA
MRSA strains remain broadly susceptible to several non-beta-lactam antibacterial
agents. This review aimed at illuminating the characteristic features of CA-MRSA,
virulence factors, changing clinical settings and molecular epidemiology,
insurgence into the hospital settings and therapy with drug resistance.
PMID- 27514948
TI - Endemic Indian clones of Klebsiella pneumoniae-harbouring New Delhi metallo-beta
lactamase-1 on a hybrid plasmid replicon type: A case of changing New Delhi
metallo-beta-lactamase plasmid landscapes in India?
AB - PURPOSE: blaNDM genes are MBL genes that confer resistance to carbapenems.
Globally, they are associated with diverse clones and plasmids. In this study, we
characterised three isolates of Klebsiella pneumoniae-harbouring blaNDM1 from
patients undergoing chronic haemodialysis and renal transplantation. MATERIALS
AND METHODS: 3 blaNDM1 -producing K. pneumoniae were isolated from end-stage
renal disease patients undergoing haemodialysis and renal transplantation from a
nephrology unit. All the three isolates were screened for clinically relevant
resistant genes. Plasmid replicon content was analysed by polymerase chain
reaction based replicon typing. Conjugation assays were done using azide
resistant Escherichia coli J53 as the recipient strain. Multilocus sequence
typing and variable number tandem repeat typing were done to find the clonality.
Replicon sequence based typing was attempted to find the diversity of replicon
associated sequences in IncHI3 plasmids. RESULTS: All the 3 blaNDM positive
isolates possessed the New Delhi metallo-beta-lactamase-1 (NDM-1) allele with an
IncHI3 plasmid which was not transferable in one isolate. The isolates were found
to be sequence type 14 (ST14; 2 nos) and ST38 both of which were previously
reported to be the NDM-producing K. pneumoniae STs prevalent in India. Replicon
sequence analysis revealed limited sequence diversity within the repHI3 and
repFIB locus. CONCLUSION: To the best of our knowledge, this is the first report
of IncHI3, a newly assigned enterobacterial plasmid incompatibility group from
India. This could either be a case of importation or a widely circulating NDM
plasmid type in India.
PMID- 27514949
TI - Scrub typhus and spotted fever among hospitalised children in South India:
Clinical profile and serological epidemiology.
AB - BACKGROUND: Rickettsial infections are re-emerging. In India, they are now being
reported from several areas where they were previously unknown. OBJECTIVES: The
objective of this study was to describe the epidemiology, clinical profile and
outcome of serologically-confirmed scrub typhus and spotted fever among children
in a tertiary care hospital in Bengaluru. MATERIALS AND METHODS: Hospitalised
children aged <18 years, with clinical features suggestive of rickettsial disease
admitted between January 2010 and October 2012 were included prospectively.
Diagnosis was based on scrub typhus and spotted fever-specific IgM and IgG by
enzyme-linked immunosorbent assay (ELISA). RESULTS: Of 103 children with clinical
features suggestive of rickettsial illness, ELISA test confirmed 53 cases for
scrub typhus, 23 cases for spotted fever group and 14 with mixed infection. The
average age was 7.3 (+/-3.9) years and 44 (71.0%) children were male. Majority of
cases were from Karnataka (50%), Andhra Pradesh (32.3%) and Tamil Nadu (17.7%).
Common clinical features included fever (100%, average duration 11 days), nausea
and vomiting (44%), rash (36%); eschar was rare. Compared to the ELISA test, Weil
Felix test (OX-K titre of 1:80) had a sensitivity and specificity of 88.7% and
43.9%, respectively. Treatment with chloramphenicol or doxycycline was given to
the majority of the children. Complications included meningoencephalitis (28%),
shock (10%), retinal vasculitis (10%) and purpura fulminans (7%). CONCLUSIONS:
These findings suggest that the burden of rickettsial infection among children in
India is high, with a substantially high complication rate. Rickettsial-specific
ELISA tests can help in early diagnosis and early institution of appropriate
treatment that may prevent life-threatening complications.
PMID- 27514950
TI - Human leucocyte antigen Class I and II alleles associated with anti-hepatitis C
virus-positive patients of North India.
AB - PURPOSE: Humans are the only known natural hosts of hepatitis C virus (HCV). This
study was undertaken to examine the frequencies of human leucocyte antigens
(HLAs) Class I and Class II genotype profiles in anti-HCV-infected patients of
Northern India. MATERIALS AND METHODS: From a period of January 2013 to August
2014, 148 anti-HCV-positive patients of North India referred to the Department of
Molecular Biology and Transplant Immunology, Indraprastha Apollo Hospitals, New
Delhi, for performing HLA typing were included in the study. RESULTS: AFNx0102,
AFNx0131 allele frequency decreased significantly in anti-HCV-positive patients.
Frequencies for HLA-B loci did not reach any statistical significance. Among the
Class II alleles, HLA-DRB1FNx0103 and HLA-DRB1FNx0110 were significantly higher
in the patient population, and HLA-DRB1FNx0115 was significantly decreased in the
patient population as compared to the controls. CONCLUSION: HLA-AFNx0133 was
significantly increased as compared to control population and showed geographic
variation in HCV-infected individuals of India.
PMID- 27514951
TI - Distribution of Class II integrons and their contribution to antibiotic
resistance within Enterobacteriaceae family in India.
AB - BACKGROUND: Integrons are the main contributors to the development of multidrug
resistance (MDR) among Gram-negative bacilli. There is a lack of knowledge about
the molecular relation between gene cassettes and antibiotic resistance in India.
OBJECTIVE: In this study, we have investigated the occurrence of Class II
integron and their cassette array among Enterobacteriaceae. MATERIALS AND
METHODS: A total of 268 MDR non-duplicate strains of Enterobacteriaceae were
collected from Silchar Medical College and Hospital, Silchar, Assam, India,
during June 2012 to May 2013. Polymerase chain reaction was performed for
detection of the integrase genes and gene cassettes within the Class II integron
which were further analysed by sequencing. RESULTS: Class II integron was
observed in 47 isolates. Four different gene cassette arrangements were detected:
dfrA1-sat2-aadA1; dfrA1-sat2-aadA1-orfX-ybeA-ybfA-ybfB-ybgA; dfrA12-sat2-aadA1;
and dfrA1-linF-aadA1. The most prevalent cassette combination was dfrA1-sat2
aadA1. This study has also identified a set of gene cassette associated with linF
gene instead of sat2 gene. CONCLUSION: Further investigation is required to
determine the current situation and important reservoir of Class II integron for
the transmission of drug resistance among Enterobacteriaceae and their
contribution to antimicrobial resistance in hospital environment .
PMID- 27514952
TI - Identification, antifungal resistance profile, in vitro biofilm formation and
ultrastructural characteristics of Candida species isolated from diabetic foot
patients in Northern India.
AB - PURPOSE: Diabetic foot ulcers are a serious cause of diagnostic and therapeutic
concern. The following study was undertaken to determine the fungal causes of
diabetic foot ulcers, with their phenotypic and genotypic characterisation.
MATERIALS AND METHODS: A total of 155 diabetic foot ulcers were studied for 1
year. Deep tissue specimen was collected from the wounds, and crushed samples
were plated on Sabouraud dextrose agar with chloramphenicol (0.05 g).
Identification was done by growth on cornmeal agar, germ tube formation and
urease test. For molecular identification, conserved portion of the 18S rDNA
region, the adjacent internal transcribed spacer 1 (ITS1) and a portion of the
28S rDNA region were amplified, using the ITS1 and ITS2 primers. Antifungal
susceptibility against voriconazole, fluconazole and amphotericin B was
determined by standard broth microdilution method. Biofilm formation was studied
in three steps. First, on the surface of wells of microtiter plates followed by
quantification of growth by fungal metabolism measurement. Finally, biofilms were
analysed by scanning electron microscopy (SEM). RESULTS: Fungal aetiology was
found in 75 patients (48.38%). All were identified as Candida species (100%). The
prevalence of different species was Candida tropicalis (34.6%), Candida albicans
(29.3%), Candida krusei (16.0%), Candida parapsilosis (10.6%), Candida glabrata
(9.33%). All were susceptible to amphotericin B (100%). On microtiter plate, all
the isolates were viable within 48 h showing biofilms. The metabolic activity of
cells in the biofilm increased with cellular mass, especially in the first 24 h.
On SEM, majority showed budding yeast form. CONCLUSION: Non-albicans Candida spp.
with potential biofilm forming ability are emerging as a predominant cause of
diabetic foot ulcers.
PMID- 27514953
TI - Presence of viable Mycobacterium leprae in environmental specimens around houses
of leprosy patients.
AB - PURPOSE: Leprosy is a chronic systemic infectious disease caused by Mycobacterium
leprae, one of the first organisms to be established as the cause for disease in
humans. Because of high prevalence pockets of leprosy in the endemic regions, it
is necessary to identify the possible sources of M. leprae in the environment and
its mode of transmission. MATERIALS AND METHODS: Slit skin smears (SSSs) from
lesions were collected in 70% ethanol from 50 leprosy cases staying in the
leprosy resettlement village and hospital from a high endemic area. One hundred
and sixty soil samples were collected from different areas around the leprosy
hospital and from the resettlement village of cured leprosy patients where active
cases also resided at the time of sample collection. M. leprae specific gene
region (RLEP 129 bp) and 16S rRNA targets were used for polymerase chain reaction
(PCR) based detection for the presence and viability of M. leprae. An rpoT region
was also amplified to determine presence of numbers of 6 bp tandem repeats.
RESULTS: All the SSS samples collected from patients showed three copies of rpoT
region (6 bp tandem repeat, an ancient Indian type). Fifty-two soil samples
showed presence of M. leprae DNA whereas M. leprae specific 16S rRNA gene was
amplified in sixteen of these samples. PCR amplification and fragment length
analysis showed 91 bp, i.e., three copies of the rpoT 6 bp tandem repeats from
soil samples and similar three copies observed in patient samples. CONCLUSION:
Presence of viable M. leprae in the soil having same rpoT genotype of M. leprae
noted in patients suggests that it could be the same strain of M. leprae. M.
leprae found in the soil could be the one that is excreted out by the patient.
Significance of its viability in the environment and its pathogenicity with
respect to transmission needs to be further explored. Findings of this study
might provide possible insights for further exploration into understanding
transmission patterns in leprosy and also will throw light on identifying
potential for existence of extra human source or reservoirs of M. leprae, if any.
PMID- 27514954
TI - Loop-mediated isothermal amplification assay for detection of Mycobacterium
tuberculosis complex in infertile women.
AB - BACKGROUND: Female genital tuberculosis (FGTB) has a profound impact on the
reproductive health of patients including infertility. Conventional diagnostic
techniques have low sensitivity and specificity as well as long turnaround time.
There is a need of developing newer, rapid and practically adaptable technique,
especially in low-income countries. OBJECTIVE: To standardize and evaluate loop
mediated isothermal amplification (LAMP) technique for diagnosis of FGTB.
METHODS: A total of 300 endometrial biopsy samples from infertile females were
subjected to Ziehl-Neelsen (ZN) staining, Lowenstein-Jensen culture, automated
culture (BACTEC mycobacterial growth indicator tube), histopathological
examination (HPE), nucleic acid amplification by polymerase chain reaction (PCR)
and LAMP technique. Composite gold standard (either smear/culture/HPE/PCR
positive) was considered for calculation of outcome parameters. RESULTS: The
observed sensitivities of ZN smear, culture, HPE, PCR and LAMP were 2.94%,
10.29%, 8.82%, 95.59% and 66.18%, respectively. Overall concordance between PCR
and LAMP was 63%, which shows a good agreement. CONCLUSION: This study is the
first to evaluate LAMP in the diagnosis of FGTB and found it to be a rapid and
convenient technique, especially in low resource endemic settings.
PMID- 27514955
TI - Prevalence of high-risk human papilloma virus types and cervical smear
abnormalities in female sex workers in Chandigarh, India.
AB - PURPOSE: Cervical cancer is the most common cancer among women in developing
nations. Nearly 90% of the cases have been linked to the presence of high-risk
human papillomavirus (hrHPV) types 16 and 18. The risk of cervical cancer may be
high in female sex workers (FSWs) due to multiple sexual partners. This study
aimed to determine the prevalence of cytological abnormalities and hrHPV types 16
and 18 in FSWs in Chandigarh, North India using the liquid-based cytology (LBC)
approach. MATERIALS AND METHODS: The cervical brush samples were collected from
120 FSW and 98 age-matched healthy controls (HCs). These were subjected to pap
smear using conventional method, LBC and the detection of hrHPV types 16 and 18
was carried out using polymerase chain reaction. RESULTS: The LBC samples showed
better cytological details and also reduced the number of unsatisfactory smears
from 11% in Pap to 1.5% in the LBC. A significantly higher number of inflammatory
smears were reported in FSWs (51.7% vs. 34.7%, P = 0.01). The hrHPV types 16/18
were detected in 33/120 (27.5%) FSW versus 23/98 (23.5%) HCs. The risk of
acquiring hrHPV was higher in FSWs, who had age at first sex <=25 years, higher
income and the habit of smoking. CONCLUSION: The high prevalence of hrHPV among
FSWs and HCs suggests the need for the implementation of effective National
Screening Programme for early detection of hrHPV types to decrease the burden of
cervical cancer, especially in high-risk population.
PMID- 27514956
TI - Association of interleukin-28B rs12979860 and rs8099917 polymorphisms with
sustained viral response in hepatitis C virus genotype 1 and 3 infected patients
from the Indian subcontinent.
AB - BACKGROUND: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) have been
shown to impact treatment responses in hepatitis C virus (HCV) infected patients.
The association of these polymorphisms with sustained viral response (SVR) has
been studied in HCV genotype 3 infected patients in India, but not in genotype 1.
OBJECTIVES: This study aimed to determine the association of IL28B gene
polymorphisms and other host and viral factors with treatment response in
patients with HCV genotype 1 and 3 infection. MATERIALS AND METHODS: DNA from 42
HCV-infected patients on antiviral therapy was analysed for the IL28B
polymorphisms using polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP). Bidirectional sequencing was performed on a subset of
samples for verification of PCR-RFLP results. Information on age, weight, height,
diabetic status, pre-treatment viral load and alanine aminotransferase (ALT)
levels was obtained from clinical records. The IL28B genotypes and the other
factors were analysed for their association with SVR. RESULTS: The frequency
distribution of rs12979860 CC/CT/TT genotypes was found to be 66.7%, 26.2% and
7.1%, respectively. For rs8099917 genotype, the TT/GT/GG distribution was 73.8%,
21.4% and 4.8%, respectively. SVR was seen in 61.9% of cases (55.6% in genotype 1
and 62.5% in genotype 3). CC genotype at rs12979860 and TT genotype at rs8099917
were significantly higher in responders (P = 0.013 and 0.042, respectively).
Lower baseline ALT and rapid viral response were also found to be associated with
SVR. On logistic regression analysis, CC genotype at rs12979860 emerged as the
most powerful predictor of treatment response. CONCLUSION: IL28B polymorphisms
are strong predictors of SVR in patients from the Indian subcontinent infected
with HCV genotype 3 and genotype 1.
PMID- 27514957
TI - Antimicrobial susceptibility testing of Brucella melitensis isolated from
patients with acute brucellosis in a centre of Iran.
AB - Structured to Purpose: Human brucellosis is one of the most common zoonotic
infections worldwide, which remains one of the major problems for public health.
Despite the World Health Organization's recommendation for human brucellosis
treatment, sporadic cases of relapse have been reported. The aim of this study
was to assess the susceptibility of Brucella isolates to common antibiotics that
are prescribed by the physician for the treatment of brucellosis and also to
determine the minimum inhibitory concentration 50% (MIC 50 ) and MIC 90 for these
antibiotics. MATERIALS AND METHODS: Forty-eight Brucella strains were collected
from patients with acute brucellosis. Species identification was made based on
the conventional methods. MIC of rifampin, doxycycline, ciprofloxacin,
trimethoprim- sulfamethoxazole, streptomycin, azithromycin and ceftriaxone was
determined by E-test. RESULTS: All the 48 Brucella isolates (47 blood samples and
one synovial fluid) were identified as Brucella melitensis. No antimicrobial
resistant strains were recognised. Trimethoprim-sulfamethoxazole had the lowest
MIC 50 (0.016 MUg/ml) and MIC 90 (0.064 MUg/ml), whereas MIC 50 and MIC 90 of
streptomycin and azithromycin had the highest level at 0.625, 1.5 ug/ml and 0.25,
1 ug/ml, respectively. All the isolates were susceptible to rifampin, and only
one of the isolates had a reduced sensitivity to rifampin (1 MUg/ml).
CONCLUSIONS: Although all the Brucella isolates were susceptible, antimicrobial
susceptibility test should be recommended in patients with recurrent brucellosis
or life-threatening organ involvement.
PMID- 27514958
TI - Reduced susceptibility to chlorhexidine disinfectant among New Delhi metallo-beta
lactamase-1 positive Enterobacteriaceae and other multidrug-resistant organisms:
Report from a tertiary care hospital in Karachi, Pakistan.
AB - We analysed susceptibility of multidrug-resistant organisms (MDROs) including New
Delhi metallo-beta-lactamase-1 positive Enterobacteriaceae to chlorhexidine and
compared results to their susceptible counterparts. Susceptibilities of
chlorhexidine digluconate in a standard (CHX-S) preparation and two commercial
disinfectants containing different CHX concentrations (2% w/v and 4% w/w) were
performed. MDROs had narrower range of higher CHX-S minimum inhibitory
concentrations (MICs) as compared to pan-sensitive organisms. The MIC values for
commercial disinfectants products for MDROs were many folds higher (20-600
times), than CHX-S for in vitro use. Increasing antibiotic resistance among
bacterial isolates can be an indirect marker of reduced susceptibility to
chlorhexidine in hospital setting.
PMID- 27514959
TI - Distribution of genes encoding aminoglycoside-modifying enzymes among clinical
isolates of methicillin-resistant staphylococci.
AB - The objective of this study was to determine the distribution of genes encoding
aminoglycoside-modifying enzymes (AMEs) and staphylococcal cassette chromosome
mec (SCCmec) elements among clinical isolates of methicillin-resistant
staphylococci (MRS). Antibiotic susceptibility test was done using Kirby-Bauer
disk diffusion method. The presence of SCCmec types and AME genes, namely, aac
(6')-Ie-aph (2''), aph (3')-IIIa and ant (4')-Ia was determined using two
different multiplex polymerase chain reaction. The most encountered AME genes
were aac (6')-Ie-aph (2'') (55.4%) followed by aph (3')-IIIa (32.3%) and ant (4')
Ia gene (9%). SCCmec type I (34%) was predominant in this study. In conclusion,
the aac (6')-Ie-aph (2'') was the most common AME gene and SCCmec type I was most
predominant among the MRS isolates.
PMID- 27514960
TI - The antibiotics of choice for the treatment of melioidosis in Indian set up.
AB - Therapeutic options for the treatment of melioidosis caused by Burkholderia
pseudomallei are limited due to the inherent resistance conferred by this
pathogen to various groups of antibiotics. Witnessing an increase in the number
of microbiological culture-confirmed cases of melioidosis at our settings in the
past few years, we undertook this study to estimate the minimum inhibitory
concentrations of clinical isolates of B. pseudomallei against the four commonly
employed antimicrobial agents in the patient management at our settings, namely,
ceftazidime, meropenem, trimethoprim-sulfamethoxazole and doxycycline. All
isolates were susceptible to the antibiotics tested, except for one isolate which
showed resistance to doxycycline (minimum inhibitory concentration [MIC]: 32
MUg/ml). MIC50 and 90 for all the four antibiotics were estimated. From this
study, we conclude that the clinical isolates of B. pseudomallei from the
southern part of India are well susceptible to the commonly employed
antimicrobial agents for therapy.
PMID- 27514961
TI - Reduced susceptibility of carbapenem-resistant Klebsiella pneumoniae to biocides:
An emerging threat.
AB - Dealing with carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains, which
are generally pan-drug resistant, is an uphill task for health care
professionals. Owing to limited therapeutic options and the possibility of
development of resistance to commonly used biocides in hospital settings, CR-Kp
infections pose a serious threat of emergence of a dreaded pandemic. The aim of
the study was to highlight the possibility of emergence of biocide resistance
among CR-Kp strains. A case study was conducted in a Super-specialty Hospital in
September 2015. A 65-year-old female patient post-laparotomy was admitted to the
General Intensive Care Unit of a Super-specialty Hospital. CR-Kp was isolated
from the blood and mucus trap samples of this patient. Susceptibility testing of
three commonly used biocides in our hospital, namely sodium hypochlorite (4%
available chlorine), 5% w/v povidone iodine (0.5% w/v of available iodine) and
absolute ethanol (99.9%), respectively, was carried out using K. pneumoniae ATCC
700603 as control. The test isolate showed reduced susceptibility to sodium
hypochlorite in comparison to K. pneumoniae ATCC 700603. The possibility of
emergence of biocide resistance among CR-Kp strains poses a threat of disrupting
our ongoing efforts for implementation of effective infection control measures.
PMID- 27514962
TI - Multidrug resistance mediated by co-carriage of extended-spectrum beta
lactamases, AmpC and New Delhi metallo-beta-lactamase-1 genes among carbapenem
resistant Enterobacteriaceae at five Indian medical centres.
AB - In this study, we evaluated the coexistence of extended-spectrum beta-lactamases
(ESBL), AmpC and New Delhi metallo-beta-lactamase-1 (NDM-1) genes among
carbapenem-resistant Enterobacteriaceae (CRE) recovered prospectively from
patients at multiple sites. The study included 285 CRE strains from 2782 Gram
negative Bacilli collected from multiple centres during 2007-2010, of which 87
were characterised. Standard and reference laboratory methods were used for
resistance determination. Detection of blaNDM-1 , blaAmpC , blaTEM , blaSHV and
blaCTX-M was done by polymerase chain reaction. High levels of antimicrobial
resistance observed among study isolates. Co-carriage of ESBLs, AmpC and NDM-1
was 26.3%. Nosocomial origin among the co-carriage isolates was 64.3%, with 9.2%
associated mortality.
PMID- 27514963
TI - Epidemiology and patterns of drug resistance among tuberculosis patients in
Northwestern Iran.
AB - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) has emerged as an important
global health concern and is on the rise throughout the world. OBJECTIVE: The aim
of this study was to examine the epidemiology and pattern of TB drug resistance.
METHODS: In this cross-sectional study, 180 pulmonary TB patients from two
Northwestern provinces of Iran were selected. The first and second line drug
susceptibility testing was carried out using the 1% proportion method on the
Lphiwenstein-Jensen medium. Full demographic, environmental and clinical history
was evaluated. RESULTS: Prevalence of resistance to any TB drug was 13.8%. Eight
(4.4%) patients had MDR-TB (2.4% in the province of East Azerbaijan and 9.3% in
the province of Ardabil) and one patient had extensively drug-resistant TB.
Patient resistance to both isoniazid and streptomycin was the most prevalent at a
rate of 8.3%. Patients showed the least resistance to ethambutol (2.8%). There
was a significant relationship between the previous history of TB drug treatment
and TB drug resistance. Migrants from rural to urban areas were in high-risk
groups for the occurrence of TB drug resistance. CONCLUSION: In our study,
prevalence of MDR was less than the global average. It is essential to monitor
the patients with previous history of TB treatment and migrants by rapid and
accurate techniques in terms of drug-resistance odds.
PMID- 27514964
TI - Allele-specific duplex polymerase chain reaction to differentiate Mycobacterium
abscessus subspecies and to detect highly clarithromycin-resistant isolates.
AB - On the basis of the structural differences of erm, we used a duplex polymerase
chain reaction (PCR) to differentiate Mycobacterium abscessus subsp. abscessus
and subsp. massiliense isolates and to detect the point mutations of 23S rRNA
gene that confer a high level of resistance to clarithromycin. Subsp. massiliense
strains occupying almost half of the clinical isolates can be simply identified,
and their clarithromycin susceptibility can be rapidly determined.
PMID- 27514965
TI - A cross-sectional study on aetiology of diarrhoeal disease, India.
AB - BACKGROUND: Global, regional and national estimates clearly place diarrhoeal
diseases as a major, albeit to an extant neglected public health problem. Deaths
of children aged <5 years owing to diarrhoea was estimated to be 1.87 million at
the global level (uncertainty range from 1.56 to 2.19 million), which is
approximately 19% of total child deaths. OBJECTIVES: The present report is a
cross-sectional study undertaken to estimate the role of various aetiological
agents causing diarrhoea in North Karnataka and adjoining areas of Maharashtra
and Goa. METHODS: Three hundred stool samples were collected from patients
seeking health care at KLES Dr. Prabhakar Kore Hospital and Medical Research
Centre, Belgaum; and processed for detection of various bacterial, viral and
parasitic agents. RESULTS: Bacterial pathogens attributed to 65.7% of diarrhoea
cases, followed by viral infection (22%), parasitic infection (16.3%) and
infection by Candida spp. (5.6%). The study identified Escherichia coli in
general and Enteropathogenic E. coli in particular, and Group A Rotavirus to be
the most frequently isolated pathogens among diarrhoea patients. CONCLUSION: The
data generated from the current study will help the health officials for better
interventional and treatment strategies for diarrhoeal diseases.
PMID- 27514966
TI - Noncatheter-related bacteraemia due to Chryseobacterium indologenes in an
immunocompetent patient.
AB - Chryseobacterium indologenes belongs to a group of nonfermentative Gram-negative
bacilli and is an uncommon human pathogen. It causes severe infections such as
septicaemia and ventilator-associated pneumonia in immunocompromised patients or
after prolonged hospitalisation. We report a case of a noncatheter-related
bacteraemia in a 22-year-old immunocompetent female whose blood culture showed
the growth of C. indologenes, identified by Vitek GNI system (bioMerieux,
France). The patient responded to treatment with ciprofloxacin. The pathogenicity
and virulence factors of C. indologenes remain unclear. This case indicates that
C. indologenes might cause symptomatic disease in immunocompetent persons with
otherwise no associated underlying risk factors.
PMID- 27514967
TI - Post-traumatic endophthalmitis caused by Streptococcus parauberis: First human
case report.
AB - A 12-year-old boy presented with trauma to left eye with a wooden stick. On
examination, there was full thickness corneal laceration with cataractous lens
behind the laceration. The laceration was sutured, and intravitreal injections of
vancomycin, ceftazidime and clindamycin were administered. Vitreous tap grew
Streptococcus parauberis. The isolate was sensitive to amoxicillin, erythromycin
and vancomycin, and topical vancomycin was used to treat the infection. We
present the first case of human post-traumatic infective endophthalmitis caused
by the rare agent S. parauberis.
PMID- 27514968
TI - A rare glimpse into the morbid world of necrotising fasciitis: Flesh-eating
bacteria Vibrio vulnificus.
AB - Necrotising fasciitis is one of the fatal skin and soft tissue infections. Vibrio
vulnificus is a rare cause of necrotising fasciitis; however, the disease is one
of the major manifestations of the bacteria. Here, we report one such case in a
middle-aged male patient. He presented with the signs of bilateral lower limb
cellulitis and altered sensorium. V. vulnificus was isolated from blood culture
and also from debrided tissue. Though the organism is well characterised, it is a
rare causative agent of necrotising fasciitis. This case is a re-emphasis on
active look out for this bacterium in patients presenting with necrotizsing
fasciitis.
PMID- 27514969
TI - Outbreak of enteric fever due to Salmonella Paratyphi A variety durazzo (2,12:a:
) in a hilly region of North India: A report of 43 cases.
AB - Enteric fever due to Salmonella Paratyphi A (SPA) is a global problem occurring
as outbreaks at times. An unusual SPA (2,12:a:-) variety durazzo has been
reported rarely. We report an outbreak of enteric fever due to this variety
affecting 43 individuals. The blood samples grew unusual mucoid, lactose non
fermenting colonies with atypical biochemical reactions in sugar fermentation and
amino acid decarboxylation. Isolates had sensitivity to ceftriaxone,
chloramphenical, cotrimoxazole, intermediate susceptibility to ciprofloxacin and
resistance to ampicillin and nalidixic acid. Identification was confirmed as SPA
(2,12:a:-) at the National Salmonella Centre.
PMID- 27514970
TI - Leptospirosis in sub-Himalayan region: A neglected entity.
PMID- 27514971
TI - Awareness and practices regarding biomedical waste management among health-care
workers in a tertiary care hospital in Delhi: Comment.
PMID- 27514972
TI - Predatory publisher and impact factor: The murky landscape of scholastic
publication.
PMID- 27514973
TI - An unusual case of blackwater fever.
PMID- 27514974
TI - Spontaneous septic arthritis due to Burkholderia cepacia in a 3-month-old pre
term infant.
PMID- 27514975
TI - Aeromonas : An unusual cause of lower gastrointestinal bleed.
PMID- 27514976
TI - Azithromycin susceptibility among clinical isolates of Salmonella: Interfacing
guidelines with routine practices.
PMID- 27514977
TI - Daptomycin: A viable therapeutic option for vancomycin-resistant enterococcal
urinary-tract infections in Indian medical settings?
PMID- 27514978
TI - Occurrence of aac(6')-Ib variants among Enterobacteriaceae: Is aac(6')-Ib-cr the
most predominant variant?
PMID- 27514979
TI - Analysis of samples processed in automated blood culture system with blood
culture samples processed by conventional manual method.
PMID- 27514980
TI - Granulicatella adiacens : An unusual isolate from urethral discharge.
PMID- 27514981
TI - Phthirus pubis in the eye.
PMID- 27514982
TI - In vitro demonstration of potential virulence determinants among clinical
isolates of various Candida species and its clinical implication in a Teaching
Hospital in Eastern India.
PMID- 27514983
TI - Presence of Epstein-Barr virus in gastric adenocarcinoma in Indian patients.
PMID- 27514984
TI - Awareness about needlestick harms and health seeking behaviour among the Safai
Karamcharis at Dr. Rajendra Prasad Government Medical College Kangra at Tanda
(Himachal Pradesh).
PMID- 27514985
TI - The neuronal mechanisms underlying improvement of impulsivity in ADHD by
theta/beta neurofeedback.
AB - Neurofeedback is increasingly recognized as an intervention to treat core
symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large
number of studies having been carried out to evaluate its effectiveness, it is
widely elusive what neuronal mechanisms related to the core symptoms of ADHD are
modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of
theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in
a pre-post design. We used neurophysiological measures combining high-density EEG
recording with source localization analyses using sLORETA. Compared to the
waiting list ADHD control group, impulsive behaviour measured was reduced after
neurofeedback treatment. The effects of neurofeedback were very specific for
situations requiring inhibitory control over responses. The neurophysiological
data shows that processes of perceptual gating, attentional selection and
resource allocation processes were not affected by neurofeedback. Rather,
neurofeedback effects seem to be based on the modulation of response inhibition
processes in medial frontal cortices. The study shows that specific neuronal
mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in
ADHD. The applied neurofeedback protocol could be particularly suitable to
address inhibitory control. The study validates assumed functional
neuroanatomical target regions of an established neurofeedback protocol on a
neurophysiological level.
PMID- 27514987
TI - Full data acquisition in Kelvin Probe Force Microscopy: Mapping dynamic electric
phenomena in real space.
AB - Kelvin probe force microscopy (KPFM) has provided deep insights into the local
electronic, ionic and electrochemical functionalities in a broad range of
materials and devices. In classical KPFM, which utilizes heterodyne detection and
closed loop bias feedback, the cantilever response is down-sampled to a single
measurement of the contact potential difference (CPD) per pixel. This level of
detail, however, is insufficient for materials and devices involving bias and
time dependent electrochemical events; or at solid-liquid interfaces, where non
linear or lossy dielectrics are present. Here, we demonstrate direct recovery of
the bias dependence of the electrostatic force at high temporal resolution using
General acquisition Mode (G-Mode) KPFM. G-Mode KPFM utilizes high speed
detection, compression, and storage of the raw cantilever deflection signal in
its entirety at high sampling rates. We show how G-Mode KPFM can be used to
capture nanoscale CPD and capacitance information with a temporal resolution much
faster than the cantilever bandwidth, determined by the modulation frequency of
the AC voltage. In this way, G-Mode KPFM offers a new paradigm to study dynamic
electric phenomena in electroactive interfaces as well as a promising route to
extend KPFM to the solid-liquid interface.
PMID- 27514988
TI - Comparison of Phytochemical Composition and Biological Activities of Rubus
ulmifolius Extracts Originating from Four Regions of Tunisia.
AB - In the current study, the phenolic composition, antioxidant and antimicrobial
activities of extracts from Rubus ulmifolius Schott leaves harvested in four
localities (Sejnen, Tabarka, Faija and Ain drahem) in Tunisia were investigated
for the first time. Great differences were found for the chemical composition,
total phenol contents and biological activities among the evaluated extracts.
HPLC analysis of methanolic extracts showed that the dominant compounds were
kaempferol 3-O-rutinoside and naringenine. In addition, significant correlations
were observed between antioxidant activities and phenolic contents. In fact,
leaves collected from Sejnen presented higher total phenol content (53.32 mg
GAE/g DW) and antioxidant activities (IC50 = 39.40 mg/l) than the others samples.
All extracts showed significant antimicrobial activity against six used bacteria
with the inhibition zones diameters and minimal inhibitory concentration values
were in the range of 8 - 16 mm and 6.25 - 25 mg/ml, respectively. The highest
antimicrobial activities were recorded in Sejnen extract against Gram-positive
bacteria.
PMID- 27514986
TI - Global transcriptional analysis suggests Lasiodiplodia theobromae pathogenicity
factors involved in modulation of grapevine defensive response.
AB - BACKGROUND: Lasiodiplodia theobromae is a fungus of the Botryosphaeriaceae that
causes grapevine vascular disease, especially in regions with hot climates. Fungi
in this group often remain latent within their host and become virulent under
abiotic stress. Transcriptional regulation analysis of L. theobromae exposed to
heat stress (HS) was first carried out in vitro in the presence of grapevine wood
(GW) to identify potential pathogenicity genes that were later evaluated for in
planta expression. RESULTS: A total of 19,860 de novo assembled transcripts were
obtained, forty-nine per cent of which showed homology to the Botryosphaeriaceae
fungi, Neofusicoccum parvum or Macrophomina phaseolina. Three hundred ninety-nine
have homology with genes involved in pathogenic processes and several belonged to
expanded gene families in others fungal grapevine vascular pathogens. Gene
expression analysis showed changes in fungal metabolism of phenolic compounds;
where genes encoding for enzymes, with the ability to degrade salicylic acid (SA)
and plant phenylpropanoid precursors, were up-regulated during in vitro HS
response, in the presence of GW. These results suggest that the fungal L-tyrosine
catabolism pathway could help the fungus to remove phenylpropanoid precursors
thereby evading the host defense response. The in planta up-regulation of
salicylate hydroxylase, intradiol ring cleavage dioxygenase and
fumarylacetoacetase encoding genes, further supported this hypothesis. Those
genes were even more up-regulated in HS-stressed plants, suggesting that fungus
takes advantage of the increased phenylpropanoid precursors produced under
stress. Pectate lyase was up-regulated while a putative amylase was down
regulated in planta, this could be associated with an intercellular growth
strategy during the first stages of colonization. CONCLUSIONS: L. theobromae
transcriptome was established and validated. Its usefulness was demonstrated
through the identification of genes expressed during the infection process. Our
results support the hypothesis that heat stress facilitates fungal colonization,
because of the fungus ability to use the phenylpropanoid precursors and SA, both
compounds known to control host defense.
PMID- 27514989
TI - Impact of Precursor Compositions on the Structural and Photovoltaic Properties of
Spray-Deposited Cu2 ZnSnS4 Thin Films.
AB - Pure sulfide Cu2 ZnSnS4 thin films were fabricated on Mo-coated glass substrates
by facile spray deposition of aqueous precursor solutions containing Cu(NO3 )2 ,
Zn(NO3 )2 , Sn(CH3 SO3 )2 , and thiourea followed by annealing at 600 degrees C.
When a precursor solution containing a stoichiometric composition of Cu, Zn, and
Sn was used, the resulting Cu2 ZnSnS4 thin film contained a Cu2-x S impurity
phase owing to the evaporation of Sn components during the annealing process. The
Cu2-x S impurity in the Cu2 ZnSnS4 thin film was removed by reducing the
concentration of Cu in the precursor solution. This resulted in an improvement of
the structural features (i.e., grain sizes and compactness) as well as the
electric properties such as acceptor densities, the nature of the acceptor
defects, and carrier lifetimes. A solar cell based on the Cu2 ZnSnS4 film with an
empirically optimal composition showed conversion efficiency of 8.1 %. The value
achieved was one of the best efficiencies of Cu2 ZnSnS4 -based cells derived from
a non-vacuum process.
PMID- 27514991
TI - Combination of Metabolomics with Cellular Assays Reveals New Biomarkers and
Mechanistic Insights on Xenoestrogenic Exposures in MCF-7 Cells.
AB - The disruptive potential of xenoestrogens like bisphenol A (BPA) lies in their
17beta-estradiol (E2)-like binding to estrogen receptors (ERs) followed by
concomitant modulation of ER target gene expression. Unsurprisingly, most
endocrine testing systems focus on the quantification of canonical transcripts or
ER-sensitive reporters. However, only little information is available about the
corresponding metabolomic changes in vitro. This knowledge gap becomes
particularly relevant in the context of potential mixture effects, for example,
as a consequence of coexposure to potentially estrogenically active pollutants
(e.g., Cd2+). Such effects are often difficult to dissect with molecular tools,
especially with regard to potential physiological relevance. Metabolomic
biomarkers are well-suited to address this latter aspect as they provide a
comprehensive readout of whole-cell physiology. Applying a targeted metabolomics
approach (FIA-MS/MS), this study looked for biomarkers indicative of
xenoestrogenic exposure in MCF-7 cells. Cells were treated with E2 and BPA in the
presence or absence of Cd2+. Statistical analysis revealed a total of 11 amino
acids and phospholipids to be related to the compound's estrogenic potency. Co
exposure to Cd2+ modulated the estrogenic profile. However, the corresponding
changes were found to be moderate with cellular assays such as the E-screen
failing to record any Cd2+-specific estrogenic effects. Overall, metabolomics
analysis identified proline as the most prominent estrogenic biomarker. Its
increase could clearly be related to estrogenic exposure and concomitant ERalpha
mediated induction of proliferation. Involvement of the latter was confirmed by
siRNA-mediated knockdown studies as well as by receptor inhibition. Further, the
underlying signaling was also found to involve the oncoprotein MYC. Taken
together, this study provides insights into the underlying mechanisms of
xenoestrogenic effects and exemplify the strength of the complementary use of
metabolomics and cellular and molecular assays.
PMID- 27514990
TI - Neuroprotective effects of apigenin against inflammation, neuronal excitability
and apoptosis in an induced pluripotent stem cell model of Alzheimer's disease.
AB - Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases,
yet current therapeutic treatments are inadequate due to a complex disease
pathogenesis. The plant polyphenol apigenin has been shown to have anti
inflammatory and neuroprotective properties in a number of cell and animal
models; however a comprehensive assessment has not been performed in a human
model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model
of familial and sporadic AD, in addition to healthy controls, to assess the
neuroprotective activity of apigenin. The iPSC-derived AD neurons demonstrated a
hyper-excitable calcium signalling phenotype, elevated levels of nitrite,
increased cytotoxicity and apoptosis, reduced neurite length and increased
susceptibility to inflammatory stress challenge from activated murine microglia,
in comparison to control neurons. We identified that apigenin has potent anti
inflammatory properties with the ability to protect neurites and cell viability
by promoting a global down-regulation of cytokine and nitric oxide (NO) release
in inflammatory cells. In addition, we show that apigenin is able to protect iPSC
derived AD neurons via multiple means by reducing the frequency of spontaneous
Ca(2+) signals and significantly reducing caspase-3/7 mediated apoptosis. These
data demonstrate the broad neuroprotective action of apigenin against AD
pathogenesis in a human disease model.
PMID- 27514992
TI - Fast live-cell conventional fluorophore nanoscopy with ImageJ through super
resolution radial fluctuations.
AB - Despite significant progress, high-speed live-cell super-resolution studies
remain limited to specialized optical setups, generally requiring intense
phototoxic illumination. Here, we describe a new analytical approach, super
resolution radial fluctuations (SRRF), provided as a fast graphics processing
unit-enabled ImageJ plugin. In the most challenging data sets for super
resolution, such as those obtained in low-illumination live-cell imaging with
GFP, we show that SRRF is generally capable of achieving resolutions better than
150 nm. Meanwhile, for data sets similar to those obtained in PALM or STORM
imaging, SRRF achieves resolutions approaching those of standard single-molecule
localization analysis. The broad applicability of SRRF and its performance at low
signal-to-noise ratios allows super-resolution using modern widefield, confocal
or TIRF microscopes with illumination orders of magnitude lower than methods such
as PALM, STORM or STED. We demonstrate this by super-resolution live-cell imaging
over timescales ranging from minutes to hours.
PMID- 27514993
TI - Efficient sample preparation method based on solvent-assisted dispersive solid
phase extraction for the trace detection of butachlor in urine and waste water
samples.
AB - In this work, an efficient sample preparation method termed solvent-assisted
dispersive solid-phase extraction was applied. The used sample preparation method
was based on the dispersion of the sorbent (benzophenone) into the aqueous sample
to maximize the interaction surface. In this approach, the dispersion of the
sorbent at a very low milligram level was achieved by inserting a solution of the
sorbent and disperser solvent into the aqueous sample. The cloudy solution
created from the dispersion of the sorbent in the bulk aqueous sample. After pre
concentration of the butachlor, the cloudy solution was centrifuged and butachlor
in the sediment phase dissolved in ethanol and determined by gas chromatography
with flame ionization detection. Under the optimized conditions (solution pH =
7.0, sorbent: benzophenone, 2%, disperser solvent: ethanol, 500 MUL, centrifuged
at 4000 rpm for 3 min), the method detection limit for butachlor was 2, 3 and 3
MUg/L for distilled water, waste water, and urine sample, respectively.
Furthermore, the preconcentration factor was 198.8, 175.0, and 174.2 in distilled
water, waste water, and urine sample, respectively. Solvent-assisted dispersive
solid-phase extraction was successfully used for the trace monitoring of
butachlor in urine and waste water samples.
PMID- 27514994
TI - Robinson and madison have published no data on whether polyethylene glycol fusion
repair prevents reinnervation accuracy in rat peripheral nerve.
PMID- 27514995
TI - Antioxidative therapy in an ex vivo human cartilage trauma-model: attenuation of
trauma-induced cell loss and ECM-destructive enzymes by N-acetyl cysteine.
AB - OBJECTIVE: Mechanical trauma of articular cartilage results in cell loss and
cytokine-driven inflammatory response. Subsequent accumulation of reactive oxygen
(ROS) and nitrogen (RNS) species enhances the enzymatic degradation of the
extracellular matrix (ECM). This study aims on the therapeutic potential of N
acetyl cysteine (NAC) in a human ex vivo cartilage trauma-model, focusing on cell
and chondroprotective features. DESIGN: Human full-thickness cartilage explants
were subjected to a defined impact trauma (0.59 J) and treated with NAC.
Efficiency of NAC administration was evaluated by following outcome parameters:
cell viability, apoptosis rate, anabolic/catabolic gene expression, secretion and
activity of matrix metalloproteinases (MMPs) and proteoglycan (PG) release.
RESULTS: Continuous NAC administration increased cell viability and reduced the
apoptosis rate after trauma. It also suppressed trauma-induced gene expression of
ECM-destructive enzymes, such as ADAMTS-4, MMP-1, -2, -3 and -13 in a dosage- and
time-depending manner. Subsequent suppression of MMP-2 and MMP-13 secretion
reflected these findings on protein level. Moreover, NAC inhibited proteolytic
activity of MMPs and reduced PG release. CONCLUSION: In the context of this ex
vivo study, we showed not only remarkable cell- and chondroprotective features,
but also revealed new encouraging findings concerning the therapeutically
effective concentration and treatment-time regimen of NAC. Its defense against
chondrocyte apoptosis and catabolic enzyme secretion recommends NAC as a
multifunctional add-on reagent for pharmaceutical intervention after cartilage
injury. Taken together, our data increase the knowledge on the therapeutic
potential of NAC after cartilage trauma and presents a basis for future in vivo
studies.
PMID- 27514998
TI - Clinical and Molecular Aspects of MBD5-Associated Neurodevelopmental Disorder
(MAND).
PMID- 27514996
TI - Synovial macrophages promote TGF-beta signaling and protect against influx of
S100A8/S100A9-producing cells after intra-articular injections of oxidized low
density lipoproteins.
AB - OBJECTIVE: Low-density lipoproteins (LDL) in inflamed synovium is oxidized and
taken-up by synoviocytes. In this study, we investigate whether direct injection
of oxidized LDL (oxLDL) into a normal murine knee joint induces joint pathology
and whether synovial macrophages are involved in that process. DESIGN: Synovium
was obtained from end-stage osteoarthritis (OA) patients in order to analyze LDL
uptake. Murine knee joints were injected five consecutive days with oxLDL, LDL,
or vehicle (phosphate buffered saline (PBS)). This procedure was repeated in mice
depleted of synovial macrophages by intra-articular injection of clodronate
liposomes 7 days prior to the consecutive injections. Joint pathology was
investigated by immunohistochemistry, flow cytometry (FCM) and synovial RNA
expression and protein production. RESULTS: Synovial tissue of OA patients showed
extensive accumulation of apolipoprotein B. Multiple injections of oxLDL in
murine knee joints significantly increased TGF-beta activity in synovial wash
outs, but did not induce catabolic or inflammatory processes. In contrast,
repeated injections of oxLDL in macrophage-depleted knee joints led to increased
synovial thickening in combination with significantly upregulated protein and RNA
levels of CCL2 and CCL3. FCM-analyses revealed increased presence of monocytes
and neutrophils in the synovium, which was confirmed by immunohistochemistry.
Also protein levels of S100A8/A9 were significantly increased in synovial wash
outs of oxLDL-injected joints, as was expression of aggrecanase-induced neo
epitopes. Interestingly, no raise in TGF-beta concentrations was measured in
macrophage-depleted joints. CONCLUSIONS: OxLDL can affect joint pathology, since
synovial macrophages promote anabolic processes after oxLDL injections. In
absence of synovial macrophages, however, oxLDL induces production of pro
inflammatory mediators and aggrecanase activity combined with increased influx of
monocytes and neutrophils.
PMID- 27514999
TI - Long-term culture of human odontoma-derived cells with a Rho kinase inhibitor.
AB - Because of cellular senescence/apoptosis, no effective culture systems are
available to maintain replication of cells from odontogenic tumors especially for
odontoma, and, thus, the ability to isolate human odontoma-derived cells (hODCs)
for functional studies is needed. The current study was undertaken to develop an
approach to isolate hODCs and fully characterize the cells in vitro. The hODCs
were cultured successfully with a Rho-associated protein kinase inhibitor (Y
27632) for an extended period with stabilized lengths of the telomeres to sustain
a similar phenotype/property as the primary tumoral cells. While the hODCs showed
stable long-term expansion with expression of major dental epithelial markers
including dentin sialophosphoprotein (DSPP) even in the three-dimensional
microenvironment, they lack the specific markers for the characteristics of stem
cells. Moreover, cells from dental pulp showed significant up-regulation of DSPP
when co-cultured with the hODCs, while control fibroblasts with the hODCs did
not. Taken together, we propose that the hODCs can be isolated and expanded over
the long term with Y-27632 to investigate not only the development of the hODCs
but also other types of benign human tumors.
PMID- 27515000
TI - Mitochondrial reactive oxygen species mediate the lipopolysaccharide-induced pro
inflammatory response in human gingival fibroblasts.
AB - Although periodontal diseases are initiated by bacteria that colonize the tooth
surface and gingival sulcus, the host response is believed to play an essential
role in the breakdown of connective tissue and bone. Mitochondrial reactive
oxygen species (mtROS) have been proposed to regulate the activation of the
inflammatory response by the innate immune system. However, the role of mtROS in
modulating the response of human gingival fibroblasts (HGFs) to immune
stimulation by lipopolysaccharides (LPS) has yet to be fully elucidated. Here, we
showed that LPS from Porphyromonas gingivalis stimulated HGFs to increase mtROS
production, which could be inhibited by treatment with a mitochondrial-targeted
exogenous antioxidant (mito-TEMPO) or transfection with manganese superoxide
dismutase (MnSOD). A time-course study revealed that an increase in the
concentration of mtROS preceded the expression of inflammatory cytokines in HGFs.
Mito-TEMPO treatment or MnSOD transfection also significantly prevented the LPS
induced increase of interleukin (IL)-1beta, IL-6, and tumor necrosis factor
alpha. Furthermore, suppressing LPS-induced mtROS generation inhibited the
activation of p38, c-Jun N-terminal kinase, and inhibitor of nuclear factor
kappaB kinase, as well as the nuclear localization of nuclear factor-kappaB.
These results demonstrate that mtROS generation is a key signaling event in the
LPS-induced pro-inflammatory response of HGFs.
PMID- 27515001
TI - Time-lapse phenotyping of invasive glioma cells ex vivo reveals subtype-specific
movement patterns guided by tumor core signaling.
AB - The biology of glioblastoma invasion and its mechanisms are poorly understood. We
demonstrate using time-lapse microscopy that grafting of glioblastoma (GBM)
tumorspheres into rodent brain slices results in experimental ex vivo tumors with
invasive properties that recapitulate the invasion observed after orthotopic
transplantation into the rodent brain. The migratory movements and mitotic
patterns were clearly modified by signals extrinsic to the invading cells. The
cells migrated away from the tumorspheres, and removal of the spheres reduced the
directed invasive movement. The cell cultures contained different populations of
invasive cells that had distinct morphology and invasive behavior patterns.
Grafts of the most invasive GBM culture contained 91+/-8% cells with an invasive
phenotype, characterized by small soma with a distinct leading process.
Conversely, the majority of cells in less invasive GBM grafts were phenotypically
heterogeneous: only 6.3+/-4.1% of the cells had the invasive phenotype. Grafts of
highly and moderately invasive cultures had different proportions of cells that
advanced into the brain slice parenchyma during the observation period: 89.2+/
2.2% and 23.1+/-6.8%, respectively. In grafts with moderately invasive
properties, most of the cells (76.8+/-6.8%) invading the surrounding brain tissue
returned to the tumor bulk or stopped centrifugal migration. Our data suggest
that the invasion of individual GBM tumors can be conditioned by the prevalence
of a cell fraction with particular invasive morphology and by signaling between
the tumor core and invasive cells. These findings can be important for the
development of new therapeutic strategies that target the invasive GBM cells.
PMID- 27515003
TI - Systemic over-release of interleukin-17 in acute kidney injury after septic
shock: Clinical and experimental evidence.
AB - In order to investigate the role of T-helper 17 (Th17) cell activation in acute
kidney injury (AKI) after septic shock, a two-stage approach was used. Firstly,
peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were isolated the
first 24h after septic shock from 26 patients with AKI and 18 patients with
chronic renal disease (CRD) without AKI and stimulated for the release of tumour
necrosis factor-alpha (TNFalpha), interleukin (IL)-10, IL-17, IL-22 and
interferon-gamma (IFNgamma). Results were compared with 15 healthy volunteers and
13 patients with uncomplicated sepsis. Secondly, a murine model of multiple organ
dysfunction (MODS) complicated with AKI and bacterial gut translocation was
studied, and IL-10, IL-17, IL-22 and IFNgamma were measured in kidney
homogenates. IL-17 was the only cytokine produced at greater quantities from
PBMCs and CD4-lymphocytes of patients with septic shock and AKI than comparators.
When PBMCs of patients with septic shock and AKI were ex-vivo stimulated,
intracellular staining for IL-17 was greater in CD3(+)/CD4(+)/CD196(+) cells
compared to patients with septic shock and CRD. IL-17 was released at greater
amounts from PBMCs of non-survivors by septic shock and AKI but not of septic
shock and CRD. In the murine model of MODS, a gradual decrease of IL-17, but not
of IL-10, IL-22 and IFNgamma, of kidney homogenates was found indicating over
consumption. These results suggest that AKI after septic shock is driven through
IL-17 release by Th17 cells; this is gradually consumed in the kidney.
PMID- 27515004
TI - Effect of genotyped cows in the reference population on the genomic evaluation of
Holstein cattle.
AB - This study evaluated the dependence of reliability and prediction bias on the
prediction method, the contribution of including animals (bulls or cows), and the
genetic relatedness, when including genotyped cows in the progeny-tested bull
reference population. We performed genomic evaluation using a Japanese Holstein
population, and assessed the accuracy of genomic enhanced breeding value (GEBV)
for three production traits and 13 linear conformation traits. A total of 4564
animals for production traits and 4172 animals for conformation traits were
genotyped using Illumina BovineSNP50 array. Single- and multi-step methods were
compared for predicting GEBV in genotyped bull-only and genotyped bull-cow
reference populations. No large differences in realized reliability and
regression coefficient were found between the two reference populations; however,
a slight difference was found between the two methods for production traits. The
accuracy of GEBV determined by single-step method increased slightly when
genotyped cows were included in the bull reference population, but decreased
slightly by multi-step method. A validation study was used to evaluate the
accuracy of GEBV when 800 additional genotyped bulls (POPbull) or cows (POPcow)
were included in the base reference population composed of 2000 genotyped bulls.
The realized reliabilities of POPbull were higher than those of POPcow for all
traits. For the gain of realized reliability over the base reference population,
the average ratios of POPbull gain to POPcow gain for production traits and
conformation traits were 2.6 and 7.2, respectively, and the ratios depended on
heritabilities of the traits. For regression coefficient, no large differences
were found between the results for POPbull and POPcow. Another validation study
was performed to investigate the effect of genetic relatedness between cows and
bulls in the reference and test populations. The effect of genetic relationship
among bulls in the reference population was also assessed. The results showed
that it is important to account for relatedness among bulls in the reference
population. Our studies indicate that the prediction method, the contribution
ratio of including animals, and genetic relatedness could affect the prediction
accuracy in genomic evaluation of Holstein cattle, when including genotyped cows
in the reference population.
PMID- 27515002
TI - Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast
cancer cells.
AB - Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating
patients with estrogen receptor alpha (ERalpha)+ breast cancer. We reported that
ERalpha increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear
encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1
knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is
altered in endocrine resistant breast cancer cells is unknown. We measured NRF
1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and
its target mitochondrial transcription factor A (TFAM) were higher in TAM
resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular
flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen
consumption rate (OCR), but lower mitochondrial reserve capacity which was
correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2
cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and
LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher
aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses
to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells
compared to MCF-7 cells. These results suggest the acquisition of altered
metabolic phenotypes in response to long term antiestrogen treatment may increase
vulnerability to metabolic stress.
PMID- 27515005
TI - Overexpression of myosin VI regulates gastric cancer cell progression.
AB - Myosin VI (MYO6) is a unique member of the myosin superfamily. Although it has
been reported to participate in human cancer progression, the role of MYO6 in
gastric cancer remains unclear. In this study, we found the expression of MYO6
gene was higher in gastric cancer tissues than in the normal tissues by Oncomine
database mining and affects patient overall survival using the Kaplan-Meier
plotter online analysis. Additionally, the expression levels of MYO6 were widely
expressed in gastric cancer cells by quantitative real-time Polymerase Chain
Reaction (qRT-PCR) and western blot assay. Then knockdown of MYO6 significantly
suppressed the proliferation and colony formation abilities of AGS and MGC80-3
cells. Moreover, cell cycle analysis showed that inhibition of MYO6 induced cell
cycle arrested in G0/G1 phase in AGS and MGC80-3 cells. Further analysis showed
knockdown of MYO6 downregulated cell-cycle activators cyclin A and cyclin D1 and
upregulated cell-cycle inhibitor p21, as determined by qRT-PCR and western blot
analysis in MGC80-3 cells. Meanwhile, MYO6 inhibition significantly induced
apoptosis in AGS and MGC80-3 cells. Also, knockdown of MYO6 increased the
expression of apoptosis-related proteins Bax and cleaved Caspase-3, and decreased
Bcl-2 expression by western blot analysis in MGC80-3 cells. In addition, MYO6
knockdown also inhibited cell migration ability in MGC80-3 cells. Taken together,
our study indicates that MYO6 may play an important role in gastric cancer
tumorigenesis and may serve as a potential therapeutic target in human gastric
cancer.
PMID- 27515006
TI - MicroRNA and target gene expression based clustering of oral cancer, precancer
and normal tissues.
AB - PURPOSE: Development of oral cancer is usually preceded by precancerous lesion.
Despite histopathological diagnosis, development of disease specific biomarkers
continues to be a promising field of study. Expression of miRNAs and their target
genes was studied in oral cancer and two types of precancer lesions to look for
disease specific gene expression patterns. METHODS: Expression of miR-26a, miR
29a, miR-34b and miR-423 and their 11 target genes were determined in 20 oral
leukoplakia, 20 lichen planus and 20 cancer tissues with respect to 20 normal
tissues using qPCR assay. Expression data were, then, used for cluster analysis
of normal as well as disease tissues. RESULTS: Expression of miR-26a and miR-29a
was significantly down regulated in leukoplakia and cancer tissues but up
regulated in lichen planus tissues. Expression of target genes such as, ADAMTS7,
ATP1B1, COL4A2, CPEB3, CDK6, DNMT3a and PI3KR1 was significantly down regulated
in at least two of three disease types with respect to normal tissues. Negative
correlations between expression levels of miRNAs and their targets were observed
in normal tissues but not in disease tissues implying altered miRNA-target
interaction in disease state. Specific expression profile of miRNAs and target
genes formed separate clusters of normal, lichen planus and cancer tissues.
CONCLUSION: Our results suggest that alterations in expression of selected miRNAs
and target genes may play important roles in development of precancer to cancer.
Expression profiles of miRNA and target genes may be useful to differentiate
cancer and lichen planus from normal tissues, thereby bolstering their role in
diagnostics.
PMID- 27515007
TI - Efficient Enzymatic Preparation of (13) N-Labelled Amino Acids: Towards
Multipurpose Synthetic Systems.
AB - Nitrogen-13 can be efficiently produced in biomedical cyclotrons in different
chemical forms, and its stable isotopes are present in the majority of
biologically active molecules. Hence, it may constitute a convenient alternative
to Fluorine-18 and Carbon-11 for the preparation of positron-emitter-labelled
radiotracers; however, its short half-life demands for the development of simple,
fast, and efficient synthetic processes. Herein, we report the one-pot, enzymatic
and non-carrier-added synthesis of the (13) N-labelled amino acids l-[(13)
N]alanine, [(13) N]glycine, and l-[(13) N]serine by using l-alanine dehydrogenase
from Bacillus subtilis, an enzyme that catalyses the reductive amination of alpha
keto acids by using nicotinamide adenine dinucleotide (NADH) as the redox
cofactor and ammonia as the amine source. The integration of both l-alanine
dehydrogenase and formate dehydrogenase from Candida boidinii in the same
reaction vessel to facilitate the in situ regeneration of NADH during the
radiochemical synthesis of the amino acids allowed a 50-fold decrease in the
concentration of the cofactor without compromising reaction yields. After
optimization of the experimental conditions, radiochemical yields were sufficient
to carry out in vivo imaging studies in small rodents.
PMID- 27515008
TI - Reflections on scientific collaboration between basic researchers and clinicians.
AB - Early career researchers face uncertainties with respect to their job prospects
due to dwindling job markets, decreased availability of funding and undefined
career paths. As basic researchers and clinicians tend to have different
approaches to scientific problems, there are many advantages from successful
collaborations between them. Here, we discuss how collaborations between basic
and clinical scientists should be promoted early in their careers. To achieve
this, researchers, both basic and clinical, must be proactive during their
training and early stages of their careers. Mentors can further augment
collaborative links in many ways. We suggest that universities and institutions
might reassess their involvement in promoting collaborations between basic and
clinical researchers. We hope that this paper will serve as a reminder of the
importance of such collaborations, and provide the opportunity for all members of
the scientific community to reflect on and ameliorate their own contributions.
PMID- 27515009
TI - Web-Based Virtual Microscopy of Digitized Blood Slides for Malaria Diagnosis: An
Effective Tool for Skills Assessment in Different Countries and Environments.
AB - BACKGROUND: Morphological examination of blood films remains the reference
standard for malaria diagnosis. Supporting the skills required to make an
accurate morphological diagnosis is therefore essential. However, providing
support across different countries and environments is a substantial challenge.
OBJECTIVE: This paper reports a scheme supplying digital slides of malaria
infected blood within an Internet-based virtual microscope environment to users
with different access to training and computing facilities. The feasibility of
the approach was established, allowing users to test, record, and compare their
own performance with that of other users. METHODS: From Giemsa stained thick and
thin blood films, 56 large high-resolution digital slides were prepared, using
high-quality image capture and 63x oil-immersion objective lens. The individual
images were combined using the photomerge function of Adobe Photoshop and then
adjusted to ensure resolution and reproduction of essential diagnostic features.
Web delivery employed the Digital Slidebox platform allowing digital microscope
viewing facilities and image annotation with data gathering from participants.
RESULTS: Engagement was high with images viewed by 38 participants in five
countries in a range of environments and a mean completion rate of 42/56 cases.
The rate of parasite detection was 78% and accuracy of species identification was
53%, which was comparable with results of similar studies using glass slides.
Data collection allowed users to compare performance with other users over time
or for each individual case. CONCLUSIONS: Overall, these results demonstrate that
users worldwide can effectively engage with the system in a range of
environments, with the potential to enhance personal performance through
education, external quality assessment, and personal professional development,
especially in regions where educational resources are difficult to access.
PMID- 27515010
TI - Optimization of fertilization characteristics of urine by addition of
Nitrosomonas europaea bio-seed.
AB - BACKGROUND: Because of the high concentration of nutrients in human urine, its
utilization as an organic fertilizer has been notable throughout history.
However, the nitrogen compounds in urine are not stable. Therefore, to convert
urine into a suitable fertilizer, it is important to stabilize and adjust
unstable nitrogen compounds such as ammonia. Because nitrification can influence
the nitrogen profile, the use of nitrifying microorganisms can be useful for
stabilizing the nitrogen profile of urine. This study investigated the changes in
nitrogen compounds in pure urine and examined the effect of adding Nitrosomonas
europaea bio-seed solution on these changes. RESULTS: It was found that the
addition of bio-seed could reduce nitrogen loss as well as the time required to
stabilize the nitrogen profile. Furthermore, the optimum concentration of bio
seed (6 * 10(5) N. europaea cells L(-1) ) that not only leads to the least
nutrient loss but also results in an adequate nitrate/ammonium ratio and
regulates the amount of nitrate produced, thereby preventing over-fertilization,
was determined. CONCLUSION: At this concentration, no dilution or dewatering is
required, thus minimizing water and energy consumption. Usage of the optimum of
concentration of bio-seed will also eliminate the need for inorganic chemical
additives. (c) 2016 Society of Chemical Industry.
PMID- 27515011
TI - Clinical utility of non-invasive prenatal testing in pregnancies with ultrasound
anomalies.
AB - OBJECTIVE: To evaluate the application of non-invasive prenatal testing (NIPT) as
an alternative to invasive diagnostic prenatal testing in pregnancies with
abnormal ultrasound findings. METHODS: This was a retrospective analysis of 251
singleton and multiple pregnancies at high risk for fetal chromosomal abnormality
based on findings at sonographic examination, in which NIPT was performed as a
first-tier genetic test. NIPT was performed by massively parallel sequencing of
cell-free DNA in maternal plasma, allowing genome-wide detection of whole
chromosome, as well as partial, autosomal aneuploidy. Sex chromosomes were not
analyzed, according to the current protocol in Dutch laboratories. RESULTS: NIPT
was performed at a median gestational age of 20 weeks, indicated by the presence
of multiple congenital anomalies (n = 13), isolated structural anomalies (n =
57), increased nuchal translucency >= 3.5 mm (n = 58), soft markers (n = 73),
growth restriction (n = 40) and other anomalies (n = 10). NIPT results were
normal in 224 (89.2%) pregnancies, inconclusive in one (0.4%) and abnormal in 26
(10.4%). Most genetic aberrations detected by NIPT were common whole-chromosome
aneuploidies: trisomy 21 (n = 13), trisomy 18 (n = 6) and trisomy 13 (n = 3).
Four further NIPT results were abnormal; one was suspected of being confined
placental mosaicism and one was of maternal origin. In those with normal NIPT
results, sonographic follow-up or examination of the newborn indicated the need
for diagnostic genetic testing in 33/224 (14.7%) pregnancies. Clinically relevant
genetic aberrations were revealed in 7/224 (3.1%) cases, two of which were whole
chromosome aneuploidies: trisomy 13 and monosomy X. As sex chromosomal
aberrations are not included in NIPT analysis, the latter cannot be considered a
false-negative result. Other discordant findings were subchromosomal aberrations
(< 20 megabases, n = 2) and monogenic aberrations (n = 3). CONCLUSIONS: NIPT
should not be recommended for genetic evaluation of the etiology of ultrasound
anomalies, as both resolution and sensitivity, or negative predictive value, are
inferior to those of conventional karyotyping and microarray analysis.
Nonetheless, some pregnant women consider NIPT to be an acceptable alternative to
invasive diagnostic testing. (c) 2016 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- 27515012
TI - The extent and nature of television food advertising to children in Xi'an, China.
AB - BACKGROUND: To explore the extent and nature of television food advertising
especially unhealthy food advertising to primary school children in Xi'an, China.
METHODS: Television data were recorded for 2 weekdays and 2 weekend days between
6:00 and 22:00 during May and June in 2012 from a total of five television
channels most popular with children in Xi'an. Pearson chi (2) tests and logistic
regression were applied to determine differences in the proportion of healthy
food, unhealthy food and miscellaneous food advertisements for different
channels, programs, dates, viewing periods and the use of persuasive marketing
tactics. RESULTS: Of the 5527 advertisements transcribed, 25.5 % were for food,
among which 48.1 % were considered to be unhealthy. The frequency of food
advertisements was 6 per hour per channel, including 3 unhealthy food
advertisements. Compared with healthy and miscellaneous food advertisements, more
unhealthy food advertisements were shown during afternoon, weekends and
children's non-peak viewing times as well as on children's television channels,
central television channels and non-children's programmes. Unhealthy foods
contributed the highest proportion of all food advertisements containing
promotional characters (51.7 %) and premium offers (59.1 %). Both promotional
characters and premium offers appeared more on non-children's television
channels. CONCLUSIONS: The majority of food advertisements were for unhealthy
food. More unhealthy food ads were shown in children's non-peak time and
afternoon as well as non-children's channels. More children-oriented persuasive
marketing tactics were used in unhealthy food ads especially in non-children's
channels. Therefore, intervening in the entrance of unhealthy foods into the
market and establishing regulations related to food advertising especially
unhealthy food advertisements are important strategies to prevent children's
exposure to unhealthy food and childhood obesity.
PMID- 27515013
TI - Water quality following extensive beetle-induced tree mortality: Interplay of
aromatic carbon loading, disinfection byproducts, and hydrologic drivers.
AB - The recent bark beetle epidemic across western North America may impact water
quality as a result of elevated organic carbon release and hydrologic shifts
associated with extensive tree dieback. Analysis of quarterly municipal
monitoring data from 2004 to 2014 with discretization of six water treatment
facilities in the Rocky Mountains by extent of beetle impact revealed a
significant increasing trend in total organic carbon (TOC) and total
trihalomethane (TTHM) production within high (?50% areal infestation) beetle
impacted watersheds while no or insignificant trends were found in watersheds
with lower impact levels. Alarmingly, the TTHM concentration trend in the high
impact sites exceeded regulatory maximum contaminant levels during the most
recent two years of analysis (2013-14). To evaluate seasonal differences, explore
the interplay of water quality and hydrologic processes, and eliminate
variability associated with municipal reporting, these treatment facilities were
targeted for more detailed surface water sampling and characterization. Surface
water samples collected from high impact watersheds exhibited significantly
higher TOC, aromatic signatures, and disinfection byproduct (DBP) formation
potential than watersheds with lower infestation levels. Spectroscopic analyses
of surface water samples indicated that these heightened DBP precursor levels are
a function of both elevated TOC loading and increased aromatic character. This
association was heightened during precipitation and runoff events in high impact
sites, supporting the hypothesis that altered hydrologic flow paths resulting
from tree mortality mobilize organic carbon and elevate DBP formation potential
for several months after runoff ceases. The historical trends found here likely
underestimate the full extent of TTHM shifts due to monitoring biases with the
extended seasonal release of DBP precursors increasing the potential for human
exposure. Collectively, our analysis suggests that while water quality impacts
continue to rise nearly one decade after infestation, significant increases in
TOC mobilization and DBP precursors are limited to watersheds that experience
extensive tree mortality.
PMID- 27515014
TI - Effects of hydro- and thermopeaking on benthic macroinvertebrate drift.
AB - The operation of storage hydropower plants is commonly linked to frequent
fluctuations in discharge and water level (hydropeaking) of downstream river
stretches and is often accompanied by cooling or warming of the water body
downstream (cold or warm thermopeaking, respectively). The objective of this
study is to assess the single and combined effects of hydropeaking and cold
thermopeaking on the drift of selected aquatic macroinvertebrates in experimental
flumes. The study specifically aims to (1) investigate the macroinvertebrate
drift induced by hydropeaking, (2) identify taxon-specific drift patterns
following combined hydropeaking and cold thermopeaking and (3) quantify diurnal
drift differences under both impact types. Overall, hydropeaking induced
significantly higher drift rates of most macroinvertebrate taxa. Combined
hydropeaking and cold thermopeaking, however, revealed reduced total drift rates,
however with strong taxon-specific response patterns. Hydropeaking during night
led to significantly higher drift rates than during daytime, while in combination
with thermopeaking the same trend was observable, although insignificant. Taxon
specific analysis revealed lower drift rates following hydropeaking for
rheophilic and interstitial taxa (e.g. Leuctra sp., Hydropsyche sp.), whereas
many limnophilic taxa adapted to low current showed markedly increased drift
(e.g. Lepidostoma hirtum and Leptoceridae). In line with previous studies, our
results confirm a significant loss of limnophilic macroinvertebrate taxa
following hydraulic stress. The mitigating effect of cold thermopeaking might be
explained by behavioural patterns, but requires further investigation to clarify
if macroinvertebrates actively avoid drift and intrude into the interstitial,
when cold water is discharged. Our results imply that river restoration projects
must address the hydrological regime and, if necessary need to include suitable
management schemes for hydropower plants. Besides operative management measures,
the construction of reservoirs to buffer hydropeaks or the diversion of
hydropeaks into larger water bodies could mitigate hydropeaking effects and
foster biological recovery including limnophilic taxa.
PMID- 27515015
TI - Groundwater flow and geochemical evolution in the Central Flinders Ranges, South
Australia.
AB - The chemical characteristics of water in the Oratunga Area, Central Flinders
Ranges, South Australia have been used to evaluate and determine the processes
controlling water chemistry in addition to the sources of ions. The isotopic
analysis results show that the groundwater is mainly meteoric. Based on the rock
and water chemistry, ionic ratios, hydrochemical facies and saturation indices,
the chemical evolution has been studied. The chemistry of groundwater revealed
two types of water. Thus, in high topographic areas, low TDS, bicarbonate and
mixed water types are dominated and support a rapid and direct recharge. While in
the low topographic areas, high TDS and chloride compositions are the most common
attributed to the accumulation of ions and groundwater evolution. Analysis of the
ion concentration, head data and saturation indices shows a compositional trend
that can be studied as an evolutionary system. The ionic ratios and
hydrogeochemical modelling using NETPATH was used to quantify and verify the
different hydrochemical processes. The resulting data shows that calcite
dissolution/precipitation and cation exchange reactions are the major processes
affecting groundwater chemical evolution of the groundwater in the basin. This
study has provided a basis for a better understanding of the hydrogeologic
setting in areas of a little data.
PMID- 27515016
TI - Dust levels of polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo
p-dioxins/furans (PBDD/Fs) in the Taiwanese elementary school classrooms:
Assessment of the risk to school-age children.
AB - Elementary school classroom dust is an important source of exposure to
polybrominated dibenzo-p-dioxins/furans and diphenyl ethers (PBDD/DF/DEs) for
school-age children. Our goal is thus to investigate concentrations of
PBDD/DF/DEs in elementary school classroom dust to further assess the impact on
school-age children via ingestion. The dust from classrooms, including both
normal (NR) and computer classrooms (CR), was collected from six urban and four
rural schools. Fourteen PBDEs and twelve PBDD/Fs were measured using high
resolution gas-chromatography/high-resolution mass-spectrometry. The mean levels
of Sigma14PBDEs in NR and CR dust from the urban classrooms were 370 and 2510ng/g
and those whose dust from the rural classrooms were 464 and 1780ng/g. The means
of SigmaPBDD/Fs were 0.0401ng-WHO2005-TEQ/g (concentration: 4.72ng/g) in urban NR
dust, 0.0636ng-WHO2005-TEQ/g (7.51ng/g) in urban CR dust, 0.0281ng-WHO2005TEQ/g
(3.60ng/g) in rural NR dust, and 0.0474ng-WHO2005TEQ/g (6.28ng/g) in rural CR
dust. The PBDEs pattern in NR dust was quite different from that in CR dust, but
the PBDD/Fs patterns in NR and CR dust were similar. A linearly significant
correlation coefficient (n=20, r=0.862, p<0.001) was found between SigmaPBDEs and
SigmaPBDD/Fs in NR and CR dust, indicating that the PBDEs and PBDD/Fs in the dust
may be from the same sources in the elementary school classrooms. This study
assessed the risks (daily intake and cancer and non-cancer risks) of PBDEs and
PBDD/Fs for the children from the classroom dust, and the calculated risk values
did not exceed the related thresholds. With regard to the exposure scenarios for
school-age children in an indoor environment, the results suggest that they might
ingest more dust PBDD/DF/DEs in their homes than in the schools. In conclusion,
the exposure of Taiwanese elementary school children to PBDD/DF/DEs via indoor
dust was with a safe range based on our findings.
PMID- 27515017
TI - The changing prevalence of pulmonary infection in adults with cystic fibrosis: A
longitudinal analysis.
AB - BACKGROUND: Increased patient longevity and aggressive antibiotic treatment are
thought to impact on the microbial composition of the airways of adults with
cystic fibrosis (CF). In this study, we sought to determine if a temporal change
in the airway microbiology of adults with CF has occurred over time. METHODS:
Longitudinal analysis of sputum microbiology results was undertaken on patients
attending a large adult CF centre. Clinical status and health outcomes of
transitioning patients were also assessed. RESULTS: A decrease in the prevalence
of Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia complex
and Aspergillus spp. (p=0.001, p<0.001, p=0.002 and p<0.001, respectively)
occurred. Improvements in lung function among transitioning patients infected
with P. aeruginosa were observed. CONCLUSION: Overtime, a decline in the
prevalence of many CF airway pathogens has occurred. Significantly, an
incremental improvement in lung function was reported for transitioning patients
with current P. aeruginosa infections.
PMID- 27515018
TI - Decreasing age at first anal intercourse among men who have sex with men in
China: a multicentre cross-sectional survey.
AB - INTRODUCTION: Literature on the age at first anal intercourse (AFAI) among men
who have sex with men (MSM) is limited. We aimed to elucidate the evolution of
AFAI and the factors associated with early AFAI, based on a large sample of MSM
in China. METHODS: We collected information on the demographics and sexual
behaviours of MSM from seven large cities in China from 2012 to 2013. Blood
samples were collected for HIV serology. AFAI was calculated for MSM born in
different time periods. Linear regression models were used to explore factors
associated with younger AFAI. RESULTS: A total of 4491 MSM (median age: 27 years,
median AFAI: 21 years) were recruited. Median AFAI decreased steadily from 33
years of age among MSM born from 1940 to 1959 to 18 years of age among MSM born
from 1990 to 1996. Factors significantly associated with younger AFAI included
more recent birth cohort, being unmarried or living with a male partner, being a
student or industry worker, the gender of the first partner being male, and using
Rush or Ecstasy in the past six months (p for all <0.05). CONCLUSIONS: AFAI among
MSM in China has considerably decreased over the past few decades. The decreasing
AFAI and factors associated with younger AFAI point to the necessity of early sex
education and control of recreational drug use among MSM in China.
PMID- 27515019
TI - Is it time to combine untargeted antifungal strategies to reach the goal of
'early' effective treatment?
PMID- 27515021
TI - Trajectories of cannabis use disorder: risk factors, clinical characteristics and
outcomes.
AB - AIMS: To estimate cannabis use disorder (CUD) trajectory classes from ages 14 to
30 years and compare classes on clinical characteristics, risk factors and
psychosocial outcomes. DESIGN: Four waves (T1-T4) of data from an epidemiological
study of psychopathology among a regionally representative sample. Trajectory
classes described risk for CUD as a function of age. The number of classes was
determined by model fit. SETTING: Participants were selected randomly from nine
high schools in western Oregon, USA. PARTICIPANTS: The sample included 816
participants [age at T1 mean = 16.6, standard deviation (SD) = 1.2; 44% male; 8%
non-white]. MEASUREMENTS: Participants completed diagnostic interviews, Child
Trauma Questionnaire, Social Adjustment Scale and items adapted from the
Wisconsin Manual for Assessing Psychotic-Like Experiences. FINDINGS: There were
three CUD trajectory classes (Lo-Mendell-Rubin likelihood ratio test < 0.001):
(1) persistent increasing risk; (2) maturing out, with increasing risk then
decreasing risk; and (3) stable low risk. The persistent increasing class had
later initial CUD onsets (eta2 = 0.16, P < 0.001) and greater cumulative CUD
durations (eta2 = 0.26, P < 0.001). Male sex [odds ratio (OR) = 2.57, P =
0.018], externalizing disorders between ages 24 and 30 years (OR = 2.64, P <
0.001) and psychotic experiences during early adulthood (Cohen's d = 0.44, P =
0.016) discriminated between the persistent increasing and the maturing-out
classes. CONCLUSIONS: Evidence suggests three distinguishable types of trajectory
for development of cannabis use disorder starting in early teens: (1) persistent
increasing risk; (2) maturing out, with increasing risk then decreasing risk; and
(3) stable low risk.
PMID- 27515022
TI - Mapping gains and losses in woody vegetation across global tropical drylands.
AB - Woody vegetation in global tropical drylands is of significant importance for
both the interannual variability of the carbon cycle and local livelihoods.
Satellite observations over the past decades provide a unique way to assess the
vegetation long-term dynamics across biomes worldwide. Yet, the actual changes in
the woody vegetation are always hidden by interannual fluctuations of the leaf
density, because the most widely used remote sensing data are primarily related
to the photosynthetically active vegetation components. Here, we quantify the
temporal trends of the nonphotosynthetic woody components (i.e., stems and
branches) in global tropical drylands during 2000-2012 using the vegetation
optical depth (VOD), retrieved from passive microwave observations. This is
achieved by a novel method focusing on the dry season period to minimize the
influence of herbaceous vegetation and using MODerate resolution Imaging
Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) data to
remove the interannual fluctuations of the woody leaf component. We revealed
significant trends (P < 0.05) in the woody component (VODwood ) in 35% of the
areas characterized by a nonsignificant trend in the leaf component (VODleaf
modeled from NDVI), indicating pronounced gradual growth/decline in woody
vegetation not captured by traditional assessments. The method is validated using
a unique record of ground measurements from the semiarid Sahel and shows a strong
agreement between changes in VODwood and changes in ground observed woody cover
(r2 = 0.78). Reliability of the obtained woody component trends is also
supported by a review of relevant literatures for eight hot spot regions of
change. The proposed approach is expected to contribute to an improved assessment
of, for example, changes in dryland carbon pools.
PMID- 27515023
TI - Framework Design and Influencing Factor Analysis of a Water Environmental
Functional Zone-Based Effluent Trading System.
AB - The efficacy of traditional effluent trading systems is questionable due to their
neglect of seasonal hydrological variation and the creation of upstream hot spots
within a watershed. Besides, few studies have been conducted to distinguish the
impacts of each influencing factor on effluent trading systems outputs. In this
study, a water environmental functional zone-based effluent trading systems
framework was configured and a comprehensive analysis of its influencing factors
was conducted. This proposed water environmental functional zone-based effluent
trading systems was then applied for the control of chemical oxygen demand in the
Beiyun River watershed, Beijing, China. Optimal trading results highlighted the
integration of water quality constraints and different hydrological seasons,
especially for downstream dischargers. The optimal trading of each discharger, in
terms of pollutant reduction load and abatement cost, is greatly influenced by
environmental and political factors such as background water quality, the
location of river assessment points, and tradable discharge permits. In addition,
the initial permit allowance has little influence on the market as a whole but
does impact the individual discharger. These results provide information that is
critical to understanding the impact of policy design on the functionality of an
effluent trading systems.
PMID- 27515024
TI - Does Wyoming's Core Area Policy Protect Winter Habitats for Greater Sage-Grouse?
AB - Conservation reserves established to protect important habitat for wildlife
species are used world-wide as a wildlife conservation measure. Effective
reserves must adequately protect year-round habitats to maintain wildlife
populations. Wyoming's Sage-Grouse Core Area policy was established to protect
breeding habitats for greater sage-grouse (Centrocercus urophasianus). Protecting
only one important seasonal habitat could result in loss or degradation of other
important habitats and potential declines in local populations. The purpose of
our study was to identify the timing of winter habitat use, the extent which
individuals breeding in Core Areas used winter habitats, and develop resource
selection functions to assess effectiveness of Core Areas in conserving sage
grouse winter habitats in portions of 5 Core Areas in central and north-central
Wyoming during winters 2011-2015. We found that use of winter habitats occured
over a longer period than current Core Area winter timing stipulations and a
substantial amount of winter habitat outside of Core Areas was used by
individuals that bred in Core Areas, particularly in smaller Core Areas. Resource
selection functions for each study area indicated that sage-grouse were selecting
habitats in response to landscapes dominated by big sagebrush and flatter
topography similar to other research on sage-grouse winter habitat selection. The
substantial portion of sage-grouse locations and predicted probability of
selection during winter outside small Core Areas illustrate that winter
requirements for sage-grouse are not adequately met by existing Core Areas.
Consequently, further considerations for identifying and managing important
winter sage-grouse habitats under Wyoming's Core Area Policy are warranted.
PMID- 27515025
TI - Characterization of a panARS-based episomal vector in the methylotrophic yeast
Pichia pastoris for recombinant protein production and synthetic biology
applications.
AB - BACKGROUND: Recombinant protein production in the methylotrophic yeast Pichia
pastoris largely relies on integrative vectors. Although the stability of
integrated expression cassettes is well appreciated for most applications, the
availability of reliable episomal vectors for this host would represent a useful
tool to expedite cloning and high-throughput screening, ameliorating also the
relatively high clonal variability reported in transformants from integrative
vectors caused by off-target integration in the P. pastoris genome. Recently,
heterologous and endogenous autonomously replicating sequences (ARS) were
identified in P. pastoris by genome mining, opening the possibility of expanding
the available toolbox to include efficient episomal plasmids. The aim of this
technical report is to validate a 452-bp sequence ("panARS") in context of P.
pastoris expression vectors, and to compare their performance to classical
integrative plasmids. Moreover, we aimed to test if such episomal vectors would
be suitable to sustain in vivo recombination, using fragments for transformation,
directly in P. pastoris cells. RESULTS: A panARS-based episomal vector was
evaluated using blue fluorescent protein (BFP) as a reporter gene. Normalized
fluorescence from colonies carrying panARS-BFP outperformed the level of signal
obtained from integrative controls by several-fold, whereas endogenous sequences,
identified from the P. pastoris genome, were not as efficient in terms of protein
production. At the single cell level, panARS-BFP clones showed lower interclonal
variability but higher intraclonal variation compared to their integrative
counterparts, supporting the idea that heterologous protein production could
benefit from episomal plasmids. Finally, efficiency of 2-fragment and 3-fragment
in vivo recombination was tested using varying lengths of overlapping regions and
molar ratios between fragments. Upon optimization, minimal background was
obtained for in vivo assembled vectors, suggesting this could be a quick and
efficient method to generate of episomal plasmids of interest. CONCLUSIONS: An
expression vector based on the panARS sequence was shown to outperform its
integrative counterparts in terms of protein productivity and interclonal
variability, facilitating recombinant protein expression and screening. Using
optimized fragment lengths and ratios, it was possible to perform reliable in
vivo recombination of fragments in P. pastoris. Taken together, these results
support the applicability of panARS episomal vectors for synthetic biology
approaches.
PMID- 27515026
TI - Potential role of herbal remedies in stem cell therapy: proliferation and
differentiation of human mesenchymal stromal cells.
AB - Stem cell therapy has revolutionized modern clinical therapy with the potential
of stem cells to differentiate into many different cell types which may help to
replace different cell lines of an organism. Innumerous trials are carried out to
merge new scientific knowledge and techniques with traditional herbal extracts
that may result in less toxic, affordable, and highly available natural
alternative therapeutics. Currently, mesenchyamal stromal cell (MSC) lines are
treated with individual and mixtures of crude herbal extracts, as well as with
purified compounds from herbal extracts, to investigate the mechanisms and
effects of these on stem cell growth and differentiation. Human MSCs (hMSCs)
possess multilineage, i.e., osteogenic, neurogenic, adipogenic, chondrogenic, and
myogenic, differentiation abilities. The proliferative and differentiation
properties of hMSCs treated with herbal extracts have shown promise in diseases
such as osteoporosis, neurodegenerative disorders, and other tissue degenerative
disorders. Well characterized herbal extracts that result in increased rates of
tissue regeneration may be used in both stem cell therapy and tissue engineering
for replacement therapy, where the use of scaffolds and vesicles with enhanced
attaching and proliferative properties could be highly advantageous in the
latter. Although the clinical application of herbal extracts is still in progress
due to the variability and complexity of bioactive constituents, standardized
herbal preparations will strengthen their application in the clinical context. We
have critically reviewed the proliferative and differentiation effects of
individual herbal extracts on hMSCs mainly derived from bone marrow and
elaborated on the plausible underlying mechanisms of action. To be fruitfully
used in reparative and regenerative therapy, future directions in this area of
study should (i) make use of hMSCs derived from different non-traditional
sources, including medical waste material (umbilical cord, Wharton's jelly, and
placenta), (ii) take account of the vast numbers of herbal extracts used in
traditional medicine globally, and (iii) investigate the mechanisms and pathways
of their effects on hMSCs.
PMID- 27515027
TI - Metronomic cyclophosphamide activation of anti-tumor immunity: tumor model, mouse
host, and drug schedule dependence of gene responses and their upstream
regulators.
AB - BACKGROUND: Cyclophosphamide (CPA) can activate immunogenic tumor cell death,
which induces immune-based tumor ablation and long-term anti-tumor immunity in a
syngeneic C57BL/6 (B6) mouse GL261 glioma model when CPA is given on a 6-day
repeating metronomic schedule (CPA/6d). In contrast, we find that two other
syngeneic B6 mouse tumors, LLC lung carcinoma and B16F10 melanoma, do not exhibit
these drug-induced immune responses despite their intrinsic sensitivity to CPA
cytotoxicity. METHODS: To elucidate underlying mechanisms, we investigated gene
expression and molecular pathway changes associated with the disparate immune
responsiveness of these tumors to CPA/6d treatment. RESULTS: Global transcriptome
analysis indicated substantial elevation of basal GL261 immune infiltration and
strong CPA/6d activation of GL261 immune stimulatory pathways and their upstream
regulators, but without preferential depletion of negative immune regulators
compared to LLC and B16F10 tumors. In LLC tumors, where CPA/6d treatment is shown
to be anti-angiogenic, CPA/6d suppressed VEGFA target genes and down regulated
cell adhesion and leukocyte transendothelial migration genes. In GL261 tumors
implanted in adaptive immune-deficient scid mice, where CPA/6d-induced GL261
regression is incomplete and late tumor growth rebound can occur, T cell receptor
signaling and certain cytokine-cytokine receptor responses seen in B6 mice were
deficient. Extending the CPA treatment interval from 6 to 9 days (CPA/9d) - which
results in a strong but transient natural killer cell response followed by early
tumor growth rebound - induced fewer cytokines and increased expression of drug
metabolism genes. CONCLUSIONS: These findings elucidate molecular response
pathways activated by intermittent metronomic CPA treatment and identify
deficiencies that characterize immune-unresponsive tumor models and drug
schedules.
PMID- 27515028
TI - Prognostic significance of preoperative serum Krebs von den Lungen-6 level in non
small cell lung cancer.
AB - OBJECTIVES: We retrospectively analyzed the prognostic significance of
preoperative serum Krebs von den Lungen-6 (KL-6) level in non-small cell lung
cancer (NSCLC) patients. METHODS: We enrolled 175 NSCLC patients who underwent
curative surgery between 2009 and 2011. We subdivided the patients into 2 groups:
with and without interstitial lung disease (ILD). Prognostic significance of
serum KL-6 level was examined. RESULTS: The 5-year survival of patients with high
serum KL-6 level was poor. Multivariate analysis also revealed the prognostic
significance of serum KL-6 level. Serum KL-6 level was also a prognostic factor
for patients without ILD. Although the number of patients with ILD was small, in
patients with ILD, there was a trend towards an association between serum KL-6
level and patients' prognosis but this did not reach statistical significance.
CONCLUSIONS: Serum KL-6 level is a prognostic factor for resected NSCLC patients,
especially patients without ILD. There is a possibility that serum KL-6 level is
a prognostic marker regardless of the presence of ILD.
PMID- 27515030
TI - Compensation for visually specified coarticulation in liquid-stop contexts.
AB - The question of whether speech perceivers use visual coarticulatory information
in speech perception remains unanswered, despite numerous past studies. Across
different coarticulatory contexts, studies have both detected (e.g., Mitterer in
Perception & Psychophysics, 68, 1227-1240, 2006) and failed to detect (e.g.,
Vroomen & de Gelder in Language and Cognitive Processes, 16, 661-672. doi:
10.1080/01690960143000092 , 2001) visual effects. In this study, we focused on a
liquid-stop coarticulatory context and attempted to resolve the contradictory
findings of Fowler, Brown, and Mann (Journal of Experimental Psychology: Human
Perception and Performance, 26, 877-888. doi: 10.1037/0096-1523.26.3.877 , 2000)
and Holt, Stephens, and Lotto (Perception & Psychophysics, 67, 1102-1112. doi:
10.3758/BF03193635 , 2005). We used the original stimuli of Fowler et al. with
modifications to the experimental paradigm to examine whether visual compensation
can occur when acoustic coarticulatory information is absent (rather than merely
ambiguous). We found that perceivers' categorizations of the target changed when
coarticulatory information was presented visually using a silent precursor,
suggesting that visually presented coarticulatory information can induce
compensation. However, we failed to detect this effect when the same visual
information was accompanied by an ambiguous auditory precursor, suggesting that
these effects are weaker and less robust than auditory compensation. We discussed
why this might be the case and examined implications for accounts of
coarticulatory compensation.
PMID- 27515031
TI - Predicting the sensory consequences of one's own action: First evidence for
multisensory facilitation.
AB - Predicting the sensory consequences of our own actions contributes to efficient
sensory processing and might help distinguish the consequences of self- versus
externally generated actions. Previous research using unimodal stimuli has
provided evidence for the existence of a forward model, which explains how such
sensory predictions are generated and used to guide behavior. However, whether
and how we predict multisensory action outcomes remains largely unknown. Here, we
investigated this question in two behavioral experiments. In Experiment 1, we
presented unimodal (visual or auditory) and bimodal (visual and auditory) sensory
feedback with various delays after a self-initiated buttonpress. Participants had
to report whether they detected a delay between their buttonpress and the
stimulus in the predefined task modality. In Experiment 2, the sensory feedback
and task were the same as in Experiment 1, but in half of the trials the action
was externally generated. We observed enhanced delay detection for bimodal
relative to unimodal trials, with better performance in general for actively
generated actions. Furthermore, in the active condition, the bimodal advantage
was largest when the stimulus in the task-irrelevant modality was not delayed
that is, when it was time-contiguous with the action-as compared to when both the
task-relevant and task-irrelevant modalities were delayed. This specific
enhancement for trials with a nondelayed task-irrelevant modality was absent in
the passive condition. These results suggest that a forward model creates
predictions for multiple modalities, and consequently contributes to multisensory
interactions in the context of action.
PMID- 27515032
TI - An Analysis of Operative Experiences of Junior General Surgical Residents and
Correlation With the SCORE Curriculum.
AB - OBJECTIVE: Junior surgical resident education at academic institutions is
traditionally focused to preoperative and postoperative patient management. Our
objective was to investigate the number and type of surgical procedures performed
by junior general surgery residents in comparison with the American Board of
Surgery requirements and the Surgical Council on Resident Education (SCORE)
curriculum. DESIGN: This was a retrospective study using the Accreditation
Counsel for Graduate Medical Education (ACGME) operative case logs of junior
surgical residents. SETTING: The Ohio State University Wexner Medical Center,
Columbus, OH; a tertiary academic medical center. PARTICIPANTS: We performed, an
institutional review board approved, retrospective review of logged surgical
cases from general surgical residents during postgraduate year (PGY) 1 and 2 from
2009 to 2015 at an academic medical center. Summary case logs were accessed from
the ACGME. Procedures were extracted from the SCORE curriculum and correlated to
corresponding ACGME defined procedures for total cases, major cases, and
endoscopy. Minor cases and patient care cases were excluded as they were not
clearly defined on the category report. SCORE procedures were excluded if there
was not a corresponding ACGME procedure on the summary report. SCORE procedures
and ACGME procedures were combined with each other if there was overlap with
correlation. Statistics were performed on individual and total resident data. One
sample student's t-test was used to compare total number of cases logged with the
250 case log ABS requirement and to compare the total major cases and endoscopy
performed with those represented on SCORE. RESULTS: Overall, 26 residents
completed both PGY-1 and 2 years from 2009 to 2015, and remained at the same
institution for case logs to be accessed during the study period. A total of 21
residents (80.76%) completed 250 cases or more after their first 2 years of
residency. Across all years, the mean case log was 349 cases (p = 0.20), and was
statistically more than than 250 cases in 3 of the 5 class years. Junior
residents completed a total mean of 312 major and endoscopy cases (89%) at the
end of 2 years, which was statistically higher than the 75% testing hypothesis
across all years (p < 0.01). Of major and endoscopy cases performed in total by
the completion of the PGY-2 year, a mean of 275 cases (88%) were included in the
SCORE curriculum. Using one-sample t-test, SCORE procedures represented more than
85% of the major and endoscopy cases logged (p < 0.01). Of all major and
endoscopy cases logged that correlate to a SCORE procedure, 95% were found to be
"core" and 5% were "advanced." CONCLUSIONS: Our study demonstrates that junior
surgical residents meet the 250 case log requirement put forth by the ABS, and
most major procedures and endoscopy performed correspond with the core cases of
the SCORE curriculum at our institution. This study aid in the confirmation of
the SCORE curriculum for junior residents, and those procedures which should be
designated as core.
PMID- 27515029
TI - Therapies for Parkinson's diseases: alternatives to current pharmacological
interventions.
AB - Parkinson's disease (PD) is the second most common neurodegenerative disorder
caused by the selective and progressive loss of dopaminergic neurons in the
substantia nigra pars compacta. Although PD has been heavily researched, the
precise etiology and pathogenesis for PD are still inconclusive. Consequently,
current pharmacological treatments for PD are largely symptomatic rather than
preventive and there is still no cure for this disease nowadays. Moreover,
nonmotor symptoms caused by intrinsic PD pathology or side effects induced by
currently used pharmacological interventions are gaining increasing attention and
urgently need to be treated due to their influence on quality of life. As ancient
traditional healing systems, Tai Chi, Yoga, acupuncture and natural products have
long been considered as complementary or alternative therapeutic options for PD.
Recently, several newly developed non-pharmacological therapeutic strategies,
including deep brain stimulation, repetitive transcranial magnetic stimulation,
near-infrared light, gene therapy and cell replacement therapy, have also been
suggested to give benefits to relieve parkinsonian symptoms. This review will
summarize and update the therapeutic potential and the most recent research
progresses of these traditional and modern therapeutic options and highlight
their clinical meaning for the therapy of not only PD but also other
neurodegenerative diseases.
PMID- 27515034
TI - Prevalence of prehypertension and associated risk factors among Chinese adults
from a large-scale multi-ethnic population survey.
AB - BACKGROUND: Up to date, most of previous studies about Chinese prehypertension
were conducted based on a small sample or in only one province, which could not
represent the general population in China. Furthermore, no information on the
ethnic difference in prevalence of prehypertension has been reported in China.
The aim of this study is to examine the sex-specific, age-specific and ethnic
specific prevalence of prehypertension and associated risk factors in a large
scale multi-ethnic Chinese adult population. METHODS: The subjects came from a
large-scale population survey about Chinese physiological constants and health
conditions conducted in six provinces. 47, 495 adults completed blood pressure
measurement. Prehypertension was defined as not being on antihypertensive
medications and having SBP of 120-139 mmHg and/or DBP of 80-89 mmHg. Odds ratio
(OR) and its 95 % confidence interval (CI) from logistic models were used to
reflect the prevalence of prehypertension. RESULTS: The mean age of all subjects
was 43.9 +/- 16.8 years. The prevalence of hypertension and prehypertension for
all them was 29.5 and 36.4 %, respectively. The prevalence of hypertension and
prehypertension for males (33.2 and 41.1 %, respectively) was higher than that
for females (27.0 and 33.2 %, respectively), and P < 0.001. The mean age of the
subjects was 54.8 +/- 14.0 years for hypertensive, 44.0 +/- 16.0 years for
prehypertensive and 35.3 +/- 14.5 years for normotensive. With aging, subjects
had more odds of getting prehypertension. Multivariate logistic model indicated
that males (OR = 2.076, 95 % CI: 1.952-2.208), laborers with mental work (OR =
1.084, 95 % CI: 1.020-1.152), Yi (OR = 1.347, 95 %CI: 1.210-1.500) and Hui
subjects (OR = 1.133, 95 % CI: 1.024-1.253), alcohol drinkers (OR = 1.147, 95 %
CI: 1.072-1.228), the generally obese (OR = 2.460, 95 % CI: 2.190-2.763), the
overweight (OR = 1.667, 95 % CI: 1.563-1.788), the abdominally obese (OR = 1.371,
95 % CI: 1.280-1.467) and subjects with family history of cardiovascular diseases
(OR = 1.132, 95 % CI: 1.045-1.226) had higher prevalence of prehypertension.
Subjects with higher educational level (OR = 0.687, 95 % CI: 0.627-0.752 for
university) and Miao (OR = 0.753, 95 % CI: 0.623-0.910), Tibetan (OR = 0.521, 95
% CI: 0.442-0.613), Tujia (OR = 0.779, 95 % CI: 0.677-0.898) subjects had lower
prevalence. CONCLUSION: High prevalence rate of prehypertension was general in
Chinese adults. Many sociodemographic characteristics were significantly
associated with prehypertension. There were important clinical significance and
public health significance about age-specific, gender-specific and ethnic
specific Chinese prehypertension conditions studies.
PMID- 27515035
TI - Convulsions with Gastroenteritis: Reflections on some Cases and Tentative
Diagnostic Score.
AB - BACKGROUND: Since 1980 a form of benign convulsion during mild gastroenteritis,
called Convulsion With Gastroenteritis (CWG) has been described. However
diagnostic criteria have not been well defined yet given the similarity of CWG
with other diseases of young age and therefore diagnosis is done by exclusion,
creating anxiety in parents. OBJECTIVE AND METHODS: We here report a series of
cases admitted at our hospital and, making a review analysis of data available,
propose a diagnostic score (CWGDS) in order to rapidly individuate the disease
from history. RESULTS: Five cases of seizures associated to gastrointestinal
symptoms were admitted to the Pediatric Unit of Eastern Liguria Hospital in La
Spezia from January 2014 to April 2015. All these cases could be defined as CWG
given their characteristics and benign evolution. We then prepared CWGDS from
literature's data and compared our cases with the score itself, having 100%
agreement between clinical diagnosis and diagnosis done by CWGDS. CONCLUSION: We
propose a diagnostic score to help the clinician in diagnosing a benign condition
such as CWG therefore avoiding as much as possible invasive procedures and
reassuring parents.
PMID- 27515036
TI - Intrauterine Intervention for the Treatment of Fetal Growth Restriction.
AB - Fetal growth restriction (FGR) is associated with an increased incidence of fetal
and neonatal death, and of neonatal morbidity. Babies born following FGR also are
at risk of a range of postnatal complications, which may contribute to an
increased incidence of disease later in life. There currently are no effective
clinical interventions which improve perinatal survival, intrauterine growth and
later outcomes of the FGR baby. Postnatal interventions aimed at promoting or
accelerating growth in FGR babies to improve outcome, particularly
neurodevelopmental outcomes, may further increase the risk of metabolic
dysregulation and, therefore, the risk of developing chronic disease in
adulthood. An intrauterine intervention to improve nutrition and growth in the
FGR fetus may have the potential to decrease mortality and improve long-term
outcomes by delaying preterm delivery and mitigating the need for and risks of
accelerated postnatal growth.
PMID- 27515033
TI - Advances in TRH signaling.
AB - The activity of the hypothalamus-pituitary-thyroid axis (HPT) is coordinated by
hypophysiotropic thyrotropin releasing hormone (TRH) neurons present in the
paraventricular nucleus of the hypothalamus. Hypophysiotropic TRH neurons act as
energy sensors. TRH controls the synthesis and release of thyrotropin, which
activates the synthesis and secretion of thyroid hormones; in target tissues,
transporters and deiodinases control their local availability. Thyroid hormones
regulate many functions, including energy homeostasis. This review discusses
recent evidence that covers several aspects of TRH role in HPT axis regulation.
Knowledge about the mechanisms of TRH signaling has steadily increased. New
transcription factors engaged in TRH gene expression have been identified, and
advances made on how they interact with signaling pathways and define the
dynamics of TRH neurons response to acute and/or long-term influences. Albeit yet
incomplete, the relationship of TRH neurons activity with positive energy balance
has emerged. The importance of tanycytes as a central relay for the feedback
control of the axis, as well as for HPT responses to alterations in energy
balance, and other stimuli has been reinforced. Finally, some studies have
started to shed light on the interference of prenatal and postnatal stress and
nutrition on HPT axis programing, which have confirmed the axis susceptibility to
early insults.
PMID- 27515037
TI - Development and validation of an Onchocerca ochengi microfilarial hamster model
for onchocerciasis drug screens.
AB - BACKGROUND: Onchocerciasis, caused by the parasitic nematode, Onchocerca volvulus
afflicts some 37 million people worldwide, and is the second leading infectious
cause of blindness globally. The only currently recommended drug for treatment of
the disease, ivermectin, is only microfilaricidal and has serious adverse effects
in individuals co-infected with high loads of Loa loa microfilariae (mf),
prompting the search for new and better drugs. Onchocerciasis drug discovery
studies have so far been based on in vivo models using Onchocerca species which
are not the closest to O. volvulus, and which may therefore, not adequately mimic
the natural infection in humans. Therefore, this study was carried out to develop
a better drug screening model for onchocerciasis, based on the use of cow-derived
O. ochengi, the closest known relative of O. volvulus. METHODS: Mf of O. ochengi
were injected subcutaneously at the nape of Syrian hamsters (Mesocricetus
auratus) and BALB/c mice. The skin, and especially the earlobes of the animals
were examined for mf 15-31 days after infection. For selected model validation,
the hamsters were treated with ivermectin at 150 or 600 MUg/kg body weight and
examined 30 days after infection for mf. For L. loa studies in hamsters, isolated
mf were injected intraperitoneally and animal organs were examined on day 26 for
mf. RESULTS: The Syrian hamsters were found to be the more permissive to O.
ochengi mf as fully viable mf were recovered from them on day 30, compared to
BALB/c mice where such mf were recovered on day 15, but not 30. However, both
animals were not permissive to L. loa mf even by day 15. Interestingly, more than
50 % of the total O. ochengi mf recovered were from the earlobes. The number of
mf injected was directly proportional to the number recovered. Ivermectin at both
concentrations tested completely eliminated the O. ochengi mf from the hamsters.
CONCLUSION: This study reveals the Syrian hamster as an appropriate small animal
model for screening of novel compounds against O. ochengi, the closest known
relative of O. volvulus.
PMID- 27515038
TI - Can a central blood volume deficit be detected by systolic pressure variation
during spontaneous breathing?
AB - BACKGROUND: Whether during spontaneous breathing arterial pressure variations
(APV) can detect a volume deficit is not established. We hypothesized that
amplification of intra-thoracic pressure oscillations by breathing through
resistors would enhance APV to allow identification of a reduced cardiac output
(CO). This study tested that hypothesis in healthy volunteers exposed to central
hypovolemia by head-up tilt. METHODS: Thirteen healthy volunteers were exposed to
central hypovolemia by 45 degrees head-up tilt while breathing through a
facemask with 7.5 cmH2O inspiratory and/or expiratory resistors. A brachial
arterial catheter was used to measure blood pressure and thus systolic pressure
variation (SPV), pulse pressure variation and stroke volume variation . Pulse
contour analysis determined stroke volume (SV) and CO and we evaluated whether
APV could detect a 10 % decrease in CO. RESULTS: During head-up tilt SV decreased
form 91 (+/-46) to 55 (+/-24) mL (mean +/- SD) and CO from 5.8 (+/-2.9) to 4.0
(+/-1.8) L/min (p < 0.05), while heart rate increased (65 (+/-11) to 75 (+/-13)
bpm; P < 0.05). Systolic pressure decreased from 127 (+/-14) to 121 (+/-13) mmHg
during head-up tilt, while SPV tended to increase (from 21 (+/-15)% to 30 (+/
13)%). Yet during head-up tilt, a SPV >= 37 % predicted a decrease in CO >= 10 %
with a sensitivity and specificity of 78 % and 100 %, respectively. CONCLUSION:
In spontaneously breathing healthy volunteers combined inspiratory and expiratory
resistors enhance SPV during head-up tilted induced central hypovolemia and allow
identifying a 10 % reduction in CO. Applying inspiratory and expiratory resistors
might detect a fluid deficit in spontaneously breathing patients. TRIAL
REGISTRATION: ClinicalTrials.gov number NCT02549482 Registered September 10(th)
2015.
PMID- 27515040
TI - Discovery of Camptothecin Based Topoisomerase I Inhibitors: Identification Using
an Atom Based 3D-QSAR, Pharmacophore Modeling, Virtual Screening and Molecular
Docking Approach.
AB - BACKGROUND: Camptothecin is a quinoline alkaloid, isolated from the Chinese tree
Camptotheca acuminate which exhibits its cytotoxic activity by the inhibition of
nuclear enzyme Topoisomerase I (topo I). Camptothecin and its analogues forms a
covalent bond with DNA which can arrest the tumor growth by slowing the
religation step of the enzyme and stabilize the covalent adduct between topo I
and DNA. Besides its strong anticancer potential, the limited solubility as well
as instability of the hydroxylactone ring (Ring E) limits the clinical
application of Camptothecin. This study was undertaken to identify novel
compounds having anticancer activity with mechanism of action similar to that of
Camptothecin using scaffold perception technique. MATERIALS AND METHODS: We
developed a common pharmacophore hypothesis using 32 camptothecin analogues,
which was used for preliminary screening of large databases (ZINC "drug-like"
database) to make sure, to include only compounds containing the key structural
features needed to be Topoisomerase I inhibitors. In terms of a structure based
approach, we systematically investigated various types of docking protocols to
identify the most active compounds from the identified hit molecules. A post
docking energy calculation was also carried out by MM/GBSA method. RESULTS: From
the selected series of camptothecin analogs, a 3D-QSAR pharmacophore model was
developed. The model consists of one acceptor site, one donor site, one
hydrophobic site and two aromatic functions (ADHRR). Then, the pharmacophore
model was employed as 3D search query to screen compounds from ZINC database
which followed by molecular docking study and MM/GBSA calculation identified 2
lead molecules which, however, were not biologically validated. In silico studies
reveals that the identified lead molecules have a better binding affinity than
the co crystallized ligand. CONCLUSION: The identified molecules were able to
bind to the active site of Topo-I enzyme similar to that of Camptothecin and the
ADME properties were within the acceptable range defined for human use. The new
molecules identified by virtual screening as such or on further optimization can
be used as potential leads in designing Topoisomerase I inhibitors.
PMID- 27515041
TI - High Throughput Screening: Developed Techniques for Cellulolytic and Xylanolytic
Activities Assay.
AB - High throughput screening (HTS) is a powerful tool in biotechnology. The search
for new or improved enzymes with suitable biochemical properties for industrial
processes, has resulted in high efforts and research activities to develop new
methodologies for activity screening. In this context, important advances have
been achieved for the screening of cellulases and xylanases activities from wild
and recombinant microorganisms, and from sequence databases. These enzymes have a
wide range of industrial applications, including food, animal feed, textile, pulp
and paper industries and detergents. Cellulases and xylanases along with
pectinases, represent 20% of the world enzyme market. Recently, cellulases and
xylanases have been used on fermentable sugars recovered from lignocellulosic
biomass for second-generation biorefineries, aimed to produce chemical and
biofuel platforms. As a result, HTS methods for biomass or biomass-degrading
enzymes are gaining importance. This article presents evidence of the studies
carried out for HTS of cellulase and xylanase activities.
PMID- 27515039
TI - Association of microRNA polymorphisms with the risk of head and neck squamous
cell carcinoma in a Chinese population: a case-control study.
AB - BACKGROUND: MicroRNA (miRNA) polymorphisms may alter miRNA-related processes, and
they likely contribute to cancer susceptibility. Various studies have
investigated the associations between genetic variants in several key miRNAs and
the risk of human cancers; however, few studies have focused on head and neck
squamous cell carcinoma (HNSCC) risk. This study aimed to evaluate the
associations between several key miRNA polymorphisms and HNSCC risk in a Chinese
population. METHODS: In this study, we genotyped five common single-nucleotide
polymorphisms (SNPs) in several key miRNAs (miR-149 rs2292832, miR-146a
rs2910164, miR-605 rs2043556, miR-608 rs4919510, and miR-196a2 rs11614913) and
evaluated the associations between these SNPs and HNSCC risk according to cancer
site with a case-control study including 576 cases and 1552 controls, which were
matched by age and sex in a Chinese population. RESULTS: The results revealed
that miR-605 rs2043556 [dominant model: adjusted odds ratio (OR) 0.71, 95%
confidence interval (CI) 0.58-0.88; additive model: adjusted OR 0.74, 95% CI 0.62
0.89] and miR-196a2 rs11614913 (dominant model: adjusted OR 1.36, 95% CI 1.08
1.72; additive model: adjusted OR 1.28, 95% CI 1.10-1.48) were significantly
associated with the risk of oral squamous cell carcinoma (OSCC). Furthermore,
when these two loci were evaluated together based on the number of putative risk
alleles (rs2043556 A and rs11614913 G), a significant locus-dosage effect was
noted on the risk of OSCC (P trend < 0.001). However, no significant association
was detected between the other three SNPs (miR-149 rs2292832, miR-146a rs2910164,
and miR-608 rs4919510) and HNSCC risk. CONCLUSION: Our study provided the
evidence that miR-605 rs2043556 and miR-196a2 rs11614913 may have an impact on
genetic susceptibility to OSCC in Chinese population.
PMID- 27515042
TI - Multiorgan transplantation.
AB - Kidney transplantation has proven to be the gold standard therapy for severe
chronic kidney disease (CKD) due to multiple etiologies in individuals deemed
eligible from a surgical standpoint. While kidney transplantation is
traditionally considered in conditions of native kidney disease such as diabetes
and immunological or inherited causes of kidney disease, an increasing indication
for kidney transplantation is kidney dysfunction in the setting of other severe
organ dysfunction that requires transplant, such as severe liver or heart
disease. In these settings, multiorgan transplantation is now commonly performed,
with controversy regarding the appropriate utilization of kidneys transplanted
both from a physiological perspective (distinguishing those who require a kidney
transplant) and also from an ethical perspective (allocation of a scarce resource
to a more morbid population). These issues persist in the setting of simultaneous
pancreas-kidney transplant (SPK), in which utilization for patients with type 1
diabetes has been historically accepted. Questions of physiological benefit
persist, and utilization is waning despite broader allocation policies that
encourage SPK, including consideration for patients with type 2 diabetes. The
purpose of this review will be to summarize the physiological data regarding
multiorgan transplantation and place these into context while reviewing current
allocation policy in the United States.
PMID- 27515043
TI - [Not Available].
PMID- 27515044
TI - [Not Available].
PMID- 27515045
TI - [Not Available].
PMID- 27515046
TI - Placental insufficiency among high-risk pregnancies with a normal umbilical
artery resistance index after 32weeks.
AB - OBJECTIVE: To determine the incidence of abnormal multi-vessel Doppler values
among advanced pregnancies at risk of suboptimal placentation but with a normal
umbilical artery resistance index (RI), and to assess whether clinical and
ultrasonography findings can identify them. METHODS: In a prospective cross
sectional study at Tygerberg Hospital, South Africa, women with high-risk
pregnancies but normal umbilical artery RI after 32weeks underwent
ultrasonography (fetal biometry, liquor, and placenta maturation) and Doppler
assessment (uterine, umbilical, and middle cerebral arteries) between February 11
and October 21, 2013. Study data were compared among four groups: fetuses with
normal uterofetoplacental Doppler values and those with any abnormal pulsatility
index, each subdivided into small for gestational age (SGA) and appropriate for
gestational age (AGA) by estimated fetal weight. RESULTS: Of 210 participants, 72
(36.2%) had abnormal Doppler results, and 60 (28.6%) fetuses were SGA (38 [63.3%]
with abnormal Doppler results). Clinical characteristics did not differ between
groups with normal or abnormal Doppler values; however, among normal Doppler
results, SGA pregnancies demonstrated poorer fundal growth (P=0.006). Significant
associations existed between abnormal Doppler results and asymmetric growth,
inappropriately advanced placental maturation, and reduced liquor volume (all
P<=0.04), but with very low sensitivities (3.9%, 4.8%, and 14.5%, respectively).
CONCLUSION: Maternal characteristics and imaging variables did not reliably
identify more than one-third of pregnancies with evidence of suboptimal
placentation.
PMID- 27515047
TI - Single oxygen vacancies of (TiO2)35 as a prototype reduced nanoparticle:
implication for photocatalytic activity.
AB - Titanium dioxide (TiO2), as a semiconductor metal oxide, has been one of the most
popular materials studied in the field of photocatalysis. In the present study,
the properties of single oxygen vacancies of (TiO2)35, a prototype of an anatase
nanoparticle, were investigated by DFT calculations. (TiO2)35 is the minimum
sized model (~2 nm) for a bipyramidal nanoparticle with anatase phase and eight
{101} facets. All the available oxygen vacancies at various sites according to
position, coordination number, and distance from the center atom were examined.
The geometric, energetic and electronic properties of the reduced TiO2 clusters
were analyzed by hybrid DFT functionals with different Hartree-Fock exchange
ratios (0, 12.5 and 25%). It was found that the structure of pristine (TiO2)35 is
somewhat different from the bulk lattice, with a relatively high surface to
volume ratio. Moreover, the particular highly (three)-coordinated oxygen atom is
energetically the most favorable for oxygen vacancy formation from the
nanoparticle mainly due to its substantially high relaxation energy. TiO2
nanoparticles have low oxygen vacancy formation energy and narrow band gap
because of their defect states, and can be utilized as an efficient photocatalyst
material.
PMID- 27515048
TI - Toll-like receptors: promising therapeutic targets for inflammatory diseases.
AB - The health of living organisms is constantly challenged by bacterial and viral
threats. The recognition of pathogenic microorganisms by diverse receptors
triggers a variety of host defense mechanisms, leading to their eradication. Toll
like receptors (TLRs), which are type I transmembrane proteins, recognize
specific signatures of the invading microbes and activate a cascade of downstream
signals inducing the secretion of inflammatory cytokines, chemokines, and type I
interferons. The TLR response not only counteracts the pathogens but also
initiates and shapes the adaptive immune response. Under normal conditions,
inflammation is downregulated after the removal of the pathogen and cellular
debris. However, a dysfunctional TLR-mediated response maintains a chronic
inflammatory state and leads to local and systemic deleterious effects in host
cells and tissues. Such inappropriate TLR response has been attributed to the
development and progression of multiple diseases such as cancer, autoimmune, and
inflammatory diseases. In this review, we discuss the emerging role of TLRs in
the pathogenesis of inflammatory diseases and how targeting of TLRs offers a
promising therapeutic strategy for the prevention and treatment of various
inflammatory diseases. Additionally, we highlight a number of TLR-targeting
agents that are in the developmental stage or in clinical trials.
PMID- 27515050
TI - Signal transducer and activator of transcription 3 as a therapeutic target for
cancer and the tumor microenvironment.
AB - Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic
transcription factor that modulates the transcription of a variety of genes to
regulate important biological functions, including cell proliferation,
differentiation, survival, angiogenesis, and immune response. Constitutive
activation of STAT3 is important in oncogenic signaling and occurs at high
frequency in human cancers, including diverse solid tumors and hematologic
malignancies. Moreover, it is associated with a poor prognosis. The tumor
microenvironment has recently been recognized as a key condition for cancer
progression, invasion, angiogenesis, metastasis, and drug resistance by
activation of STAT3 signaling. Therefore, understanding the biology associated
with STAT3-mediated signaling cascades in the tumor microenvironment may offer
the therapeutic potential to treat human cancers. This review presents an
overview of the critical roles of STAT3 in the tumor microenvironment related to
cancer biology and discusses recent advancements in the development of anticancer
drugs that therapeutically inhibit STAT3 signaling cascades.
PMID- 27515051
TI - Myofibroblasts and inflammatory cells as players of cardiac fibrosis.
AB - On myocardial infarction, many cells are injured or died owing to arterial
occlusion. Intracellular molecules released from injured or dead cells initiate
inflammatory responses that play important roles in cardiac remodeling including
fibrosis. Fibrosis is an excess accumulation of extracellular collagen.
Currently, drugs used to treat cardiac fibrosis are not commercially available.
Myofibroblasts are responsible for the production and secretion of collagen.
Infiltrating inflammatory cells interact with fibroblasts or other cells and
promote myofibroblast formation. Inflammatory cells also modulate the activities
of myofibroblasts. Regulation of collagen production is critical for modulating
the progression of fibrosis. Hence, the manipulation of activities of
inflammatory cells and myofibroblasts will provide promising therapeutic targets
for treatment of cardiac fibrosis.
PMID- 27515049
TI - Autophagy in the liver: cell's cannibalism and beyond.
AB - Chronic liver disease and its progression to liver failure are induced by various
etiologies including viral infection, alcoholic and nonalcoholic hepatosteatosis.
It is anticipated that the prevalence of fatty liver disease will continue to
rise due to the growing incidence of obesity and metabolic disorder. Evidence is
accumulating to indicate that the onset of fatty liver disease is causatively
linked to mitochondrial dysfunction and abnormal lipid accumulation. Current
treatment options for this disease are limited. Autophagy is an integral
catabolic pathway that maintains cellular homeostasis both selectively and
nonselectively. As mitophagy and lipophagy selectively remove dysfunctional
mitochondria and excess lipids, respectively, stimulation of autophagy could have
therapeutic potential to ameliorate liver function in steatotic patients. This
review highlights our up-to-date knowledge on mechanistic roles of autophagy in
the pathogenesis of fatty liver disease and its vulnerability to surgical stress,
with an emphasis on mitophagy and lipophagy.
PMID- 27515052
TI - Farnesoid X receptor as a regulator of fuel consumption and mitochondrial
function.
AB - Maintenance of energy homeostasis is crucial for survival of organism. There
exists a close link between energy metabolism and cell survival, which are
coordinately regulated by common signaling pathways. Farnesoid X receptor (FXR)
serves as a ligand-mediated transcription factor to regulate diverse genes
involved in bile acid, lipid, and glucose metabolism, controlling cellular and
systemic energy metabolism. Another important aspect on FXR biology is related to
its beneficial effect on cell survival. FXR exerts antioxidative and
cytoprotective effect, which is closely associated with the ability of FXR to
regulate mitochondrial function. To maintain complex biological processes under
homeostasis, FXR activity needs to be dynamically and tightly controlled by
different signaling pathways and modifications. In this review, we discuss the
role of FXR in the regulation of energy metabolism and cell survival, with the
goal of understanding molecular basis for FXR regulation in physiological and
pathological conditions. This information may be of assistance in understanding
recent advancements of FXR research and strategies for the prevention and
treatment of metabolic disorders.
PMID- 27515053
TI - Activin A secreted by human mesenchymal stem cells induces neuronal development
and neurite outgrowth in an in vitro model of Alzheimer's disease: neurogenesis
induced by MSCs via activin A.
AB - Alzheimer's disease (AD) is characterized by progressive loss of memory in
addition to cortical atrophy. Cortical atrophy in AD brains begins in the
parietal and temporal lobes, which are near the subventricular zone (SVZ). The
aim of this study was to activate the neurogenesis in the SVZ of AD brains by
human mesenchymal stem cells (hMSCs). Neural stem cells (NSCs) were isolated from
SVZ of 4-month-old 5XFAD mice. Co-culture of hMSCs with SVZ-derived NSCs from
5XFAD mice induced neuronal development and neurite outgrowth. To examine the
inducing factor of neurogenesis, human cytokine array was performed with co
cultured media, and revealed elevated release of activin A from hMSCs. Also, we
confirmed that the mRNA levels of activin A and activin receptor in the SVZ of
5XFAD mice were significantly lower than normal mice. Treatment of human
recombinant activin A in SVZ-derived NSCs from 5XFAD mice induced neuronal
development and neurite outgrowth. These data suggest that use of hMSCs and
activin A to recover neurogenesis in future studies of cortical regeneration to
treat AD.
PMID- 27515054
TI - A novel mechanism for the pyruvate protection against zinc-induced cytotoxicity:
mediation by the chelating effect of citrate and isocitrate.
AB - Intracellular accumulation of free zinc contributes to neuronal death in brain
injuries such as ischemia and epilepsy. Pyruvate, a glucose metabolite, has been
shown to block zinc neurotoxicity. However, it is largely unknown how pyruvate
shows such a selective and remarkable protective effect. In this study, we sought
to find a plausible mechanism of pyruvate protection against zinc toxicity.
Pyruvate almost completely blocked cortical neuronal death induced by zinc, yet
showed no protective effects against death induced by calcium (ionomycin, NMDA)
or ferrous iron. Of the TCA cycle intermediates, citrate, isocitrate, and to a
lesser extent oxaloacetate, protected against zinc toxicity. We then noted with
LC-MS/MS assay that exposure to pyruvate, and to a lesser degree oxaloacetate,
increased levels of citrate and isocitrate, which are known zinc chelators. While
pyruvate added only during zinc exposure did not reduce zinc toxicity, citrate
and isocitrate added only during zinc exposure, as did extracellular zinc
chelator CaEDTA, completely blocked it. Furthermore, addition of pyruvate after
zinc exposure substantially reduced intracellular zinc levels. Our results
suggest that the remarkable protective effect of pyruvate against zinc
cytotoxicity may be mediated indirectly by the accumulation of intracellular
citrate and isocitrate, which act as intracellular zinc chelators.
PMID- 27515055
TI - Attenuation of Abeta toxicity by promotion of mitochondrial fusion in
neuroblastoma cells by liquiritigenin.
AB - Mitochondrial dynamics control mitochondrial morphology and function, and
aberrations in these are associated with various neurodegenerative diseases
including Alzheimer's disease and Parkinson's disease. To identify novel
regulators of mitochondrial dynamics, we screened a phytochemical library and
identified liquiritigenin as a potent inducer of mitochondrial fusion. Treatment
with liquiritigenin induced an elongated mitochondrial morphology in SK-N-MC
cells. In addition, liquiritigenin rescued mitochondrial fragmentation induced by
knockout of mitochondrial fusion mediators such as Mfn1, Mfn2, and Opa1.
Furthermore, we found that treatment with liquiritigenin notably inhibited
mitochondrial fragmentation and cytotoxicity induced by Abeta in SK-N-MC cells.
PMID- 27515056
TI - The confusion continues: results from an American Association for the Surgery of
Trauma survey on massive transfusion practices among United States trauma
centers.
AB - BACKGROUND: Massive transfusion practices have undergone several recent
developments. We sought to examine institutional practices guiding hemostatic
resuscitation in the setting of massive hemorrhage. STUDY DESIGN AND METHODS: A
37-question online survey was sent to American Association for the Surgery of
Trauma members. RESULTS: A total of 191 surgeons from 125 institutions completed
the survey. Level I and II centers composed 70 and 18% of responding sites,
respectively. A total of 123 institutions have a massive transfusion protocol
(MTP); 54% report having an MTP for less than 5 years. The number of coolers and
units of red blood cells, plasma, and platelets are highly variable. Tranexamic
acid is part of the MTP at 64% of centers; 26% continue to use recombinant
activated Factor VII. MTP activation occurs more than five times per month at 32%
of centers. MTPs are utilized for nontrauma patients in 82% of institutions.
Point-of-care prothrombin time, international normalized ratio, and partial
thromboplastin time testing is utilized in 37% of institutions. Only 9% routinely
utilize thromboelastography or rotational thromboelastometry (TEG/ROTEM) within
their MTP. Just 7% use a validated scoring system to guide MTP activation. The
incorporation of TEG/ROTEM into the MTP is associated with the use of a scoring
system in regression analysis (p = 0.024). CONCLUSION: Most institutions
regularly activate recently implemented MTPs for trauma and nontrauma
indications; however, few use validated scoring systems for MTP activation. MTP
content is highly variable. Few institutions use TEG, while most have
incorporated tranexamic acid into their protocol. The lack of consistent
practices underscores the need for outcome-based studies to guide transfusion
practices.
PMID- 27515058
TI - Position 97 of HLA-B, a residue implicated in pathogenesis of ankylosing
spondylitis, plays a key role in cell surface free heavy chain expression.
AB - OBJECTIVE: Association of position 97 (P97) residue polymorphisms in human
leucocyte antigen (HLA)-B, including HLA-B*27, with ankylosing spondylitis (AS)
has recently been reported. We studied the effect of P97 variations on cell
surface expression of the AS-associated HLA-B*27 and HLA-B*51, and the AS
protective HLA-B*7. METHODS: Flow cytometry was used to measure surface
expression of HLA-B*27 in C1R/HeLa cells expressing HLA-B*27 (N97) and six
mutants at P97 (N97T, N97S, N97V, N97R, N97W and N97D). Transporter associated
with antigen processing-deficient T2, tapasin-deficient 220, beta2m-deficient
HCT15 and endoplasmic reticulum aminopeptidase 1 or beta2m-clustered regularly
interspaced short palindromic repeats/Cas9-knockout HeLa cells were used to
provide evidence for specific protein interactions. Surface expression of HLA
B*7/HLA-B*51 P97 mutants was also studied. RESULTS: Mutation of HLA-B*27 P97 to
the AS risk residue threonine increased cell surface free heavy chain (FHC)
expression. Protective residues (serine or valine) and non-AS-associated residues
(arginine or tryptophan) did not alter FHC expression. The N97D mutation reduced
expression of conventional and FHC forms of HLA-B*27. Differences in FHC
expression levels between HLA-B*27, HLA-B*27-N97T and HLA-B*27-N97D were
dependent on the presence of functional beta2m. HLA-B*7, which has an AS
protective serine at P97, expressed lower levels of FHC than HLA-B*27 or HLA
B*51. Introduction of asparagine at P97 of both HLA-B*7 and HLA-B*51 increased
FHC expression. CONCLUSIONS: The nature of P97 residue affects surface expression
of HLA-B*27, B*7 and B*51, with AS-associated residues giving rise to higher FHC
expression levels. The association of P97 amino acid polymorphisms with AS could
be, at least in part, explained by its effect on HLA-B*27 FHC cell surface
expression.
PMID- 27515059
TI - Child height gain is associated with consumption of animal-source foods in
livestock-owning households in Western Kenya.
AB - OBJECTIVE: To clarify the pathways between household livestock and child growth
by assessing the relationships between consumption of animal-source foods (ASF)
and child growth and evaluating the household livestock correlates of child
consumption of ASF. DESIGN: We conducted a longitudinal cohort study of
anthropometry and 3 d feeding recalls among children <5 years old between June
2014 and May 2015. In addition, we collected data on wealth, livestock ownership
and livestock diseases in the same households. We used linear and negative
binomial mixed models to evaluate the relationships between household livestock
characteristics, reported consumption of ASF and child growth. SETTING: An 1800
household surveillance catchment area in Western Kenya within the structure of
human and animal health surveillance systems. SUBJECTS: Children (n 874) <5 years
old. RESULTS: Among children >6 months old, reported frequency of egg and milk
consumption was associated with increased monthly height gain (for each
additional report of consumption over 3 d: adjusted beta (95 % CI)=0.010 (0.002,
0.019) cm/month and 0.008 (0.004, 0.013) cm/month, respectively). Poultry
ownership was associated with higher reported frequency of egg, milk and chicken
consumption (adjusted incidence rate ratio (95 % CI)=1.3 (1.2, 1.4), 1.4 (1.1,
1.6) and 1.3 (1.1, 1.4), respectively). Some livestock diseases were associated
with lower reported frequency of ASF intake (livestock digestive diseases
adjusted incidence rate ratio (95 % CI)=0.89 (0.78, 1.00)). CONCLUSIONS: Child
height gain was associated with milk and egg consumption in this cohort. ASF
consumption was related to both household livestock ownership and animal health.
PMID- 27515057
TI - Consensus-based recommendations for the management of juvenile dermatomyositis.
AB - BACKGROUND: In 2012, a European initiative called Single Hub and Access point for
pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate
diagnostic and management regimens in Europe for children and young adults with
rheumatic diseases. Juvenile dermatomyositis (JDM) is a rare disease within the
group of paediatric rheumatic diseases (PRDs) and can lead to significant
morbidity. Evidence-based guidelines are sparse and management is mostly based on
physicians' experience. Consequently, treatment regimens differ throughout
Europe. OBJECTIVES: To provide recommendations for diagnosis and treatment of
JDM. METHODS: Recommendations were developed by an evidence-informed consensus
process using the European League Against Rheumatism standard operating
procedures. A committee was constituted, consisting of 19 experienced paediatric
rheumatologists and 2 experts in paediatric exercise physiology and physical
therapy, mainly from Europe. Recommendations derived from a validated systematic
literature review were evaluated by an online survey and subsequently discussed
at two consensus meetings using nominal group technique. Recommendations were
accepted if >80% agreement was reached. RESULTS: In total, 7 overarching
principles, 33 recommendations on diagnosis and 19 recommendations on therapy
were accepted with >80% agreement among experts. Topics covered include
assessment of skin, muscle and major organ involvement and suggested treatment
pathways. CONCLUSIONS: The SHARE initiative aims to identify best practices for
treatment of patients suffering from PRD. Within this remit, recommendations for
the diagnosis and treatment of JDM have been formulated by an evidence-informed
consensus process to produce a standard of care for patients with JDM throughout
Europe.
PMID- 27515061
TI - Asymptomatic Bilateral Internal Carotid Artery Aneurysms with Distal High-grade
Stenosis in a Patient with Type 1 Neurofibromatosis.
PMID- 27515060
TI - Endometrial sampling devices for early diagnosis of endometrial lesions.
AB - PURPOSE: Endometrial carcinoma is the most common gynecologic malignancy in both
developed and some developing countries. Unlike cervical cancer, for which there
is routine screening, only patients symptomatic for endometrial carcinoma
typically seek medical help for its diagnosis and treatment. Dilatation and
curettage (D&C) has been the standard procedure for evaluating suspicious
endometrial lesions. The discomfort and injury caused by the D&C procedure,
however, restrict its use as a screening method for early diagnosis of
endometrial lesions. High-risk endometrial cancer patients would benefit from an
effective and low-cost screening test. In recent years, several endometrial
devices have been developed and proposed as screening tools. METHODS: We have
reviewed and evaluated the literature relating to the endometrial sampling
devices in clinical use or clinical trials, with the goal of comparing devices
and identifying the most appropriate ones for screening for endometrial lesions.
Eligible literature was identified from systematic PubMed searches, and the
relevant data were extracted. Comments, letters, unpublished data, conference
proceedings, and case reports were excluded from our search. Seventy-four
articles on endometrial sampling devices were obtained for this review. RESULTS:
The main screening devices for endometrial carcinoma are aspiration devices (such
as the Vabra aspirator), Pipelle, Tao Brush, and SAP-1 device. Among these
devices, the Tao Brush is the most promising endometrial sampler for screening
for endometrial lesions. However, its sampling insufficiency, cost, and
unsuccessful insertion rate (20 % in nulliparous and 8 % in parous women) are
problematic. CONCLUSIONS: A more accurate and low-cost endometrial sampler, with
improved specimen sufficiency and higher sensitivity for endometrial lesions,
needs tobe developed and clinically verified.
PMID- 27515062
TI - Vasa Nervorum as the Source of Corkscrew Collaterals in Thromboangiitis
Obliterans (Buerger's Disease).
PMID- 27515063
TI - How patients think about social responsibility of public hospitals in China?
AB - BACKGROUND: Hospital social responsibility is receiving increasing attention,
especially in China where major changes to the healthcare system have taken
place. This study examines how patients viewed hospital social responsibility in
China and explore the factors that influenced patients' perception of hospital
social responsibility. METHODS: A cross-sectional survey was conducted, using a
structured questionnaire, on a sample of 5385 patients from 48 public hospitals
in three regions of China: Shanghai, Hainan, and Shaanxi. A multilevel regression
model was employed to examine factors influencing patients' assessments of
hospital social responsibility. Intra-class correlation coefficients (ICCs) were
calculated to estimate the proportion of variance in the dependent variables
determined at the hospital level. RESULTS: The scores for service quality,
appropriateness, accessibility and professional ethics were positively associated
with patients' assessments of hospital social responsibility. Older outpatients
tended to give lower assessments, while inpatients in larger hospitals scored
higher. After adjusted for the independent variables, the ICC rose from 0.182 to
0.313 for inpatients and from 0.162 to 0.263 for outpatients. The variance at the
patient level was reduced by 51.5 and 48.6 %, respectively, for inpatients and
outpatients. And the variance at the hospital level was reduced by 16.7 % for
both groups. CONCLUSIONS: Some hospital and patient characteristics and their
perceptions of service quality, appropriateness, accessibility and professional
ethics were associated with their assessments of public hospital social
responsibility. The differences were mainly determined at the patient level. More
attention to law-abiding behaviors, cost-effective health services, and
charitable works could improve perceptions of hospitals' adherence to social
responsibility.
PMID- 27515064
TI - A Novel Perspective on the Biology of Bilirubin in Health and Disease.
AB - Unconjugated bilirubin (UCB) is known to be one of the most potent endogenous
antioxidant substances. While hyperbilirubinemia has long been recognized as an
ominous sign of liver dysfunction, recent data strongly indicate that mildly
elevated bilirubin (BLB) levels can be protective against an array of diseases
associated with increased oxidative stress. These clinical observations are
supported by new discoveries relating to the role of BLB in immunosuppression and
inhibition of protein phosphorylation, resulting in the modulation of
intracellular signaling pathways in vascular biology and cancer, among others.
Collectively, the evidence suggests that targeting BLB metabolism could be
considered a potential therapeutic approach to ameliorate a variety of
conditions.
PMID- 27515065
TI - Ivo Pitanguy.
PMID- 27515066
TI - Erythrocytes do not activate purified and platelet soluble guanylate cyclases
even in conditions favourable for NO synthesis.
AB - BACKGROUND: Direct interaction between Red blood cells (RBCs) and platelets is
known for a long time. The bleeding time is prolonged in anemic patients
independent of their platelet count and could be corrected by transfusion of
RBCs, which indicates that RBCs play an important role in hemostasis and platelet
activation. However, in the last few years, opposing mechanisms of platelet
inhibition by RBCs derived nitric oxide (NO) were proposed. The aim of our study
was to identify whether RBCs could produce NO and activate soluble guanylate
cyclase (sGC) in platelets. METHODS: To test whether RBCs could activate sGC
under different conditions (whole blood, under hypoxia, or even loaded with NO),
we used our well-established and highly sensitive models of NO-dependent sGC
activation in platelets and activation of purified sGC. The activation of sGC was
monitored by detecting the phosphorylation of Vasodilator Stimulated
Phosphoprotein (VASP(S239)) by flow cytometry and Western blot. ANOVA followed by
Bonferroni's test and Student's t-test were used as appropriate. RESULTS: We show
that in the whole blood, RBCs prevent NO-mediated inhibition of ADP and TRAP6
induced platelet activation. Likewise, coincubation of RBCs with platelets
results in strong inhibition of NO-induced sGC activation. Under hypoxic
conditions, incubation of RBCs with NO donor leads to Hb-NO formation which
inhibits sGC activation in platelets. Similarly, RBCs inhibit activation of
purified sGC, even under conditions optimal for RBC-mediated generation of NO
from nitrite. CONCLUSIONS: All our experiments demonstrate that RBCs act as
strong NO scavengers and prevent NO-mediated inhibition of activated platelets.
In all tested conditions, RBCs were not able to activate platelet or purified
sGC.
PMID- 27515067
TI - First Comprehensive Proteome Analyses of Lysine Acetylation and Succinylation in
Seedling Leaves of Brachypodium distachyon L.
AB - Protein acetylation and succinylation are the most crucial protein post
translational modifications (PTMs) involved in the regulation of plant growth and
development. In this study, we present the first lysine-acetylation and lysine
succinylation proteome analysis of seedling leaves in Brachypodium distachyon L
(Bd). Using high accuracy nano LC-MS/MS combined with affinity purification, we
identified a total of 636 lysine-acetylated sites in 353 proteins and 605 lysine
succinylated sites in 262 proteins. These proteins participated in many biology
processes, with various molecular functions. In particular, 119 proteins and 115
sites were found to be both acetylated and succinylated, simultaneously. Among
the 353 acetylated proteins, 148 had acetylation orthologs in Oryza sativa L.,
Arabidopsis thaliana, Synechocystis sp. PCC 6803, and Glycine max L. Among the
262 succinylated proteins, 170 of them were found to have homologous proteins in
Oryza sativa L., Escherichia coli, Sacchayromyces cerevisiae, or Homo sapiens.
Motif-X analysis of the acetylated and succinylated sites identified two new
acetylated motifs (K---K and K-I-K) and twelve significantly enriched
succinylated motifs for the first time, which could serve as possible binding
loci for future studies in plants. Our comprehensive dataset provides a promising
starting point for further functional analysis of acetylation and succinylation
in Bd and other plant species.
PMID- 27515068
TI - Supramolecular Metallo-Bioadhesive for Minimally Invasive Use.
AB - A novel metallo-bioadhesive to be used as tissue sealant in minimally invasive
procedures is reported. Metal complexation can be used to render gelatin
derivatives adhesive, which occurs in minutes, is efficient, and fully
biodegradable within weeks.
PMID- 27515069
TI - Development and validation of a simple risk score to predict 30-day readmission
after percutaneous coronary intervention in a cohort of medicare patients.
AB - OBJECTIVES: To develop a risk model that can be used to identify PCI patients at
higher risk of readmission who may benefit from additional resources at the time
of discharge. BACKGROUND: A high proportion of patients undergoing PCI are
readmitted within 30 days of discharge. METHODS: The sample comprised patients
aged >=65 years who underwent PCI at a CathPCI Registry(r)-participating hospital
and could be linked with 100% Medicare fee-for-service claims between 01/2007 and
12/2009. The sample (n = 388,078) was randomly divided into risk score
development (n = 193,899) and validation (n = 194,179) cohorts. We did not count
as readmissions those associated with staged revascularization procedures.
Multivariable logistic regression models using stepwise selection models were
estimated to identify variables independently associated with all-cause 30-day
readmission. RESULTS: The mean 30-day readmission rates for the development
(11.36%) and validation (11.35%) cohorts were similar. In total, 19 variables
were significantly associated with risk of 30-day readmission (P < 0.05), and
model c-statistics were similar in the development (0.67) and validation (0.66)
cohorts. The simple risk score based on 14 variables identified patients at high
and low risk of readmission. Patients with a score of >=13 (15.4% of sample) had
more than an 18.5% risk of readmission, while patients with a score <=6 (41.9% of
sample) had less than an 8% risk of readmission. CONCLUSION: Among PCI patients,
risk of readmission can be estimated using clinical factors present at the time
of the procedure. This risk score may guide clinical decision-making and resource
allocation for PCI patients at the time of hospital discharge. (c) 2016 Wiley
Periodicals, Inc.
PMID- 27515070
TI - Quality of life and patient benefit following transition from methotrexate to
ustekinumab in psoriasis.
AB - BACKGROUND: TRANSIT (NCT01059773) compared immediate and gradual transition from
methotrexate to ustekinumab in psoriasis patients via multiple measures,
including patient-reported outcomes. OBJECTIVE: To evaluate patient perception of
treatment benefits in TRANSIT. METHODS: A total of 489 psoriasis patients
received ustekinumab, with immediate cessation of methotrexate (Arm 1) or 4
weeks' overlap with decreasing methotrexate dose (Arm 2). Ustekinumab was
administered at weeks 0, 4, 16, 28 and 40. Dermatology Life Quality Index (DLQI),
EuroQol 5-item (EQ-5D), visual analogue scale (VAS) valuation technique and
patient benefit index (PBI) were employed. Mean global PBI and sub-scores were
calculated from the sum of the benefit items weighted by their respective
relevance at baseline. Patient-relevant benefit was defined as PBI >=1 (scale: 0
[no benefit] to 4 [maximum benefit]). Correlations of global PBI with Psoriasis
Area and Severity Index (PASI) and DLQI were examined. RESULTS: Relationships
between PBI and clinical data were evaluable in 340 patients. The most important
treatment goals at baseline included: 'be healed of all skin defects', 'have
confidence in therapy', 'get better skin quickly' and 'regain control of the
disease'. Benefit in PBI global score was achieved at week 4 by 93% of patients
in Arm 1 and 91% in Arm 2. Global PBI scores increased in both Arms between weeks
4 and 52. Global PBI correlated weakly with PASI change from baseline
(correlation coefficient range: -0.22 to -0.40), and moderately with DLQI (-0.29
to -0.54). Overall DLQI score was lower than baseline at all times; and the
percentage of patients with an overall score of 0 or 1 increased with time.
Correspondingly, EQ VAS scores increased with time. DLQI and EQ VAS results were
similar between arms. CONCLUSIONS: Regardless of the strategy for transitioning
from methotrexate, ustekinumab was associated with rapid and sustained
improvement in patient-reported outcomes. PBI appears a suitable tool for
assessing patient-relevant treatment benefits in psoriasis patients.
PMID- 27515071
TI - Expression of Epitope-Tagged Proteins in Mammalian Cells in Culture.
AB - Before the advent of molecular methods to tag proteins, visualization of proteins
within cells required the use of antibodies directed against the protein of
interest. Thus, only proteins for which antibodies were available could be
visualized. Epitope tagging allows the detection of all proteins with existing
sequence information, irrespective of the availability of antibodies directed
against them. This technique involves the generation of DNA constructs that
express the protein of interest tagged with an epitope that can be recognized by
a commercially available antibody. Proteins can be tagged with a wide variety of
epitopes using commercially available vectors that allow expression in mammalian
cells. Epitope-tagged proteins are easily transfected into mammalian cell lines
and, in most cases, tightly mimic the behavior of the endogenous protein. Tagged
proteins exogenously expressed in cells provide different types of information
depending on the subsequent detection approaches. Using immunofluorescence and
immunoelectron microscopy with anti-tag antibodies, relative to known markers of
cellular organelles, can provide information on the subcellular localization of
the tagged protein and may provide clues regarding the protein's function.
Immunofluorescence with anti-tag antibodies can also be utilized to assess the
tagged protein's responses to cellular signals and pharmacological treatments.
Immunoprecipitations with anti-tag antibodies can recover protein complexes
containing the protein of interest, resulting in the identification of
interacting proteins. Recovery of tagged proteins on affinity matrices allows
their purification for use in biochemical assays. In addition, specialized
fluorescent tags, such as the green fluorescent protein (GFP) allow the analysis
of cellular dynamics in live cells in real time.
PMID- 27515072
TI - Antibody Production with Synthetic Peptides.
AB - Peptides (usually 10-20 amino acid residues in length) can be used as effectively
as proteins in raising antibodies producing both polyclonal and monoclonal
antibodies routinely with titers higher than 20,000. Peptide antigens do not
function as immunogens unless they are conjugated to proteins. Production of high
quality antipeptide antibodies is dependent upon peptide sequence selection, the
success of peptide synthesis, peptide-carrier protein conjugation, the humoral
immune response in the host animal, the adjuvant used, the peptide dose
administered, the injection method, and the purification of the antibody. Peptide
sequence selection is probably the most critical step in the production of
antipeptide antibodies. Although the process for designing peptide antigens is
not exact, several guidelines and computational B-cell epitope prediction methods
can help maximize the likelihood of producing antipeptide antibodies that
recognize the protein. Antibodies raised by peptides have become essential tools
in life science research. Virtually all phospho-specific antibodies are now
produced using phosphopeptides as antigens. Typically, 5-20 mg of peptide is
enough for antipeptide antibody production. It takes 3 months to produce a
polyclonal antipeptide antibody in rabbits that yields ~100 mL of serum which
corresponds to ~8-10 mg of the specific antibody after affinity purification
using a peptide column.
PMID- 27515073
TI - Production and Purification of Polyclonal Antibodies.
AB - Polyclonal antibodies consist of a mixture of antibodies produced by multiple B
cell clones that have differentiated into antibody-producing plasma cells in
response to an immunogen. Polyclonal antibodies raised against an antigen
recognize multiple epitopes on a target molecule, which results in a signal
amplification in indirect immunoassays including immune-electron microscopy. In
this chapter, we present a basic procedure to generate polyclonal antibodies in
rabbits.
PMID- 27515074
TI - Preparation of Colloidal Gold Particles and Conjugation to Protein A/G/L, IgG,
F(ab')2, and Streptavidin.
AB - Colloidal gold probes, including protein A/G/L, IgG, F(ab')2, and streptavidin
labeled with gold particles, are useful tools to localize antigens in cells and
tissues by immunoelectron microscopy (IEM). This chapter describes different
methods for the preparation of colloidal gold and conjugation of colloidal gold
to protein A/G/L, IgG, and streptavidin.
PMID- 27515075
TI - Helper-Dependent Adenoviral Vectors and Their Use for Neuroscience Applications.
AB - Neuroscience research has been revolutionized by the use of recombinant viral
vector technology from the basic, preclinical and clinical levels. Currently,
multiple recombinant viral vector types are employed with each having its
strengths and weaknesses depending on the proposed application. Helper-dependent
adenoviral vectors (HdAd) are emerging as ideal viral vectors that solve a major
need in the neuroscience field: (1) expression of transgenes that are too large
to be packaged by other viral vectors and (2) rapid onset of transgene expression
in the absence of cytotoxicity. Here, we describe the methods for large-scale
production of HdAd viral vectors for in vivo use with neurospecific transgene
expression.
PMID- 27515076
TI - Localizing Proteins in Fixed Giardia lamblia and Live Cultured Mammalian Cells by
Confocal Fluorescence Microscopy.
AB - Confocal fluorescence microscopy and electron microscopy (EM) are complementary
methods for studying the intracellular localization of proteins. Confocal
fluorescence microscopy provides a rapid and technically simple method to
identify the organelle in which a protein localizes but only EM can identify the
suborganellular compartment in which that protein is present. Confocal
fluorescence microscopy, however, can provide information not obtainable by EM
but required to understand the dynamics and interactions of specific proteins. In
addition, confocal fluorescence microscopy of cells transfected with a construct
encoding a protein of interest fused to a fluorescent protein tag allows live
cell studies of the subcellular localization of that protein and the monitoring
in real time of its trafficking. Immunostaining methods for confocal fluorescence
microscopy are also faster and less involved than those for EM allowing rapid
optimization of the antibody dilution needed and a determination of whether
protein antigenicity is maintained under fixation conditions used for EM
immunogold labeling. This chapter details a method to determine by confocal
fluorescence microscopy the intracellular localization of a protein by
transfecting the organism of interest, in this case Giardia lamblia, with the
cDNA encoding the protein of interest and then processing these organisms for
double label immunofluorescence staining after chemical fixation. Also presented
is a method to identify the organelle targeting information in the presequence of
a precursor protein, in this case the presequence of the precursor to the Euglena
light harvesting chlorophyll a/b binding protein of photosystem II precursor
(pLHCPII), using live cell imaging of mammalian COS7 cells transiently
transfected with a plasmid encoding a pLHCPII presequence fluorescent protein
fusion and stained with organelle-specific fluorescent dyes.
PMID- 27515077
TI - Using Fluorescent Protein Fusions to Study Protein Subcellular Localization and
Dynamics in Plant Cells.
AB - Studies of protein subcellular localization and dynamics are helpful in
understanding the cellular functions of proteins in an organism. In the past
decade, the use of green fluorescent protein (GFP) as a fusion tag has
dramatically extended our knowledge in this field. Transient expression and
stable transformation of GFP-tagged proteins have been wildly used to study
protein localization in vivo in different systems. Although GFP-based tags
provide a fast and convenient way to characterize protein properties in living
cells, several reports have demonstrated that GFP fusions might not accurately
reflect the localization of the native protein as GFP tags may alter the protein
properties. To facilitate proper usage of GFP tags in plant cell biology study,
we describe detailed protocols to identify possible inhibitory effects of
fluorescent tags on protein subcellular localization and to determine if a
fluorescently tagged protein is localized to the correct subcellular compartment.
Using Arabidopsis Endomembrane protein 12 (EMP12) as an example, we first show
the possible inhibitory effect of GFP tags on proper protein localization and
then describe the immunofluorescence labeling method to verify the correct
localization of GFP fusion proteins. Next, a method is presented using the ImageJ
program with the Pearson-Spearman correlation (PSC) colocalization plug-in for
statistical quantification of colocalization ratios of two fluorophores. Finally
we provide a detailed method for protein dynamics studies using spinning disk
confocal microscopy in Arabidopsis cells.
PMID- 27515078
TI - Using FRAP or FRAPA to Visualize the Movement of Fluorescently Labeled Proteins
or Cellular Organelles in Live Cultured Neurons Transformed with Adeno-Associated
Viruses.
AB - Fluorescence recovery after photobleaching (FRAP) and fluorescence redistribution
after photoactivation (FRAPA) are complementary methods used to gauge the
movement of proteins or sub-resolution organelles within cells. Using these
methods we can determine the nature of the movement of labeled particles, whether
it is random, constrained, or active, the coefficient of diffusion if applicable,
binding and unbinding constants, and the direction of active transport. These two
techniques have been extensively utilized to probe the cell biology of neurons. A
practical outline of FRAP and FRAPA in cultured neurons is presented, including
the preparation of the neurons and their infection with adeno-associated viral
vectors. Considerations in planning such experiments are provided.
PMID- 27515079
TI - Bimolecular Fluorescence Complementation (BiFC) Analysis of Protein-Protein
Interactions and Assessment of Subcellular Localization in Live Cells.
AB - Bimolecular fluorescence complementation (BiFC) is a fluorescence imaging
technique used to visualize protein-protein interactions (PPIs) in live cells and
animals. One unique application of BiFC is to reveal subcellular localization of
PPIs. The superior signal-to-noise ratio of BiFC in comparison with fluorescence
resonance energy transfer or bioluminescence resonance energy transfer enables
its wide applications. Here, we describe how confocal microscopy can be used to
detect and quantify PPIs and their subcellular localization. We use basic leucine
zipper transcription factor proteins as an example to provide a step-by-step BiFC
protocol using a Nikon A1 confocal microscope and NIS-Elements imaging software.
The protocol given below can be readily adapted for use with other confocal
microscopes or imaging software.
PMID- 27515080
TI - Viral Injection and Cranial Window Implantation for In Vivo Two-Photon Imaging.
AB - Two-photon (2P) imaging has proven to be a powerful tool for investigating neural
structure and function both in brain slices and in intact systems. In vivo 2P
imaging presents significant challenges in sample preparation, which are
exacerbated in non-murine species. Here, we describe procedures for the effective
virally mediated labeling of neurons and for the implantation of cranial windows
for imaging. The procedures described here are applicable to a range of species,
including mice, and are routinely used in ferrets and tree shrews to provide
large-scale labeling of cortical volumes and high-quality imaging data.
PMID- 27515081
TI - Imaging Synaptic Vesicle Exocytosis-Endocytosis with pH-Sensitive Fluorescent
Proteins.
AB - The introduction of pHluorin, a pH-sensitive GFP, by Miesenbock and colleagues
provided a versatile tool to studies of vesicle trafficking, in particular
synaptic vesicle exocytosis and endocytosis. By tagging pHluorin to the luminal
region of the synaptic vesicular protein synaptobrevin (also called VAMP, vesicle
associated membrane protein) or other synaptic vesicle-specific proteins such as
the vesicular glutamate transporter-1, we are able to directly track synaptic
vesicle endocytosis in response to stimuli in a molecularly specific manner.
Here, we describe the process of imaging synaptic vesicle endocytosis in response
to extracellular stimulation in dissociated neuronal cultures of hippocampal
neurons obtained from rats-also applicable to mice-using pHluorin-tagged
vesicular glutamate transporter-1 as a reporter.
PMID- 27515082
TI - Immunogold Protein Localization on Grid-Glued Freeze-Fracture Replicas.
AB - Immunogold labeling of freeze-fracture replicas has recently been used for high
resolution visualization of protein localization in electron microscopy. This
method has higher labeling efficiency than conventional immunogold methods for
membrane molecules allowing precise quantitative measurements. However, one of
the limitations of freeze-fracture replica immunolabeling is difficulty in
keeping structural orientation and identifying labeled profiles in complex
tissues like brain. The difficulty is partly due to fragmentation of freeze
fracture replica preparations during labeling procedures and limited
morphological clues on the replica surface. To overcome these issues, we
introduce here a grid-glued replica method combined with SEM observation. This
method allows histological staining before dissolving the tissue and easy
handling of replicas during immunogold labeling, and keeps the whole replica
surface intact without fragmentation. The procedure described here is also useful
for matched double-replica analysis allowing further identification of labeled
profiles in corresponding P-face and E-face.
PMID- 27515083
TI - Pre-embedding Double-Label Immunoelectron Microscopy of Chemically Fixed Tissue
Culture Cells.
AB - Localization of specific proteins within cells at the nanometer level of
resolution is central to understanding how these proteins function in cell
processes such as motility and intracellular trafficking. Such localization can
be achieved by combining transmission electron microscopy (TEM) with immunogold
labeling. Here we describe a pre-embedding, indirect gold immunolabeling approach
to localize two different proteins of interest with secondary antibodies labeled
with gold particles of different sizes in cells grown on cover slips. In this
protocol, the cells are immunolabeled prior to being embedded in an epoxy resin
for ultrathin sectioning. The protocol also includes strategies for optimizing
the balance between ultrastructure and antigen preservation, steps to minimize
nonspecific antibody binding, and steps to optimize antibody penetration.
PMID- 27515084
TI - Immunoelectron Microscopy of Cryofixed and Freeze-Substituted Plant Tissues.
AB - Cryofixation and freeze-substitution techniques provide excellent preservation of
plant ultrastructure. The advantage of cryofixation is not only in structural
preservation, as seen in the smooth plasma membrane, but also in the speed in
arresting cell activity. Immunoelectron microscopy reveals the subcellular
localization of molecules within cells. Immunolabeling in combination with
cryofixation and freeze-substitution techniques provides more detailed
information on the immunoelectron-microscopic localization of molecules in the
plant cell than can be obtained from chemically fixed tissues. Here, we introduce
methods for immunoelectron microscopy of cryofixed and freeze-substituted plant
tissues.
PMID- 27515085
TI - Immunoelectron Microscopy of Cryofixed Freeze-Substituted Yeast Saccharomyces
cerevisiae.
AB - Immunolabeling electron microscopy is a challenging technique with demands for
perfect ultrastructural and antigen preservation. High-pressure freezing offers
an excellent way to fix cellular structure. However, its use for immunolabeling
has remained limited because of the low frequency of labeling due to loss of
protein antigenicity or accessibility. Here we present a protocol for immunogold
labeling of the yeast Saccharomyces cerevisiae that gives specific and multiple
labeling while keeping the finest structural details. We use the protocol to
reveal the organization of individual nuclear pore complex proteins and the
position of transport factors in the yeast Saccharomyces cerevisiae in relation
to actual transport events.
PMID- 27515086
TI - Pre-embedding Method of Electron Microscopy for Glycan Localization in Mammalian
Tissues and Cells Using Lectin Probes.
AB - In recent years, the study of glycans is progressing remarkably by the
development of glycan analysis systems using mass spectrometry, glycan profiling
systems using lectin microarrays, and glycoprotein analysis by the isotope-coded
glycosylation site-specific tagging method. With these methodologies, glycan
structures and biological functions are being elucidated. In the study of glycan
function as well as disease diagnosis, it is important to examine the
localization of glycans in tissues and cells. Histochemical methods using lectin
probes can localize glycans in the tissues and cells. This chapter describes a
pre-embedding electron microscopic method for glycan localization in which tissue
sections and cells are incubated with lectin prior to embedding in resin.
PMID- 27515087
TI - Pre-embedding Nanogold Silver and Gold Intensification.
AB - Pre-embedding nanogold silver and gold intensification methods involve
immunoreactions with nanogold-labeled antibodies and intensification of the
nanogold particles before embedding and ultrathin sectioning. These highly
sensitive methods show good resolution and ultrastructural preservation. They
also are useful for simultaneous observation of immunolabeled cells under light
and electron microscopes, and for three-dimensional immunoelectron microscopic
analyses. Silver intensification is usually superior for immunolabeling. On the
other hand, ultrastructural preservation is better when gold intensification is
used. In this chapter, we introduce pre-embedding nanogold silver and gold
intensification procedures for use primarily with cultured cells.
PMID- 27515088
TI - Post-embedding Mammalian Tissue for Immunoelectron Microscopy: A Standardized
Procedure Based on Heat-Induced Antigen Retrieval.
AB - We describe a standardized method of fixation, antigen retrieval, and image
contrasting for post-embedding immunoelectron microscopy. Tissues are fixed with
formaldehyde solutions containing Ca(2+) and Mg(2+) ions at pH 7.4 and then at pH
8.5. After dehydration with dimethylformamide, the specimens are embedded in LR
White resin. For antigen retrieval, ultrathin sections are heated in 0.5 M Tris
HCl, pH 9.0, for 1-2 h at 95 degrees C. After immunogold labeling, the sections
are treated with a mixture of tannic acid and glutaraldehyde, with OsO4 solution,
and then double-stained with uranyl acetate and lead citrate. The standardized
method yields strong and reproducible immunoreactions for many antigens showing
excellent image contrast without destruction of fine structures.
PMID- 27515089
TI - Pre- and Post-embedding Immunogold Labeling of Tissue Sections.
AB - Despite the improved resolution capacities of fluorescence microscopy over the
last 20 years, localization of specific proteins at the ultrastructural level
with gold-conjugated antibodies remains a valuable technique in the cell
biological tool chest. Ultrastructural immunolocalization of specific proteins in
tissues rather than in cultured cells is often advantageous because, in tissues,
the interactions between different cell types and with the extracellular matrix
are maintained. Here, we describe two immunogold labeling procedures to localize
at the ultrastructural level one or more proteins. In the first procedure (pre
embedding), micrometer-thick tissue cryostat sections are immunostained prior to
embedding for obtaining ultrathin sections suitable for TEM, while in the second
procedure (post-embedding), tissues are embedded in a hydrophobic resin such as
Lowicryl K4M and ultrathin sections are first obtained and then immunolabeled.
While the former method is better at generating strong immunolabeling, the latter
is better at preserving ultrastructure.
PMID- 27515090
TI - Immunogold Labeling for Scanning Electron Microscopy.
AB - Scanning electron microscopes are useful biological tools that can be used to
image the surface of whole organisms, tissues, cells, cellular components, and
macromolecules. Processes and structures that exist at surfaces can be imaged in
pseudo, or real 3D at magnifications ranging from about 10* to 1,000,000*.
Therefore a whole multicellular organism, such as a fly, or a single protein
embedded in one of its cell membranes can be visualized. In order to identify
that protein at high resolution, or to see and quantify its distribution at lower
magnifications, samples can be labeled with antibodies. Any surface that can be
exposed can potentially be studied in this way. Presented here is a generic
method for immunogold labeling for scanning electron microscopy, using two
examples of specimens: isolated nuclear envelopes and the cytoskeleton of
mammalian culture cells. Various parameters for sample preparation, fixation,
immunogold labeling, drying, metal coating, and imaging are discussed so that the
best immunogold scanning electron microscopy results can be obtained from
different types of specimens.
PMID- 27515091
TI - Monitoring Synaptic Vesicle Protein Sorting with Enhanced Horseradish Peroxidase
in the Electron Microscope.
AB - Protein sorting is the fundamental cellular process that creates and maintains
cell organelles and subcellular structures. The synaptic vesicle (SV) is a unique
cell organelle that contains a plethora of specific SV proteins and its protein
composition is crucial for its function. Thus understanding the mechanisms that
sort proteins to SVs and other cell organelles is central to neuroscience and
cell biology.While in the past protein sorting was studied in the fluorescence
and confocal microscope, we here present a protocol that reveals SV protein
trafficking and sorting in the electron microscope (EM). The protocol exploits
tagging SV proteins with a new genetically encoded label for EM: enhanced
horseradish peroxidase (eHRP). eHRP gained its high sensitivity through direct
evolution of its catalytic activity and is detectable in the EM and LM after
expression in neurons and other mammalian cells. The protocol describes the use
of eHRP, labeling of SVs in cultured hippocampal neurons, and analysis via serial
section reconstruction.
PMID- 27515092
TI - Functional Nanoscale Imaging of Synaptic Vesicle Cycling with Superfast Fixation.
AB - Functional imaging is the measurement of structural changes during an ongoing
physiological process over time. In many cases, functional imaging has been
implemented by tracking a fluorescent signal in live imaging sessions. Electron
microscopy, however, excludes live imaging which has hampered functional imaging
approaches on the ultrastructural level. This barrier was broken with the
introduction of superfast fixation. Superfast fixation is capable of stopping and
fixing membrane traffic at sufficient speed to capture a physiological process at
a distinct functional state. Applying superfast fixation at sequential time
points allows tracking of membrane traffic in a step-by-step fashion.This
technique has been applied to track labeled endocytic vesicles at central
synapses as they pass through the synaptic vesicle cycle. At synapses,
neurotransmitter is released from synaptic vesicles (SVs) via fast activity
dependent exocytosis. Exocytosis is coupled to fast endocytosis that retrieves
SVs components from the plasma membrane shortly after release. Fluorescent FM
dyes that bind to the outer leaflet of the plasma membrane enter the endocytic
vesicle during membrane retrieval and remain trapped in endocytic vesicles have
been widely used to study SV exo-endocytic cycling in live imaging sessions. FM
dyes can also be photoconverted into an electron-dense diaminobenzidine polymer
which allows the investigation of SV cycling in the electron microscope. The
combination of FM labeling with superfast fixation made it possible to track the
fine structure of endocytic vesicles at 1 s intervals. Because this combination
is not specialized to SV cycling, many other cellular processes can be studied.
Furthermore, the technique is easy to set up and cost effective.This chapter
describes activity-dependent FM dye labeling of SVs in cultured hippocampal
neurons, superfast microwave-assisted fixation, photoconversion of the
fluorescent endocytic vesicles, and the analysis of individual synapses after
serial section 3D reconstruction of individual synapses from electron
micrographs.
PMID- 27515093
TI - Expression of glycosylated alpha-dystroglycan in newborn skeletal and cardiac
muscles of fukutin related protein (FKRP) mutant mice.
AB - INTRODUCTION: Mutations in the Fukutin related protein (FKRP) gene are
characterized by a lack of functionally glycosylated alpha-dystroglycan (F-alpha
DG) in muscles. A small number of fibers retain the capacity to produce strong
IIH6 reactive glycosylated-alpha-DG (g-alpha-DG) in muscles of both FKRP mutant
animals and patients. METHODS: We examined the expression of g-alpha-DG in limb,
diaphragm, and cardiac muscles of newborn FKRP mutants and LARGEmyd mice with
IIH6 antibody. RESULTS: Near-normal levels of g-alpha-DG were detected in all 3
muscles in the FKRP448LNeo- mutant. Expression was limited within the first 8
postnatal days with decreasing levels. No expression was identified in LARGEmyd
mice. CONCLUSIONS: Temporary expression of glycosylated-alpha-DG in newborn FKRP
mutant muscles is LARGE- and mutant FKRP-dependent. The capability of mutant FKRP
with a severe clinic phenotype to produce glycosylated-alpha-DG provides a new
perspective for possible approaches to mitigate FKRP deficiency. Muscle Nerve 55:
582-590, 2017.
PMID- 27515094
TI - Hoyosella rhizosphaerae sp. nov., a halotolerant actinobacterium isolated from
rhizosphere soil of Suaeda salsa, and emended description of the genus Hoyosella.
AB - A halotolerant actinobacterium, designated J12GA03T, was isolated from a
rhizosphere soil sample of Suaeda salsa collected from a dried saline lake in
Hebei Province, China. Cells were Gram-staining-positive, non-motile and non
spore-forming cocci. Strain J12GA03T grew optimally at 28-37 degrees C, 0-3 %
NaCl (w/v) and pH 6.5-7.5. It contained meso-diaminopimelic acid as the
diagnostic diamino acid and arabinose, galactose and ribose as the diagnostic
whole-cell sugars. MK-8 and MK-7 were detected as predominant menaquinones. Major
fatty acids were C17 : 1omega8c, C16 : 0 and C17 : 0. Polar lipids were
phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol,
phosphatidylglycerol, phosphoglycolipids, glycolipids, unidentified phospholipids
and additional lipids. The muramyl residue was acetyl. Mycolic acids (34-38
carbon atoms) were present. The G+C content of the genomic DNA was 55.8 mol%. It
shared the highest 16S rRNA gene sequence similarities with Amycolicicoccus
subflavus DQS3-9A1T (98.18 %) and Hoyosella altamirensis OFN S31T (97.75 %).
Phylogenetic trees showed that strain J12GA03T firmly formed a distinct
monophyletic branch in the clade with A.subflavus DQS3-9A1T and H.altamirensis
DSM 45258T. The levels of DNA-DNA relatedness with A.subflavus DSM 45089T and
H.altamirensis DSM 45258T were 39.7+/-3.9 % and 35.7+/-3.0 %, respectively.
Combining the evidence from the polyphasic taxonomic study, strain J12GA03T
represents a novel species of the genus Hoyosella, for which the name Hoyosella
rhizosphaerae sp. nov. is proposed. The type strain is J12GA03T (=DSM
101985T=CGMCC 1.15478T).
PMID- 27515095
TI - Which one is more effective for the clinical treatment of chronic pain in knee
osteoarthritis: radiofrequency neurotomy of the genicular nerves or intra
articular injection?
AB - OBJECTIVES: To compare the efficacy of intra-articular injection and
radiofrequency (RF) neurotomy of genicular nerves in patients with chronic knee
osteoarthritis (OA) pain. METHODS: Seventy-three patients with knee OA were
included in the study. Patients were randomly assigned to Group IA (intra
articular 2.5 mL of bupivacaine, 2.5 mg of morphine and 1 mL of betamethasone, 6
mL of fluid injection) or Group RF (RF neurotomy of the genicular nerves). The
outcome measures included a pain scale (visual analog scale, VAS) and Western
Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis. RESULTS: No
statistically significant difference was found between the two groups in baseline
VAS-pain. In Group RF, a significant reduction was observed in VAS-pain at the
first month (P < 0.001) and the third month (P < 0.001) in comparison to Group
IA. Also in Group RF, a significant reduction was observed in WOMAC total scores
in the first month (P < 0.001) in comparison to Group IA. CONCLUSION: This study
is the first controlled study in the literature which compares RF genicular nerve
to intra-articular injections. This study demonstrated that genicular nerve RF
neurotomy is a safe and efficient treatment modality and provides functional
improvement along with an analgesia in patients with chronic knee OA.
PMID- 27515096
TI - Decreased expression of NR4A nuclear receptors in adenomyosis impairs endometrial
decidualization.
AB - STUDY QUESTION: How do NR4A receptors drive decidualization of human endometrial
stromal cells (hESCs)? SUMMARY ANSWER: NR4A receptors modulate endometrial
decidualization by transcriptional activation of FOXO1A, and in adenomyosis
patients, the reduced expression of NR4A receptors in the eutopic endometrium may
represent a novel mechanism to explain impaired decidualization and subfertility.
WHAT IS KNOWN ALREADY: A close relationship between impaired decidualization and
subfertility has been established. In human endometrial stromal cells, orphan
nuclear receptor NR4A is a novel regulator of decidualization. STUDY DESIGN,
SAMPLES/MATERIALS, METHODS: Eutopic endometrial tissues and hESCs from fertile
controls (n = 56) and adenomyosis patients (n = 27) were collected for in vitro
analysis. Primary hESCs isolated from eutopic endometrial tissues were used to
evaluate the biological function of NR4A receptors. Adenovirus-mediated
overexpression of NR4A and small interfering RNAs targeting NR4A, and FOXO1A were
used to investigate the molecular mechanisms. Gene expression regulation was
examined by real-time-quantitative PCR, immunostaining, and luciferase reporter
assay. Artificial decidualization assay was performed to investigate the role of
NR4A1 during decidualization in vivo. MAIN RESULTS AND THE ROLE OF CHANCE: NR4A
modulates the decidualization of hESCs by upregulating prolactin (PRL) and
insulin-like growth factor binding protein-1 (IGFBP-1) expression and
transformation in vitro. Loss of uterine Nr4a1 results in female subfertility due
to impaired decidualization. Mechanistically, NR4A binds to the nerve growth
factor 1B (NGFI-B) -responsive element (NBRE) (-843 to -813) within the FOXO1A
promoter region and regulates FOXO1A expression. Loss of FOXO1A significantly
inhibits PRL and IGFBP-1 expression, as induced by NR4A. Moreover, the expression
of NR4A and FOXO1A was lower in adenomyosis endometrial tissues compared to
fertile controls, especially in stroma compartments. Ectopic NR4A expression
rescued PRL and IGFBP-1 expression in adenomyotic hESCs to near-normal levels.
Furthermore, PI3K/AKT signaling pathway involved in inducing NR4A expression
under decidualization stimuli in hESCs and the level of p(Ser473)-AKT was
significantly higher in stroma in endometrium from patients with adenomyosis.
LIMITATIONS, REASONS FOR CAUTION: This is an in vitro study with a small sample
size, utilizing stromal cell cultures from endometrial tissues of adenomyosis
patients. Furthermore, results obtained should also be confirmed in a larger data
set and with adenomyosis mouse models in vivo. WIDER IMPLICATIONS OF THE
FINDINGS: Identification of a positive agonist of NR4A receptors will be critical
for the improved treatment of patients with conditions of insufficient
decidualization-associated infertility, such as adenomyosis and endometriosis.
LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTERESTS: This study was
supported by the National Natural Science Foundation of China (81170570, G.J.Y.
81370683, G.J.Y. 81501251, Y.J. 31571189, H.X.S. and 81571402, G.J.Y.), and a
special grant for clinical medicine science of Jiangsu Province (BL2014003,
H.X.S.). The authors have no conflicts of interest to declare.
PMID- 27515097
TI - Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to
severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm(r) - and
placebo-controlled trial (BRIDGE).
AB - BACKGROUND: Fumaric acid esters (FAEs) are recommended in international
guidelines for induction and long-term treatment of adults with moderate-to
severe chronic plaque psoriasis. The fixed combination Fumaderm(r) is approved in
Germany, with dimethyl fumarate (DMF) being the main active ingredient.
OBJECTIVES: To assess the efficacy and safety of a new formulation of DMF
(LAS41008), compared with placebo and Fumaderm(r) , in adults with moderate-to
severe chronic plaque psoriasis. METHODS: In this phase III, double-blind,
placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012
000055-13), patients were randomized to receive LAS41008, Fumaderm(r) or placebo
(2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg,
depending upon individual response. The coprimary end points were the percentage
of patients achieving >= 75% improvement in Psoriasis Area and Severity Index
(PASI 75) and the percentage achieving a score of 'clear' or 'almost clear' in
the Physician's Global Assessment (PGA) at week 16. RESULTS: In total, 671
patients were randomized and included in the full analysis set (n = 267,
LAS41008; n = 273, Fumaderm(r) ; n = 131, placebo). At week 16, 37.5% of patients
treated with LAS41008 achieved PASI 75, compared with 15.3% receiving placebo
(superiority for LAS41008 vs. placebo: P < 0.001) and 40.3% receiving Fumaderm(r)
(noninferiority for LAS41008 vs. Fumaderm(r) : P < 0.001). Overall, 33% of
patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week
16, compared with 13.0% receiving placebo (P < 0.0001; LAS41008 superiority vs.
placebo) and 37.4% receiving Fumaderm(r) . Most treatment-related adverse events
were classed as 'mild' in severity. CONCLUSIONS: LAS41008 (DMF) is effective in
the treatment of adults with moderate-to-severe chronic plaque psoriasis.
PMID- 27515099
TI - Identification and functional analysis of invasion associated locus B (IalB) in
Bartonella species.
AB - Bartonellosis is caused by the genus Bartonella. Bartonella is widely distributed
in the ruminants, cats, dogs, rodents and other mammals including humans. At
least 13 species or subspecies of Bartonella are zoonotic, and each species
appears to be highly adapted to one or a limited number of reservoir animals in
which it is asymptomatic, while it can be transmitted to humans in which a
variety of clinical manifestations can be caused. It was reported that Bartonella
henselae infection rate among domestic cats was high in nature, making it one of
the leading, important, and easily neglected zoonotic diseases. The aims of this
study were to identify the expression, localization, immunogenicity and
functional mechanism of Bartonella virulence factor IalB. We found that
recombinant IalB protein could react with the serum from infected reservoir hosts
and anti-IalB polyclonal antibodies could react with different Bartonella species
by western blot analysis. According to these results, we proposed that IalB
protein and anti-IalB antibodies would be good candidates for diagnosis of
Bartonella infection by antigen-based anti-IalB antibodies or antibody-based IalB
antigen capture immunoassay, respectively. We also found that IalB had a putative
22-amino-acid signal sequence and little IalB was localized to the outer membrane
of Bartonella birtlesii by electron microscopy assay. Incubation with anti-IalB
polyclonal antibodies resulted in inhibition of the invasion of mouse
erythrocytes by B. birtlesii. According to these results, we propose that IalB
could be a secreted protein that facilitates Bartonella entry into erythrocytes.
In conclusion, these results improve our understanding of IalB as a candidate for
immunodiagnosis and how IalB affects Bartonella-erythrocyte entry.
PMID- 27515098
TI - Atlantic salmon populations reveal adaptive divergence of immune related genes -
a duplicated genome under selection.
AB - BACKGROUND: Populations of Atlantic salmon display highly significant genetic
differences with unresolved molecular basis. These differences may result from
separate postglacial colonization patterns, diversifying natural selection and
adaptation, or a combination. Adaptation could be influenced or even facilitated
by the recent whole genome duplication in the salmonid lineage which resulted in
a partly tetraploid species with duplicated genes and regions. RESULTS: In order
to elucidate the genes and genomic regions underlying the genetic differences, we
conducted a genome wide association study using whole genome resequencing data
from eight populations from Northern and Southern Norway. From a total of ~4.5
million sequencing-derived SNPs, more than 10 % showed significant
differentiation between populations from these two regions and ten selective
sweeps on chromosomes 5, 10, 11, 13-15, 21, 24 and 25 were identified. These
comprised 59 genes, of which 15 had one or more differentiated missense mutation.
Our analysis showed that most sweeps have paralogous regions in the partially
tetraploid genome, each lacking the high number of significant SNPs found in the
sweeps. The most significant sweep was found on Chr 25 and carried several
missense mutations in the antiviral mx genes, suggesting that these populations
have experienced differing viral pressures. Interestingly the second most
significant sweep, found on Chr 5, contains two genes involved in the NF-KB
pathway (nkap and nkrf), which is also a known pathogen target that controls a
large number of processes in animals. CONCLUSION: Our results show that natural
selection acting on immune related genes has contributed to genetic divergence
between salmon populations in Norway. The differences between populations may
have been facilitated by the plasticity of the salmon genome. The observed
signatures of selection in duplicated genomic regions suggest that the recently
duplicated genome has provided raw material for evolutionary adaptation.
PMID- 27515101
TI - Hepatitis C virus plays hide and seek with neutralizing antibodies.
PMID- 27515100
TI - Long-term prognostic value of risk scores after drug-eluting stent implantation
for unprotected left main coronary artery: A pooled analysis of the ISAR-LEFT
MAIN and ISAR-LEFT-MAIN 2 randomized clinical trials.
AB - OBJECTIVES: To evaluate the long-term prognostic value of risk scores in the
setting of drug-eluting stent (DES) implantation for uLMCA. BACKGROUND: Data on
the prognostic value of novel risk scores developed to select the most
appropriate revascularization strategy in patients undergoing DES implantation
for uLMCA disease are relatively limited. METHODS: The study represents a patient
level pooled analysis of the ISAR-LEFT-MAIN (607 patients randomized to
paclitaxel-eluting or sirolimus-eluting stents) and the ISAR-LEFT-MAIN-2 (650
patients randomized to everolimus-eluting or zotarolimus-eluting stents)
randomized trials. The Syntax Score (SxScore) as well the Syntax Score II (SS
II), the EuroSCORE and the Global Risk Classification (GRC) were calculated. The
primary outcome was all-cause mortality. RESULTS: At a mean follow-up of 3 years
there were 160 deaths (12.7%). The death-incidence was significantly higher in
the upper tertiles than in the intermediate or lower ones for all risk scores
(log-rank test P < 0.01 for all comparisons). The discriminatory power of a
multivariable model for prediction of 3-year mortality was significantly improved
after the inclusion of EuroSCORE (adjusted area under the receiver operating
characteristic (ROC) curve = 0.779, 95% confidence interval 0.747 to 0.810, P =
0.008), but not after the inclusion of SxScore, SS II, or GRC. CONCLUSIONS: In
patients undergoing DES implantation for uLMCA disease, all evaluated risk scores
were able to stratify the mortality risk at long-term follow-up. EuroSCORE was
the only risk score that significantly improved the discriminatory power of a
multivariable model to predict long-term mortality. (c) 2016 Wiley Periodicals,
Inc.
PMID- 27515103
TI - Type 1 diabetes mellitus and atrial function: A complex relationship.
PMID- 27515102
TI - Cost of heart failure management in Turkey: results of a Delphi Panel.
AB - OBJECTIVE: To analyze health-related cost of heart failure (HF) and to evaluate
health-related source utilization aiming to provide data on the economic burden
of HF in actual clinical practice in Turkey. METHODS: The study used the Delphi
process of seeking expert consensus of opinion including 11 cardiologists who are
experienced in HF. The standardized questionnaire comprised items to reflect the
opinion of the expert panelists on the distribution of the HF patients in terms
of demographic and clinical characteristics and background disease states. Costs
related to out-patient follow-up, in-patient follow-up, medications, and other
therapies were also evaluated. RESULTS: 34.1% of the HF patients were in the age
range of 60-69 years, and 62.3% were males. Coronary heart disease was the
leading cause of HF (59.6%); 63.6% of the HF patients had reduced ejection
fraction (rEF) and 42.3% were in New York Heart Association (NYHA)-II class.
Approximately 75 % of the patients were followed up by a cardiology unit. The
total annual visit number was estimated as 3.41. Approximately 32% of HF patients
were hospitalized 1.64 times a year, for an average of 6.77 days each time. The
total annual costs of all HF patients and HF-rEF patients were estimated as 1.537
TL and as 2.141 TL, respectively. CONCLUSION: The analysis demonstrating the
magnitude of the economic impact of HF management on Turkey's healthcare system
may help facilitate health and social policy interventions to improve the
prevention and treatment of HF.
PMID- 27515104
TI - Fragmented QRS frequency in patients with cardiac syndrome X.
PMID- 27515105
TI - F-18 FDG PET/CT images of a rare primer cardiac tumour: Primary Pericardial
Mesothelioma.
PMID- 27515106
TI - An extremely rare but possible complication of MitraClip: embolization of clip
during follow-up.
PMID- 27515107
TI - Relation between epicardial fat thickness and chronic obstructive pulmonary
disease.
PMID- 27515108
TI - Author's Reply.